PMID- 25844238
TI  - Crystal structure of 1-butyl-2,3-di-methyl-imidazolium dicarba-7,8-nido-undeca
      borate.
AB  - In the title mol-ecular salt, C9H17N2 (+).C2H12B9 (-), the carborane cage has a
      bridging B-H-B bond on the open B3C2 face. The butyl side chain of the cation
      adopts an extended conformation [C-C-C-C = 179.6 (1) degrees ]. In the crystal,
      the imidazolium ring is almost coplanar with the open face of the carborane
      anion. The cations stack in the [010] direction and the dihedral angle between
      the imidazolium rings of adjacent cations is 68.45 (6) degrees . The butyl chains
      extend into the space between carborane anions. 

PMID- 25844239
TI  - Crystal structure of 2-[(3S,4S)-4-(anthracen-9-yl)-1-(4-meth-oxy-phen-yl)-2
      oxoazetidin-3-yl]-2-aza-2H-phenalene-1,3-dione unknown solvate.
AB  - The central beta-lactam ring of the title compound, C36H24N2O4, is almost planar
      (r.m.s. deviation = 0.003 A) and makes dihedral angles of 17.17 (19), 89.76 (17)
      and 78.44 (17) degrees  with the benzene ring, the anthracene ring (r.m.s.
      deviation = 0.003 A) and the 1H-benzo[de]iso-quinoline-1,3(2H)-dione moiety,
      which is nearly planar [maximum deviation = 0.098 (2) A], respectively. The mol
      ecular structure is stabilized by an intra-molecular C-H?N hydrogen bond. In the
      crystal, mol-ecules are linked via C-H?pi and pi-pi stacking inter-actions
      [centroid-centroid distances = 3.5270 (19) and 3.779 (2) A], forming a three
      dimensional structure. A region of disordered electron density, probably
      disordered solvent mol-ecules, was treated with the SQUEEZE procedure in PLATON
      [Spek (2015 ?). Acta Cryst. C71, 9-18], which indicated a solvent cavity of 322
      A(3) containing approximately 91 electrons. Their formula mass and unit-cell
      characteristics were not taken into account during the refinement. 

PMID- 25844240
TI  - Crystal structure of 2-hydroxy-N-(2-hydroxyethyl)-N-{2-hydroxy-3-[(E)-N
      hydroxyethanimidoyl]-5-methylbenzyl}ethanaminium acetate monohydrate.
AB  - The structure of the title hydrated mol-ecular salt, C14H23N2O4 (+).C2H3O2 (
      ).H2O, was determined as part of a wider study on the use of the mol-ecule as a
      polydentate ligand in the synthesis of Mn(III) clusters with magnetic properties.
      The cation features intra-molecular O-H?N and N-H?O hydrogen-bond inter-actions.
      The crystal structure features a range of inter-molecular hydrogen-bonding inter
      actions, principally O-H?O inter-actions between all three species in the
      asymmetric unit. An R (2) 4(8) graph-set hydrogen-bonding motif between the anion
      and water mol-ecules serves as a unit which links to the cation via the di-ethano
      lamine group. Each O atom of the acetate anion accepts two hydrogen bonds. 

PMID- 25844241
TI  - Crystal structure of methyl (E)-2-(1-methyl-2-oxoindolin-3-yl-idene)acetate.
AB  - The title compound, C12H11NO3, is essentially planar, with the mean plane of the
      acetate side chain [-C-C(=O)-O-C] being inclined to the mean plane of the indole
      ring system by 12.49 (7) degrees . The five- and six-membered rings of the indole
      group are almost coplanar, making a dihedral angle of 1.76 (8) degrees . The
      conformation about the C=C bond is E and there is an intra-molecular C-H?O
      hydrogen bond present. In the crystal, mol-ecules are linked by pairs of C-H?O
      hydrogen bonds forming inversion dimers, with an R 2 (2)(16) ring motif. The
      dimers are linked by a second pair of C-H?O hydrogen bonds, enclosing R 2 (2)(16)
      ring motifs, forming ribbons lying parallel to (-114). The ribbons are linked via
      C-H?pi inter-actions, forming a three-dimensional structure. 

PMID- 25844242
TI  - Crystal structure of 2-{[(naphthalen-1-yl)oxy]meth-yl}-5-(2,4,5-tri-fluoro-phen
      yl)-1,3,4-oxa-diazole.
AB  - In the title compound C19H11F3N2O2, the oxa-diazole ring and the naphthalene ring
      system are approximately planar (r.m.s. deviations of 0.001 and 0.020 A,
      respectively) and the oxa-diazole ring makes dihedral angles of 13.11 (1) and
      7.59 (1) degrees  with the naphthalene ring system and the tri-fluoro-phenyl
      ring, respectively. In the crystal, C-H?N hydrogen bonds link mol-ecules into
      chains along the a-axis direction, while C-H?F contacts form additional chains
      along the ac diagonal. These contacts generate sheets of mol-ecules approximately
      parallel to the (011) plane. 

PMID- 25844243
TI  - Crystal structure of 5,7-diphenyl-4,7-di-hydro-tetra-zolo[1,5-a]pyrimidine.
AB  - In the title mol-ecule, C16H13N5, the plane of the tetra-zole ring forms dihedral
      angles of 16.37 (7) and 76.59 (7) degrees  with the two phenyl rings. The
      dihedral angle between the phenyl rings is 68.05 (6) degrees . The pyrimidine
      ring is in a flattened boat conformation. In the crystal, mol-ecules are linked
      by pairs of N-H?N hydrogen bonds, forming inversion dimers. 

PMID- 25844244
TI  - Crystal structure of 2-methyl-piperazine-1,4-diium bis-(hydrogen maleate).
AB  - In the title salt, C5H14N2 (2+).2C4H3O4 (-), the asymmetric unit contains two
      independent 2-methyl-piperazinium dications, which comprise a racemic pair, and
      four hydrogen maleate monoanions. In the roughly planar hydrogen maleate anions,
      intra-molecular O-H?O hydrogen bonds generate S(7) rings. In the crystal, the
      four independent anions are linked to the 2-methyl-piperazinium cations through N
      H?O hydrogen bonds, forming two-dimensional layered structures lying parallel to
      (001). 

PMID- 25844245
TI  - Crystal structure of ethyl (2S,2'R)-1'-benzyl-3-oxo-3H-di-spiro-[1-benzo-thio
      phene-2,3'-pyrrolidine-2',11''-indeno[1,2-b]quinoxaline]-4'-carboxyl-ate.
AB  - In the title compound, C35H27N3O3S, the spiro-linked five-membered rings both
      adopt twisted conformations. The pyrrolidine ring makes dihedral angles of 80.5
      (1) and 77.4 (9) degrees  with the benzo-thio-phene ring system and the
      quinoxaline ring system, respectively. The S atom and C=O unit of the benzo-thio
      phene ring system are disordered over two opposite orientations in a 0.768
      (4):0.232 (4) ratio. The atoms of the ethyl side chain are disordered over two
      sets of sites in a 0.680 (16):0.320 (16) ratio. In the crystal, mol-ecules are
      linked by C-H?O, C-H?N and pi-pi inter-actions [shortest centroid-centroid
      distance = 3.4145 (19) A], resulting in a three-dimensional network. 

PMID- 25844246
TI  - Crystal structure of 4,6-di-amino-2-(methyl-sulfan-yl)pyridine-3-carbo-nitrile.
AB  - The title pyrimidine derivative, C7H8N4S, is essentially planar, with a maximum
      deviation of 0.029 (2) A from the mean plane of the non-H atoms. In the crystal,
      mol-ecules are linked by an inter-molecular bifurcated N-H?N hydrogen bond
      between the cyano N atom and the two amino groups, an N-H?N hydrogen bond between
      the two amino groups and a weak C-H?pi inter-action, forming a three-dimensional
      network. 

PMID- 25844247
TI  - Crystal structure of S-hexyl (E)-3-(4-methoxy-benzyl-idene)di-thio-carbazate.
AB  - In the title compound, C15H22N2OS2, the di-thio-carbazate group adopts an EE
      conformation with respect to the C=N bond of the benzyl-idene moiety. The hexyl
      side chain adopts an extended conformation and the C-S-C-C torsion angle is 
      93.36 (13) degrees . In the crystal, inversion dimers linked by pairs of N-H?S
      hydrogen bonds generate R 2 (2)(8) loops. 

PMID- 25844248
TI  - Crystal structure of 1-{1-[2-(phenyl-selan-yl)phen-yl]-1H-1,2,3-triazol-4
      yl}cyclo-hexan-1-ol.
AB  - Two independent mol-ecules, A and B, comprise the asymmetric unit of the title
      compound, C20H21N3OSe. While the benzene ring directly bound to the central
      triazole ring is inclined to the same extent in both mol-ecules [dihedral angles
      = 40.41 (12) (mol-ecule A) and 44.14 (12) degrees  (B)], greater differences are
      apparent in the dihedral angles between the Se-bound rings, i.e. 74.28 (12) (mol
      ecule A) and 89.91 (11) degrees  (B). Close intra-molecular Se?N inter-actions of
      2.9311 (18) (mol-ecule A) and 2.9482 (18) A (B) are noted. In the crystal, supra
      molecular chains along the a axis are formed via O-H?N hydrogen bonding. These
      are connected into layers via C-H?O and C-H?N inter-actions; these stack along
      (01-1) without directional inter-molecular inter-actions between them. 

PMID- 25844249
TI  - Crystal structure of 1-{2-[(2-meth-oxy-phen-yl)selan-yl]phen-yl}-4-phenyl-1H
      1,2,3-triazole.
AB  - In the title compound, C21H17N3OSe, the dihedral angles between the central five
      membered ring and the C- and N-bound rings are 17.89 (10) and 42.35 (10) degrees
      , respectively, indicating the mol-ecule is twisted. The dihedral angle between
      the Se-bound rings is 85.36 (10) degrees . A close intra-molecular Se?O contact
      of 2.8507 (13) A is noted. In the crystal, C-H?O, C-H?N and C-H?pi inter-actions
      lead to the formation of supra-molecular layers parallel to (011); these stack
      with no specific inter-molecular inter-actions between them. 

PMID- 25844250
TI  - Crystal structure of 4-phenyl-1-{2-[(2,4,6-tri-methyl-phen-yl)selan-yl]phen-yl}
      1H-1,2,3-triazole.
AB  - In the title compound, C23H21N3Se, the C-bound phenyl ring is almost coplanar
      with the central five-membered ring [dihedral angle = 2.84 (10) degrees ], but
      the N-bound benzene ring is inclined [dihedral angle = 47.52 (10) degrees ]. The
      dihedral angle between the Se-bound rings is 69.24 (9) degrees . An intra
      molecular Se?N inter-action of 3.0248 (15) A is noted. In the crystal, C-H?pi
      inter-actions connect mol-ecules into double layers that stack along the a axis
      with no directional inter-actions between them. 

PMID- 25844251
TI  - Crystal structure of ethyl 6-methyl-2-oxo-4-(3,4,5-tri-meth-oxy-phen-yl)-1,2,3,4
      tetra-hydro-pyrimidine-5-carboxyl-ate.
AB  - In the title compound, C17H22N2O6, the di-hydro-pyrimidine ring adopts a
      flattened boat conformation. The dihedral angle between the benzene ring and the
      mean plane of the di-hydro-pyrimidine ring is 75.25 (6) degrees . In the crystal,
      mol-ecules are linked via pairs of N-H?O hydrogen bonds, forming inversion dimers
      with an R 2 (2)(8) ring motif which are linked through N-H?O and weak C-H?O
      hydrogen bonds. These, together with pi-pi ring inter-actions [centroid-centroid
      distance = 3.7965 (10) A], give an overall three-dimensional structure. 

PMID- 25844252
TI  - Crystal structure of (E)-2-[1-(1,3-benzodioxol-5-yl)ethyl-idene]-N-ethyl-hydra
      zine-1-carbo-thio-amide.
AB  - In the title compound, C12H15N3O2S, the 1,3-benzdioxole fragment is nearly planar
      [the maximum deviation being 0.0515 (14) A], the N-N-C(=S)-N fragment is also
      nearly planar [the maximum deviation being 0.0480 (10) A], and the dihedral angle
      between their mean planes is 23.49 (10) degrees . In the crystal, mol-ecules are
      linked by pairs of N-H?S hydrogen bonds, forming inversion dimers. The dimers are
      stacked along the a axis with neighbouring columns having the same direction;
      however, the mol-ecules show different orientations leading to a centrosymmetric
      arrangement. In the crystal, the methyl-ene group of the ethyl substituent and
      the terminal methyl H atoms are disordered over two sets of sites and were
      refined using a split model with an occupancy ratio of 0.5:0.5. 

PMID- 25844253
TI  - Crystal structure of 1-meth-oxy-pyrene.
AB  - The title compound, C17H12O, crystallized with three independent mol-ecules (A, B
      and C) in the asymmetric unit. In the crystal, the three independent mol-ecules
      are linked by pi-pi inter-actions [centroid-centroid distances = 3.551 (3)-3.977
      (2) A], which lead to the formation of trimers. Between the trimers there are a
      number of C-H?pi inter-actions generating a laminar arrangement parallel to
      (010). The meth-oxy-methyl group in mol-ecule A is disordered over two sets of
      sites, with an occupancy ratio of 0.56 (9):0.44 (9). 

PMID- 25844254
TI  - Crystal structure of diethyl 2-amino-6-[(thio-phen-3-yl)ethyn-yl]azulene-1,3-di
      carboxyl-ate.
AB  - The title compound, C22H19NO4S, has an almost planar geometry supported by intra
      molecular N-H?O and C-H?O hydrogen bonds. The thio-phene ring is inclined to the
      azulene ring by 4.85 (16) degrees , while the eth-oxy-carbonyl groups are
      inclined to the azulene ring by 7.0 (2) and 5.7 (2) degrees . In the crystal, mol
      ecules are linked by pairs of N-H?O hydrogen bonds, forming inversion dimers with
      an R 2 (2)(12) ring motif. The dimers are linked via C-H?pi inter-actions,
      forming sheets parallel to (10-1). 

PMID- 25844255
TI  - Crystal structure of 2-benzamido-N-(2,2-di-eth-oxy-eth-yl)benzamide.
AB  - In the title compound, C20H24N2O4, both peptide bonds adopt a trans configuration
      with respect to the -N-H and -C=O groups. The dihedral angle between the aromatic
      rings is 53.58 (4) degrees . The mol-ecular conformation is stabilized by an
      intra-molecular N-H?O hydrogen bond. The crystal packing is characterized by
      zigzag chains of N-H?O hydrogen-bonded mol-ecules running along the b-axis
      direction. 

PMID- 25844256
TI  - Crystal structure of the tripeptide N-(benzyl-oxycarbon-yl)glycylglycyl-l
      norvaline.
AB  - The title tripeptide, C17H23N3O6, contains a nonproteinogenic C-terminal amino
      acid residue, norvaline, which is an isomer of the amino acid valine. Norvaline,
      unlike valine, has an unbranched side chain. The mol-ecule has a Gly-Gly segment
      which adopts an extended conformation. The norvaline residue also adopts an
      extended backbone conformation while its side chain has a g (+) t conformation.
      In the crystal lattice, N-H?O and O-H?O hydrogen bonds stabilize the packing. Mol
      ecules translated along the crystallographic a axis associate through an N-H?O
      hydrogen bond. The remaining three hydrogen bonds are between mol-ecules related
      by a 2 1 screw axis. 

PMID- 25844257
TI  - The Mississippi Delta Cardiovascular Health Examination Survey: Study Design and
      Methods.
AB  - Assessment of cardiovascular disease (CVD) morbidity and mortality in subnational
      areas is limited. A model for regional CVD surveillance is needed, particularly
      among vulnerable populations underrepresented in current monitoring systems. The
      Mississippi Delta Cardiovascular Health Examination Survey (CHES) is a population
      based, cross-sectional study on a representative sample of adults living in the
      18-county Mississippi Delta region, a rural, impoverished area with high rates of
      poor health outcomes and marked health disparities. The primary objectives of
      Delta CHES are to (1) determine the prevalence and distribution of CVD and CVD
      risk factors using self-reported and directly measured health metrics and (2) to
      assess environmental perceptions and existing policies that support or deter
      healthy choices. An address-based sampling frame is used for household
      enumeration and participant recruitment and an in-home data collection model is
      used to collect survey data, anthropometric measures, and blood samples from
      participants. Data from all sources will be merged into one analytic dataset and
      sample weights developed to ensure data are representative of the Mississippi
      Delta region adult population. Information gathered will be used to assess the
      burden of CVD and guide the development, implementation, and evaluation of
      cardiovascular health promotion and risk factor control strategies.

PMID- 25844258
TI  - Resurgence of mumps in Korea.
AB  - Routine vaccination against mumps has markedly reduced its incidence. However,
      the incidence of mumps continuously has increased since 2007. In 2013, a large
      mumps epidemic occurred in Korea, and this epidemic is still an ongoing problem.
      This epidemic occurred primarily in school settings and affected vaccinated
      adolescents, predominantly male students. The recent resurgence of mumps is
      caused by multiple factors: suboptimal effectiveness of the current mumps
      vaccines, use of the Rubini strain vaccine, waning immunity in the absence of
      natural boosting due to the marked reduction in the mumps incidence, genotype
      mismatch between the vaccine and circulating mumps virus strains, and
      environmental conditions that foster intense exposures. Containment of mumps
      outbreaks is challenging because the sensitivity of diagnostic tests is low among
      vaccinees and control measures are less efficient because of the inherent nature
      of the mumps virus. Despite the suboptimal vaccine effectiveness in outbreak
      settings, maintaining the high vaccine coverage is an important strategy to
      prevent mumps outbreaks, given that the routine use of mumps vaccines has
      substantially reduced the incidence of mumps and its complications as compared
      with that in the pre-vaccine era. In order to control the current mumps epidemic
      and prevent further outbreaks, we need to better understand the dynamics of mumps
      among vaccinated populations and the changing epidemiology in Korea. Concerted
      efforts should be made to systematically monitor the immunization status of the
      Korean population and to improve diagnosis efficiency. Furthermore, more
      effective mumps vaccines need to be developed in the future. 

PMID- 25844259
TI  - A common immunopathogenesis mechanism for infectious diseases: the protein
      homeostasis-system hypothesis.
AB  - It was once believed that host cell injury in various infectious diseases is
      caused solely by pathogens themselves; however, it is now known that host immune
      reactions to the substances from the infectious agents and/or from the injured
      host cells by infectious insults are also involved. All biological phenomena in
      living organisms, including biochemical, physiological and pathological
      processes, are performed by the proteins that have various sizes and shapes,
      which in turn are controlled by an interacting network within the living
      organisms. The author proposes that this network is controlled by the protein
      homeostasis system (PHS), and that the immune system is one part of the PHS of
      the host. Each immune cell in the host may recognize and respond to substances,
      including pathogenic proteins (PPs) that are toxic to target cells of the host,
      in ways that depend on the size and property of the PPs. Every infectious disease
      has its own set of toxic substances, including PPs, associated with disease
      onset, and the PPs and the corresponding immune cells may be responsible for the
      inflammatory processes that develop in those infectious diseases. 

PMID- 25844260
TI  - In vitro Comparison of Anti-Biofilm Effects against Carbapenem-Resistant
      Acinetobacter baumannii: Imipenem, Colistin, Tigecycline, Rifampicin and
      Combinations.
AB  - BACKGROUND: Multi-drug resistant (MDR) Acinetobacter baumannii has emerged as one
      of the most important nosocomial pathogens. In addition to the diverse resistance
      mechanisms, some A. baumannii strains are known to have biofilm-producing
      capacity, thereby decreasing antibiotic effectiveness. MATERIALS AND METHODS:
      This study was designed to assess biofilm-producing capacity of three different
      MDR A. baumannii strains with diverse resistance mechanisms (OXA-51, IMP-1 and
      VIM-2 type beta-lactamases), and intended to compare the effect of each
      antibiotic regimen (rifampicin, colistin, imipenem, tigecycline, rifampicin
      imipenem and rifampicin-colistin) on mature A. baumannii biofilms using in vitro
      polystyrene plate biofilm assay. RESULTS: Among three MDR A. baumannii strains,
      only VIM-2 strain produced strong biofilm compared to the controls (optical
      density, 8.04 +/- 2.16 vs. 0.49 +/- 0.26). Regarding VIM-2 strains, none of
      imipenem, colistin and rifampicin reduced biofilm formation alone at MIC of each
      antibiotic agent (inhibition of biofilm synthesis, less than 30%). In comparison,
      tigecyclin (0.76 +/- 0.23), imipenem-rifampicin (1.07 +/- 0.31) and colistin
      rifampicin (1.47 +/- 0.54) showed a significant inhibition of biofilm synthesis
      compared to the positive controls at 48 hours after incubation (P<0.01).
      Tigecycline inhibited biofilm formation even at the one fourth level of MIC (1.17
      +/- 0.21). Likewise, both imipenem and colistin were also effective even with the
      reduced concentrations when those were combined with rifampicin. Such biofilm
      inhibiting effects with those antibiotic regimens sustained up to 96 hours after
      incubation. CONCLUSION: Tigecycline, imipenem-rifampicin and colistin-rifampicin
      would be effective for the prevention or reduction of biofilm formation caused by
      A. baumannii strains.

PMID- 25844261
TI  - Characteristics of Metallo-beta-Lactamase-Producing Pseudomonas aeruginosa in
      Korea.
AB  - BACKGROUND: The aim of this study was to investigate the molecular
      epidemiological characteristics of metallo-beta-lactamase (MBL)-producing
      Pseudomonas aeruginosa clinical isolates in Korea. MATERIALS AND METHODS: Three
      hundred and twenty nine P. aeruginosa clinical isolates were collected from 23
      general hospitals in Korea from March to June 2014. Species were identified by
      matrix-assited laser desorption/ionization-time of flight and 16S rRNA
      sequencing. Antimicrobial susceptibility was determined by disk diffusion
      methods. Further, minimum inhibitory concentrations of carbapenems were
      determined by Etest. Polymerase chain reaction and sequencing were performed to
      identify genes encoding MBLs. Multi-locus sequence typing and pulsed-field gel
      electrophoresis were performed to determine epidemiological characteristics of
      MBL-producing P. aeruginosa isolates. RESULTS: Of the 329 isolates, 229 (69.6%)
      were susceptible to the carbapenems tested, including imipenem and meropenem;
      while 100 (30.4%) were non-susceptible to more than one of the carbapenems. Genes
      encoding imipenemase-6 (IMP-6) and Verona imipenemase-2 (VIM-2) MBLs were
      identified in 21 (6.4%) isolates (n = 17 and 4, respectively). All MBL-producing
      isolates showed multi-drug resistant phenotype, and a majority (n = 19) of the
      isolates were identified as sequence type 235 (ST235). The remaining isolates (n
      = 2) were identified as ST309 and ST463. CONCLUSION: P. aeruginosa ST235 might
      play an important role in dissemination of MBL genes in Korea.

PMID- 25844262
TI  - Influenza and Pneumococcal Vaccine Coverage Rates among Patients Admitted to a
      Teaching Hospital in South Korea.
AB  - BACKGROUND: Influenza and pneumococcal vaccinations can reduce morbidity and
      mortality especially in the elderly and patients with chronic medical disease.
      The purpose of this study was to estimate vaccination coverage of these
      populations in a hospital setting. MATERIALS AND METHODS: We conducted a cross
      sectional, descriptive study involving adult patients admitted to a 1,000-bed
      teaching hospital on April 15, 2013. We ascertained the information on whether
      the patient had received influenza vaccination within a year prior to admission
      or pneumococcal vaccination by interviewing each patient. RESULTS: A total of 491
      eligible patients aged >=50 years or with chronic medical illnesses were
      analyzed. The overall vaccination rate for influenza was 57.2%, and that of
      pneumococcus was 17.6% among the vaccine-eligible subjects.
      Influenza/pneumococcal vaccination rates of patients by disease were 62.8%/17.2%
      for diabetes, 53.3%/15.6% for malignancy, 67.6%/23.5% for chronic pulmonary
      disease, 66.7%/15.3% for chronic cardiovascular disease, 68.7%/26.9% for chronic
      renal disease, and 51.2%/18.6% for chronic hepatic disease. Young adult patients
      with chronic medical conditions were consistently less likely to receive
      influenza and pneumococcal vaccines irrespective of the underlying disease.
      CONCLUSION: The influenza and pneumococcal vaccine coverage rates among
      hospitalized patients were low in South Korea. This was especially the case for
      young adult patients with chronic medical illnesses.

PMID- 25844263
TI  - Fatal Breakthrough Mucormycosis in an Acute Myelogenous Leukemia Patient while on
      Posaconazole Prophylaxis.
AB  - Posaconazole is a new oral triazole with broad-spectrum antifungal activity.
      Posaconazole has also shown a significant advantage of preventing invasive fungal
      infection compared to fluconazole or itraconazole in patients with prolonged
      neutropenia. Indeed, posaconazole has been commonly used for antifungal
      prophylaxis in patients undergoing remission induction chemotherapy for acute
      myelogenous leukemia or myelodysplastic syndrome. We experienced a case of fatal
      mucormycosis despite posaconazole prophylaxis. To our knowledge, this is the
      first reported case of fatal breakthrough mucormycosis in a patient receiving
      posaconazole prophylaxis during remission induction chemotherapy in Korea. This
      case demonstrated that breakthrough fungal infection can occurs in patients
      receiving posaconazole prophylaxis because of its limited activity against some
      mucorales. 

PMID- 25844264
TI  - The first imported case infected with chikungunya virus in Korea.
AB  - Chikungunya is caused by an arbovirus transmitted by Aedes mosquito vector. With
      the increase of habitat of mosquito by global warming and frequent international
      travel and interchange, chikungunya reemerged and showed global distribution
      recently. Until now there has not been reported any case infected with
      chikungunya virus in Korea. A 23-year-old man has been the Republic of the
      Philippines for 1 week, and visited our emergency center due to fever and back
      pain. Chikungunya viral infection was diagnosed by specific IgM for chickungunya
      virus by enzyme-linked immunosorbent assayin Korea Centers for Disease Control
      and Prevention. His clinical course was self limited. We introduce the first
      imported case infected with chikungunya virus in Korea. 

PMID- 25844265
TI  - Disseminated gonococcal infection presenting as bacteremia and liver abscesses in
      a healthy adult.
AB  - Herein, we describe a bacteremia caused by Neisseria gonorrhoeae that presented
      as liver abscesses. The patient had no risk factors for disseminated gonococcal
      infection. Periodic fever, skin rashes, and papules were present and the results
      of an abdominal computed tomography scan indicated the presence of small liver
      abscesses. The results of blood culture and 16S rRNA sequencing of the bacterial
      isolates confirmed the presence of N. gonorrhoeae. The patient improved with
      antibiotic therapy. 

PMID- 25844266
TI  - A Case of Paenibacillus pasadenensis Bacteremia in a Patient with Acute
      Respiratory Distress Syndrome after Microsurgical Clipping.
AB  - We report the first case of bacteremia by a novel Paenibacillus species,
      Paenibacillus pasadenensis, from a 55-year-old male patient with acute
      respiratory distress syndrome, following a microsurgical clipping procedure of a
      ruptured intracranial aneurysm. The bacterium was identified using 16S rRNA gene
      sequencing analysis, which was applied because current conventional methods
      employed in the clinical microbiology laboratory proved unsuccessful. Since this
      bacterium was first identified in 2006 and has never been reported elsewhere, we
      believe this report can provide practitioners with useful insight on the
      pathogenicity of this species. 

PMID- 25844267
TI  - Revised adult immunization guideline recommended by the korean society of
      infectious diseases, 2014.

PMID- 25844268
TI  - A multifaceted trophic cascade in a detritus-based system: density-, trait-, or
      processing-chain-mediated effects?
AB  - We investigated three pathways by which predators on an intermediate trophic
      level may produce a trophic cascade in detritus-based systems. Predators may
      increase lower trophic levels (bacteria) by reducing density of bacteriovores, by
      altering behavior of bacteriovores, and by processing living bacteriovores into
      carcasses, feces, and dissolved nutrients that are substrates for bacteria. We
      tested these pathways in laboratory experiments with mosquitoes in water-filled
      containers. Larval Toxorhynchites rutilus prey on larval Aedes triseriatus, which
      feed on bacteria. Using containers stocked with oak leaf infusion as a bacterial
      substrate, we compared bacterial productivity at 7 and 14 days for: prey alone;
      prey with a predator; and prey with predation cues but no predator. Controls
      contained no larvae, either with predation cues or without cues. Predation cues
      in the control treatment increased bacterial abundance at 7 days, but this effect
      waned by 14 days. Aedes triseriatus larvae reduced bacterial abundance
      significantly at 14 days. Predator cues and real predation both eliminated the
      negative effect of A. triseriatus on bacterial abundance. Predation cues reduced
      survivorship of A. triseriatus larvae at 14 days, however this effect was smaller
      than the effect of real predation. We further tested effects of residues from
      predation as cues or as detritus in a second experiment in which A. triseriatus
      were killed at similar rates by: real predators; mechanical damage without the
      predator and carcasses left as detritus; or mechanical damage and carcasses
      removed. No prey larvae were killed in controls. Bacterial productivity was
      greater with real predation than in all other treatments and greater when prey
      larvae were killed or killed and removed, than in controls. Thus we find evidence
      that all three pathways contribute to the trophic cascade from T. rutilus to
      bacteria in tree hole systems.

PMID- 25844269
TI  - HIV/AIDS - Related Knowledge, Attitudes, and Sexual Practices among Migrant Wives
      in Rural Anhui Province, China.
AB  - BACKGROUND: Migrant wives have been increasing in some poor rural regions of
      China and they may bridge HIV transmission across regions. This study aimed to
      assess HIV/AIDS-related knowledge, attitudes and sexual practices among this
      population in rural Anhui Province, China. METHODS: A cross-sectional survey was
      conducted with questionnaire of HIV/AIDS-related knowledge, attitudes, and sexual
      practices between June 2011 and May 2012. A total of 730 migrant wives and 207
      local women were enrolled in this study. Unpaired T-test, Chi-square was utilized
      to compare the difference of HIV/AIDS knowledge, attitudes and sexual practices
      between migrant wives and local women. RESULTS: Around 80% of the migrant wives
      were from Yunnan, Guizhou, or Sichuan Provinces. The main sources of HIV/AIDS
      information were TV/radio, posters, and newspapers/periodicals. HIV/AIDS
      knowledge level among migrant wives was significantly lower than that among local
      women (e.g. 47.1% vs 57.0% (p<0.001) answered "Yes" for the question "Can an
      apparently healthy person be HIV-infected?"), and stigma and prejudice towards
      HIV/AIDS among migrant wives were more common than those among local women (e.g.
      73.2% vs 65.7% (p=0.006) answered "No" for the question "If a shopkeeper or food
      seller had the HIV, would you buy food from them?"). Compared to local women,
      migrant wives were more likely to have ever had sex during menstruation (6.8% vs
      3.4%, p=0.065) and extramarital sex (17.5% vs 10.1%, p=0.01), and were less
      likely to consistently use condoms with their husbands (45.8% vs 57.5%, p<0.001)
      or extramarital sex partners (48.8% vs 58.95, p<0.001). CONCLUSIONS: Migrant
      wives in rural China had a low HIV/AIDS knowledge level and high prevalence of
      stigma and prejudice and risky sexual behaviors. Local HIV/AIDS prevention
      programs should target this neglected population.

PMID- 25844271
TI  - Interparental Boundary Problems, Parent-Adolescent Hostility, and Adolescent
      Parent Hostility: A Family Process Model for Adolescent Aggression Problems.
AB  - This study tests interparental boundary problems (IBPs), parent hostility with
      adolescents, and adolescent hostility with parents within a reciprocal influence
      model and tests each as risk factors for adolescent aggression problems.
      Prospective, longitudinal analyses were conducted with multi-informant data from
      768 adolescents and their families, from 6th to 9th grade. Guided by spillover
      and social learning perspectives, our findings suggest that IBPs have a robust,
      negative influence on both parent and adolescent hostility. In turn, adolescent
      hostility was the best predictor of global adolescent aggression problems. Two
      indirect effects were found that link IBPs and adolescent aggression problems;
      however, findings indicate that adolescent hostile behavior in the family is the
      key risk indicator for adolescents' later aggression problems. Model invariance
      tests revealed that this model was not different for boys and girls, or for
      adolescents in families with two biological parents and youth in families with
      two caregivers (e.g. stepparent families).

PMID- 25844270
TI  - Kaempferol Exhibits Progestogenic Effects in Ovariectomized Rats.
AB  - OBJECTIVE: Progesterone (P4) plays a central role in women's health. Synthetic
      progestins are used clinically in hormone replacement therapy (HRT), oral
      contraceptives, and for the treatment of endometriosis and infertility.
      Unfortunately, synthetic progestins are associated with side effects, including
      cardiovascular disease and breast cancer. Botanical dietary supplements are
      widely consumed for the alleviation of a variety of gynecological issues, but
      very few studies have characterized natural compounds in terms of their ability
      to bind to and activate progesterone receptors (PR). Kaempferol is a flavonoid
      that functions as a non-steroidal selective progesterone receptor modulator
      (SPRM) in vitro. This study investigated the molecular and physiological effects
      of kaempferol in the ovariectomized rat uteri. METHODS: Since genistein is a
      phytoestrogen that was previously demonstrated to increase uterine weight and
      proliferation, the ability of kaempferol to block genistein action in the uterus
      was investigated. Analyses of proliferation, steroid receptor expression, and
      induction of well-established PR-regulated targets Areg and Hand2 were completed
      using histological analysis and qPCR gene induction experiments. In addition,
      kaempferol in silico binding analysis was completed for PR. The activation of
      estrogen and androgen receptor signalling was determined in vitro. RESULTS:
      Molecular docking analysis confirmed that kaempferol adopts poses that are
      consistent with occupying the ligand-binding pocket of PRA. Kaempferol induced
      expression of PR regulated transcriptional targets in the ovariectomized rat
      uteri, including Hand2 and Areg. Consistent with progesterone-l ke activity,
      kaempferol attenuated genistein-induced uterine luminal epithelial proliferation
      without increasing uterine weight. Kaempferol signalled without down regulating
      PR expression in vitro and in vivo and without activating estrogen and androgen
      receptors. CONCLUSION: Taken together, these data suggest that kaempferol is a
      unique natural PR modulator that activates PR signaling in vitro and in vivo
      without triggering PR degradation.

PMID- 25844272
TI  - Carbohydrate-Based Polymers for Immune Modulation.
AB  - Carbohydrates play prominent roles in immune surveillance and response to
      infection. Multivalency, molecular weight control, and molecular architecture
      control are properties that polymer science is well suited to address. Each of
      these properties has been demonstrated to impact the biological interaction of
      carbohydrate-bearing chains with their binding partners. This viewpoint
      highlights synthetic advances and potential applications of carbohydrate-based
      polymers for immune modulation. It also offers future directions in polymer
      science necessary for carbohydrate polymers to fulfill their potential as immune
      modulators.

PMID- 25844273
TI  - Gene-diet interactions and their impact on colorectal cancer risk.
AB  - A number of studies have evaluated the role of gene-diet interaction in the
      etiology of colorectal cancer (CRC). Historically, these studies focused on
      established dietary risk factors and genes involved in their metabolism. However,
      results from these candidate gene studies were inconsistent, possibly due to
      multiple testing and publication bias. In recent years, genome-wide association
      studies have identified a number of CRC susceptibility loci, and subsequent meta
      analyses have observed limited evidence that diet may modify the risk associated
      with these susceptibility loci. Statistical techniques have been recently
      developed to evaluate the presence of interaction across the entire genome;
      results from these genome-wide studies have demonstrated limited evidence of
      interaction and have failed to replicate results from candidate gene studies and
      those using established susceptibility loci. However, larger sample sizes are
      likely needed to elucidate modest or weak interaction in genome-wide studies of
      gene-diet interaction.

PMID- 25844274
TI  - Retroviral DNA Transposition: Themes and Variations.
AB  - Retroviruses and LTR retrotransposons are transposable elements that encapsidate
      the RNAs that are intermediates in the transposition of DNA copies of their
      genomes (proviruses), from one cell (or one locus) to another. Mechanistic
      similarities in DNA transposase enzymes and retroviral/retrotransposon integrases
      underscore the close evolutionary relationship among these elements. The
      retroviruses are very ancient infectious agents, presumed to have evolved from
      Ty3/Gypsy LTR retrotransposons (1), and DNA copies of their sequences can be
      found embedded in the genomes of most, if not all, members of the tree of life.
      All retroviruses share a specific gene arrangement and similar replication
      strategies. However, given their ancestries and occupation of diverse
      evolutionary niches, it should not be surprising that unique sequences have been
      acquired in some retroviral genomes and that the details of the mechanism by
      which their transposition is accomplished can vary. While every step in the
      retrovirus lifecycle is, in some sense, relevant to transposition, this Chapter
      focuses mainly on the early phase of retroviral replication, during which viral
      DNA is synthesized and integrated into its host genome. Some of the initial
      studies that set the stage for current understanding are highlighted, as well as
      more recent findings obtained through use of an ever-expanding technological
      toolbox including genomics, proteomics, and siRNA screening. Persistence in the
      area of structural biology has provided new insight into conserved mechanisms as
      well as variations in detail among retroviruses, which can also be instructive.

PMID- 25844277
TI  - The formation of a large summertime Saharan dust plume: Convective and synoptic
      scale analysis.
AB  - Haboobs are dust storms produced by the spreading of evaporatively cooled air
      from thunderstorms over dusty surfaces and are a major dust uplift process in the
      Sahara. In this study observations, reanalysis, and a high-resolution simulation
      using the Weather Research and Forecasting model are used to analyze the
      multiscale dynamics which produced a long-lived (over 2 days) Saharan mesoscale
      convective system (MCS) and an unusually large haboob in June 2010. An upper
      level trough and wave on the subtropical jet 5 days prior to MCS initiation
      produce a precipitating tropical cloud plume associated with a disruption of the
      Saharan heat low and moistening of the central Sahara. The restrengthening
      Saharan heat low and a Mediterranean cold surge produce a convergent region over
      the Hoggar and Air Mountains, where small convective systems help further
      increase boundary layer moisture. Emerging from this region the MCS has
      intermittent triggering of new cells, but later favorable deep layer shear
      produces a mesoscale convective complex. The unusually large size of the
      resulting dust plume (over 1000 km long) is linked to the longevity and vigor of
      the MCS, an enhanced pressure gradient due to lee cyclogenesis near the Atlas
      Mountains, and shallow precipitating clouds along the northern edge of the cold
      pool. Dust uplift processes identified are (1) strong winds near the cold pool
      front, (2) enhanced nocturnal low-level jet within the aged cold pool, and (3) a
      bore formed by the cold pool front on the nocturnal boundary layer.

PMID- 25844276
TI  - Systematic, theoretically-grounded development and feasibility testing of an
      innovative, preventive web-based game for children exposed to acute trauma.
AB  - BACKGROUND: Millions of children are affected by acute medical events annually,
      creating need for resources to promote recovery. While web-based interventions
      promise wide reach and low cost for users, development can be time- and cost
      intensive. A systematic approach to intervention development can help to minimize
      costs and increase likelihood of effectiveness. Using a systematic approach, our
      team integrated evidence on the etiology of traumatic stress, an explicit program
      theory, and a user-centered design process to intervention development.
      OBJECTIVE: To describe evidence and the program theory model applied to the
      Coping Coach intervention and present pilot data evaluating intervention
      feasibility and acceptability. METHOD: Informed by empirical evidence on
      traumatic stress prevention, an overarching program theory model was articulated
      to delineate pathways from a) specific intervention content to b) program targets
      and proximal outcomes to c) key longer-term health outcomes. Systematic user
      testing with children ages 8-12 (N = 42) exposed to an acute medical event and
      their parents was conducted throughout intervention development. RESULTS:
      Functionality challenges in early prototypes necessitated revisions. Child
      engagement was positive throughout revisions to the Coping Coach intervention.
      Final pilot-testing demonstrated promising feasibility and high user-engagement
      and satisfaction. CONCLUSION: Applying a systematic approach to the development
      of Coping Coach led to the creation of a functional intervention that is accepted
      by children and parents. Development of new e-health interventions may benefit
      from a similar approach. Future research should evaluate the efficacy of Coping
      Coach in achieving targeted outcomes of reduced trauma symptoms and improved
      health-related quality of life.

PMID- 25844275
TI  - Site-specific DNA Inversion by Serine Recombinases.
AB  - Reversible site-specific DNA inversion reactions are widely distributed in
      bacteria and their viruses. They control a range of biological reactions that
      most often involve alterations of molecules on the surface of cells or phage.
      These programmed DNA rearrangements usually occur at a low frequency, thereby
      preadapting a small subset of the population to a change in environmental
      conditions, or in the case of phages, an expanded host range. A dedicated
      recombinase, sometimes with the aid of additional regulatory or DNA architectural
      proteins, catalyzes the inversion of DNA. RecA or other components of the general
      recombination-repair machinery are not involved. This chapter discusses site
      specific DNA inversion reactions mediated by the serine recombinase family of
      enzymes and focuses on the extensively studied serine DNA invertases that are
      stringently controlled by the Fis-bound enhancer regulatory system. The first
      section summarizes biological features and general properties of inversion
      reactions by the Fis/enhancer-dependent serine invertases and the recently
      described serine DNA invertases in Bacteroides. Mechanistic studies of reactions
      catalyzed by the Hin and Gin invertases are then discussed in more depth,
      particularly with regards to recent advances in our understanding of the function
      of the Fis/enhancer regulatory system, the assembly of the active recombination
      complex (invertasome) containing the Fis/enhancer, and the process of DNA strand
      exchange by rotation of synapsed subunit pairs within the invertasome. The role
      of DNA topological forces that function in concert with the Fis/enhancer
      controlling element in specifying the overwhelming bias for DNA inversion over
      deletion and intermolecular recombination is emphasized.

PMID- 25844278
TI  - Probabilistic detection of volcanic ash using a Bayesian approach.
AB  - : Airborne volcanic ash can pose a hazard to aviation, agriculture, and both
      human and animal health. It is therefore important that ash clouds are monitored
      both day and night, even when they travel far from their source. Infrared
      satellite data provide perhaps the only means of doing this, and since the hugely
      expensive ash crisis that followed the 2010 Eyjafjalljokull eruption, much
      research has been carried out into techniques for discriminating ash in such data
      and for deriving key properties. Such techniques are generally specific to data
      from particular sensors, and most approaches result in a binary classification of
      pixels into "ash" and "ash free" classes with no indication of the classification
      certainty for individual pixels. Furthermore, almost all operational methods rely
      on expert-set thresholds to determine what constitutes "ash" and can therefore be
      criticized for being subjective and dependent on expertise that may not remain
      with an institution. Very few existing methods exploit available contemporaneous
      atmospheric data to inform the detection, despite the sensitivity of most
      techniques to atmospheric parameters. The Bayesian method proposed here does
      exploit such data and gives a probabilistic, physically based classification. We
      provide an example of the method's implementation for a scene containing both
      land and sea observations, and a large area of desert dust (often misidentified
      as ash by other methods). The technique has already been successfully applied to
      other detection problems in remote sensing, and this work shows that it will be a
      useful and effective tool for ash detection. KEY POINTS: Presentation of a
      probabilistic volcanic ash detection schemeMethod for calculation of probability
      density function for ash observationsDemonstration of a remote sensing technique
      for monitoring volcanic ash hazards.

PMID- 25844279
TI  - The importance of reviewers.

PMID- 25844280
TI  - Microdiskectomy and translaminar approach: minimal invasiveness and flavum
      ligament preservation.
AB  - Study Design Retrospective study. Objective The interlaminar approach represents
      the standard procedure for the surgical treatment of lumbar disk herniation
      (LDH). In the case of disk herniations in the "hidden zone," it could be
      necessary to perform laminotomies or laminectomies and partial or total
      facetectomies to remove the herniated fragment, thus leading to iatrogenic
      instability. The objective of the study is to evaluate the translaminar approach,
      in terms of the results, safety, and efficacy compared with the standard
      approach. Methods Since February 2010, 38 patients (26 men and 12 women; mean age
      50.9 years, range 31 to 78 years) with LDH and migration into the hidden zone
      underwent a microdiskectomy by the translaminar approach. Using a micro-diamond
      dust-coated burr, a translaminar hole (8 +/- 2 mm) was made, with subsequent
      exposure of the involved root and removal of the fragment. A clinical follow-up
      was performed at months 1, 3, 6, and 12 using the visual analog scale and the
      Oswestry Disability Index. All patients were evaluated according to the Spangfort
      score. Postoperative radiographic evaluations were done at 1, 6, and 12 months
      (dynamic radiographic studies done at 6 and 12 months). Results In over 60% of
      cases, L4-L5 was the involved disk. The visualization of the roots was
      successfully achieved through a translaminar approach. No laminotomies,
      laminectomies, or partial or total facetectomies were performed. The flavum
      ligament was always spared. A severe intraoperative bleeding episode occurred in
      5% of the cases, due to involvement of the epidural veins, but it did not result
      in prolonged operative time (mean duration 60 +/- 10 minutes). The patients
      showed a gradual resolution of the back pain and a progressive resolution of the
      radicular pain and the neurologic deficits. No sign of radiographic instability
      was documented during the follow-up. No infections, dural tears, or spinal cord
      injuries occurred. No revision surgery was performed. Conclusion The translaminar
      approach is the only tissue-sparing technique viable in case of cranially
      migrated LDH encroaching on the exiting nerve root in the preforaminal zones, for
      the levels above L2-L3, and in the preforaminal and foraminal zones, for the
      levels below L3-L4 (L5-S1 included, if a total microdiskectomy is not necessary).
      The possibility to spare the flavum ligament is one of the main advantages of
      this technique. According to our experience, the translaminar approach is an
      effective and safe alternative minimally invasive surgical option. 

PMID- 25844281
TI  - Computer-aided surgery does not increase the accuracy of dorsal pedicle screw
      placement in the thoracic and lumbar spine: a retrospective analysis of 2,003
      pedicle screws in a level I trauma center.
AB  - Study Design A retrospective analysis of a prospective database. Objective Meta
      analyses suggest that computer-assisted systems can increase the accuracy of
      pedicle screw placement for dorsal spinal fusion procedures. The results of
      further meta-analyses report that in the thoracic spine, both the methods have
      comparable placement accuracy. These studies are limited due to an abundance of
      screw classification systems. The aim of this study was to assess the placement
      accuracy and potentially influencing factors of three-dimensionally navigated
      versus conventionally inserted pedicle screws. Methods This was a retrospective
      analysis of a prospective database at a level I trauma center of pedicle screw
      placement (computer-navigated versus traditionally placed) for dorsal spinal
      stabilizations. The cases spanned a 5.5-year study period (January 1, 2005, to
      June 30, 2010). The perforations of the pedicle were differentiated in three
      grades based on the postoperative computed tomography. Results The overall
      placement accuracy was 86% in the conventional group versus 79% in the computer
      navigated group (grade 0). The computer-navigated procedures were superior in the
      lumbar spine and the conventional procedures were superior in the thoracic spine,
      but both failed to be of statistical significance. The level of experience of the
      performing surgeon and the patient's body mass index did not influence the
      placement accuracy. The only significant influence was the spinal segment: the
      higher the spinal level where the fusion was performed, the more likely the screw
      was displaced. Conclusions The computer-navigated and conventional methods are
      both safe procedures to place transpedicular screws at the traumatized thoracic
      and lumbar spine. At the moment, three-dimensionally based navigation does not
      significantly increase the placement accuracy. 

PMID- 25844282
TI  - Does Transforaminal Lumbar Interbody Fusion Have Advantages over Posterolateral
      Lumbar Fusion for Degenerative Spondylolisthesis?
AB  - Study Design Retrospective cohort study. Objective To compare the clinical and
      radiographic outcomes of transforaminal lumbar interbody fusion (TLIF) and
      posterolateral lumbar fusion (PLF) in the treatment of degenerative
      spondylolisthesis. Methods This study compared 24 patients undergoing TLIF and 32
      patients undergoing PLF with instrumentation. The clinical outcomes were assessed
      by visual analog scale (VAS) for low back pain and leg pain, physical component
      summary (PCS) of the 12-item Short-Form Health Survey, and the Oswestry
      Disability Index (ODI). Radiographic parameters included slippage of the
      vertebra, local disk lordosis, the anterior and posterior disk height, lumbar
      lordosis, and pelvic parameters. Results The improvement of VAS of leg pain was
      significantly greater in TLIF than in PLF unilaterally (3.4 versus 1.0; p =
      0.02). The improvement of VAS of low back pain was significantly greater in TLIF
      than in PLF (3.8 versus 2.2; p = 0.02). However, there was no significant
      difference in improvement of ODI or PCS between TLIF and PLF. Reduction of
      slippage and the postoperative disk height was significantly greater in TLIF than
      in PLF. There was no significant difference in local disk lordosis, lumbar
      lordosis, or pelvic parameters. The fusion rate was 96% in TLIF and 84% in PLF (p
      = 0.3). There was no significant difference in fusion rate, estimated blood loss,
      adjacent segmental degeneration, or complication rate. Conclusions TLIF was
      superior to PLF in reduction of slippage and restoring disk height and might
      provide better improvement of leg pain. However, the health-related outcomes were
      not significantly different between the two procedures. 

PMID- 25844283
TI  - Transfer of the brachialis to the anterior interosseous nerve as a treatment
      strategy for cervical spinal cord injury: technical note.
AB  - Study Design Technical report. Objective To provide a technical description of
      the transfer of the brachialis to the anterior interosseous nerve (AIN) for the
      treatment of tetraplegia after a cervical spinal cord injury (SCI). Methods In
      this technical report, the authors present a case illustration of an ideal
      surgical candidate for a brachialis-to-AIN transfer: a 21-year-old patient with a
      complete C7 spinal cord injury and failure of any hand motor recovery. The
      authors provide detailed description including images and video showing how to
      perform the brachialis-to-AIN transfer. Results The brachialis nerve and AIN
      fascicles can be successfully isolated using visual inspection and motor mapping.
      Then, careful dissection and microsurgical coaptation can be used for a
      successful anterior interosseous reinnervation. Conclusion The nerve transfer
      techniques for reinnervation have been described predominantly for the treatment
      of brachial plexus injuries. The majority of the nerve transfer techniques have
      focused on the upper brachial plexus or distal nerves of the lower brachial
      plexus. More recently, nerve transfers have reemerged as a potential
      reinnervation strategy for select patients with cervical SCI. The brachialis-to
      AIN transfer technique offers a potential means for restoration of intrinsic hand
      function in patients with SCI. 

PMID- 25844284
TI  - Age-related surgical outcomes of laminoplasty for cervical spondylotic
      myelopathy.
AB  - Study Design Retrospective clinical study. Objective To investigate the age
      related surgical outcomes of laminoplasty. Methods One hundred patients who
      underwent an en bloc laminoplasty for cervical spondylotic myelopathy from 2004
      to 2008 and were followed for at least 1 year were included in this study. The
      clinical outcomes were assessed with the Japanese Orthopaedic Association (JOA)
      score. Acquired points (postoperative JOA score minus preoperative JOA score)
      were also calculated. To investigate the age-related effect for laminoplasty, two
      analyses were conducted: (1) the correlation between age and clinical outcome;
      and (2) the clinical outcomes by decade. Patients were divided into four groups
      according to their age at the time of operation as follows: group 50s, 50 to 59
      years old; group 60s, 60 to 69 years; group 70s, 70 to 79 years; and group 80s,
      80 to 89 years. The pre- and postoperative JOA scores, acquired points,
      preoperative comorbidities, and postoperative complications were then compared
      among the groups. Results Significant correlations were detected between age and
      JOA scores at the preoperative (p = 0.03), postoperative maximum (p < 0.0001),
      and final assessments (p < 0.0001). An age-related decline of JOA scores was
      observed over all periods. The analysis by decades showed the same results. On
      the other hand, the significant differences were not found for acquired points
      over all periods by either method. The preoperative comorbidities of hypertension
      and diabetes mellitus increased with age. Delirium was more common
      postoperatively in elderly patients. Conclusions Although an age-related decline
      of JOA scores was found over all periods, there were no severe sequelae and no
      differences in the acquired points that were age-related. 

PMID- 25844285
TI  - Adverse effect of trauma on neurologic recovery for patients with cervical
      ossification of the posterior longitudinal ligament.
AB  - Study Design Retrospective study. Objective Minor trauma, even from a simple
      fall, can often cause cervical myelopathy, necessitating surgery in elderly
      patients who may be unaware of their posterior longitudinal ligament ossification
      (OPLL). The aim of this study is to determine the influence of trauma on the
      neurologic course in patients who have undergone surgery for cervical OPLL.
      Methods Patients who underwent surgery due to OPLL were divided by trauma history
      and compared (34 in the trauma group; 70 in the nontrauma group). Results Ground
      falls were the most common type of trauma (20 patients, low-energy injuries), but
      23 patients developed new symptoms after a trauma. Although the symptom duration
      (17.68 months) was shorter, the Japanese Orthopedic Association (JOA) score and
      the Nurick scale showed lower values in the trauma group. Trauma histories led
      patients to earlier hospital visits. Initial JOA scores were associated with a
      good recovery status upon the last follow-up in both the groups. The narrowest
      diameter of the spinal canal showed different radiologic parameters: 5.78 mm in
      the trauma group and 6.52 mm in the nontrauma group. Conclusion Minor trauma can
      cause the unexpected development of new symptoms in patients unaware of cervical
      OPLL. Patients with a history of trauma had lower initial JOA scores and showed a
      narrower spinal canal compared with a nontrauma group. The initial JOA scores
      were correlated with a good recovery status upon the last follow-up. 

PMID- 25844286
TI  - Diskectomy during Pregnancy: Case Report and Review of the Literature.
AB  - Study Design Case report. Objective The purpose of this report is to discuss the
      management of a disk herniation during pregnancy and the indication and
      particularities of surgery in this situation. Methods We describe a case of
      diskectomy performed in a 35-year-old woman at 18 weeks of gestation. After 4
      weeks of trying to manage the disk herniation with rest and medications without
      success, the muscle strength of the L5 right root decreased to grade 4, and the
      patient was not responding to intravenous analgesia. After discussion with the
      patient and family, a decision was made to perform the diskectomy. Results After
      surgery, the patient's pain lessened, and the Lasegue test became negative. Two
      weeks after the procedure, the patient's muscle strength was normal. In the 40th
      week of pregnancy, the patient gave birth without any complications. Conclusion
      When necessary, diskectomy can be indicated and performed during pregnancy.
      However, appropriate precautions must be taken. Awareness of these precautions is
      important for the success of the procedure and for the well-being of the mother
      and the newborn. 

PMID- 25844287
TI  - Minimally invasive treatment of a painful osteolytic lumbar lesion secondary to
      epithelioid hemangioendothelioma.
AB  - Study Design Case report. Objective Multifocal epithelioid hemangioendothelioma
      (EHE) of the spine is a rare disorder. We describe a novel, multimodal treatment
      of a painful osteolytic lumbar lesion secondary to EHE. The minimally invasive
      treatment results in an excellent patient outcome with decreased morbidity
      compared to traditional techniques. Methods A previously healthy young adult
      presented with a painful osteolytic lesion at the L2 vertebrae. Imaging revealed
      multifocal spinal lesions consistent with a history of EHE. Core needle biopsy
      confirmed the diagnosis. Preoperative cryoablation of L2 was followed by a staged
      surgery, which included a partial L2 corpectomy, tumor resection, bone grafting,
      and vertebral reconstruction using a minimally invasive technique. This treatment
      was followed by prolonged therapy with interferon and bisphosphonate. Results At
      3.5 years' follow-up, the patient has maintained his vertebral body height, has
      not required a fusion, and has had no recurrence of disease. Conclusion
      Multimodal treatment consisting of tumor cryoablation, partial corpectomy,
      allograft reconstruction of the vertebrae, and adjuvant interferon and
      bisphosphonate can result in good outcomes for well-contained EHE tumors of the
      spine. 

PMID- 25844288
TI  - Corpectomy with adjacent-level kyphoplasty to treat metastatic lung cancer in
      three contiguous cervical vertebrae causing focal neurologic compromise.
AB  - Study Design Case report. Objectives Decompression of metastatic spinal cord
      compression has been shown to improve quality of life and prolong ambulation in
      patients undergoing palliative treatment. We report a case of metastatic cervical
      myelopathy treated with a combined approach using corpectomy and stabilization
      together with balloon kyphoplasty to allow adequate decompression and immediate
      stability in a patient with significant destruction of adjacent vertebral bodies.
      Methods The cervical spine was approached anteriorly and decompressed with a C7
      corpectomy. Subsequent stability was achieved with insertion of a trabecular
      metal cage. Balloon kyphoplasty was used to treat lytic lesions within the
      posterior body of the adjacent vertebrae for pain relief and increased stability.
      Additional stability was achieved through the application of an anterior plate.
      Results Full limited decompression and stabilization were successfully achieved.
      The patient had no further neurologic deterioration and made modest improvements
      that allowed a return to independent ambulation. Conclusion This limited approach
      may be an option for patients with metastatic spinal cord compression, lytic
      destruction of adjacent vertebral bodies, and limited life expectancy. 

PMID- 25844289
TI  - Thoracic Spondylodiscitis Caused by Methicillin-resistant Staphylococcus aureus
      as a Superinfection of Pulmonary Tuberculous Granuloma in an Immunocompetent
      Patient: A Case Report.
AB  - Study Design Case report. Objective To describe a very rare case of an
      immunocompetent man who underwent surgery for thoracic spondylodiscitis caused by
      methicillin-resistant Staphylococcus aureus (MRSA) that developed as a
      superinfection of a pulmonary tuberculous granuloma. Methods Posterior
      decompression and pedicle screw vertebral fixation were followed by T5-T6
      anterior somatotomy with implant of an expandable mesh and lateral plating as
      symptoms worsened. During the anterior approach, an atypical resection of the
      left lower lobe was also performed. Results A tuberculous granuloma was detected
      on histology. Ziehl-Neelsen stain confirmed the diagnosis. Culture also detected
      MRSA. Conclusions Early medical management is the first choice for
      spondylodiscitis to eradicate the infection and alleviate pain. Immobilization of
      the affected spine segments can protect the patient from vertebral collapse and
      from the appearance of neurologic deficits. Surgery is suggested if there are
      compressive effects on the spinal cord, spinal epidural abscess, vertebral
      collapse, and deformity. We decided to remove the abscess and to restore the
      anterior column using an anterior approach. Moreover, in this case, an anterior
      approach allowed us to identify the etiology of the lesion and to determine the
      best chemotherapy regimen. 

PMID- 25844290
TI  - A Meta-Analysis of the Clinical and Fusion Results following Treatment of
      Symptomatic Cervical Pseudarthrosis.
AB  - Study Design Systematic literature review and meta-analysis. Objective This study
      is a meta-analysis assessing the fusion rate and the clinical outcomes of
      cervical pseudarthrosis treated with either a posterior or a revision anterior
      approach. Methods A literature search of PubMed, Cochrane, and Embase was
      performed. Variables of interest included fusion rate and clinical success. The
      effect size based on logit event rate was calculated from the pooled results. The
      studies were weighted by the inverse of the variance, which included both within-
      and between-study error. The confidence intervals were reported at 95%.
      Heterogeneity was assessed using the Q statistic and I (2), where I (2) is the
      estimate of the percentage of error due to between-study variation. Results
      Sixteen studies reported fusion outcomes; 10 studies reported anterior and/or
      posterior results. The pooled fusion success was 86.4% in the anterior group and
      97.1% in the posterior group (p = 0.028). The anterior group demonstrated
      significant heterogeneity with Q value of 34.2 and I (2) value of 73.7%; no
      heterogeneity was seen in the posterior group. The clinical outcomes were
      reported in 10 studies, with eight reporting results of anterior and posterior
      approaches. The pooled clinical success rate was 77.0% for anterior and 71.7% for
      posterior (p = 0.55) approaches. There was significant heterogeneity in both
      groups (I (2) 16.1; 19.2). Conclusions Symptomatic cervical pseudarthrosis can be
      effectively managed with either an anterior or a posterior approach. The
      posterior approach demonstrates a significantly greater fusion rate compared with
      the anterior approach, though the clinical outcome does not differ between the
      two groups. 

PMID- 25844291
TI  - Fundamentals of clinical outcomes assessment for spinal disorders: study designs,
      methodologies, and analyses.
AB  - Study Design A broad narrative review. Objective Management of spinal disorders
      is continuously evolving, with new technologies being constantly developed.
      Regardless, assessment of patient outcomes is key in understanding the safety and
      efficacy of various therapeutic interventions. As such, evidence-based spine care
      is an essential component to the armamentarium of the spine specialist in an
      effort to critically analyze the reported literature and execute studies in an
      effort to improve patient care and change clinical practice. The following
      article, part one of a two-part series, is meant to bring attention to the pros
      and cons of various study designs, their methodological issues, as well as
      statistical considerations. Methods An extensive review of the peer-reviewed
      literature was performed, irrespective of language of publication, addressing
      study designs and their methodologies as well as statistical concepts. Results
      Numerous articles and concepts addressing study designs and their methodological
      considerations as well as statistical analytical concepts have been reported.
      Their applications in the context of spine-related conditions and disorders were
      noted. Conclusion Understanding the fundamental principles of study designs and
      their methodological considerations as well as statistical analyses can further
      advance and improve future spine-related research. 

PMID- 25844292
TI  - Intraoperative Vagus Nerve Monitoring: A Transnasal Technique during Skull Base
      Surgery.
AB  - Objectives Intraoperative vagus nerve monitoring during skull base surgery has
      been reported with the use of an oral nerve monitoring endotracheal tube.
      However, the intraoral presence of an endotracheal tube can limit exposure by its
      location in the operative field during transfacial approaches and by limiting
      superior mobilization of the mandible during transcervical approaches. We
      describe a transnasal vagus nerve monitoring technique. Design and Participants
      Ten patients underwent open skull base surgery. Surgical approaches included
      transcervical (five), transfacial/maxillary swing (three), and double mandibular
      osteotomy (two). The vagus nerve was identified, stimulated, and monitored in all
      cases. Main Outcome Measures Intraoperative nerve stimulation, pre- and
      postoperative vagus nerve function through the use of flexible laryngoscopy in
      conjunction with assessment of subjective symptoms of hoarseness, voice change,
      and swallowing difficulty. Results Three patients had extensive involvement of
      the nerve by tumor with complete postoperative nerve deficit, one patient had a
      transient deficit following dissection of tumor off of nerve with resolution, and
      the remaining patients had nerve preservation. One patient experienced minor
      epistaxis during monitor tube placement that was managed conservatively.
      Conclusions Transnasal vagal nerve monitoring is a simple method that allows for
      intraoperative monitoring during nerve preservation surgery without limiting
      surgical exposure. 

PMID- 25844293
TI  - Technical nuances of autologous pericranium harvesting for dural closure in
      Chiari malformation surgery.
AB  - Duraplasty is a step commonly used for the treatment of Chiari I malformation
      after foramen magnum decompression. A variety of dural substitutes are currently
      available for dural closure to minimize the complications related to
      cerebrospinal fluid (CSF). We describe a technique of harvesting occipital
      pericranium for duraplasty associated with preservation of a wide cuff of muscle
      at the superior nuchal line that allows anatomical muscle closure at the end of
      the procedure. Five symptomatic patients with Chiari I malformation and one
      patient with syringomyelia-Chiari I complex were operated on with this technique.
      The indications to perform a duraplasty were accidental arachnoid breaching in
      three patients during an extra-arachnoidal approach and arachnoidal dissection
      due to intraoperative findings of arachnoid pathology in the remaining three
      patients. The overall morbidity of this technique was nil. In all patients the
      postoperative magnetic resonance imaging scan demonstrated significant expansion
      of the cisterna magna with no evidence of pseudomeningocele. Duraplasty with
      autologous pericranium and standardized closure of soft tissues seem promising in
      reducing the CSF-related complications during Chiari surgery. 

PMID- 25844294
TI  - Incidence and survival patterns of sinonasal undifferentiated carcinoma in the
      United States.
AB  - Objective To determine trends in sinonasal undifferentiated carcinoma (SNUC)
      survival patterns in the United States. Design Retrospective review of national
      database. Participants All cases of SNUC in the National Cancer Institute's
      Surveillance Epidemiology and End Results program from 1973 to 2010 were
      examined. Main Outcome Measures Age-adjusted incidence and survival rates were
      calculated and stratified by demographic information and treatment modality.
      Cohort analysis was performed to analyze survival patterns over time. Results A
      total of 318 SNUC cases were identified. Age-adjusted incidence rate (IR) was
      0.02 per 100,000. Incidence was greater in males (IR: 0.03) than females (IR:
      0.01; p = 0.03). Overall 5- and 10-year relative survival rate was 34.9% and
      31.3%, respectively. Overall median survival was 22.1 months. Median survival
      following surgery combined with radiation was 41.9 months. Five-year relative
      survival rate following surgery, radiation, or surgery combined with radiation
      was 38.7%, 36.0%, and 39.1%, respectively. Median survival from 1973-1986 and
      1987-2010 was 14.5 and 23.5 months, respectively. Conclusions This study provides
      new data regarding survival patterns of SNUC in the United States, confirming
      survival benefit with surgery and radiation as well as identifying a trend toward
      improved survival in recent decades. 

PMID- 25844295
TI  - Early Conquest of the Rock: Julius Lempert's Life and the Complete Apicectomy
      Technique for the Treatment of Suppurative Petrous Apicitis.
AB  - Julius Lempert (1891-1968) was one of the most revolutionary and innovative neuro
      otologists of the 20th century. He had a remarkable role in advancing the field
      of otolaryngology to its modern shape and form, especially through his
      groundbreaking introduction of the fenestration procedure for the treatment of
      otosclerosis. Although he is highly celebrated by many neuro-otologists for his
      contributions to our surgical and anatomical understanding of the petrous bone,
      he is not well known to the neurosurgical community. In this article, we give a
      detailed account of Dr. Lempert's life and discuss his invaluable contribution to
      skull base petrous bone anatomy and surgery through his pioneering work on the
      complete apicectomy for the treatment of suppurative petrous apicitis. 

PMID- 25844296
TI  - Immediate single-stage reconstruction of complex frontofaciobasal injuries: part
      I.
AB  - Objective To determine if immediate (within 6 hours of adequate resuscitation)
      single-stage repair of complex craniofacial injuries could be accomplished with
      acceptable morbidity and mortality taking into consideration the cosmetic
      appearance of the patient. Patients and Methods A total of 26 patients (19 men, 7
      women) ranging in age from 8 to 58 years with Glasgow Coma Scale scores of 5 to
      15 all had a combined single-stage repair of their complex craniofacial injuries
      within 6 hours of their admission. After initial assessment and adequate
      resuscitation, they were evaluated with three-dimensional computed tomography of
      the face and head. Coronal skin flap was used for maximum exposure for frontal
      sinus exenteration as well as dural repair, cortical debridement, calvarial
      reconstruction, and titanium mesh placement. Results Neurosurgical outcome at
      both the early and late evaluations was judged as good in 22 of 26 patients
      (85%), moderate in 3 of 26 (11%), and poor in 1 of the 26 (3.8%). Cosmetic
      surgical outcome at the early evaluation showed 17 of 26 (65%) to be excellent, 4
      of 26 (15.5%) to be good, 4 patients (15.5%) to be fair, and 1 patient (3.8%) to
      be poor. At the late reevaluation, the fair had improved to good with an
      additional reconstructive procedure, and the poor had improved to fair with
      another surgery. There was no calvarial osteomyelitis, graft resorption, or
      intracranial abscess. Complications included three patients (11%): one (3.8%) had
      tension pneumocephaly and meningitis, one (3.8%) had delayed cerebrospinal fluid
      leak with recurrent attacks of meningitis, and one had a maxillary sinus
      infection (3.8%) secondary to front maxillary fistula. Conclusion The immediate
      single-stage repair of complex craniofacial injuries can be performed with
      acceptable results, a decreased need for reoperation, and improved cosmetic and
      functional outcomes. 

PMID- 25844297
TI  - C-shaped Incision for Far-Lateral Suboccipital Approach: Anatomical Study and
      Clinical Correlation.
AB  - Background The standard incision for far-lateral suboccipital approaches has been
      the classic "reverse hockey stick." Although that incision provides ample
      exposure, concern has been raised that excessive muscle dissection and skin
      elevation might lead to accumulation of cerebrospinal fluid (CSF) under the flap
      with increased risk of CSF leak. We hypothesize that the C-shaped incision can
      minimize the amount of muscle dissection and provide optimal exposure and
      surgical outcomes. Objective To describe the anatomical dissection for the C
      shaped incision and clinical application of the C-shaped incision for the far
      lateral approach. Methods A retrospective analysis of all the patients operated
      on at our center using this approach for the treatment of aneurysm of the
      posterior inferior cerebellar artery (PICA) from 2005 to 2011. Results of
      clinical and operative outcome are evaluated. Surgical techniques are described
      in detail. Cadaveric dissections using the C-shaped incision were performed to
      assess the exposure of the far-lateral suboccipital area. Results Eleven
      consecutive patients who had undergone this procedure were selected. All patients
      underwent clipping of PICA aneurysms. Nine patients (82%) presented with ruptured
      aneurysms and subarachnoid hemorrhage. All of them underwent suboccipital
      craniectomy and C1 laminectomy. The dura mater was closed in a watertight fashion
      in 10 patients (91%). No CSF leak or pseudomeningocele were reported. In nine SAH
      patients, two (22%) had postoperative dysphagia and required long-term
      percutaneous endoscopic gastrostomy tube placement. One patient (11%) had chronic
      respiratory failure and required a tracheostomy. Three patients (33%) developed
      hydrocephalus and required a ventriculoperitoneal shunt. Conclusions The C-shaped
      incision is a valid alternative to the classic reverse hockey-stick incision to
      gain exposure for far-lateral craniotomies. Knowing the anatomy and dissection
      techniques can provide an easy and safe route to address anterior lateral cranial
      cervical lesions. Our results suggest the C-shaped incision is reliable in
      preventing CSF leak and the formation of pseudomeningocele. 

PMID- 25844298
TI  - To preserve or not to preserve the orbit in paranasal sinus neoplasms: a meta
      analysis.
AB  - Context The effect on survival of orbital evisceration on patients with paranasal
      sinus neoplasms has not been well established. Objective To review systematically
      the available literature concerning survival in patients who undergo surgery for
      paranasal sinus neoplasm with and without preservation of the eye. Data Source A
      retrospective meta-analysis of English and non-English articles using Medline and
      the Cochrane database. Eligibility Criteria Studies analyzing 5-year survival
      rates in patients who had orbital evisceration compared with orbital preservation
      for the treatment of paranasal sinus neoplasms were included in the final
      analysis. Data Extraction Independent review by two authors using predefined data
      fields. Data Synthesis A meta-analysis of four articles involving 443 patients
      was performed using the DerSimonian-Laird random-effects method. Results Our
      analysis revealed a total effect size of 0.964 in favor of preservation of the
      eye; however, these results are not robust, having a true effect size anywhere
      from 0.785 to 1.142 with a 95% confidence interval. Limitations Only
      retrospective observational studies were included because a prospective
      randomized study cannot be performed in this population. Conclusion Our study
      supports the notion that in select patients preservation of the eye may yield a
      different outcome when compared with orbital evisceration. 

PMID- 25844299
TI  - Junctional Internal Carotid Artery Aneurysms: The Schrodinger's Cat of Vascular
      Neurosurgery.
AB  - Objectives Despite advances in neuroimaging, it is not always definitive whether
      a paraclinoid aneurysm is intradural or entirely extradural. We illustrate the
      potential use of surgical exploration in these aneurysms that we refer to as
      "junctional" aneurysms. Methods Retrospective review of eight patients with
      unruptured aneurysms who underwent a planned surgical exploration of a junctional
      aneurysm. Results Of the eight patients, three underwent exploration of the
      aneurysm during surgery for a different aneurysm. All three of these were found
      to be extradural. Five patients underwent a craniotomy for the exclusive purpose
      of clarifying the location of the aneurysm. Two of these cases were found to be
      intradural and were clipped. Two cases were found to be extradural. In one
      patient, the initially extradural aneurysm was converted into an intradural
      aneurysm during removal of the anterior clinoid process, necessitating surgical
      clipping. One transient third nerve palsy was observed. Discussion Until further
      progress in neuroimaging allows clinicians to determine unequivocally the exact
      anatomical location of a paraclinoid aneurysm, we advocate the use of the term
      junctional aneurysm to reflect the clinical uncertainty inherent in management
      decisions made regarding these aneurysms. We have illustrated a strategy of
      surgical exploration in select patients. 

PMID- 25844300
TI  - Facial Nerve Outcome after Vestibular Schwannoma Resection: A Comparative Meta
      Analysis of Endoscopic versus Open Retrosigmoid Approach.
AB  - The minimal access retrosigmoid endoscopic approach to vestibular schwannoma (VS)
      resection has been used with promising results. However, it has not been compared
      with the standard open approach in the literature. We performed a meta-analysis
      review for all articles describing both approaches for VS from 1996 to 2011. We
      found 1861 articles. After review and discussion, we narrowed our study to 25
      articles, 4 endoscopic and 21 open. The total number of patients was 3026 for
      open and 790 for endoscopic. The mean tumor sizes in the open and endoscopic
      series were 2.5 cm and 2.7 cm, respectively. Good facial nerve outcome was
      achieved in 67% of the open series patients and in 94% of the endoscopic series
      patients. Other outcomes in the open and endoscopic series were the following:
      gross total resection, 91% versus 97%; functional hearing, 22.6% versus 46%;
      wound infection, 1.3% versus 2.6%; and recurrence, 5.4% versus 2.2%. We
      acknowledge the limitations of our study, but we can state that the endoscopic
      approach is not inferior to the standard open approach. In expert hands the
      endoscopic approach can offer as good a result as the open, with potential
      benefits such as less pain and a shorter length of stay in the hospital. There is
      a need for more controlled studies for a definitive comparison. 

PMID- 25844301
TI  - The evolution of endoscopic approaches to the lateral cavernous sinus.

PMID- 25844302
TI  - In reference to "extended inferior turbinate flap for endoscopic reconstruction
      of skull base defects".

PMID- 25844303
TI  - Who will benefit from antidepressants in the acute treatment of bipolar
      depression? A reanalysis of the STEP-BD study by Sachs et al. 2007, using Q
      learning.
AB  - BACKGROUND: There is substantial uncertainty regarding the efficacy of
      antidepressants in the treatment of bipolar disorders. METHODS: Traditional
      randomized controlled trials and statistical methods are not designed to discover
      if, when, and to whom an intervention should be applied; thus, other
      methodological approaches are needed that allow for the practice of personalized,
      evidence-based medicine with patients with bipolar depression. RESULTS: Dynamic
      treatment regimes operationalize clinical decision-making as a sequence of
      decision rules, one per stage of clinical intervention, that map patient
      information to a recommended treatment. Using data from the acute depression
      randomized care (RAD) pathway of the Systematic Treatment Enhancement Program for
      Bipolar Disorder (STEP-BD) study, we estimate an optimal dynamic treatment regime
      via Q-learning. CONCLUSIONS: The estimated optimal treatment regime presents some
      evidence that patients in the RAD pathway of STEP-BD who experienced a
      (hypo)manic episode before the depressive episode may do better to forgo adding
      an antidepressant to a mandatory mood stabilizer.

PMID- 25844304
TI  - Extended Matrix and Inverse Matrix Methods Utilizing Internal Validation Data
      When Both Disease and Exposure Status Are Misclassified.
AB  - The problem of misclassification is common in epidemiological and clinical
      research. In some cases, misclassification may be incurred when measuring both
      exposure and outcome variables. It is well known that validity of analytic
      results (e.g. point and confidence interval estimates for odds ratios of
      interest) can be forfeited when no correction effort is made. Therefore, valid
      and accessible methods with which to deal with these issues remain in high
      demand. Here, we elucidate extensions of well-studied methods in order to
      facilitate misclassification adjustment when a binary outcome and binary exposure
      variable are both subject to misclassification. By formulating generalizations of
      assumptions underlying well-studied "matrix" and "inverse matrix" methods into
      the framework of maximum likelihood, our approach allows the flexible modeling of
      a richer set of misclassification mechanisms when adequate internal validation
      data are available. The value of our extensions and a strong case for the
      internal validation design are demonstrated by means of simulations and analysis
      of bacterial vaginosis and trichomoniasis data from the HIV Epidemiology Research
      Study.

PMID- 25844305
TI  - Sensory Phenomena in Tourette Syndrome: Their Role in Symptom Formation and
      Treatment.
AB  - The primary symptoms of Tourette Syndrome (TS) are motor and vocal tics, but
      increasingly, researchers have examined the role of sensory phenomena in
      biobehavioral models of the disorder. These sensory phenomena involve tic-related
      premonitory urge sensations as well as potential abnormalities in the perceptual
      and behavioral experiences associated with external sensory input. As such,
      dysfunctional sensorimotor integration might represent a key facet of TS
      pathology. The current paper reviews the literature on sensory phenomena in tic
      disorders and highlights possible connections to TS symptoms and directions for
      future research.

PMID- 25844306
TI  - Anatomical likelihood estimation meta-analysis of grey and white matter anomalies
      in autism spectrum disorders.
AB  - Autism spectrum disorders (ASD) are characterized by impairments in social
      communication and restrictive, repetitive behaviors. While behavioral symptoms
      are well-documented, investigations into the neurobiological underpinnings of ASD
      have not resulted in firm biomarkers. Variability in findings across structural
      neuroimaging studies has contributed to difficulty in reliably characterizing the
      brain morphology of individuals with ASD. These inconsistencies may also arise
      from the heterogeneity of ASD, and wider age-range of participants included in
      MRI studies and in previous meta-analyses. To address this, the current study
      used coordinate-based anatomical likelihood estimation (ALE) analysis of 21 voxel
      based morphometry (VBM) studies examining high-functioning individuals with ASD,
      resulting in a meta-analysis of 1055 participants (506 ASD, and 549 typically
      developing individuals). Results consisted of grey, white, and global differences
      in cortical matter between the groups. Modeled anatomical maps consisting of
      concentration, thickness, and volume metrics of grey and white matter revealed
      clusters suggesting age-related decreases in grey and white matter in parietal
      and inferior temporal regions of the brain in ASD, and age-related increases in
      grey matter in frontal and anterior-temporal regions. White matter alterations
      included fiber tracts thought to play key roles in information processing and
      sensory integration. Many current theories of pathobiology ASD suggest that the
      brains of individuals with ASD may have less-functional long-range (anterior-to
      posterior) connections. Our findings of decreased cortical matter in parietal
      temporal and occipital regions, and thickening in frontal cortices in older
      adults with ASD may entail altered cortical anatomy, and neurodevelopmental
      adaptations. 

PMID- 25844307
TI  - Neural correlates of cerebellar-mediated timing during finger tapping in children
      with fetal alcohol spectrum disorders.
AB  - OBJECTIVES: Classical eyeblink conditioning (EBC), an elemental form of learning,
      is among the most sensitive indicators of fetal alcohol spectrum disorders. The
      cerebellum plays a key role in maintaining timed movements with millisecond
      accuracy required for EBC. Functional MRI (fMRI) was used to identify cerebellar
      regions that mediate timing in healthy controls and the degree to which these
      areas are also recruited in children with prenatal alcohol exposure. EXPERIMENTAL
      DESIGN: fMRI data were acquired during an auditory rhythmic/non-rhythmic finger
      tapping task. We present results for 17 children with fetal alcohol syndrome
      (FAS) or partial FAS, 17 heavily exposed (HE) nonsyndromal children and 16 non-
      or minimally exposed controls. PRINCIPAL OBSERVATIONS: Controls showed greater
      cerebellar blood oxygen level dependent (BOLD) activation in right crus I, vermis
      IV-VI, and right lobule VI during rhythmic than non-rhythmic finger tapping. The
      alcohol-exposed children showed smaller activation increases during rhythmic
      tapping in right crus I than the control children and the most severely affected
      children with either FAS or PFAS showed smaller increases in vermis IV-V. Higher
      levels of maternal alcohol intake per occasion during pregnancy were associated
      with reduced activation increases during rhythmic tapping in all four regions
      associated with rhythmic tapping in controls. CONCLUSIONS: The four cerebellar
      areas activated by the controls more during rhythmic than non-rhythmic tapping
      have been implicated in the production of timed responses in several previous
      studies. These data provide evidence linking binge-like drinking during pregnancy
      to poorer function in cerebellar regions involved in timing and somatosensory
      processing needed for complex tasks requiring precise timing.

PMID- 25844308
TI  - The temporal unfolding of face processing in social anxiety disorder--a MEG
      study.
AB  - The current study is the first to use magnetoencephalography (MEG) to examine how
      individuals with social anxiety disorder (SAD) process emotional facial
      expressions (EFEs). We expected that, compared to healthy controls (HCs),
      participants with SAD will show an early (<200 ms post-stimulus) over-activation
      in the insula and the fusiform gyrus (FG, associated with the N170/M170
      component), and later (>200 ms post-stimulus) over-activation in the dorsolateral
      prefrontal cortex (DLPFC). Individuals with SAD (n = 12) and healthy controls
      (HCs, n = 12) were presented with photographs of facial displays during MEG
      recording. As compared to the HC group, the SAD group showed a reduced M170
      (right FG under-activation around 130-200 ms); early reduced activation in the
      right insula, and lower insular sensitivity to the type of EFE displayed. In
      addition, the SAD group showed a late over-activation in the right DLPFC. This
      unique EFE processing pattern in SAD suggests an early under-activation of
      cortical areas, possibly related to reduced emphasis on high spatial frequency
      information and greater early emphasis on low spatial frequency information. The
      late DLPFC over-activation in the SAD group may correlate to failures of
      cognitive control in this disorder. The importance of a temporal perspective for
      the understanding of facial processing in psychopathology is underlined. 

PMID- 25844309
TI  - Regional differences in fiber tractography predict neurodevelopmental outcomes in
      neonates with infantile Krabbe disease.
AB  - BACKGROUND: Krabbe disease is a fatal neurodegenerative disease caused by rapid
      demyelination of the central and peripheral nervous systems. The only available
      treatment, unrelated umbilical cord blood transplantation, is effective only if
      performed before clinical symptoms appear. Phenotypic expressions of disease
      causing mutations vary widely, but genotype-phenotype relationships are unclear.
      Therefore, we evaluated diffusion tensor imaging (DTI) tractography with
      volumetric analysis as a biomarker of early white matter changes and functional
      disability in presymptomatic infants. METHODS: We obtained DTI and structural
      scans of newborns with early-infantile Krabbe disease (n = 9) diagnosed by family
      history or newborn screening. We compared white matter fiber tract properties to
      those of normal controls (n = 336) and assessed the ability of tract-based
      properties to predict longitudinal development in four functional domains
      (cognitive, fine motor, gross motor, adaptive behavior) after treatment with
      unrelated umbilical cord blood transplantation. We also assessed the relationship
      between the standard evaluation (modified Loes score) and DTI results, and the
      volumetric differences between the Krabbe subjects and normal controls. FINDINGS:
      Reductions in fractional anisotropy were significant in the corticospinal tract
      in the Krabbe patients compared to controls, which strongly correlated with motor
      and cognitive outcomes after transplantation. Significant regional differences
      were observed in the splenium and uncinate fasciculus in Krabbe patients and
      these differences correlated only with cognitive outcomes. Regional brain volumes
      of Krabbe patients were slightly larger than controls. Loes scores did not
      correlate with DTI results. INTERPRETATION: Neonatal microstructural
      abnormalities correlate with neurodevelopmental treatment outcomes in patients
      treated for infantile Krabbe disease. DTI with quantitative tractography is an
      excellent biomarker for evaluating infants with Krabbe disease identified through
      newborn screening.

PMID- 25844310
TI  - Age related-changes in the neural basis of self-generation in verbal paired
      associate learning.
AB  - Verbal information is better retained when it is self-generated rather than when
      it is received passively. The application of self-generation procedures has been
      found to improve memory in healthy elderly and in individuals with impaired
      cognition. Overall, the available studies support the notion that active
      participation in verbal encoding engages memory mechanisms that supplement those
      used during passive observation. Thus, the objective of this study was to
      investigate the age-related changes in the neural mechanisms involved in the
      encoding of paired-associates using a self-generation method that has been shown
      to improve memory performance across the lifespan. Subjects were 113 healthy
      right-handed adults (Edinburgh Handedness Inventory >50; 67 females) ages 18-76,
      native speakers of English with no history of neurological or psychiatric
      disorders. Subjects underwent fMRI at 3 T while performing didactic learning
      ("read") or self-generation learning ("generate") of 30 word pairs per condition.
      After fMRI, recognition memory for the second word in each pair was evaluated
      outside of the scanner. On the post-fMRI testing more "generate" words were
      correctly recognized than "read" words (p < 0.001) with older adults recognizing
      the "generated" words less accurately (p < 0.05). Independent component analysis
      of fMRI data identified task-related brain networks. Several components were
      positively correlated with the task reflecting multiple cognitive processes
      involved in self-generated encoding; other components correlated negatively with
      the task, including components of the default-mode network. Overall, memory
      performance on generated words decreased with age, but the benefit from self
      generation remained consistently significant across ages. Independent component
      analysis of the neuroimaging data revealed an extensive set of components engaged
      in self-generation learning compared with didactic learning, and identified areas
      that were associated with age-related changes independent of performance. 

PMID- 25844311
TI  - Multimodal MRI and cognitive function in patients with breast cancer prior to
      adjuvant treatment--the role of fatigue.
AB  - An increasing body of literature indicates that chemotherapy (ChT) for breast
      cancer (BC) is associated with adverse effects on the brain. Recent research
      suggests that cognitive and brain function in patients with BC may already be
      compromised before the start of chemotherapy. This is the first study combining
      neuropsychological testing, patient-reported outcomes, and multimodal magnetic
      resonance imaging (MRI) to examine pretreatment cognition and various aspects of
      brain function and structure in a large sample. Thirty-two patients with BC
      scheduled to receive ChT (pre-ChT+), 33 patients with BC not indicated to undergo
      ChT (pre-ChT-), and 38 no-cancer controls (NCs) were included. The examination
      consisted of a neuropsychological test battery, self-reported aspects of
      psychosocial functioning, and multimodal MRI. Patients with BC reported worse
      scores on several aspects of quality of life, such as higher levels of fatigue
      and stress. However, cortisol levels were not elevated in the patient groups
      compared to the control group. Overall cognitive performance was lower in the pre
      ChT+ and the pre-ChT- groups compared to NC. Further, patients demonstrated
      prefrontal hyperactivation with increasing task difficulty on a planning task
      compared to NC, but not during a memory task. White matter integrity was lower in
      both patient groups. No differences in regional brain volume and brain
      metabolites were found. The cognitive and imaging data converged to show that
      symptoms of fatigue were associated with the observed abnormalities; the observed
      differences were no longer significant when fatigue was accounted for. This study
      suggests that cancer-related psychological or biological processes may adversely
      impact cognitive functioning and associated aspects of brain structure and
      function before the start of adjuvant treatment. Our findings stress the
      importance to further explore the processes underlying the expression of fatigue
      and to study whether it has a contributory role in subsequent treatment-related
      cognitive decline. 

PMID- 25844312
TI  - Multivariate pattern analysis reveals anatomical connectivity differences between
      the left and right mesial temporal lobe epilepsy.
AB  - Previous studies have demonstrated differences of clinical signs and functional
      brain network organizations between the left and right mesial temporal lobe
      epilepsy (mTLE), but the anatomical connectivity differences underlying
      functional variance between the left and right mTLE remain uncharacterized. We
      examined 43 (22 left, 21 right) mTLE patients with hippocampal sclerosis and 39
      healthy controls using diffusion tensor imaging. After the whole-brain anatomical
      networks were constructed for each subject, multivariate pattern analysis was
      applied to classify the left mTLE from the right mTLE and extract the anatomical
      connectivity differences between the left and right mTLE patients. The
      classification results reveal 93.0% accuracy for the left mTLE versus the right
      mTLE, 93.4% accuracy for the left mTLE versus controls and 90.0% accuracy for the
      right mTLE versus controls. Compared with the right mTLE, the left mTLE exhibited
      a different connectivity pattern in the cortical-limbic network and cerebellum.
      The majority of the most discriminating anatomical connections were located
      within or across the cortical-limbic network and cerebellum, thereby indicating
      that these disease-related anatomical network alterations may give rise to a
      portion of the complex of emotional and memory deficit between the left and right
      mTLE. Moreover, the orbitofrontal gyrus, cingulate cortex, hippocampus and
      parahippocampal gyrus, which exhibit high discriminative power in classification,
      may play critical roles in the pathophysiology of mTLE. The current study
      demonstrated that anatomical connectivity differences between the left mTLE and
      the right mTLE may have the potential to serve as a neuroimaging biomarker to
      guide personalized diagnosis of the left and right mTLE. 

PMID- 25844313
TI  - Risk, diagnostic error, and the clinical science of consciousness.
AB  - In recent years, a number of new neuroimaging techniques have detected covert
      awareness in some patients previously thought to be in a vegetative
      state/unresponsive wakefulness syndrome. This raises worries for patients,
      families, and physicians, as it indicates that the existing diagnostic error rate
      in this patient group is higher than assumed. Recent research on a subset of
      these techniques, called active paradigms, suggests that false positive and false
      negative findings may result from applying different statistical methods to
      patient data. Due to the nature of this research, these errors may be
      unavoidable, and may draw into question the use of active paradigms in the
      clinical setting. We argue that false positive and false negative findings carry
      particular moral risks, which may bear on investigators' decisions to use certain
      methods when independent means for estimating their clinical utility are absent.
      We review and critically analyze this methodological problem as it relates to
      both fMRI and EEG active paradigms. We conclude by drawing attention to three
      common clinical scenarios where the risk of diagnostic error may be most
      pronounced in this patient group. 

PMID- 25844314
TI  - T1rho MRI and CSF biomarkers in diagnosis of Alzheimer's disease.
AB  - In the current study, we have evaluated the performance of magnetic resonance
      (MR) T1rho (T1rho) imaging and CSF biomarkers (T-tau, P-tau and Abeta-42) in
      characterization of Alzheimer's disease (AD) patients from mild cognitive
      impairment (MCI) and control subjects. With informed consent, AD (n = 27), MCI (n
      = 17) and control (n = 17) subjects underwent a standardized clinical assessment
      and brain MRI on a 1.5-T clinical-scanner. T1rho images were obtained at four
      different spin-lock pulse duration (10, 20, 30 and 40 ms). T1rho maps were
      generated by pixel-wise fitting of signal intensity as a function of the spin
      lock pulse duration. T1rho values from gray matter (GM) and white matter (WM) of
      medial temporal lobe were calculated. The binary logistic regression using T1rho
      and CSF biomarkers as variables was performed to classify each group. T1rho was
      able to predict 77.3% controls and 40.0% MCI while CSF biomarkers predicted 81.8%
      controls and 46.7% MCI. T1rho and CSF biomarkers in combination predicted 86.4%
      controls and 66.7% MCI. When comparing controls with AD, T1rho predicted 68.2%
      controls and 73.9% AD, while CSF biomarkers predicted 77.3% controls and 78.3%
      for AD. Combination of T1rho and CSF biomarkers improved the prediction rate to
      81.8% for controls and 82.6% for AD. Similarly, on comparing MCI with AD, T1rho
      predicted 35.3% MCI and 81.9% AD, whereas CSF biomarkers predicted 53.3% MCI and
      83.0% AD. Collectively CSF biomarkers and T1rho were able to predict 59.3% MCI
      and 84.6% AD. On receiver operating characteristic analysis T1rho showed higher
      sensitivity while CSF biomarkers showed greater specificity in delineating MCI
      and AD from controls. No significant correlation between T1rho and CSF
      biomarkers, between T1rho and age, and between CSF biomarkers and age was
      observed. The combined use of T1rho and CSF biomarkers have promise to improve
      the early and specific diagnosis of AD. Furthermore, disease progression form MCI
      to AD might be easily tracked using these two parameters in combination. 

PMID- 25844315
TI  - Low-frequency connectivity is associated with mild traumatic brain injury.
AB  - Mild traumatic brain injury (mTBI) occurs from a closed-head impact. Often
      referred to as concussion, about 20% of cases complain of secondary psychological
      sequelae, such as disorders of attention and memory. Known as post-concussive
      symptoms (PCS), these problems can severely disrupt the patient's quality of
      life. Changes in local spectral power, particularly low-frequency amplitude
      increases and/or peak alpha slowing have been reported in mTBI, but large-scale
      connectivity metrics based on inter-regional amplitude correlations relevant for
      integration and segregation in functional brain networks, and their association
      with disorders in cognition and behaviour, remain relatively unexplored. Here, we
      used non-invasive neuroimaging with magnetoencephalography to examine functional
      connectivity in a resting-state protocol in a group with mTBI (n = 20), and a
      control group (n = 21). We observed a trend for atypical slow-wave power changes
      in subcortical, temporal and parietal regions in mTBI, as well as significant
      long-range increases in amplitude envelope correlations among deep-source,
      temporal, and frontal regions in the delta, theta, and alpha bands. Subsequently,
      we conducted an exploratory analysis of patterns of connectivity most associated
      with variability in secondary symptoms of mTBI, including inattention, anxiety,
      and depression. Differential patterns of altered resting state neurophysiological
      network connectivity were found across frequency bands. This indicated that
      multiple network and frequency specific alterations in large scale brain
      connectivity may contribute to overlapping cognitive sequelae in mTBI. In
      conclusion, we show that local spectral power content can be supplemented with
      measures of correlations in amplitude to define general networks that are
      atypical in mTBI, and suggest that certain cognitive difficulties are mediated by
      disturbances in a variety of alterations in network interactions which are
      differentially expressed across canonical neurophysiological frequency ranges. 

PMID- 25844316
TI  - Stochastic process for white matter injury detection in preterm neonates.
AB  - Preterm births are rising in Canada and worldwide. As clinicians strive to
      identify preterm neonates at greatest risk of significant developmental or motor
      problems, accurate predictive tools are required. Infants at highest risk will be
      able to receive early developmental interventions, and will also enable
      clinicians to implement and evaluate new methods to improve outcomes. While
      severe white matter injury (WMI) is associated with adverse developmental
      outcome, more subtle injuries are difficult to identify and the association with
      later impairments remains unknown. Thus, our goal was to develop an automated
      method for detection and visualization of brain abnormalities in MR images
      acquired in very preterm born neonates. We have developed a technique to detect
      WMI in T1-weighted images acquired in 177 very preterm born infants (24-32 weeks
      gestation). Our approach uses a stochastic process that estimates the likelihood
      of intensity variations in nearby pixels; with small variations being more likely
      than large variations. We first detect the boundaries between normal and injured
      regions of the white matter. Following this we use a measure of pixel similarity
      to identify WMI regions. Our algorithm is able to detect WMI in all of the images
      in the ground truth dataset with some false positives in situations where the
      white matter region is not segmented accurately. 

PMID- 25844317
TI  - Cerebellar gray matter and lobular volumes correlate with core autism symptoms.
AB  - Neuroanatomical differences in the cerebellum are among the most consistent
      findings in autism spectrum disorder (ASD), but little is known about the
      relationship between cerebellar dysfunction and core ASD symptoms. The newly
      emerging existence of cerebellar sensorimotor and cognitive subregions provides a
      new framework for interpreting the functional significance of cerebellar findings
      in ASD. Here we use two complementary analyses - whole-brain voxel-based
      morphometry (VBM) and the SUIT cerebellar atlas - to investigate cerebellar
      regional gray matter (GM) and volumetric lobular measurements in 35 children with
      ASD and 35 typically-developing (TD) children (mean age 10.4 +/- 1.6 years; range
      8-13 years). To examine the relationships between cerebellar structure and core
      ASD symptoms, correlations were calculated between scores on the Autism
      Diagnostic Observation Schedule (ADOS) and Autism Diagnostic Interview (ADI) and
      the VBM and volumetric data. Both VBM and the SUIT analyses revealed reduced GM
      in ASD children in cerebellar lobule VII (Crus I/II). The degree of regional and
      lobular gray matter reductions in different cerebellar subregions correlated with
      the severity of symptoms in social interaction, communication, and repetitive
      behaviors. Structural differences and behavioral correlations converged on right
      cerebellar Crus I/II, a region which shows structural and functional connectivity
      with fronto-parietal and default mode networks. These results emphasize the
      importance of the location within the cerebellum to the potential functional
      impact of structural differences in ASD, and suggest that GM differences in
      cerebellar right Crus I/II are associated with the core ASD profile. 

PMID- 25844318
TI  - Functional connectivity modeling of consistent cortico-striatal degeneration in
      Huntington's disease.
AB  - Huntington's disease (HD) is a progressive neurodegenerative disorder
      characterized by a complex neuropsychiatric phenotype. In a recent meta-analysis
      we identified core regions of consistent neurodegeneration in premanifest HD in
      the striatum and middle occipital gyrus (MOG). For early manifest HD convergent
      evidence of atrophy was most prominent in the striatum, motor cortex (M1) and
      inferior frontal junction (IFJ). The aim of the present study was to functionally
      characterize this topography of brain atrophy and to investigate differential
      connectivity patterns formed by consistent cortico-striatal atrophy regions in
      HD. Using areas of striatal and cortical atrophy at different disease stages as
      seeds, we performed task-free resting-state and task-based meta-analytic
      connectivity modeling (MACM). MACM utilizes the large data source of the BrainMap
      database and identifies significant areas of above-chance co-activation with the
      seed-region via the activation-likelihood-estimation approach. In order to
      delineate functional networks formed by cortical as well as striatal atrophy
      regions we computed the conjunction between the co-activation profiles of
      striatal and cortical seeds in the premanifest and manifest stages of HD,
      respectively. Functional characterization of the seeds was obtained using the
      behavioral meta-data of BrainMap. Cortico-striatal atrophy seeds of the
      premanifest stage of HD showed common co-activation with a rather cognitive
      network including the striatum, anterior insula, lateral prefrontal, premotor,
      supplementary motor and parietal regions. A similar but more pronounced co
      activation pattern, additionally including the medial prefrontal cortex and
      thalamic nuclei was found with striatal and IFJ seeds at the manifest HD stage.
      The striatum and M1 were functionally connected mainly to premotor and
      sensorimotor areas, posterior insula, putamen and thalamus. Behavioral
      characterization of the seeds confirmed that experiments activating the MOG or
      IFJ in conjunction with the striatum were associated with cognitive functions,
      while the network formed by M1 and the striatum was driven by motor-related
      tasks. Thus, based on morphological changes in HD, we identified functionally
      distinct cortico-striatal networks resembling a cognitive and motor loop, which
      may be prone to early disruptions in different stages of the disease and underlie
      HD-related cognitive and motor symptom profiles. Our findings provide an
      important link between morphometrically defined seed-regions and corresponding
      functional circuits highlighting the functional and ensuing clinical relevance of
      structural damage in HD. 

PMID- 25844319
TI  - ADHD severity is associated with white matter microstructure in the subgenual
      cingulum.
AB  - AIMS: This analysis examined hypothesised associations between microstructural
      attributes in specific white matter (WM) tracts selected a priori and measures of
      clinical variability in adolescents with a diagnosis of attention deficit
      hyperactivity disorder (ADHD). Firstly, associations were explored between WM
      microstructure and ADHD severity in the subgenual cingulum. Secondly, to ensure
      that tract-specific approaches afforded enhanced rather than differential
      sensitivity, associations were measured between WM microstructure and autistic
      traits in the right corticospinal tract based on results of a previously
      published voxelwise analysis. METHODS: 40 right-handed males aged 14-18 years (19
      with DSM-IV combined type ADHD and 21 healthy controls) underwent a 60 direction
      diffusion MRI scan. Clinical ADHD and autism variation were assessed by validated
      questionnaires. Deterministic tractography based on spherical deconvolution
      methods was used to map the subgenual cingulum and corticospinal tract. RESULTS:
      Fractional anisotropy was positively correlated and radial diffusivity was
      negatively correlated with a) ADHD severity in the left subgenual cingulum and b)
      autistic traits in the inferior segment of the right corticospinal tract. No case
      control differences were found. CONCLUSIONS: Results shed light on possible
      anatomical correlates of ADHD severity and autistic symptoms in pathways which
      may be involved in the ADHD phenotype. They provide further evidence that tract
      specific approaches may a) reveal associations between microstructural metrics
      and indices of phenotypic variability which would not be detected using voxelwise
      approaches, and b) provide improved rather than differential sensitivity compared
      to voxelwise approaches.

PMID- 25844320
TI  - Cardiorespiratory fitness and its association with thalamic, hippocampal, and
      basal ganglia volumes in multiple sclerosis.
AB  - BACKGROUND: There is little known about cardiorespiratory fitness and its
      association with volumes of the thalamus, hippocampus, and basal ganglia in
      multiple sclerosis (MS). Such inquiry is important for identifying a possible
      behavioral approach (e.g., aerobic exercise training) that might change volumes
      of deep gray matter (DGM) structures associated with cognitive and motor
      functions in MS. PURPOSE: This study examined the association between
      cardiorespiratory fitness and volumes of the thalamus, hippocampus, and basal
      ganglia in MS. METHOD: We enrolled 35 persons with MS who underwent a maximal
      exercise test for measuring cardiorespiratory fitness as peak oxygen consumption
      (VO2peak) and brain MRI. Volumes of the thalamus, hippocampus, caudate, putamen,
      and pallidum were calculated from 3D T1-weighted structural brain images. We
      examined associations using partial (pr) correlations controlling for demographic
      and clinical variables. RESULTS: VO2peak was significantly associated with
      composite scaled volumes of the caudate(pr = .47, p < .01), putamen (pr = .44, p
      < .05), pallidum (pr = .40, p < .05), and hippocampus (pr = .42, p < .05), but
      not thalamus (pr = .31, p = .09), when controlling for sex, age, disability, and
      duration of MS. CONCLUSION: Our results provide novel evidence that
      cardiorespiratory fitness is associated with volumes of DGM structures that are
      involved in motor and cognitive functions in MS.

PMID- 25844321
TI  - Fibromyalgia is characterized by altered frontal and cerebellar structural
      covariance brain networks.
AB  - Altered brain morphometry has been widely acknowledged in chronic pain, and
      recent studies have implicated altered network dynamics, as opposed to properties
      of individual brain regions, in supporting persistent pain. Structural covariance
      analysis determines the inter-regional association in morphological metrics, such
      as gray matter volume, and such structural associations may be altered in chronic
      pain. In this study, voxel-based morphometry structural covariance networks were
      compared between fibromyalgia patients (N = 42) and age- and sex-matched pain
      free adults (N = 63). We investigated network topology using spectral
      partitioning, which can delineate local network submodules with consistent
      structural covariance. We also explored white matter connectivity between regions
      comprising these submodules and evaluated the association between probabilistic
      white matter tractography and pain-relevant clinical metrics. Our structural
      covariance network analysis noted more connections within the cerebellum for
      fibromyalgia patients, and more connections in the frontal lobe for healthy
      controls. For fibromyalgia patients, spectral partitioning identified a distinct
      submodule with cerebellar connections to medial prefrontal and temporal and right
      inferior parietal lobes, whose gray matter volume was associated with the
      severity of depression in these patients. Volume for a submodule encompassing
      lateral orbitofrontal, inferior frontal, postcentral, lateral temporal, and
      insular cortices was correlated with evoked pain sensitivity. Additionally, the
      number of white matter fibers between specific submodule regions was also
      associated with measures of evoked pain sensitivity and clinical pain
      interference. Hence, altered gray and white matter morphometry in cerebellar and
      frontal cortical regions may contribute to, or result from, pain-relevant
      dysfunction in chronic pain patients. 

PMID- 25844323
TI  - Predictive value of different conventional and non-conventional MRI-parameters
      for specific domains of cognitive function in multiple sclerosis.
AB  - OBJECTIVE: While many studies correlated cognitive function with changes in brain
      morphology in multiple sclerosis (MS), few of them used a multi-parametric
      approach in a single dataset so far. We thus here assessed the predictive value
      of different conventional and quantitative MRI-parameters both for overall and
      domain-specific cognitive performance in MS patients from a single center.
      METHODS: 69 patients (17 clinically isolated syndrome, 47 relapsing-remitting MS,
      5 secondary-progressive MS) underwent the "Brief Repeatable Battery of
      Neuropsychological Tests" assessing overall cognition, cognitive efficiency and
      memory function as well as MRI at 3 Tesla to obtain T2-lesion load (T2-LL),
      normalized brain volume (global brain volume loss), normalized cortical volume
      (NCV), normalized thalamic volume (NTV), normalized hippocampal volume (NHV),
      normalized caudate nuclei volume (NCNV), basal ganglia R2* values (iron
      deposition) and magnetization transfer ratios (MTRs) for cortex and normal
      appearing brain tissue (NABT). RESULTS: Regression models including clinical,
      demographic variables and MRI-parameters explained 22-27% of variance of overall
      cognition, 17-26% of cognitive efficiency and 22-23% of memory. NCV, T2-LL and
      MTR of NABT were the strongest predictors of overall cognitive function.
      Cognitive efficiency was best predicted by NCV, T2-LL and iron deposition in the
      basal ganglia. NTV was the strongest predictor for memory function and NHV was
      particularly related to memory function. CONCLUSIONS: The predictive value of
      distinct MRI-parameters differs for specific domains of cognitive function, with
      a greater impact of cortical volume, focal and diffuse white matter abnormalities
      on overall cognitive function, an additional role of basal ganglia iron
      deposition on cognitive efficiency, and thalamic and hippocampal volume on memory
      function. This suggests the usefulness of using multiparametric MRI to assess
      (micro)structural correlates of different cognitive constructs.

PMID- 25844322
TI  - Response of the medial temporal lobe network in amnestic mild cognitive
      impairment to therapeutic intervention assessed by fMRI and memory task
      performance.
AB  - Studies of individuals with amnestic mild cognitive impairment (aMCI) have
      detected hyperactivity in the hippocampus during task-related functional magnetic
      resonance imaging (fMRI). Such elevated activation has been localized to the
      hippocampal dentate gyrus/CA3 (DG/CA3) during performance of a task designed to
      detect the computational contributions of those hippocampal circuits to episodic
      memory. The current investigation was conducted to test the hypothesis that
      greater hippocampal activation in aMCI represents a dysfunctional shift in the
      normal computational balance of the DG/CA3 regions, augmenting CA3-driven pattern
      completion at the expense of pattern separation mediated by the dentate gyrus. We
      tested this hypothesis using an intervention based on animal research
      demonstrating a beneficial effect on cognition by reducing excess hippocampal
      neural activity with low doses of the atypical anti-epileptic levetiracetam. In a
      within-subject design we assessed the effects of levetiracetam in three cohorts
      of aMCI participants, each receiving a different dose of levetiracetam. Elevated
      activation in the DG/CA3 region, together with impaired task performance, was
      detected in each aMCI cohort relative to an aged control group. We observed
      significant improvement in memory task performance under drug treatment relative
      to placebo in the aMCI cohorts at the 62.5 and 125 mg BID doses of levetiracetam.
      Drug treatment in those cohorts increased accuracy dependent on pattern
      separation processes and reduced errors attributable to an over-riding effect of
      pattern completion while normalizing fMRI activation in the DG/CA3 and entorhinal
      cortex. Similar to findings in animal studies, higher dosing at 250 mg BID had no
      significant benefit on either task performance or fMRI activation. Consistent
      with predictions based on the computational functions of the DG/CA3 elucidated in
      basic animal research, these data support a dysfunctional encoding mechanism
      detected by fMRI in individuals with aMCI and therapeutic intervention using fMRI
      to detect target engagement in response to treatment. 

PMID- 25844324
TI  - Diffuse alterations in grey and white matter associated with cognitive impairment
      in Shwachman-Diamond syndrome: evidence from a multimodal approach.
AB  - Shwachman-Diamond syndrome is a rare recessive genetic disease caused by
      mutations in SBDS gene, at chromosome 7q11. Phenotypically, the syndrome is
      characterized by exocrine pancreatic insufficiency, bone marrow dysfunction,
      skeletal dysplasia and variable cognitive impairments. Structural brain
      abnormalities (smaller head circumference and decreased brain volume) have also
      been reported. No correlation studies between brain abnormalities and
      neuropsychological features have yet been performed. In this study we investigate
      neuroanatomical findings, neurofunctional pathways and cognitive functioning of
      Shwachman-Diamond syndrome subjects compared with healthy controls. To be
      eligible for inclusion, participants were required to have known SBDS mutations
      on both alleles, no history of cranial trauma or any standard contraindication to
      magnetic resonance imaging. Appropriate tests were used to assess cognitive
      functions. The static images were acquired on a 3 * 0 T magnetic resonance
      scanner and blood oxygen level-dependent functional magnetic resonance imaging
      data were collected both during the execution of the Stroop task and at rest.
      Diffusion tensor imaging was used to assess brain white matter. The Tract-based
      Spatial Statistics package and probabilistic tractography were used to
      characterize white matter pathways. Nine participants (5 males), half of all the
      subjects aged 9-19 years included in the Italian Shwachman-Diamond Syndrome
      Registry, were evaluated and compared with nine healthy subjects, matched for sex
      and age. The patients performed less well than norms and controls on cognitive
      tasks (p = 0.0002). Overall, cortical thickness was greater in the patients, both
      in the left (+10%) and in the right (+15%) hemisphere, significantly differently
      increased in the temporal (left and right, p = 0.04), and right parietal (p =
      0.03) lobes and in Brodmann area 44 (p = 0.04) of the right frontal lobe. The
      greatest increases were observed in the left limbic-anterior cingulate cortex
      (>=43%, p < 0.0004). Only in Broca's area in the left hemisphere did the patients
      show a thinner cortical thickness than that of controls (p = 0.01). Diffusion
      tensor imaging showed large, significant difference increases in both fractional
      anisotropy (+37%, p < 0.0001) and mean diffusivity (+35%, p < 0.005); the Tract
      based Spatial Statistics analysis identified six abnormal clusters of white
      matter fibres in the fronto-callosal, right fronto-external capsulae, left fronto
      parietal, right pontine, temporo-mesial and left anterior-medial-temporal
      regions. Brain areas activated during the Stroop task and those active during the
      resting state, are different, fewer and smaller in patients and correlate with
      worse performance (p = 0.002). Cognitive impairment in Shwachman-Diamond syndrome
      subjects is associated with diffuse brain anomalies in the grey matter (verbal
      skills with BA44 and BA20 in the right hemisphere; perceptual skills with BA5,
      37, 20, 21, 42 in the left hemisphere) and white matter connectivity (verbal
      skills with alterations in the fronto-occipital fasciculus and with the inferior
      longitudinal fasciculus; perceptual skills with the arcuate fasciculus, limbic
      and ponto-cerebellar fasciculus; memory skills with the arcuate fasciculus;
      executive functions with the anterior cingulated and arcuate fasciculus). 

PMID- 25844325
TI  - Developmental changes in large-scale network connectivity in autism.
AB  - BACKGROUND: Disrupted cortical connectivity is thought to underlie the complex
      cognitive and behavior profile observed in individuals with autism spectrum
      disorder (ASD). Previous neuroimaging research has identified patterns of both
      functional hypo- and hyper-connectivity in individuals with ASD. A recent theory
      attempting to reconcile conflicting results in the literature proposes that hyper
      connectivity of brain networks may be more characteristic of young children with
      ASD, while hypo-connectivity may be more prevalent in adolescents and adults with
      the disorder when compared to typical development (TD) (Uddin etal., 2013).
      Previous work has examined only young children, mixed groups of children and
      adolescents, or adult cohorts in separate studies, leaving open the question of
      developmental influences on functional brain connectivity in ASD. METHODS: The
      current study tests this developmental hypothesis by examining within- and
      between-network resting state functional connectivity in a large sample of 26
      children, 28 adolescents, and 18 adults with ASD and age- and IQ-matchedTD
      individuals for the first time using an entirely data-driven approach.
      Independent component analyses (ICA) and dual regression was applied to data from
      three age cohorts to examine the effects of participant age on patterns of within
      networkwhole-brain functional connectivity in individuals with ASD compared with
      TD individuals. Between-network connectivity differences were examined for each
      age cohort by comparing correlations between ICA components across groups.
      RESULTS: We find that in the youngest cohort (age 11 and under), children with
      ASD exhibit hyper-connectivity within large-scale brain networks as well as
      decreased between-network connectivity compared with age-matchedTD children. In
      contrast, adolescents with ASD (age 11-18) do not differ from TD adolescents in
      within-network connectivity, yet show decreased between-network connectivity
      compared with TD adolescents. Adults with ASD show no within- or between-network
      differences in functional network connectivity compared with neurotypical age
      matched individuals. CONCLUSIONS: Characterizing within- and between-network
      functional connectivity in age-stratified cohorts of individuals with ASD and TD
      individuals demonstrates that functional connectivity atypicalities in the
      disorder are not uniform across the lifespan. These results demonstrate how
      explicitly characterizing participant age and adopting a developmental
      perspective can lead to a more nuanced understanding of atypicalities of
      functional brain connectivity in autism.

PMID- 25844327
TI  - Co-localization between the BOLD response and epileptiform discharges recorded by
      simultaneous intracranial EEG-fMRI at 3 T.
AB  - OBJECTIVES: Simultaneous scalp EEG-fMRI can identify hemodynamic changes
      associated with the generation of interictal epileptiform discharges (IEDs), and
      it has the potential of becoming a standard, non-invasive technique for pre
      surgical assessment of patients with medically intractable epilepsy. This study
      was designed to assess the BOLD response to focal IEDs recorded via simultaneous
      intracranial EEG-functional MRI (iEEG-fMRI). METHODS: Twelve consecutive patients
      undergoing intracranial video EEG monitoring were recruited for iEEG-fMRI studies
      at 3 T. Depth, subdural strip, or grid electrodes were implanted according to our
      standard clinical protocol. Subjects underwent 10-60 min of continuous iEEG-fMRI
      scanning. IEDs were marked, and the most statistically significant clusters of
      BOLD signal were identified (Z-score 2.3, p value < 0.05). We assessed the
      concordance between the locations of the BOLD response and the IED. Concordance
      was defined as a distance <1.0 cm between the IED and BOLD response location.
      Negative BOLD responses were not studied in this project. RESULTS: Nine patients
      (7 females) with a mean age of 31 years (range 22-56) had 11 different types of
      IEDs during fMR scanning. The IEDs were divided based on the location of the
      active electrode contact into mesial temporal, lateral temporal, and extra
      temporal. Seven (5 left) mesial temporal IED types were recorded in 5 patients
      (110-2092 IEDs per spike location). Six of these IEDs had concordant BOLD
      response in the ipsilateral mesial temporal structures, <1 cm from the most
      active contact. One of the two subjects with left lateral temporal IEDs had BOLD
      responses concordant with the location of the most active contact, as well other
      ipsilateral and contralateral sites. Notably, the remaining two subjects with
      extratemporal discharges showed no BOLD signal near the active electrode contact.
      CONCLUSIONS: iEEG-fMRI is a feasible and low-risk method for assessment of
      hemodynamic changes of very focal IEDs that may not be recorded by scalp EEG. A
      high concordance rate between the location of the BOLD response and IEDs was seen
      for mesial temporal (6/7) IEDs. Significant BOLD activation was also seen in
      areas distant from the active electrode and these sites exhibited maximal BOLD
      activation in the majority of cases. This implies that iEEG-fMRI may further
      describe the areas involved in the generation of IEDs beyond the vicinity of the
      electrode(s).

PMID- 25844326
TI  - Dyslexic children lack word selectivity gradients in occipito-temporal and
      inferior frontal cortex.
AB  - fMRI studies using a region-of-interest approach have revealed that the ventral
      portion of the left occipito-temporal cortex, which is specialized for
      orthographic processing of visually presented words (and includes the so-called
      "visual word form area", VWFA), is characterized by a posterior-to-anterior
      gradient of increasing selectivity for words in typically reading adults,
      adolescents, and children (e.g. Brem et al., 2006, 2009). Similarly, the left
      inferior frontal cortex (IFC) has been shown to exhibit a medial-to-lateral
      gradient of print selectivity in typically reading adults (Vinckier et al.,
      2007). Functional brain imaging studies of dyslexia have reported relative
      underactivity in left hemisphere occipito-temporal and inferior frontal regions
      using whole-brain analyses during word processing tasks. Hence, the question
      arises whether gradient sensitivities in these regions are altered in dyslexia.
      Indeed, a region-of-interest analysis revealed the gradient-specific functional
      specialization in the occipito-temporal cortex to be disrupted in dyslexic
      children (van der Mark et al., 2009). Building on these studies, we here (1)
      investigate if a word-selective gradient exists in the inferior frontal cortex in
      addition to the occipito-temporal cortex in normally reading children, (2)
      compare typically reading with dyslexic children, and (3) examine functional
      connections between these regions in both groups. We replicated the previously
      reported anterior-to-posterior gradient of increasing selectivity for words in
      the left occipito-temporal cortex in typically reading children, and its absence
      in the dyslexic children. Our novel finding is the detection of a pattern of
      increasing selectivity for words along the medial-to-lateral axis of the left
      inferior frontal cortex in typically reading children and evidence of functional
      connectivity between the most lateral aspect of this area and the anterior
      aspects of the occipito-temporal cortex. We report absence of an IFC gradient and
      connectivity between the lateral aspect of the IFC and the anterior occipito
      temporal cortex in the dyslexic children. Together, our results provide insights
      into the source of the anomalies reported in previous studies of dyslexia and add
      to the growing evidence of an orthographic role of IFC in reading. 

PMID- 25844328
TI  - Schizophrenia risk variants modulate white matter volume across the psychosis
      spectrum: evidence from two independent cohorts.
AB  - Polygenic risk scores, based on risk variants identified in genome-wide
      association-studies (GWAS), explain a considerable portion of the heritability
      for schizophrenia (SZ) and bipolar disorder (BD). However, little is known about
      the combined effects of these variants, although polygenic neuroimaging has
      developed into a powerful tool of translational neuroscience. In this study, we
      used genome wide significant SZ risk variants to test the predictive capacity of
      the polygenic model and explored potential associations with white matter volume,
      a key candidate in imaging phenotype for psychotic disorders. By calculating the
      combined additive schizophrenia risk of seven SNPs (significant hits from a
      recent schizophrenia GWAS study), we show that increased additive genetic risk
      for SZ was associated with reduced white matter volume in a group of participants
      (n = 94) consisting of healthy individuals, SZ first-degree relatives, SZ
      patients and BD patients. This effect was also seen in a second independent
      sample of healthy individuals (n = 89). We suggest that a moderate portion of
      variance (~4%) of white matter volume can be explained by the seven hits from the
      recent schizophrenia GWAS. These results provide evidence for associations
      between cumulative genetic risk for schizophrenia and intermediate neuroimaging
      phenotypes in models of psychosis. Our work contributes to a growing body of
      literature suggesting that polygenic risk may help to explain white matter
      alterations associated with familial risk for psychosis. 

PMID- 25844329
TI  - Comparing a diffusion tensor and non-tensor approach to white matter fiber
      tractography in chronic stroke.
AB  - Diffusion tensor imaging (DTI)-based tractography has been used to demonstrate
      functionally relevant differences in white matter pathway status after stroke.
      However, it is now known that the tensor model is insensitive to the complex
      fiber architectures found in the vast majority of voxels in the human brain. The
      inability to resolve intra-voxel fiber orientations may have important
      implications for the utility of standard DTI-based tract reconstruction methods.
      Intra-voxel fiber orientations can now be identified using novel, tensor-free
      approaches. Constrained spherical deconvolution (CSD) is one approach to
      characterize intra-voxel diffusion behavior. In the current study, we performed
      DTI- and CSD-based tract reconstruction of the corticospinal tract (CST) and
      corpus callosum (CC) to test the hypothesis that characterization of complex
      fiber orientations may improve the robustness of fiber tract reconstruction and
      increase the sensitivity to identify functionally relevant white matter
      abnormalities in individuals with chronic stroke. Diffusion weighted magnetic
      resonance imaging was performed in 27 chronic post-stroke participants and 12
      healthy controls. Transcallosal pathways and the CST bilaterally were
      reconstructed using DTI- and CSD-based tractography. Mean fractional anisotropy
      (FA), apparent diffusion coefficient (ADC), axial diffusivity (AD), and radial
      diffusivity (RD) were calculated across the tracts of interest. The total number
      and volume of reconstructed tracts was also determined. Diffusion measures were
      compared between groups (Stroke, Control) and methods (CSD, DTI). The
      relationship between post-stroke motor behavior and diffusion measures was
      evaluated. Overall, CSD methods identified more tracts than the DTI-based
      approach for both CC and CST pathways. Mean FA, ADC, and RD differed between DTI
      and CSD for CC-mediated tracts. In these tracts, we discovered a difference in FA
      for the CC between stroke and healthy control groups using CSD but not DTI. CSD
      identified ipsilesional CST pathways in 9 stroke participants who did not have
      tracts identified with DTI. Additionally, CSD differentiated between stroke
      ipsilesional and healthy control non-dominant CST for several measures (number of
      tracts, tract volume, FA, ADC, and RD) whereas DTI only detected group
      differences for number of tracts. In the stroke group, motor behavior correlated
      with fewer diffusion metrics derived from the DTI as compared to CSD
      reconstructed ipsilesional CST and CC. CSD is superior to DTI-based tractography
      in detecting differences in diffusion characteristics between the nondominant
      healthy control and ipsilesional CST. CSD measures of microstructure tissue
      properties related to more motor outcomes than DTI measures did. Our results
      suggest the potential utility and functional relevance of characterizing complex
      fiber organization using tensor-free diffusion modeling approaches to investigate
      white matter pathways in the brain after stroke. 

PMID- 25844330
TI  - Exposing asymmetric gray matter vulnerability in amyotrophic lateral sclerosis.
AB  - Limb weakness in amyotrophic lateral sclerosis (ALS) is typically asymmetric.
      Previous studies have identified an effect of limb dominance on onset and spread
      of weakness, however relative atrophy of dominant and non-dominant brain regions
      has not been investigated. Our objective was to use voxel-based morphometry (VBM)
      to explore gray matter (GM) asymmetry in ALS, in the context of limb dominance.
      30 ALS subjects were matched with 17 healthy controls. All subjects were right
      handed. Each underwent a structural MRI sequence, from which GM segmentations
      were generated. Patterns of GM atrophy were assessed in ALS subjects with first
      weakness in a right-sided limb (n = 15) or left-sided limb (n = 15). Within each
      group, a voxelwise comparison was also performed between native and mirror GM
      images, to identify regions of hemispheric GM asymmetry. Subjects with ALS showed
      disproportionate atrophy of the dominant (left) motor cortex hand area,
      irrespective of the side of first limb weakness (p < 0.01). Asymmetric atrophy of
      the left somatosensory cortex and temporal gyri was only observed in ALS subjects
      with right-sided onset of limb weakness. Our VBM protocol, contrasting native and
      mirror images, was able to more sensitively detect asymmetric GM pathology in a
      small cohort, compared with standard methods. These findings indicate particular
      vulnerability of dominant upper limb representation in ALS, supporting previous
      clinical studies, and with implications for cortical organisation and selective
      vulnerability. 

PMID- 25844331
TI  - T2 mapping outperforms normalised FLAIR in identifying hippocampal sclerosis.
AB  - RATIONALE: Qualitatively, FLAIR MR imaging is sensitive to the detection of
      hippocampal sclerosis (HS). Quantitative analysis of T2 maps provides a useful
      objective measure and increased sensitivity over visual inspection of T2-weighted
      scans. We aimed to determine whether quantification of normalised FLAIR is as
      sensitive as T2 mapping in detection of HS. METHOD: Dual echo T2 and FLAIR MR
      images were retrospectively analysed in 27 patients with histologically confirmed
      HS and increased T2 signal in ipsilateral hippocampus and 14 healthy controls.
      Regions of interest were manually segmented in all hippocampi aiming to avoid
      inclusion of CSF. Hippocampal T2 values and measures of normalised FLAIR Signal
      Intensity (nFSI) were compared in healthy and sclerotic hippocampi. RESULTS: HS
      was identified on T2 values with 100% sensitivity and 100% specificity. HS was
      identified on nFSI measures with 60% sensitivity and 93% specificity. CONCLUSION:
      T2 mapping is superior to nFSI for identification of HS.

PMID- 25844332
TI  - Is the double channel gastroscope useful in endoscopic mucosal resection for
      large sessile colon polyps?

PMID- 25844333
TI  - Which needle is better for diagnosing subepithelial lesions?

PMID- 25844334
TI  - Is endoscopic ultrasonography-guided fine needle aspiration trailblazing in
      tissue sampling of adrenal masses?

PMID- 25844335
TI  - Endoscopic management of nonvariceal upper gastrointestinal bleeding: state of
      the art.
AB  - Nonvariceal upper gastrointestinal (GI) bleeding is one of the most common
      reasons for hospitalization and a major cause of morbidity and mortality
      worldwide. Recently developed endoscopic devices and supporting apparatuses can
      achieve endoscopic hemostasis with greater safety and efficiency. With these
      advancements in technology and technique, gastroenterologists should have no
      concerns regarding the management of acute upper GI bleeding, provided that they
      are well prepared and trained. However, when endoscopic hemostasis fails,
      endoscopy should not be continued. Rather, endoscopists should refer patients to
      radiologists and surgeons without any delay for evaluation regarding the
      appropriateness of emergency interventional radiology or surgery. 

PMID- 25844336
TI  - Endoscopic management of mallory-weiss tearing.
AB  - Mallory-Weiss tearing (MWT) is a common cause of non-variceal upper
      gastrointestinal bleeding. Although the majority of patients with bleeding MWT
      require no intervention other than hemodynamic supports, spectrum of MWT is wide,
      and the condition sometimes results in a fatal outcome. Endoscopic management to
      stop the bleeding may be required during the index endoscopy, especially in those
      with active bleeding or stigmata of recurrent bleeding. Most commonly used
      endoscopic treatment for actively bleeding MWT is injection therapy, argon plasma
      coagulation, hemoclip placement, and band ligation. Selection of the optimal
      endoscopic hemostasis depends on the physician's ability and patient's clinical
      status. 

PMID- 25844337
TI  - Endoscopic management of peptic ulcer bleeding.
AB  - Acute upper gastrointestinal bleeding is a common medical emergency around the
      world and the major cause is peptic ulcer bleeding. Endoscopic treatment is
      fundamental for the management of peptic ulcer bleeding. Despite recent advances
      in endoscopic treatment, mortality from peptic ulcer bleeding has still remained
      high. This is because the disease often occurs in elderly patients with frequent
      comorbidities and are taking ulcerogenic medications. Therefore, the management
      of peptic ulcer bleeding is still a challenge for clinicians. This article
      reviews the various endoscopic methods available for management of peptic ulcer
      bleeding and the techniques in using these methods. 

PMID- 25844338
TI  - Endoscopic Management of Dieulafoy's Lesion.
AB  - A Dieulafoy's lesion is a vascular abnormality consisting of a large caliber
      persistent tortuous submucosal artery. A small mucosal defect with the eruption
      of this protruding vessel can cause bleeding. In fact, a Dieulafoy's lesion is a
      relatively rare but potentially life-threatening condition. It accounts for 1% to
      2% of cases of acute gastrointestinal bleeding. Although there is no consensus on
      the treatment of Dieulafoy's lesions; treatment options depend on the mode of
      presentation, site of the lesion, and available expertise. Endoscopic therapy is
      usually successful in achieving primary hemostasis, with hemostasis success rates
      reaching 75% to 100%. Although various therapeutic endoscopic methods are used to
      control bleeding in Dieulafoy's lesions, the best method for endoscopic
      intervention is not clear. Combination endoscopic therapy is known to be superior
      to monotherapy because of a lower rate of recurrent bleeding. In addition,
      mechanical therapies including hemostatic clipping and endoscopic band ligation
      are more effective and successful in controlling bleeding than other endoscopic
      methods. Advances in endoscopic techniques have reduced mortality in patients
      with Dieulafoy's lesion-from 80% to 8%-and consequently, the need for surgical
      intervention has been reduced. Currently, surgical intervention is used for cases
      that fail therapeutic endoscopic or angiographic interventions. 

PMID- 25844339
TI  - Endoscopic management of tumor bleeding from inoperable gastric cancer.
AB  - Tumor bleeding is not a rare complication in patients with inoperable gastric
      cancer. Endoscopy has important roles in the diagnosis and primary treatment of
      tumor bleeding, similar to its roles in other non-variceal upper gastrointestinal
      bleeding cases. Although limited studies have been performed, endoscopic therapy
      has been highly successful in achieving initial hemostasis. One or a combination
      of endoscopic therapy modalities, such as injection therapy, mechanical therapy,
      or ablative therapy, can be used for hemostasis in patients with endoscopic
      stigmata of recent hemorrhage. However, rebleeding after successful hemostasis
      with endoscopic therapy frequently occurs. Endoscopic therapy may be a treatment
      option for successfully controlling this rebleeding. Transarterial embolization
      or palliative surgery should be considered when endoscopic therapy fails. For
      primary and secondary prevention of tumor bleeding, proton pump inhibitors can be
      prescribed, although their effectiveness to prevent bleeding remains to be
      investigated. 

PMID- 25844340
TI  - Guidelines for video capsule endoscopy: emphasis on Crohn's disease.
AB  - Video capsule endoscopy (VCE) is an ingestible video camera that transmits high
      quality images of the small intestinal mucosa. This makes the small intestine
      more readily accessible to physicians investigating the presence of small bowel
      disorders, such as Crohn's disease (CD). Although VCE is frequently performed in
      Korea, there are no evidence-based guidelines on the appropriate use of VCE in
      the diagnosis of CD. To provide accurate information and suggest correct testing
      approaches for small bowel diseases, the Korean Gut Image Study Group, part of
      the Korean Society of Gastrointestinal Endoscopy, developed guidelines on VCE.
      Teams were set up to develop guidelines on VCE. Four areas were selected:
      diagnosis of obscure gastrointestinal bleeding, small bowel preparation for VCE,
      diagnosis of CD, and diagnosis of small bowel tumors. Three key questions were
      selected regarding the role of VCE in CD. In preparing these guidelines, a
      systematic literature search, evaluation, selection, and meta-analysis were
      performed. After writing a draft of the guidelines, the opinions of various
      experts were solicited before producing the final document. These guidelines are
      expected to play a role in the diagnosis of CD. They will need to be updated as
      new data and evidence become available. 

PMID- 25844341
TI  - Use of a double-channel gastroscope reduces procedural time in large left-sided
      colonic endoscopic mucosal resections.
AB  - BACKGROUND/AIMS: Endoscopic mucosal resection (EMR) of large colorectal lesions
      is associated with increased procedural time. The objective of this study was to
      evaluate the effect of double-channel gastroscope (DCG) use on the procedural
      time of EMRs in the rectosigmoid area. METHODS: All EMRs for sessile or flat
      rectosigmoid lesions >=2 cm performed between July 2011 and September 2012 were
      retrospectively analyzed. RESULTS: There were 55 lesions >=2 cm in the
      rectosigmoid area in 55 patients, of which 26 were removed by EMR using a DCG (DC
      group) and 29 by using an ordinary colonoscope or gastroscope (OS group). The
      mean size of the removed polyps, morphology, adverse effects, and other
      parameters were similar between the two groups. The mean procedural time was
      significantly lower in the DC group than in the OS group (24.4+/-18.3 minutes vs.
      36.3+/-24.4 minutes, p=0.015). Moreover, in a subgroup of patients with polyps
      >40 mm, the statistical difference in the mean procedural time between the DC and
      OS groups was even more pronounced (33+/-21 minutes vs. 58.7+/-20.6 minutes,
      p=0.004). CONCLUSIONS: Our data suggest that the use of a DCG in the resection of
      large nonpedunculated rectosigmoid lesions significantly reduces the procedural
      time.

PMID- 25844342
TI  - Light-emitting diode-assisted narrow band imaging video endoscopy system in head
      and neck cancer.
AB  - BACKGROUND/AIMS: To validate the effectiveness of a newly developed light
      emitting diode (LED)-narrow band imaging (NBI) system for detecting early
      malignant tumors in the oral cavity. METHODS: Six men (mean age, 51.5 years) with
      early oral mucosa lesions were screened using both the conventional white light
      and LED-NBI systems. RESULTS: Small elevated or ulcerative lesions were found
      under the white light view, and typical scattered brown spots were identified
      after shifting to the LED-NBI view for all six patients. Histopathological
      examination confirmed squamous cell carcinoma. The clinical stage was early
      malignant lesions (T1), and the patients underwent wide excision for primary
      cancer. This is the pilot study documenting the utility of a new LED-NBI system
      as an adjunctive technique to detect early oral cancer using the diagnostic
      criterion of the presence of typical scattered brown spots in six high-risk
      patients. CONCLUSIONS: Although large-scale screening programs should be
      established to further verify the accuracy of this technology, its lower power
      consumption, lower heat emission, and higher luminous efficiency appear promising
      for future clinical applications.

PMID- 25844343
TI  - Clinical outcomes of argon plasma coagulation therapy for early gastric
      neoplasms.
AB  - BACKGROUND/AIMS: Argon plasma coagulation (APC) has some merits in the treatment
      of gastric neoplasms including a shorter operative time and fewer complications
      compared with endoscopic mucosal resection or endoscopic submucosal dissection.
      However, there are few reports on the outcomes of gastric neoplasms treated using
      APC. The aim of this study was to evaluate APC in the treatment of early gastric
      neoplasms in terms of clinical efficacy, safety, and local recurrence. METHODS:
      We enrolled 28 patients who received APC therapy at the Kyungpook National
      University Hospital between May 2007 and April 2013. Clinical outcomes were
      analyzed. RESULTS: The median follow-up period was 24.8 months (range, 2 to 78).
      Among the 28 lesions treated using the APC procedure, tumor recurrence was
      encountered in seven lesions (25.0%). Recurrence was found in 50% (5/10) of
      single APC cases and 11% (2/18) of rescue APC cases. The mean time to recurrence
      was 16.1 months (range, 2 to 78). There were no serious APC-related complications
      such as perforation, bleeding, or infection. CONCLUSIONS: APC therapy can be a
      useful treatment with a favorable safety profile for patients with early gastric
      neoplasms. However, further studies are necessary to determine the long-term
      prognosis of patients undergoing this treatment.

PMID- 25844344
TI  - Yields and Utility of Endoscopic Ultrasonography-Guided 19-Gauge Trucut Biopsy
      versus 22-Gauge Fine Needle Aspiration for Diagnosing Gastric Subepithelial
      Tumors.
AB  - BACKGROUND/AIMS: To evaluate the yields and utility of 19-gauge (G) Trucut biopsy
      (TCB) versus 22 G fine needle aspiration (FNA) for diagnosing gastric
      subepithelial tumors (SETs). METHODS: We retrieved data for 152 patients with a
      gastric SET larger than 2 cm who had undergone endoscopic ultrasonography (EUS)
      guided 19 G TCB (n=90) or 22 G FNA (n=62). Relevant clinical, tumor-specific, and
      EUS procedural information was reviewed retrospectively. RESULTS: A specific
      diagnosis was made for 76 gastrointestinal stromal tumors (GISTs) and 51 non-GIST
      SETs. The diagnostic yield of TCB was greater than that of FNA (77.8% vs. 38.7%,
      p<0.001). The percentage of non-diagnostic specimens (suspicious and
      insufficient) was significantly lower in the TCB group (6.7% and 15.5%,
      respectively) than in the FNA group (22.6% and 38.7%, respectively; both
      p<0.001). TCB accurately diagnosed 90.9% of GISTs and 81.1% of non-GIST SETs,
      whereas FNA accurately diagnosed 68.8% of GISTs and 14.3% of non-GIST SETs. There
      were nine technical failures with TCB, and the rate of adverse events did not
      differ between the groups (TCB vs. FNA, 3.3% vs. 8.1%; p=0.27). CONCLUSIONS:
      Nineteen-gauge TCB is safe and highly valuable for diagnosing gastric SETs larger
      than 2 cm if technical failure can be avoided.

PMID- 25844345
TI  - Endoscopic ultrasonography-guided ethanol ablation for small pancreatic
      neuroendocrine tumors: results of a pilot study.
AB  - BACKGROUND/AIMS: Endoscopic ultrasonography (EUS)-guided ethanol ablation is
      gaining popularity for the treatment of focal pancreatic lesions. The aim of this
      study was to evaluate the safety, feasibility, and treatment response after EUS
      guided ethanol injection for small pancreatic neuroendocrine tumors (p-NETs).
      METHODS: This was a retrospective analysis of a prospectively collected database
      including 11 consecutive patients with p-NETs who underwent EUS-guided ethanol
      injection. RESULTS: EUS-guided ethanol injection was successfully performed in 11
      patients with 14 tumors. The final diagnosis was based on histology and clinical
      signs as follows: 10 non-functioning neuroendocrine tumors and four insulinomas.
      During follow-up (median, 370 days; range, 152 to 730 days), 10 patients
      underwent clinical follow-up after treatment, and one patient was excluded
      because of loss to follow-up. A single treatment session with an injection of 0.5
      to 3.8 mL of ethanol resulted in complete responses (CRs) at the 3-month
      radiologic imaging for seven of 13 tumors (response rate, 53.8%). Multiple
      treatment sessions performed in three tumors with residual viable enhancing
      tissue increased the number of tumors with CRs to eight of 13 (response rate,
      61.5%). Mild pancreatitis occurred in three of 11 patients. CONCLUSIONS: EUS
      guided ethanol injection appears to be a safe, feasible, and potentially
      effective method for treating small p-NETs in patients who are poor surgical
      candidates.

PMID- 25844346
TI  - Endoscopic ultrasound-guided fine-needle aspiration of the adrenal glands:
      analysis of 21 patients.
AB  - BACKGROUND/AIMS: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA)
      cytology of adrenal masses helps in etiological diagnosis. The aim of this study
      was to evaluate the diagnostic yield of EUS-FNA of adrenal masses in cases where
      other imaging methods failed and/or were not feasible. METHODS: Twenty-one
      consecutive patients with adrenal masses, in whom adrenal FNA was performed
      because conventional imaging modalities failed and/or were not feasible, were
      prospectively evaluated over a period of 3 years. RESULTS: Of the 21 patients
      (mean age, 56+/-12.2 years; male:female ratio, 2:1), 12 had pyrexia of unknown
      origin and the other nine underwent evaluation for metastasis. The median lesion
      size was 2.4*1.6 cm. Ten patients were diagnosed with tuberculosis (shown by the
      presence of caseating granulomas [n=10] and acid-fast bacilli [n=4]). Two
      patients had EUS-FNA results suggestive of histoplasmosis. The other patients had
      metastatic lung carcinoma (n=6), hepatocellular carcinoma (n=1), and adrenal
      lipoma (n=1) and adrenal myelolipoma (n=1). EUS results were not suggestive of
      any particular etiology. No procedure-related adverse events occurred.
      CONCLUSIONS: EUS-FNA is a safe and effective method for evaluating adrenal
      masses, and it yields diagnosis in cases where tissue diagnosis is impossible or
      has failed using conventional imaging modalities.

PMID- 25844347
TI  - Peripheral facial nerve palsy after therapeutic endoscopy.
AB  - Peripheral facial nerve palsy (FNP) is a mononeuropathy that affects the
      peripheral part of the facial nerve. Primary causes of peripheral FNP remain
      largely unknown, but detectable causes include systemic infections (viral and
      others), trauma, ischemia, tumor, and extrinsic compression. Peripheral FNP in
      relation to extrinsic compression has rarely been described in case reports.
      Here, we report a case of a 71-year-old man who was diagnosed with peripheral FNP
      following endoscopic submucosal dissection. This case is the first report of the
      development of peripheral FNP in a patient undergoing therapeutic endoscopy. We
      emphasize the fact that physicians should be attentive to the development of
      peripheral FNP following therapeutic endoscopy. 

PMID- 25844348
TI  - Eosinophilic gastroenteritis due to rhus ingestion presenting with
      gastrointestinal hemorrhage.
AB  - Rhus-related illnesses in Korea are mostly caused by ingestion of parts of the
      Rhus tree. Contact dermatitis occurrence after ingestion of Rhus-related food is
      very common in Korea. However, Rhus-related gastrointestinal disease is very
      rare. Herein, we present a case of eosinophilic gastroenteritis caused by Rhus
      ingestion. A 75-year-old woman was admitted with hematemesis and hematochezia
      after Rhus extract ingestion. Routine laboratory tests revealed leukocytosis
      without eosinophilia. Endoscopy showed friable and granular mucosal changes with
      touch bleeding in the second portion of the duodenum. Abdominal computed
      tomography revealed edematous wall thickening of the duodenum and proximal
      jejunal loops. Patch testing with Rhus extracts showed a strong positive
      reaction, suggesting Rhus as the allergen. Her symptoms improved after avoidance
      of the allergen. 

PMID- 25844349
TI  - "Cat scratch colon" in a patient with ischemic colitis.
AB  - "Cat scratch colon" is a gross finding characterized by hemorrhagic mucosal
      scratches on colonoscopy. It is usually associated with a normal colon and is
      rarely associated with collagenous colitis. In a previous report, cat scratch
      colon was noted in the cecum and ascending colon, but has also been observed in
      the distal transverse colon. The patient in this study was also diagnosed with
      ischemic colitis that may have played a role in the development of cat scratch
      colon. 

PMID- 25844350
TI  - Imaging Vascular Disease and Amyloid in the Aging Brain: Implications for
      Treatment.
AB  - Vascular risk factors (e.g. hypertension, dyslipidemia and diabetes) are well
      known risk factors for Alzheimer' disease. These vascular risk factors lead to
      vascular brain injuries, which also increase the likelihood of dementia. The
      advent of amyloid PET imaging has helped establish that vascular risk factors
      also lead to Alzheimer's disease via pathways that are independent from vascular
      brain injuries, at least, when vascular brain injuries are measured as white
      matter lesions and infarcts. While vascular brain injuries (white matter lesions
      and infarcts) do not seem to influence amyloid pathology, some evidence from
      amyloid imaging suggests that increased vascular risk is related to increased
      amyloid burden. Furthermore, while vascular brain injuries and amyloid have an
      additive and independent impact on brain integrity, vascular risk factors might
      potentiate the impact of amyloid on cortical thickness on brain regions
      vulnerable to Alzheimer's disease. New research should further explore and
      confirm, or refute, possible interactions between amyloid and vascular risk
      factors on brain integrity and cognition. Neuroimaging tools used to assess
      vascular brain integrity should also be expanded. Measuring cortical blood flow
      or damage to the capillary system might, for instance, give insight about how
      vascular risk factors can be associated to amyloid burden and impact. These
      findings also stress the need for monitoring vascular risk factors in midlife as
      a strategy for Alzheimer's disease prevention.

PMID- 25844351
TI  - Feasibility of implementing a surgical student internship program in South Korea.
AB  - PURPOSE: Despite recommendations for introducing student internships (SI) in
      undergraduate medical education in Korea, the feasibility of surgical SIs has not
      been demonstrated in the Korean context. We thus identified tasks that could be
      performed by surgical student interns in a Korean education hospital. METHODS:
      The opinions of surgery clerkship directors of medical schools nationwide,
      regarding the tasks, symptoms and signs, disease entities, and procedures that
      student interns could perform in their hospitals, were subjected to descriptive
      analysis. RESULTS: Out of the 41 medical schools in Korea, 32 responded. Five
      implemented an optimal-quality SI program. Two schools considered third-year
      clerkship as SI. The respondents replied that student interns could be involved
      in basic nonspecific tasks such as history taking, physical examination, medial
      recording, reporting patients' status, and assisting during surgery. However,
      more surgery-specific tasks such as perioperative management or caring for a
      patient with acute abdominal pain were considered difficult for student interns
      to encounter in the Korean context. CONCLUSION: Surgical educators should
      determine a specific role for student interns and encourage them to perform
      surgery-specific tasks. We recommend societal and system support, and curriculum
      renovation to establish an SI program in Korea.

PMID- 25844352
TI  - The neutrophil to lymphocyte ratio can discriminate anaplastic thyroid cancer
      against poorly or well differentiated cancer.
AB  - PURPOSE: We evaluated the capability of the neutrophil to lymphocyte ratio (NLR)
      as a diagnostic tool to discriminate between poorly differentiated thyroid cancer
      (PDTC) and anaplastic thyroid cancer (ATC) from well differentiated thyroid
      cancer (WDTC). METHODS: The NLR of 3,870 patients with benign and malignant
      thyroid tumors were analyzed. There were 436 benign, 3,364 papillary, 15
      medullary, 34 follicular or hurthle type, 14 PDTC, and 7 ATC type neoplasms.
      Patients were divided into two groups: a high NLR group and a low NLR group.
      RESULTS: The NLR of all 3,870 patients was a normal distribution, and the median
      value was 1.57. Advanced stage cancer, such as T3 or T4 was high (30.4% vs.
      26.5%, P = 0.027), and cancer-specific deaths were also high (1.2% vs. 0.4%, P =
      0.018) in the high NLR group. The proportion of PDTC (0.6% vs. 0.1%) and ATC
      (0.3% vs. 0.1%) was higher in the high NLR group. The NLR can discriminate
      between PTC, PDTC, and ATC (P = 0.035, P = 0.002, and P = 0.025, respectively),
      and the cutoff value was 3.8 between PDTC versus ATC. None of the NLR of PDTC
      exceeded the cutoff value of 3.8. CONCLUSION: NLR can play a relevant role as a
      discriminating tool and may be considered as a new diagnostic criterion in
      discriminating as well as in selecting therapeutic approaches to these aggressive
      forms of thyroid cancer.

PMID- 25844353
TI  - The benefits of preincision ropivacaine infiltration for reducing postoperative
      pain after robotic bilateral axillo-breast approach thyroidectomy: a prospective,
      randomized, double-blind, placebo-controlled study.
AB  - PURPOSE: The aim of this study was to evaluate the effects of preoperative
      ropivacaine infiltration in patients undergoing robotic thyroidectomy using the
      bilateral axillary breast approach method. METHODS: Using a randomized, double
      blind study design, 34 consecutive female patients who underwent robotic
      thyroidectomy were randomly assigned to receive local infiltration to the skin
      flap site using either only 0.9% saline solution, 3 mL/kg (group C, n = 17) or
      0.1% ropivacaine with saline, 3 mg/kg (group L, n = 17). Local anesthetic was
      administered prior to skin incision after the induction of general anesthesia.
      Postoperative pain was rated at 2, 6, 18, 30, 42, and 66 hours postoperatively by
      visual analogue scale (VAS) score. The bottom hit counts (BHC) from patient
      controlled analgesia and fentanyl consumption were evaluated. CRP levels, mean
      blood pressure (BP), and heart rate (HR) were also evaluated. RESULTS: VAS pain
      scores were significantly lower in group L than in group C from 2 to 42 hours (P
      < 0.05). Fentanyl use for analgesia and BHC were also significantly lower in
      group L compared with group C during the first postoperative 6 and 2 hours,
      respectively (P < 0.05). The total consumption of fentanyl was significantly
      lower in group L than in group C (P = 0.009). No significant differences were
      noted for baseline, postoperative mean BP, or HR. CONCLUSION: Preoperative
      infiltration using ropivacaine with saline to all flap sites is a safe and
      effective method for reducing postoperative pain and postoperative fentanyl
      consumption in patients with robotic thyroidectomy.

PMID- 25844354
TI  - Ki-67 and p53 expression as a predictive marker for early postoperative
      recurrence in pancreatic head cancer.
AB  - PURPOSE: This study aimed to evaluate the clinical significance of Ki-67 and p53
      expressions in patients with pancreatic head cancer. METHODS: Between May 2008
      and April 2013, immunohistochemical staining for Ki-67 and p53 was performed in
      34 patients with pancreatic head cancer (ductal adenocarcinoma). All 34 patients
      underwent pancreaticoduodenectomy at Chonnam National University Hwasun Hospital,
      Hwasun, Korea. Clinical and histopathological characteristics were analyzed,
      relative to p53 expression. RESULTS: Thirty (88.2%) and twenty-one (61.7%) of the
      34 pancreatic head cancers exhibited positive expression of Ki-67 and p53,
      respectively. Patients expressing Ki-67 and p53 experienced more frequent tumor
      recurrences within 1 year after surgical resection (P = 0.003 and P = 0.030,
      respectively). However, no correlation was detected between Ki-67 and p53
      expression. Ki-67 expression was correlated with pathological grade, lymph node
      metasatsis, and clinical stage (P < 0.05). Importantly, Ki-67 was the independent
      predictive factor for postoperative recurrence within 1 year in both univariable
      and multivariable analyses (odds ratio, 27.219; 95% confidence interval, 1.403
      528.135; P = 0.029). CONCLUSION: The expression of Ki-67 and p53 are
      significantly related to early postoperative recurrence within 1 year after
      surgical resection in pancreatic head cancer. Especially, Ki-67 was the
      independent predictive factor for postoperative recurrence within 1 year.
      Therefore, immunohistochemical staining for Ki-67 and p53 may be applied as a
      predictive marker for early postoperative recurrence in pancreatic head cancer.

PMID- 25844355
TI  - Follow-up results of acute portal and splenic vein thrombosis with or without
      anticoagulation therapy after hepatobiliary and pancreatic surgery.
AB  - PURPOSE: Acute portal and splenic vein thrombosis (APSVT) after hepatobiliary and
      pancreatic (HBP) surgery is a rare but serious complication and a treatment
      strategy has not been well established. To assess the safety and efficacy of
      anticoagulation therapy for treating APSVT after HBP surgery. METHODS: We
      performed a retrospective case-control study of 82 patients who were diagnosed
      with APSVT within 4 weeks after HBP surgery from October 2002 to November 2012 at
      a single institute. We assigned patients to the anticoagulation group (n = 32) or
      nonanticoagulation group (n = 50) and compared patient characteristics,
      complications, and the recanalization rate of APSVT between these two groups.
      RESULTS: APSVT was diagnosed a mean of 8.6 +/- 4.8 days after HBP surgery.
      Patients' characteristics were not significantly different between the two
      groups. There were no bleeding complications related to anticoagulation therapy.
      The 1-year cumulative recanalization rate of anticoagulation group and
      nonanticoagulation group were 71.4% and 34.1%, respectively, which is
      statistically significant (log-rank test, P = 0.0001). In Cox regression model
      for multivariate analysis, independent factors associated with the recanalization
      rate of APSVT after HBP surgery were anticoagulation therapy (P = 0.003; hazard
      ration [HR], 2.364; 95% confidence interval [CI], 1.341-4.168), the absence of a
      vein reconstruction procedure (P = 0.027; HR, 2.557; 95% CI, 1.111-5.885), and
      operation type (liver resection rather than pancreatic resection; P = 0.005, HR,
      2.350; 95% CI, 1.286-4.296). CONCLUSION: Anticoagulation therapy appears to be a
      safe and effective treatment for patients with APSVT after HBP surgery. Further
      prospective studies of larger patient populations are necessary to confirm our
      findings.

PMID- 25844356
TI  - The effect of long Roux-en-Y gastrojejunostomy in gastric cancer patients with
      type 2 diabetes and body mass index < 35 kg/m(2): preliminary results.
AB  - PURPOSE: We applied a long Roux-en-Y (RY) gastrojejunostomy (bypassed jejunum
      over 100 cm) as a reconstruction method for diabetes control to gastric cancer
      patients with type 2 diabetes and body mass index (BMI) < 35 kg/m(2). The effect
      of this procedure on diabetes control was assessed. METHODS: We prospectively
      performed modified RY gastrojejunostmy after curative radical distal gastrectomy.
      Thirty patients had completed a 1-year follow-up. Patients were followed
      concerning their diabetic status. The factors included in the investigation were
      length of bypassed jejunum, BMI and its reduction ratio, glycated hemoglobin
      (HbA1c), fasting blood glucose, and duration of diabetes. Diabetic status after
      surgery was assessed in three categories: remission, improvement, and stationary.
      In evaluation of surgical effects on diabetes control, remission and improvement
      groups were regarded as effective groups, while stationary was regarded as an
      ineffective group. RESULTS: At postoperative one year, statistical significance
      was observed in the mean BMI and HbA1c. Diabetes control was achieved in 50% of
      the patients (remission, 30%; improvement, 20%). BMI reduction ratio,
      preoperative HbA1c, and duration of diabetes were correlated to the status of
      type 2 diabetes mellitus. The preoperative HbA1c was the most influential
      predictor in diabetic control. CONCLUSION: The effect of long RY
      gastrojejunostomy after gastrectomy for diabetes control could be contentious but
      an applicable reconstruction method for diabetes control in gastric cancer
      patients with type 2 diabetes and BMI < 35 kg/m(2). Diabetes remission is
      expected to be higher in patients with greater BMI reduction, short duration of
      diabetes, and lower preoperative HbA1c.

PMID- 25844357
TI  - De novo malignancy after liver transplantation: a single-center experience of 14
      cases.
AB  - PURPOSE: The aim of this study is to evaluate the incidence of de novo malignancy
      after liver transplantation (LT) and compare with those among the general Chinese
      population. METHODS: A total of 466 patients who had a minimum follow-up time of
      6 months were enrolled in the study. All data of medical records and follow up
      were retrospectively reviewed. RESULTS: The incidence rate of de novo malignancy
      was 3.0% (14 in 466 patients). The median elapsed time from transplant to the
      diagnosis of de novo malignancy was 42 months (range, 6 to 106 months). The
      cumulative risk for development of de novo malignancy was 1.6%, 2.7%, and 8.2% at
      3, 5 and 10 years after LT, respectively. The patients were all male. The types
      of de novo tumors included digestive system tumor (8 in 14), lung cancer (2 in
      14), urologic neoplasm (2 in 14), and hematologic malignant tumor (2 in 14). Over
      a mean follow-up of 24 months after diagnosis of de novo malignancy, 7 patients
      (50.0%) died; the overall 5-year patient survival rate was 54.5%. The relative
      risk of malignancy following LT was 9.5 folds higher than the general Chinese
      population. CONCLUSION: The relative risk of malignancy following LT was much
      higher than the general Chinese population. Digestive system tumor is the most
      common type of de novo malignancy after LT in China.

PMID- 25844358
TI  - Double common bile duct with an ectopic drainage into the stomach.
AB  - Double common bile duct (DCBD) is a rare congenital anomaly among biliary
      anomalies. The anomaly has an important clinical implication because of its
      association with anomalous pancreaticobiliary ductal union (APBDU) and upper
      gastrointestinal cancers. In addition, if one of the two common bile ducts is
      mistaken for the cystic duct during surgery, bile duct injury is likely to occur.
      Treatment depends on the coexistence of concomitant cancer and APBDU. A 54-year
      old male diagnosed of gastric cancer was referred for surgery. During surgery, we
      incidentally detected bile leak from the tubular structure around the
      hepatoduodenal ligament. We performed intraoperative cholangiogram by cannulizing
      into the tubular structure, and confirmed the tubular duct as the accessory bile
      duct with an ectopic drainage into the stomach, which was connected to the
      proximal common bile duct. In this study, we report a rare case of DCBD with an
      ectopic drainage into the stomach and review the literature. 

PMID- 25844359
TI  - Experience of direct percutaneous sac injection in type II endoleak using cone
      beam computed tomography.
AB  - Cone beam CT, usually used in dental area, could easily obtain 3-dimensional
      images using cone beam shaped ionized radiation. Cone beam CT is very useful for
      direct percutaneous sac injection (DPSI) which needs very precise measurement to
      avoid puncture of inferior vena cava or vessel around sac or stent graft. Here we
      describe two cases of DPSI using cone beam CT. In case 1, a 79-year-old male had
      widening of preexisted type II endoleak after endovascular aneurysm repair
      (EVAR). However, transarterial embolization failed due to tortuous collateral
      branches of lumbar arteries. In case 2, a 72-year-old female had symptomatic sac
      enlargement by type II endoleak after EVAR. However, there was no route to
      approach the lumbar arteries. Therefore, we performed DPSI assisted by cone beam
      CT in cases 1, 2. Six-month CT follow-up revealed no sign of sac enlargement by
      type II endoleak. 

PMID- 25844360
TI  - Transanal gauze packing to manage massive presacral bleeding secondary to
      prescral abscess caused by rectal anastomotic leakage: a novel approach.
AB  - Anastomotic leakage following rectal resection is a serious and fearful
      complication, and may cause presacral abscess and/or peritonitis. To our
      knowledge, massive hematochezia secondary to presacral abscess caused by
      anastomotic leakage has not yet been reported in the literature. We observed this
      rare and life-threatening complication in three patients who were successfully
      treated with a simple but effective transanal gauze packing technique. 

PMID- 25844361
TI  - Providing optimal regional care for ST-segment elevation myocardial infarction: a
      prospective cohort study of patients in the Hamilton Niagara Haldimand Brant
      Local Health Integration Network.
AB  - BACKGROUND: Although considered the evidence-based best therapy for ST-segment
      elevation myocardial infarction (STEMI), many patients do not receive primary
      percutaneous coronary intervention (PCI) because of health care resource
      distribution and constraints. This study describes the clinical management and
      outcomes of all patients identified with STEMI within a region, including those
      who did not receive primary PCI. METHODS: This study used a prospective cohort
      design. Patients presenting with STEMI to PCI- and non-PCI-capable hospitals in
      one integrated health region in Ontario were included in the study. The primary
      objective was to examine use of reperfusion strategies and timeliness of care.
      Secondary objectives included determining (through regression models) which
      variables were associated with mortality within 90 days, and describing patient
      uptake of risk-reducing therapies and activities post-STEMI. RESULTS: Between
      Apr. 1, 2010, and Mar. 31, 2013, data were collected on 2247 consecutive patients
      presenting with STEMI. Patients presenting to the PCI-capable hospital were more
      likely to receive primary PCI (82.5% v. 65.2%, p < 0.001) and be treated within
      optimal treatment times. However, there was no appreciable difference in
      mortality at 90 days post-STEMI between patients presenting to PCI- and non-PCI
      capable hospitals (7.8% v. 7.5%, p = 0.82), even after adjustment for acuity on
      presentation. Despite recognized risk factors, many patients were not taking
      evidence-based medications for risk factor modification before STEMI.
      INTERPRETATION: A systematic approach to regional STEMI care focusing on timely
      access to the best available therapies, rather than the type of reperfusion
      provided alone, can yield favourable outcomes.

PMID- 25844362
TI  - The effect of pharmacist-led medication review in high-risk patients in the
      emergency department: an evaluation protocol.
AB  - BACKGROUND: Adverse drug events are unintended and harmful events related to
      medication use. They are a leading cause of visits to the emergency department,
      unplanned admissions to hospital and death. Adverse drug events can be
      misdiagnosed in the emergency department, resulting in treatment delays. Our
      objective was to describe a process to evaluate the effect of pharmacist-led
      medication review in high-risk patients in the emergency department on the number
      of days these patients subsequently spent in hospital within 30 days of their
      index visit. METHODS: We describe the evaluation of a prospective multicentre
      quality improvement program. During the evaluation period, triage nurses will
      flag incoming patients to the emergency department at high risk for adverse drug
      events by applying a clinical decision rule consisting of 4 variables (comorbid
      conditions, antibiotic use within 7 days, medication changes within 28 days and
      age). Consecutive eligible patients will be enrolled in the study and
      systematically allocated to either a pharmacist-led medication review group or a
      control group. In the intervention group, pharmacists will collect best-possible
      medication histories, review the patient's medications for appropriateness and
      adverse drug events, and communicate the results of their medication review to
      patients, caregivers and physicians. In the control group, nurses will start
      medication reconciliation by collecting best-possible medication histories, and
      physicians will refer patients to onsite pharmacists for specific medication
      management questions as needed. Health outcomes will be assessed using anonymized
      data linkage to administrative health databases. The primary outcome will be the
      percent days spent in hospital over a 30-day period. INTERPRETATION: This
      protocol describes the methods for evaluating the effect of pharmacist-led
      medication review in high-risk patients in the emergency department on use of
      health services, and highlights the methodological challenges that will be
      encountered. We plan to disseminate the results of this evaluation through
      articles published in peer-reviewed journals, presentations at scientific
      meetings and briefing notes to institutional, provincial and national
      stakeholders.

PMID- 25844363
TI  - Patterns of health care use in a high-cost inpatient population in Ottawa,
      Ontario: a retrospective observational study.
AB  - BACKGROUND: A small proportion of patients account for the majority of health
      care spending. We used detailed clinical and administrative data to explore
      clinical characteristics, patterns of health care use and changes in cost
      profiles over time among high-cost inpatients in an acute tertiary care hospital
      in Ottawa, Ontario. METHODS: We identified all people who had 1 or more inpatient
      admissions to The Ottawa Hospital between Apr. 1, 2009, and Mar. 31, 2012. We
      calculated the direct inpatient costs using case-costing information to
      categorize patients into persistently high-cost, episodic high-cost and non-high
      cost groups. Within each group, we used discharge abstracts to measure encounter
      level characteristics and patterns of inpatient health care use over time. We
      also developed transition matrices to explore how inpatient costing states
      changed over time. RESULTS: During the study period, 100 178 patients had 132 996
      hospital admissions. Hospital spending was often limited to a single year for
      most of the patients (90.2%), with only a small proportion (7.4%) of patients
      remaining in the high-cost group in the subsequent year. Patients in the
      persistently (n = 236) and episodic (n = 5062) high-cost groups were often older,
      had medically complex conditions and generated most of the costs from nursing
      care and intensive care. Compared with patients in the other cost groups, those
      in the persistently high-cost group were more likely to have multiple
      readmissions (43.4%) and multiple placements in an alternate level of care
      (19.0%) and were high users of health care services outside of the hospital
      setting. INTERPRETATION: Hospital spending was often limited to a single year for
      most patients, and only a small proportion of patients remained in the high-cost
      group in the subsequent year. These persistently high-cost patients had medically
      complex conditions and often required expensive care. A greater understanding of
      the circumstances that result in persistent hospital spending remains an area for
      future work, including an exploration of the potential barriers impeding
      efficient transition out of acute care for high-risk patients.

PMID- 25844364
TI  - Dermatoses among returned Canadian travellers and immigrants: surveillance report
      based on CanTravNet data, 2009-2012.
AB  - BACKGROUND: There is a lack of multicentre analyses of the spectrum of
      dermatologic illnesses acquired by Canadian travellers and immigrants. Our
      objective for this study was to provide a comprehensive, Canada-specific
      surveillance summary of travel-related dermatologic conditions in a cohort of
      returned Canadian travellers and immigrants. METHODS: Data for Canadian
      travellers and immigrants with a primary dermatologic diagnosis presenting to
      CanTravNet sites between September 2009 and September 2012 were extracted and
      analyzed. Data were collected using the GeoSentinel data platform. This network
      comprises 56 specialized travel and tropical medicine clinics, including 6
      Canadian sites (Vancouver, Calgary, Toronto, Ottawa and Montreal), that
      contribute anonymous, de-linked, clinician- and questionnaire-based travel
      surveillance data on all ill travellers examined to a centralized Structure Query
      Language database. Results were analyzed according to reason for most recent
      ravel: immigration (including refugee); tourism; business;
      missionary/volunteer/research and aid work; visiting friends and relatives; and
      other, which included students, military personnel and medical tourists. RESULTS:
      During the study period, 6639 patients presented to CanTravNet sites across
      Canada and 1076 (16.2%) received a travel-related primary dermatologic diagnosis.
      Arthropod bites (n = 162, 21.5%), rash (n = 141, 18.7%), cutaneous larva migrans
      (n = 98, 13.0%), and skin and soft tissue infection (n = 92, 12.2%) were the most
      common dermatologic diagnoses or diagnostic bundles issued to returning Canadian
      tourists (n = 754, 70.1% of total sample). Patients travelling for the purpose of
      immigration (n = 63, 5.9%) were significantly more likely to require inpatient
      management of their dermatologic diagnoses (p < 0.001) than those travelling for
      other purposes. INTERPRETATION: This analysis of surveillance data details the
      spectrum of travel-related dermatological conditions among returning Canadian
      travellers in this cohort, and provides an epidemiologic framework for Canadian
      physicians encountering these patients.

PMID- 25844365
TI  - The development of guideline implementation tools: a qualitative study.
AB  - BACKGROUND: Research shows that guidelines featuring implementation tools
      (GItools) are more likely to be used than those without GItools, however few
      guidelines offer GItools and guidance on developing GItools is lacking. The
      objective of this study was to identify common processes and considerations for
      developing GItools. METHODS: Interviews were conducted with developers of 4 types
      of GItools (implementation, patient engagement, point-of-care decision-making and
      evaluation) accompanying guidelines on various topics created in 2008 or later
      identified in the National Guideline Clearinghouse. Participants were asked to
      describe the GItool development process and related considerations. A descriptive
      qualitative approach was used to collect and analyze data. RESULTS: Interviews
      were conducted with 26 GItool developers in 9 countries. Participants largely
      agreed on 11 broad steps, each with several tasks and considerations. Response
      variations identified issues lacking uniform approaches that may require further
      research including timing of GItool development relative to guideline
      development; decisions about GItool type, format and content; and whether and how
      to engage stakeholders. Although developers possessed few dedicated resources,
      they relied on partnerships to develop, implement and evaluate GItools.
      INTERPRETATION: GItool developers employed fairly uniform and rigorous processes
      for developing GItools. By supporting GItool development, the GItool methods
      identified here may improve guideline implementation and use.

PMID- 25844366
TI  - Chronic obstructive pulmonary disease in primary care: an epidemiologic cohort
      study from the Canadian Primary Care Sentinel Surveillance Network.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is mostly managed within
      primary care, but there is little Canadian evidence from this setting. This study
      was undertaken to determine the prevalence of physician-diagnosed COPD in primary
      care practices, and the degree of comorbidity with other chronic conditions, and
      to assess patterns of medication prescribing. METHODS: The Canadian Primary Care
      Sentinel Surveillance Network is a national "network of networks" whose member
      practices use electronic medical records (EMRs). At the time of the study, it
      included data from 444 physicians from 10 networks in 8 provinces. We conducted
      an epidemiologic cohort study of all patients who had EMR data collected by the
      network at the end of 2012. Validated case-finding algorithms were used to
      identify cases of COPD. We used descriptive statistics and multivariate modelling
      analyses to calculate the prevalence of COPD, its association with key
      demographic factors and comorbidities, and patterns of medication prescribing.
      RESULTS: The observed prevalence of COPD was 4.0% (10 043/250 346), which
      represents a population prevalence of 3.4% using age-sex standardization.
      Comorbidity was common, with prevalence ratios ranging from 1.1 for the presence
      of a single comorbid condition to 1.9 for 4 or more comorbid conditions.
      Anticholinergic agents (63%), short- (48%) and long-acting (38%) beta-agonists
      and inhaled corticosteroids (41%) were the most commonly used medications.
      INTERPRETATION: The prevalence of physician-diagnosed COPD in Canadian primary
      care practices was similar to that reported in other practice-based studies at
      about 3%-4%. Most patients had comorbid conditions and were taking multiple
      medications. EMR data may be useful to assess both the epidemiology and
      management of COPD in primary care practices.

PMID- 25844367
TI  - Prevention of overweight and obesity in children and youth: a systematic review
      and meta-analysis.
AB  - BACKGROUND: One-third of Canadian children are overweight or obese. This problem
      carries considerable concern for negative impacts on current and future health.
      Promoting healthy growth and development is critical. This review synthesized
      evidence on the effectiveness of behavioural interventions for preventing
      overweight and obesity in children and adolescents. METHODS: We updated the
      search of a previous Cochrane review. Five databases were searched up to August
      2013. Randomized trials of primary care-relevant behavioural (diet, exercise and
      lifestyle) interventions for preventing overweight and obesity in healthy normal-
      or mixed-weight children or youth aged 0-18 years were included if 12-week
      postbaseline data were provided for body mass index (BMI), BMI z-score, or
      prevalence of overweight or obesity. Any study reporting harms was included. Meta
      analyses were performed if possible. Features of interventions showing
      significant benefits were examined. RESULTS: Ninety studies were included, all
      with mixed-weight populations. Compared with controls, interventions showed a
      small but significant effect on BMI and BMI z-score (standardized mean difference
      -0.07, 95% confidence interval [CI] -0.10 to -0.03, I (2) = 74%), a reduction in
      BMI (mean difference -0.09 kg/m(2), 95% CI -0.16 to -0.03, I (2) = 76%) and a
      reduced prevalence of overweight and obesity (risk ratio [RR]; RRintervention -
      RRcontrol 0.94, 95% CI 0.89 to 0.99, I (2) = 0%; number needed to treat 51, 95%
      CI 29 to 289). Little evidence was available on harms. There was variability
      across efficacious interventions, although many of the interventions were short
      term, involved school-aged children and were delivered in educational settings.
      INTERPRETATION: Behavioural prevention interventions are associated with small
      improvements in weight outcomes in mixed-weight populations of children and
      adolescents. No intervention strategy consistently produced benefits.
      REGISTRATION: PROSPERO no. CRD42012002754.

PMID- 25844368
TI  - Treatment of overweight and obesity in children and youth: a systematic review
      and meta-analysis.
AB  - BACKGROUND: Childhood obesity is a public health concern. One-third of North
      American children and youth are overweight or obese. We reviewed the evidence of
      behavioural and pharmacological weight-management interventions on body mass
      index (BMI), BMI z-score and the prevalence of overweight and obesity in children
      and youth. METHODS: We updated the search of a previous review. We searched 4
      databases up to August 2013. We included randomized trials of primary care
      relevant behavioural (diet, exercise, lifestyle) and pharmacological (orlistat)
      interventions for treating overweight and obesity in children and youth aged 2-18
      years if 6-month post-baseline data were provided for BMI, BMI z-score or
      prevalence of overweight and obesity. In addition, we examined secondary health
      outcomes such as lipid and glucose levels, blood pressure, quality of life and
      physical fitness. We included any study reporting harms. We performed meta
      analyses when possible, and we examined the features of interventions that showed
      benefits. RESULTS: Thirty-one studies (29 behavioural, 2 pharmacological and
      behavioural) were included. Both intervention types showed a significant effect
      on BMI or BMI z-score in favour of treatment (behavioural: standardized mean
      difference [SMD] -0.54, 95% confidence interval [CI] -0.73 to -0.36; orlistat
      plus behavioural: SMD -0.43, 95% CI -0.60 to -0.25). Studies reported no
      significant difference between groups in the likelihood of reduced prevalence of
      overweight or overweight and obesity. Pooled estimates for blood pressure and
      quality of life showed significant benefits in favour of treatment (systolic
      blood pressure mean difference [MD] -3.42, 95% CI -6.65 to -0.29; diastolic blood
      pressure MD -3.39, 95% CI -5.17 to -1.60; quality of life MD 2.10, 95% CI 0.60 to
      3.60). Gastrointestinal difficulties were more common in youth taking orlistat
      than in the control group (risk ratio 3.77, 95% CI 2.56 to 5.55). We saw much
      variability across efficacious interventions. INTERPRETATION: Low- to moderate
      quality evidence suggests behavioural treatments are associated with a medium
      effect in terms of reduced BMI or BMI z-score compared with a small effect shown
      by combined pharmacological-behavioural interventions. Future research should
      evaluate active weight maintenance interventions in adolescents with longer
      follow-up and examine the effectiveness of combined pharmacological and
      behavioural interventions. REGISTRATION: PROSPERO no. CRD42012002754.

PMID- 25844369
TI  - Strategies for weight maintenance in adult populations treated for overweight and
      obesity: a systematic review and meta-analysis.
AB  - BACKGROUND: Once weight loss is achieved, the challenge is to maintain this
      benefit. This review reports on the effectiveness of programs for weight-loss
      maintenance, as part of a larger review examining treatments for overweight and
      obese adults. METHODS: We updated the search of a 2011 review on screening and
      management of overweight and obese adults. Four databases were searched. For
      inclusion, participants had to have lost weight in treatment and then been
      randomly assigned to a weight-maintenance intervention or control conditions.
      Studies from the 2011 review that met the criteria were included. Data were
      extracted and pooled (where possible) for outcomes related to weight-loss
      maintenance. RESULTS: Eight studies were included. Compared with control
      participants, intervention participants regained less weight (mean difference
      [MD] -1.44 kg, 95% confidence interval [CI] -2.42 to -0.47), regardless of
      whether the intervention was behavioural (MD-1.56 kg, 95% CI -3.10 to -0.02) or
      pharmacologic plus behavioural (MD -1.39 kg, 95% CI -2.86 to 0.08). Intervention
      participants also showed better weight maintenance than the control participants
      in terms of waist circumference (MD -2.30 cm, 95% CI -3.45 to -1.15) and body
      mass index (MD -0.95 kg/m(2), 95% CI -1.67 to -0.23). Participants undergoing
      pharmacologic plus behavioural interventions were more likely to maintain a loss
      of 5% or more of initial body weight than those in the control group (risk ratio
      [RR] 1.33, 95% CI 1.15 to 1.54); no difference was found for maintaining a weight
      loss of 10% or more (RR 1.76, 95% CI 0.75 to 4.12). INTERPRETATION: Moderate
      quality evidence shows that overweight and obese adults can benefit from
      interventions for weight maintenance following weight loss. However, there is
      insufficient evidence on the long-term sustainability of these benefits.
      REGISTRATION: PROSPERO no. CRD42012002753.

PMID- 25844370
TI  - Neonatal opioid withdrawal and antenatal opioid prescribing.
AB  - BACKGROUND: The incidence of neonatal opioid withdrawal is increasing in both
      Canada and the United States. However, the degree to which the treatment of pain
      with opioids, rather than the misuse of prescription opioids or heroin,
      contributes to the prevalence of neonatal opioid withdrawal remains unknown.
      METHODS: We conducted a retrospective, population-based, cross-sectional study
      between 1992 and 2011 in Ontario with 2 objectives. First, we determined the
      annual incidence of neonatal abstinence syndrome. Second, using data from a
      subset of women eligible for publicly funded prescription drugs, we determined
      what proportion of women who deliver an infant with neonatal abstinence syndrome
      were given a prescription for an opioid before and during pregnancy. RESULTS: The
      incidence of neonatal abstinence syndrome in Ontario increased 15-fold during the
      study period, from 0.28 per 1000 live births in 1992 to 4.29 per 1000 live births
      in 2011. During the final 5 years of the study, we identified 927 deliveries of
      infants with neonatal abstinence syndrome to mothers who were public drug plan
      beneficiaries. Of these mothers, 67% had received an opioid prescription in the
      100 days preceding delivery, including 53.3% who received methadone, an increase
      from 28.6% in the interval spanning 1 to 2 years before delivery (p < 0.001).
      Prescription for nonmethadone opioids decreased from 38% to 17% (p < 0.001).
      INTERPRETATION: The incidence of neonatal opioid withdrawal in Ontario has
      increased substantially over the last 20 years. Most of the women in this cohort
      who delivered an infant with neonatal abstinence syndrome had received a
      prescription for an opioid both before and during their pregnancy.

PMID- 25844371
TI  - Acceptability and yield of birth-cohort screening for hepatitis C virus in a
      Canadian population being screened for colorectal cancer: a cross-sectional
      study.
AB  - BACKGROUND: Screening for hepatitis C virus (HCV) is recommended in patients born
      between 1945 and 1965 ("baby boomers") in the United States. Because these
      patients are often screened for colorectal cancer, dual screening for HCV may
      enhance case identification. Our objectives were to assess the acceptability and
      yield of screening for HCV among patients undergoing screening for colorectal
      cancer. METHODS: Patients referred for a colonoscopy to screen for colorectal
      cancer completed an anonymous survey regarding the acceptability of screening for
      HCV, risk factors and prior testing. The impacts of demographics and risk factors
      for HCV on willingness to be screened were determined using logistic regression,
      and the stored sera of 483 patients who had undergone screening for colorectal
      cancer between February 2011 and August 2012 were tested for HCV antibodies.
      RESULTS: Among 1012 survey respondents (median age 56 yr; 911 [90.0%] were baby
      boomers, 880 [87.0%] were white and 223 [22.0%] were born outside Canada), 123
      patients (12.2%) reported prior testing for HCV. HCV was previously diagnosed in
      9 of these patients (0.9%, representing 1.0% of the patients who were baby
      boomers): 5 (55.6% of those diagnosed) reported risk factors. Excluding patients
      diagnosed with HCV, 903 (90.0%) respondents indicated that they would consent to
      testing of blood or saliva for HCV. After adjusting for age, sex and status of
      immigration, patients who were white (odds ratio [OR] 3.38, 95% confidence
      interval [CI] 1.81-6.32) and patients with risk factors (> 1 v. 0: OR 3.67, 95%
      CI 1.12-12.02) had a greater acceptance of screening. Among 483 patients screened
      for colorectal cancer, 3 were anti-HCV positive (0.6%, 95% CI 0.1%-1.8%),
      representing 0.8% (95% CI 0.2%-2.4%) of the patients who were baby boomers.
      INTERPRETATION: Acceptance of screening for HCV is high among patients undergoing
      screening for colorectal cancer in the Calgary area. However, the low prevalence
      of HCV suggests that the cost-effectiveness of birth-cohort screening in this
      population warrants evaluation.

PMID- 25844372
TI  - Effect of pediatric palliative care programs on health care resource utilization
      and costs among children with life-threatening conditions: a systematic review of
      comparative studies.
AB  - BACKGROUND: Pediatric palliative care is a relatively new and evolving field, and
      the cost of pediatric palliative care programs is unclear. We conducted a
      systematic review to compare inpatient health care utilization and costs among
      children with life-threatening conditions who have accessed a pediatric
      palliative care program and those who have not. METHODS: We searched MEDLINE,
      Embase, CINAHL and LILACS databases from January 2000 to July 2013, as well as
      the grey literature, for experimental or observational studies that compared
      pediatric palliative care programs with usual care. Outcomes of interest included
      hospital admissions, length of stay and health care costs. RESULTS: Of the 5193
      records identified, we reviewed 109 in full and included 11 in our study. The
      overall quality of the studies was moderate to low. We observed mixed results for
      all outcomes. Compared with patients receiving usual care, fewer patients in the
      palliative care group had hospital admissions and fewer of those with cancer had
      planned hospital admissions. In contrast, no effects were observed regarding the
      overall number of hospital, emergency or outpatient admissions. Conflicting
      results were observed with regards to critical care utilization. Studies showed a
      trend toward shorter lengths of stay in hospital in the palliative care group.
      However, a single study that also considered inpatient time in hospice facilities
      found an increase in total length of stay, which showed a shift in the setting of
      health care utilization. We observed no conclusive trend in the effects on cost.
      INTERPRETATION: Evidence suggests that pediatric palliative care programs may
      result in a shift of utilization to other health care settings beyond hospital
      care. These settings should be considered when measuring resource utilization and
      costs.

PMID- 25844373
TI  - Prevalence and management of hypertension in primary care practices with
      electronic medical records: a report from the Canadian Primary Care Sentinel
      Surveillance Network.
AB  - BACKGROUND: Most epidemiologic reports on hypertension in Canada are based on
      data from surveys or on administrative data. We report on the prevalence and
      management of hypertension based on data from the Canadian Primary Care Sentinel
      Surveillance Network (CPCSSN), which consists of validated, national, point-of
      care data from primary care practices. METHODS: We included CPCSSN data as of
      Dec. 31, 2012, for patients 18 years and older who had at least 1 clinical
      encounter during the previous 2 years with one of the 444 family physicians and
      nurse-practitioners who participate in the CPCSSN. We calculated the prevalence
      of hypertension, the proportion of patients who achieved blood pressure targets,
      the number of encounters with primary care providers, comorbidities and
      pharmacologic management. RESULTS: Of the 250 346 patients who met the
      eligibility criteria, 57 180 (22.8%) had a diagnosis of hypertension. Of the 44
      981 patients for whom blood pressure data were available, 35 094 (78.0%) had
      achieved both targets for systolic (<=?140 mm Hg) and diastolic (<=?90 mm Hg)
      pressure. Compared with patients who did not have a hypertension diagnosis, those
      with hypertension were significantly more likely to have a comorbidity and
      visited their primary care provider more often. Among the patients with
      hypertension, 12.1% were not taking antihypertensive medications; nearly two
      thirds (61.7%) had their condition controlled with 1 or 2 drugs. INTERPRETATION:
      The prevalence of hypertension based on CPCSSN data was similar to estimates from
      the Canadian Health Measures Survey. Although achievement of blood pressure
      targets was high, patients with hypertension had more comorbidities and saw their
      primary care provider more often than those without hypertension.

PMID- 25844374
TI  - Secular trends in end-stage renal disease requiring dialysis in Manitoba, Canada:
      a population-based study.
AB  - BACKGROUND: End-stage renal disease (ESRD) requiring dialysis is expensive and is
      associated with disproportionately poor health outcomes and quality of life.
      Understanding regional long-term secular trends in the incidence and prevalence
      of dialysis will allow for the alignment of appropriate and efficient delivery of
      care. The primary objective of this study was to describe long-term secular and
      geographic trends in ESRD over a 22-year period in a single-provider Canadian
      health care setting. METHODS: Using a previously validated case definition, we
      described the annual incidence and prevalence of ESRD in Manitoba from 1989 to
      2010, stratified by age, sex and geographic location within the province.
      RESULTS: We searched more than 1.2 million records within the Manitoba Health
      repository. We identified 9489 patients in the Manitoba Health Physician Claims
      database with at least 1 claim for dialysis from 1989 through Mar. 31, 2010.
      Using the case definition of any 2 dialysis treatment claims, the total annual
      incidence of ESRD increased 2.5-fold from 15.8 to 40.2 per 100 000 during the
      study period. Of note, the northern rural portions of the province saw a 12-fold
      unadjusted increase in ESRD, from 8.1 per 100 000 in 1989 to 96.3 per 100 000 in
      2009. INTERPRETATION: The incidence and prevalence of ESRD is increasing in
      Manitoba, most notably in the north of the province. Innovative interventions,
      such as primary screening and treatment initiatives, should specially target
      northern rural regions.

PMID- 25844375
TI  - Deaths from exposure to paramethoxymethamphetamine in Alberta and British
      Columbia, Canada: a case series.
AB  - BACKGROUND: Paramethoxymethamphetamine (PMMA) is a ring-substituted amphetamine
      similar in structure to 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy"),
      but substantially more toxic. We describe the clinical features of fatal
      exposures in the provinces of Alberta and British Columbia, Canada. METHODS: We
      conducted a retrospective case series on deaths in Alberta and BC between June
      2011 and April 2012 for which forensic toxicologic analysis was positive for PMMA
      and the drug was implicated as the primary toxic agent. Data collected included
      patient demographics, exposure history, clinical features, investigations,
      therapy provided and postmortem toxicologic findings. RESULTS: A total of 27 PMMA
      associated deaths (20 in Alberta, 7 in BC) were reported in the 11-month period.
      The median age was 24 (range 14-52) years, and 22 (81%) were male. Ten patients
      were pronounced dead at the scene, and 17 died in hospital. The median time from
      exposure to death was 17 (range 5-264) hours. The median first-recorded vital
      signs (and ranges) were: heart rate 160 (86-201) beats/min, blood pressure 89/43
      (69/30-162/83) mm Hg, respiratory rate 40 (26-48) breaths/min, oxygen saturation
      81% (68%-100%) and temperature 39.4 degrees C (34-43.8 degrees C). Sixteen of the
      17 people who died in hospital presented with clinical features consistent with
      serotonin syndrome. End-organ dysfunction included hepatic (30%) and acute kidney
      injury (85%), rhabdomyolysis (54%), coagulopathy (61%) and cardiac ischemia
      (15%). Other drugs identified on toxicologic analysis were MDMA (n = 27), cocaine
      or its metabolite benzoylecgonine (n = 14) and methamphetamine (n = 12).
      INTERPRETATION: Exposure to PMMA was characterized by multiorgan dysfunction and
      serotonin syndrome, followed by cardiovascular collapse. In addition to PMMA,
      multiple synthetic amphetamines were present on toxicologic analysis. When
      evaluating patients suspected of exposure to sympathomimetic drugs of abuse,
      clinicians must anticipate multiple clinical effects from the increased release
      of dopamine, serotonin, norepinephrine and other neurotransmitters.

PMID- 25844376
TI  - Patterns of use for brand-name versus generic oral bisphosphonate drugs in
      Ontario over a 13-year period: a descriptive study.
AB  - BACKGROUND: Bisphosphonates are the first-line therapy for the treatment of
      osteoporosis. In the province of Ontario, the Ontario Drug Benefit Program funds
      medications for patients aged 65 years and older. The Ontario Drug Benefit
      Program has a generic substitution policy that requires lower-cost generic drugs
      to be dispensed when they are available. However, there is controversy
      surrounding the efficacy and tolerability of generic bisphosphonates. The
      objective of this study was to describe patterns in the use of brand-name versus
      generic formulations when dispensing oral bisphosphonate over a 13-year period.
      METHODS: We identified all osteoporotic preparations for alendronate and
      risedronate that were dispensed through the Ontario Drug Benefit Program from
      2001 to 2014. We stratified our sample into community-dwelling residents and
      residents in long-term care facilities. The number of prescriptions dispensed per
      month were plotted to illustrate trends over time. RESULTS: We found a rapid
      switch from brand-name to generic bisphosphonate equivalents immediately after
      the generic became available on the Ontario Drug Benefit formulary, with generics
      accounting for > 88% of dispensed drug within 2 months. We also observed a
      reduction in the number of generic drugs dispensed each time a new brand-name
      alternative (e.g., monthly risedronate, weekly alendronate plus vitamin D) was
      introduced to the formulary. The dispensing trends were similar in the community
      and long-term care settings. INTERPRETATION: The Ontario Drug Benefit Program
      generic substitution policy resulted in rapid uptake of generic oral
      bisphosphonates among seniors in Ontario. However, there was a switch away from
      generic medications to new brand-name alternatives whenever they were introduced
      to the formulary. Therefore, some patients continued to use brand-name
      bisphosphonate despite the availability of generic options.

PMID- 25844377
TI  - Chronic health conditions reported by male inmates newly admitted to Canadian
      federal penitentiaries.
AB  - BACKGROUND: International health studies have shown that inmates have higher
      rates of infectious diseases, chronic diseases and psychiatric disorders relative
      to the general population. We conducted a systematic collection of data on
      chronic physical health conditions reported by newly admitted inmates in Canadian
      federal penitentiaries. METHODS: Over a 6-month period from April to September
      2012, we collected and analyzed data from a standardized health interview
      routinely conducted with consenting incoming male inmates (n = 2273). Prevalence
      rates of health conditions were determined and disaggregated by age (< 50 yr and
      >= 50 yr) and by Aboriginal status. RESULTS: The most common health conditions
      reported by respondents were head injury (34.1%), back pain (19.3%), asthma
      (14.7%) and hepatitis C virus (HCV) infection (9.4%). Rates of many health
      conditions were higher among inmates 50 years of age or older than among younger
      inmates. Compared with their non-Aboriginal counterparts, Aboriginal inmates had
      higher rates of head injury and HCV infection. INTERPRETATION: Our study provides
      a benchmark that can be used to examine health trends within Canada's federal
      penitentiaries over time and points to subgroups of newly admitted inmates for
      whom health services may need to be concentrated.

PMID- 25844378
TI  - Stroke Recovery: Surprising Influences and Residual Consequences.
AB  - There is startling individual variability in the degree to which people recover
      from stroke, and the duration of time over which recovery of some symptoms occur.
      There are a variety of mechanisms of recovery from stroke, which take place at
      distinct time points after stroke and are influenced by different variables. We
      review recent studies from our laboratory that unveil some surprising findings,
      such as the role of education in chronic recovery. We also report data showing
      that the consequences that most plague survivors of stroke and their caregivers
      are not dependence in activities of daily living, but loss of more high level
      functions, such as empathy or written language. These results have implications
      for rehabilitation and management of stroke.

PMID- 25844379
TI  - The experience of implementing the board of trustees' policy in teaching
      hospitals in Iran: an example of health system decentralization.
AB  - BACKGROUND: In 2004, the health system in Iran initiated an organizational reform
      aiming to increase the autonomy of teaching hospitals and make them more
      decentralized. The policy led to the formation of a board of trustees in each
      hospital and significant modifications in hospitals' financing. Since the reform
      aimed to improve its predecessor policy (implementation of hospital autonomy
      began in 1995), it expected to increase user satisfaction, as well as enhance
      effectiveness and efficiency of healthcare services in targeted hospitals.
      However, such expectations were never realized. In this research, we explored the
      perceptions and views of expert stakeholders as to why the board of trustees'
      policy did not achieve its perceived objectives. METHODS: We conducted 47 semi
      structured face-to-face interviews and two focus group discussions (involving 8
      and 10 participants, respectively) with experts at high, middle, and low levels
      of Iran's health system, using purposive and snowball sampling. We also collected
      a comprehensive set of relevant documents. Interviews were transcribed verbatim
      and analyzed thematically, following a mixed inductive-deductive approach.
      RESULTS: Three main themes emerged from the analysis. The implementation approach
      (including the processes, views about the policy and the links between the policy
      components), using research evidence about the policy (local and global), and
      policy context (health system structure, health insurers capacity, hospitals'
      organization and capacity and actors' interrelationships) affected the policy
      outcomes. Overall, the implementation of hospital decentralization policies in
      Iran did not seem to achieve their intended targets as a result of assumed
      failure to take full consideration of the above factors in policy implementation
      into account. CONCLUSION: The implementation of the board of trustees' policy did
      not achieve its desired goals in teaching hospitals in Iran. Similar
      decentralization policies in the past and their outcomes were overlooked, while
      the context was not prepared appropriately and key stakeholders, particularly the
      government, did not support the decentralization of Iran's health system.

PMID- 25844380
TI  - Why and how is compassion necessary to provide good quality healthcare?
AB  - Recent disclosures of failures of care in the National Health Service (NHS) in
      England have led to debates about compassion deficits disallowing health
      professionals to provide high quality responsive care. While the link between
      high quality care and compassion is often taken for granted, it is less obvious
      how compassion - often originating in the individual's emotional response - can
      become a moral sentiment and lead to developing a system of norms and values
      underpinning ethics of care. In this editorial, I argue why and how compassion
      might become a foundation of ethics guiding health professionals and a basis for
      ethics of care in health service organisations. I conclude by discussing a recent
      case of prominent healthcare failure in the NHS to highlight the relationship
      between compassion as an aspect of professional ethics on the one hand, and
      values and norms that institutions and specific policies promote on the other
      hand. 

PMID- 25844381
TI  - Improving the world's health through the post-2015 development agenda:
      perspectives from Rwanda.
AB  - The world has made a great deal of progress through the Millennium Development
      Goals (MDGs) to improve the health and well-being of people around the globe, but
      there remains a long way to go. Here we provide reflections on Rwanda's
      experience in working to meet the health-related targets of the MDGs. This
      experience has informed our proposal of five guiding principles that may be
      useful for countries to consider as the world sets and moves forward with the
      post-2015 development agenda. These include: 1) advancing concrete and meaningful
      equity agendas that drive the post-2015 goals; 2) ensuring that goals to meet
      Universal Health Coverage (UHC) incorporate real efforts to focus on improving
      quality and not only quantity of care; 3) bolstering education and the internal
      research capacity within countries so that they can improve local evidence-based
      policy-making; 4) promoting intersectoral collaboration to achieve goals, and 5)
      improving collaborations between multilateral agencies - that are helping to
      monitor and evaluate progress towards the goals that are set - and the countries
      that are working to achieve improvements in health within their nation and across
      the world. 

PMID- 25844382
TI  - Patients attitude towards surgeons attire in Our Lady of Lourdes Hospital
      Drogheda.
AB  - BACKGROUND: A doctor's competence and professionalism is often judged on the
      basis of attire. Our Lady of Lourdes (OLOL) is a leading Irish hospital in the
      implementation of Bare Below the Elbows (BBTE) policy, however surgical attire is
      not standardised and there is great variability in attire worn on wards. We aimed
      to evaluate patients attitude towards surgeons attire in OLOL. METHODS: A
      prospective survey of adult surgical in-patients was conducted from October 2013
      to February 2014. A twelve-question questionnaire was used as data collection
      tool, using a five point Likert scale to assess patients response to each
      question. Data were collected on patient demographics, patients level of trust
      and confidence based on different surgical attire, and patients perception of
      different attire worn by surgical teams. RESULTS: There were 150 completed
      surveys during the study period with a male to female ratio of 44% to 56%
      respectively. The mean patient length of in-hospital stay (LOS) was 4.7 days
      (range 1-22). The most commonly represented age group was 30-40 years (18%), with
      a comparable spread among all age groups. The majority of patients found the
      attire worn by surgeons on the ward to be very appropriate (93%). Majority of
      responders believed scrubs to be the most appropriate attire for surgeons on
      wards (39%), followed by shirt and tie with white coat (38%) followed by short
      sleeved shirt and no tie (18%). Shirt and tie with white coat had a positive
      effect on patients trust in 63% of responders, a negative effect in 10% and no
      effect in 26%. Scrubs had a positive effect on patients trust in 63%, negative
      effect in 11% and no effect in 25%. Short sleeved shirt and no tie had a positive
      effect in 44%, negative effect in 25% and no effect in 30% of patients.
      CONCLUSION: Patients in OLOL find attire worn by surgeons to be appropriate.
      Shirt and tie with white coat or scrubs remains the patient's choice attire for
      surgeons. Shirt and tie with white coat or scrubs has a more positive effect on
      trust of patients compared to short sleeved shirt and no tie.

PMID- 25844383
TI  - Exploring cigarette use among male migrant workers in Nigeria.
AB  - BACKGROUND: There is limited knowledge about the use of cigarettes by blacks
      outside the United States (U.S). Nigeria creates an opportunity to explore
      smoking behaviours, smoking cessation (nicotine dependence) and use of cigarettes
      in a country that has a large black population outside the U.S. METHODS: We
      conducted three Focus Group Discussions (FGDs) involving twenty-four male migrant
      workers who reported that they were current cigarette smokers. Interviews were
      audio-taped and transcribed. RESULTS: Four major themes namely: reasons for
      initiating and continuing to smoke cigarettes, factors affecting brand choice,
      barriers to quitting, effect of smoking mentholated cigarette brands were
      identified. CONCLUSION: This study provides insight into the use of mentholated
      and non-mentholated cigarettes and suggests the need for further studies to
      explore smoking behavior among Nigerians.

PMID- 25844384
TI  - Knowledge and attitude toward smoke-free legislation and second-hand smoking
      exposure among workers in indoor bars, beer parlors and discotheques in Osun
      State of Nigeria.
AB  - BACKGROUND: One of the requirements of the Osun State smoke-free legislation is
      to ensure smoke-free enclosed and partially enclosed workplaces. This survey was
      conducted to assess the knowledge and attitude of workers in indoor bars, beer
      parlors and discotheques to smoke-free legislation in general and the Osun State
      smoke-free law in particular. METHODS: A convenience sampling of 36 hospitality
      centers was conducted. Interviewer-administered questionnaires were used to
      elicit responses about the objectives from non-smoking workers. The
      questionnaires had sections on knowledge of the Osun State smoke-free law,
      attitude toward the law and smoke-free legislation in general and exposure to
      second-hand tobacco smoke by the workers. Questions were also asked about the
      second-hand tobacco smoking status of these workers. The data were analyzed using
      SPSS version 15.0. RESULTS: We had 154 participants recruited into the study.
      There were 75 males (48.0%) and 79 females (52.0%). On the overall, respondents
      had a good knowledge of the effects of second-hand smoke on health (70.2%) with
      75.0% of them being aware of the general smoke-free law and 67.3% being aware of
      the Osun State smoke-free law although none of them had ever seen a copy of the
      law. A high proportion (60.0%) was in support of the Osun smoke-free law although
      all of them think that the implementation of the law could reduce patronage and
      jeopardize their income. Attitude toward second-hand smoking was generally
      positive with 72.0% of them having no tolerance for second-hand tobacco smoke in
      their homes. Most participants (95.5%) had been exposed to tobacco smoke in the
      workplace within the past week. CONCLUSION: Despite the high level of awareness
      of the respondents about the dangers of second hand smoke and their positive
      attitude to smoke-free laws, nearly all were constantly being exposed to second
      hand smoke at work. This calls for policy level interventions to improve the
      implementation of the smoke-free law.

PMID- 25844386
TI  - Medical sociology as a heuristic instrument for medical tourism and cross-border
      healthcare: Comment on "International patients on operation vacation -
      perspectives of patients travelling to Hungary for orthopedic treatments".
AB  - In this commentary, we establish a relationship between medical sociology and the
      study of medical tourism and cross-border healthcare by introducing Ronald
      Andersen's behavioral model of healthcare use, and linking this model to the
      recent empirical study of Kovacs et al. on patients travelling to Hungary for
      orthopedic treatment. Finally, we plead for more measurement in the field of
      patient mobility. 

PMID- 25844385
TI  - Substitutes or complements? Diagnosis and treatment with non-conventional and
      conventional medicine.
AB  - BACKGROUND: Portugal has a strong tradition of conventional western healthcare.
      So it provides a natural case study for the relationship between
      Complementary/Alternative Medicine (CAM) and Western Medicine (WM). This work
      aims to test the relationship between CAM and WM users in the diagnosis and
      treatment stages and to estimate the determinants of CAM choice. METHODS: The
      forth Portuguese National Health Survey is employed to estimate two single probit
      models and obtain the correlation between the consumption of CAM and WM medicines
      in the diagnosis and treatment stages. RESULTS: Firstly, both in the diagnosis
      and the treatment stage, CAM and WM are seen to be complementary choices for
      individuals. Secondly, self-medication also shows complementarity with the choice
      of CAM treatment. Thirdly, education has a non-linear relationship with the
      choice of CAM. Finally, working status, age, smoking and chronic disease are
      determinant factors in the decision to use CAM. CONCLUSION: The results of this
      work are relevant to health policy-makers and for insurance companies. Patients
      need freedom of choice and, for the sake of safety and efficacy of treatment, WM
      and CAM healthcare ought to be provided in a joint and integrated health system.

PMID- 25844387
TI  - Time to shift from systems thinking-talking to systems thinking-action: Comment
      on "Constraints to applying systems thinking concepts in health systems: A
      regional perspective from surveying stakeholders in Eastern Mediterranean
      countries".
AB  - A recent International Journal of Health Policy and Management (IJHPM) article by
      Fadi El-Jardali and colleagues makes an important contribution to the literature
      on health system strengthening by reporting on a survey of healthcare
      stakeholders in Low- and Middle-Income Countries (LMICs) about Systems Thinking
      (ST). The study's main contributions are its confirmation that healthcare
      stakeholders understand the importance of ST but do not know how to act on that
      understanding, and the call for collective action by the global community of
      systems thinkers committed to healthcare improvement. We offer three basic
      considerations for next steps by this community, derived from our recent work in
      ST and the related field of Knowledge Translation (KT): resist the temptation to
      adopt a reductionist approach; recognize not everyone needs to understand ST; and
      do not wait for everything to be in place before getting started. 

PMID- 25844388
TI  - Whither mental health policy-where does it come from and does it go anywhere
      useful?: Comment on "Cross-national diffusion of mental health policy".
AB  - Factors influencing cross-national diffusion of mental health policy are
      important to understand but complex to research. This commentary discusses Shen's
      research study on cross-national diffusion of mental health policy; examines the
      extent to which the three questions researched by Shen (whether countries are
      more likely to have a mental health policy (a) the earlier a country becomes a
      member of World Health Organization (WHO), (b) the more international aid a
      country receives, and (c) the more neighbouring countries already have a mental
      health policy) are in fact able to assess WHO's impact on cross-national
      diffusion of mental health policy. The commentary then suggests a range of more
      specific questions which may be used to further elucidate the impact of WHO on an
      individual country, and considers the relative value of published mental health
      policy compared with the integration of mental health into national health sector
      strategies and other sector reforms, and concludes with a call for more
      integration of mental health across all WHO activities at international, regional
      and country levels. 

PMID- 25844389
TI  - The changing National Health Service: market-based reform and morality: Comment
      on "Morality and Markets in the NHS".
AB  - This commentary explores some of the issues raised by Gilbert et al. short
      communication, Morality and Markets in the NHS. The increasing role of market
      mechanisms and the changing types of healthcare providers together with the use
      of choice and competition to drive improvements in quality in the National Health
      Service (NHS), all have important ethical implications. In order for the NHS to
      continue providing the level of service quality that out performs many high
      income countries, despite spending much less on healthcare, we need a re-think of
      creeping marketization and privatisation and a consolidation of the NHS as a
      publically owned resource run for the benefit of patients and the public, not
      commercial interests. 

PMID- 25844390
TI  - Revealing power in truth: Comment on "Knowledge, moral claims and the exercise of
      power in global health".
AB  - Jeremy Shiffman's editorial appropriately calls on making all forms of power more
      apparent and accountable, notably productive power derived from expertise and
      claims to moral authority. This commentary argues that relationships based on
      productive power can be especially difficult to reveal in global health policy
      because of embedded notions about the nature of power and politics. Yet, it is
      essential to recognize that global health is shot through with power
      relationships, that they can take many forms, and that their explicit
      acknowledgement should be part of, rather than factored out of, any reform of
      global health governance. 

PMID- 25844391
TI  - Going beyond the hero in leadership development: the place of healthcare context,
      complexity and relationships: Comment on "Leadership and leadership development
      in healthcare settings - a simplistic solution to complex problems?".
AB  - There remains a conviction that the torrent of publications and the financial
      outlay on leadership development will create managers with the skills and
      characters of perfect leaders, capable of guiding healthcare organisations
      through the challenges and crises of the 21st century. The focus of much
      attention continues to be the search for the (illusory) core set of heroic
      qualities, abilities or competencies that will enable the development of leaders
      to achieve levels of supreme leadership and organisational performance. This
      brief commentary adds support to McDonald's (1) call for recognition of the
      complexity of the undertaking. 

PMID- 25844393
TI  - Pain-Related Fear, Disability, and the Fear-Avoidance Model of Chronic Pain.
AB  - Chronic pain is a significant public health concern that imposes substantial
      burdens on individuals and healthcare systems, and factors that contribute to the
      development and maintenance of pain-related disability are of increasing
      empirical and clinical interest. Consistent with the fear-avoidance model of
      chronic pain, greater pain-related fear has consistently been associated with
      more severe disability and may predict the progression of disability over time.
      Recent evidence indicates that treatments designed to reduce pain-related fear
      are efficacious for improving disability outcomes, and several clinical trials
      are currently underway to test tailored intervention content and methods of
      dissemination. Future research in this area is needed to identify factors (e.g.,
      substance use, comorbid psychopathology) that may influence interrelations
      between pain-related fear, response to treatment, and disability.

PMID- 25844392
TI  - Anti-Neoplastic Cytotoxicity of Gemcitabine-(C4-amide)-[anti-EGFR] in Dual
      combination with Epirubicin-(C3-amide)-[anti-HER2/neu] against Chemotherapeutic
      Resistant Mammary Adenocarcinoma (SKBr-3) and the Complementary Effect of
      Mebendazole.
AB  - AIMS: Delineate the feasibility of simultaneous, dual selective "targeted"
      chemotherapeutic delivery and determine if this molecular strategy can promote
      higher levels anti-neoplastic cytotoxicity than if only one covalent
      immunochemotherapeutic is selectively "targeted" for delivery at a single
      membrane associated receptor over-expressed by chemotherapeutic-resistant mammary
      adenocarcinoma. METHODOLOGY: Gemcitabine and epirubicin were covalently bond to
      anti-EGFR and anti-HER2/neu utilizing a rapid multi-phase synthetic organic
      chemistry reaction scheme. Determination that 96% or greater gemcitabine or
      epirubicin content was covalently bond to immunoglobulin fractions following size
      separation by micro-scale column chromatography was established by methanol
      precipitation analysis. Residual binding-avidity of gemcitabine-(C4-amide)-[anti
      EG-FR] applied in dual-combination with epirubicin-(C3-amide)-[anti-HER2/neu] was
      determined by cell-ELIZA utilizing chemotherapeutic-resistant mammary
      adenocarcinoma (SKBr-3) populations. Lack of fragmentation or polymerization was
      validated by SDS-PAGE/immunodetection/chemiluminescent autoradiography. Anti
      neoplastic cytotoxic potency was determined by vitality stain analysis of
      chemotherapeutic-resistant mammary adenocarcinoma (SKBr-3) monolayers known to
      uniquely over-express EGFR (2 * 105/cell) and HER2/neu (1 * 106/cell) receptor
      complexes. The covalent immunochemotherapeutics gemcitabine-(C4-amide)-[anti
      EGFR] and epirubicin-(C3-amide)-[anti-HER2/neu] were applied simultaneously in
      dual-combination to determine their capacity to collectively evoke elevated
      levels of anti-neoplastic cytotoxicity. Lastly, the tubulin/microtubule inhibitor
      mebendazole evaluated to determine if it's potential to complemented the anti
      neoplastic cytotoxic properties of gemcitabine-(C4-amide)-[anti-EGFR] in dual
      combination with epirubicin-(C3-amide)-[anti-HER2/neu]. RESULTS: Dual-combination
      of gemcitabine-(C4-amide)-[anti-EGFR] with epirubicin-(C3-amide)-[anti-HER2/neu]
      produced greater levels of anti-neoplastic cytotoxicity than either of the
      covalent immunochemotherapeutics alone. The benzimidazole microtubule/tubulin
      inhibitor, mebendazole complemented the anti-neoplastic cytotoxicity of
      gemcitabine-(C4-amide)-[anti-EGFR] in dual-combination with epirubicin-(C3-amide)
      [anti-HER2/neu]. CONCLUSIONS: The dual-combination of gemcitabine-(C4-amide)
      [anti-EGFR] with epirubicin-(C3-amide)-[anti-HER2/neu] produced higher levels of
      selectively "targeted" anti-neoplastic cytotoxicity against chemotherapeutic
      resistant mammary adenocarcinoma (SKBr-3) than either covalent
      immunochemotherapeutic alone. The benzimidazole tubulin/microtubule inhibitor,
      mebendazole also possessed anti-neoplastic cytotoxicity against chemotherapeutic
      resistant mammary adenocarcinoma (SKBr-3) and complemented the potency and
      efficacy of gemcitabine-(C4-amide)-[anti-EGFR] in dual-combination with
      epirubicin-(C3-amide)-[anti-HER2/neu].

PMID- 25844394
TI  - Cost-effectiveness of community-based strategies to strengthen the continuum of
      HIV care in rural South Africa: a health economic modelling analysis.
AB  - BACKGROUND: Home HIV counselling and testing (HTC) achieves high coverage of
      testing and linkage to care compared with existing facility-based approaches,
      particularly among asymptomatic individuals. In a modelling analysis we aimed to
      assess the effect on population-level health and cost-effectiveness of a
      community-based package of home HTC in KwaZulu-Natal, South Africa. METHODS: We
      parameterised an individual-based model with data from home HTC and linkage field
      studies that achieved high coverage (91%) and linkage to antiretroviral therapy
      (80%) in rural KwaZulu-Natal, South Africa. Costs were derived from a linked
      microcosting study. The model simulated 10,000 individuals over 10 years and
      incremental cost-effectiveness ratios were calculated for the intervention
      relative to the existing status quo of facility-based testing, with costs
      discounted at 3% annually. FINDINGS: The model predicted implementation of home
      HTC in addition to current practice to decrease HIV-associated morbidity by 10
      22% and HIV infections by 9-48% with increasing CD4 cell count thresholds for
      antiretroviral therapy initiation. Incremental programme costs were US$2.7
      million to $4.4 million higher in the intervention scenarios than at baseline,
      and costs increased with higher CD4 cell count thresholds for antiretroviral
      therapy initiation; antiretroviral therapy accounted for 48-87% of total costs.
      Incremental cost-effectiveness ratios per disability-adjusted life-year averted
      were $1340 at an antiretroviral therapy threshold of CD4 count lower than 200
      cells per MUL, $1090 at lower than 350 cells per MUL, $1150 at lower than 500
      cells per MUL, and $1360 at universal access to antiretroviral therapy.
      INTERPRETATION: Community-based HTC with enhanced linkage to care can result in
      increased HIV testing coverage and treatment uptake, decreasing the population
      burden of HIV-associated morbidity and mortality. The incremental cost
      effectiveness ratios are less than 20% of South Africa's gross domestic product
      per person, and are therefore classed as very cost effective. Home HTC can be a
      viable means to achieve UNAIDS' ambitious new targets for HIV treatment coverage.
      FUNDING: National Institutes of Health, Bill & Melinda Gates Foundation, Wellcome
      Trust.

PMID- 25844395
TI  - Enteric neuron imbalance and proximal dysmotility in ganglionated intestine of
      the Sox10Dom/+ Hirschsprung mouse model.
AB  - BACKGROUND & AIMS: In Hirschsprung disease (HSCR), neural crest-derived
      progenitors (NCPs) fail to completely colonize the intestine so that the enteric
      nervous system (ENS) is absent from distal bowel. Despite removal of the
      aganglionic region, many HSCR patients suffer from residual intestinal
      dysmotility. To test the hypothesis that inappropriate lineage segregation of
      NCPs in proximal ganglionated regions of the bowel could contribute to such
      postoperative disease, we investigated neural crest (NC)-derived lineages and
      motility in ganglionated, postnatal intestine of the Sox10Dom/+ HSCR mouse model.
      METHODS: Cre-mediated fate-mapping was applied to evaluate relative proportions
      of NC-derived cell types. Motility assays were performed to assess gastric
      emptying and small intestine motility while colonic inflammation was assessed by
      histopathology for Sox10Dom/+ mutants relative to wildtype controls. RESULTS:
      Sox10Dom/+ mice showed regional alterations in neuron and glia proportions as
      well as Calretinin+ and nNOS+ neuronal subtypes. In the colon, imbalance of
      enteric NC derivatives correlated with the extent of aganglionosis. All
      Sox10Dom/+ mice exhibited reduced small intestinal transit at 4-weeks of age, and
      at 6-weeks, Sox10Dom/+ males had increased gastric emptying rates. Sox10Dom/+
      mice surviving to 6-weeks of age had little or no colonic inflammation when
      compared to wildtype littermates, suggesting that these changes in GI motility
      are neurally mediated. CONCLUSIONS: The Sox10Dom mutation disrupts the balance of
      NC-derived lineages and affects GI motility in the proximal, ganglionated
      intestine of adult animals. This is the first report identifying alterations in
      enteric neuronal classes in Sox10Dom/+ mutants, which suggests a previously
      unrecognized role for Sox10 in neuronal subtype specification.

PMID- 25844396
TI  - Cutaneous Melanoma in Women.
AB  - The incidence of cutaneous melanoma (CM) continues to increase in the Caucasian
      population in the United States. In 2014, women only accounted for 42% of the
      76,100 new melanoma cases and only 33% of the 9,710 deaths associated with CM in
      the US.1 These trends are consistently observed in populations around the world.
      Indeed, gender disparity in melanoma outcome is so consistently observed that
      gender has been suggested as an important prognostic factor in melanoma, despite
      not being formerly incorporated in staging algorithms.2 The source of this gender
      disparity in melanoma remains unclear but likely represents both biological and
      behavioral etiologies. Herein, we review the current knowledge of how melanoma
      differs between men and women.

PMID- 25844397
TI  - Risk Factors for Venous Thromboembolism in Chronic Obstructive Pulmonary Disease.
AB  - BACKGROUND: COPD patients are at increased risk for venous thromboembolism (VTE).
      VTE however remains under-diagnosed in this population and the clinical profile
      of VTE in COPD is unclear. METHODS: Global initiative for chronic Obstructive
      Lung Disease (GOLD) stages II-IV participants in the COPD Genetic Epidemiology
      (COPDGene) study were divided into 2 groups: VTE+, those who reported a history
      of VTE by questionnaire, and VTE-, those who did not. We compared variables in
      these 2 groups with either t-test or chi-squared test for continuous and
      categorical variables, respectively. We performed a univariate logistic
      regression for VTE, and then a multivariate logistic regression using the
      significant predictors of interest in the univariate analysis to ascertain the
      determinants of VTE. RESULTS: The VTE+ group was older, more likely to be
      Caucasian, had a higher body mass index (BMI), smoking history, used oxygen, had
      a lower 6-minute walk distance, worse quality of life scores, and more dyspnea
      and respiratory exacerbations than the VTE- group. Lung function was not
      different between groups. A greater percentage of the VTE+ group described
      multiple medical comorbidities. On multivariate analysis, BMI, 6-minute walk
      distance, pneumothorax, peripheral vascular disease, and congestive heart failure
      significantly increased the odds for VTE by history. CONCLUSIONS: BMI, exercise
      capacity, and medical comorbidities were significantly associated with VTE in
      moderate to severe COPD. Clinicians should suspect VTE in patients who present
      with dyspnea and should consider possibilities other than infection as causes of
      COPD exacerbation.

PMID- 25844398
TI  - FMRP regulates neurogenesis in vivo in Xenopus laevis tadpoles.
AB  - Fragile X Syndrome (FXS) is the leading known monogenic form of autism and the
      most common form of inherited intellectual disability. FXS results from silencing
      the FMR1 gene during embryonic development, leading to loss of Fragile X Mental
      Retardation Protein (FMRP), an RNA-binding protein that regulates mRNA transport,
      stability, and translation. FXS is commonly thought of as a disease of synaptic
      dysfunction, however, FMRP expression is lost early in embryonic development,
      well before most synaptogenesis occurs. Recent studies suggest that loss of FMRP
      results in aberrant neurogenesis, but neurogenic defects have been variable. We
      investigated whether FMRP affects neurogenesis in Xenopus laevis tadpoles which
      express a homolog of FMR1. We used in vivo time-lapse imaging of neural
      progenitor cells and their neuronal progeny to evaluate the effect of acute loss
      or over-expression of FMRP on neurogenesis in the developing optic tectum. We
      complimented the time-lapse studies with SYTOX labeling to quantify apoptosis and
      CldU labeling to measure cell proliferation. Animals with increased or decreased
      levels of FMRP have significantly decreased neuronal proliferation and survival.
      They also have increased neuronal differentiation, but deficient dendritic arbor
      elaboration. The presence and severity of these defects was highly sensitive to
      FMRP levels. These data demonstrate that FMRP plays an important role in
      neurogenesis and suggest that endogenous FMRP levels are carefully regulated.
      These studies show promise in using Xenopus as an experimental system to study
      fundamental deficits in brain development with loss of FMRP and give new insight
      into the pathophysiology of FXS.

PMID- 25844399
TI  - Predicted vs. Actual Resting Energy Expenditure and Activity Coefficients: Post
      Gastric Bypass, Lean and Obese Women.
AB  - Total Energy Expenditure (TEE) and energy requirements are commonly estimated
      from equations predicting Resting Energy Expenditure (REE) multiplied by a
      Physical Activity (PA) coefficient that accounts for both PA energy expenditure
      and the thermogenic effect of food. PA coefficients based on PA self-reports are
      a potential source of error that has not been evaluated. Therefore, in this study
      we compared: 1) the Harris-Benedict (HB), Mifflin-St. Jeor (MSJ), and the Food
      and Agriculture Organization/World Health Organization/United Nations University
      (FAO/WHO/UNU) REE equations with REE measured (REE-m) with indirect calorimetry;
      2) PA coefficients determined with PA self-reports vs. objectively assessed PA;
      and 3) TEE estimates in post-Gastric Bypass (GB = 13), lean (LE = 7), and obese
      (OB = 12) women. REE was measured in the morning after an overnight fast with
      participants resting supine for 30 min. Self-reported PA was evaluated with a
      questionnaire and objectively measured with accelerometers worn for 5-7 days.
      Nutritional intake was evaluated with a food frequency questionnaire.
      Anthropometry included DEXA, and abdominal CT scans. Eligible GB had surgery >=
      12 months before the study, and had >= 10 kg of body weight loss. All
      participants were 18-45 years of age, able to engage in ambulatory activities,
      and not taking part in exercise training programs. One-way ANOVA was used to
      detect differences in REE and TEE. Accuracy of REE prediction equations were
      determined by cases within 10% of REE-m, and agreement analyses. REE predictions
      were not different than REE-m, but agreements were better with HB and MSJ,
      particularly in the GB and LE groups. Discrepancies in the PA coefficients
      determined with self-report vs. objectively assessed PA resulted in TEE
      overestimates (approximately 200-300 Kcal/day) using HB and MSJ equations.
      FAO/WHO/UNU overestimated TEE in all groups regardless of the PA assessment
      method (approximately 300-900 kcal/day). These results suggest that: 1) HB and
      MSJ equations are good predictors of REE among GB and LE, but not among OB women,
      2) PA coefficients used to estimate TEE must be determined with objective PA
      assessment, and 3) TEE estimates using PA coefficients with the FAO/WHO/UNU
      equation must be used with caution.

PMID- 25844400
TI  - IPEX Syndrome, FOXP3 and Cancer.
AB  - In this review, we introduce the IPEX syndrome and its relationship with germline
      mutations of the FOXP3 gene. We then describe the multiple functional roles of
      FOXP3 in regulatory T cells and epithelial cells as well as in IPEX syndrome and
      tumor progression. Potential mechanisms of FOXP3 inactivation and transcriptional
      regulation are discussed with recent advances. Finally, we point out current
      issues and a potential FOXP3-mediated therapeutic strategy as well as the
      reactivation of FOXP3 in patients with IPEX syndrome and cancer.

PMID- 25844402
TI  - Optimizing the Most Specific Concept Method for Efficient Instance Checking.
AB  - Instance checking is considered a central tool for data retrieval from
      description logic (DL) ontologies. In this paper, we propose a revised most
      specific concept (MSC) method for DL SHI, which converts instance checking into
      subsumption problems. This revised method can generate small concepts that are
      specific-enough to answer a given query, and allow reasoning to explore only a
      subset of the ABox data to achieve efficiency. Experiments show effectiveness of
      our proposed method in terms of concept size reduction and the improvement in
      reasoning efficiency.

PMID- 25844401
TI  - SimConcept: A Hybrid Approach for Simplifying Composite Named Entities in
      Biomedicine.
AB  - Many text-mining studies have focused on the issue of named entity recognition
      and normalization, especially in the field of biomedical natural language
      processing. However, entity recognition is a complicated and difficult task in
      biomedical text. One particular challenge is to identify and resolve composite
      named entities, where a single span refers to more than one concept(e.g.,
      BRCA1/2). Most bioconcept recognition and normalization studies have either
      ignored this issue, used simple ad-hoc rules, or only handled coordination
      ellipsis, which is only one of the many types of composite mentions studied in
      this work. No systematic methods for simplifying composite mentions have been
      previously reported, making a robust approach greatly needed. To this end, we
      propose a hybrid approach by integrating a machine learning model with a pattern
      identification strategy to identify the antecedent and conjuncts regions of a
      concept mention, and then reassemble the composite mention using those identified
      regions. Our method, which we have named SimConcept, is the first method to
      systematically handle most types of composite mentions. Our method achieves high
      performance in identifying and resolving composite mentions for three fundamental
      biological entities: genes (89.29% in F-measure), diseases (85.52% in F-measure)
      and chemicals (84.04% in F-measure). Furthermore, our results show that, using
      our SimConcept method can subsequently help improve the performance of gene and
      disease concept recognition and normalization.

PMID- 25844403
TI  - Multi-Dimensional Scaling and MODELLER-Based Evolutionary Algorithms for Protein
      Model Refinement.
AB  - Protein structure prediction, i.e., computationally predicting the three
      dimensional structure of a protein from its primary sequence, is one of the most
      important and challenging problems in bioinformatics. Model refinement is a key
      step in the prediction process, where improved structures are constructed based
      on a pool of initially generated models. Since the refinement category was added
      to the biennial Critical Assessment of Structure Prediction (CASP) in 2008, CASP
      results show that it is a challenge for existing model refinement methods to
      improve model quality consistently. This paper presents three evolutionary
      algorithms for protein model refinement, in which multidimensional scaling(MDS),
      the MODELLER software, and a hybrid of both are used as crossover operators,
      respectively. The MDS-based method takes a purely geometrical approach and
      generates a child model by combining the contact maps of multiple parents. The
      MODELLER-based method takes a statistical and energy minimization approach, and
      uses the remodeling module in MODELLER program to generate new models from
      multiple parents. The hybrid method first generates models using the MDS-based
      method and then run them through the MODELLER-based method, aiming at combining
      the strength of both. Promising results have been obtained in experiments using
      CASP datasets. The MDS-based method improved the best of a pool of predicted
      models in terms of the global distance test score (GDT-TS) in 9 out of 16test
      targets.

PMID- 25844404
TI  - INSIGHTS INTO THE MECHANICS OF CYTOKINETIC RING ASSEMBLY USING 3D MODELING.
AB  - During fission yeast cytokinesis, actin filaments nucleated by cortical formin
      Cdc12 are captured by myosin motors bound to a band of cortical nodes. The myosin
      motors exert forces that pull nodes together into a contractile ring. Cross
      linking interactions help align actin filaments and nodes into a single bundle.
      Mutations in the myosin motor domain and changes in the concentration of cross
      linkers alpha-actinin and fimbrin alter the morphology of the condensing network,
      leading to clumps, rings or extended meshworks. How the contractile tension
      developing during ring formation depends on the interplay between network
      morphology, myosin motor activity, cross-linking and actin filament turnover
      remains to be elucidated. We addressed this question using a 3D computational
      model in which semiflexible actin filaments (represented as beads connected by
      springs) grow from formins, can be captured by myosin in neighboring nodes, and
      get cross-linked with one another through an attractive interaction. We identify
      regimes of tension generation between connected nodes under a wide set of
      conditions regarding myosin dynamics and strength of cross-linking between actin
      filaments. We find conditions that maximize circumferential tension, correlate
      them with network morphology and propose experiments to test these predictions.
      This work addresses "Morphogenesis of soft and living matter" using computational
      modeling to simulate cytokinetic ring assembly from the key molecular mechanisms
      of viscoelastic cross-linked actin networks that include active molecular motors.

PMID- 25844405
TI  - [From the editor - epidemiology of mental diseases].

PMID- 25844406
TI  - ["Epidemiology of mental disorders and access to mental health care. EZOP -
      Poland" - research methodology].
AB  - AIM: Since the second half of the twentieth century, with the development of
      structured diagnostic tools, population based studies on epidemiology of mental
      disorders are carried out. A special role is played by World Mental Health Survey
      Initiative which brings together a group of countries from different continents
      in order to carry out research projects according to standard methodology using
      the Composite International Diagnostic Interview. Polish EZOP study, which was
      conducted in accordance with the guidelines of WMH joined that group. The project
      was implemented under the Norwegian Financial Mechanism and the Financial
      Mechanism of the European Economic Area. Its aim was to estimate the prevalence
      of mental disorders in the Polish population of adults, assess the distance to
      mental disorders and to obtain knowledge about the perception of psychiatric
      disorders and treatment. METHODS: The research tool was the Polish version of
      CIDI-WHO ver.3.0., which was developed for the project. The study was performed
      in accordance with the guidelines of WMH (cognitive interviews, interviewers
      training, standardization of field procedures) using electronic version of CIDI
      questionnaire (CAPI) within the 2-stages procedure in randomly selected
      representative sample of the Polish population aged 18-64. The quality of the
      study was systematically controlled and reported by MB SMG/KRC, and completed
      data (10,081 interviews) were sent to the Department-Centre of Monitoring and
      Analyses of Population Health NIPH-NIH. After the initial analysis data were sent
      to the analytical center of WMH, which applied additional cleaning tools and
      added new variables representing psychiatric diagnoses in DSM-IV and ICD-10.

PMID- 25844407
TI  - [The prevalence of common mental disorders in the population of adult Poles by
      sex and age structure - an EZOP Poland study].
AB  - AIM: The article presents lifetime (LT) prevalence of common mental disorders
      (CMD) in accordance with the DSMIV classification, based on assessment of
      representative population sample of 10,081 Poles aged 18-64. METHODS: Computer
      based WHO CIDI3.0 was adapted for the Polish population according to WMH
      protocol. The survey was performed by certified and supervised interviewers.
      RESULTS: Out of the 18 CMDs analyzed the most common was alcohol abuse,
      significantly more often in males (18.6%) than in women (3.3%), (p<0.01). The
      second most common disorder was panic, also more frequent in women (8.5%) than in
      men (3.9%), (p<0.01). Similarly, depression occurred in women (4.0%) two times
      more often than in males (1.9%), (p<0.01). GAD, agoraphobia, panic, specific
      phobia (p<0.01), and dysthymia (p<0.05) were also more prevalent in women. On the
      other hand, alcohol abuse, alcohol and drug dependence (p<0.01), and hypomania
      (p<0.05) were more common in males. For most analyzed disorders significantly
      higher prevalence was found in the older age groups. Social phobia, specific
      phobias, and drug abuse occurred most often in men from the youngest group. No
      significant differences related to age were found for the prevalence of hypomania
      both in men and women. CONCLUSIONS: Indices of prevalence obtained in the EZOP
      Poland study differ from the indices of prevalence of mental disorders described
      earlier in other countries. Lower values were found in Poland for affective
      disorders and some anxiety disorders. Only alcohol abuse was diagnosed more often
      than in other studies using similar methods except Ukraine, where this disorder
      was diagnosed with similar frequency.

PMID- 25844408
TI  - [Effectiveness of intensive group psychotherapy in treatment of neurotic and
      personality disorders].
AB  - AIM: The aim of this study was to analyze the effectiveness of intensive (150 -
      210 sessions), short-term (10 - 14 weeks) group psychotherapy in the treatment of
      neurotic disorders, and selected personality disorders. METHODS: The study
      involved 145 patients treated in day hospital due to neurotic disorders and
      selected personality disorders. The measurements were performed twice - at the
      beginning and at the end of hospitalization. The effectiveness of psychotherapy
      in the reduction of symptoms of neurotic disorders was measured with symptom
      checklist "0". The change in the severity of personality traits characteristic
      for neurotic disorders was examined using Neurotic Personality Questionnaire KON
      2006. RESULTS: A significant reduction in symptoms of neurotic disorders was
      found in 84% of patients (85,7% women and 80,8% men). 70,3% of the examined
      patients obtained in the measurement at the end of treatment results indicating
      the level of severity of neurotic disorders symptoms below the cutoff point
      separating population of healthy individuals from patients. A significant
      reduction in the severity of personality traits characteristically occurring in
      patients suffering from neurotic disorders was found in 76% of patients (74.5%
      women and 78.7% men). 42.8% of the examined patients obtained in the measurement
      at the end of the treatment the value of neurotic personality traits index (X
      KON) typical for healthy population. CONCLUSIONS: Intensive, short-term group
      psychotherapy with elements of individual therapy is an effective treatment for
      neurotic disorders. The majority of treated persons obtains a significant
      symptomatic improvement and a reduction in the severity of neurotic personality
      traits.

PMID- 25844409
TI  - [Psychotherapy for pregnant women with psychiatric disorders].
AB  - Pregnancy is a major life change for many women. The related biological changes,
      especially complications in its course and in the course of delivery, carry a
      risk of developing a variety of psychological problems and mental disorders.
      However, their treatment is challenging due to the teratogenic effects of most
      psychoactive drugs and specific requirements for entering different
      psychotherapeutic programs. Mental disorders during pregnancy are undoubtedly an
      important issue for both gynecology and psychiatry. There is still a discussion
      considering the question whether psychotherapy during pregnancy is safe, although
      no scientifically valid data contradicting the safety of psychotherapy during
      pregnancy has been published so far. Together with psychotherapy - as a treatment
      of choice - clinicians approve some other relatively safe treatment methods for
      psychiatric disorders in pregnant women. Light therapy, limited pharmacotherapy,
      ECT are included. The goal of this paper is to review current opinions of
      clinicians and researches concerning possibilities, indications and outcome of
      psychological treatments as a way to help pregnant women who suffer from
      different psychiatric conditions, and also because this subject is not yet
      present in Polish psychiatric journals. 

PMID- 25844410
TI  - [Attentional bias training in reducing symptoms of anxiety].
AB  - Anxiety is related to attentional bias, i.e. a tendency to pay attention to
      threatening stimuli. This occurs both in individuals suffering from anxiety
      disorders, and in healthy individuals with elevated levels of trait anxiety. This
      article is an analysis of a research paradigm, used to modify attentional bias
      (CBM-A Cognitive Bias Modification - Attention). A growing number of studies
      indicate that with the help of computer methods such as a modified version of the
      dot-probe task we can train individuals to direct attention away from threatening
      stimuli, which in turn reduces symptoms of anxiety. This effect was observed in
      adults, adolescents and children suffering from social phobia, generalised
      anxiety disorder and subclinical symptoms of obsessive-compulsive disorder.
      Effectiveness of this method constitutes the evidence for attentional bias being
      among the causes of anxiety disorders. The article also analyses the still not
      completely clear mechanisms of CBM-A and limitations of this method. 

PMID- 25844411
TI  - [The place of quetiapine extended release in the treatment of mental disorders].
AB  - This article presents a summary of available data on the use of quetiapine
      extended release (QUE-XR). QUE-XR is an example of an atypical antipsychotic drug
      that can be used in a single dose, thereby simplifying the treatment regimen.
      From the therapeutic standpoint, this issue is of paramount importance, since
      approximately 50% of patients have adherence issues. Therefore, availability of
      the drug which is comfortable in administration can significantly improve
      treatment outcomes. Due to its antipsychotic, antidepressive, mood stabilizing
      and anxiolytic efficacy, QUE-XR seems to be a promising drug with potentially
      broad spectrum of indications (in patients with schizophrenia, bipolar disorder,
      major depression and some anxiety disorders - both in the acute phase of
      treatment, and the maintenance treatment). Notably, QUE-XR seems to ameliorate
      sleep disturbances, and it may also improve patients' quality of life (as
      suggested by some studies). Due to the simple dosing regimen of QUE-XR,
      conducting therapy with this drug may contribute to the improvement of
      compliance. Yet, the primary clinical criterion for selection of the type of
      formulation of quetiapine should be the individual preferences of the patient,
      and the knowledge and experience of the treating physician. 

PMID- 25844412
TI  - [Misuse and abuse of quetiapine].
AB  - Quetiapine is an atypical antipsychotic agent, frequently used in psychiatry,
      often for symptomatic treatment against a number of mental disorders differing
      from the registration indications. One of the use is to soothe the clinical
      conditions caused by the use of various psychoactive substances. The paper
      presents and discusses the reports of quetiapine misuse, abuse, and even mental
      addiction, as well as symptoms similar to the so-called discontinuation syndrome,
      often mixed with withdrawal syndrome occurring in the course of addiction. Most
      reports concern males, and especially those with a history of other psychoactive
      substance abuse, and personality disorders, often in conflict with the law.
      Therefore, clinicians should be cautious when prescribing quetiapine to such
      patients. The article discusses potential mechanisms responsible for quetiapine
      abuse. This is probably related to its sedative and anxiolytic activity which
      results in the frequent use with stimulants. Also, high affinity for the H1
      receptor, as antihistamines agents causes rewarding action. 

PMID- 25844413
TI  - [The Polish adaptation of the public speaking anxiety questionnaire].
AB  - OBJECTIVES: The aim of the study was the Polish adaptation of the shortened
      Public Speaking Anxiety Questionnaire GFER by Spitznagel and co-workers. METHODS:
      GFER is a self-assessment method which consists of 16 statements and is designed
      to assess emotions, physiological reactions, and thoughts that appear in a
      situation of public speaking. GFER was used to examine 320 students from Lodz's
      universities. The State/Trait Anxiety Inventory - STAI by Spielberger, The
      Hospital Anxiety and Depression Scale by Zigmunt and Snaith and TCI by Cloninger
      were also used. RESULTS: The Polish version of GFER is a reliable and valid tool.
      The factor structure is similar to the original structure. As a result of the
      conducted analyses, there was obtained the 9-item version of the tool, which has
      a 2-factor structure - factor I: emotional and physiological reactions, factor
      II: worrying. The results obtained with GFER present a statistically significant
      correlation with other measures of anxiety and with the dimension of temperament:
      harm avoidance. CONCLUSIONS: The obtained results indicate that GFER may be used
      in both scientific research and therapeutic practice.

PMID- 25844414
TI  - [Perceived Autonomy in Old Age scale: Factor structure and psychometric
      properties of the Polish adaptation].
AB  - AIM: Sense of autonomy - the possibility to choose and decide - is one of the
      markers of positive and active aging. The goal of this study was to examine the
      Polish adaptation of the Perceived Autonomy in Old Age (PAA) scale and to
      determine its internal structure and psychometric properties: reliability, as
      well as construct and discriminant validity. METHODS: 277 seniors (female=187;
      male=90), without cognitive function disorders aged 60 to 100 (M=77.4; SD=9.2)
      took part in the study. Apart from the PAA, the ADL and IADL scales (self
      reliance assessment) were used, as well as the Emotional State Questionnaire (a
      measure for positive and negative emotions) and the WHOQoL-Brief (a measure for
      health-related quality of life). RESULTS: As a result of an exploratory and
      confirmation factor analysis a one-factor tool with five items was built.
      Reliability coefficients of the scale measured with the internal consistency
      method and test-retest were >= 0.80. Positive correlations were found with
      indicators in the ADL, IADL, as well as in the somatic and psychological domain
      of life quality, and positive emotions. Negative correlations were found for
      negative emotions. CONCLUSIONS: The obtained results indicated very high
      reliability and accuracy for the Polish adaptation of the SPA. The tool can be
      used as a predictor and/or indicator of successful aging and life quality of
      seniors.

PMID- 25844415
TI  - [Validation of ORTO-15 Questionnaire in the group of urban youth aged 15-21].
AB  - AIM: The aim of the study was the validation and adaptation of the ORTO-15
      Questionnaire in the group of the Polish schoolgirls and schoolboys. METHODS: The
      study included 399 participants (15-21 years old), all of them high school
      students in the city of Sosnowiec. The ORTO-15 is a tool created in Italy by L.M.
      Donini, comprising of 15 items describing intensification of orthorexia risk
      (population diagnosis). The validation procedure incorporated three basic methods
      to be applied in the reliability analysis - the comparison of double tests with
      the same method, the statistical properties analysis of test items as well as
      analysis of the relation of test items with the general test result. Moreover,
      the compliance of the ORTO-15 Questionnaire results with other questionnaire
      focused on eating habits (EAT-26) was studied. RESULTS: The reliability analysis
      of the ORTO-15 Questionnaire based on repeatability of the responses presents a
      very good (kappa: 0.81 - 1.00 for 5 items) and a good repeatability (kappa: 0.61 
      0.80 for 10 items). The reliability analysis based on the value of the
      Cronbach's alpha reached a satisfactory level (0.7 - 0.9). A full agreement of in
      the occurrence of orthorexia risk and the risk of eating disorders concerned
      47.2% (Kappa = 0.04; 95% CI: 0.004 - 0.09) for the Ortho-40 and 88.2% (Kappa =
      0.32; 95% CI: 0.17 - 0.47) for the Ortho-35. CONCLUSIONS: The ORTO-15
      questionnaire is a reliable tool to identify the risk of ON in population studies
      in the group of urban youth aged 15 - 21.

PMID- 25844416
TI  - [Psychometric properties of the Polish version of the brief version of Kutcher
      Adolescent Depression Scale - assessment of depression among students].
AB  - AIM: Depressive disorders, which remain one of the most common and recurrent mood
      disorders worldwide, presently affect up to 15% of the population under age 25.
      Adolescent depression is related to a number of adverse phenomena such as
      scholastic/academic failure, juvenile delinquency, illicit substance abuse or
      suicide. Studies show that students are at a high risk of developing this
      disorder but depression in this population is often misdiagnosed and
      undertreated. Consequently, it is important to develop reliable diagnostic tools
      to evaluate symptoms of depression in students. Kutcher Adolescent Depression
      Scale (brief version) is a commonly used screening test used to identify young
      people at risk for depression, which consists of six items related to its main
      symptoms. The aim of the study was to adapt and test reliability and content
      validity of the Polish version of six - item Kutcher's KADS based on analysis of
      students using confirmatory factor analysis. MATERIAL AND METHODS: A total of
      1,589 student aged 18-24 anonymously answered a questionnaire on the risk of
      depression (KADS) and a demographics survey. RESULTS: Confirmatory factor
      analysis showed the good fit of model to empirical data: SB chi2 (15) = 968.688,
      p < .001, RMSEA = .053, CFI = .958, SRMR = .029. Factor loading ranged from .40
      to .80. CONCLUSIONS: Validation of Polish version of KADS in a group of students
      aged 18-24 years has shown its high reliability and content validity. Further
      studies should be focused on the assessment of the questionnaire criterion
      validity.

PMID- 25844417
TI  - [The study of the Polish version of the Questionnaire for the Assessment of
      Disgust Sensitivity (QADS)].
AB  - AIM: Disgust is one of the principal emotions, typically triggered by a variety
      of biological and social stimuli. Several questionnaire tools have been used to
      assess disgust. The aim of the study was to assess psychometric properties of the
      Polish version of the Questionnaire for the Assessment of Disgust Sensitivity
      (QADS), adapted from the tool prepared by the German researchers. METHODS: Eight
      hundred twenty subjects (631, 77% females and 189, 23% males) aged 18-69 (mean -
      28 years) participated in the study. There are 3 subscale in the questionnaire:
      Core Disgust, Animal Reminder and Contamination. The tool consists of 37 items,
      the intensity of feeling of disgust is assessed based on 5-point Likert scale.
      RESULTS: Confirmatory factor analysis confirmed the adequacy of grouping of items
      in the three subscales: Core Disgust, Animal-Reminder, and Contamination
      Interpersonal. In our sample, females had higher levels of disgust than males.
      Several other psychometric variables - high degree of correlations between the
      subscales, and high reliability -were in agreement with parameters of the
      original version. The Polish version compared favourably with the original, with
      Cronbach's alpha of 0.94 for the whole questionnaire and 0.85 - 0.90 for the
      subscales. CONCLUSIONS: The psychometric properties of the Polish version of QADS
      are sufficient to recommend this tool for diagnostic and research use.

PMID- 25844418
TI  - [Diagnosis of Posttraumatic Stress Disorder (PTSD) by the Structured Clinical
      Interview SCID-I].
AB  - OBJECTIVES: Valid and reliable diagnosis of posttraumatic stress disorder is
      important for clinical practice, scientific research and forensic settings. The
      aim of the study was to assess the psychometric properties of the Polish version
      of SCID-I F Module for the diagnosis of PTSD. METHODS: Five hundred twenty six
      motor vehicle accident survivors participated in the study. Clinical diagnosis
      was based on SCID-I-PTSD interview. Participants filled out a set of self-report
      inventories concerning PTSD symptoms (PDS), depression (BDI-II), anxiety (STAI)
      and posttraumatic cognitions (PTCI). RESULTS: The interview assessment showed
      high reliability and both convergent and discriminative validity. SCID-I-PTSD
      interview proved to be more specific than PDS inventory. Interview items show
      good psychometric properties (except an item C3) and no differential item
      functioning for sex. Latent structure analysis of PTSD symptoms were
      nonconclusive. CONCLUSIONS: A part of Module F of the SCID-I, a structured
      clinical interview for the assessment of posttraumatic stress disorder is a valid
      and reliable psychometric tool useful for the diagnosis of PTSD.

PMID- 25844420
TI  - [The diagnostic usability of selected narrativity indices in stories about close
      relationships in the assessment of personality organization].
AB  - AIM: The aim of this study was to test the usability of selected narrativity
      indices identified from autobiographical accounts of important relationships in
      an assessment of neurotic (NPO) and borderline personality organization (BPO).
      METHODS: Narrativity indices, both particular and generalized, were used to
      predict personality organization levels. Indices were derived from two separate
      layers of analysis: 1) lexical indices were counted with computer assistance; 2)
      evocative/reception indices dealing with coherence of the story were assessed
      using the competent judges method. RESULTS: It was found that the lexical
      narrativity index-the active "I"-was a good predictor of both BPO and NPO, while
      the human factor was a good predictor of BPO when low. Moreover, a generalized
      index was used to describe how stories are saturated with the narrativity indices
      of intentionality, concreteness, and active "I", but simultaneously deprived of
      human factor, and was found to be the best predictor of BPO. Furthermore, where
      the coherence of the story and of its subdimension (integration) rise, the
      probability of BPO diagnosis decreases. CONCLUSIONS: This research provides
      support for the thesis that surface narrativity indices may predict deeper
      personality structure. Its results are justified in the light of Kernberg's
      theory, and have the potential to become a useful tool in clinical practice as a
      supplementary source of information in diagnostic and psychotherapeutic
      processes.

PMID- 25844421
TI  - Assessing humanity's global impact.

PMID- 25844419
TI  - [The Montreal Cognitive Assessment 7.2--Polish adaptation and research on
      equivalency].
AB  - AIM: The Montreal Cognitive Assessment is a screening test for diagnosis of Mild
      Cognitive Impairment- MCI. Only one version of the method was available in Poland
      so far. In order to assess progression of cognitive impairment, or to diagnose
      effectiveness of therapy, two equivalent version of method are needed. English
      additional version 7.2. was translated and culturally adapted to sustain
      reliability of the assessment. Then equivalency of both Polish versions was
      investigated. This paper examines whether both Polish versions of MoCA are
      equivalent, and describes the process of its cultural adaptation. METHODS: 66
      psychiatric patients (37 men, 29 women) with different levels of cognitive
      impairment were examined using both Polish versions of MoCA. Both versions were
      administered randomly to patients with no time interval in between. RESULTS: No
      significant differences (p=0,601) for total MoCA scores were found between first
      version of Polish MoCA, and alternate version. Equivalency measured by
      correlation coefficient Spearman's rho correlation coefficient (rho=0,926) proved
      to be high. CONCLUSIONS: Both Polish versions of MoCA are equivalent, and can be
      useful in repeated measurement of progress in cognitive impairment or in testing
      of the effectiveness of treatment.

PMID- 25844422
TI  - Q&A: Stephen M. Kosslyn.

PMID- 25844423
TI  - Home healthcare: expertise needed.

PMID- 25844424
TI  - [A loud reflection...].

PMID- 25844425
TI  - [Farewell].

PMID- 25844426
TI  - The introduction of a lightweight mini vaporizer and malignant hyperthermia:
      author reply.

PMID- 25844427
TI  - [Jaime Celestino da Costa].

PMID- 25844428
TI  - Occupational health: additional support for the aging anesthesiologist: author
      reply.

PMID- 25844429
TI  - Associations of breaks in sedentary time with abdominal obesity in Portuguese
      older adults.
AB  - In older adults, sedentary time is positively associated with obesity. The manner
      in which it is accumulated, i.e., the number of breaks in sedentary time, might
      be also important. We examined the cross-sectional associations of breaks in
      sedentary time with abdominal obesity in 301 older adults (111 men and 190 women)
      aged 75.0 +/- 6.8 years. Sedentary time (counts min(-1) < 100) and physical
      activity were objectively measured by accelerometry, worn during waking hours for
      at least three consecutive days. A break was defined as an interruption (>= 100
      counts min(-1) < 2020) in sedentary time while performing light intensity
      physical activities. Sedentary time was expressed as the number of daily breaks
      in sedentary time or hourly breaks in sedentary time. Abdominal obesity was
      defined by waist circumference (men >102 cm; women >88 cm). Using binary logistic
      regression analyses, the odds for abdominal obesity decreased 7 % for each
      additional hourly break in sedentary time in women (OR = 0.93, 95 % CI: 0.87
      1.00), but not men, independently of total sedentary time and moderate-to
      vigorous physical activity. The odds for abdominal obesity were 3.21 times higher
      (p = 0.039) for women in quartile 1 (<225 breaks day(-1)) of daily breaks in
      sedentary time compared to those in quartile 4 (>353 breaks day(-1)) of daily
      breaks in sedentary time.These findings indicate that older women who interrupt
      their sedentary time more frequently are less likely to present abdominal
      obesity. Public health recommendations regarding breaking-up sedentary time
      complementary to those for physical activity are likely to be relevant.

PMID- 25844430
TI  - Plant salt tolerance: adaptations in halophytes.
AB  - BACKGROUND: Most of the water on Earth is seawater, each kilogram of which
      contains about 35 g of salts, and yet most plants cannot grow in this solution;
      less than 0.2% of species can develop and reproduce with repeated exposure to
      seawater. These 'extremophiles' are called halophytes. SCOPE: Improved knowledge
      of halophytes is of importance to understanding our natural world and to enable
      the use of some of these fascinating plants in land re-vegetation, as forages for
      livestock, and to develop salt-tolerant crops. In this Preface to a Special Issue
      on halophytes and saline adaptations, the evolution of salt tolerance in
      halophytes, their life-history traits and progress in understanding the
      molecular, biochemical and physiological mechanisms contributing to salt
      tolerance are summarized. In particular, cellular processes that underpin the
      ability of halophytes to tolerate high tissue concentrations of Na+ and Cl-,
      including regulation of membrane transport, their ability to synthesize
      compatible solutes and to deal with reactive oxygen species, are highlighted.
      Interacting stress factors in addition to salinity, such as heavy metals and
      flooding, are also topics gaining increased attention in the search to understand
      the biology of halophytes. CONCLUSIONS: Halophytes will play increasingly
      important roles as models for understanding plant salt tolerance, as genetic
      resources contributing towards the goal of improvement of salt tolerance in some
      crops, for re-vegetation of saline lands, and as 'niche crops' in their own right
      for landscapes with saline soils.

PMID- 25844431
TI  - In the midst of a large measles outbreak, EDs take steps to bolster screening
      procedures, prevent potential transmissions.
AB  - A large, multi-state outbreak of measles is prompting EDs around the country to
      bolster their screening procedures and provide education to staff, most of whom
      have never seen a measles case. Dozens of people in more than 17 states have been
      confirmed to have the disease, with most of these cases associated with an
      outbreak that began at an amusement park in southern California. Measles is
      extremely contagious, infecting nine out of 10 people exposed to the virus if
      they are susceptible to the disease. In cases in which a contagious disease is
      suspected, experts advise emergency providers to protect themselves before
      proceeding to the traditional vital signs. It's a concept referred to as "vital
      sign zero." Once a measles case is confirmed, experts say emergency staff should
      isolate the patient with protection such as an N-95 mask, and inform both the
      hospital's infection control department and public health authorities.

PMID- 25844432
TI  - The role of emergency medicine in curbing, preventing measles outbreaks.

PMID- 25844433
TI  - New type of center focuses on caring for the most critically ill patients,
      decompressing ED that serves patients at the upper end of the acuity spectrum.
AB  - The University of Michigan Health System (UMHS) in Ann Arbor has opened a new
      unit within its ED to focus on caring for the most critically ill patients Who
      present to the ED. Dubbed the Massey Emergency Critical Care Center, or EC3, the
      model is the first of its kind in the country, with its own ICU and a lower nurse
      patient ratio than the main ED to facilitate closer monitoring. Developers
      hope.the new unit will decompress the ED, shorten wait times, and potentially
      reduce the demand for ICU care on the upper floors. The adult ED at UMHS receives
      patients on the higher end of the acuity spectrum, with high-acuity patients
      making up 90% of the patient volume. Staffing of the EC3 includes emergency
      nurses and physicians who have had extra training in critical care. The EC3 will
      serve as a new research center for emergency critical care patients, and a
      training ground for physicians and nurses looking to enhance their skills in
      critical care.

PMID- 25844434
TI  - Study: bacterium associated with rare "forgotten" disease also responsible for
      more sore throats than Group A strep in young adults.
AB  - New findings show that Fusobacterium necrophorum, the bacterium responsible for
      most cases of Lemierre's disease, a relatively rare condition that is sometimes
      called "the forgotten disease," is also the culprit for more sore throats than
      Group A strep bacterium among college-aged patients. However, as there is no
      point-of-care test for F. necrophorum, providers need to rely on physical
      examination when determining whether a sore throat is due to the bacterial
      infection. In an analysis of 312 college students, investigators detected F.
      necrophorum in more than 20% of patients with symptoms of sore throat. Group A
      strep was only detected in 10% of the cases, and Group C or G strep was detected
      in 9% of the cases. Researchers note that the F. necrophorum bacterium is
      associated with both Lemierre's disease and most cases involving a peritonsillar
      abscess, a deep infection of the head or neck that occurs most commonly in young
      adults. Infections caused by F. necrophorum can be effectively treated with
      penicillin or a cephalosporin, but do not typically respond to azithromycin.

PMID- 25844435
TI  - [Macular surgery in a new point of view].
AB  - PURPOSE: To reveal the differences in anatomical and functional results following
      standard 20-gauge vitrectomy and modern transconjunctival sutureless vitrectomy
      in macular surface pathology. MATERIALS AND METHODS: Retrospective,
      interventional, comparative evaluation of macular pathology cases operated by
      standard 20-gauge vitrectomy and transconjunctival 23 G sutureless vitrectomy. In
      evaluation were included a comparable number of epiretinal membranes (both
      idiopathic and secondary) and stage 3 and 4 macular holes. A postoperative
      anatomical and functional analysis was performed and also the incidence of pre
      and postoperative complications was noted. RESULTS: Transconjunctival sutureless
      vitrectomy was associated with a shorter operating time and quicker anatomical
      and functional results. If in epiretinal membranes there was no significant
      difference in final results, in macular holes anatomical and functional results
      were better with sutureless vitrectomy. CONCLUSIONS: These results confirm the
      efficacy and safety of both surgical procedures in macular surface pathology.
      Better anatomical and functional results in macular holes and quicker functional
      rehabilitation in all cases promote sutureless vitrectomy as new standard
      procedure in these cases.

PMID- 25844436
TI  - [Thermophilic prokaryotes from deep subterranean habitats].
AB  - The deep continental biosphere consists of geologically isolated ecosystems
      differing in their physicochemical, geological, and trophic parameters. Most of
      the deep ecosystems exist at elevated temperatures (50-120 degrees C), which
      favor the development of thermophilic microorganisms. In many cases, indigenous
      nature of subsurface microorganisms is questionable due to problems of collecting
      representative and non-contaminated samples. In spite of the numerous studies on
      the deep biosphere microbial communities, the number of cultivated thermophiles
      isolated from subsurface environments not associated with petroleum deposits does
      not exceed 30 species. More than half of the thermophilic species isolated from
      deep subsurface belong to the Firmicutes. Majority of the underground
      thermophiles are subsurface strict or facultative anaerobes, with capacity for
      sulfate and iron reduction are notably widespread. Most thermophilic subsurface
      microorganisms are organotrophs, although chemolithoautotrophic thermophiles also
      have been reported. This review deals with the phylogenetic diversity and
      physiological properties of the cultivated thermophilic prokaryotes isolated from
      various deep subterranean habitats.

PMID- 25844437
TI  - [Trehalose: chemical structure, biological functions, and practical application].
AB  - Up-to-date information concerning the chemical structure and properties of
      trehalose, its natural occurrence and biological functions in plants, fungi, and
      prokaryotes, as well as its practical application, mainly in medicine and
      biotechnology, are reviewed. A special section deals with the role of trehalose
      and other protective polyols in stress processes in fungi.

PMID- 25844438
TI  - [Changes in the phase variant spectra in the populations of lactic acid bacteria
      under antibiotic treatment].
AB  - Effect of the antibiotics kanamycin and ampicillin on growth and phase variation
      of the populations of four strains of lactic acid bacteria (Lactobacillus sp.
      M67AT, L. casei MB, Enterococcus faecium M, and E. faecium M3185) was studied.
      The presence of antibiotics in the medium resulted in a dose-dependent decrease
      in viable cell numbers and in partial or complete substitution of the dominant S
      variant with the minor Sm and Sb variants. The variants differed in colony
      morphology, as well as in some physiological, biochemical, biotechnological, and
      probiotic characteristics. The Sm type variants of all strains exhibited the
      highest resistance to antibiotics. High production of exopolysaccharides was
      found in Sb variants of lactobacilli and in S variants of enterococci. The
      highest antibacterial activity was found in Sm variants of lactobacilli,
      especially in Lactobacillus sp. M76AT The latter is biotechnologically the most
      promising strain, since all variants fermented milk yielding the products with
      uniformly pronounced functional and organoleptic properties. These patterns are
      of importance for the understanding of the mechanisms of antibiotic resistance
      and for selection of the variants with desired properties, as well as for quality
      control of the lactic acid bacteria starter cultures.

PMID- 25844439
TI  - [Functional activity of the modA, gene in Methylobacterium dichloromethanicum
      DM4].
AB  - The putative METDI2644 (modA2) gene of Methylobacterium dichloromethanicum DM4,
      present in the 126-kbp chromosomal fragment associated with dichloromethane (DCM)
      degradation was investigated. While this gene is presumed to encode the
      periplasmic substrate-binding subunit of the molybdate ABC transporter, its
      conceptual translation also exhibits similarity to the proteins containing the
      ostA conservative domain and responsible for resistance of gram-negative bacteria
      to organic solvents. Reverse transcription polymerase chain reaction (RT-PCR)
      revealed the RNA transcripts of this gene in the cells grown on either DCM or
      methanol. The mobilizable suicide vector pK18mob was used to obtain a knockout
      mutant with the METDI2644 gene inactivated by insertion of the gentamycin
      cassette. The mutant pregrown on methanol exhibited lower growth rate on DCM than
      the wild-type strain DM4. The difference was not alleviated by addition of sodium
      molybdate. Our results suggest that the METDI2644 gene product plays a role in
      cell adaptation to DCM degradation.

PMID- 25844440
TI  - [Periplasmic lysozime inhibitior PliC and its role in antilysozime activity of
      enterobacteria].
AB  - Two families of specific inhibitors of type C lysozyme (Ivy and PliC) secreted
      from the periplasmic space are known in enterobacteria. Microbial capacity for
      distant lysozyme inactivation (antilysozyme activity) is most pronounced in the
      strains and species carrying homologues of the pliCgene. The pliC homologue
      localized in a -200-kbp megaplasmid of Klebsiella pneumoniae was shown to differ
      significantly in the amino acid composition of the coded polypeptide. Similar to
      the Salmonella enterica pliC homologue, it possesses a detachable signal part and
      contains identical functionally critical amino acids of the active center of the
      inhibitor. Antilysozyme activity of the pliC-positive K. pneumoniae strains was
      observed at the level corresponding to the highest values found inpliC-positive
      S. enterica. High level of the antilysozyme activity in K. pneumoniae strains
      containing the plasmid pliC homologue was found in all studied strains, unlike S.
      enterica strains carrying the known chromosomal pliC homologue.

PMID- 25844442
TI  - [Ribonucleolytic activity of mycoplasmas].
AB  - Mycoplasmas are incapable of de novo synthesis of nucleotides and must therefore
      secrete nucleases in order to replenish the pool of nucleic acid precursors. The
      nucleolytic activity of mycoplasmas is an important factor in their
      pathogenicity. Bacterial ribonucleases (RNases) may produce a broad spectrum of
      biological effects, including antiviral and antitumor activity. Mycoplasma RNases
      are therefore of interest. In the present work, capacity of Acholeplasma
      laidlawii and Mycoplasma hominis for RNase synthesis and secretion was studied.
      During the stationary growth phase, these organisms were found to synthesize
      Mg(2+)-dependent RNases, with their highest activity detected outside the cells.
      Localization of A. laidlawii RNases was determined: almost 90% of the RNase
      activity was found to be associated with the membrane vesicles. Bioinformational
      analysis revealed homology between the nucleotide sequences of 14 Bacillus
      subtilis genes encoding the products with RNase activity and the genes of the
      mycoplasmas under study. Amino acid sequences of 4 A. laidlawii proteins with
      ribonuclease activity and the Bsn RNase was also established.

PMID- 25844441
TI  - [Characterization, identification, and screening for tetrodotoxin production by
      bacteria associated with the Cephalotrix simula (Ivata, 1952) proboscis worm].
AB  - The taxonomic composition of bacteria associated with the Cephalotrix simula
      proboscis worm was studied and screening of the tetrodotoxin (TTX)-producing
      bacteria was carried out using confocal laser scanning microscopy and polyclonal
      antibodies. Bacterial isolates were identified using the 16S rRNA gene sequencing
      and phenotypic characteristics. A Bacillus species was found to be responsible
      for tetrodotoxin production in C. simula proboscis worms. Vibrio spp.
      predominated in the associated microflora (68.18% of the total number of
      isolates). Analysis of the sensitivity of 16 strains to antibiotics of various
      classes revealed multiple resistance to three or more antibiotics in all studied
      isolates. Poor growth of most of the isolates on all laboratory media was an
      indirect confirmation of the symbiotic relationships between the micro- and
      macroorganisms.

PMID- 25844444
TI  - [Comparative assessment of inductive effects of Azospirillum lectins with
      different antigenic properties on the signal systems of wheat seedling roots].
AB  - The lectins of associative nitrogen-fixing bacteria Azospirillum brasilense Sp7
      and its mutant A. brasilense Sp7.2.3 were shown to have different effects on the
      components of the wheat seedling root signal system, namely to regulate the
      levels of cAMP, nitric oxide, diacylglycerol, and salicylic acid, as well as to
      induce the activities of superoxide dismutase and lipoxygenase. Our results make
      it possible to consider azospirilla lectins as inducers of the signal systems in
      wheat seedling roots, since they cause development of several flows of primary
      signals. These data are of general biological importance, since lectins are
      present in all living organisms and most ot the functions of lectins remain
      insufficiently understood.

PMID- 25844443
TI  - [Effect of temperature on the rate of oxidation of pyrrhotite-rich sulfide ore
      flotation concentrate and the structure of the acidophilic chemolithoautotrophic
      microbial community].
AB  - Oxidation of flotation concentrate of a pyrrhotite-rich sulfide ore by
      acidophilic chemolithoautotrophic microbial communities at 35, 40, and 45 degrees
      C was investigated. According to the physicochemical parameters of the liquid
      phase of the pulp, as well as the results of analysis of the solid residue after
      biooxidation and cyanidation, the community developed at 40 degrees C exhibited
      the highest rate of oxidation. The degree of gold recovery at 35, 40, and 45
      degrees C was 89.34, 94.59, and 83.25%, respectively. At 40 degrees C, the
      highest number of microbial cells (6.01 x 10(9) cells/mL) was observed. While
      temperature had very little effect on the species composition of microbial
      communities, except for the absence of Leptospirillum ferriphilum at 35 degrees
      C, the shares of individual species in the communities varied with temperature.
      Relatively high numbers of Sulfobacillus thermosulfidooxidans, the organism
      oxidizing iron and elemental sulfur at higher rates than other acidophilic
      chemolithotrophic species, were observed at 40 degrees C.

PMID- 25844445
TI  - [Cryptomonad alga Rhodomonas sp. (Cryptophyta, Pyrenomonadaceae) bloom in the
      redox zone of the basins separating from the White Sea].
AB  - Bloom of a cryptomonad alga Rhodomonas sp. (Cryptophyta, Pyrenomonadaceae) was
      observed in the chemocline of saline basins separating from the White Sea,
      resulting in red coloration of the relevant water layer. According to the
      sequence of the 18S nuclear rRNA gene, this species was identical to Rhodomonas
      sp.RCC2020 (GenBank accession no. JN934672) from the Beaufort Sea. The presence
      of the red layer formed by mass development of Rhodomonas sp. is considered as an
      indicator of a certain stage of separation of a basin from the sea.

PMID- 25844446
TI  - [Microbial communities of the discharge zone of oil- and gas-bearing fluids in
      low-mineral Lake Baikal].
AB  - At the site of natural ingress of oil microbial diversity in the Central Baikal
      bottom sediments differing in the chemical composition of pore waters was studied
      by molecular biological techniques. The sediments saturated with oil and methane
      were found to contain members of 10 bacterial and 2 archaeal phyla. The oxidized
      sediment layer contained methanotrophic bacteria belonging to the
      Alphaproteobacteria, which had a specific structure of the pmoA gene and
      clustered together with uncultured methanotrophs from cold ecosystems. The upper
      sediment layer contained also oil-oxidizing bacteria and the alkB genes most
      colsely related to those of Rhodococcus. The microbial community of reduced
      sediments exhibited lower diversity and was represented mostly by the organisms
      involved in hydrocarbon biodegradation.

PMID- 25844447
TI  - [Isolation of a divergent strain of Candida saitoana from the Anyui mummy of a
      steppe bison (Bison priscus)].

PMID- 25844448
TI  - [In memorium I. S. Kulaev].

PMID- 25844449
TI  - [Antenna replacement in the evolutionary origin of chloroplasts].
AB  - Endosymbiotic origin of chloroplasts from unicellular cyanobacteria is presently
      beyond doubt. Oxygenic photosynthesis is based on coordinated action of two
      photosystems (PS), PS I and PS II, cooperating with several variants of the
      pigment antenna. In cyanobacteria, red algae, and glaucophytes, phycobilisomes
      (PBS) act as antennae, while in terrestrial plants, as well as most macro- and
      microalgae antennae are formed by chlorophyll a/b- and chlorophyll a/c-containing
      proteins. Advantages and disadvantages of the PBS antenna compared to other light
      gathering complexes form the basis for adaptive variations of the antenna in the
      course of development of eukaryotic photosynthesis. During the evolution of the
      "green" and "chromophyte" lineages of the chloroplasts, PBS, in spite of their
      optimal features of light absorption,were replaced by chlorophyll a/b- and
      chlorophyll a/c-containing light-gathering complexes. Development of the cell
      wall associated with limited motility and with tissue formation in photosynthetic
      eukaryotes were the factors responsible for the antenna shift. The subsequent
      redistribution of cell resources in favor of cellulose biosynthesis required
      increased for CO2 consumption, higher PS II levels, and greater number and
      density of the thylakoids in the chloroplasts, got incompatible with the energy
      consuming and overly large PBS antenna.

PMID- 25844450
TI  - [ATP pool and bioluminescence in psychrophilic bacteria Photobacterium
      phosphoreum].
AB  - Bioluminescence activity and ATP pool were investigated in the culture of
      psychrophilic bacteria Photobacterium phosphoreum collected-from the exponential
      and stationary growth phases, as well as immobilized in polyvinyl alcohol (PVA)
      cryogel. In liquid culture, ATP pool remained at an almost a constant level
      throughout the luminescence cycle (over 100 h). The ATP pool in the stationary
      phase and PVA-immobilizedl cells remained constant throughout their incubation in
      the medium (over 200 h) and in 3% NaCl solution (over 100 h): Quantitative
      assessment of integral photon yield and ATP pool indicated that bioluminescence
      decay in growing or stationary cells was not caused by limitation by the energy
      substrates of the luciferase reaction. Kinetic and quantitative parameters of
      emission activity and ATP pool excluded the possibility of formation of the
      aldehyde substrate for luciferase via reduction of the relevant fatty acids in
      NADPH and ATP-dependent reductase reaction and its oxidation in the monooxygenase
      reaction. Our results indicate that the aliphatic aldehyde is not utilized in the
      process of light emission.

PMID- 25844451
TI  - [metabolism of the phase variants of the phototrophic bacterium Rhodobacter
      sphaeroides].
AB  - Growth, bacteriochlorophyll a content, electron transport chain (ETC), and
      activities of the tricarboxylic acid (TCA) cycle enzymes were studied in R and M
      phase variants of Rhodobactersphaeroides cells grown anaerobically in the light
      and aerobically in the dark. Under all cultivation conditions tested,
      bacteriochlorophyll a content was 2-3 times lower in the cells of the M. variant
      compared to the R variant, which therefore was predominant in the cultures grown
      in the light. In both variants, activity of all TCA cycle enzymes was higher for
      the cells grown in the dark under aerobic conditions. When grown aerobically in
      the dark, the R variant, unlike the M variant, did not contain cytochrome aa3,
      acting as. cytochrome c oxidase, in its ETC. An additional point of coupling the
      electron transfer to the generation of the proton gradient al the cytochrome aa3
      level provided for more efficient oxidation of organic substrates, resulting in
      predominance of the M variant in the cultures grown in the dark under aerobic
      conditions.

PMID- 25844452
TI  - [Characterization of the lipopolysaccharides of serogroup II Azospirillum].
AB  - Lipopolysaccharides of six Azospirillum strains (A. brasilense SR50, SR80, SR88,
      SR109, SR111, SR115, and A. lipoferum SR 42) isolated from the rhizosphere of
      cereal plants of Saratov oblast, Russia and assigned to serogroup II by
      serological analysis were studied. In the lipid A fatty acid composition, the
      lipopolysaccharides under study were similar to those of other Azospirillum
      strains and were characterized by predominance of 3-hydroxytetradecanoic, 3
      hydroxyhexadecanoic, and octadecenoic acids. Monosaccharide analysis of the O
      specific polysaccharides (including determination of the absolute configurations,
      methylation analysis, and one- and two-dimensional NMR spectroscopy) revealed the
      presence of two types of repeating units in varying ratios. High degree of
      serological similarity between the strains under study was shown to result from
      the presence of repeating units with identical structure in their O antigens.

PMID- 25844454
TI  - [Changes in growth patterns and intracellular calcium concentrations in
      aspergillus awamori treated with amphotericin B].
AB  - Growth patterns and intracellular Ca2+ concentrations in the mutant strain
      Aspergillus awamori 66A, containing a recombinant aequorin gene were studied in
      the presence of a permeabilizing fungicidal agent amphotericin B. The cell
      response, i.e., changes in the growth and development of the fungus (initiation
      of spore germination, mycelial growth, and intensity ofsporulation) was dose
      dependent. Low concentrations of amphotericin B (2.5 microM) stimulated spore
      germination: the number of germinating spores was 2-3 times higher than in the
      control (without the fungicide). At higher amphotericin concentrations (20
      microM) spore germination was inhibited. Amphotericin B had a dose-dependent
      effect on mycelial growth and sporulation intensity on solid Vogel medium.
      Intracellular Ca2+ concentrations in the presence of amphotericin B were
      investigated using the luminescence of the photoprotein aequorin. High
      concentrations of amphotericin B (10 and 20 microM) were shown to cause an
      instantaneous increase in Ca2+ concentrations, compared to the control and lower
      amphotericin concentration (2.5 microM). Ca2+ concentrations remained elevated
      throughout the experiment and correlated with the inhibition of mycelial growth
      and development.

PMID- 25844453
TI  - [Relation between ligninolytic and phospholipase activities in the fungus
      Lentinus tigrinus].
AB  - Effect of hydrocortisone, NaF, and FeSO4 on ligninolytic and phosphatase activity
      of the fungus Lentinus (Panus) tigrinus VKM F-3616D was investigated,
      Hydrocortisone and NaF were shown to inhibit the enzymes of the ligninolytic
      complex-laccase (EC 1.10.3.2), secretory peroxidase (EC 1.11.1.7), and Mn
      peroxidase (EC 1.11.1.13). FeSO4 exhibited no significant effect on the activity
      of these enzymes. Decreased activity of the enzymes of the ligninolytic complex
      was associatedwith inhibition of the activity and changes in the substrate
      specificity of phospholipase A2 (EC 3.1.1.4) in the presence of hydrocortisone of
      NaF. Cultivation of L. tigrinus in the presence of these compounds resulted in
      higher affinity of this enzyme to saturated fatty acids, while in the control and
      in the presence of FeSO4 affinity to unsaturated fatty acids was higher.

PMID- 25844455
TI  - [New antibiotics produced by Bacillus subtilis strains].
AB  - Two Bacillus subtilis strains isolated from the fruiting body of a basidiomycete
      fungus Pholiota squarrosa exhibited a broad range of antibacterial activity,
      including those against methicillin-resistant Staphylococcus aureus INA 00761
      (MRSA) and Leuconostoc mes6nteroides VKPM B-4177 resistant to glycopep-> tide
      antibiotics, as well as antifungal activity. The strains were identified as
      belonging to the "B. subtilis" com- plex based on their morphological and
      physiological characteristics, as well as by sequencing of the 16S rRNA gene
      fragments. Both strains (INA 01085 and INA 01086) produced insignificant amounts
      of polyene antibiotics (hexaen and pentaen, respectively). Strain INA 01086
      produced also a cyclic polypeptide antibiotic containing Asp, Gly, Leu, Pro, Tyr,
      Thr, Trp, and Phe, while the antibiotic of strain INA 01085 contained, apart from
      these, two unidentified nonproteinaceous amino acids. Both polypeptide
      antibiotics were new compounds efficient against gram-positive bacteria and able
      to override the natural bacterial antibiotic resistance.

PMID- 25844456
TI  - [Comparison of biochemical and molecular genetic approaches for identification of
      environmental strains].
AB  - In order to confirm the taxonomic position of environmental strains determined
      based on their biochemical, cultural, andmorphological characteristics, molecular
      genetic identification was carried out. A number of problems in identification of
      microorganisms were shown to be associated with contamination of the cultures in
      the course of isolation. Advantages of a comprehensive approach, combining 16S
      rRNA gene sequencing with a set of biochemical, cultural, and morphological
      parameters; for identification of microorganisms isolated from environmental
      objects and clinical samples are discussed.

PMID- 25844457
TI  - [Roseibacula alcaliphilum gen. nov. sp. nov., a new alkaliphilic aerobic
      anoxygenic phototrophic bacterium from a meromictic soda Lake Doroninskoe (East
      Siberia, Russia)].
AB  - A bacterial strain De was isolated from the surface water layer of the meromictic
      soda lake Doroninskoe. When grown in the dark, it formed-pink colonies on agar
      media. The cells were nonmotile, contained bacteriochlorophyll a and carotenoids.
      Stationary-phase cells contained intracellular vesicular membranes similar to the
      membranes of the photosynthetic apparatus of some ndnsulfur purple bacteria.
      Aerobic growth did not occur. Sucrose, citrate, mannitol, sorbitol, case in
      hydrolysate,and yeast extract were the preferable substrates for aerobic growth,
      Xylose, lactose, aspartate, benzoate, malate, malonate, succinate, tartrate,
      formate, fumarate, glycerol, methanol, and ethanol were not utilized; Growth
      occurred at up to 50.g/L NaCl (optimum at 5 g/L) and pH 9.8. According to the 16S
      rRNA gene sequencing, similarity between the isolate and the known alkaliphilic
      genera of nonsulfur purple bacteria (Rhodobaca) and of aerobic anoxygenic
      phototrophic bacteria (Roseinatronobacter) was 96%, which was sufficient for
      description ofa new genus of aerobic anoxygenic phototrophic bacteria. The name
      Roseibacula alcaliphiluin gen. nov., sp. nov. was, proposed for the isolate.

PMID- 25844458
TI  - [Promising microbial consortia for producing biofertilizers for rice fields].
AB  - Two cyanobacterial cultures from rice paddies of Kyzylorda region, Kazakhstan
      were isolated and characterized: Anabaena variabilis and Nostoc calsicola. Based
      on these cultures, new consortia ofcyanobacteria, microalgae and Azotobacter were
      developed: ZOB-1 (Anabaena variabilis, Chlorella vulgaris, and Azotobacter sp.)
      and ZBOB-2 (Nostoc calsicola, Chlorella vulgaris, and Azotobacter sp.). High
      growth rate and photosynthetic activity of microalgae were observed in these
      consortia. The active consotrium ZOB-1 was selected, which improvd germination
      and growth of rice plants. ZOB-1 was recommended as a biostimulator and
      biofertilizer for crops.

PMID- 25844459
TI  - [Archaeal diversity in permafrost deposits of Bunger Hills Oasis and King George
      Island (Antarctica) according to the 16S rRNA gene sequencing].
AB  - Archaeal communities of permafrost deposits of King George Island and Bunger
      Hills Oasis (Antarctica) differing in the content of biogenic methane were
      analyzed using clone libraries of two 16S rRNA gene regions. Phylotypes belonging
      to methanogenic archaea were identified in all horizons.

PMID- 25844460
TI  - [Anoxygenic phototrophic bacteria from microbial communities of Goryachinsk
      Thermal Spring (Baikal Area, Russia)].
AB  - Species composition of anoxygenic phototrophic bacteria in microbial mats of the
      Goryachinsk thermal spring was investigated along the temperature gradient. The
      spring belonging to nitrogenous alkaline hydrotherms is located at the shore of
      Lake Baikal 188 km north-east from Ulan-Ude. The water is of the sulfate-sodium
      type, contains trace amounts of sulfide, salinity does not exceed 0.64 g/L, pH
      9.5. The temperature at the outlet of the spring may reach 54 degrees C. The
      cultures of filamentous anoxygenic phototrophic bacteria, nonsulfur and sulfur
      purple bacteria, and aerobic anoxygenic phototrophic bacteria were identified
      using the pufLM molecular marker. The fmoA marker was used for identification of
      green sulfur bacteria. Filamentous cyanobacteria predominated in the mats, with
      anoxygenic phototrophs comprising a minor component of the phototrophic
      communities. Thermophilic bacteria Chloroflexus aurantiacus were detected irn the
      samples from both the thermophilic and mesophilic mats. Cultures ofnonsulfur
      purple bacteria similar to Blastochloris sulfoviridis and Rhodomicrobium
      vannielii were isolatd from the mats developing at high (50.6-49.4 degrees C) and
      low temperatures (45-20 degrees C). Purple sulfur bacteria Allochromatium sp. and
      Thiocapsa sp., as well as green sulfur bacteria Chlorobium sp., were revealedin
      low-temperature mats. Truly thermophilic purple and gree sulfur bacteria were not
      found in the spring. Anoxygenic phototrophic bacteria found in the spring were
      typical of the sulfuret communities, for which the sulfur cycle is mandatory. The
      presence of aerobic bacteriochlorophylla-containing bacteria identified as
      Agrobacterium (Rhizobium) tumifaciens in the mesophilic (20 degrees C) mat is of
      interest.

PMID- 25844461
TI  - [Population structure of the clover rhizobia Rhizobium leguminosarum bv. trifolii
      upon transition from soil into the nodular niche].
AB  - High-throughput sequencing of the amplicon gene library revealed variations in
      the population structure of clover rhizobia (Rhizobium leguminosarum bv.
      trifolii) upon transition from soil into the root nodules of the host plant
      (Trifolium-hybridum). Analysis of rhizobial-diversity using the nodA gene
      revealed 3258 and 1449 nucleotide sequences (allelic-variants) for the soil and
      root nodule population, respectively. They were combined into 29 operational
      taxonomic units (OTU) according to the 97% identity level; 24 OTU were. foundin
      the soil population, 12 were present in the root nodulepopulation, and 7 were
      common. The predominant OTE13 (77.4 and 91.5% of the soil and root nodule
      populations, respectively) contained 155 and -200 variants of the soil and root
      nodule populations, respectively, with the nucleotide diversity increasing
      significantly upon the "soil-->root" transition. The "moving window" approach was
      used to reveal the sites of the nodA gene in which polymorphism, including that
      associated with increased frequency of non-synonymous substitution frequency,
      increased sharply upon transition from soil into root nodiles. PCR analysis of
      the IGS genotypes of individual strains revealed insignificant changes in
      rhizobial diversity upon transition from soil into root nodules. These results
      indicate that acceleration of rhizobial evolutioin in the course of symbiosis may
      be associated with development of highly polymorphic virulent:subpopulations
      subjected to directional selection in the "plant-soil" system.

PMID- 25844462
TI  - [Ca2+ signaling in prokaryotes].
AB  - The role of Ca2+ ions in the regulation of motility, cell cycle, and division of
      prokaryotes is dis- cussed, as well as their involvement in pathogenesis of come
      infectious diseases. The structural and functional organization of the
      prokaryotic Ca2+ signal system and the mechanisms of Ca2+ membrane transport and
      homeostasis are described. Special attention is paid to the role of Ca2+ cation
      channels, Ca2+ transporters, and Ca2+ -binding proteins in the regulation of the
      intercellular Ca2+ concentration.

PMID- 25844463
TI  - [Synthesis and localization of L-lactate oxidase in yeasts].
AB  - Conditions for L-lactate oxidase synthesis by the yeast Yarrowia lpolytica were
      investigated. The enzyme was found to be synthesized during growth on L-lactate
      in the exponential growth phase. L-lactate oxidase synthesis was observed, also
      on glucose after adaptation to stress conditions (oxidative or thermal stress) r
      during the stationary growth phase after glucose consumption. The cells grown on
      L-lactate exhibited high levels of antioxidant enzymes (catalase, superoxide
      dismutase, glucose-6-phosphate dehydrogenase, and glutathione reductase), which
      exceeded those of glucose-grown cells. The ultrastructure of L-lactate-grown
      cellsand of those grown on glucose and adapted to various stress.conditions was
      also found to besimilar, with increased mitochondria, elevated number and size
      ofperoxisomes, and formation of lipid and polyphosphate inclusions. In order to
      determine the intracellular localization of L-lactate oxidase, the cells were
      disintegrated by the lytic enzyme complex from Helix pomatia. Centrifugation of
      the homogenate in Percoll gradient resulted in the isolation of purified
      fractions of the native mitochondria and peroxisomes. L-Lactate oxidase was shown
      to be localized in peroxisomes.

PMID- 25844464
TI  - [Formation of organic acids by fungi isolated from the surface of stone
      monuments].
AB  - Capacity of the fungi isolated from the surface of stone monuments for acid
      formation was studied in cultures under various carbon sources and cultivation
      conditions. The composition of organic nutrients was adjusted according to the
      results of investigation of the surface layers from the monuments in urban
      environment. The primary soil formed at the surface of the stone monuments under
      urban conditions was shown to contain a variety of carbon and nitrogen sources
      and is a rich substrate for fungal growth. Oxalic acid was produced by fungi
      grown on media with various concentrations of sugars, sugar alcohols, and organic
      acids. Malic, citric, fumaric, and succinic acids were identified only at
      elevated carbohydrate concentrations, mostly in liquid cultures. Oxalic acid was
      the dominant among the acids produced by Aspergillus niger at all experimental
      setups. Unlike A. niger, the relative content of oxalic acid produced by
      Penicillium citrinum decreased at high carbohydrate concentrations.

PMID- 25844465
TI  - [Biological activity of fungi from the phyllosphere of weeds and wild herbaceous
      plants].
AB  - Antimicrobial, phytotoxic, and insecticidal activity of 30 fungal isolates
      obtained from leaves of weeds and wild herbaceous plants was assessed.
      Antibacterial, antifungal, phytotoxic, and insecticidal activity was found in
      over 50, 40, 47, and 40% of the isolates, respectively. These findings may be
      important for toxicological assessment of potential mycoherbicides, as well as
      provide a basis for investigation of the patterns of development of phyllosphere
      communities affected by fungal metabolites.

PMID- 25844466
TI  - [Auxin production by Klebsiella planticola strain TSKhA-91 and Its Effect of
      development of cucumber (Cucumis sativus L.) Seeds].
AB  - Capacity of Klebsiella planticola strain TSJhA-91 for synthesis of indolyl-3
      acetic acid (IAA) and other auxins was studied. The qualitative and quantitative
      composition of these compounds depends on the presence of exogeneous tryptophan
      and on the nitrogen source. The highest IAA yield was obtained at the stationary
      phase of growth. Addition of L-tryptophan to the medium resulted in a significant
      increase (up to 85.5 microg/mL) of auxin biosynthesis, especially in the presence
      of nitrates. Thin-layer chromatography revealed that the indole-3-acetamide
      pathway was not active in this strain. The biological activity of auxins was
      confirmed by plant assay with the kidney bean cuttings; the height of root
      formation and rdot number increased 16- and 6-fold, respectively. Under
      conditions of low-temperature stress, protective effect of K. planticola TSKhA-91
      on development of cucumbers (Cucumissativus L.) seeds, including stimulation of
      germi- nation and root formation by its seeds were shown.

PMID- 25844467
TI  - [Thermoacidophilic micirobial community oxidizing the gold-bearing flotation
      concentrate of a pyrite-arsenopyrite ore].
AB  - An aboriginal community of thermophilic acidophilic chemolithotrophic
      microorganisms (ACM) was isolated from a sample of pyrite gold-bearing flotation
      concentrateat 45-47 degrees C and pH 1.8-2.0. Compared to an experimental
      thermoacidophilic microbial consortium formed in the course of cultivation in
      parallel bioreactors, it had lower rates of iron leaching and oxidation, while
      its rate of sulfur oxidation was higher. A new thermophilic acidophilic microbial
      community was obtained by mutual enrichment with the micioorganisms from thie
      experimental and aboriginal communities during oxidation of sulfide ore flotation
      concentrate at 47 degrees C. The dominant bacteria of this new ACM community were
      Acidithiobacillus caldus strains (the most active sulfur oxidizers) and
      Sulfobacillus thermotolerans strains (active oxidizers of both iron and sulfur),
      while iron-oxidizing archaea of the family Ferroplasmaceae and heterotrophic
      bacteria Alicyclobacillus tolerans were the minor components. The new ACM
      community showed promise for leaching/oxidation of sulfides from flotation
      concentrates at high pulp density (S:L = 1:4).

PMID- 25844468
TI  - [Optimization of bioleaching and oxidation of gold-bearing pyrite-arsnopyrite ore
      concentrate in batch mode].
AB  - Biooxidation of refractory gold-bearing pyrite-arsenopyrite flotation concentrate
      was optimized and aburidance of predominant groups in the community
      ofthermophilic acidophilic chemolithotrophic microorganisms at various stages
      ofbioleaching was determined. The optimal parameters for growth and
      leaching/oxidation of the mineral components of the concentrate were pSH 1.4, 1.6
      1.8; 47.5 degrees C; and the following salt concentrations in the liquid phase
      (g/L): K2HPO4.3H2O, 0.53; (NH4)2SO4, 1.6 and MgSO4.7H2O, 2.5 (or (NH4)2SO4, 1.23;
      ammophos, 0.41; KOH, 0.1) with 0.03% yeast extract. The optimal conditions
      resulted in high growth rate, high levels of iron andarsenic leaching, of Fe2+
      and S(2-)/S0 oxidation, and predominance of Acidithiobacillus caldus,
      Sulfobacillus spp., and Ferroplasma spp. in the community.

PMID- 25844469
TI  - [transversion of cell polarity from Bi- to multipolarity is the mechanism
      determining multiple spore formation in Anaerobacter polyendosporus PS-1T].
AB  - The number of spores formed in a single cell ofAnaerobacterpolyendosporus PS-1T
      is significantly influenced by the composition of nutrient media. Depending on
      carbohydrate concentration in synthetic medium, the number of spores may vary
      from one-two to five-seven. Investigation of spore formation by fluorescence and
      electron microscopy revealed that on media with 0.5-1.0% glucose or galactose
      most of the vegetative cells remained rod-shaped after cessation of cell division
      in the culture. Their nucleoids were localized at cell poles close to the polar
      site of the cytoplasmic membrane. Forespores were formed at one or both of these
      poles. A satellite nucleoid (operator) was detected close to each forespore. In
      the variant with bipolar organization of mother cells only one or two spores per
      cell were formed. In the second variant of cultivation, when the cells grew at
      low galactose concentrations (0.1-0.3%), most of the vegetative cells increased
      in volume and became oval or spherical after cessation of cell division in the
      culture. Epifluorescence microscopy with nucleic acids-specific fluorochromes
      (DAPI and acridine orange) revealed the presence of multiple (six to nine)
      nucleoids in these cells. The nucleoids were located at the cell periphery in
      close contact with the cytoplasmic membrane. These nucleoids became the centers
      (poles) for forespore formation. Thus, in the early stationary phase transversion
      from bipolar to multipolar cells occurred during the early stationary phase.
      Cessation of cell division combined with continuing replication of the nucleoids
      resulted in formation on multinuclear cells. The multiplicity of nucleoides and
      multipolarity of these cells were prerequisites determining endogenous
      polysporogenesis, occurring as synchronous formation of three to seven twin
      spores in a number of the oval and spherical cells.

PMID- 25844471
TI  - [Comparison of the fungal complexes of the Japanese scallop Mizuhopecten
      yessoensis (Jay, 1856) from different areas of the Peter the Great Bay, Sea of
      Japan].
AB  - Mycological investigation of the Japanese scallop Mizuhopecten yessoensis (Jay)
      (Bivalvia) collected in different areas of the Peter the Great Bay, Sea of Japan,
      was carried out. A total of 72 species of filamentous fungi belonging to 30
      genera of ascomycetes, anamorphous fungi, and zygomycetes was isolated from the
      internal organs of the scallop. The species.diversity of mycelial fungi in the
      internal organs, especially of members of the generaAspergillus, Penicillium,
      Cladosporium, and Chaetomium, was found to increase in polluted coastal waters.

PMID- 25844470
TI  - [Diversity of diazotrophs in the sediments of hypersaline salt and soda lakes
      analyzed with the use of the nifH gene as a molecular marker].
AB  - Phylogenetic analysis of the nifH genes, encoding the Fe protein of the
      nitrogenas enzymatic complex, was carried out for pure cultures of anoxygenic
      phototrophic bacteria of diverse origin, as well as for heterotrophic
      alkaliphilic sulfate reducers isolated from saline and soda lakes. Topology of
      the nitrogenase tree correlated with that of the 16S rRNAgene tree to a
      considerable degree; which niade it possible to use the nifH gene as a molecular
      marker for investigation of diazotrophic bacterialcommunities in silty sediments
      of saline and sodalakes. Although diazotrophs were revealed in all
      environmentalsamples, their phylogenetic diversity was relatively low. Sulfate
      reducing deltaproteobacteria and photo- and chemotrophicgammaproteobacteria were
      predominant in samples integrated over sediment thickness. Analysis of samples
      fromthe upper sediment layers revealed predominance of phototrophic diazotrophs
      of various phyla, including purple sulfur and nonsulfur proteobacteria, green
      nonsulfur bacteria, heliobacteria; and cyanobacteria. Some phylotypes could not
      be identified, probably indicating the presence of bacterial groups which have
      not yet been studied by conventional microbiological techniques.

PMID- 25844472
TI  - [Report of Quambalaria cyanescens associated with birch].
AB  - Long-term microbiological investigation of the pollen of silver birch (Betula
      pendula) in the Mos- cow, and Moscow region areas revealed that: almost one-third
      of the analyzed samples, contained the fungus identified by morphological,
      cultural, and molecular genetic techniques as Quambalaria cyanescens (de Hoog &
      G. A. de Vries) Z.W. de Beer, Begerow & R. Bauer. This species was previously
      known mostly as a syrmbiont of tropical plants of the generaEucalyptus and
      Cortyminbia and has not been isolated in Russia. We revealed a close association
      between Quambalaria cyanescens and silver birch. The micromycete was regulaly
      detected in pollen samples, as well as on the.inside and outside of the aments,
      on the surface of leaves and branches. It was never isolated from other plant
      species in the investigated area. The data on the morphological and cultural
      characteristics of the fungus, its cell ultrastructure, and occurrence are
      presented, as well as the phylogenetic analysis of the isolated strains.

PMID- 25844473
TI  - [Microbial composition of the activated sludges of the Moscow wastewater
      treatment plants].
AB  - The contribution of the major technologically important microbial groups
      (ammonium- and nitrite-oxidizing, phosphate-accumulating, foam-inducing, and
      anammox bacteria, as well as planctomycetes and methanogenic archaea) was
      characterized for the aeration tanks of the Moscow wastewater treatment
      facilities. FISH investigation revealed that aerobic sludges were eubacterial
      communities; the metabolically active archaea contributed insignificantly. Stage
      II nitrifying microorganisms and planctomycetes were significant constituents of
      the bacterial component of activated sludge, with Nitrobacter spp. being the
      dominant nitrifier. No metabolically active anammox bacteria were revealed in the
      sludge from aeration tanks. The sludge from the aeration tanks using different
      wastewater treatment technologies were found to differ in characteristics.
      Abundance of the nitrifying and phosphate-accumulating bacteria in the sludges
      generally correlated with microbial activity, in microcosms and with efficiency
      of nitrogen and phosphorus removal from wastewater. The highest microbial numbers
      and activity were found in the sludges of the tanks operating according to the
      technologies developed in the universities of Hanover and Cape Town. The
      activated sludge from the Novokur yanovo facilities, where abundant growth of
      filamentous bacteria resulted in foam formation, exhibited the lowest activity
      The group of foaming bacteria included Gordonia spp. and Acinetobacter spp.,
      utilizing petroleum and motor oils, Sphaerotilus spp. utilizing unsaturated fatty
      acids, and Candidatus 'Microthrix parvicella'. Thus, the data on abundance and
      composition of metabolically active microorganisms obtained by FISH may be used
      for the technological control of wastewater treatment.

PMID- 25844474
TI  - [Molecular genetic identification of microcystin-producing cyanobacterial taxa in
      Lake Nero (Russia)].

PMID- 25844475
TI  - [Correction of hydrodynamic disorders in severe alcohol poisoning in adolescent].
AB  - OBJECTIVE: To improve the results of treatment of children with severe alcohol
      poisoning as a result of investigation of water sectors of the body. METHODS: The
      study included 54 patients aged from 13 to 15 years with a diagnosis of acute
      severe alcohol poisoning. All patients were divided into three groups. At the
      initial examination was determined the concentration of alcohol in saliva using
      Express-test "Alkoskan." Bioimpedance analysis was performed; water sectors of
      the body were investigated by analyzer of the balance of water sectors ABC-01
      "Medass." The study was conducted at the time of admission, after 12, 24 and 48
      hours. RESULTS: In severe alcohol poisoning at the time of admission, it was
      revealed a reduction of the fluid in all studied sectors. The most effective
      compensation of liquid was observed in groups, where was used combination therapy
      included intravenous fluids based 4.0 ml/kg/hour. CONCLUSION: The treatment of
      severe alcohol poisoning should include fluid resuscitation about 4 ml/kg/hour.
      This capacity of medical care give the ability to correct adequately the water
      sectoral disturbances already in the first 12 hours of hospitalization, and the
      inclusion to the basic therapy reamberine can contribute more effective
      replenishment of water sectors.

PMID- 25844476
TI  - [Effect of anesthesia in prevention of postoperative nausea and vomiting after
      surgical interventions in the nasal cavity and nasopharynx in children].
AB  - The article deals with results of studying of anesthesia effects on the frequency
      of postoperative nausea and vomiting during surgical interventions in the nasal
      cavity and nasopharynx in children. We investigated the incidence of
      postoperative nausea and vomiting in 100 patients aged 2 to 17 years (ASA I-II),
      who underwent surgery in the nasal cavity and nasopharynx. The results showed
      that the anesthesia by sevoflurane with nitrous oxide, local anesthetic lidocaine
      4 mg/kg, not more than 200 mg by nebulizer was accompanied by the development of
      postoperative nausea and vomiting in 4% of cases. In another hand, anesthesia by
      sevoflurane, nitrous oxide and fentanyl 2-3 mg/kg was accompanied with nausea and
      vomiting in 18% cases. Analysis of the results showed that the frequency of
      postoperative nausea and vomiting after anaesthesia without fentanyl by 14% lower
      than with fentanyl. The nausea and vomiting started within the first hour after
      surgery in majority number of cases (50-77.7%).

PMID- 25844477
TI  - [Causes of mortality and severity of state in newborns with inborn defects].
AB  - There is significant decrease in mortality rate of newborns with system
      dysfunction after development of perinatal centers in Russia. But in children
      with small gestational age and severe inborn defects the mortality rate is still
      high. Main causes of mortality and severity are: multiorgan failure, immaturity,
      infections (virus and/or bacteria, fungi). Severity of patient's condition
      strongly correlates with inflammation markers. Other factors effecting on
      mortality rate and probability of complication in postoperative period, are
      appearance of resistant microbes in premature babies and inability to total
      elimination of infectious source.

PMID- 25844478
TI  - [Enteral oxygenation in complex treatment of anaerobic septic shock in postpartum
      woman].
AB  - Purpose of the clinical case demonstration is to attract the professionals'
      attention to the method of enteral oxygen therapy successfully used in the
      complex intensive therapy of septic shock in young postpartum woman.

PMID- 25844480
TI  - Radical cyclization of epoxy vinyl- and allylsulfones promoted by titanocene
      chloride.
AB  - A titanocene-mediated intramolecular radical addition of different epoxy vinyl-
      and allylsulfones has been achieved. Five- and six-membered ring products were
      obtained in good to excellent yields in the presence of both 2.2 and 0.2 equiv of
      Cp2TiCl. A novel double-activation strategy allowed us to achieve small-size
      rings such as cyclobutanes and cyclopropanes. 

PMID- 25844481
TI  - In Vitro Studies on Degradation of Gamma-L-Glutamyl-L-Cysteine and Gamma-L
      Glutamyl-D-Cysteine in Blood: Implications for Treatment of Stroke.
AB  - Treatment for ischemic stroke involves a thrombolytic agent to re-establish blood
      flow in the brain. However, delayed reperfusion may cause injury to brain
      capillaries. Previous studies indicate that the antioxidant gamma-L-glutamyl-L
      cysteine (gamma-Glu-Cys) contributes to reducing reperfusion injury to the
      cerebral vasculature in rats, when administered intravascularly. To determine the
      stability of gamma-Glu-Cys in blood, the peptide was incubated in rat serum in
      vitro, and its degradation was quantified by high-pressure liquid chromatography.
      The half-time (t1/2) for degradation of gamma-Glu-Cys was 11 +/- 1 minute (mean
      +/- SD, n = 3). A similar pattern of degradation was observed when gamma-Glu-Cys
      was incubated in the presence of human plasma (t1/2 = 17 +/- 8 minutes, n = 3).
      In a second series of experiments, degradation of an analog (gamma-Glu-D-Cys) was
      tested in rat serum and found to be more stable than the native molecule. The
      initial velocity for degradation of gamma-Glu-D-Cys (0.12 +/- 0.02 mM/min; mean
      +/- SD, n = 3) was significantly (P = 0.006) less than that of gamma-Glu-Cys
      (0.22 +/- 0.03 mM/min; mean +/- SD, n = 3). Furthermore, an in vitro assay
      indicated that the analog has as an oxidative capacity that equals that of the
      original peptide in the presence of rat serum and human plasma. Finally, both
      peptides were found to be similarly effective in preventing lysis of intact cells
      using in vitro assays. These studies show that gamma-Glu-Cys remains intact in
      blood for several minutes, and the analog gamma-Glu-D-Cys may be a more stable,
      but similarly effective antioxidant. 

PMID- 25844479
TI  - The effect of ghrelin upon the early immune response in lean and obese mice
      during sepsis.
AB  - INTRODUCTION: It is well established that obesity-related hormones can have
      modulatory effects associated with the immune response. Ghrelin, a hormone mainly
      derived from endocrine cells of the gastric mucosa, regulates appetite, energy
      expenditure and body weight counteracting leptin, a hormone mainly derived from
      adipocytes. Additionally, receptors of both have been detected on immune cells
      and demonstrated an immune regulatory function during sepsis. METHODS: In the
      present study, the effect of peripheral ghrelin administration on early immune
      response and survival was investigated with lean mice and mice with diet-induced
      obesity using cecal ligation and puncture to induce sepsis. RESULTS: In the obese
      group, we found that ghrelin treatment improved survival, ameliorated
      hypothermia, and increased hyperleptinemia as compared to the lean controls. We
      also observed that ghrelin treatment divergently regulated serum IL-1beta and TNF
      alpha concentrations in both lean and obese septic mice. Ghrelin treatment
      initially decreased but later resulted in increased bacteriaemia in lean mice
      while having no impact upon obese mice. Similarly, ghrelin treatment increased
      early neutrophil oxidative burst while causing a decrease 48 hours after sepsis
      inducement. CONCLUSION: In conclusion, as the immune response to sepsis
      temporally changes, ghrelin treatment differentially mediates this response.
      Specifically, we observed that ghrelin conferred protective effects during the
      early phase of sepsis, but during the later phase deteriorated immune response
      and outcome. These adverse effects were more pronounced upon lean mice as
      compared to obese mice.

PMID- 25844482
TI  - Efficacy of Bisphosphonates on Bone Mineral Density and Fracture Rate in Patients
      With Osteogenesis Imperfecta: A Systematic Review and Meta-analysis.
AB  - Epidemiological evidence suggests that bisphosphonates are the most promising
      drugs for patients with osteogenesis imperfecta (OI). However, data on this issue
      are controversial. We conducted a meta-analysis to assess the efficacy of
      bisphosphonates on bone mineral density (BMD) and fracture rate in patients with
      OI. Electronic databases were searched to find relevant studies. Two reviewers
      independently identified relevant randomized controlled trials, which evaluated
      the efficacy of bisphosphonates in patients with OI. Outcome measures were
      fracture incidence and BMD changes in different skeletal sites. A total of 9
      randomized controlled trials including 557 patients were identified. Meta
      analysis demonstrated a beneficial effect of bisphosphonates on spine BMD Z-score
      and area BMD (in grams per square centimeter) %. Patients treated with
      bisphosphonates had a lower risk of fracture [risk ratio (RR) = 0.80; 95%
      confidence interval (CI): 0.66-0.97] compared with those in control groups. In
      children, bisphosphonates were efficacious in reducing fractures (RR = 0.80; 95%
      CI: 0.66-0.97), where in adults, bisphosphonates seemed equivalent to placebo in
      that respect (RR = 0.82; 95% CI: 0.42-1.59), although no significant difference
      was noted between these 2 RRs (test of interaction, z = -0.07; P = 0.94). There
      was also no significant difference in reducing fractures between oral and
      intravenous bisphosphonates (P = 0.23). This study showed that bisphosphonates
      could increase the BMD and reduce the risk of facture in patients with OI. There
      was no enough evidence to identify any differences in efficacy between oral and
      intravenous bisphosphonates on fracture reduction, as well as between children
      and adults. 

PMID- 25844483
TI  - Vertically aligned sulfur-graphene nanowalls on substrates for ultrafast lithium
      sulfur batteries.
AB  - Although lithium-sulfur batteries have gained great interest owing to their high
      energy density, they lack suitable electrodes capable of rapid charging and
      discharging to enable a high power density critical for wide applications. Here,
      we demonstrate a simply electrochemical assembly strategy to achieve vertically
      aligned sulfur-graphene (S-G) nanowall onto electrically conductive substrates.
      Remarkably, in each individual S-G nanowalls, sulfur nanoparticles are
      homogeneously anchored in between of graphene layers and ordered graphene arrays
      arrange perpendicularly to the substrates, which are favorable for the fast
      diffusions of both lithium and electron. Moreover, the hierarchical and porous
      structures facilate the effective accommodation of the volume change of sulfur.
      As a consequence, a high reversible capacity of 1261 mAh g(-1) in the first cycle
      and over 1210 mAh g(-1) after 120 cycles with excellent cyclability and high-rate
      performance (over 400 mAh g(-1) at 8C, 13.36 A g(-1)) are achieved with these S-G
      nanowalls as cathodes for lithium-sulfur batteries, providing the best reported
      rate performance for sulfur-graphene cathodes to date. 

PMID- 25844484
TI  - Special focus on autophagy.

PMID- 25844485
TI  - Retraction of Characterization of hydroxymethylation patterns in the promoter of
      beta-globin clusters in murine fetal livers (DOI: 10.1089/dna.2014.2773).

PMID- 25844486
TI  - Controllably Interfacing with Ferroelectric Layer: A Strategy for Enhancing Water
      Oxidation on Silicon by Surface Polarization.
AB  - Silicon (Si) is an important material in photoelectrochemical (PEC) water
      splitting because of its good light-harvesting capability as well as excellent
      charge-transport properties. However, the shallow valence band edge of Si hinders
      its PEC performance for water oxidation. Generally, thanks to their deep valence
      band edge, metal oxides are incorporated with Si to improve the performance, but
      they also decrease the transportation of carriers in the electrode. Here, we
      integrated a ferroelectric poly(vinylidene fluoride-trifluoroethylene) [P(VDF
      TrFE)] layer with Si to increase the photovoltage as well as the saturated
      current density. Because of the prominent ferroelectric property from P(VDF
      TrFE), the Schottky barrier between Si and the electrolyte can be facially tuned
      by manipulating the poling direction of the ferroelectric domains. The
      photovoltage is improved from 460 to 540 mV with a forward-poled P(VDF-TrFE)
      layer, while the current density increased from 5.8 to 12.4 mA/cm(2) at 1.23 V
      bias versus reversible hydrogen electrode. 

PMID- 25844487
TI  - Chemistry and related properties of freshly emitted sea spray aerosol.

PMID- 25844488
TI  - Evidence-Based Practice among Romanian Social Workers: Attitudes, Utilization,
      and Barriers.
AB  - In this article the authors report on a small survey of Romanian social workers
      regarding their attitudes toward evidence-based practice (EBP) and thoughts on
      the factors affecting its implementation in their clinical work. Eighty social
      workers were asked to complete a pen-and-paper questionnaire on their attitudes
      toward EBP, the use of research, and perceived barriers on implementation. Social
      workers have generally positive attitudes toward EBP. Insufficient time surfaced
      as the greatest barrier to successful implementation. Previous training during
      academic programs on the EBP foundations was associated with more positive
      attitudes and beliefs and also with stronger commitment toward implementation.
      Given the constant pressure that the limited resources pose on the social
      services, practitioners from the social work field must assure that their clients
      will have access to the best available programs and interventions. However, as
      the transfer of research into practice appears more complex than EBP suggests,
      the authors sought to understand how professionals construct their attitudes,
      level of commitment, and barriers. 

PMID- 25844489
TI  - Selectivity and anti-Parkinson's potential of thiadiazolidinone RGS4 inhibitors.
AB  - Many current therapies target G protein coupled receptors (GPCR), transporters,
      or ion channels. In addition to directly targeting these proteins, disrupting the
      protein-protein interactions that localize or regulate their function could
      enhance selectivity and provide unique pharmacologic actions. Regulators of G
      protein signaling (RGS) proteins, especially RGS4, play significant roles in
      epilepsy and Parkinson's disease. Thiadiazolidinone (TDZD) inhibitors of RGS4 are
      nanomolar potency blockers of the biochemical actions of RGS4 in vitro. Here, we
      demonstrate the substantial selectivity (8- to >5000-fold) of CCG-203769 for RGS4
      over other RGS proteins. It is also 300-fold selective for RGS4 over GSK-3beta,
      another target of this class of chemical scaffolds. It does not inhibit the
      cysteine protease papain at 100 MUM. CCG-203769 enhances Galphaq-dependent
      cellular Ca(2+) signaling in an RGS4-dependent manner. TDZD inhibitors also
      enhance Galphai-dependent delta-OR inhibition of cAMP production in SH-SY-5Y
      cells, which express endogenous receptors and RGS4. Importantly, CCG-203769
      potentiates the known RGS4 mechanism of Galphai-dependent muscarinic bradycardia
      in vivo. Furthermore, it reverses raclopride-induced akinesia and bradykinesia in
      mice, a model of some aspects of the movement disorder in Parkinson's disease. A
      broad assessment of compound effects revealed minimal off-target effects at
      concentrations necessary for cellular RGS4 inhibition. These results expand our
      understanding of the mechanism and specificity of TDZD RGS inhibitors and support
      the potential for therapeutic targeting of RGS proteins in Parkinson's disease
      and other neural disorders. 

PMID- 25844490
TI  - Adjustment enhancer or moderator? The role of resilience in postmigration filial
      responsibility.
AB  - The current study investigated resilience factors in filial responsibility and
      their relationships to adjustment indicators. Young adult immigrants from the
      former Soviet Union to Israel (N = 220) completed the Comprehensive Filial
      Responsibilities Inventory and 4 proxy measures of adjustment: An adapted version
      of the Brief Symptom Inventory, the Satisfaction With Life Scale, the General
      Self-Efficacy Scale, and selected items from the General Life Functioning
      Inventory. The resilience factors examined included individual characteristics of
      Sense of Coherence, Optimism, and perceived social support from an adapted
      version of the Multidimensional Scale of Perceived Social Support. In general,
      the resilience factors diminished the relationship between filial responsibility
      and some of the adjustment indicators. Overall, resilience factors make a strong
      and meaningful contribution to young immigrants' adjustment when main effects are
      considered. However, the resilience factors did not moderate the effect of filial
      responsibility in a protective way. The results contribute to an understanding of
      interrelations between postmigration filial responsibility and adjustment.
      Implications for social and clinical work with young-adult immigrants who have
      experienced filial responsibility in their family of origin are addressed.

PMID- 25844491
TI  - Over-time associations among parental self-efficacy, promotive parenting
      practices, and adolescents' externalizing behaviors.
AB  - Parental self-efficacy (PSE) is defined as parents' beliefs about their abilities
      to influence their children in a way that fosters their children's positive
      development. Research has shown links among PSE, parenting, and children's
      behavior (Jones & Prinz, 2005), but there are still questions concerning the
      associations over time. Theory predicts 3 types of processes relevant to these
      associations: a PSE-driven process, a parent-behavior-driven process, and a child
      driven process. In this study, we tested these processes during early to middle
      adolescence using reports from 401 parents (286 mothers, 115 fathers) from 305
      families, and their adolescents (Mage = 11.5 years), at 3 time points. Cross
      lagged panel models were used to examine the associations among PSE, promotive
      parenting practices, and adolescents' externalizing. Results supported a PSE
      driven process for mothers within early adolescence. In addition, evidence for
      parent-behavior-driven and child-driven processes emerged at different times
      within this developmental period.

PMID- 25844492
TI  - Prevention effects on trajectories of African American adolescents' exposure to
      interparental conflict and depressive symptoms.
AB  - The present study investigates the trajectory of children's exposure to
      interparental conflict during adolescence, its effects on adolescents'
      psychological adjustment, as well as the ability of a family-centered prevention
      program to alter this trajectory. A total of 331 African American couples with an
      adolescent or preadolescent child participated in a randomized control trial of
      the Promoting Strong African American Families program, a newly developed program
      targeting couple and cocaregiving processes. Using a multi-informant, latent
      growth curve approach, child exposure to interparental conflict during
      adolescence was found to be stable over a period of 2 years among families in the
      control group, but significantly declined among families in the treatment
      condition. Rates of change were significantly different between intervention and
      control groups based on parents' report of youth exposure to interparental
      conflict, but not for child's report. Structural equation models found trajectory
      parameters of interparental conflict predicted changes in adolescent depressive
      symptoms, with increasing rates of changes in conflict associated with increases
      in adolescent internalizing symptoms over the 2-year duration of the study.
      Finally, a significant indirect effect was identified linking treatment, changes
      in parents' reports of child exposure to interparental conflict, and adolescent
      depressive symptoms. The implications for research and intervention are
      discussed.

PMID- 25844493
TI  - Two-year outcomes of the Early Risers prevention trial with formerly homeless
      families residing in supportive housing.
AB  - This article reports 2-year outcomes from a cluster randomized, controlled trial
      of the Early Risers (ER) program implemented as a selective preventive
      intervention in supportive housing settings for homeless families. Based on the
      goals of this comprehensive prevention program, we predicted that intervention
      participants receiving ER services would show improvement in parenting and child
      outcomes relative to families in treatment-as-usual sites. The sample included
      270 children in 161 families, residing in 15 supportive housing sites;
      multimethod, multi-informant assessments conducted at baseline and yearly
      thereafter included parent and teacher report of child adjustment, parent report
      of parenting self-efficacy, and parent-child observations that yielded scores of
      effective parenting practices. Data were modeled in HLM7 (4-level model
      accounting for nesting of children within families and families within housing
      sites). Two years' postbaseline, intent-to-treat (ITT) analyses indicated that
      parents in the ER group showed significantly improved parenting self-efficacy,
      and parent report indicated significant reductions in ER group children's
      depression. No main effects of ITT were shown for observed parenting
      effectiveness. However, over time, average levels of parenting self-efficacy
      predicted observed effective parenting practices, and observed effective
      parenting practices predicted improvements in both teacher- and parent-report of
      child adjustment. This is the first study to our knowledge to demonstrate
      prevention effects of a program for homeless families residing in family
      supportive housing.

PMID- 25844494
TI  - Can mindful parenting be observed? Relations between observational ratings of
      mother-youth interactions and mothers' self-report of mindful parenting.
AB  - Research on mindful parenting, an extension of mindfulness to the interpersonal
      domain of parent-child relationships, has been limited by its reliance on self
      report assessment. The current study is the first to examine whether
      observational indices of parent-youth interactions differentiate between high and
      low levels of self-reported mindful parenting. The Iowa Family Interaction Rating
      Scales (IFIRS) were used to code interactions between mothers and their 7th grade
      youth. Mothers drawn from the top and bottom quartiles (n = 375) of a larger
      distribution of self-reported interpersonal mindfulness in parenting (N = 804)
      represented clearly defined high- and low-mindful parenting groups. Discriminant
      function analysis (DFA) was used to analyze how well 6 composite IFIRS
      observational rating variables (e.g., parental warmth, consistent discipline)
      discriminated between high and low self-reports of mindful parenting. DFA results
      were cross-validated, with statistically significant canonical correlations found
      for both subsamples (p < .05). Subsequent independent samples t tests revealed
      that group means were significantly different on all 6 IFIRS composite ratings.
      Confirmation of the relations between self-report mindful parenting and the
      observational ratings was also provided through hierarchical regression analyses
      conducted with a continuous predictor of mindful parenting using the full sample.
      Thus, the present study provides preliminary evidence for a link between self
      reported mindful parenting and observed interactions between parents and youth.

PMID- 25844495
TI  - Parental criticism is an environmental influence on adolescent somatic symptoms.
AB  - Previous studies have suggested that parental criticism leads to more somatic
      symptoms in adolescent children. However, this research has not assessed the
      direction of causation or whether genetic and/or environmental influences explain
      the association between parental criticism and adolescent somatic symptoms. As
      such, it is impossible to understand the mechanisms that underlie this
      association. The current study uses the Extended Children of Twins design to
      examine whether parents' genes, adolescents' genes, and/or environmental factors
      explain the relationship between parental criticism and adolescent somatic
      symptoms. Participants came from 2 twin samples, including the Twin and Offspring
      Study in Sweden (N = 868 pairs of adult twins and each twin's adolescent child)
      and from the Twin Study of Child and Adolescent Development (N = 690 pairs of
      twin children and their parents). Findings showed that environmental influences
      account for the association between parental criticism and adolescent somatic
      symptoms. This suggests that parents' critical behaviors exert a direct
      environmental effect on somatic symptoms in adolescent children. Results support
      the use of intervention programs focused on parental criticism to help reduce
      adolescents' somatic symptoms.

PMID- 25844497
TI  - Salivary cortisol responses to household tasks among couples with unexplained
      chronic fatigue.
AB  - This study examined salivary cortisol levels in couples in which one member had
      unexplained chronic fatigue (CF). The couples completed questionnaires and seven
      household activities in a laboratory setting and provided salivary cortisol
      samples prior to and immediately after the activities, as well as again after
      completing additional questionnaires and debriefing. The couples rated their
      interactions as similar to those at home, suggesting ecological validity, and
      patients with CF experienced the activities as involving more exertion than did
      their partners. The multilevel model results indicated that patients with CF had
      overall lower cortisol levels and flatter slopes across repeated measurements
      than did their significant others. Patients' and significant others' cortisol
      concentrations were significantly associated with each other over time.
      Furthermore, significant others' cortisol was associated with greater
      relationship satisfaction and greater observed rates of patients' illness/pain
      behaviors per minute, but patients' levels of cortisol were not associated with
      relationship variables. This study is the first to examine cortisol in couples
      with CF; the results are discussed in terms of implications for future research.

PMID- 25844496
TI  - Marital status, marital quality, and heart rate variability in the MIDUS cohort.
AB  - Previous research has shown marital status and marital quality are consistent
      predictors of health outcomes, including cardiovascular disease and mortality. To
      better understand the relationship among marital status, marital quality, and
      cardiovascular health, we examined how marital status and marital quality were
      associated with an early indicator of deteriorating cardiovascular health, high
      frequency heart rate variability (HF-HRV). This study uses data from the National
      Survey of Midlife in the United States (MIDUS) Biomarker Substudy (N = 907) to
      examine differences in HF-HRV by traditional marital status categories (married,
      divorced, widowed, and never married) as well as further differentiating between
      the continuously married and remarried. In addition, links were also examined
      between HF-HRV and changes in marital quality (marital satisfaction, support,
      strain) among individuals in long-term marriages. No significant differences in
      HF-HRV were observed between married persons and those widowed, divorced, and
      never married. However, continuously married individuals had higher HF-HRV than
      remarried adults. Increases in marital satisfaction and support over 10 years
      were associated with higher HF-HRV, whereas increased marital strain over 10
      years was associated with lower HF-HRV. Higher HF-HRV among the continuously
      married compared with the remarried suggests that previous marital disruptions
      may have lasting effects on cardiovascular health or that there may be other
      differences between the remarried versus those who remain married to the same
      person. Associations between marital quality and HF-HRV suggest that variations
      in the quality of one's marriage may affect cardiovascular health.

PMID- 25844498
TI  - Self-reports and spouse ratings of neuroticism: perspectives on emotional
      adjustment in couples.
AB  - Evidence of reciprocal associations between individual emotional adjustment and
      the quality of intimate relationships has led to the growing use of interventions
      that combine a focus on couple issues with a focus on individual emotional
      functioning. In these approaches, spouse ratings of emotional functioning can
      provide an important second method of assessment, beyond the much more commonly
      used self-reports. Although an extensive literature demonstrates substantial
      convergent correlations between self-reported and spouse-rated emotional
      adjustment, levels of adjustment evident across these 2 assessment methods are
      much less commonly compared, especially among couples reporting higher levels of
      marital distress. Well-documented limitations of both self-reports and spouse
      ratings suggest that differences--which would not necessarily be evident in
      correlations between methods--might be common and substantial, perhaps raising
      complications in couple assessments and intervention. The present study compared
      self-reports and spouse ratings of neuroticism and its specific components using
      the NEO Personality Inventory-Revised in a sample of 301 middle-aged and older
      couples. For overall neuroticism and the specific facets of anxiety, angry
      hostility, and vulnerability, self-reported levels of negative emotionality were
      consistently lower than the parallel ratings by spouses, most notably among
      couples reporting low levels of marital adjustment. Hence, substantial
      underestimates of negative emotionality obtained through self-reports as compared
      to ratings by spouses (or overestimates as obtained through spouse ratings) may
      be common and could complicate couple assessment and intervention.

PMID- 25844499
TI  - Biomolecule-free, selective detection of o-diphenol and its derivatives with
      WS2/TiO2-based photoelectrochemical platform.
AB  - Herein, a novel photoelectrochemical platform with WS2/TiO2 composites as
      optoelectronic materials was designed for selective detection of o-diphenol and
      its derivatives without any biomolecule auxiliary. First, catechol was chosen as
      a model compound for the discrimination from resorcinol and hydroquinone; then
      several o-diphenol derivatives such as dopamine, caffeic acid, and catechin were
      also detected by employing this proposed photoelectrochemical sensor. Finally,
      the mechanism of such a selective detection has been elaborately explored. The
      excellent selectivity and high sensitivity should be attributed to two aspects:
      (i) chelate effect of adjacent double oxygen atoms in the o-diphenol with the
      Ti(IV) surface site to form a five/six-atom ring structure, which is considered
      as the key point for distinction and selective detection. (ii) This selected
      WS2/TiO2 composites with proper band level between WS2 and TiO2, which could make
      the photogenerated electron and hole easily separated and results in great
      improvement of sensitivity. By employing such a photoelectrochemical platform,
      practical samples including commercial clinic drugs and human urine samples have
      been successfully performed for dopamine detection. This biomolecule-free
      WS2/TiO2 based photoelectrochemical platform demonstrates excellent stability,
      reproducibility, remarkably convenient, and cost-effective advantages, as well as
      low detection limit (e.g., 0.32 MUmol L(-1) for dopamine). It holds great promise
      to be applied for detection of o-diphenol kind species in environment and food
      fields. 

PMID- 25844501
TI  - Bioinspired Tungsten Dithiolene Catalysts for Hydrogen Evolution: A Combined
      Electrochemical, Photochemical, and Computational Study.
AB  - Bis(dithiolene)tungsten complexes, W(VI)O2 (L = dithiolene)2 and W(IV)O (L =
      dithiolene)2, which mimic the active site of formate dehydrogenases, have been
      characterized by cyclic voltammetry and controlled potential electrolysis in
      acetonitrile. They are shown to be able to catalyze the electroreduction of
      protons into hydrogen in acidic organic media, with good Faradaic yields (75-95%)
      and good activity (rate constants of 100 s(-1)), with relatively high
      overpotentials (700 mV). They also catalyze proton reduction into hydrogen upon
      visible light irradiation, in combination with [Ru(bipyridine)3](2+) as a
      photosensitizer and ascorbic acid as a sacrificial electron donor. On the basis
      of detailed DFT calculations, a reaction mechanism is proposed in which the
      starting W(VI)O2 (L = dithiolene)2 complex acts as a precatalyst and hydrogen is
      further formed from a key reduced W-hydroxo-hydride intermediate. 

PMID- 25844500
TI  - Nuclear Magnetic Resonance Structural Mapping Reveals Promiscuous Interactions
      between Clathrin-Box Motif Sequences and the N-Terminal Domain of the Clathrin
      Heavy Chain.
AB  - The recruitment and organization of clathrin at endocytic sites first to form
      coated pits and then clathrin-coated vesicles depend on interactions between the
      clathrin N-terminal domain (TD) and multiple clathrin binding sequences on the
      cargo adaptor and accessory proteins that are concentrated at such sites. Up to
      four distinct protein binding sites have been proposed to be present on the
      clathrin TD, with each site proposed to interact with a distinct clathrin binding
      motif. However, an understanding of how such interactions contribute to clathrin
      coat assembly must take into account observations that any three of these four
      sites on clathrin TD can be mutationally ablated without causing loss of clathrin
      mediated endocytosis. To take an unbiased approach to mapping binding sites for
      clathrin-box motifs on clathrin TD, we used isothermal titration calorimetry
      (ITC) and nuclear magnetic resonance spectroscopy. Our ITC experiments revealed
      that a canonical clathrin-box motif peptide from the AP-2 adaptor binds to
      clathrin TD with a stoichiometry of 3:1. Assignment of 90% of the total visible
      amide resonances in the TROSY-HSQC spectrum of (13)C-, (2)H-, and (15)N-labeled
      TD40 allowed us to map these three binding sites by analyzing the chemical shift
      changes as clathrin-box motif peptides were titrated into clathrin TD. We found
      that three different clathrin-box motif peptides can each simultaneously bind not
      only to the previously characterized clathrin-box site but also to the W-box site
      and the beta-arrestin splice loop site on a single TD. The promiscuity of these
      binding sites can help explain why their mutation does not lead to larger effects
      on clathrin function and suggests a mechanism by which clathrin may be
      transferred between different proteins during the course of an endocytic event. 

PMID- 25844502
TI  - Comparison of Two Different Astragali Radix by a 1H NMR-Based Metabolomic
      Approach.
AB  - Astragali Radix (AR) is a commonly used herbal drug in traditional chinese
      medicine and is widely used for the treatment of diabetes, cardiovascular
      diseases, nephropathy, and neuropathy. The main source of AR in China is the
      dried root of Astragalus membranaceus var. mongholicus (Bge.) Hsiao, and both
      cultivated and wild ARs are used clinically. A systematic comparison of
      cultivated AR (GS-AR) and wild AR (SX-AR) should be performed to ensure the
      clinical efficacy and safety. In this study, the chemical composition of the two
      different ARs, which were collected in the Shanxi (wild) and Gansu (cultivated)
      provinces, were compared by NMR-based metabolic fingerprint coupled with
      multivariate analysis. The SX-AR- and GS-AR-induced metabolic changes in the
      endogenous metabolites in mice were also compared. The results showed that SX-AR
      and GS-AR differed significantly not only in the primary metabolites but also in
      the secondary metabolites. However, alterations among the endogenous metabolites
      in the serum, lung, liver, and spleen were relatively small. This study provided
      a novel and valuable method for the evaluation of the consistency and diversity
      of herbal drugs, and further studies should be conducted on the difference in
      polysaccharides as well as the biological effects between the two kinds of AR. 

PMID- 25844503
TI  - Implementation of a neonatal transcutaneous bilirubin screening programme in
      rural India.
AB  - BACKGROUND: Universal pre-discharge assessment of risk for neonatal
      hyperbilirubinaemia is recommended by the American Academy of Pediatrics. A
      common algorithm is universal transcutaneous bilirubin (TcB) screening, followed
      by confirmatory total serum bilirubin (TSB) testing for results which cause
      concern. There is a paucity of data on the feasibility of TcB screening in low
      income settings. OBJECTIVES: To evaluate the acceptability and feasibility of
      implementing universal TcB screening at a resource-limited hospital in rural
      India, and to determine if it was associated with increased recognition of high
      risk hyperbilirubinaemia. METHODS: In December 2012 at Vivekananda Memorial
      Hospital, Karnataka, India, universal TcB screening at 24-48 hours of life was
      implemented, with TSB estimated if TcB was >75th percentile for age. The
      proportion of families that provided consent and the proportion of infants who
      underwent TcB and TSB testing were calculated. The rates of phototherapy pre- and
      post-implementation and the rate of high-risk hyperbilirubinaemia (TSB >95th
      percentile for age) post-implementation among infants >= 35 weeks gestation were
      determined. RESULTS: Parents of 568 of 660 (86%) eligible infants consented to
      participation. All of these infants were screened with TcB. The proportion who
      had TSB testing was similar in the pre- (6%) and post-implementation (7%)
      periods. The rate of phototherapy was not significantly different after
      implementation (2% vs 3%). Five cases of high-risk hyperbilirubinaemia were
      identified post-implementation. CONCLUSIONS: The study demonstrates the
      acceptability and feasibility of universal TcB screening at a resource-limited
      hospital in rural India. In settings in which early post-discharge follow-up
      cannot be assured, TcB can play a valuable role in identifying infants who need
      evaluation.

PMID- 25844504
TI  - Configurational entropy in thermoset polymers.
AB  - The configurational entropy describes the atomic structure in a material and
      controls several material properties. Often the configurational entropy is
      determined through dielectric or calorimetric measurements where the difference
      between the entropies of the crystalline state and the amorphous state is
      determined. Many amorphous materials such as thermoset polymers have a high
      crystallization barrier, greatly limiting the applicability of the existing
      methods for determining the configurational entropy. In this work, a novel
      differential scanning calorimetry (DSC) method, based on measurement of the glass
      transition temperature at different heating rates, for determination of the
      configurational entropy is introduced. The theory behind the method has a
      universal character for amorphous materials, as it solely involves measurement of
      the glass transition temperature. The temperature dependency of the
      configurational entropy is determined for epoxy resins and PMMA (poly(methyl
      methacrylate)) to demonstrate the versatility of the method. On the basis of the
      findings of the introduced method, the influence of the degree of cross-linking
      and the chemical structure of the network is discussed. 

PMID- 25844505
TI  - Margin Reflex Distance: Differences Based on Camera and Flash Positions.
AB  - PURPOSE: To evaluate the effect of camera flash position on the measurement of
      photographic margin reflex distances (MRD). METHODS: Subjects without any
      ophthalmic disease were prospectively enrolled after institutional review board
      approval. Clinical measurements of MRD1 and interpalpebral fissure were obtained.
      Photographs were then taken with a digital single lens reflex with built-in pop
      up flash (dSLR-pop), a dSLR with lens-mounted ring flash (dSLR-ring), a point-and
      shoot camera, and a smartphone, each in 4 positions: with the camera upright,
      rotated 90 degrees , 180 degrees , and 270 degrees . The images were analyzed
      using ImageJ software to measure MRD1, interpalpebral fissure, horizontal white
      to-white, and distance from nasal limbus to the corneal light reflex. RESULTS:
      Thirty-two eyes of 16 subjects were included (ages 27-65). When using the dSLR
      ring, point-and-shoot, and smartphone, the difference between clinical and
      photographic MRD1 did not reach statistical significance. There was, however, a
      statistically significant difference in the upright position with dSLR-pop (mean
      difference 0.703 mm, sigma = 0.984 mm, p = 0.0008). For dSLR-pop, photographic
      MRD1 in upright versus inverted position differed significantly (mean difference 
      0.562 mm, sigma =0.348 mm, p < 0.0001). Photographic MRD1 between dSLR-pop and
      dSLR-ring showed significant difference in upright position (mean difference 
      0.572 mm, sigma = 0.701 mm, p = 0.0002). There were no statistically significant
      differences between clinical and photographic interpalpebral fissure, and among
      white-to-white and nasal limbus to light reflex measurements in any position in
      all 4 cameras. CONCLUSIONS: When using photographs for measurement of MRD1,
      cameras with a near-coaxial light source and aperture have values that are most
      similar to clinical measurements.

PMID- 25844506
TI  - Efficacy of Intravenous Mannitol in the Management of Orbital Compartment
      Syndrome: A Nonhuman Primate Model.
AB  - PURPOSE: To report the efficacy of intravenous mannitol in the treatment of
      orbital compartment syndrome. METHODS: An experimental study was conducted on 4
      nonhuman primates (8 orbits). Orbital compartment syndrome was simulated by
      injecting autologous blood into both orbits of each nonhuman primate until a
      pressure of 80 mm Hg was reached (time 0). After 10 minutes, nonhuman primates
      were randomized to receive an infusion of either mannitol or saline, given over
      15 minutes. Five minutes after the infusion was complete, lateral canthotomy and
      cantholysis was performed on both orbits in isolated steps every 5 minutes.
      During the study protocol, orbital and intraocular pressures were recorded every
      5 minutes, with a final set of measurements at 60 minutes. The primary outcome
      measures were the mean change in pressure from time 0 to 60 minutes, as well as
      the mean change in pressure during the infusion period. RESULTS: There was no
      statistically significant difference in the mean changes in orbital or
      intraocular pressure from time 0 to 60 minutes of the protocol. However, during
      the infusion period there was significantly greater decrease in both orbital and
      intraocular pressure in the mannitol compared with saline group (-34.0 vs. -9.3
      mm Hg for orbital pressure [p = 0.03]; -34.8 vs. -9.7 mm Hg for intraocular
      pressure [p = 0.04]). CONCLUSIONS: While the definitive treatment of orbital
      compartment syndrome is lateral canthotomy and cantholysis, mannitol results in a
      rapid and clinically meaningful drop in orbital and intraocular pressure. The
      authors believe that their data support the routine use of mannitol in orbital
      compartment syndrome, especially when there is a delay in timely surgical
      management.

PMID- 25844507
TI  - Maxillary anterior alignment stability in Class I and Class II malocclusions
      treated with or without extraction.
AB  - OBJECTIVE: To compare the postretention stability of maxillary incisors alignment
      in subjects with Class I and II malocclusion treated with or without extractions.
      MATERIALS AND METHODS: The sample comprised 103 subjects with initial maxillary
      anterior irregularity greater than 3 mm and was divided into four groups: group 1
      comprised 19 patients with Class I malocclusion treated with nonextraction (mean
      initial age = 13.06 years); group 2 comprised 19 patients with Class II
      malocclusion treated with nonextraction (mean initial age = 12.54 years); group 3
      comprised 30 patients with Class I malocclusion treated with extractions (mean
      initial age = 13.16 years); group 4 comprised 35 patients with Class II
      malocclusion treated with extractions (mean initial age = 12.99 years). Dental
      casts were obtained at three different stages: pretreatment (T1), posttreatment
      (T2), and long-term posttreatment (T3). Maxillary incisor irregularity and arch
      dimensions were evaluated. Intergroup comparisons were performed by one-way
      analysis of variance followed by Tukey tests. RESULTS: In the long-term
      posttreatment period, relapse of maxillary crowding and arch dimensions was
      similar in all groups. CONCLUSION: Changes in maxillary anterior alignment in
      Class I and Class II malocclusions treated with nonextractions and with
      extractions were similar in the long-term posttreatment period.

PMID- 25844508
TI  - Compression and hypoxia play independent roles while having combinative effects
      in the osteoclastogenesis induced by periodontal ligament cells.
AB  - OBJECTIVE: To investigate the isolated and combined effects of compression and
      hypoxia on the osteoclastogenesis induced by periodontal ligament cells (PDLCs).
      MATERIALS AND METHODS: A periodontal ligament tissue model (PDLtm) was
      established by 3-D culturing human PDLCs on a thin sheet of poly lactic-co
      glycolic acid scaffold. The PDLtm was treated with hypoxia and/or compression for
      6, 24, or 72 hours. After that, a real-time polymerase chain reaction was used
      for gene expression analysis. The conditioned media were used for the coculture
      of osteoblast and osteoclast (OC) precursors; tartrate-resistant acid phosphatase
      staining was done to examine OC formation. RESULTS: Either compression or hypoxia
      alone significantly up-regulated the gene expression of pro-osteoclastogenic
      cytokines in the PDLtm and enhanced osteoclastogenesis in the cocultures, and the
      combination of the two had significantly stronger effects than either stimulation
      alone. In addition, comparing the two stimulants, we found that the
      osteoclastogenic property of the PDLCs peaked earlier (at 6 hours) in the
      compression group than in the hypoxia group (at 24 hours). CONCLUSIONS: Both
      compressive force and hypoxia may take part in initiating osteoclastogenesis in
      orthodontic tooth movement and may have combinatory effects, which could update
      our concepts of the mechanisms involved in the initiation of bone resorption on
      the pressure side of the tooth in question.

PMID- 25844510
TI  - Lower extremity revascularization in nursing home residents: surgery as
      palliation.

PMID- 25844509
TI  - Objective, comparative assessment of the penetration depth of temporal-focusing
      microscopy for imaging various organs.

PMID- 25844511
TI  - In the Aftermath of the National Children's Study.

PMID- 25844513
TI  - When domestic goes capital: Juror decision making in capital murder trials
      involving domestic homicide.
AB  - Prior research suggests that homicide cases involving familial offenders and
      victims are subject to a "domestic discount" that reduces sentencing severity.
      However, the operation of a domestic discount in regard to death penalty
      sentencing has been rarely examined. The current research uses a near-population
      of jury decisions in capital murder trials conducted in North Carolina from 1991
      to 2009 (n = 800), and a series of logistic regression analyses to determine
      whether there is (a) a direct effect between offender-victim relationship (e.g.,
      domestic, friend/acquaintance, and stranger) and jury decision making, and/or (b)
      whether domestic offender-victim relationship (as well as other offender-victim
      relationships) moderates the effect of legal and extralegal case characteristics
      on jury assessment of the death penalty. Our findings revealed no empirical
      support for a "domestic discount" whereby juries are less likely to impose death
      sentences in cases involving domestic homicides. However, substantial differences
      in predictors of death sentencing were found across offender-victim dyads; most
      notably, domestic homicide cases demonstrated the most legalistic model of jury
      decisions to impose death sentences.

PMID- 25844512
TI  - Oxidovanadium(IV/V) complexes as new redox mediators in dye-sensitized solar
      cells: a combined experimental and theoretical study.
AB  - Corrosiveness is one of the main drawbacks of using the iodide/triiodide redox
      couple in dye-sensitized solar cells (DSSCs). Alternative redox couples including
      transition metal complexes have been investigated where surprisingly high
      efficiencies for the conversion of solar to electrical energy have been achieved.
      In this paper, we examined the development of a DSSC using an electrolyte based
      on square pyramidal oxidovanadium(IV/V) complexes. The oxidovanadium(IV) complex
      (Ph4P)2[V(IV)O(hybeb)] was combined with its oxidized analogue
      (Ph4P)[V(V)O(hybeb)] {where hybeb(4-) is the tetradentate diamidodiphenolate
      ligand [1-(2-hydroxybenzamido)-2-(2-pyridinecarboxamido)benzenato}and applied as
      a redox couple in the electrolyte of DSSCs. The complexes exhibit large electron
      exchange and transfer rates, which are evident from electron paramagnetic
      resonance spectroscopy and electrochemistry, rendering the oxidovanadium(IV/V)
      compounds suitable for redox mediators in DSSCs. The very large self-exchange
      rate constant offered an insight into the mechanism of the exchange reaction most
      likely mediated through an outer-sphere exchange mechanism. The [V(IV)O(hybeb)](2
      )/[V(V)O(hybeb)](-) redox potential and the energy of highest occupied molecular
      orbital (HOMO) of the sensitizing dye N719 and the HOMO of [V(IV)O(hybeb)](2-)
      were calculated by means of density functional theory electronic structure
      calculation methods. The complexes were applied as a new redox mediator in DSSCs,
      while the cell performance was studied in terms of the concentration of the
      reduced and oxidized form of the complexes. These studies were performed with the
      commercial Ru-based sensitizer N719 absorbed on a TiO2 semiconducting film in the
      DSSC. Maximum energy conversion efficiencies of 2% at simulated solar light (AM
      1.5; 1000 W m(-2)) with an open circuit voltage of 660 mV, a short-circuit
      current of 5.2 mA cm(-2), and a fill factor of 0.58 were recorded without the
      presence of any additives in the electrolyte. 

PMID- 25844514
TI  - Predicting recidivism among adult male child pornography offenders: Development
      of the Child Pornography Offender Risk Tool (CPORT).
AB  - In this study, we developed a structured risk checklist, the Child Pornography
      Offender Risk Tool (CPORT), to predict any sexual recidivism among adult male
      offenders with a conviction for child pornography offenses. We identified
      predictors of sexual recidivism using a 5-year fixed follow-up analysis from a
      police case file sample of 266 adult male child pornography offenders in the
      community after their index offense. In our 5-year follow-up, 29% committed a new
      offense, and 11% committed a new sexual offense, with 3% committing a new contact
      sexual offense against a child and 9% committing a new child pornography offense.
      The CPORT items comprised younger offender age, any prior criminal history, any
      contact sexual offending, any failure on conditional release, indication of
      sexual interest in child pornography material or prepubescent or pubescent
      children, more boy than girl content in child pornography, and more boy than girl
      content in other child depictions. The CPORT was significantly associated with
      any sexual recidivism, with moderate predictive accuracy, and thus has promise in
      the risk assessment of adult male child pornography offenders with further cross
      validation.

PMID- 25844515
TI  - Effects of victim presence and coercion in restorative justice: An experimental
      paradigm.
AB  - There is little experimental work examining the ways in which particular
      procedural features of restorative justice impact offenders. This research
      describes a new experimental paradigm designed to advance knowledge about causal
      relationships in restorative justice settings. Apologizing is a core component of
      restorative procedures, and can result in beneficial outcomes, but previous
      research suggests that coercion to apologize and the absence of victims in
      restorative procedures may negatively impact these outcomes. The experimental
      procedure elicited confessions and apologies for a transgression from
      participants (N = 101) in a deceptive paradigm. We manipulated coercion (coerced,
      not coerced) and victim presence (direct, surrogate, ambiguous) to test their
      effects on offenders' subjective experiences of offering an apology, as well as
      their effects on the quality of offenders' apologies. Findings indicated that the
      victim presence and coercion manipulations significantly impacted some of the
      subjective perceptions of apologizers, including perceptions of accountability
      and transgression finality. In addition, independent raters evaluated the degree
      to which the transgressor's apologies conveyed remorse, acceptance of guilt, and
      potential for dispute resolution. Victim presence and coercion consistently
      affected the ability of transgressors to convey high quality apologies.
      Implications for future research and restorative procedures are discussed.

PMID- 25844516
TI  - Using reality monitoring to improve deception detection in the context of the
      cognitive interview for suspects.
AB  - Research has found that deception detection accuracy in the context of suspect
      interrogation hovers around chance levels. Geiselman (2012) adapted the cognitive
      interview (typically used for witnesses) for use with suspects (CIS) and found
      that judgments of deception were more accurate than previous interrogation
      techniques. The current study attempted to use the CIS to improve deception
      detection with Reality Monitoring (RM: Vrij et al., 2008), which has already been
      validated in the context of witness statements. One hundred sixty-six
      undergraduate students were randomly assigned to 2 conditions. In the Truthful
      condition, participants played a game with a confederate, whereas in the
      Deceptive condition, participants rehearsed (but did not experience) a synopsis
      of the game scenario. Participants in the Deceptive condition were also
      instructed to steal $10 from a confederate's wallet. In both conditions, $10 was
      purported to be missing and a researcher blind to condition conducted a CIS.
      Statement veracity was coded using 6 of the RM criteria advanced by Vrij et al.
      (frequency of visual, auditory, spatial, temporal, cognitive, and affective
      details). According to results from a MANOVA, truthful and deceptive statements
      differed significantly on all RM criteria, with the exception of affective
      details, validating the importance for evaluation of statement veracity (p <=
      .01). Further, a binary logistic regression found that combining the RM criteria
      together correctly classified 86.6% of statements, chi(2)(6) = 114.4, p < .001,
      with excellent sensitivity and specificity (.899 and .833, respectively). As
      well, Visual, Auditory, and Cognitive details uniquely predicted condition.
      Findings support using RM criteria to detect deception in interviews conducted
      with the CIS.

PMID- 25844517
TI  - Interviewing strategically to elicit admissions from guilty suspects.
AB  - In this article we introduce a novel interviewing tactic to elicit admissions
      from guilty suspects. By influencing the suspects' perception of the amount of
      evidence the interviewer holds against them, we aimed to shift the suspects'
      counterinterrogation strategies from less to more forthcoming. The proposed
      tactic (SUE-Confrontation) is a development of the Strategic Use of Evidence
      (SUE) framework and aims to affect the suspects' perception by confronting them
      with statement-evidence inconsistencies. Participants (N = 90) were asked to
      perform several mock criminal tasks before being interviewed using 1 of 3
      interview techniques: (a) SUE-Confrontation, (b) Early Disclosure of Evidence, or
      (c) No Disclosure of Evidence. As predicted, the SUE-Confrontation interview
      generated more statement-evidence inconsistencies from suspects than the Early
      Disclosure interview. Importantly, suspects in the SUE-Confrontation condition
      (vs. Early and No disclosure conditions) admitted more self-incriminating
      information and also perceived the interviewer to have had more information about
      the critical phase of the crime (the phase where the interviewer lacked
      evidence). The findings show the adaptability of the SUE-technique and how it may
      be used as a tool for eliciting admissions.

PMID- 25844519
TI  - Use of smartphone cameras for simplified and cost-effective video recording of
      microvascular techniques.

PMID- 25844520
TI  - Severe traumatic facial injury: avatars and thermographic damage evaluation.

PMID- 25844521
TI  - Reply: Modified Transconjunctival Lower Lid Approach for Orbital Fractures in
      East Asian Patients: The Lateral Paracanthal Incision Revisited.

PMID- 25844522
TI  - Ultrafast imaging of surface plasmons propagating on a gold surface.
AB  - We record time-resolved nonlinear photoemission electron microscopy (tr-PEEM)
      images of propagating surface plasmons (PSPs) launched from a lithographically
      patterned rectangular trench on a flat gold surface. Our tr-PEEM scheme involves
      a pair of identical, spatially separated, and interferometrically locked
      femtosecond laser pulses. Power-dependent PEEM images provide experimental
      evidence for a sequential coherent nonlinear photoemission process, in which one
      laser source launches a PSP through a linear interaction, and the second
      subsequently probes the PSP via two-photon photoemission. The recorded time
      resolved movies of a PSP allow us to directly measure various properties of the
      surface-bound wave packet, including its carrier wavelength (783 nm) and group
      velocity (0.95c). In addition, tr-PEEM images reveal that the launched PSP may be
      detected at least 250 MUm away from the coupling trench structure. 

PMID- 25844518
TI  - Nanoscale strategies: treatment for peripheral vascular disease and critical limb
      ischemia.
AB  - Peripheral vascular disease (PVD) is one of the most prevalent vascular diseases
      in the U.S. afflicting an estimated 8 million people. Obstruction of peripheral
      arteries leads to insufficient nutrients and oxygen supply to extremities, which,
      if not treated properly, can potentially give rise to a severe condition called
      critical limb ischemia (CLI). CLI is associated with extremely high morbidities
      and mortalities. Conventional treatments such as angioplasty, atherectomy, stent
      implantation and bypass surgery have achieved some success in treating localized
      macrovascular disease but are limited by their invasiveness. An emerging
      alternative is the use of growth factor (delivered as genes or proteins) and cell
      therapy for PVD treatment. By delivering growth factors or cells to the ischemic
      tissue, one can stimulate the regeneration of functional vasculature network
      locally, re-perfuse the ischemic tissue, and thus salvage the limb. Here we
      review recent advance in nanomaterials, and discuss how their application can
      improve and facilitate growth factor or cell therapies. Specifically,
      nanoparticles (NPs) can serve as drug carrier and target to ischemic tissues and
      achieve localized and sustained release of pro-angiogenic proteins. As nonviral
      vectors, NPs can greatly enhance the transfection of target cells with pro
      angiogenic genes with relatively fewer safety concern. Further, NPs may also be
      used in combination with cell therapy to enhance cell retention, cell survival
      and secretion of angiogenic factors. Lastly, nano/micro fibrous vascular grafts
      can be engineered to better mimic the structure and composition of native
      vessels, and hopefully overcome many complications/limitations associated with
      conventional synthetic grafts. 

PMID- 25844524
TI  - Nine new phosphorene polymorphs with non-honeycomb structures: a much extended
      family.
AB  - We predict a new class of monolayer phosphorus allotropes, namely, epsilon-P,
      zeta-P, eta-P, and theta-P. Distinctly different from the monolayer alpha-P
      (black) and previously predicted beta-P (Phys. Rev. Lett. 2014, 112, 176802),
      gamma-P, and delta-P (Phys. Rev. Lett. 2014, 113, 046804) with buckled honeycomb
      lattice, the new allotropes are composed of P4 square or P5 pentagon units that
      favor tricoordination for P atoms. The new four polymorphs, together with five
      additional hybrid polymorphs, greatly enrich the phosphorene structures, and
      their stabilities are confirmed by first-principles calculations. In particular,
      the theta-P is shown to be equally stable as the alpha-P (black) and more stable
      than all previously reported phosphorene polymorphs. Prediction of nonvolatile
      ferroelastic switching and structural transformation among different polymorphs
      under strains points out their potential applications via strain engineering. 

PMID- 25844523
TI  - Functional outcomes after lower extremity revascularization in nursing home
      residents: a national cohort study.
AB  - IMPORTANCE: Lower extremity revascularization often seeks to allow patients with
      peripheral arterial disease to maintain the ability to walk, a key aspect of
      functional independence. Surgical outcomes in patients with high levels of
      functional dependence are poorly understood. OBJECTIVE: To determine functional
      status trajectories, changes in ambulatory status, and survival after lower
      extremity revascularization in nursing home residents. DESIGN: Using full
      Medicare claims data for 2005 to 2009, we identified nursing home residents who
      underwent lower extremity revascularization. With the Minimum Data Set for
      Nursing Homes activities of daily living summary score, we examined changes in
      their ambulatory and functional status after surgery. We identified patient and
      surgery characteristics associated with a composite measure of clinical and
      functional failure-death or nonambulatory status 1 year after surgery. SETTING:
      All nursing homes in the United States participating in Medicare or Medicaid.
      PARTICIPANTS: Nursing home residents who underwent lower extremity
      revascularization. MAIN OUTCOMES AND MEASURES: Functional status, ambulatory
      status, and death. RESULTS: During the study period, 10,784 long-term nursing
      home residents underwent lower extremity revascularization. Prior to surgery, 75%
      of the residents were not walking; 40% had experienced functional decline. One
      year after surgery, 51% of patients had died, 28% were nonambulatory, and 32% had
      sustained functional decline. Among 1672 residents who were ambulatory before
      surgery, 63% had died or were nonambulatory at 1 year; among 7188 who were
      nonambulatory, 89% had died or were nonambulatory. After multivariate adjustment,
      factors independently associated with death or nonambulatory status were 80 years
      or older (adjusted hazard ratio [AHR], 1.28; 95% CI, 1.16-1.40), cognitive
      impairment (AHR, 1.23; 95% CI, 1.18-1.29), congestive heart failure (AHR, 1.16;
      95% CI, 1.11-1.22), renal failure (AHR, 1.09; 95% CI, 1.04-1.14), emergent
      surgery (AHR, 1.29; 95% CI, 1.23-1.35), nonambulatory status before surgery (AHR,
      1.88; 95% CI, 1.78-1.99), and decline in activities of daily living before
      surgery (AHR, 1.23; 95% CI, 1.18-1.28). CONCLUSIONS AND RELEVANCE: Of nursing
      home residents in the United States who undergo lower extremity
      revascularization, few are alive and ambulatory 1 year after surgery. Most who
      were still alive had gained little, if any, function.

PMID- 25844525
TI  - Untangling the etiology of ascites.
AB  - BACKGROUND: Amyloidosis is a systemic disease known to affect a vast range of
      organs, including the liver, heart, and kidney. When infiltrating the liver,
      amyloidosis typically does not present with cirrhosis. Typical presentation
      includes hepatomegaly with some mild laboratory abnormalities. CASE REPORT: A 72
      year-old man presented with a 2-week history of worsening abdominal, scrotal, and
      extremity swelling. He endorsed melanotic stools and intermittent dizziness with
      a 10-pound weight gain. Vitals revealed a blood pressure of 82/57 mmHg and a
      pulse of 83 beats/min with positive orthostatic changes. Mild bibasilar crackles
      were noted. His abdomen was moderately distended with a fluid wave present, but
      no hepatosplenomegaly was noted. He displayed anasarca with significant extremity
      and scrotal edema, but no jaundice, telangiectasias, or other stigmata of chronic
      liver disease were present. Liver function tests demonstrated a total bilirubin
      of 1.5 mg/dL (normal value: 0.2-1.2 mg/dL), AST 111 IU/L (normal value 5-34
      IU/L), ALT 51 IU/L (normal value 5-55 IU/L), and GGT 583 U/L (12-64 U/L).
      Alkaline phosphatase was 645 U/L (40-150 U/L). Analysis of peritoneal fluid was
      consistent with portal hypertension due to liver disease. Given an atypical
      presentation of cirrhosis with unclear etiology, a biopsy was performed and
      revealed amyloid deposition. CONCLUSIONS: Liver disease can be due to various
      etiologies, many of which can present ambiguously. Although the most typical
      etiologies have been well defined, we present a case of an atypical presentation
      of hepatic amyloidosis discovered in a patient with ascites and without typical
      hepatomegaly.

PMID- 25844526
TI  - Preference for cute infants does not depend on their ethnicity or species:
      evidence from hypothetical adoption and donation paradigms.
AB  - Results of previous work suggest a preference of adult observers for cute
      compared to less cute infants. In Study 1 we investigated whether the preference
      for cute infants depends on the ethnicity and species of the infant. We
      simultaneously presented two faces (one cute and one less cute) and asked
      Caucasian participants to choose the infant to whom they would rather give a toy
      (Task 1) and which infant they would rather adopt (Task 2). The infants were
      Caucasian or African human babies or dog puppies. For all face categories and in
      both tasks we found a strong preference for cute infants. A possible reason for
      preferring cute infants may be that cute infants look healthier than less cute
      infants. To investigate whether cuteness is associated with the assessment of
      health we conducted Study 2. Faces of Caucasian and African infants and dog
      puppies were rated for cuteness and health. The findings revealed a significant
      relationship between health and cuteness evaluation across all stimuli. We
      suggest that one reason why cute infants are preferred might be because they are
      perceived as being healthier. 

PMID- 25844527
TI  - Practice Guidance for Buprenorphine for the Treatment of Opioid Use Disorders:
      Results of an Expert Panel Process.
AB  - BACKGROUND: Although the number of physicians credentialed to prescribe
      buprenorphine has increased over time, many credentialed physicians may be
      reluctant to treat individuals with opioid use disorders due to discomfort with
      prescribing buprenorphine. Although prescribing physicians are required to
      complete a training course, many have questions about buprenorphine and treatment
      guidelines have not been updated to reflect clinical experience in recent years.
      We report on an expert panel process to update and expand buprenorphine
      guidelines. METHODS: We identified candidate guidelines through expert opinion
      and a review of the literature and used a modified RAND/UCLA Appropriateness
      Method to assess the validity of the candidate guidelines. An expert panel
      completed 2 rounds of rating, with a meeting to discuss the guidelines between
      the first and second ratings. RESULTS: Through the rating process, expert panel
      members rated 90 candidate guideline statements across 8 domains, including
      candidacy for buprenorphine treatment, dosing of buprenorphine, psychosocial
      counseling, and treatment of co-occurring depression and anxiety. A total of 65
      guideline statements (72%) were rated as valid. Expert panel members had
      agreement in some areas, such as the treatment of co-occurring mental health
      problems, but disagreement in others, including the appropriate dosing of
      buprenorphine given patient complexities. CONCLUSIONS: Through an expert panel
      process, we developed an updated and expanded set of buprenorphine treatment
      guidelines; this additional guidance may increase credentialed physicians'
      comfort with prescribing buprenorphine to patients with opioid use disorders.
      Future efforts should focus on appropriate dosing guidance and ensuring that
      guidelines can be adapted to a variety of practice settings.

PMID- 25844528
TI  - Substrate-Controlled Stereochemistry in Natural Product Biosynthesis.
AB  - Enzymes are generally believed to be highly regio- and stereoselective catalysts
      that strictly control the reaction coordinates and dominate the final catalytic
      outcomes. However, recent studies have started to suggest that substrates
      sometimes play key roles in determining the product selectivity in enzyme
      catalysis. Here, we highlight several enzymatic reactions in which the
      stereoselectivity is, at least in large part, governed by the intrinsic
      properties of the substrate rather than by characteristics of the enzyme. These
      reactions are involved in the biosynthesis of different classes of natural
      products, including lanthipeptides, sactipeptides, and polyketides. Understanding
      the mechanism of substrate-controlled stereospecificity may not only expand our
      knowledge of enzyme catalysis and enzyme evolution but also guide bioengineering
      efforts to produce novel valuable products. 

PMID- 25844529
TI  - TLR9 2848 GA heterozygotic status possibly predisposes fetuses and newborns to
      congenital infection with human cytomegalovirus.
AB  - BACKGROUND: Some single nucleotide polymorphisms (SNP), located in Toll-like
      receptor (TLR) genes, were reported to be associated with human cytomegalovirus
      (HCMV) infections. The study was aimed to assess the correlation of SNPs at TLR4
      and TLR9 genes with the occurrence of congenital cytomegaly, based on available
      samples. METHODS: Reported case-control study included both HCMV infected and non
      infected fetuses and newborns. The specimens were classified to the molecular
      analyses, based on serological features of the recent infection and HCMV DNAemia
      in body fluids. TLR SNPs were studied, using multiplex nested PCR-RFLP assay, and
      determined genotypes were confirmed by sequencing. Hardy-Weinberg equilibrium was
      assessed for the identified genotypes. The linkage disequilibrium was also
      estimated for TLR4 SNPs. A relationship between the status of TLR genotypes and
      congenital cytomegaly development was estimated, using a logistic regression
      model. RESULTS: Hardy Weinberg equilibrium was observed for almost all SNPs, both
      infected and non-infected patients, with exception of TLR4 896 A>G polymorphism
      in the control group (P<=0.050). TLR4 896 A>G and 1196 C>T SNPs were found in
      linkage disequilibrium in both study groups (P<=0.050). The CC genotype at TLR4
      1196 SNP and the GA variant at TLR9 2848 G>A SNP were significantly associated
      with HCMV infection (P<=0.050). The risk of congenital cytomegaly was higher in
      heterozygotes at TLR9 SNP than in the carriers of other genotypic variants at the
      reported locus (OR 4.81; P<=0.050). The GC haplotype at TLR4 SNPs and GCA
      variants at TLR4 and TLR9 SNPs were significantly associated with HCMV infection
      (P<=0.0001). The ACA variants were more frequent among fetuses and neonates with
      symptomatic, rather than asymptomatic cytomegaly (P<=0.0001). CONCLUSIONS: TLR4
      and TLR9 polymorphisms may contribute to the development of congenital infection
      with HCMV in fetuses and neonates. The TLR9 2848 GA heterozygotic status possibly
      predisposes to HCMV infection, increasing the risk of congenital cytomegaly
      development.

PMID- 25844530
TI  - Endurance training alters basal erythrocyte MCT-1 contents and affects the
      lactate distribution between plasma and red blood cells in T2DM men following
      maximal exercise.
AB  - Chronic elevated lactate levels are associated with insulin resistance in
      patients with type 2 diabetes mellitus (T2DM). Furthermore, lactacidosis plays a
      role in limiting physical performance. Erythrocytes, which take up lactate via
      monocarboxylate transporter (MCT) proteins, may help transport lactate within the
      blood from lactate-producing to lactate-consuming organs. This study investigates
      whether cycling endurance training (3 times/week for 3 months) alters the basal
      erythrocyte content of MCT-1, and whether it affects lactate distribution
      kinetics in the blood of T2DM men (n = 10, years = 61 +/- 9, body mass index = 31
      +/- 3 kg/m(2)) following maximal exercise (WHO step-incremental cycle ergometer
      test). Immunohistochemical staining indicated that basal erythrocyte contents of
      MCT-1 protein were up-regulated (+90%, P = 0.011) post-training. Erythrocyte and
      plasma lactate increased from before acute exercise (= resting values) to
      physical exhaustion pre- as well as post-training (pre-training: +309%, P =
      0.004; +360%, P < 0.001; post-training: +318%, P = 0.008; +300%, P < 0.001), and
      did not significantly decrease during 5 min recovery. The lactate ratio
      (erythrocytes:plasma) remained unchanged after acute exercise pre-training, but
      was significantly increased after 5 min recovery post-training (compared with the
      resting value) (+22%, P = 0.022). The results suggest an increased time-delayed
      influx of lactate into erythrocytes following an acute bout of exercise in
      endurance-trained diabetic men. 

PMID- 25844532
TI  - Using estimated factor scores from a bifactor analysis to examine the unique
      effects of the latent variables measured by the WAIS-IV on academic achievement.
AB  - This study used estimated factor scores from a bifactor analysis of the Wechsler
      Adult Intelligence Scale-Fourth Edition (WAIS-IV) to examine the unique effects
      of its latent variables on academic achievement. In doing so, we addressed the
      potential limitation of multicollinearity in previous studies of the incremental
      validity of the WAIS-IV. First, factor scores representing psychometric g and 4
      group factors representing the WAIS-IV index scales were computed from a bifactor
      model. Subtest and composite scores for the Wechsler Individual Achievement Test
      Third Edition (WIAT-II) were then predicted from these estimated factor scores in
      simultaneous multiple regression. Results of this study only partially replicated
      the findings of previous research on the incremental validity of scores that can
      be derived from performance on the WAIS-IV. Although we found that psychometric g
      is the most important underlying construct measured by the WAIS-IV for the
      prediction of academic achievement in general, results indicated that the unique
      effect of Verbal Comprehension is also important for predicting achievement in
      reading, spelling, and oral communication skills. Based on these results,
      measures of both psychometric g and Verbal Comprehension could be cautiously
      interpreted when considering high school students' performance in these areas of
      achievement.

PMID- 25844531
TI  - Intrinsic patterns of coupling between correlation and amplitude of low-frequency
      fMRI fluctuations are disrupted in degenerative dementia mainly due to functional
      disconnection.
AB  - Low frequency fluctuations (LFFs) of the BOLD signal are a major discovery in the
      study of the resting brain with functional magnetic resonance imaging (fMRI). Two
      fMRI-based measures, functional connectivity (FC), a measure of signal
      synchronicity, and the amplitude of LFFs (ALFF), a measure of signal periodicity,
      have been proved to be sensitive to changes induced by several neurological
      diseases, including degenerative dementia. In spite of the increasing use of
      these measures, whether and how they are related to each other remains to be
      elucidated. In this work we used voxel-wise FC and ALFF computed in different
      frequency bands (slow-5: 0.01-0.027 Hz; slow-4: 0.027-0.073 Hz; and full-band:
      0.01-0.073 Hz), in order to assess their relationship in healthy elderly as well
      as the relevant changes induced by Alzheimer's Disease (AD) and Mild Cognitive
      Impairment (MCI). We found that in healthy elderly subjects FC and ALFF are
      positively correlated in anterior and posterior cingulate cortex (full-band, slow
      4 and slow-5), temporal cortex (full-band and slow-5), and in a set of
      subcortical regions (full-band and slow-4). These correlation patterns between FC
      and ALFF were absent in either AD or MCI patients. Notably, the loss of
      correlation between FC and ALFF in the AD group was primarily due to changes in
      FC rather than in ALFF. Our results indicate that degenerative dementia is
      characterized by a loss of global connection rather than by a decrease of
      fluctuation amplitude. 

PMID- 25844533
TI  - Development and initial validation of the Child Disgust Scale.
AB  - Although disgust sensitivity (DS) has been implicated in the development of
      anxiety disorders in children, the absence of a measure of DS specifically for
      children has not allowed for an adequate test of this claim. To fill this
      important gap in the literature, this investigation presents a series of studies
      on the development and examination of the psychometric properties (including
      reliability, validity, and factor structure) of scores on a newly developed Child
      Disgust Scale (CDS). Exploratory factor analysis in Study 1 (N = 1,500) found
      that a bifactor model, which allows for a "g" DS factor in addition to 2 distinct
      factors of Disgust Avoidance and Disgust Affect, was the best fit for the data.
      Study 2 (N = 573) confirmed a two-factor bifactor model above and beyond a 1
      factor model that controlled for method effects due to reverse-worded items.
      Results from Study 3 (N = 50) provided support for convergent and discriminant
      validity such that scores on the CDS were significantly correlated with measures
      of anxiety and fear, but not depression. Finally, Study 4 (N = 86) found that the
      CDS differentiated children with a diagnosis of specific phobia (n = 43) from a
      matched nonclinical community sample of children (n = 43), such that those with a
      specific phobia reported greater DS compared with controls. Results from these
      studies suggest that the CDS is a developmentally appropriate measure with good
      psychometric properties that can aid research on the role of disgust sensitivity
      in anxiety-related disorders in children.

PMID- 25844535
TI  - Electrokinetic control of bacterial deposition and transport.
AB  - Microbial biofilms can cause severe problems in technical installations where
      they may give rise to microbially influenced corrosion and clogging of filters
      and membranes or even threaten human health, e.g. when they infest water
      treatment processes. There is, hence, high interest in methods to prevent
      microbial adhesion as the initial step of biofilm formation. In environmental
      technology it might be desired to enhance bacterial transport through porous
      matrices. This motivated us to test the hypothesis that the attractive
      interaction energy allowing cells to adhere can be counteracted and overcome by
      the shear force induced by electroosmotic flow (EOF, i.e. the water flow over
      surfaces exposed to a weak direct current (DC) electric field). Applying EOF of
      varying strengths we quantified the deposition of Pseudomonas fluorescens Lp6a in
      columns containing glass collectors and on a quartz crystal microbalance. We
      found that the presence of DC reduced the efficiency of initial adhesion and
      bacterial surface coverage by >85%. A model is presented which quantitatively
      explains the reduction of bacterial adhesion based on the extended Derjaguin,
      Landau, Verwey, and Overbeek (XDLVO) theory of colloid stability and the EOF
      induced shear forces acting on a bacterium. We propose that DC fields may be used
      to electrokinetically regulate the interaction of bacteria with surfaces in order
      to delay initial adhesion and biofilm formation in technical installations or to
      enhance bacterial transport in environmental matrices. 

PMID- 25844534
TI  - Testing whether the DSM-5 personality disorder trait model can be measured with a
      reduced set of items: An item response theory investigation of the Personality
      Inventory for DSM-5.
AB  - The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders
      (DSM-5) includes an alternative model of personality disorders (PDs) in Section
      III, consisting in part of a pathological personality trait model. To date, the
      220-item Personality Inventory for DSM-5 (PID-5; Krueger, Derringer, Markon,
      Watson, & Skodol, 2012) is the only extant self-report instrument explicitly
      developed to measure this pathological trait model. The present study used item
      response theory-based analyses in a large sample (n = 1,417) to investigate
      whether a reduced set of 100 items could be identified from the PID-5 that could
      measure the 25 traits and 5 domains. This reduced set of PID-5 items was then
      tested in a community sample of adults currently receiving psychological
      treatment (n = 109). Across a wide range of criterion variables including NEO PI
      R domains and facets, DSM-5 Section II PD scores, and externalizing and
      internalizing outcomes, the correlational profiles of the original and reduced
      versions of the PID-5 were nearly identical (rICC = .995). These results provide
      strong support for the hypothesis that an abbreviated set of PID-5 items can be
      used to reliably, validly, and efficiently assess these personality disorder
      traits. The ability to assess the DSM-5 Section III traits using only 100 items
      has important implications in that it suggests these traits could still be
      measured in settings in which assessment-related resources (e.g., time,
      compensation) are limited.

PMID- 25844536
TI  - Wastewater analysis to monitor spatial and temporal patterns of use of two
      synthetic recreational drugs, ketamine and mephedrone, in Italy.
AB  - Wastewater analysis was applied in a four-year monitoring study to assess
      temporal and spatial patterns of ketamine and mephedrone use in the general
      population in Italy. Composite raw wastewater samples were collected from sewage
      treatment plants (STPs) in 17 cities. Target analytes were measured using a
      validated method based on solid phase extraction and liquid chromatography
      coupled to tandem mass spectrometry analysis. Mass loads were use to assess
      ketamine and mephedrone use and were normalized to the population served by the
      plants. Ketamine was detected in wastewater in all except one (Palermo) of the
      cities investigated, while mephedrone was detected only in Bologna and Florence.
      Ketamine mass loads progressively increased from 2010 to 2013, and in Milan rose
      from 1 to 1.5 g/day in 2008-2010 to 3.4-3.6 g/day in 2013-2014. Mass loads were
      higher in north and central Italy than in the south, and in larger rather than
      small cities. Wastewater analysis was suitable to provide objective and up-to
      date information on the use of ketamine in Italy, to identify ketamine spatial
      and temporal changes, and to confirm the low use of mephedrone. These results can
      complement information from population surveys which often provide only scant and
      incomplete figures for these substances. 

PMID- 25844537
TI  - Hybridized electromagnetic-triboelectric nanogenerator for scavenging air-flow
      energy to sustainably power temperature sensors.
AB  - We report a hybridized nanogenerator with dimensions of 6.7 cm * 4.5 cm * 2 cm
      and a weight of 42.3 g that consists of two triboelectric nanogenerators (TENGs)
      and two electromagnetic generators (EMGs) for scavenging air-flow energy. Under
      an air-flow speed of about 18 m/s, the hybridized nanogenerator can deliver
      largest output powers of 3.5 mW for one TENG (in correspondence of power per unit
      mass/volume: 8.8 mW/g and 14.6 kW/m(3)) at a loading resistance of 3 MOmega and
      1.8 mW for one EMG (in correspondence of power per unit mass/volume: 0.3 mW/g and
      0.4 kW/m(3)) at a loading resistance of 2 kOmega, respectively. The hybridized
      nanogenerator can be utilized to charge a capacitor of 3300 MUF to sustainably
      power four temperature sensors for realizing self-powered temperature sensor
      networks. Moreover, a wireless temperature sensor driven by a hybridized
      nanogenerator charged Li-ion battery can work well to send the temperature data
      to a receiver/computer at a distance of 1.5 m. This work takes a significant step
      toward air-flow energy harvesting and its potential applications in self-powered
      wireless sensor networks. 

PMID- 25844538
TI  - Building allied health workforce capacity: a strategic approach to workforce
      innovation.
AB  - OBJECTIVE: The aim of the present study was to identify areas where allied health
      assistants (AHAs) are not working to their full scope of practice in order to
      improve the effectiveness of the allied health workforce. METHODS: Qualitative
      data collected via focus groups identified suitable AHA tasks and a quantitative
      survey with allied health professionals (AHPs) measured the magnitude of work the
      current AHP workforce spends undertaking these tasks. RESULTS: Quantification
      survey results indicate that Victoria's AHP workforce spends up to 17% of time
      undertaking tasks that could be delegated to an AHA who has relevant training and
      adequate supervision. Over half this time is spent on clinical tasks.
      CONCLUSIONS: The skills of AHAs are not being optimally utilised. Significant
      opportunity exists to reform the current allied health workforce. Such reform
      should result in increased capacity of the workforce to meet future demands.

PMID- 25844541
TI  - Evaluating the Risks of High Altitude Travel in Chronic Liver Disease Patients.
AB  - Luks, Andrew M., and Erik R. Swenson. Clinician's Corner: Evaluating the risks of
      high altitude travel in chronic liver disease patients. High Alt Med Biol 16:80
      88, 2015.--With improvements in the quality of health care, people with chronic
      medical conditions are experiencing better quality of life and increasingly
      participating in a wider array of activities, including travel to high altitude.
      Whenever people with chronic diseases travel to this environment, it is important
      to consider whether the physiologic responses to hypobaric hypoxia will interact
      with the underlying medical condition such that the risk of acute altitude
      illness is increased or the medical condition itself may worsen. This review
      considers these questions as they pertain to patients with chronic liver disease.
      While the limited available evidence suggests there is no evidence of liver
      injury or dysfunction in normal individuals traveling as high as 5000 m, there is
      reason to suspect that two groups of cirrhosis patients are at increased risk for
      problems, hepatopulmonary syndrome patients, who are at risk for severe hypoxemia
      following ascent, and portopulmonary hypertension patients who may be at risk for
      high altitude pulmonary edema and acute right ventricular dysfunction. While
      liver transplant patients may tolerate high altitude exposure without difficulty,
      no information is available regarding the risks of long-term residence at
      altitude with chronic liver disease. All travelers with cirrhosis require careful
      pre-travel evaluation to identify conditions that might predispose to problems at
      altitude and develop risk mitigation strategies for these issues. Patients also
      require detailed counseling about recognition, prevention, and treatment of acute
      altitude illness and may require different medication regimens to prevent or
      treat altitude illness than used in healthy individuals.

PMID- 25844540
TI  - Fully automated fluorescent in situ hybridization (FISH) staining and digital
      analysis of HER2 in breast cancer: a validation study.
AB  - HER2 assessment is routinely used to select patients with invasive breast cancer
      that might benefit from HER2-targeted therapy. The aim of this study was to
      validate a fully automated in situ hybridization (ISH) procedure that combines
      the automated Leica HER2 fluorescent ISH system for Bond with supervised
      automated analysis with the Visia imaging D-Sight digital imaging platform. HER2
      assessment was performed on 328 formalin-fixed/paraffin-embedded invasive breast
      cancer tumors on tissue microarrays (TMA) and 100 (50 selected IHC 2+ and 50
      random IHC scores) full-sized slides of resections/biopsies obtained for
      diagnostic purposes previously. For digital analysis slides were pre-screened at
      20x and 100x magnification for all fluorescent signals and supervised-automated
      scoring was performed on at least two pictures (in total at least 20 nuclei were
      counted) with the D-Sight HER2 FISH analysis module by two observers
      independently. Results were compared to data obtained previously with the manual
      Abbott FISH test. The overall agreement with Abbott FISH data among TMA samples
      and 50 selected IHC 2+ cases was 98.8% (kappa = 0.94) and 93.8% (kappa = 0.88),
      respectively. The results of 50 additionally tested unselected IHC cases were
      concordant with previously obtained IHC and/or FISH data. The combination of the
      Leica FISH system with the D-Sight digital imaging platform is a feasible method
      for HER2 assessment in routine clinical practice for patients with invasive
      breast cancer. 

PMID- 25844539
TI  - Transcriptional profile of Mycobacterium tuberculosis replicating in type II
      alveolar epithelial cells.
AB  - Mycobacterium tuberculosis (M. tb) infection is initiated by the few bacilli
      inhaled into the alveolus. Studies in lungs of aerosol-infected mice provided
      evidence for extensive replication of M. tb in non-migrating, non-antigen
      presenting cells in the alveoli during the first 2-3 weeks post-infection.
      Alveoli are lined by type II and type I alveolar epithelial cells (AEC) which
      outnumber alveolar macrophages by several hundred-fold. M. tb DNA and viable M.
      tb have been demonstrated in AEC and other non-macrophage cells of the kidney,
      liver, and spleen in autopsied tissues from latently-infected subjects from TB
      endemic regions indicating systemic bacterial dissemination during primary
      infection. M. tb have also been demonstrated to replicate rapidly in A549 cells
      (type II AEC line) and acquire increased invasiveness for endothelial cells.
      Together, these results suggest that AEC could provide an important niche for
      bacterial expansion and development of a phenotype that promotes dissemination
      during primary infection. In the current studies, we have compared the
      transcriptional profile of M. tb replicating intracellularly in A549 cells to
      that of M. tb replicating in laboratory broth, by microarray analysis. Genes
      significantly upregulated during intracellular residence were consistent with an
      active, replicative, metabolic, and aerobic state, as were genes for tryptophan
      synthesis and for increased virulence (ESAT-6, and ESAT-6-like genes, esxH, esxJ,
      esxK, esxP, and esxW). In contrast, significant downregulation of the DevR (DosR)
      regulon and several hypoxia-induced genes was observed. Stress response genes
      were either not differentially expressed or were downregulated with the exception
      of the heat shock response and those induced by low pH. The intra-type II AEC M.
      tb transcriptome strongly suggests that AEC could provide a safe haven in which
      M. tb can expand dramatically and disseminate from the lung prior to the
      elicitation of adaptive immune responses. 

PMID- 25844542
TI  - PAH Measurements in Air in the Athabasca Oil Sands Region.
AB  - Polycyclic aromatic hydrocarbon (PAH) measurements were conducted by Wood Buffalo
      Environmental Association (WBEA) at four community ambient Air quality Monitoring
      Stations (AMS) in the Athabasca Oil Sands Region (AOSR) in Northeastern Alberta,
      Canada. The 2012 and 2013 mean concentrations of a subset of the 22 PAH species
      were 9.5, 8.4, 8.8, and 32 ng m(-3) at AMS 1 (Fort McKay), AMS 6 (residential
      Fort McMurray), AMS 7 (downtown Fort McMurray), and AMS 14 (Anzac), respectively.
      The average PAH concentrations in Fort McKay and Fort McMurray were in the range
      of rural and semirural areas, but peak values reflect an industrial emission
      influence. At these stations, PAHs were generally associated with NO, NO2, PM2.5,
      and SO2, indicating the emissions were from the combustion sources such as
      industrial stacks, vehicles, residential heating, and forest fires, whereas the
      PAH concentrations at AMS 14 (~35 km south of Fort McMurray) were more
      characteristic of urban areas with a unique pattern: eight of the lower molecular
      weight PAHs exhibited strong seasonality with higher levels during the warmer
      months. Enthalpies calculated from Clausius-Clapeyron plots for these eight PAHs
      suggest that atmospheric emissions were dominated by temperature-dependent
      processes such as volatilization at warm temperatures. These findings point to
      the potential importance of localized water-air and/or surface-air transfer on
      observed PAH concentrations in air. 

PMID- 25844544
TI  - Non-aqueous Isorefractive Pickering Emulsions.
AB  - Non-aqueous Pickering emulsions of 16-240 MUm diameter have been prepared using
      diblock copolymer worms with ethylene glycol as the droplet phase and an n-alkane
      as the continuous phase. Initial studies using n-dodecane resulted in stable
      emulsions that were significantly less turbid than conventional water-in-oil
      emulsions. This is attributed to the rather similar refractive indices of the
      latter two phases. By utilizing n-tetradecane as an alternative oil that almost
      precisely matches the refractive index of ethylene glycol, almost isorefractive
      ethylene glycol-in-n-tetradecane Pickering emulsions can be prepared. The droplet
      diameter and transparency of such emulsions can be systematically varied by
      adjusting the worm copolymer concentration. 

PMID- 25844543
TI  - Synthesis of a C(1)-C(23) fragment for spirastrellolide E: development of a
      mechanistic rationale for spiroketalization.
AB  - Synthetic analysis of spirastrellolide E envisioned to entail a cross-metathesis
      union of the northern and southern hemispheres followed by a Sharpless
      epoxidation/methylation sequence to achieve the C(22,23) stereogenicity leads to
      the design of a C(1)-C(23) advanced southern hemisphere exploiting a gold
      catalyzed directed spiroketalization as a key step. Stereochemical analysis of
      this strategic transformation provides insight on the impact of the directing
      group carbinol stereogenicity on the reaction efficiency and, in turn, permits
      the conversion of the minor isomer of the spiroketal precursor to the requisite
      congener for successful spiroketalization. 

PMID- 25844545
TI  - p16INK4a immunohistochemical and histopathologic study of Pap test cases
      interpreted as HSIL without CIN2-3 identification in subsequent cervical
      specimens.
AB  - Tissue biopsy following a pap test diagnosis of high grade squamous
      intraepithelial lesion (HSIL) sometimes fails to confirm the presence of a
      corresponding high grade cervical intraepithelial lesion (CIN 2-3), leading to
      confusion as to how best to manage the patient. It has been shown that these
      patients are still at higher risk for future detection of CIN 2-3 even if the
      initial biopsy fails to detect it. It has also been shown that
      immunohistochemical staining for p16INK4a can be reliably used as a surrogate
      marker for infection with high risk human papillomavirus in cervical samples, and
      that it can be used to enhance detection of CIN2-3 in cases where suspicion is
      high. To evaluate the use of p16INK4a staining in cases of HSIL which were not
      confirmed on initial biopsy, two pathologists rereviewed Pap and hematoxylin and
      eosin preparations from all such cases seen within the preceding 3 years.
      Immunohistochemical study for p16INK4a was performed and graded on representative
      sections. The results were tabulated and analyzed. Of the identified 596 HSIL Pap
      cases, 82% had HSIL on initial cervical specimens. Table 1 shows the 56 cases
      included in the study with graded and stratified p16INK4a results. On review of
      the p16INK4a slides, only 2 cases could be upgraded to HSIL/CIN2-3 from the
      original diagnosis. p16INK4a 2-3+ was expressed more frequently in cases
      initially interpreted on Pap as low-grade cervical lesion as compared with benign
      (24 of 35 cases). In the younger than 24-yr-old group p16 2-3+ reactivity was
      more frequent in benign and low-grade cervical lesion/CIN1 groups (benign: 3 of 5
      cases, and CIN1: 6 of 8), and p16 negative reactivity was not seen. p16INK4a was
      graded 0-1+ more frequently in specimens interpreted as benign in the older than
      25 yr olds (10 of 16 cases). The study suggests some diagnostic benefit from the
      use of p16INK4a immunohistochemical study on cervical specimens from women with a
      HSIL Pap test without HSIL/CIN2-3 on original hematoxylin and eosin review. 

PMID- 25844546
TI  - Endocervical adenocarcinoma in situ presenting in fundal endometrial polyp: the
      mother of all skip lesions.
AB  - A 38-yr-old woman, with a previous history of low grade squamous intraepithelial
      lesion in the cervix, presented with heavy menstrual bleeding. At hysteroscopy, a
      fundal polyp was removed from the right cornu which displayed many glands lined
      by atypical, mitotically active epithelium with features characteristic of
      endocervical adenocarcinoma in situ (AIS) of intestinal subtype. Subsequent
      cervical liquid-based cytology and colposcopically directed biopsies revealed no
      causative lesion, but residual PreservCyt from the ThinPrep vial tested positive
      for high risk HPV type other than HPV 16 and 18. Further biopsies from the
      endocervical canal and base of the resected polyp showed intestinal type AIS,
      while all those from the intervening anterior and posterior endometrial lining
      exhibited normal endometrium only. Genomic DNA extracted from the endometrial
      polyp and second set of endocervical biopsies tested positive for HPV 31, an
      uncommon cause of endocervical glandular neoplasia. Endocervical AIS typically
      arises in the transformation zone but may be found exclusively in the
      endocervical canal and rarely as high as 30 mm from the ectocervix. Contiguous
      spread into the lower uterine segment is known to occur, as are proximate so
      called skip lesions. However, finding a 'skip' lesion 80 mm from the
      transformation zone poses an interesting pathogenetic conundrum as well as a
      therapeutic dilemma in a young patient desirous of retaining fertility. Issues
      relating to pathogenesis include necessary metaplasia of the endometrial
      glandular epithelium to 'susceptible' endocervical type epithelium within the
      polyp or metastatic implantation of transformed endocervical glandular cells onto
      the polyp. The current management plan involves regular hysteroscopic
      surveillance of the uterine cavity.

PMID- 25844547
TI  - Dyssynchronous secretory endometrial glands often show sporadically acquired
      progesterone nonresponsiveness.
AB  - Primary sporadic gene-inactivating events within the progesterone response
      cascade might explain the presence of individual dyssynchronous (outlier) glands
      commonly observed in a secretory background. We queried morphologically
      dyssynchronous glands in mid-secretory endometrium with a series of markers
      normally downregulated by progesterone. Seventy-nine mid-secretory endometrial
      biopsies were stained with hematoxylin and eosin, MIB-1, PAX2, estrogen and
      progesterone receptors, and PTEN. Aberrant staining of glands was independently
      scored for each marker. Outlier glands overlapping between stains were
      enumerated. A total of 63% of cases had hematoxylin and eosin stained outlier
      glands (average 9), which often demonstrated failed progesterone-mediated
      downregulation of PAX2 (43%), estrogen (40%), and/or progesterone receptors
      (28%). Aberrations of progesterone response was seen in 70% to 85% of cases
      overall, averaging 10 to 30 glands/affected case. The frequency and burden of
      affected glands was similar to that seen for primary inactivating events of the
      PAX2 and PTEN genes (35% and 41% of cases, respectively, averaging 32 and 38
      glands per affected patient). Sporadic gene-inactivating events are common during
      endometrial regeneration, and may cause morphologic changes unmasked by the
      hormonal context. Some of these dyssynchronous "outlier" glands, whether evident
      on hematoxylin and eosin stain or not, have an interrupted progesterone response.

PMID- 25844548
TI  - Partial hydatidiform mole with extensive angiomatoid vessel configuration in a
      first trimester miscarriage.
AB  - We report a first trimester miscarriage (9 wk gestation) with a macroscopic grape
      like aspect due to extensive angiomatoid changes with widened communicating thin
      walled villous vessels. Fluorescence in situ hybridization analysis and
      microsatellite analysis revealed a diandric triploidy of the trophoblastic
      tissue, so this miscarriage is indeed a genetic partial hydatidiform mole. This
      is remarkable since the typical morphologic hallmarks of partial hydatidiform
      mole, especially enhanced trophoblastic proliferation and marked villous cistern
      formation, were not prominent. The finding of extensive angiomatoid morphology is
      to our knowledge an undescribed morphology of an early partial hydatidiform mole.
      It serves as an example of the morphologic variability of this probably
      underestimated condition that has a slightly elevated risk for the development of
      gestational trophoblastic disease. 

PMID- 25844549
TI  - Simultaneous carcinomas of the breast and ovary: utility of Pax-8, WT-1, and
      GATA3 for distinguishing independent primary tumors from metastases.
AB  - Breast carcinomas rarely metastasize to the ovary and are even more rarely
      present clinically as primary ovarian tumors. However, patients with breast
      cancer not infrequently develop independent primary ovarian carcinomas. In these
      cases, distinction between independent primaries and metastatic tumors is
      crucial. Several comparative immunohistochemical studies have been reported, but
      few included significant clinicopathologic data and none investigated cases of
      ovarian and breast carcinomas from the same patients. In this study, we compared
      18 cases of patients with bona fide independent breast and ovarian carcinomas (15
      high-grade serous and 3 clear cell carcinomas), with 9 cases of patients with
      known mammary carcinomas (7 lobular and 2 ductal carcinomas) metastatic to the
      ovary. Immunohistochemical stains for Pax-8, WT-1, and GATA3 were carried out on
      tissue microarrays (TMA). Most primary ovarian carcinomas were larger than the
      metastatic tumors (P=0.001) and were diagnosed at an advanced stage. All primary
      ovarian tumors showed marked nuclear pleomorphism, whereas only 2 metastatic
      breast carcinomas had Grade 3 nuclei (P=0.000). The vast majority of ovarian
      metastases (7/9) showed the typical pattern of lobular breast carcinoma. Pax-8
      and WT-1 expression were found in 16 of 18 (88%) and 13 of 18 (72%) primary
      ovarian carcinomas, respectively. In contrast, all primary ovarian carcinomas
      were negative for GATA3. The 2 Pax-8-negative ovarian carcinomas were also
      negative for WT-1. With the exception of 3 triple-negative carcinomas, all
      primary breast carcinomas were positive for GATA3. All metastatic breast
      carcinomas were positive for GATA3 and negative for Pax-8. WT-1 expression was
      seen in only 1 of 9 metastatic breast carcinomas (11%). Patients with ovarian
      metastases had worse prognosis than patients with independent breast and ovarian
      carcinomas (P=0.000). Pax-8, WT-1, and GATA3 immunoreactions are useful in the
      distinction between independent primaries and metastatic mammary carcinomas to
      the ovary in the light of clinicopathologic findings. 

PMID- 25844550
TI  - Ovarian sex cord-stromal tumors in patients with probable or confirmed germline
      DICER1 mutations.
AB  - The DICER1 gene encodes an endoribonuclease involved in the production of mature
      microRNAs which regulates gene expression through several mechanisms. Recent
      studies have demonstrated somatic mutations in DICER1 in approximately 60% of
      ovarian Sertoli-Leydig cell tumors. Furthermore, patients with germline mutations
      in DICER1 are predisposed to developing a range of rare neoplasms including
      ovarian sex cord-stromal tumors most of which have been classified as Sertoli
      Leydig cell tumor. However, the histologic features of these tumors have not been
      reported in detail. We describe the morphologic and immunophenotypic findings of
      4 sex cord-stromal tumors arising in patients with proven or likely germline
      DICER1 mutations including 3 individuals from 1 family. Three tumors showed
      similar appearances characterized by marked architectural and cytologic
      heterogeneity including sertoliform, juvenile granulosa cell tumor-like, and
      unclassifiable elements. The remaining case mainly showed heterologous mucinous
      epithelial and neuroendocrine differentiation with only a minor intermediate
      grade Sertoli cell component. This tumor and one of the 3 former cases arose in
      related patients with identical germline DICER1 mutations indicating that
      additional factors influence tumor morphology. All tumors were positive for
      steroidogenic factor-1 and FOXL2 on immunohistochemical analysis, whereas there
      was more variable expression of inhibin, calretinin, CD56, CD99, and hormone
      receptors. The present small series suggests that some ovarian Sertoli-Leydig
      cell tumor associated with germline DICER1 mutations may show distinctive
      histologic features in particular admixed Sertoli cell and juvenile granulosa
      cell tumor-like features. Larger studies are required to establish whether
      heterologous elements are also a more common feature of these tumors. 

PMID- 25844551
TI  - Article by Natalie Banet and Robert J. Kurman: Two types of ovarian cortical
      inclusion cysts: proposed origin and possible role in ovarian serous
      carcinogenesis; Int. J. Gynecol. Pathol. 2015;34:3-8.

PMID- 25844552
TI  - Re: Article by Natalie Banet and Robert J. Kurman: Two types of ovarian cortical
      inclusion cysts: proposed origin and possible role in ovarian serous
      carcinogenesis; Int. J. Gynecol. Pathol. 2015;34:3-8.

PMID- 25844553
TI  - History of gynecologic pathology XXVII: Dr Herbert Bradley Taylor.

PMID- 25844554
TI  - Optimization of ultrasound-assisted extraction of pectinase enzyme from guava
      (Psidium guajava) peel: Enzyme recovery, specific activity, temperature, and
      storage stability.
AB  - This study aimed to investigate the effects of the ultrasound-assisted extraction
      conditions on the yield, specific activity, temperature, and storage stability of
      the pectinase enzyme from guava peel. The ultrasound variables studied were
      sonication time (10-30 min), ultrasound temperature (30-50  degrees C), pH (2.0
      8.0), and solvent-to-sample ratio (2:1 mL/g to 6:1 mL/g). The main goal was to
      optimize the ultrasound-assisted extraction conditions to maximize the recovery
      of pectinase from guava peel with the most desirable enzyme-specific activity and
      stability. Under the optimum conditions, a high yield (96.2%), good specific
      activity (18.2 U/mg), temperature stability (88.3%), and storage stability
      (90.3%) of the extracted enzyme were achieved. The optimal conditions were 20 min
      sonication time, 40  degrees C temperature, at pH 5.0, using a 4:1 mL/g solvent
      to-sample ratio. The study demonstrated that optimization of ultrasound-assisted
      process conditions for the enzyme extraction could improve the enzymatic
      characteristics and yield of the enzyme.

PMID- 25844555
TI  - A classification of chronic pain for ICD-11.

PMID- 25844557
TI  - Energetic-Energetic Cocrystals of Diacetone Diperoxide (DADP): Dramatic and
      Divergent Sensitivity Modifications via Cocrystallization.
AB  - Here we report a series of energetic-energetic cocrystals that incorporate the
      primary explosive diacetone diperoxide (DADP) with a series of
      trihalotrinitrobenzene explosives: 1:1 DADP/1,3,5-trichloro-2,4,6-trinitrobenzene
      (TCTNB), 1:1 DADP/1,3,5-tribromo-2,4,6-trinitrobenzene (TBTNB), and 1:1
      DADP/1,3,5-triiodo-2,4,6-trinitrobenzene (TITNB). Acetone peroxides are
      attractive for their inexpensive and facile synthesis, but undesirable properties
      such as poor stability, intractably high sensitivity and low density, an
      indicator for low explosive power, have limited their application. Here through
      cocrystallization the density, oxygen balance, and stability of DADP are
      dramatically improved. Regarding sensitivity, in the case of the DADP/TCTNB
      cocrystal, the high impact sensitivity of DADP is retained by the cocrystal,
      making it a denser and less volatile form of DADP that remains viable as a
      primary explosive. Conversely, the DADP/TITNB cocrystal features impact
      sensitivity that is greatly reduced relative to both pure DADP and pure TITNB,
      demonstrating for the first time an energetic cocrystal that is less sensitive to
      impact than either of its pure components. This dramatic difference in cocrystal
      sensitivities may stem from the significantly different halogen-peroxide
      interactions seen in each cocrystal structure. These results highlight how
      sensitivity is defined by complex relationships between inherent bond strengths
      and solid-state properties, and cocrystal series such as that presented here
      provide a powerful experimental platform to probe this relationship. 

PMID- 25844556
TI  - Impaired Muscle Mitochondrial Biogenesis and Myogenesis in Spinal Muscular
      Atrophy.
AB  - IMPORTANCE: The important depletion of mitochondrial DNA (mtDNA) and the general
      depression of mitochondrial respiratory chain complex levels (including complex
      II) have been confirmed, implying an increasing paucity of mitochondria in the
      muscle from patients with types I, II, and III spinal muscular atrophy (SMA-I, 
      II, and -III, respectively). OBJECTIVE: To investigate mitochondrial dysfunction
      in a large series of muscle biopsy samples from patients with SMA. DESIGN,
      SETTING, AND PARTICIPANTS: We studied quadriceps muscle samples from 24 patients
      with genetically documented SMA and paraspinal muscle samples from 3 patients
      with SMA-II undergoing surgery for scoliosis correction. Postmortem muscle
      samples were obtained from 1 additional patient. Age-matched controls consisted
      of muscle biopsy specimens from healthy children aged 1 to 3 years who had
      undergone analysis for suspected myopathy. Analyses were performed at the
      Neuromuscular Unit, Istituto di Ricovero e Cura a Carattere Scientifico
      Foundation Ca' Granda Ospedale Maggiore Policlinico-Milano, from April 2011
      through January 2015. EXPOSURES: We used histochemical, biochemical, and
      molecular techniques to examine the muscle samples. MAIN OUTCOMES AND MEASURES:
      Respiratory chain activity and mitochondrial content. RESULTS: Results of
      histochemical analysis revealed that cytochrome-c oxidase (COX) deficiency was
      more evident in muscle samples from patients with SMA-I and SMA-II. Residual
      activities for complexes I, II, and IV in muscles from patients with SMA-I were
      41%, 27%, and 30%, respectively, compared with control samples (P < .005). Muscle
      mtDNA content and cytrate synthase activity were also reduced in all 3 SMA types
      (P < .05). We linked these alterations to downregulation of peroxisome
      proliferator-activated receptor coactivator 1alpha, the transcriptional
      activators nuclear respiratory factor 1 and nuclear respiratory factor 2,
      mitochondrial transcription factor A, and their downstream targets, implying
      depression of the entire mitochondrial biogenesis. Results of Western blot
      analysis confirmed the reduced levels of the respiratory chain subunits that
      included mitochondrially encoded COX1 (47.5%; P = .004), COX2 (32.4%; P < .001),
      COX4 (26.6%; P < .001), and succinate dehydrogenase complex subunit A (65.8%; P =
      .03) as well as the structural outer membrane mitochondrial porin (33.1%; P <
      .001). Conversely, the levels of expression of 3 myogenic regulatory factors
      muscle-specific myogenic factor 5, myoblast determination 1, and myogenin-were
      higher in muscles from patients with SMA compared with muscles from age-matched
      controls (P < .05). CONCLUSIONS AND RELEVANCE: Our results strongly support the
      conclusion that an altered regulation of myogenesis and a downregulated
      mitochondrial biogenesis contribute to pathologic change in the muscle of
      patients with SMA. Therapeutic strategies should aim at counteracting these
      changes.

PMID- 25844558
TI  - A comparison of self-reported sexual risk behaviours between US civilian and
      active duty military women.
AB  - Women in the US military report a high prevalence of sexual risk behaviours, such
      as binge drinking and new or multiple sexual partnerships. However, demographical
      differences pose challenges to making comparisons with civilians. Two public-use
      datasets were used to compare prevalence of sexual risk behaviours between
      sexually active military and civilian women, after adjusting for demographic
      factors. It was found that women in the military reported a higher prevalence of
      binge drinking and new/multiple sexual partners as compared with civilians, which
      suggests that military women are a high-risk group and the military environment
      may at least partially facilitate these risk behaviours. 

PMID- 25844559
TI  - Malignant (Diffuse) Mesothelioma in Patients With Hematologic Malignancies: A
      Clinicopathologic Study of 45 Cases.
AB  - CONTEXT: Ionizing radiation has a role in the development of malignant
      mesothelioma, in several epidemiologic studies, including patients with
      hematologic malignancies. OBJECTIVE: To study the clinicopathologic
      characteristics of patients with malignant mesothelioma and hematologic
      malignancies with and without a history of radiotherapy. DESIGN: From a database
      of approximately 3600 patients with malignant mesothelioma, we identified 45
      patients (1%) who also had hematologic malignancies. We examined
      clinicopathologic features and noted whether the patient had received
      radiotherapy for malignancy, comparing those with and those without such
      exposure. RESULTS: Among the 45 cases, 18 (40%) had Hodgkin lymphoma, 15 (33%)
      had non-Hodgkin lymphoma, 10 (4%) had chronic lymphocytic leukemia, and 2 (22%)
      had chronic myelogenous leukemia; 20 patients (44%) had a history of
      radiotherapy, and 23 (51%) did not. Most patients with Hodgkin lymphoma (16 of
      18; 90.0%) received radiation, whereas none of the patients with leukemia (0 of
      12) and only 20% (3 of 15) of the patients with non-Hodgkin lymphoma did so.
      Patients without radiation were older than patients who received radiotherapy
      (median, 73 versus 54 years, respectively; P < .001), had a shorter interval from
      diagnosis of hematologic malignancy to that of mesothelioma (median, 2 versus 24
      years, respectively; P < .001), and had a shorter survival period (median, 6.0
      versus 14.0 months, respectively; P = .02). Epithelial mesotheliomas were
      proportionately more common in patients with a history of radiotherapy.
      CONCLUSIONS: Patients with mesothelioma and hematologic malignancies with a
      history of radiation tended to be younger, had a longer interval from diagnosis
      of hematologic malignancy to that of mesothelioma, had a longer survival period,
      and were more likely to have the epithelial variant compared with patients
      without radiotherapy.

PMID- 25844560
TI  - A Pilot Study on the Influence of Facial Expression on Measurements in Three
      Dimensional Digital Surfaces of the Face in Infants With Cleft Lip and Palate.
AB  - OBJECTIVE: Three-dimensional surface imaging is an increasingly popular modality
      for face measurements in infants with cleft lip and palate. Infants are
      noncompliant toward producing specific facial expressions, and selecting the
      appropriate moment of acquisition is challenging. The objective was to estimate
      amount and spatial distribution of deformation of the face due to facial
      expression in infants with cleft lip and palate and provide recommendations for
      an improved acquisition protocol, including a method of quality control in terms
      of obtaining images with true neutral expression. MATERIAL AND METHODS: Three
      dimensional surface images of ten 4-month-old infants with unrepaired cleft lip
      and palate were obtained using a 3dMDface stereophotogrammetric system. For each
      subject, five surface images judged as representing a neutral expression were
      obtained during the same photo session. Mean and maximum deformations were
      calculated. A formalized review was performed, allowing the image exhibiting the
      "best" neutral expression to be selected, thus decreasing errors due to residual
      facial expression. RESULTS: Deformation due to facial expression generally
      increased from forehead to chin. The amount of deformation in three selected
      regions were determined: nose (mean, 1 mm; maximum = 3 mm); cleft region (mean, 2
      mm; maximum = 5 mm); chin region (mean, 5 mm; maximum = 12 mm). Analysis
      indicated that introduction of a formalized review of images could reduce these
      errors by a factor of 2. CONCLUSIONS: The continuous change of facial expression
      in infants represents a substantial source of error; however, this may be reduced
      by incorporating a formalized review into the acquisition protocol.

PMID- 25844561
TI  - Primary Palatoplasty for Unilateral Cleft Lip and Palate Using Mucosal Grafts and
      Flaps.
AB  - The mucosal graft and flaps method (MG method) is a palatoplasty technique that
      was developed for the purpose of improving maxillary growth in patients with
      cleft palate. In the MG method, full-thickness buccal mucosa is grafted onto the
      raw surface created by pushback palatoplasty. The method is unlikely to result in
      severe scarring and has a favorable effect on maxillary growth. In addition, it
      is unlikely to result in oronasal fistula and provides good speech results.
      Overall, postive long-term treatment results have been obtained. Although the MG
      method is technically difficult and requires a lengthy surgery, the technique is
      considered to be effective for palate closure in terms of speech and maxillary
      growth.

PMID- 25844562
TI  - The Americleft Project: A Proposed Expanded Nasolabial Appearance Yardstick for 5
      to 7-Year-Old Patients With Complete Unilateral Cleft Lip and Palate (CUCLP).
AB  - OBJECTIVE: To develop a yardstick of reference photographs for nasolabial
      appearance assessments of 5- to 7-year-old patients with complete unilateral
      cleft lip and palate (CUCLP). DESIGN: Blind retrospective analysis of clinical
      records and comparison to historical controls. PATIENTS: Subjects were two groups
      of 6- to 12-year-olds (n = 124 and n = 135) and one group of 5- to 7-year-olds (n
      = 149) with nonsyndromic CUCLP from three previous Americleft studies, including
      cohorts from seven different cleft/craniofacial centers. INTERVENTIONS: All
      patients received the infant management protocols of their respective centers.
      Eleven trained and calibrated judges (five participated in all three studies) did
      blind ratings of nasolabial appearance using the Asher-McDade method. MAIN
      OUTCOME MEASURES: Patients receiving the most consistent ratings between judges,
      selected first from the groups of 6- to 12-year-olds, were used to create a pilot
      yardstick for eventual use in the third study of 5- to 7-year-olds. For each of
      the Asher-McDade categories, 8 of the 5- to 7-year-old patients receiving the
      most consistent scores between raters were ranked by 10 judges for a final
      elimination to leave three per category. RESULTS: Using this method of successive
      changes in rating methods, a new reference yardstick for nasolabial appearance
      rating was established and linked to the original Asher-McDade method as well as
      the single examples in a previously published yardstick for patients with CUCLP.
      Pilot testing using the yardstick improved reliabilities. CONCLUSIONS: Use of an
      expanded nasolabial yardstick of reference photographs representative of the
      range of possibilities of each of the five Asher-McDade categories is now
      available to see if reliability of these ratings can be improved.

PMID- 25844564
TI  - Adolescent Turkish migrants' eating behavior in Germany: A comparison to
      nonmigrants in the home and host countries based on the prototype-willingness
      model.
AB  - OBJECTIVES: The aim of the present research was to examine the regulation of
      eating behavior among adolescents with a Turkish migration background living in
      Germany in comparison with adolescent nonmigrants from the host (Germany) and
      home country (Turkey). The prototype-willingness model (PWM) was chosen and
      analyzed with respect to differences in mean levels and predictions of its social
      cognitive factors. METHOD: Two studies were conducted. Study 1 was longitudinal
      with 131 adolescent Turkish migrants and 303 Germans, whereas Study 2 was cross
      sectional with 102 adolescent Turkish migrants and 270 Turks. Sociodemographic
      information, PWM variables, and eating behavior were enquired via questionnaire.
      Group differences in means and prediction patterns were analyzed using multiple
      group structural equation modeling. Analyses were conducted separately
      introducing PWM variables to eat either unhealthy (unhealthy model) or healthy
      foods (healthy model). RESULTS: The studies show consistent differences in means
      and predictions between Turkish migrants and Germans as well as Turks. The
      regulation of Turkish migrants' eating behavior was found to be intentional,
      whereas Germans and Turks showed both an impulsive and intentional regulation.
      CONCLUSIONS: Effective interventions on healthy eating for Turkish migrants need
      to be tailored according to their specific regulation of eating behavior.

PMID- 25844565
TI  - Development and validation of the African American Women's Shifting Scale
      (AAWSS).
AB  - OBJECTIVE: The purpose of this research was to develop and validate an instrument
      to measure shifting or self-altering strategies among African American women.
      METHOD: A 13-item instrument was developed to measure aspects of shifting
      phenomena based on the empirical literature, feedback from focus groups, and
      cultural experts. The initial validation study, using principal axis analysis,
      was conducted with a national sample of 318 African American women. A second
      independent national sample of 190 African American women provided data for a
      confirmatory factor analysis. RESULTS: Results indicated that the inventory was
      composed of the following 3 factors: Strong Black Woman, Awareness of Shifting
      Behavior, and Sensitivity to the Perceptions of Blacks. CONCLUSIONS: A structural
      model was developed based on the Multicultural Assessment-Intervention Process
      (MAIP) framework that allowed for the exploration of the shifting construct.
      Implications for future research are discussed.

PMID- 25844567
TI  - Competing mortality in cancer screening: a teachable moment.

PMID- 25844568
TI  - Roster process review: a case study on the implications of preliminary findings.
AB  - Rostering is an important process to enable efficient, effective and safe
      delivery of health care, and one which receives little attention. The work
      outlined in this case study demonstrates that the analysis of rostering processes
      from a range of perspectives including the organisation, staff and the roster
      manager can identify significant opportunities for improvement. Roster governance
      is not universally applied, nor understood, which can result in dissonant
      expectations between managers and staff and a lack of transparency in how and why
      decisions about rostering are made. Redesigning roster processes can promote more
      effective governance and improve organisational efficiency.

PMID- 25844566
TI  - Impact of lifetime evaluated need on mental health service use among African
      American emerging adults.
AB  - OBJECTIVE: This study investigated the association between evaluated need and
      mental health service use among African-American emerging adults, when
      controlling for other predictor variables. METHOD: Secondary analysis of data
      from the National Survey of American Life (2001-2003) was conducted. A nationally
      representative sample of African-American emerging adults, ages 18 to 29 years (N
      = 806), was assessed with the Composite International Diagnostic Interview. The
      sample included females and males with a mean age of 23 years. Evaluated need was
      determined by endorsement of mood, anxiety, substance use, or impulse control
      diagnoses. Respondents who reported ever voluntarily using mental health or
      general medical services to address these problems were considered to have used
      services. RESULTS: Forty-seven percent of the sample demonstrated an evaluated
      need for services, whereas a quarter of the sample used services in their
      lifetime. Respondents who were females, had received religious/spiritual support,
      and who had an evaluated need for services were significantly more likely to have
      used services in their lifetime compared with males, those who had not received
      religious/spiritual support, and those without a need for services. CONCLUSIONS:
      Literature indicates that evaluated need is a strong predictor of mental health
      service use, yet research examining its impact on service use among African
      American emerging adults is limited. This study found that along with having an
      evaluated need, this population was more likely to use services when supported by
      a religious/spiritual leader. Mental health outreach and education that
      incorporates the informal support systems identified by African American emerging
      adults, particularly males, is needed.

PMID- 25844569
TI  - Patient beliefs and behaviors about genomic risk for type 2 diabetes:
      implications for prevention.
AB  - Type 2 diabetes is a major health burden in the United States, and population
      trends suggest this burden will increase. High interest in, and increased
      availability of, testing for genetic risk of type 2 diabetes presents a new
      opportunity for reducing type 2 diabetes risk for many patients; however, to
      date, there is little evidence that genetic testing positively affects type 2
      diabetes prevention. Genetic information may not fit patients' illness
      representations, which may reduce the chances of risk-reducing behavior changes.
      The present study aimed to examine illness representations in a clinical sample
      who are at risk for type 2 diabetes and interested in genetic testing. The
      authors used the Common Sense Model to analyze survey responses of 409 patients
      with type 2 diabetes risk factors. Patients were interested in genetic testing
      for type 2 diabetes risk and believed in its importance. Most patients believed
      that genetic factors are important to developing type 2 diabetes (67%), that diet
      and exercise are effective in preventing type 2 diabetes (95%), and that
      lifestyle changes are more effective than drugs (86%). Belief in genetic
      causality was not related to poorer self-reported health behaviors. These results
      suggest that patients' interest in genetic testing for type 2 diabetes might
      produce a teachable moment that clinicians can use to counsel behavior change. 

PMID- 25844570
TI  - Catch-up growth in low-birthweight infants: friend or foe?

PMID- 25844571
TI  - Phytomedicines (medicines derived from plants) for sickle cell disease.
AB  - BACKGROUND: Sickle cell disease, a common recessively inherited haemoglobin
      disorder, affects people from sub-Saharan Africa, the Middle East, Mediterranean
      basin, Indian subcontinent, Caribbean and South America. It is associated with
      complications and a reduced life expectancy. Phytomedicines (medicine derived
      from plants in their original state) encompass many of the plant remedies from
      traditional healers which the populations most affected would encounter. There
      has been little systematic appraisal of their benefits. This is an update of a
      Cochrane Review first published in 2010 and updated in 2013. OBJECTIVES: To
      assess the benefits and risks of phytomedicines in people with sickle cell
      disease of all types, of any age, in any setting. SEARCH METHODS: We searched the
      Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials
      Register, the International Standard Randomised Controlled Trial Number Register
      (ISRCTN) and the Allied and Complimentary Medicine Database (AMED).Dates of most
      recent searches: Haemoglobinopathies Trials Register: 13 October 2014; ISRCTN: 17
      January 2015; AMED: 20 January 2015. SELECTION CRITERIA: Randomised or quasi
      randomised trials with participants of all ages with sickle cell disease, in all
      settings, comparing the administration of phytomedicines, by any mode to placebo
      or conventional treatment, including blood transfusion and hydroxyurea. DATA
      COLLECTION AND ANALYSIS: Both authors independently assessed trial quality and
      extracted data. MAIN RESULTS: Two trials (182 participants) and two
      phytomedicines Niprisan((r)) (also known as Nicosan((r))) and Ciklavit((r)) were
      included. The Phase IIB (pivotal) trial suggests that Niprisan((r)) was effective
      in reducing episodes of severe painful sickle cell disease crisis over a six
      month period. It did not affect the risk of severe complications or the level of
      anaemia. No serious adverse effects were reported. The single trial of Cajanus
      cajan (Ciklavit((r))) reported a possible benefit to individuals with painful
      crises, and a possible adverse effect (non-significant) on the level of anaemia.
      AUTHORS' CONCLUSIONS: While Niprisan((r)) appeared to be safe and effective in
      reducing severe painful crises over a six-month follow-up period, further trials
      are required to assess its role in the management of people with sickle cell
      disease and the results of its multicentre trials are awaited. Currently no
      conclusions can be made regarding the efficacy of Ciklavit((r)). Based on the
      published results for Niprisan((r)) and in view of the limitations in data
      collection and analysis of both trials, phytomedicines may have a potential
      beneficial effect in reducing painful crises in sickle cell disease. This needs
      to be further validated in future trials. More trials are required on the safety
      and efficacy of phytomedicines used in managing sickle cell disease.

PMID- 25844572
TI  - Is dissonance reduction a special case of fluid compensation? Evidence that
      dissonant cognitions cause compensatory affirmation and abstraction.
AB  - Cognitive dissonance theory shares much in common with other perspectives that
      address anomalies, uncertainty, and general expectancy violations. This has led
      some theorists to argue that these theories represent overlapping psychological
      processes. If responding to dissonance and uncertainty occurs through a common
      psychological process, one should expect that the behavioral outcomes of feeling
      uncertain would also apply to feelings of dissonance, and vice versa. One
      specific prediction from the meaning maintenance model would be that cognitive
      dissonance, like other expectancy violations, should lead to the affirmation of
      unrelated beliefs, or the abstraction of unrelated schemas when the dissonant
      event cannot be easily accommodated. This article presents 4 studies (N = 1124)
      demonstrating that the classic induced-compliance dissonance paradigm can lead
      not only to a change of attitudes (dissonance reduction), but also to (a) an
      increased reported belief in God (Study 2), (b) a desire to punish norm-violators
      (Study 1 and 3), (c) a motivation to detect patterns amid noise (Study 3), and
      (d) polarizing support of public policies among those already biased toward a
      particular side (Study 4). These results are congruent with theories that propose
      content-general fluid compensation following the experience of anomaly, a finding
      not predicted by dissonance theory. The results suggest that dissonance reduction
      behaviors may share psychological processes described by other theories
      addressing violations of expectations.

PMID- 25844573
TI  - Stereotype validation: the effects of activating negative stereotypes after
      intellectual performance.
AB  - With regard to intellectual performance, a large body of research has shown that
      stigmatized group members may perform more poorly when negative, self-relevant
      stereotypes become activated prior to a task. However, no research to date has
      identified the potential ramifications of stereotype activation that happens
      after-rather than before-a person has finished performing. Six studies examined
      how postperformance stereotype salience may increase the certainty individuals
      have in evaluations of their own performance. In the current research, the
      accessibility of gender or racial stereotypes was manipulated after participants
      completed either a difficult math test (Studies 1-5) or a test of child-care
      knowledge (Study 6). Consistent with predictions, stereotype activation was found
      to increase the certainty that women (Studies 1, 2, 4, and 5), African Americans
      (Study 3), and men (Study 6) had toward negative evaluations of their own test
      performance. These effects emerged when performance-related perceptions were
      stereotype consistent rather than inconsistent (Studies 1-6) and were found to be
      most pronounced among those who were highly identified with the stereotyped group
      (Study 5). Furthermore, greater certainty-triggered by negative stereotypes
      predicted lowered domain-relevant beliefs (Studies 1, 2, 3, and 6) and
      differential exposure to domain-relevant stimuli (Studies 4 and 5).

PMID- 25844574
TI  - Using the IAT to predict ethnic and racial discrimination: small effect sizes of
      unknown societal significance.
AB  - Greenwald, Banaji, and Nosek (2015) present a reanalysis of the meta-analysis by
      Oswald, Mitchell, Blanton, Jaccard, and Tetlock (2013) that examined the effect
      sizes of Implicit Association Tests (IATs) designed to predict racial and ethnic
      discrimination. We discuss points of agreement and disagreement with respect to
      methods used to synthesize the IAT studies, and we correct an error by Greenwald
      et al. that obscures a key contribution of our meta-analysis. In the end, all of
      the meta-analyses converge on the conclusion that, across diverse methods of
      coding and analyzing the data, IAT scores are not good predictors of ethnic or
      racial discrimination, and explain, at most, small fractions of the variance in
      discriminatory behavior in controlled laboratory settings. The thought
      experiments presented by Greenwald et al. go well beyond the lab to claim
      systematic IAT effects in noisy real-world settings, but these hypothetical
      exercises depend crucially on untested and, arguably, untenable assumptions.

PMID- 25844575
TI  - "Two souls, two thoughts," two self-schemas: double consciousness can have
      positive academic consequences for African Americans.
AB  - African Americans can experience a double consciousness-the two-ness of being an
      American and an African American. The present research hypothesized that: (a)
      double consciousness can function as 2 self-schemas-an independent self-schema
      tied to mainstream American culture and an interdependent self-schema tied to
      African American culture, and (b) U.S. educational settings can leverage an
      interdependent self-schema associated with African American culture through
      inclusive multicultural practices to facilitate positive academic consequences.
      First, a pilot experiment and Studies 1 and 2 provided evidence that double
      consciousness can be conceptualized as 2 self-schemas. That is, African Americans
      shifted their behavior (e.g., cooperation) in schema-relevant ways from more
      independent when primed with mainstream American culture to more interdependent
      when primed with African American culture. Then, Studies 3 and 4 demonstrated
      that incorporating African American culture within a university setting enhanced
      African Americans' persistence and performance on academic-relevant tasks.
      Finally, using the Gates Millennium Scholars dataset (Cohort 1), Study 5
      conceptually replicated Studies 3 and 4 and provided support for one process that
      underlies the observed positive academic consequences. Specifically, Study 5
      provided evidence that engagement with African American culture (e.g.,
      involvement with cultural events/groups) on college campuses makes an
      interdependent self-schema more salient that increases African American students'
      sense of academic fit and identification, and, in turn, enhances academic
      performance (self-reported grades) and persistence (advanced degree enrollment in
      a long-term follow-up). The discussion examines double consciousness as a basic
      psychological phenomenon and suggests the intra- and intergroup benefits of
      inclusive multicultural settings.

PMID- 25844576
TI  - Having "been there" doesn't mean I care: when prior experience reduces compassion
      for emotional distress.
AB  - The current research found that participants who had previously endured an
      emotionally distressing event (e.g., bullying) more harshly evaluated another
      person's failure to endure a similar distressing event compared with participants
      with no experience enduring the event or those currently enduring the event.
      These effects emerged for naturally occurring (Studies 1, 3, and 4) and
      experimentally induced (Study 2) distressing events. This effect was driven by
      the tendency for those who previously endured the distressing event to view the
      event as less difficult to overcome (Study 3). Moreover, we demonstrate that the
      effect is specific to evaluations of perceived failure: Compared with those with
      no experience, people who previously endured a distressing event made less
      favorable evaluations of an individual failing to endure the event, but made more
      favorable evaluations of an individual managing to endure the event (Study 4).
      Finally, we found that people failed to anticipate this effect of enduring
      distress, instead believing that individuals who have previously endured
      emotionally distressing events would most favorably evaluate others' failures to
      endure (Study 5). Taken together, these findings present a paradox such that, in
      the face of struggle or defeat, the people we seek for advice or comfort may be
      the least likely to provide it.

PMID- 25844577
TI  - Implicit theories about willpower predict self-regulation and grades in everyday
      life.
AB  - Laboratory research shows that when people believe that willpower is an abundant
      (rather than highly limited) resource they exhibit better self-control after
      demanding tasks. However, some have questioned whether this "nonlimited" theory
      leads to squandering of resources and worse outcomes in everyday life when
      demands on self-regulation are high. To examine this, we conducted a longitudinal
      study, assessing students' theories about willpower and tracking their self
      regulation and academic performance. As hypothesized, a nonlimited theory
      predicted better self-regulation (better time management and less
      procrastination, unhealthy eating, and impulsive spending) for students who faced
      high self-regulatory demands. Moreover, among students taking a heavy course
      load, those with a nonlimited theory earned higher grades, which was mediated by
      less procrastination. These findings contradict the idea that a limited theory
      helps people allocate their resources more effectively; instead, it is people
      with the nonlimited theory who self-regulate well in the face of high demands.

PMID- 25844578
TI  - Dual passivation of intrinsic defects at the compound semiconductor/oxide
      interface using an oxidant and a reductant.
AB  - Studies have shown that metal oxide semiconductor field-effect transistors
      fabricated utilizing compound semiconductors as the channel are limited in their
      electrical performance. This is attributed to imperfections at the
      semiconductor/oxide interface which cause electronic trap states, resulting in
      inefficient modulation of the Fermi level. The physical origin of these states is
      still debated mainly because of the difficulty in assigning a particular
      electronic state to a specific physical defect. To gain insight into the exact
      source of the electronic trap states, density functional theory was employed to
      model the intrinsic physical defects on the InGaAs (2 * 4) surface and to model
      the effective passivation of these defects by utilizing both an oxidant and a
      reductant to eliminate metallic bonds and dangling-bond-induced strain at the
      interface. Scanning tunneling microscopy and spectroscopy were employed to
      experimentally determine the physical and electronic defects and to verify the
      effectiveness of dual passivation with an oxidant and a reductant. While
      subsurface chemisorption of oxidants on compound semiconductor substrates can be
      detrimental, it has been shown theoretically and experimentally that oxidants are
      critical to removing metallic defects at oxide/compound semiconductor interfaces
      present in nanoscale channels, oxides, and other nanostructures. 

PMID- 25844579
TI  - Polyisobutylene-Based pH-Responsive Self-Healing Polymeric Gels.
AB  - This work demonstrates the successful application of dynamic covalent chemistry
      for the construction of self-healing gels from side-chain primary amine leucine
      pendant diblock copolymers of polyisobutylene (PIB) ((P(H2N-Leu-HEMA)-b-PIB)) in
      the presence of PIB based dialdehyde functionalized cross-linker (HOC-PIB-CHO)
      through imine (-HC?N-) bond formation without aiding any external stimuli. Gels
      were synthesized in 1,4-dioxane at room temperature at varied wt % of gelator
      concentration, [H2N]/[CHO] ratios and molecular weight of the block segments. The
      mechanical property of gels was examined by rheological measurements. We observed
      higher value of storage modulus (G') than the loss modulus (G") within the
      linearity limits of deformation, indicating the rheological behavior in the gel
      is dominated by an elastic property rather than a viscous property. The G' values
      significantly depend upon the extent of cross-linking in the gel network. To
      establish self-healing property of the gels, rheology analysis through step
      strain measurements (strain = 0.1 to 200%) at 25  degrees C was performed. The
      polymeric gel network shows reversible sol-gel transition for several cycles by
      adjusting the pH of the medium with the help of hydrochloric acid (HCl) and
      triethylamine (Et3N) triggers. FT-IR spectroscopy established formation of imine
      bonds in the gel network and these gels showed poor swelling behavior in various
      organic solvents because of the small interstitial porosity, confirmed by field
      emission-scanning electron microscopy (FE-SEM). 

PMID- 25844580
TI  - Impact of prenatal exposure to psychotropic drugs on neonatal outcome in infants
      of mothers with serious psychiatric illnesses.
AB  - OBJECTIVE: To assess whether prenatal exposure to 4 major classes of psychotropic
      drugs compared with no exposure differed with respect to neonatal outcome.
      METHOD: We used the database collected from 13 mother-baby units (MBUs) by the
      French Network of MBUs. The Marce Clinical Checklist was used to collect data
      from maternal interview and clinical record with respect to maternal demographic
      and clinical characteristics, prenatal exposure to psychotropic drugs, and
      neonatal outcome (birth weight, preterm birth, neonatal hospitalization).
      Multivariate logistic regression was used to explore the independent impact of
      each therapeutic class of psychotropic drug (antipsychotics, antidepressants,
      mood stabilizers, and anxiolytics/hypnotics) on infant outcomes. All the models
      were adjusted for maternal confounding factors. RESULTS: The sample included
      1,071 women and their infants. Nearly half (40.2%) used at least 1 psychotropic
      drug during pregnancy. The risk of low birth weight was increased by antenatal
      exposure to mood stabilizers (adjusted odds ratio [aOR] = 2.04, 95% confidence
      interval [CI] = 1.03-4.04, P = .04). The risk of neonatal hospitalization was
      increased by prenatal exposure to antipsychotics (aOR = 1.74, 95% CI = 1.19-2.54,
      P = .004), antidepressants (aOR = 1.59, 95% CI = 1.05-2.41, P = .03) or
      anxiolytics/hypnotics (aOR = 1.89, 95% CI = 1.30-2.75, P = .001), independent of
      birth weight and term delivery status. CONCLUSIONS: Infants exposed to
      psychotropic drugs during pregnancy have less optimal neonatal outcome than
      unexposed infants and should be considered as a high-risk population.

PMID- 25844581
TI  - N-heterocyclic carbene nitric oxide radicals.
AB  - N-Heterocyclic carbene-stabilized nitric oxide radicals were prepared by direct
      addition of nitric oxide to two N-heterocyclic carbenes in solution phase. The
      compounds were fully characterized by X-ray crystallography and EPR. The nitric
      oxide moiety in the solid compounds obtained can be thermally transferred to
      another N-heterocyclic carbene, suggesting potential applications to NO delivery.

PMID- 25844582
TI  - We can do better for our veterans' health care.

PMID- 25844583
TI  - Orthopedic registries: second thoughts.

PMID- 25844584
TI  - The value of national and hospital registries.

PMID- 25844585
TI  - Using wearable technology to record surgical videos.

PMID- 25844586
TI  - Arthroscopic anterior cruciate ligament reconstruction using a flexible guide pin
      with a rigid reamer.
AB  - Successful anterior cruciate ligament reconstruction depends heavily on accurate
      placement of the graft within the anatomical insertion of the native anterior
      cruciate ligament. Inaccurate placement can lead to graft failure and recurrent
      instability. Flexible guide pins and reamers have been developed to overcome some
      of the limitations of using transtibial and anteromedial portals to drill femoral
      tunnels. Early in our experience with flexible instruments, reamer breakage
      caused complications. We therefore developed a technique that uses a flexible
      guide pin with a rigid reamer to place the femoral tunnel in an anatomical
      position. This technique allows placement of longer anatomical tunnels through an
      anteromedial portal, reduces time spent with the knee in hyperflexion, provides
      better viewing, poses less risk of damage to the articular cartilage and
      neurovascular structures, and at a lower cost with less risk of reamer breakage.

PMID- 25844587
TI  - The importance of sex of patient in the management of femoroacetabular
      impingement.
AB  - Femoroacetabular impingement (FAI), a recently described hip condition in
      adolescents and young adults, typically manifests as activity-related hip pain.
      Characteristic physical findings include limited passive internal rotation of the
      affected hip and a positive impingement sign. Diagnostic imaging may reveal cam
      and/or pincer lesions, and associated intra-articular pathology (eg, labral tear,
      chondral damage) is common. When nonoperative treatment fails to adequately
      alleviate symptoms, surgery may be warranted. Both open and arthroscopic
      techniques have been effective. As our understanding of FAI continues to evolve,
      sex-based differences in incidence, presentation, and outcomes for patients with
      FAI have become apparent. Understanding the different ways in which males and
      females may present with FAI and then changing clinical practice patterns to
      accommodate these sexual dimorphisms will likely result in improved outcomes for
      each patient with symptomatic FAI. 

PMID- 25844588
TI  - In vitro and in situ characterization of arthroscopic loop security and knot
      security of braided polyblend sutures: a biomechanical study.
AB  - We conducted a study to evaluate biomechanical performance during destructive
      testing of several different suture materials in various arthroscopic knot
      configurations under both in vitro and in situ conditions. Surgeons of different
      levels of experience tied the knots. Three different arthroscopic knots (static
      surgeon's, Weston, Tennessee slider) with 3 reverse half-hitches on alternating
      posts were tested using Fiberwire, ForceFiber, Orthocord, and Ultrabraid suture
      materials under both in vitro and in situ (blood plasma at 37 degrees C)
      conditions. Three surgeons of different experience levels tied the knots on a
      post 30 mm in circumference. A single load-to-failure test was performed. There
      were no significant in vitro-in situ differences for Ultrabraid in the different
      knot configurations or with the different experience levels. Surgeon B
      (intermediate experience) showed no significant differences between test
      conditions for any knot configuration or suture material. With Tennessee slider
      knots, surgeon C (least experience) showed significantly lower clinical failure
      load under both test conditions and had a higher percentage of complete knot
      slippage. Surgeon B had no knot slippage with use of Fiberwire. Both the aqueous
      environment and the surgeon's familiarity with certain knots have an effect on
      knot security.

PMID- 25844589
TI  - Extensor pollicis longus ruptures in distal radius fractures: clinical and
      cadaveric studies with a new therapeutic intervention.
AB  - We conducted a study to evaluate aspiration of the third dorsal compartment as a
      therapeutic option for preventing extensor pollicis longus ruptures in
      association with distal radius fractures. A cadaveric model with a nondisplaced
      distal radius fracture was created, and radiopaque (Hypaque) dye was injected
      into the fracture site. Pressure readings were taken from the third dorsal
      compartment before and after dye injection. The compartment was aspirated with an
      18-gauge needle, and compartment pressures were measured again. There was a
      significant decrease in pressures after aspiration. Results in our cadaveric
      model were consistent with those in in vitro decompression of the third dorsal
      compartment. Clinical studies may determine that in-office needle aspiration is
      beneficial in preventing extensor pollicis longus rupture in nondisplaced distal
      radius fractures.

PMID- 25844590
TI  - Greater auricular nerve palsy after arthroscopic anterior-inferior and posterior
      inferior labral tear repair using beach-chair positioning and a standard
      universal headrest.
AB  - Shoulder arthroscopy is a common treatment for numerous different pathologies. An
      iatrogenic nerve injury that occurs during shoulder arthroscopy is more common
      than previously recognized. However, though many nerve pathologies are
      increasingly being recognized, reported cases of greater auricular nerve injury
      are limited. For instance, a case of greater auricular nerve palsy was reported
      in only 2 series that used a horseshoe headrest. One set of authors discontinued
      and recommended against use of this headrest, and the other recommended a
      headrest redesign. Here we report on a case of greater auricular nerve palsy that
      occurred after the patient's anterior-inferior and posterior-inferior labral tear
      was arthroscopically repaired using beach-chair positioning and a standard
      universal headrest. The palsy resulted in numbness and dysesthesia, which
      lessened gradually over 3 months after surgery and was completely resolved by 6
      months. 

PMID- 25844591
TI  - Lumbar degenerative disc disease and tibiotalar joint arthritis: a 710-specimen
      postmortem study.
AB  - Research has associated lumbar spinal disease with lower extremity arthrosis.
      These studies focused solely on the lumbar spine's connection with hip or knee
      pathology, failing to investigate potential ankle relationships. We specifically
      explored the interplay between lumbar disc degeneration and tibiotalar joint
      arthritis. Lumbar disc degeneration and tibiotalar joint arthritis was graded 0
      to 4, according to osteophytosis of the vertebral rim and talar surface in 710
      randomly selected cadaveric specimens. We corrected for confounding factors of
      age, sex, race, and height. A significant association was found between lumbar
      disc degeneration and tibiotalar joint arthritis (P < .01). Lumbar disc
      degeneration encompassing 3 intervetebral discs demonstrated the highest odds for
      development of severe tibiotalar joint arthritis. Severe lumbar degenerative disc
      disease was more prevalent than severe tibiotalar joint arthritis in individuals
      age 20 years and older. Furthermore, the presence of severe lumbar degeneration
      significantly predisposes individuals to the development of severe ankle
      arthritis (P < .05). Gait changes resulting from disc degeneration or neural
      compression in the lumbar spine may play a role in ankle osteoarthritis
      development. This association must be considered when treating patients with
      lumbar disc degeneration and leg pain.

PMID- 25844592
TI  - Comparison of locked plate fixation and nonoperative management for displaced
      proximal humerus fractures in elderly patients.
AB  - Use of locked plate fixation for proximal humerus fractures in elderly patients
      has increased markedly in recent years. We conducted a study to compare outcomes
      of operative (locked plate fixation) and nonoperative management of these
      fractures. From our database, we identified 207 displaced proximal humerus
      fractures that met all inclusion and exclusion criteria. For patients who
      accepted our invitation to return for evaluation, clinical outcome was assessed
      using several questionnaires: Constant; DASH (Disabilities of the Arm, Shoulder,
      and Hand); SMFA (Short Musculoskeletal Functional Assessment); and Patient
      Reported Outcomes Measurement Information System (PROMIS) Physical Function
      Computer Adaptive Test. Of the 207 patients, 61 were managed operatively and 146
      nonoperatively. Operative patients had lower rates of malunion but higher rates
      of complications, which included screw perforation, loss of fixation, infection,
      and secondary surgical procedures. Forty-seven patients (a mix of operative and
      nonoperative) accepted our invitation to return for clinical evaluation at a mean
      follow-up of 3.3 years. The 2 groups' clinical outcomes were similar.

PMID- 25844593
TI  - Massive baker cyst resulting in tibial nerve compression neuropathy secondary to
      polyethylene wear disease.
AB  - Symptomatic synovial cyst formation is an infrequent, late complication after
      total knee arthroplasty. Most often, these cysts are found incidentally. However,
      rarely they may become larger leading to significant pain and disability. The
      formation of gigantic cysts necessitating revision knee surgery has been detailed
      in a few case reports. To the author's knowledge, this is the first report in the
      medical literature that describes peripheral neuropathy of the tibial nerve
      secondary to a massive Baker cyst after total knee replacement. 

PMID- 25844594
TI  - Failure of artelon interposition arthroplasty after partial trapeziectomy: a case
      report with histologic and immunohistochemical analysis.
AB  - Artelon is a degradable biomaterial used for the treatment of osteoarthritis in
      the carpometacarpal joint of the thumb. The device reportedly works through 2
      modes of action-stabilization of the carpometacarpal joint by augmentation of the
      joint capsule and by formation of a new articular surface at the
      trapeziometacarpal interface. We present a patient with late failure of
      arthroscopic hemitrapeziectomy and Artelon interposition that required surgical
      excision of the Artelon implant and trapeziectomy 4 years postoperatively. Gross
      and histologic evaluation of the explanted Artelon implant and remaining
      trapezium revealed lack of articular resurfacing by hyaline ingrowth.

PMID- 25844595
TI  - Successful surgical treatment of an intraneural ganglion of the common peroneal
      nerve.
AB  - Intraneural ganglion cysts of peripheral nerves occurring within the epineural
      sheath are rare, and their mechanism of formation and treatment options are
      debated. We present a case of a 41-year-old man who presented with a complaint of
      lateral-sided left knee pain with numbness on the lateral side of the foot who
      was diagnosed with an intraneural ganglion of the common peroneal nerve (CPN). He
      was treated initially with common peroneal epineural decompression only to have
      symptoms recur 6 weeks postoperatively. The patient was subsequently treated
      utilizing the suggestions of the "unified articular theory," which proposes a
      small recurrent articular branch of the CPN as the source of cyst fluid. This
      branch was surgically detached, leading to complete alleviation of his symptoms.
      When the patient was reevaluated 2 years postoperatively, his preoperative
      symptoms had resolved, and a follow-up magnetic resonance image showed resolution
      of the enlargement of the CPN.

PMID- 25844596
TI  - Revision anterior cruciate ligament reconstruction with bone-patellar tendon-bone
      allograft and extra-articular iliotibial band tenodesis.
AB  - Revision anterior cruciate ligament (ACL) reconstruction is a technically
      demanding procedure with outcomes that generally fail to reach those seen with
      primary ACL reconstruction. With most index procedures using autograft tissue, it
      is not uncommon for allograft tissue to be required for revision ACL
      reconstruction. Compared with autografts, allografts take longer to incorporate
      and lead to more episodes of instability. In this article, we describe
      ipsilateral iliotibial band tenodesis performed to augment use of bone-patellar
      tendon-bone allograft in revision ACL reconstruction. This technique adds
      rotational stability to protect the allograft tissue while it incorporates.

PMID- 25844597
TI  - A systematic review of tibialis anterior tendon rupture treatments and outcomes.
AB  - Tibialis anterior (TA) tendon rupture is a relatively rare injury that has been
      documented primarily in case reports. This article is the first large systematic
      review of the literature on treatment techniques for subcutaneous rupture of TA
      tendons. Studies for review were identified through a PubMed search. Eligible
      studies involved cases of closed tendon rupture. Of the 87 cases in the study, 72
      were treated with surgery, 15 with conservative measures. Mean age was 63.9 years
      (surgery group) and 72.4 years (conservative treatment group). Primary repair was
      used most often for newer injuries, autograft most often for older injuries.
      Operative repair of subcutaneous TA tendon rupture leads to successful outcomes
      in many patients. A surgeon who is deciding which operative technique to use for
      a patient should consider the age of the injury and the findings of
      intraoperative assessment for tendon necrosis.

PMID- 25844598
TI  - Superior Conductive Solid-like Electrolytes: Nanoconfining Liquids within the
      Hollow Structures.
AB  - The growth and proliferation of lithium (Li) dendrites during cell recharge are
      currently unavoidable, which seriously hinders the development and application of
      rechargeable Li metal batteries. Solid electrolytes with robust mechanical
      modulus are regarded as a promising approach to overcome the dendrite problems.
      However, their room-temperature ionic conductivities are usually too low to reach
      the level required for normal battery operation. Here, a class of novel solid
      electrolytes with liquid-like room-temperature ionic conductivities (>1 mS cm(
      1)) has been successfully synthesized by taking advantage of the unique
      nanoarchitectures of hollow silica (HS) spheres to confine liquid electrolytes in
      hollow space to afford high conductivities (2.5 mS cm(-1)). In a symmetric
      lithium/lithium cell, the solid-like electrolytes demonstrate a robust
      performance against the Li dendrite problem, preventing the cell from short
      circuiting at current densities ranging from 0.16 to 0.32 mA cm(-2) over an
      extended period of time. Moreover, the high flexibility and compatibility of HS
      nanoarchitectures, in principle, enables broad tunability to choose desired
      liquids for the fabrication of other kinds of solid-like electrolytes, such as
      those containing Na(+), Mg(2+), or Al(3+) as conductive media, providing a useful
      alternative strategy for the development of next generation rechargeable
      batteries. 

PMID- 25844600
TI  - Pre-clinical evaluation of the MDM2-p53 antagonist RG7388 alone and in
      combination with chemotherapy in neuroblastoma.
AB  - Neuroblastoma is a predominantly p53 wild-type (wt) tumour and MDM2-p53
      antagonists offer a novel therapeutic strategy for neuroblastoma patients. RG7388
      (Roche) is currently undergoing early phase clinical evaluation in adults. This
      study assessed the efficacy of RG7388 as a single-agent and in combination with
      chemotherapies currently used to treat neuroblastoma in a panel of neuroblastoma
      cell lines. RG7388 GI50 concentrations were determined in 21 p53-wt and mutant
      neuroblastoma cell lines of varying MYCN, MDM2 and p14(ARF) status, together with
      MYCN-regulatable Tet21N cells. The primary determinant of response was the
      presence of wt p53, and overall there was a >200-fold difference in RG7388 GI50
      concentrations for p53-wt versus mutant cell lines. Tet21N MYCN+ cells were
      significantly more sensitive to RG7388 compared with MYCN- cells. Using median
      effect analysis in 5 p53-wt neuroblastoma cell lines, selected combinations of
      RG7388 with cisplatin, doxorubicin, topotecan, temozolomide and busulfan were
      synergistic. Furthermore, combination treatments led to increased apoptosis, as
      evident by higher caspase-3/7 activity compared to either agent alone. These data
      show that RG7388 is highly potent against p53-wt neuroblastoma cells, and
      strongly supports its further evaluation as a novel therapy for patients with
      high-risk neuroblastoma and wt p53 to potentially improve survival and/or reduce
      toxicity.

PMID- 25844599
TI  - Molecular profiling of prostate cancer derived exosomes may reveal a predictive
      signature for response to docetaxel.
AB  - Docetaxel is a cornerstone treatment for metastatic, castration resistant
      prostate cancer (CRPC) which remains a leading cause of cancer-related deaths,
      worldwide. The clinical usage of docetaxel has resulted in modest gains in
      survival, primarily due to the development of resistance. There are currently no
      clinical biomarkers available that predict whether a CRPC patient will respond or
      acquire resistance to this therapy. Comparative proteomics analysis of exosomes
      secreted from DU145 prostate cancer cells that are sensitive (DU145 Tax-Sen) or
      have acquired resistance (DU145 Tax-Res) to docetaxel, demonstrated significant
      differences in the amount of exosomes secreted and in their molecular
      composition. A panel of proteins was identified by proteomics to be
      differentially enriched in DU145 Tax-Res compared to DU145 Tax-Sen exosomes and
      was validated by western blotting. Importantly, we identified MDR-1, MDR-3,
      Endophilin-A2 and PABP4 that were enriched only in DU145 Tax-Res exosomes. We
      validated the presence of these proteins in the serum of a small cohort of
      patients. DU145 cells that have uptaken DU145 Tax-Res exosomes show properties of
      increased matrix degradation. In summary, exosomes derived from DU145 Tax-Res
      cells may be a valuable source of biomarkers for response to therapy. 

PMID- 25844601
TI  - Aquaporin 1 and 5 expression decreases during human intervertebral disc
      degeneration: Novel HIF-1-mediated regulation of aquaporins in NP cells.
AB  - Objectives of this study were to investigate whether AQP1 and AQP5 expression is
      altered during intervertebral disc degeneration and if hypoxia and HIF-1 regulate
      their expression in NP cells. AQP expression was measured in human tissues from
      different degenerative grades; regulation by hypoxia and HIF-1 was studied using
      promoter analysis and gain- and loss-of-function experiments. We show that both
      AQPs are expressed in the disc and that mRNA and protein levels decline with
      human disease severity. Bioinformatic analyses of AQP promoters showed multiple
      evolutionarily conserved HREs. Surprisingly, hypoxia failed to induce promoter
      activity or expression of either AQP. While genomic chromatin immunoprecipitation
      showed limited binding of HIF-1alpha to conserved HREs, their mutation did not
      suppress promoter activities. Stable HIF-1alpha suppression significantly
      decreased mRNA and protein levels of both AQPs, but HIF-1alpha failed to induce
      AQP levels following accumulation. Together, our results demonstrate that AQP1
      and AQP5 expression is sensitive to human disc degeneration and that HIF-1alpha
      uniquely maintains basal expression of both AQPs in NP cells, independent of
      oxemic tension and HIF-1 binding to promoter HREs. Diminished HIF-1 activity
      during degeneration may suppress AQP levels in NP cells, compromising their
      ability to respond to extracellular osmolarity changes. 

PMID- 25844602
TI  - miR-942 promotes cancer stem cell-like traits in esophageal squamous cell
      carcinoma through activation of Wnt/beta-catenin signalling pathway.
AB  - The Wnt/beta-catenin signalling pathway is known to play a vital role in the
      maintenance of cancer stem cells (CSCs), which are reported to be the origin of
      malignant cancers, and result in poor prognosis of multiple kinds of cancer.
      Therefore, it is of great importance to illuminate the mechanism by which the
      Wnt/beta-catenin pathway regulates the cancer stem cell-like traits in cancers.
      Here, we report that miR-942 is significantly upregulated in esophageal squamous
      cell carcinoma (ESCC), and miR-942 levels are associated with poor prognosis in
      ESCC patients. Overexpression of miR-942 promotes, whereas inhibition of miR-942
      decreases, the tumor sphere formation, the CD90+ subpopulation cells and the
      expression of pluripotency associated markers. Moreover, in vivo assay shows that
      miR-942 overexpressing cells form larger tumors and display higher
      tumourigenesis. Furthermore, we demonstrate that miR-942 upregulates the Wnt/beta
      catenin signaling activity via directly targeting sFRP4, GSK3beta and TLE1, which
      are multiple level negative regulators of the Wnt/beta-catenin signaling cascade.
      In addition, our results indicate that c-myc directly binds to the miR-942
      promoter and promotes its expression. Taken together, our findings establish an
      oncogenic role of miR-942 in ESCC and indicate that miR-942 might be an effective
      therapeutic target for ESCC.

PMID- 25844604
TI  - Treatment of chronic spontaneous urticaria.

PMID- 25844605
TI  - Pollution as a risk factor for the development of melasma and other skin
      disorders of facial hyperpigmentation - is there a case to be made?
AB  - Worldwide air pollution is a major health concern. There is accumulating
      scientific evidence that air pollution plays an important role in extrinsic
      aging. This article invites the reader to consider pollution as a possible
      emerging etiologic agent for the development of melasma. Pollution may be a risk
      factor for melasma and other facial pigmentary dyschromias. Air pollution in the
      form of airborne particulate matter (PM) and Polycyclic aromatic hydrocarbons
      (PAHs) enter the skin via nanoparticles and generate quinones, which are redox
      cycling chemicals that produce reactive oxygen species (ROS). The PM increases
      the amount of ROS that triggers the increase of metalloproteinases that leads to
      extrinsic aging, which includes skin pigmentation. The incidence of disorders of
      facial hyperpigmentation specifically, melasma, is increased in persons of skin
      type III-VI living in India and South East Asia. Interestingly, these are also
      geographic regions with very heavy pollution. India, South East Asia, China, and
      United States lead the world in air pollution.

PMID- 25844606
TI  - Cutaneous lupus erythematosus in skin of color.
AB  - Cutaneous Lupus Erythematosus (CLE) is a common manifestation in patients with
      Systemic Lupus Erythematosus. In a significant population of patients, CLE is the
      predominant feature and, in some cases, patients suffer from cutaneous disease
      alone. Chronic Cutaneous Lupus Erythematosus (CCLE) is a scarring subtype, more
      prevalent in blacks. Patients with skin of color may pose a challenge to
      physicians due to exaggerated cutaneous findings and increased risk of post
      inflammatory hyperpigmentation and hypertrophic scarring. With the demographics
      of the United States rapidly shifting towards a greater population of non
      Caucasian racial and ethnic groups, it is imperative that we expand on the
      limited research into molecular variation, clinical presentation, and therapeutic
      efficacy in CLE. The purpose of this review is to bring attention to the unique
      and severe aspects of CLE in persons of color, which calls for early and
      aggressive treatment.

PMID- 25844603
TI  - Rejuvenating immunity: "anti-aging drug today" eight years later.
AB  - The 2014 year ended with celebration: Everolimus, a rapamycin analog, was shown
      to improve immunity in old humans, heralding "a turning point" in research and
      new era in human quest for immortality. Yet, this turning point was predicted a
      decade ago. But what will cause human death, when aging will be abolished? 

PMID- 25844607
TI  - Efficacy and safety of incobotulinumtoxin A for the correction of glabellar lines
      among patients with skin types IV to VI.
AB  - BACKGROUND: Despite the frequent use of botulinumtoxin A (BoNTA) in non-Caucasian
      patients, safety and efficacy has not been well characterized in persons with
      darker skin. OBJECTIVE: To investigate the efficacy and safety of
      incobotulinumtoxin A [Xeomin(r) (XEO)] for the correction of glabellar lines
      among non-Caucasian patients with Fitzpatrick skin types IV to VI. METHODS: This
      open-label, single-center, post-marketing study treated 29 patients with
      Fitzpatrick skin types IV to VI with moderate to severe glabellar frown lines.
      Evaluation at day 0 included standardized photographs and patient and
      investigator assessments. Post evaluation, XEO was administered at 5
      intramuscular injection sites with equal aliquots of 4 units per 0.1 mL.
      Photographs and assessments were repeated at days 30 and 90. RESULTS: Response to
      treatment was defined as a 1 or more point improvement in patient and
      investigator assessments. At day 30, 100% (n = 29; 95 C.I. 0.87, 1.00; P< .001)
      responded to treatment. At day 90, 69% (n=20; 95% C.I. 0.52, 0.83; P= .42)
      responded to treatment. The safety profile was similar to previously reported
      trials with BoNTA. CONCLUSION: The efficacy and safety of XEO among patients with
      skin types IV to VI is similar to that among persons with fairer skin.

PMID- 25844608
TI  - Evaluation of benefit to educational material for photoprotection in those with
      cutaneous lupus erythematosus.
AB  - BACKGROUND: Photosensitivity (PS) in cutaneous lupus erythematosus (CLE)
      contributes to decreased quality of life (QoL). AIMS: We aimed to assess baseline
      knowledge about sun protection in persons with CLE and identify knowledge
      differences by race. Additionally, we aimed to determine the impact of a verbal
      educational intervention on photoprotection and CLE. METHODS: 31 adults with CLE
      were recruited from an academic-based dermatology clinic and completed a 17-item
      questionnaire about CLE and sun protection at three time points: pre-
      intervention (PR-I), post-intervention (PO-I), and 3-month phone follow up (3MF).
      An educational intervention using American Academy of Dermatology CLE and sun
      protection education materials was delivered between PR-I and PO-I. RESULTS: 31
      subjects participated at PR-I and PO-I, and 25 subjects (81%) at 3MF. Baseline
      CLE-related PS and photoprotection knowledge differed significantly by race, with
      non-Caucasians demonstrating less knowledge (P= 0.049). Knowledge about sun
      exposure being linked to lupus increased from 81% to 97% (P=0.25) between PR-I
      and PO-I. At PR-I, 19% agreed that smoking was linked to lupus compared to 90% PO
      I (P<0.001). There was increased knowledge of lupus risk for non-Caucasians, UV
      exposure indoors, and photo-avoidance during peak daytime (P<0.001). CONCLUSION:
      There is a baseline disparity in knowledge related to PS and photo protection in
      CLE by race. A short educational intervention successfully improved immediate
      lupus-related PS and sun exposure knowledge, but knowledge was not retained long
      term. It appears educational materials must be improved.

PMID- 25844609
TI  - Study of human leukocyte antigen-cw in Egyptian patients with vitiligo.
AB  - Human leukocyte antigen (HLA) antigens vary considerably in different racial
      groups, and an analysis of results from several geographical locations suggests
      that vitiligo appears to be associated with different HLA antigens in different
      groups. The aim of this work was to assess the association of HLA-Cw with
      vitiligo in the Egyptian population. Forty unrelated patients with nonsegmental
      vitiligo and 20 matched controls were selected. A polymerase chain reaction
      sequence specific primer (PCR-SSP) method was used to determine HLA DNA typing.
      There was a statistically significant difference in the association of HLA-Cw6
      with vitiligo in the 2 studied groups. A comparatively increased number of
      patients showed HLA-Cw2 and HLA-Cw7 (13.64%). However, there were no
      statistically significant differences. To the best of our knowledge, this is the
      first molecular study of HLA typing in Egyptian patients with vitiligo. Our
      findings are in agreement with earlier studies that reported statistically
      increased frequencies for allele of HLA-Cw6 in Northern Italian, Kuwaiti, Chinese
      Han, and Saudi populations (45.45%, P<.05).

PMID- 25844610
TI  - Quantifying the impact cosmetic make-up has on age perception and the first
      impression projected.
AB  - INTRODUCTION: First impressions are lasting, consequential and defined as the
      immediate judgment made of another from zero acquaintance. Multiple studies have
      reported the benefits of cosmetic make-up. We set out to investigate the
      psychosocial and aesthetic effects of cosmetic make-up in order to better
      understand why women wear it. MATERIALS AND METHODS: Twenty-seven women were
      recruited in order to examine the effects of cosmetic make-up on first
      impressions. The photographs of individual subjects wearing the control
      cosmetics, their own make-up, and no make-up were randomly assigned to three
      binders (A, B, and C). Three hundred evaluators participated (100 evaluators per
      book) and completed a 10-point First Impression Scale for each of the 27 photos
      in their binder. RESULTS: Statistical analysis of the collected data was
      conducted in SPSS using two-tailed t-tests to determine the statistical
      significance of the differences between first impressions of Own Make-up vs No
      Make-up, No Make-up vs Control Make-up, and Own Makeup vs Control Make-up. There
      was a significant difference in improvement in all pairings across all 8
      categories in the First Impressions questionnaire particularly in perceived age
      between own make-up, no make-up, control make-up (41, 42, 38; P<0.001).
      DISCUSSION: Our study evaluated the first impressions, age perception, self
      esteem, and the quality of life impact that cosmetic makeup has on women's
      appearance and confidence. Subjects wearing cosmetic make-up appeared 4 years
      younger than those wearing no make-up. And the control cosmetic make-up subjects
      on average projected a 37% better first impression than subjects wearing no make
      up. We objectively quantified and qualified the benefits of applying cosmetic
      make-up. Make-up can reduce the perceived age, improve the first impression
      projected and increase the self-esteem of those who apply it.

PMID- 25844611
TI  - A novel patient support program to address isotretinoin adherence: proof-of
      concept analysis.
AB  - The iPLEDGE protocol for isotretinoin treatment requires multiple steps to be
      completed within strict timing windows, resulting in many interruptions or
      discontinuations of treatment. The US Food and Drug Administration has indicated
      that approximately 40% of isotretinoin prescriptions written over the course of
      one year of the iPLEDGE program were denied due to failure to comply with
      iPLEDGE. Insurance restrictions add to the likelihood of prescriptions not being
      filled. Here, we describe a novel program implemented specifically to assist
      patients and providers with improving isotretinoin therapy adherence. This
      innovative isotretinoin support program provides assistance with insurance
      questions and hurdles, an uninterrupted treatment supply, educational support,
      reminder communications, and an indigent patient assistance program. Proof-of
      concept analysis shows that 17 months after implementation of the program, 93% of
      prescriptions received have been filled. Utilization of the program appears to
      improve adherence to an isotretinoin treatment regimen, with fewer interruptions
      due directly to unfilled prescriptions.

PMID- 25844612
TI  - The efficacy and tolerability of a fixed combination clindamycin (1.2%) and
      benzoyl peroxide (3.75%) aqueous gel in patients with facial acne vulgaris:
      gender as a clinically relevant outcome variable.
AB  - OBJECTIVE: To investigate whether treatment differences exist in male and female
      patients with moderate to severe acne treated with clindamycin phosphate 1.2%/BP
      3.75% gel or vehicle as monotherapy. METHODS: A post hoc analysis comparing the
      efficacy and cutaneous tolerability in 498 male and female patients with moderate
      to severe acne receiving clindamycin phosphate 1.2%/BP 3.75% gel, or vehicle for
      12 weeks. RESULTS: The efficacy of clindamycin phosphate 1.2%/BP 3.75% gel was
      greater than vehicle (P>.001) in both genders. Within the clindamycin phosphate
      1.2%/BP 3.75% gel group, the mean percent change from baseline in inflammatory
      and noninflammatory lesion counts was greater among females than males, as was
      the percentage of subjects who achieved a 2-grade reduction in the EGSS (P=.049).
      LIMITATIONS: It is not possible to determine the contributions of the individual
      active ingredients. CONCLUSIONS: Clindamycin phosphate 1.2%/BP 3.75% gel provides
      statistically significant greater efficacy than vehicle with a favorable safety
      and tolerability profile. It appears to be more effective in female patients.

PMID- 25844613
TI  - A method for maintaining the clinical results of 4% hydroquinone and 0.025%
      tretinoin with a cosmeceutical formulation.
AB  - Facial dyspigmentation treatment is an unmet need in dermatology with increasing
      challenges due to the questionable safety of hydroquinone. This research examined
      a new OTC formulation containing hydroxyphenoxy propionic acid, ellagic acid,
      yeast extract, and salicylic acid on subjects who previously completed 12 weeks
      of treatment with 4% hydroquinone and 0.025% retinoic acid. The goal of this
      study was to evaluate the skin lightening and tolerability profile of a 20-week
      maintanence therapy with a cosmeceutical formulation during the summer months. 33
      healthy subjects ages 25-60 years with moderate facial dyspigmentation defined as
      a score of 3 on a 5-point scale were enrolled. There was statistically
      significant improvement at week 20 in terms of even skin tone (P<0.001), spot
      intensity (P<0.001), spot size (P<0.05) and overall hyperpigmentation (P>=0.002).

PMID- 25844614
TI  - Evaluation of a novel home skin care platform.
AB  - The home beauty device market is rapidly growing, having more than tripled in the
      last four years. This study evaluates several specific attachment heads using a
      novel home skincare platform (HSP). By incorporating multiple treatment heads for
      cleansing, skin smoothing, and skin infusion, this device has the potential to
      address many potential treatment goals. The first subset of this study is a
      blinded, randomized split-face study evaluating the efficacy of the HSP device
      with a standard brush head for make-up removal and compares the HSP device to a
      currently marketed home cleansing device. The results show that the HSP cleansing
      head was comparable to the leading home skin cleansing device on the market. The
      HSP's skin smoothing head showed statistically significant improvement in
      erythema and dryness over baseline levels with significant histologic changes
      including normalization of epidermal thickness in only 10 days of use. This is
      comparable to and exceeds many well-studied antiaging treatments after weeks and
      months of therapy. Finally, the infusion head demonstrated improvement in skin
      hydration over baseline levels.

PMID- 25844615
TI  - Assessment of the safety and efficacy of topical copper chlorophyllin in women
      with photodamaged facial skin.
AB  - BACKGROUND: Chronic exposure to the sun causes the skin to prematurely age.
      Photodamaged skin is characterized by progressive damage to the dermal
      extracellular matrix with loss of collagen and degradation of elastin. Clinical
      manifestations of such photoaged or photodamaged skin include wrinkles and
      irregular pigmentation. Various cosmetic treatments including topical retinoids,
      growth factors, and skin lighteners have shown some benefit. Salts of copper
      chlorophyllin complex are semi-synthetic naturally derived compounds with anti
      oxidant and wound healing activity that has not been previously tested in
      photodamaged skin. OBJECTIVES: This single-center pilot study was conducted to
      assess the efficacy and safety of a liposomal dispersion of topically applied
      sodium copper chlorophyllin complex in women with mild-moderate fine lines and
      wrinkles in the periocular areas and facial solar lentigenes over a course of 8
      weeks. METHODS: Subjects were supplied with the test product, a topical gel
      containing chlorophyllin complex salts (0.066%), with directions to apply a pea
      sized amount to the periocular areas, cheeks and nose every morning and evening.
      Clinical assessments were performed at screening/baseline and at week 8.
      Standardized digital photographs were taken and self-assessment questionnaires
      were conducted. RESULTS: Ten subjects completed the 8-week study. All clinical
      efficacy parameters showed statistically significant improvements over baseline
      at week 8. The study product was well tolerated. Subject questionnaires showed
      the test product was highly rated. CONCLUSIONS: In this pilot study, a topical
      formulation containing a liposomal dispersion of sodium copper chlorophyllin
      complex was shown to be clinically effective and well tolerated for the treatment
      of mild-moderate photodamage and solar lentigenes when used for 8 weeks.

PMID- 25844616
TI  - Reduced appearance of under-eye bags with twice-daily application of epidermal
      growth factor (EGF) serum: a pilot study.
AB  - BACKGROUND: Under-eye bags are a common manifestation of age and a frequent
      complaint among patients who no longer feel youthful. Non-invasive topical agents
      are largely ineffective at reducing their appearance. OBJECTIVE: We studied the
      ability of a topical serum containing epidermal growth factor (EGF) to minimize
      the appearance of under-eye bags. METHODS: A single-center clinical trial was
      performed on eighteen volunteer male and female patients with under-eye bags.
      Subjects applied EGF serum to the infraorbital area twice daily for 12 weeks. At
      each visit, subjects were evaluated using clinical photography and written self
      assessment. A grade on the Merz Infraorbital Hollowness Scale was also given and
      two independent, blind investigators assigned an Investigator's Global Assessment
      (IGA) score. At the trial's end, patients shared their final evaluation and
      perception of results with a questionnaire. RESULTS: Sixteen subjects completed
      the trial. The final average Merz grade was 1.63 (SEM = .273), statistically
      significantly lower than the mean baseline average of 2.06 (SEM = .232) (P =
      .0019). A reduction in average IGA score was also significant (P< .0001). Average
      initial IGA was 2.75 (SEM = .270) and average final IGA was 2.00 (SEM = .310).
      All but two subjects reported improvement at the final visit. Improvement was
      quantified as 76-100% by two subjects, 50-75% by three subjects, and 25-49% by
      nine subjects. Eleven subjects classified their under-eye bags as milder at the
      end of the trial compared to the first visit. Seven subjects reported greater
      satisfaction with their overall facial appearance. Of the subjects who had used
      other topical treatments in the past, two reported the serum to be "significantly
      better" and four said it was "better" in treating their under-eye bags.
      CONCLUSION: Our results offer evidence that topical EGF can reduce the appearance
      of under-eye bags.

PMID- 25844617
TI  - Minocycline pigmentation following carbon dioxide laser resurfacing: treatment
      with the Q-switched Nd:YAG laser.
AB  - Minocycline is among the most common drugs to cause drug-induced pigmentation.
      Dermal deposition of drug metabolites typically occurs in areas of vascular
      leakage, such as surrounding lower extremity spider veins, within erythema
      associated with solar elastosis, and in areas of bruising. The skin affected by
      minocycline pigmentation typically takes on a slate-gray coloring in affected
      areas. The current patient developed minocycline pigmentation after carbon
      dioxide laser resurfacing of her upper lip to treat rhytides in the laser-treated
      area. Laser treatment with the 1,064 nm, Q-switched Nd:YAG laser was able to
      remove the pigmentation.

PMID- 25844618
TI  - IL-17A Is Elevated in End-Stage Chronic Obstructive Pulmonary Disease and
      Contributes to Cigarette Smoke-induced Lymphoid Neogenesis.
AB  - RATIONALE: End-stage chronic obstructive pulmonary disease (COPD) is associated
      with an accumulation of pulmonary lymphoid follicles. IL-17A is implicated in
      COPD and pulmonary lymphoid neogenesis in response to microbial stimuli. We
      hypothesized that IL-17A is increased in peripheral lung tissue during end-stage
      COPD and also directly contributes to cigarette smoke-induced lymphoid
      neogenesis. OBJECTIVES: To characterize the tissue expression and functional role
      of IL-17A in end-stage COPD. METHODS: Automated immune detection of IL-17A and IL
      17F was performed in lung tissue specimens collected from patients with Global
      Initiative for Chronic Obstructive Lung Disease stage I-IV COPD, and smoking and
      never-smoking control subjects. In parallel, Il17a(-/-) mice and wild-type
      control animals were exposed to cigarette smoke for 24 weeks, and pulmonary
      lymphoid neogenesis was assessed. MEASUREMENTS AND MAIN RESULTS: Tissue
      expression of IL-17A and IL-17F was increased in COPD and correlated with lung
      function decline. IL-17A was significantly elevated in severe to very severe COPD
      (Global Initiative for Chronic Obstructive Lung Disease III/IV) compared with
      both smokers and never-smokers without COPD. Although CD3(+) T cells expressed IL
      17A in very severe COPD, most IL-17A(+) cells were identified as tryptase
      positive mast cells. Attenuated lymphoid neogenesis and reduced expression of the
      B-cell attracting chemokine C-X-C motif ligand (CXCL) 12 was observed in
      cigarette smoke-exposed Il17a(-/-) mice. CXCL12 was also highly expressed in
      lymphoid follicles in COPD lungs, and the pulmonary expression was significantly
      elevated in end-stage COPD. CONCLUSIONS: IL-17A in the peripheral lung of
      patients with severe to very severe COPD may contribute to disease progression
      and development of lymphoid follicles via activation of CXCL12.

PMID- 25844619
TI  - The Effect of a Whey Protein Supplement on Bone Mass in Older Caucasian Adults.
AB  - CONTEXT: It has been assumed that the increase in urine calcium (Ca) that
      accompanies an increase in dietary protein was due to increased bone resorption.
      However, studies using stable Ca isotopes have found that dietary protein
      increases Ca absorption without increasing bone resorption. OBJECTIVE: The
      objective of the study was to investigate the impact of a moderately high protein
      diet on bone mineral density (BMD). DESIGN: This was a randomized, double-blind,
      placebo-controlled trial of protein supplementation daily for 18 months. SETTING:
      The study was conducted at two institutional research centers. PARTICIPANTS: Two
      hundred eight older women and men with a body mass index between 19 and 32
      kg/m(2) and a self-reported protein intake between 0.6 and 1.0 g/kg participated
      in the study. INTERVENTION: Subjects were asked to incorporate either a 45-g whey
      protein or isocaloric maltodextrin supplement into their usual diet for 18
      months. MAIN OUTCOME MEASURE: BMD by dual-energy x-ray absorptiometry, body
      composition, and markers of skeletal and mineral metabolism were measured at
      baseline and at 9 and 18 months. RESULTS: There were no significant differences
      between groups for changes in L-spine BMD (primary outcome) or the other skeletal
      sites of interest. Truncal lean mass was significantly higher in the protein
      group at 18 months (P = .048). C-terminal telopeptide (P = .0414), IGF-1 (P =
      .0054), and urinary urea (P < .001) were also higher in the protein group at the
      end of the study period. There was no difference in estimated glomerular
      filtration rate at 18 months. CONCLUSION: Our data suggest that protein
      supplementation above the recommended dietary allowance (0.8 g/kg) may preserve
      fat-free mass without adversely affecting skeletal health or renal function in
      healthy older adults.

PMID- 25844621
TI  - Correction to Survey of polyphenol constituents in grapes and grape-derived
      products.

PMID- 25844620
TI  - Adrenal Insufficiency in Corticosteroids Use: Systematic Review and Meta
      Analysis.
AB  - OBJECTIVE: We aimed to estimate pooled percentages of patients with adrenal
      insufficiency after treatment with corticosteroids for various conditions in a
      meta-analysis. Secondly, we aimed to stratify the results by route of
      administration, disease, treatment dose, and duration. METHODS: We searched seven
      electronic databases (PubMed, MEDLINE, EMBASE, COCHRANE, CENTRAL, Web of Science,
      and CINAHL/Academic Search Premier) in February 2014 to identify potentially
      relevant studies. Original articles testing adult corticosteroid users for
      adrenal insufficiency were eligible. RESULTS: We included 74 articles with a
      total of 3753 participants. Stratified by administration form, percentages of
      patients with adrenal insufficiency ranged from 4.2% for nasal administration
      (95% confidence interval [CI], 0.5-28.9) to 52.2% for intra-articular
      administration (95% CI, 40.5-63.6). Stratified by disease, percentages ranged
      from 6.8% for asthma with inhalation corticosteroids only (95% CI, 3.8-12.0) to
      60.0% for hematological malignancies (95% CI, 38.0-78.6). The risk also varied
      according to dose from 2.4% (95% CI, 0.6-9.3) (low dose) to 21.5% (95% CI, 12.0
      35.5) (high dose), and according to treatment duration from 1.4% (95% CI, 0.3
      7.4) (<28 d) to 27.4% (95% CI, 17.7-39.8) (>1 year) in asthma patients.
      CONCLUSIONS: 1) Adrenal insufficiency after discontinuation of glucocorticoid
      occurs frequently; 2) there is no administration form, dosing, treatment
      duration, or underlying disease for which adrenal insufficiency can be excluded
      with certainty, although higher dose and longer use give the highest risk; 3) the
      threshold to test corticosteroid users for adrenal insufficiency should be low in
      clinical practice, especially for those patients with nonspecific symptoms after
      cessation.

PMID- 25844622
TI  - Object-based attention in real-world scenes.
AB  - We are continually confronted with more visual information than we can process in
      a given moment. In order to interact effectively with our environment,
      attentional mechanisms are used to select subsets of environmental properties for
      enhanced processing. Previous research demonstrated that spatial regions can be
      selected based on either their low-level feature or high-level semantic
      properties. However, the efficiency with which we interact with the world
      suggests that there must be an additional, midlevel, factor constraining
      effective attentional space. The present study investigates whether object-based
      attentional selection is one such midlevel factor that constrains visual
      attention in complex, real-world scenes. Participants viewed scene images while
      their eye movements were recorded. During viewing, a cue appeared on an object
      which participants were instructed to fixate. A target then appeared either on
      the same object as the cue, on a different object, or floating. Participants
      initiated saccades faster and had shorter response times to targets presented on
      the same object as the fixated cue. The results strongly suggest that when
      attending to a location on an object, the entire object benefits perceptually.
      This object-based effect on the distribution of spatial attention forms a
      critical link between low- and high-level factors that direct attention
      efficiently in complex real-world scenes.

PMID- 25844623
TI  - A change of task prolongs early processes: evidence from ERPs in lexical tasks.
AB  - Switching tasks costs time. Allowing time to prepare reduces the cost, but
      usually leaves an irreducible "residual cost." Most accounts of this residual
      cost locate it within the response-selection stage of processing. To determine
      which processing stage is affected, we measured event-related potentials (ERPs)
      as participants performed a reading task or a perceptual judgment task, and
      examined the effect of a task switch on early markers of lexical processing. A
      task cue preceding a string of blue and red letters instructed the participant
      either to read the letter string (for a semantic classification in Experiment 1,
      and a lexical decision in Experiment 2) or to judge the symmetry of its color
      pattern. In Experiment 1, having to switch to the reading task delayed the
      evolution of the effect of word frequency on the reading task ERP by a
      substantial fraction of the effect on reaction time (RT). In Experiment 2, a task
      switch delayed the onset of the effect of lexical status on the ERP by about the
      same extent that it prolonged the RT. These effects indicate an early locus of
      (most of) the residual switch cost: We propose that this reflects a form of task
      related attentional inertia. Other findings have implications for the
      automaticity of lexical access: Effects of frequency, lexicality, and
      orthographic familiarity on ERPs in the symmetry task indicated involuntary, but
      attenuated, orthographic and lexical processing even when attention was focused
      on a nonlexical property.

PMID- 25844624
TI  - Individual differences in ensemble perception reveal multiple, independent levels
      of ensemble representation.
AB  - Ensemble perception, including the ability to "see the average" from a group of
      items, operates in numerous feature domains (size, orientation, speed, facial
      expression, etc.). Although the ubiquity of ensemble representations is well
      established, the large-scale cognitive architecture of this process remains
      poorly defined. We address this using an individual differences approach. In a
      series of experiments, observers saw groups of objects and reported either a
      single item from the group or the average of the entire group. High-level
      ensemble representations (e.g., average facial expression) showed complete
      independence from low-level ensemble representations (e.g., average orientation).
      In contrast, low-level ensemble representations (e.g., orientation and color)
      were correlated with each other, but not with high-level ensemble representations
      (e.g., facial expression and person identity). These results suggest that there
      is not a single domain-general ensemble mechanism, and that the relationship
      among various ensemble representations depends on how proximal they are in
      representational space.

PMID- 25844625
TI  - Text exposure predicts spoken production of complex sentences in 8- and 12-year
      old children and adults.
AB  - There is still much debate about the nature of the experiential and maturational
      changes that take place during childhood to bring about the sophisticated
      language abilities of an adult. The present study investigated text exposure as a
      possible source of linguistic experience that plays a role in the development of
      adult-like language abilities. Corpus analyses of object and passive relative
      clauses (Object: The book that the woman carried; Passive: The book that was
      carried by the woman) established the frequencies of these sentence types in
      child-directed speech and children's literature. We found that relative clauses
      of either type were more frequent in the written corpus, and that the ratio of
      passive to object relatives was much higher in the written corpus as well. This
      analysis suggests that passive relative clauses are much more frequent in a
      child's linguistic environment if they have high rates of text exposure. We then
      elicited object and passive relative clauses using a picture-description
      production task with 8- and 12-year-old children and adults. Both group and
      individual differences were consistent with the corpus analyses, such that older
      individuals and individuals with more text exposure produced more passive
      relative clauses. These findings suggest that the qualitatively different
      patterns of text versus speech may be an important source of linguistic
      experience for the development of adult-like language behavior.

PMID- 25844626
TI  - Flash fire and slow burn: women's cardiovascular reactivity and recovery
      following hostile and benevolent sexism.
AB  - Women's cardiovascular responses to sexist treatment are documented, but
      researchers have yet to consider these responses separately as a function of
      sexism type (hostile vs. benevolent). This study demonstrates distinct effects of
      hostile and benevolent sexism for women's cardiovascular responses that indicate
      increased risk for cardiovascular disease. Female participants performed a
      demanding insight task after exposure to a male researcher who offered them a
      hostilely sexist, benevolently sexist, or nonsexist comment. Women displayed
      heightened cardiovascular reactivity (increases from baseline) during the task
      following hostile sexism, and they displayed impaired cardiovascular recovery
      (return to baseline after the task) following benevolent sexism. The effects seen
      in the hostile condition were mediated by self-reported anger. These findings
      indicate that women's affective responses to hostile and benevolent sexism differ
      but that exposure to both forms of sexism may have negative cardiovascular
      consequences.

PMID- 25844627
TI  - Dynamics of postdecisional processing of confidence.
AB  - Most cognitive theories assume that confidence and choice happen simultaneously
      and are based on the same information. The 3 studies presented in this article
      instead show that confidence judgments can arise, at least in part, from a
      postdecisional evidence accumulation process. As a result of this process,
      increasing the time between making a choice and confidence judgment improves
      confidence resolution. This finding contradicts the notion that confidence
      judgments are biased by decision makers seeking confirmatory evidence. Further
      analysis reveals that the improved resolution is due to a reduction in confidence
      in incorrect responses, while confidence in correct responses remains relatively
      constant. These results are modeled with a sequential sampling process that
      allows evidence accumulation to continue after a choice is made and maps the
      amount of accumulated evidence onto a confidence rating. The cognitive modeling
      analysis reveals that the rate of evidence accumulation following a choice does
      slow relative to the rate preceding choice. The analysis also shows that the
      asymmetry between confidence in correct and incorrect choices is compatible with
      state-dependent decay in the accumulated evidence: Evidence consistent with the
      current state results in a deceleration of accumulated evidence and consequently
      evidence appears to have a decreasing impact on observed confidence. In contrast,
      evidence inconsistent with the current state results in an acceleration of
      accumulated evidence toward the opposite direction and consequently evidence
      appears to have an increasing impact on confidence. Taken together, this process
      level understanding of confidence suggests a simple strategy for improving
      confidence accuracy: take a bit more time to make confidence judgments.

PMID- 25844628
TI  - Disfluent fonts don't help people solve math problems.
AB  - Prior research suggests that reducing font clarity can cause people to consider
      printed information more carefully. The most famous demonstration showed that
      participants were more likely to solve counterintuitive math problems when they
      were printed in hard-to-read font. However, after pooling data from that
      experiment with 16 attempts to replicate it, we find no effect on solution rates.
      We examine potential moderating variables, including cognitive ability,
      presentation format, and experimental setting, but we find no evidence of a
      disfluent font benefit under any conditions. More generally, though disfluent
      fonts slightly increase response times, we find little evidence that they
      activate analytic reasoning.

PMID- 25844629
TI  - Confidence intervals for distinguishing ordinal and disordinal interactions in
      multiple regression.
AB  - Distinguishing between ordinal and disordinal interaction in multiple regression
      is useful in testing many interesting theoretical hypotheses. Because the
      distinction is made based on the location of a crossover point of 2 simple
      regression lines, confidence intervals of the crossover point can be used to
      distinguish ordinal and disordinal interactions. This study examined 2 factors
      that need to be considered in constructing confidence intervals of the crossover
      point: (a) the assumption about the sampling distribution of the crossover point,
      and (b) the possibility of abnormally wide confidence intervals for the crossover
      point. A Monte Carlo simulation study was conducted to compare 6 different
      methods for constructing confidence intervals of the crossover point in terms of
      the coverage rate, the proportion of true values that fall to the left or right
      of the confidence intervals, and the average width of the confidence intervals.
      The methods include the reparameterization, delta, Fieller, basic bootstrap,
      percentile bootstrap, and bias-corrected accelerated bootstrap methods. The
      results of our Monte Carlo simulation study suggest that statistical inference
      using confidence intervals to distinguish ordinal and disordinal interaction
      requires sample sizes more than 500 to be able to provide sufficiently narrow
      confidence intervals to identify the location of the crossover point.

PMID- 25844630
TI  - Advancing theory and practice through collaborative research in environmental
      gerontology.

PMID- 25844631
TI  - Effects of caffeine and its metabolite paraxanthine on intracranial self
      stimulation in male rats.
AB  - Caffeine is the most widely used psychostimulant in the world, though preclinical
      studies suggest weaker evidence for abuse-related effects than stimulants with
      high abuse liability, such as amphetamine or cocaine. Intracranial self
      stimulation (ICSS) is 1 procedure used to assess the abuse liability of drugs,
      and previous studies have produced mixed results regarding whether caffeine
      produces an abuse-related facilitation of ICSS. This study assessed both caffeine
      and its main metabolite in humans, paraxanthine, using a frequency-rate ICSS
      procedure and compared their effects to those of amphetamine and cocaine. Male
      Sprague-Dawley rats were implanted with intracranial electrodes targeting the
      medial forebrain bundle and trained to respond under a fixed-ratio 1 schedule for
      brain stimulation that varied across a range of frequencies (56-158 Hz in 0.05
      log increments). Data analysis focused on 3 dependent measures: reinforced
      responding (defined as responses that produced brain stimulation), nonreinforced
      responding (defined as responses that occurred during each 0.5 s brain
      stimulation and that did not produce additional stimulation), and total
      responding (reinforced plus nonreinforced responding). Both amphetamine and
      cocaine produced robust increases in total, reinforced, and nonreinforced
      responses. Caffeine also increased total, reinforced, and nonreinforced
      responses, but the caffeine dose-effect curve had an inverted-U shape, and peak
      ICSS facilitation was less than that produced by amphetamine or cocaine.
      Paraxanthine increased only total responses and nonreinforced responses. These
      results suggest that paraxanthine has low abuse liability and does not mediate
      abuse-related effects of caffeine.

PMID- 25844633
TI  - Mapping the BH3 Binding Interface of Bcl-xL, Bcl-2, and Mcl-1 Using Split
      Luciferase Reassembly.
AB  - The recognition of helical BH3 domains by Bcl-2 homology (BH) receptors plays a
      central role in apoptosis. The residues that determine specificity or promiscuity
      in this interactome are difficult to predict from structural and computational
      data. Using a cell free split-luciferase system, we have generated a 276 pairwise
      interaction map for 12 alanine mutations at the binding interface for three
      receptors, Bcl-xL, Bcl-2, and Mcl-1, and interrogated them against BH3 helices
      derived from Bad, Bak, Bid, Bik, Bim, Bmf, Hrk, and Puma. This panel, in
      conjunction with previous structural and functional studies, starts to provide a
      more comprehensive portrait of this interactome, explains promiscuity, and
      uncovers surprising details; for example, the Bcl-xL R139A mutation disrupts
      binding to all helices but the Bad-BH3 peptide, and Mcl-1 binding is particularly
      perturbed by only four mutations of the 12 tested (V220A, N260A, R263A, and
      F319A), while Bcl-xL and Bcl-2 have a more diverse set of important residues
      depending on the bound helix. 

PMID- 25844634
TI  - Ultraclean patterned transfer of single-layer graphene by recyclable pressure
      sensitive adhesive films.
AB  - We report an ultraclean, cost-effective, and easily scalable method of
      transferring and patterning large-area graphene using pressure sensitive adhesive
      films (PSAFs) at room temperature. This simple transfer is enabled by the
      difference in wettability and adhesion energy of graphene with respect to PSAF
      and a target substrate. The PSAF-transferred graphene is found to be free from
      residues and shows excellent charge carrier mobility as high as ~17,700 cm(2)/V.s
      with less doping compared to the graphene transferred by thermal release tape
      (TRT) or poly(methyl methacrylate) (PMMA) as well as good uniformity over large
      areas. In addition, the sheet resistance of graphene transferred by recycled PSAF
      does not change considerably up to 4 times, which would be advantageous for more
      cost-effective and environmentally friendly production of large-area graphene
      films for practical applications.

PMID- 25844632
TI  - Modeling naturalistic craving, withdrawal, and affect during early nicotine
      abstinence: A pilot ecological momentary assessment study.
AB  - Despite the critical role of withdrawal, craving, and positive affect (PA) and
      negative affect (NA) in smoking relapse, relatively little is known about the
      temporal and predictive relationship between these constructs within the first
      day of abstinence. This pilot study aims to characterize dynamic changes in
      withdrawal, craving, and affect over the course of early abstinence using
      ecological momentary assessment. Beginning immediately after smoking, moderate
      and heavy smoking participants (n = 15 per group) responded to hourly surveys
      assessing craving, withdrawal, NA, and PA. Univariate and multivariate multilevel
      random coefficient modeling was used to describe the progression of craving,
      withdrawal/NA, and PA and to test correlations between these constructs at the
      subject level over the course of early abstinence. Heavy smokers reported greater
      craving from 1-4 hr of abstinence and greater withdrawal/NA after 3 or more hours
      as compared with moderate smokers. Level of withdrawal/NA was strongly positively
      associated with craving, and PA was negatively correlated with craving; however,
      the temporal dynamics of these correlations differed substantially. The
      association between withdrawal/NA and craving decreased over early abstinence,
      whereas the reverse was observed for PA. These findings can inform experimental
      studies of nicotine abstinence as well as their clinical applications to smoking
      cessation efforts. In particular, these results help to elucidate the role of PA
      in nicotine abstinence by demonstrating its independent association with nicotine
      craving over and above withdrawal/NA. If supported by future studies, these
      findings can refine experimental methods and clinical approaches for smoking
      cessation.

PMID- 25844635
TI  - o-Boronato- and o-Trifluoroborato-Phosphonium Salts Supported by L-alpha-Amino
      Acid Side Chain.
AB  - The synthesis of o-boronato- and o-trifluoroborato-phosphonium salts supported by
      the L-amino acid side chain is described. The synthesis of these new class of
      amino acid derivatives was achieved by stereoselective quaternization of o
      (pinacolato)boronatophenylphosphine with beta- or gamma-iodo amino acid
      derivatives which are prepared from L-serine or L-aspartic acid, respectively.
      The quaternization of the phosphine was performed using either iodo amino ester
      or carboxylic acid derivatives. In addition, free carboxylic acid and amine
      derivatives were obtained by saponification or HCl acidolysis of o-boronato
      phosphonium amino esters, respectively. The usefulness of these compounds in
      peptide coupling was demonstrated by coupling an o-boronato-phosphonium amino
      ester with an aspartic acid moiety. When the o-boronato-phosphonium amino acid or
      dipeptide derivatives were mixed with fluoride, the corresponding o
      trifluoroborated products were cleanly and rapidly obtained in high isolated
      yields. The hydrolysis of these compounds at room temperature using a phosphate
      buffer pH 7/CD3CN mixture has shown only traces of free fluoride F(-) after
      several days. Finally, a preliminary radiolabeling essay has proven the facile
      [(18)F]-fluoride incorporation and high stability of the radiolabeled product in
      aqueous conditions. Indeed, this new class of boron-phosphonium amino acid
      derivatives shows promising properties for their applications in synthesis and
      labeling of peptides.

PMID- 25844636
TI  - Bexarotene reduces blood-brain barrier permeability in cerebral ischemia
      reperfusion injured rats.
AB  - BACKGROUND: Matrix metalloproteinase-9 (MMP-9) over-expression disrupts the blood
      brain barrier (BBB) in the ischemic brain. The retinoid X receptor agonist
      bexarotene suppresses MMP-9 expression in endothelial cells and displays
      neuroprotective effects. Therefore, we hypothesized that bexarotene may have a
      beneficial effect on I/R-induced BBB dysfunction. METHODS: A total of 180 rats
      were randomized into three groups (n = 60 each): (i) a sham-operation group, (ii)
      a cerebral ischemia-reperfusion (I/R) group, and (iii) an I/R+bexarotene group.
      Brain water content was measured by the dry wet weight method. BBB permeability
      was analyzed by Evans Blue staining and the magnetic resonance imaging contrast
      agent Omniscan. MMP-9 mRNA expression, protein expression, and activity were
      assessed by reverse transcription polymerase chain reaction, Western blotting,
      and gelatin zymography, respectively. Apolipoprotein E (apoE), claudin-5, and
      occludin expression were analyzed by Western blotting. RESULTS: After 24 h, 48 h,
      and 72 h post-I/R, several effects were observed with bexarotene administration:
      (i) brain water content and BBB permeability were significantly reduced; (ii) MMP
      9 mRNA and protein expression as well as activity were significantly decreased;
      (iii) claudin-5 and occludin expression were significantly increased; and (iv)
      apoE expression was significantly increased. CONCLUSIONS: Bexarotene decreases
      BBB permeability in rats with cerebral I/R injury. This effect may be due in part
      to bexarotene's upregulation of apoE expression, which has been previously shown
      to reduce BBB permeability through suppressing MMP-9-mediated degradation of the
      tight junction proteins claudin-5 and occludin. This work offers insight to aid
      future development of therapeutic agents for cerebral I/R injury in human
      patients.

PMID- 25844637
TI  - Intrinsic photocatalytic assessment of reactively sputtered TiO2 films.
AB  - Thin TiO2 films were prepared by DC magnetron reactive sputtering at different
      oxygen partial pressures. Depending on the oxygen partial pressure during
      sputtering, a transition from metallic Ti to TiO2 was identified by spectroscopic
      ellipsometry. The crystalline nature of the film developed during a subsequent
      annealing step, resulting in thin anatase TiO2 layers, displaying photocatalytic
      activity. The intrinsic photocatalytic activity of the catalysts was evaluated
      for the degradation of methylene blue (MB) using a microfluidic reactor. A
      numerical model was employed to extract the intrinsic reaction rate constants.
      High conversion rates (90% degradation within 20 s residence time) were observed
      within these microreactors because of the efficient mass transport and light
      distribution. To evaluate the intrinsic reaction kinetics, we argue that mass
      transport has to be accounted for. The obtained surface reaction rate constants
      demonstrate very high reactivity for the sputtered TiO2 films. Only for the
      thinnest film, 9 nm, slightly lower kinetics were observed. 

PMID- 25844638
TI  - Improving executive functioning in children with ADHD: training multiple
      executive functions within the context of a computer game. a randomized double
      blind placebo controlled trial.
AB  - INTRODUCTION: Executive functions (EFs) training interventions aimed at ADHD
      symptom reduction have yielded mixed results. Generally, these interventions
      focus on training a single cognitive domain (e.g., working memory [WM],
      inhibition, or cognitive-flexibility). However, evidence suggests that most
      children with ADHD show deficits on multiple EFs, and that these EFs are largely
      related to different brain regions. Therefore, training multiple EFs might be a
      potentially more effective strategy to reduce EF-related ADHD symptoms. METHODS:
      Eighty-nine children with a clinical diagnosis of ADHD (aged 8-12) were
      randomized to either a full-active-condition where visuospatial WM, inhibition
      and cognitive-flexibility were trained, a partially-active-condition where
      inhibition and cognitive-flexibility were trained and the WM-training task was
      presented in placebo-mode, or to a full placebo-condition. Short-term and long
      term (3-months) effects of this gamified, 25-session, home-based computer
      training were evaluated on multiple outcome domains. RESULTS: During training
      compliance was high (only 3% failed to meet compliance criteria). After training,
      only children in the full-active condition showed improvement on measures of
      visuospatial short-term-memory (STM) and WM. Inhibitory performance and
      interference control only improved in the full-active- and the partially-active
      condition. No Treatment-condition x Time interactions were found for cognitive
      flexibility, verbal WM, complex-reasoning, nor for any parent-, teacher-, or
      child-rated ADHD behaviors, EF-behaviors, motivational behaviors, or general
      problem behaviors. Nonetheless, almost all measures showed main Time-effects,
      including the teacher-ratings. CONCLUSIONS: Improvements on inhibition and
      visuospatial STM and WM were specifically related to the type of treatment
      received. However, transfer to untrained EFs and behaviors was mostly nonspecific
      (i.e., only interference control improved exclusively in the two EF training
      conditions). As such, in this multiple EF-training, mainly nonspecific treatment
      factors - as opposed to the specific effects of training EFs-seem related to far
      transfer effects found on EF and behavior. TRIAL REGISTRATION: trialregister.nl
      NTR2728. Registry name: improving executive functioning in children with ADHD:
      training executive functions within the context of a computer game; registry
      number: NTR2728.

PMID- 25844639
TI  - UV-Induced DNA Interstrand Cross-Linking and Direct Strand Breaks from a New Type
      of Binitroimidazole Analogue.
AB  - Four novel photoactivated binitroimidazole prodrugs were synthesized. These
      agents produced DNA interstrand cross-links (ICLs) and direct strand breaks (DSB)
      upon UV irradiation, whereas no or very few DNA ICLs and DSBs were observed
      without UV treatment. Although these four molecules (1-4) contain the same
      binitroimidazole moiety, they bear four different leaving groups, which resulted
      in their producing different yields of DNA damage. Compound 4, with nitrogen
      mustard as a leaving group, showed the highest ICL yield. Surprisingly, compounds
      1-3, without any alkylating functional group, also induced DNA ICL formation,
      although they did so with lower yields, which suggested that the binitroimidazole
      moiety released from UV irradiation of 1-3 is capable of cross-linking DNA. The
      DNA cross-linked products induced by these compounds were completely destroyed
      upon 1.0 M piperidine treatment at 90  degrees C (leading to cleavage at dG
      sites), which revealed that DNA cross-linking mainly occurred via alkylation of
      dGs. We proposed a possible mechanism by which alkylating agents were released
      from these compounds. HRMS and NMR analysis confirmed that free nitrogen mustards
      were generated by UV irradiation of 4. Suppression of DNA ICL and DSB formation
      by a radical trap, TEMPO, indicated the involvement of free radicals in the photo
      reactions of 3 and 4 with DNA. On the basis of these data, we propose that UV
      irradiation of compounds 1-4 generated a binitroimidazole intermediate that cross
      links DNA. The higher ICL yield observed with 4 resulted from the amine effector
      nitrogen mustard released from UV irradiation. 

PMID- 25844640
TI  - Gas-solid reaction kinetics of ZnFe2O4 formation from 907 to 1100  degrees C.
AB  - The reaction kinetics of Zn vapor with Fe3O4 (magnetite) were studied from 907 to
      1100  degrees C using a new experimental setup that only allows contact between
      the reactants through a gas-solid reaction. Hematite was used to create the
      reaction pellets. Because of the reducing atmosphere in the setup, a magnetite
      layer is formed on the outside of the pellet, which in turn reacts with the Zn
      vapor. After reaction, Zn concentration profiles were measured in the reacted
      magnetite layer using field-emission gun electron probe microanalysis. The
      reaction was confirmed to be diffusion-controlled. The effect of both volume and
      grain-boundary diffusion was observed in each experiment. The temperature
      dependence of both the volume and grain-boundary diffusion coefficients was
      obtained along with the activation energies of the diffusion coefficients. This
      study provides crucial information for the development of technologies that are
      dependent on the reaction. One example is the in-process separation technology
      for the separation of Zn vapor from electric arc furnace off-gas. 

PMID- 25844641
TI  - Measuring melittin uptake into hydrogel nanoparticles with near-infrared single
      nanoparticle surface plasmon resonance microscopy.
AB  - This paper describes how changes in the refractive index of single hydrogel
      nanoparticles (HNPs) detected with near-infrared surface plasmon resonance
      microscopy (SPRM) can be used to monitor the uptake of therapeutic compounds for
      potential drug delivery applications. As a first example, SPRM is used to measure
      the specific uptake of the bioactive peptide melittin into N-isopropylacrylamide
      (NIPAm)-based HNPs. Point diffraction patterns in sequential real-time SPRM
      differential reflectivity images are counted to create digital adsorption binding
      curves of single 220 nm HNPs from picomolar nanoparticle solutions onto
      hydrophobic alkanethiol-modified gold surfaces. For each digital adsorption
      binding curve, the average single nanoparticle SPRM reflectivity response,
      ?Delta%RNP?, was measured. The value of ?Delta%RNP? increased linearly from 1.04
      +/- 0.04 to 2.10 +/- 0.10% when the melittin concentration in the HNP solution
      varied from zero to 2.5 MUM. No change in the average HNP size in the presence of
      melittin is observed with dynamic light scattering measurements, and no increase
      in ?Delta%RNP? is observed in the presence of either FLAG octapeptide or bovine
      serum albumin. Additional bulk fluorescence measurements of melittin uptake into
      HNPs are used to estimate that a 1% increase in ?Delta%RNP? observed in SPRM
      corresponds to the incorporation of approximately 65000 molecules into each 220
      nm HNP, corresponding to roughly 4% of its volume. The lowest detected amount of
      melittin loading into the 220 nm HNPs was an increase in ?Delta%RNP? of 0.15%,
      corresponding to the absorption of 10000 molecules. 

PMID- 25844642
TI  - Relative age effects in athletic sprinting and corrective adjustments as a
      solution for their removal.
AB  - Relative Age Effects (RAEs) refer to the selection and performance differentials
      between children and youth who are categorized in annual-age groups. In the
      context of Swiss 60m athletic sprinting, 7761 male athletes aged 8 - 15 years
      were analysed, with this study examining whether: (i) RAE prevalence changed
      across annual age groups and according to performance level (i.e., all athletes,
      Top 50%, 25% & 10%); (ii) whether the relationship between relative age and
      performance could be quantified, and corrective adjustments applied to test if
      RAEs could be removed. Part one identified that when all athletes were included,
      typical RAEs were evident, with smaller comparative effect sizes, and
      progressively reduced with older age groups. However, RAE effect sizes increased
      linearly according to performance level (i.e., all athletes - Top 10%) regardless
      of age group. In part two, all athletes born in each quartile, and within each
      annual age group, were entered into linear regression analyses. Results
      identified that an almost one year relative age difference resulted in mean
      expected performance differences of 10.1% at age 8, 8.4% at 9, 6.8% at 10, 6.4%
      at 11, 6.0% at 12, 6.3% at 13, 6.7% at 14, and 5.3% at 15. Correction adjustments
      were then calculated according to day, month, quarter, and year, and used to
      demonstrate that RAEs can be effectively removed from all performance levels, and
      from Swiss junior sprinting more broadly. Such procedures could hold significant
      implications for sport participation as well as for performance assessment,
      evaluation, and selection during athlete development. 

PMID- 25844643
TI  - Lipid Selectivity, Orientation, and Extent of Membrane Binding of Nonacylated
      RP2.
AB  - Retinitis pigmentosa 2 (RP2) is an ubiquitary protein of 350 residues. The N
      terminus of RP2 contains putative sites of myristoylation and palmitoylation. The
      dually acylated protein is predominantly localized to the plasma membrane.
      However, clinically occurring substitution mutations of RP2 in photoreceptors
      lead to the expression of a nonacylated protein, which was shown to be misrouted
      to intracellular organelles using different cell lines. However, the parameters
      responsible for the modulation of the membrane binding of nonacylated RP2 (naRP2)
      are still largely unknown. The maximal insertion pressure of naRP2 has thus been
      determined after its injection into the subphase underneath monolayers of
      phospholipids, which are typical of photoreceptor membranes. These data
      demonstrated that naRP2 shows a preferential binding to saturated phospholipid
      monolayers. Moreover, polarization modulation infrared reflection absorption
      spectroscopy has allowed comparison of the secondary structure of this protein in
      solution and upon binding to phospholipid monolayers. In addition, simulations of
      these spectra have allowed to determine that the beta-helix of naRP2 has an
      orientation of 60 degrees  with respect to the normal, which remains unchanged
      regardless of the type of phospholipid. Finally, ellipsometric measurements of
      naRP2 demonstrated that its particular affinity for saturated phospholipids can
      be explained by its larger extent of insertion in this phospholipid monolayer
      compared to that in polyunsaturated phospholipid monolayers. 

PMID- 25844645
TI  - Octanol-Water Partition Coefficient from 3D-RISM-KH Molecular Theory of Solvation
      with Partial Molar Volume Correction.
AB  - The octanol-water partition coefficient is an important physical-chemical
      characteristic widely used to describe hydrophobic/hydrophilic properties of
      chemical compounds. The partition coefficient is related to the transfer free
      energy of a compound from water to octanol. Here, we introduce a new protocol for
      prediction of the partition coefficient based on the statistical-mechanical, 3D
      RISM-KH molecular theory of solvation. It was shown recently that with the
      compound-solvent correlation functions obtained from the 3D-RISM-KH molecular
      theory of solvation, the free energy functional supplemented with the correction
      linearly related to the partial molar volume obtained from the Kirkwood-Buff/3D
      RISM theory, also called the "universal correction" (UC), provides accurate
      prediction of the hydration free energy of small compounds, compared to explicit
      solvent molecular dynamics [ Palmer , D. S. ; J. Phys.: Condens. Matter 2010 , 22
      , 492101 ]. Here we report that with the UC reparametrized accordingly this
      theory also provides an excellent agreement with the experimental data for the
      solvation free energy in nonpolar solvent (1-octanol) and so accurately predicts
      the octanol-water partition coefficient. The performance of the Kovalenko-Hirata
      (KH) and Gaussian fluctuation (GF) functionals of the solvation free energy, with
      and without UC, is tested on a large library of small compounds with diverse
      functional groups. The best agreement with the experimental data for octanol
      water partition coefficients is obtained with the KH-UC solvation free energy
      functional. 

PMID- 25844644
TI  - Restoring susceptibility induced MRI signal loss in rat brain at 9.4 T: A step
      towards whole brain functional connectivity imaging.
AB  - The aural cavity magnetic susceptibility artifact leads to significant echo
      planar imaging (EPI) signal dropout in rat deep brain that limits acquisition of
      functional connectivity fcMRI data. In this study, we provide a method that
      recovers much of the EPI signal in deep brain. Needle puncture introduction of a
      liquid-phase fluorocarbon into the middle ear allows acquisition of rat fcMRI
      data without signal dropout. We demonstrate that with seeds chosen from
      previously unavailable areas, including the amygdala and the insular cortex, we
      are able to acquire large scale networks, including the limbic system. This tool
      allows EPI-based neuroscience and pharmaceutical research in rat brain using
      fcMRI that was previously not feasible. 

PMID- 25844647
TI  - High-efficiency thermoelectrics with functionalized graphene.
AB  - Graphene superlattices made with chemical functionalization offer the possibility
      of tuning both the thermal and electronic properties via nanopatterning of the
      graphene surface. Using classical and quantum mechanical calculations, we predict
      that suitable chemical functionalization of graphene can introduce peaks in the
      density of states at the band edge that result in a large enhancement in the
      Seebeck coefficient, leading to an increase in the room-temperature power factor
      of a factor of 2 compared to pristine graphene, despite the degraded electrical
      conductivity. Furthermore, the presence of patterns on graphene reduces the
      thermal conductivity, which when taken together leads to an increase in the
      figure of merit for functionalized graphene by up to 2 orders of magnitude over
      that of pristine graphene, reaching its maximum ZT ~ 3 at room temperature
      according to our calculations. These results suggest that appropriate chemical
      functionalization could lead to efficient graphene-based thermoelectric
      materials. 

PMID- 25844646
TI  - Inhibitors of eicosanoid biosynthesis influencing the transcripts level of
      sHSP21.4 gene induced by pathogen infections, in Antheraea pernyi.
AB  - Small heat shock proteins (sHSPs) can regulate protein folding and protect cells
      from stress. To investigate the role of sHSPs in the silk-producing insect
      Antheraea pernyi response to microorganisms, a sHsp gene termed as Ap-sHSP21.4,
      was identified. This gene encoded a 21.4 kDa protein which shares the conserved
      structure of insect sHsps and belongs to sHSP21.4 family. Ap-sHSP21.4 was highly
      expressed in fat body and up-regulated in midgut and fat body of A. pernyi
      challenged with Escherichia coli, Beauveria bassiana and nuclear polyhedrosis
      virus (NPV), which was determined by quantitative real-time PCR. Meanwhile, knock
      down of Ap-sHSP21.4 with dsRNA result in the decrease at the expression levels of
      several immune response-related genes (defensin, Dopa decarboxylase, Toll1,
      lysozyme and Kazal-type serine protease inhibitor). Additionally, the impact of
      eicosanoid biosynthesis on the expression of Ap-sHSP21.4 response to NPV was
      determined using qPCR, inhibitors of eicosanoid biosynthesis significantly
      suppress Ap-HSP21.4 expression upon NPV challenge. All together, Ap-sHSP21.4 was
      involved in the immunity of A. pernyi against microorganism and possibly mediated
      by eicosanoids pathway. These results will shed light in the understanding of the
      pathogen-host interaction in A. pernyi. 

PMID- 25844648
TI  - Removal of natural estrogens and their conjugates in municipal wastewater
      treatment plants: a critical review.
AB  - This article reviews studies focusing on the removal performance of natural
      estrogens in municipal wastewater treatment plants (WWTPs). Key factors
      influencing removal include: sludge retention time (SRT), aeration, temperature,
      mixed liquor suspended solids (MLSS), and substrate concentration. Batch studies
      show that natural estrogens should biodegrade well; however, batch observations
      do not always agree with observations from full-scale municipal WWTPs. To explain
      this discrepancy, deconjugation kinetics of estrogen conjugates in lab-scale
      studies were examined and compared. Most estrogen conjugates with slow
      deconjugation rates are unlikely to be easily removed; others could be cleaved in
      WWTP settings. Nevertheless, some estrogens cleaved from their conjugates may be
      found in treated effluent, because deconjugation requires several hours or
      longer, and there is insufficient rest time for the biodegradation of the cleaved
      natural estrogens in the WWTP. Therefore, WWTP removals of natural estrogens are
      likely to be underestimated when estrogen conjugates are present in raw
      wastewater. This review suggests that biodeconjugation of estrogen conjugates
      should be enhanced to more effectively remove natural estrogens in WWTPs. 

PMID- 25844649
TI  - National accounts of subjective well-being.
AB  - Diener (2000) proposed that National Accounts of Well-Being be created to
      complement existing economic and social indicators that reflect the quality of
      life in nations. These national accounts can provide valuable information to
      policymakers and other leaders. Systematic measurement of subjective well-being
      provides novel information about the quality of life in societies, and it allows
      for the accumulation of detailed information regarding the circumstances that are
      associated with high subjective well-being. Thus, accounts of subjective well
      being can help decision makers evaluate policies that improve societies beyond
      economic development. Progress with well-being accounts has been notable:
      Prestigious scientific and international institutions have recommended the
      creation of such national accounts, and these recommendations have been adopted
      in some form in over 40 nations. In addition, increasing research into policy
      relevant questions reveals the importance of the accounts for policy.
      Psychologists can enlarge their role in the formulation and adoption of policies
      by actively studying and using accounts of subjective well-being to evaluate and
      support the policies they believe are needed.

PMID- 25844650
TI  - Strengthening psychology's workforce for older adults: Implications of the
      Institute of Medicine's report to Congress.
AB  - Professional psychology faces an urgent crisis, which the following facts paint
      in stark relief. Adults over age 65 will rise to 20% of the U.S. population over
      the next 15 years and already account for a third of the country's health care
      expenditures. Up to 8 million older adults experience mental health and substance
      use conditions in a given year, yet most psychologists receive no training in
      their assessment and treatment. No more than an estimated 4%, or 3,000,
      psychologists nationwide specialize in geropsychology; a ratio approaching 3,000
      to 1. A small group of advocates within the profession have sounded the alarm and
      worked to strengthen geropsychology as a specialty, but this has had very limited
      impact on the actual supply of psychologists qualified to provide services to
      this population. In 2012, an Institute of Medicine (IOM) committee released a
      report on the crisis regarding the mental health and substance use workforce for
      older adults. Drawing on that report, a team composed of geropsychologists, along
      with psychologists who served on the IOM committee, identifies in this article
      priority areas for workforce development. The authors assess the progress of
      psychology in each of these areas and offer a set of recommendations for future
      efforts by this profession to develop its own workforce and to strengthen the
      ability of other caregivers to address the behavioral health needs of older
      adults. Strengthening its own workforce and responding to the needs of this
      population is imperative if psychology is to maintain its relevance as a health
      profession and meet its ethical obligations to an increasingly diverse society.

PMID- 25844651
TI  - Phyllis Bronstein (1939-2012).
AB  - This article memorializes Phyllis Bronstein (1939-2012). Bronstein was a feminist
      scholar, social and clinical psychologist, and activist for social justice. At
      the University of Vermont, she engaged almost 100 undergraduates in her research
      teams, mentored the research and professional development of 43 graduate
      students, and trained over 90 clinical psychology students in the feminist family
      therapy program she developed. Bronstein published over 45 chapters and journal
      articles, and three edited books. One stream of her scholarship focused on
      sociocultural factors in parenting, child and adolescent development, with
      studies conducted in the United States and Mexico. Bronstein is perhaps best
      known for two volumes on the integration of multicultural and gender issues into
      the psychology curriculum, coedited with Kathryn Quina and published by the
      American Psychological Association. Bronstein's third stream of scholarship
      addressed sexist, racist, and ageist practices in academic and clinical
      professions.

PMID- 25844652
TI  - Sandra Lipsitz Bem (1944-2014).
AB  - This article memorializes Sandra Lipsitz Bem (1944-2014). Bem was a feminism
      psychologist whose incisive writing and research transformed the psychology of
      gender and contributed significantly to our understanding of sex-typing,
      psychological androgyny, gender schema theory, and sexual inequality. Bem and her
      husband, Daryl Bem, were active in the feminist community in Pittsburgh, and
      worked with the National Organization for Women to challenge gender-segregated
      job advertisements in a lawsuit against the Pittsburgh Press in 1969. The Bems co
      wrote an influential article, "Case Study of a Nonconscious Ideology: Training
      the Woman to Know Her Place" (1970) using the word "sexism" when it was not
      widely known. She created the Bem Sex-Role Inventory (BSRI) and conducted
      research showing that conventional gender typing was not necessarily correlated
      with psychological adjustment. Her publications won her enduring recognition and
      awards, including the American Psychological Association Distinguished Scientific
      Award for Early Career Contribution (1976), Distinguished Publication Awards from
      the Association for Women in Psychology (AWP; 1977, 1994), the Young Scholar
      Award from the American Association of University Women (1980), and,
      posthumously, the Distinguished Career Award (AWP, 2014).

PMID- 25844653
TI  - Selma Sapir (1916-2014).
AB  - This article memorializes Selma Sapir (1916-2014), a child psychologist and
      innovator in treating children with learning disabilities. Sapir authored or
      coauthored five books on treating and educating children with learning
      disabilities. She developed four tests: the Sapir Dimension of Learning, the
      Sapir Learning Lab Language Scale, the Sapir Self-Concept Scale, and the Sapir
      Developmental Scale. In 1997-1998, she served as president of the International
      Council of Psychologists (ICP). For many years, she was the ICP representative to
      the United Nations.

PMID- 25844654
TI  - Robert E. Thayer (1935-2014).
AB  - This article memorializes Robert E. Thayer (1935-2014). He was an internationally
      recognized leader in research into human mood, with influence inside and outside
      of the academy. In articles and books he advanced our understanding of the bases
      of human moods and the role mood plays in everyday life. His seminal work
      examined the biopsychology of mood, including a range of factors such as energy,
      tension, and arousal. He also developed a mood-related measure, the Activation
      Deactivation Adjective Check List (1964).

PMID- 25844655
TI  - Comment on the January 2015 cover of the American Psychologist.
AB  - This article comments on the January 2015 cover of the American Psychologist
      (Vol. 70, Issue 1). The caption linked to a picture of a wintry mountain scene
      said "Squaw Valley Meadow." Although a seemingly innocuous word to most people, a
      majority of Society of Indian Psychologists (SIP) members wanted to share what
      the term squaw , hereinafter deemed "s-word," invokes for many Native individuals
      as well as in the collective cultural memories of American Indian peoples. As a
      voice representative of Native peoples, the members of SIP are acutely aware of
      the many issues that need to be redressed, both within our own communities and in
      our relations with non-Native society. In the case of the cover art caption and
      the ire provoked by the use of the s-word, the members of SIP opted to take an
      opportunity to educate versus confront, and to inform versus chastise or accuse
      amid this polarized political climate of interracial tensions.

PMID- 25844656
TI  - Chronic pain and the adaptive significance of positive emotions.
AB  - The February-March 2014 special issue of the American Psychologist featured
      articles summarizing select contributions from the field of psychology to the
      assessment and treatment of chronic pain. The articles examined a range of
      psychosocial and family factors that influence individual adjustment and
      contribute to disparities in pain care. The reviews also considered the
      psychological correlates and neurophysiological mechanisms of specific pain
      treatments, including cognitive-behavioral therapy, hypnosis, acceptance and
      commitment therapy, mindfulness, and meditation. Although a number of articles
      emphasized the role that negative states of mind play in pain outcomes, positive
      emotions were given only brief mention. Here, we provide a rationale for the
      inclusion of positive emotions in chronic pain research.

PMID- 25844657
TI  - Tarasoff's catch-22.
AB  - Comments on the article by D. N. Bersoff (see record 2014-28692-002). Bersoff
      poses a much-needed challenge to the rationale of laws based on Tarasoff v.
      Regents of the University of California (1976), which exist in most states and
      require therapists to warn the intended victim, police, and/or others when a
      patient voices serious threats of violence. If Tarasoff-related laws were ever to
      be modified, research support would be required. To begin with, what is the
      experience of other countries that happen to address this issue differently and
      of the seven states that, according to Bersoff, have not adopted Tarasoff-related
      requirements? Another question is whether patients who are unwilling to invite
      the consequences of therapist disclosure ever reveal reportable intentions to
      their therapists anyway-say, by mistake or impulse-thus making current law
      marginally useful? Rules that undercut sacrosanct confidentiality create a catch
      22 in which the indisputable ethical necessity of informed consent has an
      unintended consequence- namely, therapy is preceded by informed consent but
      precluded by it.

PMID- 25844658
TI  - Plasmonic fano nanoantennas for on-chip separation of wavelength-encoded optical
      signals.
AB  - Here we suggest and realize an ultracompact plasmonic spectral-band demultiplexer
      for telecommunication wavelengths integrated onto an optical waveguide that
      couples two wavelength-encoded optical signals in the O- and the C-band in
      opposite directions of a silicon waveguide. In this way, we demonstrate a
      plasmonic key element for on-chip optical data processing that can also be used
      as a functional link between on- and off-chip optical signals. 

PMID- 25844659
TI  - Reactivity of CuI and CuBr toward dialkyl sulfides RSR: from discrete molecular
      Cu4I4S4 and Cu8I8S6 clusters to luminescent copper(I) coordination polymers.
AB  - The 1D coordination polymer (CP) [(Me2S)3{Cu2(MU-I)2}]n (1) is formed when CuI
      reacts with SMe2 in n-heptane, whereas in acetonitrile (MeCN), the reaction forms
      exclusively the 2D CP [(Me2S)3{Cu4(MU-I)4}]n (2) containing "flower-basket" Cu4I4
      units. The reaction product of CuI with MeSEt is also solvent-dependent, where
      the 1D polymer [(MeSEt)2{Cu4(MU3-I)2(MU2-I)2}(MeCN)2]n (3) containing "stepped
      cubane" Cu4I4 units is isolated in MeCN. In contrast, the reaction in n-heptane
      affords the 1D CP [(MeSEt)3{Cu4(MU3-I)4}]n (4) containing "closed-cubane" Cu4I4
      clusters. The reaction of MeSPr with CuI provides the structurally related 1D CP
      [(MeSPr)3{Cu4(MU3-I)4}]n (5), for which the X-ray structure has been determined
      at 115, 155, 195, 235, and 275 K, addressing the evolution of the metric
      parameters. Similarly to 4 and the previously reported CP [(Et2S)3{Cu4(MU3-I)4}]n
      (Inorg. Chem. 2010, 49, 5834), the 1D chain is built upon closed cubanes Cu4(MU3
      I)4 as secondary building units (SBUs) interconnected via MU-MeSPr ligands. The
      0D tetranuclear clusters [(L)4{Cu4(MU3-I)4}] [L = EtSPr (6), Pr2S (7)]
      respectively result from the reaction of CuI with EtSPr and n-Pr2S. With i-Pr2S,
      the octanuclear cluster [(i-Pr2S)6{Cu8(MU3-I)3}(MU4-I)2}] (8) is formed. An X-ray
      study has also been performed at five different temperatures for the 2D polymer
      [(Cu3Br3)(MeSEt)3]n (9) formed from the reaction between CuBr and MeSEt in
      heptane. The unprecedented framework of 9 consists of layers with alternating
      Cu(MU2-Br)2Cu rhomboids, which are connected through two MU-MeSEt ligands to
      tetranuclear open-cubane Cu4Br4 SBUs. MeSPr forms with CuBr in heptane the 1D CP
      [(Cu3Br3)(MeSPr)3]n (10), which is converted to a 2D metal-organic framework
      [(Cu5Br5)(MU2-MeSPr)3]n (11) incorporating pentanuclear [(Cu5(MU4-Br)(MU2-Br)]
      SBUs when recrystallized in MeCN. The thermal stability and photophysical
      properties of these materials are also reported. 

PMID- 25844660
TI  - Implementation and impact of an extended-hours service in mental health care:
      lessons learned.
AB  - OBJECTIVE: To describe the activity and impact of an extended-hours mental health
      service established to meet perceived need and improve service efficiency.
      Lessons developed in evaluation could usefully inform development of services in
      similar settings. SETTING: A specialist mental health service providing
      assessment and treatment to 330 000 catchment residents of an Australian capital
      city. METHODS: Pragmatic mixed-methods evaluation, combining review of 12 months
      service data and interviews with 65 stakeholders; with integration of descriptive
      statistics and thematic analysis of qualitative data. RESULTS: Over 12 months,
      2040 individuals were provided with a range of services during extended-hours,
      indicating that some sort of service was needed. However, evaluation demonstrated
      that flaws in assumptions underpinning the extended-hours service design,
      particularly regarding the population seeking after-hours care, necessitated
      adaptation of the proposed model. Ambiguity in purpose contributed to perceived
      lack of a cohesive identity, compounded by critical differences in the
      philosophies of care teams from which the extended-hours service clinicians were
      drawn. Nonetheless the service was considered effective by many stakeholders and
      co-location of different teams built collegiality within the service.
      CONCLUSIONS: A comprehensive needs analysis, enabling full description of target
      populations and their needs, should underpin establishment of any service. Such
      understanding is needed to ensure resources are appropriate. Importantly, because
      mental health clinicians are not interchangeable, matching philosophy of care and
      clinical skills to identified need is critical to quality and efficiency.

PMID- 25844661
TI  - Substrate activation strategies in rhodium(III)-catalyzed selective
      functionalization of arenes.
AB  - The possibility of developing new methods for the efficient construction of
      organic molecules via disconnections other than traditional functional group
      transformations has driven the interest in direct functionalization of C-H bonds.
      The ubiquity of C-H bonds makes such transformations attractive, but they also
      pose several challenges. The first is the reactivity and selectivity of C-H
      bonds. To achieve this, directing groups (DGs) are often installed that can
      enhance the effective concentration of the catalyst, leading to thermodynamically
      stable metallacyclic intermediates. However, the presence of a pendant directing
      group in the product is often undesirable and unnecessary. This may account for
      the limitation of applications of C-H functionalization reactions in more common
      and general uses. Thus, the development of removable or functionalizable
      directing groups is desirable. Another key problem is that the reactivity of the
      resulting M-C bond can be low, which may limit the scope of the coupling partners
      and hence limit the reaction patterns of C-H activation reactions. While the
      first Cp*Rh(III)-catalyzed C-H activation of arenes was reported only 7 years
      ago, significant progress has been made in this area in the past few years. We
      began our studies in this area in 2010, and we and others have demonstrated that
      diversified catalytic functionalization of arenes can be realized using
      Cp*Rh(III) complexes with high reactivity, stability, and functional group
      compatibility. This Account describes our efforts to solve some of these
      challenges using Rh(III) catalysis. We fulfilled our design and activation of the
      arene substrates by taking advantage of the nucleophilicity, electrophilicity,
      oxidizing potential, and properties of a participating ligand of the directing
      groups when the arenes are coupled with relatively reactive unsaturated partners
      such as alkenes and alkynes. These in situ funtionalizable roles of the DG
      allowed extensive chemical manipulation of the initial coupled product,
      especially in the construction of a diverse array of heterocycles. In the
      coupling of arenes with polar coupling partners, the polar Rh(III)-C(aryl) bond
      showed higher reactivity as both an organometallic reagent and a nucleophilic
      aryl source. The polar coupling partners were accordingly activated by virtue of
      umpolung, ring strain, and rearomatization. All of these transformations have
      been made possible by integration of the higher reactivity, stability, and
      compatibility of Rh(III)-C bonds into catalytic systems. We have demonstrated
      that to date some of these transformations can be achieved only under rhodium
      catalysis. In addition, by means of stoichiometric reactions, we have gained
      mechanistic insights into the interactions between the Rh-C bond and the other
      coupling partners, which have opened new avenues in future direct C-H
      functionalization reactions. 

PMID- 25844662
TI  - Estimation of polycyclic aromatic hydrocarbon variability in air using high
      volume, film, and vegetation as samplers.
AB  - Organic films and leaves provide a medium into which organic contaminants, such
      as polycyclic aromatic hydrocarbons (PAHs), can accumulate, resulting in a useful
      passive air sampler. In the present work, the temporal variability (weekly) in
      PAH concentrations and the fingerprint of films developed on window surfaces were
      investigated. Moreover, films and leaves of two tree species (Acer pseudoplatanus
      and Cornus mas) collected at the same time were used to derive PAH air
      concentrations and investigate their short-term variability. In general, the most
      abundant chemicals found in films were phenanthrene and pyrene (22%), followed by
      perylene (21%) and fluoranthene (16%), but the fingerprint (in contrast to leaves
      and air) changed over time. Leaf derived air concentrations were within a factor
      of 2 to 9 from measured values, while air concentrations back-calculated from
      films were within a factor of 2 to 53. This happened because predicted air
      concentrations using films and vegetation samplers (especially for low KOA
      chemicals) generally reflect only the last few hours (due to the fast
      equilibrium) of the weekly integrated samples obtained employing the high-volume
      sampler. This means that films and leaves can be usefully employed for predicting
      the short-term variability of low KOA organic contaminant air concentrations. 

PMID- 25844663
TI  - Spatial Accessibility to HIV Providers in Atlanta, Georgia.

PMID- 25844664
TI  - Shape-Dependent Multiexciton Emission and Whispering Gallery Modes in
      Supraparticles of CdSe/Multishell Quantum Dots.
AB  - Semiconductors are indispensable as the active light-emitting element in many
      optoelectronic devices. However, even the purest bulk semiconductors suffer from
      considerable nonradiative recombination leading to low photoluminescence
      efficiencies. Zero-dimensional quantum dots show a much better carrier-to-photon
      conversion caused by confinement of the excitons but suffer from nonradiative
      recombination when assembled into a solid, due to exciton energy transfer. Here,
      we report on the shape-dependent optical properties of self-assembled
      supraparticles composed of CdSe/multishell nanocrystals. All supraparticles show
      stable and bright photoluminescence in ambient up to high excitation intensities.
      When the supraparticles are deposited on a silicon surface their spherical shape
      is deformed due to drying. In addition to single-exciton emission, we observe
      bright emission from multiexciton states at high excitation powers. In contrast,
      supraparticles that retain their perfectly spherical shape show a spectrum with
      sharp Mie whispering gallery modes, while multiexciton emission is absent. 

PMID- 25844665
TI  - Preface: RECOMB/ISCB systems biology, regulatory genomics, and DREAM 2014 Special
      Issue.

PMID- 25844666
TI  - Multi-species network inference improves gene regulatory network reconstruction
      for early embryonic development in Drosophila.
AB  - Gene regulatory network inference uses genome-wide transcriptome measurements in
      response to genetic, environmental, or dynamic perturbations to predict causal
      regulatory influences between genes. We hypothesized that evolution also acts as
      a suitable network perturbation and that integration of data from multiple
      closely related species can lead to improved reconstruction of gene regulatory
      networks. To test this hypothesis, we predicted networks from temporal gene
      expression data for 3,610 genes measured during early embryonic development in
      six Drosophila species and compared predicted networks to gold standard networks
      of ChIP-chip and ChIP-seq interactions for developmental transcription factors in
      five species. We found that (i) the performance of single-species networks was
      independent of the species where the gold standard was measured; (ii) differences
      between predicted networks reflected the known phylogeny and differences in
      biology between the species; (iii) an integrative consensus network that
      minimized the total number of edge gains and losses with respect to all single
      species networks performed better than any individual network. Our results show
      that in an evolutionarily conserved system, integration of data from comparable
      experiments in multiple species improves the inference of gene regulatory
      networks. They provide a basis for future studies on the numerous multispecies
      gene expression datasets for other biological processes available in the
      literature. 

PMID- 25844668
TI  - A canonical correlation analysis-based dynamic bayesian network prior to infer
      gene regulatory networks from multiple types of biological data.
AB  - One of the challenging and important computational problems in systems biology is
      to infer gene regulatory networks (GRNs) of biological systems. Several methods
      that exploit gene expression data have been developed to tackle this problem. In
      this study, we propose the use of copy number and DNA methylation data to infer
      GRNs. We developed an algorithm that scores regulatory interactions between genes
      based on canonical correlation analysis. In this algorithm, copy number or DNA
      methylation variables are treated as potential regulator variables, and
      expression variables are treated as potential target variables. We first
      validated that the canonical correlation analysis method is able to infer true
      interactions in high accuracy. We showed that the use of DNA methylation or copy
      number datasets leads to improved inference over steady-state expression. Our
      results also showed that epigenetic and structural information could be used to
      infer directionality of regulatory interactions. Additional improvements in GRN
      inference can be gleaned from incorporating the result in an informative prior in
      a dynamic Bayesian algorithm. This is the first study that incorporates copy
      number and DNA methylation into an informative prior in dynamic Bayesian
      framework. By closely examining top-scoring interactions with different sources
      of epigenetic or structural information, we also identified potential novel
      regulatory interactions. 

PMID- 25844667
TI  - A scalable method for molecular network reconstruction identifies properties of
      targets and mutations in acute myeloid leukemia.
AB  - A key aim of systems biology is the reconstruction of molecular networks. We do
      not yet, however, have networks that integrate information from all datasets
      available for a particular clinical condition. This is in part due to the limited
      scalability, in terms of required computational time and power, of existing
      algorithms. Network reconstruction methods should also be scalable in the sense
      of allowing scientists from different backgrounds to efficiently integrate
      additional data. We present a network model of acute myeloid leukemia (AML). In
      the current version (AML 2.1), we have used gene expression data (both microarray
      and RNA-seq) from 5 different studies comprising a total of 771 AML samples and a
      protein-protein interactions dataset. Our scalable network reconstruction method
      is in part based on the well-known property of gene expression correlation among
      interacting molecules. The difficulty of distinguishing between direct and
      indirect interactions is addressed by optimizing the coefficient of variation of
      gene expression, using a validated gold-standard dataset of direct interactions.
      Computational time is much reduced compared to other network reconstruction
      methods. A key feature is the study of the reproducibility of interactions found
      in independent clinical datasets. An analysis of the most significant clusters,
      and of the network properties (intraset efficiency, degree, betweenness
      centrality, and PageRank) of common AML mutations demonstrated the biological
      significance of the network. A statistical analysis of the response of blast
      cells from 11 AML patients to a library of kinase inhibitors provided an
      experimental validation of the network. A combination of network and experimental
      data identified CDK1, CDK2, CDK4, and CDK6 and other kinases as potential
      therapeutic targets in AML. 

PMID- 25844669
TI  - Inferring genome-wide functional modulatory network: a case study on NF
      kappaB/RelA transcription factor.
AB  - How different pathways lead to the activation of a specific transcription factor
      (TF) with specific effects is not fully understood. We model context-specific
      transcriptional regulation as a modulatory network: triplets composed of a TF,
      target gene, and modulator. Modulators usually affect the activity of a specific
      TF at the posttranscriptional level in a target gene-specific action mode. This
      action may be classified as enhancement, attenuation, or inversion of either
      activation or inhibition. As a case study, we inferred, from a large collection
      of expression profiles, all potential modulations of NF-kappaB/RelA. The
      predicted modulators include many proteins previously not reported as physically
      binding to RelA but with relevant functions, such as RNA processing, cell cycle,
      mitochondrion, ubiquitin-dependent proteolysis, and chromatin modification.
      Modulators from different processes exert specific prevalent action modes on
      distinct pathways. Modulators from noncoding RNA, RNA-binding proteins, TFs, and
      kinases modulate the NF-kappaB/RelA activity with specific action modes
      consistent with their molecular functions and modulation level. The modulatory
      networks of NF-kappaB/RelA in the context epithelial-mesenchymal transition (EMT)
      and burn injury have different modulators, including those involved in
      extracellular matrix (FBN1), cytoskeletal regulation (ACTN1), and metastasis
      associated lung adenocarcinoma transcript 1 (MALAT1), a long intergenic
      nonprotein coding RNA, and tumor suppression (FOXP1) for EMT, and TXNIP, GAPDH,
      PKM2, IFIT5, LDHA, NID1, and TPP1 for burn injury. 

PMID- 25844670
TI  - Disease gene prioritization using network and feature.
AB  - Identifying high-confidence candidate genes that are causative for disease
      phenotypes, from the large lists of variations produced by high-throughput
      genomics, can be both time-consuming and costly. The development of novel
      computational approaches, utilizing existing biological knowledge for the
      prioritization of such candidate genes, can improve the efficiency and accuracy
      of the biomedical data analysis. It can also reduce the cost of such studies by
      avoiding experimental validations of irrelevant candidates. In this study, we
      address this challenge by proposing a novel gene prioritization approach that
      ranks promising candidate genes that are likely to be involved in a disease or
      phenotype under study. This algorithm is based on the modified conditional random
      field (CRF) model that simultaneously makes use of both gene annotations and gene
      interactions, while preserving their original representation. We validated our
      approach on two independent disease benchmark studies by ranking candidate genes
      using network and feature information. Our results showed both high area under
      the curve (AUC) value (0.86), and more importantly high partial AUC (pAUC) value
      (0.1296), and revealed higher accuracy and precision at the top predictions as
      compared with other well-performed gene prioritization tools, such as Endeavour
      (AUC-0.82, pAUC-0.083) and PINTA (AUC-0.76, pAUC-0.066). We were able to detect
      more target genes (9/18/19/27) on top positions (1/5/10/20) compared to Endeavour
      (3/11/14/23) and PINTA (6/10/13/18). To demonstrate its usability, we applied our
      method to a case study for the prediction of molecular mechanisms contributing to
      intellectual disability and autism. Our approach was able to correctly recover
      genes related to both disorders and provide suggestions for possible additional
      candidates based on their rankings and functional annotations. 

PMID- 25844671
TI  - cDREM: inferring dynamic combinatorial gene regulation.
AB  - Genes are often combinatorially regulated by multiple transcription factors
      (TFs). Such combinatorial regulation plays an important role in development and
      facilitates the ability of cells to respond to different stresses. While a number
      of approaches have utilized sequence and ChIP-based datasets to study
      combinational regulation, these have often ignored the combinational logic and
      the dynamics associated with such regulation. Here we present cDREM, a new method
      for reconstructing dynamic models of combinatorial regulation. cDREM integrates
      time series gene expression data with (static) protein interaction data. The
      method is based on a hidden Markov model and utilizes the sparse group Lasso to
      identify small subsets of combinatorially active TFs, their time of activation,
      and the logical function they implement. We tested cDREM on yeast and human data
      sets. Using yeast we show that the predicted combinatorial sets agree with other
      high throughput genomic datasets and improve upon prior methods developed to
      infer combinatorial regulation. Applying cDREM to study human response to flu, we
      were able to identify several combinatorial TF sets, some of which were known to
      regulate immune response while others represent novel combinations of important
      TFs. 

PMID- 25844672
TI  - The Cry of the Child and its Relationship to Hearing Loss in Parental Guardians
      and Health Care Providers.
AB  - In this study the authors investigate the sound pressure levels produced by
      crying children and discuss the possible adverse effects that direct exposure may
      impose on a tending guardian or healthcare professional. Sound intensity levels
      from various pediatric patients (N = 26) were measured under two segregate
      conditions, one imitating the exposure of an examining physician and the other
      resembling that of parental guardians. Interestingly, all of the recorded sound
      levels fell between 99-120 dB(A) of sound pressure; children presenting the
      greatest risk for intense cries with potentially harmful sound intensities were
      between the ages of 9 months and 6 years. The authors found that elevated noise
      levels produced from crying children can cause acute discomfort and mild pain to
      those exposed. In addition, there is a theoretical risk that chronic exposure to
      these intense sound pressures may result in noise-induced hearing loss in a
      parental guardian or an examining physician. Parents of young children may be
      more likely to succumb to impulsive reactions in attempting to arrest the crying,
      which could be a precipitating factor for child abuse, responding to physical
      stress as much as emotional stress. Social workers and medical personnel should
      consider suggesting the use of ear plugs by parental guardians of frequently
      crying children as a modality for the prevention of child abuse.

PMID- 25844673
TI  - A mixed phenotype of airway wall thickening and emphysema is associated with
      dyspnea and hospitalization for chronic obstructive pulmonary disease.
AB  - RATIONALE: Quantitative computed tomography (CT) has been used to phenotype
      patients with chronic obstructive pulmonary disease (COPD). A mixed phenotype is
      defined as the presence of both airway wall thickening and emphysema on
      quantitative CT. Little is known about patients with COPD with the mixed
      phenotype. OBJECTIVES: To propose a method of phenotyping COPD based on
      quantitative CT and to compare clinically relevant outcomes between patients with
      COPD with the mixed phenotype and those with other CT-based phenotypes. METHODS:
      Each of 427 male smokers (187 without COPD, 240 with COPD) underwent a complete
      medical interview, pulmonary function testing, and whole-lung CT on the same day.
      The percentage of low-attenuation volume at the threshold of -950 Hounsfield
      units (%LAV) and the square root of wall area of a hypothetical airway with an
      internal perimeter of 10 mm (Pi10) were measured. Patients with COPD were
      classified into four distinct phenotypes based on the upper limits of normal for
      %LAV and Pi10, which were derived from the data of smokers without COPD by using
      quantile regression. MEASUREMENTS AND MAIN RESULTS: Of 240 patients with COPD, 52
      (21.7%) were classified as CT-normal phenotype, 39 (16.3%) as airway-dominant
      phenotype, 103 (42.9%) as emphysema-dominant phenotype, and 46 (19.2%) as mixed
      phenotype. Patients with COPD with the mixed phenotype were associated with more
      severe dyspnea than those with each of the remaining CT-based phenotypes (P <
      0.01 for all comparisons). The number of hospitalizations for COPD exacerbations
      during the preceding year was 2.0 to 3.6 times higher in patients with the mixed
      phenotype than in those with each of the remaining CT-based phenotypes (P < 0.05
      for all comparisons). Findings persisted after adjustment for age, pack-years of
      smoking, smoking status, body mass index, and FEV1. CONCLUSIONS: Patients with
      COPD with the mixed phenotype are associated with more severe dyspnea and more
      frequent hospitalizations than those with each of the remaining CT-based
      phenotypes. Thus, patients with COPD with the mixed phenotype may need more
      attention and interventions.

PMID- 25844674
TI  - Metastatic carcinoma of unknown primary: diagnostic approach using
      immunohistochemistry.
AB  - Carcinoma of unknown primary origin (CUP) is one of the 10 most prevalent
      malignancies. CUP patients in whom a site of origin can be ascribed have better
      outcomes than those in which the primary tumor remains unidentified. Among the
      tools available to pathologists in approaching these lesions,
      immunohistochemistry is a reliable, inexpensive, and widely available resource.
      New markers continue to emerge, which, in combination with other historically
      useful antibodies, allow rapid and accurate identification of primary site in an
      increasing number of cases. This review discusses the approach to the diagnosis
      of CUP using immunohistochemistry and outlines some of the most useful markers
      with a particular focus on the utility of lineage-restricted transcription
      factors, including CDX2, NKX3-1, PAX8, SATB2, TTF-1, and SF1.

PMID- 25844675
TI  - Aggressive B-cell lymphomas: a review and practical approach for the practicing
      pathologist.
AB  - Recent advances in diffuse large B-cell lymphoma are changing the way
      pathologists approach, diagnose, and report on this heterogeneous group of
      lymphomas. The purpose of this review is to provide a practical yet comprehensive
      approach to diffuse large B-cell lymphoma and aggressive B-cell lymphomas that
      can be used and easily interpreted by pathologists at all levels of training. It
      will address important concepts and current testing modalities which provide
      important prognostic information for the clinician when considering appropriate
      chemotherapeutic regimens for each patient's lymphoma diagnosis. It will also
      provide some insights into recently reported signaling pathways and molecular
      alterations and their contribution to lymphomagenesis and how identifying these
      abnormalities may provide future potential therapeutic targets for these
      aggressive lymphomas.

PMID- 25844676
TI  - Clear cell proliferations of the skin.
AB  - Clear cell proliferations of the skin consist of a diverse group of lesions
      characterized by the presence of cells with abundant clear cytoplasm. They may
      arise from primary, metastatic, or non-neoplastic origins, with their distinctive
      cytoplasmic clearing attributable to causes ranging from artifact to accumulation
      of materials such as glycogen, mucin, or lipids. Despite the heterogeneity of
      these lesions, their distinguishing characteristics may be subtle, especially at
      high power. As such, histologic diagnosis can be challenging, and proper
      consideration relies on an understanding of the scope of possible origins,
      etiologies, and key immunohistochemical staining patterns of the various
      entities. This review categorizes cutaneous clear cell neoplasms by histogenesis,
      and offers differential diagnostic strategies to aid in their clinicopathologic
      evaluation.

PMID- 25844677
TI  - HER2 testing in gastric and gastroesophageal adenocarcinomas.
AB  - The human epidermal growth factor receptor 2 (HER2) is overexpressed in 10% to
      35% of gastric and gastroesophageal junction (GEJ) adenocarcinomas. In 2010, the
      phase III Trastuzumab for Gastric Cancer (ToGA) trial showed that addition of the
      anti-HER2 monoclonal antibody trastuzumab to chemotherapy significantly improved
      survival of patients with advanced or metastatic tumors that were positive for
      HER2 overexpression. As a result, HER2 testing is now recommended for all
      patients with advanced or metastatic disease, although there is still some debate
      as to the optimal methods of assessment. HER2 expression in gastric and GEJ
      tumors shows several differences compared with breast tumors and, for this
      reason, the proposed criteria for scoring HER2 expression in biopsies and
      resections of gastric and GEJ carcinomas differ from those used in breast
      carcinomas. This review discusses what is currently known about the patterns of
      HER2 expression in gastric and GEJ adenocarcinomas, summarizes the findings of
      the ToGA trial and its clinical implications, and provides an overview of the
      recommended guidelines for the most accurate evaluation of HER2 status in gastric
      and GEJ cancer.

PMID- 25844678
TI  - Intratubular germ cell neoplasia of the testis: a brief review.
AB  - Germ cell tumors of the testis may be divided into 3 broad categories according
      to age at presentation. The tumors in the pediatric age group include teratoma
      and yolk sac tumor. These tumors are generally not associated with convincing
      intratubular neoplasia. The second group consists of tumors presenting in third
      and fourth decade of life and include seminoma, embryonal carcinoma, yolk sac
      tumor, choriocarcinoma, and teratoma as well as mixed germ cell tumors. The
      precursor cell for these tumors is an abnormal gonocyte that fails to
      differentiate completely into spermatogonia. These abnormal cells stay dormant in
      the gonad during intrauterine life as well as infancy and childhood, but undergo
      proliferation during puberty and can be identified as intratubular germ cell
      neoplasia unclassified (IGCNU). These tumor cells continue to manifest protein
      expression pattern that resembles primitive germ cells (PLAP, c-KIT, OCT3/4).
      After a variable interval following puberty, IGCNU cells may acquire ability to
      penetrate the seminiferous tubules and present as an overt germ cell tumor.
      Acquisition of isochrome 12 and other genetic abnormalities are usually
      associated with this transition. The level of DNA methylation generally
      determines the phenotype of the germ cell tumor. The third type of germ cell
      tumors is spermatocytic seminoma, which is a rare tumor encountered later in life
      usually in fifth and sixth decade. The cell of origin of this tumor is probably
      postpubertal mature spermatogonia which acquire abnormal proliferative capability
      probably due to gain of chromosome 9 resulting in activation and amplification of
      genes such as DMRT1. The tumor cells manifest many of the proteins normally
      expressed by mature sperms such as VASA, SSX2, and occasionally OCT2. Although
      spermatocytic seminoma may also have an intratubular growth phase, it completely
      lacks features of IGCNU.

PMID- 25844679
TI  - A discussion of some advancements and some persistent difficulties in the
      recognition and understanding of the histopathologic and molecular features of
      selected odontogenic tumors and tumor-like malformations.
AB  - Overgrowths of epithelial, ectomesenchymal, and/or mesenchymal elements of the
      tooth-forming apparatus are quite variable with respect to their histopathologic
      characteristics and biological behaviors. Investigations of a variety of
      odontogenic lesions have led to an enhanced comprehension of many salient
      diagnostic features. This discussion provides an update with respect to the
      understanding of odontogenic tumors and tumor-like malformations and attempts to
      assist pathologists in the recognition and classification of these lesions.

PMID- 25844680
TI  - Selected case from the Arkadi M. Rywlin International Pathology Slide Club:
      carcinoma of the transverse colon in a young girl.
AB  - We report a case of a 14-year-old female with primary adenocarcinoma of the
      transverse colon. She was hospitalized after presenting with abdominal pain and
      signs of intestinal obstruction. There was no health antecedent or family history
      of neoplasia. Physical examination revealed a distended abdomen. Tenderness was
      elicited to palpation of the right lower quadrant. Magnetic resonance imaging of
      the abdomen revealed obstructive signs, with a constricting lesion in the mid
      transverse colon of probable neoplastic nature. Laparoscopic segmental resection
      of the colon was followed by standard right hemicolectomy. A circumferential mid
      transverse tumor was diagnosed as primary colorectal carcinoma (CRC) of signet
      ring cell type, AJCC stage IIIC, Dukes' C stage. On the basis of
      immunohistochemistry and clinical data, hereditary nonpolyposis and hamartomatous
      colorectal cancer syndromes were excluded. Involvement of either the p53, BRAF,
      or K-RAS genes was ruled out by immunohistochemistry profiling and genetic
      testing. The neoplasm was categorized as sporadic. The possibility of activation
      of the Wnt signaling pathway was suspected, because of a defective turnover of
      the beta-catenin protein. Postoperatively, the patient was treated with both
      systemic and intra-abdominal adjuvant chemotherapy, including oxaliplatin.
      Between 18 and 24 months after diagnosis, intra-abdominal tumor recurrences were
      detected. The patient underwent bilateral oophorectomies for Krukenberg tumors
      and received salvage chemotherapy. Recently, additional recurrent metastatic
      retroperitoneal disease caused hydronephrosis. The retroperitoneal mass was
      debulked and a ureteric stent was placed. At the time of this writing, 43 months
      after diagnosis, the patient is receiving FOLFOX chemotherapy combined with
      panitumumab. CRC of childhood is exceedingly rare, generally develops in the
      setting of unrecognized genetic predisposing factors to cancer, presents with
      advanced disease, is high grade, and tends to have dismal prognosis. 

PMID- 25844681
TI  - Low-level light/laser therapy versus photobiomodulation therapy.

PMID- 25844682
TI  - Clinical evaluation of the Er,Cr:YSGG Laser therapy in the treatment of denture
      related traumatic ulcerations: a randomized controlled clinical study.
AB  - OBJECTIVE: The aim of this study was to evaluate the efficacy of Er,Cr:YSGG laser
      irradiation in reducing pain and on healing rate of traumatic ulcerations (TU)
      during a 2-week period after placement of new complete dentures. BACKGROUND DATA:
      Denture-related TU are painful, and result in patient discomfort. Lasers are used
      in the treatment of different kinds of mucosal lesions; however, there are no
      published data available concerning the clinical outcome of the use of laser
      therapy in the treatment of TU. MATERIALS AND METHODS: Thirty edentulous patients
      with newly fabricated complete dentures who subsequently developed one or more
      pairs of TU participated in this study. For each patient, ulcerations were
      randomly assigned to the test and control groups. In the test group, ulcerations
      were irradiated with Er,Cr:YSGG laser. In the control group, the same laser
      without laser emission was used. Pain was assessed with a visual analog scale
      (VAS). Healing of ulcerations (HU) was graded by a clinician. RESULTS: In the
      test group, laser irradiation provided significantly reduced pain immediately
      after treatment, and provided a significant healing effect 1 day after treatment,
      and these effects were maintained throughout the study. In the control group,
      baseline VAS scores were not statistically significant at baseline and 1 day
      after treatment, and HU scores were statistically significant 3, 7, and 14 days
      after treatment. Intergroup comparisons revealed that the differences in VAS and
      HU scores were statistically significant for all time periods after treatment,
      except for day 14. CONCLUSIONS: Based on these findings, it may be concluded that
      Er,Cr:YSGG laser is effective in the treatment of TU.

PMID- 25844683
TI  - Real-time local experimental monitoring of the bleaching process.
AB  - OBJECTIVE: The purpose of this article was to investigate a new setup for tooth
      bleaching and monitoring of the same process in real time, so to prevent
      overbleaching and related sideeffects of the bleaching procedure. BACKGROUND
      DATA: So far, known bleaching procedures cannot simultaneously monitor and
      perform the bleaching process or provide any local control over bleaching.
      MATERIALS AND METHODS: The experimental setup was developed at the Institute of
      Physics, Zagreb. The setup consists of a camera, a controller, and optical
      fibers. The bleaching was performed with 25% hydrogen peroxide activated by
      ultraviolet light diodes, and the light for monitoring was emitted by white light
      diodes. The collected light was analyzed using a red-green-blue (RGB) index. A K
      type thermocouple was used for temperature measurements. Pastilles made from
      hydroxylapatite powder as well as human teeth served as experimental objects.
      RESULTS: Optimal bleaching time substantially varied among differently stained
      specimens. To reach reference color (A1, Chromascop shade guide), measured as an
      RGB index, bleaching time for pastilles ranged from 8 to >20 min, whereas for
      teeth it ranged from 3.5 to >20 min. The reflected light intensity of each R, G,
      and B component at the end of bleaching process (after 20 min) had increased up
      to 56% of the baseline intensity. CONCLUSIONS: The presented experimental setup
      provides essential information about when to stop the bleaching process to
      achieve the desired optical results so that the bleaching process can be
      completely responsive to the characteristics of every individual, leading to more
      satisfying results.

PMID- 25844684
TI  - Extraversion and the Rewarding Effects of Alcohol in a Social Context.
AB  - The personality trait of extraversion has been linked to problematic drinking
      patterns. Researchers have long hypothesized that such associations are
      attributable to increased alcohol-reward sensitivity among extraverted
      individuals, and surveys suggest that individuals high in extraversion gain
      greater mood enhancement from alcohol than those low in extraversion.
      Surprisingly, however, alcohol administration studies have not found individuals
      high in extraversion to experience enhanced mood following alcohol consumption.
      Of note, prior studies have examined extraverted participants-individuals who
      self-identify as being highly social-consuming alcohol in isolation. In the
      present research, we used a group drinking paradigm to examine whether
      individuals high in extraversion gained greater reward from alcohol than did
      those low in extraversion and, further, whether a particular social mechanism
      (partners' Duchenne smiling) might underlie alcohol reward sensitivity among
      extraverted individuals. Social drinkers (n 720) consumed a moderate dose of
      alcohol, placebo, or control beverage in groups of 3 over the course of 36 min.
      This social interaction was video-recorded, and Duchenne smiling was coded using
      the Facial Action Coding System. Results indicated that participants high in
      extraversion reported significantly more mood enhancement from alcohol than did
      those low in extraversion. Further, mediated moderation analyses focusing on
      Duchenne smiling of group members indicated that social processes fully and
      uniquely accounted for alcohol reward-sensitivity among individuals high in
      extraversion. Results provide initial experimental evidence that individuals high
      in extraversion experience increased mood-enhancement from alcohol and further
      highlight the importance of considering social processes in the etiology of
      alcohol use disorder.

PMID- 25844685
TI  - Malaria invasion ligand RH5 and its prime candidacy in blood-stage malaria
      vaccine design.
AB  - With drug resistance to available therapeutics continuing to develop against
      Plasmodium falciparum malaria, the development of an effective vaccine candidate
      remains a major research goal. Successful interruption of invasion of parasites
      into erythrocytes during the blood stage of infection will prevent the severe
      clinical symptoms and complications associated with malaria. Previously studied
      blood stage antigens have highlighted the hurdles that are inherent to this life
      cycle stage, namely that highly immunogenic antigens are also globally diverse,
      resulting in protection only against the vaccine strain, or that naturally
      acquired immunity to blood stage antigens do not always correlate with actual
      protection. The blood stage antigen reticulocyte binding homolog RH5 is essential
      for parasite viability, has globally limited diversity, and is associated with
      protection from disease. Here we summarize available information on this invasion
      ligand and recent findings that highlight its candidacy for inclusion in a blood
      stage malaria vaccine. 

PMID- 25844687
TI  - A Handling Study to Assess Use of the Respimat((r)) Soft MistTM Inhaler in
      Children Under 5 Years Old.
AB  - BACKGROUND: Respimat((r)) Soft Mist(TM) Inhaler (SMI) is a hand-held device that
      generates an aerosol with a high, fine-particle fraction, enabling efficient lung
      deposition. The study objective was to assess inhalation success among children
      using Respimat SMI, and the requirement for assistance by the parent/caregiver
      and/or a valved holding chamber (VHC). METHODS: This open-label study enrolled
      patients aged <5 years with respiratory disease and history of coughing and/or
      recurrent wheezing. Patients inhaled from the Respimat SMI (air only; no aerosol)
      using a stepwise configuration: "1" (dose released by child); "2" (dose released
      by parent/caregiver), and "3" (Respimat SMI with VHC, facemask, and
      parent/caregiver help). Co-primary endpoints included the ability to perform
      successful inhalation as assessed by the investigators using a standardized
      handling questionnaire and evaluation of the reasons for success. Inhalation
      profile in the successful handling configuration was verified with a
      pneumotachograph. Patient satisfaction and preferences were investigated in a
      questionnaire. RESULTS: Of the children aged 4 to <5 years (n=27) and 3 to <4
      years (n=30), 55.6% and 30.0%, respectively, achieved success without a VHC or
      help; with assistance, another 29.6% and 10.0%, respectively, achieved success,
      and the remaining children were successful with VHC. All children aged 2 to <3
      years (n=20) achieved success with the Respimat SMI and VHC. Of those aged <2
      years (n=22), 95.5% had successful handling of the Respimat SMI with VHC and
      parent/caregiver help. Inhalation flow profiles generally confirmed the outcome
      of the handling assessment by the investigators. Most parent/caregiver and/or
      child respondents were satisfied with operation, instructions for use, handling,
      and ease of holding the Respimat SMI with or without a VHC. CONCLUSIONS: The
      Respimat SMI is suitable for children aged <5 years; however, children aged <5
      years are advised to add a VHC to complement its use.

PMID- 25844688
TI  - Amelioration of bleomycin-induced pulmonary fibrosis in a mouse model by a
      combination therapy of bosentan and imatinib.
AB  - INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is characterized by alveolitis,
      progressing into fibrosis. Due to the involvement of both endothelin and platelet
      derived growth factor signaling in IPF, combination effects of a bosentan and
      imatinib were studied in mouse model of bleomycin-induced pulmonary fibrosis.
      METHODS: Mice subjected to bleomycin instillation (0.05 U) and were administered
      with either bosentan (100 mg/kg) and/or imatinib (50 mg/kg). Inflammatory cell
      count, total protein estimation in bronchoalveolar lavage fluid, lung edema,
      superoxide dismutase, catalase, myeloperoxidase activities, and Hematoxylin &
      Eosin staining were performed on day 7. Hydroxyproline content, alpha-smooth
      muscle actin (SMA), collagens I and III gene expression analysis,
      immunohistochemistry, matrix metalloproteinases-9 and -2 activities, trichrome
      and sirius red staining were performed on day 21. RESULTS: Combination treatment
      with bosentan and imatinib prevented bleomycin-induced mortality and loss of body
      weight more than the individual agents. On day 7, the combination therapy
      attenuated bleomycin-induced increase of total and differential inflammatory cell
      counts, total proteins, lung wet/dry weight ratio, myeloperoxidase activity, lung
      inflammatory cell infiltration more than individual agents alone. Bosentan but
      not imatinib ameliorated superoxide dismutase and catalase activities, which were
      lowered following bleomycin instillation. On day 21, combination therapy
      ameliorated bleomycin-induced increase of fibrosis score, collagen deposition,
      protein and gene expression of SMA, mRNA levels of collagens-I and -III, matrix
      metalloproteinase-9 and -2 activities more than monotherapy. CONCLUSION:
      Combination of bosentan and imatinib exerted more enhanced protection against
      bleomycin-induced inflammation and fibrosis than either of the agents alone.

PMID- 25844686
TI  - Circuit resistance training attenuates acute exertion-induced reductions in
      arterial function but not inflammation in obese women.
AB  - BACKGROUND: Cardiovascular disease (CVD) is a leading cause of preventable death
      among young women in the United States. Habitual resistance exercise training is
      known to have beneficial effects on endothelial function and CVD risk factors,
      including obesity; however, previous studies show that acute resistance exercise
      impairs endothelial function in obese adults who are sedentary, a response that
      may be linked to inflammation. We sought to determine if circuit-based resistance
      training (CRT) attenuates acute resistance exercise-induced reductions in
      endothelial function in a population of young, obese, sedentary women and whether
      or not inflammation plays a role in this response. METHODS: Eighteen obese [body
      mass index (BMI) 30.0-40.0 kg . m(-2)] young premenopausal women were randomly
      assigned to either a CRT group or a no-exercise control group (CON). Conduit
      artery endothelial function was assessed using brachial artery flow-mediated
      dilation (FMD) determined by ultrasound before and after a single bout of
      strenuous weightlifting (SWL). In addition, circulating inflammatory mediators
      (tumor necrosis factor-alpha and C-reactive protein), blood pressure, fasting
      blood lipids, glucose, waist circumference, body composition, and aerobic
      capacity were assessed. RESULTS: Among participants randomized to the CRT group,
      8 weeks of training led to considerable increases in FMD after SWL (P=0.001)
      compared to the CON group. However, no significant differences between the groups
      were observed in circulating inflammatory mediators, blood pressure, fasting
      blood lipids, or other physical and physiological characteristics. CONCLUSIONS:
      This study shows that CRT alleviates acute exertion-induced reductions in
      endothelial function among obese sedentary women in the absence of changes in
      inflammation.

PMID- 25844689
TI  - Attenuation of lipopolysaccharide-induced acute lung injury after (pro)renin
      receptor blockade.
AB  - PURPOSE/AIM: We performed a randomized, prospective animal study to investigate
      whether inhibiting the renin-angiotensin system with a (pro)renin receptor
      blocker (PRRB) prevents acute lung injury (ALI) in a rodent model. MATERIALS: We
      used Thirty-six male Sprague-Dawley rats. We administered lipopolysaccharide
      (LPS; 2 mg/kg) intratracheally with or without PRRB pretreatment (1 mg/kg/d).
      METHODS: We performed bronchoalveolar lavage (BAL) and lung removal at 4 h after
      LPS administration and measured levels of inflammatory cytokines, high mobility
      group box 1 (HMGB-1) protein, and total protein in bronchoalveolar lavage fluid
      (BALF). Myeloperoxidase (MPO) activity was detected in lung tissue homogenates
      using a sensitive ELISA. We performed hematoxylin and eosin staining and
      immunohistochemical staining for nonproteolytically activated prorenin in the
      left lung. RESULTS: The PRRB decreased leukocyte counts and total protein, tumor
      necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-2, IL-6, and IL-10 levels
      in the BALF and MPO activity in lung tissue. The PRRB reduced interstitial edema,
      hemorrhage, and the neutrophil count in the lung tissues. Consistent with the
      reduction in lung tissue damage, immunohistochemical staining showed that the
      PRRB decreased the amount of nonproteolytically activated prorenin. CONCLUSIONS:
      The PRRB blocked LPS-induced inflammatory response in the lung and protected
      against ALI. Therefore, it is a potential therapeutic agent for preventing ALI.

PMID- 25844690
TI  - Neuron-derived orphan receptor 1 promoted human pulmonary artery smooth muscle
      cells proliferation.
AB  - AIMS: As a transcription factor of the nuclear receptor superfamily, neuron
      derived orphan receptor 1 (NOR1) is induced rapidly in response to various
      extracellular stimuli. But, it is still unclear its role in pulmonary artery
      smooth muscle cells proliferation. MATERIALS AND METHODS: Human PASMCs were
      cultured in vitro and stimulated by serum. The special antisense
      oligodeoxynucleotides (AS-ODNs) were used to knockdown human NOR1 gene
      expression. Real-time PCR and Western-blot were used to evaluate the gene
      expression and protein levels. RESULTS: Fetal bovine serum (FBS) induced human
      PASMCs proliferation in a dose dependent manner. Furthermore, FBS promoted NOR1
      gene expression in a dose dependent manner and a time dependent manner. 10% FBS
      induced a maximal NOR1 mRNA levels at 2 h. FBS also induced a significant higher
      NOR1 protein levels as compared with control. The NOR1 over-expressed plasmid
      significantly promoted DNA synthesis and cells proliferation. Moreover, the
      special AS-ODNs against human NOR1 not only prevented NOR1 expression but also
      inhibited DNA synthesis and cells proliferation significantly. The NOR1 over
      expression plasmid could up-regulate cyclin D1 expression markedly, but the AS
      ODNs inhibited cyclin D1 expression significantly. CONCLUSION: So, we concluded
      that NOR1 could promote human PASMCs proliferation. Cyclin D1 might be involved
      in this process.

PMID- 25844691
TI  - Regional lung tissue changes with mechanical ventilation and fluid load.
AB  - PURPOSE: To investigate the regional gravity-dependent impact of mechanical
      ventilation and fluid overload on lung extracellular matrix (ECM) in healthy
      lungs. MATERIALS AND METHODS: The glycosaminoglycans (GAGs) composition of the
      ventral and dorsal lung parenchyma was determined in anesthetized supine healthy
      rats mechanically ventilated for 4 hours in air: (a) at low (~7.5 mL/kg) or high
      (~ 23 mL /kg) tidal volume (V(T)) and 0 cmH2O positive end-expiratory pressure
      (PEEP); (b) at low or high V(T) at 5 cmH2O PEEP and (c) with or without 7 mL
      /(kg.h) intravenous saline infusion. RESULTS: Mechanical ventilation degraded
      lung ECM, with alveolar septa thinning and structural GAGs disorganization. Low
      V(T) ventilation was associated with significant tissue structure changes in both
      ventral and dorsal lung regions, while high VT mainly affected the dependent
      ones. PEEP decreased ECM injury mainly in the ventral lung regions, although it
      did not prevent matrix fragmentation and washout at high V(T). Intravascular
      fluid load increased lung damage prevalently in the ventral lung regions.
      CONCLUSION: Mechanical ventilation and fluid load may cause additive injuries in
      healthy lungs, mainly in ventral regions.

PMID- 25844692
TI  - Pulmonary edema measured by MRI correlates with late-phase response to allergen
      challenge.
AB  - PURPOSE: Asthma is associated with reversible airway obstruction, leucocyte
      infiltration, airways hyperresponsiveness (AHR), and airways remodeling. Fluid
      accumulation causes pulmonary edema contributing to airways obstruction. We
      examined the temporal relationship between the late asthmatic response (LAR)
      following allergen challenge of sensitized guinea-pigs and pulmonary edema
      measured by magnetic resonance imaging (MRI). MATERIALS AND METHODS: Ovalbumin
      (OVA) sensitized guinea-pigs received either a single OVA inhalation (acute) or
      nine OVA inhalations at 48 h intervals (chronic). Airways obstruction was
      measured as specific airways conductance (sG(aw)) by whole body plethysmography.
      AHR to inhaled histamine and bronchoalveolar lavage for leucocyte counts were
      measured 24 h after a single or the final chronic ovalbumin challenges. MRI was
      performed at intervals after OVA challenge and high-intensity edemic signals were
      quantified. RESULTS: Ovalbumin caused early bronchoconstriction, followed at 7 h
      by an LAR and at 24 h AHR and leucocyte influx. The bright-intensity MRI edema
      signal, peaking at 7 h, was significantly (P < .05) greater after chronic (9.0 +/
      0.7 * 10(3) mm(3)) than acute OVA (7.6 +/- 0.2 * 10(3) mm(3)). Dexamethasone
      treatment before acute OVA abolished the AHR and LAR and significantly reduced
      eosinophils and the bright-intensity MRI edema from 9.1 +/- 1.0 to 6.4 +/- 0.3 *
      10(3) mm(3). CONCLUSION: We show a temporal relationship between edema and the
      LAR and their parallel reduction, along with eosinophils and AHR, by
      dexamethasone. This suggests a close causative association between pulmonary
      edema and impaired airways function.

PMID- 25844694
TI  - Early Head CT Findings Are Associated With Outcomes After Pediatric Out-of
      Hospital Cardiac Arrest.
AB  - OBJECTIVES: Head CT after out-of-hospital cardiac arrest is often obtained to
      evaluate intracranial pathology. Among children admitted to the PICU following
      pediatric out-of-hospital cardiac arrest, we hypothesized that loss of gray-white
      matter differentiation and basilar cistern and sulcal effacement are associated
      with mortality and unfavorable neurologic outcome. DESIGN: Retrospective, cohort
      study. SETTING: Single, tertiary-care center PICU. PATIENTS: Seventy-eight
      patients less than 18 years old who survived out-of-hospital cardiac arrest to
      PICU admission and had a head CT within 24 hours of return of spontaneous
      circulation were evaluated from July 2005 through May 2012. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: Median time to head CT from return of spontaneous
      circulation was 3.3 hours (1.0, 6.0). Median patient age was 2.3 years (0.4,
      9.5). Thirty-nine patients (50%) survived, of whom 29 (74%) had favorable
      neurologic outcome. Nonsurvivors were more likely than survivors to have 1) loss
      of gray-white matter differentiation (Hounsfield unit ratios, 0.96 [0.88, 1.07]
      vs 1.1 [1.07, 1.2]; p < 0.001), 2) basilar cistern effacement (93% vs 7%; p =
      0.001; positive predictive value, 94%; negative predictive value, 59%), and 3)
      sulcal effacement (100% vs 0%; p <= 0.001; positive predictive value, 100%;
      negative predictive value, 68%). All patients with poor gray-white matter
      differentiation or sulcal effacement had unfavorable neurologic outcomes. Only
      one patient with basilar cistern effacement had favorable outcome. CONCLUSIONS:
      Loss of gray-white matter differentiation and basilar cistern effacement and
      sulcal effacement are associated with poor outcome after pediatric out-of
      hospital cardiac arrest. Select patients may have favorable outcomes despite
      these findings.

PMID- 25844695
TI  - HIV Infection and Linkage to HIV-Related Medical Care in Large Urban Areas in the
      United States, 2009.
AB  - BACKGROUND: Residents of urban areas have accounted for the majority of persons
      diagnosed with HIV disease in the United States. Linking persons recently
      diagnosed with HIV to primary medical care is an important indicator in the
      National HIV/AIDS Strategy. METHODS: We analyzed data reported to the HIV
      Surveillance System in 18 urban areas in the United States. Standardized
      executable SAS programs were distributed to determine the number of HIV cases
      living through 2008, number of HIV cases diagnosed in 2009, and the percentage of
      those diagnosed in 2009 who had reported CD4 lymphocyte or HIV viral load test
      results within 3 months of HIV diagnosis. Data were presented by jurisdiction,
      age group at diagnosis, race/ethnicity, sex at birth, birth country, disease
      stage, and transmission category. RESULTS: By jurisdiction, the percentage of
      persons diagnosed in 2009 with at least 1 CD4 or HIV viral load test within 3
      months of diagnosis ranged from 48.5% to 92.5% (median: 70.9). The percentage of
      persons linked to care varied by age group and by racial/ethnic groups. Fourteen
      of the 18 areas reported that the percentage of persons linked to care was
      greater than 65%, the baseline measure indicated in the National HIV/AIDS
      Strategy. CONCLUSIONS: A wide range in percent linked to HIV medical care was
      observed between residents of 18 urban areas in the United States with noted age
      and racial disparities. Routine testing and linkage efforts and intensified
      prevention efforts should be considered to increase access to primary HIV-related
      medical care.

PMID- 25844693
TI  - Age influences inflammatory responses, hemodynamics, and cardiac proteasome
      activation during acute lung injury.
AB  - BACKGROUND: Acute lung injury (ALI) is a significant source of morbidity and
      mortality in critically ill patients. Age is a major determinant of clinical
      outcome in ALI. The increased ALI-associated mortality in the older population
      suggests that there are age-dependent alterations in the responses to pulmonary
      challenge. The objective of this observational study was to evaluate age
      dependent differences in the acute (within 6 hours) immunological and
      physiological responses of the heart and lung, to pulmonary challenge, that could
      result in increased severity. METHODS: Male C57Bl/6 mice (young: 2-3 months, old:
      18-20 months) were challenged intratracheally with cell wall components from Gram
      positive bacteria (lipoteichoic acid and peptidoglycan). After 6 hours, both
      biochemical and physiological consequences of the challenge were assessed.
      Alveolar infiltration of inflammatory cells and protein, airspace and blood
      cytokines, cardiac function and myocardial proteasome activity were determined.
      RESULTS: In young mice, there was a dose-dependent response to pulmonary
      challenge resulting in increased airspace neutrophil counts, lung permeability,
      and concentrations of cytokines in bronchoalveolar lavage fluid and plasma. A
      midrange dose was then selected to compare the responses in young and old
      animals. In comparison, the old animals displayed increased neutrophil
      accumulation in the airspaces, decreased arterial oxygen saturation, body
      temperatures, plasma cytokine concentrations, and a lack of myocardial proteasome
      response, following challenge. CONCLUSIONS: Age-dependent differences in the
      onset of systemic response and in maintenance of vital functions, including
      temperature control, oxygen saturation, and myocardial proteasome activation, are
      evident. We believe a better understanding of these age-related consequences of
      ALI can lead to more appropriate treatments in the elderly patient population.

PMID- 25844696
TI  - A Population-Level Evaluation of the Effect of Antiretroviral Therapy on Cancer
      Incidence in Kyadondo County, Uganda, 1999-2008.
AB  - BACKGROUND: The introduction of antiretroviral therapy (ART) in the United States
      and Europe has led to changes in the incidence of cancers among HIV-infected
      persons, including dramatic decreases in Kaposi sarcoma and non-Hodgkin lymphoma,
      and increases in Hodgkin lymphoma, liver, and anogenital malignancies. We sought
      to evaluate whether increasing availability of ART is associated with changing
      cancer incidence in Uganda. METHODS: Incident cases of 10 malignancies were
      identified from Kampala Cancer Registry from 1999 to 2008. ART coverage rates for
      Uganda were abstracted from the Joint United Nations Program on HIV/AIDS reports.
      Negative binomial and Poisson regression modeled the association between ART
      coverage and age-adjusted cancer incidence. RESULTS: ART coverage in Uganda
      increased from 0% to 43% from 1999 to 2008. With each 10% increase in ART
      coverage, incidence of Kaposi sarcoma decreased by 5% [incidence rate ratio (IRR)
      = 0.95, 95% confidence interval: 0.91 to 0.99, P = 0.02] and stomach cancer
      decreased by 13% [IRR = 0.87 (95% CI: 0.80 to 0.95), P = 0.002]. Conversely,
      incidence of non-Hodgkin lymphoma increased by 6% [IRR = 1.06 (95% CI: 1 to
      1.12), P = 0.05], liver cancer by 12% [IRR = 1.12 (95% CI: 1.04 to 1.21), P =
      0.002], prostate cancer by 5% [IRR = 1.05 (95% CI: 1 to 1.10), P = 0.05], and
      breast cancer by 5% [IRR = 1.05 (95% CI: 1 to 1.11), P = 0.05]. ART coverage was
      not associated with incidence of invasive cervical cancer, lung, colon, and
      Hodgkin disease. These findings were similar when restricted to histologically
      confirmed cases. CONCLUSIONS: Our findings suggest that AIDS-defining
      malignancies and other malignancies are likely to remain significant public
      health burdens in sub-Saharan Africa even as ART availability increases.

PMID- 25844697
TI  - CMV Retinitis Diagnosis by Non-ophthalmologists: Learning Curve Over a 4-Day
      Training Workshop.

PMID- 25844698
TI  - Metabolic Profiling of Children Undergoing Surgery for Congenital Heart Disease.
AB  - OBJECTIVE: Inflammation and metabolism are closely interlinked. Both undergo
      significant dysregulation following surgery for congenital heart disease,
      contributing to organ failure and morbidity. In this study, we combined cytokine
      and metabolic profiling to examine the effect of postoperative tight glycemic
      control compared with conventional blood glucose management on metabolic and
      inflammatory outcomes in children undergoing congenital heart surgery. The aim
      was to evaluate changes in key metabolites following congenital heart surgery and
      to examine the potential of metabolic profiling for stratifying patients in terms
      of expected clinical outcomes. DESIGN: Laboratory and clinical study. SETTING:
      University Hospital and Laboratory. PATIENTS: Of 28 children undergoing surgery
      for congenital heart disease, 15 underwent tight glycemic control postoperatively
      and 13 were treated conventionally. INTERVENTIONS: Metabolic profiling of blood
      plasma was undertaken using proton nuclear magnetic resonance spectroscopy. A
      panel of metabolites was measured using a curve-fitting algorithm. Inflammatory
      cytokines were measured by enzyme-linked immunosorbent assay. The data were
      assessed with respect to clinical markers of disease severity (Risk Adjusted
      Congenital heart surgery score-1, Pediatric Logistic Organ Dysfunction, inotrope
      score, duration of ventilation and pediatric ICU-free days). MEASUREMENTS AND
      MAIN RESULTS: Changes in metabolic and inflammatory profiles were seen over the
      time course from surgery to recovery, compared with the preoperative state. Tight
      glycemic control did not significantly alter the response profile. We identified
      eight metabolites (3-D-hydroxybutyrate, acetone, acetoacetate, citrate, lactate,
      creatine, creatinine, and alanine) associated with surgical and disease severity.
      The strength of proinflammatory response, particularly interleukin-8 and
      interleukin-6 concentrations, inversely correlated with PICU-free days at 28
      days. The interleukin-6/interleukin-10 ratio directly correlated with plasma
      lactate. CONCLUSIONS: This is the first report on the metabolic response to
      cardiac surgery in children. Using nuclear magnetic resonance to monitor the
      patient journey, we identified metabolites whose concentrations and trajectory
      appeared to be associated with clinical outcome. Metabolic profiling could be
      useful for patient stratification and directing investigations of clinical
      interventions.

PMID- 25844699
TI  - Xenon Protects Against Septic Acute Kidney Injury via miR-21 Target Signaling
      Pathway.
AB  - OBJECTIVES: Septic acute kidney injury is one of the most common and life
      threatening complications in critically ill patients, and there is no approved
      effective treatment. We have shown xenon provides renoprotection against ischemia
      reperfusion injury and nephrotoxicity in rodents via inhibiting apoptosis. Here,
      we studied the effects of xenon preconditioning on septic acute kidney injury and
      its mechanism. DESIGN: Experimental animal investigation. SETTING: University
      research laboratory. SUBJECTS: Experiments were performed with male C57BL/6 mice,
      10 weeks of age, weighing 20-25 g. INTERVENTIONS: We induced septic acute kidney
      injury by a single intraperitoneal injection of Escherichia coli
      lipopolysaccharide at a dose of 20 mg/kg. Mice were exposed for 2 hours to either
      70% xenon or 70% nitrogen, 24 hours before the onset of septic acute kidney
      injury. In vivo knockdown of miR-21 was performed using locked nucleic acid
      modified anti-miR, the role of miR-21 in renal protection conferred by the xenon
      preconditioning was examined, and miR-21 signaling pathways were analyzed.
      MEASUREMENTS AND MAIN RESULTS: Xenon preconditioning provided morphologic and
      functional renoprotection, characterized by attenuation of renal tubular damage,
      apoptosis, and a reduction in inflammation. Furthermore, xenon treatment
      significantly upregulated the expression of miR-21 in kidney, suppressed
      proinflammatory factor programmed cell death protein 4 expression and nuclear
      factor-kappaB activity, and increased interleukin-10 production. Meanwhile, xenon
      preconditioning also suppressed the expression of proapoptotic protein
      phosphatase and tensin homolog deleted on chromosome 10, activating protein
      kinase B signaling pathway, subsequently increasing the expression of
      antiapoptotic B-cell lymphoma-2, and inhibiting caspase-3 activity. Knockdown of
      miR-21 upregulated its target effectors programmed cell death protein 4 and
      phosphatase and tensin homolog deleted on chromosome 10 expression, resulted in
      an increase in apoptosis, and exacerbated lipopolysaccharide-induced acute kidney
      injury. CONCLUSION: Our findings demonstrated that xenon preconditioning
      protected against lipopolysaccharide-induced acute kidney injury via activation
      of miR-21 target signaling pathways.

PMID- 25844700
TI  - Radial Artery Applanation Tonometry for Continuous Noninvasive Cardiac Output
      Measurement: A Comparison With Intermittent Pulmonary Artery Thermodilution in
      Patients After Cardiothoracic Surgery.
AB  - OBJECTIVES: Radial artery applanation tonometry allows completely noninvasive
      continuous cardiac output estimation. The aim of the present study was to compare
      cardiac output measurements obtained with applanation tonometry (AT-CO) using the
      T-Line system (Tensys Medical, San Diego, CA) with cardiac output measured by
      intermittent pulmonary artery thermodilution using a pulmonary artery catheter
      (PAC-CO) with regard to accuracy, precision of agreement, and trending ability.
      DESIGN: A prospective method comparison study. SETTING: The study was conducted
      in a cardiosurgical ICU of a German university hospital. PATIENTS: We performed
      cardiac output measurements in 50 patients after cardiothoracic surgery.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Three independent sets of
      three consecutive thermodilution measurements (i.e., PAC-CO) each were performed
      per patient, and AT-CO was measured simultaneously. The average of the three
      thermodilution cardiac output measurements was compared with the average of the
      corresponding three AT-CO values resulting in 150 paired cardiac output
      measurements. In 13 patients, cardiac output-modifying maneuvers performed for
      clinical reasons additionally allowed to evaluate trending ability. For
      statistical analysis, we used Bland-Altman analysis, the percentage error, four
      quadrant plot, and concordance analysis. Mean PAC-CO was 4.7 +/- 1.2 L/min and
      mean AT-CO was 4.9 +/- 1.1 L/min. The mean of differences was -0.2 L/min with 95%
      limits of agreement of -1.8 to + 1.4 L/min. The percentage error was 34%. The
      concordance rate was 95%. CONCLUSIONS: Continuous cardiac output measurement
      using the noninvasive applanation tonometry technology is basically feasible in
      ICU patients after cardiothoracic surgery. The applanation tonometry technology
      provides cardiac output values with reasonable accuracy and precision of
      agreement compared with intermittent pulmonary artery thermodilution measurements
      in a clinical study setting and is able to reliably track cardiac output changes
      induced by cardiac output-modifying maneuvers.

PMID- 25844701
TI  - Postoperative Functional Evaluation of Percutaneous Vertebroplasty Compared With
      Percutaneous Kyphoplasty for Vertebral Compression Fractures.
AB  - Both percutaneous vertebroplasty (PVP) and percutaneous kyphoplasty (PKP) have
      shown their superiorities in the treatment of vertebral compression fractures
      (VCFs), yet, few studies have compared their postoperative functional outcomes in
      patients with VCFs; the authors therefore conducted this meta-analysis to explore
      the postoperative functional recovery efficacies of PVP and PKP in the treatment
      of VCFs. Computerized bibliographic databases were applied to identify relevant
      articles comparing the therapeutic effect of PVP and PKP in the treatment of
      VCFs. Standardized mean difference and its 95% confidence interval were
      calculated. Statistical analyses were conducted with the STATA statistical
      software. Postoperative Oswestry Disability Index investigation outcomes revealed
      a significant difference between the PVP group and PKP group. Subgroup analysis
      by the 8 dimensions of the SF-36 health survey presented a statistical
      significance in general health between the PVP group and PKP group. The
      application of PKP has the superiority in postoperative functional recovery of
      VCFs as compared with PVP, especially in efficaciously extending kyphosis angle,
      improving vertebral body height and decreasing complication rate.

PMID- 25844702
TI  - In situ medical simulation investigation of emergency department procedural
      sedation with randomized trial of experimental bedside clinical process guidance
      intervention.
AB  - INTRODUCTION: Patient safety during emergency department procedural sedation
      (EDPS) can be difficult to study. Investigators sought to delineate and
      experimentally assess EDPS performance and safety practices of senior-level
      emergency medicine residents through in situ simulation. METHODS: Study sessions
      used 2 pilot-tested EDPS scenarios with critical action checklists, institutional
      forms, embedded probes, and situational awareness questionnaires. An experimental
      informatics system was separately developed for bedside EDPS process guidance.
      Postgraduate year 3 and 4 subjects completed both scenarios in randomized order;
      only experimental subjects were provided with the experimental system during
      second scenarios. RESULTS: Twenty-four residents were recruited into a control
      group (n = 12; 6.2 +/- 7.4 live EDPS experience) and experimental group (n = 12;
      11.3 +/- 8.2 live EDPS experience [P = 0.10]). Critical actions for EDPS
      medication selection, induction, and adverse event recognition with resuscitation
      were correctly performed by most subjects. Presedation evaluations, sedation
      rescue preparation, equipment checks, time-outs, and documentation were
      frequently missed. Time-outs and postsedation assessments increased during second
      scenarios in the experimental group. Emergency department procedural sedation
      safety probe detection did not change across scenarios in either group.
      Situational awareness scores were 51% +/- 7% for control group and 58% +/- 12%
      for experimental group. Subjects using the experimental system completed more
      time-outs and scored higher Simulation EDPS Safety Composite Scores, although
      without comprehensive improvements in EDPS practice or safety. CONCLUSIONS: Study
      simulations delineated EDPS and assessed safety behaviors in senior emergency
      medicine residents, who exhibited the requisite medical knowledge base and
      procedural skill set but lacked some nontechnical skills that pertain to
      emergency department microsystem functions and patient safety. The experimental
      system exhibited limited impact only on in-simulation time-out compliance.

PMID- 25844703
TI  - Syphilis among adolescents and young adults in Cincinnati, Ohio: testing,
      infection and characteristics of youth with syphilis infection.
AB  - Little is known about the epidemiology of syphilis among adolescents and young
      adults. This study examined, among more than 17000 young people aged 13-22 years
      old, trends in rates of syphilis testing and infection; characteristics of
      infected adolescents; and agreement about syphilis staging and treatment between
      provider and chart reviewer. Rates of syphilis testing increased but rates of
      syphilis infection did not increase significantly over a 5-year period. A
      majority of infected men reported only opposite-sex sexual contact. High
      agreement between providers and chart reviewers was found. These findings
      demonstrate the need for complete assessment of risk factors and use of local
      epidemiology in screening practices. 

PMID- 25844704
TI  - Transcutaneous Electrical Nerve Stimulation Increases Rectal Activity in
      Children.
AB  - OBJECTIVES: Neurostimulation is increasingly used in treating bladder and bowel
      dysfunction, but its effect on rectal motility is obscure. The aim of the study
      was to evaluate the acute effect of transcutaneous electrical nerve stimulation
      (TENS) on rectal motility in children with overactive bladder (OAB). METHODS: In
      this double-blind placebo-controlled study in 20 children with OAB (mean age 8.6
      +/- 1.8 years; 7 girls), 48-hour urodynamic monitoring including rectal manometry
      was performed. After 24-hours of baseline investigation without stimulation the
      children were randomised to either active TENS (n = 10) or placebo (n = 10).
      Surface electrodes were placed over the sacral bone. The exterior of active and
      placebo stimulators was identical. Starting in the morning, the children received
      either continuous TENS stimulation or placebo until bedtime. Rectal contractions
      were de&filig;ned as pressure runs exceeding 5 cm H2O and lasting >=3 minutes.
      RESULTS: At baseline there was no significant difference in proportion of time
      with rectal contractions in the 2 groups (TENS group median 31% [range 12%-66%]
      vs placebo group median 31% [range 10%-66%]; P = 0.75); however, on the day of
      stimulation there was more time with rectal contractions in the group receiving
      TENS (median 51% [range 25%-78%]) compared with placebo (median 32% [range 4%
      68%]; P = 0.02). Also, there was an increase in time with rectal contractions in
      the TENS group (P = 0.007) but not in the placebo group (P = 0.39). The night
      after the TENS was disabled, rectal activity in both groups returned to baseline
      level. CONCLUSIONS: TENS acutely increases time with rectal contractions in
      children undergoing urodynamic investigation. The effect disappears when the
      stimulator is turned off.

PMID- 25844706
TI  - Effects of Amoxicillin and Clavulanic Acid on the Spontaneous Mechanical Activity
      of Juvenile Rat Duodenum.
AB  - OBJECTIVES: There are a limited number of medications for the treatment of
      foregut dysmotility. Enteral amoxicillin/clavulanic acid induces phase III
      duodenal contractions in a fasting pediatric patient. The mechanism by which this
      occurs is unknown. We examined the individual contributions of amoxicillin and
      clavulanic acid on the spontaneous mechanical activity of juvenile rat duodenum
      to better understand this phenomenon. METHODS: Duodenal segments from juvenile
      rats were longitudinally attached to force transducers in organ baths. Samples
      were cumulatively exposed to amoxicillin or clavulanic acid. Separate samples
      were exposed to carbachol alone to assess response in both the presence and
      absence of amoxicillin or clavulanic acid. Basal tone, frequency, and amplitude
      of contractions were digitized and recorded. RESULTS: The amplitude of the
      spontaneous contractions increased with amoxicillin. Inhibition of neuronal
      activity prevented this effect. Clavulanic acid did not affect the spontaneous
      contractions. Basal tone and the rate of contractions did not differ with either
      drug. Stimulation with carbachol in the presence of amoxicillin caused a
      statistically significant increase in the contractility compared with carbachol
      alone. CONCLUSIONS: Amoxicillin alters the spontaneous longitudinal mechanical
      activity of juvenile rat duodenum. Our results suggest that amoxicillin modulates
      the spontaneous pattern of cyclic mechanical activity of duodenal smooth muscle
      through noncholinergic, neurally mediated mechanisms. Our work provides an
      initial physiologic basis for the therapeutic use of amoxicillin in patients with
      gastrointestinal dysmotility.

PMID- 25844707
TI  - An Opinion on "Staging" of Infant Formula: A Developmental Perspective on Infant
      Feeding.
AB  - Breast milk is a dynamic fluid with compositional changes occurring throughout
      the period of lactation. Some of these changes in nutrient concentrations reflect
      the successively slowing growth rate and developmental changes in metabolic
      requirements that infants undergo during the first year of life. Infant formula,
      in contrast, has a static composition, intended to meet the nutritional
      requirements of infants from birth to 6 or 12 months of age. To better fit the
      metabolic needs of infants and to avoid nutrient limitations or excesses, we
      suggest that infant formulas should change in composition with the age of the
      infant, that is, different formulas are created/used for different ages during
      the first year of life. We propose that specific formulas for 0 to 3 months
      (stage 1), 3 to 6 months (stage 2), and 6 to 12 months (stage 3) of age may be
      nutritionally and physiologically advantageous to infants. Although this
      initially may impose some difficult practical/conceptual issues, we believe that
      this staging concept would improve nutrition of formula-fed infants and,
      ultimately, improve outcomes and make their performance more similar to that of
      breast-fed infants. 

PMID- 25844708
TI  - Threonine Requirement of the Enterally Fed Term Infant in the First Month of
      Life.
AB  - OBJECTIVE: Threonine is one of the essential amino acids. Its major fate is
      incorporation into intestinal mucosal proteins and synthesis of secretory
      glycoproteins. Therefore, it has an important function in the neonatal gut
      barrier integrity. The objective was to quantify the threonine requirement in
      fully enterally fed term neonates by means of the indicator amino acid oxidation
      (IAAO) method, using L-[1-C]phenylalanine as indicator. METHODS: After a 24-hour
      test diet adaptation, containing randomly assigned amounts of threonine (range 5
      182 mg . kg . day), the participating neonates received a primed continuous
      infusion of [C]bicarbonate and L-[1-C]phenylalanine. At baseline and during the
      plateau phase of both infusions, breath samples were obtained for CO2. The
      fractional L-[1-C]phenylalanine oxidation (FCO2) was estimated and plotted
      against the threonine intakes. Biphasic linear regression crossover analysis was
      used to calculate the breakpoint of the FCO2, representing the mean threonine
      requirement. Data are presented as mean +/- SD. RESULTS: Thirty-two term neonates
      (gestational age 39 +/- 1 weeks, birth weight 3.3 +/- 0.3 kg, mean postnatal age
      10 +/- 4 days) were studied. The mean threonine requirement was estimated to be
      68 mg . kg . day with an upper and lower 95% confidence interval of 104 and 32 mg
      . kg . day, respectively (r = 0.37). CONCLUSIONS: The determined threonine
      requirement is extremely close to the existing requirement recommendations (~90%
      of the present World Health Organization requirement guidelines). Infant formula
      preparations presently on the market, however, contain up to twice as much
      threonine as recommended. The threonine intake in formula-fed infants may
      therefore be reduced considerably.

PMID- 25844709
TI  - Safety of a New Amino Acid Formula in Infants Allergic to Cow's Milk and
      Intolerant to Hydrolysates.
AB  - OBJECTIVES: Amino acid-based formulas (AAFs) are recommended for children with
      cow's-milk allergy (CMA) failing to respond to extensively hydrolysed formulas
      (eHFs). We evaluated the effects of a new thickened AAF (TAAF, Novalac),
      containing a pectin-based thickener, and a reference AAF (RAAF, Neocate) on
      allergy symptoms and safety, through blood biochemistry analysis and growth.
      METHODS: Infants (ages < 18 months) with CMA symptoms failing to respond to eHFs
      were randomised in a double-blind manner to receive TAAF or RAAF for 3 months.
      All of the infants were then fed TAAF for 3 additional months. Paediatric visits
      occurred at 1, 3, and 6 months. Blood samples were collected at inclusion and 3
      months. RESULTS: Results at 1 month were previously described. The 75 infants
      with proven CMA and eHF intolerance tolerated their allocated formula. At 3
      months, the dominant allergic symptom had disappeared in 76.2% of the infants
      with TAAF and in 51.5% of the infants with RAAF (P = 0.026). The Scoring Atopic
      Dermatitis Index significantly improved more with TAAF than with RAAF (-27.3 +/-
      2.3 vs -20.8 +/- 2.2, P = 0.048). Of the infants, 92.9% had normal stools (soft
      or formed consistency) with TAAF vs 75.8% with RAAF (P = 0.051). More infants in
      TAAF group had better quality of nighttime sleep (P = 0.036) and low frequency of
      irritability signs (P < 0.001). With both formulas, all of the biochemical
      parameters were within normal ranges. There were no differences between the 2
      groups in any of the anthropometric z scores. CONCLUSIONS: The new TAAF was
      tolerated by all of the infants with CMA and intolerance to eHFs. Anthropometric
      and clinical data showed that both formulas were safe.

PMID- 25844710
TI  - Endoscopic Incision for the Treatment of Refractory Esophageal Anastomotic
      Strictures in Children.
AB  - OBJECTIVES: The aim of the present study was to assess the safety and efficacy of
      endoscopic incision (EI) for the treatment of refractory anastomotic esophageal
      strictures in pediatric patients. METHODS: We retrospectively reviewed the
      medical records of pediatric patients with refractory anastomotic strictures
      after surgical repair of esophageal atresia who underwent >=3 sessions of
      endoscopic treatments (dilation and/or stenting). They were treated with EI alone
      or together with esophageal stenting. Efficacy and safety were evaluated during
      periodical follow-up. RESULTS: All of the 7 children received the procedure
      successfully with the operation time of 15 to 60 minutes. Four of them received
      EI alone, whereas the other 3 received EI with esophageal stenting (EIES). The
      symptoms remitted in all of the patients, and the dysphagia score decreased from
      3-4 to 0-1 during follow-up from 1 to 21 months. The average diameter of
      stricture was enlarged from 3 mm (range 2-5 mm) to 10.6 mm (range 8-12 mm). One
      patient suffered from chest pain, which resolved within 3 days. Patient 1 had
      recurrence 11 months after EIES, and patient 6 had recurrence 3 months after EI.
      They all underwent an additional EI to maintain patency. No severe complications
      were observed during operation and periodical follow-up. CONCLUSIONS: EI is safe
      and appears effective for refractory esophageal anastomotic strictures in
      children in the short term. Large comparative studies are warranted to further
      confirm our findings. The long-term follow-up is necessary for assessing the long
      term efficacy of the new technique.

PMID- 25844711
TI  - Importance of Physical Examination: Occult Blood and Perianal Examination in
      Screening for Pediatric Inflammatory Bowel Disease.

PMID- 25844712
TI  - Bile Acids as Biomarkers: Liver and Gut Cross Talk in NAFLD.

PMID- 25844714
TI  - What tumours should we treat with focal therapy based on risk category, grade,
      size and location?
AB  - PURPOSE OF REVIEW: Focal therapy aims to reduce side-effects of active whole
      gland therapies with an acceptable or noninferior oncologic benefit for the
      patient. The definition of the lesion to treat using this tissue-preserving
      approach is central, and there is a recent shift in considering more aggressive
      disease than in the past. This article examines recent consensus reports,
      assessment of emerging techniques, histologic considerations as well as results
      of trials and their development. RECENT FINDINGS: Accumulation of evidence
      reinforces the concept of clinically significant disease. Latest histologic
      assessment studies specify the index lesion characteristics. Index lesion
      localization was accurately evaluated by both multiparametric MRI (mpMRI)
      targeted and transperineal mapping biopsy techniques against reference standard.
      mpMRI continues its development in accurate disease stratification. Development
      of new treatment modalities allows the clinician to investigate treatment of a
      lesion in various zonal anatomy locations. Consensus reports establish the
      intermediate risk population as the target for focal therapy, leaving very low
      risk disease to surveillance. Reviews of past clinical trials, including
      intermediate risk population, reveal encouraging oncologic follow-up. Ongoing
      trials will test focal therapy of index lesion with surveillance of insignificant
      secondary lesions. SUMMARY: Focal therapy should be investigated for intermediate
      risk population, leaving very low risk to surveillance. Detection and
      stratification techniques, namely mpMRI-targeted and transperineal biopsies, have
      an evolving role in lesion selection to confirm encouraging oncologic benefit for
      the patient.

PMID- 25844713
TI  - Characterization of Porphyrin-Co(III)-'Nitrene Radical' Species Relevant in
      Catalytic Nitrene Transfer Reactions.
AB  - To fully characterize the Co(III)-'nitrene radical' species that are proposed as
      intermediates in nitrene transfer reactions mediated by cobalt(II) porphyrins,
      different combinations of cobalt(II) complexes of porphyrins and nitrene transfer
      reagents were combined, and the generated species were studied using EPR, UV-vis,
      IR, VCD, UHR-ESI-MS, and XANES/XAFS measurements. Reactions of cobalt(II)
      porphyrins 1(P1) (P1 = meso-tetraphenylporphyrin (TPP)) and 1(P2) (P2 = 3,5
      Di(t)Bu-ChenPhyrin) with organic azides 2(Ns) (NsN3), 2(Ts) (TsN3), and 2(Troc)
      (TrocN3) led to the formation of mono-nitrene species 3(P1)(Ns), 3(P2)(Ts), and
      3(P2)(Troc), respectively, which are best described as [Co(III)(por)(NR"(*-))]
      nitrene radicals (imidyl radicals) resulting from single electron transfer from
      the cobalt(II) porphyrin to the 'nitrene' moiety (Ns: R" = -SO2-p-C6H5NO2; Ts: R"
      = -SO2C6H6; Troc: R" = -C(O)OCH2CCl3). Remarkably, the reaction of 1(P1) with N
      nosyl iminoiodane (PhI?NNs) 4(Ns) led to the formation of a bis-nitrene species
      5(P1)(Ns). This species is best described as a triple-radical complex [(por(*
      ))Co(III)(NR"(*-))2] containing three ligand-centered unpaired electrons: two
      nitrene radicals (NR"(*-)) and one oxidized porphyrin radical (por(*-)). Thus,
      the formation of the second nitrene radical involves another intramolecular one
      electron transfer to the "nitrene" moiety, but now from the porphyrin ring
      instead of the metal center. Interestingly, this bis-nitrene species is observed
      only on reacting 4(Ns) with 1(P1). Reaction of the more bulky 1(P2) with 4(Ns)
      results again in formation of mainly mono-nitrene species 3(P2)(Ns) according to
      EPR and ESI-MS spectroscopic studies. The mono- and bis-nitrene species were
      initially expected to be five- and six-coordinate species, respectively, but
      XANES data revealed that both mono- and bis-nitrene species are six-coordinate
      O(h) species. The nature of the sixth ligand bound to cobalt(III) in the mono
      nitrene case remains elusive, but some plausible candidates are NH3, NH2(-),
      NsNH(-), and OH(-); NsNH(-) being the most plausible. Conversion of mono-nitrene
      species 3(P1)(Ns) into bis-nitrene species 5(P1)(Ns) upon reaction with 4(Ns) was
      demonstrated. Solutions containing 3(P1)(Ns) and 5(P1)(Ns) proved to be still
      active in catalytic aziridination of styrene, consistent with their proposed key
      involvement in nitrene transfer reactions mediated by cobalt(II) porphyrins.

PMID- 25844716
TI  - Introduction to a series of articles that focus on methane.

PMID- 25844717
TI  - Mind wandering and selective attention to the external world.
AB  - From a cognitive neuroscience perspective, the study of attention has long
      centered on characterizing the basic systems we have in our brains for selecting
      what external sensory information to channel to our higher level, capacity
      limited processes in cortex. Less understood is how these attentional systems ebb
      and flow in their selectivity over seconds to minutes in the course of pursuing
      our daily activities. Toward illuminating this issue, here we review a recent
      series of studies we have conducted demonstrating that the degree to which our
      selective attention systems are engaged with the external environment is
      coordinated over these timescales such that they collectively engage and
      disengage together as a means of transiently modulating the depth of our
      cognitive investment in external sensory inputs. Although our studies have
      primarily focused on mind wandering in healthy, young participants, we suggest
      that people's ability to comprehensively attenuate their selective attention to
      the outside world plays a fundamental role in both normal human cognition and its
      clinical pathology.

PMID- 25844719
TI  - Sexist games=sexist gamers? A longitudinal study on the relationship between
      video game use and sexist attitudes.
AB  - From the oversexualized characters in fighting games, such as Dead or Alive or
      Ninja Gaiden, to the overuse of the damsel in distress trope in popular titles,
      such as the Super Mario series, the under- and misrepresentation of females in
      video games has been well documented in several content analyses. Cultivation
      theory suggests that long-term exposure to media content can affect perceptions
      of social realities in a way that they become more similar to the representations
      in the media and, in turn, impact one's beliefs and attitudes. Previous studies
      on video games and cultivation have often been cross-sectional or experimental,
      and the limited longitudinal work in this area has only considered time intervals
      of up to 1 month. Additionally, previous work in this area has focused on the
      effects of violent content and relied on self-selected or convenience samples
      composed mostly of adolescents or college students. Enlisting a 3 year
      longitudinal design, the present study assessed the relationship between video
      game use and sexist attitudes, using data from a representative sample of German
      players aged 14 and older (N=824). Controlling for age and education, it was
      found that sexist attitudes--measured with a brief scale assessing beliefs about
      gender roles in society--were not related to the amount of daily video game use
      or preference for specific genres for both female and male players. Implications
      for research on sexism in video games and cultivation effects of video games in
      general are discussed.

PMID- 25844718
TI  - Conserved epitopes on HIV-1, FIV and SIV p24 proteins are recognized by HIV-1
      infected subjects.
AB  - Cross-reactive peptides on HIV-1 and FIV p24 protein sequences were studied using
      peripheral blood mononuclear cells (PBMC) from untreated HIV-1-infected long-term
      survivors (LTS; >10 y of infection without antiretroviral therapy, ART), short
      term HIV-1 infected subjects not on ART, and ART-treated HIV-1 infected subjects.
      IFNgamma-ELISpot and CFSE-proliferation analyses were performed with PBMC using
      overlapping HIV-1 and FIV p24 peptides. Over half of the HIV-1 infected subjects
      tested (22/31 or 71%) responded to one or more FIV p24 peptide pools by either
      IFNgamma or T-cell proliferation analysis. PBMC and T cells from infected
      subjects in all 3 HIV(+) groups predominantly recognized one FIV p24 peptide pool
      (Fp14) by IFNgamma production and one additional FIV p24 peptide pool (Fp9) by T
      cell proliferation analysis. Furthermore, evaluation of overlapping SIV p24
      peptide sequences identified conserved epitope(s) on the Fp14/Hp15-counterpart of
      SIV, Sp14, but none on Fp9-counterpart of SIV, Sp9. The responses to these FIV
      peptide pools were highly reproducible and persisted throughout 2-4 y of
      monitoring. Intracellular staining analysis for cytotoxins and phenotyping for
      CD107a determined that peptide epitopes from Fp9 and Fp14 pools induced cytotoxic
      T lymphocyte-associated molecules including perforin, granzyme B, granzyme A,
      and/or expression of CD107a. Selected FIV and corresponding SIV epitopes
      recognized by HIV-1 infected patients indicate that these protein sequences are
      evolutionarily conserved on both SIV and HIV-1 (e.g., Hp15:Fp14:Sp14). These
      studies demonstrate that comparative immunogenicity analysis of HIV-1, FIV, and
      SIV can identify evolutionarily-conserved T cell-associated lentiviral epitopes,
      which could be used as a vaccine for prophylaxis or immunotherapy.

PMID- 25844721
TI  - Back to basics: an audit of measurement of infant growth at presentation to
      hospital.
AB  - OBJECTIVES: Infants who present or are admitted to hospital with illness or with
      inadequate growth and development are those most at risk of decreased nutritional
      status. However, not all infants who present or are admitted to hospital have
      their growth assessed. The aim of the present study was to identify how
      frequently anthropometric measurements were documented in charts of infants
      presenting and/or admitted to a tertiary paediatric hospital. METHODS: A
      systematic random sample of hospital charts of infants who had presented to the
      emergency department between 1 July 2011 and 30 June 2012 was audited
      retrospectively for the presence of appropriate documentation of measurement.
      RESULTS: In all, 465 charts were audited, representing 10% of infants who
      presented to the emergency department in the year. The frequency of
      anthropometric measures was: birthweight 103 (22%), presentation weight 275
      (59%), length 8 (2%), head circumference 15 (3%), percentiles 27 (6%) and body
      mass index score 1 (0%). Age of the infant was significantly associated with
      recording of birthweight. There were no significant relationships found between
      gender, socioeconomic status, gestational age, delivery type and recording of
      diagnosis and birthweight. CONCLUSIONS: Infant measurements were not recorded on
      many occasions. Assessment of growth as a marker of illness or nutritional
      deficit has been poorly assessed in this group. This is a missed opportunity to
      assess infant growth in this population, which has been found to be at risk of
      decreased nutritional status. Identification and treatment of growth deficits are
      a cost-effective method of optimising infant health worldwide.

PMID- 25844720
TI  - Inducible but not constitutive expression of PD-L1 in human melanoma cells is
      dependent on activation of NF-kappaB.
AB  - Monoclonal antibodies against immune checkpoint blockade have proven to be a
      major success in the treatment of melanoma. The programmed death receptor-1
      ligand-1 (PD-L1) expression on melanoma cells is believed to have an inhibitory
      effect on T cell responses and to be an important escape mechanism from immune
      attack. Previous studies have shown that PD-L1 can be expressed constitutively or
      can be induced by IFN-gamma secreted by infiltrating lymphocytes. In the present
      study we have investigated the mechanism underlying these two modes of PD-L1
      expression in melanoma cells including cells that had acquired resistance to the
      BRAF inhibitor vemurafenib. PD-L1 expression was examined by flow cytometry and
      immunoblotting. Specific inhibitors and siRNA knockdown approaches were used to
      examine the roles of the RAF/ MEK, PI3K, NF-kappaB, STAT3 and AP1/ c-Jun
      pathways. IFN-gamma inducible expression of PD-L1 was dependent on NF-kappaB as
      shown by inhibition with BMS-345541, an inhibitor of IkappaB and the BET protein
      inhibitor I-BET151, as well as by siRNA knockdown of NF-kappaB subunits. We were
      unable to implicate the BRAF/MEK pathway as major regulators in PD-L1 expression
      on vemurafenib resistant cells. Similarly the PI3K/AKT pathway and the
      transcription factors STAT3 and c-Jun had only minor roles in IFN-gamma induced
      expression of PD-L1. The mechanism underlying constitutive expression remains
      unresolved. We suggest these results have significance in selection of treatments
      that can be used in combination with monoclonal antibodies against PD1, to
      enhance their effectiveness and to reduce inhibitory effects melanoma cells have
      against cytotoxic T cell activity. 

PMID- 25844723
TI  - Pattern of paediatric dermatoses at dermatology clinics in Ile-Ife and Ilesha,
      Nigeria.
AB  - BACKGROUND: In developing countries, skin diseases are one of the most common
      causes of morbidity. AIM: A prospective descriptive study was conducted to
      determine the pattern of skin diseases in childhood and adolescents presenting to
      the outpatient dermatology clinics of Obafemi Awolowo University Teaching
      Hospitals Complex at Ile-Ife and Ilesha, Osun State. METHODS: Patients aged 2
      weeks to 19 years attending the clinics between October 2009 and September 2012
      were included. RESULTS: A total of 491 dermatoses were recorded in 441 patients.
      There were 244 (49.6%) males. Dermatophyte infections (17.1%), papular urticaria
      (6.7%), atopic dermatitis (6.3%), vitiligo (5.3%), acne (4.7%) and viral warts
      (3.7%) were the most frequent dermatoses. Skin infections and infestations,
      mostly dermatophyte infections and viral warts, accounted for 57.6% of the skin
      conditions. Of the non-infectious diseases, papular urticaria and atopic
      dermatitis were the most common. Dermatophyte infections were the most prevalent
      in children (25.8%), and acne vulgaris in adolescents (11.8%). CONCLUSION: Skin
      infections and infestations, mostly dermatophyte infections, were the most
      prevalent in children, and acne vulgaris in adolescents.

PMID- 25844724
TI  - Development of new assays for Epstein-Barr and porcine epidemic diarrhea viruses.

PMID- 25844725
TI  - Cognition and Quality-of-Life Outcomes in the Targeted Temperature Management
      Trial for Cardiac Arrest.

PMID- 25844722
TI  - Signs analysis and clinical assessment: phase-contrast computed tomography of
      human breast tumours.
AB  - PURPOSE: To analyse the diagnostic signs present in slices of human breast tumour
      specimens using synchrotron radiation phase-contrast imaging computed tomography
      (PCI-CT) for the first time and assess the feasibility of this technique for
      clinical applications. MATERIALS AND METHODS: The ethics committee of our
      university and relevant clinical hospital approved this prospective study, and
      written informed consent was obtained from all patients. PCI-CT of human breast
      tumour specimens with synchrotron radiation was performed at the Shanghai
      Synchrotron Radiation Facility (SSRF). A total of 14 specimens of early-stage
      carcinomas and 8 specimens of adenomas were enrolled. Based on raw data
      reconstruction, the diagnostic signs present in the slices were analysed and
      correlated with histopathology. We proposed a criterion for clinical diagnosis
      according to the evaluated signs and the Breast Imaging Reporting and Data System
      (BI-RADS) for reference. The criterion was then assessed by clinicians in a
      double-blind method. Finally, descriptive statistics were evaluated, depending on
      the assessment results. RESULTS: The 14 carcinoma specimens and 8 adenoma
      specimens were diagnosed as malignant and benign tumours, respectively. The total
      coincidence rate was 100%. CONCLUSION: Our study results demonstrate that the X
      ray diagnostic signs observed in the specimen slices and the criterion used for
      clinical diagnosis were accurate and reliable. The criterion based on signs
      analysis can be used to differentiate early-stage benign or malignant tumours. As
      a promising imaging method, PCI-CT can serve as a possible and feasible
      supplement to BI-RADS in the future.

PMID- 25844726
TI  - What is the right number of clinic appointments?: Visit frequency and the
      accountable care organization.

PMID- 25844727
TI  - The Future of the National Children's Study.

PMID- 25844728
TI  - Understanding how institutional culture affects attending physicians' and
      trainees' resuscitation discussions.

PMID- 25844729
TI  - The Stabilizing Role of the Intramolecular C-H...O Hydrogen Bond in Cyclic Amides
      Derived From alpha-Methylbenzylamine.
AB  - A series of five-, six-, seven-, and eight-membered lactams containing the chiral
      auxiliary alpha-methylbenzylamine were structurally analyzed and further studied
      by DFT calculations with the purpose to examine with detail the previously
      detected intramolecular C-H...O hydrogen-bonding interaction formed between the
      hydrogen atom of the alpha-methylbenzylamine and the carbonyl group of the cyclic
      amide. The main objective was to establish whether its presence does have a
      tangible relevance in their spatial arrangement in solution and in the solid
      state or is a simple and not stabilizing interaction. 

PMID- 25844731
TI  - Enhanced Electroresponsive Performance of Double-Shell SiO2/TiO2 Hollow
      Nanoparticles.
AB  - The double-shell SiO2/TiO2 hollow nanoparticles (DS HNPs) are successfully
      fabricated and adopted as dispersing materials for electrorheological (ER) fluids
      to investigate an influence of shell structure on ER properties. The DS HNPs
      based ER fluid exhibits outstanding ER performance which is 4.1-fold higher
      compared to that of single shell SiO2/TiO2 hollow nanoparticles (SS HNPs)-based
      ER fluid. The significantly improved ER property of DS HNPs-based ER fluid is
      ascribed to the enhanced interfacial polarization. In addition, the ER activities
      of DS HNPs-based ER fluids are examined depending on the particle diameter. The
      yield stress of DS HNPs-based ER fluids increases up to 302.4 kPa under an
      electric field of 3 kV mm(-1) by reducing the particle size, which is remarkable
      performance enough to promise sufficient probability for practical and industrial
      applications. The enhanced ER performance of the smaller DS HNPs is attributed to
      the increased surface area of large pores (30-35 nm) within the shells, resulting
      in a large achievable polarizability determined by dielectric constants.
      Furthermore, the antisedimentation property is analyzed in order to offer an
      additional insight into the effect of particle size on the ER fluids. 

PMID- 25844730
TI  - Leisure time physical activity and mortality: a detailed pooled analysis of the
      dose-response relationship.
AB  - IMPORTANCE: The 2008 Physical Activity Guidelines for Americans recommended a
      minimum of 75 vigorous-intensity or 150 moderate-intensity minutes per week (7.5
      metabolic-equivalent hours per week) of aerobic activity for substantial health
      benefit and suggested additional benefits by doing more than double this amount.
      However, the upper limit of longevity benefit or possible harm with more physical
      activity is unclear. OBJECTIVE: To quantify the dose-response association between
      leisure time physical activity and mortality and define the upper limit of
      benefit or harm associated with increased levels of physical activity. DESIGN,
      SETTING, AND PARTICIPANTS: We pooled data from 6 studies in the National Cancer
      Institute Cohort Consortium (baseline 1992-2003). Population-based prospective
      cohorts in the United States and Europe with self-reported physical activity were
      analyzed in 2014. A total of 661,137 men and women (median age, 62 years; range,
      21-98 years) and 116,686 deaths were included. We used Cox proportional hazards
      regression with cohort stratification to generate multivariable-adjusted hazard
      ratios (HRs) and 95% CIs. Median follow-up time was 14.2 years. EXPOSURES:
      Leisure time moderate- to vigorous-intensity physical activity. MAIN OUTCOMES AND
      MEASURES: The upper limit of mortality benefit from high levels of leisure time
      physical activity. RESULTS: Compared with individuals reporting no leisure time
      physical activity, we observed a 20% lower mortality risk among those performing
      less than the recommended minimum of 7.5 metabolic-equivalent hours per week (HR,
      0.80 [95% CI, 0.78-0.82]), a 31% lower risk at 1 to 2 times the recommended
      minimum (HR, 0.69 [95% CI, 0.67-0.70]), and a 37% lower risk at 2 to 3 times the
      minimum (HR, 0.63 [95% CI, 0.62-0.65]). An upper threshold for mortality benefit
      occurred at 3 to 5 times the physical activity recommendation (HR, 0.61 [95% CI,
      0.59-0.62]); however, compared with the recommended minimum, the additional
      benefit was modest (31% vs 39%). There was no evidence of harm at 10 or more
      times the recommended minimum (HR, 0.69 [95% CI, 0.59-0.78]). A similar dose
      response relationship was observed for mortality due to cardiovascular disease
      and to cancer. CONCLUSIONS AND RELEVANCE: Meeting the 2008 Physical Activity
      Guidelines for Americans minimum by either moderate- or vigorous-intensity
      activities was associated with nearly the maximum longevity benefit. We observed
      a benefit threshold at approximately 3 to 5 times the recommended leisure time
      physical activity minimum and no excess risk at 10 or more times the minimum. In
      regard to mortality, health care professionals should encourage inactive adults
      to perform leisure time physical activity and do not need to discourage adults
      who already participate in high-activity levels.

PMID- 25844734
TI  - Adjunctive diagnostic procedures for percutaneous coronary intervention.

PMID- 25844735
TI  - Improving physician well-being.

PMID- 25844736
TI  - Improving physician well-being.

PMID- 25844737
TI  - Improving physician well-being--reply.

PMID- 25844738
TI  - Sex-specific chest pain characteristics.

PMID- 25844739
TI  - Effect of wine consumption on mortality.

PMID- 25844740
TI  - Sex-specific chest pain characteristics--reply.

PMID- 25844741
TI  - Evaluating clinical management decisions by recent graduates in the era of high
      value, cost-conscious care.

PMID- 25844742
TI  - Effect of wine consumption on mortality--reply.

PMID- 25844743
TI  - Evaluating clinical management decisions by recent graduates in the era of high
      value, cost-conscious care--reply.

PMID- 25844744
TI  - For deep vein thrombosis, follow the randomized trials.

PMID- 25844745
TI  - For deep vein thrombosis, follow the randomized trials--reply.

PMID- 25844746
TI  - Metrics for evaluating the quality of handovers.

PMID- 25844747
TI  - What ecologic analyses cannot tell us about medical marijuana legalization and
      opioid pain medication mortality.

PMID- 25844748
TI  - Metrics for evaluating the quality of handovers--reply.

PMID- 25844749
TI  - What ecologic analyses cannot tell us about medical marijuana legalization and
      opioid pain medication mortality--reply.

PMID- 25844750
TI  - Concern about the use of venlafaxine to treat vasomotor symptoms.

PMID- 25844751
TI  - beta-Blockers in diabetic patients with heart failure.

PMID- 25844752
TI  - beta-Blockers in diabetic patients with heart failure--reply.

PMID- 25844753
TI  - Concern about the use of venlafaxine to treat vasomotor symptoms--reply.

PMID- 25844754
TI  - Error in methods.

PMID- 25844755
TI  - Error in figures.

PMID- 25844756
TI  - Lurasidone in the treatment of bipolar depression with mixed (subsyndromal
      hypomanic) features: post hoc analysis of a randomized placebo-controlled trial.
AB  - OBJECTIVE: Mixed (subsyndromal hypomanic) features are prevalent in patients with
      bipolar depression and are associated with more severe and complex illness,
      including increased risk for suicide attempts, higher switch to mania during
      antidepressant therapy, and a higher rate of recurrence. The aim of this post hoc
      analysis was to evaluate the efficacy and safety of lurasidone in the treatment
      of patients with bipolar depression presenting with mixed features. METHOD:
      Patients with a DSM-IV-TR diagnosis of major depressive episode associated with
      bipolar I disorder, with or without rapid cycling, and with a Montgomery-Asberg
      Depression Rating Scale (MADRS) score >= 20 and a Young Mania Rating Scale (YMRS)
      score <= 12 were randomly assigned to 6 weeks of double-blind, once-daily
      treatment with lurasidone 20-60 mg, lurasidone 80-120 mg, or placebo. The
      presence of mixed features was defined as a YMRS score >= 4 at study baseline.
      Efficacy analyses included change in MADRS total score from baseline to week 6
      (the primary outcome in the original study, conducted between April 2009 and
      February 2012). RESULTS: At baseline, mixed features were present in 56% of
      patients (lurasidone, n = 182/323; placebo, n = 90/162). Treatment with
      lurasidone (vs placebo) was associated with significantly greater reductions in
      MADRS scores in the mixed features group (-15.7 vs -10.9; P = .001; week 6; mixed
      model for repeated measures [MMRM]; effect size, 0.48) and in the group without
      mixed features (-15.2 vs -10.8; P = .002; week 6; MMRM; effect size, 0.48). Rates
      of protocol-defined treatment-emergent hypomania or mania were similar for
      patients with mixed features (lurasidone, 2.2%; placebo, 3.2%) and without mixed
      features (lurasidone, 3.4%; placebo, 0.0%). CONCLUSIONS: Lurasidone was found in
      this post hoc analysis to be efficacious in the treatment of patients with
      bipolar depression who present with mixed features (assessed cross-sectionally at
      study baseline). No increased risk of treatment-emergent mania was observed in
      either group. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00868699.

PMID- 25844757
TI  - Aluminum plasmonic multicolor meta-hologram.
AB  - We report a phase-modulated multicolor meta-hologram (MCMH) that is polarization
      dependent and capable of producing images in three primary colors. The MCMH
      structure is made of aluminum nanorods that are arranged in a two-dimensional
      array of pixels with surface plasmon resonances in red, green, and blue. The
      aluminum nanorod array is patterned on a 30 nm thick SiO2 spacer layer sputtered
      on top of a 130 nm thick aluminum mirror. With proper design of the structure, we
      obtain resonances of narrow bandwidths to allow for implementation of the
      multicolor scheme. Taking into account of the wavelength dependence of the
      diffraction angle, we can project images to specific locations with predetermined
      size and order. With tuning of aluminum nanorod size, we demonstrate that the
      image color can be continuously varied across the visible spectrum. 

PMID- 25844758
TI  - Kidney-type glutaminase (GLS1) is a biomarker for pathologic diagnosis and
      prognosis of hepatocellular carcinoma.
AB  - The lack of sensitive and specific biomarkers hinders pathological diagnosis and
      prognosis for hepatocellular carcinoma (HCC). Since glutaminolysis plays a
      crucial role in carcinogenesis and progression, we sought to determine if the
      expression of kidney-type and liver-type glutaminases (GLS1 and GLS2) were
      informative for pathological diagnosis and prognosis of HCC. We compared the
      expression of GLS1 and GLS2 in a large set of clinical samples including HCC,
      normal liver, and other liver diseases. We found that GLS1 was highly expressed
      in HCC; whereas, expression of GLS2 was mainly confined to non-tumor hepatocytes.
      The sensitivity and specificity of GLS1 for HCC were 96.51% and 75.21%,
      respectively. A metabolic switch from GLS2 to GLS1 was observed in a series of
      tissues representing progressive pathologic states mimicking HCC oncogenic
      transformation, including normal liver, fibrotic liver, dysplasia nodule, and
      HCC. We found that high expression of GLS1 and low expression of GLS2 in HCC
      correlated with survival time of HCC patients. Expression of GLS1 and GLS2 were
      independent indexes for survival time; however, prognosis was predominantly
      determined by the level of GLS1 expression. These findings indicate that GLS1
      expression is a sensitive and specific biomarker for pathological diagnosis and
      prognosis of HCC.

PMID- 25844759
TI  - History of Mechanical Ventilation. From Vesalius to Ventilator-induced Lung
      Injury.
AB  - Mechanical ventilation is a life-saving therapy that catalyzed the development of
      modern intensive care units. The origins of modern mechanical ventilation can be
      traced back about five centuries to the seminal work of Andreas Vesalius. This
      article is a short history of mechanical ventilation, tracing its origins over
      the centuries to the present day. One of the great advances in ventilatory
      support over the past few decades has been the development of lung-protective
      ventilatory strategies, based on our understanding of the iatrogenic consequences
      of mechanical ventilation such as ventilator-induced lung injury. These
      strategies have markedly improved clinical outcomes in patients with respiratory
      failure. 

PMID- 25844761
TI  - Surface pressure and microstructure of carbon nanotubes at an air-water
      interface.
AB  - This article reports the surface pressure and microstructure of two different
      types of carbon nanotubes (CNTs) at an air-water interface; namely, as-produced
      CNTs (nf-CNTs) and CNTs functionalized with carboxyl groups (f-CNTs). Both types
      of CNTs formed 3D aggregates upon compression using a Langmuir-Pockels trough.
      However, f-CNTs showed a lower degree of aggregation compared with that of nf
      CNTs. This is attributed to the deprotonation of the carboxyl groups within the
      water subphase, leading to additional electrostatic repulsion between f-CNTs. For
      the same initial amount of CNTs spread onto the interface, the actual coverage of
      f-CNTs was higher than that of nf-CNTs at a given trough area. At high
      compression, f-CNTs formed aligned CNT domains at the interface. These 2D domains
      resembled 3D liquid-crystalline structures formed by excluded volume
      interactions. The denser packing and orientational ordering of f-CNTs also
      contributed to a compressional modulus higher than that of nf-CNTs, as calculated
      from the surface pressure isotherms. A Volmer equation of state was applied to
      model the measured surface pressure containing both thermodynamic and mechanical
      contributions. The Volmer model, however, did not consider the loss of CNTs from
      the interface due to 3D aggregation and consequently overestimated the surface
      pressure at high compression. The actual coverage of CNT during compression was
      back calculated from the model and was in agreement with the value obtained
      independently from optical micrographs. The findings of this work may have a
      broader impact on understanding the assembly and collective behavior of rod-like
      particles with a high aspect ratio at an air-water interface. 

PMID- 25844760
TI  - Tetrahydroindazoles as Interleukin-2 Inducible T-Cell Kinase Inhibitors. Part II.
      Second-Generation Analogues with Enhanced Potency, Selectivity, and
      Pharmacodynamic Modulation in Vivo.
AB  - The medicinal chemistry community has directed considerable efforts toward the
      discovery of selective inhibitors of interleukin-2 inducible T-cell kinase (ITK),
      given its role in T-cell signaling downstream of the T-cell receptor (TCR) and
      the implications of this target for inflammatory disorders such as asthma. We
      have previously disclosed a structure- and property-guided lead optimization
      effort which resulted in the discovery of a new series of tetrahydroindazole
      containing selective ITK inhibitors. Herein we disclose further optimization of
      this series that resulted in further potency improvements, reduced off-target
      receptor binding liabilities, and reduced cytotoxicity. Specifically, we have
      identified a correlation between the basicity of solubilizing elements in the ITK
      inhibitors and off-target antiproliferative effects, which was exploited to
      reduce cytotoxicity while maintaining kinase selectivity. Optimized analogues
      were shown to reduce IL-2 and IL-13 production in vivo following oral or
      intraperitoneal dosing in mice. 

PMID- 25844764
TI  - Here comes the sun--is vitamin D a cure for all that ails us?

PMID- 25844763
TI  - Commentary: Launch of a quality improvement network for evidence-based management
      of uncommon pediatric endocrine disorders: Turner syndrome as a prototype.
AB  - BACKGROUND: Traditional, hypothesis-oriented research approaches have thus far
      failed to generate sufficient evidence to achieve consensus about the management
      of children with many endocrine disorders, partly because of the rarity of these
      disorders and because of regulatory burdens unique to research in children.
      OBJECTIVE: The Pediatric Endocrine Society is launching a quality improvement
      network in spring 2015 for the management of pediatric endocrine disorders that
      are relatively uncommon in any single practice and/or for which there is no
      consensus on management. DESIGN: The first of the quality improvement programs to
      be implemented seeks to improve the care of 11- to 17-year-old girls with Turner
      syndrome who require initiation of estrogen replacement therapy by providing a
      standardized clinical assessment and management plan (SCAMP) for transdermal
      estradiol treatment to induce pubertal development. The SCAMP algorithm
      represents a starting point within current best practice that is meant to undergo
      refinement through an iterative process of analysis of deidentified data
      collected in the course of clinical care by a network of pediatric
      endocrinologists. CONCLUSION: It is anticipated that this program will not only
      improve care, but will also result in actionable data that will generate new
      research hypotheses and changes in management of pediatric endocrine disorders.

PMID- 25844765
TI  - Making it real--the environmental burden of disease. What does it take to make
      people pay attention to the environment and health?

PMID- 25844767
TI  - Erratum.

PMID- 25844766
TI  - Corrigenda.

PMID- 25844770
TI  - Letter to the editor: Per-operative hemodynamic instability in normotensive
      patients with incidentally discovered pheochromocytomas.

PMID- 25844771
TI  - Response to the letter by Gaujoux S., et al.

PMID- 25844772
TI  - Letter to the editor: Treatment of Paget's disease in patients with renal
      impairment.

PMID- 25844773
TI  - Response to the letter by Asik M., et al.

PMID- 25844774
TI  - Methodologically sound: Evaluating the psychometric approach to the assessment of
      human life history [reply to Copping, Campbell, and Muncer, 2014].
AB  - Copping, Campbell, and Muncer (2014) have recently published an article critical
      of the psychometric approach to the assessment of life history (LH) strategy.
      Their purported goal was testing for the convergent validation and examining the
      psychometric structure of the High-K Strategy Scale (HKSS). As much of the
      literature on the psychometrics of human LH during the past decade or so has
      emanated from our research laboratory and those of close collaborators, we have
      prepared this detailed response. Our response is organized into four main
      sections: (1) A review of psychometric methods for the assessment of human LH
      strategy, expounding upon the essence of our approach; (2) our
      theoretical/conceptual concerns regarding the critique, addressing the broader
      issues raised by the critique regarding the latent and hierarchical structure of
      LH strategy; (3) our statistical/methodological concerns regarding the critique,
      examining the validity and persuasiveness of the empirical case made specifically
      against the HKSS; and (4) our recommendations for future research that we think
      might be helpful in closing the gap between the psychometric and biometric
      approaches to measurement in this area. Clearly stating our theoretical
      positions, describing our existing body of work, and acknowledging their
      limitations should assist future researchers in planning and implementing more
      informed and prudent empirical research that will synthesize the psychometric
      approach to the assessment of LH strategy with complementary methods.

PMID- 25844775
TI  - Modeling the relationship between family home environment factors and parental
      health.
AB  - INTRODUCTION: Understanding parental health is an important part of understanding
      family health. Previous research suggests that family meals, familial
      relationship satisfaction, and family physical activity may separately be related
      to physical health. METHOD: The current study aims to combine these variables
      into a structural equation model to determine the collective relationship they
      have with adult health within a sample of parents (n = 1,435). Most parents were
      married, White, and highly educated. RESULTS: The relationship between family
      meals and parental health was significant (beta = -.07, t = -2.29, p < .05), with
      the full model having adequate fit and accounting for some of the overall
      variance in parental health. Familial relationship satisfaction and family
      physical activity were not found to be associated with parental health.
      Exploratory findings of the sample stratified by biological sex are described.
      DISCUSSION: Findings from the current study were consistent with a systemic
      perspective in that parents may have health benefits when they participate in
      family-level behavior (e.g., family meals). Additional areas for research and
      limitations to the current study are also discussed.

PMID- 25844776
TI  - Please break the silence: Parents' views on communication between pediatric
      primary care and mental health providers.
AB  - INTRODUCTION: The purpose of this study was to gain a better understanding of
      parents' preferences regarding the sharing of information between their
      children's primary care and mental health providers. METHOD: Fifty-five parents
      with a child who was actively engaged in mental health treatment completed an
      anonymous survey while accompanying their child to either a primary care or
      mental health clinic appointment. This brief measure elicited parents'
      experiences with and preferences for treatment coordination across their
      children's primary care and mental health providers, with a focus on
      communication practices. RESULTS: Parents consistently described communication
      among their children's primary care and mental health providers as important, yet
      frequently reported that such communication was not currently taking place.
      Further, parents reported that they were often called upon to act as
      "communication bridges" between professionals caring for their children.
      DISCUSSION: Implications for the collaborative pediatric and mental health care
      of children as well as recommendations for improving communication between mental
      health and pediatric providers are discussed.

PMID- 25844777
TI  - Spontaneous activity in the precuneus predicts individual differences in verbal
      fluency in cognitively normal elderly.
AB  - OBJECTIVE: The precuneus is 1 of the major cortical hubs and plays an important
      role in normal aging and verbal fluency processing. The main aim of present study
      was to investigate how intrinsic brain activity in the precuneus at rest predicts
      individual differences in verbal fluency ability among elderly adults. METHOD:
      Regional amplitude of low-frequency fluctuations (ALFF) analysis and a
      correlation-based functional connectivity (FC) approach were used to analyze data
      acquired from 101 cognitively normal elderly. RESULTS: ALFF in the precuneus
      declined with normal aging and was significantly correlated with individual
      differences in performance on the verbal fluency test (VFT). Specifically, ALFF
      in the precuneus was reduced in elderly with high fluency (HF) ability compared
      with those with low fluency (LF) ability. In addition, the HF individuals
      displayed increased functional connectivity of the precuneus with the lateral
      temporal area and prefrontal lobe, including the inferior frontal, medial
      frontal, superior temporal, middle temporal, and superior frontal gyri.
      CONCLUSION: Spontaneous activity in the precuneus could predict individual
      differences in verbal fluency processing. Our results suggest that spontaneous
      activity in the precuneus is an indicator of aging-related changes in semantic
      verbal fluency processing, or even a potential biomarker for the early detection
      of semantic verbal fluency deterioration.

PMID- 25844778
TI  - First refusal.

PMID- 25844779
TI  - What's eating you? Cutaneous larva migrans.
AB  - This article provides a focused update and clinical review on cutaneous larva
      migrans (CLM), including atypical clinical presentations and newer management
      recommendations. The results and recommendations are subject to modification
      based on future studies. 

PMID- 25844780
TI  - Update on pediatric psoriasis.
AB  - Pediatric psoriasis accounts for approximately one-third of all cases of
      psoriasis. Although pediatric psoriasis was always understood to be a chronic
      inflammatory dermatosis, recent data suggest that pediatric psoriasis, similar to
      its adult equivalent, is part of a generalized inflammatory diathesis associated
      with metabolic syndrome, including obesity/overweight status,
      hypertriglyceridemia, high blood pressure, and insulin resistance. Given the
      recent proliferation of data demonstrating the generalized inflammatory nature of
      psoriasis, a new emphasis on adopting a healthier lifestyle and weight control as
      well as systemic therapies has emerged in the literature. This article briefly
      reviews selected studies published in the last 2 years that are pertinent to
      pediatric psoriasis. 

PMID- 25844781
TI  - New systemic therapies for psoriasis.
AB  - Over the last decade, expanded understanding of psoriasis pathogenesis has led to
      the development of new systemic agents such as biological drugs that have
      revolutionized the treatment of psoriasis. Small molecule inhibitors also have
      been studied and offer patients options for oral administration. This article
      reviews recently approved and in-the-pipeline biologics (IL-17 inhibitors and IL
      23 blockers) as well as small molecule inhibitors (phosphodiesterase 4 [PDE4] and
      Janus kinase [Jak] inhibitors). 

PMID- 25844782
TI  - Disease burden and quality of life in psoriasis patients with and without
      comorbid psoriatic arthritis: results from National Psoriasis Foundation panel
      surveys.
AB  - The comorbidity profile and overall disease impact are not well understood in
      psoriasis with and without comorbid psoriatic arthritis (PsA). The objective of
      this study was to compare disease characteristics, comorbidities, and psoriasis
      related quality of life (QOL) in patients with moderate to severe psoriasis with
      and without comorbid PsA using results from National Psoriasis Foundation (NPF)
      surveys. The study included 3395 and 2072 patients with psoriasis alone and
      psoriasis with PsA, respectively. The results showed the burden of psoriasis
      either independently or with comorbid PsA. As severity of psoriasis increased,
      patient health and QOL were found to decline. 

PMID- 25844783
TI  - Onchocerciasis.

PMID- 25844784
TI  - What is your diagnosis? Extramammary Paget disease.

PMID- 25844785
TI  - Novel psoriasis therapies and patient outcomes, part 1: topical medications.
AB  - In recent years, advances in our understanding of inflammatory mediators and the
      underlying pathogenesis of psoriasis and psoriatic arthritis have shed light on
      potential therapeutic targets, which has led to the development of several new
      promising treatments. In this article, key clinical trials, mechanisms of action,
      patient outcomes, and relevant safety information for these novel topical
      medications will be evaluated. This article is the first in a 3-part series on
      treatments presently in the pipeline for the management of psoriasis and
      psoriatic arthritis including topical agents, biologic treatments, and systemic
      therapies in phase 2 and phase 3 clinical trials. With novel approaches to the
      disease process, these therapies may afford more targeted individualized
      treatment regimens and offer hope to patients with psoriasis and psoriatic
      arthritis who have reported a suboptimal therapeutic response to conventional
      therapies. 

PMID- 25844786
TI  - Subcutaneous sarcoidosis on ultrasonography.

PMID- 25844787
TI  - Bluish red verrucous lesions on the leg.

PMID- 25844788
TI  - Inability to grow long hair: a presentation of trichorrhexis nodosa.

PMID- 25844789
TI  - Plasmapheresis in refractory pemphigus vulgaris: revisiting an old treatment
      modality used in synchrony with pulse cyclophosphamide.

PMID- 25844790
TI  - A case of Morfan syndrome.

PMID- 25844791
TI  - Trigeminal trophic syndrome with histopathologic correlation.
AB  - We present the case of a 49-year-old woman with trigeminal trophic syndrome
      (TTS), also known as trophic trigeminal neuralgia, trigeminal neurotrophic
      ulceration, and/or trigeminal neuropathy with nasal ulceration. Our case
      represents an uncommon report of intractable itching and chronic pain associated
      with TTS. Emphasis was placed on skin biopsy histology, which revealed no
      neuronal innervation of the affected scalp despite reports of intractable itching
      and chronic pain. Trigeminal trophic syndrome of the V1 branch of the trigeminal
      nerve secondary to herpes zoster (HZ) with correlated histology is described.
      This article provides a discussion of TTS and correlated histology as well as a
      brief discussion of intractable itching and postherpetic neuralgia. 

PMID- 25844792
TI  - Glatiramer acetate-induced lobular panniculitis and skin necrosis.
AB  - Glatiramer acetate (GA) is a drug that commonly is used for the treatment of
      relapsing-remitting multiple sclerosis (RRMS). Although it typically is known as
      a safe and effective therapy, a number of adverse effects associated with GA have
      been reported in the literature. Local injection-site reactions (LISRs) and mild
      systemic symptoms are among the most commonly described adverse effects. A review
      of the literature revealed limited reports of panniculitis as an adverse effect
      of GA injection and even fewer describing associated skin necrosis. We report a
      case of GA-induced panniculitis and skin necrosis and discuss the occurrence of
      panniculitis, necrosis, and lipoatrophy following GA injections. 

PMID- 25844794
TI  - Fellowships after dermatology residency: the traditional and beyond.
AB  - Postresidency fellowship training options exist for graduating dermatology
      residents. Formal subspecialty fellowship programs are offered in
      dermatopathology, pediatric dermatology, micrographic surgery and dermatologic
      oncology (procedural dermatology), and cosmetic dermatologic surgery. There also
      are a number of fellowships offered at certain institutions for those interested
      in more specific subspecialties or academia. This guide serves to assist
      dermatology residents in learning more about fellowship opportunities. 

PMID- 25844793
TI  - Identification of cutaneous warts: cryotherapy-induced acetowhitelike epithelium.

PMID- 25844795
TI  - Telangiectases on the cheeks and nose.

PMID- 25844796
TI  - Friable nodule on the back.

PMID- 25844797
TI  - Abscisic Acid Acts as a Blocker of the Bitter Taste G Protein-Coupled Receptor
      T2R4.
AB  - Bitter taste receptors (T2Rs) belong to the G protein-coupled receptor
      superfamily. In humans, 25 T2Rs mediate bitter taste sensation. In addition to
      the oral cavity, T2Rs are expressed in many extraoral tissues, including the
      central nervous system, respiratory system, and reproductive system. To
      understand the mechanistic roles of the T2Rs in oral and extraoral tissues, novel
      blockers or antagonists are urgently needed. Recently, we elucidated the binding
      pocket of T2R4 for its agonist quinine, and an antagonist and inhibitory
      neurotransmitter, gamma-aminobutyric acid. This structure-function information
      about T2R4 led us to screen the plant hormone abscisic acid (ABA), its precursor
      (xanthoxin), and catabolite phaseic acid for their ability to bind and activate
      or inhibit T2R4. Molecular docking studies followed by functional assays
      involving calcium imaging confirmed that ABA is an antagonist with an IC50 value
      of 34.4 +/- 1.1 MUM. However, ABA precursor xanthoxin acts as an agonist on T2R4.
      Interestingly, molecular model-guided site-directed mutagenesis suggests that the
      T2R4 residues involved in quinine binding are also predominantly involved in
      binding to the novel antagonist, ABA. The antagonist ability of ABA was tested
      using another T2R4 agonist, yohimbine. Our results suggest that ABA does not
      inhibit yohimbine-induced T2R4 activity. The discovery of natural bitter blockers
      has immense nutraceutical and physiological significance and will help in
      dissecting the T2R molecular pathways in various tissues. 

PMID- 25844798
TI  - Electrochemical DNA Biosensor Based on a Tetrahedral Nanostructure Probe for the
      Detection of Avian Influenza A (H7N9) Virus.
AB  - A DNA tetrahedral nanostructure-based electrochemical biosensor was developed to
      detect avian influenza A (H7N9) virus through recognizing a fragment of the
      hemagglutinin gene sequence. The DNA tetrahedral probe was immobilized onto a
      gold electrode surface based on self-assembly between three thiolated nucleotide
      sequences and a longer nucleotide sequence containing complementary DNA to
      hybridize with the target single-stranded (ss)DNA. The captured target sequence
      was hybridized with a biotinylated-ssDNA oligonucleotide as a detection probe,
      and then avidin-horseradish peroxidase was introduced to produce an amperometric
      signal through the interaction with 3,3',5,5'-tetramethylbenzidine substrate. The
      target ssDNA was obtained by asymmetric polymerase chain reaction (PCR) of the
      cDNA template, reversely transcribed from the viral lysate of influenza A (H7N9)
      virus in throat swabs. The results showed that this electrochemical biosensor
      could specifically recognize the target DNA fragment of influenza A (H7N9) virus
      from other types of influenza viruses, such as influenza A (H1N1) and (H3N2)
      viruses, and even from single-base mismatches of oligonucleotides. Its detection
      limit could reach a magnitude of 100 fM for target nucleotide sequences.
      Moreover, the cycle number of the asymmetric PCR could be reduced below three
      with the electrochemical biosensor still distinguishing the target sequence from
      the negative control. To the best of our knowledge, this is the first report of
      the detection of target DNA from clinical samples using a tetrahedral DNA probe
      functionalized electrochemical biosensor. It displays that the DNA tetrahedra has
      a great potential application as a probe of the electrochemical biosensor to
      detect avian influenza A (H7N9) virus and other pathogens at the gene level,
      which will potentially aid the prevention and control of the disease caused by
      such pathogens. 

PMID- 25844799
TI  - Correction to multifunctional rare-earth vanadate nanoparticles: luminescent
      labels, oxidant sensors, and MRI contrast agents.

PMID- 25844800
TI  - Pillar cuvettes: capillary-filled, microliter quartz cuvettes with microscale
      path lengths for optical spectroscopy.
AB  - The goal of most analytical techniques is to reduce the lower limit of detection;
      however, it is sometimes necessary to do the opposite. High sample concentrations
      or samples with high molar absorptivity (e.g., dyes and metal complexes) often
      require multiple dilution steps or laborious sample preparation prior to
      spectroscopic analysis. Here, we demonstrate dilution-free, one-step UV-vis
      spectroscopic analysis of high concentrations of platinum(IV) hexachloride in a
      micropillar array, that is, "pillar cuvette". The cuvette is spontaneously filled
      by wicking of the liquid sample into the micropillar array. The pillar height
      (thus, the film thickness) defines the optical path length, which was reduced to
      between 10 and 20 MUm in this study (3 orders of magnitude smaller than in a
      typical cuvette). Only one small droplet (~2 MUL) of sample is required, and the
      dispensed volume need not be precise or even known to the analyst for accurate
      spectroscopy measurements. For opaque pillars, we show that absorbance is
      linearly related to platinum concentration (the Beer-Lambert Law). For fully
      transparent or semitransparent pillars, the measured absorbance was successfully
      corrected for the fractional surface coverage of the pillars and the
      transmittance of the pillars and reference. Thus, both opaque and transparent
      pillars can be applied to absorbance spectroscopy of high absorptivity,
      microliter samples. It is also shown here that the pillar array has a useful
      secondary function as an integrated (in-cuvette) filter for particulates. For
      pillar cuvette measurements of platinum solutions spiked with 6 MUm diameter
      polystyrene spheres, filtered and unfiltered samples gave identical spectra. 

PMID- 25844801
TI  - Dilemma of sewage sludge treatment and disposal in China.

PMID- 25844802
TI  - "Clickable" Polymeric Nanofibers through Hydrophilic-Hydrophobic Balance:
      Fabrication of Robust Biomolecular Immobilization Platforms.
AB  - Fabrication of hydrophilic polymeric nanofibers that undergo facile and selective
      functionalization through metal catalyst-free Diels-Alder "click" reaction in
      aqueous environment is outlined. Electrospinning of copolymers containing an
      electron-rich furan moiety, hydrophobic methyl methacrylate units and hydrophilic
      poly(ethylene glycol)s as side chains provide specifically functionalizable yet
      antibiofouling fibers that remain stable in aqueous media due to appropriate
      hydrophobic hydrophilic balance. Efficient functionalization of these nanofibers
      is accomplished through the Diels-Alder reaction by exposing them to maleimide
      containing molecules and ligands. Diels-Alder conjugation based functionalization
      is demonstrated through attachment of fluorescein-maleimide and a maleimide
      tethered biotin ligand. Biotinylated nanofibers were utilized to mediate
      immobilization of the protein streptavidin, as well as streptavidin coated
      quantum dots. Facile fabrication from readily available polymers and their
      effective functionalization under mild and reagent-free conditions in aqueous
      media make these "clickable" nanofibers attractive candidates as functionalizable
      scaffolds for various biomedical applications. 

PMID- 25844803
TI  - Minimal conductance-based model of auditory coincidence detector neurons.
AB  - Sound localization is a fundamental sensory function of a wide variety of
      animals. The interaural time difference (ITD), an important cue for sound
      localization, is computed in the auditory brainstem. In our previous modeling
      study, we introduced a two-compartment Hodgkin-Huxley type model to investigate
      how cellular and synaptic specializations may contribute to precise ITD
      computation of the barn owl's auditory coincidence detector neuron. Although our
      model successfully reproduced fundamental physiological properties observed in
      vivo, it was unsuitable for mathematical analyses and large scale simulations
      because of a number of nonlinear variables. In the present study, we reduce our
      former model into three types of conductance-based integrate-and-fire (IF)
      models. We test their electrophysiological properties using data from published
      in vivo and in vitro studies. Their robustness to parameter changes and
      computational efficiencies are also examined. Our numerical results suggest that
      the single-compartment active IF model is superior to other reduced models in
      terms of physiological reproducibility and computational performance. This model
      will allow future theoretical studies that use more rigorous mathematical
      analysis and network simulations. 

PMID- 25844804
TI  - Colors for molecular masses: fusion of spectroscopy and mass spectrometry for
      identification of biomolecules.
AB  - We present an approach that integrates ultraviolet (UV) photofragmentation
      spectroscopy of cold ions with high-resolution Orbitrap mass spectrometry (MS)
      and uses mathematical analysis of the recorded 2D data arrays for structural
      identification of biomolecules. The synergy of the two orthogonal techniques
      makes these arrays unique fingerprints of molecular ions, enabling their reliable
      identifications. Using preliminary created libraries of fingerprints, the UV-MS
      approach was successfully applied for quantitative identification of exact
      isobaric molecules in their mixtures, which is one of the challenging cases for
      mass spectrometry. We also demonstrate how the UV and fragmentation mass spectra
      of unknown chemical components of a mixture can be recovered from its fingerprint
      even without a use of library. 

PMID- 25844805
TI  - Differential interactions of gelatin nanoparticles with the major lipids of model
      lung surfactant: changes in the lateral membrane organization.
AB  - There has been an increasing interest in the potential of nanomedicine,
      particularly in the use of nanoparticles between 10 nm and 1 MUm in diameter as
      drug delivery vehicles. For pulmonary drug delivery, it is important to
      understand the effect of polymeric nanoparticles on the lung surfactant in order
      to optimize the carriers by reducing their potential toxicological effects. This
      work presents a biophysical study of the impact of gelatin nanoparticles on
      packing and lateral organization of simple and complex lipid layers containing
      the major components of lung surfactant. Zwitterionic phosphatidylcholines,
      negatively charged phosphatidylglycerols, and the sterol cholesterol were
      employed in the models. In addition, the impact of acyl chain length was
      investigated. Packing was determined by surface pressure-area isotherms, whereas
      direct imaging of the surfactant at the air-water interface was performed using
      Brewster angle microscopy. Our results indicate minor changes in the surface
      pressure-area isotherms but concomitantly significant effects on the lateral
      organization of the monolayers upon nanoparticle addition. The data also suggest
      differential interactions of nanoparticles with the major lipid classes. Gelatin
      nanoparticles interact stronger with negatively charged phosphatidyl-glycerols
      compared to zwitterionic phosphatidyl-cholines. Furthermore, charge distribution
      depending on the molar lipid ratio and acyl chain saturation is important as
      well. Even cholesterol, whose concentration is low compared to other components,
      plays an important role in nanoparticle interactions. 

PMID- 25844806
TI  - Flexible lab-tailored cut-offs for suitability of formalin-fixed tumor samples
      for diagnostic mutational analyses.
AB  - The selection of proper tissues from formalin-fixed and paraffin-embedded tumors
      before diagnostic molecular testing is responsibility of the pathologist and
      represents a crucial step to produce reliable test results. The international
      guidelines suggest two cut-offs, one for the percentage and one for the number of
      tumor cells, in order to enrich the tumor content before DNA extraction. The aim
      of the present work was two-fold: to evaluate to what extent a low percentage or
      absolute number of tumor cells can be qualified for somatic mutation testing; and
      to determine how assay sensitivities can guide pathologists towards a better
      definition of morphology-based adequacy cut-offs. We tested 1797 tumor specimens
      from melanomas, colorectal and lung adenocarcinomas. Respectively, their BRAF, K
      RAS and EGFR genes were analyzed at specific exons by mutation-enriched PCR,
      pyrosequencing, direct sequencing and real-time PCR methods. We demonstrate that
      poorly cellular specimens do not modify the frequency distribution of either
      mutated or wild-type DNA samples nor that of specific mutations. This observation
      suggests that currently recommended cut-offs for adequacy of specimens to be
      processed for molecular assays seem to be too much stringent in a laboratory
      context that performs highly sensitive routine analytical methods. In conclusion,
      new cut-offs are needed based on test sensitivities and documented tumor
      heterogeneity. 

PMID- 25844807
TI  - Highly Cyclable Lithium-Sulfur Batteries with a Dual-Type Sulfur Cathode and a
      Lithiated Si/SiOx Nanosphere Anode.
AB  - Lithium-sulfur batteries could become an excellent alternative to replace the
      currently used lithium-ion batteries due to their higher energy density and lower
      production cost; however, commercialization of lithium-sulfur batteries has so
      far been limited due to the cyclability problems associated with both the sulfur
      cathode and the lithium-metal anode. Herein, we demonstrate a highly reliable
      lithium-sulfur battery showing cycle performance comparable to that of lithium
      ion batteries; our design uses a highly reversible dual-type sulfur cathode
      (solid sulfur electrode and polysulfide catholyte) and a lithiated Si/SiOx
      nanosphere anode. Our lithium-sulfur cell shows superior battery performance in
      terms of high specific capacity, excellent charge-discharge efficiency, and
      remarkable cycle life, delivering a specific capacity of ~750 mAh g(-1) over 500
      cycles (85% of the initial capacity). These promising behaviors may arise from a
      synergistic effect of the enhanced electrochemical performance of the newly
      designed anode and the optimized layout of the cathode. 

PMID- 25844808
TI  - Dose-dependent effects of morphine exposure on mRNA and microRNA (miR) expression
      in hippocampus of stressed neonatal mice.
AB  - Morphine is used to sedate critically ill infants to treat painful or stressful
      conditions associated with intensive care. Whether neonatal morphine exposure
      affects microRNA (miR) expression and thereby alters mRNA regulation is unknown.
      We tested the hypothesis that repeated morphine treatment in stress-exposed
      neonatal mice alters hippocampal mRNA and miR expression. C57BL/6 male mice were
      treated from postnatal day (P) 5 to P9 with morphine sulfate at 2 or 5 mg/kg ip
      twice daily and then exposed to stress consisting of hypoxia (100% N2 1 min and
      100% O2 5 min) followed by 2h maternal separation. Control mice were untreated
      and dam-reared. mRNA and miR expression profiling was performed on hippocampal
      tissues at P9. Overall, 2 and 5 mg/kg morphine treatment altered expression of a
      total of 150 transcripts (>1.5 fold change, P<0.05) from which 100 unique mRNAs
      were recognized (21 genes were up- and 79 genes were down-regulated), and 5 mg/kg
      morphine affected 63 mRNAs exclusively. The most upregulated mRNAs were fidgetin,
      arginine vasopressin, and resistin-like alpha, and the most down-regulated were
      defensin beta 11, aquaporin 1, calmodulin-like 4, chloride intracellular channel
      6, and claudin 2. Gene Set Enrichment Analysis revealed that morphine treatment
      affected pathways related to cell cycle, membrane function, signaling,
      metabolism, cell death, transcriptional regulation, and immune response. Morphine
      decreased expression of miR-204-5p, miR-455-3p, miR-448-5p, and miR-574-3p. Nine
      morphine-responsive mRNAs that are involved in neurodevelopment,
      neurotransmission, and inflammation are predicted targets of the aforementioned
      differentially expressed miRs. These data establish that morphine produces dose
      dependent changes in both hippocampal mRNA and miR expression in stressed
      neonatal mice. If permanent, morphine-mediated neuroepigenetic effects may affect
      long-term hippocampal function, and this provides a mechanism for the neonatal
      morphine-related impairment of adult learning. 

PMID- 25844810
TI  - Improving environmental risk assessment of human pharmaceuticals.
AB  - This paper presents 10 recommendations for improving the European Medicines
      Agency's guidance for environmental risk assessment of human pharmaceutical
      products. The recommendations are based on up-to-date, available science in
      combination with experiences from other chemical frameworks such as the REACH
      legislation for industrial chemicals. The recommendations concern: expanding the
      scope of the current guideline; requirements to assess the risk for development
      of antibiotic resistance; jointly performed assessments; refinement of the test
      proposal; mixture toxicity assessments on active pharmaceutical ingredients with
      similar modes of action; use of all available ecotoxicity studies; mandatory
      reviews; increased transparency; inclusion of emission data from production; and
      a risk management option. We believe that implementation of our recommendations
      would strengthen the protection of the environment and be beneficial to society.
      Legislation and guidance documents need to be updated at regular intervals in
      order to incorporate new knowledge from the scientific community. This is
      particularly important for regulatory documents concerning pharmaceuticals in the
      environment since this is a research field that has been growing substantially in
      the last decades. 

PMID- 25844809
TI  - MET gene copy number alterations and expression of MET and hepatocyte growth
      factor are potential biomarkers in angiosarcomas and undifferentiated pleomorphic
      sarcomas.
AB  - Soft tissue sarcomas are a heterogeneous group of tumors with many different
      subtypes. In 2014 an estimated 12,020 newly diagnosed cases and 4,740 soft tissue
      sarcoma related deaths can be expected in the United States. Many soft tissue
      sarcomas are associated with poor prognosis and therapeutic options are often
      limited. The evolution of precision medicine has not yet fully reached the
      clinical treatment of sarcomas since therapeutically tractable genetic changes
      have not been comprehensively studied so far. We analyzed a total of 484 adult
      type malignant mesenchymal tumors by MET fluorescence in situ hybridization and
      MET and hepatocyte growth factor immunohistochemistry. Eleven different entities
      were included, among them the most common and clinically relevant subtypes and
      tumors with specific translocations or complex genetic changes. MET protein
      expression was observed in 2.6% of the cases, all of which were either
      undifferentiated pleomorphic sarcomas or angiosarcomas, showing positivity rates
      of 14% and 17%, respectively. 6% of the tumors showed hepatocyte growth factor
      overexpression, mainly seen in undifferentiated pleomorphic sarcomas and
      angiosarcomas, but also in clear cell sarcomas, malignant peripheral nerve sheath
      tumors, leiomyosarcomas and gastrointestinal stromal tumors. MET and hepatocyte
      growth factor overexpression were significantly correlated and may suggest an
      autocrine activation in these tumors. MET FISH amplification and copy number gain
      were present in 4% of the tumors (15/413). Two samples, both undifferentiated
      pleomorphic sarcomas, fulfilled the criteria for high level amplification of MET,
      one undifferentiated pleomorphic sarcoma reached an intermediate level copy
      number gain, and 12 samples of different subtypes were categorized as low level
      copy number gains for MET. Our findings indicate that angiosarcomas and
      undifferentiated pleomorphic sarcomas rather than other frequent adult-type
      sarcomas should be enrolled in screening programs for clinical trials with MET
      inhibitors. The screening methods should include both in situ hybridization and
      immunohistochemistry. 

PMID- 25844811
TI  - Getting the message across: outcomes and risk profiles by awareness levels of the
      "measure-up" obesity prevention campaign in Australia.
AB  - BACKGROUND: Obesity campaign evaluations have used campaign awareness to assess
      impact, yet have not compared unprompted campaign recallers, with prompted
      recallers and those with no campaign recall. Using data from an Australian mass
      media obesity prevention campaign linking waist circumference and chronic disease
      we examined whether those with different degrees of campaign recall are distinct
      groups demographically and for subsequent campaign effects. METHODS: A national
      cross-sectional telephone survey of randomly selected adults aged 18 to 65 years
      was conducted post- campaign (n = 2812) covering campaign recall, self-reported
      diet and physical activity (PA) and waist-measuring knowledge, behaviours and
      intentions to make lifestyle changes. Respondents were divided into three groups
      indicating campaign recall: Unprompted Recallers (n=1154); Prompted Recallers
      (n=1284); and No Recallers (n=374) and compared on demographic, knowledge, and
      behavioural risk factors for obesity/chronic disease. RESULTS: Unprompted
      Recallers were more likely to speak English at home (p<.001), be in the primary
      campaign target group (25-45 years with children) (p<0.001) than the other two
      groups and to be university educated and female than the Prompted Recall group
      only (p=0.001). Unprompted Recallers had better knowledge about recommended waist
      circumference (p<.001), fruit (p=0.004), vegetable (p<0.001) and PA guidelines
      (p<0.001) than both the other groups. The No Recall group was less likely than
      the other two to be overweight/obese (46% vs 55%, p=0.020 and 54%, p=0.037),
      comparable on meeting fruit consumption and PA guidelines but more likely to meet
      vegetable intake recommendations (than Unprompted Recallers only). CONCLUSIONS:
      Unprompted recallers were more knowledgeable about campaign messages; behaviour
      change and intentions to change were stronger for the two recall groups compared
      with the No Recall group but not different between them. The current analysis
      revealed subtle differences in campaign exposure and/or attendance by different
      demographic subgroups that would not be apparent in a simple aware/unaware
      dichotomy.

PMID- 25844812
TI  - Internet sex-seeking is inconsistently linked with sexual risk in men who have
      sex with men: systematic review of within-subjects comparisons.
AB  - Background Internet sex-seeking has been associated at the person level with
      sexual risk. However, the most robust method of encounter-level inference to
      determine associations between internet sex-seeking and sexual risk is to compare
      encounters against each other. We systematically reviewed within-subjects
      comparisons of sexual encounters that tested associations between internet sex
      seeking and sexual risk in men who have sex with men. METHODS: We systematically
      searched databases on 9 July 2013, then screened records and full-text articles
      in duplicate and independently. Studies were synthesised narratively. RESULTS:
      Four studies were included. Although studies were generally of high quality, the
      findings were inconsistent and did not show clear evidence of a relationship
      between internet sex-seeking and sexual risk. CONCLUSIONS: Further research in
      internet sex-seeking among men who have sex with men is required, particularly as
      internet-enabled sexual sociality continues to evolve. Internet-based health
      promotion may wish to target person-level features instead of encounter-specific
      characteristics.

PMID- 25844813
TI  - Simple analytical expression for the peak-frequency shifts of plasmonic
      resonances for sensing.
AB  - We derive a closed-form expression that accurately predicts the peak frequency
      shift and broadening induced by tiny perturbations of plasmonic nanoresonators
      without critically relying on repeated electrodynamic simulations of the spectral
      response of nanoresonator for various locations, sizes, or shapes of the
      perturbing objects. In comparison with other approaches of the same kind, the
      force of the present approach is that the derivation is supported by a
      mathematical formalism based on a rigorous normalization of the resonance modes
      of nanoresonators consisting of lossy and dispersive materials. Accordingly,
      accurate predictions are obtained for a large range of nanoparticle shapes and
      sizes used in various plasmonic nanosensors even beyond the quasistatic limit.
      The expression gives quantitative insight and, combined with an open-source code,
      provides accurate and fast predictions that are ideally suited for preliminary
      designs or for interpretation of experimental data. It is also valid for photonic
      resonators with large mode volumes. 

PMID- 25844814
TI  - Distinct role of hydration water in protein misfolding and aggregation revealed
      by fluctuating thermodynamics analysis.
AB  - Protein aggregation in aqueous cellular environments is linked to diverse human
      diseases. Protein aggregation proceeds through a multistep process initiated by
      conformational transitions, called protein misfolding, of monomer species toward
      aggregation-prone structures. Various forms of aggregate species are generated
      through the association of misfolded monomers including soluble oligomers and
      amyloid fibrils. Elucidating the molecular mechanisms and driving forces involved
      in the misfolding and subsequent association has been a central issue for
      understanding and preventing protein aggregation diseases such as Alzheimer's,
      Parkinson's, and type II diabetes. In this Account, we provide a thermodynamic
      perspective of the misfolding and aggregation of the amyloid-beta (Abeta) protein
      implicated in Alzheimer's disease through the application of fluctuating
      thermodynamics. This approach "dissects" the conventional thermodynamic
      characterization of the end states into the one of the fluctuating processes
      connecting them, and enables one to analyze variations in the thermodynamic
      functions that occur during the course of protein conformational changes. The
      central quantity in this approach is the solvent-averaged effective energy, f =
      Eu + Gsolv, comprising the protein potential energy (Eu) and the solvation free
      energy (Gsolv), whose time variation reflects the protein dynamics on the free
      energy landscape. Protein configurational entropy is quantified by the magnitude
      of fluctuations in f. We find that misfolding of the Abeta monomer when released
      from a membrane environment to an aqueous phase is driven by favorable changes in
      protein potential energy and configurational entropy, but it is also accompanied
      by an unfavorable increase in solvation free energy. The subsequent dimerization
      of the misfolded Abeta monomers occurs in two steps. The first step, where two
      widely separated monomers come into contact distance, is driven by water-mediated
      attraction, that is, by a decrease in solvation free energy, harnessing the
      monomer solvation free energy earned during the misfolding. The second step,
      where a compact dimer structure is formed, is driven by direct protein-protein
      interactions, but again it is accompanied by an increase in solvation free
      energy. The increased solvation free energy of the dimer will function as the
      driving force to recruit another Abeta protein in the approach stage of
      subsequent oligomerizations. The fluctuating thermodynamics analysis of the
      misfolding and dimerization of the Abeta protein indicates that the interaction
      of the protein with surrounding water plays a critical role in protein
      aggregation. Such a water-centric perspective is further corroborated by
      demonstrating that, for a large number of Abeta mutants and mutants of other
      protein systems, the change in the experimental aggregation propensity upon
      mutation has a significant correlation with the protein solvation free energy
      change. We also find striking discrimination between the positively and
      negatively charged residues on the protein surface by surrounding water
      molecules, which is shown to play a crucial role in determining the protein
      aggregation propensity. We argue that the protein total charge dictates such
      striking behavior of the surrounding water molecules. Our results provide new
      insights for understanding and predicting the protein aggregation propensity,
      thereby offering novel design principles for producing aggregation-resistant
      proteins for biotherapeutics. 

PMID- 25844816
TI  - Cavitands incorporating a Lewis acid dinickel chelate function as receptors for
      halide anions.
AB  - The halide binding properties of the cavitand [Ni2(L(Me2H4))](2+) (4) are
      reported. Cavitand 4 exhibits a chelating N3Ni(MU-S)2NiN3 moiety with two square
      pyramidal Ni(II)N3S2 units situated in an anion binding pocket of ~4 A diameter
      formed by the organic backbone of the (L(Me2H4))(2-) macrocycle. The receptor
      reacts with fluoride, chloride (in MeCN/MeOH), and bromide (in MeCN) ions to
      afford an isostructural series of halogenido-bridged complexes [Ni2(L(Me2H4))(MU
      Hal)](+) (Hal = F(-) (5), Cl(-) (6), and Br(-) (7)) featuring a N3Ni(MU-S)2(MU
      Hal)NiN3 core structure. No reaction occurs with iodide or other polyatomic
      anions (ClO4(-), NO3(-), HCO3(-), H2PO4(-), HSO4(-), SO4(2-)). The binding events
      are accompanied by discrete UV-vis spectral changes, due to a switch of the
      coordination geometry from square-pyramidal (N3S2 donor set in 4) to octahedral
      in the halogenido-bridged complexes (N3S2Hal donor environment in 5-7). In
      MeCN/MeOH (1/1 v/v) the log K11 values for the 1:1 complexes are 7.77(9) (F(-)),
      4.06(7) (Cl(-)), and 2.0(1) (Br(-)). X-ray crystallographic analyses for
      4(ClO4)2, 4(I)2, 5(F), 6(ClO4), and 7(Br) and computational studies reveal a
      significant increase of the intramolecular distance between two propylene groups
      at the cavity entrance upon going from F(-) to I(-) (for the DFT computed
      structure). In case of the receptor 4 and fluorido-bridged complex 5, the
      corresponding distances are nearly identical. This indicates a high degree of
      preorganization of the [Ni2(L(Me2H4))](2+) receptor and a size fit mismatch of
      the receptor binding cavity for anions larger than F(-). 

PMID- 25844815
TI  - Determining particulate matter and black carbon exfiltration estimates for
      traditional cookstove use in rural Nepalese village households.
AB  - A majority of black carbon (BC) emitted to the atmosphere in the Indo-Gangetic
      Plain (IGP) region is from burning biomass fuel used in traditional, open-design
      cookstoves. However, BC and particulate matter (PM) household emissions are not
      well characterized. Household emission information is needed to develop emission
      profiles to validate regional climate change models and serve as a baseline for
      assessing the impact of adopting improved stove technology. This paper presents
      field-based household PM and BC exfiltration (amount exiting) estimates from
      village homes in rural Nepal that utilize traditional, open-design cookstoves.
      Use of these stoves resulted in a 26% mean PM exfiltration, ranging from 6% to
      58%. This is a significant departure from an 80% estimate cited in previous
      reports. Furthermore, having a window/door resulted in an 11% increase in
      exfiltration when an opening was present, while fuel type had a marginally
      significant impact on emission. Air-exchange rates (AER) were determined with
      average (95% CI) AER of 12 (10-14) per hour, consistent with previous studies. In
      addition, BC to PM2.5 mass-ratio composition during cooking was ascertained, with
      an average (95% CI) of 31% (24-39), agreeing with previous biomass fuel emission
      composition literature. 

PMID- 25844817
TI  - Cowpox Helped Against Smallpox; Will the Goat Lentivirus (Caprine Arthritis
      Encephalitis Virus) Help Against HIV-1?

PMID- 25844818
TI  - A multicenter, open-label, Phase 1 study evaluating the safety and tolerability
      of pegaspargase in combination with gemcitabine in advanced metastatic solid
      tumors and lymphoma.
AB  - PURPOSE: To evaluate the maximum tolerated dose, safety profile,
      pharmacokinetics, and pharmacodynamics of pegaspargase (PEG-ASP) in combination
      with gemcitabine in patients with advanced metastatic solid tumors and lymphoma.
      METHODS: We conducted a multicenter, open label, nonrandomized, Phase 1 dose
      escalation study designed to evaluate up to 10 cohorts of patients with advanced
      or metastatic solid tumors and lymphoma. Seventeen patients were treated with of
      PEG-ASP in combination with gemcitabine. RESULTS: The study was terminated early
      because the doses for PEG-ASP suggested for de-escalation were predicted not to
      provide desired sustained asparaginase concentrations based on the analysis of
      treated patients.

PMID- 25844819
TI  - Solution-mediated selective nanosoldering of carbon nanotube junctions for
      improved device performance.
AB  - As-grown randomly aligned networks of carbon nanotubes (CNTs) invariably suffer
      from limited transport properties due to high resistance at the crossed junctions
      between CNTs. In this work, Joule heating of the highly resistive CNT junctions
      is carried out in the presence of a spin-coated layer of a suitable chemical
      precursor. The heating triggers thermal decomposition of the chemical precursor,
      tris(dibenzylideneacetone)dipalladium (Pd2(dba)3), and causes local deposition of
      Pd nanoparticles at the CNT junctions, thereby improving the on/off current ratio
      and mobility of CNT network devices by an average factor of ~6. This process can
      be conducted either in air or under vacuum depending on the characteristics of
      the precursor species. The solution-mediated nanosoldering process is simple,
      fast, scalable with manufacturing techniques, and extendable to the
      nanodeposition of a wide variety of materials. 

PMID- 25844820
TI  - Socio-Demographic Factors, Social Support, Quality of Life, and HIV/AIDS in
      Ghana.
AB  - The increase in the access to biomedical interventions for people living with
      HIV/AIDS in the developing world has not been adequately matched with the
      requisite psychosocial treatments to help improve the effectiveness of biomedical
      interventions. Therefore, in this study the author seeks to determine whether
      socio-demographic characteristics and social support are associated with quality
      of life in individuals diagnosed with HIV/AIDS in Ghana. A convenience sample of
      300 HIV/AIDS support group members was obtained via cross-sectional design
      survey. The Medical Outcome Studies (MOS) HIV Health Survey, the MOS Social
      Support Survey (MOS-SSS), and demographic questionnaire instruments were used to
      assess quality of life, social support, and demographic information respectively.
      Multiple regression analysis showed that there was a positive association between
      overall social support and overall quality of life (r = .51). It also showed that
      being younger, male, attending support group meetings for over a year, and having
      >= 13 years of schooling related to higher quality of life. Implications of the
      findings for practice, policy, and research in Ghana and the rest of the
      developing world are discussed.

PMID- 25844822
TI  - Stage IIIC Endometrial Cancer: Relapse and Survival Outcomes in Women Treated
      With Pelvic or Extended Field Para-Aortic Nodal Radiation Therapy.
AB  - PURPOSE: The optimal radiation (RT) volume for node-positive endometrial cancer
      is controversial. This study evaluates clinical outcomes in patients with stage
      IIIC, N1 endometrial cancer who received RT to the pelvis (PV RT) or pelvis plus
      para-aortic nodes (PV-PAN RT). METHODS: Overall, there were 89 women with stage
      IIIC endometrial cancer. Of these, 57 women had N1-only disease, forming the
      study cohort. Clinicopathologic characteristics, recurrence rates, endometrial
      cancer-specific survival (ECSS), and overall survival (OS) were examined among
      patients treated with pelvic RT (n=23) compared with pelvic plus para-aortic RT
      (n=34). Multivariable analysis of ECSS and OS was performed using Cox regression
      modeling. RESULTS: Median follow-up was 5.1 years. Adjuvant chemotherapy was used
      in 51/57 (89%) of N1 cases. Women with N1 disease who received PV-PAN RT compared
      with PV RT experienced lower recurrence (26% vs. 52%, P=0.06) and higher survival
      rates (5 y ECSS 81.5% vs. 47.0%, P=0.04 and OS 79.1% vs. 47.0%, P=0.01). On
      multivariable analysis, RT volume was not significantly associated with OS,
      whereas chemotherapy was associated with improved ECSS and OS. CONCLUSIONS: RT
      conferred excellent local control, whereas chemotherapy was associated with
      improved survival in women with N1 endometrial cancer. Distant relapse remains
      the most common site of recurrence despite chemotherapy.

PMID- 25844823
TI  - Eligibility of Metastatic Pancreatic Cancer Patients for First-Line Palliative
      Intent nab-Paclitaxel Plus Gemcitabine Versus FOLFIRINOX.
AB  - OBJECTIVES: The PRODIGE and MPACT trials showed superiority of FOLFIRINOX and nab
      paclitaxel plus gemcitabine (NG) over gemcitabine alone, respectively. However,
      both had strict inclusion criteria. We sought to determine the characteristics of
      patients with metastatic pancreatic cancer (MPC) which inform the appropriateness
      of first-line chemotherapy FOLFIRINOX and NG in routine practice. MATERIALS AND
      METHODS: Patients with MPC who initiated palliative chemotherapy with gemcitabine
      from 2000 to 2011 at the British Columbia Cancer Agency were identified.
      Clinicopathologic variables and outcomes were retrospectively collected and
      compared among groups. Eligibility criteria for each regimen were in accordance
      with the respective pivotal phase III trials. RESULTS: A total of 473 patients
      were included: 25% of the patients were eligible for FOLFIRINOX versus 45% for
      NG. Main reasons for FOLFIRINOX ineligibility were Eastern Cooperative Oncology
      Group (ECOG) performance status (PS)>=2 (56.5%), age older than 75 years (19.0%),
      and bilirubin>1.5* upper limit of normal (18.6%), whereas those for NG
      ineligibility were bilirubin > upper limit of normal (24.5%), ECOG PS>=3 (14.6%),
      and cardiac dysfunction (13.8%). Univariate analyses revealed that FOLFIRINOX and
      NG-eligible patients had longer median overall survival than their respective
      ineligible group (8.6 vs. 4.7 mo, P<0.001; 6.7 vs. 4.9 mo, P=0.008,
      respectively). After accounting for ECOG PS in the multivariate model, however,
      eligibility for either FOLFIRINOX or NG no longer predicted for better overall
      survival. CONCLUSIONS: The majority of patients with MPC are not candidates to
      either NG or FOLFIRINOX due to restrictive eligibility requirements. Specific
      trials addressing the unmet needs of protocol ineligible patients are warranted.

PMID- 25844824
TI  - Factors Associated With Guideline-recommended KRAS Testing in Colorectal Cancer
      Patients: A Population-based Study.
AB  - OBJECTIVES: Response to epidermal growth factor receptor inhibitors is poorer
      among stage IV colorectal cancer (CRC) patients with KRAS mutations; thus KRAS
      testing is recommended before treatment. KRAS testing was collected by
      Surveillance, Epidemiology, and End Results (SEER) registries for 2010 CRC cases,
      and our goal was to provide the first population-based estimates of testing in
      the United States. METHODS: SEER CRC cases diagnosed in 2010 were evaluated
      (n=30,351). chi tests and logistic regression were conducted to determine patient
      characteristics associated with KRAS testing, stratified by stages I-III versus
      stage IV. Log-rank tests were used to examine survival by testing status.
      RESULTS: KRAS testing among stage IV cases ranged from 39% in New Mexico to 15%
      in Louisiana. In the model, younger age, being married, living in a metropolitan
      area, and having primary site surgery were associated with greater odds of
      receiving KRAS testing. Those who received testing had significantly better
      survival than those who did not (P<0.0001). Among those who received testing,
      there was no significant difference in survival by mutated versus wild-type KRAS.
      Five percent of stage I-III cases received testing. CONCLUSIONS: Wide variation
      in documented KRAS testing for stage IV CRC patients exists among SEER
      registries. Age remained highly significant in multivariate models, suggesting
      that it plays an independent role in the patient and/or provider decision to be
      tested. Further research is needed to determine drivers of variation in testing,
      as well as reasons for testing in stage I-III cases where it is not recommended.

PMID- 25844825
TI  - Seven-Year Outcomes Following Accelerated Partial Breast Irradiation Stratified
      by ASTRO Consensus Groupings.
AB  - OBJECTIVES: Limited long-term data exist regarding outcomes for patients treated
      with accelerated partial breast irradiation (APBI), particularly, when stratified
      by American Society for Radiation Oncology (ASTRO) Consensus Statement (CS) risk
      groups. The purpose of this analysis is to present 5- and 7-year outcomes
      following APBI based on CS groupings. MATERIALS AND METHODS: A total of 690
      patients with early-stage breast cancer underwent APBI from 1993 to 2012,
      receiving interstitial brachytherapy (n=195), balloon-based brachytherapy
      (n=290), or 3-dimensional conformal radiotherapy (n=205) at a single institution.
      Patients were stratified into suitable, cautionary, and unsuitable groups with 5
      year outcomes analyzed. Seven-year outcomes were analyzed for a subset with
      follow-up of >=2 years (n=625). RESULTS: Median follow-up was 6.7 years (range,
      0.1 to 20.1 y). Patients assigned to cautionary and unsuitable categories were
      more likely to have high-grade tumors (21% to 25% vs. 9%, P=0.001), receive
      chemotherapy (15% to 38% vs. 6%, P<0.001), and have close/positive margins (9% to
      11% vs. 0%, P<0.001). There was no difference in ipsilateral breast tumor
      recurrence at 5 or 7 years: 2.2%, 1.2%, 2.8% at 5 years (P=0.57), and 2.2%, 1.9%,
      4.6% at 7 years (P=0.58) in the suitable, cautionary, and unsuitable groups,
      respectively. As compared with the suitable group, increased rates of distant
      metastases were noted for the unsuitable and cautionary groups at 5 years
      (P=0.04). CONCLUSIONS: No differences in rates of ipsilateral breast tumor
      recurrence were seen at 5 or 7 years when stratified by ASTRO CS groupings.
      Modest increases in distant recurrence were noted in the cautionary and
      unsuitable groups. These findings suggest that the ASTRO CS groupings stratify
      more for systemic recurrence and may not appropriately select patients for whole
      versus partial breast irradiation.

PMID- 25844821
TI  - Lansoprazole Is Associated with Worsening Asthma Control in Children with the
      CYP2C19 Poor Metabolizer Phenotype.
AB  - RATIONALE: Gastric acid blockade in children with asymptomatic acid reflux has
      not improved asthma control in published studies. There is substantial population
      variability regarding metabolism of and response to proton pump inhibitors based
      on metabolizer phenotype. How metabolizer phenotype affects asthma responses to
      acid blockage is not known. OBJECTIVES: To determine how metabolizer phenotype
      based on genetic analysis of CYP2C19 affects asthma control among children
      treated with a proton pump inhibitor. METHODS: Asthma control as measured by the
      Asthma Control Questionnaire (ACQ) and other questionnaires from a 6-month
      clinical trial of lansoprazole in children with asthma was analyzed for
      associations with surrogates of lansoprazole exposure (based on treatment
      assignment and metabolizer phenotype). Groups included placebo-treated children;
      lansoprazole-treated extensive metabolizers (EMs); and lansoprazole-treated poor
      metabolizers (PMs). Metabolizer phenotypes were based on CYP2C19 haplotypes.
      Carriers of the CYP2C19*2, *3, *8, *9, or *10 allele were PMs; carriers of two
      wild-type alleles were extensive metabolizers (EMs). MEASUREMENTS AND MAIN
      RESULTS: Asthma control through most of the treatment period was unaffected by
      lansoprazole exposure or metabolizer phenotype. At 6 months, PMs displayed
      significantly worsened asthma control compared with EMs (+0.16 vs. -0.13; P =
      0.02) and placebo-treated children (+0.16 vs. -0.23; P < 0.01). Differences in
      asthma control were not associated with changes in gastroesophageal reflux
      symptoms. Recent upper respiratory infection worsened asthma control, and this
      upper respiratory infection effect may be more pronounced among lansoprazole
      treated PMs. CONCLUSIONS: Children with the PM phenotype developed worse asthma
      control after 6 months of lansoprazole treatment for poorly controlled asthma.
      Increased exposure to proton pump inhibitor may worsen asthma control by altering
      responses to respiratory infections. Clinical trial registered with
      www.clinicaltrials.gov (NCT00604851).

PMID- 25844826
TI  - Mapping of SrTm4, a Recessive Stem Rust Resistance Gene from Diploid Wheat
      Effective to Ug99.
AB  - Race TTKSK (or Ug99) of Puccinia graminis f. sp. tritici, the causal agent of
      wheat stem rust, is a serious threat to wheat production worldwide. Diploid
      wheat, Triticum monococcum (genome Am), has been utilized previously for the
      introgression of stem rust resistance genes Sr21, Sr22, and Sr35. Multipathotype
      seedling tests of biparental populations demonstrated that T. monococcum
      accession PI 306540 collected in Romania contains a recessive resistance gene
      effective to all P. graminis f. sp. tritici races screened, including race TTKSK.
      We will refer to this gene as SrTm4, which is the fourth stem rust resistance
      gene characterized from T. monococcum. Using two mapping populations derived from
      crosses of PI 272557*PI 306540 and G3116*PI 306540, we mapped SrTm4 on chromosome
      arm 2AmL within a 2.1 cM interval flanked by sequence-tagged markers BQ461276 and
      DR732348, which corresponds to a 240-kb region in Brachypodium chromosome 5. The
      eight microsatellite and nine sequence-tagged markers linked to SrTm4 will
      facilitate the introgression and accelerate the deployment of SrTm4-mediated Ug99
      resistance in wheat breeding programs.

PMID- 25844827
TI  - Resurgence of Pseudoperonospora cubensis: The Causal Agent of Cucurbit Downy
      Mildew.
AB  - The downy mildew pathogen, Pseudoperonospora cubensis, which infects plant
      species in the family Cucurbitaceae, has undergone major changes during the last
      decade. Disease severity and epidemics are far more destructive than previously
      reported, and new genotypes, races, pathotypes, and mating types of the pathogen
      have been discovered in populations from around the globe as a result of the
      resurgence of the disease. Consequently, disease control through host plant
      resistance and fungicide applications has become more complex. This resurgence of
      P. cubensis offers challenges to scientists in many research areas including
      pathogen biology, epidemiology and dispersal, population structure and population
      genetics, host preference, host-pathogen interactions and gene expression,
      genetic host plant resistance, inheritance of host and fungicide resistance, and
      chemical disease control. This review serves to summarize the current status of
      this major pathogen and to guide future management and research efforts within
      this pathosystem. 

PMID- 25844828
TI  - Resistance Against Basil Downy Mildew in Ocimum Species.
AB  - Downy mildew, caused by the oomycete Peronospora belbahrii, is a devastating
      disease of sweet basil. In this study, 113 accessions of Ocimum species (83 Plant
      Introduction entries and 30 commercial entries) were tested for resistance
      against downy mildew at the seedling stage in growth chambers, and during three
      seasons, in the field. Most entries belonging to O. basilicum were highly
      susceptible whereas most entries belonging to O. americanum, O.
      kilimanadascharicum, O. gratissimum, O. campechianum, or O. tenuiflorum were
      highly resistant at both the seedling stage and the field. Twenty-seven highly
      resistant individual plants were each crossed with the susceptible sweet basil
      'Peri', and the F1 progeny plants were examined for disease resistance. The F1
      plants of two crosses were highly resistant, F1 plants of 24 crosses were
      moderately resistant, and F1 plants of one cross were susceptible, suggesting
      full, partial, or no dominance of the resistance gene(s), respectively. These
      data confirm the feasibility of producing downy mildew-resistant cultivars of
      sweet basil by crossing with wild Ocimum species. 

PMID- 25844829
TI  - Identifying risky drinking patterns over the course of Saturday evenings: An
      event-level study.
AB  - Gaining a better understanding of young adults' excessive drinking on nights out
      is crucial to ensure prevention efforts are effectively targeted. This study aims
      to identify Saturdays with similar evening drinking patterns and corresponding
      situation-specific and person-specific determinants. Growth mixture modeling and
      multilevel logistic regressions were based on 3,084 questionnaires completed by
      164 young adults on 514 evenings via the Internet-based cell phone optimized
      assessment technique (ICAT). The results showed that the 2-group solution best
      fitted the data with a "stable low" drinking pattern (64.0% of all evenings, 0.2
      drinks per hour on average, 1.5 drinks in total) and an "accelerated" drinking
      pattern (36.0%, increased drinking pace from about 1 drink per hour before 8 p.m.
      to about 2 drinks per hour after 10 p.m.; 11.5 drinks in total). The presence of
      more same-sex friends (ORwomen = 1.29, 95% CI [1.09-1.53]; ORmen = 1.35, 95% CI
      [1.15-1.58], engaging in predrinking (ORwomen = 2.80, 95% CI [1.35-5.81]; ORmen =
      3.78, 95% CI [1.67-8.55] and more time spent in drinking establishments among men
      (ORmen = 1.46, 95% CI [1.12-1.90] predicted accelerated drinking evenings.
      Accelerated drinking was also likely among women scoring high on coping motives
      at baseline (ORwomen = 2.40, 95% CI [1.43-4.03] and among men scoring high on
      enhancement motives (ORmen = 2.36, 95% CI [1.46-3.80]. To conclude, with a total
      evening consumption that is almost twice the threshold for binge drinking, the
      identified accelerated drinking pattern signifies a burden for individual and
      public health. Promoting personal goal setting and commitment, and reinforcing
      self-efficacy and resistance skills training appear to be promising strategies to
      impede the acceleration of drinking pace on Saturday evenings.

PMID- 25844830
TI  - Interaction of depressive symptoms and smoking abstinence on delay discounting
      rates.
AB  - Delay discounting and depressive symptomatology have strong connections with
      smoking. However, few studies have examined interactions across delay
      discounting, depressive symptoms, and smoking status. The primary goal of this
      secondary analysis was to assess the interrelations across these 3 variables
      among treatment-seeking smokers. Delay discounting and depressive symptoms were
      assessed in 95 smokers enrolled in a clinical trial for smoking cessation at
      intake and 6-month follow-up. Participants with and without depressive symptoms
      did not differ in their discounting rates neither at intake nor at 6-month follow
      up. However, delay discounting was significantly lower among abstainers at 6
      month follow-up, and changes in discounting associated with smoking status were
      more pronounced among participants with depressive symptoms. These results
      clarify the relationship between delay discounting and depressive symptoms among
      current and former smokers and suggest that the association between smoking
      abstinence and lower delay discounting is significantly greater among individuals
      with depressive symptoms versus those who do not have depressive symptomatology.

PMID- 25844832
TI  - Older adults who are at risk of driving under the influence: A latent class
      analysis.
AB  - Despite increasing rates of substance use among older adults, their risk of
      driving under the influence of alcohol and/or drugs (DUI) has received scant
      research attention. This study identified DUI risk profiles among individuals
      aged 50+ years based on their substance use patterns, previous DUI incidents, and
      previous arrests. This study's analytic sample of 11,188 individuals came from
      the public use data sets of the 2008 to 2012 National Survey on Drug Use and
      Health. Latent class analysis identified a 4-class model as the most
      parsimonious. Class 1 (63% of the analytic sample; lowest risk group) exhibited
      the lowest probabilities of substance use and trouble with law while Class 4 (9%
      of the sample; highest risk group) included binge/heavy drinkers who are also
      likely to use illicit drugs and had the highest probabilities of self-reported
      DUI and previous arrests. Class 2 (18.5%) and Class 3 (9.5%) exhibited low-to
      medium DUI risks. Class 4 had the highest proportions of Blacks and divorced or
      never married persons and had lowest education and income, poorest self-rated
      health, and highest rates of mental health problems of all classes. Screening for
      substance abuse and comorbid mental health conditions should be included in
      protocols for assessing older adults' driving safety. More effort is also needed
      to improve access to substance abuse treatment and address mental health problems
      among older adults at high risk for DUI.

PMID- 25844831
TI  - The interactive effects of emotion regulation and alcohol intoxication on lab
      based intimate partner aggression.
AB  - This study draws on Finkel and Eckhardt's (2013) I3 framework to examine the
      interactive effects of 2 emotion regulation strategies-anger rumination (an
      impellance factor) and reappraisal (an inhibition factor), and alcohol
      intoxication (a disinhibition factor)-on intimate partner aggression (IPA)
      perpetration as measured with an analogue aggression task. Participants were 69
      couples recruited from a large Midwestern university (total N = 138).
      Participants' trait rumination and reappraisal were measured by self-report.
      Participants were randomized individually to an alcohol or placebo condition,
      then recalled an anger event while using 1 of 3 randomly assigned emotion
      regulation conditions (rumination, reappraisal, or uninstructed). Following this,
      participants completed an analogue aggression task involving ostensibly assigning
      white noise blasts to their partner. Participants in the alcohol condition
      displayed greater IPA than participants in the placebo condition for provoked
      IPA, but not unprovoked IPA. Results also revealed interactions such that for
      those in the alcohol and rumination group, higher trait reappraisal was related
      to lower unprovoked IPA. For provoked IPA, higher trait rumination was related to
      greater IPA among those in the alcohol and rumination condition and those in the
      placebo and uninstructed condition. In general, results were consistent with I3
      theory, suggesting that alcohol disinhibits, rumination impels, and trait
      reappraisal inhibits IPA. The theoretical and clinical implications of these
      findings are discussed in the context of current knowledge about the influence of
      alcohol intoxication and emotion regulation strategies on IPA perpetration.

PMID- 25844833
TI  - Inaugural editorial.

PMID- 25844835
TI  - Correction to Frone and Trinidad (2014).

PMID- 25844834
TI  - Randomized controlled trial of brief alcohol screening and intervention for
      college students for heavy-drinking mandated and volunteer undergraduates: 12
      month outcomes.
AB  - This is the first randomized trial testing whether heavy-drinking undergraduates
      mandated to the Brief Alcohol Screening and Intervention for College Students
      (BASICS) program following a campus alcohol violation would benefit as much as
      heavy-drinking volunteers up to 1 year postintervention using control groups with
      high-risk drinkers to model disciplinary-related and naturalistic changes in
      drinking. Participants (61% male; 51% mandated; 84% Caucasian; M age = 20.14
      years) were screened for heavy drinking and randomized to BASICS (n = 115) or
      assessment-only control (n = 110). Outcome measures (drinking, alcohol problems)
      were collected at baseline, 4 weeks, 3, 6, and 12 months postintervention. At 4
      weeks postintervention, intent-to-treat multilevel longitudinal models showed
      that regardless of referral group (mandated or volunteer), BASICS significantly
      decreased weekly drinking, typical drinks, and peak drinks relative to controls
      (ds = .41-.92). BASICS had a large effect on decreases in alcohol problems (d =
      .87). At 12 months postintervention, BASICS participants (regardless of referral
      group) reported significantly fewer alcohol problems (d = .56) compared with
      controls. Significant long-term intervention gains for peak and typical drinks
      were sustained in both referral groups relative to controls (ds = .42; .11).
      Referral group had no significant main effect and did not interact with
      intervention condition to predict outcomes. Given that BASICS was associated with
      less drinking and fewer alcohol problems (even among heavier drinking mandated
      students up to 1 year postintervention), provision of BASICS-style programs
      within disciplinary settings may help reduce heavy and problematic drinking among
      at-risk students. (PsycINFO Database Record 

PMID- 25844836
TI  - Immune response following postexposure rabies prophylaxis.

PMID- 25844837
TI  - Measuring zebrafish turning rate.
AB  - Zebrafish is becoming a popular animal model in preclinical research, and
      zebrafish turning rate has been proposed for the analysis of activity in several
      domains. The turning rate is often estimated from the trajectory of the fish
      centroid that is output by commercial or custom-made target tracking software run
      on overhead videos of fish swimming. However, the accuracy of such indirect
      methods with respect to the turning rate associated with changes in heading
      during zebrafish locomotion is largely untested. Here, we compare two indirect
      methods for the turning rate estimation using the centroid velocity or position
      data, with full shape tracking for three different video sampling rates. We use
      tracking data from the overhead video recorded at 60, 30, and 15 frames per
      second of zebrafish swimming in a shallow water tank. Statistical comparisons of
      absolute turning rate across methods and sampling rates indicate that, while
      indirect methods are indistinguishable from full shape tracking, the video
      sampling rate significantly influences the turning rate measurement. The results
      of this study can aid in the selection of the video capture frame rate, an
      experimental design parameter in zebrafish behavioral experiments where activity
      is an important measure. 

PMID- 25844838
TI  - Transcriptomic Analysis of Sinorhizobium meliloti and Medicago truncatula
      Symbiosis Using Nitrogen Fixation-Deficient Nodules.
AB  - The bacterium Sinorhizobium meliloti interacts symbiotically with legume plant
      hosts such as Medicago truncatula to form nitrogen-fixing root nodules. During
      symbiosis, plant and bacterial cells differentiate in a coordinated manner,
      resulting in specialized plant cells that contain nitrogen-fixing bacteroids.
      Both plant and bacterial genes are required at each developmental stage of
      symbiosis. We analyzed gene expression in nodules formed by wild-type bacteria on
      six plant mutants with defects in nitrogen fixation. We observed differential
      expression of 482 S. meliloti genes with functions in cell envelope homeostasis,
      cell division, stress response, energy metabolism, and nitrogen fixation. We
      simultaneously analyzed gene expression in M. truncatula and observed
      differential regulation of host processes that may trigger bacteroid
      differentiation and control bacterial infection. Our analyses of developmentally
      arrested plant mutants indicate that plants use distinct means to control
      bacterial infection during early and late symbiotic stages. 

PMID- 25844839
TI  - Effect of Oral Pathway on Charged Particles Deposition in Human Bronchial
      Airways.
AB  - BACKGROUND: In vitro studies to investigate the effect of charged particle
      deposition in the oral pathway of human adults have demonstrated substantial
      increases in deposition due to an induced charge effect. In the current study,
      charged particle deposition in the oral pathway was incorporated in the
      stochastic human airway generation model IDEAL (Inhalation, Deposition, and
      Exhalation of Aerosols in the Lung) to quantify their effect on bronchial airways
      deposition. METHODS: Calculation of increased oral deposition due to charged
      particles was performed by a modified version of IDEAL for oral pathway, whereas
      deposition in the bronchial airways was carried out by the already employed
      efficiency equation. Deposition calculations were performed for 3, 4.5, and 6 MUm
      particles at flow rates of 15 and 30 L/min. RESULTS: The enhancement in
      deposition is found to be 40 times higher in oral pathway and 6 times higher in
      bronchial airways for 3 MUm size particles carrying 2500 elementary charges. For
      particles larger than 3 MUm, deposition by impaction dominates over deposition by
      particle charges, and hence higher deposition in oral pathway is observed
      primarily due to impaction. As a consequence of this increased oral deposition,
      bronchial airways deposition decreases. CONCLUSION: By controlling breathing,
      aerosol properties, and electrostatic charge, targeted deposition in the human
      airways can be improved. Hence, charged particles can therefore be utilized to
      give better control on regional drug delivery in the lungs or to filter out toxic
      constituents.

PMID- 25844840
TI  - Current Therapeutic Options for Esophageal Motor Disorders as Defined by the
      Chicago Classification.
AB  - With the development of high-resolution manometry and specific metrics to
      characterize esophageal motility, the Chicago Classification has become the gold
      standard for the diagnosis of esophageal motor disorders. Major and significant
      disorders, that is, never observed in healthy subjects, are achalasia,
      esophagogastric junction outflow obstruction, distal esophageal spasm, absent
      peristalsis, and hypercontractile (Jackhammer) esophagus. Achalasia subtyping is
      relevant to predict the response to endoscopic and surgical therapies as several
      studies suggest that, pneumatic dilation is less effective than Heller myotomy,
      in type III achalasia. Peroral endoscopic myotomy, initially developed in expert
      centers, is a promising technique for the treatment of achalasia. The medical
      therapeutic options for distal esophageal spasm and hypercontractile esophagus
      are smooth muscle relaxants and pain modulators. Intraesophageal injection of
      botulinum toxin might be an interesting option for treatment of these disorders
      but further studies are required to determine the optimal injection protocol and
      the best candidates based on manometric patterns. The treatment of hypotensive
      motility disorders is disappointing and relies mainly on dietary and lifestyle
      changes as no effective esophageal prokinetic is currently available. 

PMID- 25844841
TI  - Low-dose Infliximab for Induction and Maintenance Treatment in Chinese Patients
      With Moderate to Severe Active Ulcerative Colitis.
AB  - GOAL: To evaluate the efficacy of low-dose (3.5 mg/kg) infliximab for induction
      and maintenance treatment in Chinese patients with ulcerative colitis.
      BACKGROUND: Treatment with 4 to 5 mg/kg of infliximab also proved to be effective
      in treating moderate to severe ulcerative colitis. At present there is no
      relevant study on the effectiveness of infliximab doses lower than 4 mg/kg in
      patients with ulcerative colitis. STUDY: A prospective, randomized, double-blind,
      placebo-controlled, and single-centered study was designed. A total of 123
      patients (from 17 provinces of China) with moderate to severe active ulcerative
      colitis despite treatment with concurrent drugs received placebo or low-dose (3.5
      mg/kg) or standard-dose (5 mg/kg) infliximab intravenously at weeks 0, 2, and 6
      and then every 8 weeks through week 22. Patients were followed up for 30 weeks.
      RESULTS: Overall, 73% and 78% of patients who received low-dose (3.5 mg/kg) and
      standard-dose (5 mg/kg) infliximab, respectively, had clinical responses at week
      8, as compared with 37% of patients who received placebo (P<0.01 for both
      comparisons with placebo). The number of patients who received low-dose (3.5
      mg/kg) or standard-dose (5 mg/kg) infliximab with a clinical response at week 30
      (63% and 66%, respectively) was more than the patients who received placebo (27%,
      P<0.01 for both comparisons). CONCLUSIONS: Chinese patients with moderate to
      severe active ulcerative colitis treated with low-dose (3.5 mg/kg) or standard
      dose (5 mg/kg) infliximab at weeks 0, 2, and 6 and every 8 weeks thereafter were
      more likely to have a clinical response at weeks 8 and 30 than those who received
      placebo.

PMID- 25844842
TI  - Anesthesiology: Attracting the Best New Science in the Specialty.

PMID- 25844843
TI  - Intraoperative Glycemic Control to Prevent Delirium after Cardiac Surgery:
      Steering a Course between Scylla and Charybdis.

PMID- 25844845
TI  - Noninvasive monitors of blood pressure in the critically ill: what are acceptable
      accuracy and precision?

PMID- 25844846
TI  - Anatomical basis of the various spread patterns around the femoral nerve in the
      inguinal region.

PMID- 25844847
TI  - The interplay of spatial attentional biases and mental codes in VSTM:
      Developmentally informed hypotheses.
AB  - What cognitive processes influence how well we maintain information in visual
      short-term memory (VSTM)? We used a developmentally informed design to delve into
      the interplay of top-down spatial biases with the nature of the internal memory
      codes, motivated by documented changes for both factors over childhood. Seven
      year-olds, 11-year-olds, and adults completed a VSTM task in which they decided
      whether a probe item had been present in a preceding memory array. Spatial cues
      guided participants' attention to the likely location of the to-be-probed item
      during maintenance. We manipulated the memoranda to contain either highly
      familiar items or unfamiliar abstract shapes. All participants benefited from
      cues during maintenance, although benefits were smaller for 7-year-olds than for
      older participants. Critically, attentional benefits interacted with the nature
      of the memoranda: Better VSTM maintenance was obtained for cued familiar items.
      Furthermore, attentional benefits for familiar items correlated with validated
      measures of visual, but not verbal, short-term and working memory span. These
      data demonstrate that, in addition to the efficiency with which top-down biases
      operate during maintenance, the available mental codes for to-be-remembered items
      influence VSTM and differentially so over childhood. Attentional biases during
      maintenance seem to operate more efficiently on mental representations that are
      more robust and can be retrieved more easily. More important, this interaction
      follows a quantitative development. The findings elucidate further the dynamic
      interplay between attentional control and VSTM across development.

PMID- 25844848
TI  - The interplay between values and aggression in adolescence: a longitudinal study.
AB  - Values, or the guiding standards of adolescents' lives, influence which behaviors
      are considered more justified than others. The relationship between values and
      social behavior has been established across many studies including the
      relationship of values and aggression. But only a few studies have examined these
      relationships among youth. Moreover, a question that remains open is the
      direction of these relationships. The present study examined the concurrent and
      longitudinal relations between values and peer nominated aggression in 3 time
      points with a 1-year interval (8th grade-10th grade) in a sample of 678 Israeli
      adolescents (51.2% girls). Students completed the Portrait Values Questionnaire
      (PVQ; Schwartz et al., 2001) and 6 items of peer nominations of aggression. As
      hypothesized, I found positive associations between aggression and self
      enhancement and openness to change values concurrently. Similarly, I obtained
      negative associations between aggression and self-transcendence and conservation
      values. Moreover, crossed-lagged models revealed that self-enhancement values
      were positively associated with aggression 1 year later. The association between
      aggression and future self-enhancement values, however, was not significant.
      Finally, I found mutual associations between self-transcendence values and
      aggression across time.

PMID- 25844849
TI  - Increases in maternal education and low-income children's cognitive and
      behavioral outcomes.
AB  - Although the strong link between maternal education and children's outcomes is
      one of the most well-established findings in developmental psychology (Reardon,
      2011; Sirin, 2005), less is known about how young, low-income children are
      influenced by their mothers completing additional education. In this research,
      longitudinal data from the Head Start Impact Study were used to explore the
      associations between increases in maternal education and Head Start eligible
      children's cognitive skills and behavioral problems in 1st grade. Propensity
      score weighting was used to identify a balanced comparison group of 1,362
      children whose mothers did not increase their education between baseline (when
      children were aged 3 or 4) and children's kindergarten year, who are similar on
      numerous covariates to the 262 children whose mothers did increase their
      education. Propensity-score weighted regression analyses indicated that increases
      in maternal education were positively associated with children's standardized
      cognitive scores, but also with higher teacher-reported externalizing behavioral
      problems in 1st grade. The increases in externalizing behavioral problems were
      larger for children whose mothers had less than a college degree at baseline.

PMID- 25844850
TI  - The developmental trajectory of intramaze and extramaze landmark biases in
      spatial navigation: An unexpected journey.
AB  - Adults learning to navigate to a hidden goal within an enclosed space have been
      found to prefer information provided by the distal cues of an environment, as
      opposed to proximal landmarks within the environment. Studies with children,
      however, have shown that 5- or 7-year-olds do not display any preference toward
      distal or proximal cues during navigation. This suggests that a bias toward
      learning about distal cues occurs somewhere between the age of 7 years and
      adulthood. We recruited 5- to 11-year-old children and an adult sample to explore
      the developmental profile of this putative change. Across a series of 3
      experiments, participants were required to navigate to a hidden goal in a virtual
      environment, the location of which was signaled by both extramaze and intramaze
      landmark cues. During testing, these cues were placed into conflict to assess the
      search preferences of participants. Consistent with previously reported findings,
      adults were biased toward using extramaze information. However, analysis of the
      data from children, which incorporated age as a continuous variable, suggested
      that older children in our sample were, in fact, biased toward using the
      intramaze landmark in our task. These findings suggest the bias toward using
      distal cues in spatial navigation, frequently displayed by adults, may be a
      comparatively late developing trait, and one that could supersede an initial
      developmental preference for proximal landmarks.

PMID- 25844851
TI  - Poverty, physical stature, and cognitive skills: Mechanisms underlying children's
      school enrollment in Zambia.
AB  - Past research suggests robust positive associations between household
      socioeconomic status and children's early cognitive development in Western
      countries. Relatively little is known about these relations in low-income country
      settings characterized by economic adversity, high prevalence of malnutrition and
      infectious disease, and relatively lower school enrollment. The present study
      develops and empirically evaluates an adapted model of early childhood
      development using a sample of 2,711 Zambian 6-year-olds. Early learning in and
      out of the home was found to explain much of the relation between socioeconomic
      status and children's cognitive skills, including language, nonverbal reasoning,
      and executive function. Child height-for-age (a proxy for overall nutritional
      status and health) was also predictive of children's cognitive skills and both
      early and on-time school enrollment. Implications for global child development,
      intervention, and future work are discussed.

PMID- 25844852
TI  - Synthesis, Structure, and Ethanol Gas Sensing Properties of In2O3 Nanorods
      Decorated with Bi2O3 Nanoparticles.
AB  - Bi2O3-decorated In2O3 nanorods were synthesized using a one-step process, and
      their structure, as well as the effects of decoration of In2O3 nanorods with
      Bi2O3 on the ethanol gas-sensing properties were examined. The multiple networked
      Bi2O3-decorated In2O3 nanorod sensor showed responses of 171-1774% at ethanol
      concentrations of 10-200 ppm at 200  degrees C. The responses of the Bi2O3
      decorated In2O3 nanorod sensor were stronger than those of the pristine-In2O3
      nanorod sensors by 1.5-4.9 times at the corresponding concentrations. The two
      sensors exhibited short response times and long recovery times. The optimal Bi
      concentration in the Bi2O3-decorated In2O3 nanorod sensor and the optimal
      operation temperature of the sensor were 20% and 200  degrees C, respectively.
      The Bi2O3-decorated In2O3 nanorod sensor showed selectivity for ethanol gas over
      other gases. The origin of the enhanced response, sensing speed, and selectivity
      for ethanol gas of the Bi2O3-decorated In2O3 nanorod sensor to ethanol gas is
      discussed. 

PMID- 25844854
TI  - Sport-Specific Training Targeting the Proximal Segments and Throwing Velocity in
      Collegiate Throwing Athletes.
AB  - CONTEXT: The ability to generate, absorb, and transmit forces through the
      proximal segments of the pelvis, spine, and trunk has been proposed to influence
      sport performance, yet traditional training techniques targeting the proximal
      segments have had limited success improving sport-specific performance.
      OBJECTIVE: To investigate the effects of a traditional endurance-training program
      and a sport-specific power-training program targeting the muscles that support
      the proximal segments and throwing velocity. DESIGN: Randomized controlled
      clinical trial. SETTING: University research laboratory and gymnasium. PATIENTS
      OR OTHER PARTICIPANTS: A total of 46 (age = 20 +/- 1.3 years, height = 175.7 +/-
      8.7 cm) healthy National Collegiate Athletic Association Division III female
      softball (n = 17) and male baseball (n = 29) players. INTERVENTION(S): Blocked
      stratification for sex and position was used to randomly assign participants to 1
      of 2 training groups for 7 weeks: a traditional endurance-training group (ET
      group; n = 21) or a power-stability-training group (PS group; n = 25). Mean
      Outcome Measure(s) : The change score in peak throwing velocity (km/h) normalized
      for body weight (BW; kilograms) and change score in tests that challenge the
      muscles of the proximal segments normalized for BW (kilograms). We used 2-tailed
      independent-samples t tests to compare differences between the change scores.
      RESULTS: The peak throwing velocity (ET group = 0.01 +/- 0.1 km/h/kg of BW, PS
      group = 0.08 +/- 0.03 km/h/kg of BW; P < .001) and muscle power outputs for the
      chop (ET group = 0.22 +/- 0.91 W/kg of BW, PS group = 1.3 +/- 0.91 W/kg of BW; P
      < .001) and lift (ET group = 0.59 +/- 0.67 W/kg of BW, PS group = 1.4 +/- 0.87
      W/kg of BW; P < .001) tests were higher at postintervention in the PT than in the
      ET group. CONCLUSIONS: An improvement in throwing velocity occurred
      simultaneously with measures of muscular endurance and power after a sport
      specific training regimen targeting the proximal segments.

PMID- 25844853
TI  - Using Accelerometer and Gyroscopic Measures to Quantify Postural Stability.
AB  - CONTEXT: Force platforms and 3-dimensional motion-capture systems provide an
      accurate method of quantifying postural stability. Substantial cost, space, time
      to administer, and need for trained personnel limit widespread use of
      biomechanical techniques in the assessment of postural stability in clinical or
      field environments. OBJECTIVE: To determine whether accelerometer and gyroscope
      data sampled from a consumer electronics device (iPad2) provide sufficient
      resolution of center-of-gravity (COG) movements to accurately quantify postural
      stability in healthy young people. DESIGN: Controlled laboratory study. SETTING:
      Research laboratory in an academic medical center. PATIENTS OR OTHER
      PARTICIPANTS: A total of 49 healthy individuals (age = 19.5 +/- 3.1 years, height
      = 167.7 +/- 13.2 cm, mass = 68.5 +/- 17.5 kg). INTERVENTION(S): Participants
      completed the NeuroCom Sensory Organization Test (SOT) with an iPad2 affixed at
      the sacral level. MAIN OUTCOME MEASURE(S): Primary outcomes were equilibrium
      scores from both systems and the time series of the angular displacement of the
      anteroposterior COG sway during each trial. A Bland-Altman assessment for
      agreement was used to compare equilibrium scores produced by the NeuroCom and
      iPad2 devices. Limits of agreement was defined as the mean bias (NeuroCom - iPad)
      +/- 2 standard deviations. Mean absolute percentage error and median difference
      between the NeuroCom and iPad2 measurements were used to evaluate how closely the
      real-time COG sway measured by the 2 systems tracked each other. RESULTS: The
      limits between the 2 devices ranged from -0.5 degrees  to 0.5 degrees  in SOT
      condition 1 to -2.9 degrees  to 1.3 degrees  in SOT condition 5. The largest
      absolute value of the measurement error within the 95% confidence intervals for
      all conditions was 2.9 degrees . The mean absolute percentage error analysis
      indicated that the iPad2 tracked NeuroCom COG with an average error ranging from
      5.87% to 10.42% of the NeuroCom measurement across SOT conditions. CONCLUSIONS:
      The iPad2 hardware provided data of sufficient precision and accuracy to quantify
      postural stability. Accuracy, portability, and affordability make using the iPad2
      a reasonable approach for assessing postural stability in clinical and field
      environments.

PMID- 25844855
TI  - Neural Excitability Alterations After Anterior Cruciate Ligament Reconstruction.
AB  - CONTEXT: Neuromuscular dysfunction is common after anterior cruciate ligament
      reconstruction (ACL-R). However, little is known about quadriceps spinal-reflex
      and descending corticomotor excitability after ACL-R. Understanding the effects
      of ACL-R on spinal-reflex and corticomotor excitability will help elucidate the
      origins of neuromuscular dysfunction. OBJECTIVE: To determine whether spinal
      reflex excitability and corticomotor excitability differed between the injured
      and uninjured limbs of patients with unilateral ACL-R and between these limbs and
      the matched limbs of healthy participants. DESIGN: Case-control study. SETTING:
      Laboratory. PATIENTS OR OTHER PARTICIPANTS: A total of 28 patients with
      unilateral ACL-R (9 men, 19 women; age = 21.28 +/- 3.79 years, height = 170.95 +/
      10.04 cm, mass = 73.18 +/- 18.02 kg, time after surgery = 48.10 +/- 36.17
      months) and 29 participants serving as healthy controls (9 men, 20 women; age =
      21.55 +/- 2.70 years, height = 170.59 +/- 8.93 cm, mass = 71.89 +/- 12.70 kg)
      volunteered. MAIN OUTCOME MEASURE(S): Active motor thresholds (AMTs) were
      collected from the vastus medialis (VM) using transcranial magnetic stimulation.
      We evaluated VM spinal reflexes using the Hoffmann reflex normalized to maximal
      muscle responses (H : M ratio). Voluntary quadriceps activation was measured with
      the superimposed-burst technique and calculated using the central activation
      ratio (CAR). We also evaluated whether ACL-R patients with high or low voluntary
      activation had different outcomes. RESULTS: The AMT was higher in the injured
      than in the uninjured limb in the ACL-R group (t27 = 3.32, P = .003) and in the
      matched limb of the control group (t55 = 2.05, P = .04). The H : M ratio was
      bilaterally higher in the ACL-R than the control group (F1,55 = 5.17, P = .03).
      The quadriceps CAR was bilaterally lower in the ACL-R compared with the control
      group (F1,55 = 10.5, P = .002). The ACL-R group with low voluntary activation
      (CAR < 0.95) had higher AMT than the control group (P = .02), whereas the ACL-R
      group with high voluntary activation (CAR >= 0.95) demonstrated higher H : M
      ratios than the control group (P = .05). CONCLUSIONS: The higher VM AMT in the
      injured limbs of ACL-R patients suggested that corticomotor deficits were present
      after surgery. Higher bilateral H : M ratios in ACL-R patients may be a strategy
      to reflexively increase excitability to maintain voluntary activation.

PMID- 25844856
TI  - A Refined Prediction Model for Core and Lower Extremity Sprains and Strains Among
      Collegiate Football Players.
AB  - CONTEXT: Researchers have identified high exposure to game conditions, low back
      dysfunction, and poor endurance of the core musculature as strong predictors for
      the occurrence of sprains and strains among collegiate football players.
      OBJECTIVE: To refine a previously developed injury-prediction model through
      analysis of 3 consecutive seasons of data. DESIGN: Cohort study. SETTING:
      National Collegiate Athletic Association Division I Football Championship
      Subdivision football program. PATIENTS OR OTHER PARTICIPANTS: For 3 consecutive
      years, all 152 team members (age = 19.7 +/- 1.5 years, height = 1.84 +/- 0.08 m,
      mass = 101.08 +/- 19.28 kg) presented for a mandatory physical examination on the
      day before initiation of preseason practice sessions. MAIN OUTCOME MEASURE(S):
      Associations between preseason measurements and the subsequent occurrence of a
      core or lower extremity sprain or strain were established for 256 player-seasons
      of data. We used receiver operating characteristic analysis to identify optimal
      cut points for dichotomous categorizations of cases as high risk or low risk.
      Both logistic regression and Cox regression analyses were used to identify a
      multivariable injury-prediction model with optimal discriminatory power. RESULTS:
      Exceptionally good discrimination between injured and uninjured cases was found
      for a 3-factor prediction model that included equal to or greater than 1 game as
      a starter, Oswestry Disability Index score equal to or greater than 4, and poor
      wall-sit-hold performance. The existence of at least 2 of the 3 risk factors
      demonstrated 56% sensitivity, 80% specificity, an odds ratio of 5.28 (90%
      confidence interval = 3.31, 8.44), and a hazard ratio of 2.97 (90% confidence
      interval = 2.14, 4.12). CONCLUSIONS: High exposure to game conditions was the
      dominant injury risk factor for collegiate football players, but a surprisingly
      mild degree of low back dysfunction and poor core-muscle endurance appeared to be
      important modifiable risk factors that should be identified and addressed before
      participation.

PMID- 25844857
TI  - Short-Wave Diathermy Pretreatment and Inflammatory Myokine Response After High
      Intensity Eccentric Exercise.
AB  - CONTEXT: Various modalities have been used to pretreat skeletal muscle to
      attenuate inflammation. OBJECTIVE: To determine the effects of short-wave
      diathermy (SWD) preheating treatment on inflammation and stress markers after
      eccentric exercise. DESIGN: Controlled laboratory study. SETTING: University
      laboratory setting. PATIENTS OR OTHER PARTICIPANTS: Fifteen male (age = 22 +/-
      4.9 years, height = 179.75 +/- 9.56 cm, mass = 82.22 +/- 12.67 kg) college-aged
      students. INTERVENTION(S): Seven participants were selected randomly to receive
      40 minutes of SWD heat treatment (HT), and 8 participants served as the control
      (CON) group and rested without SWD. Both groups completed 7 sets of 10
      repetitions of a high-intensity eccentric exercise protocol (EEP) at 120% of the
      1-repetition maximum (1-RM) leg extension. MAIN OUTCOME MEASURE(S): We biopsied
      muscles on days 1, 3 (24 hours post-EEP), and 4 (48 hours post-EEP) and collected
      blood samples on days 1, 2 (4 hours post-EEP), 3, and 4. We determined 1-RM on
      day 2 (24 hours post-SWD) and measured 1-RM on days 3 and 4. We analyzed the
      muscle samples for interleukin 6 (IL-6), tumor necrosis factor alpha, and heat
      shock protein 70 and the blood for serum creatine kinase. RESULTS: We found a
      group * time interaction for intramuscular IL-6 levels after SWD (F2,26 = 7.13, P
      = .003). The IL-6 decreased in HT (F1,6 = 17.8, P = .006), whereas CON showed no
      change (P > .05). We found a group * time interaction for tumor necrosis factor
      alpha levels (F2,26 = 3.71, P = .04), which increased in CON (F2,14 = 7.16, P =
      .007), but saw no changes for HT (P > .05). No group * time interactions were
      noted for 1-RM, heat shock protein 70, or creatine kinase (P > .05). CONCLUSIONS:
      The SWD preheating treatment provided a treatment effect for intramuscular
      inflammatory myokines induced through high-intensity eccentric exercise but did
      not affect other factors associated with intense exercise and inflammation.

PMID- 25844859
TI  - Biodegradation of carbofuran in soils within Nzoia River Basin, Kenya.
AB  - Carbofuran (2,3-dihydro-2,2-dimethylbenzofuran-7-yl methylcarbamate) has been
      used within the Nzoia River Basin (NRB), especially in Bunyala Rice Irrigation
      Schemes, in Kenya for the control of pests. In this study, the capacity of native
      bacteria to degrade carbofuran in soils from NRB was investigated. A gram
      positive, rod-shaped bacteria capable of degrading carbofuran was isolated
      through liquid cultures with carbofuran as the only carbon and nitrogen source.
      The isolate degraded 98% of 100-MUg mL(-1) carbofuran within 10 days with the
      formation of carbofuran phenol as the only detectable metabolite. The degradation
      of carbofuran was followed by measuring its residues in liquid cultures using
      high performance liquid chromatography (HPLC). Physical and morphological
      characteristics as well as molecular characterization confirmed the bacterial
      isolate to be a member of Bacillus species. The results indicate that this strain
      of Bacillus sp. could be considered as Bacillus cereus or Bacillus thuringiensis
      with a bootstrap value of 100% similar to the 16S rRNA gene sequences. The
      biodegradation capability of the native strains in this study indicates that they
      have great potential for application in bioremediation of carbofuran-contaminated
      soil sites.

PMID- 25844858
TI  - Add-On Treatment with Liraglutide Improves Glycemic Control in Patients with Type
      2 Diabetes on Metformin Therapy.
AB  - BACKGROUND: Liraglutide is a glucagon-like peptide-1 receptor analog recently
      approved for the treatment of type 2 diabetes mellitus (T2DM). We aimed to assess
      the efficacy and safety of liraglutide versus glimepiride, as adjunct treatments
      to metformin, in achieving glycemic control in Italian patients with T2DM
      uncontrolled by metformin alone. SUBJECTS AND METHODS: One hundred seventy-nine
      diabetes patients treated with metformin plus liraglutide (1.8 mg) or glimepiride
      (4 mg) were retrospectively assessed at baseline, during, and after 18 months of
      continuous therapy. RESULTS: Treatment with liraglutide resulted in mean
      decreases in hemoglobin A1c (HbA1c) of -1.4%, when compared with glimepiride (
      0.4%) (P < 0.001), and was followed by a significant reduction (P < 0.001) in
      fasting plasma glucose. Variations in HbA1c occurred independently from weight
      loss, which was significantly reduced (P < 0.001) in liraglutide-treated
      patients. The percentage of subjects reaching HbA1c levels below 7% or <= 6.5%
      was significantly different between the two treated groups (P < 0.001). Treatment
      with liraglutide reduced waist circumference (WC) (P < 0.001) and decreased both
      systolic and diastolic blood pressure (BP) (P < 0.001). It is interesting that
      the study also showed the impact of female gender in predicting a better glycemic
      response to liraglutide (P = 0.028). CONCLUSIONS: Liraglutide was more effective
      than glimepiride in reducing HbA1c levels in treated patients with T2DM. This was
      evident in both genders, but particularly in women. Furthermore, liraglutide
      reduced body weight, WC, and BP, which are critical risk factors for
      cardiovascular disease.

PMID- 25844860
TI  - Pesticides residues in the Prochilodus costatus (Valenciennes, 1850) fish caught
      in the Sao Francisco River, Brazil.
AB  - The objective of this study was to determine the levels of pesticides in the fish
      Prochilodus costatus caught in Sao Francisco River, one of most important rivers
      in Brazil. Thirty-six fish were captured in three different areas, and samples of
      the dorsal muscle and pooled viscera were collected for toxicological analysis.
      We evaluated the presence of 150 different classes of insecticides, fungicides,
      herbicides and acaricides by multiresidue analysis technique using liquid
      chromatography-tandem mass spectrometry (LC-MS/MS), with the limit of detection
      of 5 ppb. In this study, organophosphorus and carbamate pesticides were detected
      at the highest levels in the caught fish. Among the 41 organophosphorus
      pesticides surveyed, nine types were detected (chlorpyrifos, diazinon,
      dichlorvos, disulfoton, ethion, etrimfos, phosalone, phosmet and pyrazophos) in
      the muscle, viscera pool, or both in 22 (61.1%) fish. Sampled tissues of 20
      (55.6%) fish exhibited at least one of the eight evaluated carbamate pesticides
      and their metabolites: aldicarb, aldicarb sulfoxide, carbaryl, carbofuran,
      carbosulfan, furathiocarb, methomyl and propoxur. Fungicides (carbendazim,
      benalaxyl, kresoxim-methyl, trifloxystrobin, pyraclostrobin and its metabolite BF
      500 pyraclostrobin), herbicides (pyridate and fluasifop p-butyl), acaricide
      (propargite) and pyrethroid (flumethrin) were also detected. In conclusion, P.
      costatus fish caught in the Sao Francisco River contained residues of 17
      different pesticides, in both muscles and the viscera pool, indicating heavy
      environmental contamination by pesticides in the study area.

PMID- 25844861
TI  - Acute toxicity and ecotoxicological risk assessment of rice pesticides to
      Lithobates catesbeianus tadpoles.
AB  - The objective of this study was to determine the acute toxicity of some
      pesticides used in irrigated rice farming to Lithobates catesbeianus tadpoles.
      The LC 50-96h for commercial formulations containing bentazon, penoxsulam,
      vegetable oil, permethrin and carbofuran, separately and their mixtures, were
      determined at the proportions commonly used in the field. The limits of risk
      concentrations of these products for the studied species were also established.
      The LC 50-96h for tadpoles was 4,530 mg L(-1) for bentazon; 7.52 mg L(-1) for
      penoxsulam + 145.66 mg L(-1) of vegetable oil; 81.57 mg L(-1) for vegetable oil;
      0.10 mg L(-1) for permethrin; 29.90 mg L(-1) for carbofuran (active ingredients),
      and 38.79 times the dose used in the field for the mixture of these products. The
      environmental risk was determined only for permethrin, and care should be taken
      when using the vegetable oil.

PMID- 25844863
TI  - Resistance and virulence factors of Escherichia coli isolated from chicken.
AB  - Chicken meat has become an important part of the human diet and besides
      contamination by pathogenic Escherichia coli there is a risk of antibiotic
      resistance spreading via the food chain. The purpose of this study was to examine
      the prevalence of resistance against eight antibiotics and the presence of 14
      virulence factors among 75 Escherichia coli strains isolated from chicken meat in
      the Czech Republic after classification into phylogenetic groups by the multiplex
      PCR method. More than half of strains belonged to A phylogroup, next frequently
      represented was B1 phylogroup, which suggests the commensal strains. The other
      strains were classified into phylogroups B2 and D, which had more virulence
      factors. Almost half of all E. coli strains were resistant to at least one of
      eight-tested antibiotics. A multidrug resistance was observed in 13% of strains.
      The most prevalent virulence genes were iucD, iss and tsh. None of genes encoding
      toxins was detected. Most of E. coli strains isolated from chicken meat can be
      considered as nonpathogenic on the basis of analysis of virulence factors,
      antibiotic resistance and phylogroups assignment. It can provide a useful tool
      for prediction of a potential risk from food contaminated by E. coli. 

PMID- 25844862
TI  - Assessment of a potential preventive ability of amygdalin in mycotoxin-induced
      ovarian toxicity.
AB  - The possible effects of a natural substance amygdalin and its combination with
      the mycotoxin deoxynivalenol (DON) on the steroid hormone secretion (progesterone
      and 17-beta-estradiol) by porcine ovarian granulosa cells (GCs) were examined in
      this in vitro study. Ovarian GCs were incubated without (control group) and with
      amygdalin (1, 10, 100, 1,000 and 10,000 MUg mL(1)), or its combination with DON
      (1 MUg mL(1)) for 24 h. The release of steroid hormones was determined by ELISA.
      The progesterone secretion by porcine ovarian GCs was not affected by amygdalin
      in comparison to the control. However, the highest amygdalin dose (10,000 MUg
      mL(1)) caused a significant stimulation of the 17-beta-estradiol release. A
      combination of amygdalin with DON significantly (P < 0.05) increased the
      progesterone release at all concentrations. Similarly, a stimulatory effect of
      amygdalin co-administered with DON was detected with respect to the 17-beta
      estradiol secretion at the highest dose (10,000 MUg mL(1)) of amygdalin and 1 MUg
      mL(1) of DON. Noticeable differences between the effects of amygdalin alone and
      its combination with DON on the progesterone release were detected. In contrast,
      no differences between the stimulatory effects of amygdalin and its combination
      with DON on the 17-beta-estradiol synthesis by porcine GCs were observed.
      Findings from this in vitro study did not confirm the expected protective effect
      of amygdalin on mycotoxin induced reprotoxicity. Our results indicate that the
      stimulatory effect of amygdalin combined with DON on the progesterone release was
      clearly caused by the DON addition, not by the presence amygdalin per se. On the
      other hand, the stimulation of 17-beta-estradiol production was solely caused by
      the presence of amygdalin addition. These findings suggest a possible involvement
      of both natural substances into the processes of steroidogenesis and appear to be
      endocrine modulators of porcine ovaries.

PMID- 25844864
TI  - Specificity of Salmonella Typhimurium strain (ATCC 14028) growth responses to
      Salmonella serovar-generated spent media.
AB  - Salmonella enterica is one of the most prevalent pathogens responsible for
      foodborne illness worldwide. Numerous Salmonella serovars have been associated
      with the consumption of a variety of products, and limiting food-borne illness
      due to Salmonella serovars is a continuing problem for food producers and public
      health. The emergence and prevalence of Salmonella serovars has been studied but
      the predominant serovars have varied somewhat over the years. The aims of this
      research were to compare the aerobic growth responses of selected predominant
      foodborne Salmonella serovars, and evaluate how the spent media from different
      serovars affects the growth of a well-characterized Salmonella Typhimurium
      strain. Growth responses were similar for most strains in spent media except for
      S. Typhimurium (ATCC 14028), which exhibited a decrease in growth in the presence
      of Salmonella Heidelberg (ARI-14) spent media. This research will provide a
      better understanding of the growth differences among several Salmonella serovars
      in nutrient limited spent media. 

PMID- 25844865
TI  - Assessment of a composting process for the treatment of beef cattle manure.
AB  - The intensive breeding of beef cattle in Juncosa de les Garrigues (Catalonia,
      Spain) leads to the production of a large volume of manure that needs appropriate
      management. Land application in the area at agronomic rates is not enough to
      ensure good management practices, making necessary extended on-farm storage and
      the export of part of the production to long distances. In this context, the
      implementation of a collective treatment based on composting could help in
      enhancing the handling of manure. We assessed a full-scale composting process
      based on turned windrows (W), and involving treatment of beef cattle manure (CM)
      alone (two typologies were considered according to carbon-to-nitrogen ratios of
      ~25 (CM1, W1) and ~14 (CM2, W2)), or mixed with bulking agent (CM2/BA, W3) and
      dewatered digested sewage sludge (CM2/BA/DDSS, W4). Composting significantly
      improved the transportability of nutrients (final volumes were 40-54% of the
      initial volume). Temperature >55 degrees C was reached in all the treatments but
      following different time patterns. Under the applied conditions of turning and
      rewetting, 14 weeks of processing did not ensure the production of stable, and
      mature, compost. Thus, only compost from W1 attained the maximum degree of
      stability as well as concentration of ammonium-N < 0.01% (with ammonium-N/nitrate
      N ratio of 0.2) and low phytotoxicity. However, high pH, salinity, and heavy
      metal contents (Cu and Zn) may limit its final use. Addition of BA was advised to
      be kept to minimum, whereas use of DDSS as a co-substrate was not recommended in
      agreement to the higher loss of N and levels of heavy metals in the final
      compost. 

PMID- 25844866
TI  - Elemental distribution and uptake by watercress (Nasturtium aquaticum) as a
      function of water quality.
AB  - Watercress (Nasturtium aquaticum), is an edible plant commonly found in Southern
      Africa, which grows both in terrestrial and aquatic environments. The elemental
      concentrations in the plant and surrounding water (growth solution) were
      investigated to determine the plants nutritional value and to establish impact of
      water quality on elemental uptake by the plant. The concentrations in the leaves,
      roots and water were analyzed at eight different sites along the east coast of
      KwaZulu-Natal, South Africa (30.0000 degrees  S, 25.0000 degrees  E). Elemental
      concentrations in the leaves/roots (MUg g(-1), dry mass) and water
      exchangeable/total (MUg L(-1)) at Verulam (situated in the northern part of
      KwaZulu-Natal) were: As (1.2/7.5 and 0.053/0.09), Ca (18272/26091 and
      0.336/7.15), Cd (0.9/0.8 and 0.004/0.01), Co (37.2/34 and 0/0), Cr (7/35 and
      0.003/0.03), Cu (3/19 and 0.016/0.16), Fe (528/4308 and 0.375/0.6), Mg (3444/1141
      and 6.4/7), Mn (110/667 and 0/0), Ni (20/63 and 0/0.01), Pb (16/17 and
      0.01/0.02), Se (28/11 and 0.003/0.01) and Zn (102/116 and 0.099/0.36). Elemental
      uptake was controlled by the plant but water quality did have an impact on
      uptake. Concentrations of metals in the leaves were in decreasing order of Ca >
      Mg > Fe > Mn > Zn > Cu > Cr > Ni > Pb > Se > Cd > As > Co. The watercress plant
      was found to be a rich source of essential elements especially Fe and Cr and
      contained low concentrations of the toxic metals investigated thereby making it
      safe for human consumption.

PMID- 25844868
TI  - Acute Physiological and Mechanical Responses During Resistance Exercise at the
      Lactate Threshold Intensity.
AB  - The purpose of this study was to examine acute metabolic, mechanical, and cardiac
      responses to half-squat (HS) resistance exercise performed at a workload
      corresponding to the lactate threshold (LT). Thirteen healthy subjects completed
      3 HS exercise tests separated by 48-hour rest periods: a maximal strength or 1
      repetition maximum (1RM) test, an incremental load test to establish the % 1RM at
      which the LT was reached, and a constant load test at the LT intensity. During
      the last test, metabolic, mechanical, and cardiac responses were monitored
      respectively through blood lactate concentrations, height (H), average power (AP)
      and peak power (PP) recorded in a countermovement jump test, and heart rate (HR).
      During the constant load test, lactate concentrations and HR remained stable
      whereas significant reductions were detected in H, AP, and PP (p <= 0.05). Only
      low correlation was observed between lactate concentrations and the H (r =
      0.028), AP (r = 0.072), and PP (r = 0.359) losses produced. Half-squat exercise
      at the LT elicits stable HR and blood lactate responses within a predominantly
      aerobic metabolism, although this exercise modality induces significant
      mechanical fatigue.

PMID- 25844867
TI  - Heart Rate-Based Prediction of Fixed Blood Lactate Thresholds in Professional
      Team-Sport Players.
AB  - The aim of this study was to investigate whether the speed associated with 90% of
      maximal heart rate (S90%HRmax) could predict speeds at fixed blood lactate
      concentrations of 3 mmol.L(-1) (S3mM) and 4 mmol.L(-1) (S4mM). Professional team
      sport players of futsal (n = 10), handball (n = 16), and basketball (n = 10)
      performed a 4-stage discontinuous progressive running test followed, if
      exhaustion was not previously achieved, by an additional maximal continuous
      incremental running test to attain maximal heart rate (HRmax). The individual
      S3mM, S4mM, and S90%HRmax were determined by linear interpolation. S3mM (11.6 +/-
      1.5 km.h(-1)) and S4mM (12.5 +/- 1.4 km.h(-1)) did not differ (p > 0.05) from
      S90%HRmax (12.0 +/- 1.2 km.h(-1)). Very large significant (p < 0.001)
      relationships were found between S90%HRmax and S3mM (r = 0.82; standard error of
      the estimates [SEE] = 0.87 km.h(-1)), as well as between S90%HRmax and S4mM (r =
      0.82; SEE = 0.87 km.h(-1)). S3mM and S4mM inversely correlated with %HRmax
      associated with running speeds of 10 and 12 km.h(-1) (r = 0.78-0.81; p < 0.001;
      SEE = 0.94-0.87 km.h(-1)). In conclusion, S3mM and S4mM can be accurately
      predicted by S90%HRmax in professional team-sport players.

PMID- 25844869
TI  - Effects of an Unstable Load on Force and Muscle Activation During a Parallel Back
      Squat.
AB  - Stability training has become commonplace in the strength and conditioning field.
      Although unstable surface training has been investigated, little is known
      regarding the efficacy of performing resistance exercises with an unstable load.
      The purpose of this study was to determine if performing a parallel back squat
      with an unstable load (weights suspended from the bar by an elastic band)
      produces greater ground reaction forces (GRFs) and muscle activation in the trunk
      and lower extremities than a stable condition (a normally loaded barbell).
      Fifteen resistance-trained males (age: 24.2 +/- 3.4 years, mass: 83.4 +/- 18.7
      kg) completed 10 repetitions of the back squat, with 60% of their 1 repetition
      maximum in both stable and unstable conditions. Peak vertical GRF and the
      integrated muscle activity of the rectus femoris, vastus lateralis, vastus
      medialis, biceps femoris, soleus, rectus abdominis, external oblique, and erector
      spinae muscles on the right side of the body were determined The unstable load
      resulted in a small (3.9%) but significant decrease in peak vertical GRF. The
      unstable load also produced greater muscle activation in the rectus abdominis,
      external oblique, and soleus. The findings of this study suggest that squatting
      with an unstable load will increase activation of the stabilizing musculature;
      and while force decrements were statistically significant, the decrease was so
      small it may not be relevant to practitioners.

PMID- 25844870
TI  - High-intensity light-emitting diode vs fluorescent tubes for intensive
      phototherapy in neonates.
AB  - BACKGROUND: Special blue fluorescent tubes are recommended by the American
      Academy of Pediatrics (AAP) as the most effective light source for lowering serum
      bilirubin. A high-intensity light-emitting diode ('super LED') could render
      intensive phototherapy more effective than the above conventional methods. This
      study compared the efficacy and safety of a high-intensity light-emitting diode
      bed vs conventional intensive phototherapy with triple fluorescent tube units as
      a rescue treatment for severe unconjugated neonatal hyperbilirubinaemia. METHOD:
      This was a randomised, prospective trial. Two hundred jaundiced neonates >= 35
      weeks gestation who met the criteria for intensive phototherapy as per AAP
      guidelines were randomly assigned to be treated either with triple fluorescent
      tube units (group 1, n = 100) or a super LED bed (group 2, n = 100). The outcome
      was the avoidance of exchange transfusion by successful control of
      hyperbilirubinaemia. RESULTS: Statistically significant higher success rates of
      intensive phototherapy were achieved among neonates treated with super LED (group
      2) than in those treated conventionally (group 1) (87% vs 64%, P = 0.003).
      Significantly higher 'bilirubin decline' rates were reported in both haemolytic
      and non-haemolytic subgroups treated with the super LED bed compared with a
      similar sub-population in the conventionally treated group. Comparable numbers of
      neonates in both groups developed rebound jaundice (8% vs 10% of groups 1 and 2,
      respectively). Side-effects were mild in both groups, but higher rates of
      hyperthermia (12% vs 0%, P = 0.03), dehydration (8% vs 2%, P = 0.26) and skin
      rash (39% vs 1%, P = 0.002) were reported in the fluorescent tubes-treated group
      compared with the LED group. CONCLUSIONS: Super LED is a safe rescue treatment
      for severe neonatal hyperbilirubinaemia, and its implementation may reduce the
      need for exchange transfusion.

PMID- 25844871
TI  - Alpha-synuclein levels in blood plasma decline with healthy aging.
AB  - There is unequivocal evidence that alpha-synuclein plays a pivotal
      pathophysiological role in neurodegenerative diseases, and in particular in
      synucleinopathies. These disorders present with a variable extent of cognitive
      impairment and alpha-synuclein is being explored as a biomarker in CSF, blood
      serum and plasma. Considering key events of aging that include proteostasis,
      alpha-synuclein may not only be useful as a marker for differential diagnosis but
      also for aging per se. To explore this hypothesis, we developed a highly specific
      ELISA to measure alpha-synuclein. In healthy males plasma alpha-synuclein levels
      correlated strongly with age, revealing much lower concentrations in older (avg.
      58.1 years) compared to younger (avg. 27.6 years) individuals. This difference
      between the age groups was enhanced after acidification of the plasmas
      (p<0.0001), possibly reflecting a decrease of alpha-synuclein-antibody complexes
      or chaperone activity in older individuals. Our results support the concept that
      alpha-synuclein homeostasis may be impaired early on, possibly due to disturbance
      of the proteostasis network, a key component of healthy aging. Thus, alpha
      synuclein may be a novel biomarker of aging, a factor that should be considered
      when analyzing its presence in biological specimens. 

PMID- 25844872
TI  - Correction: the suppression of WRKY44 by GIGANTEA-miR172 pathway is involved in
      drought response of Arabidopsis thaliana.

PMID- 25844874
TI  - A complementary processes account of the development of childhood amnesia and a
      personal past.
AB  - Personal-episodic or autobiographical memories are an important source of
      evidence for continuity of self over time. Numerous studies conducted with adults
      have revealed a relative paucity of personal-episodic or autobiographical
      memories of events from the first 3 to 4 years of life, with a seemingly gradual
      increase in the number of memories until approximately age 7 years, after which
      an adult distribution has been assumed. Historically, this so-called infantile
      amnesia or childhood amnesia has been attributed either to late development of
      personal-episodic or autobiographical memory (implying its absence in the early
      years of life) or to an emotional, cognitive, or linguistic event that renders
      early autobiographical memories inaccessible to later recollection. However,
      neither type of explanation alone can fully account for the shape of the
      distribution of autobiographical memories early in life. In contrast, the
      complementary processes account developed in this article acknowledges early,
      gradual development of the ability to form, retain, and later retrieve memories
      of personally relevant past events, as well as an accelerated rate of forgetting
      in childhood relative to adulthood. The adult distribution of memories is
      achieved as (a) the quality of memory traces increases, through addition of more,
      better elaborated, and more tightly integrated personal-episodic or
      autobiographical features; and (b) the vulnerability of mnemonic traces
      decreases, as a result of more efficient and effective neural, cognitive, and
      specifically mnemonic processes, thus slowing the rate of forgetting. The
      perspective brings order to an array of findings from the adult and developmental
      literatures.

PMID- 25844875
TI  - Informing cognitive abstractions through neuroimaging: the neural drift diffusion
      model.
AB  - Trial-to-trial fluctuations in an observer's state of mind have a direct
      influence on their behavior. However, characterizing an observer's state of mind
      is difficult to do with behavioral data alone, particularly on a single-trial
      basis. In this article, we extend a recently developed hierarchical Bayesian
      framework for integrating neurophysiological information into cognitive models.
      In so doing, we develop a novel extension of the well-studied drift diffusion
      model (DDM) that uses single-trial brain activity patterns to inform the
      behavioral model parameters. We first show through simulation how the model
      outperforms the traditional DDM in a prediction task with sparse data. We then
      fit the model to experimental data consisting of a speed-accuracy manipulation on
      a random dot motion task. We use our cognitive modeling approach to show how
      prestimulus brain activity can be used to simultaneously predict response
      accuracy and response time. We use our model to provide an explanation for how
      activity in a brain region affects the dynamics of the underlying decision
      process through mechanisms assumed by the model. Finally, we show that our model
      performs better than the traditional DDM through a cross-validation test. By
      combining accuracy, response time, and the blood oxygen level-dependent response
      into a unified model, the link between cognitive abstraction and neuroimaging can
      be better understood.

PMID- 25844876
TI  - Expanding the scope of memory search: Modeling intralist and interlist effects in
      free recall.
AB  - The human memory system is remarkable in its capacity to focus its search on
      items learned in a given context. This capacity can be so precise that many
      leading models of human memory assume that only those items learned in the
      context of a recently studied list compete for recall. We sought to extend the
      explanatory scope of these models to include not only intralist phenomena, such
      as primacy and recency effects, but also interlist phenomena such as proactive
      and retroactive interference. Building on retrieved temporal context models of
      memory search (e.g., Polyn, Norman, & Kahana, 2009), we present a substantially
      revised theory in which memory accumulates across multiple experimental lists,
      and temporal context is used both to focus retrieval on a target list, and to
      censor retrieved information when its match to the current context indicates that
      it was learned in a nontarget list. We show how the resulting model can
      simultaneously account for a wide range of intralist and interlist phenomena,
      including the pattern of prior-list intrusions observed in free recall, build-up
      of and release from proactive interference, and the ability to selectively target
      retrieval of items on specific prior lists (Jang & Huber, 2008; Shiffrin, 1970).
      In a new experiment, we verify that subjects' error monitoring processes are
      consistent with those predicted by the model.

PMID- 25844873
TI  - Robust speech perception: recognize the familiar, generalize to the similar, and
      adapt to the novel.
AB  - Successful speech perception requires that listeners map the acoustic signal to
      linguistic categories. These mappings are not only probabilistic, but change
      depending on the situation. For example, one talker's /p/ might be physically
      indistinguishable from another talker's /b/ (cf. lack of invariance). We
      characterize the computational problem posed by such a subjectively nonstationary
      world and propose that the speech perception system overcomes this challenge by
      (a) recognizing previously encountered situations, (b) generalizing to other
      situations based on previous similar experience, and (c) adapting to novel
      situations. We formalize this proposal in the ideal adapter framework: (a) to (c)
      can be understood as inference under uncertainty about the appropriate generative
      model for the current talker, thereby facilitating robust speech perception
      despite the lack of invariance. We focus on 2 critical aspects of the ideal
      adapter. First, in situations that clearly deviate from previous experience,
      listeners need to adapt. We develop a distributional (belief-updating) learning
      model of incremental adaptation. The model provides a good fit against known and
      novel phonetic adaptation data, including perceptual recalibration and selective
      adaptation. Second, robust speech recognition requires that listeners learn to
      represent the structured component of cross-situation variability in the speech
      signal. We discuss how these 2 aspects of the ideal adapter provide a unifying
      explanation for adaptation, talker-specificity, and generalization across talkers
      and groups of talkers (e.g., accents and dialects). The ideal adapter provides a
      guiding framework for future investigations into speech perception and
      adaptation, and more broadly language comprehension.

PMID- 25844877
TI  - Risk attitudes in a changing environment: An evolutionary model of the fourfold
      pattern of risk preferences.
AB  - A striking feature of human decision making is the fourfold pattern of risk
      attitudes, involving risk-averse behavior in situations of unlikely losses and
      likely gains, but risk-seeking behavior in response to likely losses and unlikely
      gains. Current theories to explain this pattern assume particular psychological
      processes to reproduce empirical observations, but do not address whether it is
      adaptive for the decision maker to respond to risk in this way. Here, drawing on
      insights from behavioral ecology, we build an evolutionary model of risk
      sensitive behavior, to investigate whether particular types of environmental
      conditions could favor a fourfold pattern of risk attitudes. We consider an
      individual foraging in a changing environment, where energy is needed to prevent
      starvation and build up reserves for reproduction. The outcome, in terms of
      reproductive value (a rigorous measure of evolutionary success), of a one-off
      choice between a risky and a safe gain, or between a risky and a safe loss,
      determines the risk-sensitive behavior we should expect to see in this
      environment. Our results show that the fourfold pattern of risk attitudes may be
      adaptive in an environment in which conditions vary stochastically but are
      autocorrelated in time. In such an environment the current options provide
      information about the likely environmental conditions in the future, which affect
      the optimal pattern of risk sensitivity. Our model predicts that risk preferences
      should be both path dependent and affected by the decision maker's current state.

PMID- 25844878
TI  - Slow down and remember to remember! A delay theory of prospective memory costs.
AB  - Event-based prospective memory (PM) requires a deferred action to be performed
      when a target event is encountered in the future. Individuals are often slower to
      perform a concurrent ongoing task when they have PM task requirements relative to
      performing the ongoing task in isolation. Theories differ in their detailed
      interpretations of this PM cost, but all assume that the PM task shares limited
      capacity resources with the ongoing task. In what was interpreted as support of
      this core assumption, diffusion model fits reported by Boywitt and Rummel (2012)
      and Horn, Bayen, and Smith (2011) indicated that PM demands reduced the rate of
      accumulation of evidence about ongoing task choices. We revaluate this support by
      fitting both the diffusion and linear ballistic accumulator (Brown & Heathcote,
      2008) models to these same data sets and 2 new data sets better suited to model
      fitting. There was little effect of PM demands on evidence accumulation rates,
      but PM demands consistently increased the evidence required for ongoing task
      response selection (response thresholds). A further analysis of data reported by
      Lourenco, White, and Maylor (2013) found that participants differentially
      adjusted their response thresholds to slow responses associated with stimuli
      potentially containing PM targets. These findings are consistent with a delay
      theory account of costs, which contends that individuals slow ongoing task
      responses to allow more time for PM response selection to occur. Our results call
      for a fundamental reevaluation of current capacity-sharing theories of PM cost
      that until now have dominated the PM literature.

PMID- 25844879
TI  - Concerns about the Australian Institute of Health and Welfare's information on
      capital investment for healthcare.

PMID- 25844880
TI  - Two-photon fluorescent probes for biological Mg(2+) detection based on 7
      substituted coumarin.
AB  - Two novel water-soluble coumarin-based compounds (OC7, NC7) were designed and
      synthesized as two-photon fluorescent probes for biological Mg(2+) detection. The
      compounds feature a beta-keto acid as a high selective binding site for Mg(2+)
      and the coumarin framework as the two-photon fluorophore. OC7 and NC7 show
      significant "off-on" detecting signals (9.05-fold and 23.8-fold fluorescence
      enhancement) and lower detection limits compared with previous reported two
      photon fluorescent probes for Mg(2+). Moreover, OC7-Mg(2+) and NC7-Mg(2+) exhibit
      large two-photon absorption cross sections (340 and 615 GM) at the near-infrared
      wavelengths (740 and 860 nm), which indicates that the probes are very suitable
      for detection of Mg(2+) in vivo. Both OC7 and NC7 are pH-insensitive and of low
      cytotoxicity and can be applied to image intracellular Mg(2+) under two-photon
      microscopy (TPM). Our results provide a strategy to modify the coumarin
      fluorophore to get better two-photon fluorescent properties. And the results also
      suggest that electronic density of beta-keto acid plays a very important role in
      the recognition of Mg(2+). 

PMID- 25844881
TI  - A patient with a biventricular pacemaker presenting with chest pain.

PMID- 25844882
TI  - Effect of Moderate to Vigorous Physical Activity on All-Cause Mortality in Middle
      aged and Older Australians.
AB  - IMPORTANCE: Few studies have examined how different proportions of moderate and
      vigorous physical activity affect health outcomes. OBJECTIVE: To examine whether
      the proportion of total moderate to vigorous activity (MVPA) that is achieved
      through vigorous activity is associated with all-cause mortality independently of
      the total amount of MVPA. DESIGN, SETTING, AND PARTICIPANTS: We performed a
      prospective cohort study with activity data linked to all-cause mortality data
      from February 1, 2006, through June 15, 2014, in 204,542 adults aged 45 through
      75 years from the 45 and Up population-based cohort study from New South Wales,
      Australia (mean [SD] follow-up, 6.52 [1.23] years). Associations between
      different contributions of vigorous activity to total MVPA and mortality were
      examined using Cox proportional hazards models, adjusted for total MVPA and
      sociodemographic and health covariates. EXPOSURES: Different proportions of total
      MVPA as vigorous activity. Physical activity was measured with the Active
      Australia Survey. MAIN OUTCOMES AND MEASURES: All-cause mortality during the
      follow-up period. RESULTS: During 1,444,927 person-years of follow-up, 7435
      deaths were registered. Compared with those who reported no MVPA (crude death
      rate, 8.34%), the adjusted hazard ratios for all-cause mortality were 0.66 (95%
      CI, 0.61-0.71; crude death rate, 4.81%), 0.53 (95% CI, 0.48-0.57; crude death
      rate, 3.17%), and 0.46 (95% CI, 0.43-0.49; crude death rate, 2.64%) for reporting
      10 through 149, 150 through 299, and 300 min/wk or more of activity,
      respectively. Among those who reported any MVPA, the proportion of vigorous
      activity revealed an inverse dose-response relationship with all-cause mortality:
      compared with those reporting no vigorous activity (crude death rate, 3.84%) the
      fully adjusted hazard ratio was 0.91 (95% CI, 0.84-0.98; crude death rate, 2.35%)
      in those who reported some vigorous activity (but <30% of total activity) and
      0.87 (95% CI, 0.81-0.93; crude death rate, 2.08%) among those who reported 30% or
      more of activity as vigorous. These associations were consistent in men and
      women, across categories of body mass index and volume of MVPA, and in those with
      and without existing cardiovascular disease or diabetes mellitus. CONCLUSIONS AND
      RELEVANCE: Among people reporting any activity, there was an inverse dose
      response relationship between proportion of vigorous activity and mortality. Our
      findings suggest that vigorous activities should be endorsed in clinical and
      public health activity guidelines to maximize the population benefits of physical
      activity.

PMID- 25844883
TI  - The Human Alzheimer Disease Project: A New Call to Arms.

PMID- 25844884
TI  - Moving to high-value care: more thoughtful use of cardiopulmonary resuscitation.

PMID- 25844886
TI  - Using physical activity to gain the most public health bang for the buck.

PMID- 25844887
TI  - Temperature sensitivity of nanochannel electrical conductance.
AB  - Electrical measurement is a widely used technique for the characterization of
      nanofluidic devices. The electrical conductivity of electrolytes is known to be
      dependent on temperature. However, the similarity of the temperature sensitivity
      of the electrical conductivity for bulk and nanochannels has not been validated.
      In this work, we present the results from experimental measurements as well as
      analytical modeling that show the significant difference between bulk and
      nanoscale. The temperature sensitivity of the electrical conductance of
      nanochannel is higher at low ionic concentration where the nanofluidic transport
      is governed by the electrostatic effects from the wall. Neglecting this effect
      can result in significant errors for high temperature measurements. Additionally,
      the temperature sensitivity of the nanochannel conductance allows to measure the
      enthalpy change of surface reactions at low ionic concentrations. 

PMID- 25844888
TI  - Electroconvulsive therapy for obsessive-compulsive disorder: a systematic review.
AB  - OBJECTIVE: Surgical therapies for treatment-refractory obsessive-compulsive
      disorder (OCD), such as deep brain stimulation or psychosurgery, remain
      unattainable for many patients. Despite the long-held view that electroconvulsive
      therapy (ECT) is an ineffective treatment for OCD, there is no systematic review
      to support or refute this claim, which is the basis of the current review. DATA
      SOURCES: A systematic search of MEDLINE, Web of Science, Scopus, and LILACS
      databases was conducted on December 22, 2013, using the terms obsessive
      compulsive disorder and electroconvulsive therapy. Reference lists, specific
      journals, and clinical trial registries were also scrutinized. No date or
      language limitation was imposed on the search. STUDY SELECTION: After irrelevant
      and redundant records from the 500 identified titles were excluded, the 50
      articles reporting the acute treatment effects of ECT in OCD and related
      constructs (involving a total of 279 patients) were analyzed for this study. DATA
      EXTRACTION: The relevant sociodemographic, clinical, and outcome data of
      individual cases were extracted. Data from individual cases were used to compare
      the characteristics of responders versus nonresponders to ECT. RESULTS: Most
      selected records were case reports/series; there were no randomized controlled
      trials. A positive response was reported in 60.4% of the 265 cases in which
      individual responses to ECT were available. ECT responders exhibited a
      significantly later onset of OCD symptoms (P = .003), were more frequently
      nondepressed (P = .009), more commonly reported being treated with ECT for severe
      OCD (P = .01), and received a fewer number of ECT sessions (P = .03). ECT
      responders were also less frequently previously treated with adequate trials of
      serotonin reuptake inhibitors (P = .05) and cognitive-behavioral therapy (P =
      .005). CONCLUSIONS: Although 60% of the reported cases reviewed exhibited some
      form of a positive response to ECT, it cannot be stated that this provides
      evidence that ECT is indeed effective for OCD.

PMID- 25844889
TI  - Interaction Studies of Resolvin E1 Analog (RX-10045) with Efflux Transporters.
AB  - PURPOSE: Screening interactions of a resolvin E1 analog (RX-10045) with efflux
      transporters (P-glycoprotein [P-gp], multidrug resistance-associated protein
      [MRP2], and breast cancer-resistant protein [BCRP]). METHODS: Madin-Darby canine
      kidney cells transfected with P-gp, MRP2, and BCRP genes were selected for this
      study. [3H]-Digoxin, [3H]-vinblastine and [3H]-abacavir were selected as model
      substrates for P-gp, MRP2, and BCRP. Uptake and permeability studies across cell
      monolayer in both apical to basal (AP-BL) and BL-AP of these substrates were
      conducted in the presence of specific efflux pump inhibitors and RX-10045. Cell
      viability studies were conducted with increasing concentrations of RX-10045.
      RESULTS: Uptake studies showed a higher accumulation in the presence of
      inhibitors (GF120918 and ketoconazole for P-gp; MK571 for MRP2; and beta
      estradiol for BCRP) as well as RX-10045. Similarly, dose-dependent inhibition
      studies demonstrated higher accumulation of various substrates ([3H]-digoxin,
      [3H]-vinblastine, and [3H]-abacavir) in the presence of RX-10045. IC50 values of
      dose-dependent inhibition of RX-10045 for P-gp, MRP2, and BCRP were 239+/-11.2,
      291+/-79.2, and 300+/-42 MUM, respectively. Cell viability assay indicated no
      apparent toxicity up to 350 MUM concentration. Enhanced permeability for model
      substrates was observed in the presence of RX-10045. Uptake studies in human
      corneal epithelial cells suggest that RX-10045 is a strong inhibitor of organic
      cation transporter-1 (OCT-1). CONCLUSIONS: In summary, the resolvin analog (RX
      10045) was identified as a substrate/inhibitor for efflux transporters (MRP2 and
      BCRP). Also, RX-10045 appears to be a strong inhibitor/substrate of OCT-1. Novel
      formulation strategies such as nanoparticles, nanomicelles, and liposomes for
      circumventing efflux barriers and delivering higher drug concentrations leading
      to a higher therapeutic efficacy may be employed.

PMID- 25844890
TI  - Molecular tweezers inhibit islet amyloid polypeptide assembly and toxicity by a
      new mechanism.
AB  - In type-2 diabetes (T2D), islet amyloid polypeptide (IAPP) self-associates into
      toxic assemblies causing islet beta-cell death. Therefore, preventing IAPP
      toxicity is a promising therapeutic strategy for T2D. The molecular tweezer CLR01
      is a supramolecular tool for selective complexation of K residues in
      (poly)peptides. Surprisingly, it inhibits IAPP aggregation at substoichiometric
      concentrations even though IAPP has only one K residue at position 1, whereas
      efficient inhibition of IAPP toxicity requires excess CLR01. The basis for this
      peculiar behavior is not clear. Here, a combination of biochemical, biophysical,
      spectroscopic, and computational methods reveals a detailed mechanistic picture
      of the unique dual inhibition mechanism for CLR01. At low concentrations, CLR01
      binds to K1, presumably nucleating nonamyloidogenic, yet toxic, structures,
      whereas excess CLR01 binds also to R11, leading to nontoxic structures.
      Encouragingly, the CLR01 concentrations needed for inhibition of IAPP toxicity
      are safe in vivo, supporting its development toward disease-modifying therapy for
      T2D. 

PMID- 25844891
TI  - Effects of combining rapamycin and resveratrol on apoptosis and growth of TSC2
      deficient xenograft tumors.
AB  - Lymphangioleiomyomatosis (LAM) is a rare neoplastic metastatic disease affecting
      women of childbearing age. LAM is caused by hyperactivation of the mechanistic
      target of rapamycin complex 1 (mTORC1) as a consequence of tuberous sclerosis
      complex (TSC) 1/2 inactivation. Clinically, LAM results in cystic lung
      destruction. mTORC1 inhibition using rapamycin analogs (rapalogs) is partially
      effective in reducing disease progression and improving lung function. However,
      cessation of treatment results in continued progression of the disease. In the
      present study, we investigated the effectiveness of the combination of rapamycin
      treatment with resveratrol, an autophagy inhibitor, in the TSC2-null xenograft
      tumor model. We determined that this combination inhibits phosphatidylinositol
      4,5-bisphosphate 3-kinase PI3K/Akt/mTORC1 signaling and activates apoptosis.
      Therefore, the combination of rapamycin and resveratrol may be an effective
      clinical strategy for treatment of LAM and other diseases with mTORC1
      hyperactivation. 

PMID- 25844892
TI  - Association of definition of acute kidney injury by cystatin C rise with
      biomarkers and clinical outcomes in children undergoing cardiac surgery.
AB  - IMPORTANCE: Research has identified improved biomarkers of acute kidney injury
      (AKI). Cystatin C (CysC) is a better glomerular filtration rate marker than serum
      creatinine (SCr) and may improve AKI definition. OBJECTIVE: To determine if
      defining clinical AKI by increases in CysC vs SCr alters associations with
      biomarkers and clinical outcomes. DESIGN, SETTING, AND PARTICIPANTS: Three-center
      prospective cohort study of intensive care units in New Haven, Connecticut,
      Cincinnati, Ohio, and Montreal, Quebec, Canada. Participants were 287 patients 18
      years or younger without preoperative AKI or end-stage renal disease who were
      undergoing cardiac surgery. The study dates were July 1, 2007, through December
      31, 2009. EXPOSURES: For biomarker vs clinical AKI associations, the exposures
      were first postoperative (0-6 hours after surgery) urine interleukin 18,
      neutrophil gelatinase-associated lipocalin, kidney injury molecule 1, and liver
      fatty acid-binding protein. For clinical AKI outcome associations, the exposure
      was Kidney Disease: Improving Global Outcomes AKI definition (based on SCr or
      CysC). MAIN OUTCOMES AND MEASURES: Clinical AKI, length of stay, and length of
      mechanical ventilation. We determined areas under the receiver operating
      characteristic curve and odds ratios for first postoperative biomarkers to
      predict AKI. RESULTS: The SCr-defined vs CysC-defined AKI incidence differed
      substantially (43.6% vs 20.6%). Percentage agreement was 71% (kappa = 0.38);
      stage 2 or worse AKI percentage agreement was 95%. Interleukin 18 and kidney
      injury molecule 1 discriminated for CysC-defined AKI better than for SCr-defined
      AKI. For interleukin 18 and kidney injury molecule 1, the areas under the
      receiver operating characteristic curve were 0.74 and 0.65, respectively, for
      CysC-defined AKI, and 0.66 and 0.58, respectively, for SCr-defined AKI. Fifth (vs
      first) quintile concentrations of both biomarkers were more strongly associated
      with CysC-defined AKI. For interleukin 18 and kidney injury molecule 1, the odds
      ratios were 16.19 (95% CI, 3.55-73.93) and 6.93 (95% CI, 1.88-25.59),
      respectively, for CysC-defined AKI vs 6.60 (95% CI, 2.76-15.76) and 2.04 (95% CI,
      0.94-4.38), respectively, for SCr-defined AKI. Neutrophil gelatinase-associated
      lipocalin and liver fatty acid-binding protein associations with both definitions
      were similar. The CysC definitions and SCr definitions were similarly associated
      with clinical outcomes of resource use. CONCLUSIONS AND RELEVANCE: Compared with
      the SCr-based definition, the CysC-based definition is more strongly associated
      with urine interleukin 18 and kidney injury molecule 1 in children undergoing
      cardiac surgery. Consideration should be made for defining AKI based on CysC in
      clinical care and future studies.

PMID- 25844893
TI  - Catalytic mesoporous Janus nanomotors for active cargo delivery.
AB  - We report on the synergy between catalytic propulsion and mesoporous silica
      nanoparticles (MSNPs) for the design of Janus nanomotors as active cargo delivery
      systems with sizes <100 nm (40, 65, and 90 nm). The Janus asymmetry of the
      nanomotors is given by electron beam (e-beam) deposition of a very thin platinum
      (2 nm) layer on MSNPs. The chemically powered Janus nanomotors present active
      diffusion at low H2O2 fuel concentration (i.e., <3 wt %). Their apparent
      diffusion coefficient is enhanced up to 100% compared to their Brownian motion.
      Due to their mesoporous architecture and small dimensions, they can load cargo
      molecules in large quantity and serve as active nanocarriers for directed cargo
      delivery on a chip. 

PMID- 25844894
TI  - Triangular gold nanoplate growth by oriented attachment of Au seeds generated by
      strong field laser reduction.
AB  - The synthesis of surfactant-free Au nanoplates is desirable for the development
      of biocompatible therapeutics/diagnostics. Rapid Delta-function energy deposition
      by irradiation of aqueous KAuCl4 solution with a 5 s burst of intense shaped
      laser pulses, followed by slow addition of H2O2, results in selective formation
      of nanoplates with no additional reagents. The primary mechanism of nanoplate
      formation is found to be oriented attachment of the spherical seeds, which self
      recrystallize to form crystalline Au nanoplates. 

PMID- 25844896
TI  - Self-Assembly of PS-b-PDMS on a Tunable PDMS Template with Nanoscale Channels and
      Enhanced Anisotropic Wetting.
AB  - In this article, we systematically studied the self-assembly of poly(styrene
      block-dimethylsiloxane) (PS-b-PDMS) on a poly(dimethylsiloxane) (PDMS) substrate
      with nanoscale channels. The channeled PDMS substrate was achieved by a simple
      replica molding method. To decrease the effect that the subsequent solvent
      treatments had in distorting the soft PDMS substrate, a simple UV/O3 treatment
      was provided before the self-assembly, resulting in a relatively stable, harder
      and hydrophilic silicon oxide (SiO2) layer on the channeled PDMS surface.
      Ultimately, the isotropic SiO2 nanopatterns with spherical and long cylindrical
      morphologies were successfully fabricated by the self-assembly of two kinds of PS
      b-PDMS on the PDMS substrate with nanoscale channels, respectively. In
      particular, we demonstrated that the introduction of isotropic SiO2 patterns is
      an effective approach to greatly enhance anisotropic wetting rather than that of
      the anisotropic structure with channels. 

PMID- 25844895
TI  - Discovery of tricyclic indoles that potently inhibit Mcl-1 using fragment-based
      methods and structure-based design.
AB  - Myeloid cell leukemia-1 (Mcl-1) is an antiapoptotic member of the Bcl-2 family of
      proteins that is overexpressed and amplified in many cancers. Overexpression of
      Mcl-1 allows cancer cells to evade apoptosis and contributes to the resistance of
      cancer cells to be effectively treated with various chemotherapies. From an NMR
      based screen of a large fragment library, several distinct chemical scaffolds
      that bind to Mcl-1 were discovered. Here, we describe the discovery of potent
      tricyclic 2-indole carboxylic acid inhibitors that exhibit single digit nanomolar
      binding affinity to Mcl-1 and greater than 1700-fold selectivity over Bcl-xL and
      greater than 100-fold selectivity over Bcl-2. X-ray structures of these compounds
      when complexed to Mcl-1 provide detailed information on how these small-molecules
      bind to the target, which was used to guide compound optimization. 

PMID- 25844897
TI  - Quantification of mutant huntingtin protein in cerebrospinal fluid from
      Huntington's disease patients.
AB  - BACKGROUND: Quantification of disease-associated proteins in the cerebrospinal
      fluid (CSF) has been critical for the study and treatment of several
      neurodegenerative disorders; however, mutant huntingtin protein (mHTT), the cause
      of Huntington's disease (HD), is at very low levels in CSF and, to our knowledge,
      has never been measured previously. METHODS: We developed an ultrasensitive
      single-molecule counting (SMC) mHTT immunoassay that was used to quantify mHTT
      levels in CSF samples from individuals bearing the HD mutation and from control
      individuals in 2 independent cohorts. RESULTS: This SMC mHTT immunoassay
      demonstrated high specificity for mHTT, high sensitivity with a femtomolar
      detection threshold, and a broad dynamic range. Analysis of the CSF samples
      showed that mHTT was undetectable in CSF from all controls but quantifiable in
      nearly all mutation carriers. The mHTT concentration in CSF was approximately 3
      fold higher in patients with manifest HD than in premanifest mutation carriers.
      Moreover, mHTT levels increased as the disease progressed and were associated
      with 5-year onset probability. The mHTT concentration independently predicted
      cognitive and motor dysfunction. Furthermore, the level of mHTT was associated
      with the concentrations of tau and neurofilament light chain in the CSF,
      suggesting a neuronal origin for the detected mHTT. CONCLUSIONS: We have
      demonstrated that mHTT can be quantified in CSF from HD patients using the
      described SMC mHTT immunoassay. Moreover, the level of mHTT detected is
      associated with proximity to disease onset and diminished cognitive and motor
      function. The ability to quantify CSF mHTT will facilitate the study of HD, and
      mHTT quantification could potentially serve as a biomarker for the development
      and testing of experimental mHTT-lowering therapies for HD. TRIAL REGISTRATION:
      Not applicable. FUNDING: CHDI Foundation Inc.; Medical Research Council (MRC) UK;
      National Institutes for Health Research (NIHR); Rosetrees Trust; Swedish Research
      Council; and Knut and Alice Wallenberg Foundation.

PMID- 25844898
TI  - Sec63 and Xbp1 regulate IRE1alpha activity and polycystic disease severity.
AB  - The HSP40 cochaperone SEC63 is associated with the SEC61 translocon complex in
      the ER. Mutations in the gene encoding SEC63 cause polycystic liver disease in
      humans; however, it is not clear how altered SEC63 influences disease
      manifestations. In mice, loss of SEC63 induces cyst formation both in liver and
      kidney as the result of reduced polycystin-1 (PC1). Here we report that
      inactivation of SEC63 induces an unfolded protein response (UPR) pathway that is
      protective against cyst formation. Specifically, using murine genetic models, we
      determined that SEC63 deficiency selectively activates the IRE1alpha-XBP1 branch
      of UPR and that SEC63 exists in a complex with PC1. Concomitant inactivation of
      both SEC63 and XBP1 exacerbated the polycystic kidney phenotype in mice by
      markedly suppressing cleavage at the G protein-coupled receptor proteolysis site
      (GPS) in PC1. Enforced expression of spliced XBP1 (XBP1s) enhanced GPS cleavage
      of PC1 in SEC63-deficient cells, and XBP1 overexpression in vivo ameliorated
      cystic disease in a murine model with reduced PC1 function that is unrelated to
      SEC63 inactivation. Collectively, the findings show that SEC63 function regulates
      IRE1alpha/XBP1 activation, SEC63 and XBP1 are required for GPS cleavage and
      maturation of PC1, and activation of XBP1 can protect against polycystic disease
      in the setting of impaired biogenesis of PC1. 

PMID- 25844899
TI  - Calcium release channel RyR2 regulates insulin release and glucose homeostasis.
AB  - The type 2 ryanodine receptor (RyR2) is a Ca2+ release channel on the endoplasmic
      reticulum (ER) of several types of cells, including cardiomyocytes and pancreatic
      beta cells. In cardiomyocytes, RyR2-dependent Ca2+ release is critical for
      excitation-contraction coupling; however, a functional role for RyR2 in beta cell
      insulin secretion and diabetes mellitus remains controversial. Here, we took
      advantage of rare RyR2 mutations that were identified in patients with a genetic
      form of exercise-induced sudden death (catecholaminergic polymorphic ventricular
      tachycardia [CPVT]). As these mutations result in a "leaky" RyR2 channel, we
      exploited them to assess RyR2 channel function in beta cell dynamics. We
      discovered that CPVT patients with mutant leaky RyR2 present with glucose
      intolerance, which was heretofore unappreciated. In mice, transgenic expression
      of CPVT-associated RyR2 resulted in impaired glucose homeostasis, and an in-depth
      evaluation of pancreatic islets and beta cells from these animals revealed
      intracellular Ca2+ leak via oxidized and nitrosylated RyR2 channels, activated ER
      stress response, mitochondrial dysfunction, and decreased fuel-stimulated insulin
      release. Additionally, we verified the effects of the pharmacological inhibition
      of intracellular Ca2+ leak in CPVT-associated RyR2-expressing mice, in human
      islets from diabetic patients, and in an established murine model of type 2
      diabetes mellitus. Taken together, our data indicate that RyR2 channels play a
      crucial role in the regulation of insulin secretion and glucose homeostasis. 

PMID- 25844900
TI  - An epigenetically distinct breast cancer cell subpopulation promotes collective
      invasion.
AB  - Tumor cells can engage in a process called collective invasion, in which cohesive
      groups of cells invade through interstitial tissue. Here, we identified an
      epigenetically distinct subpopulation of breast tumor cells that have an enhanced
      capacity to collectively invade. Analysis of spheroid invasion in an organotypic
      culture system revealed that these "trailblazer" cells are capable of initiating
      collective invasion and promote non-trailblazer cell invasion, indicating a
      commensal relationship among subpopulations within heterogenous tumors. Canonical
      mesenchymal markers were not sufficient to distinguish trailblazer cells from non
      trailblazer cells, suggesting that defining the molecular underpinnings of the
      trailblazer phenotype could reveal collective invasion-specific mechanisms.
      Functional analysis determined that DOCK10, ITGA11, DAB2, PDFGRA, VASN, PPAP2B,
      and LPAR1 are highly expressed in trailblazer cells and required to initiate
      collective invasion, with DOCK10 essential for metastasis. In patients with
      triple-negative breast cancer, expression of these 7 genes correlated with poor
      outcome. Together, our results indicate that spontaneous conversion of the
      epigenetic state in a subpopulation of cells can promote a transition from in
      situ to invasive growth through induction of a cooperative form of collective
      invasion and suggest that therapeutic inhibition of trailblazer cell invasion may
      help prevent metastasis. 

PMID- 25844903
TI  - Stable nanoparticles prepared by heating electrostatic complexes of whey protein
      isolate-dextran conjugate and chondroitin sulfate.
AB  - A simple and green method was developed for preparing the stable biopolymer
      nanoparticles with pH and salt resistance. The method involved the macromolecular
      crowding Maillard process and heat-induced gelation process. The conjugates of
      whey protein isolate (WPI) and dextran were produced by Maillard reaction. The
      nanoparticles were fabricated by heating electrostatic complexes of WPI-dextran
      conjugate and chondroitin sulfate (ChS) above the denaturation temperature and
      near the isoelectric point of WPI. Then, the nanoparticles were characterized by
      spectrophotometry, dynamic laser scattering, zeta potential, transmission
      electron microscopy, atomic force microscopy, and scanning electron microscopy.
      Results showed that the nanoparticles were stable in the pH range from 1.0 to 8.0
      and in the presence of high salt concentration of 200 mM NaCl. WPI-dextran
      conjugate, WPI, and ChS were assembled into the nanoparticles with dextran
      conjugated to WPI/ChS shell and WPI/ChS core. The repulsive steric interactions,
      from both dextran covalently conjugated to WPI and ChS electrostatically
      interacted with WPI, were the major formation mechanism of the stable
      nanoparticles. As a nutrient model, lutein could be effectively encapsulated into
      the nanoparticles. Additionally, the nanoparticles exhibited a spherical shape
      and homogeneous size distribution regardless of lutein loading. The results
      suggested that the stable nanoparticles from proteins and strong polyelectrolyte
      polysaccharides would be used as a promising target delivery system for
      hydrophobic nutrients and drugs at physiological pH and salt conditions. 

PMID- 25844904
TI  - Automatic detection of confusion in elderly users of a web-based health
      instruction video.
AB  - BACKGROUND: Because of cognitive limitations and lower health literacy, many
      elderly patients have difficulty understanding verbal medical instructions.
      Automatic detection of facial movements provides a nonintrusive basis for
      building technological tools supporting confusion detection in healthcare
      delivery applications on the Internet. MATERIALS AND METHODS: Twenty-four elderly
      participants (70-90 years old) were recorded while watching Web-based health
      instruction videos involving easy and complex medical terminology. Relevant
      fragments of the participants' facial expressions were rated by 40 medical
      students for perceived level of confusion and analyzed with automatic software
      for facial movement recognition. RESULTS: A computer classification of the
      automatically detected facial features performed more accurately and with a
      higher sensitivity than the human observers (automatic detection and
      classification, 64% accuracy, 0.64 sensitivity; human observers, 41% accuracy,
      0.43 sensitivity). A drill-down analysis of cues to confusion indicated the
      importance of the eye and eyebrow region. CONCLUSIONS: Confusion caused by
      misunderstanding of medical terminology is signaled by facial cues that can be
      automatically detected with currently available facial expression detection
      technology. The findings are relevant for the development of Web-based services
      for healthcare consumers.

PMID- 25844901
TI  - 12/15-Lipoxygenase-mediated enzymatic lipid oxidation regulates DC maturation and
      function.
AB  - DCs are able to undergo rapid maturation, which subsequently allows them to
      initiate and orchestrate T cell-driven immune responses. DC maturation must be
      tightly controlled in order to avoid random T cell activation and development of
      autoimmunity. Here, we determined that 12/15-lipoxygenase-meditated (12/15-LO
      mediated) enzymatic lipid oxidation regulates DC activation and fine-tunes
      consecutive T cell responses. Specifically, 12/15-LO activity determined the DC
      activation threshold via generation of phospholipid oxidation products that
      induced an antioxidative response dependent on the transcription factor NRF2.
      Deletion of the 12/15-LO-encoding gene or pharmacologic inhibition of 12/15-LO in
      murine or human DCs accelerated maturation and shifted the cytokine profile,
      thereby favoring the differentiation of Th17 cells. Exposure of 12/15-LO
      deficient DCs to 12/15-LO-derived oxidized phospholipids attenuated both DC
      activation and the development of Th17 cells. Analysis of lymphatic tissues from
      12/15-LO-deficient mice confirmed enhanced maturation of DCs as well as an
      increased differentiation of Th17 cells. Moreover, experimental autoimmune
      encephalomyelitis in mice lacking 12/15-LO resulted in an exacerbated Th17-driven
      autoimmune disease. Together, our data reveal that 12/15-LO controls maturation
      of DCs and implicate enzymatic lipid oxidation in shaping the adaptive immune
      response. 

PMID- 25844902
TI  - Gq signaling causes glomerular injury by activating TRPC6.
AB  - Familial forms of focal segmental glomerulosclerosis (FSGS) have been linked to
      gain-of-function mutations in the gene encoding the transient receptor potential
      channel C6 (TRPC6). GPCRs coupled to Gq signaling activate TRPC6, suggesting that
      Gq-dependent TRPC6 activation underlies glomerular diseases. Here, we developed a
      murine model in which a constitutively active Gq alpha subunit (Gq(Q209L),
      referred to herein as GqQ>L) is specifically expressed in podocytes and examined
      the effects of this mutation in response to puromycin aminonucleoside (PAN)
      nephrosis. We found that compared with control animals, animals expressing GqQ>L
      exhibited robust albuminuria, structural features of FSGS, and reduced numbers of
      glomerular podocytes. Gq activation stimulated calcineurin (CN) activity,
      resulting in CN-dependent upregulation of TRPC6 in murine kidneys. Deletion of
      TRPC6 in GqQ>L-expressing mice prevented FSGS development and inhibited both
      tubular damage and podocyte loss induced by PAN nephrosis. Similarly,
      administration of the CN inhibitor FK506 reduced proteinuria and tubular injury
      but had more modest effects on glomerular pathology and podocyte numbers in
      animals with constitutive Gq activation. Moreover, these Gq-dependent effects on
      podocyte injury were generalizable to diabetic kidney disease, as expression of
      GqQ>L promoted albuminuria, mesangial expansion, and increased glomerular
      basement membrane width in diabetic mice. Together, these results suggest that
      targeting Gq/TRPC6 signaling may have therapeutic benefits for the treatment of
      glomerular diseases.

PMID- 25844905
TI  - Trust in deliberation: The consequences of deliberative decision strategies for
      medical decisions.
AB  - OBJECTIVE: Decision aids (DAs) play an increasingly critical role in supporting
      patients in making preference-sensitive treatment decisions. One largely untested
      assumption of DA design is that patients should be encouraged to deliberate
      carefully about their options after being informed of those options. The purpose
      of the present research is to test the impact of deliberative versus intuitive
      decision strategies in medical decision contexts. METHOD: In 3 experiments,
      participants were randomly assigned to make a hypothetical medical decision
      either intuitively, or using various deliberative strategies. In Study 1, we
      predicted that deliberation would improve decision confidence while not changing
      decisions. In Study 2, our aim was to establish whether the observed increase in
      confidence was due to decision-making effort, confirmation bias, or both. In
      Study 3, it was predicted that deliberation would cause participants to become
      more confident in suboptimal decisions. RESULTS: Across 3 studies, participants
      who deliberated felt better about their decisions and decision process, even when
      the decision was the same as what would have been chosen intuitively (Studies 1
      and 2), and even when the decision was normatively bad (Study 3). Study 2
      additionally indicated that participants' confidence was driven by confirmation
      bias rather than effort justification. CONCLUSIONS: Deliberative tasks may often
      fail to be an effective debiasing tool, and components of patient decision aids
      that ask patients to deliberate may serve to improve how patients feel without
      improving the quality of their decisions.

PMID- 25844906
TI  - Association between trajectories of maternal depression and subsequent
      psychological functioning in youth with and without chronic physical illness.
AB  - OBJECTIVES: The aim of this study was to determine if the presence of youth
      chronic illness moderates the association between trajectories of maternal
      depressive symptoms and psychological functioning in youths. METHODS: Data came
      from the National Longitudinal Survey of Children and Youth (N = 11,813). Using
      the 12-item version of the Center for Epidemiological Studies Depression Scale
      (CES-D), symptom trajectories were estimated by latent class growth modeling over
      3 measurement occasions (when their children were 10-11, 12-13, and 14-15 years).
      The moderating effect of youth chronic illness on the association between
      maternal depression and youth psychological functioning at 16-19 years was tested
      using multiple regression. Three measures of psychological functioning were
      assessed: anger regulation (Bar-On Emotional Quotient Inventory), self-concept
      (Self-Determination Questionnaire), and depressive symptoms (CES-D). RESULTS:
      Four trajectories (low, decreasing, increasing, high) of maternal depression were
      identified. The association of maternal depressive symptoms on youth
      psychological functioning was modified by chronic illness; less favorable
      trajectories of maternal depression had a more pronounced detrimental association
      on youths with chronic illness compared to controls. CONCLUSIONS: Youths with
      chronic illness are particularly vulnerable to the negative psychological
      exposure of maternal depressive symptoms during the transition to adulthood.
      Family-centered transition of care programs in the medical setting may be
      beneficial in reducing the association between symptoms of maternal depression
      and youth psychological functioning.

PMID- 25844907
TI  - Relationships among spousal communication, self-efficacy, and motivation among
      expectant Latino fathers who smoke.
AB  - OBJECTIVE: Cigarette smoking is a prevalent problem among Latinos, yet little is
      known about what factors motivate them to quit smoking or make them feel more
      confident that they can. Given cultural emphases on familial bonds among Latinos
      (e.g., familismo), it is possible that communication processes among Latino
      spouses play an important role. The present study tested a mechanistic model in
      which perceived spousal constructive communication patterns predicted changes in
      level of motivation for smoking cessation through changes in self-efficacy among
      Latino expectant fathers. METHODS: Latino males (n = 173) and their pregnant
      partners participated in a couple-based intervention targeting males' smoking.
      Couples completed self-report measures of constructive communication, self
      efficacy (male partners only), and motivation to quit (male partners only) at 4
      time points throughout the intervention. RESULTS: Higher levels of perceived
      constructive communication among Latino male partners predicted subsequent
      increases in male partners' self-efficacy and, to a lesser degree, motivation to
      quit smoking; however, self-efficacy did not mediate associations between
      constructive communication and motivation to quit smoking. Furthermore, positive
      relationships with communication were only significant at measurements taken
      after completion of the intervention. Female partners' level of perceived
      constructive communication did not predict male partners' outcomes. CONCLUSION:
      These results provide preliminary evidence to support the utility of couple-based
      interventions for Latino men who smoke. Findings also suggest that perceptions of
      communication processes among Latino partners (particularly male partners) may be
      an important target for interventions aimed at increasing desire and perceived
      ability to quit smoking among Latino men. (PsycINFO Database Record

PMID- 25844908
TI  - Leadership styles, emotion regulation, and burnout.
AB  - This study investigated the potential impact of leadership style on leaders'
      emotional regulation strategies and burnout. Drawing on the full-range model of
      leadership and Conservation of Resources (COR) theory, we tested whether
      transformational, contingent reward, management by exception-active and -passive,
      or laissez-faire leadership exert direct effects on leaders' reported use of
      surface acting, deep acting, and genuine emotion. In turn, we hypothesized and
      tested the indirect effect of leadership on burnout through surface acting. Three
      waves of data from 205 leaders were analyzed using OLS regression.
      Transformational leadership predicted deep acting and genuine emotion. Contingent
      reward predicted both surface and deep acting. Management by exception-active and
      -passive predicted surface acting, and laissez faire predicted genuine emotion.
      The indirect effects of management by exception-active and -passive on burnout
      through surface acting were not significant. Indirect effects of transformational
      leadership and laissez-faire on burnout through genuine emotion, however, were
      significant. This study provides empirical evidence for the hypothesized
      relationships between leadership style, emotion regulation, and burnout, and
      provides the basis for future research and theory building on this topic.

PMID- 25844909
TI  - Managing disclosure of personal information: An opportunity to enhance supported
      employment.
AB  - OBJECTIVE: To first provide an overview of studies that explore mental health
      disclosure in the workplace; including factors that influence the decision to
      disclose, and differing approaches to disclosure (binary, multidimensional, and
      evolving and ongoing). Second, to provide a critical overview of existing tools
      designed to help clients manage their mental health disclosure decisions. METHOD:
      Electronic searches of PubMed, PsycINFO and ScienceDirect were undertaken,
      excluding all articles published prior to 1990. The following search terms were
      used: mental health disclosure, employment, severe and persistent mental illness,
      psychosis, schizophrenia, supported employment, individual placement and support
      (IPS). RESULTS: We found that mental health disclosure involves a complex
      decision-making process, and yet clients of IPS supported employment are
      currently provided with little structured guidance on how to manage their
      personal information in the workplace. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE:
      More extensive investigations are required of existing mental health disclosure
      tools before they can be developed into a standardized intervention for
      practitioners. However, preliminary evidence suggests that facilitating better
      disclosure decisions and management of personal information is a promising area
      of future research. This line of investigation is likely to find ways to enhance
      competitive employment outcomes in supported employment for people with severe
      and persistent mental illness.

PMID- 25844911
TI  - Stress-related personal growth among emerging adults whose mothers have been
      diagnosed with mental illness.
AB  - OBJECTIVE: This study explored whether emerging adults' reports of their
      relationships with their mothers who have been diagnosed with mental illness and
      their attempts to make meaning of the experience of having a mother with mental
      illness were associated with stress-related personal growth. METHODS: Fifty-two
      emerging adult children with mothers who have been diagnosed with mental illness
      responded to a self-report questionnaire containing measures of adult parent
      child relationships, meaning making, and stress-related personal growth. RESULTS:
      Hierarchical multiple linear regression analysis of the cross-sectional data
      indicated that meaning making contributed to stress-related personal growth after
      accounting for emerging adult-mother relationship factors. Aspects of the
      emerging adult-mother relationship did not contribute to growth. CONCLUSIONS:
      Efforts to make meaning of having a mother with mental illness may facilitate
      growth among emerging adult children. Longitudinal investigations in larger
      samples are needed to better understand the relationship among interpersonal
      relationships, meaning making, and growth in this population. IMPLICATIONS FOR
      PRACTICE: Interventions with adult children of people with mental illness should
      address their capacity for personal growth.

PMID- 25844910
TI  - From discrimination to internalized mental illness stigma: The mediating roles of
      anticipated discrimination and anticipated stigma.
AB  - OBJECTIVE: Internalizing mental illness stigma is related to poorer well-being,
      but less is known about the factors that predict levels of internalized stigma.
      This study explored how experiences of discrimination relate to greater
      anticipation of discrimination and devaluation in the future and how anticipation
      of stigma in turn predicts greater stigma internalization. METHOD: Participants
      were 105 adults with mental illness who self-reported their experiences of
      discrimination based on their mental illness, their anticipation of
      discrimination and social devaluation from others in the future, and their level
      of internalized stigma. Participants were approached in several locations and
      completed surveys on laptop computers. RESULTS: Correlational analyses indicated
      that more experiences of discrimination due to one's mental illness were related
      to increased anticipated discrimination in the future, increased anticipated
      social stigma from others, and greater internalized stigma. Multiple serial
      mediator analyses showed that the effect of experiences of discrimination on
      internalized stigma was fully mediated by increased anticipated discrimination
      and anticipated stigma. CONCLUSION AND IMPLICATIONS FOR PRACTICE: Experiences of
      discrimination over one's lifetime may influence not only how much future
      discrimination people with mental illness are concerned with but also how much
      they internalize negative feelings about the self. Mental health professionals
      may need to address concerns with future discrimination and devaluation in order
      to decrease internalized stigma.

PMID- 25844912
TI  - Next-generation psychiatric assessment: Using smartphone sensors to monitor
      behavior and mental health.
AB  - OBJECTIVE: Optimal mental health care is dependent upon sensitive and early
      detection of mental health problems. We have introduced a state-of-the-art method
      for the current study for remote behavioral monitoring that transports assessment
      out of the clinic and into the environments in which individuals negotiate their
      daily lives. The objective of this study was to examine whether the information
      captured with multimodal smartphone sensors can serve as behavioral markers for
      one's mental health. We hypothesized that (a) unobtrusively collected smartphone
      sensor data would be associated with individuals' daily levels of stress, and (b)
      sensor data would be associated with changes in depression, stress, and
      subjective loneliness over time. METHOD: A total of 47 young adults (age range:
      19-30 years) were recruited for the study. Individuals were enrolled as a single
      cohort and participated in the study over a 10-week period. Participants were
      provided with smartphones embedded with a range of sensors and software that
      enabled continuous tracking of their geospatial activity (using the Global
      Positioning System and wireless fidelity), kinesthetic activity (using multiaxial
      accelerometers), sleep duration (modeled using device-usage data, accelerometer
      inferences, ambient sound features, and ambient light levels), and time spent
      proximal to human speech (i.e., speech duration using microphone and speech
      detection algorithms). Participants completed daily ratings of stress, as well as
      pre- and postmeasures of depression (Patient Health Questionnaire-9; Spitzer,
      Kroenke, & Williams, 1999), stress (Perceived Stress Scale; Cohen et al., 1983),
      and loneliness (Revised UCLA Loneliness Scale; Russell, Peplau, & Cutrona, 1980).
      RESULTS: Mixed-effects linear modeling showed that sensor-derived geospatial
      activity (p < .05), sleep duration (p < .05), and variability in geospatial
      activity (p < .05), were associated with daily stress levels. Penalized
      functional regression showed associations between changes in depression and
      sensor-derived speech duration (p < .05), geospatial activity (p < .05), and
      sleep duration (p < .05). Changes in loneliness were associated with sensor
      derived kinesthetic activity (p < .01). CONCLUSIONS AND IMPLICATIONS FOR
      PRACTICE: Smartphones can be harnessed as instruments for unobtrusive monitoring
      of several behavioral indicators of mental health. Creative leveraging of
      smartphone sensing could provide novel opportunities for close-to-invisible
      psychiatric assessment at a scale and efficiency that far exceeds what is
      currently feasible with existing assessment technologies.

PMID- 25844913
TI  - Factors affecting implementation of an evidence-based practice in the Veterans
      Health Administration: Illness management and recovery.
AB  - OBJECTIVE: Illness management and recovery (IMR) is an evidence-based practice
      that assists consumers in managing their illnesses and pursuing personal recovery
      goals. Although research has examined factors affecting IMR implementation
      facilitated by multifaceted, active roll-outs, the current study attempted to
      elucidate factors affecting IMR implementation outside the context of a research
      driven implementation. METHODS: Semi-structured interviews with 20 local recovery
      coordinators and 18 local IMR experts were conducted at 23 VA medical centers.
      Interviews examined perceived and experienced barriers and facilitators to IMR
      implementation. Data were analyzed via thematic inductive/deductive analysis in
      the form of crystallization/immersion. RESULTS: Six factors differed between
      sites implementing IMR from those not providing IMR: awareness of IMR, importer
      champions, autonomy-supporting leadership, veteran-centered care, presence of a
      sensitive period, and presence of a psychosocial rehabilitation and recovery
      center. Four factors were common in both groups: recovery orientation, evidence
      based practices orientation, perceived IMR fit within program structure, and
      availability of staff time. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: IMR can be
      adopted in lieu of active implementation support; however, knowledge
      dissemination appears to be key. Future research should examine factors affecting
      the quality of implementation.

PMID- 25844914
TI  - How are perceived stigma, self-stigma, and self-reliance related to treatment
      seeking? A three-path model.
AB  - OBJECTIVE: Many college students may experience mental health problems but do not
      seek treatment from mental health professionals. The present study examined how
      perceived stigma and self-stigma toward seeking mental health treatment, as well
      as perceptions of self-reliance for coping with mental health problems, relate to
      college student treatment-seeking. METHOD: In total, 246 students completed a
      self-report survey that included measures of perceived stigma and self-stigma for
      treatment-seeking, self-reliance for addressing mental health concerns, self
      reported mental health problems, symptoms of depression and alcohol-related
      problems, attitudes toward treatment-seeking, and treatment-seeking behavior.
      RESULTS: Regression analyses revealed that higher perceived stigma, self-stigma,
      and self-reliance were all related to a more negative attitude toward treatment
      seeking. In a 3-path mediation model, bootstrapping results indicated an indirect
      effect where perceived stigma was related to attitude toward treatment-seeking
      and treatment-seeking behaviors through self-stigma and self-reliance.
      Specifically, higher perceived stigma was related to higher self-stigma, higher
      self-stigma was related to higher self-reliance, and higher self-reliance was
      associated with a more negative attitude toward treatment-seeking in the overall
      sample, and a decreased probability of having sought treatment among those who
      screened positive for a mental health problem. CONCLUSIONS AND IMPLICATIONS FOR
      PRACTICE: Perceived stigma may influence whether or not college students seek
      treatment for mental health problems by potentially increasing stigmatizing
      attitudes toward themselves and increasing preferences for handling problems on
      their own. Researchers and practitioners are recommended to seek a better
      understanding of the complex treatment barriers to reduce stigma and facilitate
      treatment-seeking.

PMID- 25844915
TI  - The relationship between cognition, job complexity, and employment duration in
      first-episode psychosis.
AB  - OBJECTIVE: To investigate the relationship between cognition and employment
      duration in first-episode psychosis (FEP), and establish if a "fit" between
      cognition and job complexity is associated with longer employment duration.
      METHOD: This study involved secondary data analysis of a subsample of FEP
      individuals (n = 65) who participated in a randomized controlled trial comparing
      Individual Placement and Support plus treatment as usual (TAU), versus TAU alone,
      over 6 months. A cognitive battery was administered at baseline and employment
      duration (hours) and job complexity in the longest held job over 6 months were
      measured. RESULTS: Factor analysis with promax rotation of the cognitive battery
      revealed 4 cognitive domains: (a) attention and processing speed; (b) verbal
      learning and memory; (c) verbal comprehension and fluency; and (d) visual
      organization and memory (VO&M). The final hierarchical regression model found
      that VO&M and job complexity independently predicted employment duration in
      longest held job; however, the "fit" (or interaction) between VO&M and job
      complexity was not significant. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: These
      findings suggest that VO&M and job complexity are important predictors of
      employment duration, but it is not necessary to ensure VO&M ability matches job
      complexity. However, there are limited comparative studies in this area, and
      other aspects of the person-organization fit perspective may still be useful to
      optimize vocational outcomes in FEP.

PMID- 25844917
TI  - Inactivation of Mandelate Racemase by 3-Hydroxypyruvate Reveals a Potential
      Mechanistic Link between Enzyme Superfamilies.
AB  - Mandelate racemase (MR), a member of the enolase superfamily, catalyzes the
      Mg(2+)-dependent interconversion of the enantiomers of mandelate. Several alpha
      keto acids are modest competitive inhibitors of MR [e.g., mesoxalate (Ki = 1.8 +/
      0.3 mM) and 3-fluoropyruvate (Ki = 1.3 +/- 0.1 mM)], but, surprisingly, 3
      hydroxypyruvate (3-HP) is an irreversible, time-dependent inhibitor (kinact/KI =
      83 +/- 8 M(-1) s(-1)). Protection from inactivation by the competitive inhibitor
      benzohydroxamate, trypsinolysis and electrospray ionization tandem mass
      spectrometry analyses, and X-ray crystallographic studies reveal that 3-HP
      undergoes Schiff-base formation with Lys 166 at the active site, followed by
      formation of an aldehyde/enol(ate) adduct. Such a reaction is unprecedented in
      the enolase superfamily and may be a relic of an activity possessed by a
      promiscuous progenitor enzyme. The ability of MR to form and deprotonate a Schiff
      base intermediate furnishes a previously unrecognized mechanistic link to other
      alpha/beta-barrel enzymes utilizing Schiff-base chemistry and is in accord with
      the sequence- and structure-based hypothesis that members of the metal-dependent
      enolase superfamily and the Schiff-base-forming N-acetylneuraminate lyase
      superfamily and aldolases share a common ancestor.

PMID- 25844916
TI  - A pilot study of the Nutrition and Exercise for Wellness and Recovery (NEW-R): A
      weight loss program for individuals with serious mental illnesses.
AB  - OBJECTIVE: This purpose of this study was to evaluate the Nutrition and Exercise
      for Wellness and Recovery (NEW-R) weight loss intervention. METHOD: Using a
      pretest/posttest design, 18 participants recruited from a community-based mental
      health program were assessed at baseline, immediately following the intervention
      (8 weeks), and at 6-month follow-up. The intervention was delivered by an
      occupational therapist and occupational therapy graduate students and consisted
      of 8 weekly sessions lasting 2 hr. Outcomes included changes in weight, and
      levels of knowledge about nutrition and exercise. RESULTS: Participants lost an
      average of 3 pounds at immediate postintervention, and lost an average of 10
      pounds at the 6-month follow-up. Participants also demonstrated significant
      increases in their knowledge about nutrition and physical activity. CONCLUSIONS
      AND IMPLICATIONS FOR PRACTICE: The results of this study provide preliminary
      support for the impact of the NEW-R intervention on weight loss and knowledge
      about diet and exercise.

PMID- 25844918
TI  - Porous polystyrene-block-poly(acrylic acid)/hemoglobin membrane formed by dually
      driven self-assembly and electrochemical application.
AB  - This study demonstrated a facile method to form a porous polymeric membrane,
      immobilizing a biocatalyst. A polyelectrolyte-based amphiphilic diblock
      copolymer, i.e., polystyrene-block-poly(acrylic acid) (PS-b-PAA), self-assembled
      with hemoglobin (Hb) dually driven by charge and amphiphilicity during solution
      casting and evaporation. XPS and contact angle measurements suggested that the PS
      block enriched on the membrane surface. The PAA block pointed toward the internal
      membrane as well as ordered the Hb arrangement at the interface of the polymer
      and electrode. The obtained PS-b-PAA/Hb electrode showed a remarkably enhanced
      direct electron transfer (ET), which was revealed to be a surface-controlled
      process accompanied by single-proton transfer. The membrane was tested to
      catalyze the reduction of hydrogen peroxide, and exhibited an excellent
      reproducibility and stability. This method with a charge and amphiphilicity
      dually driven (CADD) self-assembly opened up a new way to construct a third
      generation electrochemical biosensor. 

PMID- 25844919
TI  - Charge percolation pathways guided by defects in quantum dot solids.
AB  - Charge hopping and percolation in quantum dot (QD) solids has been widely
      studied, but the microscopic nature of the percolation process is not understood
      or determined. Here we present the first imaging of the charge percolation
      pathways in two-dimensional PbS QD arrays using Kelvin probe force microscopy
      (KPFM). We show that under dark conditions electrons percolate via in-gap states
      (IGS) instead of the conduction band, while holes percolate via valence band
      states. This novel transport behavior is explained by the electronic structure
      and energy level alignment of the individual QDs, which was measured by scanning
      tunneling spectroscopy (STS). Chemical treatments with hydrazine can remove the
      IGS, resulting in an intrinsic defect-free semiconductor, as revealed by STS and
      surface potential spectroscopy. The control over IGS can guide the design of
      novel electronic devices with impurity conduction, and photodiodes with
      controlled doping. 

PMID- 25844921
TI  - Mapping pixel dissimilarity in wide-field super-resolution fluorescence
      microscopy.
AB  - Recent advances in fluorescence bioimaging with single-molecule sensitivity have
      relied on the analysis and visualization of single-molecule data obtained on
      smart fluorophores. We describe an alternative method to enhance the information
      content of densely labeled fluorescence images. Visualization is improved by
      representing pixels as the dissimilarities of the fluctuations of the
      fluorescence signals, with the dissimilarity being taken to the mean of the
      signals over all the pixels. Mapping pixel dissimilarity (Mappix) results in
      signal and information enhancement of the output images. In addition, the spatial
      distribution of the fluorescence brightness of the original image is not skewed.
      This allows large differences of molecular brightness to be handled which turns
      out to be critical to the fidelity of the final image. In this work, we provide
      testing of the Mappix approach with both simulated and real data. The results
      obtained on HEK cells expressing Dronpa photoswitchable fluorescent protein show
      that, for densely labeled samples, improvement can be obtained on fluorescence
      images allowing the observation of structural information. Despite some
      limitations, comparison to state of art methods reveals that Mappix can be very
      useful for biological imaging applications. 

PMID- 25844922
TI  - Probing the Effect of miRNA on siRNA-PEI Polyplexes.
AB  - Delivery of small interfering RNA (siRNA) for silencing of aberrantly expressed
      genes is a promising therapy for the treatment of various genetic disorders.
      Polymeric carriers have been used in the design of efficient delivery systems to
      generate nanoscale siRNA polyplexes. Despite the great amount of research pursued
      on siRNA therapeutics, the underlying mechanisms of polyplex dissociation in
      cytosol are still unclear. The fate of siRNA polyplexes during intracellular
      stages of delivery and how the endogenous molecules may affect the integrity of
      polyplexes remains to be explored. In this study, we have focused on miRNA-21 as
      a representative anionic endogenous molecule and performed gel electrophoresis
      mobility shift assays, particle size and zeta (zeta)-potential analyses, and a
      series of all-atom molecular dynamics simulations to elucidate the effect of
      miRNA on siRNA-PEI polyplexes. We report a slightly better binding to PEI by
      miRNA than that of siRNA, and speculated that miRNA may disrupt the integrity of
      preformed siRNA-PEI polyplexes. In contrast to our initial speculation, however,
      introduction of miRNA to a preformed siRNA-PEI polyplex revealed formation of a
      miRNA layer surrounding the polyplex through interactions with PEI. The resulting
      structure is a ternary siRNA-PEI-miRNA complex, where the experimentally
      determined zeta-potential was found to decrease as a function of miRNA added. 

PMID- 25844923
TI  - Alkali-templated surface nanopatterning of chalcogenide thin films: a novel
      approach toward solar cells with enhanced efficiency.
AB  - Concepts of localized contacts and junctions through surface passivation layers
      are already advantageously applied in Si wafer-based photovoltaic technologies.
      For Cu(In,Ga)Se2 thin film solar cells, such concepts are generally not applied,
      especially at the heterojunction, because of the lack of a simple method yielding
      features with the required size and distribution. Here, we show a novel,
      innovative surface nanopatterning approach to form homogeneously distributed
      nanostructures (<30 nm) on the faceted, rough surface of polycrystalline
      chalcogenide thin films. The method, based on selective dissolution of self
      assembled and well-defined alkali condensates in water, opens up new research
      opportunities toward development of thin film solar cells with enhanced
      efficiency. 

PMID- 25844924
TI  - Application of a high-throughput analyzer in evaluating solid adsorbents for post
      combustion carbon capture via multicomponent adsorption of CO2, N2, and H2O.
AB  - Despite the large number of metal-organic frameworks that have been studied in
      the context of post-combustion carbon capture, adsorption equilibria of gas
      mixtures including CO2, N2, and H2O, which are the three biggest components of
      the flue gas emanating from a coal- or natural gas-fired power plant, have never
      been reported. Here, we disclose the design and validation of a high-throughput
      multicomponent adsorption instrument that can measure equilibrium adsorption
      isotherms for mixtures of gases at conditions that are representative of an
      actual flue gas from a power plant. This instrument is used to study 15 different
      metal-organic frameworks, zeolites, mesoporous silicas, and activated carbons
      representative of the broad range of solid adsorbents that have received
      attention for CO2 capture. While the multicomponent results presented in this
      work provide many interesting fundamental insights, only adsorbents
      functionalized with alkylamines are shown to have any significant CO2 capacity in
      the presence of N2 and H2O at equilibrium partial pressures similar to those
      expected in a carbon capture process. Most significantly, the amine-appended
      metal organic framework mmen-Mg2(dobpdc) (mmen = N,N'-dimethylethylenediamine,
      dobpdc (4-) = 4,4'-dioxido-3,3'-biphenyldicarboxylate) exhibits a record CO2
      capacity of 4.2 +/- 0.2 mmol/g (16 wt %) at 0.1 bar and 40  degrees C in the
      presence of a high partial pressure of H2O. 

PMID- 25844925
TI  - Life cycle assessment of a novel closed-containment salmon aquaculture
      technology.
AB  - In salmonid aquaculture, a variety of technologies have been deployed that
      attempt to limit a range of environmental impacts associated with net-pen
      culture. One such technology employs a floating, solid-walled enclosure as the
      primary culture environment, providing greater potential control over negative
      interactions with surroundings waters while limiting energy use required for
      water circulation, thermo-regulation and supplemental oxygen provision. Here, we
      utilize life cycle assessment to model contributions to a suite of global-scale
      resource depletion and environmental concerns (including global warming
      potential, acidification potential, marine eutrophication potential, cumulative
      energy use, and biotic resource use) of such a technology deployed commercially
      to rear Chinook salmon in coastal British Columbia, Canada. Results indicate that
      at full grow-out, feed provisioning and on-site energy use dominate contributions
      across four of five impact categories assessed. For example, per tonne of salmon
      harvested, feed contributed approximately 72% to global warming potential, 72% to
      acidification potential, and accounted for 100% of biotic resource use. However,
      for both feed and on-site energy use, impacts are heavily influenced by specific
      sources of inputs; therefore efforts to improve the environmental performance of
      this technology should focus on reducing these in favor of less impactful
      alternatives. 

PMID- 25844927
TI  - I will speak up if my voice is socially desirable: A moderated mediating process
      of promotive versus prohibitive voice.
AB  - Employees are likely to speak up if they perceive high efficacy and low risk
      associated with such behavior, that is, if they perceive voice is socially
      desirable. Drawing on socially desirable responding (SDR) theory, we reason that
      individual value on power distance and supervisory delegation are related to the
      agentic motive for SDR, and that these 2 factors interact to influence employees'
      perceived efficacy of voice. We also identify individual value on superficial
      harmony and group voice climate, which are both relevant to the communal motive
      for SDR, jointly affect perceived risk of voice. Furthermore, by influencing
      perceived efficacy and perceived risk, these interactive forces would be
      differentially related to promotive versus prohibitive voice. Data from 66 middle
      managers and 262 of their direct reports in 5 high-tech firms provide
      considerable support for our hypothesized moderated mediation model. Supervisory
      delegation weakens the negative relationship between power distance and perceived
      efficacy of promotive voice, and the indirect relationship between power distance
      and promotive voice via perceived efficacy. In contrast, group voice climate
      weakens the positive relationship between superficial harmony and perceived risk
      of prohibitive voice, which mediates the indirect relationship between
      superficial harmony and prohibitive voice. We discuss the theoretical and
      practical implications of our findings in organizational settings.

PMID- 25844926
TI  - Developmental regulation and induction of cytochrome P450 2W1, an enzyme
      expressed in colon tumors.
AB  - Cytochrome P450 2W1 (CYP2W1) is expressed predominantly in colorectal and also in
      hepatic tumors, whereas the levels are insignificant in the corresponding normal
      human adult tissues. CYP2W1 has been proposed as an attractive target for
      colorectal cancer (CRC) therapy by exploiting its ability to activate duocarmycin
      prodrugs to cytotoxic metabolites. However, its endogenous function, regulation
      and developmental pattern of expression remain unexplored. Here we report the
      CYP2W1 developmental expression in the murine and human gastrointestinal tissues.
      The gene expression in the colon and small intestine commence at early stages of
      embryonic life and is completely silenced shortly after the birth.
      Immunohistochemical analysis of human fetal colon revealed that CYP2W1 expression
      is restricted to the crypt cells. The silencing of CYP2W1 after birth correlates
      with the increased methylation of CpG-rich regions in both murine and human
      CYP2W1 genes. Analysis of CYP2W1 expression in the colon adenocarcinoma cell line
      HCC2998 revealed that the gene expression can be induced by e.g. the antitumor
      agent imatinib, linoleic acid and its derivatives. The imatinib mediated
      induction of CYP2W1 suggests an adjuvant therapy to treatment with duocarmycins
      that thus would involve induction of tumor CYP2W1 levels followed by the CYP2W1
      activated duocarmycin prodrugs. Taken together these data strongly support
      further exploration of CYP2W1 as a specific drug target in CRC. 

PMID- 25844929
TI  - The Coupling between Gold or Silver Nanocubes in Their Homo-Dimers: A New
      Coupling Mechanism at Short Separation Distances.
AB  - Using the DDA method, we investigated the near-field coupling between two excited
      Au or Ag 42 nm nanocubes in a face-to-face dimer configuration at small
      separation distances where the exponential coupling behavior distinctly changes.
      This could be due to the failure of the dipole approximation at short distances
      or a change in the electromagnetic field distribution between the adjacent
      monomers. A detailed calculation of the plasmonic field distribution strongly
      suggests that the latter mechanism is responsible for the failure of the expected
      exponential coupling behavior at small separation distances. The results suggest
      that the observed optical properties of the pair of Au or Ag nanocubes separated
      by distances larger than 6 nm, result from the electromagnetic coupling between
      the oscillating dipoles at the corners of the adjacent facets of the nanocubes.
      At separations smaller than 6 nm, the distribution of the plasmonic dipoles along
      both the facets and the corners of the adjacent monomers control the plasmonic
      spectra and the distance dependent optical properties of the dimer. 

PMID- 25844928
TI  - The molecular epidemiology of Treponema pallidum subspecies pallidum.
AB  - Pathogens adapt and evolve in response to pressures exerted by host environments,
      leading to generation of genetically diverse variants. Treponema pallidum
      subspecies pallidum displays a substantial amount of interstrain diversity. These
      variants have been identified in various parts of the world, indicating
      transmission linkage between geographical regions. Genotyping is based on
      molecular characterisation of various loci in the syphilis treponeme genome, but
      still require further development and continued research, as new bacterial types
      are continually being detected. The goal for studying the molecular epidemiology
      of Treponema pallidum variants is the global monitoring of the transmission of
      genetically distinct organisms with different drug sensitivities and,
      potentially, different virulence proprieties. 

PMID- 25844931
TI  - High-Yield and Selective Photoelectrocatalytic Reduction of CO2 to Formate by
      Metallic Copper Decorated Co3O4 Nanotube Arrays.
AB  - Carbon dioxide (CO2) reduction to useful chemicals is of great significance to
      global climate and energy supply. In this study, CO2 has been
      photoelectrocatalytically reduced to formate at metallic Cu nanoparticles (Cu
      NPs) decorated Co3O4 nanotube arrays (NTs) with high yield and high selectivity
      of nearly 100%. Noticeably, up to 6.75 mmol.L(-1).cm(-2) of formate was produced
      in an 8 h photoelectrochemical process, representing one of the highest yields
      among those in the literature. The results of scanning electron microscopy,
      transmission electron microscopy and photoelectrochemical characterization
      demonstrated that the enhanced production of formate was attributable to the self
      supported Co3O4 NTs/Co structure and the interface band structure of Co3O4 NTs
      and metallic Cu NPs. Furthermore, a possible two-electron reduction mechanism on
      the selective PEC CO2 reduction to formate at the Cu-Co3O4 NTs was explored. The
      first electron reduction intermediate, CO2 ads*-, was adsorbed on Cu in the form
      of Cu-O. With the carbon atom suspended in solution, CO2 ads*- is readily
      protonated to form the HCOO- radical. And HCOO- as a product rapidly desorbs from
      the copper surface with a second electron transfer to the adsorbed species.

PMID- 25844930
TI  - Synthesis and pharmacology of halogenated delta-opioid-selective [d
      Ala(2)]deltorphin II peptide analogues.
AB  - Deltorphins are naturally occurring peptides produced by the skin of the giant
      monkey frog (Phyllomedusa bicolor). They are delta-opioid receptor-selective
      agonists. Herein, we report the design and synthesis of a peptide, Tyr-d-Ala
      (pI)Phe-Glu-Ile-Ile-Gly-NH2 3 (GATE3-8), based on the [d-Ala(2)]deltorphin II
      template, which is delta-selective in in vitro radioligand binding assays over
      the MU- and kappa-opioid receptors. It is a full agonist in [(35)S]GTPgammaS
      functional assays and analgesic when administered supraspinally to mice.
      Analgesia of 3 (GATE3-8) is blocked by the selective delta receptor antagonist
      naltrindole, indicating that the analgesic action of 3 is mediated by the delta
      opioid receptor. We have established a radioligand in which (125)I is
      incorporated into 3 (GATE3-8). The radioligand has a KD of 0.1 nM in Chinese
      hamster ovary (CHO) cells expressing the delta receptor. Additionally, a series
      of peptides based on 3 (GATE3-8) was synthesized by incorporating various
      halogens in the para position on the aromatic ring of Phe(3). The peptides were
      characterized for binding affinity at the MU-, delta-, and kappa-opioid
      receptors, which showed a linear correlation between binding affinity and the
      size of the halogen substituent. These peptides may be interesting tools for
      probing delta-opioid receptor pharmacology. 

PMID- 25844920
TI  - Gold(I)-Catalyzed Activation of Alkynes for the Construction of Molecular
      Complexity.

PMID- 25844933
TI  - Synthesis of alpha-amino acidato derivatives of niobium and tantalum pentahalides
      and their conversion into iminium salts.
AB  - Dinuclear complexes of formula Nb2Cl9[O2CCH(R)NR'R"2-kappaO,kappaO] (R =
      CH2CHMe2, R' = R" = H, 1a; R = CH2Ph, R' = R" = H, 1b; R = CH2CH2SCH3, R' = R" =
      H, 1c; R = R' = H, R" = Me, 1d; R = CH2Ph, R' = R" = Me, 1e;
      Nb2Cl9[O2C?CH(CH2)3NH?], 1f) were prepared by allowing NbCl5 to react in
      dichloromethane with the appropriate alpha-amino acid in 1:2 amino acid/Nb molar
      ratio. The 1:1 reactions between MX5 (M = Nb, Ta; X = Cl, Br) and a series of
      alpha-amino acids resulted in the formation of the iminium salts
      [(R)CH?NR'R"2][MX6] (R = CH2Ph, R' = R" = Me: M = Nb, X = Cl, 2a; M = Nb, X = Br,
      2b; M = Ta, X = Cl, 2c; M = Ta, X = Br, 2d; R = CH2Ph, R' = R" = H, M = Nb: X =
      Cl, 3a; X = Br, 3b; R = CH2CHMe2, R' = R" = H, M = Nb, X = Cl, 4; R = R' = H, R"
      = Me, M = Nb, X = Cl, 5). The formate/amino acidate derivative
      NbCl3(O2CH)[O2CCH(CH2Ph)NMe2], 6, was isolated and identified as coproduct of the
      1:1 reaction between NbCl5 and N,N-dimethyl-l-phenylalanine, leading to 2a. All
      of the compounds were characterized by analytical and spectroscopic methods and
      by X-ray diffractometry in the cases of 2a, 2b, and 2d. Moreover, density
      functional theory studies were carried out to shed light on mechanistic and
      structural aspects. 

PMID- 25844932
TI  - Rapid initiation of intravenous epoprostenol infusion is the favored option in
      patients with advanced pulmonary arterial hypertension.
AB  - BACKGROUND: Intravenous infusion (IVI) of epoprostenol is an effective treatment
      for patients with advanced pulmonary arterial hypertension (PAH). However, there
      is no widely accepted standard method for initiating the IVI therapy. This study
      evaluated the hemodynamic improvements achieved with IVI epoprostenol to
      determine the optimal protocol for treatment initiation. METHODS AND RESULTS: We
      retrospectively analyzed 42 consecutive PAH patients who underwent IVI
      epoprostenol in Keio University Hospital from 2001 to 2013. The study group
      comprised 30 women with a mean age of 34.3 +/- 1.9 years. The etiology of PAH was
      idiopathic or heritable PAH (I/HPAH) in 38 cases, PAH associated with connective
      tissue disease in 3, and Eissenmenger's syndrome in the remaining case. We
      divided the patients into rapid- and slow-initiation therapy groups according to
      the cumulative epoprostenol dose administered during the first 180 days, and
      compared the hemodynamic changes between the groups. The median cumulative doses
      were 6142 +/- 165 MUg/kg and 3998 +/- 132 MUg/kg epoprostenol, respectively.
      While there were no significant differences in mean pulmonary artery pressure
      (mPAP), pulmonary vascular resistance (PVR), or cardiac index (CI) between the
      groups before the IVI epoprostenol therapy, the rapid-initiation therapy group
      achieved significant improvements in these hemodynamic data compared with the
      slow-initiation therapy group (P < 0.005) at the follow-up right-heart
      catheterization (RHC). CONCLUSION: Rapid initiation of IVI epoprostenol therapy
      achieved the optimal hemodynamic improvements in patients with severe PAH.

PMID- 25844935
TI  - Down Expression of FBP1 Is a Negative Prognostic Factor for Non-Small-Cell Lung
      Cancer.
AB  - Downregulation of fructose-1,6-bisphosphatse-1 (FBP1) was observed in several
      cancers but its role in the lung cancer still remains unknown. We examined the
      cancer tissues from 140 patients with nonsmall cell lung cancer patients and
      found that the relative gene expression of FBP1 was significantly lower in lung
      cancer tissues as compared to incisal marginal tissues and normal tissues. The
      patients with higher level of FBP1 RNA expression have significantly longer
      disease free survival and overall survival as compared to the lower expression
      groups. There was a negative correlation with the level of FBP1 and recurrence of
      the lung cancer. 

PMID- 25844936
TI  - Study of wetting on chemically soften interfaces by using combined solution
      thermodynamics and DFT calculations: forecasting effective softening elements.
AB  - Despite recent progress in understanding the wetting principles on soft solids,
      the roles of chemical bonding in the formation of interfaces have been largely
      ignored, because most of these studies are conducted at room temperatures. Here
      we propose a universal wetting principle from solution thermodynamics to account
      for the softening of both the solid and liquid surfaces (stable or metastable).
      Density functional theory (DFT) calculations are applied to evaluate the
      stability and electron transportation across the interfaces. We find that wetting
      is dominated by the system entropy changes involving not only the stable liquid
      alloy phase but also the metastable liquid oxide phases. The state-of-art
      multicomponent solution thermodynamic models and databases are applied to
      describe the entropy changes and predict the wetting behaviors. Our results show
      that by chemically softening either the liquid or the solid phase, the wetting
      angle reduces. And an effective soften agent/additive (either in the form of
      chemical elements or molecules) will weaken the bonds within the liquid (or
      solid) phase and promote new bonds at the interfaces, thus increasing the
      interface entropy. Subsequently, as an example, Ti and Zr are proposed as
      effective softening elements to improve the wetting of aluminum liquid on
      B6Si(s). This approach provides a concept and tool to advance research in
      catalytic chemistry, nucleation (growth), elastowetting, and cell-substrate
      interactions. 

PMID- 25844934
TI  - Natural T Cell-mediated Protection against Seasonal and Pandemic Influenza.
      Results of the Flu Watch Cohort Study.
AB  - RATIONALE: A high proportion of influenza infections are asymptomatic. Animal and
      human challenge studies and observational studies suggest T cells protect against
      disease among those infected, but the impact of T-cell immunity at the population
      level is unknown. OBJECTIVES: To investigate whether naturally preexisting T-cell
      responses targeting highly conserved internal influenza proteins could provide
      cross-protective immunity against pandemic and seasonal influenza. METHODS: We
      quantified influenza A(H3N2) virus-specific T cells in a population cohort during
      seasonal and pandemic periods between 2006 and 2010. Follow-up included paired
      serology, symptom reporting, and polymerase chain reaction (PCR) investigation of
      symptomatic cases. MEASUREMENTS AND MAIN RESULTS: A total of 1,414 unvaccinated
      individuals had baseline T-cell measurements (1,703 participant observation
      sets). T-cell responses to A(H3N2) virus nucleoprotein (NP) dominated and
      strongly cross-reacted with A(H1N1)pdm09 NP (P < 0.001) in participants lacking
      antibody to A(H1N1)pdm09. Comparison of paired preseason and post-season sera
      (1,431 sets) showed 205 (14%) had evidence of infection based on fourfold
      influenza antibody titer rises. The presence of NP-specific T cells before
      exposure to virus correlated with less symptomatic, PCR-positive influenza A
      (overall adjusted odds ratio, 0.27; 95% confidence interval, 0.11-0.68; P =
      0.005, during pandemic [P = 0.047] and seasonal [P = 0.049] periods). Protection
      was independent of baseline antibodies. Influenza-specific T-cell responses were
      detected in 43%, indicating a substantial population impact. CONCLUSIONS:
      Naturally occurring cross-protective T-cell immunity protects against symptomatic
      PCR-confirmed disease in those with evidence of infection and helps to explain
      why many infections do not cause symptoms. Vaccines stimulating T cells may
      provide important cross-protective immunity.

PMID- 25844938
TI  - Triboelectric charging sequence induced by surface functionalization as a method
      to fabricate high performance triboelectric generators.
AB  - Two different materials, apart from each other in a triboelectric series, are
      required to fabricate high performance triboelectric generators (TEGs). Thus, it
      often limits the choices of materials and causes related processing issues for
      TEGs. To address this issue, we report a simple surface functionalization method
      that can effectively change the triboelectric charging sequence of the materials,
      broadening material choices and enhancing the performance of TEGs. Specifically,
      we functionalized the surfaces of the polyethylene terephthalate (PET) films
      either with poly-l-lysine solution or trichloro(1H,1H,2H,2H-perfluorooctyl)
      silane (FOTS). Consequently, the PET surfaces were modified to have different
      triboelectric polarities in a triboelectric series. The TEGs, fabricated using
      this approach, demonstrated the maximum Vopen-circuit (Voc) of ~330 V and Jshort
      circuit (Jsc) of ~270 mA/m(2), respectively, at an applied force of 0.5 MPa.
      Furthermore, the functionalized surfaces of TEGs demonstrated superior stability
      during cyclic measurement over 7200 cycles, maintaining the performance even
      after a month. The approach introduced here is a simple, effective, and cost
      competitive way to fabricate TEGs, which can also be easily adopted for various
      surface patterns and device structures. 

PMID- 25844937
TI  - Use of formalin-fixed paraffin-embedded samples for gene expression studies in
      breast cancer patients.
AB  - To obtain gene expression profiles from samples collected in clinical trials, we
      conducted a pilot study to assess feasibility and estimate sample attrition rates
      when profiling formalin-fixed, paraffin-embedded specimens. Ten matched fresh
      frozen and fixed breast cancer samples were profiled using the Illumina HT-12 and
      Ref-8 chips, respectively. The profiles obtained with Ref 8, were neither
      technically nor biologically reliable since they failed to yield the expected
      separation between estrogen receptor positive and negative samples. With the use
      of Affymetrix HG-U133 2.0 Plus chips on fixed samples and a quantitative
      polymerase chain reaction -based sample pre-assessment step, results were
      satisfactory in terms of biological reliability, despite the low number of
      present calls (M = 21%+/-5). Compared with the Illumina DASL WG platform,
      Affymetrix data showed a wider interquartile range (1.32 vs 0.57, P<2.2 E-16,)
      and larger fold changes. The Affymetrix chips were used to run a pilot study on
      60 fixed breast cancers. By including in the workflow the sample pre-assessment
      steps, 96% of the samples predicted to give good results (44/46), were in fact
      rated as satisfactory from the point of view of technical and biological
      meaningfulness. Our gene expression profiles showed strong agreement with
      immunohistochemistry data, were able to reproduce breast cancer molecular
      subtypes, and allowed the validation of an estrogen receptor status classifier
      derived in frozen samples. The approach is therefore suitable to profile formalin
      fixed paraffin-embedded samples collected in clinical trials, provided that
      quality controls are run both before (sample pre-assessment) and after
      hybridization on the array. 

PMID- 25844939
TI  - Football fan aggression: the importance of low Basal cortisol and a fair referee.
AB  - Fan aggression in football (soccer) is a societal problem that affects many
      countries worldwide. However, to date, most studies use an epidemiological or
      survey approach to explain football fan aggression. This study used a controlled
      laboratory study to advance a model of predictors for fan aggression. To do so,
      football fans (n = 74) saw a match summary in which their favorite team lost
      against their most important rival. Next, we measured levels of aggression with
      the hot sauce paradigm, in which fans were given the opportunity to administer a
      sample of hot sauce that a rival football supporter had to consume. To
      investigate if media exposure had the ability to reduce aggression, before the
      match fans saw a video in which fans of the rival team commented in a neutral,
      negative, or positive manner on their favorite team. Results showed that the
      media exposure did not affect aggression. However, participants displayed high
      levels of aggression and anger after having watched the match. Also, aggression
      was higher in fans with lower basal cortisol levels, which suggests that part of
      the aggression displayed was proactive and related to anti-social behavior.
      Furthermore, aggression was higher when the referee was blamed and aggression was
      lower when the performance of the participants' favorite team was blamed for the
      match result. These results indicate that aggression increased when the match
      result was perceived as unfair. Interventions that aim to reduce football fan
      aggression should give special attention to the perceived fairness of the match
      result. 

PMID- 25844940
TI  - Energy Thresholds of DNA Damage Induced by UV Radiation: An XPS Study.
AB  - This work stresses on damage at the molecular level caused by ultraviolet
      radiation (UV) in the range from 3.5 to 8 eV, deoxyribonucleic acid (DNA) films
      observed by X-ray photoelectron spectroscopy (XPS). Detailed quantitative XPS
      analysis, in which all the amounts are relative to sodium-assumed not to be
      released from the samples, of the carbon, oxygen, and particularly, nitrogen
      components, reveals that irradiation leads to sugar degradation with CO-based
      compounds release for energies above 6.9 eV and decrease of nitrogen groups which
      are not involved in hydrogen bonding at energies above 4.2 eV. Also the phosphate
      groups are seen to decrease to energies above 4.2 eV. Analysis of XPS spectra
      allowed to conclude that the damage on bases peripheral nitrogen atoms are
      following the damage on phosphates. It suggests that very low kinetic energy
      photoelectrons are ejected from the DNA bases, as a result of UV light induced
      breaking of the phosphate ester groups which forms a transient anion with
      resonance formation and whereby most of the nitrogen DNA peripheral groups are
      removed. The degree of ionization of DNA was observed to increase with radiation
      energy, indicating that the ionized phosphate groups are kept unchanged. This
      result was interpreted by the shielding of phosphate groups caused by water
      molecules hydration near sodium atoms. 

PMID- 25844943
TI  - Replacing the elderly with older adults in JGSW publications.

PMID- 25844941
TI  - Behavioral Interventions to Reduce Sexual Risk Behavior in Adults with HIV/AIDS
      Receiving HIV Care: A Systematic Review.
AB  - Regular interactions with people living with HIV/AIDS (PLWHA) who are receiving
      care provide caregivers opportunities to deliver interventions to reduce HIV
      related risks. We conducted a systematic review of behavioral interventions for
      PLWHA (provided at individual level by caregivers at HIV care settings) to
      determine their efficacy in reducing sexual risk behavior. Conference websites
      and biomedical literature databases were searched for studies from 1981 to 2013.
      Randomized and quasi-randomized controlled trials (with standard-of-care control
      groups), considering at least one of a list of HIV-related behavioral or
      biological outcomes in PLWHA aged >=18 receiving HIV care with at least 3-month
      follow-up were included. No language or publication status restrictions were set.
      Standardized search, data abstraction, and evaluation methods were used. Five
      randomized controlled trials were included in the review. We found limited
      evidence that sexual risk reduction interventions increase condom use consistency
      in HIV transmission risk acts, and reduce the number of (casual) sexual partners.
      We still believe that regular interactions between HIV care providers and PLWHA
      provide valuable opportunities for theory-based sexual risk reduction
      interventions to restrain the spread of HIV.

PMID- 25844942
TI  - IFI35, mir-99a and HCV genotype to predict sustained virological response to
      pegylated-interferon plus ribavirin in chronic hepatitis C.
AB  - Although, the treatment of chronic hepatitis C (CHC) greatly improved with the
      use of direct antiviral agents, pegylated-interferon (PEG-IFN) plus ribavirin
      remains an option for many patients, worldwide. The intra-hepatic level of
      expression of interferon stimulated genes (ISGs) and the rs12979860 CC genotype
      located within IFNL3 have been associated with sustained virological response
      (SVR), in patients with CHC. The aim of the study was to identify micro-RNAs
      associated with SVR and to build an accurate signature to predict SVR. Pre
      treatment liver biopsies from 111 patients, treated with PEG-IFN plus ribavirin,
      were studied. Fifty-seven patients had SVR, 36 non-response (NR) and 18 relapse
      (RR). The expression of 851 human miRNAs and 30 selected mRNAs, including ISGs,
      was assessed by RT-qPCR. In the first group of patients (screen), 20 miRNAs out
      of the 851 studied were deregulated between NRs and SVRs. From the 4 miRNAs
      validated (mir-23a, mir-181a*, mir-217 and mir-99a), in the second group of
      patients (validation), 3 (mir-23a, mir-181a* and mir-99a) were down-regulated in
      NRs as compared to SVRs. The ISGs, studied, were accumulated in SVRs and IFNL3
      rs12979860 CT/TT carriers compared respectively to NRs and CC carriers.
      Combining, clinical data together with the expression of selected genes and micro
      RNAs, we identified a signature (IFI35, mir-99a and HCV genotype) to predict SVR
      (AUC:0.876) with a positive predictive value of 86.54% with high sensibility
      (80%) and specificity (80.4%). This signature may help to characterize patients
      with low chance to respond to PEG-IFN/ribavirin and to elucidate mechanisms of
      NR. 

PMID- 25844944
TI  - Induction and Repair of DNA DSB as Revealed by H2AX Phosphorylation Foci in Human
      Fibroblasts Exposed to Low- and High-LET Radiation: Relationship with Early and
      Delayed Reproductive Cell Death.
AB  - The spatial distribution of radiation-induced DNA breaks within the cell nucleus
      depends on radiation quality in terms of energy deposition pattern. It is
      generally assumed that the higher the radiation linear energy transfer (LET), the
      greater the DNA damage complexity. Using a combined experimental and theoretical
      approach, we examined the phosphorylation-dephosphorylation kinetics of radiation
      induced gamma-H2AX foci, size distribution and 3D focus morphology, and the
      relationship between DNA damage and cellular end points (i.e., cell killing and
      lethal mutations) after exposure to gamma rays, protons, carbon ions and alpha
      particles. Our results showed that the maximum number of foci are reached 30 min
      postirradiation for all radiation types. However, the number of foci after 0.5 Gy
      of each radiation type was different with gamma rays, protons, carbon ions and
      alpha particles inducing 12.64 +/- 0.25, 10.11 +/- 0.40, 8.84 +/- 0.56 and 4.80
      +/- 0.35 foci, respectively, which indicated a clear influence of the track
      structure and fluence on the numbers of foci induced after a dose of 0.5 Gy for
      each radiation type. The gamma-H2AX foci persistence was also dependent on
      radiation quality, i.e., the higher the LET, the longer the foci persisted in the
      cell nucleus. The gamma-H2AX time course was compared with cell killing and
      lethal mutation and the results highlighted a correlation between cellular end
      points and the duration of gamma-H2AX foci persistence. A model was developed to
      evaluate the probability that multiple DSBs reside in the same gamma-ray focus
      and such probability was found to be negligible for doses lower than 1 Gy. Our
      model provides evidence that the DSBs inside complex foci, such as those induced
      by alpha particles, are not processed independently or with the same time
      constant. The combination of experimental, theoretical and simulation data
      supports the hypothesis of an interdependent processing of closely associated
      DSBs, possibly associated with a diminished correct repair capability, which
      affects cell killing and lethal mutation. 

PMID- 25844945
TI  - Analyses of ionizing radiation effects in vitro in peripheral blood lymphocytes
      with Raman spectroscopy.
AB  - The use of Raman spectroscopy to measure the biochemical profile of healthy and
      diseased cells and tissues may be a potential solution to many diagnostic
      problems in the clinic. Although extensively used to identify changes in the
      biochemical profiles of cancerous cells and tissue, Raman spectroscopy has been
      used less often for analyzing changes to the cellular environment by external
      factors such as ionizing radiation. In tandem with this, the biological impact of
      low doses of ionizing radiation remains poorly understood. Extensive studies have
      been performed on the radiobiological effects associated with radiation doses
      above 0.1 Gy, and are well characterized, but recent studies on low-dose
      radiation exposure have revealed complex and highly variable responses. We report
      here the novel finding that demonstrate the capability of Raman spectroscopy to
      detect radiation-induced damage responses in isolated lymphocytes irradiated with
      doses of 0.05 and 0.5 Gy. Lymphocytes were isolated from peripheral blood in a
      cohort of volunteers, cultured ex vivo and then irradiated. Within 1 h after
      irradiation spectral effects were observed with Raman microspectroscopy and
      principal component analysis and linear discriminant analysis at both doses
      relative to the sham-irradiated control (0 Gy). Cellular DNA damage was confirmed
      using parallel gamma-H2AX fluorescence measurements on the extracted lymphocytes
      per donor and per dose. DNA damage measurements exhibited interindividual
      variability among both donors and dose, which matched that seen in the spectral
      variability in the lymphocyte cohort. Further evidence of links between spectral
      features and DNA damage was also observed, which may potentially allow
      noninvasive insight into the DNA remodeling that occurs after exposure to
      ionizing radiation. 

PMID- 25844946
TI  - Biodosimetry Based on gamma-H2AX Quantification and Cytogenetics after Partial-
      and Total-Body Irradiation during Fractionated Radiotherapy.
AB  - The aim of this current study was to quantitatively describe radiation-induced
      DNA damage and its distribution in leukocytes of cancer patients after
      fractionated partial- or total-body radiotherapy. Specifically, the impact of
      exposed anatomic region and administered dose was investigated in breast and
      prostate cancer patients receiving partial-body radiotherapy. DNA double-strand
      breaks (DSBs) were quantified by gamma-H2AX immunostaining. The frequency of
      unstable chromosomal aberrations in stimulated lymphocytes was also determined
      and compared with the frequency of DNA DSBs in the same samples. The frequency of
      radiation-induced DNA damage was converted into dose, using ex vivo generated
      calibration curves, and was then compared with the administered physical dose.
      This study showed that 0.5 h after partial-body radiotherapy the quantity of
      radiation-induced gamma-H2AX foci increased linearly with the administered
      equivalent whole-body dose for both tumor entities. Foci frequencies dropped 1
      day thereafter but proportionality to the equivalent whole-body dose was
      maintained. Conversely, the frequency of radiation-induced cytogenetic damage
      increased from 0.5 h to 1 day after the first partial-body exposure with a linear
      dependence on the administered equivalent whole-body dose, for prostate cancer
      patients only. Only gamma-H2AX foci assessment immediately after partial-body
      radiotherapy was a reliable measure of the expected equivalent whole-body dose.
      Local tumor doses could be approximated with both assays after one day. After
      total-body radiotherapy satisfactory dose estimates were achieved with both
      assays up to 8 h after exposure. In conclusion, the quantification of radiation
      induced gamma-H2AX foci, but not cytogenetic damage in peripheral leukocytes was
      a sensitive and rapid biodosimeter after acute heterogeneous irradiation of
      partial body volumes that was able to primarily assess the absorbed equivalent
      whole-body dose. 

PMID- 25844947
TI  - In memoriam: Arthur C. Upton (1923-2015).

PMID- 25844948
TI  - Connecting radiation-induced bystander effects and senescence to improve
      radiation response prediction.
AB  - For the last two decades radiation-induced bystander effects (RIBEs) have
      attracted significant attention due to their possible implications for
      radiotherapy. However, despite extensive research, the molecular pathways
      associated with RIBEs are still not completely known. In the current study we
      investigated the role of senescence in the bystander response. Irradiated (2, 4,
      6 and 8 Gy) human colorectal carcinoma cells (HCT116) with p53(+/+) (wild-type)
      or p53(-/-) (knockout) gene were co-incubated with nonirradiated cells of the
      same type. Clonogenic and senescence assays were used for both irradiated and co
      incubated bystander cell populations. We also performed additional measurements
      on the number of remaining cells after the whole co-incubation period. For
      radiation doses larger than 2 Gy we observed much larger fractions of senescent
      cells in p53-positive populations compared to their p53-negative counterparts
      (15.81% vs. 3.63% in the irradiated population; 2.89% vs. 1.05% in the bystander
      population; 8 Gy; P < 0.05). Statistically significant differences between cell
      lines in the clonogenic cell surviving fraction were observed for doses higher
      than 4 Gy (1.61% for p53(+/+) vs. 0.19% for p53(-/-) in irradiated population;
      3.57% for +/+ vs. 50.39% for -/- in bystander population; 8 Gy; P < 0.05). Our
      main finding was that the number of senescent cells in the irradiated population
      correlated strongly with the clonogenic cell surviving fraction (R = -0.98, P <
      0.001) and the number of senescent cells (R = 0.97, P < 0.001) in the bystander
      population. We also extended the standard linear-quadratic radiation response
      model by incorporating the influence of the signals released by the senescent
      cells, which accurately described the radiation response in the bystander
      population. Our findings suggest that radiation-induced senescence might be a key
      player in RIBE, i.e., the strength of RIBE depends on the amount of radiation
      induced senescence. 

PMID- 25844949
TI  - The development and manufacture of influenza vaccines.
AB  - The development and manufacture of an Influenza vaccine is unlike any other
      product in the Vaccine industry because of the need to change composition on a
      yearly basis. The poor efficacy of Influenza vaccines over the past 2 y in the
      Northern Hemisphere invites questions on how the vaccines are manufactured and
      how change in vaccine composition is controlled. The opinion expressed in this
      commentary is that the risk of not making the correct HA protein is increased by
      the need to adapt the new seasonal virus for good propagation in embryonated
      chicken eggs. This adaptation is required because not enough doses can be made in
      time for the new 'flu season unless productivity is reasonable. This problem is
      not necessarily solved by going to a cell culture host for virus propagation and
      that may explain why this more advanced technology approach is not more widely
      used. A vaccine based on hemagglutinin (HA) protein that does not involve
      Influenza virus propagation (such as Flublok(r)) side steps this particular
      problem. The exact HA sequence can be used as is in the virus. The technology can
      be run at large scale, already at 2 * 21,000L in Japan, in contrast to eggs where
      scale-up is by multiplication; the HA product is highly purified and made
      consistently in the form of rosettes. 

PMID- 25844950
TI  - An Apparatus to Deliver Mannitol Powder for Bronchial Provocation in Children
      Under Six Years Old.
AB  - BACKGROUND: Currently bronchial provocation testing (BPT) using mannitol powder
      cannot be performed in children under 6 years. A primary reason is it is
      challenging for children at this age to generate a consistent inspiratory effort
      to inhale mannitol efficiently from a dry powder inhaler. A prototype system,
      which does not require any inhalation training from the pediatric subject, is
      reported here. It uses an external source of compressed air to disperse mannitol
      powder into a commercial holding chamber. Then the subject uses tidal breathing
      to inhale the aerosol. METHOD: The setup consists of a commercially available
      powder disperser and VolumaticTM holding chamber. Taguchi experimental design was
      used to identify the effect of dispersion parameters (flow rate of compressed
      air, time compressed air is applied, mass of powder, and the time between
      dispersion and inhalation) on the fine particle dose (FPD). The prototype was
      tested in vitro using a USP throat connected to a next generation impactor. The
      aerosols from the holding chamber were drawn at 10 L/min. A scaling factor for
      estimating the provoking dose to induce a 15% reduction in forced expiratory
      volume in 1 second (FEV1) (PD15) was calculated using anatomical dimensions of
      the human respiratory tract at various ages combined with known dosing values
      from the adult BPT. RESULTS: Consistent and doubling FPDs were successfully
      generated based on the Taguchi experimental design. The FPD was reliable over a
      range of 0.8 (+/-0.09) mg to 14 (+/-0.94) mg. The calculated PD15 for children
      aged 1-6 years ranged from 7.1-30 mg. The FPDs generated from the proposed set up
      are lower than the calculated PD15 and therefore are not expected to cause sudden
      bronchoconstriction. CONCLUSION: A prototype aerosol delivery system has been
      developed that is consistently able to deliver doubling doses suitable for
      bronchial provocation testing in young children.

PMID- 25844951
TI  - Risk Factors for Abdominal Incision Infection after Colorectal Surgery in a Saudi
      Arabian Population: The Method of Surveillance Matters.
AB  - BACKGROUND: Reported surgical site infection rates range from 2.1% to 40% after
      colorectal surgery and are believed to be underestimated depending on the method
      of surveillance. The study aims were to identify an accurate incidence and
      associated risk factors for abdominal incision surgical site infection after
      elective open colorectal surgery in a Saudi population. METHODS: This was a
      prospective observational longitudinal study of 300 consecutive adult patients,
      recruited upon admission to an 800-bed tertiary referral center. All consenting
      adults admitted for elective open colorectal surgery were included. Patients were
      followed for 36 d post-surgery by two certified and experienced wound care
      experts who diagnosed abdominal incision surgical site infections. The definition
      provided by the U.S. Centers for Disease Control and Prevention was used.
      Statistical analysis was performed using both univariate and multivariable
      logistic regression. RESULTS: Data were analyzed for 296 patients; the incidence
      of abdominal surgical site infection was 30%. Factors associated with surgical
      site infection by univariate analysis were pre-operative pre-albumin (p=0.04,
      odds ratio [OR] 0.81, 95% confidence interval [CI] 0.66-0.99); operative
      difficulty because of truncal obesity (p=0.006, OR 2.19, 95% CI 1.25-3.84) and
      obesity measured by body mass index (p=0.002, OR 4.00, 95% CI 1.95-8.20).
      Multivariable analysis identified only two significant risk factors: Pre
      operative pre-albumin (p=0.02, OR 0.76, 95% CI 0.60-0.96), and obesity measured
      by body mass index (BMI; p=0.001, OR 4.71, 95% CI 2.20-10.10). CONCLUSION:
      Obesity and nutritional status correlated with post-operative abdominal surgical
      site infection. The method of surveillance and length of follow-up impact the
      rate reported.

PMID- 25844952
TI  - Differentiation Between the Potential Subdural Space and Subarachnoid Space Was
      Difficult With Fluoroscopy Due to Obesity.

PMID- 25844953
TI  - Dexmedetomidine Attenuates Neurotoxicity Induced by Prenatal Propofol Exposure.
AB  - BACKGROUND: Anesthetic agents (eg, isoflurane, propofol) may cause
      neurodegeneration in the developing brains and impair animals' learning ability.
      Dexmedetomidine (DEX), a selective alpha 2-adrenoreceptor agonist, has
      antiapoptotic properties in several brain injury models. Here, we tested whether
      DEX can protect the brain from neurodegeneration in rats exposed to propofol in
      utero. MATERIALS AND METHODS: Fetal rats of embryonic day 20 were exposed in
      utero for 1 hour to propofol anesthesia with DEX or saline, or no anesthesia
      (control). The fetal brains were harvested 6 hours later. Cleaved caspase-3
      levels and the relative number of ionized calcium-binding adaptor molecule 1
      (IBA1)-positive cells were assessed by Western blot and immunohistochemistry.
      Learning and memory functions of the offspring in a separate cohort were assessed
      at postnatal day 35 by using an 8-arm radial maze. RESULTS: Propofol anesthesia
      in pregnant rats augmented caspase-3 activation by 217% in the brain tissues of
      fetal rats and increased the number of IBA1-positive cells in the cortex by 40%
      and in the thalamus by 270%. Juvenile rats exposed prenatally to propofol were
      not different than controls on spontaneous locomotor activity, but made more
      errors of omission and took longer to complete visiting all 8 arms on days 1, 2,
      and 3 across a 5-day test in the radial arm maze. This neurocognitive deficit was
      prevented by administration of DEX (5.0 ug/kg, IP), which also significantly
      inhibited propofol-induced caspase-3 activation and microglial response in the
      fetal brains. CONCLUSIONS: DEX attenuates neuronal injury induced by maternal
      propofol anesthesia in the fetal brains, providing neurocognitive protection in
      the offspring rats.

PMID- 25844954
TI  - A Case of Nephrogenic Diabetes Insipidus During Transsphenoidal Pituitary
      Adenomectomy.

PMID- 25844955
TI  - A Universal Aptamer Chimera for the Delivery of Functional microRNA-126.
AB  - microRNAs (miRs) regulate vascular diseases such as atherosclerosis and cancer.
      miR-126 is important for endothelial cell signaling and promotes angiogenesis,
      protects against atherosclerosis, and reduces breast cancer cell growth and
      metastasis. The overexpression of miR-126, therefore, may be an attractive
      therapeutic strategy for the treatment of cardiovascular disease or cancer. Here
      we report a novel strategy to deliver miR-126 to endothelial and breast cancer
      cells. We tested three different strategies to deliver miR-126 by linking the miR
      to an aptamer for the ubiquitously expressed transferrin receptor (transferrin
      receptor aptamer, TRA). Linking the precursor of miR-126 (pre-miR-126) to the TRA
      by annealing of a complementary stick led to efficient uptake and processing of
      miR-126, resulting in the delivery of 1.6*10(6)+/-0.3*10(6) copies miR-126-3p per
      ng RNA in human endothelial cells and 7.4*10(5)+/-2*10(5) copies miR-126-3p per
      ng in MCF7 breast cancer cells. The functionality of the active TRA-miR-126
      chimera was further demonstrated by showing that the chimera represses the known
      miR-126 target VCAM-1 and improved endothelial cell sprouting in a spheroid
      assay. Moreover, the TRA-miR-126 chimera reduced proliferation and paracrine
      endothelial cell recruitment of breast cancer cells to a similar extent as miR
      126-3p mimics introduced by conventional liposome-based transfection. Together,
      this data demonstrates that pre-miR-126 can be delivered by a non-specific
      aptamer to exert biological functions in two different cell models. The use of
      the TRA-miR-126 chimera or the combination of the delivery strategy with other
      endothelial or tumor specific aptamers may provide an interesting therapeutic
      option to treat vascular disease or cancers. 

PMID- 25844957
TI  - Mechanical Strain Induced Tunable Anisotropic Wetting on Buckled PDMS Silver
      Nanorods Arrays.
AB  - We report the fabrication of anisotropic superhydrophobic surface with dual-scale
      roughness by the deposition of silver nanorods arrays on prestretched
      poly(dimethylsiloxane) (PDMS) using oblique angle deposition and subsequent
      release of strain after the deposition, which resulted in the formation of
      microbuckles/wrinkles. The amplitude and periodicity of the wrinkles were tuned
      by varying the prestretching mechanical strain (epsilon) applied to the PDMS film
      from 0 to 30% prior to Ag nanorods deposition. The peaks and valleys in the
      surface topography of Ag nanorods arrays covered PDMS films lead to anisotropic
      wetting by water droplet. The droplet is free to move along the direction
      parallel to the wrinkles, but the droplet moving perpendicular to the wrinkles
      confront energy barrier leading to wetting anisotropy. The anisotropic
      wettability was tuned from 22 to 37 degrees  for 10-30% prestretched PDMS film.
      The dual scale roughness (nanorods on micro wrinkles) was found to be responsible
      for the superhydrophobicity (contact angle ~155 degrees ) of the sample prepared
      for 30% prestretched PDMS film in perpendicular direction. The wetting behavior
      of the Ag nanorods PDMS film surface was reversibly tuned by applying the
      mechanical strain, which induces the change in the microscale roughness
      determined by amplitude (A) and periodicity (lambda) of the buckles. Most
      interestingly, the water droplet also displayed the anisotropy in the roll-off
      angle. The effect of different A and lambda on anisotropic wettability of Ag
      nanorods arrays/PDMS film was also demonstrated by lattice Boltzmann (LB)
      modeling. These findings may produce a promising way of controlling the direction
      of liquid flow such as in microfluidic devices and transportation of the
      microliter water droplets in a preset direction. 

PMID- 25844958
TI  - Presentation and progression of childhood-onset inflammatory bowel disease in
      Northern Stockholm County.
AB  - BACKGROUND: Some studies have suggested that childhood-onset inflammatory bowel
      disease (IBD) is characterized by extensive intestinal involvement and rapid
      progression to complications. Here, we report the presentation and progression of
      patients diagnosed with IBD during childhood in a population-based cohort from
      northern Stockholm County. METHODS: Medical records for all 280 patients
      diagnosed in the period 1990-2007 with childhood-onset IBD in northern Stockholm
      County were followed until 2011 (median follow-up time, 8.8 yr). Disease
      phenotypes were classified according to the Paris pediatric IBD classification.
      RESULTS: Among the 74 patients with ulcerative colitis, 72% presented with
      pancolitis. Among the 200 patients with Crohn's disease (CD), 75% presented with
      colitis. Complicated disease behavior was observed in 18% of patients with CD by
      end of follow-up. Extension of the disease territory was observed in 22% of
      patients with ulcerative colitis and 15% of patients with CD. The cumulative risk
      of intra-abdominal surgery after 10 years was 8% (95% confidence interval, 4%
      20%) for ulcerative colitis and 22% (95% confidence interval, 15%-28%) for
      patients with CD. Nonmucosal healing at 1 year was associated with a complicated
      disease course in patients with CD (hazard ratio = 14.56; 95% confidence
      interval, 1.79-118.68; P = 0.01). CONCLUSIONS: Patients with childhood-onset IBD
      were characterized by extensive colitis that was relatively stable over time and
      associated with a relatively low risk of complications and abdominal surgery. Our
      findings confirm the more extensive disease location in pediatric IBD but did not
      identify the proposed dynamic and aggressive nature of the childhood-onset
      phenotype. The association of nonmucosal healing with a complicated disease
      course suggests that endoscopy should guide treatment intensity in childhood
      onset CD.

PMID- 25844960
TI  - MicroRNAs in inflammatory bowel diseases: paradoxes and possibilities.
AB  - MicroRNAs (miRNAs) are single-stranded RNA molecules, which influence the
      translation of messenger RNA and hence protein synthesis. The altered expression
      of miRNAs in disease states in cancer and autoimmune diseases including
      inflammatory bowel disease is providing new insights into disease pathogenesis.
      This understanding is leading to consideration of the utility of miRNAs in
      diagnostics, prognostics, and therapeutics in inflammatory bowel disease. A
      literature search was conducted using the MEDLINE/PubMed databases using search
      terms inflammatory bowel disease, miRNA, treatment, and biomarkers. 

PMID- 25844959
TI  - Recent advances in characterizing the gastrointestinal microbiome in Crohn's
      disease: a systematic review.
AB  - BACKGROUND: The intestinal microbiota is involved in the pathogenesis of
      inflammatory bowel disease. A reduction in the diversity of the intestinal
      microbiota as well as specific taxonomic and functional shifts have been reported
      in Crohn's disease and may play a central role in the inflammatory process. The
      aim was to systematically review recent developments in the structural and
      functional changes observed in the gastrointestinal microbiome in patients with
      Crohn's Disease. RESULTS: Seventy-two abstracts were included in this review. The
      effects of host genetics, disease phenotype, and inflammatory bowel disease
      treatment on the gastrointestinal microbiome in Crohn's disease were reviewed,
      and taxonomic shifts in patients with early and established disease were
      described. The relative abundance of Bacteroidetes is increased and Firmicutes
      decreased in Crohn's disease compared with healthy controls. Enterobacteriaceae,
      specifically Eschericia coli, is enriched in Crohn's disease. Faecalibacterium
      prausnitzii is found at lower abundance in Crohn's disease and in those with
      postoperative recurrence. Observed functional changes include major shifts in
      oxidative stress pathways, a decrease in butanoate and propanoate metabolism gene
      expression, lower levels of butyrate, and other short-chain fatty acids,
      decreased carbohydrate metabolism, and decreased amino acid biosynthesis.
      CONCLUSIONS: Changes in microbial composition and function have been described,
      although a causative role remains to be established. Larger, prospective, and
      longitudinal studies are required with deep interrogation of the microbiome if
      causality is to be determined, and refined microbial manipulation is to emerge as
      a focused therapy.

PMID- 25844961
TI  - Endogenous levels of circulating androgens and risk of Crohn's disease and
      ulcerative colitis among women: a nested case-control study from the nurses'
      health study cohorts.
AB  - BACKGROUND: Androgens, which are known to be altered by exogenous hormone use,
      have recently been linked to alterations of the gut microbiome and mucosal immune
      function. No study has evaluated the association between circulating levels of
      androgens and risk of Crohn's disease (CD) and ulcerative colitis (UC). METHODS:
      We conducted a nested case-control study of women enrolled in the Nurses' Health
      Study and Nurses' Health Study II who provided a blood specimen. Cases of CD and
      UC were each matched to 2 controls. Prediagnosis plasma levels of
      dehydroepiandrosterone sulfate, testosterone, and sex hormone-binding globulin
      were measured. We examined the association of each analyte with risk of CD or UC
      using conditional logistic regression models. RESULTS: Compared with women in the
      lowest quintile of testosterone, the multivariable-adjusted odds ratios for CD
      were 0.86 (95% confidence interval, 0.39-1.90) for women in the second quintile,
      0.49 (95% confidence interval, 0.21-1.15) for the third quartile, 0.22 (0.08
      0.65) for the fourth quintile, and 0.39 (95% confidence interval, 0.16-0.99) for
      the highest quintile (Plinear trend = 0.004). In contrast, we did not observe a
      consistent association between prediagnostic testosterone and risk of UC (Plinear
      trend = 0.84). We also did not observe any association between plasma levels of
      sex hormone-binding globulin or dehydroepiandrosterone sulfate and risk of UC or
      CD (all Plinear trends > 0.10). CONCLUSIONS: Among women, prediagnostic
      circulating testosterone is associated with a lower risk of CD but not UC.
      Further studies to understand the biological mechanisms by which endogenous
      androgens may mediate the etiopathogenesis of CD are warranted.

PMID- 25844962
TI  - Iron Replacement in Patients with Inflammatory Bowel Disease: A Systematic Review
      and Meta-analysis.
AB  - BACKGROUND: A number of controlled trials and prospective studies have compared
      intravenous (IV) to oral (PO) iron for the treatment of iron deficiency anemia
      with mixed results. METHODS: We conducted a systematic review of trials published
      on 2014 that compared IV with PO iron to treat in patients with IBD. Meta
      analysis was performed to generate effect estimates. Quality assessment was also
      performed according to GRADE criteria. RESULTS: Five studies met our inclusion
      criteria, enrolling 694 patients. For the primary outcome of "response"
      (hemoglobin rise >2 g/dL), there was no significant difference between IV or PO
      iron; risk ratio for response with IV was 1.08 (95% CI, 0.9-1.2; P = 0.2). For
      the secondary outcome of mean change in hemoglobin (g/dL), the mean difference
      between PO and IV iron was not statistically significant (mean difference, 0.6
      g/dL, 96% CI, -0.1 to 1.3; P = 0.08). IV iron was associated with a significantly
      greater initial rise in serum ferritin compared with PO iron (mean difference 89
      ng/mL; 95% CI, 29-148, P = 0.003). There was a lower risk of withdrawal due to
      adverse events in these trials in the IV iron cohorts when compared with PO iron
      (risk ratio, 0.4; 95% CI, 0.1-1.0; P = 0.05). CONCLUSIONS: We found no
      significant difference between IV and PO iron in correcting iron-deficiency
      anemia in patients with IBD in this meta-analysis. Patients who received IV iron
      had a greater rise in serum ferritin and were less likely to stop treatment due
      to adverse events, when compared with those who received PO iron.

PMID- 25844963
TI  - Vedolizumab for induction and maintenance of remission in ulcerative colitis: a
      Cochrane systematic review and meta-analysis.
AB  - BACKGROUND: We performed a systematic review to evaluate the efficacy and safety
      of vedolizumab for induction and maintenance of remission in ulcerative colitis.
      METHODS: A literature search to June 2014 identified all applicable randomized
      trials. Outcome measures were clinical and endoscopic remission, clinical and
      endoscopic response, quality of life, and adverse events. The risk ratio (RR) and
      95% confidence intervals (CI) were estimated for each outcome. Study quality was
      evaluated using the Cochrane risk of bias tool. The GRADE criteria were used to
      assess the quality of the evidence. MAIN RESULTS: Four studies (606 patients)
      were included. The risk of bias was low. Pooled analyses indicated that
      vedolizumab was significantly superior to placebo for induction of remission (RR
      = 0.86, 95% CI, 0.80-0.91), clinical response (RR = 0.82, 95% CI, 0.75-0.91),
      endoscopic remission (RR = 0.82, 95% CI, 0.75-0.91), and for achieving remission
      at 52 weeks in week 6 responders (RR = 2.73, 95% CI, 1.78-4.18). GRADE analyses
      suggested that the overall quality of the evidence was high for induction of
      remission and moderate for maintenance therapy (due to sparse data consisting of
      246 events). No statistically significant difference was observed in the
      incidence of adverse events between vedolizumab and placebo. CONCLUSIONS:
      Vedolizumab is superior to placebo as induction and maintenance therapy for
      ulcerative colitis. Future studies are needed to define long-term efficacy and
      safety of this agent.

PMID- 25844964
TI  - gamma-Tocotrienol-induced endoplasmic reticulum stress and autophagy act
      concurrently to promote breast cancer cell death.
AB  - The anticancer effects of gamma-tocotrienol are associated with the induction of
      autophagy and endoplasmic reticulum (ER) stress-mediated apoptosis, but a direct
      relationship between these events has not been established. Treatment with 40
      MUmol/L of gamma-tocotrienol caused a time-dependent decrease in cancer cell
      viability that corresponds to a concurrent increase in autophagic and endoplasmic
      reticulum (ER) stress markers in MCF-7 and MDA-MB-231 human breast cancer cells.
      gamma-Tocotrienol treatment was found to cause a time-dependent increase in early
      phase (Beclin-1, LC3B-II) and late phase (LAMP-1 and cathepsin-D) autophagy
      markers, and pretreatment with autophagy inhibitors Beclin-1 siRNA, 3-MA or Baf1
      blocked these effects. Furthermore, blockage of gamma-tocotrienol-induced
      autophagy with Beclin-1 siRNA, 3-MA, or Baf1 induced a modest, but significant,
      reduction in gamma-tocotrienol-induced cytotoxicity. gamma-Tocotrienol treatment
      was also found to cause a decrease in mitogenic Erk1/2 signaling, an increase in
      stress-dependent p38 and JNK1/2 signaling, as well as an increase in ER stress
      apoptotic markers, including phospho-PERK, phospho-eIF2alpha, Bip, IRE1alpha, ATF
      4, CHOP, and TRB3. In summary, these finding demonstrate that gamma-tocotrienol
      induced ER stress and autophagy occur concurrently, and together act to promote
      human breast cancer cell death. 

PMID- 25844965
TI  - Synovial heterogeneity in rheumatoid arthritis: the key for rational patient
      stratification?

PMID- 25844966
TI  - Balancing the benefits and risks of low-dose glucocorticoid in rheumatoid
      arthritis.
AB  - Glucocorticoids have potent anti-inflammatory and immunomodulatory effects and
      are widely use in the management of rheumatoid arthritis in combination with
      other synthetic and with biological disease-modifying anti-rheumatic drugs.
      Concerns about the risk of adverse effects of glucocorticoids, especially if they
      are given at higher dosages and for a longer time, hamper their use despite the
      clear symptomatic and disease modifying benefits. However, the evidence base for
      these concerns for low dose glucocorticoid therapy is quite limited due to the
      scarcity of quality literature on its safety in rheumatoid arthritis. This review
      discusses the current understanding about their disease-modifying effects,
      toxicity data from recent trials and observational studies, recommendations for
      their management and the current efforts to improve the therapeutic ratio of
      glucocorticoid through the development of new formulations, such as modified
      release prednisone.

PMID- 25844967
TI  - Depressive symptoms are independently associated with pain perception in
      Colombians with rheumatoid arthritis.
AB  - AIMS: To examine the relationships between psychosocial factors and reported pain
      in Colombians with Rheumatoid Arthritis (RA). METHODS: One hundred and three RA
      patients [85% from the lowest socio-economic strata (SES) in the country]
      recruited from outpatient centers in Neiva, Colombia were administered the
      Disease Activity Scale (DAS) , which included a Visual Analog Scale (VAS)
      arthritis pain/activity rating, Zung Depression Scale, State-Trait Anxiety
      Inventory (STAI), Interpersonal Support Evaluation List-12 (ISEL-12), and Symptom
      Checklist-90 Revised (SCL-90R). MAJOR RESULTS: VAS pain was not associated with
      socio-demographic or medical factors, but was negatively associated with ISEL
      tangible subscale (r=-0.22, p< 0.01; r=0.28, p<0.01). VAS pain was positively
      associated with Zung Depression Scale score (r=0.38, p<0.001), STAI-State and
      STAI-Trait Anxiety (r=0.23 and r=0.25 respectively, p's<0.01), SCL-90R Global
      Severity Index (GSI) and Positive Symptom Total (PST) (r=0.23, p<0.05 and r=0.29,
      p<0.01 respectively), and SCL-90R Somatization, Depression, and Anxiety subscales
      (r=0.30, p< 0.01; r=0.28, p<0.01; and r=0.20, p<0.05 respectively). A linear
      regression model showed that socio-demographic characteristics theoretically
      associated with pain perception (gender, age, and SES) explained only 2.4% of the
      variance of VAS scores (R(2)=0.02, p=0.49). The full model, including
      psychosocial factors significantly associated with VAS scores explained 18.9% of
      the variance in VAS pain perception scores (R(2)=0.19, p=0.02). The Zung
      Depression Scale score was the only factor independently associated with VAS
      pain, such that higher depression scores were associated with higher VAS ratings
      (beta =0.13, p<0.01), controlling for gender, age, SES, STAI-State, STAI-Trait,
      ISEL tangible, SCL-90R GSI, and SCL-90R PST. CONCLUSIONS: Depressive symptoms,
      anxiety, social support, and psychopathological symptom distress were associated
      with pain ratings, but only depressive symptoms were found to be uniquely
      associated with higher pain perception, taking into account socio-demographic
      characteristics and other psychosocial factors. Findings provide evidence for the
      need to assess and treat pain in RA in Colombia from a bio-psycho-social
      perspective. Future research is needed to determine effective depression
      screening and evidence-based interventions for depressive symptoms in RA patients
      in this socio-cultural context, as intervening in depression may decrease pain
      perception.

PMID- 25844968
TI  - Impact of bariatric surgery on life expectancy in severely obese patients with
      diabetes: a decision analysis.
AB  - OBJECTIVE: To create a decision analytic model to estimate the balance between
      treatment risks and benefits for severely obese patients with diabetes.
      BACKGROUND: Bariatric surgery leads to many desirable metabolic changes, but long
      term impact of bariatric surgery on life expectancy in patients with diabetes has
      not yet been quantified. METHODS: We developed a Markov state transition model
      with multiple Cox proportional hazards models and logistic regression models as
      inputs to compare bariatric surgery versus no surgical treatment for severely
      obese diabetic patients. The model is informed by data from 3 large cohorts: (1)
      159,000 severely obese diabetic patients (4185 had bariatric surgery) from 3 HMO
      Research Network sites; (2) 23,000 subjects from the Nationwide Inpatient Sample;
      and (3) 18,000 subjects from the National Health Interview Survey linked to the
      National Death Index. RESULTS: In our main analyses, we found that a 45-year-old
      woman with diabetes and a body mass index (BMI) of 45 kg/m gained an additional
      6.7 years of life expectancy with bariatric surgery (38.4 years with surgery vs
      31.7 years without surgery). Sensitivity analyses revealed that the gain in life
      expectancy decreased with increasing BMI, until a BMI of 62 kg/m is reached, at
      which point nonsurgical treatment was associated with greater life expectancy.
      Similar results were seen for both men and women in all age groups. CONCLUSIONS:
      For most severely obese patients with diabetes, bariatric surgery seems to
      improve life expectancy; however, surgery may reduce life expectancy for the
      super obese with BMIs over 62 kg/m.

PMID- 25844969
TI  - Reliability of surgeon-specific reporting of complications after colectomy.
AB  - OBJECTIVE: We sought to determine the reliability of surgeon-specific
      postoperative complication rates after colectomy. BACKGROUND: Conventional
      measures of surgeon-specific performance fail to acknowledge variation attributed
      to statistical noise, risking unreliable assessment of quality. METHODS: We
      examined all patients who underwent segmental colectomy with anastomosis from
      2008 through 2010 participating in the Michigan Surgical Quality Collaborative
      Colectomy Project. Surgeon-specific complication rates were risk-adjusted
      according to patient characteristics with multiple logistic regression.
      Hierarchical modeling techniques were used to determine the reliability of
      surgeon-specific risk-adjusted complication rates. We then adjusted these rates
      for reliability. To evaluate the extent to which surgeon-level variation was
      reduced, surgeons were placed into quartiles based on performance and
      complication rates were compared before and after reliability adjustment.
      RESULTS: A total of 5033 patients (n = 345 surgeons) undergoing partial colectomy
      reported a risk-adjusted complication rate of 24.5%. Approximately 86% of the
      variability of complication rates across surgeons was explained by measurement
      noise, whereas the remaining 14% represented true signal. Risk-adjusted
      complication rates varied from 0% to 55.1% across quartiles before adjusting for
      reliability. Reliability adjustment greatly diminished this variation, generating
      a 1.2-fold difference (21.4%-25.6%). A caseload of 168 colectomies across 3 years
      was required to achieve a reliability of more than 0.7, which is considered a
      proficient level. Only 1 surgeon surpassed this volume threshold. CONCLUSIONS:
      The vast majority of surgeons do not perform enough colectomies to generate a
      reliable surgeon-specific complication rate. Risk-adjusted complication rates
      should be viewed with caution when evaluating surgeons with low operative volume,
      as statistical noise is a large determinant in estimating their surgeon-specific
      complication rates.

PMID- 25844970
TI  - Robotic-assisted transanal total mesorectal excision: the key against the
      Achilles' heel of rectal cancer?

PMID- 25844971
TI  - Reply to letter: "meta-analyses, from GIGO to PRISMA".

PMID- 25844972
TI  - Reply to letter: "a systematic review of economic evaluations of enhanced
      recovery pathways for colorectal surgery".

PMID- 25844974
TI  - Emotional inertia and external events: The roles of exposure, reactivity, and
      recovery.
AB  - Increased moment-to-moment predictability, or inertia, of negative affect has
      been identified as an important dynamic marker of psychological maladjustment,
      and increased vulnerability to depression in particular. However, little is known
      about the processes underlying emotional inertia. The current article examines
      how the emotional context, and people's responses to it, are related to emotional
      inertia. We investigated how individual differences in the inertia of negative
      affect (NA) are related to individual differences in exposure, reactivity, and
      recovery from emotional events, in daily life (assessed using experience
      sampling) as well as in the lab (assessed using an emotional film-clip task),
      among 200 participants commencing their first year of tertiary education. This
      dual-method approach allowed us to assess affective responding on different
      timescales, and in response to standardized as well as idiographic emotional
      stimuli. Our most consistent finding, across both methods, was that heightened NA
      inertia is related to decreased NA recovery following negative stimuli,
      suggesting that higher levels of inertia may be mostly driven by impairments in
      affect repair following negative events.

PMID- 25844973
TI  - Emotional clarity as a function of neuroticism and major depressive disorder.
AB  - Investigators have begun to document links between emotional clarity and forms of
      negative emotionality, including neuroticism and major depressive disorder (MDD).
      Researchers to date have relied almost exclusively on global self-reports of
      emotional clarity; moreover, no studies have examined emotional clarity as a
      function of valence, although this may prove to be crucial in understanding the
      relation of emotional clarity to maladjustment. In 2 studies, we used experience
      sampling methodology and multilevel modeling to examine the associations between
      emotional clarity and 2 constructs that have been linked theoretically with
      emotional clarity: neuroticism and depression. In Study 1 we assessed 95 college
      students who completed a self-report measure of neuroticism. In Study 2 we
      examined 53 adults diagnosed with MDD and 53 healthy adults. Reaction times to
      negative and positive emotion ratings during the experience-sampling protocols
      were used as an indirect measure of emotional clarity. Neuroticism was related to
      lower clarity of negative, but not of positive, emotion. Similarly, compared with
      the healthy controls, individuals with MDD had lower clarity of negative, but not
      of positive, emotion. It is important to note, findings from both studies held
      after controlling for baseline RTs and current levels of negative and positive
      emotion. These findings highlight the importance of assessing valence when
      examining emotional clarity and increase our understanding of the nature of the
      emotional disturbances that characterize neuroticism and MDD.

PMID- 25844975
TI  - Jealousy increased by induced relative left frontal cortical activity.
AB  - Asymmetric frontal cortical activity may be one key to the process linking social
      exclusion to jealous feelings. The current research examined the causal role of
      asymmetric frontal brain activity in modulating jealousy in response to social
      exclusion. Transcranial direct-current stimulation (tDCS) over the frontal cortex
      to manipulate asymmetric frontal cortical activity was combined with a modified
      version of the Cyberball paradigm designed to induce jealousy. After receiving 15
      min of tDCS, participants were excluded by a desired partner and reported how
      jealous they felt. Among individuals who were excluded, tDCS to increase relative
      left frontal cortical activity caused greater levels of self-reported jealousy
      compared to tDCS to increase relative right frontal cortical activity or sham
      stimulation. Limitations concerning the specificity of this effect and
      implications for the role of the asymmetric prefrontal cortical activity in
      motivated behaviors are discussed.

PMID- 25844976
TI  - Statistical evaluation and modeling of cheap substrate-based cultivation medium
      of Chlorella vulgaris to enhance microalgae lipid as new potential feedstock for
      biolubricant.
AB  - Chlorella vulgaris (C. vulgaris) microalga was investigated as a new potential
      feedstock for the production of biodegradable lubricant. In order to enhance
      microalgae lipid for biolubricant production, mixotrophic growth of C. vulgaris
      was optimized using statistical analysis of Plackett-Burman (P-B) and response
      surface methodology (RSM). A cheap substrate-based medium of molasses and corn
      steep liquor (CSL) was used instead of expensive mineral salts to reduce the
      total cost of microalgae production. The effects of molasses and CSL
      concentration (cheap substrates) and light intensity on the growth of microalgae
      and their lipid content were analyzed and modeled. Designed models by RSM showed
      good compatibility with a 95% confidence level when compared to the cultivation
      system. According to the models, optimal cultivation conditions were obtained
      with biomass productivity of 0.123 g L(-1) day(-1) and lipid dry weight of 0.64 g
      L(-1) as 35% of dry weight of C. vulgaris. The extracted microalgae lipid
      presented useful fatty acid for biolubricant production with viscosities of 42.00
      cSt at 40 degrees C and 8.500 cSt at 100 degrees C, viscosity index of 185, flash
      point of 185 degrees C, and pour point of -6 degrees C. These properties showed
      that microalgae lipid could be used as potential feedstock for biolubricant
      production. 

PMID- 25844977
TI  - Expert opinion: How and when to perform CT myocardial perfusion imaging.

PMID- 25844978
TI  - Comparison of Digital Tomosynthesis and Chest Radiography for the Detection of
      Noncalcified Pulmonary and Hilar Lesions.
AB  - OBJECTIVES: The aim of this study was to compare the sensitivity and specificity
      of chest digital tomosynthesis (DTS) with chest radiography (CXR) for the
      detection of noncalcified pulmonary nodules and hilar lesions using computed
      tomography (CT) as the reference standard. MATERIALS AND METHODS: A total of 78
      patients with suspected noncalcified pulmonary lesions on CXR were included in
      the study. Two radiologists, blinded to the history and CT, analyzed the CXR and
      the DTS images (separately), whereas a third radiologist analyzed the CXR and DTS
      images together. Noncalcified intrapulmonary nodules and hilar lesions were
      recorded for analysis. The interobserver agreement for CXR and DTS was assessed,
      and the time taken to report the images was recorded. RESULTS: A total of 202
      lesions were recorded in 78 patients. There were 111 true lesions confirmed on CT
      in 53 patients; in 25 patients subsequent CT excluded a lesion. The overall
      sensitivity was 32% for CXR and 49% for DTS. This improved to 54% when the
      posteroanterior CXR and DTS were reviewed together (CXR-DTS). The overall
      specificities for CXR, DTS, and CXR-DTS were 49%, 96%, and 98%, respectively.
      There were 56 suspected hilar lesions with subgroup sensitivities of 76% for CXR,
      65% for DTS, and 76% for CXR-DTS. The specificity for hilar lesions was 59%, 92%,
      and 97% for CXR, DTS, and CXR-DTS, respectively. CONCLUSIONS: DTS significantly
      improves the detectability of noncalcified nodules when compared with and when
      used in combination with CXR. The specificity and interobserver agreement of DTS
      in the diagnosis of suspected noncalcified pulmonary nodules and hilar lesions
      are significantly better than those of CXR and approaches those of CT.

PMID- 25844979
TI  - Signs in cardiopulmonary imaging: luftsichel sign.

PMID- 25844980
TI  - Nutritional and other types of oedema, albumin, complex carbohydrates and the
      interstitium - a response to Malcolm Coulthard's hypothesis: Oedema in
      kwashiorkor is caused by hypo-albuminaemia.
AB  - The various types of oedema in man are considered in relation to Starling's
      hypothesis of fluid movement from capillaries, with the main emphasis on
      nutritional oedema and the nephrotic syndrome in children. It is concluded that
      each condition has sufficient anomalous findings to render Starling's hypothesis
      untenable. The finding that the endothelial glycocalyx is key to control of fluid
      movement from and into the capillaries calls for complete revision of our
      understanding of oedema formation. The factors so far known to affect the
      function of the glycocalyx are reviewed. As these depend upon sulphated
      proteoglycans and other glycosaminoglycans, the argument is advanced that the
      same abnormalities will extend to the interstitial space and that kwashiorkor is
      fundamentally related to a defect in sulphur metabolism which can explain all the
      clinical features of the condition, including the formation of oedema. 

PMID- 25844981
TI  - Refining the closed loop in the data age: research-to-practice transitions in
      diabetes technology.

PMID- 25844982
TI  - Factors that affect job satisfaction and intention to leave of allied health
      professionals in a metropolitan hospital.
AB  - OBJECTIVE: The purpose of the present study was to determine the aspects of the
      allied health professional's job that contribute most to job satisfaction and
      intention to leave in a metropolitan hospital. METHOD: Data were collected via a
      questionnaire that was emailed to all clinical allied health staff at
      Campbelltown and Camden Hospitals in New South Wales, Australia. The participants
      then rated their level of satisfaction with various job.aspects. RESULTS: A
      significant correlation was found between several job satisfaction factors and
      intention to leave in this study group, including quality of supervision, level
      of competency to do the job, recognition for doing the job, advancement
      opportunities, autonomy, feelings of worthwhile accomplishment, communication and
      support from the manager. CONCLUSION: In relation to Herzberg's job satisfaction
      theory, both intrinsic and extrinsic work factors have been shown to have a
      significant correlation with intention to leave in this study group. This
      information can assist workforce planners to implement strategies to improve
      retention levels of allied health professionals in the work place.

PMID- 25844983
TI  - Electronic Alteration on Oligothiophenes by o-Carborane: Electron Acceptor
      Character of o-Carborane in Oligothiophene Frameworks with Dicyano-Vinyl End-On
      Group.
AB  - We studied electronic change in oligothiophenes by employing o-carborane into a
      molecular array in which one or both end(s) were substituted by electron
      withdrawing dicyano-vinyl group(s). Depending on mono- or bis-substitution at the
      o-carborane, a series of linear A1-D-A2 (1a-1c) or V-shaped A1-D-A2-D-A1 (2a-2c)
      oligothiophene chain structures of variable length were prepared; A1, D, and A2,
      represent dicyano-vinyl, oligothiophenyl, and o-carboranyl groups, respectively.
      Among this series, 2a shows strong electron-acceptor capability of o-carborane
      comparable to that of the dicyano-vinyl substituent, which can be elaborated by a
      conformational effect driven by cage sigma*-pi* interaction. As a result,
      electronic communications between o-carborane and dicyano-vinyl groups are
      successfully achieved in 2a. 

PMID- 25844987
TI  - Error in group information and figure.

PMID- 25844984
TI  - Selecting the best candidates for lung cancer screening.

PMID- 25844988
TI  - Sudden painless nail shedding. Hand-foot-and-mouth disease (HFMD).

PMID- 25844989
TI  - JAMA pediatrics patient page. Keeping children and adolescents safe from
      firearms.

PMID- 25844990
TI  - Association between admission temperature and mortality and major morbidity in
      preterm infants born at fewer than 33 weeks' gestation.
AB  - IMPORTANCE: Neonatal hypothermia has been associated with higher mortality and
      morbidity; therefore, thermal control following delivery is an essential part of
      neonatal care. Identifying the ideal body temperature in preterm neonates in the
      first few hours of life may be helpful to reduce the risk for adverse outcomes.
      OBJECTIVES: To examine the association between admission temperature and neonatal
      outcomes and estimate the admission temperature associated with lowest rates of
      adverse outcomes in preterm infants born at fewer than 33 weeks' gestation.
      DESIGN, SETTING, AND PARTICIPANTS: Retrospective observational study at 29
      neonatal intensive care units in the Canadian Neonatal Network. Participants
      included 9833 inborn infants born at fewer than 33 weeks' gestation who were
      admitted between January 1, 2010, and December 31, 2012. EXPOSURE: Axillary or
      rectal body temperature recorded at admission. MAIN OUTCOMES AND MEASURES: The
      primary outcome was a composite adverse outcome defined as mortality or any of
      the following: severe neurological injury, severe retinopathy of prematurity,
      necrotizing enterocolitis, bronchopulmonary dysplasia, or nosocomial infection.
      The relationships between admission temperature and the composite outcome as well
      as between admission temperature and the components of the composite outcome were
      evaluated using multivariable analyses. RESULTS: Admission temperatures of the
      9833 neonates were distributed as follows: lower than 34.5 degrees C (1%); 34.5
      degrees C to 34.9 degrees C (1%); 35.0 degrees C to 35.4 degrees C (3%); 35.5
      degrees C to 35.9 degrees C (7%); 36.0 degrees C to 36.4 degrees C (24%); 36.5
      degrees C to 36.9 degrees C (38%); 37.0 degrees C to 37.4 degrees C (19%); 37.5
      degrees C to 37.9 degrees C (5%); and 38.0 degrees C or higher (2%). After
      adjustment for maternal and infant characteristics, the rates of the composite
      outcome, severe neurological injury, severe retinopathy of prematurity,
      necrotizing enterocolitis, bronchopulmonary dysplasia, and nosocomial infection
      had a U-shaped relationship with admission temperature (alpha > 0 [P < .05]). The
      admission temperature at which the rate of the composite outcome was lowest was
      36.8 degrees C (95% CI, 36.7 degrees C-37.0 degrees C). Rates of severe
      neurological injury, severe retinopathy of prematurity, necrotizing enterocolitis
      (95% CI, 36.3 degrees C-36.7 degrees C), bronchopulmonary dysplasia, and
      nosocomial infection (95% CI, 36.9 degrees C-37.3 degrees C) were lowest at
      admission temperatures ranging from 36.5 degrees C to 37.2 degrees C. CONCLUSIONS
      AND RELEVANCE: The relationship between admission temperature and adverse
      neonatal outcomes was U-shaped. The lowest rates of adverse outcomes were
      associated with admission temperatures between 36.5 degrees C and 37.2 degrees C.

PMID- 25844991
TI  - Risk for incident diabetes mellitus following initiation of second-generation
      antipsychotics among Medicaid-enrolled youths.
AB  - IMPORTANCE: Second-generation antipsychotics (SGAs) have increasingly been
      prescribed to Medicaid-enrolled children, either singly or in a medication
      combination. Although metabolic adverse effects have been linked to SGA use in
      youths, estimating the risk for type 2 diabetes mellitus, a rarer outcome, has
      been challenging. OBJECTIVE: To determine whether SGA initiation was associated
      with an increased risk for incident type 2 diabetes mellitus. Secondary analyses
      examined the risk associated with multiple-drug regimens, including stimulants
      and antidepressants, as well as individual SGAs. DESIGN, SETTING, AND
      PARTICIPANTS: Retrospective national cohort study of Medicaid-enrolled youths
      between January 2003 and December 2007. In this observational study using
      national Medicaid Analytic eXtract data files, initiators and noninitiators of
      SGAs were identified in each month. Included in this study were US youths aged 10
      to 18 years with a mental health diagnosis and enrolled in a Medicaid fee-for
      service arrangement during the study. Those with chronic steroid exposure, a
      diagnosis of diabetes mellitus, or SGA use during a 1-year look-back period were
      ineligible. The mean follow-up time for all participants was 17.2 months. Youths
      were followed up until diagnosis of diabetes mellitus or end of follow-up owing
      to censoring caused by the transition into a Medicaid managed care arrangement or
      Medicaid ineligibility (the end of available data). Propensity weights were
      developed to balance observed demographic and clinical characteristics between
      exposure groups. Discrete failure time models were fitted using weighted logistic
      regression to estimate the risk for incident diabetes mellitus between initiators
      and noninitiators. EXPOSURE: A filled SGA prescription. MAIN OUTCOMES AND
      MEASURES: Incident type 2 diabetes mellitus identified through visit and pharmacy
      claims during the observation period. RESULTS: Among 107,551 SGA initiators and
      1,221,434 noninitiators, the risk for incident diabetes mellitus was increased
      among initiators (odds ratio [OR], 1.51; 95% CI, 1.35-1.69; P < .001). Compared
      with youths initiating only SGAs, the risk was higher among SGA initiators who
      used antidepressants concomitantly at the time of SGA initiation (OR, 1.54; 95%
      CI, 1.17-2.03; P = .002) but was not significantly different for SGA initiators
      who were concomitantly using stimulants. As compared with a reference group of
      risperidone initiators, the risk was higher among those initiating ziprasidone
      (OR, 1.61; 95% CI, 0.99-2.64; P = .06) and aripiprazole (OR, 1.58; 95% CI, 1.21
      2.07; P = .001) but not quetiapine fumarate or olanzapine. CONCLUSIONS AND
      RELEVANCE: The risk for incident type 2 diabetes mellitus was increased among
      youths initiating SGAs and was highest in those concomitantly using
      antidepressants. Compared with risperidone, newer antipsychotics were not
      associated with decreased risk.

PMID- 25844992
TI  - Failure to cancel tests: a case of an unnecessary joint arthrocentesis: a
      teachable moment.

PMID- 25844993
TI  - Neurologic Function and Health-Related Quality of Life in Patients Following
      Targeted Temperature Management at 33 degrees C vs 36 degrees C After Out-of
      Hospital Cardiac Arrest: A Randomized Clinical Trial.
AB  - IMPORTANCE: Brain injury affects neurologic function and quality of life in
      survivors after cardiac arrest. OBJECTIVE: To compare the effects of 2 target
      temperature regimens on long-term cognitive function and quality of life after
      cardiac arrest. DESIGN, SETTING, AND PARTICIPANTS: In this multicenter,
      international, parallel group, assessor-masked randomized clinical trial
      performed from November 11, 2010, through January 10, 2013, we enrolled 950
      unconscious adults with cardiac arrest of presumed cardiac cause from 36
      intensive care units in Europe and Australia. Eleven patients were excluded from
      analysis for a total sample size of 939. INTERVENTIONS: Targeted temperature
      management at 33 degrees C vs 36 degrees C. MAIN OUTCOMES AND MEASURES: Cognitive
      function was measured by the Mini-Mental State Examination (MMSE) and assessed by
      observers through the Informant Questionnaire on Cognitive Decline in the Elderly
      (IQCODE). Patients reported their activities in daily life and mental recovery
      through Two Simple Questions and their quality of life through the Medical
      Outcomes Study 36-Item Short Form Health Survey, version 2. RESULTS: In the
      modified intent-to-treat population, including nonsurvivors, the median MMSE
      score was 14 in the 33 degrees C group (interquartile range [IQR], 0-28) vs 17 in
      the 36 degrees C group (IQR, 0-29) (P = .77), and the IQCODE score was 115 (IQR,
      79-130) vs 115 (IQR, 80-130) (P = .57) in the 33 degrees C and 36 degrees C
      groups, respectively. The median MMSE score for survivors was within the
      reference range and similar (33 degrees C group median, 28; IQR, 26-30; vs 36
      degrees C group median, 28; IQR, 25-30; P = .61). The median IQCODE score was
      within the minor deficit range (33 degrees C group median, 79.5; IQR, 78.0-85.9;
      vs 36 degrees C group median, 80.7; IQR, 78.0-86.9; P = .04). A total of 18.8% vs
      17.5% of survivors reported needing help with everyday activities (P = .71), and
      66.5% in the 33 degrees C group vs 61.8% in the 36 degrees C group reported that
      they thought they had made a complete mental recovery (P = .32). The mean (SD)
      mental component summary score was 49.1 (12.5) vs 49.0 (12.2) (P = .79), and the
      mean (SD) physical component summary score was 46.8 (13.8) and 47.5 (13.8) (P =
      .45), comparable to the population norm. CONCLUSIONS AND RELEVANCE: Quality of
      life was good and similar in patients with cardiac arrest receiving targeted
      temperature management at 33 degrees C or 36 degrees C. Cognitive function was
      similar in both intervention groups, but many patients and observers reported
      impairment not detected previously by standard outcome scales. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT01020916.

PMID- 25844994
TI  - Comorbid Adolescent Difficulties: Social Work Prevention of Delinquency and
      Serious Youthful Offending.
AB  - A majority of adolescents who are formally involved with the juvenile courts and
      detained or incarcerated are dealing with past or present maltreatment
      victimization, learning disabilities, and/or mental health/substance abuse
      difficulties. Addressing these problems and traumas is an integral part of
      preventing delinquency and breaking a youthful offender's recidivist cycle, a
      pattern that often predicts adult offending and incarceration. Fortunately, there
      are effective programs across the social work profession that decrease or may
      even eliminate delinquent behaviors, both for low-level and more serious youthful
      offenders. Unfortunately, the use of these social work preventative programs is
      not consistent or extensive within the juvenile justice system. 

PMID- 25844995
TI  - Surgery versus nonsurgical treatment of lumbar spinal stenosis: a randomized
      trial.
AB  - BACKGROUND: Primary care management decisions for patients with symptomatic
      lumbar spinal stenosis (LSS) are challenging, and nonsurgical guidance is limited
      by lack of evidence. OBJECTIVE: To compare surgical decompression with physical
      therapy (PT) for LSS and evaluate sex differences. DESIGN: Multisite randomized,
      controlled trial. (ClinicalTrials.gov: NCT00022776). SETTING: Neurologic and
      orthopedic surgery departments and PT clinics. PARTICIPANTS: Surgical candidates
      with LSS aged 50 years or older who consented to surgery. INTERVENTION: Surgical
      decompression or PT. MEASUREMENTS: Primary outcome was physical function score on
      the Short Form-36 Health Survey at 2 years assessed by masked testers. RESULTS:
      The study took place from November 2000 to September 2007. A total of 169
      participants were randomly assigned and stratified by surgeon and sex (87 to
      surgery and 82 to PT), with 24-month follow-up completed by 74 and 73
      participants in the surgery and PT groups, respectively. Mean improvement in
      physical function for the surgery and PT groups was 22.4 (95% CI, 16.9 to 27.9)
      and 19.2 (CI, 13.6 to 24.8), respectively. Intention-to-treat analyses revealed
      no difference between groups (24-month difference, 0.9 [CI, -7.9 to 9.6]).
      Sensitivity analyses using causal-effects methods to account for the high
      proportion of crossovers from PT to surgery (57%) showed no significant
      differences in physical function between groups. LIMITATION: Without a control
      group, it is not possible to judge success attributable to either intervention.
      CONCLUSION: Surgical decompression yielded similar effects to a PT regimen among
      patients with LSS who were surgical candidates. Patients and health care
      providers should engage in shared decision-making conversations that include full
      disclosure of evidence involving surgical and nonsurgical treatments for LSS.
      PRIMARY FUNDING SOURCE: National Institutes of Health and National Institute of
      Arthritis and Musculoskeletal and Skin Diseases.

PMID- 25844996
TI  - The optimal imaging strategy for patients with stable chest pain: a cost
      effectiveness analysis.
AB  - BACKGROUND: The optimal imaging strategy for patients with stable chest pain is
      uncertain. OBJECTIVE: To determine the cost-effectiveness of different imaging
      strategies for patients with stable chest pain. DESIGN: Microsimulation state
      transition model. DATA SOURCES: Published literature. TARGET POPULATION: 60-year
      old patients with a low to intermediate probability of coronary artery disease
      (CAD). TIME HORIZON: Lifetime. PERSPECTIVE: The United States, the United
      Kingdom, and the Netherlands. INTERVENTION: Coronary computed tomography (CT)
      angiography, cardiac stress magnetic resonance imaging, stress single-photon
      emission CT, and stress echocardiography. OUTCOME MEASURES: Lifetime costs,
      quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios.
      RESULTS OF BASE-CASE ANALYSIS: The strategy that maximized QALYs and was cost
      effective in the United States and the Netherlands began with coronary CT
      angiography, continued with cardiac stress imaging if angiography found at least
      50% stenosis in at least 1 coronary artery, and ended with catheter-based
      coronary angiography if stress imaging induced ischemia of any severity. For U.K.
      men, the preferred strategy was optimal medical therapy without catheter-based
      coronary angiography if coronary CT angiography found only moderate CAD or stress
      imaging induced only mild ischemia. In these strategies, stress echocardiography
      was consistently more effective and less expensive than other stress imaging
      tests. For U.K. women, the optimal strategy was stress echocardiography followed
      by catheter-based coronary angiography if echocardiography induced mild or
      moderate ischemia. RESULTS OF SENSITIVITY ANALYSIS: Results were sensitive to
      changes in the probability of CAD and assumptions about false-positive results.
      LIMITATIONS: All cardiac stress imaging tests were assumed to be available.
      Exercise electrocardiography was included only in a sensitivity analysis.
      Differences in QALYs among strategies were small. CONCLUSION: Coronary CT
      angiography is a cost-effective triage test for 60-year-old patients who have
      nonacute chest pain and a low to intermediate probability of CAD. PRIMARY FUNDING
      SOURCE: Erasmus University Medical Center.

PMID- 25844998
TI  - Celebrating the ACP Centennial: From the Annals archive-firearm-related harms.

PMID- 25844999
TI  - Surgery for lumbar spinal stenosis: informed patient preferences should weigh
      heavily.

PMID- 25844997
TI  - Efficacy of commercial weight-loss programs: an updated systematic review.
AB  - BACKGROUND: Commercial and proprietary weight-loss programs are popular obesity
      treatment options, but their efficacy is unclear. PURPOSE: To compare weight
      loss, adherence, and harms of commercial or proprietary weight-loss programs
      versus control/education (no intervention, printed materials only, health
      education curriculum, or <3 sessions with a provider) or behavioral counseling
      among overweight and obese adults. DATA SOURCES: MEDLINE and the Cochrane
      Database of Systematic Reviews from inception to November 2014; references
      identified by program staff. STUDY SELECTION: Randomized, controlled trials
      (RCTs) of at least 12 weeks' duration; prospective case series of at least 12
      months' duration (harms only). DATA EXTRACTION: Two reviewers extracted
      information on study design, population characteristics, interventions, and mean
      percentage of weight change and assessed risk of bias. DATA SYNTHESIS: We
      included 45 studies, 39 of which were RCTs. At 12 months, Weight Watchers
      participants achieved at least 2.6% greater weight loss than those assigned to
      control/education. Jenny Craig resulted in at least 4.9% greater weight loss at
      12 months than control/education and counseling. Nutrisystem resulted in at least
      3.8% greater weight loss at 3 months than control/education and counseling. Very
      low-calorie programs (Health Management Resources, Medifast, and OPTIFAST)
      resulted in at least 4.0% greater short-term weight loss than counseling, but
      some attenuation of effect occurred beyond 6 months when reported. Atkins
      resulted in 0.1% to 2.9% greater weight loss at 12 months than counseling.
      Results for SlimFast were mixed. We found limited evidence to evaluate adherence
      or harms for all programs and weight outcomes for other commercial programs.
      LIMITATION: Many trials were short (<12 months), had high attrition, and lacked
      blinding. CONCLUSION: Clinicians could consider referring overweight or obese
      patients to Weight Watchers or Jenny Craig. Other popular programs, such as
      Nutrisystem, show promising weight-loss results; however, additional studies
      evaluating long-term outcomes are needed. PRIMARY FUNDING SOURCE: None. (
      PROSPERO: CRD4201-4007155).

PMID- 25845000
TI  - The role of commercial weight-loss programs.

PMID- 25845001
TI  - Homesick: from Beirut to Rochester.

PMID- 25845003
TI  - Genetic and environmental risk assessment and colorectal cancer screening.

PMID- 25845004
TI  - Genetic and environmental risk assessment and colorectal cancer screening.

PMID- 25845005
TI  - 3D-CAM.

PMID- 25845006
TI  - 3D-CAM.

PMID- 25845007
TI  - Prevention of recurrent nephrolithiasis in adults.

PMID- 25845008
TI  - Prevention of recurrent nephrolithiasis in adults.

PMID- 25845009
TI  - Prevention of recurrent nephrolithiasis in adults.

PMID- 25845010
TI  - Models in the development of clinical practice guidelines.

PMID- 25845011
TI  - Models in the development of clinical practice guidelines.

PMID- 25845012
TI  - Chikungunya.

PMID- 25845013
TI  - Chikungunya.

PMID- 25845014
TI  - Chikungunya.

PMID- 25845015
TI  - Correction: Inviting patients to read their doctors' notes.

PMID- 25845016
TI  - Summaries for patients. Surgery versus physical therapy for treating lumbar
      spinal stenosis.

PMID- 25845018
TI  - Web Exclusives. Annals graphic medicine: Betty P.

PMID- 25845017
TI  - In the clinic. Constipation.
AB  - This issue provides a clinical overview of constipation, focusing on prevention,
      diagnosis, treatment, and patient information. The content of In the Clinic is
      drawn from the clinical information and education resources of the American
      College of Physicians (ACP), including ACP Smart Medicine and MKSAP (Medical
      Knowledge and Self-Assessment Program). Annals of Internal Medicine editors
      develop In the Clinic from these primary sources in collaboration with the ACP's
      Medical Education and Publishing divisions and with the assistance of science
      writers and physician writers. Editorial consultants from ACP Smart Medicine and
      MKSAP provide expert review of the content. Readers who are interested in these
      primary resources for more detail can consult http://smartmedicine.acponline.org,
      http://mksap.acponline.org, and other resources referenced in each issue of In
      the Clinic. 

PMID- 25845019
TI  - Necrotrophic effector epistasis in the Pyrenophora tritici-repentis-wheat
      interaction.
AB  - Pyrenophora tritici-repentis, the causal agent of tan spot disease of wheat,
      mediates disease by the production of host-selective toxins (HST). The known
      toxins are recognized in an 'inverse' gene-for-gene manner, where each is
      perceived by the product of a unique locus in the host and recognition leads to
      disease susceptibility. Given the importance of HSTs in disease development, we
      would predict that the loss of any of these major pathogenicity factors would
      result in reduced virulence and disease development. However, after either
      deletion of the gene encoding the HST ToxA or, reciprocally, heterologous
      expression of ToxA in a race that does not normally produce the toxin followed by
      inoculation of ToxA-sensitive and insensitive wheat cultivars, we demonstrate
      that ToxA symptom development can be epistatic to other HST-induced symptoms.
      ToxA epistasis on certain ToxA-sensitive wheat cultivars leads to genotype
      specific increases in total leaf area affected by disease. These data indicate a
      complex interplay between host responses to HSTs in some genotypes and underscore
      the challenge of identifying additional HSTs whose activity may be masked by
      other toxins. Also, through mycelial staining, we acquire preliminary evidence
      that ToxA may provide additional benefits to fungal growth in planta in the
      absence of its cognate recognition partner in the host. 

PMID- 25845020
TI  - Influence of institutional culture and policies on do-not-resuscitate decision
      making at the end of life.
AB  - IMPORTANCE: Controversy exists regarding whether the decision to pursue a do-not
      resuscitate (DNR) order should be grounded in an ethic of patient autonomy or in
      the obligation to act in the patient's best interest (beneficence). OBJECTIVE: To
      explore how physicians' approaches to DNR decision making at the end of life are
      shaped by institutional cultures and policies surrounding patient autonomy.
      DESIGN, SETTING, AND PARTICIPANTS: We performed semistructured in-depth
      qualitative interviews of 58 internal medicine physicians from 4 academic medical
      centers (3 in the United States and 1 in the United Kingdom) by years of
      experience and medical subspecialty from March 7, 2013, through January 8, 2014.
      Hospitals were selected based on expected differences in hospital culture and
      variations in hospital policies regarding prioritization of autonomy vs best
      interest. MAIN OUTCOMES AND MEASURES: This study identified the key influences of
      institutional culture and policies on physicians' attitudes toward patient
      autonomy in DNR decision making at the end of life. RESULTS: A hospital's
      prioritization of autonomy vs best interest as reflected in institutional culture
      and policy appeared to influence the way that physician trainees conceptualized
      patient autonomy. This finding may have influenced the degree of choice and
      recommendations physician trainees were willing to offer regarding DNR decision
      making. Trainees at hospitals where policies and culture prioritized autonomy
      focused approaches appeared to have an unreflective deference to autonomy and
      felt compelled to offer the choice of resuscitation neutrally in all situations
      regardless of whether they believed resuscitation to be clinically appropriate.
      In contrast, trainees at hospitals where policies and culture prioritized best
      interest-focused approaches appeared to be more comfortable recommending against
      resuscitation in situations where survival was unlikely. Experienced physicians
      at all sites similarly did not exclusively allow their actions to be defined by
      policies and institutional culture and were willing to make recommendations
      against resuscitation if they believed it would be futile. CONCLUSIONS AND
      RELEVANCE: Institutional cultures and policies might influence how physician
      trainees develop their professional attitudes toward autonomy and their
      willingness to make recommendations regarding the decision to implement a DNR
      order. A singular focus on autonomy might inadvertently undermine patient care by
      depriving patients and surrogates of the professional guidance needed to make
      critical end of life decisions.

PMID- 25845021
TI  - Recovery and recurrence following a first episode of mania: a systematic review
      and meta-analysis of prospectively characterized cohorts.
AB  - OBJECTIVE: Information about recurrence rates is useful in informing clinical
      practice, but most data with regard to recurrence rates in bipolar patients come
      from cohorts at different stages of illness. These data are of limited utility in
      estimating risk of relapse in first-episode bipolar disorder. Therefore, the
      objective of this investigation was to synthesize available recurrence data after
      a first episode of mania. DATA SOURCES: We searched MEDLINE, EMBASE, PsycINFO,
      and Cochrane Central Register of Controlled Trials (CENTRAL) from 1980 to January
      24th, 2014, for articles in English, French, or Spanish using (1) bipolar
      disorder (MeSH term) OR manic/mania, AND (2) first* (episode*, hospitalization*
      OR admission*) OR time factor (MeSH term), AND (3) recovery, remission,
      recurrence OR relapse. STUDY SELECTION: 712 articles were screened. Prospective
      cohorts of first-episode mania were included. DATA EXTRACTION: Syndromal
      recovery, symptomatic recovery, and recurrence rates were extracted by 2
      independent raters at 6 months, 1 year, 2 years, and 4 years and analyzed using
      random effects models and meta-regression. RESULTS: We identified 8 studies
      representing a total of 734 first-episode patients. The syndromal recovery rates
      were 77.4% at 6 months and 84.2% at 1 year. Only 62.1% of patients had achieved a
      period of symptomatic recovery within 1 year. Recurrence rates were 25.7% within
      6 months, 41.0% by 1 year, and 59.7% by 4 years. Younger age at first episode was
      associated with risk of recurrence after 1 year. CONCLUSIONS: The majority of
      patients with first-episode mania exhibit syndromal recovery and, to a lesser
      extent, symptomatic recovery. The risk of recurrence is high, although the rates
      are slightly lower than those in mixed cohorts, with greater risk of recurrence
      associated with younger age at onset. Given lower recurrence than among mixed
      cohorts, there may be a window of opportunity to provide optimal treatment early
      and alter disease progression.

PMID- 25845022
TI  - VEGF and dual-EGFR inhibition in colorectal cancer.

PMID- 25845023
TI  - Orthogonal thiol functionalization at a single atomic center for profiling
      transthiolation activity of E1 activating enzymes.
AB  - Transthiolation is a fundamental biological reaction and is utilized by many
      enzymes involved in the conjugation of ubiquitin and ubiquitin-like proteins.
      However, tools that enable selective profiling of this activity are lacking.
      Transthiolation requires cysteine-cysteine juxtaposition; therefore a method that
      enables irreversible "stapling" of proximal thiols would facilitate the
      development of novel probes that could be used to profile this activity. Herein,
      we characterize biocompatible chemistry that enables sequential functionalization
      of cysteines within proteins at a single atomic center. We use our method to
      develop a new class of activity-based probe that profiles transthiolation
      activity of human E1 activating enzymes. We demonstrate use in vitro and in situ
      and compatibility with competitive activity-based protein profiling. We also use
      the probe to gain insight into the determinants of transthiolation between E2 and
      a RING-in-between-RING (RBR) E3 ligase. Furthermore, we anticipate that this
      method of thiol functionalization will have broad utility by enabling simple
      redox-stable cross-linking of proximal cysteines in general. 

PMID- 25845024
TI  - Bio-inspired direct patterning functional nanothin microlines: controllable
      liquid transfer.
AB  - Developing a general and low-cost strategy that enables direct patterning of
      microlines with nanometer thickness from versatile liquid-phase functional
      materials and precise positioning of them on various substrates remains a
      challenge. Herein, with inspiration from the oriental wisdom to control ink
      transfer by Chinese brushes, we developed a facile and general writing strategy
      to directly pattern various functional microlines with homogeneous distribution
      and nanometer-scale thickness. It is demonstrated that the width and thickness of
      the microlines could be well-controlled by tuning the writing method, providing
      guidance for the adaptation of this technique to various systems. It is also
      shown that various functional liquid-phase materials, such as quantum dots, small
      molecules, polymers, and suspensions of nanoparticles, could directly write on
      the substrates with intrinsic physicochemical properties well-preserved.
      Moreover, this technique enabled direct patterning of liquid-phase materials on
      certain microdomains, even in multiple layered style, thus a microdomain
      localized chemical reaction and the patterned surface chemical modification were
      enabled. This bio-inspired direct writing device will shed light on the template
      free printing of various functional micropatterns, as well as the integrated
      functional microdevices. 

PMID- 25845025
TI  - Modeling Pulmonary Disease Pathways Using Recombinant Adeno-Associated Virus 6.2.
AB  - Viral vectors have been applied successfully to generate disease-related animal
      models and to functionally characterize target genes in vivo. However, broader
      application is still limited by complex vector production, biosafety
      requirements, and vector-mediated immunogenic responses, possibly interfering
      with disease-relevant pathways. Here, we describe adeno-associated virus (AAV)
      variant 6.2 as an ideal vector for lung delivery in mice, overcoming most of the
      aforementioned limitations. In a proof-of-concept study using AAV6.2 vectors
      expressing IL-13 and transforming growth factor-beta1 (TGF-beta1), we were able
      to induce hallmarks of severe asthma and pulmonary fibrosis, respectively.
      Phenotypic characterization and deep sequencing analysis of the AAV-IL-13 asthma
      model revealed a characteristic disease signature. Furthermore, suitability of
      the model for compound testing was also demonstrated by pharmacological
      intervention studies using an anti-IL-13 antibody and dexamethasone. Similarly,
      the AAV-TGF-beta1 fibrosis model showed several disease-like pathophenotypes
      monitored by micro-computed tomography imaging and lung function measurement.
      Most importantly, analyses using stuffer control vectors demonstrated that in
      contrast to a common adenovirus-5 vector, AAV6.2 vectors did not induce any
      measurable inflammation and therefore carry a lower risk of altering relevant
      readouts. In conclusion, we propose AAV6.2 as an ideal vector system for the
      functional characterization of target genes in the context of pulmonary diseases
      in mice. 

PMID- 25845026
TI  - Application of Pediatric and Adult Guidelines for Treatment of Lipid Levels Among
      US Adolescents Transitioning to Young Adulthood.
AB  - IMPORTANCE: Health care practitioners who care for adolescents transitioning to
      adulthood often face incongruent recommendations from pediatric and adult
      guidelines for treatment of lipid levels. OBJECTIVE: To compare the proportion of
      young people aged 17 to 21 years who meet criteria for pharmacologic treatment of
      elevated low-density lipoprotein cholesterol (LDL-C) levels under pediatric vs
      adult guidelines. DESIGN, SETTING, AND PARTICIPANTS: We performed a cross
      sectional analysis of the National Health and Nutrition Examination Survey
      (NHANES) population. Surveys were administered from January 1, 1999, through
      December 31, 2012, and the analysis was performed from June through December
      2014. Participants included 6338 individuals aged 17 to 21 years in the United
      States. MAIN OUTCOMES AND MEASURES: To estimate the number and proportion of
      individuals aged 17 to 21 years in the NHANES population who were eligible for
      statin therapy, we applied treatment algorithms from the 2011 Integrated
      Guidelines for Cardiovascular Health and Risk Reduction in Children and
      Adolescents of the National Heart, Lung, and Blood Institute and the 2013
      Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic
      Cardiovascular Risk in Adults from the American College of Cardiology and
      American Heart Association. After imputing missing data and applying NHANES
      sampling weights, we extrapolated the results to 20.4 million
      noninstitutionalized young people aged 17 to 21 years living in the United
      States. RESULTS: Of the 6338 young people aged 17 to 21 years in the NHANES
      population, 2.5% (95% CI, 1.8%-3.2%) would qualify for statin treatment under the
      pediatric guidelines compared with 0.4% (95% CI, 0.1%-0.8%) under the adult
      guidelines. Participants who met pediatric criteria had lower mean (SD) LDL-C
      levels (167.3 [3.8] vs 210.0 [7.1] mg/dL) but higher proportions of other
      cardiovascular risk factors, including hypertension (10.8% vs 8.4%), smoking
      (55.0% vs 23.9%), and obesity (67.7% vs 18.2%) compared with those who met the
      adult guidelines. Extrapolating to the US population of individuals aged 17 to 21
      years represented by the NHANES sample, 483 500 (95% CI, 482 100-484 800) young
      people would be eligible for treatment of LDL-C levels if the pediatric
      guidelines were applied compared with only 78 200 (95% CI, 77 600-78 700) if the
      adult guidelines were applied. CONCLUSIONS AND RELEVANCE: Application of
      pediatric vs adult guidelines for lipid levels, which consider additional
      cardiovascular risk factors beyond age and LDL-C concentration, might result in
      statin treatment for more than 400 000 additional adolescents and young adults.

PMID- 25845027
TI  - Highly Active Gold(I)-Silver(I) Oxo Cluster Activating sp3 C-H Bonds of Methyl
      Ketones under Mild Conditions.
AB  - The activation of C(sp(3))-H bonds is challenging, due to their high bond
      dissociation energy, low proton acidity, and highly nonpolar character. Herein we
      report a unique gold(I)-silver(I) oxo cluster protected by hemilabile phosphine
      ligands [OAu3Ag3(PPhpy2)3](BF4)4 (1), which can activate C(sp(3))-H bonds under
      mild conditions for a broad scope of methyl ketones (RCOCH3, R = methyl, phenyl,
      2-methylphenyl, 2-aminophenyl, 2-hydroxylphenyl, 2-pyridyl, 2-thiazolyl, tert
      butyl, ethyl, isopropyl). Activation happens via triple deprotonation of the
      methyl group, leading to formation of heterometallic Au(I)-Ag(I) clusters with
      formula RCOCAu4Ag4(PPhpy2)4(BF4)5 (PPhpy2 = bis(2-pyridyl)phenylphosphine).
      Cluster 1 can be generated in situ via the reaction of [OAu3Ag(PPhpy2)3](BF4)2
      with 2 equiv of AgBF4. The oxo ion and the metal centers are found to be
      essential in the cleavage of sp(3) C-H bonds of methyl ketones. Interestingly,
      cluster 1 selectively activates the C-H bonds in -CH3 rather than the N-H bonds
      in -NH2 or the O-H bond in -OH which is traditionally thought to be more reactive
      than C-H bonds. Control experiments with butanone, 3-methylbutanone, and
      cyclopentanone as substrates show that the auration of the C-H bond of the
      terminal methyl group is preferred over secondary or tertiary sp(3) C-H bonds; in
      other words, the C-H bond activation is influenced by steric effect. This work
      highlights the powerful reactivity of metal clusters toward C-H activation and
      sheds new light on gold(I)-mediated catalysis. 

PMID- 25845028
TI  - Spatially Mapping Energy Transfer from Single Plasmonic Particles to
      Semiconductor Substrates via STEM/EELS.
AB  - Energy transfer from plasmonic nanoparticles to semiconductors can expand the
      available spectrum of solar energy-harvesting devices. Here, we spatially and
      spectrally resolve the interaction between single Ag nanocubes with insulating
      and semiconducting substrates using electron energy-loss spectroscopy,
      electrodynamics simulations, and extended plasmon hybridization theory. Our
      results illustrate a new way to characterize plasmon-semiconductor energy
      transfer at the nanoscale and bear impact upon the design of next-generation
      solar energy-harvesting devices. 

PMID- 25845029
TI  - The Flocculating Cationic Polypetide from Moringa oleifera Seeds Damages
      Bacterial Cell Membranes by Causing Membrane Fusion.
AB  - A cationic protein isolated from the seeds of the Moringa oleifera tree has been
      extensively studied for use in water treatment in developing countries and has
      been proposed for use in antimicrobial and therapeutic applications. However, the
      molecular basis for the antimicrobial action of this peptide, Moringa oleifera
      cationic protein (MOCP), has not been previously elucidated. We demonstrate here
      that a dominant mechanism of MOCP antimicrobial activity is membrane fusion. We
      used a combination of cryogenic electron microscopy (cryo-EM) and fluorescence
      assays to observe and study the kinetics of fusion of membranes in liposomes
      representing model microbial cells. We also conducted cryo-EM experiments on E.
      coli cells where MOCP was seen to fuse the inner and outer membranes. Coarse
      grained molecular dynamics simulations of membrane vesicles with MOCP molecules
      were used to elucidate steps in peptide adsorption, stalk formation, and fusion
      between membranes. 

PMID- 25845030
TI  - Solvent accessible surface area-based hot-spot detection methods for protein
      protein and protein-nucleic acid interfaces.
AB  - Due to the importance of hot-spots (HS) detection and the efficiency of
      computational methodologies, several HS detecting approaches have been developed.
      The current paper presents new models to predict HS for protein-protein and
      protein-nucleic acid interactions with better statistics compared with the ones
      currently reported in literature. These models are based on solvent accessible
      surface area (SASA) and genetic conservation features subjected to simple Bayes
      networks (protein-protein systems) and a more complex multi-objective genetic
      algorithm-support vector machine algorithms (protein-nucleic acid systems). The
      best models for these interactions have been implemented in two free Web tools. 

PMID- 25845031
TI  - Cancer information seekers in china: a preliminary profile.
AB  - Cancer is now the leading cause of death in China. Effective communication about
      cancer risk and prevention is an important component of cancer control. Yet,
      research in this area is very limited in China. This study used probability
      sample survey data from 2 Chinese cities (Beijing and Hefei, Anhui Province) to
      investigate potential predictors of self-initiated cancer information seeking.
      Analysis showed that cancer information seekers in China were likely to be
      married, relatively educated, earning modest incomes, living in rural areas,
      smoking occasionally, having a family cancer history, relatively trusting of the
      media for health information, somewhat knowledgeable about cancer, having
      nonfatalistic attitudes about cancer, and seeing a personal need for more cancer
      information. The pattern of results, particularly the lack of influence of
      personal health and risk perception factors, highlights the possibility that
      seeking for others might be more prevalent than seeking for self in China.
      Overall, findings suggest that emphasizing family need and mobilizing family
      support might be a productive approach to cancer communication interventions in
      China. 

PMID- 25845033
TI  - The use of novel oral anticoagulants: the debate continues!

PMID- 25845034
TI  - The treatment of venous thromboembolism with novel oral anticoagulants: warnings
      and limitations.

PMID- 25845035
TI  - Which patients with venous thromboembolism should receive non-vitamin K
      antagonist oral anticoagulants? The majority.

PMID- 25845036
TI  - Antipsychotic prescriptions in Iraq and Afghanistan veterans with posttraumatic
      stress disorder in Department of Veterans Affairs healthcare, 2007-2012.
AB  - OBJECTIVE: Antipsychotic medications have been increasingly prescribed for off
      label uses, including treatment of posttraumatic stress disorder (PTSD). Given
      limited knowledge about their use in returning Iraq and Afghanistan veterans with
      PTSD, we explored rates of antipsychotic use in this population and correlations
      with sociodemographic, military service, and psychiatric factors. METHOD: Iraq
      and Afghanistan veterans with a PTSD diagnosis based on ICD-9-CM codes enrolled
      in Veterans Administration care between January 1, 2007, and September 30, 2011,
      were followed through September 30, 2012. Patients with a comorbid diagnosis of
      schizophrenia or bipolar disorder were excluded. Poisson regression models
      evaluated factors associated with prescriptions for antipsychotic versus other
      psychiatric medications (primary outcome). RESULTS: The mean age of our study
      population was 29.3 years, and 9.4% were women. Of 186,460 veterans with PTSD
      diagnoses examined, 19.9% received no psychiatric medications, and the remainder
      received psychiatric medications that excluded (61.2%) or included (18.9%)
      antipsychotics. In adjusted models, several factors were independently associated
      with antipsychotic use, including male sex (adjusted relative risk = 1.25; 95%
      CI, 1.20-1.30) and enlisted rank (1.44; 95% CI, 1.35-1.53). Increased likelihood
      of antipsychotic prescribing was associated with suicidal ideation (4.77; 95% CI,
      4.59-4.95) and comorbid psychiatric diagnoses including personality disorder
      (4.27; 95% CI, 4.09-4.46), drug use disorder (3.56; 95% CI, 3.43-3.69), and
      alcohol use disorder (2.75; 95% CI, 2.65-2.84). CONCLUSIONS: A substantial
      minority of Iraq and Afghanistan veterans diagnosed with PTSD received
      antipsychotics. Male veterans, those of enlisted rank, and those with suicidal
      ideation and psychiatric comorbidities were more likely to receive antipsychotics
      than other types of psychiatric medications. Providers should be cautious about
      antipsychotic use, given their known metabolic risks and questionable benefits
      for PTSD.

PMID- 25845037
TI  - [In memory of Vasily Khristoforovich Anestiadi].

PMID- 25845038
TI  - Author's reply: To PMID 25254521.

PMID- 25845039
TI  - Author's reply: To PMID 25003687.

PMID- 25845040
TI  - Author's reply.

PMID- 25845041
TI  - Author's reply.

PMID- 25845042
TI  - Author's reply: To PMID 24818624.

PMID- 25845043
TI  - Author's reply.

PMID- 25845045
TI  - Author's reply.

PMID- 25845044
TI  - Author's reply.

PMID- 25845046
TI  - PDX-1 (pancreatic/duodenal homeobox-1 protein 1).
AB  - The homeodomain-containing transcription factor pancreatic duodenal homeobox 1
      (PDX-1) plays a key role in pancreatic development and beta-cell function. It is
      a major regulator of transcription in pancreatic cells, and transactivates the
      insulin gene by binding to a specific DNA motif in its promoter region. Glucose
      also regulates insulin gene transcription through PDX-1. It has been shown that
      PDX-1 is required for maintaining pancreatic islet functions by activating gene
      expression and has a dual role in pancreatic development. It initially
      contributes to pancreatic formation during embryogenesis and subsequently
      regulates the pancreatic islet cell physiology in mature islet cells. Because of
      this key role in the embryologic development of the pancreas, PDX-1 expression
      has been investigated in pancreatic cancer cell lines and human tumors. Moreover,
      a few reports have described expression of PDX-1 in other human neoplasms and
      have investigated its potential role in differential diagnosis, but data on
      normal human tissues are lacking. Understanding the molecular mechanisms of
      pancreas formation, and especially the function of PDX-1, may contribute to the
      improved treatment and prevention of debilitating diseases such as diabetes,
      insulinomas and pancreatic carcinomas. Nevertheless, further studies are needed
      concerning its possible application in routine practice.

PMID- 25845047
TI  - Lipomatous angiomyofibroblastoma of the vulva: diagnostic and histogenetic
      considerations.
AB  - We report a rare case of angiomyofibroblastoma (AMFB) of the vulva, composed
      predominantly of a mature fatty component, representing approximately 60% of the
      entire tumour. The tumour, designated as "lipomatous AMFB", should be interpreted
      as the morphological result of an unbalanced bidirectional differentiation of the
      presumptive precursor stromal cell resident in the hormonally-responsive stroma
      of the lower genital tract, with the adipocytic component overwhelming the
      fibroblastic/myofibroblastic one. The close admixture of adipocytes with
      spindled/epithelioid cells of the conventional AMFB resulted, focally, in a
      pseudo-infiltrative growth pattern and pseudo-lipoblast-like appearance, raising
      problems in differential diagnosis, especially with well-differentiated lipoma
      like liposarcoma and spindle cell liposarcoma. Awareness of the possibility that
      vulvo-vaginal AMFB may contain large amount of lipomatous component is crucial to
      avoid confusion with other bland-looking spindle cell tumours containing
      infiltrating fat.

PMID- 25845048
TI  - A peculiar fibroma-like lesion of superficial soft tissue: morphologic and
      immunophenotypic evaluation.
AB  - Apeculiar lesion of superficial soft tissue characterised by fibroma-like
      morphology and an immunohistochemical profile consisting of CK+, VIM+, CD34+,
      CD31+/-, FLI1+ and INI-1 retained is described. The lesion entered into
      differential diagnosis with the so-called fibroma-like variant of epithelioid
      sarcoma, with the entities defined as ES-like/pseudomyogenic
      haemangioendothelioma and the recently identified entity defined as superficial
      CD34+ fibroblastic tumour. All of these entities share a common morphological
      structure, but differ in their immunophenotypic profile.

PMID- 25845049
TI  - Mixed stromal and smooth muscle tumours of the uterus: a report of two cases.
AB  - Mixed stromal and smooth muscle uterine tumours, defined as those containing at
      least 30% of each component as seen by routine light microscopy, are rare. This
      report describes the morphological features of two such tumours diagnosed in 44
      year-old and 50-year-old females complaining from recurrent uterine bleeding that
      was unresponsive to medical treatment. Morphological and immunohistochemical
      evaluations were performed, and a final diagnosis of mixed endometrial stromal
      nodule and smooth muscle tumour of the uterus was rendered in both cases.

PMID- 25845050
TI  - Primary mediastinal angiosarcoma: a rare observation in a patient with 8-year
      survival.
AB  - BACKGROUND: Vascular tumours of the mediastinum are rare, accounting for 1-2% of
      all mediastinal tumours in this location. Angiosarcomas are most often
      encountered as sporadic lesions, typically in the scalp or face of elderly
      patients. However, they can occur in any anatomic site. Mediastinal angiosarcomas
      (MA) are very rare with less than 50 cases reported. CASE REPORT: The authors
      describe the case of a 38-year-old woman whose past medical history was
      consistent for a MA that was diagnosed in 2003. This tumour was treated by
      complete surgical resection followed by radiation therapy and chemotherapy.
      Diagnosis was based on histologic examination. In 2011, the patient presented a
      pleural localisation of the angiosarcoma and died one month after admission, 8
      years after diagnosis of the MA. CONCLUSION: MA is a very rare tumour causing a
      diagnostic dilemma. Clinical and radiologic findings are non-specific, and final
      diagnosis is based on histologic examination. The case described is unusual
      considering the long period of survival, which may be explained by the treatment
      modalities associating complete surgical resection, chemotherapy and radiation
      therapy.

PMID- 25845051
TI  - Dermatofibrosarcoma protuberans of the vulva: a mesenchymal tumour with a broad
      differential diagnosis and review of literature.
AB  - Dermatofibrosarcoma protuberans (DFSP) is a malignant cutaneous soft tissue
      tumour, which rarely presents in the vulva. We report an unusual case of this
      tumour involving the vulva. A 61-year-old female presented with a mass in the
      left mons pubis. Subsequent excisional biopsy of the mass was performed.
      Histologic evaluation of the specimen showed a spindle cell lesion consisting of
      fibroblast-like cells arranged in a storiform pattern. On average, there were 2
      to 3 mitotic figures per 10 high power field (hpf). The neoplastic cells showed
      extension into the surrounding fibroadipose tissue. A panel of
      immunohistochemical stains including CD34, S-100, melan-A, HMB-45, vimentin and
      smooth muscle actin (SMA) were tested. The neoplastic cells showed diffuse
      staining with CD34 and vimentin, while the rest were negative. Based on the
      morphologic and immunohistochemical staining pattern, a diagnosis of DFSP was
      rendered. The patient underwent two subsequent resections before she had clear
      resection margins. The postoperative course was unremarkable. The patient is
      disease free without recurrence after a follow-up of 12 months. DFSP infrequently
      involves the vulva and should be considered in the differential diagnosis of
      other spindle cell lesions presenting in this unusual site. The role of
      immunohistochemical staining with CD34 is imperative in establishing the
      diagnosis. The rate of local reoccurrence is high, but it rarely shows
      metastasis. Treatment of choice is wide local surgical excision with close follow
      up to detect reoccur- rence.

PMID- 25845052
TI  - Unusual presentation of metastatic adenoid cystic carcinoma: a challenge in
      aspiration cytology of the thyroid.
AB  - INTRODUCTION: Adenoid cystic carcinoma is a malignant neoplasm most commonly
      originating in the salivary glands. Its occurrence elsewhere is rare and its
      metastasis to the thyroid gland has been described only once. CASE REPORT: We
      describe the case of a 66-year-old man who presented for a swelling in the
      midline neck of six months duration. A solitary palpable nodule was identified in
      the isthmic region of the thyroid. Fine needle aspiration of the nodule revealed
      high cellularity, a partial microfollicle-like pattern and the presence of small
      hyaline globules. The neoplastic population was composed of monomorphic cells
      with basaloid appearance. Thyroid primitivity was excluded on the basis of the
      negativity for TTF1 and thyroglobulin. As the patient referred an ulcerative
      lesion of the inferior lip, fine needle aspiration cytology of the lesion was
      performed, yielding a diagnosis of adenoid cystic carcinoma. CONCLUSION: The
      present case highlights the need to be aware of possible metastatic thyroid
      localisation of adenoid cystic carcinoma also originating in minor salivary
      glands of the oral cavity. This is a very rare event, but it should be taken into
      consideration and clinical and cytological findings must be carefully examined.

PMID- 25845054
TI  - [The responsibility of the physician before the Judiciary Accountant after an
      innovative address coordination given by the Prosecutor of Lazio].

PMID- 25845053
TI  - Gastrointestinal stromal tumour of the stomach with osseous differentiation: a
      case report.
AB  - Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal neoplasm
      of the gastrointestinal tract, while osseous metaplasia of this tumour is an
      unexpected event. To date, no cases have been reported in the literature. Herein,
      we report a case of a 60-year-old man affected by a GIST with benign osseous
      metaplasia and mature bone formation. We also discuss the pathogenesis of
      intratumoural ossification and review the relevant literature. The prognostic
      significance of ossification in GIST remains unclear because of the limited cases
      reported.

PMID- 25845055
TI  - [Prospective general risk in Anatomical Pathology].

PMID- 25845056
TI  - Preliminary findings from the Oranga Niho dental student outplacement project.
AB  - OBJECTIVES: To examine stakeholder perspectives of the Bachelor of Dental Surgery
      2012-2013 clinical outplacement programme with Maori Oral Health Providers
      (MOHPs) and inform the programme's ongoing development. DESIGN: A mixed methods
      kaupapa Maori action research project. SETTING: Six North Island MOHPs and the
      University of Otago Faculty of Dentistry. PARTICIPANTS AND METHODS: Online
      questionnaires were used to conduct a pre- and post-outplacement survey of dental
      students and a twice-yearly survey of all MOHP-based clinical supervisors. Paper
      questionnaires were used to survey adult clients and caregivers of child clients
      that the students treated. Data were analysed descriptively and thematically.
      MAIN OUTCOME MEASURES: 68 (61%) of the 112 eligible students completed the pre-
      and post-outplacement questionnaires; 31 clinical supervisor questionnaire
      responses were received representing all six MOHPs; and 426 client and 130
      caregiver questionnaire responses were received from five MOHPs. RESULTS: 79% of
      students felt well prepared for outplacement and 75% indicated that they would
      consider working for a MOHP in future. Of the clinical supervisors, 93% indicated
      that the students were adequately prepared for outplacement, and 68%, that they
      would recommend one or more students for employment. However, 58% associated the
      outplacements with decreased productivity. More than 97% of adult clients and
      caregivers of child clients were pleased with the care that the students
      provided. CONCLUSION: Recommendations for strengthening the outplacement
      programme included: increasing communication between the Faculty, MOHPs and
      students; addressing the financial cost of the programme to the MOHPs; and
      providing more support for clinical supervisors.

PMID- 25845057
TI  - An exploratory study of parental knowledge of early childhood oral health care in
      Southland, New Zealand.
AB  - OBJECTIVES: The primary objective was to clearly assess the oral health care
      knowledge of Southland parents. The secondary objective was to identify whether
      inequalities exist between parents with different ethnicity, education or income.
      DESIGN: An exploratory study based on a simple online/ paper questionnaire.
      SETTING: Participants were recruited through Southland early childcare centres.
      Researchers contacted 115 centres, 66 agreed to participate and 58 returned
      questionnaires. METHODS: Questionnaires were distributed to each centre to be
      completed by the parents. The questionnaire was able to be completed online or as
      a paper copy. Centres were supplied with dental brochures, which were distributed
      after the questionnaires were returned. Questionnaires were collated and the
      responses analysed. RESULTS: Six hundred and seventy questionnaires were
      returned, 213 online and 457 paper copies. The typical participant was a mother
      (93.9%), age 34 years (median), a non-smoker (86.3%), non-Maori (87.1%), with a
      university degree (33.9%) and an annual household income between $60,001 and
      $100,000 (36.5%). Twenty of the 47 questions were selected to reflect parental
      knowledge. Overall, 65.1% of the respondents answered all 20 questions correctly.
      Differences in knowledge were identified between mothers and other participants
      (65.4% vs. 59.4%), smokers and non-smokers (61.3% vs. 65.7%), Maori and non-Maori
      (61.6% vs. 65.6%) and education level (Primary 58.0% vs. Degree 68.7%) (P <
      0.05). CONCLUSIONS: This study revealed differences in knowledge in early
      childhood oral health care. Participants who identified as non-mothers (fathers,
      step-fathers, legal care givers or other), smokers, Maori or low education
      displayed significantly less knowledge. Further education and oral health care
      promotion may be needed to improve this disparity.

PMID- 25845058
TI  - The impact of patient's complaints on New Zealand dentists.
AB  - BACKGROUND AND OBJECTIVES: This study aimed to investigate the impact of
      receiving a patient complaint on dentists in New Zealand. METHOD: A qualitative
      research method was chosen to investigate the experience of dentists in receipt
      of a complaint. Nine dentists practising in New Zealand who had received
      complaints from a variety of sources were interviewed. All volunteered having
      responded to requests and advertisements seeking participants for the study. In
      depth interviews with line-by-line transcript analysis allowed the discovery of
      themes and subthemes related to the impact of complaints. RESULTS: Receiving a
      complaint was a stressful experience for these dentists. Anxiety, loss of
      confidence, fear of loss of income and altered relationships with complainants
      characterised respondents' personal responses. Dentists were distracted from
      family time by the complaint, and their families experienced upset and anxiety.
      Anxiety spread within the practice to colleagues and staff. Respondents and their
      staff had to cope with difficult and at times abusive behaviour from complainants
      and their families. Dentists reported feeling helpless, struggling with lack of
      timeliness, the need for a satisfactory and meaningful resolution and the impact
      of third parties, particularly in the genesis of the complaint. They were aware
      of costs incurred by patients. They sought meaningful support but sometimes late
      in the process. For these respondents the complaint led to few changes in their
      practice. CONCLUSION: Receiving a complaint is a stressful experience and
      dentists need appropriate emotional as well as legal support. The responsibility
      for this lies with the wider profession.

PMID- 25845059
TI  - The Securinega alkaloids.
AB  - Securinega alkaloids represent a family of plant secondary metabolites known for
      50 years. Securinine (1), the most abundant and studied alkaloid of this series
      was isolated by Russian researchers in 1956. In the following years, French and
      Japanese scientists reported other Securinega compounds and extensive work was
      done to elucidate their intriguing structures. The homogeneity of this family
      relies mainly on its tetracyclic chemical backbone, which features a butenolide
      moiety (cycle D) and an azabicyclo[3.2.1]octane ring system (rings B and C).
      Interestingly, after a period of latency of 20 years, the Securinega topic
      reemerged as a prolific source of new natural structures and to date more than 50
      compounds have been identified and characterized. The oligomeric subgroup
      gathering dimeric, trimeric, and tetrameric units is of particular interest. The
      unprecedented structure of the Securinega alkaloids was the subject of extensive
      synthetic efforts culminating in several efficient and elegant total syntheses.
      The botanical distribution of these alkaloids seems limited to the Securinega,
      Flueggea, Margaritaria, and Breynia genera (Phyllanthaceae). However, only a
      limited number of plant species have been considered for their alkaloid contents,
      and additional phytochemical as well as genetic studies are needed. Concerning
      the biosynthesis, experiments carried out with radiolabelled aminoacids allowed
      to identify lysine and tyrosine as the precursors of the piperidine ring A and
      the CD rings of securinine (1), respectively. Besides, plausible biosynthetic
      pathways were proposed for virosaine A (38) and B (39), flueggine A (46), and
      also the different oligomers flueggenine A-D (48-51), fluevirosinine A (56), and
      flueggedine (20). The case of nirurine (45) and secu'amamine (37) remains elusive
      and additional studies seem necessary to understand their mode of production. The
      scope of biological of activities of the Securinega alkaloids was mainly centered
      on the CNS activity of securinine (1), although the exact mechanism of action
      remained in part unknown. Nevertheless, for its stimulant and antispasmodic
      effects securinine nitrate was marketed as a drug in the USSR until the early
      1990s. Moreover, securinine (1) and several other Securinega alkaloids recently
      demonstrated promising anticancer properties. In particular securinine (1)
      demonstrated markedly benefits in the treatment of acute myeloid leukemia.

PMID- 25845060
TI  - The homalium alkaloids: isolation, synthesis, and absolute configuration
      assignment.
AB  - The structurally related natural products (-)-homaline, (-)-hopromine, (-)
      hoprominol, and (-)-hopromalinol have been collectively termed the homalium
      alkaloids. All four alkaloids possess bis-zeta-azalactam structures, but differ
      only by the identities of the side chain on each lactam ring. Since their
      isolation (from the leaves of Homalium pronyense Guillaum found in the forests of
      New Caledonia), there have been several syntheses of homaline, hopromine,
      hoprominol, and hopromalinol in both racemic and enantiopure forms. The most
      highly yielding and versatile strategy for their synthesis employs the conjugate
      addition of an enantiopure lithium amide reagent to an alpha,beta-unsaturated
      ester as the key stereodefining step. This methodology has been used in the
      syntheses of all four members of the homalium alkaloid family and their
      stereoisomers.

PMID- 25845061
TI  - The alkaloids of the madangamine group.
AB  - This chapter is focused on madangamines, a small group of complex diamine
      alkaloids isolated from marine sponges of the order Haplosclerida, and covers
      their isolation, characterization, biogenesis, biological activity, and
      synthesis. Structurally, madangamines are pentacyclic alkaloids with an
      unprecedented skeletal type, characterized by a common diazatricyclic core and
      two peripheral macrocyclic rings. The isolation of these alkaloids from
      Xestospongia ingens (madangamines A-E) and Pachychalina alcaloidifera
      (madangamine F) is described in detail. Physical and complete spectroscopic 1H
      and 13C NMR data are included. The proposed biogenesis of madangamines from
      ammonia, a functionalized three-carbon unit, and saturated or unsaturated linear
      long-chain dialdehydes, via partially reduced bis-alkylpyridine macrocycles, is
      discussed. The synthesis of alkaloids of the madangamine group has been little
      explored, with only one total synthesis reported so far, that of (+)-madangamine
      D. This review also describes several model synthetic approaches to the
      diazatricyclic ABC core of these alkaloids, as well as model studies on the
      construction of the (Z,Z)-unsaturated 11-membered E macrocycle common to
      madangamines A-E, the 13- and 14-membered D rings of madangamines C-E, and the
      all-cis-triunsaturated 15-membered D ring of madangamine A. Some members of this
      group have shown significant in vitro cytotoxicity against a number of cancer
      cell lines.

PMID- 25845062
TI  - The Veratrum and Solanum alkaloids.
AB  - This survey on steroidal alkaloids of the Veratrum and Solanum family isolated
      between 1974 and 2014 includes 187 compounds and 197 references. New developments
      in the chemistry and biology of this family of natural products with a special
      focus on the medicinal relevance of the jervanine alkaloid cyclopamine are
      discussed.

PMID- 25845063
TI  - Alkaloids of the Annonaceae: occurrence and a compilation of their biological
      activities.
AB  - This chapter presents an overview of the chemistry and pharmacology of the
      alkaloids found in species of the Annonaceae family. The occurrence of alkaloids
      from Annonaceae species, as well as their chemical structures and pharmacological
      activities are summarized in informative and easy-to-understand tables. Within
      the Annonaceae family, the genera Annona, Duguetia, and Guatteria have led to
      many important publications. Valuable and comprehensive information about the
      structure of these alkaloids is provided. The alkaloids of the aporphine type
      represent the predominant group in this family. Many of the isolated alkaloids
      exhibit unique structures. In addition to the chemical structures, the
      pharmacological activities of some alkaloids are also presented in this chapter.
      Thus, the leishmanicidal, antimicrobial, antitumor, cytotoxic, and antimalarial
      activities observed for these alkaloids are highlighted. The chapter is presented
      as a contribution for the scientific community, mainly to enable the search for
      alkaloids in species belonging to the Annonaceae family.

PMID- 25845064
TI  - Integrated community case management of sick children in Ethiopia. Foreword.

PMID- 25845065
TI  - Introduction to a special supplement: delivering integrated community case
      management to treat childhood illness at scale in Ethiopia.

PMID- 25845066
TI  - Integrated community case management of childhood illnesses: adaptations for the
      developing regions of Ethiopia.

PMID- 25845067
TI  - From integrated community case management to community-based newborn care.

PMID- 25845068
TI  - Can training health extension workers in the integrated pharmaceutical logistics
      system (IPLS) be effective, affordable, and opportunistic?

PMID- 25845069
TI  - How do Ethiopia's health extension workers spend their time?

PMID- 25845070
TI  - National scale-up of integrated community case management in rural Ethiopia:
      implementation and early lessons learned.
AB  - BACKGROUND: Although under-five mortality in Ethiopia has decreased 67% in the
      past two decades, many, children still die from preventable or treatable
      conditions, mainly pneumonia, newborn problems, diarrhea, malaria and
      malnutrition. Most of these deaths can be avoided with timely and appropriate
      care, but access to and use of treatment remains inadequate. Community health
      workers, appropriately trained, supervised, and supplied with essen- tial
      equipment and medicines, can deliver case management or referral to most sick
      children. In 2010, Ethiopia added pneumonia to diarrhea, malaria and severe acute
      malnutrition, targeted for treatment in the integrated community case management
      (iCCM) strategy. PURPOSE: This article describes the national scale-up of iCCM
      implementation and early lessons learned. METHODS: We reviewed data related to
      iCCM program inputs and processes from reports, minutes, and related documents
      from January 2010 through July 2013. We describe introduction and scale-up
      through eight health system components. RESULTS: The government and partners
      trained and supplied 27,116 of the total 32,000 Health Extension Workers and
      mentored 80% of them to deliver iCCM services to over one million children. The
      government led a strong-iCCM partnership that attracted development partners in
      implementation, monitoring, evaluation, and research. Service utilization and
      weak supply chain remain-major challenges. CONCLUSION: Strong MOH leadership,
      policy support, and national partnerships helped successful national iCCM scale
      up and should help settle remaining challenges.

PMID- 25845071
TI  - Performance of Ethiopia's health system in delivering integrated community-based
      case management.
AB  - BACKGROUND: Analyzing complex health programs by their components and sub
      components serves design, documentation, evaluation, research, and gap
      identification and prioritization. In 2012, we developed a rapid methodology to
      characterize integrated community case management (iCCM) programs, by assessing
      benchmarks for eight health system components in three program phases. OBJECTIVE.
      To assess iCCM benchmarks in Ethiopia three years after scale-up commenced, and
      to compare the benchmarks across the geographical region. METHODS. Six national
      iCCM experts scored each of 70 benchmarks (no, partial, or yes) and then were
      facilitated to reach consensus. RESULTS. Overall, iCCM benchmark achievement in
      Ethiopia was high (87.3%), highest for pre-introduction (93.0%), followed by
      introduction (87.9%) and scale-up (78.1%) phases. Achievement by system component
      was highest for coordination and policy (94.2%) and lowest for costing and
      finance (70.3%). Six regional, countries benchmark assessments, including two
      from Ethiopia 14 months apart, were highly correlated with program duration at
      scale (correlation coefficient: +0.88). CONCLUSION: Ethiopia has a mature, broad
      based iCCM program. Despite limitations, the method described here rapidly,
      systematically, and validly characterized a complex program and highlighted areas
      for attention through government or partners.

PMID- 25845072
TI  - Coverage and equitability of interventions to prevent child mortality in rural
      Jimma and West Hararghe Zones, Oromia Region, Ethiopia.
AB  - BACKGROUND: Interventions to prevent childhood illnesses are important components
      of the Ethiopian Health Extension Program (HEP). Although the HEP was designed to
      reduce inequities in access to health care, there is little evidence on
      equitability of preventive interventions in Ethiopia. PURPOSE: This article
      describes coverage of preventive interventions and how many interventions
      individual children received We also examined which factors were associated with
      the number of preventive interventions received, and assessed the extent to which
      interventions were equitably distributed. METHODS: We conducted a cross-sectional
      survey in 3,200 randomly selected households in the rural Jimma and West Hararghe
      Zones of Ethiopia's Oromia Region. We calculated coverage of 10 preventive
      interventions and a composite of eight interventions (co-coverage) representing
      the number of interventions received by children. Mul- tiple linear regressions
      were used to assess associations between co-coverage and explanatory variables.
      Finally, we assessed the equitability of preventive interventions by comparing
      coverage among children in the poorest and the least poor wealth quintiles.
      RESULTS: Coverage was less than 50% for six of the 10 interventions. Children
      received on average only three of the eight interventions included in the co
      coverage calculation. Zone, gender, caretaker age, religion, and household wealth
      were all significantly associated with co-coverage, controlling for key
      covariates. Exclusive breastfeeding, vaccine uptake, and vitamin A
      supplementation were all relatively equitable. On the other hand, coverage of
      insecticide-treated nets or indoor residual spraying (ITN/IRS) and access to safe
      water were significantly higher among the least poor children compared to
      children in the poorest quintile. CONCLUSION: Coverage of key interventions to
      prevent childhood illnesses is generally low in Jimma and West Hararghe. Although
      a number of interventions were equitably distributed, there were marked wealth
      based inequities for interventions that are possessed at the household level,
      even among relatively homogeneous rural communities.

PMID- 25845073
TI  - Utilization of integrated community case management services in three regions in
      Ethiopia after two years of implementation.
AB  - BACKGROUND: The integrated community case management (iCCM) strategy has brought
      fully integrated treatment for sick children to the community in Ethiopia since
      2010. OBJECTIVES: To describe patterns of use of iCCM services in 31 woredas
      (districts) in three regions of Ethiopia. METHODS: We analyzed all 60,452
      encounters (58,341 [98.2%] for children 2-59 months of age and 2079 [1.8%] for
      children < 2 months of age) recorded in iCCM registration books from December 24,
      2012 to January 15, 2013 in 622 randomly sampled health posts. RESULTS: Children
      2-23 months constituted more than half (58.9%) of the total children treated, and
      about half of the registered infants < 2 months (1000/2079 [48.1%]) were not sick
      since some Health Extension Workers (HEWs) were recording well-infant visits. On
      average, sick children had 1.3 symptoms, more among children 2-59 months than
      among young infants (1.4 vs. 1.04, respectively). The main classifications for
      children 2-59 months were diarrhea with some or no dehydration (29.8%), pneumonia
      (20.7%), severe uncomplicated malnutrition (18.5%), malaria (11.2%), and other
      severe diseases (4.0%). More than half the sick children < 2 months (52.7%) had
      very severe disease. Treatment rates (per 1000 children per year) were low for
      all classifications: 11.9 for malaria (in malarious kebeles only), 20.3 for
      malnutrition, 21.2 for pneumonia, and 29.2 for diarrhea with wide regional
      variations, except for pneumonia. Nearly two-thirds of health posts (64%) treated
      <= 5 cases/month, but one treated 40. Health Extension Workers saw 60% more sick
      children 2-59 months in the third quarter of 2012 than in the third quarter of
      2011. CONCLUSION: The use of iCCM services is low and increasing slowly, and the
      few busy health posts deserve further study. Recording healthy young infants in
      sick registers complicates tracking this vulnerable group.

PMID- 25845074
TI  - Effect of the health extension program and other accessibility factors on care
      seeking behaviors for common childhood illnesses in rural Ethiopia.
AB  - BACKGROUND: In January 2011, Health Extension Workers (HEWs) of Ethiopia's Health
      Extension Program (HEP) began providing pneumonia case management for children
      less than five years of age through the integrated Community Case Management
      (iCCM) strategy. OBJECTIVE: To report the effect of HEP, following the
      introduction of iCCM, and other accessibility factors on care-seeking behaviors
      for common childhood illnesses (acute respiratory infection [ARI], diarrhea, and
      fever). METHODS: Three possible care-seeking outcomes for childhood illnesses
      were considered: not seeking appropriate care, seeking care from HEP sources, or
      seeking care from other appropriate sources. The baseline care-seeking outcomes
      from the Ethiopian Demographic and Health Survey, 2011, were compared with the
      care-seeking outcomes in a follow-up iCCM survey in December 2012. The effects of
      the HEP intensity and other factors on care-seeking outcomes were estimated using
      regression analyses. RESULTS: Appropriate care-seeking for children with acute
      respiratory infection, ARI, diarrhea, or fever increased two-fold, from 19% at
      baseline to 38% at follow-up, mainly due to an increase in seeking care for
      common child- hood illnesses from HEWs. Higher intensity of the HEP and other
      accessibility factors were associated with higher care-seeking for childhood
      illnesses from HEP sources. CONCLUSION: Incorporating iCCM within the HEP service
      package significantly improved the appropriate care-seeking behaviors for
      childhood illnesses in rural Ethiopia.

PMID- 25845075
TI  - Effectiveness of supportive supervision on the consistency of integrated
      community cases management skills of the health extension workers in 113
      districts of Ethiopia.
AB  - BACKGROUND: Consistency in the adherence to integrated Community Case Management
      (iCCM) protocols for common childhood illnesses provided by Ethiopia's Health
      Extension Program (HEP) frontline workers. One approach is to provide regular
      clinical mentoring to the frontline health workers of the HEP at their health
      posts (HP) through supportive supervision (SS) following the initial training.
      OBJECTIVE: To Assess the effectiveness of visits to improve the consistency of
      iCCM skills (CoS) of the HEWs in 113 districts in Ethiopia. METHODS: We analyzed
      data from 3,909 supportive supervision visits between January 2011 and June 2013
      in 113 districts in Ethiopia. From case assessment registers, a health post was
      classified as consistent in managing pneumonia, malaria, or diarrhea cases if the
      disease classification, treatment, and follow-up of the last two cases managed at
      the health posts were consistent with the protocol. We used regression models to
      assess the effects of SS on CoS. RESULTS: All HPs (2,368) received at least one
      supportive supervision visit, 41% received two, and 15% received more than two.
      During the observation period, HP management consistency in pneumonia, malaria,
      and diarrhea increased by 3.0, 2.7 and 4.4-fold, respectively. After controlling
      for secular trend and other factors, significant dose-response relationships were
      observed between number of SS visits and CoS indicators. CONCLUSIONS: The SS
      visits following the initial training were effective in improving the CoS.

PMID- 25845076
TI  - Effect of performance review and clinical mentoring meetings (PRCMM) on recording
      of community case management by health extension workers in Ethiopia.
AB  - BACKGROUND: The Performance Review and Clinical Mentoring Meeting (PRCMM) is an
      approach to improve and sustain Health Extension Worker (HEW) skills and
      performance in integrated Community Case Management (iCCM). OBJECTIVE: To compare
      HEW performance in recording case management before and after they participated
      in PRCMM. METHODS: We conducted a historical cohort analysis of iCCM case records
      between September 2010 and December 2012 from 622 randomly selected health posts
      representing 31 intervention woredas (districts) of Amhara, Oromia and Southern
      Nations Nationalities and Peoples' Regions. We used longitudinal regression
      analysis comparing the trend in the consistency of the classification with the
      assessment, treatment and follow-up date as well as caseload in the periods
      before and after PRCMM, with 5511 and 7901 case records, respectively. RESULTS:
      Overall consistency improved after PRCMM for all common classifications as
      follows: pneumonia (54.1% [95% CI: 47.7%-60.5%] vs. 78.2% [73.9%-82.5%]), malaria
      (50.8% [42.9%-58.7%] vs. 78.9% [73.4%- 84.4%]), and diarrhea (33.7% [27.9%-39.5%]
      vs. 70.0% [64.7%-75.3%]). This improvement was consistently observed comparing
      the six months before and the six months after PRCMM in all the common
      classifications except for malaria where the improvement observed during the
      first three post-PRCMM months disappeared during the fifth and sixth months.
      Caseload increased significantly after PRCMM (6.6 [95% CI: 5.9-7.3] vs. 9.2 [8.5
      9.9] cases/health post/month). CONCLUSION: PRCMM seemed to improve iCCM
      performance of HEWs and should be integrated within the PHC system and given
      about every six months, at least at first, to sustain improvement.

PMID- 25845077
TI  - Integrated community case management: quality of care and adherence to medication
      in Beneshangul-Gumuz Region, Ethiopia.
AB  - BACKGROUND: The International Rescue Committee (IRC) supports implementation of
      integrated Community Case Management (iCCM) in all 20 woredas (districts) of
      Benishangul Gumuz Region (BSG) in Ethiopia. OBJECTIVES: To identify the gaps in
      the provision of quality iCCM services provided by Health Extension Workers
      (HEWs) and to assess caregivers' adherence to prescribed medicines for children
      under five years of age. METHODS: We conducted a cross-sectional descriptive
      study with both quantitative and qualitative study methods. We interviewed 233
      HEWs and 384 caregivers, reviewed HEW records of 1,082 cases, and organized eight
      focus groups. RESULTS: Most cases (98%) seen by HEWs were children 2-59 months
      old, and 85% of the HEWs did not see any sick young infant. The HEWs' knowledge
      on assessments and classification and need for referral of cases was above 80%.
      However; some reported challenges, especially in carrying out assessment
      correctly and not checking for danger signs. Over 90% of caretakers reported
      compliance with HEWs' prescription. CONCLUSION: Partners have successfully
      deployed trained HEWs who can deliver iCCM according to protocol; however,
      additional support is needed to assure a supply of medicines and to mobilize
      demand for services, especially for young infants.

PMID- 25845078
TI  - Quality and use of IMNCI services at health center under-five clinics after
      introduction of integrated community-based case management (ICCM) in three
      regions of Ethiopia.
AB  - BACKGROUND: The Integrated Management of New born and Childhood Illness (IMNCI)
      and the related Integrated Community Case Management (iCCM) are evidence-based
      strategies to reduce childhood mortality in Ethiopia at health centres and
      community health posts, respectively. The effect of introducing iCCM on IMNCI is
      not known. OBJECTIVE: To assess the caseload and quality of lMNCI service in
      under-five clinics in health centres after iCCM implementation. METHODS: This
      cross-sectional study used register review to assess the IMNCI service use
      (before and after iCCM, in 2010 and 2012, respectively) and quality throughout
      the period in randomly selected health centers in three regions of the Integrated
      Family Health Program (Oromia, SNNPR [Southern Nations and Nationalities and
      Peoples Region] and Tigray). RESULTS: Caseload of sick children at 28 health
      centers increased by 16% after iCCM implementation (21,443 vs. 24,882 children in
      2010 and 2012, respectively. The consistency of IMNVCI treatment with
      classification for pneumonia, diarrhea and malaria was low (78, 45, and 67%,
      respectively) compared to iCCM treatment (86, 80, and 91%, respectively).
      CONCLUSION: Health center case load increased modestly after iCCM was introduced,
      but was lower than expected, even when combined with health post use from other
      studies. The demand strategy for sick children needs review. The quality of IMNCI
      needs improving even to bring it to the quality of iCCM at health posts, as
      measured by the same methods. Successful quality assurance approaches from iCCM,
      e.g., the Performance Review and Clinical Mentoring Meeting, could be adapted for
      IMNCI.

PMID- 25845079
TI  - Effect of integrated community case management of common childhood illnesses on
      the quality of malaria case management provided by health extension workers at
      health posts.
AB  - INTRODUCTION: The Integrated Family Health Program supported the government of
      Ethiopia to implement the Integrated Community Case Management (iCCM) strategy to
      control childhood illness of which malaria is a major cause. OBJECTIVE: To assess
      the effect of ICCM training on quality of malaria case management at health
      posts. METHODS: . A comparative cross-sectional study was conducted among 170
      Health Extension Workers (HEW) providing either integrated or vertical malaria
      case management for children less than five years of age in 14 woredas
      (districts) of West Hararghe Zone using a multi-stage sampling procedure. HEWs in
      seven intervention woredas were trained in malaria case management and rapid
      diagnostic test (RDT) procedures through iCCM, and HEWs in comparison woredas
      were trained vertically through the national malaria control program. Performance
      was assessed using interview, review of registers, and observation of RDT
      procedure. RESULTS: Intervention HEWs performed better than their counterparts in
      correct drug prescription (90.8 vs. 81.0%, p = 0.03), treatment duration (97.7
      vs. 89.9%, p = 0.001), and treatment schedule (95.4 vs. 75.9%, p = 0.000).
      Intervention HEWs recorded case management with more consistency than their
      counterparts (>= 80% consistency between: classification and assessment [23.0 vs.
      3.8%; p = 0.000], classification and treatment [24.1 vs. 7.6%; p = 0.003], and
      classification and follow up [24.1% vs. 0.0%; p = 0.000]); however, there is room
      for improvement. CONCLUSION: ICCM training has a positive effect on the quality
      of malaria case management at the community level.

PMID- 25845080
TI  - Factors influencing the low utilization of curative child health services in
      Shebedino District, Sidama Zone, Ethiopia.
AB  - BACKGROUND: Use and coverage of curative interventions for childhood pneumonia,
      diarrhea, and malaria were low in Ethiopia before integrated community-based case
      management (iCCM). OBJECTIVES: To examine factors accounting for low use of
      iCCMin Shebedino District applying a "Pathway to Sur- vival" approach to assess
      illness recognition; home care; labeling and decision-making; patterns of care
      seeking; access, availability and quality of care; and referral. METHODS: Shortly
      after introduction of iCCM, we conducted five studies in Shebedino District in
      May 2011: a population-based household survey; focus group discussions of mothers
      of recently ill children; key informant in- terviews, including knowledge
      assessment, with Health Extension Workers at health posts and with health workers
      at health centers; and an inventory of drugs, supplies, and job aids at health
      posts and health centers. RESULTS: The many barriers to use of evidence-based
      treatment included: (1) home remedies of uncertain effect and safety that delay
      care-seeking; (2) absent decision-maker; (3) fear of stigma; (4) expectation of
      non-availability of service or medicine; (5) geographic and financial barriers;
      (6) perception of (or actual) poor quality of care; and (7) accessible,
      available, affordable, reliable, non-standard, alternative sources of care.
      CONCLUSION: Only a system-strengthening approach can overcome such manifold
      barriers to use of curative care that has not increased much after ICCM
      introduction.

PMID- 25845081
TI  - Assessment of the monitoring and evaluation system for integrated community case
      management (ICCM) in Ethiopia: a comparison against global benchmark indicators.
AB  - BACKGROUND: Program managers require feasible, timely, reliable, and valid
      measures of iCCM implementation to identify problems and assess progress. The
      global iCCM Task Force developed benchmark indicators to guide implementers to
      develop or improve monitoring and evaluation (M&E) systems. OBJECTIVE: To
      assesses Ethiopia's iCCM M&E system by determining the availability and
      feasibility of the iCCM benchmark indicators. METHODS: We conducted a desk review
      of iCCM policy documents, monitoring tools, survey reports, and other rele- vant
      documents; and key informant interviews with government and implementing partners
      involved in iCCM scale-up and M&E. RESULTS: Currently, Ethiopia collects data to
      inform most (70% [33/47]) iCCM benchmark indicators, and modest extra effort
      could boost this to 83% (39/47). Eight (17%) are not available given the current
      system. Most benchmark indicators that track coordination and policy, human
      resources, service delivery and referral, supervision, and quality assurance are
      available through the routine monitoring systems or periodic surveys. Indicators
      for supply chain management are less available due to limited consumption data
      and a weak link with treatment data. Little information is available on iCCM
      costs. CONCLUSION: Benchmark indicators can detail the status of iCCM
      implementation; however, some indicators may not fit country priorities, and
      others may be difficult to collect. The government of Ethiopia and partners
      should review and prioritize the benchmark indicators to determine which should
      be included in the routine M&E system, especially since iCCMdata are being
      reviewed for addition to the HMIS. Moreover, the Health Extension Worker's
      reporting burden can be minimized by an integrated reporting approach.

PMID- 25845082
TI  - Modeling potential reduction of child mortality after national scale-up of
      community-based treatment of childhood illnesses in Ethiopia.
AB  - BACKGROUND: Since 2010, 28,000 female health extension workers (IEWs) received
      training and support to provide integrated community based case management (iCCM)
      of childhood pneumonia, diarrhea, malaria, and se- vere malnutrition in Ethiopia.
      OBJECTIVE: We conducted a modeling exercise using two scenarios to project the
      potential reduction of the under five mortality, riate due io the iCCM program in
      the four agrarian regions of Ethiopia. METHODS. We created three projections: (1)
      baseline projection without iCCM; (2) a "moderate" projection using 2012 coverage
      data scaled up to 30% by 2015 and (3) a "best case" scenario scaled up to 80%
      with 50% of newborns with sepsis receiving effective treatment by 2015. RESULTS.
      If the 2012 coverage gains (moderate projection) were applied to the four
      agrarian regions, we project that the iCCM program could have saved over 10,000
      additional lives per year among children age 1-59 months. If iCCM coverage
      reaches the, "best case" scenario, nearly 80,000 additional lives among children
      1-59 months of age would be saved between 2012 and 2015. CONCLUSION. High quality
      iCCM, delivered and used at scale, is an important contributor to the reduction
      of under five mortality in rural Ethiopia. Continued investments in iCCM are
      critical to sustaining and improving recent declines in child mortality.

PMID- 25845083
TI  - Costing commodity and human resource needs for integrated community case
      management in thie differing community health strategies of Ethiopia, Kenya and
      Zambia.
AB  - BACKGROUND: To ensure correct and appropriate funding is available, there is a
      need to estimate resource needs for improved planning and implementation of
      integrated Community Case Management (iCCM). OBJECTIVE: To compare and estimate
      costs for commodity and human resource needs for iCCM, based on treatment
      coverage rates, bottlenecks and national targets in Ethiopia, Kenya and Zambia
      from 2014 to 2016. METHODS: Resource needs were estimated using Ministry of
      Health (MoH) targets fronm 2014 to 2016 for implementation of case management of
      pneumonia, diarrhea and malaria through iCCM based on epidemiological,
      demographic, economic, intervention coverage and other health system parameters.
      Bottleneck analysis adjusted cost estimates against system barriers. Ethiopia,
      Kenya and Zambia were chosen to compare differences in iCCM costs in different
      programmatic implementation landscapes. RESULTS: Coverage treatment rates through
      iCCM are lowest in Ethiopia, followed by Kenya and Zambia, but Ethiopia had the
      greatest increases between 2009 and 2012. Deployment of health extension workers
      (HEWs) in Ethiopia is more advanced compared to Kenya and Zambia, which have
      fewer equivalent cadres (called commu- nity health workers (CHWs)) covering a
      smaller proportion of the population. Between 2014 and 2016, the propor- tion of
      treatments through iCCM compared to health centres are set to increase from 30%
      to 81% in Ethiopia, 1% to 18% in Kenya and 3% to 22% in Zambia. The total
      estimated cost of iCCM for these three years are USD 75,531,376 for Ethiopia, USD
      19,839,780 for Kenya and USD 33,667,742 for Zambia. Projected per capita expen-
      diture for 2016 is USD 0.28 for Ethiopia, USD 0.20 in Kenya and USD 0.98 in
      Zambia. Commodity costs for pneumonia and diarrhea were a small fraction of the
      total iCCM budget for all three countries (less than 3%), while around 80% of the
      costs related to human resources. CONCLUSION: Analysis of coverage, demography
      and epidemiology data improves estimates of fimding requirements for iCCM.
      Bottleneck analysis adjusts cost estimates by including system barriers, thus
      reflecting a more accurate estimate of potential resource utilization. Adding
      pneumonia and diarrhea interventions to existing large scale community-based
      malaria case management programs is likely to require relatively small and
      nationally affordable investments. iCCM can be implemented for USD 0.09 to 0.98
      per capita per annum, depending on the stage of scale-up and targets set by the
      MoH.

PMID- 25845084
TI  - A descriptive study of the changes in coverage of preventive and promotive
      interventions before and after the introduction of integrated community case
      management (ICCM) in Ethiopia.
AB  - BACKGROUND: The effect of integrated community case management (iCCM) of common
      childhood illness on use of vital preventive services is not known. OBJECTIVE: To
      measure the coverage of maternal and child health preventive and promotive
      interventions before and after scaling up iCCM. METHODS: In 2011 and 2013, we
      conducted cross-sectional, population-based, household coverage surveys in four
      Integrated Family Health Program target regions: Amhara, Oromia, SNNP, and
      Tigray. RESULTS: Coverage increased for 10 of 15 indicators, mainly for maternal,
      immunization, and nutrition services. In some cases, we observed dramatic
      increases, i.e., for >= 4 antenatal care visits, antenatal iron and folate, and
      exclusive breastfeeding. Some increase occurred even when 2011 levels were
      already high, i.e., for immunization. Three indicators remained high and
      unchanged (bednet ownership, children sleeping under bednets, and any latrine).
      Two indicators decreased (tetanus toxoid and households with >= 2 bednets).
      CONCLUSION: Scale-up of iCCM was consistent with increased coverage of most
      preventative and promotive interventions, which may contribute to the life-saving
      effect of iCCM.

PMID- 25845085
TI  - Illness recognition, home care, and care-seeking for sick infants less than two
      months of age in Shebedino District, Sidama Zone, Ethiopia.
AB  - BACKGROUND: The incidence of newborn and young infant health danger signs is
      unknown in Ethiopia. Neverthe- less, experience shows that care-seeking is far
      lower than conservative morbidity estimates would project. OBJECTIVES: To examine
      illness recognition, home care, decision-making, and care-seeking for sick
      infants less than two months of age in Shebedino District, Southern Nations,
      Nationalities and Peoples Region in 2011. METHODS: Focus group interviews of
      mothers (n = 60) of recently ill children. RESULTS: Mothers reported recognizing
      many, but not all, evidence-based newborn danger signs. Home care ranged from
      probably harmless to harmful and delayed definitive care-seeking. Decision-making
      was widespread, but patterns of care-seeking rarely led to prompt, evidence-based
      care. Mothers reported 10 barriers to care- seeking at health posts: lack of
      knowledge about availability of curative services, fear of evil eye, social
      stigma, perceived financial barrier, perceived young infant fragility, an elder's
      contrary advice, distance, husband's re- fusal, fear of injection, and belief in
      recovery without medicine. CONCLUSION: Young infants are more vulnerable to
      illness than their older counterparts, yet they are less likely to receive the
      care they need without a targeted, contextualized communication strategy to
      generate demand for case management services that are accessible, available, and
      of good quality.

PMID- 25845086
TI  - Conclusions: delivering integrated community case management (ICCM) to treat
      childhood illness at scale in Ethiopia.

PMID- 25845087
TI  - [Left ventricular assist device: which emotional impact on the patient?].
AB  - BACKGROUND: Advanced heart failure is a challenging disease; the implantable Left
      Ventricular Assist Device (L-VAD) is becoming a good chance for relieving
      symptoms and prolong survival in most CHF patients. The emotional impact of L-VAD
      implantation is thought to be high but, at present, published data are scant
      about that. Aim of this study was to evaluate the modifications of perceived
      quality of life (QoL) in a group of patients recently treated with L-VAD
      implantation, admitted to a residential cardiac rehabilitation program, and to
      compare the results to those obtained in patients awaiting heart transplantation
      and recently transplanted. MATERIAL AND METHOD: We enrolled 66 patients (pts)
      with a recent implant of L-VAD, 51 with refractory heart failure awaiting heart
      transplantation (HT) and 55 recently treated with HT. On day two after admission,
      all patients underwent a complete psychometric assessment consisting in the
      compilation of: Minnesota Living with Heart Failure Questionnaire (MLHFQ). Beck
      Anxiety Inventory (BAI). Beck Depression Inventory-II (BDI-II). RESULTS: L-VAD
      recipients had significantly higher scores at MLHFQ. Both the total score and the
      2 subscales scores (respectively physical and emotional disturbances) were
      statistically significant when compared with post-transplant patients.
      Posttransplant pts had the lowest scores regarding anxiety symptoms, while the
      bearers of device had the highest ones. The same results were obtained for
      depression scores (BDI-II), both in total score and in the subscales (somatic
      symptoms and affective symptoms). CONCLUSIONS: With an opening scoring, this
      study showed the development of more relevant psychological troubles in patients
      treated with L-VAD when compared to those awaiting for heart transplantation and
      those transplanted.

PMID- 25845088
TI  - Exercise training reduces high mobility group box-1 protein levels in women with
      breast cancer: findings from the DIANA-5 study.
AB  - PURPOSE: To determine whether exercise training might exert anti-inflammatory
      effect by reducing HMGB1 levels in women with breast cancer (BC). METHODS: We
      analyzed monocentric data from the DIANA (DIET AND ANDROGENS)-5 PROJECT. Study
      population consisted of 94 patients randomized into two groups: 61 patients (53
      +/- 8 yrs, training group) were assigned to a structured exercise training
      intervention (3 times/week for the first 3 months, and once /week for the
      following 9 months); whereas 33 patients (52 +/- 7 yrs, control group) followed
      only the general indications to adhere to the life-style intervention suggestions
      of the DIANA protocol. At study entry and after 12 months, all patients underwent
      cardiopulmonary exercise testing, biochemical as- sessment [HMGB1, high
      sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6)]; and lipid and
      glycemic profile. RESULTS: There were no significant differences between groups
      in baseline clinical and inflammatory profile. Among the training group, only
      19/61 patients had high adherence to the exercise intervention. After stratifying
      the study population according to the level of adhesion to the exer- cise
      intervention, 1-year HMGB1 levels were lower among patients more adherent to
      exercise (p for trend = 0.001). Further adjusting for age, body mass index and
      baseline values, 1-year HMGB1 levels remained significantly and inversely
      associated to the level of adhesion to the exercise intervention (B = -0.97, SE =
      0.43, p = 0.01). CONCLUSIONS: Moderate intensity exercise training in BC
      survivors is associated with reduced HMGB1 levels that are proportional to the
      level of adhesion to the exercise intervention, independently from other
      classical inflammatory molecules, suggesting an exercise-induced anti
      inflammatory effect mediated by HMGB1.

PMID- 25845089
TI  - [Cardiologic evaluation of patients undergoing chemotherapy].
AB  - Life expectancy in patients affected by cancer has recently increased because of
      early diagnosis and actual therapies. In recent years, Oncology and Cardiology
      developed a tight relationship because of common risk factors (i.e., obesity,
      smoking, alcool intake, etc...), and for preventing the prothrombotic status due
      to cancer and the potential cardiotoxicity of chemotherapy. Cardiotoxicity
      incidence is reported from 1% up to 70% in retrospective analyses of drug
      protocols, mainly representing by left ventricular dysfunction (both reversible
      or irreversible), but also by arrhythmias, hypertension, atrioventricular block,
      coronary spasm, and arterial or venous thromboembolism. The early detection of
      the chemoterapy induced cardiotoxicity is now mandatory and can be obtained
      through a proper patients selection for different treatments and a strict
      monitoring during the follow-up period. The role of biomarkers of early cardiac
      damage, mainly, troponin I and brain natriuretic peptide-BNP, has been recently
      challenged, and algorithms are currently available. In the present paper, we
      propose how to perform a cardiological evaluation of patients undergoing
      chemotherapy tailored by the known adverse effects of the drugs.

PMID- 25845090
TI  - Neurocognitive profile of patients with continuous flow left ventricular assist
      device.
AB  - The increase of severe heart failure and the consequent reduction of the organ
      availability for transplantation has led to, in recent years, the introduction of
      the LVAD as replacement therapy to heart transplantation. Severe Heart Failure
      patients show cognitive deficits in various domains especially in executive
      functions, memory and speed of proceedings, due to different
      neurophysiopathological processes including chronic hypoperfusion and subsequent
      damage to hippocampal and para-hippocampal cortical areas. It is also known that
      these deficits improve after heart transplantation. We carried out a literature
      review selecting studies that analyzed the cognitive changes in patients with
      severe heart failure after implantation of the Continuous Flow Left Ventricular
      Assist Device. According to the inclusion criteria, we selected four studies
      since 2005 that presented a comprehensive neurocognitive assessment. The results
      show that the cognitive profile, with the implantation of LVAD improves in memory
      and executive domains, and this improvements results stable in short-medium time.
      The effects would also be independent of the type of flow produced by the device
      (pulsatile vs continuous). We believe that further studies are required to
      explore the relationship between LVAD and cognitive function in severe heart
      failure.

PMID- 25845091
TI  - [Erectile dysfunction and cardiovascular disease: focus on].
AB  - Erectile dysfunction (ED) is a common clinical problem and its prevalence
      increases in frequency with age. ED is a risk marker for major cardiovascular
      events independently of other more common risk factors in men with and without
      known cardiovascular disease. On the basis of the "artery-size hypothesis"
      patients with cardiovascular disease often report ED before disease detection, in
      average 3 years. Thus, by an early identification of ED, the cardiol- ogist is
      given a unique opportunity to better assess the cardiovascular risk of each
      patient. Although there is a general impression that ED has an important
      predictive role, its diagnosis in clinical practice is widely suboptimal owing to
      misconceptions from the side of the patient and a suboptimal management of the
      personal relationship from the side of the physician. This paper explores the
      critical connection between ED and cardiovascular disease and evaluates how this
      association may influence clinical practice.

PMID- 25845092
TI  - [Familial hypercholesterolemia in cardiac rehabilitation: a new field of
      interest].
AB  - Familial hypercholesterolemia (FH) is a frequently undiagnosed genetic disease
      characterized by substantial elevations of low-density lipoprotein cholesterol
      (LDL-C). The prevalence of heterozygous FH (HeFH) in the general population is
      1:500 inhabitants, while the prevalence of homozygous FH (HoFH) is 1:1,000,000.
      If FH is not identified and aggressively treated at an early age, affected
      individuals have a 20-fold increased lifetime risk of coronary heart disease
      compared with the general population. This narrative review provide a concise
      overview of recommendations for diagnosis and treatment of adults and children
      with FH, and discuss the utility of considering FH as a comorbidity at the entry
      of cardiac rehabilitation programmes.

PMID- 25845093
TI  - [The Health Department of Sicily "Regional recommendations for hospital discharge
      and communication with patients after admission due to a cardiologic event"
      decree].
AB  - Mortality and rehospitalizations still remain high after discharge for an acute
      cardiologic event. In this context, hospital discharge represents a potential
      pitfall for heart disease patients. In the setting of care transitions, the
      discharge letter is the main instrument of communication between hospital and
      primary care. Communication, besides, is an integral part of high-quality,
      patient-centered interventions aimed at improving the discharge process.
      Inadequate information at discharge significantly affects the quality of
      treatment compliance and the adoption of lifestyle modifications for an effective
      secondary prevention. The Health Department of Sicily, in 2013, established a
      task force with the aim to elaborate "Regional recommendations for hospital
      discharge and communication with patients after admission due to a cardiologic
      event", inviting to participate GICR-IACPR and many other scientific societies of
      cardiology and primary care, as discharge letter and communication are
      fundamental junctions of care transitions in cardiology. These recommendations
      have been published as a specific decree and contain: a structured model of
      discharge letter, which includes all of the parameters characterizing patients at
      high clinical risk, high thrombotic risk and low risk according to the Consensus
      document ANMCO/GICR-IACPR/GISE; is thus possible to identify these patients,
      choosing consequently the most appropriate follow-up pathways. A particular
      attention has been given to the "Medication Reconciliation" and to the
      identification of therapeutic targets; an educational Kit, with different forms
      on cardiac diseases, risk factors, drugs and lifestyle; a check-list about
      information given to the patient and caregivers. The "Recommendations" represent,
      in conclusion, the practical realization of the fruitful cooperation between
      scientific societies and political-administrative institutions that has been
      realized in Sicily in the last years.

PMID- 25845094
TI  - [Physiotherapists education and competences for cardiac rehabilitation].
AB  - Authors show a summary of educational programs in physiotherapy at the present
      time in Italy, just regarding cardiac rehabilitation, treated usually too shortly
      and in a not homogenous way between the various academic awarding institution and
      suffering for the italian general educational system misaligned with the others
      European partners. They presents, according with ICF rules and with accreditated
      organization, the essential competences required for that health professional to
      deal with accountability needs and problems in cardiac rehabilitation, with
      enphasis about the low appeal of the discipline by the physiotherapist even
      though her great epidemiologic relevance.

PMID- 25845095
TI  - An unusual case of myocardial infarction.
AB  - Myocardial infarction may be the result of embolism of calcified material from
      the aortic valve or thrombotic formations adhering to the same. We report a case
      of late myocardial infarction secondary to embolization from a thrombus adherent
      to the aortic valve jutting out in the ostium of the left main coronary artery.

PMID- 25845096
TI  - [Aneurysmatic aortic root in bicuspid aortic valve stenosis: mini-invasive
      approach with sutureless prosthesis].
AB  - The implantation of sutureless bioprosthesis is currently not recommended in
      patients affected by bicuspid aortic valve because lacking data and follow up. We
      report the first case of a patient affected by bicuspid aortic valve stenosis and
      aneurysm of non coronary sinus of Valsalva that underwent a successful
      substitution of aneurysmatic sinus and minimal invasive sutureless implantation.

PMID- 25845097
TI  - [In defense of the specialty].

PMID- 25845098
TI  - [Endoscopic incision of intravesical ureteroceles in patients with duplex
      system].
AB  - PURPOSE: To evaluate the clinical status and renal function of pa- tients with
      duplex system and intravesical ureterocele after drainage by cystoscopy. MATERIAL
      AND METHODS: In 9 patients with duplex system and intravesical ureterocele
      drainage was performed to present recurrent urinary tract infections (7 children
      with episodes of pyelonephritis and sepsis) or obstruction of the urinary
      drainage. The mean age was 33 months (range 8-108 months). The thecnique was done
      under general anesthesia in the operating room and puncture of the ureterocele
      was performed using cystourethroscopy with loop electrode. The minimum follow-up
      was 12 months (range 12-48 months) and includes renal ultrasound, renal isotopic
      study (Mag3 with furosemide) and-echocystography study in patients with
      preoperative vesicoureteral reflux or postoperative urinary tract infection.
      RESULTS: The average operative time was 60 minutes. Mean hospital stay was 48
      hours. There were no complications during the procedure. In five patients urinary
      infection episodes disappeared. Ultrasound demonstrated decreased hydronephrosis
      and megaureter. In two patients the differential renal function following the
      technique improved. One patient with preoperative split renal function of 14%
      required nephrectomy. One patient had postoperative vesicoureteral reflux.
      CONCLUSIONS: The drainage of intravesical ureterocele in patients with duplex
      system reduces episodes of urinary tract infection and urinary tract dilation.

PMID- 25845099
TI  - [Vascular rings, our experience with 18 cases].
AB  - AIM: Vascular rings are a rare cause of compression of the trachea and/or the
      esophagus, causing stridor and/or severe dysphagia. We present our experience in
      the diagnosis and management of vascular rings. METHODS: Retrospective study in
      which we analyzed clinical history, diagnosis and management of 18 patients
      diagnosed with vascular ring between January 1985 and December 2013. We evaluate
      endoscopy as a diagnostic method. RESULTS: A total of 18 patients were included,
      with a median age of 2 years. 83.3% (15/18) had some type of symptom: 46.7%
      (7/15) had respiratory symptoms such as respiratory distress, stridor, recurrent
      respiratory infections, bronchospasm with wheezing or asthma in older children;
      20% (3/15) had digestive symptoms such as dysphagia, vomiting and regurgitation;
      and 33.3% (5/15) combined respiratory and digestive symptoms. The remaining
      patients, 16.7% (3/18) were asymptomatic and the diagnosis was casual. The most
      common types of vascular rings were double aortic arch (27.8%) and aberrant
      subclavian right artery (27.8%). In 3 cases (16.7%) a Kommerell diverticulum was
      associated. 44.4% (n = 8) was operated on, the remaining did not present symp-
      toms which justify the intervention (n = 10). 37.5% of patients had postoperative
      complications (iatrogenic recurrent paralysis and persistent tracheomalacia).
      There was no mortality in our series. The median follow-up was 6.4 years. At the
      moment, 88.9% of patients are asymptomatic, and 33.3% have been definitely
      discharged. CONCLUSIONS: Vascular rings are rare, and usually presented with
      common symptoms in childhood. Therefore, in front of a longstanding and recurrent
      respiratory symptoms, or dysphagia, we should think of a vascular ring. Not all
      subjects are candidates for surgical correction; therefore a multidisciplinary
      evaluation is essential.

PMID- 25845100
TI  - [Quality of life and long term results in Hirschsprung's disease].
AB  - INTRODUCTION: The most frequent long term side effects of Hirschsprung's disease
      (HD) surgery are obstructive problems and fecal incontinence. In this study, we
      analyse long term functional results of the two most used surgical techniques
      (Duhamel-D- and De la Torre-dlT-) from the patient's point of view, through
      quality of life and functionality questionnaires. METHODS: We selected short
      segment HD patients >= 4 years) that were operated in our unit from 1996 until
      2011. We employed two validated questionnaires: Bowel Function Score (BFS) and
      Gastrointestinal Quality of Life Index (GIQLI). Both questionnaires were also
      tested in two control age matched groups, each for every arm (controlD or control
      dlT). RESULTS: Among 28 preselected patients, 22 (78.6%) answered both
      questionnaires. Group D (10 patients) showed more constipation: 60% vs. 16.7% ( p
      = 0.01). Patients in group dlT (12 patients) showed more leaks: 58.3 vs. 10% (p =
      0.03). Results of both questionnaires were higher (better) in Group D: 16 vs.
      12.8 points (BFS, p = 0.007) and 74.1 vs. 69.8 (GIQLI, p = 0.17). The control
      group showed an overall better scores than HD patients: 17.2 vs. 14.3 (BFS p =
      0.001) and 75.9 vs. 71.8 (GIQLI, p = 0.04). Separately, both groups of patients
      showed worse scores when compared with each control group. DISCUSSION: Our
      results are similar to other studies, where global scores of functional results
      and quality of life are worse in operated HD patients than in age matched
      controls. Fecal incontinence has more impact on social scores than constipation.
      Due to the fact that our dlT patients have more frequently fecal leaks, their
      scores are worse than in the D group. Nevertheless, patients in dlT group are
      younger and may improve their results as they get older, as it is often the case
      in operated HD patients.

PMID- 25845101
TI  - [Cervico-sternotomy for thoracic inlet conditions in children].
AB  - BACKGROUND/AIM: Neither cervicotomy nor postero-lateral thoracotomy allow safe
      surgical access to the lower cervical spine and high posterior mediastinum with
      full control of the vascular and neural structures involved. We report our
      favorable experience with cervico-sternotomy for accessing this region. PATIENTS
      AND METHODS: Six patients were operated upon between 1998 and 2011 for either
      removal of huge cervico-thoracic neural ganglioneuromas (n = 2) or anterior
      arthrodesis for congenital (n = 2), neuropathic (n = 1) or osteolytic scoliosis
      (n = 1). In all cases, cervicotomy was followed by sternotomy, thymectomy,
      division of the innominate vein and dissection of jugular veins, carotid arteries
      and vagus nerves. RESULTS: The tumors measured 10.9 x 3.9 x 8.7 cm and 8 x 6 x 5
      cm, and involved the paravertebral chain from the aortic arch to the base of the
      skull and from the left lung hilus to the thyroid region respectively. In the
      scoliosis patients, anterior vertebral fixation between C5 and T5 was readily
      feasible. Blood transfusion was avoided. Horner's syndrome and transient
      lymphedema were the only complications. Median operative time was 210 minutes
      (range 180-240 minutes) and median estimated blood loss was 2.7 cc/kg (0-13.8
      cc/kg). Median hospital stay was 7 days (range 5-18 days). CONCLUSIONS: Cervico
      sternotomy is an optimal approach for this anatomical region in children. It
      offers better exposure of the anterior cervico-thoracic spine and the thoracic
      inlet than cervicotomy or thoracotomy. Control of the nervous and vascular
      structures was safely achieved in all cases and postoperative discomfort was
      surprisingly limited.

PMID- 25845102
TI  - [Kidney transplantation in children weighing 11 kg or less].
AB  - AIMS OF THE STUDY: To evaluate the outcome of kidney transplantation in children
      with low weight. METHODS: Retrospective review of the medical records of patients
      weighing 11 kg or less that received kidney transplantation between 2001 and 2013
      were retrospectively reviewed. RESULTS: Fifty-nine kidney transplantations were
      performed in pediatric patients in our center, 12 of them were performed in
      patients weighing 11 kg or less (20%). The mean age of the recipient at the time
      of transplantation was 2 years (1-3.5); the mean weight was 9.4 +/- 1.1 kg (8.3
      11). The etiology of kidney failure was malformative in 42% of patients,
      inherited in 33%, glomerular in 8% and oiler etiologies in 17% of the patients.
      Two patients did not receive replacement therapy before transplantation (16.7%),
      nine received peritoneal dialysis (75%) and one of them hemodialysis (8.3%).
      Eleven of the grafts were from cadaveric donor (91.7%) and one of them from a
      living donor (8.3%). The mean donor age was 10 years (0.5-29). There was one case
      of acute graft thrombosis (8.3%) and one case of eventration requiring
      reoperation; there were no other major complications. Mean follow-up was 59
      months (4-130). Overall survival (OS) was 100% at 1 year and 91.7% at 5 years.
      There was one death in a patient with mitochondrial disease with a functioning
      graft. Graft survival (GS) was 92% at 1 year and 75% at 5 years. CONCLUSION:
      Kidney transplantation is the treatment of choice for end-stage kidney failure in
      the young child. It provides good results in terms of patient and graft survival.

PMID- 25845103
TI  - [Therapeutic approach in urinary tract stones in children].
AB  - PURPOSE: Kidney stone disease in children is a rare pathology, with a low
      incidence in Spain (1/4,500 hospitalized children). The spontaneous expulsion
      rate is about 34-47% which means that more of 50% of children need active
      treatment. Paediatric patients forming urinary stones have a high risk of
      recurrence, therefore, a standard diagnosis and treatment are needed. We present
      our experience in urolithiasis treatment in children. MATERIALS AND METHODS: We
      reviewed retrospectively all the patients <= 16 years hospitalized in our
      hospital with urolithiasis diagnosis from 2000 to 2013, citing treatment
      modality, stone-free rates and complications. RESULTS: A total of 69 patients
      with a mean age of 8,2 years (range 1-16 years) were treated in our hospital
      during that period. The main clinical presentation was pain (52%). The diagnosis
      was made by abdominal ultrasounds in all cases. About localization, 21 lithiasis
      were found in distal urether (UD), 8 in medium urether (UM), 3 in proximal
      urether (UP) and 13 in renal pelvis (PR). The mean size was 13 mm. 21 (30%)
      patients had a spontaneous expulsion of the stone, 14 (20%) patients were treated
      with extracorporeal shock wave lithotripsy and in 22 (32%) patients the elected
      therapy was ureterosopic stone fragmentation (n = 13) or removal (n = 9). No
      complications were observed. The overall stone-free rate was 79% (n = 55).
      CONCLUSIONS: Kidney stone disease in children is a rare pathology, with its own
      features about diagnosis and treatment, which requires medical care in a
      specialized center. The optimal treatment should be considered regarding the age
      of the patient, localization and size of the stone, as well as the team
      experience.

PMID- 25845104
TI  - [Complicated omental cyst after a herniorrhaphy in an infant].
AB  - Omental cysts are uncommon benign masses localized in the abdomen. This article
      describes the case of a male infant who underwent surgery due to a left inguinal
      hernia. During the operation a small omental cyst was found inside the sac that
      was resected. The first postoperative days were uneventful but the infant came
      back to hospital seven days after. Subsequent imaging and operative findings
      revealed a complicated omental cyst. This cyst was removed and the histopathology
      report described an inflammatory pseudotumor. The postoperative evolution was
      satisfactory and the patient has remained asymptomatic since he was discharged
      from hospital. In conclusion, it is important to explore the contents of the
      hernial sac during inguinal hernia repair. The finding of a small omental cyst
      inside the sac should encourage to study other potential intraabdominal lesions.

PMID- 25845105
TI  - [Autoamputated ovarian cysts. A clinical case].
AB  - INTRODUCTION: Autoamputation refers to a situation in which a tubo-ovarian
      remnant is found free-floating in the abdomino-pelvis, which is a complication of
      fetal ovarian cyst causing ovarian torsion in uterus. There have been only 13
      reported cases of ovarian autoamputation involving children under 1 years of age.
      CLINICAL CASE: We present the case of a 9-month old female with history of
      abdominal mass in the 26th week of gestation, who was referred to the pediatric
      surgery department with CT findings in an abdominal tumor and negative physical
      examination, in laparoscopic examination cystic mass is 6 cm in diameter and no
      left ovary. The histopathological examination confirmed an ovarian cyst with
      necrotic and hemorrhagic remaining. COMMENTATION: This case is reported because
      of the low incidence of pathology, exceptional presentation and the favorable
      outcome of the patient with implemented laparoscopic management.

PMID- 25845106
TI  - [Human tail: rare lesion with occult spinal dysraphism].
AB  - Human tails can be classified as either true tails or pseudotails. True human
      tails are rare clinical entities. We describe a newborn with a midline sacral
      cutaneous appendage. Magnetic resonance imaging of the lumbosacral area revealed
      occult spinal dysraphism with tethered cord and intradural lipoma. Prenatal
      diagnosis of left renal agenesis was confirmed on postnatal evaluation. Surgical
      excision of the appendage was performed and histopathological examination
      demonstrated a true tail. The child recovered uneventfully and has been
      asymptomatic for 3 years. Dorsal cutaneous appendages are a marker of underlying
      occult spinal dysraphism and requires detailed neuroimaging investigation in
      order to prevent irreversible neurological damaged.

PMID- 25845107
TI  - [Conservative treatment for omental infarction].
AB  - The omental infarction is a pathology that occurs more and more in children due
      to the increased use of imaging studies and the increment in overweigth and
      obesity. Clinical presentation is characterized by abdominal pain and can be
      confused with appendicitis, ileitis, adenitis, among other abdominal conditions.
      Definitive diagnosis requires the performance of radiologic investigations and
      its treatment may be conservative. We report three cases of omental infarction
      with different form of clinical presentation, successfully managed
      conservatively.

PMID- 25845108
TI  - [Nursing home residents are underserved in dental health care. The greater the
      disability status, the greater the care deficit].

PMID- 25845109
TI  - [Why did I get upset?].

PMID- 25845110
TI  - [Our experts explain... Emin concept - not a remedy].

PMID- 25845111
TI  - [Looking over the shoulder].

PMID- 25845112
TI  - [Diffusing crisis situations with intervention].

PMID- 25845113
TI  - [Nurses as survival experts].

PMID- 25845114
TI  - [Nurse led versus physician led care of asthma patients].

PMID- 25845115
TI  - [Tackling the shortage of skilled personnel. Nursing care facilities of Vivantes
      Forum for Seniors GmbH educates Vietnamese in geriatric nursing care].

PMID- 25845116
TI  - [Spouses as caregivers].

PMID- 25845117
TI  - [Four types of students].

PMID- 25845118
TI  - [Needs of the elderly in communities. Uncovering nursing fields].

PMID- 25845119
TI  - [Nursing care during imprisonment: report of experiences and reflections. Eight
      months in prison in Italy].

PMID- 25845120
TI  - [US president Roosevelt tried to hide the sequelae of his polio infection].

PMID- 25845121
TI  - [From GPS orientation devices to sensor mats].

PMID- 25845122
TI  - Introduction. Consensus oral anticoagulants: special emphasis on vitamin K
      antagonists.

PMID- 25845124
TI  - Recommendations for oral anticoagulants.

PMID- 25845123
TI  - Anticoagulant agents.

PMID- 25845125
TI  - Current Indian scenario on the use of oral anticoagulants.

PMID- 25845126
TI  - Monitoring oral anticoagulation therapy.
AB  - Although VKAs are often criticised for the need of frequent monitoring, such a
      practice is very beneficial. Recommended 12-weekly monitoring, rather than 4
      weekly, in patients with consistently stable INRs may help reduce patient
      inconvenience. The recommended use of patient self-management of anticoagulation
      in motivated and competent patients is further very helpful. In the absence of
      laboratory test and antidotes to reverse their effects, the use of NOACs is quite
      challenging.

PMID- 25845127
TI  - Oral anticoagulation in special population and conditions.

PMID- 25845128
TI  - A long way off. 1940.

PMID- 25845129
TI  - Education saves lives.

PMID- 25845130
TI  - Evaluation of a social marketing campaign to increase awareness of immunizations
      for urban low-income children.
AB  - OBJECTIVE: To assess community awareness of childhood immunizations and intent to
      immunize children after a social marketing immunization campaign. METHODS: We
      used 2 interviewer-assisted street-intercept surveys to evaluate awareness of
      childhood immunizations and intent to immunize low-income children. The "Take
      Control! Immunize" social marketing campaign was developed using a community
      based participatory research approach and used billboards, flyers, and various
      "walking billboard" (eg, backpacks, pens) to deliver immunization messages in the
      community settings. RESULTS: Over 85% of community members recalled the "Take
      Control! Immunize" message. Almost half of those who saw the immunization message
      indicated that the message motivated them to act, including getting their
      children immunized or calling their physician to inquire about their children's
      immunizations status. All respondents indicated that immunizations were important
      for children and that they were likely or very likely to immunize their children.
      Respondents who reported that "Take Control!" messages motivated them to act in
      the first intercept survey were significantly more likely than those in the
      second intercept to report being likely or very likely to immunize their
      children. CONCLUSION: Culturally appropriate social marketing immunization
      messages in targeted urban settings can increase parental awareness and
      behavioral intention to immunize children.

PMID- 25845131
TI  - Factors that affect rate of INR decline after warfarin discontinuation.
AB  - BACKGROUND: Despite vast literature on warfarin, optimal strategies for
      temporarily discontinuing and restarting warfarin have not been established. To
      improve warfarin discontinuation processes, we investigated known medical and
      genetic factors that influence stable warfarin dose to determine how well they
      predict the time until patients become subtherapeutic after discontinuing
      warfarin. METHODS: This was a retrospective cohort study of patients who
      temporarily discontinued warfarin before an elective procedure andhad at least 2
      international normalized ratio (INR) values available during the discontinuation
      period. Data abstracted included date of discontinuation, warfarin dose, INR
      values, body surface area, gender, age, indication for warfarin, current
      medications, eGFR, and presence of bridging therapy with heparin. DNA variants
      were tested in CYP2C9, VKORC1, and CYP4F2 genes. Subjects were excluded if they
      received vitamin K, fresh frozen plasma, or prothrombin complexes to reverse
      anticoagulation. Asymptotic regression models were used to approximate decline in
      INR during warfarin clearance. Spearman correlations and Kruskal-Wallis tests
      were used to characterize associations of model estimates with quantitative
      variables and for group comparisons, respectively. RESULTS: Other than the
      expected association with baseline INR, correlations of model parameter estimates
      with clinical variables were generally weak and not statistically significant.
      The strongest associations with slope were with serum creatinine and eGFR. There
      were no significant associations with CYP2C9, VKORC1, or CYP4F2 DNA variants, but
      there were few subjects combined in the nonwild groups for CYP2C9. Estimated
      slope showed moderate correlation with observed dose. CONCLUSION: Known clinical
      and genetic predictors of therapeutic dose were not found to be strongly
      associated with the slope of INR decline after warfarin discontinuation.

PMID- 25845132
TI  - Increased patient communication using a process supplementing an electronic
      medical record.
AB  - BACKGROUND: Importance: Patients with cervical cytology abnormalities may require
      surveillance for many years, which increases the risk of management error,
      especially in clinics with multiple managing clinicians. National Committee for
      Quality Assurance (NCQA) Patient-Centered Medical Home (PCMH) certification
      requires tracking of abnormal results and communicating effectively with
      patients. OBJECTIVES: The purpose of this study was to determine whether a
      computer-based tracking system that is not embedded in the electronic medical
      record improves (1) accurate and timely communication of results and (2) patient
      adherence to follow-up recommendations. METHODS: Design: Pre/post study using
      data from 2005-2012. Intervention implemented in 2008. Data collected via chart
      review for at least 18 months after index result. Participants: Pre-intervention:
      all women (N = 72) with first abnormal cytology result from 2005-2007. Post
      intervention: all women (N = 128) with first abnormal cytology result from 2008
      2010. Patients were seen at a suburban, university-affiliated, family medicine
      residency clinic. Intervention: Tracking spreadsheet reviewed monthly with
      reminders generated for patients not in compliance with recommendations. Main
      Outcome and Measures: (1) rates of accurate and timely communication of results
      and (2) rates of patient adherence to follow-up recommendations. RESULTS:
      Intervention decreased absent or erroneous communication from clinician to
      patient (6.4% pre- vs 1.6% post-intervention [P = 0.04]), but did not increase
      patient adherence to follow-up recommendations (76.1% pre- vs 78.0% post
      intervention [ P= 0.78]). CONCLUSIONS: Use of a spreadsheet tracking system
      improved communication of abnormal results to patients, but did not significantly
      improve patient adherence to recommended care. Although the tracking system
      complies with NCQA PCMH requirements, it was insufficient to make meaningful
      improvements in patient-oriented outcomes.

PMID- 25845133
TI  - Coronary dissection in a patient with essential thrombocytosis.
AB  - A 50-year-old man was admitted to the hospital with left shoulder and arm
      discomfort. He had no recent history of change in his energy level, limitations
      to activity, exertional chest pain, or shortness of breath. He had cardiac risk
      factors, including a strong family history of pre-mature coronary artery disease
      and dyslipidemia. He had a syncopal episode in 2003 with a positive troponin I,
      but had a negative cardiac workup, including cardiac catheterization that showed
      luminal irregularities and no significant coronary artery disease. An
      echocardiogram was performed to rule out potential cardiac causes for shoulder
      pain and showed regional wall motion abnormalities. Follow-up cardiac
      catheterization revealed left anterior descending artery proximal and mid
      dissection and a long area of dissection in the first diagonal branch. Laboratory
      evaluation showed significant platelet elevation and positive JAK2 study.
      Ultrasound of the abdomen revealed moderate splenomegaly. The enlarged spleen,
      positive JAK2 study, and persistently elevated platelet count confirmed the
      diagnosis of essential thrombocythemia. Essential thrombocythemia can predispose
      individuals to vascular dysfunction and damage, which may contribute to coronary
      artery dissection. With this case, we propose that essential thrombocythemia
      should be excluded in the presence of coronary dissection and thrombocytosis.

PMID- 25845134
TI  - [Codon optimization of hemagglutinin as a promising tool for improving of the
      influenza vaccines immunogenicity].
AB  - Modification of the codon bias of sequences is a promising tool of the gene
      expression control. The theoretical basis of the codon optimization is reviewed,
      data on experiments in changing the viral gene codon bias for purposes of vaccine
      development are discussed. Research into the field of the influenza vaccine
      immunogenicity improvement with codon optimization method is reviewed. Prospects
      of the use of the codon optimization technique for influenza vaccine development
      are considered.

PMID- 25845135
TI  - [The ability of the natural ketones to interact with bacterial quorum sensing
      systems].
AB  - The effect of the natural ketones emitted by bacteria (2-nonanone, 2-heptanone, 2
      undecanone) on the functioning of the Quorum Sensing (QS) systems was studied. In
      this work, three lux-reporter strains containing the components of the LasI/LasR,
      RhlI/RhlR, LuxI LuxR QS systems were used as biosensors for the N-acyl-homoserine
      lactones. It was shown that at concentrations of ketones that exhibited little or
      no bactericidal action the ketones could modulate the QS-response by suppressing
      the expression of the lux-operon reporter to a greater extent than the cell
      viability of these strains.

PMID- 25845136
TI  - [The genome polymorphism of the Mycobacterium avium subsp. hominissuis strains].
AB  - The non-tuberculosis mycobacteria Mycobacterium avium subsp. hominissuis (MAH)
      are able to cause human mycobacteriosis. In this work, the results of the first
      comprehensive study of the genome polymorphism of the clinical strains of MAH
      were reported using the typing scheme by 13 loci MATR-VNTR (TR292, TRX3, TR25,
      TR47, MATR-1, MATR-4, MATR-5, MATR-6, MATR-8, MATR-11, MATR-14, MATR-15, MATR-16)
      containing tandem nucleotide sites and IS1245-RFLP-typing sites. A total of 90
      MAH strains isolated from patients with lung mycobacteriosis without
      epidemiological connection (including HIV infected) were tested in 2008-2011. The
      inhomogeneity of the MAH strains by 36 profiles of 13 loci MATR-VNTR was
      observed. The majority of the strains (68.8%) were included in the 8 MATR-VNTR
      clusters; most large cluster contained 37 strains with 13-bitnumerical profile
      2222223145443'. The nucleotide sequence of the MATR-16 (3') locus contains the
      long deletion (GenBank accession no. KF479191). The MAH strains of the MATR-VNTR
      clusters were found to be inhomogeneous by the IS1245 marker. The MATR-VNTR
      typing method by 13 loci is recommended for preliminary differentiation of
      domestic MAH strains with further analysis of the MATR-VNTR clusters using the
      IS1245-RFLP-typing method.

PMID- 25845137
TI  - [A single-tube real-time RT-PCR assay for the RNA detection and quantification of
      genetically diverse HIV Including rare non-M group of the HIV-1 and HIV-2].
AB  - The RT-PCR method with real-time fluorescence detection was used for development
      of phi prototype of diagnostic kit for reliable diagnosis of genetic variants of
      RNA of the HIV-1 of groups M, N, O, P and RNA of the HIV-2 in blood plasma and
      serum. The kit is stable against nucleotide defects, provides broad linear range
      of concentration of the HIV RNA, 100% analytical specificity and adequate
      analytical sensitivity: 42 ME/ml (HIV-1 of group M), 45 copies/ml (HIV-2), 92
      copies/ml (HIV-1 of group O), 90 copies/ml (HIV-1 of group N). The kit provided
      successful detection and measurement of HIV RNA concentration in the samples of
      the international reference panel of the HIV-1 genotype. The results of the test
      correlate with results of commercial tests.

PMID- 25845138
TI  - [Crimean-Congo hemorrhagic fever virus in Stavropol region in 2011].
AB  - The genetic analysis of the Crimean-Congo hemorrhagic fever (CCHF) virus
      circulating in Stavropol region during 2011 year was suggested. A total of 14 RNA
      isolates from the Crimean hemorrhagic fever patients were genetically typed. The
      genetic analysis of the CCHF virus stains based on M-segment sequences (positions
      2607-2932) supported the circulation of the genotype Europe 1 in the Stavropol
      region of Russia. In addition to previously known lineage STV-ROS, the second
      lineage VLG/ROS was observed in Stavropol region.

PMID- 25845139
TI  - [Molecular-genetic analysis of the genomes of porcine reproductive and
      respiratory syndrome virus and porcine circovirus type 2 circulating in the area
      of Russian Federation].
AB  - The molecular genetic analysis of the genomes of the virus of porcine
      reproductive respiratory syndrome (VPRRS) and porcine circovirus type 2 (PCV-2)
      circulating in the area of the Russian Federation was discussed. The results of
      this work showed the circulation of the strains of the European genotype VPRRS
      similar to those found in France and Denmark from 1998 to 2001. The homology of
      the fragment of one of the genes between the Russian isolates and the vaccine
      strain Porcilis PRRS (Intervet) was found. It requires further study. The strains
      representing the North American genotype VPRRS were not found. The PCV-2 genomes
      fall into three separate goups. One (genotype 2b) is formed by isolates in
      Malaysia, Brazil, Switzerland, China, Slovakia, UK, USA, isolated during the
      period from 2004 to the present time. The second group consists of sequences of
      the viruses isolated in 2000-2012 in Canada, the U.S., China, and South Korea
      (genotype 2a). The third group is formed by highly pathogenic isolates in 2013
      from China (highly pathogenic genotype 2c). The circulation of all three known
      genotypes of PCV-2: 2a, 2b, and 2c in Russian Federation was demonstrated.

PMID- 25845140
TI  - [Genotypic identification of the bovine leukemia virus].
AB  - Phylogenetic analysis of the sequenced segments of the provirus BLV locus env
      gene and the strategy of the PCR-PDRF-genotyping consistent with phylogenetic
      classification of pathogenic agent and suggested in our works provided taxonomic
      identification of BLV isolates identified in cattle in Tatarstan (Russian
      Federation) as representatives of the 4th, 7th, and 8th BLV genotypes. Of 100
      identified isolates, 64 represent the 4th BLV genotype, 28 representatives of BLV
      belong to cluster of the 7th genotype, whereas the other 8 samples of the
      provirus belong to the new 8th genotype of pathologic agent. The strategy VBL PCR
      PDRF-genotyping suggested in our work on the basis of 5 restriction endonucleases
      (PvuII, SspI, HphI, HaeIII, and BstYI) provided correct genotyping identification
      of the viral pathogen.

PMID- 25845141
TI  - [Prevalence of aortal atherosclerosis in workers underwent occupational
      irradiation].
AB  - The authors evaluated prevalence of aortal atherosclerosis in dependence on
      radiation and non-radiation factors in workers underwent occupational prolonged
      irradiation.The study included 22,377 workers of nuclear industry enterprise
      "Mayak", with verified diagnosis of aortal atherosclerosis. Up to 31th December
      2008, a total of 1,840 aortal atherosclerosis cases were registered in the
      examinees group. Aortal atherosclerosis prevalence appeared to depend reliably on
      sex, age, smoking habit (in males), alcohol consumption (in males) and arterial
      hypertension. Findings are that aortal atherosclerosis prevalence was higher in
      males and females underwent external gamma-irradiation of total dose over 0.5 Gy,
      in males and females underwent internal alpha-irradiation from incorporated
      plutonium of total absorbed radiation dose in liver over 0.025 Gy. Thus, aortal
      atherosclerosis prevalence in workers underwent occupational irradiation de-
      pended both on radiational and non-radiational factors.

PMID- 25845142
TI  - [Prognostic assessment for formation of a group of cardiovascular high risk among
      personnel participating in atomic submarines utilization].
AB  - Ultrasound scanning of main vessels (common carotid, internal carotid, common and
      superficial femoral, posterior tibial arteries) in staffers of shipyard "Nerpa"-
      branch of JSC "Shipbuilding center Zvezdochka" (Snezhnogorsk city Murmansk
      region)--engaged into atomic submarines utilization. Findings are atherosclerotic
      changes in common carotid and common femoral arteries--increased thickness of
      intima-media complex over the reference values or atherosclerotic plaque
      formation. The changes were maximal in a group of males aged over 50 with length
      of service over 25 years. Discriminant analysis helped to suggest a mathematic
      model to forecast cardiovascular diseases in personnel of "Nerpa" shipyard.

PMID- 25845143
TI  - [Medical and hygienic aspects of instrumental supervision system over nuclear
      materials and radioactive substances transport on Russian Federation territory].
AB  - Hygienic evaluation of radiation situation in operation of mobile and stationery
      elements within a project of national system for instrumental supervision over
      nuclear materials and radioactive substances transport, created with a Global
      initiative against nuclear terrorism. Levels of exposure to ionizing radiation of
      the screening complexes appeared to match requirements on radiation safety for
      service personnel and general population.

PMID- 25845144
TI  - [Evaluating psychophysiologic adaptation state in operators of Bilibino nuclear
      power station].
AB  - The study revealed that 60% operators of Bilibino nuclear power station suffer
      from psychosomatic diseases, 41.7% of them are assigned to occupational group of
      workers, and major part of the examinees with psychosomatic diseases (45.82%) are
      aged 41-50, high integral level ofpsychophysiologic adaptation is revealed in 5
      examinees (12.5%), medium integral level--in 12 examinees (30%). Lower integral
      level of psychophysiologic adaptation manifested in decrease in psychophysiologic
      and physiologic levels.

PMID- 25845145
TI  - [Evaluating radiation dose load in medical personnel of radiologic diagnostic
      departments].
AB  - The article deals with materials on radiation hygienic evaluation of radiologic
      diagnostic departments in various medical institutions of Moscow. The studies
      covered work of medical staffers in X-ray examination and in contact with short
      lived isotope generators. The authors outlined the examination types and stages
      with maximal radiation danger. Disimetric information obtained during the study
      helped to calculate values of equivalent, effective doses of radiation for
      medical personnel and maximal potential doses.

PMID- 25845146
TI  - [Comparative analysis of ionizing radiation and xenobiotics influence on
      spermatogenic epithelium and dominant lethal mutations output in laboratory
      animals].
AB  - The study covered state of spermatogenic epithelium and dominant lethal mutations
      output in mice of BALB/c and CBA lines, subjected to total gamma-irradiation and
      in Wistar rats after intraperitoneal injection of potassium bichromate (K2Cr2,O7)
      in small and sublethal doses. The BALB/c line mice under low irradiation dose
      (0.25 Gy) demonstrated stimulation effect on spermatogenic epithelium, but in the
      CBA line mice no such effect was seen. Both mice lines under irradiation of 0.25
      Gy and 1.0 Gy demonstrated increase in pathologic sperm counts and in percentage
      ofpreimplantation embryonal death. In rats, injection of potassium bichromate in
      doses of 0.028 mg/kg and 2.8 mg/kg increased number of micronuclear spermatids,
      larger pathologic sperm counts and percentage of postimplantation deaths. Thus,
      lower general embryonal deaths under radiation exposure is due to preimplantation
      embryonal deaths, under exposure to 6-valent chromium--is due to postimplantation
      losses.

PMID- 25845147
TI  - [Oxidative metabolism in radiation injury].
AB  - The article represents results of studies concerning influence of ionizing
      radiation on experimental animals under absolutely lethal doses of 8 Gy. In
      single total irradiation the rats demonstrate changes in lipoperoxic cascade
      products and suppressed activity of anioxidant defence enzymes in generative
      cells--that causes metabolic disorders.

PMID- 25845148
TI  - [Mathematic evaluation of various factor influence on functional strain in
      military servicemen].
AB  - The article covers mathematic assessment of factors characteristic for draft army
      service on functional strain in draftees. Study objects--draftees aged 18-22
      years. The studies were conducted in the beginning, in the middle and in the
      endof draft army service, and in urban and rural area. The study included
      physiologic and psychometry tests. Findings are that mathematic modeling cannot
      remove methodic errors completely in elaborating the criteria for functional
      strain, evaluation and forecasting the current performance of the draftees.

PMID- 25845149
TI  - [Peculiarities of pilot's perception of flight information presented on on-board
      liquid crystal displays].
AB  - The article deals with results of experimental studies conducted on flight
      testing desk and covering peculiarities of pilot's perception of flight
      information presented on on-board liquid crystal display in dependence on changes
      speed and update rate of the screen. The authors determine frequency
      characteristics of information update rate, that achieve acceptable quality of
      the flight parameters perception in accordance with the changes speed. Vigorous
      maneuvering with high angular velocities of changed parameters of roll and pitch
      causes visual distortions that are connected with poor frequency of information
      update rate, deteriorate piloting quality and can cause flight unsafety.

PMID- 25845150
TI  - [Study of speech characteristics in hearing-impaired pilots for creation of voice
      activated system operating airborne equipment].
AB  - Comparative experimental study covered speech characteristics in speakers with
      normal hearing and pilot speakers with neurosensory deafness. Evaluation criteria
      were duration, speech volume, spectral characteristics of words. Main difference
      of speach in pilot speakers with hearing disorders was higher variability of its
      characteristics.

PMID- 25845151
TI  - [The autonomic system reactivity of airport technical personnel using individual
      protective devices against noise].
AB  - The study covered cardiac rhythm variability and hemodynamic parameters in
      airfield technical personnel under exposure to aviation noise and with use of
      individual protective measures against noise. Individual protective means remove
      unfavorable stressful external effects of noise--that is manifested by more
      stable parameters of sympathetic nervous system activity.

PMID- 25845152
TI  - [Restore the connection...between physician and patient as well].

PMID- 25845154
TI  - [The doctor as a neuro-shaman].

PMID- 25845155
TI  - [Science and Art are they opposites?].

PMID- 25845156
TI  - [The anxiogenic effect on physicians of the "less is more" approach].

PMID- 25845157
TI  - [ In favor of e-cigarette].

PMID- 25845158
TI  - [Against e-cigarette].

PMID- 25845160
TI  - [Autohypnosis].

PMID- 25845159
TI  - [How to disclose a case of dementia in office visit?].

PMID- 25845161
TI  - [Deglutition disorder: what to do?].

PMID- 25845162
TI  - [Neuro-otology for general practitioner].

PMID- 25845163
TI  - [Anti-aging plants: plants to stay young longer].

PMID- 25845164
TI  - [Psychotropic drug prescriptions in presence of comorbities].

PMID- 25845165
TI  - [Last generation anti-thrombotic drugs and cerebral hemorrhage ].

PMID- 25845166
TI  - [Mental competency].

PMID- 25845167
TI  - [Urination disorders in neurologic patients].

PMID- 25845168
TI  - [Syncope: initial diagnosis and risk stratification].

PMID- 25845169
TI  - [Skull abnormalities: diagnosis and treatments].

PMID- 25845170
TI  - [Botulinum toxin in neurorehabilitation-insight in current use and applications].

PMID- 25845171
TI  - [Mental status: potential and limitations].

PMID- 25845172
TI  - [Long-term treatment of restless leg syndrome].

PMID- 25845173
TI  - [Neurological emergency in childhood].

PMID- 25845174
TI  - [Posttraumatic stress disorder].

PMID- 25845175
TI  - [Botulinum toxin in neurorehabilitation-insight in current use and applications].

PMID- 25845176
TI  - [A physician, his patients and alcohol. Forty years of training].

PMID- 25845177
TI  - [Management of HIV/ AIDS in 2015].

PMID- 25845178
TI  - [Multiple sclerosis: when to think of it? How to proceed?].

PMID- 25845179
TI  - [Delirium in palliative home care].

PMID- 25845180
TI  - [Gastro-esophageal reflux in mentally handicapped patients].

PMID- 25845181
TI  - [Endocrine causes of acute confusional state].

PMID- 25845182
TI  - [Depression in aging].

PMID- 25845183
TI  - [Brain food. Importance of nutrition in the prevention and treatment of
      dementia].

PMID- 25845184
TI  - [Psychotic disorders].

PMID- 25845185
TI  - [Dizziness].

PMID- 25845186
TI  - [Computed tomography--magnetic resonance tomography, what and when?].

PMID- 25845187
TI  - [Parkinson disease diagnosis: not so easy...].

PMID- 25845188
TI  - [Electrophysiologic exam at the service of primary care physicians].

PMID- 25845189
TI  - [Statistically significant: what benefit for the patient?].

PMID- 25845190
TI  - [Dying from dementia/ dying with dementia].

PMID- 25845191
TI  - [Cannabis in multiple sclerosis treatment: possibilities and limits].

PMID- 25845192
TI  - [Wheelchair adjustment: practical advice for the family doctor].

PMID- 25845193
TI  - [The sound of Love--Neuroplasticity, singing bowls and deep relaxation for the
      health of future generations].

PMID- 25845194
TI  - [Muscle pain: what should you think?].

PMID- 25845195
TI  - [Age related dehydroepiandrosterone decrease: clinical significance and
      therapeutic interest].
AB  - Dehydroepiandrosterone (DHEA) and its sulfate ester (DHEAS) are the most abundant
      steroids in humans, but their levels fall with age. This decrease has been
      associated with several age related diseases such as falls, osteoporosis,
      depression, atherosclerosis and sexual disorders. Moreover, studies have shown
      positive effects of DHEA administration on several of these disorders, with a
      satisfying safety profile. Unfortunately, DHEA has been too frequently mediatized
      as a "fountain of youths, which was responsible for either inadequate
      prescription, or prescription refusal. Longer studies in large populations should
      help to better define indications, treatment modalities and long-term treatment
      safety.

PMID- 25845196
TI  - [Cystic fibrosis: fifty years of progress. And now what?].

PMID- 25845197
TI  - [Confusion].

PMID- 25845198
TI  - [Cancers explained by "bad luck": a growing controversy].

PMID- 25845199
TI  - [What key words to use to retrieve pertinent articles?].

PMID- 25845200
TI  - [The case of the obscene mural in Clermont-Ferrand university hospital
      residents'room].

PMID- 25845201
TI  - [Neuchatel's hospitals: the government says "stop"].

PMID- 25845202
TI  - [Yasmin pill: federal tribunal rules against the plaintiff].

PMID- 25845203
TI  - [The error in health].

PMID- 25845204
TI  - Synthetic biology and biosecurity.
AB  - This article discusses the conflict fields and legal questions of synthetic
      biology, esp. concerning biosecurity. A respective jurisprudential discussion has
      not taken place yet in Germany apart from few statements and recommendations. But
      in Germany, Europe and the USA, it is generally accepted that a broad discussion
      is necessary. This is esp. true for the question of biosecurity and the possible
      dangers arising from Synthetic Biology.

PMID- 25845205
TI  - [Patents and scientific research: an ethical-legal approach].
AB  - This article aims to review the relationship between patents and scientific
      research from an ethical point of view. The recent developments in the law of
      industrial property led in many cases to patent discoveries, contributions of
      basic science, and laws of nature. This trend, which denies the central
      principles of the discipline, creates disturbances in scientific activity, which
      requires the free movement of knowledge in order to develop their potentialities.

PMID- 25845206
TI  - Governing synthetic biology in the light of the Access and Benefit Sharing
      regulation (ABS).
AB  - Synthetic biology is a change of paradigm, i.e. from the exploitation of natural
      and genetic resources to lab production of biological entities. This transitional
      shift represents a great challenge for developing countries, particularly those
      which host biodiversity, and users of genetic resources, since the latter might
      not be longer required to access to actual genetic resources (tangible genetic
      resources) but rather genetic resources' information (intangible genetic
      resources) in order to replicate those resources in labs. This could mean that
      users of genetic resource would not have to comply with the Convention on
      Biological Diversity (CBD) and its complementary treaty, the Nagoya Protocol,
      known also as the Access and Benefit Sharing regime (ABS). Both international
      instrument demands that States create legal mechanisms to secure access and
      benefit sharing, i.e., users of genetic resources are required to obtain prior
      informed consent (PIC) from host countries of biodiversity and reach mutual
      agreed terms (MATs), in which users and countries agree how to share the benefits
      arise from the utilization of genetic resources. The ABS regime is particularly
      relevant since its implementation at national and regional level has created
      tensions between users of genetic resources and developing countries. This
      situation could lead to users removing interest in the exploitation of genetic
      resources, subsequently, meaning that their focus would move towards technologies
      that rely less on tangible genetic resources, including synthetic biology. This
      papers aim to discuss the scope of the CBD and the Nagoya Protocol in the light
      of synthetic biology and the implications for developing countries.

PMID- 25845207
TI  - The legal fate of biobanks between privacy, IPRs and crisis of a firm. A
      preliminary study on the case of "bio-bankruptcy" .
AB  - In the case of biobank bankruptcy, the current legal framework is not suitable to
      protect the rights of research subjects. In the paper we identify such a gap in
      protection and suggest some remedies to address it.

PMID- 25845208
TI  - Genetic resources, biotech patents and gene ownership.
AB  - Human genetic resources are increasingly considered as ordinary commercial goods,
      but their value and utility go beyond the simple and immediate private profit. In
      contrast to other biological resources, commercial use does not focus upon the
      material itself but rather upon the genetic information it contains. Information
      goods are then usually subject to intellectual property rights, but in the
      biological and life science domains, property rights can have a negative
      influence upon the proper allocation of several goods, including genetic material
      or goods that are related to it. This scenario reflects the facts of recent
      litigations in the United States and Europe. In particular, these lawsuits have
      revived the debate over private ownership and control over genes. Within this
      context, the objective of the paper is to discuss how to recast the traditional
      right to access to and use of biochemical and human genetic material currently
      considered as part of the market framework. Looking beyond the protection of
      traditional public goods, the paper emphasizes the debate around the progressive
      commodification of human genetic resources facilitated by an improper use of
      intellectual property rights. Different scenarios are analyzed to evaluate
      alternative instruments and new regulatory approaches to avoid the private
      appropriation of human genetic resources and other natural assets.

PMID- 25845209
TI  - [Impact of synthetic biology on patent law in view of of European jurisprudence].
AB  - The roots of synthetic biology--the redesign of biological molecules, structures
      and organisms--can be traced to the research developed by Jacques L. Monod and
      Francois Jacob in 1961. This field has undergone significant growth in the past
      ten years and its emergence has raised the question of whether the patent system
      is suitable to protect inventions in emergent areas as synthetic biology. The
      article will analyze the numerous scientific, socio-economic, ethical and legal
      challenges faced by synthetic biology, introducing the European Patent Law
      related to biotechnology as the minimum common framework and considering if more
      changes are needed to adequately protect the inventor rights, while taking into
      account the arrival of a new research culture, characterized by embracing open
      innovation and open-source initiatives. The discussion will review some
      biotechnological patent law cases and summarize questions as whether isolated
      molecules of DNA are eligible for patent or the patentability of living matter,
      under the terms of Directive 98/44/EC. The article will finally consider the
      impact of synthetic biology on the European patent system.

PMID- 25845210
TI  - [How to be prudent with synthetic biology. Synthetic Biology and the
      precautionary principle].
AB  - Synthetic biology is a new discipline that is twofold: firstly it offers the
      promise to pay benefits that can alleviate some of the ills that plague mankind;
      On the other hand, like all technologies, holds risks. Given these, the most
      critical and concerned about the risks, invoke the application of the
      precautionary principle, common in cases where an activity or new technology
      creates risks to the environment and/or human health, but far from universally
      accepted happens to be currently one of the most controversial principles. In
      this paper the question of the risks and benefits of synthetic biology and the
      relevance of applying the precautionary principle are analyzed. To do this we
      proceed as follows. The first part focuses on synthetic biology. At first, this
      discipline is characterized, with special attention to what is novel compared to
      the known as "genetic engineering". In the second stage both the benefits and the
      risks associated with it are discussed. The first part concludes with a review of
      the efforts currently being made to control or minimize the risks. The second
      part aims to analyze the precautionary principle and its possible relevance to
      the case of Synthetic Biology. At first, the different versions and
      interpretations of the principle and the various criticisms of which has been the
      subject are reviewed. Finally, after discarding the Precautionary Principle as an
      useful tool, it is seen as more appropriate some recent proposals to treat
      technologies that take into account not only risks but also their benefits.

PMID- 25845211
TI  - [Law 4/2014, of December 9, amending Law 7/2003 of 20 October, by which research
      in Andalusia with non-viable human pre-embryos for in vitro research is
      regulated, and amending Law 1/ 2007 of 16 March, by which research in cellular
      reprogramming is regulated exclusively for therapeutic ends].

PMID- 25845212
TI  - [Effect of electroacupuncture stimulation of "Housanli" (ST 36) and "Zhongwan"
      (CV 12) on serum leptin and hepatocellular JAK 2-STAT 3 signaling in obese rats].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) stimulation of
      "Housanli" (ST 36) and "Zhongwan" (CV 12) on serum leptin level and expression of
      phosphorylated Janus kinase 2 (p-JAK 2) and phosphorylated signal transducer and
      activator of transcription 3 (p-STAT 3) proteins in the liver tissue of obese
      rats. METHODS: Thirty-two male Wistar rats were randomly divided into control
      group, model group, manual acupuncture (MA) group and EA group (n = 8 in each
      group). The obese model was induced by high fat diet for 8 weeks. MA or EA (20
      Hz, 1.5 V) stimulation was applied to bilateral "Housanli" (ST 36) and "Zhongwan"
      (CV 12) for 20 min, once daily for 4 weeks. The animals' body weight and length
      were recorded, and Lee's index was calculated. Serum leptin level and liver p-JAK
      2 and p-STAT 3 protein expression levels were detected using radioimmunoassay and
      Western blot, respectively. RESULTS: In comparison with the control group, the
      rats' body weight, Lee's index, and serum leptin content were remarkably
      increased in the model group (P<0.05), while hepatocellular p-JAK 2 and p-STAT 3
      protein expression levels were significantly down-regulated in the model group
      (P<0.05). After treatment for 4 weeks, the levels of body weight, Lee's index,
      serum leptin were significantly reduced (P<0.05), and hepatocellular p-JAK 2 and
      p-STAT 3 protein expression in the MA and EA groups were considerably up
      regulated compared with the model group (P<0.05). The effect of EA was apparently
      superior to that of MA in up-regulating p-JAK 2 and p-STAT 3 protein expression
      (P<0.05). CONCLUSION: Both EA and MA stimulation can reduce the obese rats' body
      weight, and Lee's index, which may be closely associated with their effects in
      down-regulating serum leptin and in enhancing hepatocellular p-JAK 2 and p-STAT 3
      protein expression.

PMID- 25845213
TI  - [Effects of scalp-acupuncture on astrocyte apoptosis in hippocampal CA 1 region
      in rats with vascular dementia].
AB  - OBJECTIVE: To observe the effect of scalp-acupuncture intervention on the
      expression of Bcl-2 of astrocytes in the hippocampus in vascular dementia (VD)
      rats, so as to reveal its underlying mechanism in improving VD. METHODS: A total
      of 40 male SD rats were randomly divided into normal control, sham-operation, VD
      model, and scalp-acupuncture groups (n=10 in each group). The VD model was
      established by using modified Pulsinelli 4-vessel-occlusion method. Scalp
      acupuncture was applied to bilateral "Daozang Shangjiao" and bilateral "Jiyi",
      and "Siwei" acupoints according to FANG's scalp-acupuncture therapy for 30 min,
      once daily for 10 days. The rat's learning-memory ability was detected by Morris
      water maze tests, and the expression of apoptosis related proteins Bcl-2 of
      astrocytes in the hippocampus was detected by immunofluorescence double labeling
      technique and Western blot, respectively. RESULTS: Morris water maze tests showed
      that the average escape latency of place navigation test and the duration of the
      first platform-site crossover (space probing test) were significantly increased
      in the model group compared with the normal control group (P<0.01), and the
      number of platform-site crossovers in 2 min was markedly decreased in the model
      group (P<0.01). The increased average escape latency and the increased duration
      of first platform-site crossover were markedly shortened in the scalp-acupuncture
      group in comparison with the model group (P<0.01), and the number of the platform
      crossovers in 2 min was significantly increased in the scalp-acupuncture group
      (P<0.01). The expression of Bcl-2 protein and the number of GFAP/Bcl-2-labeled
      cells of hippocampal CA 1 region in the model group were remarkably decreased
      compared with the normal control group (P<0.01). After scalp-acupuncture
      intervention, the decreased Bcl-2 protein expression level and the number of
      double-labeled GFAP/Bcl-2 cells were significantly up-regulated in the scalp
      acupuncture group compared with the model group (P<0.01). No significant
      differences were found between the normal control and sham-operation groups in
      the escape latency, duration of the first platform-site crossover, number of
      platform crossovers in 2 min, number of GFAP/Bcl-2 double labeled cells and the
      expression level of hippocampal Bcl-2 protein (P>0.05). CONCLUSION: Scalp
      acupuncture can effectively regulate the expression of apoptosis related proteins
      Bcl-2 of astrocytes in the CA 1 region of hippocampus in rats with VD, which may
      contribute to its effect in the improvement of VD.

PMID- 25845214
TI  - [Effect of electroacupuncture intervention on expression of testicular P 450
      scc/17 beta-HSD3 in rats with partial androgen deficiency].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) intervention on
      expression of cytochrome P 450 side chain cleavage (P 450 scc) and 17 beta
      hydroxysteroid dehydrogenase 3 (17 beta-HSD3) in the testis in partial androgen
      deficiency of aging male (PADAM) rats so as to reveal its mechanism underlying
      improving PADAM. METHODS: Thirty male SD rats were randomly and equally divided
      into control, model, and EA groups. The PADAM model was established by
      intraperitoneal injection of cyclophosphamide (20 mg . kg(-1) . d(-1)), once
      daily for 5 days. EA (20-30 Hz, 1-3 mA) was applied to bilateral "Shenshu" (BL
      23) and "Guanyuan" (CV 4) for 15 min, once daily for 8 weeks. Serum total
      testosterone (TT) and free testosterone (FT) levels were measured using enzyme
      linked immunosorbent assay (ELISA). The expression levels of P 450 scc/17 beta
      HSD3 proteins and mRNA in the testis tissue were assayed by immunohistochemistry,
      Western bolt (WB) and RT-polymerase chain reaction (RT-PCR), separately. RESULTS:
      Compared with the control group, both serum TT, FT levels and expression levels
      of P450 scc/17 beta-HSD3 proteins and mRNA in the testis tissue in the model
      group were significantly down-regulated (P<0.01). After EA intervention, compared
      with the model group, the cyclophosphamide-induced decrease of serum TT, FT
      levels and the expression levels of P 450 scc/17 beta-HSD3 proteins and mRNA in
      the testis was reversed in the EA group (P<0.01). CONCLUSION: EA intervention is
      effective in up-regulating serum TT and FT, testicular P 450 scc and 17 beta-HSD3
      proteins and mRNA levels in PADAM rats, which may be one of its mechanisms
      underlying improvement of PADAM.

PMID- 25845215
TI  - [Effects of Zhuang-medical thread moxibustion combined with needle-pricking on
      vascular oxidative stress injury in the rat].
AB  - OBJECTIVE: To observe the effect of Zhuang-medical thread moxibustion combined
      with needle-pricking on vascular oxidative stress injury in oxidative stress
      injury rats. METHODS: Eighty Wistar rats were randomly allocated to normal
      control, sham operation (sham), model, and combined treatment groups (n=20 in
      each group). The oxidative stress injury model was established by ligation of the
      left sciatic nerve to induce chronic constriction injury (CCI) pain stress
      stimulation. Zhuang-medical thread moxibustion was applied to bilateral "Zusanli"
      (ST 36), once a day for 3 weeks. Needle-pricking was applied to left
      "Yanglingquan" (GB 34) and left "Huantiao" (GB 30), once a day for 3 weeks except
      Sundays. Plasma 6-keto-PGF 1alpha, thromboxane B 2 (TXB 2), NO and ET contents
      were assayed by radioimmunoassay. COX-2 immunoactivity of the femoral artery was
      determined by immunohistochemistry, and pathological changes of the femoral
      artery were detected by H. E. staining. RESULTS: Compared with the control group,
      the levels of plasma 6-keto-PGF 1alpha and NO in the model group were
      significantly reduced (P<0.05), while those of plasma TXB 2 and ET and COX-2
      expression in the femoral artery were obviously increased in the model group
      (P<0.01). After moxibustion plus needle-pricking treatment, CCI-induced decrease
      of plasma 6-keto-PGF 1alpha and NO contents, and increase of plasma TXB 2 and ET
      and COX-2 expression levels were obviously reversed (P<0.05, P<0.01). The tubal
      wall of the femoral artery in rats of the model group got thicker, while that of
      the combined treatment group was relatively thinner, suggesting an inhibition of
      vascular intimal hyperplasia after the treatment. CONCLUSION: Zhuang-medical
      thread moxibustion combined with needle-pricking of ST 36, GB 34 and GB 30 can
      reduce the expression of femoral artery COX-2 and regulate the balance of both
      plasma PGI 2/TXA 2 and plasma NO/ET in CCI-induced oxidative stress rats, which
      may contribute to its effect in suppressing oxidative stress-induced vascular
      intimal hyperplasia.

PMID- 25845216
TI  - [Effects of electroacupuncture on learning-memory ability and expression of
      hippocampal vascular endothelial growth factor (VEGF), VEGF receptor 1 and 2
      genes in vascular cognitive impairment rats].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) of "Dazhui" (GV 14),
      "Baihui" (GV 20), etc. on learning-memory ability and expression of vascular
      endothelial growth factor (VEGF) mRNA, VEGF receptor 1 (VEGFR-1/Flt-1) mRNA, and
      VEGFR-2 (Flk-1) mRNA in the hippocampus in vascular cognitive impairment (VCI)
      rats so as to reveal its mechanism underlying improvement of VCI. METHODS: A
      total of 60 Wistar rats were randomly divided into sham operation, VCI model, EA
      and medication groups (n=12 in each group). The VCI model was established by
      occlusion of the bilateral vertebral arteries and bilateral cervical arteries. EA
      (2 Hz/20 Hz) was applied to "Baihui" (GV 20), "Dazhui" (GV 14), "Shuigou" (GV 26)
      and "Shenting" (GV 24) for 20 min, once daily for 20 days. Rats of the medication
      group were treated by intragastric perfusion of Aniracetam capsules (0.0625
      g/kg),once daily for 20 days. The rats' learning-memory ability was detected by
      step-down test. The expression levels of VEGF mRNA, Flt-1 mRNA and Flk-1 mRNA in
      the hippocampus were detected by RT-PCR, and the neurological deficit scores were
      assessed by Zea Longa (0-4 scaling) method. RESULTS: Compared with the sham
      operation group, rats of the model group showed a significant increase in
      reaction time and error number and decrease of escape latency (reduction of
      learning-memory ability), and increase in neurological deficit score, and in
      expression levels of hippocampal VEGF mRNA, Flt-1 mRNA and Flk-1 mRNA (all
      P<0.01). After EA treatment, in comparison with the model group, the learning
      memory ability and hippocampal VEGF mRNA, Flt-1 mRNA and Flk-1 mRNA were
      apparently increased, neurological deficit score were markedly decreased in the
      EA group (all P<0.01). The effects of EA treatment was obviously superior to
      those of medication in raising learning-memory ability and up-regulating
      hippocampal VEGF mRNA and Flt-1 mRNA expression levels, and in reducing
      neurological deficit score (all P<0.05). CONCLUSION: EA intervention can
      apparently up-regulate hippocampal VEGF mRNA, Flt-1 mRNA and Flk-1 mRNA
      expression in VCI rats, which may contribute to its effect in improving learning
      memory ability, possibly by promoting neovasculization.

PMID- 25845217
TI  - [Effect of electroacupuncture stimulation of "Baihui" (GV 20) and " Yongquan" (KI
      1) on expression of hippocampal amyloid-beta and low density lipoprotein receptor
      related protein-1 in APP/PS 1 transgenic mice].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) treatment on the
      level of hippocampal amyloid-beta peptide (Abeta) and its key transport receptor
      low density lipoprotein receptor-related protein-1 (LRP 1) in APP/PS 1 transgenic
      mice so as to explore its mechanism underlying improvement of Alzheimer's disease
      (AD). METHODS: Twenty-four male APP/PS 1 transgenic mice were equally and
      randomly divided into model group and EA treatment group, and 12 C 57 BL/6 mice
      were used as the normal control group. EA (1 Hz/50 Hz, 0.3 mA) was applied to
      "Baihui" (GV 20) and "Yongquan" (KI 1) for 15 min, once every other day for 6
      weeks. The learning-memory ability was detected by using Morris water maze
      testing, left hippocampal Abeta 1-40 and Abeta 1-42 contents were assayed by
      ELISA, and right hippocampal LRP 1 expression was detected using Western blot
      (WB). RESULTS: Results of Morris water maze test showed no significant
      differences among the three groups in the escape latency, the times of the
      platform-site crossovers, the time spent in the target platform quadrant
      (P>0.05). Compared with the model group, the moderately increased escape latency
      had a decreasing tendency in the EA treatment group. ELISA assaying showed that
      hippocampal Abeta 1-42, Abeta 1-40, and ratio of Abeta 1-42/Abeta 1-40 of the
      model group were significantly higher than those of the normal control group
      (P<0.01). After EA intervention, the increased Abeta 1-42 , Abeta 1-40, and ratio
      of Abeta 1-42/Abeta 1-40 were remarkably down-regulated in the EA treatment group
      (P<0.01). WB detection displayed that the right hippocampal LRP 1 expression
      level of the model group was markedly lower than that of the normal control group
      (P<0.05). After EA treatment, LRP 1 expression level was moderately up-regulated
      but without significant difference between the model and EA treatment groups
      (P>0.05). CONCLUSION: EA intervention can lower the level of hippocampal Abeta in
      APP/PS 1 transgenic mice, but its effects on Abeta transport receptor LRP 1
      expression and learning-memory ability need being confirmed further.

PMID- 25845218
TI  - [Effect of electroacupuncture of "Xiaohai" (SI 8) and "Xiajuxu" (ST 39) on serum
      TNF-alpha and duodenal high mobility group protein B 1 levels in duodenal ulcer
      rats].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) stimulation of
      "Xiaohai" (SI 8) and "Xiajuxu" (ST 39) on serum TNF-alpha and duodenal high
      mobility group protein B 1 (HMGB 1) levels in rats with duodenal ulcer (DU), so
      as to analyze its underlying mechanism in improving DU. METHODS: Forty SD rats
      were randomly divided into normal control, model, Xiaohai (SI 8) and Xiajuxu (ST
      39) groups (n=10 in each group). The DU model was established by intramuscular
      injection of 10% Cysteamine hydrochloride (300 mg/kg), followed by taking water
      containing 1% Cysteamine hydrochloride for 48 h. EA (10 Hz/50 Hz, 1-3 mA) was
      applied to bilateral SI 8 and ST 39 for 30 min, once a day for 10 days. The DU
      score (0-5 score) was evaluated according to Moraes' method. Serum TNF-alpha
      content was determined by ELISA and duodenal HMGB 1 expression was measured by
      immunohistochemistry. RESULTS: Compared to the normal control group, the DU
      score, serum TNF-alpha content, and duodenal HMGB 1 expression level of the model
      group were significantly higher (P<0.01). Following EA intervention, the
      increased DU score, serum TNF-alpha content, and duodenal HMGB 1 expression level
      were considerably down-regulated in the two EA groups in comparison with the
      model group (P<0.01, P<0.05) except HMGB 1 in the SI 8 group (P>0.05), and the
      effect of EA of "Xiajuxu" (ST 39), the lower-He point, was remarkably superior to
      that of "Xiaohai" (SI 8) in reducing DU score and TNF-alpha content (P<0.01).
      CONCLUSION: EA stimulation of SI 8 and ST 39 can improve duodenal ulceration in
      DU rats, which may be related to its effect in down-regulating serum TNF-alpha
      and duodenal HMGB 1 expression. The therapeutic effect of ST 39 is markedly
      better than SI 8 in relieving duodenal ulceration.

PMID- 25845219
TI  - [The impact of different duration of EA-pretreatment on expression of MMP-9 and
      VEGF in blood-brain barrier in rats with cerebral ischemia-reperfusion injury].
AB  - OBJECTIVE: To observe the impact of preconditioning of EA stimulation of "Baihui"
      (GV 20) and "Shuigou" (GV 26) in different duration on expression of matrix
      metalloproteinase (MMP)-9 and vascular endothelial growth factor (VEGF) in blood
      brain barrier (BBB) tissues in rats with cerebral ischemia-reperfusion injury
      (CI/RI). METHODS: Sixty-four male SD rats were randomly allocated to sham
      operation (sham), model, EA-pretreatment 7 days (pre-t-7 d) and EA-pre-t-15 d
      groups (16 rats/group, 8 rats for immunohistochemistry and 8 for RT-PCR). The
      CI/RI model was established by occlusion of the middle cerebral artery for 90 min
      and reperfusion. EA (2 Hz/15 Hz, 1 mA) was applied to GV 20 and GV 26 for 30 min,
      once daily for 7 days and 15 days respectively before modeling.
      Immunohistochemical staining and fluorescence quantitative RT-PCR were employed
      to detect the expression of MMP-9 protein, MMP-9 mRNA and VEGF mRNA in the BBB
      tissues (choroid plexus). RESULTS: Compared with the sham group, the number of
      MMP-9 immuno-reaction positive cells, and the expression of MMP-9 mRNA and VEGF
      mRNA in the model group were significantly increased (P<0.001), while compared
      with the model group, the number of MMP-9 positive cells, and expression levels
      of MMP-9 mRNA and VEGF mRNA in the EA-pre-t-7 d and EA-pre-t-15 d groups were
      significantly reduced (P<0.01), and the effects of EA-pre-t-15 d were markedly
      superior to those of EA-pre-t-7 d (P<0.01, P<0.05). CONCLUSION: EA-pretreatment
      of GV 20 and GV 26 can effectively restrain CI/RI-induced increase of expression
      of MMP-9 protein, MMP-9 mRNA and VEGF mRNA in blood-brain barrier in CI/RI rats,
      which may contribute to its protective effect of ischemic cerebral tissue. Longer
      EA-pretreatment is relatively better.

PMID- 25845220
TI  - [Effect of electroacupuncture stimulation of "Neiguan" (PC 6) on expression of
      alpha- and beta-subunit proteins of voltage-gated sodium channels in rats with
      myocardial ischemia].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) stimulation of
      "Neiguan" (PC 6) on expression of sodium (Nav) channel alpha-subunit 1.5 and Nav
      beta-subunits beta 1-beta 4 (the known myocardial sodium channel proteins) in
      acute myocardial ischemia (AMI) rats so as to explore its mechanisms underlying
      protection of ischemic myocardium. METHODS: Sixty SD male rats were randomly
      divided into normal control, AMI model, Neiguan (PC 6), Lieque (LU 7) and non
      acupoint groups. The AMI model was established by intravenous injection of
      Isoprenaline (85 mg/kg) once daily for 2 days. Myocardial Nav 1.5 and Nav beta 1,
      beta 2, beta 3, beta 4 protein expression levels were detected by Western blot.
      RESULTS: In comparison with the control group, myocardial Nav 1.5, beta 1, beta
      2, beta 3 and beta 4 protein expression levels were significantly down-regulated
      in the AMI model group (P<0.01). After EA stimulation, compared with the model
      group, the expression levels of Nav 1.5, Nav beta 1, beta 2, beta 3 and beta 4
      protein expression levels were significantly up-regulated in the Neiguang (PC 6)
      and Lieque (LU 7) groups (P<0.01) rather than in the non-acupoint group (P>0.05).
      There was no statistical significance between the Neiguan (PC 6) and Lieque (LU
      7) groups in beta 4 protein expression level (P>0.05). CONCLUSION: EA stimulation
      of both PC 6 and LU 7 can significantly reverse AMI-induced down-regulation of
      myocardial Nav 1.5, beta 1, beta 2, beta 3 and beta 4 protein expression levels
      in AMI rats, which might contribute to its function in improving AMI by reducing
      calcium overload.

PMID- 25845221
TI  - [The effect of acupuncture stimulation of Ashi-point on hepatocyte growth factor
      expression in the soft tissue in acute contusion rats].
AB  - OBJECTIVE: To observe the effect of acupuncture stimulation of Ashi-point on
      hepatocyte growth factor (HGF) protein expression in gastrocnemius muscle (GM) in
      rats with traumatic injury of GM, so as to reveal its mechanism underlying
      improvement of traumatic injury of skeletal muscle. METHODS: A total of 80 SD
      rats were randomly divided into normal control (n = 8), model, acupuncture
      control, and acupuncture treatment groups, and the latter 3 groups were further
      allocated to 0 h, 24 h and 48 h subgroups (n = 8 in each subgroup). The acute
      soft tissue contusion model was established by using 500 g-counterweight free
      falling hitting at the GM of the right leg (height 30 cm). The Ashi-point was
      punctured with a piece of filiform needle by penetrating the site beside the
      injured GM, and stimulated for about 5 seconds. For acupuncture control group,
      acupuncture was performed in the same Ashi-point in normal rats. Pathological
      changes of the focal GM were observed by H. E. staining and HGF protein
      expression of GM was detected by Western blot. RESULTS: H.E. staining showed that
      different degrees of injury of GM tissue including broken muscle fibers with
      cellular swelling, inflammatory cell infiltration, muscle fibrinolysis, atrophy,
      degeneration and necrosis, etc., were found at each time-point after modeling,
      while in the acupuncture treatment group, the severity of muscle injury was
      relatively milder particularly at the time-points of 24 h and 48 h. Compared with
      the normal control group, HGF protein expression levels of GM at the 3 time
      points in the model group, and at 48 h in the acupuncture control group were
      markedly increased (P<0.05, P<0.01); while in comparison with the model group,
      HGF protein expression levels were remarkably down-regulated at 24 h and 48 h
      after acupuncture treatment (P<0.01, P<0.05). CONCLUSION: Acupuncture stimulation
      of Ashi-point can significantly down-regulate HGF protein expression in the GM in
      soft tissue contusion rats, which may contribute to its effects in relieving
      contusion injury of skeletal muscle.

PMID- 25845222
TI  - [Acupoint injection of kakkonein for early- or mid-stage Parkinson's disease: a
      multicenter randomized controlled clinical trial].
AB  - OBJECTIVE: To investigate short- and long-term benefits and safety of acupoint
      injection of kakkonein for early- or mid-stage Parkinson's disease (PD). METHODS:
      A total of 135 patients with early- or mid-stage PD were enlisted and 116 cases
      completed the observation, including 40 cases in the acupoint-injection group, 37
      cases in the acupuncture group and 39 cases in the medication group. Patients of
      the acupoint-injection group were treated by injection of kakkonein (2 mL) into
      bilateral Fengchi (GB 20), once very other day for 8 weeks. For acupuncture
      intervention, bilateral GB 20 acupoints were punctured with filiform needles,
      once every other day for 8 weeks. Patients of the medication group were treated
      by oral administration of compound levodopa (125 mg/time, twice a day) for 8
      weeks. The disease severity was assessed by using Unified Parkinson's Disease
      Rating Scale (UPDRS, version 3. 0) before and after treatment, and one month
      after the treatment. RESULTS: After the treatment, scores of psychosis, behavior
      and emotion, daily life activity and motor function were all significantly
      decreased in the three groups in comparison with pre-treatment in each group
      (P<0.05), suggesting an improvement of the PD patients' conditions. The
      therapeutic effect of acupoint-injection and acupuncture groups was markedly
      superior to that of the medication group (P<0.05). One-month's follow-up showed
      that the scores of behavior-emotion and daily life activity were obviously lower
      in the acupoint-injection group than in the acupuncture and medication groups
      (P<0.05). No significant differences were found between the acupuncture and
      medication groups in down-regulating scores of behavior-emotion, daily life
      activity and motor function (P>0.05). CONCLUSION: Acupoint injection of kakkonein
      can improve patients' behavior, emotion, and daily life activity in early- or mid
      stage PD patients and has both short- and longer-term benefits.

PMID- 25845223
TI  - [Clinical trials for treatment of primary hyperlipidemia by using acupuncture in
      combination with Lipitor].
AB  - OBJECTIVE: To observe the clinical effect of acupuncture therapy combined with
      Lipitor in the treatment of primary hyperlipidemia (spleen deficiency and food
      stagnation type). METHODS: Sixty primary hyperlipidemia patients (spleen
      deficiency and food stagnation type) were equally randomized into medication
      group and acupuncture plus medication group. Patients of both groups were treated
      by oral administration of Lipitor (20 mg/tablet, one tablet per day) for 6 weeks.
      Manual acupuncture stimulation was applied to Baihui (GV 20), Zhongwan (CV 12),
      and bilateral Zusanli (ST 36), Sanyinjiao (SP 6), Yin-lingquan (SP 9) and
      Fenglong (ST 40) for 40 min, twice daily for 6 weeks except the weekends. Serum
      total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol
      (HDL-C), low density lipoprotein-cholesterol (LDL-C) were detected by using a
      full-automatic biochemistry analyzer before and after the treatment. The
      therapeutic effect was assessed according to the standards described in "Guide
      Principles for Clinical Researches of New Chinese Herbal Drugs". RESULTS: After
      the treatment, the levels of serum TC, TG of the two groups were significantly
      decreased in comparison with pre-treatment in the same one group (P<0.05), and
      the therapeutic effect of the acupuncture+medication group was significantly
      superior to that of simple medication group in lowering serum TC, TG and LDL-C
      levels and heightening HDL-C levels (P<0.05). Of the two 30 cases in the
      medication and acupuncture+medication groups, 2 (6.7%) and 7 (23.3%) were
      basically controlled in their blood-lipid levels, 10 (33.3%) and 15 (50.0%) had a
      marked improvement, 10 (33.3%) and 6 (20.0%) were improved, and 8 (26.7%) and 2
      (6.7%) were invalid, with the effective rates being 73.3% and 93.3%,
      respectively. CONCLUSION: Acupuncture combined with administration of Lipitor is
      effective in improving primary hyperlipidemia in patients, which is superior to
      administration of simple Lipitor.

PMID- 25845224
TI  - [Comparison of therapeutic effects between acupoint-injection and intramuscular
      injection of Bacillus Calmette-Guerin polysaccharide nucleic acid for bronchial
      asthma].
AB  - OBJECTIVE: To observe the curative effect of acupoint-injection and intramuscular
      injection of Bacillus Calmette-Guerin (BCG) Polysaccharide Nucleic Acid for
      bronchial asthma. METHODS: Sixty patients with bronchial asthma were equally
      randomized into acupoint-injection group and intramuscular-injection group. For
      patients of the acupoint-injection group, 2 mL of BCG was injected into bilateral
      Feishu (BL 13, 1 mL for one side) once per day in the first 15 days, and once
      every other day in the rest 2.5 months except weekends. Intramuscular-injection
      was conducted at the lateral sites of the left or right buttock, 2 mL/time for
      each site, and the injection frequency was the same to that of the acupoint
      injection. The therapeutic effect was assessed according to the standards of
      Guide Principles for Clinical Research of New Chinese Herbal Drugs (2002) and
      Asthma Group of Breathing Diseases of China Medical Association (2008). Changes
      of FEV 1 (forced expiratory volume in the first second)/FVC (forced vital
      capacity) and PEF% (peak expiratory flow) were detected using a pulmonary
      function detector. Serum IgA, IgM, IgG and IgE contents were assayed by using an
      autonomic biochemical analyzer. RESULTS: After 3 months' treatment, the scores of
      patients' symptoms and signs and serum IgE and IgG levels were significantly
      decreased in both muscular-injection and acupoint-injection groups (P<0.01),
      while asthma controlled test (ACT) scores FEV 1/FVC% and PEF% values were
      considerably increased in both groups compared to pre-treatment in the same one
      group (P<0.01). The effects of acupoint-injection were markedly superior to those
      of the intramuscular-injection in reducing clinical symptom-sign score, and serum
      IgE content, and in up-regulating ACT score, FEV 1/FVC% and PEF% levels (P<0.05,
      P<0.01). There were no significant differences in serum IgG, IgA and IgM levels
      between the two groups 3 months following the treatment (P>0.05). CONCLUSION:
      Acupoint-injection of BCG polysaccharide nucleic acid can effectively improve
      bronchial asthma patients' clinical symptoms and sings and pulmonary function,
      which may be closely associated with its function in down-regulating serum IgE
      and IgG levels.

PMID- 25845225
TI  - [Body acupuncture combined with auricular acupressure for menstrual headache: a
      randomized controlled clinical trial].
AB  - OBJECTIVE: To observe the therapeutic effect of body acupuncture combined with
      auricular acupressure for treatment of menstrual headache of hyperactivity of
      "liver fire". METHODS: A total of 85 menstrual headache patients with
      hyperactivity of "liver-fire" were randomly divided into control group (n = 42)
      and treatment group (n = 43). Patients of the control group were treated by oral
      administration of Flunarizine Hydrochloride Capsules (Sibelium, 5 mg/time, twice
      daily) for 5 days beginning at the headache attack in the first menstrual cycle,
      and for two weeks (except weekends) in the second and third menstrual cycles.
      Patients of the treatment group were treated by manual acupuncture stimulation of
      body acupoints Baihui (GV 20), Fengchi (GB 20), Sanyinjiao (SP 6), Taichong (LR
      3), Xiaxi (GB 43), Taiyang (EX-HN 5), Hanyan (GB 4), Xuanlu (GB 5) and Shuaigu
      (GB 8) beginning from the headache attack, and otopoint-pellet pressure of
      otopoints unilateral Endocrine, Ovaries, Shenmen, Cortex, Liver, Spleen and
      Kidney (beginning 5 days before menstrual onset) and bilateral Shenmen, Nie,
      Liver, Gallbladder, Subcortex and Jiaogan during headache attack. Clinical
      symptom scores were assessed according to the "Guiding Principles for Clinical
      Research on New Chinese Herbal Drugs" issued by the Chinese Ministry of Health.
      RESULTS: After the treatment, of the 42 and 43 cases in the control and treatment
      groups, 9 (21.43%) and 20 (46.51%) were cured, 12 (28.57%) and 14 (32.56%) had a
      marked improvement, 13 (30.95%) and 7 (16.28%) were effective, 8 (19.05%) and 2
      (4.65%) invalid, with the effective rates being 80.95% and 95.35% , respectively.
      The curative effect of the treatment group was significantly better than that of
      the control group (P<0.05). The symptom score and VAS score after the treatment
      and 3 months post-treatment in the treatment group were significantly lower than
      those of the control group (P<0.01). The headache scores and VAS scores were
      significantly reduced following the treatment and 3 months after the treatment in
      both control and treatment groups (P<0.01). After the treatment for 2-3
      therapeutic courses, the headache attack duration during menstruation was
      markedly and gradually shortened in both groups (P<0.01), and therapeutic effect
      of the treatment group was significantly better than that of the control group
      (P<0.01). CONCLUSION: Body acupuncture combined with auricular acupressure
      treatment can effectively relieve menstrual headache in menstrual women with
      hyperactivity of "liver fire".

PMID- 25845226
TI  - [Design and establishment of modern literature database about acupuncture Deqi].
AB  - A search on acupuncture Deqi was conducted using four Chinese-language biomedical
      databases (CNKI, Wan-Fang, VIP and CBM) and PubMed database and using keywords
      "Deqi" or "needle sensation" "needling feeling" "needle feel" "obtaining qi",
      etc. Then, a "Modern Literature Database for Acupuncture Deqi" was established by
      employing Microsoft SQL Server 2005 Express Edition, introducing the contents,
      data types, information structure and logic constraint of the system table
      fields. From this Database, detailed inquiries about general information of
      clinical trials, acupuncturists' experience, ancient medical works, comprehensive
      literature, etc. can be obtained. The present databank lays a foundation for
      subsequent evaluation of literature quality about Deqi and data mining of
      undetected Deqi knowledge.

PMID- 25845227
TI  - [Mast cell-derived exosome participates in acupoint-stimulation initiated local
      network activities].
AB  - The exosome, released from mast cells, T cells, B cells and many other types of
      cells, is the common form of vesicle transportation between cells and
      participates in the exchange of information between cells, and may be also
      involved in acupuncture induced clinical effects. In the present paper, the
      authors reviewed recent development of researches on this field from 1)
      acupuncture stimulation induces changes of number and function of mast cells in
      the local acupoint area, probably being the key factor for initiating acupuncture
      effect; 2) acupuncture stimulation induces release of neurotransmitters,
      hormones, cytokines, Ca2+, etc., in the local acupoint region, possibly being
      closely associated with the production of clinical effects; 3) acupuncture
      stimulation results in excitation of sensory afferent nerve fibers, triggering
      neuro-regulation; 4) exosomes derived from mast cells contain multiple
      neurotransmitters, hormones, cytokines, etc. to activate immune cells and sensory
      afferent fibers, inducing immuno-regulation and neuro-regulation; and 5)
      acupuncture stimulation induced release of Ca2+, ATP, etc. may potentiate release
      and transportation of exosomes. However, current researches are lack of
      excavation of network connection and transformation from basic research to
      clinical application. The authors hold that the exosome, released from mast cells
      by needling acupoints, acts as a messenger in network connection of nerve-mast
      cell-signal molecule in the body and may be one of the key factors of therapeutic
      effects.

PMID- 25845228
TI  - [Diverse functions of fibulin-5 in tumors].
AB  - Altered interactions between the extracellular matrix and cells play an important
      part in tumorigenesis and metastasis. As a member of matricellular glycoprotein,
      fibulin-5 is expressed in elastin-rich tissues and organizes the matrix
      structures by interacting with many extracellular proteins. Fibulin-5 expression
      is closely associated with normal embryonic development and organogenesis. Mice
      deficient for the fibulin-5 gene exhibit systemic elastic fiber defects with
      manifestation of loose skin, emphysematous lung and tortuous vessels.
      Additionally, fibulin-5 null mice exhibited increased angiogenesis after wound
      healing or PVA sponge implantation and matrigel implantation experiments show
      fibulin-5 inhibited vessel formation, suggesting fibulin-5 functions as an
      angiogenesis inhibitor. Fibulin-5 also plays critical roles in proliferation,
      migration and invasion of certain tumors, and the effect of fibulin-5 on
      tumorigenesis appears to be largely context-dependent. This effect might involve
      the inhibiting action of fibulin-5 on angiogenesis. This review focuses on recent
      advances in our understanding of the roles of fibulin-5 in tumorigenesis: both
      tumor promoting and suppressing activity of fibulin-5 are reviewed, and the
      emerging evidences of its promising potential as therapeutic options and/or
      targets in the treatment of cancer also highlighted.

PMID- 25845229
TI  - [Fluorescence in situ hybridization with DNA probes derived from individual
      chromosomes and chromosome regions].
AB  - A significant part of the eukaryotic genomes consists of repetitive DNA, which
      can form large clusters or distributed along euchromatic chromosome regions.
      Repeats located in chromosomal regions make a problem in analysis and
      identification of the chromosomal material with fluorescence in situ
      hybridization (FISH). In most cases, the identification of chromosome regions
      using FISH requires detection of the signal produced with unique sequences. The
      feasibility, advantages and disadvantages of traditional methods of suppression
      of repetitive DNA hybridization, methods of repeats-free probe construction and
      methods of chromosome-specific DNA sequences visualization using image processing
      of multicolor FISH results are considered in the paper. The efficiency of
      different techniques for DNA probe generation, different FISH protocols, and
      image processing of obtained microscopic images depends on the genomic size and
      structure of analyzing species. This problem was discussed and different
      approaches were considered for the analysis of the species with very large
      genome, rare species and species which specimens are too small in size to obtain
      the amount of genomic and Cot-1 DNA required for suppression of repetitive DNA
      hybridization.

PMID- 25845230
TI  - [G-quadruplex ligands: mechanisms of anticancer action and target binding].
AB  - Since the discovery of potential therapeutic value of quadruplex secondary
      nucleic acids structures, many compounds that stabilize these targets were found.
      Such progress became possible due to understanding of the structural features of
      G-quadruplexes. Quadruplex ligands selectively suppress the growth of tumor cells
      by indirect inhibition of the telomerase activity and/or attenuation of
      oncogenes' overexpression. Therapeutic effect demonstrated in vivo supports the
      prospect of such compounds for the development of the targeted anticancer drugs.
      This review reveals the significance of G-quadruplexes as therapeutic targets and
      focuses on biochemical properties of the low molecular weight quadruplex ligands.

PMID- 25845231
TI  - [The gene expression of the protein SLAWD, mediating the toxic effect of
      destruxin A on Spodoptera litura larvae, in procaryotic cells: purification and
      characterization].
AB  - Spodoptera litura is one of the most destructive phytophagous pest infesting
      cotton, vegetable, oilseed and ber crops around the world. Dextruxin A (DA), is a
      one of a kind microbial insecticide, which has potent toxins with bioactivity
      against S. litura larvae. An abnormal wing disc (AWD) protein was identified as a
      DA toxic effect protein in S. litura SL-1 cells. To better understand the role of
      the AWD gene of S. litura (SLAWD) it was purified and characterized. The entire
      coding region of the SLAWD gene was cloned into a pET-32a(+) expression vector
      and transformed into competent Escherichia coli BL21 (DE3) cells. SDS-PAGE and
      western blotting analysis and western blotting showed that the best induction
      conditions were 1 mmol mL(-1) isopropyl-beta-D-thiogalactopyranoside (IPTG) for 6
      h at 37 degrees C; the molecular weight of the fusion protein was 35.0 kDa. The
      production of polyclonal antibodies and an enzyme-linked immunosorbent assay
      (ELISA) showed that the titer of antiserum was 1:25,600; western blotting
      analysis showed that the recombinant SLAWD was recognized by the anti-SLAWD
      polyclonal antibody. AWD is a key protein involved in wing development in
      insects. These tools will assist in the further characterization of SLAWD and
      studies on the mechanism of action of destruxin A.

PMID- 25845232
TI  - [Differential gene expression in incompatible interaction between Lilium regale
      Wilson and Fusarium oxysporum f. sp. lilii revealed by combined SSH and
      microarray analysis].
AB  - Fusarium wilt, caused by a soilborne pathogen Fusarium oxysporum f. sp. lilii, is
      the major disease of lily (Lilium L.). In order to isolate the genes
      differentially expressed in a resistant reaction to F. oxysporum in L. regale
      Wilson, a cDNA library was constructed with L. regale root during F. oxysporum
      infection using the suppression subtractive hybridization (SSH), and a total of
      585 unique expressed sequence tags (ESTs) were obtained. Furthermore, the gene
      expression profiles in the incompatible interaction between L. regale and F.
      oxysporum were revealed by oligonucleotide microarray analysis of 585 unique ESTs
      comparison to the compatible interaction between a susceptible Lilium Oriental
      Hybrid 'Siberia' and F. oxysporum. The result of expression profile analysis
      indicated that the genes encoding pathogenesis-related proteins (PRs),
      antioxidative stress enzymes, secondary metabolism enzymes, transcription
      factors, signal transduction proteins as well as a large number of unknown genes
      were involved in early defense response of L. regale to F. oxysporum infection.
      Moreover, the following quantitative reverse transcription PCR (QRT-PCR) analysis
      confirmed reliability of the oligonucleotide microarray data. In the present
      study, isolation of differentially expressed genes in L. regale during response
      to F. oxysporum helped to uncover the molecular mechanism associated with the
      resistance of L. regale against F. oxysporum.

PMID- 25845233
TI  - [Evaluation of reference genes for quantitative real-time PCR normalization in
      cotton bollworm, Helicoverna armigera].
AB  - Reverse-transcription quantitative real-time PCR (RT-qPCR), a sensitive technique
      is being extensively employed in quantification of gene expression. However this
      requires normalization with suitable reference gene (RG) which is crucial in
      minimizing inter sample variations. Information regarding suitable RG is scarce
      in general and more so in insects, including the cotton bollworm, Helicoverpa
      armigera, an economically important pest. In management of this pest RNA
      interference (RNAi), is perceived as a potential tool, which is achieved by
      double-stranded RNA (dsRNA) delivery. These studies demand accurate
      quantification of gene silencing. In this study we assessed the suitability of
      five RGs viz. beta-actin (ACTB), 18S rRNA (18S), glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH), beta-tubulin (TUB) and elongation fator-1-alfa (EF1-alpha)
      for gene expression studies in dsRNA treatment and across different developmental
      stages of H. armigera and ranked using geNorm, NormFinder and BestKeeper software
      programs. Data analysis revealed that best ranked RGs were varied in dsRNA
      treatment and in developmental stages. Under dsRNA treatment, 18S and GAPDH were
      more stable whereas, TUB and GAPDH were more stable across developmental stages.
      We also demonstrate that inappropriate selection of RG led to erroneous
      estimation of the target gene, chymotrypsin, expression. These results facilitate
      accurate quantification of gene expression in H. armigera.

PMID- 25845234
TI  - [Association of the nicotine and cigarette smoke toxicants metabolic (CHRNA3/5,
      CYP2A6, NQO1) and DNA repair genes (XRCC1, XRCC3, XPC, XPA) with chronic
      obstructive pulmonary disease].
AB  - The contribution of the polymorphic markers of the CHRNA5/A3, CYP2A6, NQO1, XPC,
      XRCC1, XRCC3, XPD, XPA genes to chronic obstructive pulmonary disease has been
      assessed. For this purpose, analysis of the gene polymorphisms in case/control
      groups in Tatar population has been performed. The CHRNA5 (rs16969968) (P =
      0.0001, OR = 2.24), CHRNA3 (rs1051730) (P = 0.0001, OR = 2.72) were associated
      with significantly high risk of chronic obstructive pulmonary disease in
      recessive model. The disease risk was higher in homozygous carriers of normal
      allele of CYP2A6 (del) (P = 0.00001, OR = 2.77). Analysis showed an association
      of the NQO1 (rs1131341), XRCC1 (rs25487), XRCC3 (rs861539), XPC (rs2228001) and
      XPA (rs1800975) (P = 0.000001, OR = 2.67; P = 0.00001, OR = 0.51; P = 0.0003, OR
      = 1.76; P = 0.0004, OR = 0.54 and P = 0.007, OR = 0.74) in additive model with
      chronic obstructive pulmonary disease. We found a significant gene-by-environment
      interaction of smoking status and XPA (rs1800975) (Pinteract = 0.002);
      rs16969968, rs1051730 of CHRNA3/5 genes were significantly associated with
      chronic obstructive pulmonary disease only in smokers. The relationship between
      the CYP2A6(CYP2A6*4) and smoking pack-years was found (P = 0.0019). The TT
      genotype of XRCC3 (rs861539) were associated with decreased of lung function
      parameters: vital capacity % (P = 0.0487), forced vital capacity (%) (P = 0.0032)
      and forced expiratory volume in 1 s (%) (P = 0.02). The relationship between the
      XPA (rs1800975) and forced expiratory volume in 1 s (%) (P = 0.0028) was found.

PMID- 25845235
TI  - [Replicative association analysis of genetic markers of cognitive traits with
      Alzheimer's disease in a Russian population].
AB  - Replicative association analysis of Alzheimer's disease (AD) with 15 genetic
      markers associated with cognitive traits in genome-wide association studies was
      performed. In a Russian populations associations of rs2616984 in CSMD1 gene with
      AD (OR = 1.50, 95% CI = 1.07-2.09, p-value = 0.018) and putative associations
      with the disease of rs3131296 in NOTCH4 gene (OR = 1.53, 95% CI = 0.98-2.39, p
      value = 0.06) and rs2229741 of NRIP1 gene (OR = 1.35, CI = 0.99-1.85, p-value =
      0.061) were revealed. Combinations of epistatic interacting genes (CSMD1 and
      NRIP1; NOTCH4, CSMD1 and NRIP1; TLR4, CSMD1 and NRIP1) were found, as well as
      their genotypes combinations significantly associated with AD and characterized
      by highest predictive values. Probable molecular mechanisms implicated in the
      relation of genes under study to AD pathogenesis are discussed. Bioinformatic
      analysis of biological processes, molecular functions and protein-protein
      interactions of BA genes demonstrated that genes under study may play modulating
      and modifying role by participation in various regulatory and signal pathways
      involved in a disease development.

PMID- 25845236
TI  - [Effect of tumor necrosis factor-related apoptosis-inducing ligand on developing
      human oligodendrocytes in culture].
AB  - Accumulating evidence suggests that proinflammatory cytokines play an important
      role in white matter injury in preterm infants, a condition in which
      oligodendrocyte (OL) progenitor cells are preferentially injured. We investigated
      the role of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)
      and its death (TRAIL-R1, TRAIL-R2) and decoy (TRAIL-R3, TRAIL-R4) receptors in
      periventricular white matter injury (PWMI). We hypothesized that the maturation
      dependent vulnerability of OLs to TRAIL is due to differential TRAIL receptor
      expression. We previously investigated TRAIL/TRAIL receptor expression levels in
      rat OLs in vivo in the context of PWMI. We found that during different
      developmental stages, human OLs differentially express TRAIL receptors; there is
      a progressive loss of sensitivity to TRAIL as OLs proceed through the maturation
      process. Our results show that both TRAIL-R1 and -R2 are highly expressed on
      human OL progenitors and pre-OLs, while TRAIL-R3 and TRAIL-R4 are mainly
      expressed on immature and mature human OLs. Our results suggest that TRAIL-R1 and
      TRAIL-R2 might mediate the death signal in human OL precursor cells and pre-OLs.

PMID- 25845237
TI  - [Auto-inducible expression system based on the SigB-dependent ohrB promoter in
      Bacillus subtilis].
AB  - The reliable production of heterologous proteins is important in the field of
      industrial biotechnology. This can be achieved by applying auto-inducible gene
      expression systems. The development of a Bacillus subtilis expression plasmid
      harboring SigB-dependent ohrB promoter was reported. The expression system was
      subjected to high cell density cultivation to produce xylanase as a stable model
      protein. The recombinant strain was cultured in a synthetic medium containing
      glucose as the carbon source. The exponential fed-batch feeding strategy was
      applied to prevent substrate inhibition. A sharp increase of xylanase activity
      (about 6-fold) at the end of the fermentation was observed as a result of sigma
      factor B (SigB) protein activation, supporting auto-inducibility of the
      expression system. For the control strain a specific induction of the xylanase
      activity was not observed. The recombinant strain was capable to offer a 5-fold
      increase in xylanase activity in comparison with the control strain. In addition,
      the constructed system displayed catabolite repression resistance ability. This
      SigB-dependent expression system can be considered as a biotechnology tool and an
      alternative to eliminate the cost of conventional inducers, e.g. isopropyl-beta
      galactopyranoside.

PMID- 25845238
TI  - [The role of some individual amino acid substitutions in penicillin-binding
      protein (PBP2) of Neisseria gonorrhoeae in the emergence of resistance to
      ceftriaxone].
AB  - The goal of the study was to identify amino acid replacements in the structure of
      penicillin-binding protein PBP2, which may influence on the development of
      resistance N. gonorhoeae to the III cephalosporins generation. The gene penA of
      50 strains of N. gonorrhoeae was sequenced: 20 strains with high sensitivity to
      ceftriaxone (MIC, Minimum Inhibitory Concentration, = 0.002 mg/L) and 30 strains
      with decreased sensitivity to ceftriaxone (MIC = 0.03-0.25 mg/L). The difference
      of MIC sensitivity between these strains was 30-250 times. Then nucleotide
      sequence was transformed into the amino acid sequence of PBP2 protein. Mutations
      in the gene penA and amino acid replacements in the protein PBP2 were found in 16
      of 20 strains (80%) with high sensitivity to ceftriaxone and in all strains with
      decreased sensitivity to ceftriaxone. Amino acid replacements in the PBP2 protein
      were compared with amino acid replacements in groups, which characterize the PBP2
      structure in accordance with the international classification Ito M. The amino
      acid replacement of PBP2 at positions 346, 505, 511, 517, 543, 567, 575, 576 are
      associated with V group by Ito M and have features of resistance of N.
      gonorrhoeae to ceftriaxone authentically (OR = 3.9 +/- 2.5; chi2 = 4.9; p <
      0.05). It was shown that the replacement of glycine to serine at position 543 of
      PBP2 in the analyzed strains induced the multiple increase of resistance to
      ceftriaxone. These data may be significant as showing strong influence of amino
      acid replacements at positions 346, 505, 511, 517, 567, 575 and, in particular,
      543 for development of resistance N. gonorrhoeae strains to ceftriaxone.

PMID- 25845239
TI  - [The effect of central administration of the neurotrophic factors BDNF and GDNF
      on the functional activity and expression of the serotonin 5-HT2A receptors in
      mice genetically predisposed to depressive-like behavior].
AB  - Brain serotonin (5-HT) system plays an important role in the control of normal
      and pathological behavior. 5-HT2A receptors are widely implicated in the
      regulation both normal functions and psychopathologies, especially schizophrenia
      and depression. Here, we investigated implication of 5-HT2A receptor in
      mechanisms of neurotrophic factors BDNF and GDNF action. We found that the acute
      intracerebroventricular injection of BDNF produced considerable increase in 5
      HT2A receptor functional activity in ASC mice. Moreover, BDNF injection led to
      the increasing of 5-HT2A receptor gene expression in the hippocampus and its
      decrease in the frontal cortex without any effects in the midbrain. On the
      contrary, GDNF injection failed to alter 5-HT2A receptor functional activity, but
      increased the 5-HT2A receptor gene expression in the frontal cortex without any
      effects in the hippocampus and midbrain. Thus, an effect of the central
      administration of the neurotrophic factors BDNF and GDNF on the 5-HT2A receptor
      functional activity and gene expression was shown. The results indicate the
      implication of 5-HT2A receptor in the mechanisms of BDNF and GDNF action.

PMID- 25845240
TI  - [Role of reactive oxygen species in the bactericidal action of quinolones-
      inhibitors of DNA gyrase].
AB  - Quinolone antibiotics inhibit DNA gyrase, but the induced degradation of
      chromosomal DNA is determined by a complex process of joint action quinolones and
      hydroxyl radical OH'. To quantify the level of stress responses and their time
      dependence in bacterial cells the induced specific lux-biosensors--the bacterium
      Escherichia coli, containing hybrid plasmids pColD'::lux; pSoxS'::lux;
      pKatG'::lux were used in this study. It is shown that quinolones (nalidixic acid,
      norfloxacin) induce SOS-response and oxidative stress with the formation of
      superoxide anion O2(-) in E. coli cells. The main parameters of SOS-response and
      oxidative stress, which depend on the quinolone concentration, are determined.
      Formation of superoxide anion O2(-) occurs almost simultaneously with the SOS
      response. The mutant strain of E. coli sodA sodB, which do not contain active
      forms of superoxide dismutases SodA and SodB, is characterized by an increased
      resistance to quinolones as compared to the wild type cells. At high
      concentrations of quinolones (nalidixic acid-->20 MUg/mL; norfloxacin-->500
      ng/mL) their bactericidal effect is partially caused by conversion of the
      superoxide anion to hydrogen peroxide H2O2, conducted by superoxide dismutases
      SodA and SodB, which is followed by the Fenton reaction and the formation of
      toxic hydroxyl radical OH'. At low concentrations of quinolones (nalidixic acid-
      <20 MUg/mL; norfloxacin--<500 ng/mL), the role of active oxygen species in the
      antimicrobial effect is practically nonexistent.

PMID- 25845241
TI  - [Transcripts of satellite DNA in blood plasma: probable markers of tumor growth].
AB  - A recent study of human normal and tumor tissues revealed a high transcriptional
      activity of pericentromeric satellite DNA repeats (they produce half of all
      transcripts in tumor cells that is many times higher than in normal ones). It was
      found also that the two subtypes of satellite DNA (HSATII and GSATII) are
      transcribed reciprocally, i.e. there is a sharp prevalence of HSATII
      transcription in tumors, while GSATII transcription prevails in the corresponding
      normal tissues. As different RNAs are present in blood plasma, and some of them
      serve as effectivetumor markers, we attempted for the first time to evaluate
      satellite HSATII and GSATII RNAs in the blood plasma of healthy donors and cancer
      patients. The RT-PCR protocol designed for this purpose allowed us to detect
      transcripts of both HSATII and GSATII repeats. As it has been shown, HSATII
      transcripts are more abundant than GSATII ones in plasma of healthy donors and
      vice versa in plasma of cancer patients; these ratios being diametrically opposed
      to those that exist within the cells. Some suggestions concerning origins of
      circulating satellite RNAs and their probable role as tumor markers are
      discussed.

PMID- 25845242
TI  - [Spatial organization of house-keeping genes in interphase nuclei].
AB  - Spatial organization of the eukaryotic genome is tightly connected to its
      functioning. In particular, the interaction of gene promoters with remote
      enhancer elements in active chromatin hubs, as well as the recruitment of genes
      to the common transcription factories plays an important role in regulation of
      gene transcription. Most of works related to the analysis of spatial interaction
      of genome regulatory elements relies on models of tissue-specific genes.
      Meanwhile, it remains unclear to which extent the spatial organization of
      chromosomes is guided by house-keeping genes that are transcribed in most of cell
      types and outnumber the transcribed tissue-specific genes. To address this
      question, we used the 4C technique to characterize genome-wide the spatial
      contacts of the chicken house-keeping genes CARHSP1 and TRAP1 situated on
      chromosome 14. The promoters of these genes had an increased frequency of
      interaction with chromosome regions enriched in CpG islands and binding motifs
      for the ubiquitous transcription factor Sp1, both of which mark promoters of
      house-keeping genes, and overall with transcriptionally active regions. By
      contrast, the analysis of interaction of a gene poor region of chromosome 14
      revealed no such preferences. The evidence for the interaction of house-keeping
      gene promoters were also obtained in independent cytological experiments aimed at
      visualization of non-methylated CpG islands in individual nuclei of human cells,
      which showed clustering of CpG islands in the nuclear space. Altogether, the
      results of our work suggest that the interaction of house-keeping genes
      constitutes an important factor that determines the spatial organization of
      interphase chromosomes.

PMID- 25845243
TI  - [NMR screening of potential inhibitors of Citrobacter freundii methionine].
AB  - Methionine gamma-lyase [EC 4.4.1.11] participates in a methionine catabolism at a
      number of bacteria and protozoa eukaryotes, including pathogenic microorganisms.
      Lack of this enzyme at mammals allows consider it as a perspective target for
      rational antibacterial drug design. Currently in medical practice there are no
      the preparations based on an inhibition of methionine gamma-lyase activity. We
      present results of the search of potential inhibitors of the enzyme using the NMR
      screening techniques based on identification of compounds, which able to bind
      specifically to their biological target. Study included a stage of in silico
      virtual screening of the library of commercially available compounds and
      subsequent experimental selection of the leading compounds, capable to interact
      with enzyme. Identification of binding was carried out by means of saturation
      transfer difference (STD) spectroscopy and WaterLOGSY technique. At the final
      stage the experimental assessment of inhibiting ability of the selected compounds
      in the reaction of gamma-elimination of L-methionine catalyzed by methionine
      gamma-lyase was carried out. Binding constants of two leading compounds were
      determined using the WaterLOGSY method. The research expands structural group of
      potential inhibitors of methionine gamma-lyase and allows approach to the design
      of the inhibitors with higher efficacy.

PMID- 25845244
TI  - [Molecular-and-genetic diversity of cyanophages of the family Myoviridae in Lake
      Hovsgol (Mongolia)].
AB  - Cyanophages of the family Myoviridae were studied in Lake Hovsgol based on the
      analysis of g20 gene fragments. The analysis revealed the diversity of g20
      cyanomyovirus sequences in Lake Hovsgol. It was found a great similarity of genes
      from the Lake Hovsgol and Lake Baikal. Distribution of closely related virus
      strains in these water bodies is attributed to close geographical location,
      direct water connection and similar hydrochemical parameters of the lakes.

PMID- 25845245
TI  - [Depressive symptoms and cognitive dysfunctions in patients with chronic
      hepatitis B].
AB  - INTRODUCTION: Pronounced symptoms of depression and disorders of cognitive
      functions can be observed in patients with chronic hepatitis B. OBJECTIVE: The
      objective of the study was evaluation of the severity of symptoms and predictive
      factors for depression and the existence of cognitive disorders in patients with
      chronic hepatitis B. METHODS: A total of 150 respondents were included in this
      prospective study (50 patients with chronic hepatitis B, 50 patients with other
      chronic liver diseases and 50 healthy persons). The patients with chronic
      hepatitis B were homogeneous by age compared to healthy subjects (p = 0.566) and
      patients with other chronic liver diseases (p = 0.528). Assessment of intensity
      of depression was determined by the Hamilton Depression Rating Scale (HAMD). A
      Mini Mental State Examination (MMSE) test was used to investigate the presence of
      cognitive disorders. RESULTS: Significantly expressed depression was observed in
      patients with chronic hepatitis B compared with healthy persons as well as the
      occurrence of cognitive dysfunction (p = 0.00), while in comparison with the
      patients with chronic nonviral liver diseases, depression was statistically
      significantly less markedly expressed (p = 0.003). Depression and cognitive
      dysfunction were more noticeable in patients with chronic hepatitis B in the
      stage of liver cirrhosis in relation to the early stage of the disease.
      Multivariate analysis of variables related to the sociodemographic
      characteristics showed that the most significant positive predictor of depression
      was more expressed in older age (over 50 years) (B = 0.276; SE = 0.092; p =
      0.004). CONCLUSION: Patients with chronic hepatitis B have a higher intensity of
      depression compared to healthy people, which is intensified with the progression
      of the disease. The highest expression of depression is expected in the elderly.
      Patients with chronic hepatitis B have a lower intensity of depression and fewer
      disorders of cognitive functions than patients with other chronic liver diseases.

PMID- 25845246
TI  - Changes in soft tissue profile using functional appliances in the treatment of
      skeletal class II malocclusion.
AB  - INTRODUCTION: The effects of orthodontic treatment are considered to be
      successful if the facial harmony is achieved, while the structures of soft tissue
      profile are in harmony with skeletal structures of neurocranium and
      viscerocranium. In patients with skeletal distal bite caused by mandibular
      retrognathism, facial esthetics is disturbed often, in terms of pronounced
      convexity of the profile and change in the position and relationship of the lips.
      OBJECTIVE: The aim of this study was to determine the extent of soft tissue
      profile changes in patients with skeletal Class II malocclusion treated with
      three different orthodontic appliances: Frankel functional regulator type I (FR
      I), Balters' Bionator type I and Hotz appliance. METHODS: The study included 60
      patients diagnosed with skeletal Class II malocclusion caused by mandibular
      retrognathism, in the period of early mixed dentition. Each subgroup of 20
      patients was treated with a variety of orthodontic appliances. On the lateral
      cephalogram, before and after treatment, the following parameters were analyzed:T
      angle, H angle, the height of the upper lip, the position of the upper and lower
      lip in relation to the esthetic line.Within the statistical analysis the mean,
      maximum, minimum, standard deviation, coefficient of variation, two-factor
      analysis of variance with repeated measures and the factor analysis of variance
      were calculated using ANOVA, Bonferroni test and Student's t-test. RESULTS: A
      significant decrease of angles T and H was noticed in the application of FR-I,
      from 21.60 degrees  to 17.15 degrees , and from 16.45 degrees  to 13.40 degrees 
      (p < 0.001). FR-I decreased the height of the upper lip from 26.15 mm to 25.85
      mm, while Hotz appliance and Balters' Bionator type I increased the height of the
      upper lip, thereby deteriorating esthetics of the patient. CONCLUSION: All used
      orthodontic appliances lead to changes in soft tissue profile in terms of
      improving facial esthetics, with the most distinctive changes in the application
      of Frankel's functional regulator type I, which is the most successful appliance
      for achieving the overall facial harmony of the patient.

PMID- 25845247
TI  - Application of digital radiography for measuring in clinical dental practice.
AB  - INTRODUCTION: The recent literature data points out a rising application of
      digital radiography--radiovisiography (RVG)--in dental clinical practice.
      OBJECTIVE: The aim of this study was to apply and compare RVG with the
      conventional radiographic technique (CRDG) in terms of accuracy in linear
      measurement in dentistry. METHODS: Measurements were done on the mandibular dogs
      teeth considering incisors crown width and height of the surrounding alveolar
      bone using RVG and CRDG.The control technique (CONT) involved values obtained by
      direct gauging in dogs mouth. Each measuring was done by two examiners. RESULTS:
      Considering the incisors' crown width, there were no significant statistical
      difference in measurement using CRDG, RVG and CONT technique (p > 0.01).
      Concerning the alveolar height gauging there were no significant difference in
      recorded values between the two radiographic techniques (p > 0.01). The high
      level of inter-examiner agreement was observed for scoring in all techniques
      (CRDG, RVG and CONT). CONCLUSION: Although RVG did not expose more accuracy
      comparing to CRDG, having opulent tool service the first technique contributed
      more comfortable work during measuring procedures in this study.

PMID- 25845248
TI  - [The role of cardiac pacing therapy in the management of carotid sinus syndrome].
AB  - INTRODUCTION: Carotid sinus syndrome is characterized by a hypersensitive carotid
      sinus and syncope. Although we have clear guidelines for the diagnosis and
      treatment of carotid sinus syndrome, the efficacy of pacing therapy with this
      indication has not been the subject of many studies. OBJECTIVE: This study aimed
      to assess the efficacy and safety of pacing therapy in the treatment of patients
      with carotid sinus syndrome and to determine the factors contributing to symp-
      toms recurrence after pacemaker implantation. METHODS: This study was
      retrospective and included 32 patients in whom a pacemaker was implanted due to
      carotid sinus syn- drome at the Pacemaker Center, Clinical Center of Serbia, be-
      tween April 2005 and April 2012. Carotid sinus massage and head-up tilt test
      (HUTT) were performed to select patients with cardioinhibitory and mixed type
      carotid sinus syndrome, who were enrolled to the study. RESULTS: The mean age of
      patients was 65.6 +/- 11.5 years and 20 (62.5%) were men. The mean follow-up
      period was 4.3 +/- 1.9 years. HUTT was performed in 3 (9.4%) patients. Twenty
      seven (84.4%) patients presented with cardioinhibitory and 5 (15.6%) with mixed
      type of carotid sinus syndrome. After pacemaker implantation, 22 (68.7%) patients
      had no further symptoms, 8 (25.0%) had syncope and 2 (6.3%) presyncope.The mixed
      type of the disease (HR 3.1; 95% CI 1.4-5.1; p = 0.021) and implanta- tion of
      pacemaker in WI mode (HR 1.8; 95% CI 1.1-3.2; p = 0.034) were independent
      predictors of symptoms recurrence. There were 3 (9.4%) perioperative surgical
      complications. CONCLUSION: Pacemaker therapy is an effective and safe treat- ment
      for patients with carotid sinus syndrome. As predictors of symptoms persistence
      after pacemaker implantation in our population, we identified the implantation of
      pacemaker in WI mode and the mixed type of carotid sinus syndrome.

PMID- 25845249
TI  - Osteoporosis--a risk factor for cardiovascular diseases: a follow-up study.
AB  - INTRODUCTION: Cardiovascular (CV) diseases and bone fractures due to osteoporosis
      are the leading causes of death in the elderly. OBJECTIVE: The aim of this study
      was to demonstrate a correlation between the overall risk for CV events, and low
      bone density in postmenopausal women, and its impact on the incidence of serious
      CV events. METHODS: Our prospective study involved 300 postmenopausal women. All
      the examinees were divided into three groups based on their measured bone
      density: Group I--84 examinees with osteoporosis; Group II--115 examinees with
      osteopenia; and Group III--101 examinees with normal bone density. In all
      examinees the overall ten-year risk for a fatal CV event was calculated using the
      SCORE system tables. RESULTS: After a 36-month follow-up, CV events occurred in
      19 (6.3%) examinees. Significant differences in the incidence of CV events were
      demonstrated between the patients with osteoporosis, osteopenia, and normal bone
      density (chi2 = 28.7; p < 0.001), as well as between those with a high and low CV
      risk (chi2 = 22.6; p < 0.001). Multivariate logistic regression analysis showed
      that smoking (OR: 2.23; 95% CI: 1.02 to 6.19; p = 0.035), and increase of overall
      CV score (OR: 1.36; 95% CI: 1.17 to 1.58; p < 0.001) are associated with
      increased CV event risk, while the increase of T score value is associated with
      decreased risk of CV event (OR: 0.42; 95% CI: 0.25 to 0.73; p = 0.002).
      CONCLUSION: Measurement of bone density with a standard assessment of the total
      CV risk could be useful for selecting women who need intensive prevention and
      treatment of atherosclerosis.

PMID- 25845250
TI  - Boceprevir in genotype 1 chronic hepatitis C: first experiences in Serbia.
AB  - INTRODUCTION: The triple therapy which consists of one of the protease inhibitor
      plus pegylated interferon and ribavirin (P/R) is the standard of care for the
      treatment of chronic hepatitis C virus (HCV) genotype 1 (G1) infection both in
      treatment-naive and experienced patients. OBJECTIVE: The aim of this study was to
      analyze the efficacy and tolerability of this regime in hospital practice in
      Serbia. METHODS: From July 2012 to October 2012, 20 previously treated patients
      with advanced fibrosis and HCV G1 infection were included in the triple antiviral
      regimen in six referral centers in Serbia. All patients were treated with
      response guide therapy (RGT) regime according to the boceprevir treatment
      protocol. During the 4-week lead-in period all patients received peginterferon
      plus ribavirin. After the lead-in pe- riod boceprevir was added in the dosage of
      800 mg three times a day orally.The subsequent treatment varied according to
      virologic response and fibrosis. During the therapy HCV RNA level was measured at
      week 4, 8, 12, 24 of the treatment for the assessment of virologic response
      profile. All patients who completed therapy were assessed at the end of the
      treatment and at the end of an additional 24-week treatment-free period for a
      sustained virologic response (SVR). RESULTS: The total of 20 patients with
      advanced fibrosis was treated. Among patients with an undetectable HCV RNA level
      at week 8 the rate of SVR was 100%. No patient with decrease in the HCV RNA level
      < 1 log 10 IU/ml at treatment week 4 achieved SVR. The overall rate of SVR was
      55%. The safety profile of the treatment regimen was good. Anemia was reported in
      25% of patients. There was no life-threatening treatment adverse event.
      CONCLUSION: Boceprevir in combination with P/R achieved fairly good SVR rates in
      patients that were"most difficult to treat"who failed on dual therapy and was
      effective among patients with cirrhosis.

PMID- 25845251
TI  - Significance of immunohistochemical expression of p16INK4a in the differentiation
      of inflammatory and preneoplastic cervical lesions.
AB  - INTRODUCTION: Most studies point at the main role of humanpapilloma virus (HPV)
      in the development of dysplasia and cervical cancer. Due to the low specificity
      and sensitivity of morphological diagnostic methods it is necessary to find an
      adequate marker which would be introduced in the screening program for cervical
      cancer. Most research suggests that p16INK4a is a specific and sensitive marker.
      OBJECTIVE: The aim of this research was to determine the presence of p16INK4a
      expression in inflammatory and preneoplastic lesions of the cervix. METHODS: The
      study was performed on 73 samples of cervical biopsy. In 34 patients a
      preneoplastic change (dysplasia) in the stratified squamous cervix epithelium was
      found, and in 39 a non-specific inflammatory process was disclosed. In all
      samples, immunohistochemical analysis using antibodies to p16INK4a was performed.
      RESULTS: The expression of p16INK4a was verified in 67.65% of cases in dysplastic
      cervical lesions and 38.5% of the inflammatory lesions. A statistically
      significant difference was determined in the presence and grade of expression
      between dysplastic and inflammatory lesions of the cervix (chi2 = 24.16; p <
      0.001). The expression was more frequent and had a higher grade in dysplastic
      lesions with high grade and showed a statistically significant difference
      compared to the expression in low-grade dysplasia (chi2 = 21.48; p < 0.001).
      CONCLUSION: The analysis of the presence of p16INK4a can differentiate non
      neoplastic from preneoplastic changes in the cervix. It is recommended to use
      immunocytochemical and immunohistochemical analysis using p16INK4a in
      interpreting borderline lesions of the cervix.

PMID- 25845252
TI  - Estimation of angiotensin-converting enzyme inhibitors protein binding degree
      using chromatographic hydrophobicity data.
AB  - INTRODUCTION: Angiotensin-converting enzyme (ACE) inhibitors represent a
      significant group of drugs primarily used in the treatment of hypertension and
      congestive heart failure. OBJECTIVE: Selected ACE inhibitors (enalapril,
      quinapril, fosinopril, lisinopril, cilazapril) were studied in order to establish
      a fast and easy estimation method of their plasma protein binding degree based on
      their lipophilicity data. METHODS: Chromatographic hydrophobicity data (parameter
      C0) were obtained on cellulose layers under conditions of normal-phase thin-layer
      chromatography (NPTLC), using different binary solvent systems. The ACE
      inhibitors lipophilicity descriptors (logP) values were calculated using the
      software package Virtual Computational Chemistry Laboratory.The ACE inhibitors
      plasma protein binding data were collected from relevant literature. RESULTS: ACE
      inhibitors protein binding data varied from negligible (lisinopril) to 99%
      (fosinopril). The calculated lipophilicity descriptors, logP(KOWWIN) values
      ranged from -0.94 (lisinopril) to 6.61 (fosinopril). Good correlations were
      established between plasma protein binding values and calculated logP(KOWWIN)
      values (R2 = 0.8026) as well as chromatographic hydrophobicity data, C0
      parameters (R2 = 0.7662). Even though good correlation coefficients (R2) were
      obtained in both relations, unacceptable probability value with p > 0.05 was
      found in relation between protein binding data and calculated logP(KOWWIN)
      values. Subsequently, taking into consideration the request for probability value
      lower than 0.05, a better relationship was observed between protein binding data
      and chromatographically obtained hydrophobicity parameters C0 values. CONCLUSION:
      Cellulose layers are easily available and cost effective sorbent to assess
      hydrophobicity. Experimentally obtained data on ACE inhibitors hydrophobicity and
      plasma protein binding estimation are important parameters in evaluating
      bioavailability of these drugs.

PMID- 25845253
TI  - [Applying the model of excellence in dental healthcare].
AB  - INTRODUCTION: Models of excellence are considered a practical tool in the field
      of management that should help a variety of organizations, including dental, to
      carry out the measurement of the quality of provided services, and so define
      their position in relation to excellence. The quality of healthcare implies the
      degree within which the system of healthcare and health services increases the
      likelihood of positive treatment outcome. OBJECTIVE: The aim of the present study
      was to define a model of excellence in the field of dental healthcare (DHC) in
      the Republic of Serbia and suggest the model of DHC whose services will have the
      characteristics of outstanding service in the dental practice. METHODS: In this
      study a specially designed questionnaire was used for the assessment of the
      maturity level of applied management regarding quality in healthcare
      organizations of the Republic of Serbia. The questionnaire consists of 13 units
      and a total of 240 questions. RESULTS The results of the study were discussed
      involving four areas: (1) defining the main criteria and sub-criteria, (2) the
      elements of excellence of DHC in the Republic of Serbia, (3) the quality of DHC
      in the Republic of Serbia, and (4) defining the framework of the model of
      excellence for the DHC in the Republic of Serbia. The main criteria which defined
      the framework and implementation model of excellence in the field of DHC in
      Serbia were: leadership, management, human resources, policy and strategy, other
      resources, processes, patients' satisfaction, employee's satisfaction, impact on
      society and business results. The model had two main parts: the possibilities for
      the first five criteria and options for the other four criteria. CONCLUSION:
      Excellence in DHC business as well as the excellence of provided dental services
      are increasingly becoming the norm and good practice, and progressively less the
      exception.

PMID- 25845254
TI  - Primary lymphoma of the brain in a young man whose brother died of hemophagocytic
      lymphohistiocytosis: case report.
AB  - INTRODUCTION: We represent the unique occurrence of primary central nervous
      system lymphoma (PCNSL) in a patient whose brother died of genetically confirmed
      hemophagocytic lymphohistiocytosis (HLH). CASE OUTLINE: We report a case of a 25
      year-old male patient with primary aggressive diffuse large B-cell lymphoma
      affecting the brain and PCNSL. Despite one year of medical treatment outcome was
      lethal. However, our patient had a relatively longer survival compared to median
      survival time for PCNSL. Additionally, he had two older brothers who died at the
      age of about 11 years. One died of fulminate malignancy, shortly after pediatric
      admission, before the diagnosis could be established. The other one died from
      genetically confirmed (perforin mutation/PRF1) HLH. Our patient was heterozygous
      carrier of perforin mutation representing the genetic marker for HLH. Our
      patient's father was the carrier of the same mutation but had no symptoms of any
      disease. CONCLUSION: This case points at the presence of HLH and diffuse large B
      cell PCNSL in brothers. Extensive assessment of patients with probable PCNSL and
      familial HLH is necessary, including genetic analysis for HLH.

PMID- 25845255
TI  - Intracardiac extension of the inferior vena cava leiomyosarcoma with Budd-Chiari
      syndrome presentation: a case report.
AB  - INTRODUCTION: Leiomyosarcomas of the inferior vena cava are rare malignant
      tumors. A limited number of these cases have been described so far. Only few of
      them have intracardiac propagation and surgery is rarely undertaken for their
      treatment. CASE OUTLINE: We present a 52-year-old female patient in whom
      leiomyosarcoma of the inferior vena cava with intracardiac propagation was
      diagnosed. The patient underwent successful surgical treatment with complete
      removal of the tumor and direct suture of the inferior vena cava. No additional
      modalities of therapy were undertaken. CONCLUSION: Surgery, without radiation
      therapy can be a successful option for the treatment of inferior vena cava
      leiomyosarcoma with a good short-term result.

PMID- 25845256
TI  - Surgical treatment of median arcuate ligament syndrome: case report and review of
      literature.
AB  - INTRODUCTION: Median arcuate ligament (MAL) syndrome, also called celiac trunk
      compression syndrome (CACS) or Dunbar syndrome is a rare disorder caused by
      compression of the celiac artery by median arcuate ligament of the diaphragm,
      which leads to mesenteric ischemia and chronic abdominal angina. The typical
      clinical triad of symptoms includes postprandial epigastric pain, weight loss and
      vomiting. The gold standard for MAL syndrome diagnosis is selective angiography,
      while in symptomatic patients with angiographically verified stenosis the optimal
      therapy is surgical treatment. CASE OUTLINE: A 40-year-old male patient was
      presented with epigastric pain, followed by dyspepsia and weight loss. The upper
      endoscopy showed gastric and duodenal distention with prominent folds of gastric
      mucosa and slow peristalsis. Selective angiography showed stenosis (90%) of
      initial segment of the celiac trunk. Adhesiolysis with the transection of the
      median arcuate ligament was performed. Due to repeated symptoms, the patient was
      reoperated on the 10th postoperative day with performed adhesiolysis and
      gastrostomy for gastric nutrition. Two months later, the patient was
      rehospitalized for closure of gastrostomy. At five years follow-up, selective
      angiography showed no stenosis of the initial segment of the celiac artery.
      CONCLUSION: Despite the existing controversy concerning pathophysiological
      mechanism, the clinical presentation and treatment modalities of patients with
      MAL syndrome, it is evident that careful selection and adequate surgical
      treatment may significantly reduce symptoms in these patients.

PMID- 25845257
TI  - [Axial torsion and gangrene of Meckel's diverticulum: case report].
AB  - INTRODUCTION: Meckel's diverticulum (MD) is the most prevalent congenital anomaly
      of small intestine. It develops due to the incomplete obliteration of
      omphalomesenterict duct which normally undergoes obliteration during the seventh
      week of gestation. In the majority of cases MD is asymptomatic but it may cause
      various complications, such as bleeding, intestinal obstruction and inflammation.
      Cases of umbilical sinuses, fistulas and neoplasms related with MD have been
      reported, but extremely rare gangrene due to its axial torsion, especially in
      children, as is the case of our patients. CASE OUTLINE: An 11-year-old boy
      admitted to hospital due to 24 hours epigastric pain, vomiting and malaise. After
      a complete physical examination, and appropriate pre-surgical laboratory and
      radiographic tests, surgical exploration was performed with a midline abdominal
      incision. On 60th cm proximal to the ileocecal valve we found a long and in a
      narrow based ganrenous MD with axial torsion and fibrotic cord extending from the
      tip of MD to the ileal mesentery. Surrounding ileum had normal appearance. A
      demarcation and subsequent resection of MD and the surrounding ileum was
      performed with end-to-end ileal anastomosis. Postoperative recovery was
      successful and the patient was discharged after six days. CONCLUSION: Axial
      torsion of MD is presented with non-specific abdominal symptoms and difficult
      preoperative diagnosis. The choice of diagnosis and therapy is surgical
      exploration and resection of MD.

PMID- 25845258
TI  - Granulomatosis with polyangitis (Wegener's) and central nervous system
      involvement: case report.
AB  - INTRODUCTION: Granulomatosis with polyangitis (Wegener's) is an antineutrophil
      cytoplasmic antibody (PR3-ANCA)-associated vasculitis, which commonly involves
      the upper and lower respiratory tracts and kidneys. Central nervous system
      involvement is reported in less than 11%, and rarely present at onset. CASE
      OUTLINE: We report the case of a 41-year-old male patient with a high disease
      activity, large organ involvement, as well as central nervous system
      manifestations presented at onset.Treatment with intravenous pulse
      methylprednisolone, followed by the pulsed doses of cyclophosphamide was induced.
      After 6 months of cyclophosphamide pulse therapy a remission was achieved. Next,
      azathioprine was used for maintenance during the next 18 months.There were no
      disease flares during 24-month follow-up. CONCLUSION: Granulomatosis with
      polyangitis (Wegener's) with large organ involvement, affecting the central
      nervous system structures require a rapid diagnosis and intensive medication
      treatment in order to prevent or reduce irreversible damage. Our experience
      confirms the findings reported in the literature that the severe forms of the
      disease are associated with increased probability of achieving remission, which
      reflects increased responsiveness of such patients to immunosuppressant therapy.

PMID- 25845259
TI  - Raw milk consumption and health.
AB  - Contrary to the safe practices of milk pasteurization or sterilization, which
      effectively reduce foodborne outbreaks incidence associated with raw milk and
      dairy products use, outbreaks caused by such products continue to occur. Despite
      this fact, a worldwide movement advocating for the rights of raw milk and cheese
      selling and consumption, due to their specific nutritive characteristics, has
      strengthened significantly in recent years. Traditional agricultural
      manufacturers from Serbia still sell products related to thermally unprocessed
      milk, such as cottage cheese and raw cream. In AP Vojvodina during the period of
      1981-2010 a total of 179 foodborne outbreaks were reported, where the
      incriminated cause of the outbreak were milk or diary. In 126 (70.39%) outbreaks,
      totaling 2276 sick individuals and one casualty, it was confirmed that the
      incriminated food was from the group of dairy products. In 48 instances (26.82%),
      bacteriological tests confirmed that milk and dairy products were excluded as the
      outbreak causes, while in another 5 (2.79%) outbreaks, microbiological analysis
      of food failed to confirm any relation to the actual epidemiological instances.
      In some cases, bacteriological testing of incriminated foods was not possible. In
      the cases of outbreaks associated with the consumption of milk and dairy
      products, traditional raw milk products were cited as being used. Consumption of
      unpasteurized milk and cheese represents public health threat. National and
      international rules ensuring use of safe products for human consumption have to
      set rules of trade of thermally processed milk and products on the market.

PMID- 25845260
TI  - [Injuries and vital reactions patterns in hanging].
AB  - Hanging is a form of ligature strangulation in which the force applied to the
      neck is derived from the gravitational drag of one's own body weight. A furrow
      dessication is the most common form of ligature mark on the skin. The furrow is a
      postmortem phenomenon due to ligature pressure and it is more detectable as the
      suspension time becomes longer.Vital reaction is a phenomenon that shows if the
      injury was pre- mortal. Vital signs could be present at the injury site, thus it
      is termed as local, but they could also be remote from the injury site, and then
      they are termed general vital signs. The presence and recognition of any vital
      reaction in each pathoforensic case indicate vitality of certain injury, which is
      sometimes exceptionally useful in solving the case under investigation. Although
      in cases of hanging there is usually no question about the vitality of injury,
      this does not mean that one should not recognize the type of vital reactions and
      location of occurrence of these phenomena in such cases. Most often they can be
      also useful in the reconstruction of the mechanism. This paper presents most
      common vital reactions in hanging, with explanation of their underlying
      mechanisms, and their significance in forensic pathology is pointed out.

PMID- 25845261
TI  - Fifty years of discovery of alpha-fetoprotein as the first tumor marker.
AB  - Alpha-fetoprotein represents the most prominent oncobiomarker, widely used in the
      diagnosis of hepatocellular carcinoma for monitoring of tumor progression,
      presence of metastasis, assessment of cancer prognosis and successful antitumor
      therapeutic measures. Yuri Semenovich Tatarinov is a Russian scientist who first
      published antigen specific for human hepatocellular carcinoma in 1963. To
      commemorate the 50th anniversary of the discovery of alpha-fetoprotein, 9th
      International Scientific-Practical Conference entitled "Achievements of
      fundamental science and translational medicine capabilities in solving actual
      problems of practical public health" was held from May 6-8th, 2013 in Astrakhan,
      Russia.The conference was held in memory of historical scientific work of Yuri
      Semenovich Tatarinov.

PMID- 25845262
TI  - Giovanni Battista Monteggia (1762-1815).
AB  - Giovanni Battista Monteggia was born in Laverne on the 8th of August 1762.
      Monteggia started his education in the School of Surgery at the Hospital Maggiore
      in Milano in 1779.This hospital was called "Big House"and it is one of the oldest
      medical institutions in Italy. He passed exam in surgery in 1781. Monteggia was
      promoted to assistant at surgery in Maggiore hospital in 1790. He was among the
      first who gave a complete clinical description of polio. He described traumatic
      hip dislocation and special forearm fracture which was named after him. Strictly
      speaking, a Monteggia fracture is a fracture of the proximal third of the ulna
      with an anterior dislocation of the radial head. Monteggia became a member of the
      renewed Institute of Science, Literature and Art in Milano in 1813.

PMID- 25845263
TI  - [Contemporary nuclear medicine diagnostics of neuroendocrine tumors].
AB  - The new positron emission tomography (PET/CT) methods for neuroendocrine tumors
      detection are presented and compared with classic, conventional methods.
      Conventional methods use a gamma scintillation camera for patients with
      neuroendocrine tumor imaging, after intravenous injection of one of the following
      radiopharmaceuticals: 1) somatostatin analogues labeled with indium-111 (111In
      pentetreotide) or technetium-99m (99mTc-EDDA/HYNIC-TOC); 2) noradrenaline
      analogue labeled with iodine-131 or -123 (131/123I-MIBG); or 3) 99mTc(V)-DMSA.
      Contemporary methods use PET/CT equipment for patients with neuroendocrine tumor
      imaging, after intravenous injection of pharmaceuticals labeled with positron
      emitters [fluorine-18 (18F), galium-68 (68Ga), or carbon-11 (11C)]: 1) glucose
      analogue (18FDG); 2) somatostatin analogue (68Ga-DOTATOC/68Ga-DOTATATE/68Ga
      DOTANOC); 3) aminoacid precursors of bioamines: [a) dopamine precursor 18F-DOPA
      (6-18F-dihydroxyphenylalanine), b) serotonin precursor 11C-5HTP (11C-5
      hydroxytryptophan)]; or 4) dopamine analogue 18F-DA (6-18F-fluorodopamine).
      Conventional and contemporary (PET/ CT) somatostatin receptor detection showed
      identical high spe- cificity (92%), but conventional had very low sensitivity
      (52%) compared to PET/CT (97%). It means that almost every second neuroendocrine
      tumor detected by contemporary method cannot be discovered using conventional
      (classic) method. In metastatic pheochromocytoma detection contemporary (PET/ CT)
      methods (18F-DOPA and 18F-DA) have higher sensitivity than conventional
      (131I/123I-MIBG). In medullary thyroid carcinoma diagnostics contemporary method
      ([18F-DOPA) is more sensitive than conventional 99mTc(V)-DMSA method, and is
      similar to 18FDG, computed tomography and magnetic resonance. In carcinoid
      detection contemporary method (18F-DOPA) shows similar results with contemporary
      somatostatin receptor detection, while for gastroenteropancreatic neuroendocrine
      tumors it is worse. To conclude, contemporary (PET/CT) methods for somatostatin
      receptor detection (68Ga-DOTATOC/-NOC/-TATE) in neuroendocrine tumors are much
      more sensitive (almost twice) and more accurate than conventional. Therefore the
      classical methods should be urgently replaced by contemporary methods.

PMID- 25845264
TI  - Writing a case report in English.
AB  - A well-written case report is a clear, concise and informative paper, aimed at
      professionals from different fields of medicine, with the clear purpose to
      explain what lesson is to be learnt from the experience. The aim of this paper is
      to suggest useful guidelines for writing a good case report. It briefly reflects
      different "moves"in this piece of academic writing, thus outlining the required
      form, as well as the four principles of good writing: clarity, honesty, reality
      and relevance.

PMID- 25845265
TI  - Physical-Chemical Characterization of Fruit Purees and Relationship with Sensory
      Analysis Carried out by Infants (12 to 24 mo).
AB  - Fruit purees are one of the foods earliest introduced foods in infants' diet
      during the complementary period. The rheological characteristics together with
      the sensory analysis are decisive factors for the acceptance of the food product
      by the infant. The sensory analysis of three commercial fruit purees (mixed
      fruits, pear, and plum) was studied by employing a new objective sensory
      parameter named as SAIR (Sensory Acceptance by Infants Ratio), which is the
      quotient between the percentage of puree consumed (%) by the time (seconds)
      throughout the storage time. In parallel, the rheological characteristics of the
      purees were analyzed in order to obtain a relationship with the SAIR parameter.
      It was proved that the best acceptance of the product (higher SAIR) was observed
      for such purees showing a lower apparent viscosity (lower consistency index, "K")
      and a less pseudoplastic behavior (higher flow behavior index, "n"). These
      results may help to obtain higher acceptance values based on easy obtainable and
      objective parameters. 

PMID- 25845266
TI  - Stimulus-dependent augmented gamma oscillatory activity between the functionally
      connected cortical neurons in the primary visual cortex.
AB  - Neuronal assemblies typically synchronise within the gamma oscillatory band (30
      80 Hz) and are fundamental to information processing. Despite numerous
      investigations, the exact mechanisms and origins of gamma oscillations are yet to
      be known. Here, through multiunit recordings in the primary visual cortex of
      cats, we show that the strength of gamma power (20-40 and 60-80 Hz) is
      significantly stronger between the functionally connected units than between the
      unconnected units within an assembly. Furthermore, there is increased frequency
      coherence in the gamma band between the connected units than between the
      unconnected units. Finally, the higher gamma rhythms (60-80 Hz) are mostly linked
      to the fast-spiking neurons. These results led us to postulate that gamma
      oscillations are intrinsically generated between the connected units within cell
      assemblies (microcircuits) in relation to the stimulus within an emergent '50-ms
      temporal window of opportunity'.

PMID- 25845267
TI  - Shifts in Buchnera aphidicola density in soybean aphids (Aphis glycines) feeding
      on virus-infected soybean.
AB  - Vertically transmitted bacterial symbionts are common in arthropods. Aphids
      undergo an obligate symbiosis with Buchnera aphidicola, which provides essential
      amino acids to its host and contributes directly to nymph growth and
      reproduction. We previously found that newly adult Aphis glycines feeding on
      soybean infected with the beetle-transmitted Bean pod mottle virus (BPMV) had
      significantly reduced fecundity. We hypothesized that the reduced fecundity was
      attributable to detrimental impacts of the virus on the aphid microbiome, namely
      Buchnera. To test this, mRNA sequencing and quantitative real-time PCR were used
      to assay Buchnera transcript abundance and titre in A. glycines feeding on
      Soybean mosaic virus-infected, BPMV-infected, and healthy soybean for up to 14
      days. Our results indicated that Buchnera density was lower and ultimately
      suppressed in aphids feeding on virus-infected soybean. While the decreased
      Buchnera titre may be associated with reduced aphid fecundity, additional
      mechanisms are probably involved. The present report begins to describe how
      interactions among insects, plants, and plant pathogens influence endosymbiont
      population dynamics. 

PMID- 25845268
TI  - Negative pressure wound therapy technologies for chronic wound care in the home
      setting: A systematic review.
AB  - The use of negative pressure wound therapy (NPWT) is increasing in both the
      inpatient and outpatient settings. We conducted a systematic review on the
      efficacy and safety of NPWT for the treatment of chronic wounds in the home
      setting. We searched MEDLINE, Embase, the Cochrane Central Register of Controlled
      Trials, and the Cumulative Index to Nursing and Allied Health Literature, up to
      June 2014. Two independent reviewers screened search results. Seven studies met
      our criteria for inclusion. Six of the studies compared NPWT devices to other
      wound care methods and one study compared two different NPWT technologies. Data
      were limited by variability in the types of comparator groups, methodological
      limitations, and poor reporting of outcomes. We were unable to draw conclusions
      about the efficacy or safety of NPWT for the treatment of chronic wounds in the
      home setting due to the insufficient evidence. Consensus is needed on the methods
      of conducting and reporting wound care research so that future studies are able
      inform decisions about the use of NPWT in the home environment for chronic
      wounds. 

PMID- 25845269
TI  - Sex differences in the pathways to symptoms of alcohol use disorder: a study of
      opposite-sex twin pairs.
AB  - BACKGROUND: We sought to develop an empirical, broad-based developmental model
      for sex differences in risk for symptoms of alcohol use disorders, here called
      alcohol problems (APs). METHODS: We assessed 18 risk factors in 5 developmental
      tiers in both members of 1,377 opposite-sex dizygotic twin pairs from the
      Virginia population-based twin registry. Analyses were conducted by structural
      modeling, examining within-pair differences. RESULTS: The best-fitting model
      explained 73% of the variance in men and 71% in women for last year AP. Forty
      nine percent of paths differed significantly across sexes. Ten variables had
      appreciably different predictive effects on AP in males versus females. Three
      were stronger in females: familial risk, early-onset anxiety disorders, and
      nicotine dependence. Seven predictors had a stronger total effect in males:
      novelty seeking, conduct disorder, childhood sexual abuse, parental loss,
      neuroticism, low self-esteem, and low marital satisfaction. CONCLUSIONS: In a co
      twin control design, which matches sisters and brothers on genetic and familial
      environmental background, we found numerous sex differences in predictors of last
      year AP. Factors that were more prominent in men and in women were diverse,
      reflecting both internalizing and externalizing psychopathology. The model was
      slightly more successful at predicting AP in men than in women.

PMID- 25845270
TI  - Mode of delivery and childhood fractional exhaled nitric oxide, interrupter
      resistance and asthma: the Generation R study.
AB  - BACKGROUND: Previous studies suggest that caesarean section may influence the
      risk of childhood asthma. We examined the associations of different modes of
      delivery with childhood wheezing patterns, asthma, fractional exhaled nitric
      oxide (FeNO) and airway interrupter resistance (Rint) up to school age. METHODS:
      This study among 6,128 children was embedded in a population-based prospective
      cohort study. Information on mode of delivery was obtained from midwives and
      hospital registries. Wheezing patterns from birth onwards and ever physician
      diagnosed asthma at age 6 yr were assessed by questionnaires. FeNO and Rint were
      measured at age 6 yr. We used multivariate polynomial, logistic and linear
      regression models. RESULTS: Compared with vaginal delivery, caesarean section was
      associated with increased risks of early and persistent wheezing up to school age
      [odds ratios (95% confidence interval): 1.36 (1.06, 1.75) and 1.73 (1.24, 2.40),
      respectively]. The effect sizes of elective and emergency caesarean section with
      wheezing outcomes were similar. Only elective caesarean section was associated
      with a higher FeNO level [sympercent (95% CI): 12.7 (0.6, 24.8)]. We did not
      observe associations of mode of delivery with asthma or Rint. Also, vacuum- or
      forceps-assisted vaginal delivery was not associated with any asthma or related
      outcome. CONCLUSIONS: Both elective and emergency caesarean sections are
      associated with increased risks of early and persistent wheezing up to school
      age. This might be explained by increased airway inflammation reflected by higher
      FeNO levels.

PMID- 25845271
TI  - Reference values of serum IgG and IgM levels in preterm and term newborns.
AB  - AIM: Although, variations of normal immunoglobulin (Ig) levels in different
      gestational age and birth weight groups have been studied so far, data are still
      limited in newborns, especially in preterm infants. The aim of this study was to
      determine serum IgG and IgM levels in newborns in order to generate a reference
      standard for neonatal intensive care unit (NICU) and address the variations in
      preterm babies. METHODS: This study was conducted from June 2012 to June 2013 in
      a level III NICU. A total of 300 newborn infants hospitalized within first 72 h
      were included in the study. The quantification of serum IgG and IgM was performed
      by nephelometric method. RESULTS: Both serum IgG and IgM levels were increased in
      correlation with increased gestational age and birth weight. CONCLUSION: The
      reference values of serum IgG and IgM levels should be further evaluated in
      larger series with the presented data in this article. In addition, preterm
      babies appear to have lower Ig levels thus carry the risk of relevant morbidity.

PMID- 25845272
TI  - Sirenomelia: a review of embryogenic theories and discussion of the differences
      from caudal regression syndrome.
AB  - OBJECTIVE: To discuss the pathological features of sirenomelia in the light of
      our 10 cases and review the current theories. METHODS: We identified 10 patients
      with sirenomelia from our hospital database. All clinical details and the autopsy
      features of 10 cases were noted. RESULTS: Of the 10 children with sirenomelia
      seven had bilateral renal agenesis, three had bladder agenesis and one had a
      renal hypoplasia. Single umbilical artery was found in 60% of children with
      sirenomelia. External genitalia was ambiguous in seven of 10 patients.
      CONCLUSIONS: Even though the etiology of caudal regression syndrome (CRS) and
      sirenomelia remains unknown we tend to believe that sirenomelia and CRS might be
      different entities.

PMID- 25845273
TI  - The role of interleukin-17 in intrahepatic cholestasis of pregnancy.
AB  - OBJECTIVE: Intrahepatic cholestasis of pregnancy (ICP) is the most common
      pregnancy-specific liver disease, is characterized by pruritus, abnormal liver
      function and elevated serum bile acid levels. The main cause of ICP has not yet
      been identified. We aimed to provide a new perspective to the pathogenesis of by
      investigating the possible association of circulating interleukin-17 (IL-17) that
      is a recently discovered proinflammatory cytokine levels with ICP. MATERIALS AND
      METHODS: In this controlled cross-sectional study, maternal venous blood samples
      were obtained from 33 consecutive pregnant women with ICP (15 with mild and 18
      with severe forms of the disease) and 25 healthy women with uncomplicated
      pregnancies (as the control group) and IL-17 levels were compared among the
      groups. RESULTS: Although serum IL-17 levels were significantly higher in the
      severe ICP group than in the control group (p = 0.022), there were no significant
      differences between the mild and severe ICP groups or between the control and
      mild ICP groups. CONCLUSION: Explaining the mechanisms of hepatocyte injury might
      contribute to the existing therapeutic strategies for treating cholestatic
      diseases. Changes in IL-17 levels may shed light on the pathogenesis of ICP.

PMID- 25845274
TI  - Use of intracervical balloons and chorioamnionitis in term premature rupture of
      membranes.
AB  - OBJECTIVE: To determine whether ripening and induction in patients with term
      premature rupture of membranes (PROM) via intracervical balloon placement (ICB)
      increases the risk of chorioamnionitis when compared to women with term PROM
      ripened and induced with other methods. STUDY DESIGN: A retrospective cohort
      study of term singleton gestations undergoing ripening and induction after PROM
      between July 2009 and June 2012 was conducted. Exposure of interest was ICB
      placement. Primary outcome of interest was chorioamnionitis. Statistical analysis
      included bivariate and multivariate techniques. RESULTS: Of 124 term PROM
      patients, 42 were ripened by ICB with or without oxytocin (33.9%) and 82 were
      ripened and induced with oxytocin (66.1%). More women ripened with an ICB were
      nulliparous (n = 35, 83.3% ICB versus n = 44, 53.7% oxytocin, p = 0.001).
      Chorioamnionitis was slightly more common in women ripened with ICB and/or
      oxytocin versus oxytocin alone but difference did not reach statistical
      significance (p = 0.10). The rate of cesarean delivery, intrauterine pressure
      catheter (IUPC) use, and median lengths of membrane rupture and active labor were
      higher in the ICB group. After adjustment, chorioamnionitis was not correlated
      with ICB placement but with nulliparity [AOR 12.5 (1.36, 114.6), p = 0.03] and
      IUPC use [AOR 4.39 (1.04, 18.5), p = 0.04]. CONCLUSION: Nulliparity and IUPC, not
      ICB placement, were associated with chorioamnionitis.

PMID- 25845275
TI  - The role of placental alpha microglobulin-1 amnisure in determining the status of
      the fetal membranes; its association with preterm birth. Traditions ...
      traditions ....
AB  - The integrity of the fetal amnion-chorion is an imperative for the preservation
      of a normal pregnancy in the human. The diagnosis of the status of the fetal
      membranes has traditionally been reduced to either intact or ruptured. In the
      last decades, evidence has accumulated demonstrating that this clinical approach
      may well be an over simplification. Practically, all maternal organs experienced
      physiologic or eventually pathologic changes during the length of the gestational
      period. We propose that the fetal membranes are also significantly impacted by
      those changes. The accurate, specific, simplified and low-cost diagnosis of the
      status of the fetal membranes is of critical importance for the assessment of
      risk to the pregnancy followed by efficient and prompt treatment. The presence of
      placental alpha macroglobulin-1 in the vagina specifically indicates a disruption
      in the integrity of the fetal membranes and may indirectly mean increased risk
      for preterm birth. Further research to properly characterize this marker and its
      importance in the care of pregnant woman at risk for preterm birth is strongly
      recommended. 

PMID- 25845276
TI  - High potassium level during pregnancy is associated with future cardiovascular
      morbidity.
AB  - OBJECTIVE: The present study was aimed to determine whether high potassium level
      during pregnancy is an independent risk factor for future atherosclerotic
      morbidity. PATIENTS AND METHODS: A case-control study was conducted including
      women who delivered between the years 2000-2012 and subsequently developed
      atherosclerotic morbidity after their last delivery (n = 653) and matched
      controls (n = 4101). The mean follow-up duration was 57.7 +/- 36.5 and 78.5 +/-
      42.3 months, respectively. The cases were further divided into: major events
      (severe atherosclerotic morbidity; n = 363), minor events (i.e. cardiovascular
      risk factors; n = 201) and cardiovascular evaluation tests (n = 89). The Cox
      proportional hazards models were used to estimate the adjusted hazard ratios (HR)
      for hospitalizations while controlling for confounders. RESULTS: A Cox
      proportional hazard model, controlling for confounders such as gestational
      hypertension, gestational diabetes mellitus, obesity, maternal age, creatinine
      level and gestational week at index pregnancy showed that K(+ )>= 5.0 mEq/L
      during pregnancy was significantly associated with hospitalizations due to severe
      atherosclerotic morbidity (adjusted HR = 1.55; 95% CI 1.02-2.35; p = 0.039). A
      non-significant trend was also noted with long-term total hospitalizations for
      atherosclerotic (adjusted HR = 1.39; 95% CI 0.99-1.94; p = 0.052). CONCLUSION:
      High potassium level during pregnancy is associated with a significant risk for
      severe atherosclerotic morbidity, as it might be an indication for occult
      metabolic and renal dysfunction.

PMID- 25845277
TI  - Perioperative low-dose ketamine improves postoperative analgesia following
      Cesarean delivery with general anesthesia.
AB  - OBJECTIVE: In this study, the effect of perioperative uses of low dose ketamine
      on post-operative wound pain and analgesic consumption in patients undergoing
      elective Cesarean section was evaluated. METHODS: In randomized, double blind
      clinical trial, 52 women with American Society of Anesthesiologists (ASA) class I
      II identification undergoing elective Cesarean section in general anesthesia were
      enrolled. In the ketamine group (group K), a ketamine bolus of 0.5 mg kg(-1) IV
      was administered at the time of induction of general anesthesia. After induction,
      a ketamine infusion of 0.25 mg kg(-1) h(-1) was started and discontinued at the
      end of surgery. Patients allocated to the control group (group C) were given
      identical volumes of saline. The cumulative dose of morphine consumption after
      surgery was measured as the primary outcome of this study. Secondary outcomes
      were pain control assessed by numeric rating scale (NRS) and need for rescue
      analgesia and incidence of side effects. RESULTS: The mean 24-h morphine
      consumption was lower in group K (p = 0,001). At 15 min postoperatively, NRS
      values were lower in group K than group C (p = 0,001). There was no difference
      among groups regarding the need for supplemental analgesia (rescue diclofenac
      doses) (p > 0.05). CONCLUSIONS: Perioperative uses of low dose ketamine decreased
      post-operative opioid requirements, which was observed long after the normal
      expected duration of ketamine.

PMID- 25845278
TI  - A Pilot Study to Compare Oxidative Status between Organically and Conventionally
      Managed Dairy Cattle During the Transition Period.
AB  - The aim of this study was to assess the redox balance of organically managed
      dairy cattle (OMC; n = 40) during the transition period and to compare this with
      conventionally managed cattle (CMC; n = 22). Serum samples of dairy cows from two
      organic and one conventional farm were taken. Markers of oxidants production
      [reactive oxygen species] and total serum antioxidant capacity were measured in
      four different production stages: (i) far-off dry (2 to 1 months before calving;
      44 samples in CMC and 48 in OMC); (ii) close-up dry (1 month until 3 days before
      calving; 44 CMC; 54 OMC); (iii) fresh (3 days to +1 month after calving; 44 CMC;
      49 OMC); and (iv) peak of lactation (+1 to +3 months; 71 CMC; 78 OMC). Values
      were compared between production stages and against a metabolic baseline status
      (4th-5th month of pregnancy; 40 CMC; 30 OMC). Our results indicated that
      throughout the periparturient period, OMC had lower concentrations of reactive
      oxygen species, but also a lower antioxidant capacity than CMC. Indeed, when the
      two components of the redox balance were assessed together through the Oxidative
      Stress index, the values of this parameter were higher for OMC than for CMC,
      thereby implying a higher risk of oxidative stress. Therefore, further larger
      studies are needed to confirm the current observations, as organically reared
      animals might be exposed to a lack of antioxidants supply. 

PMID- 25845279
TI  - Predicting factors of hypoglycaemia in elderly type 2 diabetes patients:
      Contributions of the GERODIAB study.
AB  - The burden of hypoglycaemia is important, particularly in elderly type 2 diabetes
      (T2D) patients. Unfortunately, however, few studies are available concerning this
      population. GERODIAB is a prospective, multicentre, observational study that aims
      to describe the 5-year morbidity and mortality of 987 T2D patients aged 70 years
      and older. After analyzing the frequency of and factors associated with
      hypoglycaemia in the 6 months prior to study inclusion, it was found that
      hypoglycaemia was associated with retinopathy, lower levels of LDL cholesterol
      and altered mini-Geriatric Depression Scale (GDS) scores.

PMID- 25845280
TI  - Three novel mutations of the ATP2C1 gene in Chinese families with Hailey-Hailey
      disease.

PMID- 25845282
TI  - Absolute reactivity of (N-methyl-3-pyridinium)chlorocarbene.
AB  - (N-Methyl-3-pyridinium)chlorocarbene tetrafluoroborate (MePyr(+)CCl BF4(-), 4) is
      generated by laser flash photolysis (LFP) of the corresponding diazirine (5) and
      reacted with tetramethylethylene, cyclohexene, 1-hexene, 2-ethyl-1-butene, methyl
      acrylate, and acrylonitrile. Absolute rate constants are measured for these
      carbene-alkene addition reactions, and activation parameters are obtained for
      additions of MePyr(+)CCl BF4(-) to tetramethylethylene, cyclohexene, and 1
      hexene. MePyr(+)CCl BF4(-) is computed to be a highly reactive, electrophilic,
      singlet carbene, and experiments are in accord with expectations. Its activation
      parameters are compared with those of CF3CCl, CCl2, CClF, and CF2. In all cases,
      enthalpy-entropy compensation is observed, with DeltaH(?) and DeltaS(?)
      decreasing in tandem as carbenic stability decreases. A qualitative explanation
      is offered for this phenomenon. 

PMID- 25845281
TI  - Discovery of new acylaminopyridines as GSK-3 inhibitors by a structure guided in
      depth exploration of chemical space around a pyrrolopyridinone core.
AB  - Glycogen synthase kinase-3 (GSK-3) has been proposed to play a crucial role in
      the pathogenesis of many diseases including cancer, stroke, bipolar disorders,
      diabetes and neurodegenerative diseases. GSK-3 inhibition has been a major area
      of pharmaceutical interest over the last two decades. A plethora of reports
      appeared recently on selective inhibitors and their co-crystal structures in GSK
      3beta. We identified several series of promising new GSK-3beta inhibitors from a
      coherent design around a pyrrolopyridinone core structure. A systematic
      exploration of the chemical space around the central spacer led to potent single
      digit and sub-nanomolar GSK-3beta inhibitors. When dosed orally in a transgenic
      mouse model of Alzheimer's disease (AD), an exemplary compound showed significant
      lowering of Tau phosphorylation at one of the GSK-3 phosphorylating sites,
      Ser396. X-ray crystallography greatly aided in validating the binding hypotheses.

PMID- 25845283
TI  - Risk of prostate cancer mortality in men with a history of prior cancer.
AB  - OBJECTIVES: To describe outcomes of patients with prostate cancer diagnosed after
      another malignancy and identify factors associated with prostate cancer death in
      this population, as little is known about the clinical significance of prostate
      cancer as a subsequent malignancy. PATIENTS AND METHODS: We studied 18 225 men
      diagnosed with prostate cancer after another malignancy from 1973 to 2006. We
      compared demographic and clinical variables, and the proportion of death from
      prostate cancer vs prior malignancy with t-test and chi-squared analyses. Fine
      and Gray's regression was used to consider the effect of treatment on prostate
      cancer death. We then studied a second cohort of 88 013 men with prostate cancer
      as a first or second malignancy to describe current diagnostic and treatment
      patterns. RESULTS: One in seven men died from prostate cancer in our first
      cohort. More died from prostate cancer following colorectal cancer (16.8% vs
      13.7%), melanoma (13.4% vs 7.56%), and oral cancer (19.1% vs 4.04%), but fewer
      following bladder cancer, kidney cancer, lung cancer, leukaemia and non-Hodgkin's
      lymphoma (all P < 0.001). Prostate cancer treatment was associated with a nearly
      50% lower risk of death when high-grade or high-stage (adjusted hazard ratio
      0.55, 95% confidence interval [CI] 0.47-0.64). Patients who died from prostate
      cancer had higher grade and stage disease, and received less treatment than
      patients who died from prior malignancy. The second cohort showed subsequent
      prostate cancer had more high-risk disease (36.3% vs 22.2%, P < 0.001) and less
      prostate cancer treatment (adjusted odds ratio 0.872, 95% CI 0.818-0.930) than
      primary prostate cancer. CONCLUSIONS: Prostate cancer remains a significant cause
      of mortality when diagnosed as a subsequent cancer. These results suggest
      prostate cancer treatment should be seriously considered in patients with prior
      malignancies, especially those with high-grade or locally advanced prostate
      cancer.

PMID- 25845289
TI  - The effectiveness of conservation interventions to overcome the urban
      environmental paradox.
AB  - Globally, urbanization is rapidly growing cities and towns at a historically
      unprecedented rate, and this rapid urban growth is influencing many facets of the
      environment. This paper reviews the effectiveness of conservation interventions
      that are designed to increase urban sustainability. It presents evidence for an
      apparent urban-environmental paradox: while the process of urban growth converts
      natural habitat to other land covers and degrades natural resources and ecosystem
      function, the increase in human population can increase demand for natural
      resources and ecosystem services. The fundamental problem that many conservation
      interventions try to address is that most facets of the environment are common or
      public goods, and are hence undervalued in decision making (market failure). The
      paper presents a threefold classification of conservation interventions in
      cities: conservation in the city (protecting biodiversity), conservation by the
      city (reducing per capita resource and energy use), and conservation for cities
      (projects that maintain or enhance ecosystem services). It ends by discussing
      methods for spatially targeting conservation interventions of all three types and
      for quantifying the effectiveness of interventions retrospectively.

PMID- 25845290
TI  - Prime-boost vaccination strategy with bacillus Calmette-Guerin (BCG) and
      liposomized alpha-crystalline protein 1 reinvigorates BCG potency.
AB  - Bacillus Calmette-Guerin (BCG) remains the only available and most widely
      administered vaccine against Mycobacterium tuberculosis (Mtb), yet it fails to
      protect vaccinated individuals either from primary infection or reactivation of
      latent tuberculosis (TB). Despite BCG's variable efficacy against TB, the fact
      remains that BCG imparts protection in children against the disease, indicating
      that BCG possesses a wide protective antigenic repertoire. However, its failure
      to impart protection in adulthood can be linked to its failure to generate long
      lived memory response and elicitation of an inadequate immune response against
      latency-associated antigens. Therefore, to improve the protective efficacy of
      BCG, a novel vaccination strategy is required. Consequently, in the present
      study, we have exploited the vaccination potential of liposomized alpha
      crystalline 1 (Acr1L), a latency-associated antigen to induce enduring protective
      immunity against Mtb in BCG-primed animals. It is noteworthy that an increase in
      the multi-functional [interferon (IFN)-gamma(hi) /tumour necrosis factor (TNF)
      alpha(hi) ] CD4 and CD8 T cells were observed in BCG-primed and Acr1L-boosted
      (BCG-Acr1L) animals, compared to BCG alone. Further, substantial expansion of
      both central memory (CD44(hi) /CD62L(hi) ) and effector memory (CD44(hi)
      /CD62L(lo) ) populations of CD4 and CD8 T cells was noted. Importantly, BCG-Acr1L
      exhibited significantly better protection than BCG, as evidenced by a reduction
      in the bacterial burden and histopathological data of the lungs. In essence, BCG
      Acr1L could be a potent future vaccination strategy to reinvigorate BCG potency. 

PMID- 25845291
TI  - The Kings Score refines prognostic prediction in hepatocellular carcinoma: a
      novel application.
AB  - BACKGROUND & AIMS: There are a number of prognostic scores in hepatocellular
      carcinoma (HCC), none of which is optimal in predicting overall survival (OS) in
      the individual patient, particularly in intermediate stage disease, where
      patients are not surgically treatable but may qualify for a wide range of
      palliative interventions. We evaluated the prognostic role of a biochemical
      algorithm, the Kings Score (KS), in the palliative setting of care. METHODS: We
      used the algorithm [age x AST x INR]/platelet count to derive the KS. Full
      clinical data including Barcelona Clinic Liver Cancer (BCLC) stage were studied
      in a training set of 97 patients from the UK. Independent predictors of survival
      identified in multivariate analysis were validated in an independent cohort of
      766 patients from Japan and Italy. RESULTS: In both training and validation sets,
      KS was confirmed as an independent predictor of OS (P < 0.01). Ad-hoc subgroup
      analysis revealed the KS to be prognostic in the palliative setting, being able
      to subclassify patients presenting with intermediate and advanced disease
      according to BCLC criteria (P < 0.001). CONCLUSION: The KS integrates into the
      BCLC system to improve prognostic substratification in the palliative setting of
      care. The KS may help reducing disease heterogeneity and refine treatment
      allocation in intermediate-advanced HCC.

PMID- 25845292
TI  - Integrated whole-genome screening for Pseudomonas aeruginosa virulence genes
      using multiple disease models reveals that pathogenicity is host specific.
AB  - Pseudomonas aeruginosa is a multi-host opportunistic pathogen causing a wide
      range of diseases because of the armoury of virulence factors it produces, and it
      is difficult to eradicate because of its intrinsic resistance to antibiotics.
      Using an integrated whole-genome approach, we searched for P. aeruginosa
      virulence genes with multi-host relevance. We constructed a random library of 57
      360 Tn5 mutants in P. aeruginosa PAO1-L and screened it in vitro for those
      showing pleiotropic effects in virulence phenotypes (reduced swarming, exo
      protease and pyocyanin production). A set of these pleiotropic mutants were
      assayed for reduced toxicity in Drosophila melanogaster, Caenorhabditis elegans,
      human cell lines and mice. Surprisingly, the screening revealed that the
      virulence of the majority of P. aeruginosa mutants varied between disease models,
      suggesting that virulence is dependent on the disease model used and hence the
      host environment. Genomic analysis revealed that these virulence-related genes
      encoded proteins from almost all functional classes, which were conserved among
      P. aeruginosa strains. Thus, we provide strong evidence that although P.
      aeruginosa is capable of infecting a wide range of hosts, many of its virulence
      determinants are host specific. These findings have important implication when
      searching for novel anti-virulence targets to develop new treatments against P.
      aeruginosa. 

PMID- 25845293
TI  - Serum biochemistry reference intervals of live wild dugongs (Dugong dugon) from
      urban coastal Australia.
AB  - BACKGROUND: Little is known about the baseline clinical pathology of the dugong
      (Dugong dugon), a vulnerable marine mammal found in tropical coastal marine
      systems. OBJECTIVES: The purpose of the study was to collect and determine
      reference intervals (RI) for select serum biochemical variables for dugongs, and
      to analyze differences between males and females and different age groups.
      METHODS: Reference intervals were established from 103 apparently healthy, wild
      caught dugongs for 31 analytes using a Beckman Coulter AU400 Automated Chemistry
      Analyzer and an Olympus AU680 Chemistry-Immuno Analyzer. RESULTS: Significant
      differences (P < .05) in some of the variables were found related to size class,
      sex, and pregnancy status. Adult dugongs had higher serum sodium, potassium,
      bicarbonate, glucose, and l-lactate concentrations and higher anion gap, compared
      to sub-adults. Male dugongs had higher triglyceride and l-lactate concentrations
      than females. Pregnant females displayed higher l-lactate levels compared to
      nonpregnant animals. Statistical differences in variables within the population
      contributed to better understanding of the physiologic differences between
      cohorts. Some serum biochemistry changes observed in this study here also
      potentially include some effects of pursuit on dugongs (eg, higher l-lactate);
      however, as all dugongs were subject to similar capture and handling, serum
      biochemistry RI should be considered as normal for captured dugongs. CONCLUSIONS:
      The serum biochemical RI documented here are considered representative of a
      population of healthy captured dugongs. They provide a baseline for health
      surveillance of this and other dugong populations.

PMID- 25845294
TI  - Pathophysiology and treatment of typical and atypical hemolytic uremic syndrome.
AB  - Hemolytic uremic syndrome is a rare disease, frequently responsible for renal
      insufficiency in children. Recent findings have led to renewed interest in this
      pathology. The discovery of new gene mutations in the atypical form of HUS and
      the experimental data suggesting the involvement of the complement pathway in the
      typical form, open new perspectives for treatment. This review summarizes the
      current state of knowledge on both typical and atypical hemolytic uremic syndrome
      pathophysiology and examines new perspectives for treatment. 

PMID- 25845295
TI  - Inhibitory action of novel hydrogen sulfide donors on bovine isolated posterior
      ciliary arteries.
AB  - In the present study, we investigate the inhibitory effect of novel H2S donors,
      AP67 and AP72 on isolated bovine posterior ciliary arteries (PCAs) under
      conditions of tone induced by an adrenoceptor agonist. Furthermore, we examined
      the possible mechanisms underlying the AP67- and AP72-induced relaxations.
      Isolated bovine PCA were set up for measurement of isometric tension in organ
      baths containing oxygenated Krebs solution. The relaxant action of H2S donors was
      studied on phenylephrine-induced tone in the absence or presence of enzyme
      inhibitors for the following pathways: cyclooxygenase (COX); H2S; nitric oxide
      and the ATP-sensitive K(+) (KATP) channel. The H2S donors, NaSH (1 nM - 10 MUM),
      AP67 (1 nM - 10 MUM) and AP72 (10 nM - 1 MUM) elicited a concentration-dependent
      relaxation of phenylephrine-induced tone in isolated bovine PCA. While the COX
      inhibitor, flurbiprofen (3 MUM) blocked significantly (p < 0.05) the inhibitory
      response elicited by AP67, it had no effect on relaxations induced by NaSH and
      AP72. Both aminooxyacetic acid (30 MUM) and propargylglycine (1 mM), enzyme
      inhibitors of H2S biosynthesis caused significant (p < 0.05) rightward shifts in
      the concentration-response curve to AP67 and AP72. Furthermore, the KATP channel
      antagonist, glibenclamide (300 MUM) and the NO synthase inhibitor, l-NAME (100
      MUM) significantly attenuated (p < 0.05) the relaxation effect induced by AP67
      and AP72 on PCA. We conclude that H2S donors can relax pre-contracted isolated
      bovine PCA, an effect dependent on endogenous production of H2S. The inhibitory
      action of only AP67 on pre-contracted PCA may involve the production of
      inhibitory endogenous prostanoids. Furthermore, the observed inhibitory action of
      H2S donors on PCA may depend on the endogenous biosynthesis of NO and by an
      action of KATP channels. 

PMID- 25845296
TI  - Pediatric Cutaneous Nontuberculous Mycobacterium Infections in Singapore.
AB  - BACKGROUND: Nontuberculous mycobacterium (NTM) infections are rare in children,
      with limited published studies. The course of the disease can be variable and
      there are no accepted treatment guidelines for the management of NTM infections
      in children. OBJECTIVE: To review a cohort of pediatric patients admitted to a
      tertiary pediatric hospital in Singapore for cutaneous NTM infections. METHODS: A
      retrospective review was performed of all children admitted to KK Women's and
      Children's Hospital with cutaneous NTM infections from 2002 to 2012. RESULTS:
      Sixty-seven patients with positive NTM cultures from various body sites were
      identified. Eight of the 67 patients (11.9%) presented with cutaneous NTM without
      evidence of systemic involvement. The mean age at diagnosis for these eight
      patients was 10 years (range 5-21 yrs). Mycobacterium abscessus was the most
      common NTM isolated (five patients), followed by Mycobacterium hemophilium (two
      patients) and Mycobacterium kansasii (one patient). Most patients presented with
      isolated skin abscesses. Two patients were immunocompromised. Six patients
      required multidrug antibiotic treatment for a median duration of 5.5 months
      (range 3-17 mos). The median follow-up duration was 8.5 months (range 2 wks-29
      mos). CONCLUSION: Although the incidence of cutaneous NTM is rare, the diagnosis
      should be considered in patients presenting with chronic wounds. Most patients
      require treatment with multidrug antibiotic therapy, although uncomplicated
      abscesses can be treated with surgical incision and drainage alone.

PMID- 25845297
TI  - Management of diabetic nephropathy: Recent progress and future perspective.
AB  - Diabetic nephropathy (DN), a leading cause of end-stage renal disease (ESRD)
      affecting ~20-30% diabetics, is associated with increased cardiovascular
      mortality. The progression of kidney disease in patients with diabetes can take
      many years. It occurs as a result of interaction between both genetic and
      environmental factors in individuals with both type 1 and type 2 diabetes.
      Hyperglycaemia, hypertension, and genetic pre-disposition are the main risk
      factors besides elevated serum lipids, smoking habits, and the amount of dietary
      proteins. Interventions such as glycaemic control, blood pressure control and
      inhibition of the renin-angiotensin-aldosterone system have been shown to slow
      this progression. Despite the implementation of these strategies, the number of
      patients with diabetes that ultimately develop end-stage renal disease remains
      high. The treatment of DN, therefore, has posed a formidable challenge besides
      optimization of renin-angiotensin-aldosterone system blockade in patients with
      DN; additional investigation has focused on the potential of novel therapies that
      target various pathways upregulated by hyperglycaemia or other targets believed
      to promote the progression of DN such as oxidative stress, inflammation,
      endothelin system and vitamin D receptors. This review article addresses the
      pathogenesis and some of the well established principles regarding the
      progression and accepted management of DN, and also includes the perspectives of
      novel anti-DN agents and the future directions for the prevention of DN. 

PMID- 25845298
TI  - Multiparametric characterisation of neuronal network activity for in vitro
      agrochemical neurotoxicity assessment.
AB  - The last few decades have seen the marketing of hundreds of new pesticide
      products with a forecasted expansion of the global agrochemical industry. As
      several pesticides directly target nervous tissue as their mechanism of toxicity,
      alternative methods to routine in vivo animal testing, such as the Multi
      Electrode Array (MEAs)-based approach, have been proposed as an in vitro tool to
      perform sensitive, quick and low cost neuro-toxicological screening. Here, we
      examined the effects of a training set of eleven active substances known to have
      neuronal or non-neuronal targets, contained in the most commonly used
      agrochemicals, on the spontaneous electrical activity of cortical neuronal
      networks grown on MEAs. A multiparametric characterisation of neuronal network
      firing and bursting was performed with the aim of investigating how this can
      contribute to the efficient evaluation of in vitro chemical-induced
      neurotoxicity. The analysis of MFR, MBR, MBD, MISI_B and % Spikes_B parameters
      identified four different groups of chemicals: one wherein only inhibition is
      observed (chlorpyrifos, deltamethrin, orysastrobin, dimoxystrobin); a second one
      in which all parameters, except the MISI_B, are inhibited (carbaryl, quinmerac);
      a third in which increases at low chemical concentration are followed by
      decreases at high concentration, with exception of MISI_B that only decreased
      (fipronil); a fourth in which no effects are observed (paraquat, glyphosate,
      imidacloprid, mepiquat). The overall results demonstrated that the
      multiparametric description of the neuronal networks activity makes MEA-based
      screening platform an accurate and consistent tool for the evaluation of the
      toxic potential of chemicals. In particular, among the bursting parameters the
      MISI_B was the best that correlates with potency and may help to better define
      chemical toxicity when MFR is affected only at relatively high concentration. 

PMID- 25845299
TI  - Potential of casein as a nutrient intervention to alleviate lead (Pb) acetate
      mediated oxidative stress and neurotoxicity: First evidence in Drosophila
      melanogaster.
AB  - Understanding the interaction between dietary protein deficits and neurotoxicants
      such as lead (Pb) is critical since oxidative stress is a common denominator
      under such conditions. The Drosophila system is an extensively used model to
      investigate the interaction between nutrients and environmental toxicants.
      Accordingly, we have examined the hypothesis that casein (CSN) enrichment has the
      propensity to attenuate Pb-associated phenotype, oxidative stress and
      neurotoxicity in Drosophila melanogaster. Exposure of young (2-3 d) and adult
      flies (10-12 d old) to Pb acetate (0-20 mM, 7 d) in the medium resulted in a
      concentration dependent mortality and the survivors exhibited a hyperactive
      phenotype. While males showed higher susceptibility to Pb among both age groups,
      young flies were relatively more susceptible than adults. Pb exposure (5-10 mM, 5
      d) among young flies caused robust oxidative stress as evidenced by markedly
      elevated levels of reactive oxygen species with concomitant perturbations in the
      activities of antioxidant enzymes (diminished SOD and elevated thioredoxin
      reductase) and altered redox state. Further, Pb caused significant elevation in
      the activity of acetylcholinesterase and dopamine levels. In a satellite study,
      we assessed the modulatory effect of CSN-enriched diet (1-2%) on Pb intoxication
      in terms of lethality, hyperactivity, oxidative stress and neurotoxicity. CSN
      markedly offset Pb-induced lethality and diminished the hyperactivity response.
      While CSN enrichment among Pb (5 mM) treated flies caused further elevation in
      ROS levels and thioredoxin reductase activity, the SOD levels were restored to
      normalcy. Further, CSN improved the activity levels of complex I-III and restored
      the dopamine levels. Our data suggest that Pb-induced toxicity in the Drosophila
      system may be predominantly mediated through oxidative stress mechanisms and the
      propensity of casein-enriched diet to abrogate such responses. Hence, we propose
      that enrichment of diet with protein such as casein may be a useful approach to
      alleviate Pb associated adverse effects in children.

PMID- 25845301
TI  - Synthesis of dithienogermole-containing oligo- and polysilsesquioxanes as
      luminescent materials.
AB  - Dithienogermole (DTG)-containing oligo- and polysilsesquioxanes were prepared by
      hydrolysis/condensation of DTGs bearing one () or two trialkoxysilyl group(s) ().
      The reaction of gave a cage-type octasilsesquioxane with eight DTG groups at the
      edges () as a viscous oil, whereas the reaction of yielded a network polymer ()
      as a self-standing film. showed a photoluminescence (PL) quantum yield (Phi) of
      56% in THF. This value was as high as that of (Phi = 58%), in spite of the
      accumulation of DTG units in the molecule, as characteristics of the POSS
      structure. The PL of in THF was suppressed by contact with nitrobenzene, showing
      the potential of for sensing nitroaromatic explosives. Polymer exhibited a
      relatively low Phi of 2% as a film, but Phi was improved to 38% by
      copolymerization with trimethoxymethylsilane. was also copolymerized with a
      trimethoxysilyl-substituted carbazole derivative () to provide
      polysilsesquioxanes with DTG and carbazole units, which showed efficient photo
      energy transfer from carbazole to DTG in the films. Similar copolymerization of
      with in the presence of poly(9-vinylcarbazole) provided a composite material with
      hole-transporting electroluminescence properties, applicable in multi-layered
      organic light emitting diodes. 

PMID- 25845300
TI  - Allopurinol reduces severity of delayed neurologic sequelae in experimental
      carbon monoxide toxicity in rats.
AB  - Approximately half of those who survive severe carbon monoxide (CO) poisoning
      develop delayed neurologic sequelae. Growing evidence supports the crucial role
      of free radicals in delayed brain injury associated with CO toxicity. Xanthine
      oxidase (XO) has been reported to play a pivotal role in the generation of
      reactive oxygen species (ROS) in CO poisoning. A recent report indicates that
      allopurinol both attenuated oxidative stress and possessed anti-inflammatory
      properties in an animal model of acute liver failure. In this study, we aimed to
      explore the potential of allopurinol to reduce the severity of delayed neurologic
      sequelae. The rats were first exposed to 1000 ppm CO for 40 min and then to 3000
      ppm CO for another 20 min. Following CO poisoning, the rats were injected with
      allopurinol (50 mg/kg, i.p.) six times. Results showed that allopurinol
      significantly reduced neuronal death and suppressed expression of pro
      inflammatory factors, including tumor necrosis factor-alpha, intercellular
      adhesion molecule-1, ionized calcium-binding adapter molecule 1, and degraded
      myelin basic protein. Furthermore, behavioral studies revealed an improved
      performance in the Morris water maze test. Our findings indicated that
      allopurinol may have protective effects against delayed neurologic sequelae
      caused by CO toxicity.

PMID- 25845302
TI  - A prospective randomised trial comparing mesh types and fixation in totally
      extraperitoneal inguinal hernia repairs.
AB  - The totally extraperitoneal (TEP) approach for surgical repair of inguinal
      hernias has emerged as a popular technique. We conducted a prospective randomised
      trial to compare patient comfort scores using different mesh types and fixation
      using this technique. Over a 14 month period, 146 patients underwent 232 TEP
      inguinal hernia repairs. We compared the comfort scores of patients who underwent
      these procedures using different types of mesh and fixation. A non-absorbable 15
      * 10 cm anatomical mesh fixed with absorbable tacks (Control group) was compared
      with either a non-absorbable 15 * 10 cm folding slit mesh with absorbable tacks
      (Group 2), a partially-absorbable 15 * 10 cm mesh with absorbable tacks (Group 3)
      or a non-absorbable 15 * 10 cm anatomical mesh fixed with 2 ml fibrin sealant
      (Group 4). Outcomes were compared at 1, 2, 4 and 12 weeks using the Carolina
      Comfort Scale (CCS) scores. At 1, 2, 4 and 12 weeks, the median global CCS scores
      were low for all treatment groups. Statistically significant differences were
      seen only for median CCS scores and subscores with the use of partially
      absorbable mesh with absorbable tacks (Group 3) at weeks 2 and 4. However, these
      were no longer significant at week 12. In this study, the TEP inguinal hernia
      repair with minimal fixation results in low CCS scores. There were no statistical
      differences in CCS scores when comparing types of mesh, configuration of the mesh
      or fixation methods.

PMID- 25845303
TI  - The obesity-related FTO gene variant associates with the risk of recurrent
      miscarriage.
AB  - OBJECTIVE: To investigate the association of the fat mass and obesity associated
      gene (FTO) rs9939609 single nucleotide polymorphism with recurrent miscarriage.
      DESIGN: Candidate gene association study. SETTING: Human Genetics Unit, Colombo,
      Sri Lanka. POPULATION: A total of 202 Sinhalese women with two or more first
      trimester miscarriages and no living children (cases) and 202 age- and ethnicity
      matched women with no history of miscarriage and having two or more living
      children (controls). METHODS: Peripheral blood was collected from the
      participants and DNA was extracted. Genotyping was performed at the Australian
      genome Research Facility using the Sequenom MassARRAY system. Genotype and allele
      frequencies of cases were compared with controls using chi-squared testing. MAIN
      OUTCOME MEASURES: The prevalence of the single nucleotide polymorphism in cases
      and controls. RESULTS: The mean age of the women in the recurrent miscarriage
      group was 31.9 +/- 0.4 years and that of the control group was 32.3 +/- 0.3
      years. Of the women in the recurrent miscarriage group, 140 (69.3%) had
      experienced three or more first-trimester miscarriages. The prevalence of the AA
      genotype [p = 0.0002, odds ratio (95% CI) = 3.8 (1.8-8.0)] and A allele [p =
      0.002, odds ratio (95% CI) = 1.6 (1.2-2.2)] of the FTO rs9939609 single
      nucleotide polymorphism were increased in women in the recurrent miscarriage
      group compared with the control group. CONCLUSION: The obesity-related FTO
      rs9939609 single nucleotide polymorphism associates with recurrent miscarriage.
      This finding warrants further investigation with controlling for important
      factors such as body mass index, diabetes and cardiovascular disease status. The
      single nucleotide polymorphism may be useful in predicting the risk of recurrent
      miscarriage.

PMID- 25845304
TI  - Engineering biological systems toward a sustainable bioeconomy.
AB  - The nature of our major global risks calls for sustainable innovations to
      decouple economic growth from greenhouse gases emission. The development of
      sustainable technologies has been negatively impacted by several factors
      including sugar production costs, production scale, economic crises, hydraulic
      fracking development and the market inability to capture externality costs.
      However, advances in engineering of biological systems allow bridging the gap
      between exponential growth of knowledge about biology and the creation of
      sustainable value chains for a broad range of economic sectors. Additionally,
      industrial symbiosis of different biobased technologies can increase
      competitiveness and sustainability, leading to the development of eco-industrial
      parks. Reliable policies for carbon pricing and revenue reinvestments in
      disruptive technologies and in the deployment of eco-industrial parks could boost
      the welfare while addressing our major global risks toward the transition from a
      fossil to a biobased economy. 

PMID- 25845305
TI  - Deletion of hxk1 gene results in derepression of xylose utilization in
      Scheffersomyces stipitis.
AB  - A major problem in fermenting xylose in lignocellulosic substrates is the
      presence of glucose and mannose which inhibit xylose utilization. Previous
      studies showed that catabolite repression in some yeasts is associated with
      hexokinases and that deletion of one of these gene(s) could result in derepressed
      mutant strain(s). In this study, the hxk1 encoding hexokinase 1 in
      Scheffersomyces stipitis was disrupted. The ?hxk1 SS6 strain retained the ability
      to utilize the main hexoses and pentoses commonly found in lignocellulosic
      hydrolysates as efficiently as the wild-type (WT) strain. SS6 also fermented the
      dominant sugars to ethanol; however, on xylose, the ?hxk1 strain produced more
      xylitol and less ethanol than the WT. On mixed sugars, as expected the WT
      utilized glucose ahead of xylose and xylose utilization did not commence until
      all the glucose was consumed. In contrast, the ?hxk1 mutant showed derepression
      in that it started to utilize xylose even when considerable glucose (about 1.72%,
      w/v) remained in the medium. Similarly, mannose did not repress xylose
      utilization by the ?hxk1 mutant and xylose and mannose were simultaneously
      utilized. The results are of interest in efforts to engineer yeast strains
      capable of efficiently utilizing glucose and xylose simultaneously for
      lignocellulosic biomass conversion.

PMID- 25845306
TI  - Investigating the influence of long-range transport on surface O3 in Nevada, USA,
      using observations from multiple measurement platforms.
AB  - The current United States (US) National Ambient Air Quality Standard (NAAQS) for
      O3 (75 ppb) is expected to be revised to between 60 and 70 ppb. As the NAAQS
      becomes more stringent, characterizing the extent of O3 and precursors
      transported into the US is increasingly important. Given the high elevation,
      complex terrain, and location in the Intermountain West, the State of Nevada is
      ideally situated to intercept air transported into the US. Until recently,
      measurements of O3 and associated pollutants were limited to areas in and around
      the cities of Las Vegas and Reno. In 2011, the Nevada Rural Ozone Initiative
      began and through this project 13 surface monitoring sites were established. Also
      in 2011, the NASA Ames Alpha Jet Atmospheric eXperiment (AJAX) began making
      routine aircraft measurements of O3 and other greenhouse gases in Nevada. The
      availability of aircraft and surface measurements in a relatively rural, remote
      setting in the Intermountain West presented a unique opportunity to investigate
      sources contributing to the O3 observed in Nevada. Our analyses indicate that
      stratosphere to troposphere transport, long-range transport of Asian pollution,
      and regional emissions from urban areas and wildfires influence surface
      observations. The complexity of sources identified here along with the fact that
      O3 frequently approaches the threshold being considered for a revised NAAQS
      indicate that interstate and international cooperation will be necessary to
      achieve compliance with a more stringent regulatory standard. Further, on a
      seasonal basis we found no significant difference between daily 1-h maximum O3 at
      surface sites, which ranged in elevation from 888 to 2307 m, and aircraft
      measurements of O3 <2500 m which suggests that similar processes influence
      daytime O3 across rural Nevada and indicates that column measurements from
      Railroad Valley, NV are useful in understanding these processes.

PMID- 25845307
TI  - Management of acne vulgaris with hormonal therapies in adult female patients.
AB  - Acne vulgaris is a very common condition affecting up of 93% of adolescents.
      Although rare, this disease may persist in adulthood. In adult women with acne
      (those older than 25 years old), this condition is particularly relevant because
      of the refractory to conventional therapies, which makes acne a challenge for
      dermatologists in this group of patients. In order to its potential risk for
      chronicity and the involvement of visible anatomical sites such as face and upper
      torso, acne has been associated with a wide spectrum of psychological and social
      dysfunction such as depression, anxiety, suicidal ideation, somatization, and
      social inhibition. In particular, adult women with acne have been shown to be
      adversely impacted by the effect of acne on their quality of life. For the last
      four decades, dermatologists have used hormonal therapies for the management of
      acne vulgaris in adult women, which are considered a rational choice given the
      severity and chronicity of this condition in this group of patients. The aim of
      this work is to review the hormonal drugs for management of acne. 

PMID- 25845308
TI  - The performance of three mortality risk-adjustment comorbidity indices in a
      community epilepsy cohort.
AB  - Mortality risk-adjustment comorbidity indices are an efficient means of
      controlling for the important confounding effect of somatic and psychiatric
      comorbidities in observational mortality studies. We carried out an external
      validation study and compared the performance of the Charlson, Elixhauser and
      Epilepsy-specific (ES) indices using the National General Practice Study of
      Epilepsy, a community-based prospective cohort of 558 people with incident
      epilepsy followed for 23.3 years (median). The minimum and maximum crude
      mortality rates were similar between the three indices, but mid-range Elixhauser
      scores predicted lower rates relative to the two other indices. Two of the
      stratified Charlson Kaplan-Meier survival probability curves crossed, and a low
      Elixhauser score was associated with a counterintuitive increase in mortality.
      Each comorbidity index was a significant predictor of mortality in the Cox
      proportional hazards models, although there was evidence that the unadjusted
      Charlson regression model violated the proportionality assumption. Harrell's c
      statistics were >0.87 in all adjusted models. All three indices performed well,
      but there is evidence that the ES index may be more discriminating and have a
      better model fit than the Charlson or Elixhauser indices in a community-based
      clinical cohort of people with epilepsy.

PMID- 25845309
TI  - Biophysical characterization of KV3.1 potassium channel activating compounds.
AB  - The effect of two positive modulators, RE1 and EX15, on the voltage-gated K(+)
      channel Kv3.1 was investigated using the whole-cell patch-clamp technique on
      HEK293 cells expressing Kv3.1a. RE1 and EX15 increased the Kv3.1 currents in a
      concentration-dependent manner with an EC50 value of 4.5 and 1.3uM, respectively.
      However, high compound concentrations caused an inhibition of the Kv3.1 current.
      The compound-induced activation of Kv3.1 channels showed a profound
      hyperpolarized shift in activation kinetics. 30uM RE1 shifted V1/2 from 5.63+/
      0.31mV to -9.71+/-1.00mV and 10uM EX15 induced a shift from 10.77+/-0.32mV to 
      15.11+/-1.57mV. The activation time constant (Tauact) was reduced for both RE1
      and EX15, with RE1 being the fastest activator. The deactivation time constant
      (Taudeact) was also markedly reduced for both RE1 and EX15, with EX15 inducing
      the most prominent effect. Furthermore, subjected to depolarizing pulses at 30Hz,
      both compounds were showing a use-dependent effect resulting in a reduction of
      the compound-mediated effect. However, during these conditions, RE1- and EX15
      modified current amplitudes still exceeded the control condition amplitudes by up
      to 200%. In summary, the present study introduces the first detailed biophysical
      characterization of two new Kv3.1 channel modifying compounds with different
      modulating properties. 

PMID- 25845310
TI  - Simultaneous Synchrotron WAXD and Fast Scanning (Chip) Calorimetry: On the
      (Isothermal) Crystallization of HDPE and PA11 at High Supercoolings and Cooling
      Rates up to 200  degrees C s(-1).
AB  - An experimental setup, making use of a Flash DSC 1 prototype, is presented in
      which materials can be studied simultaneously by fast scanning calorimetry (FSC)
      and synchrotron wide angle X-ray diffraction (WAXD). Accumulation of multiple,
      identical measurements results in high quality, millisecond WAXD patterns.
      Patterns at every degree during the crystallization and melting of high density
      polyethylene at FSC typical scanning rates from 20 up to 200  degrees C s(-1) are
      discussed in terms of the temperature and scanning rate dependent material
      crystallinities and crystal densities. Interestingly, the combined approach
      reveals FSC thermal lag issues, for which can be corrected. For polyamide 11,
      isothermal solidification at high supercooling yields a mesomorphic phase in less
      than a second, whereas at very low supercooling crystals are obtained. At
      intermediate supercooling, mixtures of mesomorphic and crystalline material are
      generated at a ratio proportional to the supercooling. This ratio is constant
      over the isothermal solidification time. 

PMID- 25845311
TI  - Polarized trafficking provides spatial cues for planar cell polarization within a
      tissue.
AB  - Planar cell polarity, the polarization of cells within the plane of the
      epithelium, orthogonal to the apical-basal axis, is essential for a growing list
      of developmental events, and - over the last 15 years - has evolved from a little
      studied curiosity in Drosophila to the subject of a substantial research
      enterprise. In that time, it has been recognized that two molecular systems are
      responsible for polarization of most tissues: Both the "core" Frizzled system and
      the "global" Fat/Dachsous/Four-jointed system produce molecular asymmetry within
      cells, and contribute to morphological polarization. In this review, we discuss
      recent findings on the molecular mechanism that links "global" directional
      signals with local coordinated polarity. 

PMID- 25845312
TI  - Persistence of poor sleep predicts the severity of the clinical condition after
      6months of standard treatment in patients with eating disorders.
AB  - Clinical evidence suggests that eating disorder (ED) patients experience poor
      sleep even if they rarely complain of it. However, direct empirical evidence
      supporting this relationship is still sparse. In order to provide direct
      evidence, poor sleep, severity of the ED symptoms and depression were obtained in
      562 ED patients at treatment admission (T0). For 271 patients out of them, data
      were also available after 6months of standard treatment (T1). Results evidence
      that at T0 poor sleep predicts severity of ED symptoms through the mediation of
      depression. Persistence of poor sleep at T1 directly predicts the severity of the
      ED symptoms both directly and through the mediation of depression. These findings
      suggest that the treatment of ED may benefit from addressing poor sleep since its
      presence and persistence increase comorbidity and attrition to the standard
      treatment. 

PMID- 25845313
TI  - Neurotoxicity of cerebro-spinal fluid from patients with Parkinson's disease on
      mesencephalic primary cultures as an in vitro model of dopaminergic neurons.
AB  - Parkinson's disease is a degenerative disorder of the central nervous system. In
      spite of extensive research, neither the cause nor the mechanisms have been
      firmly established thus far. One assumption is that certain toxic substances may
      exist in the cerebro-spinal fluid (CSF) of Parkinson's disease patients. To
      confirm the neurotoxicity of CSF and study the potential correlation between
      neurotoxicity and the severity of Parkinson's disease, CSF was added to cultured
      cells. By observation of cell morphology, changes in the levels of lactate
      dehydrogenase, the ratio of tyrosine hydroxylase-positive cells, and the
      expression of tyrosine hydroxylase mRNA and protein, the differences between the
      two groups were shown. The created in vitro model of dopaminergic neurons using
      primary culture of mouse embryonic mesencephalic tissue is suitable for the study
      of neurotoxicity. The observations of the present study indicated that CSF from
      Parkinson's disease patients contains factors that can cause specific injury to
      cultured dopaminergic neurons. However, no obvious correlation was found between
      the neurotoxicity of CSF and the severity of Parkinson's disease.

PMID- 25845314
TI  - Association between suicidal ideation and exposure to suicide in social
      relationships among family, friend, and acquaintance survivors in South Korea.
AB  - Exposure to suicide in social relationships may be associated with suicidal
      ideation among survivors. In South Korea, which is known for having the highest
      suicide rate among OECD countries, exposure to suicide in social relationships
      can have serious consequences as social relationships are greatly emphasized in
      the society. The purpose of this study was to examine the association between
      survivors' suicidal ideation and their exposure to suicide in close
      relationships. Data collected through a telephone survey of a total of 1,000 men
      and women selected from across the nation using a stratified sampling method were
      analyzed. The results show that individuals who lost a family member, friend, or
      acquaintance in their lifetime are 4.5 times, 3.7 times, 2.2 times, respectively,
      more likely to have suicidal ideation in the past year compared to those without
      such experience. These findings suggest that special intervention for suicide
      survivors should be considered for those who experience suicide in close
      relationships. 

PMID- 25845315
TI  - Pharmacometric Models for Characterizing the Pharmacokinetics of Orally Inhaled
      Drugs.
AB  - During the last decades, the importance of modeling and simulation in clinical
      drug development, with the goal to qualitatively and quantitatively assess and
      understand mechanisms of pharmacokinetic processes, has strongly increased.
      However, this increase could not equally be observed for orally inhaled drugs.
      The objectives of this review are to understand the reasons for this gap and to
      demonstrate the opportunities that mathematical modeling of pharmacokinetics of
      orally inhaled drugs offers. To achieve these objectives, this review (i)
      discusses pulmonary physiological processes and their impact on the
      pharmacokinetics after drug inhalation, (ii) provides a comprehensive overview of
      published pharmacokinetic models, (iii) categorizes these models into
      physiologically based pharmacokinetic (PBPK) and (clinical data-derived)
      empirical models, (iv) explores both their (mechanistic) plausibility, and (v)
      addresses critical aspects of different pharmacometric approaches pertinent for
      drug inhalation. In summary, pulmonary deposition, dissolution, and absorption
      are highly complex processes and may represent the major challenge for modeling
      and simulation of PK after oral drug inhalation. Challenges in relating systemic
      pharmacokinetics with pulmonary efficacy may be another factor contributing to
      the limited number of existing pharmacokinetic models for orally inhaled drugs.
      Investigations comprising in vitro experiments, clinical studies, and more
      sophisticated mathematical approaches are considered to be necessary for
      elucidating these highly complex pulmonary processes. With this additional
      knowledge, the PBPK approach might gain additional attractiveness. Currently,
      (semi-)mechanistic modeling offers an alternative to generate and investigate
      hypotheses and to more mechanistically understand the pulmonary and systemic
      pharmacokinetics after oral drug inhalation including the impact of pulmonary
      diseases. 

PMID- 25845316
TI  - Relevance of using a compressive preload in the cervical spine: an experimental
      and numerical simulating investigation.
AB  - Simulating compressive action of muscles, a follower load attends to reproduce a
      more physiological biomechanical behaviour of the cervical spine. Only few
      experimental studies reported its influence on kinematics and intradiscal
      pressure in the cervical spine. STUDY DESIGN: In vitro human cadaveric and
      numerical simulating evaluation of a compressive preload in the cervical spine.
      OBJECTIVES: To analyse the influence of a compressive follower preload on the
      biomechanical behaviour of the cervical spine. METHODS: The present study was
      divided into two parts: part 1: in vitro investigation; part 2: numerical
      simulating analysis. Part 1: Twelve human cadaveric spines from C2 to T2 were
      evaluated intact and after application of a 50-N follower load. All tests were
      performed under load control by applying pure moments loading of 2 Nm in
      flexion/extension (FE), axial rotation (AR) and lateral bending (LB). Three
      dimensional displacements were measured using an optoelectronic system, and
      intradiscal pressures were measured at two levels. Part 2: Using a 3D finite
      element model, we evaluated the influence of a 50- and 100-N compressive preload
      on intradiscal loads, facets forces and ranges of motion. Different positions of
      the follower load along the anteroposterior axis (+/-5 mm) were also simulated.
      RESULTS: Part 1: Mean variation of cervical lordosis was 5 degrees  +/- 3 degrees
      . The ROM slightly increased in FE, whereas it consistently decreased in AR and
      LB. Coupled lateral bending during AR was also reduced. Increase in hysteresis
      was observed on load-displacement curves only for AR and LB. Intradiscal
      pressures increased, but the aspect of load-pressure curves was altered in AR and
      LB. Part 2: Using the FE model, only minimal changes in ROM were noted following
      the simulation of a 50-N compressive load for the three loading conditions.
      Compared to intact condition, <10% variation was observed with regard to the
      different magnitude and positioning simulated. Intradiscal loads and facets
      forces were systematically increased by applying compressive preload.
      CONCLUSIONS: Although the follower load represents an attractive option to apply
      compressive preload during experimental tests, we found that this method could
      affect the native biomechanical behaviour of spine specimen depending on which
      movement was considered. Only minimal effects were observed in FE, whereas
      significant changes in kinematics and intradiscal pressures were observed for AR
      and LB.

PMID- 25845317
TI  - [Genetic diversity and immunological characteristics of malignant melanoma: the
      therapeutic spectrum].
AB  - Malignant melanoma, originating from pigment cells, is a highly aggressive tumour
      affecting patients of any age group. Its incidence is rapidly growing. The most
      common form can be easily diagnosed by any physician. There are some well-known
      genetic (skin-, eye-, hair colour, naevi, melanoma in the personal/family
      history) and environmental (ultraviolet radiation) predisposing factors.
      Treatment is based on early diagnosis and excision. When metastasis occurs, the
      traditional chemo- and radiotherapy gives a low response rate. Recently some
      newly approved targeted therapies and immunomodulant drugs have become available.
      This review focuses on the classification and novel therapeutic approaches of
      malignant melanoma to provide guidance to clinicians.

PMID- 25845318
TI  - [Prognostic value of absolute monocyte count in chronic lymphocytic leukaemia].
AB  - INTRODUCTION: The low peripheral absolute lymphocyte and high monocyte count have
      been reported to correlate with poor clinical outcome in various lymphomas and
      other cancers. However, a few data known about the prognostic value of absolute
      monocyte count in chronic lymphocytic leukaemia. AIM: The aim of the authors was
      to investigate the impact of absolute monocyte count measured at the time of
      diagnosis in patients with chronic lymphocytic leukaemia on the time to treatment
      and overal survival. METHOD: Between January 1, 2005 and December 31, 2012, 223
      patients with newly-diagnosed chronic lymphocytic leukaemia were included. The
      rate of patients needing treatment, time to treatment, overal survival and causes
      of mortality based on Rai stages, CD38, ZAP-70 positivity and absolute monocyte
      count were analyzed. RESULTS: Therapy was necessary in 21.1%, 57.4%, 88.9%, 88.9%
      and 100% of patients in Rai stage 0, I, II, III an IV, respectively; in 61.9% and
      60.8% of patients exhibiting CD38 and ZAP-70 positivity, respectively; and in
      76.9%, 21.2% and 66.2% of patients if the absolute monocyte count was <0.25 G/l,
      between 0.25-0.75 G/l and >0.75 G/l, respectively. The median time to treatment
      and the median overal survival were 19.5, 65, and 35.5 months; and 41.5, 65, and
      49.5 months according to the three groups of monocyte counts. The relative risk
      of beginning the therapy was 1.62 (p<0.01) in patients with absolute monocyte
      count <0.25 G/l or >0.75 G/l, as compared to those with 0.25-0.75 G/l, and the
      risk of overal survival was 2.41 (p<0.01) in patients with absolute monocyte
      count lower than 0.25 G/l as compared to those with higher than 0.25 G/l. The
      relative risks remained significant in Rai 0 patients, too. The leading causes of
      mortality were infections (41.7%) and the chronic lymphocytic leukaemia (58.3%)
      in patients with low monocyte count, while tumours (25.9-35.3%) and other events
      (48.1 and 11.8%) occurred in patients with medium or high monocyte counts.
      CONCLUSIONS: Patients with low and high monocyte counts had a shorter time to
      treatment compared to patients who belonged to the intermediate monocyte count
      group. The low absolute monocyte count was associated with increased mortality
      caused by infectious complications and chronic lymphocytic leukaemia. The
      absolute monocyte count may give additional prognostic information in Rai stage
      0, too.

PMID- 25845319
TI  - [Reckoning: Assessment of 21 years' work in spinal surgery].
AB  - INTRODUCTION: Of the world-wide used Cotrel-Dubousset instrumentation and
      surgical technique providing breakthrough for the three-dimensional correction
      and multi-segmental fixation of spinal deformity surgery in Hungary is linked to
      the author's name, who carried out 1655 spine deformity surgeries in the last 21
      years. AIM: The aim of the author was to discuss his own results in the field of
      spine surgery and compare his own data to those published in the international
      literature. METHOD: At the beginning hooks, followed by hybrid instrumentation
      with hooks in thoracic area and transpedicular screws in lumbar spine have been
      used for the segmental fixation. During the correction process, initially the
      classic derotation maneuver was used, followed by the translation and then the in
      situ bending techniques and, finally, a combination of the above three techniques
      have been applied. RESULTS: In addition to the restoration of normal sagittal
      balance, an average of 40.8 degrees  (SD, 25.9), a 65.5% correction was achieved
      in the frontal plane, which partly exceeds and partly consistent with the
      published international results. The incidence of inflammation (3.9%), and
      mechanical complications (1.7%) was similar to the international average, while
      the incidence of neurological complications (0.48%) was slightly lower than the
      average of international data. CONCLUSIONS: The author believes that the better
      correction results as compared to the international average could be due to the
      always consistent application of the Cotrel-Dubousset instrumentation correction
      philosophy based on the meticulous segmental analysis of spine deformities.

PMID- 25845320
TI  - [Role of implantable loop recorder in the clinical diagnosis of syncope: results
      of the introduction of an effective diagnostic tool].
AB  - INTRODUCTION: Extension of electrocardiographic monitoring via loop recorder
      implantation may increase the diagnostic yield of syncope work-up. AIM: In this
      retrospective observational study, the authors wanted to evaluate the diagnostic
      performance of implantable loop recorder in the everyday clinical practice.
      METHOD: The authors analyzed the electronically stored data of all patients who
      underwent loop recorder implantation between 2005 and 2014 in their cardiology
      department because of recurrent syncope of undetermined origin. RESULTS: There
      were 52 loop recorder implantations within the study period. During the 167 (+/-
      136) days of monitoring, 36 (69.2%) diagnostic events occurred. In two-thirds of
      events, (46.2% of all monitored patients) a specific arrhythmia diagnosis was
      reached, allowing definitive treatment in these cases. In this selected
      population, there was no correlation between age, presence of known high-risk
      predictors, or accompanying trauma, and the mechanism of syncope. CONCLUSIONS:
      The high diagnostic rate of implantable loop recorder in the everyday clinical
      practice is in accordance with the findings in prospective clinical studies. This
      observation supports the early application of loop recorder in the diagnostic
      algorithm of syncope.

PMID- 25845321
TI  - [Symptomatology and treatment of persistent genital arousal disorder. Case
      report].
AB  - Persistent genital arousal disorder is a rare condition among women characterized
      by unwanted and intrusive sexual arousal that can persist for an extended period
      of time and unrelated to sexual desire or sexual stimuli. Since its first
      documentation in 2001, numerous studies have been dedicated to investigate its
      specifics. The persistent genital arousal occurs in the absence of sexual
      interest and fantasies and it causes excessive psychological suffering.
      Masturbation, spontaneous orgasm or sexual intercourse can offer only a temporary
      relief. Researches provide a limited insight into the characteristics of
      persistent genital arousal disorder. This paper presents a case and summarizes
      the scientific findings on prevalence, etiology and treatment perspectives.

PMID- 25845323
TI  - Aging population in Asia: Are we preparing ourselves enough?

PMID- 25845324
TI  - Risk factors of suicidal ideation among adolescents after Wenchuan earthquake in
      China.
AB  - BACKGROUND: Suicidal ideation is a common phenomenon in survivors after disaster
      event. AIM: To identify the change of suicidal ideation, and to test hypotheses
      concerning the suicidal ideation, depression and PTSD symptoms among adolescent
      survivors after the 2008 Wenchuan earthquake in China. METHODS: The suicidal
      ideation among high school students at 6, 12 and 18 months after the Wenchuan
      earthquake were investigated. Subjects included 737 student survivors in an
      affected high school. The PTSD Checklist-Civilian Version (PCL-C) and the Chinese
      Beck Depression Inventory (C-BDI) were used to measure the symptoms of PTSD and
      depression. RESULTS: The rates of suicidal ideation among the adolescent
      survivors at 6-, 12- and 18-month after the earthquake were 35.6%, 35.6% and
      30.7% respectively. Depression symptoms in the 18-month follow-up, suicidal
      ideations at 6 and 12 months after the earthquake were the independent risk
      factors of suicidal ideation in the 18-month follow-up. Depression symptoms were
      the strongest predictor of suicidal ideation after earthquake. CONCLUSION: An
      increased rate of suicidal ideation after the earthquake may be mainly due to
      depression but not to PTSD symptoms. The disaster-related psychological sequelae
      and the risk factors of suicidal ideation, especially depression symptoms, should
      be considered in the mental health services and suicide prevention.

PMID- 25845325
TI  - Psychiatry and the great wall of China.

PMID- 25845326
TI  - Quercetin-3-O-(2"-galloyl)-alpha-L-rhamnopyranoside attenuates cholesterol
      oxidation product-induced apoptosis by suppressing NF-kappaB-mediated cell death
      process in differentiated PC12 cells.
AB  - Cholesterol oxidation products are suggested to be involved in neuronal cell
      degeneration. We examined the preventive effect of quercetin-3-O-(2"-galloyl)
      alpha-L-rhamnopyranoside (QGR), a quercetin derivative, on the cholesterol
      oxidation product-induced neuronal cell death using differentiated PC12 cells in
      relation to nuclear factor (NF)-kappaB-mediated apoptotic process. 7
      Ketocholesterol and 25-hydroxycholesterol induced a decrease in the levels of BH3
      interacting-domain death agonist (Bid) and B cell lymphoma 2 (Bcl-2), increase in
      the levels of Bcl-2-associated X protein (Bax) and p53, loss of the mitochondrial
      transmembrane potential, cytochrome c release, activation of caspases, and
      cleavage of poly(ADP-ribose) polymerase 1 (PARP-1). 7-Ketocholesterol induced
      increase in cytosolic and nuclear NF-kappaB p65, nuclear phospho-NF-kappaB p65,
      cytosolic NF-kappaB p50, and cytosolic phospho-IkappaB-alpha levels. The addition
      of QGR, N-acetyl cysteine, or Bay 11-7085 attenuated the cholesterol oxidation
      product-induced changes in the apoptosis-related protein levels, activation of NF
      kappaB, formation of reactive oxygen species, depletion of glutathione (GSH),
      nuclear damage, and cell death. The results show that QGR may attenuate the
      cholesterol oxidation product-induced apoptosis in PC12 cells by suppressing the
      activation of the mitochondrial pathway and the caspase-8- and Bid-dependent
      pathways that is mediated by NF-kappaB activation. The preventive effect appears
      to be associated with the inhibitory effect on the formation of reactive oxygen
      species and depletion of GSH. 

PMID- 25845327
TI  - Assessment of modulated cytostatic drug resistance by automated gammaH2AX
      analysis.
AB  - The efficacy of many chemotherapeutic agents relies on the preferential
      destruction of rapidly dividing cancer cells by inducing various kinds of DNA
      damage. The most deleterious type of DNA lesions are DNA double-strand breaks
      (DSB), which can be detected by immunofluorescence staining of phosphorylated
      histone protein H2AX (gammaH2AX). Furthermore, gammaH2AX has been suggested as
      clinical pharmacodynamic biomarker in chemotherapeutic cancer treatment. A great
      challenge in treating neoplastic diseases is the varying response behavior among
      cancer patients. Thus, intrinsic or drug-induced overexpression of efflux pumps
      often leads to multiple drug resistance (MDR) and treatment failure. In
      particular, inter-individual differences in expression levels of efflux pumps,
      such as the permeability glycoprotein (P-gp), were shown to correlate with cancer
      progression. Several efficient cytostatic drugs, including the DSB-inducing agent
      etoposide (ETP) are known P-gp substrates. In this respect, modulation of MDR by
      P-gp inhibitors, like the immunosuppressives cyclosporine A (CsA) and rapamycin
      (Rapa) have been described. Here, we investigated the application of gammaH2AX
      focus assay to monitor the impact of CsA and Rapa on ETP-induced cytotoxicity in
      human peripheral blood mononuclear cells. Evaluation of gammaH2AX foci was
      performed by the automated fluorescence microscopy and interpretation system
      AKLIDES. Compared to ETP treatment alone, our results revealed a significant rise
      in gammaH2AX focus number and percentage of DSB-positive cells after cells have
      been treated with ETP in the presence of either CsA or Rapa. In contrast, DSB
      levels of cells incubated with CsA or Rapa alone were comparable to focus number
      of untreated cells. Our results successfully demonstrated how automated gammaH2AX
      analysis can be used as fast and reliable approach to monitor drug resistance and
      the impact of MDR modulators during treatment with DSB-inducing cytostatics..

PMID- 25845328
TI  - Site-specific immunochemical methylation assessment from genome DNA utilizing a
      conformational difference between looped-out target and stacked-in nontarget
      methylcytosines.
AB  - We report the sequence-selective immunochemical discrimination of methylcytosine
      from genomic DNA that we achieved by utilizing selective antibody binding to a
      looped-out methylcytosine in a bulge region and without using bisulfite
      treatment, a methylation-sensitive restriction enzyme, or PCR. First, we
      investigated the affinity of an anti-methylcytosine antibody for methylcytosine
      in full match, bulge, mismatch and abasic sites using surface plasmon resonance
      measurement and a microtiter plate to explore the differences as regards antibody
      binding to the target methylcytosine. The highest affinity, which was comparable
      to that in a single strand of DNA, was observed in the bulge region. In
      particular, no affinity was observed in a full match site. This is because there
      is no interaction such as hydrogen bond or pi-pi stacking for the bulged
      methylcytosine, thus enabling only the target in the bulge to be looped out.
      Methylated and unmethylated genomic DNA were blended to form a model DNA with
      which to assess the methylation ratio at a specific site. Fragmented DNA was
      hybridized with a biotinylated probe DNA, which has a sequence capable of forming
      a single base bulge at the target. The probe design is simple because it consists
      solely of the elimination of guanine paired with the target cytosine from a full
      match sequence. As a result, we successfully obtained a linear relationship
      (r(2)=0.9962) between the immunoassay signal and the methylation ratio of a
      specific site within 4 h.

PMID- 25845329
TI  - Up-conversion fluorescence "off-on" switch based on heterogeneous core-satellite
      assembly for thrombin detection.
AB  - NaGdF4: Yb, Er nanoparticles, with up-conversion (UC) fluorescence, were used for
      the first time to build an "off-on" switch based on Au core-UC satellites for
      thrombin detection. We fabricated the fluorescence sensor using thrombin aptamer
      modified Au core and complementary sequence modified UC satellites in liquid
      phase. With optimized assembled conditions, the yield of Au core-UC satellites
      achieved 80%. The fluorescence of UC nanoparticles quenched when satellite NP
      attached to Au core NP. Thrombin aptamer on the surface of Au core would bind to
      targets when thrombin existed in the system, then UC satellites were released and
      the quenched fluorescence recovered. The sensor showed high specificity for
      thrombin compared with other biomolecules and the limit of detection reached 3.5
      fg/mL. Application of this sensor to detect targets in human serum also achieved
      satisfactory results. The purpose of this work was to build an ultrasensitive
      sensor based on Au core-UC satellites for thrombin detection in human serum to
      achieve diagnosis of diseases.

PMID- 25845330
TI  - Ultrasensitive electrochemical immunosensor based on orderly oriented conductive
      wires for the detection of human monocyte chemotactic protein-1 in serum.
AB  - For the first time, a simple, ultrasensitive and label-free electrochemical
      monocyte chemotactic protein-1 (MCP-1) immunosensor based on orderly oriented
      conductive wires has been developed. A conductive wire, which is similar to an
      electron-conducting tunnel, was designed with Au nanoparticles (AuNPs) joined to
      Au@Pt core-shell microspheres via a cysteamine (CA) crosslinker. To enhance the
      sensitivity of the immunosensor, Au nanoparticles were electrodeposited onto the
      gold electrode, and CA was self-assembled via strong Au-S covalent bonds,
      providing an appropriate surface and promoting electron transfer. Next, Au@Pt
      core-shell microspheres with large surface area were grafted onto the modified
      electrode to immobilize more MCP-1 antibodies. MCP-1 is an initiating factor and
      biomarker of atherosclerotic diseases. Under optimal experimental conditions,
      differential pulse voltammetry (DPV) current changes were used to detect MCP-1
      with a broad linear range of 0.09-360 pg mL(-1) and a low detection limit of 0.03
      pg mL(-1) (S/N=3). The proposed immunosensor exhibited good selectivity,
      reproducibility and reusability. When applied to spiked serum samples, the data
      for the developed immunosensor were in agreement with an enzyme linked
      immunosorbent assay, suggesting that the electrochemical immunosensor would be
      suitable for practical detection.

PMID- 25845331
TI  - Label-free electrochemical aptasensor for femtomolar detection of 17beta
      estradiol.
AB  - We report an electrochemical aptasensor for the rapid, label-free detection of
      17beta-estradiol (E2) from femtomolar to micromolar levels. The sensor features
      an aptamer-functionalised nanoporous conducting polymer electrode whose surface
      potential is probed via electrochemical impedance spectroscopy. The unprecedented
      detection limit for E2 is explained via the redistribution of negative charges in
      the electrode double-layer region when the aptamer adopts a folded conformation
      around the small neutral target molecule. The sensor responds approximately
      logarithmically over a wide dynamic range of E2 concentration that spans
      biological trigger levels, with excellent discrimination against structurally
      similar molecules including progesterone, and robust operation in human urine.
      The generality of the approach of using conformationally gated small molecule
      binding aptamers is highlighted with a further example of adenosine detection via
      the adenosine binding aptamer. 

PMID- 25845332
TI  - Enzyme-guided plasmonic biosensor based on dual-functional nanohybrid for
      sensitive detection of thrombin.
AB  - Rapid and sensitive methodologies for the detection of protein are in urgent
      requirement for clinic diagnostics. Localized surface plasmon resonance (LSPR) of
      metal nanostructures has the potential to circumvent this problem due to its
      sensitive optical properties and strong electromagnetic near-field enhancements.
      In this work, an enzyme mediated plasmonic biosensor on the basis of a dual
      functional nanohybrid was developed for the detection of thrombin. By utilizing
      LSPR-responsive nanohybrid and anaptamer-enzyme conjugated reporting probe, the
      sensing platform brings enhanced signal, stability as well as simplicity.
      Enzymatic reaction catalyzed the reduction of Au(3+) to Au degrees  in situ,
      further leading to the rapid crystal growth of gold nanoparticles (AuNPs). The
      LSPR absorbance band and color changed company with the nanoparticle generation,
      which can be real-time monitoring by UV-visible spectrophotometer and naked eye.
      Nanohybrid constructed by gold and magnetic nanoparticles acts as a dual
      functional plasmonic unit, which not only plays the role of signal production,
      but also endows the sensor with the function of magnetic separation.
      Simultaneously, the introduction of enzyme effectively regulates the programming
      crystal growth of AuNPs. In addition, enzyme also serves as signal amplifier
      owing to its high catalysis efficiency. The response of the plasmonic sensor
      varies linearly with the logarithmic thrombin concentration up to 10nM with a
      limit of detection of 200 pM. The as-proposed strategy shows good analytical
      performance for thrombin determination. This simple, disposable method is
      promising in developing universal platforms for protein monitoring, drug
      discovery and point-of-care diagnostics.

PMID- 25845333
TI  - Development of glucose biosensors based on nanostructured graphene-conducting
      polyaniline composite.
AB  - A biosensor was fabricated by immobilizing glucose oxidase (GOD) into
      nanostructured graphene (GRA)-conducting polyaniline (PANI) nanocomposite, which
      was based on electrochemical polymerization of aniline in GRA synthesized by
      using electrochemical expansion of graphite in propylene carbonate electrolyte.
      Scanning electron spectroscopy (SEM), cyclic voltammetry (CV) and electrochemical
      impedance spectroscopy (EIS) were used to characterize the morphology and
      performance of the as-prepared biosensor, respectively. Amperometric measurements
      were carried out to optimize test conditions (pH and applied potential) of the
      biosensor. Under the optimal conditions, the biosensor showed a linear range from
      10.0 MUM to 1.48 mM (R(2)=0.9988) with a sensitivity of 22.1 MUA mM(-1) cm(-2),
      and a detection limit of 2.769 MUM (S/N=3). The apparent Michaelis-Menten
      constant (KM(a)) was estimated to be 3.26 mM. The interference from glycine
      (Gly), D-galactose (D-Gal), urea (Urea), L-phenylalanine (L-Phe), ascorbic acid
      (AA), and L-tyrosine (L-Tyr) was also investigated. The results indicated that
      the biosensor exhibit high sensitivity and superior selectivity, providing a
      hopeful candidate for glucose biosensing.

PMID- 25845334
TI  - Ultrasensitive detection of drug resistant cancer cells in biological matrixes
      using an amperometric nanobiosensor.
AB  - Multidrug resistance (MDR) is a key issue in the failure of cancer chemotherapy
      and its detection will be helpful to develop suitable therapeutic strategies for
      cancer patients and overcome the death rates. In this direction, we designed a
      new amperometric sensor (a medical device prototype) to detect drug resistant
      cancer cells by sensing "Permeability glycoprotein (P-gp)". The sensor probe is
      fabricated by immobilizing monoclonal P-gp antibody on the gold nanoparticles
      (AuNPs) conducting polymer composite. The detection relies on a sandwich-type
      approach using a bioconjugate, where the aminophenyl boronic acid (APBA) served
      as a recognition molecule which binds with the cell surface glycans and hydrazine
      (Hyd) served as an electrocatalyst for the reduction of H2O2 which are attached
      on multi-wall carbon nanotube (MWCNT) (APBA-MWCNT-Hyd). A linear range for the
      cancer cell detection is obtained between 50 and 100,000 cells/mL with the
      detection limit of 23+/-2 cells/mL. The proposed immunosensor is successfully
      applied to detect MDR cancer cells (MDRCC) in serum and mixed cell samples.
      Interferences by drug sensitive (SKBr-3 and HeLa), noncancerous cells (HEK-293
      and OSE), and other chemical molecules present in the real sample matrix are
      examined. The sensitivity of the proposed immunosensor is excellent compared with
      the conventional reporter antibody based assay.

PMID- 25845335
TI  - Microfluidics and nanoparticles based amperometric biosensor for the detection of
      cyanobacteria (Planktothrix agardhii NIVA-CYA 116) DNA.
AB  - Some of the cyanobacteria produce protease inhibitor oligopeptides such as
      cyanopeptolins and cause drinking water contamination; hence, their detection has
      great importance to monitor the well-being of water sources that is used for
      human consumption. In the current study, a fast and sensitive nucleic acid
      biosensor assay has been described where cyanopeptolin coding region of one of
      the cyanobacteria (Planktothrix agardhii NIVA-CYA 116) genome has been used as
      target for monitoring of the fresh water resources. A biochip that has two sets
      of Au electrode arrays, each consist of shared reference/counter electrodes and 3
      working electrodes has been used for the assay. The biochip has been integrated
      to a microfluidics system and all steps of the assay have been performed during
      the reagent flow to achieve fast and sensitive DNA detection. On-line
      hybridization of the target on to the capture probe immobilized surface resulted
      in a very short assay duration with respect to the conventional static assays.
      The binding of the avidin and enzyme modified Au nanoparticles to the
      biotinylated detection probe and the subsequent injection of the substrate
      enabled a real-time amperometric measurement with a detection limit of 6*10(-12)
      M target DNA (calibration curve r(2)=0.98). The developed assay enables fast and
      sensitive detection of cyanopeptolin producing cyanobacteria from freshwater
      samples and hence shows a promising technology for toxic microorganism detection
      from environmental samples.

PMID- 25845336
TI  - Detection of methicillin-resistant staphylococci by biosensor assay consisting of
      nanoscale films on optical fiber long-period gratings.
AB  - Methicillin-resistance among Staphylococcus species is a major health problem in
      hospitals, communities, and animals. There is a need for culture-free diagnostic
      assays that can be carried out rapidly, and maintain a high degree of sensitivity
      and specificity. To address this need an ionic self-assembled multilayer (ISAM)
      film was deposited on the surface of a long-period grating (LPG) optical fiber by
      immersion alternately in poly-allylamine hydrochloride and in poly-1-[p-(3'
      carboxy-4'-hydroxyphenylazo) benzenesulfonamido]-1,2-ethandiyl (PCBS), resulting
      in terminal carboxyl groups on the LPG-ISAM. The terminal carboxyl groups were
      covalently conjugated to monoclonal antibodies (MAb) specific to penicillin
      binding-protein 2a of methicillin resistant (MR) staphylococci. After exposure of
      the LPG-ISAM to 10(2) colony forming units (CFU)/ml of MR S. aureus (MRSA) for 50
      min., light transmission was reduced by 19.7%. In contrast, after exposure to
      10(6) CFU/ml of methicillin-sensitive S. aureus (MSSA) attenuation of light
      transmission was less than 1.8%. Exposure of the LPG-ISAM to extracts of liver,
      lungs, or spleen from mice infected with MRSA attenuated light transmission by
      11.7-73.5%. In contrast, exposure of the biosensor to extracts from MSSA-infected
      mice resulted in 5.6% or less attenuation of light transmission. When the sensor
      was tested with 36 strains of MR staphylococci, 15 strains of methicillin
      sensitive staphylococci, 10 strains of heterologous genera (all at 10(4) CFU/ml),
      or tissue samples from mice infected with MRSA, there was complete agreement
      between MR and non-MR bacteria determined by antibiotic susceptibility testing
      and the biosensor assay when the cutoff value for attenuation of light
      transmission was 6.3%. Thus, the biosensor described has the potential to detect
      MR staphylococci in clinical samples with a high degree of sensitivity and
      specificity.

PMID- 25845337
TI  - Polypyrrole encapsulation on flower-like porous NiO for advanced high-performance
      supercapacitors.
AB  - Polypyrrole (PPy) encapsulated 3D flower-like NiO was prepared to investigate the
      role of PPy coating for high-performance electrodes. NiO@PPy showed a better
      electrochemical performance than pure NiO, and a "trade-off effect" between
      electrical conductivity and ion diffusion resistance was observed with different
      PPy coating thickness. 

PMID- 25845338
TI  - Per- and polyfluoroalkyl substances in materials, humans and the environment.

PMID- 25845340
TI  - Simultaneous silencing of beta-catenin and signal transducer and activator of
      transcription 3 synergistically induces apoptosis and inhibits cell proliferation
      in HepG2 liver cancer cells.
AB  - The tumorigenesis and maintenance of a cancer cells is dependent upon the
      collaboration of multiple signaling pathways. Signal transducer and activator of
      transcription 3 (STAT3) and beta-catenin are at the center of multiple cancer
      associated signaling pathways; therefore, simultaneously targeting STAT3 and beta
      catenin may be a potential cancer treatment, leading to induced lethality of
      cancer cells. In the present study, HepG2 liver cancer cells were transfected
      with small interfering RNA (siRNA) against beta-catenin and STAT3 alone or in
      combination. The cell growth was assessed using an MTT assay and the levels of
      cell apoptosis were detected using flow cytometry. Protein levels of caspase-3,
      cleaved caspase-3, poly(ADP-ribose) polymerase (PARP) and cleaved PARP were
      determined using western blot analysis. Following siRNA transfection, beta
      catenin and STAT3 protein levels decreased at 72 h. HepG2 cell growth inhibition
      and early apoptosis in the beta-catenin and STAT3 siRNA co-transfection group
      were significantly greater than those in the groups transfected with beta-catenin
      or STAT3 siRNA alone. Decreased caspase-3 and PARP levels, as well as enhanced
      cleavage of caspase-3 and PARP were observed in the beta-catenin and STAT3 co
      transfection group. Simultaneous silencing of beta-catenin and STAT3 using siRNAs
      resulted in an enhanced loss of cell viability and induction of apoptosis in
      HepG2 liver cancer cells, suggesting that these genes are promising targets for
      the further preclinical and clinical development of anti-cancer therapeutic
      strategies, which target several cancer signaling pathways simultaneously.

PMID- 25845341
TI  - Organocatalytic asymmetric addition of naphthols and electron-rich phenols to
      isatin-derived ketimines: highly enantioselective construction of
      tetrasubstituted stereocenters.
AB  - A quinine-derived thiourea organocatalyst promoted the highly enantioselective
      addition of naphthols and activated phenols to ketimines derived from isatins.
      The reaction afforded chiral 3-amino-2-oxindoles with a quaternary stereocenter
      in high yields (up to 99%) with excellent enantioselectivity (up to 99% ee). To
      the best of our knowledge, this transformation is the first highly
      enantioselective addition of naphthols to ketimines.

PMID- 25845339
TI  - Impact of dietary components on NK and Treg cell function for cancer prevention.
AB  - An important characteristic of cancer is that the disease can overcome the
      surveillance of the immune system. A possible explanation for this resistance
      arises from the ability of tumor cells to block the tumoricidal activity of host
      immune cells such as natural killer (NK) cells by inducing the localized
      accumulation of regulatory T (Treg) cells. Evidence exists that components in
      commonly consumed foods including vitamins A, D, and E, water-soluble
      constituents of mushrooms, polyphenolics in fruits and vegetables, and n-3 fatty
      acids in fish oil can modulate NK cell activities, Treg cell properties, and the
      interactions between those two cell types. Thus, it is extremely important for
      cancer prevention to understand the involvement of dietary components with the
      early stage dynamics of interactions among these immune cells. This review
      addresses the potential significance of diet in supporting the function of NK
      cells, Treg cells, and the balance between those two cell types, which ultimately
      results in decreased cancer risk.

PMID- 25845342
TI  - Changes in the Temperament and Character Inventory dimensions after paroxetine
      treatment in patients with major depressive disorder.
AB  - Previous studies have reported changes in the dimensions of the Temperament and
      Character Inventory (TCI) after patients with major depressive disorder are
      treated. We aimed to investigate the changes in the TCI dimensions after
      paroxetine treatment in patients with major depressive disorder. Forty-eight
      patients were enrolled in this study and were treated with 10-40 mg/day of
      paroxetine for 6 weeks. The TCI was completed twice, at weeks 0 and 6. We used
      the Montgomery-Asberg Depression Rating Scale (MADRS) to evaluate patients. The
      participants were divided into three groups (responders, non-responders, and
      early responders) based on treatment response. The scores of each dimension of
      the TCI were compared before and after treatment using repeated-measures two-way
      analyses of variance. In the responders group (n = 24), no TCI dimension scores
      changed significantly during treatment, but the interaction between sex and MADRS
      score change was significantly associated with the results. In the non-responders
      group (n = 15), the self-directedness score increased significantly during the
      treatment period (p = 0.000), and the change in MADRS score significantly
      affected the results. In the early responders group (n = 9), no TCI dimension
      scores changed significantly during treatment. The results of the present study
      may reveal a possible correlation between paroxetine treatment and changes in
      personality traits.

PMID- 25845343
TI  - Phosphate and thiophosphate biphenyl analogs as steroid sulfatase inhibitors.
AB  - In the present work, we report convenient methods for the synthesis and
      biological evaluation of phosphate and thiophosphate biphenyl derivatives
      exhibiting steroid sulfatase (STS) activity. The described synthesis is based on
      straightforward preparation of biphenyl-4-ol and 4'-hydroxy-biphenyl-4-carboxylic
      acid ethyl ester modified with various phosphate or thiophosphate moieties. The
      inhibitory effects of these compounds were tested on STS isolated from human
      placenta and led to two compounds of interest, 5a and 5d with IC50 values of 28.0
      and 22.1 uM, respectively and that had interesting new binding modes in the STS
      active site.

PMID- 25845344
TI  - A rare case of a punched nerve syndrome of the deep motor branch of the ulnar
      nerve.
AB  - INTRODUCTION: Peripheral compression neuropathy of the ulnar nerve is a frequent
      condition, most likely encountered at the ulnar sulcus or the Guyon's canal. High
      resolution ultrasound (HRUS) can often identify the site of injury. Primarily
      idiopathic, compression neuropathy can stem from a punched nerve syndrome, in
      which direct contact between an arterial branch and the nerve leads to
      compression. MATERIALS AND METHODS: A 42-year-old male patient was examined by
      means of HRUS using a 17-5 MHz linear transducer on a Philips iU22((r)) (Philips,
      Bothell, Washington, USA). RESULTS: After reporting a punched nerve syndrome of
      the deep motor branch of the ulnar nerve distal to the Guyon's canal, the patient
      underwent surgery and showed electrophysiological and clinical improvement 6
      months after decompression. CONCLUSION: HRUS is a viable method to demonstrate a
      punched nerve syndrome. In conjunction with clinical presentation, even unlikely
      sites of compression such as the deep motor branch of the ulnar nerve can be
      identified.

PMID- 25845345
TI  - Non-syndromic hearing loss gene identification: A brief history and glimpse into
      the future.
AB  - From the first identified non-syndromic hearing loss gene in 1995, to those
      discovered in present day, the field of human genetics has witnessed an
      unparalleled revolution that includes the completion of the Human Genome Project
      in 2003 to the $1000 genome in 2014. This review highlights the classical and
      cutting-edge strategies for non-syndromic hearing loss gene identification that
      have been used throughout the twenty year history with a special emphasis on how
      the innovative breakthroughs in next generation sequencing technology have
      forever changed candidate gene approaches. The simplified approach afforded by
      next generation sequencing technology provides a second chance for the many
      linked loci in large and well characterized families that have been identified by
      linkage analysis but have presently failed to identify a causative gene. It also
      discusses some complexities that may restrict eventual candidate gene discovery
      and calls for novel approaches to answer some of the questions that make this
      simple Mendelian disorder so intriguing.

PMID- 25845346
TI  - Orchestrating the biosynthesis of an unnatural pyrrolysine amino Acid for its
      direct incorporation into proteins inside living cells.
AB  - We here report the construction of an E. coli expression system able to
      manufacture an unnatural amino acid by artificial biosynthesis. This can be
      orchestrated with incorporation into protein by amber stop codon suppression
      inside a living cell. In our case an alkyne-bearing pyrrolysine amino acid was
      biosynthesized and incorporated site-specifically allowing orthogonal double
      protein labeling. 

PMID- 25845347
TI  - OSM is overexpressed in knee osteoarthritis and Notch signaling is involved in
      the effects of OSM on MC3T3-E1 cell proliferation and differentiation.
AB  - Knee osteoarthritis (OA) is the most prevalent type of OA and the cytokine,
      oncostatin M (OSM), may contribute to the pathogenesis of OA. However, the exact
      role of OSM in the development of knee OA and the underlying mechanisms are not
      yet fully understood. This study was designed to detect the expression of OSM in
      the synovial tissue of patients with knee OA. Furthermore, we investigated
      whether Notch signaling is involved in the effects of OSM on MC3T3-E1 cell
      proliferation and differentiation. The synovial tissue of the knee joint was
      collected from 32 patients with knee OA. We detected OSM mRNA and protein
      expression (by RT-qPCR and western blot analysis, respectively) in the synovial
      tissue of the knee joint, and the expression level of OSM was higher in the
      patients with knee OA compared with the controls. MTT assay was used in the in
      vitro experiments to determine MC3T3-E1 cell proliferation, and cell
      differentiation was determined by measuring alkaline phosphatase (ALP) activity
      and osteocalcin (OCN) expression. The results from our in vitro experiments
      revealed that OSM induced bone formation by increasing osteoblast cell
      proliferation and differentiation. In addition, the expression levels of Notch
      ligand, receptor and target gene, including Delta-like 1 (Dll1), Notch homolog 1
      (Notch1) and Hes family bHLH transcription factor 1 (Hes1) were decreased
      following treatment with OSM in a time-dependent manner in the MC3T3-E1 cells. A
      Dll1 overexpression vector was transfected into the cells to activate Notch
      signaling, and the results revealed that the activation of Notch signaling
      attenuated the effects of OSM on MC3T3-E1 cell proliferation and differentiation.
      In conclusion, our data demonstrate that elevated levels of OSM in synovial
      tissue induce bone formation by increasing osteoblast cell proliferation and
      differentiation. The Notch signaling pathway was found to be one of the signaling
      pathways that inhibit OSM-induced MC3T3-E1 cell proliferation and
      differentiation. The findings of this study may broaden our understanding of the
      mechanisms behing the role of OSM in the development of knee OA.

PMID- 25845351
TI  - Plasma lipid analysis by hydrophilic interaction liquid chromatography coupled
      with electrospray ionization tandem mass spectrometry.
AB  - A novel method for the analysis of endogenous lipids and related compounds was
      developed employing hydrophilic interaction liquid chromatography with
      electrospray ionization tandem mass spectrometry. A hydrophilic interaction
      liquid chromatography with carbamoyl stationary phase achieved clear separation
      of phosphatidylcholine, lysophosphatidylcholine, sphingomyelin, ceramide, and
      mono-hexsosyl ceramide groups with good peak area repeatability (RSD% < 10) and
      linearity (R(2) > 0.99). The established method was applied to human plasma
      assays and a total of 117 endogenous lipids were successfully detected and
      reproducibly identified. In addition, we investigated the simultaneous detection
      of small polar metabolites such as amino and organic acids co-existing in the
      same biological samples processed in a single analytical run with lipids. Our
      results show that hydrophilic interaction liquid chromatography is a useful tool
      for human plasma lipidome analysis and offers more comprehensive metabolome
      coverage. 

PMID- 25845352
TI  - Do proton pump inhibitors contribute to weight gain?

PMID- 25845354
TI  - Trail following response of larval Cactoblastis cactorum to 2-acyl-1,3
      cyclohexanediones.
AB  - Caterpillars of Cactoblastis cactorum secrete onto the surface of host cactuses
      droplets of an oily fluid that issues from the orifices of their paired
      mandibular glands. The fluid contains a series of 2-acyl-1,3-cyclohexanediones
      that, collectively, have been shown to elicit trail-following behavior from the
      caterpillars. This study reports the results of bioassays to determine the
      ability of two specific compounds, previously shown to be prominent components of
      the mandibular glands of pyralid caterpillars, 4-hydroxy-2-oleoyl-1,3
      cyclohexanedione and 2-oleoyl-1,3-cyclohexanedione, to elicit trail-following
      behavior from the larvae of C. cactorum. Additionally bioassayed were structural
      fragments of these molecules. The relative effectiveness of the chemicals in
      eliciting trail following, the effect of varying concentration on the trail
      following response, the importance of specific functional groups to the trail
      following response, and the threshold sensitivity of the caterpillar to the
      pheromone were determined. The study showed that while all the tested compounds
      elicited some degree of trail following, they differed significantly in their
      effectiveness. The most effective of the compounds was 4-hydroxy-2-oleoyl-1,3
      cyclohexanedione, which, on a per unit volume basis, was as effective as whole
      gland extract. Caterpillars secreted large quantities of fluid from the glands,
      and the threshold response to 4-hydroxy-2-oleoyl-1,3-cyclohexanedione occurred at
      a relative high application rate compared to trail pheromones of other social
      caterpillars and eusocial insects. This and the observation that the trail marker
      is secreted from the mandibular glands suggests that the use of 2-acyl-1,3
      cyclohexanediones as trail markers is secondary, and that these compounds
      function primarily in some other, as yet undetermined, context.

PMID- 25845353
TI  - Preoperative Predictive Factors of Successful Weight Loss and Glycaemic Control 1
      Year After Gastric Bypass for Morbid Obesity.
AB  - BACKGROUND: Gastric bypass (GBP) is one of the most effective surgical procedures
      to treat morbid obesity and the related comorbidities. This study aimed at
      identifying preoperative predictors of successful weight loss and type 2 diabetes
      mellitus (T2DM) remission 1 year after GBP. METHODS: Prospective longitudinal
      study of 771 patients who underwent GBP was performed at four Italian centres
      between November 2011 and May 2013 with 1-year follow-up. Preoperative
      anthropometric, metabolic and social parameters, the surgical technique and the
      previous failed bariatric procedures were analyzed. Weight, the body mass index
      (BMI), the percentage of excess weight lost (% EWL), the percentage of excess BMI
      lost (% BMIL) and glycated haemoglobin (HbA1c) were recorded at follow-up.
      RESULTS: Univariate and multivariate analysis showed that BMI <50 kg/m(2) (p =
      0.006) and dyslipidaemia (p = 0.05) were predictive factors of successful weight
      loss. Multivariate analysis of surgical technique showed significant weight loss
      in patients with a small gastric pouch (p < 0.001); the lengths of alimentary and
      biliary loops showed no statistical significance. All diabetic patients had a
      significant reduction of HbA1c (p < 0.001) after surgery. BMI >= 50 kg/m(2) (p =
      0.02) and low level of preoperative HbA1c (p < 0.01) were independent risk
      factors of T2DM remission after surgery. CONCLUSIONS: This study provides a
      useful tool for making more accurate predictions of best results in terms of
      weight loss and metabolic improvement.

PMID- 25845355
TI  - Cadmium, copper, and lead accumulation and bioconcentration in the vegetative and
      reproductive organs of Raphanus sativus: implications for plant performance and
      pollination.
AB  - Several studies have found high levels of cadmium (Cd), copper (Cu), and lead
      (Pb) in honey bee hives located near urbanized or industrial areas. Insect
      herbivores and pollinators may come in contact with environmental contaminants in
      the leaves and flowers they forage upon in these areas. Our study quantified
      which of these metals are accumulated in the tissues of a common weedy plant that
      can serve as a route of exposure for insects. We grew Raphanus sativus (crop
      radish) in semi-hydroponic sand culture in the greenhouse. Plants were irrigated
      with nutrient solutions containing Cd, Cu, or Pb at four concentrations (control,
      low, medium, high). Plant performance, floral traits, and metal accumulation were
      measured in various vegetative and reproductive plant organs. Floral traits and
      flower number were unaffected by all metal treatments. Copper accumulated at the
      highest concentrations in flowers compared to the other two metals. Copper and Cd
      had the highest translocation indices, as well as higher bioconcentration factors
      compared to Pb, which was mostly immobile in the plant. Copper posed the highest
      risk due to its high mobility within the plant. In particular, accumulation of
      metals in leaves and flowers suggests that herbivores and pollinators visiting
      and foraging on these tissues may be exposed to these potentially toxic
      compounds.

PMID- 25845356
TI  - A membraneless air-breathing hydrogen biofuel cell based on direct wiring of
      thermostable enzymes on carbon nanotube electrodes.
AB  - A biocathode was designed by the modification of a carbon nanotube (CNT) gas
      diffusion electrode with bilirubin oxidase from Bacillus pumilus, achieving high
      current densities up to 3 mA cm(-2) for the reduction of O2 from air. A
      membraneless air-breathing hydrogen biofuel cell was designed by combination of
      this cathode with a functionalized CNT-based hydrogenase anode. 

PMID- 25845357
TI  - Hourly differences in air pollution on the risk of asthma exacerbation.
AB  - We investigated the association between hourly differences in air pollution and
      asthma exacerbation in Korea using asthma-related emergency department data and
      verified seasonality and demographic modifiers with an hourly temporal
      resolution. We applied time-stratified case-crossover adjusted for weather and
      influenza; the lag was stratified as 1-6, 7-12, 13-18, 19-24, 25-48, and 49-72 h.
      Odds ratios (95% confidence interval) per interquartile range increase were 1.05
      (1.00-1.11) after 1-6 h for PM10-2.5 and 1.10 (1.04-1.16) after 19-24 h for O3.
      Effect size was 1.14 (1.06-1.22) at a 1-6 h lag in spring for PM10-2.5, and 1.25
      (1.03-1.51) at a 25-48 h lag in winter for O3. O3 effects were age- and low socio
      economic status-modified at a 7-12 h lag [1.25 (1.04-1.51)]. Increased PM10-2.5
      and O3 increased the risk of asthma exacerbation; the effect of PM10-2.5 was most
      immediate.

PMID- 25845358
TI  - A biodynamic model predicting waterborne lead bioaccumulation in Gammarus pulex:
      Influence of water chemistry and in situ validation.
AB  - Metals bioaccumulated in aquatic organisms are considered to be a good indicator
      of bioavailable metal contamination levels in freshwaters. However,
      bioaccumulation depends on the metal, the species, and the water chemistry that
      influences metal bioavailability. In the laboratory, a kinetic model was used to
      describe waterborne Pb bioaccumulated in Gammarus pulex. Uptake and elimination
      rate constants were successfully determined and the effect of Ca(2+) on Pb uptake
      was integrated into the model. Thereafter, accumulated Pb concentrations in
      organisms were predicted with the model and compared with those measured in
      native populations from the Seine watershed (France). The predictions had a good
      agreement with the bioaccumulation levels observed in native gammarids and
      particularly when the effect of calcium was considered. To conclude, kinetic
      parameters experimentally derived for Pb in G. pulex are applicable in
      environmental conditions. Moreover, the consideration of the water's chemistry is
      crucial for a reliable interpretation of bioaccumulation. 

PMID- 25845359
TI  - Synthetic promoters consisting of defined cis-acting elements link multiple
      signaling pathways to probenazole-inducible system.
AB  - Probenazole (3-allyloxy-1,2-benzisothiazole-1,1-dioxide, PBZ), the active
      component of Oryzemate, could induce systemic acquired resistance (SAR) in plants
      through the induction of salicylic acid (SA) biosynthesis. As a widely used
      chemical inducer, PBZ is a good prospect for establishing a new chemical
      inducible system. We first designed artificially synthetic promoters with tandem
      copies of a single type of cis-element (SARE, JERE, GCC, GST1, HSRE, and W-box)
      that could mediate the expression of the beta-glucuronidase (GUS) reporter gene
      in plants upon PBZ treatment. Then we combined different types of elements in
      order to improve inducibility in the PBZ-inducible system. On the other hand, we
      were surprised to find that the cis-elements, which are responsive to jasmonic
      acid (JA) and ethylene, also responded to PBZ, implying that SA, JA, and ethylene
      pathways also would play important roles in PBZ's action. Further analysis
      demonstrated that PBZ also induced early events of innate immunity via a
      signaling pathway in which Ca(2+) influx and mitogen-activated protein kinase
      (MAPK) activity were involved. We constructed synthesized artificial promoters to
      establish a PBZ chemical-inducible system, and preliminarily explored SA, JA,
      ethylene, calcium, and MAPK signaling pathways via PBZ-inducible system, which
      could provide an insight for in-depth study. 

PMID- 25845360
TI  - Alternaria toxin-induced resistance in rose plants against rose aphid
      (Macrosiphum rosivorum): effect of tenuazonic acid.
AB  - Many different types of toxins are produced by the fungus, Alternaria alternata
      (Fr.) Keissler. Little is known, however, regarding the influence of these toxins
      on insects. In this study, we investigated the toxin-induced inhibitory effects
      of the toxin produced by A. alternata on the rose aphid, Macrosiphum rosivorum,
      when the toxin was applied to leaves of the rose, Rosa chinensis. The results
      demonstrated that the purified crude toxin was non-harmful to rose plants and
      rose aphids, but had an intensive inhibitory effect on the multiplication of
      aphids. The inhibitory index against rose aphids reached 87.99% when rose plants
      were sprayed with the toxin solution at a low concentration. Further results from
      bioassays with aphids and high performance liquid chromatography (HPLC) analyses
      demonstrated that tenuazonic acid (TeA) was one of the most important resistance
      related active components in the crude toxin. The content of TeA was 0.1199% in
      the crude toxin under the HPLC method. Similar to the crude toxin, the inhibitory
      index of pure TeA reached 83.60% 15 d after the rose plants were sprayed with
      pure TeA solution at the lower concentration of 0.060 MUg/ml, while the contents
      of residual TeA on the surface and in the inner portion of the rose plants were
      only 0.04 and 0.00 ng/g fresh weight of TeA-treated rose twigs, respectively, 7 d
      after the treatment. Our results show that TeA, an active component in the A.
      alternata toxin, can induce the indirect plant-mediated responses in rose plants
      to intensively enhance the plant's resistances against rose aphids, and the
      results are very helpful to understand the plant-mediated interaction between
      fungi and insects on their shared host plants. 

PMID- 25845361
TI  - Evaluation of yeasts from Tibetan fermented products as agents for biocontrol of
      blue mold of Nashi pear fruits.
AB  - A total of 20 strains of yeast isolated from Tibetan fermented products were
      screened for antagonism against blue mold of pear caused by Penicillium expansum.
      Six isolates that inhibited incidence of postharvest decay by 35% or more were
      selected for further screening. Among them, the most effective was Rhodotorula
      mucilaginosa. The results showed that washed cell suspensions of R. mucilaginosa
      yielded better antagonistic efficacy than unwashed cell-culture mixtures, cell
      free culture filtrates, and autoclaved cell cultures. Biocontrol activity
      improved with increasing concentrations of incubated cells. The best
      concentration was 1*10(8) cells/ml, at which the incidence of decay was only
      16.7% after 6 d of incubation. The germination of conidia of P. expansum in vitro
      was significantly inhibited by both washed cell-suspensions and unwashed cell
      culture mixtures. Rapid colonization by yeast at different concentrations showed
      a relationship between yeast-cell concentration and biocontrol activity. Although
      the titratable acidity of pear fruits increased after treatment, R. mucilaginosa
      did not affect the total soluble solids or ascorbic acid content. This is the
      first study to report that the yeast R. mucilaginosa from Tibet Autonomous Region
      of China may have potential as an antagonist to control the postharvest decay of
      pear fruits. 

PMID- 25845362
TI  - Mutation breeding of high 4-androstene-3,17-dione-producing Mycobacterium
      neoaurum ZADF-4 by atmospheric and room temperature plasma treatment.
AB  - Steroid medication is used extensively in clinical applications and comprises a
      large and vital part of the pharmaceutical industry. However, the difficulty of
      separating 4-androstene-3,17-dione (AD) from 1,4-androstadiene-3,17-dione (ADD)
      restricts the application of the microbial transformation of phytosterols in the
      industry. A novel atmospheric and room temperature plasma (ARTP) treatment, which
      employs helium as the working gas, was used to generate Mycobacterium neoaurum
      mutants producing large amounts of AD. After treatment of cultures with ARTP,
      four mutants were selected using a novel screening method with a color assay.
      Among the mutants, M. neoaurum ZADF-4 was considered the best candidate for
      industrial application. When the fermentation medium contained 15 g/L
      phytosterols and was cultivated on a rotary shaker at 160 r/min at 30  degrees C
      for 7 d, (6.28+/-0.11) g/L of AD and (0.82+/-0.05) g/L of ADD were produced by
      the ZADF-4 mutant, compared with (4.83+/-0.13) g/L of AD and (2.34+/-0.06) g/L of
      ADD by the original strain, M. neoaurum ZAD. Compared with ZAD, the molar yield
      of AD increased from 48.3% to 60.3% in the ZADF-4 mutant. This result indicates
      that ZADF-4 may have potential for industrial production of AD. 

PMID- 25845363
TI  - Expression profiles of miRNAs in Gossypium raimondii.
AB  - miRNAs are a class of conserved, small, endogenous, and non-protein-coding RNA
      molecules with 20-24 nucleotides (nt) in length that function as post
      transcriptional modulators of gene expression in eukaryotic cells. Functional
      studies have demonstrated that plant miRNAs are involved in the regulation of a
      wide range of plant developmental processes. To date, however, no research has
      been carried out to study the expression profiles of miRNAs in Gossypium
      raimondii, a model cotton species. We selected 16 miRNAs to profile their tissue
      specific expression patterns in G. raimondii four different tissues, and these
      miRNAs are reported to play important roles in plant growth and development. Our
      results showed that the expression levels of these miRNAs varied significantly
      from one to another in a tissue-dependent manner. Eight miRNAs, including miR
      159, miR-162, miR-164, miR-172, miR-390, miR-395, miR-397, and miR-398, exhibited
      exclusively high expression levels in flower buds, suggesting that these miRNAs
      may play significant roles in floral development. The expression level of miR-164
      was relatively high in shoots beside flower buds, implying that the function of
      miR-164 is not only limited to floral development but it may also play an
      important role in shoot development. Certain miRNAs such as miR-166 and miR-160
      were extremely highly expressed in all of the four tissues tested compared with
      other miRNAs investigated, suggesting that they may play regulatory roles at
      multiple development stages. This study will contribute to future studies on the
      functional characterization of miRNAs in cotton. 

PMID- 25845364
TI  - Cassava stillage and its anaerobic fermentation liquid as external carbon sources
      in biological nutrient removal.
AB  - The aim of this study was to investigate the effects of one kind of food industry
      effluent, cassava stillage and its anaerobic fermentation liquid, on biological
      nutrient removal (BNR) from municipal wastewater in anaerobic-anoxic-aerobic
      sequencing batch reactors (SBRs). Experiments were carried out with cassava
      stillage supernatant and its anaerobic fermentation liquid, and one pure compound
      (sodium acetate) served as an external carbon source. Cyclic studies indicated
      that the cassava by-products not only affected the transformation of nitrogen,
      phosphorus, poly-beta-hydroxyalkanoates (PHAs), and glycogen in the BNR process,
      but also resulted in higher removal efficiencies for phosphorus and nitrogen
      compared with sodium acetate. Furthermore, assays for phosphorus accumulating
      organisms (PAOs) and denitrifying phosphorus accumulating organisms (DPAOs)
      demonstrated that the proportion of DPAOs to PAOs reached 62.6% (Day 86) and
      61.8% (Day 65) when using cassava stillage and its anaerobic fermentation liquid,
      respectively, as the external carbon source. In addition, the nitrate utilization
      rates (NURs) of the cassava by-products were in the range of 5.49-5.99 g N/(kg
      MLVSS?h) (MLVSS is mixed liquor volatile suspended solids) and 6.63-6.81 g N/(kg
      MLVSS?h), respectively. The improvement in BNR performance and the reduction in
      the amount of cassava stillage to be treated in-situ make cassava stillage and
      its anaerobic fermentation liquid attractive alternatives to sodium acetate as
      external carbon sources for BNR processes. 

PMID- 25845365
TI  - Effect of culturing conditions on the expression of key enzymes in the
      proteolytic system of Lactobacillus bulgaricus.
AB  - The proteolytic system of Lactobacillus bulgaricus breaks down milk proteins into
      peptides and amino acids, which are essential for the growth of the bacteria. The
      aim of this study was to determine the expressions of seven key genes in the
      proteolytic system under different culturing conditions (different phases,
      initial pH values, temperatures, and nitrogen sources) using real-time polymerase
      chain reaction (RT-PCR). The transcriptions of the seven genes were reduced by 30
      fold on average in the stationary phase compared with the exponential growth
      phase. The transcriptions of the seven genes were reduced by 62.5-, 15.0-, and
      59.0-fold in the strains KLDS 08006, KLDS 08007, and KLDS 08012, respectively,
      indicating that the expressions of the seven genes were significantly different
      among strains. In addition, the expressions of the seven genes were repressed in
      the MRS medium containing casein peptone. The effect of peptone supply on PepX
      transcription was the weakest compared with the other six genes, and the impact
      on OppD transcription was the strongest. Moreover, the expressions of the seven
      genes were significantly different among different strains (P<0.05). All these
      results indicated that the culturing conditions affected the expression of the
      proteolytic system genes in Lactobacillus bulgaricus at the transcription level. 

PMID- 25845366
TI  - Transcatheter aortic valve implantation for Chinese patients with bicuspid aortic
      valve.

PMID- 25845367
TI  - Looking for protein stabilizing drugs with thermal shift assay.
AB  - Thermal shift assay can be used for the high-throughput screening of
      pharmacological chaperones. These drugs are small molecules that bind a mutant
      protein and stabilize it. We demonstrated the robustness, reproducibility and
      versatility of the method using two molecules that are in clinical trial for
      Fabry or Pompe disease, Deoxygalactonojirimycin and N-Butyldeoxynojirimycin, and
      their target enzymes, lysosomal alpha-galactosidaseA and alpha-glucosidase, as
      test cases. We assessed the influence of solvents and of scanning rate on the
      measures. We showed that a value that is equivalent to the melting temperature
      can be obtained by the first derivatives of raw data. We discuss the advantages
      of the method and the precaution to be taken in running the experiments.

PMID- 25845368
TI  - Mechano-sensitive nociceptors are required to detect heat pain thresholds and
      cowhage itch in human skin.
AB  - BACKGROUND: Mechano-sensitive and mechano-insensitive C-nociceptors in human skin
      differ in receptive field sizes and electrical excitation thresholds, but their
      distinct functional roles are yet unclear. METHODS: After blocking the lateral
      femoral cutaneous nerve (NCFL) in eight healthy male subjects (3-mL Naropin((r))
      1%), we mapped the skin innervation territory being anaesthetic to mechanical pin
      prick but sensitive to painful transcutaneous electrical stimuli. Such
      'differentially anaesthetic zones' indicated that the functional innervation with
      mechano-sensitive nociceptors was absent but the innervation with mechano
      insensitive nociceptors remained intact. In these areas, we explored heat pain
      thresholds, low pH-induced pain, cowhage- and histamine-induced itch, and axon
      reflex flare. RESULTS: In differentially anaesthetic skin, heat pain thresholds
      were above the cut-off of 50 degrees C (non-anaesthetized skin 47 +/- 0.4 degrees
      C). Pain ratings to 30 MUL pH 4 injections were reduced compared to non
      anaesthetized skin (48 +/- 9 vs. 79 +/- 6 VAS; p < 0.01). The axon reflex flare
      area did not differ between these zones (7.8 +/- 1.4 cm(2) vs. 8.3 +/- 0.5 cm(2)
      ). Histamine iontophoresis still caused pruritus in differentially anaesthetized
      skin in five of eight subjects (VAS 26 +/- 14), whereas itch upon cowhage
      spicules was absent (VAS 0 vs. 29 +/- 11 in non-anaesthetized skin). CONCLUSIONS:
      We conclude that activation of mechano-insensitive nociceptors is sufficient to
      provoke itch by histamine- and acid-induced pain. The mechano-sensitive
      nociceptors are crucial for cowhage-induced itch and for the assessment of heat
      pain thresholds.

PMID- 25845369
TI  - Contractile activity is required for Z-disc sarcomere maturation in vivo.
AB  - Sarcomere structure underpins structural integrity, signaling, and force
      transmission in the muscle. In embryos of the frog Xenopus tropicalis, muscle
      contraction begins even while sarcomerogenesis is ongoing. To determine whether
      contractile activity plays a role in sarcomere formation in vivo, chemical tools
      were used to block acto-myosin contraction in embryos of the frog X. tropicalis,
      and Z-disc assembly was characterized in the paralyzed dicky ticker mutant.
      Confocal and ultrastructure analysis of paralyzed embryos showed delayed Z-disc
      formation and defects in thick filament organization. These results suggest a
      previously undescribed role for contractility in sarcomere maturation in vivo.

PMID- 25845370
TI  - Characterization of adolescent and pediatric renal cell carcinoma: A report from
      the Children's Oncology Group study AREN03B2.
AB  - BACKGROUND: The current study was conducted to characterize the epidemiology,
      histology, and radiographic features of as well as the surgical approach to
      pediatric and adolescent renal cell carcinoma (pRCC). METHODS: pRCC cases
      prospectively enrolled on the Children's Oncology Group study AREN03B2 underwent
      central pathology, radiology, surgery, and oncology review. RESULTS: As of June
      2012, 120 of a total of 3250 patients enrolled on AREN03B2 (3.7%) were found to
      have unilateral RCC (median age, 12.9 years [range, 1.9-22.1 years]; 52.5% were
      female). Central review classified these as translocation morphology (56
      patients), papillary (20 patients), renal medullary carcinoma (13 patients),
      chromophobe (4 patients), oncocytoma (1 patient), conventional clear cell (1
      patient), and RCC not otherwise specified (25 patients). Lymph node (LN)
      involvement (N+) was found in 35 of 73 cases (47.9%) for which LNs were sampled,
      including 19 of 40 cases with primary tumors measuring <7 cm (47.5%). Using a
      size cutoff of 1 cm, imaging detection of LN involvement had a sensitivity of
      57.14% (20 of 35 cases; 95% CI, 39.35%-73.68%) and a specificity of 94.59% (35 of
      37 cases; 95% CI, 81.81%-99.34%). Distant metastases were present in 23 cases
      (19.2%). Initial surgery was radical nephrectomy in 88 patients (73.3%), nephron
      sparing surgery in 18 patients (15.0%), and biopsy in 14 patients (11.7%).
      Compared with patients undergoing radical nephrectomy, those treated with nephron
      sparing surgery were less likely to have LNs sampled (6 of 18 patients [33.3%] vs
      65 of 88 patients [73.9%]; P = .002). CONCLUSIONS: Translocation RCC is the most
      common form of pediatric and adolescent RCC. Lymph node disease is common and
      observed among patients with small primary tumors. Imaging has a high specificity
      but relatively low sensitivity for the detection of such lymph node disease.
      Failure to sample LNs results in incomplete staging and potentially inadequate
      disease control for younger patients with RCC.

PMID- 25845372
TI  - PGE2 MEDIATES OENOCYTOID CELL LYSIS VIA A SODIUM-POTASSIUM-CHLORIDE
      COTRANSPORTER.
AB  - Prostaglandin E2 (PGE2 ) mediates immune responses of the beet armyworm,
      Spodoptera exigua, including oenocytoid cell lysis (a class of lepidopteran
      hemocytes: OCL) via its specific membrane receptor to release inactive
      prophenoloxidase (PPO) into hemolymph. PPO is activated into phenoloxidase in the
      plasma to play crucial roles in the immune responses of S. exigua. The mechanism
      of OCL has not been elucidated, however we posed the hypothesis that a rapid
      accumulation of sodium ions within the oenocytoids allows a massive influx of
      water by the ion gradient, which leads to the cell lysis. It remains unclear
      which sodium channel is responsible for the OCL in response to PGE2 . This study
      identified a specific sodium channel called sodium-potassium-chloride
      cotransporter 1 (Se-NKCC1) expressed in hemocytes of S. exigua and analyzed its
      function in the OCL in response to PGE2 . Se-NKCC1 encodes a basic membrane
      protein (pI value = 8.445) of 1,066 amino acid residues, which contains 12
      putative transmembrane domains. Se-NKCC1 was expressed in all developmental
      stages and tissues. qPCR showed that bacterial challenge significantly induced
      its expression. A specific inhibitor of NKCC, bumetanide, prevented the OCL in a
      dose-dependent manner. When RNA interference (RNAi) using double-stranded RNA
      specific to Se-NKCC1 suppressed its expression, the OCL and PPO activation were
      significantly inhibited in response to PGE2 . The RNAi treatment also reduced
      nodule formation to bacterial challenge. These results suggest that Se-NKCC1 is
      associated with OCL by facilitating inward transport of ions in response to PGE2
      . 

PMID- 25845374
TI  - Population Approaches for Detecting Glucose Disorders.
AB  - Globally, 382 million adults aged 20-79 years are estimated to have diabetes and
      46% are unaware of their condition. Another 316 million adults are at increased
      risk of developing diabetes. Although there are suggestions that diabetes and
      related complications can be prevented through early detection, lifestyle
      intervention and/or treatment, universal screening for diabetes has not been
      adopted. There are, instead, recommendations for a multi-step screening approach,
      which include identifying people at risk of diabetes through non-invasive methods
      such as a risk assessment tool or presence of diabetes risk factors, followed by
      blood testing for the at risk group and diagnostic blood testing for those
      screened positive for diabetes. Diabetes screening initiatives have been studied
      in different medical, health and community settings and some have targeted high
      risk populations. Most of these screening initiatives, however, have common
      limitations such as low follow-up rate with primary care providers for those who
      screen positive, abnormal screening result not communicated to the at risk
      person's primary care provider, failure to provide appropriate follow-up for
      patients with abnormal screening results, time and cost as barriers for both
      screening providers and people invited for screening, and low acceptance of the
      oral glucose tolerance test. If these common limitations can be addressed,
      diabetes screening initiatives have the potential to detect undiagnosed diabetes
      in most populations. 

PMID- 25845371
TI  - Familial Ehlers-Danlos syndrome with lethal arterial events caused by a mutation
      in COL5A1.
AB  - Different forms of Ehlers-Danlos syndrome (EDS) exist, with specific phenotypes
      and associated genes. Vascular EDS, caused by heterozygous mutations in the
      COL3A1 gene, is characterized by fragile vasculature with a high risk of
      catastrophic vascular events at a young age. Classic EDS, caused by heterozygous
      mutations in the COL5A1 or COL5A2 genes, is characterized by fragile,
      hyperextensible skin and joint laxity. To date, vessel rupture in four unrelated
      classic EDS patients with a confirmed COL5A1 mutation has been reported. We
      describe familial occurrence of a phenotype resembling vascular EDS in a mother
      and her two sons, who all died at an early age from arterial ruptures. Diagnostic
      Sanger sequencing in the proband failed to detect aberrations in COL3A1, COL1A1,
      COL1A2, TGFBR1, TGFBR2, SMAD3, and ACTA2. Next, the proband's DNA was analyzed
      using a next-generation sequencing approach targeting 554 genes linked to
      vascular disease (VASCULOME project). A novel heterozygous mutation in COL5A1 was
      detected, resulting in an essential glycine substitution at the C-terminal end of
      the triple helix domain (NM_000093.4:c.4610G>T; p.Gly1537Val). This mutation was
      also present in DNA isolated from autopsy material of the index's brother. No
      material was available from the mother, but the mutation was excluded in her
      parents, siblings and in the father of her sons, suggesting that the COL5A1
      mutation occurred in the mother's genome de novo. In conclusion, we report
      familial occurrence of lethal arterial events caused by a COL5A1 mutation.

PMID- 25845375
TI  - The ultrasound-guided fat transplantation.

PMID- 25845376
TI  - Personalized Strategies to Activate and Empower Patients in Health Care and
      Reduce Health Disparities.
AB  - Designing culturally sensitive personalized interventions is essential to sustain
      patients' involvement in their treatment and encourage patients to take an active
      role in their own health and health care. We consider patient activation and
      empowerment as a cyclical process defined through patient accumulation of
      knowledge, confidence, and self-determination for their own health and health
      care. We propose a patient-centered, multilevel activation and empowerment
      framework (individual-, health care professional-, community-, and health care
      delivery system-level) to inform the development of culturally informed
      personalized patient activation and empowerment (P-PAE) interventions to improve
      population health and reduce racial and ethnic disparities. We discuss relevant
      Affordable Care Act payment and delivery policy reforms and how they affect
      patient activation and empowerment. Such policies include Accountable Care
      Organizations and value-based purchasing, patient-centered medical homes, and the
      community health benefit. Challenges and possible solutions to implementing the P
      PAE are discussed. Comprehensive and longitudinal data sets with consistent P-PAE
      measures are needed to conduct comparative effectiveness analyses to evaluate the
      optimal P-PAE model. We believe the P-PAE model is timely and sustainable and
      will be critical to engaging patients in their treatment, developing patients'
      abilities to manage their health, helping patients express concerns and
      preferences regarding treatment, empowering patients to ask questions about
      treatment options, and building up strategic patient-provider partnerships
      through shared decision making. 

PMID- 25845377
TI  - A brief journey through the immune system.
AB  - This review serves as an introduction to an Immunology Series for the
      Nephrologist published in CJASN. It provides a brief overview of the immune
      system, how it works, and why it matters to kidneys. This review describes in
      broad terms the main divisions of the immune system (innate and adaptive), their
      cellular and tissue components, and the ways by which they function and are
      regulated. The story is told through the prism of evolution in order to relay to
      the reader why the immune system does what it does and why imperfections in the
      system can lead to renal disease. Detailed descriptions of cell types, molecules,
      and other immunologic curiosities are avoided as much as possible in an effort to
      not detract from the importance of the broader concepts that define the immune
      system and its relationship to the kidney. 

PMID- 25845378
TI  - Biological activation of zirconia surfaces by chemical modification with IGF-1.
AB  - The purpose of this study was to improve the adhesion and extension of human
      gingival epithelial cells (HGECs) to the yttria-stabilized zirconia polycrystal
      (Y-TZP) surfaces by immobilization of insulin-like growth factor 1 (IGF-1).
      Surface analyses by Fourier transform infrared spectroscopy (FTIR) and X-ray
      photoelectron spectroscopy (XPS) showed that IGF-1 was successfully immobilized
      on the Y-TZP surfaces. There was no significant difference between the number of
      cells attached to the IGF-1-immobilized Y-TZP surfaces and on the as-polished Y
      TZP surfaces either at 3 or 72 h. However, IGF-1-immobilized Y-TZP surfaces
      yielded a significantly higher expression of integrin beta4 mRNA and laminin-5
      mRNA, and enhanced adhesion strength of HGECs after 72 h of incubation. There was
      no difference between the amount of adhered Streptococcus gordonii (S. gordonii)
      found on the IGF-1-immobilized Y-TZP surfaces and on the as-polished Y-TZP
      surfaces. These results suggested that the IGF-1-immobilized Y-TZP surfaces
      developed using the method reported herein enhanced the adhesion and extension of
      HGECs to the Y-TZP surfaces without enhancing S. gordonii adhesion.

PMID- 25845379
TI  - Tribbles homolog 3 is induced by high glucose and associated with apoptosis in
      human endothelial cells.
AB  - Tribbles homolog 3 (TRIB3) is an intracellular kinase-like molecule that modifies
      cellular survival and metabolism. The present study aimed to investigate the
      function of TRIB3 regulation in the process of high glucose-induced apoptosis in
      endothelial cells, with the aim of identifying a novel intervention target for
      the prevention and treatment of diabetes mellitus. Human umbilical vein
      endothelial cells (HUVECs) grown in medium with various concentrations of glucose
      (5.5, 10, 20, 30 and 40 mmol/l) were assessed for mRNA expression of TRIB1, TRIB2
      and TRIB3 using reverse transcription quantitative polymerase chain reaction. In
      addition, protein expression of TRIB3 was examined using western blot analysis.
      Immunofluorescence staining was performed in order to determine the distribution
      and localization of TRIB3 in HUVECs. Furthermore, cells grown in normal (5.5
      mmol/l) or high glucose (HG; 30 mmol/l) medium were subjected to TRIB3 inhibition
      through small interfering (si)RNA knockdown. These cells were then examined in
      order to determine whether TRIB3 upregulation was associated with endothelial
      cell apoptosis. HUVECs treated with 30 and 40 mmol/l glucose for 48 h and 72 h
      showed significantly lower survival rates compared with those treated with normal
      glucose levels. In addition, slight but not significant increases in TRIB1 and
      TRIB2 mRNA expression were observed in HUVECs incubated with various
      concentrations of glucose for different durations. By contrast, TRIB3 mRNA
      expression was increased 7.2-fold following incubation with HG. Western blot
      analysis revealed a 5.44-fold increase in TRIB3 protein levels in cells grown in
      HG medium for 24 h compared with those grown in normal medium. Immunostaining
      assays revealed a markedly higher and well-defined nucleolar fluorescence
      intensity for TRIB3 expression at 24 h in HG medium compared with that of the
      control group. Furthermore, the apoptotic rate of HG-treated TRIB3 siRNA
      transfected HUVECs was significantly increased compared with that of those
      transfected with control siRNA In conclusion, the results of the present study
      suggested that TRIB3 was associated with high glucose-induced HUVECs apoptosis,
      which was attenuated following transfection with TRIB3 siRNA.

PMID- 25845380
TI  - Quercetin in prostate cancer: Chemotherapeutic and chemopreventive effects,
      mechanisms and clinical application potential (Review).
AB  - The morbidity and mortality of prostate cancer have been increasing recently, and
      the comprehensive treatment for prostate cancer is unable to achieve satisfactory
      outcomes. Quercetin is a natural flavonoid compound that has attracted increased
      interest and attention due to its anticancer activity. In vitro and in vivo
      studies have verified that quercetin effectively inhibits prostate cancer via
      various mechanisms. Clinical trails concerning the pharmacokinetics and
      application of quercetin in humans have also obtained promising results.
      Meanwhile, epidemiologic studies have demonstrated a negative association between
      quercetin intake and prostate cancer incidence and have suggested a
      chemopreventive effect of quercetin on prostate cancer that has been exhibited in
      animal experiments. The main issue concerning quercetin utilization is its low
      bioavailability. Therefore, solutions to the issues concerning its use such as
      alteration of the molecular structure and combination therapy are in the
      exploratory stage. In the present review, the most important aspects of
      chemotherapeutic and chemopreventive effects, mechanisms and clinical application
      potential of quercetin in prostate cancer are summarized.

PMID- 25845381
TI  - Biological Control of Patulin by Antagonistic Yeast: A case study and possible
      model.
AB  - The occurrence of patulin in fresh apples and apple products is a great burden
      from health, safety and economic perspectives. Attempts to prevent patulin
      accumulation in fruits might lead to the excessive use of fungicides. Therefore,
      guaranteeing the safety of apple foods is crucial for the international apple
      industry. Recently, literature revealed that application of antagonistic yeasts
      and other BCAs have been able to disrupt the process of fungal infection and
      patulin production in apples. Although, over the years the effect of interaction
      between BCAs and fungi on patulin production has been reported, the exact
      mechanism(s) of their action remain unclear. Here, the review focused on
      toxicology and occurrence of PAT; research advances made over the past few years
      on the interaction between antagonistic yeast, fruits and patulin-producing
      fungi; the prevalence of patulin in apple fruits and products and the
      implications of synthetic-fungicide applications. In addition, attention was
      focused on the mechanism(s) and the enhancement of the biocontrol efficacy of
      antagonistic for patulin control. 

PMID- 25845382
TI  - Inhibitory effects of proton beam irradiation on integrin expression and
      signaling pathway in human colon carcinoma HT29 cells.
AB  - Proton radiotherapy has been established as a highly effective modality used in
      the local control of tumor growth. Although proton radiotherapy is used worldwide
      to treat several types of cancer clinically with great success due to superior
      targeting and energy deposition, the detailed regulatory mechanisms underlying
      the functions of proton radiation are not yet well understood. Accordingly, in
      the present study, to assess the effects of proton beam on integrin-mediated
      signaling pathways, we investigated the expression of integrins related to tumor
      progression and integrin trafficking, and key molecules related to cell adhesion,
      as well as examining phosphorylation of signaling molecules involved in integrin
      mediated signaling pathways. Proton beam irradiation inhibited the increase in 12
      O-tetradecanoylphorbol-13-acetate (TPA)-induced integrin beta1 protein expression
      and the gene expression of members of the integrin family, such as alpha5beta1,
      alpha6beta4, alphavbeta3, and alphavbeta6 in human colorectal adenocarcinoma HT
      29 cells. Simultaneously, the gene expression of cell adhesion molecules, such as
      FAK and CDH1, and integrin trafficking regulators, such as RAB4, RAB11, and HAX1,
      was decreased by proton beam irradiation. Moreover, proton beam irradiation
      decreased the phosphorylation of key molecules involved in integrin signaling,
      such as FAK, Src, and p130Cas, as well as PKC and MAPK, which are known as
      promoters of cell migration, while increased the phosphorylation of AMPK and the
      gene expression of Rab IP4 involved in the inhibition of cell adhesion and cell
      spreading. Taken together, our findings suggest that proton beam irradiation can
      inhibit metastatic potential, including cell adhesion and migration, by
      modulating the gene expression of molecules involved in integrin trafficking and
      integrin-mediated signaling, which are necessary for tumor progression. 

PMID- 25845384
TI  - Particulate matter 2.5 induces autophagy via inhibition of the
      phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin kinase signaling
      pathway in human bronchial epithelial cells.
AB  - Particulate matter 2.5 (PM2.5) is a significant risk factor for asthma. A recent
      study revealed that autophagy was associated with asthma pathogenesis. However,
      the specific mechanisms underlying PM2.5-induced autophagy in asthma have
      remained elusive. In the present study, PM2.5-induced autophagy was evaluated in
      Beas-2B human bronchial epithelial cells and the potential molecular mechanisms
      were investigated. Using electron microscopy, immunofluorescence staining and
      immunoblot studies, it was confirmed that PM2.5 induced autophagy in Beas-2B
      cells as a result of PM2.5-mediated inhibition of the phosphatidylinositol 3
      kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway in Beas-2B cells.
      LY294002, a PI3K inhibitor, reduced the accumulation of microtubule-associated
      protein 1 light chain 3 II and attenuated the effect of PM2.5. Phosphorylated (p
      )p38, p-extracellular signal-regulated kinase and p-c-Jun N-terminal kinase were
      dephosphorylated following exposure to PM2.5. The roles of p53, reactive oxygen
      species scavenger tetramethylthiourea and autophagy inhibitor 3-methyladenine in
      PM2.5-induced autophagy in Beas-2B cells were also investigated. The results
      suggested that the PI3K/Akt/mTOR signaling pathway may be a key contributor to
      PM2.5-induced autophagy in Beas-2B cells. The results of the present study
      therefore provided an a insight into potential future clinical applications
      targeting these signaling pathways, for the prevention and/or treatment of PM2.5
      induced lung diseases.

PMID- 25845385
TI  - Sequence and organization of the complete mitochondrial genome of the marsh tit
      Poecile palustris (Aves: Paridae).
AB  - The complete mitochondrial genome of the marsh tit Poecile palustris (Linnaeus,
      1758) was sequenced using a combined Illumina and Sanger sequencing approach.
      Using the known sequence of Poecile atricapillus Linnaeus, 1766 (Paridae)
      homologous NGS reads were identified and assembled. The genome is 16,824 bp in
      length and includes 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer
      RNA genes and a control region. Gene order resembles that of the standard avian
      gene order. The base composition of the genome is A (29.15%), T (22.50%), C
      (33.61%) and G (14.73%). The control region between tRNA(Glu) and tRNA(Phe) is
      composed of 1240 bp with no obvious repetitive motifs.

PMID- 25845383
TI  - Long-term health consequences of premature or early menopause and considerations
      for management.
AB  - AIM: To review the current evidence concerning the long-term harmful effects of
      premature or early menopause, and to discuss some of the clinical implications.
      MATERIAL AND METHODS: Narrative review of the literature. RESULTS: Women
      undergoing premature or early menopause, either following bilateral salpingo
      oophorectomy or because of primary ovarian insufficiency, experience the early
      loss of estrogen and other ovarian hormones. The long-term consequences of
      premature or early menopause include adverse effects on cognition, mood,
      cardiovascular, bone, and sexual health, as well as an increased risk of early
      mortality. The use of hormone therapy has been shown to lessen some, although not
      all of these risks. Therefore, multiple medical societies recommend providing
      hormone therapy at least until the natural age of menopause. It is important to
      individualize hormone therapy for women with early estrogen deficiency, and
      higher dosages may be needed to approximate physiological concentrations found in
      premenopausal women. It is also important to address the psychological impact of
      early menopause and to review the options for fertility and the potential need
      for contraception, if the ovaries are intact. CONCLUSIONS: Women who undergo
      premature or early menopause should receive individualized hormone therapy and
      counseling.

PMID- 25845386
TI  - Mitochondrial DNA alterations correlate with the pathological status and the
      immunological ER, PR, HER-2/neu, p53 and Ki-67 expression in breast invasive
      ductal carcinoma.
AB  - We analyzed the changes in mitochondrial DNA (mtDNA) copy numbers and the
      shifting of mtDNA D310 sequence variations (D310 mutation) with their
      relationships to pathological status and the expression levels of estrogen
      receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor
      2 (HER-2/neu), tumor-suppressor protein p53 and cellular proliferation protein Ki
      67 in breast invasive ductal carcinoma (BIDC), respectively. Fifty-one paraffin
      embedded BIDCs and their paired non-cancerous breast tissues were dissected for
      DNA extraction. The mtDNA copy number and mtDNA D310 sequence variations were
      determined by quantitative real-time polymerase chain reaction (q-PCR) and PCR
      based direct sequencing, respectively. The expression levels of ER, PR, HER
      2/neu, p53 and Ki-67 were determined by immunohistochemical (IHC) staining.
      Compared to the paired non-cancerous breast tissues, 24 (47.1%) BIDCs had
      elevated mtDNA copy numbers and 29 (56.9%) harbored mtDNA D310 mutations.
      Advanced T-status (p=0.056), negative-ER (p=0.005), negative-PR (p=0.007),
      positive-p53 (p=0.050) and higher Ki-67 (p=0.004) expressions were related to a
      higher mtDNA copy ratio. In addition, advanced T-status (p=0.019) and negative
      HER-2/neu expression (p=0.061) were associated with mtDNA D310 mutations. In
      conclusion, higher mtDNA copy ratio and D310 mutations may be relevant biomarkers
      correlated with pathological T-status and the expression levels of ER, PR, HER
      2/neu, p53 and Ki-67 in BIDCs. 

PMID- 25845387
TI  - Long non-coding RNA ANRIL predicts poor prognosis and promotes
      invasion/metastasis in serous ovarian cancer.
AB  - Recent studies have highlighted the role of long non-coding RNAs (lncRNAs) in
      carcinogenesis and have suggested that genes of this class might be used as
      biomarkers in cancer. However, whether lncRNAs are involved in serous ovarian
      cancer (SOC) remains largely unknown. In the present study, we focused on lncRNA
      antisense non-coding RNA in the INK4 locus (ANRIL) and investigated its
      expression pattern, clinical significance, and biological function in SOC. We
      found that ANRIL levels were elevated in SOC tissues compared with normal
      controls and were highly correlated with advanced FIGO stage, high histological
      grade, lymph node metastasis, and poor prognosis. Multivariate analysis further
      revealed that ANRIL is an independent prognostic factor for predicting overall
      survival of SOC patients. In vitro, we compared differential ANRIL levels between
      SOC parental cell lines (SK-OV-3, HO8910) and highly metastatic sublines (SK-OV
      3.ip1, HO8910-PM). Notably, ANRIL was highly expressed in both SK-OV-3.ip1 cells
      and HO8910-PM cells. SiRNA-mediated ANRIL silencing in these cells impaired cell
      migration and invasion. Based on the metastasis-related mRNA microarray analysis
      and subsequent western blotting confirmation, we found that MET and MMP3 are key
      downstream genes of ANRIL involved in SOC cell migration/invasion. Together, our
      data suggest that lncRNA ANRIL plays an important role in SOC invasion/metastasis
      and could represent a novel biomarker for predicting poor survival as well a
      promising therapeutic target.

PMID- 25845388
TI  - The utility of measuring anti-Mullerian hormone in predicting menopause.
AB  - Menopause is a relevant phase in a woman's reproductive life. Accurate estimation
      of the time of menopause could improve the preventive management of women's
      health. Reproductive hormones reflect the activity of follicle pools and provide
      information about ovarian aging. Anti-Mu llerian hormone (AMH) is secreted from
      small antral follicles and its level is correlated to the ovarian reserve. AMH
      declines with age, and data suggest that it can provide information on menopausal
      age and reproductive lifespan. Serum AMH levels become low approximately 5 years
      before the final menstrual period and are undetectable in postmenopausal women.
      The majority of studies indicate that AMH is relatively stable throughout the
      menstrual cycle; however, there are interindividual variabilites of serum AMH
      concentration under different conditions. AMH is an independent predictor of time
      to menopause. AMH coupled with age for menopause prediction provides stronger
      information than using age alone. Ongoing research is focused on constructing a
      multivariate model including AMH values, genes related to follicular recruitment
      and maternal age of menopause that would predict more precisily time to
      menopause. 

PMID- 25845390
TI  - HIV Type 1 Subtype A1 Dominates in Armenia.
AB  - OBJECTIVE: There is scarce information about the molecular epidemiology of HIV
      infection in Armenia (former USSR). The objective of this work was to estimate
      the distribution of HIV-1 subtypes in this country and get any information about
      HIV drug resistance in naIve patients. DESIGN: A joint study involving 78
      patients was carried out in Yerevan, Armenia and Moscow, Russia in 2009-2013. The
      cohort studies included mostly IDUs (28.2%) and heterosexuals (69.2%). RESULTS:
      The phylogenetic analyses based on population sequencing of partial pol gene
      found subtype A1 being the most prevalent (92.3%), followed by subtype B (3.9%).
      The HIV-1 tropism inferred from env V3-loop sequences was determined in 27
      samples, among them R5-tropic viruses were found in 13 (48.1%) patients and X4-
      variants--in 14 (51.9%) patients. The prevalence of drug resistance in naive
      patients was low (1.5%) with the only one mutation K219Q found. CONCLUSION: The
      composition and distribution of HIV-1 genetic variants in Armenia are evidently
      influenced by the Russian and other FSU countries epidemic, due to the
      significant volume of Armenian migrant/re-emigrant flows. Continued surveillance
      of HIV-1 circulating subtypes and drug resistance in Armenia is important for the
      proper management of HIV infection in this country.

PMID- 25845389
TI  - HIV Replication at Low Copy Number and its Correlation with the HIV Reservoir: A
      Clinical Perspective.
AB  - The efficacy of combination therapy (antiretroviral therapy--ARV) is demonstrated
      by the high rates of viral suppression achieved in most treated HIV patients.
      Whereas contemporary treatments may continuously suppress HIV replication, they
      do not eliminate the latent reservoir, which can reactivate HIV infection if ARV
      is discontinued. The persistence of HIV proviral DNA and infectious viruses in
      CD4+ T cells and others cells has long been considered a major obstacle in
      eradicating the HIV virus in treated patients. Moreover, recent studies have
      demonstrated the persistence of HIV replication at low copies in most patients on
      suppressive ARV. The source of this 'residual viraemia' and whether it declines
      over years of therapy remain unknown. Similarly, little is known regarding the
      biological relationships between the HIV reservoir and viral replication at low
      copies. The question of whether this 'residual viraemia' represents active
      replication or the release of non-productive virus from the reservoir has not
      been adequately resolved. From a clinical perspective, both the quantification of
      the HIV reservoir and the detection of low levels of replication in full
      responder patients on prolonged ARV may provide important information regarding
      the effectiveness of treatment and the eradication of HIV. To date, the
      monitoring of these two parameters has been conducted only for research purposes;
      the routine use of standardised tests procedure is lacking. This review aims to
      assess the current data regarding the correlation between HIV replication at low
      copies and the HIV reservoir and to provide useful information for clinicians.

PMID- 25845391
TI  - HIV-1 Early Infant Diagnosis is an Effective Indicator of the Prevention of
      Mother-to-Child Transmission Program Performance: Experience from Cameroon.
AB  - BACKGROUND: Despite improvement in HIV prevention of mother-to-child transmission
      (PMTCT), there are still over 1,500 African infants newly infected daily. PMTCT
      elimination requires antiretroviral therapy (ART) throughout pregnancy and
      breastfeeding periods, while early infant diagnosis (EID) of HIV implies early
      treatment for those infected. Our study aimed at assessing the utility of EID
      program data in evaluating the implementation of PMTCT program in Cameroon, and
      in identifying the efficacy of existing PMTCT interventions and breastfeeding
      options on the events of HIV vertical transmission. METHODS: A study was
      conducted from 2010-2011 using PMTCT data from EID sites of six regions of
      Cameroon. PMTCT ARV regimens, breastfeeding options, and the child's HIV DNA
      polymerase chain reaction (PCR) results were recorded. Statistical analyses were
      performed using Mann Whitney U and Fisher exact tests, with p<0.05 considered
      significant. RESULTS: A total of 2,505 mother-child pairs received ART, resulting
      is 4.3% (93) vertical transmission, against 31.3% (284/906) among mother-child
      pairs without exposure to any PMTCT intervention; p<0.00001. A statistically
      significant difference (p<0.00001) was also found between formula feeding (FF)
      (5.9%) versus exclusive breastfeeding (EBF) (12.5%), as well as between EBF
      versus mixed feeding (MF) (30%). With FF, when both mother-child pairs received
      PMTCT, only 2.9% (47/1603) vertical transmission was recorded versus 19.9%
      (48/241) for mother-child pairs without intervention; p<0.00001. Transmission
      rates were similar across infant age range [2.7% (10/376) for age <=6 weeks,
      versus 2.5% (43/1807) for age >6 weeks-6 months]. Interestingly, babies aged 6
      weeks receiving FF showed a significantly lower transmission rate (3.2%, 9/277)
      as compared to their counterparts with EBF (7.7%, 12/156); p<0.00001. CONCLUSION:
      Using EID dataset, it appears that considerable reduction in HIV MTCT may be
      achievable through access to ARV (option B+) and adequate infant feeding option
      (especially FF) in Cameroon. EID programme is therefore an effective routine
      approach for PMTCT programme evaluation in resource-limited settings.

PMID- 25845392
TI  - Performance of Genotype MTBDRplus in the Detection of Resistance to Rifampicin
      and Isoniazid Among Clinical Mycobacteria Isolates in Ilorin, Nigeria.
AB  - BACKGROUND: Performance of Genotype MTBDRplus assay against Lowenstein Jensen
      (LJ) proportion method of Drug Susceptibility Testing (DST) in detection of
      resistance among clinical mycobacteria isolates to rifampicin (RMP) and isoniazid
      (INH) was evaluated in Ilorin, Nigeria. METHODS: This retrospective study
      characterized one hundred mycobacteria isolates from pulmonary TB patients,
      stored on LJ medium and subcultured unto fresh LJ slants before being genotyped
      using MTBDRplus assay. DST was performed on the isolates against RMP, INH,
      Ethambutol and Streptomycin. RESULTS: Genotype MTBDRplus identified 97% and 3% of
      the 100 isolates as Mycobacterium tuberculosis Complex (MTBC) and Non-Tuberculous
      Mycobacteria (NTM) respectively. Fourteen of the isolates, (14%) were resistant
      to RMP while 86% were sensitive by the genotypic method. Three of these 14 RMP
      resistant isolates were NTMs while 11 were MTBC. Twelve (12%) of the 100 isolates
      were resistant to INH. Three INH-resistant isolates were NTMs, and 9 were MTBC.
      Phenotypically and genotypically, the 3 NTMs were resistant to RMP and INH and
      ten of the 97 MTBC strains were RMP-resistant. One RMP-phenotypically-sensitive
      strain was genotypically resistant to RMP. Six of the MTBC isolates were
      resistant to both RMP and INH by both methods. Most mutations occurred in the S
      531L and S315T1 codons of rpoB and KatG genes of RMP and INH, respectively.
      CONCLUSION: The high specificity and positive predictive values recorded by
      MTBDRplus in our study make it suitable for use in the programmatic management of
      drug-resistant TB in resource-limited settings.

PMID- 25845393
TI  - Socio-Demographic and Adherence Factors Associated with Viral Load Suppression in
      HIV-Infected Adults Initiating Therapy in Northern Nigeria: A Randomized
      Controlled Trial of a Peer Support Intervention.
AB  - BACKGROUND: Virological suppression is the main goal of antiretroviral therapy.
      To achieve this goal, efficient interventions that promote treatment adherence
      are needed. This study was aimed at exploring the impact of peer-education on
      virological outcomes in Northern Nigeria. METHODS: A randomized controlled trial
      (RCT) among patients receiving antiretroviral treatment was conducted in 2 phases
      between August 2006 and January 2008 in the "largely Muslim" Northern Nigeria.
      Participants were randomized into one of three intervention arms: standard of
      care arm, a second arm which included daily reminders via alarm and follow-up
      calls from peer-educators, and adherence support by a home-based treatment
      partner; and a third arm which included second arm activities, plus home visits
      by peer-educators. We evaluated sociodemographic factors and adherence levels,
      measured using self-report and pharmacy (Rx) refill rates, as risk factors for
      viral load (VL) suppression. RESULTS: Of the 600 participants (43% males), 276
      were observed till the end of the study. There were no significant differences in
      mean log 10 VL between the intervention groups. At the end of entire follow-up
      period, 83% (229/276) who were not lost to follow-up achieved undetectable VL (<
      400 copies/ml). In the multivariable analysis, age between 30-34 years (vs 18-24
      years) and both baseline CD4 ranges between 100-199 cells/mm(3) or 200-349
      cells/mm(3) (vs CD4 <100 cells/mm(3)) as positively associated with VL
      suppression while poor self-reported adherence and <95% Rx refill rates were
      negatively associated with VL suppression. CONCLUSION: High levels of viral
      suppression and low prevalence of drug resistance mutations (DRMs) were seen in
      this cohort participating in an ART adherence study in Northern Nigeria. Self
      reported good adherence and optimal Rx refill rates were reported as significant
      predictors of VL suppression. Our findings indicate that ART adherence will
      improve significantly regardless of whether HIV-infected adults received peer
      education-based medication adherence interventions or standard of care services.

PMID- 25845394
TI  - Carbon quantum dots and applications in photocatalytic energy conversion.
AB  - Quantum dots (QDs) generally refer to nanoscale particles of conventional
      semiconductors that are subject to the quantum-confinement effect, though other
      nanomaterials of similar optical and redox properties are also named as QDs even
      in the absence of strictly defined quantum confinement. Among such nanomaterials
      that have attracted tremendous recent interest are carbon dots, which are small
      carbon nanoparticles with some form of surface passivation, and graphene quantum
      dots in various configurations. In this article, we highlight these carbon-based
      QDs by focusing on their syntheses, on their photoexcited state properties and
      redox processes, and on their applications as photocatalysts in visible-light
      carbon dioxide reduction and in water-splitting, as well as on their mechanistic
      similarities and differences. 

PMID- 25845395
TI  - Microencapsulation of recombinant adenovirus within poly-DL-lactide-poly(ethylene
      glycol) microspheres for enhanced gene transfection efficiency and inhibitory
      effects on hepatocellular carcinoma cells in vitro.
AB  - When gene therapy is performed for the treatment of malignant tumors, gene
      transfer efficiency and selectivity are highly important. Polymer vehicle
      microspheres are a novel type of therapy, which have been developed rapidly in
      recent years and are able to control drug release, prolong the biological half
      life of drugs, decrease side effects and achieve targeted delivery. The present
      study was designed to construct a polymer microsphere-encapsulated recombinant
      adenovirus with human tissue inhibitors of the matrix metalloproteinase-1 (TIMP
      1) gene, and to discuss its characterization for the purpose of liver cancer gene
      therapy. The microsphere was prepared from biodegradable poly-DL-lactide
      poly(ethylene glycol) (PELA) encapsulating rAdTIMP-1, the recombinant adenovirus
      carrying TIMP-1, by a modified double-emulsion method. The particle morphology,
      diameter, virus encapsulation, loading rate and release kinetics of the rAd
      microspheres were determined in vitro. Hepatocellular carcinoma (HCC) HepG2 cells
      were transfected with the rAd-microsphere and the efficiency of transfection was
      assessed by fluorescent microscopy. The production and expression of TIMP-1 was
      identified by gelatin zymography and western blot analysis, and the invasiveness
      was detected by a matrigel matrix invasion assay. The microsphere encapsulating
      rAdTIMP-1 was successfully constructed with a diameter of 1.965 MUm,
      encapsulation efficiency of 60.0%, a viral load of 10.5 x 10(8)/mg, a virus
      release of ~60% within 120 h and a total release time of >240 h. The resultant
      rAd-microspheres were able to efficiently transfect HepG2 cells with the
      transfection efficiency enhanced by ~90%. As a result, the transfected HepG2
      cells had significantly increased TIMP-1 enzyme activity and the expression of
      TIMP-1 was detected by western blot analysis. In addition, the proliferation and
      invasion ability of the HCC cells was markedly inhibited by the rAd-microspheres.
      The resultant rAd-microspheres, PELA-encapsulated recombinant TIMP-1 adenovirus,
      had enhanced transfection efficiency and were able to markedly inhibit the in
      vitro biological behavior of HepG2 cells. This provides an experimental basis for
      this polymer application and may pave the way for prospective in vivo clinical
      trials and further comprehensive therapy for liver cancer.

PMID- 25845397
TI  - Reproducibility of Facial Soft Tissue Thickness Measurements Using Cone-Beam CT
      Images According to the Measurement Methods.
AB  - The purpose of this study was to establish the reproducibility of facial soft
      tissue (ST) thickness measurements by comparing three different measurement
      methods applied at 32 landmarks on three-dimensional cone-beam computed
      tomography (CBCT) images. Two observers carried out the measurements of facial ST
      thickness of 20 adult subjects using CBCT scan data, and inter- and intra
      observer reproducibilities were evaluated. The measurement method of
      "perpendicular to bone" resulted in high inter- and intra-observer
      reproducibility at all 32 landmarks. In contrast, the "perpendicular to skin"
      method and "direct" method, which measures a distance between one point on bone
      and the other point on skin, presented low reproducibility. The results indicate
      that reproducibility could be increased by identifying the landmarks on hard
      tissue images, rather than on ST images, and the landmark description used in
      this study can be used in the establishment of reliable tissue depth data using
      CBCT images. 

PMID- 25845396
TI  - Circadian Tick-Talking Across the Neuroendocrine System and Suprachiasmatic
      Nuclei Circuits: The Enigmatic Communication Between the Molecular and Electrical
      Membrane Clocks.
AB  - As with many processes in nature, appropriate timing in biological systems is of
      paramount importance. In the neuroendocrine system, the efficacy of hormonal
      influence on major bodily functions, such as reproduction, metabolism and growth,
      relies on timely communication within and across many of the brain's homeostatic
      systems. The activity of these circuits is tightly orchestrated with the animal's
      internal physiological demands and external solar cycle by a master circadian
      clock. In mammals, this master clock is located in the hypothalamic
      suprachiasmatic nucleus (SCN), where the ensemble activity of thousands of clock
      neurones generates and communicates circadian time cues to the rest of the brain
      and body. Many regions of the brain, including areas with neuroendocrine
      function, also contain local daily clocks that can provide feedback signals to
      the SCN. Although much is known about the molecular processes underpinning
      endogenous circadian rhythm generation in SCN neurones and, to a lesser extent,
      extra-SCN cells, the electrical membrane clock that acts in partnership with the
      molecular clockwork to communicate circadian timing across the brain is poorly
      understood. The present review focuses on some circadian aspects of reproductive
      neuroendocrinology and processes involved in circadian rhythm communication in
      the SCN, aiming to identify key gaps in our knowledge of cross-talk between our
      daily master clock and neuroendocrine function. The intention is to highlight our
      surprisingly limited understanding of their interaction in the hope that this
      will stimulate future work in these areas. 

PMID- 25845398
TI  - Nanoparticle Estrogen in Rat Spinal Cord Injury Elicits Rapid Anti-Inflammatory
      Effects in Plasma, Cerebrospinal Fluid, and Tissue.
AB  - Persons with spinal cord injury (SCI) are in need of effective therapeutics.
      Estrogen (E2), as a steroid hormone, is a highly pleiotropic agent; with anti
      inflammatory, anti-apoptotic, and neurotrophic properties, it is ideal for use in
      treatment of patients with SCI. Safety concerns around the use of high doses of
      E2 have limited clinical application, however. To address these concerns, low
      doses of E2 (25 MUg and 2.5 MUg) were focally delivered to the injured spinal
      cord using nanoparticles. A per-acute model (6 h after injury) was used to assess
      nanoparticle release of E2 into damaged spinal cord tissue; in addition, E2 was
      evaluated as a rapid anti-inflammatory. To assess inflammation, 27-plex
      cytokine/chemokine arrays were conducted in plasma, cerebrospinal fluid (CSF),
      and spinal cord tissue. A particular focus was placed on IL-6, GRO-KC, and MCP-1
      as these have been identified from CSF in human studies as potential biomarkers
      in SCI. S100beta, an additional proposed biomarker, was also assessed in spinal
      cord tissue only. Tissue concentrations of E2 were double those found in the
      plasma, indicating focal release. E2 showed rapid anti-inflammatory effects,
      significantly reducing interleukin (IL)-6, GRO-KC, MCP-1, and S100beta in one or
      all compartments. Numerous additional targets of rapid E2 modulation were
      identified including: leptin, MIP-1alpha, IL-4, IL-2, IL-10, IFNgamma, tumor
      necrosis factor-alpha, etc. These data further elucidate the rapid anti
      inflammatory effects E2 exerts in an acute rat SCI model, have identified
      additional targets of estrogen efficacy, and suggest nanoparticle delivered
      estrogen may provide a safe and efficacious treatment option in persons with
      acute SCI.

PMID- 25845399
TI  - Sesamin inhibits lipopolysaccharide-induced proliferation and invasion through
      the p38-MAPK and NF-kappaB signaling pathways in prostate cancer cells.
AB  - Sesamin, a lipid-soluble lignan, is one of the major constituents of sesame.
      Previous studies have reported that sesamin induces growth inhibition in human
      cancer cells, particularly prostate cancer cells. In the present study, we mainly
      explored the mechanism underlying the protective effect of sesamin on prostate
      cancer cell proliferation and invasion induced by lipopolysaccharide (LPS). We
      found that the proliferation of PC3 cells, as determined using the MTT assay, and
      the expression of cyclin D1, COX-2, Bcl-2 and survivin proteins elevated by LPS
      were distinctly inhibited by sesamin in a dose-dependent manner. Meanwhile, the
      ability of PC3 cell invasion, as determined using the Transwell assay and the
      expression of matrix metalloproteinase 9 (MMP-9), intercellular adhesion molecule
      1 (ICAM-1) and vascular endothelial growth factor (VEGF) proteins increased by
      LPS were obviously reduced by sesamin in a dose-dependent manner. In addition,
      the accumulation of TGF-alpha and interleukin-6 (IL-6) production induced by LPS
      in the culture supernatant was found to be decreased dose-dependently with
      sesamin pretreatment in PC3 cells using the enzyme-linked immunosorbent assay
      (ELISA) kit. Furthermore, phosphorylation of the p38 protein and nuclear factor
      (NF)-kappaB activity in the PC3 cells were enhanced by LPS and further inhibited
      with sesamin, SB203580 pretreatment or p38-siRNA transfection, respectively.
      Sesamin or SB203580 pretreatment obviously inhibited PC3 cells-derived tumor
      growth induced by LPS in vivo. Taken together, these results suggest that the
      potential ability of sesamin to downregulate the secretion of cytokines and the
      expression of cell proliferative- and invasive-related gene products induced by
      LPS was shown to be via the p38 mitogen-activated protein kinase (p38-MAPK) and
      NF-kappaB signaling pathways, which may be one of the mechanisms of the
      anticancer activity of this sesamin agent in prostate cancer cells.

PMID- 25845400
TI  - Polarized currents inhibit in vitro growth of bacteria colonizing cutaneous
      ulcers.
AB  - Infections caused by Staphylococcus aureus, Pseudomonas aeruginosa, and
      Escherichia coli are among the microorganisms that often lead to infection in
      pressure ulcers. Polarized current has emerged as a possible intervention to
      limit bacterial proliferation. We analyzed the effect of fixed diphasic - Bernard
      (FD-B) and high voltage monophasic pulsed (HVMP) currents on bacteria S. aureus
      ATCC 25923 (Gram +), P. aeruginosa ATCC 27853 (Gram -), and E. coli ATCC 25922
      (Gram -). After the bacterial strains were activated the bacteria were suspended
      in physiological solution (0.9%) and the concentration adjusted to 1.5 * 10(3)
      CFU/mL. The cultures were stimulated with FD-B current at (3, 6, and 9 mA, 100
      Hz, 15 and 30 minutes) and HVMP (32, 64, and 95 V, 100 Hz, 30 and 60 min) while
      monitoring the pH and temperature. After the stimulation, the suspensions were
      plated and incubated for 24 hours at 37 degrees C. Then the counts were made of
      colony forming units (CFU). Data were submitted to normality Shapiro-Wilk test
      followed by nonparametric ANOVA test and post hoc Tukey test with p < 0.05. There
      was a decrease in the CFU for the two currents, but the most effective reduction
      was in FD-B. The temperature remained constant and the pH measured alkaline at
      the negative pole and acid at the positive pole during stimulation. The
      application of FD-B and HVMP currents promoted inhibition of bacterial
      proliferation when stimulated in vitro, acting as an adjuvant resource in the
      healing process. 

PMID- 25845401
TI  - Acute generalized exanthematous pustulosis following paracetamol ingestion in a
      child.

PMID- 25845402
TI  - Effects of ethanol exposure in utero on Cajal-Retzius cells in the developing
      cortex.
AB  - BACKGROUND: Prenatal exposure to ethanol exerts teratogenic effects on the
      developing brain. Here, we tested the hypothesis that exposure to ethanol in
      utero alters the disposition of Cajal-Retzius cells that play a key role in
      orchestrating proliferation, migration, and laminar integration of cortical
      neurons in the embryonic cortex. METHODS: Pregnant Ebf2-EGFP mice, harboring EGFP
      fluorescent Cajal-Retzius cells, were subjected to a 2% w/w ethanol consumption
      regimen starting at neural tube closure and lasting throughout gestation. Genesis
      of Cajal-Retzius cells was assessed by means of 5-bromo-2-deoxyuridine (BrdU)
      immunofluorescence at embryonic day 12.5, their counts and distribution were
      determined between postnatal day (P)0 and P4, patch clamp electrophysiology was
      performed between P2 and P3 to analyze GABA-mediated synaptic activity, and open
      field behavioral testing was conducted in P45-P50 adolescents. RESULTS: In Ebf2
      EGFP embryos exposed to ethanol in utero, we found increased BrdU labeling and
      expanded distribution of Cajal-Retzius cells in the cortical hem, pointing to
      increased genesis and proliferation. Postnatally, we found an increase in Cajal
      Retzius cell number in cortical layer I. In addition, they displayed altered
      patterning of spontaneous GABA-mediated synaptic barrages and enhanced GABA
      mediated synaptic activity, suggesting enhanced GABAergic tone. CONCLUSIONS:
      These findings, together, underscore that Cajal-Retzius cells contribute to the
      ethanol-induced aberration of cortical development and abnormal GABAergic
      neurotransmission at the impactful time when intracortical circuits form.

PMID- 25845403
TI  - Advances in surgical treatment of chronic pancreatitis.
AB  - The incidence of chronic pancreatitis (CP) is between 2 and 200 per 100,000
      persons and shows an increasing trend year by year. India has the highest
      incidence of CP in the world at approximately 114 to 200 per 100,000 persons. The
      incidence of CP in China is approximately 13 per 100,000 persons. The aim of this
      review is to assist surgeons in managing patients with CP in surgical treatment.
      We conducted a PubMed search for "chronic pancreatitis" and "surgical treatment"
      and reviewed relevant articles. On the basis of our review of the literature, we
      found that CP cannot be completely cured. The purpose of surgical therapy for CP
      is to relieve symptoms, especially pain; to improve the patient's quality of
      life; and to treat complications. Decompression (drainage), resection,
      neuroablation and decompression combined with resection are commonly used methods
      for the surgical treatment of CP. Before developing a surgical regimen, surgeons
      should comprehensively evaluate the patient's clinical manifestations, auxiliary
      examination results and medical history to develop an individualized surgical
      treatment regimen. 

PMID- 25845404
TI  - Bovine Circadian Locomotor Output Cycles Kaput (CLOCK) and Clusterin (CLU) mRNA
      Quantitation in Ejaculated Crossbred Bull Spermatozoa.
AB  - Mammalian circadian locomotor output cycles kaput (CLOCK) gene encodes a
      transcription factor that affects both the persistence and the period of
      circadian rhythms. Earlier reports suggested that CLOCK gene might be associated
      with male infertility in human. Present investigation, for the first time,
      reports that CLOCK gene expresses differentially between good and poor quality
      crossbred bull semen. The relative expression of CLOCK was significantly (p <
      0.05) higher among good quality bull semen than motility-impaired ones.
      Clusterins (CLU) are series of genes associated with a variety of physiological
      activities including spermatogenesis, apoptosis and degenerative disease
      conditions. In the present context, we also investigated that the expression of
      CLU gene was significantly (p < 0.05) higher among motility-impaired crossbred
      bull semen compared to the good quality one. 

PMID- 25845405
TI  - 1064 nm Q-switched Nd:YAG laser for the treatment of Argyria: a systematic
      review.
AB  - Argyria is a benign skin disease characterized by blue to slate-grey
      discoloration that is caused by deposition of silver granules in the skin and/or
      mucus membranes as a result of long-term ingestion of ionized silver solutions or
      exposure to airborne silver particles. The skin discoloration can be generalized
      or localized and is exacerbated by sunlight. The skin discoloration is usually
      permanent, and until recently, there has been no effective treatment for argyria.
      Over the past 6 years, a number of case reports and one case series have
      described cases of argyria that were successfully treated with a 1064 nm Q
      switched (QS) neodymium-doped yttrium aluminium garnet (Nd:YAG) laser; however, a
      review of these studies has never been reported in the dermatologic literature.
      To review the use of the 1064 nm QS Nd:YAG laser for the treatment of argyria. A
      search of the National Library of Medicine's PubMed Database and the SCOPUS
      Database was performed to find articles that detailed the treatment of argyria
      with 1064 nm QS Nd:YAG laser. Six articles were selected for inclusion in this
      review. Each article was reviewed and summarized in a table. A 1064 nm QS Nd:YAG
      laser offers a novel and effective treatment for argyria. A systematic review of
      the dermatologic literature revealed a limited number of case reports and case
      series using this treatment. However, the results gleaned by the authors from the
      literature review provide important information to the clinician. For patients
      with argyria, a single pass of the 1064 nm QS Nd:YAG laser offers immediate,
      effective and sustained pigment clearing without any long-term adverse effects. 

PMID- 25845406
TI  - Efficacy and safety of non-hormonal remedies for vaginal dryness: open,
      prospective, randomized trial.
AB  - OBJECTIVES: To prove non-inferiority of the first non-hormonal vaginal cream in
      Germany, Vagisan((r)) Moisturising Cream (CREAM), compared to a non-hormonal
      vaginal gel (GEL) for vulvovaginal atrophy (VVA) symptom relief. METHOD: This was
      a 12-week multicenter, open-label, prospective, randomized, two-period, cross
      over phase-III trial. The primary endpoint was the cumulative VVA subjective
      symptom score of the respective treatment period. Secondary endpoints were
      assessment of single VVA subjective and objective symptoms, VVA objective symptom
      score, vaginal pH, safety parameters, overall assessment of efficacy,
      tolerability and evaluation of product properties. In total, 117 women were
      randomly allocated to either one of the two treatments, each administered for 4
      weeks; 92 women were included in the per-protocol analysis (primary analysis).
      The main outcome measure was cumulative VVA subjective symptom score. RESULTS:
      Regarding VVA symptom relief, results confirmed non-inferiority of CREAM compared
      to GEL and even indicated superiority of CREAM. Frequency and intensity of
      subjective symptoms and objective findings were clearly reduced, with CREAM
      showing better results compared to GEL. Mean VVA objective symptom score
      significantly decreased; improvement was significantly greater with CREAM.
      Vaginal pH decreased only following CREAM treatment. Tolerability was superior
      for CREAM: burning and itching, mostly rated as mild, occurred markedly less
      often with CREAM than with GEL. Overall satisfaction with treatment efficacy,
      tolerability and most product properties were rated significantly superior for
      CREAM. CONCLUSIONS: Subjective and objective VVA symptoms were reliably and
      safely reduced by both non-hormonal topical products. However, efficacy and
      tolerability of CREAM were shown to be superior to GEL.

PMID- 25845408
TI  - Blending qualitative and quantitative research methods to optimize patient
      reported outcome measures (PROMs).

PMID- 25845407
TI  - HIV and HCV Medications in End-Stage Renal Disease.
AB  - Human immunodeficiency virus (HIV) infection and hepatitis C virus (HCV)
      infection affect populations worldwide. With the availability of over 35 Food and
      Drug Administration approved medications for treatment of HIV, the morbidity and
      mortality associated with HIV has greatly improved. On the other hand, treatment
      options for HCV have been limited until very recently. While the use of protease
      inhibitors (such as boceprevir and telaprevir) has become standard of care for
      treatment of hepatitis C in the general population, data for individuals with
      impaired kidney function, particularly those on dialysis, are extremely limited.
      Use of medications in dialysis patients can be challenging given the dose
      adjustments that must be made for renally cleared molecules, and potentially
      increased impact of adverse effects such as anemia. Recommendations for dosing of
      marketed therapies for HIV and HCV are reviewed. 

PMID- 25845409
TI  - Cumulative risk disparities in children's neurocognitive functioning: a
      developmental cascade model.
AB  - The current longitudinal study examined the role of cumulative social risk on
      children's theory of mind (ToM) and executive functioning (EF) across early
      development. Further, we also tested a cascade model of development in which
      children's social cognition at 18 months was hypothesized to predict ToM and EF
      at age 4.5 through intermediary language skills at age 3. We then examined
      whether this developmental mechanism varied as a function of social risk status.
      Participants were 501 children recruited when they were newborns, at which point
      eight psychosocial risk factors were assessed and combined into a metric of
      cumulative social disadvantage. Families were followed up at 18 months, at which
      point four social-cognitive skills were assessed using developmentally sensitive
      tasks: joint attention, empathy, cooperation, and self-recognition. Language was
      measured at age 3 using a standardized measure of receptive vocabulary. At age 3
      and 4.5, EF and ToM were measured using previously validated tasks. Results
      showed that there were notable cumulative risk disparities in overall
      neurocognitive skill development, and these effects became more differentiated
      over time. Support was also found for a developmental mechanism wherein the
      effect of social cognition at 18 months on ToM and EF in the preschool period
      operated specifically through children's receptive language ability at age 3.
      This pathway functioned similarly for children with both low- and high-risk
      backgrounds. These results extend previous findings by documenting the role of
      cumulative social disadvantage on children's neurocognition and the pathways that
      link key neurocognitive abilities across early development.

PMID- 25845410
TI  - Differential regulation of toxoflavin production and its role in the enhanced
      virulence of Burkholderia gladioli.
AB  - Burkholderia gladioli is a causal agent of bacterial panicle blight and
      sheath/grain browning in rice in many countries. Many strains produce the yellow
      pigment toxoflavin, which is highly toxic to plants, fungi, animals and
      microorganisms. Although there have been several studies on the toxoflavin
      biosynthesis system of B. glumae, it is still unclear how B. gladioli activates
      toxoflavin biosynthesis. In this study, we explored the genomic organization of
      the toxoflavin system of B. gladioli and its biological functions using
      comparative genomic analysis between toxoflavin-producing strains (B. glumae BGR1
      and B. gladioli BSR3) and a strain not producing toxoflavin (B. gladioli
      KACC11889). The latter exhibits normal physiological characteristics similar to
      other B. gladioli strains. Burkholderia gladioli KACC11889 possesses all the
      genes involved in toxoflavin biosynthesis, but lacks the quorum-sensing (QS)
      system that functions as an on/off switch for toxoflavin biosynthesis. These data
      suggest that B. gladioli has evolved to use the QS signalling cascade of
      toxoflavin production (TofI/TofR of QS -> ToxJ or ToxR -> tox operons) similar to
      that in B. glumae. However, some strains may have evolved to eliminate toxoflavin
      production through deletion of the QS genes. In addition, we demonstrate that the
      toxoflavin biosynthetic system enhances the virulence of B. gladioli. These
      findings provide another line of evidence supporting the differential regulation
      of the toxoflavin system in Burkholderia strains. 

PMID- 25845411
TI  - Identification and functional expression of genes encoding flavonoid O- and C
      glycosidases in intestinal bacteria.
AB  - Gut bacteria play a crucial role in the metabolism of dietary flavonoids and
      thereby influence the bioactivity of these compounds in the host. The intestinal
      Lachnospiraceae strain CG19-1 and Eubacterium cellulosolvens are able to
      deglycosylate C- and O-coupled flavonoid glucosides. Growth of strain CG19-1 in
      the presence of the isoflavone C-glucoside puerarin (daidzein 8-C-glucoside) led
      to the induction of two proteins (DfgC, DfgD). Heterologous expression of the
      encoding genes (dfgC, dfgD) in Escherichia coli revealed no C-deglycosylating
      activity in the resulting cell extracts but cleavage of flavonoid O-glucosides
      such as daidzin (daidzein 7-O-glucoside). The recombinant DfgC and DfgD proteins
      were purified and characterized with respect to their quaternary structure,
      substrate and cofactor specificity. The products of the corresponding genes
      (dfgC, dfgD) from E. cellulosolvens also catalysed the O-deglycosylation of
      daidzin following their expression in E. coli. In combination with three
      recombinant proteins encoded by adjacent genes in E. cellulosolvens (dfgA, dfgB,
      dfgE), DfgC and DfgD from E. cellulosolvens catalysed the deglycosylation of the
      flavone C-glucosides homoorientin (luteolin 6-C-glucoside) and isovitexin
      (apigenin 6-C-glucoside). Even intact cells of E. coli expressing the five E.
      cellulosolvens genes cleaved these flavone C-glucosides and, also, flavonoid O
      glucosides to the corresponding aglycones.

PMID- 25845413
TI  - Individual prevention courses for occupational skin diseases: changes in and
      relationships between proximal and distal outcomes.
AB  - BACKGROUND: To treat people with occupational contact dermatitis, the German
      Accident Prevention and Insurance Association in the Health and Welfare Services
      offers 2-day individual prevention (IP) seminars. OBJECTIVES: We investigated
      whether there are short-term and medium-term changes in proximal (e.g. behaviour)
      and distal (e.g. symptoms) outcomes after an IP seminar, whether changes in
      proximal outcomes are associated with changes in distal outcomes, and whether
      subgroups can be identified that benefit in particular.
      PATIENTS/MATERIALS/METHODS: In a prospective study, 502 participants of 85 IP
      courses completed the health education impact questionnaire (heiQTM) and skin
      symptom questionnaire (Skindex-29) at the start of the course, immediately
      thereafter, and after 6 months. Change was assessed according to standardized
      effect size. Regression techniques were used to analyse associations between
      proximal and distal outcomes. RESULTS: After 6 months, participants showed
      improved self-management skills and preventive behaviour, and less fear of job
      loss, disease-related symptoms, and emotional distress. Significant associations
      between proximal and distal outcomes were found. Participants who felt more
      limited by their skin disease showed greater effects. CONCLUSIONS: The results
      are consistent with the assumption that IP courses provide a range of benefits
      for people with occupational contact dermatitis. Changes in distal outcomes may
      be influenced by changes in proximal outcomes.

PMID- 25845412
TI  - Safety of vitamin K antagonist treatment for splanchnic vein thrombosis: a
      multicenter cohort study.
AB  - BACKGROUND: The treatment of splanchnic vein thrombosis (SVT) is challenging, due
      to the increased risk of bleeding and potentially life-threatening complications.
      Current recommendations are based on evidence from the treatment of venous
      thrombosis in usual sites, but small observational studies in SVT population
      suggest that the bleeding risk may offset the benefit of anticoagulant treatment
      in this setting. The aim of this study was to evaluate the safety of vitamin K
      antagonists (VKAs) in SVT patients. METHODS: We retrospectively included SVT
      patients treated with VKAs followed by 37 Italian anticoagulation clinics, until
      June 2013. The primary outcome was the incidence of major bleeding (MB),
      according to the ISTH definition, during VKA treatment. Vascular events,
      including both arterial and venous thrombosis, and mortality were also
      documented. RESULTS: Three hundred and seventy-five patients were included
      (median age 53 years; 54.7% males). During a median VKA treatment duration of
      1.98 years, 15 MB events occurred, corresponding to an incidence rate of 1.24
      (95% confidence interval [CI], 0.75-2.06) per 100 patient-years. Gastrointestinal
      bleeding represented 40% of all MB events. At multivariate analysis, the presence
      of esophageal varices emerged as independent predictor of MB (hazard ratio 5.4;
      95% CI, 1.4-21.1). The incidence rate of vascular events on treatment was 1.37
      (95% CI, 0.84-2.23) per 100 patient-years and the mortality rate was 0.83 (95%
      CI, 0.44-1.54) per 100 patient-years. CONCLUSIONS: Selected SVT patients followed
      by anticoagulation clinics for the management of VKA treatment show a low rate of
      major bleeding and vascular events.

PMID- 25845414
TI  - Adalimumab-Induced Cutaneous Lupus Erythematosus in a 16-Year-Old Girl with
      Juvenile Idiopathic Arthritis.
AB  - Tumor necrosis factor alpha (TNF-alpha) antagonists are used in the treatment of
      numerous autoimmune conditions. Adalimumab is the first monoclonal antibody to
      TNF-alpha and is used to treat juvenile idiopathic arthritis. A growing body of
      literature associates anti-TNF-alpha therapies with several adverse dermatologic
      manifestations, including drug-induced lupus erythematosus (LE). We describe a
      case of cutaneous LE in a 16-year-old girl treated with adalimumab for juvenile
      idiopathic arthritis. The temporal association between her presenting symptoms
      and adalimumab initiation and gradual improvement after stopping biologic therapy
      suggest adalimumab-induced cutaneous LE. With increasing use of anti-TNF
      therapies in children, the potential for drug-induced LE should not be
      overlooked. 

PMID- 25845415
TI  - Reply on recommendations for postpartum hemorrhage in women who decline blood
      transfusion.

PMID- 25845416
TI  - The Role of Attachment Style in Predicting Repetition of Adolescent Self-Harm: A
      Longitudinal Study.
AB  - This study investigated whether insecure attachment is associated with poorer
      outcomes at 6-month follow-up in adolescents who self-harm. At baseline the Child
      Attachment Interview was administered to 52 adolescents (13-17 years) referred to
      specialist child and adolescent mental health services and with a recent history
      of self-harm. Participants also completed self-report measures of self-harm, peer
      attachment, anxiety, and depression and were administered the means end problem
      solving task. Self-harm behavior and problem-solving skills were assessed again
      at 6-month follow-up. At baseline, 14 (27%) were securely attached to their
      mothers. In the 49 (94%) adolescents followed-up, those with insecure maternal
      attachment and insecure peer attachment were more likely to have repeated self
      harm. In addition, securely attached adolescents showed greater improvement in
      problem-solving skills. These findings indicate that secure maternal and peer
      attachments may help recovery from self-harm, possibly by supporting the
      acquisition of problem-solving skills, and highlights the importance of social
      connections and attachments for youth with a history of self-harm. 

PMID- 25845417
TI  - The association between the serum levels of uric acid and alanine
      aminotransferase in a population-based cohort.
AB  - BACKGROUND & AIMS: Elevated serum uric acid levels reflect and also cause both
      oxidative stress and insulin resistance and are frequently observed in patients
      with the metabolic syndrome. A strong association exists between the metabolic
      syndrome and non-alcoholic fatty liver disease (NAFLD). Therefore, we aimed to
      test the association between uric acid and elevated alanine aminotransferase
      (ALT), as a surrogate for NAFLD, using real-world data. METHODS: Data used for
      the cross-sectional study were obtained from Maccabi Healthcare System, a 2
      million member health maintenance organization in Israel. The population
      consisted of individuals aged 20-60 years who underwent blood tests for ALT and
      uric acid between 1997 and 2012. Individuals with secondary liver disease,
      celiac, and inflammatory bowel-disease were excluded. Subgroup analysis was
      performed in subjects who were given the diagnosis of fatty liver in their
      medical records (n = 2628). RESULTS: The study population included 82,608 people
      (32.5% men, mean age 43.91 +/- 10.15 years). There was a significant positive
      dose-response association between serum uric acid levels and the rate of elevated
      serum ALT (P for trend <0.001). In multivariable model, controlling for potential
      confounders, the association between uric acid and elevated ALT persisted (OR =
      2.10, 95% CI 1.93-2.29, for the fourth quartile vs. the first). This association
      was maintained in all categories of gender and BMI. Similar results were observed
      among patients diagnosed with fatty liver (OR = 1.77, 1.22-2.57). CONCLUSIONS:
      Serum uric acid is independently associated with elevated ALT, as a surrogate for
      NAFLD, and thus may serve as a serum marker for liver damage and should be
      further investigated as a risk factor for NAFLD.

PMID- 25845419
TI  - Pulsed intravenous immunoglobulin therapy in refractory ulcerated livedoid
      vasculopathy: seven cases and a literature review.
AB  - Livedoid vasculopathy (LV) is a thrombotic vasculopathy of the skin of unknown
      origin. No treatment has been validated in this indication, but case reports
      demonstrated successful use of intravenous immunoglobulins (IVIg) in LV. We
      assessed the efficacy and tolerability of 2 g/kg IVIg therapy every month for 2~3
      cycles in patients with refractory LV. We analyzed the efficacy, side effects and
      recurrence after long-term follow-up (51.9 +/- 14.0 months) in seven patients
      with LV treated with 2 g/kg of IVIg. Mean clinical score of sum of erythema,
      ulceration and pain index (each: 0-3) was 5.7 +/- 0.9 before the therapy and
      significantly lower after therapy (1.1 +/- 0.5) (p = 0.001). Even after just one
      cycle of IVIg, the score decreased significantly from 5.7 +/- 0.9 to 3.7 +/- 0.9
      (p = 0.002), especially the pain score. In one patient, LV has not recurred for
      over 7 years; six patients experienced recurrence after a mean of 12.7 +/- 2.8
      months. Out of the six patients, two patients were re-administered IVIg whereas
      the others were well controlled by conventional therapy. We propose that IVIg is
      a rapid, effective, and safe therapeutic option in LV refractory to other
      treatment modalities.

PMID- 25845418
TI  - Increased lymphocyte apoptosis in mouse models of colitis upon ABT-737 treatment
      is dependent upon BIM expression.
AB  - Exaggerated activation of lymphocytes contributes to the pathogenesis of
      inflammatory bowel disease (IBD). Medical therapies are linked to the BCL-2
      family-mediated apoptosis. Imbalance in BCL-2 family proteins may cause failure
      in therapeutic responses. We investigated the role of BCL-2 inhibitor ABT-737 for
      lymphocyte apoptosis in mice under inflammatory conditions. B.6129P2-interleukin
      (IL)-10(tm1Cgn) /J (IL-10(-/-) ) weighing 25-30 g with ongoing colitis were used.
      Fifty mg/kg/day ABT-737 was injected intraperitoneally (i.p.). Haematological
      analyses were performed with an ADVIA 2120 flow cytometer and mass cytometry with
      a CyTOF 2. Following i.p. administration, ABT-737 was detected in both
      spontaneous and acute colitis in peripheral blood (PBL) and colon tissue.
      Treatment led to lymphopenia. CD4(+) CD44(+) CD62L(+) central memory and CD8(+) ,
      CD44(+) CD62L(-) central memory T cells were decreased in PBL upon ABT-737
      compared to vehicle-receiving controls. Increased apoptosis upon ABT-737 was
      determined in blood lymphocytes, splenocytes and Peyer's patches and was
      accompanied by a decrease in TNF and IL-1B. ABT-737 positively altered the
      colonic mucosa and ameliorated inflammation, as shown by colonoscopy, histology
      and colon length. A decreased BIM/BCL-2 ratio or absence of BIM in both Bim(-)
      (/) (-) and Il10(-) (/) (-) * Bim(-) (/) (-) impeded the protective effect of ABT
      737. The BIM/BCL-2 ratio decreased with age and during the course of treatment.
      Thus, long-term treatment resulted in adapted TNF levels and macroscopic mucosal
      damage. ABT-737 was efficacious in diminishing lymphocytes and ameliorating
      colitis in a BIM-dependent manner. Regulation of inappropriate survival of
      lymphocytes by ABT-737 may provide a therapeutic strategy in IBD. 

PMID- 25845420
TI  - The relationship between renal volume and histology in obese and nonobese kidney
      donors.
AB  - BACKGROUND: Obesity and related kidney diseases have become a global epidemic
      problem. However, the underlying pathogenesis of obesity-related renal diseases
      has not been clearly understood. In this study, we explored the link between
      renal volume (RV) determined by computed tomography (CT) and renal histology
      together with functional parameters in an obese population. MATERIALS AND
      METHODS: Eighty-two kidney donors who underwent CT for the measurement of kidney
      volume and zero-hour renal biopsy for renal histology were included in this cross
      sectional study. Protein creatinine clearance and eGFR were evaluated in 24-h
      urine specimens as indicators of renal function. RESULTS: Mean body mass index
      (BMI) was 28 +/- 4.2 kg/m(2); 32.9% (n = 27) were obese. Mean RV was 196 +/- 36
      cm(3). RV was positively correlated with BMI, body surface area and creatinine
      clearance and negatively with HDL-cholesterol in the whole population. Renal
      function parameters of obese subjects were better, and their renal volumes were
      higher compared with the nonobese subjects. In obese subjects, corrected RV was
      positively correlated with glomerular filtration rate (r = 0.46, P = 0.01) and
      negatively with sclerotic glomeruli (r = -0.38, P = 0.04) and chronicity index (r
      = -0.43, P = 0.02). In adjusted ordinal logistic regression analysis, corrected
      RV was significantly associated with chronicity index (OR: 0.96; P = 0.01).
      CONCLUSIONS: In obese cases, decreased RV determined by CT is associated with
      worse renal histology. In this population, kidney imaging techniques may provide
      important clues about renal survival.

PMID- 25845421
TI  - Design, synthesis, and biological evaluation of novel peptide Gly(3) -MC62
      analogues as potential antidiabetic agents.
AB  - Two series of conformationally constrained analogues from Gly(3) -MC62 were
      designed by scanning the residues Lys(1) , Thr(2) , Met(4) , Lys(5) , Met(7,) and
      Ala(8) with an i-(i + 2) lactam bridge consisting of a Glutamic acid-xaa-lysine
      (Glu-Xaa-Lys) scaffold and a diproline fragment. They were synthesized and
      evaluated for their antihyperglycemic effects. Through screening in normal and
      mice with diabetes mellitus, peptides II-5, III-3, III-4, and III-5 showed
      significant improvement in antihyperglycemic and antioxidative activities
      compared with Gly(3) -MC62, especially the compound III-4. The primary mechanism
      of the compounds (II-5, III-3, III-4, and III-5) underlying this effect is the
      islet beta-cells against oxidative damage induced by STZ, and III-4-treated mice
      showed considerable improvement in the preservation of beta cells in the
      pancreatic islets of DM mice. These data suggested that III-4 could be candidate
      for the future treatment of diabetes mellitus. 

PMID- 25845422
TI  - Bioinspired synthesis of fluorescent calcium carbonate/carbon dot hybrid
      composites.
AB  - Herein, we report a novel method to synthesise fluorescent calcium
      carbonate/carbon dots (CaCO3/CDs) by simply mixing CaCl2 and Na2CO3 solutions in
      the presence of CDs. There are two roles of CDs in this easy and cost-effective
      biomimetic strategy, that is as the template to direct the formation and assembly
      of calcite nanocrystals into hierarchical spheres with diameters in the range of
      200-300 nm and simultaneously as the phosphor to enable the CaCO3 to emit blue
      fluorescence under UV (365 nm) irradiation with a quantum yield of 56.2%. The
      CaCO3/CD hybrid composites possessing unique fluorescence properties are
      potentially useful in various applications. 

PMID- 25845423
TI  - Semiconductor-enhanced Raman scattering for highly robust SERS sensing: the case
      of phosphate analysis.
AB  - Quantitative analysis of phosphate anions was achieved by measurement of "turn
      off" SERS based on the first-layer effect of a chemical mechanism. More
      importantly, our results demonstrate that it is possible, by means of
      semiconductor-enhanced Raman scattering, to enhance the SERS sensing performance
      including stability and reproducibility. 

PMID- 25845424
TI  - Highly efficient and stable photocatalytic reduction of CO2 to CH4 over Ru loaded
      NaTaO3.
AB  - An efficient and stable photocatalytic activity was obtained over NaTaO3 by
      introducing an electron donor (H2) into the CO2 reduction process with water.
      Ru/NaTaO3 demonstrated the best activity (CH4 51.8 MUmol h(-1) g(-1)) and product
      selectivity in converting CO2 to CH4. 

PMID- 25845426
TI  - Equilibration Kinetics and Chemical Diffusion of Indium-Doped TiO2.
AB  - The present work reports the gas/solid equilibration kinetics for In-doped TiO2
      (0.4 atom % In) at elevated temperatures (1023-1273 K) in the gas phase of
      controlled oxygen activity [10(-13) Pa < p(O2) < 10(5) Pa]. Thus, the determined
      chemical diffusion coefficient is considered in terms of a microdiffusion
      coefficient that is reflective of the transport kinetics within very narrow
      ranges of oxygen activities. In analogy to pure TiO2, the chemical diffusion
      coefficient for In-doped TiO2 exhibits a maximum at the n-p transition point. The
      activation energy of the chemical diffusion exhibits a decrease with temperature
      from 200 kJ/mol at 1023 K to an insignificant value at 1273 K. This effect is
      reflective of a segregation-induced electrical potential barrier blocking the
      transport of defects. The absolute value of the chemical diffusion coefficient
      for In-doped TiO2 is larger from that of pure TiO2 by a factor of approximately
      10. The effect of indium on the diffusion rate is considered in terms of the
      associated concentration of oxygen vacancies, which are formed in order to
      satisfy the charge neutrality for In-doped TiO2. 

PMID- 25845425
TI  - Redox-responsive polycation-functionalized cotton cellulose nanocrystals for
      effective cancer treatment.
AB  - Carbon nanotubes have excellent penetrability and encapsulation efficiency in the
      fields of drug and gene delivery. Because of their excellent physicochemical
      properties, biocompatible rodlike cellulose nanocrystals (CNCs) were reportedly
      expected to replace carbon nanotubes. In this work, CNCs from natural cotton wool
      were functionalized with disulfide bond-linked poly(2-(dimethylamino)ethyl
      methacrylate) (PDMAEMA) brushes for effective biomedical applications. A range of
      CNC-graft-PDMAEMA vectors (termed as CNC-SS-PDs) with various molecular weights
      of PDMAEMA were synthesized. Under reducible conditions, PDMAEMA chains can be
      easily cleaved from CNCs. The gene condensation ability, reduction sensitivity,
      cytotoxicity, gene transfection, and in vivo antitumor activities of CNC-SS-PDs
      were investigated in detail. The CNC-SS-PDs exhibited good transfection
      efficiencies and low cytotoxicities. The needlelike shape of CNCs had an
      important effect on enhancing transfection efficiency. The antitumor effect of
      CNC-SS-PDs was evaluated by a suicide gene/prodrug system (cytosine deaminase/5
      fluorocytosine, CD/5-FC) in vitro and in vivo. This research demonstrates that
      the functionalization of CNCs with redox-responsive polycations is an effective
      method for developing novel gene delivery systems. 

PMID- 25845427
TI  - Epithelial-to-mesenchymal transition in paired human primary and recurrent
      glioblastomas.
AB  - Patients with highly malignant glioblastomas have a short median survival time
      mainly due to aggressive relapses after therapeutic treatment. Beside others,
      they achieve their progressive character via epithelial-to-mesenchymal transition
      (EMT). However, comprehensive investigations on EMT in paired primary-recurrent
      glioblastoma pairs are presently not available. Thus, in our present study we
      examined the expression profile of different EMT-markers in 17 matched primary
      and recurrent glioblastomas by qPCR and double-immunofluorescence stainings to
      identify EMT marker expressing cell types. Additionally, we analyzed the
      influence of temozolomide on EMT marker expression in vitro. In comparison to
      primary tumors, expression of beta-catenin (p<0.05), Snail1 (p<0.05), Snail2/Slug
      (p<0.05), biglycan (p<0.05) and Twist1 (p<0.01) was downregulated in recurrence
      whereas L1CAM showed upregulation (p<0.05; qPCR). Expression of desmoplakin,
      vimentin, fibronectin and TGF-beta1 with its receptors TGF-betaR1 and TGF-betaR2
      was almost unchanged. Comparing each individual pair, five different 'EMT groups'
      within our glioblastoma collective were identified according to the regulation of
      mRNA expression of GFAP, desmoplakin, Snail1, Snail2, Twist1 and vimentin.
      Additionally, double-stainings of EMT markers in combination with cell specific
      markers (glial fibrillary acidic protein, CD11b, von Willebrand factor) revealed
      that EMT markers were expressed in a complex pattern with all three cellular
      types as possible sources. Temozolomide treatment significantly induced mRNA
      expression of nearly all investigated EMT markers in T98G glioma cells. Thus, EMT
      seems to be involved in glioma progression in a complex way requiring an
      individualized analysis, and is influenced by commonly used therapeutic options
      in glioma therapy.

PMID- 25845428
TI  - Spatial neglect in a patient with logopenic progressive aphasia.
AB  - Spatial neglect and extinction are induced by posterior superior temporal and
      inferior parietal dysfunction. In patients with logopenic progressive aphasia
      (LPA) these structures are often degenerated, but there are no reports of these
      disorders being associated. A 53-year-old man with the signs of LPA revealed
      right-sided spatial neglect on line bisection and drawing tests as well as
      multimodal extinction. MRI showed left hemispheric posterior temporoparietal
      atrophy. Since injury to the core structures for these aphasic and attentional
      syndromes overlaps, patients with LPA should be screened for spatial neglect and
      extinction. 

PMID- 25845430
TI  - Do All Patients Require Prophylactic Drainage After Gastrectomy for Gastric
      Cancer? The Experience of a High-Volume Center.
AB  - BACKGROUND: Although our previous randomized controlled trial showed that there
      was no difference in postoperative complications after gastric cancer surgery
      between patients with and without a prophylactic drains (PDs), PDs are commonly
      used by most surgeons and at most institutions. However, these results have not
      yet been validated elsewhere. The purpose of this study was to analyze the
      incidence, characteristics, and risk factors for a postoperative percutaneous
      catheter drainage (PCD) procedure after gastric cancer surgery when PDs were not
      used. METHODS: We reviewed data from 1989 patients who underwent gastrectomy with
      lymphadenectomy for gastric cancer with curative intent from January 2012 to
      December 2013. RESULTS: The incidence of PCD in the abdomen was 1.8 % (22/1249)
      and 9.1 % (67/740) in patients with and without PD, respectively. In the without
      PD group, age [odds ratio (OR) 1.032; p = 0.013], male gender (OR for female
      0.38; p = 0.005), open surgery (OR for minimally invasive surgery 0.16; p =
      0.013), and longer operative time (OR 1.01; p < 0.001) were independent risk
      factors for postoperative PCD in the abdomen. In the without-PD group, no
      microbes were detected in the peritoneal fluid obtained by PCD in 72.1 % (44/61)
      of patients who underwent PCD, and the most commonly identified organisms were
      Escherichia coli and Candida albicans. CONCLUSION: Not using a PD increased the
      risk of PCD postoperatively, but no microbes in peritoneal fluid were detected in
      the most patients. Selective use of PD in patients during gastric cancer surgery
      may be possible using our risk factor analysis.

PMID- 25845431
TI  - Nodular Regenerative Hyperplasia in Patients Undergoing Liver Resection for
      Colorectal Metastases After Chemotherapy: Risk Factors, Preoperative Assessment
      and Clinical Impact.
AB  - BACKGROUND: Nodular regenerative hyperplasia (NRH) is a severe form of
      chemotherapy-related liver injury (CALI) that may worsen the short-term outcome
      of liver resection (LR) for colorectal metastases (CRLM). The present study aimed
      to clarify the incidence, risk factors, preoperative assessment, and clinical
      impact of NRH. METHODS: Overall, 406 patients undergoing 478 LRs for CRLM after
      chemotherapy between 2000 and 2012 were studied. All resection specimens were
      reviewed. After Gomori staining, NRH was graded according to the Wanless score.
      RESULTS: NRH was diagnosed in 87 (18.2 %) patients, grades 2-3 in 14 (2.9 %)
      patients. At multivariate analysis, the prevalence of NRH was increased after
      oxaliplatin administration (21.4 vs. 8.4 %; p = 0.003), and reduced by the
      addition of bevacizumab (11.7 vs. 19.8 %; p = 0.020). Two parameters predicted
      the presence of NRH: the APRI score (AST to platelet ratio index: 25.5 % if >0.36
      vs. 9.8 % if <=0.36; p = 0.004), and the platelet count (63.6 % if <100 *
      10(3)/mm(3) vs. 25.3 % if 100-200 * 10(3)/mm(3) vs. 11.9 % if >200 * 10(3)/mm(3);
      p = 0.032). Ninety-day mortality and liver failure rates were 0.6 and 3.6 %. NRH
      was an independent predictor of postoperative liver failure (9.2 % if present vs.
      2.3 % if not present; p = 0.021). In patients with grades 2-3 NRH, the rate of
      liver failure was 14.3 %, 25.0 % after major hepatectomy. No other forms of CALI
      impacted short-term outcomes. CONCLUSIONS: NRH was the most relevant form of
      CALI, increasing the risk of postoperative liver failure. Oxaliplatin increased
      the incidence of NRH, while bevacizumab decreased it. The APRI score and platelet
      count were useful tools for predicting NRH.

PMID- 25845433
TI  - Optimized generation of survivin-specific cytotoxic T lymphocytes against lung
      cancer.
AB  - Cancer immunotherapy based on dendritic cells (DCs) that target survivin is a
      promising strategy with potential clinical applications. However, the translation
      of survivin-specific cytotoxic T-lymphocyte (CTL) immunotherapy into the clinical
      setting has numerous challenges, including the low efficiency of the treatment.
      The present study aimed to improve the efficiency of the treatment, and found
      that treatment with interleukin 4 (IL-4)/granulocyte macrophage colony
      stimulating factor (GM-CSF) and a combination of proinflammatory cytokines
      significantly increased the antigen-presenting and -capture abilities of DCs that
      expressed exogenous survivin. Furthermore, lipopolysaccharide (LPS) stimulation
      enhanced the DC response to subsequent T-cell signals and the extent of T-cell
      activation. In addition, the efficiency of surviving-specific CTLs was examined,
      and high cytotoxicity against surviving-expressing A549 lung cancer cells was
      observed. However, the cytotoxicity of CTLs was significantly reduced in A549
      cells with silenced survivin expression. The present study provides a novel
      method to optimize the generation of surviving-specific CTLs against lung cancer
      cells, which may advance the translation of surviving-specific CTL immunotherapy
      into clinical use for the treatment of cancer.

PMID- 25845434
TI  - Epigallocatechin-3-gallate inhibits nicotine-induced migration and invasion by
      the suppression of angiogenesis and epithelial-mesenchymal transition in non
      small cell lung cancer cells.
AB  - Epigallocatechin-3-gallate (EGCG), the most abundant polyphenol in green tea
      extract, has been found to have anticancer activities in various types of cancer.
      However, the underlying mechanisms are not completely clear. In the present
      study, the effects of EGCG on migration, invasion, angiogenesis and epithelial
      mesenchymal transition (EMT) induced by nicotine in A549 non-small cell lung
      cancer (NSCLC) cells were investigated, and the underlying molecular mechanisms
      were preliminarily examined. The results showed that different concentrations of
      EGCG significantly inhibited nicotine-induced migration and invasion. Moreover,
      EGCG reversed the upregulation of HIF-1alpha, vascular endothelial growth factor
      (VEGF), COX-2, p-Akt, p-ERK and vimentin protein levels and the downregulation of
      p53 and beta-catenin protein levels mediated by nicotine in A549 cells, but had
      no significant effect on their mRNA levels. Furthermore, EGCG markedly inhibited
      HIF-1alpha-dependent angiogenesis induced by nicotine in vitro and in vivo, and
      suppressed HIF-1alpha and VEGF protein expression induced by nicotine in A549
      xenografts of nude mice. Taken together, the results indicated that EGCG
      inhibited nicotine-induced angiogenesis and EMT, leading to migration and
      invasion in A549 cells. The results of the present study suggested that EGCG can
      be developed into a potential agent for the prevention and treatment of smoking
      associated NSCLC.

PMID- 25845435
TI  - Chronic inflammation in offspring of patients with type 2 diabetes and
      albuminuria.

PMID- 25845432
TI  - Expression of Tight Junction Components in Hepatocyte-Like Cells Differentiated
      from Human Embryonic Stem Cells.
AB  - Human embryonic stem cells can be differentiated in vitro into a wide variety of
      progeny cells by addition of different morphogens and growth factors. Our aim was
      to monitor the expression pattern of tight junction (TJ) components and various
      cellular markers during differentiation of stem cell lines toward the hepatic
      lineage. Human embryonic stem cell lines (HUES1, HUES9) were differentiated into
      endoderm-like cells, and further differentiated to hepatocyte-like cells. Gene
      expressions of Oct3/4, Nanog, alpha-fetoprotein, albumin, cytokeratins (CK-7, CK
      8, CK-18, CK-19), ATP-binding cassette (ABC) transporters (ABCC2, ABCC7, ABCG2),
      and various TJ components, including claudin-1, claudin-4, claudin-5, claudin-7,
      and tricellulin, as well as an extracellular matrix component, agrin were
      monitored during hepatic differentiation by real-time quantitative PCR. The
      differentiated cells exhibit epithelial morphology and functional assessments
      similar to that of hepatocytes. The expression level of stem cell marker genes
      (Oct3/4 and Nanog) significantly and gradually decreased, while liver-associated
      genes (alpha-fetoprotein, albumin) reached their highest expression at the end of
      the differentiation. The endoderm-like cells expressed claudin-1, which declined
      eventually. The expression levels of cholangiocyte markers including claudin-4,
      CK-7, CK-19, and agrin gradually increased and reached their highest level at the
      final stage of differentiation. In contrast, these cells did not express notable
      level of claudin-7, CK-8 and tricellulin. The marker set used for monitoring
      differentiation revealed both hepatocyte and cholangiocyte characteristics of the
      differentiated cells at the final stage. This is the first report describing the
      expression level changes of various TJ components, and underlining their
      importance in hepatic differentiation.

PMID- 25845437
TI  - Erratum to: High-resolution color-Doppler ultrasound for the study of skin
      growths.

PMID- 25845436
TI  - Behavioral effects of phencyclidine on nicotine self-administration and
      reinstatement in the presence or absence of a visual stimulus in rats.
AB  - RATIONALE: Tobacco use is a serious health problem in the USA, and this problem
      is potentiated in patients with schizophrenia. The reward system is implicated in
      schizophrenia and may contribute to the high comorbidity between nicotine use and
      schizophrenia, but very little research has been done on the topic. The reward
      enhancement effect of nicotine has been shown to be important in nicotine use,
      but there have been no studies on this effect in animal models of schizophrenia.
      OBJECTIVES: This study was designed to determine the effects of phencyclidine,
      used to model negative symptoms of schizophrenia, on self-administration of
      nicotine with or without a co-occurring sensory reinforcer [i.e., visual stimulus
      (VS)] in rats. METHODS: Phencyclidine (2.0 mg/kg) was administered before each of
      seven nicotine self-administration sessions (0.01 mg/kg/inf) after which rats (n
      = 8-9 per group) were given 7 days of extinction without phencyclidine
      pretreatment. Reinstatement using phencyclidine (2.0 mg/kg), nicotine (0.2
      mg/kg), and yohimbine (1.25 mg/kg, a pharmacological stressor) was tested after
      extinction to determine if previous exposure to phencyclidine would alter
      reinstatement of active lever pressing. RESULTS: Phencyclidine initially
      decreased nicotine self-administration but only in the groups with a concurrent
      VS. This decrease in self-administration dissipated after 5 days. During
      reinstatement, rats that had previously received phencyclidine during self
      administration with a VS were more sensitive to stress-induced reinstatement than
      any other group. CONCLUSIONS: These results show a transitory effect of
      phencyclidine on nicotine self-administration. Phencyclidine may induce a
      potential sensitivity to pharmacological stressors contributing to reinstatement
      of nicotine.

PMID- 25845438
TI  - Turkish and Moroccan Young Adults in the Netherlands: The Relationship Between
      Acculturation and Psychological Problems.
AB  - This study investigated the relationship between acculturation and psychological
      problems in Turkish and Moroccan young adults living in the Netherlands. A sample
      of 131 healthy young adults aged between 18 and 24 years old, with a Turkish or
      Moroccan background was recruited using snowball sampling. Data on acculturation,
      internalizing and externalizing problems, beliefs about psychological problems,
      attributions of psychological problems and barriers to care were collected and
      analyzed using Latent Class Analysis and multinomial logistic regression. Three
      acculturation classes were identified in moderately to highly educated, healthy
      Turkish or Moroccan young adults: integration, separation and diffusion. None of
      the participants in the sample were marginalized or assimilated. Young adults
      reporting diffuse acculturation reported more internalizing and externalizing
      problems than those who were integrated or separated. Separated young adults
      reported experiencing more practical barriers to care than integrated young
      adults. Further research with a larger sample, including young adult migrants
      using mental health services, is required to improve our understanding of
      acculturation, psychological problems and barriers to care in this population.
      Including experiences of discrimination in the model might improve our
      understanding of the relationship between different forms of acculturation and
      psychological problems. 

PMID- 25845439
TI  - The platypnea-orthodeoxia syndrome: an unusual case of dyspnea.

PMID- 25845440
TI  - Protocadherins and hypothalamic development: do they play an unappreciated role?
AB  - Normal brain development requires coordinated cell movements at precise times. It
      has long been established that cell-cell adhesion proteins of the cadherin
      superfamily are involved in the adhesion and sorting of cells during tissue
      morphogenesis. In the present review, we focus on protocadherins, which form the
      largest subfamily of the cadherin superfamily and mediate homophilic cell-cell
      adhesion in the developing brain. These molecules are highly expressed during
      neural development and the exact roles that they play are still emerging.
      Although, historically, protocadherins were considered to provide mechanical and
      chemical connections between adjacent cells, recent research suggests that they
      may also serve as molecular identity markers of neurones to help guide cell
      recognition and sorting, cell migration, outgrowth of neuronal processes, and
      synapse formation. This phenomenon of single cell diversity stems, in part, from
      the vast variation in protein structure, genomic organisation and molecular
      function of the protocadherins. Although expression profiles and genetic
      manipulations have provided evidence for the role of protocadherins in the
      developing brain, we have only begun to construct a complete understanding of
      protocadherin function. We examine our current understanding of how
      protocadherins influence brain development and discuss the possible roles for
      this large superfamily within the hypothalamus. We conclude that further research
      into these underappreciated but vitally important genes will shed insight into
      hypothalamic development and perhaps the underlying aetiology of neuroendocrine
      disorders. 

PMID- 25845441
TI  - Forensic Applicability of Femur Subtrochanteric Shape to Ancestry Assessment in
      Thai and White American Males.
AB  - Ancestry assessment from the postcranial skeleton presents a significant
      challenge to forensic anthropologists. However, metric dimensions of the femur
      subtrochanteric region are believed to distinguish between individuals of Asian
      and non-Asian descent. This study tests the discriminatory power of
      subtrochanteric shape using modern samples of 128 Thai and 77 White American
      males. Results indicate that the samples' platymeric index distributions are
      significantly different (p<=0.001), with the Thai platymeric index range
      generally lower and the White American range generally higher. While the
      application of ancestry assessment methods developed from Native American
      subtrochanteric data results in low correct classification rates for the Thai
      sample (50.8-57.8%), adapting these methods to the current samples leads to
      better classification. The Thai data may be more useful in forensic analysis than
      previously published subtrochanteric data derived from Native American samples.
      Adapting methods to include appropriate geographic and contemporaneous
      populations increases the accuracy of femur subtrochanteric ancestry methods.

PMID- 25845442
TI  - Honey dilution impact on in vitro wound healing: Normoxic and hypoxic condition.
AB  - Honey is known as a popular healing agent against tropical infections and wounds.
      However, the effects of honey dilutions on keratinocyte (HaCaT) wound healing
      under hypoxic condition is still not explored. In this study, we examined whether
      honey dilution have wound healing potential under hypoxic stress. The antioxidant
      potential and healing efficacy of honey dilution on in vitro wound of human
      epidermal keratinocyte (HaCaT cells) under hypoxia (3% O2 ), and normoxia is
      explored by nitro blue tetrazolium assay. The cell survival % quantified by MTT
      assay to select four honey dilutions like 10, 1, 0.1, and 0.01 v/v% and the
      changes in cellular function was observed microscopically. Further, the cell
      proliferation, migration, cell-cell adhesion, and relevant gene expression were
      studied by flow cytometry, migration/scratch assay, immunocytochemistry, and
      reverse transcription-polymerase chain reaction, respectively. The expression
      pattern of cardinal molecular features viz. E-cadherin, cytoskeletal protein F
      actin, p63, and hypoxia marker Hif 1alpha were examined. Honey dilution in 0.1%
      v/v combat wound healing limitations in vitro under normoxia and hypoxia (3%).
      Its wound healing potential was quantified by immunocytochemistry and real-time
      PCR for the associated molecular features that were responsible for cell
      proliferation and migration. Our data showed that honey dilution can be effective
      in hypoxic wound healing. Additionally, it reduced superoxide generation and
      supplied favorable bioambience for cell proliferation, migration, and
      differentiation during hypoxic wound healing. These findings may reveal the
      importance of honey as an alternative and cost effective therapeutic natural
      product for wound healing in hypoxic condition. 

PMID- 25845443
TI  - Discontinuation rates of menopausal hormone therapy among postmenopausal women in
      the post-WHI study era.
AB  - OBJECTIVES: Many women are reluctant to take menopausal hormone therapy (MHT) and
      discontinue the treatment within 12 months. The aim of this study was to
      investigate the persistence rates of combined MHT in the last decade, reflecting
      changes in the post-Women's Health Initiative era. METHODS: We analyzed 17 020
      patients receiving combined MHT from 2004 to 2013 using the Disease Analyzer
      database. RESULTS: After 12 months of follow-up, 44.6% and 33.5% of patients
      receiving 1 mg and 2 mg, respectively, of oral combined MHT were still on
      treatment (p < 0.0001). The persistence rate of patients receiving < 50 MUg of
      transdermal MHT was 39.1% after 1 year of treatment and presented no differences
      compared to patients receiving >= 50 MUg of transdermal MHT with a persistence
      rate of 38.2%. MHT start in the years 2007-2009 was associated with higher
      discontinuation rates (hazard ratio 1.04, p = 0.0709) than MHT start in the years
      2010-2013 (hazard ratio 0.90, p = 0.0001). CONCLUSIONS: Our results indicate that
      patients beginning their treatments in the years 2010-2013 were more treatment
      persistent than patients beginning with MHT in the early years after publication
      of the Women's Health Initiative study (2004-2009). Administration of low-dose
      oral MHT and transdermal MHT is associated with increased persistency compared to
      higher doses of oral MHT.

PMID- 25845444
TI  - Convergence of theories of alcohol administration postanabolic stimulation on
      mTOR signaling: lessons for exercise regimen.

PMID- 25845445
TI  - A multinational study to compare prevalence of atopic dermatitis in the first
      year of life.
AB  - BACKGROUND: Atopic dermatitis (AD) is common in childhood, with peak prevalence
      in early childhood. However, international comparisons of prevalence have focused
      on older children. We analysed differences in prevalence rates of AD and the
      associations with putative risk and protective factors, among infants in two
      European and two Central American countries. METHODS: In 1-yr old infants
      participating in the International Study of Wheezing in Infants (EISL),
      prevalence of AD and putative risk and protective factors were assessed by a
      questionnaire applied to parents. For each risk/protective factor summary, odds
      ratios with 95% confidence intervals were calculated by means of random effects
      meta-analysis. RESULTS: Data from 9803 infants were analysed. AD prevalence
      varied from 10.6% (Valencia, Spain) to 28.2% (San Pedro Sula, Honduras). Average
      AD prevalences were lower in Europe (14.2%) than in Central America (18.2%, p <
      0.01). Consistent with older children, presence of siblings decreased (OR 0.82
      [0.72-0.94]), whereas family history of asthma (OR 1.32 [1.10-1.59]), rhinitis
      (OR 1.33 [1.14-1.54]) and atopic dermatitis (OR 2.40 [1.89-3.05]) increased the
      risk of infantile AD. However, gender, family size, breastfeeding and socio
      economic status were not associated with AD prevalence. CONCLUSIONS: This study
      shows almost threefold differences in the prevalence of AD in infancy between
      countries. Risk and protective factors involved in the expression of infantile AD
      differ from those in older children, possibly suggesting a different
      pathophysiology. There is a need for additional international epidemiological
      surveys on AD in young children, the peak prevalence age of this condition.

PMID- 25845447
TI  - Iatrogenic Atrial Septal Defect After Cryoballoon Pulmonary Vein Isolation.

PMID- 25845446
TI  - Monitoring the Foetal Phase of Gestation in the Queen With a 12.5-MHz Ultrasound
      Probe and Prediction of the Parturition by Combining the Measurements of Head and
      Abdominal Diameters.
AB  - Ten gestations in six domestic shorthair cats (Europeans) were monitored daily
      during the foetal phase of gestation, from the 28th day after the first mating
      until parturition, using ultrasound with a 12.5-MHz probe. The development of the
      various organs over this period was recorded. The diameters of the head (HD) and
      abdomen (AD) were measured. Skeletal calcification visible on ultrasound occurred
      in a defined order between the 34th and 40th day of gestation. During the last 30
      days of gestation, there was a significant correlation between HD and days before
      parturition (DBP) (r(2)  = 0.99) and between AD and DBP (r(2)  = 0.98). The
      following equations were obtained: DBP = -2.10*HD (mm) + 50.74; DBP = -1.01*AD
      (mm) + 42.19. The confidence intervals were stable over the last 30 days of
      gestation. For the HD, the confidence interval was +/-1 day in 53% of cases and
      +/-2 days in 85% of cases. For the AD, the confidence interval was +/-1 day in
      45% of cases and +/-2 days in 77% of cases. A table obtained by combining the HD
      and AD measurements made it possible to estimate the date of parturition within 2
      days with a reliability of over 85%. 

PMID- 25845448
TI  - Efficacy of Andolast in Mild to Moderate Asthma: A Randomized, Controlled, Double
      Blind Multicenter Study (The Andast Trial).
AB  - BACKGROUND: Andolast is a new airway specific anti-inflammatory agent. The aim of
      the present multicentered, randomized, placebo controlled study is to investigate
      whether andolast produces a therapeutic response greater than placebo in
      asthmatic adult patients. METHODS: 549 symptomatic patients with mild or moderate
      asthma were randomized to receive andolast at three different doses (2, 4, or 8
      mg t.i.d.) or placebo for 12 weeks. Efficacy and safety were evaluated during
      scheduled visits with pulmonary function tests, peak expiratory flow rate (PEFR),
      symptoms diary and quality of life questionnaire. The primary outcome included
      the changes (expressed as percent variation) from baseline of the forced
      expiratory volume in one second (FEV1) absolute values after 12 weeks of
      treatment. FINDINGS: One hundred and thirty one (131) patients were treated with
      andolast at the dose of 2 mg t.i.d., 128 patients at the dose of 4 mg t.i.d., 144
      at the dose of 8 mg t.i.d. and 146 with placebo. Andolast produced a dose
      dependent significant improvement over placebo on airflow obstruction, as shown
      by the changes in FEV1 (andolast 2, 4, 8 mg vs. placebo: p = 0.011), especially
      in a subgroup of patients showing moderate airways obstruction (FEV1<80%pred).
      The mean number of asthma control days and free days significantly increased, the
      average number of inhaled puffs of short-acting alpha2-agonists used as rescue
      medication was significantly reduced as compared with placebo. Andolast also
      significantly decreased the incidence of asthma exacerbation episodes.
      CONCLUSION: Andolast proved to be significantly more effective than placebo in
      improving airflow, and in controlling asthma symptoms both during day and night.

PMID- 25845449
TI  - A rapid and sensitive determination of hypoxic radiosensitizer agent nimorazole
      in rat plasma by LC-MS/MS and its application to a pharmacokinetic study.
AB  - A highly sensitive, accurate and robust LC-MS/MS method was developed and
      validated for determination of nimorazole (NMZ) in rat plasma using metronidazole
      (MNZ) as internal standard (IS). The analyte and IS were extracted from plasma by
      precipitating protein with acetonitrile and were chromatographed using an Agilent
      Poroshell 120, EC-C18 column. The mobile phase was composed of a mixture of
      acetonitrile and 0.1 % formic acid (85:15 v/v). The total run time was 1.5 min
      and injection volume was 5 MUL. Multiple reaction monitoring mode using the
      transitions of m/z 227.1 -> m/z 114.0 for MNZ and m/z 172.10 -> m/z 128.1 for IS
      were monitored on a triple quadrupole mass spectrometer, operating in positive
      ion mode. The calibration curve was linear in the range of 0.25-200 ng/mL (r(2) 
      > 0.9996) and the lower limit of quantification was 0.25 ng/mL in the rat plasma
      samples. Recoveries of NMZ ranged between 88.05 and 95.25%. The precision (intra
      day and inter-day) and accuracy of the quality control samples were 1.25-8.20%
      and -2.50-3.10, respectively. The analyte and IS were found to be stable during
      all sample storage and analysis procedures. The LC-MS/MS method described here
      was validated and successfully applied to pharmacokinetic study in rats.

PMID- 25845450
TI  - Standard excision and reconstruction as an alternative to MMS for giant basal
      cell carcinoma?

PMID- 25845451
TI  - Celebrating the 70(th) birthday of Valery V. Tuchin.

PMID- 25845461
TI  - Large optical nonlinearity induced by singlet fission in pentacene films.
AB  - By creating two triplet excitons from one photo-excited singlet exciton, singlet
      fission in organic semiconductors has drawn tremendous attention for its
      potential applications in boosting the efficiency of solar conversion. Here, we
      show that this carrier-multiplication effect can also be used to dramatically
      improve the nonlinear optical response in organic materials. We have observed
      large optical nonlinearity with a magnitude of chi((3)) up to 10(-9) esu in
      pentacene films, which is further shown to be a result of singlet fission by
      monitoring the temporal dynamics. The potential application of such efficient
      nonlinear optical response has been demonstrated with a singlet-fission-induced
      polarization rotation.

PMID- 25845462
TI  - Modeling and evaluating evidence-based continuing education program in nursing
      home dementia care (MEDCED)--training of care home staff to reduce use of
      restraint in care home residents with dementia. A cluster randomized controlled
      trial.
AB  - OBJECTIVE: The aim of this study was to evaluate the effectiveness of a tailored
      7-month training intervention "Trust Before Restraint," in reducing use of
      restraint, agitation, and antipsychotic medications in care home residents with
      dementia. METHODS: This is a single-blind cluster randomized controlled trial in
      24 care homes within the Western Norway Regional Health Authority 2011-2013.
      RESULTS: From 24 care homes, 274 residents were included in the study, with 118
      in the intervention group and 156 in the control group. Use of restraint was
      significantly reduced in both the intervention group and the control group
      despite unexpected low baseline, with a tendency to a greater reduction in the
      control group. There was a significant reduction in Cohen-Mansfield Agitation
      Inventory score in both the intervention group and the follow-up group with a
      slightly higher reduction in the control group, although this did not reach
      significance and a small nonsignificant increase in use of antipsychotics (14.1
      17.7%) and antidepressants (35.9-38.4%) in both groups. CONCLUSIONS: This study
      reports on the statistically significant reduction in use of restraint in care
      homes, both prior and during the 7-month intervention periods, in both
      intervention and control groups. When interpreted within the context of the
      current climate of educational initiatives to reduce restraint and a greater
      focus on the importance of person-centered care, the study also highlights the
      potential success achieved with national training programs for care staff and
      should be further evaluated to inform future training initiatives both in Norway
      and internationally.

PMID- 25845463
TI  - Determination of zearalenone in maize products by vortex-assisted ionic-liquid
      based dispersive liquid-liquid microextraction with high-performance liquid
      chromatography.
AB  - A novel method has been developed for the analysis of zearalenone in maize
      products by vortex-assisted ionic-liquid-based dispersive liquid-liquid
      microextraction combined with HPLC and fluorescence detection. Maize samples were
      extracted with methanol/water (80:20, v/v) and the extraction solution was then
      used as the dispersive solvent in the microextraction procedure. The analyte was
      rapidly transmitted to a small volume of ionic liquid and was determined by HPLC.
      Various parameters affecting the recovery of the mycotoxin were investigated,
      such as the type and volume of the extraction solvent, the type and volume of the
      dispersive solvent, the pH of the aqueous phase, the salt addition, and the time
      of vortex and centrifugation. Under the optimal experimental conditions, a good
      linearity of the analyte was obtained in the range of 1.0-1000.0 MUg/L with the
      correlation coefficient of 0.9998. The limit of detection (S/N = 3) and
      quantification (S/N = 10) were 0.3 and 1.0 MUg/kg, and the mean recoveries ranged
      from 83.5 to 94.9%, with a relative standard deviation less than 5.0%. The
      proposed method was demonstrated to be simple, cheap, quick, and highly selective
      and was successfully applied to the determination of zearalenone in maize
      products. 

PMID- 25845464
TI  - Telbivudine in liver transplant recipients: Renal protection does not overcome
      the risk of polyneuropathy and myopathy.
AB  - The recently reported benefit of telbivudine for renal function has not been
      systematically studied in long-term liver transplantation (LT) recipients who are
      at high risk for renal impairment. We aimed to examine whether switching
      lamivudine therapy to telbivudine could improve renal function in LT recipients
      who have impaired renal function. This single-center, prospective cohort study
      enrolled LT recipients who were on lamivudine for hepatitis B virus (HBV)
      prophylaxis and who had renal impairment for at least 1 year. Lamivudine was
      switched to telbivudine. The primary outcome was to evaluate the change in renal
      function at weeks 12, 24, 36, and 48. The secondary outcomes were to assess the
      efficacy of telbivudine for HBV prophylaxis and the safety profile of telbivudine
      in the posttransplant setting. After 45 patients were enrolled, the study was
      terminated early because of increased rates of polyneuropathy/myopathy. During
      telbivudine treatment (median, 64 weeks), estimated glomerular filtration rate
      (eGFR) increased in 34 patients (76%). The improvement in renal function was
      prominent after 24 weeks of telbivudine treatment. Telbivudine was effective as
      prophylaxis against HBV recurrence. Twenty-six patients (58%) developed
      polyneuropathy and/or myopathy. The 1-year estimated incidence of
      polyneuropathy/myopathy was 28%. Diabetes was the strongest predictor of
      polyneuropathy/myopathy (hazard ratio, 4.13; 95% confidence interval, 1.49-11.50;
      P = 0.007). In conclusion, although it seems to have a favorable effect in the
      improvement of renal function and seems to be effective in the prevention of HBV
      recurrence, the high risk of polyneuropathy and myopathy hampers the use of
      telbivudine in LT recipients.

PMID- 25845465
TI  - Quantitative single-cell motility analysis of platelet-rich plasma-treated
      endothelial cells in vitro.
AB  - Platelet-rich plasma (PRP) has been widely applied in regenerative therapy due to
      its high concentration of growth factors. Previous in vitro and in vivo studies
      have provided evidence supporting the angiogenic activity of PRP. To more
      directly demonstrate how PRP acts on endothelial cells, we examined the PRP
      induced changes in the motility of human umbilical vein endothelial cells by
      examining the involvement of VEGF. Time-lapse quantitative imaging demonstrated
      that in the initial phase (~2 h) of treatment, PRP substantially stimulated cell
      migration in a wound-healing assay. However, this effect of PRP was not sustained
      at significant levels beyond the initial phase. The average net distance of cell
      migration at 10 h was 0.45 +/- 0.16 mm and 0.82 +/- 0.23 mm in control and PRP
      stimulated cells, respectively. This effect was also demonstrated with
      recombinant human VEGF and was significantly attenuated by a neutralizing anti
      VEGF antibody. Immunofluorescent examination of paxillin and actin fibers
      demonstrated that PRP concomitantly up-regulated focal adhesion and cytoskeletal
      formation. Western blotting analysis of phosphorylated VEGFR2 demonstrated that
      PRP mainly stimulated the phosphorylation of immature VEGFR2 in a dose- and time
      dependent manner, an action that was completely blocked by the neutralizing
      antibody. Taken together, these data suggest that PRP acts directly on
      endothelial cells via the activation of VEGFR2 to transiently up-regulate their
      motility. Thus, the possibility that PRP desensitizes target endothelial cells
      for a relatively long period of time after short-term activation should be
      considered when the controlled release system of PRP components is designed.

PMID- 25845466
TI  - The relationship between fear and pain levels during needle procedures in
      children from the parents' perspective.
AB  - BACKGROUND: The primary objective was to determine the levels of and potential
      relationships between procedure-related fear and pain in children. Secondary
      objectives were to determine if there are associations between the child's age
      and sex, diagnostic group, time since diagnosis, time since last needle
      insertion, cortisol levels and the parent's fear level in relation to fear and
      pain. METHODS: The child's level of pain and fear was reported by parents on 0
      100 mm visual analogue scales (VAS). One hundred and fifty-one children were
      included consecutively when undergoing routine needle insertion into a
      subcutaneously implanted intravenous port. All children were subjected to one
      needle insertion following topical anaesthesia (EMLA) application. The effect of
      the child's age and sex, diagnostic group, time since diagnosis, time since last
      needle insertion, cortisol change levels and the parent's fear level, on fear and
      pain levels was investigated with multiple regression analysis. RESULTS: The
      needle-related fear level (VAS mean 28 mm) was higher than the needle-related
      pain level (VAS mean 17 mm) when topical anaesthesia is used according to
      parents' reports (n = 151, p < 0.001). With fear as the dependent variable, age
      and pain were significantly associated and explained 33% of the variance, and
      with pain as the dependent variable, fear, parents' fear and change in cortisol
      level were significantly associated and explained 38% of the variance.
      CONCLUSIONS: According to parents, children experienced more fear than pain
      during needle insertion when topical anaesthesia is used. Therefore, in addition
      to pain management, an extended focus on fear-reducing interventions is suggested
      for needle procedures.

PMID- 25845467
TI  - Prospective quality-of-life outcomes for low-risk prostate cancer: Active
      surveillance versus radical prostatectomy.
AB  - BACKGROUND: For patients with low-risk prostate cancer (PCa), active surveillance
      (AS) may produce oncologic outcomes comparable to those achieved with radical
      prostatectomy (RP). Health-related quality-of-life (HRQoL) outcomes are important
      to consider, yet few studies have examined HRQoL among patients with PCa who were
      managed with AS. In this study, the authors compared longitudinal HRQoL in a
      prospective, racially diverse, and contemporary cohort of patients who underwent
      RP or AS for low-risk PCa. METHODS: Beginning in 2007, HRQoL data from validated
      questionnaires (the Expanded Prostate Cancer Index Composite and the 36-item RAND
      Medical Outcomes Study short-form survey) were collected by the Center for
      Prostate Disease Research in a multicenter national database. Patients aged <=75
      years who were diagnosed with low-risk PCa and elected RP or AS for initial
      disease management were followed for 3 years. Mean scores were estimated using
      generalized estimating equations adjusting for baseline HRQoL, demographic
      characteristics, and clinical patient characteristics. RESULTS: Of the patients
      with low-risk PCa, 228 underwent RP, and 77 underwent AS. Multivariable analysis
      revealed that patients in the RP group had significantly worse sexual function,
      sexual bother, and urinary function at all time points compared with patients in
      the AS group. Differences in mental health between groups were below the
      threshold for clinical significance at 1 year. CONCLUSIONS: In this study, no
      differences in mental health outcomes were observed, but urinary and sexual HRQoL
      were worse for patients who underwent RP compared with those who underwent AS for
      up to 3 years. These data offer support for the management of low-risk PCa with
      AS as a means for postponing the morbidity associated with RP without concomitant
      declines in mental health.

PMID- 25845468
TI  - Multisite evaluations of a T2 -relaxation-under-spin-tagging (TRUST) MRI
      technique to measure brain oxygenation.
AB  - PURPOSE: Venous oxygenation (Yv ) is an important index of brain physiology and
      may be indicative of brain diseases. A T2 -relaxation-under-spin-tagging (TRUST)
      MRI technique was recently developed to measure Yv . A multisite evaluation of
      this technique would be an important step toward broader availability and
      potential clinical utilizations of Yv measures. METHODS: TRUST MRI was performed
      on a total of 250 healthy subjects, 125 from the developer's site and 25 each
      from five other sites. All sites were equipped with a 3 Tesla (T) MRI of the same
      vendor. The estimated Yv and the standard error (SE) of the estimation epsilonYv
      were compared across sites. RESULTS: The averaged Yv and epsilonYv across six
      sites were 61.1% +/- 1.4% and 1.3% +/- 0.2%, respectively. Multivariate
      regression analysis showed that the estimated Yv was dependent on age (P = 0.009)
      but not on performance site. In contrast, the SE of the Yv estimation was site
      dependent (P = 0.024) but was less than 1.5%. Further analysis revealed that
      epsilonYv was positively associated with the amount of subject motion (P < 0.001)
      but negatively associated with blood signal intensity (P < 0.001). CONCLUSION:
      This work suggests that TRUST MRI can yield equivalent results of Yv estimation
      across different sites.

PMID- 25845469
TI  - MED23-associated intellectual disability in a non-consanguineous family.
AB  - Intellectual disability (ID) is a heterogeneous condition arising from a variety
      of environmental and genetic factors. Among these causes are defects in
      transcriptional regulators. Herein, we report on two brothers in a
      nonconsanguineous family with novel compound heterozygous, disease-segregating
      mutations (NM_015979.3: [3656A > G];[4006C > T], NP_057063.2: [H1219R];[R1336X])
      in MED23. This gene encodes a subunit of the Mediator complex that modulates the
      expression of RNA polymerase II-dependent genes. These brothers, who had profound
      ID, spasticity, congenital heart disease, brain abnormalities, and atypical
      electroencephalography, represent the first case of MED23-associated ID in a non
      consanguineous family. They also expand upon the clinical features previously
      reported for mutations in this gene.

PMID- 25845470
TI  - Opioid analgesic prescribing in Australia: a focus on gender and age.
AB  - PURPOSE: The use of prescription opioid analgesics has been increasing over the
      last few decades in Australia. In particular, oxycodone and fentanyl have
      increased substantially. We examined the gender and age trends in the prescribing
      of subsidised opioid analgesics in the Australian population for non-palliative
      care indications. METHODS: We analysed the Medicare Australia and Drug
      Utilisation Sub-Committee databases for prescription data from 2002 to 2009 in 10
      year age groups and by gender. Prescriptions were converted to Defined Daily
      Doses (DDD)/1000/day using Australian Bureau of Statistics population data.
      RESULTS: Overall use increased progressively in 2002-2009 from 12.95 to 16.08
      DDD/1000 population/day (average annual increase 3.4%). Codeine was the most
      widely used agent followed by tramadol then oxycodone. Dispensed use increased in
      those aged in their 20s and 30s to plateau between 30 and 59 years for the three
      most preferred analgesics. The peak use of higher dose formulations of oxycodone
      was seen in males from 40 years. The highest dose formulation of tramadol was
      preferred in those aged up to approximately 70 years. CONCLUSIONS: Reasons for
      increased use may include increased prevalence of people with cancer and use for
      acute pain. The overall benefit and risk in this escalation of opioid use are
      difficult to determine; however, the increasing risk of tolerance, dependence,
      overdose and drug diversion suggests to clinicians and policy makers that this
      escalation may not be in the best interest of all Australians.

PMID- 25845471
TI  - Effect of mineral nutrients on the uptake of Cr(VI) by maize plants.
AB  - To determine the potential of maize plants for phytoextraction of chromium (Cr),
      and the effect that some mineral nutrients have on this process, the uptake of
      this metal was analyzed in vitro. 12-day-old plants were incubated in nutrient
      solutions with 200 or 250 MUM potassium chromate and 3mM supplements of nitrate,
      phosphate or sulfate. The greatest accumulation of Cr after 48 hours was in
      plants that were supplemented with nitrate (800 and 350 mg kg(-1) DW for roots
      and stems, respectively) with bioaccumulation factors of 18 and 7 in the roots
      and in the foliage, respectively. Moreover, the translocation factor from root to
      leaves was 0.4 when nitrate was supplemented; thus, the addition of this nutrient
      is recommended when the crop is to be used for phytoextraction of Cr. Considering
      the results obtained, the high biomass produced by this crop and the extensive
      knowledge of agricultural practices for this plant, we believe that maize has the
      potential to be considered in the phytoextraction of Cr, based on preliminary
      assays of soil conditions.

PMID- 25845477
TI  - No cardiomyopathy in X-linked myopathy with excessive autophagy.
AB  - In X-linked myopathy with excessive autophagy (XMEA) progressive sarcoplasmic
      accumulation of autolysosomes filled with undegraded debris leads to atrophy and
      weakness of skeletal muscles. XMEA is caused by compromised acidification of
      lysosomes resulting from hypofunction of the proton pump vacuolar ATPase (V
      ATPase), due to hypomorphic mutations in VMA21, whose protein product assembles V
      ATPase. To what extent the cardiac muscle is affected is unknown. Therefore we
      performed a comprehensive cardiac evaluation in four male XMEA patients, and also
      examined pathology of one deceased patient's cardiac and skeletal muscle. None of
      the symptomatic men (aged 25-48 years) had history or symptoms of cardiomyopathy.
      Resting electrocardiograms and echocardiographies were normal. MRI showed normal
      left ventricle ejection fraction and myocardial mass. Myocardial late-gadolinium
      enhancement was not detected. The deceased patient's skeletal but not cardiac
      muscle showed characteristic accumulation of autophagic vacuoles. In conclusion,
      in classic XMEA the myocardium is structurally, electrically and clinically
      spared. 

PMID- 25845478
TI  - Novel PSTPIP1 gene mutation in a patient with pyogenic arthritis, pyoderma
      gangrenosum and acne (PAPA) syndrome.
AB  - INTRODUCTION: Pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome
      is a rare autosomal dominant disease that usually presents in childhood with
      recurrent sterile arthritis. As the child ages into puberty, cutaneous features
      develop and arthritis subsides. We report the case of a now 25-year-old male
      patient with PAPA syndrome with the E250K mutation in PSTPIP1. We also present a
      systematic literature review of other PAPA cases. METHOD: We conducted a
      literature search of PubMed using the following search terms: E250K mutation,
      PSTPIP1, and PAPA. RESULTS: PAPA syndrome is caused by mutations on chromosome
      15q affecting the proline-serine-threonine phosphatase-interacting protein 1
      (PSTPIP1) gene, also known as CD2-binding protein 1 (CD2BP1). The reported cases
      of PAPA syndrome currently in the literature involve mutations in A230T and
      E250Q. One case of a novel E250K mutation has been reported, which presented with
      a different phenotype to previously described cases of PAPA syndrome. CONCLUSION:
      With variation present between disease presentations from case to case, it is
      possible that the spectrum of PAPA syndrome is wider than currently thought.
      Further research is needed which may uncover an as-yet undiscovered genetic
      abnormality linking these interrelated diseases together.

PMID- 25845479
TI  - Impact of sampling time deviations on the prediction of the area under the curve
      using regression limited sampling strategies.
AB  - The regression limited sampling strategy approach (R-LSS), which is based on a
      small number of blood samples drawn at selected time points, has been used as an
      alternative method for the estimation of the area under the concentration-time
      curve (AUC). However, deviations from planned sampling times may affect the
      performance of R-LSS, influencing related therapeutic decisions and outcomes. The
      aim of this study was to investigate the impact of different sampling time
      deviation (STD) scenarios on the estimation of AUC by the R-LSS using a
      simulation approach. Three types of scenarios were considered going from the
      simplest case of fixed deviations, to random deviations and then to a more
      realistic case where deviations of mixed nature can occur. In addition, the
      sensitivity of the R-LSS to STD in each involved sampling point was evaluated. A
      significant impact of STD on the performance of R-LSS was demonstrated. The
      tolerance of R-LSS to STD was found to depend not only on the number of sampling
      points but more importantly on the duration of the sampling process. Sensitivity
      analysis showed that sampling points at which rapid concentration changes occur
      were relatively more critical for AUC prediction by R-LSS. As a practical
      approach, nomograms were proposed, where the expected predictive performance of R
      LSS was provided as a function of STD information. The investigation of STD
      impact on the predictive performance of R-LSS is a critical element and should be
      routinely performed to guide R-LSS selection and use.

PMID- 25845480
TI  - Effect of planar microelectrode geometry on neuron stimulation: finite element
      modeling and experimental validation of the efficient electrode shape.
AB  - BACKGROUND: Microelectrode arrays have been used successfully for neuronal
      stimulation both in vivo and in vitro. However, in most instances currents
      required to activate the neurons have been in un-physiological ranges resulting
      in neuronal damage and cell death. There is a need to develop electrodes which
      require less stimulation current for neuronal activation with physiologically
      relevant efficacy and frequencies. NEW METHOD: The objective of the present study
      was to examine and compare the stimulation efficiency of different electrode
      geometries at the resolution of a single neuron. We hypothesized that increasing
      the electrode perimeter will increase the maximum current density at the edges
      and enhance stimulation efficiency. To test this postulate, the neuronal
      stimulation efficacy of common circular electrodes (smallest perimeter) was
      compared with star (medium perimeter), and spiral (largest perimeter with
      internal boundaries) electrodes. We explored and compared using both a finite
      element model and in vitro stimulation of neurons isolated from Lymnaea central
      ganglia. RESULTS: Interestingly, both the computational model and the live
      neuronal stimulation experiments demonstrated that the common circular
      microelectrode requires less stimulus to activate a cell compared to the other
      two electrode shapes with the same surface area. Our data further revealed that
      circular electrodes exhibit the largest sealing resistance, stimulus transfer,
      and average current density among the three types of electrodes tested.
      COMPARISON WITH EXISTING METHODS: Average current density and not the maximum
      current density at the edges plays an important role in determining the electrode
      stimulation efficiency. CONCLUSION: Circular shaped electrodes are more efficient
      in inducing a change in neuronal membrane potential.

PMID- 25845481
TI  - Motor imagery classification via combinatory decomposition of ERP and ERSP using
      sparse nonnegative matrix factorization.
AB  - BACKGROUND: Brain activities could be measured by devices like EEG, MEG, MRI etc.
      in terms of electric or magnetic signal, which could provide information from
      three domains, i.e., time, frequency and space. Combinatory analysis of these
      features could definitely help to improve the classification performance on brain
      activities. NMF (nonnegative matrix factorization) has been widely applied in
      pattern extraction tasks (e.g., face recognition, gene data analysis) which could
      provide physically meaningful explanation of the data. However, brain signals
      also take negative values, so only spectral feature has been employed in existing
      NMF studies for brain computer interface. In addition, sparsity is an intrinsic
      characteristic of electric signals. NEW METHOD: To incorporate sparsity
      constraint and enable analysis of time domain feature using NMF, a new solution
      for motor imagery classification is developed, which combinatorially analyzes the
      ERP (event related potential, time domain) and ERSP (event related spectral
      perturbation, frequency domain) features via a modified mixed alternating least
      square based NMF method (MALS-NMF for short). RESULTS: Extensive experiments have
      verified the effectivity the proposed method. The results also showed that
      imposing sparsity constraint on the coefficient matrix in ERP factorization and
      basis matrix in ERSP factorization could better improve the algorithm
      performance. COMPARISON WITH EXISTING METHODS: Comparisons with other eight
      representative methods have further verified the superiority of the proposed
      method. CONCLUSIONS: The MALS-NMF method is an effective solution for motor
      imagery classification and has shed some new light into the field of brain
      dynamics pattern analysis.

PMID- 25845482
TI  - Non-invasive mapping of bilateral motor speech areas using navigated transcranial
      magnetic stimulation and functional magnetic resonance imaging.
AB  - BACKGROUND: Navigated transcranial magnetic stimulation (nTMS) is a modern
      precise method to activate and study cortical functions noninvasively. We
      hypothesized that a combination of nTMS and functional magnetic resonance imaging
      (fMRI) could clarify the localization of functional areas involved with motor
      control and production of speech. NEW METHOD: Navigated repetitive TMS (rTMS)
      with short bursts was used to map speech areas on both hemispheres by inducing
      speech disruption during number recitation tasks in healthy volunteers. Two
      experienced video reviewers, blinded to the stimulated area, graded each trial
      offline according to possible speech disruption. The locations of speech
      disrupting nTMS trials were overlaid with fMRI activations of word generation
      task. RESULTS:  COMPARISON WITH EXISTING METHODS: Speech disruptions were
      produced on both hemispheres by nTMS, though there were more disruptive
      stimulation sites on the left hemisphere. Grade of the disruptions varied from
      subjective sensation to mild objectively recognizable disruption up to total
      speech arrest. The distribution of locations in which speech disruptions could be
      elicited varied among individuals. On the left hemisphere the locations of
      disturbing rTMS bursts with reviewers' verification followed the areas of fMRI
      activation. Similar pattern was not observed on the right hemisphere.
      CONCLUSIONS: The reviewer-verified speech disruptions induced by nTMS provided
      clinically relevant information, and fMRI might explain further the function of
      the cortical area. nTMS and fMRI complement each other, and their combination
      should be advocated when assessing individual localization of speech network.

PMID- 25845483
TI  - Bioaerosol emissions from open microalgal processes and their potential
      environmental impacts: what can be learned from natural and anthropogenic aquatic
      environments?
AB  - Open processes for microalgae mass cultivation and/or wastewater treatment
      present an air-water interface. Similarly to other open air-aquatic environments,
      they are subject to contamination, but as such, they also represent a source of
      bioaerosols. Indeed, meteorological, physico-chemical and biological factors
      cause aerial dispersion of the planktonic community. Operating conditions like
      liquid mixing or gas injection tend to both enhance microbial activity, as well
      as intensify aerosolization. Bacteria, virus particles, fungi and protozoa, in
      addition to microalgae, are all transient or permanent members of the planktonic
      community and can thus be emitted as aerosols. If they should remain viable,
      subsequent deposition on various habitats could instigate their colonization of
      other environments and the potential expression of their ecological function. 

PMID- 25845484
TI  - Transcriptional dynamics of Phytophthora infestans during sequential stages of
      hemibiotrophic infection of tomato.
AB  - Hemibiotrophic plant pathogens, such as the oomycete Phytophthora infestans,
      employ a biphasic infection strategy, initially behaving as biotrophs, where
      minimal symptoms are exhibited by the plant, and subsequently as necrotrophs,
      feeding on dead plant tissue. The regulation of this transition and the breadth
      of molecular mechanisms that modulate plant defences are not well understood,
      although effector proteins secreted by the pathogen are thought to play a key
      role. We examined the transcriptional dynamics of P. infestans in a compatible
      interaction with its host tomato (Solanum lycopersicum) at three infection
      stages: biotrophy; the transition from biotrophy to necrotrophy; and necrotrophy.
      The expression data suggest a tight temporal regulation of many pathways
      associated with the suppression of plant defence mechanisms and pathogenicity,
      including the induction of putative cytoplasmic and apoplastic effectors. Twelve
      of these were experimentally evaluated to determine their ability to suppress
      necrosis caused by the P. infestans necrosis-inducing protein PiNPP1.1 in
      Nicotiana benthamiana. Four effectors suppressed necrosis, suggesting that they
      might prolong the biotrophic phase. This study suggests that a complex regulation
      of effector expression modulates the outcome of the interaction. 

PMID- 25845485
TI  - Ethical issues raised by a ban on the sale of electronic nicotine devices.
AB  - BACKGROUND: Some countries have banned the sale of electronic nicotine delivery
      systems (ENDS). AIMS: We analyse the ethical issues raised by this ban and
      various ways in which the sale of ENDS could be permitted. METHOD: We examine the
      ban and alternative policies in terms of the degree to which they respect ethical
      principles of autonomy, beneficence, non-maleficence and justice, as follows.
      RESULTS: Respect for autonomy: prohibiting ENDS infringes on smokers' autonomy to
      use a less harmful nicotine product while inconsistently allowing individuals to
      begin and continue smoking cigarettes. Non-maleficence: prohibition is supposed
      to prevent ENDS recruiting new smokers and discouraging smokers from quitting,
      but it has not prevented uptake of ENDS. It also perpetuates harm by preventing
      addicted smokers from using a less harmful nicotine product. Beneficence: ENDS
      could benefit addicted smokers by reducing their health risks if they use them to
      quit and do not engage in dual use. Distributive justice: lack of access to ENDS
      disadvantages smokers who want to reduce their health risks. Different national
      policies create inequalities in the availability of products to smokers
      internationally. CONCLUSIONS: We do not have to choose between a ban and an
      unregulated free market. We can ethically allow ENDS to be sold in ways that
      allow smokers to reduce the harms of smoking while minimizing the risks of
      deterring quitting and increasing smoking among youth.

PMID- 25845486
TI  - Babies born before arrival to hospital and maternity unit closures in Queensland
      and Australia.
AB  - BACKGROUND: Evidence suggests the closure of maternity units is associated with
      an increase in babies born before arrival (BBA). AIM: To explore the association
      between the number of maternity units in Australia and Queensland by birthing
      numbers, BBA rate and geographic remoteness of the health district where the
      mother lives. METHODS: A retrospective study utilised routinely collected
      perinatal data (1992-2011). Pearson correlation tested the relationship between
      BBA rate and number of maternity units. Linear regression examined this
      association over time. FINDINGS: During 1992-2011, the absolute numbers
      (N=22,814) of women having a BBA each year in Australia increased by 47% (N=836
      1233); and 206% (n=140-429) in Queensland. This coincided with a 41% reduction in
      maternity units in Australia (N=623-368=18 per year) and a 28% reduction in
      Queensland (n=129-93). BBA rates increased significantly across Australia,
      r=0.837, n=20 years, p<0.001 and Queensland, r=0.917, n=20 years, p<0.001 and
      this was negatively correlated with the number of maternity units in Australia,
      r=-0.804, n=19 years, p<0.001 and Queensland, r=-0.906, n=19 years, p<0.001.
      CONCLUSIONS: The closure of maternity units over a 20-year period across
      Australia and Queensland is significantly associated with increased BBA rates.
      The distribution is not limited to rural and remote areas. Given the high risk of
      adverse maternal and neonatal outcomes associated with BBA, it is time to revisit
      the closure of units.

PMID- 25845487
TI  - Topical treatment with pterostilbene, a natural phytoalexin, effectively protects
      hairless mice against UVB radiation-induced skin damage and carcinogenesis.
AB  - The aim of our study was to investigate in the SKH-1 hairless mouse model the
      effect of pterostilbene (Pter), a natural dimethoxy analog of resveratrol (Resv),
      against procarcinogenic ultraviolet B radiation (UVB)-induced skin damage. Pter
      prevented acute UVB (360 mJ/cm(2))-induced increase in skin fold, thickness, and
      redness, as well as photoaging-associated skin wrinkling and hyperplasia. Pter,
      but not Resv, effectively prevented chronic UVB (180 mJ/cm(2), three doses/week
      for 6 months)-induced skin carcinogenesis (90% of Pter-treated mice did not
      develop skin carcinomas, whereas a large number of tumors were observed in all
      controls). This anticarcinogenic effect was associated with (a) maintenance of
      skin antioxidant defenses (i.e., glutathione (GSH) levels, catalase, superoxide,
      and GSH peroxidase activities) close to control values (untreated mice) and (b)
      an inhibition of UVB-induced oxidative damage (using as biomarkers 8-hydroxy-2'
      deoxyguanosine, protein carbonyls, and isoprostanes). The molecular mechanism
      underlying the photoprotective effect elicited by Pter was further evaluated
      using HaCaT immortalized human keratinocytes and was shown to involve potential
      modulation of the Nrf2-dependent antioxidant response.

PMID- 25845488
TI  - Analysis of quality improvement efforts in preventing glucocorticoid-induced
      osteoporosis.
AB  - OBJECTIVE: To report and analyze quality improvement (QI) efforts that are aimed
      at increasing adherence to preventive guidelines for glucocorticoid-induced
      osteoporosis (GIOP). METHODS: We performed a PubMed literature search for full
      length articles in English between 1966 and 2013, describing approaches for
      improving the quality of GIOP care. We reviewed articles using a structured
      approach and abstracted information on the patient population, study design, QI
      intervention, and primary outcome measures. A descriptive analysis was then
      performed. RESULTS: Literature search identified 661 articles; 38 were screened
      by abstract, 10 were identified for full review, and 7 were included. Two non
      randomized, uncontrolled studies of system changes showed significant
      improvements in GIOP prevention: one increased concomitant prescriptions of
      glucocorticoids and calcium (37-49%, p < 0.0001) and vitamin D (38-53%, p <
      0.0001) using a computerized order entry system; another used a dedicated
      clinical team to increase vitamin D levels from 19.5 to 29.4 (p = 0.001) and
      improve GIOP-related habits. Five articles described education-based
      interventions, including 3 randomized controlled trials (RCTs). Two non
      significant RCTs focused on physicians, but one directed towards pharmacists and
      patients did increase calcium supplementation in the intervention vs. control arm
      (55.7% vs. 31.6%, p < 0.05). Two other non-randomized educational interventions
      did not show benefits. Comparison of articles was limited by the heterogeneity of
      the intervention methods and outcome measures used. CONCLUSION: None of the
      interventions produced robust changes, with overall adherence to GIOP guidelines
      remaining low. System-based interventions appeared more effective than education
      based interventions, but a diverse array of factors likely needs to be addressed,
      requiring more randomized controlled trials and greater standardization of
      outcome measures.

PMID- 25845489
TI  - Antithrombotic therapy for left ventricular assist devices in adults: a
      systematic review.
AB  - BACKGROUND: Left ventricular assist devices (LVADs) have dramatically increased
      the survival of adults with end-stage systolic heart failure. However, rates of
      bleeding and thromboembolism remain high. OBJECTIVES: We completed a systematic
      review to evaluate outcomes of adults with LVADs treated with various
      anticoagulant and antiplatelet strategies. METHODS: Databases were searched using
      the terms 'assist device', 'thrombosis', and 'anticoagulant' or 'platelet
      aggregation inhibitor' with appropriate synonyms, device names and manufacturers.
      RESULTS AND CONCLUSIONS: Of 977 manuscripts, 24 articles met the inclusion
      criteria of adults with implanted LVADs where clinical outcomes were defined
      based on anticoagulant and/or antiplatelet regimen. Most studies reported
      treatment with unfractionated heparin post-operatively which was transitioned to
      a vitamin K antagonist (VKA). Goal INR varied between 1.5-3.5. Antiplatelet
      regimens ranged from no treatment to dual therapy. Definition of major bleeding
      differed between trials and incidence varied between 0% and 58%. The available
      evidence could not demonstrate a clear benefit of aspirin compared with VKA
      therapy alone [stroke RR 1.02 (95% CI 0.49-2.1)]. There was a suggestion that
      treatment with aspirin and dipyridamole decreased the risk of thromboembolism
      compared to aspirin [RR 0.50 (0.36-0.68)], but the comparison is limited by
      differences in demographics, devices, and INR goals among studies. Additionally,
      most studies did not blind investigators to outcomes thus contributing to an
      increased risk for bias. Clinical equipoise exists as to the most appropriate
      antithrombotic therapy in LVAD patients. Randomization between regimens within a
      prospective trial is needed to define the treatment regimen that minimizes both
      bleeding and thrombotic complications.

PMID- 25845491
TI  - Immunoglobulin A in serum: an old acquaintance as a new prognostic biomarker in
      idiopathic pulmonary fibrosis.
AB  - Immunoglobulin (Ig)A is an important immunoglobulin in mucosal immunity and
      protects the lungs against invading pathogens. The production of IgA is regulated
      by transforming growth factor (TGF)-beta, a versatile cytokine and key player in
      the pathogenesis of pulmonary fibrosis. TGF-beta is up-regulated in patients with
      idiopathic pulmonary fibrosis (IPF), but difficult to use as a biomarker. The aim
      of this study was to evaluate the prognostic value of IgA in serum in patients
      with IPF. We examined IgA levels at time of diagnosis in 86 patients diagnosed
      with IPF. Mean serum IgA level in IPF is 3.22 g/l and regression analyses showed
      a significant association with mortality (hazard ratio = 1.445, P = 0.002). A
      significantly worse survival was found in patients with IgA serum levels > 2.85
      g/l compared to patients with lower IgA serum levels (P = 0.003). These findings
      were confirmed in a duplication cohort. In conclusion, the level of IgA in blood
      is a promising prognostic marker in IPF and can be implemented easily in the
      hospital setting. Future studies are warranted to investigate if repeated
      measurements of serum IgA can further improve the performance of serum IgA as a
      prognostic marker. 

PMID- 25845492
TI  - Parental reporting of response to oral cannabis extracts for treatment of
      refractory epilepsy.
AB  - OBJECTIVE: Oral cannabis extracts (OCEs) have been used in the treatment of
      epilepsy; however, no studies demonstrate clear efficacy. We report on a cohort
      of pediatric patients with epilepsy who were given OCE and followed in a single
      tertiary epilepsy center. METHODS: A retrospective chart review of children and
      adolescents who were given OCE for treatment of their epilepsy was performed.
      RESULTS: Seventy-five patients were identified of which 57% reported any
      improvement in seizure control and 33% reported a >50% reduction in seizures
      (responders). If the family had moved to CO for OCE treatment, the responder rate
      was 47% vs. 22% for children who already were in CO. The responder rate varied
      based on epilepsy syndrome: Dravet 23%, Doose 0%, and Lennox-Gastaut syndrome
      (LGS) 88.9%. The background EEG of the 8 responders where EEG data were available
      was not improved. Additional benefits reported included: improved
      behavior/alertness (33%), improved language (10%), and improved motor skills
      (10%). Adverse events (AEs) occurred in 44% of patients including increased
      seizures (13%) and somnolence/fatigue (12%). Rare adverse events included
      developmental regression, abnormal movements, status epilepticus requiring
      intubation, and death. SIGNIFICANCE: Our retrospective study of OCE use in
      pediatric patients with epilepsy demonstrates that some families reported patient
      improvement with treatment; however, we also found a variety of challenges and
      possible confounding factors in studying OCE retrospectively in an open-labeled
      fashion. We strongly support the need for controlled, blinded studies to evaluate
      the efficacy and safety of OCE for treatment of pediatric epilepsies using
      accurate seizure counts, formal neurocognitive assessments, as well as EEG as a
      biomarker. This study provides Class III evidence that OCE is well tolerated by
      children and adolescents with epilepsy.

PMID- 25845493
TI  - Cross-species pharmacological characterization of the allylglycine seizure model
      in mice and larval zebrafish.
AB  - Treatment-resistant seizures affect about a third of patients suffering from
      epilepsy. To fulfill the need for new medications targeting treatment-resistant
      seizures, a number of rodent models offer the opportunity to assess a variety of
      potential treatment approaches. The use of such models, however, has proven to be
      time-consuming and labor-intensive. In this study, we performed pharmacological
      characterization of the allylglycine (AG) seizure model, a simple in vivo model
      for which we demonstrated a high level of treatment resistance. (d,l)
      Allylglycine inhibits glutamic acid decarboxylase (GAD) - the key enzyme in gamma
      aminobutyric acid (GABA) biosynthesis - leading to GABA depletion, seizures, and
      neuronal damage. We performed a side-by-side comparison of mouse and zebrafish
      acute AG treatments including biochemical, electrographic, and behavioral
      assessments. Interestingly, seizure progression rate and GABA depletion kinetics
      were comparable in both species. Five mechanistically diverse antiepileptic drugs
      (AEDs) were used. Three out of the five AEDs (levetiracetam, phenytoin, and
      topiramate) showed only a limited protective effect (mainly mortality delay) at
      doses close to the TD50 (dose inducing motor impairment in 50% of animals) in
      mice. The two remaining AEDs (diazepam and sodium valproate) displayed protective
      activity against AG-induced seizures. Experiments performed in zebrafish larvae
      revealed behavioral AED activity profiles highly analogous to those obtained in
      mice. Having demonstrated cross-species similarities and limited efficacy of
      tested AEDs, we propose the use of AG in zebrafish as a convenient and high
      throughput model of treatment-resistant seizures. 

PMID- 25845494
TI  - Self-reported aggressiveness during treatment with levetiracetam correlates with
      depression.
AB  - PURPOSE: The purpose of this study was to identify clinical correlates of self
      reported aggressiveness (SRA) in patients with epilepsy treated with
      levetiracetam (LEV) with special reference to the role of depression. METHODS: A
      consecutive sample of adult outpatients with epilepsy was assessed with the
      Neurological Disorder Depression Inventory for Epilepsy, the Adverse Event
      Profile (AEP), and the Emotional Thermometer. RESULTS: From a total sample of 163
      consecutive patients treated with LEV, SRA at any level (from rarely a problem to
      always) was associated with a 7-fold increased risk of being depressed (95% CI:
      3.0-17.5; p<0.001). Self-reported aggressiveness was reported as "always" a
      problem by 9.8% of the patients. In these patients, apart from depression, SRA
      was associated with high AEP total scores (55.1 vs. 39.3; p<0.001) and
      polytherapy (43.8% vs. 19.8%; p=0.034). Anxiety scores were not elevated (4.9 vs.
      3.6; p=0.183). CONCLUSIONS: Self-reported aggressiveness during treatment with
      LEV is not an isolated symptom but is associated with depressed mood. Anxiety
      mediated mechanisms do not seem to be involved.

PMID- 25845496
TI  - 3,4-Dihydroxyphenylacetic acid, a microbiota-derived metabolite of quercetin,
      protects against pancreatic beta-cells dysfunction induced by high cholesterol.
AB  - Cholesterol plays an important role in inducing pancreatic beta-cell dysfunction,
      characterized by an impaired insulin secretory response to glucose, representing
      a hallmark of the transition from pre-diabetes to diabetes. 3,4
      dihydroxyphenylacetic acid (ES) is a scarcely studied microbiota-derived
      metabolite of quercetin with antioxidant properties. The aim of this study was to
      determine the protective effect of ES against apoptosis, mitochondrial
      dysfunction and oxidative stress induced by cholesterol in Min6 pancreatic beta
      cells. Cholesterol decreased viability, induced apoptosis and mitochondrial
      dysfunction by reducing complex I activity, mitochondrial membrane potential, ATP
      levels and oxygen consumption. Cholesterol promoted oxidative stress by
      increasing cellular and mitochondrial reactive oxygen species and lipid
      peroxidation and decreasing antioxidant enzyme activities; in addition, it
      slightly increased Nrf2 translocation to the nucleus. These events resulted in
      the impairment of the glucose-induced insulin secretion. ES increased Nrf2
      translocation to the nucleus and protected pancreatic beta-cells against impaired
      insulin secretion induced by cholesterol by preventing oxidative stress,
      apoptosis and mitochondrial dysfunction. Nrf2 activation seems to be involved in
      the mechanisms underlying the antioxidant protection exerted by ES in addition to
      preventing the disruption of antioxidant enzymatic defenses. Although additional
      in vivo experiments are required, this metabolite is suggested as a promising
      drug target for the prevention of the pathological development from a pre
      diabetic to a diabetic state. 

PMID- 25845495
TI  - Risk stratification with cervical length and fetal fibronectin in women with
      threatened preterm labor before 34 weeks and not delivering within 7 days.
AB  - OBJECTIVE: To stratify the risk of spontaneous preterm delivery using cervical
      length (CL) and fetal fibronectin (fFN) in women with threatened preterm labor
      who remained pregnant after 7 days. DESIGN: Prospective observational study.
      SETTING: Nationwide cohort of women with threatened preterm labor from the
      Netherlands. POPULATION: Women with threatened preterm labor between 24 and 34
      weeks with a valid CL and fFN measurement and remaining pregnant 7 days after
      admission. METHODS: Kaplan-Meier and Cox proportional hazards models were used to
      estimate cumulative percentages and hazard ratios (HR) for spontaneous delivery.
      MAIN OUTCOME MEASURES: Spontaneous delivery between 7 and 14 days after initial
      presentation and spontaneous preterm delivery before 34 weeks. RESULTS: The risk
      of delivery between 7 and 14 days was significantly increased for women with a CL
      < 15 mm or a CL >=15 to <30 mm and a positive fFN, compared with women with a CL
      >=30 mm: HR 22.3 [95% confidence interval (CI) 2.6-191] and 14 (95% CI 1.8-118),
      respectively. For spontaneous preterm delivery before 34 weeks the risk was
      increased for women with a CL < 15 mm [HR 6.3 (95% CI 2.6-15)] or with a CL >=15
      to <30 mm with either positive fFN [HR 3.6 (95% CI 1.5-8.7)] or negative fFN [HR
      3.0 (95% CI 1.2-7.1)] compared with women with a CL >= 30 mm. CONCLUSIONS: In
      women remaining pregnant 7 days after threatened preterm labor, CL and fFN
      results can be used in risk stratification for spontaneous delivery.

PMID- 25845497
TI  - Receptor channel TRPC6 orchestrate the activation of human hepatic stellate cell
      under hypoxia condition.
AB  - Hepatic stellate cells (HSCs), a specialized stromal cytotype have a great impact
      on the biological behaviors of liver diseases. Despite this fact, the underlying
      mechanism that regulates HSC still remains poorly understood. The aim of the
      present study was to understand the role of TRPC6 signaling in regulating the
      molecular mechanism of HSCs in response to hypoxia. In the present study we
      showed that under hypoxia condition, the upregulated Hypoxia Inducible Factor
      1alpha (HIF1alpha) increases NICD activation, which in turn induces the
      expression of transient receptor potential channel 6 (TRPC6) in HSC line lx-2.
      TRPC6 causes a sustained elevation of intracellular calcium which is coupled with
      the activation of the calcineurin-nuclear factor of activated T-cell (NFAT)
      pathway which activates the synthesis of extracellular matrix proteins. TRPC6
      also activates SMAD2/3 dependent TGF-beta signaling in facilitating upregulated
      expression of alphaSMA and collagen. As activated HSCs may be a suitable target
      for HCC therapy and targeting these cells rather than the HCC cells may result in
      a greater response. Collectively, our studies indicate for the first time the
      detailed mechanism of activation of HSC through TRPC6 signaling and thus being a
      promising therapeutic target.

PMID- 25845498
TI  - GPR4 decreases B16F10 melanoma cell spreading and regulates focal adhesion
      dynamics through the G13/Rho signaling pathway.
AB  - The effect of acidosis, a biochemical hallmark of the tumor microenvironment, on
      cancer progression and metastasis is complex. Both pro- and anti-tumorigenic
      effects of acidosis have been reported and the acidic microenvironment has been
      exploited for specific delivery of drugs, imaging agents, and genetic constructs
      into tumors. In this study we investigate the spreading and focal adhesion of
      B16F10 melanoma cells that are genetically engineered to overexpress the pH
      sensing G protein-coupled receptor GPR4. By using cell attachment assays we found
      that GPR4 overexpression delayed cell spreading and altered the spatial
      localization of dynamic focal adhesion complex, such as the localization of
      phosphorylated focal adhesion kinase (FAK) and paxillin, at acidic pH. The
      potential G-protein and downstream signaling pathways that are responsible for
      these effects were also investigated. By using the Rho inhibitor CT04 (C3
      transferase), the Rho-associated kinase (ROCK) inhibitors Y27632 and thiazovivin,
      the myosin light chain kinase (MLCK) inhibitor staurosporine or a G12/13
      inhibitory construct, cell spreading was restored whereas the inhibition and
      activation of the Gq and Gs pathways had little or no effect. Altogether our
      results indicate that through the G12/13/Rho signaling pathway GPR4 modulates
      focal adhesion dynamics and reduces cell spreading and membrane ruffling. 

PMID- 25845499
TI  - Preservation of high glycolytic phenotype by establishing new acute lymphoblastic
      leukemia cell lines at physiologic oxygen concentration.
AB  - Cancer cells typically exhibit increased glycolysis and decreased mitochondrial
      oxidative phosphorylation, and they continue to exhibit some elevation in
      glycolysis even under aerobic conditions. However, it is unclear whether cancer
      cell lines employ a high level of glycolysis comparable to that of the original
      cancers from which they were derived, even if their culture conditions are
      changed to physiologically relevant oxygen concentrations. From three childhood
      acute lymphoblastic leukemia (ALL) patients we established three new pairs of
      cell lines in both atmospheric (20%) and physiologic (bone marrow level, 5%)
      oxygen concentrations. Cell lines established in 20% oxygen exhibited lower
      proliferation, survival, expression of glycolysis genes, glucose consumption, and
      lactate production. Interestingly, the effects of oxygen concentration used
      during cell line initiation were only partially reversible when established cell
      cultures were switched from one oxygen concentration to another for eight weeks.
      These observations indicate that ALL cell lines established at atmospheric oxygen
      concentration can exhibit relatively low levels of glycolysis and these levels
      are semi-permanent, suggesting that physiologic oxygen concentrations may be
      needed from the time of cell line initiation to preserve the high level of
      glycolysis commonly exhibited by leukemias in vivo. 

PMID- 25845500
TI  - Identification and fine mapping of quantitative trait loci for the number of
      vascular bundle in maize stem.
AB  - Studies that investigated the genetic basis of source and sink related traits
      have been widely conducted. However, the vascular system that links source and
      sink received much less attention. When maize was domesticated from its wild
      ancestor, teosinte, the external morphology has changed dramatically; however,
      less is known for the internal anatomy changes. In this study, using a large
      maize-teosinte experimental population, we performed a high-resolution
      quantitative trait locus (QTL) mapping for the number of vascular bundle in the
      uppermost internode of maize stem. The results showed that vascular bundle number
      is dominated by a large number of small-effect QTLs, in which a total of 16 QTLs
      that jointly accounts for 52.2% of phenotypic variation were detected, with no
      single QTL explaining more than 6% of variation. Different from QTLs for typical
      domestication traits, QTLs for vascular bundle number might not be under
      directional selection following domestication. Using Near Isogenic Lines (NILs)
      developed from heterogeneous inbred family (HIF), we further validated the effect
      of one QTL qVb9-2 on chromosome 9 and fine mapped the QTL to a 1.8-Mb physical
      region. This study provides important insights for the genetic architecture of
      vascular bundle number in maize stem and sets basis for cloning of qVb9-2. 

PMID- 25845501
TI  - Physicochemical control of bacterial and protist community composition and
      diversity in Antarctic sea ice.
AB  - Due to climate change, sea ice experiences changes in terms of extent and
      physical properties. In order to understand how sea ice microbial communities are
      affected by changes in physicochemical properties of the ice, we used 454
      sequencing of 16S and 18S rRNA genes to examine environmental control of
      microbial diversity and composition in Antarctic sea ice. We observed a high
      diversity and richness of bacteria, which were strongly negatively correlated
      with temperature and positively with brine salinity. We suggest that bacterial
      diversity in sea ice is mainly controlled by physicochemical properties of the
      ice, such as temperature and salinity, and that sea ice bacterial communities are
      sensitive to seasonal and environmental changes. For the first time in Antarctic
      interior sea ice, we observed a strong eukaryotic dominance of the dinoflagellate
      phylotype SL163A10, comprising 63% of the total sequences. This phylotype is
      known to be kleptoplastic and could be a significant primary producer in sea ice.
      We conclude that mixotrophic flagellates may play a greater role in the sea ice
      microbial ecosystem than previously believed, and not only during the polar night
      but also during summer when potential food sources are abundant. 

PMID- 25845502
TI  - Novel selective inhibitor of Leishmania (Leishmania) amazonensis arginase.
AB  - Arginase is a glycosomal enzyme in Leishmania that is involved in polyamine and
      trypanothione biosynthesis. The central role of arginase in Leishmania
      (Leishmania) amazonensis was demonstrated by the generation of two mutants: one
      with an arginase lacking the glycosomal addressing signal and one in which the
      arginase-coding gene was knocked out. Both of these mutants exhibited decreased
      infectivity. Thus, arginase seems to be a potential drug target for Leishmania
      treatment. In an attempt to search for arginase inhibitors, 29 derivatives of the
      [1,2,4]triazolo[1,5-a]pyrimidine system were tested against Leishmania
      (Leishmania) amazonensis arginase in vitro. The [1,2,4]triazolo[1,5-a]pyrimidine
      scaffold containing R1  = CF3 exhibited greater activity against the arginase
      rather than when the substituent R1  = CH3 in the 2-position. The novel compound
      2-(5-methyl-2-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyrimidin-7
      yl)hydrazinecarbothioamide (30) was the most potent, inhibiting arginase by a non
      competitive mechanism, with the Ki and IC50 values for arginase inhibition
      estimated to be 17 +/- 1 MUm and 16.5 +/- 0.5 MUm, respectively. These results
      can guide the development of new drugs against leishmaniasis based on
      [1,2,4]triazolo[1,5-a]pyrimidine derivatives targeting the arginase enzyme. 

PMID- 25845503
TI  - Accuracy of thyroid nodule sonography for the detection of thyroid cancer in
      children: systematic review and meta-analysis.
AB  - INTRODUCTION: Thyroid ultrasound (US) is a widely used tool for evaluating
      thyroid nodules. Various US features have been suggested as predictors of thyroid
      cancer in children. OBJECTIVE: To conduct a systematic review and meta-analysis
      to assess the diagnostic accuracy of different thyroid US features in detecting
      thyroid cancer in children. METHODS: We searched multiple online databases for
      cohort studies that enrolled paediatric patients with thyroid nodules (age <21
      years) and evaluated the accuracy of 12 relevant ultrasound features. Diagnostic
      measures were pooled across studies using a random effects model. RESULTS: The
      search strategy yielded 1199 citations, of which 12 studies met the predefined
      inclusion criteria (750 nodules). The prevalence of thyroid cancer was 27.2%
      (40.8% in patients with a history of radiation exposure and 23.2% in patients
      without a history of exposure to radiation). The most common cancer was papillary
      thyroid cancer (86.7%). The presence of internal calcifications and enlarged
      cervical lymph nodes were the US features with the highest likelihood ratio [4.46
      (95% CI: 1.87-10.64) and 4.96 (95% CI: 2.01-12.24), respectively] for thyroid
      cancer. A cystic nodule was the feature with highest likelihood ratio for benign
      nodules [1.96 (95% CI: 0.87-4.43)]. CONCLUSION: Thyroid US features are not
      highly accurate predictors of benign or malignant aetiology of thyroid nodules in
      children. Internal calcification may predict malignancy, and cystic appearance
      may suggest benign aetiology.

PMID- 25845504
TI  - Is methylisothiazolinone contact allergy a risk factor for polysensitization?

PMID- 25845505
TI  - Acute kidney injury in severe sepsis: pathophysiology, diagnosis, and treatment
      recommendations.
AB  - OBJECTIVE: To review the unique pathophysiology of sepsis-induced acute kidney
      injury (AKI) and highlight the relevant aspects of the Kidney Disease: Improving
      Global Outcomes (KDIGO) Clinical Practice Guideline for Acute Kidney Injury that
      may apply to veterinary patients. DATA SOURCES: Electronic search of MEDLINE
      database. HUMAN DATA SYNTHESIS: Sepsis-induced AKI is diagnosed in up to 47% of
      human ICU patients and is seen as a major public health concern associated with
      increased mortality and increased progression to chronic kidney disease (CKD).
      Consensus criteria for the definition and classification of AKI has allowed for
      accurate description of the epidemiology of patients with AKI. AKI develops from
      a complex relationship between the initial insult and activation of inflammation
      and coagulation. In contrast to the traditional view, clinical and experimental
      data dispute the role of renal ischemia-reperfusion in the development of sepsis
      induced AKI. Renal tubular dysfunction with activation of the tubuloglomerular
      feedback mechanism appears to be a crucial contributor to sepsis-induced AKI.
      Furosemide and n-acetylcysteine (NAC) do not appear to be helpful in the
      treatment of AKI. Hydroxyethyl starches (HES), dopamine, and supraphysiological
      concentrations of chloride are harmful in patients with AKI. VETERINARY DATA
      SYNTHESIS: Community and hospital-acquired AKI is a significant factor affecting
      survival in critical ill patients. Sepsis-induced AKI occurs in 12% of dogs with
      abdominal sepsis and is an important contributor to mortality. Early detection of
      AKI in hospitalized patients currently offers the best opportunity to improve
      patient outcome. The use of urinary biomarkers to diagnose early AKI should be
      evaluated in critical care patients. CONCLUSION: Veterinary clinical trials
      comparing treatment choices with the development of AKI are needed to make
      evidence-based recommendations for the prevention and treatment of AKI.

PMID- 25845506
TI  - Retrospective evaluation of risk factors and outcome predictors in cats with
      diabetic ketoacidosis (1997-2007): 93 cases.
AB  - OBJECTIVES: To determine risk factors and outcome predictors in cats with
      diabetic ketoacidosis (DKA). DESIGN: Retrospective study. Inclusion in the DKA
      group required blood glucose concentration > 13.9 mmol/L (250 mg/dL), venous pH <
      7.35, and urine or serum acetoacetate concentration greater than 1.5 mmol/L (15
      mg/dL). Signalment and weight were recorded in all cats with uncomplicated
      diabetes mellitus (DM) without DKA and in all other nondiabetic cats examined
      during the study period. Clinicopathologic variables, concurrent disorders, and
      initial insulin intravenous (IV) continuous-rate infusion (CRI) concentration of
      1.1 or 2.2 U/kg/240 mL bag of 0.9% NaCl, were examined for a possible association
      with outcome. SETTING: University teaching hospital. ANIMALS: Ninety-three cats
      with DKA, 682 cats with uncomplicated DM, and 16,926 cats without DM or DKA.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Cats with DKA were younger
      (median age 9.4 years; range, 1-17.9 years) than cats with uncomplicated DM
      (median 11.6 years; range 0.7-19.5 years, P < 0.0003). Siamese cats were
      overrepresented in the DKA group compared to the uncomplicated DM or nondiabetic
      group (P = 0.038 and P = 0.01, respectively). Poor outcome (defined as death due
      to disease or by euthanasia) in 36 cats with DKA (39%) was associated with
      increased initial creatinine, BUN, total serum magnesium, and total bilirubin
      concentrations (P = 0.007, P = 0.005, P = 0.03, P = 0.03, respectively). Cats
      treated with a higher concentration of insulin were less likely to have a poor
      outcome compared to cats treated with a lower concentration of insulin (odds
      ratio 0.14, 95% confidence interval 0.02-1.16, P = 0.02). CONCLUSIONS: Cats with
      DKA are more likely to be Siamese than cats with uncomplicated DM. Poor outcome
      of cats with DKA is associated with increased initial creatinine, BUN, total
      magnesium, and total bilirubin concentrations. Good outcome was associated with a
      higher concentration of IV insulin CRI.

PMID- 25845514
TI  - CHILD Syndrome: Successful Treatment of Skin Lesions with Topical
      Simvastatin/Cholesterol Ointment--A Case Report.
AB  - CHILD syndrome is a rare X-linked dominant condition that presents with
      congenital hemidysplasia, Ichthyosiform erythroderma, and limb defects in
      affected patients. We report the case of a 10-year-old girl treated with topical
      simvastatin and cholesterol ointment, after which her skin lesions significantly
      improved within the first 30 days of treatment. 

PMID- 25845515
TI  - Using discussion groups as a strategy for postgraduate implant dentistry students
      to reflect.
AB  - INTRODUCTION: More than undergraduates, postgraduate students have the day-to-day
      clinical experience to reflect upon. Nevertheless, reflection in postgraduate
      dental education is less well studied. Hence, the purpose was to investigate the
      attitude towards reflection and the content of reflections in postgraduate
      implant dentistry education in the UK and Belgium. MATERIALS AND METHODS: To
      investigate the attitude towards reflection, a questionnaire was administered to
      the 10 postgraduates at UCL Eastman Dental Institute (EDI) and 6 postgraduates at
      Ghent University (UGent). Additionally, students were invited to attend two
      reflective sessions (60-90 minutes). The sessions' audio recordings were
      transcribed and analysed using a thematic approach. RESULTS: In total, 16
      postgraduate implant dentistry students participated. Although the majority
      reported prior experience with reflection, there was variation in the provided
      definitions of reflection. EDI students agreed with reflection being beneficial
      for professional development/clinical reasoning and were positive about
      discussing clinical experiences in groups, but were divided about
      individual/group reflections. Their UGent counterparts were more indecisive
      (=neutral), but were positive about discussing clinical experiences. Thematic
      analysis identified recurring themes as individual learning process, learning and
      clinical experiences, attitude towards implant dentistry and course programme.
      EDI postgraduates' reflections focussed on specific clinical situations, while
      UGent postgraduates' reflections described general considerations. CONCLUSION:
      Although students/professionals often report to reflect, it is not clear
      whether/how they actually reflect, due to the all-purpose word reflection has
      become. A strategy, using group discussions along with supervision/guidance in
      how to reflect, demonstrated to expand clinical reasoning into reflections about
      postgraduate students' clinical actions and professional growth.

PMID- 25845516
TI  - Nickel-catalysed P-C bond formation via P-H/C-CN cross coupling reactions.
AB  - Nickel-catalysed P-H/C-CN cross coupling reactions take place efficiently under
      mild reaction conditions affording the corresponding sp(2)C-P bonds. This
      transformation provides a convenient method for the preparation of arylphosphines
      and arylphosphine oxides from the readily available P-H compounds and
      arylnitriles. 

PMID- 25845517
TI  - Theoretical study on reaction mechanisms of nitrite reduction by copper nitrite
      complexes: toward understanding and controlling possible mechanisms of copper
      nitrite reductase.
AB  - Using density functional theory, we studied denitrification reaction mechanisms
      of copper adducts of tris(pyrazolyl)methane and hydrotris(pyrazolyl)borate models
      of a copper nitrite reductase (Cu-NiR), and herein propose several possible
      reaction pathways, including some parts that have never been examined previously.
      Because electron and proton transfer reactions participate in the enzymatic
      cycles of Cu-NiR, the Gibbs energy of a proton in solution, G(H(+)), and the
      redox potential, Eredox, of the model Cu-NiR are also evaluated. Although the
      pathway where a nitrite is provided as HNO2 is energetically preferable, a well
      known reaction pathway passing through the resting state with an active site
      occupied by a water molecule where nitrite is provided as NO2(-) is the main
      recognized pathway under normal conditions. These features do not change whether
      the electron transfer occurs before production of NO or not. However, our results
      suggest that the pathway involving HNO2 might become dominant under low pH
      conditions in conjunction with experimental results. 

PMID- 25845518
TI  - Bicarbonate Therapy in End-Stage Renal Disease: Current Practice Trends and
      Implications.
AB  - Management of metabolic acidosis covers the entire spectrum from oral bicarbonate
      therapy and dietary modifications in chronic kidney disease to delivery of high
      doses of bicarbonate-based dialysate during maintenance haemodialysis (MHD). Due
      to the gradual depletion of the body's buffers and rapid repletion during MHD,
      many potential problems arise as a result of our current treatment paradigms.
      Several studies have given rise to conflicting data about the adverse effects of
      our current practice patterns in MHD. In this review, we will describe the
      pathophysiology and consequences of metabolic acidosis and its therapy in CKD and
      ESRD, and discuss current evidence supporting a more individualized approach for
      bicarbonate therapy in MHD. 

PMID- 25845519
TI  - A retrospective study of factors which determine a negative blood culture in
      Cambodian children diagnosed with enteric fever.
AB  - BACKGROUND: Blood cultures are used to confirm a diagnosis of enteric fever but
      reported sensitivities can be as low as 40%. AIMS: To determine the factors
      associated with a negative blood culture in Cambodian children with suspected
      enteric fever. METHODS: In a retrospective study of hospitalised Cambodian
      children given a discharge diagnosis of enteric fever, the following factors
      associated with a negative blood culture were analysed: age, blood culture
      volume, prior antibiotic therapy, duration of illness and disease severity.
      RESULTS: In 227 hospitalised Cambodian children with a discharge diagnosis of
      enteric fever, it was confirmed in 70% by a positive blood culture. There was no
      association between a negative blood culture and younger age, lower blood volumes
      for culture, prior antibiotic therapy, a late presentation or milder disease.
      CONCLUSIONS: Although blood culture sensitivity was higher than expected,
      alternative simple, rapid and sensitive tests are needed for diagnosing enteric
      fever.

PMID- 25845520
TI  - Chromosome structure deficiencies in MCPH1 syndrome.
AB  - Mutations in the MCPH1 gene result in primary microcephaly in combination with a
      unique cellular phenotype of defective chromosome condensation. MCPH1 patient
      cells display premature chromosome condensation in G2 phase of the cell cycle and
      delayed decondensation in early G1 phase, observable as an increased proportion
      of cells with prophase-like appearance. MCPH1 deficiency thus appears to uncouple
      the chromosome cycle from the coordinated series of events that take place during
      mitosis such as some phases of the centrosome cycle and nuclear envelope
      breakdown. Here, we provide a further characterization of the effects of MCPH1
      loss-of-function on chromosome morphology. In comparison to healthy controls,
      chromosomes of MCPH1 patients are shorter and display a pronounced coiling of
      their central chromatid axes. In addition, a substantial fraction of metaphase
      chromosomes shows apparently unresolved chromatids with twisted appearance. The
      patient chromosomes also showed signs of defective centromeric cohesion, which
      become more apparent and pronounced after harsh hypotonic conditions. Taking
      together, the observed alterations indicate additional so far unknown functions
      of MCPH1 during chromosome shaping and dynamics. 

PMID- 25845521
TI  - An improved isolation technique for shaggy brachiocephalic artery and aortic arch
      replacement.
AB  - A mobile plaque in the ascending and transverse aorta increases the risk of
      cerebral infarction during treatment of an arch aneurysm. A previous report
      described an isolation technique for replacing the ascending and transverse aorta
      with a mobile atheroma by selective hypothermic antegrade cerebral perfusion
      (Shiiya et al., Ann Thorac Surg 72:1401-1402, 2001). Here, we present an improved
      isolation technique for more severe conditions, such as shaggy aorta and shaggy
      brachiocephalic artery, in two patients. First, we anastomosed both axillae
      arteries with grafts and placed drainage cannulae in the superior and inferior
      venae cavae prior to filling the cardio-pulmonary bypass system with blood. Next,
      we cannulated the right common carotid artery and selective cerebral perfusion
      was started prior to cannulation and perfusion of the left common carotid artery.
      Systemic perfusion was then initiated through the axillae grafts. Both patients
      who underwent this procedure recovered without neurologic complications. 

PMID- 25845522
TI  - Suicide Ideations, Suicide Attempts, and Completed Suicide in Persons with
      Pathological Gambling and Their First-Degree Relatives.
AB  - We examined the relationship between suicidal ideations and attempts in 95
      probands with pathological gambling (PG), 91 controls, and 1075 first-degree
      relatives. The results were analyzed using logistic regression with generalized
      estimating equations. Thirty-four PG probands (35.8%) and 4 controls (4.4%) had
      attempted suicide (OR = 12.12, p < .001); in 13 probands, the attempt occurred
      before PG onset. Lifetime suicidal ideations occurred in 60 PG probands (63.2%)
      and 12 controls (13.2%) (OR = 11.29, p < .001). Suicidality in PG probands is a
      marker of PG severity and is associated with greater psychiatric comorbidity.
      Offspring of PG probands had significantly higher rates of suicide attempts than
      control offspring. 

PMID- 25845524
TI  - Craniofacial asymmetry in non-syndromic orthodontic subjects: clinical and
      postural evaluation.
AB  - OBJECTIVE: The aim of this study was to evaluate the possible influence of a
      malocclusion pattern on a patient's posture. METHODS: Patients affected by
      symmetric malocclusion or malocclusion with mild to moderate non-syndromic
      craniofacial asymmetry were submitted to a clinical and X-ray evaluation.
      Subjects with symmetric skeletal class I were used as the control group.
      Evaluation of differences in postural pattern was performed using
      rasterstereography. RESULTS: Statistical analysis (t-test) was performed on 61
      patients divided in homogeneous subgroups. The results show a pelvic torsion
      angle of 1.08 degrees  + 3.00 degrees  (P = 0.0023) (normal value (NV) = 0.0-1.9
      degrees ) in subjects presenting skeletal class II z asymmetry (control group:
      1.17 degrees  +/- 1.25 degrees , not significant (NS)). CONCLUSIONS: The present
      study shows evidence of a relationship between malocclusion and spinal posture. A
      better understanding of the relationship between malocclusion and posture may
      help in planning a multidisciplinary approach that could involve other
      specialists.

PMID- 25845525
TI  - Increased expression of neuropilin 1 is associated with epithelial ovarian
      carcinoma.
AB  - Neuropilin 1 (NRP1) is a transmembrane glycoprotein, which interacts with
      vascular endothelial growth factor to prevent tumor cell apoptosis and to
      regulate angiogenesis. However, the precise role of NRP1 in epithelial ovarian
      carcinoma (EOC) remains to be elucidated. The present study aimed to determine
      the association between NRP1 and EOC. The expression of NRP1 in ovarian cancer
      and normal ovarian epithelial tissues was investigated by immunofluorescence,
      reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and
      western blotting. The association between the expression of NRP1 with the
      development of ovarian cancer, clinicopathological characteristics and survival
      were also analyzed. The results from immunofluorescence, RT-qPCR and western blot
      analysis demonstrated that NRP1 exhibited significant upregulation in EOC
      compared with normal ovarian epithelial specimens (P<0.05). The positive
      expression of NRP1 was higher in cancer tissues at an advanced International
      Federation of Gynecology and Obstetrics stage, and in cancer tissues with lymph
      node metastasis and distant metastasis compared with that in cancer tissues
      without lymph node or distant metastasis (P<0.05). Higher NRP1 expression
      strongly predicted a shorter survival time (P<0.001). The present findings
      suggested that increased NRP1 expression may be associated with the development
      of EOC. Therefore, NRP1 could be used as a valuable prognostic marker as well as
      a potential molecular therapy target for ovarian cancer patients.

PMID- 25845526
TI  - The current preference for the immuno-analytical ELISA method for quantitation of
      steroid hormones (endocrine disruptor compounds) in wastewater in South Africa.
AB  - The availability of national test centers to offer a routine service for analysis
      and quantitation of some selected steroid hormones [natural estrogens (17-beta
      estradiol, E2; estrone, E1; estriol, E3), synthetic estrogen (17-alpha
      ethinylestradiol, EE2), androgen (testosterone), and progestogen (progesterone)]
      in wastewater matrix was investigated; corresponding internationally used
      chemical- and immuno-analytical test methods were reviewed. The enzyme-linked
      immunosorbent assay (ELISA) (immuno-analytical technique) was also assessed for
      its suitability as a routine test method to quantitate the levels of these
      hormones at a sewage/wastewater treatment plant (WTP) (Darvill, Pietermaritzburg,
      South Africa), over a 2-year period. The method performance and other relevant
      characteristics of the immuno-analytical ELISA method were compared to the
      conventional chemical-analytical methodology, like gas/liquid chromatography-mass
      spectrometry (GC/LC-MS), and GC-LC/tandem mass spectrometry (MSMS), for
      quantitation of the steroid hormones in wastewater and environmental waters. The
      national immuno-analytical ELISA technique was found to be sensitive (LOQ 5 ng/L,
      LOD 0.2-5 ng/L), accurate (mean recovery 96%), precise (RSD 7-10%), and cost
      effective for screening and quantitation of these steroid hormones in wastewater
      and environmental water matrix. A survey of the most current international
      literature indicates a fairly equal use of the LC-MS/MS, GC-MS/MS (chemical
      analytical), and ELISA (immuno-analytical) test methods for screening and
      quantitation of the target steroid hormones in both water and wastewater matrix.
      Internationally, the observed sensitivity, based on LOQ (ng/L), for the steroid
      estrogens E1, E2, EE2, is, in decreasing order: LC-MSMS (0.08-9.54) > GC-MS (1) >
      ELISA (5) (chemical-analytical > immuno-analytical). At the national level, the
      routine, unoptimized chemical-analytical LC-MSMS method was found to lack the
      required sensitivity for meeting environmental requirements for steroid hormone
      quantitation. Further optimization of the sensitivity of the chemical-analytical
      LC-tandem mass spectrometry methods, especially for wastewater screening, in
      South Africa is required. Risk assessment studies showed that it was not
      practical to propose standards or allowable limits for the steroid estrogens E1,
      E2, EE2, and E3; the use of predicted-no-effect concentration values of the
      steroid estrogens appears to be appropriate for use in their risk assessment in
      relation to aquatic organisms. For raw water sources, drinking water, raw and
      treated wastewater, the use of bioassays, with trigger values, is a useful
      screening tool option to decide whether further examination of specific endocrine
      activity may be warranted, or whether concentrations of such activity are of low
      priority, with respect to health concerns in the human population. The
      achievement of improved quantitation limits for immuno-analytical methods, like
      ELISA, used for compound quantitation, and standardization of the method for
      measuring E2 equivalents (EEQs) used for biological activity (endocrine: e.g.,
      estrogenic) are some areas for future EDC research.

PMID- 25845527
TI  - Thermodynamic-based retention time predictions of endogenous steroids in
      comprehensive two-dimensional gas chromatography.
AB  - This work evaluates the application of a thermodynamic model to comprehensive two
      dimensional gas chromatography (GC * GC) coupled with time-of-flight mass
      spectrometry for anabolic agent investigation. Doping control deals with hundreds
      of drugs that are prohibited in sports. Drug discovery in biological matrices is
      a challenging task that requires powerful tools when one is faced with the
      rapidly changing designer drug landscape. In this work, a thermodynamic model
      developed for the prediction of both primary and secondary retention times in GC
      * GC has been applied to trimethylsilylated hydroxyl (O-TMS)- and methoxime
      trimethylsilylated carbonyl (MO-TMS)-derivatized endogenous steroids. This model
      was previously demonstrated on a pneumatically modulated GC * GC system, and is
      applied for the first time to a thermally modulated GC * GC system. Preliminary
      one-dimensional experiments allowed the calculation of thermodynamic parameters
      (DeltaH, DeltaS, and DeltaC p ) which were successfully applied for the
      prediction of the analytes' interactions with the stationary phases of both the
      first-dimension column and the second-dimension column. The model was able to
      predict both first-dimension and second-dimension retention times with high
      accuracy compared with the GC * GC experimental measurements. Maximum differences
      of -8.22 s in the first dimension and 0.4 s in the second dimension were
      encountered for the O-TMS derivatives of 11beta-hydroxyandrosterone and 11
      ketoetiocholanolone, respectively. For the MO-TMS derivatives, the largest
      discrepancies were from testosterone (9.65 ) for the first-dimension retention
      times and 11-keto-etiocholanolone (0.4 s) for the second-dimension retention
      times.

PMID- 25845528
TI  - Hypermethylation of the tumor-suppressor cell adhesion molecule 1 in human
      papillomavirus-transformed cervical carcinoma cells.
AB  - Epigenetic modification at CpG islands located on the promoter regions of tumor
      suppressor genes has been associated with tumor development in many human
      cancers. Our study showed that the cell adhesion molecule 1 (CADM1) is
      downregulated in human papillomavirus (HPV)-infected cervical cancer cell lines
      via its hypermethylation and demethylation using 5-aza-2'-deoxycyticine (5-aza
      dC) restored the expression of CADM1 protein. Overexpression of CADM1 inhibited
      cell proliferation. p53 was involved in the regulation of CADM1. Our results
      demonstrate that epigenetic alteration of CADM1 was more frequent in HPV-positive
      cervical cancers and that restoration of CADM1 expression may be a potential
      strategy for cervical cancer therapy. 

PMID- 25845529
TI  - The over-pruning hypothesis of autism.
AB  - This article outlines the over-pruning hypothesis of autism. The hypothesis
      originates in a neurocomputational model of the regressive sub-type (Thomas,
      Knowland & Karmiloff-Smith, 2011a, 2011b). Here we develop a more general version
      of the over-pruning hypothesis to address heterogeneity in the timing of
      manifestation of ASD, including new computer simulations which reconcile the
      different observed developmental trajectories (early onset, late onset,
      regression) via a single underlying atypical mechanism; and which show how
      unaffected siblings of individuals with ASD may differ from controls either by
      inheriting a milder version of the pathological mechanism or by co-inheriting the
      risk factors without the pathological mechanism. The proposed atypical mechanism
      involves overly aggressive synaptic pruning in infancy and early childhood, an
      exaggeration of a normal phase of brain development. We show how the hypothesis
      generates novel predictions that differ from existing theories of ASD including
      that (1) the first few months of development in ASD will be indistinguishable
      from typical, and (2) the earliest atypicalities in ASD will be sensory and motor
      rather than social. Both predictions gain cautious support from emerging
      longitudinal studies of infants at-risk of ASD. We review evidence consistent
      with the over-pruning hypothesis, its relation to other current theories
      (including C. Frith's under-pruning proposal; C. Frith, 2003, 2004), as well as
      inconsistent data and current limitations. The hypothesis situates causal
      accounts of ASD within a framework of protective and risk factors (Newschaffer et
      al., 2012); clarifies different versions of the broader autism phenotype (i.e.
      the implication of observed similarities between individuals with autism and
      their family members); and integrates data from multiple disciplines, including
      behavioural studies, neuroscience studies, genetics, and intervention studies.

PMID- 25845530
TI  - The influence of a peer-based HIV prevention intervention on conversation about
      HIV prevention among people who inject drugs in Baltimore, Maryland.
AB  - STEP into Action assessed the efficacy of a peer-based HIV prevention
      intervention in reducing HIV risk behaviors among people who inject drugs (PWIDs)
      in Baltimore. This analysis examined the effect of the intervention on the change
      in frequency of conversation about HIV prevention topics over time. 114
      participants were randomized into an experimental and 113 into a control group.
      Data was collected prospectively at 6, 12, and 18 months. The experimental group
      talked more frequently about HIV prevention topics compared to the control group
      at 6-month visit. At 18 months relative risk ratios (RRR) remained statistically
      significant for conversation about the danger of needle sharing (RRR = 3.21) and
      condom use (RRR = 2.81). The intervention resulted in an increased conversation
      about HIV prevention among PWIDs, but the sustainability past 6 months remained a
      challenge; suggesting that interventions should be designed to constantly
      reinforce communication about HIV prevention among PWIDs. 

PMID- 25845531
TI  - Understanding Consistent Condom Use Among Homeless Men Who Have Sex with Women
      and Engage in Multiple Sexual Partnerships: A Path Analysis.
AB  - Consistent condom use is the main strategy aimed at preventing individuals from
      acquiring HIV through sexual intercourse. The mechanism of consistent condom use
      among a high-risk homeless subpopulation-homeless men who have sex with women and
      also engage in multiple sexual partnerships-remains unclear. This study
      identified 182 homeless men who engaged in multiple sexual partnerships from a
      representative sample of homeless men, who self-identified as heterosexual, using
      meal line services in Downtown Los Angeles' Skid Row area. Information such as
      participants' condom use psychosocial correlates, sexual risk behaviors, and
      social network characteristics were collected. Results suggested that condom
      efficacy is a potential intervening mechanism through which condom attitudes
      (beta = -0.199; p = 0.005) and depression (beta = -0.156; p = 0.029) are
      associated with an individual's consistent condom use. Having more network
      members with whom participants talked about HIV prevention (beta = 0.051; p =
      0.006) was also found to be associated with an individual's consistent condom
      use. HIV prevention programs should focus on increasing their condom efficacy to
      help reduce HIV risks among this vulnerable homeless subpopulation. 

PMID- 25845532
TI  - Internal heavy atom effects in phenothiazinium dyes: enhancement of intersystem
      crossing via vibronic spin-orbit coupling.
AB  - The effect of substituting the intra-cyclic sulphur of thionine by oxygen
      (oxonine) and selenium (selenine) on the intersystem crossing (ISC) efficiency
      has been studied using high level quantum mechanical methods. The ISC rate
      constants are considerably increased when going from O towards Se while the
      fluorescence rate constants remain unchanged. For the three dyes, all accessible
      ISC channels are driven by vibronic spin-orbit coupling (SOC) between pipi*
      states. The interplay between the ground and low-lying excited states has been
      investigated in order to determine the dominant relaxation pathways. In oxonine
      the relaxation to the ground state after photoexcitation in water proceeds
      essentially via fluorescence from the S1(piHpiL*) bright state (kF = 2.10 * 10(8)
      s(-1)), in agreement with the high experimental fluorescence quantum yield. In
      aqueous solution of thionine, the ISC rate constant (kISC ~ 1 * 10(9) s(-1)) is
      one order of magnitude higher than fluorescence (kF = 1.66 * 10(8) s(-1)) which
      is consistent with its high triplet quantum yield observed in water (phiT =
      0.53). Due to a stronger vibronic SOC in selenine, the ISC rate is very high
      (kISC ~ 10(10) s(-1)) and much faster than fluorescence (kF = 1.59 * 10(8) s(
      1)). This suggests selenine-based dyes as very efficient triplet
      photosensitizers. 

PMID- 25845534
TI  - Medicalization of the Post-Museum: Interactivity and Diagnosis at the Brain and
      Cognition Exhibit.
AB  - The introduction of digital games and simulations into science museums has
      prompted excitement about a new "post-museum" pedagogy emphasizing
      egalitarianism, interactivity, and personalized approaches to learning. However,
      many post-museums of science, this article aims to show, enact rhetorical
      performances that lead visitors to narrowly targeted answers and hide the
      authority of the expert in a play of tactile and affective activities, thus
      operating in opposition to many of the basic ideals of the post-museum. The Brain
      and Cognition Exhibit at the Hong Kong Science Museum serves as a case study for
      how a post-museum exhibit, through embracing interactivity and visitor-centered
      tasks, becomes a site where science is tested on and performed through visitors'
      bodies such that institutional prescriptions are applied. Visitors are not merely
      encouraged at this exhibit to learn about the brain through doing but are trained
      to see functional and dysfunctional brains and to then diagnose themselves and
      their children by playing games and taking brain-measurement tests. As a result,
      the interactive engagement of the exhibit creates a new space of public
      medicalization. Reflections and suggestions are offered at the end of the
      article. 

PMID- 25845535
TI  - A sensitive and high throughput bacterial luminescence assay for assessing
      aquatic toxicity--the BLT-Screen.
AB  - Bioassays using naturally luminescent bacteria are commonly used to assess the
      toxicity of environmental contaminants, detected by a decrease in luminescence.
      Typically, this has involved the use of commercial test kits such as Microtox and
      ToxScreen. These commercial assays, however, have limitations for routine
      environmental monitoring, including the need for specialized equipment, a low
      throughput and high on-going costs. There is therefore a need to develop a
      bacteria bioassay that is sensitive, high-throughput and cost effective. This
      study presents the development and application of the BLT-Screen (Bacterial
      Luminescence Toxicity Screen), a 96-well plate bioassay using Photobacterium
      leiognathi. During development of the method, the concentration of the phosphate
      buffer in the experimental medium was adjusted to maximize the sensitivity of the
      assay, and protocols for analyzing both solid-phase extracts and raw water
      samples were established. A range of organic compounds and metals were analyzed
      in the assay, as well as extracts of various water samples, including drinking
      water, wastewater effluent and river water. The IC50 values of the organic
      compounds and metals tested in the BLT-Screen were comparable to previously
      published ToxScreen and Microtox data. In addition, the assay was sensitive
      enough to detect toxicity in all water types tested, and performed equally well
      for both solid-phase extracts and raw water samples. The BLT-Screen therefore
      presents a cost-effective, sensitive and high throughput method for testing the
      toxicity of environmental contaminants in a range of water types that has
      widespread applications for research, as well as for routine monitoring and
      operation of wastewater and drinking water plants. 

PMID- 25845536
TI  - Replicating poxviruses for human cancer therapy.
AB  - Naturally occurring oncolytic viruses are live, replication-proficient viruses
      that specifically infect human cancer cells while sparing normal cell
      counterparts. Since the eradication of smallpox in the 1970s with the aid of
      vaccinia viruses, the vaccinia viruses and other genera of poxviruses have shown
      various degrees of safety and efficacy in pre-clinical or clinical application
      for human anti-cancer therapeutics. Furthermore, we have recently discovered that
      cellular tumor suppressor genes are important in determining poxviral oncolytic
      tropism. Since carcinogenesis is a multi-step process involving accumulation of
      both oncogene and tumor suppressor gene abnormalities, it is interesting that
      poxvirus can exploit abnormal cellular tumor suppressor signaling for its
      oncolytic specificity and efficacy. Many tumor suppressor genes such as p53, ATM,
      and RB are known to play important roles in genomic fidelity/maintenance. Thus,
      tumor suppressor gene abnormality could affect host genomic integrity and likely
      disrupt intact antiviral networks due to accumulation of genetic defects, which
      would in turn result in oncolytic virus susceptibility. This review outlines the
      characteristics of oncolytic poxvirus strains, including vaccinia, myxoma, and
      squirrelpox virus, recent progress in elucidating the molecular connection
      between oncogene/tumor suppressor gene abnormalities and poxviral oncolytic
      tropism, and the associated preclinical/clinical implications. I would also like
      to propose future directions in the utility of poxviruses for oncolytic
      virotherapy. 

PMID- 25845538
TI  - Multiple roles of a putative vacuolar protein sorting associated protein 74,
      FgVPS74, in the cereal pathogen Fusarium graminearum.
AB  - Fusarium graminearum, a member of the F. graminearum species complex, is a
      filamentous ascomycetous group that causes serious diseases in cereal crops. A
      screen of insertional mutants of F. graminearum, generated using a restriction
      enzyme-mediated integration method, identified a mutant designated R7048 showing
      pleiotropic phenotypes in several mycological traits. The vector insertion site
      in the R7048 genome was identified as the KpnI site within an ORF annotated as
      FGSG_06346 (designated FgVPS74), which showed similarity to vacuolar protein
      sorting-associated protein 74 in the baker yeast. Both targeted gene deletion and
      complementation analyses confirmed that FgVPS74 was involved in hyphal growth,
      conidiation, sexual development, mycotoxin production, and virulence towards host
      plants in F. graminearum. Electron microscopy analysis revealed no significant
      changes in morphology of the vacuole or other organelles, but a greater number of
      mitochondria were produced in the DeltaFgVPS74 strain compared to the wild-type
      progenitor. Expression of a GFP-tagged FgVPS74 construct under its native
      promoter in the DeltaFgVPS74 strain exhibited localization of GFP signal to
      putative vesicle structures, but not to the vacuolar membrane. Taken together,
      these findings demonstrated that a functional vacuolar protein-sorting pathway
      mediated by FgVPS74 is crucial for fungal growth and development in F.
      graminearum. 

PMID- 25845537
TI  - New record and enzyme activity of four species in Penicillium section Citrina
      from marine environments in Korea.
AB  - Several strains of Penicillium section Citrina were isolated during a survey of
      fungi from marine environments along the southern coast of Korea. Based on
      multigene phylogenetic analyses (beta-tubulin and calmodulin) and morphological
      characteristics, the 11 strains were identified as P. citrinum, P.
      hetheringtonii, P. paxilli, P. sumatrense, P. terrigenum, and P. westlingii. To
      understand the ecological role of these species, we tested all strains for
      extracellular enzyme activity; six strains representing four species showed beta
      glucosidase activity. Four of the identified species - P. hetheringtonii, P.
      paxilli, P. terrigenum, and P. westlingii - are new records for Korea. For these
      new species records, we describe morphological characteristics of the strains and
      compare results to published data of type strains. 

PMID- 25845539
TI  - Effect of promoter-upstream sequence on sigma38-dependent stationary phase gene
      transcription.
AB  - sigma38 in Escherichia coli is required for expression of a subset of stationary
      phase genes. However, the promoter elements for sigma38-dependent genes are
      virtually indistinguishable from that for sigma70-dependent house-keeping genes.
      hdeABp is a sigma38-dependent promoter and LEE5p is a sigma70-dependent promoter,
      but both are repressed by H-NS, a bacterial histone-like protein, which acts at
      promoter upstream sequence. We swapped the promoter upstream sequences of the two
      promoters and found that the sigma dependency was switched. This was further
      verified using lacUV5 core promoter. The results suggested that the determinant
      for sigma38-dependent promoter lies in the promoter upstream sequence. 

PMID- 25845540
TI  - Statistical experimental design optimization of rhamsan gum production by
      Sphingomonas sp. CGMCC 6833.
AB  - Rhamsan gum is a type of water-soluble exopolysaccharide produced by species of
      Sphingomonas bacteria. The optimal fermentation medium for rhamsan gum production
      by Sphingomonas sp. CGMCC 6833 was explored definition. Single-factor experiments
      indicate that glucose, soybean meal, K(2)HPO(4) and MnSO(4) compose the optimal
      medium along with and initial pH 7.5. To discover ideal cultural conditions for
      rhamsan gum production in a shake flask culture, response surface methodology was
      employed, from which the following optimal ratio was derived: 5.38 g/L soybean
      meal, 5.71 g/L K(2)HPO(4) and 0.32 g/L MnSO(4). Under ideal fermentation rhamsan
      gum yield reached 19.58 g/L +/- 1.23 g/L, 42.09% higher than that of the initial
      medium (13.78 g/L +/- 1.38 g/L). Optimizing the fermentation medium results in
      enhanced rhamsan gum production.

PMID- 25845542
TI  - DNA in the Criminal Justice System: The DNA Success Story in Perspective.
AB  - Current figures on the efficiency of DNA as an investigative tool in criminal
      investigations only tell part of the story. To get the DNA success story in the
      right perspective, we examined all forensic reports from serious (N = 116) and
      high-volume crime cases (N = 2791) over the year 2011 from one police region in
      the Netherlands. These data show that 38% of analyzed serious crime traces (N =
      384) and 17% of analyzed high-volume crime traces (N = 386) did not result in a
      DNA profile. Turnaround times (from crime scene to DNA report) were 66 days for
      traces from serious crimes and 44 days for traces from high-volume crimes.
      Suspects were truly identified through a match with the Offender DNA database of
      the Netherlands in 3% of the serious crime cases and in 1% of the high-volume
      crime cases. These data are important for both the forensic laboratory and the
      professionals in the criminal justice system to further optimize forensic DNA
      testing as an investigative tool. 

PMID- 25845541
TI  - Directed analysis of cyanobacterial membrane phosphoproteome using stained
      phosphoproteins and titanium-enriched phosphopeptides.
AB  - Gel-free shotgun phosphoproteomics of unicellular cyanobacterium Synechocystis
      sp. PCC 6803 has not been reported up to now. The purpose of this study is to
      develop directed membrane phosphoproteomic method in Synechocystis sp. Total
      Synechocystis membrane proteins were separated by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis and phosphoprotein-stained gel bands were
      selectively subjected to in-gel trypsin digestion. The phosphorylation sites of
      the resulting peptides were determined by assigning the neutral loss of [M
      H(3)PO(4)] to Ser, Thr, and Tyr residues using nano-liquid chromatography 7 Tesla
      Fourier transform mass spectrometry. As an initial application, 111 proteins and
      33 phosphoproteins were identified containing 11 integral membrane proteins.
      Identified four unknown phosphoproteins with transmembrane helices were suggested
      to be involved in membrane migration or transporters based on BLASTP search
      annotations. The overall distribution of hydrophobic amino acids in pTyr was
      lower in frequency than that of pSer or pThr. Positively charged amino acids were
      abundantly revealed in the surrounding amino acids centered on pTyr. A directed
      shotgun membrane phosphoproteomic strategy provided insight into understanding
      the fundamental regulatory processes underlying Ser, Thr, and Tyr phosphorylation
      in multi-layered membranous cyanobacteria.

PMID- 25845543
TI  - Serum osteopontin levels are upregulated and predict disability after an
      ischaemic stroke.
AB  - BACKGROUND: After an acute ischaemic stroke (AIS), several inflammatory
      biomarkers have been investigated, but their predictive role on functional
      recovery remains to be validated. Here, we investigated the prognostic relevance
      of biomarkers related to atherosclerotic plaque calcification, such as
      osteopontin (OPN), osteoprotegerin (OPG) and the receptor activator of nuclear
      factor kappa-B ligand (RANKL) in a cohort of patients with AIS (n = 90) during 90
      day follow-up. MATERIALS AND METHODS: Radiological and clinical examinations as
      well as blood sampling were performed at admission and at days 1, 7 and 90 from
      the event. Validated scores [such as modified Rankin scale (mRS) and the National
      Institutes of Health Stroke Scale (NIHSS)] were used to assess poststroke
      outcome. Serum levels of OPN, OPG and RANKL were measured by colorimetric enzyme
      linked immunosorbent assay (ELISA). RESULTS: When compared to the admission, OPN
      serum levels increased at day 7. Serum OPN levels at this time point were
      positively correlated with both ischaemic lesion volume and NIHSS at days 7 and
      90. A cut-off of 30.53 ng/mL was identified for serum OPN by receiver operating
      characteristic (ROC) curve analysis. Adjusted logistic regression showed that
      serum OPN levels at day 7 predicted worse mRS at day 90 [OR 4.13 (95% CI 1.64
      10.36); P = 0.002] and NIHSS [1.49 (95% CI 1.16-1.99); P = 0.007], independently
      of age, gender, hypertension and thrombolysis. CONCLUSIONS: Serum levels of OPN,
      but not OPG and RANKL, peaked at day 7 after AIS and predicted worse neurological
      scores. Therefore, OPN might have a pathophysiological and clinical relevance
      after AIS.

PMID- 25845544
TI  - An open multicenter comparative randomized clinical study on chitosan.
AB  - Chitosan, a natural polysaccharide derivate from chitin, offers a promising
      alternative biomaterial for use in wound dressings. In this work, the safety and
      efficacy of a next-generation KA01 chitosan wound dressing in facilitating the
      healing of nonhealing chronic wounds was studied. This open multicenter
      comparative prospective randomized clinical study was conducted at three medical
      centers in China. A total of 90 patients (45 in test group and 45 in control
      group) with unhealed chronic wounds including pressure ulcers, vascular ulcers,
      diabetic foot ulcers, and wounds with minor infections, or at risk of infection,
      were treated with the next generation chitosan wound dressing as the test article
      or traditional vaseline gauze as a control. Baseline assessments were undertaken
      with the primary end point being wound area reduction. The secondary end points
      included pain reduction (using the NRS11 pain scale) at dressing change, wound
      exudate levels, wound depth and duration of the treatment. After 4 weeks
      treatment, the wound area reduction was significantly greater in the test group
      (65.97 +/- 4.48%) than the control group (39.95 +/- 4.48%). The average pain
      level in the test group was 1.12 +/- 0.23 and 2.30 +/- 0.23 in the control group.
      The wound depth was also lower in the test group 0.30 +/- 0.48 cm than the
      control group 0.54 +/- 0.86 cm. The level of exudate fell and the dressing could
      be removed integrally in both the test and control groups. The mean duration of
      the test group was 27.31 +/- 5.37 days and control group 27.09 +/- 6.44 days. No
      adverse events were reported in either group. In conclusion this open multicenter
      comparative prospective randomized clinical study has provided compelling
      evidence that the next generation chitosan wound dressing can enhance wound
      progression towards healing by facilitating wound reepithelialization and
      reducing the patients pain level. Furthermore the dressing was shown to be
      clinically safe and effective in the management of chronic wounds.

PMID- 25845545
TI  - High Tumor Penetration of Paclitaxel Loaded pH Sensitive Cleavable Liposomes by
      Depletion of Tumor Collagen I in Breast Cancer.
AB  - The network of collagen I in tumors could prevent the penetration of drugs loaded
      in nanoparticles, and this would lead to impaired antitumor efficacy. In this
      study, free losartan (an angiotensin inhibitor) was injected before treatment to
      reduce the level of collagen I, which could facilitate the penetration of
      nanoparticles. Then the pH-sensitive cleavable liposomes (Cl-Lip) were injected
      subsequently to exert the antitumor effect. The Cl-Lip was constituted by PEG(5K)
      Hydrazone-PE and DSPE-PEG(2K)-R8. When the Cl-Lip reached to the tumor site by
      the enhanced permeability and retention (EPR) effect, PEG(5K)-Hydrazone-PE was
      hydrolyzed from the Cl-Lip under the low extra-cellular pH conditions of tumors,
      then the R8 peptide was exposed, and finally liposomes could be internalized into
      tumor cells by the mediation of R8 peptide. In vitro experiments showed both the
      cellular uptake of Cl-Lip by 4T1 cells and cytotoxicity of paclitaxel loaded Cl
      Lip (PTX-Cl-Lip) were pH sensitive. In vivo experiments showed the Cl-Lip had a
      good tumor targeting ability. After depletion of collagen I, Cl-Lip could
      penetrate into the deep place of tumors, the tumor accumulation of Cl-Lip was
      further increased by 22.0%, and the oxygen distributed in tumor tissues was also
      enhanced. The antitumor study indicated free losartan in combination with PTX-Cl
      Lip (59.8%) was more effective than injection with PTX-Cl-Lip only (37.8%) in 4T1
      tumor bearing mice. All results suggested that depletion of collagen I by
      losartan dramatically increased the penetration of PTX-Cl-Lip and combination of
      free losartan and PTX-CL-Lip could lead to better antitumor efficacy of chemical
      drugs. Thus, the combination strategy might be a promising tactic for better
      treatment of solid tumors with a high level of collagen I.

PMID- 25845546
TI  - Mirror aneurysms of the proximal segment of the anterior cerebral artery.

PMID- 25845547
TI  - Preemptive scalp infiltration with 0.5% ropivacaine and 1% lidocaine reduces
      postoperative pain after craniotomy.
AB  - BACKGROUND: In order to reduce the consequences of narcotic-related side effects
      and provide effective analgesia after craniotomy, we conducted a randomized trial
      to compare the analgesic efficacy of preemptive scalp infiltrations with 1%
      lidocaine and 0.5% ropivacaine on the postoperative pain. METHODS: Sixty adult
      patients scheduled for craniotomy were enrolled. A solution contained 0.5%
      ropivacaine and 1% lidocaine (40 ml) was prepared. In group A, local anesthetic
      was injected throughout the entire thickness of the scalp before skin incision.
      In group B, it was injected before skin closure. Additional intravenous injection
      and patient-controlled analgesia with morphine was used to control postoperative
      pain if the verbal numerical rating scale > 4. Cumulative morphine consumption;
      numerical rating scale of pain at 1, 2, 4, 6, 8, 12, and 24 h; postoperative
      nausea, vomiting, and respiratory depression, were recorded for 24 h after the
      operation. RESULTS: Postoperative pain scores were lower in group A than in group
      B within the first 6 h after surgery. Mean time to demand for postoperative
      analgesic was statistically (p < 0.001) delayed in group A 300 (240, 360) min
      compared to group B 150 (105, 200) min. Ten patients in group A received morphine
      analgesia was half less than 21 patients in group B (p < 0.006). The median
      morphine consumption in 24 h after operation in group A 10.5 (8, 15) mg was less
      than that in group B 28 (22.5, 30.5) mg (p < 0.001). CONCLUSIONS: Preemptive
      scalp infiltration with 0.5% ropivacaine and 1% lidocaine provides effective
      postoperative analgesia after craniotomy.

PMID- 25845548
TI  - Combined endonasal and sublabial endoscopic transmaxillary approach to the
      pterygopalatine fossa and orbital apex.
AB  - BACKGROUND: The pterygopalatine fossa (PPF) and inferomedial orbital apex are
      difficult regions for open neurosurgical access. The traditional extensive
      anterior approach (transfacial or transmandibular) and lateral/posterolateral
      (transcranial) approach were used to access the PPF. The combined endonasal and
      sublabial transmaxillary approach is a less invasive access route for these
      lesions. In this study, we present the technical and clinical details of our
      experience with the combined endoscopic endonasal and transmaxillary approach.
      METHODS: A retrospective analysis of our patients operated on using a combined
      endoscopic endonasal and transmaxillary approach was done. The preoperative,
      intraoperative and postoperative images and all the clinical data were evaluated.
      The accessibility to the area and extent of surgical resection were reviewed. The
      surgery-related complications and postoperative morbidities were analyzed. The
      main items of interest were the exposure of the target area and possibility for
      safe removal. RESULTS: Five patients with pathologies located in the area of the
      PPF and orbital apex were operated on using the combined endoscopic sublabial and
      endonasal transmaxillary approach. The technique provided sufficient exposure of
      the area and allowed for safe removal of the preoperatively determined target in
      all of the patients. One patient developed dry eye and a neurotrophic corneal
      ulcer, and another patient developed temporary postoperative facial numbness. In
      the follow-up, only one patient with skull base chordoma had an asymptomatic
      tumor regrowth. The other patients had no recurrence or regrowth. CONCLUSIONS:
      The combined endoscopic sublabial and endonasal transmaxillary approach is a safe
      and effective method for resection of lesions in the PPF and inferomedial orbital
      apex.

PMID- 25845549
TI  - Tractography of Meyer's loop for temporal lobe resection-validation by prediction
      of postoperative visual field outcome????.
AB  - BACKGROUND: Postoperative visual field defects are common after temporal lobe
      resection because of injury to the most anterior part of the optic radiation,
      Meyer's loop. Diffusion tensor tractography is a promising technique for
      visualizing the optic radiation preoperatively. The aim of this study was to
      assess the anatomical accuracy of Meyer's loop, visualized by the two most common
      tractography methods-deterministic (DTG) and probabilistic tractography (PTG)-in
      patients who had undergone temporal lobe resection. METHODS: Eight patients with
      temporal lobe resection for temporal lobe pathology were included. Perimetry and
      diffusion tensor imaging were performed pre- and postoperatively. Two independent
      operators analyzed the distance between the temporal pole and Meyer's loop (TP
      ML) using DTG and PTG. Results were compared to each other, to data from
      previously published dissection studies and to postoperative perimetry results.
      For the latter, Spearman's rank correlation coefficient (r(s)) was used. RESULTS:
      Median preoperative TP-ML distances for nonoperated sides were 42 and 35 mm, as
      determined by DTG and PTG, respectively. TP-ML assessed with PTG was a closer
      match to dissection studies. Intraclass correlation coefficients were 0.4 for DTG
      and 0.7 for PTG. Difference between preoperative TP-ML (by DTG and PTG,
      respectively) and resection length could predict the degree of postoperative
      visual field defects (DTG: r(s) = -0.86, p < 0.05; PTG: r(s) = -0.76, p < 0.05).
      CONCLUSION: Both DTG and PTG could predict the degree of visual field defects.
      However, PTG was superior to DTG in terms of reproducibility and anatomical
      accuracy. PTG is thus a strong candidate for presurgical planning of temporal
      lobe resection that aims to minimize injury to Meyer's loop.

PMID- 25845550
TI  - Incidence of local in-brain progression after supramarginal resection of cerebral
      metastases.
AB  - BACKGROUND: Microsurgical circumferential stripping of intracerebral metastases
      is often insufficient in achieving local tumor control. Supramarginal resection
      may improve local tumor control. METHODS: A retrospective analysis was performed
      for patients who underwent supramarginal resection of a cerebral metastasis by
      awake surgery with intraoperative cortical and subcortical stimulation, MEPs, and
      SSEPs. Supramarginal resection was achieved by circumferential stripping of the
      metastasis and additional removal of approximately 3 mm of the surrounding
      tissue. Pre- and postsurgical neurological status was assessed by the NIH Stroke
      Scale. Permanent deficits were defined by persistence after 3-month observation
      time. RESULTS: Supramarginal resection of cerebral metastases in eloquent brain
      areas was performed in 34 patients with a mean age of 60 years (range, 33-83
      years). Five out of 34 patients (14.7%) had a new transient postoperative
      neurological deficit, which improved within a few days due to supplementary motor
      area (SMA) syndrome. Five out of 34 patients (14.7%) developed a local in-brain
      progression and nine patients (26.4%) a distant in-brain progression.
      CONCLUSIONS: Supramarginal resection of cerebral metastases in eloquent locations
      is feasible and safe. Safety might be increased by intraoperative
      neuromonitoring. The better outcome in the present series may be entirely based
      on other predictors than extend of surgical resection and not necessarily on the
      surgical technique applied. However, supramarginal resection was safe and
      apparently did not lead to worse results than regular surgical techniques.
      Prospective, controlled, and randomized studies are mandatory to determine the
      possible benefit of supramarginal resection on local tumor control and overall
      outcome.

PMID- 25845551
TI  - Linear array ultrasound: a dedicated tool for a dedicated application.

PMID- 25845552
TI  - Results of re-exploration because of compromised distal blood flow after clipping
      unruptured intracranial aneurysms.
AB  - BACKGROUND: One of the major causes for performing unplanned re-exploration of a
      craniotomy after microsurgery for unruptured intracranial aneurysms (UIAs) is
      compromised distal blood flow after clipping. Therefore, it is important to
      identify the causes of compromised distal blood flow after clipping and the
      factors that influence the prognosis for re-exploration in order to decrease
      ischemic complications related to clipping UIAs. METHOD: Between January 2007 and
      December 2013, 1954 patients underwent microsurgery for UIAs. In this cohort, 20
      patients (1.0%) required unplanned re-exploration of the craniotomy for several
      reasons, and 11 patients (0.6%) underwent unplanned re-exploration with clip
      repositioning or changing of the previous clip because of compromised distal
      blood flow after clipping. Patient characteristics, aneurysm properties,
      intraoperative findings, annual incidence and prognosis were analyzed in these 11
      patients. RESULTS: The annual incidence of re-exploration has gradually decreased
      since the introduction of several intraoperative monitoring techniques. In total,
      3.0% of UIAs in the M1 trunk, 0.8% of UIAs at the origin of the anterior
      choroidal artery (AchA) and 0.5% of UIAs at the bifurcation of the middle
      cerebral artery (MCA) required re-exploration. Here, all 11 UIAs had broad necks,
      and atherosclerosis was identified around 10 UIAs. Six patients with compromised
      MCA flow demonstrated relatively better outcomes following re-exploration than
      five patients with a compromised lenticulostriate artery (LSA) or AchA flow. Four
      patients with delayed ischemic symptoms demonstrated relatively better outcomes
      than the seven patients who developed ischemic symptoms immediately
      postoperatively. CONCLUSION: Clinicians need to be more careful not to compromise
      distal blood flow when clipping UIAs at the MCA and AchA origin. Various
      intraoperative monitoring techniques can help reduce the incidence of compromised
      distal blood flow after clipping.

PMID- 25845553
TI  - Total removal of a trigeminal schwannoma via the expanded endoscopic endonasal
      approach. Technical note.
AB  - BACKGROUND: Because of their deep location surrounded by closed numerous
      neurovascular structures, skull base tumors of the cavernous sinus are still
      difficult to manage. Recently, the endoscopic endonasal approach commonly used
      for pituitary tumor resection has been "expanded" to the parasellar,
      infratemporal and orbital compartments with some advantages compared to the
      intracranial route. METHODS: The authors reported the case of a 49-year-old male
      presenting a large extradural tumor of the left cavernous sinus with extensions
      toward the orbit, sphenoid sinus and infratemporal fossa. His ophthalmological
      examination was normal, and the body CT scan revealed no primary neoplasm.
      RESULTS: In this operative video, the approach is described step by step with
      surgical nuances. The endoscopy provided a close-up panoramic view and various
      angles of vision. Also, it avoided an invasive craniotomy, cerebral retraction
      and cranial nerves damages. Thus, it allowed the total removal of this tumor
      originating from the maxillary branch of the trigeminal nerve. The pathologic
      examination confirmed a schwannoma. CONCLUSION: The expanded endoscopic endonasal
      approach provides an interesting corridor to cavernous sinus tumors with
      satisfactory control of extensions inferiorly toward the infratemporal fossa,
      anteriorly via the superior orbital fissure and medially within the sphenoid.
      Finally, the skull base surgeon has to master this anterior endoscopic route as
      well as all the other "open" transcranial skull base approaches to propose the
      best surgical route fitting the tumor characteristics.

PMID- 25845554
TI  - Superior lithium storage performance using sequentially stacked MnO2/reduced
      graphene oxide composite electrodes.
AB  - Hybrid nanostructures based on graphene and metal oxides hold great potential for
      use in high-performance electrode materials for next-generation lithium-ion
      batteries. Herein, a new strategy to fabricate sequentially stacked alpha-MnO2
      /reduced graphene oxide composites driven by surface-charge-induced mutual
      electrostatic interactions is proposed. The resultant composite anode exhibits an
      excellent reversible charge/discharge capacity as high as 1100 mA h g(-1) without
      any traceable capacity fading, even after 100 cycles, which leads to a high rate
      capability electrode performance for lithium ion batteries. Thus, the proposed
      synthetic procedures guarantee a synergistic effect of multidimensional nanoscale
      media between one (metal oxide nanowire) and two dimensions (graphene sheet) for
      superior energy-storage electrodes. 

PMID- 25845555
TI  - Allergy-test-driven elimination diet is useful in children with eosinophilic
      esophagitis, regardless of the severity of symptoms.
AB  - BACKGROUND: A combination of PPIs and corticosteroids is the pharmacotherapy
      mostly used to treat eosinophilic esophagitis (EoE), while dietetic manipulations
      consist also an efficient option. The aim of this study was to compare the
      efficacy of allergy-test-driven elimination diet in children with mild symptoms
      of EoE to a group of children with moderate/severe symptoms. METHODS: Thirty-five
      children, aged 7 months to 12 yr, with EoE were enrolled in the study. They had a
      clinical history of GERD-like (21 children, Group A) or more severe symptoms (14
      children, Group B). The diagnosis had been confirmed after two preliminary months
      of therapy with PPIs and an esophagogastroduodenoscopy. Soon after diagnosis,
      they were allergy-tested, using IgE detection (SPT and serum-specific IgE) and
      atopy patch tests (APTs). A 12-month tailor-made diet was prescribed according to
      the tests. Patients of Group B continued PPIs for two more months, while
      swallowed topical steroids were also prescribed to them for the first 5 months
      after diagnosis, followed by an 'as-needed' use of them for the rest of the
      study. Endoscopy was repeated at the end of the study. RESULTS: Milk and egg were
      the most common APT-positive allergens. Thirty-two patients were instructed to
      follow an elimination diet, which was completed by 15/18 of Group A and 12/14 of
      Group B. An improvement of symptoms was reported by 26/27 patients that completed
      the study. The use of swallowed corticosteroids was noticeably decreased during
      the as-needed period, in Group B. A remarkable reduce of eosinophils was noticed
      in biopsies; from 42.84 +/- 18.08, they decreased to 6.41 +/- 3.20, a year after.
      CONCLUSION: All children with EoE and mild symptoms had resolution of symptoms
      and normal eosinophils in the esophageal mucosa a year after an allergy-driven
      elimination diet. Patients with moderate/severe EoE symptoms had the same
      improvement, indicating that an elimination diet is an efficient complementary
      treatment to corticosteroids.

PMID- 25845557
TI  - Highly enantioselective transfer hydrogenation of ketones with chiral (NH)2 P2
      macrocyclic iron(II) complexes.
AB  - Bis(isonitrile) iron(II) complexes bearing a C2 -symmetric diamino (NH)2 P2
      macrocyclic ligand efficiently catalyze the hydrogenation of polar bonds of a
      broad scope of substrates (ketones, enones, and imines) in high yield (up to 99.5
      %), excellent enantioselectivity (up to 99 % ee), and with low catalyst loading
      (generally 0.1 mol %). The catalyst can be easily tuned by modifying the
      substituents of the isonitrile ligand. 

PMID- 25845556
TI  - Tetraarsenic hexoxide demonstrates anticancer activity at least in part through
      suppression of NF-kappaB activity in SW620 human colon cancer cells.
AB  - Tetraarsenic hexoxide (As4O6) has been used in Korean traditional medicine for
      the treatment of cancer since the late 1980's, and arsenic trioxide (As2O3) is
      currently used as a chemotherapeutic agent. Previous studies suggest that the
      As4O6-induced cell death pathway is different from that of As2O3 and its
      mechanism of anticancer activity remains unclear. Nuclear factor (NF)-kappaB is a
      well-known transcription factor involved in cell proliferation, invasion and
      metastasis. Hence, in the present study, we investigated the effects of As4O6 on
      NF-kappaB activity and NF-kappaB-regulated gene expression in vitro and in vivo.
      The cytotoxicity assay revealed that As4O6 inhibited the growth of SW620 cells in
      a dose-dependent manner, and the half maximal inhibitory concentration (IC50) was
      ~1 uM after a 48 h treatment. As4O6 suppressed NF-kappaB activation and
      suppressed inhibitory kappaBalpha (IkappaBalpha) phosphorylation stimulated by
      tumor necrosis factor (TNF). As4O6 also suppressed downstream NF-kappaB-regulated
      proteins involved in cancer anti-apoptosis, proliferation, invasion and
      metastasis. In addition, As4O6 marginally suppressed tumor growth and the anti-NF
      kappaB activity was confirmed using an in vivo xenograft mouse model in which
      animals were injected with SW620 cells. The present study provides evidence that
      As4O6 has anticancer properties through suppression of NF-kappaB activity and NF
      kappaB-mediated cellular responses.

PMID- 25845558
TI  - Isolation and purification of monosialotetrahexosylgangliosides from pig brain by
      extraction and liquid chromatography.
AB  - Monosialotetrahexosylganglioside (GM1), one of glycosphingolipids containing
      sialic acid, plays particularly important role in fighting against paralysis,
      dementia and other diseases caused by brain and nerve damage. In this work, a
      simple and highly efficient method with high yield was developed for isolation
      and purification of GM1 from pig brain. The method consisted of an extraction by
      chloroform-methanol-water and a two-step chromatographic separation by DEAE
      Sepharose Fast Flow anion-exchange medium and Sephacryl S-100 HR size-exclusion
      medium. The purified GM1 was proved to be homogeneous and had a purity of >98.0%
      by high-performance anion-exchange and size-exclusion chromatography. The
      molecular weight was 30.0 kDa by high-performance size-exclusion chromatography
      and 1546.9 Da by electrospray ionization mass spectrometry. The chromogenic
      reaction by resorcinol-hydrochloric acid solution indicated that the purified GM1
      showed a specific chromogenic reaction of sialic acid. Through this isolation and
      purification program, ~1.0 mg of pure GM1 could be captured from 500 g wet pig
      brain tissue and the yield of GM1 was around 0.022%, which was higher than the
      yields by other methods. The method may provide an alternative for isolation and
      purification of GM1 in other biological tissues.

PMID- 25845559
TI  - The WNT system: background and its role in bone.
AB  - WNTs are extracellular proteins that activate different cell surface receptors
      linked to canonical and noncanonical WNT signalling pathways. The Wnt genes were
      originally discovered as important for embryonic development of fruit flies and
      malignant transformation of mouse mammary cancers. More recently, WNTs have been
      implicated in a wide spectrum of biological phenomena and diseases. During the
      last decade, several lines of clinical and preclinical evidence have indicated
      that WNT signalling is critical for trabecular and cortical bone mass, and this
      pathway is currently an attractive target for drug development. Based on detailed
      knowledge of the different WNT signalling pathways, it appears that it might be
      possible to develop drugs that specifically target cortical and trabecular bone.
      Neutralization of a bone-specific WNT inhibitor is now being evaluated as a
      promising anabolic treatment for patients with osteoporosis. Here, we provide the
      historical background to the discoveries of WNTs, describe the different WNT
      signalling pathways and summarize the current understanding of how these proteins
      regulate bone mass by affecting bone formation and resorption. 

PMID- 25845560
TI  - Response to: 'Standard excision and reconstruction as an alternative to MMS for
      giant basal cell carcinoma? - Commentary'.

PMID- 25845561
TI  - Screening of cannabinoids in industrial-grade hemp using two-dimensional liquid
      chromatography coupled with acidic potassium permanganate chemiluminescence
      detection.
AB  - Widely known for its recreational use, the cannabis plant also has the potential
      to act as an antibacterial agent in the medicinal field. The analysis of cannabis
      plants/products in both pharmacological and forensic studies often requires the
      separation of compounds of interest and/or accurate identification of the whole
      cannabinoid profile. In order to provide a complete separation and detection of
      cannabinoids, a new two-dimensional liquid chromatography method has been
      developed using acidic potassium permanganate chemiluminescence detection, which
      has been shown to be selective for cannabinoids. This was carried out using a
      Luna 100 A CN column and a Poroshell 120 EC-C18 column in the first and second
      dimensions, respectively. The method has utilized a large amount of the available
      separation space with a spreading angle of 48.4 degrees  and a correlation of
      0.66 allowing the determination of more than 120 constituents and mass spectral
      identification of ten cannabinoids in a single analytical run. The method has the
      potential to improve research involved in the characterization of sensitive,
      complex matrices. 

PMID- 25845562
TI  - Toll-like receptors.
AB  - The mammalian Toll-like receptor (TLR) family consists of 13 members, and
      recognizes specific patterns of microbial components, called pathogen-associated
      molecular patterns (PAMPs). TLR-dependent recognition of PAMPs leads to
      activation of the innate immune system, which subsequently leads to activation of
      antigen-specific adaptive immunity. The TLR-mediated signaling pathways consist
      of the MyD88-dependent pathway and TRIF-dependent pathway, both of which induce
      gene expression. This unit discusses mammalian TLRs (TLR1 to 13) that have an
      essential role in the innate immune recognition of microorganisms. Also discussed
      are TLR-mediated signaling pathways and antibodies that are available to detect
      specific TLRs.

PMID- 25845563
TI  - Measurement of bacterial ingestion and killing by macrophages.
AB  - This unit presents assays that allow accurate measurement of phagocytosis and
      killing of bacteria by macrophages. The first basic protocol describes how to
      measure the ability of macrophages to ingest bacteria. Importantly, because
      macrophage phagocytosis entails separate binding and internalization steps,
      assays are described here that will also determine the extent to which bacteria
      bound to the macrophage are in fact internalized. Two effective methods to do
      this are described in alternate protocols. Both of these alternate protocols rely
      on enumeration of differentially labeled bacteria by fluorescence microscopy to
      distinguish intracellular from extracellular bacteria. The unit also presents two
      protocols to measure the ability of a macrophage to kill bacteria it has
      internalized. The second basic is a straightforward assay in which bacterial
      colonies are enumerated before and after a killing period. Bactericidal activity
      is evidenced by reduced CFU bacteria on agar plates. Because it is critical to
      remove residual extracellular organisms, the protocol presents two alternative
      steps to accomplish this: a washing procedure and a more stringent method in
      which cells are sedimented through sucrose. An alternate protocol describes a way
      to measure bacterial viability based on bacterial metabolism, in which the
      ability of bacterial dehydrogenases to mediate the reduction of a tetrazolium
      salt to purple formazan is monitored by measuring absorbance
      spectrophotometrically.

PMID- 25845564
TI  - Heymann nephritis in Lewis rats.
AB  - Human membranous nephritis is a major cause of end-stage kidney disease. Active
      Heymann nephritis (HN) is an auto-immune model of membranous nephritis induced in
      Lewis rats by immunization with a crude renal tubular antigen (Fx1A) or megalin
      (gp330). The pathogenesis of HN is through the binding of anti-Fx1A
      autoantibodies to the auto-antigen expressed on glomerular epithelial cells,
      resulting in severe glomerular injury and proteinuria. The pathological features
      of HN include immune deposits in glomeruli and infiltration of glomeruli and the
      tubulointerstitium by macrophages and T cells. This unit describes the method of
      the preparation of Fx1A and the induction of HN in Lewis rats by immunization
      with Fx1A.

PMID- 25845565
TI  - Use of proteasome inhibitors.
AB  - Proteasome inhibitors are indispensable research tools in immunology and cell
      biology. With numerous proteasome inhibitors available commercially, choosing the
      appropriate compound for a biological experiment may be challenging, especially
      for a novice. This unit provides an overview of the proteasome inhibitors
      commonly used in research. It discusses how to select an appropriate highly
      specific inhibitor, its concentration, and length of exposure for mammalian cell
      culture experiments. In addition, assays that can be used to confirm proteasome
      inhibition are discussed.

PMID- 25845567
TI  - Quantifying the severity of hurricanes on extinction probabilities of a primate
      population: Insights into "Island" extirpations.
AB  - Long-term studies quantifying impacts of hurricane activity on growth and
      trajectory of primate populations are rare. Using a 14-year monitored population
      of Alouatta palliata mexicana as a study system, we developed a modeling
      framework to assess the relative contribution of hurricane disturbance and two
      types of human impacts, habitat loss, and hunting, on quasi-extinction risk. We
      found that the scenario with the highest level of disturbance generated a 21%
      increase in quasi-extinction risk by 40 years compared to scenarios of
      intermediate disturbance, and around 67% increase relative to that found in low
      disturbance scenarios. We also found that the probability of reaching quasi
      extinction due to human disturbance alone was below 1% by 40 years, although such
      scenarios reduced population size by 70%, whereas the risk of quasi-extinction
      ranged between 3% and 65% for different scenarios of hurricane severity alone, in
      absence of human impacts. Our analysis moreover found that the quasi-extinction
      risk driven by hunting and hurricane disturbance was significantly lower than the
      quasi-extinction risk posed by human-driven habitat loss and hurricane
      disturbance. These models suggest that hurricane disturbance has the potential to
      exceed the risk posed by human impacts, and, in particular, to substantially
      increase the speed of the extinction vortex driven by habitat loss relative to
      that driven by hunting. Early mitigation of habitat loss constituted the best
      method for reducing quasi-extinction risk: the earlier habitat loss is halted,
      the less vulnerable the population becomes to hurricane disturbance. By using a
      well-studied population of A. p. mexicana, we help understand the demographic
      impacts that extreme environmental disturbance can trigger on isolated
      populations of taxa already endangered in other systems where long-term
      demographic data are not available. For those experiencing heavy anthropogenic
      pressure and lacking sufficiently evolved coping strategies against unpredictable
      environmental disturbance, the risk of population extinction can be exacerbated.

PMID- 25845566
TI  - Altered relation between lipopolysaccharide-induced inflammatory response and
      excitotoxicity in rat organotypic hippocampal slice cultures during ethanol
      withdrawal.
AB  - BACKGROUND: Ethanol (EtOH) causes neurotoxicity by several mechanisms including
      excitotoxicity and neuroinflammation, but little is known about the interaction
      between these mechanisms. Because neuroinflammation is known to enhance
      excitotoxicity, we hypothesized that neuroinflammation contributes to the
      enhanced excitotoxicity, which is associated with EtOH withdrawal (EWD). The aim
      of this study was to evaluate the lipopolysaccharide (LPS)-induced inflammatory
      response of cultured hippocampal tissue during EWD and its effects on the
      enhanced N-methyl-d-aspartate (NMDA) receptor-mediated excitotoxicity, which
      occurs at this time. METHODS: Using a neonatal organotypic hippocampal slice
      culture (OHSC) model, we assessed the effects of NMDA and LPS (separately or
      combined) during EWD after 10 days of EtOH exposure. Neurotoxicity was assessed
      using propidium iodide uptake, and the inflammatory response was evaluated by
      measuring the release of tumor necrosis factor (TNF)-alpha (quantified by enzyme
      linked immunosorbent assay) and nitric oxide (NO; quantified by the Griess
      reaction) into culture media. Furthermore, we explored the potential role of the
      microglial cell type using immortalized BV2 microglia treated with EtOH for 10
      days and challenged with LPS during EWD. RESULTS: As predicted, NMDA-induced
      toxicity was potentiated by LPS under control conditions. However, during EWD,
      the reverse was observed and LPS inhibited peak NMDA-induced toxicity.
      Additionally, LPS-induced release of TNF-alpha and NO during EWD was reduced
      compared to control conditions. In BV2 microglia, following EtOH exposure, LPS
      induced release of NO was reduced, whereas TNF-alpha release was potentiated.
      CONCLUSIONS: During EWD following chronic EtOH exposure, OHSC exhibited a
      desensitized inflammatory response to LPS and the effects of LPS on NMDA toxicity
      were reversed. This might be explained by a change in microglia to an anti
      inflammatory and neuroprotective phenotype. In support, studies on BV2 microglia
      indicate that EtOH exposure and EWD do alter the response of these cells to LPS,
      but this cannot fully explain the changes observed in the OHSC. The data suggest
      that neuroinflammation and excitotoxicity do interact during EWD. However, the
      interaction is not as simple as we originally proposed. This in turn illustrates
      the need to assess the extent, importance, and relation of these mechanisms in
      models of EtOH exposure producing neurotoxicity.

PMID- 25845575
TI  - Caffeic acid, a phyto polyphenol mitigates fluoride induced hepatotoxicity in
      rats: A possible mechanism.
AB  - Fluoride induced hepatotoxicity has been extensively studied in both humans and
      animals. However, the mechanism underlying in the hepatotoxicity of experimental
      fluorosis remains obscure. The severity of fluoride toxicity was reduced by oral
      administration of certain plant derived antioxidants. Caffeic acid (CA) a
      polyphenolic compound has diverse range of pharmacological activity in the
      biological system. Therefore, the present study was aimed to investigate the
      protective mechanism of CA, against fluoride induced hepatotoxicity in rats. The
      rats were treated with 300 ppm of NaF via drinking water ad libitum alone and in
      combination with CA at a dose of 50 mg/kg daily for 30 days by oral intubation.
      CA treatment significantly prevented fluoride induced hepatic damage as evident
      from the histopathological studies and declined levels of serum fluoride and
      liver marker enzymes. A significant decrease in the levels of enzymatic (SOD2,
      CAT, GPx, and GSTpi class) and nonenzymatic (GSH and Vitamin C) antioxidants
      along with increased ROS, lipid peroxidation, protein carbonyl content, and
      nitrate levels by fluoride were also prevented in these groups. In addition, CA
      inhibits fluoride induced apoptosis by altering the Bax and caspase-3p20
      expressions. Further, fluoride induced upregulation of Nox4, p38alpha MAPK,
      Hsp60, and downregulation of Hsp27 are the indicators for the detection of
      oxidative damage, apoptosis, and mitochondrial stress was also modulated by CA.
      These findings reveal that CA supplementation has a protective effect against
      fluoride induced hepatotoxicity in rats.

PMID- 25845576
TI  - Regional segmentation of ventricular models to achieve repolarization dispersion
      in cardiac electrophysiology modeling.
AB  - The electrocardiogram (ECG) is one of the most significant outputs of a
      computational model of cardiac electrophysiology because it relates the numerical
      results to clinical data and is a universal tool for diagnosing heart diseases.
      One key features of the ECG is the T-wave, which is caused by longitudinal and
      transmural heterogeneity of the action potential duration (APD). Thus, in order
      to model a correct wave of repolarization, different cell properties resulting in
      different APDs must be assigned across the ventricular wall and longitudinally
      from apex to base. To achieve this requirement, a regional parametrization of the
      heart is necessary. We propose a robust approach to obtain the transmural and
      longitudinal segmentation in a general heart geometry without relying on ad hoc
      procedures. Our approach is based on auxiliary harmonic lifting analyses, already
      used in the literature to generate myocardial fiber orientations. Specifically,
      the solution of a sequence of Laplace boundary value problems allows
      parametrically controlled segmentation of both heart ventricles. The flexibility
      and simplicity of the proposed method is demonstrated through several
      representative examples, varying the locations and extents of the epicardial,
      midwall, and endocardial layers. Effects of the control parameters on the T-wave
      morphology are illustrated via computed ECGs.

PMID- 25845577
TI  - Evolving characteristics and outcome of secondary acute promyelocytic leukemia
      (APL): A prospective analysis by the French-Belgian-Swiss APL group.
AB  - BACKGROUND: Reports of patients with secondary acute promyelocytic leukemia (APL)
      have increased in recent years, particularly for those who received treatment
      with mitoxantrone, and retrospective studies have suggested that their
      characteristics and outcomes were similar to those of patients with de novo APL.
      METHODS: The authors investigated patients with de novo and secondary APL who
      were included in the ongoing APL-2006 trial. Patients with secondary APL who were
      included in that trial also were compared with a previous retrospective cohort of
      patients with secondary APL. RESULTS: In the APL-2006 trial, 42 of 280 patients
      (15%) had secondary APL. Compared with the retrospective cohort, patients with
      secondary APL in the APL-2006 trial had a lower incidence of prior breast
      carcinoma (35.7% vs 57%; P = .03) and a higher incidence of prior prostate
      carcinoma (26.2% vs 4.7%; P < .001). Treatment of the primary tumor in the APL
      2006 trial less frequently included combined radiochemotherapy (28.6% vs 47.2%; P
      = .044) and no mitoxantrone (0% vs 46.7%; P = .016) but more frequently included
      anthracyclines (53.3% vs 38.3%; P = .015). In the APL-2006 trial, patients who
      had secondary APL, compared with those who had de novo APL, were older (mean,
      60.2 years vs 48.7 years, respectively; P < .0001) but had a similar complete
      response rate (97.6% vs 90.3%, respectively), cumulative incidence of relapse (0%
      vs 1.8%, respectively), and overall survival (92.3% vs 90.9%, respectively) at 18
      months. CONCLUSIONS: Although the incidence of secondary APL appears to be stable
      over time, evolving strategies for the treatment of primary cancers have reduced
      its occurrence among breast cancer patients but have increased its incidence
      among patients with prostate cancer. The current results confirm prospectively
      that patients with secondary APL have characteristics and outcomes similar to
      those of patients with de novo APL.

PMID- 25845578
TI  - Pulmonary nodules in liver transplant candidates with hepatocellular carcinoma:
      Imaging characteristics and clinical outcomes.
AB  - No guidelines exist for the management of pulmonary nodules in patients with
      hepatocellular carcinoma (HCC) who are being evaluated for liver transplantation.
      The 172 patients with HCC who were listed for liver transplant at our institution
      received both pretransplant chest computed tomography (CT) and follow-up CT.
      Pulmonary nodules on CT were characterized and followed on subsequent scans by a
      blinded radiologist, with a consensus review with a second radiologist being
      performed for equivocal cases. Nodule characteristics and outcomes were examined
      with chi-square tests, and the posttransplant survival of patients with different
      nodule outcomes was compared. Cumulative probabilities of waiting-list removal
      for nontransplant patients and cumulative probabilities of undergoing
      transplantation for all patients were also compared between patients with and
      without pulmonary nodules. Of all the patients, 76.2% had at least 1 pulmonary
      nodule on pretransplant CT, with 301 total nodules characterized; 2.7% of nodules
      represented HCC metastases, 1.0% represented other bronchopulmonary malignancies,
      and 2.7% represented infections. None of the malignant nodules exhibited a
      triangular/lentiform shape or calcifications. There were no statistically
      significant differences in pulmonary nodule outcomes between patients who
      underwent transplantation and those who did not undergo transplantation. No
      significant differences in posttransplant survival were found between patients
      with different nodule outcomes. There was also no significant difference between
      patients with and without nodules in the cumulative probabilities of waiting-list
      removal. However, the cumulative probability of undergoing liver transplantation
      was borderline significantly higher in patients without pulmonary nodules. In
      conclusion, despite the low prevalence of malignant nodules, all pulmonary
      nodules besides triangular/lentiform-shaped or calcified nodules should be
      followed with serial CT while the patient is on the transplant list, with biopsy
      performed for new and/or enlarged nodules. Both malignancy and active infection
      must be excluded when one is confronted with enlarged pulmonary nodules.
      Clinicians should also be aware of the possibility of reactivation of a
      granulomatous infection after transplantation.

PMID- 25845579
TI  - CLINICAL CONSEQUENCES OF THE REVISED DSM-5 DEFINITION OF AGORAPHOBIA IN TREATMENT
      SEEKING ANXIOUS YOUTH.
AB  - BACKGROUND: In DSM-5, the agoraphobia core symptom criterion has been revised to
      require fear about multiple situations from across at least two distinct domains
      in which escape might be difficult or panic-like symptoms might develop. The
      present study examined patterns and correlates of the recent change in a sample
      of anxious youth with symptom presentations consistent with the DSM-IV
      agoraphobia definition and/or specific phobia (SP) to consider how the recent
      diagnostic change impacts the prevalence and composition of agoraphobia in
      children and adolescents. METHOD: Analyses (N = 151) evaluated impairment and
      correlates of agoraphobic youth who no longer meet the DSM-5 agoraphobia criteria
      relative to agoraphobic youth who do meet the new DSM-5 criteria. Secondary
      analyses compared agoraphobic youth not meeting DSM-5 criteria to SP youth.
      RESULTS: One-quarter of youth with symptom presentations consistent with the DSM
      IV agoraphobia definition no longer met criteria for DSM-5 agoraphobia, but
      showed comparable severity and impairment across most domains to youth who do
      meet criteria for DSM-5 agoraphobia. Further, these youth showed higher levels of
      anxiety sensitivity and internalizing psychopathology relative to youth with SP.
      CONCLUSIONS: A substantial proportion of impaired youth with considerable
      agoraphobic symptom presentations have been left without a specified anxiety
      diagnosis by the DSM-5, which may affect their ability to receive and/or get
      coverage for services and their representation in treatment evaluations. Future
      DSM iterations may do well to include a "circumscribed" agoraphobia specifier
      that would characterize presentations of fear or anxiety about multiple
      situations, but that do not span across at least two distinct situational
      domains.

PMID- 25845580
TI  - Characterization of facial phenotypes of children with congenital hypopituitarism
      and their parents: a matched case-control study.
AB  - Congenital Hypopituitarism (CH) has traditionally been associated with specific
      facial phenotypes subsumed under the term midface retrusion, based on
      cephalometric studies. In this study, we used a systematic anthropometric
      approach to facial morphology in 37 individuals with CH and their parents,
      primarily of French Canadian ancestry, and compared them to a control group of 78
      French Canadian patients with well-controlled type 1 diabetes and their parents.
      We were able to demonstrate clear morphological differences, which were more
      prevalent in the affected group than in the control group. More specifically, we
      showed the presence of a shorter skull base width (P < 0.001) and reduced inner
      canthal distance (P = 0.006) in the CH face, as well as a relative
      underdevelopment of the mandible (P = 0.001). These findings were present in
      individuals of all ages, and were independent of the duration of growth hormone
      treatment (median treatment 90.8 months; range 7.2-175.8 months). In addition,
      skull base width was significantly reduced in both mothers and fathers of
      affected children compared to the parents of the controls (P < 0.001), despite
      comparable parental heights, supporting an underlying genetic etiology. Such
      extensive phenotypic studies have not been done in congenital hypopituitarism and
      will provide further opportunities for data mining.

PMID- 25845581
TI  - Sensitive imaging of magnetic nanoparticles for cancer detection by active
      feedback MR.
AB  - PURPOSE: Sensitive imaging of superparamagnetic nanoparticles or aggregates is of
      great importance in MR molecular imaging and medical diagnosis. For this purpose,
      a conceptually new approach, termed active feedback magnetic resonance, was
      developed. METHODS: In the presence of the Zeeman field, a dipolar field is
      induced by the superparamagnetic nanoparticles or aggregates. Such dipolar field
      creates spatial and temporal (due to water diffusion) variations to the
      precession frequency of the nearby water 1 H magnetization. Sensitive imaging of
      magnetic nanoparticles or aggregates can be achieved by manipulating the
      intrinsic spin dynamics by selective self-excitation and fixed-point dynamics
      under active feedback fields. RESULTS: Phantom experiments of superparamagnetic
      nanoparticles; in vitro experiments of brain tissue with blood clots; and in vivo
      mouse images of colon cancers, with and without labeling by magnetic
      nanoparticles, suggest that this new approach provides enhanced, robust, and
      positive contrast in imaging magnetic nanoparticles or aggregates for cancer
      detection. CONCLUSION: The spin dynamics originated from selective self
      excitation and fixed-point dynamics under active feedback fields have been shown
      to be sensitive to dipolar fields generated by magnetic nanoparticles. Magn Reson
      Med 74:33-41, 2015. (c) 2014 Wiley Periodicals, Inc.

PMID- 25845582
TI  - Calcium channel blocker use and risk of Parkinson's disease: a meta-analysis.
AB  - PURPOSES: Whether calcium channel blocker (CCB) use contributes to a low risk of
      developing a first time diagnosis of Parkinson's disease (PD) remains
      controversial. We conducted a meta-analysis to investigate the relationship
      between CCB use and PD risk. METHODS: Pubmed, EMBASE, China National Knowledge
      Infrastructure, and WanFang databases were searched for papers through May 2014.
      Studies investigating the association between CCB use and the risk of first time
      diagnosis of PD were included. Pooled adjusted risk ratio (RR) and 95% confidence
      interval (CI) were calculated using a fixed-effect model. RESULTS: Five studies
      involving 208 248 CCB users were identified. Overall, CCB use was associated with
      a reduction in PD risk (RR = 0.76, 95%CI = 0.68-0.84) compared with the controls.
      Subgroup analysis showed that dihydropyridine CCB use reduced by 27% PD risk (RR
      = 0.73, 95%CI = 0.64-0.83) and non-dihydropyridine CCB use reduced by 30% PD risk
      (RR = 0.70, 95%CI = 0.50-0.93). CONCLUSIONS: Overall, CCB use as a class is
      associated with a reduction in PD risk. Both of dihydropyridine and non
      dihydropyridine CCB use appear to reduce the risk of developing a first time
      diagnosis of PD. More well-designed prospective studies are needed to investigate
      the difference of the subtype of CCB user on PD risk.

PMID- 25845583
TI  - Salt stress response of membrane proteome of sugar beet monosomic addition line
      M14.
AB  - Understanding how plants respond to and tolerate salt stress is important for
      engineering and breeding effort to boost plant productivity and bioenergy in an
      ever challenging environment. Sugar beet M14 line is a unique germplasm that
      contains genetic materials from Beta vulgaris L. and Beta corolliflora Zoss, and
      it exhibits tolerance to salt stress. Here we report the changes in membrane
      proteome of the M14 plants in response to salt stress (0, 200, 400mM NaCl) using
      an iTRAQ two-dimensional LC-MS/MS technology for quantitative proteomic analysis.
      In total, 274 proteins, mostly membrane proteins, were identified, and 50
      proteins exhibited differential protein level changes, with 40 proteins increased
      and 10 decreased. The proteins were mainly involved in transport, metabolism,
      protein synthesis, photosynthesis, protein folding and degradation, signal
      transduction, stress and defense, energy, and cell structure. These results have
      revealed interesting mechanisms underlying the M14 response and tolerance to salt
      stress. BIOLOGICAL SIGNIFICANCE: Sugar beet monosomic addition line M14 is a
      special variety with salt stress tolerance. Analysis of the M14 membrane proteome
      under salt stress may provide useful information regarding specific adaptive
      mechanisms underlying salt stress tolerance. Membrane proteins are known to play
      critical roles in salt stress signaling and adaptation. The purpose of this study
      was to identify significantly changed membrane proteins and determine their
      possible relevance to salt tolerance. The proteomic analysis of the M14 line
      revealed important molecular mechanisms that can be potentially applied to
      improving crop salt tolerance. This article is part of a Special Issue entitled:
      Proteomics in India.

PMID- 25845584
TI  - Proteomic analysis of the response of Escherichia coli to short-chain fatty
      acids.
AB  - Given their simple and easy-to-manipulate chemical structures, short-chain fatty
      acids (SCFAs) are valuable feedstocks for many industrial applications. While the
      microbial production of SCFAs by engineered Escherichia coli has been
      demonstrated recently, productivity and yields are limited by their antimicrobial
      properties. In this work, we performed a comparative proteomic analysis of E.
      coli under octanoic acid stress (15 mM) and identified the underlying mechanisms
      of SCFA toxicity. Out of a total of 33 spots differentially expressed at a p
      value <= 0.05, nine differentially expressed proteins involved in transport and
      structural roles (OmpF, HPr, and FliC), oxidative stress (SodA, SodB, and TrxA),
      protein synthesis (PPiB and RpsA) and metabolic functions (HPr, PflB) were
      selected for further investigation. Our studies suggest that membrane damage and
      oxidative stress are the main routes of inhibition by SCFAs in E. coli. The outer
      membrane porin OmpF had the greatest impact on SCFA tolerance. Intracellular pH
      analysis on ompF mutants grown under octanoic acid stress indicated that this
      porin facilitates transport of SCFAs into the cell. The same response was
      observed under hexanoic acid stress, further supporting the role of OmpF in
      response to the presence of SCFAs. Furthermore, analysis of membrane protein
      expression revealed that other outer membrane porins are also involved in the
      response of E. coli to SCFAs. BIOLOGICAL SIGNIFICANCE: This work covers the first
      known proteomic analysis to assess the inhibitory effect of SCFAs in E. coli.
      SCFAs are molecules of great interest in the industry, but their microbial
      production is limited by their antimicrobial properties. This work allowed
      identification of differentially expressed proteins in response to SCFA stress
      and demonstrated the relevance of short- and medium-chain FA transport across the
      cell membrane via outer membrane porins, providing valuable insights on the
      toxicity mechanism of SCFAs in E. coli. These results could also benefit future
      engineering efforts by guiding the design and construction of industrial strains
      that produce SCFAs with increased tolerance and productivity.

PMID- 25845585
TI  - New insights into the human brain proteome: Protein expression profiling of deep
      brain stimulation target areas.
AB  - Deep brain stimulation (DBS) is a neurosurgical procedure that provides
      therapeutic benefits for movement and affective disorders. The nucleus basalis of
      Meynert (NBM) and substantia nigra (SN) are considered target areas to apply DBS.
      Even though the degeneration of NBM and SN underlies the cognitive decline
      observed in neurological diseases, the protein knowledge derived from both areas
      is scarce. We have characterized the proteome present in both subcortical brain
      areas using the Triple TOF 5600 mass spectrometer, identifying 2775 and 3469
      proteoforms in NBM and SN respectively. Data mining of MS-generated proteomic
      data have revealed that: i) 675 proteins tend to localize to synaptic ending, ii)
      61% of the global dataset is also present in human CSF and/or plasma, and iii)
      894 proteins have not been previously identified in healthy brain by MS. The
      correlation of NBM and SN proteomic expression profiles with human brain
      transcriptome data available at Allen Brain Atlas has revealed protein evidence
      for 250 genes considered with brain-wide expression and 112 genes with region
      specific expression in human brain. In addition, protein datasets have been
      classified according to their chromosomal origin, increasing the current proteome
      coverage in healthy human brain. BIOLOGICAL SIGNIFICANCE: The nucleus basalis of
      Meynert and substantia nigra are brain areas of clinical interest to apply the
      deep brain stimulation (DBS) technology in neurosurgery. Our proteomic
      characterization has revealed 675 proteins involved in the regulation of synaptic
      transmission, electrical machinery, and neurotransmitter release in both DBS
      target areas. Moreover, 2599 identified proteins present capacity to be secreted
      to the CSF and plasma. Our data contribute to a further step towards the
      characterization of the anatomical atlas of the human brain proteome, detecting
      652 proteins that are common between different basal ganglia structures. This
      article is part of a Special Issue entitled: HUPO 2014.

PMID- 25845586
TI  - iTRAQ-based quantitative proteomic analysis of Pseudomonas aeruginosa SJTD-1: A
      global response to n-octadecane induced stress.
AB  - N-octadecane, the shortest solid-state alkane, was efficiently consumed by
      Pseudomonas aeruginosa SJTD-1. To reveal its mechanism, the iTRAQ-LC-MS/MS
      strategy was applied for quantification of proteins in response to alkane. As a
      result, 383 alkane-responsive proteins were identified and these proteins could
      be linked to multiple biochemical pathways. Above all, the level of alkane
      hydroxylase AlkB2 has been significantly higher in alkane condition. Also, the
      presence of a putative novel AlmA-like monooxygenase and its role on alkane
      hydroxylation were firstly proposed in Pseudomonas. In addition, other proteins
      for chemotaxic, beta-oxidation, glyoxylate bypass, alkane uptake, cross membrane
      transport, enzymatic steps and the carbon flow may have important roles in the
      cellular response to alkane. Most of those differently expressed proteins were
      functionally mapped into pathways of alkane degradation or metabolism thereof. In
      this sense, findings in this study provide critical clues to reveal
      biodegradation of long chain n-alkanes and rationally be important for potent
      biocatalyst for bioremediation in future. BIOLOGICAL SIGNIFICANCE: We use iTRAQ
      strategy firstly to compare the proteomes of Pseudomonas SJTD-1 degrading alkane.
      Changes in protein clearly provide a comprehensive overview on alkane
      hydroxylation of SJTD-1, including those proteins for chemotaxis, alkane uptake,
      cross membrane transport, enzymatic steps and the carbon flow. AlkB2 and a
      putative novel AlmA-like monooxygenase have been highlighted for their
      outstanding contribution to alkane use. We found that several chemotaxic proteins
      were altered in abundance in alkane-grown cells. These results may be helpful for
      understanding alkane use for Pseudomonas.

PMID- 25845587
TI  - Non-chemotherapy drug-induced agranulocytosis in a tertiary hospital.
AB  - Drug-induced agranulocytosis is a rare haematological disorder considered as
      severe adverse drug reaction. Due to its low incidence, the number of studies are
      low and the variability of clinical features and presentation in hospitalized
      patients is rarely described. Awe performed an observational, transversal and
      retrospective study in the haematology and toxicology unit in a tertiary hospital
      located in Spain (Valencia) (1996-2010) in order to assess its incidence, the
      drugs involved, the management and outcomes of drug-induced agranulocytosis.
      Twenty-one cases of agranulocytosis were retrieved. All of them presented severe
      and symptomatic agranulocytosis (fever and infection). The most common drug
      associated with drug-induced agranulocytosis was metamizole administration but
      other drugs belonging to different pharmacological classes as well (carbimazol,
      sulfasalazine, bisoprolol, itraconazole, amitryptiline, ketorolac and
      claritomicine+cefuroxime). No differences between sex and age were found in
      relationship with the manifestations or course of agranulocytosis. In contrast, a
      significantly negative association was found between age of patients and the
      percentage of increase in neutrophil count. Administration of human granulocyte
      colony-stimulating factor did not significantly enhance the recovery of the
      process or the restoration of leucocytes count, suggesting a limited utility in
      this type of agranulocytosis. 

PMID- 25845588
TI  - Reprint of: A healthy island blue space: From space of detention to site of
      sanctuary.
AB  - Island blue spaces are associated with restorative potential, but few studies
      examine this proposition when an island's use has changed over time. We examine
      Rotoroa Island (near Auckland, New Zealand) where, for almost a century, the
      Salvation Army ran an alcohol treatment facility. The island's relative isolation
      was central to its mixed therapeutic and carceral roles. Following change in
      treatment ideologies, the facility closed in 2005. It subsequently re-opened as a
      reserve for recreation, remembrance and environmental restoration. Our analysis
      focuses on the enabling resources at Rotoroa across these two eras, in the
      context of different constructions of healthy island blue space.

PMID- 25845589
TI  - A universal strategy for regulating mRNA translation in prokaryotic and
      eukaryotic cells.
AB  - We describe a simple strategy to control mRNA translation in both prokaryotic and
      eukaryotic cells which relies on a unique protein-RNA interaction. Specifically,
      we used the Pumilio/FBF (PUF) protein to repress translation by binding in
      between the ribosome binding site (RBS) and the start codon (in Escherichia
      coli), or by binding to the 5' untranslated region of target mRNAs (in mammalian
      cells). The design principle is straightforward, the extent of translational
      repression can be tuned and the regulator is genetically encoded, enabling the
      construction of artificial signal cascades. We demonstrate that this approach can
      also be used to regulate polycistronic mRNAs; such regulation has rarely been
      achieved in previous reports. Since the regulator used in this study is a modular
      RNA-binding protein, which can be engineered to target different 8-nucleotide RNA
      sequences, our strategy could be used in the future to target endogenous mRNAs
      for regulating metabolic flows and signaling pathways in both prokaryotic and
      eukaryotic cells. 

PMID- 25845590
TI  - Splicing factor SRSF1 negatively regulates alternative splicing of MDM2 under
      damage.
AB  - Genotoxic stress induces alternative splicing of the oncogene MDM2 generating
      MDM2-ALT1, an isoform attributed with tumorigenic properties. However, the
      mechanisms underlying this event remain unclear. Here we explore MDM2 splicing
      regulation by utilizing a novel minigene that mimics endogenous MDM2 splicing in
      response to UV and cisplatinum-induced DNA damage. We report that exon 11 is
      necessary and sufficient for the damage-specific alternative splicing of the MDM2
      minigene and that the splicing factor SRSF1 binds exon 11 at evolutionarily
      conserved sites. Interestingly, mutations disrupting this interaction proved
      sufficient to abolish the stress-induced alternative splicing of the MDM2
      minigene. Furthermore, SRSF1 overexpression promoted exclusion of exon 11, while
      its siRNA-mediated knockdown prevented the stress-induced alternative splicing of
      endogenous MDM2. Additionally, we observed elevated SRSF1 levels under stress and
      in tumors correlating with the expression of MDM2-ALT1. Notably, we demonstrate
      that MDM2-ALT1 splicing can be blocked by targeting SRSF1 sites on exon 11 using
      antisense oligonucleotides. These results present conclusive evidence supporting
      a negative role for SRSF1 in MDM2 alternative splicing. Importantly, we define
      for the first time, a clear-cut mechanism for the regulation of damage-induced
      MDM2 splicing and present potential strategies for manipulating MDM2 expression
      via splicing modulation. 

PMID- 25845591
TI  - Heat-induced ribosome pausing triggers mRNA co-translational decay in Arabidopsis
      thaliana.
AB  - The reprogramming of gene expression in heat stress is a key determinant to
      organism survival. Gene expression is downregulated through translation
      initiation inhibition and release of free mRNPs that are rapidly degraded or
      stored. In mammals, heat also triggers 5'-ribosome pausing preferentially on
      transcripts coding for HSC/HSP70 chaperone targets, but the impact of such
      phenomenon on mRNA fate remains unknown. Here, we provide evidence that, in
      Arabidopsis thaliana, heat provokes 5'-ribosome pausing leading to the XRN4
      mediated 5'-directed decay of translating mRNAs. We also show that hindering
      HSC/HSP70 activity at 20 degrees C recapitulates heat effects by inducing
      ribosome pausing and co-translational mRNA turnover. Strikingly, co-translational
      decay targets encode proteins with high HSC/HSP70 binding scores and hydrophobic
      N-termini, two characteristics that were previously observed for transcripts most
      prone to pausing in animals. This work suggests for the first time that stress
      induced variation of translation elongation rate is an evolutionarily conserved
      process leading to the polysomal degradation of thousands of 'non-aberrant'
      mRNAs. 

PMID- 25845592
TI  - Molecular crowding enhances facilitated diffusion of two human DNA glycosylases.
AB  - Intracellular space is at a premium due to the high concentrations of
      biomolecules and is expected to have a fundamental effect on how large
      macromolecules move in the cell. Here, we report that crowded solutions promote
      intramolecular DNA translocation by two human DNA repair glycosylases. The
      crowding effect increases both the efficiency and average distance of DNA chain
      translocation by hindering escape of the enzymes to bulk solution. The increased
      contact time with the DNA chain provides for redundant damage patrolling within
      individual DNA chains at the expense of slowing the overall rate of damaged base
      removal from a population of molecules. The significant biological implication is
      that a crowded cellular environment could influence the mechanism of damage
      recognition as much as any property of the enzyme or DNA. 

PMID- 25845593
TI  - Uncoupling histone turnover from transcription-associated histone H3
      modifications.
AB  - Transcription in eukaryotes is associated with two major changes in chromatin
      organization. Firstly, nucleosomal histones are continuously replaced by new
      histones, an event that in yeast occurs predominantly at transcriptionally active
      promoters. Secondly, histones become modified post-translationally at specific
      lysine residues. Some modifications, including histone H3 trimethylation at
      lysine 4 (H3K4me3) and acetylation at lysines 9 (H3K9ac) and 14 (H3K14ac), are
      specifically enriched at active promoters where histones exchange, suggesting a
      possible causal relationship. Other modifications accumulate within transcribed
      regions and one of them, H3K36me3, is thought to prevent histone exchange. Here
      we explored the relationship between these four H3 modifications and histone
      turnover at a few selected genes. Using lysine-to-arginine mutants and a histone
      exchange assay, we found that none of these modifications plays a major role in
      either promoting or preventing histone turnover. Unexpectedly, mutation of H3K56,
      whose acetylation occurs prior to chromatin incorporation, had an effect only
      when introduced into the nucleosomal histone. Furthermore, we used various
      genetic approaches to show that histone turnover can be experimentally altered
      with no major consequence on the H3 modifications tested. Together, these results
      suggest that transcription-associated histone turnover and H3 modification are
      two correlating but largely independent events. 

PMID- 25845594
TI  - Specificity of the ModA11, ModA12 and ModD1 epigenetic regulator N(6)-adenine DNA
      methyltransferases of Neisseria meningitidis.
AB  - Phase variation (random ON/OFF switching) of gene expression is a common feature
      of host-adapted pathogenic bacteria. Phase variably expressed N(6)-adenine DNA
      methyltransferases (Mod) alter global methylation patterns resulting in changes
      in gene expression. These systems constitute phase variable regulons called
      phasevarions. Neisseria meningitidis phasevarions regulate genes including
      virulence factors and vaccine candidates, and alter phenotypes including
      antibiotic resistance. The target site recognized by these Type III N(6)-adenine
      DNA methyltransferases is not known. Single molecule, real-time (SMRT) methylome
      analysis was used to identify the recognition site for three key N. meningitidis
      methyltransferases: ModA11 (exemplified by M.NmeMC58I) (5'-CGY M6A: G-3'), ModA12
      (exemplified by M.Nme77I, M.Nme18I and M.Nme579II) (5'-AC M6A: CC-3') and ModD1
      (exemplified by M.Nme579I) (5'-CC M6A: GC-3'). Restriction inhibition assays and
      mutagenesis confirmed the SMRT methylome analysis. The ModA11 site is complex and
      atypical and is dependent on the type of pyrimidine at the central position, in
      combination with the bases flanking the core recognition sequence 5'-CGY M6A: G
      3'. The observed efficiency of methylation in the modA11 strain (MC58) genome
      ranged from 4.6% at 5'-GCGC M6A: GG-3' sites, to 100% at 5'-ACGT M6A: GG-3'
      sites. Analysis of the distribution of modified sites in the respective genomes
      shows many cases of association with intergenic regions of genes with altered
      expression due to phasevarion switching. 

PMID- 25845595
TI  - Reconstructing genome-scale metabolic models with merlin.
AB  - The Metabolic Models Reconstruction Using Genome-Scale Information (merlin) tool
      is a user-friendly Java application that aids the reconstruction of genome-scale
      metabolic models for any organism that has its genome sequenced. It performs the
      major steps of the reconstruction process, including the functional genomic
      annotation of the whole genome and subsequent construction of the portfolio of
      reactions. Moreover, merlin includes tools for the identification and annotation
      of genes encoding transport proteins, generating the transport reactions for
      those carriers. It also performs the compartmentalisation of the model,
      predicting the organelle localisation of the proteins encoded in the genome and
      thus the localisation of the metabolites involved in the reactions promoted by
      such enzymes. The gene-proteins-reactions (GPR) associations are automatically
      generated and included in the model. Finally, merlin expedites the transition
      from genomic data to draft metabolic models reconstructions exported in the SBML
      standard format, allowing the user to have a preliminary view of the biochemical
      network, which can be manually curated within the environment provided by merlin.

PMID- 25845596
TI  - The EMBL-EBI bioinformatics web and programmatic tools framework.
AB  - Since 2009 the EMBL-EBI Job Dispatcher framework has provided free access to a
      range of mainstream sequence analysis applications. These include sequence
      similarity search services (https://www.ebi.ac.uk/Tools/sss/) such as BLAST,
      FASTA and PSI-Search, multiple sequence alignment tools
      (https://www.ebi.ac.uk/Tools/msa/) such as Clustal Omega, MAFFT and T-Coffee, and
      other sequence analysis tools (https://www.ebi.ac.uk/Tools/pfa/) such as
      InterProScan. Through these services users can search mainstream sequence
      databases such as ENA, UniProt and Ensembl Genomes, utilising a uniform web
      interface or systematically through Web Services interfaces
      (https://www.ebi.ac.uk/Tools/webservices/) using common programming languages,
      and obtain enriched results with novel visualisations. Integration with EBI
      Search (https://www.ebi.ac.uk/ebisearch/) and the dbfetch retrieval service
      (https://www.ebi.ac.uk/Tools/dbfetch/) further expands the usefulness of the
      framework. New tools and updates such as NCBI BLAST+, InterProScan 5 and
      PfamScan, new categories such as RNA analysis tools
      (https://www.ebi.ac.uk/Tools/rna/), new databases such as ENA non-coding,
      WormBase ParaSite, Pfam and Rfam, and new workflow methods, together with the
      retirement of depreciated services, ensure that the framework remains relevant to
      today's biological community. 

PMID- 25845597
TI  - A common tRNA modification at an unusual location: the discovery of wyosine
      biosynthesis in mitochondria.
AB  - Establishment of the early genetic code likely required strategies to ensure
      translational accuracy and inevitably involved tRNA post-transcriptional
      modifications. One such modification, wybutosine/wyosine is crucial for
      translational fidelity in Archaea and Eukarya; yet it does not occur in Bacteria
      and has never been described in mitochondria. Here, we present genetic, molecular
      and mass spectromery data demonstrating the first example of wyosine in
      mitochondria, a situation thus far unique to kinetoplastids. We also show that
      these modifications are important for mitochondrial function, underscoring their
      biological significance. This work focuses on TyW1, the enzyme required for the
      most critical step of wyosine biosynthesis. Based on molecular phylogeny, we
      suggest that the kinetoplastids pathways evolved via gene duplication and
      acquisition of an FMN-binding domain now prevalent in TyW1 of most eukaryotes.
      These findings are discussed in the context of the extensive U-insertion RNA
      editing in trypanosome mitochondria, which may have provided selective pressure
      for maintenance of mitochondrial wyosine in this lineage. 

PMID- 25845598
TI  - A functional screen identifies miRNAs that inhibit DNA repair and sensitize
      prostate cancer cells to ionizing radiation.
AB  - MicroRNAs (miRNAs) have been implicated in DNA repair pathways through
      transcriptional responses to DNA damaging agents or through predicted miRNA
      regulation of DNA repair genes. We hypothesized that additional DNA damage
      regulating miRNAs could be identified by screening a library of 810 miRNA
      mimetics for the ability to alter cellular sensitivity to ionizing radiation
      (IR). A prostate cancer Metridia luciferase cell model was applied to examine the
      effects of individual miRNAs on IR sensitivity. A large percentage of miRNA
      mimetics were found to increase cellular sensitivity to IR, while a smaller
      percentage were protective. Two of the most potent IR sensitizing miRNAs, miR-890
      and miR-744-3p, significantly delayed IR induced DNA damage repair. Both miRNAs
      inhibited the expression of multiple components of DNA damage response and DNA
      repair. miR-890 directly targeted MAD2L2, as well as WEE1 and XPC, where miR-744
      3p directly targeted RAD23B. Knock-down of individual miR-890 targets by siRNA
      was not sufficient to ablate miR-890 radiosensitization, signifying that miR-890
      functions by regulating multiple DNA repair genes. Intratumoral delivery of miR
      890 mimetics prior to IR therapy significantly enhanced IR therapeutic efficacy.
      These results reveal novel miRNA regulation of DNA repair and identify miR-890 as
      a potent IR sensitizing agent. 

PMID- 25845599
TI  - Nuclear pore components affect distinct stages of intron-containing gene
      expression.
AB  - Several nuclear pore-associated factors, including the SUMO-protease Ulp1, have
      been proposed to prevent the export of intron-containing messenger
      ribonucleoparticles (mRNPs) in yeast. However, the molecular mechanisms of this
      nuclear pore-dependent mRNA quality control, including the sumoylated targets of
      Ulp1, have remained unidentified. Here, we demonstrate that the apparent 'pre
      mRNA leakage' phenotype arising upon ULP1 inactivation is shared by sumoylation
      mutants of the THO complex, an early mRNP biogenesis factor. Importantly, we
      establish that alteration of THO complex activity differentially impairs the
      expression of intronless and intron-containing reporter genes, rather than
      triggering bona fide 'pre-mRNA leakage'. Indeed, we show that the presence of
      introns within THO target genes attenuates the effect of THO inactivation on
      their transcription. Epistasis analyses further clarify that different nuclear
      pore components influence intron-containing gene expression at distinct stages.
      Ulp1, whose maintenance at nuclear pores depends on the Nup84 complex, impacts on
      THO-dependent gene expression, whereas the nuclear basket-associated Mlp1/Pml39
      proteins prevent pre-mRNA export at a later stage, contributing to mRNA quality
      control. Our study thus highlights the multiplicity of mechanisms by which
      nuclear pores contribute to gene expression, and further provides the first
      evidence that intronic sequences can alleviate early mRNP biogenesis defects. 

PMID- 25845600
TI  - Structures of Escherichia coli DNA adenine methyltransferase (Dam) in complex
      with a non-GATC sequence: potential implications for methylation-independent
      transcriptional repression.
AB  - DNA adenine methyltransferase (Dam) is widespread and conserved among the gamma
      proteobacteria. Methylation of the Ade in GATC sequences regulates diverse
      bacterial cell functions, including gene expression, mismatch repair and
      chromosome replication. Dam also controls virulence in many pathogenic Gram
      negative bacteria. An unexplained and perplexing observation about Escherichia
      coli Dam (EcoDam) is that there is no obvious relationship between the genes that
      are transcriptionally responsive to Dam and the promoter-proximal presence of
      GATC sequences. Here, we demonstrate that EcoDam interacts with a 5-base pair non
      cognate sequence distinct from GATC. The crystal structure of a non-cognate
      complex allowed us to identify a DNA binding element, GTYTA/TARAC (where Y = C/T
      and R = A/G). This element immediately flanks GATC sites in some Dam-regulated
      promoters, including the Pap operon which specifies pyelonephritis-associated
      pili. In addition, Dam interacts with near-cognate GATC sequences (i.e. 3/4-site
      ATC and GAT). Taken together, these results imply that Dam, in addition to being
      responsible for GATC methylation, could also function as a methylation
      independent transcriptional repressor. 

PMID- 25845601
TI  - Gadd45a promotes DNA demethylation through TDG.
AB  - Growth arrest and DNA-damage-inducible protein 45 (Gadd45) family members have
      been implicated in DNA demethylation in vertebrates. However, it remained unclear
      how they contribute to the demethylation process. Here, we demonstrate that
      Gadd45a promotes active DNA demethylation through thymine DNA glycosylase (TDG)
      which has recently been shown to excise 5-formylcytosine (5fC) and 5
      carboxylcytosine (5caC) generated in Ten-eleven-translocation (Tet)-initiated
      oxidative demethylation. The connection of Gadd45a with oxidative demethylation
      is evidenced by the enhanced activation of a methylated reporter gene in HEK293T
      cells expressing Gadd45a in combination with catalytically active TDG and Tet.
      Gadd45a interacts with TDG physically and increases the removal of 5fC and 5caC
      from genomic and transfected plasmid DNA by TDG. Knockout of both Gadd45a and
      Gadd45b from mouse ES cells leads to hypermethylation of specific genomic loci
      most of which are also targets of TDG and show 5fC enrichment in TDG-deficient
      cells. These observations indicate that the demethylation effect of Gadd45a is
      mediated by TDG activity. This finding thus unites Gadd45a with the recently
      defined Tet-initiated demethylation pathway. 

PMID- 25845602
TI  - Formaldehyde inhalation during pregnancy abolishes the development of acute
      innate inflammation in offspring.
AB  - Formaldehyde (FA) is an environmental and occupational pollutant that induces
      programming mechanisms on the acquired immune host defense in offspring when
      exposed during the prenatal period. Hence, here we investigated whether the
      exposure of FA on pregnant rats could affect the development of an innate acute
      lung injury in offspring induced by lipopolissacaride (LPS) injection. Pregnant
      Wistar rats were exposed to FA (0.92 mg/m(3)) or vehicle (distillated water),
      both 1 h/day, 5 days/week, from 1 to 21 days of pregnancy. Non-manipulated rats
      were used as control. After 30 days of birth, the offspring was submitted to
      injection of LPS (Salmonella abortus equi, 5 mg/kg, i.p.). Systemic and lung
      inflammatory parameters were evaluated 24 h later. Exposure to FA during
      gestation abolished the development of acute lung injury in offspring, as
      observed by reduced number of leukocytes in the bronchoalveolar fluid (BAL), in
      the blood and in the bone marrow, and decreased myeloperoxidase activity in the
      lung. Moreover, phagocytes from BAL presented normal phagocytosis, but reduced
      oxidative burst. Alterations on the profile of inflammatory cytokines were
      evidenced by reduced mRNA levels of IL-6 and elevated levels of IL-10 and IFN
      gamma in the lung tissue. Indeed, mRNA levels of toll-likereceptor-4 and nuclear
      factor-kappa B translocation into the nucleus were also reduced. Additionally,
      hyperresponsiveness to methacholine was blunted in the trachea of offspring of FA
      exposed mothers. Together, our data clearly show that FA exposure in the prenatal
      period modifies the programming mechanisms of the innate defense in the offspring
      leading to impaired defense against infections.

PMID- 25845603
TI  - Determination of Urinary PAH Metabolites Using DLLME Hyphenated to Injector Port
      Silylation and GC-MS-MS.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants
      and well-known carcinogens. Hydroxy derivatives of PAH are considered as
      biomarkers of PAH exposure, and there is a need to measure these metabolites at
      low concentrations. So, a precise and eco-friendly analytical method has been
      developed for rapid determination of PAH metabolites. For the first time, a new
      analytical method based on coupling of dispersive liquid-liquid microextraction
      (DLLME) with auto-injector port silylation (auto-IPS) followed by gas
      chromatography-tandem mass spectrometry (GC-MS-MS) analysis is reported for the
      analysis of seven urinary PAH metabolites. Factors affecting DLLME and IPS, such
      as type and volume of extraction and disperser solvent, pH, ionic strength,
      injector port temperature, volume of N,O-bis(trimethylsilyl)trifluoroacetamide
      and type of solvent were investigated. Under optimized conditions, the limit of
      detection and limit of quantification were found to be in the range of 1-9 and 3
      29 ng/mL, respectively. Satisfactory recoveries of metabolites in urine samples
      in the range of 87-95% were found. The developed method has been successfully
      applied for the determination of PAH metabolites in urine samples of exposed
      workers. DLLME-auto-IPS-GC-MS-MS method is time, labor, solvent and reagent
      saving, which can be routinely used for the analysis of urinary PAH metabolites. 

PMID- 25845604
TI  - Volatile substance abuse: fatal overdose with dimethylether.

PMID- 25845606
TI  - What Is the Clinical Utility of Bedside Ultrasonography in the Diagnosis of Acute
      Cardiogenic Pulmonary Edema in the Undifferentiated Dyspneic Patient?

PMID- 25845605
TI  - A conserved proline residue in Dothideomycete Avr4 effector proteins is required
      to trigger a Cf-4-dependent hypersensitive response.
AB  - CfAvr4, a chitin-binding effector protein produced by the Dothideomycete tomato
      pathogen Cladosporium fulvum, protects the cell wall of this fungus against
      hydrolysis by secreted host chitinases during infection. However, in the presence
      of the Cf-4 immune receptor of tomato, CfAvr4 triggers a hypersensitive response
      (HR), which renders the pathogen avirulent. Recently, several orthologues of
      CfAvr4 have been identified from phylogenetically closely related species of
      Dothideomycete fungi. Of these, DsAvr4 from Dothistroma septosporum also triggers
      a Cf-4-dependent HR, but CaAvr4 and CbAvr4 from Cercospora apii and Cercospora
      beticola, respectively, do not. All, however, bind chitin. To identify the
      region(s) and specific amino acid residue(s) of CfAvr4 and DsAvr4 required to
      trigger a Cf-4-dependent HR, chimeric and mutant proteins, in which specific
      protein regions or single amino acid residues, respectively, were exchanged
      between CfAvr4 and CaAvr4 or DsAvr4 and CbAvr4, were tested for their ability to
      trigger an HR in Nicotiana benthamiana plants transgenic for the Cf-4 immune
      receptor gene. Based on this approach, a single region common to CfAvr4 and
      DsAvr4 was determined to carry a conserved proline residue necessary for the
      elicitation of this HR. In support of this result, a Cf-4-dependent HR was
      triggered by mutant CaAvr4 and CbAvr4 proteins carrying an arginine-to-proline
      substitution at this position. This study provides the first step in deciphering
      how Avr4 orthologues from different Dothideomycete fungi trigger a Cf-4-dependent
      HR. 

PMID- 25845607
TI  - Derivation and Internal Validation of the Ebola Prediction Score for Risk
      Stratification of Patients With Suspected Ebola Virus Disease.
AB  - STUDY OBJECTIVE: The current outbreak of Ebola virus disease in West Africa is
      the largest on record and has overwhelmed the capacity of local health systems
      and the international community to provide sufficient isolation and treatment of
      all suspected cases. The goal of this study is to develop a clinical prediction
      model that can help clinicians risk-stratify patients with suspected Ebola virus
      disease in the context of such an epidemic. METHODS: A retrospective analysis was
      performed of patient data collected during routine clinical care at the Bong
      County Ebola Treatment Unit in Liberia during its first 16 weeks of operation.
      The predictive power of 14 clinical and epidemiologic variables was measured
      against the primary outcome of laboratory-confirmed Ebola virus disease, using
      logistic regression to develop a final prediction model. Bootstrap sampling was
      used to assess the internal validity of the model and estimate its performance in
      a simulated validation cohort. RESULTS: Ebola virus disease testing results were
      available for 382 (97%) of 395 patients admitted to the Ebola treatment unit
      during the study period. A total of 160 patients (42%) tested positive for Ebola
      virus disease. Logistic regression analysis identified 6 variables independently
      predictive of laboratory-confirmed Ebola virus disease, including sick contact,
      diarrhea, loss of appetite, muscle pains, difficulty swallowing, and absence of
      abdominal pain. The Ebola Prediction Score, constructed with these 6 variables,
      had an area under the receiver operator characteristic curve of 0.75 (95%
      confidence interval 0.70 to 0.80) for the prediction of laboratory-confirmed
      Ebola virus disease. Patients with higher Ebola Prediction Scores had higher
      likelihoods of laboratory-confirmed Ebola virus disease. CONCLUSION: The Ebola
      Prediction Score can be used by clinicians as an adjunct to current Ebola virus
      disease case definitions to risk-stratify patients with suspected Ebola virus
      disease. Clinicians can use this new tool for the purpose of cohorting patients
      within the suspected-disease ward of an Ebola treatment unit or community-based
      isolation center to prevent nosocomial infection or as a triage tool when patient
      numbers overwhelm available capacity. Given the inherent limitations of clinical
      prediction models, however, a low-cost, point-of-care test that can rapidly and
      definitively exclude Ebola virus disease in patients should be a research
      priority.

PMID- 25845608
TI  - Rates of residual disease with close but negative margins in breast cancer
      surgery.
AB  - OBJECTIVES: A recent multidisciplinary consensus defined an adequate breast
      cancer margin as no ink on tumor. The purpose of this study was to analyze rates
      of residual disease at re-excision by margin width. MATERIALS AND METHODS: A
      prospective database at a single institution was reviewed from 2000 to 2012.
      Institutional protocol had been to perform re-excision surgery when margins were
      <2 millimeters (mm). RESULTS: There were 2520 procedures. Re-excision surgery was
      performed for 12% of breast conserving therapy (BCT) procedures and 2% of
      mastectomies; residual disease was present in 38% and 26%, respectively. The
      rates of residual disease for all patients with positive, 0.1-0.9 mm, and 1.0-1.9
      mm margins were 40%, 38%, and 33%, respectively. Age, race, menopause status,
      width of closest final margin, tumor histology, hormone receptor status, triple
      negative disease and presence of lymphovascular invasion (LVI) were not
      significantly associated with the presence of residual disease. The presence of
      multiple margins <2 mm trended toward significance (p = 0.06). Median follow-up
      was 43 months. The five-year local recurrence rates (5-year LR) were 1.1% for
      mastectomy patients and 1.9% for BCT patients. CONCLUSIONS: Breast cancer
      patients with margins of excision <2 mm have a substantial risk of residual
      disease but the rates far exceed LR rates. These findings suggest that using
      residual disease rates to determine the appropriate margin width is not reliable,
      but also serve as a note of caution to track LR rates as institutions conform to
      new national guidelines for margin management.

PMID- 25845614
TI  - Development and microstructure of tooth histotypes in the blue shark, Prionace
      glauca (Carcharhiniformes: Carcharhinidae) and the great white shark, Carcharodon
      carcharias (Lamniformes: Lamnidae).
AB  - Elasmobranchs exhibit two distinct arrangements of mineralized tissues in the
      teeth that are known as orthodont and osteodont histotypes. Traditionally, it has
      been said that orthodont teeth maintain a pulp cavity throughout tooth
      development whereas osteodont teeth are filled with osteodentine and lack a pulp
      cavity when fully developed. We used light microscopy, scanning electron
      microscopy, and high-resolution micro-computed tomography to compare the
      structure and development of elasmobranch teeth representing the two histotypes.
      As an example of the orthodont histotype, we studied teeth of the blue shark,
      Prionace glauca (Carcharhiniformes: Carcharhinidae). For the osteodont histotype,
      we studied teeth of the great white shark, Carcharodon carcharias (Lamniformes:
      Lamnidae). We document similarities and differences in tooth development and the
      microstructure of tissues in these two species and review the history of
      definitions and interpretations of elasmobranch tooth histotypes. We discuss a
      possible correlation between tooth histotype and tooth replacement and review the
      history of histotype differentiation in sharks. We find that contrary to a long
      held misconception, there is no orthodentine in the osteodont teeth of C.
      carcharias.

PMID- 25845615
TI  - Concurrent administration of sexual assault prevention and risk reduction
      programming: outcomes for women.
AB  - The present study describes the 4- and 7-month postintervention outcomes of a
      sexual assault risk reduction program for women, which was part of an evaluation
      that included a prevention program for men. Relative to the control group,
      participants evidenced more relational sexual assertiveness and self-protective
      behavior, and were more likely to indicate that they utilized active verbal and
      physical self-defense strategies. Whether or not women experienced subsequent
      victimization did not differ between groups. Relative to control group women who
      were victimized, program participants who were victimized between the 4- and 7
      month follow-up blamed the perpetrator more and evidenced less self-blame. 

PMID- 25845616
TI  - The struggle to address woman battering in Slovakia: stories from service
      providers.
AB  - Following the fall of communism, Slovakia found itself in a challenging position:
      to openly acknowledge the existence of intimate partner violence (IPV) and its
      disproportionate effect on women and children without an infrastructure to
      address victim safety, and provide resources and legal help. With collaboration
      with non-governmental organizations (NGOs), the government responded by
      developing shelters and introducing legislation that criminalized IPV and created
      social services for victims. To assess implementation efforts, we conducted in
      depth interviews with governmental officials and NGO personnel who provide
      services for battered women. We focus on the operation and efficacy of shelters
      to discover what services are most needed for battered women, the criminal
      justice system's response to IPV, and what long-range goals will facilitate more
      permanent solutions to the social problem of violence against women in Slovakia. 

PMID- 25845617
TI  - Community economic status and intimate partner violence against women in
      bangladesh: compositional or contextual effects?
AB  - In this research, we used a multi-level contextual-effects analysis to
      disentangle the household- and community-level associations between income and
      intimate partner violence (IPV) against women in Bangladesh. Our analyses of data
      from 2,668 women interviewed as part of the World Health Organization (WHO) multi
      country study on women's health and domestic violence against women showed that
      household income was negatively associated with women's risk of experiencing IPV.
      Controlling for residence in a low-income household, living in a low-income
      community was not associated with women's risk of experiencing IPV. These results
      support a household-level, not community-level, relationship between income and
      IPV in Bangladesh. 

PMID- 25845618
TI  - Qualitative point-of-care D-dimer testing compared with quantitative D-dimer
      testing in excluding pulmonary embolism in primary care.
AB  - BACKGROUND: General practitioners can safely exclude pulmonary embolism (PE) by
      using the Wells PE rule combined with D-dimer testing. OBJECTIVE: To compare the
      accuracy of a strategy using the Wells rule combined with either a qualitative
      point-of-care (POC) D-dimer test performed in primary care or a quantitative
      laboratory-based D-dimer test. METHODS: We used data from a prospective cohort
      study including 598 adults suspected of PE in primary care in the Netherlands.
      General practitioners scored the Wells rule and carried out a qualitative POC
      test. All patients were referred to hospital for reference testing. We obtained
      quantitative D-dimer test results as performed in hospital laboratories. The
      primary outcome was the prevalence of venous thromboembolism in low-risk
      patients. RESULTS: Prevalence of PE was 12.2%. POC D-dimer test results were
      available in 582 patients (97%). Quantitative test results were available in 401
      patients (67%). We imputed results in 197 patients. The quantitative test and POC
      test missed one (0.4%) and four patients (1.5%), respectively, with a negative
      strategy (Wells <= 4 points and D-dimer test negative) (P = 0.20). The POC test
      could exclude 23 more patients (4%) (P = 0.05). The sensitivity and specificity
      of the Wells rule combined with a POC test were 94.5% and 51.0% and, combined
      with a quantitative test, 98.6% and 47.2%, respectively. CONCLUSIONS: Combined
      with the Wells PE rule, both tests are safe to use in excluding PE. The
      quantitative test seemed to be safer than the POC test, albeit not statistically
      significant. The specificity of the POC test was higher, resulting in more
      patients in whom PE could be excluded.

PMID- 25845619
TI  - Chemokine CX3CL1 and its receptor CX3CR1 are associated with human
      atherosclerotic lesion volnerability.
AB  - BACKGROUND: CX3CL1 and its receptor CX3CR1 have been emphasized in
      atherosclerosis recently. In this study we investigated the role of the
      chemokines CX3CL1 and their receptor CX3CR1 in atherogenesis and identified
      whether the genetic variations in CX3CL1 and CX3CR1 impacted the atherosclerosis
      process in coronary artery disease (CAD) or not. METHODS: CX3CL1/CX3CR1
      expression in coronary and carotid artery specimens were analysed by
      immunohistochemistry. CX3CR1 expression on CD4(+) CD28(-) T cells was analysed by
      flow cytometry. We also screened for CX3CL1/CX3CR1 sequence variations selected
      from the hapmap database and examined the association between CX3CL1/CX3CR1 and
      CAD in the Chinese Han population. RESULTS: Immunohistochemical staining of
      tissue from CAD patients showed increased CX3CL1/CX3CR1 expression in
      atherosclerotic coronary and carotid artery plaques compared with normal
      arteries. CX3CL1/CX3CR1 expression was correlated with the severity of the
      atherosclerosis lesion. Patients with CAD also showed an increased number of
      CX3CR1(+) CD4(+) CD28(-) T cells. Compared with their corresponding wild-type
      genotypes, CX3CL1 rs170364 and CX3CR1 rs17793056 were associated with increased
      susceptibility to CAD. CONCLUSIONS: CX3CL1 and CX3CR1 may contribute to the
      formation of coronary atherosclerotic plaque in CAD.CX3CL1 rs170364 and CX3CR1
      rs17793056 polymorphisms may be independent genetic risk factors for CAD.

PMID- 25845620
TI  - Surviving the heat: heterogeneity of response in Saccharomyces cerevisiae
      provides insight into thermal damage to the membrane.
AB  - Environmental heat stress impacts on the physiology and viability of microbial
      cells with concomitant implications for microbial activity and diversity.
      Previously, it has been demonstrated that gradual heating of Saccharomyces
      cerevisiae induces a degree of thermal resistance, whereas a heat shock results
      in a high level of cell death. Here, we show that the impact of exogenous
      nutrients on acquisition of thermal resistance differs between strains. Using
      single-cell methods, we demonstrate the extent of heterogeneity of the heat
      stress response within populations of yeast cells and the presence of
      subpopulations that are reversibly damaged by heat stress. Such cells represent
      potential for recovery of entire populations once stresses are removed. The
      results show that plasma membrane permeability and potential are key factors
      involved in cell survival, but thermal resistance is not related to homeoviscous
      adaptation of the plasma membrane. These results have implications for growth and
      regrowth of populations experiencing environmental heat stress and our
      understanding of impacts at the level of the single cell. Given the important
      role of microbes in biofuel production and bioremediation, a thorough
      understanding of the impact of stress responses of populations and individuals is
      highly desirable. 

PMID- 25845621
TI  - Incarceration and injection drug use in Baltimore, Maryland.
AB  - AIMS: There is limited longitudinal research examining incarceration and
      subsequent changes in drug use among people who inject drugs (PWID) in the United
      States. The objective of the current study was to characterize the frequency of
      incarceration and estimate the association between incarceration and subsequent
      injection drug use among current and former PWIDs in one US city. DESIGN: ALIVE
      (AIDS Linked to the Intravenous Experience) is a prospective cohort study of
      current and former PWIDs, with semi-annual follow-up occurring since 1988.
      SETTING: Baltimore, Maryland, USA. PARTICIPANTS: A total of 3245 participants
      with 48 738 study visits were included. Participants enrolled from 1988 to 2012
      with a median of 13 follow-up visits per participant (Interquartile range = 7
      25). MEASUREMENTS: Incarcerations were defined as any self-reported jail or
      prison stays in the previous 6 months that were >=7 days or longer. The primary
      outcome was defined as any self-reported injection drug use in the previous 6
      months. FINDINGS: At baseline, 29% were female, 90% African American and 33% HIV
      positive. Fifty-seven per cent of participants experienced at least one
      incarceration episode. After adjusting for confounders, there was a positive
      association between incarceration and subsequent injection drug use [adjusted
      odds ratio (AOR) = 1.48, 95% confidence interval (CI) = 1.37-1.59]; however,
      stratified analysis showed that the effect was restricted to those who were not
      injecting at the time of incarceration (AOR = 2.11, 95% CI = 1.88-2.37).
      CONCLUSIONS: In the United States, incarceration of people who had previously
      stopped injecting drugs appears to be associated with an increased risk of
      subsequent injecting.

PMID- 25845622
TI  - Emergency peripartum hysterectomy: results from the prospective Nordic Obstetric
      Surveillance Study (NOSS).
AB  - OBJECTIVE: To assess the prevalence and risk factors of emergency peripartum
      hysterectomy. DESIGN: Nordic collaborative study. POPULATION: 605 362 deliveries
      across the five Nordic countries. METHODS: We collected data prospectively from
      patients undergoing emergency peripartum hysterectomy within 7 days of delivery
      from medical birth registers and hospital discharge registers. Control
      populations consisted of all other women delivering on the same units during the
      same time period. MAIN OUTCOME MEASURES: Emergency peripartum hysterectomy rate.
      RESULTS: The total number of emergency peripartum hysterectomies reached 211,
      yielding an incidence rate of 3.5/10 000 (95% confidence interval 3.0-4.0)
      births. Finland had the highest prevalence (5.1) and Norway the lowest (2.9).
      Primary indications included an abnormally invasive placenta (n = 91, 43.1%),
      atonic bleeding (n = 69, 32.7%), uterine rupture (n = 31, 14.7%), other bleeding
      disorders (n = 12, 5.7%), and other indications (n = 8, 3.8%). The delivery mode
      was cesarean section in nearly 80% of cases. Previous cesarean section was
      reported in 45% of women. Both preterm and post-term birth increased the risk for
      emergency peripartum hysterectomy. The number of stillbirths was substantially
      high (70/1000), but the case fatality rate stood at 0.47% (one death, maternal
      mortality rate 0.17/100 000 deliveries). CONCLUSIONS: A combination of
      prospective data collected from clinicians and information gathered from register
      based databases can yield valuable data, improving the registration accuracy for
      rare, near-miss cases. However, proper and uniform clinical guidelines for the
      use of well-defined international diagnostic codes are still needed.

PMID- 25845623
TI  - A recombinant rabies virus expressing a phosphoprotein-eGFP fusion is rescued and
      applied to the rapid virus neutralization antibody assay.
AB  - Rabies remains a worldwide concern, and dogs are a major vector for rabies virus
      (RABV) transmission. Vaccination is used in China to control the spread of rabies
      in dogs, a practice which necessitates effective, efficient, and high-throughput
      methods to confirm vaccination. The current rapid fluorescent focus inhibition
      test (RFFIT) method to measure virus-neutralizing antibody titers in the serum
      involves multiple steps, and more efficient methods are needed to match the
      increasing demand for this type of monitoring. In this study, based on the
      parental rRC-HL strain, a recombinant RABV rRV-eGFP expressing enhanced green
      fluorescent protein (eGFP) fused with RABV P protein was generated by a reverse
      genetic technique. The rRV-eGFP grew stably and successfully expressed P-eGFP
      fusion in Neuro-2A (NA) host cells. Furthermore, the P protein was shown to co
      localize with eGFP in rRV-eGFP-infected NA cells. Since eGFP is easily detected
      in infected cells under a fluorescence microscope, rRV-eGFP could be used to
      establish a more rapid virus-neutralizing antibody titers assay based on RFFIT,
      designated as the RFFIT-eGFP method. From 69 canine serum samples, the RFFIT-eGFP
      method was shown to be as specific and as sensitive as the RFFIT method,
      suggesting that it might represent a faster tool than conventional RFFIT for
      measuring RABV virus-neutralizing antibody titers in canine sera without
      sacrificing accuracy. 

PMID- 25845624
TI  - Development of an immunochromatographic strip test for rapid detection of lily
      symptomless virus.
AB  - A rapid immunochromatographic strip (ICS) test for specific detection of lily
      symptomless virus (LSV) was developed. The test is based on a double-antibody
      sandwich format and employs two distinct anti-LSV polyclonal antibodies (IgG1 and
      IgG2). The first antibody, IgG1 was used as the detection antibody conjugated to
      colloidal gold and the second antibody, IgG2 was used to as the capture antibody
      at the test line. The performance of the ICS test was evaluated and the results
      obtained were compared with a quadruplex RT-PCR assay. When serial dilutions of
      purified LSV were tested, the LSV detection limit of the ICS test was 6.0 * 10(
      8)mg/mL, which was the same as the quadruplex RT-PCR assay. Relative to
      quadruplex RT-PCR, the specificity and sensitivity of the ICS were 98.6% and
      100%, respectively for field leaf samples. There was significant agreement
      between the results of the ICS and quadruplex RT-PCR tests (kappa = 0.983).
      Compared with conventional lily virus detection methods, our ICS test has many
      advantages: simple, fast, low cost, high sensitivity and specificity, and has
      applications in the laboratory and in the field to detect and control LSV.

PMID- 25845625
TI  - Prediction of human clearance based on animal data and molecular properties.
AB  - Human clearance is often predicted prior to clinical study from in vivo
      preclinical data by virtue of interspecies allometric scaling methods. The aims
      of this study were to determine the important molecular descriptors for the
      extrapolation of animal data to human clearance and further to build a model to
      predict human clearance by combination of animal data and the selected molecular
      descriptors. These important molecular descriptors selected by genetic algorithm
      (GA) were from five classes: quantum mechanical, shadow indices, E-state keys,
      molecular properties, and molecular property counts. Although the data set
      contained many outliers determined by the conventional Mahmood method, the
      variation of most outliers was reduced significantly by our final support vector
      machine (SVM) model. The values of cross-validated correlation coefficient and
      root-mean-squared error (RMSE) for leave-one-out cross-validation (LOOCV) of the
      final SVM model were 0.783 and 0.305, respectively. Meanwhile, the reliability
      and consistency of the final model were also validated by an external test set.
      In conclusion, the SVM model based on the molecular descriptors selected by GA
      and animal data achieved better prediction performance than the Mahmood method.
      This approach can be applied as an improved interspecies allometric scaling
      method in drug research and development. 

PMID- 25845626
TI  - How and why neural and motor variation are related.
AB  - Movements are variable. Recent findings in smooth pursuit eye movements provide
      an explanation for motor variation in terms of the organization of the brain's
      sensory-motor pathways. Variation in sensory estimation is propagated through
      sensory-motor circuits and ultimately causes motor variation. The sensory origin
      of motor variation creates trial-by-trial correlations among the responses of
      neurons at each level of the sensory motor circuit, and between neural and
      behavioral responses. We suggest that motor variation is a compromise between
      multiple competing constraints. The brain strives for motor behavior that is
      'good enough' in the face of constraints that tend to promote variation. 

PMID- 25845627
TI  - C. elegans locomotion: small circuits, complex functions.
AB  - With 302 neurons in the adult Caenorhabditis elegans nervous system, it should be
      possible to build models of complex behaviors spanning sensory input to motor
      output. The logic of the motor circuit is an essential component of such models.
      Advances in physiological, anatomical, and neurogenetic analysis are revealing a
      surprisingly complex signaling network in the worm's small motor circuit. We are
      progressing towards a systems level dissection of the network of premotor
      interneurons, motor neurons, and muscle cells that move the animal forward and
      backward in its environment. 

PMID- 25845629
TI  - Drug release from an oromucosal paste for the selective decontamination of the
      oropharynx (in ICU patients and healthy volunteers).
AB  - Selective oropharyngeal decontamination (SOD) is used in many ICUs in the
      Netherlands and some other European countries. While its clinical effect has been
      studied intensively, no studies have been done to assess the biopharmaceutical
      aspects of the paste, i.e. it is not known which local concentrations exist. For
      this study, five healthy volunteers were subjected to 400mg of the generally used
      paste. Ten ICU patients were treated according to the normal standard in the ICU
      of the University Medical Center Utrecht. Salivary levels of the various
      substances were measured over time using two separate analytical methods. Also
      the microbial burden of the oropharynx was assessed. The results show significant
      variation in release, both ICU patients and healthy volunteers. The
      antimicrobials tobramycin and colistin showed a relatively fast release, while
      nystatin exhibited a controlled release-like pattern. Amphotericin B is hardly
      released from the formulation. The concentration of the antimicrobial agents drop
      to sub-MIC levels relatively fast. From a biopharmaceutical perspective,
      amphotericin B should be replaced by nystatin. The application of the mouth paste
      is subject to massive variation in daily practice; each nurse applies a different
      amount, in a different way. In addition, the formulation is hard to apply and
      unpleasant with regards to the taste and feel for the conscious patients. This is
      not a clinical study, but a study that aimed to give a biopharmaceutical
      justification for SOD Both the clinical practice and the clinically determined
      levels of drugs enable critical evaluation of the outcome of clinical studies
      performed until now. 

PMID- 25845628
TI  - 10-valent pneumococcal non-typeable Haemophilus influenzae protein-D conjugate
      vaccine (PHiD-CV) induces memory B cell responses in healthy Kenyan toddlers.
AB  - Memory B cells are long-lived and could contribute to persistence of humoral
      immunity by maintaining the plasma-cell pool or making recall responses upon re
      exposure to an antigen. We determined the ability of a pneumococcal conjugate
      vaccine to induce anti-pneumococcal memory B cells. Frequencies of memory B cells
      against pneumococcal capsular polysaccharides from serotypes 1, 6B, 14, 19F and
      23F were determined by cultured B cell enzyme-linked immunospot (ELISPOT) in 35
      children aged 12-23 months who received pneumococcal non-typeable Haemophilus
      influenzae protein-D conjugate vaccine (PHiD-CV). The relationships between
      plasma antibodies and memory B cell frequencies were also assessed. After two
      doses of PHiD-CV, the proportion of subjects with detectable memory B cells
      against pneumococcal capsular polysaccharides increased significantly for
      serotypes 1 (3-45%; P < 0.01), 19F (21-66%; P < 0.01) and 23F (13-36%; P = 0.02),
      but not serotypes 6B (24-42%; P = 0.24) and 14 (21-40%; P = 0.06). Correlations
      between antibodies and memory B cells were weak. Carriage of serotype 19F at
      enrolment was associated with poor memory B cell responses against this serotype
      at subsequent time-points (day 30: non-carriers, 82% versus carriers, 0%, P <
      0.01; day 210: non-carriers, 72% versus carriers, 33%, P = 0.07). PHiD-CV is
      capable of inducing memory B cells against some of the component pneumococcal
      capsular polysaccharides. 

PMID- 25845630
TI  - N-stearoyltyrosine dipotassium ameliorates high-fat diet-induced obesity in
      C57BL/6 mice.
AB  - N-stearoyltyrosine dipotassium (NST-2K) as a neuroprotective candidate is
      currently in preclinical studies in China. This study investigated the anti-obese
      effect of NST-2K in high-fat diet-induced obese (DIO) mice. The DIO mice were
      induced from male C57BL/6 mice by feeding high-fat diet for 11-weeks and treated
      orally with NST-2K for other 4 weeks. The treatments of DIO mice with NST-2K at
      60 or 100 mg/kg/day suppressed the body weight gain, decreased both visceral fat
      weight and adipocyte size without influence on food intake. To evaluate the
      effect of NST-2K on lipid metabolism, lipid parameters and several key molecules
      in the plasma, liver, duodenum mucosa and adipose tissue were analyzed. NST-2K
      ameliorated the low-grade inflammation in liver, inhibited pancreatic lipase
      activity in duodenum mucosa, activated beta-oxidation system and reduced
      lipogenesis, thus suppressed lipid accumulation in the liver, reduced adipocyte
      size and improved lipid and carbohydrate metabolism. Overall, without influence
      on food intake, NST-2K ameliorated high-fat diet-induced obesity via suppressing
      liver inflammation, inhibiting dietary fat absorption, promoting lipolysis and
      reducing lipogenesis.

PMID- 25845631
TI  - Development of a simple, biocompatible and cost-effective Inulin
      Diethylenetriamine based siRNA delivery system.
AB  - Small interfering RNAs (siRNAs) have the potential to be of therapeutic value for
      many human diseases. So far, however, a serious obstacle to their therapeutic use
      is represented by the absence of appropriate delivery systems able to protect
      them from degradation and to allow an efficient cellular uptake. In this work we
      developed a siRNA delivery system based on inulin (Inu), an abundant and natural
      polysaccharide. Inu was functionalized via the conjugation with
      diethylenetriamine (DETA) residues to form the complex Inu-DETA. We studied the
      size, surface charge and the shape of the Inu-DETA/siRNA complexes; additionally,
      the cytotoxicity, the silencing efficacy and the cell uptake-mechanisms were
      studied in the human bronchial epithelial cells (16HBE) and in the hepatocellular
      carcinoma derived cells (JHH6). The results presented here indicate that Inu-DETA
      copolymers can effectively bind siRNAs, are highly cytocompatible and, in JHH6,
      can effectively deliver functional siRNAs. Optimal delivery is observed using a
      weight ratio Inu-DETA/siRNA of 4 that corresponds to polyplexes with an average
      size of 600nm and a slightly negative surface charge. Moreover, the uptake and
      trafficking mechanisms, mainly based on micropinocytosis and clatrin mediated
      endocytosis, allow the homogeneous diffusion of siRNA within the cytoplasm of
      JHH6. Notably, in 16 HBE where the trafficking mechanism (caveolae mediated
      endocytosis) does not allow an even distribution of siRNA within the cell
      cytoplasm, no significant siRNA activity is observed. In conclusion, we developed
      a novel inulin-based siRNA delivery system able to efficiently release siRNA in
      JHH6 with negligible cytotoxicity thus opening the way for further testing in
      more complex in vivo models. 

PMID- 25845632
TI  - Design and evaluation of a specific, bi-phase extended release system based on
      differently coated mini-tablets.
AB  - Mini-tablets are gaining great attention as systems capable of being formulated
      into multiple unit systems providing a specific drug release pattern. Within the
      presented research a combined, multiple-unit system, based on different coated
      matrix mini-tablets, has been developed in order to achieve 24-h specific sigmoid
      extended release of the model drug paliperidone. The mini-tablets were based on
      different amounts of polyvinyl acetate/polyvinyl pyrolidone mixture as the matrix
      former, providing extended release, and two different types of pH-dependent,
      acrylic polymer coatings, providing delay in release onset, and thus achieving
      the required specific sigmoid release pattern imposed by the original drug on the
      market. The selected formulation proved to be consistent with pharmacopoeial
      requirements. It was also in vitro similar (f2) to the original drug and the
      theoretical linear release profile, as well as robust and reproducible regarding
      in vitro release in different fasted gastro-intestinal conditions. This is proof
      of concept that 24-h, specific, and almost linear release profile of drugs with
      high solubility can be achieved by employing technology of coated matrix mini
      tablets. 

PMID- 25845633
TI  - Solid self-nanoemulsifying drug delivery system (S-SNEDDS) of darunavir for
      improved dissolution and oral bioavailability: In vitro and in vivo evaluation.
AB  - The current study was aimed to investigate the potential of solid self
      nanoemulsifying drug delivery system (S-SNEDDS) composed of Capmul MCM C8 (oil),
      Tween 80 (surfactant) and Transcutol P (co-surfactant) in improving the
      dissolution and oral bioavailability of darunavir. Liquid self-nanoemulsifying
      drug delivery systems (L-SNEDDS) were developed by using rational blends of
      components with good solubilizing ability for darunavir which were selected based
      on solubility studies, further ternary phase diagram was constructed to determine
      the self-emulsifying region. The prepared L-SNEDDS formulations were evaluated to
      determine the effect of composition on physicochemical parameters like rate of
      emulsification, clarity, phase separation, thermodynamic stability, cloud point
      temperature, globule size and zeta potential. In vitro drug release studies
      showed initial rapid release of about 13.3 +/- 1.4% within 30 min from L-SNEDDS
      followed by slow continuous release of entrapped drug and reached a maximum of
      62.6 +/- 3.5% release at the end of 24h. The globule size analysis revealed the
      formation of nanoemulsion (144 +/- 2.3 nm) from the optimized L-SNEDDS
      formulation and was physically adsorbed onto neusilin US2. In vitro dissolution
      studies indicated faster dissolution of darunavir from the developed S-SNEDDS
      with 3 times greater mean dissolution rate (MDR) compared to pure darunavir.
      Solid state studies concluded the presence of drug in non-crystalline amorphous
      state without any significant interaction of drug with the components of S
      SNEDDS. Furthermore, in vivo pharmacokinetic studies in Wistar rats resulted in
      enhanced values of peak drug concentration (Cmax) for L-SNEDDS (2.98 +/- 0.19
      MUg/mL) and S-SNEDDS (3.7 +/- 0.28 MUg/mL) compared to pure darunavir (1.57 +/-
      0.17 MUg/mL).

PMID- 25845635
TI  - Practice variation in PEG tube placement: trends and predictors among providers
      in the United States.
AB  - BACKGROUND: Enteral access placement is performed among a variety of providers
      and specialties, yet there is a dearth of literature on trends and factors
      related to enteral access placement in the United States. OBJECTIVE: To examine
      trends in the incidence of enteral access procedures performed by
      gastroenterologists in the United States. DESIGN: Retrospective review of upper
      endoscopic procedures that involved PEG tube placement between 2000 and 2010.
      SETTING: Endoscopy sites participating in the Clinical Outcomes Research
      Initiative (CORI). PATIENTS: Patients undergoing upper endoscopy. INTERVENTIONS:
      PEG tube placement. MAIN OUTCOME MEASUREMENTS: Number of PEG tubes placed.
      RESULTS: Overall PEG tube placement by a provider from 2000 to 2010 was 1.7%
      (number of PEG tubes performed/number of upper endoscopies performed), with the
      majority of them being performed by gastroenterologists. Very young and very old,
      non-white racial background (Hispanic: odds ratio [OR] 1.21; 95% CI, 1.13-1.28;
      black: OR 2.24; 95% CI, 2.12-2.36), and men (OR 1.44; 95% CI, 1.39-1.50) were
      patient characteristics associated with greater PEG tube placement. In terms of
      practice setting, PEG tube placement occurred more frequently in community and/or
      health maintenance organization environments and on the East Coast. With respect
      to provider characteristics, male providers were less likely than female
      providers to perform a PEG tube insertion (OR 0.67; 95% CI, 0.64-0.71), and there
      was a trend that as providers were further out of medical school they were less
      likely to perform a PEG tube procedure. Interestingly, surgeons (OR 6.69; 95% CI,
      6.18-7.24) and other providers (non-pediatric/non-general practice) (OR 3.22; 95%
      CI, 2.63-3.94) were more likely to perform PEG tube procedures than were
      gastroenterologists. LIMITATIONS: Participation in CORI is voluntary and may not
      capture data on non-gastroenterologist providers. CONCLUSION: Significant
      practice variation was noted in PEG tube placement in the United States with
      respect to patient and provider characteristics, geographic region, and endoscopy
      settings.

PMID- 25845636
TI  - Gender differences in symptoms of hypothyroidism: a population-based DanThyr
      study.
AB  - OBJECTIVES: We examined the gender-specific symptom prevalences in hypothyroidism
      and in healthy controls and explored the extent to which symptoms indicative of
      thyroid status may be different in women and men. DESIGN AND METHODS: Patients
      newly diagnosed with overt autoimmune hypothyroidism (n = 140) and controls free
      of thyroid disease (n = 560) recruited from the same population participated in a
      population-based study of The Danish Investigation of Iodine Intake and Thyroid
      Diseases (DanThyr). Participants underwent a comprehensive programme including
      blood tests and completion of questionnaires. The gender-specific distribution of
      13 hypothyroidism-associated symptoms and a simple combined score (0-13) was
      explored in conditional uni- and multivariate models taking into account a broad
      spectrum of possible confounders. Diagnostic odds ratios (DORs) were calculated
      as measures for the association between participant status (case vs control) and
      presence of symptoms (yes vs no). RESULTS: In overt autoimmune hypothyroidism,
      94.9% of women and 91.3% of men (P = 0.62) reported at least one of the
      hypothyroidism-associated symptoms, with tiredness as the most common symptom
      followed by dry skin and shortness of breath. In contrast, women free of thyroid
      disease self-reported at least one hypothyroidism-associated symptom considerably
      more often than men (73.7% vs 51.1%, P < 0.001). DORs (+/-SEM) for 0-1/2-3/4-13
      symptoms were 0.07 (0.04-0.10)/2.15 (1.57-2.94)/7.99 (6.15-10.4) in men and 0.21
      (0.16-0.28)/0.62 (0.58-0.66)/1.99 (1.90-2.09) in women. CONCLUSION: The presence
      of symptoms is more indicative for overt autoimmune hypothyroidism in men than in
      women, and presumably persistent symptoms after therapy of hypothyroidism will be
      more common in women.

PMID- 25845637
TI  - Relative stiffness of 3 bandage/splint constructs for stabilization of equine
      midmetacarpal fractures.
AB  - OBJECTIVE: Determine the relative stiffness of 3 bandage/splint constructs
      intended for emergency fracture stabilization. DESIGN: Experimental model. A
      single plane free end deflection model was developed to simulate the forces
      placed on a bandage/splint construct during stabilization of a complete mid
      metacarpal bone fracture. The total deflection of the model in one plane was
      measured following application of 3 different bandage/splint combinations
      including a classic, 3 layered Robert Jones Bandage (RJB) with a splint placed on
      the outside of the bandage (RJB-3), an RJB with splint placed after the first of
      3 bandage layers (RJB-1), and a single layer full limb bandage with external
      splint (SS). Comparisons were made between the deflections of the model with each
      bandage/splint combinations in an effort to determine the most effective method
      for field fracture stabilization. SETTING: Laboratory. ANIMALS: No animals were
      utilized in data collection for this study. Two live horses were utilized during
      the pilot study. INTERVENTIONS: Application of bandage and splint to a model
      intended to simulate the bending force on a lower forelimb fracture in a horse
      MEASUREMENTS AND MAIN RESULTS: Deflection was determined by the difference
      between the height of the model's supported free end before application of a 4.5
      kg weight and at the conclusion of the deflection test. There was no significant
      difference in the amount of deflection between bandage/splint combinations (78 +/
      32 mm (RJB-1), 94 +/- 44 mm (RJB-3), and 93 +/- 33 mm (SS)) CONCLUSIONS: The one
      layer bandage with splint was equivalent to either RJB configuration in the mean
      amount of deflection in the simple model of a fracture.

PMID- 25845638
TI  - Angelica sinensis polysaccharides inhibit endothelial progenitor cell senescence
      through the reduction of oxidative stress and activation of the Akt/hTERT
      pathway.
AB  - CONTEXT: Angelica sinensis (Oliv.) Diels (Apiaceae) polysaccharides (ASP) may
      play a key role in anti-ischemic activity. However, the anti-atherosclerotic
      activity and mechanism are unknown. OBJECTIVE: This study investigated the
      protective effects of ASP against ox-LDL-induced senescence of EPCs and explored
      its underlying molecular mechanisms. MATERIALS AND METHODS: Mononuclear cells
      were isolated from bone marrow (BM) of SD rats and differentiated to EPCs. EPCs
      were exposed to oxidized low-density lipoprotein (ox-LDL, 10 ug/mL, 24 h) and
      incubated with or without high-dose (100 ug/mL, 48 h) or low-dose (20 ug/mL, 48
      h) ASP. Another group of EPCs was pre-treated with Wortmannin (100 nM, 45 min), a
      PI3K/Akt inhibitor. EPC senescence, telomerase activity, and superoxide anion
      levels were assessed using SA-beta-galactosidase staining, telomerase PCR-ELISA
      analysis, and DHE staining, respectively. The expression of related proteins,
      including Akt, p-Akt, hTERT, p-hTERT, and gp91phox, were detected using western
      blot. RESULTS: EPCs (47.3%) were SA-beta-gal positive after treatment by ox-LDL,
      additionally, ox-LDL significantly increased superoxide anion levels (375% versus
      100%), and inhibited telomerase activity (42% versus 100%). However, the pro
      senescent effect of ox-LDL was attenuated about three-fold (16.7%), superoxide
      anion levels were decreased more than two-fold (148%), and telomerase activity
      was recovered partly (88% versus 42%) in the EPCs when treated with ASP (100
      ug/mL). The immunoblotting confirmed that ASP attenuated inhibition of
      phosphorylation of Akt and hTERT induced by ox-LDL and down-regulated increased
      the expression of gp91-phox. Moreover, some effects of ASP were partially
      abrogated in the presence of Wortmannin. DISCUSSION: Ox-LDL induced senescence of
      EPCs via inhibition of telomerase activity, which was influenced by oxidative
      stress and the Akt/hTERT pathway. The inhibition of EPC senescence by ASP could
      be important for potential therapeutics. CONCLUSION: Treatment of EPCs with ASP
      remarkably attenuates the harmful effects of ox-LDL via augmentation of Akt/hTERT
      phosphorylation and inhibition of oxidative stress.

PMID- 25845639
TI  - Screening of antidepressant activity and estimation of quercetin from Coccinia
      indica using TLC densitometry.
AB  - CONTEXT: Coccinia indica Naud (Cucurbitaceae) has been traditionally used for the
      treatment of depression but these claims have not been validated. OBJECTIVES: The
      objective of this study is to investigate antidepressant activity of various
      extracts and fractions of C. indica aerial parts, and to estimate content of
      quercetin in the plant using TLC densitometry. MATERIALS AND METHODS: Coccinia
      indica aerial parts were successively extracted using solvents in increasing
      order of polarity, namely n-hexane, chloroform, methanol, and water. Various
      extracts were evaluated for antidepressant activity at doses of 200 or 400 mg/kg,
      p.o., upon acute administration in mice using the forced swim test (FST). The
      bioactive extract was partitioned successively using solvents in increasing order
      of polarity, namely n-hexane, ethyl acetate, and n-butanol. All fractions were
      also screened for antidepressant activity at doses of 25 or 50 mg/kg, p.o., upon
      acute administration in mice. RESULTS: The methanol extract significantly reduced
      the duration of immobility in FST at dose of 400 mg/kg without affecting
      locomotor activity in open field test, thus, confirmed its antidepressant
      activity, which was statistically equivalent to the standard drug (imipramine, 15
      mg/kg, i.p.). Ethyl acetate fraction (EAF) exhibited antidepressant activity at
      50 mg/kg. Comparative TLC fingerprint studies confirmed the presence of quercetin
      in methanol extract and EAF. Quercetin was used as a chemical marker to
      standardize C. indica aerial parts using the validated TLC densitometric method,
      and the content of quercetin was found to be 0.00172% w/w. CONCLUSIONS: The
      present studies scientifically validated traditional claims of C. indica for
      antidepressant activity.

PMID- 25845640
TI  - Anticancer activities of Withania somnifera: Current research, formulations, and
      future perspectives.
AB  - CONTEXT: Cancer, being a cause of death for major fraction of population
      worldwide, is one of the most studied diseases and is being investigated for the
      development of new technologies and more accurate therapies. Still the currently
      available therapies for cancer have many lacunae which affect the patient's
      health severely in the form of side effects. The natural drugs obtained from the
      medicinal plants provide a better alternative to fight against this devastating
      disease. Withania somnifera L. Dunal (Solanaceae), a well-known Ayurvedic
      medicinal plant, has been traditionally used to cure various ailments for
      centuries. OBJECTIVES: Considering the immense potential of W. somnifera, this
      review provides a detail account of its vital phytoconstituents and summarizes
      the present status of the research carried out on its anticancerous activities,
      giving future directions. METHODS: The sources of scientific literature were
      accessed from various electronic databases such as PubMed, Google Scholar,
      Science Direct, and library search. RESULTS: Various parts of W. somnifera
      especially the roots with its unique contents have been proved effective against
      different kinds of cancers. The most active components withanolides and
      withaferins along with a few other metabolites including withanone (WN) and
      withanosides have been reported effective against different types of cancer cell
      lines. CONCLUSION: This herb holds an important place among various anticancer
      medicinal plants. It is very essential to further screen and to investigate
      different formulations for anticancer therapy in vitro as well as in vivo in
      combination with established chemotherapy.

PMID- 25845641
TI  - Chlorogenic acid-enriched extract from Eucommia ulmoides leaves inhibits hepatic
      lipid accumulation through regulation of cholesterol metabolism in HepG2 cells.
AB  - CONTEXT: Eucommia ulmoides Oliver (Eucommiaceae) leaf exhibits beneficial lipid
      lowering and anti-obesity effects. However, the mechanisms remain unknown.
      OBJECTIVE: The objective of this study is to investigate the lipid-lowering
      effects of chlorogenic acid (CGA)-enriched extract from this plant (CAEF) in
      human hepatoma HepG2 cells, focusing on cholesterol metabolism. MATERIALS AND
      METHODS: HepG2 cells were treated with CAEF (10, 20, 25, 40, 60, and 80 mg/L),
      CGA (0.3, 3, 30, 300, and 600 MUmol/L), and simvastatin (0.1, 1, 10, 50, and 100
      MUmol/L) for 24 or 48 h. The cytotoxicity, Oil red O staining, total cholesterol,
      and triacylglycerol in supernatants were determined. The mRNA expression of genes
      involved in cholesterol metabolism was determined with RT-PCR. The protein
      expression of HMG-CoA reductase (HMGCR) was examined by immunocytochemistry and
      western-blot. RESULTS: The IC50 values were 59.2 mg/L for CAEF, 335.9 MUmol/L for
      CGA, and 10.5 MUmol/L for simvastatin. By treating cells with CAEF (25 mg/L), CGA
      (30 MUmol/L), or simvastatin (10 MUmol/L) for 48 h, the efflux of total
      cholesterol and triacylglycerol was increased (CAEF, 4.06- and 31.00-folds; CGA,
      2.94- and 2.17-folds; and simvastatin, 3.94- and 24.67-folds), and the cellular
      lipid droplets were reduced in Oil red O staining. CAEF and CGA increased mRNA
      expression of ABCA1, CYP7A1, and AMPKalpha2, while CAEF and simvastatin decreased
      SREBP2. However, their effects on LXRalpha mRNA expression were variable.
      Importantly, all drugs significantly inhibited protein expression of HMGCR at
      mRNA and protein levels. DISCUSSION AND CONCLUSION: CAEF is a promising dietary
      supplement to prevent obesity and dyslipidemia and the effects appear to be due,
      at least in part, to regulating cholesterol metabolism through inhibition of
      HMGCR in HepG2 cells.

PMID- 25845642
TI  - T cell regulation by Phlomis lanata protein extracts in mice.
AB  - CONTEXT: Phytopharmacology is a complex but very promising research area. The
      different plant parts and extraction methods may result in opposed effects.
      Phlomis species have been reported for both anti-inflammatory and tonic
      properties. OBJECTIVE: The effect of Phlomis lanata Willd. (Lamiaceae) protein
      extracts on immune cell reactivity was studied in the experimental mouse model.
      MATERIALS AND METHODS: Protein extracts from P. lanata aerial parts were
      fractionated by Q-sepharose ion-exchange chromatography and applied to whole
      spleen cells or T-cell subsets at 5 MUg/ml. Cell growth and cytokine production
      were evaluated after 4 and 2 d of culture using (3)H-thymidine-uptake and ELISA
      techniques, respectively. RESULTS: Among the protein fractions tested, column
      wash proteins (W1) and the fraction eluted using 600 mM NaCl (F6) reduced by 76%
      and increased by 78% spleen cell proliferation, respectively. W1 suppressed
      proliferation of effector T-cells, but stimulated the growth of
      suppressor/regulatory cells by 62-148%. Although W1 stimulated IL-2 and IL-10
      production from total spleen cells, it significantly increased IL-10 (50%) and
      reduced IL-2 (30-50%) production from T-cells, while TNF-alpha release was
      enhanced in CD25(+)CD4(+) by 92% and reduced by 50% in CD25(+)CD8(+) cells. F6
      stimulated whole spleen cell growth, reduced proliferation of CD8(+) and CD25(+)
      cells by approximately 50%, while decreasing by 60-80% TNF-alpha production from
      CD25(-) and CD25(+)CD8(+) cells. DISCUSSION AND CONCLUSION: The suppressive
      activity of W1 could be attributed to IL-10 and TNF-alpha, while the stimulatory
      effect of F6 could be attributed to the inhibition of T-regulatory cells. In the
      same plant, coexisting protein fractions induce both immunostimulatory and
      immunosuppressive activities.

PMID- 25845643
TI  - Compounds from Sedum caeruleum with antioxidant, anticholinesterase, and
      antibacterial activities.
AB  - CONTEXT: This is the first study on the phytochemistry, antioxidant,
      anticholinesterase, and antibacterial activities of Sedum caeruleum L.
      (Crassulaceae). OBJECTIVE: The objective of this study is to isolate the
      secondary metabolites and determine the antioxidant, anticholinesterase, and
      antibacterial activities of S. caeruleum. MATERIALS AND METHODS: Six compounds (1
      6) were isolated from the extracts of S. caeruleum and elucidated using UV, 1D-,
      2D-NMR, and MS techniques. Antioxidant activity was investigated using DPPH(*),
      CUPRAC, and ferrous-ions chelating assays. Anticholinesterase activity was
      determined against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE)
      enzymes using the Ellman method. Antibacterial activity was performed according
      to disc diffusion and minimum inhibitory concentration (MIC) methods. RESULTS:
      Isolated compounds were elucidated as ursolic acid (1), daucosterol (2), beta
      sitosterol-3-O-beta-D-galactopyranoside (3), apigenin (4), apigetrin (5), and
      apiin (6). The butanol extract exhibited highest antioxidant activity in all
      tests (IC50 value: 28.35 +/- 1.22 ug/mL in DPPH assay, IC50 value: 40.83 +/- 2.24
      ug/L in metal chelating activity, and IC50 value: 23.52 +/- 0.44 ug/L in CUPRAC),
      and the highest BChE inhibitory activity (IC50 value: 36.89 +/- 0.15 ug/L).
      Moreover, the chloroform extract mildly inhibited (MIC value: 80 ug/mL) the
      growth of all the tested bacterial strains. DISCUSSION AND CONCLUSION: Ursolic
      acid (1), daucosterol (2), beta-sitosterol-3-O-beta-D-galactopyranoside (3),
      apigenin (4), apigetrin (5), and apiin (6) were isolated from Sedum caeruleum for
      the first time. In addition, a correlation was observed between antioxidant and
      anticholinesterase activities of bioactive ingredients of this plant.

PMID- 25845644
TI  - Low-dose total-body irradiation and alemtuzumab-based reduced-intensity
      conditioning regimen results in durable engraftment and correction of clinical
      disease among children with chronic granulomatous disease.
AB  - HSCT with MAC is associated with durable donor engraftment for patients with CGD;
      however, MAC is limited by high rates of RRT. We used a novel RIC regimen with LD
      TBI (200 cGy * two doses), fludarabine (30 mg/m(2) * three doses), and proximal
      alemtuzumab (0.5 mg/kg/dose * one dose) and unrelated donor grafts for
      consecutive patients with high-risk CGD who were not candidates for MAC at our
      institution. Among four children with CGD transplanted at our institution, three
      PBSC recipients are alive with sustained donor engraftment (median follow-up: two
      yr) and resolution of pre-HSCT active infections while one patient with bone
      marrow graft is alive after graft failure and autologous recovery. RIC may be a
      curative option for children with high-risk CGD.

PMID- 25845645
TI  - Performance of Frozen Density Embedding for Modeling Hole Transfer Reactions.
AB  - We have carried out a thorough benchmark of the frozen density-embedding (FDE)
      method for calculating hole transfer couplings. We have considered 10 exchange
      correlation functionals, 3 nonadditive kinetic energy functionals, and 3 basis
      sets. Overall, we conclude that with a 7% mean relative unsigned error, the PBE
      and PW91 functionals coupled with the PW91k nonadditive kinetic energy functional
      and a TZP basis set constitute the most stable and accurate levels of theory for
      hole transfer coupling calculations. The FDE-ET method is found to be an
      excellent tool for computing diabatic couplings for hole transfer reactions. 

PMID- 25845646
TI  - Role of Toll-like receptor 4 signaling in cutaneous chronic graft-versus-host
      disease.
AB  - Cutaneous damage is one of the characterized manifestations in chronic graft
      versus-host disease (cGVHD). When local effective immunity in the skin is altered
      to a dysimmune reaction, cutaneous injuries occur. Toll-like receptor 4 signaling
      is regarded as a central mediator of inflammation and organ injury. In this
      study, we found that TLR4 mRNA in peripheral blood from patients with cutaneous
      cGVHD was markedly increased compared with that from non-GVHD patients and
      healthy controls. In addition, NF-kappaB expression, TLR4 downstream signaling,
      and TLR4-mediated cytokines, including IL-6 and ICAM-1, were upregulated.
      Moreover, ICAM-1 was widely distributed in skin biopsies from patients with
      cutaneous cGVHD. We also found that LPS induced TLR4-mediated NF-kappaB
      activation and IL-6 and ICAM-1 secretion in human fibroblasts in vitro. Thus,
      TLR4, NF-kappaB, IL-6, and ICAM-1 contribute to the inflammatory response that
      occurs in cutaneous cGVHD, indicating the TLR4 pathway may be a novel target for
      cutaneous cGVHD therapy.

PMID- 25845647
TI  - Selective fusion in adolescent idiopathic scoliosis: a radiographic evaluation of
      risk factors for imbalance.
AB  - STUDY DESIGN: Retrospective database, chart and medical imaging review.
      OBJECTIVES: To report on the outcome and evaluate possible risk factors for
      postoperative complications following selective spinal fusion in patients with
      adolescent idiopathic scoliosis (AIS). MATERIALS AND METHODS: All patients with
      AIS who underwent either a selective thoracic or selective thoracolumbar/lumbar
      spinal fusion at our institution from January 2001 to December 2011 inclusive
      were included in this study. The minimum postoperative follow-up period of all
      patients was 2 years. RESULTS: During the 11-year study period, 157 patients with
      AIS underwent surgery for their progressive spinal deformity. Thirty patients (19
      %) had a selective spinal fusion, with 16 patients (group A) having a selective
      thoracic, and 14 patients (group B) having a selective thoracolumbar/lumbar
      spinal arthrodesis. In both groups the main postoperative complications were
      adding-on (25 % group A, 36 % group B) and coronal decompensation (25 % group A,
      29 % group B). In group A, no statistically significant risk factors for
      postoperative complications were identified. In group B, global coronal balance
      was identified as a significant risk factor for adding-on. Patients with adding
      on had significantly higher coronal balance scores (mean 3.6) than those who did
      not experience adding-on (mean 1.9) (p = 0.03). In addition, those with adding-on
      had a significantly smaller bending lumbar Cobb angle (mean 15) than those
      without adding-on (mean 31.6) (p = 0.015). None of the patients who underwent
      selective spinal fusion required revision surgery. CONCLUSION: Although the
      complication rate after performing a selective spinal fusion is high, the
      revision rate remains low and the debate whether or not to perform a selective
      spinal fusion will continue.

PMID- 25845648
TI  - Conscious Vision in Action.
AB  - It is natural to assume that the fine-grained and highly accurate spatial
      information present in visual experience is often used to guide our bodily
      actions. Yet this assumption has been challenged by proponents of the Two Visual
      Systems Hypothesis (TVSH), according to which visuomotor programming is the
      responsibility of a "zombie" processing stream whose sources of bottom-up spatial
      information are entirely non-conscious (Clark, 2007, 2009; Goodale & Milner,
      1992, 2004a; Milner & Goodale, 1995/2006, 2008). In many formulations of TVSH,
      the role of conscious vision in action is limited to "recognizing objects,
      selecting targets for action, and determining what kinds of action, broadly
      speaking, to perform" (Clark, 2007, p. 570). Our aim in this study is to show
      that the available evidence not only fails to support this dichotomous view but
      actually reveals a significant role for conscious vision in motor programming,
      especially for actions that require deliberate attention. 

PMID- 25845653
TI  - Resveratrol prevents osteoporosis in ovariectomized rats by regulating microRNA
      338-3p.
AB  - Osteoporosis is a disease characterized by loss of bone mass and degeneration of
      the microstructure of bone. Resveratrol (3,5,4-tri-hydroxystilbene; RESV) may
      delay the onset of a variety of age-related diseases. In the present study, an
      ovariectomized female rat model was used to detect the changes in microRNAs
      (miRNAs/miRs) following RESV treatment. Subsequently, the target genes of miRNA
      were predicted using TargetScan software and determined using a dual-luciferase
      reporter assay. Finally, the role of miR-338-3p in the proliferation and
      differentiation of human osteoblast (HOB) cells was confirmed. The predominant
      finding of the present study was the identification of an intact mechanism of the
      effect of RESV in osteoporosis treatment. The results suggested that RESV
      suppresses miR-338-3p, followed by an increase in the expression of runt-related
      transcription factor 2 in HOB cells.

PMID- 25845654
TI  - Bevacizumab did not reduce the risk of anemia associated with chemotherapy: an up
      to-date meta-analysis.
AB  - PURPOSE: The risk of anemia due to bevacizumab-based chemotherapy has not been
      well described, and new randomized controlled trials (RCTs) have been reported in
      recent years. We therefore conducted an up-to-date meta-analysis of RCTs to fully
      characterize the risk of anemia with bevacizumab. METHODS: We carried out an
      electronic search of Medline, Embase, and The Cochrane Central Register of
      Controlled Trials to investigate the effects of RCTs on bevacizumab treatment on
      cancer patients up to October 2014, and random or fixed-effect meta-analytical
      models were used to assess the risk ratio (RR) of anemia due to the use of
      bevacizumab according to the heterogeneity of included studies. RESULTS: A total
      of 13,173 patients were included in this analysis from 18 RCTs. Among those
      patients receiving bevacizumab and chemotherapy, the incidences of all-grade and
      high-grade (grade 3 and above) anemia were 24% (95% confidence interval (CI) 13
      41%) and 4.0% (95% CI 3.0-6.0%), respectively. Bevacizumab-containing therapy did
      not significantly decreased the risk of developing all-grade anemia (RR 0.872,
      95% CI 0.739-1.029, P = 0.104) and high-grade anemia (RR 0.850, 95% CI 0.720
      1.002, P = 0.053), which is not in agreement with previous meta-analysis. On
      subgroup analysis, we did not find significant risk differences based on
      bevacizumab dosage, tumor types, and concomitant drugs. When stratified by dose
      level, a significantly decreased risk of high-grade anemia with bevacizumab was
      obtained in a lower dose level (2.5 mg/kg/week, RR 0.773, 95% CI 0.611-0.978, P =
      0.031) compared to control group. CONCLUSIONS: Bevacizumab did not significantly
      reduce the risk of anemia with chemotherapy in cancer patients.

PMID- 25845655
TI  - The impact of a changed legislation on reporting of adverse drug reactions in
      Sweden, with focus on nurses' reporting.
AB  - PURPOSE: In March 2007, a legislative amendment was issued in Sweden compelling
      nurses to report all suspected adverse drug reactions (ADRs) to the national
      pharmacovigilance system. The aims of this study were to describe the status of
      ADR reporting, before and after the implementation of the legislative changes,
      and to describe the general characteristics of suspected ADRs reported by nurses.
      METHODS: The Swedish pharmacovigilance system during the study period constituted
      six regional centres responsible for the handling of all spontaneous ADR reports
      within their region. In this study, we identified all individual ADR reports from
      2005 and 2010, analysed in depth the ADR reports from two regional centres and
      collated information about the reporter and the nature of the reported ADR.
      RESULTS: From the two regional centres, a total of 898 and 1074 reports were
      submitted in 2005 and 2010 respectively. Nurses submitted 31% (275 reports) of
      the reports in 2005 and 24% (260 reports) in 2010. Nurses' reporting of serious
      ADRs was 3% (seven reports) in 2005 and 7% (17 reports) in 2010 with reporting of
      unlabelled ADRs at 4% (11 reports) in 2005 and 17% (45 reports) in 2010. Most of
      the serious and/or unlabelled reactions were related to vaccine administration
      (14 reports in 2005 and 36 reports in 2010). CONCLUSIONS: The overall ADR
      reporting by nurses did not appear to increase after the change in reporting
      legislation. The proportion of serious and/or unlabelled ADRs reported by nurses
      did however appear to increase during the same period. Taken together, our data
      suggests that further pro-active measures should be considered in order to
      involve nurses in the reporting of suspected ADRs.

PMID- 25845656
TI  - Association between hypnotics use and increased mortality: causation or
      confounding?
AB  - PURPOSE: Many research studies have found associations between benzodiazepines
      and/or z-hypnotics (BZZ) and increasing mortality, leading to a discussion about
      causation or confounding. This study suggests a factor that could produce this
      association through confounding. METHODS: The Norwegian population in 2010
      supplied 8862 deaths ages 41-80 and 898,289 controls. Index dates were added to
      control records which corresponded to death dates. BZZ use was recorded for 2
      years before death/index date. RESULTS: Persons exposed to BZZ were more likely
      (OR = 2.3) to die than those who were not. With proximity of death, increasingly
      larger proportions of the prospective deaths received prescriptions for BZZ,
      until in the last 2 months 40-45% received BZZ. The frequency of BZZ use in
      controls increased with age as opposed to the death cohort where all ages showed
      similar rates of BZZ use. In the last few months before death, the youngest age
      group had an OR = 5.8 for BZZ use while the oldest age group an OR = 1.8,
      adjusted for age and sex. Opioid use showed a similar pattern of increasing use
      near death. CONCLUSIONS: The increased use of BZZ with approaching death is
      consistent with increasing symptomatic treatment in terminal illness. Thus, the
      association of BZZ and mortality is more likely to be due to confounding than to
      causality. Further evidence from this and other research includes similar use
      patterns for other drugs such as opioids, the lack of specificity in cause of
      death and the size of the association regarding age and time to death.

PMID- 25845657
TI  - Inter-individual variation in morphine clearance in children.
AB  - OBJECTIVES: The aim of the study was to determine the extent of inter-individual
      variation in clearance of intravenous morphine in children and to establish which
      factors are responsible for this variation. METHODS: A systematic literature
      review was performed to identify papers describing the clearance of morphine in
      children. The following databases were searched: Medline, Embase, International
      Pharmaceutical Abstracts, CINAHL, and Cochrane library. From the papers, the
      range in plasma clearance and the coefficient of variation (CV) in plasma
      clearance were determined. RESULTS: Twenty-eight studies were identified. After
      quality assessment, 20 studies were included. Only 10 studies gave clearance
      values for individual patients. The majority of the studies were in critically
      ill patients. Inter-individual variability of morphine clearance was observed in
      all age groups, but greatest in critically ill neonates (both preterm and term)
      and infants. In critically ill patients, the CV was 16-97% in preterm neonates,
      24-87% in term neonates, 35 and 134% in infants, 39 and 55% in children, and 74%
      in adolescents. The CV was 37 and 44% respectively in non-critically ill neonates
      and infants. The mean clearance was higher in children (32 and 52 ml min(-1) kg(
      1)) than in neonates (2 to 16 ml min(-1) kg(-1)). CONCLUSIONS: Large inter
      individual variation was seen in morphine clearance values in critically ill
      neonates and infants.

PMID- 25845658
TI  - Psychometric properties of the Five-Digit Test in patients with stroke.
AB  - PURPOSE: To examine the ecological validity, predictive validity, and
      responsiveness of the Five Digit Test (FDT) in patients with stroke. METHODS: We
      included inpatients with stroke (n = 144, 114 and 105 in the ecological validity,
      predictive validity, and responsiveness analysis, respectively) in the study. At
      admission, the FDT and Barthel Index (BI) were assessed; at discharge, the FDT,
      BI, Postural Assessment Scale for Stroke Patients (PASS), and Mobility Subscale
      of the Stroke Rehabilitation Assessment of Movement (MO-STREAM) were assessed.
      RESULTS: In the ecological validity analysis, the scores of the selective and
      alternating attention indices of the FDT were moderately correlated with those of
      the BI at admission and discharge (Spearman rho = -0.38 to -0.45). In the
      predictive validity analysis, the scores of the two attention indices of the FDT
      at admission were moderately correlated with the scores of the BI, PASS, and MO
      STREAM at discharge (rho = -0.33 to -0.45). In the responsiveness analysis, the
      two attention indices of the FDT between admission and discharge had large
      differences (success rate difference = 0.56-0.67, Wilcoxon Z = -5.90 to -6.60).
      CONCLUSION: Our results indicate that the selective and alternating attention
      indices of the FDT have acceptable ecological validity, predictive validity, and
      good responsiveness in patients with stroke. IMPLICATIONS FOR REHABILITATION: The
      Five Digit Test (FDT), an efficient and culture-free assessment tool, has been
      used to assess selective attention and alternating attention The selective index
      and alternating attention index of the FDT showed acceptable ecological validity,
      predictive validity, and good responsiveness in patients with stroke.

PMID- 25845659
TI  - Dietary Polyphenols Promote Growth of the Gut Bacterium Akkermansia muciniphila
      and Attenuate High-Fat Diet-Induced Metabolic Syndrome.
AB  - Dietary polyphenols protect against metabolic syndrome, despite limited
      absorption and digestion, raising questions about their mechanism of action. We
      hypothesized that one mechanism may involve the gut microbiota. To test this
      hypothesis, C57BL/6J mice were fed a high-fat diet (HFD) containing 1% Concord
      grape polyphenols (GP). Relative to vehicle controls, GP attenuated several
      effects of HFD feeding, including weight gain, adiposity, serum inflammatory
      markers (tumor necrosis factor [TNF]alpha, interleukin [IL]-6, and
      lipopolysaccharide), and glucose intolerance. GP lowered intestinal expression of
      inflammatory markers (TNFalpha, IL-6, inducible nitric oxide synthase) and a gene
      for glucose absorption (Glut2). GP increased intestinal expression of genes
      involved in barrier function (occludin) and limiting triglyceride storage
      (fasting-induced adipocyte factor). GP also increased intestinal gene expression
      of proglucagon, a precursor of proteins that promote insulin production and gut
      barrier integrity. 16S rRNA gene sequencing and quantitative PCR of cecal and
      fecal samples demonstrated that GP dramatically increased the growth of
      Akkermansia muciniphila and decreased the proportion of Firmicutes to
      Bacteroidetes, consistent with prior reports that similar changes in microbial
      community structure can protect from diet-induced obesity and metabolic disease.
      These data suggest that GP act in the intestine to modify gut microbial community
      structure, resulting in lower intestinal and systemic inflammation and improved
      metabolic outcomes. The gut microbiota may thus provide the missing link in the
      mechanism of action of poorly absorbed dietary polyphenols. 

PMID- 25845660
TI  - Rapid Repression of ADP Transport by Palmitoyl-CoA Is Attenuated by Exercise
      Training in Humans: A Potential Mechanism to Decrease Oxidative Stress and
      Improve Skeletal Muscle Insulin Signaling.
AB  - Mitochondrial ADP transport may represent a convergence point unifying two
      prominent working models for the development of insulin resistance, as reactive
      lipids (specifically palmitoyl-CoA [P-CoA]) can inhibit ADP transport and
      subsequently increase mitochondrial reactive oxygen species emissions. In the
      current study, we aimed to determine if exercise training in humans diminished P
      CoA attenuation of mitochondrial ADP respiratory sensitivity. Six weeks of
      exercise training increased whole-body glucose homeostasis and skeletal muscle
      Akt signaling and reduced markers of oxidative stress without reducing maximal
      mitochondrial H2O2 emissions. To ascertain if enhanced mitochondrial ADP
      transport contributed to the improvement in the in vivo oxidative state, we
      determined mitochondrial ADP sensitivity in the presence and absence of P-CoA. In
      the absence of P-CoA, exercise training reduced mitochondrial ADP sensitivity. In
      contrast, exercise training increased mitochondrial ADP sensitivity with P-CoA
      present. We further show that P-CoA noncompetitively inhibits mitochondrial ADP
      transport and the ability of ADP to attenuate mitochondrial H2O2 emission.
      Altogether, the current data provide a potential mechanism for how P-CoA
      contributes to insulin resistance and highlight the ability of exercise training
      to diminish P-CoA attenuation in mitochondrial ADP transport. 

PMID- 25845661
TI  - Metabolic Syndrome Abolishes Glucagon-Like Peptide 1 Receptor Agonist Stimulation
      of SERCA in Coronary Smooth Muscle.
AB  - Metabolic syndrome (MetS) doubles the risk of adverse cardiovascular events.
      Glucagon-like peptide 1 (GLP-1) receptor agonists induce weight loss, increase
      insulin secretion, and improve glucose tolerance. Studies in healthy animals
      suggest cardioprotective properties of GLP-1 receptor agonists, perhaps partially
      mediated by improved sarco-endoplasmic reticulum Ca(2+) ATPase (SERCA) activity.
      We examined the acute effect of GLP-1 receptor agonists on coronary smooth muscle
      cells (CSM) enzymatically isolated from lean, healthy Ossabaw miniature swine.
      Intracellular Ca(2+) handling was interrogated with fura-2. The GLP-1 receptor
      agonist exenatide activated SERCA but did not alter other Ca(2+) transporters.
      Further, we tested the hypothesis that chronic, in vivo treatment with GLP-1
      receptor agonist AC3174 would attenuate coronary artery disease (CAD) in swine
      with MetS. MetS was induced in 20 swine by 6 months' feeding of a hypercaloric,
      atherogenic diet. Swine were then randomized (n = 10/group) into placebo or
      AC3174 treatment groups and continued the diet for an additional 6 months. AC3174
      treatment attenuated weight gain, increased insulin secretion, and improved
      glucose tolerance. Intravascular ultrasound and histology showed no effect of
      AC3174 on CAD. MetS abolished SERCA activation by GLP-1 receptor agonists. We
      conclude that MetS confers vascular resistance to GLP-1 receptor agonists,
      partially through impaired cellular signaling steps involving SERCA. 

PMID- 25845663
TI  - Genetic Disruption of Protein Kinase STK25 Ameliorates Metabolic Defects in a
      Diet-Induced Type 2 Diabetes Model.
AB  - Understanding the molecular networks controlling ectopic lipid deposition,
      glucose tolerance, and insulin sensitivity is essential to identifying new
      pharmacological approaches to treat type 2 diabetes. We recently identified
      serine/threonine protein kinase 25 (STK25) as a negative regulator of glucose and
      insulin homeostasis based on observations in myoblasts with acute depletion of
      STK25 and in STK25-overexpressing transgenic mice. Here, we challenged Stk25
      knockout mice and wild-type littermates with a high-fat diet and showed that
      STK25 deficiency suppressed development of hyperglycemia and hyperinsulinemia,
      improved systemic glucose tolerance, reduced hepatic gluconeogenesis, and
      increased insulin sensitivity. Stk25(-/-) mice were protected from diet-induced
      liver steatosis accompanied by decreased protein levels of acetyl-CoA
      carboxylase, a key regulator of both lipid oxidation and synthesis. Lipid
      accumulation in Stk25(-/-) skeletal muscle was reduced, and expression of enzymes
      controlling the muscle oxidative capacity (Cpt1, Acox1, Cs, Cycs, Ucp3) and
      glucose metabolism (Glut1, Glut4, Hk2) was increased. These data are consistent
      with our previous study of STK25 knockdown in myoblasts and reciprocal to the
      metabolic phenotype of Stk25 transgenic mice, reinforcing the validity of the
      results. The findings suggest that STK25 deficiency protects against the
      metabolic consequences of chronic exposure to dietary lipids and highlight the
      potential of STK25 antagonists for the treatment of type 2 diabetes. 

PMID- 25845664
TI  - Perceptions of private market landlords who rent to tenants of a Housing First
      program.
AB  - The rental of housing units by landlords to participants in Housing First (HF)
      programs is critical to the success of these programs. Therefore, it is important
      to understand the experiences of landlords with having these individuals as
      tenants. The paper presents findings of qualitative interviews with 23 landlords
      who rented to tenants from a HF program located in a small city and adjoining
      rural area in eastern Canada and in which approximately 75 % of tenants had been
      housed for at least six consecutive months at 2 years in the program. Findings
      showed that landlords are motivated to rent to HF tenants for financial and pro
      social reasons. They reported holding a range of positive, neutral, and negative
      perceptions of these tenants. They identified problems encountered with some HF
      tenants that included disruptive visitors, conflict with other tenants, constant
      presence in their apartments, and poor upkeep of units. On the other hand,
      landlords perceived HF tenants as being mostly good tenants who are similar to
      their other tenants. Implications for practice in the context of HF programs are
      discussed.

PMID- 25845662
TI  - M2 Macrophage Polarization Mediates Anti-inflammatory Effects of Endothelial
      Nitric Oxide Signaling.
AB  - Endothelial nitric oxide (NO) signaling plays a physiological role in limiting
      obesity-associated insulin resistance and inflammation. This study was undertaken
      to investigate whether this NO effect involves polarization of macrophages toward
      an anti-inflammatory M2 phenotype. Mice with transgenic endothelial NO synthase
      overexpression were protected against high-fat diet (HFD)-induced hepatic
      inflammation and insulin resistance, and this effect was associated with reduced
      proinflammatory M1 and increased anti-inflammatory M2 activation of Kupffer
      cells. In cell culture studies, exposure of macrophages to endothelial NO
      similarly reduced inflammatory (M1) and increased anti-inflammatory (M2) gene
      expression. Similar effects were induced by macrophage overexpression of
      vasodilator-stimulated phosphoprotein (VASP), a key downstream mediator of
      intracellular NO signaling. Conversely, VASP deficiency induced proinflammatory
      M1 macrophage activation, and the transplantation of bone marrow from VASP
      deficient donor mice into normal recipients caused hepatic inflammation and
      insulin resistance resembling that induced in normal mice by consumption of an
      HFD. These data suggest that proinflammatory macrophage M1 activation and
      macrophage-mediated inflammation are tonically inhibited by NO -> VASP signal
      transduction, and that reduced NO -> VASP signaling is involved in the effect of
      HFD feeding to induce M1 activation of Kupffer cells and associated hepatic
      inflammation. Our data implicate endothelial NO -> VASP signaling as a
      physiological determinant of macrophage polarization and show that signaling via
      this pathway is required to prevent hepatic inflammation and insulin resistance. 

PMID- 25845665
TI  - Disclosure experiences of sexual minority college student victims of intimate
      partner violence.
AB  - Although research on disclosure following intimate partner violence (IPV)
      victimization is burgeoning, sexual minority young adults' (lesbian, gay,
      bisexual, queer, questioning, etc.; LGBQ+) experiences have not received equal
      attention. The current study employed the minority stress framework to examine
      disclosure experiences of LGBQ+ college students across the United States
      reporting physical IPV victimization within their current relationship (n = 77).
      Participants completed measures assessing minority stress and IPV disclosure, and
      answered open-ended questions regarding the most and least helpful
      persons/responses to disclosure or reasons for non-disclosure. Results indicated
      that approximately one-third (35 %) of victims disclosed to at least one person,
      with friends being the most common recipients. Thematic analyses indicated that
      talking or listening to the victim was considered the most helpful response and
      not understanding the situation least helpful. Reasons for non-disclosure
      centered on themes of the victims' perception that the IPV was not a big deal.
      Quantitative findings regarding physical IPV disclosure indicated that non
      disclosers experienced greater minority stress than disclosers. The current study
      suggests the presence of differences between sexual minority (i.e., LGBQ
      +persons) and non-sexual minority persons, as well as between LGBQ+ young
      adults/college students and older adults and presents a theoretical structure
      (i.e., minority stress framework) through which these differences may be
      understood.

PMID- 25845668
TI  - Ultrasensitive room temperature NH3 sensor based on a graphene-polyaniline hybrid
      loaded on PET thin film.
AB  - This research was motivated by the need to develop a smart ammonia (NH3) sensor
      based on a flexible polyethylene terephthalate (PET) thin film loaded with a
      reduced graphene oxide-polyaniline (rGO-PANI hybrid) using in situ chemical
      oxidative polymerization. The sensor not only exhibited high sensitivity, good
      selectivity and a fast response at room temperature but was also flexible, cheap
      and had wearable characteristics. 

PMID- 25845666
TI  - The flavonoid nobiletin inhibits tumor growth and angiogenesis of ovarian cancers
      via the Akt pathway.
AB  - Despite its importance, the death rate of ovarian cancer has remained unchanged
      over the past five decades, demanding an improvement in prevention and treatment
      of this malignancy. With no known carcinogens, targeted prevention is currently
      unavailable, and efforts in early detection of this malignancy by screening
      biomarkers have failed. The inhibition of angiogenesis, also known as
      angioprevention, is a promising strategy to limit the growth of solid tumors,
      including ovarian cancers. Nobiletin, a polymethoxy flavonoid compound isolated
      from the tiansheng plant, has been shown to inhibit the growth of multiple types
      of human cancers. However, there are no reports involving the effect on nobiletin
      on human ovarian cancer. The present report shows that nobiletin potently
      decreases the viability of ovarian cancer cells in vitro. However, nobiletin does
      not affect the viability of normal ovarian epithelial cells at <40 uM. The
      antitumor activity of nobiletin was also observed in athymic mouse models and in
      chicken chorioallantoic membrane (CAM) models. The anti-neoplastic activity of
      nobiletin was due to its ability to inhibit angiogenesis. We also studied the
      molecular mechanisms by which nobiletin suppresses angiogenesis. We observed that
      nobiletin inhibits secretion of the key angiogenesis mediators, Akt, HIF-1alpha,
      NF-kappaB and vascular epithelial growth factor (VEGF) by ovarian cancer cells.
      Transient transfection experiments showed that nobiletin inhibits production of
      HIF-1alpha by downregulation of Akt. Such decreased levels of HIF-1alpha were
      responsible for nobiletin-induced suppression of VEGF. Our data suggest that
      nobiletin may be a promising anti-angiogenic agent relevant for therapy of
      ovarian cancers.

PMID- 25845667
TI  - Detection of endothelial progenitor cells in human skin wounds and its
      application for wound age determination.
AB  - Endothelial progenitor cells (EPCs), a newly identified cell type, are bone
      marrow-derived progenitor cells that co-express stem cell markers and vascular
      endothelial growth factor (VEGF) receptor (Flk-1). In this study, a double-color
      immunofluorescence analysis was carried out using anti-CD34 and anti-Flk-1
      antibodies to examine the time-dependent appearance of EPCs, using 52 human skin
      wounds with different wound ages (Group I, 0-1 days; Group II, 2-6 days; Group
      III, 7-14 days; and Group IV, 17-21 days). In wound specimens with an age of less
      than one day, CD34(+)/Flk-1(+) EPCs were not detected. EPCs were initially
      observed in wounds aged two days, and their number was increased in lesions with
      advances in wound age. In morphometrical analysis, the average number of EPCs was
      the highest in the wounds of Group III. Especially, 20 out of 21 wounds aged 7-12
      days had >20 EPCs, and all wound samples with postinfliction intervals of 14-21
      days had <15 EPCs. These observations at least showed that >20 EPCs would
      indicate a wound age of 7-12 days. Taken together, our observations indicate the
      detection of EPCs would be useful for wound age determination.

PMID- 25845669
TI  - Guanine tetrads: an IRMPD spectroscopy, energy resolved SORI-CID, and
      computational study of M(9-ethylguanine)(4)(+) (M = Li, Na, K, Rb, Cs) in the gas
      phase.
AB  - The intrinsic properties of the alkali metal cationized G-tetrads, M(9eG)4(+) (M
      = Li, Na, K, Rb, Cs) composed of 9-ethylguanine (9eG), were studied by a
      combination of mass spectrometric techniques. The gas phase structures were
      probed by infrared multiple photon dissociation (IRMPD) spectroscopy in both the
      fingerprint region (900-1850 cm(-1)) and the N-H/C-H stretching region (2700-3800
      cm(-1)). The gas phase structures were found to be similar for all five complexes
      and most consistent with the metal-centred G-tetrad structure. Energy-resolved
      CID was also used to compare the gas phase stabilities of the G-tetrads and
      showed that Na(9eG)4(+) was more stable than Li(9eG)4(+) followed by the K(+),
      Rb(+), and Cs(+) G-tetrads in order. The experimental energy ordering was
      reproduced by electronic structure calculations of the energies. Furthermore, the
      computations also showed that the lower stability to loss of 9-ethylguanine for
      the Li(+) complex could be due to a strong destabilization of the neutral G
      tetrad due to the persistence toward maximizing the ion-dipole interactions while
      also maintaining hydrogen bonding interactions. 

PMID- 25845671
TI  - The fifty most cited Italian articles in the orthopaedic literature.
AB  - PURPOSES: It is widely known that in Orthopaedics, as in each specialty, the
      academic influence of an article is also determined by the number of times the
      article is cited. The aim of this study was to identify the 50 most frequently
      cited Italian orthopaedics journal articles and to analyse the characteristics
      that might have made them more citable. METHODS: Science Citation Index Expanded
      was searched for the 50 most frequently cited Italian orthopaedics journal
      articles between 1988 and 2013 in the subject category "Orthopaedics". RESULTS:
      The 50 most frequently cited articles were all published in English and were
      published in 12 of the 67 journals in the subject category "Orthopaedics" in the
      Institute for Scientific Information Web Science (Thomson Reuters, New York, New
      York, USA). One half of the articles were published before 2000 and the other
      half later. The number of citations ranged from 423 of the first article (mean
      citation/years 21.15) to 83 of the fiftieth (mean citation/years 16.60). The
      articles were all categorized under orthopaedic field, but each of them spanned
      from orthopaedics to a specific sub-specialty. The majority was clinical articles
      (n = 39), and the most common fields were sport orthopaedic surgery (including
      arthroscopy and cartilage) (n = 19) and biomechanics (n = 12). CONCLUSIONS: This
      list of 50 most frequently cited Italian articles is, to our knowledge,
      significantly important for the general orthopaedic scientific community,
      particularly for the Italian orthopaedic community. Researchers and doctors may
      use this work to make their future publications more influential and citable.

PMID- 25845670
TI  - Autologous bone graft harvesting: a review of grafts and surgical techniques.
AB  - Spinal fusion with or without instrumentation often requires the use of bone
      graft. Bone graft may be autogenous or exogenous. There are various forms of bone
      graft which may be acquired from numerous sites. Knowledge of fusion biology is
      imperative for understanding the benefits and limitations of these grafts.
      Equally as important is the knowledge of outcome measures, management of donor
      site morbidity, and potential reconstruction. This review details the methods of
      obtaining bone graft and details the properties of each, as well as discusses
      observed outcomes, donor-site morbidities, and reconstruction techniques. 

PMID- 25845672
TI  - Compliance of blood donation apps with mobile OS usability guidelines.
AB  - The aim of this paper is to employ the guidelines of Android, iOS, Blackberry and
      Windows Phone to analyze the usability compliance of free blood donation (BD)
      apps. An analysis process based on a systematic review protocol is used to select
      free BD apps. An assessment is conducted using a questionnaire composed of 13
      questions concerning the compliance of free BD apps with Android, Blackberry, iOS
      and Windows Phone usability guidelines. A total of 133 free BD apps have been
      selected from the 188 BD apps identified. Around 63% of the free BD apps selected
      have a good compliance with mobile OS usability recommendations. Around 72% of
      Android, 57% of Windows Phone, 33% of iOS and 33% of Blackberry BD apps have a
      high usability score. The aspect of BD app behavior should be improved along with
      some style components: the use of pictures to explain ideas and the adaptation of
      the app to both horizontal and vertical orientations. Structure patterns should
      also be used to improve the structure aspect of a BD app. Usability is a quality
      aspect that should be improved in current BD apps. Our study provides smartphone
      users with a list of usable free BD apps and BD app developers with
      recommendations.

PMID- 25845673
TI  - The Inflammatory Hypothesis of Atrial Fibrillation: Diagnostic Marker,
      Therapeutic Target, or Innocent Bystander?

PMID- 25845674
TI  - Determined to Die! Ability to Act Following Multiple Self-inflicted Gunshot
      Wounds to the Head. The Cook County Office of Medical Examiner Experience (2005
      2012) and Review of Literature.
AB  - Cases of multiple (considered 2+) self-inflicted gunshot wounds are a rarity and
      require careful examination of the scene of occurrence; thorough consideration of
      the decedent's psychiatric, medical, and social histories; and accurate
      postmortem documentation of the gunshot wounds. We present a series of four cases
      of multiple self-inflicted gunshot wounds to the head from the Cook County
      Medical Examiner's Office between 2005 and 2012 including the first case report
      of suicide involving eight gunshot wounds to the head. In addition, a review of
      the literature concerning multiple self-inflicted gunshot wounds to the head is
      performed. The majority of reported cases document two gunshot entrance wound
      defects. Temporal regions are the most common affected regions (especially the
      right and left temples). Determining the capability to act following a gunshot
      wound to the head is necessary in crime scene reconstruction and in
      differentiation between homicide and suicide. 

PMID- 25845675
TI  - The different role of sex hormones on female cardiovascular physiology and
      function: not only oestrogens.
AB  - Human response to different physiologic stimuli and cardiovascular (CV)
      adaptation to various pathologies seem to be gender specific. Sex-steroid
      hormones have been postulated as the major contributors towards these sex-related
      differences. This review will discuss current evidence on gender differences in
      CV function and remodelling, and will present the different role of the principal
      sex-steroid hormones on female heart. Starting from a review of sex hormones
      synthesis, receptors and CV signalling, we will summarize the current knowledge
      concerning the role of sex hormones on the regulation of our daily activities
      throughout the life, via the modulation of autonomic nervous system, excitation
      contraction coupling pathway and ion channels activity. Many unresolved questions
      remain even if oestrogen effects on myocardial remodelling and function have been
      extensively studied. So this work will focus attention also on the controversial
      and complex relationship existing between androgens, progesterone and female
      heart. 

PMID- 25845676
TI  - Targeted metabolic profiling of wounds in diabetic and nondiabetic mice.
AB  - While cellular metabolism is known to regulate a number of key biological
      processes such as cell growth and proliferation, its role in wound healing is
      unknown. We hypothesized that cutaneous injury would induce significant metabolic
      changes and that the impaired wound healing seen in diabetes would be associated
      with a dysfunctional metabolic response to injury. We used a targeted
      metabolomics approach to characterize the metabolic profile of uninjured skin and
      full-thickness wounds at day 7 postinjury in nondiabetic (db/-) and diabetic
      (db/db) mice. By liquid chromatography mass spectrometry, we identified 129
      metabolites among all tissue samples. Principal component analysis demonstrated
      that uninjured skin and wounds have distinct metabolic profiles and that diabetes
      alters the metabolic profile of both uninjured skin and wounds. Examining
      individual metabolites, we identified 62 with a significantly altered response to
      injury in the diabetic mice, with many of these, including glycine, kynurenate,
      and OH-phenylpyruvate, implicated in wound healing for the first time. Thus, we
      report the first comprehensive analysis of wound metabolic profiles, and our
      results highlight the potential for metabolomics to identify novel biomarkers and
      therapeutic targets for improved wound healing outcomes. 

PMID- 25845677
TI  - Development of the affinity materials for phosphorylated proteins/peptides
      enrichment in phosphoproteomics analysis.
AB  - Reversible protein phosphorylation is a key event in numerous biological
      processes. Mass spectrometry (MS) is the most powerful analysis tool in modern
      phosphoproteomics. However, the direct MS analysis of phosphorylated
      proteins/peptides is still a big challenge because of the low abundance and
      insufficient ionization of phosphorylated proteins/peptides as well as the
      suppression effects of nontargets. Enrichment of phosphorylated proteins/peptides
      by affinity materials from complex biosamples is the most widely used strategy to
      enhance the MS detection. The demand of efficiently enriching phosphorylated
      proteins/peptides has spawned diverse affinity materials based on different
      enrichment principles (e.g., electronic attraction, chelating). In this review,
      we summarize the recent development of various affinity materials for
      phosphorylated proteins/peptides enrichment. We will highlight the design and
      fabrication of these affinity materials, discuss the enrichment mechanisms
      involved in different affinity materials, and suggest the future challenges and
      research directions in this field. 

PMID- 25845679
TI  - The effects of slope and branch structure on the locomotion of a specialized
      arboreal colubrid snake (Boiga irregularis).
AB  - The surfaces in arboreal habitats have variable diameters, slopes, and branching
      structure that pose functional challenges for animal locomotion. Nevertheless,
      many lineages of snakes have independently evolved arboreality. We tested the
      effects of arboreal habitat structure on the locomotion of a highly arboreal
      species, the brown tree snake (Boiga irregularis), moving on seven diameters (0.6
      21 cm) of cylinders oriented at three slopes (0 degrees , 45 degrees , 90 degrees
      ) and with or without pegs. Intermediate diameters of horizontal cylinders
      maximized speed, and some of the large-diameter cylinders without pegs were
      impassable when they were inclined. With increased slope the snakes were slower,
      and they changed from using lateral undulation with sliding contact and balancing
      to concertina locomotion with periodic static gripping. The presence of pegs
      increased the speeds of the brown tree snakes and resulted in them only using
      lateral undulation. Surface diameter, slope, and the occurrence of pegs also had
      widespread significant effects on the kinematics of the brown tree snakes.
      Overall, compared to anatomically less specialized corn snakes, brown tree snakes
      use more lateral undulation, are usually much faster, and are able to move on a
      wider variety of surfaces. Unlike some of the trade-offs found previously between
      two less specialized species of snakes with different stoutness when they used
      modes of arboreal locomotion that involved either balancing or gripping, the
      slender-bodied brown tree snakes excel at both. Hence, this species may not only
      be a "jack of all trades" but also a master of many.

PMID- 25845678
TI  - Falls in ambulatory non-demented patients with Parkinson's disease.
AB  - This study aimed at determining the prevalence of falling in PD patients, to
      assess generic and disease-specific clinical and pharmacological factors,
      relationship with health-related quality of life (HR-QoL) and changes in falls
      from OFF to ON in patients with motor fluctuations. Six-hundred and eighty-three
      PD patients of the COPARK survey were evaluated (11 had missing data and were
      excluded from the analysis). Patients with falls were identified as those with a
      UPDRS Item 13 >= 1 in the ON condition. All patients were assessed in a
      standardized manner [demographics, treatments, Unified PD Rating Scale (UPDRS),
      Hospital Anxiety and Depression Scale, Pittsburg questionnaire and HR-QoL scales
      (SF36, PDQ39)]. Falling was reported by 108/672 (16%) PD patients during the ON
      state and prevalence increased according to PD severity, from 5% in Hoehn and
      Yahr stage 1-60% in stage 4. Falling was significantly related to lower HR-QoL.
      Falling correlated with (1) generic factors such as female gender, age at the end
      of academic studies and diuretics consumption, (2) motor PD-specific factors
      including disease severity, frozen gait, difficulties when arising from a chair,
      dyskinesia and higher levodopa daily equivalent dose and (3) non-motor PD
      specific factors such as orthostatic hypotension and hallucinations. Falling was
      more frequent in OFF than in ON in 48/74 (64%) patients with motor fluctuations
      and remained unchanged in 27 patients (36%). In summary, falling affected a
      significant proportion of PD patients, especially in advanced stages. It was
      associated with a variety of generic and PD-specific factors and was related to
      reduced HR-QoL.

PMID- 25845680
TI  - Synbiotics-supplemented amino acid-based formula supports adequate growth in
      cow's milk allergic infants.
AB  - BACKGROUND: Children with cow's milk allergy (CMA) are at risk for inadequate
      nutritional intake and growth. Dietary management of CMA, therefore, requires
      diets that are not only hypoallergenic but also support adequate growth in this
      population. This study assessed growth of CMA infants when using a new amino acid
      based formula (AAF) with prebiotics and probiotics (synbiotics) and evaluated its
      safety in the intended population. METHODS: In a prospective, randomized, double
      blind controlled study, full-term infants with diagnosed CMA received either an
      AAF (control; n = 56) or AAF with synbiotics (oligofructose, long-chain inulin,
      acidic oligosaccharides, Bifidobacterium breve M-16V) (test; n = 54) for 16 wk.
      Primary outcome was growth, measured as weight, length and head circumference.
      Secondary outcomes included allergic symptoms and stool characteristics. RESULTS:
      Average age (+/-SD) of infants at inclusion was 4.5 +/- 2.4 months. Both formulas
      equally supported growth according to WHO 2006 growth charts and resulted in
      similar increases of weight, length and head circumference. At week 16,
      differences (90% CI) in Z-scores (test-control) were as follows: weight 0.147 (
      0.10; 0.39, p = 0.32), length -0.299 (-0.69; 0.09, p = 0.21) and head
      circumference 0.152 (-0.15; 0.45, p = 0.40). Weight-for-age and length-for-age Z
      scores were not significantly different between the test and control groups. Both
      formulas were well tolerated and reduced allergic symptoms; the number of adverse
      events was not different between the groups. CONCLUSIONS: This is the first study
      that shows that an AAF with a specific synbiotic blend, suitable for CMA infants,
      supports normal growth and growth similar to the AAF without synbiotics. This
      clinical trial is registered as NCT00664768.

PMID- 25845681
TI  - Icariin regulates the proliferation and apoptosis of human ovarian cancer cells
      through microRNA-21 by targeting PTEN, RECK and Bcl-2.
AB  - Icariin is the main active ingredient found in the traditional Chinese medicinal
      plant Epimedium, and exhibits various pharmacological effects such as enhanced
      immune function, anticancer activity, improved cardiovascular function and
      endocrine adjustment. However, the effect of icariin on ovarian cancer and the
      related mechanism have never been investigated. In the present study, we aimed to
      verify whether icariin inhibits the proliferation and increases the apoptosis of
      human ovarian cancer cells, and its molecular mechanism in order to establish an
      association and identify potential therapeutic targets. In the present study,
      ovarian cancer A2780 cells were treated with various concentrations of icariin,
      and the cell viability was evaluated by 3,3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay. Flow cytometry and caspase-3
      colorimetric assay were performed to observe apoptotic changes in the A2780
      cells. qPCR analysis was used to analyze miR-21 expression in the A2780 cells.
      Western blot analysis was used to assess PTEN, RECK and Bcl-2 protein expression.
      Transfection of microRNA-21 (miR-21) and anti-miR-21 was used to investigate
      expression of its target genes associated with cell proliferation and apoptosis.
      Icariin concomitantly suppressed cell proliferation, accelerated apoptosis and
      increased caspase-3 activity in the A2780 cells. In the ovarian cancer A2780
      cells, icariin substantially decreased the miR-21 expression level, increased
      PTEN and RECK protein expression levels and decreased the Bcl-2 protein
      expression level. Notably, miR-21 regulated the potential anticancer effects of
      icariin on cell proliferation and apoptosis by targeting PTEN, RECK and Bcl-2 in
      the ovarian cancer A2780 cells. Our results demonstrated that icariin is an
      excellent candidate antitumor agent which exhibits an anticancer curative effect
      on ovarian cancer cells. miR-21 and its target genes may play a vital role in the
      molecular mechanism of the anticancer effects of icariin. 

PMID- 25845682
TI  - Half a century of the Burgenstock Conference: a pilgrim's tale.
AB  - "...? The Burgenstock program always allows for important scientific discussion.
      It is clear that this meeting is valuable for the scientific community as it is
      on one hand important for its deep historical significance, and on the other hand
      crucial for what it preserves of great scientific tradition for future
      generations. Every meeting contained a lesson learned and further brought
      together the family of stereochemists ...?" Read more in the Editorial by Jay S.
      Siegel. 

PMID- 25845683
TI  - Obstructive sleep apnea: how much is too much?

PMID- 25845684
TI  - On the role of sleep intensity in a model of sleep regulation.

PMID- 25845685
TI  - Shooting STAR: Caution in Interpreting Long-Term Cost Effectiveness from a Short
      Term Case-Series.

PMID- 25845686
TI  - The Multidimensional Aspects of Sleep Spindles and Their Relationship to Word
      Pair Memory Consolidation.
AB  - STUDY OBJECTIVES: Several studies proposed a link between sleep spindles and
      sleep dependent memory consolidation in declarative learning tasks. In addition
      to these state-like aspects of sleep spindles, they have also trait-like
      characteristics, i.e., were related to general cognitive performance, an
      important distinction that has often been neglected in correlative studies.
      Furthermore, from the multitude of different sleep spindle measures, often just
      one specific aspect was analyzed. Thus, we aimed at taking multidimensional
      aspects of sleep spindles into account when exploring their relationship to word
      pair memory consolidation. DESIGN: Each subject underwent 2 study nights with all
      night high-density electroencephalographic (EEG) recordings. Sleep spindles were
      automatically detected in all EEG channels. Subjects were trained and tested on a
      word-pair learning task in the evening, and retested in the morning to assess
      sleep related memory consolidation (overnight retention). Trait-like aspects
      refer to the mean of both nights and state-like aspects were calculated as the
      difference between night 1 and night 2. SETTING: Sleep laboratory. PARTICIPANTS:
      Twenty healthy male subjects (age: 23.3 +/- 2.1 y). MEASUREMENTS AND RESULTS:
      Overnight retention was negatively correlated with trait-like aspects of fast
      sleep spindle density and positively with slow spindle density on a global level.
      In contrast, state-like aspects were observed for integrated slow spindle
      activity, which was positively related to the differences in overnight retention
      in specific regions. CONCLUSION: Our results demonstrate the importance of a
      multidimensional approach when investigating the relationship between sleep
      spindles and memory consolidation and thereby provide a more complete picture
      explaining divergent findings in the literature.

PMID- 25845687
TI  - Increased Carbonic Anhydrase Activity is Associated with Sleep Apnea Severity and
      Related Hypoxemia.
AB  - STUDY OBJECTIVES: The catalytic function of the enzyme carbonic anhydrase (CA)
      plays a fundamental role in carbon dioxide (CO2), proton (H(+)), and bicarbonate
      (HCO3(-)) homeostasis. Hypoxia and tissue acidosis have been proposed to increase
      physiological CA activity in various compartments of the body. We hypothesized
      that CA activity in blood is upregulated in patients with obstructive sleep apnea
      (OSA). DESIGN: Cross-sectional analysis of a sleep clinic cohort. SETTINGS: Sleep
      laboratory at a university hospital. PARTICIPANTS: Seventy referred patients with
      suspected OSA (48 males, age 54 +/- 13 y, apnea-hypopnea index (AHI) median
      [interquartile range] 21 [8-41] n/h). INTERVENTIONS: N/A. MEASUREMENTS AND
      RESULTS: In-laboratory cardiorespiratory polygraphy was used to assess OSA. CA
      activity was determined by an in vitro assay that quantifies the pH change
      reflecting the conversion of CO2 and H2O to HCO3(-) and H(+). CA activity was
      positively associated with AHI and 4% oxygen desaturation index (ODI4) (Spearman
      correlation r = 0.44 and 0.47, both P < 0.001). The associations (CA activity
      versus logAHI and CA versus logODI4) were independent of sex, age, body mass
      index, presleep oxygen saturation, nocturnal oxygen saturation, hypertension
      status, and use of diuretic medication in two generalized linear models (P =
      0.007 and 0.011, respectively). Sitting diastolic blood pressure was associated
      with CA activity after adjustment of sex, age, body mass index, mean oxygen
      saturation, and AHI (P = 0.046). CONCLUSIONS: Carbonic anhydrase (CA) activity
      increased with apnea-hypopnea index and related nocturnal hypoxemia measures in
      patients with obstructive sleep apnea (OSA). Altered CA activity may constitute a
      component that modulates respiratory control and hemodynamic regulation in
      patients with OSA.

PMID- 25845688
TI  - African Genetic Ancestry is Associated with Sleep Depth in Older African
      Americans.
AB  - STUDY OBJECTIVES: The mechanisms that underlie differences in sleep
      characteristics between European Americans (EA) and African Americans (AA) are
      not fully known. Although social and psychological processes that differ by race
      are possible mediators, the substantial heritability of sleep characteristics
      also suggests genetic underpinnings of race differences. We hypothesized that
      racial differences in sleep phenotypes would show an association with objectively
      measured individual genetic ancestry in AAs. DESIGN: Cross sectional. SETTING:
      Community-based study. PARTICIPANTS: Seventy AA adults (mean age 59.5 +/- 6.7 y;
      62% female) and 101 EAs (mean age 60.5 +/- 7 y, 39% female). MEASUREMENTS AND
      RESULTS: Multivariate tests were used to compare the Pittsburgh Sleep Quality
      Index (PSQI) and in-home polysomnographic measures of sleep duration, sleep
      efficiency, apnea-hypopnea index (AHI), and indices of sleep depth including
      percent visually scored slow wave sleep (SWS) and delta EEG power of EAs and AAs.
      Sleep duration, efficiency, and sleep depth differed significantly by race.
      Individual % African ancestry (%AF) was measured in AA subjects using a panel of
      1698 ancestry informative genetic markers and ranged from 10% to 88% (mean 67%).
      Hierarchical linear regression showed that higher %AF was associated with lower
      percent SWS in AAs (beta (standard error) = -4.6 (1.5); P = 0.002), and explained
      11% of the variation in SWS after covariate adjustment. A similar association was
      observed for delta power. No association was observed for sleep duration and
      efficiency. CONCLUSION: African genetic ancestry is associated with indices of
      sleep depth in African Americans. Such an association suggests that part of the
      racial differences in slow-wave sleep may have genetic underpinnings.

PMID- 25845689
TI  - Increased Automaticity and Altered Temporal Preparation Following Sleep
      Deprivation.
AB  - STUDY OBJECTIVES: Temporal expectation enables us to focus limited processing
      resources, thereby optimizing perceptual and motor processing for critical
      upcoming events. We investigated the effects of total sleep deprivation (TSD) on
      temporal expectation by evaluating the foreperiod and sequential effects during a
      psychomotor vigilance task (PVT). We also examined how these two measures were
      modulated by vulnerability to TSD. DESIGN: Three 10-min visual PVT sessions using
      uniformly distributed foreperiods were conducted in the wake-maintenance zone the
      evening before sleep deprivation (ESD) and three more in the morning following
      approximately 22 h of TSD. TSD vulnerable and nonvulnerable groups were
      determined by a tertile split of participants based on the change in the number
      of behavioral lapses recorded during ESD and TSD. A subset of participants
      performed six additional 10-min modified auditory PVTs with exponentially
      distributed foreperiods during rested wakefulness (RW) and TSD to test the effect
      of temporal distribution on foreperiod and sequential effects. SETTING: Sleep
      laboratory. PARTICIPANTS: There were 172 young healthy participants (90 males)
      with regular sleep patterns. Nineteen of these participants performed the
      modified auditory PVT. MEASUREMENTS AND RESULTS: Despite behavioral lapses and
      slower response times, sleep deprived participants could still perceive the
      conditional probability of temporal events and modify their level of preparation
      accordingly. Both foreperiod and sequential effects were magnified following
      sleep deprivation in vulnerable individuals. Only the foreperiod effect increased
      in nonvulnerable individuals. CONCLUSIONS: The preservation of foreperiod and
      sequential effects suggests that implicit time perception and temporal
      preparedness are intact during total sleep deprivation. Individuals appear to
      reallocate their depleted preparatory resources to more probable event timings in
      ongoing trials, whereas vulnerable participants also rely more on automatic
      processes.

PMID- 25845690
TI  - Nocturnal Sleep Dynamics Identify Narcolepsy Type 1.
AB  - STUDY OBJECTIVES: To evaluate the reliability of nocturnal sleep dynamics in the
      differential diagnosis of central disorders of hypersomnolence. DESIGN: Cross
      sectional. SETTING: Sleep laboratory. PATIENTS: One hundred seventy-five patients
      with hypocretin-deficient narcolepsy type 1 (NT1, n = 79), narcolepsy type 2
      (NT2, n = 22), idiopathic hypersomnia (IH, n = 22), and "subjective"
      hypersomnolence (sHS, n = 52). INTERVENTIONS: None. METHODS: Polysomnographic
      (PSG) work-up included 48 h of continuous PSG recording. From nocturnal PSG
      conventional sleep macrostructure, occurrence of sleep onset rapid eye movement
      period (SOREMP), sleep stages distribution, and sleep stage transitions were
      calculated. Patient groups were compared, and receiver operating characteristic
      (ROC) curve analysis was used to test the diagnostic utility of nocturnal PSG
      data to identify NT1. RESULTS: Sleep macrostructure was substantially stable in
      the 2 nights of each diagnostic group. NT1 and NT2 patients had lower latency to
      rapid eye movement (REM) sleep, and NT1 patients showed the highest number of
      awakenings, sleep stage transitions, and more time spent in N1 sleep, as well as
      most SOREMPs at daytime PSG and at multiple sleep latency test (MSLT) than all
      other groups. ROC curve analysis showed that nocturnal SOREMP (area under the
      curve of 0.724 +/- 0.041, P < 0.0001), percent of total sleep time spent in N1
      (0.896 +/- 0.023, P < 0.0001), and the wakefulness-sleep transition index (0.796
      +/- 0.034, P < 0.0001) had a good sensitivity and specificity profile to identify
      NT1 sleep, especially when used in combination (0.903 +/- 0.023, P < 0.0001),
      similarly to SOREMP number at continuous daytime PSG (0.899 +/- 0.026, P <
      0.0001) and at MSLT (0.956 +/- 0.015, P < 0.0001). CONCLUSIONS: Sleep
      macrostructure (i.e. SOREMP, N1 timing) including stage transitions reliably
      identifies hypocretin-deficient narcolepsy type 1 among central disorders of
      hypersomnolence.

PMID- 25845691
TI  - Trajectories of Sleep Quality and Associations with Mood during the Perinatal
      Period.
AB  - OBJECTIVE: The aim of this study was to investigate trajectories of sleep quality
      and associations with mood in the perinatal period. Although it is commonly
      accepted that subjective sleep quality declines during pregnancy and the
      transition to parenthood, some women may follow qualitatively distinct
      trajectories. DESIGN, SETTING, AND PARTICIPANTS: Sleep quality was assessed by
      the Pittsburgh Sleep Quality Index (PSQI). Data were collected from 293 women at
      four time points: during early pregnancy, at Time 1 (T1; < 22 w gestational age
      [GA]; late pregnancy, at Time 2 (T2; 32 w GA); during the postnatal period at
      Time 3 (T3; 3 mo postpartum); and Time 4 (T4; 6 mo postpartum). A group-based
      semiparametric mixture model was used to estimate patterns of sleep quality
      throughout the perinatal period. RESULTS: Four trajectory groups were identified,
      including patterns defined by high sleep quality throughout (21.5%), mild
      decrease in sleep quality (59.5%), significant decrease in sleep quality (12.3%)
      and a group with poor sleep quality throughout (6.7%). Women who had the worst
      sleep quality at Time 1 and those who experienced significant increases in sleep
      problems throughout pregnancy were also the groups who reported the highest
      levels of anxiety and depressive symptoms in early pregnancy and the lowest
      levels of social support. After controlling for covariates, the groups with worst
      subjective sleep quality during pregnancy were also the most likely to experience
      high symptoms of depression in the postpartum period. CONCLUSIONS: Most of the
      women in our sample reported mild sleep disturbances through the perinatal
      period. A subgroup of women reported a significant decline in sleep quality from
      early to late pregnancy and another reported poor subjective sleep quality
      throughout pregnancy; these groups had the greatest risk of experiencing high
      symptoms of depression in the postpartum period.

PMID- 25845692
TI  - The Role of the Serotonergic System in REM Sleep Behavior Disorder.
AB  - STUDY OBJECTIVES: REM sleep behavior disorder (RBD) can be induced by
      antidepressants, especially serotonin reuptake inhibitors (SSRI), thus a role of
      the serotonergic system in the pathogenesis of RBD has been proposed. However,
      the serotonergic system integrity in idiopathic RBD (iRBD) is still unknown. We
      aimed to study brain stem serotonergic system integrity, by means of (123)I-FP
      CIT-SPECT, in a group of iRBD patients as compared to normal subjects. DESIGN:
      Single-center, prospective observational study. SETTING: University hospital.
      PATIENTS OR PARTICIPANTS: Twenty iRBD outpatients and 23 age-matched normal
      controls. MEASUREMENTS AND RESULTS: The diagnosis of RBD was determined
      clinically and confirmed by means of overnight, laboratory-based video
      polysomnography. Both iRBD patients and normal subjects underwent (123)I-FP-CIT
      SPECT as a marker of dopamine transporter (DAT) at basal ganglia level and of
      serotonin transporter (SERT) at brainstem and thalamus levels. (123)I-FP-CIT
      SPECT images were analyzed and compared between iRBD patients and controls by
      means of both region of interest analysis at basal ganglia, midbrain, pons and
      thalamus levels, and voxel-based analysis, taking into account age and the use of
      SSRI as confounding factors. No difference in (123)I-FP-CIT-SPECT specific to
      nondisplaceable binding ratios (SBR) values was found between iRBD and normal
      subjects at brainstem and thalamus levels while iRBD patients showed lower SBR
      values in all basal ganglia nuclei (P < 0.0001) compared to controls.
      CONCLUSIONS: These results suggest that the serotonergic system is not directly
      involved in RBD pathogenesis while confirming nigro-striatal dopaminergic
      deafferentation in iRBD.

PMID- 25845693
TI  - Poor Sleep Quality and Associated Inflammation Predict Preterm Birth: Heightened
      Risk among African Americans.
AB  - STUDY OBJECTIVES: Poor sleep promotes inflammation. In turn, inflammation is a
      causal mechanism in term as well as preterm parturition. In the United States, a
      persistent racial disparity in preterm birth exists, with African Americans
      showing ~1.5 times greater risk. This study examined associations among sleep
      quality, serum proinflammatory cytokines, and length of gestation in a racially
      diverse sample of 138 pregnant women. DESIGN: Observational. MEASUREMENTS: Women
      completed the Pittsburgh Sleep Quality Index (PSQI) and other psychosocial and
      behavioral measures during midpregnancy. Serum levels of interleukin (IL)-6, IL
      8, IL-1beta, and tumor necrosis factor (TNF)-alpha were determined by high
      sensitivity assays. Birth outcomes were determined via medical record review.
      RESULTS: Among African American women (n = 79), shorter gestation was predicted
      by poorer overall sleep (rs = -0.35, P = 0.002) as well the following PSQI
      subscales: subjective sleep quality (rs = -0.34, P = 0.002), sleep latency (rs = 
      0.27, P = 0.02), and sleep efficiency (rs = -0.27, P = 0.02). African American
      women with poor sleep quality (PSQI > 5) had 10.2 times the odds of preterm birth
      compared to those with good sleep quality. In contrast, among European American
      women (n = 53), gestational length was not significantly predicted by sleep
      quality (Ps > 0.12). Bootstrapping analyses showed that, among African Americans,
      IL-8 significantly mediated the association between sleep quality and length of
      gestation (indirect effect estimate -0.029; 95% confidence interval -0.06, 
      0.002). CONCLUSIONS: The data provide novel evidence that African American women
      exhibit greater inflammation in response to sleep disturbance than European
      American women and these effects correspond with length of gestation. Racial
      differences in susceptibility to sleep induced immune dysregulation may
      contribute to marked racial disparities in preterm birth.

PMID- 25845694
TI  - Sleep Disordered Breathing in Four Resource-Limited Settings in Peru: Prevalence,
      Risk Factors, and Association with Chronic Diseases.
AB  - STUDY OBJECTIVES: Sleep disordered breathing (SDB) is a highly prevalent
      condition in high-income countries, with major consequences for cardiopulmonary
      health, public safety, healthcare utilization, and mortality. However, its
      prevalence and effect in low- and middle-income countries are less well known. We
      sought to determine the prevalence, risk factors, and comorbidities of SDB
      symptoms in four resource-limited settings. DESIGN: Cross-sectional analysis of
      the CRONICAS Cohort, a population-based age- and sex-stratified sample. SETTING:
      Four resource-limited settings in Peru varying in altitude, urbanization, and air
      pollution. PARTICIPANTS: There were 2,682 adults aged 35 to 92 y. MEASUREMENTS
      AND RESULTS: Self-reported SDB symptoms (habitual snoring, observed apneas,
      Epworth Sleepiness Scale), sociodemographics, medical history, anthropometrics,
      spirometry, blood biomarkers were reported. We found a high prevalence of
      habitual snoring (30.2%, 95% confidence interval [CI] 28.5-32.0%), observed
      apneas (20.9%, 95% CI 19.4-22.5%) and excessive daytime sleepiness (18.6%, 95% CI
      17.1-20.1%). SDB symptoms varied across sites; prevalence and adjusted odds for
      habitual snoring were greatest at sea level, whereas those for observed apneas
      were greatest at high altitude. In multivariable analysis, habitual snoring was
      associated with older age, male sex, body mass index (BMI), and higher
      socioeconomic status; observed apneas were associated with BMI; and excessive
      daytime sleepiness was associated with older age, female sex, and medium
      socioeconomic status. Adjusted odds of cardiovascular disease, depression, and
      hypertension and total chronic disease burden increased progressively with the
      number of SDB symptoms. A threefold increase in the odds of having an additional
      chronic comorbid disease (adjusted odds ratio 3.57, 95% CI 2.18-5.84) was
      observed in those with all three versus no SDB symptoms. CONCLUSIONS: Sleep
      disordered breathing symptoms were highly prevalent, varied widely across four
      resource-limited settings in Peru, and exhibited strong independent associations
      with chronic diseases.

PMID- 25845695
TI  - Cacna1c (Cav1.2) Modulates Electroencephalographic Rhythm and Rapid Eye Movement
      Sleep Recovery.
AB  - STUDY OBJECTIVES: The CACNA1C gene encodes the alpha 1C (alpha1C) subunit of the
      Cav1.2 voltage-dependent L-type calcium channel (LTCC). Some of the other voltage
      dependent calcium channels, e.g., P-/Q-type, Cav2.1; N-type, Cav2.2; E-/R-type,
      Cav2.3; and T-type, Cav3.3 have been implicated in sleep modulation. However, the
      contribution of LTCCs to sleep remains largely unknown. Based on recent genome
      wide association studies, CACNA1C emerged as one of potential candidate genes
      associated with both sleep and psychiatric disorders. Indeed, most patients with
      mental illnesses have sleep problems and vice versa. DESIGN: To investigate an
      impact of Cav1.2 on sleep-wake behavior and electroencephalogram (EEG) activity,
      polysomnography was performed in heterozygous Cacna1c (HET) knockout mice and
      their wild-type (WT) littermates under baseline and challenging conditions (acute
      sleep deprivation and restraint stress). MEASUREMENTS AND RESULTS: HET mice
      displayed significantly lower EEG spectral power than WT mice across high
      frequency ranges (beta to gamma) during wake and rapid eye movement (REM) sleep.
      Although HET mice spent slightly more time asleep in the dark period, daily
      amounts of sleep did not differ between the two genotypes. However, recovery
      sleep after exposure to both types of challenging stress conditions differed
      markedly; HET mice exhibited reduced REM sleep recovery responses compared to WT
      mice. CONCLUSIONS: These results suggest the involvement of Cacna1c (Cav1.2) in
      fast electroencephalogram oscillations and REM sleep regulatory processes. Lower
      spectral gamma activity, slightly increased sleep demands, and altered REM sleep
      responses found in heterozygous Cacna1c knockout mice may rather resemble a sleep
      phenotype observed in schizophrenia patients.

PMID- 25845697
TI  - Reproducibility of a Standardized Actigraphy Scoring Algorithm for Sleep in a US
      Hispanic/Latino Population.
AB  - STUDY OBJECTIVES: While actigraphy is considered objective, the process of
      setting rest intervals to calculate sleep variables is subjective. We sought to
      evaluate the reproducibility of actigraphy-derived measures of sleep using a
      standardized algorithm for setting rest intervals. DESIGN: Observational study.
      SETTING: Community-based. PARTICIPANTS: A random sample of 50 adults aged 18-64
      years free of severe sleep apnea participating in the Sueno sleep ancillary study
      to the Hispanic Community Health Study/Study of Latinos. INTERVENTIONS: N/A.
      MEASUREMENTS AND RESULTS: Participants underwent 7 days of continuous wrist
      actigraphy and completed daily sleep diaries. Studies were scored twice by each
      of two scorers. Rest intervals were set using a standardized hierarchical
      approach based on event marker, diary, light, and activity data. Sleep/wake
      status was then determined for each 30-sec epoch using a validated algorithm, and
      this was used to generate 11 variables: mean nightly sleep duration, nap
      duration, 24-h sleep duration, sleep latency, sleep maintenance efficiency, sleep
      fragmentation index, sleep onset time, sleep offset time, sleep midpoint time,
      standard deviation of sleep duration, and standard deviation of sleep midpoint.
      Intra-scorer intraclass correlation coefficients (ICCs) were high, ranging from
      0.911 to 0.995 across all 11 variables. Similarly, inter-scorer ICCs were high,
      also ranging from 0.911 to 0.995, and mean inter-scorer differences were small.
      Bland-Altman plots did not reveal any systematic disagreement in scoring.
      CONCLUSIONS: With use of a standardized algorithm to set rest intervals, scoring
      of actigraphy for the purpose of generating a wide array of sleep variables is
      highly reproducible.

PMID- 25845696
TI  - Promotion of Wakefulness and Energy Expenditure by Orexin-A in the Ventrolateral
      Preoptic Area.
AB  - STUDY OBJECTIVES: The ventrolateral preoptic area (VLPO) and the
      orexin/hypocretin neuronal system are key regulators of sleep onset, transitions
      between vigilance states, and energy homeostasis. Reciprocal projections exist
      between the VLPO and orexin/hypocretin neurons. Although the importance of the
      VLPO to sleep regulation is clear, it is unknown whether VLPO neurons are
      involved in energy balance. The purpose of these studies was to determine if the
      VLPO is a site of action for orexin-A, and which orexin receptor subtype(s) would
      mediate these effects of orexin-A. We hypothesized that orexin-A in the VLPO
      modulates behaviors (sleep and wakefulness, feeding, spontaneous physical
      activity [SPA]) to increase energy expenditure. DESIGN AND MEASUREMENTS: Sleep,
      wakefulness, SPA, feeding, and energy expenditure were determined after orexin-A
      microinjection in the VLPO of male Sprague-Dawley rats with unilateral cannulae
      targeting the VLPO. We also tested whether pretreatment with a dual orexin
      receptor antagonist (DORA, TCS-1102) or an OX2R antagonist (JNJ-10397049) blocked
      the effects of orexin-A on the sleep/wake cycle or SPA, respectively. RESULTS:
      Orexin-A injected into the VLPO significantly increased wakefulness, SPA, and
      energy expenditure (SPA-induced and total) and reduced NREM sleep and REM sleep
      with no effect on food intake. Pretreatment with DORA blocked the increase in
      wakefulness and the reduction in NREM sleep elicited by orexin-A, and the OX2R
      antagonist reduced SPA stimulated by orexin-A. CONCLUSIONS: These data show the
      ventrolateral preoptic area is a site of action for orexin-A, which may promote
      negative energy balance by modulating sleep/wakefulness and stimulating
      spontaneous physical activity and energy expenditure.

PMID- 25845698
TI  - Polysomnographic Findings and Clinical Correlates in Huntington Disease: A Cross
      Sectional Cohort Study.
AB  - STUDY OBJECTIVES: To evaluate the sleep pattern and the motor activity during
      sleep in a cohort of patients affected by Huntington disease (HD). DESIGN: Cross
      sectional cohort study. SETTING: Sleep laboratory. PATIENTS: Thirty HD patients,
      16 women and 14 men (mean age 57.3 +/- 12.2 y); 30 matched healthy controls (mean
      age 56.5 +/- 11.8 y). INTERVENTIONS: Subjective sleep evaluation: Epworth
      Sleepiness Scale (ESS); Berlin's Questionnaire, interview for restless legs
      syndrome (RLS), questionnaire for REM sleep behavior disorder (RBD). Clinical
      evaluation: disease duration, clinical severity (unified Huntington disease motor
      rating scale [UHDMRS]), genetic tests. Laboratory-based full-night attended video
      polysomnography (V-PSG). MEASUREMENTS AND RESULTS: The duration of the disease
      was 9.4 +/- 4.4 y, UHMDRS score was 55.5 +/- 23.4, CAG repeats were 44.3 +/- 4.1.
      Body mass index was 21.9 +/- 4.0 kg/m(2). No patients or caregivers reported poor
      sleep quality. Two patients reported symptoms of RLS. Eight patients had an ESS
      score >= 9. Eight patients had high risk of obstructive sleep apnea. At the RBD
      questionnaire, two patients had a pathological score. HD patients, compared to
      controls, showed shorter sleep, reduced sleep efficiency index, and increased
      arousals and awakenings. Four patients presented with sleep disordered breathing
      (SDB). Periodic limb movements (PLMs) during wake and sleep were observed in all
      patients. No episode of RBD was observed in the V-PSG recordings, and no patients
      showed rapid eye movement (REM) sleep without atonia. The disease duration
      correlated with ESS score (P < 0.02). UHMDRS correlated positively with the ESS
      score (P < 0.005), and negatively with the percentage of REM sleep. CONCLUSIONS:
      Patients with Huntington disease showed a severe sleep disruption and a high
      prevalence of periodic limb movements, but no evidence of sleep disordered
      breathing or REM sleep behavior disorder.

PMID- 25845699
TI  - Identification of NF-kappaB inhibitors in Qishenyiqi dropping pills for
      myocardial infarction treatment based on bioactivity-integrated UPLC-Q/TOF MS.
AB  - Qishenyiqi dropping pills (QSYQ) are a type of standardized cardiovascular
      multiherb medicine for the treatment of myocardial infarction (MI). Knowledge
      concerning the systemic identification of nuclear factor-kappa B (NF-kappaB)
      inhibitors of QSYQ is generally lacking. Therefore, it is necessary to establish
      an effective method to screen the bioactive components of NF-kappaB inhibition.
      In the present study, a rat model of coronary artery ligation was used to assess
      the cardioprotective effects of QSYQ. The electrocardiograms, histopathology of
      heart tissues and serum biochemical indicators, such as brain natriuretic
      peptide, cardiac troponin I and inflammatory cytokines, were measured.
      Subsequently, ultra-performance liquid chromatography quadrupole/time-of-flight
      mass spectrometry (UPLC-Q/TOF MS) combined with the NF-kappaB luciferase reporter
      assay system was applied to screen the potential anti-inflammatory compounds in
      QSYQ. The results revealed that the administration of QSYQ could improve heart
      function, ameliorate neutrophil infiltration and diminish the levels of
      inflammatory cytokines in MI rats. Furthermore, 22 compounds were determined to
      be potential NF-kappaB inhibitors. In conclusion, NF-kappaB inactivation and
      cytokine suppression might be the main mechanisms of QSYQ for MI treatment. The
      method of UPLC-Q/TOF MS combined with a bioactive human cell functional
      evaluation system was proved to be a simple and effective strategy for screening
      bioactive compounds in traditional Chinese medicine prescriptions.

PMID- 25845700
TI  - Twins' risk of childhood asthma mediated by gestational age and birthweight.
AB  - BACKGROUND: Children born with low gestational age (GA) or low birthweight (BW)
      are at increased risk of asthma. Twins as compared to singletons are on average
      more likely to be born with lower GA and BW and have been hypothesized to
      comprise a high-risk population for asthma. Many previous studies have not
      accounted for potential confounders or mediators. OBJECTIVE: To investigate the
      association between twinship and childhood asthma or early life wheeze and
      identify potential mediators, such as GA/BW. METHODS: The study population
      consisted of two cohorts including all children born in Sweden from 1 January
      1993 to 1 June 2001 (n = 756,363 singletons, n = 22,478 twins) and 1 July 2005 to
      31 December 2009 (n = 456,239 singletons, n = 12,872 twins). Asthma was defined
      using validated register-based outcomes of diagnosis or medication. The data were
      analysed using logistic (older cohort) and Cox regression (younger cohort).
      Adjusted models incorporated potential confounding or mediating factors including
      gestational age and birthweight. RESULTS: In the younger cohort, the crude hazard
      ratio (HR) of asthma medication after 1.5 years of age was 1.12 (95% CI 1.01
      1.23), and fully adjusted HR was 0.80, 95% CI 0.72-0.89. Crude HR of asthma
      diagnosis in the same age group was 1.14 (95% CI 0.99-1.30), fully adjusted 0.78
      (0.68-0.98). Adjusted analyses in the older group yielded similar results.
      CONCLUSIONS: Twins were at significantly higher unadjusted risk of asthma or
      early life wheeze compared to singletons in the younger, but not in the older
      cohort. Associations attenuated following adjustment for GA/BW, suggesting that
      GA/BW mediates the effect of twinship on asthma risk. After adjustments, twins
      were at lower risk of asthma outcomes, possibly due to unmeasured confounding.

PMID- 25845701
TI  - Peritumoral dermis of squamous cell carcinomas in renal transplant recipients
      contains less CD11c+ myeloid dendritic cells and FoxP3+ T cells compared to
      immunocompetent controls.
AB  - BACKGROUND: Renal transplant recipients (RTR) have an increased risk of
      developing cutaneous squamous cell carcinomas (SCC). These SCC are often more
      aggressive than SCC in immunocompetent individuals. OBJECTIVES: In this
      comparative study, we analysed the cell composition in the tissue immediately
      surrounding invasive SCC in immunosuppressed RTR and immunocompetent controls in
      an effort to further elucidate the role of the local immune system. METHODS:
      Morphology and quantity of various dendritic cell (DC) subsets, macrophages and
      FoxP3+ T cells were analysed by immunohistochemical staining. RESULTS: The number
      of CD11c+ myeloid DC and FoxP3+ T cells was significantly reduced in RTR, whereas
      the number of plasmacytoid DC, Langerhans cells and macrophages was similar in
      RTR and controls. CONCLUSIONS: A reduction in CD11c+ mDC in peritumoral dermis in
      RTR might contribute to impaired immunosurveillance thus giving rise to an
      increased risk to develop aggressive SCC in these patients.

PMID- 25845702
TI  - Histidine-modified organic-silica hybrid monolithic column for mixed-mode per
      aqueous and ion-exchange capillary electrochromatography.
AB  - A novel organic-silica hybrid monolith was prepared through the binding of
      histidine onto the surface of monolithic matrix for mixed-mode per aqueous and
      ion-exchange capillary electrochromatography. The imidazolium and amino groups on
      the surface of the monolithic stationary phase were used to generate an anodic
      electro-osmotic flow as well as to provide electrostatic interaction sites for
      the charged compounds at low pH. Typical per aqueous chromatographic behavior was
      observed in water-rich mobile phases. Various polar and hydrophilic analytes were
      selected to evaluate the characteristics and chromatographic performance of the
      obtained monolith. Under per aqueous conditions, the mixed-mode mechanism of
      hydrophobic and ion-exchange interactions was observed and the resultant
      monolithic column proved to be very versatile for the efficient separations of
      these polar and hydrophilic compounds (including amides, nucleosides and
      nucleotide bases, benzoic acid derivatives, and amino acids) in highly aqueous
      mobile phases. The successful applications suggested that the histidine-modified
      organic-silica hybrid monolithic column could offer a wide range of retention
      behaviors and flexible selectivities toward polar and hydrophilic compounds. 

PMID- 25845703
TI  - The early Pleistocene deciduous hominid molar FS-72 from the Sangiran Dome of
      Java, Indonesia: A taxonomic reappraisal based on its comparative endostructural
      characterization.
AB  - OBJECTIVES: Among the ten fossil hominid deciduous teeth reported so far from the
      Pleistocene sediments of the Sangiran Dome of Java are two isolated lower second
      molars: specimens PCG.2 from the Kabuh Formation and FS-72 from the Pucangan
      Formation. While PCG.2 appears to be certainly attributable to Homo erectus, FS
      72 is somewhat more problematic, even though it is commonly listed within the
      Indonesian H. erectus hypodigm. Largely because of its large size, it was
      originally attributed to Meganthropus paleojavanicus. Subsequent study
      highlighted a set of metric and nonmetric crown features also found in
      Australopith and African early Homo (notably H. habilis) homologues. An
      additional problem with the taxonomic assignment of isolated teeth from the
      Pleistocene of Java is the presence of Pongo in these same deposits. METHODS: To
      assess the taxonomic affinity of FS-72, we investigated its inner structure
      (tissue proportions and enamel-dentine junction morphology) by using techniques
      of 2-3D virtual imaging coupled with geometric morphometric analyses. RESULTS:
      The results show that FS-72 has thinner enamel compared to fossil and recent
      humans and that its topographic repartition more closely follows the pongine
      pattern. It also exhibits a Pongo-like elongated morphology of the enamel-dentine
      junction, with proportionally lower and mesiodistally spaced dentine horns.
      CONCLUSIONS: Given the morphological and metric similarities between fossil
      orangutan and H. erectus molars, we tested the hypothesis that its internal
      morphology more closely resembles the patterns evinced by PCG.2 and modern humans
      than Pongo. Accordingly, we consider that FS-72 more likely represents a dm2 of
      Pongo rather than Homo.

PMID- 25845704
TI  - D-dimers Are a Predictor of Clot Volume Inside Membrane Oxygenators During
      Extracorporeal Membrane Oxygenation.
AB  - Thrombosis inside the membrane oxygenator (MO) is a critical complication during
      venovenous extracorporeal membrane oxygenation (ECMO). The aim of this study was
      to prove if thrombotic clots manifest within the MO when D-dimer levels are
      elevated over a long-term period. Heparin-coated polymethylpentene MOs (n = 13)
      were exchanged due to high plasma D-dimer levels. Clot volume was calculated
      using multidetector computed tomography (MDCT). Coagulation parameters and MO
      function were analyzed before and after MO exchange. Before MO exchange, D-dimer
      levels increased significantly in each patient (11.5 [6.5-15.5] mg/L to 35.0 [34
      35] mg/L, P <= 0.001). High levels of D-dimers were tolerated for 1 to 6 days.
      Additionally, fibrinogen concentration (n = 8) and platelet count decreased (n =
      8). Within 48 h after exchange, D-dimer levels decreased significantly (n = 11,
      12 [8-16] mg/L, P = 0.004). Fibrinogen concentration and platelet counts
      increased. Clots were found in all MOs in the inlet part of the device. Clot
      volume (16-106 cm(3) ) did not correlate with MO support time but increased
      significantly when high D-dimer levels were accepted for >2 days. An increase or
      high levels of D-dimers in absence of other explaining pathology during ECMO
      therapy reflected coagulation activity within the MO. Evidence of clots within
      the MO at high D-dimer levels and decrease after exchange underline the relevance
      of D-dimer testing during ECMO treatment. Besides, surveillance of MOs during
      ongoing ECMO therapy will help to predict clot formation, and to avoid system
      induced coagulation disorders as well as critical situations. 

PMID- 25845706
TI  - Strongly bias-dependent tunnel magnetoresistance in manganite spin filter tunnel
      junctions.
AB  - A highly unconventional bias-dependent tunnel magnetoresistance (TMR) response is
      observed in Sm0.75 Sr0.25 MnO3 -based nanopillar spin filter tunnel junctions
      (SFTJs) with two different behaviors in two different thickness regimes of the
      barrier layer. Thinner barrier devices exhibit conventional SFTJ behaviors;
      however, for larger barrier thicknesses, the TMR-bias dependence is more complex
      and reverses sign at higher bias. 

PMID- 25845705
TI  - Measurement of 25-hydroxyvitamin D(2&3) and 1,25-dihydroxyvitamin D(2&3) by
      tandem mass spectrometry: A primate multispecies comparison.
AB  - Vitamin D metabolites are widely studied for their roles in bone health, immune
      functions, and other potential physiologic roles in humans. However, the optimal
      blood levels of vitamin D metabolites are still unclear. Various methods for
      measuring vitamin D metabolites have been used and recently liquid chromatography
      tandem mass spectroscopy (LC-MS/MS) has been adopted as the gold standard for
      vitamin D metabolite measurement. Here, we report the use of LC-MS/MS to measure
      25-hydroxyvitamin D (25(OH)D(2&3)), and 1,25-dihydroxyvitamin D
      (1,25(OH)2D(2&3)), in three laboratory nonhuman primate species: common marmoset
      (Callithrix jacchus), rhesus macaque (Macaca mulatta), and cynomolgus macaque
      (Macaca fascicularis), and compare them to humans using the same technique. The
      nonhuman primates showed blood levels for 25(OH)D3 and 1,25(OH)2D3 significantly
      higher than human values with marmosets having the highest levels. Marmoset
      samples showed significantly more variability among individuals than those from
      macaques for both metabolites, but all three nonhuman primate species exhibited
      large variation within species for both 25(OH)D(2&3) and 1,25(OH)2D(2&3).
      Marmoset females had significantly lower values than the males for 25(OH)D3,
      while rhesus males showed a significant decrease in 25(OH)D3 with age. The most
      striking finding is the variation within species for vitamin D levels even in
      laboratory primates that have a controlled diet, UV exposure, and in some cases,
      genetic constraints. Similar variation in 25(OH)D responses to a fixed dose of
      oral vitamin D supplementation has been reported in humans. We suggest that these
      species can provide primate models for examining the factors influencing
      variation in the levels of vitamin D necessary for human and nonhuman primate
      health.

PMID- 25845707
TI  - Spinal cord neuron inputs to the cuneate nucleus that partially survive dorsal
      column lesions: A pathway that could contribute to recovery after spinal cord
      injury.
AB  - Dorsal column lesions at a high cervical level deprive the cuneate nucleus and
      much of the somatosensory system of its major cutaneous inputs. Over weeks of
      recovery, much of the hand representations in the contralateral cortex are
      reactivated. One possibility for such cortical reactivation by hand afferents is
      that preserved second-order spinal cord neurons reach the cuneate nucleus through
      pathways that circumvent the dorsal column lesions, contributing to cortical
      reactivation in an increasingly effective manner over time. To evaluate this
      possibility, we first injected anatomical tracers into the cuneate nucleus and
      plotted the distributions of labeled spinal cord neurons and fibers in control
      monkeys. Large numbers of neurons in the dorsal horn of the cervical spinal cord
      were labeled, especially ipsilaterally in lamina IV. Labeled fibers were
      distributed in the cuneate fasciculus and lateral funiculus. In three other
      squirrel monkeys, unilateral dorsal column lesions were placed at the cervical
      segment 4 level and tracers were injected into the ipsilateral cuneate nucleus.
      Two weeks later, a largely unresponsive hand representation in contralateral
      somatosensory cortex confirmed the effectiveness of the dorsal column lesion.
      However, tracer injections in the cuneate nucleus labeled only about 5% of the
      normal number of dorsal horn neurons, mainly in lamina IV, below the level of
      lesions. Our results revealed a small second-order pathway to the cuneate nucleus
      that survives high cervical dorsal column lesions by traveling in the lateral
      funiculus. This could be important for cortical reactivation by hand afferents,
      and recovery of hand use.

PMID- 25845708
TI  - Prospective study of Helicobacter pylori antigens and gastric noncardia cancer
      risk in the nutrition intervention trial cohort.
AB  - Helicobacter pylori (H. pylori) infection is the strongest known risk factor for
      gastric noncardia adenocarcinoma (GNCA). We used multiplex serology to determine
      whether seropositivity to 15 H. pylori proteins is associated with the subsequent
      development of noncardia gastric cancer in Linxian, China. We included 448 GNCA
      cases and 1242 controls from two time points within the Linxian General
      Population Nutrition Intervention Trial, Linxian. H. pylori multiplex
      seropositivity was defined as positivity to >=4 of the 15 included antigens. Odds
      ratios (ORs) and 95% confidence intervals (CIs) were adjusted for major GNCA risk
      factors. In addition, we undertook a meta-analysis combining H. pylori multiplex
      serology data from both time points. H. pylori multiplex seropositivity was
      associated with a significant increase in risk of GNCA at one time point (1985;
      OR: 3.44, 95% CI: 1.91, 6.19) and this association remained significant following
      adjustment for H. pylori or CagA ELISA seropositivity (OR: 2.92, 95% CI: 1.56,
      5.47). Combining data from both time points in a meta-analysis H. pylori
      multiplex seropositivity was associated with an increased risk of GNCA, as were
      six individual antigens: GroEL, HP0305, CagA, VacA, HcpC and Omp. CagM was
      inversely associated with risk of GNCA. We identified six individual antigens
      that confer an increase in risk of GNCA within this population of high H. pylori
      seroprevalence, as well as a single antigen that may be inversely associated with
      GNCA risk. We further determined that the H. pylori multiplex assay provides
      additional information to the conventional ELISA methods on risk of GNCA. 

PMID- 25845709
TI  - Impact of quality improvement measures on the delivery of allergy immunotherapy:
      a 2-year follow-up.
AB  - BACKGROUND: Anaphylaxis is the most serious potential complication from allergy
      treatment with subcutaneous immunotherapy (SCIT). Quality measures were developed
      with the goal to decrease the incidence of complications resulting from SCIT and
      improve the safety of care provided. METHODS: The incidence and characteristics
      of anaphylaxis episodes resulting from SCIT was measured between 2008 and 2012
      prior to implementation of quality measures including vial verification, vial
      testing, and standardized training across 6 allergy delivery sites. Errors and
      anaphylaxis rates were then tracked prospectively over a 2-year period after
      implementation of these process measures. RESULTS: From 2008 to 2012 there were 9
      episodes of anaphylaxis or 0.02% of injections/year. Eight patients had
      sufficient information from which to derive meaningful data. Patient
      identification error led to anaphylaxis in 2 patients, dosing error in 2, and
      compounding error in 1 patient. In 2 patients, anaphylaxis occurred with
      advancement during pollen season, and in 1 patient no clear reason could be
      identified although she had asthma as a risk factor. After implementation of
      quality improvement measures the anaphylaxis rate fell to 0 of 8948 injections
      for years 2013 and 2014. CONCLUSION: Errors in the mixing and administration of
      allergy serum comprised the majority of identifiable factors that led to
      anaphylaxis. Implementation of quality measures, including vial verification and
      vial testing, can improve safety and decrease anaphylaxis rates in the delivery
      of allergy immunotherapy.

PMID- 25845710
TI  - APPROXIMATING A DSM-5 DIAGNOSIS OF PTSD USING DSM-IV CRITERIA.
AB  - BACKGROUND: Diagnostic criteria for DSM-5 posttraumatic stress disorder (PTSD)
      are in many ways similar to DSM-IV criteria, raising the possibility that it
      might be possible to closely approximate DSM-5 diagnoses using DSM-IV symptoms.
      If so, the resulting transformation rules could be used to pool research data
      based on the two criteria sets. METHODS: The pre-post deployment study (PPDS) of
      the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS)
      administered a blended 30-day DSM-IV and DSM-5 PTSD symptom assessment based on
      the civilian PTSD Checklist for DSM-IV (PCL-C) and the PTSD Checklist for DSM-5
      (PCL-5). This assessment was completed by 9,193 soldiers from three US Army
      Brigade Combat Teams approximately 3 months after returning from Afghanistan. PCL
      C items were used to operationalize conservative and broad approximations of DSM
      5 PTSD diagnoses. The operating characteristics of these approximations were
      examined compared to diagnoses based on actual DSM-5 criteria. RESULTS: The
      estimated 30-day prevalence of DSM-5 PTSD based on conservative (4.3%) and broad
      (4.7%) approximations of DSM-5 criteria using DSM-IV symptom assessments were
      similar to estimates based on actual DSM-5 criteria (4.6%). Both approximations
      had excellent sensitivity (92.6-95.5%), specificity (99.6-99.9%), total
      classification accuracy (99.4-99.6%), and area under the receiver operating
      characteristic curve (0.96-0.98). CONCLUSIONS: DSM-IV symptoms can be used to
      approximate DSM-5 diagnoses of PTSD among recently deployed soldiers, making it
      possible to recode symptom-level data from earlier DSM-IV studies to draw
      inferences about DSM-5 PTSD. However, replication is needed in broader trauma
      exposed samples to evaluate the external validity of this finding.

PMID- 25845711
TI  - Increased risk of portal vein thrombosis in patients with cirrhosis due to
      nonalcoholic steatohepatitis.
AB  - Portal vein thrombosis (PVT) is a common complication of cirrhosis sometimes
      implicated in hepatic decompensation. There are no consistent epidemiologic data
      to suggest an increased risk of thrombotic complications in nonalcoholic
      steatohepatitis (NASH); however, research suggests an increased risk of
      thrombosis. Our aim was to examine the independent association between NASH
      cirrhosis and PVT in patients who underwent liver transplantation (LT) in a cross
      sectional study. Data on all LTs occurring in the United States between January
      1, 2003 and December 31, 2012 were obtained from the United Network for Organ
      Sharing. Multivariable models were constructed to assess the statistical
      associations and risk factors for the development of PVT. A total of 33,368
      patients underwent transplantation. Of these, 2096 (6.3%) had PVT. Of the
      patients with PVT, 12.0% had NASH. When we compared these patients to a composite
      of all other causes of cirrhosis, an increased prevalence of PVT was again found,
      with 10.1% having PVT at the time of transplantation versus 6.0% without NASH (P
      < 0.001). The strongest risk factor independently associated with a diagnosis of
      PVT in a multivariable analysis was NASH cirrhosis (odds ratio, 1.55; 95%
      confidence interval, 1.33-1.81; P < 0.001). NASH cirrhosis appears to predispose
      a patient to PVT independently of other risk factors. These epidemiological
      findings provide support for the idea that NASH is a prothrombotic state, and
      they should lead to more research in treatment and prevention in this population.

PMID- 25845712
TI  - 12q21.2q22 deletion: a new patient.
AB  - Interstitial deletions of long arm of chromosome 12 are rare, and the
      interstitial deletion 12q21.1q22 has been reported to the best of our knowledge
      in only four patients. Comparing the patients reported, a characteristic
      phenotypic pattern (facial features like prominent forehead, short and upturned
      nose, low set ears, and ectodermal abnormalities) can be identified. It has been
      suggested to be considered a deletion syndrome [Klein et al., (2005); Am J Med
      Genet 138:349-354]. We report on a 34-month-old girl, who was referred to our
      clinic at 6 months of age, presenting at birth with axial hypotonia, enlarged
      anterior fontanel, ventriculomegaly, dysmorphic facies (prominent forehead,
      sparse hair and eyebrows, short palpebral fissures), failure to thrive and
      development delay. Her cytogenetic study showed an interstitial deletion of the
      long arm of chromosome 12: 46,XX,del(12)(q21.1q22) redefined by array comparative
      genomic hybridization. We compare and review our patient with the four previously
      reported cases, plus one with a deletion with an overlap of the chromosomal
      region and phenotypic similarities. As far as we know our patient is the fourth
      reported with this cytogenetic abnormality. This additional report allows us to
      support a genotype-phenotype correlation for this chromosomal abnormality.

PMID- 25845713
TI  - Sensitivity of chemical shift-encoded fat quantification to calibration of fat MR
      spectrum.
AB  - PURPOSE: To evaluate the impact of different fat spectral models on proton
      density fat fraction quantification using chemical shift-encoded MRI (CSE-MRI).
      METHODS: In a simulation study, spectral models of fat were compared pairwise.
      Comparison of magnitude fitting and mixed fitting was performed over a range of
      echo times and fat fractions. In vivo acquisitions from 41 patients were
      reconstructed using seven published spectral models of fat. T2-corrected
      stimulated echo acquisition mode MR spectroscopy was used as a reference.
      RESULTS: The simulations demonstrated that imperfectly calibrated spectral models
      of fat result in biases that depend on echo times and fat fraction. Mixed fitting
      was more robust against this bias than magnitude fitting. Multipeak spectral
      models showed much smaller differences among themselves than from the single-peak
      spectral model. In vivo studies showed that all multipeak models agreed better
      (for mixed fitting, the slope ranged from 0.967 to 1.045 using linear regression)
      with the reference standard than the single-peak model (for mixed fitting, slope
      = 0.76). CONCLUSION: It is essential to use a multipeak fat model for accurate
      quantification of fat with CSE-MRI. Furthermore, fat quantification techniques
      using multipeak fat models are comparable, and no specific choice of spectral
      model has been shown to be superior to the rest.

PMID- 25845714
TI  - Off-label use of nicardipine as tocolytic and acute pulmonary oedema: a post
      marketing analysis of adverse drug reaction reports in EudraVigilance.
AB  - PURPOSE: To evaluate a signal of acute pulmonary oedema (APO) due to nicardipine
      used off-label as tocolytic in pregnant women. METHODS: All the suspected cases
      of APO recorded in EudraVigilance database up to 31/01/2013 and associated with
      nicardipine containing medicinal products were retrieved. The Proportional
      Reporting Ratio was considered as measure of disproportionality. Individual cases
      evaluation was conducted. RESULTS: Thirty-four spontaneous cases regarding
      pregnancy women who experienced APO following nicardipine treatment as tocolytic
      were collected. The detected proportional reporting ratio was 50.96 (95%
      confidence interval lower bound equal to 36.75). The analysis focused on 10
      serious cases. Most women, aged between 27 and 39 years, were treated with
      intravenous nicardipine. The most of the suspected adverse reactions occurred
      between 24 and 96 hours. CONCLUSIONS: A potentially causal association between
      APO and off-label use of nicardipine as tocolytic has been detected during a
      periodic signal detection activity. The Pharmacovigilance Risk Assessment
      Committee confirmed our findings, recommending an update of the summary of the
      product characteristics for medicines containing nicardipine for both intravenous
      and oral formulations. Then European Medicines Agency reaffirmed that nicardipine
      use in other indications is no longer recommended.

PMID- 25845715
TI  - Endovascular Therapy for Acute Ischemic Stroke: Time to Enter a New Era in Stroke
      Management.

PMID- 25845716
TI  - Omega-3 eicosatetraenoic acid production by molecular breeding of the mutant
      strain S14 derived from Mortierella alpina 1S-4.
AB  - We investigated the omega-3 eicosatetraenoic acid (ETA) production by molecular
      breeding of the oleaginous fungus Mortierella alpina, which can slightly
      accumulate ETA only when cultivated at a low temperature. The endogenous omega3
      desaturase gene or the heterologous Saprolegnia diclina Delta17 (sdd17m)
      desaturase gene were overexpressed in M. alpina S14, a Delta5-desaturation
      activity-defective mutant derived from M. alpina 1S-4. M. alpina S14
      transformants introduced with the endogenous omega3-desaturase gene showed ETA at
      42.1% content in the total lipids that was 84.2-fold and 3.2-fold higher than
      that of the wild-type strain 1S-4 and host strain S14, respectively, when
      cultivated at 12 degrees C. No accumulation of ETA was observed at 28 degrees C.
      In contrast, transformants with the heterologous sdd17m gene showed 24.9% of the
      content of total lipids at 28 degrees C. These results indicated that these M.
      alpina S14 transformants are promising strains for the production of ETA, which
      is hard to obtain from natural sources. 

PMID- 25845717
TI  - Systematic identification of thermal degradation products of HPMCP during hot
      melt extrusion process.
AB  - A systematic identification of the degradation products of hydroxypropyl
      methylcellulose phthalate (HPMCP) during hot melt extrusion (HME) has been
      performed. A reverse phase HPLC method was developed for the extrudates of both
      hydroxypropyl methylcellulose acetate succinate (HPMCAS) and HPMCP polymers to
      quantify their thermal hydrolytic products: acetic acid (AA), succinic acid (SA)
      for HPMCAS and phthalic acid (PA) for HPMCP, without hydrolysing the polymers in
      strong alkaline solutions. The polymers were extruded in the temperature range of
      160-190  degrees C at different screw rotation speeds and hydrolytic impurities
      were analysed. Investigation of extruded HPMCP showed an additional thermal
      degradation product, who is structural elucidation revealed to be phthalic
      anhydride (PAH). Moreover, two environmental analytical impurities, dimethyl
      phthalate and methyl benzoate formed in situ were recorded on GC-MS and their
      origin was found to be associated with PAH derivatization. Using the experimental
      data gathered during this study, a degradation mechanism for HPMCP is proposed.

PMID- 25845718
TI  - DEM analysis of the effect of particle-wall impact on the dispersion performance
      in carrier-based dry powder inhalers.
AB  - The impact between particles or agglomerates and a device wall is considered as
      an important mechanism controlling the dispersion of active pharmaceutical
      ingredient (API) particles in dry powder inhalers (DPIs). In order to
      characterise the influencing factors and better understand the impact induced
      dispersion process for carrier-based DPIs, the impact behaviour between an
      agglomerate and a wall is systematically investigated using the discrete element
      method. In this study, a carrier-based agglomerate is initially formed and then
      allowed to impact with a target wall. The effects of impact velocity, impact
      angle and work of adhesion on the dispersion performance are analysed. It is
      shown that API particles in the near-wall regions are more likely to be dispersed
      due to the deceleration of the carrier particle resulted from the impact with the
      wall. It is also revealed that the dispersion ratio increases with increasing
      impact velocity and impact angle, indicating that the normal component of the
      impact velocity plays a dominant role on the dispersion. Furthermore, the impact
      induced dispersion performance for carrier-based DPI formulations can be well
      approximated using a cumulative Weibull distribution function that is governed by
      the ratio of overall impact energy and adhesion energy. 

PMID- 25845719
TI  - Risk assessment of nanoformulations.

PMID- 25845721
TI  - Physiological effects of polybrominated diphenyl ether (PBDE-47) on pregnant
      gartersnakes and resulting offspring.
AB  - Polybrominated diphenyl ethers (PBDEs) are used as flame retardants and are
      persistent contaminants found in virtually every environment and organism sampled
      to date, including humans. There is growing evidence that PBDEs are the source of
      thyroid, neurodevelopmental, and reproductive toxicity. Yet little work has
      focused on how this pervasive contaminant may influence the reproduction and
      physiology of non-traditional model species. This is especially critical because
      in many cases non-model species, such as reptiles, are most likely to come into
      contact with PBDEs in nature. We tested how short-term, repeated exposure to the
      PBDE congener BDE-47 during pregnancy affected physiological processes in
      pregnant female gartersnakes (thyroid follicular height, bactericidal ability,
      stress responsiveness, reproductive output, and tendency to terminate pregnancy)
      and their resulting offspring (levels of corticosterone, bactericidal ability,
      and size differences). We found potential effects of BDE-47 on both the mother,
      such as increased size and higher thyroid follicular height, and her offspring
      (increased size), suggesting the effects on physiological function of PBDEs do
      indeed extend beyond the traditional rodent models. 

PMID- 25845720
TI  - A novel in vitro assay for assessing efficacy and toxicity of antifungals using
      human leukaemic cells infected with Candida albicans.
AB  - AIMS: This study describes a novel in vitro assay that simultaneously determines
      antifungal efficiency and host cell toxicity using suspensions of human leukaemic
      cells (HL-60) infected with Candida albicans. METHODS AND RESULTS: The effect of
      Candida infection on host cell viability was evaluated by the microscopy of
      trypan blue-stained cells and lactate dehydrogenase (LDH) activity. The in vitro
      'drug potency assay' utilized the Cell Counting Kit-8 and measured post
      antifungal treatment viability of Candida-infected HL-60 cells and the ability of
      the antifungal treatment to prevent infection. LDH activity showed that 42% +/-
      4.0 and 85.3% +/- 7.40 of HL-60 cells were killed following Candida infection at
      the multiplicity of infection (MOI) of 1 : 1 and 1 : 5, respectively. The
      antifungal nystatin (0.78-25 MUmol l(-1) ) was found to inhibit C. albicans
      infection as seen by the significantly increased viability of HL-60 cells.
      Cytotoxicity of nystatin towards infected HL-60 cells was evident at higher
      concentrations and this was also confirmed by propidium iodide staining.
      CONCLUSIONS: An assay using undisturbed cell suspension conditions was
      successfully developed for assessing the selectivity of the antifungal therapy in
      the host-Candida environment. SIGNIFICANCE AND IMPACT OF THE STUDY: The assay
      employing Candida infection of host cell suspensions represents a promising
      method for testing interactions of antifungal compounds with both fungal and host
      cells.

PMID- 25845722
TI  - Rice endosperm produces an underglycosylated and potent form of the HIV
      neutralizing monoclonal antibody 2G12.
AB  - Protein microbicides against HIV can help to prevent infection but they are
      required in large, repetitive doses. This makes current fermenter-based
      production systems prohibitively expensive. Plants are advantageous as production
      platforms because they offer a safe, economical and scalable alternative, and
      cereals such as rice are particularly attractive because they could allow
      pharmaceutical proteins to be produced economically and on a large scale in
      developing countries. Pharmaceutical proteins can also be stored as unprocessed
      seed, circumventing the need for a cold chain. Here, we report the development of
      transgenic rice plants expressing the HIV-neutralizing antibody 2G12 in the
      endosperm. Surprisingly for an antibody expressed in plants, the heavy chain was
      predominantly aglycosylated. Nevertheless, the heavy and light chains assembled
      into functional antibodies with more potent HIV-neutralizing activity than other
      plant-derived forms of 2G12 bearing typical high-mannose or plant complex-type
      glycans. Immunolocalization experiments showed that the assembled antibody
      accumulated predominantly in protein storage vacuoles but also induced the
      formation of novel, spherical storage compartments surrounded by ribosomes
      indicating that they originated from the endoplasmic reticulum. The comparison of
      wild-type and transgenic plants at the transcriptomic and proteomic levels
      indicated that endogenous genes related to starch biosynthesis were down
      regulated in the endosperm of the transgenic plants, whereas genes encoding
      prolamin and glutaredoxin-C8 were up-regulated. Our data provide insight into
      factors that affect the functional efficacy of neutralizing antibodies in plants
      and the impact of recombinant proteins on endogenous gene expression. 

PMID- 25845723
TI  - Surveillance versus clinical adjudication: differences persist with new
      ventilator-associated event definition.
AB  - BACKGROUND: The National Healthcare Safety Network (NHSN) has recently supported
      efforts to shift surveillance away from ventilator-associated pneumonia to
      ventilator-associated events (VAEs) to decrease subjectivity in surveillance and
      minimize concerns over clinical correlation. The goals of this study were to
      compare the results of an automated surveillance strategy using the new VAE
      definition with a prospectively performed clinical application of the definition.
      METHODS: All patients ventilated for >=2 days in a medical and surgical intensive
      care unit were evaluated by 2 methods: retrospective surveillance using an
      automated algorithm combined with manual chart review after the NHSN's VAE
      methodology and prospective surveillance by pulmonary physicians in collaboration
      with the clinical team administering care to the patient at the bedside. RESULTS:
      Overall, a similar number of events were called by each method (69 vs 67). Of the
      1,209 patients, 56 were determined to have VAEs by both methods (kappa = .81, P =
      .04). There were 24 patients considered to be a VAE by only 1 of the methods.
      Most discrepancies were the result of clinical disagreement with the NHSN's VAE
      methodology. CONCLUSIONS: There was good agreement between the study teams.
      Awareness of the limitations of the surveillance definition for VAE can help
      infection prevention personnel in discussions with critical care partners about
      optimal use of these data.

PMID- 25845724
TI  - Contributing factors to star excursion balance test performance in individuals
      with chronic ankle instability.
AB  - The purpose of this study was to determine the contributions of strength,
      dorsiflexion range of motion (DFROM), plantar cutaneous sensation (PCS), and
      static postural control to Star Excursion Balance Test (SEBT) performance in
      individuals with chronic ankle instability (CAI). Forty individuals with CAI
      completed isometric strength, weight-bearing DFROM, PCS, static and dynamic
      balance assessments. Three separate backward multiple linear regression models
      were calculated to determine how strength, DFROM, PCS, and static postural
      control contributed to each reach direction of the SEBT. Explanatory variables
      included dorsiflexion, inversion, and eversion strength, DFROM, PCS, and time-to
      boundary mean minima (TTBMM) and standard deviation (TTBSD) in the medial-lateral
      (ML) and anterior-posterior (AP) directions. Criterion variables included SEBT
      anterior, posteromedial, and posterolateral directions. The strength of each
      model was determined by the R2-value and Cohen's f2 effect size. Regression
      models with an effect size >=0.15 were considered clinically relevant. All three
      SEBT directions produced clinically relevant regression models. DFROM and PCS
      accounted for 16% of the variance in SEBT-anterior reach (f2=0.19, p=0.04).
      Eversion strength and TTBMM-ML accounted for 28% of the variance in SEBT
      posteromedial reach (f2=0.39, p<0.01). Eversion strength and TTBSD-ML accounted
      for 14% of the variance in SEBT-posterolateral reach (f2=0.16, p=0.06). DFROM and
      PCS explained a clinically relevant proportion of the variance associated with
      SEBT-anterior reach. Eversion strength and TTB ML explained a clinically relevant
      proportion of the variance in SEBT-posteromedial and posterolateral reach
      distances. Therefore, rehabilitation strategies should emphasize DFROM, PCS,
      eversion strength, and static balance to enhance dynamic postural control in
      patients with CAI.

PMID- 25845733
TI  - Fine structure of the male genital system of the predatory mite Rhagidia
      halophila (Rhagidiidae, Prostigmata, Actinotrichida).
AB  - The male genital system of the actinotrichid mite Rhagidia halophila is described
      and compared with other mites and arachnids. The large testes are composed of
      germinal and glandular parts and produce numerous small sperm cells. The
      glandular parts are connected via a testicular bridge. Spermiogenesis occurs in
      cysts containing spermatids in equal stages of development. Cysts of spermatids
      are embedded in huge somatic cells. The nuclei of the spermatids loose their
      envelope. Mature sperm cells are simple exhibiting a ring-shaped chromatin body
      and lacking an acrosomal complex. They are most similar to the sperm cells of the
      related mite Linopodes motatorius. The spermatopositor contains the ejaculatory
      duct divided into a dorsal channel and a ventral channel that are connected via a
      narrow passage. At its distal end, the spermatopositor is divided into three
      eugenital lips. The function of the spermatopositor during deposition of the
      peculiar thread-like spermatophores is discussed. Details of the sensilla of the
      spermatopositor and the progenital lips are reported. The genital papillae
      located on the inner side of the progenital lips exhibit characteristics of cells
      performing transport of ions and/or water. The results confirm the overall
      similarity of actinotrichid genital systems, which is profoundly different from
      that of anactinotrichid mites. With reference to other Arachnida it is
      corroborated that testes and sperm structure of Actinotrichida are most similar
      to that of Solifugae. However, synapomorphies between sperm cells of Rhagidia and
      Solifugae that could suggest a closer relationship between these two taxa as was
      suggested in earlier studies were not recognizable. On the contrary, the sperm
      cells of Rh. halophila being devoid of an acrosomal complex appeared to be more
      apomorphic than those of many other actinotrichid mites as well as Solifugae.

PMID- 25845734
TI  - Parents' experiences when their child is undergoing an elective colonoscopy.
AB  - PURPOSE: The purpose was to illuminate parents' experiences when their children
      are undergoing an elective colonoscopy performed using polyethylene glycol-based
      regimes for bowel preparation. DESIGN AND METHODS: Individual interviews with 12
      parents were performed and analysed using content analysis. RESULTS: The parents'
      experiences were structured into one theme: "Charged with conflicting emotions"
      with three categories: "Being forced to force," "Losing one's sense of being a
      parent" and "Standing without guidance." PRACTICE IMPLICATIONS: Understanding
      parents' experiences can help healthcare staff guide parents in helping their
      children undergo a colonoscopy.

PMID- 25845735
TI  - rRNA regulation during growth and under stringent conditions in Staphylococcus
      aureus.
AB  - The control of rRNA synthesis and, thereby, translation is vital for adapting to
      changing environmental conditions. The decrease of rRNA is a common feature of
      the stringent response, which is elicited by the rapid synthesis of (p)ppGpp.
      Here we analysed the properties and regulation of one representative rRNA operon
      of Staphylococcus aureus under stringent conditions and during growth. The
      promoters, P1 and P2, are severely downregulated at low intracellular guanosine
      triphosphate (GTP) concentrations either imposed by stringent conditions or in a
      guanine auxotroph guaBA mutant. In a (p)ppGpp(0) strain, the GTP level increased
      under stringent conditions, and rRNA transcription was upregulated. The
      correlation of the intracellular GTP levels and rRNA promoter activity could be
      linked to GTP nucleotides in the initiation region of both promoters at positions
      between +1 and +4. This indicates that not only transcriptional initiation, but
      also the first steps of elongation, requires high concentrations of free
      nucleotides. However, the severe downregulation of rRNA in post-exponential
      growth phase is independent of (p)ppGpp, the composition of the initiation region
      and the intracellular nucleotide pool. In summary, rRNA transcription in S.
      aureus is only partially and presumably indirectly controlled by (p)ppGpp. 

PMID- 25845736
TI  - Support for down-staging of pregnancy-associated cervical cancer.
AB  - OBJECTIVE: To evaluate all cases of cervical cancer associated with pregnancy
      during 16 years in the Western Region of Sweden. DESIGN: Retrospective,
      descriptive cohort study. SETTING AND POPULATION: All women with cervical cancer,
      diagnosed during pregnancy or within 6 months after parturition, between 1993 and
      2008. METHODS: The study was based on data from different registers and medical
      records. MAIN OUTCOME MEASURES: Incidence, diagnostic measures, treatment and
      outcome of disease. RESULTS: Cervical cancer was diagnosed in 47 women (15.6/100
      000 deliveries). Sixteen women had abnormal vaginal bleeding and/or discharge.
      The other women were asymptomatic and diagnosed by abnormal cervical smear or
      clinical signs at vaginal examination. Nine women had atypical squamous cells of
      uncertain significance as presenting by cervical atypia. Twenty-two women had
      stage IA, 17 stage IB1, six stage IB2 and two stage IIA cancer. Cancer was
      diagnosed in the first trimester in two, in the second trimester in 14, in the
      third trimester in five and postpartum in 26 women. Histology revealed squamous
      cell carcinoma in 36 women, adenocarcinoma in eight, and adenosquamous carcinoma
      in three. Twenty women underwent cesarean section due to diagnosed or clinically
      suspected cancer, combined with the Wertheim-Meigs radical hysterectomy in six
      women. Sixteen women with stage IA1 cancer without signs of vascular invasion
      underwent conization as definitive therapy. Six women died of the disease.
      CONCLUSION: Early detection of cervical cytological atypia and proper follow-up
      during pregnancy led to detection of a high proportion of stage I cancer cases,
      which could be cured with fertility-sparing therapy.

PMID- 25845737
TI  - Complex assessment of distinct cognitive impairments following ouabain injection
      into the rat dorsoloateral striatum.
AB  - A stroke in humans may induce focal injury to the brain tissue resulting in
      various disabilities. Although motor deficits are the most discernible, cognitive
      impairments seem to be crucial for patients mental well-being. The current lack
      of effective treatments encourages scientists and clinicians to develop novel
      approaches. Before applying them in clinic, testing for safety and effectiveness
      in non-human models is necessary. Such animal model should include significant
      cognitive impairments resulting from brain lesion. We used ouabain stereotactic
      injection into the right dorsolateral striatum of male Wistar rats, and enriched
      environment housing. To confirm the brain injury before cognitive testing, rats
      were given a beam-walking task to evaluate the level of sensorimotor deficits. To
      determine the cognitive impairment after focal brain damage, rats underwent a set
      of selected tasks over an observation period of 30 days. Brain injury induced by
      ouabain significantly impaired the acquisition of the T-maze habit learning task,
      where 'win-stay' strategy rules were applied. The injured rats also showed
      significant deficits in the performance of the T-maze switching task, which
      involved shifting from multiple clues previously relevant to the only one
      important clue. Focal brain injury also significantly changed 'what--where'
      memory, tested in the object exploration task, in which a novel object
      consecutively appeared in the same place while the location of a familiar item
      was continuously changed. In conclusion, we developed an animal model of distinct
      cognitive impairments after focal brain injury that provides a convenient method
      to test the effectiveness of restorative therapies.

PMID- 25845738
TI  - Studies on the animal model of post-stroke depression and application of
      antipsychotic aripiprazole.
AB  - We investigated the question of whether an animal model of post-stroke depression
      in ischemic stroke can be developed by additional chronic mild stress (CMS)
      procedures. Behavioral and histopathological analysis was performed for
      examination of the depressive disorders in CMS, left middle cerebral artery
      occlusion (MCAO) and CMS after MCAO (MCAO+CMS) in mice. In all depressant
      screening tests involving open field, sucrose preference, forced swim and Morris
      water maze test, MCAO+CMS mice showed more significant depressive behaviors than
      MCAO mice. MCAO+CMS mice also showed distinct deficits in forced swim and Morris
      water maze test compared with CMS. In the histopathological analysis, prominent
      atrophic changes were seen in the striatum and midbrain of MCAO treated mice
      compared with CMS. MCAO+CMS mice showed a decrease of proliferative and
      differentiated neuronal cells in the striatum and hippocampus with dopaminergic
      neuronal injuries in the midbrain as compared with CMS and MCAO alone treated
      mice. Treatment of MCAO+CMS mice with aripiprazole resulted in reduction of all
      depressive behaviors examined, particularly in the Morris water maze test.
      Recovered dopaminergic neuronal injuries in the midbrain and enhanced
      neurogenesis in the hippocampus were also demonstrated. Our results suggest that
      CMS after ischemic stroke can lead to severe depressive-like behavior compared
      with CMS or MCAO alone treated mice via neurodegeneration in the primary lesion
      and secondary extrafocal sites and degradation of neurogenesis, and these
      behavioral and histopathological changes are reversed by treatment with
      aripiprazole. Thus adjunct therapy with an antipsychotic may exert its
      antidepressant effects via neuroprotection and neurogenesis in CMS-treated
      ischemic mice. 

PMID- 25845740
TI  - Gene-environment interaction of reelin and stress in cognitive behaviours in
      mice: Implications for schizophrenia.
AB  - Cognitive deficits are a particularly debilitating symptom group in
      schizophrenia. We investigated the effect of a 'two hit' combination of two
      factors implicated in schizophrenia development, reelin deficiency and stress, on
      cognitive behaviours in mice. Male and female heterozygous reelin mice (HRM) and
      wild-type (WT) controls received the stress hormone, corticosterone (CORT),
      during early adulthood to simulate chronic stress. The Y-maze, novel object
      recognition task (NORT), social interaction task and prepulse inhibition (PPI)
      were used to assess short-term spatial memory, visual non-spatial memory, social
      recognition memory and sensory gating, respectively. Reelin protein expression
      was measured in the prefrontal cortex (PFC) and hippocampus. CORT induced spatial
      memory deficits in male and female HRM but not in WT controls suggesting
      increased vulnerability of HRM to the effects of stress on cognition. By
      contrast, CORT disrupted PPI only in male WT mice, but not in male HRM,
      suggesting a protective role of reelin deficiency against effects of stress on
      PPI. Male HRM performed worse in the social recognition memory task compared to
      wild-type controls, irrespective of CORT treatment. No differences were detected
      in the NORT. Reelin protein expression was increased in the PFC of female CORT
      treated HRM but there were no group differences in the hippocampus. Overall,
      these findings extend our understanding of the role of reelin-stress interactions
      in schizophrenia. 

PMID- 25845739
TI  - Antidepressant activity of fluoxetine in the zinc deficiency model in rats
      involves the NMDA receptor complex.
AB  - The zinc deficiency animal model of depression has been proposed; however, it has
      not been validated in a detailed manner. We have recently shown that depression
      like behavior induced by dietary zinc restriction is associated with up
      regulation of hippocampal N-methyl-d-aspartate receptor (NMDAR). Here we examined
      the effects of chronic administration of a selective serotonin reuptake
      inhibitor, fluoxetine (FLX), on behavioral and biochemical alterations (within
      NMDAR signaling pathway) induced by zinc deficiency. Male Sprague Dawley rats
      were fed a zinc adequate diet (ZnA, 50mg Zn/kg) or a zinc deficient diet (ZnD,
      3mg Zn/kg) for 4 weeks. Then, FLX treatment (10mg/kg, i.p.) begun. Following 2
      weeks of FLX administration the behavior of the rats was examined in the forced
      swim test (FST) and the spontaneous locomotor activity test. Twenty four hours
      later tissue was harvested. The proteins of NMDAR (GluN1, GluN2A and GluN2B) or
      AMPAR (GluA1) subunits, p-CREB and BDNF in the hippocampus (Western blot) and
      serum zinc level (TXRF) were examined. Depression-like behavior induced by ZnD in
      the FST was sensitive to chronic treatment with FLX. ZnD increased levels of
      GluN1, GluN2A, GluN2B and decreased pS485-GluA1, p-CREB and BDNF proteins.
      Administration of FLX counteracted the zinc restriction-induced changes in serum
      zinc level and hippocampal GluN1, GluN2A, GluN2B and p-CREB but not BDNF or pS845
      GluA1 protein levels. This finding adds new evidence to the predictive validity
      of the proposed zinc deficiency model of depression. Antidepressant-like activity
      of FLX in the zinc deficiency model is associated with NMDAR complex.

PMID- 25845742
TI  - Unusual myocardial late gadolinium enhancement in isolated noncompaction
      cardiomyopathy.

PMID- 25845743
TI  - Reply: To PMID 25250955.

PMID- 25845745
TI  - Endoplasmic reticulum stress causes autophagy and apoptosis leading to cellular
      redistribution of the autoantigens Ro/Sjogren's syndrome-related antigen A (SSA)
      and La/SSB in salivary gland epithelial cells.
AB  - The aim of this study was to examine the levels of endoplasmic reticulum (ER)
      stress in minor salivary glands, to investigate the interplay between ER stress
      induced autophagy and apoptosis in human salivary gland (HSG) cells and to test
      the effect of ER stress-induced apoptosis on the cellular redistribution of the
      two major Sjogren's syndrome (SS) autoantigens Ro/Sjogren's syndrome-related
      antigen A (SSA) and La/Sjogren's syndrome-related antigen B (SSB). Minor salivary
      gland biopsies from SS patients and sicca controls were examined by
      immunohistochemistry for the expression of 78 kDa glucose-regulated
      protein/binding immunoglobulin protein (GRP78/BiP) as an indicator of unfolded
      protein response (UPR). HSG cells were treated with thapsigargin (TG) and cell
      viability, autophagy and apoptosis were assessed. Immunoblot was applied to
      detect the conversion of LC3I to LC3II and the protein levels of GRP78/BiP and X
      box binding protein-1 (XBP-1). Apoptosis was evaluated by a single-stranded DNA
      enzyme-linked immunosorbent assay (ELISA). Ro/SSA and La/SSB localization was
      visualized using immunofluorescence. GRP78/BiP was expressed by acinar and ductal
      epithelial cells in salivary glands of patients and sicca controls. TG treatment
      induced autophagy, as indicated by enhanced protein expression of LC3II. The
      protein levels of UPR marker XBP-1 were increased after TG treatment, while
      GRP78/BiP levels were decreased. TG treatment resulted in induction of HSG
      apoptosis. Ro/SSA and La/SSB autoantigens were localized predominantly to the
      cytoplasm in resting cells, while they were redistributed to cell membrane and
      blebs in the apoptotic cells. In conclusion, ER stress is activated in minor
      salivary gland epithelial cells from SS patients and controls. ER stress-induced
      apoptosis in HSG cells leads to cell surface and apoptotic blebs relocalization
      of Ro/SSA and La/SSB autoantigens. 

PMID- 25845746
TI  - Differential odor sensitivity in PTSD: Implications for treatment and future
      research.
AB  - BACKGROUND: Given that odors enhance the retrieval of autobiographical memories,
      induce physiological arousal, and trigger trauma-related flashbacks, it is
      reasonable to hypothesize that odors play a significant role in the
      pathophysiology of posttraumatic stress disorder (PTSD). For these reasons, this
      preliminary study sought to examine self-reported, odor-elicited distress in
      PTSD. METHODS: Combat veterans with (N=30) and without (N=22) PTSD and healthy
      controls (HC: N=21), completed an olfactory questionnaire that provided
      information on the hedonic valence of odors as well as their ability to elicit
      distress or relaxation. RESULTS: Two main findings were revealed: Compared to HC,
      CV+PTSD, but not CV-PTSD, reported a higher prevalence of distress to a limited
      number of select odors that included fuel (p=.004), blood (p=.02), gunpowder
      (p=.03), and burning hair (p=.02). In contrast to this increased sensitivity, a
      blunting effect was reported by both groups of veterans compared to HC that
      revealed lower rates of distress and relaxation in response to negative hedonic
      odors (p=.03) and positive hedonic odors (p<.001), respectively. LIMITATIONS: The
      study is limited by its use of retrospective survey methods, whereas future
      investigations would benefit from laboratory measures taken prior, during, and
      after deployment. CONCLUSION: The present findings suggest a complex role of
      olfaction in the biological functions of threat detection. Several theoretical
      models are discussed. One possible explanation for increased sensitivity to
      select odors with decreased sensitivity to other odors is the co-occurrence of
      attentional bias toward threat odors with selective ignoring of distractor odors.
      Working together, these processes may optimize survival.

PMID- 25845747
TI  - Decreased insular connectivity in drug-naive major depressive disorder at rest.
AB  - BACKGROUND: The insula has extensive links to the fronto-limbic circuit and
      associated regions, which is involved in the neurobiology of major depressive
      disorder (MDD). However, few studies are designed to examine the insular
      connectivity in MDD. This study was performed to examine the insular connectivity
      in drug-naive MDD directly by using the insular cortices as seeds. METHODS:
      Functional magnetic resonance imaging data were obtained from 44 drug-naive MDD
      patients and 44 healthy controls at rest. The functional connectivity (FC) method
      was used to analyze the images. RESULTS: Significantly decreased FCs were found
      between the right insula and the left middle frontal gyrus (MFG, orbital part),
      left superior temporal gyrus (STG), right putamen, and right middle occipital
      gyrus (MOG), and between the left insula and the left superior temporal pole and
      right MOG in the patients compared with the controls. There were significantly
      negative correlations between the z values of the left insula-left superior
      temporal pole connectivity and the current episode duration (r=-0.332, p=0.028),
      between the z values of the right insula-left STG connectivity and the episode
      number (r=-0.343, p=0.023), and between the z values of the right insula-left MFG
      (orbital part) connectivity and the Automatic Thoughts Questionnaire scores (r=
      0.359, p=0.017) in the patients. CONCLUSIONS: The findings reveal that depressed
      patients have decreased insular connectivity with the fronto-limbic circuit, hate
      circuit, and visual regions, and suggest that the insula may act as an
      integration center of emotional processing which is disrupted in the depressed
      patients.

PMID- 25845748
TI  - Symptom-specific course trajectories and their determinants in primary care
      patients with Major Depressive Disorder: Evidence for two etiologically distinct
      prototypes.
AB  - BACKGROUND: The course-heterogeneity of Major Depressive Disorder (MDD) hampers
      development of better prognostic models. Although latent class growth analyses
      (LCGA) have been used to explain course-heterogeneity, such analyses have failed
      to also account for symptom-heterogeneity of depressive symptoms. Therefore, the
      aim was to identify more specific data-driven subgroups based on patterns of
      course-trajectories on different depressive symptom domains. METHODS: In primary
      care MDD patients (n=205), the presence of the MDD criterion symptoms was
      determined for each week during a year. Weekly 'mood/cognition' (MC) and
      'somatic' (SOM) scores were computed and parallel processes-LCGA (PP-LCGA) was
      used to identify subgroups based on the course on these domains. The classes'
      associations with baseline predictors and 2-/3-year outcomes were investigated.
      RESULTS: PP-LCGA identified four classes: quick recovery, persisting SOM,
      persisting MC, and persisting SOM+MC (chronic). Persisting SOM was specifically
      predicted by higher baseline somatic symptomatology and somatization, and was
      associated with more somatic depressive symptomatology at long-term follow-up.
      Persisting MC was specifically predicted by higher depressive severity, thinking
      insufficiencies, neuroticism, loneliness and lower self-esteem, and was
      associated with lower mental health related quality of life and more
      mood/cognitive depressive symptomatology at follow-up. LIMITATIONS: The sample
      was small and contained only primary care MDD patients. The weekly depression
      assessments were collected retrospectively at 3-month intervals. CONCLUSIONS: The
      results indicate that there are two specific prototypes of depression,
      characterized by either persisting MC or persisting SOM, which have different
      sets of associated prognostic factors and long-term outcomes, and could have
      different etiological mechanisms.

PMID- 25845749
TI  - Association between HLA-DRB1*0405, -DQB1*0401 and -DQA1*0303 alleles and
      lamotrigine-induced cutaneous adverse drug reactions. A pilot case-control study
      from Japan.
AB  - BACKGROUND: Human leukocyte antigen (HLA) genotypes in lamotrigine -induced (LTG
      induced) cutaneous adverse drug reactions (cADRs) have been described in several
      reports but controversy remains even for a given ethnic group. We attempted to
      clarify a possible association between LTG-induced cADRs and HLA alleles in
      Japanese patients. METHOD: Sixteen subjects, including eight patients with LTG
      induced cADRs and eight LTG-tolerant controls were included in this study. All
      eight patients with LTG-induced cADRs gave positive results in a drug-induced
      lymphocyte stimulation test (DLST) with LTG. We performed HLA-typing for HLA-A, 
      B, -C, -DRB1, -DQA1, -DQB1, -DPA1 and -DPB1, using PCR with sequence-specific
      oligonucleotide probes and multiple analyte profiling (xMAP) technology (Luminex
      System; Luminex Corporation, Austin, TX). We examined differences between allele
      frequencies in our two groups of subjects and the allele frequencies in the
      general Japanese population. RESULTS: The frequencies of HLA-DRB1*0405, and HLA
      DQB1*0401 alleles were higher in our LTG-cADRs patients than the reference
      frequencies in the general Japanese population. We also detected HLA-DQA1*0303
      frequently in our LTG-cADRs patients, but data for this allele in the Japanese
      population was not available. Our observation was presumably due to the linkage
      disequilibrium among the three alleles. The haplotype frequency of HLA-DRB1*0405,
      DQB1*0401 and DQA1*0303 in our LTG-cADRs subjects was also different from the
      corresponding haplotype frequency in the database for the Japanese population and
      the difference was statistically significant. One patient with the HLA-DRB1*0405,
      -DQB1*0401 and DQA1*0303 haplotype was safely re-treated with LTG after results
      of a DLST with LTG ceased to be positive about 4 months after discontinuation of
      LTG. LIMITATIONS: Our analysis included only 16 patients. Associations between
      LTG-induced cADRs and specific HLA loci will have to be confirmed in larger
      studies. CONCLUSIONS: LTG-induced cADRs are associated with HLA-DRB1*0405, 
      DQB1*0401 and -DQA1*0303.

PMID- 25845750
TI  - Systematic review of neurocognition in people with co-occurring alcohol misuse
      and depression.
AB  - BACKGROUND: Alcohol misuse and depression represent two major social and health
      problems globally. These conditions commonly co-occur and both are associated
      with significant cognitive impairment. Despite this, few studies have examined
      the impact on cognitive functioning of co-occurring alcohol misuse and
      depression. This study aims to critically review findings from peer-reviewed
      published articles examining neuropsychological test performance among samples of
      people with co-occurring alcohol misuse and depression. METHOD: A comprehensive
      literature search was conducted, yielding six studies reporting
      neuropsychological profiles of people with co-occurring alcohol misuse and
      depression. Results comparing cognitive functioning of people with this
      comorbidity to those with alcohol misuse alone, depression alone, healthy
      controls and published norms were examined as well as those describing the
      correlation between depressive symptoms and cognitive functioning in people with
      alcohol use disorders. RESULTS: In the majority of instances, the comorbid groups
      did not differ significantly from those with depression only or alcohol misuse
      only, nor from healthy controls or published norms. In the cases where a
      difference in neuropsychological test scores between groups was found, it was not
      consistently identified across studies. However, visual memory was identified in
      two studies as being impaired in comorbid samples and is worthy of inclusion in
      future studies. LIMITATIONS: Due to the small number of included studies and the
      large variation in inclusion criteria as well as differing assessment tools and
      methodologies between studies, the review did not include a quantitative
      synthesis. CONCLUSIONS: Research into cognitive deficits among people with singly
      occurring versus co-occurring alcohol misuse and depression is accumulating.
      Evidence suggests that the neuropsychological performance among samples with this
      comorbidity is generally not severely impaired and is unlikely to preclude
      benefit from treatment.

PMID- 25845751
TI  - Instruments that prospectively predict bipolar disorder - A systematic review.
AB  - BACKGROUND: Identification of earlier stages of Bipolar Disorder (BD), even prior
      to the first manic episode, may help develop interventions to prevent or delay
      the onset of BD. However, reliable and valid instruments are necessary to
      ascertain such earlier stages of BD. The aim of the current review was to
      identify instruments that had predictive validity and utility for BD for use in
      early intervention (EI) settings for the prevention of BD. METHODS: We undertook
      a systematic examination of studies that examined participants without BD I or II
      at baseline and prospectively explored the predictive abilities of instruments
      for BD onset over a period of 6 months or more. The instruments and the studies
      were rated with respect to their relative validity and utility predicting onset
      of BD for prevention or early intervention. Odds ratios and area under the curve
      (AUC) values were derived when not reported. RESULTS: Six studies were included,
      identifying five instruments that examined sub-threshold symptoms, family
      history, temperament and behavioral regulation. Though none of the identified
      instruments had been examined in high-quality replicated studies for predicting
      BD, two instruments, namely the Child Behavioral Checklist - Pediatric BD
      phenotype (CBCL-PBD) and the General Behavioral Inventory - Revised (GBI-R), had
      greater levels of validity and utility. LIMITATION: Non-inclusion of studies and
      instruments that incidentally identified BD on follow-up limited the breadth of
      the review. CONCLUSION: Instruments that test domains such as subthreshold
      symptoms, behavioral regulation, family history, and temperament hold promise in
      predicting BD onset.

PMID- 25845752
TI  - Prevalence of major depressive disorder and socio-demographic correlates: Results
      of a representative household epidemiological survey in Beijing, China.
AB  - BACKGROUND: Major depressive disorder (MDD) is the most prevalent mental disorder
      in the general population and has been associated with socioeconomic factors.
      Beijing has undergone significant socioeconomic changes in last decade, however
      no large-scale community epidemiological surveys of MDD have been conducted in
      Beijing since 2003. AIMS: To determine the prevalence of MDD and its socio
      demographic correlates in a representative household sample of the general
      population in Beijing, China. METHOD: Data were collected from the 2010
      representative household epidemiological survey of mental disorders in Beijing.
      The multistage cluster random sampling method was used to select qualified
      subjects in 18 districts and counties, and then face-to-face interviews were
      administered using the Chinese version of Structured Clinical Interview for DSM
      IV-TR Axis I Disorders-Patient Edition (SCID-I/P) during November 1, 2010 to
      December 31, 2010. RESULTS: 19,874 registered permanent residents were randomly
      identified and 16,032 (response rate=80.7%) completed face-to-face interviews.
      The time-point and life-time prevalence rates of MDD were estimated to be 1.10%
      (95% CI: 0.94-1.26%) and 3.56% (95% CI: 3.27-3.85%) respectively. Significant
      differences were found in sex, age, location of residence, marital status,
      education, employment status, personal/family monthly income, perception of
      family environment and relationship with others, when comparing residents with
      MDD to those without MDD. Those who were female, aged 45 or above, reported low
      family income, or reported an "average" or "poor" family environment were
      associated with a higher risk of MDD. CONCLUSIONS: The prevalence of MDD reported
      in this survey is relatively lower than that in other western countries. Female
      sex, age older than 45, low family income, and poor family environment appear to
      be independent risk factors for MDD.

PMID- 25845753
TI  - Evaluation of adjuvant activity of fractions derived from Agaricus blazei, when
      in association with the recombinant LiHyp1 protein, to protect against visceral
      leishmaniasis.
AB  - The development of effective prophylactic strategies to prevent leishmaniasis has
      become a high priority. No less important than the choice of an antigen, the
      association of an appropriate adjuvant is necessary to achieve a successful
      vaccination, as the majority of the tested antigens contain limited immunogenic
      properties, and need to be supplemented with immune response adjuvants in order
      to boost their immunogenicity. However, few effective adjuvants that can be used
      against leishmaniasis exist on the market today; therefore, it is possible to
      speculate that the research aiming to identify new adjuvants could be considered
      relevant. Recently, Agaricus blazei extracts have proved to be useful in
      enhancing the immune response to DNA vaccines against some diseases. This was
      based on the Th1 adjuvant activity of the polysaccharide-rich fractions from this
      mushroom. In this context, the present study evaluated purified fractions derived
      from Agaricus blazei as Th1 adjuvants through in vitro assays of their immune
      stimulation of spleen cells derived from naive BALB/c mice. Two of the tested six
      fractions (namely F2 and F4) were characterized as polysaccharide-rich fractions,
      and were able to induce high levels of IFN-gamma, and low levels of IL-4 and IL
      10 in the spleen cells. The efficacy of adjuvant action against L. infantum was
      evaluated in BALB/c mice, with these fractions being administered together with a
      recombinant antigen, LiHyp1, which was previously evaluated as a vaccine
      candidate, associated with saponin, against visceral leishmaniasis (VL). The
      associations between LiHyp1/F2 and LiHyp1/F4 were able to induce an in vivo Th1
      response, which was primed by high levels of IFN-gamma, IL-12, and GM-CSF, by low
      levels of IL-4 and IL-10; as well as by a predominance of IgG2a antibodies in the
      vaccinated animals. After infection, the immune profile was maintained, and the
      vaccines proved to be effective against L. infantum. The immune stimulatory
      effects in the BALB/c mice proved to be similar when comparing the F2 and F4
      fractions with a known Th1 adjuvant (saponin), though animals vaccinated with
      saponin did present a slight to moderate inflammatory edema on their hind
      footpads. In conclusion, the F2 and F4 fractions appear to induce a Th1-type
      immune response and, in this context, they could be evaluated in association with
      other protective antigens against Leishmania, as well as in other disease models.

PMID- 25845754
TI  - Prevalence and molecular characterization of Giardia duodenalis isolates from
      dairy cattle in northeast China.
AB  - Giardia duodenalis is an important zoonotic intestinal parasite responsible for
      diarrhea in humans and other animals worldwide. The present study was conducted
      to assess the prevalence of bovine giardiosis and to perform molecular
      characterization of Giardia duodenalis in the northeast of China. A total of 655
      fecal specimens were collected from dairy cattle in 15 farms located in three
      different provinces. G. duodenalis assemblages and subtypes were determined by
      sequence analysis of the triosephosphate isomerase (TPI) gene. As a whole, the G.
      duodenalis infection rate in dairy cattle was 7.9% (52/655), as determined by
      Lugol's iodine staining. Two assemblages were identified, namely, the potentially
      zoonotic assemblage A (n = 1), the livestock-specific assemblage E (n = 50), and
      a mixed infection case of assemblages A and E. Seven distinct subtypes of E
      assemblages were identified and E-XI, E-I and E-III are the major subtypes. Only
      subtype A-I was identified in assemblage A. Findings relevant to assemblage A are
      of public health importance. The results indicated the livestock-specific
      assemblage E is the major genotype and zoonotic assemblage A or B occurs very
      seldomly which is significantly different with previous report in the same area.
      So that determination of genotypes in individual epidemiological setting can make
      important contributions to public health. 

PMID- 25845755
TI  - Subtype-specific influenza A virus antibodies in Canada geese (Branta
      canadensis).
AB  - Historically, surveillance for influenza A viruses (IAVs) in wild birds has
      relied on viral detection assays. This was largely due to poor performance of
      serological assays in wild birds; however, recently developed commercial
      serological assays have improved the ability to detect IAV antibodies in wild
      birds. Serological surveillance for IAV antibodies in Canada geese (Branta
      canadensis) has shown that, despite a low prevalence of virus isolations, Canada
      geese are frequently exposed to IAVs and that exposure increases with latitude,
      which follows virus isolation prevalence patterns observed in dabbling ducks. The
      objectives of this study were to further evaluate IAV antibodies in Canada geese
      using a subtype-specific serological assay to determine if Canada geese are
      exposed to subtypes that commonly circulate in dabbling ducks. We collected serum
      samples from Canada geese in Minnesota, New Jersey, Pennsylvania, and Wisconsin
      and tested for antibodies to IAVs using a blocking ELISA. Positive samples were
      further tested by hemagglutination inhibition for 10 hemagglutinin IAV subtypes
      (H1-H10). Overall, we detected antibodies to NP in 24% (714/2919) of geese.
      Antibodies to H3, H4, H5, and H6 subtypes predominated, with H5 being detected
      most frequently. A decrease in H5 HI antibody prevalence and titers was observed
      from 2009 to 2012. We also detected similar exposure pattern in Canada geese from
      New Jersey, Minnesota, Washington and Wisconsin. Based on the published
      literature, H3, H4, and H6 viruses are the most commonly reported IAVs from
      dabbling ducks. These results indicate that Canada geese also are frequently
      exposed to viruses of the same HA subtypes; however, the high prevalence of
      antibodies to H5 viruses was not expected as H5 IAVs are generally not well
      represented in reported isolates from ducks. 

PMID- 25845756
TI  - Arabidopsis flower development--of protein complexes, targets, and transport.
AB  - Tremendous progress has been achieved over the past 25 years or more of research
      on the molecular mechanisms of floral organ identity, patterning, and
      development. While collections of floral homeotic mutants of Antirrhinum majus
      laid the foundation already at the beginning of the previous century, it was the
      genetic analysis of these mutants in A. majus and Arabidopsis thaliana that led
      to the development of the ABC model of floral organ identity more than 20 years
      ago. This intuitive model kick-started research focused on the genetic mechanisms
      regulating flower development, using mainly A. thaliana as a model plant. In
      recent years, interactions among floral homeotic proteins have been elucidated,
      and their direct and indirect target genes are known to a large extent. Here, we
      provide an overview over the advances in understanding the molecular mechanism
      orchestrating A. thaliana flower development. We focus on floral homeotic protein
      complexes, their target genes, evidence for their transport in floral primordia,
      and how these new results advance our view on the processes downstream of floral
      organ identity, such as organ boundary formation or floral organ patterning.

PMID- 25845757
TI  - Impact of Non-Pulmonary Vein Foci on the Outcome of the Second Session of
      Catheter Ablation for Paroxysmal Atrial Fibrillation.
AB  - BACKGROUND: Paroxysmal atrial fibrillation (AF) is primarily triggered by
      pulmonary veins (PVs). However, non-PV AF foci may also trigger AF. METHODS: We
      examined 207 patients (mean age, 62 +/- 11 years; 166 men) who underwent a second
      catheter ablation (CA) and evaluated the clinical significance of non-PV AF foci
      on the outcomes. RESULTS: Electrical reconnections between the PVs and left
      atrium (LA) were observed in 162 patients (78.3%). Non-PV AF foci were identified
      in 95 patients (45.9%, 60 patients with successfully ablated non-PV AF foci and
      35 with unmappable non-PV AF foci). During a median follow-up period of 22.7
      months, 61 patients (29.5%; 18/112 [16.1%] without non-PV AF foci vs. 20/60
      [33.3%] with successfully ablated non-PV AF foci vs. 23/35 [65.7%] with
      unmappable non-PV AF foci, P < 0.0001) developed AF recurrence; 52 (85.2%)
      developed recurrence within 1 year. The presence of non-PV AF foci was a
      significant clinical predictor of AF recurrence after the second CA; successfully
      ablated non-PV AF foci increased the AF recurrence risk by 2.24 times (95%
      confidence interval [CI], 1.12-4.54; P = 0.02), and unmappable AF foci increased
      this risk by 5.58 times (95% CI, 2.73-11.63; P < 0.0001). CONCLUSION: Nearly half
      of the patients had non-PV AF foci at the second CA session. AF recurred after
      the second CA session in approximately 30%, with most recurrences happening
      within 1 year. The presence of non-PV AF foci significantly increased the AF
      recurrence risk after a second CA. When non-PV AF foci were unmappable, the AF
      recurrence rate was extremely high.

PMID- 25845758
TI  - Expression of ribosome-binding protein 1 correlates with shorter survival in Her
      2 positive breast cancer.
AB  - The aim of this study is to investigate the expression of ribosome-binding
      protein 1 (RRBP1) in invasive breast cancer and to analyze its relationship to
      clinical features and prognosis. RRBP1 expression was studied using real-time
      quantitative PCR and western blotting using pair-matched breast samples and
      immunohistochemical staining using a tissue microarray. Then the correlation
      between RRBP1 expression and clinicopathologic features was analyzed. RRBP1 mRNA
      and protein expression were significantly increased in breast cancer tissues
      compared with normal tissues. The protein level of RRBP1 is proved to be
      positively related to histological grade (P = 0.02), molecular subtype (P =
      0.048) and status of Her-2 (P = 0.026) and P53 (P = 0.015). We performed a grade
      stratified analysis of all patients according to the level of RRBP1 expression
      and found that RRBP1 overexpression highly affected overall survival in patients
      with early-stage (I and II) tumors (P = 0.042). Furthermore, Her-2 positive
      patients with negative RRBP1 expression had longer overall survival rates than
      those with positive RRBP1 expression (P = 0.031). Using multivariate analysis, it
      was determined that lymph node metastasis (LNM, P = 0.002) and RRBP1 expression
      (P = 0.005) were independent prognosis factors for overall survival. RRBP1 is a
      valuable prognostic factor in Her-2-positive breast cancer patients, indicating
      that RRBP1 is a potentially important target for the prediction of prognosis.

PMID- 25845759
TI  - Safety of intravenous thrombolysis for acute ischemic stroke in specific
      conditions.
AB  - INTRODUCTION: Intravenous administration of tissue-type plasminogen activator (IV
      tPA) remains the only approved therapy that may reverse neurological deficit in
      patients with acute ischemic stroke (AIS). During the past 20 years, accumulating
      real-word experience have provided additional information regarding its safety
      and efficacy in various clinical settings that were originally considered as
      contraindications for systemic thrombolysis. AREAS COVERED: In this narrative
      review, we address the safety of intravenous thrombolysis (IVT) in specific
      conditions: dissection of the aortic arch of extracranial and intracranial
      arteries, concomitant presence of unruptured intracranial aneurysms,
      arteriovenous malformations and dural fistulas, co-existing brain tumors as well
      as in conditions mimicking AIS. The review systematically evaluates the safety of
      off-label use of IVT and summarizes data from case reports of uncommon
      complications of systemic thrombolysis administration in the setting of acute
      cerebral ischemia. EXPERT OPINION: The present narrative review summarizing 20
      years of clinical experience with IVT for AIS highlights that many of the current
      guidelines and protocols should be adjusted to accommodate recent data from
      registries and real-world experience underscoring the safety of IVT in numerous
      conditions of AIS that were originally considered as relative or absolute
      contraindications for administration of IV-tPA.

PMID- 25845761
TI  - Similarities of serum anti-ganglioside antibodies in first and third episodes of
      recurrent Guillain-Barre syndrome: case report.

PMID- 25845760
TI  - Triptolide ameliorates colonic fibrosis in an experimental rat model.
AB  - Triptolide is known to exert anti-inflammatory and immunomodulatory activities;
      however, its impact on intestinal fibrosis has not been previously examined.
      Based on our previous studies of the suppressive activity of triptolide on human
      colonic subepithelial myofibroblasts and the therapeutic efficacy of triptolide
      in Crohn's disease, it was hypothesized that triptolide may have beneficial
      effects on intestinal fibrosis. In the present study, colonic fibrosis was
      induced in rats by 6 weekly repeated administration with a low-dose of 2,4,6
      trinitrobenzene sulfonic acid (TNBS) and was then treated with triptolide or PBS
      daily (control) simultaneously. Extracellular matrix (ECM) deposition in the
      colon was examined with image analysis of Masson Trichrome staining. Total
      collagen levels in colonic homogenates were measured by a Sircol assay. Collagen
      Ialpha1 transcripts and collagen I protein were measured ex vivo in the isolated
      colonic subepithelial myofibroblasts by reverse transcription-quantitative
      polymerase chain reaction and immunoblot analysis, respectively. The results
      indicated that triptolide decreased ECM deposition and collagen production in the
      colon, and inhibited collagen Ialpha1 transcripts and collagen I protein
      expression in the isolated subepithelial myofibroblasts of the rats with colonic
      fibrosis. In conclusion, triptolide ameliorates colonic fibrosis in the
      experimental rat model, suggesting triptolide may be a promising compound for
      inflammatory bowel disease treatment.

PMID- 25845762
TI  - Pitfalls in ataxia with ocular motor apraxia type 1: pseudodominant inheritance
      and very late onset.

PMID- 25845763
TI  - An open-label trial in Friedreich ataxia suggests clinical benefit with high-dose
      resveratrol, without effect on frataxin levels.
AB  - Friedreich ataxia (FRDA) is due to a triplet repeat expansion in FXN, resulting
      in deficiency of the mitochondrial protein frataxin. Resveratrol is a naturally
      occurring polyphenol, identified to increase frataxin expression in cellular and
      mouse models of FRDA and has anti-oxidant properties. This open-label, non
      randomized trial evaluated the effect of two different doses of resveratrol on
      peripheral blood mononuclear cell (PBMC) frataxin levels over a 12-week period in
      individuals with FRDA. Secondary outcome measures included PMBC FXN mRNA,
      oxidative stress markers, and clinical measures of disease severity. Safety and
      tolerability were studied. Twenty-four participants completed the study; 12
      received low-dose resveratrol (1 g daily) and 12 high-dose resveratrol (5 g
      daily). PBMC frataxin levels did not change in either dosage group [low-dose
      group change: 0.08 pg/MUg protein (95% CI -0.05, 0.21, p = 0.21); high-dose group
      change: 0.03 pg/MUg protein (95% CI -0.10, 0.15, p = 0.62)]. Improvement in
      neurologic function was evident in the high-dose group [change in Friedreich
      Ataxia Rating Scale -3.4 points, 95% CI (-6.6, -0.3), p = 0.036], but not the low
      dose group. Significant improvements in audiologic and speech measures, and in
      the oxidative stress marker plasma F2-isoprostane were demonstrated in the high
      dose group only. There were no improvements in cardiac measures or patient
      reported outcome measures. No serious adverse events were recorded.
      Gastrointestinal side-effects were a common, dose-related adverse event. This
      open-label study shows no effect of resveratrol on frataxin levels in FRDA, but
      suggests that independent positive clinical and biologic effects of high-dose
      resveratrol may exist. Further assessment of efficacy is warranted in a
      randomized placebo-controlled trial.

PMID- 25845764
TI  - Dissociated lower limb muscle involvement in amyotrophic lateral sclerosis.
AB  - It has been suggested that corticomotoneuronal drive to ankle dorsiflexors is
      greater than to ankle plantar flexor muscles, despite the finding that plantar
      flexors are no less active than TA during walking and standing. The present study
      was undertaken to determine whether there was differential involvement of distal
      lower limb muscles in amyotrophic lateral sclerosis (ALS), to elucidate
      pathophysiological mechanisms of selective muscle involvement. Prospective
      studies were undertaken in 52 ALS patients, including clinical assessment,
      disease staging (revised ALS functional rating scale), Medical Research Council
      sum score, and a scale of upper motor neurone (UMN) dysfunction. Motor unit
      number estimates (MUNE) and compound muscle action potentials (CMAP) from ankle
      dorsiflexors and plantar flexors were used to provide objective measures. A novel
      'split leg index' was calculated as follows: SLI = CMAPDF / CMAPPF. In ALS, there
      was significantly greater reduction of MUNE and CMAP amplitude recorded from
      plantar flexors when compared to dorsiflexors, suggesting preferential
      involvement of plantar flexor muscles, underpinning a 'split leg' appearance. The
      SLI correlated with clinical plantar flexor strength (R= -0.56, p < 0.001). In no
      patient did the SLI suggest preferential dorsiflexor involvement. In subgroup
      analyses, mean SLI was greatest in lower limb-onset ALS. In conclusion, the
      present study has established dissociated involvement of muscles acting around
      the ankle in ALS. We suggest this reflects underlying differences in cortical,
      descending or local spinal modulation of these muscles.

PMID- 25845765
TI  - Significance of the hot-cross bun sign on T2*-weighted MRI for the diagnosis of
      multiple system atrophy.
AB  - Although the sensitive detection of putaminal iron deposition by T2*-weighted
      imaging (T2*-WI) is of diagnostic value for multiple system atrophy (MSA), the
      diagnostic significance of the pontine hot-cross bun (HCB) sign with increased
      ferritin-bound iron in the background remains unknown. We retrospectively
      evaluated the cases of 33 patients with cerebellar-form MSA (MSA-C) and 21 with
      MSA of the parkinsonian form (MSA-P) who underwent an MRI study with a 1.5-T
      system. Visualization of the HCB sign, posterior putaminal hypointensity and
      putaminal hyperintense rim on T2*-WI was assessed by two neurologists
      independently using an established visual grade, and were compared with those on
      T2-weighted imaging (T2-WI). The visual grade of pontine and putaminal signal
      changes was separately assessed for probable MSA (advanced stage) and possible
      MSA (early stage). T2*-WI demonstrated significantly higher grades of HCB sign
      than T2-WI (probable MSA-C, n = 27, p < 0.001; possible MSA-C, n = 6, p < 0.05;
      probable MSA-P, n = 13, p < 0.01). The visual grade of the HCB sign on T2*-WI in
      the possible MSA-C patients was comparable to that in the probable MSA-C
      patients. Although the HCB sign in MSA-P was of lower visual grade than in MSA-C
      even on T2*-WI, some patients showed evolution of the HCB sign preceding the
      appearance of the putaminal changes. These findings suggest that T2*-WI is of
      extreme value for detecting the HCB sign, which is often cited as a hallmark of
      MSA. The appearance of the HCB sign on T2*-WI might not only support but also
      improve the diagnosis of MSA.

PMID- 25845766
TI  - Relationship between pituitary stalk (PS) visibility and the severity of hormone
      deficiencies: PS interruption syndrome revisited.
AB  - CONTEXT: Pituitary stalk interruption syndrome (PSIS) is a rare cause of combined
      pituitary hormone deficiency characterized by a triad shown in pituitary imaging,
      yet it has never been evaluated due to the visibility of pituitary stalk (PS) in
      imaging findings. OBJECTIVE: The major objective of the study was to
      systematically describe the disease including clinical presentations, imaging
      findings and to estimate the severity of anterior pituitary hormone deficiency
      based on the visibility of the PS. METHODS: This was a retrospective study
      including 74 adult patients with PSIS in Shanghai Clinical Center for Endocrine
      and Metabolic Diseases between January 2010 and June 2014. Sixty had invisible PS
      according to the findings on MRI, while the rest had a thin or intersected PS.
      Basic characteristics and hormonal status were compared. RESULTS: Of the 74
      patients with PSIS, age at diagnosis was 25 (22-28) years. Absent pubertal
      development (97.3%) was the most common presenting symptom, followed by short
      stature. Insulin tolerance test (ITT) and gonadotrophin-releasing hormone (GnRH)
      stimulation test were used to evaluate the function of anterior pituitary. The
      prevalence of isolated deficiency in growth hormone (GH), gonadotrophins,
      corticotrophin and thyrotrophin were 100%, 97.2%, 88.2% and 70.3%, respectively.
      Although the ratio of each deficiency did not vary between patients with
      invisible PS and with visible PS, panhypopituitarism occurred significantly more
      frequent in patients with invisible PS. Patients with invisible PS had
      significantly lower levels of luteinizing hormone (LH), follicle stimulation
      hormone (FSH) and hormones from targeted glands including morning cortisol, 24-h
      urine free cortisol, free triiodothyronine (FT3), free thyroxine (FT4) and
      testosterone (T) in male than patients with visible PS. Moreover, patients with
      invisible PS had lower peak LH and FSH in GnRH stimulation test, and higher peak
      cortisol in ITT while peak GH remained unchanged between two groups. CONCLUSIONS:
      The prevalence of multiple anterior pituitary hormone deficiency was high in
      adult patients with PSIS. And more importantly, we found the visibility of PS
      shown on MRI might be an indication of the severity of PSIS.

PMID- 25845767
TI  - Biocompatibility assessment of haemodialysis membrane materials by proteomic
      investigations.
AB  - The exposure of blood to an artificial surface such as the haemodialysis membrane
      results in the nearly instantaneous deposition of a layer of plasma proteins. The
      composition of the protein layer profoundly influences all subsequent events, and
      to a large extent determines the biocompatibility of the biomaterial. In the
      present study, we examine the protein adsorption capacity and coagulation
      profiles of the polysulfone-based helixone material in comparison to cellulose
      triacetate. A differential profiling investigation using shotgun proteomics data
      independent analysis was applied to eluates obtained with each membrane after a
      dialysis session, in order to assess the function of desorbed proteins.
      Functional classification and network analysis performed using bioinformatics
      tools shed light on the involvement of adsorbed proteins into important molecular
      processes, such as lipid transport and metabolism, cell growth differentiation
      and communication, and the coagulation cascade. The collected evidence was
      further validated by targeted mass spectrometry using selected reaction
      monitoring on proteotypic transitions of key protein effectors, confirming the
      different panels of adsorbed protein on each membrane. The coagulation profile
      during haemodialysis of patients under polysulfone-based helixone filter
      cartridges was also assessed showing a slightly higher platelet activation
      profile after the dialysis session. The overall collected evidence highlights a
      modulation of the coagulation biological pathway during haemodialysis, which is
      largely influenced by the biomaterial used. 

PMID- 25845768
TI  - Efficacy and safety of empagliflozin monotherapy for 52 weeks in Japanese
      patients with type 2 diabetes: a randomized, double-blind, parallel-group study.
AB  - INTRODUCTION: The aim of this randomized, double-blind, parallel-group study was
      to investigate the safety and efficacy of empagliflozin monotherapy for 52 weeks
      in Japanese patients with type 2 diabetes (T2DM). METHODS: In a 12-week dose
      finding period, patients [N = 547; mean baseline glycosylated hemoglobin (HbA1c)
      7.92-8.02%] received empagliflozin (5, 10, 25, or 50 mg) or placebo. In a 40-week
      extension period, patients on empagliflozin 10 or 25 mg continued the same
      treatment and patients on other doses were reallocated to empagliflozin 10 or 25
      mg. Outcomes at week 52 included changes from baseline in HbA1c, fasting plasma
      glucose (FPG), weight and blood pressure (BP) in patients who received
      empagliflozin 10 or 25 mg in both the initial 12 weeks and the extension and
      safety in patients treated with >=1 dose of empagliflozin 10 or 25 mg. RESULTS:
      Adjusted mean +/- SE changes in HbA1c from baseline at week 52 were -0.67 +/-
      0.09% and -0.86 +/- 0.09%, in FPG were -24.7 +/- 3.2 mg/dL and -31.3 +/- 3.4
      mg/dL, and in body weight were -3.1 +/- 0.4 kg and -3.1 +/- 0.4 kg, with
      empagliflozin 10 and 25 mg, respectively. Both doses reduced systolic and
      diastolic BP. Adverse events were reported in 70.8% and 66.8% of patients on
      empagliflozin 10 and 25 mg, respectively. Confirmed hypoglycemic adverse events
      (plasma glucose <=70 mg/dL and/or requiring assistance) were reported in one
      patient per group. CONCLUSION: Empagliflozin monotherapy for 52 weeks led to
      sustained reductions in HbA1c, FPG, weight and BP and was well tolerated in
      Japanese patients with T2DM. FUNDING: Boehringer Ingelheim and Eli Lilly and
      Company.

PMID- 25845769
TI  - Asthma control: the right inhaler for the right patient.
AB  - Inhaled therapy is the cornerstone of asthma management in that it optimizes the
      delivery of the medication to the site of action. The effectiveness of inhaled
      therapy is affected by the correct choice of the device and proper inhalation
      technique. In fact, this influences the drug delivery and distribution along the
      bronchial tree, including the most peripheral airways. In this context,
      accumulating evidence supports the contribution of small airways in asthma, and
      these have become an important target of treatment. In reality, the "ideal
      inhaler" does not exist, and not all inhalers are the same. Advances in
      technology has highlighted these differences, and have led to the design of new
      devices and the development of formulations characterized by extrafine particles
      that facilitate the distribution and deposition of the drug particles along the
      respiratory tract. In addition, efforts have been made to implement adherence to
      chronic treatment, which translates into clinical benefit. Taken together, the
      optimal control of asthma depends on the drug that is selected, the device that
      is employed and the removal of factors that reduce patient's adherence to
      therapy. 

PMID- 25845771
TI  - Spray-dried amikacin sulphate powder for inhalation in cystic fibrosis patients:
      The role of ethanol in particle formation.
AB  - A Central Composite Design (CCD) was applied in order to identify positive
      combinations of the production parameters of amikacin sulphate spray-dried
      powders for inhalation, with the intent to expand the experimental space defined
      in a previous half-fractional factorial design. Three factors, namely drying
      temperature, feed rate and ethanol proportion, have been selected out of the
      initial five. In addition, the levels of these factors were increased from two to
      three and their effect on amikacin respirability was evaluated. In particular,
      focus was given on the role of ethanol presence on the formation of the
      microparticles for inhalation. The overall outcome of the CCD was that amikacin
      respirability was not substantially improved, as the optimum region coincided
      with areas already explored with the fractional factorial design. However,
      expanding the design space towards smaller ethanol levels, including its complete
      absence, revealed the crucial role of this solvent on the morphology of the
      produced particles. Peclet number and drug solubility in the spraying solution
      helped to understand the formation mechanism of these amikacin sulphate spray
      dried particles. 

PMID- 25845770
TI  - Molecular dynamics simulations of large macromolecular complexes.
AB  - Connecting dynamics to structural data from diverse experimental sources,
      molecular dynamics simulations permit the exploration of biological phenomena in
      unparalleled detail. Advances in simulations are moving the atomic resolution
      descriptions of biological systems into the million-to-billion atom regime, in
      which numerous cell functions reside. In this opinion, we review the progress,
      driven by large-scale molecular dynamics simulations, in the study of viruses,
      ribosomes, bioenergetic systems, and other diverse applications. These examples
      highlight the utility of molecular dynamics simulations in the critical task of
      relating atomic detail to the function of supramolecular complexes, a task that
      cannot be achieved by smaller-scale simulations or existing experimental
      approaches alone. 

PMID- 25845773
TI  - Molecular functionalization of silicene/Ag(111) by covalent bonds: a DFT study.
AB  - Among the 2D crystals, silicene, which forms sp(2)-sp(3) bonds, is expected to
      present a higher reactivity than graphene, characterized by sp(2) bonds only.
      However, silicene functionalization, in particular with organic molecules,
      remains an open question. By means of density functional theory, we study the
      adsorption of benzene, a model organic molecule, on (3 * 3) silicene on the (4 *
      4) Ag(111) surface. Our calculations show that the dispersion interactions must
      be taken into account in order to describe this system properly. The adsorption
      energy is calculated by means of the semi-empirical dispersion-corrected density
      functional theory (DFT-D2) and the optB86b-vdW density functional. The charge
      density and electron localization function maps indicate that the molecule is
      chemisorbed on the silicene surface by means of two Si-C covalent bonds. In
      agreement with charge density difference calculations, two C-C double bonds are
      formed in the benzene molecule, which adopts a butterfly configuration. The
      silicene lattice is slightly deformed upon benzene adsorption, but the Si-Si
      distance remains the same as in bare silicene/Ag(111). Bader analysis shows a
      charge transfer from top Si atoms to both molecules and Ag substrates. Finally,
      we show that the covalent functionalization of silicene is possible. 

PMID- 25845772
TI  - Synergetic skin targeting effect of hydroxypropyl-beta-cyclodextrin combined with
      microemulsion for ketoconazole.
AB  - The objective was to develop a ternary skin targeting system for ketoconazole
      (KET) using a combined strategy of microemulsion (ME) and cyclodextrin (HP-beta
      CD), i.e., KET-CD-ME, which exploits both virtues of cyclodextrin complex and ME
      to obtain the synergetic effect. KET-CD-ME was formulated using Labrafil M 1944
      CS as oil phase, Solutol HS 15 as surfactant, Transcutol P as cosurfactant, and
      HP-beta-CD solution as aqueous phase. The formulation of KET-CD-ME was optimized
      and the optimal formulation was characterized in terms of particle size, size
      distribution, pH value, and viscosity. Long term stability experiment showed that
      HP-beta-CD could increase the physical stability of ternary system and KET
      chemical stability. Percutaneous permeation of KET from KET-CD-ME in vitro
      through rat skin was investigated in comparison with KET microemulsion (KET-ME),
      KET HP-beta-CD inclusion solution (KET-CD), KET aqueous suspension, and
      commercial KET cream; the results showed that the combination of ME with HP-beta
      CD exhibited significantly synergistic effect on KET deposition within the skin
      (29.38 +/- 1.79 MUg/cm(2)) and a slightly synergistic effect on KET penetration
      through the skin (11.3 MUg/cm(2)/h). The enhancement of the combination on skin
      deposition was further visualized by confocal laser scanning microscope (CLSM).
      In vitro sensitivity against Candida parapsilosis test indicated that KET-CD-ME
      enhanced KET antifungal activity mainly owing to the solubilization of HP-beta-CD
      on KET in the ternary system. Moreover, the interactions between HP-beta-CD and
      KET in the ternary system were elucidated through microScale thermophoresis (MST)
      and 2D (1)H NMR spectroscopy. The profiles from MST confirmed the host-guest
      interactions of HP-beta-CD with KET in the ternary system and a deep insight into
      the interactions between KET and HP-beta-CD were obtained by means of 2D (1)H NMR
      spectroscopy. The results indicate that the ternary system of ME combination with
      HP-beta-CD may be a promising approach for skin targeting delivery of KET.

PMID- 25845774
TI  - Dementia: turning fine aspirations into measurable progress.

PMID- 25845775
TI  - 1 year on--lessons from the Ebola outbreak for WHO.

PMID- 25845776
TI  - Perinatal mental health--towards a robust system of care.

PMID- 25845777
TI  - A new social contract for medical innovation.

PMID- 25845778
TI  - The outlook for public spending on the National Health Service.

PMID- 25845780
TI  - Republicans' bills target science at US environment agency.

PMID- 25845781
TI  - Sheena McCormack: helping to prepare the world for PrEP.

PMID- 25845782
TI  - Political roots of the struggle for health justice in Latin America.

PMID- 25845783
TI  - Wayne Jay Katon.

PMID- 25845784
TI  - GBD 2013 and HIV incidence in high income countries.

PMID- 25845785
TI  - What are affordable vaccines?

PMID- 25845786
TI  - Diagnosis of reversible causes of coma.

PMID- 25845787
TI  - Diagnosis of reversible causes of coma.

PMID- 25845788
TI  - Diagnosis of reversible causes of coma - Authors' reply.

PMID- 25845789
TI  - Diagnosis of reversible causes of coma.

PMID- 25845790
TI  - Effects of intensive glycaemic control on ischaemic heart disease - Authors'
      reply.

PMID- 25845791
TI  - Effects of intensive glycaemic control on ischaemic heart disease.

PMID- 25845792
TI  - Alcohol taxation and premature mortality in Europe.

PMID- 25845794
TI  - Department of Error.

PMID- 25845793
TI  - Cancer and cardiovascular disease: more tightly linked than by chance.

PMID- 25845795
TI  - Integrity and the European Society of Cardiology--reply.

PMID- 25845796
TI  - A pregnant woman with acute cardiorespiratory failure: dengue myocarditis.

PMID- 25845797
TI  - A pulmonary tumor-like mass resolving with antibiotics.

PMID- 25845798
TI  - Tubulin inhibitor identification by bioactive conformation alignment
      pharmacophore-guided virtual screening.
AB  - Microtubules are important cellular component that are critical for proper
      cellular function. Microtubules are synthesized by polymerization of alphabeta
      tubulin heterodimers called protofilaments. Microtubule dynamics facilitate
      proper cell division during mitosis. Disruption of microtubule dynamics by small
      molecule agents inhibits mitosis, resulting in apoptotic cell death and
      preventing cell cycle progression. To identify a novel small molecule that binds
      the alphabeta tubulin interface to affect microtubule dynamics, we developed a
      bioactive conformation alignment pharmacophore (BCAP) model to screen tubulin
      inhibitors from a huge database. The application of BCAP model generated based on
      the known alphabeta-tubulin interface binders enabled us to identify several
      small-molecules that cause apoptosis in human promyelocytic leukemia (HL-60)
      cells. Virtual screening combined with an in vitro assay yielded 15 cytotoxic
      molecules. In particular, ethyl 2-(4-(5-methyl-3-nitro-1H-pyrazol-1
      yl)butanamido)-4-phenylthiophene-3-carboxylate (H05) inhibited tubulin
      polymerization with an IC50 of 17.6 MUm concentration. The virtual screening
      results suggest that the application of an unbiased BCAP pharmacophore greatly
      eliminates unlikely compounds from a huge database and maximizes screening
      success. From the limited compounds tested in the tubulin polymerization
      inhibitor (TPI) assay, compound H05 was discovered as a tubulin inhibitor. This
      compound requires further structure activity optimization to identify additional
      potent inhibitors from the same class of molecules. 

PMID- 25845799
TI  - Reliability and sensitivity of a simple isometric posterior lower limb muscle
      test in professional football players.
AB  - This study aimed (1) to determine the reliability of a simple and quick test to
      assess isometric posterior lower limb muscle force in professional football
      players and (2) verify its sensitivity to detect reductions in force following a
      competitive match. Twenty-nine professional football players performed a 3-s
      maximal isometric contraction of the posterior lower limb muscles for both legs
      with players lying supine. Both legs were tested using a knee angle of 90 degrees
      and 30 degrees  measured on a force plate. Players were tested twice with one
      week between sessions to verify reliability. Sensitivity was tested following a
      full competitive football match. The test showed high reliability for dominant
      leg at 90 degrees  (CV = 4.3%, ICC = 0.95, ES = 0.15), non-dominant leg at 90
      degrees  (CV = 5.4%, ICC = 0.95, ES = 0.14), and non-dominant leg at 30 degrees 
      (CV = 4.8%, ICC = 0.93, ES = 0.30) and good reliability for dominant leg at 30
      degrees  (CV = 6.3%, ICC = 0.86, ES = 0.05). The measure was sensitive enough to
      detect reductions in force for dominant leg at 90 degrees  (P = 0.0006, ES > 1),
      non-dominant leg at 90 degrees  (P = 0.0142, ES = 1), and non-dominant leg at 30
      degrees  (P = 0.0064, ES > 1) and for dominant leg at 30 degrees  (P = 0.0016, ES
      > 1). In conclusion, the present test represents a useful and practical field
      tool to determine the magnitude of match-induced fatigue of the posterior lower
      limb muscles and potentially to track their recovery. 

PMID- 25845800
TI  - Molecular features of the sortase enzyme family.
AB  - Bacteria possess complex and varying cell walls with many surface exposed
      proteins. Sortases are responsible for the covalent attachment of specific
      proteins to the peptidoglycan of the cell wall of Gram-positive bacteria. Sortase
      A of Staphylococcus aureus, which is seen as the archetypal sortase, has been
      shown to be essential for pathogenesis and has therefore received much attention
      as a potential target for novel therapeutics. Being widely present in Gram
      positive bacteria, it is likely that other Gram-positive pathogens also require
      sortases for their pathogenesis. Sortases have also been shown to be of
      significant use in a range of industrial applications. We review current
      knowledge of the sortase family in terms of their structures, functions and
      mechanisms and summarize work towards their use as antibacterial targets and
      microbiological tools.

PMID- 25845801
TI  - Progressive outer retinal necrosis in a renal transplant recipient: a rare
      treatment success.
AB  - Renal transplant recipients (RTRs) are subject to a variety of opportunistic
      infections. We present a rare case of varicella zoster virus-derived progressive
      outer retinal necrosis in an RTR, who presented with painless visual blurring.
      This clinical entity heralds an extremely poor visual prognosis and is an
      important condition to consider in any immunocompromised host. Early diagnosis by
      aqueous fluid sampling and immediate institution of combined systemic and
      intravitreal antiviral therapy was successful in this individual. 

PMID- 25845802
TI  - Multiscale Modeling of Gene-Behavior Associations in an Artificial Neural Network
      Model of Cognitive Development.
AB  - In the multidisciplinary field of developmental cognitive neuroscience,
      statistical associations between levels of description play an increasingly
      important role. One example of such associations is the observation of
      correlations between relatively common gene variants and individual differences
      in behavior. It is perhaps surprising that such associations can be detected
      despite the remoteness of these levels of description, and the fact that behavior
      is the outcome of an extended developmental process involving interaction of the
      whole organism with a variable environment. Given that they have been detected,
      how do such associations inform cognitive-level theories? To investigate this
      question, we employed a multiscale computational model of development, using a
      sample domain drawn from the field of language acquisition. The model comprised
      an artificial neural network model of past-tense acquisition trained using the
      backpropagation learning algorithm, extended to incorporate population modeling
      and genetic algorithms. It included five levels of description-four internal:
      genetic, network, neurocomputation, behavior; and one external: environment.
      Since the mechanistic assumptions of the model were known and its operation was
      relatively transparent, we could evaluate whether cross-level associations gave
      an accurate picture of causal processes. We established that associations could
      be detected between artificial genes and behavioral variation, even under
      polygenic assumptions of a many-to-one relationship between genes and
      neurocomputational parameters, and when an experience-dependent developmental
      process interceded between the action of genes and the emergence of behavior. We
      evaluated these associations with respect to their specificity (to different
      behaviors, to function vs. structure), to their developmental stability, and to
      their replicability, as well as considering issues of missing heritability and
      gene-environment interactions. We argue that gene-behavior associations can
      inform cognitive theory with respect to effect size, specificity, and timing. The
      model demonstrates a means by which researchers can undertake multiscale modeling
      with respect to cognition and develop highly specific and complex hypotheses
      across multiple levels of description. 

PMID- 25845803
TI  - Comments on the paper "Medicolegal implications of accuracy of GP referral
      letters to specialist breast clinic".

PMID- 25845804
TI  - Using Animals in Nursing Research: Bridging Gaps Between Bench, Bedside, and
      Practice.

PMID- 25845805
TI  - Review and Synthesize Completed Research Through Systematic Review.
AB  - The evidence-based health care movement has generated new opportunity for
      scholars to generate synthesized sources of evidence. Systematic reviews are
      rigorous forms of synthesized evidence that scholars can conduct if they have
      requisite skills, time, and access to excellent library resources. Systematic
      reviews play an important role in synthesizing what is known and unknown about a
      particular health issue. Thus, they have a synergistic relationship with primary
      research. They can both inform clinical decisions when the evidence is adequate
      and identify gaps in knowledge to inform research priorities. Systematic reviews
      can be conducted of quantitative and qualitative evidence to answer many types of
      questions. They all share characteristics of rigor that arise from a priori
      protocol development, transparency, exhaustive searching, dual independent
      reviewers who critically appraise studies using standardized tools, rigor in
      synthesis, and peer review at multiple stages in the conduct and reporting of the
      systematic review. 

PMID- 25845806
TI  - Arterial blood pressure but not serum albumin concentration correlates with ADC
      ratio values in pediatric posterior reversible encephalopathy syndrome.
AB  - INTRODUCTION: Posterior reversible encephalopathy syndrome (PRES) is a clinical
      radiological entity affecting both adults and children characterized by
      neurotoxicity often in setting of hypertension coupled with distinct brain
      magnetic resonance imaging features. Decreased serum albumin level has been
      suggested to correlate with the presence of vasogenic brain edema in adult PRES.
      Serum albumin has thus been hypothesized to protect against neurotoxicity in PRES
      by reducing vasogenic brain edema through its role in maintaining plasma osmotic
      pressure and endothelial integrity. The purpose of our study was to investigate
      if such correlation between decreased serum albumin level and PRES-related
      vasogenic edema could be found in children. METHODS: We conducted a retrospective
      study of 25 pediatric patients diagnosed with PRES. Underlying clinical
      conditions, presenting symptoms, blood pressures, and serum albumin levels at
      onset of symptoms were collected. Brain MR imaging studies were reviewed. We used
      a quantitative method to evaluate the degree of vasogenic edema by measuring
      apparent diffusion coefficient (ADC) values of the T2-FLAIR hyperintense brain
      lesions. RESULTS: No significant correlation was found between serum albumin
      level and degree of PRES-related vasogenic edema. A significant correlation was
      found between elevated blood pressure and degree of vasogenic edema in the
      temporal lobes (p = 0.02 and 0.04, respectively) but not in the other cerebral
      lobes or cerebellum. CONCLUSIONS: Our initial results suggest blood pressure, not
      serum albumin level, as a main biomarker for brain edema in children with PRES.
      Thus, our study does not suggest a protective role of serum albumin against PRES
      related neurotoxicity in children.

PMID- 25845807
TI  - Conventional 3T brain MRI and diffusion tensor imaging in the diagnostic workup
      of early stage parkinsonism.
AB  - INTRODUCTION: The aim of this study is to evaluate whether the diagnostic
      accuracy of 3 T brain MRI is improved by region of interest (ROI) measures of
      diffusion tensor imaging (DTI), to differentiate between neurodegenerative
      atypical parkinsonism (AP) and Parkinson's disease (PD) in early stage
      parkinsonism. METHODS: We performed a prospective observational cohort study of
      60 patients presenting with early stage parkinsonism and initial uncertain
      diagnosis. At baseline, patients underwent a 3 T brain MRI including DTI. After
      clinical follow-up (mean 28.3 months), diagnoses could be made in 49 patients (30
      PD and 19 AP). Conventional brain MRI was evaluated for regions of atrophy and
      signal intensity changes. Tract-based spatial statistics and ROI analyses of DTI
      were performed to analyze group differences in mean diffusivity (MD) and
      fractional anisotropy (FA), and diagnostic thresholds were determined. Diagnostic
      accuracy of conventional brain MRI and DTI was assessed with the receiver
      operating characteristic (ROC). RESULTS: Significantly higher MD of the centrum
      semiovale, body corpus callosum, putamen, external capsule, midbrain, superior
      cerebellum, and superior cerebellar peduncles was found in AP. Significantly
      increased MD of the putamen was found in multiple system atrophy-parkinsonian
      form (MSA-P) and increased MD in the midbrain and superior cerebellar peduncles
      in progressive supranuclear palsy (PSP). The diagnostic accuracy of brain MRI to
      identify AP as a group was not improved by ROI measures of MD, though the
      diagnostic accuracy to identify MSA-P was slightly increased (AUC 0.82 to 0.85).
      CONCLUSION: The diagnostic accuracy of brain MRI to identify AP as a group was
      not improved by the current analysis approach to DTI, though DTI measures could
      be of added value to identify AP subgroups.

PMID- 25845808
TI  - Association between idiopathic intracranial hypertension and sigmoid sinus
      dehiscence/diverticulum with pulsatile tinnitus: a retrospective imaging study.
AB  - INTRODUCTION: The mechanism of occurrence of sigmoid sinus
      dehiscence/diverticulum (SSDD) in pulsatile tinnitus (PT) patients remains under
      debate. Its association with idiopathic intracranial hypertension (IIH) lacks
      evidence, which is important for therapeutic planning and improving the clinical
      outcome. This study aimed to evaluate the association between SSDD and IIH by
      comparing the prevalence of several established imaging features of IIH between
      PT patients with SSDD and healthy volunteers. METHODS: Thirty-three unilateral PT
      patients with SSDD identified on CT images and 33 age- and sex-matched healthy
      volunteers underwent T1-weighted volumetric magnetic resonance imaging (MRI). The
      optic nerve, pituitary gland, transverse sinus, and ventricles were assessed. The
      prevalence of established IIH imaging features was compared between the two
      groups. Furthermore, the PT patients were divided into two subgroups: PT patients
      with dehiscence only and PT patients with diverticulum. The same statistical
      analysis was performed on each pathophysiologic entity respectively. RESULTS: The
      PT patients with SSDD showed a significantly higher prevalence of empty sella (P
      < 0.001), flattened posterior sclera (P = 0.001), vertical tortuosity of the
      optic nerve (P = 0.001), protrusion of the optic nerve (P = 0.006), transverse
      sinus stenosis (P = 0.011), and distension of the optic nerve sheath (P = 0.000).
      There were no significant differences between the PT and control groups in the
      maximum widths of the third and fourth ventricles and the lateral ventricle size.
      In contrast to controls, the imaging findings persisted in both of
      pathophysiologic entities, except for transverse sinus stenosis. CONCLUSIONS:
      Several IIH imaging features occur more frequently in PT patients with SSDD than
      in healthy individuals, which suggests a potential correlation between SSDD with
      PT and IIH.

PMID- 25845809
TI  - Human cerebral blood volume measurements using dynamic contrast enhancement in
      comparison to dynamic susceptibility contrast MRI.
AB  - INTRODUCTION: Cerebral blood volume (CBV) is an important parameter for the
      assessment of brain tumors, usually obtained using dynamic susceptibility
      contrast (DSC) MRI. However, this method often suffers from low spatial
      resolution and high sensitivity to susceptibility artifacts and usually does not
      take into account the effect of tissue permeability. The plasma volume (vp) can
      also be extracted from dynamic contrast enhancement (DCE) MRI. The aim of this
      study was to investigate whether DCE can be used for the measurement of cerebral
      blood volume in place of DSC for the assessment of patients with brain tumors.
      METHODS: Twenty-eight subjects (17 healthy subjects and 11 patients with
      glioblastoma) were scanned using DCE and DSC. vp and CBV values were measured and
      compared in different brain components in healthy subjects and in the tumor area
      in patients. RESULTS: Significant high correlations were detected between vp and
      CBV in healthy subjects in the different brain components; white matter, gray
      matter, and arteries, correlating with the known increased tissue vascularity,
      and within the tumor area in patients. CONCLUSION: This work proposes the use of
      DCE as an alternative method to DSC for the assessment of blood volume, given the
      advantages of its higher spatial resolution, its lower sensitivity to
      susceptibility artifacts, and its ability to provide additional information
      regarding tissue permeability.

PMID- 25845810
TI  - Intensity of prolactinoma on T2-weighted magnetic resonance imaging: towards
      another gender difference.
AB  - INTRODUCTION: Clinical presentations of prolactinomas are quite different between
      genders. In comparison with women's prolactinoma, those in men showed
      predominance of large tumors with high prolactin (PRL) levels. This preponderance
      could be attributed to a greater proliferative potential of the tumors.
      Differences in magnetic resonance imaging (MRI) signal at diagnosis have not been
      yet clearly evaluated. METHODS: We conduct a retrospective study comparing MRI
      signal intensity (SI) on T2-weighted images (T2-WI) between 41 men and 41 women
      to investigate whether or not men prolactinoma present specific features.
      RESULTS: In addition to the size of the adenoma and PRL levels (P < 0001),
      prolactinomas in men also exhibit differences from those in women in signal on T2
      WI on MRI (P < 0001). Women's prolactinomas are mostly of high SI on T2-WI while
      men's prolactinomas exhibit a more heterogeneous pattern of SI on T2-WI.
      Prolactinomas presenting with low SI on T2-WI are almost exclusively encountered
      in men. CONCLUSIONS: Presence of T2-WI hypointensities in pituitary adenoma can
      be predictive of a different subtype of prolactinoma almost encountered in men
      and possibly translate the presence of spherical amyloid deposits, in agreement
      with the literature.

PMID- 25845811
TI  - Extracranial vertebral artery dissection in children: natural history and
      management.
AB  - INTRODUCTION: The objective of this study is to describe clinical and imaging
      presentation and outcome in extracranial vertebral artery dissection. METHODS:
      Single-centre retrospective study over a 14-year period included 20 consecutive
      patients under the age of 16 years with extracranial vertebral artery dissection.
      The diagnosis was based on vascular imaging performed at the acute phase and
      clinical symptoms. RESULTS: A male predominance was observed (sex ratio 9/1). The
      first symptoms consisted of headache (45%), neck pain (15%), nausea (30%) and
      vertigo (30%). Clinical signs leading to admission to hospital were hemiparesis
      (60%), visual disorders with oculomotor disorders (20%) or visual field defects
      (20%) and cerebellar syndrome (35%). Eight patients (40%) reported repeated
      transient episodes of neurological deficits, prior to the diagnosis. The segment
      most commonly affected was V2-V3 (50%), followed by V3 (15%) and V2 (15%), V3-V4
      (10%) and proximal V4 (10%). All patients but one presented cerebral infarction.
      Eleven patients received first-line treatment with low molecular weight heparin
      (LMWH), and nine patients received aspirin. Three patients experienced a
      recurrence of symptoms, one under vitamin K antagonist (VKA) and 2 under aspirin.
      All three were switched to LMWH with success. Fifty-eight percent of the
      dissected arteries were occluded at long-term follow-up, although 73% of them
      were patent at the acute phase. CONCLUSION: Initial imaging must include
      posterior fossa vessels and the craniocervical region with V2-V3 segments.
      Conventional angiography may be indicated in the absence of a definitive
      diagnosis on noninvasive imaging. Healing of the dissected vertebral artery
      predominantly resulted in occlusion, which does not constitute a pejorative
      factor but indicates good quality healing.

PMID- 25845812
TI  - Preoperative embolization of intracranial meningiomas using n-butyl
      cyanoacrylate.
AB  - INTRODUCTION: Preoperative embolization for intracranial meningioma has been
      controversial for several decades. This study retrospectively reviewed our
      experience using n-butyl cyanoacrylate (n-BCA) to identify the factors for
      effective devascularization and procedure-related complications. METHODS: Fifty
      seven patients who underwent preoperative embolization with n-BCA were analyzed
      to collect the following data: age, sex, tumor size, location, pathology, and
      presence or absence of pial arterial supply. The predictive factors for total
      devascularization and complications were examined using univariate and
      multivariate analyses. RESULTS: Injected n-BCA penetrated into the tumor vessels
      in 51 cases (89%) but resulted in feeder occlusion in 6 (11%). Angiographic total
      devascularization was achieved in 29 cases (51%) and partial devascularization in
      28 (49%). Small size, superficial location, and absence of pial supply were
      independent factors for total devascularization. No major complication was
      encountered, but asymptomatic or transient adverse events occurred in nine
      patients and were significantly associated with elderly patients and large
      tumors. CONCLUSION: Preoperative embolization for intracranial meningiomas using
      n-BCA can attain effective devascularization without major complications. The
      effect of preoperative embolization on surgical resection or patient outcome is
      still unknown.

PMID- 25845813
TI  - Differentiation of solitary brain metastasis from glioblastoma multiforme: a
      predictive multiparametric approach using combined MR diffusion and perfusion.
AB  - INTRODUCTION: Solitary brain metastasis (MET) and glioblastoma multiforme (GBM)
      can appear similar on conventional MRI. The purpose of this study was to identify
      magnetic resonance (MR) perfusion and diffusion-weighted biomarkers that can
      differentiate MET from GBM. METHODS: In this retrospective study, patients were
      included if they met the following criteria: underwent resection of a solitary
      enhancing brain tumor and had preoperative 3.0 T MRI encompassing diffusion
      tensor imaging (DTI), dynamic contrast-enhanced (DCE), and dynamic susceptibility
      contrast (DSC) perfusion. Using co-registered images, voxel-based fractional
      anisotropy (FA), mean diffusivity (MD), K(trans), and relative cerebral blood
      volume (rCBV) values were obtained in the enhancing tumor and non-enhancing
      peritumoral T2 hyperintense region (NET2). Data were analyzed by logistic
      regression and analysis of variance. Receiver operating characteristic (ROC)
      analysis was performed to determine the optimal parameter/s and threshold for
      predicting of GBM vs. MET. RESULTS: Twenty-three patients (14 M, age 32-78 years
      old) met our inclusion criteria. Pathology revealed 13 GBMs and 10 METs. In the
      enhancing tumor, rCBV, K(trans), and FA were higher in GBM, whereas MD was lower,
      neither without statistical significance. In the NET2, rCBV was significantly
      higher (p = 0.05) in GBM, but MD was significantly lower (p < 0.01) in GBM. FA
      and K(trans) were higher in GBM, though not reaching significance. The best
      discriminative power was obtained in NET2 from a combination of rCBV, FA, and MD,
      resulting in an area under the curve (AUC) of 0.98. CONCLUSION: The combination
      of MR diffusion and perfusion matrices in NET2 can help differentiate GBM over
      solitary MET with diagnostic accuracy of 98%.

PMID- 25845814
TI  - Screening and preliminary validation of miRNAs with the regulation of hTERT in
      colorectal cancer.
AB  - The overexpression of human telomerase reverse transcriptase (hTERT) has been
      associated with the invasion and metastasis of colorectal cancer (CRC) and has
      received extensive attention, although the underlying mechanism involved remains
      unclear. The aim of the present study was to screen and preliminarily validate
      new tumor-suppressor microRNAs (miRNAs) that potentially inhibit hTERT expression
      and to assess its clinical significance. Screening for downregulated miRNAs in
      CRC tissues was performed by retrieving and analysing microRNA microarray data.
      miRNA candidates were then filtered by bioinformatics analysis. The expression of
      miRNAs candidates was verified by quantitative polymerase chain reaction in the
      CRC and corresponding normal tissues. Immunohistochemistry (IHC) was used for the
      detection of hTERT protein expression. Spearman's correlation coefficient between
      miRNA candidates and hTERT protein expression was calculated (r) to identify
      hTERT-targeting miRNAs. A survival analysis was performed to assess the
      prognostic significance of hTERT-targeting miRNAs in CRC. Eight miRNAs with the
      potential to interact with hTERT were predicted: miR-29c-3p, miR-124-3p, miR-133a
      3p, miR-133b, miR-138-5p, miR-150-5p, miR-378a-3p and miR-422a, respectively.
      Following detection of the miRNAs using RT-qPCR, miR-29c-3p was excluded. miR-138
      5p and miR-422a were observed to potentially interact with hTERT (r=-0.362,
      P=0.001; r=-0.306, P=0.005, respectively). The Kaplan-Meier survival curves
      demonstrating high- vs. low-expression group of miR-422a showed a highly
      significant difference in CRC patients (P=0.024), which suggests that the
      downregulation of miR-422a was associated with a poorer prognosis. The results
      indicated that miR-138-5p and miR-422a potentially inhibited hTERT expression in
      CRC, and suggest a potential application of miR-422a in prognosis prediction and
      CRC treatment. 

PMID- 25845816
TI  - The B32 cluster has the most stable bowl structure with a remarkable heptagonal
      hole.
AB  - The neutral B32 exhibits an aromatic bowl structure containing one heptagonal
      hole, while two anionic species, one having a bowl structure and the other a
      quasi-planar structure, are almost degenerate in energy. These findings not only
      give more insight into the structural features of boron clusters, but also
      present a key result explaining the presence of heptagonal holes in the fullerene
      B40. 

PMID- 25845815
TI  - What is wrong with non-respondents? Alcohol-, drug- and smoking-related mortality
      and morbidity in a 12-year follow-up study of respondents and non-respondents in
      the Danish Health and Morbidity Survey.
AB  - AIM: Response rates in health surveys have diminished over the last two decades,
      making it difficult to obtain reliable information on health and health-related
      risk factors in different population groups. This study compared cause-specific
      mortality and morbidity among survey respondents and different types of non
      respondents to estimate alcohol-, drug- and smoking-related mortality and
      morbidity among non-respondents. DESIGN: Prospective follow-up study of
      respondents and non-respondents in two cross-sectional health surveys. SETTING:
      Denmark. PARTICIPANTS: A total sample of 39 540 Danish citizens aged 16 years or
      older. MEASUREMENTS: Register-based information on cause-specific mortality and
      morbidity at the individual level was obtained for respondents (n = 28 072) and
      different types of non-respondents (refusals n = 8954; illness/disabled n = 731,
      uncontactable n = 1593). Cox proportional hazards models were used to examine
      differences in alcohol-, drug- and smoking-related mortality and morbidity,
      respectively, in a 12-year follow-up period. FINDINGS: Overall, non-response was
      associated with a significantly increased hazard ratio (HR) of 1.56 [95%
      confidence interval (CI) = 1.36-1.78] for alcohol-related morbidity, 1.88 (95% CI
      = 1.38-2.57) for alcohol-related mortality, 1.55 (95% CI = 1.27-1.88) for drug
      related morbidity, 3.04 (95% CI = 1.57-5.89) for drug-related mortality and 1.15
      (95% CI = 1.03-1.29) for smoking-related morbidity. The hazard ratio for smoking
      related mortality also tended to be higher among non-respondents compared with
      respondents, although no significant association was evident (HR = 1.14; 95% CI =
      0.95-1.36). Uncontactable and ill/disabled non-respondents generally had a higher
      hazard ratio of alcohol-, drug- and smoking-related mortality and morbidity
      compared with refusal non-respondents. CONCLUSION: Health survey non-respondents
      in Denmark have an increased hazard ratio of alcohol-, drug- and smoking-related
      mortality and morbidity compared with respondents, which may indicate more
      unfavourable health behaviours among non-respondents.

PMID- 25845817
TI  - Heidegger, ontological death, and the healing professions.
AB  - In Being and Time, Martin Heidegger introduces a unique interpretation of death
      as a kind of world-collapse or breakdown of meaning that strips away our ability
      to understand and make sense of who we are. This is an 'ontological death' in the
      sense that we cannot be anything because the intelligible world that we draw on
      to fashion our identities and sustain our sense of self has lost all
      significance. On this account, death is not only an event that we can
      physiologically live through; it can happen numerous times throughout the finite
      span of our lives. This paper draws on Arthur Frank's (At the will of the body:
      reflections on illness. Houghton, Boston, 1991) narrative of critical illness to
      concretize the experience of 'ontological death' and illuminate the unique
      challenges it poses for health care professionals. I turn to Heidegger's
      conception of 'resoluteness' (Entschlossenheit) to address these challenges,
      arguing for the need of health care professionals to help establish a discursive
      context whereby the critically ill can begin to meaningfully express and
      interpret their experience of self-loss in a way that acknowledges the structural
      vulnerability of their own identities and is flexible enough to let go of those
      that have lost their significance or viability. 

PMID- 25845818
TI  - Dual-System Use and Intermediate Health Outcomes among Veterans Enrolled in
      Medicare Advantage Plans.
AB  - OBJECTIVE: The concurrent use of multiple health care systems may duplicate or
      fragment care. We assessed the characteristics of veterans who were dually
      enrolled in both the Veterans Affairs (VA) health care system and a Medicare
      Advantage (MA) plan, and compared intermediate quality outcomes among those
      exclusively receiving care in the VA with those receiving care in both systems.
      DATA SOURCES/STUDY SETTING: VA and MA quality and administrative data from 2008
      to 2009. STUDY DESIGN: We used propensity score methods to test the association
      between dual use and five intermediate outcome quality measures. Outcomes
      included control of cholesterol, blood pressure, and glycosylated hemoglobin
      among persons with coronary heart disease (CHD), hypertension, and diabetes. DATA
      COLLECTION/EXTRACTION METHODS: VA and MA data were merged to identify VA-only
      users (n = 1,637) and dual-system users (n = 5,006). PRINCIPAL FINDINGS: We found
      no significant differences in intermediate outcomes between VA-only and dual-user
      populations. Differences ranged from a 3.2 percentage point (95 percent CI: -1.8
      to 8.2) greater rate of controlled cholesterol among VA-only users with CHD to a
      2.2 percentage point (95 percent CI: -2.4 to 6.6) greater rate of controlled
      blood pressure among dual users with diabetes. CONCLUSIONS: For the five measures
      studied, we did not find evidence that veterans with dual use of VA and MA care
      experienced improved or worsened outcomes as compared with veterans who
      exclusively used VA care.

PMID- 25845819
TI  - Guanine-based structural coloration as an indicator of oxidative stress in a
      cichlid fish.
AB  - Vertebrate pigmentation is known to be influenced by oxidative stress, but few
      studies have tested the hypothesis that structural coloration can be similarly
      affected. We tested whether fish iridophores, which produce structural color
      using guanine stacks, might be affected by the prooxidant-antioxidant balance of
      the animal. Specifically, we hypothesized that convict cichlids (Amatitlania
      nigrofasciata) metabolize guanine present in iridophores to uric acid, an
      antioxidant, in response to oxidative damage. We used Hunter's contrast gloss and
      high performance liquid chromatography to determine whether dietary guanine
      supplementation allows fish to maintain their structural coloration despite
      oxidative stress induced via ultraviolet-B (UV-B) radiation. We found that
      dietary guanine was associated with greater skin gloss, and that exposure to UV-B
      light reduced glossiness. UV-B exposure did not increase oxidative damage
      (acrolein) or total antioxidant capacity in the skin or liver. Our experiment did
      not detect effects of dietary guanine or UV-B light on uric acid, but uric acid
      was positively related to antioxidant capacity. Our results support the
      hypothesis that structural color in fish may be altered by environmental
      stressors such as exposure to UV light, and highlight the need for future studies
      to consider the role of iridophores in condition-dependent visual signaling.

PMID- 25845820
TI  - Adherence to a pedometer-based physical activity intervention following kidney
      transplant and impact on metabolic parameters.
AB  - The majority of kidney transplant recipients die from cardiovascular events.
      Physical activity may be a modifiable risk factor for cardiovascular disease
      following transplant. The goal of our study was to examine adherence to a
      physical activity intervention following kidney transplant and its impact on
      metabolic parameters. All patients who received a kidney transplant at our center
      between 12/2010 and 12/2011 received usual care (n = 162), while patients
      transplanted between 12/2011 and 1/2013 received a 90-day pedometer-based
      physical activity intervention (n = 145). Metabolic parameters were assessed at
      four and 12 months post-transplant. Baseline demographics and clinical management
      were similar between cohorts. Adherence to the prescription was 36.5%. Patients
      in the physical activity cohort had lower systolic and diastolic blood pressure
      four months post-transplant compared to the usual care cohort (122 +/- 18 vs. 126
      +/- 16 mmHg, p = 0.049 and 73 +/- 10 vs. 77 +/- 9, p = 0.004) and less impaired
      fasting glucose (20.7% vs. 30.9%, p = 0.04). Twelve-month outcomes were not
      different between cohorts. Over one-third of our cohort adhered to a pedometer
      based physical activity intervention following kidney transplant, and the
      intervention was associated with improved metabolic parameters. Further study of
      post-transplant exercise interventions and methods to optimize long-term
      adherence are needed.

PMID- 25845826
TI  - Prediction of in vivo clearance and associated variability of CYP2C19 substrates
      by genotypes in populations utilizing a pharmacogenetics-based mechanistic model.
AB  - It is important to examine the cytochrome P450 2C19 (CYP2C19) genetic
      contribution to drug disposition and responses of CYP2C19 substrates during drug
      development. Design of such clinical trials requires projection of genotype
      dependent in vivo clearance and associated variabilities of the investigational
      drug, which is not generally available during early stages of drug development,
      but is essential for CYP2C19 substrates with multiple clearance pathways. This
      study evaluated the utility of pharmacogenetics-based mechanistic modeling in
      predicting such parameters. Hepatic CYP2C19 activity and variability within
      genotypes were derived from in vitro S-mephenytoin metabolic activity in
      genotyped human liver microsomes (N = 128). These data were then used in
      mechanistic models to predict genotype-dependent disposition of CYP2C19
      substrates (i.e., S-mephenytoin, citalopram, pantoprazole, and voriconazole) by
      incorporating in vivo clearance or pharmacokinetics of wild-type subjects and
      parameters of other clearance pathways. Relative to the wild-type, the CYP2C19
      abundance (coefficient of variation percentage) in CYP2C19*17/*17, *1/*17, *1/*1,
      *17/null, *1/null, and null/null microsomes was estimated as 1.85 (117%), 1.79
      (155%), 1.00 (138%), 0.83 (80%), 0.38 (130%), and 0 (0%), respectively. The
      subsequent modeling and simulations predicted, within 2-fold of the observed, the
      means and variabilities of urinary S/R-mephenytoin ratio (36 of 37 genetic
      groups), the oral clearance of citalopram (9 of 9 genetic groups) and
      pantoprazole (6 of 6 genetic groups), and voriconazole oral clearance (4 of 4
      genetic groups). Thus, relative CYP2C19 genotype-dependent hepatic activity and
      variability were quantified in vitro and used in a mechanistic model to predict
      pharmacokinetic variability, thus allowing the design of pharmacogenetics and
      drug-drug interaction trials for CYP2C19 substrates. 

PMID- 25845827
TI  - A novel reaction mediated by human aldehyde oxidase: amide hydrolysis of GDC
      0834.
AB  - GDC-0834, a Bruton's tyrosine kinase inhibitor investigated as a potential
      treatment of rheumatoid arthritis, was previously reported to be extensively
      metabolized by amide hydrolysis such that no measurable levels of this compound
      were detected in human circulation after oral administration. In vitro studies in
      human liver cytosol determined that GDC-0834 (R)-N-(3-(6-(4-(1,4-dimethyl-3
      oxopiperazin-2-yl)phenylamino)-4-methyl-5-oxo- 4,5-dihydropyrazin-2-yl)-2
      methylphenyl)-4,5,6,7-tetrahydrobenzo[b] thiophene-2-carboxamide) was rapidly
      hydrolyzed with a CLint of 0.511 ml/min per milligram of protein. Aldehyde
      oxidase (AO) and carboxylesterase (CES) were putatively identified as the enzymes
      responsible after cytosolic fractionation and mass spectrometry-proteomics
      analysis of the enzymatically active fractions. Results were confirmed by a
      series of kinetic experiments with inhibitors of AO, CES, and xanthine oxidase
      (XO), which implicated AO and CES, but not XO, as mediating GDC-0834 amide
      hydrolysis. Further supporting the interaction between GDC-0834 and AO, GDC-0834
      was shown to be a potent reversible inhibitor of six known AO substrates with
      IC50 values ranging from 0.86 to 1.87 MUM. Additionally, in silico modeling
      studies suggest that GDC-0834 is capable of binding in the active site of AO with
      the amide bond of GDC-0834 near the molybdenum cofactor (MoCo), orientated in
      such a way to enable potential nucleophilic attack on the carbonyl of the amide
      bond by the hydroxyl of MoCo. Together, the in vitro and in silico results
      suggest the involvement of AO in the amide hydrolysis of GDC-0834. 

PMID- 25845828
TI  - Endothelial-to-mesenchymal transition induced by Wnt 3a in keloid pathogenesis.
AB  - Endothelial-to-mesenchymal transition is a phenotypic conversion characterized by
      down-regulation of vascular endothelial markers and the acquisition of a
      mesenchymal phenotype. We hypothesized that keloid fibroblasts are of endothelial
      origin and that endothelial-to-mesenchymal transition substantially contributes
      to collagen accumulation during the development and progression of keloids.
      Wingless protein (Wnt-3a) protein expression was examined using
      immunohistochemistry in keloid tissues. Human dermal microvascular endothelial
      cells (HDMECs) were treated with Wnt-3a. mRNA and protein expression of
      endothelial (vascular endothelial cadherin) and mesenchymal (vimentin, snail
      family transcription factor [slug], and alpha-smooth muscle actin) cell markers
      were measured using real-time RT-PCR and immunocytochemistry, respectively.
      Additionally, coexpression of CD31 (cluster of differentiation 31), and
      endothelial cell marker, and vimentin in the vascular endothelium of keloid
      tissues was examined using immunofluorescence. Wnt-3a overexpression was observed
      in human keloid tissues. Wnt-3a treatment significantly reduced vascular
      endothelial cadherin mRNA expression and induced vimentin and slug mRNA
      expression in HDMECs. HDMECs became spindle-shaped and exhibited reduced
      expression of CD31 and increased expression of vimentin, slug, and alpha-smooth
      muscle actin. Moreover, coexpression of CD31 and vimentin was observed in the
      dermal vascular endothelium of keloid tissues from two patients with clinically
      active keloids. In conclusion, transient conversion of HDMECs to a mesenchymal
      phenotype may contribute to dermal fibrosis of keloid and hypertrophic scars. 

PMID- 25845829
TI  - Urinary biomarkers for the detection of prostate cancer in patients with high
      grade prostatic intraepithelial neoplasia.
AB  - INTRODUCTION: High-grade prostatic intraepithelial neoplasia (HGPIN) is a
      recognized precursor stage of PCa. Men who present HGPIN in a first prostate
      biopsy face years of active surveillance including repeat biopsies. This study
      aimed to identify non-invasive prognostic biomarkers that differentiate early on
      between indolent HGPIN cases and those that will transform into actual PCa.
      METHODS: We measured the expression of 21 candidate mRNA biomarkers using
      quantitative PCR in urine sediment samples from a cohort of 90 patients with
      initial diagnosis of HGPIN and a posterior follow up of at least two years. Uni-
      and multivariate statistical analyses were applied to analyze the candidate
      biomarkers and multiplex models using combinations of these biomarkers. RESULTS:
      PSMA, PCA3, PSGR, GOLM, KLK3, CDH1, and SPINK1 behaved as predictors for PCa
      presence in repeat biopsies. Multiplex models outperformed (AUC = 0.81-0.86) the
      predictive power of single genes, including the FDA-approved PCA3 (AUC = 0.70).
      With a fixed sensitivity of 95%, the specificity of our multiplex models was of
      41-58%, compared to the 30% of PCA3. The PPV of our models (30-38%) was also
      higher than the PPV of PCA3 (27%), suggesting that benign cases could be more
      accurately identified. Applying statistical models, we estimated that 33% to 47%
      of repeat biopsies could be prevented with a multiplex PCR model, representing an
      easy applicable and significant advantage over the current gold standard in urine
      sediment. DISCUSSION: Using multiplex RTqPCR-based models in urine sediment it is
      possible to improve the current diagnostic method of choice (PCA3) to
      differentiate between benign HGPIN and PCa cases.

PMID- 25845830
TI  - Projections in donor organs available for liver transplantation in the United
      States: 2014-2025.
AB  - With the aging US population, demographic shifts, and obesity epidemic, there is
      potential for further exacerbation of the current liver donor shortage. We aimed
      to project the availability of liver grafts in the United States. We performed a
      secondary analysis of the Organ Procurement and Transplantation Network database
      of all adult donors from 2000 to 2012 and calculated the total number of donors
      available and transplanted donor livers stratified by age, race, and body mass
      index (BMI) group per year. We used National Health and Nutrition Examination
      Survey and Centers for Disease Control and Prevention historical data to stratify
      the general population by age, sex, race, and BMI. We then used US population age
      and race projections provided by the US Census Bureau and the Weldon Cooper
      Center for Public Service and made national and regional projections of available
      donors and donor liver utilization from 2014 to 2025. We performed sensitivity
      analyses and varied the rate of the rise in obesity, proportion of Hispanics,
      population growth, liver utilization rate, and donation after cardiac death (DCD)
      utilization. The projected adult population growth in the United States from 2014
      to 2025 will be 7.1%. However, we project that there will be a 6.1% increase in
      the number of used liver grafts. There is marked regional heterogeneity in liver
      donor growth. Projections were significantly affected by changes in BMI, DCD
      utilization, and liver utilization rates but not by changes in the Hispanic
      proportion of the US population or changes in the overall population growth.
      Overall population growth will outpace the growth of available donor organs and
      thus potentially exacerbate the existing liver graft shortage. The projected
      growth in organs is highly heterogeneous across different United Network for
      Organ Sharing regions. Focused strategies to increase the liver donor pool are
      warranted.

PMID- 25845831
TI  - Cortico-Cortical Connectivity Within Ferret Auditory Cortex.
AB  - Despite numerous studies of auditory cortical processing in the ferret (Mustela
      putorius), very little is known about the connections between the different
      regions of the auditory cortex that have been characterized cytoarchitectonically
      and physiologically. We examined the distribution of retrograde and anterograde
      labeling after injecting tracers into one or more regions of ferret auditory
      cortex. Injections of different tracers at frequency-matched locations in the
      core areas, the primary auditory cortex (A1) and anterior auditory field (AAF),
      of the same animal revealed the presence of reciprocal connections with
      overlapping projections to and from discrete regions within the posterior
      pseudosylvian and suprasylvian fields (PPF and PSF), suggesting that these
      connections are frequency specific. In contrast, projections from the primary
      areas to the anterior dorsal field (ADF) on the anterior ectosylvian gyrus were
      scattered and non-overlapping, consistent with the non-tonotopic organization of
      this field. The relative strength of the projections originating in each of the
      primary fields differed, with A1 predominantly targeting the posterior bank
      fields PPF and PSF, which in turn project to the ventral posterior field, whereas
      AAF projects more heavily to the ADF, which then projects to the anteroventral
      field and the pseudosylvian sulcal cortex. These findings suggest that parallel
      anterior and posterior processing networks may exist, although the connections
      between different areas often overlap and interactions were present at all
      levels.

PMID- 25845832
TI  - A week in the life of lung cancer survivors: Daily reports of stress, worry,
      mood, and symptoms.
AB  - This study examined the day-to-day lives of early stage lung cancer survivors who
      were discharged from treatment between 2 and 24 months prior to the study. Lung
      cancer survivors were called on eight consecutive nights and completed an
      interview about their daily experiences. Repeated measures, multilevel analysis
      of the phone interview data was conducted. Survivors reported few daily stressor
      exposures or somatic symptoms. Daily moods were generally positive, and survivors
      reported living quite independently. Lung cancer survivors did not report
      experiencing health-related worry on a daily basis. The findings from this study
      create a much more positive picture of lung cancer survivorship relative to prior
      studies.

PMID- 25845833
TI  - Granting wishes of seriously ill children: Effects on parents' well-being.
AB  - We investigated whether a positive intervention (i.e. granting a wish) in
      children with a chronic illness could promote positive psychological responses in
      their parents. Hospitalized children were randomly assigned to either the wish
      group or to a waiting-list control group. Mothers and fathers' responses (N = 86
      and 38, respectively) were studied. Parents from the wish group showed higher
      levels of positive emotions and beliefs in a benevolent world than the control
      group. Mothers from the wish group reported higher benefit finding, gratitude,
      and love than those in the control group. Given that the child's illness
      inevitably affects their parents, it is important to promote studies that include
      parents' well-being dimensions.

PMID- 25845834
TI  - Existential challenges experienced by lymphoma survivors: Results from the 2010
      LIVESTRONG Survey.
AB  - We sought to examine the existential challenges that cancer survivors may
      experience as they strive to make meaning, regain their self-identity, cope with
      fear of recurrence, and experience feelings of grief and guilt. Lymphoma
      survivors (n = 429) completed the 2010 LIVE STRONG: survey and provided responses
      about meaning, cancer worry, security, identity, grief, guilt, and perceived
      functional impairment due to these concerns. Most survivors (73%-86%) endorsed
      existential concerns, with 30-39 percent reporting related perceived functional
      impairment. Concerns were associated with being female, younger, unmarried, and
      having undergone stem cell transplantation. Lymphoma survivors experience
      existential challenges that impact their life even years after diagnosis.

PMID- 25845835
TI  - Caregivers' interest in using smokeless tobacco products: Novel methods that may
      reduce children's exposure to secondhand smoke.
AB  - The study examined caregivers' interest in using potentially reduced exposure
      tobacco products for smoking cessation, reduction, and to help them not smoke in
      places such as around their child, as all three methods would potentially lead to
      reduced secondhand smoke exposure for their children. A sample of 136 caregivers
      completed carbon monoxide testing to assess smoking status and a brief survey.
      Few caregivers had ever used potentially reduced exposure tobacco products (<1%),
      but a majority were interested in trying them as means of smoking reduction
      (54%), to quit/stay quit from smoking (51%), and to help them not smoke around
      their child or in the home (55%). Caregivers less motivated to quit smoking and
      with no home smoking ban were more interested in using potentially reduced
      exposure tobacco products to help them quit/stay quit from smoking (p < .05).

PMID- 25845836
TI  - Development and validation of the Eating Maturity Questionnaire: Preliminary
      findings.
AB  - This article describes the development of the Eating Maturity Questionnaire, a
      self-reported measurement of eating maturity that initiates and gives direction
      to human eating behaviors. The Eating Maturity Questionnaire was designed to
      study individuals' biological and psychosocial motives for eating. The Eating
      Maturity Questionnaire is a 21-item tool with satisfactory psychometric values
      (Cronbach's alpha coefficients between 0.83 and 0.88) consisting of two
      subscales: Rational Eating and Psychosocial Maturity Eating Maturity
      Questionnaire results may be used to design programs that target eating behaviors
      and body mass modification.

PMID- 25845837
TI  - Assessment of coagulation utilizing thromboelastometry in dogs undergoing
      orthopedic surgery.
AB  - OBJECTIVE: To evaluate blood coagulation using thromboelastometry in dogs
      following orthopedic surgery. DESIGN: Longitudinal observational study. SETTING:
      University veterinary teaching hospital. ANIMALS: Thirty-four adult client-owned
      dogs. MEASUREMENTS AND MAIN RESULTS: Dogs undergoing elective or emergency
      orthopedic surgery had whole blood collected before (T0), at 24 hours (T1), and 1
      week (T2) after surgery. Whole blood from each dog was collected by jugular
      venipuncture using a 20-Ga needle and minimum venous stasis. The blood was placed
      into tubes containing 3.8% trisodium citrate (1 part citrate: 9 parts blood) and
      rested at 37 degrees C. Coagulation was evaluated by means of thromboelastometry
      using the in-TEM, ex-TEM, and fib-TEM assays. Statistically significant increases
      (P < 0.05) in maximum clot firmness (MCF) from T0 to T1 in the in-TEM and fib-TEM
      profiles (both P = 0.0001), from T0 to T2 in the in-TEM, ex-TEM, and fib-TEM
      profiles (P = 0.012, P = 0.037, and P = 0.0001, respectively), and from T1 to T2
      in the fib-TEM profile (P = 0.039) were noted. The alpha angle increased from T0
      to T2 in the in-TEM and ex-TEM profiles (P = 0.019 and P = 0.036, respectively).
      All results were, however, within the institutional reference ranges.
      CONCLUSIONS: In this study, unlike the hypercoagulability observed in human
      orthopedic patients, a hypercoagulable state as measured by thromboelastometry
      did not develop in dogs following orthopedic surgery.

PMID- 25845838
TI  - The Ruthenostannylene Complex [Cp*(IXy)H2 Ru-Sn-Trip]: Providing Access to
      Unusual Ru-Sn Bonded Stanna-imine, Stannene, and Ketenylstannyl Complexes.
AB  - Reactivity studies of the thermally stable ruthenostannylene complex
      [Cp*(IXy)(H)2 Ru-Sn-Trip] (1; IXy=1,3-bis(2,6-dimethylphenyl)imidazol-2-ylidene;
      Cp*=eta(5) -C5 Me5 ; Trip=2,4,6-iPr3 C6 H2 ) with a variety of organic substrates
      are described. Complex 1 reacts with benzoin and an alpha,beta-unsaturated ketone
      to undergo [1+4] cycloaddition reactions and afford [Cp*(IXy)(H)2 RuSn(kappa(2) 
      O,O-OCPhCPhO)Trip] (2) and [Cp*(IXy)(H)2 RuSn(kappa(2) -O,C-OCPhCHCHPh)Trip] (3),
      respectively. The reaction of 1 with ethyl diazoacetate resulted in a tin
      substituted ketene complex [Cp*(IXy)(H)2 RuSn(OC2 H5 )(CHCO)Trip] (4), which is
      most likely a decomposition product from the putative ruthenium-substituted
      stannene complex. The isolation of a ruthenium-substituted stannene [Cp*(IXy)(H)2
      RuSn(=Flu)Trip] (5) and stanna-imine [Cp*(IXy)(H)2 RuSn(kappa(2) -N,O-NSO2 C6 H4
      Me)Trip] (6) complexes was achieved by treatment of 1 with 9-diazofluorene and
      tosyl azide, respectively.

PMID- 25845839
TI  - Plasma miRNAs as early biomarkers for detecting hepatocellular carcinoma.
AB  - The early detection of hepatocellular carcinoma (HCC) presents a challenge
      because of the lack of specific biomarkers. Serum/plasma microRNAs (miRNAs) can
      discriminate HCC patients from controls. We aimed to identify and evaluate HCC
      associated plasma miRNAs originating from the liver as early biomarkers for
      detecting HCC. In this multicenter three-phase study, we first performed
      screening using both plasma (HCC before and after liver transplantation or liver
      hepatectomy) and tissue samples (HCC, para-carcinoma and cirrhotic tissues).
      Then, we evaluated the diagnostic potential of the miRNAs in two case-control
      studies (training and validation sets). Finally, we used two prospective cohorts
      to test the potential of the identified miRNAs for the early detection of HCC.
      During the screening phase, we identified ten miRNAs, eight of which (miR-20a-5p,
      miR-25-3p, miR-30a-5p, miR-92a-3p, miR-132-3p, miR-185-5p, miR-320a and miR-324
      3p) were significantly overexpressed in the HBV-positive HCC patients compared
      with the HBV-positive cancer-free controls in both the training and validation
      sets, with a sensitivity of 0.866 and specificity of 0.646. Furthermore, we
      assessed the potential for early HCC detection of these eight newly identified
      miRNAs and three previously reported miRNAs (miR-192-5p, miR-21-5p and miR-375)
      in two prospective cohorts. Our meta-analysis revealed that four miRNAs (miR-20a
      5p, miR-320a, miR-324-3p and miR-375) could be used as preclinical biomarkers
      (pmeta  < 0.05) for HCC. The expression profile of the eight-miRNA panel can be
      used to discriminate HCC patients from cancer-free controls, and the four-miRNA
      panel (alone or combined with AFP) could be a blood-based early detection
      biomarker for HCC screening. 

PMID- 25845840
TI  - Is Innate Immunity and Inflammasomes Involved in Pathogenesis of Amyotrophic
      Lateral Sclerosis (ALS)?
AB  - Amyotrophic Lateral Sclerosis (ALS) or Lou Gehrig's disease is an axonopathy with
      adultonset, progressive and irreversible degeneration of upper and lower motor
      neurons. Around 90% of ALS is considered as sporadic ALS (sALS) without apparent
      genetic cause while in the familial type of ALS (fALS) at least one affected
      blood relative needs to be identified. Both sALS and fALS show similar
      progression and pathological profile. Biochemical and immunological roles have
      been reported for both types of ALS. It has been suggested that mutation in SOD1
      gene would be responsible for the oxidative stress and neurotoxicity. Besides,
      oxidative stress, protein aggregation, altered cholinergic synapse, neuro
      inflammation and production of pro-inflammatory cytokines have also been
      reported. Thus, the focus of the present review was on biochemical and
      immunological biomarkers and pathogenic mechanism. Regulatory T cells, pro
      inflammatory cytokines and activation of pro-inflammatory signaling pathway are
      discussed. The activation of NRL inflammasomes in ALS and the involvement of IL
      18, IL-1beta and caspases-1 are also suggested. The presence and importance of
      HMGB-1 (DAMP) and activation of Tolllike receptors and/or RAGE also are
      envisaged. The patents US20140212508, WO2014145776, WO2014145118, US20140255371,
      US20140194427, US20140243400, WO2014128254, WO2014076702, WO2014071449,
      WO2014043696, WO2014001742, and WO2013082299 are summarized. This review intends
      to evaluate the biochemical and immunological responses and the involvement of
      inflammasomes in the pathogenesis of ALS. In the present review, we suggest
      hypothetical model for ALS pathogenesis and we discuss some patents that suggest
      new treatment and/or therapeutic targets. Due to a large number of patents
      covering therapy and control of neurodegenerative diseases, our focus was
      restricted only to discuss the latest registered patents in 2014.

PMID- 25845841
TI  - Myocardial function and effects of biologic therapy in patients with severe
      psoriasis: a prospective echocardiographic study.
AB  - BACKGROUND: Psoriasis is a chronic inflammatory disease and is associated with
      cardiovascular events. Little is known about subclinical myocardial dysfunction
      and potential changes in myocardial function during anti-inflammatory treatment
      in these patients. We prospectively studied left ventricular function in patients
      with severe psoriasis who initiated biologic therapy. METHODS: Between November 1
      2013 and May 31 2014 the study subjects underwent physical, laboratory and
      comprehensive echocardiographic examination at baseline and after 3 months of
      treatment. Pearson correlation coefficients and Student's t-test were applied to
      assess changes in diastolic function (defined as the E/e' ratio) and global
      longitudinal strain (GLS). RESULTS: Eighteen patients with severe psoriasis
      treated with biologic therapy with a mean follow-up of 85.6 +/- 18.2 days were
      included. The patients had a baseline psoriasis area and severity index (PASI) of
      12.0 +/- 4.1 and normal left ventricular ejection fraction [(LVEF) 56.3 +/-
      3.8%], diastolic dysfunction (E/e' 8.1 +/- 2.1) and GLS (-16.8 +/- 2.1%). At
      follow-up, an improvement (baseline vs. follow-up) of PASI (12.0 +/- 4.1 vs. 2.7
      +/- 3.1, P < 0.001), E/e' (8.1 +/- 2.1 vs. 6.7 +/- 1.9, P <= 0.001) and GLS (
      16.8 +/- 2.1 vs. -18.3 +/- 2.3%, P < 0.001) were recorded. No changes were
      demonstrated in LVEF (56.3 +/- 3.8 vs. 56.8 +/- 3.3%, P = 0.31), body mass index
      (30.9 +/- 5.7 vs. 31.0 +/- 5.8 kg/m(2) , P = 0.90), mean arterial blood pressure
      (103.1 +/- 8.5 vs. 103.7 +/- 10.8 mmHg, P = 0.74). Likewise, no changes were seen
      in total cholesterol, low density lipoprotein cholesterol, high density
      lipoprotein cholesterol, estimated glomerular filtration rate and glycosylated
      haemoglobin. CONCLUSION: In patients with severe psoriasis treatment with
      biologic therapy was associated with improved PASI and amelioration of myocardial
      dysfunction.

PMID- 25845842
TI  - Biosynthesis of the Common Polysaccharide Antigen of Pseudomonas aeruginosa PAO1:
      Characterization and Role of GDP-D-Rhamnose:GlcNAc/GalNAc-Diphosphate-Lipid
      alpha1,3-D-Rhamnosyltransferase WbpZ.
AB  - The opportunistic pathogen Pseudomonas aeruginosa produces two major cell surface
      lipopolysaccharides, characterized by distinct O antigens, called common
      polysaccharide antigen (CPA) and O-specific antigen (OSA). CPA contains a polymer
      of D-rhamnose (D-Rha) in alpha1-2 and alpha1-3 linkages. Three putative
      glycosyltransferase genes, wbpX, wbpY, and wbpZ, are part of the CPA biosynthesis
      cluster. To characterize the enzymatic function of the wbpZ gene product, we
      chemically synthesized the donor substrate GDP-D-Rha and enzymatically
      synthesized GDP-D-[(3)H]Rha. Using nuclear magnetic resonance (NMR) spectroscopy,
      we showed that WbpZ transferred one D-Rha residue from GDP-D-Rha in alpha1-3
      linkage to both GlcNAc- and GalNAc-diphosphate-lipid acceptor substrates. WbpZ is
      also capable of transferring D-mannose (D-Man) to these acceptors. Therefore,
      WbpZ has a relaxed specificity with respect to both acceptor and donor
      substrates. The diphosphate group of the acceptor, however, is required for
      activity. WbpZ does not require divalent metal ion for activity and exhibits an
      unusually high pH optimum of 9. WbpZ from PAO1 is therefore a GDP-D
      Rha:GlcNAc/GalNAc-diphosphate-lipid alpha1,3-D-rhamnosyltransferase that has
      significant activity of GDP-D-Man:GlcNAc/GalNAc-diphosphate-lipid alpha1,3-D
      mannosyltransferase. We used site-directed mutagenesis to replace the Asp
      residues of the two DXD motifs with Ala. Neither of the mutant constructs of wbpZ
      (D172A or D254A) could be used to rescue CPA biosynthesis in the DeltawbpZ
      knockout mutant in a complementation assay. This suggested that D172 and D254 are
      essential for WbpZ function. This work is the first detailed characterization
      study of a D-Rha-transferase and a critical step in the development of CPA
      synthesis inhibitors. IMPORTANCE: This is the first characterization of a D
      rhamnosyltransferase and shows that it is essential in Pseudomonas aeruginosa for
      the synthesis of the common polysaccharide antigen.

PMID- 25845843
TI  - Secretion of Flagellar Proteins by the Pseudomonas aeruginosa Type III Secretion
      Injectisome System.
AB  - The opportunistic pathogen Pseudomonas aeruginosa utilizes an injectisome-type
      III secretion system (injectisome-T3SS) to elicit cytotoxicity toward epithelial
      cells and macrophages. Macrophage killing results from the cytotoxic properties
      of the translocated effector proteins (ExoS, ExoT, ExoU, and ExoY) and
      inflammasome-mediated induction of pyroptosis. Inflammasome activation can occur
      following Nlrc4-mediated recognition of cytosolic translocated flagellin (FliC).
      In the present study, we demonstrate that FliC is a secretion substrate of both
      the injectisome- and flagellum-associated T3SSs. Molecular analyses indicate that
      the first 20 amino-terminal residues of FliC are sufficient for secretion by the
      injectisome-T3SS and that the first 100 residues are sufficient for translocation
      of FliC into host cells. Although maximal inflammasome activation requires FliC,
      activation can also occur in the absence of FliC. This prompted us to examine
      whether other flagellar components might also be translocated into cells to
      elicit inflammasome activation. Indeed, we find that the flagellar cap (FliD),
      hook-associated (FlgK and FlgL), hook (FlgE), and rod (FlgE) proteins are
      secretion substrates of the injectisome-T3SS. None of these proteins, however,
      result in increased inflammasome activation when they are overexpressed in a fliC
      mutant and appear to be translocated into host cells. While a role in
      inflammasome activation has been excluded, these data raise the possibility that
      flagellar components, which are highly conserved between different bacterial
      species, trigger other specific host responses from the extracellular milieu or
      contribute to the pathogenesis of P. aeruginosa. IMPORTANCE: The inflammasome is
      a host defense mechanism that recognizes invading bacteria and triggers an
      inflammatory immune response. The opportunistic pathogen P. aeruginosa produces
      both inflammasome agonists and antagonists. In this study, we demonstrate that
      overexpression of an agonist suppresses the activity of an antagonist, thereby
      resulting in inflammasome activation. Since the relative expression levels of
      agonists and antagonists likely vary between strains, these differences could be
      important predictors of whether a particular P. aeruginosa strain elicits
      inflammasome activation.

PMID- 25845844
TI  - CysB Negatively Affects the Transcription of pqsR and Pseudomonas Quinolone
      Signal Production in Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa is a Gram-negative bacterium that is ubiquitous in the
      environment, and it is an opportunistic pathogen that can infect a variety of
      hosts, including humans. During the process of infection, P. aeruginosa
      coordinates the expression of numerous virulence factors through the production
      of multiple cell-to-cell signaling molecules. The production of these signaling
      molecules is linked through a regulatory network, with the signal N-(3
      oxododecanoyl) homoserine lactone and its receptor LasR controlling the induction
      of a second acyl-homoserine lactone signal and the Pseudomonas quinolone signal
      (PQS). LasR-mediated control of PQS occurs partly by activating the transcription
      of pqsR, a gene that encodes the PQS receptor and is necessary for PQS
      production. We show that LasR interacts with a single binding site in the pqsR
      promoter region and that it does not influence the transcription of the
      divergently transcribed gene, nadA. Using DNA affinity chromatography, we
      identified additional proteins that interact with the pqsR-nadA intergenic
      region. These include the H-NS family members MvaT and MvaU, and CysB, a
      transcriptional regulator that controls sulfur uptake and cysteine biosynthesis.
      We show that CysB interacts with the pqsR promoter and that CysB represses pqsR
      transcription and PQS production. Additionally, we provide evidence that CysB can
      interfere with the activation of pqsR transcription by LasR. However, as seen
      with other CysB-regulated genes, pqsR expression was not differentially regulated
      in response to cysteine levels. These findings demonstrate a novel role for CysB
      in influencing cell-to-cell signal production by P. aeruginosa. IMPORTANCE: The
      production of PQS and other 4-hydroxy-2-alkylquinolone (HAQs) compounds is a key
      component of the P. aeruginosa cell-to-cell signaling network, impacts multiple
      physiological functions, and is required for virulence. PqsR directly regulates
      the genes necessary for HAQ production, but little is known about the regulation
      of pqsR. We identified CysB as a novel regulator of pqsR and PQS production, but,
      unlike other CysB-controlled genes, it does not appear to regulate pqsR in
      response to cysteine. This implies that CysB functions as both a cysteine
      responsive and cysteine-unresponsive regulator in P. aeruginosa.

PMID- 25845845
TI  - Resources for Genetic and Genomic Analysis of Emerging Pathogen Acinetobacter
      baumannii.
AB  - Acinetobacter baumannii is a Gram-negative bacterial pathogen notorious for
      causing serious nosocomial infections that resist antibiotic therapy. Research to
      identify factors responsible for the pathogen's success has been limited by the
      resources available for genome-scale experimental studies. This report describes
      the development of several such resources for A. baumannii strain AB5075, a
      recently characterized wound isolate that is multidrug resistant and displays
      robust virulence in animal models. We report the completion and annotation of the
      genome sequence, the construction of a comprehensive ordered transposon mutant
      library, the extension of high-coverage transposon mutant pool sequencing (Tn
      seq) to the strain, and the identification of the genes essential for growth on
      nutrient-rich agar. These resources should facilitate large-scale genetic
      analysis of virulence, resistance, and other clinically relevant traits that make
      A. baumannii a formidable public health threat. IMPORTANCE: Acinetobacter
      baumannii is one of six bacterial pathogens primarily responsible for antibiotic
      resistant infections that have become the scourge of health care facilities
      worldwide. Eliminating such infections requires a deeper understanding of the
      factors that enable the pathogen to persist in hospital environments, establish
      infections, and resist antibiotics. We present a set of resources that should
      accelerate genome-scale genetic characterization of these traits for a reference
      isolate of A. baumannii that is highly virulent and representative of current
      outbreak strains.

PMID- 25845846
TI  - Methenyl-Dephosphotetrahydromethanopterin Is a Regulatory Signal for Acclimation
      to Changes in Substrate Availability in Methylobacterium extorquens AM1.
AB  - During an environmental perturbation, the survival of a cell and its response to
      the perturbation depend on both the robustness and functionality of the metabolic
      network. The regulatory mechanisms that allow the facultative methylotrophic
      bacterium Methylobacterium extorquens AM1 to effect the metabolic transition from
      succinate to methanol growth are not well understood. Methenyl
      dephosphotetrahydromethanopterin (methenyl-dH4MPT), an early intermediate during
      methanol metabolism, transiently accumulated 7- to 11-fold after addition of
      methanol to a succinate-limited culture. This accumulation partially inhibited
      the activity of the methylene-H4MPT dehydrogenase, MtdA, restricting carbon flux
      to the assimilation cycles. A strain overexpressing the gene (mch) encoding the
      enzyme that consumes methenyl-dH4MPT did not accumulate methenyl-dH4MPT and had a
      growth rate that was 2.7-fold lower than that of the wild type. This growth
      defect demonstrates the physiological relevance of this enzymatic regulatory
      mechanism during the acclimation period. Changes in metabolites and enzymatic
      activities were analyzed in the strain overexpressing mch. Under these
      conditions, the activity of the enzyme coupling formaldehyde with dH4MPT (Fae)
      remained constant, with concomitant formaldehyde accumulation. Release of
      methenyl-dH4MPT regulation did not affect the induction of the serine cycle
      enzyme activities immediately after methanol addition, but after 1 h, the
      activity of these enzymes decreased, likely due to the toxicity of formaldehyde
      accumulation. Our results support the hypothesis that in a changing environment,
      the transient accumulation of methenyl-dH4MPT and inhibition of MtdA activity are
      strategies that permit flexibility and acclimation of the metabolic network while
      preventing the accumulation of the toxic compound formaldehyde. IMPORTANCE: The
      identification and characterization of regulatory mechanisms for methylotrophy
      are in the early stages. We report a nontranscriptional regulatory mechanism that
      was found to operate as an immediate response for acclimation during changes in
      substrate availability. Methenyl-dH4MPT, an early intermediate during methanol
      oxidation, reversibly inhibits the methylene-H4MPT dehydrogenase, MtdA, when
      Methylobacterium extorquens is challenged to switch from succinate to methanol
      growth. Bypassing this regulatory mechanism causes formaldehyde to accumulate.
      Fae, the enzyme catalyzing the conversion of formaldehyde to methylene-dH4MPT,
      was also identified as another potential regulatory target using this strategy.
      The results herein further our understanding of the complex regulatory network in
      methylotrophy and will allow us to improve metabolic engineering strategies of
      methylotrophs for the production of value-added products.

PMID- 25845849
TI  - Male-male affiliation and cooperation characterize the social behavior of the
      large-bodied pitheciids, Chiropotes and Cacajao: A review.
AB  - Cooperation and affiliation between males may be key to the evolution of large
      multimale-multifemale primate groups in some species. Cacajao and Chiropotes form
      multimale-multifemale groups larger than those of most other platyrrhines
      (Cacajao: over 150 and Chiropotes: up to 80 individuals), and groups exhibit a
      high degree of fission-fusion dynamics. In both genera, males engage in
      affiliative, sex-specific behaviors and form all-male parties. Males in both
      genera also have conspicuous genitalia but can demonstrate sexual crypsis, or
      mimicry, wherein testes are retracted, resembling labia. Observed egalitarian
      interactions among males suggest that there is scramble competition for access to
      females, and aggression between males is uncommon relative to other social
      primates. As of yet, there are no genetic data to clarify dispersal patterns, and
      while relatedness among males would in part explain their affiliative
      relationships, there is some limited evidence for dispersal by males in Cacajao.
      In this review of recent studies of male-male social interactions in Chiropotes
      and Cacajao, we posit that the ability to maintain large groups in these genera
      may be related to the affiliative and perhaps coalitionary relationships between
      males, who may or may not be related. Affiliative male-male relationships may
      allow for monopolization of groups of females and facilitate group cohesion by
      reducing intragroup aggression; however data on male-male interactions with
      identified individuals will be required to determine patterns of affiliation,
      while genetic studies may be the most practical way of determining dispersal
      patterns for these genera.

PMID- 25845847
TI  - Distinct Paths for Basic Amino Acid Export in Escherichia coli: YbjE (LysO)
      Mediates Export of L-Lysine.
AB  - In Escherichia coli, argO encodes an exporter for L-arginine (Arg) and its toxic
      analogue canavanine (CAN), and its transcriptional activation and repression, by
      Arg and L-lysine (Lys), respectively, are mediated by the regulator ArgP.
      Accordingly argO and argP mutants are CAN supersensitive (CAN(ss)). We report the
      identification of ybjE as a gene encoding a predicted inner membrane protein that
      mediates export of Lys, and our results confirm the previous identification with
      a different approach of YbjE as a Lys exporter, reported by Ueda and coworkers
      (T. Ueda, Y. Nakai, Y. Gunji, R. Takikawa, and Y. Joe, U.S. patents 7,629,142 B2
      [December 2009] and 8,383,363 B1 [February 2013] and European patent 1,664,318 B1
      [September 2009]). ybjE was isolated as a multicopy suppressor of the CAN(ss)
      phenotype of a strain lacking ArgO. The absence of YbjE did not confer a CAN(ss)
      phenotype but instead conferred hypersensitivity to the lysine antimetabolite
      thialysine and led to growth inhibition by the dipeptide lysylalanine, which is
      associated with elevated cellular Lys content. YbjE overproduction resulted in
      Lys excretion and syntrophic cross-feeding of a Lys auxotroph. Constitutive
      overexpression of argO promoted Lys cross-feeding that is indicative of a latent
      Lys export potential of ArgO. Arg modestly repressed ybjE transcription in an
      ArgR-dependent manner, and ArgR displayed Arg-sensitive binding to the ybjE
      promoter region in vitro. Our studies suggest that the reciprocal repression of
      argO and ybjE, respectively, by Lys and Arg confers the specificity for basic
      amino acid export by distinct paths and that such cross-repression contributes to
      maintenance of cytoplasmic Arg/Lys balance. We propose that YbjE be redesignated
      LysO. IMPORTANCE: This work ascribes a lysine export function to the product of
      the ybjE gene of Escherichia coli, leading to a physiological scenario wherein
      two proteins, ArgO and YbjE, perform the task of separately exporting arginine
      and lysine, respectively, which is distinct from that seen for Corynebacterium
      glutamicum, where the ortholog of ArgO, LysE, mediates export of both arginine
      and lysine. Repression of argO transcription by lysine is thought to effect this
      separation. Accordingly, ArgO mediates lysine export when repression of its
      transcription by lysine is bypassed. Repression of ybjE transcription by arginine
      via the ArgR repressor, together with the lysine repression of argO effected by
      ArgP, is indicative of a mechanism of maintenance of arginine/lysine balance in
      E. coli.

PMID- 25845848
TI  - Asthma and allergy in children with and without prior measles, mumps, and rubella
      vaccination.
AB  - BACKGROUND: The existing literature on the association between measles
      vaccination and subsequent risk of allergic disease is inconclusive. The aim of
      this study was, therefore, to determine whether measles, mumps, and rubella (MMR)
      vaccination administered in early childhood was associated with asthma and
      allergic diseases at ages 5, 7 and 13 yrs in a birth cohort. METHODS: In the
      Faroe Islands, 640 children were followed from birth. Follow-up examinations at
      ages 5, 7 and 13 yrs included a physical examination and a maternal questionnaire
      about the child's health. At age 7, total and grass-specific IgE was quantified
      in the child's serum, and at age 13, the children underwent skin prick tests
      (SPT). The child's vaccination card was reviewed at examinations. RESULTS: At age
      5, 533 of 555 children had been vaccinated for MMR. After confounder adjustment,
      we found early life MMR vaccination to be associated with a two-third reduction
      in the odds of asthma (OR: 0.33, 95% CI: 0.12; 0.90) and hypersensitivity/allergy
      (OR: 0.32, 95% CI: 0.11; 0.88) at age 5, and the substantially decreased odds of
      asthma were replicated at age 13 (OR: 0.22, 95% CI: 0.08; 0.56). At age 7, serum
      total IgE was reduced by 62.8% (CI 95%: -84.3%; -11.9%) in the vaccinated
      children. MMR vaccination was not significantly associated with allergic
      rhinoconjuctivitis symptoms, eczema, or SPT reactions at age 13. CONCLUSIONS: MMR
      vaccination early in life may have a protective effect against allergy at least
      up to age 7 and against asthma through age 13 yrs.

PMID- 25845850
TI  - High-mobility-group A2 overexpression provokes a poor prognosis of gastric cancer
      through the epithelial-mesenchymal transition.
AB  - Tumor metastases are the ultimate target in cancer therapy. In epithelial
      malignancies, the expression of high-mobility-group A2 (HMGA2) is associated with
      disease progression and the epithelial-mesenchymal transition (EMT), which is
      involved in the metastatic process. The present study assessed the clinical and
      molecular effects of HMGA2 with the malignant tissues of 170 patients with
      gastric cancer and gastric cancer cells expressing HMGA2. HMGA2 expression was
      determined using immunohistochemistry and analyzed with respect to the
      clinicopathological data of patients with this tumor. In the gastric cancer cell
      line MKN28, in which HMGA2 was knocked down by two different short-hairpin RNAs,
      Transwell migration and invasion assays were conducted and western blotting was
      used to detect the altered expression of EMT markers. In patients with gastric
      cancer, HMGA2 overexpression correlated with tumor progression and was indicative
      of a significantly worse overall survival. Migration and invasion assays using
      HMGA2-knocked down MKN28 cells showed a reduction in cell migration and invasion.
      The upregulation of E-cadherin, an epithelial marker, and the downregulation of N
      cadherin, a mesenchymal marker were observed in HMGA2-knocked down cells. In
      addition, expression of the transcriptional factors Snail and Zeb1 and of the EMT
      pathway molecule beta-catenin were decreased. HMGA2 overexpression, through its
      relationship to EMT, thus seems to aggravate invasion and metastasis in gastric
      cancer. It may therefore serve as a predictive marker in determining the clinical
      outcome of patients with gastric cancer and offer a promising therapeutic target.

PMID- 25845852
TI  - Mode of delivery and childhood hospitalizations for asthma and other wheezing
      disorders.
AB  - BACKGROUND: Observationally, delivery by Caesarean section is associated with
      higher risk of childhood asthma and wheeze in developed Western settings, but
      associations are less consistent in other settings. OBJECTIVE: To examine the
      association of mode of delivery with hospitalizations for asthma and other
      wheezing disorders in a developed non-Western setting with high rates of
      Caesarean section. METHODS: Using Cox regression, we examined the adjusted
      association of mode of delivery with public hospital admissions for asthma,
      bronchitis, and bronchiolitis (International Classification of Diseases, Ninth
      Version Clinical Modification 466, 490 and 493) from 9 days to 12 years of age in
      a population-representative prospective birth cohort of 8327 Chinese children in
      Hong Kong. Confounders included sex, birth and parental characteristics, and
      socio-economic position (SEP). RESULTS: Delivery by Caesarean section accounted
      for 27% of all births and was not clearly associated with hospitalizations for
      asthma and other wheezing disorders to 12 years [hazard ratio (HR) 1.11, 95%
      confidence interval (CI) 0.91 to 1.36] compared to vaginal delivery. Similarly,
      there were no clear associations to 2 years (HR 1.07, 95% CI 0.83 to 1.38) or 6
      years (HR 1.12, 95% CI 0.91 to 1.37), although we cannot rule out residual
      confounding by SEP. CONCLUSIONS AND CLINICAL RELEVANCE: We cannot rule out an
      association, but our findings suggest that the observed associations of delivery
      by Caesarean section with childhood wheezing disorders may vary with setting and
      may not be biologically mediated. Further studies with different designs are
      needed to clarify the role of the microbiome and mode of delivery in the
      aetiology of asthma and other childhood wheezing disorders.

PMID- 25845851
TI  - Quantification of cell size using temporal diffusion spectroscopy.
AB  - PURPOSE: A new approach has been developed to quantify cell sizes and
      intracellular volume fractions using temporal diffusion spectroscopy with
      diffusion-weighted acquisitions. METHODS: Temporal diffusion spectra may be used
      to characterize tissue microstructure by measuring the effects of restrictions
      over a range of diffusion times. Oscillating gradients have been used previously
      to probe variations on cellular and subcellular scales, but their ability to
      accurately measure cell sizes larger than 10 MUm is limited. By combining
      measurements made using oscillating gradient spin echo (OGSE) and a conventional
      pulsed gradient spin echo (PGSE) acquisition with a single, relatively long
      diffusion time, we can accurately quantify cell sizes and intracellular volume
      fractions. RESULTS: Based on a two compartment model (incorporating intra- and
      extracellular spaces), accurate estimates of cell sizes and intracellular volume
      fractions were obtained in vitro for (i) different cell types with sizes ranging
      from 10 to 20 MUm, (ii) different cell densities, and (iii) before and after
      anticancer treatment. CONCLUSION: Hybrid OGSE-PGSE acquisitions sample a larger
      region of temporal diffusion spectra and can accurately quantify cell sizes over
      a wide range. Moreover, the maximum gradient strength used was lower than 15
      G/cm, suggesting that this approach is translatable to practical MR imaging.

PMID- 25845853
TI  - Endoscopic surgical treatment of maxillary odontogenic cysts.

PMID- 25845854
TI  - An electrodiagnostic technique for assessing palmar proper digital nerves of the
      hand: Normative data and clinical application.
AB  - INTRODUCTION: There is no standard electrodiagnostic technique for palmar proper
      digital nerves (PaPDNs). In this study we investigated sensory nerve action
      potentials (SNAPs) to PaPDN stimulation in normal subjects and patients. METHODS:
      SNAPs of PaPDNs were recorded in response to selective antidromic stimulation at
      the web space and mixed nerve stimulation at the wrist in 14 controls. The
      selectivity of PaPDN stimulation and the effect of recording electrode position
      on SNAP amplitude were studied. The technique was tested in 2 patients with PaPDN
      lesions. RESULTS: The technique yielded selective PaPDN stimulation at the web
      space. SNAP amplitude to PaPDN stimulation was influenced by age and was larger
      than SNAP amplitude to wrist stimulation. The recording electrode positions
      influenced SNAP amplitude. In patients, we documented PaPDN lesions, which were
      confirmed at surgery, whereas conventional wrist mixed nerve stimulation yielded
      negative findings. CONCLUSIONS: Selective PaPDN stimulation at the web space is
      feasible and may be helpful for electrodiagnosis of PaPDN lesions.

PMID- 25845855
TI  - The role of fat and alcohol in acute pancreatitis: A dangerous liaison.
AB  - Excessive alcohol consumption is a major trigger for severe acute pancreatitis
      which may lead to multi-organ dysfunction and premature death of the individual.
      Hyperlipidaemia is a risk factor for both acute and chronic pancreatitis and the
      role of fatty acids in mediating damage has received increasing attention in
      recent years. In the pancreas ethanol is metabolised by both oxidative and non
      oxidative pathways. The latter, predominant route generates fatty acid ethyl
      esters (FAEEs) from fatty acid substrates via the action of diverse enzymes
      called FAEE synthases, including carboxylester lipase an enzyme synthesized and
      secreted by the acinar cells. Inhibition of the oxidative pathway promotes
      formation of FAEEs which induce sustained elevations of cytosolic calcium leading
      to inhibition of mitochondrial function, loss of ATP and necrosis of isolated
      pancreatic acinar cells. Furthermore, FAEEs undergo hydrolysis in the
      mitochondria releasing free fatty acids that exert toxic effects. Our recent work
      has shown that pharmacological inhibition of carboxylester lipase ameliorated
      detrimental effects of non-oxidative ethanol metabolism in isolated pancreatic
      acinar cells in vitro and in a new in vivo experimental model of alcoholic acute
      pancreatitis, revealing a specific enzyme target for ethanol-induced injury.
      Strategies that prevent FAEE synthesis, protect mitochondria, reduce calcium
      overload or sustain calcium homeostasis by ATP provision may provide promising
      therapeutic avenues for the treatment of alcoholic acute pancreatitis. 

PMID- 25845856
TI  - Pancreatic cancer: The microenvironment needs attention too!
AB  - The abundant stromal/desmoplastic reaction, a characteristic feature of a
      majority of pancreatic adenocarcinomas (PDAC), has only recently been receiving
      some attention regarding its possible role in the pathobiology of pancreatic
      cancer. It is now well established that the cells predominantly responsible for
      producing the collagenous stroma are pancreatic stellate cells (PSCs). In
      addition to extracellular matrix proteins, the stroma also exhibits cellular
      elements including, immune cells, endothelial cells and neural cells. Evidence is
      accumulating to indicate the presence of significant interactions between PSCs
      and cancer cells as well as between PSCs and other cell types in the stroma. The
      majority of research reports to date, using in vitro and in vivo approaches,
      suggest that these interactions facilitate local growth as well as distant
      metastasis of pancreatic cancer, although a recent study using animals depleted
      of myofibroblasts has raised some questions regarding the central role of
      myofibroblasts in cancer progression. Nonetheless, novel therapeutic strategies
      have been assessed, mainly in the pre-clinical setting, in a bid to interrupt
      stromal-tumour interactions and inhibit disease progression. The next important
      challenge is for the translation of such pre-clinical strategies to the clinical
      situation so as to improve the outcome of patients with pancreatic cancer. 

PMID- 25845857
TI  - Feasibility of Lung Volume Recruitment in Early Neuromuscular Weakness: A
      Comparison Between Amyotrophic Lateral Sclerosis, Myotonic Dystrophy, and
      Postpolio Syndrome.
AB  - BACKGROUND: Lung volume recruitment (LVR) is a cough assistance technique used in
      persons with neuromuscular disorders (NMDs), most typically in those requiring
      noninvasive ventilation (NIV). Whether it may be useful in persons with NMDs who
      have milder respiratory impairment is unknown. OBJECTIVE: To assess the
      feasibility, impact on quality of life (QOL), and preliminary physiological
      effects of daily LVR in different categories of persons with NMDs who have an
      early stage of respiratory impairment. DESIGN: Feasibility study. SETTING:
      Academic tertiary care center. PARTICIPANTS: Outpatients diagnosed with
      amyotrophic lateral sclerosis (n = 8), postpolio syndrome (n = 10), and myotonic
      dystrophy (n = 6) who had restrictive respiratory defects but were not yet using
      NIV. METHODS: Participants were asked to perform LVR up to 4 times daily and log
      their LVR use in a diary. Physiological measurements and questionnaires were
      completed at baseline and after 3 months. MAIN OUTCOME MEASUREMENTS: Compliance
      with LVR use was assessed, along with QOL and willingness to continue the
      treatment. Physiological measurements included forced vital capacity (FVC), lung
      insufflation capacity (LIC), and the LIC minus FVC difference. RESULTS: Of the 24
      recruited subjects, 7 with amyotrophic lateral sclerosis, 7 with postpolio
      syndrome, and 5 with myotonic dystrophy completed the study (n = 19). At
      baseline, mean values for FVC and spontaneous peak cough flow were 59.9%
      predicted and 373.1 L/min, respectively. For subjects completing the study, 74%
      were willing to continue long-term LVR use, and QOL scores were not adversely
      affected by LVR in any NMD subgroup. The LIC-FVC difference increased from
      baseline to follow-up by a mean of 0.243 L (P = .006) in all subjects (n = 19),
      suggesting a possible improvement in respiratory system mechanics. CONCLUSIONS:
      In patients with NMDs who have early restrictive respiratory defects but do not
      yet require NIV, regular use of LVR is feasible with no negative impact on QOL
      over a 3-month period and may have physiological benefits. Further work is needed
      to determine whether early institution of LVR can improve respiratory system
      mechanics and help delay ventilatory failure in persons with NMDs.

PMID- 25845858
TI  - Conflicts of Interest in Medical Technology Markets: Evidence from Orthopedic
      Surgery.
AB  - Financial relationships between physicians and industry are vital to biomedical
      innovation yet create the potential for conflicts of interest in medical
      practice. I consider an inducement model of the role of financial relationships
      in health care markets, where consulting payments induce physicians to use more
      devices of the firms that sponsor them. To test the model, I exploit a policy
      shock, whereby government monitoring of payments to joint replacement surgeons
      resulted in declines of over 60% in both total payments and in the number of
      physicians receiving payments from 2007 to 2008. Using hospital discharge data
      from three states, I find that the loss of payments leads physicians to switch 7
      percentage points of their device utilization from their sponsoring firms'
      devices to other firms' devices, an effect which is concentrated among surgeons
      with low switching costs. These results offer support for the inducement model. I
      also find evidence of an increase in medical productivity following the policy
      intervention, which suggests conditions under which regulation of financial
      relationships would be socially beneficial. Copyright (c) 2015 John Wiley & Sons,
      Ltd.

PMID- 25845859
TI  - Characterization of multiple constituents in Kai-Xin-San prescription and rat
      plasma after oral administration by liquid chromatography with quadrupole time-of
      flight tandem mass spectrometry.
AB  - A sensitive and reliable ultra high performance liquid chromatography coupled
      with quadrupole-time-of-flight mass spectrometry method was established to
      separate and identify the chemical constituents of Kai-Xin-San prescription, a
      classic traditional Chinese medicine formula that plays an important role in the
      treatment of Alzheimer's disease. The detection was performed on an Agilent 6520
      Accurate-Mass quadrupole time-of-flight mass spectrometer equipped with an
      electrospray ionization source in negative modes. With the optimized conditions,
      a total of 54 compounds were identified or tentatively characterized. Out of the
      54 compounds, six compounds were identified by comparing the retention time and
      mass spectrometry data with reference standards, the rest were characterized by
      analyzing mass spectrometry data and retrieving the literature data. Results
      indicated ginsenosides, polygala saponins, terpenoids, and oligosaccharide esters
      were the major effective constituents in Kai-Xin-San prescription. There were 26
      prototype ingredients that were assigned for identification in rat plasma. It is
      also concluded that the developed ultra high performance liquid chromatography
      coupled with quadrupole-time-of-flight mass spectrometry method with high
      sensitivity and resolution is suitable for identifying and characterizing the
      chemical constituents of Kai-Xin-San prescription, and the analysis provides a
      helpful chemical basis for further research on Kai-Xin-San prescription and the
      clinical diagnostics of Alzheimer's disease. 

PMID- 25845860
TI  - The sheep as a model of preclinical safety and pharmacokinetic evaluations of
      candidate microbicides.
AB  - When developing novel microbicide products for the prevention of HIV infection,
      the preclinical safety program must evaluate not only the active pharmaceutical
      ingredient but also the product itself. To that end, we applied several
      relatively standard toxicology study methodologies to female sheep, incorporating
      an assessment of the pharmacokinetics, safety, tolerability, and local toxicity
      of a dapivirine-containing human vaginal ring formulation (Dapivirine Vaginal
      Ring-004). We performed a 3-month general toxicology study, a preliminary
      pharmacokinetic study using drug-loaded vaginal gel, and a detailed assessment of
      the kinetics of dapivirine delivery to plasma, vaginal, and rectal fluid and
      rectal, vaginal, and cervical tissue over 28 days of exposure and 3 and 7 days
      after removal of the ring. The findings of the general toxicology study supported
      the existing data from both preclinical and clinical studies in that there were
      no signs of toxicity related to dapivirine. In addition, the presence of the
      physical dapivirine ring did not alter local or systemic toxicity or the
      pharmacokinetics of dapivirine. Pharmacokinetic studies indicated that the
      dapivirine ring produced significant vaginal tissue levels of dapivirine.
      However, no dapivirine was detected in cervical tissue samples using the methods
      described here. Plasma and vaginal fluid levels were lower than those in previous
      clinical studies, while there were detectable dapivirine levels in the rectal
      tissue and fluid. All tissue and fluid levels tailed off rapidly to undetectable
      levels following removal of the ring. The sheep represents a very useful model
      for the assessment of the safety and pharmacokinetics of microbicide drug
      delivery devices, such as the vaginal ring.

PMID- 25845861
TI  - Ceftazidime-avibactam activity against multidrug-resistant Pseudomonas aeruginosa
      isolated in U.S. medical centers in 2012 and 2013.
AB  - Pseudomonas aeruginosa isolates (n = 3,902) from 75 U.S. medical centers were
      tested against ceftazidime-avibactam and comparator agents by the reference broth
      microdilution method. Overall, 96.9% of the strains were susceptible (MIC, <=8
      MUg/ml) to ceftazidime-avibactam, while the rates of susceptibility for
      ceftazidime, meropenem, and piperacillin-tazobactam were 83.8, 81.9, and 78.5%,
      respectively. Multidrug-resistant and extensively drug-resistant phenotypes were
      observed in 14.9 and 8.7% of the strains, respectively, and 81.0 and 73.7% of the
      strains were susceptible to ceftazidime-avibactam, respectively.

PMID- 25845862
TI  - Ceftazidime-avibactam activity tested against Enterobacteriaceae isolates from
      U.S. hospitals (2011 to 2013) and characterization of beta-lactamase-producing
      strains.
AB  - Ceftazidime-avibactam (MIC50/90, 0.12/0.25 MUg/ml) inhibited 99.9%
      (20,698/20,709) of Enterobacteriaceae isolates at <=8 MUg/ml. This compound was
      active against resistant subsets, including ceftazidime-nonsusceptible
      Enterobacter cloacae (MIC50/90, 0.25/0.5 MUg/ml) and extended-spectrum beta
      lactamase (ESBL) phenotype isolates. An ESBL phenotype was noted among 12.4%
      (1,696/13,692 isolates from targeted species) of the isolates, including 776
      Escherichia coli (12.0% for this species; MIC50/90, 0.12/0.25 MUg/ml), 721
      Klebsiella pneumoniae (16.3%; MIC50/90, 0.12/0.25 MUg/ml), 119 Klebsiella oxytoca
      (10.3%; MIC50/90, 0.06/0.25 MUg/ml), and 80 Proteus mirabilis (4.9%; MIC50/90,
      0.06/0.12 MUg/ml) isolates. The most common enzymes detected among ESBL phenotype
      isolates from 2013 (n = 743) screened using a microarray-based assay were CTX-M
      15-like (n = 307), KPC (n = 120), SHV ESBLs (n = 118), and CTX-M-14-like (n =
      110). KPC producers were highly resistant to comparators, and ceftazidime
      avibactam (MIC50/90, 0.5/2 MUg/ml) and tigecycline (MIC50/90, 0.5/1 MUg/ml; 98.3%
      susceptible) were the most active agents against these strains. Meropenem
      (MIC50/90, <=0.06/<=0.06 MUg/ml) and ceftazidime-avibactam (MIC50/90, 0.12/0.25
      MUg/ml) were active against CTX-M-producing isolates. Other enzymes were also
      observed, and ceftazidime-avibactam displayed good activity against the isolates
      producing less common enzymes. Among 11 isolates displaying ceftazidime-avibactam
      MIC values of >8 MUg/ml, three were K. pneumoniae strains producing metallo-beta
      lactamases (all ceftazidime-avibactam MICs, >32 MUg/ml), with two NDM-1 producers
      and one K. pneumoniae strain carrying the bla(KPC-2) and bla(VIM-4) genes.
      Therapeutic options for isolates producing beta-lactamases may be limited, and
      ceftazidime-avibactam, which displayed good activity against strains, including
      those producing KPC enzymes, merits further study in infections where such
      organisms occur.

PMID- 25845863
TI  - Fast hepatitis C virus RNA elimination and NS5A redistribution by NS5A inhibitors
      studied by a multiplex assay approach.
AB  - While earlier therapeutic strategies for the treatment of hepatitis C virus (HCV)
      infection relied exclusively on interferon (IFN) and ribavirin (RBV), four direct
      acting antiviral agents (DAAs) have now been approved, aiming for an interferon
      free strategy with a short treatment duration and fewer side effects. To
      facilitate studies on the mechanism of action (MOA) and efficacy of DAAs, we
      established a multiplex assay approach, which employs flow cytometry, a Gaussia
      luciferase reporter system, Western blot analysis, reverse transcription
      quantitative PCR (RT-qPCR), a limited dilution assay (50% tissue culture
      infectious dose [TCID50]), and an image profiling assay that follows the NS5A
      redistribution in response to drug treatment. We used this approach to compare
      the relative potency of various DAAs and the kinetics of their antiviral effects
      as a potential preclinical measure of their potential clinical utility. We
      evaluated the NS5A inhibitors ledipasvir (LDV) and daclatasvir (DCV), the NS3/4A
      inhibitor danoprevir (DNV), and the NS5B inhibitor sofosbuvir (SOF). In terms of
      kinetics, our data demonstrate that the NS5A inhibitor LDV, followed closely by
      DCV, has the fastest effect on suppression of viral proteins and RNA and on
      redistribution of NS5A. In terms of MOA, LDV has a more pronounced effect than
      DCV on the viral replication, assembly, and infectivity of released virus. Our
      approach can be used to facilitate the study of the biological processes involved
      in HCV replication and help identify optimal drug combinations.

PMID- 25845864
TI  - A thorough QT study to evaluate the effects of therapeutic and supratherapeutic
      doses of delafloxacin on cardiac repolarization.
AB  - A randomized, double-blind, placebo-controlled, 4-period crossover study was
      conducted in 52 healthy adults to assess the effect of delafloxacin on the
      corrected QT (QTc) interval. The QT interval, corrected for heart rate using
      Fridericia's formula (QTcF), was determined predose and at 0.5, 1, 1.25, 1.5,
      1.75, 2, 2.5, 3, 4, 5, 6, 12, 18, and 24 h after dosing with delafloxacin at 300
      mg intravenously (i.v.; therapeutic), delafloxacin at 900 mg i.v.
      (supratherapeutic), moxifloxacin at 400 mg orally (p.o.; positive control), and
      placebo. The pharmacokinetic profile of delafloxacin was also evaluated. At each
      time point after delafloxacin administration, the upper limit of the 90%
      confidence interval (CI) for the placebo-corrected change from the predose
      baseline in QTcF (DeltaDeltaQTcF) was less than 10 ms (maximum, 3.9 ms at 18 h
      after dosing), indicating an absence of a clinically meaningful increase in the
      QTc interval. The lower limit of the 90% CI of DeltaDeltaQTcF for moxifloxacin
      versus placebo was longer than 5 ms at all 5 time points selected for assay
      sensitivity analysis, demonstrating that the study was adequately sensitive to
      assess QTc prolongation. There was no positive relationship between delafloxacin
      plasma concentrations and DeltaDeltaQTcF. Treatment-emergent adverse events (AEs)
      were more frequent among subjects receiving a single supratherapeutic dose of 900
      mg delafloxacin. There were no deaths, serious AEs, or AEs leading to study
      discontinuation and no clinically meaningful abnormalities in laboratory values
      or vital signs observed at any time point after any dose of the study drug.

PMID- 25845865
TI  - In vivo pharmacokinetic/pharmacodynamic profiles of valnemulin in an experimental
      intratracheal Mycoplasma gallisepticum infection model.
AB  - Valnemulin, a semisynthetic pleuromutilin antibiotic derivative, is greatly
      active against Mycoplasma. The objective of our study was to evaluate the
      effectiveness of valnemulin against Mycoplasma gallisepticum in a neutropenic
      intratracheal model in chickens using a pharmacokinetic/pharmacodynamic (PK-PD)
      method. The PK of valnemulin after intramuscular (i.m.) administration at doses
      of 1, 10, and 20 mg/kg of body weight in M. gallisepticum-infected neutropenic
      chickens was evaluated by liquid chromatography-tandem mass spectrometry (LC
      MS/MS). Real-time PCR (RT-PCR) was used for quantitative detection of M.
      gallisepticum. The ratio of the 24-h area under the concentration-time curve
      divided by the MIC (AUC24/MIC) correlated well with the in vivo antibacterial
      effectiveness of valnemulin (R(2) = 0.9669). The AUC24/MIC ratios for
      mycoplasmastasis (a reduction of 0 log10 color-changing unit [CCU]
      equivalents/ml), a reduction of 1 log10 CCU equivalents/ml, and a reduction of
      2.5 log10 CCU equivalents/ml are 28,820, 38,030, and 56,256, respectively. In
      addition, we demonstrated that valnemulin at a dose of 6.5 mg/kg resulted in a
      reduction of 2.5 log10 CCU equivalents/ml. These investigations provide a solid
      foundation for the usage of valnemulin in poultry with M. gallisepticum
      infections.

PMID- 25845866
TI  - Kibdelomycin is a bactericidal broad-spectrum aerobic antibacterial agent.
AB  - Bacterial resistance to antibiotics continues to grow and pose serious
      challenges, while the discovery rate for new antibiotics declines. Kibdelomycin
      is a recently discovered natural-product antibiotic that inhibits bacterial
      growth by inhibiting the bacterial DNA replication enzymes DNA gyrase and
      topoisomerase IV. It was reported to be a broad-spectrum aerobic Gram-positive
      agent with selective inhibition of the anaerobic bacterium Clostridium difficile.
      We have extended the profiling of kibdelomycin by using over 196 strains of Gram
      positive and Gram-negative aerobic pathogens recovered from worldwide patient
      populations. We report the MIC50s, MIC90s, and bactericidal activities of
      kibdelomycin. We confirm the Gram-positive spectrum and report for the first time
      that kibdelomycin shows strong activity (MIC90, 0.125 MUg/ml) against clinical
      strains of the Gram-negative nonfermenter Acinetobacter baumannii but only weak
      activity against Pseudomonas aeruginosa. We confirm that well-characterized
      resistant strains of Staphylococcus aureus and Streptococcus pneumoniae show no
      cross-resistance to kibdelomycin and quinolones and coumarin antibiotics. We also
      show that kibdelomycin is not subject to efflux in Pseudomonas, though it is in
      Escherichia coli, and it is generally affected by the outer membrane permeability
      entry barrier in the nonfermenters P. aeruginosa and A. baumannii, which may be
      addressable by structure-based chemical modification.

PMID- 25845867
TI  - Open-label, single-dose, parallel-group study in healthy volunteers to determine
      the drug-drug interaction potential between KAE609 (cipargamin) and piperaquine.
AB  - KAE609 represents a new class of potent, fast-acting, schizonticidal
      antimalarials. This study investigated the safety and pharmacokinetics of KAE609
      in combination with the long-acting antimalarial piperaquine (PPQ) in healthy
      volunteers. A two-way pharmacokinetic interaction was hypothesized for KAE609 and
      PPQ, as both drugs are CYP3A4 substrates and inhibitors. The potential for both
      agents to affect the QT interval was also assessed. This was an open-label,
      parallel-group, single-dose study with healthy volunteers. Subjects were
      randomized to four parallel dosing arms with five cohorts (2:2:2:2:1), receiving
      75 mg KAE609 plus 320 mg PPQ, 25 mg KAE609 plus 1,280 mg PPQ, 25 mg KAE609 alone,
      320 mg PPQ alone, or 1,280 mg PPQ alone. Triplicate electrocardiograms were
      performed over the first 24 h after dosing, with single electrocardiograms at
      other time points. Routine safety (up to 89 days) and pharmacokinetic (up to 61
      days) assessments were performed. Of the 110 subjects recruited, 99 completed the
      study. Coadministration of PPQ had no overall effect on exposure to KAE609,
      although 1,280 mg PPQ decreased the KAE609 maximum concentration (Cmax) by 17%.
      The group that received 25 mg KAE609 plus 1,280 mg PPQ showed a 32% increase in
      the PPQ area under the concentration-time curve from 0 to infinity (AUCinf),
      while the group that received 75 mg KAE609 plus 320 mg PPQ showed a 14%
      reduction. Mean changes from baseline in the QT interval corrected by
      Fridericia's method (QTcF) and the QT interval corrected by Bazett's method
      (QTcB) with PPQ were consistent with its known effects. PPQ but not KAE609
      exposure correlated with corrected QT interval (QTc) increases, and KAE609 did
      not affect the PPQ exposure-QTc relationship. The QTcF effect for PPQ (least
      squares estimate of the difference in mean maximal changes from baseline of 7.47
      ms [90% confidence interval, 3.55 to 11.4 ms]) was consistent with the criteria
      for a positive thorough QT study. No subject had QTcF or QTcB values of >500 ms.
      Both drugs given alone or in combination were well tolerated, with no deaths,
      serious adverse events (AEs), or severe AEs reported. Most AEs were mild; upper
      respiratory tract infections, headache, diarrhea, and oropharyngeal pain were
      most common. PPQ and KAE609 coadministration had no relevant effect on exposure
      to either agent, and KAE609 did not affect or potentiate the known effects of PPQ
      on cardiac conduction.

PMID- 25845868
TI  - Homology modeling of NAD+-dependent DNA ligase of the Wolbachia endosymbiont of
      Brugia malayi and its drug target potential using dispiro-cycloalkanones.
AB  - Lymphatic filarial nematodes maintain a mutualistic relationship with the
      endosymbiont Wolbachia. Depletion of Wolbachia produces profound defects in
      nematode development, fertility, and viability and thus has great promise as a
      novel approach for treating filarial diseases. NAD(+)-dependent DNA ligase is an
      essential enzyme of DNA replication, repair, and recombination. Therefore, in the
      present study, the antifilarial drug target potential of the NAD(+)-dependent DNA
      ligase of the Wolbachia symbiont of Brugia malayi (wBm-LigA) was investigated
      using dispiro-cycloalkanone compounds. Dispiro-cycloalkanone specifically
      inhibited the nick-closing and cohesive-end ligation activities of the enzyme
      without inhibiting human or T4 DNA ligase. The mode of inhibition was competitive
      with the NAD(+) cofactor. Docking studies also revealed the interaction of these
      compounds with the active site of the target enzyme. The adverse effects of these
      inhibitors were observed on adult and microfilarial stages of B. malayi in vitro,
      and the most active compounds were further monitored in vivo in jirds and
      mastomys rodent models. Compounds 1, 2, and 5 had severe adverse effects in vitro
      on the motility of both adult worms and microfilariae at low concentrations.
      Compound 2 was the best inhibitor, with the lowest 50% inhibitory concentration
      (IC50) (1.02 MUM), followed by compound 5 (IC50, 2.3 MUM) and compound 1 (IC50,
      2.9 MUM). These compounds also exhibited the same adverse effect on adult worms
      and microfilariae in vivo (P < 0.05). These compounds also tremendously reduced
      the wolbachial load, as evident by quantitative real-time PCR (P < 0.05). wBm
      LigA thus shows great promise as an antifilarial drug target, and dispiro
      cycloalkanone compounds show great promise as antifilarial lead candidates.

PMID- 25845869
TI  - Mutations in the bacterial ribosomal protein l3 and their association with
      antibiotic resistance.
AB  - Different groups of antibiotics bind to the peptidyl transferase center (PTC) in
      the large subunit of the bacterial ribosome. Resistance to these groups of
      antibiotics has often been linked with mutations or methylations of the 23S rRNA.
      In recent years, there has been a rise in the number of studies where mutations
      have been found in the ribosomal protein L3 in bacterial strains resistant to PTC
      targeting antibiotics but there is often no evidence that these mutations
      actually confer antibiotic resistance. In this study, a plasmid exchange system
      was used to replace plasmid-carried wild-type genes with mutated L3 genes in a
      chromosomal L3 deletion strain. In this way, the essential L3 gene is available
      for the bacteria while allowing replacement of the wild type with mutated L3
      genes. This enables investigation of the effect of single mutations in
      Escherichia coli without a wild-type L3 background. Ten plasmid-carried mutated
      L3 genes were constructed, and their effect on growth and antibiotic
      susceptibility was investigated. Additionally, computational modeling of the
      impact of L3 mutations in E. coli was used to assess changes in 50S structure and
      antibiotic binding. All mutations are placed in the loops of L3 near the PTC.
      Growth data show that 9 of the 10 mutations were well accepted in E. coli,
      although some of them came with a fitness cost. Only one of the mutants exhibited
      reduced susceptibility to linezolid, while five exhibited reduced susceptibility
      to tiamulin.

PMID- 25845870
TI  - Praziquantel in a clay nanoformulation shows more bioavailability and higher
      efficacy against murine Schistosoma mansoni infection.
AB  - Consideration of existing compounds always simplifies and shortens the long and
      difficult process of discovering new drugs specifically for diseases of
      developing countries, an approach that may add to the significant potential cost
      savings. This study focused on improving the biological characteristics of the
      already-existing antischistosomal praziquantel (PZQ) by incorporating it into
      montmorillonite (MMT) clay as a delivery carrier to overcome its known
      bioavailability drawbacks. The oral bioavailability of a PZQ-MMT clay
      nanoformulation and its in vivo efficacy against Schistosoma mansoni were
      investigated. The PZQ-MMT clay nanoformulation provided a preparation with a
      controlled release rate, a decrease in crystallinity, and an appreciable
      reduction in particle size. Uninfected and infected mice treated with PZQ-MMT
      clay showed 3.61- and 1.96-fold and 2.16- and 1.94-fold increases, respectively,
      in area under the concentration-time curve from 0 to 8 h (AUC0-8) and maximum
      concentration of drug in serum (Cmax), with a decrease in elimination rate
      constant (kel) by 2.84- and 1.35-fold and increases in the absorption rate
      constant (ka) and half-life (t1/2e) by 2.11- and 1.51-fold and 2.86- and 1.34
      fold, respectively, versus the corresponding conventional PZQ-treated groups.
      This improved bioavailability has been expressed in higher efficacy of the drug,
      where the dose necessary to kill 50% of the worms was reduced by >3-fold (PZQ 50%
      effective dose [ED50] was 20.25 mg/kg of body weight for PZQ-MMT clay compared to
      74.07 mg/kg for conventional PZQ), with significant reduction in total tissue egg
      load and increase in total immature, mature, and dead eggs in most of the drug
      treated groups. This formulation showed better bioavailability, enhanced
      antischistosomal efficacy, and a safer profile despite the longer period of
      residence in the systemic circulation. Although the conventional drug's toxicity
      was not examined, animal mortality rates were not different between groups
      receiving the test PZQ-clay nanoformulation and conventional PZQ.

PMID- 25845871
TI  - Colonization of extended-spectrum-beta-lactamase- and NDM-1-producing
      Enterobacteriaceae among pregnant women in the community in a low-income country:
      a potential reservoir for transmission of multiresistant Enterobacteriaceae to
      neonates.
AB  - The spread of extended-spectrum-beta-lactamase-producing Enterobacteriaceae (ESBL
      PE) in low-income countries, where the burden of neonatal sepsis is high, may
      have a serious impact on neonatal mortality rates. Given the potential for mother
      to-child transmission of multiresistant bacteria, this study investigated the
      ESBL-PE rectal colonization among pregnant women at delivery in the community in
      Madagascar and estimated a prevalence of 18.5% (95% confidence interval, 14.5% to
      22.6%). One strain of Klebsiella pneumoniae isolated was also a New Delhi metallo
      beta-lactamase-1 (NDM-1) producer.

PMID- 25845872
TI  - Impact of combination antimicrobial therapy on mortality risk for critically ill
      patients with carbapenem-resistant bacteremia.
AB  - There are limited treatment options for carbapenem-resistant Gram-negative
      infections. Currently, there are suggestions in the literature that combination
      therapy should be used, which frequently includes antibiotics to which the
      causative pathogen demonstrates in vitro resistance. This case-control study
      evaluated risk factors associated with all-cause mortality rates for critically
      ill patients with carbapenem-resistant Gram-negative bacteremia. Adult patients
      who were admitted to an intensive care unit with sepsis and a blood culture
      positive for Gram-negative bacteria resistant to a carbapenem were included.
      Patients with polymicrobial, recurrent, or breakthrough infections were excluded.
      Included patients were classified as survivors (controls) or nonsurvivors (cases)
      at 30 days after the positive blood culture. Of 302 patients screened, 168
      patients were included, of whom 90 patients died (53.6% [cases]) and 78 survived
      (46.4% [controls]) at 30 days. More survivors received appropriate antibiotics
      (antibiotics with in vitro activity) than did nonsurvivors (93.6% versus 53.3%; P
      < 0.01). Combination therapy, defined as multiple appropriate agents given for 48
      h or more, was more common among survivors than nonsurvivors (32.1% versus 7.8%;
      P < 0.01); however, there was no difference in multiple-agent use when in vitro
      activity was not considered (including combinations with carbapenems) (87.2%
      versus 80%; P = 0.21). After adjustment for baseline factors with multivariable
      logistic regression, combination therapy was independently associated with
      decreased risk of death (odds ratio, 0.19 [95% confidence interval, 0.06 to
      0.56]; P < 0.01). These data suggest that combination therapy with multiple
      agents with in vitro activity is associated with improved survival rates for
      critically ill patients with carbapenem-resistant Gram-negative bacteremia.
      However, that association is lost if in vitro activity is not considered.

PMID- 25845873
TI  - Pharmacokinetics of dolutegravir in a premature neonate after HIV treatment
      intensification during pregnancy.
AB  - We describe the pharmacokinetics of dolutegravir (DTG) in a premature neonate
      after maternal intensification of an antiretroviral (ARV) regimen by adding DTG.
      During the last 2 weeks of pregnancy, the ARV was tenofovir-emtricitabine,
      atazanavir-ritonavir, and DTG (50 mg once daily). From the interaction between
      atazanavir and DTG via CYP3A4 and UGT1A1 and placental efflux transporter
      inhibition and considering the infant's probable enzymatic immaturity, the DTG
      elimination half-life was estimated to be 4-fold longer in neonates than in
      adults.

PMID- 25845874
TI  - Enantiomers of nifurtimox do not exhibit stereoselective anti-Trypanosoma cruzi
      activity, toxicity, or pharmacokinetic properties.
AB  - With the aim of improving the available drugs for the treatment of Chagas
      disease, individual enantiomers of nifurtimox were characterized. The results
      indicate that the enantiomers are equivalent in their in vitro activity against a
      panel of Trypanosoma cruzi strains; in vivo efficacy in a murine model of Chagas
      disease; in vitro toxicity and absorption, distribution, metabolism, and
      excretion characteristics; and in vivo pharmacokinetic properties. There is
      unlikely to be any therapeutic benefit of an individual nifurtimox enantiomer
      over the racemic mixture.

PMID- 25845875
TI  - Clinical and microbiologic analysis of the risk factors for mortality in patients
      with heterogeneous vancomycin-intermediate Staphylococcus aureus bacteremia.
AB  - The prevalence of the heterogeneous vancomycin-intermediate Staphylococcus aureus
      (hVISA) phenotype among methicillin-resistant S. aureus (MRSA) blood isolates can
      reach 38%. hVISA bacteremia is known to be associated with vancomycin treatment
      failure, including persistent bacteremia. We conducted this study to evaluate
      risk factors for 12-week mortality in patients with hVISA bacteremia through a
      detailed clinical and microbiological analysis of a prospective cohort of
      patients with S. aureus bacteremia. All isolates were collected on the first day
      of bacteremia and subjected to population analysis profiling for hVISA detection,
      genotyping, and PCR analysis for 39 virulence factors. Of 382 patient with MRSA
      bacteremia, 121 (32%) had hVISA bacteremia. Deceased patients were more likely to
      have hematologic malignancy (P = 0.033), ultimately or rapidly fatal disease (P =
      0.007), and a higher Pitt bacteremia score (P = 0.010) than surviving patients.
      The sequence type 239 (ST239) clonal type and definitive linezolid treatment were
      associated with a trend toward reduced mortality (P = 0.061 and 0.072,
      respectively), but a high vancomycin MIC (>=2 mg/liter) was not associated with
      increased mortality (P = 0.368). In a multivariate analysis, ultimately or
      rapidly fatal disease (adjusted odds ratio [aOR], 2.80; 95% confidence interval
      [CI], 1.14 to 6.85) and a high Pitt bacteremia score (aOR, 1.26; 95% CI, 1.07 to
      1.48) were independent risk factors for mortality. Hematologic malignancy was
      associated with a trend toward increased mortality (P = 0.094), and ST239 was
      associated with a trend toward reduced mortality (P = 0.095). Our study suggests
      that ST239 hVISA is a possible predictor of survival in hVISA bacteremia.

PMID- 25845876
TI  - A pantetheinase-resistant pantothenamide with potent, on-target, and selective
      antiplasmodial activity.
AB  - Pantothenamides inhibit blood-stage Plasmodium falciparum with potencies (50%
      inhibitory concentration [IC50], ~20 nM) similar to that of chloroquine. They
      target processes dependent on pantothenate, a precursor of the essential
      metabolic cofactor coenzyme A. However, their antiplasmodial activity is reduced
      due to degradation by serum pantetheinase. Minor modification of the
      pantothenamide structure led to the identification of alpha-methyl-N-phenethyl
      pantothenamide, a pantothenamide resistant to degradation, with excellent
      antiplasmodial activity (IC50, 52 +/- 6 nM), target specificity, and low
      toxicity.

PMID- 25845877
TI  - Characterization of multiple NDM-1-producing Enterobacteriaceae isolates from the
      same patient.
AB  - A male patient was admitted to a community hospital in Ontario, Canada, with an
      infected sacral ulcer after returning from India, where he was hospitalized.
      Carbapenem-resistant Escherichia coli (isolated from blood cultures),
      Enterobacter cloacae, and Providencia stuartii (from urine samples), all positive
      for bla(NDM-1), were recovered. Comparative NDM-1 plasmid analysis suggests both
      lateral plasmid transfer and independent acquisition of the bla(NDM-1) gene in
      these clinical isolates.

PMID- 25845878
TI  - Profiling of beta-lactam selectivity for penicillin-binding proteins in
      Streptococcus pneumoniae D39.
AB  - Selective fluorescent beta-lactam chemical probes enable the visualization of the
      transpeptidase activity of penicillin-binding proteins (PBPs) at different stages
      of bacterial cell division. To facilitate the development of new fluorescent
      probes for PBP imaging, we evaluated 20 commercially available beta-lactams for
      selective PBP inhibition in an unencapsulated derivative of the D39 strain of
      Streptococcus pneumoniae. Live cells were treated with beta-lactam antibiotics at
      different concentrations and subsequently incubated with Bocillin FL (Boc-FL;
      fluorescent penicillin) to saturate uninhibited PBPs. Fluorophore-labeled PBPs
      were visualized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS
      PAGE) and fluorescence scanning. Among 20 compounds tested, carbapenems
      (doripenem and meropenem) were coselective for PBP1a, PBP2x, and PBP3, while six
      of the nine penicillin compounds were coselective for PBP2x and PBP3. In
      contrast, the seven cephalosporin compounds tested display variability in their
      PBP-binding profiles. Three cephalosporin compounds (cefoxitin, cephalexin, and
      cefsulodin) and the monobactam aztreonam exhibited selectivity for PBP3, while
      only cefuroxime (a cephalosporin) was selective for PBP2x. Treatment of S.
      pneumoniae cultures with a sublethal concentration of cefuroxime that inhibited
      60% of PBP2x activity and less than 20% of the activity of other PBPs resulted in
      formation of elongated cells. In contrast, treatment of S. pneumoniae cultures
      with concentrations of aztreonam and cefoxitin that inhibited up to 70% of PBP3
      activity and less than 30% of other PBPs resulted in no discernible morphological
      changes. Additionally, correlation of the MIC and IC50s for each PBP, with the
      exception of faropenem, amdinocillin (mecillinam), and 6-APA, suggests that
      pneumococcal growth inhibition is primarily due to the inhibition of PBP2x.

PMID- 25845879
TI  - Ibuprofen potentiates the in vivo antifungal activity of fluconazole against
      Candida albicans murine infection.
AB  - Candida albicans is the most prevalent cause of fungemia worldwide. Its ability
      to develop resistance in patients receiving azole antifungal therapy is well
      documented. In a murine model of systemic infection, we show that ibuprofen
      potentiates fluconazole antifungal activity against a fluconazole-resistant
      strain, drastically reducing the fungal burden and morbidity. The therapeutic
      combination of fluconazole with ibuprofen may constitute a new approach for the
      management of antifungal therapeutics to reverse the resistance conferred by
      efflux pump overexpression.

PMID- 25845880
TI  - Commensal streptococci serve as a reservoir for beta-lactam resistance genes in
      Streptococcus pneumoniae.
AB  - Streptococcus pneumoniae is a leading cause of pneumonia, meningitis, septicemia,
      and middle ear infections. The incidence of S. pneumoniae isolates that are not
      susceptible to penicillin has risen worldwide and may be above 20% in some
      countries. Beta-lactam antibiotic resistance in pneumococci is associated with
      significant sequence polymorphism in penicillin-binding proteins (PBPs).
      Commensal streptococci, especially S. mitis and S. oralis, have been identified
      as putative donors of mutated gene fragments. However, no studies have compared
      sequences of the involved pbp genes in large collections of commensal
      streptococci with those of S. pneumoniae. We therefore investigated the sequence
      diversity of the transpeptidase region of the three pbp genes, pbp2x, pbp2b, and
      pbp1a in 107, 96, and 88 susceptible and nonsusceptible strains of commensal
      streptococci, respectively, at the nucleotide and amino acid levels to determine
      to what extent homologous recombination between commensal streptococci and S.
      pneumoniae plays a role in the development of beta-lactam resistance in S.
      pneumoniae. In contrast to pneumococci, extensive sequence variation in the
      transpeptidase region of pbp2x, pbp2b, and pbp1a was observed in both susceptible
      and nonsusceptible strains of commensal streptococci, conceivably reflecting the
      genetic diversity of the many evolutionary lineages of commensal streptococci
      combined with the recombination events occurring with intra- and interspecies
      homologues. Our data support the notion that resistance to beta-lactam
      antibiotics in pneumococci is due to sequences acquired from commensal Mitis
      group streptococci, especially S. mitis. However, several amino acid alterations
      previously linked to beta-lactam resistance in pneumococci appear to represent
      species signatures of the donor strain rather than being causal of resistance.

PMID- 25845881
TI  - Etest cannot be recommended for in vitro susceptibility testing of mucorales.
AB  - Amphotericin B and posaconazole susceptibility patterns were determined for the
      most prevalent Mucorales, following EUCAST (European Committee on Antimicrobial
      Susceptibility Testing) broth microdilution guidelines. In parallel, Etest was
      performed and evaluated against EUCAST. The overall agreement of MICs gained with
      Etest and EUCAST was 75.1%; therefore, Etest cannot be recommended for antifungal
      susceptibility testing of Mucorales. Amphotericin B was the most active drug
      against Mucorales species in vitro, while the activities of posaconazole were
      more restricted.

PMID- 25845882
TI  - Analysis of the human osseous nasal shape--population differences and sexual
      dimorphism.
AB  - OBJECTIVES: In this study, the shape of the outer osseous nose in a German and a
      Chinese sample is analyzed using a dense set of semi-landmarks. Shape differences
      related to population and sex as well as directional and fluctuating asymmetry
      were statistically evaluated and also visualized. MATERIALS AND METHODS: Shape
      differences in the bony nose were investigated between a large sample of CT scans
      of German (140 ?, 127 ?) and Chinese (135 ?, 132 ?) crania. We used semi
      automatic methods to represent the shape of this region as a dense point-cloud,
      consisting of 370 three-dimensional bilateral coordinates. Both the symmetric and
      asymmetric modes of shape variation were addressed. RESULTS: Strong differences
      in nasal shape were found between the two populations, while sex was found to
      play a minor role in explaining the observed shape variation. The expression of
      sexual dimorphism was similar in both populations. Differences attributed to
      population affinity and to sexual dimorphism were both found to affect the shape
      of the ossa nasalia and the projection of the spina nasalis. The correlation with
      population/sex was weak for directional asymmetry, but strong for fluctuating
      asymmetry. The nasal region is more asymmetric in Germans than in Chinese, with
      males displaying more asymmetry than females in both populations. DISCUSSION:
      While the bony nose is well suited for predicting population affinity, regarding
      the populations under investigation, its value for sexing unknown individuals is
      rather moderate. The similar expression of sexual dimorphism in those otherwise
      very dissimilar populations indicates common factors responsible for these
      differences.

PMID- 25845883
TI  - Simple thiol-ene click chemistry modification of SBA-15 silica pores with
      carboxylic acids.
AB  - A straightforward approach for anchoring tailored carboxylic groups in mesoporous
      SiO2 colloidal materials is presented. The thiol-ene photochemical reaction
      between vinyltrimethoxysilane precursors and various thiocarboxylic acids which
      has, click chemistry features (i.e. high conversion yields, insensitivity to
      oxygen, mild reaction conditions), results in carboxylated silane precursors that
      can be readily used as surface modifiers. The carboxylic groups of acetic,
      undecanoic and succinic acid were immobilized on the silica mesopore walls of SBA
      15 powders employing the synthesized silane precursors. Post-grafting has been
      confirmed through infrared spectrometry (FTIR), energy dispersive X-ray
      spectroscopy (EDS), elemental analysis (EA) and zeta potential measurements.
      Detailed field-emission gun scanning electron microscopy (FESEM) images and small
      angle X-ray scattering (SAXS) data revealed parallel mesopores and ordered
      mesostructures. It is shown that the immobilized COOH groups are chemically
      accessible for acid-base reactions as well as copper adsorption. Immobilization
      of easily synthesized tailored carboxylic modified alkoxide precursors within
      mesoporous systems provides a unique chemical nanoenvironment within these
      ordered frameworks. 

PMID- 25845884
TI  - A simple way to prepare Pd/Fe3O4/polypyrrole hollow capsules and their
      applications in catalysis.
AB  - Preparation of catalysts with good catalytic activity and high stability,
      together with magnetic separation property, in a simple way is highly desirable.
      In this paper, we reported a novel strategy to construct magnetic recyclable
      hollow capsules with Pd and Fe3O4 nanoparticles embedded in polypyrrole (PPy)
      shell via only two steps: first, synthesization of Pd nanoparticles, preparation
      of Fe3O4 nanoparticles, and formation of PPy shell were finished in one-step on
      the surface of polystyrene (PS) nanospheres; then, the PS core was selectively
      removed by tetrahydrofuran. The Pd/Fe3O4/PPy hollow capsules exhibited good
      catalytic property in reduction of 4-nitrophenol with NaBH4 as reducing agent,
      and the reaction rate constants were calculated through pseudo-first-order
      reaction equation. Due to incorporation of Fe3O4 nanoparticles, the catalysts
      could be quickly separated from the reaction solution by magnet and reused
      without obvious catalytic loss. Besides catalytic property and reusability, their
      stability was also examined by HNO3 etching experiment. Compared with bare Pd and
      Fe3O4 nanoparticles, the stability of both Pd and Fe3O4 nanoparticles in hollow
      capsules was largely improved owing to the protection of PPy shell. The good
      catalytic performance, ease of separation, high stability and especially a simple
      preparation procedure, made Pd/Fe3O4/PPy hollow capsules highly promising
      candidates for diverse applications. 

PMID- 25845886
TI  - Seasonal isolation of microalgae from municipal wastewater for remediation and
      biofuel applications.
AB  - AIMS: The objective of the study was to isolate the microalgae strains from
      treated municipal wastewater in both summer and winter seasons in order to
      identify strains better suited for nutrient remediation and biofuel production
      under either cooler or warmer temperatures. METHODS AND RESULTS: Fifty-six
      strains in total were isolated and identified by DNA sequencing from effluent
      samples collected from a local wastewater treatment plant during the summer and
      winter of 2011. Screening of 41 isolates based on the fatty acid productivity at
      either 22 or 10 degrees C resulted in the selection of 12 strains organized into
      two groups of 6-the M (mild) and C (cool) groups, respectively. Four of the C
      group strains were isolated from the winter sample, while four of the M-group
      isolates were isolated from the summer sample. Fatty acid pools in M-group
      strains were heavily regulated in response to growth temperature while C-group
      strains were more insensitive. In three of the six C-group strains, the rates of
      biomass and fatty acid productivity at 10 degrees C exceeded the corresponding
      rates at 22 degrees C. Conversely, M group were always more productive at 22
      compared to 10 degrees C. Mixotrophic strategies to enhance productivity were
      generally unsuccessful in M-group strains at 22 degrees C but proved to be more
      effective in C-group cultures at 10 degrees C. CONCLUSIONS: In general, C-group
      strains appeared better suited for growth in municipal wastewater at 10 degrees
      C, while M-group strains were better suited at 22 degrees C. On balance, C-group
      isolates were more likely to come from winter wastewater samples while M-group
      strains were more likely to come from the summer sample. SIGNIFICANCE AND IMPACT
      OF THE STUDY: Our results demonstrate that the effects of temperature on
      microalgal growth for wastewater remediation can be mitigated somewhat by
      isolation and careful selection of strains adapted to seasonal wastewater
      conditions.

PMID- 25845887
TI  - Immune Response Profile against Persistent Endodontic Pathogens Candida albicans
      and Enterococcus faecalis In Vitro.
AB  - INTRODUCTION: Persistent microorganisms such as Candida albicans and Enterococcus
      faecalis might be directly related to endodontic treatment failure. The host
      response to these microorganisms impairs the reestablishment of intraradicular
      and periradicular health. METHODS: The present investigation evaluated the
      expression of inflammatory mediators produced by RAW 264.7 cells in the presence
      of heat-killed antigens (HK) C. albicans and E. faecalis. Cultures of RAW cells
      were stimulated with both antigens in the presence or absence of recombinant
      interferon (rIFN)-gamma. Parameters of cell viability, production of nitric oxide
      (NO), as well as the synthesis of interleukin (IL)-1alpha, IL-6, IL-10, IL-12,
      monocyte chemotactic protein-1, and tumor necrosis factor (TNF)-alpha were
      analyzed. RESULTS: Results demonstrated that cell viability was especially
      reduced in antigens and rIFN-gamma-stimulated groups. Groups stimulated with HK
      C. albicans upregulated IL-10 production. Otherwise, the addition of rIFN-gamma
      to HK C. albicans upregulated TNF-alpha and NO production. Groups stimulated with
      HK E. faecalis upregulated TNF-alpha production. HK E. faecalis and rIFN-gamma
      upregulated TNF-alpha and NO synthesis. The production of other cytokines
      remained unchanged by all stimuli. CONCLUSIONS: Knowledge regarding the host
      mechanism of response to microorganisms that perpetuate endodontic infection and
      the periradicular lesions can contribute to optimization of endodontic therapy.
      The mentioned inflammatory mediators and virulence factors involved in endodontic
      failure might guide lesion progression and also be targets in the development of
      disinfectant and immunomodulatory agents.

PMID- 25845888
TI  - Ruminococcal cellulosome systems from rumen to human.
AB  - A cellulolytic fiber-degrading bacterium, Ruminococcus champanellensis, was
      isolated from human faecal samples, and its genome was recently sequenced.
      Bioinformatic analysis of the R. champanellensis genome revealed numerous cohesin
      and dockerin modules, the basic elements of the cellulosome, and manual
      sequencing of partially sequenced genomic segments revealed two large tandem
      scaffoldin-coding genes that form part of a gene cluster. Representative R.
      champanellensis dockerins were tested against putative cohesins, and the results
      revealed three different cohesin-dockerin binding profiles which implied two
      major types of cellulosome architectures: (i) an intricate cell-bound system and
      (ii) a simplistic cell-free system composed of a single cohesin-containing
      scaffoldin. The cell-bound system can adopt various enzymatic architectures,
      ranging from a single enzyme to a large enzymatic complex comprising up to 11
      enzymes. The variety of cellulosomal components together with adaptor proteins
      may infer a very tight regulation of its components. The cellulosome system of
      the human gut bacterium R. champanellensis closely resembles that of the bovine
      rumen bacterium Ruminococcus flavefaciens. The two species contain orthologous
      gene clusters comprising fundamental components of cellulosome architecture.
      Since R. champanellensis is the only human colonic bacterium known to degrade
      crystalline cellulose, it may thus represent a keystone species in the human gut.

PMID- 25845889
TI  - No DDRama at chromosome ends: TRF2 takes centre stage.
AB  - Telomeres are nucleoprotein structures capping the natural termini of eukaryotic
      linear chromosomes. Telomeres possess an inherent ability to circumvent the
      activation of a full-blown DNA damage response (DDR), and hence fusion reactions,
      by limiting inappropriate double-strand break (DSB) repair and processing
      activities at eukaryotic chromosome ends. A telomere-specific protein complex,
      termed shelterin, has a crucial function in safeguarding and securing telomere
      integrity. Within this complex, TRF2 has emerged as the key player, dictating
      different states of telomere protection during the replicative lifespan of a
      cell. How TRF2 prevents activation of DSB repair activities at functional
      telomeres has now been extensively investigated. In this review we aim at
      exploring the complex and multi-faceted mechanisms underlying the TRF2-mediated
      protection of eukaryotic chromosome ends. 

PMID- 25845890
TI  - Second Opinion: Does This Patient Really Have Narcolepsy?

PMID- 25845892
TI  - OSA in Psychiatric Patients: Insomnia as a Concurrent Presentation of Autonomic
      Dysregulation in OSA.

PMID- 25845891
TI  - Chronotype and Improved Sleep Efficiency Independently Predict Depressive Symptom
      Reduction after Group Cognitive Behavioral Therapy for Insomnia.
AB  - STUDY OBJECTIVES: Cognitive behavioral therapy for insomnia (CBT-I) has been
      shown to improve both sleep and depressive symptoms, but predictors of depression
      outcome following CBT-I have not been well examined. This study investigated how
      chronotype (i.e., morningness-eveningness trait) and changes in sleep efficiency
      (SE) were related to changes in depressive symptoms among recipients of CBT-I.
      METHODS: Included were 419 adult insomnia outpatients from a sleep disorders
      clinic (43.20% males, age mean +/- standard deviation = 48.14 +/- 14.02). All
      participants completed the Composite Scale of Morningness and attended at least 4
      sessions of a 6-session group CBT-I. SE was extracted from sleep diary;
      depressive symptoms were assessed using the Beck Depression Inventory (BDI) prior
      to (Baseline), and at the end (End) of intervention. RESULTS: Multilevel
      structural equation modeling revealed that from Baseline to End, SE increased and
      BDI decreased significantly. Controlling for age, sex, BDI, and SE at Baseline,
      stronger evening chronotype and less improvement in SE significantly and uniquely
      predicted less reduction in BDI from Baseline to End. Chronotype did not predict
      improvement in SE. CONCLUSIONS: In an insomnia outpatient sample, SE and
      depressive symptoms improved significantly after a CBT-I group intervention. All
      chronotypes benefited from sleep improvement, but those with greater eveningness
      and/or less sleep improvement experienced less reduction in depressive symptom
      severity. This suggests that evening preference and insomnia symptoms may have
      distinct relationships with mood, raising the possibility that the effect of CBT
      I on depressive symptoms could be enhanced by assessing and addressing circadian
      factors.

PMID- 25845893
TI  - Does surgery for obstructive sleep apnea provide value?

PMID- 25845894
TI  - And the patient said: "let me be able to breathe and dream".

PMID- 25845895
TI  - Caffeine Awareness in Children: Insights from a Pilot Study.
AB  - STUDY OBJECTIVES: Caffeine, a commonly consumed psychoactive substance, can have
      significant effects on sleep. Caffeine intake among children is increasing,
      mainly in the form of sodas. However, adolescent caffeine consumers may lack
      knowledge about the caffeine content in common beverages. If true, this very fact
      may hamper the assessment of the effects of caffeine consumption on sleep in
      children if such assessments are a priori dependent on responders being able to
      reliably distinguish between caffeinated and noncaffeinated beverages. This
      preliminary study investigated adolescents' caffeine knowledge and intake at a
      Cleveland-area public middle school. METHODS: Seventh- and eighth-grade students
      were surveyed using: (1) the Caffeine Literacy and Sleep Study (CLASS), a 15
      question pilot instrument designed to assess caffeine knowledge and intake by
      type, quantity and timing, as well as sleep habits; and (2) the Cleveland
      Adolescent Sleepiness Questionnaire (CASQ), a validated survey measuring
      excessive daytime sleepiness in adolescents. These questionnaires were
      distributed and collected during a specified class period. RESULTS: Of the 635
      seventh- and eighth-grade students who attended school on the day of the study,
      555 (87%) participated. Lack of knowledge about caffeine content of particular
      drinks was noted in seventh and eighth graders of both sexes with nearly 29%
      unaware that their favorite drinks contain caffeine and more than 50% unable to
      correctly identify the drinks with the most caffeine. A low percentage of
      students correctly identified light-colored sodas lacking caffeine: 7-Up (24.1%),
      Sierra Mist (38.9%), ginger ale (39.8%), Sprite (39.8%), and Fresca (53.7%). The
      percentages of students correctly identifying caffeinated light-colored beverages
      were: Arizona Green Tea (43.5%), Mello Yellow (50.9%), and A&W cream soda
      (67.6%). However, Mountain Dew was correctly identified by most (93.5%) as
      caffeinated. CONCLUSIONS: Students were not consistently able to identify
      caffeine content or lack thereof in some common beverages. The results of this
      pilot study show that caffeine literacy in adolescents warrants further
      investigation and educational intervention.

PMID- 25845896
TI  - Among Metabolic Factors, Significance of Fasting and Postprandial Increases in
      Acyl and Desacyl Ghrelin and the Acyl/Desacyl Ratio in Obstructive Sleep Apnea
      before and after Treatment.
AB  - STUDY OBJECTIVES: There are reports suggesting that obstructive sleep apnea (OSA)
      may itself cause weight gain. However, recent reports showed increases in body
      mass index (BMI) following continuous positive airway pressure (CPAP) treatments.
      When considering weight changes, changes in humoral factors that have significant
      effects on appetite such as acyl (AG) and desacyl ghrelin (DAG), leptin, insulin,
      and glucose and their interactions, examples of which are AG/DAG and AG/insulin,
      are important. The aim of this study was to test the hypothesis that some
      appetite-related factors had a specific profile before and after CPAP treatment.
      METHODS: Metabolic parameters were measured cross-sectionally while fasting and
      30, 60, 90, and 120 min following breakfast in no or mild OSA (apnea-hypopnea
      index < 15, n = 15) and moderate-to-severe OSA (apnea-hypopnea index >= 15, n =
      39) participants in a single institute. There were no differences in age, sex,
      BMI, or visceral fat accumulation between the two groups. Twenty-one patients
      with moderate-to-severe OSA who received CPAP treatment also prospectively
      underwent the same testing following 3 months of CPAP treatment. RESULTS:
      Although fasting and postprandial glucose, insulin, and leptin levels did not
      differ between no or mild OSA and moderate-to-severe OSA participants, AG and
      DAG, including AG/DAG and AG/insulin, under fasting and postprandial conditions
      were significantly increased in the moderate-to-severe OSA patients (p < 0.01).
      After 3 months of CPAP treatment in 21 of the moderate-to-severe OSA
      participants, AG/DAG did not change significantly, but other ghrelin-related
      parameters including AG/insulin significantly decreased compared with values
      before treatment but remained higher than in no or mild OSA. CONCLUSION: Among
      several important metabolic factors, ghrelin-related factors had the strongest
      associations with moderate-to-severe OSA. These results indicate that continuous
      changes in ghrelin secretion in OSA patients existed at least within 3 months of
      CPAP treatment. Methods to prevent OSA as well as treatment in its early stage
      may be recommended.

PMID- 25845897
TI  - Oral Appliance Treatment Response and Polysomnographic Phenotypes of Obstructive
      Sleep Apnea.
AB  - STUDY OBJECTIVES: Mandibular advancement splints (MAS) are an effective treatment
      for obstructive sleep apnea (OSA); however, therapeutic response is variable.
      Younger age, female gender, less obesity, and milder and supine-dependent OSA
      have variably been associated with treatment success in relatively small samples.
      Our objective was to utilize a large cohort of MAS treated patients (1) to
      compare efficacy across patients with different phenotypes of OSA and (2) to
      assess demographic, anthropometric, and polysomnography variables as treatment
      response predictors. METHODS: Retrospective analysis of MAS-treated patients
      participating in clinical trials in sleep centers in Sydney, Australia between
      years 2000-2013. All studies used equivalent customized two-piece MAS devices and
      treatment protocols. Treatment response was defined as (1) apnea-hypopnea index
      (AHI) < 5/h, (2) AHI < 10/h and >= 50% reduction, and (3) >= 50% AHI reduction.
      RESULTS: A total of 425 patients (109 female) were included (age 51.2 +/- 10.9
      years, BMI 29.2 +/- 5.0 kg/m2). MAS reduced AHI by 50.3% +/- 50.7% across the
      group. Supine-predominant OSA patients had lower treatment response rates than
      non-positional OSA (e.g., 36% vs. 59% for AHI < 10/h). REM-predominant OSA showed
      a lower response rate than either NREM or non-stage dependent OSA. In prediction
      modelling, age, baseline AHI, and anthropometric variables were predictive of MAS
      treatment outcome but not OSA phenotype. Gender was not associated with treatment
      outcome. CONCLUSION: Lower MAS treatment response rates were observed in supine
      and REM sleep. In a large sample, we confirm that demographic, anthropometric,
      and polysomnographic data only weakly inform about MAS efficacy, supporting the
      need for alternative objective prediction methods to reliably select patients for
      MAS treatment.

PMID- 25845898
TI  - Nightmares: Under-Reported, Undetected, and Therefore Untreated.
AB  - OBJECTIVE: Nightmares are a robust and modifiable predictor of increased
      suicidality and poor psychiatric outcomes, yet nightmare screening and treatment
      remain rare, even in sleep centers. This paper aims to examine what proportion of
      nightmare sufferers have discussed nightmares with a healthcare provider, as well
      as possible explanations for low rates of nightmare complaints. METHODS: The
      present study utilized a large United States community sample recruited through
      mTurk and a student sample recruited from a large public university in the
      Southeast United States. In Study 1, participants (n = 809) were asked whether
      they had discussed nightmares with a healthcare provider. In Study 2 participants
      (n = 747) were asked whether they believed nightmares were treatable in addition
      to whether or not they had discussed nightmares with a healthcare provider.
      RESULTS: Of the participants in Study 1 experiencing clinically significant
      nightmare symptoms only 37.8% of participants reported discussing their
      nightmares with a healthcare professional. In Study 2 only 11.1% of participants
      with significant nightmares reporting having told a healthcare provider about
      their nightmares. Further, of these individuals with clinically significant
      nightmare symptoms, less than one-third believed that nightmares were treatable.
      Higher nightmare severity was associated with a greater likelihood of reporting
      nightmares to a healthcare physician as well as with lower beliefs that
      nightmares are treatable. CONCLUSIONS: Our findings suggest that nightmares are
      rarely reported to healthcare providers, which may explain the underutilization
      of nightmare treatments. Given the poor outcomes associated with nightmares,
      nightmare screening is warranted.

PMID- 25845899
TI  - A 27-Year-Old Female on Chronic Opioid Therapy.

PMID- 25845901
TI  - Nonrapid Eye Movement-Predominant Obstructive Sleep Apnea: Detection and
      Mechanism.
AB  - STUDY OBJECTIVES: Obstructive sleep apnea (OSA) can be severe and present in
      higher numbers during rapid eye movement (REM) than nonrapid eye movement (NREM)
      sleep; however, OSA occurs in NREM sleep and can be predominant. In general,
      ventilation decreases an average 10% to 15% during transition from wakefulness to
      sleep, and there is variability in just how much ventilation decreases. As
      dynamic changes in ventilation contribute to irregular breathing and breathing
      during NREM sleep is mainly under chemical control, our hypothesis is that
      patients with a more pronounced reduction in ventilation during the transition
      from wakefulness to NREM sleep will have NREM- predominant rather than REM
      predominant OSA. METHODS: A retrospective analysis of 451 consecutive patients
      (apnea-hypopnea index [AHI] > 5) undergoing diagnostic polysomnography was
      performed, and breath-to-breath analysis of the respiratory cycle duration, tidal
      volume, and estimated minute ventilation before and after sleep onset were
      examined. Values were calculated using respiratory inductance plethysmography.
      The correlation between the percent change in estimated minute ventilation during
      wake-sleep transitions and the percentage of apnea-hypopneas in NREM sleep (%AHI
      in NREM; defined as (AHI-NREM) / [(AHI-NREM) + (AHI-REM)] * 100) was the primary
      outcome. RESULTS: The decrease in estimated minute ventilation during wake-sleep
      transitions was 15.0 +/- 16.6% (mean +/- standard deviation), due to a decrease
      in relative tidal volume. This decrease in estimated minute ventilation was
      significantly correlated with %AHI in NREM (r = -0.222, p < 0.01). CONCLUSIONS: A
      greater dynamic reduction in ventilation back and forth from wakefulness to sleep
      contributes to the NREM predominant OSA phenotype via induced ventilatory
      instability.

PMID- 25845900
TI  - Obstructive Sleep Apnea and Kidney Disease: A Potential Bidirectional
      Relationship?
AB  - Chronic kidney disease (CKD) is associated with high mortality rates and heavy
      economic and social burdens. Nearly 10% of the United States population suffer
      from CKD, with fatal outcomes increased by 16-40 times even before reaching end
      stage renal disease. The prevalence of obstructive sleep apnea (OSA) is between
      3% and 7% in the general population, and has increased dramatically during the
      last 2 decades along with increased rates of obesity. However, the prevalence of
      OSA is much greater in patients with CKD. In addition, aggressive dialysis
      improves OSA. The current literature suggests a bidirectional association between
      CKD and OSA through a number of potential pathological mechanisms, which increase
      the possibility of both diseases being possible risk factors for each other. CKD
      may lead to OSA through a variety of mechanisms, including alterations in
      chemoreflex responsiveness, pharyngeal narrowing due to fluid overload, and
      accumulation of uremic toxins. It is also being increasingly recognized that OSA
      can also accelerate loss of kidney function. Moreover, animals exposed to
      intermittent hypoxia suffer histopathological renal damage. Potential mechanisms
      of OSA-associated renal dysfunction include renal hypoxia, hypertension,
      endothelial dysfunction, activation of the sympathetic nervous system, and
      increased oxidative stress.

PMID- 25845902
TI  - Psychometric Properties of the Pittsburgh Sleep Quality Index (PSQI) in a Cohort
      of Peruvian Pregnant Women.
AB  - STUDY OBJECTIVES: We sought to evaluate the construct validity and factor
      structure of the Spanish-language version of the Pittsburgh Sleep Quality Index
      (PSQI) among pregnant Peruvian women. METHODS: A cohort of 642 women were
      interviewed at <= 16 weeks of gestation. During interview, we ascertained
      information about lifestyles, demographics, sleep characteristics, and mood
      symptoms. Stress induced sleep disturbance, depressive symptoms, and anxiety
      symptoms were evaluated using the Ford Insomnia Response to Stress Test (FIRST),
      Patient Health Questionnaire-9 (PHQ-9), and Generalized Anxiety Disorder-7 (GAD
      7) assessment scales, respectively. Consistency indices, exploratory and
      confirmatory factor analyses, correlations, and logistic regressions were used.
      RESULTS: Both exploratory and confirmatory factor analyses indicated a three
      factor solution: sleep quality, sleep efficiency, and sleep medication. We
      observed significantly positive correlations of the PSQI with the FIRST (0.42),
      the PHQ-9 (0.49), and the GAD-7 (0.46). Poor sleepers (PSQI global score > 5) had
      significantly increased odds of experiencing stress-induced sleep disturbance
      (odds ratio, OR = 3.57; 95% CI: 2.40, 5.31), depression (OR = 5.48; 95% CI: 3.58,
      8.37), and generalized anxiety disorder (OR = 4.57; 95% CI: 3.08, 6.76).
      CONCLUSION: The Spanish-language version of the PSQI instrument was found to have
      good construct validity among pregnant Peruvian women. Consistent with some other
      studies, the PSQI was found to have a three-factor structure. Further assessment
      and validation studies are needed to determine whether the three, factor-specific
      scoring of the PSQI is favored over the PSQI global score in diverse populations.

PMID- 25845903
TI  - The effect of physician continuing medical education on patient-reported outcomes
      for identifying and optimally managing obstructive sleep apnea.
AB  - STUDY OBJECTIVE: To evaluate the effect of continuing medical education (CME)
      activities on patient reported outcomes with regard to (1) screening for
      excessive sleepiness (ES) and obstructive sleep apnea (OSA) and (2) appropriate
      referral and treatment. METHODS: A total of 725 patients were recruited from 75
      providers who either participated or did not participate in Transtheoretical
      Model (TTM)-based OSA CME activities. Patient reported outcomes from
      participating (n = 36) and non-participating providers (n = 39) were compared
      using generalized estimating equations examining random effects of provider as
      unit of assignment. RESULTS: Patients' reports demonstrate that participating
      physicians were 1.7 times more likely to initiate discussion of sleep problems
      than non-participating physicians (t1,411 = 3.71, p = 0.05) and 2.25-2.86 times
      more likely to administer validated measures for OSA (Epworth Sleepiness Scale
      and STOP-BANG). Patient reports also indicated that participating clinicians
      (79.9%) were significantly more likely to recommend seeing a sleep specialist
      compared to non-participating clinicians (60.7%; t1,348 = 9.1, p < 0.01, OR =
      2.6). Furthermore, while 89.4% of participating clinicians recommended a sleep
      study, only 73.2% of the non-participating physicians recommended one (t1,363 =
      11.46, p < 0.001, OR = 3.1). CONCLUSIONS: Participation in TTM-based OSA CME
      activities was associated with improved patient reported outcomes compared to the
      non-participating clinicians.

PMID- 25845904
TI  - STAR syndrome is part of the differential diagnosis of females with anorectal
      malformations.

PMID- 25845905
TI  - Product stability and sequestration mechanisms in Solanum tuberosum engineered to
      biosynthesize high value ketocarotenoids.
AB  - To produce commercially valuable ketocarotenoids in Solanum tuberosum, the 4, 4'
      beta-oxygenase (crtW) and 3, 3' beta-hydroxylase (crtZ) genes from Brevundimonas
      spp. have been expressed in the plant host under constitutive transcriptional
      control. The CRTW and CRTZ enzymes are capable of modifying endogenous plant
      carotenoids to form a range of hydroxylated and ketolated derivatives. The host
      (cv. Desiree) produced significant levels of nonendogenous carotenoid products in
      all tissues, but at the apparent expense of the economically critical metabolite,
      starch. Carotenoid levels increased in both wild-type and transgenic tubers
      following cold storage; however, stability during heat processing varied between
      compounds. Subcellular fractionation of leaf tissues revealed the presence of
      ketocarotenoids in thylakoid membranes, but not predominantly in the
      photosynthetic complexes. A dramatic increase in the carotenoid content of
      plastoglobuli was determined. These findings were corroborated by microscopic
      analysis of chloroplasts. In tuber tissues, esterified carotenoids, representing
      13% of the total pigment found in wild-type extracts, were sequestered in
      plastoglobuli. In the transgenic tubers, this proportion increased to 45%, with
      esterified nonendogenous carotenoids in place of endogenous compounds.
      Conversely, nonesterified carotenoids in both wild-type and transgenic tuber
      tissues were associated with amyloplast membranes and starch granules. 

PMID- 25845906
TI  - National Institutes of Health Stroke Scale score is an unreliable predictor of
      perfusion deficits in acute stroke.
AB  - BACKGROUND: Perfusion-weighted magnetic resonance imaging is not routinely used
      to investigate stroke/transient ischemic attack. Many clinicians use perfusion
      weighted magnetic resonance imaging selectively in patients with more severe
      neurological deficits, but optimal selection criteria have never been identified.
      AIMS AND/OR HYPOTHESIS: We tested the hypothesis that a National Institutes of
      Health Stroke Scale score threshold can be used to predict the presence of
      perfusion-weighted magnetic resonance imaging deficits in patients with acute
      ischemic stroke/transient ischemic attack. METHODS: National Institutes of Health
      Stroke Scale scores were prospectively assessed in 131 acute stroke/transient
      ischemic attack patients followed by magnetic resonance imaging, including
      perfusion-weighted magnetic resonance imaging within 72 h of symptom onset.
      Patients were dichotomized based on the presence or absence of perfusion deficits
      using a threshold of Tmax (time to peak maps after the impulse response) delay
      >=four-seconds and a hypoperfused tissue volume of >=1 ml. RESULTS: Patients with
      perfusion deficits (77/131, 59%) had higher median (interquartile range) National
      Institutes of Health Stroke Scale scores (8 [12]) than those without perfusion
      deficits (3 [4], P < 0.001). A receiver operator characteristic analysis
      indicated poor to moderate sensitivity of National Institutes of Health Stroke
      Scale scores for predicting perfusion deficits (area under the curve = 0.787). A
      National Institutes of Health Stroke Scale score of >=6 was associated with
      specificity of 85%, but sensitivity of only 69%. No National Institutes of Health
      Stroke Scale score threshold identified all cases of perfusion-weighted magnetic
      resonance imaging deficits with sensitivity >94%. CONCLUSIONS: Although higher
      National Institutes of Health Stroke Scale scores are predictive of perfusion
      deficits, many patients with no clinically detectable signs have persisting
      cerebral blood flow changes. A National Institutes of Health Stroke Scale score
      threshold should therefore not be used to select patients for perfusion-weighted
      magnetic resonance imaging. Perfusion-weighted magnetic resonance imaging should
      be considered in all patients presenting with acute focal neurological deficits,
      even if these deficits are transient.

PMID- 25845907
TI  - Can Dynamic Spectral Imaging System colposcopy replace conventional colposcopy in
      the detection of high-grade cervical lesions?
AB  - The sensitivity of conventional colposcopy for the detection of high-grade
      cervical lesions (cervical intraepithelial neoplasia stage 2 or above; CIN2+) is
      poor. We aimed to investigate if a Dynamic Spectral Imaging System (DySIS) can
      enhance or replace conventional colposcopy in clinical practice. From 3 December
      2013 to 29 January 2014 a total of 239 women were included. All women were
      referred to the Department of Obstetrics and Gynecology, Aarhus, Denmark because
      of an abnormal cytology result. Every woman had three to five cervical punch
      biopsies taken; two biopsies were taken following DySIS recommendations.
      Subsequent biopsies were taken following the clinician's assessment or randomly.
      DySIS allowed detection of five CIN2+ cases (7.4%) that would not have been
      detected otherwise, but it failed to detect 46 of CIN2+ cases (67.6%). The
      sensitivity and specificity of DySIS for detecting CIN2+ was 32.4 and 83.0%,
      respectively. DySIS colposcopy seemed inferior to conventional colposcopy in
      detecting high-grade lesions and cannot replace conventional colposcopy with
      random biopsies. 

PMID- 25845908
TI  - Characteristics of caring self-efficacy in pediatric nurses: a qualitative study.
AB  - PURPOSE: The present study was conducted to clarify pediatric nurses'
      characteristics of caring self-efficacy. DESIGN AND METHODS: This study was
      conducted using a qualitative content analysis approach. The participants
      included 27 pediatric nurses and clinical instructors, selected purposively. Data
      were collected using semi-structured interviews and were analyzed using the
      content analysis method. RESULTS: Data analysis generated four main themes as
      attributes of a self-efficient pediatric nurse including: (a) professional
      communications; (b) management of care; (c) altruism; and (d) proficiency.
      PRACTICE IMPLICATIONS: Nursing managers and instructors can use these results to
      help develop nurses' empowerment and self-efficacy, especially in pediatric care.

PMID- 25845909
TI  - Universality of Oxime K203 for Reactivation of Nerve Agent-Inhibited AChE.
AB  - Oxime K203 seems to be the most promising oxime in case of reactivation of tabun
      inhibited acetylcholinesterase (AChE). Although it was originally developed for
      treatment of tabun intoxications, it is able to reactivate cholinesterases
      inhibited by other nerve agents. This study is aimed at the evaluation of its
      potency in vitro against other nerve agents. For this purpose, sarin, tabun,
      cyclosarin, soman, VX, Russian VX and DFP were selected as members of the nerve
      agent family to check its universality. At high concentrations (10(-3) M), oxime
      K203 reached promising reactivation activity. At low concentrations, relevant for
      human use (10(-5) M), promising reactivation potency was obtained only with
      tabun. In conclusion, oxime K203 reactivates other nerve agents-inhibited
      cholinesterases, however its broad-spectrum reactivation is limited at high, for
      human not attainable, concentrations only.

PMID- 25845910
TI  - Analysis of gene expression profiles associated with glioma progression.
AB  - The present study aimed to investigate changes at the transcript level that are
      associated with spontaneous astrocytoma progression, and further, to discover
      novel targets for glioma diagnosis and therapy. GSE4290 microarray data
      downloaded from Gene Expression Omnibus were used to identify the differentially
      expressed genes (DGEs) by significant analysis of microarray (SAM). The Short
      Time Series Expression Miner (STEM) method was then applied to class these DEGs
      based on their degrees of differentiation in the process of tumor progression.
      Finally, EnrichNet was used to perform the Kyoto Encyclopedia of Genes and
      Genomes (KEGG) pathway enrichment analysis based on a protein-protein interaction
      (PPI) network. A total of 4,506 DEGs were detected, and the number of DEGs was
      the highest in grade IV cells (2,580 DEGs). These DEGs were classified into nine
      clusters by the STEM method. In total, 11 KEGG pathways with XD-scores larger
      than the threshold (0.96) were obtained. The DEGs enriched in pathways 1
      (extracellular matrix-receptor interaction), 3 (phagosome) and 6 (type I diabetes
      mellitus) mainly belonged to cluster 5. Pathway 2 (long-term potentiation), 4
      (Vibrio cholerae infection) and 5 (epithelial cell signaling in Helicobacter
      pylori infection) was involved with DEGs that belonged to different clusters.
      Significant changes in gene expression occurred during glioma progression.
      Pathways 1, 3 and 6 may be important for the deterioration of glioma into
      glioblastoma, and pathways 2, 4 and 5 may have a role at each stage during glioma
      progression. The associated DEGs, including SV2, NMDAR and mGluRs, may be
      suitable as biomarkers or therapeutic targets for gliomas.

PMID- 25845912
TI  - "Toothbrush" the Feet: A Periodic Mechanical Stimulus for Healing of a Severe
      Chronic Leg Ulcer.
AB  - Chronic wounds develop when the sequence of healing events are disrupted, usually
      in patients with underlying diseases such as diabetes mellitus, venous
      insufficiency, peripheral artery disease, and neuropathies and they affect most
      often the lower extremities. We present a 68-year-old woman with plantar
      ulceration, lasting for approximately 18 months, resistant to healing with
      conventional therapy and various modalities we used. The patient had a long
      history of seronegative enteropathic arthritis, Crohn's disease, secondary
      fibrillar amyloidosis, multiplex neuropathy, and small vessel vasculitis, the
      latter being the trigger event for the ulceration of her right foot. Before the
      decision for a final surgical intervention, we implemented a mechanical periodic
      stimulus using a soft toothbrush, which resulted in the gradual and complete
      healing of the ulcer within a period of 6 weeks. Patient's history and previous
      treatments are presented along with the procedures that led to the healing of the
      chronic wound. This report supports the idea that periodic mechanical stimulus is
      of great importance for the healing process and this could be the mechanism of
      action of some other methods that have been described in the medical literature. 

PMID- 25845911
TI  - Remission of systemic lupus erythematosus disease activity with regulatory
      cytokine interleukin (IL)-35 in Murphy Roths Large (MRL)/lpr mice.
AB  - The immunological mechanisms mediated by regulatory cytokine interleukin (IL)-35
      are unclear in systemic lupus erythematosus (SLE). We investigated the frequency
      of CD4(+) CD25(+) forkhead box protein 3 (FoxP3)(+) regulatory T (Treg ) and IL
      10(+) regulatory B (Breg ) cells and related immunoregulatory mechanisms in a
      female Murphy Roths Large (MRL)/lpr mouse model of spontaneous lupus-like
      disease, with or without IL-35 treatment. A remission of histopathology
      characteristics of lupus flare and nephritis was observed in the MRL/lpr mice
      upon IL-35 treatment. Accordingly, IL-35 and IL-35 receptor subunits (gp130 and
      IL-12Rbeta2) and cytokines of MRL/lpr and BALB/c mice (normal controls) were
      measured. The increased anti-inflammatory cytokines and decreased proinflammatory
      cytokines were possibly associated with the restoration of Treg and Breg
      frequency in MRL/lpr mice with IL-35 treatment, compared to phosphate-buffered
      saline (PBS) treatment. mRNA expressions of Treg -related FoxP3, IL-35 subunit
      (p35 and EBI3) and soluble IL-35 receptor subunit (gp130 and IL12Rbeta2) in
      splenic cells were up-regulated significantly in IL-35-treated mice. Compared
      with the PBS treatment group, IL-35-treated MRL/lpr mice showed an up-regulation
      of Treg -related genes and the activation of IL-35-related intracellular Janus
      kinase/signal transducer and activator of transcription signal pathways, thereby
      indicating the immunoregulatory role of IL-35 in SLE. These in vivo findings may
      provide a biochemical basis for further investigation of the regulatory
      mechanisms of IL-35 for the treatment of autoimmune-mediated inflammation. 

PMID- 25845913
TI  - What is the right timing for ultrasound evaluation after pregnancy termination
      with mifepristone?
AB  - OBJECTIVE: To determine the timing for ultrasound evaluation after medical
      termination of pregnancy (MTOP). STUDY DESIGN: The records of 301 consecutive
      women who underwent MTOP between July 2010 and July 2011 were studied
      retrospectively. The follow-up protocol included ultrasound evaluation 2 weeks
      after MTOP. Surgical termination was offered when pregnancy was found to be
      ongoing, and either hysteroscopy/curettage or a repeat ultrasound 2 weeks later
      was offered when the ultrasound findings were suspicious for retained products of
      conception. Pathology reports were used to confirm the presence of retained
      products of conception. RESULTS: Women with ultrasound findings suspicious for
      retained products of conception were significantly older than women with negative
      ultrasound findings (30.9+/-7.7 years vs 24.8+/-6 years, p<0.0001). Two weeks
      after MTOP, ultrasound findings were negative in 236 women and suspicious in 66
      women. This rate declined as the interval between ultrasound evaluation and MTOP
      increased (up to 10 weeks). Of the 18 women (5.98%) who underwent
      hysteroscopy/curettage, pathology reports indicated that 15 (83.3%) had true
      residua. CONCLUSIONS: At 2 weeks after MTOP, ultrasound findings suspicious for
      retained products of conception do not conclusively indicate failure of the
      procedure. Ultrasound evaluation should be repeated 4-6 weeks later (6-8 weeks
      after MTOP) in women with suspected residua before diagnosing failure of the
      procedure.

PMID- 25845914
TI  - Antidepressants during pregnancy and postpartum hemorrhage: a systematic review.
AB  - The use of antidepressants in pregnancy is increasing. Concerns have risen about
      the use of antidepressants during pregnancy and the risk of postpartum hemorrhage
      (PPH). The aim of this systematic review is to summarize evidence on the
      association between use of antidepressants during pregnancy and the risk of PPH.
      An Embase and Pubmed search was conducted. English and Dutch language studies
      reporting original data regarding bleeding after delivery associated with
      exposure to antidepressants during pregnancy were selected. Quality appraisal was
      conducted using the Newcastle Ottawa Scale (NOS). Out of 81 citations, 4 studies
      were included. Based on the NOS, 3 were considered of good quality and 1 was
      considered of satisfactory quality. Two studies reported an increased incidence
      of PPH in women who used antidepressants during pregnancy. The other two studies
      identified no overall increased risk of PPH among pregnant women exposed to
      antidepressants. The existing evidence remains inconclusive whether use of
      antidepressants during pregnancy is associated with an increased risk of
      postpartum hemorrhage. If there is such an association the absolute increased
      risk will be low and the clinical relevance needs to be further examined. 

PMID- 25845915
TI  - Development of the nasolacrimal apparatus in the Mongolian gerbil (Meriones
      unguiculatus), with notes on network topology and function.
AB  - The nasolacrimal apparatus (NLA) is a multicomponent functional system comprised
      of multiple orbital glands (up to four larger multicellular exocrine structures),
      a nasal chemosensory structure (vomeronasal organ: VNO), and a connecting duct
      (nasolacrimal duct: NLD). Although this system has been described in all tetrapod
      vertebrate lineages, albeit not always with all three main components present,
      considerably less is known about its ontogeny. The Mongolian gerbil (Meriones
      unguiculatus) is a common lab rodent in which the individual components of the
      adult NLA have been well studied, but as yet nothing is known about the ontogeny
      of the NLA. In this study, serial sections of 15 fetal and three adult Mongolian
      gerbil heads show that the development of the NLA falls into three fetal stages:
      inception (origin of all features), elongation (lengthening of all features), and
      expansion (widening of all features). No postnatal or juvenile specimens were
      observed in this study, but considerable growth evidently occurs before the final
      adult condition is reached. The development of the orbital glands and the VNO in
      the Mongolian gerbil is largely consistent with those in other mammals, despite a
      slight nomenclatural conundrum for the anterior orbital glands. However, the
      Mongolian gerbil NLD follows a more circuitous route than in other tetrapods, due
      mainly to the convoluted arrangement of the narial cartilages, the development of
      a pair of enlarged incisors as well as an enlarged infraorbital foramen. The
      impact of these associated features on the ontogeny and phylogeny of the NLA
      could be examined through the approach of network science. This approach allows
      for the incorporation of adaptations to specific lifestyles as potential
      explanations for the variation observed in the NLA across different tetrapod
      clades.

PMID- 25845916
TI  - How reliable are field-derived biomagnification factors and trophic magnification
      factors as indicators of bioaccumulation potential? Conclusions from a case study
      on per- and polyfluoroalkyl substances.
AB  - This review examines the usefulness of the metrics BMF (biomagnification factor)
      and TMF (trophic magnification factor), derived from field measurements of the
      levels of contaminants in naturally occurring biota, for characterizing the
      bioaccumulation potential ("B") of chemicals. Trophic magnification factor and
      BMF values greater than 1.0 are often considered to be the most conclusive
      indicators of B status, and the TMF criterion has been referred to as the "gold
      standard" for B categorization. Although not wishing to dispute the theoretical
      primacy of field-derived BMFs and TMFs as B metrics, we make the case that, in
      practice, the study-to-study (and even within-study) variability of the results
      is so great that they are of very restricted usefulness for assessing B status,
      at least in the case of the per- and polyfluoroalkyl substances (PFASs), on which
      we focus here. This conclusion is based on an analysis of the results of 24 peer
      reviewed studies reporting field-derived BMFs or TMFs for 14 PFASs, for which BMF
      values often range over several orders of magnitude from <<1.0 to >>1.0,
      sometimes even in the same study. For TMFs, the range is a factor of
      approximately 20 for the most intensely studied PFASs (perfluorooctanoic acid
      [PFOA] and perfluorooctanesulfonic acid [PFOS]). We analyze the possible causes
      for such variability: To some extent it results from the differing ways in which
      the metrics are expressed, but most of the scatter is likely attributable to such
      factors as nonachievement of the tacitly assumed steady-state conditions,
      uncertainties in the feeding ecology, the impact of metabolism of precursor
      compounds, and so forth. As more trustworthy alternatives to field-derived BMFs
      and TMFs, we suggest the implementation of dietary BMF studies performed under
      strictly controlled conditions on aquatic, terrestrial, and avian species, as
      well as the consideration of measured elimination half-lives, which have been
      demonstrated to be directly related to BMF values.

PMID- 25845917
TI  - Health and Economic Outcomes Associated with Use of an Antimicrobial Envelope as
      a Standard of Care for Cardiac Implantable Electronic Device Implantation.
AB  - INTRODUCTION: Infection of cardiac implanted electrical devices (CIED) is a
      problem. In selected patients, use of an "antibacterial envelope" (AIGISRx(r)) is
      associated with low CIED infection rates. The value of this device when used as a
      standard of care is unclear. METHODS AND RESULTS: Retrospective analysis of all
      patients (N = 1,476) who underwent CIED implantation at a single hospital. During
      the study period, some implanters used the AIGISRx as a standard of care (Yes
      AIGISRx Group, N = 365), whereas others did not use it at all (No-AIGISRx Group,
      N = 1,111). A risk score based on preoperative factors was calculated for each
      patient. Rates of CIED infection within 6 months were measured, and associated
      costs were estimated. The Yes-AIGISRx and No-AIGISRx groups had similar
      preoperative infection risk. In the No-AIGISRx group, 19 infections were observed
      (1.7%), versus 0 in the Yes-AIGISRx group (P = 0.006). The 6-month mortality rate
      among patients with infection was significantly greater than among those without
      infection (15.7% vs. 4.5%, P = 0.021). The average hospital duration for
      infection care was 13 days. By extrapolating the infection rate and costs
      observed in the No-AIGISRx group to the Yes-AIGISRx group, we estimated that
      there would have been 6.2 additional infections costing approximately $340,000.
      This cost was similar to the actual cost of the devices in the Yes-AIGISRx group,
      estimated at $320,000. CONCLUSIONS: Standard of care use of an antibacterial
      envelope as a standard of care was associated with a significantly lower rate of
      CIED infection, and appeared to be economically reasonable. Prospective trials to
      address these findings may be worthwhile.

PMID- 25845918
TI  - Abdominal pain endpoints currently recommended by the FDA and EMA for adult
      patients with irritable bowel syndrome may not be reliable in children.
AB  - BACKGROUND: The Food and Drug Administration (FDA) recommended >=30% decrease on
      patient-reported outcomes for pain be considered clinically significant in
      clinical trials for adults with irritable bowel syndrome. This percent change
      approach may not be appropriate for children. We compared three alternate
      approaches to determining clinically significant reductions in pain among
      children. METHODS: 80 children with functional abdominal pain participated in a
      study of the efficacy of amitriptyline. Endpoints included patient-reported
      estimates of feeling better, and pain Visual Analog Scale (VAS). The minimum
      clinically important difference in pain report was calculated as (i) mean change
      in VAS score for children reporting being 'better'; (ii) percent changes in pain
      (>=30% and >=50%) on the VAS; and (iii) statistically reliable changes on the VAS
      for 68% and 95% confidence intervals. KEY RESULTS: There was poor agreement
      between the three approaches. 43.6% of the children who met the FDA >=30%
      criterion for clinically significant change did not achieve a reliable level of
      improvement (95% confidence interval). CONCLUSIONS & INFERENCES: Children's self
      reported ratings of being better may not be statistically reliable. A combined
      approach in which children must report improvement as better and achieve a
      statistically significant change may be more appropriate for outcomes in clinical
      trials.

PMID- 25845926
TI  - Substrate Specificity Profiling of Peptidyl-Lys Metallopeptidase of Armillaria
      mellea by FRET Based Peptide Library.
AB  - Determining the substrate specificity of a protease is essential for developing
      assays, inhibitors and understanding the mechanisms of the enzyme. In this work,
      we have profiled the specificity of Peptidyl-Lys metallopeptidase, (LysN), of
      Armillaria mellea, by a synthetic fluorescence resonance energy transfer (FRET)
      positional-scanning library. The library was based on a reference sequence K(Abz)
      S-A-Q-K-M-V-S-K(Dnp), where the fluorescent donor is 2-aminobenzamide and the
      quencher is N-2,4-dinitrophenyl. Each position was varied between 19 different
      amino acids one by one, to reveal the specificity of the protease. LysN exhibits
      strict specificity for lysine in S1', and has less specificity moving further
      away from the scissile bond. Additivity between the subsites was observed and the
      best substrate identified was K(Abz)-M-R-F-K-R-R-R-K(Dnp) with a kcat/KM of 42.6
      uM/s. Based on a homology structure model the reference substrate was fitted into
      the active site using molecular dynamics to propose peptide-enzyme interactions. 

PMID- 25845927
TI  - Non-carbapenem therapy of urinary tract infections caused by extended-spectrum
      beta-lactamase-producing Enterobacteriaceae.
AB  - PURPOSE: We determined the prevalence of ESBL Enterobacteriaceae in urinary tract
      infections among inpatients, identified risk factors of acquisition, and
      evaluated the effectiveness of alternatives to carbapenems. METHODS: The
      clinical, microbiological, and therapeutic data as well as the outcomes were
      recorded for all ESBL-E positive urine samples for three months. RESULTS: Thirty
      one (4%) of the 762 Enterobacteriaceae positive cultures were ESBL producers. The
      predisposing conditions for being infected with those strains were:
      immunodepression (61%), recent hospitalization (52%), recent antibiotic therapy
      (52%), and urinary catheterization (61%). 19% of infections were community
      acquired. The seven cases of acute pyelonephritis and five of prostatitis were
      treated with piperacillin-tazobactam (5), fluoroquinolones (4), ceftazidime (2),
      or carbapenems (only 1) after specialized advice. Four (33%) patients relapsed at
      week 10: three were immunodepressed and three presented with bacteremia.
      CONCLUSIONS: Alternatives to carbapenems (especially piperacillin-tazobactam)
      seem to be a good option for non-bacteremic UTI in immunocompetent patients.

PMID- 25845928
TI  - The current role of next-generation DNA sequencing in routine care of patients
      with hereditary cardiovascular conditions: a viewpoint paper of the European
      Society of Cardiology working group on myocardial and pericardial diseases and
      members of the European Society of Human Genetics.

PMID- 25845929
TI  - Neutrophil extracellular traps: a new source of tissue factor in
      atherothrombosis.

PMID- 25845930
TI  - Patient outcomes according to adherence to treatment guidelines for rhythm
      control of atrial fibrillation.
AB  - BACKGROUND: Although guidelines for antiarrhythmic drug therapy in atrial
      fibrillation (AF) were published in 2006, it remains uncertain whether adherence
      to these guidelines affects patient outcomes. METHODS AND RESULTS: We
      retrospectively evaluated the records of 5976 consecutive AF patients who were
      prescribed at least 1 antiarrhythmic drug between 2006 and 2013. Patients with 1
      or more prescribed antiarrhythmic drugs that did not comply with guideline
      recommendations comprised the non-guideline-directed group (=2920); the remainder
      constituted the guideline-directed group (=3056). Time to events was assessed
      using the survival analysis method and adjusted for covariates using Cox
      regression. Rates of adherence to the guidelines increased significantly with a
      higher degree of prescriber specialization in arrhythmias (49%, 55%, and 60% for
      primary care physicians, general cardiologists, and cardiac electrophysiologists,
      respectively, P=0.001) for the first prescribed antiarrhythmic drug. Compared to
      the non-guideline-directed group, the guideline-directed group had higher rates
      of heart failure, but lower baseline CHADS2-VASc scores (P<0.001) and lower rates
      of coronary artery disease, valvular disease, hypertension, hyperlipidemia,
      pulmonary disease, and renal insufficiency (P<0.05 for all). During 45 +/- 26
      months follow-up, the guideline-directed group had a lower risk of AF recurrence
      (hazard ratio=0.86, 95% CI=0.80 to 0.93), fewer hospital admissions for AF
      (hazard ratio=0.87, 95% CI=0.79 to 0.97), and fewer procedures for recurrent AF,
      including electrical cardioversion, pacemaker implantation, and atrioventricular
      nodal ablation (P<0.01 for all). The mortality and stroke risks were similar
      between the groups. CONCLUSIONS: Adherence to published guidelines in the
      antiarrhythmic management of AF is associated with improved patient outcomes.

PMID- 25845932
TI  - Current lipid-modifying agents.

PMID- 25845931
TI  - Endogenously generated omega-3 fatty acids attenuate vascular inflammation and
      neointimal hyperplasia by interaction with free fatty acid receptor 4 in mice.
AB  - BACKGROUND: Omega-3 polyunsaturated fatty acids (omega3 PUFAs) suppress
      inflammation through activation of free fatty acid receptor 4 (FFAR4), but this
      pathway has not been explored in the context of cardiovascular disease. We aimed
      to elucidate the involvement of FFAR4 activation by omega3 PUFAs in the process
      of vascular inflammation and neointimal hyperplasia in mice. METHODS AND RESULTS:
      We used mice with disruption of FFAR4 (Ffar4(-/-)), along with a strain that
      synthesizes high levels of omega3 PUFAs (fat-1) and a group of crossed mice
      (Ffar4(-/-)/fat-1), to elucidate the role of FFAR4 in vascular dysfunction using
      acute and chronic thrombosis/vascular remodeling models. The presence of FFAR4 in
      vascular-associated cells including perivascular adipocytes and macrophages, but
      not platelets, was demonstrated. omega3 PUFAs endogenously generated in fat-1
      mice (n=9), but not in compound Ffar4(-/-)/fat-1 mice (n=9), attenuated femoral
      arterial thrombosis induced by FeCl3. Neointimal hyperplasia and vascular
      inflammation in the common carotid artery were significantly curtailed 4 weeks
      after FeCl3 injury in fat-1 mice (n=6). This included greater luminal diameter
      and enhanced blood flow, reduced intima:media ratio, and diminished macrophage
      infiltration in the vasculature and perivascular adipose tissue compared with
      control mice. These effects were attenuated in the Ffar4(-/-)/fat-1 mice.
      CONCLUSIONS: These results indicate that omega3 PUFAs mitigate vascular
      inflammation, arterial thrombus formation, and neointimal hyperplasia by
      interaction with FFAR4 in mice. Moreover, the omega3 PUFA-FFAR4 pathway decreases
      inflammatory responses with dampened macrophage transmigration and infiltration.

PMID- 25845933
TI  - Synthesis of trans-16-triazolyl-13alpha-methyl-17-estradiol diastereomers and the
      effects of structural modifications on their in vitro antiproliferative
      activities.
AB  - Novel 16-triazoles in the 13alpha-estrone series were synthesized via Cu(I)
      catalyzed azide-alkyne cycloaddition of the two diastereomeric (on C-16 and on C
      17) 16-azido-13alpha-estra-1,3,5(10)-trien-17-ol 3-benzyl ethers with substituted
      phenylacetylenes. The new heterocyclic derivatives were evaluated in vitro by
      means of MTT assays for antiproliferative activity against a panel of human
      adherent cancer cell lines (HeLa, MCF-7, A431, A2780, T47D, MDA-MB-231 and MDA-MB
      361). The inversion of the configurations at C-16 and C-17 selectively affected
      the growth-inhibitory properties of the tested compounds. The 16beta,17alpha
      isomers generally proved to be potent on all cell lines, with IC50 values
      comparable to those of the reference agent cisplatin. Change of the substitution
      pattern of the phenyl group of the acetylene led to great differences in
      antiproliferative properties. Exclusively the p-phenyl-substituted triazoles
      exerted high cytostatic effects. One of the most potent compounds activated
      caspase-3 and caspase-9 without influencing caspase-8, confirming the induction
      of apoptosis via the intrinsic pathway. 

PMID- 25845934
TI  - A review of 1alpha,25(OH)2D3 dependent Pdia3 receptor complex components in Wnt5a
      non-canonical pathway signaling.
AB  - Wnt5a and 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3] regulate endochondral
      ossification. 1alpha,25(OH)2D3 initiates its calcium-dependent effects via its
      membrane-associated receptor, protein disulfide isomerase A3 (Pdia3).
      1alpha,25(OH)2D3 binding to Pdia3 triggers the interaction between Pdia3 and
      phospholipase A2 (PLA2)-activating protein (PLAA), resulting in downstream
      activation of calcium/calmodulin-dependent protein kinase II (CaMKII), PLA2, and
      protein kinase C (PKC). Wnt5a initiates its calcium-dependent effects via binding
      its receptors Frizzled2 (FZD2) and Frizzled5 (FZD5) and receptor tyrosine kinase
      like orphan receptor 2 (ROR2), activating intracellular calcium release and
      stimulating PKC and CaMKII. Recent efforts to determine the inter-relation
      between Wnt5a and 1alpha,25(OH)2D3 signaling pathways have demonstrated that
      Wnt5a signals through a CaMKII/PLA2/PGE2/PKC cascade in chondrocytes and
      osteoblasts in which the components of the Pdia3 receptor complex were required.
      Furthermore, ROR2, but not FZD2 or FZD5, was required to mediate the calcium
      dependent actions of 1alpha,25(OH)2D3. This review provides evidence that
      1alpha,25(OH)2D3 and Wnt5a mediate their calcium-dependent pathways via similar
      receptor components and proposes that these pathways may interact since they are
      competing for the same receptor complex components. 

PMID- 25845935
TI  - Heat waves imposed during early pod development in soybean (Glycine max) cause
      significant yield loss despite a rapid recovery from oxidative stress.
AB  - Heat waves already have a large impact on crops and are predicted to become more
      intense and more frequent in the future. In this study, heat waves were imposed
      on soybean using infrared heating technology in a fully open-air field
      experiment. Five separate heat waves were applied to field-grown soybean (Glycine
      max) in central Illinois, three in 2010 and two in 2011. Thirty years of
      historical weather data from Illinois were analyzed to determine the length and
      intensity of a regionally realistic heat wave resulting in experimental heat wave
      treatments during which day and night canopy temperatures were elevated 6 
      degrees C above ambient for 3 days. Heat waves were applied during early or late
      reproductive stages to determine whether and when heat waves had an impact on
      carbon metabolism and seed yield. By the third day of each heat wave, net
      photosynthesis (A), specific leaf weight (SLW), and leaf total nonstructural
      carbohydrate concentration (TNC) were decreased, while leaf oxidative stress was
      increased. However, A, SLW, TNC, and measures of oxidative stress were no
      different than the control ca. 12 h after the heat waves ended, indicating rapid
      physiological recovery from the high-temperature stress. That end of season seed
      yield was reduced (~10%) only when heat waves were applied during early pod
      developmental stages indicates the yield loss had more to do with direct impacts
      of the heat waves on reproductive process than on photosynthesis. Soybean was
      unable to mitigate yield loss after heat waves given during late reproductive
      stages. This study shows that short high-temperature stress events that reduce
      photosynthesis and increase oxidative stress resulted in significant losses to
      soybean production in the Midwest, U.S. The study also suggests that to mitigate
      heat wave-induced yield loss, soybean needs improved reproductive and
      photosynthetic tolerance to high but increasingly common temperatures.

PMID- 25845937
TI  - Protein-losing enteropathy cured by resection of adenomatous goiter: report of a
      case.
AB  - A 51-year-old Japanese woman presented to our hospital with systemic edema and
      general fatigue. Her serum albumin level was very low (1.5 g/dL). Technetium-99 m
      human serum albumin ((99m)Tc-HSA) scintigraphy showed albumin leakage from the
      upper small bowel. Magnetic resonance lymphangiography showed dilated lymphatic
      vessels in the chest, whereas double-balloon enteroscopy (DBE) showed white villi
      and chyle leakage in the deeper part of the duodenal mucosa. A duodenal mucosa
      biopsy specimen revealed lymphangiectasia. She was diagnosed with protein-losing
      enteropathy (PLE). Treatment with a fat-restricted diet and tranexamic acid-
      previously reported to be effective against PLE--was attempted, but was
      ineffective. A thyroid tumor was simultaneously detected in her left neck, and
      was found to extend to the mediastinum on computed tomography. The tumor (size,
      >5 cm) was resected, and a pathological diagnosis of adenomatous goiter was made.
      The patient's serum albumin level increased to normal levels within 1 month
      postoperatively. After 6 months, (99m)Tc-HSA scintigraphy showed no albumin
      leakage from the gastrointestinal tract, and disappearance of white villi and
      chyle leakage on DBE. No lymphangiectasia was noted in the biopsy specimen.
      Adenomatous goiter was thus considered the cause of the PLE, possibly through
      lymph flow obstruction in the mediastinum.

PMID- 25845936
TI  - Neuronally produced versican V2 renders C-fiber nociceptors IB4 -positive.
AB  - A subpopulation of nociceptors, the glial cell line-derived neurotrophic factor
      (GDNF)-dependent, non-peptidergic C-fibers, expresses a cell-surface
      glycoconjugate that can be selectively labeled with isolectin B4 (IB4 ), a
      homotetrameric plant lectin from Griffonia simplicifolia. We show that versican
      is an IB4 -binding molecule in rat dorsal root ganglion neurons. Using reverse
      transcriptase polymerase chain reaction (RT-PCR), in situ hybridization and
      immunofluorescence experiments on rat lumbar dorsal root ganglion, we provide the
      first demonstration that versican is produced by neurons. In addition, by probing
      Western blots with splice variant-specific antibodies we show that the IB4 
      binding versican contains only the glycosaminoglycan alpha domain. Our data
      support V2 as the versican isoform that renders this subpopulation of nociceptors
      IB4 -positive (+). A subset of nociceptors, the GDNF-dependent non-peptidergic C
      fibers can be characterized by its reactivity for isolectin B4 (IB4), a plant
      lectin from Griffonia simplicifolia. We have previously demonstrated that
      versican V2 binds IB4 in a Ca2 + -dependent manner. However, given that versican
      is thought to be the product of glial cells, it was questionable whether versican
      V2 can be accountable for the IB4-reactivity of this subset of nociceptors. The
      results presented here prove - for the first time - a neuronal origin of versican
      and suggest that versican V2 is the molecule that renders GDNF-dependent non
      peptidergic C-fibers IB4-positive. 

PMID- 25845938
TI  - Stereocontrolled synthesis of vicinally functionalized piperidines by
      nucleophilic beta-addition of alkyllithiums to alpha-aryl substituted piperidine
      enecarbamates.
AB  - Substituted piperidines are emerging as important medicinally-active structural
      motifs. Here, we report highly stereoselective carbolithiation reactions of alpha
      aryl piperidine enecarbamates that offer direct access to vicinally-substituted
      piperidine compounds. We have also demonstrated that the carbanion intermediates
      can be trapped with a carbon electrophile. 

PMID- 25845939
TI  - Prenatal Detection of Coarctation of the Aorta in a Non-selected Population: A
      Prospective Analysis of 10 Years of Experience.
AB  - The objective of this study was to assess the ability of different parameters to
      identify fetuses requiring neonatal care for coarctation of the aorta (CoA).
      Between January 2003 and December 2012, 175 fetuses referred for great vessel
      disproportion were divided into two groups: group A (n = 51) with high risk of
      CoA and delivery planned in tertiary care referral center and group B (n = 124)
      with no increased risk of CoA. In group A, diagnosis of CoA was confirmed in
      38/51 (74 %). In group B, 2/124 had CoA. Multiple logistic regression analysis
      identified the best combination as diffusely hypoplastic and/or angular aortic
      arches, ventricular septal defect and aortic valve diameter <5 mm at 36-week
      gestational age (GA). Positive predictive value was 75 % when vessel
      disproportion was noted before 28-week GA and 73 % in the third trimester.
      Postnatal diagnosis involved 38 cases of CoA which had not been referred. One
      case of CoA diagnosed after birth was referred prenatally for difficulty of
      screening without any defect. The results of our prospective study are in
      agreement with those of previous series, but our false positive rate was lower
      especially when the diagnosis of vascular disproportion was made at third
      trimester. The performance of fetal cardiac screening does not seem to be very
      good, but prenatal diagnosis is probably not always possible: Among our three
      false negative cases, two had isolated vascular disproportion and the third no
      risk factors. 

PMID- 25845940
TI  - Dual-Chamber Stimulation with Single-Lead VDD Pacing System in Mustard Surgery.
AB  - Sinus node disease is a problem encountered in patients after the Mustard
      surgery, requiring a pacemaker implantation. The knowledge of the complexity
      anatomy is crucial because of the possible challenges associated with this
      procedure. We report a case of a 24-year-old woman presented with symptomatic
      bradycardia, in which a bicameral stimulation using a single-lead VDD pacing
      system was successfully performed. 

PMID- 25845941
TI  - In-line Filtration Decreases Systemic Inflammatory Response Syndrome, Renal and
      Hematologic Dysfunction in Pediatric Cardiac Intensive Care Patients.
AB  - Cardiac surgery with cardiopulmonary bypass (CPB) frequently leads to systemic
      inflammatory response syndrome (SIRS) with concomitant organ malfunction. Infused
      particles may exacerbate inflammatory syndromes since they activate the
      coagulation cascade and alter inflammatory response or microvascular perfusion.
      In a randomized, controlled, prospective trial, we have previously shown that
      particle-retentive in-line filtration prevented major complications in critically
      ill children. Now, we investigated the effect of in-line filtration on major
      complications in the subgroup of cardiac patients. Children admitted to tertiary
      pediatric intensive care unit were randomized to either control or filter group
      obtaining in-line filtration throughout complete infusion therapy. Risk
      differences and 95 % confidence intervals (CI) of several complications such as
      SIRS, sepsis, mortality, various organ failure and dysfunction were compared
      between both groups using the Wald method. 305 children (n = 150 control, n = 155
      filter group) with cardiac diseases were finally analyzed. The majority was
      admitted after cardiac surgery with CPB. Risk of SIRS (-11.3 %; 95 % CI -21.8 to 
      0.5 %), renal (-10.0 %; 95 % CI -17.0 to -3.0 %) and hematologic (-8.1 %; 95 % CI
      -14.2 to -0.2 %) dysfunction were significantly decreased within the filter
      group. No risk differences were demonstrated for occurrence of sepsis, any other
      organ failure or dysfunctions between both groups. Infused particles might
      aggravate a systemic hypercoagulability and inflammation with subsequent organ
      malfunction in pediatric cardiac intensive care patients. Particle-retentive in
      line filtration might be effective in preventing SIRS and maintaining renal and
      hematologic function. In-line filtration offers a novel therapeutic option to
      decrease morbidity in cardiac intensive care. 

PMID- 25845942
TI  - Phenotype of Children with QT Prolongation Identified Using an Institution-Wide
      QT Alert System.
AB  - QT prolongation is an independent risk factor for cardiovascular mortality in
      adults. However, there is little information available on pediatric patients with
      QT prolongation and their outcomes. Herein, we evaluated the prevalence of QT
      prolongation in pediatric patients identified by an institution-wide QT alert
      system, and the spectrum of their phenotype. Patients with documented QT
      prolongation on an ECG obtained between November 2010 and June 2011 were
      included. There were 1303 pediatric ECGs, and 68 children had electrographically
      isolated QT prolongation. Comprehensive review of medical records was performed
      with particular attention to QT-prolonging clinical, laboratory, and medication
      data, which were summarized into a pro-QTc score. Overall, 68 (5 %) pediatric
      patients had isolated QT prolongation. The mean age of this pediatric cohort was
      9 +/- 6 years, and the average QTc was 494 +/- 42 ms. All children had 1 or more
      QT-prolonging risk factor(s), most commonly QT-prolonging medications. One
      patient was identified with congenital long QT syndrome (LQTS), which was not
      previously diagnosed. In one-year follow-up, only one pediatric death (non
      cardiac) occurred (1.5 %). Potentially QT-offending/pro-arrhythmic medications
      were changed in 80 % of pediatric patients after the physician received the QT
      alert. Children with QT prolongation had very low mortality and minimal
      polypharmacy. Still, medications and other modifiable conditions were the most
      common causes of QT prolongation. Children with a prolonged QTc should be
      evaluated for modifiable QT-prolonging factors. However, if no risk factors are
      present or the QTc does not attenuate after risk factor modification/removal, the
      child should be evaluated for congenital LQTS.

PMID- 25845943
TI  - InSAC: A novel sub-nuclear body essential for Interleukin-6 and -10 RNA
      processing and stability.
AB  - Dysregulation of cytokine expression causes inflammatory diseases or chronic
      infection conditions. We have identified that Tat-activating regulatory DNA
      binding protein-43 (TDP-43) is involved in cytokine RNA processing in order to
      promote an optimal immune response. The interaction of TDP-43 with spliceosomal
      components from the Cajal body leads to the formation of a novel sub-nuclear body
      called the Interleukin (IL)-6 and IL-10 Splicing Activating Compartment (InSAC).
      TDP-43 binds to the IL-6 and IL-10 RNAs in a sequence-dependent manner. In cell
      based studies, we observed that lipopolysaccharide (LPS) stimulation induces the
      formation of the InSAC through TDP-43 ubiquitination, thereby influencing the
      processing and expression levels of IL-6 RNA. Moreover, TDP-43 knockdown in vivo
      results in a decrease in IL-6 production and its RNA splicing and stability.
      Thus, these findings demonstrate that the InSAC is linked to the activation and
      modulation of the immune response.

PMID- 25845944
TI  - Broadly neutralizing antibodies against the rapidly evolving porcine reproductive
      and respiratory syndrome virus.
AB  - Neutralizing antibodies are a critical part of the immune armory for defense
      against viruses, and the mechanism by which many effective vaccines work to
      protect against viral infections. However, infections by rapidly evolving and
      genetically diverse viruses are often characterized by ineffective neutralizing
      antibody responses. Porcine reproductive and respiratory syndrome virus (PRRSV)
      is a highly genetically diverse RNA virus that causes PRRS, the most significant
      disease of pigs worldwide. The prevailing view of immunity to PRRSV is
      characterized by delayed and ineffectual production of neutralizing antibodies
      lacking cross-reactivity that is necessary for vaccine efficacy. Using an ELISA
      based neutralizing assay developed to analyze PRRSV growth in porcine alveolar
      macrophages, the naturally permissive cell of PRRSV, we showed that sera from
      previously infected commercial sows had high levels of neutralizing activity
      against diverse PRRSV strains, including across distinct genotypes of PRRSV.
      Fifty percent cross-neutralization titers in excess of 1/1024 were observed.
      Neutralizing activity was dose-dependent and was maintained in the immunoglobulin
      fraction. Presence of high-titer, anti-PRRSV antibody activity that cross
      neutralizes diverse strains of virus has prompted reevaluation of the role of
      neutralizing antibodies for cross-protection against PRRSV under field
      conditions. Understanding conditions that favor development of cross-neutralizing
      activity will be crucial for improved strategies to enhance cross-protection
      against PRRSV. More detailed studies are expected to elucidate mechanisms of
      neutralizing antibody production and maturation and to investigate conserved
      epitope targets of cross-neutralization in this rapidly evolving virus. 

PMID- 25845945
TI  - Development of an aerobic capacity prediction model from one-mile run/walk
      performance in adolescents aged 13-16 years.
AB  - A popular algorithm to predict VO2Peak from the one-mile run/walk test (1MRW)
      includes body mass index (BMI), which manifests practical issues in school
      settings. The purpose of this study was to develop an aerobic capacity model from
      1MRW in adolescents independent of BMI. Cardiorespiratory endurance data were
      collected on 90 adolescents aged 13-16 years. The 1MRW was administered on an
      outside track and a laboratory VO2Peak test was conducted using a maximal
      treadmill protocol. Multiple linear regression was employed to develop the
      prediction model. Results yielded the following algorithm: VO2Peak = 7.34 * (1MRW
      speed in m s(-1)) + 0.23 * (age * sex) + 17.75. The New Model displayed a
      multiple correlation and prediction error of R = 0.81, standard error of the
      estimate = 4.78 ml kg(-1) . min(-1), with measured VO2Peak and good criterion
      referenced (CR) agreement into FITNESSGRAM's Healthy Fitness Zone (Kappa = 0.62;
      percentage agreement = 84.4%; Phi = 0.62). The New Model was validated using k
      fold cross-validation and showed homoscedastic residuals across the range of
      predicted scores. The omission of BMI did not compromise accuracy of the model.
      In conclusion, the New Model displayed good predictive accuracy and good CR
      agreement with measured VO2Peak in adolescents aged 13-16 years.

PMID- 25845946
TI  - Immunopathogenesis of Myocarditis: The Interplay Between Cardiac Fibroblast
      Cells, Dendritic Cells, Macrophages and CD4+ T Cells.
AB  - The myocardium responds to aetiologically different pathological injuries through
      a common multistep process involving highly co-ordinated interactions between
      cardiac and immune cells. Cardiac fibroblast cells which constitute the prevalent
      cell type in the heart to have their functional effects that express contractile
      proteins and exhibit increased migratory, proliferative and secretory properties.
      During the pathogenesis of myocarditis, cardiac fibroblast, dendritic cells,
      macrophages, CD4(+) T cells and other immune cells are known to play variable
      roles. It is becoming increasingly clear that cardiac fibroblasts are not passive
      players in immune responses, and several evidences show this through the release
      of soluble signals and/or direct interactions with these immune cells. Typically,
      fibroblasts are involved in synthesizing factors such as cytokines, chemokines,
      prostanoids, matrix components and matrix-degrading enzymes to influence
      dendritic cells, CD4(+) T cells and macrophage functions and vice versa in the
      pathogenesis of myocarditis. Again, evidence proves a crosstalk between cardiac
      fibroblasts and immune cells recruited into the myocardium during myocarditis in
      the microenvironments. This piece reviews the properties and roles of cardiac
      fibroblast cells, dendritic cells, macrophages and CD4(+) T cells in the
      pathogenesis of myocarditis, and how these cells interplay on each other in the
      microenvironment. 

PMID- 25845947
TI  - Are There Modifiable Risk Factors for Hospital Readmission After Total Hip
      Arthroplasty in a US Healthcare System?
AB  - BACKGROUND: Although total hip arthroplasty (THA) is a successful procedure, 4%
      to 11% of patients who undergo THA are readmitted to the hospital. Prior studies
      have reported rates and risk factors of THA readmission but have been limited to
      single-center samples, administrative claims data, or Medicare patients. As a
      result, hospital readmission risk factors for a large proportion of patients
      undergoing THA are not fully understood. QUESTIONS/PURPOSES: (1) What is the
      incidence of hospital readmissions after primary THA and the reasons for
      readmission? (2) What are the risk factors for hospital readmissions in a large,
      integrated healthcare system using current perioperative care protocols? METHODS:
      The Kaiser Permanente (KP) Total Joint Replacement Registry (TJRR) was used to
      identify all patients with primary unilateral THAs registered between January 1,
      2009, and December 31, 2011. The KPTJRR's voluntary participation is 95%. A
      logistic regression model was used to study the relationship of risk factors
      (including patient, clinical, and system-related) and the likelihood of 30-day
      readmission. Readmissions were identified using electronic health and claims
      records to capture readmissions within and outside the system. Odds ratio (OR)
      and 95% confidence intervals (CIs) were calculated. Of the 12,030 patients
      undergoing primary THAs included in the study, 59% (n = 7093) were women and
      average patient age was 66.5 years (+/- 10.7). RESULTS: There were 436 (3.6%)
      patients with hospital readmissions within 30 days of the index procedure. The
      most common reasons for readmission were infection and inflammatory reaction
      resulting from internal joint prosthetic (International Classification of
      Diseases, 9(th) Revision, Clinical Modification [ICD-9-CM] 996.66, 7.0%); other
      postoperative infection (ICD-9-CM 998:59, 5.5%); unspecified septicemia (ICD-9-CM
      038.9, 4.9%); and dislocation of a prosthetic joint (ICD-9-CM 996.42, 4.7%). In
      adjusted models, the following factors were associated with an increased
      likelihood of 30-day readmission: medical complications (OR, 2.80; 95% CI, 1.59
      4.93); discharge to facilities other than home (OR, 1.89; 95% CI, 1.39-2.58);
      length of stay of 5 or more days (OR, 1.80; 95% CI, 1.22-2.65) versus 3 days;
      morbid obesity (OR, 1.74; 95% CI, 1.25-2.43); surgeries performed by high-volume
      surgeons compared with medium volume (OR, 1.53; 95% CI, 1.14-2.08); procedures at
      lower-volume (OR, 1.41; 95% CI, 1.07-1.85) and medium-volume hospitals (OR, 1.81;
      95% CI, 1.20-2.72) compared with high-volume ones; sex (men: OR, 1.51; 95% CI,
      1.18-1.92); obesity (OR, 1.32; 95% CI, 1.02-1.72); race (black: OR, 1.26; 95% CI,
      1.02-1.57); increasing age (OR, 1.03; 95% CI, 1.01-1.04); and certain
      comorbidities (pulmonary circulation disease, chronic pulmonary disease,
      hypothyroidism, and psychoses). CONCLUSIONS: The 30-day hospital readmission rate
      after primary THA was 3.6%. Modifiable factors, including obesity, comorbidities,
      medical complications, and system-related factors (hospital), have the potential
      to be addressed by improving the health of patients before this elective
      procedure, patient and family education and planning, and with the development of
      high-volume centers of excellence. Nonmodifiable factors such as age, sex, and
      race can be used to establish patient and family expectations regarding risk of
      readmission after THA. Contrary to other studies and the finding of increased
      hospital volume associated with lower risk of readmission, higher volume surgeons
      had a higher risk of patient readmission, which may be attributable to the
      referral patterns in our organization. LEVEL OF EVIDENCE: Level III, therapeutic
      study.

PMID- 25845948
TI  - Morbid Obesity: Increased Risk of Failure After Aseptic Revision TKA.
AB  - BACKGROUND: Patients with obesity are known to have a higher risk of
      complications after primary TKA; however, there is a paucity of data regarding
      the effects of obesity with revision TKAs. QUESTIONS/PURPOSES: We asked the
      following questions : (1) Are patients with morbid obesity (BMI>=40 kg/m2) at
      greater risk for repeat revision, reoperation, or periprosthetic joint infection
      (PJI) compared with patients without obesity (BMI<30 kg/m2) after an index
      revision TKA performed for aseptic reasons? (2) Do patients who are not obese
      achieve higher Knee Society pain and function scores after revision TKA for
      aseptic reasons? METHODS: We used a retrospective cohort study with 1:1 matching
      for sex, age (+/-3 years) and date of surgery (+/-1 year) to compare patients
      with morbid obesity with patients without obesity with respect to repeat
      revision, reoperation, and PJI. Using our institution's total joint registry, we
      identified 1291 index both-component (femoral and tibial) aseptic revision TKAs
      performed during a 15-year period (1992-2007). Of these, 120 revisions were in
      patients with morbid obesity (BMI>=40 kg/m2) and 624 were in patients with a BMI
      less than 30 kg/m2. We then considered only patients with a minimum 5-year
      followup, which was available for 77% of patients with morbid obesity and 76% of
      patients with a BMI less than 30 kg/m2 (p=0.84). All patients with morbid obesity
      who met criteria were included (morbid obesity group: n=93; average followup, 7.9
      years) and compared with a matched cohort of patients with a BMI less than 30
      kg/m2 (nonmorbid obesity group: n=93; average followup, 7.3 years). Medical
      records were reviewed to gather details regarding complications and clinical
      outcomes. RESULTS: Overall, patients with morbid obesity had an increased risk of
      repeat revision (hazard ratio [HR], 3.8; 95% CI, 1.2-16.5; p<0.02), reoperation
      (HR, 2.9; 95% CI, 1.3-7.4; p<0.02), and PJI (HR, 6.4; 95% CI, 1.2-119.7; p<0.03).
      Implant survival rates were 96% (95% CI, 92%-100%) and 100% at 5 years, and 81%
      (95% CI, 70%-92%) and 93% (95% CI, 86%-100%) at 10 years for the patients with
      morbid obesity and those without morbid obesity, respectively (p=0.02). At 10
      years, The Knee Society pain (90 [95% CI, 88-92] vs 76 [95% CI, 71-81]; p<0.01)
      and function (61 [95% CI, 53-69] vs 57 [95% CI, 42-52]; p<0.01) scores were
      higher in patients with a BMI less than 30 kg/m2 compared with patients with
      morbid obesity. CONCLUSION: Morbid obesity is associated with increased rates of
      rerevision, reoperation, and PJI after aseptic revision TKA. As the time
      sensitive nature of revision surgery may not always allow for patient or
      comorbidity optimization, these results emphasize the need for improving our care
      of patients with morbid obesity earlier on during the osteoarthritic process.
      Additional studies are needed to risk stratify patients in the morbidly obese
      population to better guide patient selection and effective optimization. LEVEL OF
      EVIDENCE: Level III, therapeutic study.

PMID- 25845950
TI  - Art in science: the stage of the human body--the anatomical theatre of Bologna.

PMID- 25845949
TI  - Does Combined Intra- and Extraarticular ACL Reconstruction Improve Function and
      Stability? A Meta-analysis.
AB  - BACKGROUND: ACL reconstruction aims to restore knee function and stability;
      however, rotational stability may not be completely restored by use of standard
      intraarticular reconstruction alone. Although individual studies have not shown
      the superiority of combined ACL reconstruction compared with isolated
      intraarticular reconstruction in terms of function and stability, biomechanical
      principles suggest a combined approach may be helpful, therefore pooling (meta
      analyzing) the available randomized clinical studies may be enlightening.
      QUESTIONS/PURPOSES: We performed a meta-analysis to determine whether combining
      extraarticular with intraarticular ACL reconstruction would lead to: (1) similar
      knee function measured by the IKDC evaluation, return-to-activity, and Tegner
      Lysholm scores, compared with isolated intraarticular reconstruction; (2)
      increased stability measured by pivot shift and instrumented Lachman examination;
      and (3) any differences in complications and adverse events? METHODS: To identify
      randomized controlled trials (RCTs) comparing combined intra- and extrarticular
      ACL reconstruction (combined reconstruction) with intraarticular ACL
      reconstruction only, we searched MEDLINE, EMBASE, SPORTDiscus, Latin American and
      Caribbean Health Sciences (LILACS), and the Cochrane Central Register of
      Controlled Trials, and followed the Preferred Reporting Items for Systematic
      Reviews and Meta-Analyses (PRISMA) criteria. The main outcomes we sought were
      patient function and stability and complications after ACL reconstruction. Of 386
      identified studies, eight RCTs were included (n=682 participants; followup, 12-84
      months; men to women ratio, 2.17:1) in our meta-analysis. Study quality (internal
      validity) was assessed using the Cochrane risk-of-bias tool; in general, we found
      a moderate quality of evidence of the included studies. RESULTS: When functional
      outcomes were compared, we found no difference between patients who underwent
      intraarticular ACL reconstruction only and those who underwent combined
      reconstruction (IKDC, return-to-activity, and Tegner Lysholm scores). However,
      patients who underwent combined reconstruction were more likely to show improved
      stability based on the pivot shift test (risk ratio [RR], 0.95; 95% CI, 0.91
      0.99; p=0.02) and Lachman test (RR, 0.93; 95% CI, 0.88-0.98; p=0.01). In
      addition, our meta-analysis found no difference between the two treatments in
      terms of general complications or adverse events (RR, 1.31; 95% CI, 0.70-2.34;
      p=0.40) and the proportion of patients whose reconstructions failed (RR, 2.88;
      95% CI, 0.73-11.47; p=0.13). CONCLUSION: Combined intra- and extraarticular ACL
      reconstruction provided marginally improved knee stability and comparable failure
      rates but no difference in patient-reported functional outcomes scores.
      Complications and adverse events such as knee stiffness may be underreported and
      technical factors such as graft placement were difficult to evaluate. Future
      studies are needed to determine whether the small differences in additional
      stability warrant the potential morbidity of the additional extraarticular
      procedure and to determine long-term failure rates.

PMID- 25845951
TI  - Not the Last Word: Geriatric Hip Fracture Centers: The Time Has Come.

PMID- 25845952
TI  - 2015 RIV Abstracts.
AB  - This supplement can be found at the following link: http://www.shmabstracts.com. 

PMID- 25845953
TI  - Current Indications for Implantable Cardioverter Defibrillators in Non-Ischemic
      Cardiomyopathies and Channelopathies.
AB  - Current indications for implantable cardioverter defibrillators (ICDs) in
      patients with channelopathies and cardiomyopathies of non-ischemic origin are
      mainly based on non-randomized evidence. In patients with nonischemic dilated
      cardiomyopathy (NIDCM), there is a tendency towards a beneficial effect on total
      mortality of ICD therapy in patients with significant left ventricular (LV)
      dysfunction. Although an important reduction in sudden cardiac death (SCD) seems
      to be clearly demonstrated in these patients, a net beneficial effect on total
      mortality is unclear mostly in cases with good functional status. Risk
      stratification has been changing over the last two decades in patients with
      hypertrophic cardiomyopathy (HCM). Its risk profile has been delineated in
      parallel with the beneficial effect of ICD in high risk patients. Observational
      results based on "appropriate" ICD interventions do support its usefulness both
      in primary and secondary SCD prevention in these patients. Novel risk models
      quantify the rate of sudden cardiac death in these patients on individual basis.
      Less clear risk stratification is available for cases of arrhythmogenic right
      ventricular cardiomyopathy (ARVC) and in other uncommon familiar
      cardiomyopathies. Main features of risk stratification vary among the different
      channelopathies (long QT syndrome -LQTS-, Brugada syndrome, etc) with great
      debate on the management of asymptomatic patients. For most familiar
      cardiomyopathies, ICD therapy is the only accepted strategy in the prevention of
      SCD. So far, genetic testing has a limited role in risk evaluation and management
      of the individual patient. This review aims to summarize these criticisms and to
      refine the current indications of ICD implantation in patients with
      cardiomyopathies and major channelopathies. 

PMID- 25845954
TI  - Insulin resistance is associated with impaired cardiac sympathetic innervation in
      patients with heart failure.
AB  - AIMS: Insulin resistance (IR) represents, at the same time, cause and consequence
      of heart failure (HF) and affects prognosis in HF patients, but
      pathophysiological mechanisms remain unclear. Hyperinsulinemia, which
      characterizes IR, enhances sympathetic drive, and it can be hypothesized that IR
      is associated with impaired cardiac sympathetic innervation in HF. Yet, this
      hypothesis has never been investigated. Aim of the present observational study
      was to assess the relationship between IR and cardiac sympathetic innervation in
      non-diabetic HF patients. METHODS AND RESULTS: One hundred and fifteen patients
      (87% males; 65 +/- 11.3 years) with severe-to-moderate HF (ejection fraction 32.5
      +/- 9.1%) underwent iodine-123 meta-iodobenzylguanidine ((123)I-MIBG) myocardial
      scintigraphy to assess sympathetic innervation and Homeostasis Model Assessment
      Insulin Resistance (HOMA-IR) evaluation to determine the presence of IR. From
      (123)I-MIBG imaging, early and late heart to mediastinum (H/M) ratios and washout
      rate were calculated. Seventy-two (63%) patients showed IR and 43 (37%) were non
      IR. Early [1.68 (IQR 1.53-1.85) vs. 1.79 (IQR 1.66-1.95); P = 0.05] and late H/M
      ratio [1.50 (IQR 1.35-1.69) vs. 1.65 (IQR 1.40-1.85); P = 0.020] were
      significantly reduced in IR compared with non-IR patients. Early and late H/M
      ratio showed significant inverse correlation with fasting insulinemia and HOMA
      IR. CONCLUSION: Cardiac sympathetic innervation is more impaired in patients with
      IR and HF compared with matched non-IR patients. These findings shed light on the
      relationship among IR, HF, and cardiac sympathetic nervous system. Additional
      studies are needed to clarify the pathogenetic relationship between IR and HF.

PMID- 25845955
TI  - Medial rectus muscle elongation, a technique to treat very large-angle esotropia.
AB  - PURPOSE: The purpose was to describe the medial rectus muscle elongation (MRE)
      procedure to treat very large-angle esotropia (ET) with surgery on a lower number
      of muscles. METHODS: Twenty patients with very large-angle ET (more than 70 PD)
      underwent the MRE procedure. In the MRE procedure, the muscle was split
      longitudinally into three parts. The wider central part was sutured with 6/0
      vicryl and disinserted. The distal end of the peripheral parts (still attached to
      the original insertion), 7-9 mm away from the insertion, was sutured to the
      proximal end of the central part. At the end of the procedure, the distance of
      the anastomosis site from the insertion was named as the final elongation. The
      dose-response effect of the final elongation was calculated in bilateral MRE
      cases. The mean of the dose-response effect, obtained in the binocular surgery
      group, was used in the monocular surgery group to calculate the resection effect
      of lateral rectus (LR) muscle. RESULTS: Eleven patients underwent bilateral MRE
      and nine patients underwent unilateral MRE and LR muscle resection. The mean
      preoperative far and near deviation was 94.10 +/- 19.33 PD. The mean
      postoperative deviation was 14.60 +/- 18.07 PD for far and 14.50 +/- 18.23 PD for
      near deviation. In bilateral MRE cases, the mean dose-response effect of the
      elongation was 5.53 +/- 0.67 PD/mm for far and 5.58 +/- 0.69 PD/mm for near
      deviation. The mean LR muscle resection effect was 6.41 +/- 1.99 PD/mm for far
      and 6.28 +/- 1.93 PD/mm for near deviation. CONCLUSION: The MRE procedure seems
      an acceptable method to treat very large-angle ET with surgery on a lower number
      of muscles.

PMID- 25845956
TI  - Feeding performance of king Mackerel, Scomberomorus cavalla.
AB  - Feeding performance is an organism's ability to capture and handle prey. Although
      bite force is a commonly used metric of feeding performance, other factors such
      as bite pressure and strike speed are also likely to affect prey capture.
      Therefore, this study investigated static bite force, dynamic speeds, and
      predator and prey forces resulting from ram strikes, as well as bite pressure of
      the king mackerel, Scomberomorus cavalla, in order to examine their relative
      contributions to overall feeding performance. Theoretical posterior bite force
      ranged from 14.0-318.7 N. Ram speed, recorded with a rod and reel incorporated
      with a line counter and video camera, ranged from 3.3-15.8B L/s. Impact forces on
      the prey ranged from 0.1-1.9 N. Bite pressure, estimated using theoretical bite
      forces at three gape angles and tooth cross-sectional areas, ranged from 1.7-56.9
      MPa. Mass-specific bite force for king mackerel is relatively low in comparison
      with other bony fishes and sharks, with relatively little impact force applied to
      the prey during the strike. This suggests that king mackerel rely on high
      velocity chases and high bite pressure generated via sharp, laterally compressed
      teeth to maximize feeding performance.

PMID- 25845957
TI  - Words of wisdom. Re: Might men diagnosed with metastatic prostate cancer benefit
      from definitive treatment of the primary tumour? A SEER-based study.

PMID- 25845958
TI  - Words of wisdom. Re: Dissecting the association between metabolic syndrome and
      prostate cancer risk: analysis of a large clinical cohort.

PMID- 25845959
TI  - Words of wisdom. Re: Association between metabolic syndrome and severity of lower
      urinary tract symptoms: an observational study in a 4666 European men cohort.

PMID- 25845960
TI  - Words of wisdom. Re: Surgical outcomes in the management of isolated nodal
      recurrences: a multicenter, international retrospective cohort.

PMID- 25845961
TI  - Words of wisdom. Re: MPDL3280A (anti-PD-L1) treatment leads to clinical activity
      in metastatic bladder cancer.

PMID- 25845962
TI  - Words of wisdom. Re: GreenLightTM laser (XPS) photoselective vapo-enucleation
      versus holmium laser enucleation of the prostate for the treatment of symptomatic
      benign prostate hyperplasia: a randomized controlled study.

PMID- 25845964
TI  - Interaction of Blood Pressure and Body Mass Index With Risk of Incident Atrial
      Fibrillation in a Japanese Urban Cohort: The Suita Study.
AB  - BACKGROUND AND PURPOSE: To prevent stroke, strategies for atrial fibrillation
      (AF) prevention and an early detection of AF by electrocardiogram are essential.
      However, only a limited prospective studies have examined the risk factors for
      AF, even in blood pressure (BP) and body mass index (BMI), which are not clear
      among general populations. We investigated the impacts of BP and BMI on the risk
      of incident AF in a general population. METHODS: A total of 6,906 participants
      (30-84 years) in the Suita Study were prospectively followed up for incident AF.
      Participants were diagnosed with AF if AF or atrial flutter was present on an
      electrocardiogram from a routine health examination (every 2 years) or if AF was
      indicated as a present illness from health examinations and/or medical records
      during follow-up. Adjusted Cox proportional hazard ratios (HRs) were calculated.
      RESULTS: During the 12.8-year follow-up, 253 incident AF events occurred.
      Compared with the systolic BP (SBP) < 120 mm Hg and normal-weight, the adjusted
      HRs (95% confidence intervals; CIs) of incident AF in the systolic hypertension
      and the overweight (BMI >= 25kg/m(2)) groups were 1.74 (1.22-2.49) and 1.35 (1.01
      1.80), respectively. Compared with SBP < 120 mm Hg and normal weight, the
      adjusted HRs (95% CIs) of incident AF in the SBP = 120-139 mm Hg with overweight
      and the systolic hypertension with normal or overweight were 1.72 (1.01-2.91),
      1.66 (1.10-2.50), and 2.31 (1.47-3.65), respectively (P for interaction = 0.04).
      CONCLUSIONS: Systolic prehypertension and overweight are associated with incident
      AF in Japanese population. The association between SBP and AF may be evident by
      overweight.

PMID- 25845965
TI  - 7 Tesla MRI in cerebral small vessel disease.
AB  - Cerebral small vessel disease (SVD) is a major cause of stroke and cognitive
      decline. Magnetic resonance imaging (MRI) currently plays a central role in
      diagnosis, and advanced MRI techniques are widely used in research but are
      limited by spatial resolution. Human 7 Tesla (7T) MRI has recently become
      available offering the ability to image at higher spatial resolution. This may
      provide additional insights into both the vascular pathology itself as well as
      parenchymal markers which could only previously be examined post mortem. In this
      review we cover the advantages and limitations of 7T MRI, review studies in SVD
      performed to date, and discuss potential future insights into SVD which 7T MRI
      may provide. 

PMID- 25845967
TI  - Why What Is Counterfactual Really Matters: A Response to Weisberg and Gopnik ().

PMID- 25845966
TI  - High risk of delisting or death in liver transplant candidates following
      infections: Results from the North American Consortium for the Study of End-Stage
      Liver Disease.
AB  - Because Model for End-Stage Liver Disease (MELD) scores at the time of liver
      transplantation (LT) increase nationwide, patients are at an increased risk for
      delisting by becoming too sick or dying while awaiting transplantation. We
      quantified the risk and defined the predictors of delisting or death in patients
      with cirrhosis hospitalized with an infection. North American Consortium for the
      Study of End-Stage Liver Disease (NACSELD) is a 15-center consortium of tertiary
      care hepatology centers that prospectively enroll and collect data on infected
      patients with cirrhosis. Of the 413 patients evaluated, 136 were listed for LT.
      The listed patients' median age was 55.18 years, 58% were male, and 47% were
      hepatitis C virus infected, with a mean MELD score of 2303. At 6-month follow-up,
      42% (57/136) of patients were delisted/died, 35% (47/136) underwent
      transplantation, and 24% (32/136) remained listed for transplant. The frequency
      and types of infection were similar among all 3 groups. MELD scores were highest
      in those who were delisted/died and were lowest in those remaining listed (25.07,
      24.26, 17.59, respectively; P < 0.001). Those who were delisted or died, rather
      than those who underwent transplantation or were awaiting transplantation, had
      the highest proportion of 3 or 4 organ failures at hospitalization versus those
      transplanted or those continuing to await LT (38%, 11%, and 3%, respectively; P =
      0.004). For those who were delisted or died, underwent transplantation, or were
      awaiting transplantation, organ failures were dominated by respiratory (41%, 17%,
      and 3%, respectively; P < 0.001) and circulatory failures (42%, 16%, and 3%,
      respectively; P < 0.001). LT-listed patients with end-stage liver disease and
      infection have a 42% risk of delisting/death within a 6-month period following an
      admission. The number of organ failures was highly predictive of the risk for
      delisting/death. Strategies focusing on prevention of infections and extrahepatic
      organ failure in listed patients with cirrhosis are required.

PMID- 25845968
TI  - Sorafenib enhances the antitumor effects of anti-CTLA-4 antibody in a murine
      cancer model by inhibiting myeloid-derived suppressor cells.
AB  - This antitumor effect of sorafenib is considered to be dependent not only on its
      direct cytotoxicity to cancer cells but also due to the inhibition of myeloid
      derived suppressor cells (MDSCs). Recently, a novel antibody against cytotoxic T
      lymphocyte antigen 4 (CTLA-4), which activates lymphocytes, is currently in
      clinical applications. The aim of the present study was to investigate the
      synergistic antitumor effects of anti-CTLA-4 antibody (Ab) and sorafenib in a
      murine cancer model. RENCA cells were subcutaneously inoculated into mice, which
      were randomly divided into 4 treatment groups: sorafenib plus anti-CTLA-4 Ab,
      sorafenib plus control Ab, vehicle plus anti-CTLA-4 Ab, and vehicle plus control
      Ab. Single therapy using anti-CTLA-4 Ab suppressed tumor growth, but no
      difference was noted when compared with the single therapy group using sorafenib.
      Notably, the greatest decrease in tumor size was noted with sorafenib plus anti
      CTLA-4 Ab (combination therapy), and the highest rate of tumor rejection was
      observed in the combination therapy group. The number of infiltrating CD4- or CD8
      positive lymphocytes was strongly increased in the combination therapy group.
      These in vivo data indicate that sorafenib increased the immunostimulatory effect
      of anti-CTLA-4 Ab even when sorafenib was used at a low dose. An in vitro study
      using MDSCs and CD8(+) T cells showed that the inhibitory effect of MDSCs on
      CD8(+) T cells was significantly abrogated by the combined use of sorafenib and
      anti-CTLA-4 Ab. Sorafenib suppressed the expression of immunosuppressive factors
      in MDSCs. These data indicate that combination therapy of sorafenib and anti-CTLA
      4 Ab may be effective in advanced kidney cancer patients.

PMID- 25845973
TI  - Comparison of phase-constrained parallel MRI approaches: Analogies and
      differences.
AB  - PURPOSE: Phase-constrained parallel MRI approaches have the potential for
      significantly improving the image quality of accelerated MRI scans. The purpose
      of this study was to investigate the properties of two different phase
      constrained parallel MRI formulations, namely the standard phase-constrained
      approach and the virtual conjugate coil (VCC) concept utilizing conjugate k-space
      symmetry. METHODS: Both formulations were combined with image-domain algorithms
      (SENSE) and a mathematical analysis was performed. Furthermore, the VCC concept
      was combined with k-space algorithms (GRAPPA and ESPIRiT) for image
      reconstruction. In vivo experiments were conducted to illustrate analogies and
      differences between the individual methods. Furthermore, a simple method of
      improving the signal-to-noise ratio by modifying the sampling scheme was
      implemented. RESULTS: For SENSE, the VCC concept was mathematically equivalent to
      the standard phase-constrained formulation and therefore yielded identical
      results. In conjunction with k-space algorithms, the VCC concept provided more
      robust results when only a limited amount of calibration data were available.
      Additionally, VCC-GRAPPA reconstructed images provided spatial phase information
      with full resolution. CONCLUSIONS: Although both phase-constrained parallel MRI
      formulations are very similar conceptually, there exist important differences
      between image-domain and k-space domain reconstructions regarding the calibration
      robustness and the availability of high-resolution phase information.

PMID- 25845974
TI  - Phosphorylation of the cell division protein GpsB regulates PrkC kinase activity
      through a negative feedback loop in Bacillus subtilis.
AB  - Although many membrane Ser/Thr-kinases with PASTA motifs have been shown to
      control bacterial cell division and morphogenesis, inactivation of the Ser/Thr
      kinase PrkC does not impact Bacillus subtilis cell division. In this study, we
      show that PrkC localizes at the division septum. In addition, three proteins
      involved in cell division/elongation, GpsB, DivIVA and EzrA are required for
      stimulating PrkC activity in vivo. We show that GpsB interacts with the catalytic
      subunit of PrkC that, in turn, phosphorylates GpsB. These observations are not
      made with DivIVA and EzrA. Consistent with the phosphorylated residue previously
      detected for GpsB in a high-throughput phosphoproteomic analysis of B. subtilis,
      we show that threonine 75 is the single PrkC-mediated phosphorylation site in
      GpsB. Importantly, the substitution of this threonine by a phospho-mimetic
      residue induces a loss of PrkC kinase activity in vivo and a reduced growth under
      high salt conditions as observed for gpsB and prkC null mutants. Conversely,
      substitution of threonine 75 by a phospho-ablative residue does not induce such
      growth and PrkC kinase activity defects. Altogether, these data show that
      proteins of the divisome control PrkC activity and thereby phosphorylation of
      PrkC substrates through a negative feedback loop in B. subtilis. 

PMID- 25845975
TI  - Variable risk of atopic disease due to indoor fungal exposure in NHANES 2005
      2006.
AB  - BACKGROUND: Exposure to damp indoor environments is associated with increased
      risk of eczema, allergy and asthma. The role of dampness-related exposures and
      risk of allergic diseases are yet to be fully explored in the US population.
      OBJECTIVE: We assess whether exposure to fungi, house dust mites and endotoxin
      increases the risk of eczema, allergy and asthma in children and adults
      participating in NHANES 2005-2006. METHODS: A total of 8412 participants (2849
      were children aged between 6 and 17 years) were recruited in the 2005-2006
      survey. We used multiple logistic regression to investigate whether mildew/musty
      odour and increased concentrations of Alternaria alternata allergen, Aspergillus
      fumigatus antigens, house dust mite and endotoxin antigens increase the risk of
      eczema, allergy and asthma. We stratified models by total IgE < 170 and >= 170
      KU/L to assess allergic and non-allergic asthma outcomes. Exposure to multiple
      biological agents and risk of reporting eczema, allergy and asthma were also
      investigated. RESULTS: Reporting of a mildew/musty odour was associated with
      increased risk of childhood asthma (OR 1.60; 95% CI 1.17-2.19), and adult eczema,
      allergy and asthma (OR 1.92; 95% CI 1.39-2.63, OR 1.59 95% CI 1.26-2.02 and OR
      1.61 95% CI 1.00-2.57, respectively). Risk of asthma was associated with total
      IgE >= 170 KU/L in children (OR 1.81; 95% CI 1.01-3.25) and total IgE < 170 KU/L
      in adults (OR 1.91; 95% CI 1.07-3.42). Children and adults exposed to more than
      eight biological agents present in the home were at reduced risk of eczema (OR
      0.17; 95% CI 0.04-0.77) and asthma (OR 0.49; 95% CI 0.25-0.97), respectively.
      CONCLUSION: Exposure to a mildew/musty odour, as a proxy for exposure to fungus,
      was implicated in an increased risk of atopic diseases. Sensitisation may play a
      different role in children and adults, and exposure to multiple allergens may
      reduce the risk of atopic disease.

PMID- 25845976
TI  - Completely organic multilayer thin film with thermoelectric power factor rivaling
      inorganic tellurides.
AB  - Composed exclusively of organic components, polyaniline (PANi), graphene, and
      double-walled nanotubes (DWNTs) are alternately deposited from aqueous solutions
      using a layer-by-layer assembly. The 40 quadlayer thin film (470 nm thick)
      exhibits electrical conductivity of 1.08 * 10(5) S m(-1) and a Seebeck
      coefficient of 130 MUV K(-1) , producing a thermoelectric power factor of 1825
      MUW m(-1) K(-2) . 

PMID- 25845977
TI  - Potential bias due to outcome-related loss to follow-up in cohort studies on
      incidence of drug injection: systematic review and meta-analysis.
AB  - AIMS: A systematic review and meta-analysis were conducted to synthesize results
      from cohort studies on initiation into drug injection among vulnerable
      populations, to quantify heterogeneity in the estimated incidence rates of drug
      injection and to identify potential sources of heterogeneity and bias. METHODS:
      MEDLINE, EMBASE, PsycINFO and LILACS were searched for relevant studies published
      between 1980 and 2012. Investigators independently reviewed studies for
      inclusion, retrieved information on baseline population characteristics and
      follow-up features and assessed study quality. Study-specific incidence rates of
      drug injection were calculated as the number of new injectors divided by the
      person-years at risk. The I(2) statistic was used to quantify heterogeneity in
      incidence rates across studies, and random-effects meta-regression models were
      used to identify determinants of heterogeneity and bias. RESULTS: Nine cohorts
      totalling 1843 participants met the inclusion criteria, with individual sample
      sizes of 70-415 participants and follow-up lengths of 6 months-3.4 years. The
      incidence of drug injection varied widely, from 2.1 to 24.2 cases per 100 person
      years. The strong between-study heterogeneity (I(2)  = 90%, P<0.001) was reduced
      significantly after accounting for the different follow-up lengths (I(2)  = 17%,
      P = 0.30), with a 57% (95% confidence interval 46-66%) decrease in the pooled
      incidence of drug injection per 1-year increase in average follow-up.
      CONCLUSIONS: The incidence of drug injection decreases sharply with increasing
      follow-up length in cohort studies on drug injection initiation. Low retention
      rates and potential for downward selection bias in cohort studies on drug
      injection initiation are caused primarily by greater loss to follow-up among
      individuals at higher risk of starting injection, compared with other
      participants.

PMID- 25845978
TI  - A prospective randomized blinded clinical trial: large-volume nasal irrigation
      with fluticasone propionate in the early postoperative period following
      septoplasty.
AB  - BACKGROUND: The aim of this study was to compare 2 methods of nasal irrigation
      after septoplasty. The combined use of low-pressure, high-volume nasal saline
      (LPHVNS) irrigation, together with fluticasone propionate (FP) (LPHVNS+FP), was
      compared with high-pressure, low-volume nasal saline (HPLVNS) irrigation during
      the early postoperative period following septoplasty. METHODS: Seventy-three
      patients undergoing septoplasty for nasal obstruction were recruited for the
      study. The patients were randomly divided into 2 groups; nasal irrigation was
      applied for 4 weeks in both groups. Group 1 (n = 40) used HPLVNS irrigation.
      Group 2 (n = 33) used the LPHVNS+FP combination. The patients were evaluated
      using the visual analogue scale (VAS), Nasal Obstruction Symptom Evaluation
      (NOSE), nasal examination scores, acoustic rhinometry, rhinomanometry, and peak
      nasal inspiratory flowmetry (PNIF) measurements. RESULTS: In group 2, the
      increase in VAS results was more prominent than in group 1. NOSE scores were
      significantly lower in group 2 than in group 1. The nasal examination revealed
      that group 2 had less edema and less crusting than group 1. The decrease in nasal
      airway resistance was significantly higher in group 2. The PNIF values increased
      to a significantly greater extent in group 2 than in group 1. CONCLUSION: Nasal
      irrigation with the LPHVNS+FP combination during the early postoperative period
      following septoplasty is an effective method, resulting not only in increased
      patient satisfaction and nasal air flow but also in decreased edema and crust
      formation.

PMID- 25845979
TI  - Role of c-Myb in chondrogenesis.
AB  - The Myb locus encodes the c-Myb transcription factor involved in controlling a
      broad variety of cellular processes. Recently, it has been shown that c-Myb may
      play a specific role in hard tissue formation; however, all of these results were
      gathered from an analysis of intramembranous ossification. To investigate a
      possible role of c-Myb in endochondral ossification, we carried out our study on
      the long bones of mouse limbs during embryonic development. Firstly, the c-myb
      expression pattern was analyzed by in situ hybridization during endochondral
      ossification of long bones. c-myb positive areas were found in proliferating as
      well as hypertrophic zones of the growth plate. At early embryonic stages,
      localized expression was also observed in the perichondrium and interdigital
      areas. The c-Myb protein was found in proliferating chondrocytes and in the
      perichondrium of the forelimb bones (E14.5-E17.5). Furthermore, protein was
      detected in pre-hypertrophic as well as hypertrophic chondrocytes. Gain-of
      function and loss-of-function approaches were used to test the effect of altered
      c-myb expression on chondrogenesis in micromass cultures established from
      forelimb buds of mouse embryos. A loss-of-function approach using c-myb specific
      siRNA decreased nodule formation, as well as downregulated the level of Sox9
      expression, a major marker of chondrogenesis. Transient c-myb overexpression
      markedly increased the formation of cartilage nodules and the production of
      extracellular matrix as detected by intense staining with Alcian blue. Moreover,
      the expression of early chondrogenic genes such as Sox9, Col2a1 and activity of a
      Col2-LUC reporter were increased in the cells overexpressing c-myb while late
      chondrogenic markers such as Col10a1 and Mmp13 were not significantly changed or
      were downregulated. Taken together, the results of this study demonstrate that
      the c-Myb transcription factor is involved in the regulation and promotion of
      endochondral bone formation. 

PMID- 25845980
TI  - Association of telomere length and mitochondrial DNA copy number in a community
      sample of healthy adults.
AB  - Cellular aging plays a role in longevity and senescence, and has been implicated
      in medical and psychiatric conditions, including heart disease, cancer, major
      depression and posttraumatic stress disorder. Telomere shortening and
      mitochondrial dysfunction are thought to be central to the cellular aging
      process. The present study examined the association between mitochondrial DNA
      (mtDNA) copy number and telomere length in a sample of medically healthy adults.
      Participants (total n=392) were divided into 4 groups based on the presence or
      absence of early life adversity and lifetime psychopathology: No Adversity/No
      Disorder, n=136; Adversity/No Disorder, n=91; No Adversity/Disorder, n=46;
      Adversity/Disorder, n=119. Telomere length and mtDNA copy number were measured
      using quantitative polymerase chain reaction. There was a positive correlation
      between mtDNA and telomere length in the entire sample (r=0.120, p<0.001) and in
      each of the four groups of participants (No Adversity/No Disorder, r=0.291,
      p=0.001; Adversity/No Disorder r=0.279, p=0.007; No Adversity/Disorder r=0.449,
      p=0.002; Adversity/Disorder, r=0.558, p<0.001). These correlations remained
      significant when controlling for age, smoking, and body mass index and establish
      an association between mtDNA and telomere length in a large group of women and
      men both with and without early adversity and psychopathology, suggesting co
      regulation of telomeres and mitochondrial function. The mechanisms underlying
      this association may be important in the pathophysiology of age-related medical
      conditions, such as heart disease and cancer, as well as for stress-associated
      psychiatric disorders. 

PMID- 25845982
TI  - Preliminary investigation of flexibility in learning color-reward associations in
      gibbons (Hylobatidae).
AB  - Previous studies in learning set formation have shown that most animal species
      can learn to learn with subsequent novel presentations being solved in fewer
      presentations than when they first encounter a task. Gibbons (Hylobatidae) have
      generally struggled with these tasks and do not show the learning to learn
      pattern found in other species. This is surprising given their phylogenetic
      position and level of cortical development. However, there have been conflicting
      results with some studies demonstrating higher level learning abilities in these
      small apes. This study attempts to clarify whether gibbons can in fact use
      knowledge gained during one learning task to facilitate performance on a similar,
      but novel problem that would be a precursor to development of a learning set. We
      tested 16 captive gibbons' ability to associate color cues with provisioned food
      items in two experiments where they experienced a period of learning followed by
      experimental trials during which they could potentially use knowledge gained in
      their first learning experience to facilitate solution I subsequent novel tasks.
      Our results are similar to most previous studies in that there was no evidence of
      gibbons being able to use previously acquired knowledge to solve a novel task.
      However, once the learning association was made, the gibbons performed well above
      chance. We found no differences across color associations, indicating learning
      was not affected by the particular color / reward association. However, there
      were variations in learning performance with regard to genera. The hoolock
      (Hoolock leuconedys) and siamang (Symphalangus syndactylus) learned the fastest
      and the lar group (Hylobates sp.) learned the slowest. We caution these results
      could be due to the small sample size and because of the captive environment in
      which these gibbons were raised. However, it is likely that environmental
      variability in the native habitats of the subjects tested could facilitate the
      evolution of flexible learning in some genera. Further comparative study is
      necessary in order to incorporate realistic cognitive variables into foraging
      models.

PMID- 25845981
TI  - Umbilical cord blood transplantation in adults with advanced hodgkin's disease:
      high incidence of post-transplant lymphoproliferative disease.
AB  - We report the outcome of 30 consecutive patients with Hodgkin disease (HD) who
      underwent single-unit UCBT. Most (90%) patients had failed previous autologous
      hematopoietic stem cell transplantation. The conditioning regimens were based on
      combinations of thiotepa, busulfan, cyclophosphamide or fludarabine, and
      antithymocyte globulin. The cumulative incidence (CI) of myeloid engraftment was
      90% [95% confidence interval (C.I.), 74-98%] with a median of 18 d (range, 10
      48). CI of acute graft-versus-host disease (GvHD) grades II-IV was 30% (95% C.I.,
      17-44%), while the incidence of chronic GVHD was 42% (95% C.I., 23-77%). The non
      relapse mortality (NRM) at 100 d and 4 yr was 30% (95% C.I., 13-46%) and 47% (95%
      C.I., 29-65%), respectively. EBV-related post-transplant lymphoproliferative
      disease (EBV-PTLD) accounted for more than one-third of transplant-related death,
      with an estimate incidence of 26% (95% C.I., 9-44). The incidence of relapse at 4
      yr was 25% (95% C.I., 9-42%). Four-year event-free survival (EFS) and overall
      survival (OS) were 28% and 30%, respectively. Despite a high NRM and an
      unexpected high incidence of EBV-PTLD, UCBT in heavily pretreated HD patients is
      an option for patients lacking a suitable adult donor, provided the disease is
      not in refractory relapse. 

PMID- 25845983
TI  - Does kindness matter? Self-compassion buffers the negative impact of diabetes
      distress on HbA1c.
AB  - BACKGROUND: Higher self-compassion is associated with mental and physical health
      benefits in both healthy and chronically ill populations. The current study
      investigated the role of self-compassion in predicting depression, diabetes
      specific distress and HbA1c in patients with diabetes. AIMS: To assess the
      specific operationalization of negative emotionality that best predicted HbA1c
      and to test whether self-compassion would buffer HbA1c in patients with diabetes
      against the negative effects of distress. METHODS: Patients with diabetes (n =
      110) completed measures assessing trait self-compassion, depression and diabetes
      distress. HbA1c results were obtained through medical records. RESULTS: As
      expected, diabetes-specific distress was a better predictor of HbA1c than
      depression; self-compassion moderated the relationship between distress and HbA1c
      such that higher distress predicted higher HbA1c at lower levels of self
      compassion, but not at higher levels of self-compassion. CONCLUSIONS: In addition
      to further demonstrating the link between distress and metabolic outcomes, these
      findings suggest that self-compassion might buffer patients from the negative
      metabolic consequences of diabetes-distress.

PMID- 25845985
TI  - Exposure misclassification due to residential mobility during pregnancy.
AB  - OBJECTIVES: Pregnant women are a highly mobile group, yet studies suggest
      exposure error due to migration in pregnancy is minimal. We aimed to investigate
      the impact of maternal residential mobility on exposure to environmental
      variables (urban fabric, roads and air pollution (PM10 and NO2)) and socio
      economic factors (deprivation) that varied spatially and temporally. METHODS: We
      used data on residential histories for deliveries at >= 24 weeks gestation
      recorded by the Northern Congenital Abnormality Survey, 2000-2008 (n=5399) to
      compare: (a) exposure at conception assigned to maternal postcode at delivery
      versus maternal postcode at conception, and (b) exposure at conception assigned
      to maternal postcode at delivery versus mean exposure based on residences
      throughout pregnancy. RESULTS: In this population, 24.4% of women moved during
      pregnancy. Depending on the exposure variable assessed, 1-12% of women overall
      were assigned an exposure at delivery >1 SD different to that at conception, and
      2-25% assigned an exposure at delivery >1 SD different to the mean exposure
      throughout pregnancy. CONCLUSIONS: To meaningfully explore the subtle
      associations between environmental exposures and health, consideration must be
      given to error introduced by residential mobility.

PMID- 25845984
TI  - Urinary arsenic and insulin resistance in US adolescents.
AB  - Chronic arsenic exposure has been associated with increased diabetes risk in
      adults. Insulin resistance (IR) has been proposed as a mechanism of arsenic
      related diabetes. Although limited evidence in adults found no association
      between arsenic and IR, the association in adolescents is largely unknown. We
      examined the association between urinary arsenic and insulin resistance in US
      adolescents. Eight hundred thirty five adolescents aged 12-19 years, with
      complete data on urinary arsenic (total arsenic, inorganic arsenic and
      dimethylarsenic acid (DMA)), fasting glucose, insulin and key covariates were
      identified from the National Health and Nutrition Examination Survey (NHANES)
      cycles 2003/2004 through 2009/2010. Generalized additive mixed models accounting
      for intra-cluster correlation arising from the complex survey design were used to
      estimate the association between the updated Homeostasis Model Assessment (HOMA2)
      IR and each type of arsenic. After adjusting for potential confounders, including
      urinary creatinine, sociodemographic factors, BMI, waist circumference, and
      arsenobetaine, arsenic exposure was not associated with HOMA2-IR. Interquartile
      range increases in total arsenic, inorganic arsenic and DMA were associated with
      1.5% (95% CI: -2.0, 5.2), 1.1% (95% CI: -1.5, 3.8) and 0.25% (95% CI: -2.3, 2.9)
      increases in HOMA2-IR, respectively. In conclusion, despite arsenic's association
      with diabetes in adults and potential role in insulin resistance, our findings do
      not support the hypothesis that arsenic exposure at levels common in the US
      contributes to insulin resistance in adolescents. Whether higher doses and longer
      exposure duration are required for appreciable influence on insulin resistance,
      or that arsenic does not act through insulin resistance to induce diabetes needs
      further investigation. 

PMID- 25845986
TI  - Childhood asthma and spirometric indices are associated with polymorphic markers
      of two vitamin D 25-hydroxylase genes.
AB  - BACKGROUND: Polymorphic markers of vitamin D pathway genes have been associated
      with asthma traits in different White populations. This study investigated the
      relationship between asthma phenotypes and single nucleotide polymorphisms (SNPs)
      of vitamin D receptor (VDR), vitamin D binding protein (GC), two 25-hydroxylases
      (CYP2R1 and CYP27A1), and 1alpha-hydroxylase (CYP27B1) in Hong Kong Chinese
      children. METHODS: 23 SNPs of the five vitamin D pathway genes were successfully
      genotyped in 914 asthmatic children and 1231 non-allergic controls. Genotypic and
      haplotypic associations with asthma phenotypes (diagnosis, spirometric indices,
      total IgE, and eosinophil percentage) were analyzed by multivariate regression.
      Generalized multifactor dimensionality reduction was used to detect epistatic
      interactions between SNPs for asthma phenotypes. RESULTS: Several SNPs of
      CYP27A1, CYP27B1, GC, and CYP2R1 were associated with asthma or spirometric
      indices, although only the association between FEV1 and CYP2R1 rs7935792 passed
      Bonferroni correction (p = 2.73 * 10(-4) ). Patients with CC genotype of
      rs7935792 had higher FEV1 than those with the other two genotypes. Asthma was
      also associated with TT haplotype of CYP27A1 and AGGATA haplotype of CYP2R1 (p =
      0.021 and 0.024, respectively). Besides, strong association was found between
      FEV1 and GATAG of CYP2R1 (beta = 13.37, p = 4.83 * 10(-4) ). GMDR failed to
      identify any 2-locus to 4-locus interaction that modulated asthma or spirometric
      indices. CONCLUSIONS: Several SNPs and haplotypes of CYP2R1 are associated with
      asthma diagnosis and FEV1 in children. Asthma is also modestly associated with a
      CYP27A1 haplotype. These two 25-hydroxylase genes may be genetic determinants for
      asthma phenotypes in children.

PMID- 25845987
TI  - Pregnancy-associated plasma protein A for prediction of fetal growth restriction.

PMID- 25845989
TI  - Designing versatile heterogeneous catalysts based on Ag and Au nanoparticles
      decorated on chitosan functionalized graphene oxide.
AB  - Herein we report the covalent grafting of chitosan on graphene oxide (GO)
      followed by a simple approach for anchoring silver (AgNPs) and gold (AuNPs)
      nanoparticles onto a chitosan grafted graphene oxide surface by a NaBH4 reduction
      method. Catalytic activity of prepared heterogeneous GO grafted chitosan
      stabilized silver and gold nanocatalysts (GO-Chit-Ag/AuNPs) was explored for the
      reduction of aromatic nitroarenes and degradation of hazardous azo dyes in the
      presence of NaBH4. Both catalysts were found to exhibit excellent catalytic
      activity towards the reduction of aromatic nitroarenes and azo dyes degradation.
      Furthermore, the nanocatalysts were found to be selective towards the reduction
      of nitro groups in halonitroarenes without any dehalogenation under mild
      conditions. 

PMID- 25845988
TI  - Living Composites of Bacteria and Polymers as Biomimetic Films for Metal
      Sequestration and Bioremediation.
AB  - Herein, we report on composite materials of biologically active microorganisms
      placed in a synthetic polymer matrix. These so-called "living composites" were
      utilized for gold sequestration (Micrococcus luteus) and bioremediation of
      nitrite (Nitrobacter winogradskyi) to demonstrate functionality. For the
      preparation of the living composites the bacteria were first encased in a water
      soluble polymer fiber (poly(vinyl alcohol), PVA) followed by coating the fibers
      with a shell of hydrophobic poly(p-xylylene) (PPX) by chemical vapor deposition
      (CVD). The combination of bacteria with polymer materials assured the stability
      and biologically activity of the bacteria in an aqueous environment for several
      weeks. 

PMID- 25845990
TI  - The safety and efficacy of single-agent pemetrexed in platinum-resistant advanced
      urothelial carcinoma: a large single-institution experience.
AB  - BACKGROUND: Pemetrexed is a commonly used treatment for platinum-resistant
      advanced urothelial carcinoma (UC) based on objective response rates of 8% and
      28% in two small phase II studies. To address the discrepancy in reported
      response rates and to assess efficacy and toxicity outside of a clinical trial
      setting, we performed a large retrospective analysis of pemetrexed use at
      Memorial Sloan Kettering Cancer Center. We also investigated candidate prognostic
      factors for overall survival in this setting to explore whether the neutrophil
      lymphocyte ratio (NLR) had independent prognostic significance. PATIENTS AND
      METHODS: Patients receiving pemetrexed for platinum-resistant advanced UC between
      2008 and 2013 were identified. The Response Evaluation Criteria in Solid Tumors
      (RECIST, version 1.1) were used to determine response rate. Kaplan-Meier and Cox
      regression analyses were used to examine the association of various factors with
      efficacy and survival outcomes. Hematologic toxicity and laboratory abnormalities
      were recorded. RESULTS: One hundred and twenty-nine patients were treated with
      pemetrexed. The objective response rate was 5% (95% confidence interval: 1%-9%),
      and the median duration of response was 8 months. Median progression-free
      survival (PFS) was 2.4 months, and the 6-month PFS rate was 14%. There was no
      significant difference in response rate by age, Eastern Cooperative Oncology
      Group (ECOG) performance status, or number of prior therapies. On multivariable
      analysis, ECOG performance status (p < .01), liver metastases (p = .02), and NLR
      (p < .01) had independent prognostic significance for overall survival.
      CONCLUSION: This 129-patient series is the largest reported data set describing
      pemetrexed use in advanced UC. Activity was modest, although discovery of
      molecular biomarkers predictive of response would be valuable to identify the
      small subset of patients who do gain significant benefit. Overall, the data
      highlight the urgent need to develop novel therapies for these patients.

PMID- 25845991
TI  - Salvage systemic therapy for advanced urothelial carcinoma: on the cusp of a sea
      change?

PMID- 25845992
TI  - nab-Paclitaxel in Combination With Weekly Carboplatin With Concurrent
      Radiotherapy in Stage III Non-Small Cell Lung Cancer.
AB  - LESSONS LEARNED: The concomitant use of weekly nab-paclitaxel and carboplatin
      with concurrent radiotherapy was demonstrated to be a safe therapeutic approach
      in this phase I trial of 10 evaluable patients with stage III NSCLC.Despite the
      lack of systemic glucocorticoids, there were no reported infusion reactions or
      cases of peripheral neuropathy in this trial, both of which are known to occur
      with the use of paclitaxel. BACKGROUND: Unresectable stage III non-small cell
      lung cancer (NSCLC) has a 5-year survival rate of 20%, and concurrent
      chemoradiotherapy results in significant toxicity with the use of current
      chemotherapeutic agents. nab-Paclitaxel was approved by the U.S. Food and Drug
      Administration in October 2012 for use along with carboplatin in advanced NSCLC.
      This study was undertaken to determine the maximum tolerated dose and dose
      limiting toxicities (DLTs) of weekly nab-paclitaxel given in combination with
      carboplatin and concurrent radiotherapy in patients with unresectable stage III
      NSCLC. METHODS: Escalating doses of once-weekly nab-paclitaxel were given along
      with once-weekly carboplatin area under the plasma concentration time curve (AUC)
      of 2 and concurrent radiotherapy 66 Gy in 33 fractions, followed by 2 cycles of
      carboplatin and nab-paclitaxel consolidation chemotherapy. RESULTS: Eleven
      patients were enrolled and received treatment per protocol, with 10 evaluable for
      efficacy and toxicity. At dose level 1 (nab-paclitaxel 60 mg/m(2)), 2 DLTs were
      observed: esophagitis and radiation dermatitis. Six patients were enrolled at
      dose level 0 (nab-paclitaxel 40 mg/m(2)) with no DLTs. Nine of 10 evaluable
      patients had a partial response. CONCLUSION: Concurrent chemoradiotherapy with
      nab-paclitaxel 40 mg/m(2) and carboplatin AUC 2 is a safe and well-tolerated
      therapeutic regimen in patients with stage III NSCLC. A separate phase I/II study
      to evaluate the efficacy of this regimen is under way.

PMID- 25845993
TI  - Effects of Fusarium mycotoxins in rations with different concentrate proportions
      on serum haptoglobin and hepatocellular integrity in lactating dairy cows.
AB  - It was hypothesized that long-term intake of a diet contaminated with
      deoxynivalenol (DON) and differing in the proportion of concentrate might affect
      hepatocellular integrity and function as well as biomarkers of systemic
      inflammation in lactating dairy cows. In Period 1 (11 weeks), 26 lactating German
      Holstein cows (13 primiparous and 13 pluriparous, 31 days in milk, 522 kg body
      weight, on average) were divided into two groups and fed diets (50% concentrate)
      with (MYC, n = 12; on average 5.3 mg DON/kg DM) or without (CON, n = 14) DON
      contaminations. In Period 2 (16 weeks), each group was further divided into two
      groups to test whether elevated concentrate proportion as additional burden might
      enhance the toxicity of DON. The cows in MYC60 (n = 6; 4.6 mg DON/kg DM) and
      CON60 (n = 7) received the diet with 60% concentrate, while cows in MYC30 (n = 6;
      4.4 mg DON/kg DM) and CON30 (n = 7) received the diet with 30% concentrate. Blood
      samples were taken in biweekly intervals for activities of aspartate amino
      transferase (AST), glutamate dehydrogenase (GLDH) and gamma-glutamyl transferase
      as well as for concentration of total bilirubin and haptoglobin. Biopsies from
      liver were collected in week 27 for morphological analyses. No DON effect was
      found for the variables assessed in blood. The diet with 60% concentrate led to
      higher activities of AST and GLDH in Period 2. No morphological change was found
      by both light and electron microscopic analyses of liver samples. Results
      indicated that long-term intake of DON-contaminated diet over 27 weeks led to
      neither relevant damages of hepatocytes nor systemic inflammatory responses in
      lactating dairy cows, even if the dietary concentrate proportion was increased to
      60%.

PMID- 25845994
TI  - Matters of fiber size and myonuclear domain: Does size matter more than age?
AB  - INTRODUCTION: The relationship between fiber size and myonuclear content is
      poorly understood. METHODS: Biopsy cross-sections from young and old trained and
      untrained healthy individuals were analyzed for fiber area and myonuclei, and 2
      fiber-size-dependent cluster analyses were performed. RESULTS: When comparing
      fibers of similar size, no effect of training or age was found for myonuclear
      domain. There was a linear relationship between fiber area and myonuclei per
      fiber (r = 0.99; P < 0.001) and a non-linear relationship between fiber area and
      domain (r = 0.97-0.99; P < 0.0001), with a markedly smaller domain in fibers
      <3,000 um(2). A higher proportion of type II fibers <3,000 um(2) was observed in
      the old subjects. CONCLUSIONS: These findings suggest that age-related reductions
      in myonuclear domain size could be explained by the greater proportion of small
      fibers. The data also highlight the usefulness of determining fiber-size-based
      clusters for gaining mechanistic insight into the relationship between skeletal
      muscle fiber size and myonuclear content.

PMID- 25845995
TI  - Evaluating nonindigenous species management in a Bayesian networks derived
      relative risk framework for Padilla Bay, WA, USA.
AB  - Many coastal regions are encountering issues with the spread of nonindigenous
      species (NIS). In this study, we conducted a regional risk assessment using a
      Bayesian network relative risk model (BN-RRM) to analyze multiple vectors of NIS
      introductions to Padilla Bay, Washington, a National Estuarine Research Reserve.
      We had 3 objectives in this study. The 1st objective was to determine whether the
      BN-RRM could be used to calculate risk from NIS introductions for Padilla Bay.
      Our 2nd objective was to determine which regions and endpoints were at greatest
      risk from NIS introductions. Our 3rd objective was to incorporate a management
      option into the model and predict endpoint risk if it were to be implemented.
      Eradication can occur at different stages of NIS invasions, such as the
      elimination of these species before being introduced to the habitat or removal of
      the species after settlement. We incorporated the ballast water treatment
      management scenario into the model, observed the risk to the endpoints, and
      compared this risk with the initial risk estimates. The model results indicated
      that the southern portion of the bay was at greatest risk because of NIS. Changes
      in community composition, Dungeness crab, and eelgrass were the endpoints most at
      risk from NIS introductions. The currents node, which controls the exposure of
      NIS to the bay from the surrounding marine environment, was the parameter that
      had the greatest influence on risk. The ballast water management scenario
      displayed an approximate 1% reduction in risk in this Padilla Bay case study. The
      models we developed provide an adaptable template for decision makers interested
      in managing NIS in other coastal regions and large bodies of water.

PMID- 25845996
TI  - Inherent organic compounds in biochar--Their content, composition and potential
      toxic effects.
AB  - Pyrolysis liquids consist of thermal degradation products of biomass in various
      stages of its decomposition. Therefore, if biochar gets affected by re-condensed
      pyrolysis liquids it is likely to contain a huge variety of organic compounds. In
      this study the chemical composition of such compounds associated with two
      contaminated, high-volatile organic compound (VOC) biochars were investigated and
      compared with those for a low-VOC biochar. The water-soluble organic compounds
      with the highest concentrations in the two high-VOC biochars were acetic, formic,
      butyric and propionic acids; methanol, phenol, o-, m- and p-cresol, and 2,4
      dimethylphenol, all with concentrations over 100 MUg g(-1). The concentrations of
      16 US EPA PAHs determined by 36 h toluene extractions were 6.09 MUg g(-1) for the
      low-VOC biochar. For high-VOC biochar the total concentrations were 53.42 MUg g(
      1) and 27.89 MUg g(-1), while concentrations of water-soluble PAHs ranged from
      1.5 to 2 MUg g(-1). Despite the concentrations of PAHs exceeding biochar
      guideline values, it was concluded that, for these particular biochars, the
      biggest concern for application to soil would be the co-occurrence of VOCs such
      as low molecular weight (LMW) organic acids and phenols, as these can be highly
      mobile and have a high potential to cause phytotoxic effects. Therefore, based on
      results of this study we strongly suggest for VOCs to be included among criteria
      for assessment of biochar quality. 

PMID- 25845997
TI  - Dissolved organic matter removal during coal slag additive soil aquifer treatment
      for secondary effluent recharging: Contribution of aerobic biodegradation.
AB  - Recycling wastewater treatment plant (WWTP) effluent at low cost via the soil
      aquifer treatment (SAT), which has been considered as a renewable approach in
      regenerating potable and non-potable water, is welcome in arid and semi-arid
      regions throughout the world. In this study, the effect of a coal slag additive
      on the bulk removal of the dissolved organic matter (DOM) in WWTP effluent during
      SAT operation was explored via the matrix configurations of both coal slag layer
      and natural soil layer. Azide inhibition and XAD-resins fractionation experiments
      indicated that the appropriate configuration designing of an upper soil layer (25
      cm) and a mixture of soil/coal slag underneath would enhance the removal
      efficiency of adsorption and anaerobic biodegradation to the same level as that
      of aerobic biodegradation (31.7% vs 32.2%), while it was only 29.4% compared with
      the aerobic biodegradation during traditional 50 cm soil column operation. The
      added coal slag would preferentially adsorb the hydrophobic DOM, and those
      adsorbed organics could be partially biodegraded by the biomass within the SAT
      systems. Compared with the relatively lower dissolved organic carbon (DOC),
      ultraviolet light adsorption at 254 nm (UV-254) and trihalomethane formation
      potential (THMFP) removal rate of the original soil column (42.0%, 32.9%, and
      28.0%, respectively), SSL2 and SSL4 columns would enhance the bulk removal
      efficiency to more than 60%. Moreover, a coal slag additive in the SAT columns
      could decline the aromatic components (fulvic-like organics and tryptophan-like
      proteins) significantly. 

PMID- 25845998
TI  - Effect of weathering transformations of coal combustion residuals on trace
      elements mobility in view of the environmental safety and sustainability of their
      disposal and use. II. Element release.
AB  - This paper is the second one of two companion papers. It presents results of a
      study aimed at assessing the effect of real time weathering transformations of
      Coal Combustion Residuals (CCRs) on trace element binding/release and its
      environmental implications. The study is based on the chemical composition of
      pore solutions extracted from primary alkaline Class F CCRs, 0 to >40 years old,
      sampled from the surface layer and vertical profiles at four selected typical
      CCRs impoundments. The long-term weathering transformations were found to lead to
      gradual acidification to pH < 4 of this primary alkaline material, due to
      internal processes of mineral formation/dissolution. Direct analysis of the pore
      solutions and a statistical analysis have shown different susceptibility of many
      trace elements to release during internal acidification processes occurring at
      consecutive Wash-out I (pH > 8), Dissolution II (8 >= pH >= 7) and Delayed
      Release III (pH < 7) stages of weathering compared to that at external sources of
      pH. The elements occurring in the CCRs are represented by three major groups
      showing the highest release to pore water: (a) within the acidic pH range (Na, K,
      Zn, Fe, Cd, Mo, Cr, B, Mn, Be and Ni; (b) within the near-neutral pH range (Al,
      V, Ba, Cu and Ag) and also Sb, Hg and Co not analyzed at pH < 7; (c) within the
      alkaline pH range (Ca, Mg, Pb, As, Se, Tl). Elements whose concentrations
      exceeded the threshold values for good chemical status of groundwater (TVs) at
      all weathering stages over the entire pH range studied were K, Al, B, Cr, Mo, V,
      As, Se, Sb and Hg, while Na, Zn, Fe and Cd showed particularly high delayed
      release at pH < 7, thus confirming the need of a precautionary approach to CCRs
      uncontrolled disposal and bulk reuse as common fill in view of long term
      environmental safety and sustainability. 

PMID- 25845999
TI  - Central sorting and recovery of MSW recyclable materials: A review of
      technological state-of-the-art, cases, practice and implications for materials
      recycling.
AB  - Today's waste regulation in the EU comprises stringent material recovery targets
      and calls for comprehensive programs in order to achieve them. A similar movement
      is seen in the US where more and more states and communities commit to high
      diversion rates from landfills. The present paper reviews scientific literature,
      case studies and results from pilot projects, on the topic of central sorting of
      recyclable materials commonly found in waste from households. The study
      contributes, inter alia, with background understanding on the development of
      materials recovery, both in a historical and geographical perspective. Physical
      processing and sorting technology has reached a high level of maturity, and many
      quality issues linked to cross-contamination by commingling have been
      successfully addressed to date. New sorting plants tend to benefit from economies
      of scale, and innovations in automation and process control, which are targeted
      at curtailing process inefficiencies shown by operational practice. Technology
      developed for the sorting of commingled recyclables from separate collection is
      also being successfully used to upgrade residual MSW processing plants. The
      strongest motivation for central sorting of residual MSW is found for areas where
      source separation and separate collection is difficult, such as urban
      agglomerations, and can in such areas contribute to increasing recycling rates,
      either complementary to- or as a substitute for source separation of certain
      materials, such as plastics and metals. 

PMID- 25846000
TI  - Modeling, kinetic, and equilibrium characterization of paraquat adsorption onto
      polyurethane foam using the ion-pairing technique.
AB  - We studied the adsorption of paraquat onto polyurethane foam (PUF) when it was in
      a medium containing sodium dodecylsulfate (SDS). The adsorption efficiency was
      dependent on the concentration of SDS in solution, because the formation of an
      ion-associate between the cationic paraquat and the dodecylsulfate anion was
      found to be a fundamental step in the process. A computational study was carried
      out to identify the possible structure of the ion-associate in aqueous medium.
      The obtained data demonstrated that the structure is probably formed from four
      units of dodecylsulfate bonded to one paraquat moiety. The results showed that
      94% of the paraquat present in 45 mL of a solution containing 3.90 * 10(-5) mol
      L(-1) could be retained by 300 mg of PUF, resulting in the removal of 2.20 mg of
      paraquat. The experimental data were reasonably adjusted to the Freundlich
      isotherm and to the pseudo-second-order kinetic model. Also, the application of
      Morris-Weber and Reichenberg models indicated that both film-diffusion and
      intraparticle-diffusion processes were active during the control of the
      adsorption kinetics. 

PMID- 25846001
TI  - Valuing the commons: An international study on the recreational benefits of the
      Baltic Sea.
AB  - The Baltic Sea provides benefits to all of the nine nations along its coastline,
      with some 85 million people living within the catchment area. Achieving
      improvements in water quality requires international cooperation. The likelihood
      of effective cooperation is known to depend on the distribution across countries
      of the benefits and costs of actions needed to improve water quality. In this
      paper, we estimate the benefits associated with recreational use of the Baltic
      Sea in current environmental conditions using a travel cost approach, based on
      data from a large, standardized survey of households in each of the 9 Baltic Sea
      states. Both the probability of engaging in recreation (participation) and the
      number of visits people make are modeled. A large variation in the number of
      trips and the extent of participation is found, along with large differences in
      current annual economic benefits from Baltic Sea recreation. The total annual
      recreation benefits are close to 15 billion EUR. Under a water quality
      improvement scenario, the proportional increases in benefits range from 7 to 18%
      of the current annual benefits across countries. Depending on how the costs of
      actions are distributed, this could imply difficulties in achieving more
      international cooperation to achieve such improvements. 

PMID- 25846002
TI  - CO2 sequestration using accelerated gas-solid carbonation of pre-treated EAF
      steel-making bag house dust.
AB  - Mineral CO2 sequestration is a promising process for the reduction of carbon
      dioxide emissions to the atmosphere. In this paper, alkaline calcium-rich dust
      particles collected from bag filters of electric arc furnaces (EAF) for steel
      making were utilized as a viable raw material for mineral CO2 sequestration. The
      dust particles were pre-treated through hydration, drying and screening. The pre
      treated particles were then subjected to direct gas-solid carbonation reaction in
      a fluidized-bed reactor. The carbonated products were characterized to determine
      the overall sequestration capacity and the mineralogical structures. Leaching
      tests were also performed to measure the extracted minerals from the carbonated
      dust and evaluate the carbonation process on dust stabilization. The experimental
      results indicated that CO2 could be sequestered using the pre-treated bag house
      dust. The maximum sequestration of CO2 was 0.657 kg/kg of dust, based on the
      total calcium content. The highest degree of carbonation achieved was 42.5% and
      the carbonation efficiency was 69% at room temperature. 

PMID- 25846003
TI  - Hydrotalcite-TiO2 magnetic iron oxide intercalated with the anionic surfactant
      dodecylsulfate in the photocatalytic degradation of methylene blue dye.
AB  - The new magnetic photocatalysts HT/TiO2/Fe and HT-DS/TiO2/Fe, modified with the
      anionic surfactant sodium dodecylsulfate (DS) were successfully synthesized in
      this work. Titanium dioxide (anatase) followed by iron oxide were deposited on
      the hydrotalcite support. Several catalyst samples were prepared with different
      amounts of titanium and iron. The photocatalysts were characterized by infrared
      and Raman spectroscopy, X-ray diffraction, scanning electron microscopy.
      Photocatalytic performance was analyzed by UV-visible radiation (filter cutoff,
      lambda > 300 nm) of an aqueous solution (24 mg/L) of methylene blue (MB). The
      most efficient catalyst was obtained at an iron oxide:TiO2 molar ratio of 2:3.
      This catalyst showed high photocatalytic activity, removing 96% of the color and
      61% of total organic carbon from the MB solution after 120 min. It was easily
      removed from solution after use because of its magnetic properties. The reuse of
      the HT-DS/TiO2/Fe23 catalyst was viable and the catalyst was structurally stable
      for at least four consecutive photocatalytic cycles. 

PMID- 25846004
TI  - Protective activity of carnosine and anserine against zinc-induced neurotoxicity:
      a possible treatment for vascular dementia.
AB  - Carnosine (beta-alanyl-L-histidine) is a small dipeptide with numerous beneficial
      effects, including the maintenance of the acid-base balance, antioxidant
      properties, chelating agent, anti-crosslinking, and anti-glycation activities.
      High levels of carnosine and its analogue anserine (1-methyl carnosine) are found
      in skeletal muscle and the brain. Zinc (Zn)-induced neurotoxicity plays a crucial
      role in the pathogenesis of vascular dementia (VD), and carnosine inhibits Zn
      induced neuronal death. Here, the protective activity of carnosine against Zn
      induced neurotoxicity and its molecular mechanisms such as cellular Zn influx and
      Zn-induced gene expression were investigated using immortalised hypothalamic
      neurons (GT1-7 cells). Carnosine and anserine protected against Zn-induced
      neurotoxicity not by preventing increases in intracellular Zn(2+) but by
      participating in the regulation of the endoplasmic reticulum (ER) stress pathway
      and the activity-regulated cytoskeletal protein (Arc). Accordingly, carnosine and
      anserine protected against neurotoxicity induced by ER-stress inducers
      thapsigargin and tunicamycin. Hence, carnosine and anserine are expected to have
      future therapeutic potential for VD and other neurodegenerative diseases.

PMID- 25846005
TI  - Structural analysis of the polo-box domain of human Polo-like kinase 2.
AB  - Polo-like kinases (Plks) are the key regulators of cell cycle progression, the
      members of which share a kinase domain and a polo-box domain (PBD) that serves as
      a protein-binding module. While Plk1 is a promising target for antitumor therapy,
      Plk2 is regarded as a tumor suppressor even though the two Plks commonly
      recognize the S-pS/T-P motif through their PBD. Herein, we report the crystal
      structure of the PBD of Plk2 at 2.7 A. Despite the overall structural similarity
      with that of Plk1 reflecting their high sequence homology, the crystal structure
      also contains its own features including the highly ordered loop connecting two
      subdomains and the absence of 310 -helices in the N-terminal region unlike the
      PBD of Plk1. Based on the three-dimensional structure, we furthermore could model
      its interaction with two types of phosphopeptides, one of which was previously
      screened as the optimal peptide for the PBD of Plk2.

PMID- 25846006
TI  - AMPK Activation Affects Glutamate Metabolism in Astrocytes.
AB  - Mammalian AMP-activated protein kinase (AMPK) functions as a metabolic switch. It
      is composed of 3 different subunits and its activation depends on phosphorylation
      of a threonine residue (Thr172) in the alpha-subunit. This phosphorylation can be
      brought about by 5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside (AICAR)
      which in the cells is converted to a monophosphorylated nucleotide mimicking the
      effect of AMP. We show that the preparation of cultured astrocytes used for
      metabolic studies expresses AMPK, which could be phosphorylated by exposure of
      the cells to AICAR. The effect of AMPK activation on glutamate metabolism in
      astrocytes was studied using primary cultures of these cells from mouse cerebral
      cortex during incubation in media containing 2.5 mM glucose and 100 uM [U
      (13)C]glutamate. The metabolism of glutamate including a detailed analysis of its
      metabolic pathways involving the tricarboxylic acid (TCA) cycle was studied using
      high-performance liquid chromatography analysis supplemented with gas
      chromatography-mass spectrometry technology. It was found that AMPK activation
      had profound effects on the pathways involved in glutamate metabolism since the
      entrance of the glutamate carbon skeleton into the TCA cycle was reduced. On the
      other hand, glutamate uptake into the astrocytes as well as its conversion to
      glutamine catalyzed by glutamine synthetase was not affected by AMPK activation.
      Interestingly, synthesis and release of citrate, which are hallmarks of
      astrocytic function, were affected by a reduction of the flux of glutamate
      derived carbon through the malic enzyme and pyruvate carboxylase catalyzed
      reactions. Finally, it was found that in the presence of glutamate as an
      additional substrate, glucose metabolism monitored by the use of tritiated
      deoxyglucose was unaffected by AMPK activation. Accordingly, the effects of AMPK
      activation appeared to be specific for certain key processes involved in
      glutamate metabolism. 

PMID- 25846007
TI  - mTOR and Erk1/2 Signaling in the Cerebrospinal Fluid-Contacting Nucleus is
      Involved in Neuropathic Pain.
AB  - The cerebrospinal fluid-contacting nucleus (CSF-CN) has been demonstrated to be
      involved in neuropathic pain, but the underlying molecular mechanisms remain
      unclear. Previous work has shown that mTOR and ERK1/2 are important signaling
      pathways regulating neuropathic pain. However, studies on the interactions
      between these major pathways in neuropathic pain are very rare. Therefore, the
      purpose of this study is to determine whether mTOR and ERK1/2 exist in the CSF-CN
      and elucidate their alterations in neuropathic pain, especially, the crosstalk
      between them. Our results showed that mTOR and ERK1/2 were distributed in the CSF
      CN, and their expression levels were increased in chronic constriction injury
      (CCI)-induced neuropathic pain. Furthermore, the injection of both the mTOR
      antagonist rapamycin and the ERK1/2 antagonist U0126 into the lateral ventricle
      of the brain attenuated CCI-induced neuropathic pain. Inhibition of the ERK1/2
      pathway had little impact on mTOR signaling, but inhibition of the mTOR pathway
      significantly increased ERK/2 signaling. The coadministration of rapamycin and
      U0126 inhibited the rapamycin-induced upregulation of ERK, and had a greater
      effect on pain behaviors than did the single-drug administrations. These data
      extend our understanding of the relationship between mTOR and ERK in the
      supraspinal site and demonstrate that the CSF-CN participates in neuropathic pain
      via the regulation of mTOR and ERK1/2.

PMID- 25846008
TI  - Activation of mGluR5 Attenuates Microglial Activation and Neuronal Apoptosis in
      Early Brain Injury After Experimental Subarachnoid Hemorrhage in Rats.
AB  - Activation of metabotropic glutamate receptor 5 (mGluR5) provided neuroprotection
      in multiple central nervous system injury, but the roles of mGluR5 in
      subarachnoid hemorrhage (SAH) remain unclear. In present study, we aimed to
      evaluate whether activation of mGluR5 attenuates early brain injury (EBI) after
      experimental SAH in rats. We found that selective mGluR5 orthosteric agonist CHPG
      or positive allosteric modulator VU0360172 administration significantly improves
      neurological function and attenuates brain edema at 24 h after SAH. Furthermore,
      mGluR5 obviously expresses in activated microglia (ED-1 positive) after SAH. CHPG
      or VU0360172 administration significantly reduces the numbers of activated
      microglia and the protein and mRNA levels of pro-inflammatory cytokines IL-1beta,
      IL-6 and TNF-alpha at 24 h after SAH. Moreover, CHPG or VU0360172 administration
      obviously reduces the number of TUNEL-positive cells and active caspase-3/NeuN
      positive neurons in cortex at 24 h after SAH. CHPG or VU0360172 administration
      significantly up-regulates the expression of Bcl-2, and down-regulates the
      expression of Bax and active caspase-3, which in turn increases the ratio of Bcl
      2/Bax. Our results indicate that activation of mGluR5 attenuates microglial
      activation and neuronal apoptosis, and improves neurological function in EBI
      after SAH.

PMID- 25846009
TI  - Synthesis and Evaluation of New 4-Chloro-2-(3-chloro-4-fluorophenyl)-5
      (aliphatic/cyclic saturated amino)pyridazin-3(2H)-one Derivatives as Anticancer,
      Antiangiogenic, and Antioxidant Agents.
AB  - Pyridazinones are widely recognized as versatile scaffolds with a wide spectrum
      of biological activities. In the present work, a series of new 4-chloro-2-(3
      chloro-4-fluorophenyl)-5-(aliphatic/cyclic saturated amino)pyridazin-3(2H)-one
      derivatives 4a-i were synthesized and characterized by spectral techniques. The
      inhibitory effects of the synthesized compounds 4a-i on the viability of three
      human cancer cell lines, HEP3BPN 11 (liver), MDA 453 (breast), and HL 60
      (leukemia), were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) reduction assay. Among the compounds 4a-i
      screened, 4g and 4i exhibited inhibitory activity very close to the standard
      methotrexate; therefore, these lead compounds were further tested for their
      potential to inhibit the proangiogenic cytokines involved in tumor progression.
      Compound 4g was found to be a potent antiangiogenic agent against TNFalpha, VEGF,
      FGFb, and TGFbeta, whereas 4i showed potent antiangiogenic activity against
      TNFalpha, VEGF, FGFb, and leptin. All the compounds 4a-i were screened for their
      antioxidant activities using 2,2-diphenyl-1-picryl hydrazine (DPPH), OH, and
      superoxide anion radicals. Compound 4f showed better OH radical scavenging
      activity than the standard ascorbic acid.

PMID- 25846010
TI  - Stressful life events preceding the onset of depression in Asian patients with
      major depressive disorder.
AB  - BACKGROUND: Previous studies have identified the significant role of stressful
      life events in the onset of depressive episodes. However, there is a paucity of
      cross-national studies on stressful life events that precede depression. AIMS: We
      aimed to compare types of stressful life events associated with the onset of
      depressive episodes in patients with major depressive disorder (MDD) in five
      Asian countries. METHOD: A total of 507 outpatients with MDD were recruited in
      China (n = 114), South Korea (n = 101), Malaysia (n = 90), Thailand (n = 103) and
      Taiwan (n = 99). All patients were assessed with the Mini-International
      Neuropsychiatric Interview and the List of Threatening Experiences. The
      prevalence of each type of stressful life events was calculated and compared
      between each country. RESULTS: The type of stressful life event that preceded the
      onset of a depressive episode differed between patients in China and Taiwan and
      those in South Korea, Malaysia and Thailand. Patients in China and Taiwan were
      less likely to report interpersonal relationship problems and
      occupational/financial problems than patients in South Korea, Malaysia and
      Thailand. CONCLUSION: Understanding the nature and basis of culturally determined
      susceptibilities to specific stressful life events is critical for establishing a
      policy of depression prevention and providing effective counseling services for
      depressed patients.

PMID- 25846011
TI  - A novel cisplatin mediated apoptosis pathway is associated with acid
      sphingomyelinase and FAS proapoptotic protein activation in ovarian cancer.
AB  - Platinum-based anticancer drugs, including cisplatin and carboplatin, have been
      cornerstones in the treatment of solid tumors. We report here that these DNA
      damaging agents, particularly cisplatin, induce apoptosis through plasma membrane
      disruption, triggering FAS death receptor via mitochondrial (intrinsic) pathways.
      Our objectives were to: quantify the composition of membrane metabolites; and
      determine the potential involvement of acid sphingomyelinase (ASMase) in the FAS
      mediated apoptosis in ovarian cancer after cisplatin treatment. The resulting
      analysis revealed enhanced apoptosis as measured by: increased phosphocholine,
      and glycerophosphocholine; elevated cellular energetics; and phosphocreatine and
      nucleoside triphosphate concentrations. The plasma membrane alterations were
      accompanied by increased ASMase activity, leading to the upregulation of FAS,
      FASL and related pro-apoptotic BAX and PUMA genes. Moreover FAS, FASL, BAX, PUMA,
      CASPASE-3 and -9 proteins were upregulated. Our findings implicate ASMase
      activity and the intrinsic pathways in cisplatin-mediated membrane demise, and
      contribute to our understanding of the mechanisms by which ovarian tumors may
      become resistant to cisplatin. 

PMID- 25846012
TI  - No trade-off between high and low temperature tolerance in a winter acclimatized
      Danish Drosophila subobscura population.
AB  - Coping with cold winter conditions is a major challenge for many insects. In
      early spring we observed newly emerged Drosophila subobscura, which had
      overwintered as larvae and pupae. As temperatures increase during spring these
      flies are faced with higher minimum and maximum temperatures in their natural
      microhabitat. Thus, there is a potential costly mismatch between winter and early
      spring acclimatization and the increased ambient temperatures later in adult
      life. We obtained individuals from a natural Danish population of D. subobscura
      and acclimated them in the laboratory to 20  degrees C for one generation, and
      compared critical thermal maximum (CTmax) and minimum (CTmin) to that of
      individuals collected directly from their natural microhabitat. The two
      populations (laboratory and field) were subsequently both held in the laboratory
      at 20  degrees C and tested for their CTmax and CTmin every third day for 28
      days. At the first day of testing, field acclimatized D. subobscura had both
      higher heat and cold resistance compared to laboratory flies, and thereby a
      considerable larger thermal scope. Following transfer to the laboratory, cold and
      heat resistance of the field flies decreased over time relative to the laboratory
      flies. Despite the substantial decrease in thermal tolerances the thermal scope
      remained larger for field acclimatized individuals for the duration of the
      experiment. We conclude that flies acclimatized to their natural microhabitat had
      increased cold resistance, without a loss in heat tolerance. Thus while a
      negative correlation between cold and heat tolerance is typically observed in
      laboratory studies in Drosophila sp., this was not observed for field
      acclimatized D. subobscura in this study. We suggest that this is an adaptation
      to juvenile overwintering in temperate cold environments, where developmental
      (winter) temperatures can be much lower than temperatures experienced by
      reproducing adults after emergence (spring). The ability to gain cold tolerance
      through acclimatization without a parallel loss of heat tolerance affects thermal
      scope and suggests that high and low thermal tolerance act through mechanisms
      with different dynamics and reversibility.

PMID- 25846013
TI  - Chill-tolerant Gryllus crickets maintain ion balance at low temperatures.
AB  - Insect cold tolerance is both phenotypically-plastic and evolutionarily labile,
      but the mechanisms underlying this variation are uncertain. Chill-susceptible
      insects lose ion and water homeostasis in the cold, which contributes to the
      development of injuries and eventually death. We thus hypothesized that more cold
      tolerant insects will better maintain ion and water balance at low temperatures.
      We used rapid cold-hardening (RCH) and cold acclimation to improve cold tolerance
      of male Gryllus pennsylvanicus, and also compared this species to its cold
      tolerant relative (Gryllus veletis). Cold acclimation and RCH decreased the
      critical thermal minimum (CTmin) and chill coma recovery time (CCR) in G.
      pennsylvanicus, but while cold acclimation improved survival of 0  degrees C, RCH
      did not; G. veletis was consistently more cold-tolerant (and had lower CCR and
      CTmin) than G. pennsylvanicus. During cold exposure, hemolymph water and Na(+)
      migrated to the gut of warm-acclimated G. pennsylvanicus, which increased
      hemolymph [K(+)] and decreased muscle K(+) equilibrium potentials. By contrast,
      cold-acclimated G. pennsylvanicus suffered a smaller loss of ion and water
      homeostasis during cold exposure, and this redistribution did not occur at all in
      cold-exposed G. veletis. The loss of ion and water balance was similar between
      RCH and warm-acclimated G. pennsylvanicus, suggesting that different mechanisms
      underlie decreased CCR and CTmin compared to increased survival at 0  degrees C.
      We conclude that increased tolerance of chilling is associated with improved
      maintenance of ion and water homeostasis in the cold, and that this is consistent
      for both phenotypic plasticity and evolved cold tolerance.

PMID- 25846014
TI  - Ledipasvir-sofosbuvir plus ribavirin for patients with genotype 1 hepatitis C
      virus previously treated in clinical trials of sofosbuvir regimens.
AB  - Patients who fail to achieve sustained virological response (SVR) after treatment
      with sofosbuvir (SOF) plus ribavirin (RBV) with or without pegylated interferon
      (Peg-IFN) do not have established retreatment options. We conducted an open-label
      trial to assess the efficacy and safety of ledipasvir (LDV)-SOF plus RBV in
      patients with genotype 1 hepatitis C virus (HCV) who did not achieve SVR after
      treatment in phase II and III trials of SOF regimens. We enrolled 51 patients at
      24 sites in the United States. All patients received the fixed-dose combination
      tablet of LDV-SOF once-daily plus weight-based RBV (1,000 or 1,200 mg/day) for 12
      weeks. The efficacy endpoint was the proportion of patients with SVR 12 weeks
      after discontinuation of therapy (SVR12). Of the 51 patients enrolled, 25 (49%)
      had previously received SOF plus Peg-IFN-RBV, 20 (39%) had received SOF-RBV, 5
      (10%) had received SOF placebo plus Peg-IFN-RBV, and 1 (2%) received GS-0938
      monotherapy. Fourteen (27%) had compensated cirrhosis at baseline, and 47 (92%)
      had non-CC interleukin-28B genotypes. SVR12 was achieved by 50 of the 51 patients
      (98%) treated. Among the 45 patients who received SOF in earlier treatment, 44
      (98%) achieved SVR12. The only patient who did not achieve SVR12 was a patient
      with genotype 3a HCV who had been incorrectly genotyped as 1a in the previous
      study. Given the high rates of SVR12, no differences among patient subgroups were
      discernible. Of 51 patients, 41 (80%) experienced at least one adverse event
      (AE), but most events were mild to moderate in severity. The most common AEs were
      fatigue, headache, and diarrhea. One patient discontinued treatment because of an
      unrelated AE (bipolar disorder). CONCLUSION: Twelve weeks of LDV-SOF plus RBV was
      an effective and safe treatment for patients who have not achieved SVR with
      earlier regimens that included SOF.

PMID- 25846015
TI  - A combined morphometric analysis of foot form and its association with sex,
      stature, and body mass.
AB  - OBJECTIVES: Morphometric analysis of footprints is a classic means for orthopedic
      diagnosis. In forensics and physical anthropology, it is commonly used for the
      estimation of stature and body mass. We studied individual variation and sexual
      dimorphism of foot dimensions and footprint shape by a combination of classic
      foot measurements and geometric morphometric methods. METHODS: Left and right
      feet of 134 healthy adult males and females were scanned twice with a 3D optical
      laser scanner, and stature as well as body mass were recorded. Foot length and
      width were measured on the 3D scans. The 2D footprints were extracted as the
      plantar-most 2 mm of the 3D scans and measured with 85 landmarks and
      semilandmarks. RESULTS: Both foot size and footprint shape are sexually dimorphic
      and relate to stature and body mass. While dimorphism in foot length largely
      results from dimorphism in stature, dimorphism in footprint shape partly owes to
      the dimorphism in BMI. Stature could be estimated well based on foot length (R(2)
      = 0.76), whereas body mass was more closely related to foot width (R(2)  =
      0.62). Sex could be estimated correctly for 95% of the individuals based on a
      combination of foot width and length. DISCUSSION: Geometric morphometrics proved
      to be an effective tool for the detailed analysis of footprint shape. However,
      for the estimation of stature, body mass, and sex, shape variables did not
      considerably improve estimates based on foot length and width.

PMID- 25846016
TI  - A person-centered approach to adolescent emotion regulation: Associations with
      psychopathology and parenting.
AB  - Adolescence is a unique period of heightened emotional arousal and still
      developing regulatory abilities. Adolescent emotion regulation patterns may be
      critically involved in adolescents' psychosocial development, but patterns of
      emotion regulation in youths are not well understood. The current study used
      latent profile analysis (LPA) to elucidate patterns of emotion expression,
      experience, and emotion-related physiological arousal in adolescents. A sample of
      198 adolescents and their primary caregivers participated in an emotionally
      arousing parent-adolescent conflict interaction. Adolescents' observed emotion
      expressions, emotion experiences, and heart rate (HR) and caregiver parenting
      behaviors were assessed during and/or after the interaction. Parents reported on
      adolescents' internalizing and externalizing symptoms, and youths reported on
      depressive symptoms. The LPA revealed four emotion regulation profiles: a
      moderate HR and high expression profile, a suppression profile (with low negative
      emotion expression and high emotion experience), a low reactive profile, and a
      high reactive profile. The moderate HR and high expression profile was associated
      with lower conduct disorder symptoms, the suppression profile was related to
      lower anxiety symptoms, and the high reactive profile was associated with higher
      adolescent depressive symptoms. The high reactive profile and moderate HR and
      high expression profile were associated with more negative/critical parenting
      behaviors. Findings suggest that profiles of adolescent emotion regulation can be
      empirically identified and may be significant risk factors for psychopathology. 

PMID- 25846017
TI  - Progressive outer retinal necrosis in immunocompromised kidney allograft
      recipient.
AB  - Ocular complications in patients who underwent renal transplantation are
      attributed to side effects of the immunosuppressive regimen. Progressive outer
      retinal necrosis (PORN) syndrome is a clinical variant of necrotizing herpetic
      retinopathy and it occurs almost exclusively in patients with acquired
      immunodeficiency syndrome. We present a case of a human immunodeficiency virus
      negative patient who underwent renal transplant and, after a few years, developed
      bilateral PORN associated with viral infections. Varicella zoster virus (VZV) and
      BK virus were identified by polymerase chain reaction from the vitreous fluid. It
      is unclear which of the viruses identified had the dominant role in the
      pathogenesis of PORN and other organ damage, or whether their actions were
      synergistic. Adequate antiviral immune surveillance, as well as pre-transplant
      vaccination against VZV, may reduce the incidence of VZV infection and its
      complications.

PMID- 25846018
TI  - Mental health care use in relation to depressive symptoms among pregnant women in
      the USA.
AB  - We examined mental health care use in relation to depressive symptoms (Patient
      Health Questionnaire (PHQ-9) >= 10) among a nationally representative sample of
      pregnant women using data from the National Health and Nutrition Examination
      Survey 2005-2012. Logistic regression models estimated crude and adjusted odds
      ratios for mental health care use in the past year in relation to depressive
      symptoms. While 8.2 % (95 % CI 4.6-11.8) of pregnant women were depressed, only
      12 % (95 % CI 1.8-22.1) of these women reported mental health care use in the
      past year.

PMID- 25846026
TI  - Attenuation of Porphyromonas gingivalis oral infection by alpha-amylase and
      pentamidine.
AB  - The Porphyromonas gingivalis bacterium is one of the most influential pathogens
      in oral infections. In the current study, the antimicrobial activity of alpha
      amylase and pentamidine against Porphyromonas gingivalis was evaluated. Their in
      vitro inhibitory activity was investigated with the agar overlay technique, and
      the minimal inhibitory and bactericidal concentrations were determined. Using the
      bactericidal concentration, the antimicrobial actions of the inhibitors were
      investigated. In the present study, multiple techniques were utilized, including
      scanning electron microscopy (SEM), general structural analysis and differential
      gene expression analysis. The results obtained from SEM and bactericidal analysis
      indicated a notable observation; the pentamidine and alpha-amylase treatment
      destroyed the structure of the bacterial cell membranes, which led to cell death.
      These results were used to further explore these inhibitors and the mechanisms by
      which they act. Downregulated expression levels were observed for a number of
      genes coding for hemagglutinins and gingipains, and various genes involved in
      hemin uptake, chromosome replication and energy production. However, the
      expression levels of genes associated with iron storage and oxidative stress were
      upregulated by alpha-amylase and pentamidine. A greater effect was noted in
      response to pentamidine treatment. The results of the present study demonstrate
      promising therapeutic potential for alpha-amylases and pentamidine. These
      molecules have the potential to be used to develop novel drugs and broaden the
      availability of pharmacological tools for the attenuation of oral infections
      caused by Porphyromonas gingivalis.

PMID- 25846027
TI  - Re: Editorial Comment on Clinical Performance of Serum Isoform (-2)proPSA (p2PSA)
      and its Derivatives, Namely %p2PSA and PHI (Prostate Health Index) in Men Younger
      than 60 Years of Age: Results from a Multicentric European Study: S. S. Taneja J
      Urol 2014;192:421.

PMID- 25846029
TI  - Methodological challenges when performing a systematic review.
AB  - Well-conducted systematic reviews can provide a foundation upon which to base
      educational curricula, practice guidelines and healthcare policy. We aim to
      provide an overview of important methodological issues that need to be addressed
      during the five phases of performing a systematic review. 1. The specific
      problems to be addressed by the systematic review need to be formulated as clear,
      unambiguous and structured question/s. 2. Literature from multiple resources
      should be searched to avoid publication biases, as positive outcomes are more
      likely to be published than null/negative results. 3. The quality of selected
      articles should be assessed using a checklist, while the reliability of graders,
      as well as the quality of the checklist, needs to be established a priori. 4.
      Statistical heterogeneity needs to be assessed to determine if a meta-analysis is
      appropriate to pool the data. If not, a narrative synthesis of the
      evidence/overall findings needs to be performed within a clinical context. 

PMID- 25846030
TI  - Binding proteins enhance specific uptake rate by increasing the substrate
      transporter encounter rate.
AB  - Microorganisms rely on binding-protein assisted, active transport systems to
      scavenge for scarce nutrients. Several advantages of using binding proteins in
      such uptake systems have been proposed. However, a systematic, rigorous and
      quantitative analysis of the function of binding proteins is lacking. By
      combining knowledge of selection pressure and physiochemical constraints, we
      derive kinetic, thermodynamic, and stoichiometric properties of binding-protein
      dependent transport systems that enable a maximal import activity per amount of
      transporter. Under the hypothesis that this maximal specific activity of the
      transport complex is the selection objective, binding protein concentrations
      should exceed the concentration of both the scarce nutrient and the transporter.
      This increases the encounter rate of transporter with loaded binding protein at
      low substrate concentrations, thereby enhancing the affinity and specific uptake
      rate. These predictions are experimentally testable, and a number of observations
      confirm them. 

PMID- 25846032
TI  - C-reactive protein and model for end-stage liver disease score: Have we found the
      fifth element?

PMID- 25846033
TI  - Intrafollicular iron and ferritin in women with ovarian endometriomas.
AB  - OBJECTIVE: To evaluate whether iron contained in ovarian endometriomas can
      diffuse through the cyst wall and negatively affect ovarian function. DESIGN:
      Prospective case series. SETTING: Infertility unit in an academic setting.
      POPULATION: Thirty-nine infertile women with unilateral endometriomas who
      underwent in vitro fertilization. METHODS: Iron and ferritin assessments in pools
      of follicular fluids obtained from affected and contralateral intact gonads. MAIN
      OUTCOME MEASURES: Iron and ferritin concentrations. RESULTS: Follicular fluid
      iron content did not differ between the two gonads. The median [interquartile
      range (IQR)] follicular concentrations in the affected and unaffected ovaries
      were 59 (IQR 44-74) and 59 (IQR 47-73) MUg/dL, respectively (p = 0.77).
      Conversely, ferritin concentration was significantly higher in affected gonads.
      The median (IQR) concentrations of ferritin in the affected and unaffected
      ovaries were 57 (IQR 31-146) and 33 (IQR 23-67) MUg/mL, respectively (p = 0.026).
      When considering together the 78 studied ovaries, no significant correlations
      emerged between follicular iron and ferritin and variables reflecting ovarian
      responsiveness and oocyte developmental competence. CONCLUSIONS: Iron may diffuse
      from ovarian endometriomas into the adjacent ovarian tissue. However, this
      phenomenon does not appear to markedly affect ovarian function. Some effective
      biological mechanisms such as ferritin storage may effectively sequester free
      iron, so limiting its detrimental effects.

PMID- 25846034
TI  - Introduction: free speech and the regulation of reproductive health.

PMID- 25846031
TI  - Switch from oral pramipexole or ropinirole to rotigotine transdermal system in
      advanced Parkinson's disease: an open-label study.
AB  - OBJECTIVE: Investigate safety, feasibility and efficacy of switching therapy in
      patients with advanced-stage Parkinson's disease (PD) inadequately controlled
      with pramipexole (<= 3.5 mg/day) or ropinirole (<= 14 mg/day) to rotigotine
      transdermal system (<= 14 mg/24 h; dose adjustments <= 16 mg/24 h permitted).
      METHODS: PD0009 (ClinicalTrials.gov: NCT01711866) was an open-label study in
      patients with advanced-stage PD receiving levodopa, and experiencing sleep
      disturbance or early-morning motor impairment. Pramipexole/ropinirole was
      switched to equivalent dose rotigotine overnight or in two stages. During the 4
      week treatment period rotigotine dose adjustments were permitted (up to 16 mg/24
      h). Primary variable: Clinical Global Impressions (CGI) item 4: side effects
      (assessing safety) at end of treatment. RESULTS: 79/87 (91%) patients completed
      the study; 2 (2%) withdrew due to adverse events (AEs). Most (84; 97%) had CGI
      item 4 score < 3 indicating switch did not interfere with functioning; three
      experienced drug-related AEs interfering with functioning (score = 3). 62%
      patients improved on Patient Global Impression of Change, assessing
      effectiveness. AEs occurring >= 5%: application site pruritus (10%), application
      site erythema (7%), dizziness (7%), dyskinesia (7%), erythema (6%), pruritus
      (6%). Unified Parkinson's Disease Rating Scale II and III, Parkinson's Disease
      Sleep Scale-2 and Pittsburgh Sleep Quality Index were unchanged. Numerical
      improvements in 'off' time, awakenings and nocturias were observed. CONCLUSIONS:
      Switch from pramipexole or ropinirole to rotigotine (up to 14 mg/24 h) was
      feasible and possibly associated with some benefit.

PMID- 25846035
TI  - Abortion and compelled physician speech.
AB  - Informed consent mandates for abortion providers may infringe the First
      Amendment's freedom of speech. On the other hand, they may reinforce the
      physician's duty to obtain informed consent. Courts can promote both doctrines by
      ensuring that compelled physician speech pertains to medical facts about abortion
      rather than abortion ideology and that compelled speech is truthful and not
      misleading. 

PMID- 25846036
TI  - The first amendment and physician speech in reproductive decision making.
AB  - Courts are divided as to whether abortion informed consent mandates violate the
      First Amendment. This article argues that given the doctor's and patient's unique
      expertise, the patient's strong interests in autonomous decision making, and the
      fact that these laws regulate speech, rather than conduct, heighted or strict
      scrutiny should apply to such mandates. 

PMID- 25846037
TI  - A matter of context: Casey and the constitutionality of compelled physician
      speech.
AB  - Under the Supreme Court's compelled speech cases, the context of government
      mandated disclosures determines the standard of review. Pursuant to Casey,
      Zauderer, and Whalen, compelled disclosures in the medical context, such as
      speech-and-display ultrasound laws, are subject to - and survive - a form of
      rational basis scrutiny. 

PMID- 25846038
TI  - Informed decision making and abortion: crisis pregnancy centers, informed
      consent, and the first amendment.
AB  - Shifting laws and regulations increasingly displace the centrality of women's
      health concerns in the provision of abortion services. This is exemplified by the
      growing presence of deceptive Crisis Pregnancy Centers alongside new informed
      consent laws designed to dissuade women from seeking abortions. Litigation on
      informed consent is further complicated in the clinical context due to the
      increased mobilization of facts - such as the gestational age or sonogram of the
      fetus - delivered with the intent to dissuade women from accessing abortion. In
      other words, factual information utilized for ideological purpose. To preserve a
      woman's autonomy and decision-making capacity, there must be a concerted effort
      on the part of legislators and courts to place a woman's health at the center of
      abortion law and policy. 

PMID- 25846039
TI  - Casey meets the crisis pregnancy centers.
AB  - Recent cases have found factual disclosure requirements to be constitutional when
      imposed on abortion providers but unconstitutional when imposed on crisis
      pregnancy centers. This paper argues that the outcomes in both kinds of cases can
      be explained by courts' perception of abortion as an ideological, political, or
      moral act rather than as health care. 

PMID- 25846040
TI  - When states regulate emergency contraceptives like abortion, what should guide
      disclosure?
AB  - State laws dictating "informed consent" about surgical and chemical abortions
      sometimes ensnare emergency contraceptives (EC), as the science surrounding EC
      shows. Courts evaluating mandated disclosures gravitate to professional norms
      rather than the information most women would value: basic factual information
      about EC so that they can decide for themselves whether to use these drugs. 

PMID- 25846041
TI  - Are all abortions equal? Should there be exceptions to the criminalization of
      abortion for rape and incest?
AB  - Politics, public discourse, and legislation restricting abortion has settled on a
      moderate orthodoxy: restrict abortion, but leave exceptions for pregnancies that
      result from rape and incest. I challenge that consensus and suggest it may be
      much harder to defend than those who support the compromise think. From both Pro
      Life and Pro-Choice perspectives, there are good reasons to treat all abortions
      as equal. 

PMID- 25846042
TI  - Acoustic separation and biomedical research: lessons from Indian regulation of
      compensation for research injury.
AB  - In early 2013, the Indian government introduced new rules governing the conduct
      of clinical trials involving human participants. Among other provisions, the law
      requires that sponsors of research compensate participants who are injured during
      the course of their research participation. This article examines the effects of
      India's compensation law and the efforts that policymakers in India have made to
      tailor the law since its passage. I use the legal concept of acoustic separation
      as a framework to explain and justify the approach that India has taken in
      refining its regulation of research related injuries. I conclude that India's
      example may provide useful lessons for research sponsors and lawmakers in other
      regulatory states seeking to promote a well-regulated biomedical research
      industry. 

PMID- 25846043
TI  - Detecting, preventing, and responding to "fraudsters" in internet research:
      ethics and tradeoffs.
AB  - Internet-based health research is increasing, and often offers financial
      incentives but fraudulent behavior by participants can result. Specifically,
      eligible or ineligible individuals may enter the study multiple times and receive
      undeserved financial compensation. We review past experiences and approaches to
      this problem and propose several new strategies. Researchers can detect and
      prevent Internet research fraud in four broad ways: (1) through the
      questionnaire/instrument (e.g., including certain questions in survey; and
      software for administering survey); (2) through participants' non-questionnaire
      data and seeking external validation (e.g., checking data for same email
      addresses, usernames, passwords, and/or fake addresses or phone numbers; (3)
      through computer information, (e.g., IP addresses and cookies), and 4) through
      study design (e.g., avoid lump sum compensation and interviewing participants).
      These approaches each have pros and cons, and raise ethical, legal, and
      logistical questions, given that ethical tensions can emerge between preserving
      the integrity of research vs. protecting the privacy and confidentiality of study
      respondents. While past discussions concerning the ethics of online research have
      tended to focus on the participants' ability to trust the researchers, needs now
      arise to examine researchers' abilities to trust the participants. This analysis
      has several critical implications for future practice, policy, and research. 

PMID- 25846044
TI  - On the justifiability of ACMG recommendations for reporting of incidental
      findings in clinical exome and genome sequencing.
AB  - This paper examines three possible justifications for original ACMG
      recommendations to return incidental findings from whole exome or genome
      sequencing independent of patient preferences. The first two potential
      justifications, based on a patient's authentic values, then on harms to others,
      are founding lacking as a basis of justification for these recommendations. The
      third, grounded in analogous professional practices, might serve as a potential
      justification if several controversies can be avoided. However, given the nature
      of these controversies and the need to instill public trust in this newly
      emerging science, the paper finds that updated ACMG recommendations that
      recognize opt-out rights on behalf of patients is the most prudent, and
      justifiable, approach. 

PMID- 25846045
TI  - Global justice and health systems research in low- and middle-income countries.
AB  - Scholarship focusing on how international research can contribute to justice in
      global health has primarily explored requirements for the conduct of clinical
      trials. Yet health systems research in low- and middle-income countries (LMICs)
      has increasingly been identified as vital to the reduction of health disparities
      between and within countries. This paper expands an existing ethical framework
      based on the health capability paradigm - research for health justice - to
      externally-funded health systems research in LMICs. It argues that a specific
      form of health systems research in LMICs is required if the enterprise is to
      advance global health equity. "Research for health justice" requirements for
      priority setting, research capacity strengthening, and post-study benefits in
      health systems research are derived in light of the field's distinctive
      characteristics. Specific obligations are established for external research
      actors, including governments, funders, sponsors, and investigators. How these
      framework requirements differ from those for international clinical research is
      discussed. 

PMID- 25846046
TI  - The patient as consumer: empowerment or commodification? Currents in contemporary
      bioethics.
AB  - Discussions surrounding patient engagement and empowerment often use the terms
      "patient" and "consumer" interchangeably. But do the two terms hold the same
      meaning, or is a "patient" a passive actor in the health care arena and a
      "consumer" an informed, rational decision-maker? Has there been a shift in our
      usage of the two terms that aligns with the increasing commercialization of
      health care in the U.S. or has the patient/consumer dynamic always been a part of
      the buying and selling of health care in the American system? Recent discussions
      of the issue exist in the popular press and in social media forums such as
      TEDMED, but few direct analyses of the ethical, legal, and policy ramifications
      of this possible shift in terminology are available in the academic literature.
      This paper analyzes our usage of the terms and any recent changes in the dynamic
      and discusses the ethical, legal, and policy implications of this simple
      terminology for the physicianpatient relationship. 

PMID- 25846049
TI  - The Hippo pathway transcriptional co-activator, YAP, confers resistance to
      cisplatin in human oral squamous cell carcinoma.
AB  - Cisplatin (CDDP) is widely used to treat oral squamous cell carcinoma (OSCC),
      however, many patients exhibit acquired drug resistance. Yes-associated protein
      (YAP) is a transcriptional co-activator of the Hippo pathway that regulates organ
      size and promotes cell proliferation. YAP overexpression correlates with
      epithelial-mesenchymal transition and nodal metastasis, resulting in anti-tubulin
      drug resistance. Whether YAP overexpression is the cause of CDDP resistance in
      cancer cells is unclear, therefore, we investigated the correlation between YAP
      expression and CDDP sensitivity. We established three CDDP-resistant cell lines
      (OSC-19-R, SCCKN-R and HSC-3-R) from the OSCC parental cell lines. We also
      examined the expression levels of ATP7B, GST-pi and ERCC1, which are strongly
      associated with CDDP resistance, and Hippo pathway-related proteins by western
      blotting. Using immunocytochemistry, we examined the cellular localization of
      YAP. Additionally, following knockdown of YAP using short interfering RNAs
      (siRNAs), we analyzed changes in sensitivity to CDDP. Compared with parental OSC
      19 cells, OSC-19-R cells were obviously larger. Expression levels of YAP were not
      significantly different between OSC-19 and OSC-19-R. However, expression levels
      of phosphorylated YAP in OSC-19-R were decreased. We observed translocation of
      YAP from the cytoplasm to the nucleus in OSC-19-R cells. Knockdown of YAP using
      siRNAs revealed that sensitivity to CDDP was significantly increased.
      Translocation of YAP correlated with the acquisition of CDDP resistance. YAP
      could be a new therapeutic target for the treatment of patients with cancer that
      are resistant to CDDP. 

PMID- 25846048
TI  - Lanthionine ketimine ester provides benefit in a mouse model of multiple
      sclerosis.
AB  - Lanthionine ketimine (LK) is a natural sulfur amino acid metabolite which binds
      to collapsin response mediator protein-2 (CRMP2), an abundant brain protein that
      interacts with multiple partners to regulate microtubule dynamics, neurite growth
      and retraction, axonal transport, and neurotransmitter release. LK ethyl-ester
      (LKE) is a cell-permeable synthetic derivative that promotes neurogenesis,
      suppresses nitric oxide production from microglia, and reduces neurotoxicity of
      microglia-conditioned medium. These properties led us to test the effects of LKE
      in experimental autoimmune encephalomyelitis (EAE), a commonly used mouse model
      of multiple sclerosis. Female C57Bl/6 mice were immunized with myelin
      oligodendrocyte glycoprotein peptide 35-55 to develop a chronic disease. LKE was
      provided in the chow at 100 ppm, ad libitum beginning when the mice reached
      moderate clinical signs. Over the following 4 weeks the LKE-treated mice showed a
      significant reduction in clinical signs compared to vehicle-treated mice. LKE
      dose dependently reduced IFNgamma production from splenic T cells, but had no
      effect on IL-17 production suggesting protective effects were mediated within the
      CNS. Electron microscopy revealed that, compared to sham mice, EAE mice had
      significant neurodegeneration in both the optic nerve and spinal cord, which was
      reduced in the LKE-treated mice. In contrast only minimal disruption of myelin
      was observed at this time point. In the optic nerve, measurements of axon caliber
      and myelin thickness showed little changes between sham and EAE mice, however,
      treatment with LKE increased the percentage of axons with thicker myelin and with
      larger axon calibers. In the spinal cord, only smaller effects of LKE on myelin
      thickness were observed. The effects of LKE were associated with a reduced
      relative level of phosphorylated CRMP2 to CRMP2. Together, these results
      demonstrate that LKE reduces neurodegeneration in a chronic EAE model of MS,
      which could have translation potential for treatment of progressive forms of MS.

PMID- 25846050
TI  - Palmitic acid, verified by lipid profiling using secondary ion mass spectrometry,
      demonstrates anti-multiple myeloma activity.
AB  - Recent studies indicate that lipid metabolic changes affect the survival of
      multiple myeloma (MM) cells. Time-of-flight secondary ion mass spectrometry (TOF
      SIMS), an imaging mass spectrometry technique, is used to visualize the
      subcellular distribution of biomolecules including lipids. We therefore applied
      this method to human clinical specimens to analyze the membrane fatty acid
      composition and determine candidate molecules for MM therapies. We isolated MM
      cells and normal plasma cells (PCs) from bone marrow aspirates of MM patients and
      healthy volunteers, respectively, and these separated cells were analyzed by TOF
      SIMS. Multiple ions including fatty acids were detected and their ion counts were
      estimated. In MM cells, the mean intensity of palmitic acid was significantly
      lower than the mean intensity in PCs. In a cell death assay, palmitic acid
      reduced U266 cell viability dose-dependently at doses between 50 and 1000 MUM.
      The percentage of apoptotic cells increased from 24h after palmitic acid
      administration. In contrast, palmitic acid had no effect on the viability of
      normal peripheral blood mononuclear cells (PBMCs). The results of this study
      indicated that palmitic acid is a potential candidate for novel therapeutic
      agents that specifically attack MM cells.

PMID- 25846051
TI  - Can Nonurgent Emergency Department Care Costs be Reduced? Empirical Evidence from
      a U.S. Nationally Representative Sample.
AB  - BACKGROUND: A well-functioning primary care system has the capacity to provide
      effective care for patients to avoid nonurgent emergency department (ED) use and
      related costs. OBJECTIVE: This study examined how patients' perceived deficiency
      in ambulatory care is associated with nonurgent ED care costs nationwide.
      METHODS: This retrospective cohort study used data from the 2010-2011 Medical
      Expenditure Panel Survey. This study chose usual source of care, convenience of
      needed medical care, and patient evaluation of care quality as the main
      independent variables. The marginal effect following a multivariate logit model
      was employed to analyze the urgent vs. nonurgent ED care costs in 2011, after
      controlling for covariates in 2010. The endogeneity was accounted for by the time
      lag effect and controlling for education levels. Sample weights and variance were
      adjusted with the survey procedures to make results nationally representative.
      RESULTS: Patient-perceived poor and intermediate levels of primary care quality
      had higher odds of nonurgent ED care costs (odds ratio [OR] = 2.22, p = 0.035,
      and OR = 2.05, p = 0.011, respectively) compared to high-quality care, with a
      marginal effect (at means) of 13.0% and 11.5% higher predicted probability of
      nonurgent ED care costs. Costs related to these ambulatory care quality
      deficiencies amounted to $229 million for private plans (95% confidence interval
      [CI] $100 million-$358 million), $58.5 million for public plans (95% CI $33.9
      million-$83.1 million), and an overall of $379 million (95% CI $229 million-$529
      million) nationally. CONCLUSIONS: These findings highlight the improvement in
      ambulatory care quality as the potential target area to effectively reduce
      nonurgent ED care costs.

PMID- 25846052
TI  - Neuronal Organization of the Brain in the Adult Amphioxus (Branchiostoma
      lanceolatum): A Study With Acetylated Tubulin Immunohistochemistry.
AB  - Amphioxus (Cephalochordata) belongs to the most basal extant chordates, and
      knowledge of their brain organization appears to be key to deciphering the early
      stages of evolution of vertebrate brains. Most comprehensive studies of the
      organization of the central nervous system of adult amphioxus have investigated
      the spinal cord. Some brain populations have been characterized via
      neurochemistry and electron microscopy, and the overall cytoarchitecture of the
      brain was studied by Ekhart et al. (2003; J. Comp. Neurol. 466:319-330) with
      general staining methods and retrograde transport from the spinal cord. Here, the
      cytoarchitecture of the brain of adult amphioxus Branchiostoma lanceolatum was
      reinvestigated by using acetylated tubulin immunohistochemistry, which
      specifically stains neurons and fibers, in combination with some ancillary
      methods. This method allowed reproducible staining and mapping of types of
      neuron, mostly in brain regions caudal to the entrance level of nerve 2, and its
      comparison with spinal cord populations. The brain populations studied and
      discussed in detail were the Retzius bipolar cells, lamellate cells, Joseph
      cells, various types of translumenal cells, somatic motoneurons, Rohde nucleus
      cells, small ventral multipolar neurons, and Edinger cells. These observations
      expand our knowledge of the distribution of cell types and provide additional
      data on the number of cells and the axonal tracts and commissural regions of the
      adult amphioxus brain. The results of this comprehensive study provide a
      framework for comparison of complex adult populations with the early brain
      neuronal populations revealed in developmental studies of the amphioxus.

PMID- 25846053
TI  - Effectiveness of a balance-training program provided by qualified care workers
      for community-based older adults: A preliminary study.
AB  - The purpose of this study was to determine the effectiveness of a balance
      training program provided by qualified care workers (QCWs) to community-based
      older adults attending day centers. Weekly balance training was conducted by QCWs
      working at day centers over a 6-month period. Fall risk factors, fear of falling,
      and physical function were compared between balance-training (n = 22) and control
      (n = 23) groups at baseline and after 6 months of intervention. Physical function
      assessments included the following: one-leg standing test, chair-standing test
      (CST), timed up-and-go test (TUGT), and a lower-extremity muscle strength test
      (LEST). Participants who underwent balance training significantly improved in the
      CST and LEST, and had reduced fear and risk of falling compared with the control
      group (p < 0.05). In the balance-training group, the TUGT was significantly
      better at 6 months than at baseline (p < 0.05). A balance-training program for
      community-dwelling older adults can be effectively implemented by QCWs.

PMID- 25846054
TI  - Effects of garlic oil, nitrate, saponin and their combinations supplemented to
      different substrates on in vitro fermentation, ruminal methanogenesis, and
      abundance and diversity of microbial populations.
AB  - AIMS: To investigate the effect of garlic oil (G), nitrate (N), saponin (S) and
      their combinations supplemented to different forage to concentrate substrates on
      methanogenesis, fermentation, diversity and abundances of bacteria and Archaea in
      vitro. METHODS AND RESULTS: The study was conducted in an 8 * 2 factorial design
      with eight treatments and two substrates using mixed ruminal batch cultures
      obtained. Quillaja S (0.6 g l(-1) ), N (5 mmol l(-1) ) and G (0.27 g l(-1) ) were
      used separately or in binary and tertiary combinations. The two substrates
      contained grass hay and a dairy concentrate mixture at a 70 : 30 (high-forage
      substrate) ratio or a 30 : 70 (high-concentrate substrate) ratio. Ruminal
      fermentation and cellulolytic bacterial populations were affected by interaction
      between substrate and anti-methanogenic compounds. The inhibitor combinations
      decreased the methane production additively regardless of substrate. For the high
      concentrate substrate, S decreased methane production to a greater extent, so did
      G and N individually for the high-forage substrate. Feed degradability and total
      volatile fatty acid (VFA) concentrations were not decreased by any of the
      treatments. Fibre degradability was actually improved by N+S for the high-forage
      substrate. VFA concentrations and profiles were affected differently by different
      anti-methanogenic inhibitors and their combinations. All treatments inhibited the
      growth of Archaea, but the effect on Fibrobacter succinogenes, Ruminococcus albus
      and Ruminococcus flavefaciens varied. CONCLUSIONS: The results suggest that
      substrate influences the efficacy of these inhibitors when they are used
      separately, but in combinations, they can lower methanogenesis additively without
      much influence from the substrate. SIGNIFICANCE AND IMPACT OF THE STUDY: The
      presented research provided evidence that binary and tertiary combination of
      garlic oil, nitrate and saponin can lower the methane production additively
      without adversely impacting rumen fermentation and degradability, and forage to
      concentrate ratio does not change the above effects. These anti-methanogenic
      inhibitors in combination may have practical application to mitigate methane
      emission from ruminants.

PMID- 25846056
TI  - Haploinsufficiency of ANO6, NELL2 and DBX2 in a boy with intellectual disability
      and growth delay.
AB  - We report on a 10-year-old-boy presenting with moderate intellectual disability
      (ID), impaired motor skills, hypotonia, growth delay, minor anomalies, misaligned
      teeth, pectus excavatum, small hands and feet, widely spaced nipples, and a 1.13
      Mb de novo deletion on HSA12q12 (chr12:44,830,147-45,964,945 bp, hg19), deleting
      ANO6, NELL2, and DBX2 and the pseudogenes PLEKHA8P1 and RACGAP1P. We suggest DBX2
      and NELL2 as disease-causing genes and their haploinsufficiency to be involved in
      the psychomotor delay in the patient. DBX2 encodes a homeobox protein, highly
      expressed during neuronal development and regulating differentiation of
      interneurons in brain and spinal cord. NELL2 is expressed in most of the central
      and peripheral nervous system, with highest expression in hippocampus and
      cerebellum, maximizing during neuronal differentiation. The deletion in our
      patient is the smallest in HSA12q12 reported to date, and it is included in the
      deletion carried by four previously reported patients. The clinical presentation
      of these patients points to the recurrence of the following manifestation,
      possibly delineating a 12q12 deletion syndrome phenotype: moderate to severe
      developmental/intellectual delay, hypotonia, postnatal growth retardation,
      skeletal and dental anomalies, minor facial anomalies including strabismus, down
      slanting palpebral fissures, and large/low-set ears.

PMID- 25846055
TI  - Oral administration of non-absorbable delayed release 6-mercaptopurine is locally
      active in the gut, exerts a systemic immune effect and alleviates Crohn's disease
      with low rate of side effects: results of double blind Phase II clinical trial.
AB  - Therapy for Crohn's disease (CD) with thiopurines is limited by systemic side
      effects. A novel formulation of fixed-dose, delayed-release 6-mercaptopurine (DR
      6MP) was developed, with local effect on the gut immune system and minimal
      absorption. The aim of this study was to evaluate the safety and efficacy of DR
      6MP in patients with moderately severe CD compared to systemically delivered 6
      mercaptopurine (Purinethol). Seventy CD patients were enrolled into a 12-week,
      double-blind controlled trial. The primary end-point was the percentage of
      subjects with clinical remission [Crohn's Disease Activity Index (CDAI) < 150] or
      clinical response (100-point CDAI reduction). Twenty-six (56.5%) and 13 (54.2%)
      subjects from the DR-6MP and Purinethol cohorts, respectively, completed the
      study. DR-6MP had similar efficacy to Purinethol following 12 weeks of treatment.
      However, the time to maximal clinical response was 8 weeks for DR-6MP versus 12
      weeks for Purinethol. A higher proportion of patients on DR-6MP showed clinical
      remission at week 8. A greater improvement in Inflammatory Bowel Disease
      Questionnaire (IBDQ) score was noted in the DR-6MP group. DR-6MP led to a
      decrease of CD62(+) expression on T cells, implying a reduction of lymphocyte
      adhesion to site of inflammation. DR-6MP was safer than Purinethol, with
      significantly fewer adverse events (AEs). There was no evidence of drug-induced
      leucopenia in the DR-6MP group; the proportion of subjects who developed
      hepatotoxicity was lower for the DR-6MP. Non-absorbable DR-6MP is safe and
      biologically active in the gut. It is clinically effective, exerting a systemic
      immune response with low systemic bioavailability and a low incidence of side
      effects. 

PMID- 25846057
TI  - Effective climate change refugia for coral reefs.

PMID- 25846058
TI  - Ratiometric fluorescence detection of tyrosinase activity and dopamine using
      thiolate-protected gold nanoclusters.
AB  - In this work, a sensitive and selective ratiometric fluorescence sensing platform
      was built for the detection of tyrosinase (TYR) activity and dopamine (DA) using
      glutathione (GSH) protected gold nanoclusters (Au NCs) as probes. Upon excitation
      at 350 nm, Au NCs displayed an intense red emission, which could be effectively
      quenched by quinones. TYR, a typical polyphenol oxidase, can catalyze the
      oxidization of DA to o-quinone and therefore quenched the fluorescence of Au NCs.
      Moreover, the reaction of TYR and DA gave rise to an emission band at 400 nm,
      which increased in a TYR/DA-concentration-dependent manner. The ratiometric
      signal variations were utilized for facile, sensitive, and selective detection of
      TYR activity and DA. A linear range was obtained from 0.006-3.6 unit mL(-1) of
      TYR activity, while the linear range for detection of DA was 1.0 nM to 1.0 mM.
      Additionally, it constructed a useful platform for TYR inhibitor screening in
      biomedical research. 

PMID- 25846059
TI  - Carotenoid-enriched transgenic corn delivers bioavailable carotenoids to poultry
      and protects them against coccidiosis.
AB  - Carotenoids are health-promoting organic molecules that act as antioxidants and
      essential nutrients. We show that chickens raised on a diet enriched with an
      engineered corn variety containing very high levels of four key carotenoids (beta
      carotene, lycopene, zeaxanthin and lutein) are healthy and accumulate more
      bioavailable carotenoids in peripheral tissues, muscle, skin and fat, and more
      retinol in the liver, than birds fed on standard corn diets (including commercial
      corn supplemented with colour additives). Birds were challenged with the
      protozoan parasite Eimeria tenella and those on the high-carotenoid diet grew
      normally, suffered only mild disease symptoms (diarrhoea, footpad dermatitis and
      digital ulcers) and had lower faecal oocyst counts than birds on the control
      diet. Our results demonstrate that carotenoid-rich corn maintains poultry health
      and increases the nutritional value of poultry products without the use of feed
      additives. 

PMID- 25846060
TI  - Sulfakinin is an important regulator of digestive processes in the migratory
      locust, Locusta migratoria.
AB  - Sulfakinin (SK) is a sulfated insect neuropeptide that is best known for its
      function as a satiety factor. It displays structural and functional similarities
      with the vertebrate peptides gastrin and cholecystokinin. Peptidomic studies in
      multiple insects, crustaceans and arachnids have revealed the widespread
      occurrence of SK in the arthropod phylum. Multiple studies in hemi- and
      holometabolous insects revealed the pleiotropic nature of this neuropeptide: in
      addition to its activity as a satiety factor, SK was also reported to affect
      muscle contraction, digestive enzyme release, odor preference, aggression and
      metabolism. However, the main site of action seems to be the digestive system of
      insects. In this study, we have investigated whether SK can intervene in the
      control of nutrient uptake and digestion in the migratory locust (Locusta
      migratoria). We provide evidence that sulfakinin reduces food uptake in this
      species. Furthermore, we discovered that SK has very pronounced effects on the
      main digestive enzyme secreting parts of the locust gut. It effectively reduced
      digestive enzyme secretion from both the midgut and gastric caeca. SK injection
      also elicited a reduction in absorbance and proteolytic activity of the gastric
      caeca contents. The characteristic sulfation of the tyrosine residue is crucial
      for the observed effects on digestive enzyme secretion. In an attempt to provide
      potential leads for the development of peptidomimetic compounds based on SK, we
      also tested two mimetic analogs of the natural peptide ligand in the digestive
      enzyme secretion assay. These analogs were able to mimic the effect of the
      natural SK, but their effects were milder. The results of this study provide new
      insights into the action of SK on the digestive system in (hemimetabolous)
      insects. 

PMID- 25846061
TI  - Chemical exposures in the workplace and breast cancer risk: A prospective cohort
      study.
AB  - We investigated the relationship between workplace chemical exposures and breast
      cancer risk among women enrolled in the Sister Study, a prospective cohort study
      of US and Puerto Rican women. A total of 47,640 participants reported work
      outside of the home. Workplace exposure to eleven agents (acids, dyes or inks,
      gasoline or other petroleum products, glues or adhesives, lubricating oils,
      metals, paints, pesticides, soldering materials, solvents and stains or
      varnishes) was characterized based on self-reports of frequency and duration of
      use. Approximately 14% of the study population reported exposure to only one
      agent and 11% reported working with two or more of the 11 agents in their
      lifetime. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated
      for each agent, adjusting for established breast cancer risk factors. During
      follow-up, 1,966 cases of breast cancer were reported. Although there were no
      significant associations between ever use of the eleven agents evaluated and
      breast cancer risk, women with cumulative exposure to gasoline or petroleum
      products at or above the highest quartile cutoff had an elevated risk of total
      (HR: 2.3, 95%CI: 1.1-4.9) and invasive (HR: 2.5, 95%CI: 1.1-5.9) breast cancer
      compared with women in the lowest quartile group (ptrend  = 0.03). Workplace
      exposure to soldering materials was associated with an increased risk of
      premenopausal breast cancer (HR = 1.8, 95% CI = 1.1-3.0). Findings support the
      need for further studies to elucidate the role of occupational chemicals in
      breast cancer etiology. 

PMID- 25846062
TI  - Effectiveness of motor practice in lucid dreams: a comparison with physical and
      mental practice.
AB  - Motor practice in lucid dreams is a form of mental rehearsal where the dreamer
      can consciously rehearse motor skills in the dream state while being physically
      asleep. A previous pilot study showed that practice in lucid dreams can improve
      subsequent performance. This study aimed to replicate those findings with a
      different task (finger-tapping) and compare the effectiveness of lucid dream
      practice (LDP) not only to physical but also to mental practice (MP) in
      wakefulness. An online experiment was completed by 68 participants within four
      groups: LDP group, MP group, physical practice (PP) group and control (no
      practice) group. Pre-test was accomplished in the evening, post-test in the next
      morning, while the practice was done during the night. All three practice groups
      significantly improved their performance from pre-test to post-test, but no
      significant improvements were observed for the control group. Subjective sleep
      quality was not affected by night practice. This study thus corroborates the
      previous findings that practice in lucid dreams is effective in improving
      performance. Its effects seem to be similar to actual PP and MP in wakefulness.
      Future studies should establish reliable techniques for lucid dream induction and
      verify the effects of LDP in sleep laboratory conditions. 

PMID- 25846063
TI  - The shape of middle cerebral artery and plaque location: high-resolution MRI
      finding.
AB  - BACKGROUND: The location of plaque may be associated with the vascular geometry.
      AIM: We aimed to examine the relationship between the geometry of middle cerebral
      artery and the plaque location detected by high-resolution magnetic resonance
      imaging. METHODS: Among patients with a single subcortical infarction without a
      significant middle cerebral artery stenosis on magnetic resonance angiography,
      those with a plaque detected from high-resolution magnetic resonance imaging were
      prospectively enrolled. The shape of middle cerebral artery was measured from the
      coronal view, and was classified as straight, U-shaped, inverted U-shaped, and S
      shaped. The location of the plaque was divided into superior and inferior, and
      analyzed according to the shape of middle cerebral artery. RESULTS: Among the 40
      patients, the shape of middle cerebral artery was straight in 7 (17.5%), U-shaped
      in 10 (15.0%), inverted U-shaped in 11 (27.5%), and S-shaped in 12 patients
      (30.0%). The superior plaque was more closely associated with straight (85.7%) or
      U-shaped middle cerebral arteries (90.0%), whereas inverted U-shaped (81.8%) and
      S-shaped middle cerebral arteries (75.0%) were more often associated with
      inferior plaque. The prevalence of symptomatic plaque was higher in superior than
      inferior plaques (70.0% vs. 25.0%, P = 0.004). Multivariate analysis showed that
      straight and U-shaped middle cerebral artery was the only significant factor
      associated with the superior plaque. CONCLUSION: The shape of middle cerebral
      artery may be a factor determining the location of early atherosclerotic plaque.

PMID- 25846064
TI  - Genomic and Proteomic Analysis of Escherichia coli After Spaceflight Reveals
      Changes Involving Metabolic Pathways.
AB  - BACKGROUND AND AIMS: The space environment could have impacts on a variety of
      characteristics of microorganism such as cell metabolism, drug resistance, and
      virulence. However, relevant mechanisms need to be clarified. In the present
      study, the effect of a space environment on Escherichia coli was investigated.
      METHODS: E. coli strains were sent to space for 398 h on the Shenzhou VIII and
      ground simulation was conducted as control. After the flight, a mutant strain LCT
      EC67 was selected for further analysis. RESULTS: Although no changes in
      hemolysis, morphology or antibiotic sensitivity were observed, the mutant strain
      showed elevated carbon source utilization compared with the control group.
      Genomic and proteomic analyses showed that 801 genes were upregulated and 825
      genes were downregulated. In addition, 167 proteins were overexpressed and 92
      proteins were downregulated using a cut-off fold-change value of 1.4 and a p <
      0.05. The changed proteins were associated with metabolic functions such as
      alanine and glutamate metabolism, arginine and proline metabolism, and fatty acid
      and propanoate metabolism. CONCLUSIONS: E. coli showed alterations at gene and
      protein levels mainly regarding biochemical metabolism after spaceflight.

PMID- 25846065
TI  - Antileishmanial pharmacomodulation in 8-nitroquinolin-2(1H)-one series.
AB  - An antileishmanial pharmacomodulation at position 4 of 8-nitroquinolin-2(1H)-one
      was conducted by using the Sonogashira and Suzuki-Miyaura coupling reactions. A
      series of 25 derivatives was tested in vitro on the promastigote stage of
      Leishmania donovani along with an in vitro cytotoxicity evaluation on the human
      HepG2 cell line. Only the derivatives bearing a phenyl moiety at position 4 of
      the quinoline ring displayed interesting biologic profile, when the phenyl moiety
      was substituted at the para position by a Br or Cl atom, or by a CF3 group. Among
      them, molecules 17 and 19 were the most selective and were then tested in vitro
      on the intracellular amastigote stage of both L. donovani and Leishmania
      infantum, in parallel with complementary in vitro cytotoxicity assays on the
      macrophage cell lines THP-1 and J774A.1. Molecule 19 showed no activity on the
      amastigote stages of the parasites and some cytotoxicity on the J774A.1 cell line
      while molecule 17, less cytotoxic than 19, showed anti-amastigote activity in L.
      infantum, being 3 times less active than miltefosine but more active and
      selective than pentamidine. Nevertheless, hit-molecule 17 did not appear as
      selective as the parent compound. 

PMID- 25846066
TI  - Synthesis of a new series of dithiocarbamates with effective human carbonic
      anhydrase inhibitory activity and antiglaucoma action.
AB  - A new series of dithiocarbamates (DTCs) was prepared from primary/secondary
      amines incorporating amino/hydroxyl-alkyl, mono- and bicyclic aliphatic ring
      systems based on the quinuclidine, piperidine, hydroxy-/carboxy-/amino
      substituted piperidine, morpholine and piperazine scaffolds, and carbon
      disulfide. The compounds were investigated for the inhibition of four mammalian
      alpha-carbonic anhydrases (CAs, EC 4.2.1.1) of pharmacologic relevance, that is,
      the human (h) hCA I, II, IX and XII, drug targets for antiglaucoma (hCA II and
      XII) or antitumor (hCA IX/XII) agents. The compounds were moderate or inefficient
      hCA I inhibitors (off-target isoform for both applications), efficiently
      inhibited hCA II, whereas some of them were low nanomolar/subnanomolar hCA IX/XII
      inhibitors. One DTC showed excellent intraocular pressure (IOP) lowering
      properties in an animal model of glaucoma, with a two times better efficiency
      compared to the clinically used sulfonamide dorzolamide. 

PMID- 25846067
TI  - Effect of long-term Helicobacter pylori infection on growth of children: a cohort
      study.
AB  - BACKGROUND: The effects of Helicobacter pylori (H. pylori) infection on growth
      are a controversial issue. We investigated the effects of long-term H. pylori
      infection on height and weight in children. METHODS: A total of 200 children of 7
      18 years old suffering from dyspeptic complaints were classified into two groups:
      H. pylori positive and negative groups, respectively. Whether the infection was
      impoved was followed up while performing urea breath test, and according to
      exposure time to the infection, the children were further divided into group 1
      (<=1.5 months), group 2 (>1.5-<=6 months) and group 3 (>6 months). Antropometric
      measurements were obtained and repeated every six months. RESULTS: Mean growth
      velocity scores in the H. pylori positive and negative groups were 0.49+/-3.85
      [95% confidence interval (CI): -0.21-1.18] and 1.98+/-4.42 (95% CI: 1-2.96),
      respectively. The difference between both groups was statistically significant
      (P=0.012). Mean growth velocity scores in groups 1, 2 and 3 were 0.96+/-3.84,
      0.16+/-4.51 and -0.85+/-3.09, respectively. Mean growth velocity scores of group
      3 were significantly lower than those of groups 0 and 1 (P=0.005 and P=0.041).
      The mean weight scores in group 3 were similar to those in group 2, but the
      scores in group 3 were significantly lower than those in group 1 (-1.75+/-1.05, 
      1.21+/-1.37 and -0.88+/-1.49, respectively). CONCLUSION: As the duration of
      exposure is prolonged in children with H. pylori infection, the negative effect
      of the infection on both height and weight is evident.

PMID- 25846068
TI  - Weaning preterm infants from continuous positive airway pressure: evidence for
      best practice.
AB  - BACKGROUND: Nasal continuous positive airway pressure (NCPAP) is frequently used
      in preterm infants. However, there is no consensus on when and how to wean them
      from NCPAP. DATA SOURCES: Based on recent publications, we have reviewed the
      criteria of readiness-to-wean and factors affecting weaning success. A special
      focus is placed on the methods of weaning from NCPAP in preterm infants. RESULTS:
      Practical points of when and how to wean from NCPAP in preterm infants are
      explained. Preterm infants are ready to be weaned from NCPAP when they are stable
      on a low NCPAP pressure with no (or minimal) oxygen requirement. Methods used to
      wean from NCPAP include: sudden weaning of NCPAP, gradual decrease of NCPAP
      pressure, graded-timeoff NCPAP (cycling), weaning to high or low flow nasal
      cannula, and a combination of these methods. The best strategy for weaning is yet
      to be determined. Cyclingoff NCPAP increases the duration of NCPAP and length of
      hospital stay without beneficial effect on success of weaning. Gradual decrease
      of NCPAP pressure is more physiological and better tolerated than cycling-off
      NCPAP. CONCLUSION: Further studies are needed to reach a consensus regarding the
      optimal timing and the best method for weaning from NCPAP in preterm infants.

PMID- 25846069
TI  - The correlation between plasma cytokine levels in jaundice-free children with
      biliary atresia.
AB  - BACKGROUND: T helper (Th) cell cytokines modulate inflammation and play a role in
      biliary atresia (BA). The aim of the study is a cross-sectional assessment of the
      levels of Th cytokines in the jaundice-free post Kasai procedure patients.
      METHODS: There were 40 jaundice-free patients with BA and 28 normal controls
      enrolled. Patients were divided into 3 groups, including normal liver function,
      impaired liver function, and portal hypertension. Plasma concentration of Th1
      [interferon-gamma (INF-gamma), interleukin (IL)-2], Th2 (IL-4, IL-10), Th3
      [transforming growth factor-beta1 (TGF-beta1)], Th17 (IL-17) cytokines, and
      stromal cell-derived factor-1alpha (SDF-1alpha) were investigated. RESULTS: The
      IFN-gamma level was significantly higher in the BA patients with impaired liver
      function and portal hypertension than controls (P<0.0001 and P<0.0001,
      respectively). There was a significantly increase of TGF-beta1 in all BA groups
      compared with controls (P=0.003). The reduction of SDF-1alpha expression was
      found in BA groups (P<0.0001). IL-10 levels significantly correlated with
      aspartate aminotransferase to platelet ratio index (r=0.496, P=0.001). For the
      cytokine correlations, there were no correlations of Th1, Th2 and Th17 cytokine
      with the other measured cytokines, but TGF-beta1 was negatively correlated with
      SDF-1alpha levels (r=-0.327, P=0.039). CONCLUSIONS: IFN-gamma and IL-10 are
      likely to be involved in the disease progression in BA. Besides, TGF-beta1 is
      found to be a suppression marker associated with SDF-1alpha levels and reduced
      production of TGF-beta1 may be associated with the disease progression.

PMID- 25846070
TI  - Characteristics of respiratory syncytial virus-induced bronchiolitis co-infection
      with Mycoplasma pneumoniae and add-on therapy with montelukast.
AB  - BACKGROUND: The influence of Mycoplasma pneumoniae (MP) infection on
      bronchiolitis remains unclear. Additionally, reports on the efficacies of
      leukotriene receptor antagonists in the treatment of bronchiolitis have been
      inconclusive. METHODS: Children with respiratory syncytial virus (RSV)-induced
      bronchiolitis were divided into two groups: RSV+MP group and RSV group. Each
      group was randomly divided into two subgroups: one received routine and placebo
      treatment, while the other received routine and montelukast treatment for 9
      months. The cumulative numbers of wheezing episodes and recurrent respiratory
      tract infections were recorded. Blood parameters were determined. RESULTS:
      Patients in the RSV+MP group exhibited an older average age, fever, more frequent
      flaky and patchy shadows in chest X-rays, more frequent extrapulmonary
      manifestations, and longer hospital stays compared with patients in the RSV
      group. Additionally, higher baseline blood eosinophil counts, eosinophil cationic
      protein (ECP), total immunoglobulin E (IgE), interleukin (IL)-4, IL-5, IL
      4/interferon-gamma ratios, leukotriene (LT) B4, and LTC4, and lower baseline
      lipoxin A4 (LXA4)/LTB4 ratios were observed in the RSV+MP group compared with the
      RSV group. Montelukast treatment decreased the cumulative numbers of recurrent
      wheezing episodes and recurrent respiratory tract infections at 9 and 12 months.
      This efficacy may be related to the montelukast-induced reductions in peripheral
      eosinophil counts, ECP and total IgE, as well as the montelukast-dependent
      recovery in T helper (Th) 1/Th2 balance and LXA4/LTB4 ratios in children with
      bronchiolitis. CONCLUSIONS: RSV bronchiolitis with MP infection was associated
      with clinical and laboratory features that differed from those of RSV
      bronchiolitis without MP infection. Add-on therapy with montelukast for 9 months
      was beneficial for children with bronchiolitis at 9 and 12 months after the
      initiation of treatment.

PMID- 25846071
TI  - Effects of Bifidobacterium supplementation on intestinal microbiota composition
      and the immune response in healthy infants.
AB  - BACKGROUND: Intestinal microbiotas are thought to be the most important source of
      maturational stimuli to the development of the immune system. However, few
      studies have focused on the development of T helper (Th) 1 immune response and
      antibody response to vaccinations in healthy infants, especially in a large
      cohort. Through this randomized, double-blind control trial, we investigated the
      effects of Bifidobacterium longum BB536 (BB536) supplementation on intestinal
      microbiota composition and the immune response in term infants. METHODS: In
      total, 300 healthy newborns were recruited, randomized and fed formula either
      supplemented with BB536 or with no supplementation. Stool samples were analyzed
      at months 2, 4 and 11. The representative cytokine for Th1 [interferon-gamma (IFN
      gamma)] and Th2 [interleukin-4 (IL-4)] secretion cells were measured using enzyme
      linked immunospot assay at 4 and 7 months of age. The antibody response to
      vaccines was measured at months 7 and 11. RESULTS: A total of 264 infants
      completed the study. The amount of bifidobacteria and the bifidobacteria/
      Enterobacteriaceae ratio (B/E) were significantly higher in the BB536
      supplementation group at months 2 and 4. The number of IFN-gamma secretion cells
      and the ratio of IFN-gamma/IL-4 secretion cells were increased in the BB536
      supplementation group at 7 months. Moreover, the higher value of B/E in the early
      stages seems to be related to the increased Th1 response. No difference was
      observed between groups in the antibody response after vaccination. CONCLUSION:
      BB536 has positive effects on establishing a healthy intestinal microbiota early
      in life, and it also plays an important role in improving the Th1 immune
      response.

PMID- 25846072
TI  - Mean platelet volume in patients with varicocele.

PMID- 25846073
TI  - Mean platelet volume may not be related to the physiopathology of varicocele.

PMID- 25846074
TI  - The Role of C5a Receptor Signaling in Endotoxin-Induced Miscarriage and Preterm
      Birth.
AB  - PROBLEM: Complement factor 5a (C5a), a potent pro-inflammatory mediator of the
      complement system, has been implicated in fetal rejection throughout gestation,
      from miscarriage to preterm birth. This study aimed to investigate the role of
      the principal C5a receptor, C5aR1 (CD88), in both miscarriage and preterm birth,
      in a bacterial endotoxin (lipopolysaccharide; LPS) murine model. METHOD OF STUDY:
      Wild-type and C5ar1 knockout mice were administered LPS at 9.5 or 15.5 days post
      conception to induce miscarriage or preterm birth, respectively. RESULTS: C5ar1
      knockout mice were protected against miscarriage in response to administration of
      LPS in early gestation. However, the absence of C5aR1 had no effect on the rates
      of preterm birth when LPS was administered in late gestation. CONCLUSION: There
      may be a gestational window in which excessive activation of C5a can exert
      deleterious effects in pregnancy. Future strategies targeting the C5a-C5aR1
      signaling axis should be considered to ameliorate miscarriages in patients with
      recurrent pregnancy loss.

PMID- 25846075
TI  - Secreted Frizzled-related protein 3 (sFRP3)-mediated suppression of interleukin-6
      receptor release by A disintegrin and metalloprotease 17 (ADAM17) is abrogated in
      the osteoarthritis-associated rare double variant of sFRP3.
AB  - To avoid malformation and disease, tissue development and homoeostasis are co
      ordinated precisely in time and space. Secreted Frizzled-related protein 3
      (sFRP3), encoded by the Frizzled-related protein gene (FRZB), acts as an
      antagonist of Wnt signalling in bone development by delaying the maturation of
      proliferative chondrocytes into hypertrophic chondrocytes. A disintegrin and
      metalloprotease 17 (ADAM17) is a transmembrane protease that is essential for
      developmental processes and promotes cartilage maturation into bone. sFRP3 is
      chondroprotective and is expressed in chondrocytes of healthy articular
      cartilage. Upon damage to cartilage, sFRP3 is down-regulated. Rare variants of
      sFRP3 are associated with osteoarthritis. The present study demonstrates a novel
      function of sFRP3 in suppression of the enzymatic activity of ADAM17 which
      results in the inhibition of ADAM17-meditated interleukin-6 receptor (IL-6R)
      shedding. By contrast, the rare double variant of sFRP3 failed to suppress
      ADAM17. The shed soluble IL-6R (sIL-6R) is linked to inflammation, cartilage
      degeneration and osteolysis. Accordingly, enhanced activity of ADAM17 in
      cartilage, caused by the expression of the rare double sFRP3 variant, provides an
      explanation for the genetic effect of sFRP3 variants in joint disease. The
      finding that sFRP3 interacts with the ADAM17 substrate IL-6R also suggests a new
      regulatory mechanism by which the substrate is protected against shedding. 

PMID- 25846076
TI  - Multidetector computed tomography pulmonary angiography in childhood acute
      pulmonary embolism.
AB  - Pulmonary embolism is a life-threatening condition affecting people of all ages.
      Multidetector row CT pulmonary angiography has improved the imaging of pulmonary
      embolism in both adults and children and is now regarded as the routine modality
      for detection of pulmonary embolism. Advanced CT pulmonary angiography techniques
      developed in recent years, such as dual-energy CT, have been applied as a one
      stop modality for pulmonary embolism diagnosis in children, as they can
      simultaneously provide anatomical and functional information. We discuss CT
      pulmonary angiography techniques, common and uncommon findings of pulmonary
      embolism in both conventional and dual-energy CT pulmonary angiography, and
      radiation dose considerations. 

PMID- 25846077
TI  - The value of repeat scintigraphy in patients with a high clinical suspicion for
      Meckel diverticulum after a negative or equivocal first Meckel scan.
AB  - BACKGROUND: Technetium (99m)Tc-pertechnetate is the most common and accurate
      noninvasive method of preoperative investigation for Meckel diverticulum. Despite
      introducing various methods to increase the sensitivity of the study, there are
      many case reports of false-negative Meckel scans. A repeat scan is sometimes
      requested in patients with a high suspicion for Meckel diverticulum and negative
      or equivocal first Meckel scan. OBJECTIVES: The purpose of this retrospective
      study is to evaluate the value of repeat scintigraphy for these patients.
      MATERIALS AND METHODS: Seven hundred fifty-three Meckel scans were recorded
      retrospectively. In 33 cases (22 male and 11 female; mean age: 6.8 years), the
      Meckel scintigraphy was repeated either due to a high clinical suspicion of
      Meckel diverticulum and a negative study (n = 21) or due to equivocal findings in
      the first scan (n = 12). The study was interpreted as positive if an abnormal
      focal activity was identified in the abdomen and pelvis during the procedure. The
      results were correlated with pathology and clinical symptoms. RESULTS: Seven out
      of 12 (58%) equivocal studies were positive on the second study. Six of them were
      proven to be positive at operation (confirmed by pathology) while one of them was
      negative on laparoscopy. From 21 negative first scans with a high suspicion for
      Meckel diverticulum, three (14%) were positive on the second study. All three
      were proven to be Meckel diverticulum on pathology. CONCLUSION: Repeat Meckel
      scans in patients with equivocal findings on the first study or a negative result
      with a high clinical suspicion for a Meckel diverticulum are useful especially in
      cases in which the first study had been done without appropriate preparation.

PMID- 25846081
TI  - Novel mutations of low-density lipoprotein receptor gene in China patients with
      familial hypercholesterolemia.
AB  - Familial hypercholesterolaemia (FH) is an autosomal dominant genetic disorder,
      associated with elevated level of serum low-density lipoprotein-cholesterol (LDL
      C), which can lead to premature cardiovascular disease (CVD). Mutations in low
      density lipoprotein receptor (LDLR) and proprotein convertase subtilisin/kexin
      type 9 (PCSK9) have been identified to be the underlying cause of this disease.
      Genetic research of FH has already been extensively studied all over the world.
      However, reports of FH mutations in the Chinese population are still limited. In
      this paper, 20 unrelated FH families were enrolled to detect the candidate gene
      variants in Chinese FH population by DNA direct sequencing. We identified 12 LDLR
      variants in 13 FH probands. Importantly, we first reported two unique mutations
      (c.2000_2000 delG/p.C667LfsX6 and c.605T>C/p.F202S) in LDLR gene. Our discoveries
      expand the spectrum of LDLR mutations and contribute to the genetic diagnosis and
      counseling for FH patients. 

PMID- 25846082
TI  - Dangers of direct-to-consumer advertising exposed again.

PMID- 25846083
TI  - Tackling the cancer epidemic.

PMID- 25846084
TI  - Non-inferiority trials: why oncologists must remain wary.

PMID- 25846085
TI  - Probiotics and cancer: ready for meal time?

PMID- 25846087
TI  - Adjuvant chemotherapy for rectal cancer.

PMID- 25846088
TI  - Adjuvant chemotherapy for rectal cancer.

PMID- 25846089
TI  - Adjuvant chemotherapy for rectal cancer.

PMID- 25846090
TI  - Adjuvant chemotherapy for rectal cancer.

PMID- 25846091
TI  - Adjuvant chemotherapy for rectal cancer - authors' reply.

PMID- 25846092
TI  - Panitumumab for locally advanced head and neck squamous-cell carcinoma.

PMID- 25846093
TI  - Radiotherapy dose and fractionation for stage III NSCLC.

PMID- 25846094
TI  - Correction to Lancet Oncol 2015; 16: 60, 61. Safety and activity of blinatumomab
      for adult patients with relapsed or refractory B-precursor acute lymphoblastic
      leukaemia: a multi-centre, single-arm, phase 2 study.

PMID- 25846095
TI  - Correction to Lancet Oncol 2014; 15: 856. Olaparib maintenance therapy in
      patients with platinum-sensitive relapsed serous ovarian cancer: a preplanned
      retrospective analysis of outcomes by BRCA status in a randomised phase 2 trial.

PMID- 25846096
TI  - Transformation from non-small-cell lung cancer to small-cell lung cancer:
      molecular drivers and cells of origin.
AB  - Lung cancer is the most common cause of cancer deaths worldwide. The two broad
      histological subtypes of lung cancer are small-cell lung cancer (SCLC), which is
      the cause of 15% of cases, and non-small-cell lung cancer (NSCLC), which accounts
      for 85% of cases and includes adenocarcinoma, squamous-cell carcinoma, and large
      cell carcinoma. Although NSCLC and SCLC are commonly thought to be different
      diseases owing to their distinct biology and genomic abnormalities, the idea that
      these malignant disorders might share common cells of origin has been gaining
      support. This idea has been supported by the unexpected findings that a subset of
      NSCLCs with mutated EGFR return as SCLC when resistance to EGFR tyrosine kinase
      inhibitors develops. Additionally, other case reports have described the
      coexistence of NSCLC and SCLC, further challenging the commonly accepted view of
      their distinct lineages. Here, we summarise the published clinical observations
      and biology underlying tumours with combined SCLC and NSCLC histology and cancers
      that transform from adenocarcinoma to SCLC. We also discuss pre-clinical studies
      pointing to common potential cells of origin, and speculate how the distinct
      paths of differentiation are determined by the genomics of each disease. 

PMID- 25846098
TI  - Nail toxicities induced by systemic anticancer treatments.
AB  - Patients treated with systemic anticancer drugs often show changes to their
      nails, which are usually well tolerated and disappear on cessation of treatment.
      However, some nail toxicities can cause pain and functional impairment and thus
      substantially affect a patient's quality of life, especially if they are given
      taxanes or EGFR inhibitors. These nail toxicities can affect both the nail plate
      and bed, and might present as melanonychia, leukonychia, onycholysis,
      onychomadesis, Beau's lines, or onychorrhexis, as frequently noted with
      conventional chemotherapies. Additionally, the periungual area (perionychium) of
      the nail might be affected by paronychia or pyogenic granuloma, especially in
      patients treated with drugs targeting EGFR or MEK. We review the nail changes
      induced by conventional chemotherapies and those associated with the use of
      targeted anticancer drugs and discuss preventive or curative options. 

PMID- 25846097
TI  - Nomograms in oncology: more than meets the eye.
AB  - Nomograms are widely used as prognostic devices in oncology and medicine. With
      the ability to generate an individual probability of a clinical event by
      integrating diverse prognostic and determinant variables, nomograms meet our
      desire for biologically and clinically integrated models and fulfill our drive
      towards personalised medicine. Rapid computation through user-friendly digital
      interfaces, together with increased accuracy, and more easily understood
      prognoses compared with conventional staging, allow for seamless incorporation of
      nomogram-derived prognosis to aid clinical decision making. This has led to the
      appearance of many nomograms on the internet and in medical journals, and an
      increase in nomogram use by patients and physicians alike. However, the
      statistical foundations of nomogram construction, their precise interpretation,
      and evidence supporting their use are generally misunderstood. This issue is
      leading to an under-appreciation of the inherent uncertainties regarding nomogram
      use. We provide a systematic, practical approach to evaluating and comprehending
      nomogram-derived prognoses, with particular emphasis on clarifying common
      misconceptions and highlighting limitations. 

PMID- 25846099
TI  - Accepting risk in the acceleration of drug development for rare cancers.
AB  - Rare cancers collectively contribute a disproportionate fraction of the total
      burden of cancer. The oncology community is increasingly facing small numbers of
      patients with each cancer subtype, requiring cooperation and collaboration to
      complete multicentre trials that advance knowledge and patient care. At the same
      time, new insights into the biology of rare cancers have led to an explosion in
      knowledge and development of targeted agents. These insights and techniques are
      set to revolutionise the care of patients with cancer. However, drug development
      strategies and the availability of new agents for rare cancers are at risk of
      stalling owing to the ever-increasing complexity and costs of clinical trials.
      Finding solutions to these problems is imperative to the future of cancer care.
      We propose that a greater degree of risk sharing is needed than is currently
      accepted to enable the use of new methods with confidence, and to keep pace with
      scientific advancement. 

PMID- 25846100
TI  - Autologous human nasal epithelial cell sheet using temperature-responsive culture
      insert for transplantation after middle ear surgery.
AB  - Postoperative mucosal regeneration of the middle ear cavity and the mastoid
      cavity is of great importance after middle ear surgery. However, the
      epithelialization of the mucosa in the middle ear is retarded because chronic
      inflammation without epithelialization aggravates gas exchange and clinical
      function. These environmental conditions in the middle ear lead to postoperative
      retraction and adhesion of the newly-formed tympanic membrane. Therefore, if the
      mucosa on the exposed middle ear bone surface can be rapidly regenerated after
      surgery, the surgical treatments for cholesteatoma and adhesive middle ear
      disease can potentially be improved. In this study, we successfully generated a
      cell sheet designed for the postoperative treatment of cholesteatoma. We used
      nasal cells to create an artificial middle ear mucosal cell sheet with a three
      dimensional (3D) configuration similar to that of the middle ear mucosa. The
      sheets consisted of multi-layered mucosal epithelia and lower connective tissue
      and were similar to normal middle ear mucosa. This result indicates that tissue
      engineered mucosal cell sheets would be useful to minimize complications after
      surgical operations in the middle ear and future clinical applications are
      expected. Copyright (c) 2015 John Wiley & Sons, Ltd.

PMID- 25846101
TI  - Using travel socialization and underlying motivations to better understand
      motorcycle usage in Taiwan.
AB  - This study introduces self-determination theory (SDT) to refine previous models
      of vehicle usage motivation. We add travel socialization theory regarding
      parental influence on vehicle usage to enhance previous structural models
      describing motorcycle usage behavior. Our newly developed model was empirically
      verified in a sample of 721 motorcycle users in Taiwan. In addition to
      instrumental, symbolic, and affective motivations, perceived parental attitudes
      (PPAs) towards motorcycle riding were found to have a significant effect on
      individuals' motorcycle use habits. Additionally, participants who perceived
      their parents to have more positive attitudes toward motorcycles were found to
      have more experience being chauffeured on motorcycles by their parents. Based on
      these results, we suggest means to confront the challenges brought on by the
      rapid growth of motorcycle usage, especially serious motorcycle traffic
      accidents. These results improve our understanding motorcycle usage in Taiwan and
      can be used by transportation professionals who are seeking solutions to the
      rapid growth of motorcycle usage. 

PMID- 25846102
TI  - An experimental study of factors associated with driver frustration and
      overtaking intentions.
AB  - This study examined directly the impact of various factors associated with
      driving on 'A-class' roads in the United Kingdom (specifically length of platoon,
      proportion of heavy goods vehicles (HGVs), speed and opportunities for
      overtaking) on self-reported frustration and overtaking intentions. The impact of
      situational variables (being under time pressure, and time behind a slower moving
      platoon) were also examined, as was the association between frustration and self
      reported overtaking intentions. 183 members of the public from the areas around
      Perth and Inverness, Scotland took part in the study. Participants viewed
      simulated 'driver's viewpoint' clips representing all the combinations of the
      experimental variables (except time pressure, which was a between-groups
      variable, and time behind platoon, which was examined separately in four specific
      clips). After each clip, participants responded on a paper questionnaire as to
      the level of frustration they would feel for a given clip, and the likelihood
      that at some point during the clip they would have attempted an overtake
      manoeuvre. The findings show that the links between traffic variables such as
      speed and platoon length, and behaviourally-relevant variables such as
      frustration and overtaking intentions, are not simple. Although there are broad
      and predictable effects of speed and platoon length (lower speeds and longer
      platoons leading to greater frustration) these are mediated by other variables,
      and it is not always the case that more frustration leads to more intention to
      overtake. Analysis of driver attitudes identified three clusters (low, medium and
      high risk drivers) and suggests that higher risk drivers' levels of frustration
      are more affected by situational changes than those of lower risk drivers. 

PMID- 25846103
TI  - Attenuation of renovascular hypertension by cyclooxygenase-2 inhibitor partly
      through ANP release.
AB  - Angiotensin II (Ang II) is an important inflammatory mediator. Ang II induces
      cyclooxygenase-2 (COX-2) expression and prostaglandin F2alpha release followed by
      cardiac hypertrophy. Inhibition of COX-2 may modulate high blood pressure but
      controversy still exists. The aim of this study was to determine the role of COX
      2 in the regulation of blood pressure and to define the mechanisms in two kidney
      one-clip hypertensive (2K1C) rats. Chronic treatment with nimesulide or NS-398 (5
      mg/kg/day) for 3 weeks lowered high blood pressure and cardiac hypertrophy with
      decreased expression levels of cardiac hypertrophy markers [atrial natriuretic
      peptide (ANP), brain natriuretic peptide (BNP)], Ang type 1 receptor, urotensin
      II, and urotensin II receptor in 2K1C rats. Plasma level of ANP was markedly
      increased and plasma levels of Ang II and aldosterone were decreased by treatment
      with nimesulide or NS-398. In both in vitro and in vivo experiments, nimesulide
      or NS-398 augmented ANP release in 2K1C rats. The inhibitory effect of NS-398 on
      blood pressure was attenuated by the pretreatment with natriuretic peptide
      receptor-A (NPR-A) antagonist (A71915, 30 MUg/kg/day). These results suggest that
      chronic treatment with nimesulide or NS-398 attenuated hypertension and cardiac
      hypertrophy partly through ANP release in 2K1C rats.

PMID- 25846104
TI  - Fluorogenic sequencing using halogen-fluorescein-labeled nucleotides.
AB  - Fluorogenic sequencing is a sequencing-by-synthesis technology that combines the
      advantages of pyrosequencing and fluorescence detection. With native duplex DNA
      as the major product, we employ polymerase to incorporate the complement- arily
      matched terminal phosphate-labeled fluorogenic nucleotides into the DNA template
      and release halogen-fluorescein as the reporter. This red-emitting fluorophore
      successfully avoids spectral overlap with the autofluorescence background of the
      flow chip. We fully characterized the enzymatic reaction kinetics of the new
      substrates, and performed a 35-base sequencing experiment with 60 reaction
      cycles. Our achievement expands the substrate repertoire for fluorogenic
      sequencing, and extends the spectral range to obtain better signal-to-background
      performance.

PMID- 25846105
TI  - Acceleration of thiol additive-free native chemical ligation by intramolecular S 
      > S acyl transfer.
AB  - Peptide-mercaptopropionylcysteine (MPA-Cys) thioesters show a surprisingly high
      reactivity in native chemical ligation (NCL) and allow thiol-additive free
      reactions. This facilitates sequential NCL reactions and ligation-desulfurization
      reactions in one-pot formats. The synthetic utility is demonstrated by the
      synthesis of a SH3 domain. 

PMID- 25846106
TI  - Establishment and characterization of a novel VEGF-producing HHV-8-unrelated PEL
      like lymphoma cell line, OGU1.
AB  - Primary effusion lymphoma (PEL) is a rare B-cell lymphoma subtype that is
      characterized by lymphomatous effusion without the presence of masses, and it
      typically occurs in human immunodeficiency virus (HIV)-infected individuals.
      Lymphoma cells are universally positive for human herpesvirus 8 (HHV-8).
      Recently, a cavity-based effusion lymphoma that is similar to PEL without HHV-8
      infection, called HHV-8-unrelated PEL-like lymphoma, has been reported in non-HIV
      infected individuals. However, the pathophysiology of this lymphoma is largely
      undefined. We established a novel B-cell line OGU1 derived from a patient with
      HHV-8-unrelated PEL-like lymphoma. Notably, OGU1 cells produced vascular
      endothelial growth factor (VEGF) and expressed VEGF receptor 1, whose inhibitors
      retarded cell growth. Because VEGF acts as a vascular permeability and growth
      factor, it could play a role, at least in part, in the pathogenesis of this
      unique lymphoma. Thus, the OGU1 cell line is useful for the investigation of HHV
      8-unrelated PEL-like lymphoma. 

PMID- 25846107
TI  - Membrane-intercalating conjugated oligoelectrolytes: impact on bioelectrochemical
      systems.
AB  - Conjugated oligoelectrolytes (COEs), molecules that are defined by a pi
      delocalized backbone and terminal ionic pendant groups, have been previously
      demonstrated to effectively reduce charge-injection/extraction barriers at
      metal/organic interfaces in thin-film organic-electronic devices. Recent studies
      demonstrate a spontaneous affinity of certain COEs to intercalate into, and align
      within, lipid bilayers in an ordered orientation, thereby allowing modification
      of membrane properties and the functions of microbes in bioelectrochemical and
      photosynthetic systems. Several reports have provided evidence of enhanced
      current generation and bioproduction. Mechanistic approaches suggest that COEs
      influence microbial extracellular electron transport to abiotic electrode
      surfaces via more than one proposed pathway, including direct electron transfer
      and meditated electron transfer. Molecular dynamics simulations as a function of
      molecular structure suggest that insertion of cationic COEs results in membrane
      thinning as the lipid phosphate head groups are drawn toward the center of the
      bilayer. Since variations in molecular structures, especially the length of the
      conjugated backbone, distribution of ionic groups, and hydrophobic substitutions,
      show an effect on their antimicrobial properties, preferential cell localization,
      and microbial selection, it is promising to further design novel membrane
      intercalating molecules based on COEs for practical applications, including
      energy generation, environmental remediation, and antimicrobial treatment. 

PMID- 25846113
TI  - Correction and optimization of a T2-based approach to map blood oxygenation in
      small cerebral veins.
AB  - PURPOSE: Cerebral venous blood oxygenation (Yv ) is an important biomarker in
      brain physiology and function. The present study proposes a procedure to provide
      a quantitative map of the brain's intravascular Yv. THEORY AND METHODS: The
      method is based on a pulse sequence, T2 -Relaxation-Under-Phase-Contrast (TRU-PC)
      MRI, with postprocessing approaches to correct eddy-current effects. A complete
      scan protocol consists of four TRU-PC scans sensitized to large and small vessels
      with anterior-posterior and foot-head flow-encoding directions, and the data are
      analyzed conjunctively. Eddy-current correction was performed by fitting the
      tissue phase to a hyperplane, and then subtracting the eddy-current phase from
      the measured vessel phase. The reproducibility of the Yv-maps was examined in
      five participants. Sensitivity of the Yv map to a caffeine challenge was studied
      in another five participants. RESULTS: Removal of eddy-current induced artifact
      allowed for the correction of T2 measurements, as demonstrated in vivo and with
      simulation. A Yv-map depicting all vessels in the slice can be obtained with the
      proposed protocol. Test-retest variability of the Yv -map was 3.7 +/- 1.2%. Yv
      reduction can be reliably detected (P < 0.001) following the caffeine ingestion.
      CONCLUSION: With the proposed TRU-PC protocol and eddy-current correction
      procedure, an accurate, vessel-specific Yv map of the human brain can be
      obtained.

PMID- 25846115
TI  - Ups and Downs in Auditory Development: Preschoolers' Sensitivity to Pitch Contour
      and Timbre.
AB  - Much research has explored developing sound representations in language, but less
      work addresses developing representations of other sound patterns. This study
      examined preschool children's musical representations using two different tasks:
      discrimination and sound-picture association. Melodic contour--a musically
      relevant property--and instrumental timbre, which is (arguably) less musically
      relevant, were tested. In Experiment 1, children failed to associate cartoon
      characters to melodies with maximally different pitch contours, with no advantage
      for melody preexposure. Experiment 2 also used different-contour melodies and
      found good discrimination, whereas association was at chance. Experiment 3
      replicated Experiment 2, but with a large timbre change instead of a contour
      change. Here, discrimination and association were both excellent. Preschool-aged
      children may have stronger or more durable representations of timbre than
      contour, particularly in more difficult tasks. Reasons for weaker association of
      contour than timbre information are discussed, along with implications for
      auditory development.

PMID- 25846114
TI  - Dietary nitrate improves sprint performance and cognitive function during
      prolonged intermittent exercise.
AB  - It is possible that dietary nitrate (NO3 (-)) supplementation may improve both
      physical and cognitive performance via its influence on blood flow and cellular
      energetics. PURPOSE: To investigate the effects of dietary NO3 (-)
      supplementation on exercise performance and cognitive function during a prolonged
      intermittent sprint test (IST) protocol, which was designed to reflect typical
      work patterns during team sports. METHODS: In a double-blind randomised crossover
      study, 16 male team-sport players received NO3 (-)-rich (BR; 140 mL day(-1); 12.8
      mmol of NO3 (-)), and NO3 (-)-depleted (PL; 140 mL day(-1); 0.08 mmol NO3 (-))
      beetroot juice for 7 days. On day 7 of supplementation, subjects completed the
      IST (two 40-min "halves" of repeated 2-min blocks consisting of a 6-s "all-out"
      sprint, 100-s active recovery and 20 s of rest), on a cycle ergometer during
      which cognitive tasks were simultaneously performed. RESULTS: Total work done
      during the sprints of the IST was greater in BR (123 +/- 19 kJ) compared to PL
      (119 +/- 17 kJ; P < 0.05). Reaction time of response to the cognitive tasks in
      the second half of the IST was improved in BR compared to PL (BR first half: 820
      +/- 96 vs. second half: 817 +/- 86 ms; PL first half: 824 +/- 114 vs. second
      half: 847 +/- 118 ms; P < 0.05). There was no difference in response accuracy.
      CONCLUSIONS: These findings suggest that dietary NO3 (-) enhances repeated sprint
      performance and may attenuate the decline in cognitive function (and specifically
      reaction time) that may occur during prolonged intermittent exercise.

PMID- 25846116
TI  - miR-34c plays a role of tumor suppressor in HEC-1-B cells by targeting E2F3
      protein.
AB  - Endometrial carcinoma (EC) is a common malignancy of the female genital tract
      with a poor prognosis. It has been reported that miR-34c is significantly reduced
      in EC, but research concerning its function in EC is rare. In the present study,
      the expression of miR-34c was upregulated in the EC cell line, HEC-1-B, by
      transfecting the cells with hsa-miR-34c-5p mimics. Then, after determining the
      transfection efficiency by RT-qPCR, we analyzed the effects of miR-34c on the HEC
      1-B cells. We found that overexpression of miR-34c significantly inhibited cell
      proliferation, colony formation, migration and invasion and induced cell cycle
      arrest and apoptosis. Finally, western blot analysis demonstrated that the
      expression of E2F3 was reduced after upregulation of the expression of miR-34c in
      the HEC-1-B cells, and the effects of miR-34c are likely associated with the
      reduction in E2F3 protein. In conclusion, our study demonstrated that miR-34c
      plays a role of tumor suppressor in HEC-1-B cells, and E2F3 protein may be a
      target of miR-34c. 

PMID- 25846117
TI  - Laryngocele: an unusual presentation.

PMID- 25846118
TI  - Solitary neurofibroma originating from the posterior nasal septum: Transnasal
      endoscopic resection.
AB  - INTRODUCTION: The head and neck region is one of the locations of neurogenic
      tumors such as neurofibroma. Although mostly associated with neurofibromatosis,
      it can be solitary. The present study reports a very rare case of solitary
      neurofibroma originating from the posterior nasal septum. CASE PRESENTATION: A 48
      year-old female presented with tumor in the right nasal cavity. The tumor,
      originating in the posterior nasal septum, extended to the posterior sinuses and
      nasopharynx. Following endoscopic and radiological assessment, the tumor was
      resected by transnasal endoscopic surgery. Histological examination showed the
      tumor to be a neurofibroma. At 14months' follow-up, there was no recurrence.
      DISCUSSION AND CONCLUSIONS: However rare, solitary neurofibroma must be
      considered in the differential diagnosis of unilateral benign tumor involving
      nasal and paranasal sinuses. A transnasal endoscopic approach should be
      considered for treatment.

PMID- 25846119
TI  - Giant tumour of the parotid gland.

PMID- 25846120
TI  - Value and limits of non-robotic transoral oropharyngectomy for local control of
      T1-2 invasive squamous cell carcinoma of the tonsillar fossa.
AB  - BACKGROUND: An analysis of the value and limits of non-robotic transoral
      oropharyngectomy for local control of T1-2 squamous cell carcinoma of the
      tonsillar fossa. METHODS: A retrospective series of 111 T1 and 133 T2 (N0: 129;
      N1: 52; N2: 53; N3: 10). Induction chemotherapy and postoperative radiation
      therapy were used in 63.5% and 29.5% of cases, respectively. Actuarial analysis
      of local failure, impact of various variables upon local failure and consequences
      of local failure upon other oncological events and survival are documented.
      RESULTS: The 5-year actuarial local failure estimate was 10.4% and 14.2% for T1
      and T2 tumors, respectively. The 5-year actuarial local failure estimate was
      significantly reduced when resection margins were safe or yielded dysplasia
      (P=0.008) and when induction chemotherapy achieved complete histologic regression
      (P=0.013). Salvage treatment achieved a 97.2% and 93.2% overall local control
      rate in T1 and T2 tumors, respectively. The 5-year actuarial nodal failure
      estimate was 35.1% in patients with local failure versus 10.8% without
      (P=0.0001). The 5-year actuarial metachronous second primary estimate was 7% in
      patients with local failure versus 33.2% without (P=0.016). The impact of local
      failure on survival (5-year actuarial survival estimate: 67.3% without and 46.4%
      with local failure) was not significant. CONCLUSION: In T1-2 squamous cell
      carcinoma of the tonsillar fossa, non-robotic transoral oropharyngectomy appeared
      to be highly effective in terms of local control. The high incidence of head and
      neck metachronous second primaries further advocates the use of this treatment
      option in order to reserve radiation therapy to such cases.

PMID- 25846121
TI  - Gorillas with white sclera: A naturally occurring variation in a morphological
      trait linked to social cognitive functions.
AB  - Human eye morphology is considered unique among the primates in that humans
      possess larger width/height ratios (WHR), expose a greater amount of visible
      sclera (SSI; width of exposed eyeball/width of visible iris), and critically,
      have a white sclera due to a lack of pigmentation. White sclera in humans
      amplifies gaze direction, whereas the all-dark eyes of apes are hypothesized to
      conceal gaze from others. This study examines WHR and SSI in humans (N = 13) and
      gorillas (N = 85) engaged in direct and averted gazes and introduces a
      qualitative assessment of sclera color to evaluate variations in sclera
      pigmentation. The results confirm previous findings that humans possess a larger
      WHR than gorillas but indicate that humans and gorillas display similar amounts
      of visible sclera. Additionally, 72% (N = 124) of gorilla eyes in this sample
      deviated from the assumed all-dark eye condition. This questions whether gaze
      camouflage is the primary function of darkened sclera in non-human primates or
      whether other functional roles can be ascribed to the sclera, light or dark. We
      argue that white sclera evolved to amplify direct gazes in humans, which would
      have played a significant role in the development of ostensive communication,
      which is communication that both shows something and shows the intention to show
      something. We conclude that the horizontal elongation of the human eye, rather
      than sclera color, more reliably distinguishes human from great ape eyes,
      represented here by gorillas.

PMID- 25846122
TI  - Meat intake, cooking methods, dietary carcinogens, and colorectal cancer risk:
      findings from the Colorectal Cancer Family Registry.
AB  - Diets high in red meat and processed meats are established colorectal cancer
      (CRC) risk factors. However, it is still not well understood what explains this
      association. We conducted comprehensive analyses of CRC risk and red meat and
      poultry intakes, taking into account cooking methods, level of doneness,
      estimated intakes of heterocyclic amines (HCAs) that accumulate during meat
      cooking, tumor location, and tumor mismatch repair proficiency (MMR) status. We
      analyzed food frequency and portion size data including a meat cooking module for
      3364 CRC cases, 1806 unaffected siblings, 136 unaffected spouses, and 1620
      unaffected population-based controls, recruited into the CRC Family Registry.
      Odds ratios (OR) and 95% confidence intervals (CI) for nutrient density variables
      were estimated using generalized estimating equations. We found no evidence of an
      association between total nonprocessed red meat or total processed meat and CRC
      risk. Our main finding was a positive association with CRC for pan-fried
      beefsteak (P(trend) < 0.001), which was stronger among MMR deficient cases
      (heterogeneity P = 0.059). Other worth noting associations, of borderline
      statistical significance after multiple testing correction, were a positive
      association between diets high in oven-broiled short ribs or spareribs and CRC
      risk (P(trend) = 0.002), which was also stronger among MMR-deficient cases, and
      an inverse association with grilled hamburgers (P(trend) = 0.002). Our results
      support the role of specific meat types and cooking practices as possible sources
      of human carcinogens relevant for CRC risk.

PMID- 25846123
TI  - Abstinence and relapse among smokers who use varenicline in a quit attempt-a
      pooled analysis of randomized controlled trials.
AB  - BACKGROUND AND AIMS: Varenicline increases the likelihood of long-term abstinence
      following a quit attempt. It has been suggested that (1) part of its benefit
      arises from 'recruiting into abstinence' smokers who are not able to stop on the
      target quit date and (2) there may be a higher rate of relapse after treatment.
      This study addressed these issues. METHODS: Meta-analyses of data from randomized
      controlled trials (RCTs) of varenicline identified from the 2012 Cochrane review
      of nicotine receptor partial agonists for smoking cessation were used to compare
      the abstinence and relapse patterns on active drug and placebo. Studies of
      varenicline compared with placebo in adult daily smokers with longest follow-up
      at either 6 or 12 months and with at least three follow-ups in the first month
      were included. Biochemically verified abstinence rates at each of six follow-up
      time-points (2, 3, 4, 12, 24 and 52 weeks) were pooled for studies reporting
      point prevalence abstinence. Biochemically verified abstinence rates at three
      follow-up time-periods (9-12 weeks, 9-24 weeks and 9-52 weeks) were pooled for
      studies reporting continuous abstinence. Random effects meta-analysis was used to
      estimate pooled proportions with 95% confidence intervals. RESULTS: Nineteen RCTs
      were included. In varenicline-treated participants, point-prevalence abstinence
      increased by 22 percentage points from week 2 [32%: 95% confidence interval (CI)
      = 25-40%] to week 12 (54%: 95% CI = 48-61%). The increase was 8 percentage points
      in the placebo group: 16% (95% CI = 11-21%) to 24% (95% CI = 17-33%). In
      varenicline-treated participants the relapse from weeks 9-12 to week 52 was 55%:
      49% abstinent in weeks 9-12 (95% CI = 45-53%) versus 22% at week 52 (95% CI = 19
      25%). In placebo-treated participants it was 53%: 17% (95% CI = 13-25%) in weeks
      9-12 versus 8% (95% CI = 6-12%) at week 52. CONCLUSIONS: Varenicline recruits
      smokers into abstinence following the target quit date to a greater extent than
      placebo. Relapse rates from end of treatment to 52 weeks are similar in
      varenicline- and placebo-treated smokers.

PMID- 25846124
TI  - Deletion analysis of Streptococcus pneumoniae late competence genes distinguishes
      virulence determinants that are dependent or independent of competence induction.
AB  - The competence regulon of Streptococcus pneumoniae (pneumococcus) is crucial for
      genetic transformation. During competence development, the alternative sigma
      factor ComX is activated, which in turn, initiates transcription of 80 'late'
      competence genes. Interestingly, only 16 late genes are essential for genetic
      transformation. We hypothesized that these late genes that are dispensable for
      competence are beneficial to pneumococcal fitness during infection. These late
      genes were systematically deleted, and the resulting mutants were examined for
      their fitness during mouse models of bacteremia and acute pneumonia. Among these,
      14 late genes were important for fitness in mice. Significantly, deletion of some
      late genes attenuated pneumococcal fitness to the same level in both wild-type
      and ComX-null genetic backgrounds, suggesting that the constitutive baseline
      expression of these genes was important for bacterial fitness. In contrast, some
      mutants were attenuated only in the wild-type genetic background but not in the
      ComX-null background, suggesting that specific expression of these genes during
      competence state contributed to pneumococcal fitness. Increased virulence during
      competence state was partially caused by the induction of allolytic enzymes that
      enhanced pneumolysin release. These results distinguish the role of basal
      expression versus competence induction in virulence functions encoded by ComX
      regulated late competence genes. 

PMID- 25846125
TI  - Does dose matter in reducing gestational weight gain in exercise interventions? A
      systematic review of literature.
AB  - OBJECTIVES: The purpose of this review was to examine the relationship between
      exercise dose and reductions in weight gain during pregnancy in exercise
      interventions. DESIGN: Systematic literature review. METHODS: Four electronic
      research databases (PubMed, Web of Science, CINAHL, and Academic Search Premiere)
      were used to identify exercise interventions conducted with pregnant women.
      Eligible articles must have satisfied the following criteria: inclusion of a
      control condition, exercise as a major intervention component, weight gain
      measured and reported for each experimental condition, description of exercise
      dose (frequency, intensity and duration), and utilized an adequate number of
      control conditions to assess independent effects of exercise on weight gain.
      RESULTS: The literature search identified 4837 articles. Of these, 174 abstracts
      were screened and 21 intervention studies (18 exercise-only, 3 exercise/diet)
      were eligible for review. Only 38% of the interventions achieved statistically
      significant reductions in gestational weight gain. Successful interventions
      possessed higher adherence and lower attrition rates and were predominantly
      conducted among normal weight populations. No clear patterns or consistencies of
      exercise dose and reductions in weight gain were evident. CONCLUSIONS: An
      exercise dose associated with reductions in weight gain was unquantifiable among
      these interventions. Adherence and retention rates were strong contributors to
      the success of exercise interventions on gestational weight gain. It is strongly
      suggested that future researchers investigate methods to increase adherence and
      compliance, especially among overweight and obese women, and utilize objective
      measurement tools to accurately evaluate exercise dose performed by the
      participants and the impact on body composition and weight gain.

PMID- 25846126
TI  - More children more active: Tailored playgrounds positively affect physical
      activity levels amongst youth.
AB  - OBJECTIVES: Overall physical activity (PA) of children is low, and the physical
      inactivity problem is highest in deprived neighborhoods. The overall goal of the
      Richard Krajicek Foundation is to provide children in deprived neighborhoods with
      safe public playgrounds that stimulate daily PA. This study investigates whether
      Krajicek playgrounds are associated with higher usage and intensity of PA
      compared to control playgrounds during playground use amongst children. DESIGN:
      Cross-sectional observational study. METHODS: Ten Krajicek and ten control
      playgrounds in The Netherlands were matched for neighborhood and playground
      characteristics. Usage and intensity of PA at the playgrounds were measured using
      direct observation (SOPLAY). Trained observers collected PA data after-school
      time on weekdays and weekend days. Multilevel regression analyses were performed
      to analyze the difference in usage and intensity of PA between control and
      Krajicek playgrounds. RESULTS: Krajicek playgrounds were significantly less often
      empty compared to control playgrounds (12% vs. 29%). In addition, there was a
      statistically significant difference in the number of boys observed on the
      Krajicek playgrounds (14 vs. 9, OR 1.8). Across all categories differences in
      playground PA were found with an average of 13% of the children on Krajicek
      playgrounds engaged in moderate-to-vigorous physical activity (MVPA) compared to
      10% on control playgrounds. Energy-expenditure (EE) per child was higher on
      Krajicek playgrounds across all groups (B.006). CONCLUSIONS: Krajicek playgrounds
      are positively associated with higher usage and PA intensity compared to control
      playgrounds. Our results indicate that Krajicek playgrounds can benefit PA of
      children living in deprived neighborhoods during playground play.

PMID- 25846128
TI  - Syntheses, structures, and magnetic properties of three new cyano-bridged
      complexes based on the [Mn(CN)6](3-) building block.
AB  - With three pentadentate macrocyclic ligands, three new [Mn(CN)6](3-) based
      complexes, [Mn(L(N3O2))(H2O)]2[Mn(CN)6](ClO4).3H2O (1), {[Mn(L(N5))]3[Mn(CN)6]2}n
      (2) and {[Mn(L(N5Me))]3[Mn(CN)6]2}n.10nH2O (3) (L(N3O2) = 2,13-dimethyl-6,9-dioxa
      3,12,18-triazabicyclo[12.3.1]octadeca-1(18),2,12,14,16-pentaene, L(N5) = 2,13
      dimethyl-3,6,9,12,18-pentaazabicyclo-[12.3.1]octadeca-1(18),2,12,14,16-pentaene,
      L(N5Me) = 2,6-bis[1-(2-(N-methylamino)ethylimino)ethyl]-pyridine), have been
      synthesized and characterized structurally and magnetically. The structure of 1
      was found to be a linear Mn2(II)Mn(III) trinuclear cluster with two Mn(II)
      capping groups and one Mn(III) ion connected via two trans-cyano groups. In
      contrast, compounds 2 and a3 re cyano-bridged 2D networks. Magnetic investigation
      revealed antiferromagnetic coupling between the Mn(III) and Mn(II) ions via the
      bridging cyanide groups. Complex 1 showed paramagnetic behavior down to 2.0 K
      with no sign of SMM behavior. The magnetic coupling constant of J = -1.63 cm(-1)
      with the Hamiltonian H = -2J(S(Mn(III)).SMn(II)1 + SMn(III).S(Mn(II)2)) was
      obtained from the fitting of the magnetic susceptibility. For 2 and 3,
      ferrimagnetic ordering was observed with magnetic phase transition temperatures
      (Tc) being 7.5 K and 7.0 K, respectively. These compounds are rare examples of a
      small number of [Mn(CN)6](3-) based magnetic materials.

PMID- 25846129
TI  - Total tract nutrient digestion and milk fatty acid profile of dairy cows fed
      diets containing different levels of whole raw soya beans.
AB  - Whole oilseeds such as soya beans have been utilized in dairy rations to supply
      additional fat and protein. However, antinutritional components contained in soya
      beans, such as trypsin inhibitors and haemagglutinins (lectins) may alter
      digestibility of nutrients and consequently affect animal performance. The
      objective of the present experiment was to quantify the effect of different
      levels of whole raw soya beans in diets of dairy cows on nutrient intake, total
      tract digestion, nutrient balances and milk yield and composition. Sixteen mid to
      late-lactation cows (228 +/- 20 days in milk; mean +/- SD) were used in four
      replicated 4 * 4 Latin square design experiment with 21-d periods. Cows were
      assigned to each square according to milk yield and DIM. The animals were
      randomly allocated to treatments: control (without soya beans addition; CO), WS9,
      WS18 and WS27, with addition of 9%, 18% and 27% of whole raw soya bean in diet on
      a dry matter (DM) basis respectively. All diets contained identical forage and
      concentrate components and consisted of maize silage and concentrate based on
      ground corn and soya beans at a ratio of 60:40. There were no differences in OM,
      CP, NDF and NEL intakes (kg/day and MJ/day) among the treatments (p > 0.05).
      However, DM and NFC intakes were negatively affected (p = 0.04 and p < 0.01,
      respectively) and ether extract (EE) intake was positively affected (p < 0.01).
      Total tract digestion increased linearly with whole raw soya beans for EE (p <
      0.01) and NDF (p = 0.01). The excretion (kg/day) of digested soya beans grains
      increased linearly according to addition of whole raw soya beans. However, the
      nutritive characteristics of excreted grains were not altered. Milk (kg), milk
      lactose (kg) and protein (kg) yield decreased linearly (p < 0.01, p < 0.01 and p
      = 0.04, respectively) milk fat content (%) increased linearly (p < 0.01) with
      whole raw soya beans inclusion. Increasing addition of whole raw soya beans
      affected milk fatty acid profile with a linear decrease of cis-9-trans 11CLA and
      total saturated FA; and linear increase of total unsaturated and C18:3 FA. Energy
      balance was positively affected (p = 0.03) by whole raw soya beans as well as
      efficiency of NEL milk/DE intake (p = 0.02). Nitrogen balance and microbial
      protein synthesis were not affected by whole raw soya beans. Increasing doses of
      whole raw soya beans decreased dry matter intake and milk yield, however, led to
      an increase of unsaturated acids in milk and higher milk fat concentration.

PMID- 25846127
TI  - A Low Protein Binding Cationic Poly(2-oxazoline) as Non-Viral Vector.
AB  - Developing safe and efficient non-viral gene delivery systems remains a major
      challenge. We present a new cationic poly(2-oxazoline) (CPOx) block copolymer for
      gene therapy that was synthesized by sequential polymerization of non-ionic 2
      methyl-2-oxazoline and a new 2-oxazoline monomer, 2-(N-methyl, N-Boc-amino)
      methyl-2-oxazoline, followed by deprotection of the pendant secondary amine
      groups. Upon mixing with plasmid DNA (pDNA), CPOx forms small (diameter ~80 nm)
      and narrowly dispersed polyplexes (PDI <0.2), which are stable upon dilution in
      saline and against thermal challenge. These polyplexes exhibited low plasma
      protein binding and very low cytotoxicity in vitro compared to the polyplexes of
      pDNA and poly(ethylene glycol)-b-poly(L-lysine) (PEG-b-PLL). CPOx/pDNA polyplexes
      at N/P = 5 bound considerably less plasma protein compared to polyplexes of PEG-b
      PLL at the same N/P ratio. This is a unique aspect of the developed polyplexes
      emphasizing their potential for systemic delivery in vivo. The transfection
      efficiency of the polyplexes in B16 murine melanoma cells was low after 4 h, but
      increased significantly for 10 h exposure time, indicative of slow
      internalization of polyplexes. Addition of Pluronic P85 boosted the transfection
      using CPOx/pDNA polyplexes considerably. The low protein binding of CPOx/pDNA
      polyplexes is particularly interesting for the future development of targeted
      gene delivery. 

PMID- 25846130
TI  - Appraising the methodological quality of cadaveric studies: validation of the
      QUACS scale.
AB  - Although systematic reviews are conducted in the field of anatomical research, no
      instruments exist for the assessment of study quality. Thus, our objective was to
      develop a valid tool that reliably assesses the methodological quality of
      observational cadaveric studies. The QUACS scale (QUality Appraisal for Cadaveric
      Studies) was developed using an expert consensus process. It consists of a 13
      item checklist addressing the design, conduct and report of cadaveric dissection
      studies. To evaluate inter-rater reliability, a blinded investigator obtained an
      initial pool of 120 observational cadaveric studies. Sixty-eight of them were
      selected randomly according to sample size calculations. Three independent
      researchers rated each publication by means of the QUACS scale. The reliability
      of the total score was estimated using the intraclass correlation coefficient
      (ICC). To assess agreement among individual items, margin-free kappa values were
      calculated. For construct validity, two experts (an anatomist and an experienced
      physician) categorized the quality of 15 randomly selected studies as 'excellent'
      (4 points), 'moderate to good' (3 points), poor to moderate' (2 points) or 'poor'
      (1 point). Kendall's tau rank correlation was used to compare the expert ratings
      with the scores on the QUACS scale. An evaluation of feasibility was carried out
      during the reliability analysis. All three raters recorded the duration of
      quality appraisal for each article. Means were used to describe average time
      exposure. The ICC for the total score was 0.87 (95% confidence interval: 0.82
      0.92; P < 0.0001). For individual items, margin-free kappa values ranged between
      0.56 and 0.96 with an agreement of 69-97% among the three raters. Kendall's tau B
      coefficient of the association between expert ratings and the results obtained
      with the QUACS scale was 0.69 (P < 0.01). Required rating time per article was
      5.4 +/- 1.6 min. The QUACS scale is highly reliable and exhibits strong construct
      validity. Thus, it can confidently be applied in assessing the methodological
      quality of observational dissection studies. 

PMID- 25846131
TI  - Characterization of a 520 kb deletion on chromosome 15q26.1 including ST8SIA2 in
      a patient with behavioral disturbance, autism spectrum disorder, and epilepsy:
      additional information.

PMID- 25846133
TI  - Stereogenic alpha-carbons determine the shape and topology of [13]
      macrodilactones.
AB  - The synthesis and characterization of new [13]-macrodilactones substituted at
      stereogenic centers alpha- to the carbonyl are reported. When one center is
      substituted, it directs the topology of the macrocycle; when two centers are
      substituted, both the shape and the topology are influenced. The findings
      indicate that the number and configuration of alpha-centers fine-tune macrocyclic
      structure. 

PMID- 25846132
TI  - Spinal muscular atrophy functional composite score: A functional measure in
      spinal muscular atrophy.
AB  - INTRODUCTION: With clinical trials underway, our objective was to construct a
      composite score of global function that could discriminate among people with
      spinal muscular atrophy (SMA). METHODS: Data were collected from 126 participants
      with SMA types 2 and 3. Scores from the Hammersmith Functional Motor Scale
      Expanded and Upper Limb Module were expressed as a percentage of the maximum
      score and 6-minute walk test as percent of predicted normal distance. A principal
      component analysis was performed on the correlation matrix for the 3 percentage
      scores. RESULTS: The first principal component yielded a composite score with
      approximately equal weighting of the 3 components and accounted for 82% of the
      total variability. The SMA functional composite score, an unweighted average of
      the 3 individual percentage scores, correlated almost perfectly with the first
      principal component. CONCLUSIONS: This combination of measures broadens the
      spectrum of ability that can be quantified in type 2 and 3 SMA patients.

PMID- 25846134
TI  - Acid sensitivity of the spinal dorsal root ganglia C-fiber nociceptors
      innervating the guinea pig esophagus.
AB  - BACKGROUND: Gastroesophageal reflux can cause high acidity in the esophagus and
      trigger heartburn and pain. However, because of the esophageal mucosal barrier,
      the acidity at the nerve terminals of pain-mediating C-fibers in esophageal
      mucosa is predicted to be substantially lower. We hypothesized that the
      esophageal dorsal root ganglia (DRG) C-fibers are activated by mild acid
      (compared to acidic reflux), and express receptors and ion channels highly
      sensitive to acid. METHODS: Extracellular single unit recordings of activity
      originating in esophageal DRG C-fiber nerve terminals were performed in the
      innervated esophagus preparation ex vivo. Acid was delivered in a manner that
      bypassed the esophageal mucosal barrier. The expression of mRNA for selected
      receptors in esophagus-specific DRG neurons was evaluated using single cell RT
      PCR. KEY RESULTS: Mild acid (pH = 6.5-5.5) activated esophageal DRG C-fibers in a
      pH-dependent manner. The response to mild acid at pH = 6 was not affected by the
      TRPV1 selective antagonist iodo-resiniferatoxin. The majority (70-95%) of
      esophageal DRG C-fiber neurons (TRPV1-positive) expressed mRNA for acid sensing
      ion channels (ASIC1a, ASIC1b, ASIC2b, and/or ASIC3), two-pore-domain (K2P)
      potassium channel TASK1, and the proton-sensing G-protein coupled receptor OGR1.
      Other evaluated targets (PKD2L1, TRPV4, TASK3, TALK1, G2A, GPR4, and TDAG8) were
      expressed rarely. CONCLUSIONS & INFERENCES: Guinea pig esophageal DRG C-fibers
      are activated by mild acid via a TRPV1-independent mechanism, and express mRNA
      for several receptors and ion channels highly sensitive to acid. The high acid
      sensitivity of esophageal C-fibers may contribute to heartburn and pain in
      conditions of reduced mucosal barrier function.

PMID- 25846136
TI  - Differential dynamics of RAS isoforms in GDP- and GTP-bound states.
AB  - RAS subfamily proteins regulates cell growth promoting signaling processes by
      cycling between active (GTP-bound) and inactive (GDP-bound) states. Different RAS
      isoforms, though structurally similar, exhibit functional specificity and are
      associated with different types of cancers and developmental disorders.
      Understanding the dynamical differences between the isoforms is crucial for the
      design of inhibitors that can selectively target a particular malfunctioning
      isoform. In this study, we provide a comprehensive comparison of the dynamics of
      all the three RAS isoforms (HRAS, KRAS, and NRAS) using extensive molecular
      dynamics simulations in both the GDP- (total of 3.06 MUs) and GTP-bound (total of
      2.4 MUs) states. We observed significant differences in the dynamics of the
      isoforms, which rather interestingly, varied depending on the type of the
      nucleotide bound and the simulation temperature. Both SwitchI (Residues 25-40)
      and SwitchII (Residues 59-75) differ significantly in their flexibility in the
      three isoforms. Furthermore, Principal Component Analysis showed that there are
      differences in the conformational space sampled by the GTP-bound RAS isoforms. We
      also identified a previously unreported pocket, which opens transiently during MD
      simulations, and can be targeted to regulate nucleotide exchange reaction or
      possibly interfere with membrane localization. Further, we present the first
      simulation study showing GDP destabilization in the wild-type RAS protein. The
      destabilization of GDP/GTP occurred only in 1/50 simulations, emphasizing the
      need of guanine nucleotide exchange factors (GEFs) to accelerate such an
      extremely unfavorable process. This observation along with the other results
      presented in this article further support our previously hypothesized mechanism
      of GEF-assisted nucleotide exchange.

PMID- 25846135
TI  - The role of pyruvate hub enzymes in supplying carbon precursors for fatty acid
      synthesis in photosynthetic microalgae.
AB  - Photosynthetic microalgae are currently the focus of basic and applied research
      due to an ever-growing interest in renewable energy resources. This review
      discusses the role of carbon-unit supply for the production of acetyl-CoA, a
      direct precursor of fatty acid biosynthesis and the primary building block of the
      growing acyl chains for the purpose of triacylglycerol (TAG) production in
      photosynthetic microalgae under stressful conditions. It underscores the
      importance of intraplastidic acetyl-CoA generation for storage lipid
      accumulation. The main focus is placed on two enzymatic steps linking the central
      carbon metabolism and fatty acid synthesis, namely the reactions catalyzed by the
      plastidic isoform of pyruvate kinase and the chloroplastic pyruvate dehydrogenase
      complex. Alternative routes for plastidic acetyl-CoA synthesis are also reviewed.
      A separate section is devoted to recent advances in functional genomics studies
      related to fatty acid and TAG biosynthesis.

PMID- 25846137
TI  - Small-Molecule Transport by CarO, an Abundant Eight-Stranded beta-Barrel Outer
      Membrane Protein from Acinetobacter baumannii.
AB  - Outer membrane (OM) beta-barrel proteins composed of 12-18 beta-strands mediate
      cellular entry of small molecules in Gram-negative bacteria. Small OM proteins
      with barrels of 10 strands or less are not known to transport small molecules.
      CarO (carbapenem-associated outer membrane protein) from Acinetobacter baumannii
      is a small OM protein that has been implicated in the uptake of ornithine and
      carbapenem antibiotics. Here we report crystal structures of three isoforms of
      CarO. The structures are very similar and show a monomeric eight-stranded barrel
      lacking an open channel. CarO has a substantial extracellular domain resembling a
      glove that contains all the divergent residues between the different isoforms.
      Liposome swelling experiments demonstrate that full-length CarO and a "loop-less"
      truncation mutant mediate small-molecule uptake at low levels but that they are
      unlikely to mediate passage of carbapenem antibiotics. These results are
      confirmed by biased molecular dynamics simulations that allowed us to
      quantitatively model the transport of selected small molecules. 

PMID- 25846138
TI  - Exploring the chemical space of quorum sensing peptides.
AB  - Quorum sensing peptides are signalling molecules that are produced by mainly gram
      positive bacteria. These peptides can exert different effects, ranging from intra
      and interspecies bacterial virulence to bacterial-host interactions. To better
      comprehend these functional differences, we explored their chemical space,
      bacterial species distribution and receptor-binding properties using multivariate
      data analyses, with information obtained from the Quorumpeps database. The quorum
      sensing peptides can be categorized into three main clusters, which, in turn, can
      be divided into several subclusters: the classification is based on
      characteristic chemical properties, including peptide size/compactness,
      hydrophilicity/lipophilicity, cyclization and the presence of (unnatural) S
      containing and aromatic amino acids. Most of the bacterial species synthesize
      peptides located into one cluster. However, some Streptococcus, Stapylococcus,
      Clostridium, Bacillus and Lactobacillus species produce peptides that are
      distributed over more than one cluster, with the quorum sensing peptides of
      Bacillus subtilis even occupying the total peptide space. The AgrC, FsrC and LamC
      receptors are only activated by cyclic (thio)lacton or lactam quorum sensing
      peptides, while the lipophilic isoprenyl-modified peptides solely bind the ComP
      receptor in Bacillus species.

PMID- 25846139
TI  - Nisin-induced expression of a recombinant antihypertensive peptide in dairy
      lactic acid bacteria.
AB  - OBJECTIVE: To improve the process for the production of milk-derived
      antihypertensive peptides, including a 12-residue peptide (FFVAPFPECVGK) from
      alphaS1-casein. RESULTS: A synthetic gene encoding this peptide was cloned within
      the pediocin operon, replacing the nucleic acid sequence encoding the mature
      pediocin peptide (papA) and resulting in a translational fusion between the
      pediocin leader peptide and the 12-residue hypotensive (C-12) peptide. The
      recombinant operon was subsequently cloned immediately downstream of the nisA
      promoter to allow for inducible gene expression within Streptococcus thermophilus
      ST128, Lactococcus lactis subsp. lactis ML3 and Lactobacillus casei C2. RT-PCR
      was used to confirm recombinant gene expression in complex medium; and SDS-PAGE
      analysis showed that the pediocin secretion machinery, encoded by papC and papD,
      allowed for secretion of the recombinant peptide from both L. lactis ML3 and L.
      casei C2 in a chemically defined medium. CONCLUSION: The use of a nisin as a
      "food-grade" inducer molecule, and generally-regarded-as-safe LAB species
      suggests that this system could be used for the production of functional food
      ingredients.

PMID- 25846140
TI  - Plate in situ hybridization (PISH) as a time and cost effective RNA expression
      assay to study phenotypic heterogeneity in a population of cultured murine cells
      at single cell resolution.
AB  - OBJECTIVES: Regenerative medicine approaches using reprogrammed or
      transdifferentiated cells require efficient single cell expression profiling to
      analyze culture homogeneity for quality control and recipients' safety. RESULTS:
      While antigen-antibody based systems have been developed for several proteins,
      probing at the mRNA level allows for more flexibility, faster adaption to the
      ever increasing new data from next generation sequencing and increased
      specificity, especially for genes of conserved gene families. CONCLUSIONS: We
      developed a time and cost effective expression profiling assay for monolayer cell
      culture in 96-well plates based on RNA in situ hybridization, termed PISH, at
      single cell resolution.

PMID- 25846141
TI  - Single-arm phase II trial design under parametric cure models.
AB  - The current practice of designing single-arm phase II survival trials is limited
      under the exponential model. Trial design under the exponential model may not be
      appropriate when a portion of patients are cured. There is no literature
      available for designing single-arm phase II trials under the parametric cure
      model. In this paper, a test statistic is proposed, and a sample size formula is
      derived for designing single-arm phase II trials under a class of parametric cure
      models. Extensive simulations showed that the proposed test and sample size
      formula perform very well under different scenarios.

PMID- 25846142
TI  - The nickel(II) complex of guanidinium phenyl porphyrin, a specific G-quadruplex
      ligand, targets telomeres and leads to POT1 mislocalization in culture cells.
AB  - With the aim of finding selective and biologically active G-quadruplex ligands,
      modified porphyrin with bulky cationic substituents, meso-5,10,15,20-tetrakis(4
      guanidinophenyl)porphyrin tetrahydrochloride, referred to as guanidinium phenyl
      porphyrin, was prepared. The corresponding nickel(II) and cobalt(III) metallated
      porphyrins were also synthesized. Interaction with quadruplexes was examined by
      means of fluorescence resonance energy transfer melting and surface plasmon
      resonance-based assays: the three compounds proved to bind to G-quadruplex DNA in
      a similar and highly selective way. Guanidinium phenyl porphyrin and its
      nickel(II) metallated derivative exhibit moderate cytotoxicity toward cells in
      culture. Strikingly, the nickel porphyrin derivative was able to displace hPOT1
      shelterin protein from telomeres in human cells. Nickel(II) guanidinium phenyl
      porphyrin, a cationic bulky porphyrin is a powerful specific G-quadruplex DNA
      ligand. It enters the cells and induces shelterin modification. 

PMID- 25846143
TI  - Intrinsic disorder and metal binding in UreG proteins from Archae
      hyperthermophiles: GTPase enzymes involved in the activation of Ni(II) dependent
      urease.
AB  - Urease is a Ni(II) enzyme present in every domain of life, in charge for nitrogen
      recycling through urea hydrolysis. Its activity requires the presence of two
      Ni(II) ions in the active site. These are delivered by the concerted action of
      four accessory proteins, named UreD, UreF, UreG and UreE. This process requires
      protein flexibility at different levels and some disorder-to-order transition
      events that coordinate the mechanism of protein-protein interaction. In
      particular, UreG, the GTPase in charge of nucleotide hydrolysis required for
      urease activation, presents a significant degree of intrinsic disorder, existing
      as a conformational ensemble featuring characteristics that recall a molten
      globule. Here, the folding properties of UreG were explored in Archaea
      hyperthermophiles, known to generally feature significantly low level of
      structural disorder in their proteome. UreG proteins from Methanocaldococcus
      jannaschii (Mj) and Metallosphaera sedula (Ms) were structurally and functionally
      analyzed by integrating circular dichroism, NMR, light scattering and enzymatic
      assays. Metal-binding properties were studied using isothermal titration
      calorimetry. The results indicate that, as the mesophilic counterparts, both
      proteins contain a significant amount of secondary structure but maintain a
      flexible fold and a low GTPase activity. As opposed to other UreGs, secondary
      structure is lost at high temperatures (68 and 75  degrees C, respectively) with
      an apparent two-state mechanism. Both proteins bind Zn(II) and Ni(II), with
      affinities two orders of magnitude higher for Zn(II) than for Ni(II). No major
      modifications of the average conformational ensemble are observed, but binding of
      Zn(II) yields a more compact dimeric form in MsUreG. 

PMID- 25846151
TI  - Two cases of transplant renal artery thrombosis and spontaneous rupture caused by
      mucormycosis.
AB  - Mucormycosis is an uncommon infectious complication after renal transplantation
      and is associated with fatal outcomes. We report 2 cases of transplant renal
      artery thrombosis and spontaneous rupture caused by mucormycosis. As stenosis,
      thrombosis, and spontaneous rupture of the transplant renal artery began to occur
      in both cases after renal transplantation, nephrectomy of the transplanted kidney
      was performed. Postoperative pathological findings in the transplanted kidney
      revealed an invasive mucormycosis infection in the renal artery. One patient
      survived, but the other patient died. This report also presents the diagnosis and
      treatment processes used for this transplant complication. 

PMID- 25846144
TI  - Ledipasvir and sofosbuvir in patients with genotype 1 hepatitis C virus infection
      and compensated cirrhosis: An integrated safety and efficacy analysis.
AB  - Patients with hepatitis C virus (HCV) infection and cirrhosis are
      underrepresented in clinical trials of interferon-free regimens of direct-acting
      antiviral agents, making it difficult to optimize therapy. We performed a post
      hoc analysis of data from seven clinical trials to evaluate the efficacy and
      safety of the fixed-dose combination of ledipasvir (LDV) and sofosbuvir (SOF),
      with and without ribavirin (RBV), in 513 treatment-naive and previously treated
      patients with genotype 1 HCV and compensated cirrhosis. All patients received LDV
      SOF for 12 or 24 weeks with or without RBV. We determined the rates of sustained
      virological response (SVR) 12 weeks after treatment (SVR12) overall and for
      subgroups. Of the 513 patients analyzed, 69% were previously treated and 47% had
      failed previous treatment with a protease-inhibitor regimen. Overall, 493
      patients (96%; 95% confidence interval [CI]: 94%-98%) achieved SVR12, 98% of
      treatment-naive and 95% of previously treated patients. SVR12 rates did not vary
      greatly by treatment duration (95% of patients receiving 12 weeks and 98% of
      patients receiving 24 weeks of treatment), nor by addition of RBV (95% of
      patients receiving LDV-SOF alone and 97% of those who received LDV-SOF plus RBV),
      although previously treated patients receiving 12 weeks of LDV-SOF without RBV
      had an SVR12 rate of 90%. One patient discontinued LDV-SOF because of an adverse
      event (AE). The most common AEs were headache (23%), fatigue (16%-19%), and
      asthenia (14%-16%). One patient (<1%) of those receiving LDV-SOF alone, and 4
      (2%) of those receiving LDV-SOF plus RBV had treatment-related serious AEs.
      CONCLUSIONS: This analysis suggests that 12 weeks of LDV-SOF is safe and
      effective for treatment-naive patients with HCV genotype 1 and compensated
      cirrhosis. The relatively lower SVR in treatment-experienced patients treated
      with 12 weeks of LDV-SOF raises the question of whether these patients would
      benefit from adding RBV or extending treatment duration to 24 weeks.

PMID- 25846152
TI  - Advanced waveforms and frequency with spinal cord stimulation: burst and high
      frequency energy delivery.
AB  - In recent years, software development has been key to the next generation of
      neuromodulation devices. In this review, we will describe the new strategies for
      electrical waveform delivery for spinal cord stimulation. A systematic literature
      review was performed using bibliographic databases, limited to the English
      language and human data, between 2010 and 2014. The literature search yielded
      three articles on burst stimulation and four articles on high-frequency
      stimulation. High-frequency and burst stimulation may offer advantages over tonic
      stimulation, as data suggest improved patient tolerance, comparable increase in
      function and possible success with a subset of patients refractory to tonic
      spinal cord stimulation. High-frequency and burst stimulation are new ways to
      deliver energy to the spinal cord that may offer advantages over tonic
      stimulation. These may offer new salvage strategies to mitigate spinal cord
      stimulation failure and improve cost-effectiveness by reducing explant rate. 

PMID- 25846154
TI  - Introduction: Putting law to work to improve public health: a national convening.

PMID- 25846155
TI  - Community experiments in public health law and policy.

PMID- 25846153
TI  - Deubiquitinating enzymes regulate Hes1 stability and neuronal differentiation.
AB  - Hairy and enhancer of split 1 (Hes1), a basic helix-loop-helix transcriptional
      repressor protein, regulates the maintenance of neural stem/progenitor cells by
      repressing proneural gene expression via Notch signaling. Previous studies showed
      that Hes1 expression oscillates in both mouse embryonic stem cells and neural
      stem cells, and that the oscillation contributes to their potency and
      differentiation fates. This oscillatory expression depends on the stability of
      Hes1, which is rapidly degraded by the ubiquitin/proteasome pathway. However, the
      detailed molecular mechanisms governing Hes1 stability remain unknown. We
      analyzed Hes1-interacting deubiquitinases purified from mouse embryonic stem
      cells using an Hes1-specific antibody, and identified the ubiquitin-specific
      protease 27x (Usp27x) as a new regulator of Hes1. We found that Hes1 was
      deubiquitinated and stabilized by Usp27x and its homologs ubiquitin-specific
      protease 22 (Usp22) and ubiquitin-specific protease 51 (Usp51). Knockdown of
      Usp22 shortened the half-life of Hes1, delayed its oscillation, and enhanced
      neuronal differentiation in mouse developing brain, whereas mis-expression of
      Usp27x reduced neuronal differentiation. These results suggest that these
      deubiquitinases modulate Hes1 protein dynamics by removing ubiquitin molecules,
      and thereby regulate neuronal differentiation of stem cells.

PMID- 25846156
TI  - Domestic legal preparedness and response to Ebola.

PMID- 25846157
TI  - Lessons learned from the expansion of naloxone access in Massachusetts and North
      Carolina.

PMID- 25846158
TI  - E-cigarettes: policy options and legal issues amidst uncertainty.

PMID- 25846159
TI  - Creating legal data for public health monitoring and evaluation: delphi standards
      for policy surveillance.

PMID- 25846160
TI  - Lessons from the residual newborn screening dried blood sample litigation.

PMID- 25846161
TI  - Shared use and safe routes to school: managing the fear of liability.

PMID- 25846162
TI  - Defining commercial speech in the context of food marketing.

PMID- 25846163
TI  - Navigating the incoherence of big data reform proposals.

PMID- 25846165
TI  - The Health in All Policies (HiAP) approach and the law: preliminary lessons from
      California and Chicago.

PMID- 25846164
TI  - The role of law in supporting secondary uses of electronic health information.

PMID- 25846166
TI  - Hospitals, collaboration, and community health improvement.

PMID- 25846167
TI  - Tribal water rights: exploring dam construction in Indian country.

PMID- 25846168
TI  - State health department employees, policy advocacy, and political campaigns:
      protections and limits under the law.

PMID- 25846169
TI  - Harnessing the public health power of model codes to increase drinking water
      access in schools and childcare.

PMID- 25846170
TI  - Adventures in nannydom: reclaiming collective action for the public's health.

PMID- 25846171
TI  - Mental health emergency detentions and access to firearms.

PMID- 25846172
TI  - Human health impacts of climate change: implications for the practice and law of
      public health.

PMID- 25846173
TI  - Is sharing de-identified data legal? The state of public health confidentiality
      laws and their interplay with statistical disclosure limitation techniques.

PMID- 25846174
TI  - The four stages of youth sports TBI Policymaking: engagement, enactment,
      research, and reform.

PMID- 25846175
TI  - Emergency preparedness and response for disabled individuals: implications of
      recent litigation.

PMID- 25846176
TI  - Bridging the gap between science and law: the example of tobacco regulatory
      science.

PMID- 25846177
TI  - From beginning to end: the importance of evidence-based policymaking in
      vaccination mandates.

PMID- 25846178
TI  - Legal challenges to the international deployment of government public health and
      medical personnel during public health emergencies: impact on national and global
      health security.

PMID- 25846179
TI  - Preterm birth and social inequality: assessing the effects of material and
      psychosocial disadvantage in a UK birth cohort.
AB  - OBJECTIVE: To examine the association between social inequalities and preterm
      birth, testing both psychosocial and material determinants. DESIGN: Retrospective
      cohort study with linked hospital data. SETTING AND POPULATION: 17 285 women in
      England, Scotland, Northern Ireland and Wales giving birth to singletons included
      in wave 1 of the UK Millennium Cohort Study. METHODS: Social inequalities were
      measured with material (household income, housing tenure) and psychosocial
      (education, occupational class, employment, social support) indicators. Analysis
      using multivariable logistic regression assessed odds of preterm birth, adjusting
      for demographics, health and health-related behaviors, pregnancy and delivery
      conditions, and pregnancy complications. MAIN OUTCOME MEASURE: Preterm birth
      between 24 and 36 weeks, 6 days' gestation. RESULTS: Initial bivariable analysis
      suggested associations between preterm birth and household income, housing
      tenure, and education. These effects were largely explained by adjustment for
      other social determinants in multivariable models. Following full adjustment,
      effects of unemployment [OR = 1.52, 95% confidence interval (CI) 1.21-1.90, p <
      0.001] and one indicator of poor social support (OR = 1.17, 95% CI 1.01-1.35, p =
      0.04) remained significant. CONCLUSION: Unemployment and lack of social support
      are associated with higher risk of preterm birth, supporting the hypothesis that
      poor psychosocial circumstances elevate a woman's risk of this adverse perinatal
      outcome. Further research is needed to examine the causal pathways through which
      social inequalities affect preterm birth.

PMID- 25846180
TI  - Environmental sustainability of bioethanol produced from sweet sorghum stem on
      saline-alkali land.
AB  - Life cycle assessment was conducted to evaluate the energy efficiency and
      environmental impacts of a bioethanol production system that uses sweet sorghum
      stem on saline-alkali land as feedstock. The system comprises a plant cultivation
      unit, a feedstock transport unit, and a bioethanol conversion unit, with 1000L of
      bioethanol as a functional unit. The net energy ratio is 3.84, and the net energy
      gain is 17.21MJ/L. Agrochemical production consumes 76.58% of the life cycle
      fossil energy. The category with the most significant impact on the environment
      is eutrophication, followed by acidification, fresh water aquatic ecotoxicity,
      human toxicity, and global warming. Allocation method, waste recycling approach,
      and soil salinity significantly influence the results. Using vinasse to produce
      pellet fuel for steam generation significantly improves energy efficiency and
      decreases negative environmental impacts. Promoting reasonable management
      practices to alleviate saline stress and increasing agrochemical utilization
      efficiency can further improve environmental sustainability. 

PMID- 25846181
TI  - Effects of feedstock ratio and organic loading rate on the anaerobic mesophilic
      co-digestion of rice straw and pig manure.
AB  - In order to investigate the effects of feedstock ratio and organic loading rate
      (OLR) on the anaerobic mesophilic co-digestion of rice straw (RS) and pig manure
      (PM), batch bottle tests (2.5L) were carried out at volatile solid (VS) ratios of
      0:1, 1:2, 1:1, 2:1, and 1:0 (RS/PM), and continuous bench experiments (40L) were
      carried out at OLRs of 3.0, 3.6, 4.2, 4.8, 6.0, 8.0, and 12.0kg VS/(m(3)d) with
      optimal VS ratio. The results showed that the optimal ratio was 1:1 in terms of
      biogas yield. Stable biogas production with an average specific biogas production
      of 413L/kg VS was obtained at an OLR of 3-8kg VS/(m(3)d). Anaerobic co-digestion
      was severely inhibited by the accumulation of volatile fatty acids when the OLR
      was 12kg VS/(m(3)d). Further, light and serious foaming were observed at OLR of 8
      and 12kg VS/(m(3)d), respectively. 

PMID- 25846182
TI  - High rate psychrophilic anaerobic digestion of undiluted dairy cow feces.
AB  - Novel high rate psychrophilic (20 degrees C) anaerobic digestion (PAD) of
      undiluted cow feces (11.5-13.5% total solids) was demonstrated using sequence
      batch reactor in long-term operation with successive cycles of 21days treatment
      cycle length (TCL). At organic loading rates (OLR) 9.0, 10.0, 11.0 and 12.0g TCOD
      kg(-1) inoculum d(-1) average specific methane yield (SMY) was 154.0+/-11.7,
      152.1+/-12.2, 126.0+/-2.8 and 116.0+/-6.1NL CH4 per kg of VS fed, respectively.
      Volatile solids removal averaged around 31.7+/-3.3%, 32.2+/-1.0%, 27.9+/-2.2% and
      23.4+/-0.5%, respectively. Substrate-to-inoculum ratio (SIR; wet-mass basis)
      ranged between 1.17+/-0.06 and 1.43+/-0.05. Concentration of volatile fatty acids
      in the bioreactors during the TCL indicated that hydrolysis was the rate limiting
      reaction. High rate PAD of undiluted cow feces is possible at OLR (g TCOD kg(-1)
      inoculum d(-1)) 9.0 and 10.0 with a TCL of 21days; however, OLR of 11.0 and 12.0
      are also possible but require longer TCL to maintain the SMY. 

PMID- 25846183
TI  - Effect of steam explosion on waste copier paper alone and in a mixed
      lignocellulosic substrate on saccharification and fermentation.
AB  - This study evaluated steam (SE) explosion on the saccharification and
      simultaneous saccharification and fermentation (SSF) of waste copier paper. SE
      resulted in a colouration, a reduction in fibre thickness and increased water
      absorption. Changes in chemical composition were evident at severities greater
      than 4.24 resulting in a loss of xylose and the production of breakdown products
      known to inhibit fermentation (particularly formic acid and acetic acid). SE did
      not improve final yields of glucose or ethanol, and at severities 4.53 and 4.83
      reduced yields probably due to the effect of breakdown products and fermentation
      inhibitors. However, at moderate severities of 3.6 and 3.9 there was an increase
      in initial rates of hydrolysis which may provide a basis for reducing processing
      times. Co-steam explosion of waste copier paper and wheat straw attenuated the
      production of breakdown products, and may also provide a basis for improving SSF
      of lignocellulose. 

PMID- 25846184
TI  - Continuous background light significantly increases flashing-light enhancement of
      photosynthesis and growth of microalgae.
AB  - Under specific conditions, flashing light enhances the photosynthesis rate in
      comparison to continuous illumination. Here we show that a combination of
      flashing light and continuous background light with the same integrated photon
      dose as continuous or flashing light alone can be used to significantly enhance
      photosynthesis and increase microalgae growth. To test this hypothesis, the green
      microalga Dunaliella salina was exposed to three different light regimes:
      continuous light, flashing light, and concomitant application of both. Algal
      growth was compared under three different integrated light quantities; low,
      intermediate, and moderately high. Under the combined light regime, there was a
      substantial increase in all algal growth parameters, with an enhanced
      photosynthesis rate, within 3days. Our strategy demonstrates a hitherto
      undescribed significant increase in photosynthesis and algal growth rates, which
      is beyond the increase by flashing light alone. 

PMID- 25846185
TI  - A biorefining process: Sequential, combinational lignocellulose pretreatment
      procedure for improving biobutanol production from sugarcane bagasse.
AB  - Here, for the first time, we designed a sequential, combinatorial lignocellulose
      pretreatment procedure (SCLPP) for microbial biofuel fermentation to reduce
      generation of microbial growth inhibitors and furthermore increase sugar yields.
      We tested this pretreatment process using sugarcane bagasse as substrate and
      assessed the effectiveness by analysis of biobutanol production through microbial
      clostridium beijerinckii NCIMB 8052 conversion. Our results showed that there
      were no inhibitory effects when using the hydrolysates as fermentation substrate.
      Under the SSF scheme, we observed the highest concentrations of butanol (6.4g/L)
      and total ABE (11.9g/L), resulting in a higher ABE productivity, compared with
      the SHF method. These findings suggest that the SCLPP is a feasible method for
      improving ABE production, lowering microbial inhibitor generation, and ensuring
      success in the subsequent fermentation process. Therefore, our work demonstrated
      developing a tractable integrated process that facilitates to increase biofuel
      production from agricultural residues rich in lignocellulose is feasible. 

PMID- 25846186
TI  - Comparative study of alkaline hydrogen peroxide and organosolv pretreatments of
      sugarcane bagasse to improve the overall sugar yield.
AB  - Green liquor (GL) combined with H2O2 (GL-H2O2) and green liquor (GL) combined
      with ethanol (GL-ethanol) were chosen for treating sugarcane bagasse. Results
      showed that the glucose yield (calculated from the glucose content as a
      percentage of the theoretical glucose available in the substrates)of sugarcane
      bagasse from GL-ethanol pretreatment (97.7%) was higher than that from GL-H2O2
      pretreatment (41.7%) after 72h hydrolysis with 18 filter paper unit (FPU)/g
      cellulose for cellulase, 27,175 cellobiase units (CBU)/g-cellulose for beta
      glucosidase. Furthermore, about 94.1% of xylan was converted to xylose after GL
      ethanol pretreatment without additional xylanase, while the xylose yield was only
      29.2% after GL-H2O2 pretreatment. Scanning electron microscopy showed that GL
      ethanol pretreatment could break up the fiber severely. Moreover, GL-ethanol
      pretreated substrate was more accessible to cellulase and more hydrophilic than
      that of GL-H2O2 pretreated. Therefore, GL-ethanol pretreatment is a promising
      method for improving the overall sugar (glucose and xylan) yield of sugarcane
      bagasse. 

PMID- 25846187
TI  - Production of d-lactic acid from hardwood pulp by mechanical milling followed by
      simultaneous saccharification and fermentation using metabolically engineered
      Lactobacillus plantarum.
AB  - This study focused on the process development for the d-lactic acid production
      from cellulosic feedstocks using the Lactobacillus plantarum mutant, genetically
      modified to produce optically pure d-lactic acid from both glucose and xylose.
      The simultaneous saccharification and fermentation (SSF) using delignified
      hardwood pulp (5-15% loads) resulted in the lactic acid titers of 55.2-84.6g/L
      after 72h and increased productivities of 1.77-2.61g/L/h. To facilitate the
      enzymatic saccharification of high-load pulp at a fermentation temperature, short
      term (?10min) pulverization of pulp was conducted, leading to a significantly
      improved saccharification with the suppressed formation of formic acid by
      product. The short-term milling followed by SSF resulted in a lactic acid titer
      of 102.3g/L, an optical purity of 99.2%, and a yield of 0.879g/g-sugars without
      fed-batch process control. Therefore, the process presented here shows promise
      for the production of high-titer d-lactic acid using the L. plantarum mutant. 

PMID- 25846188
TI  - Improvement on sugar cane bagasse hydrolysis using enzymatic mixture designed
      cocktail.
AB  - The aim of this work was to study cocktail supplementation for sugar cane bagasse
      hydrolysis, where the enzymes were provided from both commercial source and
      microorganism cultivation (Trichoderma reesei and genetically modified
      Escherichia coli), followed by purification. Experimental simplex lattice mixture
      design was performed to optimize the enzymatic proportion. The response was
      evaluated through hydrolysis microassays validated here. The optimized enzyme
      mixture, comprised of T. reesei fraction (80%), endoglucanase (10%) and beta
      glucosidase (10%), converted, theoretically, 72% of cellulose present in
      hydrothermally pretreated bagasse, whereas commercial Celluclast 1.5L converts
      49.11%+/-0.49. Thus, a rational enzyme mixture designed by using synergism
      concept and statistical analysis was capable of improving biomass
      saccharification. 

PMID- 25846189
TI  - The coupling of glycolysis and the Rubisco-based pathway through the non
      oxidative pentose phosphate pathway to achieve low carbon dioxide emission
      fermentation.
AB  - In this study, Rubisco-based engineered Escherichia coli, containing two
      heterologous enzymes of ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco)
      and phosphoribulokinase (PrkA), has been shown to be capable of the in situ
      recycling of carbon dioxide (CO2) during glycolysis. Two alternative approaches
      have been proposed to further enhance the carbon flow from glycolysis to a
      Rubisco-based pathway through the non-oxidative pentose phosphate pathway
      (NOPPP). The first is achieved by elevating the expression of transketolase I
      (TktA) and the second by blocking the native oxidation-decarboxylation reaction
      of E. coli by deleting the zwf gene from the chromosome (designated as JB/pTA and
      MZB, respectively). Decreases in the CO2 yield and the CO2 evolution per unit
      mole of ethanol production by at least 81% and 40% are observed. It is
      demonstrated in this study that the production of one mole of ethanol using E.
      coli strain MZB, the upper limit of CO2 emission is 0.052mol. 

PMID- 25846190
TI  - Multiple reuses of Rhodococcus ruber TH3 free cells to produce acrylamide in a
      membrane dispersion microreactor.
AB  - In this work, multiple reuses of Rhodococcus ruber TH3 free cells for the
      hydration of acrylonitrile to produce acrylamide in a membrane dispersion
      microreactor were carried out. Through using a centrifuge, the reactions reached
      39.9, 39.5, 38.6 and 38.0wt% of the final acrylamide product concentration
      respectively within 35min in a four cycle reuse of free cells. In contrast, using
      a stirring tank, free cells could only be used once with the same addition speed
      of acrylonitrile with a microreactor. Through observing the dissolution behavior
      of acrylonitrile microdroplets in a free cell solution using a coaxial
      microfluidic device and microscope, it was found that the acrylonitrile
      microdroplets with a diameter of 75MUm were rarely observed within a length of
      2cm channel within 10s, which illustrated that the microreactor can intensify the
      reaction rate to reduce the inhibition of acrylonitrile and acrylamide. 

PMID- 25846191
TI  - Measuring patient-centered care: An updated systematic review of how studies
      define and report concordance between patients' preferences and medical
      treatments.
AB  - OBJECTIVE: The purpose was to examine recent advances in measuring value
      concordance and to highlight best practices. METHODS: The paper updates a prior
      systematic review. A systematic review of the literature from 2008 to 2012
      identified articles that reported a relationship between patients' preferences
      concerning health outcomes and/or medical treatments, and treatment (intended or
      actual). Relevant articles were independently abstracted by two reviewers.
      RESULTS: The search identified 3635 unique citations, the full text of 187
      articles was examined, and 63 articles covering 61 studies were included, nearly
      a third more articles than identified in the original review. There were 72
      different value concordance calculations, the majority of which were clearly
      reported with significance. More studies assessed knowledge, reported on the
      association between value concordance and knowledge, and included a decision aid
      compared to those in the original review. CONCLUSION: There is increased
      reporting of value concordance in the literature. However, large differences
      exist in the way that the measure is defined and calculated. The variability
      makes it difficult to draw conclusions about the quality of care across studies.
      PRACTICE IMPLICATIONS: Value concordance is a critical component of patient
      centered care, and further attention is needed to establish standards for
      measurement and reporting.

PMID- 25846192
TI  - Out-of-office hours nurse-driven acute telephone counselling service in a large
      diabetes outpatient clinic: A mixed methods evaluation.
AB  - OBJECTIVE: To map the usage of out-of-office hours acute telephone counselling
      (ATC) provided by diabetes specialist nurses (n=18) for diabetes patients to
      explore potentials for improvement. METHODS: A mixed methods study involved
      mapping of ATC-usage during 6 months and a retrospective audit of frequent users.
      RESULTS: Altogether, 3197 calls were registered that were related to 592
      individual patients, corresponding to 10% of the population. Proportionally more
      users suffered from type 1 diabetes (p<0.001). ATC-users' mean HbA1c was 8.8% (73
      mmol/mol) compared to 8.1% (65 mmol/mol) for all patients attending the clinic
      (p<0.001). Hyperglycaemia was the most frequent reason for calling. The use of
      ATC likely prevented 15 admissions. More than half of the calls came from general
      nurses based in the community (n=619) and general nurses and nursing assistants
      based in care homes (n=1018). The majority (75%) of patients called less than
      five times. However, 8% called 16 times or more accounting for 52% of all calls.
      A retrospective audit identified them as physically and/or psychologically
      fragile patients. CONCLUSION: Hyperglycaemia was the most frequent reason for
      calling, and insulin dose adjustment the most frequent advice given. PRACTICE
      IMPLICATIONS: Frequent users identified need additional support.

PMID- 25846193
TI  - Let-7a inhibits growth and migration of breast cancer cells by targeting HMGA1.
AB  - Let-7 is one of the earliest discovered microRNAs (miRNAs) and has been reported
      to regulate self renewal and tumorigenicity of breast cancer cells. Let-7a is a
      member of this family and its function has not been fully characterized in breast
      cancer. First, total RNAs of breast cancer cells (MDA-MB-231, MCF-7), breast
      cancer tissues and corresponding adjacent normal tissues were extracted and used
      to detect let-7a expression by qRT-PCR. Secondly, the effects of let-7a on
      proliferation, colony formation, migration and invasion of breast cancer cells
      were assessed by in vitro cell culture experiments. Finally, western blotting was
      performed to demonstrate how let-7a regulated HMGA1 expression. We found that let
      7a expression was significantly lower in breast cancer cells and breast cancer
      tissues compared to corresponding adjacent normal tissues. Cell proliferation,
      colony formation, migration and invasion were decreased after overexpression of
      let-7a in breast cancer cells and vice versa. Furthermore, we identified the high
      mobility group A1 (HMGA1) as a potential target gene of let-7a. Protein
      expression of the target gene was significantly downregulated in let-7a mimic
      transfected breast cancer cells and significantly upregulated in let-7a inhibitor
      transfected breast cancer cells. Our data suggest that let-7a plays an important
      role as a tumor suppressor gene by targeting HMGA1, which may open novel
      perspectives for clinical treatments against breast cancer.

PMID- 25846194
TI  - Clinical, structural, biochemical and X-ray crystallographic correlates of
      pathogenicity for variants in the C-propeptide region of the COL3A1 gene.
AB  - Vascular Ehlers-Danlos syndrome (vEDS) is a heritable disorder of connective
      tissue caused by pathological variants in the COL3A1 gene, which encodes the
      alpha1 chain of type III collagen. Type III collagen is a major component of
      skin, arterial walls, and the gastrointestinal tract. Collagen III protein
      deficiency manifests as an increased risk of rupture, perforation, and dissection
      of these structures. The most disruptive gene variants affect the collagen helix
      via glycine substitutions or splice donor site mutations. The C-propeptide region
      of COL3A1 includes exons 49-52 and has a crucial role in initiating the C
      terminal assembly of procollagen monomers in the early stages of collagen
      biosynthesis. Nineteen COL3A1 variants have previously been reported in these
      exons, of which four were associated with a severe vEDS phenotype. We identified
      two novel C-propeptide missense variants; p.Pro1440Leu, p.Arg1432Leu, and a non
      stop mutation, c.4400A > T, p. (*1467Leuext*45). These variants produce variable
      phenotypes ranging from obvious acrogeria to classical or hypermobile EDS. A
      previously reported variant p.Lys1313Arg is of unknown clinical significance but
      likely benign, based on this study. Assigning disease pathogenicity remains
      complex, clinical phenotyping and crystal structure evidence being crucial. We
      briefly compare reported phenotypes for patients with missense variants in the C
      propeptide domain for other human collagen disorders including COL1A1 and COL1A2
      (osteogenesis imperfecta).

PMID- 25846196
TI  - A preliminary mapping of individual, relational, and social factors that impede
      disclosure of childhood sexual abuse.
AB  - Uncovering the pathways to disclosures of child sexual abuse (CSA) and the
      factors influencing the willingness of victims to talk about the abuse is
      paramount to the development of powerful practice and policy initiatives. Framed
      as a long interview method utilizing a grounded theory approach to analyze data,
      the objective of the current study was to provide a preliminary mapping of the
      barriers to CSA disclosures through an ecological systemic lens, from a sample of
      67 male and female CSA adult survivors, all of whom had recently received
      counselling services. The current project led to the identification of three
      broad categories of barriers that were each comprised of several subthemes,
      namely: Barriers from Within (internalized victim-blaming, mechanisms to protect
      oneself, and immature development at time of abuse); Barriers in Relation to
      Others (violence and dysfunction in the family, power dynamics, awareness of the
      impact of telling, and fragile social network); and Barriers in Relation to the
      Social World (labelling, taboo of sexuality, lack of services available, and
      culture or time period). This study points to the importance of using a broad
      ecological framework to understand the factors that inhibit disclosure of CSA, as
      barriers to disclosure do not constrain solely the victims. Results are discussed
      in light of their implications for research, prevention and intervention
      programs, and social policies and media campaigns, as the burden is on the larger
      community to create a climate of safety and transparency that makes the telling
      of CSA possible. 

PMID- 25846195
TI  - Life course pathways of adverse childhood experiences toward adult psychological
      well-being: A stress process analysis.
AB  - Growing evidence suggests that toxic stressors early in life not only convey
      developmental impacts but also augment risk of proliferating chains of additional
      stressors that can overwhelm individual coping and undermine recovery and health.
      Examining trauma within a life course stress process perspective, we posit that
      early childhood adversity carries a unique capacity to impair adult psychological
      well-being both independent of and cumulative with other contributors, including
      social disadvantage and stressful adult experiences. This study uses data from a
      representative population-based health survey (N=13,593) to provide one of the
      first multivariate assessments of unique, cumulative, and moderated effects of
      adverse childhood experiences (ACEs) toward explaining 3 related yet distinct
      measures of adult mental health: perceived well-being, psychological distress,
      and impaired daily activities. Results demonstrate support for each set of
      hypothesized associations, including exacerbation and amelioration of ACEs
      effects by adult stress and resilience resources, respectively. Implications for
      services and future research are discussed. 

PMID- 25846198
TI  - Studying abroad: Exploring factors influencing nursing students' decisions to
      apply for clinical placements in international settings.
AB  - BACKGROUND: For over 15 years the College of Nursing at the University of
      Saskatchewan has facilitated study abroad clinical placements in a number of
      countries to enhance student learning. Nursing students often find their study
      abroad experience to be a defining moment in their educational program, and in
      their personal and professional growth. OBJECTIVES: The main objective of this
      research was to explore factors influencing nursing students' decisions to study
      abroad. DESIGN: A descriptive longitudinal design study was conducted using an
      online survey. SETTINGS: The Study Abroad Survey was distributed to all
      undergraduate and graduate nursing students, in all years of all programs, at all
      sites of the College of Nursing, University of Saskatchewan in Saskatchewan,
      Canada. PARTICIPANTS: A total of 1058 nursing students registered in the 2013
      2014 academic year were surveyed. METHODS: The data were collected using an
      online survey administered by Campus LabsTM (2014). RESULTS: Students indicated
      that their interest in study abroad international experiences was high (84%),
      with many perceived benefits, but barriers to participation were also high for
      these students. Financial barriers topped the list (71%), followed by family
      responsibilities (30%) and job obligations (23%). CONCLUSION: The research
      highlights the factors behind student decision making related to international
      placements, and provides the basis for improvements to the College of Nursing's
      International Study Abroad Program (ISAP). Previous travel and international
      service learning, resulting in increased perceived value of a study abroad
      experience may prove to be the more significant factor influencing decision
      making, rather than financial barrier.

PMID- 25846197
TI  - Nurse teacher models in clinical education from the perspective of student nurses
      -A mixed method study.
AB  - OBJECTIVES: The aim was to describe and compare the clinical teacher's role in
      different models of clinical practice from the perspective of student nurses.
      DESIGN AND SETTINGS: The study took place in collaboration with two Swedish
      universities that applied different educational models in clinical practice. A
      mixed method approach was used. The quantitative part had a comparative design
      and the qualitative part had a descriptive design. PARTICIPANTS: The study group
      consisted of 114 student nurses (response rate 87%). Fifty-three of them had met
      clinical teachers employed at the university and not participating in the daily
      clinical work (University Nurse Teachers, UNTs), whilst 61 had met clinical
      teachers dividing their time between teaching and nursing (Clinical Nurse
      Teachers, CNTs). Eight students participated in the qualitative part of the
      study. METHODS: A questionnaire including the CLES+T scale was used to ascertain
      the students' perception of the clinical teacher's role, complemented by
      interviews directed towards an enrichment of this perception. RESULTS: Students
      meeting CNTs agreed more strongly than those meeting UNTs that the teacher had
      the ability to help them integrate theory and practice. Whilst spontaneous
      meetings between students and CNTs occurred, students mostly met UNTs in
      seminars. Students meeting UNTs felt alone but did appreciate having someone
      outside the clinical environment to provide support if they did not get along
      with their preceptor. CONCLUSIONS: In the case of UNTs, it is important that they
      keep their knowledge of clinical issues updated and visit the clinical placement
      not only for seminars but also to give students emotional support. In the case of
      CNTs, it is important that they are members of the faculty at the university,
      take part in the planning of the clinical courses and are able to explain the
      learning goals to the students.

PMID- 25846200
TI  - Antimicrobial and disinfectant resistance of Escherichia coli isolated from giant
      pandas.
AB  - AIMS: The study aims to demonstrate the antimicrobial and disinfectant resistance
      phenotypes and genotypes of Escherichia coli isolates obtained from giant pandas
      (Ailuropoda melanoleuca). METHODS AND RESULTS: Antimicrobial testing was
      performed according to the standard disk diffusion method. The minimal inhibitory
      concentrations (MICs) of disinfectants were determined using the agar dilution
      method. All isolates were screened for the presence of antimicrobial and
      disinfectant resistance genes and further analysed for genetic relatedness by
      pulse-field gel electrophoresis (PFGE). Results showed that 46.6% of the isolates
      were resistant to at least one antimicrobial. Escherichia coli isolates showed
      resistance to fewer antimicrobials as panda age increased. Among antimicrobial
      resistant E. coli isolates, the antimicrobial resistance genes blaCTX-M (88.2%)
      and sul1 (92.3%) were most prevalent. The disinfectant resistance genes emrE,
      ydgE/ydgF, mdfA and sugE(c) were commonly present (68.2-98.9%), whereas qac and
      sugE(p) were relatively less prevalent (0-21.3%). The frequencies of resistance
      genes tended to be higher in E. coli isolated in December than in July, and PFGE
      profiles were also more diverse in isolates in December. The qacEDelta1 and
      sugE(p) genes were higher in adolescent pandas than in any other age groups. PFGE
      revealed that antimicrobial resistance correlated well with sampling time and
      habitat. CONCLUSIONS: This study demonstrated that antimicrobial and disinfectant
      resistance was common in giant panda-derived E. coli, and the antimicrobial
      resistance was associated with sampling time and habitat. Escherichia coli could
      serve as a critical vector in spreading disinfectant and antimicrobial
      resistance. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first study that
      demonstrated the phenotypic and genetic characterizations of antimicrobial and
      disinfectant resistance in E. coli isolates from more than 60 giant pandas.
      Frequent transfer of pandas to other cages may lead to the dissemination of
      antimicrobial resistance. The study highlights the need for regularly monitoring
      the antimicrobial and disinfectant resistance in bacteria from giant pandas.

PMID- 25846201
TI  - Improving cold storage and processing traits in potato through targeted gene
      knockout.
AB  - Cold storage of potato tubers is commonly used to reduce sprouting and extend
      postharvest shelf life. However, cold temperature stimulates the accumulation of
      reducing sugars in potato tubers. Upon high-temperature processing, these
      reducing sugars react with free amino acids, resulting in brown, bitter-tasting
      products and elevated levels of acrylamide--a potential carcinogen. To minimize
      the accumulation of reducing sugars, RNA interference (RNAi) technology was used
      to silence the vacuolar invertase gene (VInv), which encodes a protein that
      breaks down sucrose to glucose and fructose. Because RNAi often results in
      incomplete gene silencing and requires the plant to be transgenic, here we used
      transcription activator-like effector nucleases (TALENs) to knockout VInv within
      the commercial potato variety, Ranger Russet. We isolated 18 plants containing
      mutations in at least one VInv allele, and five of these plants had mutations in
      all VInv alleles. Tubers from full VInv-knockout plants had undetectable levels
      of reducing sugars, and processed chips contained reduced levels of acrylamide
      and were lightly coloured. Furthermore, seven of the 18 modified plant lines
      appeared to contain no TALEN DNA insertions in the potato genome. These results
      provide a framework for using TALENs to quickly improve traits in commercially
      relevant autotetraploid potato lines.

PMID- 25846202
TI  - Authors' reply: Meat subtypes and their association with colorectal cancer:
      Systematic review and meta-analysis.

PMID- 25846203
TI  - Constraints to nitrogen acquisition of terrestrial plants under elevated CO2.
AB  - A key part of the uncertainty in terrestrial feedbacks on climate change is
      related to how and to what extent nitrogen (N) availability constrains the
      stimulation of terrestrial productivity by elevated CO2 (eCO2 ), and whether or
      not this constraint will become stronger over time. We explored the ecosystem
      scale relationship between responses of plant productivity and N acquisition to
      eCO2 in free-air CO2 enrichment (FACE) experiments in grassland, cropland and
      forest ecosystems and found that: (i) in all three ecosystem types, this
      relationship was positive, linear and strong (r(2) = 0.68), but exhibited a
      negative intercept such that plant N acquisition was decreased by 10% when eCO2
      caused neutral or modest changes in productivity. As the ecosystems were markedly
      N limited, plants with minimal productivity responses to eCO2 likely acquired
      less N than ambient CO2 -grown counterparts because access was decreased, and not
      because demand was lower. (ii) Plant N concentration was lower under eCO2 , and
      this decrease was independent of the presence or magnitude of eCO2 -induced
      productivity enhancement, refuting the long-held hypothesis that this effect
      results from growth dilution. (iii) Effects of eCO2 on productivity and N
      acquisition did not diminish over time, while the typical eCO2 -induced decrease
      in plant N concentration did. Our results suggest that, at the decennial
      timescale covered by FACE studies, N limitation of eCO2 -induced terrestrial
      productivity enhancement is associated with negative effects of eCO2 on plant N
      acquisition rather than with growth dilution of plant N or processes leading to
      progressive N limitation. 

PMID- 25846204
TI  - Acceleratory match-play demands of a Super Rugby team over a competitive season.
AB  - The match-play demands of rugby union have increased over time, and these demands
      should be quantified so as to provide a basis for optimal player loading during
      training. The primary aim of this article was to quantify accelerations,
      decelerations, impacts and aggregated body demands during the first half of match
      play in a Super Rugby team. The secondary aim was to determine whether these
      characteristics are position-specific. Thirty-three players were monitored for 14
      matches using global positioning system units with inbuilt microtechnology.
      Players were grouped according to positional roles and data were analysed for
      those who completed the entire duration of the first half of a given match.
      Forwards sustained more (d = 0.44) high-intensity impacts and greater (d = 0.26)
      aggregated body demands, while backs had more moderate (d = 0.55) and heavy
      accelerations (d = 0.76), and moderate (d = 0.23) and heavy decelerations (d =
      0.54). These differences suggest that conditioning and recovery strategies should
      reflect the physical demands placed on players in different playing positions.
      Forwards should be conditioned with a focus on impacts and require longer
      recovery for the same duration of playing time, whereas conditioning for backs
      should emphasise rapid accelerations and decelerations. 

PMID- 25846205
TI  - Toll-like receptors: Activation, signalling and transcriptional modulation.
AB  - Families of innate immune receptors serve as the bodies primary defence system by
      recognising and rapidly responding to infection by microorganisms or to
      endogenous danger signals and initiating inflammatory processes. Whilst Toll-like
      receptors (TLRs) were the first family to be discovered, important and exciting
      discoveries continue to emerge into the molecular mechanisms that control their
      activation and regulation. Herein, I will provide an overview of TLR activation
      and their downstream signalling cascades, and discuss some of the recent findings
      concerning the assembly of a TLR oligomeric signalling platform, known as the
      Myddosome. Further, a brief examination of the importance of crosstalk between
      multiple TLRs or between TLRs and other innate immune receptors for appropriate
      and coordinated immune responses will be presented. Finally, I will discuss the
      importance of mechanisms that regulate TLRs with a focus on the role of
      activating transcription factor 3 (ATF3) in modulating transcriptional responses
      downstream of TLRs. 

PMID- 25846206
TI  - Spreading the word: A process evaluation of a voluntary AOD prevention program.
AB  - BACKGROUND AND OBJECTIVES: Research on voluntary after-school alcohol and other
      drug (AOD) prevention programs is limited. It is important to increase
      understanding of students' motivation to attend these types of programs and their
      tendency to transfer program information to peers. This paper summarizes efforts
      to evaluate process information for CHOICE, a voluntary after-school AOD
      prevention program for middle-school youth. METHODS: A survey administered to
      1899 students aged 10-16 in seven schools assessed: (1) why students choose to
      attend CHOICE (2) barriers to attendance; and (3) how program information is
      disseminated to non-participants. Frequencies of responses from participants and
      non-participants were compared. RESULTS: Participants were motivated by several
      features, most notably, the demeanor of the group leaders and enjoyable
      curriculum content. Barriers to attendance were primarily logistic, but results
      also suggest that the promotion message should more effectively emphasize that
      CHOICE is appropriate for everyone. The majority of students knew about CHOICE,
      both through advertising and conversations with friends. Non-participants'
      detailed reports of what they heard from friends corresponded closely with what
      participants reported sharing. DISCUSSION AND CONCLUSIONS: The use of dynamic
      group leaders is critical to engaging students in voluntary programs. Offering
      the program on different days of the week or at different times (e.g., before
      school) may improve attendance rates. Peer networks represent a critical pathway
      for prevention information that can help increase program impact. SCIENTIFIC
      SIGNIFICANCE: These results can be used to inform modifications to existing
      voluntary after-school AOD prevention programs to obtain higher attendance rates
      and more widespread dissemination of the intervention message.

PMID- 25846207
TI  - Age-related expression analysis of mouse liver nuclear protein binding to 3'
      untranslated region of Period2 gene.
AB  - In mammals, both circadian rhythm and aging play important roles in regulating
      time-dependent homeostasis. We previously discovered an age-related increase
      element binding protein, hnRNP A3, which binds to the 3'-untranslated region
      (UTR) of blood coagulation factor IX (FIX). Here, we describe other members of
      this protein family, hnRNP C and hnRNP H, which bind to the 3'-UTR of the mouse
      circadian clock gene Period 2 (mPer2). RNA electrophoretic mobility shift assays
      using a (32)P-labeled Per2 RNA probe coupled with two-dimensional gel
      electrophoresis followed by MALDI-TOF/MS peptide mass fingerprint analysis was
      used to analyze these proteins. Western blotting suggested that the total
      expression of these proteins in mouse liver cell nuclei does not increase with
      age. Two-dimensional gel electrophoresis analysis of age-related protein
      expression showed that many isoforms of these proteins exist in the liver and
      that each protein exhibits a complex age-related expression pattern. These
      results suggest that many isoforms of proteins are regulated by different aging
      systems and that many age regulation systems function in the liver. 

PMID- 25846208
TI  - Positive selection drives the evolution of a major histocompatibility complex
      gene in an endangered Mexican salamander species complex.
AB  - Immune gene evolution can be critical to species survival in the face of
      infectious disease. In particular, polymorphism in the genes of the major
      histocompatibility complex (MHC) helps vertebrates combat novel and diverse
      pathogens by increasing the number of pathogen-derived proteins that can initiate
      the host's acquired immune response. In this study, we used a combination of
      presumably adaptive and neutral markers to investigate MHC evolution in
      populations of five salamander species within the Ambystoma velasci complex, a
      group consisting of 15 recently diverged species, several of which are
      endangered. We isolated 31 unique MHC class II beta alleles from 75 total
      individuals from five species in this complex. MHC heterozygosity was
      significantly lower than expected for all five species, and we found no clear
      relationship between number of MHC alleles and species range, life history, or
      level of heterozygosity. We inferred a phylogeny representing the evolutionary
      history of Ambystoma MHC, with which we found signatures of positive selection on
      the overall gene, putative peptide-binding residues, and allelic lineages. We
      identified several instances of trans-species polymorphism, a hallmark of
      balancing selection observed in other groups of closely related species. In
      contrast, we did not detect comparable allelic diversity or signatures of
      selection on neutral loci. Additionally, we identified 17 supertypes among the 44
      unique Ambystoma alleles, indicating that these sequences may encode functionally
      distinct MHC variants. We therefore have strong evidence that positive selection
      is a major evolutionary force driving patterns of MHC polymorphism in this
      recently radiated species complex. 

PMID- 25846209
TI  - Development and evaluation of a sublingual tablet based on recombinant Bet v 1 in
      birch pollen-allergic patients.
AB  - BACKGROUND: Sublingual immunotherapy (SLIT) applied to type I respiratory
      allergies is commonly performed with natural allergen extracts. Herein, we
      developed a sublingual tablet made of pharmaceutical-grade recombinant Bet v
      1.0101 (rBet v 1) and investigated its clinical safety and efficacy in birch
      pollen (BP)-allergic patients. METHODS: Following expression in Escherichia coli
      and purification, rBet v 1 was characterized using chromatography, capillary
      electrophoresis, circular dichroism, mass spectrometry and crystallography.
      Safety and efficacy of rBet v 1 formulated as a sublingual tablet were assessed
      in a multicentre, double-blind, placebo-controlled study conducted in 483
      patients with BP-induced rhinoconjunctivitis. RESULTS: In-depth characterization
      confirmed the intact product structure and high purity of GMP-grade rBet v 1. The
      crystal structure resolved at 1.2 A documented the natural conformation of the
      molecule. Native or oxidized forms of rBet v 1 did not induce the production of
      any proinflammatory cytokine by blood dendritic cells or mononuclear cells. Bet v
      1 tablets were well tolerated by patients, consistent with the known safety
      profile of SLIT. The average adjusted symptom scores were significantly decreased
      relative to placebo in patients receiving once daily for 5 months rBet v 1
      tablets, with a mean difference of 17.0-17.7% relative to the group treated with
      placebo (P < 0.025), without any influence of the dose in the range (12.5-50 MUg)
      tested. CONCLUSION: Recombinant Bet v 1 has been produced as a well-characterized
      pharmaceutical-grade biological drug. Sublingual administration of rBet v 1
      tablets is safe and efficacious in patients with BP allergic rhinoconjunctivitis.

PMID- 25846210
TI  - Intrinsically disordered cytoplasmic domains of two cytokine receptors mediate
      conserved interactions with membranes.
AB  - Class 1 cytokine receptors regulate essential biological processes through
      complex intracellular signalling networks. However, the structural platform for
      understanding their functions is currently incomplete as structure-function
      studies of the intracellular domains (ICDs) are critically lacking. The present
      study provides the first comprehensive structural characterization of any
      cytokine receptor ICD and demonstrates that the human prolactin (PRL) receptor
      (PRLR) and growth hormone receptor (GHR) ICDs are intrinsically disordered
      throughout their entire lengths. We show that they interact specifically with
      hallmark lipids of the inner plasma membrane leaflet through conserved motifs
      resembling immuno receptor tyrosine-based activation motifs (ITAMs). However,
      contrary to the observations made for ITAMs, lipid association of the PRLR and
      GHR ICDs was shown to be unaccompanied by changes in transient secondary
      structure and independent of tyrosine phosphorylation. The results of the present
      study provide a new structural platform for studying class 1 cytokine receptors
      and may implicate the membrane as an active component regulating intracellular
      signalling. 

PMID- 25846211
TI  - Nutritional supplementation and artificial reproductive technique (ART) outcomes.
AB  - Approximately one in six couples suffer from subfertility, and many seek
      treatment with artificial reproductive technologies (ART). Despite improvements
      in laboratory techniques and ovarian stimulation, ongoing pregnancy rates per
      cycle remain at ~25%. Couples wanting to improve their chances may turn to
      adjuvant therapies, such as nutritional supplements. There is growing evidence
      that periconceptional nutritional status is a key determinant of fertility and
      long-term health of the offspring, and a lucrative market has developed to meet
      the demand based on these benefits. However, the practice of routine dietary
      supplementation before and during IVF treatment has not been subject to well
      powered prospective randomised trials. In this article, the potential roles of
      specific nutritional supplements in the context of improving IVF outcomes are
      reviewed and an assessment is made of the evidence base supporting their clinical
      use in this context. Finally, current research needs in the field are outlined. 

PMID- 25846212
TI  - Selenoprotein Genes Exhibit Differential Expression Patterns Between Hepatoma
      HepG2 and Normal Hepatocytes LO2 Cell Lines.
AB  - The purpose of this study was to compare messenger RNA (mRNA) expression of
      selenoprotein genes between hepatoma HepG2 and normal hepatocytes LO2 cell lines.
      Liver HepG2 and LO2 cells were cultured in 12-well plates under the same
      condition until cells grew to complete confluence, and then cells were harvested
      for total RNA and protein extraction. The qPCRs were performed to compare gene
      expression of 14 selenoprotein genes and 5 cancer signaling-related genes. Enzyme
      activities were also assayed. The results showed that human hepatoma HepG2 cells
      grew faster than normal hepatocytes LO2 cells. Among the genes investigated, 10
      selenoprotein genes (Gpx1, Gpx3, Gpx4, Selx, Sepp, Sepw1, Sepn1, Selt, Seli,
      Selh) and 3 cancer signaling-related genes (Bcl-2A, caspase-3, and P38) were
      upregulated (P < 0.05), while Selo and Bcl-2B were downregulated (P < 0.05) in
      hepatoma HepG2 cells compared to LO2 cells. Significant correlations were found
      between selenoprotein genes and the cancer signaling-related genes Caspase3, P53,
      Bc1-2A, and Bc1-2B. Our results revealed that selenoprotein genes were aberrantly
      expressed in hepatoma HepG2 cells compared to normal liver LO2 cells, which
      indicated that those selenoprotein genes may play important roles in the
      occurrence and development of liver carcinogenesis.

PMID- 25846213
TI  - Effects of Boric Acid on Fracture Healing: An Experimental Study.
AB  - Boric acid (BA) has positive effects on bone tissue. In this study, the effects
      of BA on fracture healing were evaluated in an animal model. Standard closed
      femoral shaft fractures were created in 40 male Sprague-Dawley rats under general
      anesthesia. The rats were allocated into five groups (n = 8 each): group 1,
      control with no BA; groups 2 and 3, oral BA at doses of 4 and 8 mg/kg/day,
      respectively; group 4, local BA (8 mg/kg); and group 5, both oral and local BA (8
      mg/kg/day orally and 8 mg/kg locally). After closed fracture creation, the
      fracture line was opened with a mini-incision, and BA was locally administered to
      the fracture area in groups 4 and 5. In groups 2, 3, and 5, BA was administered
      by gastric gavage daily until sacrifice. The rats were evaluated by clinical,
      radiological, and histological examinations. The control group (group 1)
      significantly differed from the local BA-exposed groups (groups 4 and 5) in the
      clinical evaluation. Front-rear and lateral radiographs revealed significant
      differences between the local BA-exposed groups and the control and other groups
      (p < 0.05). Clinical and radiological evaluations demonstrated adequate agreement
      between observers. The average histological scores significantly differed across
      groups (p = 0.007) and were significantly higher in groups 4 and 5 which were the
      local BA (8 mg/kg) and both oral and local BA (8 mg/kg/day orally and 8 mg/kg
      locally), respectively, compared to the controls. This study suggests that BA may
      be useful in fracture healing. Further research is required to demonstrate the
      most effective local dosage and possible use of BA-coated implants.

PMID- 25846214
TI  - Stroke in Bahrain: rising incidence, multiple risk factors, and suboptimal care.
AB  - The incidence of stroke in Bahrain is rising in the Bahraini population and has
      nearly doubled over the last 16 years, while the incidence in the non-Bahraini
      population has not changed. Incidence of stroke in the Bahraini population
      (110/100,000) is now much greater than in the non-Bahraini population
      (27/100,000). The Bahraini stroke population is 10 years younger than Western
      comparators with a much higher prevalence of many of the risk factors for stroke,
      including diabetes (54%), hypertension (75%) and hyperlipidemia (34%). The
      combination of an ageing Bahraini population alongside a high prevalence of risk
      factors suggests a 'ticking time bomb' that is likely to see a continuing rise in
      the incidence of stroke. The quality of risk factor prevention and hospital-based
      stroke care is therefore crucial in Bahrain. While 88% of patients were scanned
      within 24 h and 86% with non-haemorrhagic strokes were commenced on aspirin
      within 48 h, none of the patients received thrombolysis or were admitted to a
      stroke unit. Improvement of stroke outcomes in Bahrain could be achieved through
      implementation of evidence-based measures, including improved risk factor
      management in primary care and stroke units and thrombolysis in secondary care.

PMID- 25846215
TI  - Increased risk for atypical fractures associated with bisphosphonate use.
AB  - BACKGROUND: Studies suggest an increasing occurrence of atypical femoral
      fractures with the use of bisphosphonates. OBJECTIVE: To examine whether the use
      of bisphosphonates increases the risk for atypical fractures. DESIGN: Systematic
      review and meta-analysis. DATA SOURCES: Literature search of MEDLINE, Embase and
      Cochrane CENTRAL (1948-June 2013). REVIEW METHODS:  SELECTION CRITERIA: (i)
      randomized controlled trial or an observational study, (ii) evaluated
      bisphosphonate therapy versus no treatment and (iii) reported an incidence of
      subtrochanteric or diaphyseal fracture individually, or a composite of both. Two
      independent investigators completed study selection, data extraction and validity
      assessment. The Cochrane Risk of Bias Tool was used to assess the quality of
      included studies. RESULTS: Ten (n = 658497) studies were included in the meta
      analysis which demonstrated a statistically significant increased risk of
      subtrochanteric or diaphyseal fracture with bisphosphonate use [adjusted odds
      ratios (AOR) = 1.99, 95% confidence intervals (CI)= 1.28-3.10] with I (2) = 84.3%
      (95% CI = 73.5%-89.5%) and Egger P = 0.01. Subtrochanteric fractures showed an
      AOR = 2.71 (95% CI = 1.86-3.95) with I (2) = 83.6% (95% CI = 64.3%-90.3%) and
      Egger's P = 2.29. Diaphyseal fractures had an AOR = 2.06 (95% CI = 1.70-2.50), I
      (2) = 29.7% (95% CI = 0%-73.7%) and Egger's P = 1.22. CONCLUSION: Results suggest
      there is an increased risk for atypical fractures associated with bisphosphonates
      and raises awareness to the potential complications related with bisphosphonates.
      These findings warrant the comprehensive evaluation of patients before initiating
      bisphosphonate therapy and highlights the need for additional medical decision
      analyses in future studies to compare the benefit over potential harms of
      bisphosphonate therapy.

PMID- 25846216
TI  - Mental health symptoms and patient-reported diabetes symptom burden: implications
      for medication regimen changes.
AB  - AIMS: To examine the relative contribution of glycaemic control (HbA1C) and
      depressive symptoms on diabetes-related symptom burden (hypoglycaemia and
      hyperglycaemia) in order to guide medication modification. METHODS: Secondary
      analysis of medical records data and questionnaires collected from a
      racially/ethnically diverse sample of adult patients with type 2 diabetes (n =
      710) from seven outpatient clinics affiliated with an academic medical centre
      over a 1-year period as part of the Reducing Racial Disparities in Diabetes:
      Coached Care (R2D2C2) study. RESULTS: Results from linear regression analysis
      revealed that patients with high levels of depressive symptoms had more diabetes
      related symptom burden (both hypoglycaemia and hyperglycaemia) than patients with
      low levels of depressive symptoms (betas = 0.09-0.17, Ps < 0.02). Furthermore,
      results from two logistic regression analyses suggested that the odds of regimen
      intensification at 1-year follow-up was marginally associated with patient
      reported symptoms of hypoglycaemia [adjusted odds ratio (aOR) = 1.24, 95% CI:
      0.98-1.58; P = 0.08] and hyperglycaemia (aOR = 1.21, 95% CI: 1.00-1.46; P =
      0.05), after controlling for patients' HbA1C, comorbidity, insulin use and
      demographics. These associations, however, were diminished for patients with high
      self-reported hypoglycaemia and high levels of depressive symptoms, but not low
      depressive symptoms (interaction terms for hypoglycaemia by depressive symptoms,
      aOR = 0.98, 95% CI: 0.97-0.99; P = 0.03). CONCLUSIONS: Mental health symptoms are
      associated with higher levels of patient-reported of diabetes-related symptoms,
      but the association between diabetes-related symptoms and subsequent regimen
      modifications is diminished in patients with greater depressive symptoms.
      Clinicians should focus attention on identifying and treating patients' mental
      health concerns in order to address the role of diabetes-related symptom burden
      in guiding physician medication prescribing behaviour.

PMID- 25846218
TI  - Osteoarthritis in perspective.

PMID- 25846217
TI  - Nanostructured gellan and xanthan hydrogel depot integrated within a baghdadite
      scaffold augments bone regeneration.
AB  - Controlled delivery of biological cues through synthetic scaffolds to enhance the
      healing capacity of bone defects is yet to be realized clinically. The purpose of
      this study was development of a bioactive tissue-engineered scaffold providing
      the sustained delivery of an osteoinductive drug, dexamethasone disodium
      phosphate (DXP), encapsulated within chitosan nanoparticles (CN). Porous
      baghdadite (BD; Ca3 ZrSi2 O9 ) scaffolds, a zirconia-modified calcium silicate
      ceramic, was coated with DXP-encapsulated CN nanoparticles (DXP-CN) using
      nanostructured gellan and xanthan hydrogel (GX). Crosslinker and GX polymer
      concentrations were optimized to achieve a homogeneous distribution of hydrogel
      coating within BD scaffolds. Dynamic laser scattering indicated an average size
      of 521 +/- 21 nm for the DXP-CN nanoparticles. In vitro drug-release studies
      demonstrated that the developed DXP-CN-GX hydrogel-coated BD scaffolds (DXP-CN-GX
      BD) resulted in a sustained delivery of DXP over the 5 days (78 +/- 6% of drug
      release) compared with burst release over 1 h, seen from free DXP loaded in
      uncoated BD scaffolds (92 +/- 8% release in 1 h). To estimate the influence of
      controlled delivery of DXP from the developed scaffolds, the effect on MG 63
      cells was evaluated using various bone differentiation assays. Cell culture
      within DXP-CN-GX-BD scaffolds demonstrated a significant increase in the
      expression of early and late osteogenic markers of alkaline phosphatase activity,
      collagen type 1 and osteocalcin, compared to the uncoated BD scaffold. The
      results suggest that the DXP-releasing nanostructured hydrogel integrated within
      the BD scaffold caused sustained release of DXP, improving the potential for
      osteogenic differentiation. Copyright (c) 2015 John Wiley & Sons, Ltd.

PMID- 25846219
TI  - Developing an evidence-based nursing protocol on wound drain management for total
      joint arthroplasty.
AB  - BACKGROUND: Although various drains have long been used for many years in total
      joint replacement, there is a paucity of evidence for the benefit of drain
      applications. Evidence suggests inconsistent practice in the use of drainage
      systems, whether intermittently applying suction or free of suction in the
      application of drainage systems, as well as the optimal timing for wound drain
      removal. AIM: It aimed to perform a systematic review to develop an evidence
      based nursing protocol to manage wound drainage following total joint
      arthroplasty. METHODS: A comprehensive systematic review of available evidence up
      to 2013. Searches of the EMBASE, Cochrane library, CINAHL, Medline electronic
      databases and an internet search by Yahoo and Google engine returned 2840
      records, of which 11 met the inclusion criteria for this review. A further two
      papers were obtained through scanning the reference lists of those articles
      included from the initial literature search. RESULTS: Different clamping times
      were retrieved from the literature. A protocol was adapted for clinical
      application according to the summary of the retrieved information. It is
      suggested that clamping is performed 1 h after the insertion of suction drains
      post-operatively in the operating theatre. Wound drains should be clamped for 1 h
      if blood loss is more than 600 ml in 6 h in first 24 h. Wound drains should be
      clamped for 1 h if blood loss is more than 800 ml in 8 h thereafter. It is
      suggested that the drainage reservoir bottle should be mark and findings recorded
      in line with the principle of drain clamping. This means that the amount of
      drainage is measured and recorded every 6 h in first 24 h and every 8 h
      thereafter. It is suggested that wound drains should be remove before 48 h after
      TJR. If blood loss is less than 50 ml in past 6 h or less than 70 ml in past 8 h,
      the drain should be remove and the wound site should be monitored closely.
      CONCLUSION: This paper has guided nurses to develop an evidence-based protocol to
      improve patient care on wound drain management. Further study is necessary to
      evaluate the effectiveness of the protocol.

PMID- 25846220
TI  - Orthopaedic nurses' attitudes towards clinical nursing research - A cross
      sectional survey.
AB  - The call for evidence-based knowledge in clinical nursing practice has increased
      during recent decades and research in orthopaedic nursing is needed to improve
      patients' conditions, care and treatment. A descriptive cross-sectional survey
      was conducted to determine the self-perceived theoretical knowledge and practical
      research competencies among orthopaedic nurses and their interest and motivation
      to increase these in everyday practice. A newly developed questionnaire was given
      to a convenience sample of 87 orthopaedic nurses. Forty three orthopaedic nurses
      (49.4%) completed the questionnaire. The results indicated that despite the
      majority of orthopaedic nurses having low self-perceived theoretical knowledge
      and practical research competencies, their interest and motivation to improve
      these were high, especially their inner motivation. However, the nurses' inner
      motivation was inhibited by a lack of acceptance from colleagues and section head
      nurses and a shortage of time. This study forms a baseline as a part of a larger
      study and contributes knowledge useful to other orthopaedic departments with an
      interest in optimizing nursing research to improve orthopaedic nursing care
      quality.

PMID- 25846221
TI  - Developing a programme of patient 'streaming' in an emergency department.
AB  - Orthopaedic and musculoskeletal injuries are commonly identified in the emergency
      department (ED). Whilst much orthopaedic trauma literature focuses on fractures
      of the proximal femur, raising key issues such as length of stay and timely
      discharge, the start of the patients' journey is just as important in ensuring an
      appropriate assessment and a smooth transition through each stage of care. In the
      UK targets have been set for proximal hip fractured patients to attend theatre
      within 48 hours of admission, if fit. Appraising such patients expediently on
      initial point of contact in the ED has demonstrated that a number of factors can
      impinge and delay the patients' progress. This said a large number of other
      orthopaedic and musculoskeletal self presenting patients rely on the same
      appropriate transition to suitable medical assistance. The emergency department
      triage system has been used in the UK in its latest format since 2001, yet
      elderly patients with painful Colles fractures find they wait for specialist
      attention in a linear queue, possibly over extended lengths of time. This short
      paper explores how 'streaming' patients in one local ED has improved
      waiting/treatment times, and identified the fact that in some months (December
      2012), 1 in 3 attendees present with a musculoskeletal problem. Using audit data
      collected over the last four years the benefits of 'streaming' patients is
      evident.

PMID- 25846222
TI  - Bowel management post major joint arthroplasty: results from a randomised
      controlled trial.
AB  - AIM: To evaluate the effect of a new post-operative bowel protocol in total hip
      and total knee replacement patients. BACKGROUND: Up to 65% of total hip and total
      knee replacement patients experience some degree of constipation post
      operatively. A lack of robust evidence to guide bowel management and reduce
      constipation in this cohort was the impetus for this study. DESIGN: A multisite
      cluster randomised trial in private secondary and tertiary hospitals. METHODS: In
      total 331 patients were recruited across seven Australian hospitals over 13
      months. Control participants (n = 171) received routine bowel management whilst
      intervention participants (n = 160) received bowel management as per the trial
      protocol. RESULTS: Intervention patients took 6 days less than controls to return
      to normal bowel function, and were more than seven times more likely to return to
      normal bowel function by day 5 post operatively. Age, gender and length of pre
      operative fasting had no effect on these outcomes. CONCLUSION: These results
      support the use of the Murdoch Bowel Protocol((r)) for hip and knee replacement
      patients and may be relevant for other patient groups who experience opioid
      induced bowel dysfunction.

PMID- 25846223
TI  - A longitudinal study of quality of life and functional status in total hip and
      total knee replacement patients.
AB  - BACKGROUND: Primary total hip and primary total knee surgeries are commonly
      performed to improve patients' quality of life and functional status. AIM: This
      longitudinal retrospective study (N = 851) examined self-reported quality of life
      and functional status over the preoperative and postoperative periods: 12 months
      prior to surgery, one month prior to surgery and 12 months following surgery.
      METHODS: A linear mixed effects model was used to analyze the changes in quality
      of life and functional status over the sampling period. RESULTS: Patients in the
      convenience sample reported improvements in quality of life and functional status
      utilizing the SF-12 and Oxford Hip and Oxford Knee, although differences were
      noted by procedure and gender. Total hip patients tended to demonstrate greater
      improvement than total knee patients and males reported higher levels of physical
      and mental quality of life as well as functional status when compared to females.
      Of particular note was that mental health scores were consistently lower in both
      total hip and total knee replacement patients across the perioperative period and
      up to one year postoperative. CONCLUSION: This study identifies an opportunity
      for health care providers to proactively address the mental health of total hip
      and total knee replacement patients throughout their joint replacement
      trajectory.

PMID- 25846226
TI  - Alpha-synuclein modulates NR2B-containing NMDA receptors and decreases their
      levels after rotenone exposure.
AB  - Alpha-synuclein (alpha-syn) is the main protein component of Lewy bodies (LBs),
      that together with nigrostriatal dopamine neuron loss constitute typical
      pathological hallmarks of Parkinson's disease (PD). Glutamate N-methyl-d
      aspartate receptor (NMDAR) abnormalities, peculiarly involving NR2B-containing
      NMDAR, have been observed in the brain of PD patients and in several experimental
      models of the disease. Recent findings, indicating that alpha-syn can modulate
      NMDAR trafficking and function, suggest that this protein may be a pivotal
      regulator of NMDAR activity. Prompted by these evidences, we used fluorescence
      immunocytochemistry, western blotting and ratiometric Ca(2+) measurements to
      investigate whether wild type (wt) or C-terminally truncated alpha-syn can
      specifically modulate NR2B-containing NMDAR levels, subcellular trafficking and
      function. In addition, we evaluated whether the exposure of primary cortical
      neurons to increasing concentrations of rotenone could differentially regulate
      NR2B levels and cell viability in the presence or in the absence of alpha-syn.
      Our results indicate that both wt and C-terminally truncated alpha-syn negatively
      modulate NR2B-containing NMDAR levels, membrane translocation and function.
      Moreover, we found that absence of alpha-syn abolishes the rotenone-dependent
      decrease of NR2B levels and reduces neuronal vulnerability in primary cortical
      neurons. These findings suggest that alpha-syn can modulate neuronal resilience
      by regulating NR2B-containing NMDAR, whose specific alterations could connect
      alpha-syn pathology to neuronal degeneration in PD. 

PMID- 25846227
TI  - Learning Process During Risk Detection in Adolescents With ADHD.
AB  - OBJECTIVE: To evaluate and describe the performance during the learning process
      of risk-detection versus risk-benefit processing in adolescents diagnosed with
      ADHD. METHOD: Thirty-five adolescents with ADHD and 26 paired controls
      participated. The tests applied are Iowa-type children version paradigm and
      Stroop test. RESULTS: Adolescents with ADHD exhibited lower risk-benefit
      processing capacity and lower ability to detect risk selections; main findings
      also indicate that adolescents with ADHD were slower to learn to avoid risk
      choices. In addition, they also presented a deficient inhibitory control.
      CONCLUSION: Results confirm the presence of a deficit in advantageous choice in
      adolescents with ADHD. By providing a measure of risk choice-and not only a net
      score-we show that adolescents with ADHD also fail to avoid risk choices. This
      deficit is mainly because they are slower in learning how to avoid risk choices,
      and not simply deficient. Literature is scarce concerning studies with Iowa-type
      paradigms in samples intregated exclusively by adolescents. More research is
      needed to clarify the nature of these deficiencies.

PMID- 25846228
TI  - Association of the Conners' Kiddie Continuous Performance Test (K-CPT)
      Performance and Parent-Report Measures of Behavior and Executive Functioning.
AB  - OBJECTIVE: To explore the relationship between the Conners' Kiddie Continuous
      Performance Test (K-CPT) performance and parent-report measures of child behavior
      and executive functioning, and clarify the role of sex in K-CPT performance in
      preschoolers. METHOD: Mothers and children recruited to the Health Outcomes and
      Measures of the Environment Study with complete 5-year assessment data relevant
      to the analyses were included ( N = 127). We examined the association between K
      CPT scores and Behavior Assessment System for Children-Second Edition (BASC-2)
      and Behavior Rating Inventory of Executive Function (BRIEF) scores, with
      covariate adjustment. RESULTS: We found no significant associations between K
      CPT, BASC-2, and BRIEF scores in the full sample. In sex-stratified analyses, we
      found unusually fast reaction time on K-CPT was related to executive control
      difficulties in girls, whereas unusually slow reaction time was related to the
      same difficulties in boys. Omission errors were associated with executive
      difficulties only in boys. CONCLUSION: The K-CPT may prove to be a useful
      indicator for early onset of executive control difficulties in preschool-aged
      children.

PMID- 25846229
TI  - The Prevalence and Comorbidity Rates of ADHD Among School-Age Children in Turkey.
AB  - OBJECTIVE: The aim of the present study was to explore the prevalence and
      comorbidity rates of ADHD in a community sample of school-age children. METHOD:
      Participants were 1,508 children aged 6 to 14 years. Parents and teachers of each
      child completed the Turgay Diagnostic and Statistical Manual of Mental Disorders
      (4th ed.; DSM-IV) Disruptive Behavior Disorders Rating Scale (T-DSM-IV-S). Screen
      positive cases were interviewed using the Schedule for Affective Disorders and
      Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL).
      Diagnoses were based on DSM-IV criteria. RESULTS: The prevalence rate of ADHD was
      8%. Children from extended families had extremely high rates (46.4%) of ADHD.
      Sixty percent of children with ADHD had one or more comorbid diagnoses. The most
      common comorbidities were learning disorders (35.7%) and oppositional defiant
      disorder (22.6%). CONCLUSION: The prevalence and comorbidity rates of ADHD in
      school-age children in Turkey are similar to those found in previous studies in
      other countries.

PMID- 25846230
TI  - The tolerance of the human body to automobile collision impact - a systematic
      review of injury biomechanics research, 1990-2009.
AB  - Road traffic injuries account for 1.3 million deaths per year world-wide.
      Mitigating both fatalities and injuries requires a detailed understanding of the
      tolerance of the human body to external load. To identify research priorities, it
      is necessary to periodically compare trends in injury tolerance research to the
      characteristics of injuries occurring in the field. This study sought to perform
      a systematic review on the last twenty years of experimental injury tolerance
      research, and to evaluate those results relative to available epidemiologic data.
      Four hundred and eight experimental injury tolerance studies from 1990-2009 were
      identified from a reference index of over 68,000 papers. Examined variables
      included the body regions, ages, and genders studied; and the experimental models
      used. Most (20%) of the publications studied injury to the spine. There has also
      been a substantial volume of biomechanical research focused on upper and lower
      extremity injury, thoracic injury, and injury to the elderly - although these
      injury types still occur with regularity in the field. In contrast, information
      on pediatric injury and physiological injury (especially in the central nervous
      system) remains lacking. Given their frequency of injury in the field, future
      efforts should also include improving our understanding of tolerances and
      protection of vulnerable road users (e.g., motorcyclists, pedestrians). 

PMID- 25846231
TI  - Full Bayesian evaluation of the safety effects of reducing the posted speed limit
      in urban residential area.
AB  - Full Bayesian (FB) before-after evaluation is a newer approach than the empirical
      Bayesian (EB) evaluation in traffic safety research. While a number of earlier
      studies have conducted univariate and multivariate FB before-after safety
      evaluations and compared the results with the EB method, often contradictory
      conclusions have been drawn. To this end, the objectives of the current study
      were to (i) perform a before-after safety evaluation using both the univariate
      and multivariate FB methods in order to enhance our understanding of these
      methodologies, (ii) perform the EB evaluation and compare the results with those
      of the FB methods and (iii) apply the FB and EB methods to evaluate the safety
      effects of reducing the urban residential posted speed limit (PSL) for policy
      recommendation. In addition to three years of crash data for both the before and
      after periods, traffic volume, road geometry and other relevant data for both the
      treated and reference sites were collected and used. According to the model
      goodness-of-fit criteria, the current study found that the multivariate FB model
      for crash severities outperformed the univariate FB models. Moreover, in terms of
      statistical significance of the safety effects, the EB and FB methods led to
      opposite conclusions when the safety effects were relatively small with high
      standard deviation. Therefore, caution should be taken in drawing conclusions
      from the EB method. Based on the FB method, the PSL reduction was found effective
      in reducing crashes of all severities and thus is recommended for improving
      safety on urban residential collector roads. 

PMID- 25846232
TI  - Methodological guidelines for developing accident modification functions.
AB  - This paper proposes methodological guidelines for developing accident
      modification functions. An accident modification function is a mathematical
      function describing systematic variation in the effects of road safety measures.
      The paper describes ten guidelines. An example is given of how to use the
      guidelines. The importance of exploratory analysis and an iterative approach in
      developing accident modification functions is stressed. The example shows that
      strict compliance with all the guidelines may be difficult, but represents a
      level of stringency that should be strived for. Currently the main limitations in
      developing accident modification functions are the small number of good
      evaluation studies and the often huge variation in estimates of effect. It is
      therefore still not possible to develop accident modification functions for very
      many road safety measures. 

PMID- 25846233
TI  - Using Adobe Flash animations of electron transport chain to teach and learn
      biochemistry.
AB  - Teaching the subject of the electron transport chain is one of the most
      challenging aspects of the chemistry curriculum at the high school level. This
      article presents an educational program called "Electron Transport Chain" which
      consists of 14 visual animations including a biochemistry quiz. The program was
      created in the Adobe Flash CS3 Professional animation program and is designed for
      high school chemistry students. Our goal is to develop educational materials that
      facilitate the comprehension of this complex subject through dynamic animations
      which show the course of the electron transport chain and simultaneously explain
      its nature. We record the process of the electron transport chain, including
      connections with oxidative phosphorylation, in such a way as to minimize the
      occurrence of discrepancies in interpretation. The educational program was
      evaluated in high schools through the administration of a questionnaire, which
      contained 12 opened-ended items and which required participants to evaluate the
      graphics of the animations, chemical content, student preferences, and its
      suitability for high school biochemistry teaching.

PMID- 25846234
TI  - T-cell chronic lymphocytic leukemia or small-cell variant of T-cell
      prolymphocytic leukemia: a historical perspective and search for consensus.
AB  - There is a rich history behind the extinct entity 'T-cell chronic lymphocytic
      leukemia (T-CLL)' and the now-established replacement, small-cell variant of T
      cell prolymphocytic leukemia (T-PLL-sv). Herein, we review the history of the
      events, observations, and discussions that led to this replacement. We also
      provide a systematic analysis of all previously reported cases of T-PLL-sv as
      well as our four new additional cases. Despite the higher frequency of a normal
      karyotype and perhaps an overrepresented CD4(-) CD8(-) immunophenotype among
      these patients (compared to T-PLL in general) as well as bland morphology (that
      makes them superficially appear more similar to B-CLL), we argue that the current
      World Health Organization (WHO)-based classification as T-PLL-sv is adequate and
      should continue for the time being. Morphologically, T-PLL-sv represents
      approximately one-fifth of all T-PLL cases. However, morphology alone does not
      determine the clinical course and should not be the basis for clinical decision
      making and prognostication. We propose a clonal evolution model in which mature T
      cell leukemias classified in the past as T-CLL are perhaps T-PLL diagnosed early
      in the course of the disease. Future research using next-generation sequencing,
      comparative genomic hybridization, and molecular array studies, including serial
      analyses of individual cases over time, is needed to better identify this rarely
      diagnosed, inherently controversial form of T-cell leukemia. 

PMID- 25846235
TI  - A bioelectronic system for insulin release triggered by ketone body mimicking
      diabetic ketoacidosis in vitro.
AB  - A bioelectronic system composed of two modified electrodes, one activated in the
      presence of ketone bodies, a biomarker of diabetic ketoacidosis, and another
      releasing insulin upon receiving a signal, was designed and tested in vitro to
      operate as a Sense-and-Act device. The functional integration of biomarker
      sensing and insulin-releasing electrodes represents a step to a theranostic
      system with autonomous operation. 

PMID- 25846236
TI  - A Non-Invasive NMR Method Based on Histidine Imidazoles to Analyze the pH
      Modulation of Protein-Nucleic Acid Interfaces.
AB  - A useful (2) J(N-H) coupling-based NMR spectroscopic approach is proposed to
      unveil, at the molecular level, the contribution of the imidazole groups of
      histidines from RNA/DNA-binding proteins on the modulation of binding to nucleic
      acids by pH. Such protonation/deprotonation events have been monitored on the
      single His96 located at the second RNA/DNA recognition motif (RRM2) of T-cell
      intracellular antigen-1 (TIA-1) protein. The pKa values of the His96 ionizable
      groups were substantially higher in the complexes with short U-rich RNA and T
      rich DNA oligonucleotides than those of the isolated TIA-1 RRM2. Herein, the
      methodology applied to determine changes in pKa of histidine side chains upon
      DNA/RNA binding, gives valuable information to understand the pH effect on
      multidomain DNA/RNA-binding proteins that shuttle among different cellular
      compartments.

PMID- 25846242
TI  - Triple-quantum-filtered sodium imaging at 9.4 Tesla.
AB  - PURPOSE: Efficient acquisition of triple-quantum-filtered (TQF) sodium images at
      ultra-high field (UHF) strength. METHODS: A three-pulse preparation and a stack
      of double-spirals were used for the acquisition of TQF images at 9.4 Tesla. The
      flip angles of the TQ preparation were smoothly reduced toward the edge of k
      space along the partition-encoding direction. In doing so, the specific
      absorption rate could be reduced while preserving the maximal signal intensity
      for the partitions most relevant for image contrast in the center of k-space.
      Simulations, phantom and in vivo measurements were used to demonstrate the
      usefulness of the proposed method. RESULTS: A higher sensitivity (~ 20%) was
      achieved compared to the standard acquisition without flip angle apodization.
      Signals from free sodium ions were successfully suppressed irrespective of the
      amount of apodization used. B0 corrected TQF images with a nominal resolution of
      5 * 5 * 5 mm(3) and an acceptable signal-to-noise ratio could be acquired in vivo
      within 21 min. CONCLUSION: Conventional TQF in combination with flip angle
      apodization permits to exploit more efficiently the increased sensitivity
      available at 9.4T.

PMID- 25846243
TI  - Erratum to: surgical therapy of neuroendocrine neoplasm with hepatic metastasis:
      patient selection and prognosis.

PMID- 25846244
TI  - The inhibition the Tet(K) efflux pump of tetracycline resistant Staphylococcus
      epidermidis by essential oils from three Salvia species.
AB  - The inhibition of efflux pumps is an attractive and powerful response to the
      emergence of bacteria resistant to antibiotics. Essential oils (EOs) from Salvia
      fruticosa, Salvia officinalis and Salvia sclarea reduce the minimal inhibition
      concentration of tetracycline, decrease efflux of antibiotic and decrease the
      expression of tet(K) gene in tetracycline resistant clinical isolates of
      Staphylococcus epidermidis. In all the cases S. fruticosa was the best one. By
      using checkerboard and time-killing methods, we found synergistic interactions of
      EOs with tetracycline. SIGNIFICANCE AND IMPACT OF THE STUDY: Our data from
      molecular and functional analyses of inhibitory effect of Salvia's essential
      oils, namely from S. fruticosa, on Tet(K) pump of Staphylococcus epidermidis and
      from modulatory studies may be the starting point for consecutive study of
      pharmacokinetic and pharmacodynamic parameters and their perspective use in
      combination therapy. Combination of antibiotic with efflux pump inhibitor would
      be expected to re-establish susceptibility of the bacteria to antibiotics that
      became no longer effective due to bacterial resistance through the efflux pumps.
      The inhibition of an efflux pump can potentially improve the clinical efficacy of
      an antibiotic and simultaneously decrease the selection of resistant mutants.

PMID- 25846245
TI  - Repression of jasmonate signaling by a non-TIFY JAZ protein in Arabidopsis.
AB  - JAsmonate ZIM-domain (JAZ) proteins repress the activity of transcription factors
      that execute responses to the plant hormone jasmonoyl-L-isoleucine (JA-Ile). The
      ZIM protein domain recruits the co-repressors NINJA and TOPLESS to JAZ-bound
      transcription factors, and contains a highly conserved TIF[F/Y]XG motif that
      defines the larger family of TIFY proteins to which JAZs belong. Here, we report
      that diverse plant species contain genes encoding putative non-TIFY JAZ proteins,
      including a previously unrecognized JAZ repressor in Arabidopsis (JAZ13, encoded
      by At3g22275). JAZ13 is most closely related to JAZ8 and includes divergent EAR,
      TIFY/ZIM, and Jas motifs. Unlike JAZ8, however, JAZ13 contains a Ser-rich C
      terminal tail that is a site for phosphorylation. Overexpression of JAZ13
      resulted in reduced sensitivity to JA, attenuation of wound-induced expression of
      JA-response genes, and decreased resistance to insect herbivory. JAZ13 interacts
      with the bHLH transcription factor MYC2 and the co-repressor TOPLESS but,
      consistent with the absence of a TIFY motif, neither NINJA nor other JAZs.
      Analysis of single and higher-order T-DNA insertion jaz null mutants provided
      further evidence that JAZ13 is a repressor JA signaling. Our results demonstrate
      that proteins outside the TIFY family are functional JAZ repressors and further
      suggest that this expansion of the JAZ family allows fine-tuning of JA-mediated
      transcriptional responses. 

PMID- 25846246
TI  - miR-154 suppresses non-small cell lung cancer growth in vitro and in vivo.
AB  - miR-154 has been proven to act as a tumor suppressor in several types of tumors.
      However, its role in non-small cell lung cancer (NSCLC) remains unclear. Thus,
      the aim of this study was to investigate the effects of miR-154 on NSCLC
      tumorigenesis and development. Using real-time quantitative PCR (qRT-PCR), we
      analyzed expression of miR-154 at the transcriptional level in 40 NSCLC tumor
      tissues and matched adjacent normal tissues and the correlation with
      clinicopathological features of the patients. The miR-154 mimic was stably
      transfected into NSCLC A549 cells, and the effects of miR-154 on cancer cell
      proliferation, colony formation, cell cycle arrest, apoptosis, migration and
      invasion in vitro, and on the growth of in vivo xenografts were investigated. miR
      154 expression levels were significantly downregulated in the NSCLC compared to
      the corresponding non-cancerous lung tissues (P<0.05), and decreased miR-154
      expression was significantly associated with metastasis (P<0.001), larger tumor
      size (P<0.001) and advanced TNM stage (P<0.001). Furthermore, transfection of the
      miR-154 mimic into the NSCLC A549 cells was able to inhibit cell proliferation,
      colony formation, invasion and migration, and induce cell apoptosis and G0/G1
      cell cycle arrest. Enforced expression of miR-154 also suppressed the growth of
      cancer cell xenografts in vivo. These findings indicate that miR-154 may become a
      potential target for miR-based therapy of NSCLC.

PMID- 25846247
TI  - Circumferential type A aortic dissection with intimal intussusception.
AB  - A 62-year-old man was admitted to our hospital with sudden chest pain. CT
      examination showed the presence of an intimal flap in the aortic root and in the
      descending aorta, with no intimal flap in the ascending aorta and curvilinear
      filling defects in the aortic arch, and extension into the left subclavian
      artery. Surgical treatment consisted of ascending aorta replacement. During the
      operation, the intimal tear was found to be circumferential with intussusception
      of the intimal layer. The patient died at surgery. 

PMID- 25846248
TI  - Potential for coronary CT angiography to tailor medical therapy beyond preventive
      guideline-based recommendations: insights from the ROMICAT I trial.
AB  - BACKGROUND: Coronary CT angiography (CCTA) is used in the emergency department to
      rule out acute coronary syndrome in low-intermediate risk patients. OBJECTIVES:
      We evaluated the potential of CCTA to tailor aspirin (ASA) and statin therapy in
      acute chest pain patients. METHODS: We included all patients in the ROMICAT I
      trial who underwent CCTA before admission. Results of CCTA were blinded to
      caretakers. We documented ASA and statin therapy at admission and discharge and
      determined change in medications during hospitalization, agreement of discharge
      medications with contemporaneous guidelines, and agreement with the presence and
      severity of coronary artery disease (CAD) as determined by CCTA. RESULTS: We
      included 368 patients (53 +/- 12 years; 61% male). Baseline medical therapy at
      presentation included 27% on ASA and 24% on statin. Most patients who qualified
      for secondary prevention were on ASA and statin therapy at discharge (95% and
      80%, respectively), whereas among those qualifying for primary prevention
      therapy, only 59% of patients were on aspirin and 33% were on statin at
      discharge. Excluding secondary prevention patients, among those with CCTA
      detected CAD, only 66/131 (50%) were on ASA at discharge and only 53/131 (40%)
      were on statin. Conversely, in those without CCTA-detected CAD, 54/156 (35%) were
      on ASA and 20/151 (13%) were on statin at discharge. CONCLUSION: There are
      significant discrepancies between discharge prescription of statin and ASA with
      the presence and extent of CAD. CCTA presents an efficient opportunity to tailor
      medical therapy to CAD in patients undergoing CCTA as part of their acute chest
      pain evaluation.

PMID- 25846249
TI  - beta-Blocker premedication does not increase the frequency of allergic reactions
      from coronary CT angiography: Results from the Advanced Cardiovascular Imaging
      Consortium.
AB  - BACKGROUND: beta-Blockers are often used for heart rate control during coronary
      CT angiography (CTA). Increased frequency and severity of allergic reactions to
      radiocontrast media (RCM) have been reported with concomitant use of beta
      blockers. OBJECTIVES: The objectives of this study were to determine whether
      there is a higher incidence of allergic reactions to low-osmolar nonionic RCM in
      patients undergoing coronary CTA with concomitant beta-blockers and to define the
      overall incidence and severity of allergic reactions in patients undergoing
      coronary CTA with and without a history of allergy to RCM. METHODS: Patients
      undergoing coronary CTA at 47 institutions participating in the Advanced
      Cardiovascular Imaging Consortium registry were analyzed. The incidence and
      severity of allergic reactions were compared between those patients who did and
      those who did not receive beta-blockers, as well as in subgroups of patients with
      and without a history of prior allergy to RCM. RESULTS: The incidence of allergic
      reaction in patients who received beta-blockers was 45 of 23,867 (0.19%) compared
      with those who did not receive beta-blockers, which was 9 of 5232 (0.17%; P =
      .84; odds ratio = 1.1). Of the patients with history of allergy to RCM, 4 of 706
      patients (0.6%) on beta-blockers experienced allergic reactions compared to 1 of
      77 patients (1.3%) without beta-blockers (P = .40; odds ratio = 0.43).
      CONCLUSIONS: beta-Blocker pretreatment had no effect on the frequency or severity
      of allergic reaction in patients undergoing coronary CTA, even in patients with a
      past history of allergy to RCM.

PMID- 25846252
TI  - Integration of the catalytic subunit activates deneddylase activity in vivo as
      final step in fungal COP9 signalosome assembly.
AB  - The eight-subunit COP9 signalosome (CSN) is conserved from filamentous fungi to
      humans and functions at the interface between cellular signalling and protein
      half-life control. CSN consists of six PCI and two MPN domain proteins and forms
      a scaffold for additional interacting proteins. CSN controls protein stability in
      the ubiquitin-proteasome system where the MPN domain CSN5/CsnE subunit
      inactivates cullin-RING ligases. The CSN5/CsnE isopeptidase functions as
      deneddylase and removes the ubiquitin-like protein Nedd8. The six PCI domain
      proteins of human CSN form a horseshoe-like ring and all eight subunits are
      connected by a bundle of C-terminal alpha-helices. We show that single deletions
      of any csn subunit of Aspergillus nidulans resulted in the lack of deneddylase
      activity and identical defects in the coordination of development and secondary
      metabolism. The CSN1/CsnA N-terminus is dispensable for deneddylase activity but
      required for asexual spore formation. Complex analyses in mutant strains revealed
      the presence of a seven-subunit pre-CSN without catalytic activity.
      Reconstitution experiments with crude extracts of deletion strains and
      recombinant proteins allowed the integration of CSN5/CsnE into pre-CSN resulting
      in an active deneddylase. This supports a stable seven subunit pre-CSN
      intermediate where deneddylase activation in vivo can be controlled by CSN5/CsnE
      integration as final assembly step. 

PMID- 25846251
TI  - A randomized controlled trial of treatments for co-occurring substance use
      disorders and post-traumatic stress disorder.
AB  - BACKGROUND AND AIMS: Post-traumatic stress disorder (PTSD) is common among people
      with substance use disorders, and the comorbidity is associated with negative
      outcomes. We report on a randomized controlled trial comparing the effect of
      integrated cognitive-behavioral therapy (ICBT) plus standard care, individual
      addiction counseling plus standard care and standard care alone on substance use
      and PTSD symptoms. DESIGN: Three-group, multi-site randomized controlled trial.
      SETTING: Seven addiction treatment programs in Vermont and New Hampshire, USA.
      PARTICIPANTS/CASES: Recruitment took place between December 2010 and January
      2013. In this single-blind study, 221 participants were randomized to one of
      three conditions: ICBT plus standard care (SC) (n = 73), individual addiction
      counseling (IAC) plus SC (n = 75) or SC only (n = 73). One hundred and seventy
      two patients were assessed at 6-month follow-up (58 ICBT; 61 IAC; 53 SC).
      Intervention and comparators: ICBT is a manual-guided therapy focused on PTSD and
      substance use symptom reduction with three main components: patient education,
      mindful relaxation and flexible thinking. IAC is a manual-guided therapy focused
      exclusively on substance use and recovery with modules organized in a stage-based
      approach: treatment initiation, early abstinence, maintaining abstinence and
      recovery. SC are intensive out-patient program services that include 9-12 hours
      of face-to-face contact per week over 2-4 days of group and individual therapies
      plus medication management. MEASUREMENTS: Primary outcomes were PTSD severity and
      substance use severity at 6 months. Secondary outcomes were therapy retention.
      FINDINGS: PTSD symptoms reduced in all conditions with no difference between
      them. In analyses of covariance, ICBT produced more favorable outcomes on
      toxicology than IAC or SC [comparison with IAC, parameter estimate: 1.10;
      confidence interval (CI) = 0.17-2.04; comparison with SC, parameter estimate:
      1.13; CI = 0.18-2.08] and had a greater reduction in reported drug use than SC
      (parameter estimate: -9.92; CI = -18.14 to -1.70). ICBT patients had better
      therapy continuation versus IAC (P<0.001). There were no unexpected or study
      related adverse events. CONCLUSIONS: Integrated cognitive behavioral therapy may
      improve drug-related outcomes in post-traumatic stress disorder sufferers with
      substance use disorder more than drug-focused counseling, but probably not by
      reducing post-traumatic stress disorder symptoms to a greater extent.

PMID- 25846253
TI  - Platelet aggregation values in patients with cardiovascular risk factors are
      reduced by verbascoside treatment. A randomized study.
AB  - Verbascoside, a phenolic compound, showed several favorable biological
      activities, including an antiplatelet activity. No in vivo studies tested its
      efficacy and safety in subjects with cardiovascular (CV) factors. The aim of this
      randomized, single-center, double-blind, phase II study was to assess the
      efficacy and tolerability of verbascoside intake for the modulation of platelet
      aggregation (PA) values in subjects with cardiovascular (CV) risk factors. One
      hundred subjects with at least one CV risk factor (age >65 years, diabetes
      mellitus, hypertension, current cigarettes use, hyperlidemia, waist circumference
      >102 cm in male or >88 cm in female) were enrolled and randomly assigned to
      receive placebo or verbascoside 50mg or verbascoside 100mg. PA was measured at
      baseline and after 2 weeks of study drug assumption, with light transmittance
      aggregometry (arachidonic acid, AA, 1 MUM and adenosine diphosphate, ADP, 5 MUM).
      Two weeks of treatment with placebo or verbascoside 50mg did not modify PA values
      (both after AA and ADP stimuli). On the contrary, after 2 weeks of verbascoside
      100mg, PA values decreased significantly (from 51 +/- 13% to 39 +/- 15%, p<0.01
      after AA; from 60 +/- 12% to 49 +/- 15%, p = 0.01 after ADP). No serious adverse
      events were reported during the study, and no subjects discontinued the study
      because of adverse events. We conclude that long-term intake of verbascoside
      100mg significantly reduces PA values in subjects with CV risk factors.

PMID- 25846254
TI  - Clinical evaluation of an improved cementation technique for implant-supported
      restorations: a randomized controlled trial.
AB  - BACKGROUND: Cement remnants were frequently associated with peri-implantitis.
      Recently, a shoulderless abutment was proposed, raising some concern about cement
      excess removal. AIM: To compare different cementation techniques for implant
      supported restorations assessing the amount of cement remnants in the peri
      implant sulcus. Additional aim was to compare the effect of these cementation
      techniques using two different abutment designs. MATERIAL & METHODS: Forty-six
      patients requiring double implant-supported restoration in the posterior maxilla
      were randomly divided in two groups according to the cementation modality:
      intraoral and extraoral. According to the abutment finishing line, implants in
      each patient were randomly assigned to shoulderless or chamfer subgroup. In the
      intraoral group, crowns were directly seated onto the titanium abutment. In the
      extraoral group, crowns were firstly seated onto a resin abutment replica and
      immediately removed, then cleansed of the cement excess and finally seated on the
      titanium abutment. After cement setting, in both groups, cement excess was
      carefully tried to remove. Three months later, framework/abutment complexes were
      disconnected and prepared for microscopic analysis: surface occupied by exposed
      cement remnants and marginal gaps were measured. Additionally, crown/abutment
      complexes were grinded, and voids of cement were measured at abutment/crown
      interface. Related-samples Friedman's two-way analysis of variance by ranks was
      used to detect differences between groups and subgroups (P <= 0.5). RESULTS: At
      the end of the study, a mean value of 0.45 mm2 (+/-0.80), 0.38 mm2 (+/-0.84), and
      0.065 mm2 (+/-0.13) and 0.07 mm2 (+/-0.15) described surface occupied by cement
      remnants in shoulderless and chamfer abutment with intraoral cementation and
      shoulderless and chamfer abutment with extraoral cementation, respectively. A
      mean value of 0.40 mm2 (+/-0.377), 0.41 mm2 (+/-0.39) and 0.485 mm2 (+/-0.47) and
      0.477 mm2 (+/-0.43) described cement voids at the abutment/crown interface; a
      mean value of 0.062 mm (+/-0.03), 0.064 mm (+/-0.35), 0.055 mm (+/-0.016) and
      0.054 mm (+/-0.024) described marginal gaps. Statistics showed tendency of
      intraoral cementation to have significantly higher cement remnants compared with
      abutments with extraoral cementation groups. At the same time, the presence of
      voids was significantly higher in case of extraoral cementation. No significant
      differences between groups for the variable "gap". CONCLUSIONS: Despite the
      presence of more voids, extraoral cementation reduces cement excess. However,
      using low adhesivity cement and careful cement removal, a very limited quantity
      of cement remnants was observed also in the intraoral cementation.

PMID- 25846250
TI  - Biomaterials for Bone Regenerative Engineering.
AB  - Strategies for bone tissue regeneration have been continuously evolving for the
      last 25 years since the introduction of the "tissue engineering" concept. The
      convergence of the life, physical, and engineering sciences has brought in
      several advanced technologies available to tissue engineers and scientists. This
      resulted in the creation of a new multidisciplinary field termed as "regenerative
      engineering". In this article, the role of biomaterials in bone regenerative
      engineering is systematically reviewed to elucidate the new design criteria for
      the next generation of biomaterials for bone regenerative engineering. The
      exemplary design of biomaterials harnessing various materials characteristics
      towards successful bone defect repair and regeneration is highlighted. Particular
      attention is given to the attempts of incorporating advanced materials science,
      stem cell technologies, and developmental biology into biomaterials design to
      engineer and develop the next generation bone grafts. 

PMID- 25846255
TI  - Utility of CMR Markers of Myocardial Injury in Predicting LV Functional Recovery:
      Results from PROTECTION AMI CMR Sub-study.
AB  - BACKGROUND: Adverse left ventricular (LV) remodelling following acute ST-segment
      elevation myocardial infarction (STEMI) has prognostic importance. We aimed to
      predict 90-day left ventricular (LV) function following acute STEMI using
      variables from clinical presentation, biomarkers, and cardiovascular magnetic
      resonance imaging (CMR). METHODS: Consecutive patients undergoing primary
      percutaneous coronary intervention for anterior STEMI as part of the Selective
      Inhibition of Delta-protein Kinase C for the Reduction of Infarct Size in Acute
      Myocardial Infarction (PROTECTION-AMI) trial were enrolled into the CMR sub-study
      at selected sites. CMR was performed at baseline (days 3 to 5) and 90 days and
      used to evaluate infarct size, myocardial salvage index, infarct heterogeneity,
      microvascular obstruction and global LV function. Biochemical markers including
      creatinine kinase area under the curve (CK AUC), peak CK, peak CK-myocardial band
      (CK-MB) and AUC, and troponin I were collected at specific time-points. RESULTS:
      Ninety-six patients were enrolled in the CMR sub study and 85 completed the 90
      day follow-up, across 24 centres worldwide. LV ejection fraction (EF) was 56% (46
      63%) at baseline and 60% (49-67%) at 90 days (p<0.001). Infarct size had moderate
      inverse correlation with 90-day EF (Spearman's rho=-0.7, p < 0.001) and had the
      strongest correlation when compared to myocardial salvage index (Spearman's
      rho=0.5, p=0.001), infarct heterogeneity (Spearman's rho=-0.4, p=0.02 or
      microvascular obstruction (Spearman's rho=-0.4, p<0.001). All biochemical markers
      had similar moderate relationship to LVEF at 90 days (Spearman's rho -0.6 to 
      0.8, p=0.001). In a multivariable model, only baseline LVEF, CMR infarct size and
      infarct heterogeneity independently predicted 90-day LVEF. CONCLUSION: This study
      reports findings of a combined CMR protocol (including myocardial oedema imaging)
      in a multi-centre, multi-vendor setting. We found infarct size, infarct
      heterogeneity and myocardial salvage index correlated favourably with 90-day
      LVEF, however only the former two were independently predictive.

PMID- 25846256
TI  - Incorporation of dried blood alpha fetoprotein into traditional first trimester
      Down syndrome screening service.
AB  - OBJECTIVE: The aim of this study was to determine whether incorporation of dried
      blood alpha fetoprotein (AFP) into first trimester screening using the
      biochemical markers free Beta human chorionic gonadotropin (hCG) and pregnancy
      associated plasma protein A (PAPP-A) can improve screening performance. METHODS:
      A retrospective study of 34 Down syndrome and 1185 unaffected dried blood
      specimens. First trimester dried blood AFP was performed using in-house
      immunofluorometric time-resolved assay. False positive and detection rates were
      determined from modeling. RESULTS: The multiple of the median in Down syndrome
      cases was 0.73. At a fixed 5% false positive rate, incorporating AFP into a free
      Beta hCG, PAPP-A, and nuchal translucency protocol adds 2% detection resulting in
      detection rates of 92% to 94% depending on the gestational age of the blood draw.
      At a fixed 90% detection rate, AFP reduced the false positive rate by 1.0 to 1.6
      percentage points depending on gestational age. Using a cutoff of 1/1000, the
      combination of free beta hCG, PAPP-A, AFP, and nuchal translucency achieved a
      detection rate of 96% with a false positive rate of 8.4% to 9.9%. Adding in nasal
      bone increased detection to 98% while reducing false positive rates to 4.1% to
      4.7%. CONCLUSION: Inclusion of dried blood AFP into traditional first trimester
      screening improves detection while optimizing contingent protocols so that cell
      free fetal DNA testing may be offered in a more cost effective manner.

PMID- 25846257
TI  - Bismuth-lithium bonding in the ion pairs: LiBiL2, where L = a porphyrin or a
      salen ligand.
AB  - From the reaction between BiCl3 (1 equiv.) and LiN(SiMe3)2 (4 equiv.) and LH2 (2
      equiv.), where L = a tetraphenylporphyrin, TPP, an octaethylporphyrin, OEP and
      phsalen in THF the title compounds have been obtained LiBiTPP2, LiBiOEP2, and
      LiBi(phsalen)2 and LiBi(phsalen)2.THF. Crystals grown from CH2Cl2-hexanes are
      colored; (green), (red-purple) and and (red-orange). The molecular structures of
      compound , and were determined by single-crystal X-ray crystallography and are
      shown to have short LiBi bonds of distance 2.8 A involving the LiL(-)BiL(+).
      Compound shows a slipped structure involving Li to two oxygens and a LiBi
      distance of 3.1 A. Compounds and undergo a rapid reversible exchange in toluene
      d8 at 90  degrees C. The MALDI-MS yields weak molecular ions due to LiBiL2(+/-)
      with more intense ions due to BiL(+) and LiL(-) in the positive and negative
      modes. The short Li(+) to Bi(3+) distances are comparable to those seen in LiBi
      compounds, such a LiBiR2, and are comparable to those seen by Pyykko (P. Pyykko,
      J. Phys. Chem. A, 2015, 119, 2326; P. Pyykko and M. Atsumi, Chem. - Eur. J.,
      2009, 15, 186; P. Pyykko and M. Atsumi, Chem. - Eur. J., 2009, 15, 12770) for Li
      Bi bonds. These can be seen to be involving Bi6s6p hybrid lone-pairs to Li(+)
      atoms. The lithium bis(bistrimethylsilyl)amide (2 equiv.) and phsalenH2 in THF
      gave a compound having Li2L.2THF, . Crystallographically compound contains two
      Li(+) atoms, one coordinated to five atoms LiO2N2.THF. and the other being
      coordinated to three atoms, LiO2.THF. By (7)Li and (1)H NMR both lithium atoms
      share an equivalent environment. 

PMID- 25846258
TI  - Fabrication and Characterization of Gd-DTPA-Loaded Chitosan-Poly(Acrylic Acid)
      Nanoparticles for Magnetic Resonance Imaging.
AB  - Gd-DTPA-loaded chitosan-poly(acrylic acid) nanoparticles (Gd-DTPA@CS-PAA NPs)
      were formulated based on the reaction system of water-soluble polymer-monomer
      pairs of acrylic acid in chitosan solution followed by sorption of Gd-DTPA.
      Morphological investigations revealed the spherical shape of these NPs with about
      220 nm particle size. These NPs showed charge reversal characteristic in acidic
      solution. In vitro and in vivo magnetic characteristics of these NPs were
      explored to estimate their utilization in targeted enhanced magnetic resonance
      imaging. Relaxation studies showed that these NPs possessed pH susceptible
      relaxation properties, which could introduce in vivo-specific distribution of
      contrast agent. MRI experiment showed that these nanoparticles had better results
      in contrast enhancement, and the concentration of contrast agent increased in
      liver and brain with increment in time. Thus, these NPs could maintain in vivo
      long circulation and high relaxation rate and were suitable agents for magnetic
      resonance imaging.

PMID- 25846259
TI  - In ovo L-arginine supplementation stimulates myoblast differentiation but
      negatively affects muscle development of broiler chicken after hatching.
AB  - In this study, we tested the hypothesis that in ovo feeding (IOF) of L-arginine
      (L-Arg) enhances nitric oxide (NO) production, stimulates the process of
      myogenesis, and regulates post-hatching muscle growth. Different doses of L-Arg
      were injected into the amnion of chicken embryos at embryonic day (ED) 16. After
      hatching, the body weight of individual male chickens was recorded weekly for 3
      weeks. During in vitro experiments, myoblasts of the pectoralis major (PM) were
      extracted at ED16 and were incubated in medium containing 0.01 mm L-Arg, 0.05 mm
      L-Arg, and (or) 0.05 mm L-nitro-arginine-methyl-ester (L-NAME), an inhibitor of
      nitric oxide synthase (NOS). When 25 mg/kg L-Arg/initial egg weight was injected,
      no difference was observed in body weight at hatch, but a significant decrease
      was found during the following 3 weeks compared to that of the non-injected and
      saline-injected control, and this also affected the growth of muscle mass. L-NAME
      inhibited gene expression of myogenic differentiation antigen (MyoD), myogenin,
      NOS, and follistatin, decreased the cell viability, and increased myostatin
      (MSTN) gene expression. 0.05 mm L-Arg stimulated myogenin gene expression but
      also depressed muscle cell viability. L-NAME blocked the effect of 0.05 mm L-Arg
      on myogenin mRNA levels when co-incubated with 0.05 mm L-Arg. L-Arg treatments
      had no significant influence on NOS mRNA gene expression, but had inhibiting
      effect on follistatin gene expression, while L-NAME treatments had effects on
      both. These results suggested that L-Arg stimulated myoblast differentiation, but
      the limited number of myoblasts would form less myotubes and then less myofibers,
      while the latter limited the growth of muscle mass.

PMID- 25846260
TI  - Identification of alkylated phosphates by gas chromatography-mass spectrometric
      investigations with different ionization principles of a thermally aged
      commercial lithium ion battery electrolyte.
AB  - The thermal aging process of a commercial LiPF6 based lithium ion battery
      electrolyte has been investigated in view of the formation of volatile phosphorus
      containing degradation products. Aging products were analyzed by GC-MS. Structure
      determination of the products was performed by support of chemical ionization MS
      in positive and negative modes. A fraction of the discovered compounds belongs to
      the group of fluorophosphates (phosphorofluoridates) which are in suspect of
      potential toxicity. This is well known for relative derivatives, e.g. diisopropyl
      fluorophosphate. Another fraction of the identified compounds belongs to the
      group of trialkyl phosphates. These compounds may provide a positive impact on
      the thermal and electrochemical performance of Li-based batteries as repeatedly
      described in the literature. 

PMID- 25846261
TI  - Simultaneous determination of polar and apolar compounds in environmental samples
      by a polyaniline/hydroxyl multi-walled carbon nanotubes composite-coated stir bar
      sorptive extraction coupled with high performance liquid chromatography.
AB  - Developing novel coatings for stir bar sorptive extraction (SBSE) is essential
      for extending the application of SBSE. Herein, a polyaniline/hydroxyl multi
      walled carbon nanotubes (PANi/MWCNTs-OH) composite-coated stir bar was prepared
      via the adhesion technique for the simultaneous extraction of polar and apolar
      compounds, and a novel method of PANi/MWCNTs-OH-coated SBSE coupled with high
      performance liquid chromatography-ultraviolet detection (HPLC-UV) was proposed.
      To test the extraction performance of PANi/MWCNTs-OH-coated stir bar, phenols,
      non-steroidal anti-inflammatory drugs, and polychlorinated biphenyls were
      selected as representatives for polar, semi-polar and apolar compounds,
      respectively. High enrichment factors (EFs) ranged from 20.4 to 60.4-fold
      (theoretical EF, 100-fold) for target analytes were achieved, indicating that the
      proposed method is applicable in simultaneous analysis of the compounds with
      different polarities. The prepared PANi/MWCNTs-OH-coated stir bar has a good
      preparation reproducibility and can be reused for 20 times. The limits of
      detection (LODs, S/N=3) were found to be in the range of 0.09-0.81MUg/L. To
      validate the applicability, the proposed method was successfully applied to the
      analysis of eight target analytes in Yangtze River water after filtration and in
      the extract from sediment samples. 

PMID- 25846262
TI  - Determination of the cardiac drug amiodarone and its N-desethyl metabolite in
      sludge samples.
AB  - For the first time, a procedure for the simultaneous determination of the
      iodinated drug amiodarone and its major metabolite, N-desethylamiodarone, in
      sludge from urban sewage treatment plants (STPs) is proposed. Matrix solid-phase
      dispersion (MSPD) followed by on-line cationic exchange clean-up, in modular
      configuration, was used as sample preparation technique. Liquid chromatography
      with tandem mass spectrometry (LC-MS/MS), based on a hybrid quadrupole time-of
      flight (QTOF) system, was employed for the selective determination of target
      compounds. The optimized procedure provided exhaustive recoveries with little
      effect of the sample matrix in the efficiency of electrospray ionization (ESI).
      The overall recoveries of the method ranged between 95 and 111%, for samples
      spiked at different concentration levels. The achieved limits of quantification
      (LOQs) remained below 10ngg(-1) for both compounds, and the linear response range
      extended up to 2500ngg(-1). Amiodarone and N-desethylamiodarone were ubiquitous
      in sludge samples, from different STPs located in the Northwest of Spain, with
      maximum concentrations above 300ngg(-1) referred to the freeze-dried matrix. They
      were also present in stabilized sludge (mixed with lime and thermally
      dehydrated), which is mostly disposed in agriculture fields as fertilizer.
      Furthermore, mono-iodinated analogues of amiodarone and N-desethylamiodarone were
      also tentatively identified in some samples from their accurate MS and MS/MS
      spectra. 

PMID- 25846263
TI  - High-performance thin-layer chromatography linked with (bio)assays and mass
      spectrometry - a suited method for discovery and quantification of bioactive
      components? Exemplarily shown for turmeric and milk thistle extracts.
AB  - Extraction parameters, chemical fingerprint, and the single compounds' activity
      levels were considered for the selection of active botanicals. For an initial
      survey, the total bioactivity (i.e., total reducing capacity, total flavonoids
      contents and free radical scavenging capacity) of 21 aqueous and 21 ethanolic
      plant extracts was investigated. Ethanolic extracts showed a higher yield and
      were further analyzed by HPTLC in detail to obtain fingerprints of single
      flavonoids and further bioactive components. Exemplarily shown for turmeric
      (Curcuma longa) and milk thistle (Silybum marianum), effect-directed analysis
      (EDA) was performed using three selected (bio)assays, the Aliivibrio fischeri
      bioassay, the Bacillus subtilis bioassay and the 2,2-diphenyl-1-picrylhydrazyl
      (DPPH*) assay. As a proof of principle, the bioactive components found in the
      extracts were confirmed by HPTLC-MS. Bioassays in combination with planar
      chromatography directly linked to the known, single effective compounds like
      curcumin and silibinin. However, also some unknown bioactive components were
      discovered and exemplarily characterized, which demonstrated the strength of this
      kind of EDA. HPTLC-UV/Vis/FLD-EDA-MS could become a useful tool for selection of
      active botanicals and for the activity profiling of the active ingredients
      therein. The flexibility in effect-directed detections allows a comprehensive
      survey of effective ingredients in samples. This streamlined methodology
      comprised a non-targeted, effect-directed screening first, followed by a highly
      targeted characterization of the discovered bioactive compounds. HPTLC-EDA-MS can
      also be recommended for bioactivity profiling of food on the food intake side, as
      not only effective phytochemicals, but also unknown bioactive degradation
      products during food processing or contamination products or residues or
      metabolites can be detected. Thus, an efficient survey on potential food intake
      effects on wellness could be obtained. Having performed both, sum parameter
      assays and HPTLC analysis, a comparison of both approaches was made and
      discussed. 

PMID- 25846265
TI  - Mechanical and chemical characterisation of demineralised human dentine after
      amalgam restorations.
AB  - OBJECTIVES: The purpose of this study was to evaluate the ability of Zn-free vs
      Zn-containing amalgams to induce remineralisation at the dentine interface.
      METHODOLOGY: Sound and caries-affected dentine surfaces (CAD) were subjected to
      both Zn-free and Zn-containing dental amalgam restorations. Dentine surfaces were
      studied by nano-indentation, Raman spectroscopy/cluster analysis, X-ray
      diffraction (XRD), field emission electron microscope (FESEM) and energy
      dispersive analysis (EDX), for mechanical, morphological and chemical
      characterisation. Analyses were performed before and after placement amalgam
      restorations. RESULTS: Zn-containing amalgams restorations promoted an increase
      in the nano-mechanical properties of sound and CAD surfaces. In samples from
      sound or CAD restored with Zn-containing amalgams, it was evidenced: (a) new
      mineral calcium-phosphate deposits (intratubular and intertubular) with augmented
      crystallographic maturity; these crystals were identified as hydroxyl-apatite,
      and (b) a generalised crosslinking reduction plus an increase in those values
      testing nature and secondary structure of collagen. It indicates an optimal
      preservation, molecular organisation and orientation of collagen fibrils.
      SIGNIFICANCE: Zn-containing amalgams promote remineralisation of subjacent
      dentine, which is more evident in caries affected dentine surfaces.

PMID- 25846264
TI  - Efficacy of P188 on lapine meniscus preservation following blunt trauma.
AB  - Traumatic injury to the knee leads to the development of post-traumatic
      osteoarthritis. The objective of this study was to characterize the effects of a
      single intra-articular injection of a non-ionic surfactant, Poloxamer 188 (P188),
      in preservation of meniscal tissue following trauma through maintenance of
      meniscal glycosaminoglycan (GAG) content and mechanical properties. Flemish Giant
      rabbits were subjected to a closed knee joint, traumatic compressive impact with
      the joint constrained to prevent anterior tibial translation. The contralateral
      limb served as an un-impacted control. Six animals (treated) received an
      injection of P188 in phosphate buffered saline (PBS) post trauma, and another six
      animals (sham) received a single injection of PBS to the impacted limb.
      Histological analyses for GAG was determined 6 weeks post trauma, and functional
      outcomes were assessed using stress relaxation micro-indentation. The impacted
      limbs of the sham group demonstrated a significant decrease in meniscal GAG
      coverage compared to non-impacted limbs (p<0.05). GAG coverage of the impacted
      P188 treated limbs was not significantly different than contralateral non
      impacted limbs in all regions except the medial anterior (p<0.05). No significant
      changes were documented in mechanics for either the sham or treated groups
      compared to their respective control limbs. This suggests that a single intra
      articular injection of P188 shows promise in prevention of trauma induced GAG
      loss. 

PMID- 25846266
TI  - Deletion of chromosome 8q22.1, a critical region for Nablus mask-like facial
      syndrome: four additional cases support a role of genetic modifiers in the
      manifestation of the phenotype.

PMID- 25846267
TI  - Fibular motor nerve conduction studies: Investigating the mechanism for compound
      muscle action potential amplitude drop with proximal stimulation.
AB  - INTRODUCTION: The compound muscle action potential (CMAP) amplitude of extensor
      digitorum brevis can show a drop with proximal stimulation in normal fibular
      nerves. METHODS: We assessed the contribution of the far-field potential recorded
      by the reference electrode (R-CMAP) to the fibular CMAP. Negative R-CMAP
      amplitude, peak-to-peak amplitude, and negative area were measured and correlated
      with the amplitude decrease. Fibular motor nerves from 14 healthy participants
      were studied. RESULTS: The mean CMAP amplitude drop with proximal stimulation was
      14.0 +/- 9.3%, including a >30% reduction in 1 study. All measured R-CMAP
      parameters correlated with the degree of amplitude drop. CONCLUSIONS: A greater R
      CMAP contribution to the fibular CMAP leads to greater phase cancellation and
      temporal dispersion. The resulting amplitude drop seen in the proximal CMAP can
      be large enough to be classified incorrectly as "probable conduction block" by
      several different diagnostic criteria.

PMID- 25846269
TI  - Cluster coarsening on drops exhibits strong and sudden size-selectivity.
AB  - Autophagy, an important process for degradation of cellular components, requires
      the targeting of autophagy receptor proteins to potential substrates. Receptor
      proteins have been observed to form clusters on membranes. To understand how
      receptor clusters might affect autophagy selectivity, we model cluster coarsening
      on a polydisperse collection of spherical drop-like substrates. Our model
      receptor corresponds to NBR1, which supports peroxisome autophagy. We recover
      dynamical scaling of cluster sizes, but find that changing the drop size
      distribution changes the cluster-size scaling distribution. The magnitude of this
      effect is similar to how changing the spatial-dimension affects scaling in bulk
      systems. We also observe a sudden onset of size-selection of the remaining drops
      with clusters, due to clusters evaporating from smaller drops and growing on
      larger drops. This coarsening-driven size selection provides a physical mechanism
      for autophagy selectivity, and may explain reports of size selection during
      peroxisome degradation. 

PMID- 25846268
TI  - Standards of Evidence for Efficacy, Effectiveness, and Scale-up Research in
      Prevention Science: Next Generation.
AB  - A decade ago, the Society of Prevention Research (SPR) endorsed a set of
      standards for evidence related to research on prevention interventions. These
      standards (Flay et al., Prevention Science 6:151-175, 2005) were intended in part
      to increase consistency in reviews of prevention research that often generated
      disparate lists of effective interventions due to the application of different
      standards for what was considered to be necessary to demonstrate effectiveness.
      In 2013, SPR's Board of Directors decided that the field has progressed
      sufficiently to warrant a review and, if necessary, publication of "the next
      generation" of standards of evidence. The Board convened a committee to review
      and update the standards. This article reports on the results of this committee's
      deliberations, summarizing changes made to the earlier standards and explaining
      the rationale for each change. The SPR Board of Directors endorses "The Standards
      of Evidence for Efficacy, Effectiveness, and Scale-up Research in Prevention
      Science: Next Generation." 

PMID- 25846270
TI  - Rikkunshito induces gastric relaxation via the beta-adrenergic pathway in Suncus
      murinus.
AB  - BACKGROUND: Rikkunshito (RKT) is a gastroprotective herbal medicine. In this
      study, we investigated the role of RKT in the relaxation of the gastric body
      (fundus and corpus) and antrum. METHODS: We used Suncus murinus, a unique small
      model animal with similar gastrointestinal motility to humans and dogs. RKT was
      added at 0.1, 1.0, and 5.0 mg/mL to induce relaxation in vitro; the outcome
      measure was the intensity of relaxation. The number of spontaneous antral
      contractions in the absence or the presence of RKT was also counted. KEY RESULTS:
      Rikkunshito induced the relaxation of the gastric body and antrum and decreased
      the number of spontaneous antral contractions in a dose-dependent manner. The
      responses to RKT (1.0 mg/mL) were not affected by pretreatment with atropine, N
      nitro-l-arginine methyl ester, ritanserin, or ondansetron. On the other hand,
      timolol almost completely reversed the relaxation induced by RKT (1.0 mg/mL) on
      the gastric body and antrum and the occurrence of the spontaneous antral
      contractions. Both butoxamine, a beta(2) -adrenoreceptor antagonist, and L
      748337, a beta(3) -adrenoreceptor antagonist, but not CGP 20712, a beta(1) 
      adrenoreceptor antagonist, significantly reversed the RKT-induced (1.0 mg/mL)
      gastric relaxation. CONCLUSIONS & INFERENCES: These results indicate that RKT
      stimulates and modulates gastric relaxation through beta(2) - and beta(3) 
      adrenergic, but not beta(1) -adrenergic, pathways in S. murinus.

PMID- 25846271
TI  - RBRIdent: An algorithm for improved identification of RNA-binding residues in
      proteins from primary sequences.
AB  - Rapid and correct identification of RNA-binding residues based on the protein
      primary sequences is of great importance. In most prevalent machine-learning
      based identification methods; however, either some features are inefficiently
      represented, or the redundancy between features is not effectively removed. Both
      problems may weaken the performance of a classifier system and raise its
      computational complexity. Here, we addressed the above problems and developed a
      better classifier (RBRIdent) to identify the RNA-binding residues. In an
      independent benchmark test, RBRIdent achieved an accuracy of 76.79%, Matthews
      correlation coefficient of 0.3819 and F-measure of 75.58%, remarkably
      outperforming all prevalent methods. These results suggest the necessity of
      proper feature description and the essential role of feature selection in this
      project. All source data and codes are freely available at
      http://166.111.152.91/RBRIdent.

PMID- 25846272
TI  - Disulfiram/copper-disulfiram Damages Multiple Protein Degradation and Turnover
      Pathways and Cytotoxicity is Enhanced by Metformin in Oesophageal Squamous Cell
      Carcinoma Cell Lines.
AB  - Disulfiram (DSF), used since the 1950s in the treatment of alcoholism, is
      reductively activated to diethyldithiocarbamate and both compounds are thiol
      reactive and readily complex copper. More recently DSF and copper-DSF (Cu-DSF)
      have been found to exhibit potent anticancer activity. We have previously shown
      that the anti-diabetic drug metformin is anti-proliferative and induces an
      intracellular reducing environment in oesophageal squamous cell carcinoma (OSCC)
      cell lines. Based on these observations, we investigated the effects of Cu-DSF
      and DSF, with and without metformin, in this present study. We found that Cu-DSF
      and DSF caused considerable cytotoxicity across a panel of OSCC cells, and
      metformin significantly enhanced the effects of DSF. Elevated copper transport
      contributes to DSF and metformin-DSF-induced cytotoxicity since the cell
      impermeable copper chelator, bathocuproinedisulfonic acid, partially reversed the
      cytotoxic effects of these drugs, and interestingly, metformin-treated OSCC cells
      contained higher intracellular copper levels. Furthermore, DSF may target cancer
      cells preferentially due to their high dependence on protein degradation/turnover
      pathways, and we found that metformin further enhances the role of DSF as a
      proteasome inhibitor. We hypothesized that the lysosome could be an additional,
      novel, target of DSF. Indeed, this acid-labile compound decreased lysosomal
      acidification, and DSF-metformin co-treatment interfered with the progression of
      autophagy in these cells. In summary, this is the first such report identifying
      the lysosome as a target of DSF and based on the considerable cytotoxic effects
      of DSF either alone or in the presence of metformin, in vitro, and we propose
      these as novel potential chemotherapeutic approaches for OSCC.

PMID- 25846273
TI  - Predicting pathogen-specific CD8 T cell immune responses from a modeling
      approach.
AB  - The primary CD8 T cell immune response constitutes a major mechanism to fight an
      infection by intra-cellular pathogens. We aim at assessing whether pathogen
      specific dynamical parameters of the CD8 T cell response can be identified, based
      on measurements of CD8 T cell counts, using a modeling approach. We generated
      experimental data consisting in CD8 T cell counts kinetics during the response to
      three different live intra-cellular pathogens: two viruses (influenza, vaccinia)
      injected intranasally, and one bacteria (Listeria monocytogenes) injected
      intravenously. All pathogens harbor the same antigen (NP68), but differ in their
      interaction with the host. In parallel, we developed a mathematical model
      describing the evolution of CD8 T cell counts and pathogen amount during an
      immune response. This model is characterized by 9 parameters and includes
      relevant feedback controls. The model outputs were compared with the three data
      series and an exhaustive estimation of the parameter values was performed. By
      focusing on the ability of the model to fit experimental data and to produce a
      CD8 T cell population mainly composed of memory cells at the end of the response,
      critical parameters were identified. We show that a small number of parameters (2
      4) define the main features of the CD8 T cell immune response and are
      characteristic of a given pathogen. Among these parameters, two are related to
      the effector CD8 T cell mediated control of cell and pathogen death. The
      parameter associated with memory cell death is shown to play no relevant role
      during the main phases of the CD8 T cell response, yet it becomes essential when
      looking at the predictions of the model several months after the infection. 

PMID- 25846275
TI  - Cellular aggregate capture by fluidic manipulation device highly compatible with
      micro-well-plates.
AB  - This paper proposes a capture device to manipulate and transport a cellular
      aggregate in a micro-well. A cellular aggregate (a few hundreds MUm in diameter)
      is currently manipulated by a pipette. The manual manipulation by a pipette has
      problems; low reliability, low throughput, and difficulty in confirmation of task
      completion. We took into account of compatibility with existing methods such as a
      micro-well-plate and designed for the capture device of a cellular aggregate in a
      micro-well. A newly developed capture device flows and carries a cellular
      aggregate from a bottom of a well to a trap of the capture device. We designed a
      curved surface at the bottom of the capture device to form a space to act as a
      channel between the inner wall of the micro-well. This paper presents concept,
      design, fabrication, and of the proposed cellular aggregate capture, followed by
      successful experimental results. 

PMID- 25846274
TI  - Juxtamembrane contribution to transmembrane signaling.
AB  - Signaling across the cell membrane mediated by transmembrane receptors plays an
      important role in diverse biological processes. Recent studies have indicated
      that, in a number of single-span transmembrane receptors, the intracellular
      juxtamembrane (JM) sequence linking the transmembrane helix with the rest of the
      cytoplasmic domain participates directly in the signaling process via several
      novel mechanisms. This review briefly highlights several modes of JM dynamics in
      the context of signal transduction that are shared by different types of
      transmembrane receptors.

PMID- 25846276
TI  - Clinical utility estimation for assay cutoffs in early phase oncology enrichment
      trials.
AB  - Predictive enrichment strategies use biomarkers to selectively enroll oncology
      patients into clinical trials to more efficiently demonstrate therapeutic
      benefit. Because the enriched population differs from the patient population
      eligible for screening with the biomarker assay, there is potential for bias when
      estimating clinical utility for the screening eligible population if the
      selection process is ignored. We write estimators of clinical utility as
      integrals averaging regression model predictions over the conditional
      distribution of the biomarker scores defined by the assay cutoff and discuss the
      conditions under which consistent estimation can be achieved while accounting for
      some nuances that may arise as the biomarker assay progresses toward a companion
      diagnostic. We outline and implement a Bayesian approach in estimating these
      clinical utility measures and use simulations to illustrate performance and the
      potential biases when estimation naively ignores enrichment. Results suggest that
      the proposed integral representation of clinical utility in combination with
      Bayesian methods provide a practical strategy to facilitate cutoff decision
      making in this setting.

PMID- 25846278
TI  - Platelet endothelial cell adhesion molecule-1 gene 125C/G polymorphism is
      associated with deep vein thrombosis.
AB  - Deep vein thrombosis (DVT) is a common disorder that is associated with high
      morbidity and mortality. Genetic factors have been suggested to influence the
      predisposition towards thrombosis and the incidence of DVT. Platelet endothelial
      cell adhesion molecule-1 (PECAM-1) is a key adhesion molecule that is involved in
      platelet function and maintenance of endothelial cell junctions. To date, no
      studies have examined the association between polymorphisms in PECAM-1 and DVT.
      The present study analyzed the single nucleotide polymorphisms (SNPs) of PECAM-1,
      namely Leu125Val (C373G), Asn563Ser (T1688C) and Gly670Arg (C2008T), in Chinese
      patients with DVT and age-and gender-matched controls, using polymerase chain
      reaction-restriction fragment length polymorphism analysis. Furthermore, plasma
      soluble PECAM-1 (sPECAM-1) levels were quantified by ELISA. The results of the
      present study demonstrated significantly higher genotype and allele frequencies
      of the Leu125Val polymorphism in PECAM-1 in the DVT group as compared with those
      in the control group (P<0.05). The plasma levels of sPECAM-1 in the DVT group
      (83.4 +/- 23.5 ng/ml) were also significantly higher as compared with those in
      the control group (60.4 +/- 19.4 ng/ml, P<0.01). In the patients with DVT, plasma
      levels of sPECAM-1 were significantly higher in those with the Leu/Val and
      Val/Val genotypes as compared with those possessing the Leu/Leu genotype
      (P<0.05). The PECAM-1 Leu125Val polymorphism was shown to be associated with an
      increased risk of DVT and PECAM-1 protein expression levels in venous vessels. In
      patients with DVT, the PECAM-1 Leu/Val and Val/Val genotypes were associated with
      delayed thrombus resolution, as determined by thrombus scoring, as compared with
      that in patients possessing the Leu/Val genotype. In conclusion, the present
      study indicated that PECAM-1 Leu125Val polymorphism and sPECAM-1 levels may be
      associated with DVT.

PMID- 25846277
TI  - Downregulation of CRNN gene and genomic instability at 1q21.3 in oral squamous
      cell carcinoma.
AB  - OBJECTIVES: This study includes the direct sequencing of cornulin (CRNN) gene to
      elucidate the possible mechanism of CRNN downregulation and explore the genetic
      imbalances at 1q21.3 across oral squamous cell carcinoma (OSCC) samples.
      MATERIALS AND METHODS: In mutation screening of CRNN gene, gDNA from OSCC tissues
      were extracted, amplified, and followed by direct sequencing. OSCC samples were
      also subjected to fragment analysis on CRNN gene to investigate its
      microsatellite instability (MSI) and loss of heterozygosity (LOH).
      Immunohistochemistry was performed to validate CRNN downregulation in OSCC
      samples. RESULTS: No pathogenic mutation was found in CRNN gene, while high
      frequency of allelic imbalances was found at 1q21.3 region. MSI was found more
      frequent (25.3 %) than LOH (9.3 %). Approximately 22.6 % of cases had high MSI
      which reflects higher probability of inactivation of DNA mismatch repair genes.
      MSI showed significant association with no betel quid chewing (p = 0.003) and
      tongue subsite (p = 0.026). LOH was associated with ethnicity (p = 0.008) and
      advanced staging (p = 0.039). The LOH at 1q21.3 was identified to be as an
      independent prognostic marker in OSCC (HRR = 7.15 (95 % CI, 1.41-36.25), p =
      0.018). Downregulation of CRNN was found among MSI-positive OSCCs and was
      associated with poor prognosis (p = 0.044). CONCLUSION: This study showed a
      significant correlation between LOH/MSI at 1q21.3 with clinical outcomes and that
      downregulation of CRNN gene could be considered as a prognostic marker of OSCC.
      CLINICAL RELEVANCE: Insights of the downregulation mode of CRNN gene lays the
      basis of drug development on this gene as well as revealing its prognostic value.

PMID- 25846279
TI  - Reply.

PMID- 25846286
TI  - Candida arteritis in kidney transplant recipients: case report and review of the
      literature.
AB  - Multi-organ procurement is a risk factor for contamination of preservation fluid
      with intestinal flora including fungi (e.g., Candida). Transmission of fungal
      species to the graft vessel can cause mycotic arteritis. This is a very rare but
      life-threatening complication of renal transplantation. We present 2 cases of
      renal transplant recipients from the same multi-organ donor. Both recipients
      suffered from severe hemorrhages from renal graft anastomosis and renal artery
      pseudoaneurysm due to Candida albicans arteritis (CAA). The culture of the
      preservation fluid revealed growth of Escherichia coli, but neither preservation
      fluid nor multiple routine blood cultures performed before hemorrhagic
      complications revealed fungal growth (media non-selective for fungal growth were
      applied). The first recipient suffered from sudden severe hemorrhage in the area
      of graft anastomosis on day 10 post surgery (without any preceding clinical or
      radiological symptoms). This led to urgent surgery and graftectomy, which was
      complicated by cardio-respiratory arrest with resuscitation in the operating
      room; despite resuscitation, irreversible brain damage, and subsequent death
      occurred in the intensive care unit (ICU) 2 weeks later (on day 24 after
      transplantation). The second patient underwent urgent vascular surgery on day 22
      (after transplantation), because of hemorrhage from a pseudoaneurysm of the graft
      artery. She required repeated vascular operations, extended antimicrobial and
      antifungal therapy, and ICU monitoring and, despite these interventions, she died
      on day 80 after transplantation as a result of Pseudomonas aeruginosa sepsis.
      Arteritis of the renal artery in both patients was caused by C. albicans. This
      was confirmed by histopathology: infiltration of renal artery with budding yeast
      forming pseudohyphae (Case 1), and the presence of C. albicans in the culture of
      the renal artery and surrounding tissue (Case 2). We conclude that organ
      preservation solution should be cultured with use of media selective for fungal
      growth. As soon as the positive culture is detected, appropriate measures
      protecting patients against CAA should be undertaken.

PMID- 25846289
TI  - Getting it first versus getting it right: weighing the value of and evidence for
      progression-free survival as a surrogate endpoint for overall survival in
      glioblastoma.

PMID- 25846288
TI  - Unsanctifying the sanctuary: challenges and opportunities with brain metastases.
AB  - While the use of targeted therapies, particularly radiosurgery, has broadened
      therapeutic options for CNS metastases, patients respond minimally and prognosis
      remains poor. The inability of many systemic chemotherapeutic agents to penetrate
      the blood-brain barrier (BBB) has limited their use and allowed brain metastases
      to become a burgeoning clinical challenge. Adequate preclinical models that
      appropriately mimic the metastatic process, the BBB, and blood-tumor barriers
      (BTB) are needed to better evaluate therapies that have the ability to enhance
      delivery through or penetrate into these barriers and to understand the
      mechanisms of resistance to therapy. The heterogeneity among and within different
      solid tumors and subtypes of solid tumors further adds to the difficulties in
      determining the most appropriate treatment approaches and methods of laboratory
      and clinical studies. This review article discusses therapies focused on
      prevention and treatment of CNS metastases, particularly regarding the BBB, and
      the challenges and opportunities these therapies present. 

PMID- 25846291
TI  - Dengue seroprevalence in the French West Indies: a prospective study in adult
      blood donors.
AB  - Using an anti-dengue immunoglobulin G (IgG) indirect enzyme-linked immunosorbent
      assay, seroprevalence was determined among 783 adult blood donors in the French
      Caribbean islands of Guadeloupe and Martinique in 2011. Overall, 93.5% [91.5;
      95.1] samples were positive for dengue antibodies, 90.7% (350 of 386) in
      Martinique and 96.2% (382 of 397) in Guadeloupe. Only 30% of these adults
      recalled having had dengue disease before. Serotype-specific neutralization
      assays applied to a subset of IgG-positive samples indicated that a majority (77
      of 96; 80%) reacted to the four serotypes. These seroprevalence findings are the
      first reported for Guadeloupe and Martinique and are consistent with the dengue
      epidemiology in these territories. 

PMID- 25846292
TI  - Persistent strongyloidiasis complicated by recurrent meningitis in an HTLV
      seropositive Peruvian migrant resettled in Italy.
AB  - We describe a case of persistent strongyloidiasis complicated by recurrent
      meningitis, in a human T cell lymphotropic virus type 1 (HTLV-1) seropositive
      Peruvian migrant adult resettled in Italy. He was admitted with signs and
      symptoms of acute bacterial meningitis, reporting four other meningitis episodes
      in the past 6 years, with an etiological diagnosis of Escherichia coli and
      Enterococcus faecium in two cases. He had been previously treated with several
      antihelmintic regimens not including ivermectin, without eradication of
      strongyloidiasis, and he had never been tested for HTLV before. During the
      described episode, the patient was treated for meningitis with broad-spectrum
      antibiotic therapy and 200 MUg/kg/dose oral ivermectin once daily on day 1, 2, 15
      and 16 with full recovery and no further episodes of meningitis. The presented
      case underlines several critical points concerning the management of poorly known
      neglected diseases such as strongyloidiasis and HTLV infection in low-endemic
      areas. Despite several admissions for meningitis and strongyloidiasis, the
      parasitic infection was not adequately treated and the patient was not previously
      tested for HTLV. The supply of ivermectin and the choice of treatment scheme was
      challenging since ivermectin is not approved in Italy and there are no
      standardized guidelines for the treatment of severe strongyloidiasis in HTLV
      seropositive subjects. 

PMID- 25846294
TI  - The post-2015 development agenda: keeping our focus on the worst off.
AB  - Non-communicable diseases now account for the majority of the global burden of
      disease and an international campaign has emerged to raise their priority on the
      post-2015 development agenda. We argue, to the contrary, that there remain strong
      reasons to prioritize maternal and child health. Policy-makers ought to assign
      highest priority to the health conditions that afflict the worst off. In virtue
      of how little healthy life they have had, children who die young are among the
      globally worst off. Moreover, many interventions to deal with the conditions that
      cause mortality in the young are low-cost and provide great benefits to their
      recipients. Consistent with the original Millennium Development Goals, the
      international community should continue to prioritize reductions in communicable
      diseases, neonatal conditions, and maternal health despite the shifts in the
      global burden of disease. 

PMID- 25846293
TI  - Needs, acceptability, and value of humanitarian medical assistance in remote
      Peruvian Amazon riverine communities.
AB  - Much debate exists regarding the need, acceptability, and value of humanitarian
      medical assistance. We conducted a cross-sectional study on 457 children under 5
      years from four remote riverine communities in the Peruvian Amazon and collected
      anthropometric measures, blood samples (1-4 years), and stool samples. Focus
      groups and key informant interviews assessed perspectives regarding medical aid
      delivered by foreigners. The prevalence of stunting, anemia, and intestinal
      parasites was 20%, 37%, and 62%, respectively. Infection with multiple parasites,
      usually geohelminths, was detected in 41% of children. The prevalence of
      intestinal parasites both individual and polyparasitism increased with age.
      Participants from smaller communities less exposed to foreigners expressed lack
      of trust and fear of them. However, participants from all communities were
      positive about foreigners visiting to provide health support. Prevalent health
      needs such as parasitic infections and anemia may be addressed by short-term
      medical interventions. There is a perceived openness to and acceptability of
      medical assistance delivered by foreign personnel. 

PMID- 25846295
TI  - Trichinellosis in Vietnam.
AB  - Trichinellosis is a zoonotic parasitic disease with a worldwide distribution. The
      aim of this work was to describe the epidemiological and clinical data of five
      outbreaks of trichinellosis, which affected ethnic minorities living in remote
      mountainous areas of northwestern Vietnam from 1970 to 2012. Trichinellosis was
      diagnosed in 126 patients, of which 11 (8.7%) were hospitalized and 8 (6.3%)
      died. All infected people had consumed raw pork from backyard and roaming pigs or
      wild boar at wedding, funeral, or New Year parties. The short incubation period
      (average of 9.5 days), the severity of the symptoms, which were characterized by
      diarrhea, abdominal pain, fever, myalgia, edema, weight loss, itch, and lisping,
      and the high mortality, suggest that patients had ingested a high number of
      larvae. The larval burden in pigs examined in one of the outbreaks ranged from 70
      to 879 larvae/g. These larvae and those collected from a muscle biopsy taken from
      a patient from the 2012 outbreak were identified as Trichinella spiralis. Data
      presented in this work show that the northern regions of Vietnam are endemic
      areas for Trichinella infections in domestic pigs and humans. 

PMID- 25846296
TI  - 2013 dengue outbreaks in Singapore and Malaysia caused by different viral
      strains.
AB  - Characterization of 14,079 circulating dengue viruses in a cross-border
      surveillance program, UNITEDengue, revealed that the 2013 outbreaks in Singapore
      and Malaysia were associated with replacement of predominant serotype. While the
      predominant virus in Singapore switched from DENV2 to DENV1, DENV2 became
      predominant in neighboring Malaysia. Dominance of DENV2 was most evident on the
      southern states where higher fatality rates were observed. 

PMID- 25846297
TI  - Use of eCompliance, an innovative biometric system for monitoring of tuberculosis
      treatment in rural Uganda.
AB  - Directly observed therapy short-course (DOTS) requires direct observation of
      tuberculosis (TB) patients and manual recording of doses taken. Programmatically,
      manual tracking is both time-consuming and prone to human error. Our project in
      western Uganda assessed the impact on TB treatment outcomes of a comprehensive
      patient support program including eCompliance, a biometric medical record device,
      with the aim of increasing TB patient retention. Through an observational study
      of 142 patients, DOTS outcomes of patients in the intervention group were
      compared with two control groups. Descriptive statistical comparisons, case
      cohort analysis, and difference in change over time were used to assess the
      impact. Intervention patients had a higher cure rate than all other patients
      (55.6% versus 28.3% [P < 0.01]) and the odds of having a "cured" outcome were
      3.17 higher (P < 0.05). The intervention group had a statistically significantly
      lower odds of having a negative outcome (0% versus.17% [P < 0.01]) than patients
      from the control groups. Additionally, the intervention group had a lost to
      follow-up rate lower than all other groups (0% versus 7%) that was trending on
      significant. In resource-limited settings, implementing comprehensive DOTS
      including eCompliance may reduce the occurrence of negative DOTS outcomes for
      patients. 

PMID- 25846298
TI  - Determinants of societal costs in Alzheimer's disease: GERAS study baseline
      results.
AB  - BACKGROUND: To identify the main factors associated with societal costs of
      Alzheimer's disease (AD) in community-dwelling patients across three European
      countries. METHODS: Baseline cost data from a prospective, observational study
      were used. Assessments included patients' cognition, activities of daily living
      (ADLs) and behavioral symptoms, and caregiver burden. Cost calculations (2010)
      from the societal perspective were based on patient/caregiver resource use.
      Generalized linear models estimated factors associated with costs. RESULTS: Mean
      monthly costs per patient differed for France (?1881), Germany (?2349), and the
      UK (?2016), with informal care costs accounting for 50% to 61%. Independent
      factors associated with costs across all countries were ADL total score, patient
      living arrangements, caregiver working status, and caregiver burden (all P <
      .05). Additional factors were significant for the pooled cohort or individual
      countries. CONCLUSIONS: Several patient and caregiver factors, including factors
      associated with informal care, should be included when evaluating care options
      for patients with AD.

PMID- 25846300
TI  - In vivo processing and release into the circulation of GFP fusion protein in
      arginine vasopressin enhanced GFP transgenic rats: response to osmotic
      stimulation.
AB  - Arginine vasopressin (AVP) is a neurohypophysial hormone synthesized as a part of
      a prepropeptide precursor containing the signal peptide, AVP hormone, AVP
      associated neurophysin II and copeptin in the hypothalamic neurosecretory
      neurons. A transgenic (Tg) rat line expressing the AVP-eGFP fusion gene has been
      generated. To establish the AVP-eGFP Tg rat as a unique model for an analysis of
      AVP dynamics in vivo, we first examined the in vivo molecular dynamics of the AVP
      eGFP fusion gene, and then the release of GFP in response to physiological
      stimuli. Double immunoelectron microscopy demonstrated that GFP was specifically
      localized in neurosecretory vesicles of AVP neurons in this Tg rat. After
      stimulation of the posterior pituitary with high potassium we demonstrated the
      exocytosis of AVP neurosecretory vesicles containing GFP at the ultrastructural
      level. Biochemical analyses indicated that the AVP-eGFP fusion gene is subjected
      to in vivo post-translational modifications like the native AVP gene, and is
      packaged into neurosecretory vesicles as a fusion protein: copeptin1-14 -GFP.
      Moreover, GFP release into the circulating blood appeared to be augmented after
      osmotic stimulation, like native AVP. Thus, here we show for the first time the
      in vivo molecular processing of the AVP-eGFP fusion gene and stimulated secretion
      after osmotic stimulation in rats. Because GFP behaved like native AVP in the
      hypothalamo-pituitary axis, and in particular was released into the circulation
      in response to a physiological stimulus, the AVP-eGFP Tg rat model appears to be
      a powerful tool for analyzing neuroendocrine systems at the organismal level.

PMID- 25846301
TI  - Ritonavir-boosted protease inhibitor based therapy: a new strategy in chronic
      hepatitis C therapy.
AB  - Chronic hepatitis C virus (HCV) infection is a worldwide health issue. All oral
      therapies are quickly replacing peg-interferon-based treatment regimens.
      Developing effective, well tolerated, treatments accessible for difficult to
      treat populations remains an unmet need. Ritonavir, an HIV-1 protease inhibitor,
      has pharmacokinetic properties that enhance the activity of concomitantly
      administered direct acting antivirals against HCV. Ritonavir inhibits Cytochrome
      P450 isozyme 3A4, diminishing first pass effect and hepatic metabolism, changing
      the pharmacokinetic parameters of Cytochrome P450 isozyme 3A4 substrates. When
      combined with the HCV protease inhibitor paritaprevir, ritonavir increases mean
      area under the curve, allowing once daily dosing. While Phase II and III clinical
      trials with ritonavir-boosted paritaprevir, ombitasvir, and dasabuvir
      demonstrated high efficacy in those with HCV infection, drug-drug interactions
      warrant cautious use of ritonavir in specific patient populations. Consideration
      of the patients' full medication list is imperative due to the ubiquitous nature
      of the Cytochrome P450 isozyme 3A4 system. 

PMID- 25846299
TI  - The aqueous phase of Alzheimer's disease brain contains assemblies built from ~4
      and ~7 kDa Abeta species.
AB  - INTRODUCTION: Much knowledge about amyloid beta (Abeta) aggregation and toxicity
      has been acquired using synthetic peptides and mouse models, whereas less is
      known about soluble Abeta in human brain. METHODS: We analyzed aqueous extracts
      from multiple AD brains using an array of techniques. RESULTS: Brains can contain
      at least four different Abeta assembly forms including: (i) monomers, (ii) a ~7
      kDa Abeta species, and larger species (iii) from ~30-150 kDa, and (iv) >160 kDa.
      High molecular weight species are by far the most prevalent and appear to be
      built from ~7 kDa Abeta species. The ~7 kDa Abeta species resist denaturation by
      chaotropic agents and have a higher Abeta42/Abeta40 ratio than monomers, and are
      unreactive with antibodies to Asp1 of Ab or APP residues N-terminal of Asp1.
      DISCUSSION: Further analysis of brain-derived ~7 kDa Abeta species, the mechanism
      by which they assemble and the structures they form should reveal therapeutic and
      diagnostic opportunities.

PMID- 25846302
TI  - Transperineal ultrasonography for labor management: accuracy and reliability.
AB  - OBJECTIVE: To compare ultrasound measurements and clinical assessments of
      cervical dilatation, fetal head station and fetal head position. DESIGN:
      Prospective, observational study. SETTING: Tertiary care center (Ankara
      University Hospital), labor ward. POPULATION: Forty-three women in labor.
      METHODS: Women were prospectively evaluated through simultaneous examinations (79
      in total). Dilatation, head station, and position were recorded via digital
      examination whenever possible and were compared with ultrasonographic
      measurements of dilatation, angle of progression, head-perineum distance, and
      head position by two independent operators. Operators were blinded to each
      other's findings. MAIN OUTCOME MEASURES: Agreement between sonographic
      measurements and digital examinations. RESULTS: Ultrasonographic assessment of
      dilatation correlated significantly with digital examination. The interclass
      correlation coefficient of the two methods was 0.82 (95% confidence interval 0.73
      0.88). Ultrasonography showed a mean lower cervical dilatation of 10 mm (95%
      limits of agreement: -36 to 16 mm) compared with digital examination. The angle
      of progression and head-perineum distances correlated moderately with the
      palpated head station (Pearson's correlation coefficients: 0.55 and -0.42,
      respectively; p < 0.001). Position could only be assessed in 40 of 79
      examinations by digital examinations and the results showed low agreement with
      ultrasound findings. CONCLUSION: We observed good agreement between clinical and
      ultrasound assessment of dilatation, moderate agreement in assessing fetal
      station and low agreement assessing head position.

PMID- 25846303
TI  - An aberration-corrected STEM study of structural defects in epitaxial GaN thin
      films grown by ion beam assisted MBE.
AB  - Ion-beam assisted molecular-beam epitaxy was used for direct growth of epitaxial
      GaN thin films on super-polished 6H-SiC(0001) substrates. The GaN films with
      different film thicknesses were studied using reflection high energy electron
      diffraction, X-ray diffraction, cathodoluminescence and primarily aberration
      corrected scanning transmission electron microscopy techniques. Special attention
      was devoted to the microstructural characterization of GaN thin films and the GaN
      SiC interface on the atomic scale. The results show a variety of defect types in
      the GaN thin films and at the GaN-SiC interface. A high crystalline quality of
      the produced hexagonal GaN thin films was demonstrated. The gained results are
      discussed. 

PMID- 25846304
TI  - Electronic structure of MgS and MgYb2S4: Electron Energy-Loss Spectroscopy and
      self-consistent multiple scattering calculations.
AB  - The electronic structure of MgS and MgYb2S4 have been studied using the fine
      structure of the Mg-K, S-K, Mg-L2,3, S-L2,3 and Yb-N5 edges measured by electron
      energy-loss spectroscopy (EELS). Our experimental results are compared with real
      space full multiple scattering calculations as incorporated in the FEFF9.6 code.
      All edges are very well reproduced. Total and partial densities of states have
      been calculated. The calculated densities of states of Mg and S are similar in
      both compounds. The energy distribution of these states suggests a covalent
      nature for both materials. For MgYb2S4 a band gap smaller than for MgS is
      predicted. In this compound the top of the valence band and the bottom of the
      conduction band are dominated by Yb states. 

PMID- 25846305
TI  - Physical activity and academic achievement in a Swedish elementary school.

PMID- 25846306
TI  - Kall, Linden, and Nilsson respond: the impact of a physical activity intervention
      program on academic achievement.

PMID- 25846307
TI  - Out-of-school time activity participation among US--immigrant youth.
AB  - BACKGROUND: Structured out-of-school time (OST) activities are associated with
      positive academic and psychosocial outcomes. METHODS: Data came from the 2007
      National Survey of Children's Health, restricted to 36,132 youth aged 12-17
      years. Logistic regression models were used to examine the joint effects of
      race/ethnicity and immigrant family type on the participation in OST activities.
      RESULTS: Compared with US-born (USB) non-Hispanic White youth with USB parents,
      USB Hispanic youth with USB parents were less likely to participate in sports,
      whereas non-Hispanic Black youth with immigrant parents were more likely to
      participate in sports. White youth with at least 1 immigrant parent had higher
      odds of participating in after-school clubs. All Hispanic youth were less likely
      to participate in after-school clubs. USB Hispanic youth, USB Black youth, and
      White youth and "other" youth with at least 1 immigrant parent had higher odds of
      engaging in community services. Youth from immigrant families had lower odds of
      doing paid work. CONCLUSIONS: Hispanic youth were less likely to participate in
      OST activities. Non-Hispanic youth with immigrant parents did not engage in fewer
      OST activities compared with USB White youth with USB parents. Intervention and
      recruitment strategies for OST activities may need to be customized for immigrant
      groups.

PMID- 25846309
TI  - Longitudinal changes in beliefs by stage of physical activity adoption in Iranian
      girls.
AB  - BACKGROUND: The aims of this study were to examine the relationships among
      physical activity (PA)-related beliefs and to determine to what extent Iranian
      adolescents in different stages of PA adoption differ in perceived benefits and
      barriers during a 3-year transition from junior high school to high school.
      METHODS: Data were collected from female adolescents in 2010 (N = 558), of whom
      412 provided follow-up data in 2013. One-way analysis of variance and logistic
      regression were conducted for statistical analysis. RESULTS: Participants in the
      action and maintenance stages reported the greatest agreement with benefits. Pre
      contemplators were about 4 times more likely to cite "not enough time" than
      preparers (OR = 3.95). Pre-contemplators were over 4 times more likely to cite
      not liking exercise than those in action and maintenance stages at baseline (OR =
      4.32 and 4.85), a finding which was maintained at follow-up (OR = 3.66 and 8.65).
      CONCLUSIONS: These findings could help with the creation of interventions
      tailored to encourage pre-contemplators to progress toward adoption of PA.
      Providing transportation supports, enhancing time management, and mitigating
      boredom may be helpful strategies either to prevent relapse in adoption stages or
      to move females in early stages of change toward action and maintenance.

PMID- 25846308
TI  - Investigating stakeholder attitudes and opinions on school-based human
      papillomavirus vaccination programs.
AB  - BACKGROUND: In several countries worldwide, school-based human papillomavirus
      (HPV) vaccination programs have been successful; however, little research has
      explored US stakeholders' acceptance toward school-based HPV vaccination
      programs. METHODS: A total of 13 focus groups and 12 key informant interviews (N
      = 117; 85% females; 66% racial/ethnic minority) were conducted with 5 groups of
      stakeholders: parents of adolescent girls, parents of adolescent boys, adolescent
      girls, middle school nurses, and middle school administrators throughout the 5
      public health regions of New Mexico. RESULTS: All groups of stakeholders lacked
      knowledge on HPV and HPV vaccines. Stakeholders were interested in--but
      apprehensive about--the benefits of HPV vaccination. Despite previous literature
      showing the benefits of using middle schools as an HPV vaccination site,
      stakeholders did not deem middle schools as a viable site for vaccination. Nurses
      reported that using the school as an HPV vaccination site had not occurred to
      them; parents and adolescents stated they were uncertain about using this type of
      program. School administrators indicated that they lacked implementation
      authority. CONCLUSIONS: Our study uncovered barriers to using middle schools as a
      site of HPV vaccination. Resources should be directed toward increased support
      and education for middle school nurses who function as opinion leaders relevant
      to the uptake of HPV vaccination.

PMID- 25846310
TI  - From the school health education study to the national health education
      standards: concepts endure.
AB  - BACKGROUND: The landmark School Health Education Study (SHES) project influenced
      by the conceptual approach to teaching and learning provides perspective on
      modern school health instruction. Conceptual education, the cornerstone of the
      SHES curriculum framework (CF), Health Education: A Conceptual Approach to
      Curriculum Design, fosters a student's understanding of information that develops
      with experience. METHODS: Data were collected through content analysis of the
      SHES CF and the National Health Education Standards: Achieving Excellence (NHES),
      2nd edition. Similarity of essential framework elements was established. Inter
      rater reliability was established. RESULTS: Alignment of the SHES components with
      the NHES reveals parallel conceptual structures around which to develop
      curriculum. CONCLUSIONS: The conceptual approach to curriculum planning has
      enduring value. It provides a foundation for teaching and learning that is
      adaptable, flexible, and can maintain permanence in conjunction with emerging
      scientific evidence and cultural and political influences on health behavior.

PMID- 25846311
TI  - High school students' experiences of bullying and victimization and the
      association with school health center use.
AB  - BACKGROUND: Bullying and victimization are ongoing concerns in schools. School
      health centers (SHCs) are well situated to support affected students because they
      provide crisis intervention, mental health care, and broader interventions to
      improve school climate. This study examined the association between urban
      adolescents' experiences of school-based bullying and victimization and their use
      of SHCs. METHODS: Data was analyzed from 2063 high school students in 5 Northern
      California school districts using the 2009-2010 California Healthy Kids Survey.
      Chi-square tests and multivariate logistic regression were used to measure
      associations. RESULTS: Students who were bullied or victimized at school had
      significantly higher odds of using the SHCs compared with students who were not,
      and were also significantly more likely to report confidentiality concerns. The
      magnitude of associations was largest for Asian/Pacific Islander students, though
      this was likely due to greater statistical power. African American students
      reported victimization experiences at approximately the same rate as their peers,
      but were significantly less likely to indicate they experienced bullying.
      CONCLUSIONS: Findings suggest that SHCs may be an important place to address
      bullying and victimization at school, but confidentiality concerns are barriers
      that may be more common among bullied and victimized youth.

PMID- 25846312
TI  - Comparison of height, weight, and body mass index data from state-mandated school
      physical fitness testing and a districtwide surveillance project.
AB  - BACKGROUND: Approximately one third of California school-age children are
      overweight or obese. Legislative approaches to assessing obesity have focused on
      school-based data collection. During 2010-2011, the Chula Vista Elementary School
      District conducted districtwide surveillance and state-mandated physical fitness
      testing (PFT) among fifth grade students. We compared height, weight, and body
      mass index (BMI) to examine measurement differences between the projects.
      METHODS: We assessed demographic characteristics and BMI category frequencies. We
      used paired t-tests to test continuous variables. kappa statistics were used to
      assess categorical agreement. RESULTS: Of 3549 children assessed, 69% were
      Hispanic. Fifty-one percent were boys. Mean heights, weights, and BMIs were
      significantly different for each project (p < .0001). Surveillance height (106.7
      165.1 cm) and weight (21.6-90.8 kg) ranges were lesser than PFT ranges (109.2
      180.3 cm and 22.7-98.4 kg). The overall BMI category agreement was good (weighted
      kappa = 0.77). Categorical percentage agreement was highest among normal weight
      children (94.9%) and lowest among underweight children (56.6%). CONCLUSIONS:
      Methodological differences might have resulted in the observed height, weight,
      and BMI differences. As school-based interventions become common, districts
      should carefully consider measurement reliability, training, and data-handling
      protocols to have confidence in their findings.

PMID- 25846313
TI  - Coping and survival skills: the role school personnel play regarding support for
      bullied sexual minority-oriented youth.
AB  - BACKGROUND: Research has shown that bullying has serious health consequences, and
      sexual minority-oriented youth are disproportionately affected. Sexual minority
      oriented youth include lesbian, gay, bisexual, transgender, queer, or questioning
      (LGBTQ) individuals. This study examined the bullying experiences of sexual
      minority-oriented youth in a predominantly rural area of a Midwestern state. The
      purpose of this study was to have bullied youth describe their experiences and to
      present their perspectives. METHODS: Using critical qualitative inquiry, 16 in
      depth interviews were conducted in-person or online with youth, ages 15-20, who
      self-identified as having been bullied based on their perceived minority sexual
      orientation status. RESULTS: The role of supportive school personnel was found to
      be meaningful, and supportive school personnel were mentioned as assisting with
      the coping and survival among this group of bullied sexual minority youth.
      CONCLUSIONS: Supportive school personnel are crucial to the coping and survival
      of these youth. All school personnel need to be aware of the anti-bullying
      policies in their school corporations. They may then work to strengthen and
      enforce their policies for the protection of bullied youth.

PMID- 25846314
TI  - Creating a school-based eye care program.

PMID- 25846315
TI  - Posterior Shoulder Instability in Throwing Athletes: A Case-Matched Comparison of
      Throwers and Non-Throwers.
AB  - PURPOSE: To evaluate the results of arthroscopic capsulolabral repair for the
      treatment of posterior shoulder instability in a throwing athlete cohort when
      compared with non-throwers. METHODS: Forty-eight overhead-throwing athletes
      undergoing arthroscopic posterior capsulolabral reconstruction were case matched
      with 48 non-throwing athletes. These cohorts were followed as they underwent
      posterior capsulolabral reconstruction by measuring shoulder pain, function,
      return to sport, and operative failures. Operative details such as intra
      articular pathology and repair construct were also recorded. RESULTS: At a mean
      follow-up of 37 months (range, 12 to 97 months) postoperatively, no statistical
      differences were noted between throwers and non-throwers regarding American
      Shoulder and Elbow Surgeons scores, stability, strength, or range of motion.
      Sixty percent of throwing athletes were able to return to their preinjury level
      of competitive throwing. Throwers with a discrete labral tear intraoperatively
      had a 10-fold increased likelihood of returning to sport (odds ratio, 9.6; P =
      .012). Similarly, throwers who had suture anchor constructs showed a 10-fold
      increased likelihood of returning to play compared with anchor-less repairs (odds
      ratio, 9.6; P = .012). Non-throwers showed no variability by labral findings or
      fixation techniques. Pitchers had equivocal outcome scores when compared with
      other throwers but had poorer return-to-play rates (50% v 60% full return).
      CONCLUSIONS: Arthroscopic capsulolabral plication for unidirectional posterior
      shoulder instability is an effective treatment for overhead-throwing athletes.
      Intraoperatively, achieving an adequate capsular plication and stabilizing the
      repair with suture anchors will give this athletic population the best odds of
      returning to competitive sports. LEVEL OF EVIDENCE: Level III, retrospective
      comparative study.

PMID- 25846316
TI  - Honokiol suppresses metastasis of renal cell carcinoma by targeting KISS1/KISS1R
      signaling.
AB  - Renal cell carcinoma (RCC) is a common urological cancer worldwide and is known
      to have a high risk of metastasis, which is considered responsible for more than
      90% of cancer associated deaths. Honokiol is a small-molecule biphenol isolated
      from Magnolia spp. bark and has been shown to be a potential anticancer agent
      involved in multiple facets of signal transduction. In this study, we
      demonstrated that honokiol inhibited the invasion and colony formation of highly
      metastatic RCC cell line 786-0 in a dose-dependent manner. DNA-microarray data
      showed the significant upregulation of metastasis-suppressor gene KISS1 and its
      receptor, KISS1R. The upregulation was confirmed by qRT-PCR analysis.
      Overexpression of KISS1 and KISS1R was detected by western blotting at the
      translation level as well. Of note, the decreased invasive and colonized
      capacities were reversed by KISS1 knockdown. Taken together, the results first
      indicate that activation of KISS1/KISS1R signaling by honokiol suppresses
      multistep process of metastasis, including invasion and colony formation, in RCC
      cells 786-0. Honokiol may be considered as a natural agent against RCC
      metastasis. 

PMID- 25846317
TI  - Noonan syndrome-like disorder with loose anagen hair: a second case with
      neuroblastoma.
AB  - Noonan-like syndrome with loose anagen hair (NSLH), also known as Mazzanti
      syndrome, is a RASopathy characterized by craniofacial features resembling Noonan
      syndrome, cardiac defects, cognitive deficits and behavioral issues, reduced
      growth generally associated with GH deficit, darkly pigmented skin, and an unique
      combination of ectodermal anomalies. Virtually all cases of NSLH are caused by an
      invariant and functionally unique mutation in SHOC2 (c.4A>G, p.Ser2Gly). Here, we
      report on a child with molecularly confirmed NSLH who developed a neuroblastoma,
      first suspected at the age 3 months by abdominal ultrasound examination. Based on
      this finding, scanning of the SHOC2 coding sequence encompassing the c.4A>G
      change was performed on selected pediatric cohorts of malignancies documented to
      occur in RASopathies (i.e., neuroblastoma, brain tumors, rhabdomyosarcoma, acute
      lymphoblastic, and myeloid leukemia), but failed to identify a functionally
      relevant cancer-associated variant. While these results do not support a major
      role of somatic SHOC2 mutations in these pediatric cancers, this second instance
      of neuroblastoma in NSLAH suggests a possible predisposition to this malignancy
      in subjects heterozygous for the c.4A>G SHOC2 mutation.

PMID- 25846318
TI  - Verification of chicken Nanog as an epiblast marker and identification of chicken
      PouV as Pou5f3 by newly raised antibodies.
AB  - Pluripotency is an important feature of early embryonic cells of multicellular
      organisms. Recent advances in stem cell research have shown that Nanog and Pou5f1
      (Oct3/4) play important roles in mammalian pluripotency. However, whether these
      molecules exert conserved functions in other species remains unknown. Although
      the epiblast of the early chicken embryo would provide a useful experimental
      model, a lack of antibodies against chicken Nanog (cNanog) and chicken
      PouV/Pou5f3 (cPouV) proteins has hampered intensive investigation. Here we report
      newly raised polyclonal antibodies that specifically recognize cNanog and cPouV
      proteins. The specificity and sensitivity of the antibodies were validated by
      both western blotting and immunostaining with transfected 293T cells and chicken
      embryonic tissues. Immunohistochemistry using these antibodies revealed that
      cNanog protein was specifically localized in epiblastic cells and germ cells. In
      contrast, cPouV expression was seen almost ubiquitously. We also found that
      chicken epiblast-derived colony-forming cells that morphologically resemble mouse
      embryonic stem cells were cNanog-positive, implying that these colony-forming
      cells possess pluripotency. The anti-cPouV antibody further enabled us to
      identify a previously unknown region at the N-terminus of the cPouV protein
      containing a characteristic motif that is absent in mammalian Pou5f1. Thus, the
      antibodies raised in this study are useful tools for studying the functions of
      cNanog and cPouV at the protein level and the molecular mechanisms of chicken
      pluripotency. 

PMID- 25846319
TI  - Gut Microbiota: The Conductor in the Orchestra of Immune-Neuroendocrine
      Communication.
AB  - PURPOSE: It is well established that mammals are so-called super-organisms that
      coexist with a complex microbiota. Growing evidence points to the delicacy of
      this host-microbe interplay and how disruptive interventions could have lifelong
      consequences. The goal of this article was to provide insights into the potential
      role of the gut microbiota in coordinating the immune-neuroendocrine cross-talk.
      METHODS: Literature from a range of sources, including PubMed, Google Scholar,
      and MEDLINE, was searched to identify recent reports regarding the impact of the
      gut microbiota on the host immune and neuroendocrine systems in health and
      disease. FINDINGS: The immune system and nervous system are in continuous
      communication to maintain a state of homeostasis. Significant gaps in knowledge
      remain regarding the effect of the gut microbiota in coordinating the immune
      nervous systems dialogue. Recent evidence from experimental animal models found
      that stimulation of subsets of immune cells by the gut microbiota, and the
      subsequent cross-talk between the immune cells and enteric neurons, may have a
      major impact on the host in health and disease. IMPLICATIONS: Data from rodent
      models, as well as from a few human studies, suggest that the gut microbiota may
      have a major role in coordinating the communication between the immune and
      neuroendocrine systems to develop and maintain homeostasis. However, the
      underlying mechanisms remain unclear. The challenge now is to fully decipher the
      molecular mechanisms that link the gut microbiota, the immune system, and the
      neuroendocrine system in a network of communication to eventually translate these
      findings to the human situation, both in health and disease.

PMID- 25846320
TI  - New FDA-Approved Disease-Modifying Therapies for Multiple Sclerosis.
AB  - PURPOSE: Interferon injectables and glatiramer acetate have served as the primary
      disease-modifying treatments for multiple sclerosis (MS) since their introduction
      in the 1990s and are first-line treatments for relapsing-remitting forms of MS
      (RRMS). Many new drug therapies were launched since early 2010, expanding the
      drug treatment options considerably in a disease state that once had a limited
      treatment portfolio. The purpose of this review is to critically evaluate the
      safety profile and efficacy data of disease-modifying agents for MS approved by
      the US Food and Drug Administration (FDA) from 2010 to the present and provide
      cost and available pharmacoeconomic data about each new treatment. METHODS: Peer
      reviewed clinical trials, pharmacoeconomic studies, and relevant
      pharmacokinetic/pharmacologic studies were identified from MEDLINE (January 2000
      December 2014) by using the search terms multiple sclerosis, fingolimod,
      teriflunomide, alemtuzumab, dimethyl fumarate, pegylated interferon,
      peginterferon beta-1a, glatiramer 3 times weekly, and pharmacoeconomics.
      Citations from available articles were also reviewed for additional references.
      The databases publically available at www.clinicaltrials.gov and www.fda.gov were
      searched for unpublished studies or studies currently in progress. FINDINGS: A
      total of 5 new agents and 1 new dosage formulation were approved by the FDA for
      the treatment of RRMS since 2010. Peginterferon beta-1a and high-dose glatiramer
      acetate represent 2 new effective injectable options for MS that reduce burden of
      administration seen with traditional interferon and low-dose glatiramer acetate.
      Fingolimod, teriflunomide, and dimethyl fumarate represent new oral agents
      available for MS, and their efficacy in reducing annualized relapse rates is 48%
      to 55%, 22% to 36.3%, and 44% to 53%, respectively, compared with placebo.
      Alemtuzumab is a biologic given over a 2-year span that reduced annualized
      relapse rates by 55% in treatment-naive patients and by 49% in patients relapsing
      on prior disease-modifying agents. Treatment emergent adverse effects were common
      with all new drug treatments. The cost of treating MS remains high, because MS
      therapies accounted for the highest spending growth of any specialty drug class
      in 2013. Most therapies cost, on average, US $6000/mo based on wholesale
      acquisition cost, and few cost-benefit studies are available for new treatments.
      IMPLICATIONS: With expansion of new treatments, patients and providers now have
      multiple options and improved flexibility in managing MS. The relative place in
      therapy of new treatments is unknown, and treatment decisions are largely based
      on patient preference, efficacy, and risk potential. The cost of treating MS
      continues to be high, even with more treatment options available.

PMID- 25846321
TI  - The Role of Microbiota on the Gut Immunology.
AB  - PURPOSE: The human gut contains >100 trillion microbes. This microbiota plays a
      crucial role in the gut homeostasis. Importantly, the microbiota contributes to
      the development and regulation of the gut immune system. Dysbiosis of the gut
      microbiota could also cause several intestinal and extraintestinal diseases. Many
      experimental studies help us to understand the complex interplay between the host
      and microbiota. METHODS: This review presents our current understanding of the
      mucosal immune system and the role of gut microbiota for the development and
      functionality of the mucosal immunity, with a particular focus on gut-associated
      lymphoid tissues, mucosal barrier, TH17 cells, regulatory T cells, innate
      lymphoid cells, dendritic cells, and IgA-producing B cells and plasma cells.
      FINDINGS: Comparative studies using germ-free and conventionally-raised animals
      reveal that the presence of microbiota is important for the development and
      regulation of innate and adaptive immune systems. The host-microbial symbiosis
      seems necessary for gut homeostasis. However, the precise mechanisms by which
      microbiota contributes to development and functionality of the immune system
      remain to be elucidated. IMPLICATIONS: Understanding the complex interplay
      between the host and microbiota and further investigation of the host-microbiota
      relationship could provide us the insight into the therapeutic and/or preventive
      strategy for the disorders related to dysbiosis of the gut microbiota.

PMID- 25846322
TI  - In vitro bone strain distributions in a sample of primate pelves.
AB  - The pelvis is a critical link in the hindlimb locomotor system and has a central
      role in resisting loads associated with locomotion, but our understanding of its
      structural biomechanics is quite limited. Empirical data on how the pelvis
      responds to the loads it encounters are important for understanding pelvic
      adaptation to locomotion, and for testing hypotheses regarding how the pelvis is
      adapted to its mechanical demands. This paper presents in vitro strain gauge data
      on a sample of monkey and ape cadaveric specimens (Macaca, Papio, Ateles,
      Hylobates), and assesses strain magnitudes and distributions through the bones of
      the pelvis: the ilium, ischium and pubis. Pelves were individually mounted in a
      materials testing system, loads were applied across three hindlimb angular
      positions, and strains were recorded from 18 locations on the pelvic girdle. Peak
      principal strains range from 2000 to 3000 MUepsilon, similar to peak strains
      recorded from other mammals in vivo. Although previous work has suggested that
      the bones of the pelvis may act as bent beams, this study suggests that there are
      likely additional loading regimes superimposed on bending. Specifically, these
      data suggest that the ilium is loaded in axial compression and torsion, the
      ischium in torsion, the pubic rami in mediolateral bending, and the pubic
      symphysis is loaded in a combination of compression and torsion. Compressive
      strains dominate the pelves of all species representatives. Shear strains change
      with limb position; hip flexion at 45 degrees  induces smaller shear strains than
      mid-stance (90 degrees ) or hip extension (105 degrees ). The pelvic girdle is a
      complex structure that does not lend itself easily to modeling, but finite
      element analyses may prove useful to generate and refine hypotheses of pelvic
      biomechanics.

PMID- 25846323
TI  - Kinematics and knee muscle activation during sit-to-stand movement in women with
      knee osteoarthritis.
AB  - BACKROUND: The purpose of this study was to compare joint kinematics, knee and
      trunk muscle activation and co-activation patterns during a sit-to-stand movement
      in women with knee osteoarthritis and age-matched controls. METHODS: Eleven women
      with knee osteoarthritis (mean and standard deviation, age: 66.90, 4.51 years,
      height: 1.63, 0.02 m, mass: 77.63, 5.4 kg) and eleven healthy women (mean and
      standard deviation, age: 61.90, 3.12 years, height: 1.63 m, 0.03, mass: 78.30,
      4.91 kg) performed a Sit to Stand movement at a self-selected slow, normal and
      fast speed. Three-dimensional joint kinematics of the lower limb, vertical ground
      reaction forces and electromyographic activity of the biceps femoris vastus
      lateralis and erectus spinae were recorded bilaterally. FINDINGS: A two-way ANOVA
      showed that the osteoarhtitis group performed the sit to stand task using a
      smaller knee and hip range of motion compared with the control group while no
      differences in temporal kinematics and ground reaction force-related parameters
      were observed. In addition, women with osteoarhtritis displayed significantly
      lower vastus lateralis coupled with a higher biceps feomoris electromyographic
      activity and higher agonist-antagonist co-contraction and co-activation than
      asymptomatic women. The activation of erectus spinae was not different between
      groups. INTERPRETATION: Results indicate that patients with moderate knee
      osteoarthritis rise from the chair using greater knee muscle co-contraction,
      earlier and greater activation of the hamstrings which results in reduced hip and
      knee range of motion. This may be a way to overcome the pain and potential muscle
      atrophy of knee extensor muscles without compromising overall task duration.

PMID- 25846324
TI  - Angular stable lateral plating is a valid alternative to conventional plate
      fixation in the proximal phalanx. A biomechanical study.
AB  - BACKGROUND: Dorsal plating is commonly used in proximal phalanx fractures but it
      bears the risk of interfering with the extensor apparatus. In this study, dorsal
      and lateral plating fixation methods are compared to assess biomechanical
      differences using conventional 1.5mm non-locking plates and novel 1.3mm lateral
      locking plates. METHODS: Twenty-four fresh frozen human cadaveric proximal
      phalanges were equally divided into four groups. An osteotomy was set at the
      proximal metaphyseal-diaphyseal junction and fixed with either dorsal (group A)
      or lateral (group B) plating using a 1.5mm non-locking plate, or lateral plating
      with a novel 1.3mm locking plate with bicortical (group C) or unicortical (group
      D) screws. The specimens were loaded in axial, dorsovolar and mediolateral
      direction to assess fixation stiffness followed by a cyclic destructive test in
      dorsovolar loading direction. FINDINGS: Axial stiffness was highest in group D
      (mean 321.02, SEM 21.47N/mm) with a significant difference between groups D and B
      (P=0.033). Locking plates (groups C and D) were stiffer than non-locking plates
      under mediolateral loading (P=0.007), no significant differences were noted under
      dorsovolar loading. Furthermore, no significant differences were observed under
      cyclic loading to failure between any of the study groups. INTERPRETATION: No
      considerable biomechanical advantage of using a conventional 1.5mm dorsal non
      locking plate was identified over the novel 1.3mm lateral locking plate in the
      treatment of proximal phalanx fractures. Since the novel low-profile plate is
      less disruptive to the extensor mechanism, it should be considered as a valid
      alternative.

PMID- 25846325
TI  - Electromyographic activity of erector spinae and external oblique muscles during
      trunk lateral bending and axial rotation in patients with adolescent idiopathic
      scoliosis and healthy subjects.
AB  - BACKGROUND: The aim of this study was to analyze electrical activity of trunk
      muscles in adolescent idiopathic scoliosis patients and healthy subjects during
      trunk lateral bending and rotation movements. METHODS: Ten patients with right
      thoracic scoliosis [Cobb angle: 29.1 degrees  (10.4 degrees )] and 10 control
      adolescents were studied. Electrical activities of erector spinae muscle at 6th
      and 10th thoracic and 3rd lumbar vertebral level, and external oblique muscles
      were measured bilaterally during the right and left bending from standing and
      prone positions, and trunk rotation in sitting position. FINDINGS: In trunk
      rotation to the right, the right-side external oblique (antagonist) muscle in
      scoliosis group was greater than that in control group (p<0.05). In left bending
      from standing position, in scoliosis group, the antagonistic activity of EST6
      muscle was greater than its agonistic activity (p<0.05). Also, in the right
      bending motion, the agonistic activity of external oblique of scoliosis group was
      higher than that of control group (p=0.02). During the left bending from prone
      position, right-side EST6 and right-side ESL3 muscles of scoliosis group were
      greater than that of control group (p<0.05). INTERPRETATION: In left bending from
      standing position, in scoliosis group, the greater antagonistic activity of
      erector spinae muscle at 6th thoracic vertebral level than its agonistic
      activity, indicates that scoliosis is associated with asymmetrical muscle
      activity. Lateral bending from standing position is appropriate test to
      distinguish between scoliosis and control subjects. In scoliosis, the
      asymmetrical muscle activity is not an inherent characteristic since it was not
      displayed in all back motions.

PMID- 25846326
TI  - Red meat subtypes and colorectal cancer risk.

PMID- 25846327
TI  - Subclinical hypothyroidism: a historical view and shifting prevalence.
AB  - BACKGROUND AND AIMS: Accurate diagnosis and treatment of subclinical
      hypothyroidism (SCH) is challenging in clinical practice because of differing
      upper limits of normal (ULN) for thyroid-stimulating hormone (TSH). This review
      summarises the various definitions of SCH and their impact on reported SCH
      prevalence. METHODOLOGY: Articles reporting the prevalence of SCH in relation to
      the ULN of TSH in human studies were identified through an English-language
      PubMed search for 'subclinical hypothyroidism,' 'prevalence,' and 'TSH' within
      the title and/or abstract. Relevant articles and related literature were selected
      for inclusion. RESULTS: Estimates for the prevalence of SCH varied by sex, age,
      race/ethnicity, and geographic location (range, 0.4-16.9%). Higher rates of SCH
      were consistently reported in women (0.9-16.9%) and older individuals (2.7
      16.9%). However, the ULN of TSH in those considered free of thyroid disease and
      not at risk increased progressively with age, suggesting that reports of SCH
      prevalence in elderly people may be overestimated. Multiple studies reported an
      increased risk of progression to overt hypothyroidism among individuals with
      elevated TSH and antithyroid antibodies. CONCLUSIONS: Given the variable
      definition of SCH based on an inconsistent ULN for TSH, it is currently difficult
      to ascertain the true prevalence of SCH and to correctly label and treat patients
      with SCH; use of age-adjusted definitions may be considered when assessing
      prevalence. A diagnosis of SCH does not necessarily merit treatment, especially
      if TSH elevations are transient (i.e. not persistent for > 3-6 months) and the
      patient lacks other risk factors for developing overt hypothyroidism.

PMID- 25846328
TI  - In situ adaptive response to climate and habitat quality variation: spatial and
      temporal variation in European badger (Meles meles) body weight.
AB  - Variation in climatic and habitat conditions can affect populations through a
      variety of mechanisms, and these relationships can act at different temporal and
      spatial scales. Using post-mortem badger body weight records from 15 878
      individuals captured across the Republic of Ireland (7224 setts across ca. 15 000
      km(2) ; 2009-2012), we employed a hierarchical multilevel mixed model to evaluate
      the effects of climate (rainfall and temperature) and habitat quality (landscape
      suitability), while controlling for local abundance (unique badgers
      caught/sett/year). Body weight was affected strongly by temperature across a
      number of temporal scales (preceding month or season), with badgers being heavier
      if preceding temperatures (particularly during winter/spring) were warmer than
      the long-term seasonal mean. There was less support for rainfall across different
      temporal scales, although badgers did exhibit heavier weights when greater
      rainfall occurred one or 2 months prior to capture. Badgers were also heavier in
      areas with higher landscape habitat quality, modulated by the number of
      individuals captured per sett, consistent with density-dependent effects reducing
      weights. Overall, the mean badger body weight of culled individuals rose during
      the study period (2009-2012), more so for males than for females. With predicted
      increases in temperature, and rainfall, augmented by ongoing agricultural land
      conversion in this region, we project heavier individual badger body weights in
      the future. Increased body weight has been associated with higher fecundity,
      recruitment and survival rates in badgers, due to improved food availability and
      energetic budgets. We thus predict that climate change could increase the badger
      population across the Republic of Ireland. Nevertheless, we emphasize that,
      locally, populations could still be vulnerable to extreme weather variability
      coupled with detrimental agricultural practice, including population management.

PMID- 25846329
TI  - No evidence for reduction of opioid-withdrawal symptoms by cannabis smoking
      during a methadone dose taper.
AB  - BACKGROUND AND OBJECTIVES: To support medication development with cannabinoids,
      smoked cannabis has been said to alleviate symptoms of opioid withdrawal. We
      evaluated that hypothesis. METHODS: We analyzed data from the methadone-taper
      phase of a clinical trial we had conducted. Participants were 116 outpatient
      heroin and cocaine users (of whom 46 were also cannabis users) who stayed for the
      10-week taper. Main outcome measures were weekly urine screens for cannabinoids,
      plus every-two-week assessments of opioid-withdrawal symptoms. RESULTS: Opioid
      withdrawal scores did not differ overall between users and nonusers of cannabis.
      In a lagged analysis in the 46 users, there was a slight (not statistically
      significant) indication that weeks of higher opiate-withdrawal symptoms preceded
      weeks of cannabis use (effect-size r = .20, 95% CI -.10 to .46, p = .52). Even if
      this finding is taken to suggest self-medication with cannabis, a lagged analysis
      in the other temporal direction showed no indication that cannabis use predicted
      lower opiate-withdrawal symptoms the next week (effect-size r = .01, 95% CI -.28
      to .30, p = .69). These findings persisted in sensitivity analyses controlling
      for each of 17 potential confounds. DISCUSSION AND CONCLUSION: With our findings,
      the clinical evidence for smoked cannabis as a reducer of opioid-withdrawal
      symptoms moves slightly further from "inconclusive" or "mixed" and closer to
      negative, at least in the context of a methadone dose taper like the one used
      here. SCIENTIFIC SIGNIFICANCE: This finding may remove one rationale for
      medication development using cannabinoids to treat opioid withdrawal, but leaves
      other rationales intact.

PMID- 25846330
TI  - Benchmarking of commercially available CHO cell culture media for antibody
      production.
AB  - In this study, eight commercially available, chemically defined Chinese hamster
      ovary (CHO) cell culture media from different vendors were evaluated in batch
      culture using an IgG-producing CHO DG44 cell line as a model. Medium adaptation
      revealed that the occurrence of even small aggregates might be a good indicator
      of cell growth performance in subsequent high cell density cultures. Batch
      experiments confirmed that the culture medium has a significant impact on
      bioprocess performance, but high amino acid concentrations alone were not
      sufficient to ensure superior cell growth and high antibody production. However,
      some key amino acids that were limiting in most media could be identified.
      Unbalanced glucose and amino acids led to high cell-specific lactate and ammonium
      production rates. In some media, persistently high glucose concentrations
      probably induced the suppression of respiration and oxidative phosphorylation,
      known as Crabtree effect, which resulted in high cell-specific glycolysis rates
      along with a continuous and high lactate production. In additional experiments,
      two of the eight basal media were supplemented with feeds from two different
      manufacturers in six combinations, in order to understand the combined impact of
      media and feeds on cell metabolism in a CHO fed-batch process. Cell growth,
      nutrient consumption and metabolite production rates, antibody production, and
      IgG quality were evaluated in detail. Concentrated feed supplements boosted cell
      concentrations almost threefold and antibody titers up to sevenfold. Depending on
      the fed-batch strategy, fourfold higher peak cell concentrations and eightfold
      increased IgG titers (up to 5.8 g/L) were achieved. The glycolytic flux was
      remarkably similar among the fed-batches; however, substantially different
      specific lactate production rates were observed in the different media and feed
      combinations. Further analysis revealed that in addition to the feed additives,
      the basal medium can make a considerable contribution to the ammonium metabolism
      of the cells. The glycosylation of the recombinant antibody was influenced by the
      selection of basal medium and feeds. Differences of up to 50 % in the monogalacto
      fucosylated (G1F) and high mannose fraction of the IgG were observed. 

PMID- 25846331
TI  - Concatemerization increases the inhibitory activity of short, cell-penetrating,
      cationic and tryptophan-rich antifungal peptides.
AB  - There are short cationic and tryptophan-rich antifungal peptides such as the
      hexapeptide PAF26 (RKKWFW) that have selective toxicity and cell penetration
      properties against fungal cells. This study demonstrates that concatemeric
      peptides with tandem repeats of the heptapeptide PAF54 (which is an elongated
      PAF26 sequence) show increased fungistatic and bacteriostatic activities while
      maintaining the absence of hemolytic activity of the monomer. The increase in
      antimicrobial activity of the double-repeated PAF sequences (diPAFs), compared to
      the nonrepeated PAF, was higher (4-8-fold) than that seen for the triple-repeated
      sequences (triPAFs) versus the diPAFs (2-fold). However, concatemerization
      diminished the fungicidal activity against quiescent spores of the filamentous
      fungus Penicillium digitatum. Peptide solubility and sensitivity to proteolytic
      degradation were affected by the design of the concatemers: incorporation of the
      AGPA sequence hinge to separate PAF54 repeats increased solubility while the C
      terminal addition of the KDEL sequence decreased in vitro stability. These
      results led to the design of the triPAF sequence PAF102 of 30 amino acid
      residues, with increased antimicrobial activity and minimal inhibitory
      concentration (MIC) value of 1-5 MUM depending on the fungus. Further
      characterization of the mode-of-action of PAF102 demonstrated that it colocalizes
      first with the fungal cell wall, it is thereafter internalized in an energy
      dependent manner into hyphal cells of the filamentous fungus Fusarium
      proliferatum, and finally kills hyphal cells intracellularly. Therefore, PAF102
      showed mechanistic properties against fungi similar to the parental PAF26. These
      observations are of high interest in the future development of PAF-based
      antimicrobial molecules optimized for their production in biofactories.

PMID- 25846332
TI  - Identification of sucrose synthase in nonphotosynthetic bacteria and
      characterization of the recombinant enzymes.
AB  - Sucrose synthase (SuSy) catalyzes the reversible conversion of sucrose and a
      nucleoside diphosphate into fructose and nucleotide (NDP)-glucose. To date, only
      SuSy's from plants and cyanobacteria, both photosynthetic organisms, have been
      characterized. Here, four prokaryotic SuSy enzymes from the nonphotosynthetic
      organisms Nitrosomonas Europaea (SuSyNe), Acidithiobacillus caldus (SuSyAc),
      Denitrovibrio acetiphilus (SusyDa), and Melioribacter roseus (SuSyMr) were
      recombinantly expressed in Escherichia coli and thoroughly characterized. The
      purified enzymes were found to display high-temperature optima (up to 80  degrees
      C), high activities (up to 125 U/mg), and high thermostability (up to 15 min at
      60  degrees C). Furthermore, SuSyAc, SuSyNe, and SuSyDa showed a clear preference
      for ADP as nucleotide, as opposed to plant SuSy's which prefer UDP. A structural
      and mutational analysis was performed to elucidate the difference in NDP
      preference between eukaryotic and prokaryotic SuSy's. Finally, the physiological
      relevance of this enzyme specificity is discussed in the context of metabolic
      pathways and genomic organization.

PMID- 25846333
TI  - Outer membrane proteins related to SusC and SusD are not required for Cytophaga
      hutchinsonii cellulose utilization.
AB  - Cytophaga hutchinsonii, a member of the phylum Bacteroidetes, employs a novel
      collection of cell-associated proteins to digest crystalline cellulose. Other
      Bacteroidetes rely on cell surface proteins related to the starch utilization
      system (Sus) proteins SusC and SusD to bind oligosaccharides and import them
      across the outer membrane for further digestion. These bacteria typically produce
      dozens of SusC-like porins and SusD-like oligosaccharide-binding proteins to
      facilitate utilization of diverse polysaccharides. C. hutchinsonii specializes in
      cellulose digestion and its genome has only two susC-like genes and two susD-like
      genes. Single and multiple gene deletions were constructed to determine if the
      susC-like and susD-like genes have roles in cellulose utilization. A mutant
      lacking all susC-like and all susD-like genes digested cellulose and grew on
      cellulose as well as wild-type cells. Further, recombinantly expressed SusD-like
      proteins CHU_0547 and CHU_0554 failed to bind cellulose or beta-glucan
      hemicellulosic polysaccharides. The results suggest that the Bacteroidetes Sus
      paradigm for polysaccharide utilization may not apply to the cellulolytic
      bacterium C. hutchinsonii. 

PMID- 25846334
TI  - Engineering the heterologous expression of lanthipeptides in Escherichia coli by
      multigene assembly.
AB  - Lantibiotics are an important class of ribosomally synthesised peptide
      antibiotics with a remarkable pharmacological potential. Structural variants of
      lantibiotics generated by peptide engineering in vivo are an important aspect for
      improving the peptide's efficacy, stability and bioavailability as well as
      production titre, which severely impacts the potential exploitation in
      pharmaceutical applications. Therefore, expression systems are needed which allow
      for a robust genetic access for ample mutagenesis experiments. Based on previous
      heterologous expression of the two-component lanthipeptide lichenicidin (Blialpha
      and Blibeta) in Escherichia coli BLic5, we now employ a multigene assembly
      strategy for recombinant lantibiotic peptide production in the Gram-negative
      host. Two E. coli high copy plasmids for separate and increased expression of a
      two-component lantibiotic were cloned and tested for expression. From these E.
      coli HP expression strains, an up to 100 times increased expression was found
      compared with Bacillus licheniformis I89 and E. coli BLic5. Total expression
      yields reach 4 mg L(-1) for Blialpha and 6 mg L(-1) for Blibeta. The expression
      system developed in this study constitutes an important cornerstone for future in
      vivo peptide engineering studies and is of significance for potential
      applications aiming at higher production titres of ribosomally synthesised, post
      translationally modified peptides. 

PMID- 25846335
TI  - Physiologo-biochemical characteristics of citrate-producing yeast Yarrowia
      lipolytica grown on glycerol-containing waste of biodiesel industry.
AB  - In this study, physiologo-biochemical characteristics of citrate-producing yeast
      Yarrowia lipolytica grown on glycerol-containing waste of biodiesel industry were
      studied by an investigation of growth dynamics, the consumption of glycerol, and
      the fatty acid fractions from waste as well as by measuring the activities of
      enzymes involved in the metabolism of waste. It was shown that Y. lipolytica
      realizes concurrent uptake of glycerol and the fatty acid fractions during
      conversion of glycerol-containing waste, although glycerol was utilized at a
      higher rate than fatty acids. Under optimal feeding of glycerol-containing waste
      by portions of 20 g l(-1), the citric acid production and the ratio between
      citric acid and isocitric acid depended on the strain used. It was revealed that
      wild strain Y. lipolytica VKM Y-2373 produced citrate and isocitrate with a ratio
      of 1.7:1, while the mutant strain Y. lipolytica NG40/UV7 synthesized presumably
      citric acid (122.2 g l(-1)) with a citrate-to-isocitrate ratio of 53:1 and the
      yield of 0.95 g g(-1). 

PMID- 25846336
TI  - Comparative study of MnO2 nanoparticle synthesis by marine bacterium
      Saccharophagus degradans and yeast Saccharomyces cerevisiae.
AB  - Microorganisms are one of the most attractive and simple sources for the
      synthesis of different types of metal nanoparticles. The synthesis of manganese
      dioxide nanoparticles (MnO2 NPs) by microorganisms from reducing potassium
      permanganate was investigated for the first time in the present study. The
      microbial supernatants of the bacterium Saccharophagus degradans ATCC 43961 (Sde
      2-40) and of the yeast Saccharomyces cerevisiae showed positive reactions to the
      synthesis of MnO2 NPs by displaying a change of color in the permanganate
      solution from purple to yellow. KMnO4-specific peaks also disappeared and MnO2
      specific peaks emerged at an absorption maximum of 365 nm in UV-visible
      spectrophotometry. The washed Sde 2-40 cells did not show any ability to
      synthesize MnO2 NPs. The medium and medium constituents of Sde 2-40 showed
      similar positive reactions as supernatants, which indicate the role of the Sde 2
      40 medium constituents in the synthesis of MnO2 NPs. This suggests that
      microorganisms without nanoparticle synthesis ability can be misreported for
      their abilities to synthesize nanoparticles. S. cerevisiae washed cells showed an
      ability to synthesize MnO2 NPs. The strategies of keeping yeast cells in tea bags
      and dialysis membranes showed positive tests for the synthesis of MnO2 NPs. A
      Fourier transform-infrared spectroscopy study suggested roles for the proteins,
      alcoholic compounds, and cell walls of S. cerevisiae cells in the synthesis of
      MnO2 NPs. Electron-dispersive X-ray spectroscopy analyses confirmed the presence
      of Mn and O in the sample. X-ray photoelectron spectroscopy revealed
      characteristic binding energies for MnO2 NPs. Transmission electron microscopy
      micrographs revealed the presence of uniformly dispersed hexagonal- and spherical
      shaped particles with an average size of 34.4 nm. The synthesis approach using
      yeast is possible by a simple reaction at low temperature without any need for
      catalysts, templates, or expensive and precise equipment. Therefore, this study
      will be useful for the easy, cost-effective, reliable, and eco-friendly
      production of nanomaterials. 

PMID- 25846337
TI  - Saccharomyces cerevisiae EC-1118 enhances the survivability of probiotic
      Lactobacillus rhamnosus HN001 in an acidic environment.
AB  - The present study attempted to partially characterize and elucidate the viability
      enhancing effect of a yeast strain Saccharomyces cerevisiae EC-1118 on a
      probiotic strain Lactobacillus rhamnosus HN001 under acidic conditions using a
      model system (non-growing cells). The yeast was found to significantly enhance (P
      < 0.05) the viability of the probiotic strain under acidic conditions (pH 2.5 to
      4.0) by 2 to 4 log cycles, and the viability-enhancing effects were observed to
      be influenced by pH, and probiotic and yeast concentrations. Microscopic
      observation and co-aggregation assay revealed that the viability-enhancing effect
      of the yeast could be attributed to direct cell-cell contact co-aggregation
      mediated by yeast cell surface and/or cell wall components or metabolites.
      Furthermore, non-viable yeast cells killed by thermal means were observed to
      enhance the viability of the probiotic strain as well, suggesting that the
      surface and/or cell wall component(s) of the yeast contributing to co-aggregation
      was heat-stable. Cell-free yeast supernatant was also found to enhance the
      viability of the probiotic strain, indicating the presence of protective yeast
      metabolite(s) in the supernatant. These findings laid the foundation for further
      understanding of the mechanism(s) involved and for developing novel microbial
      starter cultures possibly without the use of live yeast for ambient-stable high
      moisture probiotic foods.

PMID- 25846338
TI  - Erratum to: mismatch discrimination in fluorescent in situ hybridization using
      different types of nucleic acids.

PMID- 25846339
TI  - Notch signaling mediates granulocyte-macrophage colony-stimulating factor priming
      induced transendothelial migration of human eosinophils.
AB  - BACKGROUND: Priming with cytokines such as granulocyte-macrophage colony
      stimulating factor (GM-CSF) enhances eosinophil migration and exacerbates the
      excessive accumulation of eosinophils within the bronchial mucosa of asthmatics.
      However, mechanisms that drive GM-CSF priming are incompletely understood. Notch
      signaling is an evolutionarily conserved pathway that regulates cellular
      processes, including migration, by integrating exogenous and cell-intrinsic cues.
      This study investigates the hypothesis that the priming-induced enhanced
      migration of human eosinophils requires the Notch signaling pathway. METHODS:
      Using pan Notch inhibitors and newly developed human antibodies that specifically
      neutralize Notch receptor 1 activation, we investigated a role for Notch
      signaling in GM-CSF-primed transmigration of human blood eosinophils in vitro and
      in the airway accumulation of mouse eosinophils in vivo. RESULTS: Notch receptor
      1 was constitutively active in freshly isolated human blood eosinophils, and
      inhibition of Notch signaling or specific blockade of Notch receptor 1 activation
      during GM-CSF priming impaired priming-enhanced eosinophil transendothelial
      migration in vitro. Inclusion of Notch signaling inhibitors during priming was
      associated with diminished ERK phosphorylation, and ERK-MAPK activation was
      required for GM-CSF priming-induced transmigration. In vivo in mice, eosinophil
      accumulation within allergic airways was impaired following systemic treatment
      with Notch inhibitor, or adoptive transfer of eosinophils treated ex vivo with
      Notch inhibitor. CONCLUSIONS: These data identify Notch signaling as an intrinsic
      pathway central to GM-CSF priming-induced eosinophil tissue migration.

PMID- 25846341
TI  - Erratum to: The Effects of Nandrolone Decanoate Along with Prolonged Low
      Intensity Exercise on Susceptibility to Ventricular Arrhythmias.

PMID- 25846340
TI  - Faster-acting insulin aspart: earlier onset of appearance and greater early
      pharmacokinetic and pharmacodynamic effects than insulin aspart.
AB  - AIMS: To evaluate the pharmacokinetics and pharmacodynamics of faster-acting
      insulin aspart and insulin aspart in a randomized, single-centre, double-blind
      study. METHODS: Fifty-two patients with type 1 diabetes (mean age 40.3 years)
      received faster-acting insulin aspart, insulin aspart, or another faster aspart
      formulation (not selected for further development), each as a single 0.2 U/kg
      subcutaneous dose, under glucose-clamp conditions, in a three-way crossover
      design (3-12 days washout between dosing). RESULTS: Faster-acting insulin aspart
      had a faster onset of exposure compared with insulin aspart, shown by a 57%
      earlier onset of appearance [4.9 vs 11.2 min; ratio 0.43, 95% confidence interval
      (CI) 0.36; 0.51], a 35% earlier time to reach 50% maximum concentration (20.7 vs
      31.6 min; ratio 0.65, 95% CI 0.59; 0.72) and a greater early exposure within 90
      min after dosing. The greatest difference occurred during the first 15 min, when
      area under the serum insulin aspart curve was 4.5-fold greater with faster-acting
      insulin aspart than with insulin aspart. Both treatments had a similar time to
      maximum concentration, total exposure and maximum concentration. Faster-acting
      insulin aspart had a significantly greater glucose-lowering effect within 90 min
      after dosing [largest difference: area under the curve for the glucose infusion
      rate (AUC(GIR), 0-30 min) ratio 1.48, 95% CI 1.13; 2.02] and 17% earlier time to
      reach 50% maximum glucose infusion rate (38.3 vs 46.1 min; ratio 0.83, 95% CI
      0.73; 0.94). The primary endpoint (AUC(GIR, 0-2 h)) was 10% greater for faster
      acting insulin aspart, but did not reach statistical significance (ratio 1.10,
      95% CI 1.00; 1.22). Both treatments had similar total and maximum glucose
      lowering effects, indicating similar overall potency. CONCLUSIONS: Faster-acting
      insulin aspart was found to have earlier onset and higher early exposure than
      insulin aspart, and a greater early glucose-lowering effect, with similar
      potency.

PMID- 25846342
TI  - Protective Effect of Hydroxytyrosol Against Cardiac Remodeling After
      Isoproterenol-Induced Myocardial Infarction in Rat.
AB  - The present study aimed to investigate the cardioprotective effect of
      hydroxytyrosol (HT) against isoproterenol-induced myocardial infarction in rats.
      Male rats were randomly divided into four groups, control, isoproterenol (Isop)
      and pretreated animals with HT in two different doses (2 and 5 mg/kg) orally for
      7 days and intoxicated with isoproterenol (Isop + HT1) and (Isop + HT2) groups.
      Myocardial infarction in rats was induced subcutaneously by isoproterenol (100
      mg/kg, s.c.) at an interval of 24 h on 6th and 7th day. On 8th day,
      electrocardiographic (ECG) pattern, gravimetric and biochemical parameters were
      assessed. Isoproterenol exhibited changes in ECG pattern, including significant
      ST-segment elevation and increase in the serum troponin-T level by 317 % as
      compared to control rats. Moreover, cardiac injury markers (creatine kinase-MB,
      lactate dehydrogenase, alanine aminotransferase) underwent a notable rise in
      serum of infarcted animals. Else, a disturbance in lipids profile and significant
      increase in lipase and angiotensin-converting enzyme (ACE) activities and heart
      weight ratio were observed in isoproterenol group. However, pre- and co-treatment
      with HT (2 and 5 mg/kg) improved the myocardium injury, restored the hemodynamic
      function and inhibited the ACE activity that prevent cardiac hypertrophy and
      remodeling. Overall, these findings demonstrated that HT exerted a potent
      cardioprotective effect against isoproterenol-induced myocardial infarction. 

PMID- 25846343
TI  - Reversal of warfarin anticoagulation for urgent surgical procedures.
AB  - PURPOSE: Patients treated with warfarin for therapeutic anticoagulation present a
      challenge for the perioperative management of urgent and emergent surgery.
      Anticoagulation must be reversed prior to most surgical procedures to prevent
      intraoperative bleeding. The purpose of this module is to review the options for
      urgent reversal of warfarin anticoagulation and the indications for each reversal
      agent. Selection of the appropriate agent is important to reduce unnecessary
      complications of treatment and to achieve optimal reversal of anticoagulation.
      PRINCIPAL FINDINGS: When urgent surgery is required for patients taking warfarin,
      intravenous vitamin K1 should be used for procedures that can be delayed for six
      to 12 hr. Vitamin K1 results in the activation of existing clotting factors
      rather than requiring the synthesis of new proteins, which allows for its
      relatively rapid onset of action. Intravenous vitamin K1 acts more quickly than
      oral administration, with reversal of anticoagulation occurring within six to 12
      hr vs 18-24 hr, respectively. If surgery cannot be delayed, prothrombin complex
      concentrates (PCCs) should be given, and intravenous vitamin K1 should be infused
      concurrently to ensure sustained reversal of anticoagulation. The duration of
      action of both PCCs and plasma is six hours due to the short half-life of factor
      VII. Prothrombin complex concentrates contain small amounts of heparin and are
      contraindicated in patients with heparin-induced thrombocytopenia. Plasma should
      be used only if PCCs are unavailable or are contraindicated. CONCLUSION: Reversal
      of warfarin anticoagulation can be achieved in a safe and timely manner when the
      appropriate agent is selected and administered correctly.

PMID- 25846344
TI  - Celecoxib pharmacogenetics and pediatric adenotonsillectomy: a double-blinded
      randomized controlled study.
AB  - BACKGROUND: Pediatric adenotonsillectomy (A&T) is associated with prolonged pain
      and functional limitation. Celecoxib is an effective analgesic in adult surgery
      patients; however, its analgesic efficacy on pain and functional recovery in
      pediatric A&T patients is unknown. METHODS: During 2009-2012, children (age 2-18
      yr) scheduled for elective A&T were enrolled in a single-centre double-blind
      randomized controlled trial. Study participants received either oral placebo or
      celecoxib 6 mg.kg(-1) preoperatively, followed by 3 mg.kg(-1) twice daily for
      five doses. The primary outcome was the mean "worst 24-hr pain" scores during
      postoperative days (PODs) 0-2 on a 100-mm visual analogue scale (VAS). Secondary
      outcomes for PODs 0-7 included co-analgesic consumption, adverse events, and
      functional recovery. The impact of the CYP2C9*3 allele - associated with reduced
      celecoxib hepatic metabolism - on recovery was considered. RESULTS: Of the 282
      children enrolled, 195 (celecoxib = 101, placebo = 94) were included in the
      primary outcome analysis. While on treatment, children receiving celecoxib
      experienced a modest reduction in the average pain experienced over PODs 0-2 (7
      mm on a VAS; 95% confidence interval [CI]: 0.3 to 14; P = 0.04) and a "clinically
      significant" reduction (>= 10 mm on a VAS; P <= 0.01) on PODs 0 and 1. During
      PODs 0-2, the mean acetaminophen consumption was lower in the celecoxib group vs
      the placebo group (78 mg.kg(-1); 95% CI: 68 to 89 vs 97 mg.kg(-1); 95% CI: 85 to
      109, respectively; P = 0.03). No differences in adverse events, functional
      recovery, or satisfaction were observed by POD 7. The CYP2C9*3 allele was
      associated with less pain and improved functional recovery. CONCLUSIONS: A three
      day course of oral celecoxib reduces early pain and co-analgesic consumption;
      however, an increase in dose, dose frequency, and duration of dose may be
      required for sustained pain relief in the pediatric setting. The CYP2C9*3 allele
      may influence recovery. This trial was registered at: ClinicalTrials.gov:
      NCT00849966.

PMID- 25846345
TI  - Functional brain development in growth-restricted and constitutionally small
      fetuses: a fetal magnetoencephalography case-control study.
AB  - OBJECTIVE: Fetal magnetoencephalography records fetal brain activity non
      invasively. Delayed brain responses were reported for fetuses weighing below the
      tenth percentile. To investigate whether this delay indicates delayed brain
      maturation resulting from placental insufficiency, this study distinguished two
      groups of fetuses below the tenth percentile: growth-restricted fetuses with
      abnormal umbilical artery Doppler velocity (IUGR) and constitutionally small-for
      gestational-age fetuses with normal umbilical artery Doppler findings (SGA) were
      compared with fetuses of adequate weight for gestational age (AGA), matched for
      age and behavioural state. DESIGN: A case-control study of matched pairs.
      SETTING: Fetal magnetoencephalography-Center at the University Hospital of
      Tuebingen. POPULATION: Fourteen IUGR fetuses and 23 SGA fetuses were matched for
      gestational age and fetal behavioural state with 37 healthy, normal-sized
      fetuses. METHODS: A 156-channel fetal magentoencephalography system was used to
      record fetal brain activity. Light flashes as visual stimulation were applied to
      the fetus. The Student's t-test for paired groups was performed. MAIN OUTCOME
      MEASURE: Latency of fetal visual evoked magnetic responses (VER). RESULTS: The
      IUGR fetuses showed delayed VERs compared with controls (IUGR, 233.1 ms;
      controls, 184.6 ms; P = 0.032). SGA fetuses had similar evoked response latencies
      compared with controls (SGA, 216.1 ms; controls, 219.9 ms; P = 0.828).
      Behavioural states were similarly distributed. CONCLUSION: Visual evoked
      responses are delayed in IUGR fetuses, but not in SGA. Fetal behavioural state as
      an influencing factor of brain response latency was accounted for in the
      comparison. This reinforces that delayed brain maturation is the result of
      placental insufficiency.

PMID- 25846346
TI  - Characterization of two novel HLA-A null alleles: A*11:210N and A*26:107N.
AB  - Two new HLA-A null alleles were characterized, A*11:210N and A*26:107N. 

PMID- 25846347
TI  - Effect of visco-elastic silk-chitosan microcomposite scaffolds on matrix
      deposition and biomechanical functionality for cartilage tissue engineering.
AB  - Commonly used polymer-based scaffolds often lack visco-elastic properties to
      serve as a replacement for cartilage tissue. This study explores the effect of
      reinforcement of silk matrix with chitosan microparticles to create a visco
      elastic matrix that could support the redifferentiation of expanded chondrocytes.
      Goat chondrocytes produced collagen type II and glycosaminoglycan (GAG)-enriched
      matrix on all the scaffolds (silk:chitosan 1:1, 1:2 and 2:1). The control group
      of silk-only constructs suffered from leaching out of GAG molecules into the
      medium. Chitosan-reinforced scaffolds retained a statistically significant (p <
      0.02) higher amount of GAG, which in turn significantly increased (p < 0.005) the
      aggregate modulus (as compared to silk-only controls) of the construct akin to
      that of native tissue. Furthermore, the microcomposite constructs demonstrated
      highly pronounced hysteresis at 4% strain up to 400 cycles, mimicking the visco
      elastic properties of native cartilage tissue. These results demonstrated a step
      towards optimizing the design of biomaterial scaffolds used for cartilage tissue
      engineering. Copyright (c) 2015 John Wiley & Sons, Ltd.

PMID- 25846348
TI  - Isolated shoulder weakness as a result of a cortical infarction in the precentral
      gyrus.
AB  - Since its discovery, our understanding of the primary motor cortex has continued
      to evolve. The presentations of rare, isolated, motor palsies of small muscle
      groups have heavily contributed to the characterization of the somatotopic
      representation of the human body on the cortex. We present a case of localized,
      left shoulder small muscle group weakness secondary to ischemic cerebral
      infarction in the primary motor cortex. The patient experienced full recovery
      over several days. Strokes causing isolated shoulder weakness are rare due to the
      relatively small area dedicated to shoulder motor function in the precentral
      gyrus. However, our patient presented with a larger area of infarction than in
      previously reported cases, demonstrating the large individual variability that
      may exist within the motor cortex somatotopic map. 

PMID- 25846349
TI  - TRACER: an 'eye-opener' to the patient experience across the transition of care
      in an internal medicine resident program.
AB  - BACKGROUND: A safe patient transition requires a complex set of physician skills
      within the interprofessional practice. OBJECTIVE: To evaluate a rotation which
      applies self-reflection and workplace learning in a TRAnsition of CarE Rotation
      (TRACER) for internal medicine (IM) residents. TRACER is a 2-week required IM
      resident rotation where trainees join a ward team as a quality officer and follow
      patients into postacute care. METHODS: In 2010, residents participated in
      semistructured, one-on-one interviews as part of ongoing program evaluation. They
      were asked what they had learned on TRACER, the year prior, and how they used
      those skills in their practice. Using transcripts, the authors reviewed and coded
      each transcript to develop themes. RESULTS: Five themes emerged from a
      qualitative, grounded theory analysis: seeing things from the other side, the 'ah
      ha' moment of fragmented care, team collaboration including understanding nursing
      scope of practice in different settings, patient understanding, and passing the
      learning on. TRACER gives residents a moment to breathe and open their eyes to
      the interprofessional practice setting and the patient's experience of care in
      transition. CONCLUSIONS: Residents learn about transitions of care through self
      reflection. This learning is sustained over time and is valued enough to teach to
      their junior colleagues.

PMID- 25846350
TI  - A profile of Latinos with poorly controlled diabetes in South Florida.
AB  - INTRODUCTION: Latinos are the largest minority group in the United States and
      diabetes or pre-diabetes affects more than 70% of Latinos aged 45 years and
      older. Miami-Dade County is home to one of the highest populations of diverse
      Latinos. In this descriptive manuscript, we present baseline characteristics of
      participants enrolled in the Miami Healthy Heart Initiative (MHHI). This was a
      study conducted to determine the effects of a community health worker (CHW)
      intervention among Latinos with poorly controlled diabetes in South Florida.
      METHODS: We recruited 300 diverse Latino adults with suboptimal diabetes outcomes
      (HbA1c>=8) into MHHI. This randomized control trial examined the impact of a 1
      year CHW-led intervention on glycemic control, blood pressure, and cholesterol
      levels. At baseline, physiologic measures, including HbA1c, LDL, blood pressure,
      and BMI, were assessed. Data on socio-demographic characteristics and additional
      determinants of health such as depression status, provider communication, diet,
      exercise, cigarette smoking, readiness to change diabetes management behaviors
      (stages of change), and confidence in ability to improve diabetes self-care (self
      efficacy) were collected. RESULTS: Participants came from 20 different countries,
      with Cuban Americans representing 38% of the sample. Most had lived in the US for
      more than 10 years, had completed at least 12 years of school, and had high
      levels of health literacy, yet 48% had very low acculturation. Nearly 80% had
      poor self-efficacy, 80% met the criteria for depression, and 83% were not
      adherent to their medications. More than half the population was not at their
      target for blood pressure, 50% were above the recommended LDL goal, and most were
      obese. CONCLUSION: In a diverse population of Latinos with poorly controlled
      diabetes in Miami, we found high rates of depression, obesity, medication non
      adherence, poor self-efficacy, and provider communication. These may contribute
      to poor diabetes control, high blood pressure, and elevated cholesterol.

PMID- 25846351
TI  - A case of acute generalized exanthematous pustulosis associated with
      polyarteritis nodosa, responding to systemic steroids.
AB  - A patient with a known biopsy of polyarteritis nodosa diagnosis presented with
      cyclic fevers, acute kidney injury, and progression of rash from macular to
      pustular, worsening despite being on antibiotics, without evidence of infection
      on multiple cultures. The patient had a pathological diagnosis from a skin biopsy
      of acute generalized exanthematous pustulosis syndrome, with a total resolution
      of rash, fevers, and acute kidney injury on treatment with pulse steroids. 

PMID- 25846352
TI  - Acquired tracheoesophageal fistula status post laryngeal neoplasm resection.
AB  - A tracheoesophageal fistula (TEF), albeit rare, can be a life-threatening
      condition that requires prompt identification and treatment. Pulmonary
      contamination and restriction of proper nutrition are common, unfortunate
      consequences of untreated TEFs and are often the causes of mortality in this
      population. In our patient, a history of laryngeal malignancy along with symptoms
      of chest pain and cough with ingestion of liquids, even without evidence of
      aspiration pneumonia, appropriately prompted investigation for potential TEF.
      Initial imaging through barium swallow identified the TEF, and the patient
      underwent treatment with endoclips by endoscopy with bronchoscopic assistance. 

PMID- 25846353
TI  - Modified Early Warning System improves patient safety and clinical outcomes in an
      academic community hospital.
AB  - BACKGROUND AND OBJECTIVE: Severe adverse events such as cardiac arrest and death
      are often heralded by abnormal vital signs hours before the event. This
      necessitates an organized track and trigger approach of early recognition and
      response to subtle changes in a patient's condition. The Modified Early Warning
      System (MEWS) is one of such systems that use temperature, blood pressure, pulse,
      respiratory rate, and level of consciousness with each progressive higher score
      triggering an action. Root cause analysis for mortalities in our institute has
      led to the implementation of MEWS in an effort to improve patient outcomes. Here
      we discuss our experience and the impact of MEWS implementation on patient care
      at our community academic hospital. METHODS: MEWS was implemented in a
      protocolized manner in June 2013. The following data were collected from non-ICU
      wards on a monthly basis from January 2010 to June 2014: 1) number of rapid
      response teams (RRTs) per 100 patient-days (100PD); 2) number of cardiopulmonary
      arrests 'Code Blue' per 100PD; and 3) result of each RRT and Code Blue (RRT
      progressed to Code Blue, higher level of care, ICU transfer, etc.). Overall
      inpatient mortality data were also analyzed. RESULTS: Since the implementation of
      MEWS, the number of RRT has increased from 0.24 per 100PD in 2011 to 0.38 per
      100PD in 2013, and 0.48 per 100PD in 2014. The percentage of RRTs that progressed
      to Code Blue, an indicator of poor outcome of RRT, has been decreasing. In
      contrast, the numbers of Code Blue in non-ICU floors has been progressively
      decreasing from 0.05 per 100PD in 2011 to 0.02 per 100PD in 2013 and 2014. These
      improved clinical outcomes are associated with a decline of overall inpatient
      mortality rate from 2.3% in 2011 to 1.5% in 2013 and 1.2% in 2014. CONCLUSIONS:
      Implementation of MEWS in our institute has led to higher rapid response system
      utilization but lower cardiopulmonary arrest events; this is associated with a
      lower mortality rate, and improved patient safety and clinical outcomes. We
      recommend the widespread use of MEWS to improve patient outcomes.

PMID- 25846354
TI  - Owning our off-ramps.
AB  - In this issue of JCHIMP, Meade et al., publish the results of qualitative
      analysis regarding a second-year rotation in tracing the outcome of discharged
      patients. They report that their residents develop remarkable insights into the
      types of failures and miscommunications that plague our discharge processes. This
      perspective piece places this article in the context of literature seeking to
      understand why these problems are endemic and how we must prioritize efforts to
      address and prevent them. 

PMID- 25846355
TI  - Frank's sign: a potential predictor of cardiovascular disease.

PMID- 25846356
TI  - The Val142Ile transthyretin cardiac amyloidosis: more than an Afro-American
      pathogenic variant.

PMID- 25846357
TI  - Response to letter.

PMID- 25846358
TI  - Initial evaluation of thyroid nodules by primary care physicians and internal
      medicine residents.
AB  - OBJECTIVE: The article studied the knowledge and practice patterns of primary
      care providers and internal medicine residents in their initial evaluation of
      thyroid nodules and determined whether their practice is in accordance with
      published guidelines by the American Thyroid Association and American Association
      of Clinical Endocrinologists. METHOD: A survey was distributed to primary care
      physicians (PCPs) and internal medicine residents at a community hospital in
      Baltimore and a chart review was conducted at the Diabetes and Endocrine Center
      in the same hospital. RESULTS: A total of 47 physicians (70%) responded to the
      survey, 16 PCPs and 33 residents. Most responders (96%) will always obtain a TSH,
      and of these, 21% of PCP and 25% of residents will obtain a TSH without any other
      laboratory work-up. Fifty percent of the physicians (PCP, 75%; resident, 39%)
      will always obtain a thyroid ultrasound (p=0.043). Most physicians (97%) will
      refer for a fine-needle aspiration (FNA) biopsy of a nodule >1 cm. Sixty-two
      percent of the physicians will not put a euthyroid patient on levothyroxine
      suppression therapy. Many physicians (48%) are not aware of the AACE and ATA
      thyroid nodule guidelines. Most physicians (65%) have not read the guidelines. Of
      the 113 charts reviewed, TSH was obtained alone in 40% and with other laboratory
      tests in 74%. Thyroid ultrasound was done in 67%. Only one patient was on
      levothyroxine for levothyroxine suppression therapy. DISCUSSION: Although many
      physicians were not aware of the guidelines, and a small number of physicians
      have read them, many PCP and residents responded in concordance with the
      guidelines in obtaining TSH, an ultrasound, performing FNA biopsy, and not
      providing levothyroxine suppressive therapy in euthyroid patients. No differences
      were found between the responses of PCP and residents except for obtaining an
      ultrasound. Chart review data also showed that majority of tests ordered for non
      toxic thyroid nodule evaluation were in agreement with the guidelines.
      Limitations include low survey response rate among PCPs and that results are from
      one community hospital. CONCLUSION: Our findings from the survey and chart review
      conclude that majority of primary care physicians were initiating the appropriate
      work up of thyroid nodules prior to referral to a specialist.

PMID- 25846359
TI  - Editor's notes.

PMID- 25846360
TI  - Respirator Testing Using Virus Aerosol: Comparison between Viability Penetration
      and Physical Penetration.
AB  - Viability, fluorescence (particle volume), photometric, viral RNA, and particle
      number penetration of MS2 bacteriophage through filter media used in three
      different models of respirators were compared to better understand the
      correlation between viability and physical penetration. Although viability and
      viral RNA penetration were better represented by particle volume penetration than
      particle number penetration, they were several-fold lower than photometric
      penetration, which was partially due to the difference in virus survival between
      upstream and downstream aerosol samples. Results suggest that the current NIOSH
      photometer-based test method can be used as a quick means to roughly
      differentiate respirators with different performance against virus aerosols.

PMID- 25846361
TI  - Demographic and Occupational Differences Between Ethnic Minority Workers Who Did
      and Did Not Complete the Telephone Survey in English.
AB  - BACKGROUND/OBJECTIVES: Limited research indicates that using English language
      only surveys in prevalence studies conducted in the general population or in
      specific ethnic populations may result in unrepresentative samples and biased
      results. In this study, we investigated whether participants from ethnic
      minorities who chose to answer a study interview in a language other than English
      (LOTE) differed from those who completed the interview in English. METHODS: This
      study was conducted within an Australian population-based telephone survey that
      assessed the prevalence of occupational exposure to carcinogens among 749 ethnic
      minority workers. We used modified Poisson regression to determine the factors
      associated with completing the interview in a LOTE. RESULTS: Participants who
      elected to complete the interview in a LOTE differed from those who completed it
      in English on several factors, including sex, country of birth, education,
      occupation, and occupational exposure to carcinogens (40% compared with 29%, P <
      0.01). CONCLUSIONS: The participants who chose to complete the study interview in
      their native language had several demographic differences from those participants
      who completed it in English, and were more likely to be exposed to carcinogens at
      work. Prevalence studies that offer only English language study instruments are
      unlikely to produce representative samples of minority groups, and may therefore
      produce biased results.

PMID- 25846362
TI  - Occupational Exposure to Nano-Objects and Their Agglomerates and Aggregates
      Across Various Life Cycle Stages; A Broad-Scale Exposure Study.
AB  - BACKGROUND: Occupational exposure to manufactured nano-objects and their
      agglomerates, and aggregates (NOAA) has been described in several workplace air
      monitoring studies. However, data pooling for general conclusions and exposure
      estimates are hampered by limited exposure data across the occupational life
      cycle of NOAA and a lack in comparability between the methods of collecting and
      analysing the data. By applying a consistent method of collecting and analysing
      the workplace exposure data, this study aimed to provide information about the
      occupational NOAA exposure levels across various life cycle stages of NOAA in the
      Netherlands which can also be used for multi-purpose use. METHODS: Personal/near
      field task-based exposure data was collected using a multi-source exposure
      assessment method collecting real time particle number concentration, particle
      size distribution (PSD), filter-based samples for morphological, and elemental
      analysis and detailed contextual information. A decision logic was followed
      allowing a consistent and objective way of analysing the exposure data. RESULTS:
      In total, 46 measurement surveys were conducted at 15 companies covering 18
      different exposure situations across various occupational life cycle stages of
      NOAA. Highest activity-effect levels were found during replacement of big bags
      (<1000-76000 # cm(-3)), mixing/dumping of powders manually (<1000-52000 # cm(-3))
      and mechanically (<1000-100000 # cm(-3)), and spraying of liquid (2000-800000 #
      cm(-3)) showing a high variability between and within the various exposure
      situations. In general, a limited change in PSD was found during the activity
      compared to the background. CONCLUSIONS: This broad-scale exposure study gives a
      comprehensive overview of the NOAA exposure situations in the Netherlands and an
      indication of the levels of occupational exposure to NOAA across various life
      cycle of NOAA. The collected workplace exposure data and contextual information
      will serve as basis for future pooling of data and modelling of worker exposure.

PMID- 25846363
TI  - Oxidative Potential of Particles in Different Occupational Environments: A Pilot
      Study.
AB  - The oxidative potential (OP) of particulate matter has been proposed as a
      toxicologically relevant metric. This concept is already frequently used for
      hazard characterization of ambient particles but it is still seldom applied in
      the occupational field. The objective of this study was to assess the OP in two
      different types of workplaces and to investigate the relationship between the OP
      and the physicochemical characteristics of the collected particles. At a toll
      station, at the entrance of a tunnel ('Tunnel' site), and at three different
      mechanical yards ('Depot' sites), we assessed particle mass (PM4 and PM2.5 and
      size distribution), number and surface area, organic and elemental carbon,
      polycyclic aromatic hydrocarbon (PAH), and four quinones as well as iron and
      copper concentration. The OP was determined directly on filters without
      extraction by using the dithiothreitol assay (DTT assay-OP(DTT)). The averaged
      mass concentration of respirable particles (PM4) at the Tunnel site was about
      twice the one at the Depot sites (173+/-103 and 90+/-36 ug m(-3), respectively),
      whereas the OP(DTT) was practically identical for all the sites (10.6+/-7.2 pmol
      DTT min(-1) MUg(-1) at the Tunnel site; 10.4+/-4.6 pmol DTT min(-1) MUg(-1) at
      the Depot sites). The OP(DTT) of PM4 was mostly present on the smallest PM2.5
      fraction (OP(DTT) PM2.5: 10.2+/-8.1 pmol DTT min(-1) MUg(-1); OP(DTT) PM4: 10.5+/
      5.8 pmol DTT min(-1) MUg(-1) for all sites), suggesting the presence of redox
      inactive components in the PM2.5-4 fraction. Although the reactivity was similar
      at the Tunnel and Depot sites irrespective of the metric chosen (OP(DTT) ug(-1)
      or OP(DTT) m(-3)), the chemicals associated with OP(DTT) were different between
      the two types of workplaces. The organic carbon, quinones, and/or metal content
      (Fe, Cu) were strongly associated with the DTT reactivity at the Tunnel site
      whereas only Fe and PAH were associated (positively and negatively, respectively)
      with this reactivity at the Depot sites. These results demonstrate the
      feasibility of measuring of the OP(DTT) in occupational environments and suggest
      that the particulate OP(DTT) is integrative of different physicochemical
      properties. This parameter could be a potentially useful exposure proxy for
      investigating particle exposure-related oxidative stress and its consequences.
      Further research is needed mostly to demonstrate the association of OP(DTT) with
      relevant oxidative endpoints in humans exposed to particles. 

PMID- 25846364
TI  - Pronamide: Human relevance of liver-mediated rat leydig cell tumors.
AB  - Dietary exposure to pronamide resulted in higher incidences of Leydig cell tumors
      (LCT) at 1000ppm in a 2-year cancer bioassay, but there were no testes effects at
      40 or 200ppm, and no testes effects at 12-months at any concentration. A 90-day
      mode-of-action (MoA) study was conducted at concentrations of 0, 200, 1000 and
      2000ppm. Standard parameters and stereological and proliferation analyses of LCs,
      targeted testis and liver gene expression, in vitro metabolism of testosterone by
      liver microsomes, and quantification of serum hormones and testosterone
      metabolites were evaluated. Increased testosterone metabolism due to increases in
      hepatic microsomal activity, alterations in serum hormone levels, and other data
      suggest that LCTs were mediated through a perturbation of the HPG-axis. Data
      suggest that this occurs after a threshold of exposure is reached, indicating a
      nonlinear/threshold dose-response. Pronamide-induced rat LCTs mediated by
      alterations to the HPG-axis have low relevance to humans due to quantitative
      differences in sensitivity between rats and humans to LCTs. Pronamide displayed
      no genotoxicity or direct endocrine effects. A margin of exposure approach for
      risk assessment and derivation of the chronic reference dose based on a point of
      departure of 200ppm is most appropriate and protective of human health. 

PMID- 25846365
TI  - An improved method for the isolation of rat alveolar type II lung cells: Use in
      the Comet assay to determine DNA damage induced by cigarette smoke.
AB  - Smoking is a cause of serious diseases, including lung cancer, emphysema, chronic
      bronchitis and heart disease. DNA damage is thought to be one of the mechanisms
      by which cigarette smoke (CS) initiates disease in the lung. Indeed, CS induced
      DNA damage can be measured in vitro and in vivo. The potential of the Comet assay
      to measure DNA damage in isolated rat lung alveolar type II epithelial cells (AEC
      II) was explored as a means to include a genotoxicity end-point in rodent sub
      chronic inhalation studies. In this study, published AEC II isolation methods
      were improved to yield viable cells suitable for use in the Comet assay. The
      improved method reduced the level of basal DNA damage and DNA repair in isolated
      AEC II. CS induced DNA damage could also be quantified in isolated cells
      following a single or 5 days CS exposure. In conclusion, the Comet assay has the
      potential to determine CS or other aerosol induced DNA damage in AEC II isolated
      from rodents used in sub-chronic inhalation studies.

PMID- 25846366
TI  - Pronamide: Weight of evidence for potential estrogen, androgen or thyroid
      effects.
AB  - Based on the exposure potential to humans and environment, pronamide was one of
      52 chemicals on the first list evaluated under US EPA's Endocrine Disruptor
      Screening Program (EDSP). The purpose of EDSP is to screen chemicals for their
      potential to interact with estrogen-, androgen-, or thyroid-signaling pathways. A
      battery of 11 Tier 1 assays was completed for pronamide in accordance with EDSP
      test guidelines. In addition, Other Scientifically Relevant Information, which
      included existing data from regulatory guideline studies and published
      literature, was used in a weight-of-evidence (WoE) evaluation of potential
      endocrine activity. The WoE conclusion is that pronamide does not interact
      directly with estrogen, androgen, or thyroid receptors or post-receptor events.
      Across in vivo studies, the liver is consistently and reproducibly the target
      organ for pronamide's effects. Pronamide activates hepatocytic nuclear receptors
      (including constitutive androstane receptor), induces hepatic enzymes, produces
      hepatocellular hypertrophy and increases liver weights. These changes are coupled
      with increased metabolic activity and a subsequent increased metabolism and/or
      clearance of both steroid and thyroid hormones. Thus, while pronamide alters some
      endocrine-sensitive endpoints in EDSP Tier 1 assays, effects on liver metabolism
      likely explain altered hormone levels and indirect endocrine changes. 

PMID- 25846367
TI  - Relevance of the mouse skin initiation-promotion model for the classification of
      carcinogenic substances encountered at the workplace.
AB  - The Permanent Senate Commission for the Investigation of Health Hazards of
      Chemical Compounds in the Work Area (MAK Commission of the Deutsche
      Forschungsgemeinschaft) evaluates chemical substances using scientific criteria
      to prevent adverse effects on health at the work place. As part of this task
      there is a need to evaluate tumor promoting activity of chemicals (enhancement of
      formation of squamous cell carcinomas via premalignant papillomas) obtained from
      two-stage initiation/promotion experiments using the mouse skin model. In the
      present communication we address this issue by comparing responses seen in mouse
      skin with those in humans. We conclude that tumor promotional effects seen in
      such animal models be carefully analyzed on a case by case basis. Substances that
      elicit a rather non-specific effect that is restricted to the high dose range are
      considered to be irrelevant to humans and thus do not require classification as
      carcinogens. In contrast, substances that might have both a mode of action and a
      potency similar to the specific effects seen with TPA (12-O-tetradecanoylphorbol
      13-acetate), the prototype tumor promoter in mouse skin, which triggers receptor
      mediated signal cascades in the very low dose range, have to be classified in a
      category for carcinogens. 

PMID- 25846368
TI  - Elevated tissue Cr levels, increased plasma oxidative markers, and global
      hypomethylation of blood DNA in male Sprague-Dawley rats exposed to potassium
      dichromate in drinking water.
AB  - Hexavalent chromium [Cr (VI)] is prevalent in ground water in some areas, but
      evidence on the toxic effects of Cr (VI) via ingestion through drinking water
      remains insufficient. The aims of our study were to investigate the toxic effects
      of Cr (VI) through oral water ingestion on oxidative stress and DNA methylation.
      Thirty-two Sprague-Dawley rats were randomly divided into four groups, and
      exposed to porassium dichromate (K2 Cr2 O7 ; 0, 30, 100, and 300 mg/L) in
      drinking water for 4 weeks. Mean body weight gain, mean water consumption,
      clinical chemistry determinations, and oxidative stress levels in plasma were
      measured. Global DNA methylation changes and DNA methylation status at the
      promoter of p16 gene were also detected. After 4 weeks, mild anemic effects and
      increased plasma malondialdehyde (MDA) levels occurred in rats exposed to 100
      mg/L or 300 mg/L of Cr (VI). Plasma glutathione peroxidase (GSH-Px) activity
      decreased in all exposed groups. Global DNA methylation levels were reduced in
      100 mg/L and 300 mg/L exposure groups. However, DNA methylation status at the
      promoter of P16 gene remained unchanged in all K2 Cr2 O7- treated groups. The
      correlation analysis indicated that increased MDA levels were closely correlated
      to global DNA hypomethylation. Our results indicated that oral ingestion of Cr
      (VI) through drinking water caused not only oxidative stress in plasma, but also
      global DNA hypomethylation in blood cells from male rats, and a good correlation
      was found between increased MDA levels and reduced global DNA methylation. (c)
      2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1080-1090, 2016. 

PMID- 25846369
TI  - A hybrid adsorbent/visible light photocatalyst for the abatement of microcystin
      LR in water.
AB  - A hybrid adsorbent/photocatalyst was obtained and used for the removal of
      microcystin-LR, a potent toxin, from water via adsorption and photocatalyzed
      oxidation with singlet oxygen. The combined adsorption/photooxidation processes
      yielded a 500-fold decrease of the overall MC-LR concentration. The
      adsorbent/photocatalyst can be easily removed from the reaction system by
      sedimentation or centrifugation. 

PMID- 25846370
TI  - Tetranectin positive expression in tumour tissue leads to longer survival in
      Danish women with ovarian cancer. Results from the 'Malova' ovarian cancer study.
AB  - The primary objective of this study was to analyse Tetranectin (TN) expression in
      tumour tissues and TN serum concentration in 758 women with epithelial ovarian
      tumours. The second was to evaluate, whether TN tissue expression levels
      correlate with clinico-pathological parameters and prognosis of the disease.
      Using tissue arrays we analysed the expression levels in tissues from 166 women
      with borderline ovarian tumours (BOTs) and 592 women with ovarian cancer (OC). A
      panel of three antibodies was used for immunohistochemistry: a polyclonal and two
      monoclonal antibodies. Serum TN was measured using the polyclonal antibody A-371.
      Univariate survival analyses stratified for chemotherapy showed that positive
      tissue TN as demonstrated by the polyclonal antibody indicated a significantly
      longer overall survival (OS) (p = 0.0001) as well as cancer specific survival
      (CSS) (p < 0.0001). High serum TN was likewise found to imply longer OS (p <
      0.0001) and CSS (p < 0.0001), whereas tissue staining with the two monoclonal
      antibodies failed to demonstrate any significant correlation with either survival
      type. Univariate Kaplan-Meier survival analysis performed on all OC cases showed
      a significantly longer OS (p = 0.0009) and CSS (p = 0.0006) for women with TN
      positive tumour tissue and in women with high serum TN levels (p < 0.0001 for
      both). However, in the multivariate Cox regression analysis, only serum TN was
      found to be an independent prognostic factor for OS (p = 0.01) and not for CSS (p
      = 0.08). In conclusion, our results predict that a positive TN expression of both
      tumour tissue and serum points to a more favourable outcome for OC patients.

PMID- 25846371
TI  - Photoisomerisation in Aminoazobenzene-Substituted Ruthenium(II) Tris(bipyridine)
      Complexes: Influence of the Conjugation Pathway.
AB  - Transition-metal complexes containing stimuli-responsive systems are attractive
      for applications in optical devices, photonic memory, photosensing, as well as
      luminescence imaging. Amongst them, photochromic metal complexes offer the
      possibility of combining the specific properties of the metal centre and the
      optical response of the photochromic group. The synthesis, the electrochemical
      properties and the photophysical characterisation of a series of donor-acceptor
      azobenzene derivatives that possess bipyridine groups connected to a 4
      dialkylaminoazobenzene moiety through various linkers are presented. DFT and TD
      DFT calculations were performed to complement the experimental findings and
      contribute to their interpretation. The position and nature of the linker
      (ethynyl, triazolyl, none) were engineered and shown to induce different
      electronic coupling between donor and acceptor in ligands and complexes. This in
      turn led to strong modulations in terms of photoisomerisation of the ligands and
      complexes. 

PMID- 25846380
TI  - Interventional MR elastography for MRI-guided percutaneous procedures.
AB  - PURPOSE: MRI-guided thermal ablations require reliable monitoring methods to
      ensure complete destruction of the diseased tissue while avoiding damage to the
      surrounding healthy tissue. Based on the fact that thermal ablations result in
      substantial changes in biomechanical properties, interventional MR elastography
      (MRE) dedicated to the monitoring of MR-guided thermal therapies is proposed
      here. METHODS: Interventional MRE consists of a needle MRE driver, a fast and
      interactive gradient echo pulse sequence with motion encoding, and an inverse
      problem solver in real-time. This complete protocol was tested in vivo on swine
      and the ability to monitor elasticity changes in real-time was assessed in
      phantom. RESULTS: Thanks to a short repetition time, a reduction of the number of
      phase-offsets and the use of a sliding window, one refreshed elastogram was
      provided every 2.56 s for an excitation frequency of 100 Hz. In vivo elastograms
      of swine liver were successfully provided in real-time during one breath-hold.
      Changes of elasticity were successfully monitored in a phantom during its
      gelation with the same elastogram frame rate. CONCLUSION: This study demonstrates
      the ability of detecting elasticity changes in real-time and providing
      elastograms in vivo with interventional MRE that could be used for the monitoring
      of thermal ablations.

PMID- 25846372
TI  - Sialylation regulates brain structure and function.
AB  - Every cell expresses a molecularly diverse surface glycan coat (glycocalyx)
      comprising its interface with its cellular environment. In vertebrates, the
      terminal sugars of the glycocalyx are often sialic acids, 9-carbon backbone
      anionic sugars implicated in intermolecular and intercellular interactions. The
      vertebrate brain is particularly enriched in sialic acid-containing glycolipids
      termed gangliosides. Human congenital disorders of ganglioside biosynthesis
      result in paraplegia, epilepsy, and intellectual disability. To better understand
      sialoglycan functions in the nervous system, we studied brain anatomy, histology,
      biochemistry, and behavior in mice with engineered mutations in St3gal2 and
      St3gal3, sialyltransferase genes responsible for terminal sialylation of
      gangliosides and some glycoproteins. St3gal2/3 double-null mice displayed
      dysmyelination marked by a 40% reduction in major myelin proteins, 30% fewer
      myelinated axons, a 33% decrease in myelin thickness, and molecular disruptions
      at nodes of Ranvier. In part, these changes may be due to dysregulation of
      ganglioside-mediated oligodendroglial precursor cell proliferation. Neuronal
      markers were also reduced up to 40%, and hippocampal neurons had smaller
      dendritic arbors. Young adult St3gal2/3 double-null mice displayed impaired motor
      coordination, disturbed gait, and profound cognitive disability. Comparisons
      among sialyltransferase mutant mice provide insights into the functional roles of
      brain gangliosides and sialoglycoproteins consistent with related human
      congenital disorders.

PMID- 25846381
TI  - Sequence-tagged high-density genetic maps of Zoysia japonica provide insights
      into genome evolution in Chloridoideae.
AB  - Zoysiagrass (Zoysia spp.), belonging to the genus Zoysia in the subfamily
      Chloridoideae, is widely used in domestic lawns, sports fields and as forage. We
      constructed high-density genetic maps of Zoysia japonica using a restriction site
      associated DNA sequencing (RAD-Seq) approach and an F1 mapping population derived
      from a cross between 'Carrizo' and 'El Toro'. Two linkage maps were constructed,
      one for each of the parents. A map consisting of 2408 RAD markers distributed on
      21 linkage groups was constructed for 'Carrizo'. Another map with 1230 RAD
      markers mapped on 20 linkage groups was constructed for 'El Toro'. The average
      distance between adjacent markers of the two maps was at 0.56 and 1.4 cM,
      respectively. Comparative genomics analysis was carried out among zoysiagrass,
      rice and sorghum genomes and a highly conserved collinearity in the gene order
      was observed among the three genomes. Chromosome collinearity was disrupted at
      centromeric regions for each chromosome pair between zoysiagrass and sorghum
      genomes. However, no obvious synteny gaps were observed across the centromeric
      regions between zoysiagrass and rice genomes. Two homologous chromosomes for each
      of the 10 sorghum chromosomes were found in the zoysiagrass genome, indicating an
      allotetraploid origin for zoysiagrass. The reduction of the basic chromosome
      number from 12 to 10 in chloridoids and panicoids took place via independent
      single-step nested chromosome fusion events after the two subfamilies diverged
      from a common ancestor. The genetic maps will assist in genome sequence assembly,
      targeted gene isolation and comparative genomic analyses among grasses.

PMID- 25846382
TI  - Erratum to: Activation of Toll-like receptor 3 increases mouse aortic vascular
      smooth muscle cell contractility through ERK1/2 pathway.

PMID- 25846383
TI  - Housing Satisfaction of Older (55+) Single-Person Householders in U.S. Rural
      Communities.
AB  - This study aims to understand the housing satisfaction of older (55+) single
      person householders in U.S. rural communities using the available variables from
      a secondary data set, the 2011 American Housing Survey (AHS). In this study,
      housing satisfaction was considered to be an indicator of quality of life. Based
      on previous studies, we developed a model to test a hypothesized relationship
      between older (55+) single-person householders' (N = 1,017) housing satisfaction
      and their personal, physical, financial, and environmental characteristics.
      Multiple regression results showed that the model was supported, indicating that
      significant variables in housing satisfaction include age, gender, health status,
      age of house, structure type, and unit location. Among the significant variables,
      health status was revealed to be the strongest factor in housing satisfaction.
      Housing satisfaction was discussed as potential indicators of quality of life.

PMID- 25846384
TI  - Predictors of hypophosphatemia during refeeding of patients with severe anorexia
      nervosa.
AB  - OBJECTIVE: Hypophosphatemia of refeeding is one of the most dangerous
      complications seen during the treatment of patients with anorexia nervosa.
      Although easily detectable and treatable, hypophosphatemia is under-recognized as
      a complication of refeeding. Specific risk factors for the development of
      hypophosphatemia are likely to exist among patients with severe anorexia nervosa.
      The purpose of this study was to identify clinically useful markers that may
      predict the development of or protection from hypophosphatemia during refeeding.
      METHODS: We conducted a retrospective case-control study of 123 patients with
      severe anorexia nervosa admitted for medical stabilization at the ACUTE Center
      for Eating Disorders between October 1, 2008 and December 31, 2013. Risk factors
      for refeeding hypophosphatemia were determined by multivariate logistic
      regression from clinical parameters and laboratory values measured at the time of
      admission. RESULTS: The prevalence of hypophosphatemia was 33.3% (41 of 123
      patients). Higher hemoglobin was the only risk factor associated with a higher
      odds of developing hypophosphatemia (adjusted odds ratio [aOR], 1.56 [95%
      confidence interval [CI], 1.12-2.18]). Statistically significant protective
      factors against the development of hypophosphatemia were observed with higher
      body mass index (aOR, 0.54 [95% CI, 0.39-0.75]), higher serum potassium (aOR,
      0.29 [95% CI, 0.14-0.62]), and higher serum prealbumin (aOR, 0.91 [95% CI, 0.84
      0.99]). DISCUSSION: Four independent factors associated with refeeding
      hypophosphatemia were identified. Identification of findings which correlate with
      hypophosphatemia, or the lack thereof, has the potential to facilitate
      appropriate triage of patients with anorexia nervosa for closer monitoring during
      refeeding.

PMID- 25846385
TI  - Editorial: impaired fasting pyloric compliance in gastroparesis and the benefits
      of therapeutic pyloric dilatation.

PMID- 25846386
TI  - Editorial: impaired fasting pyloric compliance in gastroparesis and the benefits
      of therapeutic pyloric dilatation--authors' reply.

PMID- 25846387
TI  - Letter: portal vein obstruction--which subset of patients could benefit the most?

PMID- 25846388
TI  - Letter: portal vein obstruction--which subset of patients could benefit the most?
      Authors' reply.

PMID- 25846389
TI  - Letter: future directions for epidemiological studies of Barrett's oesophagus.

PMID- 25846390
TI  - Letter: HIV-associated NAFLD--more questions than answers?

PMID- 25846391
TI  - Letter: HIV-associated NAFLD--more questions than answers? Authors' reply.

PMID- 25846392
TI  - Letter: depression and the use of anti-depressants in patients with chronic liver
      disease or liver transplantation.

PMID- 25846393
TI  - Letter: depression and the use of anti-depressants in patients with chronic liver
      disease or liver transplantation - authors' reply.

PMID- 25846394
TI  - Wogonin induces apoptosis and endoplasmic reticulum stress in HL-60 leukemia
      cells through inhibition of the PI3K-AKT signaling pathway.
AB  - Wogonin is a flavonoid isolated from Scutellaria baicalensis root and has
      multiple pharmacological effects, including anticancer effects. Recent studies
      have shown that wogonin induces cell cycle arrest and reverses multi-drug
      resistance in the human K562 leukemia cell line. However, its pharmacological
      function in the apoptosis of leukemia cells remains unknown. Therefore, we
      hypothesized that wogonin can induce apoptosis in the HL-60 leukemia cell line.
      In the present study, the HL-60 cells were treated with different doses of
      wogonin (0-150 uM). Wogonin inhibited the viability of HL-60 cells in a dose
      dependent and time-dependent manner. Flow cytometry and analyses of caspase and
      PARP-1 activation and the Bax/Bcl-2 ratio, demonstrated that the cytotoxic effect
      of wogonin on HL-60 cells was mediated by caspase-dependent and mitochondrial
      dependent apoptosis. Wogonin also induced the expression of certain members of
      the endoplasmic reticulum (ER) stress pathway (CHOP, GRP94 and GRP78) and the
      activation of multiple branches of ER stress transducers (IRE1alpha, PERK
      eIF2alpha and ATF6) in the HL-60 cells. In addition, wogonin reduced the
      phosphorylation of PI3K and AKT in the HL-60 cells. Furthermore, constitutive
      activation of AKT induced by adenoviral vectors inhibited the pro-apoptotic
      effects and ER stress induced by wogonin in the HL-60 cells. In summary, our
      results indicated that wogonin induced apoptosis and ER stress in HL-60 cells,
      which was mediated by the inhibition of the PI3K-AKT signaling pathway.

PMID- 25846395
TI  - Diagnostic utility of measuring free light chains in the cerebrospinal fluid of
      patients with multiple myeloma.

PMID- 25846396
TI  - Intracellular Delivery of Bioactive Cargos to Hard-to-Transfect Cells Using
      Carbon Nanosyringe Arrays under an Applied Centrifugal g-Force.
AB  - There is considerable interest in developing a common, universal platform for
      delivering biomacromolecules such as proteins and RNAs into diverse cells with
      high efficiency. Here, it is shown that carbon nanosyringe arrays (CNSAs) under
      an applied centrifugal g-force (cf-CNSAs) can deliver diverse bioactive cargos
      directly into the cytosol of hard-to-transfect cells with relatively high
      efficiency and reproducibility. The cf-CNSA platform, an optimized version of a
      previous CNSA-mediated intracellular delivery platform that adds a g-force
      feature, exhibits more rapid and superior delivery of cargos to various hard-to
      transfect cells than is the case in the absence of g-force. Active species,
      including small interfering RNAs, plasmids, and proteins are successfully
      transported across plasma membrane barriers into various cells. By overcoming the
      limitations of currently available transfection methods, the cf-CNSA platform
      paves the way to universal delivery of a variety of cargos, facilitating the
      analysis of cellular responses in diverse cell types. 

PMID- 25846397
TI  - Stratified scaffold design for engineering composite tissues.
AB  - A significant challenge to orthopaedic soft tissue repair is the biological
      fixation of autologous or allogeneic grafts with bone, whereby the lack of
      functional integration between such grafts and host bone has limited the clinical
      success of anterior cruciate ligament (ACL) and other common soft tissue-based
      reconstructive grafts. The inability of current surgical reconstruction to
      restore the native fibrocartilaginous insertion between the ACL and the femur or
      tibia, which minimizes stress concentration and facilitates load transfer between
      the soft and hard tissues, compromises the long-term clinical functionality of
      these grafts. To enable integration, a stratified scaffold design that mimics the
      multiple tissue regions of the ACL interface (ligament-fibrocartilage-bone)
      represents a promising strategy for composite tissue formation. Moreover,
      distinct cellular organization and phase-specific matrix heterogeneity achieved
      through co- or tri-culture within the scaffold system can promote biomimetic
      multi-tissue regeneration. Here, we describe the methods for fabricating a tri
      phasic scaffold intended for ligament-bone integration, as well as the tri
      culture of fibroblasts, chondrocytes, and osteoblasts on the stratified scaffold
      for the formation of structurally contiguous and compositionally distinct regions
      of ligament, fibrocartilage and bone. The primary advantage of the tri-phasic
      scaffold is the recapitulation of the multi-tissue organization across the native
      interface through the layered design. Moreover, in addition to ease of
      fabrication, each scaffold phase is similar in polymer composition and therefore
      can be joined together by sintering, enabling the seamless integration of each
      region and avoiding delamination between scaffold layers. 

PMID- 25846398
TI  - Flow cytometric assays for the study of autophagy.
AB  - The use of flow cytometry to study the autophagic process has recently led to the
      development of numerous assays measuring various aspects of the autophagic
      process. These include the detection of the autophagy marker, the microtubule
      associated protein LC3B, cell cycle analysis of LC3B expression, increase in
      lysosomal mass, as well as organelle specific autophagy and the measurement of
      mitochondrial function. We employed a range of autophagy inducing agents to
      determine the degree of LC3B up-regulation and corresponding cell cycle
      distribution, increase in lysosomal mass and mitochondrial dysfunction, as well
      as the relative preference for the specific type of microautophagy or organelle
      phagy. A variety of autophagy inducing agents were compared these included
      rapamycin, chloroquine, various nutrient starvation treatments on two cell types,
      Jurkat T-cell leukaemia and K562 erythromyeloid leukaemia cell lines. Given that
      numerous autophagy inducing agents cause cell cycle arrest, the cell cycle phase
      distribution was investigated and LC3B antigen was shown to increase as cells
      progressed through the cell cycle. LysoTracker dyes have been previously employed
      to investigate the autophagic process and here the LysoTracker signal increased
      in autophagic cells in relation to controls. Organelle autophagy of mitochondria
      and Endoplasmic Reticulum (ER), termed mitophagy and ER phagy was determined flow
      cytometrically by the employment of organelle mass probes, MitoTracker Green
      (MTG) and ER Tracker Green (ERTG). A modification of the cell cycle analysis
      width and area analysis employed for DNA content determinations was developed to
      show changes in organelle mass on a linear scale. Relative changes in linear
      scaled median fluorescence intensity (MFI) was compared to control cells to
      determine the degree and type of organelle phagy induced by a range of autophagy
      inducing agents and treatments. These flow cytometric organelle phagy and
      lysosome mass assays can be used by researchers to study the autophagic process
      further in terms of cell and mitochondrial functionality over time in a cell
      dependent manner as an adjunct to LC3B measurements. 

PMID- 25846399
TI  - Click-crosslinked injectable hyaluronic acid hydrogel is safe and biocompatible
      in the intrathecal space for ultimate use in regenerative strategies of the
      injured spinal cord.
AB  - Traumatic spinal cord injury (SCI) causes damage and degeneration at and around
      the lesion site resulting in a loss of function. SCI presents a complex
      regenerative problem due to the multiple aspects of growth inhibition and the
      heterogeneity in size, shape and extent of injury. Currently, there is no widely
      accepted treatment strategy available and delivering biomolecules to the central
      nervous system remains a challenge. With a view towards achieving local release,
      we designed a hydrogel that can be injected into the intrathecal space. Here we
      describe the synthesis and characterization of a click-crosslinked hyaluronic
      acid hydrogel and demonstrate controlled in vitro release of bioactive brain
      derived neurotrophic factor. Importantly, we demonstrate that this new hydrogel
      is both biocompatible in the intrathecal space based on immunohistochemistry of
      the host tissue response and safe based on behavioral analysis of locomotor
      function. 

PMID- 25846401
TI  - Papillary fill response in single-tooth implants using abutments of different
      geometry.
AB  - OBJECTIVE: To evaluate the influence of abutment geometry on papillary fill in
      the esthetic zone in a delayed crown protocol. MATERIALS AND METHODS: Twenty-six
      subjects received two non-adjacent endosseous implants in the esthetic zone.
      Functional temporary crowns were installed 17-19 weeks later, using conventional
      (control) and curved (experimental) abutments. The abutments were randomized in
      each patient independently. Final crowns were cemented after 2 months (T0).
      Standard intraoral photographs and radiographs were made to evaluate papillary
      fill after 12 months (T12). The interproximal papilla fill was measured by means
      of the papilla index score (PIS) and related to the maximum bone level between
      the implant and the adjacent root as well as the peri-implant marginal bone level
      at T12, both measured radiographically. RESULTS: No statistically significant
      difference between the experimental and the control group could be demonstrated
      (P = 0.25). Ordinal regression analysis showed a positive correlation between the
      maximum bone level and papilla fill (P < 0.01) and a negative correlation between
      the peri-implant marginal bone level and papilla fill (P < 0.05). CONCLUSION: A
      concave abutment does not exhibit a better fill of the papilla compared with a
      straight abutment in single-tooth implant placement using a delayed protocol in
      the esthetic zone after 12 months of function.

PMID- 25846400
TI  - Extracellular zinc induces phosphoethanolamine addition to Pseudomonas aeruginosa
      lipid A via the ColRS two-component system.
AB  - Gram-negative bacteria survive harmful environmental stressors by modifying their
      outer membrane. Much of this protection is afforded upon remodeling of the lipid
      A region of the major surface molecule lipopolysaccharide (LPS). For example, the
      addition of cationic substituents, such as 4-amino-4-deoxy-L-arabinose (L-Ara4N)
      and phosphoehthanolamine (pEtN) at the lipid A phosphate groups, is often induced
      in response to specific environmental flux stabilizing the outer membrane. The
      work herein represents the first report of pEtN addition to Pseudomonas
      aeruginosa lipid A. We have identified the key pEtN transferase which we named
      EptAPa and characterized its strict activity on only one position of lipid A,
      contrasting from previously studied EptA enzymes. We further show that
      transcription of eptAP a is regulated by zinc via the ColRS two-component system
      instead of the PmrAB system responsible for eptA regulation in E. coli and
      Salmonella enterica. Further, although L-Ara4N is readily added to the same
      position of lipid A as pEtN under certain environmental conditions, ColR
      specifically induces pEtN addition to lipid A in lieu of L-Ara4N when Zn2+ is
      present. The unique, specific regulation of eptAP a transcription and enzymatic
      activity described in this work demonstrates the tight yet inducible control over
      LPS modification in P. aeruginosa. 

PMID- 25846402
TI  - Re-examining the origin and function of liver-resident NK cells.
AB  - Recent studies have identified a population of liver-resident innate lymphoid
      cells (ILCs) that, based on the expression of certain phenotypic markers, were
      termed 'liver-resident NK cells' and considered to be a new subset of
      conventional natural killer (cNK) cells. However, different transcriptional
      networks control the development of liver-resident NK cells and cNK cells and,
      furthermore, these cells exhibit features that characterize mucosal ILC1s. Here,
      we review findings providing insight into the origin, phenotype, and function of
      liver-resident NK cells, and discuss these in the context of the current
      understanding of lineage relations of ILC subsets. We propose that the
      similarities between liver-resident NK cells and mucosal ILC1s should be
      considered when revising the categorization framework for these cells, and
      discuss implications of this revision for other tissue-specific NK cells. 

PMID- 25846403
TI  - First trimester screening for Down syndrome using nuchal translucency, maternal
      serum pregnancy-associated plasma protein A, free-beta human chorionic
      gonadotrophin, placental growth factor, and alpha-fetoprotein.
AB  - OBJECTIVE: The aim of this study was to assess the screening performance for Down
      syndrome using first trimester combined screening (FTS) and two additional
      markers, serum placental growth factor (PlGF) and alpha-fetoprotein (AFP).
      METHODS: This is a retrospective case-control study of 137 pregnancies affected
      by Down syndrome and 684 individually matched unaffected pregnancies. Stored
      serum samples were tested for all four markers, and results were expressed as
      multiples of the gestation-specific median (MoM). Multivariate Gaussian modeling
      was used to calculate risks for different combinations of markers and to predict
      the detection rate (DR) and false positive rate (FPR). The predicted performance
      of enhanced FTS (FTS plus PlGF and AFP) was compared with FTS; the performance
      without nuchal translucency (first trimester quad) was assessed. RESULTS: For
      affected pregnancies, the median PlGF level was 0.622 MoM and median AFP 0.764
      MoM. Adding PlGF and AFP improved the screening performance. At 3% FPR, DR
      increased by 4.4% from 83.8% to 88.2% using enhanced FTS; at 95% DR, FPR
      decreased by 8.3%, from 19.3% to 11.0%. At 3% FPR, DR using first trimester quad
      test was 76.4%. CONCLUSIONS: The performance of FTS can be enhanced by adding
      PlGF and AFP. Even without nuchal translucency, the test would perform well.

PMID- 25846404
TI  - Use of loop-mediated isothermal amplification to detect six groups of pathogens
      causing secondary lower respiratory bacterial infections in horses.
AB  - Microbial substitution occasionally occurs following the administration of
      antimicrobials to horses that have pneumonia or pleuropneumonia. Four specific
      loop-mediated isothermal amplification (LAMP) assays were developed to detect
      some equine respiratory pathogens, namely strains of the Bacteroides-Prevotella
      group, Klebsiella pneumoniae, Stenotrophomonas maltophilia, and Staphylococcus
      aureus. These four LAMP assays and two previously published LAMP assays targeting
      Escherichia coli or Pseudomonas aeruginosa were used on clinical respiratory
      specimens and a high accordance found between the results of the LAMP assays and
      bacterial culture. Use of these LAMP assays could enable rapid detection of
      pathogenic bacteria and swift administration of the appropriate antimicrobials. 

PMID- 25846405
TI  - Crystal structures, phase transitions, and switchable dielectric behaviors:
      comparison of a series of N-heterocyclic ammonium perchlorates.
AB  - Three analogue N-heterocyclic complexes, 1-propyl-1-methylpiperidinium
      perchlorate (, [PMpip][ClO4]), 1-cyanomethyl-1-methylpiperidinium perchlorate (,
      [CMpip][ClO4]), and 1-cyanomethyl-1-methylmorpholinium perchlorate (,
      [CMmor][ClO4]) are identified as phase transition materials displaying switchable
      dielectric behaviors. Despite the common [ClO4](-) anion and the closely related
      cations, compound crystallizes in the orthorhombic space group P212121, but
      compounds and belong to the monoclinic space group P21/n with distinct cell
      dimensions. Compounds , and undergo reversible phase transitions around 199, 387
      and 416 K, respectively, accompanied by notable step-like dielectric anomalies
      which could be switched by the phase transition and be tuned in distinct
      dielectric states. The respective dielectric constants in the high dielectric
      states are 1.2, 2.2 and 3.2 times that in the low dielectric states for compounds
      , and . Generally, these differences in the phase transitions and dielectric
      properties are caused by the distinct molecular structures and hydrogen-bonding
      conformations resulting from the structural variations in the side-chain and the
      ring structure. 

PMID- 25846407
TI  - Identification of the Mamestra configurata (Lepidoptera: Noctuidae) peritrophic
      matrix proteins and enzymes involved in peritrophic matrix chitin metabolism.
AB  - The peritrophic matrix (PM) is essential for insect digestive system physiology
      as it protects the midgut epithelium from damage by food particles, pathogens,
      and toxins. The PM is also an attractive target for development of new pest
      control strategies due to its per os accessibility. To understand how the PM
      performs these functions, the molecular architecture of the PM was examined using
      genomic and proteomic approaches in Mamestra configurata (Lepidoptera:
      Noctuidae), a major pest of cruciferous oilseed crops in North America. Liquid
      chromatography-tandem mass spectrometry analyses of the PM identified 82 proteins
      classified as: (i) peritrophins, including a new class with a CBDIII domain; (ii)
      enzymes involved in chitin modification (chitin deacetylases), digestion (serine
      proteases, aminopeptidases, carboxypeptidases, lipases and alpha-amylase) or
      other reactions (beta-1,3-glucanase, alkaline phosphatase, dsRNase, astacin,
      pantetheinase); (iii) a heterogenous group consisting of polycalin, REPATs,
      serpin, C-Type lectin and Lsti99/Lsti201 and 3 novel proteins without known
      orthologs. The genes encoding PM proteins were expressed predominantly in the
      midgut. cDNAs encoding chitin synthase-2 (McCHS-2), chitinase (McCHI), and beta-N
      acetylglucosaminidase (McNAG) enzymes, involved in PM chitin metabolism, were
      also identified. McCHS-2 expression was specific to the midgut indicating that it
      is responsible for chitin synthesis in the PM, the only chitinous material in the
      midgut. In contrast, the genes encoding the chitinolytic enzymes were expressed
      in multiple tissues. McCHS-2, McCHI, and McNAG were expressed in the midgut of
      feeding larvae, and NAG activity was present in the PM. This information was used
      to generate an updated model of the lepidopteran PM architecture. 

PMID- 25846406
TI  - Notch receptor expression in human brain arteriovenous malformations.
AB  - The roles of the Notch pathway proteins in normal adult vascular physiology and
      the pathogenesis of brain arteriovenous malformations are not well-understood.
      Notch 1 and 4 have been detected in human and mutant mice vascular malformations
      respectively. Although mutations in the human Notch 3 gene caused a genetic form
      of vascular stroke and dementia, its role in arteriovenous malformations
      development has been unknown. In this study, we performed immunohistochemistry
      screening on tissue microarrays containing eight surgically resected human brain
      arteriovenous malformations and 10 control surgical epilepsy samples. The tissue
      microarrays were evaluated for Notch 1-4 expression. We have found that compared
      to normal brain vascular tissue Notch-3 was dramatically increased in brain
      arteriovenous malformations. Similarly, Notch 4 labelling was also increased in
      vascular malformations and was confirmed by western blot analysis. Notch 2 was
      not detectable in any of the human vessels analysed. Using both
      immunohistochemistry on microarrays and western blot analysis, we have found that
      Notch-1 expression was detectable in control vessels, and discovered a
      significant decrease of Notch 1 expression in vascular malformations. We have
      demonstrated that Notch 3 and 4, and not Notch 1, were highly increased in human
      arteriovenous malformations. Our findings suggested that Notch 4, and more
      importantly, Notch 3, may play a role in the development and pathobiology of
      human arteriovenous malformations. 

PMID- 25846408
TI  - Cloning and tissue distribution of appetite-regulating peptides in pirapitinga
      (Piaractus brachypomus).
AB  - Pirapitinga (or red-bellied pacu, Piaractus brachypomus, Characiforme,
      Serrasalmidae) is an economically important South American fish for which the
      endocrine mechanism of the regulation of feeding has never been examined. To
      better understand these mechanisms, cDNAs encoding the appetite-regulating
      peptides orexin, cocaine- and amphetamine-regulated transcript (CART), apelin,
      cholecystokinin (CCK), peptide YY (PYY), leptin and ghrelin were isolated in
      pirapitinga and their mRNA distributions examined in peripheral tissues and
      brain. When compared to other fish, the sequences obtained for all peptides were
      most similar to those of other Characiforme fish (i.e. Mexican cavefish) and
      Siluriformes (catfish) as well as Cypriniformes (i.e. goldfish, zebrafish). All
      peptides were widely expressed within the brain. With the exception of CART,
      which was only expressed in brain, the mRNAs of all peptides were present in
      several peripheral tissues, including gastrointestinal tract, kidneys and gills.
      The widespread and peptide-specific distributions suggest that each peptide might
      have distinct physiological actions in the brain and on peripheral tissues, in
      particular on the gastrointestinal tract, which include feeding regulation. This
      preliminary study opens new avenues for further functional studies on the
      endocrine regulation of feeding in Serrasalmidae fish, including pirapitinga. 

PMID- 25846409
TI  - Idiopathic phrenic neuropathies: A case series and review of the literature.
AB  - INTRODUCTION: Phrenic neuropathies (PNs) are a major cause of dyspnea, orthopnea,
      and hypercapnic respiratory failure. The aim of the study was to obtain
      diagnostic findings, assess therapeutic options, and review outcomes in PN
      patients. METHODS: From 2004 to 2013, patients with PN referred to the author's
      institution were studied using clinical, pulmonary function, and
      electrodiagnostic tests. A PubMed search of published PN reports was also done.
      Unilateral PN (UPN) and bilateral PN (BPN) patients were compared. RESULTS: The
      analysis consisted of 10 UPN and 9 BPN patients seen by the author, plus previous
      reports of 18 UPN and 40 BPN patients. BPN patients were older (in the author's
      series) and were more often hypertensive. They reported pain less often, dyspnea
      and orthopnea more often, and had worse results on pulmonary function tests than
      UPN patients. CONCLUSIONS: UPN and BPN are probably 2 variants of the same,
      immune-mediated focal neuropathy. Electrodiagnosis is a valuable confirmatory
      test for PN.

PMID- 25846411
TI  - Crystal structure of a novel two domain GH78 family alpha-rhamnosidase from
      Klebsiella oxytoca with rhamnose bound.
AB  - The crystal structure of the GH78 family alpha-rhamnosidase from Klebsiella
      oxytoca (KoRha) has been determined at 2.7 A resolution with rhamnose bound in
      the active site of the catalytic domain. Curiously, the putative catalytic acid,
      Asp 222, is preceded by an unusual non-proline cis-peptide bond which helps to
      project the carboxyl group into the active centre. This KoRha homodimeric
      structure is significantly smaller than those of the other previously determined
      GH78 structures. Nevertheless, the enzyme displays alpha-rhamnosidase activity
      when assayed in vitro, suggesting that the additional structural domains found in
      the related enzymes are dispensible for function.

PMID- 25846410
TI  - Obstructive heart defects associated with candidate genes, maternal obesity, and
      folic acid supplementation.
AB  - Right-sided and left-sided obstructive heart defects (OHDs) are subtypes of
      congenital heart defects, in which the heart valves, arteries, or veins are
      abnormally narrow or blocked. Previous studies have suggested that the
      development of OHDs involved a complex interplay between genetic variants and
      maternal factors. Using the data from 569 OHD case families and 1,644 control
      families enrolled in the National Birth Defects Prevention Study (NBDPS) between
      1997 and 2008, we conducted an analysis to investigate the genetic effects of 877
      single nucleotide polymorphisms (SNPs) in 60 candidate genes for association with
      the risk of OHDs, and their interactions with maternal use of folic acid
      supplements, and pre-pregnancy obesity. Applying log-linear models based on the
      hybrid design, we identified a SNP in methylenetetrahydrofolate reductase (MTHFR)
      gene (C677T polymorphism) with a main genetic effect on the occurrence of OHDs.
      In addition, multiple SNPs in betaine-homocysteine methyltransferase (BHMT and
      BHMT2) were also identified to be associated with the occurrence of OHDs through
      significant main infant genetic effects and interaction effects with maternal use
      of folic acid supplements. We also identified multiple SNPs in glutamate-cysteine
      ligase, catalytic subunit (GCLC) and DNA (cytosine-5-)-methyltransferase 3 beta
      (DNMT3B) that were associated with elevated risk of OHDs among obese women. Our
      findings suggested that the risk of OHDs was closely related to a combined effect
      of variations in genes in the folate, homocysteine, or
      glutathione/transsulfuration pathways, maternal use of folic acid supplements and
      pre-pregnancy obesity.

PMID- 25846413
TI  - Does the COPD assessment test (CAT(TM)) questionnaire produce similar results
      when self- or interviewer administered?
AB  - PURPOSE: The COPD assessment test (CAT) is a questionnaire that assesses the
      impact of chronic obstructive pulmonary disease (COPD) on health status, but some
      patients have difficulties filling it up by themselves. We examined whether the
      mode of administration of the Spanish version of CAT (self vs. interviewer)
      influences its scores and/or psychometric properties. METHODS: Observational,
      prospective study in 49 Spanish centers that includes clinically stable COPD
      patients (n = 153) and patients hospitalized because of an exacerbation (ECOPD; n
      = 224). The CAT was self-administered (CAT-SA) or administered by an interviewer
      (CAT-IA) based on the investigator judgment of the patient's capacity. To assess
      convergent validity, the Saint George's Respiratory Disease Questionnaire (SGRQ)
      and the London Chest Activity of Daily Living (LCADL) instrument were also
      administered. Psychometric properties were compared across modes of
      administration. RESULTS: A total of 118 patients (31 %) completed the CAT-SA and
      259 (69 %) CAT-IA. Multiple regression analysis showed that mode of
      administration did not affect CAT scores. The CAT showed excellent psychometric
      properties in both modes of administration. Internal consistency coefficients
      (Cronbach's alpha) were high (0.86 for CAT-SA and 0.85 for CAT-IA) as was test
      retest reliability (intraclass correlation coefficients of 0.83 for CAT-SA and
      CAT-IA). Correlations with SGRQ and LCADL were moderate to strong both in CAT-SA
      and CAT-IA, indicating good convergent validity. Similar results were observed
      when testing longitudinal validity. CONCLUSIONS: The mode of administration does
      not influence CAT scores or its psychometric properties. Hence, both modes of
      administration can be used in clinical practice depending on the physician
      judgment of patient's capacity.

PMID- 25846412
TI  - The Intestinal Gas Questionnaire: development of a new instrument for measuring
      gas-related symptoms and their impact on daily life.
AB  - BACKGROUND: Although gas-related symptoms (GRS) are common and intrusive, there
      are no questionnaires to quantitate this problem. This study aimed to develop an
      instrument to rectify this gap in our knowledge. METHODS: Concepts were initially
      identified from the literature and interviews with gastroenterologists.
      Exploratory one-to-one interviews and focus groups with irritable bowel syndrome
      (IBS) patients (n = 28) and non-IBS subjects (n = 27) with GRS were conducted in
      UK, France, and Spain leading to a conceptual framework for the questionnaire.
      Last, iterative rounds of cognitive debriefing were performed with IBS (n = 16)
      and non-IBS subjects (n = 14). KEY RESULTS: From the first three steps, nine GRS
      (bloating, distension, flatulence, odorous flatulence, difficult gas evacuation,
      stomach rumbling, belching, bad breath, and abdominal movement) were identified
      although abdominal movement was subsequently excluded. Twelve quality of life
      domains affected by these symptoms were identified as: Clothing, emotional,
      physical appearance, diet, daily living, work, social life, physical activity,
      relationships, sex life, sleep, and cognitive function. A 24-h recall for
      symptoms and a 7-day recall for impact assessment were supported by the
      qualitative findings. Cognitive debriefing confirmed the understanding of the
      instrument. Across the three languages, the instrument was conceptually and
      linguistically consistent. CONCLUSIONS & INFERENCES: The International Gas
      Questionnaire is a 2-part instrument, developed rigorously and simultaneously in
      three languages assessing seven symptoms (17 items) and their impact on 12
      domains (26 items) in IBS and general population. It is now undergoing
      psychometric validation and should provide a unique tool for epidemiological
      surveys and clinical trials for developing new treatments for these symptoms.

PMID- 25846414
TI  - Postoperative Atrial Fibrillation Predicts Long-Term Cardiovascular Events after
      Radical Cystectomy.
AB  - PURPOSE: Postoperative atrial fibrillation after radical cystectomy occurs in 2%
      to 8% of cases. Recent evidence suggests that transient postoperative atrial
      fibrillation leads to future cardiovascular events. The long-term cardiovascular
      implications of postoperative atrial fibrillation in patients undergoing radical
      cystectomy are largely unknown. MATERIALS AND METHODS: The Healthcare Cost and
      Utilization Project State Inpatient Databases for California and Florida were
      used to identify patients who underwent radical cystectomy between 2007 and 2010.
      After excluding patients with a history of atrial fibrillation, coronary artery
      disease and/or stroke, patients were matched using propensity scoring on age,
      race, insurance status and preexisting comorbidities. Adjusted Kaplan-Meier time
      to-event analysis and Cox proportional hazards models were used to assess the
      effect of postoperative atrial fibrillation on cardiovascular events (acute
      myocardial infarction and stroke) during postoperative year 1. RESULTS: Radical
      cystectomy was performed in 4,345 patients who met the study inclusion criteria,
      of whom 210 (4.8%) had postoperative atrial fibrillation. There was a
      significantly higher cumulative incidence of cardiovascular events during the
      first postoperative year in patients in whom postoperative atrial fibrillation
      developed (24.8% vs 10.9%, adjusted log rank p=0.007). Cox proportional hazards
      regression demonstrated an increased risk of cardiovascular events in patients
      with postoperative atrial fibrillation (HR 10, p=0.02). CONCLUSIONS: Our results
      demonstrate that patients undergoing radical cystectomy in whom transient
      postoperative atrial fibrillation develops are at significantly increased risk
      for cardiovascular events in the first postoperative year. Physicians should be
      vigilant in assessing postoperative atrial fibrillation, even when transient, and
      establish appropriate followup given the increased risk of cardiovascular
      morbidity.

PMID- 25846415
TI  - Comparative Effectiveness of Targeted vs Empirical Antibiotic Prophylaxis to
      Prevent Sepsis from Transrectal Prostate Biopsy: A Retrospective Analysis.
AB  - PURPOSE: We compared the effectiveness of targeted prophylaxis to the
      effectiveness of empirical prophylaxis for preventing sepsis after transrectal
      prostate biopsy using a retrospective multicenter quality improvement study.
      MATERIALS AND METHODS: A total of 13 Kaiser Permanente urology departments
      participated in a 1-year retrospective analysis of a quality improvement study.
      In the targeted prophylaxis group rectal cultures were performed before
      transrectal prostate biopsy and antibiotic sensitivities of Escherichia coli were
      used to guide the selection of a single agent antibiotic for prophylaxis.
      Cultures were plated on 10 MUg/ml ciprofloxacin infused MacConkey agar at a
      central laboratory. Urologists using empirical prophylaxis continued the usual
      regimen of ciprofloxacin monotherapy prophylaxis but sometimes added an
      additional prophylactic antibiotic. The primary outcome of post-biopsy sepsis was
      compiled by a search of the electronic medical record for the appropriate ICD-9
      codes. RESULTS: A total of 5,355 prostate biopsy procedures were performed
      between May 1, 2013 and April 30, 2014. Targeted prophylaxis was used in 1,802
      procedures (34%) and empirical prophylaxis was used in 3,553 (66%). The overall
      incidence of post-biopsy sepsis was 0.52% (28 of 5,355 cases). The incidence of
      sepsis was 0.44% (8 of 1,802 cases) in the targeted prophylaxis group and 0.56%
      (20 of 3,553) in the empirical prophylaxis group (p = 0.568). The prevalence of
      ciprofloxacin resistant E. coli on rectal culture was 25% (444 of 1,802 cases).
      Seven of the 8 patients (88%) on targeted prophylaxis in whom sepsis developed
      used a prophylactic antibiotic to which the bacteria causing post-biopsy sepsis
      were sensitive. CONCLUSIONS: The targeted prophylaxis protocol enabled physicians
      to avoid using more than 1 broad-spectrum empirical antibiotic while
      simultaneously achieving an overall rate of sepsis similar to the rate seen with
      empirical prophylaxis.

PMID- 25846416
TI  - Oncologic Efficacy of Radio Frequency Ablation for Small Renal Masses: Clear Cell
      vs Papillary Subtype.
AB  - PURPOSE: Current radio frequency ablation series do not distinguish renal cell
      carcinoma subtypes when reporting oncologic efficacy. Papillary neoplasms may be
      more amenable to radio frequency ablation than clear cell carcinoma because they
      are less vascular, which may limit heat energy loss. We report the long-term
      outcomes of patients treated with radio frequency ablation for small renal masses
      by renal cell carcinoma subtype. MATERIALS AND METHODS: The records of patients
      undergoing radio frequency ablation for small renal masses (cT1a) at 2
      institutions from March 2007 to July 2012 were retrospectively reviewed. Patients
      were included in analysis if they had biopsy confirmed clear cell or papillary
      renal cell carcinoma histology. Patients had at least 1 contrast enhanced cross
      sectional image following radio frequency ablation. Demographic data between
      tumor subtypes were compared using the paired t-test. Oncologic outcomes were
      determined by Kaplan-Meier survival analysis and survivor curves were compared
      with the log rank test. RESULTS: A total of 229 patients met study inclusion
      criteria. There were 181 clear cell tumors and 48 papillary tumors. Median
      followup was 33.2 months. There was no difference between tumor groups based on
      patient age, tumor size or grade, or months of followup. Five-year disease-free
      survival was 89.7% for clear cell tumors and 100% for papillary tumors (p =
      0.041). There was no significant difference in overall survival (88.4% vs 89.6%,
      p = 0.764). CONCLUSIONS: Radio frequency ablation outcomes seem to be determined
      in part by renal cell carcinoma subtype with clear cell renal tumors having less
      favorable outcomes. We hypothesize that this is due to differences in tumor
      vascularity. Our experience suggests that future tumor ablation studies should
      consider reporting outcomes based on tumor cell types.

PMID- 25846417
TI  - Outcomes of Ventral Onlay Buccal Mucosa Graft Urethroplasty in Patients after
      Radiotherapy.
AB  - PURPOSE: We evaluated stricture-free survival and functional outcomes of buccal
      mucosa graft urethroplasty in patients with urethral stricture disease after
      radiotherapy. MATERIALS AND METHODS: We reviewed our urethroplasty database for
      patients with a radiotherapy history who underwent buccal mucosa graft
      urethroplasty between January 2009 and October 2013. We reviewed patient charts
      and the institutional, standardized, nonvalidated questionnaires administered to
      each patient postoperatively. Study end points included 1) the success rate, 2)
      continence status, 3) erectile function and 4) patient satisfaction
      postoperatively. Success was defined as stricture-free survival. RESULTS: Of 38
      men included in the study prostate cancer was the most common indication for
      radiotherapy in 35 (92.1%). External beam radiotherapy was performed in 24 cases
      (64.9%), brachytherapy was done in 8 (21.6%) and a combination of the 2
      treatments was performed in 6 (13.5%). Strictures were in the
      bulbar/bulbomembranous urethra and had a median length of 3.0 cm (range 1.0 to
      8.0). The overall success rate was 71.1% at a median followup of 26.5 months
      (range 1.0 to 50.0). Median time to stricture recurrence was 17.0 months (range
      3.0 to 44.0). De novo urinary incontinence was observed in 4 patients (10.5%).
      Erectile function remained mostly unchanged compared to preoperative status.
      Study limitations include the small sample size and the lack of validated
      questionnaires. CONCLUSIONS: At short-term to mid-term followup the success rate
      of ventral onlay buccal mucosa graft urethroplasty in patients with radiotherapy
      history seems acceptable. However, patients must be counseled about the increased
      risk of urinary incontinence. Longer followup is warranted to address long-term
      outcomes.

PMID- 25846418
TI  - Disparities in the Use of Sacral Neuromodulation among Medicare Beneficiaries.
AB  - PURPOSE: Sacral neuromodulation with the InterStim(r) has been done to treat
      urinary and bowel control. There are limited data in the literature on use trends
      of sacral neuromodulation. We explored disparities in use among Medicare
      beneficiaries. MATERIALS AND METHODS: We queried a 5% national random sample of
      Medicare claims for 2001, 2004, 2007 and 2010. All patients with an ICD-9
      diagnosis code representing a potential urological indication for sacral
      neuromodulation were included. Patients who underwent device implantation were
      identified using CPT-4 codes. Statistical analysis was done with the chi-square
      and Fisher tests, and multivariate logistic regression using software. RESULTS: A
      total of 2,322,060 patients were identified with a diagnosis that could
      potentially be treated with sacral neuromodulation. During the 10-year study
      period the percent of these patients who ultimately underwent implantation
      increased from 0.03% to 0.91% (p <0.0001) for a total of 13,360 (0.58%). On
      logistic regression analysis women (OR 3.85, p <0.0001) and patients younger than
      65 years (OR 1.00 vs 0.29 to 0.39, p <0.0001) were more likely to be treated.
      Minority patients (OR 0.38, p <0.0001) and those living in the western United
      States (OR 0.52, p <0.0001) were less likely to receive treatment. CONCLUSIONS:
      Sacral neuromodulation use significantly increased among Medicare beneficiaries
      in a 10-year period. Patients were more likely to be treated with sacral
      neuromodulation if they were female, white, younger (younger than 65 years) and
      living outside the western United States.

PMID- 25846419
TI  - Lamin A/C Acts as an Essential Factor in Mesenchymal Stem Cell Differentiation
      Through the Regulation of the Dynamics of the Wnt/beta-Catenin Pathway.
AB  - Changes in the expression of lamin A/C, a fibrilar protein of the nuclear
      envelope, are associated with the cellular features of age-related bone loss.
      Reduced expression of lamin A/C inhibits osteoblastogenesis while facilitating
      adipogenic differentiation of mesenchymal stem cells (MSC) in vitro and in vivo.
      In this study we investigated the regulatory role that lamin A/C plays on the
      essential elements of the Wnt/beta-catenin pathway, which are pivotal in MSC
      differentiation. Initially, we assessed the effect of lamin A/C gene (LMNA)
      overexpression on MSC differentiation while compared it to lamin A/C depleted
      MSC. Osteogenesis and gene expression of osteogenic factors were higher in LMNA
      transfected MSC as compared to control. Conversely, adipogenesis and expression
      of adipogenic factors were significantly lower in LMNA transfected cells. Nuclear
      beta-catenin was significantly higher (~two fold) in MSC expressing higher levels
      of LMNA as compared to control with nuclear beta-catenin levels being
      significantly lower (~ -42%) in siRNA-treated MSC. Luciferase activity for beta
      catenin-mediated transcriptional activation was significantly higher in cells
      overexpressing LMNA. These data indicate that MSC overexpressing LMNA have higher
      osteogenic and lower adipogenic differentiation potential. In conclusion, our
      studies demonstrate that lamin A/C plays a significant role in the
      differentiation of both osteoblasts and adipocytes by regulating some of the
      elements of Wnt/beta-catenin signaling during early MSC differentiation.

PMID- 25846420
TI  - The cost of errors: Perceived error detection in dual-task conditions.
AB  - Detecting that an error has been made can be crucial for the implementation of
      appropriate behavioral adjustments. Brain imaging studies indicate that error
      detection is not limited to response errors and that similar mechanisms are
      engaged even when behavioral control is not needed. The current study examines
      whether perceived error detection - the detection of erroneous stimuli that
      violate our expectations - requires central resources. In two experiments - using
      a dual-task design - we show that perceived error detection in the first task
      creates a bottleneck in information processing and delays the response selection
      of the second task. The results suggest that the requirement for central
      cognitive resources is a general feature of error detection because it is present
      even when the demand for behavioral control is low. 

PMID- 25846422
TI  - Accumulation of cell-penetrating peptides in large unilamellar vesicles: A
      straightforward screening assay for investigating the internalization mechanism.
AB  - The internalization of cell-penetrating peptides (CPPs) into liposomes (large
      unilamellar vesicles, LUVs) was studied with a rapid and robust procedure based
      on the quenching of a small fluorescent probe, 7-nitrobenz-2-oxa-1,3-diazole
      (NBD). Quenching can be achieved by reduction with dithionite or by pH jump. LUVs
      with different compositions of phospholipids (PLs) were used to screen the
      efficacy of different CPPs. In order to "validate" the composition of the
      membrane models, a control cationic peptide, which does not enter eukaryotic
      cells, was included in the study. It was found that pure DOPG or DOPG within
      ternary mixtures with cholesterol are the most appropriate models for studying
      CPP translocation. An anionic lipid, such as DOPG, is required for the adsorption
      of the basic peptides on the surface of LUVs. In addition, it acts as transfer
      agent through the lipid bilayer. A fluid phase and/or the presence of phase
      defects also appear mandatory for the internalization to occur. The
      neutralization of charges within an inverted micelle demonstrated in the case of
      DOPG and also proposed for a ternary mixture of PLs might not be the only
      mechanism for the CPP translocation. Finally, it is shown that oleic acid
      facilitates the entry inside LUVs in gel phase of a series of cationic peptides
      including CPPs and also the negative control peptide PKCi.

PMID- 25846421
TI  - Lymph node status in inflammatory breast cancer.
AB  - Positive lymph node status in breast cancer is known to be an adverse prognostic
      factor, but the effect of lymph node (LN) status in inflammatory breast cancer
      (IBC) has not been evaluated. This study was designed to investigate the
      association between lymph node status and overall survival (OS) in individuals
      with IBC. Using the Surveillance, Epidemiology, and End Results (SEER) 18
      registry, we collected data on 761 patients diagnosed with non-metastatic IBC
      from 2004 to 2008. Survival analysis was performed using the Kaplan-Meier method.
      Cox proportional hazard regression was performed to evaluate univariate and
      multivariate associations between estrogen and progesterone receptor (ER/PR)
      status, treatment, and OS. Positive nodal status was associated with a
      significant decrease in OS (p < 0.001). Five-year survival for LN-positive and LN
      negative patients was 49 and 66 %, respectively. In node-positive patients, ER or
      PR positivity was associated with improved OS, (p = 0.025, p = 0.007). In node
      positive patients, the combination of surgery and radiation therapy improved OS
      when compared with surgery alone (p = 0.002). Nearly 80 % of the patients in this
      study had nodal metastasis. Positive nodal status was found to be an adverse
      prognostic factor. ER/PR positivity and treatment with surgery and radiation in
      node-positive patients was found to improve outcomes. Further studies are
      required to characterize the biology of IBC and guide the optimal treatment of
      this disease. 

PMID- 25846426
TI  - Is drug insurance status an effect modifier in epidemiologic database studies?
      The case of maternal asthma and major congenital malformations.
AB  - BACKGROUND: Our previous work on the association between maternal asthma and
      congenital malformations was based on cohorts formed by women with public drug
      insurance, i.e., over-represented by women with lower socioeconomic status,
      questioning the generalizability of our findings. This study aimed to evaluate
      whether or not drug insurance status, as a proxy of socioeconomic status, is an
      effect modifier for the association between maternal asthma and major congenital
      malformations. METHODS: A cohort of 36,587 pregnancies from asthmatic women and
      198,935 pregnancies from nonasthmatic women selected independently of their drug
      insurance status was reconstructed with Quebec administrative databases (1998
      2009). Asthmatic women were identified using a validated case definition of
      asthma. Cases of major congenital malformations were identified using diagnostic
      codes recorded in the hospitalization database. Drug insurance status at the
      beginning of pregnancy was classified into three groups: publicly insured with
      social welfare, publicly insured without social welfare, and privately insured.
      Adjusted odds ratios were estimated with generalized estimation equations,
      including an interaction term between maternal asthma and drug insurance status.
      RESULTS: The prevalence of congenital malformations was 6.8% among asthmatic
      women and 5.8% among nonasthmatics. The impact of asthma on the prevalence of
      congenital malformations was significantly greater in women publicly insured with
      social welfare (odds ratio = 1.42; 95% confidence interval, 1.25-1.61) than in
      the other two groups ([odds ratio = 1.10; 1.00-1.21] in the publicly insured
      without social welfare and [odds ratio = 1.13; 1.07-1.20] in the privately
      insured group). CONCLUSION: The increased risk of major congenital malformation
      associated with asthma was significantly higher among pregnant women publicly
      insured with social welfare than among those privately insured. As a result of
      this effect modification by drug insurance status, findings from Quebec
      observational studies using databases mainly formed of patients publicly insured
      with social welfare may not be generalized to the entire population.

PMID- 25846425
TI  - Downregulation of inhibitor of apoptosis-stimulating protein of p53 inhibits
      proliferation and promotes apoptosis of gastric cancer cells.
AB  - Gastric cancer (GC) remains one of the leading causes of cancer-associated
      mortality. Inhibitor of apoptosis-stimulating protein of p53 (iASPP) is a member
      of the inhibitory apoptosis-stimulating protein p53 family. The overexpression of
      iASPP has been detected in several types of tumor in humans. However, the role of
      iASPP in GC remains to be elucidated. The objectives of the present study were to
      detect the expression of iASPP in GC and examine the potential role of iASPP in
      GC cell lines. Using reverse transcription-quantitative polymerase chain reaction
      and western blot analyses, it was identified that the expression of iASPP in GC
      tissues and GC cell lines was higher compared with that in adjacent normal
      tissues and in a normal gastric mucosa cell line (GES-1). To examine the role of
      iASPP in GC cells, the expression of iASPP was inhibited using a small
      interfering (si)RNA against iASPP and it was observed that iASPP expression was
      significantly downregulated. Using MTT assays, colony-formation assays and flow
      cytometry, it was identified that the inhibition of iASPP was able to
      significantly inhibit the proliferation and colony forming ability and promote
      apoptosis in GC cells. To examine the role of iASPP in GC cells in vivo, GC
      cells, which were infected with iASPP-siRNA or control-siRNA were subcutaneously
      injected into nude mice. It was identified that downregulation of iASPP
      significantly inhibited tumor growth in vivo. Thus, iASPP may be a potential
      molecular target in GC therapy.

PMID- 25846427
TI  - NRF2/KEAP1 and Wnt/beta-catenin in the multistep process of liver carcinogenesis
      in humans and rats.

PMID- 25846433
TI  - Posaconazole liquid suspension in solid organ transplant recipients previously
      treated with voriconazole.
AB  - BACKGROUND: Posaconazole (PCZ) has become an attractive alternative to
      voriconazole (VCZ) in transplant recipients with suspected or proven invasive
      filamentous fungal infections, causing fewer drug interactions. Here, we describe
      our experience with PCZ after VCZ in solid organ transplant (SOT) recipients.
      METHODS: VCZ was replaced by PCZ liquid solution in 19 SOT recipients (15 lung, 2
      kidney, 1 liver, and 1 heart/lung) with invasive pulmonary aspergillosis (12/19;
      63.2%), possible invasive pulmonary fungal infection (2/19; 10.5%), prophylaxis
      (2/19; 10.5%), or pulmonary scedosporiosis, mucormycosis, and mixed fungal
      species (1 each). Rationales for switch were suspected adverse reactions to VCZ
      (17/19; 89.4%) and desire to broaden spectrum of coverage to include agents of
      mucormycosis (3/19; 15.8%). RESULTS: PCZ was well tolerated in all patients. In
      those patients with baseline liver enzyme abnormalities, a median change occurred
      in concentrations of alanine transaminase (-20 IU/L), aspartate aminotransferase
      (-17.5 IU/L), and alkaline phosphatase (-61.5 IU/L). Clinical success
      (resolution, stabilization, or prevention of infection) was achieved in 16/19
      (84%) people. CONCLUSION: PCZ appears to have a reasonable safety and
      tolerability profile and may be an effective alternative in SOT patients who
      require an agent with anti-mold activity, but are unable to tolerate VCZ.

PMID- 25846434
TI  - Sucrose-induced analgesia during early life modulates adulthood learning and
      memory formation.
AB  - This study is aimed at examining the long-term effects of chronic pain during
      early life (postnatal day 0 to 8weeks), and intervention using sucrose, on
      cognitive functions during adulthood in rats. Pain was induced in rat pups via
      needle pricks of the paws. Sucrose solution or paracetamol was administered for
      analgesia before the paw prick. Control groups include tactile stimulation to
      account for handling and touching the paws, and sucrose alone was used. All
      treatments were started on day one of birth and continued for 8weeks. At the end
      of the treatments, behavioral studies were conducted to test the spatial learning
      and memory using radial arm water maze (RAWM), as well as pain threshold via foot
      withdrawal response to a hot plate apparatus. Additionally, the hippocampus was
      dissected, and blood was collected. Levels of neurotrophins (BDNF, IGF-1 and NT
      3) and endorphins were assessed using ELISA. The results show that chronic
      noxious stimulation resulted in comparable foot-withdrawal latency between
      noxious and tactile groups. On the other hand, pretreatment with sucrose or
      paracetamol increased pain threshold significantly both in naive rats and
      noxiously stimulated rats (P<0.05). Chronic pain during early life impaired short
      term memory, and sucrose treatment prevented such impairment (P<0.05). Sucrose
      significantly increased serum levels of endorphin and enkephalin. Chronic pain
      decreased levels of BDNF in the hippocampus and this decrease was prevented by
      sucrose and paracetamol treatments. Hippocampal levels of NT-3 and IGF-1 were not
      affected by any treatment. In conclusion, chronic pain induction during early
      life induced short memory impairment, and pretreatment with sucrose prevented
      this impairment via mechanisms that seem to involve BDNF. As evident in the
      results, sucrose, whether alone or in the presence of pre-noxious stimulation,
      increases pain threshold in such circumstances; most likely via a mechanism that
      involves an increase in endogenous opioids. 

PMID- 25846435
TI  - Male song quality modulates c-Fos expression in the auditory forebrain of the
      female canary.
AB  - In canaries, specific phrases of male song (sexy songs, SS) that are difficult to
      produce are especially attractive for females. Females exposed to SS produce more
      copulation displays and deposit more testosterone into their eggs than females
      exposed to non-sexy songs (NS). Increased expression of the immediate early genes
      c-Fos or zenk (a.k.a. egr-1) has been observed in the auditory forebrain of
      female songbirds hearing attractive songs. C-Fos immunoreactive (Fos-ir) cell
      numbers were quantified here in the brain of female canaries that had been
      collected 30min after they had been exposed for 60min to the playback of SS or NS
      or control white noise. Fos-ir cell numbers increased in the caudomedial
      mesopallium (CMM) and caudomedial nidopallium (NCM) of SS birds as compared to
      controls. Song playback (pooled SS and NS) also tended to increase average Fos-ir
      cell numbers in the mediobasal hypothalamus (MBH) but this effect did not reach
      full statistical significance. At the individual level, Fos expression in CMM was
      correlated with its expression in NCM and in MBH but also with the frequency of
      calls that females produced in response to the playbacks. These data thus
      indicate that male songs of different qualities induce a differential metabolic
      activation of NCM and CMM. The correlation between activation of auditory regions
      and of the MBH might reflect the link between auditory stimulation and changes in
      behavior and reproductive physiology. 

PMID- 25846436
TI  - Effect of pentobarbital and isoflurane on acute stress response in rat.
AB  - BACKGROUND: Anesthesia administration before sacrificing animals is a common
      practice in stress-related studies, but the effect of anesthesia on the results
      remains understudied. We aimed to reveal the interference of different
      anesthetics, i.e. intraperitoneal (i.p.) sodium-pentobarbital injection or
      isoflurane inhalation, with the acute stress responses in rats. METHODS: Rats
      were randomly divided into foot shock (FS) and non-stressed control groups, and
      further grouped according to the sacrificing procedure: direct decapitation,
      decapitation after i.p. sodium-pentobarbital injection, or isoflurane inhalation.
      There was also a non-stressed group sacrificed by decapitation following i.p.
      saline injection. Plasma levels of corticosterone (CORT), testosterone and
      estradiol, hypothalamic stress-related molecule mRNA expression of corticotropin
      releasing hormone, arginine vasopressin and oxytocin, and frontal lobe stress
      related molecule mRNA expression of NMDA receptor subunit NR2B, GABAA receptor
      and the neuronal-type nicotinic acetylcholine receptor were measured. RESULTS: FS
      significantly increased plasma CORT levels in direct decapitation and isoflurane
      groups, while this stress response 'disappeared' following i.p. sodium
      pentobarbital injection. In control animals, both the injection of saline and
      pentobarbital caused a significant increase of plasma CORT. Neither the sex
      hormone levels nor the mRNA expression of stress-related molecules in the brain
      showed significant differences among the groups. CONCLUSION: The injection of the
      anesthetic compound rather than the compound itself may cause extra stress which
      interferes with the plasma CORT levels, but not with plasma sex hormone levels
      nor with the brain mRNA expression. Isoflurane inhalation leaves the stress
      response intact and is also optimal from an ethical point of view.

PMID- 25846437
TI  - Development and validation of a tool incorporating cervical length and
      quantitative fetal fibronectin to predict spontaneous preterm birth in
      asymptomatic high-risk women.
AB  - OBJECTIVE: To develop a predictive tool for spontaneous preterm birth (sPTB) in
      asymptomatic high-risk women that includes quantification of fetal fibronectin
      (fFN) along with cervical length (CL) measurement and other clinical factors.
      METHODS: Data were analyzed that had been collected prospectively from 1249 women
      at high risk for sPTB attending preterm surveillance clinics. Clinicians were
      blinded to quantitative measurements of fFN (qfFN), although they were aware of
      qualitative fFN results. Parametric survival models for sPTB, with time-updated
      covariates, were developed and the best was selected using the Akaike and
      Bayesian information criteria. The model was developed on the first 624
      consecutive women and validated on the subsequent 625. Fractional polynomials
      were used to accommodate possible non-linear effects of qfFN and CL. The
      estimated probability of delivery before 30, 34 or 37 weeks' gestation and within
      2 or 4 weeks of testing was calculated for each patient and analyzed as a
      predictive test for the actual occurrence of each event. Predictive statistics
      were calculated to compare training and validation sets. RESULTS: The final model
      that was selected used a log-normal survival curve with CL, ?qfFN and previous
      sPTB/preterm prelabor rupture of membranes as predictors. Predictive statistics
      were similar for training and validation sets. Areas under the receiver-operating
      characteristics curves ranged from 0.77 to 0.99, indicating accurate prediction
      across all five delivery outcomes. CONCLUSIONS: sPTB in high-risk asymptomatic
      women can be predicted accurately using a model combining qfFN and CL, which
      supersedes the single-threshold fFN test, demographic information and obstetric
      history. This algorithm has been incorporated into an App (QUiPP) for widespread
      use.

PMID- 25846438
TI  - [Central nervous system vasculitis according to the 2012 revise international
      Chapel Hill consensus conference nomenclature of vasculitides].
AB  - Vasculitis can be primarily or secondarily to various underlying diseases. It
      frequently affects the nervous system, and neurological deficits may remain even
      after disease remission. Because the progression of vasculitides is usually acute
      to subacute, early initiation of treatment is important from the viewpoint of
      patients' functional status. However, early diagnosis may be difficult,
      particularly in patients with central nervous system vasculitis. Hence, it is
      important to understand the wide-ranging clinical manifestations of vasculitides.
      Here, we summarize the 2012 revised International Chapel Hill Consensus
      Conference nomenclature of vasculitides from the standpoint of central nervous
      system vasculitis. 

PMID- 25846439
TI  - [Diagnostic imaging of central nervous system vasculitis].
AB  - Vasculitis involving the central nervous system presents with infarction and
      hemorrhage, which are often nonspecific findings. Laboratory examinations are
      essential for diagnosis of vasculitis in addition to comprehensive and systematic
      review of the clinical course. Although most findings tend to be nonspecific,
      enhancement and thickening of the vascular wall indicate vasculitis.
      Visualization of the vascular wall requires selection of the appropriate imaging
      modality and mode of image acquisition. Contrast-enhanced CT, MRI, and FDG-PET
      are useful for visualizing large vessel vasculitis, while CT, MRI, and
      angiography are effective for medium vessel vasculitis. The use of ultrasound is
      limited to evaluating vessels on the body surface. Although relatively thick
      vessels can be demonstrated by angiography, complete survey of small vessels is
      difficult. Here, we summarize the characteristics of each imaging modality and
      imaging findings of typical vasculitides-Takayasu arteritis, giant cell
      arteritis, ANCA-associated vasculitis, Behcet's disease, primary angiitis of the
      CNS, and vasculitis associated with systemic disease. Differential diagnoses are
      also shown, including infective endocarditis, tuberculous meningitis, Ehlers
      Danlos syndrome, and reversible cerebral vasoconstriction syndrome. 

PMID- 25846440
TI  - [Angiitis of the autonomic central nervous system].
AB  - Autonomic central nervous system (CNS) angiitis was classified with primary
      angiitis of the CNS (PACNS) or CNS angiitis secondary to systemic vasculitis.
      Mean onset age of PACNS was about 50 years. Typical symptoms were a chronic
      progressive headache and encephalopathy. Cerebrospinal fluid analysis was
      compatible with aseptic meningitis. Findings from imaging were varied and
      included arterial stenosis. Exclusion diagnosis of PACNS mimics and a brain
      biopsy were required for a definite diagnosis. Some collagen diseases could cause
      secondary CNS vasculitis. Patients with secondary CNS vasculitis were required
      more extensive immunosuppression therapy. 

PMID- 25846441
TI  - [Central nervous system Vasculitis due to infectious diseases].
AB  - Varicella zoster virus may cause vasculitis or vasculopathy, and positive
      polymerase chain reactions for varicella zoster virus deoxyribonucleic acid in
      the cerebrospinal fluid and/or the intrathecal synthesis of antibodies to the
      varicella zoster virus suggest these diagnoses. Meningovascular syphilis may
      involve the middle cerebral artery and basilar artery and may cause a stroke.
      Aspergillus is vasoinvasive and may cause hemorrhagic infarction by forming an
      intravascular thrombus. 

PMID- 25846442
TI  - [Inflammatory cerebral amyloid angiopathy].
AB  - Inflammatory cerebral amyloid angiopathy (CAA) typically affects older patients
      who present with acute or subacute cognitive decline, headache, behavioral
      change, seizures, and focal neurological deficits. Brain magnetic resonance
      imaging (MRI) reveals patchy or confluent asymmetric white matter
      hyperintensities on T2-weighted or fluid-attenuated inversion recovery images,
      which indicates vasogenic edema, and previous lobar hemorrhages and/or multiple
      lobar microbleeds on T2<sup>*</sup>-weighted gradient-recalled echo or
      susceptibility-weighted imaging. Neuropathological findings include frank
      vasculitis and/or perivascular inflammation with mononuclear or multinucleated
      giant cells that are associated with amyloid-beta (Abeta)-laden vessels.
      Importantly, these findings suggest that these patients may respond well to
      immunosuppressive treatment with high-dose corticosteroids and/or
      cyclophosphamide. The pathogenesis of this syndrome is still unknown, although
      anti-Abeta autoantibodies in the cerebrospinal fluid may mediate inflammatory
      processes against cerebrovascular Abeta. Moreover, MRI findings in patients with
      inflammatory CAA are very similar to those in patients with Alzheimer's disease
      who were treated with a monoclonal anti-Abeta antibody, and these findings are
      called amyloid-related imaging abnormalities (ARIA). Anti-Abeta autoantibodies in
      the cerebrospinal fluid might be a biomarker of future disease-modifying
      therapies for patients with Alzheimer's disease and CAA. 

PMID- 25846443
TI  - [Treatment for central nervous system vasculitis].
AB  - Central nervous system (CNS) vasculitis is classified into two categories based
      on whether it is primary or secondary. Primary CNS vasculitis is rare disorder of
      unknown cause that is restricted to the brain and spinal cord. Currently, there
      are no randomized clinical trials for treatment of primary CNS vasculitis.
      Therefore, treatment regimens for primary CNS vasculitis have been derived from
      therapeutic strategies used in other kinds of vasculitis. Early detection is
      important because corticosteroid treatment with or without cyclophosphamide can
      often prevent serious outcomes and may result in a favorable response. However,
      because some patients are intolerant or respond poorly to combination therapy,
      development of novel treatment options is eagerly awaited. Several
      immunosuppressive agents such as mycophenolate mofetil, tumor necrosis factor
      alpha blockers, and rituximab could be options for refractory patients. 

PMID- 25846444
TI  - [Mental time dysfunction in Parkinson's and Alzheimer's diseases].
AB  - Mental time is altered by a number of factors and the underlying neural
      processing involved is highly complicated. Recent research suggests that mental
      time in patients with particular neurological diseases is perceptually shorter
      than in normal individuals. This review introduces mental time dysfunction and a
      model for processing of mental time in Parkinson's and Alzheimer's disease.
      Although the two diseases show the same dysfunction of mental time in behavior,
      we expect the underlying neural mechanism to vary in each disease. It is possible
      that the dysfunction of mental time in Parkinson's disease is caused by the
      abnormal striatum acting as a pacemaker, while that in Alzheimer's disease is
      caused by abnormal hippocampal memory. 

PMID- 25846445
TI  - [Three neural networks that support syntactic processing in language].
AB  - Elucidation of language disorders is one of the fundamental issues in clinical
      neuroscience. We used magnetic resonance imaging and a syntactic task in Japanese
      to examine the behavior and brain structures of patients with a left frontal
      glioma. We successfully showed that they had different types of language
      disorders (particularly agrammatic comprehension) dependent on the location of
      the glioma. Moreover, we describe three neural networks that support syntactic
      processing, including an extensive network within the cerebellum and both
      hemispheres of the brain. 

PMID- 25846446
TI  - [A case with apraxia of tool use: selective inability to form a hand posture for
      a tool].
AB  - Impaired tool use is recognized as a symptom of ideational apraxia. While many
      studies have focused on difficulties in producing gestures as a whole, using
      tools involves several steps; these include forming hand postures appropriate for
      the use of certain tool, selecting objects or body parts to act on, and producing
      gestures. In previously reported cases, both producing and recognizing hand
      postures were impaired. Here we report the first case showing a selective
      impairment of forming hand postures appropriate for tools with preserved
      recognition of the required hand postures. A 24-year-old, right-handed man was
      admitted to hospital because of sensory impairment of the right side of the body,
      mild aphasia, and impaired tool use due to left parietal subcortical hemorrhage.
      His ability to make symbolic gestures, copy finger postures, and orient his hand
      to pass a slit was well preserved. Semantic knowledge for tools and hand postures
      was also intact. He could flawlessly select the correct hand postures in
      recognition tasks. He only demonstrated difficulties in forming a hand posture
      appropriate for a tool. Once he properly grasped a tool by trial and error, he
      could use it without hesitation. These observations suggest that each step of
      tool use should be thoroughly examined in patients with ideational apraxia.

PMID- 25846447
TI  - [A case of Wernicke's encephalopathy with detrusor-sphincter dyssynergia].
AB  - We report a case of a 54-year-old man with alcoholic Wernicke's encephalopathy.
      Neurological examination showed unconsciousness, absence of the oculocephalic
      reflex, generalized hyporeflexia, and urinary retention. The patient immediately
      regained consciousness after the administration of thiamine, but amnesia and
      cerebellar ataxia became apparent. The urinary retention persisted, and an
      urodynamic study showed detrusor-sphincter dyssynergia. Three months after the
      treatment, the urinary retention resolved, and a second urodynamic study showed
      disappearance of the detrusor-sphincter dyssynergia. Wernicke's encephalopathy
      involves the periaqueductal gray matter and the floor of the fourth ventricle.
      For the voiding reflex, the periaqueductal gray matter neurons project to the
      pontine micturition center, which seems to be located adjacent to the locus
      coeruleus. We concluded that lesions of the periaqueductal gray matter and/or the
      dorsolateral portion of the pons were responsible for the micturitional
      disturbance in the patient.

PMID- 25846448
TI  - [A case of representational dysgraphia and object representational disorder with
      unilateral spatial neglect].
AB  - We describe the case of a 48-year-old left-handed woman with unilateral neglect
      from a brain infarction in the area of the right basal ganglia and temporo
      parieto-occipital lobe. When a Kanji character was dictated to her, she wrote
      only the right side (tukuri) of the character. When copying a picture from the
      visual image of a left-right asymmetrical object, such as the side view of the
      dog, she drew the tail and a hind leg immediately but was unable to draw a
      picture of the dog from the left side. We asked her to imagine going around to
      the opposite side of the imaginary dog and to draw it from that perspective. She
      easily drew the left side first, resulting in a left-right inverted picture of
      what she had previously drawn. She then tried to slowly visualize the missing
      part of her imagery, and was able to draw only the right tip of the missing part.
      She could not compose a complete picture of the dog. These findings suggested
      that the impairment was in the imaging of the left side of a character or object
      and that this was a case of representational dysgraphia and object
      representational disorder with unilateral spatial neglect.

PMID- 25846449
TI  - A product of RpfB and RipA joint enzymatic action promotes the resuscitation of
      dormant mycobacteria.
AB  - Resuscitation-promoting factor proteins (Rpfs) are known to participate in
      reactivating the dormant forms of actinobacteria. Structural analysis of the Rpf
      catalytic domain demonstrates its similarity to lysozyme and to lytic
      transglycosylases - the groups of enzymes that cleave the beta-1,4-glycosidic
      bond between N-acetylmuramic acid (MurNAc) and GlcNAc, and concomitantly form a
      1,6-anhydro ring at the MurNAc residue. Analysis of the products formed from
      mycobacterial peptidoglycan hydrolysis reactions containing a mixture of RpfB and
      resuscitation-promoting factor interacting protein (RipA) allowed us to identify
      the suggested product of their action - N-acetylglucosaminyl-beta(1 -> 4)-N
      glycolyl-1,6-anhydromuramyl-L-alanyl-D-isoglutamate. To identify the role of this
      resulting product in resuscitation, we used a synthetic 1,6-anhydrodisaccharide
      dipeptide, and tested its ability to stimulate resuscitation by using the dormant
      Mycobacterium smegmatis model. It was found that the disaccharide-dipeptide was
      the minimal structure capable of resuscitating the dormant mycobacterial cells
      over the concentration range of 9-100 ng . mL(-1). The current study therefore
      provides the first insights into the molecular mechanism of resuscitation from
      dormancy involving a product of RpfB/RipA-mediated peptidoglycan cleavage.

PMID- 25846450
TI  - Is it time to target gut dysbiosis and immune dysfunction in the therapy of
      hepatic encephalopathy?
AB  - The development of overt hepatic encephalopathy (HE) in a patient with cirrhosis
      confers a damning prognosis with a 1-year mortality approaching 64%. This complex
      neuropsychiatric syndrome arises as a consequence of a dysfunctional gut-liver
      brain axis. HE has been largely neglected over the past 30 years, with the
      reliance on therapies aimed at lowering ammonia production or increasing
      metabolism following the seminal observation that the hepatic urea cycle is the
      major mammalian ammonia detoxification pathway and is key in the pathogenesis of
      HE. The relationship with ammonia is more clear-cut in acute liver failure; but
      in cirrhosis, it has become apparent that inflammation is a key driver and that a
      disrupted microbiome resulting in gut dysbiosis, bacterial overgrowth and
      translocation, systemic endotoxemia and immune dysfunction may be more important
      drivers. Therefore, it is important to re-focus our efforts into developing
      therapies that modulate the disrupted microbiome or alleviating its downstream
      consequences. 

PMID- 25846451
TI  - Modifications to the frailty phenotype criteria: Systematic review of the current
      literature and investigation of 262 frailty phenotypes in the Survey of Health,
      Ageing, and Retirement in Europe.
AB  - We conducted a systematic review to determine variability in how the criteria of
      the frailty phenotype (grip strength, weight loss, exhaustion, walking speed,
      physical activity) were assessed. We then evaluated the impact on estimating
      prevalence and mortality of modifying the criteria, using the Survey of Health,
      Ageing, & Retirement in Europe (SHARE). Five databases were searched for original
      research articles published after 2000, which evaluated frailty using the
      phenotypic criteria. Among the 264 included studies, 24 studies provided enough
      information to demonstrate that all criteria were assessed as proposed in the
      original frailty phenotype study by Fried et al. (2001). Physical inactivity and
      weight loss were the criteria most often modified. We then created 262 phenotypes
      from SHARE based on common modifications found in the review. Among these
      phenotypes, frailty prevalence ranged from 12.7% to 28.2%. Agreement with the
      primary frailty phenotype ranged from 0.662 to 0.967 and internal consistency
      ranged from 0.430 to 0.649. Women had 2.1-16.3% higher frailty prevalence than
      men. Areas under receiver operating characteristic curves for discriminating five
      year mortality ranged from 0.607 (95% CI: 0.583-0.630) to 0.668 (0.645-0.691).
      The frailty phenotype often has been modified, and these modifications have
      important impact on its classification and predictive ability.

PMID- 25846452
TI  - Dominant hand operating probe vs needle: a comparison study of ultrasound-guided
      needle placement in phantom models.
AB  - We conducted a replicated crossover design study to assess if using one's
      dominant hand for operating a probe vs directing a needle would affect the time
      taken, the number of needle passes and the accuracy of an ultrasound-guided
      procedure in phantom models. Twenty ultrasound-novice participants completed the
      task 10 times for each hand arrangement (alternating between attempts). The time
      taken and number of needle passes required for both dominant hand-probe and hand
      needle decreased over time (p = 0.001). Dominant hand-needle had a lower mean
      time used (p = 0.001) and fewer needle passes (p = 0.02) compared with hand
      probe. Sixty-five per cent of participants preferred using their dominant hand to
      direct the needle. When learning ultrasound-guided needle procedures on phantom
      models, use of the dominant hand to operate the needle is associated with a
      shorter procedure time and fewer needle passes.

PMID- 25846453
TI  - Presumptive congenital radial head sub-luxation in a shih tzu: successful
      management by radial head ostectomy.
AB  - Congenital radial head sub-luxation was diagnosed in a 7-month-old, neutered male
      shih tzu that presented with a limb deformity and severe lameness of the right
      fore limb. Radiography revealed a craniolateral sub-luxation of the right radial
      head, which was treated by radial head ostectomy, fixation of the radius to the
      ulna with a screw and joint stabilisation with suture-anchors and cerclage wire.
      Surgical treatment followed by physiotherapy resulted in a fully functional, well
      aligned and non-painful elbow. To the authors' knowledge this is the first case
      report of a congenital radial head sub-luxation in a craniolateral direction in a
      dog and also one successfully managed with radial head ostectomy and radioulnar
      synostosis. 

PMID- 25846454
TI  - Studies on the development of 169Yb-brachytherapy seeds: New generation
      brachytherapy sources for the management of cancer.
AB  - This paper describes development of (169)Yb-seeds by encapsulating 0.6-0.65 mm
      (phi) sized (169)Yb2O3 microspheres in titanium capsules. Microspheres
      synthesized by a sol-gel route were characterized by XRD, SEM/EDS and ICP-AES.
      Optimization of neutron irradiation was accomplished and (169)Yb-seeds up to 74
      MBq of (169)Yb could be produced from natural Yb2O3 microspheres, which have the
      potential for use in prostate brachytherapy. A protocol to prepare (169)Yb
      brachytherapy sources (2.96-3.7 TBq of (169)Yb) with the use of enriched targets
      was also formulated.

PMID- 25846455
TI  - Seabed radioactivity based on in situ measurements and Monte Carlo simulations.
AB  - Activity concentration measurements were carried out on the seabed, by
      implementing the underwater detection system KATERINA. The efficiency calibration
      was performed in the energy range 350-2600 keV, using in situ and laboratory
      measurements. The efficiency results were reproduced and extended in a broadened
      range of energies from 150 to 2600 keV, by Monte Carlo simulations, using the
      MCNP5 code. The concentrations of (40)K, (214)Bi and (208)Tl were determined
      utilizing the present approach. The results were validated by laboratory
      measurements.

PMID- 25846456
TI  - Profiling of actionable gene alterations in ovarian cancer by targeted deep
      sequencing.
AB  - To construct a profile of therapeutically actionable gene alterations in the
      major histological types of ovarian cancer, 72 Japanese patients with surgically
      resected ovarian cancers were selected from an original cohort consisting of 267
      patients who had not received pre-treatment before surgery. Somatic mutations and
      copy number alterations at 740 hotspots in 46 cancer-related genes were detected
      by deep sequencing of genomic DNAs obtained from snap-frozen tumor tissues using
      a next generation sequencer. The alterations were verified by Sanger sequencing
      and quantitative genomic PCR. Mutations and/or copy number aberrations which will
      make tumors respond to molecular targeting drugs were detected in nine genes of
      35/72 (48.6%) patients; PIK3CA (25.0%), KRAS (13.9%), ERBB2 (4.3%), PTEN (2.8%),
      RB1 (2.8%), CDKN2A (2.8%), AKT1 (1.4%), CTNNB1 (1.4%) and NRAS (1.4%). These
      mutations tended to occur in a mutually exclusive manner. Non-serous histological
      type tumors showed such actionable gene alterations frequently (32/47; 68.1%).
      Therefore, ovarian cancers, particularly of non-serous types, frequently carry
      gene aberrations that link to therapy using molecular targeting drugs.

PMID- 25846457
TI  - Exome sequencing identifies a homozygous C5orf42 variant in a Turkish kindred
      with oral-facial-digital syndrome type VI.
AB  - Oral-facial-digital syndrome type VI (OFDVI) is a rare ciliopathy in the spectrum
      of Joubert syndrome (JS) and distinguished from other oral-facial-digital
      syndromes by metacarpal abnormalities with central polydactyly and by a molar
      tooth sign on cranial MRI. Additional characteristic features include short
      stature, micrognathia, posteriorly rotated low-set ears, hypertelorism,
      epicanthal folds, broad nasal tip, tongue hamartoma, upper lip notch, intraoral
      frenula, cleft lip/palate, and renal anomalies. Recently, novel mutations in
      C5orf42 were identified in 9 out of 11 OFDVI families. In a subsequent study
      C5orf42 was found to be mutated in only 2 out of 17 OFDVI probands while 28
      patients with a pure JS phenotype also had pathogenic mutations of C5orf42. We
      report on two affected cousins diagnosed with OFDVI who were born from first
      degree cousin marriages. Whole exome sequencing (WES) identified a homozygous
      predicted damaging missense mutation (c.4034A > G; p.Gln1345Arg) in the C5orf42
      gene. Our data contribute to the evidence that C5orf42 is one of the causative
      genes for OFDVI.

PMID- 25846458
TI  - Acute pediatric encephalitis neuroimaging: single-institution series as part of
      the California encephalitis project.
AB  - PURPOSE: Diagnosing pediatric encephalitis is challenging because of varied
      clinical presentation, nonspecific neuroimaging features, and rare confirmation
      of causality. We reviewed acute neuroimaging of children with clinically
      suspected encephalitis to identify findings that may correlate with etiology and
      length of stay. METHODS: Imaging of 141 children with clinically suspected
      encephalitis as part of The California Encephalitis Project from 2005 to 2012 at
      a single institution was reviewed to compare the extent of neuroimaging
      abnormalities to patient age, gender, length of stay, and unknown, possible, or
      confirmed pathogen. Scan review was blinded and categorized by extent and
      distribution of abnormal findings. RESULTS: Abnormal findings were evident on 23%
      (22/94) of computed tomography and 50% (67/134) of magnetic resonance imaging
      studies in the acute setting. Twenty children with normal admission computed
      tomography had abnormal findings on magnetic resonance imaging performed within 2
      days. Length of stay was significantly longer among children with abnormal acute
      magnetic resonance imaging (P < 0.001) and correlated with increased complexity
      (Spearman rho = 0.4, P < 0.001) categorized as: no imaging abnormality, meningeal
      enhancement and/or focal nonenhancing lesion, multifocal lesions, confluent
      lesions, and lesions plus diffusion restriction, hemorrhage, or hydrocephalus.
      There was no correlation between neuroimaging findings and an identifiable
      pathogen (P = 0.8). CONCLUSION: Abnormal magnetic resonance imaging findings are
      more common than abnormal computed tomography findings in pediatric encephalitis.
      Increasing complexity of magnetic resonance imaging findings correlated with
      disease severity as evidenced by longer length of stay, but were not specific for
      an identifiable pathogen using a standardized diagnostic encephalitis panel.

PMID- 25846459
TI  - miR-29a modulates tumor necrosis factor-alpha-induced osteogenic inhibition by
      targeting Wnt antagonists.
AB  - We previously found that miR-29a was significantly downregulated in Ankylosing
      spondylitis (AS) patients, a chronic inflammatory disease associated with bone
      metabolic disorder, however, the underlying mechanism remains unclear. In this
      study, we demonstrated that miR-29a regulates tumor necrosis factor-alpha (TNF
      alpha) mediated bone loss mainly by targeting DKK1 and GSK3beta, thus activating
      the Wnt/beta-catenin pathway. Our findings may provide new insight into the
      pathogenesis of the bone metabolism disorder in inflammation environment and
      provide promising therapeutic target. 

PMID- 25846460
TI  - Protein adsorption, desorption, and aggregation mediated by solid-liquid
      interfaces.
AB  - Adsorption of proteins to solid-fluid interfaces is often empirically found to
      promote formation of soluble aggregates and larger, subvisible, and visible
      particles, but key stages in this process are often difficult to probe directly.
      Aggregation mediated by adsorption to water-silicon oxide (SiOx) interfaces, akin
      to hydrated glass surfaces, was characterized as a function of pH and ionic
      strength for alpha-chymotrypsinogen (aCgn) and for a monoclonal antibody (IgG1).
      A flow cell permitted neutron reflectivity for protein layers adsorbed to clean
      SiOx surfaces, as well as after successive "rinse" steps. Aggregates recovered in
      solution after gently "rinsing" the surface were characterized by neutron
      scattering, microscopy, and fluorescence spectroscopy. IgG1 molecules oriented
      primarily "flat" against the SiOx surface, with the primary protein layer
      desorbed to a minimal extent, whereas a diffuse overlayer was easily rinsed off.
      aCgn molecules were resistant to desorption when they appeared to be unfolded at
      the interface, but were otherwise easily removed. For cases where strong binding
      occurred, protein that did desorb was a mixture of monomer and small amounts of
      HMW aggregates (for aCgn) or subvisible particles (for IgG1). Changes in
      adsorption and/or unfolding with pH indicated that electrostatic interactions
      were important in all cases.

PMID- 25846461
TI  - [Wells Syndrome in children and atopy: Retrospective study of 11 cases and review
      of the literature].
AB  - BACKGROUND: Well's syndrome, or eosinophilic cellulitis, is rare in childhood,
      with fewer than 40 pediatric cases being reported since 1979. The physiopathology
      is unknown. PATIENTS AND METHODS: In February 2012, members of the research group
      of the Department of Pediatric Dermatology Society submitted their case of Wells'
      syndrome in children aged 0-15 years. Details of clinical, biological and
      histological features and of therapeutic strategies were collected by physicians
      using a standardized questionnaire. Pictures were reviewed by the authors.
      RESULTS: Eleven patients were included (average age: 6 years), with a strong
      prevalence of atopy (63%). Two types of clinical manifestation were noted: single
      or multiple cellulitis associated or not with vesiculobullous lesions and fixed
      urticaria. Eighty-two percent of patients had pruritus and 73% had eosinophilia.
      For all patients, histological examination of skin biopsies showed an
      eosinophilic infiltrate extending in the dermis with associated Sweet-like
      neutrophilic infiltrate being seen in 2 patients. The course of the disease was
      protracted (mean duration: 8 months) with flare-ups. Treatment varied depending
      on the doctors (topical or systemic steroids, tacrolimus and dapsone).
      DISCUSSION: Our study confirms some of the data in the literature concerning the
      clinical, histological features and course of Well's syndrome in children. The
      key information is the high prevalence of atopic children hitherto unreported. In
      a setting of insect bites, vaccination, infection or traumatism, this unusual
      background could explain the onset of inflammatory reaction with eosinophils.
      Oral or topical steroids appear to be the first-line treatment in children when
      necessary. CONCLUSION: Well's syndrome in children is rare and characterized by
      its polymorphism. We report for the first time in a series of patients a high
      prevalence of atopy, which raises new perspectives in understanding these rare
      diseases. We propose topical steroids as first-line therapy in children with
      superficial lesions, with oral steroids being given for cellulitic lesions or
      where topical therapy fails.

PMID- 25846462
TI  - [Item 197 - UE 7 Organ transplantation: skin complications].

PMID- 25846465
TI  - [Foreword].

PMID- 25846463
TI  - [Item 165 - UE 6 HIV infection: mucocutaneous manifestations of primary infection
      with HIV].

PMID- 25846464
TI  - [Item 183 - UE 7 Mucocutaneous hypersensitivity and allergies in children and
      adults].

PMID- 25846466
TI  - [Item 110 - UE 4 Autoimmune bullous dermatosis].

PMID- 25846467
TI  - [Acute finger ischemia: A retrospective study of 13 patients].
AB  - BACKGROUND: Acute ischemia of the upper limbs is rare in comparison with ischemia
      of the lower limbs. The origins of this condition are varied. GOALS: We
      retrospectively analyzed cases of acute finger ischemia (Raynaud's phenomena was
      excluded) in a dermatology department between 2008 and 2013 in order to evaluate
      the etiology and management of this phenomenon. RESULTS: Thirteen cases of finger
      ischemia were reported. The mean age was 54 years. Active smoking was noted in 11
      cases. Ischemia was acute in 9 cases and subacute in 4 cases. The location was
      unilateral in 10 cases and bilateral in 2. Etiologies were: dysplasia of the
      palmar arch, antiphospholipid antibody syndrome, frostbite, distal arteritis
      linked to smoking, paraneoplastic arteritis, Buerger's disease, polyarteritis
      nodosa, stenosis of the subclavian artery, and 3 cases of embolic origin (ulnar,
      cardiac, and paraneoplastic aneurysm). In the acute phase, antiplatelets were
      given in 6 cases, anticoagulants in 10 cases and ilomedin in 6 cases.
      Sympathectomy was performed in 1 case and amputation in 2 cases. DISCUSSION: This
      study illustrates the diversity of etiologies of finger ischemia. The etiological
      test battery should be broad and include immunological and thrombophilia tests,
      arterial and cardiac investigations, cervical radiography and CT scan (screening
      for cancer). Close collaboration between dermatologists, hematologists, vascular
      surgeons and radiologists is essential for the management of these patients.

PMID- 25846468
TI  - [Item 113 - UE 4 Pruritus].

PMID- 25846469
TI  - [Item 109 - UE 4 Facial dermatoses: acne, rosacea, seborrheic dermatitis].

PMID- 25846470
TI  - [Item 152 - UE 6 Mucocutaneous mycotic and and bacterial infections].

PMID- 25846471
TI  - [Item 112 - UE 4 Exanthema and erythroderma].

PMID- 25846472
TI  - [Item 111 - UE 4 Hemangiomas and skin vascular malformations].

PMID- 25846473
TI  - [Item 160 - UE 6 Febrile childhood exanthemas].

PMID- 25846475
TI  - Alpha fetoprotein mediates HBx induced carcinogenesis in the hepatocyte
      cytoplasm.
AB  - Although tumor-associated fetal protein AFP has demonstrated utility as a
      clinical tumor marker, the significance of intracellular AFP is still unclear.
      The aim of this study was to explore the role of cytoplasmic AFP during HBx
      induced carcinogenesis, which had not previously been recognized; 614 HCC
      patients were analyzed for correlation of HBV infection with AFP level, and much
      higher AFP levels were found in HBsAg positive patients. Tumor tissue specimens
      from 20 HCC patients were used for analysis of AFP and GADD45alpha. Analysis of
      HCC specimens showed that upregulation of cytoplasmic AFP is associated with down
      regulation of GADD45alpha in neoplastic tissue. Transfected HBx promotes
      transcription of AFP by acting on the elements in the AFP gene regulatory region.
      HBx itself did not directly impact transcription of GADD45alpha. However, the
      obstruction of RAR signaling by HBx induced elevation of AFP, which led to down
      regulation of GADD45alpha. Cytoplasmic AFP was able to interact with RAR,
      disrupting its entrance into the nucleus and binding to the elements in the
      regulatory region of the GADD45alpha gene. Knockdown of AFP in siRNA-transfected
      AFP positive cell lines was synchronously associated with an incremental increase
      of RAR binding to DNA, as well as upregulation of GADD45alpha and it was contrary
      in AFP gene-transfected AFP negative cell lines. These results indicate
      cytoplasmic AFP is not only a histochemical tumor biomarker for human hepatoma
      but is also an intracellular signal molecule and potential participant in HBx
      induced hepatocarcinogenesis. 

PMID- 25846474
TI  - [Item 190 - UE 7 Disseminated lupus erythematosus. Antiphospholipid syndrome].

PMID- 25846476
TI  - Should patients prescribed long-term low-dose aspirin receive proton pump
      inhibitors? A systematic review and meta-analysis.
AB  - BACKGROUND: Several clinical guidelines recommend the use of proton pump
      inhibitors (PPIs) in patients taking low-dose aspirin but report no or limited
      supporting data. We conducted a systematic review and meta-analysis to examine
      the effects of co-administration of PPIs in patients taking low-dose aspirin on
      the risks of adverse gastrointestinal (GI) and cardiovascular (CV) events, and on
      patient adherence to aspirin. METHODS: We searched PUBMED, EMBASE and Cochrane
      Central Register of Controlled Trials databases for relevant articles published
      through November 2013. We included randomised controlled trials (RCTs) and
      observational studies in patients taking low-dose aspirin with and without PPIs.
      Risk of bias was assessed using the Cochrane Collaboration's tool (for RCTs) and
      the Newcastle-Ottawa Scale (for observational studies). Pooled risk ratios (RRs)
      were computed using a random-effects model. RESULTS: We included 13 studies, of
      which 12 (2 RCTs and 10 observational studies) reported on GI events, and one
      (cohort study) on both GI bleeding and CV events. No study reported on adherence
      to aspirin. Co-administration of PPIs in patients receiving low-dose aspirin was
      associated with risk reductions of 73% (RR 0.27, 95% CI 0.17-0.42) and 50% (RR
      0.50, 95% CI 0.32-0.80) in the occurrence of peptic ulcer and GI bleeding
      respectively. There was evidence of bias in publications reporting on the GI
      events. CONCLUSIONS: The practice of co-prescribing PPIs in patients taking low
      dose aspirin is supported by some data, but the evidence is rather weak. It
      currently remains unclear whether the benefits of co-administration of PPIs in
      users of low-dose aspirin outweigh their potential harms.

PMID- 25846477
TI  - Selective Cyclization of Arylnitrones to Indolines under External Oxidant-Free
      Conditions: Dual Role of Rh(III) Catalyst in the C-H Activation and Oxygen Atom
      Transfer.
AB  - The first example of Rh(III)-catalyzed cyclization of arylnitrones to indolines
      under external oxidant-free conditions is presented. An intermolecular coupling
      of arylnitrones with internal alkynes is made possible by the dual role of the
      Cp*Rh(III) catalyst mediating both the C-H bond activation and O-atom transfer.
      Synthetically important and pharmacologically privileged indoline derivatives
      were obtained in good yields with high diastereoselectivity. 

PMID- 25846478
TI  - Plant community structure regulates responses of prairie soil respiration to
      decadal experimental warming.
AB  - Soil respiration is recognized to be influenced by temperature, moisture, and
      ecosystem production. However, little is known about how plant community
      structure regulates responses of soil respiration to climate change. Here, we
      used a 13-year field warming experiment to explore the mechanisms underlying
      plant community regulation on feedbacks of soil respiration to climate change in
      a tallgrass prairie in Oklahoma, USA. Infrared heaters were used to elevate
      temperature about 2  degrees C since November 1999. Annual clipping was used to
      mimic hay harvest. Our results showed that experimental warming significantly
      increased soil respiration approximately from 10% in the first 7 years (2000
      2006) to 30% in the next 6 years (2007-2012). The two-stage warming stimulation
      of soil respiration was closely related to warming-induced increases in ecosystem
      production over the years. Moreover, we found that across the 13 years, warming
      induced increases in soil respiration were positively affected by the proportion
      of aboveground net primary production (ANPP) contributed by C3 forbs. Functional
      composition of the plant community regulated warming-induced increases in soil
      respiration through the quantity and quality of organic matter inputs to soil and
      the amount of photosynthetic carbon (C) allocated belowground. Clipping, the
      interaction of clipping with warming, and warming-induced changes in soil
      temperature and moisture all had little effect on soil respiration over the years
      (all P > 0.05). Our results suggest that climate warming may drive an increase in
      soil respiration through altering composition of plant communities in grassland
      ecosystems. 

PMID- 25846479
TI  - Unintended allergens in precautionary labelled and unlabelled products pose
      significant risks to UK allergic consumers.
AB  - BACKGROUND: Allergens in food may pose a risk to allergic consumers. While there
      is EU regulation for allergens present as an ingredient, this is not the case for
      unintended allergen presence (UAP). Food companies use precautionary allergen
      labels to inform allergic individuals of a potential risk from UAPs. This study
      investigates the risk of an allergic reaction within the milk-, wheat-, hazelnut-
      and peanut-allergic populations when ingesting UK foods across multiple product
      categories with and without precautionary allergen labelling. METHODS: Allergen
      risk assessment using probabilistic techniques enables the estimation of the
      residual risk after the consumption of a product that unintentionally contains an
      allergen. RESULTS: Within this selection of UK products, the majority that tested
      positive for an allergen contained a concentration of allergen predicted to cause
      a reaction in >1% of the allergic population. The concentrations of allergens
      measured were greater than the VITAL((r)) 2.0 action levels and would trigger
      precautionary allergen labelling. This was found for products both with and
      without precautionary allergen labelling. CONCLUSIONS: The results highlight the
      need for the food industry and regulators to adopt a transparent, risk-based
      approach for the communication of the risk associated with potential cross
      contact that could occur in the processing facility or production chain.

PMID- 25846480
TI  - Hill-Sachs lesion location: does it play a role in engagement?
AB  - OBJECTIVE: To see if there is an association between engagement on physical
      examination (PE) and the location of the Hill-Sachs lesion (HSL) as assessed by
      the modified biceps angle. MATERIALS AND METHODS: Sixty-two patients with a
      history of anterior shoulder dislocation, who underwent preoperative MRI and
      arthroscopy at our institution and were tested for engagement on PE, were
      collected. Two musculoskeletal radiologists reviewed the MR studies, noting the
      presence of an HSL and documenting the location of the HSL with the modified
      biceps angle. Statistical analysis included the Mann-Whitney (MW) test and ROC
      (receiver-operating characteristic) curve. RESULTS: Of 62 patients, there were 58
      males and 4 females with a mean age of 30 (range 18-59 years). Twenty patients
      demonstrated engagement on PE, while 42 did not. All patients had evidence of an
      HSL on MRI and arthroscopy. The mean biceps angle for the engaging group was
      151.5 +/- 13.9 degrees , and 142.4 +/- 17.3 degrees  for the non-engaging group.
      The biceps angle was statistically significantly higher among patients who had
      engagement compared to those who did not (p = 0.027). Overall, diagnostic
      accuracy was highest for a biceps angle >149 degrees , which resulted in a
      sensitivity of 70% and specificity of 67%. CONCLUSION: The modified biceps angle,
      as measured on MRI, was significantly higher in patients who demonstrated
      engagement on physical examination than in those who did not. This supports the
      theory that the location of the Hill-Sachs lesion may play a role in engagement
      and may be its most important characteristic when determining its significance.

PMID- 25846481
TI  - Histone deacetylase 3 inhibition improves glycaemia and insulin secretion in
      obese diabetic rats.
AB  - Failure of pancreatic beta cells to compensate for insulin resistance is a
      prerequisite for the development of type 2 diabetes. Sustained elevated
      circulating levels of free fatty acids and glucose contribute to beta-cell
      failure. Selective inhibition of histone deacetylase (HDAC)-3 protects pancreatic
      beta cells against inflammatory and metabolic insults in vitro. In the present
      study, we tested the ability of a selective HDAC3 inhibitor, BRD3308, to reduce
      hyperglycaemia and increase insulin secretion in a rat model of type 2 diabetes.
      At diabetes onset, an ambulatory hyperglycaemic clamp was performed. HDAC3
      inhibition improved hyperglycaemia over the study period without affecting weight
      gain. At the end of the hyperglycaemic clamp, circulating insulin levels were
      significantly higher in BRD3308-treated rats. Pancreatic insulin staining and
      contents were also significantly higher. These findings highlight HDAC3 as a key
      therapeutic target for beta-cell protection in type 2 diabetes. 

PMID- 25846482
TI  - Acid mine drainage neutralization in a pilot sequencing batch reactor using
      limestone from a paper and pulp industry.
AB  - This study investigated the implications of using two grades of limestone from a
      paper and pulp industry for neutralization of acid mine drainage (AMD) in a pilot
      sequencing batch reactor (SBR). In this regard, two grades of calcium carbonate
      were used to neutralize AMD in a SBR with a hydraulic retention time (including
      settling) of 100 min and a sludge retention time of 360 min, by simultaneously
      monitoring the Fe(II) removal kinetics and overall assessment of the AMD after
      treatment. The Fe(II) kinetics removal and overall AMD treatment were observed to
      be highly dependent on the limestone grade used, with Fe(II) completely removed
      to levels lower than 50 mg/L in cycle 1 after 30 min using high quality or pure
      paper and pulp limestone. On the contrary, the other grade limestone, namely
      waste limestone, could only achieve a similar Fe(II) removal efficiency after
      four cycles. It was also noticed that suspended solids concentration plays a
      significant role in Fe(II) removal kinetics. In this regard, using pure limestone
      from the paper and pulp industry will have advantages compared with waste
      limestone for AMD neutralization. It has significant process impacts for the SBR
      configuration as it allows one cycle treatment resulting in a significant
      reduction of the feed stock, with subsequent generation of less sludge during AMD
      neutralization. However, the use of waste calcium carbonate from the paper and
      pulp industry as a feed stock during AMD neutralization can achieve significant
      cost savings as it is cheaper than the pure limestone and can achieve the same
      removal efficiency after four cycles.

PMID- 25846483
TI  - Inverse association between serum total bilirubin levels and diabetic peripheral
      neuropathy in patients with type 2 diabetes.
AB  - Several studies have suggested that bilirubin, a potent innate antioxidant, plays
      a protective role against cardiovascular and microvascular disease. This study
      investigated the association between serum concentrations of total bilirubin (TB)
      and the presence of diabetic peripheral neuropathy (DPN) in Korean diabetic
      patients. This cross-sectional study involved 1207 patients aged more than 30
      years with type 2 diabetes. DPN was assessed according to clinical symptoms and
      physical examinations using Michigan Neuropathy Screening Instrument examination
      score, 10-g monofilament sensation, and current perception threshold. The
      subjects were stratified into gender-specific tertiles based on TB values, and
      the relationship between the TB values and DPN was analyzed. Compared with
      patients within the lowest TB tertile, those with higher TB levels consisted of
      patients with shorter duration of diabetes, lower HbA1c, better renal function,
      and less autonomic neuropathy, retinopathy, and albuminuria. Serum TB levels were
      inversely associated with DPN. In multivariate analysis for the development of
      DPN after adjusting for potential confounding factors including retinopathy,
      albuminuria, and autonomic neuropathy, the TB levels were inversely associated
      with the presence of DPN, both as a continuous variable [odds ratio (OR) per log
      standard deviation (SD) 0.79; 95% confidence interval (CI) 0.65-0.97; P = 0.022]
      and when categorized in tertiles (the highest vs. the lowest tertile; OR 0.63;
      95% CI 0.40-0.99; P = 0.046). Low serum bilirubin levels are significantly
      associated with DPN, independently of classic risk factors and other
      microvascular complications. Further investigation is necessary to determine
      whether serum bilirubin has a prognostic significance on DPN.

PMID- 25846485
TI  - Practice may not always make perfect (outcomes).

PMID- 25846484
TI  - Nanocurcumin protects cardiomyoblasts H9c2 from hypoxia-induced hypertrophy and
      apoptosis by improving oxidative balance.
AB  - Hypoxia-induced cardiomyocyte hypertrophy is evident; however, the distinct
      molecular mechanism underlying the oxidative stress-mediated damages to
      cardiomyocytes remains unknown. Curcumin (diferuloylmethane) is known for anti
      hypertrophic effects, but low bioavailability makes it unsuitable to exploit its
      pharmacological properties. We assessed the efficacy of nanotized curcumin, i.e.
      nanocurcumin, in ameliorating hypoxia-induced hypertrophy and apoptosis in H9c2
      cardiomyoblasts and compared it to curcumin. H9c2 cardiomyoblasts were challenged
      with 0.5 % oxygen, for 24 h to assess hypoxia-induced oxidative damage,
      hypertrophy and consequent apoptosis. The molecular mechanism underlying the
      protective efficacy of nanocurcumin was evaluated in regulating Raf-1/Erk-1/2
      apoptosis by caspase-3/-7 pathway and oxidative stress. Nanocurcumin ameliorated
      hypoxia-induced hypertrophy and apoptosis in H9c2 cells significantly (p <=
      0.01), by downregulating atrial natriuretic factor expression, caspase-3/-7
      activation, oxidative stress and stabilizing hypoxia-inducible factor-1alpha (HIF
      1alpha) better than curcumin. Nanocurcumin provides insight into its use as a
      potential candidate in curing hypoxia-induced cardiac pathologies by restoring
      oxidative balance. 

PMID- 25846487
TI  - The tail of the epidemic and the challenge of tracing the very last Ebola case.

PMID- 25846488
TI  - Ebola response missions: to go or not to go? Cross-sectional study on the
      motivation of European public health experts, December 2014.
AB  - We surveyed European infectious disease epidemiologists and microbiologists about
      their decisions to apply for Ebola response missions. Of 368 respondents, 49
      (15%) had applied. Applicants did not differ from non-applicants in terms of age,
      sex or profession but had more training in field epidemiology and more
      international experience. Common concerns included lack of support from families
      and employers. Clearer terms of reference and support from employers could
      motivate application and support outbreak response in West Africa.

PMID- 25846486
TI  - Nerve growth factor promotes reorganization of the axonal microtubule array at
      sites of axon collateral branching.
AB  - The localized debundling of the axonal microtubule array and the entry of
      microtubules into axonal filopodia are two defining features of collateral
      branching. We report that nerve growth factor (NGF), a branch-inducing signal,
      increases the frequency of microtubule debundling along the axon shaft of chicken
      embryonic sensory neurons. Sites of debundling correlate strongly with the
      localized targeting of microtubules into filopodia. Platinum replica electron
      microscopy suggests physical interactions between debundled microtubules and
      axonal actin filaments. However, as evidenced by depolymerization of actin
      filaments and inhibition of myosin II, actomyosin force generation does not
      promote debundling. In contrast, loss of actin filaments or inhibition of myosin
      II activity promotes debundling, indicating that axonal actomyosin forces
      suppress debundling. MAP1B is a microtubule associated protein that represses
      axon branching. Following treatment with NGF, microtubules penetrating filopodia
      during the early stages of branching exhibited lower levels of associated MAP1B.
      NGF increased and decreased the levels of MAP1B phosphorylated at a GSK-3beta
      site (pMAP1B) along the axon shaft and within axonal filopodia, respectively. The
      levels of MAP1B and pMAP1B were not altered at sites of debundling, relative to
      the rest of the axon. Unlike the previously determined effects of NGF on the
      axonal actin cytoskeleton, the effects of NGF on microtubule debundling were not
      affected by inhibition of protein synthesis. Collectively, these data indicate
      that NGF promotes localized axonal microtubule debundling, that actomyosin forces
      antagonize microtubule debundling, and that NGF regulates pMAP1B in axonal
      filopodia during the early stages of collateral branch formation.

PMID- 25846489
TI  - Australian Hajj pilgrims' knowledge, attitude and perception about Ebola,
      November 2014 to February 2015.
AB  - Upon return from Hajj 2014, 150 Australian pilgrims were interviewed about their
      understanding of the Ebola epidemic. Most (89%, 134/150) knew of the epidemic
      before travelling and 60% (80/134) of those knew Ebola transmits through body
      fluids. Pilgrims who received pre-travel health advice were more conscious of
      Ebola (69% vs 31%, p = 0.01) and adhered better to hand hygiene after touching an
      ill person (68% vs 31%, p < 0.01). Mass media was the main information source
      (78%).

PMID- 25846490
TI  - Evaluation of a point-of-care blood test for identification of Ebola virus
      disease at Ebola holding units, Western Area, Sierra Leone, January to February
      2015.
AB  - Current Ebola virus disease (EVD) diagnosis relies on reverse transcription-PCR
      (RT-PCR) technology, requiring skilled laboratory personnel and technical
      infrastructure. Lack of laboratory diagnostic capacity has led to diagnostic
      delays in the current West African EVD outbreak of 2014 and 2015, compromising
      outbreak control. We evaluated the diagnostic accuracy of the EVD bedside rapid
      diagnostic antigen test (RDT) developed by the United Kingdom's Defence Science
      and Technology Laboratory, compared with Ebola virus RT-PCR, in an operational
      setting for EVD diagnosis of suspected cases admitted to Ebola holding units in
      the Western Area of Sierra Leone. From 22 January to 16 February 2015, 138
      participants were enrolled. EVD prevalence was 11.5%. All EVD cases were
      identified by a positive RDT with a test line score of 6 or more, giving a
      sensitivity of 100% (95% confidence interval (CI): 78.2-100). The corresponding
      specificity was high (96.6%, 95% CI: 91.3-99.1). The positive and negative
      predictive values for the population prevalence were 79.0% (95% CI: 54.4-93.8)
      and 100% (95% CI: 96.7-100), respectively. These results, if confirmed in a
      larger study, suggest that this RDT could be used as a 'rule-out' screening test
      for EVD to improve rapid case identification and resource allocation.

PMID- 25846491
TI  - Wild bird surveillance around outbreaks of highly pathogenic avian influenza
      A(H5N8) virus in the Netherlands, 2014, within the context of global flyways.
AB  - Highly pathogenic avian influenza (HPAI) A(H5N8) viruses that emerged in poultry
      in east Asia since 2010 spread to Europe and North America by late 2014. Despite
      detections in migrating birds, the role of free-living wild birds in the global
      dispersal of H5N8 virus is unclear. Here, wild bird sampling activities in
      response to the H5N8 virus outbreaks in poultry in the Netherlands are summarised
      along with a review on ring recoveries. HPAI H5N8 virus was detected exclusively
      in two samples from ducks of the Eurasian wigeon species, among 4,018 birds
      sampled within a three months period from mid-November 2014. The H5N8 viruses
      isolated from wild birds in the Netherlands were genetically closely related to
      and had the same gene constellation as H5N8 viruses detected elsewhere in Europe,
      in Asia and in North America, suggesting a common origin. Ring recoveries of
      migratory duck species from which H5N8 viruses have been isolated overall provide
      evidence for indirect migratory connections between East Asia and Western Europe
      and between East Asia and North America. This study is useful for better
      understanding the role of wild birds in the global epidemiology of H5N8 viruses.
      The need for sampling large numbers of wild birds for the detection of H5N8 virus
      and H5N8-virus-specific antibodies in a variety of species globally is
      highlighted, with specific emphasis in north-eastern Europe, Russia and northern
      China.

PMID- 25846492
TI  - Laboratory support during and after the Ebola virus endgame: towards a sustained
      laboratory infrastructure.
AB  - The Ebola virus epidemic in West Africa is on the brink of entering a second
      phase in which the (inter)national efforts to slow down virus transmission will
      be engaged to end the epidemic. The response community must consider the
      longevity of their current laboratory support, as it is essential that diagnostic
      capacity in the affected countries be supported beyond the end of the epidemic.
      The emergency laboratory response should be used to support building structural
      diagnostic and outbreak surveillance capacity.

PMID- 25846493
TI  - Surveillance and Outbreak Response Management System (SORMAS) to support the
      control of the Ebola virus disease outbreak in West Africa.
AB  - In the context of controlling the current outbreak of Ebola virus disease (EVD),
      the World Health Organization claimed that 'critical determinant of epidemic size
      appears to be the speed of implementation of rigorous control measures', i.e.
      immediate follow-up of contact persons during 21 days after exposure, isolation
      and treatment of cases, decontamination, and safe burials. We developed the
      Surveillance and Outbreak Response Management System (SORMAS) to improve
      efficiency and timeliness of these measures. We used the Design Thinking
      methodology to systematically analyse experiences from field workers and the
      Ebola Emergency Operations Centre (EOC) after successful control of the EVD
      outbreak in Nigeria. We developed a process model with seven personas
      representing the procedures of EVD outbreak control. The SORMAS system
      architecture combines latest In-Memory Database (IMDB) technology via SAP HANA
      (in-memory, relational database management system), enabling interactive data
      analyses, and established SAP cloud tools, such as SAP Afaria (a mobile device
      management software). The user interface consists of specific front-ends for
      smartphones and tablet devices, which are independent from physical
      configurations. SORMAS allows real-time, bidirectional information exchange
      between field workers and the EOC, ensures supervision of contact follow-up,
      automated status reports, and GPS tracking. SORMAS may become a platform for
      outbreak management and improved routine surveillance of any infectious disease.
      Furthermore, the SORMAS process model may serve as framework for EVD outbreak
      modeling.

PMID- 25846494
TI  - Identification of common features of vehicle motion under drowsy/distracted
      driving: A case study in Wuhan, China.
AB  - Drowsy/distracted driving has become one of the leading causes of traffic crash.
      Only certain particular drowsy/distracted driving behaviors have been studied by
      previous studies, which are mainly based on dedicated sensor devices such as bio
      and visual sensors. The objective of this study is to extract the common features
      for identifying drowsy/distracted driving through a set of common vehicle motion
      parameters. An intelligent vehicle was used to collect vehicle motion parameters.
      Fifty licensed drivers (37 males and 13 females, M=32.5 years, SD=6.2) were
      recruited to carry out road experiments in Wuhan, China and collecting vehicle
      motion data under four driving scenarios including talking, watching roadside,
      drinking and under the influence of drowsiness. For the first scenario, the
      drivers were exposed to a set of questions and asked to repeat a few sentences
      that had been proved valid in inducing driving distraction. Watching roadside,
      drinking and driving under drowsiness were assessed by an observer and self
      reporting from the drivers. The common features of vehicle motions under four
      types of drowsy/distracted driving were analyzed using descriptive statistics and
      then Wilcoxon rank sum test. The results indicated that there was a significant
      difference of lateral acceleration rates and yaw rate acceleration between
      "normal driving" and drowsy/distracted driving. Study results also shown that,
      under drowsy/distracted driving, the lateral acceleration rates and yaw rate
      acceleration were significantly larger from the normal driving. The lateral
      acceleration rates were shown to suddenly increase or decrease by more than
      2.0m/s(3) and the yaw rate acceleration by more than 2.5 degrees /s(2). The
      standard deviation of acceleration rate (SDA) and standard deviation of yaw rate
      acceleration (SDY) were identified to as the common features of vehicle motion
      for distinguishing the drowsy/distracted driving from the normal driving. In
      order to identify a time window for effectively extracting the two common
      features, a double-window method was used and the optimized "Parent Window" and
      "Child Window" were found to be 55s and 6s, respectively. The study results can
      be used to develop a driving assistant system, which can warn drivers when any
      one of the four types of drowsy/distracted driving is detected. 

PMID- 25846495
TI  - Quantum confinement-tunable intersystem crossing and the triplet state lifetime
      of cationic porphyrin-CdTe quantum dot nano-assemblies.
AB  - Here, we report a ground-state interaction between the positively charged
      cationic porphyrin and the negatively charged carboxylate groups of the thiol
      ligands on the surface of CdTe quantum dots (QDs), leading to the formation of a
      stable nanoassembly between the two components. Our time-resolved data clearly
      demonstrate that we can dramatically tune the intersystem crossing (ISC) and the
      triplet state lifetime of porphyrin by changing the size of the QDs in the
      nanoassembly. 

PMID- 25846496
TI  - Clinical and pathological correlations of marrow PUMA and P53 expressions in
      myelodysplastic syndromes.
AB  - p53 is a key regulator of apoptosis. p53 upregulated modulator of apoptosis
      (PUMA) is a critical mediator of p53-dependent and independent apoptosis. The
      objective of this study was to evaluate the relationship of p53 and PUMA to the
      prognosis of MDS. Bone marrow biopsies of MDS patients at the time of diagnosis
      (n = 76) and at the time of transformation (n = 19) were included in the study
      group. The expression of p53 and PUMA was evaluated using immunohistochemistry.
      When compared to the control group, both p53 (p < 0.001) and PUMA (p = 0.012)
      expression levels were significantly higher in MDS group. In MDS group, there was
      a moderate positive correlation between p53 and PUMA expressions. PUMA expression
      was not correlated with event free and overall survival. However, overall
      survival was significantly lower in cases with p53 expression in more than 50% of
      the cells. There was an increase in PUMA expression in cases that showed
      transformation as compared to the initial diagnostic bone marrows but was not
      statistically significant. The correlation that existed between p53 and PUMA was
      lost in transformed cases. Our results showed that PUMA and p53 expressions are
      increased in MDS marrows compared to normal marrows. PUMA expression increases
      further during transformation while the expression of p53 is not significantly
      altered which suggests that PUMA alterations might be a late event during the
      evolution of MDS.

PMID- 25846497
TI  - Noncanonical Wnt5a-Ca(2+) -NFAT signaling axis in pesticide induced bone marrow
      aplasia mouse model: A study to explore the novel mechanism of pesticide
      toxicity.
AB  - According to case-control studies, long-term pesticide exposure can cause bone
      marrow aplasia like hematopoietic degenerative disease leading to impaired
      hematopoiesis and increased risk of aplastic anemia in human subjects. However,
      the exact mechanism of pesticide mediated hematotoxicity still remains elusive.
      In this study, we investigated the role of noncanonical Wnt signaling pathway, a
      crucial regulator of adult hematopoiesis, in pesticide induced bone marrow
      aplasia mouse model. Aplasia mouse model was developed following inhalation and
      dermal exposure of 5% aqueous mixture of common agriculturally used pesticides
      for 6 h/day for 5 days a week up to 90 days. After that, blood hemogram, marrow
      smear, cellularity, scanning electron microscopy, extramedullary hematopoiesis
      and flowcytometric expression analysis of noncanonical Wnt signaling components,
      such as Wnt 5a, fzd5, NFAT, IFN-gamma, intracellular Ca(2+) level were evaluated
      in the bone marrow hematopoietic stem/progenitor compartment of the control and
      pesticide induced aplasia groups of animals. Results showed that pesticide
      exposed mice were anemic with peripheral blood pancytopenia, hypocellular
      degenerative marrow, and extramedullary hematopoiesis in the spleen. Upon
      pesticide exposure, Wnt 5a expression was severely downregulated with a decline
      in intracellular Ca(2+) level. Moreover, downstream of Wnt5a, we observed sharp
      downregulation of NFATc2 transcription factor expression, the major target of
      pesticide toxicity and its target molecule IFN-gamma. Taken together, our result
      suggests that deregulation of Wnt5a-Ca(2+) -NFAT signaling axis in the
      hematopoietic stem/progenitor compartment plays a crucial role behind the
      pathogenesis of pesticide mediated bone marrow aplasia by limiting primitive
      hematopoietic stem cells' ability to maintain hematopoietic homeostasis and
      reconstitution mechanism in vivo during xenobiotic stress leading to ineffective
      hematopoiesis and evolution of bone marrow aplasia. (c) 2015 Wiley Periodicals,
      Inc. Environ Toxicol 31: 1163-1175, 2016. 

PMID- 25846498
TI  - Role of hepatocyte S6K1 in palmitic acid-induced endoplasmic reticulum stress,
      lipotoxicity, insulin resistance and in oleic acid-induced protection.
AB  - The excess of saturated free fatty acids, such as palmitic acid, that induces
      lipotoxicity in hepatocytes, has been implicated in the development of non
      alcoholic fatty liver disease also associated with insulin resistance. By
      contrast, oleic acid, a monounsaturated fatty acid, attenuates the effects of
      palmitic acid. We evaluated whether palmitic acid is directly associated with
      both insulin resistance and lipoapoptosis in mouse and human hepatocytes and the
      impact of oleic acid in the molecular mechanisms that mediate both processes. In
      human and mouse hepatocytes palmitic acid at a lipotoxic concentration triggered
      early activation of endoplasmic reticulum (ER) stress-related kinases, induced
      the apoptotic transcription factor CHOP, activated caspase 3 and increased the
      percentage of apoptotic cells. These effects concurred with decreased IR/IRS1/Akt
      insulin pathway. Oleic acid suppressed the toxic effects of palmitic acid on ER
      stress activation, lipoapoptosis and insulin resistance. Besides, oleic acid
      suppressed palmitic acid-induced activation of S6K1. This protection was mimicked
      by pharmacological or genetic inhibition of S6K1 in hepatocytes. In conclusion,
      this is the first study highlighting the activation of S6K1 by palmitic acid as a
      common and novel mechanism by which its inhibition by oleic acid prevents ER
      stress, lipoapoptosis and insulin resistance in hepatocytes. 

PMID- 25846499
TI  - In vivo systemic chlorogenic acid therapy under diabetic conditions: Wound
      healing effects and cytotoxicity/genotoxicity profile.
AB  - Oxidative stress occurs following the impairment of pro-oxidant/antioxidant
      balance in chronic wounds and leads to harmful delays in healing progress. A fine
      balance between oxidative stress and endogenous antioxidant defense system may be
      beneficial for wound healing under redox control. This study tested the
      hypothesis that oxidative stress in wound area can be controlled with systemic
      antioxidant therapy and therefore wound healing can be accelerated. We used
      chlorogenic acid (CGA), a dietary antioxidant, in experimental diabetic wounds
      that are characterized by delayed healing. Additionally, we aimed to understand
      possible side effects of CGA on pivotal organs and bone marrow during therapy.
      Wounds were created on backs of streptozotocin-induced diabetic rats. CGA (50
      mg/kg/day) was injected intraperitoneally. Animals were sacrificed on different
      days. Biochemical and histopathological examinations were performed. Side effects
      of chronic antioxidant treatment were tested. CGA accelerated wound healing,
      enhanced hydroxyproline content, decreased malondialdehyde/nitric oxide levels,
      elevated reduced-glutathione, and did not affect superoxide dismutase/catalase
      levels in wound bed. While CGA induced side effects such as cyto/genotoxicity, 15
      days of treatment attenuated blood glucose levels. CGA decreased lipid
      peroxidation levels of main organs. This study provides a better understanding
      for antioxidant intake on diabetic wound repair and possible pro-oxidative
      effects. 

PMID- 25846500
TI  - Cytotoxicity, cell uptake and microscopic analysis of titanium dioxide and silver
      nanoparticles in vitro.
AB  - Commercially manufactured nanomaterials are used massively for modification of
      products of everyday use, including products intended for children. Therefore
      their potential risks have to be ultimately studied. Aside from toxicity of
      nanomaterials with known specific parameters, the end-consumer is potentially
      endangered by materials with unknown specification. Commercially available
      products are not usually accompanied by parameter/specification sheet providing
      the consumer with sufficient chemico-physical parameters allowing the evaluation
      of possible toxic effects. The aim of this work was to evaluate the declared
      parameters of commercially available TiO2 and Ag NPs employing chemico-physical
      methods and consequently in vitro cytotoxicity and genotoxicity tests performed
      on non-cancer cell lines. Based on the results of our complex study we can
      conclude that the data provided by the producers are not in good agreement with
      the performed measurements. Furthermore, all tested NPs penetrated into the SVK14
      cells and all NPs had significant effect on the kinetics of ROS production in all
      cell lines (note: the ROS production has not been established as the major
      mechanism of cell damage elicited by Ag NPs). The study revealed greater
      cytotoxic potential of Ag NPs in comparison with TiO2 NPs and all of the studied
      NPs caused significant DNA damage. 

PMID- 25846501
TI  - Human systemic exposure to [14C]-paraphenylenediamine-containing oxidative hair
      dyes: Absorption, kinetics, metabolism, excretion and safety assessment.
AB  - Systemic exposure was measured in humans after hair dyeing with oxidative hair
      dyes containing 2.0% (A) or 1.0% (B) [(14)C]-p-phenylenediamine (PPD). Hair was
      dyed, rinsed, dried, clipped and shaved; blood and urine samples were collected
      for 48 hours after application. [(14)C] was measured in all materials, rinsing
      water, hair, plasma, urine and skin strips. Plasma and urine were also analysed
      by HLPC/MS/MS for PPD and its metabolites (B). Total mean recovery of
      radioactivity was 94.30% (A) or 96.21% (B). Mean plasma Cmax values were 132.6 or
      97.4 ng [(14)C]-PPDeq/mL, mean AUC(0-infinity) values 1415 or 966 ng [(14)C]
      PPDeq/mL*hr in studies A or B, respectively. Urinary excretion of [(14)C] mainly
      occurred within 24 hrs after hair colouring with a total excretion of 0.72 or
      0.88% of applied radioactivity in studies A or B, respectively. Only N,N'
      diacetylated-PPD was detected in plasma and the urine. A TK-based human safety
      assessment estimated margins of safety of 23.3- or 65-fold relative to respective
      plasma AUC or Cmax values in rats at the NOAEL of a toxicity study. Overall, hair
      dyes containing PPD are unlikely to pose a health risk since they are used
      intermittently and systemic exposure is limited to the detoxified metabolite N,N'
      diacetyl-PPD.

PMID- 25846502
TI  - Cancer-promoting effect of capsaicin on DMBA/TPA-induced skin tumorigenesis by
      modulating inflammation, Erk and p38 in mice.
AB  - Epidemiologic and animal studies revealed that capsaicin (8-methyl-N-vanillyl-6
      noneamide) can act as a carcinogen or cocarcinogen. However, the influence of
      consumption of capsaicin-containing foods or vegetables on skin cancer patients
      remains largely unknown. In the present study, we demonstrated that capsaicin has
      a cocarcinogenic effect on 9, 10-dimethylbenz[a]anthracene (DMBA)/12-O
      tetradecanoylphorbol-13-acetate (TPA)-induced skin tumorigenesis. Our results
      showed that topical application of capsaicin on the dorsal skin of DMBA-initiated
      and TPA-promoted mice could significantly accelerate tumor formation and growth
      and induce more and larger skin tumors than the model group (DMBA + TPA).
      Moreover, capsaicin could promote TPA-induced skin hyperplasia and tumor
      proliferation. Mechanistic study found that inflammation-related factors
      cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were highly
      elevated by pretreatment with capsaicin, suggesting an inflammation-dependent
      mechanism. Furthermore, mice that were administered capsaicin exhibited
      significant up-regulation of phosphorylation of nuclear factor kappaB (NF
      kappaB), Erk and p38 but had no effect on JNK. Thus, our results indicated that
      inflammation, Erk and P38 collectively played a crucial role in cancer-promoting
      effect of capsaicin on carcinogen-induced skin cancer in mice.

PMID- 25846503
TI  - Modulating effect of synthetic statins against damage induced by doxorubicin in
      somatic cells of Drosophila melanogaster.
AB  - The competitive inhibitors of HMG-CoA reductase, popularly known as statins,
      exert pleiotropic effects, which result from the ability of statins to inhibit
      the synthesis of isoprenoids, which are fundamental for the functioning of
      proteins responsible for intracellular signaling. Some recent studies suggest an
      important role associated with the use of antineoplastic atorvastatin and
      rosuvastatin, the statins most widely used today. In this study, the Drosophila
      wing spot test was used to evaluate possible protective effects of atorvastatin
      and rosuvastatin against damage induced by DXR. Larvae were chronically treated
      with negative control (ethanol 5%), positive control (DXR 0.125 mg/mL) and five
      different concentrations of atorvastatin and rosuvastatin. The results
      demonstrated absence of a mutagenic effect for the two statins tested. The
      analysis of the descendants co-treated with DXR and atorvastatin/rosuvastatin
      revealed a modulatory effect of these statins on damage induced by DXR. This
      effect was verified in all concentrations tested in the descendants of the ST and
      HB crosses treated with rosuvastatin, and only in descendants of the HB cross
      treated with atorvastatin. Induction of apoptosis and antioxidant activity appear
      to be the main mechanisms involved in reducing the frequency of mutant spots and
      consequent modulation of the damage induced by DXR.

PMID- 25846504
TI  - The Structural Stability of Graphene Anticorrosion Coating Materials is
      Compromised at Low Potentials.
AB  - Corrosion of engineered structures is a major problem causing an estimated
      economic loss of more than 2 trillion US dollars annually worldwide. Graphene has
      recently emerged as highly promising, low-cost, and transparent anticorrosion
      coating material. Herein, it is shown that a multilayer graphene film grown on Ni
      by chemical vapor deposition undergoes abrupt stability failure under galvanic
      corrosion conditions. The multilayer graphene coating was examined by optical
      microscopy, SEM, energy dispersive X-ray spectroscopy, Raman spectroscopy, and
      cyclic voltammetry after exposure to potentials between 600 and 1300 mV in
      alkaline solution. A fast and simple electrochemical method is proposed to
      sensitively quantify the damage caused by the applied potential bias. It is based
      on quantification of the oxidation signals generated by the underlying Ni-metal
      catalyst that is exposed by damage to the graphene film. It is shown that film
      damage can start at potentials as low as 900 mV and that macroscopic and
      extensive damage can be caused at potentials above 1000 mV. In addition, once the
      graphene film has been damaged, the corrosion rate of the underlying metal is
      significantly increased. These findings are of great importance for potential
      applications of multilayer graphene films in coating metal structures with huge
      industrial and economic implications. 

PMID- 25846505
TI  - A library of synthetic transcription activator-like effector-activated promoters
      for coordinated orthogonal gene expression in plants.
AB  - A library of synthetic promoters containing the binding site of a single designer
      transcription activator-like effector (dTALE) was constructed. The promoters
      contain a constant sequence, consisting of an 18-base long dTALE-binding site and
      a TATA box, flanked by degenerate sequences of 49 bases downstream and 19 bases
      upstream. Forty-three of these promoters were sequenced and tested in transient
      assays in Nicotiana benthamiana using a GUS reporter gene. The strength of
      expression of the promoters ranged from around 5% to almost 100% of the viral 35S
      promoter activity. We then demonstrated the utility of these promoters for
      metabolic engineering by transiently expressing three genes for the production of
      a plant diterpenoid in N. benthamiana. The simplicity of the promoter structure
      shows great promise for the development of genetic circuits, with wide potential
      applications in plant synthetic biology and metabolic engineering. 

PMID- 25846511
TI  - Quantification of turbulence and velocity in stenotic flow using spiral three
      dimensional phase-contrast MRI.
AB  - PURPOSE: Evaluate spiral three-dimensional (3D) phase contrast MRI for the
      assessment of turbulence and velocity in stenotic flow. METHODS: A-stack-of
      spirals 3D phase contrast MRI sequence was evaluated in vitro against a
      conventional Cartesian sequence. Measurements were made in a flow phantom with a
      75% stenosis. Both spiral and Cartesian imaging were performed using different
      scan orientations and flow rates. Volume flow rate, maximum velocity and
      turbulent kinetic energy (TKE) were computed for both methods. Moreover, the
      estimated TKE was compared with computational fluid dynamics (CFD) data. RESULTS:
      There was good agreement between the turbulent kinetic energy from the spiral,
      Cartesian and CFD data. Flow rate and maximum velocity from the spiral data
      agreed well with Cartesian data. As expected, the short echo time of the spiral
      sequence resulted in less prominent displacement artifacts compared with the
      Cartesian sequence. However, both spiral and Cartesian flow rate estimates were
      sensitive to displacement when the flow was oblique to the encoding directions.
      CONCLUSION: Spiral 3D phase contrast MRI appears favorable for the assessment of
      stenotic flow. The spiral sequence was more than three times faster and less
      sensitive to displacement artifacts when compared with a conventional Cartesian
      sequence.

PMID- 25846513
TI  - Recommendations for reporting histopathology studies: a proposal.

PMID- 25846514
TI  - van Leeuwenhoek microscopes-where are they now?
AB  - When Antonie van Leeuwenhoek died, he left over 500 simple microscopes,
      aalkijkers (an adaption of his microscope to allow the examination of blood
      circulation in the tails of small eels) and lenses, yet now there are only 10
      microscopes with a claim to being authentic, one possible aalkijker and six
      lenses. He made microscopes with more than one lens, and possibly three forms of
      the aalkijker. This paper attempts to establish exactly what he left and trace
      the fate of some of the others using the earliest possible documents and
      publications. 

PMID- 25846512
TI  - Activation of platelet protease-activated receptor-1 induces epithelial
      mesenchymal transition and chemotaxis of colon cancer cell line SW620.
AB  - The aim of the present study was to examine the role of protease-activated
      receptor-1 (PAR1)-stimulated platelet activation in the epithelial-mesenchymal
      transition (EMT) and migration of colon cancer cells, and to identify the
      underlying mechanisms. TFLLR-NH2, a PAR1 agonist, was used to activate platelets
      and the platelet supernatants were used to treat the SW620 colon cancer cell
      line. Expression of E-cadherin and vimentin on SW620 cells was detected by
      immunofluorescence and western blotting, and the level of the transforming growth
      factor beta1 (TGF-beta1) was measured using ELISA following the activation of
      platelets by TFLLR-NH2. miR-200b expression was detected using quantitative PCR
      in SW620 cells. In order to investigate the chemotactic ability of the SW620
      cells, the expression of CXC chemokine receptor type 4 (CXCR4) was measured by
      flow cytometry. Transwell migration assays were performed following exposure of
      the cells to the supernatant of PAR1-activated platelets. SW620 cells cultured in
      the supernatant of TFLLR-NH2-activated platelets upregulated E-cadherin
      expression and downregulated the vimentin expression. In the in vitro platelet
      culture system, a TFLLR-NH2 dose-dependent increase of secreted TGF-beta1 was
      detected in the supernatant. The activation of PAR1 on the platelets led to the
      inhibition of miR-200b expression in the SW620 cells that were cultured in
      platelet-conditioned media. The number of SW620 cells that penetrated through the
      Transwell membrane increased with the dose of TFLLR-NH2 used to treat the
      platelets. The percentage of CXCR4-positive SW620 cells was significantly higher
      when they were exposed to the supernatant of platelets cultured for 24 h with
      PAR1 agonist than when cultured in non-conditioned media (40.89 +/- 6.74 vs. 3.47
      +/- 1.40%, P < 0.01). Platelet activation with a PAR1 agonist triggered TGF-beta
      secretion, which induced EMT of SW620 human colon cancer cells via the
      downregulation of miR-200b expression, and activated platelets had a chemotactic
      effect on colon cancer cells mediated by the upregulation of CXCR4 on the cell
      surface.

PMID- 25846515
TI  - Insight into proteomic investigations of Neisseria meningitidis serogroup C
      strain L91543 from analysis of its genome sequence.
AB  - Here, we describe the draft sequence of a virulent isolate of Neisseria
      meningitidis strain L91543, belonging to serogroup C. The findings from previous
      proteomic and metabolomic studies of this strain can now be further interpreted
      with genomic analysis. Comparative analysis of the genome sequence revealed close
      similarity and localized synteny with the genome sequence of N. meningitidis
      serogroup C strain, FAM18. Polymorphisms were identified in the signal peptide
      sequence of factor H binding protein, a target for new meningococcal vaccines,
      which may result in its inefficient translocation across the cytoplasmic membrane
      affecting its processing (lipidation and cleavage of the signal peptide) and
      transportation to the outer membrane in strain L91543. This would explain the
      unusual proteomic data for factor H binding protein for this strain. NadA,
      another target for new vaccines, and the MtrR regulator, which controls
      expression of NadA, both contain SNPs between strains L91543 and FAM18. The
      genome sequence data were generated using Ion Torrent PGM sequencing, assembled
      into 50 contigs with 64* coverage and annotated with 2262 genes, 14 rRNAs and 56
      tRNAs. The availability of the genome of N. meningitidis strain L91543 will aid
      our understanding of the proteome of this organism, importantly its vaccine
      antigens. 

PMID- 25846516
TI  - Historical microbiology, is it relevant in the 21st century?
AB  - Facsimile microscopes have been used to examine the possibilities of van
      Leeuwenhoek microscopes with a range of magnifications, particularly to confirm
      that bacteria can be seen if the microscope is strong enough. The relevance of
      historical microbiology in education is also illustrated by adapting versions of
      van Leeuwenhoek's pepper water experiment and Beijerinck's use of bioluminescent
      bacteria as oxygen probes. These experiments can demonstrate fundamentals such as
      enrichment and isolation cultures, physiology and experimental planning as well
      as critical reading of published material. 

PMID- 25846517
TI  - Purging using the Heimlich maneuver among children and adolescents with eating
      disorders.
AB  - This case report describes five independent cases of children and adolescents
      assessed for eating disorders who disclosed using the Heimlich maneuver as a
      purging technique. The maneuver is meant to be used only in life or death
      situations, likely once or less in any person's lifetime. A child or adolescent
      with an eating disorder may be using it to self-induce vomiting on a daily basis,
      increasing the risk of complications, including potential damage to major organs
      of the body. Asking patients who purge to elaborate on the methods with which
      they purge can provide clinicians with fuller information, improving their
      ability to select appropriate medical tests and interventions. Thorough
      investigations of physical complaints during the patient assessment may be
      warranted, including examining patients for possible rib fractures, hemorrhages,
      perforations of the hollow viscous, and other forms of blunt abdominal traumas.

PMID- 25846518
TI  - Physical Stimuli-Induced Chondrogenic Differentiation of Mesenchymal Stem Cells
      Using Magnetic Nanoparticles.
AB  - Chondrogenic commitments of mesenchymal stem cells (MSCs) require 3D cellular
      organization. Furthermore, recent progresses in bioreactor technology have
      contributed to the development of various biophysical stimulation platforms for
      efficient cartilage tissue formation. Here, an approach is reported to drive 3D
      cellular organization and enhance chondrogenic commitment of bone-marrow-derived
      human mesenchymal stem cells (BM-hMSCs) via magnetic nanoparticle (MNP)-mediated
      physical stimuli. MNPs isolated from Magnetospirillum sp. AMB-1 are endocytosed
      by the BM-hMSCs in a highly efficient manner. MNPs-incorporated BM-hMSCs are
      pelleted and then subjected to static magnetic field and/or magnet-derived shear
      stress. Magnetic-based stimuli enhance level of sulfated glycosaminoglycan (sGAG)
      and collagen synthesis, and facilitate the chondrogenic differentiation of BM
      hMSCs. In addition, both static magnetic field and magnet-derived shear stress
      applied for the chondrogenic differentiation of BM-hMSCs do not show increament
      of hypertrophic differentiation. This MNP-mediated physical stimulation platform
      demonstrates a promising strategy for efficient cartilage tissue engineering. 

PMID- 25846520
TI  - Right and left inverted lobar lung transplantation.
AB  - Adult recipients frequently withdraw from living-donor lobar lung transplantation
      because of the small size of donor grafts. The right lower lobe is 120% larger
      than the left lower lobe. We developed a novel surgical technique in which an
      inverted right lower lobe graft can be transplanted into the left thorax. The
      first patient was a 43-year-old woman with end-stage idiopathic interstitial
      pneumonia. Her husband was the only eligible donor for living-donor lobar lung
      transplantation. His right lower lobe was estimated to provide 45% of the
      recipient's predicted forced vital capacity, which would provide the borderline
      function required for living-donor lobar lung transplantation. Since lung
      perfusion scintigraphy of the recipient showed a right-to-left ratio of 64:36,
      transplanting the right lower lobe graft into the left thorax and sparing the
      native right lung was considered the only treatment option. We simulated this
      procedure using three-dimensional models produced by a three-dimensional printer.
      In living-donor lobar lung transplantation, all anastomoses were performed
      smoothly as planned preoperatively. Because of the initial success, this
      procedure was performed successfully in two additional patients. This procedure
      enables larger grafts to be transplanted, potentially solving critical size
      matching problems in living-donor lobar lung transplantation. 

PMID- 25846519
TI  - Survival in relation to hospital type after resection or sorafenib treatment for
      hepatocellular carcinoma in The Netherlands.
AB  - BACKGROUND AND OBJECTIVE: Despite an increase in recent years, hepatocellular
      carcinoma remains uncommon in the Netherlands. The aim of the current study is to
      explore potential effects of hospital type and volume on outcomes after resection
      or sorafenib in patients with hepatocellular carcinoma. METHODS: Initial
      treatment and survival of patients with hepatocellular carcinoma diagnosed in the
      period 2005-2011 were based on data of the Netherlands Cancer Registration.
      Potential risk factors (including hospital type and volume) for 30-days
      postoperative and long-term mortality in patients who underwent resection and in
      patients treated with sorafenib were evaluated by uni- and multivariate analyses.
      RESULTS: In the period 2005-2011, 2402 patients were diagnosed with
      hepatocellular carcinoma: 12% received resection and 9% sorafenib. Postoperative
      mortality was higher in non-university hospitals (13% versus 4%; P=0.01).
      Resection in non-university hospitals was associated with higher postoperative
      mortality (odds ratio 3.38, 95% confidence interval 1.37-10.68) and long-term
      mortality (hazard ratio 1.21, 95% confidence interval 1.04-1.40). Sorafenib
      treatment in non-university hospitals was also associated with higher long-term
      mortality (hazard ratio 1.39, 95% confidence interval 1.06-1.82). Hospital volume
      was not independent predictor for outcome. CONCLUSION: In low incidence
      countries, outcome after resection or sorafenib for hepatocellular carcinoma may
      differ between various hospital types.

PMID- 25846521
TI  - ICU physician staffing: what else do we need to know?

PMID- 25846522
TI  - COPD: undefeated!

PMID- 25846523
TI  - Medical thoracoscopy: the green shapes of grey.

PMID- 25846524
TI  - POINT: should radiation dose from CT scans be a factor in patient care? Yes.

PMID- 25846525
TI  - COUNTERPOINT: should radiation dose from CT scans be a factor in patient care?
      No.

PMID- 25846526
TI  - Rebuttal from Dr McCunney.

PMID- 25846527
TI  - Rebuttal from Dr Doss.

PMID- 25846528
TI  - Systolic and mean pulmonary artery pressures: are they interchangeable in
      patients with pulmonary hypertension?
AB  - Pulmonary hypertension (PH) is a common complication of numerous diseases,
      including left-sided heart diseases and chronic lung diseases and/or hypoxia,
      where PH is associated with exercise limitation and a worse prognosis. Other
      forms of PH include pulmonary arterial hypertension (PAH), chronic thromboembolic
      PH (CTEPH), and PH with unclear multifactorial mechanisms. Over the past decade,
      it has been documented that systolic pulmonary artery pressure (sPAP) may help
      estimate mean pulmonary artery pressure (mPAP) in adults with high accuracy and
      reasonably good precision (mPAP = 0.61 sPAP + 2 mm Hg). This strong linear
      relationship between sPAP and mPAP was unexpected from a classic physiologic
      point of view. Consistent results have been obtained from independent teams using
      either high-fidelity micromanometer-tipped PA catheters or fluid-filled
      catheters. Overall, the strong link between sPAP and mPAP has been documented
      over a wide range of PAPs, heart rate, cardiac output, wedge pressure, and causes
      of PH, during changes in posture and activity, and irrespective of patient's sex,
      age, and BMI. A review of available invasive data confirms that patients with
      CTEPH and idiopathic PAH matched for their mPAP exhibit essentially similar sPAP.
      Pressure redundancy may be explained by the dependence of PA compliance upon
      mPAP. The 25 mm Hg threshold used to define PH accurately corresponds to an sPAP
      of 38 mm Hg. Although the limits of the echocardiographic estimation of sPAP are
      widely documented, results from invasive studies may furnish an evidence-based
      sPAP-derived mPAP value, potentially useful in the multiparameter
      echocardiographic approach currently used to diagnose and follow patients with
      PH. 

PMID- 25846529
TI  - Drug resistance in Mycobacterium tuberculosis: molecular mechanisms challenging
      fluoroquinolones and pyrazinamide effectiveness.
AB  - Physicians are more and more often challenged by difficult-to-treat cases of TB.
      They include patients infected by strains of Mycobacterium tuberculosis that are
      resistant to at least isoniazid and rifampicin (multidrug-resistant TB) or to at
      least one fluoroquinolone (FQ) and one injectable, second-line anti-TB drug in
      addition to isoniazid and rifampicin (extensively drug-resistant TB). The drug
      treatment of these cases is very long, toxic, and expensive, and, unfortunately,
      the proportion of unsatisfactory outcomes is still considerably high. Although
      FQs and pyrazinamide (PZA) are backbone drugs in the available anti-TB regimens,
      several uncertainties remain about their mechanisms of action and even more
      remain about the mechanisms leading to drug resistance. From a clinical point of
      view, a better understanding of the genetic basis of drug resistance will aid (1)
      clinicians to provide quality clinical management to both drug-susceptible and
      drug-resistant TB cases (while preventing emergence of further resistance), and
      (2) developers of new molecular-based diagnostic assays to better direct their
      research efforts toward a new generation of sensitive, specific, cheap, and easy
      to-use point-of-care diagnostics. In this review we provide an update on the
      molecular mechanisms leading to FQ- and PZA-resistance in M tuberculosis. 

PMID- 25846530
TI  - The uncommon case of Jahi McMath.
AB  - A 13-year-old patient named Jahi McMath was determined to be dead by neurologic
      criteria following cardiopulmonary arrest and resuscitation at a hospital in
      Oakland, California. Her family did not agree that she was dead and refused to
      allow her ventilator to be removed. The family's attorney stated in the media
      that families, rather than physicians, should decide whether patients are dead
      and argued in the courts that the families' constitutional rights of religion and
      privacy would be violated otherwise. Ultimately, a judge agreed that the patient
      was dead in keeping with California law, but the constitutional issue was
      undecided. The patient was then transferred to a hospital in New Jersey, a state
      whose laws allow families to require on religious grounds that death be
      determined by cardiopulmonary criteria. Although cases such as this are uncommon,
      they demonstrate public confusion about the concept of neurologic death and the
      rejection of this concept by some families. The confusion may be caused in part
      by a lack of uniformity in state laws regarding the legal basis of death, as
      reflected in the differences between New Jersey and California statutes. Families
      who reject the determination of death by neurologic criteria on religious grounds
      should be given reasonable accommodation in all states, but society should not
      pay for costly treatments for patients who meet these criteria unless the state
      requires it, as only New Jersey does. Laws that give physicians the right to
      determine death by neurologic criteria in other states probably can survive a
      constitutional challenge. Physicians and hospitals faced with similar cases in
      the future should follow state laws and work through the courts if necessary. 

PMID- 25846531
TI  - Capturing structured, pulmonary disease-specific data elements in electronic
      health records.
AB  - Electronic health records (EHRs) have the potential to improve health-care
      quality by allowing providers to make better decisions at the point of care based
      on electronically aggregated data and by facilitating clinical research. These
      goals are easier to achieve when key, disease-specific clinical information is
      documented as structured data elements (SDEs) that computers can understand and
      process, rather than as free-text/natural-language narrative. This article
      reviews the benefits of capturing disease-specific SDEs. It highlights several
      design and implementation considerations, including the impact on efficiency and
      expressivity of clinical documentation and the importance of adhering to data
      standards when available. Pulmonary disease-specific examples of collection
      instruments are provided from two commonly used commercial EHRs. Future
      developments that can leverage SDEs to improve clinical quality and research are
      discussed. 

PMID- 25846532
TI  - Air pollution exposure: a novel environmental risk factor for interstitial lung
      disease?
AB  - Air pollution exposure is a well-established risk factor for several adverse
      respiratory outcomes, including airways diseases and lung cancer. Few studies
      have investigated the relationship between air pollution and interstitial lung
      disease (ILD) despite many forms of ILD arising from environmental exposures.
      There are potential mechanisms by which air pollution could cause, exacerbate, or
      accelerate the progression of certain forms of ILD via pulmonary and systemic
      inflammation as well as oxidative stress. This article will review the current
      epidemiologic and translational data supporting the plausibility of this
      relationship and propose a new conceptual framework for characterizing novel
      environmental risk factors for these forms of lung disease. 

PMID- 25846533
TI  - ICU director data: using data to assess value, inform local change, and relate to
      the external world.
AB  - Improving value within critical care remains a priority because it represents a
      significant portion of health-care spending, faces high rates of adverse events,
      and inconsistently delivers evidence-based practices. ICU directors are
      increasingly required to understand all aspects of the value provided by their
      units to inform local improvement efforts and relate effectively to external
      parties. A clear understanding of the overall process of measuring quality and
      value as well as the strengths, limitations, and potential application of
      individual metrics is critical to supporting this charge. In this review, we
      provide a conceptual framework for understanding value metrics, describe an
      approach to developing a value measurement program, and summarize common metrics
      to characterize ICU value. We first summarize how ICU value can be represented as
      a function of outcomes and costs. We expand this equation and relate it to both
      the classic structure-process-outcome framework for quality assessment and the
      Institute of Medicine's six aims of health care. We then describe how ICU leaders
      can develop their own value measurement process by identifying target areas,
      selecting appropriate measures, acquiring the necessary data, analyzing the data,
      and disseminating the findings. Within this measurement process, we summarize
      common metrics that can be used to characterize ICU value. As health care, in
      general, and critical care, in particular, changes and data become more
      available, it is increasingly important for ICU leaders to understand how to
      effectively acquire, evaluate, and apply data to improve the value of care
      provided to patients. 

PMID- 25846535
TI  - An addition was made to the abstract: the association of direct thrombin
      inhibitor anticoagulants with cardiac thromboses.

PMID- 25846536
TI  - Diffuse alveolar damage in a patient receiving dronedarone.
AB  - Dronedarone is an amiodarone-like antiarrhythmic with a modified structure. The
      addition of a methyl sulfonyl group theoretically reduces the toxicity of
      amiodarone, specifically, adverse thyroid and pulmonary effects. Although animal
      studies have implicated dronedarone as a cause of lung injury, to date controlled
      trials in humans have not demonstrated an association. A 68-year-old woman
      developed a dry cough and worsening respiratory distress after receiving
      dronedarone for 6 months. Discontinuation of dronedarone therapy and subsequent
      steroid therapy led to a dramatic improvement of symptoms. Dronedarone may be
      associated with interstitial lung disease. We believe that patients receiving
      dronedarone should have their diffusing capacity of lung for carbon monoxide and
      lung volumes monitored prior to initiation of therapy and frequently thereafter. 

PMID- 25846537
TI  - Isolated pauciimmune pulmonary capillaritis successfully treated with rituximab.
AB  - Diffuse alveolar hemorrhage (DAH) is a syndrome caused by different mechanisms,
      including capillary stress failure, diffuse alveolar damage, and capillaritis.
      Capillaritis is the most common cause and is often associated with systemic
      autoimmune disorders, most commonly antineutrophilic cytoplasmic antibody
      associated vasculitis. The occurrence of DAH with underlying pulmonary
      capillaritis but without clinical or serologic findings of an associated
      underlying systemic disorder is known as isolated pauciimmune pulmonary
      capillaritis (IPPC), and only eight cases have been described in the literature.
      The mainstay of treatment of this rare condition has been cyclophosphamide and
      glucocorticoids. When cases are unresponsive to cyclophosphamide, there is no
      known alternative treatment. Herein, we describe a case of IPPC that failed
      cyclophosphamide treatment with recurrent DAH. Rituximab therapy was then
      initiated with no further evidence of recurrence. This case report suggests that
      rituximab could be considered an alternative therapy to induce remission in
      patients with IPPC. 

PMID- 25846534
TI  - The pathophysiology of insomnia.
AB  - Insomnia disorder is characterized by chronic dissatisfaction with sleep quantity
      or quality that is associated with difficulty falling asleep, frequent nighttime
      awakenings with difficulty returning to sleep, and/or awakening earlier in the
      morning than desired. Although progress has been made in our understanding of the
      nature, etiology, and pathophysiology of insomnia, there is still no universally
      accepted model. Greater understanding of the pathophysiology of insomnia may
      provide important information regarding how, and under what conditions, the
      disorder develops and is maintained as well as potential targets for prevention
      and treatment. The aims of this report are (1) to summarize current knowledge on
      the pathophysiology of insomnia and (2) to present a model of the pathophysiology
      of insomnia that considers evidence from various domains of research. Working
      within several models of insomnia, evidence for the pathophysiology of the
      disorder is presented across levels of analysis, from genetic to molecular and
      cellular mechanisms, neural circuitry, physiologic mechanisms, sleep behavior,
      and self-report. We discuss the role of hyperarousal as an overarching theme that
      guides our conceptualization of insomnia. Finally, we propose a model of the
      pathophysiology of insomnia that integrates the various types of evidence
      presented. 

PMID- 25846538
TI  - A 66-year-old woman with fever, cough, and a tongue lesion.
AB  - A 66-year-old woman presented with acute onset of fever, chills, and productive
      cough associated with right-sided chest pain. During a recent hospitalization for
      dyspnea, she had been diagnosed with Coombs-positive autoimmune hemolytic anemia
      and had been taking a tapering dose of prednisone starting approximately 6 weeks
      prior to admission. In the interim, her dyspnea had resolved on treatment with
      steroids. At the time of presentation, her prednisone dose was 40 mg. Additional
      medical history included VTE, for which the patient was receiving anticoagulation
      therapy, and steroid-induced diabetes mellitus. Many years earlier, she had been
      treated for TB in her home country. The patient had immigrated to Queens, New
      York, from a Nepalese village 8 years prior. While still in Nepal, she had worked
      on a farm and had been in close proximity to cows. In Queens, she lived with her
      family in a house with a small garden but had no pets. Recent travel included a
      visit to Nepal 9 months ago and a trip to Syracuse, New York, one month prior to
      presentation. She was a never smoker and did not consume alcohol. 

PMID- 25846539
TI  - A 15-year-old boy with snoring and molar tooth sign.
AB  - A 15-year-old boy presented for evaluation of snoring and sleep-disordered
      breathing. The parents noted that the patient snored every night and that he had
      episodes when he stopped breathing, ending with gasping for air. He had no
      history of sleep walking, night terrors, tongue biting, or seizures. The patient
      had two healthy siblings, but he had a history of intellectual disability and
      developmental delay. The patient had a history of adenotonsillectomy. 

PMID- 25846540
TI  - A 3-month-old infant with recurrent apparent life-threatening events in a car
      seat.
AB  - A 3-month-old infant was brought to clinic for evaluation of recurrent apparent
      life-threatening events (ALTEs). Two ALTE episodes occurred while the infant was
      sleeping in a safety car seat. The first one occurred when he was 4 weeks old.
      His mother noticed that he was not breathing; he appeared limp with full body
      cyanosis. His mother picked him up from the car seat, and he started breathing
      spontaneously and without any sign of distress. His skin color returned to
      normal. He was evaluated at the ED where the physical examination was normal. He
      was hospitalized 1 day for observation. During this time, workup, including ECG
      and chest radiograph, was normal. The parents were instructed on
      cardiorespiratory resuscitation and recommended to change car seats. The infant
      was discharged with an apnea monitor. He wore the apnea monitor while in the car
      seat. A second similar episode occurred at 10 weeks of age for which he was seen
      at the ED and referred to our clinic for further evaluation. Neither episode was
      related to feeding. 

PMID- 25846541
TI  - The critical flaw in physician compensation is not the sustainable growth rate!

PMID- 25846542
TI  - Response.

PMID- 25846543
TI  - How is TB transmitted?

PMID- 25846544
TI  - Response.

PMID- 25846545
TI  - Idiopathic pulmonary arterial hypertension in Asians: a long-term study on
      clinical outcomes.

PMID- 25846546
TI  - Racial and sex differences in presentation and outcomes of small cell lung cancer
      in the United States: 1973 to 2010.

PMID- 25846548
TI  - Increased risk of hepatocellular carcinoma in chronic hepatitis B patients with
      new onset diabetes: a nationwide cohort study.
AB  - BACKGROUND: Diabetes increases the risk of hepatocellular carcinoma (HCC),
      however, the time-relationship between hepatitis B virus and diabetes for the
      development of HCC remains unclear. AIM: To explore the risk of HCC in chronic
      hepatitis B patients with newly diagnosed diabetes. METHODS: We conducted a
      nationwide cohort study by using Taiwanese National Health Insurance Research
      Database, which covers over 99% of entire population. Among randomly sampled one
      million enrollees, 14 523 chronic hepatitis B patients were diagnosed in years
      1997-2009. We defined new onset diabetes as patients who were given the diagnosis
      in the years 1999-2009, but not in 1997-1998. The cohorts of chronic hepatitis B
      with new onset diabetes (n = 2099) and 1:1 ratio age-, gender- and inception
      point (onset date of diabetes)- matched nondiabetes (n = 2080) were followed up
      from the inception point until development of HCC, withdrawal from insurance or
      December 2009. RESULTS: After adjustment for competing mortality, patients with
      new onset diabetes had a significantly higher cumulative incidence of HCC
      [relative risk = 1.628, 95% confidence interval (CI) = 1.114-2.378, modified log
      rank test, P = 0.012] as compared to nondiabetes patients. After adjustment for
      age, gender, hyperlipidaemia, chronic hepatitis B treatment, statins therapy,
      cirrhosis, comorbidity index and obesity, diabetes was still an independent
      predictor for HCC (hazard ratio = 1.798, 95% CI = 1.194-2.707, P = 0.005).
      CONCLUSION: Chronic hepatitis B patients with newly diagnosed diabetes have an
      increased risk of hepatocellular carcinoma over time.

PMID- 25846547
TI  - Patients with reduced heart rate response to adenosine infusion have low
      myocardial flow reserve in (13)N-ammonia PET studies.
AB  - To assess the effect of adenosine infusion by evaluating the relationship between
      heart rate (HR) response to adenosine and myocardial flow reserve (MFR) of remote
      regions supplied by normal coronary arteries in (13)N-ammonia PET. Thirty-one
      consecutive subjects (20 known coronary artery disease patients, 4 chronic heart
      failure patients, and 7 normal volunteers) except cases having 3-vessel disease
      underwent rest and adenosine stress (13)N-ammonia myocardial perfusion PET. Semi
      quantitative, quantitative, and gated analyses were performed. Subjects were
      divided into two groups with regard to HR response to adenosine. Twenty-two
      subjects had normal HR response (peak/rest HR > 1.20), while reduced HR response
      (<= 1.20) was observed in nine subjects. There were no differences in rest
      myocardial blood flow (MBF) of remote regions between the groups. Subjects with
      reduced HR response had significantly lower stress MBF and MFR of remote regions
      than those with normal HR response (stress MBF: 1.559 +/- 0.517 vs. 2.279 +/-
      0.530, p = 0.004, MFR: 1.59 +/- 0.36 vs. 2.35 +/- 0.53, p = 0.001). There were no
      significant differences between the groups by means of semi-quantitative scoring.
      Rest and stress ejection fraction (EF) in the reduced HR response group was lower
      than that in the normal HR response group. In a multiple stepwise regression
      analysis, HR ratio, dyslipidemia, and Brinkman index were identified as
      predictors of the change in MFR of remote regions. Subjects with reduced HR
      response to adenosine had lower stress MBF and MFR of remote regions and lower
      EF. Moreover, HR response was one of the predictors of the change in MFR of
      remote regions.

PMID- 25846549
TI  - Therapeutic Use of Music and Television in Neurocritical Care: A Practice Survey.
AB  - INTRODUCTION: Although health care providers often play music via radio, or play
      television, to calm and soothe patients, limited research is available to guide
      practice. METHOD: This study used a 17-item practice survey that was distributed
      electronically to neurocritical care society members in July 2014. Responses were
      collated and analyzed using SAS (Version 9.3). RESULTS: There were 118 completed
      responses, including from 71 attending physicians, 9 resident or fellow
      physicians, 30 nurses, and 8 affiliate professional members. The majority of
      respondents sometimes or always play music (65%) and agree that music is
      therapeutic (70%). However, there was no clear practice pattern regarding when or
      why music or TV should be used as an intervention in the neurocritical care unit.
      CONCLUSION: The use of music and TV is a common intervention in the neurocritical
      care unit but lacks a strong scientific foundation and is associated with a high
      practice variance.

PMID- 25846550
TI  - Snack and Relax(r): A Strategy to Address Nurses' Professional Quality of Life.
AB  - PURPOSE AND DESIGN: Snack and Relax(r) (S&R), a program providing healthy snacks
      and holistic relaxation modalities to hospital employees, was evaluated for
      immediate impact. A cross-sectional survey was then conducted to assess the
      professional quality of life (ProQOL) in registered nurses (RNs); compare S&R
      participants/nonparticipants on compassion satisfaction (CS), burnout, and
      secondary traumatic stress (STS); and identify situations in which RNs
      experienced compassion fatigue or burnout and the strategies used to address
      these situations. METHOD: Pre- and post vital signs and self-reported stress were
      obtained from S&R attendees (N = 210). RNs completed the ProQOL Scale measuring
      CS, burnout, and STS (N = 158). FINDINGS: Significant decreases in self-reported
      stress, respirations, and heart rate were found immediately after S&R. Low CS was
      noted in 28.5% of participants, 25.3% had high burnout, and 23.4% had high STS.
      S&R participants and nonparticipants did not differ on any of the ProQOL scales.
      Situations in which participants experienced compassion fatigue/burnout were
      categorized as patient-related, work-related, and personal/family-related.
      Strategies to address these situations were holistic and stress reducing.
      CONCLUSION: Providing holistic interventions such as S&R for nurses in the
      workplace may alleviate immediate feelings of stress and provide a moment of
      relaxation in the workday.

PMID- 25846551
TI  - Profiling cancer gene mutations in longitudinal epithelial ovarian cancer
      biopsies by targeted next-generation sequencing: a retrospective study.
AB  - BACKGROUND: The majority of patients with stage III-IV epithelial ovarian cancer
      (EOC) relapse after initially responding to platinum-based chemotherapy, and
      develop resistance. The genomic features involved in drug resistance are unknown.
      To unravel some of these features, we investigated the mutational profile of
      genes involved in pathways related to drug sensitivity in a cohort of matched
      tumors obtained at first surgery (Ft-S) and second surgery (Sd-S). PATIENTS AND
      METHODS: Matched biopsies (33) taken at Ft-S and Sd-S were selected from the
      'Pandora' tumor tissue collection. DNA libraries for 65 genes were generated
      using the TruSeq Custom Amplicon kit and sequenced on MiSeq (Illumina). Data were
      analyzed using a high-performance cluster computing platform (Cloud4CARE project)
      and independently validated. RESULTS: A total of 2270 somatic mutations were
      identified (89.85% base substitutions 8.19% indels, and 1.92% unknown).
      Homologous recombination (HR) genes and TP53 were mutated in the majority of Ft
      S, while ATM, ATR, TOP2A and TOP2B were mutated in the entire dataset. Only 2% of
      mutations were conserved between matched Ft-S and Sd-S. Mutations detected at
      second surgery clustered patients in two groups characterized by different
      mutational profiles in genes associated with HR, PI3K, miRNA biogenesis and
      signal transduction. CONCLUSIONS: There was a low level of concordance between Ft
      S and Sd-S in terms of mutations in genes involved in key processes of tumor
      growth and drug resistance. This result suggests the importance of future
      longitudinal analyses to improve the clinical management of relapsed EOC.

PMID- 25846553
TI  - Reply to the letter to the editor 'potential clinical relevant drug-drug
      interactions: comparison between different compendia, do we have a validated
      method?' by Conde-Estevez et al.

PMID- 25846552
TI  - Sunitinib 2 weeks on, 1 off: strengths and weaknesses.

PMID- 25846555
TI  - Alternative sunitinib schedules in metastatic renal cell carcinoma and the
      RAINBOW study.

PMID- 25846554
TI  - High level of chromosomal instability in circulating tumor cells of ROS1
      rearranged non-small-cell lung cancer.
AB  - BACKGROUND: Genetic aberrations affecting the c-ros oncogene 1 (ROS1) tyrosine
      kinase gene have been reported in a small subset of patients with non-small-cell
      lung cancer (NSCLC). We evaluated whether ROS1-chromosomal rearrangements could
      be detected in circulating tumor cells (CTCs) and examined tumor heterogeneity of
      CTCs and tumor biopsies in ROS1-rearranged NSCLC patients. PATIENTS AND METHODS:
      Using isolation by size of epithelial tumor cells (ISET) filtration and filter
      adapted-fluorescence in situ hybridization (FA-FISH), ROS1 rearrangement was
      examined in CTCs from four ROS1-rearranged patients treated with the ROS1
      inhibitor, crizotinib, and four ROS1-negative patients. ROS1-gene alterations
      observed in CTCs at baseline from ROS1-rearranged patients were compared with
      those present in tumor biopsies and in CTCs during crizotinib treatment.
      Numerical chromosomal instability (CIN) of CTCs was assessed by DNA content
      quantification and chromosome enumeration. RESULTS: ROS1 rearrangement was
      detected in the CTCs of all four patients with ROS1 rearrangement previously
      confirmed by tumor biopsy. In ROS1-rearranged patients, median number of ROS1
      rearranged CTCs at baseline was 34.5 per 3 ml blood (range, 24-55). In ROS1
      negative patients, median background hybridization of ROS1-rearranged CTCs was
      7.5 per 3 ml blood (range, 7-11). Tumor heterogeneity, assessed by ROS1 copy
      number, was significantly higher in baseline CTCs compared with paired tumor
      biopsies in the three patients experiencing PR or SD (P < 0.0001). Copy number in
      ROS1-rearranged CTCs increased significantly in two patients who progressed
      during crizotinib treatment (P < 0.02). CTCs from ROS1-rearranged patients had a
      high DNA content and gain of chromosomes, indicating high levels of aneuploidy
      and numerical CIN. CONCLUSION: We provide the first proof-of-concept that CTCs
      can be used for noninvasive and sensitive detection of ROS1 rearrangement in
      NSCLC patients. CTCs from ROS1-rearranged patients show considerable
      heterogeneity of ROS1-gene abnormalities and elevated numerical CIN, a potential
      mechanism to escape ROS1-inhibitor therapy in ROS1-rearranged NSCLC tumors.

PMID- 25846556
TI  - Single active-site mutants are sufficient to enhance serine:pyruvate alpha
      transaminase activity in an omega-transaminase.
AB  - We have analyzed the natural evolution of transaminase structure and sequence
      between an alpha-transaminase serine-pyruvate aminotransferase and an omega
      transaminase from Chromobacterium violaceum with < 20% sequence identity, and
      identified the active-site regions that are least conserved structurally. We also
      show that these structural changes correlate strongly with transaminase substrate
      specificity during evolution and therefore might normally be presumed to be
      essential determinants of substrate specificity. However, key residues are often
      conserved spatially during evolution and yet originate from within a different
      region of the sequence via structural reorganizations. In the present study, we
      also show that alpha-transaminase-type serine-pyruvate aminotransferase activity
      can be engineered into the CV2025 omega-transaminase scaffold with any one of
      many possible single-point mutations at three key positions, without the
      requirement for significant backbone remodeling, or repositioning of the residue
      from a different region of sequence. This finding has significant implications
      for enzyme redesign in which solutions to substrate specificity changes may be
      found more efficiently than is achieved by engineering in all sequence and
      structure determinants identified by correlation to substrate specificity.

PMID- 25846557
TI  - Cost attributable to Fetal Alcohol Spectrum Disorder in the Canadian correctional
      system.
AB  - Prenatal alcohol exposure is the leading identifiable cause of intellectual
      disability in the Western world and may result in Fetal Alcohol Spectrum Disorder
      (FASD). Individuals with FASD have a higher risk of being involved in the legal
      system, either as offenders or as victims. Therefore, the aim of the current
      study was to estimate the direct cost for youths (12-17 years old) and adults
      (18+ years old) with FASD to the Canadian correctional system in 2011/2012. The
      prevalence of FASD in the Canadian correctional system, obtained from the current
      epidemiological literature, was applied to the average number of youths and
      adults in the correctional system in 2011/2012. The average daily cost for
      corrections was then applied to the estimated number of youths and adults with
      FASD in custody. The cost of corrections among youths with FASD in Canada in
      2011/2012 was calculated to be approximately $17.5M Canadian dollars (CND; $13.6M
      CND for males and $3.8M CND for females) and among adults with FASD was estimated
      to be about $356.2M CND ($140M CND for provincial and territorial custody and
      $216.2M CND for federal custody). The study findings emphasize the need to raise
      awareness regarding the prevalence of FASD in the correctional system. It is
      crucial to incorporate FASD screening and intervention strategies as early as
      possible in the criminal justice process.

PMID- 25846558
TI  - Seclusion and the importance of contextual factors: An innovation project
      revisited.
AB  - Variation in seclusion rates between psychiatric facilities cannot be adequately
      explained by patient characteristics alone and there is a growing awareness of
      the influence of 'cultural' and staff factors on the use of seclusion. In this
      study, staff variables as well as seclusion parameters were investigated during
      the implementation of an innovation project, against the background of an
      institutional program to reduce the use of coercive measures. The results
      demonstrate the impact of confidence within the team, staffing level and
      communication with the patient on nurses' decisions on seclusion. The importance
      of the organizational context is further illustrated by the negative effects of
      organizational instability on nurses' attitudes and decision making with respect
      to seclusion, and on seclusion rates. A reduction in the use of seclusion was
      achieved after the implementation of the innovation project; however, during a
      period of organizational turmoil, the work engagement scores of staff decreased
      and the use of seclusion increased. The results of this study show the
      vulnerability of innovations within the continuously changing organizational
      context of mental health care. 

PMID- 25846559
TI  - Virus disease in wheat predicted to increase with a changing climate.
AB  - Current atmospheric CO2 levels are about 400 MUmol mol(-1) and are predicted to
      rise to 650 MUmol mol(-1) later this century. Although the positive and negative
      impacts of CO2 on plants are well documented, little is known about interactions
      with pests and diseases. If disease severity increases under future environmental
      conditions, then it becomes imperative to understand the impacts of pathogens on
      crop production in order to minimize crop losses and maximize food production.
      Barley yellow dwarf virus (BYDV) adversely affects the yield and quality of
      economically important crops including wheat, barley and oats. It is transmitted
      by numerous aphid species and causes a serious disease of cereal crops worldwide.
      This study examined the effects of ambient (aCO2 ; 400 MUmol mol(-1) ) and
      elevated CO2 (eCO2 ; 650 MUmol mol(-1) ) on noninfected and BYDV-infected wheat.
      Using a RT-qPCR technique, we measured virus titre from aCO2 and eCO2 treatments.
      BYDV titre increased significantly by 36.8% in leaves of wheat grown under eCO2
      conditions compared to aCO2 . Plant growth parameters including height, tiller
      number, leaf area and biomass were generally higher in plants exposed to higher
      CO2 levels but increased growth did not explain the increase in BYDV titre in
      these plants. High virus titre in plants has been shown to have a significant
      negative effect on plant yield and causes earlier and more pronounced symptom
      expression increasing the probability of virus spread by insects. The combination
      of these factors could negatively impact food production in Australia and
      worldwide under future climate conditions. This is the first quantitative
      evidence that BYDV titre increases in plants grown under elevated CO2 levels.

PMID- 25846560
TI  - Tau immunotherapy for Alzheimer's disease.
AB  - Targeting pathological tau protein in Alzheimer's disease (AD) and related
      tauopathies has shown great potential in animal models. Given that tau lesions
      correlate better with the degree of dementia than do amyloid-beta (Abeta)
      plaques, their clearance may be clinically more efficacious than removing Abeta
      when cognitive deficits become evident in AD. Several complementary mechanisms of
      antibody-mediated removal of tau aggregates are likely to act in concert and the
      importance of each one may depend on antibody properties, the disease, and its
      stage. Clinical trials of tau immunotherapy are already underway and several more
      are likely to be initiated in the near future. 

PMID- 25846561
TI  - Obesity depresses baroreflex control of renal sympathetic nerve activity and
      heart rate in Sprague Dawley rats: role of the renal innervation.
AB  - AIM: This study investigated the role of the renal innervation in arterial and
      cardiopulmonary baroreflex regulation of renal sympathetic nerve activity (RSNA)
      and heart rate (HR) in rats fed a high-fat diet to induce obesity. METHODS: Rats
      received either a normal (12% kcal) or high (45% kcal) fat diet for 60 days. On
      day 61, rats were anesthetized and prepared for recording left RSNA. In one
      group, the renal nerves remained intact, while in the other, both kidneys were
      denervated. Baroreflex gain curves for RSNA and HR were generated by increasing
      and decreasing blood pressure. Low-pressure baroreceptors were challenged by
      infusing a saline load. RESULTS: Mean blood pressure was 135 mmHg in the fat-fed
      and 105 mmHg (P < 0.05) in normal rats. Weight gain, adiposity index and
      creatinine clearance were 37, 82 and 55% higher (P < 0.05-0.001), but urine flow
      rate and fractional sodium excretions were 53 and 65% (both P < 0.001) lower,
      respectively, in the fat-fed compared to normal rats. In fat-fed rats with
      innervated kidneys, RSNA and HR arterial baroreflex sensitivities were reduced by
      73 and 72% (both P < 0.05) but were normal in renally denervated rats. Volume
      expansion decreased RSNA by 66% (P < 0.001) in normal rats, but not in the intact
      fat-fed rats and by 51% (P < 0.01) in renally denervated fat-fed rats.
      CONCLUSION: Feeding a high-fat diet caused hypertension associated with
      dysregulation of the arterial and cardiopulmonary baroreflexes which was
      dependent on an intact renal innervation. This suggests that in obese states
      neural signals arising from the kidney contribute to a deranged autonomic
      control.

PMID- 25846562
TI  - Goldberg-Shprintzen megacolon syndrome with associated sensory motor axonal
      neuropathy.
AB  - Goldberg-Shprintzen megacolon syndrome (GOSHS) (OMIM 609460) is characterized by
      a combination of learning difficulties, characteristic dysmorphic features and
      Hirschsprung's disease. Variable clinical features include iris coloboma,
      congenital heart defects and central nervous system abnormalities, in particular
      polymicrogyria. GOSHS has been attributed to recessive mutations in KIAA1279,
      encoding kinesin family member (KIF)-binding protein (KBP) with a crucial role in
      neuronal microtubule dynamics. Here we report on a 7-year-old girl with GOSHS as
      a result of a homozygous deletion of exons 5 and 6 of the KIAA1279 gene. She had
      been referred with the suspicion of an underlying neuromuscular disorder before
      the genetic diagnosis was established, prompted by the findings of motor
      developmental delay, hypotonia, ptosis and absent reflexes. Neurophysiological
      studies revealed unequivocal evidence of a peripheral axonal sensory motor
      neuropathy. We hypothesize that an axonal sensory motor neuropathy may be part of
      the phenotypical spectrum of KIAA1279-related GOSHS, probably reflecting the
      effects of reduced KBP protein expression on peripheral neuronal function.

PMID- 25846563
TI  - Signal transducers and activators of transcription 3-induced metastatic potential
      in gastric cancer cells is enhanced by glycogen synthase kinase-3beta.
AB  - The transcription factor signal transducers and activators of transcription 3
      (STAT3) can promote cancer metastasis, but its underlying regulatory mechanisms
      in gastric cancer cell invasiveness still remain obscure. We investigated the
      relationship between STAT3 and glycogen synthase kinase-3beta (GSK-3beta) and its
      significance in metastatic potential in gastric cancer cells. Immunohistochemical
      tissue array analysis of 267 human gastric carcinoma specimens showed that the
      expressions of active forms of STAT3 (pSTAT3) and GSK-3beta (pGSK-3beta) were
      found in 68 (25%) and 124 (46%) of 267 gastric cancer cases, respectively,
      showing a positive correlation (p < 0.001). Cell culture experiments using
      gastric cancer cell lines SNU-638 and SNU-668 revealed that STAT3 suppression did
      not affect pGSK-3beta expression, whereas GSK-3beta inhibition reduced pSTAT3
      expression. With respect to metastatic potential in gastric cancer cells, both
      STAT3 suppression and GSK-3beta inhibition decreased cell migration, invasion,
      and mesenchymal marker (Snail, Vimentin, and MMP9) expression. Moreover, the
      inhibitory effects of STAT3 and GSK-3beta on cell migration were synergistic.
      These results demonstrated that STAT3 and GSK-3beta are positively associated and
      synergistically contribute to metastatic potential in gastric cancer cells. Thus,
      dual use of STAT3 and GSK-3beta inhibitors may enhance the efficacy of the anti
      metastatic treatment of gastric cancer. 

PMID- 25846564
TI  - Aspergillus nidulans flippase DnfA is cargo of the endocytic collar and plays
      complementary roles in growth and phosphatidylserine asymmetry with another
      flippase, DnfB.
AB  - Endocytosis and exocytosis are strictly segregated at the ends of hyphal cells of
      filamentous fungi, with a collar of endocytic activity encircling the growing
      cell tip, which elongates through directed membrane fusion. It has been proposed
      that this separation supports an endocytic recycling pathway that maintains polar
      localization of proteins at the growing apex. In a search for proteins in the
      filamentous fungus Aspergillus nidulans that possess an NPFxD motif, which
      signals for endocytosis, a Type 4 P-Type ATPase was identified and named DnfA.
      Interestingly, NPFxD is at a different region of DnfA than the same motif in the
      Saccharomyces cerevisiae ortholog, although endocytosis is dependent on this
      motif for both proteins. DnfA is involved in asexual sporulation and polarized
      growth. Additionally, it is segregated within the Spitzenkorper from another Type
      4 P-type ATPase, DnfB. Next, the phosphatidylserine marker GFP::Lact-C2 was
      expressed in growing hyphae, which revealed that this phospholipid is enriched on
      the cytosolic face of secretory vesicles. This distribution is affected by
      deleting either dnfA or dnfB. These findings provide evidence for the spatial and
      temporal segregation of Type4-ATPases in filamentous fungi, and the asymmetric
      distribution of phosphatidylserine to the Spitzenkorper in A. nidulans. 

PMID- 25846565
TI  - TDP-43 in amyotrophic lateral sclerosis - is it a prion disease?
AB  - Amyotrophic lateral sclerosis is a devastating disease characterized by rapidly
      progressive paresis. The neuropathological hallmark of most amyotrophic lateral
      sclerosis cases are neuronal and glial aggregates of phosphorylated 43-kDa TAR
      DNA-binding protein (pTDP-43). The accumulation of similar proteins into
      insoluble aggregates is now recognized as a common pathological hallmark of
      neurodegenerative diseases in general. Importantly, many of these proteins such
      as tau and amyloid-beta in Alzheimer's disease and alpha-synuclein in Parkinson's
      show a stereotypical sequential distribution pattern with progressing disease. In
      this review, we discuss recent evidence that TDP-43 in ALS may propagate
      similarly to other neurodegenerative disease proteins. We furthermore delineate
      similarities and important differences of TDP-43 proteinopathies to prion
      diseases. 

PMID- 25846566
TI  - Non-paraneoplastic ataxia in a patient with contactin-associated protein-2
      antibodies and benign course.

PMID- 25846567
TI  - Reversible cerebral vasoconstriction syndrome triggered by an electronic
      cigarette: case report.

PMID- 25846569
TI  - Diagnostic utility of microarray testing in pregnancy loss.
AB  - OBJECTIVES: To determine the frequency of clinically significant chromosomal
      abnormalities identified by chromosomal microarray in pregnancy losses at any
      gestational age and to compare microarray performance with that of traditional
      cytogenetic analysis when testing pregnancy losses. METHODS: Among 535 fetal
      demise specimens of any gestational age, clinical microarray-based comparative
      genomic hybridization (aCGH) was performed successfully on 515, and a subset of
      107 specimens underwent additional single nucleotide polymorphism (SNP) analysis.
      RESULTS: Overall, clinically significant abnormalities were identified in 12.8%
      (64/499) of specimens referred with normal or unknown karyotypes. Detection rates
      were significantly higher with earlier gestational age. In the subset with normal
      karyotype, clinically significant abnormalities were identified in 6.9% (20/288).
      This detection rate did not vary significantly with gestational age, suggesting
      that, unlike aneuploidy, the contribution of submicroscopic chromosomal
      abnormalities to fetal demise does not vary with gestational age. In the 107
      specimens that underwent aCGH and SNP analysis, seven cases (6.5%) had
      abnormalities of potential clinical significance detected by the SNP component,
      including female triploidy. aCGH failed to yield fetal results in 8.3%, which is
      an improvement over traditional cytogenetic analysis of fetal demise specimens.
      CONCLUSIONS: Both the provision of results in cases in which karyotype fails and
      the detection of abnormalities in the presence of a normal karyotype demonstrate
      the increased diagnostic utility of microarray in pregnancy loss. Thus,
      chromosomal microarray testing is a preferable, robust method of analyzing cases
      of pregnancy loss to better delineate possible genetic etiologies, regardless of
      gestational age.

PMID- 25846570
TI  - A study on the status of inflammatory systems in camels naturally infected with
      Toxoplasma gondii.
AB  - Toxoplasma gondii is a unique intracellular parasite with a worldwide
      distribution. This parasite infects a variety of cells in a wide range of animal
      species such as dromedary camels (Camelus dromedarius). In order to evaluate the
      pattern of possible changes in the blood level of some inflammatory mediators and
      antioxidant enzymes in camels infected with T. gondii, blood samples were taken
      from a total of 493 dromedary camels and serum concentrations of inflammatory
      mediators, acute phase proteins and antioxidant enzymes were measured. According
      to serological data, no seropositivity was found for anti-T. gondii IgM in serum
      samples; however, 49 camels (9.93 %) showed positive titrations for anti
      Toxoplasma IgG. The analyses of data in seropositive animals showed significant
      increases (P < 0.05) in the serum level of IL-1beta and adenosine deaminase
      activity; however, IFN-gamma and TNF-alpha demonstrated no significant changes in
      serum samples of the infected camels. In addition, while major acute phase
      proteins (haptoglobin (Hp) and serum amyloid A (SAA)) were markedly elevated in
      infected camels, the activity of antioxidant enzymes (SOD and GPX) was remarkably
      decreased in the blood samples of infected animals. Thus, during the chronic
      infection in camels, T. gondii can promote significant rises in concentrations of
      some cytokines (such as IL-1beta), acute phase proteins and adenosine deaminase. 

PMID- 25846571
TI  - A duplex PCR-based assay for simultaneous detection of Trypanosoma evansi and
      Theileria annulata infections in water buffaloes.
AB  - Trypanosomosis and bovine tropical theileriosis are important vector-borne
      protozoan diseases imposing some of the serious constraints on the health and
      productivity of domestic cattle in tropical and subtropical regions of the world.
      Following recovery from primary infection of both these conditions, animals
      become persistent carriers and act as reservoirs of infection thereby playing a
      critical role in disease epidemiology. The present study describes development
      and evaluation of duplex polymerase chain reaction (PCR) assays for simultaneous
      detection of Trypanosoma evansi and Theileria annulata in buffaloes. Following in
      silico screening for candidate target genes representing each of the pathogens,
      an optimized duplex PCR assay was established using TBR F/R and TAMS F/R as
      primer sets encoding for products of 164 and 721 bp for T. evansi and T.
      annulata, respectively. The results were compared and correlated with
      conventional Giemsa-stained thin blood smear examination and the single PCR
      assay. The duplex PCR detected each pathogen with the same level of sensitivity,
      irrespective of whether its DNA was amplified in isolation or together with DNA
      of another pathogen. Moreover, single and duplex PCRs were able to detect each
      species with equal sensitivity in serially diluted DNA representing mixtures of
      T. evansi and T. annulata, and no evidence of nonspecific amplification from
      nontarget species was observed. The developed assay may be seen as a good tool
      for epidemiological studies aiming at assessing the burden of dual infections and
      improving control of the associated diseases in endemic regions. 

PMID- 25846572
TI  - Effect of different levels of raw and heated grass pea seed (Lathyrus sativus) on
      nutrient digestibility, intestinal villus morphology and growth performance of
      broiler chicks.
AB  - This study aimed to investigate chemical composition and effect of different
      levels (0%, 10% and 20%) of raw grass pea (RGP) and heat-treated (120  degrees C
      for 30 min) grass pea seed (HGP) on nutrient digestibility, dressing percentage,
      relative internal organ weights, intestinal villous morphology and broiler
      chicks' performance. A total number of 200 day-old male chicks were raised under
      similar condition for 10 days. On day 11, chicks were randomly assigned to five
      dietary treatments and four replicates of 10 birds each. The result of chemical
      analysis indicated that Iranian grass pea seed has low levels of total and
      condensed tannin, and it may be considered as a good source of protein (36.1%)
      and energy (17.09 kJ GE/g). Heat treatment reduced (p < 0.05) the total and
      condensed tannin to 21% and 78% respectively. Grass peas seed had higher levels
      of nitrogen-free extract, P, Na, Mg and Zn than soya bean meal. The apparent
      digestibility of gross energy and lipid was affected (p < 0.01) by the treatment
      diets, and it was the lowest after feeding 20% of HGP (p < 0.05). The relative
      weight of breast and pancreas (p < 0.05) was affected by treatments. Percentage
      weight of breast and pancreas increased (p < 0.05) after feeding high levels
      (20%) of RGP and HGP. Substitution of 20% of RGP and HGP increased the duodenal
      crypt depth (p < 0.05); however, it had no suppressive effect on villus height as
      the absorptive surface of intestine. The feed conversion ratio was not affected
      by the treatments in the total experimental period. This study showed that,
      although the high level of grass pea seed caused a remarkable increase in the
      relative weight of pancreas and decreased the apparent digestibility of gross
      energy and lipid, it had beneficial effect on breast relative weight. It seems
      that heat processing is not effective method for improving quality of Iranian
      grass pea seed.

PMID- 25846573
TI  - Patient Education vs. Patient Experiences of Self-advocacy: Changing the
      Discourse to Support Cancer Survivors.
AB  - A growing emphasis on patient self-advocacy has emerged in the public discourse
      on cancer survivorship. This discourse shapes patients' conceptualizations about
      self-advocacy and in turn influences their health care attitudes and behaviors.
      The purpose of this discourse analysis is to explore the language of self
      advocacy by comparing a published self-advocacy guide with the lived experiences
      of women with ovarian cancer. Data sources include (1) a self-advocacy patient
      education guide published by the National Coalition for Cancer Survivorship and
      (2) transcripts of focus groups conducted with ovarian cancer survivors.
      Discourse analysis techniques were used to take a close look at the language used
      by both to uncover the meaning each group ascribed to self-advocacy. Challenges
      and inconsistencies were noted between the patient education guide and
      transcripts including viewing self-advocacy as a skill set to assert one's needs
      as opposed to a means by which to preserve a positive attitude and maintain a
      trusting relationship with health care providers, respectively. Some women saw
      themselves as self-advocates yet struggled to locate relevant health information
      and hesitated to upset their relationship with their health care providers. This
      analysis highlights tensions between the discourses and points to ways in which
      patient education materials can be adjusted to support cancer survivors in
      advocating for their needs according to their unique situations and preferences. 

PMID- 25846575
TI  - The effect of drug use disorder onset, remission or persistence on an
      individual's personal social network.
AB  - BACKGROUND AND OBJECTIVES: Drug use disorders (DUD) have strong associations with
      numerous social problems. However, little is known concerning differences between
      individuals who experience DUD onset, persistence or remission. While the
      literature is fairly clear on who is most likely to experience DUD onset and
      persistence, many correlates of DUD remission, including personal social
      networks, lack the empirical foundation to utilize them in evidence-based
      intervention or prevention efforts. While small, community samples suggest DUD
      remission is associated with growth in personal social networks, this conclusion
      is in need of larger population studies to justify. METHODS: This study used
      Waves 1 and 2 of the National Epidemiologic Study on Alcohol and Related
      Conditions (NESARC) to examine whether DUD status is a correlate of personal
      social networks. RESULTS: Multivariate models showed DUD onset and DUD
      persistence were related to smaller personal social networks. However,
      individuals who experience DUD remission showed personal social networks similar
      to persons who never experienced a DUD. DISCUSSION AND CONCLUSIONS: As one of the
      first empirical studies of personal social networks among individuals with
      different stages of DUD using nationally representative data, these findings
      suggest that by decreasing drug use, personal social networks may be increased,
      which is a strong trait associated with the social influence necessary with
      maintaining DUD recovery.

PMID- 25846574
TI  - Release of human cytomegalovirus from latency by a KAP1/TRIM28 phosphorylation
      switch.
AB  - Human cytomegalovirus (HCMV) is a highly prevalent pathogen that induces life
      long infections notably through the establishment of latency in hematopoietic
      stem cells (HSC). Bouts of reactivation are normally controlled by the immune
      system, but can be fatal in immuno-compromised individuals such as organ
      transplant recipients. Here, we reveal that HCMV latency in human CD34(+) HSC
      reflects the recruitment on the viral genome of KAP1, a master co-repressor,
      together with HP1 and the SETDB1 histone methyltransferase, which results in
      transcriptional silencing. During lytic infection, KAP1 is still associated with
      the viral genome, but its heterochromatin-inducing activity is suppressed by mTOR
      mediated phosphorylation. Correspondingly, HCMV can be forced out of latency by
      KAP1 knockdown or pharmacological induction of KAP1 phosphorylation, and this
      process can be potentiated by activating NFkB with TNF-alpha. These results
      suggest new approaches both to curtail CMV infection and to purge the virus from
      organ transplants. 

PMID- 25846576
TI  - Protection against Helicobacter pylori infection in BALB/c mice by oral
      administration of multi-epitope vaccine of CTB-UreI-UreB.
AB  - Chronic gastric infection by the Gram-negative bacterium Helicobacter pylori (H.
      pylori) is strongly associated with gastritis, gastric ulcer and the development
      of distal gastric carcinoma and gastric mucosal lymphoma in humans. Antibiotic
      treatment of H. pylori is becoming less effective because of increasing
      antibiotic resistance; other treatment approaches such as specifically targeted
      methods, etc. to destroy this organism would be beneficial. An epitope vaccine is
      a promising option for protection against H. pylori infection. In this study, a
      multi-epitope vaccine was constructed by linking cholera toxin B subunit (CTB),
      two antigenic fragments of H. pylori urease I subunit (UreI20-29, UreI98-107) and
      four antigenic fragments of H. pylori urease B subunit (UreB12-23, UreB229-251,
      UreB327-400, UreB515-561), resulting in the recombinant CTB-UreI-UreB (BIB). Its
      protective effect against H. pylori infection was evaluated in BALB/c mice.
      Significant protection against H. pylori challenge was achieved in BALB/c mice
      immunized with BIB (15/18, 83.3%), rIB plus rCTB (6/18, 33.3%) and rIB (2/18,
      11.1%) separately, while no protective effect was found in the mice immunized
      with either adjuvant rCTB alone or PBS. The induction of significant protection
      against H. pylori is possibly mediated by specific serum IgA and mucosal sIgA
      antibodies, and a mixed Th1/Th2/Th17 cells response. This multi-epitope vaccine
      might be a promising vaccine candidate that helps to control H. pylori infection.

PMID- 25846577
TI  - Treatment escalation options for patients with type 2 diabetes after failure of
      exenatide twice daily or glimepiride added to metformin: results from the
      prospective European Exenatide (EUREXA) study.
AB  - AIMS: To evaluate third-line thiazolidinedione (TZD) or glimepiride therapy in
      patients inadequately controlled on metformin + exenatide twice daily, and third
      line exenatide twice daily in patients inadequately controlled on metformin +
      glimepiride. METHODS: In this randomized, open-label, multicentre trial, 144
      patients with type 2 diabetes inadequately controlled [glycated haemoglobin
      (HbA1c) >9% (75 mmol/mol) after 3 months' treatment or >7% (53 mmol/mol) at two
      consecutive visits 3 months apart, after 6 months' treatment] on metformin +
      exenatide twice daily were re-randomized to add-on TZD or glimepiride, and 166
      patients inadequately controlled on metformin + glimepiride received add-on
      exenatide twice daily. Changes in HbA1c, body mass index (BMI), lipids,
      hypoglycaemia and vital signs were evaluated. RESULTS: The median duration of
      triple therapy was ~2 years. In patients inadequately controlled on metformin +
      exenatide twice daily, add-on TZD decreased HbA1c levels significantly better
      than add-on glimepiride: 130-week difference 0.48% [95% confidence interval (CI)
      0.19-0.77] or 5.2 mmol/mol (95% CI 2.1-8.4; p = 0.001), but with significantly
      increased BMI and systolic blood pressure. The ratio of documented symptomatic
      (blood glucose <=70 mg/dl [3.9 mmol/l]) hypoglycaemia rates for add-on
      glimepiride to add-on TZD was 8.48 (p < 0.0001). Add-on exenatide twice daily
      after metformin + glimepiride significantly reduced HbA1c levels: mean [standard
      deviation (s.d.)] change from baseline -0.35 (0.89)% [-3.8 (9.7) mmol/mol] and
      BMI: mean (s.d.) change from baseline -0.82 (1.9) kg/m(2) at 130 weeks, with a
      slightly increased rate of documented symptomatic hypoglycaemia from metformin +
      glimepiride (ratio 1.49). CONCLUSIONS: TZD, but not glimepiride, was an effective
      and well tolerated third-line therapy in patients without glycaemic control after
      long-term therapy with metformin + exenatide twice daily. Exenatide twice daily
      was an effective and well tolerated third-line therapy in patients inadequately
      controlled on metformin + glimepiride.

PMID- 25846578
TI  - Synthesis and characterization of nanosilver with antibacterial properties using
      Pinus densiflora young cone extract.
AB  - This study describes an eco-friendly, rapid method for green synthesis of silver
      nanoparticles (Ag NPs) from an aqueous solution of silver nitrate using Pinus
      densiflora for. multicaulis Uyeki young cone extract in a single-pot process.
      Color changes, ultraviolet-visible spectra (444.5 nm), X-ray diffraction peaks
      (2theta=39.68, 46.92, 68.12, and 79.10), and Fourier transform infrared
      spectroscopy (FT-IR) confirmed the presence of Ag NPs and phytochemicals.
      Transmission electron microscopy showed that the nanoparticles were mostly oval
      in shape, with a few triangular-shaped particles. Average particle size was 30-80
      nm. Phytochemicals present in the young pine cone extract were likely responsible
      for the reduction of Ag(+) ions. The synthesized Ag NPs (40 MUg) had a 7 mm
      larger zone of inhibition against the skin pathogen Brevibacterium linens than
      commercial Ag NPs, Propionibacterium acnes (14 mm), Bacillus cereus (9 mm) and
      Staphylococcus epidermidis (10mm).

PMID- 25846579
TI  - Vitamin D and ultraviolet phototherapy in Caucasians.
AB  - Ultraviolet B (UVB) radiation increases vitamin D level, but the influence of
      different UV sources (broadband and narrowband UVB lamps, solar simulators and
      sunbeds) and exposure durations have not been well characterized. In this study
      the influence of different UV sources on serum 25-hydroxyvitamin-D3 (25(OH)D3)
      levels in humans are reviewed. Serum 25(OH)D levels before and after UV exposure,
      and UV doses were extracted from 18 papers published in the past eight years. It
      was found that the UV dose-response curve for vitamin D generation in humans, as
      measured by the increments of serum 25(OH)D, is not linear with increasing UV
      doses and reaches a plateau at about 55 nmol/L after 4-5 weeks. About a half of
      this increase is equal to the difference between winter and summer 25(OH)D
      levels, and may be reached after 23 SEDs. The increments decrease with increasing
      baseline concentration of serum 25(OH)D, and the efficiency of only 0.7 nmol/L
      per SED is expected on the average when initial concentrations are higher than 50
      60 nmol/L. A whole body exposure to 2 SEDs of UVB radiation 3 times per week is
      expected to rise serum 25(OH)D with an initial rate of 3.9 nmol/L per SED,
      bringing a winter level of serum 25(OH)D up to a summer level.

PMID- 25846580
TI  - Oscillatory signatures of crossmodal congruence effects: An EEG investigation
      employing a visuotactile pattern matching paradigm.
AB  - Coherent percepts emerge from the accurate combination of inputs from the
      different sensory systems. There is an ongoing debate about the
      neurophysiological mechanisms of crossmodal interactions in the brain, and it has
      been proposed that transient synchronization of neurons might be of central
      importance. Oscillatory activity in lower frequency ranges (<30Hz) has been
      implicated in mediating long-range communication as typically studied in
      multisensory research. In the current study, we recorded high-density
      electroencephalograms while human participants were engaged in a visuotactile
      pattern matching paradigm and analyzed oscillatory power in the theta- (4-7Hz),
      alpha- (8-13Hz) and beta-bands (13-30Hz). Employing the same physical stimuli,
      separate tasks of the experiment either required the detection of predefined
      targets in visual and tactile modalities or the explicit evaluation of crossmodal
      stimulus congruence. Analysis of the behavioral data showed benefits for
      congruent visuotactile stimulus combinations. Differences in oscillatory dynamics
      related to crossmodal congruence within the two tasks were observed in the beta
      band for crossmodal target detection, as well as in the theta-band for congruence
      evaluation. Contrasting ongoing activity preceding visuotactile stimulation
      between the two tasks revealed differences in the alpha- and beta-bands. Source
      reconstruction of between-task differences showed prominent involvement of
      premotor cortex, supplementary motor area, somatosensory association cortex and
      the supramarginal gyrus. These areas not only exhibited more involvement in the
      pre-stimulus interval for target detection compared to congruence evaluation, but
      were also crucially involved in post-stimulus differences related to crossmodal
      stimulus congruence within the detection task. These results add to the
      increasing evidence that low frequency oscillations are functionally relevant for
      integration in distributed brain networks, as demonstrated for crossmodal
      interactions in visuotactile pattern matching in the current study. 

PMID- 25846582
TI  - Two alternative approaches to access mixed hydride-amido zinc complexes:
      synthetic, structural and solution implications.
AB  - Using bis(amide) Zn(HMDS)2 (HMDS = 1,1,1,3,3,3-hexamethyldisilazide) as a
      precursor, this study explores the synthesis of N-heterocyclic carbene stabilized
      mixed amido-hydride zinc complexes using two alternative hydride sources, namely
      dimethylamine borane (DMAB) and phenylsilane PhSiH3. Hydride-rich zinc cluster
      Zn4(HMDS)2H6.2IPr () (IPr = 1,3-bis(2,6-di-isopropylphenyl)imidazol-2-ylidene),
      which can be envisaged as a co-complex of IPr.ZnH2 and (HMDS)ZnH, is obtained
      when DMAB is employed, with the concomitant formation of heteroleptic
      bis(amido)borane [HB(NMe2)(HMDS)] and H2 evolution. NMR studies in d8-THF show
      that although the bulky carbene IPr does not bind to the zinc bis(amide), its
      presence in the reaction media is required in order to stabilise . Reactions
      using the slightly less sterically demanding NHC IXy (IXy = 1,3-bis-(2,6
      dimethylphenyl)imidazol-2-ylidene) led to the isolation and structural
      elucidation of the carbene adduct Zn(HMDS)2.IXy (). Contrastingly, mixtures of
      equimolar amounts of PhSiH3 and the zinc bis(amide) (60  degrees C, 3 h, hexane)
      afforded monomeric heteroleptic hydride (HMDS)ZnH.IPr (). NMR studies, including
      DOSY experiments, revealed that while the integrity of is retained in polar d8
      THF solutions, in lower polarity C6D6 it displays a much more complex solution
      behaviour, being in equilibrium with the homoleptic species ZnH2.IPr, Zn(HMDS)2
      and IPr. 

PMID- 25846581
TI  - A qualitative exploration of the impact of the economic recession in Spain on
      working, living and health conditions: reflections based on immigrant workers'
      experiences.
AB  - BACKGROUND: This study aimed to analyse how immigrant workers in Spain
      experienced changes in their working and employment conditions brought about
      Spain's economic recession and the impact of these changes on their living
      conditions and health status. METHOD: We conducted a grounded theory study. Data
      were obtained through six focus group discussions with immigrant workers (n = 44)
      from Colombia, Ecuador and Morocco, and two individual interviews with key
      informants from Romania living in Spain, selected by theoretical sample. RESULTS:
      Three categories related to the crisis emerged--previous labour experiences,
      employment consequences and individual consequences--that show how immigrant
      workers in Spain (i) understand the change in employment and working conditions
      conditioned by their experiences in the period prior to the crisis, and (ii)
      experienced the deterioration in their quality of life and health as consequences
      of the worsening of employment and working conditions during times of economic
      recession. CONCLUSION: The negative impact of the financial crisis on immigrant
      workers may increase their social vulnerability, potentially leading to the
      failure of their migratory project and a return to their home countries. Policy
      makers should take measures to minimize the negative impact of economic crisis on
      the occupational health of migrant workers in order to strengthen social
      protection and promote health and well-being.

PMID- 25846583
TI  - Postmenopausal hormone therapy-also use of estradiol plus levonorgestrel
      intrauterine system is associated with an increased risk of primary fallopian
      tube carcinoma.
AB  - Data on the possible impact of postmenopausal hormone therapy (HT) on the
      incidence of rare primary fallopian tube carcinoma (PFTC) are scarce. Therefore,
      we conducted a nationwide case-control study analyzing the association between
      the use of different HTs and PFTC. All women aged 50 years or older with an
      incident PFTC (n = 360) during 1995-2007 were identified from the Finnish Cancer
      Registry. For each case of PFTC, ten age- and place of residence-matched controls
      were selected from the Finnish National Population Register, which also provided
      information on parity. Data on HT purchases were received from the Prescription
      Register, and data on hysterectomies and sterilizations from the National Care
      Register. Controls with a salpingectomy before the PFTC diagnosis of the
      respective case were excluded. The PFTC risk in relation to different HTs was
      estimated with a conditional logistic regression model, adjusted for parity, age
      at last delivery, hysterectomy and sterilization. The use for five years or more
      of estradiol combined with levonorgestrel-releasing-intrauterine system (odds
      ratio 2.84, 95% confidence interval 1.10-7.38) and sequential estradiol-progestin
      therapy (EPT; 3.37; 2.23-5.08) were both linked with increases in the risk of
      PFTC, while the risk with use of estradiol-only therapy or continuous EPT was not
      statistically significantly increased. The OR for the use of tibolone for one
      year or more was 1.56 (0.55-4.41). The use of HT is related to an increased risk
      of PFTC, particularly when a progestin component is intrauterine or systemic
      progestin is given in sequential manner. 

PMID- 25846584
TI  - Pretreatment with lipopolysaccharide attenuates diethylnitrosamine-caused liver
      injury in mice via TLR4-dependent induction of Kupffer cell M2 polarization.
AB  - In this study, we found that pretreatment with low dose of lipopolysaccharide
      (LPS), also known as lipoglycans and endotoxin, obviously attenuated liver injury
      caused by diethylnitrosamine (DEN) in mice. This protective effect was described
      by decreased ALT, TNF-alpha, and IL-1beta and increased TGF-beta production.
      However, Toll-like receptor 4-deficient (TLR4(-/-)) or macrophages depletion
      abolished this protection in mice, which revealed Kupffer cells (KCs) and TLR4 to
      be crucial for the prevention of LPS against DEN-induced damage. Further study
      revealed that LPS pretreatment induced the KCs to M2 polarization and impaired
      the signaling of MAPKs and NF-kappaB that mediated the production of inflammatory
      cytokines. Moreover, T regulatory cells (Tregs) were also recruited to the liver,
      which may mediate immunosuppression and participate in the prevention of DEN
      induced injury. Our results suggested that LPS protected against DEN-induced
      hepatitis via induction of M2 Kupffer cells and recruitment of Tregs, which
      contributes to liver tolerance in TLR4-dependent mechanism.

PMID- 25846585
TI  - Single nucleotide polymorphisms in the FAM167A-BLK gene are associated with
      polymyositis/dermatomyositis in the Han Chinese population.
AB  - Idiopathic inflammatory myopathies (IIMs) are autoimmune diseases influenced by
      genetic background and environmental factors. Recently, FAM167A-BLK gene has been
      identified as a potential genetic susceptibility locus for dermatomyositis (DM)
      in patients of European and Japanese populations. Our aim here was to investigate
      the association between FAM167A-BLK polymorphisms and IIMs risk in Chinese Han.
      The FAM167A-BLK single nucleotide polymorphisms (SNPs) rs2736340, rs7812879,
      rs13277113, rs2618479, rs2254546 and rs2248932 were analyzed in polymyositis (PM)
      patients (n = 310), DM patients (n = 535) and 968 ethnically matched healthy
      controls, with the Sequenom MassArray system. Our present study demonstrated that
      strong allele association was observed in overall PM/DM and PM patients for
      rs2736340 (P c = 6.48 * 10(-3); P c = 0.013, respectively), rs7812879 (P c =
      0.017; P c = 0.034, respectively) and rs13277113 (P c = 0.011; P c = 0.047,
      respectively). These three SNPs were significantly associated with interstitial
      lung disease (ILD) in overall PM/DM patients (all, P c < 0.05). The frequency of
      the five haplotypes of the five SNPs (rs2736340, rs7812879, rs13277113, rs2618479
      and rs2254546) was also significantly different between overall PM/DM, PM or DM
      patients and healthy controls. This was the first study to demonstrate that the
      FAM167A-BLK polymorphisms were associated with Chinese PM/DM patients or these
      patients with ILD, indicating that PM/DM might share common gene with other
      autoimmune diseases.

PMID- 25846586
TI  - [Neuropathology of cerebral cortices in neurodegenerative disorders].
AB  - Clinical symptoms and signs are important keys to detect cortical lesions of
      neurological disorders. Each disease presents with characteristic cortical
      lesions and distributions of abnormal inclusions. In the cerebral cortices,
      neuronal and glial inclusions consist of abnormally aggregated proteins, such as
      tau or TDP-43, which are disease-specific. However, neurological disorders span
      across a wide spectrum and individual variations exist in within populations of
      the same disease. Therefore, knowledge about disease-specific pathologies may
      provide useful guidelines for differential diagnosis of cortical lesions
      occurring in neurological diseases. 

PMID- 25846587
TI  - [What matters more in the white matter: thinking inside of the brain].
AB  - The proportion of white matter in the brain has increased during evolution, and
      white matter comprises approximately half of the human brain. Its macroscopic as
      well as microscopic structures change during development, aging, and disease
      progression as well as following physical or mental training. Knowledge about the
      structural plasticity of the white matter may alter our cortex-oriented view of
      brain functions and expand our strategies for diagnosis and treatment, including
      rehabilitation, since the gray and white matter are complementary. Although the
      presence of white matter lesions is easy to detect with magnetic resonance
      imaging of the brain, their qualitative differentiation requires vast knowledge
      about the underlying processes. Examples from multiple ischemic lesions caused by
      different disease processes affecting the cerebral arteries are presented for
      comparison. It is worth considering "what matters more in the white matter" by
      taking into account the basic structures of the brain as well as their
      plasticity. Such "thinking inside of the brain" may further expand our
      understanding of the brain to improve our clinical interpretations and
      treatments. 

PMID- 25846588
TI  - [Current concepts regarding cortical dementia].
AB  - Dementia manifests during the presenile and senile periods in many diseases and
      pathological conditions. Alzheimer's disease (AD) and frontotemporal lobar
      degeneration (FTLD) are the two main diseases in which cortical dementia is
      observed. FTLD includes frontotemporal dementia (FTD), progressive non-fluent
      aphasia (PNFA), and semantic dementia (SD). Cortical dementia has also been
      described in posterior cortical atrophy (CPA) and primary progressive non-fluent
      or logopenic aphasia (PNFLA). This article describes and discusses historical
      changes in the disease concept; diagnostic characteristics, including pathology
      and imaging analysis; clinical symptoms based on local cognitive function in the
      cerebral cortex; and other recent topics on dementia. 

PMID- 25846589
TI  - [Subcortical ischemic vascular dementia: lesson from hereditary cerebral small
      vessel disease].
AB  - Subcortical ischemic vascular dementia (SIVD) is a main subgroup of vascular
      dementia related to cerebral small vessel disease. Risk factors for SIVD include
      hypertension, ageing, and diabetes mellitus, but the specific contribution of
      each factor to the development of cerebral small vessel disease remains obscure.
      This is mainly because SIVD in the elderly might be affected by many factors
      related to the ageing process. Hereditary cerebral small vessel diseases,
      including cerebral autosomal-dominant or autosomal recessive arteriopathy with
      subcortical infarcts and leukoencephalopathy (CADASIL or CARASIL) and cerebral
      amyloid angiopathy, are affected by different pathomechanisms, but these diseases
      indicate a clear a role of the cerebral small vessel on subcortical dementia.
      CADASIL is caused by a cysteine residue-related mutation in the EGF-like repeat
      on the extracellular domain of Notch3. Pathological examination of a CADASIL
      brain indicated abnormal accumulation of the extracellular domain of Notch3 with
      extracellular matrix proteins, including tissue inhibitor of metalloproteinase 3
      and vitronectin, around vascular smooth muscle cells. CARASIL is caused by a
      mutation in HTAR1, a serine protease that regulates transforming growth factor
      (TGF)-beta signaling. The mutation in HTAR1 related to CARASIL fails to repress
      TGF-beta signaling and induces the accumulation of extracellular matrix,
      including the extra domain-A region of fibronectin and versican. The individual
      and common pathomechanisms of hereditary cerebral small vessel disease are
      discussed in this review. 

PMID- 25846590
TI  - [Differential diagnosis of dementia with lewy bodies].
AB  - Kosaka and colleagues first reported dementia with Lewy bodies (DLB) in 1976.
      They have also established the concept of DLB. It is important to differentiate
      DLB from other dementia, especially Alzheimer disease (AD), because the medical
      treatment, management, and prognosis of DLB and AD are different. We have used
      several clinical features and imaging tools to differentiate between DLB and AD.
      With regard to clinical features, patients with DLB have relatively mild memory
      disturbances and fluctuating cognition. However, compared to patients with AD
      they have more severe disturbances of attention and executive, visuospatial
      functions, visual hallucination, depression, autonomic symptoms. In addition,
      they show the presence of REM sleep behavior disorder and idiopathic
      parkinsonism. On performing imaging analysis, patients with DLB showed milder
      atrophy in the medial temporal lobe on brain MRI, reduced occipital activity on
      SPECT or PET, reduced MIBG uptake on MIBG cardiac scintigraphy, and low dopamine
      transporter activity in the basal ganglia on SPECT or PET. 

PMID- 25846591
TI  - [White Matter Lesion and Alzheimer's Disease: The Association between Small
      Vessel Disease and Neuropsychiatric Symptoms in Alzheimer's Disease].
AB  - Cerebral small vessel disease (SVD), including subcortical lacunar infarcts
      (lacunes) and white matter hyperintensities (WMH), is commonly observed on MRI of
      elderly individuals with and without dementia. SVD is frequently observed in
      patients with Alzheimer's disease (AD). However, the association between SVD and
      clinical symptoms exhibited by patients with AD remains unclear. Our recent
      studies suggest that cerebral SVD observed on CT/MRI of patients with AD is
      associated with delusions and delirium as well as depression. Mechanisms
      underlying these psychiatric symptoms in patients with AD remain unclear. 

PMID- 25846592
TI  - [Understanding the neuropsychological symptoms associated with cortical
      dysfunction].
AB  - Damage to association cortices can result in a variety of cognitive and
      behavioral symptoms. Superficially, the relationship between lesion sites and the
      corresponding symptoms seems constant. However, some degree of dissociation of
      symptoms among patients with different etiologies appears to be the rule rather
      than the exception, even when the lesion locations appear similar in neuroimaging
      studies. Examinations of patients with primary progressive aphasia (PPA) have
      challenged the classic language model that is based on observations mainly made
      in patients with cerebrovascular diseases. The neuropsychological findings of
      patients with semantic variant PPA and neuroimaging evidence in healthy subjects
      converge to indicate that the anterior temporal lobe is an important component of
      language and semantic networks. Recent findings, however, have demonstrated that
      atrophy and dysfunction in patients with semantic variant PPA involve a number of
      regions in addition to the anterior temporal lobe. This indicated that
      specifically linking language deficits to the anterior temporal lobe is
      difficult. An understanding the pathophysiological processes is require to
      comprehend the symptoms of cortical dysfunction, especially in the association
      cortices. 

PMID- 25846593
TI  - [Investigating the symptoms of white matter disorders].
AB  - In this presentation, I will examine the intricate systemic connections in the
      white matter and the disturbances that occur due to diseases. In particular, I
      will discuss Marchiafava-Bignami disease, leukodystrophy with neuroaxonal
      spheroids, and myotonic dystrophy. Investigation of all three diseases reveals
      the crosstalk essential for the healthy brain and the resulting dysfunctions that
      follow lesions of different etiologies. 

PMID- 25846594
TI  - [Investigation of the Cerebral Cortex Using Magnetoencephalography(MEG)].
AB  - Cortical neurons are excited by signals from the thalamus that are conducted via
      thalamocortical fibers. As the cortex receives these signals, electric currents
      are conducted through the apical dendrites of pyramidal cells in the cerebral
      cortex. These electric currents generate magnetic fields. These electric and
      magnetic currents can be recorded by electroencephalography (EEG) and
      magnetoencephalography (MEG), respectively. The spatial resolution of MEG is
      higher than that of EEG because magnetic fields, unlike electric fields, are not
      affected by current conductivity. MEG also has several advantages over functional
      magnetic resonance imaging (fMRI). It (1) is completely non-invasive; (2)
      measures neuronal activity rather than blood flow or metabolic changes; (3) has a
      higher temporal resolution than fMRI on the order of milliseconds; (4) enables
      the measurement of stimulus-evoked and event-related responses; (5) enables the
      analysis of frequency (i.e., brain rhythm) response, which means that
      physiological changes can be analyzed spatiotemporally; and (6) enables the
      detailed analysis of results from an individual subject, which eliminates the
      need to average results over several subjects. This latter advantage of MEG
      therefore enables the analysis of inter-individual differences. 

PMID- 25846595
TI  - [Cerebral white matter lesions: differential diagnosis on magnetic resonance
      imaging].
AB  - It is often difficult to make a differential diagnosis of cerebral white-matter
      lesions on magnetic resonance images (MRI), because imaging findings are non
      specific. However, it is possible to make a correct diagnosis of some kinds of
      cerebral white-matter lesions upon a detailed analysis of MRI. In analyzing MRI
      of cerebral white matter lesions, the localization and shape of white-matter
      lesions are important factors to make a differential diagnosis. Other images such
      as diffusion-weighted or T2-star weighted images are sometimes also useful for
      making such a diagnosis. In this manuscript, I describe how to read MRI of
      cerebral white-matter lesions, and present some educational cases. 

PMID- 25846596
TI  - [White matter fiber tractography and quantitative analysis of diffusion tensor
      imaging].
AB  - Magnetic resonance diffusion tensor imaging (DTI) is a noninvasive technique that
      can identify and quantify white matter tracts by evaluating the diffusion of
      water in biological tissues. While association fibers are bundles of axons within
      the brain that unite different parts of the same cerebral hemisphere, projection
      fibers are bundles of axons that unite the cortex with lower parts of the brain
      and the spinal cord. The commissural fibers are axon bundles that connect the two
      hemispheres of the brain. Quantitative analysis of DTI can be roughly classified
      into three types: region of interest analysis, tract-specific analysis, and fully
      automated hypothesis free whole brain analysis. 

PMID- 25846597
TI  - [Volumetry of cerebral gray and white matter using VSRAD(r)].
AB  - Voxel-based morphometry (VBM) using structural brain MRI has been widely used for
      the early and differential diagnosis and evaluation of disease progression in
      neuropsychiatric diseases. VBM of MRI data comprises segmentation into gray
      matter, white matter, and cerebrospinal fluid partitions; anatomical
      standardization of all the images to the same stereotactic space using linear
      affine transformation and further non-linear warping and smoothing; and finally
      performing statistical analysis. Stand-alone VBM software using SPM8 plus DARTEL
      running on Windows (Voxel-based Specific Regional analysis system for Alzheimer's
      disease, VSRAD<sup>(r)</sup>) has been developed as an adjunct to the clinical
      assessment. This software provides a Z-score map as a result of the comparison of
      the patient's MRI with a normal database. 

PMID- 25846598
TI  - [Cortical gray matter lesions in multiple sclerosis].
AB  - Multiple sclerosis (MS) and neuromyelitis optica (NMO) are the two main
      autoimmune and inflammatory diseases of the central nervous system. MS is
      considered an 'oligodendrocytopathy' with undefined autoantibodies, whereas NMO
      is considered an 'astrocytopathy' with aquaporin-4 antibodies. Both have long
      been considered autoimmune diseases that primarily affect the white matter (WM).
      However, recent interest in gray matter (GM) pathology is emerging. Pathological
      evaluations reveal that substantial cortical demyelination is prominent at all
      stages or courses of MS. In addition, the neurodegeneration in MS is present not
      only in GM demyelination but also in normal-appearing GM. NMO involves cortical
      neurodegeneration and unique dynamics of astrocytes; however, no cortical
      demyelination is seen. Thus, MS and NMO are distinct diseases with unique
      pathological features in the brain WM and GM. Although the cause of GM and WM
      lesions in MS and NMO has not been fully determined, improved knowledge about the
      pathomechanisms in affected brains is desired. This would result in a more
      targeted pharmacotherapeutic approach to these diseases. 

PMID- 25846599
TI  - [Brain function and white matter].
AB  - Accumulated evidence shows that neural information processing takes place in
      superficial layers of the brain called the gray matter. Synapses, which connect
      different neurons reside in the gray matter and are considered the major
      components of information processing and plasticity. On the other hand,
      myelinated axons lie beneath the gray matter. These bundles of cables connect
      neurons in the different brain regions to form functional neural circuits.
      Myelinated axons were of little of interest to neuroscientists and have long been
      ignored in the formation of functional neuronal circuits. Recent evidence shows
      that myelin formed by oligodendrocytes shows plastic changes depending on
      neuronal activity. In this issue, we discuss the plastic changes of myelin and
      its functional role in learning and training. 

PMID- 25846600
TI  - [Criteria for the diagnosis of corticobasal degeneration].
AB  - Corticobasal degeneration (CBD) is a distinct neurodegenerative disorder
      characterized by widespread neuronal and glial accumulation of abnormally
      phosphorylated tau protein. Patients with CBD often present with corticobasal
      syndrome (CBS) showing impairment of the motor system, cognition, or both.
      Several studies demonstrate that they may also present with progressive
      supranuclear palsy syndrome (PSPS), aphasia, Alzheimer disease-like dementia, or
      behavioral changes, suggesting that CBS is merely one of the presenting
      phenotypes of CBD. Accurate diagnosis is important for future clinical trials
      using drugs aimed at modifying the underlying tau pathology. Although previous
      CBD diagnostic criteria reflected only CBS, Armstrong et al. proposed new
      diagnostic criteria for CBD in 2013 (Armstrong's criteria). The new criteria
      include 4 CBD phenotypes, including CBS, frontal behavioral-spatial syndrome
      (FBS), nonfluent/agrammatic variant of primary progressive aphasia (naPPA), and
      PSPS. These phenotypes were combined to create 2 sets of criteria: specific
      clinical research criteria for probable CBD (cr-CBD) and broader criteria for
      possible CBD that are more inclusive but have a higher probability of detecting
      other tau-based pathologies (p-CBD). However, two recent studies revealed that
      the sensitivity and specificity of these criteria were insufficient. Further
      refinement of the criteria is needed via biomarker research with prospective
      study designs. (Received August 19, 2014; Accepted December 26, 2014: Published
      April 1, 2015). 

PMID- 25846601
TI  - [Clinical and histological characteristics of ictal onset zone in cases of
      intractable epilepsy associated with dysembryoplastic neuroepithelial tumor].
AB  - Although the epileptogenic location of dysembryoplastic neuroepithelial tumors
      (DNTs) is controversial, it has recently been thought to be located within
      cortical dysplasia (CD) due to its frequent association with CD. Among the 84
      resection surgeries for intractable epilepsy performed in our institution between
      January 2003 and April 2010, three patients had epileptogenic DNTs. In two cases,
      chronic subdural electrocorticography (ECoG) was performed, and the ictal onset
      zone was revealed to be in the cortex around the DNT. The ictal onset zone was
      resected along with the DNT, and good seizure outcome was achieved. Although
      histological examination of the ictal onset zone revealed mild gliosis,
      coexistence of CD was not noted. In the third case, the DNT was located in the
      left lateral temporal lobe and the intraoperative ECoG revealed frequent
      paroxysmal activity in the medial temporal lobe. Resection of the lateral
      temporal lobe involving the tumor did not result in good seizure control. The
      optimal surgical treatment of DNT is controversial. Some authors consider
      lesionectomy to be sufficient for good seizure control, whereas others advocate
      that additional resection of the epileptogenic zone beside the tumor improves
      outcome. Because the epileptogenic location of DNT varies among cases, it is
      important to identify its location by preoperative multimodal examinations,
      including chronic subdural ECoG recordings.

PMID- 25846603
TI  - Editorial: Diet and children's behaviour problems--disentangling urban myth from
      clinical reality.

PMID- 25846602
TI  - Pharmacists' knowledge about use of topical corticosteroids in atopic dermatitis:
      Pre and post continuing professional development education.
AB  - BACKGROUND/OBJECTIVES: Topical corticosteroids (TCS) are the standard of care in
      paediatric atopic dermatitis (pAD). Parents commonly cite TCS phobia as a major
      impediment to treatment adherence. Misinformation on TCS side-effects can impact
      on perceptions of TCS safety. We aimed to assess pharmacists' beliefs and
      information on the safety of TCS in pAD treatment and determine whether their
      beliefs could be modified. METHODS: Australian pharmacists attending a continuing
      professional development conference were assessed before and after an evidence
      based lecture on the use of TCS in pAD. Responses were recorded in real time on
      electronic keypads. RESULTS: The mean response rate was 86% of the 292 surveyed.
      Of responders, 64% recognised that treatment non-adherence was a major reason for
      treatment failure in pAD. The post-education session assessment demonstrated a
      major attitude shift compared to the pre-education assessment. After education,
      pharmacists would instruct parents/patients to apply TCS until the eczema is
      clear (27 vs 92% pre and post-education, P < 0.0001). The proportion that would
      instruct patients to use TCS sparingly dropped from 54 to 8% (P < 0.0001). The
      belief that cutaneous atrophy was the commonest side-effect dropped from 46 to 7%
      (P < 0.0001). The belief that side-effects from TCS would occur, even if used
      appropriately, dropped from 56 to 11% post-education (P < 0.0001). CONCLUSIONS:
      The significant knowledge gaps about the use and safety of TCS in pAD in
      Australian pharmacists and their advice to patients potentially contributes to
      poor treatment concordance. These attitudes appear modifiable through targeted,
      evidence-based education delivered by a dermatologist.

PMID- 25846604
TI  - Mesenchymal stem cell application in children with subacute sclerosing
      panencephalitis.
AB  - Subacute sclerosing panencephalitis (SSPE) is a serious, often fatal disease that
      responds poorly to current treatment modalities. Recently, the ability of
      mesenchymal stem cells (MSCs) to produce neurotrophic factors and inflammatory
      molecules has placed them among potential treatment agents for neurological
      conditions. We report the results of four patients treated with MSC for SSPE. The
      patients were followed up clinically, and by periodical laboratory evaluations,
      magnetic resonance imaging (MRI), and electroencephalography. One patient
      deteriorated to stage III of the disease, two patients remained in the same
      stage, and one died from disease progression and respiratory problems.
      Neurological findings and electroencephalography scores were consistent with the
      clinical course of the patient whereas MRI showed new inflammatory lesions in two
      patients. This is the first report of the application of MSC in SSPE. No benefit
      is demonstrated. 

PMID- 25846605
TI  - Gene expression of cultured human chondrocytes as a model for assessing
      neutralization efficacy of soluble TNFalpha by TNFalpha antagonists.
AB  - Tumor necrosis factor-alpha (TNFalpha) antagonists are efficacious in the
      treatment of various immune-mediated inflammatory diseases. Because of rapidly
      growing demand for developing new or biosimilar versions of these biologicals,
      the need to create in vitro testing models that best represent physiological
      conditions is increasing. Primary human chondrocytes were used for potency
      evaluation and comparison between the molecular effects of anti-TNFalpha
      biologicals. Infliximab and etanercept were chosen to assess the suitability of
      chondrocyte cell culture for determination of anti-TNFalpha neutralization
      efficacy employing quantitative reverse transcription-polymerase chain reaction
      (qRT-PCR) technology. Use of both anti-TNFalpha biologics resulted in decrease of
      TNFalpha-stimulated expression of various matrix metalloproteinases, interleukins
      and other inflammation-related genes in our cell model. Significant differences
      in inhibition efficacy of etanercept and infliximab were observed, which were
      confirmed also on protein level. To evaluate the potency of anti-TNFalpha
      biologicals, a selection of TNFalpha-responsive target genes was made from the
      gene array data. The selected genes were employed in development of statistical
      model, which enables comparability of anti-TNFalpha biologicals. The presented
      analytical approach is suitable for assessment of the neutralization efficacy of
      various anti-TNFalpha biologicals. As such, it can be used for additional
      comprehensive characterization and comparability of TNF antagonists in
      preclinical drug testing. 

PMID- 25846606
TI  - Residential radon and birth defects: A population-based assessment.
AB  - BACKGROUND: Associations have been reported between maternal radiation exposure
      and birth defects. No such studies were found on radon. Our objective was to
      determine if there is an association between living in areas with higher radon
      levels and birth defects. METHODS: The Texas Birth Defects Registry provided data
      on all birth defects from 1999 to 2009 from the entire state. Mean radon levels
      by geologic region came from the Texas Indoor Radon Survey. The association
      between radon and birth defects was estimated using multilevel mixed effect
      Poisson regression. RESULTS: Birth defects overall were not associated with
      residential radon levels. Of the 100 other birth defect groups with at least 500
      cases, 14 were significantly elevated in areas with high mean radon level in
      crude analyses, and 9 after adjustment for confounders. Cleft lip with/without
      cleft palate had an adjusted prevalence ratio of 1.16 per 1 picoCurie/liter
      (pCi/L) increase in exposure to region mean radon, 95% confidence interval, 1.08
      1.26. Cystic hygroma / lymphangioma had an adjusted prevalence ratio of 1.22 per
      1 pCi/L increase, 95% confidence interval, 1.02-1.46. Other associations were
      suggested but not as consistent: three skeletal defects, Down syndrome, other
      specified anomalies of the brain, and other specified anomalies of the bladder
      and urethra. CONCLUSION: In the first study of residential radon and birth
      defects, we found associations with cleft lip w/wo cleft palate and cystic
      hygroma / lymphangioma. Other associations were suggested. The ecological nature
      of this study and multiple comparisons suggest that our results be interpreted
      with caution.

PMID- 25846607
TI  - Inhibition of autophagy using 3-methyladenine increases cisplatin-induced
      apoptosis by increasing endoplasmic reticulum stress in U251 human glioma cells.
AB  - Cisplatin is one of the most widely used chemotherapeutic drugs; however, the
      side effects and drug resistance limit its usage. Previous findings have
      demonstrated that cisplatin kills tumor cells through endoplasmic reticulum (ER)
      stress, which provides a novel method to minimize cisplatin toxicity and
      circumvent cisplatin resistance. ER stress induces cell autophagy, cell apoptosis
      and the complicated regulatory network between them. The role of autophagy in
      cisplatin chemotherapy remains to be elucidated. 3-Methyladenine (3-MA) is
      normally used as an inhibitor of autophagy. The present study reveals a
      significant role of the inhibition of autophagy by treatment with 3-MA and
      cisplatin in combination in U251 human glioma cells. It was demonstrated that
      cisplatin induced the ER stress associated with apoptosis and autophagy in U251
      cells. Inhibition of autophagy by 3-MA increased the expression levels of protein
      disulfide isomerase, ubiquitinated proteins, glucose regulated protein 78 and
      CCAAT-enhancer-binding protein homologous protein, and induced the activation of
      caspase-4 and caspase-3. Treatment with 3-MA combined with cisplatin increased
      cisplatin-induced apoptosis by increasing ER stress. Therefore, the inhibition of
      autophagy has the potential to improve cisplatin chemotherapy.

PMID- 25846609
TI  - Mechanistic studies of malonic acid-mediated in situ acylation.
AB  - We have previously introduced an easy to perform, cost-effective and highly
      efficient acetylation technique for solid phase synthesis (SPPS). Malonic acid is
      used as a precursor and the reaction proceeds via a reactive ketene that
      acetylates the target amine. Here we present a detailed mechanistic study of the
      malonic acid-mediated acylation. The influence of reaction conditions, peptide
      sequence and reagents was systematically studied. Our results show that the
      methodology can be successfully applied to different types of peptides and
      nonpeptidic molecules irrespective of their structure, sequence, or conformation.
      Using alkyl, phenyl, and benzyl malonic acid, we synthesized various acyl
      peptides with almost quantitative yields. The ketenes obtained from the different
      malonic acid derived precursors were characterized by in situ (1) H-NMR. The
      reaction proceeded in short reaction times and resulted in excellent yields when
      using uronium-based coupling agents, DIPEA as a base, DMF/DMSO/NMP as solvents,
      Rink amide/Wang/Merrifield resins, temperature of 20 degrees C, pH 8-12 and 5 min
      preactivation at inert atmosphere. The reaction was unaffected by Lewis acids,
      transition metal ions, surfactants, or salt. DFT studies support the kinetically
      favorable concerted mechanism for CO2 and ketene formation that leads to the
      thermodynamically stable acylated products. We conclude that the malonic acid
      mediated acylation is a general method applicable to various target molecules.

PMID- 25846610
TI  - Enhanced ultrasonography using a nano/microbubble contrast agent for islet
      transplantation.
AB  - Recent basic and clinical studies have assessed the use of highly sensitive
      imaging modalities for visualizing transplanted islets. We investigated the
      utility of enhanced ultrasonography, combined with fluorescent acoustic liposome
      nano/microbubbles (FALs), for evaluating angiogenesis and the endocrine function
      of transplanted islets. BALB/c mice were classified into three groups: Diabetic
      mice that underwent syngeneic islet transplantation into the subrenal capsule and
      achieved normoglycemia (Tx group); those that failed to achieve normoglycemia (Tx
      DM group); and those not receiving any treatment (DM group). Mice were examined
      by FAL-enhanced high frequency ultrasonography. The echogenicity of the islets
      increased rapidly within the first minute after injection of FALs and remained at
      a higher level in the Tx group, while small increases were observed in the other
      two groups. In histological assessments, fluorescently stained erythrocytes could
      be seen in and around the transplanted islets, indicating that the transplanted
      islets were enhanced by infusion of FALs via vessel networks between the
      engrafted islets and tissue. Furthermore, the echogenicity correlated
      significantly with endocrine parameters, including blood glucose (BG), serum
      insulin, and the BG change in the glucose tolerance test. In conclusion, the
      echogenicity of the islets under FAS-enhanced ultrasonosonography correlated with
      the endocrine status of transplanted islets. 

PMID- 25846608
TI  - Alstrom Syndrome: Mutation Spectrum of ALMS1.
AB  - Alstrom Syndrome (ALMS), a recessive, monogenic ciliopathy caused by mutations in
      ALMS1, is typically characterized by multisystem involvement including early cone
      rod retinal dystrophy and blindness, hearing loss, childhood obesity, type 2
      diabetes mellitus, cardiomyopathy, fibrosis, and multiple organ failure. The
      precise function of ALMS1 remains elusive, but roles in endosomal and ciliary
      transport and cell cycle regulation have been shown. The aim of our study was to
      further define the spectrum of ALMS1 mutations in patients with clinical features
      of ALMS. Mutational analysis in a world-wide cohort of 204 families identified
      109 novel mutations, extending the number of known ALMS1 mutations to 239 and
      highlighting the allelic heterogeneity of this disorder. This study represents
      the most comprehensive mutation analysis in patients with ALMS, identifying the
      largest number of novel mutations in a single study worldwide. Here, we also
      provide an overview of all ALMS1 mutations identified to date. 

PMID- 25846611
TI  - Emerging concepts of pain therapy based on neuronal mechanisms.
AB  - Current pain treatment is successful in many patients, but nevertheless numerous
      problems have to be solved because still about 20% of the people in the
      population suffer from chronic pain. A major aim of pain research is, therefore,
      to clarify the neuronal mechanisms which are involved in the generation and
      maintenance of different pain states and to identify the mechanisms which can be
      targeted for pain treatment. This volume on pain control addresses neuronal pain
      mechanisms at the peripheral, spinal, and supraspinal level which are thought to
      significantly contribute to pain and which may be the basis for the development
      of new treatment principles. This introductory chapter addresses the types of
      pain which are currently defined based on the etiopathologic considerations,
      namely physiologic nociceptive pain, pathophysiologic nociceptive pain, and
      neuropathic pain. It briefly describes the structures and neurons of the
      nociceptive system, and it addresses molecular mechanisms of nociception which
      may become targets for pharmaceutical intervention. It will provide a frame for
      the chapters which address a number of important topics. Such topics are the
      concept of hyperalgesic priming, the role of voltage-gated sodium channels and
      nerve growth factor (NGF) in different inflammatory and neuropathic pain states,
      the hyperalgesic effects of NGF in different tissues, the contribution of
      proteinase-activated receptors (PARs) to the development of pain in several
      chronic pain conditions, the role of spinal NO and of glial cell activation in
      the generation and maintenance of inflammatory and neuropathic pain, the
      potential role of spinal inhibitory interneurons, the endogenous endocannabinoid
      system, and the importance of nonneuronal immune mechanisms in opioid signaling
      in the control of pain, the influence of spinal mechanisms on the expression of
      peripheral inflammation, the role of the amygdala and their connections to the
      medial prefrontal cortex in pain states, the experimental methods to test central
      sensitization of the nociceptive system in humans, and differences and
      similarities of the neuronal systems of pain and itch. Finally it will be
      discussed that both the concentration on single key molecules of nociception and
      the interference with disease-related mediators may provide novel approaches of
      pain treatment.

PMID- 25846613
TI  - Sodium channels and pain.
AB  - Human and mouse genetic studies have led to significant advances in our
      understanding of the role of voltage-gated sodium channels in pain pathways. In
      this chapter, we focus on Nav1.7, Nav1.8, Nav1.9 and Nav1.3 and describe the
      insights gained from the detailed analyses of global and conditional transgenic
      Nav knockout mice in terms of pain behaviour. The spectrum of human disorders
      caused by mutations in these channels is also outlined, concluding with a summary
      of recent progress in the development of selective Nav1.7 inhibitors for the
      treatment of pain. 

PMID- 25846614
TI  - Role of nerve growth factor in pain.
AB  - Nerve growth factor (NGF) was first identified as a substance that is essential
      for the development of nociceptive primary neurons and later found to have a role
      in inflammatory hyperalgesia in adults. Involvement of NGF in conditions with no
      apparent inflammatory signs has also been demonstrated. In this review we look at
      the hyperalgesic effects of exogenously injected NGF into different tissues, both
      human and animal, with special emphasis on the time course of these effects. The
      roles of NGF in inflammatory and neuropathic conditions as well as cancer pain
      are then reviewed. The role of NGF in delayed onset muscle soreness is described
      in more detail than its other roles based on the authors' recent observations.
      Acute effects are considered to be peripherally mediated, and accordingly,
      sensitization of nociceptors by NGF to heat and mechanical stimulation has been
      reported. Changes in the conductive properties of axons have also been reported.
      The intracellular mechanisms so far proposed for heat sensitization are direct
      phosphorylation and membrane trafficking of TRPV1 by TrkA. Little investigation
      has been done on the mechanism of mechanical sensitization, and it is still
      unclear whether mechanisms similar to those for heat sensitization work in
      mechanical sensitization. Long-lasting sensitizing effects are mediated both by
      changed expression of neuropeptides and ion channels (Na channels, ASIC, TRPV1)
      in primary afferents and by spinal NMDA receptors. Therapeutic perspectives are
      briefly discussed at the end of the chapter. 

PMID- 25846612
TI  - The pharmacology of nociceptor priming.
AB  - Nociceptors and neurons in the central nervous system (CNS) that receive
      nociceptive input show remarkable plasticity in response to injury. This
      plasticity is thought to underlie the development of chronic pain states. Hence,
      further understanding of the molecular mechanisms driving and maintaining this
      plasticity has the potential to lead to novel therapeutic approaches for the
      treatment of chronic pain states. An important concept in pain plasticity is the
      presence and persistence of "hyperalgesic priming." This priming arises from an
      initial injury and results in a remarkable susceptibility to normally
      subthreshold noxious inputs causing a prolonged pain state in primed animals.
      Here we describe our current understanding of how this priming is manifested
      through changes in signaling in the primary nociceptor as well as through memory
      like alterations at CNS synapses. Moreover, we discuss how commonly utilized
      analgesics, such as opioids, enhance priming therefore potentially contributing
      to the development of persistent pain states. Finally we highlight where these
      priming models draw parallels to common human chronic pain conditions.
      Collectively, these advances in our understanding of pain plasticity reveal a
      variety of targets for therapeutic intervention with the potential to reverse
      rather than palliate chronic pain states. 

PMID- 25846615
TI  - Central sensitization in humans: assessment and pharmacology.
AB  - It is evident that chronic pain can modify the excitability of central nervous
      system which imposes a specific challenge for the management and for the
      development of new analgesics. The central manifestations can be difficult to
      quantify using standard clinical examination procedures, but quantitative sensory
      testing (QST) may help to quantify the degree and extend of the central
      reorganization and effect of pharmacological interventions. Furthermore, QST may
      help in optimizing the development programs for new drugs.Specific translational
      mechanistic QST tools have been developed to quantify different aspects of
      central sensitization in pain patients such as threshold ratios, provoked
      hyperalgesia/allodynia, temporal summation (wind-up like pain), after sensation,
      spatial summation, reflex receptive fields, descending pain modulation, offset
      analgesia, and referred pain areas. As most of the drug development programs in
      the area of pain management have not been very successful, the pharmaceutical
      industry has started to utilize the complementary knowledge obtained from QST
      profiling. Linking patients QST profile with drug efficacy profile may provide
      the fundamentals for developing individualized, targeted pain management programs
      in the future. Linking QST-assessed pain mechanisms with treatment outcome
      provides new valuable information in drug development and for optimizing the
      management regimes for chronic pain. 

PMID- 25846616
TI  - Nitric oxide-mediated pain processing in the spinal cord.
AB  - A large body of evidence indicates that nitric oxide (NO) plays an important role
      in the processing of persistent inflammatory and neuropathic pain in the spinal
      cord. Several animal studies revealed that inhibition or knockout of NO synthesis
      ameliorates persistent pain. However, spinal delivery of NO donors caused dual
      pronociceptive and antinociceptive effects, pointing to multiple downstream
      signaling mechanisms of NO. This review summarizes the localization and function
      of NO-dependent signaling mechanisms in the spinal cord, taking account of the
      recent progress made in this field. 

PMID- 25846617
TI  - The role of the endocannabinoid system in pain.
AB  - Preparations of the Cannabis sativa plant have been used to analgesic effect for
      millenia, but only in recent decades has the endogenous system responsible for
      these effects been described. The endocannabinoid (EC) system is now known to be
      one of the key endogenous systems regulating pain sensation, with modulatory
      actions at all stages of pain processing pathways. The EC system is composed of
      two main cannabinoid receptors (CB1 and CB2) and two main classes of endogenous
      ligands or endocannabinoids (ECs). The receptors have distinct expression
      profiles, with CB1 receptors found at presynaptic sites throughout the peripheral
      and central nervous systems (PNS and CNS, respectively), whilst CB2 receptor is
      found principally (but not exclusively) on immune cells. The endocannabinoid
      ligands are lipid neurotransmitters belonging to either the N-acyl ethanolamine
      (NAEs) class, e.g. anandamide (AEA), or the monoacylglycerol class, e.g. 2
      arachidonoyl glycerol (2-AG). Both classes are short-acting transmitter
      substances, being synthesised on demand and with signalling rapidly terminated by
      specific enzymes. ECs acting at CB1 negatively regulate neurotransmission
      throughout the nervous system, whilst those acting at CB2 regulate the activity
      of CNS immune cells. Signalling through both of these receptor subtypes has a
      role in normal nociceptive processing and also in the development resolution of
      acute pain states. In this chapter, we describe the general features of the EC
      system as related to pain and nociception and discuss the wealth of preclinical
      and clinical data involving targeting the EC system with focus on two areas of
      particular promise: modulation of 2-AG signalling via specific enzyme inhibitors
      and the role of spinal CB2 in chronic pain states. 

PMID- 25846618
TI  - The role of glia in the spinal cord in neuropathic and inflammatory pain.
AB  - Chronic pain, both inflammatory and neuropathic, is a debilitating condition in
      which the pain experience persists after the painful stimulus has resolved. The
      efficacy of current treatment strategies using opioids, NSAIDS and
      anticonvulsants is limited by the extensive side effects observed in patients,
      underlining the necessity for novel therapeutic targets. Preclinical models of
      chronic pain have recently provided evidence for a critical role played by glial
      cells in the mechanisms underlying the chronicity of pain, both at the site of
      damage in the periphery and in the dorsal horn of the spinal cord. Here microglia
      and astrocytes respond to the increased input from the periphery and change
      morphology, increase in number and release pro-nociceptive mediators such as ATP,
      cytokines and chemokines. These gliotransmitters can sensitise neurons by
      activation of their cognate receptors thereby contributing to central
      sensitization which is fundamental for the generation of allodynia, hyperalgesia
      and spontaneous pain. 

PMID- 25846619
TI  - Plasticity of inhibition in the spinal cord.
AB  - Inhibitory interneurons, which use GABA and/or glycine as their principal
      transmitter, have numerous roles in regulating the transmission of sensory
      information through the spinal dorsal horn. These roles are likely to be
      performed by different populations of interneurons, each with specific locations
      in the synaptic circuitry of the region. Peripheral nerve injury frequently leads
      to neuropathic pain, and it is thought that loss of function of inhibitory
      interneurons in the dorsal horn contributes to this condition. Several mechanisms
      have been proposed for this disinhibition, including death of inhibitory
      interneurons, decreased transmitter release, diminished activity of these cells
      and reduced effectiveness of GABA and glycine as inhibitory transmitters.
      However, despite numerous studies on this important topic, it is still not clear
      which (if any) of these mechanisms contributes to neuropathic pain after nerve
      injury. 

PMID- 25846620
TI  - Modulation of peripheral inflammation by the spinal cord.
AB  - The central nervous system, and the spinal cord in particular, is involved in
      multiple mechanisms that influence peripheral inflammation. Both pro- and anti
      inflammatory feedback loops can involve just the peripheral nerves and spinal
      cord or can also include more complex, supraspinal structures such as the vagal
      nuclei and the hypothalamic-pituitary axis. Analysis is complicated by the fact
      that inflammation encompasses a constellation of end points from simple edema to
      changes in immune cell infiltration and pathology. Whether or not any of these
      individual elements is altered by any potential mechanism is determined by a
      complex algorithm including, but not limited to, chronicity of the inflammation,
      tissue type, instigating stimulus, and state/tone of the immune system.
      Accordingly, the pharmacology and anatomical substrate of spinal cord modulation
      of peripheral inflammation are discussed with regard to peripheral tissue type,
      inflammatory insult (initiating stimulus), and duration of the inflammation. 

PMID- 25846621
TI  - The relationship between opioids and immune signalling in the spinal cord.
AB  - Opioids are considered the gold standard for the treatment of moderate to severe
      pain. However, heterogeneity in analgesic efficacy, poor potency and side effects
      are associated with opioid use, resulting in dose limitations and suboptimal pain
      management. Traditionally thought to exhibit their analgesic actions via the
      activation of the neuronal G-protein-coupled opioid receptors, it is now widely
      accepted that neuronal activity of opioids cannot fully explain the initiation
      and maintenance of opioid tolerance, hyperalgesia and allodynia. In this review
      we will highlight the evidence supporting the role of non-neuronal mechanisms in
      opioid signalling, paying particular attention to the relationship of opioids and
      immune signalling. 

PMID- 25846622
TI  - The role of proteases in pain.
AB  - Proteinase-activated receptors (PARs) are a family of G protein-coupled receptor
      that are activated by extracellular cleavage of the receptor in the N-terminal
      domain. This slicing of the receptor exposes a tethered ligand which binds to a
      specific docking point on the receptor surface to initiate intracellular
      signalling. PARs are expressed by numerous tissues in the body, and they are
      involved in various physiological and pathological processes such as food
      digestion, tissue remodelling and blood coagulation. This chapter will summarise
      how serine proteinases activate PARs leading to the development of pain in
      several chronic pain conditions. The potential of PARs as a drug target for pain
      relief is also discussed. 

PMID- 25846624
TI  - Itch and pain differences and commonalities.
AB  - Pain and itch are generally regarded antagonistic as painful stimuli such as
      scratching suppresses itch. Moreover, inhibition of pain processing by opioids
      generates itch further supporting their opposing role. Separate specific pathways
      for itch and pain processing have been uncovered, and several molecular markers
      have been established in mice that identify neurons involved in the processing of
      histaminergic and non-histaminergic itch on primary afferent and spinal level.
      These results are in agreement with the specificity theory for itch and might
      suggest that pain and itch should be investigated separately on the level of
      neurons, mediators, and mechanisms. However, in addition to broadly overlapping
      mediators of itch and pain, there is also evidence for overlapping functions in
      primary afferents: nociceptive primary afferents can provoke itch when activated
      very locally in the epidermis, and sensitization of both nociceptors and
      pruriceptors has been found following local nerve growth factor application in
      volunteers. Thus, also mechanisms that underlie the development of chronic itch
      and pain including spontaneous activity and sensitization of primary afferents as
      well as spinal cord sensitization may well overlap to a great extent. Rather than
      separating itch and pain, research concepts should therefore address the common
      mechanisms. Such an approach appears most appropriate for clinical conditions of
      neuropathic itch and pain and also chronic inflammatory conditions. While itch
      researchers can benefit from the large body of information of the pain field,
      pain researchers will find behavioral readouts of spontaneous itch much simpler
      than those for spontaneous pain in animals and the skin as source of the pruritic
      activity much more accessible even in patients. 

PMID- 25846625
TI  - Organoborane catalyzed regioselective 1,4-hydroboration of pyridines.
AB  - A bulky organoborane Ar(F)2BMe (Ar(F) = 2,4,6-tris(trifluoromethyl)phenyl, 1) has
      been synthesized. In C6D6 solution this organoborane and pyridine form a
      frustrated Lewis pair. Under mild conditions, 1 can efficiently catalyze 1,4
      hydroboration of a series of pyridines. This reaction is highly chemo- and
      regioselective. The reaction intermediate, a boronium complex
      [Py2Bpin][Ar(F)2B(H)Me] (3), was characterized in solution by NMR spectroscopy,
      which was also confirmed by DFT calculation. 

PMID- 25846623
TI  - Amygdala pain mechanisms.
AB  - A limbic brain area, the amygdala plays a key role in emotional responses and
      affective states and disorders such as learned fear, anxiety, and depression. The
      amygdala has also emerged as an important brain center for the emotional
      affective dimension of pain and for pain modulation. Hyperactivity in the
      laterocapsular division of the central nucleus of the amygdala (CeLC, also termed
      the "nociceptive amygdala") accounts for pain-related emotional responses and
      anxiety-like behavior. Abnormally enhanced output from the CeLC is the
      consequence of an imbalance between excitatory and inhibitory mechanisms.
      Impaired inhibitory control mediated by a cluster of GABAergic interneurons in
      the intercalated cell masses (ITC) allows the development of glutamate- and
      neuropeptide-driven synaptic plasticity of excitatory inputs from the brainstem
      (parabrachial area) and from the lateral-basolateral amygdala network (LA-BLA,
      site of integration of polymodal sensory information). BLA hyperactivity also
      generates abnormally enhanced feedforward inhibition of principal cells in the
      medial prefrontal cortex (mPFC), a limbic cortical area that is strongly
      interconnected with the amygdala. Pain-related mPFC deactivation results in
      cognitive deficits and failure to engage cortically driven ITC-mediated
      inhibitory control of amygdala processing. Impaired cortical control allows the
      uncontrolled persistence of amygdala pain mechanisms. 

PMID- 25846626
TI  - Toxic effects of cadmium on flatworm stem cell dynamics: A transcriptomic and
      ultrastructural elucidation of underlying mechanisms.
AB  - Stem cells or undifferentiated cells can cope more easily with external stresses.
      To evaluate the impact of toxic compounds on stem cell dynamics in vivo, in
      relation to other biological responses, we use the carcinogenic element cadmium
      and the regenerating model organism Macrostomum lignano. Through both BrdU and
      anti-histone H3 immunostainings, cadmium-induced effects were investigated at
      different stages of the stem cell cycle. A 24-h exposure to 100 and 250 MUM CdCl2
      significantly decreased the number of stem cells (neoblasts) in mitosis, whereas
      the number of cells in the S phase remained unchanged. After this short-term
      exposure, the ultrastructure of the neoblasts was minimally affected in contrast
      to the epidermal tissues. These results were supported by gene expression data:
      transcripts of cdc2 and pig3 were significantly upregulated during all
      treatments. Both genes are involved in the cell cycle progression and are
      transcribed in the gonadal region, where stem cells are highly represented. Based
      on a substantial increase in gene expression of heat shock proteins (HSP) and
      their high activity in the gonadal region, we hypothesize that these proteins are
      key players in the protection of stem cells against external stresses. Apart from
      the strong HSP induction, other protective processes including cell division,
      apoptosis and anti-oxidative defence, were also activated. We, therefore,
      conclude that the protection of stem cells against external stressors may be
      based on the interplay between stem cell maintenance, i.e. repair and recovery
      through division, on one hand and apoptosis on the other hand. (c) 2015 Wiley
      Periodicals, Inc. Environ Toxicol 31: 1217-1228, 2016. 

PMID- 25846627
TI  - Improved energy bound accuracy enhances the efficiency of continuous protein
      design.
AB  - Flexibility and dynamics are important for protein function and a protein's
      ability to accommodate amino acid substitutions. However, when computational
      protein design algorithms search over protein structures, the allowed flexibility
      is often reduced to a relatively small set of discrete side-chain and backbone
      conformations. While simplifications in scoring functions and protein flexibility
      are currently necessary to computationally search the vast protein sequence and
      conformational space, a rigid representation of a protein causes the search to
      become brittle and miss low-energy structures. Continuous rotamers more closely
      represent the allowed movement of a side chain within its torsional well and have
      been successfully incorporated into the protein design framework to design
      biomedically relevant protein systems. The use of continuous rotamers in protein
      design enables algorithms to search a larger conformational space than previously
      possible, but adds additional complexity to the design search. To design large,
      complex systems with continuous rotamers, new algorithms are needed to increase
      the efficiency of the search. We present two methods, PartCR and HOT, that
      greatly increase the speed and efficiency of protein design with continuous
      rotamers. These methods specifically target the large errors in energetic terms
      that are used to bound pairwise energies during the design search. By tightening
      the energy bounds, additional pruning of the conformation space can be achieved,
      and the number of conformations that must be enumerated to find the global
      minimum energy conformation is greatly reduced.

PMID- 25846628
TI  - Amino acid-based surfactants - do they deserve more attention?
AB  - The 20 standard amino acids (together with a few more that are not used in the
      biosynthesis of proteins) constitute a versatile tool box for synthesis of
      surfactants. Anionic, cationic and zwitterionic amphiphiles can be prepared and
      surfactants with several functional groups can be obtained by the proper choice
      of starting amino acid. This review gives examples of procedures used for
      preparation and discusses important physicochemical properties of the amphiphiles
      and how these can be taken advantage of for various applications. Micelles with a
      chiral surface can be obtained by self-assembly of enantiomerically pure
      surfactants and such supramolecular chirality can be utilized for asymmetric
      organic synthesis and for preparation of mesoporous materials with chiral pores.
      Surfactants based on amino acids with two carboxyl groups are effective chelating
      agents and can be used as collectors in mineral ore flotation. A surfactant based
      on cysteine readily oxidizes into the corresponding cystine compound, which can
      be regarded as a gemini surfactant. The facile and reversible cysteine-cystine
      transformation has been taken advantage of in the design of a switchable
      surfactant. A very attractive aspect of surfactants based on amino acids is that
      the polar head-group is entirely natural and that the linkage to the hydrophobic
      tail, which is often an ester or an amide bond, is easily cleaved. The rate of
      degradation can be tailored by the structure of the amphiphile. The ester linkage
      in betaine ester surfactants is particularly susceptible to alkaline hydrolysis
      and this surfactant type can be used as a biocide with short-lived action. This
      paper is not intended as a full review on the topic. Instead it highlights
      concepts that are unique to amino acid-based surfactants and that we believe can
      have practical implications. 

PMID- 25846629
TI  - Development of a nurse-assisted preanesthesia evaluation program for pediatric
      outpatient anesthesia.
AB  - BACKGROUND: Historically, anesthesiologists have conducted preanesthesia
      evaluation, but more recently, nurse practitioners (NPs) are increasingly
      assisting with the preanesthesia evaluation of children. In the current economic
      environment for healthcare, strategies to provide superior outcomes and
      exceptional patient experience at the lowest possible cost are constantly being
      explored. We examined whether well trained nurses, working alongside NPs, could
      safely and effectively assist in preanesthesia evaluation. The aim of this
      quality improvement project was to implement a new model for preanesthesia
      evaluation for healthy outpatient pediatric patients: nurse-assisted
      preanesthesia evaluation (NAPE). METHODS: Using quality improvement methods, Key
      Driver Diagrams and SMART aims gave direction for the training and clinical
      implementation of this new process. Using small tests of change and Plan-Do-Study
      Act cycles, we developed a training process and a stepwise process to integrate
      them into the clinical work flow. The primary outcome measure was the proportion
      of the total preanesthesia evaluations in which the Anesthesia Nurses assisted.
      To ensure quality and safety, data on balancing measures and quality metrics were
      collected. RESULTS: The weekly percentage of outpatients evaluated by Anesthesia
      Nurses increased from 0% to 55% within the first 4 months and was then sustained.
      The remaining patients were evaluated by the Anesthesia NPs. The balancing
      measures did not show any significant negative effect. Our perioperative quality
      metrics were also not changed significantly. CONCLUSION: Using quality
      improvement methods, we successfully improved the utilization of staff resources
      by adding an Anesthesia Nurse-assisted preanesthesia evaluation program alongside
      our NPs to provide outstanding preanesthesia care at the lowest possible cost.

PMID- 25846630
TI  - Removal of bisphenol derivatives through quinone oxidation by polyphenol oxidase
      and subsequent quinone adsorption on chitosan in the heterogeneous system.
AB  - In this study, the combined use of a biopolymer chitosan and an oxidoreductase
      polyphenol oxidase (PPO) was systematically investigated for the removal of
      bisphenol derivatives from aqueous medium. The process parameters, such as the pH
      value, temperature, and PPO concentration, were estimated to conduct the
      enzymatic quinone oxidation of bisphenol derivatives by as little enzyme as
      possible. Bisphenol derivatives effectively underwent PPO-catalysed quinone
      oxidation without H2O2 unlike other oxidoreductases, such as peroxidase and
      tyrosinase, and the optimum conditions were determined to be pH 7.0 and 40
      degrees C for bisphenol B, bisphenol E, bisphenol O, and bisphenol Z; pH 7.0 and
      30 degrees C for bisphenol C and bisphenol F; and pH 8.0 and 40 degrees C for
      bisphenol T. They were completely removed through adsorption of enzymatically
      generated quinone derivatives on chitosan beads or chitosan powders. Quinone
      adsorption on chitosan beads or chitosan powders in the heterogeneous system was
      found to be a more effective procedure than generation of aggregates in the
      homogeneous system with chitosan solution. The removal time was shortened by
      increasing the amount of chitosan beads or decreasing the size of the chitosan
      powders. 

PMID- 25846631
TI  - Spectrally selective imaging with wideband balanced steady-state free precession
      MRI.
AB  - PURPOSE: Unwanted, bright fat signals in balanced steady-state free precession
      sequences are commonly suppressed using spectral shaping. Here, a new spectral
      shaping method is proposed to significantly improve the uniformity of stopband
      suppression without compromising the level of passband signals. METHODS: The
      proposed method combines binomial-pattern excitation pulses with a wideband
      balanced steady-state free precession sequence kernel. It thereby increases the
      frequency separation between the centers of pass and stopbands by pi radians,
      enabling improved water-fat contrast. Simulations were performed to find the
      optimal flip angles and subpulse spacing for the binomial pulses that maximize
      contrast and signal efficiency. RESULTS: Comparisons with a conventional binomial
      balanced steady-state free precession sequence were performed in simulations as
      well as phantom and in vivo experiments at 1.5 T and 3 T. Enhanced fat
      suppression is demonstrated in vivo with an average improvement of 58% in blood
      fat and 68% in muscle-fat contrast (P < 0.001, Wilcoxon signed-rank test).
      CONCLUSION: The proposed binomial wideband balanced steady-state free precession
      method is a promising candidate for spectrally selective imaging with enhanced
      reliability against field inhomogeneities.

PMID- 25846632
TI  - The novel desmopressin analogue [V4Q5]dDAVP inhibits angiogenesis, tumour growth
      and metastases in vasopressin type 2 receptor-expressing breast cancer models.
AB  - Desmopressin (dDAVP) is a safe haemostatic agent with previously reported
      antitumour activity. It acts as a selective agonist for the V2 vasopressin
      membrane receptor (V2r) present on tumour cells and microvasculature. The purpose
      of this study was to evaluate the novel peptide derivative [V4Q5]dDAVP in V2r
      expressing preclinical mouse models of breast cancer. We assessed antitumour
      effects of [V4Q5]dDAVP using human MCF-7 and MDA-MB-231 breast carcinoma cells,
      as well as the highly metastatic mouse F3II cell line. Effect on in vitro cancer
      cell growth was evaluated by cell proliferation and clonogenic assays. Cell cycle
      distribution was analysed by flow cytometry. In order to study the effect of
      intravenously administered [V4Q5]dDAVP on tumour growth and angiogenesis, breast
      cancer xenografts were generated in athymic mice. F3II cells were injected into
      syngeneic mice to evaluate the effect of [V4Q5]dDAVP on spontaneous and
      experimental metastatic spread. In vitro cytostatic effects of [V4Q5]dDAVP
      against breast cancer cells were greater than those of dDAVP, and associated with
      V2r-activated signal transduction and partial cell cycle arrest. In MDA-MB-231
      xenografts, [V4Q5]dDAVP (0.3 ug/kg, thrice a week) reduced tumour growth and
      angiogenesis. Treatment of F3II mammary tumour-bearing immunocompetent mice
      resulted in complete inhibition of metastatic progression. [V4Q5]dDAVP also
      displayed greater antimetastatic efficacy than dDAVP on experimental lung
      colonisation by F3II cells. The novel analogue was well tolerated in preliminary
      acute toxicology studies, at doses >= 300-fold above that required for anti
      angiogenic/antimetastatic effects. Our data establish the preclinical activity of
      [V4Q5]dDAVP in aggressive breast cancer, providing the rationale for further
      clinical trials.

PMID- 25846633
TI  - Ex vivo uranium decontamination efficiency on wounded skin and in vitro skin
      toxicity of a calixarene-loaded nanoemulsion.
AB  - The present work aims at studying the decontamination efficacy of a calixarene
      loaded nanoemulsion on two ex vivo wounded skin models mimicking superficial
      stings or cuts contaminated with uranium, and on a third model using excoriation.
      The decontaminating formulation was compared with the currently used radio
      decontaminating soapy water (Trait rouge(r)) treatment. Moreover, to assess skin
      damage potentially induced by the undiluted nanoemulsion, in vitro toxicity
      studies were conducted on an in vitro reconstructed human epidermis, coupled with
      three different toxicity tests [3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl
      tetrazolium bromide, lactate dehydrogenase, and interleukin-1-alpha]. This work
      demonstrated not only a significant decontamination activity of the calixarene
      nanoemulsion on wounded skin, ranging from 92% to 94% of the applied uranium
      solution according to the ex vivo model used, but also the absence of side
      effects of this promising treatment.

PMID- 25846634
TI  - A SNP test to identify Africanized honeybees via proportion of 'African'
      ancestry.
AB  - The honeybee, Apis mellifera, is the world's most important pollinator and is
      ubiquitous in most agricultural ecosystems. Four major evolutionary lineages and
      at least 24 subspecies are recognized. Commercial populations are mainly derived
      from subspecies originating in Europe (75-95%). The Africanized honeybee is a New
      World hybrid of A. m. scutellata from Africa and European subspecies, with the
      African component making up 50-90% of the genome. Africanized honeybees are
      considered undesirable for bee-keeping in most countries, due to their extreme
      defensiveness and poor honey production. The international trade in honeybees is
      restricted, due in part to bans on the importation of queens (and semen) from
      countries where Africanized honeybees are extant. Some desirable strains from the
      United States of America that have been bred for traits such as resistance to the
      mite Varroa destructor are unfortunately excluded from export to countries such
      as Australia due to the presence of Africanized honeybees in the USA. This study
      shows that a panel of 95 single nucleotide polymorphisms, chosen to differentiate
      between the African, Eastern European and Western European lineages, can detect
      Africanized honeybees with a high degree of confidence via ancestry assignment.
      Our panel therefore offers a valuable tool to mitigate the risks of spreading
      Africanized honeybees across the globe and may enable the resumption of queen and
      bee semen imports from the Americas.

PMID- 25846645
TI  - Knowledge, understanding, and uptake of noninvasive prenatal testing among Latina
      women.
AB  - OBJECTIVE: The aim of this study is to assess Latina patient understanding of
      noninvasive prenatal testing (NIPT) and identify what factors influence
      uptake/refusal to NIPT to adapt counseling to the needs and interests of this
      population. METHODS: Mixed-methods survey in English and Spanish administered to
      pregnant Latina patients throughout pregnancy. RESULTS: Sixty-three women
      participated in our study (67% response rate); 34.9% chose to do NIPT, and 65.1%
      declined. Approximately half of participants (44%) had an NIPT knowledge score of
      <=3 out of six total questions. Two of the most significant factors influencing
      uptake of NIPT were a higher reported educational level (p = 0.015) and a higher
      NIPT knowledge score (p = 0.014); 42.9% of participants knew that NIPT only
      screens for certain chromosomal conditions; 39% of women who declined NIPT would
      never consider NIPT in the future. CONCLUSIONS: One-third of Latina women elected
      NIPT; a higher reported educational level and language were most predictive of
      this choice. Overall knowledge was significantly lower for women who declined
      NIPT. Lower knowledge may suggest that not all women are making informed
      decisions because of varying degrees of informed consent. Providing culturally
      tailored information can help women navigate the complexities of prenatal testing
      in order to make decisions most aligned with their values.

PMID- 25846646
TI  - Subchronic administration of riparin III induces antidepressive-like effects and
      increases BDNF levels in the mouse hippocampus.
AB  - Riparin III (Rip III) is an alcamide isolated from Aniba riparia that has
      presented effects of antidepressant and anxiolytic activities in acute stress
      behavioral models. The trial's goal was to investigate the activity of Rip III in
      mice exposed to corticosterone-induced chronic depression model. Swiss female
      mice, 22-25 g, were distributed in following experimental groups: control group
      (vehicle1: saline containing 0.1% dimethyl sulfoxide and 0.1% Tween-80, SC+
      vehicle 2: distilled water emulsified with 2% Tween-80, PO); stressed group
      (corticosterone, 20 mg/kg, SC, + vehicle 2, orally); Rip III group (50 mg/kg,
      orally); and fluvoxamine (Flu) group (50 mg/kg, orally). The mice were exposed to
      the behavioral tests, and posteriorly, Brain-derived neurotrophic factor protein
      levels were assessed in hippocampal samples. Statistical analysis of the data was
      performed by one-way anova, followed by Newman-Keuls test. Both administrations
      of Rip III and Flu significantly reduced the immobility time in tail suspension
      and forced swimming tests after 21 days without affecting locomotor function.
      There was also an increase in BDNF protein levels in the mice hippocampus. These
      findings further support the hypothesis that Rip III could be a new
      pharmacological target for the treatment of mood disorders.

PMID- 25846647
TI  - Effects of treatment with androgen receptor ligands on microRNA expression of
      prostate cancer cells.
AB  - Post-transcriptional regulation by microRNA (miRNA) is an important aspect of
      androgen receptor (AR) signalling in prostate cancer cells. However, the global
      profiling of miRNA expression in prostate cancer cells following treatment with
      AR ligands has not been reported so far. In this study we examined the effect of
      treatment with two AR agonists (mibolerone (MIB) and dihydrotestosterone (DHT))
      and an AR antagonist (bicalutamide (BIC)) on miRNA expression in the human
      androgen-dependent LNCaP prostate cancer cell line using microarray technology
      and verification of selected miRNA using quantitative real-time PCR (qRT-PCR). No
      miRNA was identified as differentially expressed following treatment with the AR
      antagonist BIC. In contrast, a number of common and compound-specific alterations
      in miRNA expression were observed following treatment with AR agonists.
      Unexpectedly it was found that treatment with the AR agonists resulted in the
      repression of miR-221, a miRNA previously established to be involved with
      prostate cancer development. This observation indicates that this miRNA may have
      a more complex role in prostate cancer development than considered previously.
      Treatment with MIB led to an induction of miR-210 expression, a hypoxia-related
      miRNA. This miRNA is reported to be involved in cell adaptation to hypoxia and
      thus induction in conditions of normoxia may be important in driving metabolic
      changes observed in prostate cancer. Thus examining the effect of AR agonists and
      antagonists on miRNA expression can provide novel insights into the response of
      cells to AR ligands and subsequent downstream events. 

PMID- 25846648
TI  - Deconstructing chronic low back pain in the older adult--step by step evidence
      and expert-based recommendations for evaluation and treatment: part I: Hip
      osteoarthritis.
AB  - OBJECTIVE: To present the first in a series of articles designed to deconstruct
      chronic low back pain (CLBP) in older adults. The series presents CLBP as a
      syndrome, a final common pathway for the expression of multiple contributors
      rather than a disease localized exclusively to the lumbosacral spine. Each
      article addresses one of twelve important contributors to pain and disability in
      older adults with CLBP. This article focuses on hip osteoarthritis (OA). METHODS:
      The evaluation and treatment algorithm, a table articulating the rationale for
      the individual algorithm components, and stepped-care drug recommendations were
      developed using a modified Delphi approach. The Principal Investigator, a five
      member content expert panel and a nine-member primary care panel were involved in
      the iterative development of these materials. The algorithm was developed keeping
      in mind medications and other resources available within Veterans Health
      Administration (VHA) facilities. As panelists were not exclusive to the VHA, the
      materials can be applied in both VHA and civilian settings. The illustrative
      clinical case was taken from one of the contributor's clinical practice. RESULTS:
      We present an algorithm and supportive materials to help guide the care of older
      adults with hip OA, an important contributor to CLBP. The case illustrates an
      example of complex hip-spine syndrome, in which hip OA was an important
      contributor to disability in an older adult with CLBP. CONCLUSIONS: Hip OA is
      common and should be evaluated routinely in the older adult with CLBP so that
      appropriately targeted treatment can be designed.

PMID- 25846649
TI  - Hepatorenal syndrome: The last pieces of the puzzle or not yet?

PMID- 25846650
TI  - IL-33-induced JNK pathway activation confers gastric cancer chemotherapy
      resistance.
AB  - Inflammation is regarded as one of the major hallmarks of tumors, and has a very
      close relationship with gastric cancer. Interleukin-33 (IL-33), a new member of
      the IL-1 family, plays an important role in both inflammatory disease and tumors.
      The present study was designed to explore the effects of IL-33 on the
      proliferation, drug sensitivity, and the invasiveness of gastric cancer cells in
      vitro. IL-33 at concentrations lower than 100 pg/ml did not alter the inhibitory
      rate of gastric cancer cells. Moreover, IL-33 at these low concentrations
      protected against platinum-induced apoptosis in various gastric cancer cell
      lines, yet not in normal gastric epithelial cells. We also found that IL-33
      increased the activation of the JNK pathway, and enhanced the expression of ST2.
      Furthermore, SP600125, a selective inhibitor of the JNK pathway, significantly
      blocked the protective effects of IL-33 in gastric cancer cells. In addition,
      Matrigel invasion assay showed that IL-33 markedly promoted gastric cancer cell
      invasion. In conclusion, the present study demonstrated that IL-33 protected
      against platinum-induced apoptosis and promoted cell invasion via activation of
      the JNK pathway in gastric cancer cells. In light of the prevalence of platinum
      based chemotherapeutics in the treatment of gastric cancer, our results suggest
      that the level of IL-33 should be monitored during the treatment of gastric
      cancer, particularly when using platinum-based chemotherapeutics.

PMID- 25846651
TI  - Morbidity and mortality in systolic heart failure also associated with raised
      serum neprilysin levels.

PMID- 25846652
TI  - Response to letter regarding "Increased serum HMGB1 level may predict the fatal
      outcomes in patients with chronic heart failure".

PMID- 25846653
TI  - Influence of ischemic postconditioning on myocardial dysfunction measured by
      speckle tracking echocardiography in patients with ST-elevation myocardial
      infarction.

PMID- 25846654
TI  - Time-dependent effect of preinfarction angina pectoris and intermittent
      claudication on mortality following myocardial infarction: A Danish nationwide
      cohort study.
AB  - BACKGROUND: As proxies for local and remote ischemic preconditioning, we examined
      whether preinfarction angina pectoris and intermittent claudication influenced
      mortality following myocardial infarction. METHODS: Using medical registries, we
      conducted a nationwide population-based cohort study of all first-time myocardial
      infarction patients in Denmark during 2004-2012 (n=70,458). We computed all-cause
      and coronary mortality rate ratios (MRRs). We categorized time between
      angina/claudication presentation and subsequent myocardial infarction as 0-14, 15
      30, 31-90, and > 90 days. We adjusted for age, sex, coronary intervention,
      comorbidities, and medication use. RESULTS: Among all myocardial infarction
      patients, 18.4% had prior angina and 3.8% had prior intermittent claudication.
      Compared to patients without prior angina, the adjusted 30-day coronary MRR was
      0.85 (95% confidence interval (CI): 0.80-0.92) for stable and 0.68 (95% CI: 0.58
      0.79) for unstable angina patients. The mortality reduction increased when angina
      presented close to myocardial infarction and was higher for unstable than for
      stable angina. Thus, the 30-day coronary MRR was 0.72 (95% CI: 0.51-1.02) for
      stable angina and 0.35 (95% CI: 0.17-0.73) for unstable angina presenting within
      14 days before MI. The results were robust for all-cause mortality and in
      numerous subgroups, including women, diabetics, patients treated with PCI, and
      patients treated with and without cardioprotective drugs. Preinfarction
      intermittent claudication was associated with higher short- and long-term
      mortality compared to patients without intermittent claudication. CONCLUSIONS:
      Preinfarction angina reduced 30-day mortality, particularly when unstable angina
      closely preceded MI. Preinfarction intermittent claudication was associated with
      increased short- and long-term mortality.

PMID- 25846655
TI  - Effects of H. pylori infection on carotid intima-media thickness, serum glucose,
      serum uric acid, liver and kidney function in subjects with chronic alcohol
      ingestion.

PMID- 25846656
TI  - Current profile of infective endocarditis in intravenous drug users: The
      prognostic relevance of the valves involved.

PMID- 25846657
TI  - New-onset atrial fibrillation may be a more important predictor of cardiac
      mortality in acute myocardial infarction patients than preexisting atrial
      fibrillation.

PMID- 25846659
TI  - Acute myocardial infarction and sleep apnea.

PMID- 25846658
TI  - Comparison of the effects of two low-density lipoprotein cholesterol goals for
      secondary prevention after acute myocardial infarction in real-world practice: >=
      50% reduction from baseline versus <70 mg/dL.
AB  - BACKGROUND: The present study compared the effects of two low-density lipoprotein
      cholesterol (LDL-C) goals for secondary prevention after acute myocardial
      infarction (AMI) in real-world practice. METHODS AND RESULTS: Of 3091 consecutive
      patients with AMI who had baseline LDL-C levels >= 70 mg/dL and underwent
      successful percutaneous coronary intervention, 1305 eligible patients who
      received discharge statin prescriptions were analyzed. Patients were categorized
      into 2 groups according to the values of LDL-C at 1 year in two different manners
      using percent reduction from baseline (>= 50% reduction, n=428 versus <50%
      reduction, n=877) and fixed levels (< 70 mg/dL, n=625 versus >= 70 mg/dL, n=680).
      The primary outcome was defined by the composite of 2-year major cardiac events
      including cardiac death, non-fatal myocardial infarction, percutaneous coronary
      intervention, and coronary artery bypass grafting after hospital discharge. At 2
      years, major cardiac events occurred in 139 patients (10.7%). Compared with <50%
      LDL-C reduction from baseline, patients with >= 50% LDL-C reduction had a 47%
      risk reduction in major cardiac events (adjusted hazard ratio, 0.53; 95%
      confidence interval, 0.36 to 0.79; P=0.002). But, compared with LDL-C levels >=
      70 mg/dL at 1 year, patients with LDL-C levels < 70 mg/dL at 1 year had a similar
      risk of major cardiac events (adjusted hazard ratio, 0.96; 95% confidence
      interval, 0.68 to 1.34; P=0.793). CONCLUSIONS: Obtaining a >= 50% reduction in
      LDL-C was associated with better clinical outcomes after AMI in real-world
      practice, whereas achieving a < 70 mg/dL was not.

PMID- 25846660
TI  - Impacts of valve intervention on the Functional REServe of the Heart: The FRESH
      valve pilot study.
AB  - PURPOSE: Severe valve lesions require corrective interventions to avoid
      progression to heart failure (HF) and premature demise. We tested the hypothesis
      that despite operative risks, corrective valvular interventions will lead to
      significant improvements in overall cardiac pump function, especially before the
      onset of cardiac decompensation. METHODS: We compared the cardiopulmonary
      exercise performance and non-invasive haemodynamics of 46 consecutive patients
      with severe valvular disease before and after valvular intervention with
      reference to 101 healthy male and 139 female controls without cardiovascular
      disease. Cardiac and physical functional reserves were measured with standard
      respiratory gas analyses and CO2 rebreathing to measure cardiac output non
      invasively during peak treadmill exercise. Data are given as mean +/- SD and
      statistical significance accepted at P<0.05. RESULTS: The entire patient cohort
      showed no significant improvement in peak O2 consumption (VO2max, P=0.74) or in
      peak cardiac power (CPOmax, P=0.34) after valvular intervention, but we found
      instead a dichotomous outcome depending on preoperative cardiac function: (i) the
      pre-operative cardiac decompensatory subgroup (LoW, n=26) showed increased CPOmax
      (2.63 +/- 0.67 to 3.42 +/- 0.98 W, P<0.0001) and VO2max (1.38 +/- 0.55 to 1.56 +/
      0.59 L.min(-1), P<0.01); and (ii) the pre-operative non-decompensatory subgroup
      (HiW) showed reduced CPOmax (4.58 +/- 0.96 to 3.84 +/- 0.92 W, P<0.001) and
      VO2max (2.29 +/- 0.72 to 1.97 +/- 0.75 L.min(-1), P<0.01). Changes in NYHA class
      were found to be discrepant with these objective measurements. CONCLUSION: This
      investigation found an unexpected finding that valvular interventions performed
      in routine clinical practice do not consistently improve cardiac function,
      especially in those without pre-operative cardiac decompensation. Assessing
      cardiac functional gains would open up new avenues for future trials of valvular
      interventions.

PMID- 25846661
TI  - Ticagrelor increases endothelial progenitor cell level compared to clopidogrel in
      acute coronary syndromes: A prospective randomized study.
AB  - BACKGROUND: The clinical benefit of ticagrelor compared to clopidogrel in ACS
      patients suggested off-target property. Such pleiotropic effect could be mediated
      by circulating endothelial progenitor cells (EPC) which are critical for vascular
      healing. We aimed to investigate the impact of ticagrelor on EPC in acute
      coronary syndrome (ACS) patients undergoing percutaneous coronary intervention
      (PCI). METHODS: We prospectively randomized 106 ACS patients to ticagrelor or
      clopidogrel. Sub-populations of CD34+ circulating progenitor cells (PC) were
      analyzed by flow cytometry allowing one to determine the levels of CD34+ PC,
      CD34+CD45+ Hematopoietic PC, CD34+133+ immature PC and CD34+KDR+ EPC on admission
      and at 1 month. Changes in PC level were calculated as the difference between 1
      month and baseline value. RESULTS: The 2 groups were similar regarding baseline
      characteristics including PC numbers on admission. The 2 groups had similar
      change in overall CD34+ PC and hematopoietic CD34+45+ PC level (p=0.2). On the
      contrary, when considering CD34+133+ PC and CD34+KDR+ EPC, we observed that
      patients treated by ticagrelor had a significantly higher increase in levels of
      these PC subtypes compared to those treated by clopidogrel (0.23 (-0.33; 0.79) vs
      0.00 (-0.5; 0.34); p=0.04 and 0.01 (-0.04; 0.05) vs -0.01 (-0.06; 0.03); p=0.02).
      Changes in the level of CD34+CD133+ PC correlated with platelet activity measured
      by the VASP index (r=-0.30; p=0.008). By contrast the increase in the level of
      CD34+KDR+ EPC in the ticagrelor group was independent of platelet activity.
      CONCLUSIONS: Ticagrelor increases the number of EPC in ACS patients suggesting a
      benefit on endothelial regeneration that may participate in the pleiotropic
      property of the drug.

PMID- 25846662
TI  - Left anterior descending coronary artery fistula to left ventricle: The revenge
      of a well treated myocardial infarction in the era of primary percutaneous
      angioplasty.

PMID- 25846663
TI  - Ticagrelor related dyspnea in patients with acute coronary syndromes: Incidence
      and implication on ticagrelor withdrawn.

PMID- 25846664
TI  - Below the poverty line and non-communicable diseases in Kerala: The Epidemiology
      of Non-communicable Diseases in Rural Areas (ENDIRA) study.
AB  - INTRODUCTION: India carries the greatest burden of global non-communicable
      diseases (NCDs). Poverty is strongly associated with NCDs but there are few
      prevalence studies which have measured poverty in India, particularly in rural
      settings. METHODS: In Kerala, India, a population of 113,462 individuals was
      identified. The "Epidemiology of Non-communicable Diseases in Rural Areas"
      (ENDIRA) study was conducted via ASHAs (Accredited Social Health Activists).
      Standardised questionnaires were used in household interviews of individuals
      >=18years during 2012 to gather sociodemographic, lifestyle and medical data for
      this population. The Government of Kerala definition of "the poverty line" was
      used. The association between below poverty line (BPL) status, NCDs and risk
      factors was analysed in multivariable regression models. RESULTS: 84,456 adults
      were included in the analyses (25.4% below the poverty line). The prevalence of
      NCDs was relatively common: myocardial infarction (MI) 1.4%, stroke 0.3%,
      respiratory diseases 5.0%, and cancer 1.1%. BPL status was not associated with
      age (p=0.96) or gender (p=0.26). Compared with those above the poverty line
      (APL), the BPL group was less likely to have diabetes, hypertension or
      dyslipidaemia (p<0.0001), and more likely to smoke (p<0.0001). Compared with APL,
      BPL was associated with stroke (OR 1.33, 1.04-1.69; p=0.02) and respiratory
      disease (OR 1.23, 1.15-1.32; p<0.0001) in multivariable analyses, but not MI or
      cancer. CONCLUSIONS: In rural Kerala, BPL status was associated with stroke and
      respiratory diseases, but not with MI and cancer although it was associated with
      smoking status, compared with above poverty line status.

PMID- 25846665
TI  - Reasons for non-adherence to practice guidelines on stroke prevention in patients
      with atrial fibrillation: A cross-sectional study in primary care.

PMID- 25846666
TI  - Bailout left main bioresorbable vascular scaffolding for the treatment of
      iatrogenic coronary dissection induced by guiding catheter and sticky ABSORB
      bioresorbable vascular scaffold balloon.

PMID- 25846667
TI  - Novel presentation of Pompe disease: Inclusion-body myositis-like clinical
      phenotype.

PMID- 25846668
TI  - Damage to the insula is associated with abnormal interpersonal trust.
AB  - Reciprocal trust is a crucial component of cooperative, mutually beneficial
      social relationships. Previous research using tasks that require judging and
      developing interpersonal trust has suggested that the insula may be an important
      brain region underlying these processes (King-Casas et al., 2008). Here, using a
      neuropsychological approach, we investigated the role of the insula in reciprocal
      trust during the Trust Game (TG), an interpersonal economic exchange. Consistent
      with previous research, we found that neurologically normal adults reciprocate
      trust in kind, i.e., they increase trust in response to increases from their
      partners, and decrease trust in response to decreases. In contrast, individuals
      with damage to the insula displayed abnormal expressions of trust. Specifically,
      these individuals behaved benevolently (expressing misplaced trust) when playing
      the role of investor, and malevolently (violating their partner's trust) when
      playing the role of the trustee. Our findings lend further support to the idea
      that the insula is important for expressing normal interpersonal trust, perhaps
      because the insula helps to recognize risk during decision-making and to identify
      social norm violations. 

PMID- 25846670
TI  - Response to "Cryolipolysis: The Importance of Scientific Evaluation of a New
      Technique".

PMID- 25846669
TI  - Adoptive T cell therapy combined with intralesional administrations of TG1042
      (adenovirus expressing interferon-gamma) in metastatic melanoma patients.
AB  - Tumor immune escape has recently been shown to be related to the development of
      an immune tolerance state of the microenvironment. Cytokines activating the
      immune system such as IFN-gamma can be used to reverse the immune escape and thus
      to potentiate the efficacy of immunotherapy. A clinical study was conducted in 18
      stage IIIc/IV melanoma patients treated with tumor-infiltrating lymphocytes
      (TILs) in combination with intratumoral TG1042 injection (adenovirus expressing
      IFN-gamma). The primary objective was to investigate the safety of treatment.
      Secondary objectives were to study the clinical response and translational
      research. The treatment was well tolerated. Among the 13 patients evaluable for
      tumor response, 38.5% had an overall objective response (OOR = CR + PR) and
      disease control rate (DCR = CR + PR + S) of 46%. The clinical response of the 37
      targeted lesions led to an OOR of 51% and a DCR of 75%. Translational research on
      predictive markers did not significantly differ between responder and non
      responder patients. However, specifically regarding injected lesions, the
      clinical response correlated with CD3-/CD56+ NK cells which could be activated by
      TG1042. Further larger studies of this combined immunotherapy are needed to
      confirm our findings. Intralesional TG1042 combined with antigen-selected TILs
      should be discussed.

PMID- 25846671
TI  - Pulmonary mycobacterial spindle cell pseudotumor in a lung transplant patient:
      progression without therapy and response to therapy.
AB  - Mycobacterial spindle cell pseudotumor (MSP) represents a rare, non-malignant,
      mass-forming reaction to various mycobacterial infections, typically occurring in
      immunocompromised patients. It is characterized by the proliferation of spindle
      shaped fibrohistiocytic cells without the formation of epithelioid granulomas.
      Without staining for acid-fast bacilli, histological distinction from other
      spindle cell lesions, including malignancy, can be difficult. Most of the MSP
      cases reported in the literature have involved lymph nodes, skin, spleen, or bone
      marrow, but rarely involve the lung. MSP predominately occurs in patients who are
      immunosuppressed. We present a patient with MSP of the transplanted lung caused
      by non-tuberculous mycobacteria, in whom both the natural course of the untreated
      pseudotumor as well as the response to antimycobacterial treatments were
      observed.

PMID- 25846672
TI  - Incidence and weight trajectories of binge eating disorder among young women in
      the community.
AB  - OBJECTIVE: To assess the population prevalence and incidence of binge eating
      disorder (BED) among young women. METHOD: In a nationwide longitudinal study of
      Finnish twins born 1975-1979, the women participated in five surveys from age 16
      until their mid-thirties. At Wave 4 (mean age 24 years), the women (N = 2,825)
      underwent a 2-stage screening for eating disorders. We assessed the lifetime
      prevalence, incidence, and clinical characteristics of DSM-5 BED. RESULTS: We
      detected 16 women who met DSM-5 criteria for BED, yielding a lifetime prevalence
      of 0.7% (95% confidence interval [CI] 0.4-1.2%). The incidence of BED among women
      between 10 and 24 years of age was 35 (95% CI 20-60) per 100,000 person-years.
      The mean age of onset of BED was 19 years (range 13-27 years). Of the cases,
      13/16 (81%) were currently ill. Duration of illness at the time of assessment
      ranged from less than a year to 13 years (median 6 years). Of women with BED,
      only two had a history of other eating disorders, but six had lifetime major
      depressive disorder. Two-thirds of the women with BED belonged to the highest
      weight quartile at age 16, and their mean BMI at age 22-27 year was 26.2 kg/m(2)
      (range 22.1-32.5 kg/m(2)). DISCUSSION: Incident BED as defined by DSM-5 was
      relatively rare among younger women and was often preceded by relative
      overweight. BED often occurred without a history of other eating disorders, but
      comorbidity with major depressive disorder was common.

PMID- 25846673
TI  - Complete myocardial revascularization confers a larger clinical benefit when
      performed with state-of-the-art techniques in high-risk patients with multivessel
      coronary artery disease: A meta-analysis of randomized and observational studies.
AB  - OBJECTIVES: To test whether a strategy of complete revascularization (CR) as
      compared with incomplete myocardial revascularization (IR)-both performed with
      current "state-of-the-art" percutaneous coronary interventions (PCI) or coronary
      artery bypass graft (CABG)-would provide a clinical benefit in patients with
      multivessel coronary artery disease (MVCAD). BACKGROUND: The "optimal" extent of
      myocardial revascularization remains to be determined. METHODS: We performed a
      meta-analysis of studies reporting on clinical outcomes of MVCAD patients treated
      with CR and IR, with extensive (>80%) use of stents for PCI or arterial conduits
      in CABG. Relative risk (RR) and 95% confidence intervals (CIs) for all-cause
      mortality were assessed as primary endpoint, myocardial infarction (MI) and
      repeat revascularization as secondary endpoints. RESULTS: A total of 28 studies
      were identified, including 83,695 patients with 4.7 +/- 4.3 years of follow-up.
      Compared with IR, CR was associated with reduced mortality (RR: 0.73; 95% CI 0.66
      0.81) both after CABG (RR: 0.76; 95% CI 0.63-0.90) and PCI (RR: 0.73; 95% CI 0.64
      0.82). The risks of MI (RR: 0.74; 95% CI 0.64-0.85) and repeat revascularization
      (RR: 0.77; 95% CI 0.66-0.88) were also lower after CR as compared with IR.
      Metaregression showed a significant RR reduction of MI associated with more
      recent publication (P = 0.021) and increasing prevalence of diabetes (P = 0.033).
      CONCLUSIONS: In MVCAD, as compared with IR, CR confers a clinical benefit that
      seems larger in cohorts of patients enrolled in more recent studies and with a
      higher prevalence of diabetes. (c) 2015 Wiley Periodicals, Inc.

PMID- 25846674
TI  - RPL10 mutation segregating in a family with X-linked syndromic Intellectual
      Disability.
AB  - Intellectual disability is a neurodevelopmental disorder of impaired adaptive
      skills and low intelligence quotient. The overall prevalence is estimated at 2-3%
      in the general population with extreme clinical and genetic heterogeneity, and it
      has been associated with possibly causative mutations in more than 700 identified
      genes. In a recent review, among over 100 X-linked intellectual disability
      causative genes, eight were reported as "awaiting replication." Exome sequencing
      in a large family identified a missense mutation in RPL10 highly suggestive of X
      linked intellectual disability. Herein, we report on the clinical description of
      four affected males. All patients presented apparent intellectual disability
      (4/4), psychomotor delay (4/4) with syndromic features including amniotic fluid
      excess (3/4), microcephaly (2/4), urogenital anomalies (3/4), cerebellar syndrome
      (2/4), and facial dysmorphism. In the literature, two mutations were reported in
      three families with affected males presenting with autism. This report confirms
      the implication of RPL10 mutations in neurodevelopmental disorders and extends
      the associated clinical spectrum from autism to syndromic intellectual
      disability.

PMID- 25846675
TI  - Improved and versatile viral 2A platforms for dependable and inducible high-level
      expression of dicistronic nuclear genes in Chlamydomonas reinhardtii.
AB  - A significantly improved viral 2A peptide system for dependable high-level
      expression of dicistronic genes in Chlamydomonas reinhardtii has been developed.
      Data are presented demonstrating that use of an especially proficient 'extended
      FMDV 2A' coding region allows production of two independent protein products from
      a dicistronic gene with almost complete efficiency. Importantly, results are also
      presented that demonstrate the utility of this 2A system for efficient high-level
      expression of foreign genes in C. reinhardtii, which has not previously been
      reliably achievable in this algal model system. To expand the versatility of the
      2A expression system, a number of commonly used selectable marker proteins were
      assessed for their compatibility with the extended FMDV 2A peptide. Additional
      experiments demonstrate the feasibility and utility of 2A-containing dicistronic
      systems that rely on a strong conditional promoter for transcriptional control
      and a low-expression marker gene for selection. This strategy allows easy and
      efficient delivery of genes of interest whose expression levels require
      regulation either to mitigate potential toxicity or allow differential expression
      under controlled experimental conditions. Finally, as an additional practical
      demonstration of the utility of the extended FMDV 2A system, confocal
      fluorescence microscopy is used to demonstrate that native and foreign proteins
      of interest bearing post-translational remnants of the extended FMDV 2A peptide
      localize correctly to various cellular compartments, including a striking
      demonstration of the almost exclusive localization of the Rubisco small subunit
      protein to the pyrenoid of the C. reinhardtii chloroplast in cells maintained
      under ambient CO2 concentrations. 

PMID- 25846676
TI  - Electron-deficient fullerenes in triple-channel photosystems.
AB  - Fullerenes of increasing electron deficiency are designed, synthesized and
      evaluated in multicomponent surface architectures to ultimately build gradients
      in LUMO levels with nine components over 350 meV down to -4.22 eV. 

PMID- 25846677
TI  - An Iron Oxide Nanocarrier Loaded with a Pt(IV) Prodrug and Immunostimulatory
      dsRNA for Combining Complementary Cancer Killing Effects.
AB  - There is major current interest in harnessing the immune system against cancer
      and in developing drugs that provide complementary cancer killing mechanisms.
      Although the recent advent of nanoparticle-based drug delivery systems has
      improved the efficacy of platinum drugs for chemotherapy, one of the fundamental
      paradigms in their design and use is evading surveillance by the immune system to
      enhance anticancer efficacy. However, new studies are showing that chemotherapy
      can profit from actively targeting stimulation of the immune system and that
      suitably functionalized nanomaterials might be ideal for overcoming some key
      challenges in immunotherapy. Pt(IV) prodrug-modified PEGylated phospholipid
      micelles that encapsulate biocompatible iron oxide nanoparticles (IONPs) as a new
      delivery system for cisplatin are reported. The Pt(IV)-IONPs are functionalized
      with polyinosinic-polycytidylic acid (poly (I:C))--a double stranded RNA (dsRNA)
      analog widely used as an adjuvant in clinical trials of cancer immunotherapy. The
      Pt(IV)-IONPs and poly (I:C)--Pt(IV)-IONPs enhance by more than an order of
      magnitude the prodrug cytotoxicity in different tumor cells, while greatly
      increasing the ability of cisplatin and poly (I:C) to activate dendritic cells-
      the key cellular players in immunotherapy. The results suggest that these
      constructs hold promise for targeted chemoimmunotherapy.

PMID- 25846684
TI  - Addressing requests for emergency ultrasonographic examinations when implementing
      teleradiology services.
AB  - PURPOSE: To prospectively assess how to address requests for ultrasonographic
      examinations when setting up an on-call teleradiology service. MATERIALS AND
      METHODS: An analytical prospective study was performed from January 2012 to
      December 2012 inclusively. All requests received for after-hours ultrasonographic
      examinations during this period were analyzed. Ultrasound requests were
      classified as being postponable until working hours, replaceable by an alternate
      cross-sectional imaging modality, or urgent and needing to be performed after
      hours. RESULTS: A total of 176 requests for ultrasonographic examinations were
      analyzed. They predominantly included requests for abdominal and pelvic
      ultrasonographic examinations (63%). Thirty-nine requests (22.2%) were considered
      as postponable, 49 (27.8%) as replaceable and 64 (36.4%) as both postponable and
      replaceable. Twenty-four requests (13.6%) were considered as urgent; they
      consisted of 10 requests for venous duplex Doppler ultrasonographic examinations
      of the lower limbs, eight requests for testicular ultrasonographic examinations,
      five for pelvic ultrasonographic examinations and one for soft-tissue
      ultrasonographic examination. In these urgent cases, realistic options were
      either to transfer the patient to another institution or to train emergency
      department physicians in ultrasonography for local handling. CONCLUSION: Although
      the need for addressing requests for ultrasonographic examinations should be
      taken into account when setting up an on-call teleradiology service, it should
      not impede such plans.

PMID- 25846685
TI  - The difference in congenital cholesteatoma CT findings based on the type of mass.
AB  - OBJECTIVE: A retrospective assessment of differences in congenital cholesteatoma
      CT findings with a focus on type of cholesteatoma mass. MATERIALS AND METHODS:
      The medical records and CT images of 14 patients with congenital cholesteatomas
      in the middle ear who underwent surgery at our institution between January 2009
      and July 2014 were reviewed. Cholesteatomas were classified as closed type, open
      type, or mixed type based on intraoperative findings. The CT findings including
      cholesteatoma size, location, and shape were retrospectively reviewed. RESULTS:
      Eight patients had closed type cholesteatomas, four had mixed type, and two had
      open type. The mean size of all cholesteatomas was 5.1mm. None of the
      cholesteatoma types indicated a tendency towards a certain location. The round
      shape was observed more frequently in closed type cholesteatomas than in other
      types (closed: 5/8; mixed: 1/4; open: 0/2). Two large closed type cholseteatomas
      and two mixed type cholesteatomas exhibited a constricted shape. Both of the open
      type cholesteatomas displayed an irregular shape. CONCLUSION: Small closed type
      congenital cholesteatomas were typically observed as round shaped lesions, but
      large closed type cholesteatomas and other type cholesteatomas tended to display
      shapes other than round.

PMID- 25846686
TI  - Extra-intestinal malignancies in inflammatory bowel diseases: An update with
      emphasis on MDCT and MR imaging features.
AB  - Inflammatory bowel diseases (IBD) are associated with an increased risk of
      gastrointestinal cancers and more specifically in sites affected by chronic
      inflammation. However, patients with IBD have also an increased risk for
      developing a variety of extra-intestinal cancers. In this regard, hepatobiliary
      cancers, such as cholangiocarcinoma, are more frequently observed in IBD patients
      because of a high prevalence of primary sclerosing cholangitis, which is
      considered as a favoring condition. Extra-intestinal lymphomas, mostly non
      Hodgkin lymphomas, and skin cancers are also observed with an increased incidence
      in IBD patients by comparison with that in patients without IBD. This review
      provides an update on demographics, risk factors and clinical features of extra
      intestinal malignancies, including cholangiocarcinoma, hepatocellular carcinoma
      and lymphoma, that occur in patients with IBD along with a special emphasis on
      the multidetector row computed tomography and magnetic resonance imaging features
      of these uncommon conditions. 

PMID- 25846688
TI  - An uncommon cause of left upper abdominal pain.

PMID- 25846689
TI  - Epidermoid splenic cyst.

PMID- 25846690
TI  - Association of ABCB1 C3435T polymorphism with phenobarbital resistance in Thai
      patients with epilepsy.
AB  - WHAT IS KNOWN AND OBJECTIVE: One-third of patients with epilepsy are resistant to
      anti-epileptic drugs (AEDs). Drug-resistant epilepsy is believed to be
      multifactorial involving both genetic and non-genetic factors. Genetic variations
      in the ABCB1 gene encoding the drug efflux transporter, p-glycoprotein (p-gp),
      may influence the interindividual variability in AED response by limiting drugs
      from reaching their target. Phenobarbital (PB), one of the most cost-effective
      and widely used AEDs in developing countries, has been reported to be transported
      by p-gp. This study aimed to investigate the association of a genetic variant,
      ABCB1 3435C>T, and non-genetic factors with phenobarbital response in Thai
      patients with epilepsy. METHODS: One hundred and ten Thai patients with epilepsy
      who were treated with PB maintenance doses were enrolled in this study. Two
      phenotypic groups, PB-responsive epilepsy and PB-resistant epilepsy, were defined
      according to the International League Against Epilepsy (ILAE) criteria. Subjects
      were genotyped for ABCB1 3435C>T (rs1045642). Multiple logistic regression
      analysis was tested for the association of ABCB1 3435C>T polymorphism and non
      genetic factors with PB response. RESULTS AND DISCUSSION: Sixty-two PB-responsive
      epilepsy subjects and 48 PB-resistant epilepsy subjects were identified. All
      genotype frequencies of the ABCB1 3435C>T SNP were consistent with the Hardy
      Weinberg equilibrium (P > 0.05). The ABCB1 3435C>T polymorphism and type of
      epilepsy were associated with response to PB. Patients with PB-resistant epilepsy
      had a significantly higher frequency of ABCB1 3435CC genotype and had focal
      epilepsy more often than patients with PB-responsive epilepsy (adjusted OR =
      3.962, 95% CI = 1.075-14.610, P-value = 0.039; adjusted OR = 5.936, 95% CI =
      2.272-15.513, P-value < 0.001, respectively). The model explained 25.5% of the
      variability in response to PB (R(2)  = 0.255). WHAT IS NEW AND CONCLUSION: Thai
      patients of ABCB1 3435CC genotype and with focal epilepsy were more often PB
      resistant. Those two factors partly account for the variability in Thai epilepsy
      patients' response to phenobarbital.

PMID- 25846696
TI  - Can the height-independent Pottel eGFR equation be used as a screening tool for
      chronic kidney disease in children?
AB  - Determination of plasma creatinine (Pcr) should be associated to an estimation of
      glomerular filtration rate (eGFR). Pottel et al. established a height-independent
      equation, eGFR = 107.3/(Pcr/Q) where Q is the median of Pcr (Pottel-Belgium). The
      aims were to 1) determine a local height-independent equation (Pottel-Lyon), 2)
      evaluate the performance of these equations compared to the Schwartz 2009 and
      Schwartz-Lyon equations, and 3) evaluate the height-independent equations in
      laboratory routine. Therefore, 1) all first pediatric Pcr determination (December
      2009-June 2011) were collected, and median of Pcr was determined for each 1-year
      age interval (Q-Lyon), 2) GFR was measured (mGFR) in 359 children (438 measures)
      and compared to eGFR, and 3) all first Pcr determination (January 2012-June 2013)
      were used to calculate eGFR with the Pottel-Lyon and the Pottel-Belgium
      equations. Pcr was determined by an IDMS-standardized enzymatic assay. In the
      population with a mGFR, the Pottel-Lyon and the Schwartz-Lyon showed the best
      performance (bias, P10 and P30). However, the performance in identifying patients
      with a mGFR < 75 mL/min/1.73 m(2) was similar for all the studied equations.
      CONCLUSION: The performance of the height-independent and dependent equations to
      identify mild renal dysfunction is similar. The height-independent Pottel
      equation could be proposed as an excellent screening tool for kidney disease when
      height information is not available. " WHAT IS KNOWN: " * Determination of plasma
      creatinine in children is rarely associated to an estimation of glomerular
      filtration rate due to the lack of height information. * Pottel et al. developed
      a height-independent equation (eGFR = 107.3/(Pcr/Q) where Q is the median of Pcr
      for each age class. " WHAT IS NEW: " * The performance of the height-independent
      (Pottel) or height-dependent (Schwartz) equations is similar to identify renal
      dysfunction (GFR < 75 mL/min/1.73 m (2) ) in children. * The height-independent
      Pottel equation could be an excellent screening tool for kidney disease in a
      general pediatric laboratory when height information is not available.

PMID- 25846697
TI  - Work stress, burnout, and perceived quality of care: a cross-sectional study
      among hospital pediatricians.
AB  - Poor hospital work environments affect physicians' work stress. With a focus on
      hospital pediatricians, we sought to investigate associations between work
      stress, burnout, and quality of care. A cross-sectional study was conducted in N
      = 96 pediatricians of a German academic children's hospital (response rate = 73.8
      %). All variables were assessed with standardized questionnaires. Multivariate
      regression analyses were applied to investigate associations after adjusting for
      potential confounders. Critically high work stress (effort/reward ratio, ERR >
      1.0) was reported by N = 25 (28.4 %) participants. Pediatricians in inpatient
      wards had significantly more work stress than their colleagues in intensive care
      units and outpatient wards; 10.2 % of surveyed pediatricians reported critically
      high burnout. Again, inpatient ward staff reported significantly increased
      emotional exhaustion. After controlling for several confounders, we found that
      pediatricians with high work stress and emotional exhaustion reported reduced
      quality of care. Mediation analyses revealed that especially pediatricians'
      emotional exhaustion partially mediated the effect of work stress on quality of
      care. CONCLUSION: Results demonstrate close relationships between increased work
      stress and burnout as well as diminished quality of care. High work stress
      environments in pediatric care influence mental health of pediatricians as well
      as quality of patient care. WHAT IS KNOWN: * The quality of pediatricians' work
      environment in the hospital is associated with their work stress and burnout. *
      The consequences of pediatricians' work life for the quality of care need to be
      addressed in order to inform interventions to improve work life and care quality.
      WHAT IS NEW: * Our study shows associations between increased work stress and
      burnout with mitigated quality of care. * Beyond indirect effects of work stress
      through emotional exhaustion on quality of care we also observed direct
      detrimental effects of pediatricians' work stress on mitigated care quality.

PMID- 25846698
TI  - Uterine rupture: trends over 40 years.
AB  - OBJECTIVE: To follow trends of uterine rupture over a period of 40 years in
      Norway. DESIGN: Population-based study using data from the Medical Birth
      Registry, the Patient Administration System, and medical records. SETTING:
      Norway. SAMPLE: Women giving birth in 21 maternity units in Norway during the
      period 1967-2008 (n = 1 441 712 maternities). METHODS: The incidence and outcomes
      of uterine rupture were compared across four decades: 1967-1977; 1978-1988; 1989
      1999; and 2000-2008. Multivariable logistic regression was used to determine the
      odds ratio (OR) for uterine rupture in each decade compared with the second
      decade. MAIN OUTCOME MEASURE: Trends in uterine rupture. RESULTS: We identified
      359 uterine ruptures. The incidence rates per 10 000 maternities in the first,
      second, third, and fourth decade were 1.2, 0.9, 1.7, and 6.1, respectively. The
      ORs for complete and partial ruptures in the fourth versus the second decade were
      6.4 (95% confidence interval, 95% CI 3.8-10.8) and 7.2 (95% CI 4.2-12.3),
      respectively. Significant contributing factors to this increase were the higher
      rates of labour augmentation with oxytocin, scarred uteri from a previous
      caesarean section, and labour induction with prostaglandins or prostaglandins
      combined with oxytocin. After adjusting for risk factors, the ORs for complete
      and partial ruptures were 2.2 (95% CI 1.3-3.8) and 2.8 (95% CI 1.6-4.8),
      respectively. Severe postpartum haemorrhage, hysterectomy, intrapartum death and
      infant death after complete uterine ruptures decreased significantly over time.
      CONCLUSIONS: A sharply increasing trend of uterine rupture was found. Obstetric
      interventions contributed to this increase, but could not explain it entirely.
      TWEETABLE ABSTRACT: A sharply increasing trend of uterine ruptures has been found
      in Norway in recent years.

PMID- 25846700
TI  - A Cascade-Reaction Nanoreactor Composed of a Bifunctional Molecularly Imprinted
      Polymer that Contains Pt Nanoparticles.
AB  - This study was aimed at addressing the present challenge of cascade reactions,
      namely, how to furnish the catalysts with desired and hierarchical catalytic
      ability. This issue was addressed by constructing a cascade-reaction nanoreactor
      made of a bifunctional molecularly imprinted polymer containing acidic catalytic
      sites and Pt nanoparticles. The acidic catalytic sites within the imprinted
      polymer allowed one specified reaction, whereas the encapsulated Pt nanoparticles
      were responsible for another coupled reaction. To that end, the unique imprinted
      polymer was fabricated by using two well-coupled templates, that is, 4
      nitrophenyl acetate and 4-nitrophenol. The catalytic hydrolysis of the former
      compound at the acidic catalytic sites led to the formation of the latter
      compound, which was further reduced by the encapsulated Pt nanoparticles to 4
      aminophenol. Therefore, this nanoreactor demonstrated a catalytic-cascade
      ability. This protocol opens up the opportunity to develop functional catalysts
      for complicated chemical processes. 

PMID- 25846699
TI  - Influenza virus antigenicity and broadly neutralizing epitopes.
AB  - A vaccine formulation that would be effective against all strains of influenza
      virus has long been a goal of vaccine developers, but antibodies after infection
      or vaccination were seen to be strain specific and there was little evidence of
      cross-reactive antibodies that neutralized across subtypes. Recently a number of
      broadly neutralizing monoclonal antibodies have been characterized. This review
      describes the different classes of broadly neutralizing antibodies and discusses
      the potential of their therapeutic use or for design of immunogens that induce a
      high proportion of broadly neutralizing antibodies. 

PMID- 25846701
TI  - Prevalence of Psychiatric Disorders Among Turkish Children: The Effects of
      Impairment and Sociodemographic Correlates.
AB  - This study was designed to assess the prevalence of psychiatric disorders and the
      impact of impairment criteria on rates of diagnoses in a representative sample of
      elementary school children from a country in a region. We sampled 419 primary
      school children by using a one-stage design in Izmir, Turkey. The response rate
      was 99.5 % and 417 cases were assessed using the Schedule for Affective Disorders
      and Schizophrenia for School-Age Children Present and Lifetime Version and a
      scale to assess the impairment criterion. The results showed that 36.7 % of the
      sample met DSM-IV criteria independent of impairment and that 14.1 % of the
      population had one or more DSM-IV disorders when a measure of impairment specific
      to each diagnosis was considered. The most prevalent disorders were attention
      deficit/hyperactivity disorder and anxiety disorders. This study provided the
      first estimates of the prevalence of specific DSM-IV-defined psychiatric
      disorders in Turkish population of children. 

PMID- 25846702
TI  - Weight estimation in paediatric resuscitation: A hefty issue in New Zealand.
AB  - OBJECTIVE: To test the accuracy of weight estimation methods currently used in
      New Zealand to predict a child's weight in emergency resuscitation. METHODS: A
      prospective, observational study. Data were collected in July 2013 at five
      Auckland schools among children aged 5-10 years. Collected demographic
      information included age, ethnicity, sex and school decile. Standardised measures
      included weight, height and Broselow-Luten tape (2011 version, limited to
      children 43-143 cm) weight. Age-based weight estimates were calculated for APLS,
      Shann and Theron formulae. Mean bias (actual weight - estimated weight) and
      clinical accuracy (proportion of estimates within 10% of actual weight) are
      reported. Bland-Altman plots illustrate agreement and 95% limits of agreement.
      RESULTS: The 376 participants weighed between 14.2 and 93.1 kg. The proportion of
      weight estimates within 10% of actual weight were 28.7%, 39.1% and 45.7% for the
      age-based formula (Theron, APLS and Shann, respectively). The mean bias was
      negative for Theron (-6.5) and positive for APLS (7.8) and Shann (7.7). For the
      length-based Broselow-Luten tape method (n = 305), the proportion of weight
      estimates within 10% of actual weight was 73.4% and mean bias was 1.1.
      CONCLUSION: For children under 143 cm in height, the Broselow-Luten tape
      outperforms other weight estimation methods, accurately estimating weight in
      approximately three out of four children. The age-based estimation methods
      performed poorly overall, with variation by age and ethnicity.

PMID- 25846703
TI  - Stepping up, stepping back, stepping forward: Student nurses' experiences as peer
      mentors in a pre-nursing scholarship.
AB  - Mentorship is an essential part of the registered nurse's role, yet few
      opportunities exist for student nurses to mentor others during pre-registration
      programmes. This paper reports student nurses' experiences of mentoring school
      pupils during a pre-nursing scholarship. Focus groups were conducted with fifteen
      final year student nurses (14 female, 1 male) in two university campuses in
      Scotland. Discussions were audio recorded and transcribed verbatim, and data
      analysed thematically. Three interconnected themes emerged: 1) stepping up; 2)
      stepping back; 3) stepping forward. 'Stepping up' was a process through which
      student nurses rapidly assumed responsibility for mentoring pupils, facilitated
      through the attitudes and actions of students' mentors and students' control over
      pupils' practice experiences. 'Stepping back' encapsulated attitudes and
      behaviours that enabled student nurses to mentor pupils that involved
      considerable judgement around how unfolding events in practice could provide
      learning and development opportunities, and emotional acuity to support pupils
      through, sometimes challenging, practice situations. 'Stepping forward' described
      how students' mentoring experience allowed them to appraise and affirm nursing
      knowledge and skills, and gain greater appreciation of the reality and complexity
      of mentorship in clinical practice. Peer mentoring may prepare student nurses for
      future mentoring roles and aid their transition into clinical practice. 

PMID- 25846704
TI  - Generation of Helios reporter mice and an evaluation of the suppressive capacity
      of Helios(+) regulatory T cells in vitro.
AB  - Helios is a member of the Ikaros transcription factor family and has been
      reported to be a marker of thymus-derived regulatory T cells (Treg). Helios is an
      intracellular protein, however, and hence cannot be used as a marker to separate
      living Tregs. To solve this problem, we generated Helios reporter mice in which
      Helios+ cells selectively express Venus, a variant of green fluorescent protein.
      Most of the Tregs in the thymus expressed Helios, whereas its expression was
      varied in peripheral lymphoid organs. The Helios+ Treg-population was superior in
      ability to suppress both antigen-specific and TCR-stimulated T cell responses. We
      also showed that Helios+ Tregs inhibited the cytokine production by T cells more
      efficiently than Helios- Tregs. We conclude that Helios reporter mouse strain is
      a useful tool to study function of Helios and that Helios+ Tregs represent the
      highly suppressive population. 

PMID- 25846705
TI  - The GO4KIDDS Brief Adaptive Scale.
AB  - BACKGROUND: Accurate measurement of adaptive behaviour is important in both
      clinical and research contexts. While several good clinical measures exist, as
      well as brief research measures for adults with intellectual disability, there is
      need for a brief and efficient measure for research with children and youth. We
      present preliminary psychometric properties of a new scale we developed for such
      purposes, the GO4KIDDS Brief Adaptive Behaviour Scale. MATERIALS AND METHODS: A
      large sample (n = 432) of parents of youth (aged 3-20) with intellectual
      disability and/or ASD completed an online survey that included the new scale. A
      subsample of these parents (n = 204) also completed the Scales of Independent
      Behavior-Revised Short Form (Scales of Independent Behavior-Revised Comprehensive
      Manual, 1996 and Riverside Publishing). RESULTS: The new scale has good internal
      consistency and correlates strongly with the Scales of Independent Behavior, thus
      supporting its reliability and validity. CONCLUSIONS: Although we do not
      recommend its use for clinical purposes, the GO4KIDDS Brief Adaptive Behaviour
      Scale may be useful for survey research with parents of children and youth with
      developmental disabilities.

PMID- 25846706
TI  - Overlap of Juvenile polyposis syndrome and Cowden syndrome due to de novo
      chromosome 10 deletion involving BMPR1A and PTEN: implications for treatment and
      surveillance.
AB  - We describe a patient with a severe juvenile polyposis phenotype, due to a de
      novo deletion of chromosome 10q22.3-q24.1. He was initially diagnosed with
      Juvenile polyposis syndrome (JPS) at age four after presenting with hematochezia
      due to multiple colonic juvenile polyps. He then re-presented at 23 years with
      recurrent hematochezia from juvenile polyps in his ileoanal pouch. He is one of
      the earliest reported cases of JPS associated with a large deletion of chromosome
      10. Since his initial diagnosis of JPS further studies have confirmed an
      association between JPS and mutations in BMPR1A in chromosome band 10q23.2, which
      is in close proximity to PTEN. Mutations in PTEN cause Cowden syndrome (CS) and
      other PTEN hamartoma tumor syndromes. Due to the chromosome 10 deletion involving
      contiguous portions of BMPR1A and PTEN in our patient, he may be at risk for CS
      associated cancers and features, in addition to the polyps associated with JPS.
      This case presents new challenges in developing appropriate surveillance
      algorithms to account for the risks associated with each syndrome and highlights
      the importance of longitudinal follow-up and transitional care between pediatric
      and adult gastroenterology for patients with hereditary polyposis syndromes.

PMID- 25846708
TI  - Validation of 1-year predictive score of long-term response to interferon-beta in
      everyday clinical practice multiple sclerosis patients.
AB  - BACKGROUND AND PURPOSE: The Rio score (RS) and the modified Rio score (MRS) are
      two scoring systems that can identify the early predictive factors of disability
      progression in relapsing-remitting multiple sclerosis (RRMS) patients treated
      with interferon-beta (IFN-beta). The objective of the study was to validate the
      usefulness of the RS and MRS in a large cohort of multiple sclerosis patients
      treated with IFN-beta in daily clinical practice. METHODS: The analysis included
      a cohort of RRMS patients treated with different formulations of IFN-beta for at
      least 1 year. The RS and MRS were used to classify the patients after 1 year of
      treatment. Multivariate analysis was performed to identify predictive variables
      of suboptimal response at 5 years, defined as Expanded Disability Status Scale
      confirmed progression or switching to a second-line therapy. RESULTS: Sixty-nine
      of 416 included patients were considered as suboptimal responders at 5-year
      evaluation. The possible score range was 0-3. A higher risk of suboptimal
      response was found for RS and MRS in the presence of >=2 scores (hazard ratio
      3.0, P = 0.002, and hazard ratio 5.0, P < 0.0001, respectively). CONCLUSIONS: Our
      study confirmed, in a daily clinical setting, that MRS had a better specificity
      and accuracy than RS in identifying the patients who will have a poor response to
      long-term IFN-beta treatment.

PMID- 25846707
TI  - Siglec receptors impact mammalian lifespan by modulating oxidative stress.
AB  - Aging is a multifactorial process that includes the lifelong accumulation of
      molecular damage, leading to age-related frailty, disability and disease, and
      eventually death. In this study, we report evidence of a significant correlation
      between the number of genes encoding the immunomodulatory CD33-related sialic
      acid-binding immunoglobulin-like receptors (CD33rSiglecs) and maximum lifespan in
      mammals. In keeping with this, we show that mice lacking Siglec-E, the main
      member of the CD33rSiglec family, exhibit reduced survival. Removal of Siglec-E
      causes the development of exaggerated signs of aging at the molecular,
      structural, and cognitive level. We found that accelerated aging was related both
      to an unbalanced ROS metabolism, and to a secondary impairment in detoxification
      of reactive molecules, ultimately leading to increased damage to cellular DNA,
      proteins, and lipids. Taken together, our data suggest that CD33rSiglecs co
      evolved in mammals to achieve a better management of oxidative stress during
      inflammation, which in turn reduces molecular damage and extends lifespan. 

PMID- 25846710
TI  - The Association Between Spontaneous Hyperventilation, Delayed Cerebral Ischemia,
      and Poor Neurological Outcome in Patients with Subarachnoid Hemorrhage.
AB  - BACKGROUND: The frequency and associations of spontaneous hyperventilation in
      subarachnoid hemorrhage (SAH) are unknown. Because hyperventilation decreases
      cerebral blood flow, it may exacerbate delayed cerebral ischemia (DCI) and worsen
      neurological outcome. METHODS: This is a retrospective analysis of data from a
      prospectively collected cohort of SAH patients at an academic medical center.
      Spontaneous hyperventilation was defined by PaCO2 <35 mmHg and pH >7.45 and
      subdivided into moderate and severe groups. Clinical and demographic
      characteristics of patients with and without spontaneous hyperventilation were
      compared using chi (2) or t tests. Bivariate and multivariable logistic
      regression analyses were conducted to examine the association of moderate and
      severe hyperventilation with DCI and discharge neurological outcome. RESULTS: Of
      207 patients, 113 (55 %) had spontaneous hyperventilation. Spontaneously
      hyperventilating patients had greater illness severity as measured by the Hunt
      Hess, World Federation of Neurosurgical Societies (WFNS), and SAH sum scores.
      They were also more likely to develop the following complications: pneumonia,
      neurogenic myocardial injury, systemic inflammatory response syndrome (SIRS),
      radiographic vasospasm, DCI, and poor neurological outcome. In a multivariable
      logistic regression model including age, gender, WFNS, SAH sum score, pneumonia,
      neurogenic myocardial injury, etiology, and SIRS, only moderate [odds ratio (OR)
      2.49, 95 % confidence interval (CI) 1.10-5.62] and severe (OR 3.12, 95 % CI 1.30
      7.49) spontaneous hyperventilation were associated with DCI. Severe spontaneous
      hyperventilation (OR 4.52, 95 % CI 1.37-14.89) was also significantly associated
      with poor discharge outcome in multivariable logistic regression analysis.
      CONCLUSION: Spontaneous hyperventilation is common in SAH and is associated with
      DCI and poor neurological outcome.

PMID- 25846709
TI  - Global monitoring in the neurocritical care unit.
AB  - Effective methods of monitoring the status of patients with neurological injuries
      began with non-invasive observations and evolved during the past several decades
      to include more invasive monitoring tools and physiologic measures. The
      monitoring paradigm continues to evolve, this time back toward the use of less
      invasive tools. In parallel, the science of monitoring began with the global
      assessment of the patient's neurological condition, evolved to focus on regional
      monitoring techniques, and with the advent of enhanced computing capabilities is
      now moving back to focus on global monitoring. The purpose of this session of the
      Second Neurocritical Care Research Conference was to collaboratively develop a
      comprehensive understanding of the state of the science for global brain
      monitoring and to identify research priorities for intracranial pressure
      monitoring, neuroimaging, and neuro-electrophysiology monitoring.

PMID- 25846712
TI  - High-intensity focused ultrasound treatment of placenta accreta after vaginal
      delivery: a preliminary study.
AB  - OBJECTIVE: To evaluate the safety and efficiency of high-intensity focused
      ultrasound (HIFU) in the treatment of placenta accreta after vaginal delivery.
      METHODS: Enrolled into this study between September 2011 and September 2013 were
      12 patients who had been diagnosed with placenta accreta following vaginal
      delivery and who had stable vital signs. All patients were treated using an
      ultrasound-guided HIFU treatment system. As indication of the effectiveness of
      the treatment we considered decreased vascular index on color Doppler imaging,
      decrease in size of residual placenta compared with pretreatment size on
      assessment by three-dimensional ultrasound with Virtual Organ Computer-aided
      Analysis, reduced signal intensity and degree of enhancement on magnetic
      resonance imaging and avoidance of hysterectomy following treatment. To assess
      the safety of HIFU treatment, we recorded side effects, hemorrhage, infection,
      sex steroid levels, return of menses and subsequent pregnancy. Patients were
      followed up in this preliminary study until December 2013. RESULTS: The 12
      patients receiving HIFU treatment had an average postpartum hospital stay of 6.8
      days and an average period of residual placental involution of 36.9 days. HIFU
      treatment did not apparently increase the risk of infection or hemorrhage and no
      patient required hysterectomy. In all patients menstruation recommenced after an
      average of 80.2 days, and sex steroid levels during the middle luteal phase of
      the second menstrual cycle were normal. Two patients became pregnant again during
      the follow-up period. CONCLUSION: This preliminary study suggests that ultrasound
      guided HIFU is a safe and effective non-invasive method to treat placenta accreta
      patients after vaginal delivery who have stable vital signs and desire to
      preserve fertility. Copyright (c) 2015 ISUOG. Published by John Wiley & Sons Ltd.

PMID- 25846713
TI  - Ammonium increases Ca(2+) signalling and upregulates expression of Cav1.2 gene in
      astrocytes in primary cultures and in the in vivo brain.
AB  - AIM: The primary aim of this study was to identify the effects of hyperammonaemia
      on functional expression of Cav1.2 L-type Ca(2+) channels in astroglia. METHODS:
      Primary cultures of mouse astrocytes were used to study effects of chronic
      treatment (1-5 days) with ammonium chloride, at 1, 3 and 5 mm on depolarization
      induced increases in free cytosolic Ca(2+) concentration ([Ca(2+)]i , measured
      with Fura-2 based microfluorimetry) in control conditions and following treatment
      with the L-type Ca(2+) channel inhibitor, nifedipine, or with ryanodine receptor
      inhibitor, ryanodine. Expression of Cav1.2 mRNA was identified with RT-PCR,
      whereas protein content was determined by Western blotting. Sustained
      hyperammonaemia in vivo was induced by daily injections of urease (33 units kg
      body weight(-1), i.p.) for 3 days. RESULTS: Depolarization-induced [Ca(2+)]i
      transients sensitive to nifedipine (peak of the response) and to ryanodine
      (plateau phase) were significantly increased in astrocytes chronically exposed to
      ammonium. The ammonium-induced increase in Ca(2+) influx in astrocytes resulted
      from an upregulation of Cav1.2 channel's expression detected at mRNA and protein
      levels. Increase in Cav1.2 expression was prevented by ouabain antagonist
      canrenone. Similar upregulation of Cav1.2 gene expression was found in the brains
      of adult mice subjected to intraperitoneal injection of urease. In transgenic
      mice tagged with an astrocyte-specific or neurone-specific markers and treated
      with intraperitoneal injections of urease, the fluorescence-activated cell
      sorting of neurones and astrocytes demonstrated that Cav1.2 mRNA expression was
      upregulated in astrocytes, but not in neurones. CONCLUSIONS: Ammonium-induced
      deregulation of astroglial Ca(2+) signalling, is, in part, associated with
      upregulation of Cav1.2 L-type calcium channels.

PMID- 25846711
TI  - Data collection and interpretation.
AB  - Patient monitoring is routinely performed in all patients who receive
      neurocritical care. The combined use of monitors, including the neurologic
      examination, laboratory analysis, imaging studies, and physiological parameters,
      is common in a platform called multi-modality monitoring (MMM). However, the full
      potential of MMM is only beginning to be realized since for the most part,
      decision making historically has focused on individual aspects of physiology in a
      largely threshold-based manner. The use of MMM now is being facilitated by the
      evolution of bio-informatics in critical care including developing techniques to
      acquire, store, retrieve, and display integrated data and new analytic techniques
      for optimal clinical decision making. In this review, we will discuss the crucial
      initial steps toward data and information management, which in this emerging era
      of data-intensive science is already shifting concepts of care for acute brain
      injury and has the potential to both reshape how we do research and enhance cost
      effective clinical care. 

PMID- 25846714
TI  - Association of TAP1 and TAP2 genes with susceptibility to pulmonary tuberculosis
      in Koreans.
AB  - Tuberculosis remains an important public health problem in Koreans. However, very
      few studies have reported on the genetic factors associated with TB
      susceptibility in Koreans. The aim of this study was to elucidate the genetic
      factors associated with susceptibility to pulmonary tuberculosis (PTB). We
      investigated the transporter associated with antigen processing -1 (TAP1) and
      TAP2 gene polymorphisms in 160 Korean PTB patients (categorized according to
      extent of lesion and TB medication history) and 210 controls. TAP2*C/E frequency
      was significantly increased in the PTB (pc = 0.004, OR = 2.28). TAP2*Bky2/C/E
      were enriched in the retreated, far-advanced and total PTB compared with the
      controls (pc = 0.015, OR = 3.27; pc = 0.019, OR = 2.56; pc = 2.8 * 10(-4) , OR =
      2.42, respectively). In the comparison of TAP2 gene with the DRB1*08:03, which is
      associated with TAP2*Bky2 and PTB in Koreans, we demonstrated the hierarchy of
      these association factors. TAP2*C/E is independent factors as strong as
      DRB1*08:03, and TAP2*C/E interacts with DRB1*08:03, resulting in a striking
      combined association. Our results suggest that TAP2 gene has an association with
      PTB susceptibility, the extent of the lesion or recurrence. These associations
      are independent from and additive with DRB1*08:03.

PMID- 25846715
TI  - Associations between sensation seeking and d-amphetamine reinforcement.
AB  - BACKGROUND AND OBJECTIVES: While many individuals experiment with stimulants,
      only a subset transition to abuse or dependence. One characteristic widely
      associated with stimulant abuse vulnerability in general is sensation seeking
      (SS), though less clear is how individuals' baseline SS may predict their
      response to acute stimulant administration. METHODS: In this secondary analysis,
      we examined associations between SS and d-AMPH choice and subjective response
      among healthy male (n = 16) and female (n = 21) adults participating in an
      outpatient laboratory study wherein they received repeated opportunities to
      sample and choose between d-AMPH (5, 10, and 20 mg/70 kg) and placebo. RESULTS:
      Among males, elevated baseline SS was associated with increased d-AMPH choice and
      positive subjective effects at 5 and 10 mg/70 kg doses. Among females, there were
      no significant associations between SS and d-AMPH choice or subjective effects.
      DISCUSSION AND CONCLUSIONS: Elevated SS in males may be associated with increased
      sensitivity to d-AMPH reinforcement and positive subjective effects. Data from
      this study suggest that SS may not predict sensitivity to stimulants in females,
      though future studies with larger sample sizes are necessary to answer this
      definitively. SCIENTIFIC SIGNIFICANCE: Sensation seeking may reflect an important
      characteristic underlying sensitivity to stimulant reinforcement. Efforts to
      better understand these individual differences would inform efforts to identify
      and intervene with those at risk for developing abuse or dependence.

PMID- 25846716
TI  - Clinical presentation of human C1q deficiency: How much of a lupus?
AB  - Hereditary human C1q deficiency has been well described to be associated with
      high susceptibility for the development of systemic lupus erythematosus (SLE).
      The majority of subjects present a clinical syndrome closely related to SLE.
      However, limited information is available about the primary diagnosis and
      particular clinical manifestations of SLE in this specific subgroup of patients.
      In this review, we performed a comprehensive search of electronic databases up to
      November 2014 to identify and analyze reports on patients with C1q deficiency. We
      identified 71 C1q-deficient patients descending from 45 families that had been
      published. According to the American College of Rheumatology (ACR) diagnostic
      criteria for SLE 39/71 (55%) subjects could be classified as having SLE. Another
      16/71 (22.5%) presented a SLE-like syndrome (defined as 3 positive ACR criteria)
      whereas in 16/71 (22.5%) no SLE could be diagnosed at time of publication.
      Symptoms began at a median age of 5 years, male and females being equally
      affected. Discoid rash (56% versus 10%, p<0.001) and oral ulcers (49% versus 24%,
      p<0.001) occurred significantly more frequent in C1q deficiency-associated
      SLE/SLE-like disease than in sporadic SLE, whereas arthritis (38% versus 84%,
      p<001) and anti-ds-DNA (18% versus 78%, p<0.001) occurred less frequently. Renal
      and neurological manifestations were found to occur similarly frequent. The
      severe course of disease in some patients seemed to be mostly due to severe
      infections at early ages and not in particular due to more aggressive SLE
      manifestations. 

PMID- 25846717
TI  - Dressed to impress: impact of environmental adaptation on the Candida albicans
      cell wall.
AB  - Candida albicans is an opportunistic fungal pathogen of humans causing
      superficial mucosal infections and life-threatening systemic disease. The fungal
      cell wall is the first point of contact between the invading pathogen and the
      host innate immune system. As a result, the polysaccharides that comprise the
      cell wall act as pathogen associated molecular patterns, which govern the host
      pathogen interaction. The cell wall is dynamic and responsive to changes in the
      external environment. Therefore, the host environment plays a critical role in
      regulating the host-pathogen interaction through modulation of the fungal cell
      wall. This review focuses on how environmental adaptation modulates the cell wall
      structure and composition, and the subsequent impact this has on the innate
      immune recognition of C. albicans. 

PMID- 25846719
TI  - Gut microbiome composition and metabolomic profiles of wild western lowland
      gorillas (Gorilla gorilla gorilla) reflect host ecology.
AB  - The metabolic activities of gut microbes significantly influence host physiology;
      thus, characterizing the forces that modulate this micro-ecosystem is key to
      understanding mammalian biology and fitness. To investigate the gut microbiome of
      wild primates and determine how these microbial communities respond to the host's
      external environment, we characterized faecal bacterial communities and, for the
      first time, gut metabolomes of four wild lowland gorilla groups in the Dzanga
      Sangha Protected Areas, Central African Republic. Results show that geographical
      range may be an important modulator of the gut microbiomes and metabolomes of
      these gorilla groups. Distinctions seemed to relate to feeding behaviour,
      implying energy harvest through increased fruit consumption or fermentation of
      highly fibrous foods. These observations were supported by differential abundance
      of metabolites and bacterial taxa associated with the metabolism of cellulose,
      phenolics, organic acids, simple sugars, lipids and sterols between gorillas
      occupying different geographical ranges. Additionally, the gut microbiomes of a
      gorilla group under increased anthropogenic pressure could always be
      distinguished from that of all other groups. By characterizing the interplay
      between environment, behaviour, diet and symbiotic gut microbes, we present an
      alternative perspective on primate ecology and on the forces that shape the gut
      microbiomes of wild primates from an evolutionary context.

PMID- 25846718
TI  - Essential Role of Interleukin-12/23p40 in the Development of Graft-versus-Host
      Disease in Mice.
AB  - Graft-versus-host disease (GVHD), in both its acute (aGVHD) and chronic (cGVHD)
      forms, remains a major obstacle impeding successful allogeneic hematopoietic stem
      cell transplantation (allo-HSCT). T cells, in particular pathogenic T helper (Th)
      1 and Th17 subsets, are a driving force for the induction of GVHD. IL-12 and IL
      23 cytokines share a common p40 subunit and play a critical role in driving Th1
      differentiation and in stabilizing the Th17 phenotype, respectively. In our
      current study, we hypothesized that p40 is an essential cytokine in the
      development of GVHD. By using p40-deficient mice, we found that both donor- and
      host-derived p40 contribute to the development of aGVHD. Neutralization of p40
      with an anti-p40 mAb inhibited Th1- and Th17-polarization in vitro. Furthermore,
      anti-p40 treatment reduced aGVHD severity while preserving the graft-versus
      leukemia (GVL) activity. Alleviation of aGVHD was associated with an increase of
      Th2 differentiation and a decrease of Th1 and Th17 effector T cells in the GVHD
      target organs. In addition, anti-p40 treatment attenuated the severity of
      sclerodermatous cGVHD. These results provide a strong rationale that blockade of
      p40 may represent a promising therapeutic strategy in preventing and treating
      aGVHD and cGVHD while sparing the GVL effect after allo-HSCT. 

PMID- 25846720
TI  - Mechanical suction for clot evacuation: experience with "suction bridge" for safe
      and effective clot removal.
AB  - OBJECTIVES: To present the experience with the use of a "suction bridge" for
      removal of bladder clots. METHODS: In all patients presenting with bladder clots,
      mechanical suction was done using a "suction bridge". This bridge has a luer lock
      that is fixed to the cystoscope sheath, and the other end is connected to suction
      tube. The suction pressure was started at 250 mmHg and was increased up to 400
      mmHg if needed. RESULTS: Twenty patients with a mean age of 59.4 years were
      included. The etiologies of bladder clots included bladder tumor in nine, benign
      prostate hyperplasia (BPH) in two, BPH with bladder stone in one, hematochyluria
      in three, and post-transurethral prostate resection in 10. Eighteen patients
      presented in clot retention. The estimated clot size ranged from 50 mL to more
      than 1 L. The mean duration for clot removal was 15 min (range 5-60). The
      procedure was successful in all patients. There was no bladder injury. The
      limitations include the small number of recruits, the non-randomized nature of
      study, and no control group for comparison. CONCLUSION: Mechanical suction is
      another safe, fast, and effective option of clot removal from the urinary
      bladder. The suction bridge is useful while using this method.

PMID- 25846722
TI  - Synthesis, characterization and antimicrobial activity of water-soluble silver(i)
      complexes of metronidazole drug and selected counter-ions.
AB  - A series of water-soluble silver(i) complexes of the type [Ag(MTZ)2X] [MTZ = 1-(2
      hydroxyethyl)-2-methyl-5-nitro-1H-imidazole (metronidazole drug); X = NO3(-),
      ClO4(-), CF3COO(-), BF4(-) and CH3SO3(-)] was synthesised by the reactions of
      various Ag(i) salts with metronidazole (MTZ). All the complexes were
      characterized by ESI-MS spectrometry, solution NMR ((1)H and (13)C) and IR
      spectroscopy, and elemental analysis. Further evidence for the formation and
      molecular structure of all the complexes was provided by X-ray single-crystal
      crystallography. The different counter ions affect the crystal packing of the
      complexes and thus have an impact on the final geometries. The antimicrobial
      activities of the complexes against two Gram-positive strains: Staphylococcus
      aureus ATCC 6538, Staphylococcus epidermidis ATCC 12228, three Gram-negative
      strains: Pseudomonas aeruginosa ATCC 15442, Escherichia coli ATCC 25922, Proteus
      hauseri ATCC 13315 and yeast Candida albicans ATCC 10231 were evaluated and
      compared with antibacterial and antifungal properties of appropriate silver
      salts, metronidazole and silver sulfadiazine drugs. The newly synthesized
      compounds exhibited significant antibacterial activity against Gram-positive
      bacteria, better than the referenced silver sulfadiazine. The best active
      silver(i)-metronidazole complex contains a methanesulphonate counter-ion.
      Moreover, the complex inhibited the growth of yeast Candida albicans at a
      concentration 3-fold lower than that required for silver sulfadiazine. In
      addition, the complexes containing a tetrafluoroborate and a perchlorate as
      counter-ions were characterized as effective antibacterial agents against the
      tested Gram-negative bacteria. 

PMID- 25846721
TI  - One-year sustained glycaemic control and less hypoglycaemia with new insulin
      glargine 300 U/ml compared with 100 U/ml in people with type 2 diabetes using
      basal plus meal-time insulin: the EDITION 1 12-month randomized trial, including
      6-month extension.
AB  - AIMS: To evaluate the maintenance of efficacy and safety of insulin glargine 300
      U/ml (Gla-300) versus glargine 100 U/ml (Gla-100) in people with type 2 diabetes
      mellitus (T2DM) using basal plus meal-time insulin for 12 months in the EDITION 1
      trial. METHODS: EDITION 1 was a multicentre, randomized, open-label, two-arm,
      phase IIIa study. Participants completing the initial 6-month treatment period
      continued to receive Gla-300 or Gla-100, as previously randomized, once daily for
      a further 6-month open-label extension phase. Changes in glycated haemoglobin
      (HbA1c) and fasting plasma glucose concentrations, insulin dose, hypoglycaemic
      events and body weight were assessed. RESULTS: Of 807 participants enrolled in
      the initial phase, 89% (359/404) assigned to Gla-300 and 88% (355/403) assigned
      to Gla-100 completed 12 months. Glycaemic control was sustained in both groups
      (mean HbA1c: Gla-300, 7.24%; Gla-100, 7.42%), with more sustained HbA1c reduction
      for Gla-300 at 12 months: least squares mean difference Gla-300 vs Gla-100: HbA1c
      -0.17 [95% confidence interval (CI) -0.30 to -0.05]%. The mean daily basal
      insulin dose at 12 months was 1.03 U/kg for Gla-300 and 0.90 U/kg for Gla-100.
      Lower percentages of participants had >=1 confirmed [<=3.9 mmol/l (<=70 mg/dl)]
      or severe hypoglycaemic event with Gla-300 than Gla-100 at any time of day [24 h;
      86 vs 92%; relative risk 0.94 (95% CI 0.89-0.99)] and during the night [54 vs
      65%; relative risk 0.84 (95% CI 0.75-0.94)], while the annualized rates of such
      hypoglycaemic events were similar. No between-treatment differences in adverse
      events were apparent. CONCLUSION: During 12 months of treatment of T2DM requiring
      basal and meal-time insulin, glycaemic control was better sustained and fewer
      individuals reported hypoglycaemia with Gla-300 than with Gla-100. The mean basal
      insulin dose was higher with Gla-300 compared with Gla-100, but total numbers of
      hypoglycaemic events and overall tolerability did not differ between treatments.

PMID- 25846723
TI  - Connecting nursing leadership and patient outcomes: state of the science.

PMID- 25846725
TI  - Wellness among US adolescents ages 12-17 years.
AB  - BACKGROUND: Wellness is a multidimensional construct related to an individual's
      physical, emotional, intellectual and social well-being. We present estimates of
      wellness among US adolescents aged 12-17 years and explore how demographic
      characteristics are associated with wellness. METHODS: All respondents aged 12 to
      17 years (n = 34,601) from the 2011-2012 National Survey of Children's Health
      were included in the sample. Survey items were coded to operationalize an overall
      wellness score, comprised of four subdimensions (physical, intellectual,
      emotional and social). RESULTS: The mean adjusted overall wellness score was 30.2
      (out of 40). Mean raw subdimensions scores were: social = 3.14 (out of 4),
      emotional = 4.79 (out of 6), intellectual = 4.80 (out of 8) and physical = 6.57
      (out of 8). Older adolescents, those with special health needs, those in lower
      income families and those whose mother or father report fair-poor mental health
      status had lower wellness scores. CONCLUSIONS: US adolescents have wellness
      scores towards the upper or higher end of our scale. Several adolescent and
      family characteristics were associated with either lower overall wellness and/or
      lower wellness on multiple subdimensions. Assessing wellness during critical
      developmental periods of adolescence is a first step towards promoting behaviours
      that support increased wellness into adulthood.

PMID- 25846724
TI  - Lovastatin-Mediated Changes in Human Tendon Cells.
AB  - Statins are among the most widely prescribed drugs worldwide. Numerous studies
      have shown their beneficial effects in prevention of cardiovascular disease
      through cholesterol-lowering and anti-atherosclerotic properties. Although some
      statin patients may experience muscle-related symptoms, severe side effects of
      statin therapy are rare, primarily due to extensive first-pass metabolism in the
      liver. Skeletal muscles appear to be the main site of side effects; however,
      recently some statin-related adverse effects have been described in tendon. The
      mechanism behind these side effects remains unknown. This is the first study that
      explores tendon-specific effects of statins in human primary tenocytes. The cells
      were cultured with different concentrations of lovastatin for up to 1 week. No
      changes in cell viability or morphology were observed in tenocytes incubated with
      therapeutic doses. Short-term exposure to lovastatin concentrations outside the
      therapeutic range had no effect on tenocyte viability; however, cell migration
      was reduced. Simvastatin and atorvastatin, two other drug family members, also
      reduced the migratory properties of the cells. Prolonged exposure to high
      concentrations of lovastatin induced changes in cytoskeleton leading to cell
      rounding and decreased levels of mRNA for matrix proteins, but increased BMP-2
      expression. Gap junctional communication was impaired but due to cell shape
      change and separation rather than direct gap junction inhibition. These effects
      were accompanied by inhibition of prenylation of Rap1a small GTPase.
      Collectively, we showed that statins in a dose-dependent manner decrease
      migration of human tendon cells, alter their expression profile and impair the
      functional network, but do not inhibit gap junction function.

PMID- 25846726
TI  - Prehospital care and transportation of pediatric trauma patients.
AB  - BACKGROUND: Despite advances in prehospital emergency medical services (EMS),
      most advocate "scoop-and-run" over "stay-and-play." However, there are almost no
      studies in children. We hypothesize that the transportation of mortally injured
      children is delayed and that the performance of prehospital interventions (PHIs)
      themselves delay transportation and worsen outcomes in pediatric trauma patients.
      MATERIALS AND METHODS: A total of 1884 admissions (<=17-y-old) transported via
      EMS to a level 1 trauma center from January 2000-December 2012 were reviewed.
      Propensity scores were assigned based on the need for a PHI (intubation and
      resuscitation). PHI and non-PHI cohorts were matched 1:1 to compare outcomes.
      Data are expressed as mean +/- standard deviation or median (interquartile
      range). RESULTS: The population was 11 +/- 6 y, 70% male, 50% black, 76% blunt
      injury, injury severity score 13 +/- 12, length of stay 3 (7) d, and mortality
      3.6%. Incident to EMS arrival was 38 (20) min, EMS on-scene time was 14 (12) min,
      and overall time of arrival to hospital was 27 (15) min. Patients that were
      mortally wounded, despite having significantly higher rates of PHI, still had
      similar transportation times to those who survived. Mostly every measure of
      injury severity was worse in those who required PHI. When these factors were
      corrected, EMS on-scene time was 18 (13) versus 14 (13) min (P = 0.551), EMS
      arrival at the hospital was 31 (16) versus 28 (12) min (P = 0.292), length of
      stay was 5 (15) versus 4 (12) d (P = 0.368), and mortality was 31.7% versus 28.3%
      (P = 0.842) for PHI and non-PHI matched cohorts. CONCLUSIONS: PHIs did not delay
      transportation times or worsen outcomes in pediatric trauma patients. Although
      mortally injured children more often required PHIs, this did not delay
      transportation to the trauma center.

PMID- 25846727
TI  - p85alpha is a microRNA target and affects chemosensitivity in pancreatic cancer.
AB  - BACKGROUND: We previously identified a correlation between increased expression
      of the phosphoinositide 3-kinase (PI3K) regulatory subunit p85alpha and improved
      survival in human pancreatic ductal adenocarcinoma (PDAC). The purpose of this
      study was to investigate the impact of changes in p85alpha expression on response
      to chemotherapy and the regulation of p85alpha by microRNA-21 (miR-21). MATERIALS
      AND METHODS: PDAC tumor cells overexpressing p85alpha were generated by viral
      transduction, and the effect of p85alpha overexpression on sensitivity to
      gemcitabine was tested by MTT assay. Primary human PDAC tumors were stained for
      p85alpha and miR-21 via immunohistochemistry and in situ hybridization,
      respectively. Additionally, PDAC cells were treated with miR-21 mimic, and
      changes in p85alpha and phospho-AKT were assessed by Western blot. Finally, a
      luciferase reporter assay system was used to test direct regulation of p85alpha
      by miR-21. RESULTS: Higher p85alpha expression resulted in increased sensitivity
      to gemcitabine (P < 0.01), which correlated with decreased PI3K-AKT activation.
      Human tumors demonstrated an inverse correlation between miR-21 and p85alpha
      expression levels (r = -0.353, P < 0.001). In vitro, overexpression of miR-21
      resulted in decreased levels of p85alpha and increased phosphorylation of AKT.
      Luciferase reporter assays confirmed the direct regulation of p85alpha by miR-21
      (P < 0.01). CONCLUSIONS: Our results demonstrate that p85alpha expression is a
      determinant of chemosensitivity in PDAC. Additionally, we provide novel evidence
      that miR-21 can influence PI3K-AKT signaling via its direct regulation of
      p85alpha. These data provide insight into potential mechanisms for the known
      relationship between increased p85alpha expression and improved survival in PDAC.

PMID- 25846728
TI  - Microparticles impact coagulation after traumatic brain injury.
AB  - BACKGROUND: The pathophysiology that drives the subacute hypercoagulable state
      commonly seen after traumatic brain injury (TBI) is not well understood.
      Alterations caused by TBI in platelet and microparticle (MP) numbers and function
      have been suggested as possible causes; however, the contributions of platelets
      and MPs are currently unknown. MATERIALS AND METHODS: A weight-drop technique of
      TBI using a murine model of moderate head injury was used. Blood was collected at
      intervals after injury. MP enumeration and characterization were performed using
      Nanoparticle Tracking Analysis, and platelet counts and coagulation parameters
      were determined using thromboelastometry. A MP procoagulant assay was used to
      compare activity between injured and sham mice. RESULTS: At 24 h after injury,
      there were no changes in circulating platelet numbers. However, there was a
      decrease in platelet contribution to clot formation. In contrast, there was a
      decline in circulating total MP numbers. When MPs from sham mice were added to
      the blood from head-injured animals, there was a normalization of platelet
      contribution to clot formation. Conversely, when MPs from TBI mice were added to
      sham blood, there was a significant decrease in platelet contribution to clot
      formation. Notably, there was an increase in MP procoagulant activity in head
      injured mice. CONCLUSIONS: MPs generated after TBI likely contribute to altered
      coagulation after head injury and may play a key role in the development of a
      posttraumatic hypercoagulable state in TBI patients.

PMID- 25846729
TI  - Concentrations of retinol and tocopherols in the milk of cows supplemented with
      conjugated linoleic acid.
AB  - This study was performed to investigate the hypothesis that supplementation of
      conjugated linoleic acid (CLA) changes the concentrations of retinol and
      tocopherols in the milk of cows. To investigate this hypothesis, Holstein cows
      received daily from 3 weeks ante-partum to 14 weeks post-partum either 172 g of a
      CLA-free rumen-protected control fat (control group, n = 20) or the same amount
      of a rumen-protected CLA fat, supplying 4.3 g of cis-9, trans-11 CLA and 3.8 g of
      trans-10, cis-12 CLA per d (CLA group, n = 20). Milk samples (collected at weeks
      1, 3, 5, 8 and 11 of lactation) were analysed for retinol, alpha- and gamma
      tocopherol concentrations. Milk of cows supplemented with CLA had higher
      concentrations of retinol (+34%), alpha-tocopherol (+44%) and gamma-tocopherol
      (+21%) than milk of control cows (p < 0.05). The daily output of these vitamins
      via milk was also greater in cows of the CLA group than in cows of the control
      group (+36, 50 and 24% for retinol, alpha-tocopherol and gamma-tocopherol,
      respectively, p < 0.05). In agreement with higher concentrations of tocopherols,
      concentrations of thiobarbituric acid-reactive substances, determined in milk of
      week 5, were lower in cows of the CLA group than in control cows, indicative of a
      lower susceptibility of milk lipids to peroxidation. Plasma concentrations of
      retinol and alpha-tocopherol, determined at 1 and 5 weeks post-partum, were not
      different between the two groups of cows. In conclusion, this study shows that
      supplementing dairy cows with a moderate amount of CLA causes an increase of the
      concentrations of vitamins A and E in the milk and results in an increased output
      of those vitamins via milk. These effects might be beneficial with respect to the
      nutritional value of dairy products and the susceptibility of milk fat to
      oxidative deterioration.

PMID- 25846730
TI  - Australian hip surveillance guidelines for children with cerebral palsy: 5-year
      review.
AB  - AIM: To ensure hip surveillance guidelines reflect current evidence of factors
      influencing hip displacement in children with cerebral palsy (CP). METHOD: A
      three-step review process was undertaken: (1) systematic literature review, (2)
      analysis of hip surveillance databases, and (3) national survey of orthopaedic
      surgeons managing hip displacement in children with CP. RESULTS: Fifteen articles
      were included in the systematic review. Quantitative analysis was not possible.
      Qualitative review indicated hip surveillance programmes have decreased the
      incidence of hip dislocation in populations with CP. The Gross Motor Function
      Classification System was confirmed as the best indicator of risk for
      displacement, and evidence was found of hip displacement occurring at younger
      ages and in young adulthood. Femoral geometry, pelvic obliquity, and scoliosis
      were linked to progression of hip displacement. A combined data pool of 3366
      children from Australian hip surveillance databases supported the effectiveness
      of the 2008 Consensus Statement to identify hip displacement early. The survey of
      orthopaedic surgeons supported findings of the systematic review and database
      analyses. INTERPRETATION: This review rationalized changes to the revised and
      renamed Australian Hip Surveillance Guidelines for Children with Cerebral Palsy
      2014, informing frequency of radiographic examination in lower risk groups and
      continuation of surveillance into adulthood for adolescents with identified risk
      factors.

PMID- 25846731
TI  - MicroRNA-506 inhibits gastric cancer proliferation and invasion by directly
      targeting Yap1.
AB  - Increasing evidence indicates that microRNA (miR)-506 plays a vital role in
      tumorigenesis; however, the role of miR-506 in gastric cancer (GC) is unclear and
      needs further investigation. In the present study, we showed that the decrease in
      the expression of miR-506 is associated with tumor size, pathological tumor node
      metastasis (TNM) stage, and lymph node metastasis in 63 GC patient tumors. We
      found that patients with lower expression of miR-506 had a poor prognosis than
      that with the patients with high expression of miR-506. Notably, the ectopic
      expression of miR-506 was sufficient to inhibit cell proliferation, invasion, and
      epithelial-mesenchymal transition in the GC cells. Moreover, results from
      luciferase reporter assays identified miR-506 as a direct regulator of Yes
      associated protein 1 (Yap1). Reintroduction of Yap1 rescues miR-506-induced
      effects on SGC-7901 cell proliferation and invasion. This function of miR
      506/Yap1 axis is clinically significant, as the level of miR-506 is inversely
      correlated with Yap1 mRNA expression in matched tissues. Thus, our study
      demonstrates that miR-506 may act as a tumor suppressor in GC and that the miR
      506/Yap1 axis may help us better understand the molecular mechanisms of GC
      progression.

PMID- 25846732
TI  - The M30 assay does not detect apoptosis in epithelial-derived cancer cells
      expressing low levels of cytokeratin 18.
AB  - The primary aim of this study was to compare measurement of apoptosis by M30
      immunoreactivity (a biomarker for apoptosis) to other apoptosis assays
      (morphological assessment of nuclei, Annexin-V-FITC staining, DNA fragmentation
      and PARP cleavage) in vitro. Caspase-cleaved cytokeratin 18 (M30, ccK18) is only
      produced in epithelial cells and is regarded as a pharmacodynamic biomarker of
      apoptotic cell death because it is released from cells during apoptosis induced
      by chemotherapeutic agents. However, we have observed false negative results
      using this assay in clinical samples. Therefore, we tested its ability to
      accurately detect apoptosis in a panel of lung cancer cell lines with a range of
      clinically approved chemotherapeutic drugs. Three different non-small cell lung
      cancer (NSCLC) cell lines (A549, H1299, PC3) were used to correlate M30 levels
      with alternate apoptosis assays. Following successful induction of apoptosis, the
      A549 cell line showed an increase in M30 levels along with other well-known
      features of apoptosis, whilst H1299 and PC3 cell lines did not show an increase
      in M30 levels, even when apoptosis was detected by other means. Further analysis
      showed that H1299 and PC3 cell lines expressed much lower levels of cytokeratin
      18 protein compared to the A549 cell line. Our results suggest that reliable
      detection of apoptosis via the M30 assay only works when sufficient levels of
      cytokeratin 18 are present in the cells. This means that the M30 assay may result
      in false negative results for apoptosis, and as such, the ELISA should be used in
      conjunction with other assays.

PMID- 25846733
TI  - ObRb downregulation increases breast cancer cell sensitivity to tamoxifen.
AB  - Leptin is a potent adipokine that plays an important role in the progression of
      breast cancer and interferes with the action of tamoxifen. We investigated the
      molecular mechanism underlying the effect of leptin on tamoxifen resistance in
      breast cancer cells that express leptin receptor (ObRb), and evaluated the impact
      of ObRb suppression on tamoxifen treatment in MCF-7 and tamoxifen-resistant (TAM
      R) cells. Leptin-induced signaling pathway activation was examined by qRT-PCR and
      Western blotting. Chromatin immunoprecipitation assays were performed to further
      examine the binding of estrogen receptor (ER) alpha on the promoter of cyclin D1
      (CCND1) gene. The effects of combined ObRb knockdown and tamoxifen treatment were
      evaluated in MCF-7 and TAM-R cells. We found that the enhanced proliferation
      effects induced by leptin were related to extracellular-signal-regulated kinase
      (ERK) 1/2 and signal transducers and activators of transcription (STAT) 3
      signaling pathway activation and CCND1 upregulation. Leptin enhanced CCND1 gene
      transcription by inducing the binding of ERalpha to the promoter of CCND1 gene.
      ObRb knockdown significantly enhanced the inhibitory effects of tamoxifen on TAM
      R cell proliferation and survival. This study suggested that long-term endocrine
      therapy facilitates leptin and ObRb overexpression in breast cancer cells, which
      attenuates the inhibitory effect of tamoxifen by activating both the ERK1/2 and
      STAT3 signaling pathways and upregulating CCND1 gene expression. Combination
      therapy involving ObRb knockdown and tamoxifen treatment may be an alternative
      therapeutic option for tamoxifen-resistant breast cancer.

PMID- 25846734
TI  - miR-335 inhibits the proliferation and invasion of clear cell renal cell
      carcinoma cells through direct suppression of BCL-W.
AB  - Increasing evidence has demonstrated that small non-coding microRNAs (miRNAs)
      play important roles in cancer development and progression. Recent studies have
      shown that microRNA-335 (miR-335) functions as an oncogene or a tumor suppressor
      in various human cancer types, but its role in clear cell renal cell carcinoma
      (ccRCC) remains poorly understood. In our study, we firstly found that the
      expression level of miR-335 was significantly downregulated in ccRCC tissues
      versus corresponding non-tumor tissues and the low expression of miR-335 was
      significantly associated with lymph node metastasis, larger tumor size, and poor
      T stage. Then, we found that overexpression of miR-335 significantly suppressed
      the proliferation and invasion of 786-O and CaKi-1 ccRCC cell lines. We
      subsequently found that miR-335 could interact with the 3'-untranslated regions
      (3'UTR) of B-cell CLL/lymphoma 2 like 2 (BCL-W or BCL2L2) messenger RNA (mRNA)
      and repress its expression. In addition, re-expression of BCL-W (without the
      3'UTR) could partially abrogate the miR-335-induced 786-O and CaKi-1 ccRCC cell
      proliferation and invasion inhibition. Furthermore, we found that expression
      patterns of miR-335 were inversely correlated with those of BCL-W mRNA in ccRCC
      tissues. Taken together, these results indicate that miR-335 acts as a novel
      tumor suppressor to regulate ccRCC cell proliferation and invasion through
      downregulation of BCL-W expression.

PMID- 25846735
TI  - Clinical significance of topoisomerase 2A expression and gene change in operable
      invasive breast cancer.
AB  - This study aims to investigate clinical significance of topoisomerase 2A (TOP2A)
      expression and TOP2A gene change in operable invasive breast cancer. This is a
      retrospective analysis, which includes 256 patients diagnosed as operable
      invasive breast cancer. All postoperational waxed specimens were subjected to
      resectioning for staining. Estrogen receptor (ER), progesterone receptor (PR),
      human epidermal growth factor receptor 2 (HER-2), KI-67, TOP2A expression, and
      TOP2A gene changes were detected by immunohistochemistry (IHC) and fluorescent in
      situ hybridization technique (FISH), respectively. Correlation between TOP2A
      expression and clinicopathological characteristics was also investigated. Effects
      of TOP2A protein or gene changes on survival rate were detected. Results
      indicated that 165 were TOP2A positive (64.5 %), and 31 were gene amplification
      positive (12.1 %). Positive rate of TOP2A expression showed significant
      correlations with ER, KI-67, and HER-2. The difference of 5-year overall survival
      (OS) between TOP2A-positive and TOP2A-negative groups did not reach statistical
      significance (OS: P = 0.321, 85.9 vs. 79.6 %; disease-free survival [DFS]: P =
      0.247, 83.3 vs. 75.3 %). Five-year OS in TOP2A amplification group was 68.8 %,
      which is lower than deficiency and control group (P > 0.05). Subgroup analysis
      showed no significant differences of OS and DFS either between TOP2A-positive and
      TOP2A-negative groups or between TOP2A amplification and control group in
      population of patients with HER-2 amplification, triple negative breast cancer,
      or hormone-positive breast cancer. In conclusion, positive rate of TOP2A
      expression correlates significantly with ER, KI-67, and HER-2. However,
      prognostic significance of either TOP2A expression or TOP2A gene changes in
      breast cancer and its various subtypes is limited.

PMID- 25846737
TI  - Antitumor activity of photodynamic therapy with a chlorin derivative in vitro and
      in vivo.
AB  - Chlorin derivatives are promising photosensitive agents for photodynamic therapy
      (PDT) of tumors. The aim of the current study is to investigate the PDT
      therapeutic effects of a novel chlorin-based photosensitizer, meso-tetra[3-(N,N
      diethyl)aminomethyl-4-methoxy]phenyl chlorin (TMPC) for gliomas in vitro and in
      vivo. Physicochemical characteristics of TMPC were recorded by ultraviolet
      visible spectrophotometer and fluorescence spectrometer. The rate of singlet
      oxygen generation of TMPC upon photo-excitation was detected by using 1,3
      diphenylisobenzofuran (DPBF). The accumulation of TMPC in gliomas U87 MG cells
      was measured by fluorescence spectrometer. The efficiency of TMPC-PDT in vitro
      was analyzed by MTT assay and clonogenic assay. The biodistribution and clearance
      of TMPC were determined by fluorescence measuring. Human gliomas U87 MG tumor
      bearing mice model was used to evaluate the antitumor effects of TMPC-PDT. TMPC
      shows a singlet oxygen generation rate of 0.05 and displays a characteristic long
      wavelength absorption peak at 653 nm (epsilon = 15,400). The accumulation of TMPC
      increased with the increase of incubation time. In vitro, PDT using TMPC and
      laser showed laser dose- and concentration-dependent cytotoxicity to U87 MG
      cells. In U87 MG tumor-bearing mice, TMPC-PDT significantly reduced the growth of
      the tumors. Both in vitro and in vivo, TMPC showed little dark toxicity. In vitro
      and in vivo studies, it found that TMPC has excellent antitumor activities. It
      suggests that TMPC is a potential photosensitizer of photodynamic therapy for
      cancer.

PMID- 25846736
TI  - Clinical significance and biological roles of TRIM24 in human bladder carcinoma.
AB  - Tripartite motif-containing 24 (TRIM24), also known as transcription intermediary
      factor 1-alpha (TIF1alpha), is a chromatin-associated protein which as been has
      been implicated in carcinogenesis. However, its expression profile and biological
      roles in human bladder carcinoma has not been investigated. In this study, we
      examined its expression in 95 bladder cancer specimens. We found that TRIM24
      expression was upregulated in 39 of 95 (41.1 %) specimens compared with normal
      control. TRIM24 overexpression was associated with local invasion and advanced
      grade of bladder cancer. In addition, we transfected TRIM24 plasmid into BIU-87
      cell line and TRIM24 siRNA into 5637 cell line. Colony formation, CCK-8, and
      transwell assay were used to assess its biological roles in bladder cancer cells.
      The result showed that TRIM24 could facilitate cancer cell growth and invading
      ability. Western blot analysis demonstrated that TRIM24 upregulated cyclin D1,
      cyclin E, p-IkappaBalpha, and p-AKT expression, suggesting TRIM24 activates NF
      kappaB and AKT pathways. In addition, NF-kappaB inhibitor reversed the effect of
      TRIM24 on cyclin D1. In conclusion, TRIM24 is overexpressed in human bladder
      cancer and facilitates bladder cancer growth and invasion, possibly through NF
      kappaB and AKT signaling pathways.

PMID- 25846738
TI  - MicroRNA-9 promotes tumorigenesis and mediates sensitivity to cisplatin in
      primary epithelial ovarian cancer cells.
AB  - MicroRNAs play critical roles in regulating tumor occurrence and drug sensitivity
      in ovarian cancers. This study aimed to investigate the key members of MicroRNAs
      (miRNAs) involved in modulating tumor initiation and drug resistance in primary
      ovarian cancer cells. An in vitro assay based on tumor clonal formation was
      established to evaluate tumorigenicity and cisplatin sensitivity. By performing
      real-time polymerase chain reaction, we examined the expression of nine microRNAs
      associated with the pathology of ovarian cancers in primary ovarian tumor cells,
      which were surgically resected from 46 patients with distinct sensitivity to
      platinum-based chemotherapy. MiR-9, miR-145, and miR-429 were expressed
      significantly higher in drug-sensitive patients (n = 26) than in drug-resistant
      ones (n = 20), while higher miR-26a expression was found in resistant patients (p
      < 0.05). In addition, tumor cells from drug sensitive patients were more
      tumorigenic than those of drug resistance (p = 0.0013). Cisplatin treatment led
      to a sharp decrease of clonal formation of drug-sensitive cells but showed slight
      effects on drug resistant cells. Specific anti-miRs were then employed to
      downregulate the expression of microRNAs in primary tumor cells. Inhibition of
      miR-9 resulted in decreased clonal formation and sensitivity to cisplatin, while
      the knockdown of other three microRNAs did not show any influence in
      tumorigenesis and drug sensitivity. In conclusion, this study showed that in
      primary ovarian tumor cells, high expression of miR-9 was associated with
      enhanced tumorigenesis and increased sensitivity of the tumor cells to cisplatin
      treatment.

PMID- 25846739
TI  - Failure of self-disclosure of deferrable risk behaviors associated with
      transfusion-transmissible infections in blood donors.
AB  - BACKGROUND: To date, most studies on deferral of blood donors have focused on men
      who have sex with men (MSM) and/or injecting drug users. Few have examined
      deferrable risk behaviors relating to transfusion-transmissible infections (TTIs)
      in general. This study aimed to examine the prevalence of, and factors associated
      with, nondisclosure of TTI-related risk behaviors in donors. STUDY DESIGN AND
      METHODS: Chinese-speaking donors who had just given blood in Hong Kong were
      invited to self-complete an anonymous questionnaire. Practices of one or more of
      seven deferrable risk behaviors associated with TTI were inquired. Factors
      associated with noncompliance with self-disclosure were evaluated by logistic
      regression. RESULTS: Over a 4-week study period in 2012, a total of 1143 donors
      were recruited. Overall, 0.2% gave a history of drug injection, 1.7% had had sex
      with sex worker(s), and 0.3% had had sex with a human immunodeficiency virus
      infected partner, while none had been paid for sex. Some 1.5% of male donors
      reported having same-sex behaviors. Factors associated with noncompliance were
      male gender (odds ratio [OR] 31.1; 95% confidence interval [CI], 3.7-263.6),
      having multiple sex partners (OR, 89.7; 95% CI, 28.7-279.9), and previous history
      of temporary deferral (OR, 11.4; 95% CI, 2.5-53.3). If suspected noncompliance
      was included, the overall prevalence of nondisclosure of deferrable behaviors
      could be high at 6.5%. CONCLUSION: Albeit uncommon, some donors fail to provide
      accurate answers to predonation screening questions and are not deferred
      appropriately. There is room for improvement to make deferral policy acceptable
      and understandable, so as to minimize the risk of TTI. Efforts are also needed to
      tackle the paucity of data on noncompliance of non-MSM donors.

PMID- 25846740
TI  - Single-incision laparoscopic surgery through the umbilicus is associated with a
      higher incidence of trocar-site hernia than conventional laparoscopy: a meta
      analysis of randomized controlled trials.
AB  - BACKGROUND: Single-incision laparoscopic surgery has been developed with the
      objective to reduce surgical trauma, decrease associated surgical stress and to
      improve cosmetic outcome. However, concerns have been raised regarding the risk
      of trocar-site hernia following this approach. Previous meta-analyses have
      suggested a trend toward higher hernia rates, but have failed to demonstrate a
      significant difference between single-incision and conventional laparoscopic
      surgery. METHOD: Medline, AMED, CINAHL and CENTRAL were searched up to May 2014.
      Randomized controlled trials comparing single-incision and conventional
      laparoscopic surgery were considered for inclusion. Studies with patients aged
      less than 18 years and those reporting on robotic surgery were disregarded.
      Pooled odds ratios with 95% confidence intervals were calculated to measure the
      comparative risk of trocar-site hernia following single-incision and conventional
      laparoscopic surgery. RESULTS: Nineteen randomized trials encompassing 1705
      patients were included. Trocar-site hernia occurred in 2.2% of patients in the
      single-incision group and in 0.7% of patients in the conventional laparoscopic
      surgery group (odds ratio 2.26, 95% confidence interval 1.00-5.08, p = 0.05).
      Sensitivity analysis of quality randomized trials validated the outcome estimates
      of the primary analysis. There was no heterogeneity among studies (I2 = 0%) and
      no evidence of publication bias. CONCLUSION: Single-incision laparoscopic surgery
      involving entry into the peritoneal cavity through the umbilicus is associated
      with a slightly higher risk of trocar-site hernia than conventional laparoscopy.
      Its effect on long-term morbidity and quality of life is a matter for further
      investigation.

PMID- 25846741
TI  - Next steps for birth defects research and prevention: The birth defects study to
      evaluate pregnancy exposures (BD-STEPS).
AB  - BACKGROUND: The Birth Defects Study To Evaluate Pregnancy exposureS (BD-STEPS) is
      a population-based, multi-Center case-control study of modifiable risk factors
      for selected birth defects in the United States. BD-STEPS is the second major
      research effort of the Centers for Birth Defects Research and Prevention, which
      extends and expands the initial research effort, the National Birth Defects
      Prevention Study (NBDPS). METHODS: BD-STEPS focuses on 17 categories of
      structural birth defects selected based on severity, prevalence, consistent
      ascertainment, and previous findings that warrant additional research. Cases are
      identified through existing birth defects surveillance programs; controls are
      from vital records or birth hospital logs from the same catchment area. BD-STEPS
      uses a standardized computer-assisted telephone interview to collect information
      from case and control mothers on topics including demographics, health
      conditions, and medication use. Following the maternal interview, selected
      Centers request permission to sample residual newborn screening blood spots from
      state repositories for genetic analyses. New components planned for BD-STEPS
      include linkages with external datasets and use of online questionnaires to
      collect in-depth information on selected exposures. RESULTS: BD-STEPS extends
      NBDPS by continuing to collect data on many exposures that were assessed in
      NBDPS, allowing data from both studies to be combined and providing an
      unprecedented sample size to analyze rare exposures. BD-STEPS expands upon NBDPS
      by collecting more detailed information on existing exposures as well as new
      exposures. CONCLUSION: The goal of BD-STEPS is to provide women and healthcare
      providers with information they need to make decisions to promote the healthiest
      pregnancy possible.

PMID- 25846742
TI  - vapA (A-layer) typing differentiates Aeromonas salmonicida subspecies and
      identifies a number of previously undescribed subtypes.
AB  - Sequence variation in a region of the virulence array protein gene (vapA; A
      layer) was assessed in 333 ('typical' and 'atypical') isolates of the fish
      pathogenic bacterium Aeromonas salmonicida. Resulting similarity dendrograms
      revealed extensive heterogeneity, with nearly all isolates belonging to either of
      14 distinct clusters or A-layer types. All acknowledged A. salmonicida subspecies
      (except ssp. pectinolytica, from which no vapA sequence could be obtained) were
      clearly separated, and notably, all isolates phenotypically identified as ssp.
      salmonicida formed a distinct and exclusive A-layer type. Additionally, an array
      of un-subspeciated atypical strains formed several equally prominent clusters,
      demonstrating that the concept of typical/atypical A. salmonicida is
      inappropriate for describing the high degree of diversity evidently occurring
      outside ssp. salmonicida. Most representatives assessed in this study were
      clinical isolates of spatiotemporally diverse origins, and were derived from a
      variety of hosts. We observed that from several fish species or families,
      isolates predominantly belonged to certain A-layer types, possibly indicating a
      need for host-/A-layer type-specific A. salmonicida vaccines. All in all, A-layer
      typing shows promise as an inexpensive and rapid means of unambiguously
      distinguishing clinically relevant A. salmonicida subspecies, as well as
      presently un-subspeciated atypical strains. 

PMID- 25846743
TI  - Clinical implications of basic science discoveries: nociceptive neurons as
      targets to control immunity--potential relevance for transplantation.
AB  - Increasing evidence indicates the existence of a complex cross-regulation between
      the most important biosensors of the human body: The immune and nervous systems.
      Cytokines control body temperature and trigger autoimmune disorders in the
      central nervous system, whereas neuropeptides released in peripheral tissues and
      lymphoid organs modulate inflammatory (innate) and adaptive immune responses.
      Surprisingly, the effects of nerve fibers and the antidromic release of its pro
      inflammatory neuropeptides on the leukocytes of the immune system that mediate
      graft rejection are practically unknown. In the transplantation field, such area
      of research remains practically unexplored. A recent study by Riol-Blanco et al
      has revealed new details on how nociceptive nerves regulate the pro-inflammatory
      function of leukocytes in peripheral tissues. Although the mechanism(s) by which
      neuroinflammation affects the immune response against the allograft remains
      unknown, recent data suggest that this new area of research is worth exploring
      for potential development of novel complementary therapies for
      prevention/treatment of graft rejection. 

PMID- 25846744
TI  - Cytotoxic effects of chemokine receptor 4 inhibition by AMD3100 in biliary tract
      cancer cells: Potential drug synergism with gemcitabine.
AB  - Biliary tract cancer (BTC) remains one of the most life-threatening types of
      cancer due to the lack of efficient therapies. Advanced tumour stages at the
      point of diagnosis and high chemoresistance are two of the predominant reasons
      for a 5-year survival rate of only ~5%. The present study investigated the effect
      of the chemokine receptor 4 (CXCR4) inhibitor AMD3100 (Plerixafor), alone and in
      combination with standard gemcitabine chemotherapy, on the proliferation of BTC
      cells. The expression of CXCR4 was analysed by reverse transcription-quantitative
      polymerase chain reaction in eight heterogeneously differentiated BTC cell lines.
      The effects of treatment with the CXCR4 antagonist, AMD3100, on cell viability
      and anchorage-independent growth, and the possible synergistic cytotoxic effects
      of AMD3100 with standard chemotherapeutics were assessed. The expression of CXCR4
      was observed to a variable extent in all eight BTC cell lines, with SkChA-1 cells
      exhibiting the highest expression levels. Treatment with AMD3100 led to a
      marginal decrease in cell viability in the cell lines, with the exception of the
      CCSW-1 cells, and a significant reduction in the GBC, MzChA-1, SkChA.-1 and TFK-1
      cell lines. The combined treatment of the SkChA-1 cells with varying
      concentrations of AMD3100 and standard gemcitabine chemotherapy revealed a more
      marked overall cytotoxicity, indicating a potential synergistic effect. In
      addition, AMD3100 significantly reduced anchorage-independent growth in the SkChA
      1 cells. Overall, the results of the present study suggest that the inhibition of
      CXCR4 by AMD3100, in combination with gemcitabine, may be a suitable strategy for
      the future therapy of BTC.

PMID- 25846745
TI  - Systematic review of experimental studies on intestinal anastomosis.
AB  - BACKGROUND: The contribution of animal research to a reduction in clinical
      intestinal anastomotic leakage is unknown, despite numerous experimental studies.
      In view of the current societal call to replace, reduce and refine animal
      experiments, this study examined the quality of animal research related to
      anastomotic healing and leakage. METHODS: Animal studies on intestinal
      anastomotic healing were retrieved systematically from PubMed and Embase. Study
      objective, conclusion and animal model were recorded. Reporting quality and
      internal validity (reporting of randomization and blinding) were assessed.
      RESULTS: A total of 1342 studies were identified, with a rising publication rate.
      The objectives of most studies were therapeutic interventions (64.8 per cent) and
      identification of risk factors (27.5 per cent). Of 350 articles studying
      experimental therapies, 298 (85.1 per cent) reported a positive effect on
      anastomotic healing. On average, 44.7 per cent of relevant study characteristics
      were not reported, in particular details on anastomotic complications (31.6 per
      cent), use of antibiotics (75.7 per cent), sterile surgery (83.4 per cent) and
      postoperative analgesia (91.4 per cent). The proportion of studies with
      randomization, blinding of surgery and blinding of primary outcome assessment has
      increased in the past two decades but remains insufficient, being included in
      only 62.4, 4.9 and 8.5 per cent of publications respectively. Animal models
      varied widely in terms of species, method to compromise healing, intestinal
      segment and outcome measures used. CONCLUSION: Animal research on anastomotic
      leakage is of poor quality and still increasing, contrary to societal aims.
      Reporting and study quality must improve if results are to impact on patients.

PMID- 25846747
TI  - Hand therapy following elbow release for passive elbow flexion and long head of
      the triceps transfer for active elbow flexion in children with amyoplasia.
AB  - Children born with the Amyoplasia form of arthrogryposis multiplex congenita
      (AMC) who lack elbow flexor muscles and have elbow extension contractures usually
      require assistance in performing ADL's that require reaching their hand to their
      face, head, and upper body. For tasks involving the UE, the elbow is the key to
      functional independence. Children born with Amyoplasia may benefit from selective
      surgeries to enhance functional independence and improve quality of life. Home
      therapy and splinting following these surgeries is an important part of gaining
      motion and improving function. This abstract will review the rehab and splinting
      following an elbow release to gain passive elbow flexion, and a long head of the
      triceps transfer for active elbow flexion in children with Amyoplasia. 

PMID- 25846746
TI  - Adolescent girls' neural response to reward mediates the relation between
      childhood financial disadvantage and depression.
AB  - BACKGROUND: Children who experience socioeconomic disadvantage are at heightened
      risk for developing depression; however, little is known about neurobiological
      mechanisms underlying this association. Low socioeconomic status (SES) during
      childhood may confer risk for depression through its stress-related effects on
      the neural circuitry associated with processing monetary rewards. METHODS: In a
      prospective study, we examined the relationships among the number of years of
      household receipt of public assistance from age 5-16 years, neural activation
      during monetary reward anticipation and receipt at age 16, and depression
      symptoms at age 16 in 123 girls. RESULTS: Number of years of household receipt of
      public assistance was positively associated with heightened response in the
      medial prefrontal cortex during reward anticipation, and this heightened neural
      response mediated the relationship between socioeconomic disadvantage and current
      depression symptoms, controlling for past depression. CONCLUSIONS: Chronic
      exposure to socioeconomic disadvantage in childhood may alter neural circuitry
      involved in reward anticipation in adolescence, which in turn may confer risk for
      depression.

PMID- 25846748
TI  - The conservation profile of a protein bears the imprint of the molecule that is
      evolutionarily coupled to the protein.
AB  - The conservation profile of a protein is a curve of the conservation levels of
      amino acids along the sequence. Biologists are usually more interested in
      individual points on the curve (namely, the conserved amino acids) than the
      overall shape of the curve. Here, we show that the conservation curves of
      proteins bear the imprints of molecules that are evolutionarily coupled to the
      proteins. Our method is based on recent studies that a sequence conservation
      profile is quantitatively linked to its structural packing profile. We find that
      the conservation profiles of nucleic acid (NA) binding proteins are better
      correlated with the packing profiles of the protein-NA complexes than those of
      the proteins alone. This indicates that a nucleic acid binding protein evolves to
      accommodate the nucleic acid in such a way that the residues involved in binding
      have their conservation levels closely coupled with the specific nucleotides.

PMID- 25846749
TI  - TBBPA induces developmental toxicity, oxidative stress, and apoptosis in embryos
      and zebrafish larvae (Danio rerio).
AB  - Tetrabromobisphenol A (TBBPA) is currently one of the most frequently used
      brominated flame retardants and can be considered as a high production volume
      chemical. In this study, zebrafish embryos and larvae served as a biological
      model to evaluate TBBPA-induced developmental toxicity, oxidative stress, oxidant
      associated gene expression, and cell apoptosis. Abnormalities, including
      hyperemia and pericardial edema, were induced in zebrafish larvae. The results
      showed that toxicity endpoints such as hatching rate, survival rate, malformation
      rate, and growth rate had a significant dose-response relationship with TBBPA.
      Further studies revealed that TBBPA did not alter the enzyme activities of
      Copper/Zinc Superoxide dismutase (Cu/Zn-SOD), catalase (CAT), and
      glutathioneperoxidase (GPx) at 0.10 mg/L, but decreased activities following
      exposure to 0.40, 0.70, and 1.00 mg/L. Despite the significantly decreased gene
      expression of Cu/Zn-SOD, CAT, and GPx1a in the 1.00 mg/L treatment group, other
      treatments (0.10, 0.40, 0.70 mg/L) did not alter gene expression. Moreover,
      Acridine orange staining results showed that apoptotic cells mainly accumulated
      in the brain, heart, and tail, indicating possible TBBPA-induced brain, cardiac,
      and blood circulation system impairment in zebrafish embryos and larvae.
      Histological analysis also showed evidence of obvious heart impairment in TBBPA
      treated groups. This study provides new evidence on the developmental toxicity,
      oxidative stress, and apoptosis of embryos and zebrafish larvae, which is
      important for the evaluation of environmental toxicity and chemical risk. (c)
      2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1241-1249, 2016. 

PMID- 25846750
TI  - Role of PO4 tetrahedron in LiFePO4 and FePO4 system.
AB  - Using high resolution transmission electron microscopy with image simulation and
      Fourier analysis, the Li1- x FePO4 (x < 0.01), Li1- x FePO4 (x ~ 0.5), and FePO4
      particles, prepared by charging or discharging the 053048 electrochemical cells
      (thickness: 5 mm, width: 30 mm, height: 48 mm) and dismantled inside an Ar-filled
      dry box, were investigated. The high resolution images reveal: (1) the solid
      solution of Li1- x FePO4 (x < 0.01) contains some missing Li ions leading PO4
      group distorted around M1 tunnel of the unit cell; (2) the texture of the
      particles of Li1- x FePO4 (x ~0.5) has homogeneously distributed compositional
      domains of LiFePO4 and FePO4 resulting from spinodal decomposition which promote
      Li ion easily getting into the particle due to uphill diffusion, (3) the
      particles of FePO4 formed in charging have heavily distorted lattice and contain
      some isolated LiFePO4 , (4) interface between LiFePO4 and FePO4 and between
      amorphous and crystal region provides the lattice distortion of small polarons.

PMID- 25846751
TI  - Re: Steven Joniau, Alberto Briganti, Paolo Gontero, et al. Stratification of High
      risk Prostate Cancer into Prognostic Categories: A European Multi-institutional
      Study. Eur Urol 2015;67:157-64.

PMID- 25846752
TI  - Aspirin counteracts cancer stem cell features, desmoplasia and gemcitabine
      resistance in pancreatic cancer.
AB  - Pancreatic ductal adenocarcinoma (PDA) is characterized by an extremely poor
      prognosis. An inflammatory microenvironment triggers the pronounced desmoplasia,
      the selection of cancer stem-like cells (CSCs) and therapy resistance. The anti
      inflammatory drug aspirin is suggested to lower the risk for PDA and to improve
      the treatment, although available results are conflicting and the effect of
      aspirin to CSC characteristics and desmoplasia in PDA has not yet been
      investigated. We characterized the influence of aspirin on CSC features, stromal
      reactions and gemcitabine resistance. Four established and 3 primary PDA cell
      lines, non-malignant cells, 3 patient tumor-derived CSC-enriched spheroidal
      cultures and tissues from patients who did or did not receive aspirin before
      surgery were analyzed using MTT assays, flow cytometry, colony and spheroid
      formation assays, Western blot analysis, antibody protein arrays, electrophoretic
      mobility shift assays (EMSAs), immunohistochemistry and in vivo
      xenotransplantation. Aspirin significantly induced apoptosis and reduced the
      viability, self-renewal potential, and expression of proteins involved in
      inflammation and stem cell signaling. Aspirin also reduced the growth and
      invasion of tumors in vivo, and it significantly prolonged the survival of mice
      with orthotopic pancreatic xenografts in combination with gemcitabine. This was
      associated with a decreased expression of markers for progression, inflammation
      and desmoplasia. These findings were confirmed in tissue samples obtained from
      patients who had or had not taken aspirin before surgery. Importantly, aspirin
      sensitized cells that were resistant to gemcitabine and thereby enhanced the
      therapeutic efficacy. Aspirin showed no obvious toxic effects on normal cells,
      chick embryos or mice. These results highlight aspirin as an effective,
      inexpensive and well-tolerated co-treatment to target inflammation, desmoplasia
      and CSC features PDA. 

PMID- 25846754
TI  - Genomics of adaptation to host-plants in herbivorous insects.
AB  - Herbivorous insects represent the most species-rich lineages of metazoans. The
      high rate of diversification in herbivorous insects is thought to result from
      their specialization to distinct host-plants, which creates conditions favorable
      for the build-up of reproductive isolation and speciation. These conditions rely
      on constraints against the optimal use of a wide range of plant species, as each
      must constitute a viable food resource, oviposition site and mating site for an
      insect. Utilization of plants involves many essential traits of herbivorous
      insects, as they locate and select their hosts, overcome their defenses and
      acquire nutrients while avoiding intoxication. Although advances in understanding
      insect-plant molecular interactions have been limited by the complexity of insect
      traits involved in host use and the lack of genomic resources and functional
      tools, recent studies at the molecular level, combined with large-scale genomics
      studies at population and species levels, are revealing the genetic underpinning
      of plant specialization and adaptive divergence in non-model insect herbivores.
      Here, we review the recent advances in the genomics of plant adaptation in
      hemipterans and lepidopterans, two major insect orders, each of which includes a
      large number of crop pests. We focus on how genomics and post-genomics have
      improved our understanding of the mechanisms involved in insect-plant
      interactions by reviewing recent molecular discoveries in sensing, feeding,
      digesting and detoxifying strategies. We also present the outcomes of large-scale
      genomics approaches aimed at identifying loci potentially involved in plant
      adaptation in these insects. 

PMID- 25846753
TI  - Targeting Toll-like receptor 2 inhibits growth of head and neck squamous cell
      carcinoma.
AB  - Infection-driven inflammation has been proposed to be involved in the
      tumorigenesis of head and neck squamous cell carcinoma (HNSCC). Oral HNSCC is
      often colonized with microbes such as gram-positive bacteria and yeast, where
      ligands derived from their wall components have been shown to specifically bind
      to Toll-like receptor 2 (TLR2). Although TLR2 has been described to be expressed
      in oral HNSCC, its function has not been well characterized. Here, we show the
      expression of TLR2 in both HNSCC cell lines and primary patient-derived HNSCC
      xenograft tumors. Activation of TLR2 with a yeast-derived ligand of TLR2,
      zymosan, promoted organoid formation in an ex vivo model of tumor growth, while
      blockade with anti-TLR2 antibodies inhibited organoid formation. Zymosan also
      induced phosphorylation of ERK and the p65 subunit of NF-kappaB, which was
      inhibited in the presence of anti-TLR2 antibodies, indicating that this receptor
      is functional in HNSCC and that the signaling through these pathways is intact.
      TLR2 blockade also inhibited growth of human xenografted tumors in
      immunodeficient mice. In summary, our data show that TLR2 is a functional
      receptor expressed in human HNSCC that plays a direct pro-tumorigenic role, and
      that it can be therapeutically targeted with blocking antibodies to reduce tumor
      growth. 

PMID- 25846756
TI  - Patterns of Dating Violence Perpetration and Victimization in U.S. Young Adult
      Males and Females.
AB  - Dating violence (DV) is frequently reported by young adults in intimate
      relationships in the United States, but little is known about patterns of DV
      perpetration and victimization. In this study, we examined sexual and physical
      violence perpetration and victimization reported by young adults to determine how
      the violence patterns differ by sex and race/ethnicity. Data from non-Hispanic
      White, non-Hispanic Black, and Hispanic participants in Wave 3 of the National
      Longitudinal Study of Adolescent to Adult Health were analyzed. DV was assessed
      using responses to four questions focused on perpetration and four questions
      focused on victimization. The information on DV was taken from the most violent
      relationship reported by participants prior to Wave 3. Latent class analysis was
      first conducted separately by sex, adjusting for age, race/ethnicity, and
      financial stress, then by race/ethnicity, adjusting for age and financial stress.
      Relative model fit was established by comparing Bayesian Information Criteria
      (BIC), adjusted BIC, entropy, interpretability of latent classes, and certainty
      of latent class assignment for covariate-adjusted models. The results indicate
      that patterns of violence differed by sex and for females, by race/ethnicity. A
      three-class model was the best fit for males. For females, separate four-class
      models were parsimonious for White, Black, and Hispanic females. Financial stress
      was a significant predictor of violence classification for males and females and
      age predicted membership in White and Black female models. Variations in DV
      patterns by sex and race/ethnicity suggest the need for a more nuanced
      understanding of differences in DV.

PMID- 25846757
TI  - Examining Intimate Partner Violence and Health Factors Among Rural Appalachian
      Pregnant Women.
AB  - Among pregnant women, intimate partner violence (IPV) is recognized as a critical
      risk factor in adverse health outcomes for the mother and newborn alike. This
      pilot study examined IPV and health for rural Appalachian pregnant women, a
      particularly vulnerable high-risk and high-needs group. Participants were 77
      rural, Appalachian pregnant women entering a hospital-based inpatient
      detoxification unit primarily for Opiate Dependence. Study participants gave
      informed consent to a face-to-face interview and secondary data abstraction from
      hospital medical records. IPV was measured via questions from the National
      Violence Against Women Survey, the Revised Conflict Tactics Scale (CTS2), and the
      Psychological Maltreatment of Women Inventory (PMWI). The majority of the sample
      reported lifetime psychological (89.6%) and physical (64.9%) violence. A little
      over three fourths (75.3%) experienced IPV in the past year. Furthermore, over
      one third (39.0%) experienced stalking, physical, or sexual violence in the past
      year. Most participants (71.4%) experienced psychological abuse in the past year.
      IPV experiences, in conjunction with pervasive substance use, mental and physical
      health problems, and poverty present in rural Appalachia, culminate in a
      particularly high-risk and high-needs group of pregnant women. These women
      present unique opportunities and challenges for prevention, intervention, and
      treatment.

PMID- 25846755
TI  - Nuclear processes associated with plant immunity and pathogen susceptibility.
AB  - Plants are sessile organisms that have evolved exquisite and sophisticated
      mechanisms to adapt to their biotic and abiotic environment. Plants deploy
      receptors and vast signalling networks to detect, transmit and respond to a given
      biotic threat by inducing properly dosed defence responses. Genetic analyses and,
      more recently, next-generation -omics approaches have allowed unprecedented
      insights into the mechanisms that drive immunity. Similarly, functional genomics
      and the emergence of pathogen genomes have allowed reciprocal studies on the
      mechanisms governing pathogen virulence and host susceptibility, collectively
      allowing more comprehensive views on the processes that govern disease and
      resistance. Among others, the identification of secreted pathogen molecules
      (effectors) that modify immunity-associated processes has changed the plant
      microbe interactions conceptual landscape. Effectors are now considered both
      important factors facilitating disease and novel probes, suited to study immunity
      in plants. In this review, we will describe the various mechanisms and processes
      that take place in the nucleus and help regulate immune responses in plants.
      Based on the premise that any process required for immunity could be targeted by
      pathogen effectors, we highlight and describe a number of functional assays that
      should help determine effector functions and their impact on immune-related
      processes. The identification of new effector functions that modify nuclear
      processes will help dissect nuclear signalling further and assist us in our bid
      to bolster immunity in crop plants. 

PMID- 25846758
TI  - Understanding Disparities in Service Seeking Following Forcible Versus Drug- or
      Alcohol-Facilitated/Incapacitated Rape.
AB  - Victims of drug- or alcohol-facilitated/incapacitated rape (DAFR/IR) are
      substantially less likely to seek medical, rape crisis, or police services
      compared with victims of forcible rape (FR); however, reasons for these
      disparities are poorly understood. The current study examined explanatory
      mechanisms in the pathway from rape type (FR vs. DAFR/IR) to disparities in post
      rape service seeking (medical, rape crisis, criminal justice). Participants were
      445 adult women from a nationally representative household probability sample who
      had experienced FR, DAFR/IR, or both since age 14. Personal characteristics (age,
      race, income, prior rape history), rape characteristics (fear, injury, loss of
      consciousness), and post-rape acknowledgment, medical concerns, and service
      seeking were collected. An indirect effects model using bootstrapped standard
      errors was estimated to examine pathways from rape type to service seeking.
      DAFR/IR-only victims were less likely to seek services compared with FR victims
      despite similar post-rape medical concerns. FR victims were more likely to report
      fear during the rape and a prior rape history, and to acknowledge the incident as
      rape; each of these characteristics was positively associated with service
      seeking. However, only prior rape history and acknowledgment served as indirect
      paths to service seeking; acknowledgment was the strongest predictor of service
      seeking. Diminished acknowledgment of the incident as rape may be especially
      important to explaining why DAFR/IR victims are less likely than FR victims to
      seek services. Public service campaigns designed to increase awareness of rape
      definitions, particularly around DAFR/IR, are important to reducing disparities
      in rape-related service seeking.

PMID- 25846759
TI  - Age, Marital Status, and Risk of Sexual Victimization: Similarities and
      Differences Across Victim-Offender Relationships.
AB  - By now, age and marital status are well-established correlates of criminal
      victimization, including adult women's sexual victimization. National crime
      statistics, as well as a large body of scholarly literature, have specified that
      younger women and unmarried women are at comparatively higher risk of sexual
      victimization than older women and married women. Few studies, however, have
      examined the relationship between age, marital status, and risk of victimization
      across diverse situational contexts of sexual victimization. The current study
      used data from the National Crime Victimization Survey (NCVS) to examine whether
      the relationship between age, marital status, and risk of sexual victimization
      varied across victimization experiences involving three victim-offender
      relationships: stranger, acquaintance, and intimate partner. Results indicate
      both similarities and differences in the relationship between age, marital
      status, and risk of victimization across these three situational contexts of
      victimization. As expected, age was a significant predictor of victimization in
      all models; however, younger women's increased risk of victimization was far more
      pronounced for acquaintance and intimate partner victimization experiences as
      compared with stranger experiences. Also, consistent with prior research,
      unmarried women were at higher risk of victimization in all models; however,
      within unmarried status categories, separated women were at highest risk of both
      intimate partner and acquaintance victimization experiences as compared with
      never married or divorced women.

PMID- 25846760
TI  - The Use of Anthracyclines for Therapy of CNS Tumors.
AB  - Despite being long lived, anthracyclines remain the "evergreen" drugs in clinical
      practice of oncology, showing a potent effect in inhibiting cell growth in many
      types of tumors, including brain neoplasms. Unfortunately, they suffer from a
      poor penetration into the brain when intravenously administered due to multidrug
      resistance mechanism, which hampers their delivery across the blood brain
      barrier. In this paper, we summarize the current literature on the role of
      anthracyclines in cancer therapy and highlight recent efforts on 1) development
      of tumor cell resistance to anthracyclines and 2) the new approaches to brain
      drug delivery across the blood brain barrier. 

PMID- 25846761
TI  - A Novel Approach to Inhibit Heat Shock Response as Anticancer Strategy by
      Coumarine Compounds Containing Thiazole Skeleton.
AB  - Inhibition of the Hsp90 function is an essential therapeutic approach and several
      inhibitors were designed as anti-cancer agents. These inhibitors are ATPases and
      they aim to deregulate Hsp90 folding function. ATPase proteins are common in
      human metabolism but they form nonspecific targets. Hsp90 functions as dimer with
      coordinating chaperones. Heat Shock Organizing Protein (Hop) forms a bridge
      between Hsp90 and Hsp70-Hsp40 complex to form Hsp90-Hsp70 coordination.
      Perturbing conformational changes of these Hsp proteins, dimer formation, and
      protein-protein interactions inhibit Hsp90 substrate protein folding function.
      This approach does not target all ATPase proteins but targets Hsp90 function
      solely. For this purpose, we designed compounds to block Hsp90 function.
      Moreover, molecular docking studies as well as competition analysis of the
      compounds were performed with Hsp90. Novel thiazolyl coumarine compounds were
      determined as valuable C-terminal Hsp90 inhibitors and provide promising
      templates for the drug design. Anticancer activities of these novel compounds
      were tested by employing human colon (DLD-1) and liver cancer (HepG2) cell lines.
      Thiazolyl coumarine compounds are found to be significant and useful for the
      treatment of human colon and liver cancer as evidenced by in vitro and in silico
      results. 

PMID- 25846762
TI  - Dichloroacetate stimulates changes in the mitochondrial network morphology via
      partial mitophagy in human SH-SY5Y neuroblastoma cells.
AB  - Dichloroacetate (DCA) is beneficial in cancer therapy because it induces
      apoptosis and decreases cancer growth in vitro and in vivo without affecting non
      cancer cells. DCA stimulates the activity of the enzyme pyruvate dehydrogenase by
      inhibiting pyruvate dehydrogenase kinase. Consequently, DCA promotes oxidative
      phosphorylation after glycolysis. Therefore, DCA produces changes in energy
      metabolism that could affect the mitochondrial network and mitophagy. This
      investigation determined the effects of DCA treatment on mitophagy in human
      neuroblastoma SH-SY5Y cells. SH-SY5Y cells were cultured and distributed into 3
      groups: control, NH4Cl and chloroquine. Each group was treated with DCA at 0, 5,
      30 and 60 mM for 16 h. Samples were analyzed for cell viability, mtDNA copy
      number, mitochondrial network morphology and expression of key proteins involved
      in mitochondrial dynamics, such as LC3b, FIS1, OPA1, PARKIN and PINK1. In all
      groups, DCA caused a decrease in cell viability, an induction of autophagy in a
      dose-dependent manner and a decrease in Tim23, FIS1 and PARKIN protein
      expression, leading to profound morphological changes in the mitochondrial
      network resulting in shorter and more fragmented filaments. However, TFAM protein
      levels remained unchanged. Similarly, the mitochondrial copy number was not
      significantly different among the treatment groups. In conclusion, DCA induces
      mitophagy and remodeling of the mitochondrial network. In this remodeling, DCA
      induces a decrease in the expression of key proteins involved in protein
      degradation and mitochondrial dynamics but does not significantly affect the
      mtDNA density. Blocking late phase autophagy increases the effects of DCA,
      suggesting that autophagy protects the cell, at least partially, against DCA.

PMID- 25846763
TI  - Configurable Nanosized Metal Oxide Oligomers via Precise "Click" Coupling Control
      of Hybrid Polyoxometalates.
AB  - Polyoxometalates (POMs) are discrete clusters of redox-active metal oxides, many
      of which can be linked to organic moieties. Here, we show how it is possible to
      link Mn Anderson POMs to terminal alkyne and azide groups and develop appropriate
      conditions for their Cu-catalyzed alkyne-azide cycloaddition (or "click"
      reaction). These coupling reactions are then used to link the clusters together,
      forming monodisperse linear Mn Anderson oligomers, here with examples ranging in
      size from two to five clusters. These oligomers are built up sequentially using a
      combination of mono- and difunctionalized clusters, giving an unprecedented level
      of control over the size and structure of the resulting hybrid POMs. This new
      synthetic methodology therefore opens the way for the synthesis of metal oxide
      hybrid oligomers and polymers by coupling control, minimizing side products,
      producing nanosized molecular hybrid organic-inorganic oxides ca. 4-9 nm in size,
      with molecular weights ranging 2-10 kDa. 

PMID- 25846764
TI  - Frequency of renal artery stenosis after renal denervation in patients with
      resistant arterial hypertension.
AB  - Catheter-based ablation of nerves in the adventitia of renal arteries (renal
      artery denervation [RAD]) using radiofrequency energy can reduce blood pressure
      (BP) in patients with resistant arterial hypertension (RAH). Occurrence of renal
      artery stenosis after RAD is still an important concern. We systematically
      investigated the renal artery anatomy using magnetic resonance imaging (MRI) or
      computed tomography (CT) angiography in a consecutive series of patients 6 months
      after RAD. Patients with RAH were treated by RAD after exclusion of secondary
      causes of hypertension. RAH was defined by a mean systolic office BP >160 mm Hg.
      Renal artery imaging was performed 6 months after RAD by MRI angiography. In case
      of any contraindication for MRI, a CT angiography was performed. The primary end
      point was the incidence of significant renal artery stenosis (>=70% lumen
      diameter reduction). RAD was performed in 76 patients, and evaluation of renal
      artery anatomy by MRI (n = 66; 87%) or CT angiography (n = 10; 13%) was performed
      in all patients 6 months after RAD. We found no renal artery stenosis but 2 cases
      of new nonsignificant stenosis (50% TO 69% lumen diameter reduction). In
      responders, mean systolic office BP reduction was -30 mm Hg (p <0.001) and mean
      systolic 24-hour BP reduction was -18 mm Hg (p <0.001). In conclusion, the
      incidence of significant renal artery stenosis 6 months after RAD seems to be
      very low. However, late-onset development of nonsignificant renal artery
      narrowing cannot be excluded in some patients and should be anticipated in the
      case of RAH relapse or worsening of renal function after successful RAD. 

PMID- 25846765
TI  - Comparison of aortic annulus size by transesophageal echocardiography and
      computed tomography angiography with direct surgical measurement.
AB  - This study sought to compare the accuracy of 2-dimensional transesophageal
      echocardiography (TEE) and computed tomography angiography (CTA) for noninvasive
      aortic annular sizing as required for transcatheter aortic valve implantation
      (TAVI). Direct intraoperative (OR) sizing is the gold standard for aortic annular
      measurement in surgical aortic valve replacement. Unlike surgical aortic valve
      replacement, TAVI requires noninvasive assessment of aortic annular dimensions
      for determining the size of prosthesis to be implanted and controversy exists
      regarding the best imaging technique for TAVI sizing. Preoperative CTA and OR TEE
      images of the aortic annulus in 227 patients who underwent proximal aortic
      surgery with OR annular sizing at the Duke University Medical Center were
      reviewed. Both imaging techniques were compared with direct OR measurements of
      aortic annulus diameter using metric sizers as the gold standard. CTA
      overestimated aortic annulus diameter in 72.2% of cases, with 46.3% >1 TAVI valve
      size (>3 mm) overestimations, whereas TEE underestimated aortic annulus diameter
      in 51.1% of cases, with 16.7% >1 valve-size underestimations. Combining both
      techniques improved the estimation of aortic annular size. In conclusion, there
      are limitations to current imaging techniques for noninvasive determination of
      aortic annular dimensions compared with direct OR sizing. Undersizing by TEE and
      oversizing by CTA are common and may be related to differences in methods for
      sizing an elliptical structure. Combining measurements from both techniques would
      decrease the false exclusion rate for TAVI eligibility because of size mismatch. 

PMID- 25846766
TI  - Effects of the Mueller maneuver on functional mitral regurgitation and
      implications for obstructive sleep apnea.
AB  - Obstructive sleep apnea is prevalent and adversely affects cardiovascular health.
      However, little is known of the acute effects of an obstructive apnea on
      cardiovascular physiology. We hypothesized that pre-existing functional mitral
      regurgitation (MR) would worsen during performance of a Mueller maneuver (MM)
      used to simulate an obstructive apnea; 15 subjects with an ejection fraction
      <=35% and pre-existing functional MR were studied with Doppler echocardiography.
      The radius of the proximal flow convergence was used as a measure of mitral
      regurgitant flow. Measurements were made at baseline, during the MM, and post-MM.
      Areas of all 4 chambers were also measured at these time points, both in systole
      and diastole. Mean flow convergence radius for the group decreased significantly
      during the transition from the late-MM to post-MM (0.65 -> 0.57 mm, p = 0.001),
      implying increased MR during the MM. In addition, in 3 subjects, duration of MR
      increased during the MM. Right atrial (RA) areas, both systolic and diastolic,
      increased during the maneuver, whereas RA fractional area change decreased,
      indicating reduced RA emptying. Left ventricular emptying decreased early in the
      maneuver, probably because of the increased afterload burden, and then recovered.
      In conclusion, high negative intrathoracic pressure produces changes that,
      repeated hundreds of times per night in patients with obstructive sleep apnea,
      have the potential to worsen heart failure and predispose affected subjects to
      atrial fibrillation. 

PMID- 25846767
TI  - Contemporary Use of Ticagrelor in Interventional Practice (from Blue Cross Blue
      Shield of Michigan Cardiovascular Consortium).
AB  - Ticagrelor has greater antiplatelet activity than clopidogrel and is approved for
      use in patients with acute coronary syndrome (ACS). There are limited data on use
      of ticagrelor in real-world practice. We assessed ticagrelor use in 64,600
      patients who underwent percutaneous coronary intervention from January 2012 to
      March 2014 at 47 Michigan hospitals in the Blue Cross Blue Shield of Michigan
      Cardiovascular Consortium. Preprocedural risk of major adverse events was
      estimated with Blue Cross Blue Shield of Michigan Cardiovascular Consortium risk
      prediction models. The proportion of patients receiving clopidogrel, prasugrel,
      and ticagrelor was 72% (n = 46,864), 20% (n = 12,596), and 8% (n = 5,140),
      respectively, using ticagrelor increasing over time. Ticagrelor was used at 45
      hospitals, ranging from 0.5% to 64.9% of discharges. Patients receiving
      ticagrelor were older (63.6 vs 59.4), more often women (32.9% vs 26.7%), and were
      more likely to present with ST-segment elevation myocardial infarction (24.4% vs
      18.8%), cardiogenic shock within 24 hours (1.3% vs 0.9%), and anginal class IV
      (47.8% vs 43.0%) (p <0.05). Compared with prasugrel, ticagrelor was prescribed in
      patients with a higher predicted risk of percutaneous coronary intervention
      complications: contrast nephropathy (2.5% vs 1.6%), transfusion (2.2% vs 1.4%),
      and death (1.2% vs 0.7%) (p <0.001); >10% of patients were given prasugrel or
      ticagrelor for a non-ACS indication. Ticagrelor is prescribed to a higher risk
      population, and 1 in 10 patients prescribed ticagrelor or prasugrel did not have
      ACS. 

PMID- 25846768
TI  - Relation of polymorphism of the histidine decarboxylase gene to chronic heart
      failure in Han Chinese.
AB  - Histidine decarboxylase (HDC) is a key determinant of the levels of endogenous
      histamine that has long been recognized to play important pathophysiological
      roles during development of chronic heart failure (CHF). Meanwhile, certain
      genetic variants in HDC gene were reported to affect the function of HDC and
      associated with histamine-related diseases. However, the relation between
      polymorphisms of HDC gene and CHF risk remains unclear. This study aims to
      investigate the associations between 2 nonsynonymous HDC polymorphisms
      (rs17740607 and rs2073440) and CHF. We designed a 2-stage case-control study, in
      which we genotyped 439 patients with CHF and 467 healthy controls recruited in
      Xi'an, China, and replicated this study in 413 patients with CHF and 452 healthy
      subjects in Kunming, China. We also performed in vitro experiments to further
      validate the functional consequences of variants positively associated with CHF.
      The rs17740607 polymorphism showed replicated associations with all-cause CHF
      according to genotype and allele distribution and also under a dominant and
      additive genetic model after adjusted for traditional cardiovascular-related
      factors. Functional experiments further demonstrated that rs17740607 polymorphism
      decreased the HDC activity. In conclusion, HDC rs17740607 polymorphism is at
      least a partial loss-of-function variant and acts as a protective factor against
      CHF, which provides novel highlights for investigating the contribution of CHF. 

PMID- 25846769
TI  - H19 lncRNA mediates 17beta-estradiol-induced cell proliferation in MCF-7 breast
      cancer cells.
AB  - Estrogen plays a critical role in breast cancer development and progression.
      However, the mechanism involved in the promotion of breast cancer development and
      progression by estrogen remains unclear although it has been intensively studied.
      In the present study, we investigated the estrogen inducibility and functional
      significance of H19 lncRNA in breast cancer cells and tumor tissues. The
      screening of 83 disease-related long non-coding RNAs (lncRNAs) revealed that H19
      lncRNA was much higher in estrogen receptor (ER)-positive MCF-7 breast cancer
      cells than in ER-negative MDA-MB-231 cells. 17beta-estradiol produced a dose- and
      time-dependent induction of H19 expression in MCF-7 cells, which was mediated via
      ERalpha as evident by the blockade of this 17beta-estradiol effect with ICI
      182780, a specific ER antagonist and knockdown of ERalpha using specific RNAi.
      Moreover, knockdown of H19 lncRNA decreased cell survival and blocked estrogen
      induced cell growth while overexpression of H19 lncRNA stimulated cell
      proliferation. Quantitation of H19 lncRNA in human breast cancer tissues showed
      that the level of H19 lncRNA was >10-fold higher in ER-positive than in ER
      negative tumor tissues. These results suggest that H19 is an estrogen-inducible
      gene and plays a key role in cell survival and in estrogen-induced cell
      proliferation in MCF-7 cells, indicating that H19 lncRNA may serve as a biomarker
      for breast cancer diagnosis and progression, and as a valuable target for breast
      cancer therapy.

PMID- 25846770
TI  - A case of colonic solitary polypoid ganglioneuroma with a feature of inverted
      hyperplastic polyp.

PMID- 25846771
TI  - Boy Crisis? Sex Differences in Self-Injurious Behaviors and the Effects of Gender
      Role Conflicts Among College Students in China.
AB  - In Western research, self-injurious behaviors are commonly viewed as "feminine"
      behavior. In this present study, using the data from a survey administered to 960
      first- and second-year students in Xi'an Jiaotong University in China, the self
      injurious behaviors among college students are analyzed by sex. The results
      reported that the average prevalence of self-injurious behaviors among male
      students is 35.2%, higher than the 20.4% observed among female students (p < .1),
      and the average frequency of severe self-injurious behaviors among male students
      is 0.4, higher than the 0.18 reported among female students (p < .05). Gender
      role conflicts and verbal violence are strongly associated with male students'
      self-injurious behaviors, whereas gender role conflicts and verbal, visual, and
      sexual violence are strongly associated with female students' self-injurious
      behaviors. This suggests that self-injurious behaviors among college students in
      China constitute, to some extent, a boy crisis that can be well explained by
      gender role conflicts. In addition, verbal violence leads to self-injurious
      behaviors among both male and female students, whereas visual and sexual violence
      lead to self-injurious behaviors only among female students.

PMID- 25846779
TI  - Elevated GFAP Protein in Anterior Cingulate Cortical White Matter in Males With
      Autism Spectrum Disorder.
AB  - Based on evidence of abnormalities in axon thickness and neuronal
      disorganization, autism spectrum disorder (ASD) is commonly considered to be a
      condition resulting from neuronal dysfunction. Yet, recent findings suggest that
      non-neuronal cell types also contribute to ASD pathology. To investigate the role
      of glial cells in ASD, a combination of protein and gene expression analyses were
      used to determine levels of two glial markers, glial fibrillary acidic protein
      (GFAP) and myelin oligodendrocyte glycoprotein (MOG), in the postmortem brain
      tissue from control and ASD donors. Levels of GFAP immunoreactivity (ir) were
      significantly elevated (P = 0.008) in anterior cingulate cortex (Brodmann area
      24; BA24) white matter of ASD donors compared to control donors. In contrast,
      GFAP-ir levels were similar in BA24 gray matter from ASD and control donors. MOG
      ir was also similar in both BA24 white and gray matter from ASD and control
      donors. In anterior prefrontal cortex (BA10), there were no significant
      differences in GFAP-ir or MOG-ir in either white or gray matter comparing ASD to
      control donors. Levels of expression of the genes GFAP and MOG also showed no
      differences between control and ASD donors in BA24 and BA10 white and gray
      matter. Collectively, these data imply that ASD is associated with an activation
      of white matter astrocytes in the anterior cingulate cortex as a result of a yet
      undefined cellular insult. Research is needed to investigate the molecular
      pathways that underlie this astrocyte reaction and such research may yield
      important clues regarding the etiology of ASD.

PMID- 25846772
TI  - Adaptation of a Couple-Based HIV/STI Prevention Intervention for Latino Men Who
      Have Sex With Men in New York City.
AB  - Predominantly Spanish-speaking Latino men who have sex with men (MSM) and their
      same-sex partners continue to be at high risk for HIV and STIs. Behavioral
      research has identified how relationship dynamics for male couples are associated
      with sexual risk behavior. Connect 'n Unite (CNU), an evidence-based HIV/STI
      prevention intervention originally created for Black MSM and their same-sex
      partners, was adapted for predominantly Spanish-speaking Latino MSM and their
      same-sex partners on the assumption that its key elements would be translatable
      while its efficacy would be retained. A systematic adaptation process utilizing
      qualitative methods was used, including intervention adaptation sessions with 20
      predominantly Spanish-speaking Latino gay couples and 10 health service
      providers. The process included five steps: (1) engaging community stakeholders,
      (2) capturing the lived experiences of Latino gay couples, (3) identifying
      intervention priorities, (4) integrating the original intervention's social
      cognitive theory into a relationship-oriented, ecological framework for Latino
      gay couples, and (5) adapting intervention activities and materials. The adapted
      intervention, which we called Latinos en Pareja or Latinos in a Relationship,
      incorporates elements that effective HIV prevention interventions share,
      including: a solid theoretical foundation; emphasis on increasing risk reduction
      norms, sexual communication skills and social support for protection; and
      guidance on how to utilize available, culturally and linguistically appropriate
      services. The systematic adaptation approach used for a couples-based HIV
      prevention intervention also can be employed by other researchers and community
      stakeholders to adapt evidence-based interventions that promote wellness, linkage
      to care, and disease prevention for populations not originally targeted.

PMID- 25846780
TI  - The use and abuse of questionnaires in veterinary medicine.

PMID- 25846794
TI  - Response to: Fuller et al., "Glenosphere disengagement in a reverse total
      shoulder arthroplasty with a non-Morse taper design".

PMID- 25846795
TI  - The prevalence of developmental dysplasia of the hip in idiopathic clubfoot: a
      systematic review and meta-analysis.
AB  - PURPOSE: Developmental dysplasia of the hip (DDH) and idiopathic clubfoot are
      both common paediatric orthopaedic conditions. There is conflicting evidence in
      the literature as to whether the prevalence of DDH is higher in children with
      idiopathic clubfoot. The aim of our study was to systematically review the
      literature and determine the prevalence of DDH in idiopathic clubfoot. METHODS:
      We searched several databases from 1946 to 2014 for observational studies that
      reported the prevalence of DDH in idiopathic clubfoot. We performed a meta
      analysis using random effects model to pool the prevalence of DDH in idiopathic
      clubfoot. We also investigated the imaging modality utilised to diagnose and
      treat DDH in idiopathic clubfoot. Descriptive, quantitative and qualitative data
      were extracted. RESULTS: Twelve studies (ten case series, one retrospective
      cohort and one retrospective case-control) were eligible for the meta-analysis,
      with a total of 2,549 children with idiopathic clubfoot including 83 with DDH.
      The pooled prevalence estimate of DDH in children with idiopathic clubfoot was
      4.1% (95% CI, 2.1-7.7%). There was a substantial amount of between study
      heterogeneity (I (2)  = 87.1%, p < 0.001) due to variability between studies
      rather than chance variability. Sensitivity analyses showed that the pooled
      prevalence estimate was 3.5% (95% CI, 1.1-10.8 %) and 3.8% (95% CI, 1.0-13.7%)
      for studies utilising ultrasound as the imaging modality of diagnosis and
      treatment with a Pavlik harness respectively. CONCLUSIONS: The overall pooled
      prevalence of DDH in idiopathic clubfoot is similar to the normal population. The
      cumulative evidence at present does not indicate an association between DDH and
      idiopathic clubfoot. Therefore, we do not recommend routine screening for DDH in
      children with idiopathic clubfoot. However, future retrospective and/or
      prospective cohort studies of better quality will be able to answer this question
      with more certainty.

PMID- 25846796
TI  - Oxygen-sensing PHDs regulate bone homeostasis through the modulation of
      osteoprotegerin.
AB  - The bone microenvironment is composed of niches that house cells across variable
      oxygen tensions. However, the contribution of oxygen gradients in regulating bone
      and blood homeostasis remains unknown. Here, we generated mice with either single
      or combined genetic inactivation of the critical oxygen-sensing prolyl
      hydroxylase (PHD) enzymes (PHD1-3) in osteoprogenitors. Hypoxia-inducible factor
      (HIF) activation associated with Phd2 and Phd3 inactivation drove bone
      accumulation by modulating osteoblastic/osteoclastic cross-talk through the
      direct regulation of osteoprotegerin (OPG). In contrast, combined inactivation of
      Phd1, Phd2, and Phd3 resulted in extreme HIF signaling, leading to polycythemia
      and excessive bone accumulation by overstimulating angiogenic-osteogenic
      coupling. We also demonstrate that genetic ablation of Phd2 and Phd3 was
      sufficient to protect ovariectomized mice against bone loss without disrupting
      hematopoietic homeostasis. Importantly, we identify OPG as a HIF target gene
      capable of directing osteoblast-mediated osteoclastogenesis to regulate bone
      homeostasis. Here, we show that coordinated activation of specific PHD isoforms
      fine-tunes the osteoblastic response to hypoxia, thereby directing two important
      aspects of bone physiology: cross-talk between osteoblasts and osteoclasts and
      angiogenic-osteogenic coupling. 

PMID- 25846798
TI  - Cytotoxic response of platinum-coated gold nanorods in human breast cancer cells
      at very low exposure levels.
AB  - Because of unique optical behavior gold nanorods (GNRs) have attracted attention
      for the application in biomedical field such as bio-sensing, bio-imaging and
      hyperthermia. However, toxicological response of GNRs is controversial due to
      their different surface coating. Therefore, a comprehensive knowledge about
      toxicological profile of GNRs is necessary before their biomedical applications.
      First time, we investigated the toxic response of GNRs coated with platinum (GNRs
      Pt) in human breast carcinoma (MCF-7) cells. Platinum coating further improves
      the optical and catalytic properties of GNRs. Assays such as 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT), neutral red uptake
      (NRU) and lactate dehydroganase (LDH) assays have shown that GNRs-Pt induced
      cytotoxicity at very low exposure levels (0.1-0.8 MUg mL-1 ). Accumulation of
      cells in SubG1 phase and low mitochondrial membrane potential (JC-1 probe) in
      treated cells suggest that GNRs-Pt induced cell death via apoptotic pathway.
      Quantitative real-time PCR data demonstrated that mRNA expression of apoptotic
      genes (bax, caspase-3 and caspase-9) were up-regulated while anti-apoptotic gene
      bcl-2 was down-regulated in cells exposed to GNRs-Pt. We further observed the
      higher activity of caspase-3 and caspase-9 enzymes in GNRs-Pt treated cells
      supporting mRNA data. Moreover, N-acetyl cysteine (NAC) significantly attenuated
      the ROS generation and cytotoxicity induced by GNRs-Pt in MCF-7 cells suggesting
      that ROS might plays a crucial role in GNRs-Pt induced toxicity. This study warns
      of possible toxicity of GNRs even at very low exposure levels. Further
      investigations needed to explore potential mechanisms of this low dose toxicity
      phenomenon. (c) 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1344-1356, 2016.

PMID- 25846799
TI  - Introduction to Special Series: Deconstructing chronic low back pain in the older
      adult: shifting the paradigm from the spine to the person.

PMID- 25846797
TI  - Regulation of early T-lineage gene expression and developmental progression by
      the progenitor cell transcription factor PU.1.
AB  - The ETS family transcription factor PU.1 is essential for the development of
      several blood lineages, including T cells, but its function in intrathymic T-cell
      precursors has been poorly defined. In the thymus, high PU.1 expression persists
      through multiple cell divisions in early stages but then falls sharply during T
      cell lineage commitment. PU.1 silencing is critical for T-cell commitment, but it
      has remained unknown how PU.1 activities could contribute positively to T-cell
      development. Here we employed conditional knockout and modified antagonist PU.1
      constructs to perturb PU.1 function stage-specifically in early T cells. We show
      that PU.1 is needed for full proliferation, restricting access to some non-T
      fates, and controlling the timing of T-cell developmental progression such that
      removal or antagonism of endogenous PU.1 allows precocious access to T-cell
      differentiation. Dominant-negative effects reveal that this repression by PU.1 is
      mediated indirectly. Genome-wide transcriptome analysis identifies novel targets
      of PU.1 positive and negative regulation affecting progenitor cell signaling and
      cell biology and indicating distinct regulatory effects on different subsets of
      progenitor cell transcription factors. Thus, in addition to supporting early T
      cell proliferation, PU.1 regulates the timing of activation of the core T-lineage
      developmental program. 

PMID- 25846800
TI  - A general catalytic reaction sequence to access alkaloid-inspired indole
      polycycles.
AB  - A catalytic two-step reaction sequence was developed to access a range of complex
      heterocyclic frameworks based on biorelevant indole/oxindole scaffolds. The
      reaction sequence includes catalytic Pictet-Spengler cyclization followed by
      Au(I) catalyzed intramolecular hydroamination of acetylenes. A related cascade
      polycyclization of a designed beta-carboline embodying a 1,5-enyne group yields
      the analogues of the alkaloid harmicine.

PMID- 25846801
TI  - The effect of various morphine weaning regimens on the sequelae of opioid
      tolerance involving physical dependency, anxiety and hippocampus cell
      neurodegeneration in rats.
AB  - Chronic consumption of morphine induces physical dependency, anxiety, and
      neurodegeneration. In this study, morphine on its own has been used for the
      management of morphine-induced dependency, oxidative stress, and apoptosis. Forty
      eight male rats were randomly divided into six groups. Rats in groups 1-5 were
      made morphine dependent by an increasing manner of morphine for 7 days (15-45
      mg/kg). For the next 14 days, morphine was administered using the following
      regimen: (i) once daily 45 mg/kg (positive controls), (ii) the same dose at
      additional intervals (6 h longer than the previous intervals each time), (iii) 45
      mg/kg of morphine at irregular intervals like of 12, 24, 36 h, (iv) decreasing
      dose once daily (every time 2.5 mg/kg less than the former dosage). Group 5
      received 45 mg/kg of morphine and 10 mg/kg of SOD mimetic agent (M40401)
      injection per day. Group 6 (negative control) received saline solution only. On
      day 22, all animals received naloxone (3 mg/kg) and their Total Withdrawal Index
      (TWI) and blood cortisol levels were measured. After drug treatment, hippocampus
      cells were isolated, and oxidative, antioxidative, and apoptotic factors were
      evaluated. Various regimens of morphine reduced TWI, cortisol levels, Bax
      activity, caspase-3, caspase-9, TNF-alpha, and IL-1beta and lipid peroxidation.
      In all treatment groups, GSH level, superoxide dismutase, glutathione peroxidase,
      and Bcl-2 activity were significantly increased. Furthermore, SOD mimetic agent c
      diminished morphine effect on SOD activity. Thus, varying the dosage regimen of
      morphine can reduce the severity of morphine-induced dependency and
      neurodegeneration.

PMID- 25846802
TI  - A novel approach to tracer-kinetic modeling for (macromolecular) dynamic contrast
      enhanced MRI.
AB  - PURPOSE: To develop a novel tracer-kinetic modeling approach for multi-agent
      dynamic contrast-enhanced MRI (DCE-MRI) that facilitates separate estimation of
      parameters characterizing blood flow and microvascular permeability within one
      individual. METHODS: Monte Carlo simulations were performed to investigate the
      performance of the constrained multi-agent model. Subsequently, multi-agent DCE
      MRI was performed on tumor-bearing mice (n = 5) on a 7T Bruker scanner on three
      measurement days, in which two dendrimer-based contrast agents having high and
      intermediate molecular weight, respectively, along with gadoterate meglumine,
      were sequentially injected within one imaging session. Multi-agent data were
      simultaneously fit with the gamma capillary transit time model. Blood flow, mean
      capillary transit time, and bolus arrival time were constrained to be identical
      between the boluses, while extraction fractions and washout rate constants were
      separately determined for each agent. RESULTS: Simulations showed that
      constrained multi-agent model regressions led to less uncertainty and bias in
      estimated tracer-kinetic parameters compared with single-bolus modeling. The
      approach was successfully applied in vivo, and significant differences in the
      extraction fraction and washout rate constant between the agents, dependent on
      their molecular weight, were consistently observed. CONCLUSION: A novel multi
      agent tracer-kinetic modeling approach that enforces self-consistency of model
      parameters and can robustly characterize tumor vascular status was demonstrated.

PMID- 25846804
TI  - Is cholesterol good or bad for your brain?--NMDARs have a say.

PMID- 25846803
TI  - Breaking the ice! Predictors about communication between nonresident African
      American fathers and sons about sex.
AB  - BACKGROUND AND PURPOSE: Research on communication between resident and
      nonresident African American fathers and their sons about sex has been
      understudied. The purpose of this study is to determine the influence of
      parenting variables, specifically, racial socialization and father involvement on
      nonresident African American father-son communication about sex. METHODS: Data
      for this study are from the Fathers and Sons Project. This intervention study is
      designed to enhance relationships between nonresident African American fathers
      and their 8-12 year old sons and to prevent risky health behaviors among sons.
      The present study is based on 345 African American boys who completed baseline
      face-to-face interviews. The average age of the sons was 10.2 years old (SD =
      1.4), with an average of two siblings (SD = 1.53). RESULTS: Age and sons'
      perceptions of more parental monitoring by their fathers were predictive of
      increased communication about sex. Racial socialization messages explained
      additional variance in communication about sex above other parenting variables
      and controls. IMPLICATIONS FOR PRACTICE: Findings suggest when working with
      African American families, providers who counsel parents, and in particular
      provide outreach to fathers regarding communication about sex, are in a unique
      position to enhance parenting communication skills about sexuality.

PMID- 25846805
TI  - Health anxiety and hypochondriasis in the light of DSM-5.
AB  - BACKGROUND: In the DSM-5, the diagnosis of hypochondriasis was replaced by two
      new diagnositic entities: somatic symptom disorder (SSD) and illness anxiety
      disorder (IAD). Both diagnoses share high health anxiety as a common criterion,
      but additonal somatic symptoms are only required for SSD but not IAD. DESIGN: Our
      aim was to provide empirical evidence for the validity of these new diagnoses
      using data from a case-control study of highly health-anxious (n = 96), depressed
      (n = 52), and healthy (n = 52) individuals. RESULTS: The individuals originally
      diagnosed as DSM-IV hypochondriasis predominantly met criteria for SSD (74%) and
      rarely for IAD (26%). Individuals with SSD were more impaired, had more often
      comorbid panic and generalized anxiety disorders, and had more medical
      consultations as those with IAD. Yet, no significant differences were found
      between SSD and IAD with regard to levels of health anxiety, other
      hypochondriacial characteristics, illness behavior, somatic symptom attributions,
      and physical concerns, whereas both groups differed significantly from clinical
      and healthy controls in all of these variables. CONCLUSION: These results do not
      support the proposed splitting of health anxiety/hypochondriasis into two
      diagnoses. Further validation studies with larger samples and additional control
      groups are warranted to prove the validity of the new diagnoses.

PMID- 25846806
TI  - Reliability and validity of the Duncan-Ely test for assessing rectus femoris
      spasticity in patients with cerebral palsy.
AB  - AIM: The aim of this study was to clarify the method of the Duncan-Ely test and
      to estimate its interobserver reliability and validity by comparing it with three
      dimensional gait analysis (3DGA). METHOD: This study included 36 consecutive
      ambulatory patients with cerebral palsy (CP) who underwent preoperative 3DGA. The
      Duncan-Ely test was performed during three different velocities (slow, gravity,
      and fast). The interobserver reliability was assessed by three examiners. The
      results of the test were compared with kinematic variables derived from the gait
      analysis to assess the sensitivity and specificity of the test. The cut-off value
      was determined at the point of trade-off between the highest sensitivity and
      specificity. RESULTS: The intraclass correlation coefficient measuring
      interobserver reliability of the Duncan-Ely test was greatest during fast
      velocity (0.819). The sensitivity and specificity of the test during gravity
      velocity for knee range of motion total were 63.0% and 100% respectively, with a
      cut-off value of 78.3 degrees . The sensitivity and specificity of the test
      during fast velocity for knee range of motion total were 66.7% and 100%
      respectively, with a cut-off value of 65 degrees . INTERPRETATION: The Duncan-Ely
      test shows excellent reliability in fast knee-flexion velocity, and good
      sensitivity and specificity compared with 3DGA during physical examination as a
      preoperative assessment of rectus femoris spasticity in patients with CP.

PMID- 25846808
TI  - Effects of 50 Hz magnetic fields on gap junctional intercellular communication in
      NIH3T3 cells.
AB  - The present study focused on gap junctional intercellular communication (GJIC) as
      a target for biological effects of extremely low-frequency (ELF) magnetic field
      (MF) exposure. Fluorescence recovery after photobleaching microscopy (FRAP) was
      used to visualize diffusion of a fluorescent dye between NIH3T3 fibroblasts
      through gap junctions. The direct effect of 24 h exposure to 50 Hz MF at 0.4 or 1
      mT on GJIC function was assessed in one series of experiments. The potential
      synergism of MF with an inhibitor of GJIC, phorbol ester (TPA), was studied in
      another series by observing FRAP when NIH3T3 cells were incubated with TPA for 1
      h following 24 h exposure to MF. In contrast to other reports of ELF-MF effects
      on GJIC, under our experimental conditions we observed neither direct inhibition
      of GJIC nor synergism with TPA-induced inhibition from 50 Hz MF exposures.

PMID- 25846807
TI  - Saprolegnia diclina IIIA and S. parasitica employ different infection strategies
      when colonizing eggs of Atlantic salmon, Salmo salar L.
AB  - Here, we address the morphological changes of eyed eggs of Atlantic salmon, Salmo
      salar L. infected with Saprolegnia from a commercial hatchery and after
      experimental infection. Eyed eggs infected with Saprolegnia spp. from 10 Atlantic
      salmon females were obtained. Egg pathology was investigated by light and
      scanning electron microscopy. Eggs from six of ten females were infected with S.
      parasitica, and two females had infections with S. diclina clade IIIA; two
      Saprolegnia isolates remained unidentified. Light microscopy showed S. diclina
      infection resulted in the chorion in some areas being completely destroyed,
      whereas eggs infected with S. parasitica had an apparently intact chorion with
      hyphae growing within or beneath the chorion. The same contrasting pathology was
      found in experimentally infected eggs. Scanning electron microscopy revealed that
      S. parasitica grew on the egg surface and hyphae were found penetrating the
      chorion of the egg, and re-emerging on the surface away from the infection site.
      The two Saprolegnia species employ different infection strategies when colonizing
      salmon eggs. Saprolegnia diclina infection results in chorion destruction, while
      S. parasitica penetrates intact chorion. We discuss the possibility these
      infection mechanisms representing a necrotrophic (S. diclina) vs. a facultative
      biotrophic strategy (S. parasitica). 

PMID- 25846810
TI  - Diagnosis of truncus arteriosus in first trimester of pregnancy using
      transvaginal four-dimensional color Doppler ultrasound.

PMID- 25846809
TI  - Beta-interferon exposure and onset of secondary progressive multiple sclerosis.
AB  - BACKGROUND AND PURPOSE: Beta-interferons (IFNbeta) are the most widely prescribed
      drugs for patients with multiple sclerosis (MS). However, whether or not
      treatment with IFNbeta can delay secondary progressive MS (SPMS) onset remains
      unknown. Our aim was to examine the association between IFNbeta exposure and SPMS
      onset in patients with relapsing-remitting MS (RRMS). METHODS: A retrospective
      cohort study using British Columbia (Canada) population-based clinical and health
      administrative data (1985-2008) was conducted. RRMS patients treated with IFNbeta
      (n = 794) were compared with untreated contemporary (n = 933) and historical (n =
      837) controls. Cohort entry was the first clinic visit during which patients
      became eligible for IFNbeta treatment (baseline). The outcome was time from
      baseline to SPMS onset. Cox regression models with IFNbeta as a time-dependent
      exposure were adjusted for sex, and baseline age, disease duration, disability,
      *socioeconomic status and *comorbidities (*available for the contemporary cohorts
      only). Additional analyses included propensity score adjustment. RESULTS: The
      median follow-up for the IFNbeta-treated, untreated contemporary and historical
      controls were 5.7, 3.7 and 7.3 years, and the proportions of patients reaching
      SPMS were 9.2%, 11.8% and 32.9%, respectively. After adjustment for confounders,
      IFNbeta exposure was not associated with the risk of reaching SPMS when either
      the contemporary or the historical untreated cohorts were considered (hazard
      ratio 1.07; 95% confidence interval 0.93-1.48, and hazard ratio 1.04; 95%
      confidence interval 0.74-1.46, respectively). Further adjustments and the
      propensity score yielded results consistent with the main analysis. CONCLUSIONS:
      Amongst patients with RRMS, use of IFNbeta was not associated with a delayed
      onset of SPMS.

PMID- 25846811
TI  - Negative regulation of the LKB1/AMPK pathway by ERK in human acute myeloid
      leukemia cells.
AB  - Adenosine monophosphate-activated protein kinase (AMPK) is a sensor for cellular
      energy status. When the cellular energy level is decreased, AMPK is activated and
      functions to suppress energy-consuming processes, including protein synthesis.
      Recently, AMPK has received attention as an attractive molecular target for
      cancer therapy. Several studies have revealed that the activation of AMPK by
      chemical stimulators, such as metformin, induces apoptosis in a variety of
      hematologic malignant cells. From another perspective, these results suggest that
      the function of AMPK is impaired in hematologic tumor cells. However, the precise
      mechanisms by which this impairment occurs are not well understood. In melanoma
      cells, oncogenic BRAF constitutively activates the extracellular signal-regulated
      kinase (ERK) pathway and phosphorylates liver kinase B1, an upstream activator of
      5' adenosine monophosphate-activated protein kinase (AMPK), resulting in the
      inactivation of liver kinase B1 and AMPK. In this study, we analyzed whether ERK
      is involved in the suppression of AMPK activity using established and primary
      human leukemia cells. We found an inverse correlation between the intensity of
      ERK activity and the degree of AMPK activation after stimulation with either
      glucose deprivation or metformin. We also found that the inhibition of ERK
      activity by U0126 restored AMPK activation after metformin treatment.
      Furthermore, a combined treatment with metformin and U0126 enhanced the
      antileukemic activity of metformin. Importantly, metformin induced ERK activation
      by suppressing the protein levels of dual specificity phosphatase 6, a negative
      regulator of ERK. This crosstalk between AMPK and ERK could diminish the
      antileukemic activity of metformin. Taken together, our present observations
      suggest a novel therapeutic strategy for improving the efficacy of metformin in
      treating leukemia. 

PMID- 25846812
TI  - Transcatheter stenting of the systemic-to-pulmonary artery shunt: A 7-year
      experience from a single tertiary center.
AB  - BACKGROUND: Systemic-to-pulmonary artery shunt (SPS) dysfunction can be
      deleterious in shunt dependent patients and traditionally have undergone surgical
      revision. Data on transcatheter stenting of SPS is limited. We sought to evaluate
      feasibility, safety and outcomes of stenting SPS. METHODS: Retrospective review
      of all patients who underwent transcatheter SPS stenting from 1/2006 to 12/2013.
      RESULTS: Of 229 surgically implanted SPS, 25 transcatheter stent interventions
      were performed in 22 patients. The majority had pulmonary atresia (n = 9) or HLHS
      (n = 10). Their median age was 4 ms (range 10 days to 4 years) and median weight
      4.9 kg (range 3-14). Nine had a central and 15 had a BT shunt with a median shunt
      size of 3.75 mm (range 3-6). The interval from shunt placement to intervention
      was 1.9 ms (range 4 days-3.8 years). The indication for intervention was
      increasing cyanosis in10 patients and delaying final repair in 9. Two patients
      were on ECMO at the time of intervention. The median shunt diameter increased
      from 2.3 to 4.1 mm and oxygen saturation from 72 to 85% (P < 0.001). No intra
      procedural complications were encountered. One patient died from aspiration
      (autopsy demonstrated a patent shunt), 13 progressed to repair or next stage, 6
      remain palliated with shunts as they are deemed unfit for the next stage and 2
      are awaiting surgery. CONCLUSIONS: Stenting of systemic to pulmonary artery shunt
      is a safe and effective procedure and avoids surgical re-intervention. It can be
      performed both as a rescue procedure in patients with acute shunt occlusion and
      as an elective procedure to palliate patients not yet suitable for subsequent
      corrective or staged repair.

PMID- 25846813
TI  - Prognostic value of epidermal growth factor receptor amplification and EGFRvIII
      in glioblastoma: meta-analysis.
AB  - OBJECTIVES: Epidermal growth factor receptor (EGFR) gene amplification and the
      EGFRvIII mutation may have prognostic value in patients with glioblastoma. This
      meta-analysis was to determine whether EGFR gene amplification or the EGFRvIII
      mutation are predictors of survival in patients with glioblastoma and anaplastic
      astrocytoma. MATERIALS AND METHODS: Medline, the Cochrane Central Register of
      Controlled Trials, EMBASE, and Google Scholar databases were searched until July
      31, 2014. Studies were selected for inclusion in the analysis if they included
      patients with anaplastic astrocytoma and/or glioblastoma, EGFR and/or EGFRvIII
      mutation status was reported, and overall survival (OS) data were reported.
      RESULTS: Of 113 articles initially identified, only eight contained data with
      respect to the outcome of interest and were included in the meta-analysis. The
      number of cases ranged from 14 to 268, and the majority of patients were 60 or
      more years of age. There was no significant difference in OS between EGFR
      amplification-positive and EGFR amplification-negative glioblastoma patients
      (pooled hazard ratio [HR] = 1.101, 95% confidence interval [CI] 0.845, 1.434, P =
      0.475) or anaplastic astrocytoma patients (pooled HR = 1.455, 95% CI 0.852,
      2.482, P = 0.169). There was no significant difference in OS between EGFRvIII
      positive and EGFRvIII-negative glioblastoma patients (pooled HR = 1.321, 95% CI:
      0.881-1.981, P = 0.178). Significant heterogeneity existed between the studies,
      and the significance changed when the analysis was performed with studies removed
      in turn. CONCLUSIONS: There is insufficient evidence that either EGFR
      amplification or the EGFRvIII mutation has prognostic value in patients with
      glioblastoma.

PMID- 25846814
TI  - ULTRASONOGRAPHIC FEATURES OF CANINE GASTROINTESTINAL STROMAL TUMORS COMPARED TO
      OTHER GASTROINTESTINAL SPINDLE CELL TUMORS.
AB  - Canine gastrointestinal stromal tumors (GISTs) are a recent subtype of
      gastrointestinal spindle cell tumor recognized with the increasing use of
      immunohistochemistry. To our knowledge, no imaging features have been described
      in immunostochemically confirmed canine GISTs. The objective of this
      retrospective, cross-sectional study was to describe ultrasonographic features of
      canine GISTs compared with other spindle cell tumors. Thirty-seven dogs with an
      ultrasonographically visible gastrointestinal mass and a histopathologic
      diagnosis of spindle cell neoplasia were examined. Immunohistochemistry staining
      was performed for retrieved tissue samples to further differentiate the tumor
      type and each sample was interpreted by a single veterinary pathologist.
      Ultrasonographic features recorded examined included mass echogenicity,
      homogeneity, presence of cavitation, layer of origin, bowel wall symmetry, and
      loss of wall layering, location, size, vascularity, and evidence of perforation
      or ulceration. Tumor types included 19 GISTs, eight leiomyosarcomas, six
      leiomyomas, and four nonspecified sarcomas. Gastrointestinal stromal tumors were
      significantly more likely to be associated (P < 0.03) with abdominal effusion
      than other tumor types. There was overlap between the anatomical locations of all
      tumors types with the exception of the cecum where all eight tumors identified
      were GISTs. Besides location, there were no unique ultrasound features of GISTs
      that would allow distinction from other gastrointestinal spindle cell tumors.
      Similar to previous studies, GISTs appeared to be the most common spindle cell
      tumor associated with the cecum in our sample of dogs. The high frequency of
      abdominal effusion with GIST's was of unknown etiology could possibly have been
      due to septic peritonitis.

PMID- 25846815
TI  - Triple Raman Label-Encoded Gold Nanoparticle Trimers for Simultaneous Heavy Metal
      Ion Detection.
AB  - Here, a triple Raman label-encoded gold nanoparticle (AuNP) trimer is fabricated
      for heavy metal ion detection. In the presence of target ions, the gold
      nanoparticles modified with different Raman labels are assembled into trimers and
      produce different enhancements of Raman reporters, which are functionalized as
      Raman probes for simultaneous silver and mercury ion detection. Under optimized
      conditions, the limits of detection of Ag(+) and Hg(2+) reach 8.42 * 10(-12) and
      16.78 * 10(-12) m, respectively. 

PMID- 25846816
TI  - Urinary incontinence persisting after childbirth: extent, delivery history, and
      effects in a 12-year longitudinal cohort study.
AB  - OBJECTIVE: To investigate the extent of persistent urinary incontinence (UI) 12
      years after birth, and association with delivery-mode history and other factors.
      DESIGN: Twelve-year longitudinal cohort study. SETTING: Maternity units in
      Aberdeen, Birmingham, and Dunedin. POPULATION: Women who returned questionnaires
      3 months and 12 years after index birth. METHODS: Data on all births over a
      period of 12 months were obtained from the units and then women were contacted by
      post. MAIN OUTCOME MEASURE: Persistent UI reported at 12 years, with one or more
      previous contact. RESULTS: Of 7879 women recruited at 3 months, 3763 (48%)
      responded at 12 years, with 2944 also having responded at 6 years; non-responders
      had similar obstetric characteristics. The prevalence of persistent UI was 37.9%
      (1429/3763). Among those who had reported UI at 3 months, 76.4% reported it at 12
      years. Women with persistent UI had lower SF12 quality of life scores. Compared
      with having only spontaneous vaginal deliveries (SVDs), women who delivered
      exclusively by caesarean section were less likely to have persistent UI (odds
      ratio, OR 0.42, 95% CI 0.33-0.54). This was not the case in women who had a
      combination of caesarean section and SVD births (OR 1.01, 95% CI 0.78-1.30).
      Older age at first birth, greater parity, and overweight/obesity were associated
      with persistent UI. Of 54 index primiparae with UI before pregnancy, 46 (85.2%)
      had persistent UI. CONCLUSIONS: This study, demonstrating that UI persists to 12
      years in about three-quarters of women, and that risk was only reduced with
      caesarean section if women had no other delivery mode, has practice implications.
      TWEETABLE ABSTRACT: A longitudinal study of 3763 women showed a prevalence of
      persistent UI 12 years after birth of 37.9%.

PMID- 25846817
TI  - Underutilisation of synchronised cardioversion.

PMID- 25846818
TI  - Factors Contributing to Sexual Violence at Selected Schools for Learners with
      Mild Intellectual Disability in South Africa.
AB  - BACKGROUND: This paper reports part of the findings of a study which exposed
      sexual violence in schools for learners with mild intellectual disability in
      South Africa. Special attention was paid on factors contributing to such a
      problem. METHODS: Data were collected using focus groups and individual
      interviews with 16 learners with mild intellectual disability at two special
      schools in South Africa. This was followed by individual interviews with the
      school nurse and social worker, and an analysis of schools' books of incidents.
      RESULTS: Factors contributing to sexual violence at schools for learners with
      mild intellectual disability included: (i) peer pressure, (ii) concealment of
      reported incidents of sexual violence, (iii) unsupervised areas linked to schools
      and (iv) arranged relationships. CONCLUSION: The following suggestions are put
      forth: (i) awareness programmes, (ii) sensitization of teachers about the
      consequences and prevention of sexual violence, (iii) boundaries within which the
      arranged relationship occurs, (iv) intensification of sexuality education and (v)
      supervision around the school premises.

PMID- 25846819
TI  - Korean Red Ginseng and Ginsenoside-Rb1/-Rg1 Alleviate Experimental Autoimmune
      Encephalomyelitis by Suppressing Th1 and Th17 Cells and Upregulating Regulatory T
      Cells.
AB  - The effects of Korean red ginseng extract (KRGE) on autoimmune disorders of the
      nervous system are not clear. We investigated whether KRGE has a beneficial
      effect on acute and chronic experimental autoimmune encephalomyelitis (EAE).
      Pretreatment (daily from 10 days before immunization with myelin basic protein
      peptide) with KRGE significantly attenuated clinical signs and loss of body
      weight and was associated with the suppression of spinal demyelination and glial
      activation in acute EAE rats, while onset treatment (daily after the appearance
      of clinical symptoms) did not. The suppressive effect of KRGE corresponded to the
      messenger RNA (mRNA) expression of proinflammatory cytokines (tumor necrosis
      factor-alpha [TNF-alpha] and interleukin [IL]-1beta), chemokines (RANTES,
      monocyte chemotactic protein-1 [MCP-1], and macrophage inflammatory protein
      1alpha [MIP-1alpha]), adhesion molecules (intercellular adhesion molecule-1 [ICAM
      1], vascular cell adhesion molecule-1 [VCAM-1], and platelet endothelial cell
      adhesion molecule [PECAM-1]), and inducible nitric oxide synthase in the spinal
      cord after immunization. Interestingly, in acute EAE rats, pretreatment with KRGE
      significantly reduced the population of CD4(+), CD4(+)/IFN-gamma(+), and
      CD4(+)/IL-17(+) T cells in the spinal cord and lymph nodes, corresponding to the
      downregulation of mRNA expression of IFN-gamma, IL-17, and IL-23 in the spinal
      cord. On the other hand, KRGE pretreatment increased the population of
      CD4(+)/Foxp3(+) T cells in the spinal cord and lymph nodes of these rats,
      corresponding to the upregulation of mRNA expression of Foxp3 in the spinal cord.
      Interestingly, intrathecal pretreatment of rats with ginsenosides (Rg1 and Rb1)
      significantly decreased behavioral impairment. These results strongly indicate
      that KRGE has a beneficial effect on the development and progression of EAE by
      suppressing T helper 1 (Th1) and Th17 T cells and upregulating regulatory T
      cells. Additionally, pre- and onset treatment with KRGE alleviated neurological
      impairment of myelin oligodendrocyte glycoprotein(35-55)-induced mouse model of
      chronic EAE. These results warrant further investigation of KRGE as preventive or
      therapeutic strategies for autoimmune disorders, such as multiple sclerosis.

PMID- 25846821
TI  - A land plant-specific thylakoid membrane protein contributes to photosystem II
      maintenance in Arabidopsis thaliana.
AB  - The structure and function of photosystem II (PSII) are highly susceptible to
      photo-oxidative damage induced by high-fluence or fluctuating light. However,
      many of the mechanistic details of how PSII homeostasis is maintained under
      photoinhibitory light remain to be determined. We describe an analysis of the
      Arabidopsis thaliana gene At5g07020, which encodes an unannotated integral
      thylakoid membrane protein. Loss of the protein causes altered PSII function
      under high-irradiance light, and hence it is named 'Maintenance of PSII under
      High light 1' (MPH1). The MPH1 protein co-purifies with PSII core complexes and
      co-immunoprecipitates core proteins. Consistent with a role in PSII structure,
      PSII complexes (supercomplexes, dimers and monomers) of the mph1 mutant are less
      stable in plants subjected to photoinhibitory light. Accumulation of PSII core
      proteins is compromised under these conditions in the presence of translational
      inhibitors. This is consistent with the hypothesis that the mutant has enhanced
      PSII protein damage rather than defective repair. These data are consistent with
      the distribution of the MPH1 protein in grana and stroma thylakoids, and its
      interaction with PSII core complexes. Taken together, these results strongly
      suggest a role for MPH1 in the protection and/or stabilization of PSII under high
      light stress in land plants.

PMID- 25846820
TI  - (S)-Lacosamide Binding to Collapsin Response Mediator Protein 2 (CRMP2) Regulates
      CaV2.2 Activity by Subverting Its Phosphorylation by Cdk5.
AB  - The neuronal circuit remodels during development as well as in human
      neuropathologies such as epilepsy. Neurite outgrowth is an obligatory step in
      these events. We recently reported that alterations in the phosphorylation state
      of an axon specification/guidance protein, the collapsin response mediator
      protein 2 (CRMP2), play a major role in the activity-dependent regulation of
      neurite outgrowth. We also identified (S)-LCM, an inactive stereoisomer of the
      clinically used antiepileptic drug (R)-LCM (Vimpat(r)), as a novel tool for
      preferentially targeting CRMP2-mediated neurite outgrowth. Here, we investigated
      the mechanism by which (S)-LCM affects CRMP2 phosphorylation by two key kinases,
      cyclin-dependent kinase 5 (Cdk5) and glycogen synthase kinase 3beta (GSK-3beta).
      (S)-LCM application to embryonic cortical neurons resulted in reduced levels of
      Cdk5- and GSK-3beta-phosphorylated CRMP2. Mechanistically, (S)-LCM increased
      CRMP2 binding to both Cdk5- and GSK-3beta without affecting binding of CRMP2 to
      its canonical partner tubulin. Saturation transfer difference nuclear magnetic
      resonance (STD NMR) and differential scanning fluorimetry (DSF) experiments
      demonstrated direct binding of (S)-LCM to CRMP2. Using an in vitro luminescent
      kinase assay, we observed that (S)-LCM specifically inhibited Cdk5-mediated
      phosphorylation of CRMP2. Cross-linking experiments and analytical
      ultracentrifugation showed no effect of (S)-LCM on the oligomerization state of
      CRMP2. The increased association between Cdk5-phosphorylated CRMP2 and CaV2.2 was
      reduced by (S)-LCM in vitro and in vivo. This reduction translated into a
      decrease of calcium influx via CaV2.2 in (S)-LCM-treated neurons compared to
      controls. (S)-LCM, to our knowledge, is the first molecule described to directly
      inhibit CRMP2 phosphorylation and may be useful for delineating CRMP2-facilitated
      functions. 

PMID- 25846822
TI  - Capillary growth, ultrastructure remodelling and exercise training in skeletal
      muscle of essential hypertensive patients.
AB  - AIM: The aim was to elucidate whether essential hypertension is associated with
      altered capillary morphology and density and to what extent exercise training can
      normalize these parameters. METHODS: To investigate angiogenesis and capillary
      morphology in essential hypertension, muscle biopsies were obtained from m.
      vastus lateralis in subjects with essential hypertension (n = 10) and
      normotensive controls (n = 11) before and after 8 weeks of aerobic exercise
      training. Morphometry was performed after transmission electron microscopy, and
      protein levels of several angioregulatory factors were determined. RESULTS: At
      baseline, capillary density and capillary-to-fibre ratio were not different
      between the two groups. However, the hypertensive subjects had 9% lower capillary
      area (12.7 +/- 0.4 vs. 13.9 +/- 0.2 MUm(2)) and tended to have thicker capillary
      basement membranes (399 +/- 16 vs. 358 +/- 13 nm; P = 0.094) than controls.
      Protein expression of vascular endothelial growth factor (VEGF), VEGF receptor-2
      and thrombospondin-1 were similar in normotensive and hypertensive subjects, but
      tissue inhibitor of matrix metalloproteinase was 69% lower in the hypertensive
      group. After training, angiogenesis was evident by 15% increased capillary-to
      fibre ratio in the hypertensive subjects only. Capillary area and capillary lumen
      area were increased by 7 and 15% in the hypertensive patients, whereas capillary
      basement membrane thickness was decreased by 17% (P < 0.05). VEGF expression
      after training was increased in both groups, whereas VEGF receptor-2 was
      decreased by 25% in the hypertensive patients(P < 0.05). CONCLUSION: Essential
      hypertension is associated with decreased lumen area and a tendency for increased
      basement membrane thickening in capillaries of skeletal muscle. Exercise training
      may improve the diffusion conditions in essential hypertension by altering
      capillary structure and capillary number.

PMID- 25846823
TI  - Development of laser desorption imaging mass spectrometry methods to investigate
      the molecular composition of latent fingermarks.
AB  - For a century, fingermark analysis has been one of the most important and common
      methods in forensic investigations. Modern chemical analysis technologies have
      added the potential to determine the molecular composition of fingermarks and
      possibly identify chemicals a suspect may have come into contact with.
      Improvements in analytical detection of the molecular composition of fingermarks
      is therefore of great importance. In this regard, matrix-assisted laser
      desorption ionization (MALDI) and laser desorption ionization (LDI) imaging mass
      spectrometry (IMS) have proven to be useful technologies for fingermark analysis.
      In these analyses, the choice of ionizing agent and its mode of deposition are
      critical steps for the identification of molecular markers. Here we propose two
      novel and complementary IMS approaches for endogenous and exogenous substance
      detection in fingermarks: sublimation of 2-mercaptobenzothiazol (2-MBT) matrix
      and silver sputtering. 

PMID- 25846824
TI  - Standard assessments of frailty are validated predictors of mortality in
      hospitalized patients with cirrhosis.
AB  - The risk of morbidity and mortality for hospitalized patients with cirrhosis is
      high and incompletely captured by conventional indices. We sought to evaluate the
      predictive role of frailty in an observational cohort study of inpatients with
      decompensated cirrhosis between 2010 and 2013. The primary outcome was 90-day
      mortality. Secondary outcomes included discharge to a rehabilitation hospital, 30
      day readmission, and length of stay. Frailty was assessed with three metrics:
      activities of daily living (ADL), the Braden Scale, and the Morse fall risk
      score. A predictive model was validated by randomly dividing the population into
      training and validation cohorts: 734 patients were admitted 1358 times in the
      study period. The overall 90-day mortality was 18.3%. The 30-day readmission rate
      was 26.6%, and the rate of discharge to a rehabilitation facility was 14.3%.
      Adjusting for sex, age, Model for End-Stage Liver Disease, sodium, and Charlson
      index, the odds ratio for the effect of an ADL score of less than 12 of 15 on
      mortality is 1.83 (95% confidence interval [CI] 1.05-3.20). A predictive model
      for 90-day mortality including ADL and Braden Scale yielded C statistics of 0.83
      (95% CI 0.80-0.86) and 0.77 (95% CI 0.71-0.83) in the derivation and validation
      cohorts, respectively. Discharge to a rehabilitation hospital is predicted by
      both the ADL (<12) and Braden Scale (<16), with respective adjusted odds ratios
      of 3.78 (95% CI 1.97-7.29) and 6.23 (95% CI 2.53-15.4). Length of stay was
      associated with the Braden Scale (<16) (hazard ratio = 0.63, 95% CI 0.44-0.91).
      No frailty measure was associated with 30-day readmission. CONCLUSIONS: Readily
      available, standardized measures of frailty predict 90-day mortality, length of
      stay, and rehabilitation needs for hospitalized patients with cirrhosis.

PMID- 25846825
TI  - The devil is in the details: genetic variation in introduced populations and its
      contributions to invasion.
AB  - The influence of genetic variation on invasion success has captivated researchers
      since the start of the field of invasion genetics 50 years ago. We review the
      history of work on this question and conclude that genetic variation-as surveyed
      with molecular markers-appears to shape invasion rarely. Instead, there is a
      significant disconnect between marker assays and ecologically relevant genetic
      variation in introductions. We argue that the potential for adaptation to
      facilitate invasion will be shaped by the details of genotypes affecting
      phenotypes, and we highlight three areas in which we see opportunities to make
      powerful new insights. (i) The genetic architecture of adaptive variation. Traits
      shaped by large-effect alleles may be strongly impacted by founder events yet
      more likely to respond to selection when genetic drift is strong. Large-effect
      loci may be especially relevant for traits involved in biotic interactions. (ii)
      Cryptic genetic variation exposed during invasion. Introductions have strong
      potential to uncover masked variation due to alterations in genetic and
      ecological environments. (iii) Genetic interactions during admixture of multiple
      source populations. As divergence among sources increases, positive followed by
      increasingly negative effects of admixture should be expected. Although generally
      hypothesized to be beneficial during invasion, admixture is most often reported
      among sources of intermediate divergence, supporting the possibility that
      incompatibilities among divergent source populations might be limiting their
      introgression. Finally, we note that these details of invasion genetics can be
      coupled with comparative demographic analyses to link genetic changes to the
      evolution of invasiveness itself.

PMID- 25846826
TI  - Effective Tuning of Ketocyanine Derivatives through Acceptor Substitution.
AB  - A series of ketocyanine derivatives possessing bis(diarylamino)fluorenyl donors
      and variable acceptors installed at the bridging carbon atom were synthesized to
      investigate how the electronic structure of the dye can be systemically tuned
      through stabilization of the cyanine-like character of the donor by increasing
      the acceptor strength. Analysis of the (1) H NMR spectra indicates that the
      "charge-separated" species dominates in these dyes, given that carbons possessing
      a positive or negative charge in the resonance structures of this state
      purposefully shift downfield or upfield, respectively, depending on the strength
      of the acceptor moiety. In DAA-Fl-PI, the acceptor strength and the gain of
      acceptor aromaticity indicates a predisposition of the separated state, indicated
      by asymmetry in the (1) H NMR spectrum, as well as uneven distribution of the
      HOMO on the fluorenyl donor. 

PMID- 25846827
TI  - Comment on the extraordinary career of Professor Dr Simon van Creveld.

PMID- 25846828
TI  - Distinct contribution of Toxoplasma gondii rhomboid proteases 4 and 5 to
      micronemal protein protease 1 activity during invasion.
AB  - Host cell entry by the Apicomplexa is associated with the sequential secretion of
      invasion factors from specialized apical organelles. Secretion of micronemal
      proteins (MICs) complexes by Toxoplasma gondii facilitates parasite gliding
      motility, host cell attachment and entry, as well as egress from infected cells.
      The shedding of MICs during these steps is mediated by micronemal protein
      proteases MPP1, MPP2 and MPP3. The constitutive activity of MPP1 leads to the
      cleavage of transmembrane MICs and is linked to the surface rhomboid protease 4
      (ROM4) and possibly to rhomboid protease 5 (ROM5). To determine their importance
      and respective contribution to MPP1 activity, in this study ROM4 and ROM5 genes
      were abrogated using Cre-recombinase and CRISPR-Cas9 nuclease, respectively, and
      shown to be dispensable for parasite survival. Parasites lacking ROM4
      predominantly engage in twirling motility and exhibit enhanced attachment and
      impaired invasion, whereas intracellular growth and egress is not affected. The
      substrates MIC2 and MIC6 are not cleaved in rom4-ko parasites, in contrast,
      intramembrane cleavage of AMA1 is reduced but not completely abolished. Shedding
      of MICs and invasion are not altered in the absence of ROM5; however, this
      protease responsible for the residual cleavage of AMA1 is able to cleave other
      AMA family members and exhibits a detectable contribution to invasion in the
      absence of ROM4. 

PMID- 25846829
TI  - A new method for studying population genetics of cyst nematodes based on Pool-Seq
      and genomewide allele frequency analysis.
AB  - Cyst nematodes are important agricultural pests responsible for billions of
      dollars of losses each year. Plant resistance is the most effective management
      tool, but it requires a close monitoring of population genetics. Current
      technologies for pathotyping and genotyping cyst nematodes are time-consuming,
      expensive and imprecise. In this study, we capitalized on the reproduction mode
      of cyst nematodes to develop a simple population genetic analysis pipeline based
      on genotyping-by-sequencing and Pool-Seq. This method yielded thousands of SNPs
      and allowed us to study the relationships between populations of different
      origins or pathotypes. Validation of the method on well-characterized populations
      also demonstrated that it was a powerful and accurate tool for population
      genetics. The genomewide allele frequencies of 23 populations of golden nematode,
      from nine countries and representing the five known pathotypes, were compared. A
      clear separation of the pathotypes and fine genetic relationships between and
      among global populations were obtained using this method. In addition to being
      powerful, this tool has proven to be very time- and cost-efficient and could be
      applied to other cyst nematode species. 

PMID- 25846830
TI  - Serum microRNAs as Potential Biomarkers of Juvenile Idiopathic Arthritis.
AB  - MicroRNAs (miRNAs) are non-coding RNAs that regulate gene expression of targeted
      mRNAs, which are important in the pathogenesis of autoimmune diseases. MiRNAs may
      have the potential to serve as biomarkers of disease. We evaluated serum levels
      of selected miRNAs and their associations with disease activity in juvenile
      idiopathic arthritis (JIA). Sera and peripheral blood leukocytes were collected
      from patients with JIA (8 systemic onset, 16 polyarthritis) and healthy controls.
      Levels of miR-16, miR-132, miR-146a, miR-155, and miR-223 were quantified. Levels
      of miR-223 in sera were significantly higher in patients in the active phase of
      systemic onset JIA than in controls. MiRNAs of peripheral blood leukocytes did
      not exhibit any difference between patients with JIA and controls. In both
      systemic onset JIA and polyarthritis patients, levels of miR-223 and miR-16
      correlated with erythrocyte sedimentation rate and matrix metalloproteinase-3,
      respectively. MiR-146a and miR-223 in polyarthritis showed correlations with
      matrix metalloproteinase-3. Expressions of miRNAs were altered in patients with
      JIA. Serum levels of miR-223 may be a potential disease biomarker. Investigation
      of miRNAs could be helpful in understanding the pathogenesis of JIA and could aid
      in the identification of additional disease biomarkers. 

PMID- 25846831
TI  - Macrophage activation syndrome in the course of monogenic autoinflammatory
      disorders.
AB  - An overwhelming activation of cytotoxic T cells and well-differentiated
      macrophages leading to systemic overload of inflammatory mediators characterizes
      the so-called macrophage activation syndrome (MAS); this potentially life
      threatening clinical entity may derive from several genetic defects involved in
      granule-mediated cytotoxicity but has been largely observed in patients with
      juvenile idiopathic arthritis, many rheumatologic diseases, infections, and
      malignancies. The occurrence of MAS in the natural history or as the revealing
      clue of monogenic autoinflammatory disorders (AIDs), rare conditions caused by
      disrupted innate immunity pathways with overblown release of proinflammatory
      cytokines, has been only reported in few isolated patients with cryopyrin
      associated periodic syndrome, mevalonate kinase deficiency, familial
      Mediterranean fever, and tumor necrosis factor receptor-associated periodic
      syndrome since 2001. All these patients displayed various clinical, laboratory,
      and histopathologic features of MAS and have often required intensive care
      support. Only one patient has died due to MAS. Defective cytotoxic cell function
      was documented in a minority of patients. Corticosteroids were the first-line
      treatment, but anakinra was clinically effective in three refractory cases. Even
      if MAS and AIDs share multiple clinical features as well as heterogeneous
      pathogenetic scenes and a potential response to anti-interleukin-1 targeted
      therapies, MAS requires a prompt specific recognition in the course of AIDs due
      to its profound severity and high mortality rate. 

PMID- 25846833
TI  - Diagnosis and treatment of clinically amyopathic dermatomyositis (CADM): a case
      series and literature review.
AB  - The objective of this study was to report the clinical course of a cohort of
      patients with clinically amyopathic dermatomyositis (CADM) in correlation to the
      presence or absence of anti-melanoma differentiation-associated gene 5 (MDA-5)
      antibody. Five patients with CADM presented to our rheumatology unit between
      September 1, 2011 and March 31, 2014. We hereby present their clinical course,
      laboratory findings, imaging modalities, functional tests, and treatments
      regimens. Our cohort included five patients, with a mean age of 41.8 +/- 17.7.
      Three patients, all anti-MDA-5 antibody positive, developed rapidly progressive
      interstitial lung disease (ILD) within 4.3 +/- 4.5 months of presentation. Two of
      these patients succumbed to their disease within 30 months of diagnosis despite
      intensive immunosuppressive therapy. The third anti-MDA-5-positive patient with
      ILD is still stable, 20 months from disease onset, on massive combination
      therapy. One patient developed CADM associated with the anti-p155/140 antibody, a
      year after completing chemotherapy for non-seminomatous germ cell tumor. He
      presented with a benign clinical course with no evidence of ILD and no recurrence
      of malignancy after 20 months of follow-up. The fifth patient in our cohort, who
      is anti-MDA-5 negative and has no evidence of malignancy, also enjoys a benign
      clinical course. The presence of anti-MDA-5 antibodies in CADM patients is
      associated with rapidly progressive ILD and a poor prognosis. The serologic
      profile of patients with CADM should be routinely evaluated and integrated with
      clinical data in the management of these patients. 

PMID- 25846832
TI  - Are temporomandibular joint signs and symptoms associated with magnetic resonance
      imaging findings in juvenile idiopathic arthritis patients? A longitudinal study.
AB  - The aims of this longitudinal study were to perform a comprehensive clinical
      evaluation of temporomandibular joint (TMJ) and to investigate the association
      between the clinical and magnetic resonance imaging (MRI) findings in the TMJs of
      patients with juvenile idiopathic arthritis (JIA). Seventy-five patients with JIA
      participated in this study. All patients underwent a rheumatological examination
      performed by a paediatric rheumatologist, a TMJ examination performed by a single
      dentist and an MRI with contrast of the TMJs. These examinations were scheduled
      on the same date. The patients were examined again 1 year later. Twenty-eight
      (37.3 %) patients reported symptoms at the first evaluation and 11 (14.7 %)
      patients at the second evaluation. In relation to signs, 35 (46.7 %) of the
      patients presented at least one sign at the first evaluation and 29 (38.7 %) at
      the second. Intense contrast enhancement of TMJ was significantly associated with
      disease activity (p < 0.001) at the first evaluation and a trend to significance
      was observed at the second (p = 0.056), with poly/systemic subtypes (p = 0.028
      and p = 0.049, respectively), with restricted mouth opening capacity (p = 0.013
      and p = 0.001, respectively), with the presence of erosions at both evaluations
      (p = 0.0001 and p < 0.0001, respectively) and with altered condylar shape at the
      second evaluation (p = 0.0005). TMJ involvement is highly prevalent in JIA
      patients, with asymptomatic children presenting severe structural alterations of
      the TMJ. The TMJ should always be evaluated in JIA patients, even in the absence
      of signs and symptoms.

PMID- 25846834
TI  - Health-related quality of life assessed by LupusQoL questionnaire and SF-36 in
      Turkish patients with systemic lupus erythematosus.
AB  - The LupusQoL is a disease-specific health-related quality of life (HRQoL) measure
      for patients with lupus. We conducted this study to compare the efficiency of
      LupusQoL-TR (validated Turkish version of the LupusQoL questionnaire) with the 36
      item Short-Form Health Survey (SF-36), a generic quality of life (QoL) scale, in
      Turkish patients with lupus. Both questionnaires were conducted at a single visit
      to the clinic. Disease activity was measured with the Systemic Lupus
      Erythematosus Disease Activity Index (SLEDAI). Associations between the LupusQoL
      TR and SF-36 domains were examined while also examining age, disease duration,
      and disease activity for each questionnaire. Descriptive statistics, Spearman's
      correlation coefficients, and Students t test were performed to analyze the data.
      A total of 113 consecutive patients with lupus (F/M 108:5, mean age 40.6 +/- 11.9
      years, mean disease duration 8.5 +/- 7.0 years) were included, and 69 % of these
      were active. The median SLEDAI score was 2 (0-24), the mean global LupusQoL-TR
      score was 60.9 +/- 23.3, and the mean SF-36 score was 41.2 +/- 9.0. There was a
      significant correlation between LupusQoL-TR and SF-36 mean scores (r = 0.83; p <
      0.001). QoL assessed by LupusQoL-TR and SF-36 did not correlate with disease
      activity (r = -0.11; p = 0.244 and r = -0.03; p = 0.721, respectively). LupusQoL
      TR and SF-36 questionnaires were beneficial instruments in evaluating HRQoL in
      Turkish lupus patients. However, LupusQoL-TR and SF-36 were not associated with
      SLEDAI scores, which suggested that QoL might be affected by other factors
      besides disease activity, especially in clinically inactive or mildly active
      patients.

PMID- 25846835
TI  - A synthetic workflow for coordinated direct observation and genetic tagging
      applied to a complex host-parasite interaction.
AB  - An important aspect influencing host specificity is a parasite's compatibility,
      or ability, to infect a potential host. Here, we examine the compatibility
      between different trematode genotypes of the same species and several host
      species. To execute this study, we developed a synthetic workflow which combines
      the use of a fluorescent dye and standard molecular techniques to study host
      parasite interactions and host specificity. The utility of the fluorescent dye,
      BIODIPY FL C12, was evaluated to label and track larval trematodes during
      experimental infections using the Cerithidea californica-trematode host-parasite
      system. Our results showed that low dye concentrations (200 nM) did not
      significantly affect survival or infectivity of Acanthoparyphium spinulosum and
      proved to be useful for labeling cercariae. Parasites were genotyped based on
      sequences from cytochrome oxidase subunit 1 (COI) and the nuclear internal
      transcribed spacer 1 (ITS1) prior to labeling and experimental infections.
      Samples with low COI PCR product yield were reamplified using the M13 tails to
      obtain enough material for sequencing. Three parasite genotypes were recovered
      and results from experimental infections demonstrated varying levels of host
      specificity. Of the three host species used (C. californica, Polydora nuchalis,
      Tagelus californianus), genotype B was unable to infect P. nuchalis. Genotype A
      individuals were less likely to infect P. nuchalis than the other host species.
      Additionally, genotype C was unable to infect any host offered in this study.
      These findings reflect possible suboptimal pairings between parasite genotype and
      host species. Furthermore, the present study provides procedures that are useful
      for exploring parasite ecology at the molecular level.

PMID- 25846836
TI  - A systematic review of sacral nerve stimulation for low anterior resection
      syndrome.
AB  - AIM: The efficacy of sacral nerve stimulation (SNS) in low anterior resection
      syndrome (LARS) is largely undocumented. A review of the literature was carried
      out to study this question. METHOD: Pubmed, Medline and Cochrane databases were
      searched for relevant articles up to August 2014. Studies were included if they
      evaluated the use of SNS following rectal resection and assessed at least one of
      the following end-points: bowel function, quality of life and ano-neorectal
      physiology. No restrictions on language or study size were made. RESULTS: Seven
      papers were identified including one case report and six prospective case series.
      These included 43 patients with a median follow-up of 15 months. After peripheral
      nerve evaluation definitive implantation was carried out in 34 (79.1%) patients.
      Overall, 32 (94.1%) of the 34 patients experienced improvement of symptoms which,
      based on intention to treat, was 32/43 (74.4%). CONCLUSION: The review suggests
      that SNS for faecal incontinence in LARS has success rates comparable to its use
      for other forms of faecal incontinence.

PMID- 25846837
TI  - Anorexia nervosa as a motivated behavior: Relevance of anxiety, stress, fear and
      learning.
AB  - The high comorbidity between anorexia nervosa (AN) and anxiety disorders is well
      recognized. AN is a motivated behavioral disorder in which habit formation is
      likely to contribute to the persistence of abnormal eating and exercise
      behaviors. Secondary alterations in brain circuitry underlying the reward value
      of food and exercise, along with disturbances in neuroendocrine hunger and
      satiety signaling arising from starvation and excessive exercise, are likely
      contributors to the maintenance of anorectic behaviors in genetically vulnerable
      individuals. The potential role of fear conditioning in facilitating onset of AN,
      or of impaired fear extinction in contributing to the high relapse rates observed
      following weight restoration, is of interest. Evidence from animal models of
      anxiety and human laboratory studies indicate that low estrogen impairs fear
      extinction. Low estradiol levels in AN may therefore play a role in perpetuating
      fear of food and fat in recently weight restored patients. Translational models
      including the activity based anorexia (ABA) rodent model of AN, and neuroimaging
      studies of fear extinction and conditioning, could help clarify the underlying
      molecular mechanisms and neurocircuitry involved in food avoidance behaviors in
      AN. Moreover, the adaptation of novel treatment interventions with efficacy in
      anxiety disorders may contribute to the development of new treatments for this
      impairing disorder. 

PMID- 25846838
TI  - Reproductive and sexual behaviour development of dam or artificially reared male
      lambs.
AB  - The objective of this study was to determine if artificially reared male lambs
      differ from those reared by their mothers in their reproductive development and
      sexual behaviour during the first breeding season and in their serum testosterone
      to a GnRH challenge at the end of the first breeding season. Lambs were assigned
      to two experimental groups: 1) artificially reared lambs, separated from their
      dams 24-36h after birth (Week 0) and fed sheep milk until 10weeks of age (group
      AR, n=14); and 2) lambs reared by their dams until 10weeks of age (group DR,
      n=13). Reproductive parameters and sexual behaviour were recorded from Weeks 9 to
      39. The GnRH challenge was performed on Week 40. Body weight, scrotal
      circumference, gonado-somatic index, testosterone concentration and sperm
      parameters were unaffected by group, but increased with age (P<0.0001). Lambs
      reared by their mothers had greater values of gonado-somatic index on Weeks 9, 16
      and 19 (P<0.05), and tended to reach puberty earlier than AR (22.9+/-0.7 vs.
      25.1+/-1.1weeks, respectively, P=0.087). Lambs reared by their mothers presented
      more lateral approaches and mount attempts than AR (P<0.05), and DR lambs
      presented more mounts on Weeks 32 and 39 than AR (P<0.05). Blood testosterone
      concentrations 3.5 and 4h after the GnRH challenge were higher in AR than in DR
      lambs (P<0.05). In conclusion mother rearing promoted sexual behaviour and
      reproductive performance of male lambs. 

PMID- 25846839
TI  - Acute exercise ameliorates craving and inhibitory deficits in methamphetamine: An
      ERP study.
AB  - This study aimed to determine the effect of acute exercise in the potential
      context of non-pharmacological intervention for methamphetamine (MA)-related
      craving; we additionally determine its effect on the inhibitory control induced
      by standard and MA-related tasks according to behavioral and neuroelectric
      measurements among MA-dependent individuals. The present study employed a within
      subjects, counterbalanced design. A total of 24 participants who met the DSM-IV
      criteria for MA dependence were recruited. The craving level, reaction time, and
      response accuracy, as well as the event-related potential (ERP) components N2 and
      P3, were measured following exercise and the control treatment in a
      counterbalanced order. The exercise session consisted of an acute stationary
      cycle exercise at a moderate intensity, whereas the control treatment consisted
      of an active reading session. The self-reported MA craving was significantly
      attenuated during, immediately following, and 50min after the exercise session
      compared with the pre-exercise ratings, whereas the craving scores at these time
      points following exercise were lower than those for the reading control session.
      Acute exercise also facilitated inhibitory performance in both the standard and
      MA-related Go/Nogo tasks. A larger N2 amplitude, but not a larger P3 amplitude,
      was observed during both tasks in the exercise session and the Nogo condition
      compared with the reading control session and the Go condition. This is the first
      empirical study to demonstrate these beneficial effects of acute aerobic exercise
      at a moderate intensity on MA-related craving and inhibitory control in MA
      dependent individuals. These results suggest a potential role for acute aerobic
      exercise in treating this specific type of substance abuse. 

PMID- 25846840
TI  - Evaluation of Toxocara cati Excretory-Secretory Larval Antigens in Serodiagnosis
      of Human Toxocariasis.
AB  - BACKGROUND: Toxocariasis is the clinical term that is applied to infection in the
      human host with Toxocara species larvae. Serological tests are important tools
      for the diagnosis of toxocariasis. The aim of this study was to evaluate the
      excretory-secretory (ES) antigens of T. cati larvae using enzyme-linked
      immunosorbent assay (ELISA) and also Western blotting for serodiagnosis of human
      toxocariasis. METHOD: The ES antigens were prepared from T. cati third-stage
      larvae. Serum samples were obtained from 33 confirmed cases of toxocariasis, 35
      patients infected with other parasitic diseases, and 30 from healthy individuals
      tested with ELISA and immunoblotting. RESULTS: The ELISA showed appropriate
      performance in term of specificity (96.7%) and sensitivity (97.0%).
      Electrophoretic analysis of T. cati ES antigens revealed a range of 20- to 150
      kDa fractions. The highest sensitivity was achieved with 42- and 50-kDa
      fractions. CONCLUSION: The ELISA analyses using T. cati ES antigens demonstrated
      good sensitivity and specificity compared to T. canis ES as antigens for
      diagnosis of human toxocariasis. Accordingly, application of Western blotting,
      based on 42- and 50-kDa fractions of ES antigens, can be recommended for the
      accurate diagnosis of toxocariasis.

PMID- 25846841
TI  - Maternal lifestyle during pregnancy and child psychomotor development - Polish
      Mother and Child Cohort study.
AB  - BACKGROUND: Nowadays special attention is paid to prenatal exposures to maternal
      lifestyle factors and their impact on a child development. AIM: The objective of
      this study was to evaluate the impact of modifiable maternal lifestyle factors on
      child neurodevelopment based on the Polish Mother and Child Cohort study.
      MATERIAL AND METHODS: The current analysis included 538 mother-child pairs. The
      following factors related to maternal lifestyle were considered: smoking and
      environmental tobacco smoke (ETS) exposure (based on the cotinine level in
      maternal saliva measured using LC-ESI+MS/MS method), alcohol consumption and
      leisure-time physical activity (LTPA) in pregnancy, pre-pregnancy BMI, and folic
      acid supplementations before and during pregnancy based on questionnaire data.
      Psychomotor development was assessed in children at the ages of one and two by
      the Bayley Scales of Infant and Toddler Development. RESULTS: Significant
      association was observed between prenatal exposure to tobacco constituents and a
      decreased child motor development in assessments performed at both ages (beta=
      0.8, p=0.01; beta=-1.4, p<0.001). Maternal pre-pregnancy underweight was
      associated with decreased language abilities at 12 months of age (beta=-5.2,
      p=0.01) and cognitive and motor development at 24 months of age, for which the
      associations were of borderline significance (p=0.06). The recommended level of
      LTPA during pregnancy was beneficial for child language development at two years
      of age (beta=4.8, p=0.02). For alcohol and folic acid consumption there were no
      significant associations with any of the analyzed domains of child
      neurodevelopment. CONCLUSIONS: Children prenatally exposed to tobacco compounds
      and those of underweight mothers had a decreased psychomotor development. The
      recommended level of LTPA during pregnancy had positive impact on child
      development. These results underscore the importance of policies and public
      health interventions promoting healthy lifestyle among women in reproductive age
      and during pregnancy.

PMID- 25846842
TI  - Digit ratio (2D:4D) and physical fitness (Eurofit test battery) in school
      children.
AB  - BACKGROUND: The relative lengths of the index finger to the ring finger (2D:4D)
      is sexually dimorphic and is thought to be a correlate of prenatal sex steroids
      (low 2D:4D=high prenatal testosterone and low prenatal oestrogen). In adults
      there have been reports that low 2D:4D is consistently associated with high
      sports performance. AIMS: To investigate correlations between 2D:4D and fitness
      levels in children. STUDY DESIGN: Right 2D:4D and body size were measured, in
      addition to flexibility, speed, endurance and strength (Eurofit tests). SUBJECTS:
      922 boys and 835 girls (mean ages (years): 10.8 +/- 1.01 and 10.07 +/- 1.00
      respectively). OUTCOME MEASURES: height, mass, BMI, triceps and subscapular
      skinfolds, 20 m shuttle run, sit and reach, standing broad jump, hand grip
      strength, 10 * 5m sprint, and the sit and reach test. RESULTS: Boys significantly
      outperformed the girls in the 10 * 5m sprints, the 20 m shuttle run, standing
      broad jump, and hand grip strength. In boys but not girls, 2D:4D was
      significantly negatively correlated with scores in all these tests except the
      standing broad jump. In girls but not boys, 2D:4D was significantly positively
      correlated to stature, mass, BMI and waist circumference. CONCLUSIONS: It is
      suggested that high prenatal testosterone and low prenatal oestrogen (low 2D:4D)
      is implicated in high sprinting speed, endurance and hand grip strength in boys.
      In girls low prenatal testosterone and high prenatal oestrogen is associated with
      large body size.

PMID- 25846843
TI  - Risk factors and consequences of conversion in laparoscopic major liver
      resection.
AB  - BACKGROUND: Although recent reports have suggested potential benefits of the
      laparoscopic approach in patients requiring major hepatectomy, it remains unclear
      whether conversion to open surgery could offset these advantages. This study
      aimed to determine the risk factors for and postoperative consequences of
      conversion in patients undergoing laparoscopic major hepatectomy (LMH). METHODS:
      Data for all patients undergoing LMH between 2000 and 2013 at two tertiary
      referral centres were reviewed retrospectively. Risk factors for conversion were
      determined using multivariable analysis. After propensity score matching, the
      outcomes of patients who underwent conversion were compared with those of matched
      patients undergoing laparoscopic hepatectomy who did not have conversion,
      operated on at the same centres, and also with matched patients operated on at
      another tertiary centre during the same period by an open laparotomy approach.
      RESULTS: Conversion was needed in 30 (13.5 per cent) of the 223 patients
      undergoing LMH. The most frequent reasons for conversion were bleeding and
      failure to progress, in 14 (47 per cent) and nine (30 per cent) patients
      respectively. On multivariable analysis, risk factors for conversion were patient
      age above 75 years (hazard ratio (HR) 7.72, 95 per cent c.i. 1.67 to 35.70; P =
      0.009), diabetes (HR 4.51, 1.16 to 17.57; P = 0.030), body mass index (BMI) above
      28 kg/m(2) (HR 6.41, 1.56 to 26.37; P = 0.010), tumour diameter greater than 10
      cm (HR 8.91, 1.57 to 50.79; P = 0.014) and biliary reconstruction (HR 13.99, 1.82
      to 238.13; P = 0.048). After propensity score matching, the complication rate in
      patients who had conversion was higher than in patients who did not (75 versus
      47.3 per cent respectively; P = 0.038), but was not significantly different from
      the rate in patients treated by planned laparotomy (79 versus 67.9 per cent
      respectively; P = 0.438). CONCLUSION: Conversion during LMH should be anticipated
      in patients with raised BMI, large lesions and biliary reconstruction. Conversion
      does not lead to increased morbidity compared with planned laparotomy.

PMID- 25846844
TI  - Glycation of Wild-Type Apomyoglobin Induces Formation of Highly Cytotoxic
      Oligomeric Species.
AB  - Protein glycation is a non-enzymatic, irreversible modification of protein amino
      groups by reactive carbonyl species leading to the formation of advanced
      glycation end products (AGEs). Several proteins implicated in neurodegenerative
      diseases have been found to be glycated in vivo and the extent of glycation is
      related to the pathologies of the patients. Although it is now accepted that
      there is a direct correlation between AGEs formation and the development of
      neurodegenerative diseases related to protein misfolding and amyloid aggregation,
      several questions still remain unanswered: whether glycation is the triggering
      event or just an additional factor acting on the aggregation pathway. We have
      recently shown that glycation of the amyloidogenic W7FW14F apomyoglobin mutant
      significantly accelerates the amyloid fibrils formation providing evidence that
      glycation actively participates to the process. In the present study, to test if
      glycation can be considered also a triggering factor in amyloidosis, we evaluated
      the ability of different glycation agents to induce amyloid aggregation in the
      soluble wild-type apomyoglobin. Our results show that glycation covalently
      modifies apomyoglobin and induces conformational changes that lead to the
      formation of oligomeric species that are not implicated in amyloid aggregation.
      Thus, AGEs formation does not trigger amyloid aggregation in the wild-type
      apomyoglobin but only induce the formation of soluble oligomeric species able to
      affect cell viability. The molecular bases of cell toxicity induced by AGEs
      formed upon glycation of wild-type apomyoglobin have been also investigated.

PMID- 25846846
TI  - Automated Analysis of Anterior Chamber Inflammation by Spectral-Domain Optical
      Coherence Tomography.
AB  - PURPOSE: This study was designed to determine the feasibility of anterior segment
      optical coherence tomography (AS-OCT) to objectively image and quantify the
      degree of AC inflammation. DESIGN: Prospective evaluation of a diagnostic test.
      PARTICIPANTS: Patients with anterior segment involving uveitis. METHODS:
      Observational case series of patients with uveitis. Single-line and 3-dimensional
      (3D) volume AS-OCT scans were manually graded to evaluate for the presence or
      absence of cells in the AC. Clinical grading scores were correlated to the number
      of cells seen in each line scan. An automated algorithm was developed to measure
      the number of cells seen in the 3D volume scan and compared with manual
      measurements and clinical grading scores. MAIN OUTCOME MEASURES: Degree of
      anterior segment inflammation. RESULTS: A total of 114 eyes from 76 patients were
      imaged, 83 eyes with line scans and 31 eyes with volume scans. The average number
      of cells on line scans was 0.13 for grade 0, 1.2 for grade 1/2+, 2.6 for grade
      1+, 5.7 for grade 2+, 15.5 for grade 3+, and 41.2 for grade 4+. Spearman
      correlation coefficient comparing clinical grade with the individual AS-OCT line
      scans was 0.967 (P < 0.0001). The range of cells in the automated cell count of
      3D volume scans was 13.60 to 1222; the range for manual cell counts was from 9.2
      to 2245. The Spearman correlation coefficients were r = 0.7765 (P < 0.0001) and r
      = 0.7484 (P < 0.0001) comparing the manual and automated cell counts with the
      clinical grade, respectively. Spearman correlation coefficient comparing the
      automatic cell counts with manual cell count in the 3D volume scan was 0.997 (P <
      0.0001). CONCLUSIONS: Anterior segment OCT can be used to image and grade the
      degree of AC inflammation. Clinical grading strongly correlates with the number
      of cells on AS-OCT line scans and volume scans. The automated algorithm to
      measure cell count had a high correlation to manual measurement of cells in the
      3D volume scans. This modality could be used to objectively grade response to
      treatment.

PMID- 25846845
TI  - Population pharmacokinetic analysis of tacrolimus in Mexican paediatric renal
      transplant patients: role of CYP3A5 genotype and formulation.
AB  - AIMS: The aims of this study were (i) to develop a population pharmacokinetic
      (PK) model of tacrolimus in a Mexican renal transplant paediatric population (n =
      53) and (ii) to test the influence of different covariates on its PK properties
      to facilitate dose individualization. METHODS: Population PK and variability
      parameters were estimated from whole blood drug concentration profiles obtained
      at steady-state using the non-linear mixed effect modelling software NONMEM(r)
      Version 7.2. RESULTS: Tacrolimus PK profiles exhibited high inter-patient
      variability (IPV). A two compartment model with first order input and elimination
      described the tacrolimus PK profiles in the studied population. The relationship
      between CYP3A5 genotype and tacrolimus CL/F was included in the final model. CL/F
      in CYP3A5*1/*1 and *1/*3 carriers was approximately 2- and 1.5-fold higher than
      in CYP3A5*3/*3 carriers (non-expressers), respectively, and explained almost the
      entire IPV in CL/F. Other covariates retained in the final model were the
      tacrolimus dose and formulation type. Limustin(r) showed markedly lower
      concentrations than the rest of the formulations. CONCLUSIONS: Population PK
      modelling of tacrolimus in paediatric renal transplant recipients identified the
      tacrolimus formulation type as a significant covariate affecting the blood
      concentrations and confirmed the previously reported significant effect of CYP3A5
      genotype on CL/F. It allowed the design of a proposed dosage based on the final
      model that is expected to help to improve tacrolimus dosing.

PMID- 25846848
TI  - Single prolonged stress induces dysfunction of endoplasmic reticulum in a rat
      model of post-traumatic stress disorder.
AB  - The aim of the present study, was to investigate the involvement of the
      endoplasmic reticulum (ER) in post-traumatic stress disorder (PTSD) by detecting
      changes of ER chaperone protein 78 and ER-resident caspase 12 in the basolateral
      amygdala after exposure to single prolonged stress (SPS). The established rat
      model of PTSD was generated by exposure of the animals to SPS. The expression of
      glucose-regulated protein 78 (GRP78) was examined by immunofluorescence, western
      blot and reverse transcription-polymerase chain reaction (RT-PCR), and the
      expression of caspase 12 was examined by western blot and RT-PCR. The
      morphological changes of the ER were detected by transmission electron
      microscopy. The results showed that GRP78 expression significantly increased when
      compared to that in the control group 1 day after SPS exposure (P<0.05). The
      expression of caspase 12 was also significantly upregulated after SPS exposure
      and peaked at 7 days following SPS (P<0.05). Morphological evaluation showed that
      a tumescent ER, ER vacuolization and degranulation of the ER were present
      following SPS. In conclusion, the findings of the present study suggested that
      SPS induced GRP78 and caspase 12 upregulation and morphological changes of the ER
      in the amygdala, which may play important roles in the pathogenesis of PTSD rats.

PMID- 25846847
TI  - Two-year outcomes of "treat and extend" intravitreal therapy for neovascular age
      related macular degeneration.
AB  - PURPOSE: To report 24-month outcomes of anti-vascular endothelial growth factor
      (VEGF) therapy for treatment-naive eyes with neovascular age-related macular
      degeneration (nAMD) using a treat and extend treatment regimen in routine
      clinical practice. DESIGN: Database observational study. PARTICIPANTS: We
      included treatment-naive eyes receiving predominantly ranibizumab for nAMD in
      routine clinical practice treated using a treat and extend regimen that were
      tracked in the Fight Retinal Blindness observational registry. METHODS: A cohort
      of eyes treated by practitioners using exclusively a treat and extend regimen was
      extracted from the Fight Retinal Blindness observational registry. MAIN OUTCOME
      MEASURES: Change in visual acuity (VA) over 2 years and number of injections and
      visits. RESULTS: Data from 1198 eyes from 1011 patients receiving anti-VEGF
      therapy using a treat and extend regimen for treatment-naive nAMD between January
      2007 and December 2012 and with 24-month follow-up were included in the analysis.
      Mean VA increased by +5.3 logarithm of the minimum angle of resolution letters
      from 56.5 letters (20/80+1) at initial visit to 61.8 (20/60+2) letters at 24
      months. Mean VA gains improved and number of injections increased with successive
      years from +2.7 letters for eyes commencing in 2007 after a mean of 9.7
      injections in 2 years, to +7.8 letters for eyes commencing in 2012 after a mean
      of 14.2 injections over 2 years. The proportion of eyes with VA >20/40 increased
      from 27% when starting treatment to 45% after 24 months; the proportion with
      vision of <20/200 remained unchanged (13% initial, 11% at 24 months). Of the
      included eyes, 90.5% avoided a vision loss of >=15 letters. There was an overall
      mean of 13.0 injections over the 24 months, 7.5 injections in the first year and
      5.5 in the second year, with a mean of 14.8 clinic visits. CONCLUSIONS: These
      data indicate that eyes managed in routine clinical practice with a treat and
      extend regimen can achieve good visual outcomes while decreasing the burden of
      treatments and clinic visits.

PMID- 25846849
TI  - Old foes, new understandings: nuclear entry of small non-enveloped DNA viruses.
AB  - The nuclear import of viral genomes is an important step of the infectious cycle
      for viruses that replicate in the nucleus of their host cells. Although most
      viruses use the cellular nuclear import machinery or some components of this
      machinery, others have developed sophisticated ways to reach the nucleus. Some of
      these have been known for some time; however, recent studies have changed our
      understanding of how some non-enveloped DNA viruses access the nucleus. For
      example, parvoviruses enter the nucleus through small disruptions of the nuclear
      membranes and nuclear lamina, and adenovirus tugs at the nuclear pore complex,
      using kinesin-1, to disassemble their capsids and deliver viral proteins and
      genomes into the nucleus. Here we review recent findings of the nuclear import
      strategies of three small non-enveloped DNA viruses, including adenovirus,
      parvovirus, and the polyomavirus simian virus 40. 

PMID- 25846850
TI  - Gastroschisis and young mothers: What makes them different from other mothers of
      the same age?
AB  - BACKGROUND: Although young maternal age has been identified as a risk factor for
      gastroschisis, its role remains undisclosed. To our knowledge, the differences
      between young mothers of infants with gastroschisis and young mothers of infants
      with other pregnancy outcomes have not been established. The aim of this work was
      to compare characteristics of young mothers whose newborn had gastroschisis with
      same aged mothers of malformed and nonmalformed control infants, diagnosed within
      the ECLAMC maternity hospital network. METHODS: Data base records of live and
      stillborn infants of one of three groups (with isolated gastroschisis, with 1 of
      5 other isolated birth defects, and nonmalformed), and whose mothers were younger
      than 20 years, were selected. Secular trends were obtained for all birth defects;
      frequencies and odds ratios (OR) of demographic and reproductive variables were
      compared among the 3 groups. Significantly associated variables were adjusted
      with a multivariate regression. RESULTS: The association was higher with
      gastroschisis 1) than with other birth defects for African ancestry, smoking,
      adequate prenatal control and diagnosis 2) than with nonmalformed controls for
      maternal illnesses and alcohol 3) and than both for previous pregnancy loss and
      medication, mainly sex hormones. After adjustment, only previous pregnancy loss
      maintained its significance when compared with malformed (OR = 2.34; 1.37-3.97; P
      = 0.002), as well as with nonmalformed (OR = 3.43; 2.07-5.66; P < 0.001)
      controls. CONCLUSION: A previous pregnancy loss was identified as the main risk
      factor for gastroschisis, while an increased use of sex hormones, perhaps related
      to the previous loss, could trigger a disruptive mechanism, due to their
      thrombophilic effect.

PMID- 25846854
TI  - Life expectancy in bipolar disorder.
AB  - OBJECTIVE: Life expectancy in patients with bipolar disorder has been reported to
      be decreased by 11 to 20 years. These calculations are based on data for
      individuals at the age of 15 years. However, this may be misleading for patients
      with bipolar disorder in general as most patients have a later onset of illness.
      The aim of the present study was to calculate the remaining life expectancy for
      patients of different ages with a diagnosis of bipolar disorder. METHODS: Using
      nationwide registers of all inpatient and outpatient contacts to all psychiatric
      hospitals in Denmark from 1970 to 2012 we calculated remaining life expectancies
      for values of age 15, 25, 35 ? 75 years among all individuals alive in year 2000.
      RESULTS: For the typical male or female patient aged 25 to 45 years, the
      remaining life expectancy was decreased by 12.0-8.7 years and 10.6-8.3 years,
      respectively. The ratio between remaining life expectancy in bipolar disorder and
      that of the general population decreased with age, indicating that patients with
      bipolar disorder start losing life-years during early and mid-adulthood.
      CONCLUSIONS: Life expectancy in bipolar disorder is decreased substantially, but
      less so than previously reported. Patients start losing life-years during early
      and mid-adulthood.

PMID- 25846856
TI  - Spatio-temporal variability in the cannibalistic behaviour of European hake
      Merluccius merluccius: the influence of recruit abundance and prey availability.
AB  - Cannibalistic behaviour of European hake Merluccius merluccius was studied
      through the analysis of 49 836 gut contents belonging to individuals from 6 to 82
      cm in total length (L(T)). Samples were collected every autumn between 1993 and
      2009. The results showed that the consumption of conspecific individuals was
      consistent over space and time. The abundance, spatial distribution patterns and
      L(T) structure of M. merluccius recruits were the main variables involved in M.
      merluccius cannibalism. A geographical pattern was found since increasing
      cannibalism was observed in areas of recruit aggregations. The L(T) spectrum of
      recruits in autumn was also a key factor and dependent on the spawning period.
      When adults spawned from late spring to summer, an increasing cannibalism trend
      was found in autumn, due to the ideal size structure of the prey (M. merluccius
      recruits) for predators. Depth was also a significant variable, and a cannibal
      peak was detected at depths ranging between 50 and 200 m, coinciding with a
      spatial overlap of predator (pre-adults) and prey (recruits). The cannibalistic
      behaviour of M. merluccius began at c. 12 cm, although 75% were mid-sized
      individuals between 16 and 30 cm. Additionally, 90% of prey-hake were recruits
      <18.5 cm. Some biological and ecological aspects such as growth rate, spawning
      period, predation and competition interactions and the effect of some
      oceanographic events on M. merluccius cannibalism are also discussed.

PMID- 25846855
TI  - Do experimental units of different scale affect the biological performance of
      European sea bass Dicentrarchus labrax larvae?
AB  - The effects of different tank volumes (2000, 500 and 40 l) on European sea bass
      Dicentrarchus labrax larval rearing, relating to growth, survival, quality and
      stress variables, were investigated. A dynamic energy budget (DEB) model was used
      to analyse the results. The hydrodynamics of the tanks exhibited differences,
      with the water currents in the 2000 l tanks to be almost one order of magnitude
      stronger than those in the 40 l ones. Important differences in fish growth were
      observed between small and large tank-rearing volumes, with the smallest tank
      resulting in the slowest growth. Based on the DEB model analysis, growth
      differences were related to feeding rates, with growth in the smaller tank
      limited by food availability. Differences in survival rates were not
      statistically significant among the tank-rearing volumes. The quality evaluation
      of the fry (in terms of swimbladder, jaw and skeletal abnormalities) showed
      differences, with the smallest tank having the highest percentage of deformed
      individuals. This could be attributed to both the feeding variances and the
      hydrodynamics in the tanks. No differences were observed in terms of whole-body
      cortisol at the two developmental stages; flexion, and when the larvae body was
      fully covered by melanophores; when analysis was performed. This indicates that
      the allostatic load exerted on fish of different groups was similar and inside
      the fish-coping abilities range, in terms of the cortisol response axis. The
      selection of the experimental scale is of importance, especially when the results
      are to be transferred and applied on an industrial scale. 

PMID- 25846857
TI  - Growth and mortality of larval Myctophum affine (Myctophidae, Teleostei).
AB  - The growth and mortality rates of Myctophum affine larvae were analysed based on
      samples collected during the austral summer and winter of 2002 from south-eastern
      Brazilian waters. The larvae ranged in size from 2.75 to 14.00 mm standard length
      (L(S)). Daily increment counts from 82 sagittal otoliths showed that the age of
      M. affine ranged from 2 to 28 days. Three models were applied to estimate the
      growth rate: linear regression, exponential model and Laird-Gompertz model. The
      exponential model best fitted the data, and L(0) values from exponential and
      Laird-Gompertz models were close to the smallest larva reported in the literature
      (c. 2.5 mm L(S)). The average growth rate (0.33 mm day(-1)) was intermediate
      among lanternfishes. The mortality rate (12%) during the larval period was below
      average compared with other marine fish species but similar to some epipelagic
      fishes that occur in the area.

PMID- 25846858
TI  - Comparison of the feeding apparatus and diet of European sardines Sardina
      pilchardus of Atlantic and Mediterranean waters: ecological implications.
AB  - In this study, the feeding apparatus (gill rakers, GR) and the diet composition
      of European sardine Sardina pilchardus populations living in two contrasting
      environments were compared: the upwelling area off western Iberia and the
      comparatively less productive region of the north-western Mediterranean Sea. The
      importance of local adaptations in the trophic ecology of this species was
      estimated. Sardina pilchardus from the Atlantic Iberian coast and from the north
      western Mediterranean Sea have clear differences in the feeding apparatus and
      diet compositions. Those from the Atlantic Iberian coast have significantly more
      GRs than S. pilchardus of the same size range in the Mediterranean Sea. While S.
      pilchardus from the Mediterranean Sea mostly depend on prey ranging between 750
      1500 and 3000-4000 um, corresponding mostly to cladocerans, decapods and
      copepods, those from the Atlantic depend on smaller prey (50-500 and 1000-1500
      um) that include phytoplankton and copepods, particularly during summer months,
      and S. pilchardus eggs during the winter. The marked difference between the
      trophic ecology of S. pilchardus in the two areas studied appears to have
      originated from different dietary strategies that the two populations have
      adopted in contrasting feeding environments. These differences are shown to
      profoundly affect the size and quality of prey consumed, and the effect of
      cannibalism on the populations. 

PMID- 25846859
TI  - Homogeneity of parasite assemblages of Dules auriga (Serranidae) in
      hydrographically heterogeneous sites.
AB  - Parasite assemblages of Dules auriga are described for the first time from
      samples caught during research cruises in two localities of the Argentine
      Uruguayan Common Fishing Zone (AUCFZ) and are compared with four additional
      samples collected by commercial catches from the same region. A total of 178 fish
      were examined and 13 parasite species were found. This showed low species
      richness, a condition observed in some other small benthic species at a low
      trophic level. The composition of the parasite fauna was similar to those found
      on other host species in the region, sharing the same set of dominant species
      with other sympatric fishes, which have been identified as both typical and as
      indicators of this ecoregion: Grillotia carvajalregorum, Corynosoma australe and
      Hysterothylacium sp. Multivariate similarity analyses at the infracommunity and
      the component community levels indicated that the two samples caught at different
      latitudes in the AUCFZ display almost identical parasite assemblages. This
      repeatability in assemblage structure was also observed across samples from
      commercial catches. The homogeneity of the parasite assemblages is considered to
      be an intrinsic property of fish inhabiting the AUCFZ, independent of their
      ecology and trophic level. 

PMID- 25846860
TI  - Otolith shape: a population marker for Atlantic herring Clupea harengus.
AB  - Otolith shape variation of seven Atlantic herring Clupea harengus populations
      from Canada, the Faroe Islands, Iceland, Ireland, Norway and Scotland, U.K.,
      covering a large area of the species' distribution, was studied in order to see
      if otolith shape can be used to discriminate between populations. The otolith
      shape was obtained using quantitative shape analysis, transformed with Wavelet
      and analysed with multivariate methods. Significant differences were detected
      among the seven populations, which could be traced to three morphological
      structures in the otoliths. The differentiation in otolith shape between
      populations was not only correlated with their spawning time, indicating a strong
      environmental effect, but could also be due to differing life-history strategies.
      A model based on the shape differences discriminates with 94% accuracy between
      Icelandic summer spawners and Norwegian spring spawners, which are known to mix
      at feeding grounds. This study shows that otolith shape could become an accurate
      marker for C. harengus population discrimination. 

PMID- 25846861
TI  - Diet and cannibalism in plainfin midshipman Porichthys notatus.
AB  - The macroscopic and microscopic diversity of potential food items available in
      the nests of plainfin midshipman Porichthys notatus were quantified and compared
      with items that were found in the stomach and intestine (digestive tract) of the
      guarding males. In this species, males occur as one of two possible reproductive
      morphs: guarder males that care for young and sneaker males that parasitize the
      courtship and care of guarder males. Although it was predicted that guarder males
      would have fewer feeding opportunities due to their confinement to the nest, they
      in fact had more food items in their digestive tracts than did sneaker males and
      females. Date in the breeding season (a proxy of care duration) and body
      condition were not correlated with the amount of food consumed by guarder males.
      The main type of food consumed was P. notatus embryos; 69% of all guarder males
      sampled had cannibalized offspring. By comparing the diet of both sexes and
      tactics, this study sheds light on some of the strategies designed to cope with
      the costs of providing parental care. 

PMID- 25846862
TI  - Spatio-temporal isotopic signatures (delta13 C and delta15 N) reveal that two
      sympatric West African mullet species do not feed on the same basal production
      sources.
AB  - Potential trophic competition between two sympatric mullet species, Mugil
      cephalus and Mugil curema, was explored in the hypersaline estuary of the Saloum
      Delta (Senegal) using delta(13) C and delta(15) N composition of muscle tissues.
      Between species, delta(15) N compositions were similar, suggesting a similar
      trophic level, while the difference in delta(13) C compositions indicated that
      these species did not feed from exactly the same basal production sources or at
      least not in the same proportions. This result provides the first evidence of
      isotopic niche segregation between two limno-benthophageous species belonging to
      the geographically widespread, and often locally abundant, Mugilidae family. 

PMID- 25846863
TI  - Protein modification and maintenance systems as biomarkers of ageing.
AB  - Changes in the abundance and post-translational modification of proteins and
      accumulation of some covalently modified proteins have been proposed to represent
      hallmarks of biological ageing. Within the frame of the Mark-Age project, the
      workpackage dedicated to "markers based on proteins and their modifications" has
      been firstly focused on enzymatic and non-enzymatic post-translational
      modifications of serum proteins by carbohydrates. The second focus of the
      workpackage has been directed towards protein maintenance systems that are
      involved either in protein quality control (ApoJ/Clusterin) or in the removal of
      oxidatively damaged proteins through degradation and repair (proteasome and
      methionine sulfoxide reductase systems). This review describes the most relevant
      features of these protein modifications and maintenance systems, their fate
      during ageing and/or their implication in ageing and longevity. 

PMID- 25846865
TI  - Female sex of older patients is an independent risk factor for red blood cell
      alloimmunization after transfusion.
AB  - BACKGROUND: More women than men are encountered with red blood cell (RBC)
      antibodies. It is not clear whether this difference is explained by more
      immunizing events in women or by a different acting immune system. To assess
      whether there is a difference in the posttransfusion RBC alloimmunization rate
      between women and men, a study on RBC alloimmunization during a 5-year period was
      conducted in patients with at least one antibody follow-up more than 14 days
      after transfusion. STUDY DESIGN AND METHODS: Data on transfusion and antibody
      follow-up characteristics in female and male transfusion recipients from the
      Leiden University Medical Center laboratory database were collected. Hazard
      ratios of alloimmunization, according to sex of the transfusion recipient, were
      estimated using Cox proportional hazards regression models taking possible
      confounders into account. RESULTS: From a total of 1699 women and 1969 men who
      were eligible, 4.2% of women and 3.4% of men (relative risk, 1.3; 95% confidence
      interval [CI], 0.9-1.8) developed posttransfusion antibodies. Adjustment for
      confounders resulted in a relative 80% higher risk in women older than 45 years
      of age. CONCLUSION: Elder women beyond childbearing age have a higher risk of
      posttransfusion antibody formation compared to men.

PMID- 25846864
TI  - Disturbed calcium signaling in spinocerebellar ataxias and Alzheimer's disease.
AB  - Neurodegenerative disorders, such as spinocerebellar ataxias (SCAs) and
      Alzheimer's disease (AD) represent a huge scientific and medical question, but
      the molecular mechanisms of these diseases are still not clear. There is
      increasing evidence that neuronal calcium signaling is abnormal in many
      neurodegenerative disorders. Abnormal neuronal calcium release from the
      endoplasmic reticulum may result in disturbances of cell homeostasis, synaptic
      dysfunction, and eventual cell death. Neuronal loss is observed in most cases of
      neurodegenerative diseases. Recent experimental evidence supporting the role of
      neuronal calcium signaling in the pathogenesis of SCAs and AD is discussed in
      this review. 

PMID- 25846866
TI  - Chronic toxicological effects of beta-diketone antibiotics on Zebrafish (Danio
      rerio) using transcriptome profiling of deep sequencing.
AB  - Transcriptome analysis is important for interpreting the functional elements of
      the genome and revealing the molecular constituents of cells and tissues. Herein,
      differentially transcribed genes were identified by deep sequencing after
      zebrafish (Danio rerio) were exposed to beta-diketone antibiotics (DKAs); 23,129
      and 23,550 mapped genes were detected in control and treatment groups, a total of
      3238 genes were differentially expressed between control and treatment groups. Of
      these genes, 328 genes (213 up- and 115 down-regulation) had significant
      differential expression (p < 0.05) and an expression ratio (control/treatment) of
      >2 or <0.5. Additionally, we performed Gene Ontology (GO) category and Kyoto
      Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, and found
      266 genes in the treatment group with annotation terms linked to the GO category.
      A total of 77 differentially expressed transcriptional genes were associated with
      132 predicted KEGG metabolic pathways. Serious liver tissue damage was reflected
      and consistent with the differences in genetic classification and function from
      the transcriptome analysis. These results enhance our understanding of zebrafish
      developmental processes under exposure to DKA stress. (c) 2015 Wiley Periodicals,
      Inc. Environ Toxicol 31: 1357-1371, 2016.

PMID- 25846867
TI  - Age-related T2 changes in hindlimb muscles of mdx mice.
AB  - INTRODUCTION: Magnetic resonance imaging (MRI) was used to monitor changes in the
      transverse relaxation time constant (T2) in lower hindlimb muscles of mdx mice at
      different ages. METHODS: Young (5 weeks), adult (44 weeks), and old mdx (96
      weeks), and age-matched control mice were studied. Young mdx mice were imaged
      longitudinally, whereas adult and old mdx mice were imaged at a single time
      point. RESULTS: Mean muscle T2 and percent of pixels with elevated T2 were
      significantly different between mdx and control mice at all ages. In young mdx
      mice, mean muscle T2 peaked at 7-8 weeks and declined at 9-11 weeks. In old mdx
      mice, mean muscle T2 was decreased compared with young and adult mice, which
      could be attributed to fibrosis. CONCLUSIONS: MRI captured longitudinal changes
      in skeletal muscle integrity of mdx mice. This information will be valuable for
      pre-clinical testing of potential therapeutic interventions for muscular
      dystrophy.

PMID- 25846868
TI  - Restoration of the anti-proliferative and anti-migratory effects of 1,25
      dihydroxyvitamin D by silibinin in vitamin D-resistant colon cancer cells.
AB  - Colorectal carcinoma (CRC) is the third most common cancer in developed
      countries. A large fraction of cases are linked to chronic intestinal
      inflammation, with concomitant increased TNF-alpha release and elevated
      Snail1/Snail2 levels. These transcription factors in turn suppress vitamin D
      receptor (VDR) expression, resulting in loss of responsiveness to the protective
      anti-proliferative and anti-migratory effects of 1,25-dihydroxyvitamin D (1,25D).
      Experimental and epidemiologic evidence support the use of natural products to
      target CRC. Here we show that the flavonolignan silibinin reverses the TNF-alpha
      induced upregulation of Snail1 and Snail2 in the 1,25D-resistant human colon
      carcinoma cells HT-29. These silibinin effects are accompanied by an increase in
      VDR levels; Snail1 overexpression reverses these silibinin effects. Silibinin
      also restores promoter activity from a vitamin D-response element (VDRE) reporter
      construct. While 1,25D had no significant effect on HT-29 and SW480-R cell
      proliferation and migration, co-treatment with silibinin restored 1,25D
      responsiveness. In addition, co-treatment with silibinin plus 1,25D decreased
      proliferation and migration at doses where silibinin alone had no effect. These
      findings demonstrate that this combination may present a novel approach to target
      CRC in conditions of chronic colonic inflammation. 

PMID- 25846870
TI  - Serum free beta-human chorionic gonadotropin in the three trimesters of
      pregnancy: effects of maternal characteristics and medical history.
AB  - OBJECTIVE: To define the contribution of maternal variables which influence the
      measured level of maternal serum free beta-human chorionic gonadotropin (beta
      hCG) in screening for pregnancy complications. METHODS: Maternal characteristics
      and medical history were recorded and serum free beta-hCG was measured in women
      with a singleton pregnancy attending for three routine hospital visits at 11 + 0
      to 13 + 6, 19 + 0 to 24 + 6 and 30 + 0 to 34 + 6 weeks' gestation. For
      pregnancies delivering phenotypically normal live births or stillbirths >= 24
      weeks' gestation, variables from maternal demographic characteristics and medical
      history that are important in the prediction of free beta-hCG were determined
      from a linear mixed-effects multiple regression. RESULTS: Serum free beta-hCG was
      measured in 94 985 cases in the first trimester, 7879 in the second trimester and
      8424 in the third trimester. Significant independent contributions to serum free
      beta-hCG were provided by gestational age, maternal weight, age and racial
      origin, cigarette smoking, method of conception, diabetes mellitus and family
      history of pre-eclampsia (PE) in the mother of the patient. The effects of some
      variables were similar and those for others differed in each trimester. Random
      effects multiple regression analysis was used to define the contribution of
      maternal variables that influence the measured level of serum free beta-hCG and
      express the values as multiples of the median (MoMs). The model was shown to
      provide an adequate fit of MoM values for all covariates both in pregnancies that
      developed PE and in those without this pregnancy complication. CONCLUSIONS: A
      model was fitted to express measured serum free beta-hCG across the three
      trimesters of pregnancy as MoMs after adjusting for variables from maternal
      characteristics and medical history that affect this measurement.

PMID- 25846871
TI  - Genetic variability of CYP2C19 in a Mexican population: contribution to the
      knowledge of the inheritance pattern of CYP2C19*17 to develop the ultrarapid
      metabolizer phenotype.
AB  - CYP2C19 is a polymorphic enzyme that metabolizes a wide variety of therapeutic
      drugs that has been associated with altered enzymatic activity and adverse drug
      reactions. Differences in allele frequencies of the CYP2C19 gene have been
      detected in populations worldwide. Thus, we analysed the alleles CYP2C19*2,
      CYP2C19*3, CYP2C19*4 and CYP2C19*5 related to the poor metabolizer (PM) phenotype
      in a Mexican population sample (n = 238), as well as CYP2C19*17, unique allele
      related to ultrarapid metabolizer phenotype (UMs). Genotypes were determined
      using SNaPshot and TaqManqPCR assays. In addition to the wild-type CYP2C19*1
      allele (77.1%), we only found CYP2C19*17 (14.3%) and CYP2C19*2 (8.6%). Comparison
      with previous population reports demonstrated that these two SNPs are
      homogeneously distributed in Latin America (P > 0.05). Based on comparison with a
      previous pharmacokinetic study that determined the frequency of CYP2C19
      phenotypes in the same population (western Mexican), we obtained the following
      findings: (i) based on the difference between the frequency of genotypes
      CYP2C19*2/*2 (presumably PM) versus the observed prevalence of PM phenotypes (0.4
      versus 6.3%; Chi(2) = 9.58, P = 0.00196), we inferred the plausible presence of
      novel CYP2C19 alleles related to the PM phenotype; (ii) the prevalence of UMs was
      in disagreement with the dominant inheritance pattern suggested for CYP2C19*17
      (23.1 versus 4%; P < 0.00001); (iii) the apparent recessive inheritance pattern
      of CYP2C19*17, based on the agreement between homozygous CYP2C19*17/*17
      (presumably UMs) and the observed prevalence of UMs (2.1 versus 4%; (Chi(2) =
      1.048; P = 0.306). 

PMID- 25846869
TI  - Patient-reported goal achievement following onabotulinumtoxinA treatment in
      patients with neurogenic detrusor overactivity.
AB  - AIMS: To identify the self-reported treatment goals of patients with urinary
      incontinence (UI) due to neurogenic detrusor overactivity (NDO), determine
      whether patients achieved their goals following onabotulinumtoxinA treatment, and
      assess impact of neurogenic disease (multiple sclerosis or spinal cord injury)
      and/or clean intermittent catheterization (CIC) on goal achievement. METHODS:
      Data from two Phase III studies of onabotulinumtoxinA 200U (n = 227) or placebo
      (n = 241) in NDO patients (>=14 UI episodes/week; inadequately managed by
      anticholinergics) were pooled for analysis. At baseline, patients listed their
      top two qualitative treatment goals, which were distributed into eight
      subcategories. Six weeks post-treatment, patients rated whether they achieved
      their goals (5-point Likert scale). The frequency distribution of goals, the
      proportion of patients who achieved their goals, and goal achievement by etiology
      and use/non-use of CIC were assessed. RESULTS: At baseline, the most common goals
      were "be dry" (37.9%), "reduce other urinary symptoms" (26.4%), and "improve
      quality of life/sleep/emotions" (21.4%). Significantly higher proportions of
      onabotulinumtoxinA-treated patients achieved their overall goals versus placebo
      (62.0% vs. 17.2%; P <  0.001). OnabotulinumtoxinA treatment resulted in higher
      goal achievement in all goal categories, regardless of etiology. CIC use did not
      negatively impact patients' overall goal achievement; significantly higher
      proportions of onabotulinumtoxinA-treated patients versus placebo achieved their
      goals regardless of baseline catheterization use or de novo CIC during the first
      6 weeks of the study. CONCLUSIONS: The majority of patients with UI due to NDO
      achieved their self-determined treatment goals following onabotulinumtoxinA 200U
      therapy, regardless of etiology or CIC use. Neurourol. Urodynam. 35:595-600,
      2016. (c) 2015 The Authors. Neurourology and Urodynamics, published by Wiley
      Periodicals, Inc.

PMID- 25846872
TI  - Genetic analysis of fertility restoration under CGMS system in rice (Oryza sativa
      L.) using three-way test-cross method.
AB  - We studied the genetics of fertility restoration by producing three-way test
      cross (TWTC) hybrids involved different combinations of restorers, maintainers
      and partial restorers of rice. Pollen and spikelet fertility of 16 TWTC hybrids
      were studied. Six TWTC involving restorer/restorer combinations as male parents
      produced progenies with fertility levels ranging from complete to zero. No
      specific ratio of segregation was observed. The crosses involving
      maintainer/maintainer combinations as male parents showed fully fertile and
      partial fertile/sterile plants in their progenies. These could be due to
      nonallelic gene interactions for fertility restoration between the two restorer
      or maintainer parents, or due to the influence of some modifying genes in the
      nuclear genome. TWTC involving partial restorer / restorer and partial
      restorer/partial restorer as the male parents also produced fully fertile and
      partial fertile/sterile plants suggesting the complex genetics of fertility
      restoration in rice. There were no previous results depicting the complementation
      effects of maintainers for fertility restoration. 

PMID- 25846873
TI  - Distinct patterns of epigenetic marks and transcription factor binding sites
      across promoters of sense-intronic long noncoding RNAs.
AB  - Long noncoding RNAs (lncRNAs) are a new class of noncoding RNAs that have been
      extensively studied in the recent past as a regulator of gene expression,
      including modulation of epigenetic regulation. The lncRNAs class encompasses a
      number of subclasses, classified based on their genomic loci and relation to
      protein-coding genes. Functional differences between subclasses have been
      increasingly studied in the recent years, though the regulation of expression and
      biogenesis of lncRNAs have been poorly studied. The availability of genome-scale
      datasets of epigenetic marks has motivated us to understand the patterns and
      processes of epigenetic regulation of lncRNAs. Here we analysed the occurrence of
      expressive and repressive histone marks at the transcription start site (TSS) of
      lncRNAs and their subclasses, and compared these profiles with that of the
      protein-coding regions. We observe distinct differences in the density of histone
      marks across the TSS of a few lncRNA subclasses. The sense-intronic lncRNA
      subclass showed a paucity for mapped histone marks across the TSS which were
      significantly different than all the lncRNAs and protein-coding genes in most
      cases. Similar pattern was also observed for the density of transcription factor
      binding sites (TFBS). These observations were generally consistent across cell
      and tissue types. The differences in density across the promoter were
      significantly associated with the expression level of the genes, but the
      differences between the densities across long noncoding and protein-coding gene
      promoters were consistent irrespective of the expression levels. Apart from
      suggesting general differences in epigenetic regulatory marks across long
      noncoding RNA promoters, our analysis suggests a possible alternative mechanism
      of regulation and/or biogenesis of sense-intronic lncRNAs. 

PMID- 25846874
TI  - Simultaneous estimation of QTL effects and positions when using genotype data
      with errors.
AB  - Accurate genetic data are important prerequisite of performing genetic linkage
      test or association test. Currently, most analytical methods assume that the
      observed genotypes are correct. However, due to the constraint at the technical
      level, most of the genetic data that people used so far contain errors. In this
      paper, we considered the problem of QTL mapping based on biological data with
      genotyping errors. By analysing all possible genotypes of each individual in
      framework of multipleinterval mapping, we proposed an algorithm of inferring all
      model parameters through the expectation-maximization (EM) algorithm and
      discussed the hypothesis testing of the existence of QTL. We carried out
      extensive simulation studies to assess the proposed method. Simulation results
      showed that the new method outperforms the method that does not take the
      genotyping errors into account, and therefore it can decrease the impact of
      genotyping errors on QTL mapping. The proposed method was also applied to analyse
      a real barley dataset. 

PMID- 25846875
TI  - Distribution of genes associated with yield potential and water-saving in Chinese
      Zone II wheat detected by developed functional markers.
AB  - Functional markers (FMs) developed from sequence polymorphisms are present in
      allelic variants of a functional gene at a locus and are directly associated with
      phenotypic variations. In this study, FM linked to Rht-B1, Rht-D1, TaCwi-A1,
      TaSus2-2B, TaGW2-6A and Dreb-B1 genes conferring to yield potential and water
      saving were selected to analyse the distribution in 102 wheat varieties, most of
      which were authorized in the past decade and adapted to grow in Zone II of China.
      First, the semidwarfing genes Rht-B1b and Rht-D1b (mutant alleles) conferring to
      grain yield were analysed. The frequencies of favourable alleles Rht-B1b and Rht
      D1b were 32.4 and 58.8%, respectively. Comparing with the previous report, the
      frequency of Rht-B1b among cultivars in this study is similar to the frequency
      among cultivars released in the 1990s, while the frequency of Rht-D1b is slightly
      lower than the previous report 63.9%. Twelve (11.8%) cultivars neither contained
      Rht-B1b nor Rht-D1b, while only Yumai 66 contained both semidwarfing genes.
      Linyuan8 and Xinong 928 are heterozygous at RhtB1 locus and Zhengmai 9023 is
      heterozygous at both RhtB1 and Rht-D1 loci. Second, the TaCwi-A1, TaSus2-2B and
      TaGW2-6A genes considered as candidate genes related to grain weight were
      detected. We found that the frequencies of the favourable alleles were 76.5, 56.9
      and 69.6%, respectively. Among the 102 wheat varieties, 30 contained all the
      three favourable genes, 45 contained two of the three favourable genes and 27
      contained only one. There are eight wheat varieties (7.8%) in hybrid state at the
      TaCWI-A1 locus. Third, the designed FM linked to water-saving gene Dreb-B1 were
      validated on 102 wheat varieties. The results showed that the haplotypes of 47
      wheat varieties at the Dreb-B1 locus were same as that of Opata 85, and 55 wheat
      varieties showed the signal expected for W7984 (Opata 85 and W7984 are parents of
      the ITMI mapping population). This information will be useful for the wheat
      breeding programmes aiming at improving yield and water use efficiency in
      Shijiazhuang located in China Zone II. 

PMID- 25846876
TI  - Inbreeding in stochastic subdivided mating systems: the genetic consequences of
      host spatial structure, aggregated transmission dynamics and life history
      characteristics in parasite populations.
AB  - Inbreeding in parasite populations can have important epidemiological and
      evolutionary implications. However, theoretical models have predominantly
      focussed on the evolution of parasite populations under strong selection or in
      epidemic situations, and our understanding of neutral gene dynamics in parasite
      populations at equilibrium has been limited to verbal arguments or conceptual
      models. This study focusses on how host-parasite population dynamics affects
      observed levels of inbreeding in a random sample of parasites from an infinite
      population of hosts by bridging traditional genetic and parasitological processes
      utilizing a backward-forward branching Markov process embedded within a flexible
      statistical framework, the logarithmic-poisson mixture model. My results indicate
      that levels of inbreeding in parasites are impacted by demographic and/or
      transmission dynamics (subdivided mating, aggregated transmission dynamics and
      host spatial structure), and that this inbreeding is poorly estimated by
      'equilibrium' levels of inbreeding calculated assuming regular systems of mating.
      Specifically, the model reveals that at low levels of inbreeding (F <= 0.1),
      equilibrium levels of inbreeding are lower than those observed, while at high
      levels of inbreeding the opposite pattern occurs. The model also indicates that
      inbreeding could have important epidemiological implications (e.g., the spread of
      recessive drug resistance genes) by directly impacting the observed frequency of
      rare homozygotes in parasite populations. My results indicate that frequencies of
      rare homozygotes are affected by aggregated transmission dynamics and host
      spatial structure, and also that an increase in the frequency of rare homozygotes
      can be caused by a decrease in effective population size solely due to the
      presence of a subdivided breeding system.

PMID- 25846877
TI  - Identification of the trehalose-6-phosphate synthase gene family in winter wheat
      and expression analysis under conditions of freezing stress.
AB  - Trehalose plays an important role in metabolic regulation and abiotic stress
      tolerance in plants. Trehalose contents are potentially modulated by trehalose-6
      phosphate synthase (TPS), which is a key enzyme in the trehalose biosynthetic
      pathway. Using available wheat expressed sequence tag sequence information from
      NCBI and two wheat genome databases, we identified 12 wheat TPS genes and
      performed a comprehensive study on their structural, evolutionary and functional
      properties. The estimated divergence time of wheat TPS gene pairs and wheat-rice
      orthologues suggested that wheat and rice have a common ancestor. The number of
      TPS genes in the wheat genome was estimated to be at least 12, which is close to
      the number found in rice, Arabidopsis and soybean. Moreover, it has been reported
      earlier in other plants that TPS genes respond to abiotic stress, however, our
      study mainly analysed the TPS gene family under freezing conditions in winter
      wheat, and determined that most of the TPS gene expression in winter wheat was
      induced by freezing conditions, which further suggested that wheat TPS genes were
      involved in winter wheat freeze-resistance signal transduction pathways. Taken
      together, the current study represents the first comprehensive study of TPS genes
      in winter wheat and provides a foundation for future functional studies of this
      important gene family in Triticeae. 

PMID- 25846878
TI  - Characterization and fine mapping of a female fertility associated gene Ff1(t) in
      rice.
AB  - Female-sterile line can be used as a pollinator which has a great potential for
      hybrid seeds production. However, reports on female fertility are fewer than male
      fertility. Here, we characterized a recessive female fertility weakening mutant
      ff1(t) from rice. The spikelet fertility was seriously affected in the mutant.
      Reciprocal crosses and pollen vitality assay suggest that the decreased fertility
      was caused by the defective female gametophytes. Further investigation indicated
      that the mutant ovary development was inhibited before fertilization and failed
      swelling after flowering. Genetic analysis and fine mapping showed that the
      mutant was controlled by a single recessive gene, residing on a 16.8 kb region on
      the long arm of chromosome 1. The gene annotation indicated that there was only
      one putative gene encoding lysine decarboxylase-like protein in this region,
      which was allelic to LOG. Further, the sequence analysis was carried out and a
      substitution at the splice site of intron 2 / exon 3 was revealed in ff1(t)
      mutant, resulting in the change of reading frame. The finding of novel allele of
      LOG locus will facilitate the understanding of the mechanisms of female
      gametophyte development. 

PMID- 25846879
TI  - The effect of high glucose levels on the hypermethylation of protein phosphatase
      1 regulatory subunit 3C (PPP1R3C) gene in colorectal cancer.
AB  - DNA methylation is an epigenetic event that occurs frequently in colorectal
      cancer (CRC). Increased glucose level is a strong risk factor for CRC. Protein
      phosphatase 1 regulatory subunit 3C (PPP1R3C) modulates glycogen metabolism,
      particularly glycogen synthesis. The aim of this study was to investigate the
      effect of high glucose levels on DNA methylation of PPP1R3C in CRC. PPP1R3C was
      significantly hypermethylated in CRC tissues (76/105, 72.38%, P <0.05) and colon
      cancer cell lines (P < 0.05). CRC tissues obtained from patients with high
      glucose levels showed that the methylation of PPP1R3C was lower than in patients
      who had normal levels of glucose. When DLD-1 cells were cultured under conditions
      of high glucose, the methylation of PPP1R3C was repressed. The expression of
      PPP1R3C was inversely related to methylation status. In addition, a promoter
      luciferase assay showed that the transcriptional activity of PPP1R3C was
      increased in high glucose culture conditions. The number of cells decreased when
      PPP1R3C was silenced in DLD-1 cells. These results suggest that PPP1R3C, a novel
      hypermethylated gene in CRC, may play a critical role in cancer cell growth in
      association with glucose levels. 

PMID- 25846880
TI  - Genetic diversity, population structure and marker trait associations for seed
      quality traits in cotton (Gossypium hirsutum).
AB  - Cottonseed contains 16% seed oil and 23% seed protein by weight. High levels of
      palmitic acid provides a degree of stability to the oil, while the presence of
      bound gossypol in proteins considerably changes their properties, including their
      biological value. This study uses genetic principles to identify genomic regions
      associated with seed oil, protein and fibre content in upland cotton cultivars.
      Cotton association mapping panel representing the US germplasm were genotyped
      using amplified fragment length polymorphism markers, yielding 234 polymorphic
      DNA fragments. Phenotypic analysis showed high genetic variability for the seed
      traits, seed oil range from 6.47-25.16%, protein from 1.85-28.45% and fibre
      content from 15.88-37.12%. There were negative correlations between seed oil and
      protein content.With reference to genetic diversity, the average estimate of FST
      was 8.852 indicating a low level of genetic differentiation among subpopulations.
      The AMOVA test revealed that variation was 94% within and 6% among
      subpopulations. Bayesian population structure identified five subpopulations and
      was in agreement with their geographical distribution. Among the mixed models
      analysed, mixed linear model (MLM) identified 21 quantitative trait loci for lint
      percentage and seed quality traits, such as seed protein and oil. Establishing
      genetic diversity, population structure and marker trait associations for the
      seed quality traits could be valuable in understanding the genetic relationships
      and their utilization in breeding programmes. 

PMID- 25846882
TI  - Comparative analyses of genetic risk prediction methods reveal extreme diversity
      of genetic predisposition to nonalcoholic fatty liver disease (NAFLD) among
      ethnic populations of India.
AB  - Nonalcoholic fatty liver disease (NAFLD) is a distinct pathologic condition
      characterized by a disease spectrum ranging from simple steatosis to steato
      hepatitis, cirrhosis and hepatocellular carcinoma. Prevalence of NAFLD varies in
      different ethnic groups, ranging from 12% in Chinese to 45% in Hispanics. Among
      Indian populations, the diversity in prevalence is high, ranging from 9% in rural
      populations to 32% in urban populations, with geographic differences as well.
      Here, we wished to find out if this difference is reflected in their genetic
      makeup. To date, several candidate genes and a few genomewide association studies
      (GWAS) have been carried out, and many associations between single nucleotide
      polymorphisms (SNPs) and NAFLD have been observed. In this study, the risk allele
      frequencies (RAFs) of NAFLD-associated SNPs in 20 Indian ethnic populations (376
      individuals) were analysed. We used two different measures for calculating
      genetic risk scores and compared their performance. The correlation of additive
      risk scores of NAFLD for three Hapmap populations with their weighted mean
      prevalence was found to be high (R(2) = 0.93). Later we used this method to
      compare NAFLD risk among ethnic Indian populations. Based on our observation, the
      Indian caste populations have high risk scores compared to Caucasians, who are
      often used as surrogate and similar to Indian caste population in disease gene
      association studies, and is significantly higher than the Indian tribal
      populations. 

PMID- 25846881
TI  - De novo characterization of the alligator weed (Alternanthera philoxeroides)
      transcriptome illuminates gene expression under potassium deprivation.
AB  - As one of the three macronutrients, potassium participates in many physiological
      processes in plant life cycle. Recently, potassium-dependent transcriptome
      analysis has been reported in Arabidopsis, rice and soybean. Alligator weed is
      well known, particularly for its strong ability to accumulate potassium. However,
      the molecular mechanism that underlies potassium starvation responses has not yet
      been described. In this study, we used Illumina (Solexa) sequencing technology to
      analyse the root transcriptome information of alligator weed under low potassium
      stress. Further analysis suggested that 9253 differentially expressed genes
      (DEGs) were upregulated, and 2138 DEGs were downregulated after seven days of
      potassium deficiency. These factors included 121 transcription factors, 108
      kinases, 136 transporters and 178 genes that were related to stress. Twelve
      transcription factors were randomly selected for further analysis. The expression
      level of each transcription factor was confirmed by quantitative RT-PCR, and the
      results of this secondary analysis were consistent with the results of Solexa
      sequencing. Enrichment analysis indicated that 10,993 DEGs were assigned to 54
      gene ontology terms and 123 KEGG pathways. Approximately 24% of DEGs belong to
      the metabolic, ribosome and biosynthesis of secondary metabolite KEGG pathways.
      Our results provide a comprehensive analysis of the gene regulatory network of
      alligator weed under low potassium stress, and afford a valuable resource for
      genetic and genomic research on plant potassium deficiency. 

PMID- 25846883
TI  - A novel missense mutation in collagenous domain of EDA gene in a Chinese family
      with X-linked hypohidrotic ectodermal dysplasia.

PMID- 25846884
TI  - Methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism and alcohol
      consumption in hyperhomocysteinaemia: a population-based study from northeast
      India.

PMID- 25846885
TI  - Association of ACP1 gene polymorphisms and coronary artery disease in northeast
      Chinese population.

PMID- 25846886
TI  - Genetic evidence for susceptibility and resistance against scrapie in Indian
      sheep.

PMID- 25846887
TI  - Association of expression levels in skeletal muscle and a SNP in the MYBPC1 gene
      with growth-related trait in Japanese Black beef cattle.

PMID- 25846888
TI  - Increasing litter size in a sheep breed by marker-assisted selection of BMPR1B
      A746G mutation.

PMID- 25846889
TI  - Genomewide association study of body weight traits in Baluchi sheep.

PMID- 25846890
TI  - Importance of molecular diagnosis in the accurate diagnosis of systemic carnitine
      deficiency.

PMID- 25846891
TI  - Diverse expression of sucrose transporter gene family in Zea mays.

PMID- 25846892
TI  - A comparison of biological and cultural evolution.
AB  - This review begins with a definition of biological evolution and a description of
      its general principles. This is followed by a presentation of the biological
      basis of culture, specifically the concept of social selection. Further,
      conditions for cultural evolution are proposed, including a suggestion for
      language being the cultural replicator corresponding to the concept of the gene
      in biological evolution. Principles of cultural evolution are put forward and
      compared to the principles of biological evolution. Special emphasis is laid on
      the principle of selection in cultural evolution, including presentation of the
      concept of cultural fitness. The importance of language as a necessary condition
      for cultural evolution is stressed. Subsequently, prime differences between
      biological and cultural evolution are presented, followed by a discussion on
      interaction of our genome and our culture. The review aims at contributing to the
      present discussion concerning the modern development of the general theory of
      evolution, for example by giving a tentative formulation of the necessary and
      sufficient conditions for cultural evolution, and proposing that human creativity
      and mind reading or theory of mind are motors specific for it. The paper ends
      with the notion of the still ongoing coevolution of genes and culture.

PMID- 25846893
TI  - Induction of antigen-specific cytotoxic T lymphocytes by fusion cells generated
      from allogeneic plasmacytoid dendritic and tumor cells.

PMID- 25846894
TI  - (Pseudo)hemidystonia associated with anti-glutamic acid decarboxylase antibodies-
      a case report.

PMID- 25846895
TI  - A familial interstitial 4q35 deletion with no discernible clinical effects.
AB  - Small deletions on the long arm of distal chromosome 4 do not appear to result in
      gross congenital malformations, with the most frequently reported clinical
      findings including mild to moderate intellectual disability, learning
      disabilities and minor dysmorphic features. Here we report on a cytogenetically
      detectable familial interstitial chromosome 4 long arm deletion with no
      discernible phenotypic effects in a mother and her two daughters. The karyotypes
      of the mother and her two daughters were: 46,XX,del(4)(q35.1q35.2). Based on the
      results of FISH analyses using whole chromosome specific and subtelomeric probes,
      the karyotype was designated as: 46,XX,del(4)(q35.1q35.2). ish del(4)(q35
      qter)(WCP4+, 36P21+, dJ963K6-). Array-CGH analysis showed an interstitial
      deletion encompassing 5.75 Mb in the 4q35.1-q35.2 genomic region
      (chr4:184,717,878-190,469,337; hg19). This is the first report on a
      cytogenetically detectable familial interstitial chromosome 4 long arm deletion
      in which there are no discernible phenotypic effects. Both our findings and a
      review of the literature suggest that more detailed molecular analyses are needed
      in cases with distal chromosome 4 long arm deletions especially those with
      breakpoints in the 4q35 region to establish a more precise genotype-phenotype
      correlation.

PMID- 25846896
TI  - Halochromic and hydrochromic squaric acid functionalized perylene bisimide.
AB  - The functionalization of perylene bisimide by squaric acid afforded halochromic
      dyes with pronounced acidity. The dye senses solvent polarity, pH and humidity by
      means of pronounced changes in absorption spectra and thin film color through the
      intramolecular charge transfer between perylene and cyclobutene cores initiated
      by protonation/deprotonation. 

PMID- 25846897
TI  - Comprehensive 3-year study of the phenolic profile of Moroccan monovarietal
      virgin olive oils from the Meknes region.
AB  - The phenolic fraction of monovarietal virgin olive oils (VOOs) from the main
      Moroccan cultivar Picholine marocaine (142 samples from three different subareas
      of the Meknes region) was studied over three consecutive crop seasons (2011,
      2012, and 2013) using a powerful LC-MS methodology. First, LC-ESI-TOF MS was used
      to get a comprehensive characterization of the phenolic fraction; afterward, LC
      ESI-IT MS was utilized for further identification (MS/MS experiments) and
      quantitation purposes. A total of 28 phenolic compounds (and quinic acid) were
      determined, revealing the complex profile of Meknes VOO, composed, in order of
      abundance, by secoiridoids, phenolic alcohols, lignans, flavonoids, and phenolic
      acids. Tukey's test was applied to ascertain possible significant intraregional
      and/or interannual variations of the phenolic content of the Meknes VOOs under
      study. Results showed that the content of phenolic compounds was mainly related
      to the crop season. 

PMID- 25846898
TI  - An interlaboratory comparison program on ELF electric and magnetic fields
      measurements performed in Greece: Second round of the scheme.
AB  - The second round of an interlaboratory comparison program for extremely low
      frequency electric and magnetic fields measurements was performed at the High
      Voltage Laboratory of the National Technical University of Athens (Greece). The
      16 participating laboratories measured the following: (i) electric field produced
      by a scale transmission line; (ii) magnetic field produced by a medium voltage
      cable; and (iii) magnetic field and frequency at the center of a standard square
      coil and their delivered results were evaluated in all measurement scenarios with
      use of performance statistics z-scores. Deviations between z-scores based on
      usual estimators (mean value, standard deviation) and robust estimators (derived
      with the robust algorithm described by the International Organization for
      Standardization [ISO, 2005]) highlight improved performance of the robust
      algorithm. An overall comparison to measurement procedure and performance results
      of the first round proves effectiveness and necessity of the scheme. Improper
      instrumentation or calibration, instability of the field source and measurement
      position uncertainty are factors that may cause unsatisfactory performance of the
      participants.

PMID- 25846899
TI  - Progressive fat necrosis after breast augmentation with autologous lipotransfer:
      a cause of long-lasting high Fever and axillary lymph node enlargement.
AB  - Breast augmentation with autologous fat transfer has been widely practiced.
      However, this procedure is not exempt from complications even after technique
      refinement. This article aims to describe a case of long-lasting high fever,
      axillary node enlargement, and upper extremity dysfunction caused by liponecrosis
      after breast fat injection. Radiological and histological examination confirmed
      liponecrosis in bilateral breasts. Aspiration, drainage, and irrigation were
      performed along with empirical antibiotic treatment. The patient has made a full
      recovery from the operation. Liponecrosis, one of the complications after
      autologous fat grafting to the breast, may present widely different symptoms and
      signs. Even experienced surgeons should not underestimate it and caution should
      be used to maintain safety during and after the procedure. 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- 25846900
TI  - Hospitalisations from 1 to 6 years of age: effects of gestational age and severe
      neonatal morbidity.
AB  - BACKGROUND: To investigate whether the adverse infant health outcomes associated
      with early birth and severe neonatal morbidity (SNM) persist beyond the first
      year of life and impact on paediatric hospitalisations for children up to 6 years
      of age. METHODS: The study population included all singleton live births, >32
      weeks gestation in New South Wales, Australia, in 2001-2005, with follow-up to 6
      years of age. Birth data were probabilistically linked to hospitalisation data (n
      = 392 964). The odds of hospitalisation, mean hospital length of stay (LOS) and
      costs, and cumulative LOS were evaluated by gestational age and SNM using
      multivariable analyses. RESULTS: A total of 74 341 (18.9%) and 41 404 (10.5%)
      infants were hospitalised once and more than once, respectively. SNM was
      associated with increased odds of hospitalisation once (adjusted odds ratio [aOR]
      1.16 [95% confidence interval 1.10, 1.22]) and more than once [aOR 1.51 (1.43,
      1.61)]. Decreasing gestational age was associated with increasing odds of
      hospitalisation more than once from aOR 1.19 at 37-38 weeks to 1.49 at 33-34
      weeks. Average LOS and costs per hospital admission were increased with SNM but
      not with decreasing gestational age. Cumulative LOS was significantly increased
      with SNM and decreasing gestational age. CONCLUSIONS: Adverse effects of SNM and
      early birth persist between 1 and 6 years of age. Strategies to prevent early
      birth and reduce SNM, and to increase health monitoring of vulnerable infants
      throughout childhood may help reduce paediatric hospitalisations.

PMID- 25846901
TI  - Rocket launcher: A novel reduction technique for posterior hip dislocations and
      review of current literature.
AB  - OBJECTIVE: We provide a review of literature on reduction techniques for
      posterior hip dislocations and present our experience with a novel technique for
      the reduction of acute posterior hip dislocations in the ED, 'the rocket
      launcher' technique. METHODS: We present our results with six patients with
      prosthetic posterior hip dislocation treated in our rural ED. We recorded patient
      demographics. The technique involves placing the patient's knee over the
      shoulder, and holding the lower leg like a 'Rocket Launcher' allow the
      physician's shoulder to work as a fulcrum, in an ergonomically friendly manner
      for the reducer. We used Fisher's t-test for cohort analysis between reduction
      techniques. RESULTS: Of our patients, the mean age was 74 years (range 66 to 85
      years). We had a 83% success rate. The one patient who the 'rocket launcher'
      failed in, was a hemi-arthroplasty patient who also failed all other closed
      techniques and needed open reduction. When compared with Allis (62% success
      rate), Whistler (60% success rate) and Captain Morgan (92% success rate)
      techniques, there was no statistically significant difference in the
      successfulness of the reduction techniques. There were no neurovascular or
      periprosthetic complications. CONCLUSION: We have described a reduction technique
      for posterior hip dislocations. Placing the patient's knee over the shoulder, and
      holding the lower leg like a 'Rocket Launcher' allow the physician's shoulder to
      work as a fulcrum, thus mechanically and ergonomically superior to standard
      techniques.

PMID- 25846902
TI  - Membrane glucocorticoid receptors are localised in the extracellular matrix and
      signal through the MAPK pathway in mammalian skeletal muscle fibres.
AB  - KEY POINTS: Many studies have previously suggested the existence of stress
      hormone receptors on the cell membrane of many cell types, including skeletal
      muscle fibres; however, the exact localisation of these receptors and how they
      signal to the rest of the cell is poorly understood. In this study, we
      investigated the localisation and the mechanism(s) underlying the physiological
      functions of these receptors in mouse skeletal muscle cells. We found that the
      receptors were present throughout muscle development and that, in adult muscle
      fibres, they were localised in the extracellular matrix, satellite cells (muscle
      stem cells) and close to mitochondria. We also found that they signalled to the
      rest of the cell by activating enzymes called mitogen-activated protein kinases.
      From these results we suggest that, at physiological concentrations, stress
      hormones may be important in skeletal muscle differentiation, repair and
      regeneration. ABSTRACT: A number of studies have previously proposed the
      existence of glucocorticoid receptors on the plasma membrane of many cell types,
      including skeletal muscle fibres. However, their exact localisation and the
      cellular signalling pathway(s) they utilise to communicate with the rest of the
      cell are still poorly understood. In this study, we investigated the localisation
      and the mechanism(s) underlying the non-genomic physiological functions of these
      receptors in mouse skeletal muscle cells. The results show that the receptors
      were localised in the cytoplasm in myoblasts, in the nucleus in myotubes, in the
      extracellular matrix, in satellite cells and in the proximity of mitochondria in
      adult muscle fibres. Also, they bound laminin in a glucocorticoid-dependent
      manner. Treating small skeletal muscle fibre bundles with the synthetic
      glucocorticoid beclomethasone dipropionate increased the phosphorylation (=
      activation) of extracellular signal-regulated kinases 1 and 2, c-Jun N-terminal
      kinase and p38 mitogen-activated protein kinase. This occurred within 5 min and
      depended on the fibre type and the duration of the treatment. It was also
      abolished by the glucocorticoid receptor inhibitor, mifepristone, and a
      monoclonal antibody against the receptor. From these results we conclude that the
      non-genomic/non-canonical physiological functions of glucocorticoids, in adult
      skeletal muscle fibres, are mediated by a glucocorticoid receptor localised in
      the extracellular matrix, in satellite cells and close to mitochondria, and
      involve activation of the mitogen-activated protein kinase pathway.

PMID- 25846903
TI  - Clinical and procedural impact of aortic arch anatomic variants in carotid
      stenting procedures.
AB  - OBJECTIVES: To evaluate the impact of aortic arch variants in patients undergoing
      carotid artery stenting (CAS). BACKGROUND: CAS is increasingly carried out to
      treat the patients with internal carotid artery (ICA) stenosis. Aortic arch
      anatomy may influence its feasibility and affect clinical outcome. METHODS:
      Aortic arch digital subtraction angiography was systematically performed before
      CAS. Aortic arch elongation and bovine arch variants were recorded. Catheter
      manipulation time (CMT) was assessed for each patient. Adverse cardiovascular and
      cerebral events were assessed at 30 days. RESULTS: A total of 282 consecutive
      patients undergoing CAS under proximal balloon occlusion (57.8%) or distal filter
      (42.2%) neuroprotection were enrolled (age, 72 +/- 7 years; 72.7% males). Type II
      and III elongation variants were detected in 23.4% and 10.6% of patients,
      respectively; in total, 20.5% of the patients had bovine configuration. CMT was
      significantly influenced by aortic elongation (56.1 +/- 16.5 min in patients with
      type III aortic arch configuration compared to 38.2 +/- 11.6 min in patients with
      type I or type II, P < 0.01) and (in left ICA) by bovine configuration (49.2 +/-
      11.4 min in bovine variants vs. 37.7 +/- 11.5 min in patients with nonbovine
      anatomy, P < 0.001). CMT, but not aortic arch anatomy, resulted the only
      independent predictor of 30-day adverse outcome (hazard ratio [HR], 1.07; 95%
      confidence interval [CI], 1.03-1.10, P < 0.01). CONCLUSIONS: Adverse aortic arch
      anatomies are frequently encountered in CAS procedures and are associated to
      longer procedural times. A longer CMT increases the risk for adverse outcome.
      These data suggest that a careful procedure planning aimed at a reduction of CMT
      may be pivotal to improve the safety of CAS procedures.

PMID- 25846904
TI  - Medication use and predictors of sexual activity in men and women with CVD.
AB  - PURPOSE: To examine the influence of cardiac and noncardiac medications on sexual
      activity by drug classification and generation of the drug, among men and women
      with cardiovascular disease. DATA SOURCES: This study was a subanalysis (n = 224)
      of survey data from a cross-sectional sample of 336 cardiac patients. Self
      reported medications were categorized by generic drug name, classification, and
      subclass and/or generation of the drug. Sexual activity was the presence or
      absence of current sexual activity in the last 2 months. CONCLUSIONS: Patients
      taking generation one beta blockers, particularly men; diuretics as a class; and
      loop diuretics, were significantly less likely to be sexually active, with
      diuretics negatively influencing sexual activity in women, but not men. Certain
      antidepressant medications positively influenced sexual function, particularly
      for women. Nearly 20% of the variances in sexual activity were explained by
      younger age, fewer number of medications, higher education, and having a sexual
      partner. IMPLICATIONS FOR PRACTICE: A new finding meriting further study was that
      loop diuretics negatively impacted sexual activity, particularly for women; and
      further studies of women overall are clearly needed. Advance practice nurses play
      an important role in evaluating medications, proactively choosing drugs within a
      class or subclass less likely to cause sexual problems, and in promoting sexual
      quality of life of cardiac patients.

PMID- 25846905
TI  - Lowering the B1 threshold for improved BEAR B1 mapping.
AB  - PURPOSE: Accurate measurement of the nonuniform transmit radiofrequency field is
      necessary for magnetic resonance imaging applications. The radiofrequency field
      excitation amplitude (B1) is often obtained by acquiring a B1 map. We modify the
      B1 estimation using adiabatic refocusing (BEAR) method to extend its range to
      lower B1 magnitudes. THEORY AND METHODS: The BEAR method is a phase-based B1
      mapping method, wherein hyperbolic secant pulses induce a phase sensitivity to
      B1. The measurable B1 range is limited due to the adiabatic threshold of the
      pulses. We redesign the method to use flattened hyperbolic secant pulses, which
      have lower adiabatic thresholds. We optimize the flattened hyperbolic secant
      parameters to minimize phase sensitivity to frequency variations. RESULTS: We
      validate the performance of the new method via simulation and in vivo at 3T, and
      show that for n <= 8, accurate B1 maps can be acquired using reduced nominal peak
      B1 values. CONCLUSION: The adiabatic threshold for the BEAR method is reduced
      with flattened hyperbolic secant pulses, which are optimized for accurate phase
      to-B1 mapping over a frequency range, and allow for lower nominal B1 values. At
      3T, the nominal B1 is decreased by 52% and the sensitivity to B1 is increased by
      a factor of 3.8. This can improve the method's applicability for measurement of
      low B1.

PMID- 25846906
TI  - Olfactory function in Parkinson's Disease - effects of training.
AB  - BACKGROUND: Up to 90% of patients with Parkinson's disease (PD) exhibit olfactory
      dysfunction, but little is known about the effects of olfactory training. The
      study aim was to investigate whether the ability to identify olfactory stimuli
      can be improved by means of a brief training session. Furthermore, the impact of
      hyposmia on quality of life in PD was investigated by means of a questionnaire.
      METHODS: Olfactory function was rated in 34 patients with PD and in 26 controls
      before and after a training session. An additional 20 patients with PD served as
      a control group and were tested twice without an intervening training session.
      Long-term effects were evaluated in a small subset of patients. Cognitive tests
      and DaT SPECT scans were performed. RESULTS: We demonstrated significant same-day
      and long-term training effects in trained PD patients compared with non-trained
      PD patients. A slightly significant correlation was seen between the training
      effect and DaT putamen values, but not with cognitive test scores. Furthermore,
      patients with PD reported that hyposmia significantly decreased their quality of
      life. CONCLUSIONS: Patients with PD improved the number of correctly identified
      odors in an olfactory test through a brief training session. Olfactory training
      may have potential in rehabilitation of patients with PD.

PMID- 25846907
TI  - Visual and Vestibular Induced Eye Movements in Verbal Children and Adults with
      Autism.
AB  - This study assessed the functionality of vestibular, pursuit, and saccade
      circuitry in autism across a wide age range. Subjects were 79 individuals with
      autism (AUT) and 62 controls (CON) aged 5 to 52 years with IQ scores > 70. For
      vestibular testing, earth-vertical axis rotation was performed in darkness and in
      a lighted visual surround with a fixation target. Ocular motor testing included
      assessment of horizontal saccades and horizontal smooth pursuit. No between-group
      differences were found in vestibular reflexes or in mean saccade velocity or
      accuracy. Saccade latency was increased in the AUT group with significant age
      related effects in the 8-18 year old subgroups. There was a trend toward
      decreased pursuit gain without age effects. Normal vestibular-induced eye
      movements and normal saccade accuracy and velocity provide the most substantial
      evidence to date of the functional integrity of brainstem and cerebellar pathways
      in autism, suggesting that the histopathological abnormalities described in these
      structures may not be associated with intrinsic dysfunction but rather reflect
      developmental alterations related to forebrain cortical systems formation.
      Increased saccade latency with age effects adds to the extensive existing
      evidence of altered function and maturation of cortical systems in autism.

PMID- 25846908
TI  - The efficacy of amrubicin on central nervous system metastases originating from
      small-cell lung cancer: a case series of eight patients.
AB  - BACKGROUND: Central nervous system (CNS) metastases caused by small-cell lung
      cancer (SCLC) are incurable and therefore fatal. Although such metastases are
      usually treated with chemotherapy or radiotherapy, their sensitivity to these
      treatment measures is unclear. Amrubicin appears to be a promising agent for
      relapsed SCLC, but its effectiveness in CNS metastases originating from SCLC is
      unknown. METHODS: Between April 2002 and December 2009, 110 SCLC patients with
      CNS metastasis were treated at Shizuoka Cancer Center. Of these, we
      retrospectively reviewed 8 consecutive cases with CNS metastases originating from
      relapsed SCLC that were treated with amrubicin as a second-line therapy. RESULTS:
      We recorded three sensitive relapses and five refractory cases. Amrubicin yielded
      a CNS response rate of 50 % (2 partial responses and 2 complete response; 95 %
      CI, 21.5-78.5? %) and the disease control rate for CNS lesions was 87.5 % (95 %
      CI, 52.9-97.8 %). All of the sensitive relapse patients achieved a partial
      response. The median time to progression for CNS metastases was 150.5 days (95 %
      CI, 9-171 days), and the median survival time from the start of amrubicin
      administration was 230.5 days (95 % CI, 89-619 days). We also report a dramatic
      improvement in one patient's radiological result of intramedullary spinal cord
      metastasis and alleviation of her symptoms following amrubicin monotherapy
      including this case series. CONCLUSIONS: The results of this study suggest that
      amrubicin is active in patients with CNS metastases originating from SCLC.

PMID- 25846909
TI  - Microbiological quality of selected spices and herbs including the presence of
      Cronobacter spp.
AB  - The cultivation of spices and herbs in parts of the world characterized by warm
      climate and high humidity provides excellent conditions for the development of
      microorganisms, including the undesirable ones. The aim of this study was to
      determine the microbiological quality of spices and herbs available on the Polish
      market, considering the occurrence of Cronobacter species bacteria. Analyses
      covered 60 samples of commercial spices and herbs, including 38 samples of dried
      herbs (basil, bay leaves, thyme, oregano, tarragon, marjoram, dill, parsley,
      rosemary, lovage) and 16 samples of seasoning blends as well as 6 samples of
      spices seeds and fruits (pimento, black pepper, coriander). All samples were
      tested for the total count of aerobic mesophilic bacteria (TAMB) and for the
      presence of Cronobacter spp. In most of the samples of spices and herbs (60.0%),
      the TAMB did not exceed 10(4) CFU/g, and the level regarded as unacceptable
      (>10(6) CFU/g) was not identified in any of the samples. The presence of
      Cronobacter spp. was demonstrated in 10 (16.7%) samples of the analyzed products,
      however these were mainly samples of herbs (basil, tarragon, parsley) and one
      sample of a seasoning blend (Provence herbs). The highest microbiological
      contamination (TAMB) was found in samples of herbs (oregano, tarragon, basil) and
      in ready seasoning blends, in 21.1% and 25.0% of which the total count of aerobic
      mesophiles was in the range of 10(5)-10(6) CFU/g. In all samples of spices seeds
      and fruits (coriander, black pepper and pimento), the total count of aerobic
      bacteria reached <10(4) CFU/g. Results achieved in the study indicate good
      hygienic conditions in the production process of spices and herbs available on
      the Polish market. The study demonstrated also that dried spices and herbs may be
      carriers of Cronobacter species bacteria, though their presence in not often
      detected in products of this type.

PMID- 25846911
TI  - Modelling the influence of temperature, water activity and sodium metabisulphite
      on the growth and OTA production of Aspergillus carbonarius isolated from Greek
      wine grapes.
AB  - The purpose of the present study was to develop a modelling approach to quantify
      the effect of temperature (15-38  degrees C), a(w) (0.88-0.98) and sodium
      metabisulphite (NaMBS) concentration (0-200 mg L(-1)) on the growth and OTA
      production of Aspergillus carbonarius on a Grape Juice based Medium (GJM). Growth
      responses of the fungus were recorded over time in terms of colony diameter
      changes, and fitted to the primary model of Baranyi and the estimated maximum
      growth rates (MU(max)) and lag phases (lambda) were subsequently modelled as a
      function of temperature, a(w) and NaMBS concentration using the cardinal values
      model with inflection (CMI). Moreover, OTA production was measured during fungal
      growth and modelled as a function of the same parameters through a quadratic
      polynomial model. Results showed that NaMBS increased the lag phase of A.
      carbonarius, particularly at 38  degrees C/0.98 a(w) and 38  degrees C/0.96 a(w),
      as well as at lower a(w) levels regardless of temperature. In the lowest NaMBS
      concentration (50 mg L(-1)) there was no inhibitory effect, while at higher
      concentrations (100 and 150 mg L(-1)) fungal growth was delayed. No growth was
      observed at 200 mg L(-1) of NaMBS irrespective of temperature and a(w) levels.
      The optimum values for growth were found in the range 30-35  degrees C and 0.96
      a(w), while for OTA production at 20  degrees C and 0.98 a(w). The developed
      models were subjected to internal and external validation and presented
      satisfactory performance as inferred by graphical plots and statistical indices
      (bias and accuracy factors). The present study will complement the findings on
      the ecophysiology of A. carbonarius using NaMBS as an inhibitory agent.

PMID- 25846910
TI  - Activity of lysozyme on Lactobacillus hilgardii strains isolated from Port wine.
AB  - This work evaluated the effect of lysozyme on lactobacilli isolated from Port
      wine. Bacterial growth experiments were conducted in MRS/TJ medium and
      inactivation studies were performed in phosphate buffer (KH2PO4), distilled water
      and wine supplemented with different concentrations of lysozyme. The response of
      bacteria to lysozyme was found to be highly strain dependent. Some strains of
      Lactobacillus hilgardii together with Lactobacillus collinoides and Lactobacillus
      fructivorans were found to be resistant to concentrations of lysozyme as high as
      2000 mg/L. It was observed that among the L. hilgardii taxon the resistant
      strains possess an S-layer coat. Apparently, the strains of L. collinoides and L.
      fructivorans studied are also S-layer producers as suggested by the total protein
      profile obtained by SDS-PAGE. Thus, the hypothetical protective role of the S
      layer against the action of lysozyme was investigated. From the various
      treatments used to remove the protein from the surface of the cells, the one
      employing LiCl (5 M) was the most effective. LiCl pre-treated cells exposed to
      lysozyme (2000 mg/L) in KH2PO4 buffer maintained its resistance. However, when
      cells were suspended in distilled water an increased sensitivity to lysozyme was
      observed. Moreover, it was found that the addition of ethanol (20% v/v) to the
      suspension medium (distilled water) triggered a strong inactivation effect
      especially on cells previously treated with LiCl (reduction of >6 CFU log
      cycles). The results suggest that the S-layer exerts a protective effect against
      lysozyme and that the cell suspension medium influences the bacteriolysis
      efficiency. It was also noted that ethanol enhances the inactivation effect of
      lysozyme.

PMID- 25846912
TI  - The microbial diversity of an industrially produced lambic beer shares members of
      a traditionally produced one and reveals a core microbiota for lambic beer
      fermentation.
AB  - The microbiota involved in lambic beer fermentations in an industrial brewery in
      West-Flanders, Belgium, was determined through culture-dependent and culture
      independent techniques. More than 1300 bacterial and yeast isolates from 13
      samples collected during a one-year fermentation process were identified using
      matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      followed by sequence analysis of rRNA and various protein-encoding genes. The
      bacterial and yeast communities of the same samples were further analyzed using
      denaturing gradient gel electrophoresis of PCR-amplified V3 regions of the 16S
      rRNA genes and D1/D2 regions of the 26S rRNA genes, respectively. In contrast to
      traditional lambic beer fermentations, there was no Enterobacteriaceae phase and
      a larger variety of acetic acid bacteria were found in industrial lambic beer
      fermentations. Like in traditional lambic beer fermentations, Saccharomyces
      cerevisiae, Saccharomyces pastorianus, Dekkera bruxellensis and Pediococcus
      damnosus were the microorganisms responsible for the main fermentation and
      maturation phases. These microorganisms originated most probably from the wood of
      the casks and were considered as the core microbiota of lambic beer
      fermentations. 

PMID- 25846913
TI  - Management of Listeria monocytogenes in fermented sausages using the Food Safety
      Objective concept underpinned by stochastic modeling and meta-analysis.
AB  - In the present work, a demonstration is made on how the risk from the presence of
      Listeria monocytogenes in fermented sausages can be managed using the concept of
      Food Safety Objective (FSO) aided by stochastic modeling (Bayesian analysis and
      Monte Carlo simulation) and meta-analysis. For this purpose, the ICMSF equation
      was used, which combines the initial level (H0) of the hazard and its subsequent
      reduction (SigmaR) and/or increase (SigmaI) along the production chain. Each
      element of the equation was described by a distribution to investigate the effect
      not only of the level of the hazard, but also the effect of the accompanying
      variability. The distribution of each element was determined by Bayesian modeling
      (H0) and meta-analysis (SigmaR and SigmaI). The output was a normal distribution
      N(-5.36, 2.56) (log cfu/g) from which the percentage of the non-conforming
      products, i.e. the fraction above the FSO of 2 log cfu/g, was estimated at
      0.202%. Different control measures were examined such as lowering initial L.
      monocytogenes level and inclusion of an additional killing step along the process
      resulting in reduction of the non-conforming products from 0.195% to 0.003% based
      on the mean and/or square-root change of the normal distribution, and 0.001%,
      respectively.

PMID- 25846914
TI  - Microbial biofilms in seafood: a food-hygiene challenge.
AB  - Seafood forms a part of a healthy diet. However, seafood can be contaminated with
      foodborne pathogens, resulting in disease outbreaks. Because people consume large
      amounts of seafood, such disease outbreaks are increasing worldwide. Seafood
      contamination is largely due to the naturally occurring phenomenon of biofilm
      formation. The common seafood bacterial pathogens that form biofilms are Vibrio
      spp., Aeromonas hydrophila, Salmonella spp., and Listeria monocytogenes. As these
      organisms pose a global health threat, recent research has focused on elucidating
      methods to eliminate these biofilm-forming bacteria from seafood, thereby
      improving food hygiene. Therefore, we highlight recent advances in our
      understanding of the underlying molecular mechanisms of biofilm formation, the
      factors that regulate biofilm development and the role of quorum sensing and
      biofilm formation in the virulence of foodborne pathogens. Currently, several
      novel methods have been successfully developed for controlling biofilms present
      in seafood. In this review, we also discuss the epidemiology of seafood-related
      diseases and the novel methods that could be used for future control of biofilm
      formation in seafood. 

PMID- 25846915
TI  - Fermentation profile of green Spanish-style Manzanilla olives according to NaCl
      content in brine.
AB  - This work studies the effects of the partial substitution of NaCl with potassium
      and calcium chloride salts on the fermentation profile of Spanish-style green
      Manzanilla olives. For this purpose, response surface methodology based in an
      enlarged simplex centroid mixture design with constrain (?salts = 100 g/L) was
      used. Regarding to physicochemical characteristics, pH decreased when CaCl2
      increased, titratable acidity was lower in presence of KCl while combined acidity
      increased as the contents of KCl and CaCl2 were close to the barycentre of the
      experiment (~33.33% each salt). Regarding to microbiological profile,
      Enterobacteriaceae growth was slight stimulated in presence of high CaCl2
      contents, yeast patterns were not linked to the initial brine compositions, while
      the maximum lactic acid bacteria population decreased slightly as KCl and CaCl2
      increased in the proportion 1:1, although a moderate (equilibrated) content of
      both may be stimulating. Results obtained in this work show that Spanish-style
      green Manzanilla cv. can be fermented in diverse mixtures of chloride salts,
      albeit the initial CaCl2 should be limited to 20-30 g/L to prevent excessive
      Enterobacteriaceae growth; combining it with a similar proportion of KCl may also
      improve LAB predominance.

PMID- 25846916
TI  - Potential of Lactobacillus curvatus LFC1 to produce slits in Cheddar cheese.
AB  - Defects in Cheddar cheese resulting from undesired gas production are a sporadic
      problem that results in significant financial losses in the cheese industry. In
      this study, we evaluate the potential of a facultatively heterofermentative
      lactobacilli, Lactobacillus curvatus LFC1, to produce slits, a gas related defect
      in Cheddar cheese. The addition of Lb. curvatus LFC1 to cheese milk at log 3
      CFU/ml resulted in the development of small slits during the first month of
      ripening. Chemical analyses indicated that the LFC1 containing cheeses had less
      galactose and higher levels of lactate and acetate than the control cheeses. The
      composition the cheese microbiota was examined through a combination of two
      culture independent approaches, 16S rRNA marker gene sequencing and automated
      ribosomal intergenic spacer analysis; the results indicated that no known gas
      producers were present and that high levels of LFC1 was the only significant
      difference between the cheese microbiotas. A ripening cheese model system was
      utilized to examine the metabolism of LFC1 under conditions similar to those
      present in cheeses that exhibited the slit defect. The combined cheese and model
      system results indicate that when Lb. curvatus LFC1 was added to the cheese milk
      at log 3 CFU/ml it metabolized galactose to lactate, acetate, and CO2. For
      production of sufficient CO2 to result in the formation of slits there needs to
      be sufficient galactose and Lb. curvatus LFC1 present in the cheese matrix. To
      our knowledge, facultatively heterofermentative lactobacilli have not previously
      been demonstrated to result in gas-related cheese defects.

PMID- 25846917
TI  - Inactivation and potential reactivation of pathogenic Escherichia coli O157:H7 in
      bovine milk exposed to three monochromatic ultraviolet UVC lights.
AB  - The ultraviolet (UVC) light irradiation has been recently studied as a novel non
      thermal treatment method for milk. However, the potential reactivation of
      microorganisms following exposure to UVC light in milk medium was not studied
      yet. Therefore, the present study was conducted to determine the inactivation and
      reactivation of pathogenic Escherichia coli O157:H7 following exposure to UV
      light at three monochromatic wavelengths (222, 254 and 282 nm) in bovine milk.
      The results showed that inactivation of E. coli O157:H7 following exposure to the
      UV light at 254 nm was higher (P < 0.05) than that following exposure at 222 and
      282 nm at the same UV fluence of 5, 10 and 20 mJ/cm(2). The reactivation of E.
      coli O157:H7 was increased as the incubation time and temperature increased
      regardless of the UV light sources under dark incubation phases. The evaluated
      reactivation ratios of E. coli O157:H7 following exposure to the UV light at 254
      nm in milk were lower (P < 0.05) than that following exposure at 222 nm after 1
      to 6, 2 to 5 and 5-6 h incubation at 4, 20 and 37  degrees C, respectively.
      Furthermore, at most incubation time points, the reactivation ratio of E. coli
      O157:H7 following exposure to these three UV light sources were lower (P < 0.05)
      than that of non-UV treated cells regardless of the incubation temperature. The
      lowest reactivation ratios of E. coli O157:H7 were observed after milk exposure
      to the UV light at 254 nm at 4  degrees C incubation when compared to that
      following exposure to the UV light at 222 and 282 nm.

PMID- 25846918
TI  - Genomic diversity of Oenococcus oeni populations from Castilla La Mancha and La
      Rioja Tempranillo red wines.
AB  - The Oenococcus oeni populations of Tempranillo wines from Castilla La Mancha and
      La Rioja winemaking regions were analysed from one to three years and up to ten
      wineries. The objective was to evaluate the genetic variability and the O. oeni
      population structure. For this purpose a MLST scheme based on four loci (gyrB,
      purK, pgm and recP genes) and PFGE with SfiI restriction enzyme were developed
      for later combination. The results showed an O. oeni population completely
      adapted to winemaking regions. A purifying selection influenced the genes
      evolution, especially recP that along with purK were the most interesting loci to
      analyse the genetic variability of the isolates. In this way linkage
      disequilibrium and intergenic and intragenic recombination were determined
      between isolates. PFGE typing with UPGMA data were not coincident with the
      phylograms assessed for MLST by Maximum likelihood and combination of both
      techniques differentiated all the isolates as strains. Those results led the
      research to conclude that O. oeni population from CM and LR was a panmictic
      population with a slight clonal evolution, so subpopulations could not be
      described. A broader study including more winemaking regions with different grape
      varieties and distinct ways of elaborating would be interesting to complete the
      knowledge about O. oeni populations.

PMID- 25846919
TI  - Targeting Fusarium graminearum control via polyamine enzyme inhibitors and
      polyamine analogs.
AB  - Fusarium graminearum not only reduces yield and seed quality but also constitutes
      a risk to public or animal health owing to its ability to contaminate grains with
      mycotoxins. Resistance problems are emerging and control strategies based on new
      targets are needed. Polyamines have a key role in growth, development and
      differentiation. In this work, the possibility of using polyamine metabolism as a
      target to control F. graminearum has been assessed. It was found that putrescine
      induces mycotoxin production, correlating with an over expression of TRI5 and
      TRI6 genes. In addition, a homolog of the Saccharomyces cerevisiae TPO4 involved
      in putrescine excretion was up-regulated as putrescine concentration increased
      while DUR3 and SAM3 homologues, involved in putrescine uptake, were down
      regulated. When 2.5 mM D, l-alpha-difluoromethylornithine (DFMO) was added to the
      medium, DON production decreased from 3.2 to 0.06 ng/mm(2) of colony and growth
      was lowered by up to 70 per cent. However, exogenous putrescine could overcome
      DFMO effects. Five polyamine transport inhibitors were also tested against F.
      graminearum. AMXT-1505 was able to completely inhibit in vitro growth and DON
      production. Additionally, AMXT-1505 blocked F. graminearum growth in inoculated
      wheat spikes reducing DON mycotoxin contamination from 76.87 MUg/g to 0.62 MUg/g.

PMID- 25846921
TI  - Effect of ripeness stage during processing on Listeria monocytogenes growth on
      fresh-cut 'Conference' pears.
AB  - There are several factors that affect the shelf life of fresh-cut fruit,
      including the cultivar, the ripeness stage of the fruit during processing and the
      fruit's storage atmosphere and temperature. The effect of fruit ripeness during
      processing on the survival and growth of Listeria monocytogenes on fresh-cut
      'Conference' pear slices at different temperatures (5, 10 and 20  degrees C) was
      studied. The four ripeness stages studied in this work (assessed by a fruit's
      firmness) were mature-green (54-60 N), partially ripe (43-53 N), ripe (31-42 N)
      and overripe (<31 N). In our studies, pH, acidity and soluble solids content did
      not significantly change during conditioning at 20  degrees C. L. monocytogenes
      grew under all experimental conditions, showing an increase of approximately 2
      log CFU g(-1) after 8 days of storage at 5  degrees C. There were significant
      differences in the L. monocytogenes population between different ripeness stages
      at the end of the experiments at 10 and 20  degrees C. Regardless of the ripeness
      stage of a fresh-cut pear, the growth potential of L. monocytogenes increased
      with increasing temperature. A pear's ripeness stage during processing is an
      important consideration to ensure the quality of a fresh-cut pear, but it is not
      as important for preventing L. monocytogenes growth at common storage
      temperatures.

PMID- 25846920
TI  - Effect of sublethal preculturing on the survival of probiotics and metabolite
      formation in set-yoghurt.
AB  - The objective of this study was to investigate the effect of preculturing of
      Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp. lactis BB12 under
      sublethal stress conditions on their survival and metabolite formation in set
      yoghurt. Prior to co-cultivation with yoghurt starters in milk, the two probiotic
      strains were precultured under sublethal stress conditions (combinations of
      elevated NaCl and low pH) in a batch fermentor. The activity of sublethally
      precultured probiotics was evaluated during fermentation and refrigerated storage
      by monitoring bacterial population dynamics, milk acidification and changes in
      volatile and non-volatile metabolite profiles of set-yoghurt. The results
      demonstrated adaptive stress responses of the two probiotic strains resulting in
      their viability improvement without adverse influence on milk acidification. A
      complementary metabolomic approach using SPME-GC/MS and (1)H-NMR resulted in the
      identification of 35 volatiles and 43 non-volatile polar metabolites,
      respectively. Principal component analysis revealed substantial impact of the
      activity of sublethally precultured probiotics on metabolite formation
      demonstrated by distinctive volatile and non-volatile metabolite profiles of set
      yoghurt. Changes in relative abundance of various aroma compounds suggest that
      incorporation of stress-adapted probiotics considerably influences the
      organoleptic quality of product. This study provides new information on the
      application of stress-adapted probiotics in an actual food-carrier environment. 

PMID- 25846922
TI  - Bacteria and yeast microbiota in milk kefir grains from different Italian
      regions.
AB  - Kefir grains are a unique symbiotic association of different microrganisms,
      mainly lactic acid bacteria, yeasts and occasionally acetic acid bacteria,
      cohabiting in a natural polysaccharide and a protein matrix. The microbial
      composition of kefir grains can be considered as extremely variable since it is
      strongly influenced by the geographical origin of the grains and by the sub
      culturing method used. The aim of this study was to elucidate the bacteria and
      yeast species occurring in milk kefir grains collected in some Italian regions by
      combining the results of scanning electron microscopy analysis, viable counts on
      selective culture media, PCR-DGGE and pyrosequencing. The main bacterial species
      found was Lactobacillus kefiranofaciens while Dekkera anomala was the predominant
      yeast. The presence of sub-dominant species ascribed to Streptococcus
      thermophilus, Lactococcus lactis and Acetobacter genera was also highlighted. In
      addition, Lc. lactis, Enterococcus sp., Bacillus sp., Acetobacter fabarum,
      Acetobacter lovaniensis and Acetobacter orientalis were identified as part of the
      cultivable community. This work further confirms both the importance of combining
      culture-independent and culture-dependent approaches to study microbial diversity
      in food and how the combination of multiple 16S rRNA gene targets strengthens
      taxonomic identification using sequence-based identification approaches. 

PMID- 25846923
TI  - The combined efficacy of carvacrol and modified atmosphere packaging on the
      survival of Salmonella, Campylobacter jejuni and lactic acid bacteria on turkey
      breast cutlets.
AB  - The primary objective of this study was to determine the efficacy of carvacrol in
      combination with modified atmosphere packaging (MAP) in reducing Salmonella on
      turkey breast cutlets stored at 4  degrees C. In experiment I, carvacrol (0.5, 1,
      and 2% v/v) was applied as surface treatment and samples were stored under
      aerobic condition or as surface and dip treatments followed by storage in an
      environment of 100% carbon dioxide. The findings of the experiment I revealed the
      synergistic activity of carvacrol with carbon dioxide in reducing Salmonella when
      used as dip treatment compared to the surface treatment. In experiment II, turkey
      breast cutlets were dip treated with carvacrol (0.25, 0.5, and 1% v/v) for 30 s
      and stored under MAP (95% carbon dioxide and 5% oxygen) to evaluate the efficacy
      against Salmonella, Campylobacter jejuni and lactic acid bacteria on turkey
      breast cutlets. In experiment II, the combined application of carvacrol and MAP
      resulted in 1.0-2.0 log CFU/g reduction (P <= 0.05) of both Salmonella and
      Campylobacter on turkey breast cutlets for 7 d storage at 4  degrees C. MAP alone
      and in combination with carvacrol reduced lactic acid bacteria (P <= 0.05) on
      cutlets stored at 4  degrees C for 21 d period. There was no difference (P <=
      0.05) in meat color among treatments and controls except for an increased
      paleness of meat (P <= 0.05) observed for the 1% carvacrol treated cutlets stored
      under MAP after 21 d of storage. The high concentration of carbon dioxide and
      carvacrol treatments did not cause any alteration in meat pH (P <= 0.05). In
      conclusion, carvacrol was effective at a low concentration of 0.25% (v/v) in
      reducing Salmonella and C. jejuni by ~1.0 log CFU/g when stored under MAP.

PMID- 25846924
TI  - Effect of salinity and incubation time of planktonic cells on biofilm formation,
      motility, exoprotease production, and quorum sensing of Aeromonas hydrophila.
AB  - The aim of this study was to determine the effect of salinity and age of cultures
      on quorum sensing, exoprotease production, and biofilm formation by Aeromonas
      hydrophila on stainless steel (SS) and crab shell as substrates. Biofilm
      formation was assessed at various salinities, from fresh (0%) to saline water
      (3.0%). For young and old cultures, planktonic cells were grown at 30  degrees C
      for 24 h and 96 h, respectively. Biofilm formation was assessed on SS, glass, and
      crab shell; viable counts were determined in R2A agar for SS and glass, but
      Aeromonas-selective media was used for crab shell samples to eliminate bacterial
      contamination. Exoprotease activity was assessed using a FluoroTM protease assay
      kit. Quantification of acyl-homoserine lactone (AHL) was performed using the
      bioreporter strain Chromobacterium violaceum CV026 and the concentration was
      confirmed using high-performance liquid chromatography (HPLC). The concentration
      of autoinducer-2 (AI-2) was determined with Vibrio harveyi BB170. The biofilm
      structure at various salinities (0-3 %) was assessed using field emission
      electron microscopy (FESEM). Young cultures of A. hydrophila grown at 0-0.25%
      salinity showed gradual increasing of biofilm formation on SS, glass and crab
      shell; swarming and swimming motility; exoproteases production, AHL and AI-2
      quorum sensing; while all these phenotypic characters reduced from 0.5 to 3.0%
      salinity. The FESEM images also showed that from 0 to 0.25% salinity stimulated
      formation of three-dimensional biofilm structures that also broke through the
      surface by utilizing the chitin surfaces of crab, while 3% salinity stimulated
      attachment only for young cultures. However, in marked contrast, salinity (0.1
      3%) had no effect on the stimulation of biofilm formation or on phenotypic
      characters for old cultures. However, all concentrations reduced biofilm
      formation, motility, protease production and quorum sensing for old culture.
      Overall, 0-0.25% salinity enhanced biofilm formation and expression of quorum
      sensing regulatory genes in young cultures, whereas these responses were reduced
      when salinity was >0.25%. In old cultures, salinity at any concentrations (0.1
      3%) induced stress in A. hydrophila. The present study provides insight into the
      ecology of A. hydrophila growing on fish and crustaceans such as shrimp and crabs
      in estuarine and seawater.

PMID- 25846925
TI  - A novel microfluidic mixer-based approach for determining inactivation kinetics
      of Escherichia coli O157:H7 in chlorine solutions.
AB  - Determination of the minimum free chlorine concentration needed to prevent
      pathogen survival/cross-contamination during produce washing is essential for the
      development of science-based food safety regulations and practices. Although the
      trend of chlorine concentration-contact time on pathogen inactivation is
      generally understood, specific information on chlorine and the kinetics of
      pathogen inactivation at less than 1.00 s is urgently needed by the produce
      processing industry. However, conventional approaches to obtain this critical
      data have been unable to adequately measure very rapid responses. This paper
      reports our development, fabrication, and test of a novel microfluidic device,
      and its application to obtain the necessary data on pathogen inactivation by free
      chlorine in produce wash solution in times as short as 0.10 s. A novel
      microfluidic mixer with the capability to accurately determine the reaction time
      and control the chlorine concentration was designed with three inlets for
      bacterial, chlorine and dechlorinating solutions, and one outlet for effluent
      collection. The master mold was fabricated on a silicon wafer with microchannels
      via photopolymerization. Polydimethylsiloxane replicas with patterned
      microchannels were prototyped via soft lithography. The replicas were further
      assembled into the micromixer on glass via O2 plasma treatment, and the inlets
      were connected to a syringe pump for solution delivery. To determine the kinetics
      of free chlorine on pathogen inactivation, chlorine solutions of varying
      concentrations were first pumped into the micromixer, together with the addition
      of bacterial suspension of Escherichia coli O157:H7 through a separate inlet.
      This was followed by injection of dechlorinating solution to stop the chlorine
      pathogen reaction. The effluent was collected and the surviving bacteria cells
      were enumerated using a modified 'Most Probable Number' method. Free chlorine
      concentration was determined using a standard colorimetric method. The contact
      time was experimentally set by adjusting the solution flow rate, and was
      estimated by computational fluid dynamics modeling. Results showed that 1)
      pathogen inactivation was significantly affected by free chlorine concentration
      (P < 0.0001) and subsecond reaction time (P < 0.0001) and their interactions (P <
      0.0001); and 2) the current industry practice of using 1.0 mg/L free chlorine
      will require more than 1.00 s total contact to achieve a 5-log10 reduction in an
      E. coli O157:H7 population, whereas a 10.0 mg/L free chlorine solution will
      achieve 5-log10 reduction in as little as 0.25 s. Information obtained from this
      study will provide critical insight on kinetics of bacterial inactivation for a
      broad range of sanitizers and produce wash operational conditions, thus
      facilitating the development and implementation of science-based food safety
      regulations and practices for improving food safety.

PMID- 25846926
TI  - A five-year study on prevalence and antimicrobial resistance of Campylobacter
      from poultry carcasses in Poland.
AB  - During 2009-2013 a total of 2114 swab samples collected from broiler carcasses in
      all 16 voivodeships (administrative districts) of Poland were examined for the
      presence of Campylobacter jejuni and Campylobacter coli. The antimicrobial
      resistance of the isolates to ciprofloxacin, tetracycline and erythromycin using
      the MIC method was also tested. It was found that 1151 (54.4%) carcasses were
      contaminated with Campylobacter, with 50% of C. jejuni and C. coli species
      isolated from positive samples. The temporal trend in the prevalence of
      Campylobacter-positive samples demonstrated that the highest percentage of
      carcasses was contaminated during the first year of the survey (70.5%) whereas in
      the last year (2013) only 36.3% of broilers contained these bacteria.
      Antimicrobial resistance analysis showed that overall 939 (81.6%) of isolates
      were resistant to ciprofloxacin, 646 (56.1%) to tetracycline but only 28 (2.4%)
      to erythromycin. Significant differences in resistance profiles between C. jejuni
      and C. coli were observed with greater resistance level observed in the latter
      species. Furthermore, a significant increase in the percentage of C. jejuni
      resistant to ciprofloxacin (from 59.6% in 2009 to 85.9% in 2014) and to
      tetracycline (from 23.2% to 70.4%, respectively) was identified. Only 20 (1.7%)
      Campylobacter isolates displayed a multiresistance pattern.

PMID- 25846927
TI  - Synergistic antimicrobial activity of caprylic acid in combination with citric
      acid against both Escherichia coli O157:H7 and indigenous microflora in carrot
      juice.
AB  - The identification of novel, effective, and non-thermal decontamination methods
      is imperative for the preservation of unpasteurized and fresh vegetable juices.
      The aim of this study was to examine the bactericidal effects of caprylic acid +
      citric acid against the virulent pathogen Escherichia coli O157:H7 and the
      endogenous microflora in unpasteurized fresh carrot juice. Carrot juice was
      treated with either caprylic acid, citric acid, or a combination of caprylic acid
      + citric acid at mild heating temperature (45  degrees C or 50  degrees C). The
      color of the treated carrot juice as well as microbial survival was examined over
      time. Combined treatment was more effective than individual treatment in terms of
      both color and microbial survival. Caprylic acid + citric acid treatment (each at
      5.0 mM) at 50  degrees C for 5 min resulted in 7.46 and 3.07 log CFU/ml
      reductions in the E. coli O157:H7 and endogenous microflora populations,
      respectively. By contrast, there was no apparent reduction in either population
      following individual treatment. A validation assay using a low-density E. coli
      O157:H7 inoculum (3.31 log CFU/ml) showed that combined treatment with caprylic
      acid (5.0 mM) + citric acid (2.5 mM) at 50  degrees C for >5 min or with caprylic
      acid + citric acid (both at 5.0 mM) at either 45  degrees C or 50  degrees C for
      >5 min completely destroyed the bacteria. Combined treatment also increased the
      redness of the juice, which is a perceived indication of quality. Taken together,
      these results indicate that combined treatment with low concentrations of
      caprylic acid and citric acid, which are of biotic origin, can eliminate
      microorganisms from unpasteurized carrot juice.

PMID- 25846928
TI  - Assessment of microbial risk factors and impact of meteorological conditions
      during production of baby spinach in the Southeast of Spain.
AB  - There is a timely need to evaluate the effect agricultural factors and
      meteorological conditions on fresh produce contamination. This study evaluated
      those risk factors and described, for the first time, the distribution of
      indicator microorganisms (Escherichia coli, Enterococcus, coliforms, and
      Enterobacteriaceae) and the prevalence of foodborne pathogens (Enterohaemorrhagic
      E. coli, Listeria monocytogenes and Salmonella spp.) in baby spinach grown in the
      Southeast of Spain. A longitudinal study was conducted on three farms (2011
      2013). Results obtained for E. coli highlighted soil and irrigation water as
      important factors affecting the microbial safety of baby spinach. Significant
      differences in the proportion of E. coli positive samples were found between
      treated (46.1%) and untreated (100%) irrigation water. However, the microbial
      quality of irrigation water didn't affect E. coli prevalence in produce. All E.
      coli positive spinach samples were detected at the highest observed temperature
      range suggesting that ambient temperature affects the probability and extent of
      spinach contamination. Salmonella spp. was detected by RT-PCR in manure, soil,
      irrigation water and baby spinach but only two of them (manure and irrigation
      water) were confirmed by isolation in culture media. Salmonella RT-PCR positive
      samples showed higher levels of E. coli than Salmonella negative samples. This
      preliminary finding supports recent identification of E. coli as a suitable
      parameter for the hygiene criterion at the primary production of leafy greens.

PMID- 25846929
TI  - Microbiological and chemical characteristics of taruba, an indigenous beverage
      produced from solid cassava fermentation.
AB  - The aim of this work was to identify and characterize the microbiota present
      during fermentation and in the final beverage, taruba, by culture-dependent and 
      independent methods. In addition, target chemical compounds (carbohydrates,
      organic acids, and ethanol) were evaluated. Lactic acid bacteria (LAB) and
      mesophilic bacteria were the predominant microorganisms. Among them,
      Lactobacillus plantarum, Lactobacillus brevis, Leuconostoc mesenteroides, and
      Bacillus subtilis were frequently isolated and detected by DGGE analysis.
      Torulaspora delbrueckii was the dominant yeast species. Yeast isolates Pichia
      exigua, Candida rugosa, T. delbrueckii, Candida tropicalis, Pichia kudriavzevii,
      Wickerhamomyces anomalus, and Candida ethanolica and bacteria isolates Lb.
      plantarum, Bacillus subtilis, Bacillus amyloliquefaciens, Bacillus licheniformis,
      Bacillus sp., and Chitinophaga terrae showed amylolytic activity. Only isolates
      of P. exigua and T. delbrueckii and all species of the genus Bacillus identified
      in this work exhibited proteolytic activity. All microbial isolates grew at 38 
      degrees C, and only the isolates belonging to Hanseniaspora uvarum species did
      not grow at 42  degrees C. These characteristics are important for further
      development of starter cultures; isolates of T. delbrueckii, P. exigua, and
      Bacillus species identified in this work displayed all of these properties and
      are potential strains for use as starter culture in cassava fermented food.

PMID- 25846930
TI  - Effect of sulfur dioxide fumigation on survival of foodborne pathogens on table
      grapes under standard storage temperature.
AB  - We examined the fate of Listeria monocytogenes, Escherichia coli O157:H7, and
      Salmonella enterica Thompson inoculated on freshly-harvested table grapes under
      standard cold storage with initial and weekly sulfur dioxide (SO2) fumigation. L.
      monocytogenes and S. enterica Thompson were much more sensitive to cold
      temperature than E. coli O157:H7. Furthermore, L. monocytogenes was highly
      susceptible to SO2. Initial fumigation with 100 or 200 ppm-hr was sufficient to
      eliminate this pathogen on grapes with low (10(4) cells/grape) and high (10(6)
      cells/grape) inocula, respectively. Initial fumigation with 300 ppm-hr reduced S.
      enterica Thompson population about 300- and 10-fold on grapes with low and high
      inocula, respectively. Initial fumigation with 300 ppm-hr reduced E. coli O157:H7
      population to less than 10-fold, regardless of inoculum density. When grapes were
      inoculated with the high inoculum and fumigated on days 0 and 7 with 200 or 300
      ppm-hr SO2, S. enterica Thompson and E. coli O157:H7 were completely inactivated
      between days 8 and 14 of cold storage. Standard cold storage combined with SO2
      fumigation was effective in reducing and eliminating all three pathogens on table
      grapes, however, depending on the dose, two or three fumigations were needed for
      elimination of S. enterica Thompson and E. coli O157:H7.

PMID- 25846931
TI  - Effect of salt on cell viability and membrane integrity of Lactobacillus
      acidophilus, Lactobacillus casei and Bifidobacterium longum as observed by flow
      cytometry.
AB  - The aim of the current study was to investigate the effect of varying sodium
      chloride concentrations (0-5%) on viability and membrane integrity of three
      probiotic bacteria, Lactobacillus acidophilus, Lactobacillus casei and
      Bifidobacterium longum, using conventional technique and flow cytometry. Double
      staining of cells by carboxyfluorescein diacetate (cFDA) and propidium iodide
      (PI) enabled to evaluate the effect of NaCl on cell esterase activity and
      membrane integrity. Observations from conventional culture technique were
      compared with findings from flow cytometric analysis on the metabolic activities
      of the cells and a correlation was observed between culturability and dye
      extrusion ability of L. casei and B. longum. However, a certain population of L.
      acidophilus was viable as per the plate count method but its efflux activity was
      compromised. Esterase activity of most bacteria reduced significantly (P < 0.05)
      during one week storage at NaCl concentrations greater than 3.5%. The study
      revealed that L. casei was least affected by higher NaCl concentrations among the
      three probiotic bacteria, as opposed to B. longum where the cF extrusion
      performance was greatly reduced during 1 wk storage. The metabolic activity and
      salt resistance of L. casei was found to be highest among the bacteria studied.

PMID- 25846932
TI  - Survival of pathogenic enterohemorrhagic Escherichia coli (EHEC) and control with
      calcium oxide in frozen meat products.
AB  - This study investigated both the level of microbial contamination and the
      presence of enterohemorrhagic Escherichia coli (EHEC) in frozen meat products,
      followed by the evaluation of its survival over 180 days under frozen
      temperature. We also examined the effect of calcium oxide on the populations of
      EHEC, E. coli O157:H7 and EPEC under both 10  degrees C and -18  degrees C
      storage conditions. Afterward, the morphological changes occurring in EHEC cells
      in response to freezer storage temperature and calcium oxide (CaO) treatments
      were examined using transmission electron microscopy. Among the frozen meat
      products tested, the highest contamination levels of total aerobic counts,
      coliforms and E. coli were observed in pork cutlets. Examination showed that 20%
      of the frozen meat products contained virulence genes, including verotoxin (VT) 1
      and 2. Over 180 days of frozen storage and after 3 freeze-thaw cycles, the
      population of EHEC did not change regardless of the type of products or initial
      inoculated concentration, indicating the strong survival ability of EHEC.
      Subsequent testing revealed that the growth of three pathogenic E. coli strains
      was completely inhibited in meat patties prepared with 1% CaO, stored at 10 
      degrees C. However, the addition of 2% CaO was necessary to control the survival
      of EHEC, E. coli O157:H7 and EPEC in meat patties stored at -18  degrees C. CaO
      reduced the population of E. coli O157:H7 more effectively than the other EHEC
      and EPEC strains at both 10  degrees C and -18  degrees C. Transmission electron
      microscopy analysis revealed that exposed EHEC cells were resistant to the
      freezer storage temperature, although some cells incurred injury and death after
      several freeze-thaw cycles. Most of the cells exposed to CaO were found to have
      died or lost their cellular integrity and membranes, indicating that CaO has the
      potential to be used as a powerful antimicrobial agent for manufacturing frozen
      meat products.

PMID- 25846933
TI  - Comparison of homo- and heterofermentative lactic acid bacteria for
      implementation of fermented wheat bran in bread.
AB  - Despite its potential health benefits, the integration of wheat bran into the
      food sector is difficult due to several adverse technological and sensory
      properties such as bitterness and grittiness. Sourdough fermentation is a
      promising strategy to improve the sensory quality of bran without inducing severe
      changes to the bran matrix. Therefore, identification of species/strains with
      potential for industrial sourdough fermentations is important. We compared the
      effects of different representatives of species of lactic acid bacteria (LAB) on
      wheat bran. Lactobacillus plantarum, Lactobacillus pentosus, Lactobacillus
      brevis, Lactobacillus sanfranciscensis and Fructobacillus fructosus produced
      highly individual fermentation patterns as judged from carbohydrate consumption
      and organic acid production. Interestingly, fructose was released during all bran
      fermentations and possibly influenced the fermentation profiles of obligately
      heterofermentative species to varying degrees. Except for the reduction of
      ferulic acid by L. plantarum and L. pentosus, analyses of phenolic compounds and
      alkylresorcinols suggested that only minor changes thereof were induced by the
      LAB metabolism. Sensory analysis of breads baked with fermented bran did not
      reveal significant differences regarding perceived bitterness and aftertaste. We
      conclude that in addition to more traditionally used sourdough species such as L.
      sanfranciscensis and L. brevis, also facultatively heterofermentative species
      such as L. plantarum and L. pentosus possess potential for industrial wheat bran
      fermentations and should be considered in further investigations.

PMID- 25846934
TI  - Mathematical model for viral depuration kinetics in shellfish: an useful tool to
      estimate the risk for the consumers.
AB  - Enteric virus depuration from shellfish is a complex biological process that may
      be influenced by biological properties of the mollusc and/or virus species. On
      the basis of previous experimental data, a mathematical model was developed to
      characterize the kinetics of viral elimination during the depuration process. The
      experimental data consisted on twenty depuration trials, each with 60 kg of
      Manila clams (Venerupis philippinarum) and mediterranean mussels (Mytilus
      galloprovincialis) previously subjected to bioaccumulation with HAV or MNV-1 (as
      a surrogate for human norovirus), that were performed in an experimental
      depuration system during 7 days. It was observed that although viral loads decay
      along depuration, a residual viral load remains at the end of the process
      suggesting a decomposition of viral load in a diluted load (susceptible of
      depuration) and a non-diluted load (unavailable to depurate). The model yielded a
      general equation, which can predict the viral load at any depuration time knowing
      the specific filtration rate, dependent on the bivalve species, and specific
      viral properties. The mathematical model can be combined with quantitative risk
      assessment calculations to determine the safety of the depurated shellfish, which
      can be very helpful not only for shellfish producers but also to public health
      authorities.

PMID- 25846935
TI  - A gaseous acetic acid treatment to disinfect fenugreek seeds and black pepper
      inoculated with pathogenic and spoilage bacteria.
AB  - Contamination of spices by pathogenic and/or spoilage bacteria can be deleterious
      to consumer's health and cause deterioration of foods, and inactivation of such
      bacteria is necessary for the food industry. The present study examined the
      effect of gaseous acetic acid treatment in reducing Escherichia coli O157:H7,
      Salmonella Enteritidis and Bacillus subtilis populations inoculated on fenugreek
      seeds and black pepper. Treatment with gaseous acetic acid at 0.3 mmol/L, 0.6
      mmol/L and 4.7 mmol/L for 1-3 h significantly reduced the populations of E. coli
      O157:H7 and Salmonella Enteritidis on black pepper and fenugreek seeds at 55 
      degrees C (p < 0.05). The gas treatments at 4.7 mmol/L were more effective in
      inactivating the pathogens than the treatment at 0.3 mmol/L. An approximately 5.0
      log reduction was obtained after 3 h of treatment with 4.7 mmol/L acetic acid. No
      significant reductions in the population of B. subtilis spores inoculated on
      fenugreek seeds and black pepper were obtained after the gas treatments at 0.3
      mmol/L or 0.6 mmol/L (p > 0.05). However, the gas treatment at 4.7 mmol/L
      significantly reduced B. subtilis spores (p < 0.05), and 4.0 log CFU/g and 3.5
      log CFU/g reductions on fenugreek seeds and black pepper, respectively, were
      obtained after 3 h of treatment.

PMID- 25846936
TI  - Inactivation of Shiga toxin-producing Escherichia coli in lean ground beef by
      gamma irradiation.
AB  - In this study the radiation resistance of 40 Shiga Toxin-Producing Escherichia
      coli (STEC) isolates which contained various combinations of the shiga toxin 1
      (stx1), shiga toxin 2 (stx2), intimin (eae), and hemolysin (ehx) genes were
      determined. The STEC were suspended in lean ground beef and irradiated at 4 
      degrees C. D10 values, the radiation dose needed to reduce 1 log (90%) of a
      microorganism, ranged from 0.16 to 0.48 kGy, with a mean of 0.31 kGy for the 40
      isolates. Isolates associated with illness outbreaks had a mean D10 of 0.27 kGy,
      while non-outbreak isolates had a mean D10 of 0.36 kGy (p < 0.05). The presence
      or absence of stx1, stx2, or both stx1 and 2 had no affect on D10 (p > 0.05). The
      presence (0.30 kGy) or absence (0.35 kGy) of ehx had no affect on D10 (p > 0.05).
      However, the mean D10 of isolates lacking eae (0.37 kGy) were significantly
      higher than those containing eae (0.27 kGy) (p < 0.05). There was no difference
      in D10 for isolates lacking eae regardless of whether or not they were associated
      with a foodborne illness outbreak (p > 0.05). It may be possible to use some of
      the STEC isolates which lacked eae, ehx, or both (D10 > 0.30) as avirulent
      surrogates in food irradiation research. The data presented in this study
      provides risk assessors data for metagenomic analysis as well as food and
      radiation processors with valuable information to control of STEC in meat.

PMID- 25846937
TI  - Intrapartum referral from primary to secondary care in the Netherlands: a
      retrospective cohort study on management of labor and outcomes.
AB  - BACKGROUND: In the Dutch maternity care system, primary care midwives provide
      care to low-risk women and refer to obstetricians if risks or complications
      occur. We examined reasons for referral, management of labor, and maternal and
      neonatal outcomes among women who were referred during labor. METHODS: In a
      retrospective cohort study, descriptive analyses were performed on data obtained
      from patient records. Six purposively chosen hospitals in The Netherlands
      participated in the study from June 2011 to February 2012. The study population
      included 600 pregnant women who were referred during labor from primary to
      secondary care. MAIN OUTCOME MEASURES: Reasons for referral, interventions after
      referral, mode of delivery, and maternal and neonatal outcomes. RESULTS: Of women
      who were referred during labor, three out of four women were referred for
      moderate risk indications: request for pain relief (30.5%), meconium-stained
      liquor (25.3%), failure to progress during first stage of labor (14.0%), and
      prolonged ruptured membranes without contractions (12.5%). Of all women, 65.7
      percent had a spontaneous vaginal delivery and 59.7 percent received some kind of
      pain relief. Acute referral, meaning fetal distress, occurred in 5.5 percent. Of
      the newborns, 2.7 percent had an Apgar score of 7 or less after 5 minutes and 1.2
      percent had an umbilical cord pH < 7.05. Postpartum complications occurred among
      11.0 percent of women. CONCLUSION: Women who are referred during labor have a
      high probability of spontaneous vaginal delivery. To improve continuity of care
      and satisfaction for this group of women, management of labor could be continued
      by trained primary care midwives.

PMID- 25846938
TI  - Outflow tract ventricular arrhythmias: An update.
AB  - During the last 20 years, the molecular etiology for many ventricular
      tachyarrhythmias once referred to as "idiopathic," has been elucidated. These
      arrhythmias are due to mutations in ion channels or structural proteins and
      include ventricular tachyarrhythmias due to long and short QT syndromes, Brugada
      syndrome, and catecholaminergic polymorphic ventricular tachycardia (VT).
      However, the basis for the most common form of idiopathic ventricular arrhythmia,
      which originates from right or left ventricular outflow tracts, has remained
      elusive. Although traditionally considered a benign ventricular arrhythmia, it is
      now appreciated that some outflow tract arrhythmias also trigger polymorphic VT
      or sudden cardiac death or result in cardiomyopathy. The current understanding of
      outflow tract arrhythmias will be examined. 

PMID- 25846939
TI  - Understanding Sources of Knowledge for Coaches of Athletes with Intellectual
      Disabilities.
AB  - BACKGROUND: Recent research has investigated development of coaching knowledge;
      however, less research has investigated the development of coaches who coach
      athletes with intellectual disabilities. The purpose of this study was to
      understand how coaches of athletes with intellectual disabilities gain their
      knowledge. METHOD: Forty-five Special Olympics Canada coaches participated in
      structured telephone interviews investigating actual and ideal sources of
      coaching knowledge. Coaching knowledge was categorized across the dimensions of
      competition, organization and training. RESULTS: Coaches primarily learned by
      doing and by consulting with coaching peers. Information about ideal sources of
      coaching knowledge demonstrates that coaches would value structured coaching
      courses, learning from mentors and from administrative support, in addition to
      learning on their own and from peers. DISCUSSION: Results suggest that a broader
      approach to education should be incorporated into coaching athletes with
      intellectual disabilities. Recommendations for achieving such goals are provided.

PMID- 25846940
TI  - Coeliac disease - from genetic and immunological studies to clinical
      applications.
AB  - Coeliac disease is a common and important gastrointestinal disease. It affects at
      least 1%, most Western European populations and in Nordic countries it is even
      more frequent. It is strongly associated with certain Human Leukocyte Antigen-DQ
      genes and triggered by ingestion of wheat gluten and related cereals from rye and
      barley. The diagnosis relies on a combination of clinical signs, serology and
      small intestinal biopsy. Work during the last couple of decades has shown that
      gluten-specific, Human Leukocyte Antigen-DQ-restricted T-cells in the intestinal
      mucosa are of paramount importance in the disease process. The gluten peptides
      are chemically modified by the endogenous enzyme transglutaminase 2, the same
      enzyme that serves as target in today's sensitive serological tests for coeliac
      disease. The increasing knowledge on the disease process allows for development
      of improved diagnosis, patient care and new treatment modalities. 

PMID- 25846941
TI  - Enzyme activities of Arabidopsis inositol polyphosphate kinases AtIPK2alpha and
      AtIPK2beta are involved in pollen development, pollen tube guidance and
      embryogenesis.
AB  - Inositol polyphosphate kinase (IPK2) is a key component of inositol polyphosphate
      signaling. There are two highly homologous inositol polyphosphate kinases
      (AtIPK2alpha and AtIPK2beta) in Arabidopsis. Previous studies that overexpressed
      or reduced the expression of AtIPK2alpha and AtIPK2beta revealed their roles in
      auxiliary shoot branching, abiotic stress responses and root growth. Here, we
      report that AtIPK2alpha and AtIPK2beta act redundantly during pollen development,
      pollen tube guidance and embryogenesis. Single knock-out mutants of atipk2alpha
      and atipk2beta were indistinguishable from the wild type, whereas the atipk2alpha
      atipk2beta double mutant could not be obtained. Detailed genetic and cytological
      investigations showed that the mutation of AtIPK2alpha and AtIPK2beta resulted in
      severely reduced transmission of male gametophyte as a result of abnormal pollen
      development and defective pollen tube guidance. In addition, the early embryo
      development of the atipk2alpha atipk2beta double mutant was also aborted.
      Expressing either catalytically inactive or substrate specificity-altered
      variants of AtIPK2beta could not rescue the male gametophyte and embryogenesis
      defects of the atipk2alpha atipk2beta double mutant, implying that the kinase
      activity of AtIPK2 is required for pollen development, pollen tube guidance and
      embryogenesis. Taken together, our results provide genetic evidence for the
      requirement of inositol polyphosphate signaling in plant sexual reproduction.

PMID- 25846942
TI  - Iridium-mediated C-S bond activation and transformation: organoiridium(III)
      thioether, thiolato, sulfinato and thiyl radical compounds. Synthesis,
      mechanistic, spectral, electrochemical and theoretical aspects.
AB  - An attractive methodology, single-electron transfer (SET) reductive cleavage of
      the C-S bond mediated by a metal in the presence of the external stimuli PPh3,
      has been applied to the kinetically inert IrCl3 in order to synthesize the
      thiolato complex [Ir(III)(L(S))Cl(PPh3)2] 3 from precursor thioether complexes
      [Ir(III)(L(SR))Cl2(PPh3)] (R = alkyl) 2. The aforesaid cleavage process in
      association with (arene)C-H activation furnishes a new class of organosulfur
      compounds of iridium(III). The thiolato chelate 3 displays a reversible oxidative
      wave at 0.75 V vs. Ag/AgCl signifying its remarkable nucleophilic character. The
      high electron density on the thiolato-S vis-a-vis superior nucleophilicity can be
      envisaged through the formation of a number of S-centered derivatives. This
      observation has been corroborated with the nature of HOMO in 3, which assumes 49%
      of S(3p). Notably, the facile oxidative nature of 3 makes it an apposite
      precursor for metal-stabilized thiyl radical species. Indeed, iridium(III)
      stabilized 3(+) can be generated by chemical/electrochemical means. The axial EPR
      spectra with g ~ 2.0 along with theoretical analysis of SOMO (S(3p) 24% + Ph(pi)
      43% + d(yz) 15%) and spin density (rho(S) = +0.543, rho(Ph) = +0.315, rho(Ir) =
      +0.151) of one-electron oxidized 3(+) validate the iridium-stabilized thiyl
      radical description. This observation suggests that the CNS coordination mode in
      thiophenolato complex 3 is redox-active. Complex 3 is very prone to S-centered
      oxidation under normal aerobic conditions to yield metallosulfoxide
      [Ir(III)(L(SO2))Cl(PPh3)2] 4. The enhanced nucleophilicity of thiolato-S can also
      be manifested via the smooth S-C bond making process with alkyl halides (R'X, R'
      = Me and allyl; X = Br, I) and subsequent formation of thioether complexes of
      type [Ir(III)(L(SR'))ClX(PPh3)] 5. The organosulfur compounds of iridium(III)
      exhibit rich spectral properties including luminescence and the origin of these
      transitions is scrutinized with DFT and TD-DFT methods.

PMID- 25846943
TI  - Can feeding-swallowing difficulties in children predict language impairments?

PMID- 25846944
TI  - Interleukin-32 stimulates osteosarcoma cell invasion and motility via AKT pathway
      mediated MMP-13 expression.
AB  - As a pro-inflammatory cytokine, interleukin-32 (IL-32) is reported to play an
      important role in tumor development and progression. However, its effects on the
      invasion and motility of osteosarcoma cells remain elusive. The aim of the
      present study was to determine the molecular mechanisms of IL-32 in osteosarcoma
      cells using RT-PCR and western blot analysis. The results showed that IL-32
      stimulation dose-dependently promoted the invasion and motility of osteosarcoma
      cells. Knockdown of endogenous IL-32 by siRNA inhibited osteosarcoma cell
      invasion and motility. Moreover, IL-32 induced the activation of AKT in a time
      dependent manner. IL-32 stimulation was also capable of increasing the expression
      and secretion of matrix metalloproteinase (MMP)-13, which is involved in tumor
      invasion and metastasis. In addition, blockade of AKT activation suppressed IL-32
      mediated invasion, motility and MMP-13 upregulation in osteosarcoma cells. Taken
      together, our results suggest that IL-32 stimulation promotes the invasion and
      motility of osteosarcoma cells, possibly via the activation of AKT and the
      upregulation of MMP-13 expression. Thus, IL-32 may serve as a marker for
      diagnosis, as well as for the treatment of osteosarcoma.

PMID- 25846945
TI  - Plasma concentrations of lidocaine in dogs following lidocaine patch application
      over an incision compared to intact skin.
AB  - The objective was to compare plasma lidocaine concentrations when a commercially
      available 5% lidocaine patch was placed on intact skin vs. an incision. Our
      hypothesis was that greater absorption of lidocaine would occur from the incision
      site compared to intact skin. Ten dogs were used in a crossover design. A patch
      was placed over an incision, and then after a washout period, a patch was placed
      over intact skin. Plasma lidocaine concentrations were measured at patch
      placement; 20, 40 and 60 min; and 2, 4, 6, 12, 24, 36, 48, 72 and 96 h after
      patch placement. After patch removal, the skin was graded using a subjective skin
      reaction system. No dogs required rescue analgesia, and no toxicity or skin
      reaction was noted. Mean +/- SD AUC and CMAX were 3054.29 +/- 1095.93 ng.h/mL and
      54.1 +/- 15.84 ng/mL in the Incision Group, and 2269.9 +/- 1037.08 ng.h/mL and
      44.5 +/- 16.34 ng/mL in the No-Incision Group, respectively. The AUC was
      significantly higher in the Incision Group. The results of the study demonstrate
      that the actual body exposure to lidocaine was significantly higher when an
      incision was present compared to intact skin. No adverse effects were observed
      from either treatment. Efficacy was not evaluated. 

PMID- 25846946
TI  - CT AND MRI FEATURES OF CAROTID BODY PARAGANGLIOMAS IN 16 DOGS.
AB  - Carotid body tumors (paragangliomas) arise from chemoreceptors located at the
      carotid bifurcation. In imaging studies, this neoplasm may be confused with other
      neck neoplasms such as thyroid carcinoma. The purpose of this retrospective,
      cross-sectional study was to describe computed tomographic (CT) and magnetic
      resonance imaging (MRI) characteristics of confirmed carotid body tumors in a
      multi-institutional sample of dogs. A total of 16 dogs met inclusion criteria (14
      examined using CT and two with MRI). The most common reason for imaging was a
      palpable cervical mass or respiratory signs (i.e., dyspnea or increased
      respiratory noises). The most commonly affected breed was Boston terrier (n = 5).
      Dogs were predominantly male castrated (n = 10) and the median age was 9 years
      [range 3-14.5]. Most tumors appeared as a large mass centered at the carotid
      bifurcation, with poor margination in six dogs and discrete margins in ten dogs.
      Masses were iso- to hypoattenuating to adjacent muscles in CT images and
      hyperintense to muscles in T1- and T2-weighted MRI. For both CT and MRI, masses
      typically showed strong and heterogeneous contrast enhancement. There was
      invasion into the adjacent structures in 9/16 dogs. In six of these nine dogs,
      the basilar portion of the skull was affected. The external carotid artery was
      entrapped in seven dogs. There was invasion into the internal jugular vein in
      three dogs, and into the external jugular, maxillary, and linguo-facial veins in
      one dog. Imaging characteristics helped explain some clinical presentations such
      as breathing difficulties, Horner's syndrome, head tilt, or facial nerve
      paralysis. 

PMID- 25846948
TI  - Adipose afferent reflex response to insulin is mediated by melanocortin 4 type
      receptors in the paraventricular nucleus in insulin resistance rats.
AB  - BACKGROUND: Adipose afferent reflex (AAR) contributes to sympathetic activation
      and hypertension. Paraventricular nucleus (PVN) plays an important role in AAR
      and sympathetic outflow. The aim of the present study was to determine whether
      PVN mediates AAR response to insulin in a rat model of insulin resistance (IR).
      METHODS: Male Sprague-Dawley rats were randomly divided into Control and IR
      groups. Insulin resistance was induced by supplementing fructose (125 g L(-1) ,
      12 weeks) in the drinking water. Renal sympathetic nerve activity (RSNA) and mean
      arterial pressure (MAP) were recorded in anesthetized rats. AAR was evaluated by
      the RSNA and MAP responses to injection of capsaicin into four sites of right
      inguinal white adipose tissue. RESULTS: Rats in IR group showed a rise in plasma
      noradrenaline (NE), glucose, insulin and triglyceride levels, left ventricular
      weight, systolic blood pressure, homeostasis model assessment of insulin
      resistance (HOMA-IR) and PVN glucose and insulin levels, melanocortin 4 type
      receptors (MC4Rs) protein expression, but not MC3Rs and insulin receptors.
      Compared with Control group, AAR in IR group was significantly enhanced, which
      contributed to the elevation of NE level; and insulin microinjection into the PVN
      or the third ventricle significantly strengthened AAR, which was attenuated by
      pre-treatment with MC4Rs antagonist HS024 and anti-insulin affibody,
      respectively, but not insulin receptors antagonist S961. CONCLUSION: The enhanced
      AAR participates in sympathetic activation in IR, which can be strengthened by
      PVN insulin. PVN MC4Rs mediate the AAR response to insulin in IR, but not MC3Rs
      and insulin receptors.

PMID- 25846949
TI  - Heart rate deflection point during incremental test in competitive agility border
      collies.
AB  - The aim of this study was to determine a heart rate deflection point (HRdp) in
      competitive agility dogs. Fourteen healthy border collies underwent progressive
      incremental treadmill exercise--modified Conconi test protocol. Heart rate was
      continuously recorded, and the HRdp was estimated using two methods: subjective
      and computer aided regression. Maximal heart rate (HRmax), achieved running speed
      at the anaerobic threshold and at the end of test were also determined.
      Statistical analysis showed a very high positive correlation between HRdp
      determined by two methods. The mean HRdp in this research corresponded to 80% of
      HRmax. The wide range of individual HRdp (162-229 BPM) indicates the need of an
      individual approach in assessing physiological parameters. To the authors'
      knowledge, this is the first application of Conconi modified test for estimating
      anaerobic threshold in agility dogs since the standard for dogs is yet
      undetermined. Future studies need to detect the most appropriate and reliable
      technique for its determination as well as its applicability in programming of
      the optimal training intensity.

PMID- 25846950
TI  - Inflammatory cytokine and acute phase protein concentrations in the peripheral
      blood and uterine washings of cows with subclinical endometritis in the late
      postpartum period.
AB  - The aim of the study was to evaluate the concentrations of proinflammatory
      cytokines: tumor necrosis factor (TNF-alpha) and interleukin-6 (IL-6), anti
      inflammatory cytokine interleukin-10 (IL-10), and acute phase proteins (APPs)-
      haptoglobin (Hp) and serum amyloid A (SAA) in serum and uterine washings of cows
      with subclinical endometritis, and compare them to healthy animals. The study was
      performed on 24 cows on day 60 after delivery. The cows were divided into two
      groups based on the results of cytological tests: 12 cows with subclinical
      endometritis and 12 healthy cows. Experimental material consisted of blood serum
      and uterine washings. The levels of the following cytokines in the study material
      were determined with ELISA: TNF-alpha, IL-6, IL-10 and APPs - Hp and SAA. The
      results show that the levels of TNF-alpha (p < 0.01), IL-6, IL-10 as well as SAA
      and Hp were significantly higher in the serum of cows with subclinical
      endometritis compared to the controls (p < 0.001). Uterine washings had
      significantly higher levels of IL-6, IL-10, and Hp in the experimental cows
      compared to the controls (p < 0.001). The demonstrated differences in the
      concentration of cytokines and APP between cows with subclinical endometritis and
      healthy cows, in both the serum and uterine washings, may suggest the usefulness
      of these parameters in the diagnosis of subclinical endometritis in cows in the
      late postpartum period.

PMID- 25846951
TI  - Nominal and functional task difficulty in skill acquisition: Effects on
      performance in two tests of transfer.
AB  - The influence of nominal and functional task difficulty during the acquisition of
      a motor skill was examined in two tests of transfer of learning. The task
      involved a ballistic, target-directed, finger action. Nominal task difficulty was
      defined as the distance of the target from the home position. Functional task
      difficulty was created by manipulating the progression of target distances during
      practice. Based on the challenge point framework (Guadagnoli & Lee, 2004), we
      predicted that practice with a set of targets farther away from the performer
      would benefit from less functional task difficulty, while practice with a closer
      set of targets would benefit from more functional task difficulty. In single-task
      transfer tests, learners who practiced using the high nominal task difficulty
      targets benefitted in terms of persistence of performance over time. In dual-task
      transfer tests, groups with an intermediate combined (nominal and functional)
      task difficulty performed with greater persistence over time on tests of transfer
      than those who practiced with the highest or lowest combined difficulty. Together
      these findings suggest that the influences of nominal and functional task
      difficulty during acquisition are weighted differentially depending upon the
      transfer test context. The challenge point framework does not accurately capture
      this complex relationship in its current form. 

PMID- 25846952
TI  - Gender difference in older adult's utilization of gravitational and ground
      reaction force in regulation of angular momentum during stair descent.
AB  - Angular momentum of the body is a highly controlled quantity signifying
      stability, therefore, it is essential to understand its regulation during stair
      descent. The purpose of this study was to investigate how older adults use
      gravity and ground reaction force to regulate the angular momentum of the body
      during stair descent. A total of 28 participants (12 male and 16 female; 68.5
      years and 69.0 years of mean age respectively) performed stair descent from a
      level walk in a step-over-step manner at a self-selected speed over a custom made
      three-step staircase with embedded force plates. Kinematic and force data were
      used to calculate angular momentum, gravitational moment, and ground reaction
      force moment about the stance foot center of pressure. Women show a significantly
      greater change in normalized angular momentum (0.92Nms/Kgm; p=.004) as compared
      to men (0.45Nms/Kgm). Women produce higher normalized GRF (p=.031) during the
      double support phase. The angular momentum changes show largest backward
      regulation for Step 0 and forward regulation for Step 2. This greater difference
      in overall change in the angular momentum in women may explain their increased
      risk of fall over the stairs.

PMID- 25846953
TI  - Surgical resection for hepatocellular carcinoma: Moving from what can be done to
      what is worth doing.

PMID- 25846954
TI  - Mindfulness training for adolescents: A neurodevelopmental perspective on
      investigating modifications in attention and emotion regulation using event
      related brain potentials.
AB  - Mindfulness training is increasingly being introduced in schools, yet studies
      examining its impact on the developing brain have been scarce. A
      neurodevelopmental perspective on mindfulness has been advocated as a powerful
      tool to enhance our understanding of underlying neurocognitive changes that have
      implications for developmental well-being research and the implementation of
      mindfulness in education. To stimulate more research in the developmental
      cognitive neuroscience of mindfulness, this article outlines possible indexes of
      mindfulness-based change in adolescence, with a focus on event-related brain
      potential (ERP) markers. We provide methodological recommendations for future
      studies and offer examples of research paradigms. We also discuss how mindfulness
      practice could impact on the development of prefrontal brain structures and
      enhance attention control and emotion regulation skills in adolescents, impacting
      in turn on their self-regulation and coping skills. We highlight advantages of
      the ERP methodology in neurodevelopmental research of mindfulness. It is proposed
      that research using established experimental tasks targeting ERP components such
      as the contingent negative variability, N200, error-related negativity and error
      positivity, P300, and late positive potential could elucidate developmentally
      salient shifts in the neural plasticity of the adolescent brain induced by
      mindfulness practice. 

PMID- 25846956
TI  - Multiple host shifts by the emerging honeybee parasite, Varroa jacobsoni.
AB  - Host shifts are a key mechanism of parasite evolution and responsible for the
      emergence of many economically important pathogens. Varroa destructor has been a
      major factor in global honeybee (Apis mellifera) declines since shifting hosts
      from the Asian honeybee (Apis cerana) > 50 years ago. Until recently, only two
      haplotypes of V. destructor (Korea and Japan) had successfully host shifted to A.
      mellifera. In 2008, the sister species V. jacobsoni was found for the first time
      parasitizing A. mellifera in Papua New Guinea (PNG). This recent host shift
      presents a serious threat to world apiculture but also provides the opportunity
      to examine host shifting in this system. We used 12 microsatellites to compare
      genetic variation of V. jacobsoni on A. mellifera in PNG with mites on A. cerana
      in both PNG and surrounding regions. We identified two distinct lineages of V.
      jacobsoni reproducing on A. mellifera in PNG. Our analysis indicated independent
      host shift events have occurred through small numbers of mites shifting from
      local A. cerana populations. Additional lineages were found in the neighbouring
      Papua and Solomon Islands that had partially host shifted to A. mellifera, that
      is producing immature offspring on drone brood only. These mites were likely in
      transition to full colonization of A. mellifera. Significant population structure
      between mites on the different hosts suggested host shifted V. jacobsoni
      populations may not still reproduce on A. cerana, although limited gene flow may
      exist. Our studies provide further insight into parasite host shift evolution and
      help characterize this new Varroa mite threat to A. mellifera worldwide.

PMID- 25846955
TI  - MicroRNA-155 knockout mice are susceptible to Mycobacterium tuberculosis
      infection.
AB  - MicroRNAs (miRNAs) are short, conserved, non-coding RNA molecules that repress
      translation, followed by the decay of miRNA-targeted mRNAs that encode molecules
      involved in cell differentiation, development, immunity and apoptosis. At least
      six miRNAs, including microRNA-155 (miR-155), were up-regulated when born marrow
      derived macrophages from C57BL/6 mice were infected with Mycobacterium
      tuberculosis Erdman. C57BL/6 mice intravenously infected with Erdman showed up
      regulation of miR-155 in livers and lungs. Following infection, miR-155-deficient
      C57BL/6 mice died significantly earlier and had significantly higher numbers of
      CFU in lungs than wild-type mice. Moreover, fewer CD4(+) T cells, but higher
      numbers of monocytes and neutrophils, were present in the lungs of Erdman
      infected miR-155 knockout (miR-155(-/-)) than of wild-type mice. These findings
      indicated that miR-155 plays a critical role in immune responses to M.
      tuberculosis. 

PMID- 25846957
TI  - Effects of pre-eclampsia and fetal growth restriction on C-type natriuretic
      peptide.
AB  - OBJECTIVE: To determine changes in plasma C-type natriuretic peptide (CNP), a
      paracrine product of the vascular endothelium, in pregnancies with vascular
      disorders, and relate these to time of presentation and severity. DESIGN:
      Retrospective nested cases and controls. SETTING: Community study, Auckland New
      Zealand. POPULATION: Screening for Pregnancy Endpoints (SCOPE) data and bio-bank
      of maternal plasma. METHODS: Maternal plasma amino terminal proCNP (NTproCNP) was
      measured by radioimmunoassay in early (14-16 weeks of gestation, and again at 19
      21 weeks of gestation) and late (34-36 weeks of gestation) pregnancy in three
      groups of women (20 per group): pre-eclampsia (pre-eclampsia); gestational
      hypertension (GHT) with small for gestational age (SGA); and uncomplicated
      pregnancy. MAIN OUTCOME MEASURES: Change in NTproCNP and associations with
      concurrent blood pressure, time of case presentation, severity, and infant
      birthweight. RESULTS: Plasma NTproCNP in early pregnancy in women with vascular
      disorders did not differ from those found in controls. In late pregnancy, levels
      in pre-eclampsia (28.8 +/- 2.3 pM) and in GHT with SGA (28.6 +/- 4.8 pM) were
      significantly increased (P = 0.01 and 0.027, respectively) compared with controls
      (21.3 +/- 1 pM). In pre-eclampsia, levels were significantly higher (P < 0.03) at
      14-16 weeks of gestation in women diagnosed prior to 34 weeks of gestation.
      Combining all three groups, associations of NTproCNP with concurrent diastolic
      and mean arterial pressure were found at 34-36 weeks of gestation (r = 0.46). No
      significant associations were identified with birthweight. CONCLUSIONS: CNP
      secretion during gestation is responsive to vascular stress. Plasma NTproCNP
      measurements may have clinical application in late pregnancy in defining the
      different phenotypes associated with pre-eclampsia.

PMID- 25846958
TI  - Soft template strategy to synthesize iron oxide-titania yolk-shell nanoparticles
      as high-performance anode materials for lithium-ion battery applications.
AB  - Yolk-shell-structured nanoparticles with iron oxide core, void, and a titania
      shell configuration are prepared by a simple soft template method and used as the
      anode material for lithium ion batteries. The iron oxide-titania yolk-shell
      nanoparticles (IO@void@TNPs) exhibit a higher and more stable capacity than
      simply mixed nanoparticles of iron oxide and hollow titania because of the unique
      structure obtained by the perfect separation between iron oxide nanoparticles, in
      combination with the adequate internal void space provided by stable titania
      shells. Moreover, the structural effect of IO@void@TNPs clearly demonstrates that
      the capacity retention value after 50 cycles is approximately 4 times that for
      IONPs under harsh operating conditions, that is, when the temperature is
      increased to 80  degrees C. 

PMID- 25846959
TI  - Adult presentation of X-linked Conradi-Hunermann-Happle syndrome.
AB  - Conradi-Hunermann-Happle syndrome, or X-linked dominant chondrodysplasia punctata
      type 2 (CDPX2), is a genodermatosis caused by mutations in EBP. While typically
      lethal in males, females with CDPX2 generally manifest by infancy or childhood
      with variable features including congenital ichthyosiform erythroderma,
      chondrodysplasia punctata, asymmetric shortening of the long bones, and
      cataracts. We present a 36-year-old female with short stature, rhizomelic and
      asymmetric limb shortening, severe scoliosis, a sectorial cataract, and no family
      history of CDPX2. Whole exome sequencing (WES) revealed a p.Arg63del mutation in
      EBP, and biochemical studies confirmed a diagnosis of CDPX2. Short stature in
      combination with ichthyosis or alopecia, cataracts, and limb shortening in an
      adult should prompt consideration of a diagnosis of CDPX2. As in many genetic
      syndromes, the hallmark features of CDPX2 in pediatric patients are not readily
      identifiable in adults. This demonstrates the utility of WES as a diagnostic tool
      in the evaluation of adults with genetic disorders.

PMID- 25846960
TI  - How Clark's nutcrackers (Nucifraga columbiana) weigh geometric cues depends on
      their previous experience.
AB  - Following passive disorientation, Clark's nutcrackers (Nucifraga columbiana)
      learned to search for a hidden food reward located in one corner of a rectangular
      shaped enclosure that contained either identical or distinct features in each
      corner. Identical features allowed for explicit learning of geometric cues,
      whereas distinct features allowed for both explicit learning of featural cues and
      incidental learning of geometric cues. Birds that only learned about geometry
      incidentally (group Distinct) weighed features greater than geometry when the two
      cues were placed in conflict. However, birds that received explicit training with
      geometry, in addition to feature training (groups Distinct-Identical and
      Identical-Distinct), weighed geometry heavier relative to features. Cue
      preference by the birds also depended on the order in which learning was
      experienced; if explicit training with geometry followed that of features (group
      Distinct-Identical), then both geometry and features were weighed equally, but if
      explicit training with geometry training preceded that of features (group
      Identical-Distinct), the birds weighed geometry greater than features. Results
      suggest both a heightened sensitivity to geometric cues by Clark's nutcrackers
      relative to other species of birds and an increased sensitivity to any spatial
      cue (either features or geometry) that has proven both stable and reliable. 

PMID- 25846961
TI  - Relative versus absolute numerical representation in fish: Can guppies represent
      "fourness"?
AB  - In recent years, the use of operant conditioning procedures has shown that
      species as diverse as chimpanzees, honeybees, and mosquitofish can be trained to
      discriminate between sets containing different numbers of objects. However, to
      succeed in this task, subjects can use two different strategies: either select
      the array containing a specific number of items (an absolute numerosity rule), or
      select the set containing the larger (or smaller) quantity of items (a relative
      numerosity rule). In the latter case, subjects need not only be able to judge
      whether two numerosities are equal or different but also be able to order
      numerosities. Here, in two experiments, we address whether fish can perform both
      kinds of judgment by training them with specific numerosities and testing their
      generalization to new numerosity contrasts. In Experiment 1, subjects were
      initially trained to select between visual arrays of 6 and 12 shapes, and were
      then tested with a contrast pairing the previously trained numerosity (either 6
      or 12) with a novel numerosity (respectively, 3 or 24). Spontaneously, subjects
      selected the novel numerosity, in accordance with a relative numerosity rule. The
      second experiment tested whether guppies can also learn to select one specific
      number against all others, if appropriately trained. Fish trained to select an
      array of 4 shapes against several alternatives (4 vs. 1, 4 vs. 2, 4 vs. 8, 4 vs.
      10) learned to recognize the number 4 against all alternatives and proved able to
      generalize their discrimination to novel, more difficult contrasts (4 vs. 3 and 4
      vs. 6 items). In summary, although guppies preferentially opt for relative
      comparisons, they can flexibly learn either relative or absolute decision
      criteria on numerosity stimuli, depending on the context. 

PMID- 25846962
TI  - High similarity of U2 snDNA sequence between A and B chromosomes in the
      grasshopper Abracris flavolineata.
AB  - B chromosomes are frequently enriched for a wide variety of repetitive DNAs.
      Among grasshoppers in the species Abracris flavolineata (Ommatolampidinae) the B
      chromosomes are submetacentric, C-negative and harbor repetitive DNAs such as, U2
      snDNA, C 0 t-1 DNA, two Mariner-like elements and some microsatellites. Here, we
      provide evidence showing the intragenome similarity between the B chromosome and
      the A complement in A. flavolineata, combining analysis of microdissection and
      chromosome painting and B chromosome-specific amplification through polymerase
      chain reaction (PCR) of U2 snDNA. Chromosome painting revealed signals spread
      through the C-negative regions, including the A and B chromosomes. Moreover,
      significant clustered signals forming bands were observed in some A chromosomes,
      and for the B chromosome, significant signals were located on both arms, which
      could be caused by accumulation of repetitive DNA sequences. The C-positive
      regions did not reveal any signals. Sequence comparison of U2 snDNA between that
      obtained from a genome without the B chromosome and that from uB-DNA revealed
      high similarity with the occurrence of four shared haplotypes, one of them (i.e.,
      Hap1) being highly prevalent and putatively ancestral. The highest divergence
      from Hap1 was observed for Hap3, which was caused by only six mutational steps.
      These data support an intraspecific origin of the B chromosome in A. flavolineata
      that is highly similar with the A complement, and the low U2 snDNA sequence
      diversity observed in the B chromosome could be related to its recent origin,
      besides intrachromosomal concerted evolution for U2 snDNA repeats in the B
      chromosome. 

PMID- 25846963
TI  - Genome-wide identification and characterization of aquaporin gene family in
      common bean (Phaseolus vulgaris L.).
AB  - Plant aquaporins are a large and diverse family of water channel proteins that
      are essential for several physiological processes in living organisms. Numerous
      studies have linked plant aquaporins with a plethora of processes, such as
      nutrient acquisition, CO2 transport, plant growth and development, and response
      to abiotic stresses. However, little is known about this protein family in common
      bean. Here, we present a genome-wide identification of the aquaporin gene family
      in common bean (Phaseolus vulgaris L.), a legume crop essential for human
      nutrition. We identified 41 full-length coding aquaporin sequences in the common
      bean genome, divided by phylogenetic analysis into five sub-families (PIPs, TIPs,
      NIPs, SIPs and XIPs). Residues determining substrate specificity of aquaporins
      (i.e., NPA motifs and ar/R selectivity filter) seem conserved between common bean
      and other plant species, allowing inference of substrate specificity for these
      proteins. Thanks to the availability of RNA-sequencing datasets, expression
      levels in different organs and in leaves of wild and domesticated bean accessions
      were evaluated. Three aquaporins (PvTIP1;1, PvPIP2;4 and PvPIP1;2) have the
      overall highest mean expressions, with PvTIP1;1 having the highest expression
      among all aquaporins. We performed an EST database mining to identify drought
      responsive aquaporins in common bean. This analysis showed a significant increase
      in expression for PvTIP1;1 in drought stress conditions compared to well-watered
      environments. The pivotal role suggested for PvTIP1;1 in regulating water
      homeostasis and drought stress response in the common bean should be verified by
      further field experimentation under drought stress. 

PMID- 25846964
TI  - Development of a Hyperactive Primary Hemostatic System During Off-Pump Lung
      Transplantation Resulting From an Unbalance Between von Willebrand Factor and Its
      Cleaving Protease ADAMTS13.
AB  - An unbalance between the platelet-adhesive protein von Willebrand factor (VWF)
      and its cleaving protease ADAMTS13 is a risk factor for thrombosis. Here, we
      assessed levels and functionality of VWF and ADAMTS13 in patients undergoing off
      pump lung transplantation. We analyzed plasma of 10 patients and distinguished
      lung transplantation-specific effects from those generally accompanying open
      chest surgeries by comparing results with 11 patients undergoing off-pump
      coronary bypass graft (CABG) surgery. Forty healthy volunteers were included for
      reference values. VWF antigen levels as well as the VWF ristocetin cofactor
      activity/VWF antigen ratio increased during lung transplantation and after CABG
      surgery. An increase in VWF propeptide levels was paralleled by a decrease in
      ADAMTS13 activity. This was more pronounced during lung transplantation.
      Similarly, the capacity of plasma to support platelet aggregation under shear
      flow conditions in vitro was more increased during lung transplantation. The
      proportion of high molecular weight VWF multimers was elevated in both groups
      without evidence for ultra-large VWF. VWF's collagen binding activity remained
      unchanged. In conclusion, a hyperactive primary hemostatic system develops during
      lung transplantation resulting both from a pronounced (functional) increase of
      the VWF molecule and decrease of ADAMTS13. This may increase the risk of platelet
      thrombosis within the allograft. 

PMID- 25846965
TI  - Enzymes for synthetic biology of ambroxide-related diterpenoid fragrance
      compounds.
AB  - Ambrox and related ambroxides are highly priced in the fragrance industry, and
      valued for their delicate odor and fixative properties. Historically, ambrox was
      obtained from ambergris, a waxy excretion produced by sperm whales, now an
      endangered species. Synthetic ambroxides have replaced ambergris in perfume
      manufacture. Plant labdane diterpenoids can serve as starting material for
      ambroxide synthesis. Among these, the diterpene alcohol sclareol is the major
      industrial precursor obtained from cultivated clary sage (Salvia sclarea). In
      plants, a large family of diterpene synthase (diTPS) enzymes controls key
      reactions in diterpenoid biosynthesis. Advanced metabolite profiling and high
      throughput sequencing of fragrant and medicinal plants have accelerated discovery
      of novel diTPS functions, providing a resource for combinatorial synthetic
      biology and metabolic engineering approaches. This chapter highlights recent
      progress on the discovery, characterization, and engineering of plant diTPSs with
      potential uses in ambroxide production. It features biosynthesis of sclareol, cis
      abienol, and diterpene resin acids, as sources of genes and enzymes for
      diterpenoid bioproducts.

PMID- 25846977
TI  - Canine orbital rhabdomyosarcoma: a report of 18 cases.
AB  - PURPOSE: To describe clinical and pathological features of canine orbital
      rhabdomyosarcoma (COR). METHODS: Retrospective review of patients with COR from
      the archives of the Comparative Ocular Pathology Laboratory of Wisconsin and the
      University of Wisconsin Veterinary Medical Teaching Hospital (1983-2014).
      RESULTS: Eighteen cases of COR were identified, all diagnosed in an 8-year period
      (2006-2014). Affected dogs were typically young (range 1-8; median 2 years), and
      both sexes were equally represented. Common clinical signs included exophthalmos
      (16/18) with dorsolateral deviation of the globe (10/18) and elevation of the
      nictitans (12/18). Ultrasonography, performed in nine cases, revealed an orbital
      mass with mixed echogenicity and posterior globe indentation. Advanced imaging,
      performed in nine cases, demonstrated a soft tissue mass with variable contrast
      enhancement and lysis of the orbital bones (5/9). Histologically, all tumors were
      subclassified as embryonal rhabdomyosarcoma. All neoplasms demonstrated positive
      immunohistochemical labeling for desmin, and 14/18 were positive for skeletal
      muscle actin. Follow-up information was available for 15/18 cases. Older dogs,
      aged 6-8 years, had no clinical signs of recurrence or metastasis 8-13 months
      postdiagnosis (4/4). Most younger dogs (9/11), aged 1-4 years, were euthanized
      within 6 months (median 2.5 months) of diagnosis due to recurrence at the
      surgical site (5/9) and/or metastasis (5/9). CONCLUSIONS: Canine orbital
      rhabdomyosarcoma is a highly malignant neoplasm in juvenile dogs, but may be
      amenable to surgical resection in older dogs. This duality in biologic behavior
      may reflect differences in tissue of origin between juvenile onset tumors and
      adult onset tumors.

PMID- 25846978
TI  - Thermal oxidation of cholesterol: Preliminary evaluation of 2-methyl-6-heptanone
      and 3-methylbutanal as volatile oxidation markers.
AB  - Cholesterol oxidation in food and model systems is usually monitored by
      evaluating cholesterol oxidation products, but the analysis is time-consuming and
      expensive. Therefore, the determination of volatile compounds deriving from
      cholesterol thermoxidation could be valuable to identify other possible oxidation
      markers. Cholesterol alone and in the presence of a triacylglycerol mixture
      (tripalmitin, tristearin, and triolein) were thermoxidized at 170 degrees C for
      15min. In both model systems, the total volatile compounds increased three times
      when oxidation time rose from 5 to 15min. The main classes of volatile compounds
      were aldehydes, ketones, alcohols and hydrocarbons, displaying a similar behavior
      in both systems. After 5min of oxidation, 2-methyl-6-heptanone was the main
      volatile compound, followed by 3-methylpentane, 2,3-dimethyl-1-pentene and 3
      methylbutanal. To verify if 2-methyl-6-heptanone could be used as volatile marker
      of cholesterol oxidation, data were compared with the total cholesterol oxidation
      products content of each system. A significant correlation between total
      cholesterol oxidation products content and 2-methyl-6-heptanone amount was found
      when cholesterol was oxidized alone (r(2)=0.994) and in presence of
      triacylglycerols (r(2)=0.998). When egg yolk was thermoxidized at 80 degrees C
      for 6h, 3-methylbutanal was the volatile compound that better explained the
      oxidative trend in this food system, showing a significant correlation with
      cholesterol oxidation rate (r=0.91). In conclusion, 2-methyl-6-heptanone and 3
      methylbutanal could represent an easy and cheaper strategy for monitoring
      cholesterol oxidation in model systems and food samples, respectively; however, a
      deeper investigation on the amount and type of volatile compounds generated from
      cholesterol oxidation according to the food matrix, should be carried out. 

PMID- 25846979
TI  - Steroid biosynthesis in adipose tissue.
AB  - Tissue-specific expression of steroidogenic enzymes allows the modulation of
      active steroid levels in a local manner. Thus, the measurement of local steroid
      concentrations, rather than the circulating levels, has been recognized as a more
      accurate indicator of the steroid action within a specific tissue. Adipose
      tissue, one of the largest endocrine tissues in the human body, has been
      established as an important site for steroid storage and metabolism. Locally
      produced steroids, through the enzymatic conversion from steroid precursors
      delivered to adipose tissue, have been proven to either functionally regulate
      adipose tissue metabolism, or quantitatively contribute to the whole body's
      steroid levels. Most recently, it has been suggested that adipose tissue may
      contain the steroidogenic machinery necessary for the initiation of steroid
      biosynthesis de novo from cholesterol. This review summarizes the evidence
      indicating the presence of the entire steroidogenic apparatus in adipose tissue
      and discusses the potential roles of local steroid products in modulating adipose
      tissue activity and other metabolic parameters. 

PMID- 25846980
TI  - Positing, fitting, and selecting regression models for pooled biomarker data.
AB  - Pooling biospecimens prior to performing lab assays can help reduce lab costs,
      preserve specimens, and reduce information loss when subject to a limit of
      detection. Because many biomarkers measured in epidemiological studies are
      positive and right-skewed, proper analysis of pooled specimens requires special
      methods. In this paper, we develop and compare parametric regression models for
      skewed outcome data subject to pooling, including a novel parameterization of the
      gamma distribution that takes full advantage of the gamma summation property. We
      also develop a Monte Carlo approximation of Akaike's Information Criterion
      applied to pooled data in order to guide model selection. Simulation studies and
      analysis of motivating data from the Collaborative Perinatal Project suggest that
      using Akaike's Information Criterion to select the best parametric model can help
      ensure valid inference and promote estimate precision.

PMID- 25846981
TI  - Identification of a chronic non-neurodegenerative microglia activation state in a
      mouse model of peroxisomal beta-oxidation deficiency.
AB  - The functional diversity and molecular adaptations of reactive microglia in the
      chronically inflamed central nervous system (CNS) are poorly understood. We
      previously showed that mice lacking multifunctional protein 2 (MFP2), a pivotal
      enzyme in peroxisomal beta-oxidation, persistently accumulate reactive myeloid
      cells in the gray matter of the CNS. Here, we show that the increased numbers of
      myeloid cells solely derive from the proliferation of resident microglia and not
      from infiltrating monocytes. We defined the signature of Mfp2(-/-) microglia by
      gene expression profiling after acute isolation, which was validated by
      quantitative polymerase reaction (qPCR), immunohistochemical, and flow cytometric
      analysis. The features of Mfp2(-/-) microglia were compared with those from
      SOD1(G93A) mice, an amyotrophic lateral sclerosis model. In contrast to the
      neurodegenerative milieu of SOD1(G93A) spinal cord, neurons were intact in Mfp2(
      /-) brain and Mfp2(-/-) microglia lacked signs of phagocytic and neurotoxic
      activity. The chronically reactive state of Mfp2(-/-) microglia was accompanied
      by the downregulation of markers that specify the unique microglial signature in
      homeostatic conditions. In contrast, mammalian target of rapamycin (mTOR) and
      downstream glycolytic and protein translation pathways were induced, indicative
      of metabolic adaptations. Mfp2(-/-) microglia were immunologically activated but
      not polarized to a pro- or anti-inflammatory phenotype. A peripheral
      lipopolysaccharide challenge provoked an exaggerated inflammatory response in
      Mfp2(-/-) brain, consistent with a primed state. Taken together, we demonstrate
      that chronic activation of resident microglia does not necessarily lead to
      phagocytosis nor overt neurotoxicity.

PMID- 25846982
TI  - Race/Ethnicity and Treatment Outcome in a Randomized Controlled Trial for
      Trichotillomania (Hair-Pulling Disorder).
AB  - OBJECTIVE: Treatment outcome was compared among non-Hispanic White and
      racial/ethnic minority participants with trichotillomania (TTM), or hair-pulling
      disorder. METHOD: Symptom severity, quality of life, and TTM-related disability
      were compared in a behavior therapy trial with a stepped care approach: web-based
      self-help and then individual behavior therapy. The sample comprised 72% (n = 38)
      non-Hispanic White participants and 28% (n = 15) minority participants. RESULTS:
      The ethnic groups responded differently to treatment, with fewer minority
      participants showing improvement during web-based self-help. Response rates were
      equivalent between ethnic groups during the in-person behavior therapy. These
      results should be interpreted with caution because of the small sample size of
      minorities in the study and consequent inability to analyze results for each
      racial/ethnic group individually. CONCLUSIONS: Future studies should focus on the
      investigation of factors that may enable or hinder racial and ethnic minority
      participants to benefit from online and/or self-help behavior therapy for TTM.

PMID- 25846983
TI  - Polyhydroxyalkanoate (PHA) storage within a mixed-culture biomass with
      simultaneous growth as a function of accumulation substrate nitrogen and
      phosphorus levels.
AB  - The response of a mixed-microbial-culture (MMC) biomass for PHA accumulation was
      evaluated over a range of relative nitrogen (N) and phosphorus (P) availabilities
      with respect to the supply of either complex (fermented whey permeate - FWP) or
      simpler (acetic acid) organic feedstocks. Fed-batch feed-on-demand PHA
      accumulation experiments were conducted where the feed N/COD and P/COD ratios
      were varied ranging from conditions of nutrient starvation to excess. A feast
      famine enrichment (activated sludge) biomass, produced in a pilot-scale aerobic
      sequencing batch reactor on FWP and with a long history of stable PHA
      accumulation performance, was used for all the experiments as reference material.
      FWP with N/COD ratios of (2, 5, 15, 70 mg/g all with P/COD = 8 mg/g) as well as
      simulated FWP with nutrient starvation (N/COD = P/COD = 0) conditions were
      applied. For the acetic acid accumulations, nutrient starvation as well as N/COD
      variations (2.5, 5, 50 mg/g all with P/COD = 9 mg/g) and P/COD variations (0.5,
      2, 9, 15 mg/g all with N/COD = 10 mg/g) were evaluated. An optimal range of
      combined N and P limitation with N/COD from 2 to 15 mg/g and P/COD from 0.5 to 3
      mg/g was considered to offer consistent improvement of productivity over the case
      of nutrient starvation. Productivity increased due to active biomass growth of
      the PHA storing biomass without observed risk for a growth response overtaking
      PHA storage activity. PHA production with respect to the initial active biomass
      was significantly higher even in cases of excess nutrient additions when compared
      to the cases of nutrient starvation. The 24-h PHA productivities were enhanced as
      much as 4-fold from a base value of 1.35 g-PHA per gram initial active biomass
      with respect nutrient starvation feedstock. With or without nutrient loading the
      biomass consistently accumulated similar and significant PHA (nominally 60% g
      PHA/g-VSS). Based on results from replicate experiments some variability in the
      extant biomass maximum PHA content was attributed to interpreted differences in
      the biomass initial physiological state and not due to changes in feedstock
      nutrient loading. We found that the accumulation process production rates for
      mixed cultures can be sustained long after the maximum PHA content of the biomass
      was reached. Within the specific context of the applied fed-batch feed-on-demand
      methods, active biomass growth was interpreted to have been largely restricted to
      the PHA-storing phenotypic fraction of the biomass. This study suggests practical
      prospects for mixed culture PHA production using a wide range of volatile fatty
      acid (VFA) rich feedstocks. Such VFA sources derived from residual industrial or
      municipal organic wastes often naturally contain associated nutrients ranging in
      levels from limitation to excess.

PMID- 25846984
TI  - Microbial fuel cell biosensor for rapid assessment of assimilable organic carbon
      under marine conditions.
AB  - The development of an assimilable organic carbon (AOC) detecting marine microbial
      fuel cell (MFC) biosensor inoculated with microorganisms from marine sediment was
      successful within 36 days. This established marine MFC was tested as an AOC
      biosensor and reproducible microbiologically produced electrical signals in
      response to defined acetate concentration were achieved. The dependency of the
      biosensor sensitivity on the potential of the electron-accepting electrode
      (anode) was investigated. A linear correlation (R(2) > 0.98) between
      electrochemical signals (change in anodic potential and peak current) and acetate
      concentration ranging from 0 to 150 MUM (0-3600 MUg/L of AOC) was achieved.
      However, the present biosensor indicated a different-linear relation at somewhat
      elevated acetate concentration ranging from 150 to 450 MUM (3600-10,800 MUg/L of
      AOC). This high concentration of acetate addition could be measured by coulombic
      measurement (cumulative charges) with a linear correlation. For the acetate
      concentration detected in this study, the sensor recovery time could be
      controlled within 100 min.

PMID- 25846985
TI  - Regeneration of iron-based adsorptive media used for removing arsenic from
      groundwater.
AB  - Adsorptive media technology is regarded as a simple, low cost method of removing
      arsenic from drinking water particularly for small systems. Currently, when the
      effluent of a treatment system reaches the USEPA maximum contaminant level (MCL)
      of 10 ug/L, the exhausted media is removed and replaced by new virgin media.
      Although the commonly used iron-based media products are reasonable in price, the
      replacement cost accounts for around 80% of the systems total operational costs.
      One option to media replacement is on-site regeneration and reuse of the
      exhausted media. To determine whether an iron based media can be successfully
      regenerated and reused, laboratory batch and column regeneration tests were
      conducted on six exhausted iron-based media products obtained from six full scale
      arsenic removal treatment systems. Batch tests conducted on three of the media
      products to evaluate the effectiveness of 1-6% caustic regenerant solutions found
      that arsenic desorption increased until around 4%. Using 4% caustic solutions,
      the columns tests on the six exhausted media products showed arsenic removals
      ranged from 25 to 90% with the best results obtained with the Severn Trent E33
      media. Exposing the media to caustic (pH >= 13) and acid (pH <= 2) solutions
      found minimal media loss with the caustic solution, but significant media
      dissolution with a pH 2 acid solution. A six column pilot plant test at an Ohio
      test site with the lab regenerated media products found that the regenerated
      media could achieve arsenic removals somewhat similar to virgin media.

PMID- 25846986
TI  - Animal models of Epstein Barr virus infection.
AB  - Epstein Barr virus (EBV) was the first human tumor virus to be described. Despite
      its discovery now more than fifty years ago, immune control of this virus is
      still not very well understood and no vaccine is available. This knowledge gap is
      due in part to the lack of a preclinical small animal model which can faithfully
      recapitulate EBV infection and immune control, and would allow testing of EBV
      specific vaccine candidates. With the advent of mice with reconstituted human
      immune system compartments (HIS mice) during the past decade this is changing. We
      will discuss which aspects of EBV infection and its immune control can already be
      modeled in HIS mice, and which shortcomings still need to be overcome in order to
      recapitulate the immunobiology of oncogenic EBV infection. 

PMID- 25846987
TI  - Oncolytic bovine herpesvirus type 1 as a broad spectrum cancer therapeutic.
AB  - Oncolytic viruses selectively replicate in tumor cells and elicit antitumor
      effects in vivo by both direct and indirect methods. They are attractive avenues
      of cancer therapy due to the absence of toxic side effects often seen in current
      treatment modalities. Bovine herpesvirus type 1 (BHV-1) holds promise as a broad
      spectrum oncolytic vector that is able to infect and kill human tumor cells from
      a variety of histological origins, including cancer-initiating cells. In the
      majority of cases, BHV-1 elicits tumor cell death in the absence of a productive
      infection. In vivo, BHV-1 affects the incidence of secondary lesions in cotton
      rats bearing subcutaneous breast adenocarcinomas. These recent studies contribute
      to the characterization of BHV-1 as an oncolytic virus. 

PMID- 25846988
TI  - Potentiating oncolytic viral therapy through an understanding of the initial
      immune responses to oncolytic viral infection.
AB  - Despite the challenge of implementing oncolytic viral therapy into mainstream
      clinical use, the obstacles of early clinical trials have outlined numerous areas
      requiring additional investigation. In particular, the role of innate and
      adaptive immunity has received significant attention in this context. It is
      increasingly clear that a one-sided approach of either immune suppression or
      robust immune cell activation is not the answer for clinical success. Rather,
      recent studies are increasingly demonstrating the delicate balance between both
      anti-viral immune suppression and immune mediated tumor killing. In this review
      we focus on aspects of innate immune cell activation following oncolytic viral
      infection and how this response has the potential of bridging to the broader goal
      of viral mediated immunotherapy. 

PMID- 25846993
TI  - Conflict management style, supportive work environments and the experience of
      work stress in emergency nurses.
AB  - AIMS: To examine the conflict management style that emergency department (ED)
      nurses use to resolve conflict and to determine whether their style of managing
      conflict and a supportive work environment affects their experience of work
      stress. BACKGROUND: Conflict is a common stressor that is encountered as nurses
      strive to achieve patient satisfaction goals while delivering quality care. How a
      nurse perceives support may impact work stress levels and how they deal with
      conflict. METHODS: A correlational design examined the relationship between
      supportive work environment, and conflict management style and work stress in a
      sample of 222 ED nurses using the expanded nurse work stress scale; the survey of
      perceived organisational support; and the Rahim organisational conflict inventory
      II. RESULTS: Twenty seven percent of nurses reported elevated levels of work
      stress. A supportive work environment and avoidant conflict management style were
      significant predictors of work stress. CONCLUSIONS: Findings suggest that ED
      nurses' perception of a supportive work environment and their approach to
      resolving conflict may be related to their experience of work stress.
      IMPLICATIONS FOR NURSING MANAGEMENT: Providing opportunities for ED nurses in
      skills training in constructive conflict resolution may help to reduce work
      stress and to improve the quality of patient care.

PMID- 25846994
TI  - Regional movement patterns of a small-bodied shark revealed by stable-isotope
      analysis.
AB  - This study used stable-isotope analysis to define the nearshore regional
      residency and movements of the small-bodied Australian sharpnose shark
      Rhizoprionodon taylori. Plasma and muscle delta(13) C and delta(15) N of R.
      taylori were collected from across five embayments and compared with values of
      seagrass and plankton from each bay. Linear distances between adjacent bays
      ranged from 30 to 150 km. There was a positive geographic correlation between R.
      taylori tissue and environmental delta(13) C values. Populations with the highest
      tissue delta(15) N were collected from bays that had the highest environmental
      delta(15) N values. These results suggest that R. taylori did not forage more
      than 100 km away from their capture location within 6 months to 1 year. The
      successful application of isotope analysis to define R. taylori movement
      demonstrates that this technique may be used in addition to traditional methods
      to study the movement of sharks, even within similar habitats across regionally
      small spatial scales (<100 km). 

PMID- 25846995
TI  - Quality improvement in neurology: Epilepsy Update Quality Measurement Set.

PMID- 25846996
TI  - MRI detection of prion protein plaques in variant Creutzfeldt-Jakob disease.

PMID- 25846997
TI  - Owl's eye sign: A rare neuroimaging finding in flail arm syndrome.

PMID- 25846998
TI  - Quantitative susceptibility mapping suggests a paramagnetic effect in PML.

PMID- 25846999
TI  - Opioids for chronic noncancer pain: A position paper of the American Academy of
      Neurology.

PMID- 25847000
TI  - Clinical Reasoning: A 57-year-old woman who developed acute amnesia following
      fever and upper respiratory symptoms.

PMID- 25847001
TI  - Teaching NeuroImages: Primary dural mucosa-associated lymphoid tissue lymphoma.

PMID- 25847002
TI  - Teaching NeuroImages: Acute neurologic deficits due to Balo concentric sclerosis.

PMID- 25847003
TI  - 3D Modeling of dengue virus NS4B and Chikungunya virus nsP4: identification of a
      common drug target and designing a single antiviral inhibitor.
AB  - Dengue and chikungunya virus infections are one of the major causes of morbidity
      and mortality in tropical and sub-tropical regions of the world. These two
      viruses belong to two different families with many similarities and
      dissimilarities. Both are enveloped viruses and the mode of transmission is also
      by the same mosquito species. Especially in case of symptom expression, there is
      confusion between these two viruses. Reports indicate the overlapping endemic
      areas and co-infections of both viruses in a single patient. The above factors
      indicate that there is a need for developing a single drug/vaccine for both the
      viruses. As a first report in this direction, we have used the bioinformatics
      tools to identify a common target in both the viruses for a single inhibitor
      molecule. Phylogenetic and distance based analyses using the nucleotide sequences
      of arthropod and non-arthropod borne viruses indicated a common origin of
      evolutionary point for mosquito borne viruses, irrespective of their families.
      Similarly, the amino acid sequences of non-structural protein-4B (NS4B) of dengue
      virus and non-structural protein-P4 (nsP4) of chikungunya virus showed a common
      evolutionary origin. Modeled and superimposed 3D-structures of above two proteins
      showed a common alpha helix. Virtual screening of selected molecules was done to
      identify the molecules which can bind to the identified common helix and found
      that N-(p-tolylmethyl)-3-[(3-pyridylmethylamino)methyl]benzamide (TPB) has
      significant binding characteristics to the common helix. Molecular simulations
      indicated that both the protein-TPB complexes were stable. Therefore, we propose
      that TPB or its analogues could act as antiviral agents against both the viruses.

PMID- 25847004
TI  - The bZIP transcription factor PfZipA regulates secondary metabolism and oxidative
      stress response in the plant endophytic fungus Pestalotiopsis fici.
AB  - The bZIP transcription factors are conserved in all eukaryotes and play critical
      roles in organismal responses to environmental challenges. In filamentous fungi,
      several lines of evidence indicate that secondary metabolism (SM) is associated
      with oxidative stress mediated by bZIP proteins. Here we uncover a connection
      with a bZIP protein and oxidative stress induction of SM in the plant endophytic
      fungus Pestalotiopsis fici. A homology search of the P. fici genome with the bZIP
      protein RsmA, involved in SM and the oxidative stress response in Aspergillus
      nidulans, identified PfZipA. Deletion of PfzipA resulted in a strain that
      displayed resistant to the oxidative reagents tert-butylhydroperoxide (tBOOH),
      diamide, and menadione sodium bisulfite (MSB), but increased sensitivity to H2O2
      as compared to wild type (WT). Secondary metabolite production presented a
      complex pattern dependent on PfzipA and oxidative reagents. Without oxidative
      treatment, the DeltaPfzipA strain produced less isosulochrin and ficipyroneA than
      WT; addition of tBOOH further decreased production of iso-A82775C and
      pestaloficiol M in DeltaPfzipA; diamide treatment resulted in equivalent
      production of isosulochrin and ficipyroneA in the two strains; MSB treatment
      further decreased production of RES1214-1 and iso-A82775C but increased
      pestaloficiol M production in the mutant; and H2O2 treatment resulted in enhanced
      production of isosulochrin, RES1214-1 and pestheic acid but decreased ficipyroneA
      and pestaloficiol M in DeltaPfzipA compared to WT. Our results suggest that
      PfZipA regulation of SM is modified by oxidative stress pathways and provide
      insights into a possible role of PfZipA in mediating SM synthesis in the
      endophytic lifestyle of P. fici. 

PMID- 25847005
TI  - MetaMapR: pathway independent metabolomic network analysis incorporating
      unknowns.
AB  - Metabolic network mapping is a widely used approach for integration of
      metabolomic experimental results with biological domain knowledge. However,
      current approaches can be limited by biochemical domain or pathway knowledge
      which results in sparse disconnected graphs for real world metabolomic
      experiments. MetaMapR integrates enzymatic transformations with metabolite
      structural similarity, mass spectral similarity and empirical associations to
      generate richly connected metabolic networks. This open source, web-based or
      desktop software, written in the R programming language, leverages KEGG and
      PubChem databases to derive associations between metabolites even in cases where
      biochemical domain or molecular annotations are unknown. Network calculation is
      enhanced through an interface to the Chemical Translation System, which allows
      metabolite identifier translation between >200 common biochemical databases.
      Analysis results are presented as interactive visualizations or can be exported
      as high-quality graphics and numerical tables which can be imported into common
      network analysis and visualization tools. AVAILABILITY AND IMPLEMENTATION: Freely
      available at http://dgrapov.github.io/MetaMapR/. Requires R and a modern web
      browser. Installation instructions, tutorials and application examples are
      available at http://dgrapov.github.io/MetaMapR/. CONTACT: ofiehn@ucdavis.edu.

PMID- 25847006
TI  - Stratifying tumour subtypes based on copy number alteration profiles using next
      generation sequence data.
AB  - MOTIVATION: The role of personalized medicine and target treatment in the
      clinical management of cancer patients has become increasingly important in
      recent years. This has made the task of precise histological substratification of
      cancers crucial. Increasingly, genomic data are being seen as a valuable
      classifier. Specifically, copy number alteration (CNA) profiles generated by next
      generation sequencing (NGS) can become a determinant for tumours subtyping. The
      principle purpose of this study is to devise a model with good prediction
      capability for the tumours histological subtypes as a function of both the
      patients covariates and their genome-wide CNA profiles from NGS data. RESULTS: We
      investigate a logistic regression for modelling tumour histological subtypes as a
      function of the patients' covariates and their CNA profiles, in a mixed model
      framework. The covariates, such as age and gender, are considered as fixed
      predictors and the genome-wide CNA profiles are considered as random predictors.
      We illustrate the application of this model in lung and oral cancer datasets, and
      the results indicate that the tumour histological subtypes can be modelled with a
      good fit. Our cross-validation indicates that the logistic regression exhibits
      the best prediction relative to other classification methods we considered in
      this study. The model also exhibits the best agreement in the prediction between
      smooth-segmented and circular binary-segmented CNA profiles. AVAILABILITY AND
      IMPLEMENTATION: An R package to run a logistic regression is available in
      http://www1.maths.leeds.ac.uk/~arief/R/CNALR/. CONTACT: a.gusnanto@leeds.ac.uk
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 25847007
TI  - EBSeq-HMM: a Bayesian approach for identifying gene-expression changes in ordered
      RNA-seq experiments.
AB  - MOTIVATION: With improvements in next-generation sequencing technologies and
      reductions in price, ordered RNA-seq experiments are becoming common. Of primary
      interest in these experiments is identifying genes that are changing over time or
      space, for example, and then characterizing the specific expression changes. A
      number of robust statistical methods are available to identify genes showing
      differential expression among multiple conditions, but most assume conditions are
      exchangeable and thereby sacrifice power and precision when applied to ordered
      data. RESULTS: We propose an empirical Bayes mixture modeling approach called
      EBSeq-HMM. In EBSeq-HMM, an auto-regressive hidden Markov model is implemented to
      accommodate dependence in gene expression across ordered conditions. As
      demonstrated in simulation and case studies, the output proves useful in
      identifying differentially expressed genes and in specifying gene-specific
      expression paths. EBSeq-HMM may also be used for inference regarding isoform
      expression. AVAILABILITY AND IMPLEMENTATION: An R package containing examples and
      sample datasets is available at Bioconductor. CONTACT: kendzior@biostat.wisc.edu
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 25847008
TI  - Gene selection for the reconstruction of stem cell differentiation trees: a
      linear programming approach.
AB  - MOTIVATION: Stem cell differentiation is largely guided by master transcriptional
      regulators, but it also depends on the expression of other types of genes, such
      as cell cycle genes, signaling genes, metabolic genes, trafficking genes, etc.
      Traditional approaches to understanding gene expression patterns across multiple
      conditions, such as principal components analysis or K-means clustering, can
      group cell types based on gene expression, but they do so without knowledge of
      the differentiation hierarchy. Hierarchical clustering can organize cell types
      into a tree, but in general this tree is different from the differentiation
      hierarchy itself. METHODS: Given the differentiation hierarchy and gene
      expression data at each node, we construct a weighted Euclidean distance metric
      such that the minimum spanning tree with respect to that metric is precisely the
      given differentiation hierarchy. We provide a set of linear constraints that are
      provably sufficient for the desired construction and a linear programming
      approach to identify sparse sets of weights, effectively identifying genes that
      are most relevant for discriminating different parts of the tree. RESULTS: We
      apply our method to microarray gene expression data describing 38 cell types in
      the hematopoiesis hierarchy, constructing a weighted Euclidean metric that uses
      just 175 genes. However, we find that there are many alternative sets of weights
      that satisfy the linear constraints. Thus, in the style of random-forest
      training, we also construct metrics based on random subsets of the genes and
      compare them to the metric of 175 genes. We then report on the selected genes and
      their biological functions. Our approach offers a new way to identify genes that
      may have important roles in stem cell differentiation. CONTACT: tperkins@ohri.ca
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 25847009
TI  - Tumoural Expression of Connective Tissue Growth Factor (CTGF) Impacts on Survival
      in Patients Diagnosed with Hepatocellular Carcinoma (HCC).
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) tends to develop in the liver when
      there is a high level of background inflammation (cirrhosis). Treatment options
      are limited and mainly based on systemic therapies such as anti-angiogenic drugs
      (e.g. sorafenib). Connective tissue growth factor (CTGF) is a matricellular
      protein involved in inflammation, tumour growth and angiogenesis. The aim of this
      study is to determine the expression of CTGF and hypoxia inducible factors (HIF)
      in HCC and to clarify its impact on relapse and survival. MATERIAL AND METHODS:
      Eligibility criteria for the study consisted of patients with a diagnosis of HCC,
      formalin-fixed and paraffin-embedded (FFPE) biopsy tissue, as well as relapse and
      available survival data. A tissue microarray was constructed from >= 70% tumoural
      sections. The expressions of CTGF, HIF1alpha and HIF2alpha were analysed by
      immunohistochemistry. The relationship between expression of CTGF/HIF1alpha and
      CTGF/HIF2alpha were analysed. Univariate and multivariate analyses were
      performed. RESULTS: Fifty-three patients were screened; 39 patients were eligible
      for this study. Patients were treated with radical intent. At the end of follow
      up, 59% patients relapsed (28.2% locally, 10.3% multicentric liver relapse and
      7.7% distant metastases). Estimated median disease-free survival (DFS) and
      overall survival (OS) were 23.4 (95%CI 7.18-39.66) and 38.6 months (95%CI 30.7
      46.6), respectively. Expression of CTGF was: negative 23.1%, focal 48.7% and
      diffuse 23.1%. A non-statistically significant relationship between expression of
      CTGF and HIF was shown supporting an alternative pathway for CTGF expression in
      HCC. In multivariate analysis CTGF expression was an independent factor related
      to OS, with shorter survival in those patients with focal/diffuse CTGF expression
      (HR 2.46; 95%CI 1.18-5.15). CONCLUSIONS: Our results support that expression of
      CTGF is an independent factor associated with shorter OS in HCC. Further analysis
      of CTGF expression in a larger series of HCC patients is required to confirm CTGF
      as a prognostic biomarker in HCC.

PMID- 25847010
TI  - Nanoradiopharmaceuticals for Bone Cancer Metastasis Imaging.
AB  - Drug delivery systems are under intense investigation all around the world,
      especially in oncology research. Indeed, in some cases, like bone metastasis,
      nanodrugs may represent the last and best choice for both treatment and imaging
      of early cancer foci. Nuclear medicine has been using MDP labelled with 99mTc as
      radiopharmaceuticals for many years; however, their use as
      nanoradiopharmaceuticals is very innovative and creates a new way to establish
      radiopharmacy in this new scenario offered by nanotechnology. In this study we
      developed and tested nano-MDP-labelled with 99mTc in rats induced with bone
      cancer metastasis and the results showed that it may work in patients. However,
      some further experiments are required in order to initiate protocols in humans. 

PMID- 25847011
TI  - Near-infrared Light Activatable Multimodal Gold Nanostructures Platform: An
      Emerging Paradigm for Cancer Therapy.
AB  - Traditional therapy for cancer is subject to some evident obstacles, including
      low effectiveness, resistance, systemic complication, etc. Gold nanostructures
      responsive to near-infrared (NIR) light are attractive for non-invasive and
      targeted therapy because of their unique physical properties especially strong
      absorption and scattering, and high surface area-to-volume ratio as well as the
      ease of which their surface chemistry can be manipulated to enhance
      biocompatibility surface modification and functionalization. In this Review, the
      progress of photothermal therapy (PTT) as well as the targeted delivery of
      anticancer agents as the predominant applications of gold nanostructures is
      detailed, with a focus on imaging-guided therapy and optimizing operational
      parameters. The NIR light-controlled targeted delivery and/or photothermal
      ablation of gold nanostructures in the treatment of metastasis are also briefly
      discussed. These gold nanostructures pave the way for developing better
      therapeutic strategies of cancer. 

PMID- 25847012
TI  - Acute ataxic neuropathy associated with hepatitis E virus infection.

PMID- 25847013
TI  - Reducing radiation in chronic total occlusion percutaneous coronary
      interventions.
AB  - The field of percutaneous intervention for chronic total occlusion (CTO) has
      enjoyed significant innovations in the recent years. Novel techniques and
      technologies have revolutionized the field and have resulted in considerably
      higher success rates even in patients with high anatomical complexity. Successful
      CTO recanalization is associated with significant clinical benefits, such as the
      improvement of angina and quality of life, reduced rates of surgical
      revascularization, improvement of left ventricular function and decreased
      mortality rates. However, complex CTO procedures often require prolonged x-ray
      exposure which have been associated with adverse long term outcomes. 

PMID- 25847014
TI  - Antagonism between MCL-1 and PUMA governs stem/progenitor cell survival during
      hematopoietic recovery from stress.
AB  - Understanding the critical factors that govern recovery of the hematopoietic
      system from stress, such as during anticancer therapy and bone marrow
      transplantation, is of clinical significance. We investigated the importance of
      the prosurvival proteins myeloid cell leukemia-1 (MCL-1) and B-cell lymphoma
      extra large (BCL-XL) in stem/progenitor cell survival and fitness during
      hematopoietic recovery from stress. Loss of a single Mcl-1 allele, which reduced
      MCL-1 protein levels, severely compromised hematopoietic recovery from
      myeloablative challenge and following bone marrow transplantation, whereas BCL-XL
      was dispensable in both contexts. We identified inhibition of proapoptotic p53
      upregulated modulator of apoptosis (PUMA) as the key role of MCL-1 in both
      settings, with Mcl-1(+/-);Puma(-/-) mice completely protected from the
      deleterious effects of loss of 1 Mcl-1 allele. These results reveal the molecular
      mechanisms that govern cell survival during hematopoietic recovery from stress. 

PMID- 25847015
TI  - T memory stem cells are the hierarchical apex of adult T-cell leukemia.
AB  - Adult T-cell leukemia (ATL) is a peripheral CD4(+) T-cell neoplasm caused by
      human T-cell leukemia virus type 1 (HTLV-1). Despite several investigations using
      human specimens and mice models, the exact origin of ATL cells remains unclear.
      Here we provide a new insight into the hierarchical architecture of ATL cells.
      HTLV-1-infected cells and dominant ATL clones are successfully traced back to
      CD45RA(+) T memory stem (TSCM) cells, which were recently identified as a unique
      population with stemlike properties, despite the fact that the majority of ATL
      cells are CD45RA(-)CD45RO(+) conventional memory T cells. TSCM cells from ATL
      patients are capable of both sustaining themselves in less proliferative mode and
      differentiating into other memory T-cell populations in the rapidly propagating
      phase. In a xenograft model, a low number of TSCM cells efficiently repopulate
      identical ATL clones and replenish downstream CD45RO(+) memory T cells, whereas
      other populations have no such capacities. Taken together, these findings
      demonstrate the phenotypic and functional heterogeneity and the hierarchy of ATL
      cells. TSCM cells are identified as the hierarchical apex capable of
      reconstituting identical ATL clones. Thus, this is the first report to
      demonstrate the association of a T-cell malignancy with TSCM cells. 

PMID- 25847016
TI  - Comparative efficacy of nimesulide and ketoprofen on inflammatory events in third
      molar surgery: a split-mouth, prospective, randomized, double-blind study.
AB  - This study aimed to compare the effect of nimesulide and ketoprofen on
      inflammatory parameters related to the surgical removal of third molars. A split
      mouth, prospective, randomized, double-blind study was conducted in patients
      undergoing removal of four third molars. Eighteen eligible patients were
      allocated to one of two groups to receive treatment two times a day with either
      ketoprofen 100 mg or nimesulide 100 mg for a period of 3 days. The rescue
      medication intake (number) and pain intensity were evaluated at 6, 12, 24, and 48
      h, and at 7 days postoperatively. Swelling and maximum mouth opening were
      evaluated at 24 h, 72 h, and 7 days postoperatively. The peak pain score occurred
      at 6h after surgery in the nimesulide group and at 12h in the ketoprofen group.
      There was no statistically significant difference between the groups, although
      pain relief was observed after 48 h in the nimesulide group and after 7 days in
      the ketoprofen group. For each group, there was a statically significant
      difference in pain scores among the studied periods (P<0.0001). None of the
      patients required rescue medication. There was a statistically significant
      difference in maximum mouth opening between the preoperative and postoperative
      periods (P<0.0001). Ketoprofen and nimesulide were effective at controlling pain,
      swelling, and trismus after the surgical removal of third molars.

PMID- 25847017
TI  - B-cell-activating factor belonging to the tumor necrosis factor family (BAFF) and
      a proliferation-inducing ligand (APRIL) levels in cerebrospinal fluid of patients
      with meningoencephalitis.
AB  - The B-cell-activating factor belonging to the tumor necrosis factor family (BAFF)
      and a proliferation-inducing ligand (APRIL) are important factors for the
      survival of transitional and mature B cells. High levels of BAFF and APRIL are
      present in adults with several autoimmune diseases. However, there are few
      reports about BAFF and APRIL levels in the cerebrospinal fluid (CSF) of patients
      with meningoencephalitis. We evaluated BAFF and APRIL levels in CSF samples from
      patients with viral meningitis (VM) (28 patients), autoimmune encephalitis (AE)
      associated with antineuronal antibodies (15 patients), idiopathic normal pressure
      hydrocephalus (iNPH) (11 patients), herpes simplex encephalitis (HSE) (9
      patients), bacterial meningitis (BM) (6 patients), and cryptococcal meningitis
      (CM) (4 patients). The CSF BAFF levels were significantly higher in patients with
      HSE, BM, or VM than AE or iNPH, and significantly higher in patients with CM than
      iNPH. The CSF APRIL levels were significantly higher in patients with HSE or BM
      than AE, VM, or iNPH. Although this is a preliminary report due to within-group
      variation and small sample size, the data suggest that CSF BAFF and APRIL levels
      are increased in HSE and BM, but not AE. 

PMID- 25847018
TI  - Case report: A Chinese child with Andersen-Tawil syndrome due to a de novo KCNJ2
      mutation.

PMID- 25847019
TI  - Fragile X premutation carriers: A systematic review of neuroimaging findings.
AB  - BACKGROUND: Expansion of the CGG repeat region of the FMR1 gene from less than 45
      repeats to between 55 and 200 repeats is known as the fragile X premutation.
      Carriers of the fragile X premutation may develop a neurodegenerative disease
      called fragile X-associated tremor/ataxia syndrome (FXTAS). Recent evidence
      suggests that premutation carriers experience other psychiatric difficulties
      throughout their lifespan. METHODS: Medline, EMBASE and PsychINFO were searched
      for all appropriate English language studies published between January 1990 and
      December 2013. 419 potentially relevant articles were identified and screened. 19
      articles were included in the analysis. RESULTS: We discuss key structural
      magnetic resonance imaging (MRI) findings such as the MCP sign and white matter
      atrophy. Additionally, we discuss how functional MRI results have progressed our
      knowledge of how FXTAS may manifest, including reduced brain activation during
      social and memory tasks in multiple regions. LIMITATIONS: This systematic review
      may have been limited by the search for articles on just 3 scientific databases.
      Differing techniques and methods of analyses between research groups and primary
      research articles may have caused differences in results between studies.
      CONCLUSION: Current MRI studies into the fragile X premutation have been
      important in the diagnosis of FXTAS and identifying potential pathophysiological
      mechanisms. Associations with blood based measures have also demonstrated that
      neurodevelopmental and neurodegenerative aspects of the fragile X premutation
      could be functionally and pathologically separate. Larger longitudinal studies
      will be required to investigate these conclusions.

PMID- 25847020
TI  - Acute ischemic strokes from small vessel vasculitis due to disseminated
      histoplasmosis infection.

PMID- 25847021
TI  - Use of failure mode, effect and criticality analysis to improve safety in the
      medication administration process.
AB  - RATIONALE, AIMS AND OBJECTIVES: To critically evaluate the causes of preventable
      adverse drug events during the nurse medication administration process in
      inpatient units with computerized prescription order entry and profiled automated
      dispensing cabinets in order to prioritize interventions that need to be
      implemented and to evaluate the impact of specific interventions on the
      criticality index. METHODS: This is a failure mode, effects and criticality
      analysis (FMECA) study. A multidisciplinary consensus committee composed of
      pharmacists, nurses and doctors evaluated the process of administering
      medications in a hospital setting in Spain. By analysing the process, all failure
      modes were identified and criticality was determined by rating severity,
      frequency and likelihood of failure detection on a scale of 1 to 10, using
      adapted versions of already published scales. Safety strategies were identified
      and prioritized. RESULTS: Through consensus, the committee identified eight
      processes and 40 failure modes, of which 20 were classified as high risk. The sum
      of the criticality indices was 5254. For the potential high-risk failure modes,
      21 different potential causes were found resulting in 24 recommendations.
      Thirteen recommendations were prioritized and developed over a 24-month period,
      reducing total criticality from 5254 to 3572 (a 32.0% reduction). The
      recommendations with a greater impact on criticality were the development of an
      electronic medication administration record (-582) and the standardization of
      intravenous drug compounding in the unit (-168). Other improvements, such as
      barcode medication administration technology (-1033), were scheduled for a longer
      period of time because of lower feasibility. CONCLUSION: FMECA is a useful
      approach that can improve the medication administration process.

PMID- 25847022
TI  - Serum pregnancy-associated plasma protein-A in the three trimesters of pregnancy:
      effects of maternal characteristics and medical history.
AB  - OBJECTIVE: To define the contribution of maternal variables which influence the
      measured level of maternal serum pregnancy-associated plasma protein-A (PAPP-A)
      in screening for pregnancy complications. METHODS: Maternal characteristics and
      medical history were recorded and serum PAPP-A was measured in women with a
      singleton pregnancy attending for three routine hospital visits at 11 + 0 to 13 +
      6, 19 + 0 to 24 + 6 and 30 + 0 to 34 + 6 weeks' gestation. For pregnancies
      delivering phenotypically normal live births or stillbirths >= 24 weeks'
      gestation, variables from maternal demographic characteristics and medical
      history that are important in the prediction of PAPP-A were determined from a
      linear mixed-effects multiple regression. RESULTS: Serum PAPP-A was measured in
      94,966 cases in the first trimester, 7785 in the second trimester and 8286 in the
      third trimester. Significant independent contributions to serum PAPP-A were
      provided by gestational age, maternal weight, height, racial origin, cigarette
      smoking, diabetes mellitus, method of conception, previous pregnancy with or
      without pre-eclampsia (PE) and birth-weight Z-score of the neonate in the
      previous pregnancy. The effects of some variables were similar and those for
      others differed in the three different trimesters. Random-effects multiple
      regression analysis was used to define the contribution of maternal variables
      that influence the measured level of serum PAPP-A and express the values as
      multiples of the median (MoMs). The model was shown to provide an adequate fit of
      MoM values for all covariates, both in pregnancies that developed PE and in those
      without this pregnancy complication. CONCLUSIONS: A model was fitted to express
      the measured serum PAPP-A across the three trimesters of pregnancy as MoMs, after
      adjusting for variables from maternal characteristics and medical history that
      affect this measurement.

PMID- 25847023
TI  - Distinctive oncological features of stage IIIA colorectal cancer: Analysis of
      prognostic factors for selective adjuvant chemotherapy.
AB  - INTRODUCTION: In the seventh TNM classification, stage IIIA includes tumors with
      early stage of bowel wall invasion and regional lymph node metastasis. We
      investigated the validity of the current TNM classification of patients with
      stage IIIA colorectal cancer and identified prognostic factors of them for
      ameliorating treatment strategies for them. METHODS: This study included the
      participation of four tertiary hospitals. A total of 4,236 patients with Stages I
      IIIB colorectal cancer were analyzed. The primary end point was the 5-year
      relapse-free survival. RESULTS: The 5-year relapse-free survival of patients with
      stage IIIA disease was similar to that of patients with stage IIA. The 5-year
      relapse-free survival was 88.9% in the chemotherapy group (n = 152) and 82.3% in
      the no-chemotherapy group (n = 36, P = 0.111). Tumor differentiation (moderate or
      poor) and venous invasion were independent prognostic factors of relapse-free
      survival. CONCLUSIONS: The relapse-free survival of patients with stage IIIA
      tumors was similar to that of patients with stage IIA tumors, and the prognosis
      of stage IIIA tumors varied significantly by the tumor factors identified. These
      factors can be used to predict the risk of disease recurrence and to optimize the
      use of adjuvant chemotherapy.

PMID- 25847024
TI  - Erythropoietin Promotes Neural Plasticity and Spatial Memory Recovery in Fimbria
      Fornix-Lesioned Rats.
AB  - BACKGROUND: Erythropoietin (EPO) upregulates the mitogen activated protein kinase
      (MAPK) cascade, a central signaling pathway in cellular plastic mechanisms, and
      is critical for normal brain development. OBJECTIVE: We hypothesized that EPO
      could modulate the plasticity mechanisms supporting spatial memory recovery in
      fimbria-fornix-transected animals. METHODS: Fimbria-fornix was transected in 3
      groups of rats. Seven days later, EPO was injected daily for 4 consecutive days
      within 10 minutes after training on a water maze task. RESULTS: Our results show
      that EPO injections 10 minutes after training produced a substantial spatial
      memory recovery in fimbria-fornix-lesioned animals. In contrast, an EPO injection
      shortly after fimbria-fornix lesion surgery does not promote spatial-memory
      recovery. Neither does daily EPO injection 5 hours after the water maze
      performance. EPO, on the other hand, induced the expression of plasticity-related
      genes like arc and bdnf, but this effect was independent of training or lesion.
      CONCLUSIONS: This finding supports our working hypothesis that EPO can modulate
      transient neuroplastic mechanisms triggered by training in lesioned animals.
      Consequently, we propose that EPO administration can be a useful trophic factor
      to promote neural restoration when given in combination with training.

PMID- 25847026
TI  - About three cases of ulceroglandular tularemia, is this the re-emergence of
      Francisella tularensis in Belgium?
AB  - Tularemia is a zoonosis caused by Francisella tularensis that can be transmitted
      by several ways to human being and cause different clinical manifestations. We
      report three clinical cases of tularemia with ulceroglandular presentation in
      young males acquired during outdoor activities in Southern Belgium. Confirmation
      of the diagnosis was established by serology. Only three cases of tularemia have
      been reported in Belgium between 1950 and 2012 by the National Reference
      Laboratory CODA-CERVA (Ref Lab CODA-CERVA) but re-emergence of tularemia is
      established in several European countries and F. tularensis is also well known to
      be present in animal reservoirs and vectors in Belgium. The diagnosis of
      tularemia has to be considered in case of suggestive clinical presentation
      associated with epidemiological risk factors. 

PMID- 25847025
TI  - Chemoradiation therapy for rectal cancer in the distal rectum followed by organ
      sparing transanal endoscopic microsurgery (CARTS study).
AB  - BACKGROUND: This prospective multicentre study was performed to quantify the
      number of patients with minimal residual disease (ypT0-1) after neoadjuvant
      chemoradiotherapy and transanal endoscopic microsurgery (TEM) for rectal cancer.
      METHODS: Patients with clinically staged T1-3 N0 distal rectal cancer were
      treated with long-course chemoradiotherapy. Clinical response was evaluated 6-8
      weeks later and TEM performed. Total mesorectal excision was advocated in
      patients with residual disease (ypT2 or more). RESULTS: The clinical stage was
      cT1 N0 in ten patients, cT2 N0 in 29 and cT3 N0 in 16 patients. Chemoradiotherapy
      related complications of at least grade 3 occurred in 23 of 55 patients, with two
      deaths from toxicity, and two patients did not have TEM or major surgery. Among
      47 patients who had TEM, ypT0-1 disease was found in 30, ypT0 N1 in one, ypT2 in
      15 and ypT3 in one. Local recurrence developed in three of the nine patients with
      ypT2 tumours who declined further surgery. Postoperative complications grade I
      IIIb occurred in 13 of 47 patients after TEM and in five of 12 after (completion)
      surgery. After a median follow-up of 17 months, four local recurrences had
      developed overall, three in patients with ypT2 and one with ypT1 disease.
      CONCLUSION: TEM after chemoradiotherapy enabled organ preservation in one-half of
      the patients with rectal cancer.

PMID- 25847027
TI  - Biomedical applications of trastuzumab: as a therapeutic agent and a targeting
      ligand.
AB  - Trastuzumab (TZ) is a humanized monoclonal antibody targeted to the extracellular
      domain of human epidermal growth factor receptor 2 (HER2), a tyrosine kinase
      receptor. TZ is approved by the Food and Drug Administration (FDA) for the
      treatment of HER2-overexpressing early stage and metastatic breast cancer and
      HER2-overexpressing metastatic gastric cancer. For breast cancer, it is
      recommended as both a single agent and in combination with standard chemotherapy.
      In the last few years, TZ has also been used as a targeting ligand.
      Overexpression of HER2 in breast cancer and the presence of free surface
      functional groups on TZ provide an opportunity to use it as a targeting ligand.
      TZ can be conjugated to various nanoparticulate systems such as dendrimers,
      polymeric, and protein nanoparticles to target drug delivery. TZ-conjugated
      inorganic nanoparticles have been reported for imaging and diagnostic purposes.
      This review summarizes the applications of TZ both as a therapeutic agent and as
      a targeting ligand. 

PMID- 25847028
TI  - Complete genome sequence of Haloarcula sp. CBA1115 isolated from non-purified
      solar salts.
AB  - Haloarcula sp. CBA1115, isolated from non-purified solar salts from South Korea,
      is a halophilic archaeon belonging to the family Halobacteriaceae. Here, we
      present the complete genome sequence of the strain Haloarcula sp. CBA1115
      (4,225,046bp, with a G+C content of 61.98%), which is distributed over one
      chromosome and five plasmids. A comparison of the genome sequence of Haloarcula
      sp. CBA1115 with those of members of its closely related taxa showed that the
      closest neighbor is Haloarcula hispanica Y27, a popular model organism for
      archaeal studies. The strain was found to possess a number of genes predicted to
      be involved in osmo-regulatory strategies and metal regulation, suggesting that
      it might be useful for bioremediation in extreme environments. 

PMID- 25847029
TI  - Discovery of germline-related genes in Cephalochordate amphioxus: A genome wide
      survey using genome annotation and transcriptome data.
AB  - The generation of germline cells is a critical process in the reproduction of
      multicellular organisms. Studies in animal models have identified a common
      repertoire of genes that play essential roles in primordial germ cell (PGC)
      formation. However, comparative studies also indicate that the timing and
      regulation of this core genetic program vary considerably in different animals,
      raising the intriguing questions regarding the evolution of PGC developmental
      mechanisms in metazoans. Cephalochordates (commonly called amphioxus or
      lancelets) represent one of the invertebrate chordate groups and can provide
      important information about the evolution of developmental mechanisms in the
      chordate lineage. In this study, we used genome and transcriptome data to
      identify germline-related genes in two distantly related cephalochordate species,
      Branchiostoma floridae and Asymmetron lucayanum. Branchiostoma and Asymmetron
      diverged more than 120 MYA, and the most conspicuous difference between them is
      their gonadal morphology. We used important germline developmental genes in
      several model animals to search the amphioxus genome and transcriptome dataset
      for conserved homologs. We also annotated the assembled transcriptome data using
      Gene Ontology (GO) terms to facilitate the discovery of putative genes associated
      with germ cell development and reproductive functions in amphioxus. We further
      confirmed the expression of 14 genes in developing oocytes or mature eggs using
      whole mount in situ hybridization, suggesting their potential functions in
      amphioxus germ cell development. The results of this global survey provide a
      useful resource for testing potential functions of candidate germline-related
      genes in cephalochordates and for investigating differences in gonad
      developmental mechanisms between Branchiostoma and Asymmetron species. 

PMID- 25847030
TI  - Microvesicles Derived From Human Mesenchymal Stem Cells Restore Alveolar Fluid
      Clearance in Human Lungs Rejected for Transplantation.
AB  - The need to increase the donor pool for lung transplantation is a major public
      health issue. We previously found that administration of mesenchymal stem cells
      "rehabilitated" marginal donor lungs rejected for transplantation using ex vivo
      lung perfusion. However, the use of stem cells has some inherent limitation such
      as the potential for tumor formation. In the current study, we hypothesized that
      microvesicles, small anuclear membrane fragments constitutively released from
      mesenchymal stem cells, may be a good alternative to using stem cells. Using our
      well established ex vivo lung perfusion model, microvesicles derived from human
      mesenchymal stem cells increased alveolar fluid clearance (i.e. ability to absorb
      pulmonary edema fluid) in a dose-dependent manner, decreased lung weight gain
      following perfusion and ventilation, and improved airway and hemodynamic
      parameters compared to perfusion alone. Microvesicles derived from normal human
      lung fibroblasts as a control had no effect. Co-administration of microvesicles
      with anti-CD44 antibody attenuated these effects, suggesting a key role of the
      CD44 receptor in the internalization of the microvesicles into the injured host
      cell and its effect. In summary, microvesicles derived from human mesenchymal
      stem cells were as effective as the parent mesenchymal stem cells in
      rehabilitating marginal donor human lungs. 

PMID- 25847048
TI  - INITIAT-E.D.: Impact of timing of INITIation of Antibiotic Therapy on mortality
      of patients presenting to an Emergency Department with sepsis.
AB  - OBJECTIVES: To analyse the association between time from triage to administration
      of initial antibiotics and mortality in all patients presenting with sepsis to a
      tertiary hospital ED. METHODS: A retrospective review of patients presenting to
      the ED with sepsis from January to December 2012 was conducted at Flinders
      Medical Centre, South Australia. Outcome measures were: time elapsed from triage
      to administration of initial antibiotic therapy and in-hospital mortality.
      RESULTS: A total of 220 patients presented with sepsis, comprising 102 cases of
      uncomplicated sepsis and 118 severe sepsis. The median time to antibiotic
      administration was 3.5 h (interquartile range [IQR] 1.7-6.6) and in-hospital
      mortality was 28.6% (95% CI 22.6-34.6%). There was no association observed
      between delays to antibiotics and mortality in the total patient population. When
      stratified by presenting severity, patients with severe sepsis demonstrated a
      trend towards increased mortality when delays to antibiotics exceeded 6 h from
      triage (HR = 2.25, 95% CI 0.91-5.59, P = 0.08) in comparison with <1 h.
      Significant delays to antibiotic administration occurred when initial agents were
      charted as a 'regular medicine' (9.4 h, IQR 5.1-16.6) in comparison with a 'once
      only order' (3.4 h, IQR 1.7-6.7), P < 0.001. CONCLUSIONS: Early administration of
      antibiotics specifically in patients with severe sepsis might be beneficial.
      Further studies within the ED are warranted to establish the effect of delayed
      antibiotics in a generalised sepsis cohort.

PMID- 25847031
TI  - Social context of preterm delivery in France in 2011 and impact on short-term
      health outcomes: the EPIPAGE 2 cohort study.
AB  - BACKGROUND: Low socio-economic context increases the risk of preterm delivery and
      may affect short-term outcomes in children born preterm. We described the social
      context of preterm delivery in France in 2011 and compared it with the general
      population of deliveries over the same period. We also studied how social context
      influenced pregnancy and delivery characteristics in the preterm population, and
      how it affected mortality and short-term morbidity in liveborn preterm children
      (<35 weeks). METHODS: We created an individual socio-economic vulnerability
      index, derived from multiple correspondence analysis based on maternal social
      information in the French National Perinatal Survey (NPS-2010). Weighted
      coordinates were applied to families from the EPIPAGE 2 study, a population-based
      cohort of preterm infants born in 2011, to quantify the infant's exposure to
      socio-economic vulnerability. Multivariable logistic models were used to relate
      the socio-economic context to pregnancy and delivery characteristics, and to
      assess its impact on short-term outcomes of the infants. RESULTS: Among mothers
      of preterm infants, gestational age decreased as socio-economic conditions
      worsened. In the most deprived group, women had more irregular pregnancy care, a
      higher prevalence of infection during pregnancy, and a lower rate of antenatal
      corticosteroid administration. The most deprived group was associated with a
      higher risk of severe morbidity for the preterm neonates. CONCLUSION: Our results
      emphasise the need for a large population-based surveillance system to identify
      the most deprived mothers, and to propose appropriate follow-up and care to these
      women and their infants in order to enhance long-term health.

PMID- 25847050
TI  - Hydroxyurea lowers transcranial Doppler flow velocities in children with sickle
      cell anaemia in a Nigerian cohort.
AB  - BACKGROUND: Sickle cell anaemia (SCA) is the leading genetic disorder in Nigeria.
      Elevated velocities >=170 cm/sec occur in about a third of Nigerian children with
      SCA. Chronic blood transfusion for stroke prevention is faced with a myriad of
      challenges in our practice. OBJECTIVES: To evaluate the effectiveness of
      hydroxyurea (HU) in reducing flow velocities in a cohort of Nigerian children
      with SCA and elevated velocities treated with HU. METHODS: An observational study
      was carried out on a cohort of Nigerian children with SCA and elevated velocities
      identified on routine transcranial Doppler (TCD) screening. HU was recommended in
      those with TCD velocities >= 170cm/sec as stipulated in our hospital protocol.
      Outcomes were compared after >=12 months of observation. RESULTS: Fifty children
      with elevated TCD velocities were studied; 31 consented to HU therapy and 19
      declined. Children on HU showed a statistically significant decline in mean
      velocities from 199.7 [17.1] cm/sec to 165.8 [20.7] cm/sec (P < 0.001) with a
      significant increase in mean packed cell volume from 21.1 [3.4] to 25.0 [2.8]%.
      Children without treatment had a significant rise in mean velocities from 190.2
      [10.8] cm/sec to 199.7 [14.9] cm/sec (P = 0.003). Children with conditional risk
      velocities on HU were less likely to convert to abnormal risk (P < 0.001). Two
      stroke events occurred, one in each group. No adverse effects of HU were recorded
      in the cohort. CONCLUSION: HU appears to significantly reduce TCD velocities in
      Nigerian children with SCA and elevated velocities >=170 cm/sec with beneficial
      effect on the haematological profile. HU may provide an effective approach to
      primary stroke prevention, particularly in Africa.

PMID- 25847051
TI  - Disclosing discourses: biomedical and hospitality discourses in patient education
      materials.
AB  - Patient education materials have the potential to strengthen the health literacy
      of patients. Previous studies indicate that readability and suitability may be
      improved. The aim of this study was to explore and analyze discourses inherent in
      patient education materials since analysis of discourses could illuminate values
      and norms inherent in them. Clinics in Sweden that provided colorectal cancer
      surgery allowed access to written information and 'welcome letters' sent to
      patients. The material was analysed by means of discourse analysis, embedded in
      Derrida's approach of deconstruction. The analysis revealed a biomedical
      discourse and a hospitality discourse. In the biomedical discourse, the subject
      position of the personnel was interpreted as the messenger of medical information
      while that of the patients as the carrier of diagnoses and recipients of
      biomedical information. In the hospitality discourse, the subject position of the
      personnel was interpreted as hosts who invite and welcome the patients as guests.
      The study highlights the need to eliminate paternalism and fosters a critical
      reflective stance among professionals regarding power and paternalism inherent in
      health care communication. 

PMID- 25847052
TI  - Knockdown of reticulon 4C by lentivirus inhibits human colorectal cancer cell
      growth.
AB  - Colorectal cancer is the third most common type of cancer worldwide with high
      cell motility and metastatic potential. Reticulon 4C (RTN4-C) is the shortest
      isoform of the reticulon family protein RTN4, which may act to induce cell
      apoptosis and suppress tumor development. The aim of the present study was to
      determine the role of RTN4-C in colorectal cancer, and potentially identify a
      novel target for anti-tumor therapy. To investigate the biological role of RTN4-C
      in colorectal cancer, the expression levels of RTN4-C were initially analyzed in
      six colorectal cancer cell lines by reverse transcription-quantitative polymerase
      chain reaction and western blot analysis. In addition, lentivirus-based RNA
      interference was utilized to knock down RTN4-C expression in RKO and DLD-1 cells
      with low and high levels of RTN4-C, respectively. The rate of proliferation
      decreased in RTN4-C silenced RKO and DLD-1 cells compared with the control, as
      determined using MTT and colony formation assays. Flow cytometric analysis
      revealed that RTN4-C knockdown in RKO cells led to cell cycle arrest at the G0/G1
      phase, particularly at the sub-G1 phase representing apoptotic cells. These
      results indicate that RTN4-C has an important role in colorectal cancer cell
      growth, which may provide a potential therapeutic approach for human colorectal
      cancer.

PMID- 25847053
TI  - First evidence of light-induced spin transition in molybdenum(IV).
AB  - Photo-induced spin transition in a molybdenum-zinc complex has been evidenced and
      fully characterized by Squid magnetometry and several spectroscopies performed
      under irradiation (IR, EPR, etc.). The phenomenon has been confirmed by X-ray
      diffraction and DFT calculations yielding a Light-Induced Excited Spin State
      Trapping Effect (LIESST) on a 4d transition metal ion. 

PMID- 25847054
TI  - Effects and Moderators of a Short Theory of Mind Intervention for Children with
      Autism Spectrum Disorder: A Randomized Controlled Trial.
AB  - Limited perspective taking or "Theory of Mind" (ToM) abilities are a core deficit
      of autism, and many interventions are aimed to improve ToM abilities. In this
      study, we investigated the effectiveness of a ToM treatment for children with
      autism spectrum disorders (ASD) and, for the first time, the moderating roles of
      social interaction style (SIS) and disruptive behavior (DB), to determine which
      children are most likely to respond to this intervention. The trial protocol is
      registered at www.trialregister.nl, trial number 2327 and published before the
      data collection was finished (www.trialsjournal.com). Children with autism aged 7
      12 years (n = 97) were randomized over a waitlist control or a treatment
      condition. Outcome measures included ToM and emotion understanding, parent and
      teacher questionnaires on children's social skills, ToM-related social behavior,
      and autistic traits. Six-month follow-up parent reported data were collected for
      the treatment group. The treatment had a positive effect on ToM understanding,
      parent-reported ToM behavior, and autistic traits, but not on parent or teacher
      reported social behavior. Passive SIS was associated with diminished treatment
      effects on autistic traits, but DB was unrelated to outcomes. The ToM
      intervention improved conceptual social understanding and ToM-related behavior of
      children with ASD. However, broader application of learned skills to other
      domains of functioning was limited. Individual differences with regard to
      treatment response are discussed.

PMID- 25847055
TI  - Tetrahymena Expresses More than a Hundred Proteins with Lipid-binding MORN Motifs
      that can Differ in their Subcellular Localisations.
AB  - Proteins with membrane occupation and recognition nexus (MORN) motifs are
      associated with cell fission in apicomplexan parasites, chloroplast division in
      Arabidopsis and the motility of sperm cells. We found that ciliates are among
      those that encode the largest variety of MORN proteins. Tetrahymena thermophila
      expresses 129 MORN protein-encoding genes, some of which are specifically up
      regulated during conjugation. A lipid-binding assay underpins the assumption that
      the predominant function of MORN motifs themselves is to confer the ability of
      lipid binding. The localisation of four MORN candidate proteins with similar
      characteristics highlights the functional diversity of this group especially in
      ciliates. 

PMID- 25847056
TI  - Sexual functioning and commitment to their current relationship among
      breastfeeding and regularly cycling women in Manila, Philippines.
AB  - This project investigates the relationship between lactation and female sexual
      functioning and relationship commitment among partnered women in urban Manila.
      Previous literature suggests that the time after giving birth is often rife with
      lower sexual functioning and relationship dissatisfaction. Given the important
      role of caregiving by multiple individuals in humans, the current cross-sectional
      study suggests that female sexuality may decline immediately after giving birth
      but then may increase afterwards. Non-cycling, breastfeeding (n = 86); cycling,
      breastfeeding (n = 48); and nulliparous, regularly cycling (n = 105) women were
      recruited from neighborhood health centers in Manila to complete questionnaires
      that assessed sexual functioning and relationship satisfaction, along with
      demographic variables. Cycling, breastfeeding women report the highest sexual
      functioning scores and commitment scores. Females undergoing life history trade
      offs between mating effort and parenting effort during the postpartum phase may
      employ a strategy in which they continue investment both in their offspring and
      in a romantic relationship. Variations in self-reported sexual functioning, level
      of commitment in a relationship, and love toward her current partner may indicate
      that breastfeeding women engage in sexual activities as part of a relationship
      maintenance strategy. Cultural and life history factors will serve as a framework
      for the findings. The current findings suggest women in Manila may experience a
      post-birth increase in sexual functioning that may be higher than pre-pregnancy
      levels. Future studies should incorporate a longitudinal component or a memory
      recall on pre-pregnancy and post-birth sexual functioning levels. 

PMID- 25847057
TI  - Comparing Methods to Denote Treatment Outcome in Clinical Research and
      Benchmarking Mental Health Care.
AB  - Approaches based on continuous indicators (the size of the pre-to-post-test
      change; effect size or DeltaT) and on categorical indicators (Percentage
      Improvement and the Jacobson-Truax approach to Clinical Significance) are
      evaluated to determine which has the best methodological and statistical
      characteristics, and optimal performance, in comparing outcomes of treatment
      providers. Performance is compared in two datasets from providers using the Brief
      Symptom Inventory or the Outcome Questionnaire. Concordance of methods and their
      suitability to rank providers is assessed. Outcome indicators tend to converge
      and lead to a similar ranking of institutes within each dataset. Statistically
      and conceptually, continuous outcome indicators are superior to categorical
      outcomes as change scores have more statistical power and allow for a ranking of
      providers at first glance. However, the Jacobson-Truax approach can complement
      the change score approach as it presents outcome information in a clinically
      meaningful manner. Copyright (c) 2015 John Wiley & Sons, Ltd. KEY PRACTITIONERS
      MESSAGES: When comparing various indicators or treatment outcome, statistical
      considerations designate continuous outcomes, such as the effect size of the pre
      post change (effect size or DeltaT) as the optimal choice. Expressing outcome in
      proportions of recovered, changed, unchanged or deteriorated patients has
      supplementary value, as it is more easily interpreted and appreciated by
      clinicians, managerial staff and, last but not the least, by patients. If
      categorical outcomes are used with small datasets, true differences in
      institutional performance may get obscured due to diminished power to detect
      differences. With sufficient data, outcome according to continuous and
      categorical indicators converge and lead to similar rankings of institutes'
      performance.

PMID- 25847058
TI  - Human lung microRNA profiling in pulmonary arterial hypertension secondary to
      congenital heart defect.
AB  - OBJECTIVE: Although several microRNAs were reported to play essential roles in
      pulmonary artery hypertension due to hypoxia or monocrotaline, their potential
      role in pulmonary arterial hypertension secondary to congenital heart disease is
      largely unknown. This study aimed to indentify microRNAs implicated in pulmonary
      arterial hypertension secondary to congenital heart disease in children. METHODS:
      Using microRNAs microarray, we profiled the microRNAs in the lung specimen from
      12 congenital heart disease patients, (6 with pulmonary arterial hypertension and
      the others without). We validated the microRNAs expression using RT-PCR
      experiments. Then, we predicted the target genes of the promising microRNAs by
      bioinformatical analysis and verified its regulating role by luciferase assay and
      western blot experiments. RESULTS: All the 12 patients were uneventfully
      recovered from cardiac surgery. Comparing to the non-pulmonary arterial
      hypertension lung tissue, 62 microRNAs were significantly up-regulated and 12
      were significantly de-regulated in the pulmonary arterial hypertension lung
      tissue. Among them 27 microRNAs reached P values <= 0.05, we validated the up
      regulation of microRNA-27b by RT-PCR experiments and found the expression level
      of microRNA-27b was correlated with preoperative mean pulmonary arterial
      pressure. In vitro, overexpression of microRNA-27b decreased the protein
      expression of NOTCH1 and significantly reduced luciferase activity. CONCLUSIONS:
      The current study revealed for the first time that microRNAs may be important
      regulators in pulmonary arterial hypertension secondary to congenital heart
      disease, and demonstrated the correlation between microRNA-27b and pulmonary
      arterial hypertension with the implication of NOTCH1.

PMID- 25847059
TI  - Diabetes self-management education is not associated with a reduction in long
      term diabetes complications: an effectiveness study in an elderly population.
AB  - RATIONALE, AIMS AND OBJECTIVES: The efficacy of diabetes self-management
      education on glycaemic control, self-care behaviour and knowledge has been
      established by short-term studies in experimental settings. The objective of this
      study was to assess its effectiveness to improve quality of care and reduce the
      risk of long-term diabetes complications in unselected older patients with
      recently diagnosed diabetes in routine clinical care. METHODS: Using population
      level health care administrative databases and registries, all patients aged >=66
      years in Ontario, Canada with diabetes for <5 years were identified. Self
      management education programme attendees (n = 8485) in 2006 were matched with non
      attendees using high-dimensional propensity scores, creating extremely well
      balanced study arms. Quality of care measures and the long-term risk of diabetes
      complications were compared. RESULTS: Self-management programme attendees were
      more likely than non-attendees to achieve process measures of quality of care
      such as retinal screening examinations (75.3% versus 70.3%, adjusted relative
      risk 1.05, 99% confidence interval 1.03-1.08), and >=2 glycated haemoglobin tests
      (57.5% versus 53.3%, adjusted relative risk 1.08, 99% confidence interval 1.05
      1.11). However, with a median follow-up of 5.3 years, diabetes complications and
      mortality were not different between arms. CONCLUSIONS: In real-world clinical
      care, self-management education for older patients with recently diagnosed
      diabetes was associated with modest improvements in quality of care, but no
      reductions in long-term clinical events.

PMID- 25847060
TI  - Disruption of cardiogenesis in human embryonic stem cells exposed to
      trichloroethylene.
AB  - Trichloroethylene (TCE) is ubiquitous in our living environment, and prenatal
      exposure to TCE is reported to cause congenital heart disease in humans. Although
      multiple studies have been performed using animal models, they have limited value
      in predicting effects on humans due to the unknown species-specific toxicological
      effects. To test whether exposure to low doses of TCE induces developmental
      toxicity in humans, we investigated the effect of TCE on human embryonic stem
      cells (hESCs) and cardiomyocytes (derived from the hESCs). In the current study,
      hESCs cardiac differentiation was achieved by using differentiation medium
      consisting of StemPro-34. We examined the effects of TCE on cell viability by
      cell growth assay and cardiac inhibition by analysis of spontaneously beating
      cluster. The expression levels of genes associated with cardiac differentiation
      and Ca2+ channel pathways were measured by immunofluorescence and qPCR. The
      overall data indicated the following: (1) significant cardiac inhibition, which
      was characterized by decreased beating clusters and beating rates, following
      treatment with low doses of TCE; (2) significant up-regulation of the
      Nkx2.5/Hand1 gene in cardiac progenitors and down regulation of the Mhc-7/cTnT
      gene in cardiac cells; and (3) significant interference with Ca2+ channel
      pathways in cardiomyocytes, which contributes to the adverse effect of TCE on
      cardiac differentiation during early embryo development. Our results confirmed
      the involvement of Ca2+ turnover network in TCE cardiotoxicity as reported in
      animal models, while the inhibition effect of TCE on the transition of cardiac
      progenitors to cardiomyocytes is unique to hESCs, indicating a species-specific
      effect of TCE on heart development. This study provides new insight into TCE
      biology in humans, which may help explain the development of congenital heart
      defects after TCE exposure. (c) 2015 Wiley Periodicals, Inc. Environ Toxicol 31:
      1372-1380, 2016.

PMID- 25847061
TI  - The stress of growing old: sex- and season-specific effects of age on allostatic
      load in wild grey mouse lemurs.
AB  - Chronic stress [i.e. long-term elevation of glucocorticoid (GC) levels] and aging
      have similar, negative effects on the functioning of an organism. Aged
      individuals' declining ability to regulate GC levels may therefore impair their
      ability to cope with stress, as found in humans. The coping of aged animals with
      long-term natural stressors is virtually unstudied, even though the ability to
      respond appropriately to stressors is likely integral to the reproduction and
      survival of wild animals. To assess the effect of age on coping with naturally
      fluctuating energetic demands, we measured stress hormone output via GC
      metabolites in faecal samples (fGCM) of wild grey mouse lemurs (Microcebus
      murinus) in different ecological seasons. Aged individuals were expected to
      exhibit elevated fGCM levels under energetically demanding conditions. In line
      with this prediction, we found a positive age effect in the dry season, when food
      and water availability are low and mating takes place, suggesting impaired coping
      of aged wild animals. The age effect was significantly stronger in females, the
      longer-lived sex. Body mass of males but not females correlated positively with
      fGCM in the dry season. Age or body mass did not influence fGCM significantly in
      the rainy season. The sex- and season-specific predictors of fGCM may reflect the
      differential investment of males and females into reproduction and longevity. A
      review of prior research indicates contradictory aging patterns in GC regulation
      across and even within species. The context of sampling may influence the
      likelihood of detecting senescent declines in GC functioning. 

PMID- 25847062
TI  - Toward predicting metastatic progression of melanoma based on gene expression
      data.
AB  - Primary and metastatic melanoma tumors share the same cell origin, making it
      challenging to identify genomic biomarkers that can differentiate them. Primary
      tumors themselves can be heterogeneous, reflecting ongoing genomic changes as
      they progress toward metastasizing. We developed a computational method to
      explore this heterogeneity and to predict metastatic progression of the primary
      tumors. We applied our method separately to gene expression and to microRNA
      (miRNA) expression data from ~450 primary and metastatic skin cutaneous melanoma
      (SKCM) samples from the Cancer Genome Atlas (TCGA). Metastatic progression scores
      from RNA-seq data were significantly associated with clinical staging of
      patients' lymph nodes, whereas scores from miRNA-seq data were significantly
      associated with Clark's level. The loss of expression of many characteristic
      epithelial lineage genes in primary SKCM tumor samples was highly correlated with
      predicted progression scores. We suggest that those genes/miRNAs might serve as
      putative biomarkers for SKCM metastatic progression. 

PMID- 25847063
TI  - Evaluation of the efficacy and safety of combinations of hydroquinone, glycolic
      acid, and hyaluronic acid in the treatment of melasma.
AB  - BACKGROUND: Various treatments are currently available for melasma. However,
      results are often disappointing. OBJECTIVES: 1 To assess the efficacy and safety
      of combinations of hydroquinone, glycolic acid, and hyaluronic acid in the
      treatment of melasma after topical application. 2 To evaluate the dermoscopy as a
      tool in diagnosis and follow-up of melasma treatment. PATIENTS AND METHODS: One
      hundred patients with mild, moderate-to-severe melasma were divided into five
      groups. Group I (twenty patients were treated with cream formula containing 4%
      hydroquinone), group II (twenty patients were treated with cream formula
      containing 4% hydroquinone + 10% glycolic acid), group III (twenty patients were
      treated with cream formula containing 4% hydroquinone + 0.01% hyaluronic acid),
      group IV (twenty patients were treated with cream formula containing 4%
      hydroquinone + 10% glycolic acid + 0.01% hyaluronic acid), and group V (twenty
      patients were treated with placebo cream). All patients were subjected to
      dermoscopic examination and digital photographs before and after treatment. The
      response and side effects were evaluated. RESULTS: Groups I, III, and IV showed
      highly significant changes in modified Melasma Area and Severity Index (mMASI)
      score after using the treatment. Group II showed significant change in mMASI
      score after using the treatment. The side effects were more reported in group II,
      followed by group IV, followed by group I, followed by group III. There was
      highly significant difference between the dermoscopic color findings before and
      after treatment. Vascularization was another dermoscopic finding. CONCLUSION: A
      cream formula containing 4% hydroquinone + 10% glycolic acid + 0.01% hyaluronic
      acid was very effective in treatment of melasma with tolerable side effects.
      Dermoscope is a valuable noninvasive tool in the diagnosis and follow-up of
      melasma treatment.

PMID- 25847064
TI  - The influence of teacher feedback on children's perceptions of student-teacher
      relationships.
AB  - BACKGROUND: Teachers can deliver feedback using person ('you are clever') or
      process terms ('you worked hard'). Person feedback can lead to negative academic
      outcomes, but there is little experimental research examining the impact of
      feedback on children's perceptions of the student-teacher relationship. AIM: We
      examined the effects of person, process, and no feedback on children's
      perceptions of their relationship with a (fictional) teacher following success
      and failure. SAMPLES: Participants were British children (145 aged 9-11 in
      experiment 1 and 98 aged 7-11 in experiment 2). METHOD: In experiment 1,
      participants read three scenarios where they succeeded and received one of two
      types of praise (person or process) or no praise. Participants then read two
      scenarios where they failed. In experiment 2, participants read that they had
      failed in three tasks and received one of two types of criticism (person or
      process) or no criticism. Participants then read two scenarios where they
      succeeded. They rated how much they liked the teacher and how much they felt that
      the teacher liked them. RESULTS: Children felt more positive about the student
      teacher relationship following success than failure. Type of praise did not
      influence perceptions of the student-teacher relationship following success or
      failure. However, person criticism led children to view the student-teacher
      relationship more negatively following failure and maintain this negative view
      following the first success. CONCLUSIONS: Success appears to be important for
      developing positive student-teacher relationships. In response to failure,
      teachers could avoid person criticism which may negatively influence the student
      teacher relationship.

PMID- 25847065
TI  - The camKK2/camKIV relay is an essential regulator of hepatic cancer.
AB  - Hepatic cancer is one of the most lethal cancers worldwide. Here, we report that
      the expression of Ca(2+) /calmodulin-dependent protein kinase kinase 2 (CaMKK2)
      is significantly up-regulated in hepatocellular carcinoma (HCC) and negatively
      correlated with HCC patient survival. The CaMKK2 protein is highly expressed in
      all eight hepatic cancer cell lines evaluated and is markedly up-regulated
      relative to normal primary hepatocytes. Loss of CaMKK2 function is sufficient to
      inhibit liver cancer cell growth, and the growth defect resulting from loss of
      CaMKK2 can be rescued by ectopic expression of wild-type CaMKK2 but not by kinase
      inactive mutants. Cellular ablation of CaMKK2 using RNA interference yields a
      gene signature that correlates with improvement in HCC patient survival, and
      ablation or pharmacological inhibition of CaMKK2 with STO-609 impairs
      tumorigenicity of liver cancer cells in vivo. Moreover, CaMKK2 expression is up
      regulated in a time-dependent manner in a carcinogen-induced HCC mouse model, and
      STO-609 treatment regresses hepatic tumor burden in this model. Mechanistically,
      CaMKK2 signals through Ca(2+) /calmodulin-dependent protein kinase 4 (CaMKIV) to
      control liver cancer cell growth. Further analysis revealed that CaMKK2 serves as
      a scaffold to assemble CaMKIV with key components of the mammalian target of
      rapamycin/ribosomal protein S6 kinase, 70 kDa, pathway and thereby stimulate
      protein synthesis through protein phosphorylation. CONCLUSION: The CaMKK2/CaMKIV
      relay is an upstream regulator of the oncogenic mammalian target of
      rapamycin/ribosomal protein S6 kinase, 70 kDa, pathway, and the importance of
      this CaMKK2/CaMKIV axis in HCC growth is confirmed by the potent growth
      inhibitory effects of genetically or pharmacologically decreasing CaMKK2
      activity; collectively, these findings suggest that CaMKK2 and CaMKIV may
      represent potential targets for hepatic cancer.

PMID- 25847067
TI  - Catecholaminergic contributions to vocal communication signals.
AB  - Social context affects behavioral displays across a variety of species. For
      example, social context acutely influences the acoustic and temporal structure of
      vocal communication signals such as speech and birdsong. Despite the prevalence
      and importance of such social influences, little is known about the neural
      mechanisms underlying the social modulation of communication. Catecholamines are
      implicated in the regulation of social behavior and motor control, but the degree
      to which catecholamines influence vocal communication signals remains largely
      unknown. Using a songbird, the Bengalese finch, we examined the extent to which
      the social context in which song is produced affected immediate early gene
      expression (EGR-1) in catecholamine-synthesising neurons in the midbrain.
      Further, we assessed the degree to which administration of amphetamine, which
      increases catecholamine concentrations in the brain, mimicked the effect of
      social context on vocal signals. We found that significantly more
      catecholaminergic neurons in the ventral tegmental area and substantia nigra (but
      not the central grey, locus coeruleus or subcoeruleus) expressed EGR-1 in birds
      that were exposed to females and produced courtship song than in birds that
      produced non-courtship song in isolation. Furthermore, we found that amphetamine
      administration mimicked the effects of social context and caused many aspects of
      non-courtship song to resemble courtship song. Specifically, amphetamine
      increased the stereotypy of syllable structure and sequencing, the repetition of
      vocal elements and the degree of sequence completions. Taken together, these data
      highlight the conserved role of catecholamines in vocal communication across
      species, including songbirds and humans. 

PMID- 25847066
TI  - Effect of beta-anhydroicaritin on the expression levels of tumor necrosis factor
      alpha and matrix metalloproteinase-3 in periodontal tissue of diabetic rats.
AB  - The present study aimed to investigate the effect of beta-anhydroicaritin on the
      expression levels of tumor necrosis factor (TNF)-alpha and matrix
      metalloproteinase (MMP)-3, and the pathological changes in the periodontal tissue
      of diabetic rats. Male Wistar rats (n=40; three months old) were randomly divided
      into four groups: Normal control group, diabetes group, diabetes + beta
      anhydroicaritin group and diabetes + urate group, (n=10 in each group). Following
      an overnight fast, diabetes was induced by intraperitoneal injection of
      streptozocin. The rats were maintained for 12 weeks and the blood sugar, urine
      sugar and body weight were assessed in week 12. Histological changes of the
      periodontal tissues were observed by hematoxylin and eosin staining, and the
      expression levels of TNF-alpha and MMP-3 were observed by immunohistochemistry.
      Following 12 weeks, the TNF-alpha grey value in the diabetes group was
      significantly lower compared with that in the control group (P<0.05), while no
      significant difference was observed between TNF-alpha levels in the diabetes +
      beta-anhydroicaritin group, diabetes + urate group and the control group
      (P>0.05). However, TNF-alpha levels in the diabetes + beta-anhdroicaritin group
      and diabetes + urate group were significantly higher compared with those in the
      diabetes group (P<0.05), and those in the diabetes + beta-anhydroicaritin group
      were lower compared with those in the diabetes + urate group (P<0.05). The MMP-3
      grey value in the diabetes group was significantly lower compared with that in
      the control group (P<0.05), while no significant difference was observed between
      MMP-3 levels in the diabetes + beta-anhydroicaritin group, diabetes + urate group
      and the control group (P>0.05). However, MMP-3 levels the diabetes + beta
      anhydroicaritin group and diabetes + urate group were significantly higher
      compared with those in the diabetes group (P<0.05), and those in the diabetes +
      beta-anhydroicaritin group were lower compared with those in the diabetes + urate
      group (P<0.01). beta-anhydroicaritin normalized the expression levels of TNF
      alpha and MMP-3 in the periodontal tissue of diabetic rats and led to the
      recovery of the changes in the morphological structure of the periodontal tissue.

PMID- 25847068
TI  - Occurrence of periodontal pathogens in ethnic groups from a native Brazilian
      reservation.
AB  - OBJECTIVE: The present study was designed to evaluate the occurrence of
      periodontal pathogens in the subgingival biofilm of 100 native Brazilians living
      at the Umutina Indian Reservation, Mato Grosso State, Brazil. METHODS:
      Periodontal clinical examinations were carried out prior to collection of
      subgingival biofilm, and the presence of 14 periodontal microorganisms was
      evaluated by polymerase chain reaction (PCR). The prevalence and risk analysis
      was performed using Cochran and Mantel-Haenszel statistics for dichotomous
      variables or Pearson's chi-squared test for analysis of proportions when
      variables had three or more categories. The interrelations between clinical and
      microbiological parameters were assessed using Fisher's exact test and the Mann
      Whitney U test. RESULTS: Individuals with chronic periodontitis were frequently
      colonized by the association between Porphyromonas gingivalis and Campylobacter
      rectus, P. gingivalis and Prevotella intermedia, or P. gingivalis and Tannerella
      forsythia. Patients with chronic periodontitis were also colonized by
      Porphyromonas gulae and P. intermedia or by the association between P. gulae and
      T. forsythia. P. gulae was detected only in the subgingival samples from natives
      on a traditional diet. Gingival bleeding was associated with Aggregatibacter
      actinomycetemcomitans, Fusobacterium nucleatum, T. forsythia, P. gingivalis, P.
      gulae, Porphyromonas endodontalis, P. intermedia, and Prevotella nigrescens.
      Treponema denticola was uncommon. CONCLUSIONS: Peculiar microbiota was
      demonstrated to be associated with different periodontal disease statuses in
      native Brazilians, with modest occurrence of certain pathogens, such as T.
      denticola, and the presence of P. gulae in natives with gingivitis or chronic
      periodontitis.

PMID- 25847070
TI  - Balo-like lesion associated with psoriasis and chronic autoimmune thyroiditis.

PMID- 25847069
TI  - Effects of aging on evoked retrusive tongue actions.
AB  - OBJECTIVE: Tongue strength, timing, and coordination deficits may underlie age
      related swallowing function. Retrusive tongue actions are likely important in
      retrograde bolus transport. However, age-related changes in retrusive tongue
      muscle contractile properties have not been identified in animal studies. Because
      previous studies employed whole hypoglossal nerve stimulation that activated both
      protrusive and retrusive tongue muscles, co-contraction may have masked retrusive
      muscle force decrements. The hypotheses of this study were: (1) retrusive tongue
      muscle contraction forces would be diminished and temporal characteristics
      prolonged in old rats when lateral nerves were selectively activated, and (2)
      greater muscle contractile forces with selective lateral branch stimulation would
      be found relative to whole hypoglossal nerve stimulation. DESIGN: Nineteen
      Fischer 344/Brown Norway rats (9 old, 10 young adult) underwent tongue muscle
      contractile property recording elicited by: (1) bilateral whole hypoglossal nerve
      stimulation, and (2) selective lateral branch stimulation. Twitch contraction
      time (CT), half-decay time, maximal twitch and tetanic forces, and a fatigue
      index were measured. RESULTS: For whole nerve stimulation, CT was significantly
      longer in the old group. No significant age group differences were found with
      selective lateral nerve stimulation. Significantly reduced twitch forces (old
      group only), increased tetanic forces and significantly less fatigue were found
      with selective lateral nerve stimulation than with whole hypoglossal stimulation.
      CONCLUSIONS: Retrusive tongue forces are not impaired in old rats. Deficits
      observed in swallowing with aging may be due to other factors such as inadequate
      bolus propulsive forces, mediated by protrusive tongue muscles, or
      timing/coordination of muscle actions.

PMID- 25847071
TI  - Short Stature Screening by Accurate Length Measurement in Infants with a Birth
      Weight <9th Centile.
AB  - BACKGROUND/AIMS: Intrauterine growth restriction is an indication for growth
      hormone treatment. Birth length (BL) is needed to evaluate the influence of birth
      size on childhood short stature. However, BL is commonly measured only
      approximately, if at all. A single-centre study was undertaken to determine the
      value of measuring accurate and targeted BL and parental height (PH) for neonates
      with a birth weight (BW) <=9th centile, identifying short [BL <=-2 standard
      deviation scores (SDS)] and light newborns (BW <=-2 SDS), and remeasuring short
      neonates at 2 years in order to detect those not showing catch-up growth.
      METHODS: Information was collected on all live births (n = 3,798) in a single
      maternity unit during a 1-year period. RESULTS: BW was <=9th centile in 481
      neonates (12.7%) of whom 47 were light but not short, 46 were short, and 60 were
      both light and short. Of 107 eligible infants, 57 (53%) attended the 2-year
      follow-up; failure of catch-up growth was identified in 6 infants (11%) of whom
      only 1 was already known to medical services. PH was measured in both parents of
      52/153 (34%) light and/or short infants. CONCLUSION: Targeted and accurate BL
      measurement in newborns with a BW <=9th centile is a promising alternative to the
      current practices. The feasibility of PH measurement after birth still requires
      further evaluation. (c) 2015 S. Karger AG, Basel.

PMID- 25847074
TI  - Effect of Filling Type and Heating Method on Prevalence of Listeria species and
      Listeria monocytogenes in Dumplings Produced in Poland.
AB  - The count of Listeria monocytogenes was determined, before and after heat
      treatment, in 200 samples of dumplings of 9 brands and with different types of
      stuffing. Analyses were conducted according to ISO 11290-1 standard and with real
      time PCR method. The highest count of L. monocytogenes was found in meat
      dumplings (10(2) to 10(4) CFU/g), whereas products with white cheese-potato
      stuffing and vegetable-mushroom stuffing contained significantly less Listeria,
      20 to 80 and 5 to 32 CFU/g, respectively. In cooled meat dumplings the extent of
      contamination depended significantly on the producer. In addition, a significant
      (P < 0.05) correlation was determined between contamination level and meat
      content in the stuffing (rho = 0.418), especially in stuffing containing pork
      meat (0.464), contrary to beef-containing stuffing (0.284). Heating dumplings in
      boiling water for 2 min completely eliminated L. monocytogenes in meat dumplings.
      In contrast, the microwave heating applied for 2 min at 600 W only reduced the
      count of L. monocytogenes by 1 to 2 logs. Hence, the microwave heating failed to
      reduce the risk of infection with this pathogen below the level permissible in
      the EU regulation, especially in the most contaminated samples. In this case, the
      efficacy of microwave heating was significantly (P < 0.05) affected by the
      initial count of L. monocytogenes (rho = 0.626), then by meat content in the
      stuffing (0.476), and to the lowest extent--by the type of meat (0.415 to 0.425).
      However, no Listeria sp. and L. monocytogenes were isolated from cooked dumplings
      with fruits (strawberries or blueberries).

PMID- 25847072
TI  - Roles of the lateral fenestration residues of the P2X4 receptor that contribute
      to the channel function and the deactivation effect of ivermectin.
AB  - P2X receptors are cation-permeable ion channels gated by extracellular adenosine
      triphosphate (ATP). Available crystallographic data suggest that ATP-binding
      ectodomain is connected to the transmembrane pore domain by three structurally
      conserved linker regions, which additionally frame the lateral fenestrations
      through which permeating ions enter the channel pore. The role of these linker
      regions in relaying the conformational change evoked by ATP binding of the
      ectodomain to the pore-forming transmembrane domain has not been investigated
      systematically. Using P2X4R as our model, we employed alanine and serine
      replacement mutagenesis to determine how the side chain structure of these linker
      regions influences gating. The mutants Y54A/S, F198A/S, and W259A/S all
      trafficked normally to the plasma membrane of transfected HEK293 cells but were
      poorly responsive to ATP. Nevertheless, the function of the F198A/S mutants could
      be recovered by pretreatment with the known positive allosteric modulator of
      P2X4R, ivermectin (IVM), although the IVM sensitivity of this mutant was
      significantly impaired relative to wild type. The functional mutants Y195A/S,
      F200A/S, and F330A/S exhibited ATP sensitivities identical to wild type,
      consistent with these side chains playing no role in ATP binding. However,
      Y195A/S, F200A/S, and F330A/S all displayed markedly changed sensitivity to the
      specific effects of IVM on current deactivation, suggesting that these positions
      influence allosteric modulation of gating. Taken together, our data indicate that
      conserved amino acids within the regions linking the ectodomain with the pore
      forming transmembrane domain meaningfully contribute to signal transduction and
      channel gating in P2X receptors. 

PMID- 25847073
TI  - The vesicular nucleotide transporter (VNUT) is involved in the extracellular ATP
      effect on neuronal differentiation.
AB  - Before being released, nucleotides are stored in secretory vesicles through the
      vesicular nucleotide transporter (VNUT). Once released, extracellular ATP
      participates in neuronal differentiation processes. Thus, the expression of a
      functional VNUT could be an additional component of the purinergic system which
      regulates neuronal differentiation and axonal elongation. In vitro expression of
      VNUT decreases neuritogenesis in N2a cells differentiated by retinoic acid
      treatment, whereas silencing of VNUT expression increases the number and length
      of neurites in these cells. These results highlight the role of VNUT in the
      neuritogenic process because this transporter regulates the ATP content in
      neurosecretory vesicles. 

PMID- 25847075
TI  - Vemurafenib/dabrafenib and trametinib.

PMID- 25847076
TI  - Education and evaluation for the development of a qualified psychiatrist: Report
      of the Teachers of Psychiatry meeting - Shanghai.

PMID- 25847077
TI  - Effects on Physical Health of a Multicomponent Programme for Overweight and
      Obesity for Adults with Intellectual Disabilities.
AB  - BACKGROUND: Overweight and obesity are major health risk factors in people with
      intellectual disabilities. The aim of this study was to test the effectiveness of
      a multicomponent programme (physical activity, diet and motivation) for
      overweight and obesity in adults with intellectual disabilities. MATERIAL AND
      METHODS: A quasi-experimental design with repeated-measures and non-equivalent
      control group (n = 33, n = 31) was used. The programme was conducted over 17
      weeks, with follow-up at 6 months in a sample of Spanish adults with a mild and
      moderate intellectual disability from a community occupational day centre, aged
      from 23 to 50, 40.6% of which were women. RESULTS: A significant reduction in
      weight and diastolic blood pressure was obtained over time, and this reduction
      was maintained in the follow-up for weight. Reduction in heart rate was only
      marginally significant. CONCLUSIONS: The treatment was effective in reducing
      overweight and obesity, improving cardiovascular capacity and therefore the
      physical health of the participants.

PMID- 25847078
TI  - Sociodemographic characteristics and attitudes towards motherhood among single
      women compared with cohabiting women treated with donor semen - a Danish
      multicenter study.
AB  - OBJECTIVE: To examine sociodemographic characteristics, family backgrounds,
      reproductive histories, and attitudes towards motherhood in single vs. cohabiting
      women seeking treatment with donor semen. DESIGN: Baseline data collection in a
      multicenter cohort study. SETTING: All nine public fertility clinics in Denmark.
      SAMPLE: In total n = 311 childless women initiating assisted reproduction using
      donor semen. METHODS: Self-reported questionnaire responses from n = 184 single
      women seeking treatment by using donor semen were compared with responses from n
      = 127 cohabiting women. MAIN OUTCOME MEASURES: Sociodemographic characteristics,
      family backgrounds, reproductive histories, attitudes towards motherhood.
      RESULTS: Single women were 3.5 years older on average when initiating treatment
      compared with cohabiting women. No significant differences were found regarding
      sociodemographic characteristics, previous long-term relationships, previous
      pregnancies, or attitudes towards motherhood between single women and cohabiting
      women. The vast majority of single women wanted to achieve parenthood with a
      partner, 85.8% wished to have a partner in the future, and approximately half of
      them preferred for a partner to take parental responsibilities. CONCLUSIONS: In
      this study single women seeking treatment with donor semen in the public health
      system did not differ from cohabiting women, except that they were older. To be a
      single mother by choice is not their preferred way of parenthood, but a solution
      they needed to accept.

PMID- 25847079
TI  - P,O-Phosphinophenolate zinc(II) species: synthesis, structure and use in the ring
      opening polymerization (ROP) of lactide, epsilon-caprolactone and trimethylene
      carbonate.
AB  - The P,O-type phosphinophenol proligands (1.H, 2-PPh2-4-Me-6-Me-C6H2OH; 2.H, 2
      PPh2-4-Me-6-(t)Bu-C6H2OH) readily react with one equiv. of ZnEt2 to afford in
      high yields the corresponding Zn(II)-ethyl dimers of the type [(kappa(2)-P,O)Zn
      Et]2 (3 and 4) with two MU-OPh bridging oxygens connecting the two Zn(II)
      centers, as determined by X-ray diffraction (XRD) studies in the case of 3. Based
      on diffusion-ordered NMR spectroscopy (DOSY), both species 3 and 4 retain their
      dimeric structures in solution. The alcoholysis reaction of Zn(II) alkyls 3 and 4
      with BnOH led to the high yield formation of the corresponding Zn(II) benzyloxide
      species [(kappa(2)-P,O)Zn-OBn]2 (5 and 6), isolated in a pure form as colorless
      solids. The centrosymmetric and dimeric nature of Zn(II) alkoxides 5 and 6 in
      solution was deduced from DOSY NMR experiments and multinuclear NMR data. Though
      the heteroleptic species 5 is stable in solution, its analogue 6 is instable in
      CH2Cl2 solution at room temperature to slowly decompose to the corresponding
      homoleptic species 8via the transient formation of (kappa(2)-P,O)2Zn2(MU-OBn)(MU
      kappa(1):kappa(1)-P,O) (6'). Crystallization of compound 6 led to crystals of 6',
      as established by XRD analysis. The reaction of ZnEt2 with two equiv. of 1.H and
      2.H allowed access to the corresponding homoleptic species of the type [Zn(P,O)2]
      (7 and 8). All gathered data are consistent with compound 7 being a dinuclear
      species in the solid state and in solution. Data for species 8, which bears a
      sterically demanding P,O-ligand, are consistent with a mononuclear species in
      solution. The Zn(II) alkoxide species 5 and the [Zn(P,O)2]-type compounds 7 and 8
      were evaluated as initiators of the ring-opening polymerization (ROP) of lactide
      (LA), epsilon-caprolactone (epsilon-CL) and trimethylene carbonate (TMC). Species
      5 is a well-behaved ROP initiator for the homo-, co- and ter-polymerization of
      all three monomers with the production of narrow disperse materials under living
      and immortal conditions. Though species 7 and 8 are ROP inactive on their own,
      they readily polymerize LA in the presence of a nucleophile such as BnOH to
      produce narrow disperse PLA, presumably via an activated-monomer ROP mechanism.

PMID- 25847080
TI  - miR-204-5p promotes the adipogenic differentiation of human adipose-derived
      mesenchymal stem cells by modulating DVL3 expression and suppressing Wnt/beta
      catenin signaling.
AB  - MicroRNAs (miRNAs or miRs) play an important regulatory role during adipogenesis,
      and have been studied extensively in this regard. Specifically, the switch
      between the differentiation of mesenchymal stem cells (MSCs) towards adipogenic
      vs. osteogenic lineages is regulated by miR-204 which controls the expression of
      Runx2. However, the association between miR-204-5p and the Wnt/beta-catenin
      signaling pathway during adipogenesis has not yet been clarified. In the present
      study, we demonstrate that miR-204-5p regulates the in vitro adipogenesis of
      human adipose-derived mesenchymal stem cells (hADSCs). The level of miR-204-5p
      was shown to be gradually upregulated during adipocytic differentiation, together
      with the mRNA expression of the critical adipogenic transcription factors,
      cytidine-cytidine-adenosine-adenosine-thymidine (CCAAT) enhancer binding protein
      alpha (C/EBPalpha) and peroxisome proliferator-activated receptor gamma
      (PPARgamma), and the mature adipogenic marker, fatty acid binding protein 4
      (FABP4). We further demonstrate that while the overexpression of miR-204-5p
      promotes adipogenesis, its knockdown causes the inhibition of this process. We
      then used bioinformatics tools and luciferase reporter assay to establish that
      dishevelled segment polarity protein 3 (DVL3), a key regulator of the Wnt/beta
      catenin signaling pathway, is a direct target of miR-204-5p. In addition, the
      overexpression of DVL3 led to an increase in beta-catenin and cyclin D1 (CCND1)
      expression and, by contrast, the knockdown of DVL3 led to a decrease in the
      expression of beta-catenin and CCND1. The knockdown of DVL3 significantly
      promoted adipogenesis. Finally, we demonstrated that the overexpression of miR
      204-5p induced the downregulation of beta-catenin and the canonical Wnt target
      gene, CCND1, in mature adipoctyes, while its knockdown led to their upregulation.
      Taken together, our data suggest that miR-204-5p regulates adipogenesis by
      controlling DVL3 expression and subsequently inhibiting the activation of the
      Wnt/beta-catenin signaling pathway.

PMID- 25847081
TI  - Pharmacokinetics of intra-articular betamethasone sodium phosphate and
      betamethasone acetate and endogenous hydrocortisone suppression in exercising
      horses.
AB  - To the date, no reports exist of the pharmacokinetics (PK) of betamethasone (BTM)
      sodium phosphate and betamethasone acetate administered intra-articular (IA) into
      multiple joints in exercising horses. The purpose of the study was to determine
      the PK of BTM and HYD concentrations in plasma and urine after IA administration
      of a total of 30 mg BTM. Eight 4 years old Thoroughbred mares were exercised on a
      treadmill and BTM was administered IA. Plasma and urine BTM and HYD were
      determined via high performance liquid chromatography spectrometry for 6 weeks.
      Concentration-time profiles of BTM and HYD in plasma and urine were used to
      generate PK estimates for non-compartmental analyses and comparisons among times
      and HYD concentrations. BTM in plasma had greater Tmax (Tmax 0.8 h) vs. urine
      (Tmax 7.1 h). Urine BTM concentration (ng/mL) and amount (AUClast ; h * ng/mL)
      were greater than plasma. HYD was suppressed for at least 3 days (<1 ng/mL) for
      all horses. The time of last quantifiable concentration of BTM (Tlast ; hour) was
      not significantly different in plasma than urine. Use of highly sensitive HPLC
      MS/MS assays enabled early detection and prolonged and consistent determination
      of BTM in plasma and urine.

PMID- 25847082
TI  - Effect of persistent and transient hypothyroidism on histoarchitecture and
      antioxidant defence system in rat brain.
AB  - The present study reports the effect of 6-n-propylthiouracil (PTU)-induced
      hypothyroidism on oxidative stress parameter, lipid peroxidation (LPx) and major
      antioxidant enzyme expressions such as superoxide dismutase (SOD: SOD1 and SOD2)
      and catalase (CAT) in cerebral cortex rat brain during postnatal persistent (90
      days PTU treatment from birth) and transient (30 days PTU treatment from birth
      followed by PTU withdrawal for 60 days) hypothyroidism. Enhanced level of LPx was
      observed in transient hypothyroid rats with respect to control and persistent
      hypothyroid rats. Significantly increased activity of SOD and expression of SOD1
      were observed in cerebral cortex of both persistent and transient hypothyroid
      rats as compared to control. However, unaltered translated level of SOD2 was
      observed among the groups. Activity of CAT was increased in transient hypothyroid
      rats, whereas translate level of CAT was increased in both the regions of
      persistent as well as transient hypothyroidism. The histoarchitecture of cerebral
      cortex clearly showed a decline in neuronal migration with neurons packed
      together in both persistent and transient hypothyroid rats as compared to
      control. These results suggest that deprivation of thyroid hormone modulates
      redox status and causes oxidative stress in rat brain cerebral cortex during
      postnatal development and maturation.

PMID- 25847083
TI  - STIMA: a short screening test for ideo-motor apraxia, selective for action
      meaning and bodily district.
AB  - We propose STIMA, a short test for ideo-motor apraxia, allowing us to quantify
      the apraxic deficit according to action meaning and affected body segment. STIMA
      is based on a neurocognitive model holding that there are two processes involved
      in action imitation (i.e., a semantic route for recognizing and imitating known
      gestures, and a direct route for reproducing new gestures). The test allows to
      identify which imitative process has been selectively impaired by brain damage
      (direct vs. semantic route) and possible deficits depending on the body segment
      involved (hand/limb vs. hand/fingers). N = 111 healthy participants were
      administered with an imitation task in two separated blocks of known and new
      gestures. In each block, half of the gestures were performed mainly with the
      proximal part of the upper limb and the remaining half with the distal one. It
      resulted in 18 known gestures (nine proximal and nine distal) and 18 new gestures
      (nine proximal and nine distal) for a total of 36. Each gesture was presented up
      to a maximum of two times. Detailed criteria are used to assign the final
      imitation score. Cut offs, equivalent scores and main percentile scores were
      computed for each subscale. Participants imitated better known than new gestures,
      and proximal better than distal gestures. Age influenced performance on all
      subscales, while education only affected one subscale. STIMA is easy and quick to
      administer, and compared to previous tests, it offers important information for
      planning adequate rehabilitation programs based on the functional locus of the
      deficit.

PMID- 25847084
TI  - Gender-specific effects of CGP 55845, GABAB receptor antagonist, on neuromuscular
      coordination, learning and memory formation in albino mouse following neonatal
      hypoxia-ischemia insult.
AB  - GABAB receptor antagonists are experimentally proved as spatial memory enhancers
      in mouse models but their role has not been described following hypoxic-ischemic
      insult. 10-day-old albino mice were subjected to Murine model of hypoxia and
      ischemia. Following brain damage, mice were fed on normal rodent diet till they
      were 13 weeks old. At this time point, mice were divided into two groups. Group 1
      received saline and group 2 received intraperitoneally CGP 55845 (1 mg/ml
      solvent/Kg body weight) for 12 days. Behavioural observations were made during
      rota rod, open field and Morris water maze test along with brain infarct
      measurement in both CGP 55845 treated and untreated groups. It was observed that
      application of GABAB receptor antagonist improved the over all motor function in
      male and female albino mice but effects were more pronounced in males. In open
      field, CGP 55845-treated female mice showed poor performance. CGP 55845 had no
      significant effect on learning and memory formation during Morris water maze test
      and also on brain infract size in both genders following hypoxia ischemia
      encephalopathy. Effects of CGP 55845 can be further explored in a dose and
      duration dependent manner to improve the learning and memory in albino mice
      following neonatal brain damage.

PMID- 25847085
TI  - An epidemiologic study of restless legs syndrome among Chinese children and
      adolescents.
AB  - To determine the prevalence of restless legs syndrome (RLS) in Chinese children
      and adolescents as well as the impact of the disorder on 8-11 and 12-17 years
      old. This population-based study was conducted in five primary schools and seven
      high schools, which were randomly selected in Henan province, China. A total of
      6792 students aged 8-17 years old were given a questionnaire that included the
      adult diagnostic criteria of RLS proposed by the International Restless Legs
      Study Group. Subjects who answered "yes" to all four questions were selected for
      a face-to-face interview to confirm RLS diagnosis. Individuals with definite RLS
      were then administered another questionnaire to survey RLS symptoms and perceived
      consequences. The prevalence of definite RLS in Chinese children and adolescents
      was 2.2 % (141/6437), with a prevalence of 1.8 % in the 8-11 years old age group
      and 2.4 % in the 12-17 years old age group. RLS was found to be more prevalent in
      females (2.7 %) than in males (1.7 %) (P = 0.008), and the prevalence of RLS was
      determined to increase with age. Sleep disturbance was the most common symptom of
      RLS in children and adolescents. Various consequences were attributed to RLS,
      with participants reporting that they dreaded the arrival of evening/night most
      frequently, followed by the description that RLS had a negative impact on mood.
      These data suggest that RLS is prevalent in Chinese children and adolescents, and
      that those affected by this disorder suffer from disruptions to sleep and daytime
      function.

PMID- 25847087
TI  - Prognosis of implant longevity in terms of annual bone loss: a methodological
      finite element study.
AB  - Dental implant failure is mainly the consequence of bone loss at peri-implant
      area. It usually begins in crestal bone. Due to this gradual loss, implants
      cannot withstand functional force without bone overload, which promotes
      complementary loss. As a result, implant lifetime is significantly decreased. To
      estimate implant success prognosis, taking into account 0.2 mm annual bone loss
      for successful implantation, ultimate occlusal forces for the range of commercial
      cylindrical implants were determined and changes of the force value for each
      implant due to gradual bone loss were studied. For this purpose, finite element
      method was applied and von Mises stresses in implant-bone interface under 118.2 N
      functional occlusal load were calculated. Geometrical models of mandible segment,
      which corresponded to Type II bone (Lekholm & Zarb classification), were
      generated from computed tomography images. The models were analyzed both for
      completely and partially osseointegrated implants (bone loss simulation). The
      ultimate value of occlusal load, which generated 100 MPa von Mises stresses in
      the critical point of adjacent bone, was calculated for each implant. To estimate
      longevity of implants, ultimate occlusal loads were correlated with an
      experimentally measured 275 N occlusal load (Mericske-Stern & Zarb). These
      findings generally provide prediction of dental implants success.

PMID- 25847086
TI  - Ecological host fitting of Trypanosoma cruzi TcI in Bolivia: mosaic population
      structure, hybridization and a role for humans in Andean parasite dispersal.
AB  - An improved understanding of how a parasite species exploits its genetic
      repertoire to colonize novel hosts and environmental niches is crucial to
      establish the epidemiological risk associated with emergent pathogenic genotypes.
      Trypanosoma cruzi, a genetically heterogeneous, multi-host zoonosis, provides an
      ideal system to examine the sylvatic diversification of parasitic protozoa. In
      Bolivia, T. cruzi I, the oldest and most widespread genetic lineage, is pervasive
      across a range of ecological clines. High-resolution nuclear (26 loci) and
      mitochondrial (10 loci) genotyping of 199 contemporaneous sylvatic TcI clones was
      undertaken to provide insights into the biogeographical basis of T. cruzi
      evolution. Three distinct sylvatic parasite transmission cycles were identified:
      one highland population among terrestrial rodent and triatomine species, composed
      of genetically homogenous strains (Ar = 2.95; PA/L = 0.61; DAS = 0.151), and two
      highly diverse, parasite assemblages circulating among predominantly arboreal
      mammals and vectors in the lowlands (Ar = 3.40 and 3.93; PA/L = 1.12 and 0.60;
      DAS = 0.425 and 0.311, respectively). Very limited gene flow between neighbouring
      terrestrial highland and arboreal lowland areas (distance ~220 km; FST = 0.42 and
      0.35) but strong connectivity between ecologically similar but geographically
      disparate terrestrial highland ecotopes (distance >465 km; FST = 0.016-0.084)
      strongly supports ecological host fitting as the predominant mechanism of
      parasite diversification. Dissimilar heterozygosity estimates (excess in
      highlands, deficit in lowlands) and mitochondrial introgression among lowland
      strains may indicate fundamental differences in mating strategies between
      populations. Finally, accelerated parasite dissemination between densely
      populated, highland areas, compared to uninhabited lowland foci, likely reflects
      passive, long-range anthroponotic dispersal. The impact of humans on the risk of
      epizootic Chagas disease transmission in Bolivia is discussed.

PMID- 25847088
TI  - Brain metabolism in minimal hepatic encephalopathy assessed by 3.0-Tesla magnetic
      resonance spectroscopy.
AB  - AIM: To examine whether the brain exhibits metabolic disorder prior to overt
      hepatic encephalopathy in patients with liver cirrhosis (LC), the intracerebral
      glutamine and myo-inositol levels were determined using 3.0-Tesla (T)(1) H
      (proton) magnetic resonance spectroscopy (MRS). METHODS: We tested 21 LC
      patients, including seven patients with minimal hepatic encephalopathy (MHE).
      RESULTS: No significant differences were noted between the two patient groups in
      terms of the severity of LC, levels of blood ammonia or levels of blood or liver
      enzymes. In the MHE group, the levels of brain glutamine were significantly
      higher than those in the non-MHE group, whereas the levels of brain myo-inositol
      were significantly lower. This demonstrated that MHE patients were already
      exhibiting metabolic disorder in the brain, similar to those observed during
      overt hepatic encephalopathy. CONCLUSION: A quantitative analysis of this
      phenomenon using MRS may contribute to an early and objective diagnosis of MHE.

PMID- 25847089
TI  - Impact of n-3 polyunsaturated fatty acids in predicting ischemia/reperfusion
      injury and progression of myocardial damage after reperfusion in patients with ST
      segment elevation acute myocardial infarction.
AB  - BACKGROUND: In animal models of acute myocardial infarction, n-3 polyunsaturated
      fatty acids (PUFAs) administered before coronary occlusion have been suggested to
      prevent induction of ventricular arrhythmia and limit infarct size. However, the
      relation between the serum levels of n-3 PUFAs and ischemia/reperfusion (I/R)
      injury remains unclear. METHODS: 211 patients with ST-segment elevation acute
      myocardial infarction received emergency percutaneous coronary intervention (PCI)
      within 6h from the onset. The patients were divided into two groups according to
      the sum of serum eicosapentaenoic acid (EPA) levels and docosahexaenoic acid
      (DHA) levels before PCI: group L (n=106), EPA+DHA <155MUg/ml and group H (n=105),
      EPA+DHA >=155MUg/ml. The Selvester QRS-scoring system was used to estimate the
      serial change in infarct size. RESULTS: Time to reperfusion was similar between
      the 2 groups. The QRS score before PCI was higher in group L than in group H
      (2.42+/-2.00 vs 1.85+/-2.01, p=0.015). The proportion of patients with I/R injury
      immediately after reperfusion, defined as reperfusion ventricular arrhythmias
      (25% vs 11%, p=0.006) and ST-segment re-elevation (44% vs 22%, p<0.001), was also
      higher in group L than in group H, followed by a greater increment in the QRS
      score during PCI (3.51+/-2.51 vs 2.54+/-1.91, p=0.006) and higher peak levels of
      creatinine phosphokinase (3552+/-241U/L vs 2660+/-242U/L, p<0.01). On
      multivariate analysis, serum level of EPA+DHA was an independent predictor of
      reperfusion injury (odds ratio 0.985, p=0.032). CONCLUSION: Serum level of n-3
      PUFAs before PCI may be a predictor of I/R injury and the resultant extent of
      myocardial damage. These findings suggest a protective effect of serum n-3 PUFAs
      on ischemic myocardium.

PMID- 25847090
TI  - Clinical and angiographic outcomes of paclitaxel-eluting coronary stent
      implantation in hemodialysis patients: A prospective multicenter registry: The
      OUCH-TL study (outcome in hemodialysis of TAXUS Liberte).
AB  - BACKGROUND: The outcome of percutaneous coronary intervention (PCI) has been
      reported to be poor in hemodialysis (HD) patients even in the drug-eluting stent
      era. We have reported relatively poor outcomes after sirolimus-eluting stent
      implantation in the OUCH study. METHODS: The OUCH-TL study is a prospective, non
      randomized, single-arm registry designed to assess the results of paclitaxel
      eluting stent (PES) in HD patients with follow-up quantitative coronary
      angiography analysis. The primary endpoint was the occurrence of target-vessel
      failure (TVF) defined as cardiac death, myocardial infarction (MI), and target
      vessel revascularization (TVR) at 12 months. RESULTS: A total of 119 patients
      with 154 lesions were enrolled (one withdrawal). Mean age was 65+/-10 years, male
      gender was 79%, 89% of cases had stable coronary disease. Diabetic nephropathy
      was diagnosed in 61% of the patients. American College of Cardiology/American
      Heart Association type B2/C accounted for 96% of lesions and 22.7% of lesions
      were treated with Rotablator (Boston Scientific Corporation, Natick, MA, USA).
      Rates of TVF, death, MI, stent thrombosis and TVR at 12 months were 20.2%, 5.9%,
      5.0%, 1.4%, and 12.6%, respectively. TVR was performed in 8.4% of the patients up
      to 12 months. Late loss in-stent was 0.48+/-0.61mm, and late loss in-segment was
      0.37+/-0.61mm at 9 months. Binary restenosis in-stent was 10.3% and in-segment
      was 14.5%. CONCLUSIONS: Outcomes of PES implantation in hemodialysis patients
      appears comparable to those of non-hemodialysis patients.

PMID- 25847091
TI  - Pre-procedural evaluation of the left atrial anatomy in patients referred for
      catheter ablation of atrial fibrillation.
AB  - BACKGROUND: Cardiac computed tomography (CT) provides accurate imaging of the
      pulmonary vein (PV) and left atrial (LA) anatomy. This study aimed to evaluate
      the prevalence and morphological characteristics of anatomical variants that
      could influence atrial fibrillation (AF) ablation procedures. METHODS AND
      RESULTS: One thousand forty consecutive patients (62+/-10 years, 243 female, 644
      paroxysmal AF) undergoing pre-procedural imaging with a 320-row CT and their
      first AF ablation procedure were analyzed. A total of 194 (18.7%) patients had
      anatomical variants. Left, right, and inferior common PVs were observed in 118,
      5, and 6 patients, respectively. Three right and left PVs were observed in 44 and
      4 patients, respectively. Three patients had remnants of PVs after lobectomies,
      and significant PV stenosis was observed in one. Supernumerary PVs that drained
      into the LA and diverticula were observed in eight patients. One patient had a
      string-like structure connecting the LA septum and posterior LA, and the others
      had membranous structures incompletely compartmentalizing the LA. Three patients
      had persistent left superior vena cavae, two strong deviations of the LA and PVs,
      and one dexiocardia. All patients underwent successful PV isolation during the
      index procedure. CONCLUSIONS: Patients referred for AF ablation often have
      anatomical variants, which could influence the procedure. This information might
      aid in planning procedural strategies, and reducing unexpected procedural
      complications in AF ablation.

PMID- 25847092
TI  - Quantifying space use of breeders and floaters of a long-lived species using
      individual movement data.
AB  - To date, animal movement studies have mostly analysed the movement behaviours of
      individuals at specific times of their lives, but we lack detailed information on
      how individual movements may be affected by the various and different changes
      that individuals experience throughout their life (e.g. life history phases,
      experience, age). Here, we attempt to identify differences in home range and
      movement behaviour between two different statuses, disperser vs. breeder, of a
      long-lived species (the eagle owl Bubo bubo). Information on home range and
      movement behaviour between different stages of an individual life are crucial for
      species conservation and management, as well as for basic knowledge on space use
      and rhythm of activity. Does the transition from an exploratory stage to moving
      within more familiar surroundings call for changes in the movement behaviour? We
      observed notable differences during the two stages of the owls' lives, with
      individuals having different home range behaviours and rhythms of activity
      depending on their social status. Significant differences in home range behaviour
      between the sexes began only with the acquisition of a breeding site. Breeders
      showed larger home ranges than dispersing individuals, although nightly variation
      of home ranges size was higher for dispersers than for breeders. Finally,
      dispersers were active throughout the night, whereas breeders displayed a less
      active movement phase at both the beginning and end of the night. Our results
      demonstrate it is important to consider individual variations in space use and
      movement behaviour due to the different life history phases that they attain
      during their lifetime. The knowledge of the different needs of a species across
      life stages may represent an important tool for species conservation because each
      phase of an individual life may need different requirements. 

PMID- 25847093
TI  - Massed and distributed repetition of natural scenes: Brain potentials and
      oscillatory activity.
AB  - Neural measures of repetition can result in either repetition suppression or
      enhancement effects, with enhancement sometimes interpreted as indicating
      episodic retrieval, rather than stimulus habituation. Here, we manipulated
      whether repetitions were massed (consecutive) or distributed (intermixed) and
      measured event-related potentials and oscillatory activity, investigating the
      question of whether there is evidence of "spontaneous" episodic retrieval for
      distributed, but not massed, repetition. Results showed that distributed
      repetition uniquely prompted a significant centroparietal old-new effect as well
      as enhanced theta, compared to either novel presentations or massed repetitions,
      consistent with a hypothesis of spontaneous retrieval. Massed repetition, on the
      other hand, prompted repetition suppression and reduction of the N2/P2. Taken
      together, the data suggest that distributed repetition may facilitate later
      memory performance because it spontaneously retrieves prior representations. 

PMID- 25847094
TI  - Testing for polygenic effects in genome-wide association studies.
AB  - To confirm associations with a large number of single nucleotide polymorphisms
      (SNPs), each with only a small effect size, as hypothesized in the polygenic
      theory for schizophrenia, the International Schizophrenia Consortium (2009,
      Nature 460:748-752) proposed a polygenic risk score (PRS) test and demonstrated
      its effectiveness when applied to psychiatric disorders. The basic idea of the
      PRS test is to use a half of the sample to select and up-weight those more likely
      to be associated SNPs, and then use the other half of the sample to test for
      aggregated effects of the selected SNPs. Intrigued by the novelty and increasing
      use of the PRS test, we aimed to evaluate and improve its performance for GWAS
      data. First, by an analysis of the PRS test, we point out its connection with the
      Sum test [Chapman and Whittaker, Genet Epidemiol 32:560-566; Pan, Genet Epidemiol
      33:497-507]; given the known advantages and disadvantages of the Sum test, this
      connection motivated the development of several other polygenic tests, some of
      which may be more powerful than the PRS test under certain situations. Second,
      more importantly, to overcome the low statistical efficiency of the data
      splitting strategy as adopted in the PRS test, we reformulate and thus modify the
      PRS test, obtaining several adaptive tests, which are closely related to the
      adaptive sum of powered score (SPU) test studied in the context of rare variant
      analysis [Pan et al., 2014, Genetics 197:1081-1095]. We use both simulated data
      and a real GWAS dataset of alcohol dependence to show dramatically improved power
      of the new tests over the PRS test; due to its superior performance and
      simplicity, we recommend the whole sample-based adaptive SPU test for polygenic
      testing. We hope to raise the awareness of the limitations of the PRS test and
      potential power gain of the adaptive SPU test.

PMID- 25847095
TI  - Old sleeping Sicilian beauty: seed germination in the palaeoendemic Petagnaea
      gussonei (Spreng.) Rauschert (Saniculoideae, Apiaceae).
AB  - Petagnaea gussonei (Apiaceae) is a perennial herbaceous species endemic to
      northeast Sicily (Nebrodi Mountains). It is considered a remnant of the Sicilian
      Tertiary flora, and is endangered according to the Red List. There is no
      information in the literature about the germinability of its seeds, even though
      seed production is know to occur. The aim of this study was to obtain data to
      better understand seed germination of this species and its biological
      implications. Thus, several approaches were employed: vitality analyses,
      gibberellic acid supply, germination and soil microbial flora analyses via end
      point and qPCR. The results suggest that seed germination occurs after ca. 1.5
      years at a rate of ca. 11%. The seeds can be classified as physiologically
      dormant, and probably require prolonged cold stratification for germination.
      Because seed germination is low, it is likely that agamic reproduction represents
      an important mean for its conservation and survival. These results have important
      implications for P. gussonei survival and should be considered in possible re
      introduction attempts aimed at restoring threatened populations.

PMID- 25847096
TI  - Links between genome replication and chromatin landscapes.
AB  - Post-embryonic organogenesis in plants requires the continuous production of
      cells in the organ primordia, their expansion and a coordinated exit to
      differentiation. Genome replication is one of the most important processes that
      occur during the cell cycle, as the maintenance of genomic integrity is of
      primary relevance for development. As it is chromatin that must be duplicated, a
      strict coordination occurs between DNA replication, the deposition of new
      histones, and the introduction of histone modifications and variants. In turn,
      the chromatin landscape affects several stages during genome replication. Thus,
      chromatin accessibility is crucial for the initial stages and to specify the
      location of DNA replication origins with different chromatin signatures. The
      chromatin landscape also determines the timing of activation during the S phase.
      Genome replication must occur fully, but only once during each cell cycle. The re
      replication avoidance mechanisms rely primarily on restricting the availability
      of certain replication factors; however, the presence of specific histone
      modifications are also revealed as contributing to the mechanisms that avoid re
      replication, in particular for heterochromatin replication. We provide here an
      update of genome replication mostly focused on data from Arabidopsis, and the
      advances that genomic approaches are likely to provide in the coming years. The
      data available, both in plants and animals, point to the relevance of the
      chromatin landscape in genome replication, and require a critical evaluation of
      the existing views about the nature of replication origins, the mechanisms of
      origin specification and the relevance of epigenetic modifications for genome
      replication.

PMID- 25847097
TI  - Complex alterations in microglial M1/M2 markers during the development of
      epilepsy in two mouse models.
AB  - OBJECTIVE: To characterize the changes in microglial proinflammatory M1 and
      antiinflammatory M2 marker expression during epileptogenesis in the chronic
      pilocarpine and intrahippocampal kainate models. METHODS: M1-activated microglia
      express proinflammatory cytokines driving infiltration of cells, whereas M2
      activated microglia are more reparative, promoting phagocytosis of debris and
      expression of proteins associated with cellular stability and repair. Microglial
      markers were characterized as acute (3 days after status epilepticus [SE]), early
      chronic (21 days post-SE), and late chronic epileptic (5-12 months post-SE) time
      points. Following pilocarpine-SE, microglial markers were assessed by flow
      cytometry. Quantitative real-time polymerase chain reaction (RT-PCR) was used to
      measure messenger RNA (mRNA) levels of selected M1 (interleukin [IL] 1beta, tumor
      necrosis factor alpha [TNFalpha] cluster of differentiation [CD],CD16, and CD86),
      interleukin-6 [IL-6], interleukin-12 [IL-12], Fc receptors 16, and CD86) and M2
      (arginase 1 [Arg1], chitinase-3-like protein [Ym1], found in inflammatory zone
      [FIZZ-1] [FIZZ-1], mannose receptor C type-1 [CD206], interleukin-4 [IL-4], and
      interleukin-10 (IL-10)) markers in both models. Video-electroencephalography
      (EEG) recordings were used to quantify late chronic seizure frequency. RESULTS:
      Three days post-SE microglia in the pilocarpine model expressed M1 and M2
      markers, but only M1 markers were upregulated after kainate-induced SE. After 3
      weeks, M1/M2 marker expression was largely ablated in the hippocampal formation
      of both models. Small mRNA level increases of CD11b, glial fibrillary acidic
      protein (GFAP), and IL-1beta were found in the pilocarpine model, consistent with
      IL-1beta contributing to spontaneous seizures, whereas mRNA levels of TNFalpha
      and Ym1 were decreased. In the late chronic phase, some M1/M2 markers, IL-1beta,
      TNFalpha, Arg1, Ym1, and CD206, resurged in the kainate, but not pilocarpine
      model, which may reflect and/or contribute to highly frequent seizures in kainate
      SE mice. SIGNIFICANCE: The common M1 upregulation acutely post-SE may signal a
      role early in epileptogenesis, with a more pure "inflamed" central nervous system
      state after kainate-SE, potentially contributing to the development of more
      frequent seizures. The difference may also be due to the contribution of
      peripheral inflammation after pilocarpine injection. In summary, the microglial
      inflammatory response during epileptogenesis is complex, varies between models,
      and appears to correlate with chronic seizure frequency.

PMID- 25847098
TI  - Adverse Perinatal Outcomes among Immigrant Women from Ethiopia in Israel.
AB  - BACKGROUND: Immigration from Ethiopia to Israel started about 30 years ago. We
      aimed to compare birth outcomes between Israeli women of Ethiopian origin and
      Israeli-born, non-Ethiopian women. We hypothesized a higher frequency of adverse
      birth outcomes among Ethiopian women and a trend of improvement among those who
      were raised in Israel since early childhood. METHODS: This is a descriptive
      study, comparing birth outcomes of Ethiopian (n = 1,319) and non-Ethiopian women
      (n = 27,307) who gave birth in a medical center in Central Israel in 2002 to
      2009. Ethiopian women were further categorized by age at immigration. Logistic
      regressions were constructed to compare the incidence of adverse birth outcomes
      between Ethiopian and non-Ethiopian women, controlling for potential confounders.
      RESULTS: Ethiopian women had about twice the incidence of very and extremely
      preterm births, compared with non-Ethiopians. Ethiopian women had twice the odds
      for neonates who were either small for gestational age or had low 5-minute Apgar
      scores. Ethiopian women had about threefold increased risk of stillbirths (OR 2.9
      [95% CI 1.87-4.49]). No trend of improvement was noted for women who were raised
      in Israel from early childhood. CONCLUSION: Ethiopian women are at increased risk
      of adverse birth outcomes. Future research is needed to investigate the
      underlying causes for the increased risks and lack of improvement among those who
      were raised in Israel that will lead to effective interventions.

PMID- 25847099
TI  - Distinct clinical and radiographic characteristics of moyamoya disease amongst
      European Caucasians.
AB  - BACKGROUND AND PURPOSE: Occlusive cerebrovascular moyamoya disease (MMD) is rare
      and has been characterized mainly in Asian countries, so far. In recent years,
      MMD has been increasingly reported worldwide, raising the question whether its
      clinical presentation would vary amongst different ethnic backgrounds. Here, a
      homogeneous series of 153 patients with MMD are reported and the specific
      clinical features of this rare disease amongst European Caucasians are
      highlighted. METHODS: A total of 153 European Caucasians with MMD who were
      treated in our institution between 1997 and 2014 were retrospectively identified.
      Demographic data, clinical symptoms, angiographic characteristics and functional
      hemodynamic studies were analyzed. RESULTS: Moyamoya disease presented with a
      female predominance of 2,9:1.,78% presented with a typical MMD, 17% with a
      unilateral MMD and 5% with an atypical MMD. 16% of our patients belonged to the
      pediatric population. Overall, 81% and 8.5% of our cohort presented initially
      with ischaemic and hemorrhagic manifestation, respectively. The rate of
      hemorrhagic manifestation of MMD amongst the pediatric group was slightly higher
      (12%). Angiographic analysis revealed steno-occlusive involvement of the
      posterior circulation in 34% with a higher involvement in pediatric patients
      (64%) compared to adults (28%). CONCLUSIONS: The characterization of our
      homogeneous European Caucasian cohort reveals several significant differences
      compared to Asian cohorts. In contrast, MMD presents similarly amongst European
      and North American cohorts, suggesting that non-Asian MMD is characterized by
      distinct clinical features.

PMID- 25847100
TI  - Towards solar energy storage in the photochromic dihydroazulene-vinylheptafulvene
      system.
AB  - One key challenge in the field of exploitation of solar energy is to store the
      energy and make it available on demand. One possibility is to use photochromic
      molecules that undergo light-induced isomerization to metastable isomers. Here we
      present efforts to develop solar thermal energy storage systems based on the
      dihydroazulene (DHA)/vinylheptafulvene (VHF) photo/thermoswitch. New DHA
      derivatives with one electron-withdrawing cyano group at position 1 and one or
      two phenyl substituents in the five-membered ring were prepared by using
      different synthetic routes. In particular, a diastereoselective reductive removal
      of one cyano group from DHAs incorporating two cyano groups at position 1 turned
      out to be most effective. Quantum chemical calculations reveal that the
      structural modifications provide two benefits relative to DHAs with two cyano
      groups at position 1: 1) The DHA-VHF energy difference is increased (i.e., higher
      energy capacity of metastable VHF isomer); 2) the Gibbs free energy of activation
      is increased for the energy-releasing VHF to DHA back-reaction. In fact,
      experimentally, these new derivatives were so reluctant to undergo the back
      reaction at room temperature that they practically behaved as DHA to VHF one-way
      switches. Although lifetimes of years are at first attractive, which offers the
      ultimate control of energy release, for a real device it must of course be
      possible to trigger the back-reaction, which calls for further iterations in the
      future. 

PMID- 25847101
TI  - Modulation of pumping rate by two species of marine bivalve molluscs in response
      to neurotransmitters: Comparison of in vitro and in vivo results.
AB  - Most studies regarding the neuroanatomy and neurophysiology of molluscan ctenidia
      have focused on isolated ctenidial tissue preparations. This study investigated
      how bivalve molluscs modulate their feeding rates by examining the effects of a
      variety of neurotransmitters, including serotonin, dopamine, and the dopamine
      agonist apomorphine on both isolated ctenidial tissue and in intact members of
      two commercially important bivalve species: the blue mussel, Mytilus edulis; and
      the bay scallop Argopecten irradians. In particular, we examined the effect of
      changes in: 1) beat of the lateral cilia (in vitro), 2) distance between
      ctenidial filaments and/or plicae (in vivo), and 3) diameter of the siphonal
      openings (in vivo) on alteration of bulk water flow through the mantle cavity.
      Important differences were found between isolated tissue and whole animals, and
      between species. Drugs that stimulated ciliary beat in vitro did not increase
      water processing rate in vivo. None of the treatments increased water flow
      through the mantle cavity of intact animals. Results suggest that A. irradians
      was primarily modulating lateral ciliary activity, while M. edulis appeared to
      have a number of ways to control water processing activity, signifying that the
      two species may have different compensatory and regulatory mechanisms controlling
      feeding activity. 

PMID- 25847102
TI  - The distance between breast cancer and the skin is associated with axillary nodal
      metastasis.
AB  - BACKGROUND AND OBJECTIVES: More superficially located tumors may be more likely
      than deeper tumors to metastasize to the axillary nodes via the lymphatics. The
      aim of this study was to determine whether breast cancer distance from the skin
      affects axillary node metastasis, ipsilateral breast cancer recurrence, or
      recurrence-free survival. MATERIALS AND METHODS: A total of 1,005 consecutive
      patients with breast cancer who underwent surgery between January 2003 and
      December 2009 were selected. The distance of the tumor from the skin was measured
      from the skin to the most anterior hypoechoic leading edge of the lesion.
      RESULTS: In total, 603 (68%) patients had no axillary nodal metastasis, and 288
      (32%) had axillary nodal metastasis. A breast cancer distance from the skin <3 mm
      induced more axillary nodal metastasis (P = 0.039). However, no significant
      correlation was observed between breast cancer distance from the skin <3 mm and
      ipsilateral breast cancer recurrence (P = 0.788) or recurrence-free survival (P =
      0.353). CONCLUSIONS: Breast cancers located closer to the skin had a higher
      incidence of axillary nodal metastasis. Therefore, tumor distance from the skin
      should be considered when evaluating a patient with breast cancer and considering
      the risk of nodal metastasis.

PMID- 25847103
TI  - The occurrence and ecological risk assessment of phthalate esters (PAEs) in urban
      aquatic environments of China.
AB  - Phthalate esters (PAEs) are widely used in the manufacturing of plastics, and the
      demand for PAEs has grown rapidly, especially in China. This trend will lead to
      much more environmental PAE contamination. PAEs are listed as priority substances
      in the European Union and are therefore subject to ecological risk assessments.
      This paper reviews the literature concerning the pollution status of PAEs and
      their ecological risk to aquatic environments. Risk quotients (RQs) based on the
      predicted no effect concentration and PAE concentrations in aquatic environments
      demonstrated significant (10 <= RQ < 100) or expected (RQ >= 100) potential
      adverse effects for algae, Daphnia, and fish in aquatic environments near PAE
      based industrial and urban areas. Thus, the ecological risk of PAEs in Chinese
      aquatic environments should be considered, especially in areas where commercial
      plastics are produced.

PMID- 25847104
TI  - Assessment for water quality by artificial neural network in Daya Bay, South
      China Sea.
AB  - In this study, artificial neural network such as a self-organizing map (SOM) was
      used to assess for the effects caused by climate change and human activities on
      the water quality in Daya Bay, South China Sea. SOM has identified the
      anthropogenic effects and seasonal characters of water quality. SOM grouped the
      four seasons as four groups (winter, spring, summer and autumn). The Southeast
      Asian monsoons, northeasterly from October to the next April and southwesterly
      from May to September have also an important influence on the water quality in
      Daya Bay. Spatial pattern is mainly related to anthropogenic activities and
      hydrodynamics conditions. In spatial characteristics, the water quality in Daya
      Bay was divided into two groups by chemometrics. The monitoring stations (S3, S8,
      S10 and S11) were in these area (Dapeng Ao, Aotou Harbor) and northeast parts of
      Daya Bay, which are areas of human activity. The thermal pollution has been
      observed near water body in Daya Bay Nuclear Power Plant (S5). The rest of the
      monitoring sites were in the south, central and eastern parts of Daya Bay, which
      are areas that experience water exchanges from South China Sea. The results of
      this study may provide information on the spatial and temporal patterns in Daya
      Bay. Further research will be carry out more research concerning functional
      changes in the bay ecology with respect to changes in climatic factor, human
      activities and bay morphology in Daya Bay.

PMID- 25847105
TI  - Ecotoxicological evaluation of propranolol hydrochloride and losartan potassium
      to Lemna minor L. (1753) individually and in binary mixtures.
AB  - Antihypertensive pharmaceuticals, including the beta-blockers, are one of the
      most detected therapeutic classes in the environment. The ecotoxicity of
      propranolol hydrochloride and losartan potassium was evaluated, both individually
      and combined in a binary mixture, by using the Lemna minor growth inhibition
      test. The endpoints evaluated in the single-pharmaceutical tests were frond
      number, total frond area and fresh weight. For the evaluation of the mixture
      toxicity, the selected endpoint was frond number. Water quality criteria values
      (WQC) were derived for the protection of freshwater and saltwater pelagic
      communities regarding the effects induced by propranolol and losartan using
      ecotoxicological data from the literature, including our data. The risks
      associated with both pharmaceutical effects on non-target organisms were
      quantified through the measured environmental concentration (MEC)/predicted-no
      effect concentration (PNEC) ratios. For propranolol, the total frond area was the
      most sensitive endpoint (EC50 = 77.3 mg L(-1)), while for losartan there was no
      statistically significant difference between the endpoints. Losartan is only
      slightly more toxic than propranolol. Both concentration addition and independent
      action models overestimated the mixture toxicity of the pharmaceuticals at all
      the effect concentration levels evaluated. The joint action of both
      pharmaceuticals showed an antagonistic interaction to L. minor. Derived WQC
      assumed lower values for propranolol than for losartan. The MEC/PNEC ratios
      showed that propranolol may pose a risk for the most sensitive aquatic species,
      while acceptable risks posed by losartan were estimated for most of aquatic
      matrices. To the authors knowledge these are the first data about losartan
      toxicity for L. minor.

PMID- 25847106
TI  - Acaricide-impaired functional predation response of the phytoseiid mite
      Neoseiulus baraki to the coconut mite Aceria guerreronis.
AB  - Acaricides may interfere with a myriad of interactions among arthropods,
      particularly predator-prey interactions. The coconut mite, Aceria guerreronis
      Keifer (Acari: Eriophyidae), and its phytoseiid predator, Neoseiulus baraki
      (Athias-Henriot) (Acari: Phytoseiidae), provide an opportunity to explore such
      interference because the former is a key coconut pest species that requires both
      predation and acaricide application for its management. The objective of the
      present study was to assess the effect of the acaricides abamectin, azadirachtin
      and fenpyroximate on the functional response of N. baraki to A. guerreronis
      densities. The following prey densities were tested: 5, 10, 20, 40 and 80 preys.
      The type of functional response and prey handling time (Th) were not altered by
      the acaricides. However, the attack rate (a') was modified by abamectin and
      fenpyroximate, and the consumption peak was reduced by abamectin. All of the
      acaricides allowed for the maintenance of the predator in the field, but exposure
      to abamectin and fenpyroximate compromised prey consumption. 

PMID- 25847107
TI  - Revitalizing traditional ecological knowledge: a study in an Alpine rural
      community.
AB  - This study aims to contribute to the debate on the value and the role of
      ecological knowledge in modern conservation strategies, with reference to the
      results of a case study conducted in the community of Montagne, located within a
      World Heritage site in the Italian Alps. This community is a paradigmatic example
      of the multiple transformations experienced by cultural landscapes in Alpine
      areas under the influence of global change. This study seeks to understand
      whether ecological knowledge is still in place in the community, and what the
      relationship is between the knowledge transmission and land use and social
      changes that have occurred in recent decades. To that end, the community is
      described by identifying the key variables (social, institutional, and
      ecological) that have historically shaped the landscape and the future priorities
      of the residents. Forest expansion, the most significant change in land use in
      the last 60 years, is analyzed using aerial photos; changes in biodiversity
      related knowledge in the community are quantified by analyzing the inter
      generational differences in plant species recognition. Results are discussed in
      the context of the current situation of the Montagne community, and the
      recommendation is made that policies and actions to promote traditional
      ecological knowledge protection or recovery in Europe be viewed as an important
      part of the recovery of community sovereignty and vitality. Lastly, concrete
      actions that can be implemented in our case study are proposed.

PMID- 25847108
TI  - The Cultural Dimensions of Freshwater Wetland Assessments: Lessons Learned from
      the Application of US Rapid Assessment Methods in France.
AB  - Given the recent strengthening of wetland restoration and protection policies in
      France, there is need to develop rapid assessment methods that provide a cost
      effective way to assess losses and gains of wetland functions. Such methods have
      been developed in the US and we tested six of them on a selection of contrasting
      wetlands in the Isere watershed. We found that while the methods could
      discriminate sites, they did not always give consistent rankings, thereby
      revealing the different assumptions they explicitly or implicitly incorporate.
      The US assessment methods commonly use notions of "old-growth" or "pristine" to
      define the benchmark conditions against which to assess wetlands. Any reference
      based assessment developed in the US would need adaptation to work in the French
      context. This could be quite straightforward for the evaluation of hydrologic
      variables as scoring appears to be consistent with the best professional judgment
      of hydrologic condition made by a panel of French local experts. Approaches to
      rating vegetation condition and landscape context, however, would require
      substantial reworking to reflect a novel view of reference standard. Reference
      standard in the European context must include acknowledgement that many of the
      best condition and biologically important wetland types in France are the product
      of intensive, centuries-long management (mowing, grazing, etc.). They must also
      explicitly incorporate the recent trend in ecological assessment to focus
      particularly on the wetland's role in landscape-level connectivity. These context
      specific, socio-cultural dimensions must be acknowledged and adjusted for when
      adapting or developing wetland assessment methods in new cultural contexts. 

PMID- 25847109
TI  - Tibial nerve F-wave recordings.
AB  - INTRODUCTION: Tibial F-wave recordings are remarkable for their complexity and
      persistence. We postulate that the signal recorded by the E2 (reference)
      electrode causes this pattern. METHODS: Tibial F-wave recordings were made from
      the abductor hallucis (AH) muscle using the standard montage in 10 subjects.
      Additional far-field simultaneous F-wave recordings were made from the AH, the
      base of the large toe, and the base of the small toe with the E2 placed on the
      contralateral foot. RESULTS: F-wave recordings made in the standard manner and
      from the base of the large or small toes showed complex waveforms and similar
      latencies. Recordings made from the AH-contralateral foot had simple waveforms in
      most subjects; in 2 subjects the latencies were longer, and 1 showed reduced
      persistence. CONCLUSIONS: The tibial F-waves are composed primarily of volume
      conducted recordings of the tibial-innervated foot muscles from the E2 electrode.

PMID- 25847110
TI  - Extracardiac anomalies in prenatally diagnosed heterotaxy syndrome.
AB  - OBJECTIVE: To assess the incidence and impact of extracardiac anomalies on the
      prognosis of fetuses with heterotaxy syndrome. METHODS: All fetuses diagnosed
      with heterotaxy syndrome by three experienced examiners over a period of 14 years
      (1999-2013) were reviewed retrospectively. RESULTS: In total, 165 fetuses with
      heterotaxy syndrome were diagnosed in the study period. One hundred and fifty
      (90.9%) had cardiac defects; extracardiac anomalies that did not involve the
      spleen were present in 26/165 (15.8%) cases. Of the total study cohort,
      termination of pregnancy was performed in 49 (29.7%) cases, intrauterine death
      occurred in 11 (6.7%), postnatal death occurred in 38 (23.0%) and 67 (40.6%) were
      alive at the latest follow-up, resulting in a total perinatal and pediatric
      mortality of 59.4%. Among the 105 liveborn neonates, 15 (14.3%) had extracardiac
      anomalies with significant impact on the postnatal course: one neonate died
      following repair of an encephalocele, six had successful treatment for various
      types of intestinal malrotation and/or atresia and one underwent hiatal hernia
      repair; the remaining seven had biliary atresia, of which five died and the two
      survivors are awaiting liver transplantation. The status of the spleen was
      assessed in 93/105 liveborn children and was found to be abnormal in 84/93
      (90.3%). There were three cases of lethal sepsis, all associated with asplenia.
      Of the 38 postnatal deaths, 29 (76.3%) had a cardiac cause, seven (18.4%) had an
      extracardiac cause and in two (5.2%) the reason was uncertain. CONCLUSIONS:
      Although the leading causes of death in fetuses and children with heterotaxy
      syndrome are cardiac, a small subset of fetuses have extracardiac anomalies with
      significant impact on outcome. These anomalies often escape prenatal detection,
      and therefore neonates at risk should be monitored for bowel obstruction, biliary
      atresia and immune dysfunction in order to allow timely intervention through a
      multidisciplinary approach. Copyright (c) 2015 ISUOG. Published by John Wiley &
      Sons Ltd.

PMID- 25847111
TI  - Anatomical versus non-anatomical resection for hepatocellular carcinoma.
AB  - BACKGROUND: The optimal surgical resection method in patients with HCC to
      minimize the risk of local recurrence has not yet been determined. The aim of
      this study was to compare the prognosis following anatomical versus non
      anatomical hepatic resection for hepatocellular carcinoma (HCC). METHODS:
      Consecutive patients with HCC without macroscopic vascular invasion, treated by
      curative resection between 1981 and 2012 at Osaka Medical Centre, were included
      in this retrospective study. The outcomes of patients selected by propensity
      score matching were compared. RESULTS: Some 1102 patients were included, 577 in
      the anatomical and 525 in the non-anatomical resection group. By propensity score
      matching, 329 patients were selected into each group. Demographic, preoperative
      and tumour variables were similar between the propensity score-matched groups,
      including tumour size, tumour multiplicity, alpha-fetoprotein level and 15-min
      indocyanine green retention rate at 15 min. The incidence of microvascular
      invasion was higher in the matched anatomical resection group (P = 0.048).
      Stratified analysis of recurrence-free and overall survival rates revealed no
      statistically significant differences between the two propensity score-matched
      groups (P = 0.704 and P = 0.381 respectively). There was also no significant
      difference in the early recurrence rate within 2 years after resection between
      these groups (P = 0.726). Subset analysis of the early recurrence-free survival
      rate in patients with and without microvascular invasion revealed no significant
      differences between the groups (P = 0.312 and P = 0.479 respectively).
      CONCLUSION: The resection method had no impact on the risk of HCC recurrence or
      survival.

PMID- 25847112
TI  - Can drug effects explain the recent temporal increase in atonic postpartum
      haemorrhage?
AB  - BACKGROUND: Rates of postpartum haemorrhage and atonic postpartum haemorrhage
      have increased in several high-income countries. We carried out a study to
      examine if drug use in pregnancy, or drug and other interactions, explained this
      increase in postpartum haemorrhage. METHODS: The linked administrative and
      hospital databases of the Quebec Pregnancy Cohort were used to define a cohort of
      pregnant women in Quebec, Canada, from 1998 to 2009 (n = 138,704). Case-control
      studies on any postpartum haemorrhage and atonic postpartum haemorrhage were
      carried out within this population, with up to five controls randomly selected
      for each case after matching on index date and hospital of delivery (incidence
      density sampling). Conditional logistic regression was used to estimate the
      effects of drug use on postpartum haemorrhage and atonic postpartum haemorrhage.
      RESULTS: There was an unexpected non-linear, declining temporal pattern in
      postpartum haemorrhage and atonic postpartum haemorrhage between 1998 and 2009.
      Use of antidepressants (mainly selective serotonin reuptake inhibitors) was
      associated with higher rates of postpartum haemorrhage [adjusted rate ratio (aRR)
      1.48, 95% confidence interval (CI) 1.23, 1.77] and atonic postpartum haemorrhage
      [aRR 1.40, 95% CI 1.13, 1.74]. Thrombocytopenia was also associated with higher
      rates of postpartum haemorrhage [aRR 1.52, 95% CI 1.16, 2.00]. There were no
      statistically significant drug interactions. Adjustment for maternal factors and
      drug use had little effect on temporal trends in postpartum haemorrhage and
      atonic postpartum haemorrhage. CONCLUSIONS: Although antidepressant use and
      thrombocytopenia were associated with higher rates of atonic postpartum
      haemorrhage, antidepressant and other drug use did not explain temporal trends in
      postpartum haemorrhage.

PMID- 25847113
TI  - A maternally inherited 16p13.11-p12.3 duplication concomitant with a de novo SOX5
      deletion in a male patient with global developmental delay, disruptive and
      obsessive behaviors and minor dysmorphic features.
AB  - We detail here the clinical description and the family genetic study of a male
      patient with global developmental delay, disruptive and obsessive behaviors and
      minor dysmorphic features and a combination of two rare genetic variants: a
      maternally inherited 16p13.11-p12.3 duplication and a de novo 12p12.1 deletion
      affecting SOX5. The 16p13.11 microduplication has been implicated in several
      neurodevelopmental and behavioral disorders and is characterized by variable
      expressivity and incomplete penetrance. The causes of this variation in
      phenotypic expression are not fully clear, representing a challenge in genetic
      diagnosis and counseling. However, several authors have proposed the two-hit
      model as one of the underlying mechanisms for this phenotypic heterogeneity. Our
      data could also support this two-hit model in which the 16p13.11-p12.3
      duplication might contribute to the phenotype, not only as a single event but
      also in association with the SOX5 deletion. The SOX5 gene plays important roles
      in various developmental processes and has been associated with several
      neurodevelopmental disorders, mainly intellectual disability, developmental delay
      and language and/or speech delay as well as with behavior problems and dysmorphic
      features. However, many of the physical features and behavioral manifestations as
      well as language deficiencies present in our patient are consistent with those
      previously reported for SOX5 deletions. Patients carrying multiple genomic
      variants, as the one presented here, illustrate the difficulty in analyzing
      genotypes when the contribution of each variant results in overlapping phenotypes
      and/or, alternatively, in the modification of the clinical manifestations defined
      by the coexisting variant.

PMID- 25847116
TI  - Renal Autotransplantation in Lynch Syndrome: A Viable Option in a Patient With
      Contralateral Metachronous Ureteral Cancer.
AB  - The success of human kidney allotransplantation was realized over six decades
      ago. First described 50 years ago, renal autotransplantation has been utilized
      sparingly as a salvage procedure for patients at risk of losing renal function,
      either from a benign or malignant condition. While classically associated with
      colorectal malignancies, Lynch syndrome also carries a small yet significant risk
      for the development of ureteral carcinoma. For these patients who develop chronic
      kidney disease, allotransplantation may not be an option due to the lifelong risk
      of several malignancies. We report the first known case of renal
      autotransplantation in a patient with metachronous ureteral cancer due to Lynch
      syndrome. 

PMID- 25847117
TI  - Sensitive and rapid assessment of amyloid by oligothiophene fluorescence in
      subcutaneous fat tissue.
AB  - Systemic amyloidosis (SA) is often diagnosed late. Combining clinical and
      biochemical biomarkers is necessary for raising suspicion of disease. Fine needle
      aspiration (FNA) of subcutaneous fat enables SA detection by Congo red staining.
      The luminescent conjugated probe heptameric formic thiophene acetic acid (h-FTAA)
      is a sensitive alternative to Congo red-staining of tissue samples. Our objective
      was to compare h-FTAA fluorescence with the Congo red stain for amyloid detection
      in FNA-obtained fat tissue. Herein, we studied samples from 57 patients with
      established SA (19 with AA, 20 with AL, and 18 with ATTR) and 17 age-matched
      controls (34-75 years). Positivity for h-FTAA was graded according to a Congo red
      based grading scale ranging from 0 to 4+. Amyloid grading by both methods
      correlated strongly (r = 0.87). Here h-FTAA was positive in 53 of 54 Congo red
      positive cases (sensitivity 98%) and h-FTAA was negative in 7 of 17 Congo red
      negative controls (specificity 41%), but was also positive for 3 Congo red
      negative SA cases. We conclude that h-FTAA fluorescence is more sensitive than
      Congo red staining in this small exploratory study of fat tissue samples,
      implicating potential sensitivity for prodromal amyloidosis, but is less specific
      for clinical amyloidosis defined by Congo red positivity. Given its simplicity h
      FTAA staining may therefore be the most appropriate method for rapid screening of
      fat tissue samples but should presently treat grade 1+ as only suggestive,
      whereas 2+ or higher as positive for amyloidosis. Parallel assessment of h-FTAA
      and Congo red staining appears highly promising for clinical applications. 

PMID- 25847118
TI  - Methyl aminolevulinate photodynamic therapy for actinic keratosis does not affect
      peripheral regulatory T-cell level or function.

PMID- 25847123
TI  - SirT1 and STAT3 protect retinal pigmented epithelium cells against oxidative
      stress.
AB  - It has been previously demonstrated that there are interactions between sirtuin 1
      (SirT1) and signal transducer and activator of transcription 3 (STAT3), which
      have versatile roles in various microenvironments. However, whether or not there
      is crosstalk between these two molecules during oxidative stress, and what
      mechanism of crosstalk occurs in retinal pigmented epithelium cells (RPEs), the
      protection of which may delay the process of age-related macular degeneration
      (AMD), has required further elucidation. The present study aimed to investigate
      the interactions between SirT1 and STAT3 in RPEs, following exposure to oxidative
      stress. The rates of proliferation and apoptosis, levels of intracellular
      reactive oxygen species and cell senescence of RPEs, induced by oxidants [H2O2
      and oxidized low density lipoprotein (oxLDL)], were evaluated. The results
      revealed a downregulation of SirT1 expression, and an upregulation of STAT3
      expression during oxidative stress. Further investigation indicated that SirT1
      protected RPEs from oxidative stress-induced damage. Furthermore, gain- and loss
      of-function experiments indicated that SirT1 had negative effects on the
      regulation of STAT3 expression in RPEs during oxidative stress. Notably, STAT3
      directly protected the cells from oxidative stress, rather than depending on
      SirT1. Additionally, the protective effects of STAT3 had no association with the
      modulation of cell senescence during oxidative stress. In conclusion, SirT1 had
      negative effects on the regulation of STAT3 expression during oxidative stress.
      However, SirT1 and STAT3 demonstrated protective roles against oxidative stress
      in RPEs. These results therefore suggested that there was an equilibrium
      mechanism between SirT1 and STAT3 against oxidative stress, meaning that an
      equilibrium mechanism is required to be considered when combined application of
      STAT3 and SirT1 were performed to treat AMD.

PMID- 25847124
TI  - A poly(lactide-co-glycolide) film loaded with abundant bone morphogenetic protein
      2: A substrate-promoting osteoblast attachment, proliferation, and
      differentiation in bone tissue engineering.
AB  - We explored a novel biodegradable poly(lactide-co-glycolide) (PLGA) film loaded
      with over 80 wt % bone morphogenetic protein (BMP)-2, which was regarded as a
      substrate-promoting osteoblast attachment, proliferation, and differentiation for
      application of bone tissue engineering. Using phospholipid as a surfactant, BMP-2
      was modified as a complex (PBC) for dispersing in PLGA/dichloromethane solution.
      The PLGA film loaded with BMP-2 and phospholipid complex (PBC-PF) showed rough
      and draped morphology with high entrapment efficiency exceeding 80% and good
      hydrophilicity, respectively. The in vitro release study of BMP-2 showed that
      about 50% BMP-2 was slowly and continuously released from PBC-PF within 5 weeks
      and had a short initial burst release only in the last 1.5 days, which was better
      than serious burst release of PLGA film loaded with pure BMP-2 without
      phospholipid (BMP-PF) as control. By comparison with other PLGA films and tissue
      culture plates, it was confirmed that PBC-PF significantly promoted the
      attachment, proliferation, and differentiation of osteoblasts with higher
      entrapment efficiency and better sustained release. These advantages illustrated
      that PBC-PF could be a potential substrate providing long-term requisite growth
      factors for osteoblasts, which might be applied in bone tissue engineering.

PMID- 25847125
TI  - DNA damage and S phase arrest induced by Ochratoxin A in human embryonic kidney
      cells (HEK 293).
AB  - Ochratoxin A (OTA) is a ubiquitous mycotoxin with potential nephrotoxic,
      hepatotoxic and immunotoxic effects. The mechanisms underlying the nephrotoxicity
      of OTA remain obscure. To investigate DNA damage and the changes of the cell
      cycle distribution induced by OTA, human embryonic kidney cells (HEK 293 cells)
      were incubated with various concentrations of OTA for 24h in vitro. The results
      indicated that OTA treatment led to the production of reactive oxygen species
      (ROS) and to a decrease of the mitochondrial membrane potential (DeltaPsim). OTA
      induced DNA damage in HEK 293 cells was evidenced by DNA comet tails formation
      and increased expression of gamma-H2AX. In addition, OTA could induce cell cycle
      arrest at the S phase in HEK 293 cells. The expression of key cell cycle
      regulatory factors that were critical to the S phase, including cyclin A2, cyclin
      E1, and CDK2, were further detected. The expression of cyclin A2, cyclin E1, and
      CDK2 were significantly decreased by OTA treatment at both the mRNA and protein
      levels. The apoptosis of HEK 293 cells after OTA treatment was observed using
      Hoechst 33342 staining. The results confirmed that OTA did induce apoptosis in
      HEK 293 cells. In conclusion, our results provided new insights into the
      molecular mechanisms by which OTA might promote nephrotoxicity. 

PMID- 25847126
TI  - Multi-functional ion-sensor based on a photochromic diarylethene with a 1H
      imidazo [4,5-f][1,10] phenanthroline unit.
AB  - A new asymmetrical diarylethene containing a 1H-imidazo [4,5-f][1,10]
      phenanthroline unit was synthesized. The compound showed typical photochromism
      and functioned as a notable fluorescence switch upon alternating irradiation with
      ultraviolet (UV) and visible light. Its closed-ring isomer could be used as a
      selective 'naked-eye' colorimetric sensor for Cu(2+), accompanied by a notable
      color change from blue to colorless. Furthermore, the compound was found to be
      selective towards Ca(2+), Mg(2+), and Sr(2+) with significant fluorescence
      changes. On the basis of this characteristic, a logic circuit was constructed by
      utilizing both light and chemical stimuli as inputs and fluorescence intensity at
      487 nm as output.

PMID- 25847127
TI  - Magnetic controlling of migration of DNA and proteins using one-step modified
      gold nanoparticles.
AB  - A protocol was developed for preparing magnetic gold nanoparticles via one-step
      modification with a paramagnetic cationic surfactant. These magnetic gold
      nanoparticles can bind to and manipulate a low strength magnetic field-based
      delivery of DNA and proteins powerfully and non-invasively. 

PMID- 25847128
TI  - Detection and partial characterization of antifungal bioactivity from the
      secretions of the medicinal maggot, Lucilia sericata.
AB  - The antibacterial properties of the excretions/secretions (ES) of the medicinal
      maggot, Lucilia sericata have long been known and the effectiveness of maggot
      debridement therapy in relation to the clearance of bacteria from the surface of
      wounds has been the source of much research over recent years. Less well known,
      however, are the antifungal properties of L. sericata ES. Here, we show by means
      of the colony forming unit assay and optical density assays, that L. sericata
      native ES possess significant antifungal properties and appears to possess a
      highly heat stable, freeze/thaw, and lyophilization resistant antifungal
      component. We also show that the antifungal activity present in the native ES
      consists of a number of antifungal components present in three fraction masses
      consisting of >10, 10-0.5, and <0.5 kDa, with the greatest level of activity
      being seen in the <0.5 kDa fraction. 

PMID- 25847129
TI  - Cyclone performances depend on multiple factors: comments on "A CFD study of the
      effect of cyclone size on its performance parameters" by Mehdi Azadi et al.
      (2010).

PMID- 25847131
TI  - Intrapleural alteplase decreases parapneumonic effusion volume in children more
      than saline irrigation.
AB  - OBJECTIVE: In this prospective, double-blind, randomized crossover trial, we
      determined the effect of intrapleural fibrinolysis with alteplase compared to
      that of normal saline irrigation on the thoracostomy tube output and pleural
      effusion volume in children with complicated parapneumonic effusion. METHODS:
      Twenty seven children, median age 3.5 years, referred to the interventional
      radiology service for thoracostomy tube drainage of a parapneumonic effusion were
      studied. Seventeen patients with pleural fluid thickness greater than 2 cm or
      >20% ipsilateral chest volume after 8 hr of thoracostomy tube drainage entered
      the treatment arm. They were randomized to receive alteplase 0.1 mg/kg twice a
      day on days 1 and 3, or on days 2 and 4, with normal saline irrigation on the
      alternate days. Daily pleural fluid volume measured by low dose chest computed
      tomography (CT) and thoracostomy tube output was compared between the saline and
      alteplase groups. RESULTS: Compared to normal saline irrigation, alteplase
      irrigation resulted in increased thoracostomy tube drainage and to a greater
      decline in pleural fluid volume. Earlier alteplase administration resulted in
      increased fluid mobilization compared to administration later in the hospital
      course. There were no bleeding complications. CONCLUSIONS: Intrapleural
      fibrinolysis with alteplase safely increases pleural drainage and decreases the
      volume of pleural inflammatory debris compared to intrapleural administration of
      normal saline. The benefit of intrapleural alteplase on decreasing the volume of
      pleural inflammatory debris occurs for up to 72 hr with repeated twice daily
      dosing.

PMID- 25847130
TI  - Pre-transplant antibody screening and anti-CD154 costimulation blockade promote
      long-term xenograft survival in a pig-to-primate kidney transplant model.
AB  - Xenotransplantation has the potential to alleviate the organ shortage that
      prevents many patients with end-stage renal disease from enjoying the benefits of
      kidney transplantation. Despite significant advances in other models, pig-to
      primate kidney xenotransplantation has met limited success. Preformed anti-pig
      antibodies are an important component of the xenogeneic immune response. To
      address this, we screened a cohort of 34 rhesus macaques for anti-pig antibody
      levels. We then selected animals with both low and high titers of anti-pig
      antibodies to proceed with kidney transplant from galactose-alpha1,3-galactose
      knockout/CD55 transgenic pig donors. All animals received T-cell depletion
      followed by maintenance therapy with costimulation blockade (either anti-CD154
      mAb or belatacept), mycophenolate mofetil, and steroid. The animal with the high
      titer of anti-pig antibody rejected the kidney xenograft within the first week.
      Low-titer animals treated with anti-CD154 antibody, but not belatacept exhibited
      prolonged kidney xenograft survival (>133 and >126 vs. 14 and 21 days,
      respectively). Long-term surviving animals treated with the anti-CD154-based
      regimen continue to have normal kidney function and preserved renal architecture
      without evidence of rejection on biopsies sampled at day 100. This description of
      the longest reported survival of pig-to-non-human primate kidney
      xenotransplantation, now >125 days, provides promise for further study and
      potential clinical translation. 

PMID- 25847132
TI  - The problem of publication-pollution denialism.

PMID- 25847134
TI  - Azadirachtin, a neem-derived biopesticide, impairs behavioral and hematological
      parameters in carp (Cyprinus carpio).
AB  - Azadirachtin (Aza) is a promisor biopesticide used in organic production and
      aquaculture. Although this compound is apparently safe, there is evidence that it
      may have deleterious effects on fish. Behavioral and hematological tests are
      grouped into a set of parameters that may predict potential toxicity of chemical
      compounds. Here, we investigate the effects of Aza, in the commercial formulation
      NeenmaxTM , on carp (Cyprinus carpio) by defining LC50 (96 h), and testing
      behavioral and hematological parameters. In our study, LC50 was estimated at 80
      MUL/L. We exposed carp to Aza at 20, 40, and 60 MUL/L, values based on 25, 50,
      and 75% of LC50 , respectively. At 60 MUL/L, Aza promoted significant changes in
      several parameters, increasing the distance traveled and absolute turn angle. In
      addition, the same concentration decreased the time spent immobile and the number
      of immobile episodes. Hematological parameters, such as hematocrit, hemoglobin,
      hematimetrics index, and red cell distribution, were decreased at 60 MUL/L Aza
      exposure. In conclusion, our study demonstrates that 60 MUL/L Aza altered
      locomotor activity, motor pattern, and hematological parameters, suggesting
      potential toxicity to carp after acute exposure. In addition, this is the first
      report that evaluates the actions of a chemical contaminant using automated
      behavioral tracking of carp, which may be a useful tool for assessing the
      potential toxicity of biopesticides in conjunction with hematological tests. (c)
      2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1381-1388, 2016.

PMID- 25847133
TI  - RNA pol II transcript abundance controls condensin accumulation at mitotically up
      regulated and heat-shock-inducible genes in fission yeast.
AB  - Condensin plays fundamental roles in chromosome dynamics. In this study, we
      determined the binding sites of condensin on fission yeast (Schizosaccharomyces
      pombe) chromosomes at the level of nucleotide sequences using chromatin
      immunoprecipitation (ChIP) and ChIP sequencing (ChIP-seq). We found that
      condensin binds to RNA polymerase I-, II- and III-transcribed genes during both
      mitosis and interphase, and we focused on pol II constitutive and inducible
      genes. Accumulation sites for condensin are distinct from those of cohesin and
      DNA topoisomerase II. Using cell cycle stage and heat-shock-inducible genes, we
      show that pol II-mediated transcripts cause condensin accumulation. First,
      condensin's enrichment on mitotically activated genes was abolished by deleting
      the sep1(+) gene that encodes an M-phase-specific forkhead transcription factor.
      Second, by raising the temperature, condensin accumulation was rapidly induced at
      heat-shock protein genes in interphase and even during mid-mitosis. In
      interphase, condensin accumulates preferentially during the postreplicative
      phase. Pol II-mediated transcription was neither repressed nor activated by
      condensin, as levels of transcripts per se did not change when mutant condensin
      failed to associate with chromosomal DNA. However, massive chromosome
      missegregation occurred, suggesting that abundant pol II transcription may
      require active condensin before proper chromosome segregation. 

PMID- 25847135
TI  - Maintenance of distinct melanocyte populations in the interfollicular epidermis.
AB  - Hair follicles and sweat glands are recognized as reservoirs of melanocyte stem
      cells (MSCs). Unlike differentiated melanocytes, undifferentiated MSCs do not
      produce melanin. They serve as a source of differentiated melanocytes for the
      hair follicle and contribute to the interfollicular epidermis upon wounding,
      exposure to ultraviolet irradiation or in remission from vitiligo, where
      repigmentation often spreads outwards from the hair follicles. It is unknown
      whether these observations reflect the normal homoeostatic mechanism of
      melanocyte renewal or whether unperturbed interfollicular epidermis can maintain
      a melanocyte population that is independent of the skin's appendages. Here, we
      show that mouse tail skin lacking appendages does maintain a stable melanocyte
      number, including a low frequency of amelanotic melanocytes, into adult life.
      Furthermore, we show that actively cycling differentiated melanocytes are present
      in postnatal skin, indicating that amelanotic melanocytes are not uniquely relied
      on for melanocyte homoeostasis. 

PMID- 25847136
TI  - Minimally invasive treatment of traumatic high rectovaginal fistulas.
AB  - BACKGROUND: We propose a new minimally invasive technique by laparoscopic
      approach which minimizes parietal damage and allows precise location of the
      fistula, hence reduces blind dissection. METHODS: Ten consecutive patients
      suffering from a HRVF benefited from the described technique. Location and time
      frame were east of the Democratic Republic of Congo and September 2012 through
      January 2014. By laparoscopy, dissection of the mesorectum in the "holy plane" is
      taken posteriorly as distally on the sacrum as possible. Dissection subsequently
      continues laterally beyond the fistula in an effort to maximally circumvene the
      fistulous area where no plane of cleavage can be found. If the cleavage plane
      beyond the fistula addresses a healthy rectum, a suture of vaginal and rectal
      defect is performed. If the cleavage plane beyond the fistula involves
      significant laceration of the rectum, while leaving at least 2 cm of healthy
      rectum above the sphincter, rectal resection and colorectal anastomosis are
      performed. If the rectal laceration involves the distal 2 cm but halts short of
      the sphincter (large fistula), the pull-through technique is performed. RESULTS:
      Of ten participants, four had large HRVF and two presented significant fibrosis.
      Three underwent simple suture of rectal and vaginal defect, one rectal resection
      and six a "pull-through" technique. The median procedure time was 1h50 (1h00
      3h30). There was no morbidity. None of the patients required protective ileostomy
      or colostomy. Nine patients were declared clinically cured with a median follow
      up of 14.3 months (11-36). The Cleveland Clinic Incontinence Score was 20 in all
      patients before the treatment and was significantly (p = 0.004) reduced to 2.6 [0
      20] after the treatment. CONCLUSIONS: This minimally invasive technique allowed
      us to treat HRVF, including complex ones in ten patients without significant
      morbidity. Clinical success with a median follow-up of 14.3 months was 90%.

PMID- 25847137
TI  - A utility of peroral endoscopic myotomy (POEM) across the spectrum of esophageal
      motility disorders.
AB  - BACKGROUND: Peroral endoscopic myotomy (POEM) has been performed as a novel
      endoscopic procedure to treat achalasia with favorable outcome. The objective of
      this study was to assess the outcome of POEM in our initial series and to assess
      the safety and efficacy of POEM in a variety of esophageal motility-related
      clinical problems. METHODS: This is a retrospective cross-sectional study
      involving all patients with esophageal motility disorders defined by the Chicago
      classification, who had undergone consideration for POEM at our institution.
      Validated questionnaires such as gastroesophageal reflux disease health-related
      quality of life (GERD-HRQL), reflux symptom index (RSI) and achalasia disease
      specific health-related quality of life were obtained pre- and postoperatively.
      RESULTS: From January 2013 to October 2014, a total of 35 POEMs (achalasia n =
      25, non-achalasia n = 10) were performed on 33 patients (female n = 20, male n =
      13, mean age 56.9 years). There was no mortality. The rate of inadvertent
      mucosotomy was 17.1%. The rate of complications requiring interventions was 5.7%.
      During a mean follow-up period of 7 months (range 0.5-17), 92% of patients with
      achalasia and 75% of those with non-achalasia motility disorders had a
      symptomatic improvement in dysphagia. Chest pain was completely resolved in all
      patients with achalasia (8/8) and 80% of patients with non-achalasia (4/5). The
      GERD-HRQL, RSI and dysphagia scores significantly improved after POEM in patients
      with achalasia. There was a significant improvement in GERD-HRQL and RSI scores,
      and a trend toward lower dysphagia score in patients with non-achalasia.
      CONCLUSIONS: The outcome of POEM to treat achalasia and non-achalasia motility
      disorders is consistent with previous studies. Potential benefit of POEM includes
      not only its flexibility to adjust the length and location of myotomy but also
      the ability to extend myotomy proximally without thoracoscopy or thoracotomy.
      POEM can be combined with laparoscopic procedures and used as "salvage" for
      localized esophageal dysmotility.

PMID- 25847138
TI  - Patients with psychiatric comorbidity can safely undergo bariatric surgery with
      equivalent success.
AB  - INTRODUCTION: Patients with psychiatric disorder were reported to have a poor
      outcome in bariatric surgery. Few studies have examined the outcome of
      laparoscopic sleeve gastrectomy (LSG) and laparoscopic adjustable gastric banding
      (LAGB) in patients with psychiatric history. We aimed to compare excess weight
      loss (%EWL) in patients with and without psychiatric comorbidities who underwent
      LSG or LAGB. METHODS: Patients undergoing LSG or LAGB were identified from our
      prospective database. A multidisciplinary team evaluated all patients
      preoperatively, including a psychological evaluation. Patients with the diagnosis
      of depression, anxiety, bipolar disorder, and schizophrenia were included in the
      psychiatric comorbidity group (PSY). Others were included in group NON-PSY. All
      patients were first screened to be psychologically stable to undergo surgery.
      Initial BMI and %EWL at 3, 6, and 12 months postoperatively were compared.
      RESULTS: A total of 590 patients (81.4 % women), with a median BMI of 43.8
      kg/m(2) (range 30-99) who underwent LSG (n = 222) or LAGB (n = 368) from January
      2006 to June 2013, were identified. Psychiatric comorbidities that were well
      controlled at the time of surgery were found in 188 patients (31.9%). Diagnostic
      criteria for depression were met in 154 patients (26.1%), 75 patients suffered
      from anxiety (12.7%), 9 from bipolar disorder, and 4 from schizophrenia (0.7%).
      Initial BMI was not different between the two groups. No significant difference
      in %EWL between the groups was found during follow-up (44.13 vs. 43.37%EWL,
      respectively, at 1 year; p = 0.76). When LSG and LAGB patients were analyzed as
      subsets, again no difference in %EWL at 1 year was found for PSY vs. NON-PSY
      (LSG: 51.56 vs. 54.86%EWL; LAGB: 38.48 vs. 38.45%EWL, all p = ns). In
      multivariate analysis, the differences from unadjusted analysis persisted.
      CONCLUSION: These findings demonstrate that a similar %EWL can be achieved in
      patients undergoing LSG or LAGB despite the presence of well-controlled
      psychiatric comorbidity.

PMID- 25847139
TI  - Robotic versus laparoscopic surgery for colonic disease: a meta-analysis of
      postoperative variables.
AB  - INTRODUCTION: An increasing number of studies have been published since the
      introduction of robotic technology into general surgery. Gastrointestinal surgery
      is an area of special interest for the robotic surgeon. Colonic surgery can be
      challenging depending on the disease and the operative approach. We seek to
      perform a meta-analysis comparing robotic surgery against laparoscopic surgery in
      this particular field. MATERIALS AND METHODS: We performed a systematic search of
      MEDLINE database from January 2001 to July 2013 supplemented by manual searches
      of bibliographies of key relevant articles. Randomized controlled trials and
      cohort studies were selected for review and for collection of postoperative data
      (length of stay, time to first flatus and complications). RESULTS: After careful
      review, nine studies were considered for analysis. Non-pooled data showed a
      slight trend toward laparoscopy with increased number of events without
      statistical significance. Pooled data demonstrated a statistical significance for
      return to bowel function in the right and mixed robotic colectomy arm (WSMD 
      0.33, 95 % CI -0.5, -0.1; p < 0.005 and WSMD -0.26, 95 % CI -0.51, 0.0; p =
      0.05). Pooled data of length of stay and complications showed no statistical
      significance between robotic and laparoscopic colonic surgery. DISCUSSION:
      Robotic surgery is a comparable option when dealing with colonic disease, either
      benign or malignant. No difference in complication rate or length of stay was
      found when comparing the two. Robotic surgery appears to have an advantage over
      laparoscopy in regards to return of bowel function when dealing with right
      colectomies.

PMID- 25847140
TI  - Age-related sensitivity to endotoxin-induced liver inflammation: Implication of
      inflammasome/IL-1beta for steatohepatitis.
AB  - Aging is associated with increased vulnerability to inflammatory challenge.
      However, the effects of altered inflammatory response on the metabolic status of
      tissues or organs are not well documented. In this study, we present evidence
      demonstrating that lipopolysaccharide (LPS)-induced upregulation of the
      inflammasome/IL-1beta pathway is accompanied with an increased inflammatory
      response and abnormal lipid accumulation in livers of aged rats. To monitor the
      effects of aging on LPS-induced inflammation, we administered LPS (2 mg kg(-1) )
      to young (6-month old) and aged (24-month old) rats and found abnormal lipid
      metabolism in only aged rats with increased lipid accumulation in the liver. This
      lipid accumulation in the liver was due to the dysregulation of PPARalpha and
      SREBP1c. We also observed severe liver inflammation in aged rats as indicated by
      increased ALT levels in serum and increased Kupffer cells in the liver.
      Importantly, among many inflammation-associated factors, the aged rat liver
      showed chronically increased IL-1beta production. Increased levels of IL-1beta
      were caused by the upregulation of caspase-1 activity and inflammasome
      activation. In vitro studies with HepG2 cells demonstrated that treatment with IL
      1beta significantly induced lipid accumulation in hepatocytes through the
      regulation of PPARalpha and SREBP1c. In summary, we demonstrated that LPS-induced
      liver inflammation and lipid accumulation were associated with a chronically
      overactive inflammasome/IL-1beta pathway in aged rat livers. Based on the present
      findings, we propose a mechanism of aging-associated progression of
      steatohepatitis induced by endotoxin, delineating a pathogenic role of the
      inflammasome/IL-1beta pathway involved in lipid accumulation in the liver.

PMID- 25847141
TI  - Telomerase reverse transcriptase promoter methylation is related to a risk of
      recurrence in hepatocellular carcinoma.

PMID- 25847142
TI  - Autophagic adaptation is associated with exercise-induced fibre-type shifting in
      skeletal muscle.
AB  - AIM: Acute exercise is known to activate autophagy in skeletal muscle. However,
      little is known about how basal autophagy in skeletal muscle adapts to chronic
      exercise. In the current study we aim to, firstly, examine whether long-term
      habitual exercise alters the basal autophagic signalling in plantaris muscle and,
      secondly, examine the association between autophagy and fibre-type shifting.
      METHODS: Adult female Sprague-Dawley rats aged 2 months were randomly assigned to
      control and exercise groups. Animals in exercise group were kept in cages
      equipped with free access running wheels to perform habitual exercise for 5
      months. Animals in the control group were caged in the absence of running wheels.
      Animals were sacrificed after the 5-month experimental period. Plantaris muscle
      tissues were harvested for analysis. RESULTS: We showed that long-term habitual
      exercise enhanced basal autophagy, but without altering expressions of autophagy
      proteins in plantaris muscle. Interestingly, sirtuin protein, a possible
      regulator of autophagy, was upregulated in plantaris muscle. Furthermore, we
      suspected that different types of muscle fibre adapted to chronic exercise in
      different ways. Long-term habitual exercise resulted in fibre-type shifting from
      type IIX to IIA in both gastrocnemius muscle and plantaris muscle. Intriguingly,
      our analysis demonstrated that LC3-II protein abundance is positively correlated
      with the proportion of type IIA fibre whereas it was negatively correlated with
      the proportion of type IIX fibre in plantaris muscle. PGC-1alpha protein
      abundance was positively associated with the proportion of type IIA fibre and LC3
      II in plantaris muscle. CONCLUSION: These results suggest that basal autophagy is
      enhanced in plantaris muscle after long-term habitual exercise and associated
      with fibre-type shifting.

PMID- 25847143
TI  - Analysis of signal processing in vestibular circuits with a novel light-emitting
      diodes-based fluorescence microscope.
AB  - Optical visualization of neural network activity is limited by imaging system
      dependent technical tradeoffs. To overcome these constraints, we have developed a
      powerful low-cost and flexible imaging system with high spectral variability and
      unique spatio-temporal precision for simultaneous optical recording and
      manipulation of neural activity of large cell groups. The system comprises eight
      high-power light-emitting diodes, a camera with a large metal-oxide-semiconductor
      sensor and a high numerical aperture water-dipping objective. It allows fast and
      precise control of excitation and simultaneous low noise imaging at high
      resolution. Adjustable apertures generated two independent areas of variable size
      and position for simultaneous optical activation and image capture. The
      experimental applicability of this system was explored in semi-isolated
      preparations of larval axolotl (Ambystoma mexicanum) with intact inner ear organs
      and central nervous circuits. Cyclic galvanic stimulation of semicircular canals
      together with glutamate- and gamma-aminobutyric acid (GABA)-uncaging caused a
      corresponding modulation of Ca(2+) transients in central vestibular neurons.
      These experiments revealed specific cellular properties as well as synaptic
      interactions between excitatory and inhibitory inputs, responsible for spatio
      temporal-specific sensory signal processing. Location-specific GABA-uncaging
      revealed a potent inhibitory shunt of vestibular nerve afferent input in the
      predominating population of tonic vestibular neurons, indicating a considerable
      impact of local and commissural inhibitory circuits on the processing of
      head/body motion-related signals. The discovery of these previously unknown
      properties of vestibular computations demonstrates the merits of our novel
      microscope system for experimental applications in the field of neurobiology. 

PMID- 25847144
TI  - Association between the expression of T-cadherin and vascular endothelial growth
      factor and the prognosis of patients with gastric cancer.
AB  - T-cadherin has been identified as a tumor-suppressor gene in several types of
      cancer. The present study aimed to investigate the association of the expression
      of T-cadherin with angiogenesis, and to evaluate its prognostic value for
      patients with primary gastric cancer. Gastric cancer tissues and matched adjacent
      tissues from 166 patients receiving surgical resection were included in the
      present study. The expression of T-cadherin was detected using
      immunohistochemistry, western blotting and reverse transcription-quantitative
      polymerase chain reaction. The expression of vascular epidermal growth factor
      (VEGF) was detected using immunohistochemistry, and its association with the
      expression of T-cadherin was analyzed. In addition, the association between the
      expression of T-cadherin and clinicopathological features were analyzed. The mRNA
      and protein expression levels of T-cadherin were significantly lower in the
      gastric cancer tissue compared with the corresponding adjacent normal tissue
      (P<0.05). The expression of VEGF was not associated with the expression of T
      cadherin in the gastric cancer tissue. The decreased protein expression of T
      cadherin correlated with smoking, larger tumor size (diameter, >4 cm), lymph node
      metastasis and a higher tumor-lymph node-metastasis stage (P<0.05 or P<0.01).
      However, the expression of T-cadherin was not correlated with gender, age,
      alcohol intake, Helecobacter pylori infection or differentiation (P>0.05). The
      multivariate analysis demonstrated that the expression of T-cadherin was an
      independent prognostic factor for the overall survival rate of patients with
      gastric cancer. This data suggested that the downregulation of T-cadherin may
      contribute to gastric cancer progression, representing a useful biomarker for
      predicting the biological behavior and prognosis of gastric cancer. However, no
      significant association was observed between the expression of VEGF and T
      cadherin.

PMID- 25847145
TI  - Evolution of cooperation in a multidimensional phenotype space.
AB  - The emergence of cooperation in populations of selfish individuals is a
      fascinating topic that has inspired much theoretical work. An important model to
      study cooperation is the phenotypic model, where individuals are characterized by
      phenotypic properties that are visible to others. The phenotype of an individual
      can be represented for instance by a vector x = (x1,...,xn), where x1,...,xn are
      integers. The population can be well mixed in the sense that everyone is equally
      likely to interact with everyone else, but the behavioral strategies of the
      individuals can depend on their distance in the phenotype space. A cooperator can
      choose to help other individuals exhibiting the same phenotype and defects
      otherwise. Cooperation is said to be favored by selection if it is more abundant
      than defection in the stationary state. This means that the average frequency of
      cooperators in the stationary state strictly exceeds 1/2. Antal et al. (2009c)
      found conditions that ensure that cooperation is more abundant than defection in
      a one-dimensional (i.e. n = 1) and an infinite-dimensional (i.e. n = infinity)
      phenotype space in the case of the Prisoner's Dilemma under weak selection.
      However, reality lies between these two limit cases. In this paper, we derive the
      corresponding condition in the case of a phenotype space of any finite dimension.
      This is done by applying a perturbation method to study a mutation-selection
      equilibrium under weak selection. This condition is obtained in the limit of a
      large population size by using the ancestral process. The best scenario for
      cooperation to be more likely to evolve is found to be a high population-scaled
      phenotype mutation rate, a low population-scaled strategy mutation rate and a
      high phenotype space dimension. The biological intuition is that a high
      population-scaled phenotype mutation rate reduces the quantity of interactions
      between cooperators and defectors, while a high population-scaled strategy
      mutation rate introduces newly mutated defectors that invade groups of
      cooperators. Finally it is easier for cooperation to evolve in a phenotype space
      of higher dimension because it becomes more difficult for a defector to migrate
      to a group of cooperators. The difference is significant from n = 1 to n = 2 and
      from n = 2 to n = 3, but becomes small as soon as n >= 3.

PMID- 25847146
TI  - Posttonsillectomy weight loss in adults.
AB  - OBJECTIVE: To analyze and determine the incidence and severity of weight loss in
      adult tonsillectomies. STUDY DESIGN: Case series with chart review. SETTING:
      Adult tonsillectomy is performed for a variety of indications. Anecdotally,
      patients report a 10- to 15-pound weight loss in the postoperative period;
      however, no supporting research has been documented. The pediatric population has
      a well-documented weight gain postoperatively. SUBJECTS: In total, 138 adults
      (aged 18-40 years) receiving tonsillectomy at Naval Medical Center Portsmouth
      (NMCP) between 2008 and 2013. METHODS: A retrospective study was performed using
      an S3 surgery scheduling system search of all adult tonsillectomies at NMCP
      between 2008 and 2013. A subsequent electronic medical record search (AHLTA) of
      preoperative and postoperative weights and demographics was performed. RESULTS:
      Data analysis revealed a significant difference found between preoperative and
      postoperative weight across all age groups (4.77 pounds, P < .005). Analysis of
      variance was performed to determine if there is a significant difference between
      these age and body mass index (BMI) groups. The highest amount of weight loss was
      observed in the oldest population group (5.72 pounds in subjects aged >40 years,
      4.95 pounds in 31- to 40-year-olds, and 5.44 pounds in 20- to 30-year-olds, P =
      .03). Age comparisons were statistically significant. There was no statistically
      significant association between BMI and postoperative weight loss. CONCLUSIONS:
      These results indicate that there is evidence of a roughly 5-pound weight loss in
      the postoperative period following tonsillectomy in adults with subsequent return
      to baseline weight after roughly 5 months. These findings are significant since
      this could lead to further research into changes in obesity-associated disease.

PMID- 25847147
TI  - Parathyroid Localization and Preservation during Transcervical Resection of
      Substernal Thyroid Glands.
AB  - OBJECTIVE: The feasibility of parathyroid preservation during thyroidectomy has
      not been well documented for cases in which the thyroid gland extends into the
      mediastinum. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary academic
      referral center. SUBJECTS AND METHODS: In this retrospective cohort study, 70
      consecutive patients who had substernal thyroid glands treated with a
      transcervical thyroidectomy between 1993 and 2013 were compared with 286
      thyroidectomies that did not entail substernal extension within that same time
      period. All localized parathyroid glands were confirmed histologically. RESULTS:
      Of 160 possible parathyroid glands in the substernal cases, 119 (74%) were
      histologically confirmed intraoperatively (67 superior and 52 inferior). In
      nonsubsternal cases, 725 (89%) were histologically confirmed (372 superior and
      353 inferior). There was a statistically significant difference between the
      substernal and nonsubsternal cases in the total number of glands found (P <
      .0001) and the number of superior and inferior glands that were identified (P =
      .009 and < 0.0001). CONCLUSIONS: Even when the thyroid gland extends into the
      mediastinum, it is often possible, although with reduced efficiency, to identify
      and preserve the parathyroid glands.

PMID- 25847148
TI  - Reliability and accuracy of simple visual estimation in assessment of peripheral
      arterial stenosis.
AB  - PURPOSE: To evaluate reliability, accuracy, and agreement of simple visual
      estimation (SVE) in determining the degree of peripheral arterial stenosis
      compared with calibrated measurements. MATERIALS AND METHODS: In 2 sessions, 23
      interventionists with a wide range of experience and subspecialty training
      reviewed 42 angiographic images of lower extremity and carotid arteries (21
      iliofemoral arteries and 21 carotid arteries). An independent physician measured
      all lesions using manual calipers. Intrarater and interrater reliability were
      assessed by intraclass correlation. A +/- 5% error was considered the threshold
      for accuracy, and weighted kappa statistics were computed to assess agreement
      with respect to the degree of stenosis (< 50%, nonsignificant; 50%-80%,
      significant; > 80%, severe). RESULTS: Intrarater reliability of SVE was 0.99, and
      interrater reliability was 0.83. Accuracy varied from 52.8% for images of severe
      stenosis to 26.5% and 18.1% for significant and nonsignificant stenosis,
      respectively (P < .001). Agreement between SVE and caliper with regard to degree
      of stenosis was good (weighted kappa 0.56) overall with correct classification
      ranging from 92.6% for severe stenosis to 53.4% and 68.2% for significant and
      nonsignificant stenosis, respectively (P < .001). Misclassification of
      nonsignificant and significant stenosis was more frequent for carotid arteries
      than for lower extremities. CONCLUSIONS: Despite high reliability, SVE of
      peripheral arterial stenosis has limited accuracy in determining the exact degree
      of stenosis. Although severe stenosis is readily identified by SVE, arterial
      stenosis of < 80% is frequently overestimated, especially for carotid arteries,
      and should be confirmed by caliper assessment.

PMID- 25847149
TI  - Endovenous Laser Ablation of Perforating Veins: Feasibility, Safety, and
      Occlusion Rate Using a 1,470-nm Laser and Bare-Tip Fiber.
AB  - PURPOSE: To describe technical feasibility and safety of perforating vein
      ablation with the use of a 1,470-nm laser and bare-tip fiber in the management of
      chronic venous insufficiency (CVI). MATERIALS AND METHODS: A total of 171
      perforating veins were ablated in 101 limbs of 87 patients (mean age, 54.4 y; 79%
      female). Outcomes included sonographic occlusion of ablated perforator,
      subjective changes of insufficiency symptoms, incidence of procedure-related side
      effects (pain, hyperpigmentation), and complications (burn, infection, deep vein
      thrombosis, paresthesia). Correlation between perforator closure and patient
      symptoms was assessed by Pearson chi(2) test. Factors influencing failure of
      perforator closure were analyzed by analysis of variance. RESULTS: Forty-nine
      perforating veins had previous great saphenous vein (GSV) interruption, 25 had
      previous small saphenous vein (SSV) interruption, 88 had previous GSV and SSV
      interruption, and 9 had competent saphenous systems. Ninety-one ablations were
      combined with microphlebectomy, 55 were combined with sclerotherapy, and 25 were
      performed alone. At 1 and 3 months' follow-up, 94% and 98% of ablated perforators
      were sonographically occluded, and 82% and 96% of patients noted complete symptom
      resolution, respectively. Complications included 5 cases of new-onset paresthesia
      and 1 case of nonocclusive deep vein thrombosis. Ablation failed in 10
      perforators, and treatment failure showed significant correlations with higher
      clinical, etiology, anatomy, and physiology score (P = .002) and history of
      GSV/SSV interruption (P = .042). CONCLUSIONS: Three-month closure of perforating
      veins is achievable by using a 1,470-nm laser and bare-tip fiber and can be
      safely performed alone or in combination with microphlebectomy or sclerotherapy
      at all stages of CVI severity.

PMID- 25847150
TI  - Tumor necrosis factor-alpha is a potential diagnostic biomarker for chronic
      neuropathic pain after spinal cord injury.
AB  - Neuropathic pain (NP) is one of the most common complications after spinal cord
      injury (SCI), but no protein biomarkers has ever been introduced into clinical
      diagnosis. Previous studies implicated that toll-like receptor (TLR) 4 played a
      critical role in the development of NP in animal SCI models. Here, a total of 140
      participants were recruited, 70 of them were SCI-NP subject and the rest 70
      controls did not show neuropathic symptoms. TLR4 was upregulated significantly in
      SCI-NP patients compared with SCI-noNP subjects. Furthermore, we measured the
      concentrations of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL
      6), two TLR4 downstream pro-inflammatory cytokines, to assess their diagnostic
      values. Receiver operating characteristics (ROC) analysis revealed that TNF-alpha
      had great potential advantages to predict the progression of neuropathy, the
      risks of NP were strongly increased in SCI subjects with higher levels of TNF
      alpha (odds ratio: 4.92; 95% confidence interval: 1.89-12.32). These results
      suggested neuro-immune activation contributed to the development of neuropathic
      disorder after SCI, and TNF-alpha could be a potential sensitive diagnostic
      biomarker for chronic neuropathic pain in SCI patients. 

PMID- 25847151
TI  - Mitochondrial dynamics and inherited peripheral nerve diseases.
AB  - Peripheral nerves have peculiar energetic requirements because of considerable
      length of axons and therefore correct mitochondria functioning and distribution
      along nerves is fundamental. Mitochondrial dynamics refers to the continuous
      change in size, shape, and position of mitochondria within cells. Abnormalities
      of mitochondrial dynamics produced by mutations in proteins involved in
      mitochondrial fusion (mitofusin-2, MFN2), fission (ganglioside-induced
      differentiation-associated protein-1, GDAP1), and mitochondrial axonal transport
      usually present with a Charcot-Marie-Tooth disease (CMT) phenotype. MFN2
      mutations cause CMT type 2A by altering mitochondrial fusion and trafficking
      along the axonal microtubule system. CMT2A is an axonal autosomal dominant CMT
      type which in most cases is characterized by early onset and rather severe
      course. GDAP1 mutations also alter fission, fusion and transport of mitochondria
      and are associated either with recessive demyelinating (CMT4A) and axonal CMT (AR
      CMT2K) and, less commonly, with dominant, milder, axonal CMT (CMT2K). OPA1 (Optic
      Atrophy-1) is involved in fusion of mitochondrial inner membrane, and its
      heterozygous mutations lead to early-onset and progressive dominant optic atrophy
      which may be complicated by other neurological symptoms including peripheral
      neuropathy. Mutations in several proteins fundamental for the axonal transport or
      forming the axonal cytoskeleton result in peripheral neuropathy, i.e., CMT,
      distal hereditary motor neuropathy (dHMN) or hereditary sensory and autonomic
      neuropathy (HSAN), as well as in hereditary spastic paraplegia. Indeed,
      mitochondrial transport involves directly or indirectly components of the kinesin
      superfamily (KIF5A, KIF1A, KIF1B), responsible of anterograde transport, and of
      the dynein complex and related proteins (DYNC1H1, dynactin, dynamin-2),
      implicated in retrograde flow. Microtubules, neurofilaments, and chaperones such
      as heat shock proteins (HSPs) also have a fundamental role in mitochondrial
      transport and mutations in some of related encoding genes cause peripheral
      neuropathy (TUBB3, NEFL, HSPB1, HSPB8, HSPB3, DNAJB2). In this review, we address
      the abnormalities in mitochondrial dynamics and their role in determining CMT
      disease and related neuropathies. 

PMID- 25847152
TI  - Stochastic activation among inspiratory cells in the pre-Botzinger complex of the
      rat medulla revealed by Ca(2+) imaging.
AB  - In the pre-Botzinger complex of the ventral medulla (preBotC), a variable pattern
      of inspiratory neuronal output and synchronous activation of inspiratory cells
      can be observed. However, it is not well known whether cellular activation
      patterns among inspiratory cells are variable or fixed. Here, we evaluated the
      activation sequence of inspiratory cells during individual rhythmic bursts using
      calcium imaging. Onset timing and peak timing of calcium fluctuations during
      rhythmic bursts in individual inspiratory cells were used to evaluate the
      activation sequence. The sequences of both timings changed stochastically in
      individual rhythmic bursts, although the sequences differed between the two
      timings even within the same rhythmic burst. The weak correlation between these
      two timings might indicate that the two parameters reflect different
      physiological events. Furthermore, a subset of inspiratory cells was found to
      initially activate in the sequences of successive rhythmic bursts. These results
      suggest that rhythmic activation of inspiratory cells occurs with a degree of
      loose regularity but is not invariable with respect to the sequence of either
      onset or peak timing. 

PMID- 25847153
TI  - Downregulation of the microtubule associated protein tau impairs process
      outgrowth and myelin basic protein mRNA transport in oligodendrocytes.
AB  - Oligodendrocytes, the myelin forming cells of the CNS, are characterized by their
      numerous membranous extensions, which enwrap neuronal axons and form myelin
      sheaths. During differentiation oligodendrocytes pass different morphological
      stages, downregulate the expression of the proteoglycan NG2, and acquire major
      myelin specific proteins, such as myelin basic proteins (MBP) and proteolipid
      protein. MBP mRNA is transported in RNA granules along the microtubules (MTs) to
      the periphery and translated locally. MTs participate in the elaboration and
      stabilization of the myelin forming extensions and are essential for cellular
      sorting processes. Their dynamic properties are regulated by microtubule
      associated proteins (MAPs). The MAP tau is present in oligodendrocytes and
      involved in the regulation and stabilization of the MT network. To further
      elucidate the functional significance of tau in oligodendrocytes, we have
      downregulated tau by siRNA technology and studied the effects on cell
      differentiation and neuron-glia contact formation. The data show that tau
      knockdown impairs process outgrowth and leads to a decrease in MBP expression.
      Furthermore, MBP mRNA transport to distant cellular extensions is impaired and
      cells remain in the NG2 stage. In myelinating cocultures with dorsal root
      ganglion neurons, oligodendrocyte precursor cells after tau miR RNA lentiviral
      knockdown develop into NG2 positive cells with very long and thin processes,
      contacting axons loosely, but fail to form internodes. This demonstrates that tau
      is important for MBP mRNA transport and involved in process formation. The
      disturbance of the balance of tau leads to abnormalities in oligodendrocyte
      differentiation, neuron-glia contact formation and the early myelination process.

PMID- 25847155
TI  - Label-free colorimetric sensor for mercury(II) and DNA on the basis of
      mercury(II) switched-on the oxidase-mimicking activity of silver nanoclusters.
AB  - In this paper, a novel colorimetric biosensor for Hg(2+) and DNA molecules is
      presented based on Hg(2+) stimulated oxidase-like activity of bovine serum
      albumin protected silver clusters (BSA-Ag NCs). Under mild conditions, Hg(2+)
      activated BSA-Ag NCs to show high catalytic activity toward the oxidation of
      3,3',5, 5'-tetramethylbenzidine (TMB) using ambient dissolved oxygen as an
      oxidant. The oxidase-like activity of BSA-Ag NCs was "switched-on" selectively in
      the presence of Hg(2+), which permitted a novel and facile colorimetric sensor
      for Hg(2+). As low as 25 nmol L(-1)Hg(2+) could be detected with a linear range
      from 80 nmol L(-1) to 50 mmol L(-1). In addition, the sensing strategy was also
      employed to detect DNA molecules. Hg(2+) is known to bind very strongly and
      specifically with two DNA thymine bases (T) to form thymine-Hg(2+)-thymine (T
      Hg(2+)-T) base pairs. The hairpin-structure was disrupted and Hg(2+) ions were
      released after hybridization with the DNA target. By coupling the Hg(2+) switched
      on the oxidase-mimicking activity of BSA-Ag NCs, we developed a novel label-free
      strategy for facile and fast colorimetric detection of DNA molecules. More
      important, target DNA can be detected as low as 10 nmol L(-1) with a linear range
      from 30 to 225 nmol L(-1). Compared with other methods, this method presents
      several advantages such as the independence of hydrogen peroxide, high
      sensitivity and good selectivity, avoiding any modification or immobilization of
      DNA, which holds a great potential of metal NCs for clinical application in
      biosensing and biotechnology.

PMID- 25847156
TI  - Simultaneous determination of mercury and organic carbon in sediment and soils
      using a direct mercury analyzer based on thermal decomposition-atomic absorption
      spectrophotometry.
AB  - The purpose of this work was to study the feasibility of using a direct mercury
      analyzer (DMA) to simultaneously determine mercury (Hg) and organic matter
      content in sediment and soils. Organic carbon was estimated by re-weighing the
      sample boats post analysis to obtain loss-on-ignition (LOI) data. The DMA-LOI
      results were statistically similar (p<0.05) to the conventional muffle furnace
      approach. A regression equation was developed to convert DMA-LOI data to total
      organic carbon (TOC), which varied between 0.2% and 13.0%. Thus, mercury
      analyzers based on combustion can provide accurate estimates of organic carbon
      content in non-calcareous sediment and soils; however, weight gain from moisture
      (post-analysis), measurement uncertainty, and sample representativeness should
      all be taken into account. Sediment cores from seasonal wetland and open water
      areas from six oxbow lakes in the Mississippi River alluvial flood plain were
      analyzed. Wetland sediments generally had higher levels of Hg than open water
      areas owing to a greater fraction of fine particles and higher levels of organic
      matter. Annual loading of Hg in open water areas was estimated at 4.3, 13.4,
      19.2, 20.7, 129, and 135 ng cm(-2) yr(-1) for Beasley, Roundaway, Hampton,
      Washington, Wolf and Sky Lakes, respectively. Generally, the interval with the
      highest Hg flux was dated to the 1960s and 1970s.

PMID- 25847157
TI  - Large-scale identification of potential drug targets based on the topological
      features of human protein-protein interaction network.
AB  - Identifying potential drug target proteins is a crucial step in the process of
      drug discovery and plays a key role in the study of the molecular mechanisms of
      disease. Based on the fact that the majority of proteins exert their functions
      through interacting with each other, we propose a method to recognize target
      proteins by using the human protein-protein interaction network and graph theory.
      In the network, vertexes and edges are weighted by using the confidence scores of
      interactions and descriptors of protein primary structure, respectively. The
      novel network topological features are defined and employed to characterize
      protein using existing databases. A widely used minimum redundancy maximum
      relevance and random forests algorithm are utilized to select the optimal feature
      subset and construct model for the identification of potential drug target
      proteins at the proteome scale. The accuracies of training set and test set are
      89.55% and 85.23%. Using the constructed model, 2127 potential drug target
      proteins have been recognized and 156 drug target proteins have been validated in
      the database of drug target. In addition, some new drug target proteins can be
      considered as targets for treating diseases of mucopolysaccharidosis, non
      arteritic anterior ischemic optic neuropathy, Bernard-Soulier syndrome and pseudo
      von Willebrand, etc. It is anticipated that the proposed method may became a
      powerful high-throughput virtual screening tool of drug target. 

PMID- 25847158
TI  - Enzyme-free surface plasmon resonance aptasensor for amplified detection of
      adenosine via target-triggering strand displacement cycle and Au nanoparticles.
AB  - Herein, we combine the advantage of aptamer technique with the amplifying effect
      of an enzyme-free signal-amplification and Au nanoparticles (NPs) to design a
      sensitive surface plasmon resonance (SPR) aptasensor for detecting small
      molecules. This detection system consists of aptamer, detection probe (c-DNA1)
      partially hybridizing to the aptamer strand, Au NPs-linked hairpin DNA (Au-H
      DNA1), and thiolated hairpin DNA (H-DNA2) previously immobilized on SPR gold
      chip. In the absence of target, the H-DNA1 possessing hairpin structure cannot
      hybridize with H-DNA2 and thereby Au NPs will not be captured on the SPR gold
      chip surface. Upon addition of target, the detection probe c-DNA1 is forced to
      dissociate from the c-DNA1/aptamer duplex by the specific recognition of the
      target to its aptamer. The released c-DNA1 hybridizes with Au-H-DNA1 and opens
      the hairpin structure, which accelerate the hybridization between Au-H-DNA1 and H
      DNA2, leading to the displacement of the c-DNA1 through a branch migration
      process. The released c-DNA1 then hybridizes with another Au-H-DNA1 probe, and
      the cycle starts anew, resulting in the continuous immobilization of Au-H-DNA1
      probes on the SPR chip, generating a significant change of SPR signal due to the
      electronic coupling interaction between the localized surface plasma of the Au
      NPs and the surface plasma wave. With the use of adenosine as a proof-of
      principle analyte, this sensing platform can detect adenosine specifically with a
      detection limit as low as 0.21 pM, providing a simple, sensitive and selective
      protocol for small target molecules detection.

PMID- 25847159
TI  - Platinum nanoparticles functionalized nitrogen doped graphene platform for
      sensitive electrochemical glucose biosensing.
AB  - In this work, we reported an efficient platinum nanoparticles functionalized
      nitrogen doped graphene (PtNPs@NG) nanocomposite for devising novel
      electrochemical glucose biosensor for the first time. The fabricated PtNPs@NG and
      biosensor were characterized using transmission electron microscopy, high
      resolution transmission electron microscopy, X-ray photoelectron spectroscopy,
      static water contact angle, UV-vis spectroscopy, electrochemical impedance
      spectra and cyclic voltammetry, respectively. PtNPs@NG showed large surface area
      and excellent biocompatibility, and enhanced the direct electron transfer between
      enzyme molecules and electrode surface. The glucose oxidase (GOx) immobilized on
      PtNPs@NG nanocomposite retained its bioactivity, and exhibited a surface
      controlled, quasi-reversible and fast electron transfer process. The constructed
      glucose biosensor showed wide linear range from 0.005 to 1.1mM with high
      sensitivity of 20.31 mA M(-1) cm(-2). The detection limit was calculated to be
      0.002 mM at signal-to-noise of 3, which showed 20-fold decrease in comparison
      with single NG-based electrochemical biosensor for glucose. The proposed glucose
      biosensor also demonstrated excellent selectivity, good reproducibility,
      acceptable stability, and could be successfully applied in the detection of
      glucose in serum samples at the applied potential of -0.33 V. This research
      provided a promising biosensing platform for the development of excellent
      electrochemical biosensors.

PMID- 25847160
TI  - A dual-responsive fluorescence method for the detection of clenbuterol based on
      BSA-protected gold nanoclusters.
AB  - The illegal feeding of clenbuterol (CLB) to domestic animals and the potential
      harm of it to human health lead an urgent requirement for the efficient detection
      of CLB, especially in the edible meat. In this paper we reported a new
      fluorescence method for the detection of trace amount of CLB by using the BSA
      protected gold nanoclusters (AuNCs@BSA). Under the excitation of either 280 or
      500 nm the emission of AuNCs@BSA was quenched obviously by diazotized CLB,
      supplying a dual-responsive fluorescence method to detect CLB in aqueous
      solution. In addition, the linear response of the fluorescence intensity of
      AuNCs@BSA to diazotized CLB allowed the quantitative detection of CLB in a range
      of 4.0 nM-300 MUM upon excitation at two wavelength, and the limit of detection
      for CLB was 3.0 nM upon 280 nm excitation and 1.6 nM upon 500 nm excitation,
      respectively. In addition, the dual-responsive mechanism of AuNCs@BSA to CLB was
      investigated in detail by using several CLB analogues and reference compounds.
      Particularly, the proposed method was successfully applied to detect CLB in pork
      mince and the results were validated well by HPLC, illustrating it could be used
      as a reliable, rapid, and cost-effective technique for the determination of CLB
      residues in real samples.

PMID- 25847161
TI  - A highly selective molecularly imprinted electrochemiluminescence sensor for
      ultra-trace beryllium detection.
AB  - A new molecularly imprinted electrochemiluminescence (ECL) sensor was proposed
      for highly sensitive and selective determination of ultratrace Be(2+)
      determination. The complex of Be(2+) with 4-(2-pyridylazo)-resorcinol (PAR) was
      chosen as the template molecule for the molecularly imprinted polymer (MIP). In
      this assay, the complex molecule could be eluted from the MIP, and the cavities
      formed could then selectively recognize the complex molecules. The cavities
      formed could also work as the tunnel for the transfer of probe molecules to
      produce sound responsive signal. The determination was based on the intensity of
      the signal, which was proportional to the concentrations of the complex molecule
      in the sample solution, and the Be(2+) concentration could then be determined
      indirectly. The results showed that in the range of 7*10(-11 )mol L(-1) to
      8.0*10(-9) mol L(-1), the ECL intensity had a linear relationship with the Be(2+)
      concentrations, with the limit of detection of 2.35*10(-11) mol L(-1). This
      method was successfully used to detect Be(2+) in real water samples.

PMID- 25847162
TI  - Preparation and evaluation of poly(alkyl methacrylate-co-methacrylic acid-co
      ethylene dimethacrylate) monolithic columns for separating polar small molecules
      by capillary liquid chromatography.
AB  - In this study, methacrylic acid (MAA) was incorporated with alkyl methacrylates
      to increase the hydrophilicity of the synthesized ethylene dimethacrylate-based
      (EDMA-based) monoliths for separating polar small molecules by capillary LC
      analysis. Different alkyl methacrylate-MAA ratios were investigated to prepare a
      series of 30% alkyl methacrylate-MAA-EDMA monoliths in fused-silica capillaries
      (250-MUm i.d.). The porosity, permeability, and column efficiency of the
      synthesized MAA-incorporated monolithic columns were characterized. A mixture of
      phenol derivatives is employed to evaluate the applicability of using the
      prepared monolithic columns for separating small molecules. Fast separation of
      six phenol derivatives was achieved in 5 min with gradient elution using the
      selected poly(lauryl methacrylate-co-MAA-co-EDMA) monolithic column. In addition,
      the effect of acetonitrile content in mobile phase on retention factor and plate
      height as well as the plate height-flow velocity curves were also investigated to
      further examine the performance of the selected poly(lauryl methacrylate-co-MAA
      co-EDMA) monolithic column. Moreover, the applicability of prepared polymer-based
      monolithic column for potential food safety applications was also demonstrated by
      analyzing five aflatoxins and three phenicol antibiotics using the selected
      poly(lauryl methacrylate-co-MAA-co-EDMA) monolithic column.

PMID- 25847163
TI  - Trilinearity deviation ratio: a new metric for chemometric analysis of
      comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry
      data.
AB  - Comprehensive two-dimensional gas chromatography coupled with time-of-flight mass
      spectrometry (GC*GC-TOFMS) is a well-established instrumental platform for
      complex samples. However, chemometric data analysis is often required to fully
      extract useful information from the data. We demonstrate that retention time
      shifting from one modulation to the next, Delta(2)tR, is not sufficient alone to
      quantitatively describe the trilinearity of a single GC*GC-TOFMS run for the
      purpose of predicting the performance of the chemometric method parallel factor
      analysis (PARAFAC). We hypothesize that analyte peak width on second dimension
      separations, (2)Wb, also impacts trilinearity, along with Delta(2)tR. The term
      trilinearity deviation ratio, TDR, which is Delta(2)tR normalized by (2)Wb, is
      introduced as a quantitative metric to assess accuracy for PARAFAC of a GC*GC
      TOFMS data cube. We explore how modulation ratio, MR, modulation period, PM,
      temperature programming rate, Tramp, sampling phase (in-phase and out-of-phase),
      and signal-to-noise ratio, S/N, all play a role in PARAFAC performance in the
      context of TDR. Use of a PM in the 1-2 s range provides an optimized peak
      capacity for the first dimension separation (500-600) for a 30 min run, with an
      adequate peak capacity for the second dimension separation (12-15), concurrent
      with an optimized two-dimensional peak capacity (6000-7500), combined with
      sufficiently low TDR values (0-0.05) to facilitate low quantitative errors with
      PARAFAC (0-0.5%). In contrast, use of a PM in the 5s or greater range provides a
      higher peak capacity on the second dimension (30-35), concurrent with a lower
      peak capacity on the first dimension (100-150) for a 30 min run, and a slightly
      reduced two-dimensional peak capacity (3000-4500), and furthermore, the data are
      not sufficiently trilinear for the more retained second dimension peaks in order
      to directly use PARAFAC with confidence.

PMID- 25847164
TI  - Size and concentration determination of (functionalised) fullerenes in surface
      and sewage water matrices using field flow fractionation coupled to an online
      accurate mass spectrometer: method development and validation.
AB  - In order to assess the environmental risks of a compound it is imperative to have
      suitable and reliable techniques for its determination in environmental matrices.
      In this paper, we focused on a method development for the recently introduced
      online coupling of a field flow fractionation (FFF) system to an Orbitrap-HRMS,
      that allows the simultaneous size and concentration determination of different
      aqueous fullerene aggregates and their concentrations in different size
      fractions. A 0.05% NH4OH solution in water was identified as the best carrier
      liquid for the analysis of the three different aqueous fullerene suspensions (C60
      [60], [6,6]-phenyl-C61 butyric acid methyl ester ([60]PCBM) and [6,6]-(bis)phenyl
      C61 butyric acid methyl ester ([60]bisPCBM)). The multi-angle light scattering
      (MALS) data received after employing the ammonia solution was consistent with
      both the theory and calibration using well defined Au and latex particles. The
      LODs obtained using Orbitrap HRMS detection were 0.1 MUg L(-1) for an injection
      volume of 100 MUL which are significantly better than the LODs obtained by using
      UV (20 MUg L(-1)) and MALS detectors (5 MUg L(-1)). However, these LODs can be
      further improved as in theory there is no limit to the amount of sample that can
      be injected into the FFF. Environmental samples (river and sewage water) were
      spiked with fullerenes and the fractograms obtained for these samples revealed
      that the matrix does affect the size of fullerene aggregates. Information on the
      size distribution can be useful for the risk assessment of these particles.

PMID- 25847165
TI  - Fibre coupled micro-light emitting diode array light source with integrated band
      pass filter for fluorescence detection in miniaturised analytical systems.
AB  - In this work, a new type of miniaturized fibre-coupled solid-state light source
      is demonstrated as an excitation source for fluorescence detection in capillary
      electrophoresis. It is based on a parabolically shaped micro-light emitting diode
      (MU-LED) array with a custom band-pass optical interference filter (IF) deposited
      at the back of the LED substrate. The GaN MU-LED array consisted of 270
      individual MU-LED elements with a peak emission at 470 nm, each about 14 MUm in
      diameter and operated as a single unit. Light was extracted through the
      transparent substrate material, and coupled to an optical fibre (OF, 400 MUm in
      diameter, numerical aperture NA=0.37), to form an integrated MU-LED-IF-OF light
      source component. This packaged MU-LED-IF-OF light source emitted approximately
      225 MUW of optical power at a bias current of 20 mA. The bandpass IF filter was
      designed to reduce undesirable LED light emissions in the wavelength range above
      490 nm. Devices with and without IF were compared in terms of the optical power
      output, spectral characteristics as well as LOD values. While the IF consisted of
      only 7.5 pairs (15 layers) of SiO2/HfO2 layers, it resulted in an improvement of
      the baseline noise as well as the detection limit measured using fluorescein as
      test analyte, both by approximately one order of magnitude, with a LOD of 1*10(
      8) mol L(-1) obtained under optimised conditions. The MU-LED-IF-OF light source
      was then demonstrated for use in capillary electrophoresis with fluorimetric
      detection. The limits of detection obtained by this device were compared to those
      obtained with a commercial fibre coupled LED device.

PMID- 25847166
TI  - Severe acute abdomen caused by symptomatic Meckel's diverticulum in three
      children with trisomy 18.
AB  - Meckel's diverticulum (MD) is the most prevalent congenital anomaly of the
      gastrointestinal tract and often presents a diagnostic challenge. Patients with
      trisomy 18 frequently have MD, but the poor prognosis and lack of consensus
      regarding management for neonates has meant that precise information on the
      clinical manifestations in infants and children with MD is lacking. We describe
      the cases of three children with trisomy 18 who developed symptomatic MD.
      Intussusception was diagnosed in Patient 1, intestinal volvulus in Patient 2, and
      gastrointestinal bleeding in Patient 3. All three patients underwent surgical
      treatment and only the Patient 1 died due to pulmonary hypertensive crisis. The
      other two patients experienced no further episodes of abdominal symptoms. In
      patients with trisomy 18, although consideration of postoperative complications
      and prognosis after surgical treatment is necessary, symptomatic MD should carry
      a high index of suspicion in patients presenting with acute abdomen.

PMID- 25847168
TI  - Complex Adaptive Systems, soil degradation and land sensitivity to
      desertification: A multivariate assessment of Italian agro-forest landscape.
AB  - Degradation of soils and sensitivity of land to desertification are intensified
      in last decades in the Mediterranean region producing heterogeneous spatial
      patterns determined by the interplay of factors such as climate, land-use
      changes, and human pressure. The present study hypothesizes that rising levels of
      soil degradation and land sensitivity to desertification are reflected into
      increasingly complex (and non-linear) relationships between environmental and
      socioeconomic variables. To verify this hypothesis, the Complex Adaptive Systems
      (CAS) framework was used to explore the spatiotemporal dynamics of eleven
      indicators derived from a standard assessment of soil degradation and land
      sensitivity to desertification in Italy. Indicators were made available on a
      detailed spatial scale (773 agricultural districts) for various years (1960,
      1990, 2000 and 2010) and analyzed through a multi-dimensional exploratory data
      analysis. Our results indicate that the number of significant pair-wise
      correlations observed between indicators increased with the level of soil and
      land degradation, although with marked differences between northern and southern
      Italy. 'Fast' and 'slow' factors underlying soil and land degradation, and
      'rapidly-evolving' or 'locked' agricultural districts were identified according
      to the rapidity of change estimated for each of the indicators studied. In
      southern Italy, 'rapidly-evolving' districts show a high level of soil
      degradation and land sensitivity to desertification during the whole period of
      investigation. On the contrary, those districts in northern Italy are those
      experiencing a moderate soil degradation and land sensitivity to desertification
      with the highest increase in the level of sensitivity over time. The study
      framework contributes to the assessment of complex local systems' dynamics in
      affluent but divided countries. Results may inform thematic strategies for the
      mitigation of land and soil degradation in the framework of action plans to
      combat desertification. 

PMID- 25847167
TI  - Trihalomethane exposure and biomonitoring for the liver injury indicator, alanine
      aminotransferase, in the United States population (NHANES 1999-2006).
AB  - Exposure to trihalomethanes (or THMs: chloroform, bromoform,
      bromodichloromethane, and dibromochloromethane [DBCM]) formed via drinking water
      disinfection has been associated with adverse reproductive outcomes and cancers
      of the digestive or genitourinary organs. However, few studies have examined
      potential associations between THMs and liver injury in humans, even though
      experimental studies suggest that these agents exert hepatotoxic effects,
      particularly among obese individuals. This study examined participants in the
      National Health and Nutrition Examination Survey (1999-2006, N=2781) to test the
      hypothesis that THMs are associated with liver injury as assessed by alanine
      aminotransferase (ALT) activity in circulation. Effect modification by body mass
      index (BMI) or alcohol consumption also was examined. Associations between blood
      THM concentrations and ALT activity were assessed using unconditional multiple
      logistic regression to calculate prevalence odds ratios (ORs) with 95% confidence
      intervals (CIs) for exposure among cases with elevated ALT activity (men:
      >40IU/L, women: >30IU/L) relative to those with normal ALT, after adjustment for
      variables that may confound the relationship between ALT and THMs. Compared to
      controls, cases were 1.35 times more likely (95% CI: 1.02, 1.79) to have
      circulating DBCM concentrations exceeding median values in the study population.
      There was little evidence for effect modification by BMI, although the
      association varied by alcohol consumption. Among non-drinkers, cases were more
      likely than controls to be exposed to DBCM (OR: 3.30, 95% CI: 1.37, 7.90),
      bromoform (OR: 2.88, 95% CI: 1.21, 6.81), or brominated THMs (OR: 4.00, 95% CI:
      1.31, 12.1), but no association was observed among participants with low, or
      moderate to heavy alcohol consumption. Total THM levels exceeding benchmark
      exposure limits continue to be reported both in the United States and globally.
      Results from this study suggest a need for further characterization of ALT
      activity and possibly other hepatic or metabolic diseases in populations with
      elevated drinking water THM concentrations. 

PMID- 25847169
TI  - Selenium contaminated waters: An overview of analytical methods, treatment
      options and recent advances in sorption methods.
AB  - Selenium is an essential trace element for many organisms, including humans, but
      it is bioaccumulative and toxic at higher than homeostatic levels. Both selenium
      deficiency and toxicity are problems around the world. Mines, coal-fired power
      plants, oil refineries and agriculture are important examples of anthropogenic
      sources, generating contaminated waters and wastewaters. For reasons of human
      health and ecotoxicity, selenium concentration has to be controlled in drinking
      water and in wastewater, as it is a potential pollutant of water bodies. This
      review article provides firstly a general overview about selenium distribution,
      sources, chemistry, toxicity and environmental impact. Analytical techniques used
      for Se determination and speciation and water and wastewater treatment options
      are reviewed. In particular, published works on adsorption as a treatment method
      for Se removal from aqueous solutions are critically analyzed. Recent published
      literature has given particular attention to the development and search for
      effective adsorbents, including low-cost alternative materials. Published works
      mostly consist in exploratory findings and laboratory-scale experiments. Binary
      metal oxides and LDHs (layered double hydroxides) have presented excellent
      adsorption capacities for selenium species. Unconventional sorbents (algae,
      agricultural wastes and other biomaterials), in raw or modified forms, have also
      led to very interesting results with the advantage of their availability and low
      cost. Some directions to be considered in future works are also suggested. 

PMID- 25847170
TI  - Growth and (137)Cs uptake of four Brassica species influenced by inoculation with
      a plant growth-promoting rhizobacterium Bacillus pumilus in three contaminated
      farmlands in Fukushima prefecture, Japan.
AB  - The effectiveness of the plant growth-promoting rhizobacterium Bacillus pumilus
      regarding growth promotion and radiocesium ((137)Cs) uptake was evaluated in four
      Brassica species grown on different (137)Cs contaminated farmlands at Fukushima
      prefecture in Japan from June to August 2012. B. pumilus inoculation did not
      enhance growth in any of the plants, although it resulted in a significant
      increase of (137)Cs concentration and higher (137)Cs transfer from the soil to
      plants. The Brassica species exhibited different (137)Cs uptake abilities in the
      order Komatsuna>turnip>mustard>radish. TF values of (137)Cs ranged from 0.018 to
      0.069 for all vegetables. Komatsuna possessed the largest root surface area and
      root volume, and showed a higher (137)Cs concentration in plant tissue and higher
      (137)Cs TF values (0.060) than the other vegetables. Higher (137)Cs transfer to
      plants was prominent in soil with a high amount of organic matter and an Al
      vermiculite clay mineral type. 

PMID- 25847171
TI  - Remediating radium contaminated legacy sites: Advances made through machine
      learning in routine monitoring of "hot" particles.
AB  - The extensive use of radium during the 20th century for industrial, military and
      pharmaceutical purposes has led to a large number of contaminated legacy sites
      across Europe and North America. Sites that pose a high risk to the general
      public can present expensive and long-term remediation projects. Often the most
      pragmatic remediation approach is through routine monitoring operating gamma-ray
      detectors to identify, in real-time, the signal from the most hazardous
      heterogeneous contamination (hot particles); thus facilitating their removal and
      safe disposal. However, current detection systems do not fully utilise all
      spectral information resulting in low detection rates and ultimately an increased
      risk to the human health. The aim of this study was to establish an optimised
      detector-algorithm combination. To achieve this, field data was collected using
      two handheld detectors (sodium iodide and lanthanum bromide) and a number of
      Monte Carlo simulated hot particles were randomly injected into the field data.
      This allowed for the detection rate of conventional deterministic (gross counts)
      and machine learning (neural networks and support vector machines) algorithms to
      be assessed. The results demonstrated that a Neural Network operated on a sodium
      iodide detector provided the best detection capability. Compared to deterministic
      approaches, this optimised detection system could detect a hot particle on
      average 10cm deeper into the soil column or with half of the activity at the same
      depth. It was also found that noise presented by internal contamination
      restricted lanthanum bromide for this application. 

PMID- 25847172
TI  - Climate-driven terrestrial inputs in ultraoligotrophic mountain streams of Andean
      Patagonia revealed through chromophoric and fluorescent dissolved organic matter.
AB  - Fluvial networks transport a substantial fraction of the terrestrial production,
      contributing to the global carbon cycle and being shaped by hydrologic, natural
      and anthropogenic factors. In this investigation, four Andean Patagonian
      oligotrophic streams connecting a forested catchment (~125km(2)) and draining to
      a double-basin large and deep lake (Lake Moreno complex, Northwestern Patagonia),
      were surveyed to analyze the dynamics of the allochthonous subsidy. The results
      of a 30month survey showed that the catchment supplies nutrients and dissolved
      organic matter (DOM) to the streams. The eruption of the Puyehue-Cordon Caulle at
      the beginning of the study overlapped with seasonal precipitation events. The
      largest terrestrial input was timed with precipitation which increased
      particulate materials, nutrients and DOM through enhanced runoff. Baseline
      suspended solids and nutrients were very low in all the streams (suspended
      solids: ~1mg/L; total nitrogen: ~0.02mg/L; total phosphorus: ~5MUg/L), increasing
      several fold with runoff. Baseline dissolved organic carbon concentrations (DOC)
      ranged between 0.15 and 1mg/L peaking up to three-fold. Chromophoric and
      fluorescent analyses characterized the DOM as of large molecular weight and high
      aromaticity. Parallel factor modeling (PARAFAC) of DOM fluorescence matrices
      revealed three components of terrestrial origin, with certain degree of microbial
      processing: C1 and C2 (terrestrial humic-like compounds) and C3 (protein-like and
      pigment derived compounds). Seasonal changes in MOD quality represent different
      breakdown stages of the allochthonous DOM. Our survey allowed us to record and
      discuss the effects of the Puyehue-Cordon Caulle eruption, showing that due to
      the high slopes, high current and discharge of the streams the volcanic material
      was rapidly exported to the Moreno Lake complex. Overall, this survey underscores
      the magnitude and timing of the allochthonous input revealing the terrestrial
      subsidy to food webs in Patagonian freshwaters, which are among the most
      oligotrophic systems of the world. 

PMID- 25847173
TI  - Trihalomethane formation potential of aquatic and terrestrial fulvic and humic
      acids: Sorption on activated carbon.
AB  - Humic substances (HSs) are precursors for the formation of hazardous disinfection
      by-products (DBPs) during chlorination of water. Various surrogate parameters
      have been used to investigate the generation of DBPs by HS precursors and the
      removal of these precursors by activated carbon treatment. Dissolved organic
      carbon (DOC)- and ultraviolet absorbance (UVA254)-based isotherms are commonly
      reported and presumed to be good predictors of the trihalomethane formation
      potential (THMFP). However, THMFP-based isotherms are rarely published such that
      the three types of parameters have not been compared directly. Batch equilibrium
      experiments on activated carbon were used to generate constant-initial
      concentration sorption isotherms for well-characterized samples obtained from the
      International Humic Substances Society (IHSS). HSs representing type (fulvic acid
      [FA], humic acid [HA]), origin (aquatic, terrestrial), and geographical source
      (Nordic, Suwannee, Peat, Soil) were examined at pH6 and pH9. THMFP-based
      isotherms were generated and compared to determine if DOC- and UVA254-based
      isotherms were good predictors of the THMFP. The sorption process depended on the
      composition of the HSs and the chemical nature of the activated carbon, both of
      which were influenced by pH. Activated carbon removal of THM-precursors was pH-
      and HS-dependent. In some instances, the THMFP existed after UVA254 was depleted.

PMID- 25847174
TI  - Antifungal properties of silver nanoparticles against indoor mould growth.
AB  - The presence of moulds in indoor environments causes serious diseases and acute
      or chronic toxicological syndromes. In order to inhibit or prevent the growth of
      microorganisms on building materials, the disruption of their vital processes or
      the reduction of reproduction is required. The development of novel techniques
      that impair the growth of microorganisms on building materials is usually based
      on silver nanoparticles (AgNPs). It makes them an alternative to other biocides.
      AgNPs have proven antibacterial activity and became promising in relation to
      fungi. The aim of the study was to assess growth and morphology of mycelia of
      typical indoor fungal species: Penicillium brevicompactum, Aspergillus fumigatus,
      Cladosporium cladosporoides, Chaetomium globosum and Stachybotrys chartarum as
      well as Mortierella alpina, cultured on agar media. The antifungal activity of
      AgNPs was also tested in relation to C. globosum and S. chartarum grown on the
      surface of gypsum drywall. It was found that the presence of AgNPs in
      concentrations of 30-200mg/l significantly decreased the growth of fungi.
      However, in the case of M. alpina, AgNPs stimulated its growth. Moreover, strong
      changes in moulds morphology and colour were observed after administration of
      AgNPs. Parameters of conidiophores/sporangiophores varied depending on mould
      region and changed significantly after treatment with AgNPs. The experiments have
      shown antifungal properties of AgNPs against common indoor mould species. Their
      application to building materials could effectively protect indoor environments
      from mould development. However, consideration must be given to the fact that the
      growth of some fungal strains might be stimulated by AgNPs. 

PMID- 25847175
TI  - Quantification of potential exposure of gray partridge (Perdix perdix) to
      pesticide active substances in farmlands.
AB  - Estimating exposure of wild birds to plant protection products is of key
      importance in the risk assessment process evaluating their harmful potential. In
      this paper, we propose an ecologically-relevant methodology to estimate potential
      exposure to active substances (ASs) of a farmland focal bird, the gray partridge
      Perdix perdix. It is based on bird habitat use of fields at the time of pesticide
      applications. It accounts for spatio-temporal heterogeneity at population and
      landscape scales. We identify and quantify the potential exposure to 179 ASs of
      140 clutches during pre-laying, laying, and incubation phases, and of 75 coveys.
      The data come from a large scale field study combining radiotelemetry and a
      farmer survey. They were collected in 12 different representative sites. The
      proportion of clutches potentially exposed to a given chemical was >=5% for 32
      ASs; prothioconazole and epoxiconazole ranking first. 71% of clutches were
      potentially exposed to >=1 AS and 67% to >=2 ASs. Mixtures involved 2 to 22 ASs.
      They emerged from commercial formulations, tank mixtures, bird habitat use, and
      combinations. ASs were fungicides (53%), herbicides (25%), and insecticides (16%)
      used on a variety of crops in April-June, when ground-nesting birds are breeding.
      The European Food Safety Authority conclusions report a long-term first-tier
      toxicity-to-exposure ratio (TERlt) <5 for 11 out of 19 documented ASs, and higher
      tier TERlt <5 for 5 out of 10 ASs. This suggests a potential risk for bird
      reproduction in farmlands. Globally 13% of coveys were potentially exposed to 18
      ASs during the first month (1-4 coveys per AS). The use of our field data in
      future research and risk assessment is discussed. 

PMID- 25847176
TI  - The geochemical transformation of soils by agriculture and its dependence on soil
      erosion: An application of the geochemical mass balance approach.
AB  - Agricultural activities alter elemental budgets of soils and thus their long-term
      geochemical development and suitability for food production. This study examined
      the utility of a geochemical mass balance approach that has been frequently used
      for understanding geochemical aspect of soil formation, but has not previously
      been applied to agricultural settings. Protected forest served as a reference to
      quantify the cumulative fluxes of Ca, P, K, and Pb at a nearby tilled crop land.
      This comparison was made at two sites with contrasting erosional environments:
      relatively flat Coastal Plain in Delaware vs. hilly Piedmont in Pennsylvania.
      Mass balance calculations suggested that liming not only replenished the Ca lost
      prior to agricultural practice but also added substantial surplus at both sites.
      At the relatively slowly eroding Coastal Plain site, the agricultural soil
      exhibited enrichment of P and less depletion of K, while both elements were
      depleted in the forest soil. At the rapidly eroding Piedmont site, erosion
      inhibited P enrichment. In similar, agricultural Pb contamination appeared to
      have resulted in Pb enrichment in the relatively slowly eroding Coastal Plain
      agricultural soil, while not in the rapidly eroding Piedmont soils. We conclude
      that agricultural practices transform soils into a new geochemical state where
      current levels of Ca, P, and Pb exceed those provided by the local soil minerals,
      but such impacts are significantly offset by soil erosion. 

PMID- 25847177
TI  - Small intestinal lactoferrin and calprotectin levels in different stages of
      necrotizing enterocolitis in a rat model.
AB  - PURPOSE: Necrotizing enterocolitis (NEC) is a severe disease of mostly premature
      infants with high morbidity and mortality rates. There is no reliable biomarker
      for detecting newborns at risk for NEC development. We aimed to investigate small
      intestinal lactoferrin (LF) and calprotectin (CAL) levels as predictors and
      indicators of disease severity in an experimental newborn rat model. MATERIALS
      AND METHODS: Newborn pups were randomly divided into two groups, NEC and control.
      The NEC group pups were decapitated on the second, third and fourth days of the
      experiment for an assessment of the different stages of NEC. In the study group,
      hypoxia-reoxygenation model used to induce NEC. As biochemical parameters, small
      intestinal LF and CAL levels were measured with an enzyme-linked immunosorbent
      assay technique and intestinal injury scoring was evaluated as a pathologic
      parameter. RESULTS: Small intestinal levels of both LF and CAL increased in the
      second and the third day groups, but began to decrease by the fourth day. The
      first, second and third day levels of LF and CAL were higher than controls. The
      intestinal injury scores of all NEC groups were significantly higher than the
      control group. CONCLUSION: Small intestinal lactoferrin and calprotectin were
      good markers for demonstrating NEC. However, instead of spot testing, monitoring
      the levels of these markers may be more informative.

PMID- 25847178
TI  - D-dimer for risk stratification in haemodynamically stable patients with acute
      pulmonary embolism.
AB  - PURPOSE: Patients with submassive pulmonary embolism (PE) have a higher short
      term mortality than those with low-risk PE. Rapid identification of submassive PE
      is important for adequate treatment of non-massive PE. We aimed to investigate
      the utility of D-dimer for the prediction of submassive PE stadium in
      normotensive PE patients. PATIENTS AND METHODS: Normotensive PE patients were
      classified into submassive or low-risk PE groups. In addition to the comparison
      of the groups, area under the curve (AUC) and D-dimer cut-off for the prediction
      of submassive PE stadium, multi-variate logistic regression for association
      between D-dimer values above this cut-off and submassive PE stadium were also
      calculated. RESULTS: The data of 129 normotensive PE patients (59.7% women, mean
      age 70.0 years (60.7/81.0)) were analysed retrospectively. Patients with
      submassive PE were older (75.0 years (61.7/81.0) vs. 66.5 years (55.7/74.2),
      P=0.026) and more frequently female (63.6% vs. 53.8%, P=0.35). Heart rate
      (100.0beats/min (85.0/108.0) vs. 80.0beats/min (70.0/96.2), P<0.0001), systolic
      pulmonary-artery pressure (41.55+/-16.79mmHg vs. 22.62+/-14.81mmHg, P<0.0001),
      and D-dimer (2.00mg/l (1.09/3.98) vs. 1.21mg/l (0.75/1.99), P=0.011) were higher
      in patients with submassive PE. D-dimer values >1.32mg/l were indicative of
      submassive PE and shock-index >=0.7. The effectiveness (AUC) of the test was 0.63
      for submassive PE and 0.64 for shock-index >=0.7. D-dimer values >1.32mg/l were
      associated with submassive PE stadium (OR 3.81 (95% CI: 1.74-8.35), P=0.00083) as
      well as with systolic blood pressure (OR 0.98 (95% CI: 0.97-0.99), P=0.033),
      heart rate (OR 1.02 (95% CI: 1.00-1.04), P=0.023) and shock-index value (OR 15.89
      (95% CI: 1.94-130.08), P=0.0099). CONCLUSIONS: D-dimer values >1.32mg/l are
      indicative of submassive PE stadium and shock-index >=0.7. Efficacy of D-dimer
      for predicting submassive PE stadium was only weak to moderate.

PMID- 25847179
TI  - Dysfunctional prefrontal gamma-band oscillations reflect working memory and other
      cognitive deficits in schizophrenia.
AB  - Impairments in working memory (WM) and other cognitive functions are cardinal
      neuropsychological symptoms in schizophrenia (ScZ). The prefrontal cortex (PFC)
      is important for mediating and executing these functions. Functional neuroimaging
      and molecular studies have consistently shown PFC abnormalities in ScZ. In
      addition, recent studies have suggested that impairments in oscillatory activity,
      especially in the gamma band (approximately 30-80 Hz), reflect disturbed cortical
      information processing in this patient group. Here we review evidence that
      dysfunctional gamma-band responses (GBR) in the PFC could be a factor
      contributing to WM and other cognitive deficits in ScZ. We provide an overview of
      noninvasive electrophysiological studies reporting frontal GBR abnormalities in
      ScZ patients during WM and other cognitive tasks. In agreement with the often
      reported hypofrontality in functional neuroimaging studies, the majority of
      reviewed studies revealed reduced amplitudes or reduced phase locking of GBR over
      frontal areas in this patient group. Clinical implications derived from these
      findings and possibilities to foster future studies on GBR abnormalities in ScZ
      patients, are discussed. Since oscillatory activity in the gamma band has
      previously been linked to a variety of neurotransmitters, such as the gamma
      aminobutyric acid-ergic system, the study of prefrontal GBR could also have
      implications for pharmacologic approaches in the treatment of WM and other
      cognitive deficits in ScZ. 

PMID- 25847181
TI  - Parents' and children's acceptance of skim chocolate milks sweetened by monk
      fruit and stevia leaf extracts.
AB  - Chocolate milk increases milk consumption of children, but high sugar content
      raises health concerns. Interest in sugar reduction and parents' preference for
      natural sweeteners necessitates further research on natural nonnutritive
      sweeteners. However, it is important to maintain consumer acceptability,
      especially for children, while reducing sugar in chocolate milk. The objectives
      of this study were to identify the sweetness intensity perception of stevia leaf
      (STV) and monk fruit (MK) extracts in skim chocolate milk (SCM), to evaluate STV
      and MK as the sole or partial sweetener source for SCM for young adults (19 to 35
      y) and children (5 to 13 y), and to determine if information on natural
      nonnutritive sweeteners impacted parents' acceptability of SCM. Power function
      and 2-alternative forced choice studies were used to determine the iso-sweetness
      of nonnutritive sweeteners to a sucrose control in SCM (51.4 g/L, SUC control).
      Young adults (n = 131) evaluated 9 different SCM (SUC control, STV, MK,
      STV:sucrose blends, or MK:sucrose blends) in a completely randomized 2-d test.
      Children (n = 167) evaluated SUC control SCM and SCM with 39.7 g/L sucrose and 46
      mg/L MK (MK25) or 30 mg/L STV (STV25). Parents evaluated SUC control, MK25, and
      STV25 in a balanced crossover design with a 40-d wait time between primed or
      unprimed ballots. Chocolate milks solely sweetened by nonnutritive sweeteners
      were less acceptable compared with SUC control by young adults. MK25 and STV25
      were acceptable by young adults and children. The presentation of chocolate milk
      label information had different effects on parental acceptance. Traditional
      parents preferred sucrose sweetened SCM, and label conscious parents preferred
      SCM with natural nonnutritive sweeteners.

PMID- 25847182
TI  - Improving Milk Intake in Milk-Averse Lactose Digesters and Maldigesters.
AB  - OBJECTIVE: To determine whether a 21-day milk-drinking intervention could reverse
      milk aversion. DESIGN: Participants consumed increasing amounts of cow's milk for
      21 days. Milk and dairy consumption, aversion, and likeness were assessed pre-
      and post-intervention and at 3 and 6 months post-intervention. SETTING: A large
      Midwestern university. PARTICIPANTS: Twenty-seven milk-averse individuals
      completed the intervention, 26 completed the 3-month follow-up, and 24 completed
      the 6-month follow-up. MAIN OUTCOMES MEASURED: Participants self-reported milk
      and dairy consumption, aversion, and degree to which they liked milk. ANALYSIS:
      Analysis of variance determined between-subject effects. Independent samples t
      test determined the effect of time. Fisher exact test determined factors
      affecting milk consumption. RESULTS: Lactose digesters and maldigesters showed a
      significant decrease in overall symptom scores after the milk intervention, with
      no significant difference between groups. Independent of digestive status,
      subjects demonstrated a significant decrease in aversion, an increase in the
      amount to which they liked milk, and an increase in milk and overall calcium
      consumption at 3 and 6 months post-intervention. CONCLUSIONS AND IMPLICATIONS:
      The results suggest a reversal of milk avoidance and the possibility that milk
      avoiders can increase likeness and incorporate milk into their diet after
      exposure.

PMID- 25847180
TI  - In search of multimodal neuroimaging biomarkers of cognitive deficits in
      schizophrenia.
AB  - BACKGROUND: The cognitive deficits of schizophrenia are largely resistant to
      current treatments and thus are a lifelong illness burden. The Measurement and
      Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus
      Cognitive Battery (MCCB) provides a reliable and valid assessment of cognition
      across major cognitive domains; however, the multimodal brain alterations
      specifically associated with MCCB in schizophrenia have not been examined.
      METHODS: The interrelationships between MCCB and the abnormalities seen in three
      types of neuroimaging-derived maps-fractional amplitude of low-frequency
      fluctuations (fALFF) from resting-state functional magnetic resonance imaging
      (MRI), gray matter (GM) density from structural MRI, and fractional anisotropy
      from diffusion MRI-were investigated by using multiset canonical correlation
      analysis in data from 47 schizophrenia patients treated with antipsychotic
      medications and 50 age-matched healthy control subjects. RESULTS: One multimodal
      component (canonical variant 8) was identified as both group differentiating and
      significantly correlated with the MCCB composite. It demonstrated 1) increased
      cognitive performance associated with higher fALFF (intensity of regional
      spontaneous brain activity) and higher GM volumes in thalamus, striatum,
      hippocampus, and the mid-occipital region, with co-occurring fractional
      anisotropy changes in superior longitudinal fascicules, anterior thalamic
      radiation, and forceps major; 2) higher fALFF but lower GM volume in dorsolateral
      prefrontal cortex related to worse cognition in schizophrenia; and 3) distinct
      domains of MCCB might exhibit dissociable multimodal signatures, e.g., increased
      fALFF in inferior parietal lobule particularly correlated with decreased social
      cognition. Medication dose did not relate to these findings in schizophrenia.
      CONCLUSIONS: Our results suggest linked functional and structural deficits in
      distributed cortico-striato-thalamic circuits may be closely related to MCCB
      measured cognitive impairments in schizophrenia.

PMID- 25847184
TI  - Evaluation of Tc-99 m Labeled Dimeric GX1 Peptides for Imaging of Colorectal
      Cancer Vasculature.
AB  - PURPOSE: This study aimed to evaluate the potential of PEGylated dimeric GX1
      peptide as a radiotracer for imaging of colorectal cancer vasculature in a LoVo
      tumor xenografted mouse model. PROCEDURES: The [(99m)Tc]PEG-(GX1)2 peptide was
      synthesized and identified. Confocal immunofluorescence analysis, receptor
      binding assay, and competitive inhibition assay were performed to evaluate the
      binding specificity and the receptor binding affinity of PEG-(GX1)2 to Co-human
      umbilical vein endothelial cells (HUVECs). Single photon emission computed
      tomography imaging and biodistribution were performed to evaluate the targeting
      ability of PEG-(GX1)2 to colorectal cancer. RESULTS: The studies in vitro
      suggested that PEG-(GX1)2 co-localized with Factor VIII in the perinuclear
      cytoplasm of Co-HUVECs and bound specifically to Co-HUVECs with a high affinity.
      The studies in vivo demonstrated that the targeting efficacy of PEG-(GX1)2 was
      superior to GX1. CONCLUSIONS: PEGylation improved the affinity and the targeting
      ability of the GX1 peptide. PEG-(GX1)2 is a more promising probe for imaging of
      colorectal vasculature than GX1.

PMID- 25847185
TI  - Validation of a predictive model for the growth of chalk yeasts on bread.
AB  - The present study focused on the effects of temperature, T, and water activity,
      aw, on the growth of Hyphopichia burtonii, Pichia anomala, and Saccharomycopsis
      fibuligera on Sabouraud Agar Medium. Cardinal values were estimated by means of
      cardinal models with inflection. All the yeasts were xerophilic, and they
      exhibited growth at 0.85 aw. The combined effects of T, aw, and pH on the growth
      of these species were described by the gamma-concept and validated on bread in
      the range of 15-25  degrees C, 0.91-0.97 aw, and pH 4.6-6.8. The optimum growth
      rates on bread were 2.88, 0.259, and 1.06 mm/day for H. burtonii, P. anomala, and
      S. fibuligera, respectively. The optimal growth rate of S. fibuligera on bread
      was about 2 fold that obtained on Sabouraud. Due to reproduction by budding, P.
      anomala exhibited low growth on Sabouraud and bread. However, this species is of
      major concern in the baker's industry because of the production of ethyl acetate
      in bread.

PMID- 25847183
TI  - Development and validation of panoptic Meso scale discovery assay to quantify
      total systemic interleukin-6.
AB  - AIM: Interleukin-6 (IL-6), a multifunctional cytokine, exists in several forms
      ranging from a low molecular weight (MW 20-30 kDa) non-complexed form to high MW
      (200-450 kDa), complexes. Accurate baseline IL-6 assessment is pivotal to
      understand clinical responses to IL-6-targeted treatments. Existing assays
      measure only the low MW, non-complexed IL-6 form. The present work aimed to
      develop a validated assay to measure accurately total IL-6 (complexed and non
      complexed) in serum or plasma as matrix in a high throughput and easily
      standardized format for clinical testing. METHODS: Commercial capture and
      detection antibodies were screened against humanized IL-6 and evaluated in an
      enzyme-linked immunosorbent assay format. The best antibody combinations were
      screened to identify an antibody pair that gave minimum background and maximum
      recovery of IL-6 in the presence of 100% serum matrix. A plate-based total IL-6
      assay was developed and transferred to the Meso Scale Discovery (MSD) platform
      for large scale clinical testing. RESULTS: The top-performing antibody pair from
      36 capture and four detection candidates was validated on the MSD platform. The
      lower limit of quantification in human serum samples (n = 6) was 9.77 pg l(-1) ,
      recovery ranged from 93.13-113.27%, the overall pooled coefficients of variation
      were 20.12% (inter-assay) and 8.67% (intra-assay). High MW forms of IL-6, in size
      fractionated serum samples from myelodysplastic syndrome and rheumatoid arthritis
      patients, were detected by the assay but not by a commercial kit. CONCLUSION:
      This novel panoptic (sees all forms) IL-6 MSD assay that measures both high and
      low MW forms may have clinical utility.

PMID- 25847186
TI  - Stochastic modelling of Listeria monocytogenes single cell growth in cottage
      cheese with mesophilic lactic acid bacteria from aroma producing cultures.
AB  - A stochastic model was developed for simultaneous growth of low numbers of
      Listeria monocytogenes and populations of lactic acid bacteria from the aroma
      producing cultures applied in cottage cheese. During more than two years,
      different batches of cottage cheese with aroma culture were analysed for pH,
      lactic acid concentration and initial concentration of lactic acid bacteria.
      These data and bootstrap sampling were used to represent product variability in
      the stochastic model. Lag time data were estimated from observed growth data
      (lactic acid bacteria) and from literature on L. monocytogenes single cells.
      These lag time data were expressed as relative lag times and included in growth
      models. A stochastic model was developed from an existing deterministic growth
      model including the effect of five environmental factors and inter-bacterial
      interaction [Ostergaard, N.B, Eklow, A and Dalgaard, P. 2014. Modelling the
      effect of lactic acid bacteria from starter- and aroma culture on growth of
      Listeria monocytogenes in cottage cheese. International Journal of Food
      Microbiology. 188, 15-25]. Growth of L. monocytogenes single cells, using lag
      time distributions corresponding to three different stress levels, was simulated.
      The simulated growth was subsequently compared to growth of low concentrations
      (0.4-1.0 CFU/g) of L. monocytogenes in cottage cheese, exposed to similar
      stresses, and in general a good agreement was observed. In addition, growth
      simulations were performed using population relative lag time distributions for
      L. monocytogenes as reported in literature. Comparably good predictions were
      obtained as for the simulations performed using lag time data for individual
      cells of L. monocytogenes. Therefore, when lag time data for individual cells are
      not available, it was suggested that relative lag time distributions for L.
      monocytogenes can be used as a qualified default assumption when simulating
      growth of low concentrations of L. monocytogenes.

PMID- 25847187
TI  - Validity and reliability of the Chinese version of the Sheehan Disability Scale
      (SDS-C).
AB  - INTRODUCTIONS: This study aims to evaluate the validity and reliability of the
      Chinese version of the Sheehan Disability Scale (SDS-C) among depression patients
      in Taiwan. METHODS: To validate the SDS-C, two samples were selected: Sample 1 (n
      = 78) consisted of patients diagnosed with Depressive Disorder, while sample 2 (n
      = 63) consisted of a nondepressive population. Sample 1 was evaluated with SDS
      twice with 7-14 days interval to measure test-retest reliability. Both samples
      were also evaluated with The Centre for Epidemiologic Studies Depression Scale
      (CESD), Family APGAR (adaptation, partnership, growth, affection, resolve) score,
      the Global Assessment of Functioning (GAF), and brief questionnaire of the World
      Health Organization Quality of Life instrument (WHOQOL-BREF) and by a
      psychiatrist. The two samples were combined to measure validity. RESULTS: In
      concurrent validity, SDS-C scores were significantly correlated with the total
      score of GAF. The discriminative validity was carried out by comparing the score
      of SDS-C between subjects with and without current depressive disorder (t =
      12.32, df = 139, P < 0.001). Another discriminative validity by receiver
      operating characteristic analysis showed the optimal cut-point was >11
      (sensitivity: 82.1, specificity: 93.7). The area under the curve was 0.93 (+/
      0.02). For the factor validity, principal components analysis showed that a
      single factor solution was the best solution accounting for 88.9% of the
      variance. Regarding the construct validity, SDS-C scores were significantly
      correlated with CESD, WHOQOL-BREF, and the Family APGAR score. For test-retest
      reliability, the intra-class correlation coefficient for the total SDS-C score
      was 0.89 (95% confidence interval 0.82-0.93) and internal consistency Cronbach's
      alpha was 0.94. DISCUSSION: The SDS-C was found to be a valid and reliable
      instrument for current depressive disorder patients in Taiwan.

PMID- 25847188
TI  - Employment in Adults with Down Syndrome in the United States: Results from a
      National Survey.
AB  - BACKGROUND: There is no current data about employment/unemployment of adults with
      Down syndrome in the United States. The data that exists includes adults with
      Down syndrome as part of the larger group of people with disabilities or people
      with intellectual disability. METHOD: This study used a survey to investigate
      paid and volunteer employment, unemployment, types of jobs, job training, job
      settings, job schedules and job satisfaction in adults with Down syndrome. There
      were 511 survey responses received. RESULTS: Findings were that there is high
      unemployment for adults with Down syndrome and that current employment is in a
      limited number of fields, primarily in the areas of food, janitorial work,
      landscaping, and office work. A small percentage of respondents have full time
      paid employment. A combination of part time paid employment and unpaid volunteer
      work is typical. CONCLUSIONS: Implications for educators, counselors, legislators
      and employers are discussed.

PMID- 25847189
TI  - Predictors of 49-month mortality in Chinese nonagenarians and centenarians in
      PLAD study.
AB  - OBJECTIVE: To examine whether a set of well-known predictors of mortality in
      younger elderly also maintain their importance in Chinese oldest old group.
      DESIGN: A cross-sectional study of 1401 inhabitants aged 90 and older were
      conducted in the area of Dujiangyan, China. 825 subjects participated and were
      followed up for vital status after 49 months. Professional interviewers collected
      baseline data concerning socio-demographic characteristics, lifestyle habits,
      physical factors and geriatric assessment. Bivariate analysis was conducted
      between survivors and deceased. Cox regression models were used to evaluate
      predictors of mortality. RESULTS: Four hundred and thirty-six (52.8%) of 825
      participants eligible for the analysis died during the 49 months of follow-up
      period. Older age, comorbidity, lower MMSE score, lower ADL and IADL scores
      increased the risk of mortality in the study group. Multivariate analyses showed
      older age (HR = 1.03, 95% CI 1.01-1.07) and comorbidity (HR = 1.09, 95% CI 1.02
      1.17) were associated with mortality while female gender (HR = 0.61, 95% CI 0.43
      0.86), taking exercise (HR = 0.80, 95% CI 0.64-1.01) and higher MMSE scores (HR =
      0.96, 95% CI 0.94-0.99) showed a positive effect on survival. CONCLUSION: In
      Chinese nonagenarians and centenarians, age, gender, taking exercise, cognitive
      impairment and comorbidity at baseline show predictive power of oldest old
      mortality.

PMID- 25847192
TI  - The effect of chlorine and fluorine substitutions on tuning the ionization
      potential of benzoate-bridged paddlewheel diruthenium(ii, ii) complexes.
AB  - A series of paddlewheel diruthenium(ii, ii) complexes with various chlorine
      substituted benzoate ligands (Cl-series) was synthesized as tetrahydrofuran (THF)
      adducts [Ru2(ClxPhCO2)4(THF)2]; where ClxPhCO2(-) = o-chlorobenzoate, ; m
      chlorobenzoate, ; p-chlorobenzoate, ; 2,3-dichlorobenzoate, ; 2,4
      dichlorobenzoate, ; 2,5-dichlorobenzoate, ; 2,6-dichlorobenzoate, ; 3,4
      dichlorobenzoate, ; 3,5-dichlorobenzoate, ; 2,3,4-trichlorobenzoate, ; 2,3,5
      trichlorobenzoate, ; 2,4,5-trichlorobenzoate, ; 3,4,5-trichlorobenzoate, ;
      2,3,4,5-tetrachlorobenzoate, . This Cl-series and the previously synthesized F
      series together with four new fluorine-substituted derivatives,
      [Ru2(FxPhCO2)4(THF)2] (where FxPhCO2(-) = 2,3-difluorobenzoate, ; 2,4
      difluorobenzoate, ; 2,5-difluorobenzoate, ; 2,3,5-trifluorobenzoate, ), were
      experimentally characterized with respect to solid-state structure, magnetic
      properties and electrochemistry. By tuning the substituents of the benzoate
      ligands using chlorine or fluorine atoms, the redox potential (E1/2) for
      [Ru2(II,II)]/[Ru2(II,III)](+) varied over a wide range of potentials from -40 mV
      to 360 mV (vs. Ag/Ag(+) in THF). This was dependent on (i) the number of ortho
      substituents, i.e. non-, mono- and di-o-substituted groups, with quasi-Hammett
      parameters for ortho-Cl and -F substitutions (sigmao = -0.272 and -0.217,
      respectively) and (ii) the general Hammett constants, sigmam and sigmap, for each
      group. The HOMO energy level calculated on the basis of the atomic coordinates of
      the solid-state structure was strongly affected by Cl- and F-substitutions as
      well as the redox potential in solution, which emphasizes the steric contribution
      of ortho-substituents in the energy level giving a deviation of EHOMO < 0.3 eV
      and <0.55 eV for the Cl- and F-series, respectively. 

PMID- 25847190
TI  - Characterizing and Overriding the Structural Mechanism of the Quizartinib
      Resistant FLT3 "Gatekeeper" F691L Mutation with PLX3397.
AB  - Tyrosine kinase domain mutations are a common cause of acquired clinical
      resistance to tyrosine kinase inhibitors (TKI) used to treat cancer, including
      the FLT3 inhibitor quizartinib. Mutation of kinase "gatekeeper" residues, which
      control access to an allosteric pocket adjacent to the ATP-binding site, has been
      frequently implicated in TKI resistance. The molecular underpinnings of
      gatekeeper mutation-mediated resistance are incompletely understood. We report
      the first cocrystal structure of FLT3 with the TKI quizartinib, which
      demonstrates that quizartinib binding relies on essential edge-to-face aromatic
      interactions with the gatekeeper F691 residue, and F830 within the highly
      conserved Asp-Phe-Gly motif in the activation loop. This reliance makes
      quizartinib critically vulnerable to gatekeeper and activation loop substitutions
      while minimizing the impact of mutations elsewhere. Moreover, we identify
      PLX3397, a novel FLT3 inhibitor that retains activity against the F691L mutant
      due to a binding mode that depends less vitally on specific interactions with the
      gatekeeper position. SIGNIFICANCE: We report the first cocrystal structure of
      FLT3 with a kinase inhibitor, elucidating the structural mechanism of resistance
      due to the gatekeeper F691L mutation. PLX3397 is a novel FLT3 inhibitor with in
      vitro activity against this mutation but is vulnerable to kinase domain mutations
      in the FLT3 activation loop.

PMID- 25847191
TI  - Changes in Dpysl2 expression are associated with prenatally stressed rat
      offspring and susceptibility to schizophrenia in humans.
AB  - Exposure to stress during critical periods of fetal brain development is an
      environmental risk factor for the development of schizophrenia in adult
      offspring. In the present study, a repeated-variable stress paradigm was applied
      to pregnant rats during the last week of gestation, which is analogous to the
      second trimester of brain development in humans. Behavioral and proteomic
      analyses were conducted in prenatally-stressed (PNS) adult offspring and non
      stressed (NS) adult controls. In the behavioral tests, grooming behavior in the
      social interaction test, line-crossing behavior in the open field test, and
      swimming behavior in the forced swimming test were decreased in the PNS group.
      Western blot analysis and immunohistochemical analysis revealed that the
      expression of dihydropyrimidinase-like 2 (Dpysl2) or collapsin response mediator
      protein 2 (Crmp2) was downregulated in the prefrontal cortex and hippocampus of
      rats in the PNS group. Subsequently, single-nucleotide polymorphisms (SNPs) of
      the human dihydropyrimidinase-like 2 (DPYSL2) gene were analyzed in a population.
      Two functional SNPs (rs9886448 in the promoter region and rs2289593 in the exon
      region) were associated with susceptibility to schizophrenia. The present
      findings demonstrated that the downregulation of genes such as Dpysl2 and Dypsl3
      in a rat model of prenatal stress may affect subsequent behavioral changes and
      that polymorphisms of the DPYSL2 gene in humans may be associated with the
      development of schizophrenia. Taken together with previous studies investigating
      the association between the DPYSL2 gene and schizophrenia, the present findings
      may contribute additional evidence regarding developmental theories of the
      pathophysiology of schizophrenia.

PMID- 25847193
TI  - Rice cyclophilin OsCYP18-2 is translocated to the nucleus by an interaction with
      SKIP and enhances drought tolerance in rice and Arabidopsis.
AB  - Cyclophilin 18-2 (CYP18-2) genes, homologues of human peptidyl-prolyl isomerase
      like 1 (PPiL1), are conserved across multicellular organisms and
      Schizosaccharomyces pombe. Although PPiL1 is known to interact with ski
      interacting protein (SKIP), a transcriptional co-regulator and spliceosomal
      component, there have been no functional analyses of PPiL1 homologues in plants.
      Rice cyclophilin 18-2 (OsCYP18-2) bound directly to amino acids 56-95 of OsSKIP
      and its binding was independent of cyclosporin A, a cyclophilin-binding drug.
      Moreover, OsCYP18-2 exhibited PPIase activity regardless of its interaction with
      OsSKIP. Therefore, the binding site for OsCYP18-2's interaction with SKIP was
      distinct from the PPIase active site. OsCYP18-2's interaction with SKIP full
      length protein enabled OsCYP18-2's translocation from the cytoplasm into the
      nucleus and AtSKIP interacted in planta with both AtCYP18-2 and OsCYP18-2.
      Drought and salt stress induced similar expression of OsCYP18-2 and OsSKIP.
      Overexpression of OsCYP18-2 in transgenic rice and Arabidopsis thaliana plants
      enhanced drought tolerance and altered expression and pre-mRNA splicing patterns
      of stress-related genes in Arabidopsis under drought conditions. Furthermore,
      OsCYP18-2 caused transcriptional activation with/without OsSKIP in the GAL4
      system of yeast; thus the OsSKIP-OsCYP18-2 interaction has an important role in
      the transcriptional and post-transcriptional regulation of stress-related genes
      and increases tolerance to drought stress. 

PMID- 25847194
TI  - Recurrence after stapled haemorrhoidopexy.

PMID- 25847195
TI  - "Wrap technique": a new operative procedure using a self-adhesive prosthesis for
      laparoscopic ventral rectopexy.
AB  - The aim of the present study was to describe and assess a new method of fixation
      using a self-adhesive prosthesis (Adhesix(TM)) in laparoscopic ventral rectopexy
      (LVR). The technical principles are based on a very low dissection and the
      adhesive properties of the prosthesis which can be applied to the rectum without
      stitches or staples. The prosthesis is made from polypropylene coated with a
      synthetic hydrogel. The binding of the prosthesis to rectum and vagina takes
      place in a wet environment after a few minutes and enables the shaping of the
      mesh on the surface of the rectum (wrap effect). Between March 2010 and March
      2013, 41 patients were operated on using LVR with a self-adhesive prosthesis. The
      effectiveness of prosthesis fixation was evaluated in a subset of 27 patients
      suffering from complete rectal prolapse. With a median follow-up of 30 months,
      there were no major complications and no recurrence. In this initial experience,
      LVR with a self-adhesive prosthesis does not increase the risk of recurrence. No
      undesirable effects were associated with the prosthesis.

PMID- 25847196
TI  - Thrombin generation measured as thrombin-antithrombin complexes predicts clinical
      outcomes in patients with cirrhosis.
AB  - AIM: Hypercoagulability has been detected in patients with cirrhosis yet its
      clinical significance remains unclear. We investigated the association of
      hypercoagulability with clinical outcomes in patients with cirrhosis. METHODS:
      Thrombin-antithrombin (TAT) complexes as thrombin generation (TG) marker, D
      dimer, antithrombin (AT), protein C, protein S, international normalized ratio
      (INR), activated partial thromboplastin time, fibrinogen, Child-Pugh class and
      Model for End-Stage Liver Disease (MELD) were evaluated. Two different
      multivariate analyses were performed: one not including MELD (model 1) and one
      including MELD and excluding INR (model 2). RESULTS: Eighty-one patients (Child
      Pugh class A/B/C: 27/27/27) and 40 healthy subjects were enrolled. Only
      TauAlphaTau and AT were independently associated with increasing liver disease
      severity. Increased TAT levels and MELD score were significantly associated with
      ascites and varices at baseline. Independent predictors of follow-up events were:
      TAT and MELD score for new-onset ascites; TAT and AT for variceal bleeding (VB);
      TAT and AT for portal vein thrombosis (PVT); and TAT and MELD for mortality. TAT
      equaled MELD in mortality prediction at 12 and 18 months. TAT cut-offs at 5.35,
      14.6, 13.5 and 9.25 ng/mL identified patient groups with significantly higher
      probability of new-onset ascites, VB, PVT and mortality, respectively.
      CONCLUSION: Increased TG is strongly correlated with portal hypertension-related
      complications, PVT and mortality in patients with cirrhosis. Measuring TG by TAT
      could enable risk stratification and institution of preventive strategies to
      improve clinical outcomes.

PMID- 25847197
TI  - Concordance of bacterial communities of two tick species and blood of their
      shared rodent host.
AB  - High-throughput sequencing is revealing that most macro-organisms house diverse
      microbial communities. Of particular interest are disease vectors whose
      microbiome could potentially affect pathogen transmission and vector competence.
      We investigated bacterial community composition and diversity of the ticks
      Dermacentor variabilis (n = 68) and Ixodes scapularis (n = 15) and blood of their
      shared rodent host, Peromyscus leucopus (n = 45) to quantify bacterial diversity
      and concordance. The 16S rRNA gene was amplified from genomic DNA from field
      collected tick and rodent blood samples, and 454 pyrosequencing was used to
      elucidate their bacterial communities. After quality control, over 300 000
      sequences were obtained and classified into 118 operational taxonomic units
      (OTUs, clustered at 97% similarity). Analysis of rarefied communities revealed
      that the most abundant OTUs were tick species-specific endosymbionts, Francisella
      and Rickettsia, and the commonly flea-associated bacterium Bartonella in rodent
      blood. An Arsenophonus and additional Francisella endosymbiont were also present
      in D. variabilis samples. Rickettsia was found in both tick species but not in
      rodent blood, suggesting that it is not transmitted during feeding. Bartonella
      was present in larvae and nymphs of both tick species, even those scored as
      unengorged. Relatively, few OTUs (e.g. Bartonella, Lactobacillus) were found in
      all sample types. Overall, bacterial communities from each sample type were
      significantly different and highly structured, independent of their dominant
      OTUs. Our results point to complex microbial assemblages inhabiting ticks and
      host blood including infectious agents, tick-specific endosymbionts and
      environmental bacteria that could potentially affect arthropod-vectored disease
      dynamics.

PMID- 25847198
TI  - An acoustic feature-based similarity scoring system for speech rehabilitation
      assistance.
AB  - The purpose of this study is to develop a tool to assist speech therapy and
      rehabilitation, which focused on automatic scoring based on the comparison of the
      patient's speech with another normal speech on several aspects including pitch,
      vowel, voiced-unvoiced segments, strident fricative and sound intensity. The
      pitch estimation employed the use of cepstrum-based algorithm for its robustness;
      the vowel classification used multilayer perceptron (MLP) to classify vowel from
      pitch and formants; and the strident fricative detection was based on the major
      peak spectral intensity, location and the pitch existence in the segment. In
      order to evaluate the performance of the system, this study analyzed eight
      patient's speech recordings (four males, four females; 4-58-years-old), which had
      been recorded in previous study in cooperation with Taipei Veterans General
      Hospital and Taoyuan General Hospital. The experiment result on pitch algorithm
      showed that the cepstrum method had 5.3% of gross pitch error from a total of
      2086 frames. On the vowel classification algorithm, MLP method provided 93%
      accuracy (men), 87% (women) and 84% (children). In total, the overall results
      showed that 156 tool's grading results (81%) were consistent compared to 192
      audio and visual observations done by four experienced respondents. Implication
      for Rehabilitation Difficulties in communication may limit the ability of a
      person to transfer and exchange information. The fact that speech is one of the
      primary means of communication has encouraged the needs of speech diagnosis and
      rehabilitation. The advances of technology in computer-assisted speech therapy
      (CAST) improve the quality, time efficiency of the diagnosis and treatment of the
      disorders. The present study attempted to develop tool to assist speech therapy
      and rehabilitation, which provided simple interface to let the assessment be done
      even by the patient himself without the need of particular knowledge of speech
      processing while at the same time, also provided further deep analysis of the
      speech, which can be useful for the speech therapist.

PMID- 25847199
TI  - [Aspirin hypersensitivity: characteristics and diagnostic approach].
AB  - INTRODUCTION: In routine medical practice, the diagnosis of aspirin
      hypersensitivity (AH) remains difficult. No clinical feature or biomarker is
      available to reliably confirm this diagnosis and oral provocation tests (OPT) are
      rarely performed. AIM: To compare asthmatics with and without AH. METHOD: The
      clinical characteristics of 21 asthmatics with and 24 without AH respectively
      were determined. AH was defined by a positive OPT. A full blood count was done
      before and 24 hours after the OPT. RESULTS: The medical history was associated
      with a weak sensitivity (52%) and a good specificity (96%) for assessing the
      diagnosis of AH. There was a higher prevalence of AH in women, and a higher
      frequency of allergic rhinitis in AH, but no characteristic was useful to
      facilitate the diagnosis of AH in asthmatic patients. Our results demonstrate
      higher values of platelets in AH patients. Following OPT, in AH patients only, a
      decrease in blood eosinophils and an increase in neutrophils was observed.
      CONCLUSIONS: These results confirm that the diagnosis of AH is challenging, with
      the history having only weak sensitivity. The observation that fluctuations in
      eosinophils and neutrophils occur following OPT in AH patients only warrants
      further investigations and suggests a rapid pro-inflammatory role for aspirin.

PMID- 25847200
TI  - [Is the asthmatic patient competent to manage his disease? A study of 280
      patients in Seine-Saint-Denis, France].
AB  - INTRODUCTION: The correct use of medication and the ability to assess the
      severity of the disease and to react appropriately in the case of exacerbation
      are essential objectives in the management of asthma patients. This study,
      conducted in a school of asthma in Seine-Saint-Denis, aims to measure the
      influence of socio-demographic and clinical factors, before any educational
      process, on these four security skills. METHODS: A prospective observational
      study concerning 280 consecutive patients managed between 2008 and 2011 (70 %
      women, mean age: 44 years [14-85 years]; deprivation: 48 %; born abroad: 39 %,
      low level of education: 23 %). The initial educational diagnosis was compared
      with the clinical and socio-demographic characteristics. RESULTS: In relation to
      asthma control, social characteristics (unemployment, deprivation), geographic or
      ethnic origin and educational level significantly influence the command of all or
      some of the security skills. In medical terms, a period of evolution of the
      disease of less than 10 years, outpatient follow-up without specialized
      monitoring and the absence of recent exacerbations also appear as predictors of
      inappropriate conduct in the management of the disease. CONCLUSIONS: This study
      suggests new priority targets for therapeutic education in asthma.

PMID- 25847201
TI  - [AIRBAg study: preliminary results after one year of screening for COPD in dairy
      farmers].
AB  - INTRODUCTION: The AIRBAg study screens for bronchial obstruction in dairy
      farmers. We present the preliminary results after one year. METHODS: A
      prospective screening study based on questionnaires and electronic mini
      spirometry (Neo-6((r))) that includes a representative sample of dairy farmers
      from the departments of Morbihan and Ile-et-Vilaine in Brittany. The dairy
      farmers had an occupational medicine appointment and, if they demonstrated at
      least one marker of possible bronchial obstruction (chronic cough, chronic
      bronchitis, dyspnoea, wheezing, FEV1/FEV6<0.8), they were referred to a
      pulmonologist. The data we present here were extracted from the occupational
      medicine appointments because the pulmonologists' appointments are still running.
      RESULTS: Among the 277 dairy farmers included, 125 (45%) demonstrated "possible
      bronchial obstruction". The total score of the CAT questionnaire was higher in
      these farmers (9.1+/-6.2 versus 5.8+/-4.0; P<0.0001). In multivariate analysis
      markers of "possible bronchial obstruction" were eczema, manual foddering and
      duration of mechanical straw litter spreading. CONCLUSION: Occupational medicine
      appointments identified markers of "possible bronchial obstruction". We will have
      the complete results from AIRBAg study in 2015.

PMID- 25847202
TI  - [Acceptability and compliance to long-term continuous positive pressure
      treatment].
AB  - INTRODUCTION: Compliance with continuous positive pressure treatment (CPAP) is a
      determining factor in the management of the obstructive sleep apnea syndrome
      (OSAS). Long-term compliance has been poorly studied. METHODS: The probability of
      long-term continuation of CPAP was evaluated retrospectively by an analysis of
      survival in 252 patients treated by CPAP after a screening of 472 patients during
      the years 2002 and 2003. RESULTS: Twenty-eight patients fulfilling the criteria
      for CPAP immediately refused the treatment. The mean follow-up for the 252
      treated patients was 76.9+/-46.4 months, with 38 patients having died and 75
      having discontinued treatment during the period. The 136 patients who continued
      treatment used CPAP for a mean of 7.4+/-1.6hours daily. The probability of
      continuing treatment was 71% at 5 years and 68% at 10 years. The severity of OSAS
      was a predictive factor for long-term CPAP compliance, with a 10-year compliance
      of 82% in patients having an apnoea/hypopnoea index >60, versus 68% with an index
      between 30-60 and 44% with an index <30. CONCLUSION: Long-term CPAP treatment is
      globally well accepted, with a 68% probability of continuing treatment for 10
      years, particularly in the most severely affected patients. Long-term daily
      compliance is very satisfactory.

PMID- 25847203
TI  - [Chemotherapy at the end of life for patients with lung cancer. A practice
      analysis].
AB  - RATIONALE: Few studies have analyzed the aggressiveness of the care (continuation
      of active treatments) at the end of life in patients with lung cancer. The
      objective of this study was to assess practices in this setting in a university
      department of respiratory medicine. PATIENTS AND METHODS: This retrospective
      study has consecutively included all patients who were managed for lung cancer
      and died over a period of 18 months. The analysis focused on the characteristics
      of the patients, the modalities of cancer treatment and the delays between the
      last active treatment and death. RESULTS: The overall median survival of the 94
      patients included was 9.6 months; 92% of patients having received at least one
      active treatment. During the 4 and 2 weeks periods preceding death, respectively
      55% and 22% of the patients received active treatments. The median time between
      the last day of active treatment and death was 27 days. CONCLUSION: These
      results, in concordance with the published data, showed that end of life active
      treatment in patients with lung cancer is a complex problem. We need prospective
      multicentric studies, with testing tools allowing better sharing of the decisions
      on active treatment between the medical team, the patient and his family.

PMID- 25847204
TI  - [Prevalence of tobacco smoking in primary and secondary schools in the Department
      of Dakar, Senegal].
AB  - INTRODUCTION: Tobacco smoke is a global health problem, and the largest avoidable
      cause of death in the world. The objective of our study was to determine the
      prevalence of tobacco smoking in schools in Dakar area (Senegal). MATERIEL AND
      METHODS: This descriptive and analytical cross-sectional study was performed from
      September 2011 to June 2012 in 27 schools of the Dakar area. RESULTS: We
      questioned 1654 students over a 9-month school period. The mean age was 15+/
      2.5years (range 11-22). The sample included 848 boys (51.3 %), therefore a sex
      ratio of 1.05. There were 68 smokers (4.1 %) and 60 ex-smokers (3.6 %). The mean
      age of the smokers was 16.9+/-2.2years (range 11-22) with a male preponderance of
      70.6 % (n=48). Smoking in family members was the initiating factor most
      frequently reported by smokers (25 %). The average age of ex-smokers was 16.4+/
      2years. Fear of parents' reactions was the most frequently invoked reason for
      stopping smoking (41.7 %). CONCLUSION: This study confirms the reality of smoking
      among school children in Senegal and highlights the urgency of the installation
      of a prevention policy near the young people.

PMID- 25847205
TI  - [Mesothelioma and familial Mediterranean fever: A relationship?].
AB  - INTRODUCTION: The majority of pleural and peritoneal mesotheliomas are linked to
      asbestos exposure but, in around 20% of cases, no history of such exposure is
      found. Periodic disease is associated with recurrent serositis, which could favor
      the development of mesothelioma. CASE REPORT: We report a case of pleural
      mesothelioma in a 50-year-old Lebanese woman, with no detectable exposure to
      asbestos but suffering from periodic disease (familial Mediterranean fever) with
      recurrent episodes of serositis. DISCUSSION: Many cases of peritoneal
      mesothelioma in patients with FMF are reported in the literature. This is the
      second reported case of pleural mesothelioma associated with periodic disease.
      Because of the low incidence of both diseases, further publications are required
      to support the hypothesis of a causal link. It is important, therefore, that all
      cases of an association of periodic disease and mesothelioma are reported.

PMID- 25847206
TI  - [Chronic Farmer's lung disease with emphysema].
AB  - INTRODUCTION: Farmer's lung (FL) is the most common type of hypersensitivity
      pneumonitis (HP), with an estimated prevalence of between 0.5 and 1.5% in dairy
      farmers. In chronic FL, fibrotic sequelae are widely described in the literature
      although our experience and occasional epidemiological studies emphasize an
      increased risk of developing emphysema in these patients. CASE REPORT: We report
      a case of FL in a 37-year-old patient with typical clinical features (exertional
      dyspnoea, lymphocytic alveolitis and computed tomography appearances) together
      with proven allergen exposure. This patient developed early pulmonary emphysema
      probably due to intermittent massive exposure to antigens and to bacterial and
      fungal micro-organisms. CONCLUSION: The current classification of HP
      differentiates acute, subacute and chronic forms but does not take account of the
      role of the mode of exposure and the evolution of the disease. The prognosis and
      evolution of HP seem to be dependent on the type and pattern of exposure. A new
      classification with two clusters has been suggested: in type 1, massive and
      intermittent exposure, as in FL, may lead to emphysema with chronic airflow
      obstruction and, in type 2, chronic exposure to a low level, as in bird fanciers,
      may lead to fibrosis with a restrictive pattern.

PMID- 25847207
TI  - [Noninvasive ventilation: efficacy of a new ventilatory mode in patients with
      obesity-hypoventilation syndrome].
AB  - Noninvasive ventilation is recommended to correct the nocturnal hypoventilation
      and relieve the symptoms of patients with the obesity-hypoventilation syndrome
      (OHS). The benefits of fixed pressure ventilation (S/T technology) are recognized
      but limited on account of the variability of nocturnal ventilatory requirements.
      The new technique AVAPS-AE (automatic EPAP) allows adjustment of the pressure
      according to the volume currently targeted. Its efficacy has not yet been
      evaluated. Our objectives are to evaluate firstly, whether AVAPS-AE optimizes the
      benefits of S/T technology on sleep architecture and quality, secondly, whether
      these benefits are associated with an improvement in gas exchange, symptoms,
      exercise tolerance, level of physical activity and quality of life of patients
      with OHS. In this multicenter trial, 60 newly diagnosed patients with OHS will be
      randomized to the control (S/T) and trial (AVAPS-AE) groups. A standardized
      titration procedure will be followed for the calibration of the ventilators.
      Functional evaluations (polysomnography, blood gases, impedance measurements and
      walking tests), questionnaires (physical activity, quality of life, quality of
      sleep and daytime somnolence) visual scales (fatigue, headaches) and a recording
      of activity will be undertaken after two months of ventilation. 

PMID- 25847208
TI  - [Multiple lung nodules and mediastinal widening of unusual etiology].

PMID- 25847209
TI  - [Diffuse and circumferential expiratory collapse].

PMID- 25847210
TI  - [Echocardiography and pulmonary hypertension: experience of the competence centre
      in Tours, France].

PMID- 25847211
TI  - Lipoxin A4 inhibits proliferation and inflammatory cytokine/chemokine production
      of human epidermal keratinocytes associated with the ERK1/2 and NF-kappaB
      pathways.
AB  - BACKGROUND: Current in vitro studies show that lipoxin A4 (LXA4) has multiple
      biological functions including inhibiting cell proliferation and inflammatory
      cytokine production. Our previous studies showed LXA4 could inhibit the
      expression of IL-6 and IL-8 in normal human epidermal keratinocytes (NHEKs).
      However, more specific effects including regulation of cell proliferation and
      anti-inflammatory mechanisms of LXA4 in NHEKs have not been previously studied.
      OBJECTIVE: We proposed to investigate the effects of LXA4 on cell proliferation
      and inflammatory cytokine/chemokine production in NHEKs, and the possible
      molecular mechanisms of cell cycle and anti-inflammatory signal transduction
      pathway. METHODS: NHEKs were stimulated with LPS, with or without preincubation
      with LXA4. Cell proliferation and cell cycle of NHEKs were examined by WST-8,
      CFSE assay and DNA staining, respectively. The mRNA and protein levels of
      inflammatory cytokines were quantified by real-time quantitative PCR and ELISA.
      The expressions of signaling proteins cyclin D1, P16INK4A, ERK1/2 and NF-kappaB
      p65 were analyzed using Western blotting. RESULTS: Cell proliferation and
      inflammatory cytokine/chemokine production of NHEKs were suppressed by LXA4,
      which caused G0/G1 phase cell cycle arrest in NHEKs. The expression of cyclin D1
      was down-regulated by LXA4, contrary to the results of P16INK4A. The ERK1/2
      phosphorylation and NF-kappaB-p65 nuclear translocation of NHEKs were both
      suppressed by LXA4. CONCLUSION: Cell growth and inflammatory cytokine/chemokine
      production of NHEKs were inhibited by LXA4, and the inhibitory effects might be
      associated with the mechanisms of cyclin D1/P16INK4A, ERK1/2 and NF-kappaB signal
      transduction pathway.

PMID- 25847212
TI  - Multi-location wheat stripe rust QTL analysis: genetic background and epistatic
      interactions.
AB  - KEY MESSAGE: Epistasis and genetic background were important influences on
      expression of stripe rust resistance in two wheat RIL populations, one with
      resistance conditioned by two major genes and the other conditioned by several
      minor QTL. Stripe rust is a foliar disease of wheat (Triticum aestivum L.) caused
      by the air-borne fungus Puccinia striiformis f. sp. tritici and is present in
      most regions around the world where commercial wheat is grown. Breeding for
      durable resistance to stripe rust continues to be a priority, but also is a
      challenge due to the complexity of interactions among resistance genes and to the
      wide diversity and continuous evolution of the pathogen races. The goal of this
      study was to detect chromosomal regions for resistance to stripe rust in two
      winter wheat populations, 'Tubbs'/'NSA-98-0995' (T/N) and 'Einstein'/'Tubbs'
      (E/T), evaluated across seven environments and mapped with diversity array
      technology and simple sequence repeat markers covering polymorphic regions of
      ~1480 and 1117 cM, respectively. Analysis of variance for phenotypic data
      revealed significant (P < 0.01) genotypic differentiation for stripe rust among
      the recombinant inbred lines. Results for quantitative trait loci/locus (QTL)
      analysis in the E/T population indicated that two major QTL located in
      chromosomes 2AS and 6AL, with epistatic interaction between them, were
      responsible for the main phenotypic response. For the T/N population, eight QTL
      were identified, with those in chromosomes 2AL and 2BL accounting for the largest
      percentage of the phenotypic variance.

PMID- 25847213
TI  - Cardiac Response During Auditory Selective Attention to Tones and Affective
      Sounds.
AB  - We conducted an experiment to determine if attention to affective sounds showed a
      lateral bias. Twenty-two participants were instructed to respond to one of two
      pure tones presented monaurally and to a set of pleasant and unpleasant sounds
      from the International Affective Digitized Sounds set. Participants were
      instructed to respond to pleasant or unpleasant sounds in the right or left ear,
      attending to pleasant/right, pleasant/left, unpleasant/right, and unpleasant/left
      sounds in separate blocks. Evoked cardiac response to the tones showed
      significant cardiac deceleration in response to attended sounds in the attended
      ear. In addition, pleasant sounds elicited significant cardiac deceleration when
      attended in the right ear, but not in the left. Unpleasant sounds elicited
      significant cardiac deceleration when attended in both ears. Consistent with the
      anterior valence hypothesis, our data suggests that pleasant sounds are mainly
      processed in the left hemisphere, but in contrast to this hypothesis, unpleasant
      sounds are processed bilaterally. 

PMID- 25847214
TI  - Social Cultivation of Vaccine Refusal and Delay among Waldorf (Steiner) School
      Parents.
AB  - U.S. media reports suggest that vastly disproportionate numbers of un- and under
      vaccinated children attend Waldorf (private alternative) schools. After
      confirming this statistically, I analyzed qualitative and quantitative
      vaccination-related data provided by parents from a well-established U.S. Waldorf
      school. In Europe, Waldorf-related non-vaccination is associated with
      anthroposophy (a worldview foundational to Waldorf education)-but that was not
      the case here. Nor was simple ignorance to blame: Parents were highly educated
      and dedicated to self-education regarding child health. They saw vaccination as
      variously unnecessary, toxic, developmentally inappropriate, and profit driven.
      Some vaccine caution likely predated matriculation, but notable post-enrollment
      refusal increases provided evidence of the socially cultivated nature of vaccine
      refusal in the Waldorf school setting. Vaccine caution was nourished and
      intensified by an institutionalized emphasis on alternative information and by
      school community norms lauding vaccine refusal and masking uptake. Implications
      for intervention are explored.

PMID- 25847215
TI  - Are antidepressants mood destabilizers?

PMID- 25847216
TI  - Wine protein haze: mechanisms of formation and advances in prevention.
AB  - Protein haze is an aesthetic problem in white wines that can be prevented by
      removing the grape proteins that have survived the winemaking process. The haze
      forming proteins are grape pathogenesis-related proteins that are highly stable
      during winemaking, but some of them precipitate over time and with elevated
      temperatures. Protein removal is currently achieved by bentonite addition, an
      inefficient process that can lead to higher costs and quality losses in
      winemaking. The development of more efficient processes for protein removal and
      haze prevention requires understanding the mechanisms such as the main drivers of
      protein instability and the impacts of various wine matrix components on haze
      formation. This review covers recent developments in wine protein instability and
      removal and proposes a revised mechanism of protein haze formation. 

PMID- 25847217
TI  - Understanding expressions of public grief: 'mourning sickness', 'grief-lite', or
      something more?

PMID- 25847218
TI  - Higher risk for adverse obstetric outcomes among immigrants of African and Asian
      descent: a comparison study at a low-risk maternity hospital in Norway.
AB  - BACKGROUND: Immigrants have higher risks for some adverse obstetric outcomes, and
      40 percent of women giving birth at the low-risk maternity ward in Baerum
      Hospital, Norway, are immigrants. This study compared obstetric outcomes between
      immigrants and ethnic Norwegians giving birth in a low-risk setting. METHODS:
      This was a population-based study linking the Medical Birth Registry of Norway to
      Statistics Norway. The study included the first registered birth during the study
      period to immigrant and ethnic Norwegian women at Baerum Hospital from 2006 to
      2010. The main outcome measures were onset of labor, operative vaginal delivery,
      cesarean delivery, episiotomy, postpartum bleeding > 500 mL, epidural analgesia,
      labor dystocia, gestational age, meconium-stained liquor, 5-minute Apgar score,
      birthweight, and transfer to a neonatal intensive care unit. RESULTS: A total of
      11,540 women originating from 141 countries were divided into seven groups.
      Compared with Norwegians, women from East, Southeast, and Central Asia had
      increased risk for operative vaginal delivery, postpartum bleeding, and low Apgar
      score. The African women had increased risk for postterm birth, meconium-stained
      liquor, episiotomy, operative vaginal delivery, emergency cesarean delivery,
      postpartum bleeding, low Apgar score, and low birthweight. Women from South and
      Western Asia had increased risk for low birthweight. CONCLUSION: Obstetric
      outcomes of immigrants differ significantly from those of Norwegians, even in a
      low-risk maternity unit. Thus, immigrant women would benefit from more targeted
      care during pregnancy and childbirth, even in low-risk settings.

PMID- 25847219
TI  - The low oxygen, oxidative and osmotic stress responses synergistically act
      through the ethylene response factor VII genes RAP2.12, RAP2.2 and RAP2.3.
AB  - The ethylene response factor VII (ERF-VII) transcription factor RELATED TO
      APETALA2.12 (RAP2.12) was previously identified as an activator of the ALCOHOL
      DEHYDROGENASE1 promoter::luciferase (ADH1-LUC) reporter gene. Here we show that
      overexpression of RAP2.12 and its homologues RAP2.2 and RAP2.3 sustains ABA
      mediated activation of ADH1 and activates hypoxia marker genes under both anoxic
      and normoxic conditions. Inducible expression of all three RAP2s conferred
      tolerance to anoxia, oxidative and osmotic stresses, and enhanced the sensitivity
      to abscisic acid (ABA). Consistently, the rap2.12-2 rap2.3-1 double mutant showed
      hypersensitivity to both submergence and osmotic stress. These findings suggest
      that the three ERF-VII-type transcription factors play roles in tolerance to
      multiple stresses that sequentially occur during and after submergence in
      Arabidopsis. Oxygen-dependent degradation of RAP2.12 was previously shown to be
      mediated by the N-end rule pathway. During submergence the RAP2.12, RAP2.2 and
      RAP2.3 are stabilized and accumulates in the nucleus affecting the transcription
      of stress response genes. We conclude that the stabilized RAP2 transcription
      factors can prolong the ABA-mediated activation of a subset of osmotic responsive
      genes (e.g. ADH1). We also show that RAP2.12 protein level is affected by the
      REALLY INTERESTING GENE (RING) domain containing SEVEN IN ABSENTIA of Arabidopsis
      thaliana 2 (SINAT2). Silencing of SINAT1/2 genes leads to enhanced RAP2.12
      abundance independently of the presence or absence of its N-terminal degron.
      Taken together, our results suggest that RAP2.12 and its homologues RAP2.2 and
      RAP2.3 act redundantly in multiple stress responses. Alternative protein
      degradation pathways may provide inputs to the RAP2 transcription factors for the
      distinct stresses.

PMID- 25847220
TI  - Mutation of CHRNA2 in a family with benign familial infantile seizures: Potential
      role of nicotinic acetylcholine receptor in various phenotypes of epilepsy.
AB  - Nicotinic acetylcholine receptor genes are involved mainly in nocturnal frontal
      epilepsy. Despite extensive studies, to date, the alpha2 subunit did not show a
      strong association with this peculiar epileptic phenotype. We report CHRNA2
      missense mutation in a family with benign familial infantile seizures (BFIS).
      TrueSeq Custom Amplicon (TSCA) sequencing approach was used to screen 10 ion
      channel genes in patients with idiopathic epilepsies. TSCA revealed a
      heterozygous single-nucleotide substitution in CHRNA2 gene (c.1126 C>T; p.
      Arg376Trp) that segregated in a family with BFIS; based on bio-informatics
      inspection, the change was predicted to be pathogenic. The investigated family
      includes parents and their three daughters. In affected individuals, seizures
      started between 6 and 24 months of age. Seizures were mainly in cluster and well
      controlled. Outcome was good in all subjects. Even if nicotinic acetylcholine
      receptor genes are traditionally associated with autosomal dominant nocturnal
      frontal lobe epilepsy (ADNFLE), this single-family description can open new
      possibilities in the genetic diagnosis, molecular characterization, and
      management of CHRNA2-related epilepsy. The pathogenic conversion of arginine 376
      to tryptophan alters all of these interactions in the cytoplasmic domain, never
      reported to be involved in epileptogenic mechanism. Further functional tests will
      be necessary to strongly relate CHRNA2 mutation with BFIS phenotype.

PMID- 25847222
TI  - "(Diphosphine)Nickel"-catalyzed negishi cross-coupling: an experimental and
      theoretical study.
AB  - The use of a strongly donating "(bis-dialkylphosphine)Ni" fragment promotes the
      catalytic coupling of a large range of ArCl and ArZnCl derivatives under mild
      conditions. Stoichiometric mechanistic investigations and DFT calculations prove
      that a Ni(0) /Ni(II) cycle is operative in this system. 

PMID- 25847221
TI  - Myasthenia gravis: descriptive analysis of life-threatening events in a recent
      nationwide registry.
AB  - BACKGROUND AND PURPOSE: Myasthenia gravis (MG) may become life-threatening if
      patients have respiratory insufficiency or dysphagia. This study aimed to
      determine the incidence, demographic characteristics, risk factors, response to
      treatment and outcome of these life-threatening events (LTEs) in a recent,
      population-based sample of MG patients. METHODS: A retrospective analysis of MG
      patients who presented with an LTE between 2000 and 2013 was performed.
      Participants were identified from a neuromuscular diseases registry in Spain that
      includes 648 patients with MG (NMD-ES). RESULTS: Sixty-two (9.56%) patients had
      an LTE. Thirty-two were classified as class V according to the MG Foundation of
      America, and 30 as class IVB. Fifty per cent were previously diagnosed with MG
      and median duration of the disease before the LTE was 24 months (3-406). The most
      common related factor was infection (n = 18). All patients received intravenous
      human immunoglobulin; 11 had a second infusion and six had plasma exchange.
      Median time to feeding tube removal was 13 days (1-434). Median time to weaning
      from ventilation was 12 days (3-176), and it was significantly shorter in late
      onset MG (>=50 years) (P = 0.019). LTEs improved <2 weeks in 55.8% but did not
      improve until after 1 month in 20% of patients. Four patients died. No other
      factors influenced mortality or duration of LTEs. CONCLUSIONS: The percentage of
      LTEs in MG patients was low, particularly amongst those previously diagnosed and
      treated for the disease. The significant percentage of treatment-resistant LTEs
      indicates that more effective treatment approaches are needed for this vulnerable
      sub-population.

PMID- 25847223
TI  - IL-6 blockade reverses the abnormal STAT activation of peripheral blood
      leukocytes from rheumatoid arthritis patients.
AB  - Considering the interplay of multiple STATs in response to cytokines, we
      investigated how IL-6 and its blocking affect STAT signaling in rheumatoid
      arthritis (RA). Leukocytes obtained from RA patients before and after tocilizumab
      treatment and healthy donors (HDs) were cytokine-stimulated and STAT
      phosphorylation was analyzed by cytometry. RA patients had significantly fewer
      pSTAT1+, pSTAT3+, and pSTAT6+ monocytes and pSTAT5+ lymphocytes than HDs. After
      24weeks of treatment, percentages of IFNgamma-induced pSTAT1+ and IL-10-induced
      pSTAT3+ monocytes in RA patients increased, reaching levels comparable to HDs.
      pSTAT1+ and pSTAT3+ cells correlated inversely with RA disease activity index and
      levels of pSTAT+ cells at baseline were higher in patients with good EULAR
      response to tocilizumab. IFNgamma-induced pSTAT1+ cells correlated inversely with
      memory T cells and anti-CCP levels. IL-10-induced pSTAT3+ cells correlated with
      Treg/Teff ratio. Our findings suggest that IL-6 blocking reduces the inflammatory
      mechanisms through the correction of STAT1 and STAT3 activation status. 

PMID- 25847224
TI  - Projected future distribution of date palm and its potential use in alleviating
      micronutrient deficiency.
AB  - BACKGROUND: Micronutrient deficiency develops when nutrient intake does not match
      nutritional requirements for maintaining healthy tissue and organ functions which
      may have long-ranging effects on health, learning ability and productivity.
      Inadequacy of iron, zinc and vitamin A are the most important micronutrient
      deficiencies. Consumption of a 100 g portion of date flesh from date palm
      (Phoenix dactylifera L.) has been reported to meet approximately half the daily
      dietary recommended intake of these micronutrients. This study investigated the
      potential distribution of P. dactylifera under future climates to address its
      potential long-term use as a food commodity to tackle micronutrient deficiencies
      in some developing countries. RESULTS: Modelling outputs indicated large shifts
      in areas conducive to date palm cultivation, based on global-scale alteration
      over the next 60 years. Most of the regions suffering from micronutrient
      deficiencies were projected to become highly conducive for date palm cultivation.
      CONCLUSIONS: These results could inform strategic planning by government and
      agricultural organizations by identifying areas to cultivate this nutritionally
      important crop in the future to support the alleviation of micronutrient
      deficiencies.

PMID- 25847226
TI  - Iatrogenic injury to the sciatic nerve during surgical repair of proximal
      hamstring avulsion.

PMID- 25847225
TI  - Prehospital and Emergency Care: Updates from the Disease Control Priorities,
      Version 3.
AB  - BACKGROUND: It is increasingly understood that emergency care systems can be cost
      effective in low- and middle-income countries (LMICs). The development of such
      systems, however, is still a work in progress. This article updates previous work
      in providing the most recent estimates of the burden of disease sensitive to
      emergency care, the current state of knowledge on the feasibility of emergency
      care, effect on outcomes, and cost-effectiveness in LMICs, and future directions
      for research, policy, and implementation. METHODS: We calculated the potential
      impact of prehospital and emergency care systems using updated and revised data
      based on the global burden of disease study. We then assessed the state of
      current knowledge and potential future directions for research and policy by
      conducting a review of the literature on current systems in LMICs. RESULTS:
      According to these newest updates, 24 million deaths related to emergency medical
      conditions occur in LMICs annually, accounting for an estimated 932 million years
      of life lost. Evidence shows that multiple emergency care models can function in
      different local settings, depending on resources and urbanicity. Emergency care
      can significantly improve mortality rates from emergent conditions and be highly
      cost-effective. Further research is needed on implementation of emergency care
      systems as they become a necessary reality in developing nations worldwide.
      CONCLUSIONS: Emergency care implementation in LMICs presents both challenges and
      opportunities. Investment in evidence-based emergency care, research on
      implementation, and system coordination in LMICs could lead to a more cost- and
      outcome-effective emergency care system than exists in advanced economies.

PMID- 25847227
TI  - Open-label prospective study of the safety and efficacy of glass-based yttrium 90
      radioembolization for infiltrative hepatocellular carcinoma with portal vein
      thrombosis.
AB  - BACKGROUND: The safety and efficacy of yttrium 90 ((90) Y) therapy for
      unresectable infiltrative hepatocellular carcinoma (HCC) with portal vein
      thrombosis (PVT) requires further evaluation. METHODS: A prospective, single
      center safety and feasibility study recruited patients with unresectable
      (Barcelona Clinic Liver Cancer stage C) infiltrative HCC with PVT. Safety was
      assessed according to Common Terminology Criteria for Adverse Events version 4.0.
      Overall survival (OS) and time to progression (TTP) were measured from the first
      (90) Y therapy. Survival analysis was performed with Kaplan-Meier estimation.
      Prognostic factors were tested with a log-rank test and Cox proportional
      regression analysis. RESULTS: Overall, 45 patients were recruited, and 30
      patients who met the study's inclusion criteria underwent glass-based (90) Y
      therapy. Four patients (13%) had transient hepatobiliary toxicity (grade >= 2).
      Ten patients (33%) had related emergency department visits, with 5 patients (17%)
      requiring short-term hospitalization. No radiation pneumonitis, gastrointestinal
      ulceration, or procedure-related mortality occurred. The median OS was 13 months
      (95% confidence interval, 4.4-22 months) with a TTP of 9 months (95% confidence
      interval, 6.2-13.1 months). Absence of ascites, an international normalized ratio
      < 1.2, an Eastern Cooperative Oncology Group (ECOG) performance status of 0,
      Child-Pugh class A, a macroaggregated albumin lung shunt fraction (LSF) < 10%,
      and no hepatobiliary toxicity were significant predictors of prolonged OS
      according to a univariate analysis (P < .05). A multivariate analysis found an
      ECOG performance status of 0, Child-Pugh class A, an LSF < 10%, and lack of
      transient hepatobiliary toxicity (grade >= 2) to be independent predictors of
      prolonged OS (P < .05). An ECOG performance status of 0, Child-Pugh class A, and
      an LSF < 10% were also predictors of prolonged TTP according to the multivariate
      analysis (P < .05). CONCLUSIONS: In patients with unresectable infiltrative HCC
      and PVT, (90) Y therapy appears to be a safe and viable therapy.

PMID- 25847228
TI  - Dependence Assessment in Human Reliability Analysis Using Evidence Theory and
      AHP.
AB  - Dependence assessment among human errors in human reliability analysis (HRA) is
      an important issue. Many of the dependence assessment methods in HRA rely heavily
      on the expert's opinion, thus are subjective and may sometimes cause
      inconsistency. In this article, we propose a computational model based on the
      Dempster-Shafer evidence theory (DSET) and the analytic hierarchy process (AHP)
      method to handle dependence in HRA. First, dependence influencing factors among
      human tasks are identified and the weights of the factors are determined by
      experts using the AHP method. Second, judgment on each factor is given by the
      analyst referring to anchors and linguistic labels. Third, the judgments are
      represented as basic belief assignments (BBAs) and are integrated into a fused
      BBA by weighted average combination in DSET. Finally, the CHEP is calculated
      based on the fused BBA. The proposed model can deal with ambiguity and the degree
      of confidence in the judgments, and is able to reduce the subjectivity and
      improve the consistency in the evaluation process. 

PMID- 25847229
TI  - 4q21 microdeletion in a patient with epilepsy and brain malformations.

PMID- 25847230
TI  - Melamine foam in Dentistry.

PMID- 25847231
TI  - Expression of stress-related proteins in Sediminibacterium sp. growing under
      planktonic conditions.
AB  - Aggregation is a common trait of bacteria in natural and engineered biological
      systems. Microbial aggregates, such as flocs, granules, and biofilms, are
      spatially heterogeneous environments. It is generally observed that by growing
      under aggregated conditions bacteria respond and adapt to environmental stress
      better than free-swimming bacteria of the same species. We performed a proteomic
      analysis of a strain of Sediminibacterium, isolated from activated sludge, which
      grew planktonically in diluted culture media and in an aggregated form in media
      containing a high concentration of organic substrate. Auto-aggregation was also
      observed in the presence of pyruvate in dilute media. Expression of a number of
      stress-related proteins significantly increased under planktonic growth in
      comparison to aggregate growth. The upregulated proteins, identified by MALDI-TOF
      mass spectrometry, were two isoforms of a protein belonging to the universal
      stress family (UspA), a thioredoxin-disulfide reductase, the Campylobacter jejuni
      orthologue transcriptional regulator (Cj1172c), and the CocE/NonD hydrolase. We
      conclude that Sediminibaterium sp. C3 growth is stressed under planktonic
      conditions and that aggregation induced by pyruvate protects the bacteria against
      oxidative stress. 

PMID- 25847232
TI  - CyclinA2-Cyclin-dependent Kinase Regulates SAMHD1 Protein Phosphohydrolase
      Domain.
AB  - SAMHD1 is a nuclear deoxyribonucleoside triphosphate triphosphohydrolase that
      contributes to the control of cellular deoxyribonucleoside triphosphate (dNTP)
      pool sizes through dNTP hydrolysis and modulates the innate immune response to
      viruses. CyclinA2-CDK1/2 phosphorylates SAMHD1 at Thr-592, but how this
      modification controls SAMHD1 functions in proliferating cells is not known. Here,
      we show that SAMHD1 levels remain relatively unchanged during the cell division
      cycle in primary human T lymphocytes and in monocytic cell lines. Inactivation of
      the bipartite cyclinA2-CDK-binding site in the SAMHD1 C terminus described herein
      abolished SAMHD1 phosphorylation on Thr-592 during S and G2 phases thus
      interfering with DNA replication and progression of cells through S phase. The
      effects exerted by Thr-592 phosphorylation-defective SAMHD1 mutants were
      associated with activation of DNA damage checkpoint and depletion of dNTP
      concentrations to levels lower than those seen upon expression of wild type
      SAMHD1 protein. These disruptive effects were relieved by either mutation of the
      catalytic residues of the SAMHD1 phosphohydrolase domain or by a Thr-592
      phosphomimetic mutation, thus linking the Thr-592 phosphorylation state to the
      control of SAMHD1 dNTPase activity. Our findings support a model in which
      phosphorylation of Thr-592 by cyclinA2-CDK down-modulates, but does not
      inactivate, SAMHD1 dNTPase in S phase, thereby fine-tuning SAMHD1 control of dNTP
      levels during DNA replication. 

PMID- 25847233
TI  - Hetero-oligomeric Complex between the G Protein-coupled Estrogen Receptor 1 and
      the Plasma Membrane Ca2+-ATPase 4b.
AB  - The new G protein-coupled estrogen receptor 1 (GPER/GPR30) plays important roles
      in many organ systems. The plasma membrane Ca(2+)-ATPase (PMCA) is essential for
      removal of cytoplasmic Ca(2+) and for shaping the time courses of Ca(2+)
      dependent activities. Here, we show that PMCA and GPER/GPR30 physically interact
      and functionally influence each other. In primary endothelial cells, GPER/GPR30
      agonist G-1 decreases PMCA-mediated Ca(2+) extrusion by promoting PMCA tyrosine
      phosphorylation. GPER/GPR30 overexpression decreases PMCA activity, and G-1
      further potentiates this effect. GPER/GPR30 knockdown increases PMCA activity,
      whereas PMCA knockdown substantially reduces GPER/GPR30-mediated phosphorylation
      of the extracellular signal-related kinase (ERK1/2). GPER/GPR30 co
      immunoprecipitates with PMCA with or without treatment with 17beta-estradiol,
      thapsigargin, or G-1. Heterologously expressed GPER/GPR30 in HEK 293 cells co
      localizes with PMCA4b, the main endothelial PMCA isoform. Endothelial cells
      robustly express the PDZ post-synaptic density protein (PSD)-95, whose knockdown
      reduces the association between GPER/GPR30 and PMCA. Additionally, the
      association between PMCA4b and GPER/GPR30 is substantially reduced by truncation
      of either or both of their C-terminal PDZ-binding motifs. Functionally,
      inhibition of PMCA activity is significantly reduced by truncation of
      GPER/GPR30's C-terminal PDZ-binding motif. These data strongly indicate that
      GPER/GPR30 and PMCA4b form a hetero-oligomeric complex in part via the anchoring
      action of PSD-95, in which they constitutively affect each other's function.
      Activation of GPER/GPR30 further inhibits PMCA activity through tyrosine
      phosphorylation of the pump. These interactions represent cross-talk between
      Ca(2+) signaling and GPER/GPR30-mediated activities. 

PMID- 25847234
TI  - Localization and Function of Pals1-associated Tight Junction Protein in
      Drosophila Is Regulated by Two Distinct Apical Complexes.
AB  - The transmembrane protein Crumbs (Crb) and its intracellular adaptor protein
      Pals1 (Stardust, Sdt in Drosophila) play a crucial role in the establishment and
      maintenance of apical-basal polarity in epithelial cells in various organisms. In
      contrast, the multiple PDZ domain-containing protein Pals1-associated tight
      junction protein (PATJ), which has been described to form a complex with Crb/Sdt,
      is not essential for apical basal polarity or for the stability of the Crb/Sdt
      complex in the Drosophila epidermis. Here we show that, in the embryonic
      epidermis, Sdt is essential for the correct subcellular localization of PATJ in
      differentiated epithelial cells but not during cellularization. Consistently, the
      L27 domain of PATJ is crucial for the correct localization and function of the
      protein. Our data further indicate that the four PDZ domains of PATJ function, to
      a large extent, in redundancy, regulating the function of the protein.
      Interestingly, the PATJ-Sdt heterodimer is not only recruited to the apical cell
      cell contacts by binding to Crb but depends on functional Bazooka (Baz). However,
      biochemical experiments show that PATJ associates with both complexes, the Baz
      Sdt and the Crb-Sdt complex, in the mature epithelium of the embryonic epidermis,
      suggesting a role of these two complexes for the function of PATJ during the
      development of Drosophila. 

PMID- 25847235
TI  - Fatty Acid-binding Proteins 1 and 2 Differentially Modulate the Activation of
      Peroxisome Proliferator-activated Receptor alpha in a Ligand-selective Manner.
AB  - Nuclear hormone receptors (NHRs) regulate the expression of proteins that control
      aspects of reproduction, development and metabolism, and are major therapeutic
      targets. However, NHRs are ubiquitous and participate in multiple physiological
      processes. Drugs that act at NHRs are therefore commonly restricted by toxicity,
      often at nontarget organs. For endogenous NHR ligands, intracellular lipid
      binding proteins, including the fatty acid-binding proteins (FABPs), can
      chaperone ligands to the nucleus and promote NHR activation. Drugs also bind
      FABPs, raising the possibility that FABPs similarly regulate drug activity at the
      NHRs. Here, we investigate the ability of FABP1 and FABP2 (intracellular lipid
      binding proteins that are highly expressed in tissues involved in lipid
      metabolism, including the liver and intestine) to influence drug-mediated
      activation of the lipid regulator peroxisome proliferator-activated receptor
      (PPAR) alpha. We show by quantitative fluorescence imaging and gene reporter
      assays that drug binding to FABP1 and FABP2 promotes nuclear localization and
      PPARalpha activation in a drug- and FABP-dependent manner. We further show that
      nuclear accumulation of FABP1 and FABP2 is dependent on the presence of
      PPARalpha. Nuclear accumulation of FABP on drug binding is driven largely by
      reduced nuclear egress rather than an increased rate of nuclear entry. Importin
      binding assays indicate that nuclear access occurs via an importin-independent
      mechanism. Together, the data suggest that specific drug-FABP complexes can
      interact with PPARalpha to effect nuclear accumulation of FABP and NHR
      activation. Because FABPs are expressed in a regionally selective manner, this
      may provide a means to tailor the patterns of NHR drug activation in a tissue
      specific manner. 

PMID- 25847236
TI  - Cytokinetic Failure-induced Tetraploidy Develops into Aneuploidy, Triggering Skin
      Aging in Phosphovimentin-deficient Mice.
AB  - Tetraploidy, a state in which cells have doubled chromosomal sets, is observed in
      ~20% of solid tumors and is considered to frequently precede aneuploidy in
      carcinogenesis. Tetraploidy is also detected during terminal differentiation and
      represents a hallmark of aging. Most tetraploid cultured cells are arrested by
      p53 stabilization. However, the fate of tetraploid cells in vivo remains largely
      unknown. Here, we analyze the ability to repair wounds in the skin of
      phosphovimentin-deficient (VIM(SA/SA)) mice. Early into wound healing,
      subcutaneous fibroblasts failed to undergo cytokinesis, resulting in binucleate
      tetraploidy. Accordingly, the mRNA level of p21 (a p53-responsive gene) was
      elevated in a VIM(SA/SA)-specific manner. Disappearance of tetraploidy coincided
      with an increase in aneuploidy. Thereafter, senescence-related markers were
      significantly elevated in VIM(SA/SA) mice. Because our tetraploidy-prone mouse
      model also exhibited subcutaneous fat loss at the age of 14 months, another
      premature aging phenotype, our data suggest that following cytokinetic failure, a
      subset of tetraploid cells enters a new cell cycle and develops into aneuploid
      cells in vivo, which promote premature aging. 

PMID- 25847237
TI  - Mycobacterium tuberculosis TlyA Protein Negatively Regulates T Helper (Th) 1 and
      Th17 Differentiation and Promotes Tuberculosis Pathogenesis.
AB  - Mycobacterium tuberculosis, the causative agent of tuberculosis, is an ancient
      pathogen and a major cause of death worldwide. Although various virulence factors
      of M. tuberculosis have been identified, its pathogenesis remains incompletely
      understood. TlyA is a virulence factor in several bacterial infections and is
      evolutionarily conserved in many Gram-positive bacteria, but its function in M.
      tuberculosis pathogenesis has not been elucidated. Here, we report that TlyA
      significantly contributes to the pathogenesis of M. tuberculosis. We show that a
      TlyA mutant M. tuberculosis strain induces increased IL-12 and reduced IL-1beta
      and IL-10 cytokine responses, which sharply contrasts with the immune responses
      induced by wild type M. tuberculosis. Furthermore, compared with wild type M.
      tuberculosis, TlyA-deficient M. tuberculosis bacteria are more susceptible to
      autophagy in macrophages. Consequently, animals infected with the TlyA mutant M.
      tuberculosis organisms exhibited increased host-protective immune responses,
      reduced bacillary load, and increased survival compared with animals infected
      with wild type M. tuberculosis. Thus, M. tuberculosis employs TlyA as a host
      evasion factor, thereby contributing to its virulence. 

PMID- 25847238
TI  - Hepatic serum amyloid A1 aggravates T cell-mediated hepatitis by inducing
      chemokines via Toll-like receptor 2 in mice.
AB  - Serum amyloid A is a proinflammatory molecule that induces leukocyte infiltration
      and promotes neutrophil adhesion to endothelial cells under inflammatory
      conditions. The aim of this study was to examine whether Saa1 aggravates T cell
      mediated hepatitis by inducing chemokines in a liver-specific, Saa1
      overexpressing, transgenic (TG) mouse model. We generated TG mice in which Saa1
      was overexpressed specifically in liver tissue. The chemokines monocyte
      chemotactic protein 1 (MCP1), MIP1alpha, MIP1beta, interferon gamma-induced
      protein 10 (IP-10), and eotaxin were induced in Saa1 TG mice. After concanavalin
      A treatment, Saa1 expression was higher in Saa1 TG mice than in WT mice. More
      severe liver injury, increased hepatocyte apoptosis, and higher levels of hepatic
      enzymes were observed in Saa1 TG mice than in WT mice. Liver infiltration of
      CD4(+) T cells and macrophages increased after inducing hepatitis. Activation of
      T cells was higher in Saa1 TG mice than in WT mice, and the populations of Th17
      cells and regulatory T cells were altered by overexpressing Saa1 in TG mice.
      Secretion of various cytokines, such as interferon gamma, tumor necrosis factor
      alpha, and interleukin 6, increased in Saa1 TG mice. Injecting a Toll-like
      receptor 2 (TLR2) antagonist in vivo inhibited chemokine expression and
      IkappaBalpha phosphorylation and showed that the induction of chemokines by Saa1
      was dependent on TLR2. Hepatic Saa1 accelerated T cell-mediated hepatitis by
      inducing chemokine production and activating T cells by TLR2. Therefore, Saa1
      might be a novel inflammatory factor that acts as a chemokine modulator in
      hepatitis. 

PMID- 25847240
TI  - Abscisic acid transport in human erythrocytes.
AB  - Abscisic acid (ABA) is a plant hormone involved in the response to environmental
      stress. Recently, ABA has been shown to be present and active also in mammals,
      where it stimulates the functional activity of innate immune cells, of
      mesenchymal and hemopoietic stem cells, and insulin-releasing pancreatic beta
      cells. LANCL2, the ABA receptor in mammalian cells, is a peripheral membrane
      protein that localizes at the intracellular side of the plasma membrane. Here we
      investigated the mechanism enabling ABA transport across the plasmamembrane of
      human red blood cells (RBC). Both influx and efflux of [(3)H]ABA occur across
      intact RBC, as detected by radiometric and chromatographic methods. ABA binds
      specifically to Band 3 (the RBC anion transporter), as determined by labeling of
      RBC membranes with biotinylated ABA. Proteoliposomes reconstituted with human
      purified Band 3 transport [(3)H]ABA and [(35)S]sulfate, and ABA transport is
      sensitive to the specific Band 3 inhibitor 4,4'-diisothiocyanostilbene-2,2'
      disulfonic acid. Once inside RBC, ABA stimulates ATP release through the LANCL2
      mediated activation of adenylate cyclase. As ATP released from RBC is known to
      exert a vasodilator response, these results suggest a role for plasma ABA in the
      regulation of vascular tone. 

PMID- 25847239
TI  - PRMT1 Is a Novel Regulator of Epithelial-Mesenchymal-Transition in Non-small Cell
      Lung Cancer.
AB  - Protein arginine methyl transferase 1 (PRMT1) was shown to be up-regulated in
      cancers and important for cancer cell proliferation. However, the role of PRMT1
      in lung cancer progression and metastasis remains incompletely understood. In the
      present study, we show that PRMT1 is an important regulator of epithelial
      mesenchymal transition (EMT), cancer cell migration, and invasion, which are
      essential processes during cancer progression, and metastasis. Additionally, we
      have identified Twist1, a basic helix-loop-helix transcription factor and a well
      known E-cadherin repressor, as a novel PRMT1 substrate. Taken together, we show
      that PRMT1 is a novel regulator of EMT and arginine 34 (Arg-34) methylation of
      Twist1 as a unique "methyl arginine mark" for active E-cadherin repression.
      Therefore, targeting PRMT1-mediated Twist1 methylation might represent a novel
      strategy for developing new anti-invasive/anti-metastatic drugs. Moreover,
      methylated Twist1 (Arg-34), as such, could also emerge as a potential important
      biomarker for lung cancer. 

PMID- 25847241
TI  - Th2 Cytokines Augment IL-31/IL-31RA Interactions via STAT6-dependent IL-31RA
      Expression.
AB  - Interleukin 31 receptor alpha (IL-31RA) is a novel Type I cytokine receptor that
      pairs with oncostatin M receptor to mediate IL-31 signaling. Binding of IL-31 to
      its receptor results in the phosphorylation and activation of STATs, MAPK, and
      JNK signaling pathways. IL-31 plays a pathogenic role in tissue inflammation,
      particularly in allergic diseases. Recent studies demonstrate IL-31RA expression
      and signaling in non-hematopoietic cells, but this receptor is poorly studied in
      immune cells. Macrophages are key immune-effector cells that play a critical role
      in Th2-cytokine-mediated allergic diseases. Here, we demonstrate that Th2
      cytokines IL-4 and IL-13 are capable of up-regulating IL-31RA expression on both
      peritoneal and bone marrow-derived macrophages from mice. Our data also
      demonstrate that IL-4Ralpha-driven IL-31RA expression is STAT6 dependent in
      macrophages. Notably, the inflammation-associated genes Fizz1 and serum amyloid A
      (SAA) are significantly up-regulated in M2 macrophages stimulated with IL-31, but
      not in IL-4 receptor-deficient macrophages. Furthermore, the absence of Type II
      IL-4 receptor signaling is sufficient to attenuate the expression of IL-31RA in
      vivo during allergic asthma induced by soluble egg antigen, which may suggest a
      role for IL-31 signaling in Th2 cytokine-driven inflammation and allergic
      responses. Our study reveals an important counter-regulatory role between Th2
      cytokine and IL-31 signaling involved in allergic diseases. 

PMID- 25847242
TI  - X-ray and Cryo-electron Microscopy Structures of Monalysin Pore-forming Toxin
      Reveal Multimerization of the Pro-form.
AB  - beta-Barrel pore-forming toxins (beta-PFT), a large family of bacterial toxins,
      are generally secreted as water-soluble monomers and can form oligomeric pores in
      membranes following proteolytic cleavage and interaction with cell surface
      receptors. Monalysin has been recently identified as a beta-PFT that contributes
      to the virulence of Pseudomonas entomophila against Drosophila. It is secreted as
      a pro-protein that becomes active upon cleavage. Here we report the crystal and
      cryo-electron microscopy structure of the pro-form of Monalysin as well as the
      crystal structures of the cleaved form and of an inactive mutant lacking the
      membrane-spanning region. The overall structure of Monalysin displays an
      elongated shape, which resembles those of beta-pore-forming toxins, such as
      Aerolysin, but is devoid of a receptor-binding domain. X-ray crystallography,
      cryo-electron microscopy, and light-scattering studies show that pro-Monalysin
      forms a stable doughnut-like 18-mer complex composed of two disk-shaped nonamers
      held together by N-terminal swapping of the pro-peptides. This observation is in
      contrast with the monomeric pro-form of the other beta-PFTs that are receptor
      dependent for membrane interaction. The membrane-spanning region of pro-Monalysin
      is fully buried in the center of the doughnut, suggesting that upon cleavage of
      pro-peptides, the two disk-shaped nonamers can, and have to, dissociate to leave
      the transmembrane segments free to deploy and lead to pore formation. In contrast
      with other toxins, the delivery of 18 subunits at once, nearby the cell surface,
      may be used to bypass the requirement of receptor-dependent concentration to
      reach the threshold for oligomerization into the pore-forming complex. 

PMID- 25847243
TI  - Baicalin inhibits the lethality of ricin in mice by inducing protein
      oligomerization.
AB  - Toxic ribosome-inactivating proteins abolish cell viability by inhibiting protein
      synthesis. Ricin, a member of these lethal proteins, is a potential bioterrorism
      agent. Despite the grave challenge posed by these toxins to public health, post
      exposure treatment for intoxication caused by these agents currently is
      unavailable. In this study, we report the identification of baicalin extracted
      from Chinese herbal medicine as a compound capable of inhibiting the activity of
      ricin. More importantly, post-exposure treatment with baicalin significantly
      increased the survival of mice poisoned by ricin. We determined the mechanism of
      action of baicalin by solving the crystal structure of its complex with the A
      chain of ricin (RTA) at 2.2 A resolution, which revealed that baicalin interacts
      with two RTA molecules at a novel binding site by hydrogen bond networks and
      electrostatic force interactions, suggesting its role as molecular glue of the
      RTA. Further biochemical and biophysical analyses validated the amino acids
      directly involved in binding the inhibitor, which is consistent with the
      hypothesis that baicalin exerts its inhibitory effects by inducing RTA to form
      oligomers in solution, a mechanism that is distinctly different from previously
      reported inhibitors. This work offers promising leads for the development of
      therapeutics against ricin and probably other ribosome-inactivating proteins. 

PMID- 25847244
TI  - Histone Chaperone HIRA in Regulation of Transcription Factor RUNX1.
AB  - RUNX1 (Runt-related transcription factor 1) is indispensable for the generation
      of hemogenic endothelium. However, the regulation of RUNX1 during this
      developmental process is poorly understood. We investigated the role of the
      histone chaperone HIRA (histone cell cycle regulation-defective homolog A) from
      this perspective and report that HIRA significantly contributes toward the
      regulation of RUNX1 in the transition of differentiating mouse embryonic stem
      cells from hemogenic to hematopoietic stage. Direct interaction of HIRA and RUNX1
      activates the downstream targets of RUNX1 implicated in generation of
      hematopoietic stem cells. At the molecular level, HIRA-mediated incorporation of
      histone H3.3 variant within the Runx1 +24 mouse conserved noncoding element is
      essential for the expression of Runx1 during endothelial to hematopoietic
      transition. An inactive chromatin at the intronic enhancer of Runx1 in absence of
      HIRA significantly repressed the transition of cells from hemogenic to
      hematopoietic fate. We expect that the HIRA-RUNX1 axis might open up a novel
      approach in understanding leukemogenesis in future. 

PMID- 25847245
TI  - Two duplicated genes DDI2 and DDI3 in budding yeast encode a cyanamide hydratase
      and are induced by cyanamide.
AB  - Two DNA damage-inducible genes in Saccharomyces cerevisiae, DDI2 and DDI3, are
      identical and encode putative HD domain-containing proteins, whose functions are
      currently unknown. Because Ddi2/3 also shows limited homology to a fungal
      cyanamide hydratase that converts cyanamide to urea, we tested the enzymatic
      activity of recombinant Ddi2. To this end, we developed a novel enzymatic assay
      and determined that the Km value of the recombinant Ddi2/3 for cyanamide is 17.3
      +/- 0.05 mm, and its activity requires conserved residues in the HD domain.
      Unlike most other DNA damage-inducible genes, DDI2/3 is only induced by a
      specific set of alkylating agents and surprisingly is strongly induced by
      cyanamide. To characterize the biological function of DDI2/3, we sequentially
      deleted both DDI genes and found that the double mutant was unable to metabolize
      cyanamide and became much more sensitive to growth inhibition by cyanamide,
      suggesting that the DDI2/3 genes protect host cells from cyanamide toxicity.
      Despite the physiological relevance of the cyanamide induction, DDI2/3 is not
      involved in its own transcriptional regulation. The significance of cyanamide
      hydratase activity and its induced expression is discussed. 

PMID- 25847246
TI  - Association of MMP7 -181A->G Promoter Polymorphism with Gastric Cancer Risk:
      INFLUENCE OF NICOTINE IN DIFFERENTIAL ALLELE-SPECIFIC TRANSCRIPTION VIA INCREASED
      PHOSPHORYLATION OF cAMP-RESPONSE ELEMENT-BINDING PROTEIN (CREB).
AB  - Elevated expression of matrix metalloproteinase7 (MMP7) has been demonstrated to
      play a pivotal role in cancer invasion. The -181A->G (rs11568818) polymorphism in
      the MMP7 promoter modulates gene expression and possibly affects cancer
      progression. Here, we evaluated the impact of -181A->G polymorphism on MMP7
      promoter activity and its association with gastric cancer risk in eastern Indian
      case-control cohorts (n = 520). The GG genotype as compared with the AA genotype
      was predisposed (p = 0.02; odds ratio = 1.9, 95% confidence interval = 1.1-3.3)
      to gastric cancer risk. Stratification analysis showed that tobacco addiction
      enhanced gastric cancer risk in GG subjects when compared with AA subjects (p =
      0.03, odds ratio = 2.46, and 95% confidence interval = 1.07-5.68). Meta-analysis
      revealed that tobacco enhanced the risk for cancer more markedly in AG and GG
      carriers. Activity and expression of MMP7 were significantly higher in GG than in
      AA carriers. In support, MMP7 promoter-reporter assays showed greater
      transcriptional activity toward A to G transition under basal/nicotine
      induced/cAMP-response element-binding protein (CREB) overexpressed conditions in
      gastric adenocarcinoma cells. Moreover, nicotine (a major component of tobacco)
      treatment significantly up-regulated MMP7 expression due to enhanced CREB
      phosphorylation followed by its nuclear translocation in gastric adenocarcinoma
      cells. Furthermore, chromatin immunoprecipitation experiments revealed higher
      binding of phosphorylated CREB with the -181G than the -181A allele. Altogether,
      specific binding of phosphorylated CREB to the G allele-carrying promoter
      enhances MMP7 gene expression that is further augmented by nicotine due to
      increased CREB phosphorylation and thereby increases the risk for gastric cancer.

PMID- 25847247
TI  - Crucial genes and pathways in chicken germ stem cell differentiation.
AB  - Male germ cell differentiation is a subtle and complex regulatory process.
      Currently, its regulatory mechanism is still not fully understood. In our
      experiment, we performed the first comprehensive genome and transcriptome-wide
      analyses of the crucial genes and signaling pathways in three kinds of crucial
      cells (embryonic stem cells, primordial germ cell, and spermatogonial stem cells)
      that are associated with the male germ cell differentiation. We identified
      thousands of differentially expressed genes in this process, and from these we
      chose 173 candidate genes, of which 98 genes were involved in cell
      differentiation, 19 were involved in the metabolic process, and 56 were involved
      in the differentiation and metabolic processes, like GAL9, AMH, PLK1, and PSMD7
      and so on. In addition, we found that 18 key signaling pathways were involved
      mainly in cell proliferation, differentiation, and signal transduction processes
      like TGF-beta, Notch, and Jak-STAT. Further exploration found that the candidate
      gene expression patterns were the same between in vitro induction experiments and
      transcriptome results. Our results yield clues to the mechanistic basis of male
      germ cell differentiation and provide an important reference for further studies.

PMID- 25847248
TI  - Crystal Structure of the Human Pol alpha B Subunit in Complex with the C-terminal
      Domain of the Catalytic Subunit.
AB  - In eukaryotic DNA replication, short RNA-DNA hybrid primers synthesized by
      primase-DNA polymerase alpha (Prim-Pol alpha) are needed to start DNA replication
      by the replicative DNA polymerases, Pol delta and Pol epsilon. The C terminus of
      the Pol alpha catalytic subunit (p180C) in complex with the B subunit (p70)
      regulates the RNA priming and DNA polymerizing activities of Prim-Pol alpha. It
      tethers Pol alpha and primase, facilitating RNA primer handover from primase to
      Pol alpha. To understand these regulatory mechanisms and to reveal the details of
      human Pol alpha organization, we determined the crystal structure of p70 in
      complex with p180C. The structured portion of p70 includes a phosphodiesterase
      (PDE) domain and an oligonucleotide/oligosaccharide binding (OB) domain. The N
      terminal domain and the linker connecting it to the PDE domain are disordered in
      the reported crystal structure. The p180C adopts an elongated asymmetric saddle
      shape, with a three-helix bundle in the middle and zinc-binding modules (Zn1 and
      Zn2) on each side. The extensive p180C-p70 interactions involve 20 hydrogen bonds
      and a number of hydrophobic interactions resulting in an extended buried surface
      of 4080 A(2). Importantly, in the structure of the p180C-p70 complex with full
      length p70, the residues from the N-terminal to the OB domain contribute to
      interactions with p180C. The comparative structural analysis revealed both the
      conserved features and the differences between the human and yeast Pol alpha
      complexes. 

PMID- 25847249
TI  - In Silico Modeling-based Identification of Glucose Transporter 4 (GLUT4)
      selective Inhibitors for Cancer Therapy.
AB  - Tumor cells rely on elevated glucose consumption and metabolism for survival and
      proliferation. Glucose transporters mediating glucose entry are key proximal rate
      limiting checkpoints. Unlike GLUT1 that is highly expressed in cancer and more
      ubiquitously expressed in normal tissues, GLUT4 exhibits more limited normal
      expression profiles. We have previously determined that insulin-responsive GLUT4
      is constitutively localized on the plasma membrane of myeloma cells.
      Consequently, suppression of GLUT4 or inhibition of glucose transport with the
      HIV protease inhibitor ritonavir elicited growth arrest and/or apoptosis in
      multiple myeloma. GLUT4 inhibition also caused sensitization to metformin in
      multiple myeloma and chronic lymphocytic leukemia and a number of solid tumors
      suggesting the broader therapeutic utility of targeting GLUT4. This study sought
      to identify selective inhibitors of GLUT4 to develop a more potent cancer
      chemotherapeutic with fewer potential off-target effects. Recently, the crystal
      structure of GLUT1 in an inward open conformation was reported. Although this is
      an important achievement, a full understanding of the structural biology of
      facilitative glucose transport remains elusive. To date, there is no three
      dimensional structure for GLUT4. We have generated a homology model for GLUT4
      that we utilized to screen for drug-like compounds from a library of 18 million
      compounds. Despite 68% homology between GLUT1 and GLUT4, our virtual screen
      identified two potent compounds that were shown to target GLUT4 preferentially
      over GLUT1 and block glucose transport. Our results strongly bolster the utility
      of developing GLUT4-selective inhibitors as anti-cancer therapeutics. 

PMID- 25847250
TI  - Formation and decay of the arrestin.rhodopsin complex in native disc membranes.
AB  - In the G protein-coupled receptor rhodopsin, light-induced cis/trans
      isomerization of the retinal ligand triggers a series of distinct receptor states
      culminating in the active Metarhodopsin II (Meta II) state, which binds and
      activates the G protein transducin (Gt). Long before Meta II decays into the
      aporeceptor opsin and free all-trans-retinal, its signaling is quenched by
      receptor phosphorylation and binding of the protein arrestin-1, which blocks
      further access of Gt to Meta II. Although recent crystal structures of arrestin
      indicate how it might look in a precomplex with the phosphorylated receptor, the
      transition into the high affinity complex is not understood. Here we applied
      Fourier transform infrared spectroscopy to monitor the interaction of arrestin-1
      and phosphorylated rhodopsin in native disc membranes. By isolating the unique
      infrared signature of arrestin binding, we directly observed the structural
      alterations in both reaction partners. In the high affinity complex, rhodopsin
      adopts a structure similar to Gt-bound Meta II. In arrestin, a modest loss of
      beta-sheet structure indicates an increase in flexibility but is inconsistent
      with a large scale structural change. During Meta II decay, the arrestin
      rhodopsin stoichiometry shifts from 1:1 to 1:2. Arrestin stabilizes half of the
      receptor population in a specific Meta II protein conformation, whereas the other
      half decays to inactive opsin. Altogether these results illustrate the distinct
      binding modes used by arrestin to interact with different functional forms of the
      receptor. 

PMID- 25847252
TI  - Ex vivo evaluation of the effect of photodynamic therapy on skin scars and striae
      distensae.
AB  - BACKGROUND: Skin scars and striae distensae (SD) are common dermal disorders with
      ill-defined treatment options. There is emerging clinical evidence for use of
      photodynamic therapy (PDT) in treating skin fibrosis. Therefore, the aim here was
      to investigate the effect of PDT on skin scars and SD in an ex vivo model of
      human skin scarring. METHODS: Photodynamic therapy, with 5ALA or MALA in addition
      to illumination with 40 J/cm(2) of red light, was applied to striae alba, fine
      line, hypertrophic and keloid scars ex vivo (n = 18). General morphology was
      assessed by H&E, Herovici's and Weigert's differential staining. Apoptosis,
      proliferation, metalloproteinase 3 and tropoelastin expression were quantified
      immunohistochemically, and differential gene expression of proliferating cell
      nuclear antigen (PCNA), collagen (COL) type I and type III, matrix
      metalloproteinase 3 (MMP3) and tropoelastin (ELN) was assessed by real-time
      quantitative reverse transcription polymerase chain reaction. RESULTS: Apoptosis
      increased, which correlated with decreased proliferation and PCNA gene
      expression. Post-PDT, matrix components were found to be re-organised in both
      hypertrophic and keloid scars. COLI and COLIII gene expression levels decreased,
      whilst MMP3 and ELN increased significantly post-PDT compared to normal skin and
      untreated controls (P < 0.05). However, no significant difference between 5ALA
      and MALA-PDT treatments was observed. CONCLUSION: Using our unique ex vivo model,
      we show for the first time morphological and cellular effect of application of
      PDT, which correlates with the degree and severity of dermal fibrosis. In view of
      this, PDT may be ideal in targeting treatment of abnormal skin scarring.

PMID- 25847253
TI  - Epigallocatechin gallate stimulates the neuroreactive salivary secretomotor
      system in autoimmune sialadenitis of MRL-Fas(lpr) mice via activation of cAMP
      dependent protein kinase A and inactivation of nuclear factor kappaB.
AB  - The water channel aquaporin 5 (AQP5) plays a crucial role in regulating salivary
      flow rates. Xerostomia is often observed in patients with Sjogren's syndrome, and
      this is attributed to reduced AQP5 expression in the salivary glands. Recently,
      anti-type 3 muscarinic cholinergic receptors (M3R) autoantibodies and nuclear
      factor kappaB (NF-kappaB) have been found to be negative regulators of AQP5
      expression in the salivary gland. Anti-M3R autoantibodies desensitize M3R to
      salivary secretagogues in Sjogren's syndrome, while activated NF-kappaB
      translocates to nuclei and binds to the AQP5 gene promoter, resulting in the
      suppression of AQP5 expression. We previously documented that epigallocatechin
      gallate (EGCG), which is a robust antioxidant contained in green tea, ameliorates
      oxidative stress-induced tissue damage to the salivary glands of MRL/MpJ-lpr/lpr
      (MRL-Fas(lpr)) mice, which are widely used as a model of Sjogren's syndrome.
      Reactive oxygen species (ROS) can activate NF-kappaB and inactivate protein
      kinase A (PKA), which is a key driver of AQP5 expression. In this study, we
      examined the effects of administering EGCG to MRL-Fas(lpr) mice with autoimmune
      sialadenitis on the levels of AQP5, activated NF-kappaB p65 subunit, activated
      PKA, activated c-Jun N-terminal kinase (JNK) (an activator of NF-kappaB),
      inhibitor kappaB (IkappaB) and histone deacetylase 1 (HDAC1) (an inhibitor of NF
      kappaB). In EGCG-treated mice, intense aster-like immunostaining for AQP5 was
      observed on the apical plasma membranes (APMs) of submandibular gland acinar
      cells. Likewise, PKA, IkappaB and HDAC1 were highly expressed in salivary gland
      tissues, whereas the expression of JNK and NF-kappaB p65 was negligible. Rank
      correlation and partial correlation analyses revealed that treatment with EGCG
      upregulated AQP5 expression on the APM of acinar cells through activation of PKA
      and inactivation of NF-kappaB, while IkappaB and HDAC1 played a pivotal role in
      the induction of AQP5 expression by PKA. Our study indicates that EGCG may have
      therapeutic potential for Sjogren's syndrome patients. 

PMID- 25847251
TI  - Diaminopimelic Acid Amidation in Corynebacteriales: NEW INSIGHTS INTO THE ROLE OF
      LtsA IN PEPTIDOGLYCAN MODIFICATION.
AB  - A gene named ltsA was earlier identified in Rhodococcus and Corynebacterium
      species while screening for mutations leading to increased cell susceptibility to
      lysozyme. The encoded protein belonged to a huge family of glutamine
      amidotransferases whose members catalyze amide nitrogen transfer from glutamine
      to various specific acceptor substrates. We here describe detailed physiological
      and biochemical investigations demonstrating the specific role of LtsA protein
      from Corynebacterium glutamicum (LtsACg) in the modification by amidation of cell
      wall peptidoglycan diaminopimelic acid (DAP) residues. A morphologically altered
      but viable DeltaltsA mutant was generated, which displays a high susceptibility
      to lysozyme and beta-lactam antibiotics. Analysis of its peptidoglycan structure
      revealed a total loss of DAP amidation, a modification that was found in 80% of
      DAP residues in the wild-type polymer. The cell peptidoglycan content and cross
      linking were otherwise not modified in the mutant. Heterologous expression of
      LtsACg in Escherichia coli yielded a massive and toxic incorporation of amidated
      DAP into the peptidoglycan that ultimately led to cell lysis. In vitro assays
      confirmed the amidotransferase activity of LtsACg and showed that this enzyme
      used the peptidoglycan lipid intermediates I and II but not, or only marginally,
      the UDP-MurNAc pentapeptide nucleotide precursor as acceptor substrates. As is
      generally the case for glutamine amidotransferases, either glutamine or NH4(+)
      could serve as the donor substrate for LtsACg. The enzyme did not amidate
      tripeptide- and tetrapeptide-truncated versions of lipid I, indicating a strict
      specificity for a pentapeptide chain length.

PMID- 25847254
TI  - Effect of the Acidic Dental Resin Monomer 10-methacryloyloxydecyl Dihydrogen
      Phosphate on Odontoblastic Differentiation of Human Dental Pulp Cells.
AB  - Although 10-methacryloyloxydecyl dihydrogen phosphate (10-MDP) is frequently used
      as an acidic resin monomer in dental adhesives, its effect on dental pulp cells
      (DPCs) has been rarely reported. The purpose of this study was to examine the
      effects of 10-MDP on the inflammatory response and odontoblastic differentiation
      of DPCs at minimally toxic concentrations. We found that 10-MDP caused the
      release of inflammatory cytokines including NO, PGE2, iNOS, COX-2, TNF-alpha, IL
      1beta, IL-6 and IL-8 in a concentration-dependent manner. In addition, 10-MDP
      reduced alkaline phosphatase activity, mineralization nodule formation and mRNA
      expression of odontoblastic differentiation markers such as dentin
      sialophosphoprotein, dentin matrix protein-1, osterix and Runx2 in a
      concentration-dependent manner with low toxicity. In addition, 10-MDP induced
      activation of nuclear factor-E2-related factor 2 (Nrf2) and its target gene,
      haeme oxygenase-1 (HO-1). We evaluated whether the effect of 10-MDP was related
      to the induction of HO-1 and found that treatment with a selective inhibitor of
      HO-1 reversed the production of 10-MDP-mediated pro-inflammatory cytokines and
      the inhibition of differentiation markers. Pre-treatment with either a GSH
      synthesis inhibitor or antioxidants blocked 10-MDP-induced mitogen-activated
      protein kinases (MAPKs), Nrf2 and NF-kappaB pathways. Taken together, the results
      of this study showed that minimally toxic concentrations of 10-MDP promoted an
      inflammatory response and suppressed odontoblastic differentiation of DPCs by
      activating Nrf2-mediated HO-1 induction through MAPK and NF-kappaB signalling. 

PMID- 25847260
TI  - Inhibition of expression of hepatitis C virus 1b genotype core and NS4B genes in
      HepG2 cells using artificial microRNAs.
AB  - The present study aimed to evaluate the silencing effect of artificial microRNAs
      (amiRNAs) against the hepatitis C virus (HCV) 1b (HCV1b) genotype core (C) and
      non-structural protein 4B (NS4B) genes. pDsRed-monomer-Core and pDsRed-monomer
      NS4B plasmids, containing the target genes were constructed. A total of eight
      artificial micro RNA (amiRNA)-expressing plasmids, namely, pmiRE-C-mi1 to -mi4
      and pmiRE-NS4B-mi1 to -mi4, were designed and constructed to interfere with
      various sites of the core and NS4B genes, and the amiRNA interfering plasmid and
      the corresponding target gene-expressing plasmid were co-transfected into HepG2
      cells. At 48 h after transfection, HCV core and NS4B gene expression levels were
      detected using fluorescence microscopy, flow cytometry, reverse transcription
      quantitative polymerase chain reaction and western blot analysis. Fluorescence
      microscopy revealed that the target gene-transfected cells expressed red
      fluorescent protein, whereas the interfering plasmid-transfected cells exhibited
      expression of green fluorescent protein. The percentage of red fluorescent
      proteins and mean fluorescence intensity, as well as protein expression levels of
      the core and NS4B genes within the cells, which were co-transfected by the amiRNA
      interfering plasmid and the target gene, were significantly decreased. The
      results of the present study confirmed that amiRNAs may effectively and
      specifically inhibit the expression of HCV1b core and NS4B genes in HepG2 cells,
      potentially providing a novel therapeutic strategy for the treatment of HCV.

PMID- 25847261
TI  - A type of novel fluorescent magnetic carbon quantum dots for cells imaging and
      detection.
AB  - A new type of multifunctional fluorescent magnetic carbon quantum dots
      SPIO@CQDs(n) ([superparamagnetic iron oxide nanoparticles (SPIO), carbon quantum
      dots, (CQDs)]) with magnetic and fluorescence properties was designed and
      prepared through layer-by-layer self-assembly method. The as-synthesized
      SPIO@CQDs(n) exhibited different emission colors including blue, green, and red
      when they were excited at different excitation wavelengths, and its fluorescent
      intensity increased as the increase of CQD layer (n). SPIO@CQDs(n) with quite low
      toxicity could mark cytoplasm with fluorescence by means of nonimmune markers.
      The mixture sample of liver cells L02 and hepatoma carcinoma cells HepG2 was
      taken as an example, and HepG2 cells were successfully separated and detected
      effectively by SPIO@CQDs(n), with a separation rate of 90.31%. Importantly, the
      designed and prepared SPIO@CQDs( n ) are certified to be wonderful biological
      imaging and magnetic separation regents.

PMID- 25847262
TI  - Diagnosis of congenital Trypanosoma cruzi infection: A serologic test using Shed
      Acute Phase Antigen (SAPA) in mother-child binomial samples.
AB  - Chagas congenital infection is an important health problem in endemic and non
      endemic areas in which Trypanosoma cruzi-infected women can transmit the parasite
      to their offspring. In this study, we evaluated the antibody levels against the
      T. cruzi Shed Acute Phase Antigen (SAPA) in 91 binomial samples of seropositive
      pregnant women and their infected and non-infected children by ELISA. In 70
      children without congenital T. cruzi transmission, the titers of anti-SAPA
      antibodies were lower than those of their seropositive mothers. In contrast,
      90.5% of 21 congenitally infected children, at around 1 month of age, showed
      higher anti-SAPA antibody levels than their mothers. Subtracting the SAPA-ELISA
      mother OD value to the SAPA-ELISA child OD allowed efficient detection of most T.
      cruzi congenitally infected children immediately after birth, when total anti
      parasite antibodies transferred during pregnancy are still present in all
      children born to seropositive women. A positive correlation was observed between
      parasitemia levels in mothers and infants evaluated by quantitative DNA
      amplification and anti-SAPA antibody titers by ELISA. As SAPA serology has proved
      to be very efficient to detect T. cruzi infection in mother-child binomial
      samples, it could be of extreme help for early diagnosis of newborns, in
      maternities and hospitals where DNA amplification is not available. This prompt
      diagnosis may prevent drop out of the long-term follow-up for future diagnosis
      and may ensure early trypanocidal treatment, which has proved to be efficient to
      cure infants with congenital Chagas disease. 

PMID- 25847263
TI  - When private actors matter: Information-sharing network and surveillance of
      Highly Pathogenic Avian Influenza in Vietnam.
AB  - The effectiveness of animal health surveillance systems depends on their capacity
      to gather sanitary information from the animal production sector. In order to
      assess this capacity we analyzed the flow of sanitary information regarding
      Highly Pathogenic Avian Influenza (HPAI) suspicions in poultry in Vietnam.
      Participatory methods were applied to assess the type of actors and likelihood of
      information sharing between actors in case of HPAI suspicion in poultry. While
      the reporting of HPAI suspicions is mandatory, private actors had more access to
      information than public actors. Actors of the upstream sector (medicine and feed
      sellers) played a key role in the diffusion of information. The central role of
      these actors and the influence of the information flow on the adoption by poultry
      production stakeholders of behaviors limiting (e.g. prevention measures) or
      promoting disease transmission (e.g. increased animal movements) should be
      accounted for in the design of surveillance and control programs.

PMID- 25847264
TI  - Noninvasive measurement of aristolochic acid-DNA adducts in urine samples from
      aristolochic acid-treated rats by liquid chromatography coupled tandem mass
      spectrometry: evidence for DNA repair by nucleotide-excision repair mechanisms.
AB  - Nephrotoxic aristolochic acids (AAs) form covalently bonded DNA adducts upon
      metabolic activation. In this work, a non-invasive approach to detect AAs
      exposure by quantifying urinary excreted DNA-AA adducts is presented. The
      developed method entails solid-phase extraction (SPE) enrichment of the urine
      excreted DNA-AAs adducts, addition of internal standard, and quantification by
      liquid chromatography coupled tandem mass spectrometric (LC-MS/MS) analysis.
      Quantitative analysis revealed 7-(deoxyadenosine-N(6)-yl)-aristolactam II and 7
      (deoxyguanosine-N(2)-yl)-aristolactam I that were previously detected as major
      DNA-AA adducts in different organs of AA-dosed rats, were detected as the major
      urine excreted adducts. Lower levels of 7-(deoxyadenosine-N(6)-yl)-aristolactam I
      and 7-(deoxyguanosine-N(2)-yl)-aristolactam II were also detected in the
      collected urine samples. The identities of the detected urinary DNA-AA adducts
      were confirmed by comparing chromatographic retention time with synthetic
      standards, by high-accuracy MS, and MS/MS analyses. LC-MS/MS analysis of the
      urine samples collected from the AAs-dosed rats demonstrated a time-dependent
      decrease in the urinary adduct levels, indicating the urinary DNA-AA adduct
      levels were reflective of the tissue adduct levels. It is expected that the
      developed approach of detecting urinary DNA-AA adducts will facilitate further
      carcinogenesis investigations of AAs. 

PMID- 25847266
TI  - Optimization of the Divergent method for genotyping single nucleotide variations
      using SYBR Green-based single-tube real-time PCR.
AB  - A novel technique, called Divergent, for single-tube real-time PCR genotyping of
      point mutations without the use of fluorescently labeled probes has recently been
      reported. This novel PCR technique utilizes a set of four primers and a
      particular denaturation temperature for simultaneously amplifying two different
      amplicons which extend in opposite directions from the point mutation. The two
      amplicons can readily be detected using the melt curve analysis downstream to a
      closed-tube real-time PCR. In the present study, some critical aspects of the
      original method were specifically addressed to further implement the technique
      for genotyping the DNM1 c.G767T mutation responsible for exercise-induced
      collapse in Labrador retriever dogs. The improved Divergent assay was easily set
      up using a standard two-step real-time PCR protocol. The melting temperature
      difference between the mutated and the wild-type amplicons was approximately 5
      degrees C which could be promptly detected by all the thermal cyclers. The
      upgraded assay yielded accurate results with 157pg of genomic DNA per reaction.
      This optimized technique represents a flexible and inexpensive alternative to the
      minor grove binder fluorescently labeled method and to high resolution melt
      analysis for high-throughput, robust and cheap genotyping of single nucleotide
      variations. 

PMID- 25847265
TI  - Inherited variability in a master regulator polymorphism (rs4846126) associates
      with survival in 5-FU treated colorectal cancer patients.
AB  - BACKGROUND: Treatment with 5-fluorouracil (5-FU) is known to improve survival in
      many cancers including colorectal cancer. Response to the treatment, overall
      survival and recurrence show inter-individual variation. METHODS: In this study
      we employed a strategy to search eQTL variants influencing the expression of a
      large number of genes. We identified four single nucleotide polymorphisms,
      defined as master regulators of transcription, and genotyped them in a set of 218
      colorectal cancer patients undergoing adjuvant 5-FU based therapy. RESULTS: Our
      results showed that the minor allele variant of the rs4846126 polymorphism was
      associated with poor overall and progression-free survival. Patients that were
      homozygous for the variant allele showed an over two fold increased risk of death
      (HR 2.20 95%CI 1.05-4.60) and progression (HR 2.88, 95% 1.47-5.63). The
      integration of external information from publicly available gene expression
      repositories suggested that the rs4846126 polymorphism deserves further
      investigation. This variant potentially regulates the gene expression of 273
      genes with some of them possibly associated to the patient's response to 5-FU
      treatment or colorectal cancer. CONCLUSIONS: Present results show that mining of
      public data repositories in combination with own data can be a fruitful approach
      to identify markers that affect therapy outcome. In particular, a genetic screen
      of master regulators may help in order to search for the polymorphisms involved
      in treatment response in cancer patients.

PMID- 25847267
TI  - Impact of abasic site orientation within nucleosomes on human APE1 endonuclease
      activity.
AB  - Glycosylases responsible for recognizing DNA lesions and initiating Base Excision
      Repair (BER) are impeded by the presence of histones, which are essential for
      compaction of the genetic material in the nucleus. Abasic sites are an abundant
      mutagenic lesion in the DNA, arising spontaneously and as the product of
      glycosylase activity, making it a common intermediate in BER. The
      apurinic/apyrimidinic endonuclease 1 (APE1) recognizes abasic sites and cleaves
      the DNA backbone adjacent to the lesion, creating the single-strand break
      essential for the subsequent steps of BER. In this study the endonuclease
      activity of human APE1 was measured on reconstituted nucleosome core particles
      (NCPs) with DNA containing enzymatically created abasic sites (AP) or the abasic
      site analog tetrahydrofuran (TF) at different rotational positions relative to
      the histone core surface. The presence of histones on the DNA reduced APE1
      activity overall, and the magnitude was greatly influenced by differences in
      orientation of the lesions along the DNA gyre relative to the histone core.
      Abasic moieties oriented with their phosphate backbones adjacent to the
      underlying histones (In) were cleaved less efficiently than those oriented away
      from the histone core (Out) or between the In and Out orientations (Mid). The
      impact on APE1 at each orientation was very similar between the AP and TF
      lesions, highlighting the dependability of the TF abasic analog in APE1 activity
      measurements in nucleosomes. Measurement of APE1 binding to the NCP substrates
      reveals a substantial reduction in its interaction with nucleosomes compared to
      naked DNA, also in a lesion orientation-dependent manner, reinforcing the concept
      that reduction in APE1 activity on nucleosomes is due to occlusion from its
      abasic DNA substrate by the histones. These results suggest that APE1 activity in
      nucleosomes, like BER glycosylases, is primarily regulated by its chance
      interactions with transiently exposed lesions. 

PMID- 25847268
TI  - Acute and chronic administration of gold nanoparticles cause DNA damage in the
      cerebral cortex of adult rats.
AB  - The use of gold nanoparticles is increasing in medicine; however, their toxic
      effects remain to be elucidated. Studies show that gold nanoparticles can cross
      the blood-brain barrier, as well as accumulate in the brain. Therefore, this
      study was undertaken to better understand the effects of gold nanoparticles on
      rat brains. DNA damage parameters were evaluated in the cerebral cortex of adult
      rats submitted to acute and chronic administration of gold nanoparticles of two
      different diameters: 10 and 30nm. During acute administration, adult rats
      received a single intraperitoneal injection of either gold nanoparticles or
      saline solution. During chronic administration, adult rats received a daily
      single injection for 28 days of the same gold nanoparticles or saline solution.
      Twenty-four hours after either single (acute) or last injection (chronic), the
      rats were euthanized by decapitation, their brains removed, and the cerebral
      cortices isolated for evaluation of DNA damage parameters. Our study showed that
      acute administration of gold nanoparticles in adult rats presented higher levels
      of damage frequency and damage index in their DNA compared to the control group.
      It was also observed that gold nanoparticles of 30nm presented higher levels of
      damage frequency and damage index in the DNA compared to the 10nm ones. When
      comparing the effects of chronic administration of gold nanoparticles of 10 and
      30nm, we observed that occurred significant different index and frequency damage,
      comparing with control group. However, there is no difference between the 10 and
      30nm groups in the levels of DNA damage for both parameters of the Comet assay.
      Results suggest that gold nanoparticles for both sizes cause DNA damage for
      chronic as well as acute treatments, although a higher damage was observed for
      the chronic one. 

PMID- 25847269
TI  - Expression and methylation of DNA repair genes in lens epithelium cells of age
      related cataract.
AB  - The development of age-related cataract (ARC) is associated with DNA damage of
      the lens epithelial cells (LECs). This study aimed to investigate the expression
      level of DNA repair genes in LECs of ARC and examine whether any altered
      expression observed could result from DNA methylation of the promoter region of
      the genes. The expression levels of DNA repair genes were evaluated by microarray
      analysis. The results were further confirmed by qRT-PCR. DNA methylation of genes
      with altered expression was determined by bisulfite-specific (BSP) PCR. The mRNA
      levels of 10 DNA repair genes were decreased and the level of 1 DNA repair gene
      was increased in LECs of ARC patients compared with controls. The promoter region
      of the MGMT gene was hypermethylated in ARC tissue compared to controls. The data
      provide evidence that altered expression of DNA repair genes is associated with
      pathogenesis of ARC. DNA methylation of MGMT may regulate the expression of the
      gene and be involved in the development of ARC. 

PMID- 25847270
TI  - Functional characterization of genetic polymorphisms in the H2AFX distal
      promoter.
AB  - Due to the critical role of the H2AX histone variant in double-strand break
      repair, genetic variants in the H2AX gene, H2AFX, may influence cancer
      susceptibility. Genetic association studies have correlated H2AFX upstream
      variants with cancer risk; however it is unclear if any are causal. H2AFX has at
      least two alternate transcripts that encode the same reading frame; a short 0.6kb
      transcript that lacks an intron or poly-A tail and is predicted to be highly
      expressed during the replication stage of the cell cycle, and a long 1.6kb poly-A
      tailed transcript that is expressed in a replication-independent manner. To
      examine the functional impact of the rs643788, rs8551, rs7759, and rs2509049
      upstream variants, we characterized their influence on gene expression, cell
      survival after DNA assault, and transcription factor binding. Analysis of allelic
      imbalance using quantitative sequencing of cDNA from lymphoblast cell lines did
      not reveal any difference in expression of the 1.6kb polyadenylated transcript
      between the common H2AFX upstream haplotypes. We did, however, identify a
      previously unreported 197 base pair intron in the H2AFX 3'untranslated region
      that appears to be present regardless of haplotype. Assessment of cell survival
      after irradiation treatment did not show any difference in survival between cell
      lines of different haplotypes. Gel shift assays revealed that the rs643788 C
      allele disrupts YY1 transcription factor binding and the rs2509049 C allele binds
      more strongly to a protein complex than does the rs2509049 T allele. Though we
      did not identify any differences in expression or survival between haplotypes,
      differential protein binding at two of the polymorphisms suggests further
      functional analyses may reveal a role for these variants in influencing gene
      expression at specific points of the cell cycle or in specific tissues. 

PMID- 25847271
TI  - Ethyl methanesulfonate induces mutations in Caenorhabditis elegans embryos at a
      high frequency.
AB  - Mutagenesis protocols typically call for exposure of late-stage larvae or adults
      to a mutagen with the intention of inducing mutations in a robust germ line.
      Instead, ca. 16,000 CB665 [unc-58(e665)] one- to four-cell embryos of the
      nematode Caenorhabditis elegans were hand selected and exposed to ethyl
      methanesulfonate (EMS) for 50min. Twenty-one reversion mutants were recovered, of
      which 17 were intragenic suppressors of the e665 mutation. The mutation frequency
      was 6.5-fold higher than when CB665 adults were similarly mutagenized, which was
      predicted given that cell-cycle checkpoints are muted in C. elegans embryos. The
      mutation spectrum was similar to that obtained after standard EMS mutagenesis. 

PMID- 25847272
TI  - Curcumin and trans-resveratrol exert cell cycle-dependent radioprotective or
      radiosensitizing effects as elucidated by the PCC and G2-assay.
AB  - Curcumin and trans-resveratrol are well-known antioxidant polyphenols with
      radiomodulatory properties, radioprotecting non-cancerous cells while
      radiosensitizing tumor cells. This dual action may be the result of their radical
      scavenging properties and their effects on cell-cycle checkpoints that are
      activated in response to radiation-induced chromosomal damage. It could be also
      caused by their effect on regulatory pathways with impact on detoxification
      enzymes, the up-regulation of endogenous protective systems, and cell-cycle
      dependent processes of DNA damage. This work aims to elucidate the mechanisms
      underlying the dual action of these polyphenols and investigates under which
      conditions they exhibit radioprotecting or radiosensitizing properties. The
      peripheral blood lymphocyte test system was used, applying concentrations ranging
      from 1.4 to 140MUM curcumin and 2.2 to 220MUM trans-resveratrol. The experimental
      design focuses first on their radioprotective effects in non-cycling lymphocytes,
      as uniquely visualized using cell fusion-mediated premature chromosome
      condensation, excluding, thus, cell-cycle interference to repair processes and
      activation of checkpoints. Second, the radiosensitizing potential of these
      chemicals on the induction of chromatid breaks in cultured lymphocytes following
      G2-phase irradiation was evaluated by a standardized G2-chromosomal
      radiosensitivity predictive assay. This assay uses caffeine for G2-checkpoint
      abrogation and it was applied to obtain an internal control for radiosensitivity
      testing, which simulates conditions similar to those of the highly radiosensitive
      lymphocytes of AT patients. The results demonstrate for the first time the cell
      cycle-dependent action of these polyphenols. When non-cycling cells are
      irradiated, the radioprotective properties of curcumin and trans-resveratrol are
      more prominent. However, when cycling cells are irradiated during G2-phase, the
      radiosensitizing features of these compounds are more pronounced. This
      observation offers a new biological basis for the mechanisms underlying the
      action of these polyphenols in cancer radiotherapy. 

PMID- 25847273
TI  - Direct observation of preferential processing of clustered abasic DNA damages
      with APE1 in TATA box and CpG island by reaction kinetics and fluorescence
      dynamics.
AB  - Sequences like the core element of TATA box and CpG island are frequently
      encountered in the genome and related to transcription. The fate of repair of
      clustered abasic sites in such sequences of genomic importance is largely
      unknown. This prompted us to investigate the sequence dependence of cleavage
      efficiency of APE1 enzyme at abasic sites within the core sequences of TATA box
      and CpG island using fluorescence dynamics and reaction kinetics. Simultaneous
      molecular dynamics study through steady state and time resolved fluorescence
      spectroscopy using unique ethidium bromide dye release assay confirmed an
      elevated amount of abasic site cleavage of the TATA box sequence as compared to
      the core CpG island. Reaction kinetics showed that catalytic efficiency of APE1
      for abasic site cleavage of core CpG island sequence was ~4 times lower as
      compared to that of the TATA box. Higher value of Km was obtained from the core
      CpG island sequence than the TATA box sequence. This suggests a greater binding
      effect of APE1 enzyme on TATA sequence that signifies a prominent role of the
      sequence context of the DNA substrate. Evidently, a faster response from APE1 was
      obtained for clustered abasic damage repair of TATA box core sequences than CpG
      island consensus sequences. The neighboring bases of the abasic sites in the
      complementary DNA strand were found to have significant contribution in addition
      to the flanking bases in modulating APE1 activity. The repair refractivity of the
      bistranded clustered abasic sites arise from the slow processing of the second
      abasic site, consequently resulting in decreased overall production of
      potentially lethal double strand breaks. 

PMID- 25847275
TI  - Peroxide promoted tunable decarboxylative alkylation of cinnamic acids to form
      alkenes or ketones under metal-free conditions.
AB  - A tunable decarboxylative alkylation of cinnamic acids with alkanes was developed
      to form alkenes or ketones under transition metal-free conditions. In the
      presence of DTBP or DTBP/TBHP, the reaction gave alkenes and ketones respectively
      via a radical mechanism in moderate to good yields. 

PMID- 25847274
TI  - Deletion of BRCA2 exon 27 causes defects in response to both stalled and
      collapsed replication forks.
AB  - BRCA2 is a tumor suppressor that maintains genomic integrity through double
      strand break (DSB) repair and replication fork protection. The BRC motifs and an
      exon 27-encoded domain (Ex27) of BRCA2 interact with the recombinase RAD51 to,
      respectively, facilitate the formation and stability of a RAD51 filament on
      single strand DNA. The BRC-RAD51 associations enable DSB repair while the Ex27
      RAD51 association protects the nascent replication strand from MRE11-mediated
      degradation. MRE11 is a nuclease that facilitates the generation of 3' overhangs
      needed for homologous recombination (HR)-mediated DSB repair. Here we report the
      dynamics of replication fork maintenance in mouse embryonic stem (ES) cells
      deleted for Ex27 (brca2(lex1/lex2)) after exposure to hydroxyurea (HU) that
      depletes nucleotides. HU conditions were varied from mild to severe. Mild
      conditions induce an ATR-response to replication fork stalling while severe
      conditions induce a DNA-PKCS-response to replication fork collapse and a DSB.
      These responses were differentiated by replication protein A (RPA)
      phosphorylation. We found that Ex27 deletion reduced MRE11 localization to
      stalled, but not collapsed, replication forks and that Ex27-deletion caused a
      proportionately more severe phenotype with HU dose. Therefore, the BRCA2 exon 27
      domain maintains chromosomal integrity at both stalled and collapsed replication
      forks consistent with involvement in both replication fork maintenance and double
      strand break repair. 

PMID- 25847276
TI  - Therapist competence in global mental health: Development of the ENhancing
      Assessment of Common Therapeutic factors (ENACT) rating scale.
AB  - Lack of reliable and valid measures of therapist competence is a barrier to
      dissemination and implementation of psychological treatments in global mental
      health. We developed the ENhancing Assessment of Common Therapeutic factors
      (ENACT) rating scale for training and supervision across settings varied by
      culture and access to mental health resources. We employed a four-step process in
      Nepal: (1) Item generation: We extracted 1081 items (grouped into 104 domains)
      from 56 existing tools; role-plays with Nepali therapists generated 11 additional
      domains. (2) Item relevance: From the 115 domains, Nepali therapists selected 49
      domains of therapeutic importance and high comprehensibility. (3) Item utility:
      We piloted the ENACT scale through rating role-play videotapes, patient session
      transcripts, and live observations of primary care workers in trainings for
      psychological treatments and the Mental Health Gap Action Programme (mhGAP). (4)
      Inter-rater reliability was acceptable for experts (intraclass correlation
      coefficient, ICC(2,7) = 0.88 (95% confidence interval (CI) 0.81-0.93), N = 7) and
      non-specialists (ICC(1,3) = 0.67 (95% CI 0.60-0.73), N = 34). In sum, the ENACT
      scale is an 18-item assessment for common factors in psychological treatments,
      including task-sharing initiatives with non-specialists across cultural settings.
      Further research is needed to evaluate applications for therapy quality and
      association with patient outcomes.

PMID- 25847277
TI  - Enhancement of the photoluminescence and long afterglow properties of
      Sr2MgSi2O7:Eu(2+) phosphor by Dy(3+) co-doping.
AB  - Sr2MgSi2O7:Eu(2+) and Sr2MgSi2O7:Eu(2+),Dy(3+) long afterglow phosphors were
      synthesized under a weak reducing atmosphere by the traditional high temperature
      solid state reaction method. The synthesized phosphors were characterized by
      powder X-ray diffraction (XRD), energy dispersive X-ray spectroscopy (EDX), and
      photo-, thermo- and mechanoluminescence spectroscopic techniques. The phase
      structure of the sintered phosphor was an akermanite type structure, which
      belongs to tetragonal crystallography. The thermoluminescence properties of these
      phosphors were investigated and compared. Under ultraviolet light excitation, the
      emission spectra of both prepared phosphors were composed of a broad emission
      band peaking at 470 nm. When the Sr2MgSi2O7:Eu(2+) phosphor was co-doped with
      Dy(3+), the photoluminescence (PL), afterglow and mechanoluminescence (ML)
      intensity were strongly enhanced. The decay graph indicated that both the
      sintered phosphors contained fast decay and slow decay processes. The ML
      intensities of Sr2MgSi2O7:Eu(2+) and Sr2MgSi2O7:Eu(2+),Dy(3+) phosphors were
      increased proportionally with increasing impact velocity, a finding that suggests
      that these phosphors could be used as sensors to detect the stress of an object.

PMID- 25847278
TI  - Self-synthesized extracellular matrix contributes to mature adipose tissue
      regeneration in a tissue engineering chamber.
AB  - The development of an engineered adipose tissue substitute capable of supporting
      reliable, predictable, and complete fat tissue regeneration would be of value in
      plastic and reconstructive surgery. For adipogenesis, a tissue engineering
      chamber provides an optimized microenvironment that is both efficacious and
      reproducible; however, for reasons that remain unclear, tissues regenerated in a
      tissue engineering chamber consist mostly of connective rather than adipose
      tissue. Here, we describe a chamber-based system for improving the yield of
      mature adipose tissue and discuss the potential mechanism of adipogenesis in
      tissue-chamber models. Adipose tissue flaps with independent vascular pedicles
      placed in chambers were implanted into rabbits. Adipose volume increased
      significantly during the observation period (week 1, 2, 3, 4, 16).
      Histomorphometry revealed mature adipose tissue with signs of adipose tissue
      remolding. The induced engineered constructs showed high-level expression of
      adipogenic (peroxisome proliferator-activated receptor gamma), chemotactic
      (stromal cell-derived factor 1a), and inflammatory (interleukin 1 and 6) genes.
      In our system, the extracellular matrix may have served as a scaffold for cell
      migration and proliferation, allowing mature adipose tissue to be obtained in a
      chamber microenvironment without the need for an exogenous scaffold. Our results
      provide new insights into key elements involved in the early development of
      adipose tissue regeneration. 

PMID- 25847279
TI  - Fractal and stochastic geometry inference for breast cancer: a case study with
      random fractal models and Quermass-interaction process.
AB  - Fractals are models of natural processes with many applications in medicine. The
      recent studies in medicine show that fractals can be applied for cancer detection
      and the description of pathological architecture of tumors. This fact is not
      surprising, as due to the irregular structure, cancerous cells can be interpreted
      as fractals. Inspired by Sierpinski carpet, we introduce a flexible parametric
      model of random carpets. Randomization is introduced by usage of binomial random
      variables. We provide an algorithm for estimation of parameters of the model and
      illustrate theoretical and practical issues in generation of Sierpinski gaskets
      and Hausdorff measure calculations. Stochastic geometry models can also serve as
      models for binary cancer images. Recently, a Boolean model was applied on the 200
      images of mammary cancer tissue and 200 images of mastopathic tissue. Here, we
      describe the Quermass-interaction process, which can handle much more variations
      in the cancer data, and we apply it to the images. It was found out that
      mastopathic tissue deviates significantly stronger from Quermass-interaction
      process, which describes interactions among particles, than mammary cancer tissue
      does. The Quermass-interaction process serves as a model describing the tissue,
      which structure is broken to a certain level. However, random fractal model fits
      well for mastopathic tissue. We provide a novel discrimination method between
      mastopathic and mammary cancer tissue on the basis of complex wavelet-based self
      similarity measure with classification rates more than 80%. Such similarity
      measure relates to Hurst exponent and fractional Brownian motions. The R package
      FractalParameterEstimation is developed and introduced in the paper.

PMID- 25847280
TI  - Mildronate (Meldonium) in professional sports - monitoring doping control urine
      samples using hydrophilic interaction liquid chromatography - high
      resolution/high accuracy mass spectrometry.
AB  - To date, substances such as Mildronate (Meldonium) are not on the radar of anti
      doping laboratories as the compound is not explicitly classified as prohibited.
      However, the anti-ischemic drug Mildronate demonstrates an increase in endurance
      performance of athletes, improved rehabilitation after exercise, protection
      against stress, and enhanced activations of central nervous system (CNS)
      functions. In the present study, the existing evidence of Mildronate's usage in
      sport, which is arguably not (exclusively) based on medicinal reasons, is
      corroborated by unequivocal analytical data allowing the estimation of the
      prevalence and extent of misuse in professional sports. Such data are vital to
      support decision-making processes, particularly regarding the ban on drugs in
      sport. Due to the growing body of evidence (black market products and athlete
      statements) concerning its misuse in sport, adequate test methods for the
      reliable identification of Mildronate are required, especially since the
      substance has been added to the 2015 World Anti-Doping Agency (WADA) monitoring
      program. In the present study, two approaches were established using an in-house
      synthesized labelled internal standard (Mildronate-D3 ). One aimed at the
      implementation of the analyte into routine doping control screening methods to
      enable its monitoring at the lowest possible additional workload for the
      laboratory, and another that is appropriate for the peculiar specifics of the
      analyte, allowing the unequivocal confirmation of findings using hydrophilic
      interaction liquid chromatography-high resolution/high accuracy mass spectrometry
      (HILIC-HRMS). Here, according to applicable regulations in sports drug testing, a
      full qualitative validation was conducted. The assay demonstrated good
      specificity, robustness (rRT=0.3%), precision (intra-day: 7.0-8.4%; inter-day:
      9.9-12.9%), excellent linearity (R>0.99) and an adequate lower limit of detection
      (<10 ng/mL).

PMID- 25847281
TI  - Oxygen uptake kinetics and exercise capacity in children with cystic fibrosis.
AB  - Exercise capacity, an objective measure of exercise intolerance, is known to
      predict quality of life and mortality in cystic fibrosis (CF). The mechanisms for
      exercise intolerance in patients with cystic fibrosis (CF), however, have yet to
      be fully elucidated. Accordingly, this study sought to investigate oxygen uptake
      kinetics and the impact of fat-free mass (FFM) on exercise capacity in young
      patients with CF. 16 young patients with CF (age 13 +/- 4 years; 10 female) and
      15 matched controls (age 14 +/- 3 years; nine female) participated. Pulmonary
      function and a maximal exercise test on a cycle ergometer using the Godfrey
      protocol were performed. Exercise capacity (VO2 peak), VO2 response time (VO2
      RT), and functional VO2 gain (DeltaVO2 /DeltaWR) were all determined. Lung
      function was the only demographic parameter significantly lower (P < 0.05) in CF
      compared to controls. Exercise capacity was lower in CF (P < 0.014) only when VO2
      peak was normalized for FFM (43.5 +/- 7.7 vs. 50.6 +/- 7.4 ml/kg-FFM/min) or
      expressed as % predicted (70.1 +/- 14.3 vs. 85.4 +/- 16.0%). The VO2 RT was
      slower (36.1 +/- 15.1 vs. 25.0 +/- 12.4 sec; P = 0.03) and the DeltaVO2 /DeltaWR
      slope was lower (8.4 +/- 3 ml/min/watt vs. 10.1 +/- 1.4 ml/min/watt; P = 0.02) in
      patients compared to controls, respectively. In conclusion, a delayed VO2
      response time coupled with the lower functional VO2 gain (DeltaVO2 /DeltaWR)
      suggest that young patients with CF have impairment in oxygen transport and
      oxygen utilization by the muscles. These data in addition to differences in VO2
      peak normalized for FFM provide some insight that muscle mass and muscle
      metabolism contribute to exercise intolerance in CF.

PMID- 25847283
TI  - Characterization of the effects of three Lactobacillus species on the function of
      chicken macrophages.
AB  - Lactobacillus acidophilus, Lactobacillus reuteri and Lactobacillus salivarius can
      influence the adaptive immune responses in chickens but vary in their ability to
      do so. The present study attempted to identify how these three bacteria alter the
      innate immune system. A chicken macrophage cell line, MQ-NCSU, was co-cultured
      with the three live Lactobacillus species, alone or in combination, grown at
      different temperatures for various durations of time. Late exponential growth
      phase bacteria were more immunostimulatory, while bacterial growth temperature
      had little effect. L. acidophilus and L. salivarius significantly increased
      nitric oxide (NO) production and phagocytosis, while L. reuteri did not. In fact,
      L reuteri was shown to inhibit NO production of macrophages when co-cultured with
      the other bacteria or when cells were pre-treated with LPS. The results
      demonstrate a possible molecular mechanism for the immunomodulatory effects of L.
      acidophilus and L. salivarius, and a unique immunomodulatory ability of L.
      reuteri. 

PMID- 25847284
TI  - Papillary meningioma in the dog: A clinicopathological case series study.
AB  - Papillary meningioma (PM) is one of the most aggressive variants of meningioma in
      humans and classified as grade III by WHO system. To date, the biological
      behavior of PM is still not clear in dogs. This study investigated the
      correlation between histopathological findings of 16 canine PMs and follow up
      data. Moreover, the expression of doublecortin, E-cadherin, and N-cadherin was
      investigated by immunohistochemistry. The supratentorial compartment resulted the
      most common involved. Despite the low grade of histological malignancy, 87.5% of
      dogs that underwent surgery experienced tumor recurrence. Intratumoral necrosis
      was observed in a strict correlation with malignancy histological parameter and
      tumor recurrence. The post-surgery mean survival time was much lower than thus
      observed in the most common histological subtypes. This data were also confirmed
      in dogs that received a conservative treatment alone. Tumors with a severe
      clinical behavior showed a high N-cadherin expression versus a low or absent E
      cadherin expression. 

PMID- 25847282
TI  - Pig-to-baboon heterotopic heart transplantation--exploratory preliminary
      experience with pigs transgenic for human thrombomodulin and comparison of three
      costimulation blockade-based regimens.
AB  - BACKGROUND: Three costimulation blockade-based regimens have been explored after
      transplantation of hearts from pigs of varying genetic backgrounds to determine
      whether CTLA4-Ig (abatacept) or anti-CD40mAb+CTLA4-Ig (belatacept) can
      successfully replace anti-CD154mAb. METHODS: All pigs were on an alpha1,3
      galactosyltransferase gene-knockout/CD46 transgenic (GTKO.CD46) background.
      Hearts transplanted into Group A baboons (n=4) expressed additional CD55, and
      those into Group B (n=3) expressed human thrombomodulin (TBM). Immunosuppression
      included anti-thymocyte globulin with anti-CD154mAb (Regimen 1: n=2) or abatacept
      (Regimen 2: n=2) or anti-CD40mAb+belatacept (Regimen 3: n=2). Regimens 1 and 2
      included induction anti-CD20mAb and continuous heparin. One further baboon in
      Group B (B16311) received a modified Regimen 1. Baboons were followed by
      clinical/laboratory monitoring of immune/coagulation parameters. At biopsy, graft
      failure, or euthanasia, the graft was examined by microscopy. RESULTS: Group A
      baboons survived 15 to 33 days, whereas Group B survived 52, 99, and 130 days,
      respectively. Thrombocytopenia and reduction in fibrinogen occurred within 21
      days in Group A, suggesting thrombotic microangiopathy (TM), confirmed by
      histopathology. In Group B, with follow-up for >4 m, areas of myofiber
      degeneration and scarring were seen in two hearts at necropsy. A T-cell response
      was documented only in baboons receiving Regimen 2. CONCLUSIONS: The combination
      of anti-CD40mAb+belatacept proved effective in preventing a T-cell response. The
      expression of TBM prevented thrombocytopenia and may possibly delay the
      development of TM and/or consumptive coagulopathy.

PMID- 25847285
TI  - The impact of vehicle motion during transport on animal welfare.
AB  - Motion sickness is a common response in humans and some species of farm livestock
      during transport, but research on the impact of motion has been primarily focused
      on the use of animal models for humans. During livestock transportation, animals
      seek to minimise uncontrolled movements to reduce energy consumption and maintain
      posture. Road and sea transport of livestock can produce motion sickness and
      stress responses. Clinical signs are the result of autonomous nervous system
      activation. Studies conducted on road transportation effects in domestic animals
      showed several motion sickness behaviours including vomiting and, in ruminants, a
      reduction in rumination. However, there is a lack of knowledge on the impact of
      sea transport motion. Despite the paucity of data on livestock, there is
      sufficient evidence to believe that motion might affect animal welfare when
      animals are transported by road or sea. 

PMID- 25847286
TI  - Trp(250) -hK2 is defective in intracellular trafficking and activates the
      unfolded protein response.
AB  - hK2, a member of the kallikrein protease family encoded by KLK2, is expressed
      exclusively in prostate and is a putative adjunct tumor marker for prostate
      cancer screening. The T allele of rs198977, a single nucleotide polymorphism in
      exon 5 of KLK2, codes for W-hK2 and is associated with lower serum hK2 levels and
      higher risk of prostate cancer than the C allele encoding R-hK2. To elucidate the
      mechanism that underlies this SNP's function, we transfected plasmids expressing
      R-hK2 or W-hK2 into PC3, HeLa and HEK293A cells and measured the hK2 level in
      cell lysates and conditioned media. The level of W-hK2 was lower than R-hK2 in
      conditioned media but was not different from R-hK2 in cell lysates. W-hK2 was
      hardly colocalized with Golgi-targeted fluorescent protein whereas R-hK2
      colocalized. Reporter assays related to the unfolded protein response (UPR) and
      phospho-eIF2alpha immunoblot showed that W-hK2 increased UPR activity more than R
      hK2. These results indicated that W-hK2 had a defect in cellular trafficking from
      the ER to the Golgi complex due to its misfolding and that it activated the UPR,
      suggesting a mechanism to explain the association of the T allele with higher
      prostate cancer risk. 

PMID- 25847287
TI  - Dual Trajectories of Cigarette Smoking and Smokeless Tobacco Use From Adolescence
      to Midlife Among Males in a Midwestern US Community Sample.
AB  - INTRODUCTION: Identifying trajectories of tobacco use is critical for
      understanding its natural history and targeting interventions, but research on
      trajectories of smokeless tobacco and dual use of smokeless tobacco and
      cigarettes is very limited. This study identified tobacco use trajectories from
      adolescence to midlife and tested correlates of trajectory group membership.
      METHODS: This study included all male participants in a longitudinal study who
      reported cigarette smoking or smokeless tobacco use in 1987, 1993, 1999, 2005, or
      2011 (N = 2230). Group-based trajectory analyses were conducted with zero
      inflated Poisson models. Analysis of covariance was used to test adolescent
      health beliefs associated with trajectory group membership. RESULTS: Five smoking
      trajectory groups were identified: (1) consistent abstinence from cigarettes; (2)
      late onset intermittent, then cessation; (3) early onset regular, then cessation;
      (4) delayed onset regular, then cessation; and (5) consistent regular. Four
      smokeless tobacco trajectory groups were identified: (1) early onset, then
      cessation; (2) consistent abstinence from smokeless tobacco; (3) late onset,
      escalating; and (4) consistent regular. The proportion of participants in
      trajectory groups representing dual use was low. Adolescent beliefs favorable to
      smoking and smokeless tobacco were associated with membership in consistent
      regular use groups. CONCLUSIONS: The prevalence of dual use of cigarettes and
      smokeless tobacco was low, and there was little evidence to suggest switching
      between tobacco products. Participants who held more positive beliefs about
      smoking and smokeless tobacco as adolescents were more likely to be consistent
      regular users of cigarettes and smokeless tobacco into adulthood.

PMID- 25847288
TI  - The Association of Panic Disorder, Posttraumatic Stress Disorder, and Major
      Depression With Smoking in American Indians.
AB  - INTRODUCTION: Rates of cigarette smoking are disproportionately high among
      American Indian populations, although regional differences exist in smoking
      prevalence. Previous research has noted that anxiety and depression are
      associated with higher rates of cigarette use. We asked whether lifetime panic
      disorder, posttraumatic stress disorder, and major depression were related to
      lifetime cigarette smoking in two geographically distinct American Indian tribes.
      METHODS: Data were collected in 1997-1999 from 1506 Northern Plains and 1268
      Southwest tribal members; data were analyzed in 2009. Regression analyses
      examined the association between lifetime anxiety and depressive disorders and
      odds of lifetime smoking status after controlling for sociodemographic variables
      and alcohol use disorders. Institutional and tribal approvals were obtained for
      all study procedures, and all participants provided informed consent. RESULTS:
      Odds of smoking were two times higher in Southwest participants with panic
      disorder and major depression, and 1.7 times higher in those with posttraumatic
      stress disorder, after controlling for sociodemographic variables. After
      accounting for alcohol use disorders, only major depression remained
      significantly associated with smoking. In the Northern Plains, psychiatric
      disorders were not associated with smoking. Increasing psychiatric comorbidity
      was significantly linked to increased smoking odds in both tribes, especially in
      the Southwest. CONCLUSIONS: This study is the first to examine the association
      between psychiatric conditions and lifetime smoking in two large, geographically
      diverse community samples of American Indians. While the direction of the
      relationship between nicotine use and psychiatric disorders cannot be determined,
      understanding unique social, environmental, and cultural differences that
      contribute to the tobacco-psychiatric disorder relationship may help guide tribe
      specific commercial tobacco control strategies.

PMID- 25847289
TI  - Combinations of CYP2A6*4 and Glutathione S-Transferases Gene Polymorphisms Modify
      the Association Between Maternal Secondhand Smoke Exposure During Pregnancy and
      Small-for-Gestational-Age.
AB  - INTRODUCTION: Risk of small-for-gestational-age (SGA) birth varied considerably
      in women exposed to secondhand smoke (SHS) during pregnancy. We examined whether
      this variation was explained by mothers' one Phase I (CYP2A6*4, activation of
      tobacco toxics) and two Phase II (GSTM1 and GSTT1, detoxification) metabolic
      genotypes. METHODS: We enrolled 468 Chinese pregnant women (115 delivering SGA
      and 353 delivering non-SGA newborns) shortly before delivery. SHS exposure during
      pregnancy was defined as self-reported daily exposure time being more than 0
      minute. We fitted multivariable logistic regression models to examine whether
      CYP2A6*4, GSTM1, and GSTT1 gene polymorphsims and their combinations modified the
      association between SHS exposure and SGA. RESULTS: In the total sample, more
      mothers of SGA newborns were exposed to SHS during pregnancy than mothers of non
      SGA newborns (38.3% vs. 31.4%). CYP2A6*4, GSTM1, and GSTT1 genes alone could not
      modify the association between SHS exposure and SGA. The combination of CYP2A6*4
      and GSTT1 high-risk genotypes (CYP2A6*1/*1 and GSTT1-absent [high-risk] vs. other
      combinations as a whole [low-risk]) significantly (P value, .045) modified the
      association between SHS exposure and SGA. Among mothers with high-risk genotypes,
      SHS during pregnancy was significantly associated with SGA (confounder-adjusted
      odds ratio, 2.31 [95% confidence interval, 1.20-4.42]). Among mothers with low
      risk genotypes, however, SHS exposure during pregnancy was not associated with
      SGA (1.14 [0.64-2.04]). CONCLUSIONS: Chinese pregnant women with the combination
      of CYP2A6*1/*1 and GSTT1-absent genotypes are at particularly high-risk of SHS
      related SGA.

PMID- 25847290
TI  - Smoking Status Confirmation by Proxy: Validation in a Smoking Cessation Trial.
AB  - INTRODUCTION: Biochemical confirmation (BC) of self-report is the gold standard
      of evidence for abstinence in smoking cessation research, but difficulty in
      obtaining samples may bias estimates of quit rates. Proxy confirmation (PC) has
      not been validated in cessation trials. We assessed the feasibility and validity
      of PC in a cessation trial for hospitalized smokers. METHODS: We enrolled 402
      daily cigarette smokers during a hospital admission. At enrollment, participants
      provided demographics, smoking history, and named proxies to confirm their
      smoking status at follow-up. Participants provided self-reported (SR) 7-day
      tobacco abstinence by telephone at 6 months post-discharge. SR quitters were
      asked to mail a saliva sample for BC. Incentives were offered for survey
      completion ($20) and returned samples ($50). We called proxies for all those with
      SR to obtain PC. Quit rates were calculated with missing data indicating smoking.
      We assessed associations of nonresponse with baseline characteristics using chi
      squared tests and logistic regression. We calculated the sensitivity and
      specificity of PC in detecting smokers as determined by BC. RESULTS: All patients
      named at least one proxy. Response rates were 82% for SR, 84% for PC, and 69% for
      BC. Observed participant characteristics were unrelated to provision of sample
      for BC. Estimated quit rates were 35% for SR, 27% for SR + PC, 21% for SR + BC
      and 27% for SR + BC or PC. Sensitivity of PC was not higher than SR (73% vs.
      77%); specificity was lower (84% vs. 100%). CONCLUSION: PC was feasible but not
      superior to self-report in a cessation trial.

PMID- 25847291
TI  - Smoke-Free School Policy and Exposure to Secondhand Smoke: A Quasi-Experimental
      Analysis.
AB  - INTRODUCTION: Tobacco control prevention efforts are important to protect people
      from exposure to dangerous tobacco smoke, support cessation, and reduce tobacco
      use initiation. While smoke-free laws have been a widespread tobacco control
      strategy, little work has been done to examine the impact of smoke-free school
      policies. The objective of this study is to evaluate the impact of provincial
      smoke-free school ground policies on youth-reported exposure to secondhand smoke
      (SHS) on school property. METHODS: This study used a nationally representative
      sample of 20 388 youth aged 15-18 from the 2005-2012 Canadian Tobacco Use
      Monitoring Survey. A quasi-experimental design was used to evaluate the impact of
      smoke-free school policies on SHS exposure. RESULTS: Approximately over half
      (52%) of respondents reported SHS exposure on a school property in the past
      month. Smoke-free school policy had a statistically significant effect on SHS
      exposure. Specifically, the adoption of smoke-free school reduced the probability
      of SHS exposure by about 8 percentage points. Respondents who were smokers were
      more likely to report being exposed to SHS than nonsmokers. Likewise, those
      living in urban areas had higher probability of being exposed to SHS than those
      living in rural parts of Canada. CONCLUSIONS: Reported exposure to tobacco smoke
      did decrease after the introduction of smoke-free ground policies; however,
      almost half of high-school aged youth report exposure in the last month. Across
      Canada, provincial health authorities as well as school administers may need to
      assess the implementation of these smoke-free policies and improve enforcement
      strategies to further reduce exposure to dangerous SHS.

PMID- 25847293
TI  - Relapse-Prevention Booklets as an Adjunct to a Tobacco Quitline: A Randomized
      Controlled Effectiveness Trial.
AB  - INTRODUCTION: Relapse prevention (RP) remains a major challenge to smoking
      cessation. Previous research found that a set of self-help RP booklets
      significantly reduced smoking relapse. This study tested the effectiveness of RP
      booklets when added to the existing services of a telephone quitline. METHODS:
      Quitline callers (N = 3458) were enrolled after their 2-week quitline follow-up
      call and randomized to one of three interventions: (1) Usual Care: standard
      intervention provided by the quitline, including brief counseling and nicotine
      replacement therapy; (2) Repeated Mailings (RM): eight Forever Free RP booklets
      sent to participants over 12 months; and (3) Massed Mailings: all eight Forever
      Free RP booklets sent upon enrollment. Follow-ups were conducted at 6-month
      intervals, through 24 months. The primary outcome measure was 7-day-point
      prevalence-abstinence. RESULTS: Overall abstinence rates were 61.0% at baseline,
      and 41.9%, 42.7%, 44.0%, and 45.9% at the 6-, 12-, 18- and 24-month follow-ups,
      respectively. Although RM produced higher abstinence rates, the differences did
      not reach significance for the full sample. Post-hoc analyses of at-risk
      subgroups revealed that among participants with high nicotine dependence (n =
      1593), the addition of RM materials increased the abstinence rate at 12 months
      (42.2% vs. 35.2%; OR = 1.38; 95% CI = 1.03% to 1.85%; P = .031) and 24 months
      (45% vs. 38.8%; OR = 1.31; 95% CI = 1.01% to 1.73%; P = .046). CONCLUSIONS:
      Sending self-help RP materials to all quitline callers appears to provide little
      benefit to deterring relapse. However, selectively sending RP booklets to callers
      explicitly seeking assistance for RP and those identified as highly dependent on
      nicotine might still prove to be worthwhile.

PMID- 25847294
TI  - Corneal hypoesthesia with normal sub-basal nerve density following surgery for
      trigeminal neuralgia.
AB  - PURPOSE: To evaluate the corneal sub-basal nerve plexus in patients presenting
      with hypoesthesia following surgery for trigeminal neuralgia. METHODS: Twenty-one
      patients who had unilateral medically uncontrolled trigeminal neuralgia and
      underwent ipsilateral surgery from 2006 to 2012 were included. Of these, 10 had
      microvascular decompression (MVD group) and 11 had balloon compression of the
      trigeminal ganglion (BC group). Slit lamp examination, Cochet-Bonnet
      aesthesiometery and in vivo confocal microscopy were carried out on both eyes of
      each patient. Nerve density data were statistically analysed. RESULTS: Corneal
      sensations and sub-basal nerve densities in MVD group were normal and equal in
      both the operated and unoperated sides, indicating that there was no intra
      operative damage of the ophthalmic division of the trigeminal nerve (V1).
      However, those in BC group, despite having significantly reduced corneal
      sensations on the operated side (p = 0.007), did not demonstrate any significant
      difference in their sub-basal nerve densities (p = 0.477). No patient had any
      ocular symptoms. CONCLUSIONS: This study supports the hypothesis that complete
      ganglionic damage and/or postganglionic damage of V1 results in corneal
      hypoesthesia and neurotrophic keratitis, but partial ganglionic or preganglionic
      damage would preserve trophic function despite hypoesthesia and not result in
      clinically significant symptoms or signs of neurotrophic keratitis. The trophic
      and sensory functions of V1 are therefore independent and can be dissociated by
      disease or injury.

PMID- 25847295
TI  - Nonylphenol diethoxylate inhibits apoptosis induced in PC12 cells.
AB  - Nonylphenol and short-chain nonylphenol ethoxylates such as NP2 EO are present in
      aquatic environment as wastewater contaminants, and their toxic effects on
      aquatic species have been reported. Apoptosis has been shown to be induced by
      serum deprivation or copper treatment. To understand the toxicity of nonylphenol
      diethoxylate, we investigated the effects of NP2 EO on apoptosis induced by serum
      deprivation and copper by using PC12 cell system. Nonylphenol diethoxylate itself
      showed no toxicity and recovered cell viability from apoptosis. In addition,
      nonylphenol diethoxylate decreased DNA fragmentation caused by apoptosis in PC12
      cells. This phenomenon was confirmed after treating apoptotic PC12 cells with
      nonylphenol diethoxylate, whereas the cytochrome c release into the cytosol
      decreased as compared to that in apoptotic cells not treated with nonylphenol
      diethoxylates. Furthermore, Bax contents in apoptotic cells were reduced after
      exposure to nonylphenol diethoxylate. Thus, nonylphenol diethoxylate has the
      opposite effect on apoptosis in PC12 cells compared to nonylphenol, which
      enhances apoptosis induced by serum deprivation. The difference in structure of
      the two compounds is hypothesized to be responsible for this phenomenon. These
      results indicated that nonylphenol diethoxylate has capability to affect cell
      differentiation and development and has potentially harmful effect on organisms
      because of its unexpected impact on apoptosis. (c) 2015 Wiley Periodicals, Inc.
      Environ Toxicol 31: 1389-1398, 2016.

PMID- 25847296
TI  - Cancer-related fatigue: a survey of health practitioner knowledge and practice.
AB  - PURPOSE: This study aims to identify the current practices of health
      professionals in the assessment and treatment of cancer-related fatigue (CRF).
      METHODS: Health professionals working with oncology clients participated in an
      electronic survey distributed via professional associations and oncology
      societies. RESULTS: One hundred twenty-nine professionals from nursing, medical,
      and allied health disciplines participated in an electronic survey. Overall,
      there was a perception that CRF was inadequately managed at some facilities.
      Routine fatigue screening processes in the workplace were reported by more than
      half of participants; however, less than one quarter used a clinical guideline or
      conducted in-depth CRF assessments. Awareness of interventions for CRF varied
      amongst participants with one quarter able to list five appropriate interventions
      for cancer-related fatigue. Access to services for managing fatigue was
      inconsistent across service types, with post-treatment triage a high priority for
      CRF in some organisations yet not others. Participants identified a need for
      improved guidelines, enhanced expertise and better access to services for people
      with CRF. CONCLUSIONS: There is a need for further education in CRF management
      for a range of health disciplines in oncology and additional resources to
      facilitate translation of CRF guidelines into clinical practice.

PMID- 25847292
TI  - Interaction of Cigarette Smoking History With APOE Genotype and Age on Amyloid
      Level, Glucose Metabolism, and Neurocognition in Cognitively Normal Elders.
AB  - INTRODUCTION: Chronic cigarette smoking is associated with increased risk for
      Alzheimer's disease (AD). The goal of this study was to determine if smoking
      history moderated the associations of age and APOE genotype (the most robust risk
      factors for AD) on brain amyloid deposition, glucose metabolism, and
      neurocognition in cognitively-normal elders. METHODS: Participants (n = 264) were
      grouped according to their APOE epsilon4 carrier status (epsilon4 carrier:
      APOE4+; non-epsilon4 carrier: APOE4-) and smoking status (smokers: at least 1
      year of smoking during lifetime; never-smokers: no history of smoking).
      Approximately 89% of the smoking sample was former-smokers. We specifically
      tested for interactions of smoking status with APOE epsilon4 carrier status and
      age on measures of cortical amyloid deposition, glucose metabolism, and
      neurocognition. RESULTS: (1) smoking status interacted with APOE epsilon4 carrier
      status, where smoker APOE4+ showed lower glucose metabolism and poorer auditory
      verbal learning and memory than never-smoking APOE4-, never-smoking APOE4+, and
      smoking APOE4-; (2) smoking status interacted with age on measures of semantic
      fluency, processing speed/set-shifting and global neurocognition; smokers,
      irrespective of APOE epsilon4 carrier status, demonstrated poorer performance
      with increasing age than never-smokers; and (3) smoking APOE4+ and never-smoking
      APOE4+ showed greater cortical amyloid deposition than never-smoking APOE4- and
      smoking APOE4-. CONCLUSIONS: The findings indicate consideration of smoking
      history is essential to both better understand the factors associated with
      neurobiological and neurocognitive abnormalities in elders, and the risk for
      development of AD-related neuropathology.

PMID- 25847298
TI  - The combination of milatuzumab, a humanized anti-CD74 antibody, and veltuzumab, a
      humanized anti-CD20 antibody, demonstrates activity in patients with relapsed and
      refractory B-cell non-Hodgkin lymphoma.
AB  - As a result of the anti-tumour activity observed in vitro and in vivo with
      combined anti-CD20 and anti-CD74 antibodies, we initiated a phase I/II trial of
      veltuzumab and milatuzumab in patients with relapsed or refractory B-cell non
      Hodgkin lymphoma (NHL). Patients received an induction of veltuzumab 200 mg/m(2)
      weekly combined with escalating doses of milatuzumab at 8, 16 and 20 mg/kg weekly
      for 4 weeks. Patients without disease progression could receive an extended
      induction with treatment on weeks 12, 20, 28 and 36. A total of 35 patients
      enrolled on the study. Median age was 63 years, median number of prior therapies
      was 3, and 63% of patients were rituximab refractory. No dose-limiting toxicities
      were observed in the phase I study. Related grade 3-4 toxicities included
      lymphopenia, leucopenia, neutropenia, anaemia, infusion reactions,
      hyperglycaemia, fatigue and atrial tachycardia. Median weeks of therapy was 12
      and 29% of patients completed all 36 weeks of therapy. The overall response rate
      was 24%, median duration of response was 12 months, and responses were observed
      at all dose levels and in 50% of patients refractory to rituximab. Combination
      therapy with veltuzumab and milatuzumab demonstrated activity in a population of
      heavily pre-treated patients with relapsed or refractory indolent NHL. 

PMID- 25847297
TI  - The HIV proteins Tat and Nef promote human bone marrow mesenchymal stem cell
      senescence and alter osteoblastic differentiation.
AB  - To maintain bone mass turnover and bone mineral density (BMD), bone marrow (BM)
      mesenchymal stem cells (MSCs) are constantly recruited and subsequently
      differentiated into osteoblasts. HIV-infected patients present lower BMD than non
      HIV infected individuals and a higher prevalence of osteopenia/osteoporosis. In
      antiretroviral treatment (ART)-naive patients, encoded HIV proteins represent
      pathogenic candidates. They are released by infected cells within BM and can
      impact on neighbouring cells. In this study, we tested whether HIV proteins Tat
      and/or Nef could induce senescence of human BM-MSCs and reduce their capacity to
      differentiate into osteoblasts. When compared to nontreated cells, MSCs
      chronically treated with Tat and/or Nef up to 30 days reduced their proliferative
      activity and underwent early senescence, associated with increased oxidative
      stress and mitochondrial dysfunction. The antioxidant molecule N-acetyl- cysteine
      had no or minimal effects on Tat- or Nef-induced senescence. Tat but not Nef
      induced an early increase in NF-kappaB activity and cytokine/chemokine secretion.
      Tat-induced effects were prevented by the NF-kappaB inhibitor parthenolide,
      indicating that Tat triggered senescence via NF-kappaB activation leading to
      oxidative stress. Otherwise, Nef- but not Tat-treated cells displayed early
      inhibition of autophagy. Rapamycin, an autophagy inducer, reversed Nef-induced
      senescence and oxidative stress. Moreover, Tat+Nef had cumulative effects.
      Finally, Tat and/or Nef decreased the MSC potential of osteoblastic
      differentiation. In conclusion, our in vitro data show that Tat and Nef could
      reduce the number of available precursors by inducing MSC senescence, through
      either enhanced inflammation or reduced autophagy. These results offer new
      insights into the pathophysiological mechanisms of decreased BMD in HIV-infected
      patients.

PMID- 25847299
TI  - Retargeting of bile salt export pump and favorable outcome in children with
      progressive familial intrahepatic cholestasis type 2.
AB  - We investigated predictors of clinical evolution in progressive familial
      intrahepatic cholestasis type 2 patients and how they relate to bile salt export
      pump (BSEP) expression and its (re)targeting. Our retrospective study included 22
      children with progressive familial intrahepatic cholestasis type 2. Clinical,
      biochemical, and histological characteristics were reviewed on admittance and
      following treatment with either ursodeoxycholic acid alone (10 mg/kg thrice
      daily, n = 19) or partial biliary diversion (n = 3). Immunostaining of BSEP was
      performed in 20 patients. Response to treatment was defined as normalization of
      pruritus, disappearance of jaundice, and alanine aminotransferase (ALT) levels
      <1.5 times the upper limit of normal. Ten of 22 patients were responders, and
      paired biopsies were available in six. De novo or retargeted canalicular
      expression of BSEP occurred in four of these six, two of whom exhibited baseline
      intracellular expression. Twelve of 22 were nonresponders and exhibited earlier
      onset of jaundice (<9 months), neonatal cholestasis, and higher ALT levels. An
      ALT >165 IU/L produced 72% sensitivity and 55% specificity in predicting
      nonresponse. Seven patients were still responding at last follow-up (median = 20
      months, range 5-67 months). Three responders relapsed after 56, 72, and 82
      months, respectively. Of nine surviving responders, median relapse-free survival
      time was 72 months (95% confidence interval 48-96 months) and 5-year relapse-free
      survival was 75% (95% confidence interval 33-100%). Intracellular BSEP at
      baseline was seen in six, of whom five were responders. Genetic analysis was
      performed in 17 of 22, confirming diagnosis in 13 (76%) and in four (24%) in whom
      only heterozygous mutation was identified. CONCLUSION: De novo or retargeted
      canalicular expression of BSEP occurs in treatment responders; children with late
      onset presentation, lower ALT, and intracellular BSEP expression are likely to
      respond, at least transiently, to nontransplant treatment.

PMID- 25847300
TI  - A tale of two macrophages: to Shb or not to Shb.

PMID- 25847301
TI  - Modulation of pre-attentive spectro-temporal feature processing in the human
      auditory system by HD-tDCS.
AB  - The present study examined the functional lateralization of the human auditory
      cortex (AC) for pre-attentive spectro-temporal feature processing. By using high
      definition transcranial direct current stimulation (HD-tDCS), we systematically
      modulated neuronal activity of the bilateral AC. We assessed the influence of
      anodal and cathodal HD-tDCS delivered over the left or right AC on auditory
      mismatch negativity (MMN) in response to temporal as well as spectral deviants in
      12 healthy subjects. The results showed that MMN to temporal deviants was
      significantly enhanced by anodal HD-tDCS applied over the left AC only. Our data
      indicate a left hemispheric dominance for the pre-attentive processing of low
      level temporal information. 

PMID- 25847302
TI  - A forward to optimization of antivenom therapy: An in vivo study upon the
      effectiveness of the antivenom against early and delayed nephrotoxicity induced
      by the venom of the Iranian scorpion Hemiscorpius lepturus in rat.
AB  - The aim of the present in vivo study was to identify the optimal effective dose,
      the most favorable time and the route of administration of the available
      polyvalent scorpion antivenom against the toxic effects induced by Hemiscorpius
      lepturus (H. lepturus) venom in rat. The end point for assessment included
      measurement of alanin-amino-peptidase (AAP) and N-acetyl-b-d-glucosaminidase
      (NAG), biochemical urine analysis and histopathological assessment. The results
      showed that a single subcutaneous 50 MUg of the venom produced significant
      increase in the AAP and NAG enzyme activity, urinary biochemical parameters and
      induced histopathological structural abnormalities in the renal system. The
      optimal effective co-administered dose of the antivenom was 0.5 ml, which when
      administered 1 and 2 h of envenomation by intravenous (IV) and subcutaneous (SC)
      routes respectively produced significant protection against these toxic effects.
      Prudently, the significance of these findings need to be assessed in further
      clinical studies. 

PMID- 25847304
TI  - Stroke awareness and knowledge in an urban New Zealand population.
AB  - BACKGROUND: Stroke is the third most common cause of death and a major cause of
      chronic disability in New Zealand. Linked to risk factors that develop across the
      life-course, stroke is considered to be largely preventable. This study assessed
      the awareness of stroke risk, symptoms, detection, and prevention behaviors in an
      urban New Zealand population. METHODS: Demographics, stroke risk factors
      awareness, symptoms, responsiveness, and prevention behaviors were evaluated
      using a structured oral questionnaire. Binomial logistic regression analyses were
      used to identify predictors of stroke literacy. RESULTS: Although personal
      experience of stroke increased awareness of symptoms and their likeliness to
      indicate the need for urgent medical attention, only 42.7% of the respondents (n
      = 850) identified stroke as involving both blood and the brain. Educational
      attainment at or above a trade certificate, apprenticeship, or diploma increased
      the awareness of stroke symptoms compared with those with no formal educational
      attainment. Pacific Island respondents were less likely than New Zealand
      Europeans to identify a number of stroke risk factors. Maori, Pacific Island, and
      Asian respondents were less likely to identify symptoms of stroke and indicate
      the need for urgent medical attention. CONCLUSIONS: The variability in stroke
      awareness and knowledge may suggest the need to enhance stroke-related health
      literacy that facilitates understanding of risk and of factors that reduce
      morbidity and mortality after stroke in people of Maori and Pacific Island
      descent and in those with lower educational attainment or socioeconomic status.
      It is therefore important that stroke awareness campaigns include tailored
      components for target audiences.

PMID- 25847303
TI  - Upregulation of neuroglobin expression and changes in serum redox indices in a
      rat model of middle cerebral artery occlusion.
AB  - Neuroglobin (NGB) is a recently identified protein, which is localized in the
      neurons and retinal cells of the central and peripheral nervous systems in
      vertebrates. It is hypothesized to function as a scavenger for reactive oxygen
      species, or as a stress-responsive sensor for signal transduction in hypoxic
      ischemic brain insults. However, the mechanism underlying the physiological
      function of this protein remains to be elucidated. In the present study, the
      profiling of changes in the serum redox index of morphological features of the
      hippocampus and cortex, and of the expression of NGB and hypoxia-inducible factor
      1alpha (HIF-1alpha), are described in a rat middle cerebral artery occlusion
      (MCAO) model. The necrotic zone of the rat neural tissues increased in size with
      increasing reperfusion time, and different brain slices exhibited necrosis in
      different regions. The number of NGB-positive hippocampal and cortical cells, as
      well as NGB and HIF-1alpha transcript and protein levels in the ischemic cortex,
      increased with increasing reperfusion time. NGB and HIF-1alpha mRNA and protein
      levels peaked in the group that received reperfusion at 32 h after MCAO. These
      findings indicated that HIF-1alpha may be involved in ischemic pathology in an
      MCAO model and that NGB expression may be upregulated. Serum superoxide dismutase
      (SOD) activity decreased and serum malondialdehyde (MDA) levels increased with
      increasing reperfusion time, indicating that the redox potential increased
      following MCAO. Serum SOD and MDA measurements may, therefore, be useful as
      biomarkers for the early detection of ischemic injury in a clinical setting.

PMID- 25847305
TI  - Non-vitamin k antagonist oral anticoagulants do not increase cerebral
      microbleeds.
AB  - BACKGROUND: Atrial fibrillation (AF) is a cardiac arrhythmia that frequently
      induces ischemic strokes. Nowadays, non-vitamin K antagonist oral anticoagulants
      (NOACs) have come into widespread use for cardiogenic embolism prevention in
      place of warfarin. Recently, cerebral microbleeds (CMBs) have been noticed for
      their potential implication in cerebral small vessel disease. We hypothesized
      that NOACs do not have an unfavorable influence over cerebral small vessels and
      investigated whether NOACs increase CMBs in AF patients in a prospective manner.
      METHODS: We performed baseline magnetic resonance imaging (MRI) examinations on
      the 69 enrolled AF patients and re-examined second round of MRI 1 year later. The
      enrolled patients continued the same anticoagulation therapy during the meantime.
      RESULTS: CMBs did not develop in the 23 patients with NOACs for 1 year. Nine
      patients with antiplatelets also did not develop CMBs. On the other hand, 3 of 21
      patients continued on warfarin and 3 of 9 with warfarin and antiplatelets had
      CMBs. When divided into 2 groups according to whether the CMBs developed,
      significant differences in the incidence of using NOACs were observed between the
      2 groups (P = .02). A multivariate regression analysis showed that warfarin was
      independently related to the new development of CMBs (hazard ratio, 10.75; 95%
      confidence interval, 1.22-94.99; P = .03). CONCLUSIONS: This is the first report
      to clarify that NOACs do not increase CMBs in AF patients longitudinally in 1
      year. Further consideration will be continued with a much longer follow-up in
      large samples.

PMID- 25847307
TI  - Astrocytic mGluR5 and the tripartite synapse.
AB  - In the brain, astrocytes occupy a key position between vessels and synapses.
      Among their numerous functions, these glial cells are key partners of neurons
      during synaptic transmission. Astrocytes detect transmitter release through
      receptors and transporters at the level of their processes, which are in close
      proximity to the tow neuronal elements of synapses. In response to transmitter
      mediated activation, glial cells in turn regulate synaptic transmission and
      neuronal excitability. This process has been reported to involve several glial
      receptors. One of the best known of such receptors is the metabotropic
      glutamatergic receptor subtype 5 (mGluR5). In the present review we will discuss
      the implication of mGluR5s as detectors of synaptic transmission. In particular,
      we will discuss how the functional properties and localization of these receptors
      permit the detection of the synaptic signal in a defined temporal window and a
      given spatial area around the synapse. Furthermore, we will review the impact of
      their activation on synaptic transmission. 

PMID- 25847309
TI  - Welcome.

PMID- 25847308
TI  - Different danger signals differently impact on microglial proliferation through
      alterations of ATP release and extracellular metabolism.
AB  - Microglia rely on their ability to proliferate in the brain parenchyma to sustain
      brain innate immunity and participate in the reaction to brain damage. We now
      studied the influence of different danger signals activating microglia, both
      internal (typified by glutamate, associated with brain damage) and external
      (using a bacterial lipopolysaccharide, LPS), on the proliferation of microglia
      cells. We found that LPS (100 ng/mL) increased, whereas glutamate (0.5 mM)
      decreased proliferation. Notably, LPS decreased whereas glutamate increased the
      extracellular levels of ATP. In contrast, LPS increased whereas glutamate
      decreased the extracellular catabolism of ATP into adenosine through ecto
      nucleotidases and ecto-5'-nucleotidase. Finally, apyrase (degrades extracellular
      ATP) abrogated glutamate-induced inhibition of microglia proliferation;
      conversely, inhibitors of ecto-nucleotidases (ARL67156 or alpha,beta-methylene
      ADP) and adenosine deaminase (degrades extracellular adenosine) abrogated the LPS
      induced increase of microglia proliferation, which was blocked by a selective A2A
      receptor antagonist, SCH58261 (50 nM). Overall, these results highlight the
      importance of the extracellular purinergic metabolism to format microglia
      proliferation and influence the spatio-temporal profile of neuroinflammation in
      different conditions of brain damage.

PMID- 25847310
TI  - Developmental status of 22 children with trisomy 18 and eight children with
      trisomy 13: implications and recommendations.
AB  - Trisomy 18 and trisomy 13 are conditions often referred to as "incompatible with
      life" or "lethal anomalies." If there is long-term survival, the outlook is
      considered "grim." Developmental status is presumed to be minimal. Yet, Baty et
      al. [1994; 49:189-194] described a variety of developmental skills in their
      sample. An additional 22 children with trisomy 18 and eight with trisomy 13 are
      described here. A range of developmental skills is noted with strengths in the
      language and communication, gross and fine motor and social-emotional domains
      including indicating preferences, exploration of objects and a range of voluntary
      mobility. These results serve to expand the knowledge base on developmental
      status for these groups and advance the need to further explore developmental
      abilities rather than focus on deficits. Avenues for future research,
      implications, and recommendations are provided.

PMID- 25847311
TI  - Linking environmental heavy metal concentrations and salinity gradients with
      metal accumulation and their effects: A case study in 3 mussel species of Vitoria
      estuary and Espirito Santo bay, Southeast Brazil.
AB  - The present study was conducted to link the heavy metal load in three species of
      mussels (Perna perna, Mytella falcata and Mytella guyanensis) from the estuaries
      and bays around Vitoria island, south-east of Brazil, with the salinity gradient
      and the heavy metal levels in the abiotic environment (including water, suspended
      particulate matter (SPM) and sediment). Primarily based on the salinity gradient,
      a total of 26 sites around Vitoria Island were selected for sampling of water,
      SPM, sediments and organisms. Besides tissue metal levels, the condition index
      and energy stores (glycogen, lipid and protein) were quantified as an indicator
      of fitness in response to metal pollution. Dissolved metals in water indicate
      that Cd and Mn content was higher along Espirito Santo Bay, while Al, Co, Cu, Cr
      and Fe were elevated in the sites with low salinity such as river mouths,
      estuarine and sewage canals. Likewise, suspended matter sampled from low salinity
      sites showed a higher heavy metal load compared to moderate and high salinity
      sites. Though mussels were sampled from different sites, the contamination for
      Cd, Cu, Fe and Mn was higher in mussels inhabiting low salinity sites (M.
      guyanensis and M. falcata) compared to P. perna, a high saline water inhabitant.
      However, a higher Zn body burden was observed for P. perna compared to Mytella
      species. Tissue Fe accumulation (but not Mn and Zn) correlated with heavy metal
      levels in suspended material for all three species, and for M. falcata this
      correlation also existed for Cd and Cu. Energy store and condition index in all
      mussels varied depending on the sampling sites and correlated with salinity
      gradient rather than tissue metal concentration. Overall, metal concentration in
      mussels did not exceed the safe levels as per the international standards for
      metals, and would be of no risk for human consumption. 

PMID- 25847306
TI  - Derivation and validation of a discharge disposition predicting model after acute
      stroke.
AB  - BACKGROUND: Discharge disposition planning is vital for poststroke patients. We
      investigated clinical factors associated with discharging patients to nursing
      homes, using the Taiwan Stroke Registry data collected from 39 major hospitals.
      METHODS: We randomly assigned 21,575 stroke inpatients registered from 2006 to
      2008 into derivation and validation groups at a 3-to-1 ratio. We used the
      derivation group to develop a prediction model by measuring cumulative risk
      scores associated with potential predictors: age, sex, hypertension, diabetes
      mellitus, heart diseases, stroke history, snoring, main caregivers, stroke types,
      and National Institutes of Health Stroke Scale (NIHSS). Probability of nursing
      home care and odds ratio (OR) of nursing home care relative to home care by
      cumulative risk scores were measured for the prediction. The area under the
      receiver operating characteristic curve (AUROC) was used to assess the model
      discrimination against the validation group. RESULTS: Except for hypertension,
      all remaining potential predictors were significant independent predictors
      associated with stroke patient disposition to nursing home care after discharge
      from hospitals. The risk sharply increased with age and NIHSS. Patients with a
      cumulative risk score of 15 or more had an OR of 86.4 for the nursing home
      disposition. The AUROC plots showed similar areas under curves for the derivation
      group (.86, 95% confidence interval [CI], .85-.87) and for the validation group
      (.84, 95% CI, .83-.86). CONCLUSIONS: The cumulative risk score is an easy-to
      estimate tool for preparing stroke patients and their family for disposition on
      discharge.

PMID- 25847312
TI  - iTRAQ analysis of hepatic proteins in free-living Mus spretus mice to assess the
      contamination status of areas surrounding Donana National Park (SW Spain).
AB  - This work aims to develop and integrate new -omics tools that would be applicable
      to different ecosystem types for a technological updating of environmental
      evaluations. We used a 2nd-generation (iTRAQ-8plex) proteomic approach to
      identify/quantify proteins differentially expressed in the liver of free-living
      Mus spretus mice from Donana National Park or its proximities. Mass spectrometry
      was performed in an LTQ Orbitrap system for iTRAQ reporter ion quantitation and
      protein identification using a Mus musculus database as reference. A prior IEF
      step improved the separation of the complex peptide mixture. Over 2000 identified
      proteins were altered, of which 118 changed by >=2.5-fold in mice from at least
      two problem sites. Part of the results obtained with the iTRAQ analysis was
      confirmed by Western blot. Over 75% of the 118 proteins were upregulated in
      animals captured at polluted sites and only 16 proteins were downregulated.
      Upregulated proteins were involved in stress response; cell proliferation and
      apoptosis; signal transduction; metastasis or tumour suppression; xenobiotic
      export or vesicular trafficking; and metabolism. The downregulated proteins, all
      potentially harmful, were classified as oncoproteins and proteins favouring
      genome instability. The iTRAQ results presented here demonstrated that the
      survival of hepatic cells is compromised in animals living at polluted sites,
      which showed deep alterations in metabolism and the signalling pathways. The
      identified proteins may be useful as biomarkers of environmental pollution and
      provide insight about the metabolic pathways and/or physiological processes
      affected by pollutants in DNP and its surrounding areas. 

PMID- 25847313
TI  - Atmospheric transport of ozone between Southern and Eastern Asia.
AB  - This study describes the effect of pollution transport between East Asia and
      South Asia on tropospheric ozone (O3) using model results from the Task Force on
      Hemispheric Transport of Air Pollution (TF HTAP). Ensemble mean O3 concentrations
      are evaluated against satellite-data and ground observations of surface O3 at
      four stations in India. Although modeled surface O3 concentrations are 1020ppb
      higher than those observed, the relative magnitude of the seasonal cycle of O3 is
      reproduced well. Using 20% reductions in regional anthropogenic emissions, we
      quantify the seasonal variations in pollution transport between East Asia and
      South Asia. While there is only a difference of 0.05 to 0.1ppb in the magnitudes
      of the regional contributions from one region to the other, O3 from East Asian
      sources affects the most densely populated parts of South Asia while Southern
      Asian sources only partly affect the populated parts of East Asia. We show that
      emission changes over East Asia between 2000 and 2010 had a larger impact on
      populated parts of South Asia than vice versa. This study will help inform future
      decisions on emission control policy over these regions. 

PMID- 25847314
TI  - Adsorption of phosphate from aqueous solutions and sewage using zirconium loaded
      okara (ZLO): Fixed-bed column study.
AB  - This study explores the potential of removing phosphorus from aqueous solutions
      and sewage by Zr(IV)-loaded okara (ZLO) in the fixed-bed column. Soybean residue
      (okara) was impregnated with 0.25M Zr(IV) solution to prepare active binding
      sites for phosphate. The effect of several factors, including flow rate, bed
      height, initial phosphorus concentration, pH and adsorbent particle size on the
      performance of ZLO was examined. The maximum dynamic adsorption capacity of ZLO
      for phosphorus was estimated to be 16.43mg/g. Breakthrough curve modeling
      indicated that Adams-Bohart model and Thomas model fitted the experimental data
      better than Yoon-Nelson model. After treatment with ZLO packed bed column, the
      effluent could meet the discharge standard for phosphorus in Australia.
      Successful desorption and regeneration were achieved with 0.2 NaOH and 0.1 HCl,
      respectively. The results prove that ZLO can be used as a promising phosphorus
      adsorbent in the dynamic adsorption system. 

PMID- 25847315
TI  - Seven-Point Subjective Global Assessment Is More Time Sensitive Than Conventional
      Subjective Global Assessment in Detecting Nutrition Changes.
AB  - BACKGROUND: It is important for nutrition intervention in malnourished patients
      to be guided by accurate evaluation and detection of small changes in the
      patient's nutrition status over time. However, the current Subjective Global
      Assessment (SGA) is not able to detect changes in a short period. The aim of the
      study was to determine whether the 7-point SGA is more time sensitive to
      nutrition changes than the conventional SGA. METHODS: In this prospective study,
      67 adult inpatients assessed as malnourished using both the 7-point SGA and
      conventional SGA were recruited. Each patient received nutrition intervention and
      was followed up after discharge. Patients were reassessed using both tools at 1,
      3, and 5 months from baseline assessment. RESULTS: It took significantly shorter
      time to see a 1-point change using the 7-point SGA compared with the conventional
      SGA (median: 1 month vs 3 months, P = .002). The likelihood of at least a 1-point
      change is 6.74 times greater in the 7-point SGA compared with the conventional
      SGA after controlling for age, sex, and medical specialties (odds ratio, 6.74;
      95% confidence interval, 2.88-15.80; P < .001). Fifty-six percent of patients who
      had no change in SGA score had changes detected using the 7-point SGA. The level
      of agreement was 100% (kappa = 1, P < .001) between the 7-point SGA and 3-point
      SGA and 83% (kappa = 0.726, P < .001) between 2 blinded assessors for the 7-point
      SGA. CONCLUSION: The 7-point SGA is more time sensitive in its response to
      nutrition changes than the conventional SGA. It can be used to guide nutrition
      intervention for patients.

PMID- 25847317
TI  - Novel Antifungal Peptides Produced by Leuconostoc mesenteroides DU15 Effectively
      Inhibit Growth of Aspergillus niger.
AB  - The ability of Leuconostoc mesenteroides DU15 to produce antifungal peptides that
      inhibit growth of Aspergillus niger was evaluated under optimum growth conditions
      of 30  degrees C for 48 h. The cell-free supernatant showed inhibitory activity
      against A. niger. Five novel peptides were isolated with the sequences GPFPL,
      YVPLF, LLHGVPLP, GPFPLEMTLGPT, and TVYPFPGPL as identified by de novo sequencing
      using PEAKS 6 software. Peptide LLHGVPLP was the only positively charged
      (cationic peptides) and peptide GPFPLEMTLGPT negatively charged (anionic),
      whereas the rest are neutral. The identified peptides had high hydrophobicity
      ratio and low molecular weights with amino acids sequences ranging from 5 to 12
      residues. The mode of action of these peptides is observed under the scanning
      electron microscope and is due to cell lysis of fungi. This work reveals the
      potential of peptides from L. mesenteroides DU15 as natural antifungal
      preservatives in inhibiting the growth of A. niger that is implicated to the
      spoilage during storage. 

PMID- 25847318
TI  - Staging for vaginal cancer.
AB  - Vaginal cancer is a rare cancer comprising about 3% of all gynecologic cancers.
      Primary vaginal cancer should be carefully assigned as spread from cervix, vulva,
      and other metastatic tumors to vagina can occur. Although vaginal cancer
      traditionally occurs in older postmenopausal women, the incidence of high-risk
      human papillomavirus (HPV)-induced cancers is increasing in younger women.
      Squamous cell carcinoma is still the most common histopathologic type followed by
      adenocarcinoma. With decreasing use of diethylstilbestrol in pregnancy, non
      diethylstilbestrol-associated cancers are described. The Federation
      Internationale de Gynecologie et d'Obstetrique (FIGO) staging of vaginal cancer
      (2009) follows the same rules as cervical cancer; it is clinically staged and
      allows the use of routine investigative modalities for staging. Although FIGO
      encourages the use of advanced imaging modalities, such as computed tomography,
      magnetic resonance imaging (MRI), and positron emission tomography (PET), to
      guide therapy, the imaging findings may not be used to change or reassign the
      stage. TNM staging is the pathologic staging system proposed by the American
      Joint Committee on Cancer, and information available from examination of the
      resected specimen, including pelvic and inguinal lymph nodes, may be used for
      staging. 

PMID- 25847319
TI  - Patients with psoriasis have insufficient knowledge of their risk of
      atherothrombotic disease and metabolic syndrome.
AB  - BACKGROUND: Knowledge is crucial to allow patients to increase their level of
      self-care. OBJECTIVES: To examine the extent to which patients with moderate to
      severe psoriasis feel informed about their disease, to investigate their level of
      knowledge about psoriasis and the associated risk of atherothrombotic disease and
      metabolic syndrome, and to assess the importance of the kind of treatment
      received and of membership of a patients' association. METHODS: In total, 218
      patients with psoriasis (mean age 45.5 years, range 18-83), who were being
      treated with methotrexate or biological drugs responded to a questionnaire.
      RESULTS: Patients were well informed about their skin disease, but were less well
      informed about their risk of atherothrombotic disease/metabolic syndrome (visual
      analogue scale values of 6.91 and 5.15, respectively). Patients' knowledge of the
      disease was reflected by 74.2-99.1% correct answers (CA). The risk of arthritis
      elicited 88% CA and of depression 41.7% CA, while the risk of atherothrombotic
      disease and metabolic syndrome produced only 11.9-15.3% CA. Patients treated with
      biological drugs had a significantly stronger sense of being more well informed
      about the risk of disease (P = 0.02) and their risks (P < 0.001) compared with
      patients treated with methotrexate. Members of a patients' association had
      significantly more knowledge than nonmembers about the risk of depression (P =
      0.01), hypertension (P = 0.001), diabetes mellitus (P = 0.01) and obesity (P =
      0.04). CONCLUSIONS: This study shows that few patients with moderate to severe
      psoriasis are aware of their increased risk of atherothrombotic disease and
      metabolic syndrome. This indicates the need for patients to be offered education
      concerning the risk and prevention of atherothrombotic disease and metabolic
      syndrome.

PMID- 25847320
TI  - Expiratory positive airway pressure (EPAP) nasal device therapy: a welcome
      addition to obstructive sleep apnea syndrome therapy.

PMID- 25847321
TI  - The impact of obstructive sleep apnea on high-sensitivity C-reactive protein in
      subjects with or without metabolic syndrome.
AB  - BACKGROUND: It is unclear whether obstructive sleep apnea (OSA) is independently
      associated with increased levels of the acute-phase reactant C-reactive protein
      (CRP). The purpose of this study was to evaluate the relationship between OSA and
      high-sensitivity CRP (hs-CRP) levels according to the presence or absence of
      metabolic syndrome (MetS). METHODS: This study recruited 245 male bus drivers
      from one transportation company in Taiwan. Each participant was evaluated by a
      polysomnography (PSG) test, blood lipids examination, and hs-CRP. Severity of OSA
      was categorized according to the apnea-hypopnea index (AHI). RESULTS: Subjects
      were categorized into severe OSA group (n = 44; 17.9 %), moderate and mild OSA
      group (n = 117; 47.8 %), and non-OSA group (n = 84; 34.3 %). AHI had a
      significant association with hs-CRP (beta = 0.125, p = 0.009) adjusting for age,
      smoking, drinking, and MetS status. Hs-CRP was elevated with severe OSA (beta =
      0.533, p = 0.005) even adjusting for BMI and MetS. Moreover, there was an
      independent effect for adjusted odds ratios (AORs) between the stratification of
      the severity for OSA and MetS. CONCLUSION: Elevated hs-CRP level is associated
      with severe OSA, independent of known confounders. The effect of OSA in CRP is
      independent of MetS was identified.

PMID- 25847322
TI  - Etiology and pathogenesis of the cohesinopathies.
AB  - Cohesin is a chromosome-associated protein complex that plays many important
      roles in chromosome function. Genetic screens in yeast originally identified
      cohesin as a key regulator of chromosome segregation. Subsequently, work by
      various groups has identified cohesin as critical for additional processes such
      as DNA damage repair, insulator function, gene regulation, and chromosome
      condensation. Mutations in the genes encoding cohesin and its accessory factors
      result in a group of developmental and intellectual impairment diseases termed
      'cohesinopathies.' How mutations in cohesin genes cause disease is not well
      understood as precocious chromosome segregation is not a common feature in cells
      derived from patients with these syndromes. In this review, the latest findings
      concerning cohesin's function in the organization of chromosome structure and
      gene regulation are discussed. We propose that the cohesinopathies are caused by
      changes in gene expression that can negatively impact translation. The
      similarities and differences between cohesinopathies and ribosomopathies,
      diseases caused by defects in ribosome biogenesis, are discussed. The
      contribution of cohesin and its accessory proteins to gene expression programs
      that support translation suggests that cohesin provides a means of coupling
      chromosome structure with the translational output of cells.

PMID- 25847323
TI  - Female infertility: do we forget the thyroid?

PMID- 25847325
TI  - Preexisting antigen-specific immune responses are modulated by oral KLH feeding
      in humans.
AB  - Oral tolerance is the antigen-specific inhibition of a systemic immune response
      after oral antigen uptake and well established in animal models. We recently
      showed that keyhole limpet hemocyanin (KLH) feeding modulates subsequently
      induced systemic immune responses in humans as well. In the present study, we
      investigated whether oral KLH can also modulate preexisting antigen-specific
      systemic B- and T-cell responses. We induced delayed-type hypersensitivity (DTH)
      reactions as well as systemic KLH-specific B- and T-cell responses by
      subcutaneous KLH injections. Subsequent oral KLH administration decreased the
      small proportion of antigen-specific CD4(+) T cells positive for the cytokine IL
      17 at the end of the feeding regimen even further. After reimmunization, there
      was no difference in DTH reactions and the KLH-specific B-cell responses, but KLH
      fed volunteers had an increased proportion of antigen-specific CD4(+) T cells
      positive for IL-10 and a reduced proportion of antigen-specific CD4(+) T cells
      positive for the skin-homing receptor cutaneous lymphocyte antigen and IL-2 and
      IFN-gamma. Taken together, oral KLH can modulate a preexisting systemic KLH
      specific immune response. These results suggest that feeding antigen may offer
      therapeutic strategies for the suppression of unwanted immune reactions in
      humans.

PMID- 25847324
TI  - The lung endothelin system: a potent therapeutic target with bosentan for the
      amelioration of lung alterations in a rat model of diabetes mellitus.
AB  - PURPOSE: The aim of this study is to show the effect of a new mechanism on
      endothelin (ET) receptors in the physiopathology of diabetes-related pulmonary
      injury. We tested the hypothesis that dual ET-1 receptor antagonism via bosentan
      can reverse diabetes-induced lung injury. METHODS: The rats (24 male) were
      separated into four groups: group 1 (HEALTHY): Control group; group 2 (DM):
      Streptozotocin 60 mg/kg (i.p.); group 3 (DM + BOS-1): Diabetes + bosentan 50
      mg/kg per-os; group 4 (DM + BOS-2): Diabetes + bosentan 100 mg/kg per-os. The
      bosentan treatment was initiated immediately after the onset of STZ-induced
      diabetes and continued for 6 weeks. RESULTS: In the treatment group, SOD activity
      was significantly increased, although GSH and MDA levels and TNF-alpha and TGF
      beta gene expression were decreased. Bosentan 50 mg/kg and bosentan 100 mg/kg
      showed a significantly down-regulatory effect on ET-1, ET-A, and ET-B mRNA
      expression. CONCLUSIONS: In conclusion, increased endothelin levels in the lung
      associated with diabetes may be one cause of endothelial dysfunction, cytokine
      increase, and oxidant/antioxidant imbalance in the pathogenesis of complications
      that may develop during diabetes. With its multiple effects, bosentan therapy may
      be an effective option against complications that may develop in association with
      diabetes.

PMID- 25847326
TI  - NLRP3 inflammasome is responsible for Hantavirus inducing interleukin-1beta in
      THP-1 cells.
AB  - Persistent high fever is one typical clinical symptom of hemorrhagic fever with
      renal syndrome (HFRS) and circulating interleukin-1beta (IL-1beta) is elevated
      throughout HFRS. The mechanisms responsible for viral induction of IL-1beta
      secretion are unknown. In the present study, Hantaan virus (HTNV) induced the
      secretion of IL-1beta in the human monocytic cell line THP-1. Induction of IL
      1beta by HTNV relies on the activation of caspase-1. Small hairpin RNA knockdown
      in HTNV-infected THP-1 cells indicated that nucleotide-binding domain, leucine
      rich repeat containing protein 3 (NLRP3) recruits the adaptor apoptosis
      associated speck-like protein and caspase-1 to form an NLRP3 inflammasome
      complex, crucial for the induction of IL-1beta. In HTNV-infected THP-1 cells,
      reactive oxygen species release, but not extracellular adenosine triphosphate,
      was crucial for IL-1beta production. In conclusion, Hantavirus induces the
      formation of the NLRP3 inflammasome in THP-1 cells and this may be responsible
      for the elevated IL-1beta levels in HFRS patients.

PMID- 25847327
TI  - Heterometallic 3d-4f single-molecule magnets.
AB  - The promising potential applications, such as information processing and storage
      or molecular spintronics, of single-molecule magnets (SMMs) have spurred on the
      research of new, better SMMs. In this context, lanthanide ions have been seen as
      ideal candidates for new heterometallic transition metal-lanthanide SMMs. This
      perspective reviews 3d-4f SMMs up to 2014 and highlights the most significant
      advances and challenges of the field. 

PMID- 25847328
TI  - Wild immunology.

PMID- 25847329
TI  - Rationing of health care: is there an economic rationality to it?
AB  - The point of departure of this Editorial is the fact that we all are engaged in
      self-rationing in our everyday lives. We would like to spend more money on all
      sorts of nice things and devote more time to our cherished activities. Imposed
      rationing is characteristic of wartime governments, who seek to prevent the rich
      from gobbling up the resources left by the army. Since the publication in 1987 of
      David Callahan's Setting Limits: Medical Goals in an Aging Society (Callahan,
      Setting limits: medical goals in an aging society, Simon & Schuster, New York,
      1987), rationing of health care has become a widely debated issue (the Internet
      is full of pertinent entries). While rationing has also been addressed by health
      economists, there are three puzzling observations. First, Callahan (Callahan,
      Setting limits: medical goals in an aging society, Simon & Schuster, New York,
      1987) wrote for an American audience whereas rationing was introduced by the
      British National Health Service (NHS) well before 1987, with little debate.
      Second, the economic theory of rationing had been laid out by James Tobin
      [Ectrica 20(4): 521-533, 1952] as early as 1952--but health economists seem to
      have neglected his groundwork when writing about rationing. Third, they accept
      government-imposed rationing as inevitable in the case of health care, as though
      the self-rationing alternative was unavailable. An attempt is made here to
      provide rational explanations for these puzzles.

PMID- 25847330
TI  - Development of a conceptual model of health-related quality of life among
      hepatitis C patients: A systematic review of qualitative studies.
AB  - AIM: The Food and Drug Administration guidelines emphasize that patient-reported
      outcome (PRO) instruments used in clinical trials must be developed based on a
      conceptual model, yet existing PRO instruments currently used in clinical trials
      of hepatitis C virus (HCV) patients are not based on a predetermined model. The
      purpose of this study was to identify a comprehensive list of health-related
      quality of life (HRQoL) themes that may be unique to HCV by reviewing qualitative
      research articles of HCV patients. The information collected from the review was
      used to develop a preliminary model of HRQoL in HCV patients. METHODS: Ovid
      Medline, Ovid Embase, Ovid PsycINFO and PubMed were searched for peer-reviewed
      journals from 1989 to 2012. Set inclusion/exclusion criteria were utilized with a
      focus on HRQoL among HCV patients. Eligible articles that met quality assessment
      criteria were analyzed using meta-synthesis to generate categories and themes to
      propose a conceptual model. RESULTS: Ten articles that met the
      inclusion/exclusion criteria and the quality assessment criteria were reviewed.
      Eleven themes were identified: physical symptoms, physical activities, guilt,
      stigma, emotional distress, psychological behavior, social relationship, social
      activities, work function, sexual function and cognitive function. These were
      further grouped into six HRQoL domains: physical, psychological/emotional,
      social, work, sexual and cognitive functionality. CONCLUSION: The systematic
      review and the proposed model represent a useful starting point in the critical
      appraisal of the conceptual underpinnings of PRO instruments used in HCV
      patients.

PMID- 25847331
TI  - Phenotypic plasticity in gene expression contributes to divergence of locally
      adapted populations of Fundulus heteroclitus.
AB  - We examine the interaction between phenotypic plasticity and evolutionary
      adaptation using muscle gene expression levels among populations of the fish
      Fundulus heteroclitus acclimated to three temperatures. Our analysis reveals
      shared patterns of phenotypic plasticity due to thermal acclimation as well as
      non-neutral patterns of variation among populations adapted to different thermal
      environments. For the majority of significant differences in gene expression
      levels, phenotypic plasticity and adaptation operate on different suites of
      genes. The subset of genes that demonstrate both adaptive differences and
      phenotypic plasticity, however, exhibit countergradient variation of expression.
      Thus, expression differences among populations counteract environmental effects,
      reducing the phenotypic differentiation between populations. Finally, gene-by
      environment interactions among genes with non-neutral patterns of expression
      suggest that the penetrance of adaptive variation depends on the environmental
      conditions experienced by the individual. 

PMID- 25847332
TI  - A personal reflection on social media in medicine: I stand, no wiser than before.
AB  - Social media has enabled information, communication and reach for health
      professionals. There are clear benefits to patients and consumers when health
      information is broadcast. But there are unanswered questions on professionalism,
      education, and the complex mentoring relationship between doctor and student.
      This personal perspective raises a number of questions: What is online medical
      professionalism? Can online medical professionalism be taught? Can online medical
      professionalism be enforced? Is an online presence necessary to achieve the
      highest level of clinical excellence? Is there evidence that social media is
      superior to traditional methods of teaching in medical education? Does social
      media encourage multitasking and impairment of the learning process? Are there
      downsides to the perfunctory laconic nature of social media? Does social media
      waste time that is better spent attaining clinical skills? 

PMID- 25847333
TI  - Different preparations, doses, and treatment regimens of cyclosporine A cause
      adverse effects but no robust changes in seizure thresholds in rats.
AB  - Neuronal transplantation is a promising experimental treatment approach for
      intractable epilepsies, but rejection of porcine or human cells in rodent
      epilepsy models requires adequate immunosuppression to enable long-term survival
      of xenografts. The commonly used immunosuppressive drug cyclosporine A (CsA)
      itself was suggested to affect seizure thresholds. However, putative pro- or
      anticonvulsant effects of CsA have not yet been sufficiently explored in a direct
      comparison study involving different preparations, dosages, and application
      routes. We therefore comprehensively investigated the effects of acute versus
      chronic treatment using different dosages (5mg/kg, 10mg/kg), application routes
      (i.p., s.c.), and preparations of CsA (pure substance solved in polyethoxylated
      castor oil and a ready-to-use drug additionally containing ethanol) on acute
      seizure thresholds in rats in the pentylenetetrazole seizure threshold test and
      verified the most harmless protocol in the chronic amygdala-kindling model for
      temporal lobe epilepsy. None of the CsA treatment regimens induced acute changes
      of seizure thresholds. Chronic CsA treatment also did not robustly change seizure
      thresholds. As evaluated by whole blood analyses, bioavailability of CsA was
      significantly higher after i.p. application of the ready-to-use preparation
      compared to the pure substance and compared to s.c. APPLICATION: Observed adverse
      effects differed between CsA treatment regimens and included reversible diarrhea,
      lowered body temperature, and tremor, the latter two of which were also induced
      by vehicle injections containing ethanol and/or polyethoxylated castor oil. Our
      data suggest that chronic treatment (2 weeks) with 10mg/kg CsA injected i.p. in
      the ready-to-use preparation is an appropriate protocol for use in neural
      transplantation in epilepsy research applying the presently used rat models.
      Transplantation studies in experimental epilepsy research require a careful
      assessment of putative CsA effects on seizure thresholds in the specific
      experimental settings to be used.

PMID- 25847334
TI  - Retention rates of rufinamide in pediatric epilepsy patients with and without
      Lennox-Gastaut Syndrome.
AB  - OBJECTIVE: To evaluate the effectiveness of rufinamide (RFM) in patients with
      Lennox-Gastaut Syndrome (LGS) compared to those with other epilepsy syndromes
      using time to treatment failure (retention rate) as the outcome measure. METHODS:
      In this retrospective cohort study, characteristics and outcomes of all patients
      receiving RFM in 2009 and 2010 were recorded. The primary outcome measure was RFM
      failure, defined as discontinuation of RFM or initiation of an additional
      antiepileptic therapy. The secondary outcome measure was discontinuation of RFM.
      Kaplan-Meier method survival curves were generated for time to RFM failure, for
      all patients and by the presence or absence of Lennox Gastaut Syndrome (LGS). The
      impact of age, seizure type, fast or slow drug titration, and concomitant therapy
      with valproate on retention rate were evaluated using Cox regression models.
      RESULTS: One hundred thirty-three patients were included, 39 (30%) of whom had
      LGS. For all patients, the probability of remaining on RFM without additional
      therapy was 45% at 12 months and 30% at 24 months. LGS diagnosis was an
      independent predictor of time to RFM failure (HR 0.51, 95% CI 0.31-0.83), with a
      median time to failure of 18 months in LGS compared to 6 months in all others
      (p=0.006). CONCLUSIONS: In a broad population of children with refractory
      epilepsy, around half will continue taking the medication for at least a year
      without additional therapy. Patients with LGS are two times more likely to
      continue RFM without additional therapy compared to those without LGS.

PMID- 25847335
TI  - Improving the prescription of folate to women receiving antiepileptic drugs.
AB  - In women of childbearing potential (WCP) on antiepileptic drugs (AEDs), there is
      an increased risk of teratogenicity. This can potentially be reduced with folate
      supplementation. We evaluated the rate of co-prescription of AEDs and folate to
      WCP by non-epileptologist Neurology attendings and residents before and after an
      educational intervention. During the initial 3 month survey, 54 WCP were
      prescribed >=1 AEDs. Prior to the intervention, the rate of co-prescription of
      AEDs and folate was 20.4%. This was higher when neurologists were prescribing
      AEDs for epilepsy (34.4%) versus other disorders (0%, p=0.02). In the 3 months
      following the intervention, 48 WCP received AEDs. The rate of co-prescribing
      folate increased to 64.6% (p<0.001). Neurologists treating epilepsy continued to
      be more likely to prescribe folate (86.4%) than neurologists treating other
      conditions (46.2%, p=0.006). 

PMID- 25847336
TI  - Focal seizures in children with anti-NMDA receptor antibody encephalitis.
AB  - OBJECTIVE: We investigated the electroclinical features of seizures occurring in
      children with anti-NMDA receptor antibody encephalitis. METHODS: Clinical
      features and video EEG recordings were analyzed from pediatric patients with anti
      NMDA receptor antibody encephalitis at our center over a six year period.
      RESULTS: We identified eight pediatric patients with anti-NMDA receptor antibody
      encephalitis. Video EEG captured multiple focal seizures in four patients. Ictal
      onset in all four patients consisted of a focal rhythmic sharpened 6-12Hz
      activity that subsequently spread to one or both hemispheres. When there was a
      clinical correlate, seizure semiology was limb posturing with or without
      dyscognitive features. While background abnormalities were noted at presentation
      in three cases, the initial EEG background was normal in five, including three
      patients presenting with seizures. The EEG background deteriorated with clinical
      progression. CONCLUSIONS: Focal seizures are common in pediatric patients with
      anti-NMDA receptor antibody encephalitis and have a characteristic ictal onset
      pattern. Anti-NMDA receptor antibody encephalitis should be considered in the
      differential diagnosis of a child presenting with new onset focal seizures,
      irrespective of the EEG background, especially if accompanied by dyskinesia,
      psychiatric symptoms or impaired cognition.

PMID- 25847337
TI  - Vagus nerve stimulation in children less than 3 years with medically intractable
      epilepsy.
AB  - OBJECTIVE: To describe the characteristics of children less than three years of
      age with medically intractable epilepsy, who underwent Vagus Nerve Stimulator
      (VNS) therapy at Children's Hospital of Pittsburgh between 2004 and 2011.
      METHODS: Retrospective chart review. RESULTS: Seventeen patients were identified;
      adequate follow-up was available for 15. Median follow up duration was 4.3 years
      (1.4-10.2 years). 12/15 (80%) had a known etiology for their epilepsy. All
      patients had more than 1 seizure per week prior to VNS and a history of status
      epilepticus was frequent (40%, 6/15). Five patients (33%) reported improved
      seizure frequency at one year after VNS. A normal MRI was associated with seizure
      improvement (p=0.007). No patient had status epilepticus after VNS at one-year
      follow-up. At three years after VNS, four patients had experienced status
      epilepticus with only one patient experiencing multiple episodes. Complications
      were seen in 2/15 (13%) patients and in 2/21 (9.5%) procedures. SIGNIFICANCE: A
      normal MRI was associated with seizure improvement at one year in children less
      than three years of age at the time of VNS implant. The degree of overall seizure
      reduction was modest, but the frequency of status epilepticus was decreased after
      VNS implant. VNS was tolerated well in this age group.

PMID- 25847338
TI  - Reduction of epileptiform activity by valproic acid in a mouse model of
      Alzheimer's disease is not long-lasting after treatment discontinuation.
AB  - Patients with Alzheimer's disease are at increased risk for unprovoked seizures
      and epilepsy compared with age-matched controls. Experimental evidence suggests
      that neuronal hyperexcitability and epilepsy can be triggered by amyloid-beta
      (Abeta), the main component of amyloid plaques. Previous studies demonstrated
      that the administration of an anticonvulsant and histone deacetylase inhibitor,
      valproic acid, leads to a long-lasting reduction in Abeta levels. Here we used an
      APdE9 mouse model of Alzheimer's disease with overproduction of Abeta to assess
      whether treatment with valproic acid initiated immediately after epilepsy onset
      modifies the occurrence of epileptiform activity. We also analyzed whether the
      effect is long-lasting and associated with antiamyloidogenesis and histone
      modifications. Male APdE9 mice (15 week old) received daily intraperitoneal
      injections of 30mg/kg valproic acid for 1 week. After a 3-week wash-out, the same
      animals received injections of a higher dose of valproic acid (300mg/kg) daily
      for 1 week. Long-term video-electroencephalography monitoring was performed prior
      to, during, and after the treatments. Abeta and total histone H3 and H4
      acetylation levels were measured at 1 month after the final valproic acid
      treatment. While 30mg/kg valproic acid reduced spontaneous seizures in APdE9 mice
      (p<0.05, chi-square), epileptiform discharges were not reduced. Administration of
      300mg/kg valproic acid, however, reduced epileptiform discharges in APdE9 mice
      for at least 1 week after treatment discontinuation (p<0.05, Wilcoxon test), but
      there was no consistent long-term effects on epileptiform activity after
      treatment withdrawal. Further, we found no long-lasting effect on Abeta levels
      (p>0.05, Mann-Whitney test), only a meager increase in global acetylation of
      histone H3 (p<0.05), and no effects on H4 acetylation (p>0.05). In conclusion,
      valproic acid treatment of APdE9 mice at the stage when amyloid plaques are
      beginning to develop and epileptiform activity is detected reduced the amount of
      epileptiform activity, but the effect disappeared after treatment
      discontinuation. 

PMID- 25847339
TI  - The recessive model of MRP2 G1249A polymorphism decrease the risk of drug
      resistant in Asian Epilepsy: a systematic review and meta-analysis.
AB  - ABCC2 gene polymorphisms have been shown to be associated with drug-resistant
      epilepsy. However, the published results were controversial. To comprehensively
      re-evaluate the association between ABCC2 gene polymorphisms and drug-resistant
      epilepsy in Asian, we carried out this meta-analysis, which included eight
      related studies. Studies were selected using PUBMED, Web of science, the Cochrane
      database of system reviews and Embase. Pooled odds ratio (OR) with 95% confidence
      interval (CI) was used to assess the association. Studies with 1302 drug
      resistant cases and 1563 drug-sensitive controls were included. No significant
      association was detected by combined analyses for C-24T, G-1774delG, C3972T and
      G2934A. However, significant association was found in recessive model for G1249A
      polymorphism (GG vs. GA+AA: OR=0.72, 95%CI=0.53-0.96, P=0.03), indicating the
      recessive model of G1249A in MRP2/ABCC2 might decrease the risk of drug
      resistance in Asian epilepsy. 

PMID- 25847340
TI  - "It's good to know": experiences of gene identification and result disclosure in
      familial epilepsies.
AB  - Recognition of the role of genetics in the epilepsies has increased dramatically,
      impacting on clinical practice across many epilepsy syndromes. There is limited
      research investigating the impact of gene identification on individuals and
      families with epilepsy. While research has focused on the impact of delivering
      genetic information to families at the time of diagnosis in genetic diseases more
      broadly, little is known about how genetic results in epileptic diseases
      influences people's lives many years after it has been conveyed. This study used
      qualitative methods to explore the experience of receiving a genetic result in
      people with familial epilepsy. Interviews were conducted with individuals with
      familial epilepsies in whom the underlying genetic mutation had been identified.
      Recorded interviews underwent thematic analysis. 20 individuals from three
      families with different epilepsy syndromes and causative genes were interviewed.
      Multiple generations within families were studied. The mean time from receiving
      the genetic result prior to interview was 10.9 years (range 5-14 years). Three
      major themes were identified: 1) living with epilepsy: an individual's experience
      of the severity of epilepsy in their family influenced their view. 2) Clinical
      utility of the test: participants expressed varying reactions to receiving a
      genetic result. While for some it provided helpful information and relief, others
      were not surprised by the finding given the familial context. Some valued the use
      of genetic information for reproductive decision-making, particularly in the
      setting of severely affected family members. While altruistic reasons for
      participating in genetic research were discussed, participants emphasised the
      benefit of participation to them and their families. 3) 'Talking about the family
      genes': individuals reported poor communication between family members about
      their epilepsy and its genetic implications. The results provide important
      insights into the family experience of genetic epilepsies and communication
      within families. This information can be used to inform the development of
      guidelines for genetic result disclosure and genetic counselling for individuals
      and families with epilepsies. 

PMID- 25847341
TI  - Lacosamide use in the treatment of refractory epilepsy in tuberous sclerosis
      complex.
AB  - Lacosamide (LCS) was approved by the United States Food and Drug Administration
      (FDA) in 2008 as adjunctive therapy to other anti-epileptic drugs (AEDs) to treat
      focal-onset seizures, with or without secondary generalization. Its role in the
      treatment of epilepsy in individuals with tuberous sclerosis complex (TSC) has
      yet to be determined. This study evaluates LCS treatment of focal-onset
      refractory epilepsy in patients with TSC. From November 2009 to June 2014, 46 TSC
      patients followed by a single neurologist were treated with LCS. Forty-eight
      percent were responders (seizure reduction >=50%). No significant differences
      between responders and non-responders in demographic characteristics were found.
      LCS appears to be an effective and safe treatment of refractory focal onset
      seizures in TSC. Determining the long-term tolerability and efficacy of LCS in
      TSC patients requires additional clinical experience. 

PMID- 25847342
TI  - Temporopolar blurring in temporal lobe epilepsy with hippocampal sclerosis and
      long-term prognosis after epilepsy surgery.
AB  - PURPOSE: We conducted a retrospective study in order to investigate the clinical
      significance of temporopolar grey/white matter abnormalities (GWMA) in patients
      with temporal lobe epilepsy (TLE) and unilateral hippocampal sclerosis (HS) with
      a long post-surgical follow-up. METHODS: The study comprised 122 consecutive
      patients with medically refractory TLE and unilateral HS who underwent epilepsy
      surgery and had a minimum postoperative follow-up of 5 years. Patients were
      divided into two groups, based on findings of pre-surgical MRI: group 1 with GWMA
      and 2 with normal signal and grey/white matter definition in temporal pole.
      Demographic and clinical data were reviewed and compared between groups. RESULTS:
      GWMA were found in 52.5% of patients, always ipsilateral to HS. Compared with
      group 2, group 1 patients had earlier epilepsy onset (mean, 9.3 vs 14.4 years,
      P=0.001), a higher occurrence of first seizure <=2 years of age (25.8% vs 10.5%,
      P=0.036; OR=2.96 [95% CI=1.07-8.19]), and greater prevalence of left HS (76.6% vs
      43.1%, P<0.001; OR=4.31 [95% CI=1.98-9.38]). No differences were found in gender,
      presence or type of initial precipitating injury, history of secondary
      generalized seizures, duration of epilepsy, seizure frequency before surgery,
      neuropsychological evaluation and presence or lateralization of pre-surgical
      interictal epileptiform discharges. Postoperative follow-up varied from 5 to 11.5
      years (mean 7.4) and was similar in both groups (P=0.155). The proportion of
      patients classified as seizure-free (Engel class I) at last follow-up in groups 1
      and 2 were 73.4% and 69%, respectively (P=0.689). Similarly, the percentages of
      seizure-free patients with no antiepileptic drugs at last evaluation were not
      different between groups (P=0.817). In logistic regression analysis, left HS
      (P=0.001; OR=4.166 [95% CI=1.86-9.34]) and age at epilepsy onset <=2 years
      (P=0.047; OR=3.885 [95% CI=1.86-17.50]) were independently associated with risk
      of having GWMA. CONCLUSION: GWMA are frequent findings in patients with TLE and
      HS, and may help lateralize the epileptogenic zone. Our data support the
      hypothesis that GWMA are caused by seizure-related insults during the critical
      period of cerebral myelination. GWMA did not influence the postoperative seizure
      outcome of patients with TLE and HS, even after an extended duration of post
      surgical follow-up.

PMID- 25847343
TI  - Cortical thickness, surface area and folding in patients with psychogenic
      nonepileptic seizures.
AB  - OBJECTIVE: To determine cortical thickness (CTh), cortical surface area (CSA),
      curvature and sulcal depth (SD) in patients with psychogenic nonepileptic
      seizures (PNES). METHODS: Freesurfer software was used to identify differences
      between active and control group in Cth, CSA, curvature, and SD.
      Neuropsychological tests intending to document possible frontal lobe deficit were
      applied. RESULTS: We included 37 patients with PNES (age 37.3+/-13.8; female/male
      31/6; age of disease onset 26.1+/-10.6; age of disease duration 11.1+/-11.1), and
      37 healthy controls (age 38.4; +/-12.7; female/male 26/11). No difference in CSA
      and curvature was detected between groups. Patients with PNES had increased CTh
      in the left insula, left and right medial-orbitofrontal, and left lateral
      orbitofrontal, and decreased CTh in the left and right precentral, right
      enthorinal, and right lateral-occipital region than healthy controls. SD was
      increased at the level of the left and right insula, right rostral anterior
      cingulate, right posterior cingulate, and left cuneus, and reduced at the level
      of the right and left medial-orbitofrontal sulci in patients with PNES compared
      to healthy controls. CONCLUSION: Individuals with PNES display a distinct profile
      of changes in CTh, in association with increase in SD in both insula as compared
      to controls. Our results may contribute to the understanding of the
      neurobiological background of PNES. Further research, to include replication of
      the findings and directed to understand the role of insula is needed.

PMID- 25847344
TI  - Surgical treatment for patients with symptomatic generalised seizures due to
      brain lesions.
AB  - OBJECT: To study the role of epilepsy surgery for patients with focal lesions who
      exhibited the semiology of clinically generalised seizures. METHODS: From our
      epilepsy surgery series, we identified 29 patients who underwent surgery for
      seizures, including certain types of generalised seizures, according to their
      ictal semiology. We systematically reviewed the brain imaging, video-EEG,
      surgical operation, and pathological findings data of these patients. RESULTS:
      All patients had at least one type of generalised seizure according to the
      semiology; these seizures included epileptic spasms, myoclonic seizures, tonic
      seizures, atonic seizures and atypical absence seizures. Eight patients had a
      single type of seizure, 11 patients had two types of seizures, and 10 patients
      had more than two types of seizures. In addition to symptomatic generalised
      seizures, complex partial seizures were also recorded in eight patients. In 24
      patients, the ictal semiology showed slight asymmetric movements in certain types
      of seizures. Generalised interictal epileptic discharges were recorded in 24
      patients; and generalised ictal epileptic discharges as the only EEG pattern were
      recorded in 13 patients. Intracranial recording was performed in 20 patients; 10
      of whom showed a rhythm of fast activities at the initiation of the seizures.
      Functional hemispherectomy was performed for three patients with hemispheric
      lesions. Focal resection of the epileptogenic zone was performed in 26 patients.
      The resected epileptogenic zones involved a single lobe in 10 patients, two lobes
      in 11 patients, and three lobes in 5 patients; the parietal lobe was the most
      commonly involved lobe (in 19 cases). Scar lesions (in 17 patients) were most
      commonly observed on pathological examination. At the last follow-up (mean 18+/
      8.3 months, range 12-48), 17 (58.6%) patients were seizure-free. CONCLUSIONS:
      Certain patients with local brain lesions can have seizures with specific types
      of generalised semiology. An appropriate operation may be helpful for a portion
      of these patients.

PMID- 25847345
TI  - VNS for refractory status epilepticus.
AB  - BACKGROUND: Our goal was to perform a systematic review of the literature on the
      insertion of vagal nerve stimulators (VNS) for refractory status epilepticus
      (RSE) and its impact on the control of RSE. METHODS: All articles from MEDLINE,
      BIOSIS, EMBASE, Global Health, HealthStar, Scopus, Cochrane Library, the
      International Clinical Trials Registry Platform, clinicaltrials.gov (inception to
      June 2014), reference lists of relevant articles, and gray literature were
      searched. The strength of evidence was adjudicated using both the Oxford and
      GRADE methodology by two independent reviewers (FZ and MW). RESULTS: Overall, 17
      studies were identified, with 7 manuscripts and 10 meeting abstracts. A total of
      28 patients were treated. In those with generalized RSE, 76% displayed cessation
      of RSE with VNS insertion. In cases of focal RSE, 25% responded to VNS insertion.
      Few adverse effects related to VNS insertion were described. CONCLUSIONS: We
      currently cannot recommend the use of VNS for RSE. Oxford level 4, GRADE D
      evidence exists to suggest improvement in seizure control with the use of urgent
      VNS in generalized RSE. No comments can be made on the utility of VNS in focal
      RSE. Further prospective study is warranted.

PMID- 25847346
TI  - Evaluation of amygdala pathology using (11)C-methionine positron emission
      tomography/computed tomography in patients with temporal lobe epilepsy and
      amygdala enlargement.
AB  - OBJECTIVE: The association between amygdala enlargement (AE) and temporal lobe
      epilepsy (TLE) has increasingly been reported. However, the pathology of AE
      remains poorly understood. The purpose of this study was to explore AE pathology
      using (11)C-methionine (Met) positron emission tomography (PET)/computed
      tomography (CT) in patients who have TLE with AE. MATERIALS AND METHODS: Twenty
      six TLE patients with AE and 18 TLE patients without AE underwent (11)C-Met
      PET/CT and magnetic resonance imaging (MRI). (11)C-Met uptake in amygdala was
      evaluated by both visual inspection and semi-quantitative measurement. MRI was
      assessed visually and semi-quantitatively for AE. Laterality index (LI) was
      obtained by comparing the amygdala volumes of ipsilateral and contralateral
      sides. The clinical course and histopathological findings of all patients were
      also analyzed. RESULTS: On (11)C-Met PET/CT images, visual examination detected
      increased uptake in the enlarged amygdala in 7 of 26 (27%) TLE patients with AE,
      and the results were confirmed by semi-quantitative analysis. Among six TLE
      patients with AE who underwent surgery, histopathology revealed neoplasms (low
      grade astrocytoma and gangliocytoma) in two patients and focal cortical dysplasia
      in one patient with increased (11)C-Met uptake, but non-neoplastic lesions (focal
      cortical dysplasia, vacuolar degeneration, and hamartoma) in all three patients
      with no increased (11)C-Met uptake. On MRI, volume of the affected amygdala was
      significantly larger compared to the contralateral amygdala. LI was significantly
      higher in the group with AE than in the group without AE. CONCLUSIONS: This study
      revealed that some TLE patients with AE showed increased (11)C-Met uptake in the
      enlarged amygdala. (11)C-Met PET/CT is potentially useful for the evaluation of
      AE pathology, and may provide beneficial information for appropriate decision
      making.

PMID- 25847347
TI  - Sequential prefrontal lobe volume changes and cognitive dysfunctions in children
      with Panayiotopoulos syndrome presenting with status epilepticus.
AB  - Panayiotopoulos syndrome (PS) is usually not associated with neurodevelopmental
      problems. However, neuropsychological impairments may also be present in at least
      some of the patients with PS. On the other hand, several degrees of neuronal
      damage due to status epilepticus (SE) may occur in the cortex. We prospectively
      measured frontal and prefrontal lobe volumes using three-dimensional magnetic
      resonance imaging (3D-MRI)-based volumetry in patients with PS with and without
      SE. Moreover, the neuropsychological outcome in relation to the presence of SE in
      children with PS is also discussed. We studied six patients with a final
      diagnosis of PS, including three cases with SE and cognitive
      impairments/behavioral problems (SE group) and three cases without SE (non-SE
      group). Serial 3D-MRI studies were performed five times (at onset of clinical
      symptoms and 1-4 years after onset) in both the SE and non-SE patients. All
      patients were studied with a set of Wechsler Intelligence Scale for Children,
      version III (WISC-III) or Wechsler Preschool and Primary Scale of Intelligence
      tests and the Kaufman Assessment Battery for Children (K-ABC). Growth of the
      frontal and prefrontal lobes was slightly decreased for some time after SE
      episodes in the SE patients. Moreover, the prefrontal-to-frontal lobe volume
      ratio was stagnant for some time after SE in the SE patients. The scores on the
      neuropsychological tests were decreased in the SE patients. Moreover, the average
      WISC and K-ABC scores in the SE group remained low and did not reach the levels
      of the initial examinations. Occurrence of SE in patients with PS at least in
      some patients may be associated with retarded prefrontal lobe growth, which was
      related to neuropsychological problems and ultimately, neuropsychological
      outcomes. Treatment management may be required to prevent SE as much as possible
      to achieve optimal prognosis in PS at least in some patients. 

PMID- 25847348
TI  - Epilepsy in patients with malignant middle cerebral artery infarcts and
      decompressive craniectomies.
AB  - Patients with malignant middle cerebral artery (MCA) infarctions who have
      undergone craniectomy are susceptible to the development of vascular epilepsy.
      Our objective was to study the factors that might influence the occurrence of
      seizures in this group of patients. MATERIALS AND METHODS: All patients who
      developed malignant MCA infarction and had undergone decompressive craniectomy in
      our center between November 2002 and January 2014 were evaluated. In the
      subsequent follow-up, we evaluated the clinical outcomes and attempted to
      identify the factors that were related to the occurrence of seizures. RESULTS: We
      evaluated a total of 80 patients. The median time at which the craniectomy was
      performed was 40.5h after the stroke. Seizures occurred in 47.5% of all patients.
      The mortality rate within the first week was 16%, and of those who survived 53.7%
      developed seizures; 9% of these seizures were acute symptomatic, and 44.8% were
      remote. The median onset of remote seizures was seven months, and the majority of
      these were motor seizures with generalization. Notably, the patients with
      seizures exhibited longer delays from stroke to craniectomy, greater involvements
      of the temporal lobe and a higher rate of post-craniectomy recanalization of the
      occluded artery. Regarding the timing of the surgeries, a significantly greater
      proportion of those who underwent surgery more than 42h after the stroke
      developed epilepsy (p=0.004). Logistic regression revealed that only prolonged
      delay (>42h) independently predicted the development of epilepsy (OR 5.166; IC
      95% 1.451-18.389; p=0.011). CONCLUSIONS: More than half of patients with
      malignant MCA infarcts who underwent decompressive craniectomy developed
      epilepsy. The occurrence of seizures in these patients was related to the delay
      to the performance of the craniectomy.

PMID- 25847349
TI  - Similar PDK1-AKT-mTOR pathway activation in balloon cells and dysmorphic neurons
      of type II focal cortical dysplasia with refractory epilepsy.
AB  - Dysmorphic neurons and balloon cells constitute the neuropathological hallmarks
      of type II focal cortical dysplasias (FCDs) with refractory epilepsy. The genesis
      of these cells may be critical to the histological findings in type II FCD.
      Recent work has shown enhanced activation of the mTOR cascade in both balloon
      cells and dysmorphic neurons, suggesting a common pathogenesis for these two
      neuropathological hallmarks. A direct comparative analysis of balloon cells and
      dysmorphic neurons might identify a molecular link between balloon cells and
      dysmorphic neurons. Here, we addressed whether PDK1-AKT-mTOR activation
      differentiates balloon cells from dysmorphic neurons. We used
      immunohistochemistry with antibodies against phosphorylated (p)-PDK1 (Ser241), p
      AKT (Thr308), p-AKT (Ser473), p-mTOR (Ser2448), p-P70S6K (Thr229), and p-p70S6
      kinase (Thr389) in balloon cells compared with dysmorphic neurons. Strong or
      moderate staining for components of the PDK1-AKT-mTOR signaling pathway was
      observed in both balloon cells and dysmorphic neurons. However, only a few
      pyramidal neurons displayed weak staining in control group (perilesional
      neocortex and histologically normal neocortex). Additionally, p-PDK1 (Ser241) and
      p-AKT (Thr308) staining in balloon cells were stronger than in dysmorphic
      neurons, whereas p-P70S6K (Thr229) and p-p70S6 kinase (Thr389) staining in
      balloon cells was weaker than in dysmorphic neurons. In balloon cells, p-AKT
      (Ser473) and p-mTOR (Ser2448) staining was comparable with the staining in
      dysmorphic neurons. Our data support the previously suggested pathogenic
      relationship between balloon cells and dysmorphic neurons concerning activation
      of the PDK1-AKT-mTOR, which may play important roles in the pathogenesis of type
      II FCD. Differential expression of some components of the PDK1-AKT-mTOR pathway
      between balloon cells and dysmorphic neurons may result from cell-specific gene
      expression. 

PMID- 25847350
TI  - Scopolamine-induced convulsions in fasted animals after food intake: sensitivity
      of C57BL/6J mice and Sprague-Dawley rats.
AB  - Food intake triggers convulsions in fasted BALB/c mice and Wistar albino rats
      treated with antimuscarinic drugs, scopolamine or atropine. Inbred strain studies
      have yielded considerable information regarding genetic influences on seizure
      susceptibility and factors contribute to epileptogenesis in rodents. This study,
      therefore, investigated sensitivity to antimuscarinic-induced seizures in
      C57BL/6J mice and Sprague-Dawley rats. Food deprivation for 48h in mice and 52h
      in rats did not produce strain differences in body weight loss. Fasted animals
      treated i.p. with 3mg/kg scopolamine developed convulsions after food intake. The
      incidence of convulsions was indifferent in comparison to BALB/c mice and Wistar
      albino rats. Number of animals developing stage 5 was more and onset of
      convulsions was longer in C57BL/6J mice than in BALB/c mice. Strain-related
      differences in sensitivity to seizures in C57BL/6J mice may need further
      evaluation for investigating genetic influences on scopolamine-induced seizures. 

PMID- 25847352
TI  - Should ABO-incompatible deceased liver transplantation be reconsidered?

PMID- 25847351
TI  - Cardiovascular risk factors and cognitive decline in older people with type 2
      diabetes.
AB  - AIMS/HYPOTHESIS: The aim of this work was to assess the role of well-established
      cardiovascular risk factors in the late-life cognitive decline of patients with
      type 2 diabetes. METHODS: Data from 831 participants (aged 60-75 years) attending
      the 4 year follow-up of the Edinburgh Type 2 Diabetes Study (ET2DS) were used.
      Smoking history (pack-years), BP, HbA1c, plasma glucose and cholesterol were
      determined at baseline clinics (single time measurements) and/or from serial data
      recorded on a clinical management database from diagnosis until recruitment
      ('historical' data). Principal component analysis derived a factor, g, of general
      ability from seven cognitive tests. Linear regression models of follow-up g were
      adjusted for baseline g to represent 4 year cognitive change. 'Accelerated late
      life cognitive decline' was defined as scoring in the lowest tertile of '4 year
      cognitive change' regression scores. Analyses controlled for age and sex.
      RESULTS: A baseline history of moderate/heavy smoking (>= 10 pack-years) and a 1%
      increased historical HbA1c (equivalent to an increase by 11 mmol/mol) predicted a
      64% (OR 1.64; 95% CI 1.14, 2.34; p = 0.007) and 21% (OR 1.21; 95% CI 1.00, 1.45;
      p = 0.046) increased risk of accelerated cognitive decline, respectively. When
      treated as continuous measures, higher pack-years, historical HbA1c and
      historical BP emerged as significant independent predictors of 4 year decline in
      g (standardised beta range -0.07 to -0.14; all p <= 0.05).
      CONCLUSIONS/INTERPRETATION: Increased smoking and poorer glycaemic control (with
      relatively weaker findings for BP) during the life-course were independently
      associated with accelerated late-life cognitive decline. Where possible,
      evaluation is warranted of these risk factors as targets for intervention to
      reduce the burden of cognitive impairment in diabetes.

PMID- 25847353
TI  - Personality and emotional processing: A relationship between extraversion and the
      late positive potential in adolescence.
AB  - Neuroticism and extraversion are multifaceted affective-laden personality traits
      that have been associated with major depressive disorder (MDD). Research and
      theory have argued that extraversion, and particularly its facet positive
      emotionality, is specific to MDD, while neuroticism is common across
      internalizing disorders. Converging evidence has suggested that MDD is associated
      with reduced engagement with emotional stimuli, but it remains unclear whether
      either extraversion, neuroticism, or both modulate reactivity to emotional cues.
      The late positive potential (LPP) is an event-related brain potential that is
      uniquely suited to assess engagement with emotional stimuli because it reflects
      sustained attention toward emotional content. The current study examined the LPP
      in relation to personality traits that may confer risk for depression by
      examining the relationship between the LPP and both neuroticism and extraversion
      in never-depressed adolescent girls. Specifically, 550 girls aged 13.5-15.5 with
      no lifetime history of depression completed an emotional picture-viewing task,
      and the LPP was measured in response to neutral, pleasant, and unpleasant
      pictures. Personality traits were gathered via self- and informant report.
      Results indicated that high extraversion was associated with a potentiated LPP to
      emotional pictures-and this effect was accounted for by positive emotionality in
      particular. In contrast, there was no association between the LPP and neuroticism
      or its facets. The present study is one of the first to demonstrate that
      extraversion is associated with variation in neural indices of emotional picture
      processing, similar to what has been observed among individuals with depression
      and at high risk for depression. 

PMID- 25847354
TI  - Differential innate immune responses of bovine peripheral blood leukocytes to
      Salmonella enterica serovars Dublin, Typhimurium, and Enteritidis.
AB  - The majority of Salmonella serovars cause no clinical disease in cattle, while
      some are associated with severe disease. The objective of the current study was
      to determine the innate immune responses of bovine peripheral blood leukocytes
      exposed to Salmonella enterica serovar Dublin (bovine-specific), Salmonella
      typhimurium (murine adapted, but zoonotic), and Salmonella enteritidis (poultry
      host-adapted) in 3-week-old calves. All Salmonella exposures increased cell
      surface CD14 and CD18 regardless of serovar. The greatest CD14 marker mean
      fluorescence was in monocytes and the greatest mean fluorescent of the marker
      mean was in neutrophils. Phagocytosis increased with all serovars, but was not
      different among them. Neutrophils had the greatest marker mean fluorescence for
      phagocytosis, with all serovars being equal. Oxidative burst increased in all
      serovars compared to control cells, but were not different among the serovars.
      Neutrophils and monocytes were similar in the oxidative burst, with limited
      oxidative burst detected in the primarily lymphocyte population. mRNA expression
      of TNF-alpha, IL-8, and IL-12, increased above the control cells whereas none of
      these serovars affected mRNA expression of TLR4. TNF-alpha was greatest in S.
      enterica and S. typhimurium, compared to Salmonella dublin. In contrast, IL-8 was
      expressed more in S. dublin than S. typhiurium, with S. Enteriditus intermediary.
      These results show while cell surface markers, phagocytosis, and oxidative burst
      were largely unaffected by serovar, cytokine and chemokine expression differed
      among the Salmonella serovars. It appears that internal responses of the cells
      differ, rather than cell recognition, creating pathogenicity differences among of
      the serovars, even in the neonate with developing immunity. 

PMID- 25847355
TI  - Stability and feedback levels in food web models.
AB  - Neutel & Thorne (Ecology Letters, 17:651-661, June 2014) provide an approximation
      for the leading eigenvalue of a food web community matrix involving coefficients
      of its characteristic polynomial. Though valuably incorporating three-way species
      interactions, two critical problems emerge when one considers the dimensions of
      the system, calling the approach's accuracy and precision into question. 

PMID- 25847356
TI  - Pediatric periorificial dermatitis: clinical course and treatment outcomes in 222
      patients.
AB  - BACKGROUND: Periorificial dermatitis (POD) is a rosacea-like papulopustular
      facial eruption most commonly reported in young adult women. Although POD has
      been reported in children as young as 6 months of age, there are limited data on
      the diagnosis and management of POD in pediatric cases. METHODS: All children
      diagnosed with POD at the Dermatology Clinic at the University of North Carolina
      at Chapel Hill between June 2002 and March 2014 were included in the current
      study. Information related to demographics, associated risk factors, treatment
      prescribed, adverse effects, and response to treatment were obtained from a
      retrospective analysis of medical records. RESULTS: Of the 222 children
      identified, 55.4% were female, 62.2% Caucasian, and the average age at
      presentation to the clinic was 6.6 years. Although the etiology of POD remains
      uncertain, 29.3% reported a past medical history of atopic dermatitis, 14.9%
      reported a history of asthma and 58.1% reported a history of steroid use prior to
      POD onset. Fifty-nine percent were seen at a clinic visit for follow-up at an
      average of 3.8 months. Treatment often involved combining oral azithromycin with
      topical metronidazole or sodium sulfacetamide lotion. Of the patients with
      documented follow-up, 71.8% experienced complete resolution of POD. Recurrence of
      POD occurred in children dependent on inhaled steroids or nebulizers. Adverse
      effects were minimally noted, but included pigmentary changes (1.8%), worsening
      of symptoms (1.8%), gastrointestinal upset (0.9%), irritant dermatitis (0.9%),
      and xerosis (0.5%). CONCLUSION: This study discusses the clinical diagnosis and
      management of POD in pediatric cases.

PMID- 25847358
TI  - Erratum.

PMID- 25847357
TI  - Changing profiles of pediatric epilepsy surgery candidates over time: A
      nationwide single-center experience from 1990 to 2011.
AB  - OBJECTIVE: Over the past decades, the number of epilepsy surgeries in children
      has increased and indications for surgery have broadened. We studied the changes
      in patient characteristics between 1990 and 2011 in a nationwide cohort and
      related these to seizure outcome and postoperative medication status. Second, we
      tried to identify predictors for seizure outcome after pediatric epilepsy
      surgery. METHODS: To study changes over time, we divided this retrospective
      cohort of 234 children into two consecutive time periods of 11 years, and
      statistically compared the epochs in terms of patient characteristics, surgical
      variables, complications, seizure outcome, and postoperative medication status.
      To identify predictors of postoperative seizure freedom, we performed univariable
      and multivariable logistic regression analyses. RESULTS: The number of surgeries
      per year increased from an average of 5 in the first, to 16 in the past epoch.
      Over time, significantly more surgeries were performed for malformations of
      cortical development, and more patients underwent magnetoencephalography (MEG)
      and invasive monitoring. Four percent of patients had a serious complication.
      Complete seizure freedom (Engel class IA) at 2 years after surgery was achieved
      in 74% of patients, which did not change significantly over time. The proportion
      of patients who were free from seizures and antiepileptic medication 2 years
      after surgery significantly increased from 13% to 32%. Factors predictive of
      seizure recurrence were preoperative intracranial monitoring, multilobar surgery,
      etiology, and longer duration of epilepsy before surgery. SIGNIFICANCE: Although
      more complex cases were operated over time and medication was withdrawn earlier
      after surgery, success rates at 2 years remained stable. In combination with low
      complication rates, this underscores the efficacy and safety of pediatric
      epilepsy surgery. It is important to consider epilepsy surgery early, as longer
      duration of epilepsy increased the risk of postoperative seizure recurrence.

PMID- 25847360
TI  - Prediction of Boron-Boron Triple-Bond Polymers Stabilized by Janus-Type Bis(N
      heterocyclic) Carbenes.
AB  - A class of polymeric compounds containing boron-boron triple bonds stabilized by
      N-heterocyclic biscarbenes is proposed. Since a triply bonded B2 is related to
      its third excited state, the predicted macromolecule would be composed by several
      units of an electronically excited first-row homonuclear dimer. Moreover, it is
      shown that the replacement of biscarbene with N2 or CO as spacers could change
      the bonding profile of the boron-boron units to a cumulene-like structure. Based
      on these results, different types of diboryne polymers are proposed, which could
      lead to an unprecedented set of boron materials with distinct physical
      properties. The novel diboryne macromolecules could be synthesized by the
      reaction of Janus-type biscarbenes with tetrabromodiborane, B2 Br4 , and sodium
      naphthalenide, [Na(C10 H8 )], similarly to Braunschweig's work on the room
      temperature stable boron-boron triple bond compounds (Science, 2012, 336, 1420). 

PMID- 25847359
TI  - Inferior cerebellar peduncular lesion causes a distinct vestibular syndrome.
AB  - BACKGROUND AND PURPOSE: The inferior cerebellar peduncle (ICP) contains various
      fibres to and from the cerebellum relating to the integration of the
      proprioceptive and vestibular functions. However, the full clinical features of
      isolated unilateral ICP lesions have not been defined in humans. METHODS: Eight
      consecutive patients with isolated unilateral ICP lesions at the pontine level
      (six with stroke, one with multiple sclerosis and one with brainstem
      encephalitis) received bedside neurological and neuro-otological evaluations and
      underwent laboratory tests including measurements of the subjective visual
      vertical (SVV) and ocular torsion, bithermal caloric tests and pure tone
      audiometry. RESULTS: All patients developed isolated acute vestibular syndrome
      (AVS) with ipsilesional spontaneous nystagmus (n = 7) and contralesional ocular
      tilt reaction (OTR) and/or SVV tilt (n = 7). In view of the normal head impulse
      test in all patients and skew deviation in one, our patients met the criteria for
      AVS from central lesions. Five patients showed a directional dissociation between
      the OTR/SVV tilt and body lateropulsion that fell to the lesion side whilst the
      OTR/SVVtilt was contraversive. CONCLUSIONS: A unilateral ICP lesion at the
      pontine level leads to the development of isolated AVS. However, a negative head
      impulse test and directional dissociation between OTR/SVV tilt and body
      lateropulsion may distinguish lesions involving unilateral ICP at the pontine
      level from those affecting other vestibular structures.

PMID- 25847361
TI  - Effects of ditch-buried straw return on water percolation, nitrogen leaching and
      crop yields in a rice-wheat rotation system.
AB  - BACKGROUND: Crop residue management and nitrogen loss are two important
      environmental problems in the rice-wheat rotation system in China. This study
      investigated the effects of burial of straw on water percolation, nitrogen loss
      by leaching, crop growth and yield. Greenhouse mesocosm experiments were
      conducted over the course of three simulated cropping seasons in a rice1-wheat
      rice2 rotation. RESULTS: Greater amounts of straw resulted in more water
      percolation, irrespective of crop season. Burial at 20 and 35 cm significantly
      reduced, but burial at 50 cm increased nitrogen leaching. Straw at 500 kg ha(-1)
      reduced, but at 1000 kg ha(-1) and at 1500 kg ha(-1) straw increased nitrogen
      leaching in three consecutive crop rotations. In addition, straw at 500 kg ha(-1)
      buried at 35 cm significantly increased yield and its components for both crops.
      CONCLUSIONS: This study suggests that N losses via leaching from the rice-wheat
      rotation may be reduced by the burial of the appropriate amount of straw at the
      appropriate depth. Greater amounts of buried straw, however, may promote nitrogen
      leaching and negatively affect crop growth and yields. Complementary field
      experiments must be performed to make specific agronomic recommendations.

PMID- 25847363
TI  - Restoration of hematopoiesis in a case of myelodysplastic syndrome associated
      with systemic lupus erythematosus treated with rituximab.

PMID- 25847364
TI  - T2 relaxation times are increased in Skeletal muscle of DMD but not BMD patients.
AB  - INTRODUCTION: Exon-skipping drugs in Duchenne muscular dystrophy (DMD) aim to
      restore truncated dystrophin expression, which is present in the milder Becker
      muscular dystrophy (BMD). MRI skeletal muscle T2 relaxation times as a
      representation of edema/inflammation could be quantitative outcome parameters for
      such trials. METHODS: We studied T2 relaxation times, adjusted for muscle fat
      fraction using Dixon MRI, in lower leg muscles of DMD and BMD patients and
      healthy controls. RESULTS: T2 relaxation times correlated significantly with fat
      fractions in patients only (P < 0.001). After adjusting for muscle fat, T2
      relaxation times were significantly increased in 6 muscles of DMD patients (P <
      0.01), except for the extensor digitorum longus. In BMD, T2 relaxation times were
      unchanged. CONCLUSIONS: T2 relaxation times could be a useful outcome parameter
      in exon-skipping trials in DMD but are influenced by fat despite fat suppression.
      This should be accounted for when using quantitative T2 mapping to investigate
      edema/inflammation.

PMID- 25847367
TI  - A Pandora's box of new materials-metallopolymers.

PMID- 25847362
TI  - The effects of cocaine on heart rate and electrocardiogram in zebrafish (Danio
      rerio).
AB  - Zebrafish (Danio rerio) have been used as a model organism to explore the genetic
      basis for responsiveness to addictive drugs like cocaine. However, very little is
      known about how the physiological response to cocaine is mediated in zebrafish.
      In the present study electrocardiograms (ECGs) were recorded from adult zebrafish
      treated with cocaine. Treatment with cocaine resulted in a bell-shaped dose
      response curve with a maximal change in heart rate seen using 5mg/L cocaine.
      Higher doses resulted in a higher percentage of fish showing bradycardia. The
      cocaine-induced tachycardia was blocked by co-treatment with propranolol, a beta
      adrenergic antagonist, but potentiated by co-treatment with phentolamine, an
      alpha-adrenergic antagonist. Co-treatment with atropine, a classic cholinergic
      antagonist, had no effect on cocaine-induced tachycardia. Cocaine treatment of
      adult fish changed the ECG of treated fish, inducing a dose-dependent increase in
      QT interval after adjusting for heart rate (QTc), while not affecting the PR or
      QRS intervals. The acute effects of cocaine on heart rate were examined in 5-day
      old embryos to see if zebrafish might serve as a suitable model organism to study
      possible links of embryonic physiological response to subsequent adult behavioral
      response to the drug. Cocaine treatment of 5-day old zebrafish embryos also
      resulted in a bell-shaped dose response curve, with maximal tachycardia achieved
      with 10mg/L. The response in embryonic fish was thus comparable to that in adults
      and raises the possibility that the effects of embryonic exposure to cocaine on
      the developing cardiovascular system can be effectively modeled in zebrafish. 

PMID- 25847370
TI  - Defense of Cyber Infrastructures Against Cyber-Physical Attacks Using Game
      Theoretic Models.
AB  - The operation of cyber infrastructures relies on both cyber and physical
      components, which are subject to incidental and intentional degradations of
      different kinds. Within the context of network and computing infrastructures, we
      study the strategic interactions between an attacker and a defender using game
      theoretic models that take into account both cyber and physical components. The
      attacker and defender optimize their individual utilities, expressed as sums of
      cost and system terms. First, we consider a Boolean attack-defense model, wherein
      the cyber and physical subinfrastructures may be attacked and reinforced as
      individual units. Second, we consider a component attack-defense model wherein
      their components may be attacked and defended, and the infrastructure requires
      minimum numbers of both to function. We show that the Nash equilibrium under
      uniform costs in both cases is computable in polynomial time, and it provides
      high-level deterministic conditions for the infrastructure survival. When
      probabilities of successful attack and defense, and of incidental failures, are
      incorporated into the models, the results favor the attacker but otherwise remain
      qualitatively similar. This approach has been motivated and validated by our
      experiences with UltraScience Net infrastructure, which was built to support high
      performance network experiments. The analytical results, however, are more
      general, and we apply them to simplified models of cloud and high-performance
      computing infrastructures. 

PMID- 25847371
TI  - Dissecting the phenotype of supernumerary marker chromosome 20 in a patient with
      syndromic Pierre Robin sequence: combinatorial effect of gene dosage and
      uniparental disomy.
AB  - Clinical phenotypes in individuals with a supernumerary marker chromosome (SMC)
      are mainly caused by gene dosage effects due to the genes located on the SMC. An
      additional effect may result from uniparental disomy (UPD). Consequently, the
      occurrence of UPD may be a confounding factor in identifying genotype-phenotype
      correlations in SMC syndromes. Here, we report on a patient that illustrates this
      problem; the phenotype of this patient was a consequence of a combined effect of
      gene dosage and UPD. The proband showed facial dysmorphisms, growth retardation
      and developmental delay. G-band karyotype of the proband's peripheral blood
      showed the presence of mosaic SMC. A SNP array analysis documented maternal UPD20
      and 20p duplication. It is known that maternal UPD20 causes prenatal onset growth
      retardation and feeding difficulties. By contrast, duplication of 20p causes
      facial dysmorphisms, micrognathia, cleft palate, developmental delay and
      vertebral anomalies. Our classification of the proband's phenotype showed a
      mixture of these two effects. Therefore, we suggest the routine use of genome
      wide SNP array towards the detailed genotype-phenotype correlations for SMC
      syndromes.

PMID- 25847372
TI  - Biofilms affecting progression of mild steel corrosion by Gram positive Bacillus
      sp.
AB  - The biodeterioration of metals have detrimental effects on the environment with
      economic implications. The deterioration of metals is of great concern to
      industry. In this study, mild steel coupons which were immersed in a medium
      containing Gram-positive Bacillus spp. and different nutrient sources were
      compared with the control in sterile deionized water. The weight loss of the
      coupons in the presence of Bacillus spp. alone was lower than the control and was
      further reduced when additional carbon sources, especially fructose, were added.
      The level of metal corrosion was significantly increased in the presence of
      nitrate with or without bacteria. There was a significant strong correlation
      between the weight loss and biofilm level (r =  0.64; p < 0.05). The addition of
      nitrate and Bacillus spp. produced more biofilms on the coupons and resulted in
      greater weight loss compared to that with Bacillus spp. only under the same
      conditions. However, Bacillus spp. enriched with carbon sources formed less
      biofilms and results in lower weight loss compared to that with Bacillus spp.
      only. The production of biofilm by Bacillus spp. influences the level of metal
      corrosion under different environmental conditions, thereby, supporting the
      development of a preventive strategy against corrosion. 

PMID- 25847373
TI  - NRG Oncology/RTOG 0921: A phase 2 study of postoperative intensity-modulated
      radiotherapy with concurrent cisplatin and bevacizumab followed by carboplatin
      and paclitaxel for patients with endometrial cancer.
AB  - BACKGROUND: The current study was conducted to assess acute and late adverse
      events (AEs), overall survival (OS), pelvic failure, regional failure, distant
      failure, and disease-free survival in a prospective phase 2 clinical trial of
      bevacizumab and pelvic intensity-modulated radiotherapy (IMRT) with chemotherapy
      in patients with high-risk endometrial cancer. METHODS: Patients underwent a
      hysterectomy and lymph node removal, and had >=1 of the following high-risk
      factors: grade 3 carcinoma with >50% myometrial invasion, grade 2 or 3 disease
      with any cervical stromal invasion, or known extrauterine extension confined to
      the pelvis. Treatment included pelvic IMRT and concurrent cisplatin on days 1 and
      29 of radiation and bevacizumab (at a dose of 5 mg/kg on days 1, 15, and 29 of
      radiation) followed by adjuvant carboplatin and paclitaxel for 4 cycles. The
      primary endpoint was grade >=3 AEs occurring within the first 90 days (toxicity
      was graded according to the National Cancer Institute Common Terminology Criteria
      for Adverse Events [version 4.0]). RESULTS: A total of 34 patients were accrued
      from November 2009 through December 2011, 30 of whom were eligible and received
      study treatment. Seven of 30 patients (23.3%; 1-sided 95% confidence interval,
      10.6%-36.0%) developed grade >=3 treatment-related nonhematologic toxicities
      within 90 days; an additional 6 patients experienced grade >=3 toxicities between
      90 and 365 days after treatment. The 2-year OS rate was 96.7% and the disease
      free survival rate was 79.1%. No patient developed a within-field pelvic failure
      and no patients with International Federation of Gynecology and Obstetrics stage
      I to IIIA disease developed disease recurrence after a median follow-up of 26
      months. CONCLUSIONS: Postoperative bevacizumab added to chemotherapy and pelvic
      IMRT appears to be well tolerated and results in high OS rates at 2 years for
      patients with high-risk endometrial carcinoma.

PMID- 25847374
TI  - Treatment of Periodontal Disease with an Octenidine-based Antiseptic in HIV
      positive Patients.
AB  - OBJECTIVE: To evaluate the effects of a periodontal therapy with subsequent
      application of an octenidine (OCT)-based antiseptic in HIV-positive patients
      receiving highly active antiretroviral therapy. METHODS: HIV-positive patients
      with a clinically diagnosed periodontal disease were randomly divided into two
      groups (n = 30/group). Both groups initially received a periodontal therapy.
      Patients in the OCT group additionally used an OCT-based mouthwash. Subgingival
      plaque samples and periodontal indices were analysed prior to treatment onset as
      well as one and 3 months post-treatment. RESULTS: Periodontal therapy has
      resulted in a significant decrease in the values of all periodontal indices one
      and 3 months following the therapy completion (P = 0.000). The effects of the two
      applied therapeutic protocols differed significantly in terms of the variation in
      the PBI (F = 4.617; P = 0.017) and the PD (F = 3.203; P = 0.044) value. In the
      patients in the OCT group, a more pronounced decrease in the PBI and PD was noted
      at 1-month follow-up as well as a greater increase in the PD value 3 months upon
      treatment completion. In the OCT group, no more atypical microorganisms were
      detectable 1 month post-treatment, while in the control group they were found in
      34.5% of patients. CONCLUSIONS: The periodontal therapy bears good results in HIV
      positive patients. Additional administration of OCT contributes to the
      significant decline in the PBI and DS values and eliminates atypical
      microorganisms within 1 month post-treatment. However, more favourable results
      were not noted in the OCT group at the 3-month assessment.

PMID- 25847375
TI  - Reply: To PMID 25420698.

PMID- 25847376
TI  - Post-weaning parental care increases fitness but is not heritable in North
      American red squirrels.
AB  - Most empirical attempts to explain the evolution of parental care have focused on
      its costs and benefits (i.e. fitness consequences). In contrast, few
      investigations have been made of the other necessary prerequisite for
      evolutionary change, inheritance. Here, we examine the fitness consequences and
      heritability (h(2)) of a post-weaning parental care behaviour (territory
      bequeathal) in a wild population of North American red squirrels. Each year, a
      subset (average across all years = 19%) of reproductive females bequeathed their
      territory to a dependent offspring. Bequeathing females experienced higher annual
      reproductive success and did not suffer a survival cost to themselves relative to
      those females retaining their territory. Bequeathing females thus realized higher
      relative annual fitness [omega = 1.18 +/- 0.03 (SE)] than nonbequeathing females
      [omega = 0.96 +/- 0.02 (SE)]. Additive genetic influences on bequeathal
      behaviour, however, were not significantly different from 0 (h(2) = 1.9 * 10(-3);
      95% highest posterior density interval = 3.04 * 10(-8) to 0.37) and, in fact,
      bequeathal behaviour was not significantly repeatable (R = 2.0 * 10(-3); 95% HPD
      interval = 0-0.27). In contrast, directional environmental influences were
      apparent. Females were more likely to bequeath in years following low food
      abundance and when food availability in the upcoming autumn was high. Despite an
      evident fitness benefit, a lack of heritable genetic variance will constrain
      evolution of this trait.

PMID- 25847382
TI  - Rapid detection of active human cytomegalovirus infection in pregnancy using loop
      mediated isothermal amplification.
AB  - Understanding the association between congenital human cytomegalovirus (HCMV)
      infection and active maternal HCMV infection during pregnancy is important for
      maternal and neonatal healthcare. In the present study, a loop-mediated
      isothermal amplification (LAMP) method was established for the detection of CMV
      DNA from whole blood or amniotic fluid samples, using reverse transcription
      quantitative polymerase chain reaction. The results of the present study
      demonstrated that the CMV LAMP assay detection was specific for CMV DNA, whereas
      it did not detect viral DNA from herpes simplex type 1 (HSV-1), HSV-2, varicella
      zoster virus, HSV-6 or HSV-7. Sensitivity determination using serially-diluted
      CMV glycoprotein B-containing plasmids, demonstrated that >10 copies per tube
      were detectable using the CMV LAMP method. Furthermore, the detection results,
      using the LAMP method for 336 whole blood samples, demonstrated that at a
      threshold of 10(1)-10(4) copies per tube, the sensitivity of this method was
      86.96-100%, the specificity was 97.24-100%, the positive predictive value was
      76.92-100% and the negative predictive value was 99.05-100%. The results for 11
      amniotic fluid samples from pregnant women with whole blood CMV-positive and 15
      control amniotic fluid samples, indicated that the CMV LAMP assay was sensitive
      and specific for CMV detection. In conclusion, in the present study, a CMV LAMP
      method was developed, which was shown to be sensitive, specific and efficient in
      the detection of HCMV infection. Furthermore, CMV LAMP is capable of detecting
      active CMV infection in pregnant women. Therefore, the current study provides
      novel insights into diagnostic approaches for active CMV infection in pregnant
      women.

PMID- 25847383
TI  - In vitro osteoclast formation and resorption of silicon-substituted
      hydroxyapatite ceramics.
AB  - Materials that participate in bone remodeling at the implant/tissue interface
      represent a modern tissue engineering approach with the aim of balancing implant
      resorption and nascent tissue formation. Silicon-substituted hydroxyapatite
      (SiHA) ceramics are capable of stimulating new bone formation, but little is
      known about their interaction with osteoclasts (OC). The effects of soluble
      silicate and SiHA on OCs were investigated in this study. Soluble silicate below
      500 MUM did not stimulate cell metabolism at 4 days or alter resorption area at 7
      days on calcium phosphate discs. On sintered ceramics, OC numbers were similar on
      HA, Si0.3 HA (0.5 wt % Si) and Si0.5 HA (1.2 wt % Si) after 21 days in vitro, but
      actin ring sealing zone morphology on SiHA resembled that commonly found on bone
      or on carbonate-substituted hydroxyapatite (CHA). Smaller and thicker actin rings
      on SiHA as compared to HA were probably the result of altered surface chemistry
      and solubility differences. The more stable sealing zones and increased lattice
      solubility likely contributed to increased individual pit volumes observed on
      Si0.5 HA. The delayed formation of OCs on Si0.5 HA (lower numbers at day 14)
      excludes earlier differentiation as a possible mechanism of increased individual
      OC pit volumes at later times (day 21). Materials characterization of Si
      containing biomaterials remains paramount as the Si type and amounts can
      subsequently impact downstream OC behaviour in a complex manner.

PMID- 25847384
TI  - A functional perspective of nitazoxanide as a potential anticancer drug.
AB  - Cancer is a group of diseases characterized by uncontrolled cell proliferation,
      evasion of cell death and the ability to invade and disrupt vital tissue
      function. The classic model of carcinogenesis describes successive clonal
      expansion driven by the accumulation of mutations that eliminate restraints on
      proliferation and cell survival. It has been proposed that during cancer's
      development, the loose-knit colonies of only partially differentiated cells
      display some unicellular/prokaryotic behavior reminiscent of robust ancient life
      forms. The seeming "regression" of cancer cells involves changes within metabolic
      machinery and survival strategies. This atavist change in physiology enables
      cancer cells to behave as selfish "neo-endo-parasites" that exploit the tumor
      stromal cells in order to extract nutrients from the surrounding
      microenvironment. In this framework, it is conceivable that anti-parasitic
      compounds might serve as promising anticancer drugs. Nitazoxanide (NTZ), a
      thiazolide compound, has shown antimicrobial properties against anaerobic
      bacteria, as well as against helminths and protozoa. NTZ has also been
      successfully used to promote Hepatitis C virus (HCV) elimination by improving
      interferon signaling and promoting autophagy. More compelling however are the
      potential anti-cancer properties that have been observed. NTZ seems to be able to
      interfere with crucial metabolic and pro-death signaling such as drug
      detoxification, unfolded protein response (UPR), autophagy, anti-cytokine
      activities and c-Myc inhibition. In this article, we review the ability of NTZ to
      interfere with integrated survival mechanisms of cancer cells and propose that
      this compound might be a potent addition to the current chemotherapeutic strategy
      against cancer. 

PMID- 25847385
TI  - Mechanistic perspectives on cancer chemoprevention/chemotherapeutic effects of
      thymoquinone.
AB  - The bioactive natural products (plant secondary metabolites) are widely known to
      possess therapeutic value for the prevention and treatment of various chronic
      diseases including cancer. Thymoquinone (2-methyl-5-isopropyl-1,4-benzoquinone;
      TQ), a monoterpene present in black cumin seeds, exhibits pleiotropic
      pharmacological activities including antioxidant, anti-inflammatory, antidiabetic
      and antitumor effects. TQ inhibits experimental carcinogenesis in a wide range of
      animal models and has been shown to arrest the growth of various cancer cells in
      culture as well as xenograft tumors in vivo. The mechanistic basis of anticancer
      effects of TQ includes the inhibition of carcinogen metabolizing enzyme activity
      and oxidative damage of cellular macromolecules, attenuation of inflammation,
      induction of cell cycle arrest and apoptosis in tumor cells, blockade of tumor
      angiogenesis, and suppression of migration, invasion and metastasis of cancer
      cells. TQ shows synergistic and/or potentiating anticancer effects when combined
      with clinically used chemotherapeutic agents. At the molecular level, TQ targets
      various components of intracellular signaling pathways, particularly a variety of
      upstream kinases and transcription factors, which are aberrantly activated during
      the course of tumorigenesis. 

PMID- 25847386
TI  - Zirconium catalysed intermolecular hydroamination reactions of secondary amines
      with alkynes.
AB  - An in situ generated cationic zirconium complex stabilized by an n-butylamine
      bridged bis(phenolato) ligand has been developed to catalyse hydroamination
      reactions of secondary amines, which is the first example of group 4 metal based
      catalysts capable of mediating intermolecular hydroamination reactions of N
      aryl/alkyl amines. 

PMID- 25847387
TI  - Stroke Survivors' Experiences of Physical Rehabilitation: A Systematic Review of
      Qualitative Studies.
AB  - OBJECTIVE: To report and synthesize the perspectives, experiences, and
      preferences of stroke survivors undertaking inpatient physical rehabilitation
      through a systematic review of qualitative studies. DATA SOURCES: MEDLINE,
      CINAHL, Embase, and PsycINFO were searched from database inception to February
      2014. Reference lists of relevant publications were searched. All languages were
      included. STUDY SELECTION: Qualitative studies reporting stroke survivors'
      experiences of inpatient stroke rehabilitation were selected independently by 2
      reviewers. The search yielded 3039 records; 95 full-text publications were
      assessed for eligibility, and 32 documents (31 studies) were finally included.
      Comprehensiveness and explicit reporting were assessed independently by 2
      reviewers using the consolidated criteria for reporting qualitative research
      framework. Discrepancies were resolved by consensus. DATA EXTRACTION: Data
      regarding characteristics of the included studies were extracted by 1 reviewer,
      tabled, and checked for accuracy by another reviewer. All text reported in
      studies' results sections were entered into qualitative data management software
      for analysis. DATA SYNTHESIS: Extracted texts were inductively coded and analyzed
      in 3 phases using thematic synthesis. Nine interrelated analytical themes, with
      descriptive subthemes, were identified that related to issues of importance to
      stroke survivors: (1) physical activity is valued; (2) bored and alone; (3)
      patient-centered therapy; (4) recreation is also rehabilitation; (5) dependency
      and lack of control; (6) fostering autonomy; (7) power of communication and
      information; (8) motivation needs nurturing; and (9) fatigue can overwhelm.
      CONCLUSIONS: The thematic synthesis provides new insights into stroke survivors'
      experiences of inpatient rehabilitation. Negative experiences were reported in
      all studies and include disempowerment, boredom, and frustration. Rehabilitation
      could be improved by increasing activity within formal therapy and in free time,
      fostering patients' autonomy through genuinely patient-centered care, and more
      effective communication and information. Future stroke rehabilitation research
      should take into account the experiences and preferences of stroke survivors.

PMID- 25847388
TI  - Normative Values for Grip and Pinch Strength for 6- to 19-Year-Olds.
AB  - OBJECTIVES: To provide current normative data for grip and pinch strength in
      children and young adults aged 6 to 19 years as well as to examine the effect of
      age, sex, and hand dominance on grip and pinch strength. DESIGN: Descriptive
      cross-sectional. SETTING: Two grade schools, 2 high schools, and 1 university.
      PARTICIPANTS: Participants (N=1508; 741 male students and 767 female students)
      aged 6 to 19 years. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Means
      and SDs were calculated for each strength measurement (grip, tip pinch, lateral
      pinch, palmar pinch) and stratified by age and sex. Analysis of covariance and 2
      sample t tests were used to analyze the data. RESULTS: The analyses demonstrated
      that age and sex had a significant effect on hand strength values, as evidenced
      by increasing hand strength with age as well as greater hand strength in males
      than in females. Hand dominance was not shown to have a significant effect on
      hand strength. The results of this study were statistically significantly
      different from previously published normative values, with most hand strength
      values being lower than those published 28 years ago. CONCLUSIONS: Having updated
      normative data are paramount for rehabilitation practitioners to compare the grip
      and pinch strength of their clients with the average values to objectively assess
      impairment and tracking progress. The statistical significance observed for most
      data collected in this study as compared with those previously published supports
      the need for continually updating normative data.

PMID- 25847389
TI  - Crif1 Promotes Adipogenic Differentiation of Bone Marrow Mesenchymal Stem Cells
      After Irradiation by Modulating the PKA/CREB Signaling Pathway.
AB  - Dysfunction of the hematopoietic microenvironment is the main obstacle
      encountered during hematopoiesis reconstruction in patients with acute
      hematopoietic radiation syndrome. Bone marrow mesenchymal stem cells (BM-MSCs)
      play a crucial supporting role in hematopoiesis by maintaining the balance
      between adipogenic and osteogenic differentiation. In this study, we found that
      irradiation decreased the colony-forming efficiency of BM-MSCs and impaired the
      balance between adipogenic and osteogenic differentiation. Following irradiation,
      BM-MCSs became strongly predisposed to adipogenesis, as evidenced by increased
      oil red O staining and elevated mRNA and protein levels of the adipogenic markers
      and transcription factors PPARgamma and AP2. Overexpression of the essential
      adipogenesis regulator Crif1 in BM-MSCs promoted adipogenesis after irradiation
      exposure by upregulating adipogenesis-related genes, including C/EBPbeta,
      PPARgamma, and AP2. We found that Crif1 promoted the phosphorylation of cAMP
      response element binding protein (CREB) through direct interaction with protein
      kinase A (PKA)-alpha. Phosphorylation of CREB was inhibited in Crif1-knockdown BM
      MSCs even in the presence of a PKA agonist (db-cAMP) and could be suppressed in
      Crif1-overexpressing BM-MSCs by a PKAalpha inhibitor (H-89). These results
      suggest that Crif1 is an indispensable regulator of PKAalpha cat that modulates
      the PKA/CREB signaling pathway to promote adipogenic differentiation of BM-MSCs
      after irradiation.

PMID- 25847390
TI  - Simple synthesis of luminescent CdSe quantum dots from ascorbic acid and selenium
      dioxide.
AB  - A simple, low-cost and convenient method was developed for the synthesis of
      highly luminescent CdSe quantum dots (QDs) in an aqueous medium. Compared with
      previous methods, this synthesis was carried out in one pot using ascorbic acid
      (C6H8O6) to replace NaBH4 or N2H4.H2O as a reductant, and selenium dioxide to
      replace selenium or its other hazardous, expensive and unstable compounds as a
      precursor. The mechanism of CdSe QDs formation was elucidated. The influence of
      various experimental variables, including refluxing time, Cd/MSA and Cd/Se molar
      ratios, on the luminescent properties of the QDs were systematically
      investigated. X-Ray powder diffraction and transmission electron microscopy
      characterization indicated that the QDs had a pure cubic zinc-blended structure
      with a spherical shape.

PMID- 25847391
TI  - MGF enhances tenocyte invasion through MMP-2 activity via the FAK-ERK1/2 pathway.
AB  - Tendon regeneration and healing requires tenocytes to move to the repair site
      followed by proliferation and synthesis of the extracellular matrix. A novel
      synthetic growth factor, mechano-growth factor (MGF), has been discovered to have
      positive roles in tissue repair through the improvement of cell proliferation and
      migration and the protection of cells against injury-induced apoptosis. However,
      it remains unclear whether MGF has the potential to accelerate tendon repair. In
      this study, using a transwell system, we found that MGF-C25E (a synthetic mechano
      growth factor E peptide) significantly promotes tenocyte invasion, which was
      accompanied by the increased phosphorylation of focal adhesion kinase (FAK) and
      extracellular signal regulated kinase1/2 (ERK1/2) as well as the increased
      activity of matrix metalloproteinases-2 (MMP-2). The MMP-2 inhibitor OA-Hy
      blocked MGF-C25E-promoted tenocyte invasion. Inhibitors of FAK or ERK1/2 blocked
      MGF-C25E-promoted tenocyte invasion and MMP-2 activity as well. These results
      indicate that MGF-C25E promotes tenocyte invasion by increasing MMP-2 activity
      via the FAK-ERK1/2 signaling pathway. Taken together, our findings provide the
      first evidence that MGF-C25E enhances tenocyte invasion and indicate that it may
      serve as a potential repair material for promoting the healing and regeneration
      of injured tendons. 

PMID- 25847392
TI  - Predicting cumulative risk of disease onset by redistributing weights.
AB  - We propose a simple approach predicting the cumulative risk of disease
      accommodating predictors with time-varying effects and outcomes subject to
      censoring. We use a nonparametric function for the coefficient of the time
      varying effect and handle censoring through self-consistency equations that
      redistribute the probability mass of censored outcomes to the right. The
      computational procedure is extremely convenient and can be implemented by
      standard software. We prove large sample properties of the proposed estimator and
      evaluate its finite sample performance through simulation studies. We apply the
      method to estimate the cumulative risk of developing Huntington's disease (HD)
      from subjects with huntingtin gene mutation using a large collaborative HD study
      data and illustrate an inverse relationship between the cumulative risk of HD and
      the length of cytosine-adenine-guanine repeats in the huntingtin gene.

PMID- 25847393
TI  - Identification and characterization of an imidazolium by-product formed during
      the synthesis of 4-methylmethcathinone (mephedrone).
AB  - 4-Methylmethcathinone (2-methylamino-1-(4-methylphenyl)propan-1-one, mephedrone)
      is a psychoactive substance that has been associated with recreational use
      worldwide. Analytical data related to mephedrone are abundantly available but the
      characterization of by-products obtained during organic synthesis remains to be
      explored. This study presents the identification of a 1,2,3,5-tetramethyl-4-(4
      methylphenyl)-1H-imidazol-3-ium salt (TMMPI), which was formed during the
      synthesis of mephedrone. When diethyl ether was added to the crude reaction
      product, solid material precipitated from the solution. Analytical
      characterization of TMMPI employed a range of analytical techniques including
      chromatographic analysis in combination with various mass spectrometric detection
      methods, nuclear magnetic resonance spectroscopy, and crystal structure analysis.
      Additional confirmation was obtained from organic synthesis of the imidazolium by
      product. When TMMPI was subjected to analysis by gas chromatography-mass
      spectrometry (GC-MS), isomerization and degradation into two distinct compounds
      were observed, which pointed towards thermal instability under GC conditions. A
      liquid chromatography-mass spectrometry (LC-MS) based investigation into a micro
      scale synthesis of mephedrone and three additional analogues revealed that the
      corresponding TMMPI analogue was formed. Interestingly, storage of mephedrone
      freebase in a number of organic solvents also gave rise to TMMPI and it appeared
      that its formation during storage was significantly reduced in the absence of
      air. The present study aimed to support clandestine forensic investigations by
      employing analytical strategies that are applicable to manufacturing sites. The
      imidazolium salts will most likely be found amongst the waste products of any
      clandestine lab site under investigation rather than with the desired product.

PMID- 25847394
TI  - Toxocariasis: An unusual cause of pleural effusion.
AB  - Toxocara canis, one of the most frequent parasites worldwide, rarely triggers
      respiratory symptoms. We report the case of a 5-year-old girl hospitalized for a
      unilateral eosinophilic pleural effusion due to Toxocara canis. Besides the fact
      that she was living in a squat, no other medical condition was reported. There
      was no other site of infection caused by the parasite and she was successfully
      treated with albendazole. This case report is obviously unique as very few cases
      of pleural effusion due to Toxocara canis are reported in literature, all in
      adult patients.

PMID- 25847395
TI  - Roles of lymphocyte Kv1.3-channels in gut mucosal immune system: Novel
      therapeutic implications for inflammatory bowel disease.
AB  - In the gastrointestinal mucosal immune system, T-lymphocytes are activated to
      produce pro-inflammatory cytokines, and the over-activation of the lymphocytes is
      primarily responsible for the development of inflammatory bowel disease (IBD).
      Despite our understanding of the molecular involvement in the activation of
      lymphocytes, we know little about the physiological involvement. Circulating T
      lymphocytes or those derived from thymus predominantly express delayed rectifier
      K(+)-channels (Kv1.3) in their plasma membranes and these channels play crucial
      roles in inducing the lymphocyte activation and proliferation. In the
      pathogenesis of chronic renal failure, these channels, which are overexpressed in
      proliferating lymphocytes within the kidneys, are responsible for the progression
      of the disease. Since the over-activation of cellular immunity is also involved
      in the pathogenesis of IBD, T-lymphocytes in the gastrointestinal mucosa could
      share the same stimulatory mechanisms with those in the inflamed kidneys.
      Therefore, we hypothesize here that T-lymphocytes in the gastrointestinal mucosa
      would also be stimulated by the activation of the Kv1.3-channels expressed in
      their plasma membranes, and that the overexpression of the channels would
      contribute to the development of IBD. Our hypothesis is unique because it sheds
      light for the first time on a physiological mechanism by which T-lymphocytes are
      activated in the gut mucosal immune system. It is also important because our idea
      could have novel therapeutic implications for IBD, in which the over-activation
      of the lymphocytes is responsible for the pathogenesis. 

PMID- 25847396
TI  - [Cognitive and affective theory of mind in Lewy body dementia: A preliminary
      study].
AB  - INTRODUCTION: 'Theory of Mind' refers to the ability to attribute mental states,
      thoughts (cognitive component) or feelings (affective component), to others. This
      function has been studied in many neurodegenerative diseases; however, to our
      knowledge no studies investigating theory of mind in dementia with Lewy Bodies
      (DLB) have been published. The aim of our study was to search theory of mind
      deficits in patients with DLB. METHODS: Seven patients with DLB (DLB group), at
      the stage of mild dementia or mild cognitive impairments, and seven healthy
      elderly adults (control group) were included in the study. After a global
      cognitive assessment, we used the Faux Pas Recognition test to assess the
      cognitive component of theory of mind, and the Reading the Mind in the Eyes test
      for the assessment of affective component. RESULTS: We found a significant
      difference between the two groups for the Faux Pas test with an average score of
      35.6 for the DLB group and 48.3 for the control group (P=0.04). Scores were
      particularly low in the DLB group for the last question of the test concerning
      empathy (42.9% versus 85%, P=0.01). There was not a significant difference
      between the two groups for the Reading the Mind in the Eyes test (P=0.077).
      DISCUSSION: This preliminary study showed early impairments of theory of mind in
      the DLB. The cognitive component seems more affected than the affective component
      in this pathology. This pattern is consistent with the pattern found in
      Parkinson's disease, but differs from other neurodegenerative diseases as
      Alzheimer's disease or frontotemporal lobe dementia. These patterns may help to
      differentiate DLB from these diseases. Further study is needed to confirm these
      results and to compare with other dementias.

PMID- 25847397
TI  - [Mnesic disorders caused by left temporal gliomas].
AB  - Episodic memory disorders are frequent in patients with temporal lesion. Verbal
      or visuo-spatial memory disorders depend on the location and the lateralization
      of the lesion. These disorders are well described in temporal epilepsy but rarely
      in population with cerebral tumor and especially not specifically focus on
      temporal glioma. The purpose of this study was to describe neuropsychological
      examination in patient with temporal glioma in the database of the regional
      memory centre of Besancon. Four patients were identified (all right-handed and
      with a left temporal glioma). Verbal episodic memory impairment and auditory
      verbal short-term memory impairment were observed. One patient had also visual
      memory disorders. Therefore, further investigations showed an associated
      Alzheimer's disease. This finding modified the clinical management of this
      patient. Extensive neuropsychological assessment should be systematic initially
      to seek an associated pathology, especially in elderly patients, if the cognitive
      profile is unusual, during the follow-up to better understand cognitive evolution
      and the effect of therapies on cognition. 

PMID- 25847398
TI  - [Subcutaneous administration of levetiracetam in geriatrics].

PMID- 25847400
TI  - Retinal detachment following laser retinopexy.

PMID- 25847399
TI  - Quantitative proteomics of heat-treated human cells show an across-the-board mild
      depletion of housekeeping proteins to massively accumulate few HSPs.
AB  - Classic semiquantitative proteomic methods have shown that all organisms respond
      to a mild heat shock by an apparent massive accumulation of a small set of
      proteins, named heat-shock proteins (HSPs) and a concomitant slowing down in the
      synthesis of the other proteins. Yet unexplained, the increased levels of HSP
      messenger RNAs (mRNAs) may exceed 100 times the ensuing relative levels of HSP
      proteins. We used here high-throughput quantitative proteomics and targeted mRNA
      quantification to estimate in human cell cultures the mass and copy numbers of
      the most abundant proteins that become significantly accumulated, depleted, or
      unchanged during and following 4 h at 41  degrees C, which we define as mild heat
      shock. This treatment caused a minor across-the-board mass loss in many
      housekeeping proteins, which was matched by a mass gain in a few HSPs,
      predominantly cytosolic HSPCs (HSP90s) and HSPA8 (HSC70). As the mRNAs of the
      heat-depleted proteins were not significantly degraded and less ribosomes were
      recruited by excess new HSP mRNAs, the mild depletion of the many housekeeping
      proteins during heat shock was attributed to their slower replenishment. This
      differential protein expression pattern was reproduced by isothermal treatments
      with Hsp90 inhibitors. Unexpectedly, heat-treated cells accumulated 55 times more
      new molecules of HSPA8 (HSC70) than of the acknowledged heat-inducible isoform
      HSPA1A (HSP70), implying that when expressed as net copy number differences,
      rather than as mere "fold change" ratios, new biologically relevant information
      can be extracted from quantitative proteomic data. Raw data are available via
      ProteomeXchange with identifier PXD001666.

PMID- 25847401
TI  - Effect of branched-chain amino acid supplementation on functional liver
      regeneration in patients undergoing portal vein embolization and sequential
      hepatectomy: a randomized controlled trial.
AB  - BACKGROUND: Portal vein embolization (PVE) can decrease the resection ratio for
      major hepatectomy. (99m)Tc-galactosyl human serum albumin (GSA) scintigraphy is
      useful for evaluating quantitative functional liver volume. Branched chain amino
      acids (BCAAs) modulate liver function and regeneration. We analyzed the effects
      of BCAAs, in terms of liver function and regeneration after PVE, in combination
      with major hepatectomy. METHODS: This randomized controlled trial was conducted
      for patients receiving PVE through to complete hepatectomy from September, 2011
      to June, 2013. BCAA granules were added two times a day to a conventional diet in
      the BCAA administration group (BCAA group). The primary end point was functional
      liver regeneration of the future remnant liver after PVE followed by hepatic
      resection. Functional liver regeneration was assessed by the liver uptake value
      obtained from (99m)Tc-GSA scintigraphy single-photon-emission computed
      tomography/computed tomography fusion images. The secondary end points were
      volumetric liver regeneration and changes in liver function and laboratory data.
      RESULTS: A BCAA group (n = 13) and a non-BCAA group (control group; n = 15) were
      included. The primary end point was partially met: the liver uptake value
      significantly increased in the BCAA group compared with the control group 6
      months after hepatic resection (266.7% vs 77.6%, P = 0.04) and marginally
      increased after PVE (43.8% vs 17.4%, P = 0.079). Following PVE, the increment of
      the uptake ratio of the liver to the liver plus heart at 15 min was significantly
      less in the BCAA group than in the control group (0.0 and 0.01, P = 0.023).
      CONCLUSIONS: BCAA supplementation improved functional liver regeneration and
      function in patients undergoing PVE followed by major hepatic resection.

PMID- 25847402
TI  - Discovery and pharmacological characterization of a novel potent inhibitor of
      diacylglycerol-sensitive TRPC cation channels.
AB  - BACKGROUND AND PURPOSE: The cation channel transient receptor potential canonical
      (TRPC) 6 has been associated with several pathologies including focal segmental
      glomerulosclerosis, pulmonary hypertension and ischaemia reperfusion-induced lung
      oedema. We set out to discover novel inhibitors of TRPC6 channels and investigate
      the therapeutic potential of these agents. EXPERIMENTAL APPROACH: A library of
      potential TRPC channel inhibitors was designed and synthesized. Activity of the
      compounds was assessed by measuring intracellular Ca(2+) levels. The lead
      compound SAR7334 was further characterized by whole-cell patch-clamp techniques.
      The effects of SAR7334 on acute hypoxic pulmonary vasoconstriction (HPV) and
      systemic BP were investigated. KEY RESULTS: SAR7334 inhibited TRPC6, TRPC3 and
      TRPC7-mediated Ca(2+) influx into cells with IC50 s of 9.5, 282 and 226 nM,
      whereas TRPC4 and TRPC5-mediated Ca(2+) entry was not affected. Patch-clamp
      experiments confirmed that the compound blocked TRPC6 currents with an IC50 of
      7.9 nM. Furthermore, SAR7334 suppressed TRPC6-dependent acute HPV in isolated
      perfused lungs from mice. Pharmacokinetic studies of SAR7334 demonstrated that
      the compound was suitable for chronic oral administration. In an initial short
      term study, SAR7334 did not change mean arterial pressure in spontaneously
      hypertensive rats (SHR). CONCLUSIONS AND IMPLICATIONS: Our results confirm the
      role of TRPC6 channels in hypoxic pulmonary vasoregulation and indicate that
      these channels are unlikely to play a major role in BP regulation in SHR. SAR7334
      is a novel, highly potent and bioavailable inhibitor of TRPC6 channels that opens
      new opportunities for the investigation of TRPC channel function in vivo.

PMID- 25847404
TI  - Current understanding of the pathogenesis of autoimmune inner ear disease: a
      review.
AB  - BACKGROUND: Autoimmune inner ear disease (AIED) is a poorly understood form of
      sensorineural hearing loss that causes bilateral, asymmetric, progressive hearing
      loss, sometimes with vestibular symptoms, often associated with a systemic
      autoimmune disease, which is noteworthy as the only sensorineural loss responsive
      to medical therapy. Despite much research interest of the past 25 years, its
      aetiopathogenesis is still unproven. OBJECTIVE OF REVIEW: To succinctly
      consolidate research and opinion regarding the pathogenesis of autoimmune inner
      ear disease, in ongoing efforts to elucidate the molecular and intracellular
      pathways that lead to inner ear damage, which may identify new targets for
      pharmacotherapy. TYPE OF REVIEW: Systematic review SEARCH STRATEGY:
      PubMed/MEDLINE search using key terms to identify articles published between
      January 1980 and Apr 2014. Additionally, any landmark works discussed in this
      body of literature were obtained and relevant information extracted as necessary.
      EVALUATION METHOD: Inclusion criterion was any information from animal or human
      studies with information relevant to possible aetiopathogenesis of AIED. Studies
      that focused on diagnosis, ameliorating symptoms or treatment, without specific
      information relevant to mechanisms of immune-mediated injury were excluded from
      this work. Articles meeting the inclusion criteria were digested and summarised.
      RESULTS: A proposed pathogenic mechanism of AIED involves inflammation and immune
      mediated attack of specific inner ear structures, leading to an excessive Th1
      immune response with vascular changes and tissue damage in the cochlea. Studies
      have identified self-reactive T cells and immunoglobulins, and have variously
      implicated immune-complex deposition, microthrombosis and electrochemical
      disturbances causing impaired neurosignalling in the pathogenesis of AIED.
      Research has also demonstrated abnormalities in the cytokine milieu in subjects
      with AIED, which may prove a target for therapy in the future. CONCLUSION:
      Ongoing research is needed to further elucidate the aetiopathogenesis of AIED and
      discern between various mechanisms of tissue injury. Large-cohort clinical
      studies employing IL-1 receptor blockade are warranted to determine its potential
      for future therapy.

PMID- 25847403
TI  - Effect of addition of statins to antiviral therapy in hepatitis C virus-infected
      persons: Results from ERCHIVES.
AB  - 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have been
      variably noted to affect hepatitis C virus (HCV) treatment response, fibrosis
      progression, and hepatocellular carcinoma (HCC) incidence, with some having a
      more potent effect than others. We sought to determine the impact of adding
      statins to antiviral therapy upon sustained virological response (SVR) rates,
      fibrosis progression, and HCC development among HCV-infected persons using the
      Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES), an
      established, longitudinal, national cohort of HCV-infected veterans. Within
      ERCHIVES, we identified those who received HCV treatment and a follow-up of >24
      months after treatment completion. We excluded those with human immunodeficiency
      virus coinfection, hepatitis B surface antigen positivity, cirrhosis, and HCC at
      baseline. Our main outcomes were liver fibrosis progression measured by FIB-4
      scores, SVR rates, and incident HCC (iHCC). Among 7,248 eligible subjects, 46%
      received statin therapy. Statin use was significantly associated with attaining
      SVR (39.2% vs. 33.3%; P < 0.01), decreased cirrhosis development (17.3% vs.
      25.2%; P < 0.001), and decreased iHCC (1.2% vs. 2.6%; P < 0.01). Statins remained
      significantly associated with increased odds of SVR (odds ratio = 1.44; 95%
      confidence interval [CI] = 1.29, 1.61), but lower fibrosis progression rate,
      lower risk of progression to cirrhosis (hazard ratio [HR] = 0.56; 95% CI = -0.50,
      0.63), and of incident HCC (HR = 0.51; 95% CI = 0.34, 0.76) after adjusting for
      other relevant clinical factors. CONCLUSIONS: Statin use was associated with
      improved virological response (VR) rates to antiviral therapy and decreased
      progression of liver fibrosis and incidence of HCC among a large cohort of HCV
      positive Veterans. These data support the use of statins in patients with HCV.

PMID- 25847405
TI  - Time-lapse ratios of cone excitations in natural scenes.
AB  - The illumination in natural environments varies through the day. Stable
      inferences about surface color might be supported by spatial ratios of cone
      excitations from the reflected light, but their invariance has been quantified
      only for global changes in illuminant spectrum. The aim here was to test their
      invariance under natural changes in both illumination spectrum and geometry,
      especially in the distribution of shadows. Time-lapse hyperspectral radiance
      images were acquired from five outdoor vegetated and nonvegetated scenes. From
      each scene, 10,000 pairs of points were sampled randomly and ratios measured
      across time. Mean relative deviations in ratios were generally large, but when
      sampling was limited to short distances or moderate time intervals, they fell
      below the level for detecting violations in ratio invariance. When illumination
      changes with uneven geometry were excluded, they fell further, to levels obtained
      with global changes in illuminant spectrum alone. Within sampling constraints,
      ratios of cone excitations, and also of opponent-color combinations, provide an
      approximately invariant signal for stable surface-color inferences, despite
      spectral and geometric variations in scene illumination. 

PMID- 25847406
TI  - Genetic deletion of the prostaglandin E2 E prostanoid receptor subtype 3 improves
      anatomical and functional outcomes after intracerebral hemorrhage.
AB  - Intracerebral hemorrhage (ICH) is a stroke subtype associated with high mortality
      and morbidity. Following ICH, excitotoxicity and inflammation significantly
      contribute to secondary brain injury and poor outcomes. Prostaglandin E2 (PGE2 )
      levels rise locally with insult to the nervous system, and PGE2 is known to
      modulate these processes mainly through its E prostanoid (EP) receptors, EP1-4.
      EP receptor subtype 3 (EP3) is the most abundant EP receptor in the brain and we
      have previously shown that signaling through the PGE2 -EP3 axis exacerbates
      excitotoxicity and ischemic stroke outcomes. This study aimed to investigate the
      contribution of this pathway in modulating anatomical outcomes and functional
      recovery following ICH. Genetic deletion of EP3 resulted in 48.2 +/- 7.3% less
      ICH-induced brain injury (P < 0.005) and improved functional recovery (P < 0.05),
      as identified by neurological deficit scoring. To start investigating the
      mechanisms involved in neuroprotection with impaired PGE2 -EP3 signaling,
      histological staining was performed to evaluate blood and ferric iron
      accumulation, neuroinflammation, blood-brain barrier dysfunction, and peripheral
      neutrophil infiltration. After ICH, EP3 knockout mice demonstrated 49.5 +/- 8.8%
      and 42.8 +/- 13.1% less blood (P < 0.01) and ferric iron (P < 0.05),
      respectively. Furthermore, EP3 knockout mice had significantly reduced
      astrogliosis, microglial activation, blood-brain barrier breakdown, and
      neutrophil infiltration. Collectively, these results suggest an injurious role
      for the PGE2 -EP3 signaling axis in modulating brain injury, inflammation, and
      neurological functional recovery after ICH. Modulation of the PGE2 -EP3 signaling
      axis may represent a putative therapeutic avenue for the treatment of ICH.

PMID- 25847407
TI  - Recombinant lentivirus with enhanced expression of caudal-related homeobox
      protein 2 inhibits human colorectal cancer cell proliferation in vitro.
AB  - Caudal-related homeobox protein 2 (CDX2), a tumor suppressor in the adult colon,
      is overexpressed under a non-cancer specific cytomegalovirus promoter in certain
      tumor cells; furthermore, non-specific expression of CDX2 may result in aberrant
      side effects in normal cells. The human telomerase reverse transcriptase (hTERT)
      promoter is active in the majority of cancer cells but not in normal cells.
      Hypoxia is a key feature of solid tumors, and targeted genes may be significantly
      upregulated by five copies of hypoxia-response elements (HREs) under hypoxic
      conditions. However, the effect of CDX2 overexpression, as controlled by five
      copies of HREs and the hTERT promoter, on human colorectal cancer (CRC) cell
      proliferation in vitro remains to be fully elucidated. In the current study, a
      recombinant lentivirus containing the CDX2 gene under the control of five HREs
      and the hTERT promoter was generated. An immunofluorescence assay was used to
      detect CDX2 expression by the 5 HhC lentivirus, whereas an MTT assay was used to
      detect the effects of CoCl2 on the viability of LoVo cells. Western blot analysis
      was conducted in order to determine the relative ratios of recombinant CDX2
      protein to the internal control beta-actin, following 5 HhC/LoVo cell culture
      under normoxic and hypoxic conditions (100, 200, 300, 400 or 500 umol/l CoCl2)
      for 24 h, then for 12, 24 or 36 h with the optimal concentration (300 umol/l) of
      CoCl2. Reverse transcription polymerase chain reaction analysis was used to
      determine the transcription of recombinant CDX2 mRNA following culture of 5
      HhC/LoVo cells under normoxic or hypoxic conditions. Finally, a cloning assay was
      used to detect the proliferative ability of 5 HhC/LoVo and 5 Hh cells. High CDX2
      expression was observed in hTERT-positive LoVo cells under hypoxic conditions, an
      effect which was mimicked by treatment with CoCl2 to inhibit LoVo cell
      proliferation in vitro. High expression of CDX2 therefore provides a promising
      strategy for the development of novel targeted treatments and gene therapy for
      CRC.

PMID- 25847408
TI  - Herpesviruses: interfering innate immunity by targeting viral sensing and
      interferon pathways.
AB  - Type I-interferon (IFN-I) induction pathway is one of the most commonly
      stimulated signaling pathways in response to viral infection. During viral
      infection this pathway is stimulated by various pattern-recognition receptors,
      which recognize different pathogen-associated molecular patterns. The pathways
      stimulated by different pattern-recognition receptors merge into common
      transcription factors IRF3 and IRF7, lead to the production of IFN-I. The
      secreted IFN-I stimulates JAK-STAT pathway leading to induction of interferon
      stimulated genes (ISGs). The ISGs along with IFN-I create antiviral state to
      eliminate the virus from host. HHV infection enhances IFN-I-mediated innate
      antiviral response during both de novo infection and lytic reactivation from
      latency. However, HHV developed various molecular strategies to evade the sudden
      upsurge of the IFN-I and IFN-I-mediated antiviral response to establish a
      successful infection. Here, we focus on IFN-I induction and signaling pathways
      induced by three representative HHVs from each sub-family of HHV and strategies
      acquired by these HHVs to subvert the induction of IFN-I and ISGs to evade the
      host innate immunity. These fundamental understanding provides the clue for viral
      targets for pharmacological manipulation to develop potential therapeutics for
      broad subtypes of HHVs.

PMID- 25847409
TI  - Preoperative brain natriuretic peptide and atrial arrhythmias after coronary
      artery bypass graft surgery.
AB  - OBJECTIVE: To assess the association of preoperative brain natriuretic peptide
      with atrial arrhythmias and length of stay after cardiac surgery. DESIGN: A
      retrospective data analysis. SETTING: All data were collected from patients who
      underwent cardiac surgery at a single institution, an academic hospital, between
      2005 and 2010. PARTICIPANTS: Patient data were collected from the authors'
      institution's Perioperative Health Documentation System of cardiac surgeries.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The major findings were that
      individuals with a 10-pg/mL increase in brain natriuretic peptide were 1.005 (95%
      CI: 1.002, 1.009) times more likely to have an atrial arrhythmia than those with
      no increase in brain natriuretic peptide. A brain natriuretic peptide value >=306
      pg/mL was calculated to best predict an atrial arrhythmia. Those above the
      threshold were 1.455 (95% CI: 1.087, 1.947) times more likely to have an atrial
      arrhythmia than those below the threshold. Individuals above the threshold had a
      median of 3 days in the intensive care unit compared to 1 day for those below the
      threshold, as well as median hospital stays of 11 days for those below the
      threshold. CONCLUSIONS: The results indicated that elevated brain natriuretic
      peptide was associated with increased risk of atrial arrhythmias and prolonged
      length of hospital stay after cardiac surgery. Identifying at-risk patients is
      important to guide preventative strategies for postoperative atrial arrhythmias.

PMID- 25847410
TI  - Is urinary drainage necessary in patients with thoracic epidural analgesia? A
      prospective analysis: reply.

PMID- 25847411
TI  - Is urinary drainage necessary in patients with thoracic epidural analgesia? A
      prospective analysis.

PMID- 25847412
TI  - EZ-Blocker and One-Lung Ventilation via Tracheostomy.

PMID- 25847413
TI  - Quadricuspid aortic valve detected by three-dimensional transesophageal
      echocardiography.

PMID- 25847414
TI  - Improving the Quality and Safety as Well as Reducing the Cost for Patients
      Undergoing Cardiac Surgery: Missing Some Issues?

PMID- 25847415
TI  - Blood conservation strategies can be applied safely to high-risk complex aortic
      surgery.
AB  - OBJECTIVE: The present study aimed to evaluate the effect of blood conservation
      strategies on patient outcomes after aortic surgery. DESIGN: Retrospective cohort
      analysis of prospective data. SETTING: University hospital. PARTICIPANTS:
      Patients undergoing thoracic aortic surgery. INTERVENTIONS: One hundred thirty
      two consecutive high-risk patients (mean EuroSCORE 10.4%) underwent thoracic
      aortic aneurysm or dissection repair from January 2010 to September 2011. A blood
      conservation strategy (BCS) focused on limitation of hemodilution and tolerance
      of perioperative anemia was used in 57 patients (43.2%); the remaining 75 (56.8%)
      patients were managed by traditional methods. Mortality, major complications, and
      red blood cell transfusion requirements were assessed. Independent risk factors
      for clinical outcomes were determined by multivariate analyses. MEASUREMENTS AND
      MAIN RESULTS: Hospital mortality was 9.8% (13 of 132). Lower preoperative
      hemoglobin was an independent predictor of mortality (p<0.01, odds ratio [OR]
      1.7). Major complications were associated with perioperative transfusion: 0%
      complication rate in patients receiving<2 units of packed red blood cells versus
      32.3% (20 of 62) in patients receiving >=2 units. The blood conservation strategy
      had no significant impact on mortality (p = 0.4) or major complications (p = 0.9)
      despite the blood conservation patients having a higher incidence of aortic
      dissection and urgent/emergent procedures and lower preoperative and discharge
      hemoglobin. In patients with aortic aneurysms, BCS patients received 1.5 fewer
      units of red blood cells (58% reduction) than non-BCS patients (p = 0.01).
      Independent risk factors for transfusion were lower preoperative hemoglobin
      (p<0.01, OR 1.5) and lack of BCS (p = 0.02, OR 3.6). CONCLUSIONS: Clinical
      practice guidelines for blood conservation should be considered for high-risk
      complex aortic surgery patients.

PMID- 25847416
TI  - Posttraumatic stress symptoms in police staff 12-18 months after the Canterbury
      earthquakes.
AB  - Understanding posttraumatic stress disorder (PTSD) symptoms in police first
      responders is an underdeveloped field. Using a cross-sectional survey, this study
      investigated demographic and occupational characteristics, coping resources and
      processes, along with first-responder roles and consequences 18 months following
      a disaster. Hierarchical linear regression (N = 576) showed that greater symptom
      levels were significantly positively associated with negative emotional coping
      (beta = .31), a communications role (beta = .08) and distress following exposure
      to resource losses (beta = .14), grotesque scenes (beta = .21), personal harm
      (beta = .14), and concern for significant others (beta = .17). Optimism alone was
      negatively associated (beta = -.15), with the overall model being a modest fit
      (adjusted R(2) = .39). The findings highlight variables for further study in
      police.

PMID- 25847417
TI  - High plasma neurotensin levels in children with Prader-Willi syndrome.
AB  - Prader-Willi syndrome (PWS) is an obesity-related genetic condition, most
      commonly due to a paternal deletion of the chromosome 15q11-q13 region. PWS is
      characterized by growth hormone deficiency, infantile hypotonia and feeding
      problems, hypogenitalism/hypogonadism, increased pain threshold and thermal
      instability, decreased gastric motility, and hyperphagia in childhood leading to
      severe obesity. Neuro-endocrine peptides are known to influence gastric function
      and pain sensation which led us to measure a specific peptide that may be
      involved [i.e., neurotensin (NT)] in PWS and compared with unrelated control
      siblings. Overnight fasting plasma NT levels were obtained from 23 children with
      confirmed PWS (age: 8.2 +/- 2.0 years; range: 5-11 years) and 18 unaffected,
      unrelated siblings (age: 8.2 +/- 2.3 years; range: 5-11 years) and measured using
      Multiplex sandwich immunoassays with the Luminex magnetic-bead based platform.
      Plasma NT levels were natural log-transformed and analyzed by ANOVA with
      adjustments for age, gender, and body mass index (BMI). No difference was found
      in plasma NT levels for gender, age or BMI or significant correlations seen with
      age or BMI. Higher plasma NT levels (P < 0.001) were seen in PWS children (mean
      of 626 +/- 238 pg/ml) compared with unaffected, unrelated siblings (mean of 371
      +/- 236 pg/ml). Plasma levels were also higher in children with maternal disomy
      15 (736 +/- 182 pg/ml) compared with those having the deletion subtype (548 +/-
      247 pg/ml, P < 0.04). Although no measures for pain threshold, thermal
      instability or gastric motility were performed in our study participants, higher
      plasma NT levels were found in PWS children.

PMID- 25847418
TI  - Organochlorine pesticide levels in the food web in rice paddies of Bueng Boraphet
      wetland, Thailand.
AB  - The contamination by organochlorine pesticides (OCPs) of water, sediments, rice
      grains and leaves, and animals of different trophic levels, collected from rice
      paddies surrounding Bueng Boraphet wetland, central Thailand, was studied during
      November 2009 to February 2010. The levels of total
      dichlorodiphenyltrichloroethanes (SigmaDDT) were too low to be detected in any
      samples. High levels of total hexachlorocyclohexanes (SigmaHCH) and total aldrins
      (SigmaALD) and low levels of total chlordanes (SigmaCHL) were detected in both
      sediments and rice grains. alpha-HCH, beta-HCH, gamma-HCH, and aldrin in rice
      grains exceeded the acceptable limits set by the Ministry of Public Health of
      Thailand. Rice grains were at high risk of contamination due to the direct
      spraying of OCPs. Fishes were contaminated with moderate levels of aldrin.
      Continued surveys of pesticide contamination in water, sediments, and organisms
      of each trophic level are recommended to more effectively monitor and control
      agricultural pesticide usage around Bueng Boraphet wetland and to further assess
      the ecological risks and impacts on human health. 

PMID- 25847419
TI  - Temporal and spatial assessment of river surface water quality using multivariate
      statistical techniques: a study in Can Tho City, a Mekong Delta area, Vietnam.
AB  - The present study is an evaluation of temporal/spatial variations of surface
      water quality using multivariate statistical techniques, comprising cluster
      analysis (CA), principal component analysis (PCA), factor analysis (FA) and
      discriminant analysis (DA). Eleven water quality parameters were monitored at 38
      different sites in Can Tho City, a Mekong Delta area of Vietnam from 2008 to
      2012. Hierarchical cluster analysis grouped the 38 sampling sites into three
      clusters, representing mixed urban-rural areas, agricultural areas and industrial
      zone. FA/PCA resulted in three latent factors for the entire research location,
      three for cluster 1, four for cluster 2, and four for cluster 3 explaining 60,
      60.2, 80.9, and 70% of the total variance in the respective water quality. The
      varifactors from FA indicated that the parameters responsible for water quality
      variations are related to erosion from disturbed land or inflow of effluent from
      sewage plants and industry, discharges from wastewater treatment plants and
      domestic wastewater, agricultural activities and industrial effluents, and
      contamination by sewage waste with faecal coliform bacteria through sewer and
      septic systems. Discriminant analysis (DA) revealed that nephelometric turbidity
      units (NTU), chemical oxygen demand (COD) and NH3 are the discriminating
      parameters in space, affording 67% correct assignation in spatial analysis; pH
      and NO2 are the discriminating parameters according to season, assigning
      approximately 60% of cases correctly. The findings suggest a possible revised
      sampling strategy that can reduce the number of sampling sites and the indicator
      parameters responsible for large variations in water quality. This study
      demonstrates the usefulness of multivariate statistical techniques for evaluation
      of temporal/spatial variations in water quality assessment and management.

PMID- 25847420
TI  - The socio-economic significance of the Turkish coastal environment for
      sustainable development.
AB  - The objective of this study was to estimate the contribution from the coastal
      resources in the coastal region to the national economy for sustainable
      development. There was no separate data base for the coastal zone so that the
      contribution from the coastal resources in the coastal region to the national
      economy was not evaluated. In estimating the significance of Turkish coastal
      cities, indirect methods and the geographical information system were used. In
      conclusion, it was found that 61.09% of the total national gross domestic product
      and 50.75% of the national agricultural, 90.98% of the national fisheries, 68.19%
      of the national tourism and 71.82% of the national industrial gross domestic
      product came from the coastal zone. It was determined that while coastal cities
      of Turkey had 28.23% of the national surface area, the coastal district had
      12.96%; in other words, 21.5 million (28.04%) of the national population lived in
      101.5 thousand km(2) (12.96%) of the national surface area. Approximately 44% of
      the national gross domestic product comes from the top ten coastal cities.
      According to the contribution ratio to the national economy of each coastal city,
      these low-lying coastal cities have about $16 billion risk value. An analysis
      showed that the coastal zone is very important for the national economy of Turkey
      and also the pressure on the coastal zone is very high. At a time of increasing
      pressures on coastal resources of Turkey, the decision-makers need the most up-to
      date information on the full range of values these resources provide in order to
      make decisions that best reflect the public interest.

PMID- 25847422
TI  - The impact of chronic Aflatoxin B1 exposure and p53 genotype on base excision
      repair in mouse lung and liver.
AB  - Aflatoxin B1 (AFB1) is produced by species of Aspergillus, and is a known human
      carcinogen. AFB1-induced oxidative DNA damage, specifically 8-hydroxy-2
      deoxyguanosine (8-OHdG) lesions, has been demonstrated in both animal models and
      in humans, and is repaired by base excision repair (BER). The tumour suppressor
      gene p53 is implicated in the regulation of DNA repair, and heterozygous p53
      knockouts have an attenuated nucleotide excision repair response to AFB1. Male
      heterozygous p53 knockout mice and their wild-type controls were exposed to 0,
      0.2 or 1.0ppm AFB1 for 26 weeks in their diet. BER activity of lung and liver was
      assessed with an in vitro assay, using 8-OHdG-damaged plasmid DNA as a substrate.
      BER activity did not differ between livers or lungs from untreated wild-type
      versus heterozygous p53 knockout mice. In wild-type mice, repair was 65% lower in
      liver extracts from mice exposed to 1.0ppm AFB1 than in liver extracts from mice
      exposed to 0.2ppm AFB1 (p<0.05), but not significantly lower than that in liver
      extracts from control mice. AFB1 did not affect BER in lung extracts from wild
      type mice, or in lung and liver extracts from heterozygous p53 knockout mice. In
      liver and lung, AFB1 exposure did not alter levels of 8-oxoguanine glycosylase
      protein, a key enzyme in the repair of 8-OHdG, and did not cause hepatotoxicity,
      as indicated by plasma alanine aminotransferase levels. In conclusion, chronic
      exposure to AFB1 did not affect BER in lungs or livers of heterozygous p53
      knockout mice. BER activity was lower in livers from p53 wild type mice exposed
      to 1.0ppm AFB1 versus those exposed to 0.2ppm AFB1, an effect that was not
      attributable to liver cell death or altered levels of 8-oxoguanine glycosylase. 

PMID- 25847423
TI  - Kinetoplast adaptations in American strains from Trypanosoma vivax.
AB  - The mitochondrion role changes during the digenetic life cycle of African
      trypanosomes. Owing to the low abundance of glucose in the insect vector (tsetse
      flies) the parasites are dependent upon a fully functional mitochondrion, capable
      of performing oxidative phosphorylation. Nevertheless, inside the mammalian host
      (bloodstream forms), which is rich in nutrients, parasite proliferation relies on
      glycolysis, and the mitochondrion is partially redundant. In this work we perform
      a comparative study of the mitochondrial genome (kinetoplast) in different
      strains of Trypanosoma vivax. The comparison was conducted between a West African
      strain that goes through a complete life cycle and two American strains that are
      mechanically transmitted (by different vectors) and remain as bloodstream forms
      only. It was found that while the African strain has a complete and apparently
      fully functional kinetoplast, the American T. vivax strains have undergone a
      drastic process of mitochondrial genome degradation, in spite of the recent
      introduction of these parasites in America. Many of their genes exhibit different
      types of mutations that are disruptive of function such as major deletions,
      frameshift causing indels and missense mutations. Moreover, all but three genes
      (A6-ATPase, RPS12 and MURF2) are not edited in the American strains, whereas
      editing takes place normally in all (editable) genes from the African strain. Two
      of these genes, A6-ATPase and RPS12, are known to play an essential function
      during bloodstream stage. Analysis of the minicircle population shows that its
      diversity has been greatly reduced, remaining mostly those minicircles that carry
      guide RNAs necessary for the editing of A6-ATPase and RPS12. The fact that these
      two genes remain functioning normally, as opposed to that reported in Trypanosoma
      brucei-like trypanosomes that restrict their life cycle to the bloodstream forms,
      along with other differences, is indicative that the American T. vivax strains
      are following a novel evolutionary pathway. 

PMID- 25847421
TI  - TP53 mutations induced by BPDE in Xpa-WT and Xpa-Null human TP53 knock-in (Hupki)
      mouse embryo fibroblasts.
AB  - Somatic mutations in the tumour suppressor gene TP53 occur in more than 50% of
      human tumours; in some instances exposure to environmental carcinogens can be
      linked to characteristic mutational signatures. The Hupki (human TP53 knock-in)
      mouse embryo fibroblast (HUF) immortalization assay (HIMA) is a useful model for
      studying the impact of environmental carcinogens on TP53 mutagenesis. In an
      effort to increase the frequency of TP53-mutated clones achievable in the HIMA,
      we generated nucleotide excision repair (NER)-deficient HUFs by crossing the
      Hupki mouse with an Xpa-knockout (Xpa-Null) mouse. We hypothesized that
      carcinogen-induced DNA adducts would persist in the TP53 sequence of Xpa-Null
      HUFs leading to an increased propensity for mismatched base pairing and mutation
      during replication of adducted DNA. We found that Xpa-Null Hupki mice, and HUFs
      derived from them, were more sensitive to the environmental carcinogen
      benzo[a]pyrene (BaP) than their wild-type (Xpa-WT) counterparts. Following
      treatment with the reactive metabolite of BaP, benzo[a]pyrene-7,8-diol-9,10
      epoxide (BPDE), Xpa-WT and Xpa-Null HUF cultures were subjected to the HIMA. A
      significant increase in TP53 mutations on the transcribed strand was detected in
      Xpa-Null HUFs compared to Xpa-WT HUFs, but the TP53-mutant frequency overall was
      not significantly different between the two genotypes. BPDE induced mutations
      primarily at G:C base pairs, with approximately half occurring at CpG sites, and
      the predominant mutation type was G:C>T:A in both Xpa-WT and Xpa-Null cells.
      Further, several of the TP53 mutation hotspots identified in smokers' lung cancer
      were mutated by BPDE in HUFs (codons 157, 158, 245, 248, 249, 273). Therefore,
      the pattern and spectrum of BPDE-induced TP53 mutations in the HIMA are
      consistent with TP53 mutations detected in lung tumours of smokers. While Xpa
      Null HUFs exhibited increased sensitivity to BPDE-induced damage on the
      transcribed strand, NER-deficiency did not enhance TP53 mutagenesis resulting
      from damage on the non-transcribed strand in this model. 

PMID- 25847424
TI  - Dynamic alteration in H3 serine 10 phosphorylation is G1-phase specific during
      ionization radiation induced DNA damage response in human cells.
AB  - Chromatin acts as a natural barrier in DNA-damage recognition and repair.
      Histones undergo differential post-translational modification(s) to facilitate
      DNA damage response (DDR). Importance of modifications like phosphorylation of
      histone variant H2A.X in DNA repair is very well understood, however, ambiguous
      results exist in literature regarding the levels of certain histone modifications
      and their possible role in repair. In the present study, we have investigated in
      depth the alteration in the level of the highly dynamic histone mark H3S10P as it
      plays a dual role in different phases of the cell cycle. We show here that H3S10P
      decreases specifically from irradiated G1-enriched cells irrespective of the
      damaging agent or the cell line used in the study. Interestingly, the loss occurs
      predominantly from H3.3 variant which is a transcription activation mark like
      H3S10P itself, suggesting that the alteration might be implicated in
      transcription repression. The decrease in other transcription marks like H3K9Ac,
      H3K14Ac, H3K56Ac and H3S28P along with the occurrence of chromatin condensation
      in response to DNA damage in G1 phase strengthens the hypothesis. In addition,
      the alteration in the level of H3S10P shows an inverse correlation with that of
      gammaH2AX in a dose-dependent manner and probably occurs from the same
      mononucleosome. We propose that the drop in the levels of histone H3S10
      phosphorylation is a universal phenomenon in response to DNA damage and is a
      trigger to induce transcription repressive state to facilitate repair. 

PMID- 25847425
TI  - More training and awareness are needed to improve the recognition of
      undernutrition in hospitalised children.
AB  - AIM: Reports suggest that 10% of hospitalised children in Europe are
      undernourished. We investigated whether nutritional screening tools (NST) were
      used in Belgian secondary-level hospitals, examined strategies for detecting
      undernutrition and identified barriers preventing the systematic management of
      undernutrition. METHODS: A nationwide questionnaire-based survey of paediatric
      departments in Belgian secondary-level hospitals was carried out from September
      2013 to February 2014. Respondents were dived into French-speaking (Walloon +
      Brussels) and Dutch-speaking (Flemish) departments. RESULTS: We received replies
      from 71 of the 97 (73.2%) departments. Half of the departments - 39.5% Flemish
      speaking and 71.4% Walloon speaking - carried out nutritional screening.
      Undernutrition was identified by measuring weight and length or height (92.7% of
      cases), clinical appraisal (74.7%), mid-upper arm circumference and/or skin fold
      thickness (19.7%). There was no protocol for undernutrition in many Flemish
      (60.5%)- and Walloon (28.6%)-speaking departments. Reasons given for not
      screening were as follows: lack of training (46.9%), ignorance of NST (42.2%) and
      lack of time (29.7%). CONCLUSION: Half of the paediatric departments in Belgian
      secondary-level hospitals did not carry out nutritional screening, and
      differences in current practices and attitudes may be due to cultural and/or
      educational differences.

PMID- 25847426
TI  - A proposed food breakdown classification system to predict food behavior during
      gastric digestion.
AB  - The pharmaceutical industry has implemented the Biopharmaceutics Classification
      System (BCS), which is used to classify drug products based on their solubility
      and intestinal permeability. The BCS can help predict drug behavior in vivo, the
      rate-limiting mechanism of absorption, and the likelihood of an in vitro-in vivo
      correlation. Based on this analysis, we have proposed a Food Breakdown
      Classification System (FBCS) framework that can be used to classify solid foods
      according to their initial hardness and their rate of softening during
      physiological gastric conditions. The proposed FBCS will allow for prediction of
      food behavior during gastric digestion. The applicability of the FBCS framework
      in differentiating between dissimilar solid foods was demonstrated using four
      example foods: raw carrot, boiled potato, white rice, and brown rice. The initial
      hardness and rate of softening parameter (softening half time) were determined
      for these foods as well as their hypothesized FBCS class. In addition, we have
      provided future suggestions as to the methodological and analytical challenges
      that need to be overcome prior to widespread use and adoption of this
      classification system. The FBCS gives a framework that may be used to classify
      food products based on their material properties and their behavior during in
      vitro gastric digestion, and may also be used to predict in vivo food behavior.
      As consumer demand increases for functional and "pharma" food products, the food
      industry will need widespread testing of food products for their structural and
      functional performance during digestion. 

PMID- 25847427
TI  - Qualitative research and its methods in epilepsy: Contributing to an
      understanding of patients' lived experiences of the disease.
AB  - This review paper makes the case for the usefulness of qualitative research
      methods in the context of epilepsy research. It begins with an assessment of the
      current state of epilepsy literature and identifies gaps especially in the
      following: research in 'developing' countries and research around surgery for
      adults with epilepsy. It makes the case that disclosure of people's behaviors,
      actions, and reactions in different, often complex health-care situations can
      indicate how they bring meaning to their disease experiences and support needs.
      It shows the value of encouraging work that clarifies how patients manage their
      illness and how they understand changes in their health and well-being over the
      life course of their illness and how health-care professionals and other
      stakeholder groups care for those with epilepsy. The paper suggests a range of
      methods for addressing gaps in the literature and highlights a range of data
      collection, data analysis, and data interpretation and synthesis techniques that
      are appropriate in this context. It pays particular attention to the strengths of
      qualitative applications in mixed-methods research using an example from a recent
      ulcerative colitis drug trial that indicates how they can be integrated into
      study findings, add rich description, and enhance study outcomes. Ethnographic
      methodology is also presented, as a way of offering rare access to the 'lived
      experience' dimension, before the paper concludes with an assessment of the
      qualitative criteria of credibility, dependability, transferability, and
      confirmability for judging a study's 'trustworthiness'. The criteria evidence not
      only the trustworthiness of data and findings but also the ways in which a study
      has approached any challenges inherent in its research design. 

PMID- 25847428
TI  - People with epilepsy lack knowledge about their disease.
AB  - For people with epilepsy, knowledge of their disease is an important factor in
      optimizing the control of their seizures. Better-informed patients can more
      easily participate in the treatment process, reducing disease-related anxiety and
      coping better with stigma. This study was developed in a Lithuanian tertiary
      epilepsy center to assess knowledge of disease among people with epilepsy, to
      estimate differences in disease knowledge between patient groups, and to evaluate
      how epilepsy influences patients' daily lives. We asked patients to complete a
      questionnaire and collected information from outpatient cards on epilepsy
      etiology, type of seizures, findings of diagnostic tests, and information about
      patients' antiepileptic drugs. Our results showed that people with epilepsy have
      poor knowledge about their disease: almost half of the patients did not identify
      the cause of their illness or their type of seizures; most did not know the
      results of their EEG and neuroimaging studies. Patients also lacked general
      knowledge about their disease and implications for lifestyle. However, cognitive
      deficits were not assessed in this study, and this may have affected the answers
      where patients were required to recall and name their drugs or the dosage of
      medication. Almost half of them believed that epilepsy had changed their lives
      significantly and reported anxiety and constant fear of seizures. Patients were
      also afraid to have because of the possibility they would also have epilepsy.
      There is clearly a great need for improved educational intervention for people
      with epilepsy. 

PMID- 25847429
TI  - Gender differences in social support in persons with epilepsy.
AB  - The present study focused on social support as a key feature of the enhancement
      and maintenance of mental health. So far, literature on gender differences in
      social support and its effects on the experience of stress in individuals with
      epilepsy is scarce. We hypothesized that in individuals with epilepsy, social
      support buffers detrimental effects of stressors (e.g., unpredictable occurrence
      of seizures) on mental health. Additionally, we explored the role of gender in
      this process. In 299 individuals with epilepsy, data from validated
      questionnaires on seizures in the last 3months, perceived support, social network
      size, and depressive symptoms were analyzed. Women reported higher depressive
      symptoms (t=2.51, p<.01) and higher perceived support (t=2.50, p<.01) than men.
      Women and men did not differ in social network size (t=-0.46, p=64), nor in
      experiencing seizures (chi(2)=0.07, p=.82). Regression analyses revealed no
      buffer effects. Perceived support was negatively associated with depressive
      symptoms (B=-0.49, p<.001, 95% CI [-0.67; -0.32]). With regard to depressive
      symptoms, social integration was slightly more beneficial for women (Bcond.=
      0.06, p<.001; 95% CI [-0.09; -0.03]) than for men (Bcond.=-0.02, p=.09; 95% CI [
      0.04; 0.01]). Findings present perceived support and social integration as
      general health resources in individuals with epilepsy regardless of previously
      experienced seizures. They also encourage further research on gender-specific
      effects in individuals with epilepsy and move towards recommendations for
      practitioners and gender-specific interventions. Future aims will be to enhance
      social integration in order to support adjustment to the chronic condition of
      epilepsy and to improve individuals' confidence in support interactions. 

PMID- 25847430
TI  - Psychosocial factors associated with medication adherence in ethnically and
      socioeconomically diverse patients with epilepsy.
AB  - The current study examined psychosocial correlates of medication adherence in a
      socioeconomically and racially diverse sample of patients with epilepsy. Fifty
      five patients with epilepsy completed standardized self-report questionnaires
      measuring depression, stress, social support, and medication and illness beliefs.
      Antiepileptic drug (AED) adherence was measured using the 8-item Morisky
      Medication Adherence Scale 36% reported poor adherence. We tested which
      psychosocial factors were independently and most strongly associated with AED
      adherence. Stress and depression were negatively correlated with adherence, while
      perceived social support was positively correlated with adherence (Ps<.05). When
      all three of these variables and relevant covariates in a multiple regression
      model were included, only perceived social support remained a significant
      predictor of adherence (P=.015). This study is one of the first to suggest the
      importance of targeting social support in screening and intervention approaches
      in order to improve AED adherence among low-income, racially/ethnically diverse
      patients with epilepsy. 

PMID- 25847431
TI  - Interictal epileptiform activity and autism.
AB  - Many individuals with autism have epileptiform discharges on their EEG without
      having definite clinical seizures. The clinical significance of epileptiform
      activity in patients with autism is controversial. Some consider it an
      epiphenomenon of the underlying condition that should be ignored, and others
      believe that frequent spikes may contribute to the cognitive impairment and
      advocate treatment. Several studies have reported variable rates of epileptiform
      activity and variable response to treatment. There is an urgent need to conduct
      controlled clinical trials to assess the true incidence of epileptiform activity
      in children with autism, develop a risk assessment model, and study the
      effectiveness of treatment. This article is part of a Special Issue entitled
      "Autism and Epilepsy". 

PMID- 25847432
TI  - Ductal metaplasia in oesophageal submucosal glands is associated with
      inflammation and oesophageal adenocarcinoma.
AB  - AIMS: Recent studies have suggested that oesophageal submucosal gland (ESMG)
      ducts harbour progenitor cells that may contribute to oesophageal metaplasia. Our
      objective was to determine whether histological differences exist between the
      ESMGs of individuals with and without oesophageal adenocarcinoma (EAC). METHODS
      AND RESULTS: We performed histological assessment of 343 unique ESMGs from 30
      control patients, 24 patients with treatment-naive high-grade columnar dysplasia
      (HGD) or EAC, and 23 non-EAC oesophagectomy cases. A gastrointestinal pathologist
      assessed haematoxylin and eosin-stained ESMG images by using a scoring system
      that assigns individual ESMG acini to five histological types (mucous, serous,
      oncocytic, dilated, or ductal metaplastic). In our model, ductal metaplastic
      acini were more common in patients with HGD/EAC (12.7%) than in controls (3.5%)
      (P = 0.006). We also identified greater proportions of acini with dilation
      (21.9%, P < 0.001) and, to a lesser extent, ductal metaplasia (4.3%, P = 0.001)
      in non-EAC oesophagectomy cases than in controls. Ductal metaplasia tended to
      occur in areas of mucosal ulceration or tumour. CONCLUSIONS: We found a clear
      association between ductal metaplastic ESMG acini and HGD/EAC. Non-EAC cases had
      dilated acini and some ductal dilation. Because ESMGs and ducts harbour putative
      progenitor cells, these associations could have significance for understanding
      the pathogenesis of EAC.

PMID- 25847433
TI  - Preventing occupational stress in healthcare workers.
AB  - BACKGROUND: Healthcare workers can suffer from occupational stress as a result of
      lack of skills, organisational factors, and low social support at work. This may
      lead to distress, burnout and psychosomatic problems, and deterioration in
      quality of life and service provision. OBJECTIVES: To evaluate the effectiveness
      of work- and person-directed interventions compared to no intervention or
      alternative interventions in preventing stress at work in healthcare workers.
      SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials
      (CENTRAL), MEDLINE, EMBASE, PsycINFO, CINAHL, NIOSHTIC-2 and Web of Science up to
      November 2013. SELECTION CRITERIA: Randomised controlled trials (RCTs) of
      interventions aimed at preventing psychological stress in healthcare workers. For
      organisational interventions, interrupted time-series and controlled before-and
      after (CBA) studies were also eligible. DATA COLLECTION AND ANALYSIS: Two review
      authors independently extracted data and assessed trial quality. We used
      Standardised Mean Differences (SMDs) where authors of trials used different
      scales to measure stress or burnout. We combined studies that were similar in
      meta-analyses. We used the GRADE system to rate the quality of the evidence. MAIN
      RESULTS: In this update, we added 39 studies, making a total of 58 studies (54
      RCTs and four CBA studies), with 7188 participants. We categorised interventions
      as cognitive-behavioural training (CBT) (n = 14), mental and physical relaxation
      (n = 21), combined CBT and relaxation (n = 6) and organisational interventions (n
      = 20). Follow-up was less than one month in 24 studies, one to six in 22 studies
      and more than six months in 12 studies. We categorised outcomes as stress,
      anxiety or general health.There was low-quality evidence that CBT with or without
      relaxation was no more effective in reducing stress symptoms than no intervention
      at one month follow-up in six studies (SMD -0.27 (95% Confidence Interval (CI) 
      0.66 to 0.13; 332 participants). But at one to six months follow-up in seven
      studies (SMD -0.38, 95% CI -0.59 to -0.16; 549 participants, 13% relative risk
      reduction), and at more than six months follow-up in two studies (SMD -1.04, 95%
      CI -1.37 to -0.70; 157 participants) CBT with or without relaxation reduced
      stress more than no intervention.CBT interventions did not lead to a considerably
      greater effect than an alternative intervention, in three studies.Physical
      relaxation (e.g. massage) was more effective in reducing stress than no
      intervention at one month follow-up in four studies (SMD -0.48, 95% CI -0.89 to 
      0.08; 97 participants) and at one to six months follow-up in six studies (SMD 
      0.47; 95% CI -0.70 to -0.24; 316 participants). Two studies did not find a
      considerable difference in stress between massage and taking extra breaks.Mental
      relaxation (e.g. meditation) led to similar stress symptom levels as no
      intervention at one to six months follow-up in six studies (SMD -0.50, 95% CI 
      1.15 to 0.15; 205 participants) but to less stress in one study at more than six
      months follow-up. One study showed that mental relaxation reduced stress more
      effectively than attending a course on theory analysis and another that it was
      more effective than just relaxing in a chair.Organisational interventions
      consisted of changes in working conditions, organising support, changing care,
      increasing communication skills and changing work schedules. Changing work
      schedules (from continuous to having weekend breaks and from a four-week to a two
      week schedule) reduced stress with SMD -0.55 (95% CI -0.84 to -0.25; 2 trials,
      180 participants). Other organisational interventions were not more effective
      than no intervention or an alternative intervention.We graded the quality of the
      evidence for all but one comparison as low. For CBT this was due to the
      possibility of publication bias, and for the other comparisons to a lack of
      precision and risk of bias. Only for relaxation versus no intervention was the
      evidence of moderate quality. AUTHORS' CONCLUSIONS: There is low-quality evidence
      that CBT and mental and physical relaxation reduce stress more than no
      intervention but not more than alternative interventions. There is also low
      quality evidence that changing work schedules may lead to a reduction of stress.
      Other organisational interventions have no effect on stress levels. More
      randomised controlled trials are needed with at least 120 participants that
      compare the intervention to a placebo-like intervention. Organisational
      interventions need better focus on reduction of specific stressors.

PMID- 25847435
TI  - Editorial: Sustainable production of renewable energy from non-food crops.
AB  - Since the world faced the petroleum crisis in the 1970s and people started to
      realize the limitation of fossil energy resources coupled with concerns over the
      effects of increasing carbon dioxide in the atmosphere, major efforts were
      devoted to the search for alternative energy sources. 

PMID- 25847436
TI  - More than one way to skin a cat: in-situ engineering of an antibody through photo
      conjugated C2 domain.

PMID- 25847438
TI  - Gender profiling: a gendered race perspective on person-position fit.
AB  - The current research integrates perspectives on gendered race and person-position
      fit to introduce the concept of a gender profile. We propose that both the
      "gender" of a person's biological sex and the "gender" of a person's race (Asians
      are perceived as feminine and Blacks as masculine) help comprise an individual's
      gender profile-the overall femininity or masculinity associated with their
      demographic characteristics. We also propose that occupational positions have
      gender profiles. Finally, we argue that the overall gender profile of one's
      demographics, rather than just one's biological sex, determines one's fit and
      hirability for feminine or masculine occupational roles. The current five studies
      establish the gender profiles of different races and sexes, and then demonstrate
      that individuals with feminine-typed and masculine-typed gender profiles are
      selected for feminine and masculine positions, respectively. These studies
      provide new insights on who gets ahead in different environments. 

PMID- 25847439
TI  - Characterization and risk assessment of polychlorinated biphenyls in soils and
      rice tissues in a suburban paddy field of the Pearl River Delta, South China.
AB  - We investigated the concentration and composition of polychlorinated biphenyls
      (PCBs) in paddy soils and rice tissues and the associated potential health risks
      in the urban agricultural areas of the Pearl River Delta (PRD), South China. The
      results indicated that highly chlorinated PCBs were more prominent in soil when
      the concentrations of low-molecular-weight PCBs were relatively high in rice
      plants. There was a trend of decreasing PCB concentrations with soil depth and a
      significant correlation between PCBs and the total organic carbon or total
      nitrogen concentration in section soils. The PCB concentrations followed the
      order of root > leaf > stem > grain. Although the dioxin toxicity equivalency
      values and estimated daily intake levels (based direct and indirect consumption)
      were lower than in other seriously contaminated regions, there is still a need to
      monitor PCB pollution in urban agriculture because of the PCB emissions from
      capacitor storage following the rapid urbanization experienced in the PRD. 

PMID- 25847440
TI  - Effect of physical sediments reworking on hydrocarbon degradation and bacterial
      community structure in marine coastal sediments.
AB  - The present study aimed to examine whether the physical reworking of sediments by
      harrowing would be suitable for favouring the hydrocarbon degradation in coastal
      marine sediments. Mudflat sediments were maintained in mesocosms under conditions
      as closer as possible to those prevailing in natural environments with tidal
      cycles. Sediments were contaminated with Ural blend crude oil, and in half of
      them, harrowing treatment was applied in order to mimic physical reworking of
      surface sediments. Hydrocarbon distribution within the sediment and its removal
      was followed during 286 days. The harrowing treatment allowed hydrocarbon
      compounds to penetrate the first 6 cm of the sediments, and biodegradation
      indexes (such as n-C18/phytane) indicated that biodegradation started 90 days
      before that observed in untreated control mesocosms. However, the harrowing
      treatment had a severe impact on benthic organisms reducing drastically the
      macrofaunal abundance and diversity. In the harrowing-treated mesocosms, the
      bacterial abundance, determined by 16S rRNA gene Q-PCR, was slightly increased;
      and terminal restriction fragment length polymorphism (T-RFLP) analyses of 16S
      rRNA genes showed distinct and specific bacterial community structure. Co
      occurrence network and canonical correspondence analyses (CCA) based on T-RFLP
      data indicated the main correlations between bacterial operational taxonomic
      units (OTUs) as well as the associations between OTUs and hydrocarbon compound
      contents further supported by clustered correlation (ClusCor) analysis. The
      analyses highlighted the OTUs constituting the network structural bases involved
      in hydrocarbon degradation. Negative correlations indicated the possible shifts
      in bacterial communities that occurred during the ecological succession.

PMID- 25847441
TI  - In search for a compromise between biodiversity conservation and human health
      protection in restoration of fly ash deposits: effect of anti-dust treatments on
      five groups of arthropods.
AB  - Recently, fly ash deposits have been revealed as a secondary refuge of critically
      endangered arthropods specialised on aeolian sands in Central Europe.
      Simultaneously, these anthropogenic habitats are well known for their negative
      impact on human health and the surrounding environment. The overwhelming majority
      of these risks are caused by wind erosion, the substantial decreasing of which is
      thus necessary. But, any effects of anti-dust treatments on endangered arthropods
      have never been studied. We surveyed communities of five arthropod groups (wild
      bees and wasps, leafhoppers, spiders, hoverflies and orthopteroid insects)
      colonising three fly ash deposits in the western Czech Republic. We focused on
      two different anti-dust treatments (~70 and 100 % cover of fly ash by barren
      soil) and their comparison with a control of bare fly ash. Altogether, we
      recorded 495 species, including 132 nationally threatened species (eight of them
      were considered to be extinct in the country) and/or 30 species strictly
      specialised to drift sands. Bees and wasps and leafhoppers contained the
      overwhelming majority of species of the highest conservation interest; a few
      other important records were also in spiders and orthopteroids. Total soil cover
      depleted the unique environment of fly ash and thus destroyed the high
      conservation potential of the deposits. On the other hand, partial coverage (with
      ~30 % of bare fly ash) still offered habitats for many of the most threatened
      species, as we showed by both regression and multivariate analyses, with a
      decrease of wind erosion. This topic still needs much more research interest, but
      we consider mosaic-like preservation of smaller spots of fly ash as one of the
      possible compromises between biodiversity and human health. 

PMID- 25847442
TI  - Sediment properties and trace metal pollution assessment in surface sediments of
      the Laizhou Bay, China.
AB  - Spatial distribution, ecological risk, pollutant source, and transportation of
      trace metals in surface sediments, as well as the sediment properties, were
      analyzed in this study to assess the pollution status of trace metal in the
      Laizhou Bay, China. Results of provenance analyses indicate that surface
      sediments were primarily from weathering products carried by the surrounding
      short rivers and partially from loess matters carried by the Yellow River.
      Variations of trace metal concentrations were mostly controlled by the
      accumulation of weathering products, organic matters, and the hydrodynamics.
      Geoaccumulation index suggests that no Cr pollution occurred in the study area,
      and Cu, Pb, and Zn pollutions appeared only at a few stations. Comparatively, Cd
      and As pollutions were at noticeably weak to moderate level at many stations. The
      combination of six trace metals in this study had a 21% probability of being
      toxic in our study area based on sediment quality guidelines. Enrichment factors
      (EFs) and statistical analyses indicate that Cu, Pb, and Zn were primarily
      derived from the natural process of weathering. By contrast, Cd, As, and Cr
      (especially Cd and As) were provided by the anthropogenic activities to a large
      extent. Due to the dilution of coarse-grained sediments, there was even no
      contamination at some of stations that were obviously influenced by humans. Based
      on the current study of transportation process of fine-grained sediments in
      combination with the spatial distribution of EFs, it is found that the migration
      of anthropogenic trace metals was mainly controlled by the tide in the Laizhou
      Bay. The study suggests that an effective strategies and remedial measures should
      be designed and undertaken to prevent further anthropogenic Cd and As pollutions
      in this area in the future.

PMID- 25847443
TI  - Selective oxidative degradation of toluene for the recovery of surfactant by an
      electro/Fe2+/persulfate process.
AB  - An electro/Fe(2+)/persulfate process has been conducted for toluene removal from
      surfactant (SDS) flushing solution, and the pseudo-second-order reaction rate
      constant (k2 value) of toluene removal has been optimized by a response surface
      methodology (RSM). The results indicated that in this process, the reaction
      between persulfate and externally added Fe(2+) generates sulfate-free radicals,
      and at the same time, Fe(2+) is electro-regenerated at the cathode by the
      reduction of Fe(3+). RSM based on Box-Behnken design (BBD) has been applied to
      analyze the experimental variables, of which the concentrations of persulfate and
      Fe(2+) showed a positive effect on the rate constant of toluene removal, whereas
      the concentration of SDS showed a negative effect. The interactions between pairs
      of variables proved to be significant, such as between SDS, persulfate, and
      Fe(2+) concentrations. ANOVA results confirmed that the proposed models were
      accurate and reliable for analysis of the variables of the
      electro/Fe(2+)/persulfate process. The shapes of the 3D response surfaces and
      contour plots showed that the SDS, persulfate, and Fe(2+) concentrations
      substantially affected the k2 value of toluene removal. The results indicated
      that increasing persulfate or Fe(2+) concentration increased the k2 value,
      whereas increasing SDS concentration decreased the k2 value. The reaction
      intermediates have been identified by GC-MS, and a plausible degradation pathway
      for toluene degradation is proposed.

PMID- 25847444
TI  - Changes in soil microbial functional diversity and biochemical characteristics of
      tree peony with amendment of sewage sludge compost.
AB  - A greenhouse experiment was conducted to investigate the impact of sewage sludge
      compost application on functional diversity of soil microbial communities, based
      on carbon source utilization, and biochemical characteristics of tree peony
      (Paeonia suffruticosa). Functional diversity was estimated with incubations in
      Biolog EcoPlates and well color development was used as the functional trait for
      carbon source utilization. The average well color development and Shannon index
      based on the carbon source utilization pattern in Biolog EcoPlates significantly
      increased with the increasing sludge compost application in the range of 0-45%,
      with a decreasing trend above 45%. Principal component analysis of carbon source
      utilization pattern showed that sludge compost application stimulated the
      utilization rate of D-cellobiose and alpha-D-lactose, while the utilization rate
      of beta-methyl-D-glucoside, L-asparagine, L-serine, alpha-cyclodextrin, gamma
      hydroxybutyric acid, and itaconic acid gradually increased up to a sludge compost
      amendment dosage of 45% and then decreased above 45%. The chlorophyll content,
      antioxidase (superoxide dismutase, catalase, and peroxidase) activities, plant
      height, flower diameter, and flower numbers per plant of tree peony increased
      significantly with sludge compost dosage, reaching a peak value at 45 %, and then
      decreased with the exception that activity of superoxide dismutase and catalase
      did not vary significantly.

PMID- 25847445
TI  - Efficient secretory production of CotA-laccase and its application in the
      decolorization and detoxification of industrial textile wastewater.
AB  - Fungal laccases are typically unstable at high pH and temperature conditions,
      which limit their application in the decolorization of textile wastewater. By
      contrast, the highly stable bacterial laccases can function within a wider pH
      range and at high temperatures, thus have significant potential in treatment for
      textile wastewater. In our previous work, a thermo-alkali-stable CotA-laccase
      gene was cloned from Bacillus pumilus W3 and overexpressed in Escherichia coli.
      In this study, the robust CotA-laccase achieved efficient secretory expression in
      Bacillus subtilis WB600 by screening a suitable signal peptide. A maximum CotA
      laccase yield of 373.1 U/mL was obtained at optimum culture conditions in a 3-L
      fermentor. Furthermore, the decolorization and detoxification of textile industry
      effluent by the purified recombinant CotA-laccase in the presence and absence of
      redox mediators were investigated. Among the potential mediators that enhanced
      effluent decolorization, acetosyringone (ACS) was the most effective. The
      toxicity of the CotA-laccase-ACS-treated effluent was greatly reduced compared
      with that of the crude effluent. To the best of our knowledge, this study is the
      first to report on the heterologous expression of CotA-laccase in B. subtilis.
      The recombinant strain B. subtilis WB600-5 has a great potential in the
      industrial production of this bacterial enzyme, and the CotA-laccase-ACS system
      is a promising candidate for the biological treatment of industrial textile
      effluents.

PMID- 25847446
TI  - Erratum to: Innovative two-stage mesophilic/thermophilic anaerobic degradation of
      sonicated sludge: performances and energy balance.

PMID- 25847447
TI  - Catalytic asymmetric total synthesis of (-)-galanthamine and (-)-lycoramine.
AB  - The catalytic asymmetric total syntheses of (-)-galanthamine (1) and (-)
      lycoramine (2) have been achieved by using a conceptually new strategy featuring
      two metal-catalyzed reactions as the key steps. A new method for the construction
      of 3,4-fused benzofurans has been developed through a palladium-catalyzed
      intramolecular Larock annulation reaction, which was successfully applied to the
      construction of the ABD tricyclic skeleton of 1 and 2. To achieve the asymmetric
      synthesis of 1 and 2, a Sc(III)/N,N'-dioxide complex was used to catalyze the
      enantioselective conjugate addition of 3-alkyl-substituted benzofuranone to
      methyl vinyl ketone for the construction of a chiral quaternary carbon center.

PMID- 25847448
TI  - IL-1beta inhibits ILC3 while favoring NK-cell maturation of umbilical cord blood
      CD34(+) precursors.
AB  - NK cells are innate lymphocytes characterized by the expression of nuclear factor
      interleukin 3 regulated (NFIL3 or E4BP4), eomesodermin (EOMES) transcription
      factors (TFs), and by the ability to exert cytolytic activity and release IFN
      gamma. In the haploidentical-hematopoietic stem cell transplantation (haplo-HSCT)
      setting, CD34(+) donor derived NK cells play a major role in the control of
      leukemic relapses. Therefore, it is important to better define cytokines that
      influence NK-cell differentiation from CD34(+) precursors. We analyzed the
      effects of IL-1beta on NK-cell differentiation from umbilical cord blood (UCB)
      CD34(+) cells. While IL-1beta inhibited CD161(+) CD56(+) cell proliferation, an
      increased expression of LFA-1, CD94/NKG2A, KIRs, and perforin on CD56(+) cells
      was detected. In addition, within the CD161(+) CD56(+) IL-1RI(+) LFA-1(-) cell
      fraction (representing group 3 innate lymphoid cells, ILC3-like cells), a
      significant increase of EOMES, NKp46, and CD94/NKG2A receptors, cytolytic
      granules, and IFN-gamma was detected. This increase was paralleled by a decrease
      of related orphan receptors (RORgammat) TF, NKp44 expression, and IL-22
      production. These data suggest that IL-1beta inhibits ILC3- while favoring NK
      cell maturation. Since in haplo-HSCT conditioning regimen, infections or residual
      leukemia cells may induce IL-1beta production, this may influence the NK/ILC3
      development from donor-derived CD34(+) precursors.

PMID- 25847450
TI  - Immune responses of wild birds to emerging infectious diseases.
AB  - Over the past several decades, outbreaks of emerging infectious diseases (EIDs)
      in wild birds have attracted worldwide media attention, either because of their
      extreme virulence or because of alarming spillovers into agricultural animals or
      humans. The pathogens involved have been found to infect a variety of bird hosts
      ranging from relatively few species (e.g. Trichomonas gallinae) to hundreds of
      species (e.g. West Nile Virus). Here we review and contrast the immune responses
      that wild birds are able to mount against these novel pathogens. We discuss the
      extent to which these responses are associated with reduced clinical symptoms,
      pathogen load and mortality, or conversely, how they can be linked to worsened
      pathology and reduced survival. We then investigate how immune responses to EIDs
      can evolve over time in response to pathogen-driven selection using the
      illustrative case study of the epizootic outbreak of Mycoplasma gallisepticum in
      wild North American house finches (Haemorhous mexicanus). We highlight the need
      for future work to take advantage of the substantial inter- and intraspecific
      variation in disease progression and outcome following infections with EID to
      elucidate the extent to which immune responses confer increased resistance
      through pathogen clearance or may instead heighten pathogenesis. 

PMID- 25847449
TI  - Combination of 12-O-tetradecanoylphorbol-13-acetate with diethyldithiocarbamate
      markedly inhibits pancreatic cancer cell growth in 3D culture and in
      immunodeficient mice.
AB  - The aim of the present study was to determine the effects of 12-O
      tetradecanoylphorbol-13-acetate (TPA) and diethyldithiocarbamate (DDTC) alone or
      in combination on human pancreatic cancer cells cultured in vitro and grown as
      xenograft tumors in nude mice. Pancreatic cancer cells were treated with either
      DDTC or TPA alone, or in combination and the number of viable cells was then
      determined by trypan blue ecxlusion assay and the number of apoptotic cells was
      determined by morphological assessment by staining the cells with propidium
      idiode and examining them under a fluorescence microscope. Treatment with DDTC or
      TPA alone inhibited the growth and promoted the apoptosis of pancreatic cancer
      cells in a concentration-dependent manner. These effects were more prominent
      following treatment with TPA in combination with DDTC than following treatment
      with either agent alone in PANC-1 cells in monolayer cultures and in 3
      dimensional (3D) cultures. The potent effects of the combination treatment on
      PANC-1 cells were associated with the inhibition of nuclear factor-kappaB (NF
      kappaB) activation and the decreased expression of Bcl-2 induced by DDTC, as
      shown by NF-kappaB-dependent reporter gene expression assay and western blot
      analysis. Furthermore, treatment of nude mice with DDTC + TPA strongly inhibited
      the growth of PANC-1 xenograft tumors. The results of the present study indicate
      that the administration of TPA and DDTC in combination may be an effective
      strategy for inhibiting the growth of pancreatic cancer.

PMID- 25847451
TI  - Comparison of mouse plasma and brain tissue homogenate sample pretreatment
      methods prior to high-performance liquid chromatography for a new 1,2,4-triazole
      derivative with anticonvulsant activity.
AB  - The focus of the study was to develop a bio-analytical assay for a 1,2,4-triazole
      derivative from plasma and brain tissue homogenate samples. The goal was to
      compare analytical techniques that facilitate high accuracy with simplified
      sample processing. In this study, commonly used standard protein precipitation
      and solid-phase extraction methods utilizing C18 and cartridges of Hybrid
      technology were compared in terms of their ability for sample pretreatment and
      removal of biological matrices before high-performance liquid chromatography
      quantification. Fast classical reversed-phase chromatography on a C18 column
      paired with selective sample preparation using Hybrid solid-phase extraction
      technology resulted in the most precise bio-analytical determination of the
      hydrophobic 1,2,4-triazole derivative in both biological samples studied. The
      obtained recovery values were above 95% with the coefficient of variation lower
      than 5%. 

PMID- 25847452
TI  - Is drug-eluting-bead transcatheter arterial chemoembolization (TACE) associated
      with better tumor response than conventional TACE in a meta-analysis?: Authors'
      reply.

PMID- 25847453
TI  - Undecametallic and hexadecametallic ferric oxo-hydroxo/ethoxo pivalate clusters.
AB  - Synthesis strategies for highly condensed {Fe11} and {Fe16} pivalate clusters
      have been developed based on archetypal geometrically frustrated triangular
      {Fe3(MU3-O)} motifs that are interlinked via oxo, hydroxo, ethoxo, and
      carboxylate groups. 

PMID- 25847454
TI  - Reticulate evolution and sea-level fluctuations together drove species
      diversification of slipper orchids (Paphiopedilum) in South-East Asia.
AB  - South-East Asia covers four of the world's biodiversity hotspots, showing high
      species diversity and endemism. Owing to the successive expansion and contraction
      of distribution and the fragmentation by geographical barriers, the tropical
      flora greatly diversified in this region during the Tertiary, but the
      evolutionary tempo and mode of species diversity remain poorly investigated.
      Paphiopedilum, the largest genus of slipper orchids comprising nearly 100
      species, is mainly distributed in South-East Asia, providing an ideal system for
      exploring how plant species diversity was shaped in this region. Here, we
      investigated the evolutionary history of this genus with eight cpDNA regions and
      four low-copy nuclear genes. Discordance between gene trees and network analysis
      indicates that reticulate evolution occurred in the genus. Ancestral area
      reconstruction suggests that vicariance and long-distance dispersal together led
      to its current distribution. Diversification rate variation was detected and
      strongly correlated with the species diversity in subg. Paphiopedilum (~80
      species). The shift of speciation rate in subg. Paphiopedilum was coincident with
      sea-level fluctuations in the late Cenozoic, which could have provided ecological
      opportunities for speciation and created bridges or barriers for gene flow.
      Moreover, some other factors (e.g. sympatric distribution, incomplete
      reproductive barriers and clonal propagation) might also be advantageous for the
      formation and reproduction of hybrid species. In conclusion, our study suggests
      that the interplay of reticulate evolution and sea-level fluctuations has
      promoted the diversification of the genus Paphiopedilum and sheds light into the
      evolution of Orchidaceae and the historical processes of plant species
      diversification in South-East Asia. 

PMID- 25847455
TI  - Permeability and shear modulus of articular cartilage in growing mice.
AB  - Articular cartilage maturation is the postnatal development process that adapts
      joint surfaces to their site-specific biomechanical demands. Understanding the
      changes in mechanical tissues properties during growth is a critical step in
      advancing strategies for orthopedics and for cell- and biomaterial- based
      therapies dedicated to cartilage repair. We hypothesize that at the microscale,
      the articular cartilage tissue properties of the mouse (i.e., shear modulus and
      permeability) change with the growth and are dependent on location within the
      joint. We tested cartilage on the medial femoral condyle and lateral femoral
      condyle of seven C57Bl6 mice at different ages (2, 3, 5, 7, 9, 12, and 17 weeks
      old) using a micro-indentation test. Results indicated that permeability
      decreased with age from 2 to 17 weeks. Shear modulus reached a peak at the end of
      the growth (9 weeks). Within an age group, shear modulus was higher in the MFC
      than in the LFC, but permeability did not change. We have developed a method that
      can measure natural alterations in cartilage material properties in a murine
      joint, which will be useful in identifying changes in cartilage mechanics with
      degeneration, pathology, or treatment. 

PMID- 25847456
TI  - Fabrication of drug-loaded anti-infective guided tissue regeneration membrane
      with adjustable biodegradation property.
AB  - For guided tissue regeneration (GTR) membrane, synchronization of the membrane
      biodegradation rate and tissue regeneration rate is important. Besides, the major
      reason for GTR membrane failure in clinical application is infection which can be
      prevented by loading anti-bacterial drug. To realize the consistency in membrane
      degradation rate and tissue regeneration rate of the anti-infective membrane, we
      developed metronidazole-loaded electrospun poly(E-caprolactone)-gelatin nanofiber
      membranes with different poly(E-caprolactone)/gelatin ratios (95:5, 90:10, 80:20,
      70:30, 60:40, and 50:50). Homogeneous nanofibers were successfully fabricated.
      The mechanical strength of the membranes increased with the poly(E-caprolactone)
      content, while the hydrophilicity decreased. The controlled and sustained release
      of metronidazole from all the membranes prevented the colonization of anaerobic
      bacteria. At all poly(E-caprolactone)/gelatin ratios, all the membranes presented
      good biocompatibility while the increase of gelatin content resulted in enhanced
      cell adhesion and proliferation. Subcutaneous implantation in rabbits for 8
      months demonstrated that all the membranes showed good biocompatibility without
      infection. Both in vitro and in vivo results showed that the biodegradation rate
      of the membranes was accelerated with the increase of gelatin content. The
      biodegradation rate and biocompatibility of the membranes can be adjusted by
      changing the PCL/gelatin ratio. The optimal membrane can be chosen based on the
      patient and tissue type to realize the synchronization of membrane degradation
      with tissue regeneration for the best treatment effect. 

PMID- 25847457
TI  - In vitro and in vivo toxicity evaluation of plant virus nanocarriers.
AB  - The use of biological self-assembling materials, plant virus nanoparticles in
      particular, appears very intriguing as it allows a great choice of symmetries and
      dimensions, easy chemical and biological engineering of both surface and/or
      internal cavity as well as safe and rapid production in plants. In this
      perspective, we present an initial evaluation of the safety profile of two
      structurally different plant viruses produced in Nicotiana benthamiana L. plants:
      the filamentous Potato virus X and the icosahedral Tomato bushy stunt virus. In
      vitro haemolysis assay was used to test the cytotoxic effects, which could arise
      by pVNPs interaction with cellular membranes, while early embryo assay was used
      to evaluate toxicity and teratogenicity in vivo. Data indicates that these
      structurally robust particles, still able to infect plants after incubation in
      serum up to 24h, have neither toxic nor teratogenic effects in vitro and in vivo.
      This work represents the first safety-focused characterization of pVNPs in view
      of their possible use as drug delivery carriers. 

PMID- 25847458
TI  - Layer by layer assembled films between hemoglobin and multiwall carbon nanotubes
      for pH-switchable biosensing.
AB  - Although pH-switchable behaviors have been reported based on multilayer films
      modified electrodes, their pH-switchable biosensing is still difficult due to the
      existence of the electroactive mediator. In this study, we report the pH
      dependable determination of hydrogen peroxide (H2O2) based on a four-bilayer film
      fabricated through layer by layer assembly between hemoglobin (Hb) and multiwall
      carbon nanotubes (MWCNTs). We observed that response of electroactive probe
      Fe(CN)6(3-) at the multilayer films was very sensitive and reversible to pH
      values of phosphate buffer solutions phosphate buffer solution with cyclic
      voltammetry. The reduction peak height of Fe(CN)6(3-) at the multilayer film
      could reach ~221MUA at pH 3.0 while 0MUA at pH 9.0. The linear range for the
      detection of H2O2 at pH 3.0 was from 12.5MUM to 10.4mM, which was much wider than
      that at pH 9.0. Our results demonstrated that the detection of H2O2 with the
      proposed modified electrode is dependent on pH values of phosphate buffer
      solution. Moreover, the component of multilayer films has impacts on the
      performance of biosensors with pH-switchable behaviors. 

PMID- 25847459
TI  - Nanostructured sensor based on carbon nanotubes and clavanin A for bacterial
      detection.
AB  - Unusual methods for specific detection of pathogenic bacteria are becoming key
      points for control and identification of problems related to health and
      (bio)safety. In this context, this work aims to propose a new approach for the
      development of nanostructured biosensors based on carbon nanotubes (CNTs) and
      antimicrobial peptides for bacterial detection. Firstly, the antimicrobial
      peptide clavanin A (ClavA) was chemically immobilized on CNTs and surface
      immobilized ClavA was used to detect Klebsiella pneumoniae, Enterococcus
      faecalis, Escherichia coli and Bacillus subtilis in a direct assay format. We
      used electrochemical impedance spectroscopy technique to evaluate the
      effectiveness and sensitivity of the ClavA-based biosensors by measuring the
      modifications in their electrochemical responses before and after incubation in
      presence of different bacteria concentrations. The biosensor was able to
      discriminate between bacteria concentrations in the 10(2)-10(6)CFU mL(-1) range.
      Atomic force microscopy analysis confirmed the biosensor functionality for
      bacterial recognition. This new sensor system was capable of differentiating
      between Gram-positive and Gram-negative bacteria, since ClavA showed different
      affinities toward the pathogenic bacteria species.

PMID- 25847460
TI  - Why searching for psychosis in diverse settings is important for global research
      and mental health systems development.
AB  - BACKGROUND: The INTREPID programme of research aims to establish comparable
      studies of incident psychosis in a number of low- and middle-income countries
      (LMICs). DISCUSSION: The importance of this cannot be under-estimated, as this
      will enable the testing of existing findings and evidence across differing
      environmental contexts; and will permit the identification of new and unique
      evidence that is only apparent within specific contexts. The epidemiological,
      aetiological and phenomenological insights derived from this programme are likely
      to inform major research advances of the next decades. Of equal importance, by
      adopting novel methods for detecting psychosis 'cases' in low-resourced settings,
      the researchers will be able to test two key hypotheses that could revolutionize
      clinical research and service provision within LMIC settings: (1) that informal
      providers can be incorporated successfully into an adequate (and perhaps even
      superior) case-detection system that is community and population-based (rather
      than hospital-based); and (2) that informal providers can be integrated
      meaningfully into the pathway to care (and perhaps even long-term management) of
      patients with incident psychosis living in low-resourced settings.

PMID- 25847461
TI  - Belatacept in recurrent focal segmental glomerulosclerosis after kidney
      transplantation.

PMID- 25847463
TI  - Oral Mucoceles in Children--Analysis of 56 New Cases.
AB  - BACKGROUND: Mucoceles are common cystic lesions of the oral mucosa. Extravasation
      mucoceles (EMs) are mainly found in the lower lip of young patients, whereas
      retention mucoceles (RMs) are usually located in the cheek or palate of older
      patients. This study was undertaken to more fully characterize the
      clinicopathologic features of mucoceles in pediatric patients. METHODS: The
      records of 56 pediatric patients with mucoceles were included in the study. Age,
      sex, history of trauma, intraoral site, size, and method of treatment were
      evaluated. Histopathologically the lesions were classified as being EMs or RMs.
      RESULTS: The age range was 1.5 to 16 years (mean age 11.2 yrs). Of the 56
      patients, 24 (43%) were males and 32 (57%) were females, with a male:female ratio
      of 1:1.33. A history of trauma was recorded in 32 (57%) patients of the lower
      lip. The intraoral sites were the lower lip (38 [68%]), tongue (10 [18%]), and
      floor of the mouth (8 [14%]). Of the 56 patients, 44 (79%) were EM and 12 (21%)
      were ranulas. No RMs were found. Mucoceles ranged from 0.3 to 3.8 cm in diameter
      (mean 0.9 cm). The treatment of EMs was surgical excision. Cryosurgey,
      electrosurgery, and carbon dioxide laser were also used. CONCLUSION: In contrast
      to adults, where EM and RM types can be found, among children all cases are of
      the EM type. The disparate site and age incidences of EMs and RMs of the oral
      mucosa suggest that these two types are not related and possibly have a different
      etiopathogenesis.

PMID- 25847462
TI  - Spinal muscular atrophy associated with progressive myoclonic epilepsy: A rare
      condition caused by mutations in ASAH1.
AB  - OBJECTIVE: To present the clinical features and the results of laboratory
      investigations in three patients with spinal muscular atrophy associated with
      progressive myoclonic epilepsy (SMA-PME), a rare condition caused by mutations in
      the N-acylsphingosine amidohydrosilase 1 (ASAH1) gene. METHODS: The patients were
      submitted to clinical evaluation, neurophysiologic investigations (that included
      wakefulness and sleep electroencephalography [EEG], video-polygraphic recording
      with jerk-locked back-averaging, multimodal evoked potentials, and
      electromyography), brain magnetic resonance imaging (MRI), biochemical screening,
      muscle and skin biopsies, and molecular genetic analysis. RESULTS: The main
      clinical features were onset in childhood with proximal muscular weakness,
      generalized epilepsy with absences and myoclonic seizures, cognitive impairment
      of variable degree; the course was progressive with muscle wasting and
      uncontrolled epileptic seizures. In one patient, earlier onset before the age of
      2 years was associated with a more complex clinical picture, with abnormal eye
      movements, progressive cognitive impairment, and a more rapid and severe course.
      EEG/polygraphic data were consistent with PME, demonstrating generalized spike
      and-wave discharges, evidence of positive and negative myoclonia, and prominent
      photosensitivity. In one patient, transcranial magnetic stimulation showed a
      hyperexcitable motor cortex, whereas somatosensory evoked potentials were
      unaffected. Possible involvement of the central acoustic and visual pathways was
      suggested by abnormal auditory and visual evoked potentials. Muscle biopsies
      showed typical signs of neurogenic damage. Molecular genetic analysis showed
      mutations of the ASAH1 gene. SIGNIFICANCE: Our data indicate that SMA-PME
      associated with ASAH1 mutations is a genetically distinct condition with specific
      clinical and neurophysiologic features. Further studies are warranted to explore
      the role of the ASAH1 gene in muscle and brain function.

PMID- 25847464
TI  - Biogeographic consequences of nutrient enrichment for plant-herbivore
      interactions in coastal wetlands.
AB  - A major challenge in ecology is to understand broadscale trends in the impact of
      environmental change. We provide the first integrative analysis of the effects of
      eutrophication on plants, herbivores, and their interactions in coastal wetlands
      across latitudes. We show that fertilisation strongly increases herbivory in salt
      marshes, but not in mangroves, and that this effect increases with increasing
      latitude in salt marshes. We further show that stronger nutrient effects on plant
      nitrogen concentration at higher latitudes is the mechanism likely underlying
      this pattern. This biogeographic variation in nutrient effects on plant-herbivore
      interactions has consequences for vegetation, with those at higher latitudes
      being more vulnerable to consumer pressure fuelled by eutrophication. Our work
      provides a novel, mechanistic understanding of how eutrophication affects plant
      herbivore systems predictably across broad latitudinal gradients, and highlights
      the power of incorporating biogeography into understanding large-scale
      variability in the impacts of environmental change. 

PMID- 25847465
TI  - Prevalence, demographics, and complications of cleft palate surgery.
AB  - INTRODUCTION: Current published data on the demographics of cleft lip and palate
      is sparse and differs intranationally in reported incidence, demographics, and
      complication rates, making accurate local data both valuable and useful. We
      investigate the prevalence, demographics, and complications of cleft palate
      correction surgery in the inpatient setting over a 15-year period. METHODS: A
      retrospective review of The California Hospital Discharge Data sets of all
      pediatric patients who underwent cleft palate repair or cleft palate revision
      from 1997 to 2011. Children's hospitals (CHs) were analyzed as a separate group.
      For each record, age, gender, ethnicity, length of stay, total charges, principal
      payer, complications, and disposition were analyzed. RESULTS: 10,450 correction
      surgeries were performed during 1997-2011. This was an annual case-volume of 697
      and annual population-adjusted rate of 2.0, neither of which changed over time
      (p=0.9 and 0.06, respectively). Of all surgeries, 21.5% were revisions, 48.3%
      were performed in CHs, 56.2% were performed on males, and 65.5% were performed on
      Caucasians. The median length of stay was 1 day, which did not change over time
      (p=1.0). The median total charges increased from $9.074 to $35,643 over the
      studied period (p<0.001). Admission to CHs was associated with shorter stay (1-3
      days vs. 1-4 days) and higher total charges ($15,560 vs. $13,242; both p<0.001).
      Complications occurred in 393 (3.8%) of the surgeries. This percentage did not
      change over time (p=0.2). The most common complication was
      fistula/abscess/infection, which occurred in 159 cases (1.5%). Respiratory
      complications requiring ventilation occurred 66 cases (0.6%). Complications were
      more common in CHs (4.8% vs. 2.8%; p<0.001). Mortality rate was <0.1%.
      CONCLUSIONS: Our study constitutes the entire surgical cohort within a state,
      allowing for an accurate representation of the true perioperative complication
      rate of these procedures. The prevalence, demographics, and outcomes of the cleft
      palate correction surgery have remained unchanged during 1997-2011. Collectively,
      our data suggest that primary and secondary palatoplasty present low
      perioperative risk.

PMID- 25847466
TI  - May chronic rhinosinusitis in children be diagnosed by clinical symptoms?
AB  - OBJECTIVES: Chronic rhinosinusitis (CRS) is a common disease in childhood but is
      often underdiagnosed because the symptoms are subtle and similar to other nasal
      pathologies. No clinical symptom is pathognomonic, and consensus documents
      suggest nasal fibroendoscopy (NF) or imaging criteria (computed tomography,
      magnetic resonance imaging) as the gold standards for diagnosis of CRS. However,
      considering the frequent unavailability of such tools to physicians, we designed
      this study to evaluate whether combinations of symptoms may achieve a clinical
      diagnosis of CRS in children as confirmed by NF. METHODS: The study population
      consisted of 275 children with a clinical diagnosis of CRS, in 228 of whom
      diagnosis of CRS was confirmed by NF, while in 47 diagnosis was not confirmed by
      NF and they served as the control group. The symptoms considered were nasal
      obstruction, nasal discharge, cough, facial pain, and halitosis, using for
      statistical analysis multivariate logistic regression, Wald tests, and receiver
      operating characteristic (ROC) curve. RESULTS: The multivariate logistic
      regression for CRS symptoms indicated rhinorrea as the strongest predictor of
      CRS. With three symptoms the probability of CRS was from 60% to 75% without
      rhinorrea and 77-91% in the presence of this symptom, with four symptoms the
      probability was over 93%, and with all the five symptoms the probability of
      having CRS was virtually 100%. CONCLUSIONS: These findings suggest that an
      initial symptoms assessment may help to recognize children with a high
      probability of CRS, thus reducing the need of NF or imaging techniques.

PMID- 25847467
TI  - Antiviral treatment discontinuation among hepatitis C-infected individuals with
      thrombocytopenia.

PMID- 25847468
TI  - Misdiagnosis of patients may be derived from the interfering factors and used cut
      offs in indexes.

PMID- 25847469
TI  - Answer to 'Misdiagnosis of patients may be derived from the interfering factors
      and used cut-offs in indexes'.

PMID- 25847471
TI  - Theodore Lionel Sourkes obituary.

PMID- 25847470
TI  - Synthetic Active Site Model of the [NiFeSe] Hydrogenase.
AB  - A dinuclear synthetic model of the [NiFeSe] hydrogenase active site and a
      structural, spectroscopic and electrochemical analysis of this complex is
      reported. [NiFe('S2Se2')(CO)3] (H2'S2Se2' = 1,2-bis(2-thiabutyl-3,3-dimethyl-4
      selenol)benzene) has been synthesized by reacting the nickel selenolate complex
      [Ni('S2Se2')] with [Fe(CO)3bda] (bda = benzylideneacetone). X-ray crystal
      structure analysis confirms that [NiFe('S2Se2')(CO)3] mimics the key structural
      features of the enzyme active site, including a doubly bridged heterobimetallic
      nickel and iron center with a selenolate terminally coordinated to the nickel
      center. Comparison of [NiFe('S2Se2')(CO)3] with the previously reported thiolate
      analogue [NiFe('S4')(CO)3] (H2'S4' = H2xbsms = 1,2-bis(4-mercapto-3,3-dimethyl-2
      thiabutyl)benzene) showed that the selenolate groups in [NiFe('S2Se2')(CO)3] give
      lower carbonyl stretching frequencies in the IR spectrum. Electrochemical studies
      of [NiFe('S2Se2')(CO)3] and [NiFe('S4')(CO)3] demonstrated that both complexes do
      not operate as homogenous H2 evolution catalysts, but are precursors to a solid
      deposit on an electrode surface for H2 evolution catalysis in organic and aqueous
      solution.

PMID- 25847472
TI  - Development and validation of a clinical scale for rating the severity of
      blepharospasm.
AB  - Existing scales for rating the severity of blepharospasm (BSP) are limited by a
      number of potential drawbacks. We therefore developed and validated a novel scale
      for rating the severity of BSP. The development of the scale started with careful
      examination of the clinical spectrum of the condition by a panel of experts who
      selected phenomenological aspects thought to be relevant to disease severity.
      Thereafter, selected items were first checked for reliability, then reliable
      items were combined to generate the scale, and clinimetric properties of the
      scale were evaluated. Finally, the confidence with which the scale could be used
      by people without high levels of movement disorders skill was assessed. The new
      scale, based on objective criteria, yielded moderate to almost perfect
      reliability, acceptable internal consistency, satisfactory scaling assumptions,
      lack of floor and ceiling effects, partial correlations with a prior severity
      scale and with a quality of life scale, and good sensitivity to change. Despite a
      few limitations, the foregoing features make the novel scale more suitable than
      existing scales to assess the severity of BSP in natural history and
      pathophysiologic studies as well as in clinical trials.

PMID- 25847473
TI  - Anti-influenza virus effects of cocoa.
AB  - BACKGROUND: Cocoa contains biologically active ingredients that have broad
      spectrum antimicrobial activity, which includes an inhibitory effect on influenza
      virus infection. RESULTS: A cocoa extract (CE) was prepared by treating defatted
      cocoa powder with boiling water. The extract demonstrated dose-dependent
      inhibition of infection in Madin-Darby canine kidney (MDCK) cells infected with
      human influenza virus A (H1N1, H3N2), human influenza virus B and avian influenza
      viruses (H5N1, H5N9). CE inhibited viral adsorption to MDCK cells. Animal
      experiments showed that CE significantly improved survival in mice after intra
      nasal administration of a lethal dose of influenza virus. In human intervention
      trials, participants were allocated to two groups, one in which the participants
      ingested cocoa for 3 weeks before and after vaccination against A(H1N1)pdm2009
      influenza virus and another in which the participants did not ingest cocoa.
      Neutralizing antibody titers against A(H1N1)pdm2009 influenza virus increased
      significantly in both groups; however, the extent of the increase was not
      significantly different between the two groups. Although natural killer cell
      activity was also elevated in both groups, the increase was more substantial in
      the cocoa intake group. CONCLUSION: Drinking cocoa activates natural immunity and
      enhances vaccination-induced immune response, providing stronger protection
      against influenza virus infection and disease onset.

PMID- 25847474
TI  - Higher incidence of esophageal lesions after ablation of atrial fibrillation
      related to the use of esophageal temperature probes.
AB  - BACKGROUND: Endoscopically detected esophageal lesions (EDELs) have been
      identified in apparently asymptomatic patients after catheter ablation of atrial
      fibrillation (AF). The use of esophageal probes to monitor luminal esophageal
      temperature (LET) during catheter ablation to protect esophageal damage is
      currently controversial. OBJECTIVE: The purpose of this study was to investigate
      the impact of the use of esophageal temperature probes during AF catheter
      ablation on the incidence of EDELs. METHODS: Eighty consecutive patients (mean
      age 63.8 +/- 11.36 years; 68.8% men) with symptomatic, drug-refractory paroxysmal
      (n = 52, 65%) or persistent AF who underwent left atrial radiofrequency catheter
      ablation were prospectively enrolled. Posterior wall ablation was power limited
      (<=25 W). In the first 40 patients, LET was monitored continuously (group A),
      whereas no esophageal temperature probe was used in group B (n = 40 patients).
      Assessment of EDEL was performed by endoscopy within 2 days after radiofrequency
      catheter ablation. RESULTS: Overall, 13 patients (16%) developed EDELs after AF
      ablation. The incidence of EDELs was significantly higher in group A than group B
      (30% vs 2.5%, P < .01). Within group A, patients who developed EDEL had higher
      maximal LET during AF ablation than patients without EDEL (40.97 +/- 0.92 degrees
      C vs 40.14 +/- 1.1 degrees C, P = .02). Multivariable logistic regression
      analysis revealed the use of an esophageal temperature probe as the only
      independent predictor for the development of EDEL (odds ratio 16.7, P < .01).
      CONCLUSION: The use of esophageal temperature probes in the setting of AF
      catheter ablation per se appears to be a risk factor for the development of EDEL.

PMID- 25847476
TI  - Differentiating the origin of outflow tract ventricular arrhythmia using a
      simple, novel approach.
AB  - BACKGROUND: Numerous electrocardiographic (ECG) criteria have been proposed to
      identify localization of outflow tract ventricular arrhythmias (OT-VAs); however,
      in some cases, it is difficult to accurately localize the origin of OT-VA using
      the surface ECG. OBJECTIVE: The purpose of this study was to assess a simple
      criterion for localization of OT-VAs during electrophysiology study. METHODS: We
      measured the interval from the onset of the earliest QRS complex of premature
      ventricular contractions (PVCs) to the distal right ventricular apical signal
      (the QRS-RVA interval) in 66 patients (31 men aged 53.3 +/- 14.0 years; right
      ventricular outflow tract [RVOT] origin in 37) referred for ablation of
      symptomatic outflow tract PVCs. We prospectively validated this criterion in 39
      patients (22 men aged 52 +/- 15 years; RVOT origin in 19). RESULTS: Compared with
      patients with RVOT PVCs, the QRS-RVA interval was significantly longer in
      patients with left ventricular outflow tract (LVOT) PVCs (70 +/- 14 vs 33.4+/-10
      ms, P < .001). Receiver operating characteristic analysis showed that a QRS-RVA
      interval >=49 ms had sensitivity, specificity, and positive and negative
      predictive values of 100%, 94.6%, 93.5%, and 100%, respectively, for prediction
      of an LVOT origin. The same analysis in the validation cohort showed sensitivity,
      specificity, and positive and negative predictive values of 94.7%, 95%, 95%, and
      94.7%, respectively. When these data were combined, a QRS-RVA interval >=49 ms
      had sensitivity, specificity, and positive and negative predictive values of 98%,
      94.6%, 94.1%, and 98.1%, respectively, for prediction of an LVOT origin.
      CONCLUSION: A QRS-RVA interval >=49 ms suggests an LVOT origin. The QRS-RVA
      interval is a simple and accurate criterion for differentiating the origin of
      outflow tract arrhythmia during electrophysiology study; however, the accuracy of
      this criterion in identifying OT-VA from the right coronary cusp is limited.

PMID- 25847475
TI  - Complications from prophylactic replacement of cardiac implantable electronic
      device generators in response to United States Food and Drug Administration
      recall: A systematic review and meta-analysis.
AB  - BACKGROUND: The number of cardiac implantable electronic device (CIED) recalls
      and advisories has increased over the past 3 decades, yet no consensus exists on
      how to best manage patients with these CIEDs, partially because rates of
      complications from prophylactic replacement are unknown. OBJECTIVE: The purpose
      of this study was to establish rates of complications when recalled CIED
      generators are replaced prophylactically. METHODS: We searched MEDLINE and the
      Cochrane Controlled Trials Register for reports of prophylactic replacement of
      recalled CIED generators. Studies with <20 subjects were excluded. We then
      conducted a meta-analysis of qualifying studies to determine the rates of
      combined major complications, mortality, and reoperation. RESULTS: We identified
      7 citations that met our inclusion criteria and reported >=1 end-points of
      interest. Four were single center, and 3 were multicenter. Six studies collected
      data retrospectively (n = 1213) and 1 prospectively (n = 222). Using a random
      effects model to combine data from all included studies, the rate of major
      complications was 2.5% (95% confidence interval [CI] 1.0%-4.5%). Combining data
      from 6 studies reporting mortality and reoperation, the rates were 0.5% (95% CI
      0.1%-0.9%) and 2.5% (95% CI 0.8%-4.5%), respectively. CONCLUSION: Prophylactic
      replacement of recalled CIED generators is associated with a low mortality rate
      but nontrivial rates of other major complications similar to those reported when
      CIED generators are replaced for other reasons. Thus, when considering replacing
      a recalled CIED generator, known risks of elective generator replacement likely
      apply and can be weighed against risks associated with device failure.

PMID- 25847477
TI  - Incidence and characteristics of complications in the setting of second
      generation cryoballoon ablation: A large single-center study of 500 consecutive
      patients.
AB  - BACKGROUND: The second-generation cryoballoon Advance (CB-A) recently launched on
      the market has technical modifications designed to significantly improve
      procedural outcome with respect to the first-generation device. OBJECTIVE: The
      purpose of this study was to evaluate the overall incidence of complications in a
      large sample of patients having undergone pulmonary vein (PV) isolation with CB-A
      technology. METHODS: All consecutive patients who underwent PV isolation
      procedures using CB-A technology between June 2012 and February 2015 were
      considered. Exclusion criteria were presence of an intracavitary thrombus,
      uncontrolled heart failure, moderate or severe valvular disease, left atrial
      diameter >=55 mm, and contraindications to general anesthesia. RESULTS: During
      the study period, 500 consecutive patients (67% male, age 57.6 +/- 12.9 years)
      were enrolled. Major complications occurred in 10 patients (2.0%): vascular
      complications at the puncture site in 6 (1.2%), and thromboembolic events,
      cardiac tamponade, persisting phrenic nerve palsy, and retroperitoneal hematoma
      all occurred in a single patient respectively (0.2%). Phrenic nerve palsy
      occurred in 36 patients (7.2%) and did not revert in only 1 patient at final
      follow-up of 20 months. No deaths related to the procedure occurred. No
      predictors of major complication were found. CONCLUSION: The present findings
      highlight that PV isolation using CB-A technology can be safely performed with a
      low incidence of adverse events. The incidence of major complications after
      atrial fibrillation ablation procedures using CB-A technology was 2% in our
      study. The most frequent complication consisted of vascular complications at the
      puncture site. No deaths related to the procedure occurred.

PMID- 25847478
TI  - Amino-terminal B-natriuretic peptide levels and postablation recurrence in
      hypertensive patients with paroxysmal atrial fibrillation.
AB  - BACKGROUND: Amino-terminal B-type natriuretic peptide (NT-proBNP) has been shown
      to predict postablation recurrences of atrial fibrillation (AF); however, given
      the associations of natriuretic peptides with various cardiovascular parameters
      potentially related to AF, whether the observed association with recurrence is
      truly an independent one is not clear. OBJECTIVE: The purpose of this analysis
      was to assess the association of NT-proBNP levels with AF recurrence after
      radiofrequency ablation. METHODS: This was a post hoc analysis of a prospective
      study of 296 hypertensive patients with symptomatic paroxysmal AF and no history
      of heart failure who were scheduled to undergo pulmonary vein isolation. NT
      proBNP was measured at baseline, and patients were followed for a median of 13.7
      months. RESULTS: NT-proBNP levels at baseline were higher in patients with
      recurrence (269 pg/mL [199-361 pg/mL]) vs those who remained arrhythmia-free (188
      pg/mL [146-320 pg/mL], P<.001). In a univariate Cox regression model, each higher
      quartile of NT-proBNP corresponded to a 47% (95% confidence interval 21.5%-77.9%)
      increase in the risk of recurrence. However, when baseline clinical AF burden, in
      terms of the number of clinical AF episodes in the previous year, was added to
      the model, the association of NT-proBNP lost its significance (adjusted hazard
      ratio 1.22, 95% confidence interval 0.94-1.57). CONCLUSION: This is the largest
      series to date showing that NT-proBNP is a univariate predictor of postablation
      AF recurrence. However, it seems that adjustment for other covariates, including
      the number of AF episodes within the previous year, renders this association
      nonsignificant.

PMID- 25847480
TI  - A phase I study of resminostat in Japanese patients with advanced solid tumors.
AB  - PURPOSE: This study was performed to evaluate the safety and determine the
      recommended dose (RD) of resminostat monotherapy, an oral histone deacetylase
      (HDAC) inhibitor, in Japanese patients with advanced solid tumors. METHODS:
      Resminostat was administered to patients with advanced solid tumors on a 14-day
      cycle consisting of once-daily administration on days 1-5. The dose was initiated
      at 400 mg and increased to 600 mg and then 800 mg. Treatment with resminostat was
      continued until disease progression or discontinuation for any other reason. Dose
      limiting toxicities (DLTs) were assessed according to the adverse drug reactions
      occurring in the first cycle. Secondary objectives included the pharmacokinetics,
      pharmacodynamics, and efficacy. RESULTS: A total of 12 patients were enrolled in
      the study and received resminostat. No DLTs were reported in any patient. The
      maximum tolerated dose was not reached. Frequently reported grade 3/4 adverse
      drug reactions were as follows: lymphocytopenia (33.3 %), thrombocytopenia (25.0
      %), neutropenia (16.7 %), and leukocytopenia (16.7 %). Pharmacokinetic analysis
      revealed that there was no accumulation of the drug over the 5-day administration
      period and no significant difference in pharmacokinetic parameters between the
      single dose and multiple doses. Measurement of acetylated H4 histone protein
      levels in peripheral blood mononuclear cells demonstrated that resminostat
      inhibited HDAC activity at all the doses assessed. No patients had a complete or
      partial response, whereas three patients had stable disease. CONCLUSIONS:
      Resminostat was safely administered to Japanese patients with advanced solid
      tumors. The RD of resminostat monotherapy in Japanese patients was estimated to
      be 800 mg.

PMID- 25847479
TI  - Determinants of the activities of antifolates delivered into cells by folate
      receptor-mediated endocytosis.
AB  - PURPOSE: Elements in the endocytic process that are determinants of the
      activities of antifolates delivered by folate-receptor alpha (FRalpha) were
      explored. METHODS: Antifolate growth inhibition was assessed with a 1- or 5-day
      exposure in reduced folate carrier-null HeLa cell lines that express a high level
      of FRalpha in the presence or absence of the proton-coupled folate transporter
      (PCFT). pH-dependent rates of dissociation from FRalpha were also determined.
      RESULTS: With a 1-day drug exposure which is relevant to the pulse clinical
      administration of these drugs, FRalpha expression enhanced raltitrexed activity
      and modestly enhanced ZD9331 activity, but did not significantly augment the
      activity of pemetrexed or lomotrexol. With a 5-day drug exposure, FRalpha
      mediated growth inhibition was increased for raltitrexed and ZD9331 and emerged
      for lomotrexol. While the FRalpha-augmented activity of lomotrexol and
      raltitrexed did not require PCFT, augmentation of ZD9331 activity required the co
      expression of PCFT with both 1- and 5-day exposures. In contrast, there was no
      augmentation of pemetrexed activity by FRalpha under any condition. The
      activities of these agents correlated with their rate of dissociation from the
      receptor at acidic pH: raltitrexed > ZD9331 > lomotrexol > pemetrexed consistent
      with insufficient pemetrexed release from FRalpha for export from the endosomes.
      CONCLUSIONS: FRalpha is unlikely to contribute to the pharmacological activity of
      antifolates, such as pemetrexed, that bind tightly to, and dissociate slowly
      from, the receptor particularly when the exposure time is brief. While PCFT was
      required for FRalpha-mediated ZD9931 activity, the activities of the other
      antifolates was independent of PCFT.

PMID- 25847482
TI  - Association between electrocardiographic findings, right heart strain, and short
      term adverse clinical events in patients with acute pulmonary embolism.
AB  - BACKGROUND: Electrocardiographic (ECG) changes may be seen with pulmonary emboli
      (PE). Whether ECG is associated with short-term adverse clinical events after PE
      is less well established. HYPOTHESIS: ECG findings are associated with short-term
      clinical deterioration after PE. METHODS: Consecutive adult PE patients were
      enrolled in an academic emergency department from 2008 to 2011. The primary
      outcome was right heart strain (RHS) on echocardiogram or CT pulmonary
      angiography, or TnT >=0.1 ng/mL. We derived an ECG (TwiST) score that is
      associated with RHS and short-term adverse clinical events. RESULTS: We enrolled
      298 patients with PE. On multivariate analysis, T-wave inversion in leads V(1)
      through V(3) (OR: 4.7, 95% confidence interval [CI]: 1.7-13.2), S wave in lead I
      (OR: 2.0, 95% CI: 1.1-3.5), and tachycardia (OR: 2.5, 95% CI: 1.3-4.8) were
      associated with RHS. A TwiST score <=2 (n = 210, 72%) was 84% (95% CI: 77%-90%)
      sensitive for the absence of RHS, whereas a TwiST score >=5 (n = 47, 16%) was 93%
      (95% CI: 88%-97%) specific for the presence of RHS. CONCLUSIONS: A simple ECG
      (TwiST) score can identify patients likely or not likely to have RHS with >80%
      specificity and sensitivity and may assist in identifying patients with acute PE
      at risk for adverse clinical events before pursuing other advanced imaging tests.

PMID- 25847481
TI  - Clinical and molecular delineation of Tetrasomy 9p syndrome: report of 12 new
      cases and literature review.
AB  - Tetrasomy 9p is a generic term describing the presence of a supernumerary
      chromosome incorporating two copies of the 9p arm. Two varieties exist:
      isodicentric chromosome 9p (i(9p)), where the two 9p arms are linked by a single
      centromeric region, and pseudodicentric 9p (idic(9p)), where one active and one
      inactive centromere are linked together by a proximal segment of 9q that may
      incorporate euchromatic material. In living patients, i(9p) and idic(9p) are
      usually present in a mosaic state. Fifty-four cases, including fetuses, have been
      reported, of which only two have been molecularly characterized using array-CGH.
      Tetrasomy 9p leads to a variable phenotype ranging from multiple congenital
      anomalies with severe intellectual disability and growth delay to subnormal
      cognitive and physical developments. Hypertelorism, abnormal ears,
      microretrognathia and bulbous nose are the most common dysmorphic traits.
      Microcephaly, growth retardation, joint dislocation, scoliosis, cardiac and renal
      anomalies were reported in several cases. Those physical anomalies are often, but
      not universally, accompanied by intellectual disability. The most recurrent
      breakpoints, defined by conventional cytogenetics, are 9p10, 9q12 and 9q13. We
      report on 12 new patients with tetrasomy 9p (3 i(9p), 8 idic(9p) and one
      structurally uncharacterized), including the first case of parental germline
      mosaicism. All rearrangements have been characterized by DNA microarray. Based on
      our results and a review of the literature, we further delineate the prenatal and
      postnatal clinical spectrum of this imbalance. Our results show poor genotype
      phenotype correlations and underline the need of precise molecular
      characterization of the supernumerary marker.

PMID- 25847483
TI  - F4+ enterotoxigenic Escherichia coli (ETEC) adhesion mediated by the major
      fimbrial subunit FaeG.
AB  - The FaeG subunit is the major constituent of F4(+) fimbriae, associated with
      glycoprotein and/or glycolipid receptor recognition and majorly contributes to
      the pathogen attachment to the host cells. To investigate the key factor involved
      in the fimbrial binding of F4(+) Escherichia coli, both the recombinant E. coli
      SE5000 strains carrying the fae operon gene clusters that express the different
      types of fimbriae in vitro, named as rF4ab, rF4ac, and rF4ad, respectively,
      corresponding to the fimbrial types F4ab, F4ac, and F4ad, and the three isogenic
      in-frame faeG gene deletion mutants were constructed. The adhesion assays and
      adhesion inhibition assays showed that DeltafaeG mutants had a significant
      reduction in the binding to porcine brush border as well as the intestinal
      epithelial cell lines, while the complemented strain DeltafaeG/pfaeG restored the
      adhesion function. The recombinant bacterial strains rF4ab, rF4ac, and rF4ad have
      the same binding property as wild-type F4(+) E. coli strains do and improvement
      in terms of binding to porcine brush border and the intestinal epithelial cells,
      and the adherence was blocked by the monoclonal antibody anti-F4 fimbriae. These
      data demonstrate that the fimbrial binding of F4(+) E. coli is directly mediated
      by the major FaeG subunit. 

PMID- 25847485
TI  - High sulfur content polymer nanoparticles obtained from interfacial
      polymerization of sodium polysulfide and 1,2,3-trichloropropane in water.
AB  - Sulfur-rich materials have recently attracted keen interest for their potentials
      in optical, electrochemical, and pesticidal applications as well as their utility
      in dynamic covalent bond chemistry. Many sulfur-rich polymers, however, are
      insoluble and processing methods are therefore very limited. The synthesis and
      characterization of water-dispersible polymer nanoparticles (NPs) with the sulfur
      content exceeding 75% by weight, obtained from the interfacial polymerization
      between 1,2,3-trichloropropane and sodium polysulfide in water is reported here.
      The interfacial polymerization yields well-defined sulfur-rich NPs in the
      presence of surfactants, which are capable of serving a dual role as a phase
      transfer catalyst on top of emulsifiers. Such dual role allows for the control of
      the product NP size by varying its concentration. The surfactants can be easily
      removed by centrifugation and redispersion in water is also reported here. The
      resulting sulfur-rich NPs are characterized through elemental analysis, dynamic
      light scattering, zeta-potential measurements, and scanning electron microscopy.

PMID- 25847484
TI  - The impact of neighborhood social and built environment factors across the cancer
      continuum: Current research, methodological considerations, and future
      directions.
AB  - Neighborhood social and built environments have been recognized as important
      contexts in which health is shaped. The authors reviewed the extent to which
      these neighborhood factors have been addressed in population-level cancer
      research by scanning the literature for research focused on specific social
      and/or built environment characteristics and their association with outcomes
      across the cancer continuum, including incidence, diagnosis, treatment,
      survivorship, and survival. The commonalities and differences in methodologies
      across studies, the current challenges in research methodology, and future
      directions in this research also were addressed. The assessment of social and
      built environment factors in relation to cancer is a relatively new field, with
      82% of the 34 reviewed articles published since 2010. Across the wide range of
      social and built environment exposures and cancer outcomes considered by the
      studies, numerous associations were reported. However, the directions and
      magnitudes of associations varied, in large part because of the variation in
      cancer sites and outcomes studied, but also likely because of differences in
      study populations, geographic regions, and, importantly, choice of neighborhood
      measures and geographic scales. The authors recommend that future studies
      consider the life-course implications of cancer incidence and survival, integrate
      secondary and self-report data, consider work neighborhood environments, and
      further develop analytical and statistical approaches appropriate to the
      geospatial and multilevel nature of the data. Incorporating social and built
      environment factors into research on cancer etiology and outcomes can provide
      insights into disease processes, identify vulnerable populations, and generate
      results with translational impact of relevance for interventionists and policy
      makers.

PMID- 25847486
TI  - Macroeconomics of Natural Disasters: Strengths and Weaknesses of Meta-Analysis
      Versus Review of Literature.
AB  - We use the case of the macroeconomic impact of natural disasters to analyze
      strengths and weaknesses of meta-analysis in an emerging research field.
      Macroeconomists have published on this issue since 2002 (we identified 60 studies
      to date). The results of the studies are contradictory and therefore the need to
      synthesize the available research is evident. Meta-analysis is a useful method in
      this field. An important aim of our article is to show how one can use the
      identified methodological characteristics to better understand the robustness and
      importance of new findings. To provide a comparative perspective, we contrast our
      meta-analysis and its findings with the major influential research synthesis in
      the field: the IPCC's 2012 special report Managing the Risks of Extreme Events
      and Disasters to Advance Climate Change Adaptation. We show that the IPCC could
      have been more confident about the negative economic impact of disasters and more
      transparent on inclusion and qualification of studies, if it had been
      complemented by a meta-analysis. Our meta-analysis shows that, controlling for
      modeling strategies and data set, the impact of disasters is significantly
      negative. The evidence is strongest for direct costs studies where we see no
      difference between our larger sample and the studies included in the IPCC report.
      Direct cost studies and indirect cost studies differ significantly, both in terms
      of the confidence that can be attached to a negative impact of natural disasters
      and in terms of the sources of heterogeneity of the findings reported in the
      primary studies. 

PMID- 25847487
TI  - Strontium-impregnated bioabsorbable composite for osteoporotic fracture fixation.
AB  - Osteoporosis impairs the bone-healing process as well as bone fracture fixation.
      The intervention of osteoporosis is considered to be one part of bone fracture
      treatment. Thus, orthopedic fixators impregnated with antiosteoporosis regimens
      will improve fracture fixation in osteoporotic bone. In this study, the strontium
      (Sr) and calcium phosphate ceramic (CPC) were mixed first and then mixed with
      poly(epsilon-caprolactone) (PCL) to fabricate a bioactive and bioabsorbable bone
      fixators. The prepared Sr-CPC/PCL screws were implanted into the distal femur of
      ovariectomized rabbits. The results showed that Sr-CPC/PCL composite had the
      appropriate mechanical properties, good biocompatibility, and radio-opacity. The
      Sr addition created a porous structure and accelerated the degradation of bone
      screws, but the degradation products did not acidify the surrounding environment.
      For osteoporotic animals, favorable osteointegration around the Sr-CPC/PCL screws
      was found, and the total porosity of trabecular bone was decreased under the
      inspections of micro-computerized tomography. Compared with PCL or CPC/PCL screw,
      animals which received Sr-CPC/PCL were found to have better results in terms of
      trabecular number, thickness, and separation. This study reveals that the Sr
      impregnated bone fixator improves osseointegration in osteoporotic animals. Sr
      CPC/PCL composite is a good candidate material for osteofixation in osteoporotic
      patients.

PMID- 25847488
TI  - Maternal vitamin D levels are inversely related to allergic sensitization and
      atopic diseases in early childhood.
AB  - BACKGROUND: There are few studies addressing the impact of maternal vitamin D
      status on the vitamin D levels in offspring, their sensitization to common
      allergens and atopic disease development. METHODS: Children aged 0 through 4 yr
      from a birth cohort in the Prediction of Allergies in Taiwanese Children (PATCH)
      study were enrolled. Time series of serum 25-hydroxyvitamin D (25(OH)D) levels
      were measured in maternal blood before delivery, cord blood, and at age 1.5, 3,
      and 4 using an electrochemiluminescence-based assay. Specific IgE antibodies
      against food and inhalant allergens were measured at 6 months, and 1, 1.5, 2, 3,
      and 4 yr of age. RESULTS: A total of 164 mother-child pairs from a birth cohort
      were recruited in this study. The mean levels of maternal 25(OH)D were 23.2 +/-
      7.7 ng/ml with a high (up to 80%) prevalence of insufficient vitamin D status (<
      30 ng/ml). A significant correlation was seen between maternal and cord blood
      25(OH)D levels (p < 0.001), and a persistent lower 25(OH)D level was found in
      children born to mothers with deficient 25(OH)D levels. Deficient maternal
      25(OH)D levels (<20 ng/ml) appeared to be associated with a higher prevalence of
      allergen sensitization before age 2. Higher maternal 25(OH)D levels were
      significantly associated with lower risk of eczema (OR 0.12; 95% CI 0.02-0.63; p
      = 0.012) and asthma (OR 0.22; 95% CI 0.06-0.92; p = 0.038) at age 4. CONCLUSIONS:
      Low maternal 25(OH)D levels appear not only to be associated with an increase in
      the prevalence of allergic sensitization but also the risk of eczema and asthma
      in early childhood.

PMID- 25847490
TI  - Characterization and evolutionary analysis of tributyltin-binding protein and
      pufferfish saxitoxin and tetrodotoxin-binding protein genes in toxic and nontoxic
      pufferfishes.
AB  - Understanding the evolutionary mechanisms of toxin accumulation in pufferfishes
      has been long-standing problem in toxicology and evolutionary biology. Pufferfish
      saxitoxin and tetrodotoxin-binding protein (PSTBP) is involved in the transport
      and accumulation of tetrodotoxin and is one of the most intriguing proteins
      related to the toxicity of pufferfishes. PSTBPs are fusion proteins consisting of
      two tandem repeated tributyltin-binding protein type 2 (TBT-bp2) domains. In this
      study, we examined the evolutionary dynamics of TBT-bp2 and PSTBP genes to
      understand the evolution of toxin accumulation in pufferfishes. Database searches
      and/or PCR-based cDNA cloning in nine pufferfish species (6 toxic and 3 nontoxic)
      revealed that all species possessed one or more TBT-bp2 genes, but PSTBP genes
      were found only in 5 toxic species belonging to genus Takifugu. These toxic
      Takifugu species possessed two or three copies of PSTBP genes. Phylogenetic
      analysis of TBT-bp2 and PSTBP genes suggested that PSTBPs evolved in the common
      ancestor of Takifugu species by repeated duplications and fusions of TBT-bp2
      genes. In addition, a detailed comparison of Takifugu TBT-bp2 and PSTBP gene
      sequences detected a signature of positive selection under the pressure of gene
      conversion. The complicated evolutionary dynamics of TBT-bp2 and PSTBP genes may
      reflect the diversity of toxicity in pufferfishes.

PMID- 25847489
TI  - Sann-Joong-Kuey-Jian-Tang induces autophagy in HepG2 cells via regulation of the
      phosphoinositide-3 kinase/Akt/mammalian target of rapamycin and p38 mitogen
      activated protein kinase pathways.
AB  - Sann-Joong-Kuey-Jian-Tang (SJKJT), a traditional Chinese medicine, was previously
      reported to induce autophagy and inhibit the proliferation of the human HepG2
      hepatocellular carcinoma cell line via an extrinsic pathway. In the present
      study, the effects of SJKJT-induced autophagy and the cytotoxic mechanisms
      mediating these effects were investigated in HepG2 cells. The cytotoxicity of
      SJKJT in the HepG2 cells was evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide assay. The results demonstrated that the half-maximal
      inhibitory concentration of SJKJT was 2.91 mg/ml at 24 h, 1.64 mg/ml at 48 h and
      1.26 mg/ml at 72 h. The results of confocal fluorescence microscopy indicated
      that SJKJT resulted in the accumulation of green fluorescent protein-LC3 and
      vacuolation of the cytoplasm. Flow cytometric analysis revealed the accumulation
      of acidic vesicular organelles. Furthermore, western blot analysis, used to
      determine the expression levels of autophagy-associated proteins, demonstrated
      that the HepG2 cells treated with SJKJT exhibited LC3B-I/LC3B-II conversion,
      increased expression levels of Beclin, Atg-3 and Atg-5 and reduced expression
      levels of p62 and decreased signaling of the phosphoinositide-3
      kinase/Akt/mammalian target of rapamycin and the p38 mitogen-activated protein
      kinase pathways. Taken together, these findings may assist in the development of
      novel chemotherapeutic agents for the treatment of malignant types of liver
      cancer.

PMID- 25847491
TI  - Ground to conduct: mechanochemical synthesis of a metal-organic framework with
      high proton conductivity.
AB  - We report a high proton-conducting material prepared for the first time by
      economical and environmentally-friendly mechanochemistry. Structural elucidation
      of the material from powder X-ray diffraction data reveals the details of the
      solid-state reaction. The reaction represents a new synthetic strategy towards
      materials related to fuel cell technology. 

PMID- 25847496
TI  - Editorial comment: Peyronie's disease and autoimmunity-a real-life clinical study
      and comprehensive review.

PMID- 25847497
TI  - A decade of research using the CASP scale: key findings and future directions.
AB  - Since the publication of A Measure of Quality of Life in Early Old Age: The
      Theory, Development and Properties of a Needs Satisfaction Model (CASP-19) just
      over 10 years ago, the scale has gone on to be used in a wide variety of studies
      in over 20 countries across the world and the original paper has become the most
      highly cited paper for Aging and Mental Health. Therefore it was felt that it was
      a good time to look back and reflect on the developments in the use of the scale
      as well as to look forward to what new research is being done and could be done
      with the measure. To this end we are extremely grateful for the editors for
      allowing us to bring together a collection of papers that represent cutting edge
      research using the CASP scale. These papers cover a wide variety of issues, from
      working conditions to religiosity, from a range of countries, covering Western
      and Eastern Europe as well as Africa. Each makes an important individual
      contribution to our understanding of the factors that influence quality of life
      in later life as well as pointing to the limitations of the measure and future
      work that can be done in this area. 

PMID- 25847499
TI  - Functional role of water in membranes updated: A tribute to Trauble.
AB  - The classical view of a cell membrane is as a hydrophobic slab in which only
      nonpolar solutes can dissolve and permeate. However, water-soluble non
      electrolytes such as glycerol, erythritol, urea and others can permeate lipid
      membranes in the liquid crystalline state. Moreover, recently polar amino acid's
      penetration has been explained by means of molecular dynamics in which appearance
      of water pockets is postulated. According to Trauble (1971), water diffuses
      across the lipid membranes by occupying holes formed in the lipid matrix due to
      fluctuations of the acyl chain trans-gauche isomers. These holes, named "kinks"
      have the molecular dimension of CH2 vacancies. The condensation of kinks may form
      aqueous spaces into which molecular species of the size of low molecular weight
      can dissolve. This molecular view can explain permeability properties considering
      that water may be distributed along the hydrocarbon chains in the lipid matrix.
      The purpose of this review is to consolidate the mechanism anticipated by Trauble
      by discussing recent data in literature that directly correlates the molecular
      state of methylene groups of the lipids with the state of water in each of them.
      In addition, the structural properties of water near the lipid residues can be
      related with the water activity triggering kink formation by changes in the head
      group conformation that induces the propagation along the acyl chains and hence
      to the diffusion of water. 

PMID- 25847500
TI  - The effectiveness of lung cancer MDT and the role of respiratory physicians.
AB  - There is an increasing trend for the use of multi-disciplinary teams (MDT) in the
      management of complex medical conditions. The latter may include various cancers,
      including lung cancer. However, the use of MDT is not restricted to cancer
      management, but may include complex conditions like diabetes and other non
      malignant disorders. There is an increasing trend to use MDT in the investigation
      and management of patients with suspected or proven lung cancer. This review
      examines the evidence that supports the efficacy, or otherwise, of lung cancer
      management in a MDT as opposed to individual care, who should be a member of a
      lung cancer MDT, and the specific role of the respiratory physician in a lung
      cancer MDT. Although it may seem to make common sense to manage lung cancer in a
      MDT setting, there is actually little in the way of high quality data to support
      this concept. The logistic and ethical difficulties in researching this issue are
      highlighted in this review. 

PMID- 25847501
TI  - Current and future status of the use of transgenes for pest management.

PMID- 25847498
TI  - Functional mechanisms of neurotransmitter transporters regulated by lipid-protein
      interactions of their terminal loops.
AB  - The physiological functions of neurotransmitter:sodium symporters (NSS) in
      reuptake of neurotransmitters from the synapse into the presynaptic nerve have
      been shown to be complemented by their involvement, together with non-plasma
      membrane neurotransmitter transporters, in the reverse transport of substrate
      (efflux) in response to psychostimulants. Recent experimental evidence implicates
      highly anionic phosphatidylinositol 4,5-biphosphate (PIP(2)) lipids in such
      functions of the serotonin (SERT) and dopamine (DAT) transporters. Thus, for both
      SERT and DAT, neurotransmitter efflux has been shown to be strongly regulated by
      the presence of PIP(2) lipids in the plasma membrane, and the electrostatic
      interaction of the N-terminal region of DAT with the negatively charged PIP(2)
      lipids. We examine the experimentally established phenotypes in a structural
      context obtained from computational modeling based on recent crystallographic
      data. The results are shown to set the stage for a mechanistic understanding of
      physiological actions of neurotransmitter transporters in the NSS family of
      membrane proteins. This article is part of a Special Issue entitled: Lipid
      protein interactions.

PMID- 25847502
TI  - Analysis of phenazepam and 3-hydroxyphenazepam in post-mortem fluids and tissues.
AB  - Phenazepam is a benzodiazepine that is predominantly used clinically in the
      former Soviet states but is being abused throughout the wider world. This study
      reports the tissue distribution and concentration of both phenazepam and 3
      hydroxyphenazepam in 29 cases quantitated by liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) in a variety of post-mortem fluids (subclavian blood,
      femoral blood, cardiac blood, urine, vitreous humour) and tissues (thalamus,
      liver and psoas muscle). In 27 cases, the cause of death was not directly related
      to phenazepam (preserved (fluoride/oxalate) femoral blood phenazepam
      concentrations 0.007 mg/L to 0.360 mg/L (median 0.097 mg/L). In two cases,
      phenazepam was either a contributing factor to, or the certified cause of death
      (preserved (fluoride/oxalate) femoral blood 0.97 mg/L and 1.64 mg/L). The
      analysis of phenazepam and 3-hydroxyphenazepam in this study suggests that they
      are unlikely to be subject to large post-mortem redistribution and that there is
      no direct correlation between tissues/fluid and femoral blood concentrations.
      Preliminary investigations of phenazepam stability comparing femoral blood
      phenazepam concentrations in paired preserved (2.5% fluoride/oxalate) and
      unpreserved blood show that unpreserved samples show on average a 14% lower
      concentration of phenazepam and we recommend that phenazepam quantitation is
      carried out using preserved samples wherever possible.

PMID- 25847503
TI  - Autologous platelet-rich gel for treatment of diabetic chronic refractory
      cutaneous ulcers: A prospective, randomized clinical trial.
AB  - The purpose of the study is to examine the safety and effectiveness of topical
      autologous platelet-rich gel (APG) application on facilitating the healing of
      diabetic chronic refractory cutaneous ulcers. The study was designed as a
      prospective, randomized controlled trial between January 1, 2007 and December 31,
      2011. Eligible inpatients at the Diabetic Foot Care Center of West China
      Hospital, Sichuan University (China) were randomly prescribed with a 12-week
      standard treatment of ulcers (the control group) or standard treatment plus
      topical application APG (the APG group). The wound healing grades (primary
      endpoint), time to complete healing, and healing velocity within 12 weeks were
      monitored as short-term effectiveness measurements, while side effects were
      documented safety endpoints. The rates of survival and recurrence within the
      follow up were recorded as long-term effectiveness endpoints. Analysis on total
      diabetic ulcers (DUs) (n = 117) and subgroup analysis on diabetic foot ulcers
      (DFUs) (n = 103) were both conducted. Standard treatment plus APG treatment was
      statistically more effective than standard treatment (p < 0.05 in both total DUs
      and subgroup of DFUs). The subjects defined as healing grade 1 were 50/59 (84.8%)
      in total DUs and 41/48 (85.4%) in DFUs in the APG group compared with 40/58
      (69.0%) and 37/55 (67.3%) in the control group from intent to treat population.
      The Kaplan-Meier time-to-healing were significantly different between the two
      groups (p < 0.05 in both total DUs and subgroup of DFUs). No side effects were
      identified after topical APG application. The long-term survival and recurrence
      rates were comparative between groups (p > 0.05). This study shows that topical
      APG application plus standard treatment is safe and quite effective on diabetic
      chronic refractory cutaneous ulcers, compared with standard treatment.

PMID- 25847504
TI  - The effects of alpha-lipoic acid on breast of female albino rats exposed to
      malathion: Histopathological and immunohistochemical study.
AB  - BACKGROUND: The wide use of the organophosphate insecticide malathion is
      accompanied by the risk of human exposure and may be involved in the etiology of
      breast cancers, especially in developing countries. Alpha (alpha)-lipoic acid, a
      natural molecule, present in our diet has antioxidant and protective effects in
      cases such as aging, diabetes mellitus, and vascular and neurodegenerative
      diseases all in which free radicals are involved. However, there is only scarce
      data regarding the efficacy and biological activity of alpha-lipoic acid on
      malathion-induced breast histopathological changes. AIMS: To investigate whether
      malathion can induce mammary histopathological changes, to immunohistochemically
      analyze the modulations in proliferation-apoptosis balance associated with these
      changes, to assess the associated metabolic parameters, antioxidant stress and
      hormonal profile changes and to elucidate the possible protective effect of alpha
      lipoic acid on malathion induced alterations in rats. MATERIALS AND METHODS:
      Forty Wistar female rats weighing 150-170g were divided into four groups. Group
      1: control group were injected intraperitoneally (ip) with saline solution.
      Group2: animals were injected (ip) with malathion twice a day for five days.
      Group 3: animals were orally given alpha-lipoic acid, after three hours of
      treatment with malathion at the same dose given to group 2. Group 4: animals were
      treated with alpha-lipoic acid at the same dose given to group 3. Rats were
      sacrificed on the 90th day, and breast tissues were analyzed for
      histopathological and immunohistochemical alterations. Blood samples were
      collected for biochemical tests. RESULTS: alpha-Lipoic acid exhibited a striking
      reduction of malathion-induced mammary tumor incidence, and reversed intra-tumor
      histopathological alterations. Alpha lipoic acid suppressed proliferating cell
      nuclear antigen (PCNA) and p53 expression, induced apoptosis, upregulated
      proapoptotic protein Bax. CONCLUSIONS: Our results provide the experimental
      evidence that alpha-lipoic acid exerts chemopreventive effect in the breast
      hyperplastic and malignant changes by suppressing abnormal cell proliferation and
      inducing apoptosis with an oncostatic effects during an early-stage breast
      cancer.

PMID- 25847505
TI  - Respiratory syncytial virus infection of airway cells: Role of microRNAs.
AB  - MicroRNAs (miRNAs) are small single-stranded RNA molecules involved in the
      regulation of gene expression at the post-transcriptional level. In the airways,
      miRNAs are implicated in the modulation of antiviral defense, through modulation
      of both innate and adaptive immune response in inflammatory and immune effector
      cells but also in parenchymal cells. The first target of respiratory viruses are
      airway epithelial cells. Following infection, an altered expression of distinct
      miRNAs occurs in airway cells aimed at inhibiting viral replication and
      preserving the airway epithelial barrier, while at the same time viruses induce
      or repress the expression of other miRNAs that favor viral replication.
      Understanding the changes in miRNA expression profile, identification of miRNAs
      target genes and their contribution to the pathogenesis of the disease may help
      the intricate mechanisms of virus-host interaction. Further understanding of
      these molecular mechanisms could lead to development of new antiviral treatments
      in common, high impact, respiratory disorders for which specific treatments are
      not available. Respiratory syncytial virus (RSV) airway infection is a common
      example of virus modifying miRNAs expression to favor immune evasion, and
      constitutes the salient feature of this review.

PMID- 25847506
TI  - Hyperoxia-induced preconditioning against renal ischemic injury is mediated by
      reactive oxygen species but not related to heat shock proteins 70 and 32.
AB  - OBJECTIVE: Pre-exposure of rats to normobaric hyperoxia (O2 >= 95%) may induce
      late preconditioning against renal ischemia-reperfusion (IR) injury. In this
      study we investigated probable mechanisms of IR injury such as the role of
      reactive oxygen species (ROS), renal antioxidant agents, and heat shock proteins
      (HSP) 32 and 70 during delayed hyperoxia-preconditioning (HO). METHODS: Fifty-two
      rats were divided into 7 groups: (A) IR, (B) HO + IR, (C) mercaptopropionyl
      glycine (MPG) + HO + IR, (D) MPG + IR, (E) HO + sham, (F) MPG + sham, and (G)
      sham. Rats in the following study groups (group B, C and E) were kept in a
      normobaric hyperoxic environment for 4 h/day for 6 consecutive days, after which
      they were subjected to 40 minutes of ischemia; animals in the control group
      (group A, D, F, and G) were kept in a normoxic cage. At the end of the
      preconditioning period, 24 hours of reperfusion was performed. Renal function was
      assessed by measuring serum creatinine (Cr), blood urea nitrogen (BUN), and
      creatinine clearance (CLCr). Induction of the antioxidant system was evaluated by
      measuring renal catalase (CAT) and superoxide dismutase (SOD) activities and
      glutathione (GSH) and malondialdehyde (MDA) content. The role of ROS was
      investigated by use of MPG (a ROS scavenger). HSP32 & 70 mRNA and protein also
      were determined. RESULTS: The hyperoxia-preconditioned IR group (B) had a lower
      plasma Cr and BUN and greater CLCr compared with the IR group (A) (P <= .016).
      Administration of MPG led to an increase in plasma Cr and BUN and a decrease in
      CLCr in group C compared with the hyperoxia-preconditioned group B (P <= .004).
      The hyperoxia-preconditioned IR group had a greater CAT activity and GSH level
      compared with the IR group A (P <= .007), whereas the administration of MPG did
      not change the GSH level but led to a decrease in CAT activity in group D
      compared with group B (P < .001). SOD activity did not change in hyperoxia
      preconditioned ischemic rats compared with ischemic rats. Hyperoxia
      preconditioning and MPG administration in ischemic animals did not result in any
      considerable change in MDA level compared with the IR group A. Also, there were
      no clinically relevant differences in HSP32 & 70 mRNA and protein between all
      groups. CONCLUSION: The present study demonstrates that repeated pre-exposure to
      hyperoxia can decrease subsequent renal IR damage in this rat model of renal
      ischemia. Free radical production after hyperoxia appears to play a pivotal role
      in the hyperoxia-induced renal protection independent of HSP level. Antioxidant
      enzyme activities and especially catalase seem to be implicated in this renal
      protective mechanism.

PMID- 25847508
TI  - Feature Page.

PMID- 25847507
TI  - The association of single nucleotide polymorphisms in the connective tissue
      growth factor gene with pseudoexfoliation syndrome/glaucoma.

PMID- 25847509
TI  - Sofosbuvir plus pegylated interferon and ribavirin in patients with genotype 1
      hepatitis C virus in whom previous therapy with direct-acting antivirals has
      failed.
AB  - Retreatment of patients who have not achieved sustained virological response
      (SVR) after treatment with investigational direct-acting antiviral agents (DAAs)
      has not been extensively studied. We conducted an open-label trial to assess the
      efficacy and safety of sofosbuvir (SOF) plus pegylated interferon (Peg-IFN) and
      ribavirin (RBV) in patients with genotype 1 hepatitis C virus (HCV) who
      participated in previous studies of one or more Gilead investigational DAAs in
      combination with RBV with or without Peg-IFN. We enrolled 80 patients at 40
      sites. All patients received SOF 400 mg once daily plus Peg-IFN-alpha 180
      MUg/week and weight-based ribavirin (1,000 or 1,200 mg/day) for 12 weeks. The
      efficacy endpoint was the proportion of patients with SVR 12 weeks after
      discontinuation of therapy (SVR12). Of the 80 patients enrolled, 36 (45%) had
      received two or more courses of earlier treatment for HCV and 74 (93%) had at
      least one resistance-associated variant (RAV) at baseline. SVR12 was achieved by
      63 of the 80 patients (79%) treated. Rates of SVR12 were similar across patient
      subgroups. Presence of RAVs at baseline did not appear to be associated with
      treatment failure. Seventy-one of eighty patients (89%) experienced at least one
      adverse event (AE), but most events were mild to moderate in severity. The most
      common AEs were fatigue, headache, and nausea. No patients discontinued all
      treatment because of AEs. CONCLUSION: These findings suggest that SOF plus Peg
      IFN and RBV for 12 weeks is effective and safe in patients who have not achieved
      SVR with earlier regimens of one or more DAAs plus Peg-IFN and RBV.

PMID- 25847511
TI  - SOX7 interferes with beta-catenin activity to promote neuronal apoptosis.
AB  - SOX7 mediates various developmental processes. However, its role in neuronal
      apoptosis remains unclear. In the present study, we investigated the expression
      pattern and role of SOX7 in potassium deprivation-induced rat cerebellar granule
      neuron apoptosis. Our results showed that both mRNA and protein levels of SOX7
      were upregulated when potassium was deprived. SOX7 overexpression promoted
      neuronal apoptosis, whereas knockdown of SOX7 protected neurons against
      apoptosis. Moreover, we found that beta-catenin activity was suppressed during
      apoptosis and that beta-catenin inhibition was crucial for potassium deprivation
      induced neuronal apoptosis. This suppression was mediated by an interaction
      between SOX7 and beta-catenin but not by protein degradation. Lastly, we showed
      that beta-catenin inhibition mediated the pro-apoptotic effect of SOX7. Together,
      our findings demonstrated that SOX7 interfered with beta-catenin activity to
      promote neuronal apoptosis, which acted as a novel signaling mechanism in
      neuronal cell death. 

PMID- 25847510
TI  - Respiratory syncytial virus, an ongoing medical dilemma: an expert commentary on
      respiratory syncytial virus prophylactic and therapeutic pharmaceuticals
      currently in clinical trials.
AB  - As the most important viral cause of severe respiratory disease in infants and
      increasing recognition as important in the elderly and immunocompromised,
      respiratory syncytial virus (RSV) is responsible for a massive health burden
      worldwide. Prophylactic antibodies were successfully developed against RSV.
      However, their use is restricted to a small group of infants considered at high
      risk of severe RSV disease. There is still no specific therapeutics or vaccines
      to combat RSV. As such, it remains a major unmet medical need for most
      individuals. The World Health Organisations International Clinical Trials
      Registry Platform (WHO ICTRP) and PubMed were used to identify and review all RSV
      vaccine, prophylactic and therapeutic candidates currently in clinical trials.
      This review presents an expert commentary on all RSV-specific prophylactic and
      therapeutic candidates that have entered clinical trials since 2008. 

PMID- 25847513
TI  - Assessing the drug release from nanoparticles: Overcoming the shortcomings of
      dialysis by using novel optical techniques and a mathematical model.
AB  - The aim of the present investigation was to develop a reliable method which can
      be applied to the measurement of in vitro drug release from nanocarriers. Since
      the limited membrane transport is one major obstacle to the assessment of drug
      release with dialysis techniques, the determination of this parameter was our
      objective. Therefore, a novel drug release automatic monitoring system (DREAMS)
      was designed to conduct continuous measurements during the dialysis process.
      Moreover, a mathematical model was used for evaluation of the experimental data.
      This combination of mathematical and analytical tools enabled the quantification
      of the total amount of free drug in the system. Eudragit((r)) RS 100
      nanoparticles loaded with the model compound 5,10,15,20-tetrakis(m
      hydroxypheny)chlorin (mTHPC) were investigated and the drug release was
      continuously monitored by using a fluorescence spectrometer that is part of the
      setup. Free drug and drug-loaded nanoparticles were tested to discriminate
      between the two formulations. In addition, two types of membranes composed of
      different materials were evaluated and the kinetics of membrane transport was
      determined. The data obtained from the apparatus were further treated by a
      mathematical model, which yielded distinguishable release profiles between
      samples of different compositions. The method offers a promising option for
      release testing of nanoparticles. 

PMID- 25847514
TI  - Military sexual assault, gender, and PTSD treatment outcomes of U.S. Veterans.
AB  - This study examined whether gender and military sexual assault (MSA) were
      associated with psychiatric severity differences at initiation of treatment for
      posttraumatic stress disorder (PTSD) and whether MSA and gender predicted
      psychiatric treatment outcomes. Male (n = 726) and female (n = 111) patients were
      recruited from 7 U.S. Department of Veterans Affairs (VA) PTSD specialty
      intensive treatment programs and completed an intake survey; 69% (n = 574) of the
      participants completed a 4-month postdischarge follow-up survey. Measures
      included current PTSD and depressive symptoms, aggressive/violent behaviors,
      alcohol and drug use severity, and quality of life. Multilevel multivariate
      regression analyses were conducted to examine the main and interaction effects of
      gender and MSA on psychiatric treatment outcomes at 4-month follow-up, including
      demographics, baseline severity, hostile fire, and treatment length of stay.
      Baseline PTSD severity did not differ by gender or MSA status, but women had more
      severe depressive symptoms (d = 0.40) and less aggressive/violent symptoms (d = 
      0.46) than men. Gender, MSA status, and the interaction between gender and MSA
      did not predict treatment outcomes as hypothesized. Male and female veterans with
      and without MSA responded equally well to treatment in VA PTSD intensive
      treatment programs.

PMID- 25847515
TI  - Management of massive bone loss in infected reverse shoulder arthroplasty using
      an articulating hip antibiotic spacer: a case report.

PMID- 25847512
TI  - Accuracy of multiecho magnitude-based MRI (M-MRI) for estimation of hepatic
      proton density fat fraction (PDFF) in children.
AB  - PURPOSE: To assess accuracy of magnitude-based magnetic resonance imaging (M-MRI)
      in children to estimate hepatic proton density fat fraction (PDFF) using two to
      six echoes, with magnetic resonance spectroscopy (MRS) -measured PDFF as a
      reference standard. METHODS: This was an IRB-approved, HIPAA-compliant, single
      center, cross-sectional, retrospective analysis of data collected prospectively
      between 2008 and 2013 in children with known or suspected nonalcoholic fatty
      liver disease (NAFLD). Two hundred eighty-six children (8-20 [mean 14.2 +/- 2.5]
      years; 182 boys) underwent same-day MRS and M-MRI. Unenhanced two-dimensional
      axial spoiled gradient-recalled-echo images at six echo times were obtained at 3T
      after a single low-flip-angle (10 degrees ) excitation with >= 120-ms recovery
      time. Hepatic PDFF was estimated using the first two, three, four, five, and all
      six echoes. For each number of echoes, accuracy of M-MRI to estimate PDFF was
      assessed by linear regression with MRS-PDFF as reference standard. Accuracy
      metrics were regression intercept, slope, average bias, and R(2) . RESULTS: MRS
      PDFF ranged from 0.2-40.4% (mean 13.1 +/- 9.8%). Using three to six echoes,
      regression intercept, slope, and average bias were 0.46-0.96%, 0.99-1.01, and
      0.57-0.89%, respectively. Using two echoes, these values were 2.98%, 0.97, and
      2.72%, respectively. R(2) ranged 0.98-0.99 for all methods. CONCLUSION: Using
      three to six echoes, M-MRI has high accuracy for hepatic PDFF estimation in
      children.

PMID- 25847516
TI  - Biomechanical comparison between the trapezius transfer and latissimus transfer
      for irreparable posterosuperior rotator cuff tears.
AB  - BACKGROUND: The purpose of this study was to characterize the biomechanical
      effects of the lower trapezius transfer and to compare it with the latissimus
      dorsi transfer in a cadaveric model of a massive posterosuperior rotator cuff
      tear. METHODS: Eight cadaveric shoulders were tested at 0 degrees , 30 degrees ,
      and 60 degrees  of shoulder abduction. Range of motion, humeral rotational
      position due to muscle loading, joint reaction forces, and kinematics were
      measured. All specimens were tested in 4 conditions: intact, massive
      posterosuperior cuff tear, lower trapezius transfer, and latissimus dorsi
      transfer. A repeated-measures analysis of variance was used for statistical
      analysis. RESULTS: Internal rotation due to muscle loading increased with massive
      cuff tear compared with the intact condition (P < .05). The latissimus transfer
      corrected this change at 0 degrees  abduction, whereas the trapezius transfer
      corrected this at all abduction angles. The massive cuff tear decreased
      glenohumeral joint compression forces at all abduction angles; these forces were
      restored by the lower trapezius transfer (P < .05). At maximum humeral internal
      rotation and 0 degrees  of abduction, the humeral head apex shifted superiorly
      and laterally with massive cuff tear (P < .05); this shift was more closely
      restored to intact values by the trapezius transfer compared with the latissimus
      transfer (P < .05). CONCLUSION: The lower trapezius transfer is superior to the
      latissimus transfer at restoring native glenohumeral kinematics and joint
      reaction forces in our cadaveric model. It may be a promising treatment option
      for patients with a massive irreparable rotator cuff tear.

PMID- 25847517
TI  - The significance of the clavicle on shoulder girdle function.
AB  - BACKGROUND: Patients with cleidocranial dysplasia (CCD) can have a congenital
      partial or total absence of the clavicle. The aim of this study was to evaluate
      the functional shoulder score in these patients. MATERIAL AND METHODS: Patients
      with CCD who were members of a social media group were invited to take part in an
      Internet-based survey. The questionnaire was composed of 3 general questions, a
      question concerning partial or total absence of the clavicle, and 3 patient-based
      shoulder scores (American Shoulder and Elbow Surgeons score; shortened
      Disabilities of the Arm, Shoulder, and Hand score; and patient-based Constant
      Murley score). RESULTS: Thirty-six patients (27 women, 9 men) with a mean age of
      40 years participated in the survey; 17 patients had a bilateral absence, 16
      patients had a bilateral partial absence, and 3 patients had a total absence on
      one side and a partial absence of the clavicle on the other side. The average
      patient-based Constant-Murley score was 79; shortened Disabilities of the Arm,
      Shoulder, and Hand score, 11; and American Shoulder and Elbow Surgeons score, 93.
      There was no significant difference in the scores between left and right. There
      was no correlation between partial and total absences and the shoulder scores.
      CONCLUSION: Patients with self-reported CCD are subjectively normal to their
      peers when they are evaluated with 3 common shoulder scores. There was no
      correlation between partial and total absences and the shoulder scores.

PMID- 25847518
TI  - Medical procedures and outcomes of Japanese patients with trisomy 18 or trisomy
      13: analysis of a nationwide administrative database of hospitalized patients.
AB  - The choices of aggressive treatment for trisomy 18 (T18) and trisomy 13 (T13)
      remain controversial. Here, we describe the current medical procedures and
      outcomes of patients with T18 and T13 from a nationwide administrative database
      of hospitalized patients in Japan. We used the database to identify eligible
      patients with T18 (n = 438) and T13 (n = 133) who were first admitted to one of
      200 hospitals between July 2010 and March 2013. Patients were divided into
      admission at day <7 (early neonatal) and admission at day >=7 (late neonatal and
      post neonatal) groups, and we described the medical intervention and status at
      discharge for each group. In the day <7 groups, surgical interventions were
      performed for 56 (19.9%) T18 patients and 22 (34.4%) T13 patients, including
      pulmonary artery banding, and procedures for esophageal atresia and omphalocele.
      None received intracardiac surgery. The rate of patients discharged to home was
      higher in the day >=7 groups than the day <7 groups (T18: 72.6 vs. 38.8%; T13:
      73.9 vs. 21.9%, respectively). Our data show that a substantial number of
      patients with trisomy received surgery and were then discharged home, but, of
      these, a considerable number required home medical care. This included home
      oxygen therapy, home mechanical ventilation, and tube feeding. These findings
      will be useful to clinicians or families who care for patients with T18 and T13.

PMID- 25847520
TI  - ISSCR 2013: back to Bean Town.
AB  - The International Society for Stem Cell Research 11(th) Annual Meeting was held
      in Boston in June 2013, bringing together just over 4000 attendees. An emphasis
      on therapeutic applications in many talks reflected the maturation of the stem
      cell field from its origins in basic science to one that is beginning to show
      therapeutic promise.

PMID- 25847521
TI  - Stem cells in translation: impression of the ISSCR Regional Meeting in Florence.
AB  - The International Society for Stem Cell Research hosted an exciting meeting on
      stem cell-based translational medicine in Florence, Italy in September 2013. This
      report gives an overview of recent advances and breakthroughs presented at the
      meeting. 

PMID- 25847522
TI  - Microbial ecology of watery kimchi.
AB  - The biochemistry and microbial ecology of 2 similar types of watery (mul) kimchi,
      containing sliced and unsliced radish and vegetables (nabak and dongchimi,
      respectively), were investigated. Samples from kimchi were fermented at 4, 10,
      and 20  degrees C were analyzed by plating on differential and selective media,
      high-performance liquid chromatography, and high-throughput DNA sequencing of 16S
      rDNA. Nabak kimchi showed similar trends as dongchimi, with increasing lactic and
      acetic acids and decreasing pH for each temperature, but differences in
      microbiota were apparent. Interestingly, bacteria from the Proteobacterium
      phylum, including Enterobacteriaceae, decreased more rapidly during fermentation
      at 4  degrees C in nabak cabbage fermentations compared with dongchimi. Although
      changes for Proteobacterium and Enterobacteriaceae populations were similar
      during fermentation at 10 and 20  degrees C, the homolactic stage of fermentation
      did not develop for the 4 and 10  degrees C samples of both nabak and dongchimi
      during the experiment. These data show the differences in biochemistry and
      microbial ecology that can result from preparation method and fermentation
      conditions of the kimchi, which may impact safety (Enterobacteriaceae populations
      may include pathogenic bacteria) and quality (homolactic fermentation can be
      undesirable, if too much acid is produced) of the product. In addition, the data
      also illustrate the need for improved methods for identifying and differentiating
      closely related lactic acid bacteria species using high-throughput sequencing
      methods. 

PMID- 25847523
TI  - Equivocal ALK fluorescence in-situ hybridization (FISH) cases may benefit from
      ancillary ALK FISH probe testing.
AB  - AIMS: Accurate assessment of anaplastic lymphoma kinase (ALK) gene rearrangement
      in non-small-cell lung cancers (NSCLCs) is critical to identify patients who are
      likely to respond to crizotinib. The aim of this study was to evaluate the
      ALK/EML4 TriCheck FISH probe in a series of NSCLCs enriched for tumours with
      equivocal ALK status. METHODS AND RESULTS: ALK FISH was prospectively performed
      on 45 NSCLCs with the ALK/EML4 TriCheck probe (ZytoVision) and the Vysis ALK
      break-apart probe (Abbott Molecular). ALK immunohistochemistry was performed with
      5A4 and D5F3 antibodies. Fourteen cases had equivocal ALK status, based on
      borderline or focal FISH positivity, an atypical FISH pattern, or discrepancy
      between ALK FISH and immunohistochemistry. Four of the 14 equivocal cases showed
      discordance between the two FISH probes. All other cases were concordant. The
      TriCheck probe showed that, of 31 unequivocal cases, 15 were ALK-rearranged, and
      60% of these had EML4 as the translocation partner. Within the group of 14
      equivocal cases, 12 showed rearrangement with the Tricheck probe; only one of
      these showed EML4 rearrangement. Of the six equivocal cases that received
      crizotinib, four showed clinical benefit. CONCLUSIONS: The ALK/EML4 TriCheck FISH
      probe may be useful for the detection of ALK rearrangements, especially in
      borderline or atypical cases, where an additional unique ALK FISH probe may
      provide further confirmation of rearrangement.

PMID- 25847525
TI  - Hysterectomy with radiotherapy or chemotherapy or both for women with locally
      advanced cervical cancer.
AB  - BACKGROUND: Cervical cancer is the second commonest cancer among women up to 65
      years of age and is the most frequent cause of death from gynaecological cancers
      worldwide. Sources suggest that a very high proportion of new cervical cancer
      cases in developing countries are at an advanced stage (IB2 or more) and more
      than a half of these may be stage III or IV. Cervical cancer staging is based on
      findings from clinical examination (FIGO) staging). Standard care in Europe and
      US for stage IB2 to III is non-surgical treatment (chemoradiation). However in
      developing countries, where there is limited access to radiotherapy, locally
      advanced cervical cancer may be treated with a combination of chemotherapy and
      hysterectomy (surgery to remove the womb and the neck of the womb, with or
      without the surrounding tissues). It is not certain if this improves survival.
      Therefore, it is important to systematically assess the value of hysterectomy in
      addition to radiotherapy or chemotherapy, or both, as an alternative intervention
      in the treatment of locally advanced cervical cancer (stage IB2 to III).
      OBJECTIVES: To determine whether hysterectomy, in addition to standard treatment
      with radiation or chemotherapy, or both, in women with locally advanced cervical
      cancer (stage IB2 to III) is safe and effective compared with standard treatment
      alone. SEARCH METHODS: We searched the Cochrane Gynaecological Cancer Group
      Trials Register, CENTRAL, MEDLINE, EMBASE and LILACS up to February 2014. We also
      searched registers of clinical trials, abstracts of scientific meetings and
      reference lists of included studies. SELECTION CRITERIA: We searched for
      randomised controlled trials (RCTs) that compared treatment protocols involving
      hysterectomy versus radiotherapy or chemotherapy, or both, in women with advanced
      stage (IB2 to III) cervical cancer presenting for the first time. DATA COLLECTION
      AND ANALYSIS: We assessed study eligibility independently, extracted data and
      assessed risk of bias. Where possible, overall and progression or disease-free
      survival outcomes were synthesised in a meta-analysis using the random-effects
      model. Adverse events were incompletely reported so results of single trials were
      described in narrative form. MAIN RESULTS: We included seven RCTs (1217 women) of
      varying methodological quality in the review; most trials were at moderate or
      high risk of bias.Three were multi-centre trials, two were single-centre trials,
      and in two trials it was unclear if they were single or multi-centre. These
      trials compared the following interventions for women with locally advanced
      cervical cancer (stages IB2 to III):hysterectomy (simple or radical) with
      radiotherapy (N = 194) versus radiotherapy alone (N = 180); hysterectomy (simple
      or radical) with chemoradiotherapy (N = 31) versus chemoradiotherapy alone (N =
      30); hysterectomy (radical) with chemoradiotherapy (N = 111) versus internal
      radiotherapy with chemoradiotherapy (N = 100); hysterectomy (simple or radical)
      with upfront (neoadjuvant) chemotherapy (N = 298) versus radiotherapy alone (N =
      273).One trial (N = 256) found no difference in the risk of death or disease
      progression between women who received attenuated radiotherapy followed by
      hysterectomy and those who received radiotherapy (external and internal) alone
      (hazard ratio (HR) 0.89, 95% confidence interval (CI) 0.61 to 1.29). This trial
      also reported no difference between the two groups in terms of adverse effects
      (18/129 grade 3 or 4 adverse effects in the hysterectomy and radiation group and
      19 cases in 18/121 women in the radiotherapy alone group). There was no
      difference in 5-year tumour-free actuarial survival (representation of the
      probable years of survivorship of a defined population of participants) or severe
      complications (grade 3) in another trial (N = 118) which reported the same
      comparison (6/62 versus 6/56 in the radiation with surgery group versus the
      radiotherapy alone group, respectively). The quality of the evidence was low for
      all these outcomes.One trial (N = 61) reported no difference (P value > 0.10) in
      overall and recurrence-free survival at 3 years between chemoradiotherapy and
      hysterectomy versus chemoradiotherapy alone (low quality evidence). Adverse
      events and morbidity data were not reported.Similarly, another trial (N = 211)
      found no difference in the risk of death (HR 0.65, 95% CI 0.35 to 1.21, P value =
      0.19, low quality evidence), disease progression (HR 0.70, 95% CI 0.31 to 1.34, P
      value = 0.24, low quality evidence) or severe late complications (P value = 0.53,
      low quality evidence) between women who received internal radiotherapy versus
      hysterectomy after both groups had received external-beam chemoradiotherapy.Meta
      analysis of three trials of neoadjuvant chemotherapy and hysterectomy versus
      radiotherapy alone, assessing 571 participants, found that women who received
      neoadjuvant chemotherapy plus hysterectomy had less risk of death than those who
      received radiotherapy alone (HR 0.71, 95% CI 0.55 to 0.93, I(2) = 0%, moderate
      quality evidence). However, a significant number of the participants that
      received neoadjuvant chemotherapy plus hysterectomy had radiotherapy as well.
      There was no difference in the proportion of women with disease progression or
      recurrence between the two groups (RR 0.75, 95% CI 0.53 to 1.05, I(2) = 20%,
      moderate quality evidence).Results of single trials reported no apparent (P value
      > 0.05) difference in long-term severe complications, grade 3 acute toxicity and
      severe late toxicity between the two groups (low quality evidence).Quality of
      life outcomes were not reported in any of the trials. AUTHORS' CONCLUSIONS: From
      the available RCTs, we found insufficient evidence that hysterectomy with
      radiotherapy, with or without chemotherapy, improves the survival of women with
      locally advanced cervical cancer who are treated with radiotherapy or
      chemoradiotherapy alone. The overall quality of the evidence was variable across
      the different outcomes and was universally downgraded due to concerns about risk
      of bias. The quality of the evidence for neoadjuvant chemotherapy and radical
      hysterectomy versus radiotherapy alone for survival outcomes was moderate, with
      evidence from other comparisons of low quality. This was mainly based on poor
      reporting and sparseness of data where results were based on single trials. More
      trials that assess medical management with and without hysterectomy may test the
      robustness of the findings of this review as further research is likely to have
      an important impact on our confidence in the estimate of effect.

PMID- 25847524
TI  - Presenting phenotype of paediatric inflammatory bowel disease in Wessex, Southern
      England 2010-2013.
AB  - AIM: There has been at least a twofold increase in the incidence of paediatric
      inflammatory bowel disease (PIBD) over the last 20 years; we report the
      presenting features from 2010 to 2013 and compare with previous data. METHODS:
      All patients diagnosed with PIBD at University Hospitals Southampton from 2010 to
      2013 were identified from an in-house database. Data were obtained from paper and
      electronic notes. Height, weight and BMI SDS are presented as median values (95%
      CI). RESULTS: One hundred and seventy-two patients were included (median age at
      diagnosis 13.5, 115 male); Crohn's disease (CD) - 107, UC - 50, inflammatory
      bowel disease unclassified (IBDU) - 15. The most common presenting features of CD
      were abdominal pain (86%), diarrhoea (78.5%) and weight loss (56.1%); 42.1% of
      patients had all three. In UC blood in stool (92%), diarrhoea (92%) and abdominal
      pain (88%) were the most common; all three in 76% of patients. CD presented with
      ileocolonic disease in 52.5%. UC presented with pancolitis in 64%. There was
      growth delay in CD: height -0.37 (-0.60 to -0.14); weight -1.09 (-1.35 to -0.83).
      Growth was maintained in UC: height 0.53 (0.19 to 0.87); weight 0.14 (-0.20 to
      0.48). CONCLUSION: Paediatric inflammatory bowel disease phenotype remains as
      extensive despite increasing incidence. Although the classical phenotype is
      common, a reasonable proportion present with atypical features, normal growth and
      normal blood markers.

PMID- 25847519
TI  - Epigenetics of the failing heart.
AB  - With the impressive advancement in high-throughput 'omics' technologies over the
      past two decades, epigenetic mechanisms have emerged as the regulatory interface
      between the genome and environmental factors. These mechanisms include DNA
      methylation, histone modifications, ATP-dependent chromatin remodeling and RNA
      based mechanisms. Their highly interdependent and coordinated action modulates
      the chromatin structure controlling access of the transcription machinery and
      thereby regulating expression of target genes. Given the rather limited
      proliferative capability of human cardiomyocytes, epigenetic regulation appears
      to play a particularly important role in the myocardium. The highly dynamic
      nature of the epigenome allows the heart to adapt to environmental challenges and
      to respond quickly and properly to cardiac stress. It is now becoming evident
      that histone-modifying and chromatin-remodeling enzymes as well as numerous non
      coding RNAs play critical roles in cardiac development and function, while their
      dysregulation contributes to the onset and development of pathological cardiac
      remodeling culminating in HF. This review focuses on up-to-date knowledge about
      the epigenetic mechanisms and highlights their emerging role in the healthy and
      failing heart. Uncovering the determinants of epigenetic regulation holds great
      promise to accelerate the development of successful new diagnostic and
      therapeutic strategies in human cardiac disease. 

PMID- 25847526
TI  - Differential expression of ethylene biosynthesis genes in drupelets and
      receptacle of raspberry (Rubus idaeus).
AB  - Red Raspberry (Rubus idaeus) is traditionally classified as non-climacteric, and
      the role of ethylene in fruit ripening is not clear. The available information
      indicates that the receptacle, a modified stem that supports the drupelets, is
      involved in ethylene production of ripe fruits. In this study, we report
      receptacle-related ethylene biosynthesis during the ripening of fruits of cv.
      Heritage. In addition, the expression pattern of ethylene biosynthesis
      transcripts was evaluated during the ripening process. The major transcript
      levels of 1-aminocyclopropane-1-carboxylic acid synthase (RiACS1) and 1
      aminocyclopropane-1-carboxylic acid oxidase (RiACO1) were concomitant with
      ethylene production, increased total soluble solids (TSS) and decreased
      titratable acidity (TA) and fruit firmness. Moreover, ethylene biosynthesis and
      transcript levels of RiACS1 and RiACO1 were higher in the receptacle, sustaining
      the receptacle's role as a source of ethylene in regulating the ripening of
      raspberry. 

PMID- 25847527
TI  - NIR Fluorogenic Dye as a Modular Platform for Prodrug Assembly: Real-Time in vivo
      Monitoring of Drug Release.
AB  - The ability to monitor drug release in vivo provides essential pharmacological
      information. We developed a new modular approach for the preparation of
      theranostic prodrugs with a turn-ON near-infrared (NIR) fluorescence mode of
      action. The prodrugs release their chemotherapeutic cargo and an active cyanine
      fluorophore upon reaction with a specific analyte. The prodrug platform is based
      on the fluorogenic dye QCy7; upon removal of a triggering substrate, the dye
      fluoresces, and the free drug is released. The evaluated camptothecin prodrug was
      activated by endogenous hydrogen peroxide produced in tumor cells in vitro and in
      vivo. Drug release and in vitro cytotoxicity were correlated with the emitted
      fluorescence. The prodrug activation was effectively imaged in real time in mice
      bearing tumors. The modular design of the QCy7 fluorogenic platform should allow
      the preparation of numerous other prodrugs with various triggering substrates and
      chemotherapeutic agents. We anticipate that the development of real-time in vivo
      monitoring tools such as that described herein will pave the way for personalized
      therapy. 

PMID- 25847528
TI  - Palladium-catalyzed enantioselective C-H arylation for the synthesis of P
      stereogenic compounds.
AB  - A palladium-catalyzed enantioselective C-H arylation of N-(o-bromoaryl)
      diarylphosphinic amides is described for the synthesis of phosphorus compounds
      bearing a P-stereogenic center. The method provides good enantioselectivities and
      high yields. The products were readily transformed into P-chiral biphenyl
      monophosphine ligands.

PMID- 25847529
TI  - Suppressive effects of exogenous regucalcin on the proliferation of human
      pancreatic cancer MIA PaCa-2 cells in vitro.
AB  - Regucalcin plays a pivotal role as a suppressor protein in signal transduction in
      various types of cells and tissues. The regucalcin gene is localized on the X
      chromosome. and its expression has been shown to be suppressed in various types
      of tumor tissue in animal and human subjects, suggesting a potential role of
      regucalcin in carcinogenesis. This study was undertaken to determine the effects
      of exogenous regucalcin on the proliferation of cloned human pancreatic cancer
      MIA PaCa-2 cells in vitro. The proliferation of the MIA PaCa-2 cells was
      suppressed following culture with regucalcin (0.01-10 nM). Such an effect was
      also observed in pancreatic cancer Pt45P1 cells, that highly expressed tissue
      factor (high TF), or Pt45P1 cells, that highly expressed alternativly spliced
      variants of tissue factor (asTF). In the MIA PaCa-2 cells, the suppressive
      effects of regucalcin on cell proliferation were not enhanced either in the
      presence of tumor necrosis factor-alpha (TNF-alpha), or in the presence of Bay K
      8644, PD98059, staurosporine, wortmannin or 5,6-dichloro-1-beta-D
      ribofuranosylbenzimidazole (DRB). However, this was not the case for gemcitabine,
      which was shown to suppress cell proliferation. Exogenous regucalcin did not
      cause apoptotic cell death in the MIA PaCa-2 cells in vitro. These findings
      demonstrate that exogenous regucalcin exerts suppressive effects on the
      proliferation of human pancreatic MIA PaCa-2 cells and that these effects are
      mediated through the inhibition of various signaling pathways related to nuclear
      factor-kappaB (NF-kappaB), extracellular signal-regulated kinase (ERK), protein
      kinase C, calcium signaling, phosphatidylinositol 3-kinase (PI3K) or nuclear
      transcription activity in vitro. Our data suggest that exogenous regucalcin
      exerts suppressive effects on the proliferation of human pancreatic cancer cells.

PMID- 25847530
TI  - Comprehensive analysis of fatty alcohol ethoxylates by ultra high pressure
      hydrophilic interaction chromatography coupled with ion mobility spectrometry
      mass spectrometry using a custom-designed sub-2 MUm column.
AB  - Comprehensive analysis of fatty alcohol ethoxylates has been conducted by
      coupling ultra high pressure hydrophilic interaction chromatography and ion
      mobility spectrometry mass spectrometry. A custom-designed sub-2 MUm column was
      used for the chromatographic separation of fatty alcohol ethoxylates by
      hydrophilic interaction chromatography. Ion mobility spectrometry provided a post
      ionization resolution during a very short period of 6.4 ms. Distinguishable
      families of singly, doubly, and triply charged fatty alcohol ethoxylates were
      clearly observed. By virtue of the combination of hydrophilic interaction
      chromatography and ion mobility spectrometry, comprehensive resolution based on
      both hydrophobicity difference and mobility disparity has been achieved for fatty
      alcohol ethoxylates. The orthogonality of the developed separation and analysis
      system was evaluated with the correlation coefficient and peak spreading angle of
      0.0224 and 88.72 degrees , respectively. The actual peak capacity obtained was
      individually 40 and 193 times than those when hydrophilic interaction
      chromatography and ion mobility spectrometry were used alone. The collision cross
      sections of fatty alcohol ethoxylates were calculated by calibrating the
      traveling wave ion mobility device with polyalanine. 

PMID- 25847531
TI  - 'I've used the word cancer but it's actually good news': discursive
      performativity of cancer and the identity of urological cancer services.
AB  - Drawing on the ethnographic study of urological cancer services, this article
      explores how a set of particular discourses embedded in the everyday clinical
      work in a large teaching hospital in the UK helps materialise particular
      configurations of cancer and related professional identities. Emerging on the
      intersection of specific socio-material arrangements (cancer survival rates,
      treatment regimens, cancer staging classifications, metaphors, clinical
      specialities) and operating across a number of differential relations
      (curable/incurable, treatable/untreatable, aggressive/nonaggressive), these
      configurations help constitute the categories of 'good' and 'bad' cancers as
      separate and contrasting entities. These categories help materialise particular
      distributions of power and are thus implicated in the making of specific claims
      about the identity of urological cancer services as unique and privileged.
      Exploring these issues in view of feminist and material-semiotic approaches to
      studying science, technology and medicine, this article seeks to move away from
      the understanding of cancer discourses as primarily linguistic performances,
      proposing to see them instead as arrangements of practices and relations
      simultaneously material and semiotic through which particular categories,
      entities and phenomena acquire their determinate nature. In doing so, it seeks to
      contribute to sociology's broader concern with discursive performativity of
      cancer. 

PMID- 25847532
TI  - Living for the moment: men situating risk-taking after the death of a friend.
AB  - The primary cause of death for men under the age of 30 is unintentional injury
      and, despite health-promotion efforts and programme interventions, male injury
      and death rates have not decreased in recent years. Drawing on 22 interviews from
      a study of men, risk and grief, we describe how a risk-related tragedy shaped the
      participants' understandings of and practices of risk-taking. The findings
      indicate that most participants did not alter their perceptions and engagement in
      risky practices, which reflected their alignment to masculine ideals within
      specific communities of practice where risk-taking was normalised and valorised.
      Continued reliance on risky practices following the death of a friend was
      predominantly expressed as 'living for the moment,' where caution and safety were
      framed as conservative practices that undermined and diluted the robustness
      ideally embodied by this subgroup of young men. Two main themes: living life,
      accepting death and upping the ante illustrate how risk-taking can persist
      following a death. A smaller group of participants articulated a different
      viewpoint; reining in risk practices, to describe their risk management
      approaches after the death of a male friend. This novel study confirms the
      ongoing challenge of reducing men's risk-taking practices, even after the death
      of a friend. 

PMID- 25847533
TI  - Expectations in the field of the internet and health: an analysis of claims about
      social networking sites in clinical literature.
AB  - This article adopts a critical sociological perspective to examine the
      expectations surrounding the uses of social networking sites (SNSs) articulated
      in the domain of clinical literature. This emerging body of articles and
      commentaries responds to the recent significant growth in SNS use, and
      constitutes a venue in which the meanings of SNSs and their relation to health
      are negotiated. Our analysis indicates how clinical writing configures the role
      of SNSs in health care through a range of metaphorical constructions that frame
      SNSs as a tool, a conduit for information and a traversable space. The use of
      such metaphors serves not only to describe the new affordances offered by SNSs
      but also posits distinct lay and professional practices, while reviving a range
      of celebratory claims about the Internet and health critiqued in sociological
      literature. These metaphorical descriptions characterise SNS content as
      essentially controllable by autonomous users while reiterating existing arguments
      that e-health is both inherently empowering and risky. Our analysis calls for a
      close attention to these understandings of SNSs as they have the potential to
      shape future online initiatives, most notably by anticipating successful
      professional interventions while marginalising the factors that influence users'
      online and offline practices and contexts. 

PMID- 25847535
TI  - Darier-White disease treated with fractional CO2 laser in two cases.
AB  - Darier-White disease is one of the most common genodermatoses. The most typical
      clinical symptoms such as diffuse hyperkeratotic papulae usually appear during
      puberty or early adulthood in seborrhoeic area. It is connected with substantial
      deterioration of the quality of life due to aesthetic defect. Although there
      exist many therapeutic options, the disease still causes considerable therapeutic
      difficulties. Treatment with fractional CO2 laser seems to be a promising
      therapeutic method. In this paper, we present two cases of patients with Darier's
      disease who have been treated with a fractional CO2 laser with very good clinical
      outcome. 

PMID- 25847536
TI  - Failing to forget: inhibitory-control deficits compromise memory suppression in
      posttraumatic stress disorder.
AB  - Most people have experienced distressing events that they would rather forget.
      Although memories of such events become less intrusive with time for the majority
      of people, those with posttraumatic stress disorder (PTSD) are afflicted by
      vivid, recurrent memories of their trauma. Often triggered by reminders in the
      daily environment, these memories can cause severe distress and impairment. We
      propose that difficulties with intrusive memories in PTSD arise in part from a
      deficit in engaging inhibitory control to suppress episodic retrieval. We tested
      this hypothesis by adapting the think/no-think paradigm to investigate voluntary
      memory suppression of aversive scenes cued by naturalistic reminders. Retrieval
      suppression was compromised significantly in PTSD patients, compared with trauma
      exposed control participants. Furthermore, patients with the largest deficits in
      suppression-induced forgetting were also those with the most severe PTSD
      symptoms. These results raise the possibility that prefrontal mechanisms
      supporting inhibitory control over memory are impaired in PTSD. 

PMID- 25847538
TI  - Rac1 functions as a reversible tension modulator to stabilize VE-cadherin trans
      interaction.

PMID- 25847537
TI  - Open source software for quantification of cell migration, protrusions, and
      fluorescence intensities.
AB  - Cell migration is frequently accompanied by changes in cell morphology
      (morphodynamics) on a range of spatial and temporal scales. Despite recent
      advances in imaging techniques, the application of unbiased computational image
      analysis methods for morphodynamic quantification is rare. For example, manual
      analysis using kymographs is still commonplace, often caused by lack of access to
      user-friendly, automated tools. We now describe software designed for the
      automated quantification of cell migration and morphodynamics. Implemented as a
      plug-in for the open-source platform, ImageJ, ADAPT is capable of rapid,
      automated analysis of migration and membrane protrusions, together with
      associated fluorescently labeled proteins, across multiple cells. We demonstrate
      the ability of the software by quantifying variations in cell population
      migration rates on different extracellular matrices. We also show that ADAPT can
      detect and morphologically profile filopodia. Finally, we have used ADAPT to
      compile an unbiased description of a "typical" bleb formed at the plasma membrane
      and quantify the effect of Arp2/3 complex inhibition on bleb retraction. 

PMID- 25847539
TI  - G3BP1 promotes stress-induced RNA granule interactions to preserve polyadenylated
      mRNA.
AB  - G3BP1, a target of TDP-43, is required for normal stress granule (SG) assembly,
      but the functional consequences of failed SG assembly remain unknown. Here, using
      both transformed cell lines and primary neurons, we investigated the functional
      impact of this disruption in SG dynamics. While stress-induced translational
      repression and recruitment of key SG proteins was undisturbed, depletion of G3BP1
      or its upstream regulator TDP-43 disturbed normal interactions between SGs and
      processing bodies (PBs). This was concomitant with decreased SG size, reduced SG
      PB docking, and impaired preservation of polyadenylated mRNA. Reintroduction of
      G3BP1 alone was sufficient to rescue all of these phenotypes, indicating that
      G3BP1 is essential for normal SG-PB interactions and SG function. 

PMID- 25847541
TI  - Epilepsy surgery trends in the United States: Differences between children and
      adults.

PMID- 25847540
TI  - Phosphorylated ubiquitin chain is the genuine Parkin receptor.
AB  - PINK1 selectively recruits Parkin to depolarized mitochondria for quarantine and
      removal of damaged mitochondria via ubiquitylation. Dysfunction of this process
      predisposes development of familial recessive Parkinson's disease. Although
      various models for the recruitment process have been proposed, none of them
      adequately explain the accumulated data, and thus the molecular basis for PINK1
      recruitment of Parkin remains to be fully elucidated. In this study, we show that
      a linear ubiquitin chain of phosphomimetic tetra-ubiquitin(S65D) recruits Parkin
      to energized mitochondria in the absence of PINK1, whereas a wild-type tetra
      ubiquitin chain does not. Under more physiologically relevant conditions, a
      lysosomal phosphorylated polyubiquitin chain recruited phosphomimetic Parkin to
      the lysosome. A cellular ubiquitin replacement system confirmed that ubiquitin
      phosphorylation is indeed essential for Parkin translocation. Furthermore,
      physical interactions between phosphomimetic Parkin and phosphorylated
      polyubiquitin chain were detected by immunoprecipitation from cells and in vitro
      reconstitution using recombinant proteins. We thus propose that the
      phosphorylated ubiquitin chain functions as the genuine Parkin receptor for
      recruitment to depolarized mitochondria. 

PMID- 25847542
TI  - A study on the thermal conversion of scheelite-type ABO4 into perovskite-type
      AB(O,N)3.
AB  - Phase-pure scheelite AMoO4 and AWO4 (A = Ba, Sr, Ca) were thermally treated under
      an ammonia atmosphere at 400 to 900  degrees C. SrMoO4 and SrWO4 were shown to
      convert into cubic perovskite SrMoO2N and SrWO1.5N1.5, at 700  degrees C and 900 
      degrees C respectively, and to form metastable intermediate phases (scheelite
      SrMoO4-xNx and SrWO4-xNx), as revealed by X-ray diffraction (XRD), elemental
      analysis and FTIR spectroscopy. High-temperature oxide melt solution calorimetry
      reveals that the enthalpy of formation for SrM(O,N)3 (M = Mo, W) perovskites is
      less negative than that of the corresponding scheelite oxides, though the
      conversion of the scheelite oxides into perovskite oxynitrides is
      thermodynamically favorable at moderate temperatures. The reaction of BaMO4 with
      ammonia leads to the formation of rhombohedral Ba3M2(O,N)8 and the corresponding
      binary metal nitrides Mo3N2 and W4.6N4; similar behavior was observed for CaMO4,
      which converted upon ammonolysis into individual oxides and nitrides. Thus, BaMO4
      and CaMO4 were shown to not provide access to perovskite oxynitrides. The
      influence of the starting scheelite oxide precursor, the structure distortion and
      the degree of covalency of the B-site-N bond are discussed within the context of
      the formability of perovskite oxynitrides. 

PMID- 25847543
TI  - A radiographic study of estimating age by deciduous mandibular canine and molar
      root resorption.
AB  - BACKGROUND AND AIM: Root resorption of deciduous teeth is an important aspect of
      dental development; however, the accuracy of using root resorption as a method of
      estimating age has not been reported. The aim of this study was to assess the
      accuracy of estimating age from fractions of resorbed root in mandibular
      deciduous canines and molars, using published reference data. METHODS: The sample
      was 940 dental panoramic radiographs of dental patients aged 3-16. Deciduous
      mandibular canine and molar roots were staged into levels of resorption (one
      quarter, one half and three quarters). Reliability of root fractions was assessed
      using 193 duplicate readings and calculated using Kappa. Age was estimated using
      Moorrees et al. (1963), Fanning (1961), and O'Meara and Knott (1967), and the
      difference between dental and chronological ages tested using t-test. Accuracy
      was defined as a difference not significant to zero (P<0.05). RESULTS: Results
      show that assessment of levels of root resorption was excellent (Kappa 0.88
      0.94). Some root fractions of molars estimated age accurately; however, the
      standard deviation was more than 2 years. The average difference between dental
      and chronological ages ranged from 0.12 to -2.04 years with standard deviation
      values up to 2 years and the most accurate method was O'Meara and Knott (1967).
      CONCLUSION: Fractions of deciduous root resorption can help to predict age.

PMID- 25847544
TI  - Are qualitative and quantitative sleep problems associated with delinquency when
      controlling for psychopathic features and parental supervision?
AB  - The aim of this study was to explore the relationship between sleep, including
      both qualitative and quantitative aspects, and delinquent behaviour while
      controlling for psychopathic features of adolescents and parental supervision at
      bedtime. We analysed data from a nationally representative sample of 4855 Finnish
      adolescents (mean age 15.3 years, 51% females). Sleep problems, hours of sleep
      and delinquency were evaluated via self-report. Psychopathic features were
      measured with the Antisocial Process Screening Device - Self-Report. In negative
      binomial regressions, gender and sleep-related variables acted as predictors for
      both property and violent crime after controlling for psychopathic features and
      parental supervision at bedtime. The results suggest that both sleep problems (at
      least three times per week, at least for a year) and an insufficient amount of
      sleep (less than 7 h) are associated with property crime and violent behaviour,
      and the relationship is not explained by gender, degree of parental supervision
      at bedtime or co-occurring psychopathic features. These results suggest that
      sleep difficulties and insufficient amount of sleep are associated with
      delinquent behaviour in adolescents. The significance of addressing sleep-related
      problems, both qualitative and quantitative, among adolescents is thus
      highlighted. Implications for a prevention technique of delinquent behaviour are
      discussed. 

PMID- 25847545
TI  - The four or more medicines (FOMM) support service: results from an evaluation of
      a new community pharmacy service aimed at over-65s.
AB  - OBJECTIVE: Inappropriate prescribing and nonadherence have a significant impact
      on hospital admissions and patient quality of life. The English government has
      identified that community pharmacy could make a significant contribution to
      reducing nonadherence and improving the quality of prescribing, reducing both
      hospital admissions and medicines wastage. The objective of this study is to
      evaluate a community pharmacy service aimed at patients over the age of 65 years
      prescribed four or more medicines. METHODS: Patients were invited to participate
      in the service by the community pharmacy team. The pharmacist held regular
      consultations with the patient and discussed risk of falls, pain management,
      adherence and general health. They also reviewed the patient's medication using
      STOPP/START criteria. Data were analysed for the first 6 months of participation
      in the service. KEY FINDINGS: Six hundred twenty patients were recruited with 441
      (71.1%) completing the 6-month study period. Pharmacists made 142 recommendations
      to prescribers in 110 patients largely centred on potentially inappropriate
      prescribing of NSAIDs, PPIs or duplication of therapy. At follow-up, there was a
      significant decrease in the total number of falls (mean -0.116 (-0.217--0.014))
      experienced and a significant increase in medicine adherence (mean difference in
      Morisky Measure of Adherence Scale-8: 0.513 (0.337-0.689)) and quality of life.
      Cost per quality-adjusted life year estimates ranged from L11 885 to L32 466
      depending on the assumptions made. CONCLUSION: By focussing on patients over the
      age of 65 years with four or more medicines, community pharmacists can improve
      medicine adherence and patient quality of life.

PMID- 25847547
TI  - Functioning and quality of life in hoarding: A systematic review.
AB  - Hoarding, the acquisition and inability to let go of a large number of
      possessions, has been found to be associated with high levels of impairment that
      can compromise functioning and quality of life (QoL). Yet few studies have
      specifically investigated the relationship between hoarding and functioning/QoL.
      The present review aimed to summarize the current status of research on
      functioning and QoL in hoarding as well as identify knowledge gaps in the extant
      literature. We conducted systematic searches in ProQuest, PsycINFO, PubMed and
      ScienceDirect, and identified 37 relevant articles for inclusion. There was much
      evidence to indicate that hoarding has a significant impact on various aspects of
      functioning and that functioning can improve with treatment, though findings on
      the relationship between hoarding and QoL were more tenuous. The limitations of
      previous studies and implications of our findings are discussed. 

PMID- 25847548
TI  - Anxiety sensitivity and subjective social status in relation to anxiety and
      depressive symptoms and disorders among Latinos in primary care.
AB  - The present investigation examined the interactive effects of anxiety sensitivity
      and subjective social status in relation to anxiety and depressive symptoms and
      psychopathology among 143 Latinos (85.7% female; Mage=39.0, SD=10.9; 97.2% used
      Spanish as their first language) who attended a community-based primary
      healthcare clinic. Results indicated that the interaction between anxiety
      sensitivity and subjective social status was significantly associated with number
      of mood and anxiety disorders, panic, social anxiety, and depressive symptoms.
      The form of the significant interactions indicated that individuals reporting co
      occurring higher levels of anxiety sensitivity and lower levels of subjective
      social status evidenced the greatest levels of psychopathology and panic, social
      anxiety, and depressive symptoms. The present findings suggest that there is
      merit in focusing further scientific attention on the interplay between anxiety
      sensitivity and subjective social status in regard to understanding, and thus,
      better intervening to reduce anxiety/depressive vulnerability among Latinos in
      primary care. 

PMID- 25847550
TI  - Harvesting the benefits of clinical case reports: how to separate the chaff from
      the wheat?

PMID- 25847549
TI  - Does every transcript originate from a gene?
AB  - Outdated gene definitions favored regions corresponding to mature messenger RNAs,
      in particular, the open reading frame. In eukaryotes, the intergenic space was
      widely regarded nonfunctional and devoid of RNA transcription. Original concepts
      were based on the assumption that RNA expression was restricted to known protein
      coding genes and a few so-called structural RNA genes, such as ribosomal RNAs or
      transfer RNAs. With the discovery of introns and, more recently, sensitive
      techniques for monitoring genome-wide transcription, this view had to be
      substantially modified. Tiling microarrays and RNA deep sequencing revealed
      myriads of transcripts, which cover almost entire genomes. The tremendous
      complexity of non-protein-coding RNA transcription has to be integrated into
      novel gene definitions. Despite an ever-growing list of functional RNAs,
      questions concerning the mass of identified transcripts are under dispute. Here,
      we examined genome-wide transcription from various angles, including evolutionary
      considerations, and suggest, in analogy to novel alternative splice variants that
      do not persist, that the vast majority of transcripts represent raw material for
      potential, albeit rare, exaptation events.

PMID- 25847551
TI  - Towards improving the reporting quality of clinical case reports in complementary
      medicine: assessing and illustrating the need for guideline development.
AB  - BACKGROUND: Case reports have had a varying level of recognition as a source of
      evidence throughout the history of medicine. In recent years, there has been a
      revival of interest in clinical case reports in both conventional and
      complementary medicine. There is a need to further improve the reporting quality
      of clinical case reports of different Complementary and Alternative Medicine
      (CAM) therapies. OBJECTIVES: To provide an overview of the different objectives
      for clinical case reports, identify those that are most relevant for CAM, and to
      develop a conceptual framework for purpose orientated clinical case reporting
      guidelines for CAM therapies. To practically illustrate the chosen approach by
      developing a clinical case reporting guideline for homeopathic cases. METHODS:
      The various objectives of clinical case reports were described by Prof. Milos
      Jenicek, and the potential relevance of these objectives for CAM were discussed
      and graded by a mixed panel of experts. A conceptual framework for developing
      clinical case reporting guidelines for CAM treatments with specific objectives is
      proposed. The aim is to integrate both 'generic' and 'CAM therapy specific'
      quality items. This framework has been practically applied to the development of
      a reporting guideline for clinical case reports in homoeopathy which will be
      reported in a second article. RESULTS: An overview is given of the clinical case
      reporting literature. The conceptual framework for the development of purpose
      orientated CAM clinical case reporting guidelines is presented. This framework is
      based on alignment with the recently published 'generic' CARE guideline for
      reporting of clinical case reports, whilst addressing the CAM specific elements
      at the same time. CONCLUSIONS: The scope and importance of clinical case
      reporting guideline development in CAM is illustrated. A conceptual framework for
      developing CAM specific clinical case reporting guidelines was established. It
      has been implemented using homoeopathy as an illustration, and this will be
      reported in a separate article. Further improvements in clinical case reporting
      in CAM will greatly contribute to CAM research and education, as well as to
      improved patient care.

PMID- 25847552
TI  - Clinical effectiveness of osteopathic treatment in chronic migraine: 3-Armed
      randomized controlled trial.
AB  - OBJECTIVE: To assess the effectiveness of OMT on chronic migraineurs using HIT-6
      questionnaire, drug consumption, days of migraine, pain intensity and functional
      disability. DESIGN: 3-Armed randomized controlled trial setting: all patients
      admitted in the Department of Neurology of Ancona's United Hospitals, Italy, with
      a diagnosis of migraine and without chronic illness, were considered eligible for
      the study. INTERVENTIONS: Patients were randomly divided into three groups: (1)
      OMT+medication therapy, (2) sham+medication therapy and (3) medication therapy
      only. Patients received 8 treatments in a study period of 6 months. MAIN OUTCOME
      MEASURES: Changing from baseline HIT-6 score. RESULTS: 105 subjects were
      included. At the end of the study, ANOVA showed that OMT significantly reduced
      HIT-6 score (mean change scores OMT-conventional care: -8.74; 95% confidence
      interval (CI) -12.96 to -4.52; p<0.001 and OMT-sham: -6.62; 95% CI -10.85 to 
      2.41; p<0.001), drug consumption (OMT-sham: RR=0.22, 95% CI 0.11-0.40; OMT
      control: RR=0.20, 95% CI 0.10-0.36), days of migraine (OMT-conventional care: M=
      21.06; 95% CI -23.19 to -18.92; p<0.001 and OMT-sham: -17.43; 95% CI -19.57 to 
      15.29; p<0.001), pain intensity (OMT-sham: RR=0.42, 95% CI 0.24-0.69; OMT
      control: RR=0.31, 95% CI 0.19-0.49) and functional disability (p<0.001).
      CONCLUSIONS: These findings suggest that OMT may be considered a valid procedure
      for the management of migraineurs. The present trial was registered on
      www.ClinicalTrials.gov (identifier: NCT01851148).

PMID- 25847553
TI  - Evaluation of plant based formulation on adolescent obesity and its associated
      bio-markers: a randomized, double blind, placebo controlled study.
AB  - OBJECTIVE: Obesity and overweight are the fifth most fatal diseases leading to an
      increased rate of morbidity and mortality in global population, with its
      incidence increasing drastically. Taking this into consideration we have
      conducted the present study in order to explore the efficacy of plant based
      formulation in the management of adolescent obesity and its associated
      biomarkers. DESIGN: Randomized, double blind, placebo controlled trial was
      conducted in 130 obese adolescent of both sexes, with BMI above 25kg/m(2). The
      subjects were randomly assigned into test formulation group (TFG) and placebo
      group (PG). TFG received two 500mg capsule containing test formulation whereas,
      the PG received two 500mg of cellulose powder containing capsule daily for 3
      months. The parameters such as blood pressure, inflammatory cytokines, adipokines
      and lipid profile were assessed in all subjects pre and post treatment. RESULTS:
      There was a considerable improvement in the levels of lipid profile, inflammatory
      cytokines, adipokines and blood pressure after treatment in TFG compared to PG.
      The statistical difference obtained between the groups after three months of
      treatment for the various biomarkers are given as mean with 95% CI for BMI (
      1.4+/-0.6 (-2.5 to -0.7)), total cholesterol mg/dl (-20.9+/-5.0 (-30.8 to 
      11.0)), triglyceride mg/dl (-12.9+/-5.7 (-23.9 to -1.2)), HDL-c mg/dl (7.2+/-0.8
      (5.6-8.8)), IL-6 (-0.7+/-0.1 (-0.9 to -0.6)), hs C-reactive protein (CRP) mg/l(
      1.0+/-0.01 (-1.2 to -0.8)), adiponectin ug/ml(4.9+/-0.4 (4.2-5.7)), leptin ng/ml
      (-8.0+/-1.4 (-10.7 to -5.3)), diastolic blood pressure (DBP) mmHg (-10.4+/-0.8 (
      12.0 to -8.7)) and systolic blood pressure (SBP) mmHg (-6.7+/-0.7 (-8.1 to 
      5.3)). Also, there was a statistical significance within group TFG. CONCLUSION:
      The study concludes that the test formulation may prevent the future cardio
      vascular risk incidence in obese adolescents by reducing inflammation,
      overweight, lipid profile and by regulating adipokines. Thus it may help to
      improve the health pattern in obese patients with least side effects.

PMID- 25847554
TI  - Clinical efficacy of the co-administration of Turmeric and Black seeds (Kalongi)
      in metabolic syndrome - a double blind randomized controlled trial - TAK-MetS
      trial.
AB  - OBJECTIVE: To compare the clinical efficacy of Black seeds and Turmeric alone and
      its co-administration in lower doses among patients with metabolic syndrome
      (MetS). DESIGN: Double-blind-randomized-controlled trial. SETTING: Hijrat colony,
      Karachi, Pakistan. INTERVENTION: Apparently healthy males (n=250), who screened
      positive for MetS, were randomized to either Black seeds (1.5g/day), Turmeric
      (2.4g/day), its combination (900mg Black seeds and 1.5g Turmeric/day) or placebo
      for 8 weeks. MAIN OUTCOME MEASURES: body-mass-index (BMI), body-fat-percent
      (BF%), waist-circumference (WC), hip-circumference (HC), blood pressure (BP),
      lipid-profile (cholesterol, HDL-cholesterol, LDL-cholesterol and TG), fasting
      blood glucose (FBG) and c-reactive protein (CRP). RESULTS: At 4 weeks, compared
      to baseline, Black seed and Turmeric alone showed improvement in BMI, WC and BF%.
      Combination improved all parameters except HDL-cholesterol with lower FBG and LDL
      cholesterol as compared to placebo. At 8 weeks, compared to placebo, Black seeds
      reduced lipids and FBG, while Turmeric reduced LDL-cholesterol and CRP.
      Interestingly, combination group with 60% dose of the individual herbs showed an
      improvement in all parameters from baseline. When compared to placebo, it reduced
      BF%, FBG, cholesterol, TG, LDL-cholesterol, CRP and raised HDL-cholesterol.
      CONCLUSION: Turmeric and Black seeds showed improvement in all parameters of
      metabolic syndrome, when co-administered at 60% of doses of individual herbs with
      enhanced efficacy and negligible adverse-effects. The combination of Black seeds
      and Turmeric can therefore, be recommended with lifestyle modification as a
      starting point for patients with MetS to halt its future complications and
      progression.

PMID- 25847555
TI  - Tango for treatment of motor and non-motor manifestations in Parkinson's disease:
      a randomized control study.
AB  - OBJECTIVE: To determine effects of Argentine tango on motor and non-motor
      manifestations of Parkinson's disease. DESIGN: Randomized control trial.
      PARTICIPANTS: Forty patients with idiopathic Parkinson's disease. SETTING:
      Movement disorder clinic and dance studio. INTERVENTION: Two randomized groups:
      group (N=18) with 24 partnered tango classes, and control self-directed exercise
      group (N=15). MAIN OUTCOMES MEASURES: The primary outcome was overall motor
      severity. Secondary outcomes included other motor measures, balance, cognition,
      fatigue, apathy, depression and quality of life. RESULTS: On the primary
      intention-to-treat analysis there was no difference in motor severity between
      groups MDS-UPDRS-3 (1.6 vs.1.2-point reduction, p=0.85). Patient-rated clinical
      global impression of change did not differ (p=0.33), however examiner rating
      improved in favor of tango (p=0.02). Mini-BESTest improved in the tango group
      compared to controls (0.7+/-2.2 vs. -2.7+/-5.9, p=0.032). Among individual items,
      tango improved in both simple TUG time (-1.3+/-1.6s vs. 0.1+/-2.3, p=0.042) and
      TUG Dual Task score (0.4+/-0.9 vs. -0.2+/-0.4, p=0.012), with borderline
      improvement in walk with pivot turns (0.2+/-0.5 vs. -0.1+/-0.5, p=0.066). MoCa
      (0.4+/-1.6 vs. -0.6+/-1.5, p=0.080) and FSS (-3.6+/-10.5 vs. 2.5+/-6.2, p=0.057)
      showed a non-significant trend toward improvement in the tango group. Tango
      participants found the activity more enjoyable (p<0.001) and felt more "overall"
      treatment satisfaction (p<0.001). We found no significant differences in other
      outcomes or adverse events. CONCLUSION: Argentine tango can improve balance, and
      functional mobility, and may have modest benefits upon cognition and fatigue in
      Parkinson's disease. These findings must be confirmed in longer-term trials
      explicitly powered for cognition and fatigue.

PMID- 25847556
TI  - Measuring expectations of benefit from treatment in acupuncture trials: a
      systematic review.
AB  - OBJECTIVES: We conducted a systematic review that aimed to document and describe
      how (1) expectation of benefit from treatment (response expectancies) were
      measured and reported in acupuncture trials, and (2) examine any effect on
      outcomes. DESIGN: We searched MEDLINE, EMBASE, AMED, CIHAHL, CENTRAL and Science
      and Technology Proceedings up to November 2007 for randomised (RCT) and quasi
      randomised (CCT) controlled trials and prospective controlled cohorts of
      acupuncture as treatment for a medical or psychological condition in adults. An
      update citation search was conducted in April 2010. We included studies that
      mentioned soliciting response expectancies. RESULTS: We found 58 RCTs that
      fulfilled our inclusion criteria. Around half referenced one of five published
      instruments, most of which were designed to measure sham credibility and included
      one question on response expectancy. A wide range of question phrasing and
      response scales was used. There was some evidence that response scales may
      influence the measurement of expectations. Eight trials analysed the association
      between pre-randomisation expectations for assigned treatment and outcomes, and
      six the effect of pre-randomisation expectations across all patients independent
      of treatment allocation. Some showed associations but others did not.
      CONCLUSIONS: There is some evidence that response expectancies interact with
      outcomes in acupuncture trials however the variety of question phrasing and
      analysis methods precludes drawing a firm conclusion about for whom and under
      which circumstance. To further our understanding of expectations, more
      methodological work is needed to standardise the questions and response scales
      that are used.

PMID- 25847557
TI  - A randomized controlled trial of auricular acupressure in heart rate variability
      and quality of life for hypertension.
AB  - BACKGROUND: Hypertension is one of the most common chronic diseases. Hypertensive
      patients who intend to control blood pressure need professional medical
      assistance. Auricular acupressure is a patient-dependent task, wherein a person
      does not have to rely on a healthcare professional to self-perform the task.
      OBJECTIVE: To evaluate the effects of auricular acupressure on heart rate
      variability (HRV) and quality of life (QoL) in patients with hypertension.
      METHODS: A randomized controlled trial with permuted block randomization was
      used. In total, 150 participants from a medical teaching hospital were randomly
      assigned to the experimental group that received auricular acupressure for 10
      weeks, and the control group that received only routine care of equal duration.
      Outcomes were assessed through HRV parameters, heart rate, blood pressure, and
      QoL before and after the auricular acupressure intervention. RESULTS: After the
      adjustment of disease duration and mental health, a significant difference
      existed between the two groups in body pain (p=.03) and mental health (p=.002) of
      QoL, but not in HRV parameters, heart rate, blood pressure, and overall QoL
      (p>.05). CONCLUSION: Acupressure can be applied at the acupoints of shenmen,
      sympathesis, kidney, liver, heart, and subcortex to improve physical pain and
      mental health of QoL for hypertensive patients. Auricular acupressure is
      acceptable and feasible although it does not support physiological benefits.
      Further studies are warranted to assure the effects of using auricular
      acupressure as an adjunctive care for patients with hypertension.

PMID- 25847558
TI  - Effects of dance on motor functions, cognitive functions, and mental symptoms of
      Parkinson's disease: a quasi-randomized pilot trial.
AB  - OBJECTIVE: To examine the effectiveness of dance on motor functions, cognitive
      functions, and mental symptoms of Parkinson's disease (PD). DESIGN: This study
      employed a quasi-randomised, between-group design. SETTING: Dance, PD exercise,
      and all assessments were performed in community halls in different regions of
      Japan. PARTICIPANTS: Forty-six mild-moderate PD patients participated.
      INTERVENTION: Six PD patient associations that agreed to participate in the study
      were randomly assigned to a dance group, PD exercise group, or non-intervention
      group. The dance and PD exercise groups performed one 60-min session per week for
      12 weeks. Control group patients continued with their normal lives. All groups
      were assessed before and after the intervention. MAIN OUTCOME MEASURES: We used
      the Timed Up-and-Go Test (TUG) and Berg Balance Scale (BBS) to assess motor
      function, the Frontal Assessment Battery at bedside (FAB) and Mental Rotation
      Task (MRT) to assess cognitive function, and the Apathy Scale (AS) and Self
      rating Depression Scale (SDS) to assess mental symptoms of PD. The Unified
      Parkinson's Disease Rating Scale (UPDRS) was used for general assessment of PD.
      RESULTS: When comparing results before and after intervention, the dance group
      showed a large effect in TUG time (ES=0.65, p=0.006), TUG step number (ES=0.66,
      p=0.005), BBS (ES=0.75, p=0.001), FAB (ES=0.77, p=0.001), MRT response time
      (ES=0.79, p<0.001), AS (ES=0.78, p<0.001), SDS (ES=0.66, p=0.006) and UPDRS
      (ES=0.88, p<0.001). CONCLUSIONS: Dance was effective in improving motor function,
      cognitive function, and mental symptoms in PD patients. General symptoms in PD
      also improved. Dance is an effective method for rehabilitation in PD patients.

PMID- 25847559
TI  - Effects of Ginkgo biloba extract on cerebral oxygen and glucose metabolism in
      elderly patients with pre-existing cerebral ischemia.
AB  - SPECIFIC AIM: Cerebral injury caused by hypoperfusion during the perioperative
      period is one of the main causes of disability and death in patients after major
      surgery. No effective protective or preventative strategies have been identified.
      This study was designed to evaluate the effects of Ginkgo biloba extract on
      cerebral oxygen and glucose metabolism in elderly patients with known, pre
      existing cerebral ischemia. METHODS: Sixty ASA (American Society of
      Anesthesiologists) II-III patients, diagnosed with vertebral artery ischemia by
      transcranial Doppler ultrasonography (TCD), and scheduled for elective total hip
      replacement surgery, were enrolled in the study. They were randomly allocated to
      receive either 1mg/kg Ginkgo biloba extract (G group n=30) or normal saline (D
      group n=30) after induction of anesthesia. Blood samples were collected from
      radial artery and jugular venous bulb catheters for blood gas analysis and
      determination of glucose and lactate concentrations preoperatively, before
      surgical incision, at the end of surgery, and on post-op day 1. Arterial O2
      content (CaO2), jugular venous O2 content (CjvO2), arteriovenous O2 content
      difference (Da-jvO2), cerebral oxygen extraction rate (CEO2), and arteriovenous
      glucose and lactate content differences (Da-jvGlu and Da-jvLac) were calculated.
      RESULTS: There were no significant differences in CaO2 or Da-jvGlu during surgery
      between groups (p>0.05). However, the Ginkgo group had higher CjvO2, internal
      jugular venous oxygen saturation (SjvO2) and lower CEO2, Da-jvO2 and Da-jvLac at
      the end of surgery (T2) and on post-op day 1 (T3) than those in the control group
      (p<0.05). CONCLUSION: Ginkgo biloba extract can improve cerebral oxygen supply,
      decrease cerebral oxygen extraction rate and consumption, and help maintain the
      balance between cerebral oxygen supply and consumption. It has no effect,
      however, on cerebral glucose metabolism in elderly patients with known, pre
      existing cerebral ischemia.

PMID- 25847560
TI  - Efficacy of adjuvant Chinese herbal formula treatment for chronic tinnitus: a
      retrospective observational study.
AB  - BACKGROUND: The aim of this study was to evaluate the clinical efficacy of using
      western anti-tinnitus therapy with or without Chai-Hu-Jia-Long-Gu-Mu-Li-Tang
      (CHJLGMLT) to treat patients with chronic tinnitus. METHODS: A descriptive case
      series with chart review was established to compare patients with chronic
      tinnitus who had received CHJLGMLT with western anti-tinnitus therapy (the
      CHJLGMIT group) with those who received western anti-tinnitus therapy alone (the
      non-CHJLGMIT group). We included 21 patients, 10 patients in the CHJLGMIT group
      with CHJLGMLT and 11 patients in the non-CHJLGMIT group. Both groups were
      comparable in terms of patient demographics and clinical characteristics. The
      follow-up examinations included the assessment of Tinnitus Handicap Inventory
      (THI), Pittsburgh Sleep Quality Index (PSQI), Visual Analogue Scale (VAS) of 0-10
      for tinnitus intensity, pure tone audiometry (PTA), and speech reception
      threshold (SRT). RESULTS: After 2 months of treatment, THI and PSQI scores were
      reduced significantly more in the CHJLGMIT group (p<0.05) than in the non
      CHJLGMIT group. Scores on the emotional subscale of the THI were significantly
      reduced in the CHJLGMIT group (p<0.05) after treatment, but the effects on the
      seven PSQI subscales did not differ significantly between the two groups
      (p>0.05). Scores on the VAS for tinnitus loudness were significantly reduced in
      both groups (p<0.05). No significant differences between the two groups were
      found on the binaural hearing tests (PTA and SRT). CONCLUSIONS: Our study found
      that adjuvant CHJLGMLT therapy for chronic tinnitus may exert additional efficacy
      by improving psychological sensation of tinnitus and sleep quality. Future
      randomized controlled double-blind studies should be performed to elucidate its
      efficacy.

PMID- 25847561
TI  - Effects of symptoms and complementary and alternative medicine use on the yang
      deficiency pattern among breast cancer patients receiving chemotherapy.
AB  - BACKGROUND: Based on traditional Chinese medicine (TCM) theory, yang deficiency
      pattern defined as an insufficiency of meridian energy (qi) is related to
      worsening disease symptoms. However, there is a lack of studies portraying the
      relationship among complementary and alternative medicine (CAM) use, symptoms,
      and meridian energy. Therefore, the primary purpose of this study was to describe
      the changes of CAM use, symptoms, and yang deficiency pattern among patients with
      breast cancer receiving chemotherapy. Additionally, the study explored factors
      predicting yang deficiency pattern. METHOD: A longitudinal study was performed
      with 153 women with breast cancer at four teaching hospitals in northern Taiwan
      from June 1, 2009 to July 31, 2013. Researchers collected data before treatment
      and the 1st and 3rd months after chemotherapy. Yang deficiency pattern was
      examined using the Meridian Energy Analysis Device Me-Pro. Symptom severity and
      interference were assessed using the MD Anderson Symptom Inventory-Taiwan
      version. CAM use was evaluated using the US National Center for Complementary and
      Alternative Medicine (NCCAM) classification. RESULTS: Meridian energy remained
      essentially the same over the 3-month period as the difference was not
      statistically significant. As time went by, patients developed worsening symptom
      severity and interference. More than 66% of the patients used CAM during
      chemotherapy. Older women had lower overall meridian energy. The more severe the
      symptoms were, the lower the overall meridian energy was. The patients who used
      tai chi or qi gong had higher overall meridian energy and those who used prayer
      or spirituality had lower overall meridian energy. CONCLUSION AND IMPLICATIONS:
      Symptom severity and interference among patients deteriorated during
      chemotherapy. Health providers should observe symptom changes and improve yang
      deficiency pattern. Whether or not use of CAM practices such as tai chi or qi
      gong improves the overall health of breast cancer patients on chemotherapy is
      worth further study.

PMID- 25847562
TI  - Communication of professional literature amongst European Acupuncturists
      affiliated to the ETCMA (European Traditional Chinese Medicine Association):
      explorative survey amongst Traditional Chinese Medicine practitioners in Europe.
AB  - OBJECTIVES: The primary aim of the survey was to explore the information needs
      and information seeking behavior amongst the ETCMA members concerning
      professional literature (scientific as well as practical background knowledge).
      METHODS: A web-based survey comprising of 18 questions with a total of 25 items
      was carried out in 15 affiliated associations in 14 countries in June 2012. The
      survey consisted out of 4 parts: (1) Demographics, (2) Level of interest in and
      availability of professional literature, (3) Insight, needs and opinions on EBM
      (Evidence Based Medicine), and (4) Awareness of the science workshop at the TCM
      Rothenburg Congress. RESULTS: 2590 (25%) from 10,428 members completed the
      questionnaire, of which 58.8% was female. More than 50% of the respondents from
      eleven out of fourteen countries indicate an interest in more education on
      reading scientific literature. Case studies (range 3.19/4-3.86/4) are preferred
      compared to scientific (range 2.78/4-3.59/4) or philosophical knowledge (range
      3.0/4-3.56/4). Exchange with colleagues (range 2.95/4-3.64/4) is preferred
      compared to deepening knowledge (range 2.57/4-3.05/4) in the theoretical
      spectrum. 61% has no knowledge of the EBM model and base clinical decisions on
      personal experience (range 3.47-3.82) and practical skills (range 3.47-3.74)
      compared to clinical practice guidelines (range 2.6-3.27). CONCLUSIONS: Due to
      heterogeneity in structure and size of the affiliated associations no strict
      conclusions can be made. We can conclude though that TCM practitioners rely
      mostly on practical knowledge and have less tendency toward more scientifically
      oriented models like the EBM model. We find this reflected in information needs
      as well as information seeking behavior patterns.

PMID- 25847563
TI  - A case of chemotherapy-induced congestive heart failure successfully treated with
      Chinese herbal medicine.
AB  - OBJECTIVE: A case is presented to illustrate a potential effect of Chinese herbal
      medicine (CHM) formulas in treating chemotherapy-induced cardiotoxicity. CLINICAL
      PRESENTATION: An 18-year-old adolescent male with refractory acute lymphoblastic
      leukemia (ALL) had experienced anthracycline-induced congestive heart failure
      (CHF) for 3 weeks. Under intensive care with conventional therapy, the patient
      still had exercise intolerance and depended on supplemental oxygen all day.
      Therefore, he consented to treatment with traditional Chinese medicine (TCM) for
      alternative therapy. INTERVENTIONS AND OUTCOMES: This patient was treated with
      modified Zhi Gan Cao Tang (ZGCT), three times a day for 2 months. After 6 days of
      CHM treatment, the patient could tolerate daily activity without supplemental
      oxygen. After 2 months of CHM treatment, the follow-up chest X-ray showed great
      improvements in pulmonary edema and cardiomegaly. CONCLUSIONS: In this case,
      anthracycline-induced cardiotoxicity resolved slowly following the administration
      of modified ZGCT. It is suggested that the CHM formula has a protective effect on
      the progression of CHF secondary to the use of anthracyclines in pediatric
      cancer. Further studies to determine the mechanism and clinical trials are
      warranted.

PMID- 25847564
TI  - Student identification of the need for complementary medicine education in
      Australian medical curricula: a constructivist grounded theory approach.
AB  - OBJECTIVE: Across the Western world, including Australia, growing popularity of
      complementary medicines (CMs) mandates their implementation into medical
      education (ME). Medical students in international contexts have expressed a need
      to learn about CMs. In Australia, little is known about the student-specific need
      for CM education. The objective of this paper was to assess the self-reported
      need for CM education among Australian medical students. DESIGN: Thirty second
      year to final-year medical students participated in semi-structured interviews. A
      constructivist grounded theory methodological approach was used to generate,
      construct and analyse data. SETTING: Medical school education faculties in
      Australian universities. RESULTS: Medical students generally held favourable
      attitudes toward CMs but had knowledge deficits and did not feel adept at
      counselling patients about CMs. All students were supportive of CM education in
      ME, noting its importance in relation to the doctor-patient encounter,
      specifically with regard to interactions with medical management. As future
      practitioners, students recognised the need to be able to effectively communicate
      about CMs and advise patients regarding safe and effective CM use. CONCLUSIONS:
      Australian medical students expressed interest in, and the need for, CM education
      in ME regardless of their opinion of it, and were supportive of evidence-based
      CMs being part of their armamentarium. However, current levels of CM education in
      medical schools do not adequately enable this. This level of receptivity suggests
      the need for CM education with firm recommendations and competencies to assist CM
      education development required. Identifying this need may help medical educators
      to respond more effectively.

PMID- 25847565
TI  - Traditional herbal medicine for cancer pain: a systematic review and meta
      analysis.
AB  - BACKGROUND: The effectiveness of traditional herbal medicine (THM) as an
      adjunctive therapy for cancer pain is unclear. OBJECTIVE: To assess the
      effectiveness of THM as an adjunctive therapy for cancer pain using randomized
      controlled trials (RCTs). METHODS: Five electronic databases, including those
      from the UK and China, were systematically searched for the period before
      September 2013. All RCTs involving the use of THM in combination with
      conventional cancer therapy for cancer pain were included. RESULTS: Twenty-four
      RCTs involving 4889 patients with cancer pain were systematically reviewed. Among
      them, nine studies of 952 patients reported a significant decrease in the number
      of patients with cancer pain in the treatment group. Four studies of 1696
      patients reported a significant decrease in the degree of pain in the treatment
      group. CONCLUSION: The results of these studies suggest that THM combined with
      conventional therapy is efficacious as an adjunctive therapy for patients with
      cancer pain. However, more research, including well-designed, rigorous, and
      larger clinical trials, are necessary to address these issues.

PMID- 25847566
TI  - Effects of black seed (Nigella sativa) on metabolic parameters in diabetes
      mellitus: a systematic review.
AB  - BACKGROUND: Current evidence indicated beneficial effects of some medicinal herbs
      on metabolic parameters. Nigella sativa is an example of herbs which can
      ameliorate metabolic factors in diabetes mellitus. Despite several narrative
      review studies on medicinal properties of NS, it seems that there is no
      systematic review to summarize effects of NS on glucose homoeostasis and lipid
      profile in diabetes mellitus. Therefore, the aim of present study was to review
      effects of N. sativa on metabolic parameters in diabetes mellitus. METHODS:
      Pubmed, Science Direct, Google scholar and Springer databases were searched from
      1995 till January 2014. Key words were included: N. sativa, black seed, diabetes,
      glucose level, lipid and insulin. Searching was limited to articles with English
      language. Review articles, case reports, abstract in symposium and congress,
      studies on N. sativa mixed with other plants were excluded. Based on critically
      appraise, eligibility of included articles were evaluated. RESULTS: Finally 19
      eligible articles (2 human trials, 14 animal models and 3 in vivo/in vitro
      studies) were selected. They indicated that N. sativa can modulate hyperglycemia
      and lipid profile dysfunction with various potential mechanisms including its
      antioxidant characteristics and effects on insulin secretion, glucose absorption,
      gluconeogenesis and gene expression. Some studies compared effects of various
      types (extract, oil, powdered) of N. sativa with each other and they reported
      different characteristics with various types of black seed. CONCLUSION: N. sativa
      can improve glycemic status and lipid profile in diabetes models. However, more
      clinical trials are necessary to clarify beneficial effects of N. sativa, its
      effective type and dosage for diabetes management and its complications.

PMID- 25847567
TI  - Oral Chinese herbal medicine for kidney nourishment in Alzheimer's disease: a
      systematic review of the effect on MMSE index measures and safety.
AB  - OBJECTIVE: To evaluate the effectiveness and safety of the Chinese herbal
      medicine for kidney nourishment (CHMK) assessed with the Mini-Mental Status
      Examination (MMSE) index objective outcome measures in individuals with
      Alzheimer's disease. METHODS: Searches were conducted in 7 medical databases from
      their inceptions until July 19, 2014 for randomized controlled trials (RCTs) that
      compared the oral administration of CHMK plus conventional pharmacotherapy with
      the same conventional pharmacotherapy alone with MMSE index measures as outcomes.
      Relevant resources were also manually retrieved. Two reviewers screened the
      citations of the reports, assessed the risk of bias and extracted data
      independently. Data analysis was carried out with Cochrane Collaboration's
      RevMan5.2.6 software and evidence quality grading evaluation of the systematic
      review was conducted with Grades of Recommendations Assessment Development and
      Evaluation (GRADE) profiler software. RESULTS: A total of 20 studies involving
      1682 participants were included in the meta-analysis. There were 15 trials that
      compared CHMK with conventional pharmacotherapy and 5 trials that compared CHMK
      plus conventional pharmacotherapy with conventional pharmacotherapy alone. The
      main meta-analysis results showed relative benefits in effective rates in five
      studies (odds ratio [OR] 2.74, 95% confidence interval [CI] 1.55-4.85) and cure
      rate/clinical-control rates in five studies (OR 1.91, 95% CI 1.27-2.88) in favor
      of the CHMK plus conventional pharmacotherapy group. As for CHMK compared with
      conventional pharmacotherapy, no significant differences were noted in the
      effective rate (OR 1.09, 95% CI 0.82-1.46; cure rate (OR 1.06, 95% CI 0.81-1.38)
      and detailed sub-group of MMSE scores from the onset time to 4 weeks (weighted
      mean difference [WMD] 0.31, 95% confidence interval [CI] -0.81 to 1.42, 8 weeks
      WMD 1.12, 95% CI -0.54 to 2.78, 12 weeks (WMD 0.43, 95% CI -1.62 to 2.48, or 24
      weeks WMD 1.92, 95% CI -1.60 to 5.44) follow-up and the overall effect (WMD 0.79,
      95% CI -0.11 to 1.69). Moreover, weaknesses in methodological quality were
      identified in most studies according to Cochrane Risk of Bias tool assessment,
      while the quality level of GRADE classification indicated "very low". The
      incidence of adverse events with CHMK (0.87%) was lower than in the conventional
      pharmacotherapy group (4.08%), which revealed use of CHMK was relatively safer
      than conventional pharmacotherapy alone. CONCLUSION: The effectiveness and safety
      of oral administration of CHMK cannot be currently determined because of
      publication bias and the low quality level of the included trials. Further
      studies on a larger scale and with more rigorous designs are required to define
      the role of CHMK in the treatment of AD.

PMID- 25847568
TI  - Wen Dan Decoction for hemorrhagic stroke and ischemic stroke.
AB  - OBJECTIVE: The use of traditional Chinese medicine (TCM) in stroke is increasing
      worldwide. Here we report the existing clinical evidence of the Pinellia Ternata
      containing formula Wen Dan Decoction (WDD) for the treatment of ischemic stroke
      and hemorrhagic stroke. METHODS: PubMed, CNKI, Wan Fang database, Cochrane
      Library and online Clinical Trial Registry were searched up to 26 February 2013
      for randomized, controlled clinical trials (RCTs) using WDD as intervention
      versus Western conventional medicine as control to treat stroke. Clinical
      outcomes were improvement of the Neurological Functional Deficit Scores (NFDS)
      and overall therapeutic efficacy rates including rate of cure. Meta-regression
      analysis using Hedges'g was performed for RCTs with significant heterogeneity.
      RESULTS: A total of 22 RCTs of ischemic stroke and 4 RCTs of hemorrhagic stroke,
      involving 2214 patients (1167 used WDD), met our inclusion criteria. Meta
      analysis of the 13 RCTs reporting NFDS improvement favored WDD over the control
      (mean difference=-3.40, 95% confidence intervals [CI]=[-4.64, -2.15]). Rate of
      overall therapeutic efficacy (odds ratio [OR]=3.39, 95%CI=[1.81, 6.37]) for
      hemorrhagic stroke were significantly higher in WDD treated patients than the
      control subjects. In the 1898 patients with ischemic stroke, WDD medication also
      achieved higher rates of cure (OR=2.22, 95%CI=[1.66, 2.97]) and overall
      therapeutic efficacy (OR=3.31, 95%CI=[2.54, 4.31]) than the conventional
      treatment. CONCLUSIONS: WDD displays benefits on improvement of neurological
      function and overall therapeutic efficacy in post-stroke patients. TCM such as
      WDD may serve as a therapeutic tool of dual actions to explore the common
      mechanisms underlying cerebral hemorrhage and ischemia.

PMID- 25847569
TI  - 'Suspended in a paradox'-patient attitudes to wait-listing for kidney
      transplantation: systematic review and thematic synthesis of qualitative studies.
AB  - Patients on waiting lists for kidney transplantation have higher mortality rates
      and have specific anxieties about their eligibility, process, and outcomes of
      wait-listing. We aimed to describe patient experiences and attitudes to wait
      listing for kidney transplantation. Electronic databases were searched to
      September 2014. Thematic synthesis was used to analyze the findings. From 22
      studies (n = 795 patients), we identified six themes: accepting the only option
      (chance to regain normality, avoiding guilt, impulsive decision-making);
      maintaining hope (determined optimism, appreciating a fortuitous gift, enduring
      for optimal outcomes, trust in clinical judgment); burden of testing (strenuous
      commitment, losing the battle, medical mistrust); permeating vulnerability
      (eligibility enigma, being threatened, angst of timing uncertainty, desperate
      urgency, living in limbo, spiraling doubt and disappointment, residual
      ambivalence); deprived of opportunity (unfairly dismissed, unexpected
      disqualification, self-resignation and acceptance, jealousy, suspicious of
      inequity); and moral guilt (awaiting someone's death, questioning deservingness).
      The waiting list offered hope of restored normality. However, the demands of
      workup, uncertainty about eligibility, and waiting times that exceeded
      expectations impelled patients to disillusionment, despair, and suspicion of
      inequity. Managing patient expectations and ensuring transparency of wait-listing
      and allocation decisions may allay patient disappointment and skepticism, to
      improve patient satisfaction and treatment outcomes.

PMID- 25847570
TI  - Significance of decreased serum interleukin-10 levels in the progression of
      cerebral infarction.
AB  - Anti-inflammatory cytokine and its serological detection may have an important
      role in the process of cardiovascular and cerebrovascular diseases. We
      investigated whether serum interleukin-10 (IL-10) is associated with cerebral
      infarction or not in the general population. Identified comprehensive searching
      was performed covering PubMed, EMBASE, Web of Science, Cochrane Library, CISCOM,
      CINAHL, Google Scholar, China BioMedicine, and China National Knowledge
      Infrastructure databases. Two reviewers extracted data and assessed studies
      independently. Information was extracted separately and classed into Asians and
      Caucasians. Summary standardized mean differences (SMDs) with 95 % confidence
      intervals (CI) were used with the utilization of Z test. Nine studies ranged from
      2003 to 2014 were collected for meta-analysis. Results identified a negative
      association between serum IL-10 levels and cerebral infarction (SMD = 1.80, 95 %
      CI 0.79-2.81, P < 0.001). Country-subgroup analysis showed that low IL-10 level
      may be the main risk factor for cerebral infarction in India (SMD = 1.44, 95 % CI
      1.13-1.75, P < 0.001) and Croatia (SMD = 2.96, 95 % CI 2.48-3.44, P < 0.001). In
      the ethnicity-stratified subgroup analysis, serum IL-10 levels were negatively
      correlated with cerebral infarction in Asians (SMD = 2.52, 95 % CI 0.47-4.57, P =
      0.016), while not in Caucasians (P > 0.05). The lower serum IL-10 concentration
      was significantly associated with an increased likelihood of cerebral infarction
      in this meta-analysis. More prospective studies should be conducted to provide
      stronger evidence justifying the use of IL-10 as new biomarker to identify a
      predisposition toward cerebral infarction. 

PMID- 25847571
TI  - Angiotensins as therapeutic targets beyond heart disease.
AB  - The renin-angiotensin system (RAS) plays a pivotal role in cardiovascular and
      hydro-electrolyte homeostasis. Blockade of the RAS as a therapeutic strategy for
      treating hypertension and related cardiovascular diseases is well established.
      However, actions of the RAS go far beyond the targets initially described. In
      this regard, the recent identification of novel components of the RAS, including
      angiotensin-(1-7) [Ang-(1-7)], Ang-(1-9), and alamandine, have opened new
      possibilities for interfering with the development and manifestations of
      cardiovascular and non-cardiovascular diseases. In this article, we briefly
      review novel targets for angiotensins and its therapeutic implications in diverse
      areas, including cancer, inflammation, and glaucoma. 

PMID- 25847572
TI  - Cost-effectiveness of sofosbuvir for the treatment of chronic hepatitis C
      infected patients.
AB  - The efficacy of treatment for hepatitis C genotype 1 infection has significantly
      improved with the introduction of first-generation protease inhibitors. However,
      there remains a need for effective treatments for patients infected with other
      genotypes, for nonresponders and patients unsuitable for interferon. Sofosbuvir
      is the first nucleotide polymerase inhibitor with pan-genotypic activity.
      Sofosbuvir-based regimens have resulted in >90% sustained virological response
      across treatment-naive genotype 1-6 patients in five phase III clinical trials of
      sofosbuvir administered with ribavirin or pegylated interferon and ribavirin.
      This analysis evaluates the cost-effectiveness of sofosbuvir within the current
      licensed indication, for genotype 1-6 in the UK. A Markov model followed a cohort
      of 10 000 patients over lifetime, with approximately 20% initiating treatment for
      compensated cirrhosis. Sofosbuvir-regimens were compared to telaprevir,
      boceprevir, pegylated interferon and ribavirin, or no treatment. Costs and
      outcomes were discounted at 3.5%. The cost perspective utilized costs applicable
      to the National Health Service in the UK. Sofosbuvir proved to be cost-effective
      in most patient populations with incremental cost-effectiveness ratios (ICERs) at
      L11 836/QALY and L7292/QALY against telaprevir and boceprevir, respectively. In
      genotype 3, sofosbuvir had a weighted ICER of L18 761/QALY. Sofosbuvir-based
      regimens are a cost-effective option for the majority of hepatitis C-infected
      patients in the United Kingdom although the incremental cost-effectiveness varies
      by genotype and regimen. Sofosbuvir and ribavirin is an alternative regimen for
      patients unsuitable for interferon. 

PMID- 25847573
TI  - Interactions of Pt-ttpy with G-Quadruplexes Originating from Promoter Region of
      the c-myc Gene Deciphered by NMR and Gel Electrophoresis Analysis.
AB  - This study provides insights into the interactions of Pt-ttpy, that is, a metallo
      organic heterocycle-comprising platinum(II) complex of terpyridine, and G
      quadruplexes adopted by G-rich DNA from the transcriptional regulatory element of
      the c-myc gene, a well-known attractive target for artificial modulation of
      oncogene expression. A previously noted drug-like potential of Pt-ttpy relies on
      its antiproliferative activity on cancer cells and its increased selectivity for
      G-quadruplex binding attributed to the combination of distinct interacting modes.
      The predominant interaction between the herein used models of a parallel G
      quadruplex exhibiting short propeller-type loops and Pt-ttpy occurs through
      stacking to the outer G-quartets. The presence of adenine versus thymine residue
      at the 5'-end overhanging region allows the coordinative binding of Pt-ttpy to
      the G-quadruplex structure. Interestingly, Pt-ttpy triggers the formation of the
      G-quadruplex even in the absence of cations. Furthermore, NMR-based
      characterisation revealed common structural features of Pt-ttpy-G-quadruplex
      complexes in the presence and absence of cations, which indicate that cations may
      be expelled from the cores of the corresponding structures. 

PMID- 25847574
TI  - Idiopathic Facial Aseptic Granuloma: Review of an Evolving Clinical Entity.
AB  - Idiopathic facial aseptic granuloma (IFAG), originally termed pyodermite froide
      du visage, describes a generally asymptomatic facial nodule presenting in
      childhood with clinical resemblance to pyoderma or cystic, granulomatous, or
      vascular lesions. Clinical understanding is constantly evolving, with recent
      observations indicating that IFAG may represent a subtype of childhood rosacea.
      We present a case of IFAG associated with eyelid chalazions in a 19-month-old
      boy. Although his clinical course paralleled previously reported IFAG cases, we
      observed a unique ultrasound variation during initial diagnostic examination.
      Further delineation of clinical, imaging, and histologic properties of IFAG may
      reveal insights into etiologic associations and ideal management. 

PMID- 25847575
TI  - Mutations in ANO3 and GNAL gene in thirty-three isolated dystonia families.

PMID- 25847576
TI  - Effects and mechanism of ultrasound pretreatment on rapeseed protein enzymolysis.
AB  - BACKGROUND: The disadvantages which stem from the use of traditional enzymolysis
      of protein has necessitated the need to employ sweeping frequency and pulsed
      ultrasound (SFPU) in the pretreatment of rapeseed protein prior to proteolysis in
      order to bring about improvement in enzymolysis efficiency. Further, in order to
      determine the mechanism of ultrasound-accelerated enzymolysis of RP, the effects
      of SFPU on the kinetics, thermodynamics, molecular conformation and
      microstructure of RP were investigated. RESULTS: Kinetic studies showed that SFPU
      pretreatment on RP improved enzymolysis by decreasing the apparent constant KM
      significantly (P < 0.05) by 32.8% and reducing the thermodynamic parameters Ea ,
      DeltaH and DeltaS by 16.6%, 17.7% and 9.2% respectively. Fluorescence spectra
      revealed that SFPU pretreatment induced molecular unfolding, causing more
      hydrophobic groups and regions inside the molecules to be exposed to the outside.
      Circular dichroism analysis indicated that SFPU pretreatment decreased the alpha
      helix content by 16.1% and increased the random coil content by 3.6%. In
      addition, scanning electron microscopy showed that SFPU pretreatment increased
      the specific surface area of RP. CONCLUSION: Ultrasound pretreatment is an
      efficient method in RP proteolysis to produce peptides through its impact on the
      molecular conformation and microstructure of proteins.

PMID- 25847577
TI  - Retaining traditionally hard to reach participants: Lessons learned from three
      childhood obesity studies.
AB  - Retaining underserved populations, particularly low-income and/or minority
      participants in research trials, presents a unique set of challenges. In this
      paper, we describe the initial retention strategies and enhanced the retention
      strategies over time across three childhood obesity prevention trials. Hip-Hop to
      Health Jr. (HH) was a randomized controlled trial (RCT) testing a preschool-based
      obesity prevention intervention among predominately African-American children.
      Retention was 89% at 14-weeks, 71% at 1-year, and 73% at 2-year follow-up.
      Primary retention strategies for HH included: 1) collaboration with a community
      based organization to enhance program credibility; 2) continuity of data
      collection locations; 3) collecting detailed contact information and provision of
      monetary compensation; and 4) developing a detailed tracking/search protocol. In
      a follow-up trial, Hip-Hop to Health Jr. Obesity Prevention Effectiveness Trial
      (HH Effectiveness), 95% of participants completed assessment at 14 weeks and 88%
      completed assessment at 1 year. For this trial, we emphasized staffing continuity
      in order to enhance participant relationship building and required data
      collection staff to have relevant community service experience. In a third study,
      we assessed dietary quality among participants in the Special Supplemental
      Nutrition Program for Women, Infants, and Children (WIC) across three time points
      following the WIC food package shift instituted nationally in 2009. Retention
      rates were 91% at 12 months and 89% at 18 months. For our WIC? study, we
      augmented retention by developing a home data collection protocol and increased
      focus on staff diversity training. We conclude with a summary of key strategies
      and suggestions for future research.

PMID- 25847578
TI  - Telephone-adapted mindfulness-based stress reduction (tMBSR) for patients
      awaiting kidney transplantation: Trial design, rationale and feasibility.
AB  - BACKGROUND: Mindfulness-based stress reduction (MBSR) has demonstrated benefits
      for stress-related symptoms; however, for patients with burdensome treatment
      regimens, multiple co-morbidities and mobility impairment, time and travel
      requirements pose barriers to MBSR training. PURPOSE: To describe the design,
      rationale and feasibility results of Journeys to Wellness, a clinical trial of
      mindfulness training delivered in a novel workshop and teleconference format. The
      trial aim is to reduce symptoms and improve quality of life in people waiting for
      a kidney transplant. METHODS: The standard 8-week MBSR program was reconfigured
      for delivery as two in-person workshops separated in time by six weekly
      teleconferences (tMBSR). A time and attention comparison condition (tSupport) was
      created using the workshop-telephone format. FEASIBILITY RESULTS: Kidney
      transplant candidates (N = 63) were randomly assigned to tMBSR or tSupport: 87%
      (n = 55) attended >= 1 class, and for these, attendance was high (6.6 +/- 1.8
      tMBSR and 7.0 +/- 1.4 tSupport sessions). Fidelity monitoring found that all
      treatment elements were delivered as planned and few technical problems occurred.
      Patients in both groups reported high treatment satisfaction, but more tMBSR
      (83%) than tSupport (43%) participants expected their intervention to be quite a
      bit or extremely useful for managing their health. Symptoms and quality of life
      outcomes collected before (baseline, 8 weeks and 6 months) and after kidney
      transplantation (2, 6 and 12 months) will be analyzed for efficacy. CONCLUSIONS:
      tMBSR is an accessible intervention that may be useful to people with a wide
      spectrum of health conditions. Clinicaltrials.gov: NCT01254214.

PMID- 25847579
TI  - Use of mobile devices and the internet for multimedia informed consent delivery
      and data entry in a pediatric asthma trial: Study design and rationale.
AB  - INTRODUCTION: Phase III/IV clinical trials are expensive and time consuming and
      often suffer from poor enrollment and retention rates. Pediatric trials are
      particularly difficult because scheduling around the parent, participant and
      potentially other sibling schedules can be burdensome. We are evaluating using
      the internet and mobile devices to conduct the consent process and study visits
      in a streamlined pediatric asthma trial. Our hypothesis is that these study
      processes will be non-inferior and will be less expensive compared to a
      traditional pediatric asthma trial. MATERIALS/METHODS: Parents and participants,
      aged 12 through 17 years, complete the informed consent process by viewing a
      multi-media website containing a consent video and study material in the
      streamlined trial. Participants are provided an iPad with WiFi and EasyOne
      spirometer for use during FaceTime visits and online twice daily symptom
      reporting during an 8-week run-in followed by a 12-week study period. Outcomes
      are compared with participants completing a similarly designed traditional trial
      comparing the same treatments within the same pediatric health-system. After 8
      weeks of open-label Advair 250/50 twice daily, participants in both trial types
      are randomized to Advair 250/50, Flovent 250, or Advair 100/50 given 1 inhalation
      twice daily. Study staff track time spent to determine study costs. RESULTS:
      Participants have been enrolled in the streamlined and traditional trials and
      recruitment is ongoing. CONCLUSIONS: This project will provide important
      information on both clinical and economic outcomes for a novel method of
      conducting clinical trials. The results will be broadly applicable to trials of
      other diseases.

PMID- 25847580
TI  - Helicobacter pylori with the Intact dupA Cluster is more Virulent than the
      Strains with the Incomplete dupA Cluster.
AB  - The duodenal ulcer promoting gene (dupA), located in the plasticity region of
      Helicobacter pylori (H. pylori), is predicted to form a type IV secretory system
      (T4SS) with vir genes around dupA. In the study, we investigated the association
      between the dupA cluster status and the virulence of H. pylori in a littoral
      region of Northeast China. Two hundred and sixty-two H. pylori strains isolated
      from the chronic gastritis were examined to evaluate the dupA cluster status, cag
      PAI genes and vacA genotype using PCR and Western blot. Histopathologic
      evaluations of biopsy specimens were performed to analysis the association
      between the dupA cluster and the inflammatory response. IL-8 productions in
      gastric mucosa and from GES-1 cells co-cultured with H. pylori were measured,
      respectively, to analysis the association between the dupA cluster status and IL
      8 production. We found that gastric mucosal inflammatory cell infiltration was
      significantly higher in patients with dupA-positive H. pylori, including H.
      pylori with complete dupA cluster (2.71 +/- 0.79) and incomplete dupA cluster
      (2.09 +/- 0.61) than in patients with dupA-negative strain (1.73 +/- 0.60, p <
      0.01), whereas no significant difference in the gastric mucosal atrophy was found
      according to the status of dupA cluster. Gastric mucosal IL-8 levels were higher
      in the complete dupA cluster group than in other groups (p < 0.01), and IL-8
      production from GES-1 cells was also significantly higher in strains with a
      complete dupA cluster (1527.9 +/- 180.0 pg/ml) than in those with an incomplete
      dupA cluster (1229.4 +/- 75.3 pg/ml, p < 0.01) or those with dupA negative
      (1201.9 +/- 92.3 pg/ml, p < 0.01). In conclusion, the complete dupA cluster in H.
      pylori is associated with inflammatory cell infiltration and IL-8 secretion, and
      H. pylori strain with a complete dupA cluster seems to be more virulent than
      other strains with the incomplete dupA cluster or dupA negative. 

PMID- 25847582
TI  - Seduced by technology?

PMID- 25847581
TI  - ELP2 is a novel gene implicated in neurodevelopmental disabilities.
AB  - Elongator is a multi-subunit protein complex essential to transcription
      elongation, histone acetylation, and tRNA modification. The complex consists of
      six highly conserved protein subunits, called Elongator Proteins (ELP) 1-6. Apart
      from an association with intellectual disability (ID), there is limited clinical
      information about patients with ELP2 variants. Here we report on two brothers
      with severe ID, spastic diplegia, and self-injury whose presentation eluded a
      diagnosis for over 20 years. In both brothers, whole exome sequencing revealed a
      likely pathogenic, compound heterozygous missense variant in ELP2. We describe
      the phenotype and natural history of the ELP2-related disorder in these brothers.

PMID- 25847584
TI  - Nitroxide-Mediated Polymerization of Methacrylic Esters: Insights and Solutions
      to a Long-Standing Problem.
AB  - Nitroxide-mediated polymerization (NMP) is one of the most powerful reversible
      deactivation radical polymerization techniques and has incredibly gained in
      maturity and robustness over the last decades. However, control of methacrylic
      esters is one of the different aspects of NMP that still requires improvement.
      This family of monomers always represented an important challenge for NMP,
      despite the many different nitroxide structures that have been designed over the
      course of time. This Review aims to present the most successful strategies
      directed toward the control of the NMP technique of methacrylic esters and
      especially methyl methacrylate. NMP-derived materials comprising uncontrolled
      methacrylate segments will also be discussed. 

PMID- 25847583
TI  - Isolation, identification, and characterization of the nematophagous fungus
      Monacrosporium salinum from China.
AB  - Nematophagous fungi are considered to have the best potential as biological
      agents for the control of gastrointestinal nematodes in domestic animals.
      However, relatively few studies have been conducted with the genus
      Monacrosporium, especially with strains native to China. In the present study, we
      isolated and identified nematophagous fungi from fresh sheep feces. A pure fungal
      strain was molecularly characterized, and its nematophagous activity was
      evaluated. The morphological plasticity of the isolated strain, as well as its
      interaction with the nematode targets, was observed by scanning electron
      microscopy of the infected Trichostrongylus colubriformis L3 and the free-living
      nematode Caenorhabditis elegans. Three isolated fungal strains from the 30 fresh
      fecal samples of sheep from Inner Mongolia, China exhibited predatory activity;
      however, only a single strain was successfully purified (SF 0459). The SF 0459
      strain was characterized by morphological analysis of its conidia and sequencing
      of its ITS1-5.8S rDNA-ITS2 region. This strain was identified to be
      Monacrosporium salinum (GenBank ID: KP036623). Nematophagous fungus helper
      bacteria were found at the interaction points between fungi and nematodes. The
      percentage of live T. colubriformis L3 was reduced by 83.79-88.69% based on the
      in vitro assay. 

PMID- 25847585
TI  - Alternatively spliced products lacking exon 12 dominate the expression of fragile
      X mental retardation 1 gene in human tissues.
AB  - Fragile X mental retardation 1 gene (FMR1) expression is associated with fragile
      X syndrome (FXS) and exhibits several splicing products. However, the proportion
      of spliced isoforms that are expressed in different tissues remains unclear. In
      the present study, long-chain reverse transcription-polymerase chain reaction
      with a T cloning-sequencing method was conducted in order to analyze the entire
      coding region of the FMR1 gene in human tissues. In particular, FXS-associated
      tissues were analyzed, including the brain and testis. Twenty alternatively
      spliced isoforms were observed among 271 recombinants, including six novel ones.
      The isoform that consisted of the entire FMR1 coding region (ISO1) accounted for
      a small proportion of all isoforms. Isoforms lacking exon 12 were the most
      abundant. In particular, spliced isoforms ISO7 and ISO17 were the most abundant.
      However, their relative abundance varied between the peripheral blood cells, and
      the testis and brain tissues. Bioinformatic analyses suggested that exon 12 may
      be the sole exon undergoing positive selection. The results of the present study
      suggested that the mechanisms underlying alternative splicing (AS) of the FMR1
      gene may be more complex. Furthermore, the functions of alternatively spliced
      products lacking exon 12 require further investigation. The results of the
      present study provide novel insights into the association between AS and the
      structure and function of the FMR1 gene.

PMID- 25847588
TI  - Expression of sexual ornaments in a polymorphic species: phenotypic variation in
      response to environmental risk.
AB  - Secondary sexual traits may evolve under the antagonistic context of sexual and
      natural selection. In some polymorphic species, these traits are only expressed
      during the breeding period and are differently expressed in alternative
      phenotypes. However, it is unknown whether such phenotypes exhibit phenotypic
      plasticity of seasonal ornamentations in response to environmental pressures such
      as in the presence of fish (predation risk). This is an important question to
      understand the evolution of polyphenisms. We used facultative paedomorphosis in
      newts as a model system because it involves the coexistence of paedomorphs that
      retain gills in the adult stage with metamorphs that have undergone
      metamorphosis, but also because newts exhibit seasonal sexual traits. Our aim was
      therefore to determine the influence of fish on the development of seasonal
      ornamentation in the two phenotypes of the palmate newt (Lissotriton helveticus).
      During the entire newt breeding period, we assessed the importance of phenotype
      and fish presence with an information-theoretic approach. Our results showed that
      paedomorphs presented much less developed ornamentation than metamorphs and those
      ornamentations varied over time. Fish inhibited the development of sexual traits
      but differently between phenotypes: in contrast to metamorphs, paedomorphs lack
      the phenotypic plasticity of sexual traits to environmental risk. This study
      points out that internal and external parameters act in complex ways in the
      expression of seasonal sexual ornamentations and that similar environmental
      pressure can induce a contrasted evolution in alternative phenotypes.

PMID- 25847589
TI  - PTSD and Sexual Dysfunction in Men and Women.
AB  - INTRODUCTION: Difficulties in sexual desire and function often occur in persons
      with posttraumatic stress disorder (PTSD), but many questions remain regarding
      the mechanisms underlying the occurrence of sexual problems in PTSD. AIM: The aim
      of this review was to present a model of sexual dysfunction in PTSD underpinned
      by an inability to regulate and redirect the physiological arousal needed for
      healthy sexual function away from aversive hyperarousal and intrusive memories.
      METHOD: A literature review pertaining to PTSD and sexual function was conducted.
      Evidence for the comorbidity of sexual dysfunction and PTSD is presented, and
      biological and psychological mechanisms that may underlie this co-occurrence are
      proposed. MAIN OUTCOME MEASURES: This manuscript presents evidence of sexual
      dysfunction in conjunction with PTSD, and of the neurobiology and
      neuroendocrinology of PTSD and sexual function. RESULTS: Sexual dysfunction
      following trauma exposure may be mediated by PTSD-related biological, cognitive,
      and affective processes. CONCLUSIONS: The treatment of PTSD must include
      attention to sexual dysfunction and vice versa.

PMID- 25847590
TI  - Misidentifying a tennis racket as keys: object identification in people with age
      related macular degeneration.
AB  - PURPOSE: Previous studies showed that people with age-related macular
      degeneration (AMD) can categorise a pre-defined target object or scene with high
      accuracy (above 80%). In these studies participants were asked to detect the
      target (e.g. an animal) in serial visual presentation. People with AMD must rely
      on peripheral vision which is more adapted to the low resolution required for
      detection than for the higher resolution required to identify a specific
      exemplar. We investigated the ability of people with central vision loss to
      identify photographs of objects and scenes. METHODS: Photographs of isolated
      objects, natural scenes and objects in scenes were centrally displayed for 2 s
      each. Participants were asked to name the stimuli. We measured accuracy and
      naming times in 20 patients with AMD, 15 age-matched and 12 young controls.
      RESULTS: Accuracy was lower (by about 30%) and naming times were longer (by about
      300 ms) in people with AMD than in age-matched controls in the three categories
      of images. Correct identification occurred in 62-66% of the stimuli for patients.
      More than 20% of the misidentifications resulted from a structural and/or
      semantic similarity between the object and the name (e.g. spectacles for dog
      plates or dolphin for shark). Accuracy and naming times did not differ
      significantly between young and older normally sighted participants indicating
      that the deficits resulted from pathology rather than to normal ageing.
      CONCLUSIONS: These results show that, in contrast to performance for
      categorisation of a single pre-defined target, people with central vision loss
      are impaired at identifying various objects and scenes. The decrease in accuracy
      and the increase in response times in patients with AMD indicate that peripheral
      vision might be sufficient for object and scene categorisation but not for
      precise scene or object identification.

PMID- 25847596
TI  - Odor fingerprinting of Listeria monocytogenes recognized by SPME-GC-MS and E
      nose.
AB  - Microorganisms can produce species-specific microbial volatile organic compounds
      (MVOCs), or odor compounds, which can be characterized by odor fingerprinting.
      The objective of this study was to characterize the odor fingerprint of Listeria
      monocytogenes. Solid-phase microextraction-gas chromatography-mass spectrometry
      (SPME-GC-MS) and electronic nose (E-nose) were used to recognize the MVOCs of L.
      monocytogenes in pure culture medium. The main MVOCs of L. monocytogenes were
      identified by SPME-GC-MS analysis as alcohols, aldehydes, ketones, alkanes, and
      heterocyclics, among which the relative peak area of one compound, 3-hydroxy-2
      butanone, increased along with the growth of L. monocytogenes. The odor
      fingerprint of L. monocytogenes at different growth stages could be clearly
      discriminated by E-nose. In addition, E-nose signals had a very good linear
      relationship with the concentration of this bacterium (R(2) = 0.9937). Our study
      may help to establish the analysis of the odor fingerprint of microorganisms as a
      potential routine method in microbiology.

PMID- 25847597
TI  - Stearidonic acid, a plant-based dietary fatty acid, enhances the chemosensitivity
      of canine lymphoid tumor cells.
AB  - Lymphoma is the most common hematopoietic tumor in dogs and humans, with similar
      pathogenesis and therapeutic responses. Anticancer drugs like vincristine (VCR)
      and doxorubicin (DOX) are often used in treating lymphoma. However, the cure rate
      is generally poor due to chemoresistance. Here, we sought to determine whether
      stearidonic acid (SDA), a plant-based dietary fatty acid, sensitizes
      chemoresistant canine lymphoid-tumor cells. GL-1 B-cell lymphoid-tumor cells were
      found to be highly sensitive to the antitumor-activity of VCR and DOX, while OSW
      T-cell and 17-71 B-cell lymphoid-tumor cells were moderately and fully resistant,
      respectively. SDA, at its non-toxic concentrations, significantly promoted the
      antitumor action of VCR and DOX in both OSW and 17-71 cells. SDA-mediated
      chemosensitization was associated with SDA inhibition of P-glycoprotein (P-gp)
      function. This was confirmed in HEK293 cells stably expressing P-gp as well as by
      increased binding-affinity of SDA to P-gp in P-gp docking analysis. SDA at its
      chemosensitizing concentrations did not affect the viability of healthy dog
      peripheral blood mononuclear cells, suggesting that SDA is non-toxic to normal
      dog peripheral blood leucocytes at its chemosensitizing concentrations. Our study
      identifies a novel dietary fatty acid that may be used as a dietary supplement in
      combination with chemotherapy to promote the antitumor efficacy of the
      chemotherapy drugs in dogs and possibly in humans with chemoresistant lymphoma. 

PMID- 25847598
TI  - The role of Cas-L/NEDD9 as a regulator of collagen-induced arthritis in a murine
      model.
AB  - Cas-L/NEDD9 is a cytoplasmic docking protein downstream of beta1 integrin
      mediated signaling pathway and is essential for cellular migration and beta1
      integrin-mediated costimulation of T cells. We previously found that increased
      number of Cas-L positive leukocytes migrated into the inflamed joints of HTLV-I
      tax transgenic mice which spontaneously develop polyarthritis, suggesting a role
      of Cas-L in rheumatoid arthritis (RA) pathophysiology. Our current study expanded
      these findings on the role of Cas-L/NEDD9 in the development of RA by analyzing
      the pathophysiological changes in a Nedd9(-/-) mouse collagen-induced arthritis
      (CIA) model. Nedd9(-/-) mice exhibited a decrease in arthritis severity as
      compared to Nedd9(+/+) mice. In addition, as being conducted bone marrow
      transplantation experiments with a CIA model, Nedd9(-/-)->Nedd9(+/+) transplant
      showed a decrease in the incidence and severity score of arthritis, compared to
      those of Nedd9(+/+)->Nedd9(-/-) transplant. For analysis of serum levels of
      various cytokines, IL-1beta, IL-6, IL-17, TNF-alpha, IFN-gamma and anti-collagen
      antibody were decreased, while IL-4 and IL-10 levels were increased, in Nedd9(-/
      ) mice as compared to those in Nedd9(+/+) mice. Furthermore, collagen-mediated
      cellular responses of lymphocytes isolated from spleen or affected lymph nodes of
      Nedd9(-/-) mice were reduced. Our results strongly suggest that Cas-L/NEDD9 plays
      a pivotal role in the pathophysiology of CIA, and that Cas-L/NEDD9 may be a
      potential molecular target for the treatment of RA. 

PMID- 25847599
TI  - Proliferation and osteogenic response of MC3T3-E1 pre-osteoblastic cells on
      porous zirconia ceramics stabilized with magnesia or yttria.
AB  - Dense zirconia ceramics are used in bone applications due to their mechanical
      strength and biocompatibility, but lack osseointegration. A porous interface in
      contact with bone tissue may lead to better bone bonding but the biological
      properties of porous zirconia are not widely explored. The present study focuses
      on the manufacturing of an yttria- (YSZ) and a magnesia-stabilized (MgSZ) porous
      zirconia, and on their in vitro biological investigation. The sintered ceramics
      had similar characteristics of porosity, pore size and interconnectivity. Their
      elastic moduli and compressive strength values were within the range of the
      values of human cortical bone. MC3T3-E1 pre-osteoblasts were used to investigate
      the proliferation, alkaline phosphatase (ALP) activity, collagen deposition and
      expression profile of four genes involved in bone metabolism of cells on porous
      ceramics. Scanning electron and fluorescence microscopy were employed to
      visualize cell morphology and growth. Pre-osteoblasts adhered well on both
      ceramics but cell numbers on YSZ were higher. Cells exhibited an increase in ALP
      activity and collagen deposition after 14 days on both MgSZ and YSZ, with higher
      levels on YSZ. Real-time quantitative polymerase chain reaction (qPCR) showed
      that the expression of bone sialoprotein (Bsp) and collagen type I (col1aI) were
      significantly higher on YSZ. No significant differences were found in their
      ability to regulate the early gene expression of Runx2 and Alp. Nevertheless, the
      biomineralized calcium content was similar on both ceramics after 21 days,
      indicating that despite chemical differences, both scaffolds direct the pre
      osteoblasts toward a mature state capable of mineralizing the extracellular
      matrix.

PMID- 25847600
TI  - Josef Rudinger Memorial Lecture: Use of peptides to modulate protein-protein
      interactions.
AB  - Peptides are destined to play a major role as therapeutic agents. My laboratory
      is contributing to speeding up this process. On the one hand, we devote efforts
      to studying the molecular details and dynamics of the events that occur during
      molecular recognition at protein surfaces. We succeeded to design and synthesize
      peptides able to modulate these recognition events either permanently or in
      response to light. On the other hand, we are discovering and designing peptides
      able to cross biological barriers. Our aim is to use these peptides as shuttles
      for targeting therapeutic agents to organs, tissues, or cells, with a special
      emphasis on drug delivery to the brain.

PMID- 25847601
TI  - Successful treatment of relapsed anaplastic large cell lymphoma with vinblastine
      monotherapy and allo-HSCT with reduced intensity conditioning regimen.
AB  - Relapsed anaplastic large cell lymphoma (ALCL) is chemosensitive, but recurrence
      is common. Although vinblastine (VLB) monotherapy is an effective treatment for
      relapsed ALCL, the optimal treatment duration is unknown, and some patients
      experience further relapse after completing the treatment. Allogeneic
      hematopoietic stem cell transplantation (allo-HSCT) is also an effective
      treatment for relapsed ALCL, although transplant-related toxicity is a problem.
      Here, we report an 11-year-old patient with relapsed ALCL who underwent induction
      therapy with VLB monotherapy and achieved complete remission (CR) after 12
      courses. CR was confirmed on positron emission tomography-computed tomography.
      The patient then underwent allo-HSCT with reduced intensity conditioning
      (fludarabine, melphalan, and low-dose total body irradiation). He developed grade
      II acute graft-versus-host disease (GVHD), which was successfully treated with
      methylprednisolone. There was no evidence of chronic GVHD. He has remained in CR
      without any complications for 19 months after allo-HSCT.

PMID- 25847602
TI  - Design, synthesis, antiviral activity and three-dimensional quantitative
      structure-activity relationship study of novel 1,4-pentadien-3-one derivatives
      containing the 1,3,4-oxadiazole moiety.
AB  - BACKGROUND: 1,4-Pentadien-3-one and 1,3,4-oxadiazole derivatives possess good
      antiviral activities, and their substructure units are usually used in antiviral
      agent design. In order to discover novel molecules with high antiviral
      activities, a series of 1,4-pentadien-3-one derivatives containing the 1,3,4
      oxadiazole moiety were designed and synthesised. RESULTS: Bioassays showed that
      most of the title compounds exhibited good inhibitory activities against tobacco
      mosaic virus (TMV) in vivo. The compound 8f possessing the best protective
      activity against TMV had an EC50 value of 135.56 mg L(-1) , which was superior to
      that of ribavirin (435.99 mg L(-1) ). Comparative molecular field analysis
      (CoMFA) and comparative molecular similarity index analysis (CoMSIA) techniques
      were used in three-dimensional quantitative structure-activity relationship (3D
      QSAR) studies of protective activities, with values of q(2) and r(2) for the
      CoMFA and CoMSIA models of 0.751 and 0.775 and 0.936 and 0.925 respectively.
      Compound 8k with higher protective activity (EC50 = 123.53 mg L(-1) ) according
      to bioassay was designed and synthesised on the basis of the 3D-QSAR models.
      CONCLUSION: Some of the title compounds displayed good antiviral activities. 3D
      QSAR models revealed that the appropriate compact electron-withdrawing and
      hydrophobic group at the benzene ring could enhance antiviral activity. These
      results could provide important structural insights for the design of highly
      active 1,4-pentadien-3-one derivatives.

PMID- 25847603
TI  - An amphetamine isomer whose efficacy and safety in humans has never been studied,
      beta-methylphenylethylamine (BMPEA), is found in multiple dietary supplements.
AB  - The amphetamine isomer beta-methylphenylethylamine (BMPEA) was first synthesized
      in the early 1930s, but its efficacy and safety in humans has not been studied.
      Recently, the United States Food and Drug Administration (FDA) detected BMPEA in
      dietary supplements labelled as containing Acacia rigidula. Over a year after the
      FDA reported its findings, we analyzed Acacia rigidula dietary supplements to
      determine if BMPEA had been removed. Supplements were analyzed using liquid
      chromatography-quadrupole time-of-flight mass spectrometry. Diluted methanolic
      extract from each supplement was run three times and each data set obtained was
      analyzed using Agilent MassHunter Qualitative Analysis. The presence of BMPEA was
      confirmed by accurate mass, retention time and mass spectra match against a
      reference standard. Quantification of BMPEA was determined using an eight-point
      calibration curve of spiked standard to a matrix blank. Twenty-one brands of
      Acacia rigidula supplements were analyzed. More than half (11/21; 52.4%) of the
      Acacia rigidula supplement brands contained BMPEA. The stimulant was present at
      quantities such that consumers following recommended maximum daily servings would
      consume a maximum of 93.7 mg of BMPEA per day. Consumers of Acacia rigidula
      supplements may be exposed to pharmacological dosages of an amphetamine isomer
      that lacks evidence of safety in humans. The FDA should immediately warn
      consumers about BMPEA and take aggressive enforcement action to eliminate BMPEA
      in dietary supplements. Copyright (c) 2015 John Wiley & Sons, Ltd. 

PMID- 25847604
TI  - Prostate-specific antigen-based prostate cancer screening: Past and future.
AB  - Prostate-specific antigen-based prostate cancer screening remains a controversial
      topic. Up to now, there is worldwide consensus on the statement that the harms of
      population-based screening, mainly as a result of overdiagnosis (the detection of
      clinically insignificant tumors that would have never caused any symptoms),
      outweigh the benefits. However, worldwide opportunistic screening takes place on
      a wide scale. The European Randomized Study of Screening for Prostate Cancer
      showed a reduction in prostate cancer mortality through prostate-specific antigen
      based-screening. These population-based data need to be individualized in order
      to avoid screening in those who cannot benefit and start screening in those who
      will. For now, lacking a more optimal screening approach, screening should only
      be started after the process of shared decision-making. The focus of future
      research is the reduction of unnecessary testing and overdiagnosis by further
      research to better biomarkers and the value of the multiparametric magnetic
      resonance imaging, potentially combined in already existing prostate-specific
      antigen-based multivariate risk prediction models. 

PMID- 25847605
TI  - Quantifying Unnecessary Normal Tissue Complication Risks due to Suboptimal
      Planning: A Secondary Study of RTOG 0126.
AB  - PURPOSE: The purpose of this study was to quantify the frequency and clinical
      severity of quality deficiencies in intensity modulated radiation therapy (IMRT)
      planning in the Radiation Therapy Oncology Group 0126 protocol. METHODS AND
      MATERIALS: A total of 219 IMRT patients from the high-dose arm (79.2 Gy) of RTOG
      0126 were analyzed. To quantify plan quality, we used established knowledge-based
      methods for patient-specific dose-volume histogram (DVH) prediction of organs at
      risk and a Lyman-Kutcher-Burman (LKB) model for grade >=2 rectal complications to
      convert DVHs into normal tissue complication probabilities (NTCPs). The LKB model
      was validated by fitting dose-response parameters relative to observed
      toxicities. The 90th percentile (22 of 219) of plans with the lowest excess risk
      (difference between clinical and model-predicted NTCP) were used to create a
      model for the presumed best practices in the protocol (pDVH0126,top10%). Applying
      the resultant model to the entire sample enabled comparisons between DVHs that
      patients could have received to DVHs they actually received. Excess risk
      quantified the clinical impact of suboptimal planning. Accuracy of pDVH
      predictions was validated by replanning 30 of 219 patients (13.7%), including
      equal numbers of presumed "high-quality," "low-quality," and randomly sampled
      plans. NTCP-predicted toxicities were compared to adverse events on protocol.
      RESULTS: Existing models showed that bladder-sparing variations were less
      prevalent than rectum quality variations and that increased rectal sparing was
      not correlated with target metrics (dose received by 98% and 2% of the PTV,
      respectively). Observed toxicities were consistent with current LKB parameters.
      Converting DVH and pDVH0126,top10% to rectal NTCPs, we observed 94 of 219
      patients (42.9%) with >=5% excess risk, 20 of 219 patients (9.1%) with >=10%
      excess risk, and 2 of 219 patients (0.9%) with >=15% excess risk. Replanning
      demonstrated the predicted NTCP reductions while maintaining the volume of the
      PTV receiving prescription dose. An equivalent sample of high-quality plans
      showed fewer toxicities than low-quality plans, 6 of 73 versus 10 of 73
      respectively, although these differences were not significant (P=.21) due to
      insufficient statistical power in this retrospective study. CONCLUSIONS: Plan
      quality deficiencies in RTOG 0126 exposed patients to substantial excess risk for
      rectal complications.

PMID- 25847606
TI  - Sparing healthy tissue and increasing tumor dose using bayesian modeling of
      geometric uncertainties for planning target volume personalization.
AB  - OBJECTIVE: To develop a mathematical tool that can update a patient's planning
      target volume (PTV) partway through a course of radiation therapy to more
      precisely target the tumor for the remainder of treatment and reduce dose to
      surrounding healthy tissue. METHODS AND MATERIALS: Daily on-board imaging was
      used to collect large datasets of displacements for patients undergoing external
      beam radiation therapy for solid tumors. Bayesian statistical modeling of these
      geometric uncertainties was used to optimally trade off between displacement data
      collected from previously treated patients and the progressively accumulating
      data from a patient currently partway through treatment, to optimally predict
      future displacements for that patient. These predictions were used to update the
      PTV position and margin width for the remainder of treatment, such that the
      clinical target volume (CTV) was more precisely targeted. RESULTS: Software
      simulation of dose to CTV and normal tissue for 2 real prostate displacement
      datasets consisting of 146 and 290 patients treated with a minimum of 30
      fractions each showed that re-evaluating the PTV position and margin width after
      8 treatment fractions reduced healthy tissue dose by 19% and 17%, respectively,
      while maintaining CTV dose. CONCLUSION: Incorporating patient-specific
      displacement patterns from early in a course of treatment allows PTV adaptation
      for the remainder of treatment. This substantially reduces the dose to healthy
      tissues and thus can reduce radiation therapy-induced toxicities, improving
      patient outcomes.

PMID- 25847607
TI  - Near Real-Time Assessment of Anatomic and Dosimetric Variations for Head and Neck
      Radiation Therapy via Graphics Processing Unit-based Dose Deformation Framework.
AB  - PURPOSE: The purpose of this study was to systematically monitor anatomic
      variations and their dosimetric consequences during intensity modulated radiation
      therapy (IMRT) for head and neck (H&N) cancer by using a graphics processing unit
      (GPU)-based deformable image registration (DIR) framework. METHODS AND MATERIALS:
      Eleven IMRT H&N patients undergoing IMRT with daily megavoltage computed
      tomography (CT) and weekly kilovoltage CT (kVCT) scans were included in this
      analysis. Pretreatment kVCTs were automatically registered with their
      corresponding planning CTs through a GPU-based DIR framework. The deformation of
      each contoured structure in the H&N region was computed to account for nonrigid
      change in the patient setup. The Jacobian determinant of the planning target
      volumes and the surrounding critical structures were used to quantify anatomical
      volume changes. The actual delivered dose was calculated accounting for the organ
      deformation. The dose distribution uncertainties due to registration errors were
      estimated using a landmark-based gamma evaluation. RESULTS: Dramatic
      interfractional anatomic changes were observed. During the treatment course of 6
      to 7 weeks, the parotid gland volumes changed up to 34.7%, and the center-of-mass
      displacement of the 2 parotid glands varied in the range of 0.9 to 8.8 mm. For
      the primary treatment volume, the cumulative minimum and mean and equivalent
      uniform doses assessed by the weekly kVCTs were lower than the planned doses by
      up to 14.9% (P=.14), 2% (P=.39), and 7.3% (P=.05), respectively. The cumulative
      mean doses were significantly higher than the planned dose for the left parotid
      (P=.03) and right parotid glands (P=.006). The computation including DIR and dose
      accumulation was ultrafast (~45 seconds) with registration accuracy at the
      subvoxel level. CONCLUSIONS: A systematic analysis of anatomic variations in the
      H&N region and their dosimetric consequences is critical in improving treatment
      efficacy. Nearly real-time assessment of anatomic and dosimetric variations is
      feasible using the GPU-based DIR framework. Clinical implementation of this
      technology may enable timely plan adaptation and improved outcome.

PMID- 25847608
TI  - Biomonitoring of metal exposure in children in a northern city of Japan.

PMID- 25847609
TI  - Caesarean Section has no impact on lung function at the age of 15 years.
AB  - BACKGROUND: Epidemiological studies and meta-analyses have shown an increased
      risk of childhood asthma for children born by Caesarean Section (C-Section).
      OBJECTIVE: To investigate the effect of delivery by C-Section on lung function
      and asthma in adolescence in a population-based prospective birth cohort of
      healthy full term newborns. METHODS: Questionnaire data on mode of delivery and
      asthma as well as spirometric measurements were available for 1850 adolescents at
      the age of 15 years, who participated in a follow-up examination of the GINIplus
      study. Linear regression models were used to examine associations between mode of
      delivery and lung function parameters. Two reference populations (Lunokid and
      GLI) were used to calculate the standardized z-scores of lung function
      parameters. RESULTS: The mean difference in lung function parameters for
      adolescents born by C-Section, compared to vaginal delivery was not statistically
      significant. The risk for developing asthma by the age of 15 years was not higher
      in children born by C-Section-OR: 0.87 (95% CI: 0.57, 1.33) adjusted for sex,
      age, study center, and parental education level. CONCLUSION: C-Section was not
      associated with impaired lung function or an increased risk of asthma at the age
      of 15 years in our birth cohort of healthy full term neonates.

PMID- 25847610
TI  - Trabeculectomy versus canaloplasty (TVC study) in the treatment of patients with
      open-angle glaucoma: a prospective randomized clinical trial.
AB  - PURPOSE: To compare the outcomes of canaloplasty and trabeculectomy in open-angle
      glaucoma. METHODS: This prospective, randomized clinical trial included 62
      patients who randomly received trabeculectomy (n = 32) or canaloplasty (n = 30)
      and were followed up prospectively for 2 years. Primary endpoint was complete
      (without medication) and qualified success (with or without medication) defined
      as an intraocular pressure (IOP) of <=18 mmHg (definition 1) or IOP <=21 mmHg and
      >=20% IOP reduction (definition 2), IOP >=5 mmHg, no vision loss and no further
      glaucoma surgery. Secondary endpoints were the absolute IOP reduction, visual
      acuity, medication, complications and second surgeries. RESULTS: Surgical
      treatment significantly reduced IOP in both groups (p < 0.001). Complete success
      was achieved in 74.2% and 39.1% (definition 1, p = 0.01), and 67.7% and 39.1%
      (definition 2, p = 0.04) after 2 years in the trabeculectomy and canaloplasty
      group, respectively. Mean absolute IOP reduction was 10.8 +/- 6.9 mmHg in the
      trabeculectomy and 9.3 +/- 5.7 mmHg in the canaloplasty group after 2 years (p =
      0.47). Mean IOP was 11.5 +/- 3.4 mmHg in the trabeculectomy and 14.4 +/- 4.2 mmHg
      in the canaloplasty group after 2 years. Following trabeculectomy, complications
      were more frequent including hypotony (37.5%), choroidal detachment (12.5%) and
      elevated IOP (25.0%). CONCLUSIONS: Trabeculectomy is associated with a stronger
      IOP reduction and less need for medication at the cost of a higher rate of
      complications. If target pressure is attainable by moderate IOP reduction,
      canaloplasty may be considered for its relative ease of postoperative care and
      lack of complications.

PMID- 25847611
TI  - A rapid, fully non-contact, hybrid system for generating Lamb wave dispersion
      curves.
AB  - A rapid, fully non-contact, hybrid system which encompasses an air-coupled
      transducer (ACT) and a laser Doppler vibrometer (LDV) is presented for profiling
      A0 Lamb wave dispersion of an isotropic aluminum plate. The ACT generates
      ultrasonic pressure incident upon the surface of the plate. The pressure waves
      are partially refracted into the plate. The LDV is employed to measure the out-of
      plane velocity of the excited Lamb wave mode at some distances where the Lamb
      waves are formed in the plate. The influence of the ACT angle of incidence on
      Lamb wave excitation is investigated and Snell's law is used to directly compute
      Lamb wave dispersion curves including phase and group velocity dispersion curves
      in aluminum plates from incident angles found to generate optimal A0 Lamb wave
      mode. The measured curves are compared to results obtained from a two-dimensional
      (2-D) Fast Fourier transform (FFT), Morlet wavelet transform (MWT) and
      theoretical predictions. It was concluded that the experimental results obtained
      using Snell's law concept are well in accordance with the theoretical solutions.
      The high degree of accuracy in the measured data with the theoretical results
      proved a high sensitivity of the air-coupled and laser ultrasound in
      characterizing Lamb wave dispersion in plate-like structures. The proposed non
      contact hybrid system can effectively characterize the dispersive relation
      without knowledge of neither the materials characteristics nor the mathematical
      model. 

PMID- 25847612
TI  - Tetramethylpyrazine reduces inflammation in liver fibrosis and inhibits
      inflammatory cytokine expression in hepatic stellate cells by modulating NLRP3
      inflammasome pathway.
AB  - Hepatic fibrosis is concomitant with liver inflammation, which has been
      highlighted as significant treatment of chronic liver disease. We previously
      demonstrated that tetramethylpyrazine (TMP), the effective component of
      Ligusticum chuanxiong Hort, can inhibit the activation of HSCs and consequential
      anti-hepatic fibrosis. In this study, our work demonstrated that TMP improved
      liver histological architecture, decreased hepatic enzyme levels and attenuated
      collagen deposition in the rat fibrotic liver. In addition, TMP significantly
      protected the liver from CCl4-caused injury and fibrogenesis by suppressing
      inflammation with reducing levels of inflammatory cytokines, including tumor
      necrosis factor-alpha (TNF-alpha), NLRP3, nuclear factor-kappa B (NF-kappaB) and
      interleukin-1beta (IL-1beta). Experiments in vitro showed that TMP inhibited
      inflammatory cytokine expression in HSCs associated with disrupting platelet
      derived growth factor-b receptor (PDGF-betaR)/NLRP3/caspase1 pathway. These data
      collectively indicate that TMP can attenuate liver inflammation in liver fibrosis
      and possibly by targeting HSCs via PDGF-betaR/NLRP3/caspase1 pathway. It provides
      novel mechanistic insights into TMP as a potential therapeutic remedy for hepatic
      fibrosis.

PMID- 25847613
TI  - Rocuronium and sugammadex under TOF monitoring on mECT.

PMID- 25847614
TI  - Ultrasound imaging of the musculocutaneous nerve of infants, preschool children,
      and school children.
AB  - The purpose of this imaging study was to investigate whether the musculocutaneous
      nerve could be visualized ultrasonographically in childhood and to assess how its
      visualization changes with age. Forty-two children participated in this
      prospective imaging study. The musculocutaneous nerve was sought both proximally
      (near the axillary artery) and distally (within the coracobrachialis muscle) by
      use of an linear ultrasound probe. Location of the musculocutaneous nerve was
      good (93 %) for all the children, both proximally and distally. For school-aged
      children, distal visualization of the musculocutaneous nerve reached 100 %. The
      musculocutaneous nerve is detectable in childhood by use of ultrasonography;
      success of detection was high for all the age groups examined.

PMID- 25847615
TI  - Clinical correlates of human leucocyte antigen (HLA)-G in systemic sclerosis.
AB  - Human leucocyte antigen (HLA)-G has a tolerogenic function and could play a role
      in the pathogenesis of immune-mediated diseases, including systemic sclerosis
      (SSc). The aim of this study was to evaluate HLA-G serum expression (sHLA-G) and
      the HLA-G gene 14 base pairs (bp) insertion/deletion (del(-)/del(+)) polymorphism
      in patients with Ssc, to search for possible associations with clinical and
      laboratory variables. sHLA-G was measured by enzyme-linked immunosorbent assay
      (ELISA) in sera from 77 patients with SSc and 32 healthy donors (HD); the 14 bp
      del(-)/del(+) polymorphism was evaluated by polymerase chain reaction (PCR)
      amplification of peripheral blood mononuclear cells (PBMC) genomic DNA. Receiver
      operating characteristics (ROC) analysis identified the HLA-G cut-off that best
      discriminated dichotomized clinical and serological variables, that was
      subsequently employed to subdivide SSc patients into HLA-G high (HLA-G(+)) and
      low (HLA-G(-)) profile groups. sHLA-G were not statistically different between
      SSc patients and HD, nor between distinct SSc autoantibody subsets. Subdividing
      SSc patients by HLA-G positivity or negativity yielded significant differences
      for the modified Rodnan skin score (mRss) (P = 0.032), 'general' (P = 0.031) and
      'kidney' (P = 0.028) Medsger severity scores (MSS) and disease activity index,
      and especially Delta heart/lung (P = 0.005). A worse 'general' MSS (P = 0.002)
      and Delta heart/lung (P = 0.011) were more frequent in the low sHLA-G group.
      These two variables and mRss were associated with sHLA-G levels at logistic
      regression analysis. Treatment had no influence on sHLA-G. Moreover, a higher
      frequency of scleredema was detected in the del(+)/del(+) than the del(-)/del(+)
      group (P = 0.04). These data suggest modulatory effects of sHLA-G on SSc.
      Prospective studies are needed to investigate a role in predicting the disease
      course.

PMID- 25847616
TI  - Mitochondrially-imported RNA in drug discovery.
AB  - The import of nuclear transcribed RNAs into mitochondria is an emerging area that
      presents a tremendous opportunity to develop human metabolic therapeutics.
      However, our knowledge base is quite limited. Much remains to be discovered
      regarding specific RNA localization and mechanisms of import. To identify novel
      RNAs imported into mitochondria, all RNAs within the mitochondria were
      characterized using next generation sequencing technology. Several nuclear
      transcribed RNAs were found within mitochondrial RNA (mtRNA) samples, including
      nuclear ribosomal RNAs, gamma satellite RNA and VL30 retroelement RNA. The
      presence of these RNAs within mitochondria coupled with RNA sequencing data from
      other laboratories investigating mtRNA processing, lead us to hypothesize that
      nuclease treatment of mitoplasts is insufficient for removing contaminating
      cytoplasmic RNAs. In contrast to traditional methodology, mitochondrial import
      was evaluated by qRT-PCR after stepwise removal of the outer mitochondrial
      membrane and subsequent lysis of mitochondria. This allowed identification of
      RNAs lost from the mitochondria with the same kinetics as mitochondrial DNA
      transcribed RNAs. This approach provided an improved evaluation of nuclear RNA
      enrichment within mitochondrial membranes to characterize nuclease protection and
      mitochondrial import and identify false-positive detection errors. qRT-PCR
      results confirmed the presence of VL30 retroelement RNA within mitochondria and
      question the hypothesis that the RNA component of RNase P is imported. These
      results illustrate a reliable approach for evaluating the presence of RNAs within
      mitochondria and open new avenues of investigation relating to mtRNA biology and
      in targeting mitochondrial based therapeutics.

PMID- 25847617
TI  - Preparation of desiccation-resistant aquatic-living Nostoc flagelliforme
      (Cyanophyceae) for potential ecological application.
AB  - Nostoc flagelliforme is a terrestrial edible cyanobacterium that grows in arid
      and semi-arid steppes. The continued over-exploitation in the last century has
      led to a sharp decline of this resource and a severe deterioration of the steppe
      ecology. Liquid-cultured N. flagelliforme serves as promising algal 'seeds' for
      resource restoration. In this study, macroscopic (or visible) aquatic-living
      colonies (MaACs) of N. flagelliforme were developed under weak light and high
      nitrogen conditions. In a 24 day shake-flask culture, MaACs were propagated by
      about 4.5-fold in biomass without loss of their macro-morphology; at the same
      time, the addition of weak UV-B treatment resulted in slightly bigger MaACs.
      Polyvinylpyrrolidone (PVP) k30, a water-soluble polymer, was used to generate the
      coating around MaACs, and after full desiccation, the coated MaACs could recover
      their photosynthetic physiological activity when rehydrated, with 4% PVP k30 for
      coating being most effective. In contrast, PVP k30-coated microscopic aquatic
      living colonies of N. flagelliforme and non-coated MaACs showed no resistance to
      full desiccation. The macroscopic morphology or structure of MaACs should be
      crucial for the formation of protection by PVP k30 coating. PVP k30-coated MaACs
      were more approaching to actual application for resource restoration. 

PMID- 25847618
TI  - Influence of morphine on medial prefrontal cortex alpha2 adrenergic system in
      passive avoidance learning in rats.
AB  - The prelimbic region of the medial prefrontal cortex (mPFC) is a brain area
      crucial for memory, attention, and decision making. It has been shown that alpha2
      adreneoceptors (alpha2-ARs) play a powerful role in regulating memory and
      attention functions in this region. Since many studies have demonstrated the
      impairment effect of morphine on memory through mPFC, we aimed to investigate the
      possible interaction between alpha2-ARs of the mPFC and morphine induced amnesia
      in passive avoidance learning in rats. Animals were bilaterally implanted with
      chronic cannulas in the mPFC, trained in the step-through type passive avoidance
      task, and tested 24h after training; step-through latencies were measured. Our
      data indicate that post-training i.p. administration of morphine (2.5, 5 and
      7.5mg/kg) dose-dependently reduced the step-through latency, showing an amnesic
      effect. Post-training intra-mPFC administration of yohimbine (an alpha2
      adrenergic antagonist, 0.125, 0.25 and 0.5MUg/rat) and clonidine (an alpha2
      adrenergic agonist, 0.001, 0.01 and 0.2MUg/rat), dose dependently impaired memory
      retrieval. Furthermore, post-training intra-mPFC microinjection of ineffective
      doses of yohimbine or clonidine significantly reversed the inhibitory effect of
      morphine on memory retrieval. Furthermore, SKF96365 (a presynaptic calcium
      channel blocker) reduced yohimbine and showed slight inhibition of clonidine
      effect. These results suggest that alpha2-ARs of the mPFC may play an important
      role in morphine-induced amnesia. 

PMID- 25847619
TI  - Antinociceptive, anti-inflammatory and smooth muscle relaxant activities of the
      pyrrolo[3,4-d]pyridazinone derivatives: Possible mechanisms of action.
AB  - The aim of this study was to evaluate the analgesic as well as anti-inflammatory
      activities of the new pyrrolo[3,4-d]pyridazinone derivatives. Moreover, the
      present study attempted to assess some of the mechanisms involved in the
      pharmacological activity of these compounds. In the previous studies it was shown
      that these compounds were highly active in the phenylbenzoquinone-induced
      'writhing syndrome' test and had much lower activity in the hot plate, which
      indicates that mainly peripheral mechanisms of analgesia are involved in their
      effects. In these extended studies the analgesic activity of two tested compounds
      (4c, 4f) was confirmed in some animal models of pain. The studied compounds
      showed a significant and dose-related antinociceptive effect in the models of
      pain induced by formalin, capsaicin and glutamic acid. Both compounds decreased
      the edema formation and one of them (4c) attenuated mechanical hyperalgesia in
      carrageenan-induced paw inflammation in rats. Furthermore, both compounds
      inhibited cell migration, plasma exudation and nociceptive reaction in zymosan A
      induced mouse peritonitis. In the subsequent studies, including experiments on
      isolated organs (ileum, trachea, aorta), radioligand assays and biochemical
      tests, it was demonstrated that analgesic and anti-inflammatory effects of the
      investigated structures are largely due to their competitive antagonism for
      histamine H1 receptor. The influence on the level of cAMP in inflammatory cells
      (shown in RAW 264.7 macrophages) and subsequent inhibition of cytokine (TNFalpha,
      IL-1beta) release can also be one of the important mechanisms of their action.
      Moreover some additional mechanisms may also be involved in the eventual
      analgesic effect of tested pyrrolo[3,4-d]pyridazinone derivatives. 

PMID- 25847620
TI  - Inhibiting cholesterol degradation induces neuronal sclerosis and epileptic
      activity in mouse hippocampus.
AB  - Elevations in neuronal cholesterol have been associated with several degenerative
      diseases. An enhanced excitability and synchronous firing in surviving neurons
      are among the sequels of neuronal death in these diseases and also in some
      epileptic syndromes. Here, we attempted to increase neuronal cholesterol levels,
      using a short hairpin RNA to suppress expression of the enzyme cytochrome P450
      family 46, subfamily A, polypeptide 1 gene (CYP46A1). This protein hydroxylates
      cholesterol and so facilitates transmembrane extrusion. A short hairpin RNA
      CYP46A1construction coupled to the adeno-associated virus type 5 was injected
      focally and unilaterally into mouse hippocampus. It was selectively expressed
      first in neurons of the cornu ammonis (hippocampus) (CA)3a region. Cytoplasmic
      and membrane cholesterol increased, and the neuronal soma volume increased and
      then decreased before pyramidal cells died. As CA3a pyramidal cells died,
      interictal electroencephalographic (EEG) events occurred during exploration and
      non-rapid eye movement sleep. With time, neuronal death spread to involve
      pyramidal cells and interneurons of the CA1 region. CA1 neuronal death was
      correlated with a delayed local expression of phosphorylated tau. Astrocytes were
      activated throughout the hippocampus and microglial activation was specific to
      regions of neuronal death. CA1 neuronal death was correlated with distinct
      aberrant EEG activity. During exploratory behaviour and rapid eye movement sleep,
      EEG oscillations at 7-10 Hz (theta) could accelerate to 14-21 Hz (beta) waves.
      They were accompanied by low-amplitude, high-frequency oscillations of peak power
      at ~300 Hz and a range of 250-350 Hz. Although episodes of EEG acceleration were
      not correlated with changes in exploratory behaviour, they were followed in some
      animals by structured seizure-like discharges. These data strengthen links
      between increased cholesterol, neuronal sclerosis and epileptic behaviour.

PMID- 25847621
TI  - Fast 4D flow MRI intracranial segmentation and quantification in tortuous
      arteries.
AB  - PURPOSE: To describe, validate, and implement a centerline processing scheme
      (CPS) for semiautomated segmentation and quantification in carotid siphons of
      healthy subjects. 4D flow MRI enables blood flow measurement in all major
      cerebral arteries with one scan. Clinical translational hurdles are time
      demanding postprocessing and user-dependence induced variability during analysis.
      MATERIALS AND METHODS: A CPS for 4D flow data was developed to automatically
      separate cerebral artery trees. Flow parameters were quantified at planes along
      the centerline oriented perpendicular to the vessel path. At 3T, validation
      against 2D phase-contrast (PC) magnetic resonance imaging (MRI) and 4D flow
      manual processing was performed on an intracranial flow phantom for constant
      flow, while pulsatile flow validation was performed in the internal carotid
      artery (ICA) of 10 healthy volunteers. The CPS and 4D manual processing times
      were measured and compared. Flow and area measurements were also demonstrated
      along the length of the ICA siphon. RESULTS: Phantom measurements for area and
      flow were highly correlated between the CPS and 2D measurements (area: R = 0.95,
      flow: R = 0.94), while in vivo waveforms were highly correlated (R = 0.93).
      Processing time was reduced by a factor of 4.6 compared with manual processing.
      Whole ICA measurements revealed a significantly decreased area in the most distal
      segment of the carotid siphon (P = 0.0017), with flow unchanged (P = 0.84).
      CONCLUSION: This study exhibits fast semiautomated analysis of intracranial 4D
      flow MRI. Internal consistency was shown through flow conservation along the
      tortuous ICA siphon, which is typically difficult to assess.

PMID- 25847622
TI  - The neurocognitive performance of female veterans with posttraumatic stress
      disorder.
AB  - Neurocognitive problems are common with posttraumatic stress disorder (PTSD) and
      are important to understand because of their association with the success of PTSD
      treatment and its potential neural correlates. To our knowledge, this is the
      first neurocognitive study in an all-female U.S. veteran sample, some of whom had
      PTSD. We examined neurocognitive performance and assessed whether learning
      deficits, common in PTSD, were associated with executive functioning. Veterans
      with PTSD (n = 56) and without (n = 53) were evaluated for psychiatric and
      neurocognitive status. The PTSD group had a lower estimated IQ (d = 0.53) and
      performed more poorly on all neurocognitive domains (d range = 0.57-0.88), except
      verbal retention (d = 0.04). A subset of the 2 groups that were matched on IQ and
      demographics similarly demonstrated poorer performance for the PTSD group on all
      neurocognitive domains (d range = 0.52-0.79), except verbal retention (d = 0.15).
      Within the PTSD group, executive functioning accounted for significant variance
      in verbal learning over and above IQ and processing speed (DeltaR(2) = .06), as
      well as depression (DeltaR(2) = .07) and PTSD severity (DeltaR(2) = .06). This
      study demonstrated that female veterans with PTSD performed more poorly than
      females without PTSD on several neurocognitive domains, including verbal
      learning, processing speed, and executive functioning. Replication of these
      results using a control group of veterans with more similar trauma exposure,
      history of mild traumatic brain injury, and psychiatric comorbidities would
      solidify these findings.

PMID- 25847623
TI  - Vasorelaxation induced by dodoneine is mediated by calcium channels blockade and
      carbonic anhydrase inhibition on vascular smooth muscle cells.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Dodoneine (Ddn) is one of the active compounds
      identified from Agelanthus dodoneifolius (DC.) Polhill and Wiens, a medicinal
      plant used in traditional medicine for the treatment of hypertension. This
      dihydropyranone exerts hypotensive and vasorelaxant effects on rats, and two
      molecular targets have been characterized: the carbonic anhydrase and the L-type
      calcium channel in cardiomyocytes with biochemical and electrophysiological
      techniques, respectively. To further evaluate the involvement of these two
      molecular targets in vasorelaxation, the effect of Ddn on rat vascular smooth
      muscle was investigated. MATERIAL AND METHODS: The effects of Ddn on L-type
      calcium current and on resting membrane potential were characterized in A7r5 cell
      line using the whole-cell patch-clamp configuration. The molecular identities of
      carbonic anhydrase isozymes in smooth muscle cells were examined with RT-PCR.
      Vascular response was measured on rat aortic rings in an organ bath apparatus and
      the effect of Ddn on intracellular pH was determined by flow cytometry using the
      pH-sensitive fluorescent probe BCECF-AM [2,7-Bis-(2-Carboxyethyl)-5-(and-6)
      Carboxyfluorescein, Acetoxymethyl Ester]. RESULTS: 100uM Ddn reduced calcium
      current density of about 30%. In addition, carbonic anhydrase II, III, XIII and
      XIV were shown to be expressed in rat aorta and inhibited in smooth muscle cells
      by Ddn. This inhibition resulted in a rise in pHi of about 0.31, leading to KCa
      channel activation, thereby inducing membrane hyperpolarization and
      vasorelaxation. The results of vascular reactivity experiments obtained with
      pharmacological tools acting on the L-type calcium current and carbonic anhydrase
      suggest that Ddn produces its vasorelaxant effect via the inhibition of these two
      molecular targets. CONCLUSION: This study demonstrates that Ddn induced
      vasorelaxation by targeting two proteins involved in the modulation of excitation
      contraction coupling: L-type calcium channels and carbonic anhydrase.

PMID- 25847624
TI  - Traditional medicine use by cancer patients in Thailand.
AB  - ETHNOBOTANICAL RELEVANCE: Cancer patients commonly use traditional medicines (TM)
      and in Thailand these are popular for both self-medication and as prescribed by
      TM practitioners, and are rarely monitored. A study was conducted at Wat
      Khampramong, a Thai Buddhist temple herbal medicine hospice, to document some of
      these practices as well as the hospice regime. MATERIALS AND METHODS: Cancer
      patients (n = 286) were surveyed shortly after admission as to which TMs they had
      previously taken and perceptions of effects experienced. They were also asked to
      describe their current symptoms. Treatment at the hospice is built upon an 11
      herb anti-cancer formula, yod-ya-mareng, prescribed for all patients, and
      ideally, its effects would have been evaluated. However other herbal medicines
      and holistic practices are integral to the regime, so instead we attempted to
      assess the value of the patients' stay at the hospice by measuring any change in
      symptom burden, as they perceived it. Surviving patients (n = 270) were therefore
      asked to describe their symptoms again just before leaving. RESULTS: 42% of
      patients (120/286; 95% CI 36.4%, 47.8%) had used herbal medicines before their
      arrival, with 31.7% (38/120; 95% CI 24%, 40.4%) using several at once. Mixed
      effects were reported for these products. After taking the herbal regime at
      Khampramong, 77% (208/270 95% CI; 71.7%, 81.7%) reported benefit, and a
      comparison of the incidence of the most common (pain, dyspepsia, abdominal or
      visceral pain, insomnia, fatigue) showed statistical significance (chi(2) 57.1,
      df 7, p < 0.001). CONCLUSIONS: A wide range of TMs is taken by cancer patients in
      Thailand and considered to provide more benefit than harm, and this perception
      extends to the temple regime. Patients reported a significant reduction in
      symptoms after staying at Khampramong, indicating an improvement in quality of
      life, the aim of hospices everywhere. Based on this evidence, it is not possible
      to justify the use of TM for cancer in general, but this study suggests that
      further research is warranted. The uncontrolled use of TMs, many of which are
      uncharacterised, raises concerns, and this work also highlights the fact that
      validated, robust methods of assessing holistic medical regimes are urgently
      needed.

PMID- 25847625
TI  - Health-related quality of life after radical prostatectomy depends on patient's
      age but not on comorbidities.
AB  - PURPOSE: Localized prostate cancer affects younger and healthy patients as well
      as older patients with comorbidities. The purpose of this study was to evaluate
      the effect of age and comorbidities on the quality-of-life (QoL) course before
      and after radical retropubic prostatectomy. PATIENTS AND METHODS: Overall, 374
      patients with localized prostate cancer scheduled for radical prostatectomy were
      prospectively included. The QoL questionnaire QLQ-C30 (European Organisation for
      Research and Treatment of Cancer) was completed 1 day before surgery and 3, 6, 9,
      and 12 months after radical prostatectomy. Sexual and urinary functions were not
      assessed in this analysis. Subgroups according to age at diagnosis (<=60,>60
      to<=70, and>70y) and comorbidities (Charlson scores<=2 and >=3) were defined.
      Subgroups were compared using the Wilcoxon-Mann-Whitney test, whereas changes in
      a group over time were analyzed with the Wilcoxon signed rank test. RESULTS: In
      all patient groups, no change was found 12 months after surgery compared with
      preoperative values in global health as well as functioning (role, physical,
      cognitive, and social). Emotional functioning improved significantly after
      surgery compared with preoperative functioning. Older patients (>70y) had better
      emotional and social functioning compared with younger patients (<=60y). The
      other scores were comparable between older and younger patients. Global health
      and physical, role, cognitive, and social functioning were independent of the
      number of comorbidities, although patients with a Charlson score>=3 did worse
      regarding fatigue and dyspnoe. CONCLUSION: The QoL of older patients or patients
      with multiple comorbidities is not negatively influenced by radical
      prostatectomy. This should be considered when discussing the indication for
      prostatectomy in older or comorbid patients.

PMID- 25847626
TI  - Novel homozygous mutation in KPTN gene causing a familial intellectual disability
      macrocephaly syndrome.
AB  - Recently, a novel autosomal recessive developmental delay-macrocephaly syndrome
      was described caused by homozygous or compound heterozygous mutations in the KPTN
      gene. All reported patients belonged to one large Amish kindred. We report on the
      second case of KPTN-related syndrome in two Estonian adult sibs. The brother and
      sister both have macrocephaly and moderate intellectual disability, and their
      verbal abilities are more affected than motor development. No notable minor
      anomalies are present. Behavioral problems and a few episodes of seizures were
      reported in the brother. Whole exome sequencing carried out from the brother's
      DNA sample identified homozygous one-nucleotide frameshift duplication c.665dupA
      (p.Q222fs) in the KPTN gene. Homozygosity of both affected sibs and
      heterozygosity of parents were confirmed by Sanger sequencing. Thus, we confirm
      the pathogenicity of KPTN mutations and further delineate the novel developmental
      delay-macrocephaly syndrome. We also support the hypothesis that KPTN-related
      syndrome is not restricted to the Amish population.

PMID- 25847627
TI  - Erratum to: Analysis of Programmed Death-1 in Patients with Psoriatic Arthritis.

PMID- 25847628
TI  - Selecting a prospective test for early detection of diabetic polyneuropathy.
AB  - Microneurolysis of entrapped peripheral nerve has the best chance of success when
      compression has not created significant axonal loss. The purpose of this study is
      to learn the best way to identify potential surgical candidates at the earliest
      time for intervention, by examining patients in a clinical setting using
      objective, electrodiagnostic nerve conduction studies (NCS), and subjective touch
      threshold studies, Semmes-Weinstein monofilaments (SWM) and Pressure-Specified
      Sensory DeviceTM (PSSD). Fifty-five patients with diabetic polyneuropathy over
      the age of 30 years were included. Neuropathy symptom score was the gold standard
      for statistical calculation, with a prevalence of 70%. In the symptomatic
      population, prevalence was 64% for NCS (n = 25), 59% for SWM (n = 43), and 88%
      for PSSD (n = 51). In the asymptomatic population, prevalence was 70% for NCS,
      27% for SWM, and 92% for PSSD. It is concluded that the PSSD is the most
      sensitive device of those tested for identifying peripheral neuropathy in an at
      risk population of patients.

PMID- 25847629
TI  - Novel olfactory ligands via terpene synthases.
AB  - A synthetic biology approach to the rational design of analogues of olfactory
      ligands by providing unnatural substrates for the enzyme synthesising (S)
      germacrene D, an olfactory ligand acting as a plant derived insect repellent, to
      produce novel ligands is described as a viable alternative to largely
      unsuccessful ligand docking studies. (S)-14,15-Dimethylgermacrene D shows an
      unexpected reversal in behavioural activity. 

PMID- 25847630
TI  - Efficacy of antimicrobial pullulan-based coating to improve internal quality and
      shelf-life of chicken eggs during storage.
AB  - There has been a growing interest in the use of natural materials as a delivery
      mechanism for antimicrobials and coatings in foods. The aim of the present study
      was to evaluate the effectiveness of pullulan coatings to improve internal
      quality and shelf-life of fresh eggs during 10 wk of storage at 25 and 4  degrees
      C. Three treatments of eggs were evaluated as follows; non-coated (control; C),
      coated with pullulan (P), and coated with pullulan containing nisin (N). The
      effects of the pullulan coatings on microbiological qualities, physical
      properties, and freshness parameters were investigated and compared with non
      coated eggs. For non-coated eggs, as storage time increased, yolk index, albumen
      index, and Haugh unit value decreased and weight loss increased. However,
      pullulan coatings (P or N) minimized weight loss (<1.5%) and preserved the
      albumen and yolk quality of eggs (with a final B grade) 3 wk longer than non
      coated eggs at 25  degrees C. At 4  degrees C, both P- and N-coated eggs went
      from AA to A grade after 9 wk and maintained the grade for 10 wk (4 wk longer
      than that of non-coated eggs). This study is the first to demonstrate that
      pullulan coatings can preserve the internal quality, prolong the shelf-life, and
      minimize weight loss of fresh eggs.

PMID- 25847631
TI  - Evaluation of tyrosine kinase receptors in brain metastases of clear cell renal
      cell carcinoma reveals cMet as a negative prognostic factor.
AB  - AIMS: Brain metastases (BMs) of clear cell renal cell carcinoma (ccRCC) are
      associated with a dismal prognosis, with limited treatment options. Tyrosine
      kinases are relevant 'druggable' biomarkers. The aim of this study was to
      evaluate the tyrosine kinase receptors anaplastic lymphoma kinase (ALK),
      epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor
      alpha (PDGFRA) and cMet in a large series of ccRCC BMs. METHODS AND RESULTS: ALK,
      EGFR, PDGFRA and cMet protein expression was determined by immunohistochemistry
      in 53 ccRCCs BMs and 12 matched primary tumours. ALK and MET gene status and copy
      number alterations of chromosome 7 were studied with fluorescence in-situ
      hybridization (FISH). Data on the expression of hypoxia-inducible factor 1alpha
      (HIF1alpha) and Ki67 and microvessel density were available from previous
      studies. ALK was negative in all analysed specimens. EGFR was overexpressed in 41
      of 51 (80.4%) BMs and in seven of eight primary tumours, PDGFRA was overexpressed
      in all BMs except one and in all primary tumours, and cMet was expressed in 26 of
      50 (52%) BMs and in two of seven primary tumours, and did not correlate with MET
      amplification or polysomy 7. cMet was the only parameter associated with
      significantly shorter BM-specific survival (median 8 months versus 33 months, P =
      0.005, Cox regression). CONCLUSIONS: EGFR, PDGFRA and cMet are commonly
      overexpressed in ccRCC BMs. cMet overexpression correlates with significantly
      shorter BM-specific survival.

PMID- 25847632
TI  - From emergent literacy to reading: how learning to read changes a child's brain.
AB  - The ability to comprehend language is uniquely human. Behavioural and
      neuroimaging data reinforce the importance of intact oral language as
      foundational for the establishment of proficient reading. However, proficient
      reading is achieved not only via intact biological systems, but also a
      stimulating Home Literacy Environment. CONCLUSION: Behavioural and neuroimaging
      correlates for linguistic ability and literacy exposure support the engagement of
      neural circuits related to reading acquisition.

PMID- 25847633
TI  - Behavioural and cognitive-behavioural interventions for outwardly-directed
      aggressive behaviour in people with intellectual disabilities.
AB  - BACKGROUND: Outwardly-directed aggressive behaviour is a significant part of
      problem behaviours presented by people with intellectual disabilities. Prevalence
      rates of up to 50% have been reported in the literature, depending on the
      population sampled. Such behaviours often run a long-term course and are a major
      cause of social exclusion. This is an update of a previously published systematic
      review (see Hassiotis 2004; Hassiotis 2008). OBJECTIVES: To evaluate the efficacy
      of behavioural and cognitive-behavioural interventions on outwardly-directed
      aggressive behaviour in people with intellectual disabilities when compared to
      standard intervention or wait-list controls. SEARCH METHODS: In April 2014 we
      searched CENTRAL, Ovid MEDLINE, Embase, and eight other databases. We also
      searched two trials registers, checked reference lists, and handsearched relevant
      journals to identify any additional trials. SELECTION CRITERIA: We included
      studies if more than four participants (children or adults) were allocated by
      random or quasi-random methods to either intervention, standard treatment, or
      wait-list control groups. DATA COLLECTION AND ANALYSIS: Two review authors
      independently identified studies and extracted and assessed the quality of the
      data. MAIN RESULTS: We deemed six studies (309 participants), based on adult
      populations with intellectual disabilities, suitable for inclusion in the current
      version of this review. These studies examined a range of cognitive-behavioural
      therapy (CBT) approaches: anger management (three studies (n = 235); one
      individual therapy and two group-based); relaxation (one study; n = 12),
      mindfulness based on meditation (one study; n = 34), problem solving and
      assertiveness training (one study; n = 28). We were unable to include any studies
      using behavioural interventions. There were no studies of children.Only one study
      reported moderate quality of evidence for outcomes of interest as assessed by the
      Grades of Recommendations, Assessment, Development and Evaluation (GRADE)
      approach. We judged the evidence for the remaining studies to be of very low to
      low quality. Most studies were at risk of bias in two or more domains: one study
      did not randomly allocate participants and in two studies the process of
      randomisation was unclear; in one study there was no allocation concealment and
      in three studies this was unclear; blinding of assessors did not occur in three
      studies; incomplete outcome data were presented in one study and unclear in two
      studies; there was selective reporting in one study; and other biases were
      present in one study and unclear in four studies.Three of the six studies showed
      some benefit of the intervention on improving anger ratings. We did not conduct a
      meta-analysis, as we considered the studies too heterogeneous to combine (e.g.
      due to differences in the types of participants, sample size interventions, and
      outcome measures).Follow-up data for anger ratings for both the treatment and
      control groups were available for two studies. Only one of these studies (n =
      161) had adequate long-term data (10 months), which found some benefit of
      treatment at follow-up (continued improvement in anger coping skills as rated by
      key workers; moderate-quality evidence).Two studies (n = 192) reported some
      evidence that the intervention reduces the number of incidents of aggression and
      one study (n = 28) reported evidence that the intervention improved mental health
      symptoms.One study investigated the effects of the intervention on quality of
      life and cost of health and social care utilisation. This study provided moderate
      quality evidence, which suggests that compared to no treatment, behavioural or
      cognitive-behavioural interventions do not improve quality of life at 16 weeks (n
      = 129) or at 10 months follow-up (n = 140), or reduce the cost of health service
      utilisation (n = 133).Only one study (n = 28) assessed adaptive functioning. It
      reported evidence that assertiveness and problem-solving training improved
      adaptive behaviour.No studies reported data on adverse events. AUTHORS'
      CONCLUSIONS: The existing evidence on the effectiveness of behavioural and
      cognitive-behavioural interventions on outwardly-directed aggression in children
      and adults with intellectual disabilities is limited. There is a paucity of
      methodologically sound clinical trials and a lack of long-term follow-up data.
      Given the impact of such behaviours on the individual and his or her support
      workers, effective interventions are essential. We recommend that randomised
      controlled trials of sufficient power are carried out using primary outcomes that
      include reduction in outward-directed aggressive behaviour, improvement in
      quality of life, and cost effectiveness.

PMID- 25847634
TI  - The cost and quality of cancer care.

PMID- 25847635
TI  - A new priority for low-income countries: fighting cancer.

PMID- 25847636
TI  - Quality-adjusted cost of care: a meaningful way to measure growth in innovation
      cost versus the value of health gains.
AB  - Technology drives both health care spending and health improvement. Yet policy
      makers rarely see measures of cost growth that account for both effects. To fill
      this gap, we present the quality-adjusted cost of care, which illustrates cost
      growth net of growth in the value of health improvements, measured as survival
      gains multiplied by the value of survival. We applied the quality-adjusted cost
      of care to two cases. For colorectal cancer, drug cost per patient increased by
      $34,493 between 1998 and 2005 as a result of new drug launches, but value from
      offsetting health improvements netted a modest $1,377 increase in quality
      adjusted cost of care. For multiple myeloma, new therapies increased treatment
      cost by $72,937 between 2004 and 2009, but offsetting health benefits lowered
      overall quality-adjusted cost of care by $67,863. However, patients with multiple
      myeloma on established first-line therapies saw costs rise without corresponding
      benefits. All three examples document rapid cost growth, but they provide starkly
      different answers to the question of whether society got what it paid for. 

PMID- 25847637
TI  - Cancer mortality reductions were greatest among countries where cancer care
      spending rose the most, 1995-2007.
AB  - Health care spending and health outcomes vary markedly across countries, but the
      association between spending and outcomes remains unclear. This inevitably raises
      questions as to whether continuing growth in spending is justified, especially
      relative to the rising cost of cancer care. We compared cancer care across
      sixteen countries over time, examining changes in cancer spending and two
      measures of cancer mortality (amenable and excess mortality). We found that
      compared to low-spending health systems, high-spending systems had consistently
      lower cancer mortality in the period 1995-2007. Similarly, we found that the
      countries that increased spending the most had a 17 percent decrease in amenable
      mortality, compared to 8 percent in the countries with the lowest growth in
      cancer spending. For excess mortality, the corresponding decreases were 13
      percent and 9 percent. Additionally, the rate of decrease for the countries with
      the highest spending growth was faster than the all-country trend. These findings
      are consistent with the existence of a link between higher cancer spending and
      lower cancer mortality. However, further work is needed to investigate the
      mechanisms that underlie this correlation.

PMID- 25847638
TI  - How state and federal policies as well as advances in genome science contribute
      to the high cost of cancer drugs.
AB  - During a time when cancer drug prices are increasing at an unprecedented rate, a
      debate has emerged as to whether these drugs continue to provide good value. In
      this article I argue that this debate is irrelevant because under today's highly
      distorted market, prices will not be set with value considerations in mind. As an
      alternative, I suggest considering the "value" of three policy changes-Medicare's
      "average sales price plus 6 percent" payment program, laws that require insurance
      coverage of all new cancer drugs, and the Affordable Care Act-that are fueling
      manufacturers' willingness to set higher prices. More important than these
      issues, however, is the revolution that is occurring in molecular biology and its
      impact on scientists' ability to detect changes in the cancer genome. The lowered
      cost of discovery is driving more competitors into the market, which under
      distorted pricing paradoxically encourages drug makers to charge ever higher
      prices for their products.

PMID- 25847639
TI  - National expenditure for false-positive mammograms and breast cancer
      overdiagnoses estimated at $4 billion a year.
AB  - Populationwide mammography screening has been associated with a substantial rise
      in false-positive mammography findings and breast cancer overdiagnosis. However,
      there is a lack of current data on the associated costs in the United States. We
      present costs due to false-positive mammograms and breast cancer overdiagnoses
      among women ages 40-59, based on expenditure data from a major US health care
      insurance plan for 702,154 women in the years 2011-13. The average expenditures
      for each false-positive mammogram, invasive breast cancer, and ductal carcinoma
      in situ in the twelve months following diagnosis were $852, $51,837 and $12,369,
      respectively. This translates to a national cost of $4 billion each year. The
      costs associated with false-positive mammograms and breast cancer overdiagnoses
      appear to be much higher than previously documented. Screening has the potential
      to save lives. However, the economic impact of false-positive mammography results
      and breast cancer overdiagnoses must be considered in the debate about the
      appropriate populations for screening.

PMID- 25847640
TI  - For uninsured cancer patients, outpatient charges can be costly, putting
      treatments out of reach.
AB  - Reimbursement information for public and private payers has long been available.
      However, information about charges-the amounts that providers request before
      payments are negotiated-has been scarce, particularly for outpatient care. Using
      the new Medicare Provider Utilization and Payment Data Public Use File and other
      sources, we evaluated physician charges, reimbursements by Medicare and large
      private health plans, and expected patient cost sharing for outpatient oncology
      care. In 2012 the average Medicare reimbursement for chemotherapy was 39.6
      percent of charges; for private insurance, the share was 55.7 percent. Uninsured
      patients faced potential prices for chemotherapy that were 2-43 times as much as
      the total Medicare-allowed amount and 2-5 times as much as the private insurance
      allowed amount. Charges for outpatient chemotherapy and office visits were
      substantially higher than insurer-reimbursed amounts, which is consistent with
      previous evidence about hospital charges. The charges for outpatient services
      underscore the pressure that the current system places on the people who are
      least able to pay. Encouraging rational pricing for health care services will be
      an important step toward ensuring access to care for everyone.

PMID- 25847641
TI  - Older women with localized breast cancer: costs and survival rates increased
      across two time periods.
AB  - Significant national attention has been paid to the rising costs of cancer care.
      However, few studies have evaluated the association between trends in costs and
      survival outcomes. We used the Surveillance, Epidemiology, and End Results (SEER)
      Program-Medicare linked database to compare changes in costs and survival rates
      over time, among women ages 67-94 who were diagnosed with stage II or III breast
      cancer in 1994-96 or 2004-06. We found that median cancer-related costs increased
      from $12,335 to $17,396 among women with stage II disease, and from $18,107 to
      $32,598 among women with stage III disease. Although the median cost of breast
      surgery declined between the two study periods, the median cost of chemo- and
      radiation therapy increased substantially, leading to an overall rise in cancer
      related costs. Meanwhile, adjusted overall five-year survival improved, from 67.8
      percent to 72.5 percent for women with stage II disease and from 38.5 percent to
      51.9 percent for those with stage III disease. These findings suggest that
      increases in cancer care costs have been accompanied by improved outcomes. Future
      work should identify opportunities to optimize efficiency in cancer care.

PMID- 25847642
TI  - Wide variation in payments for Medicare beneficiary oncology services suggests
      room for practice-level improvement.
AB  - In recent years many policy makers have recommended alternative payment models in
      medical oncology in order to reduce costs and improve patient outcomes. Yet
      information on how oncology practices differ in their use of key service
      categories is limited. We measured annual payments for key service categories
      delivered to fee-for-service Medicare beneficiaries receiving care from 1,534
      medical oncology practices in 2011-12. In 2012, differences in payments per
      beneficiary at the seventy-fifth-percentile practice compared to the twenty-fifth
      percentile practice were $3,866 for chemotherapy (including administration and
      supportive care drugs), $1,872 for acute medical hospitalizations, and $439 for
      advanced imaging. Supportive care drugs, bevacizumab, and positron-emission
      tomography accounted for the greatest percentage of variation. Average practice
      payments for service categories were highly correlated across years but not
      correlated with each other, which suggests that service categories may be
      affected by different physician practice characteristics. These differences, even
      when clinical guidelines exist, demonstrate the potential for quality improvement
      that could be accelerated through alternative payment models. 

PMID- 25847643
TI  - Early diffusion of gene expression profiling in breast cancer patients associated
      with areas of high income inequality.
AB  - With the Affordable Care Act reducing coverage disparities, social factors could
      prominently determine where and for whom innovations first diffuse in health care
      markets. Gene expression profiling is a potentially cost-effective innovation
      that guides chemotherapy decisions in early-stage breast cancer, but adoption has
      been uneven across the United States. Using a sample of commercially insured
      women, we evaluated whether income inequality in metropolitan areas was
      associated with receipt of gene expression profiling during its initial diffusion
      in 2006-07. In areas with high income inequality, gene expression profiling
      receipt was higher than elsewhere, but it was associated with a 10.6-percentage
      point gap between high- and low-income women. In areas with low rates of income
      inequality, gene expression profiling receipt was lower, with no significant
      differences by income. Even among insured women, income inequality may indirectly
      shape diffusion of gene expression profiling, with benefits accruing to the
      highest-income patients in the most unequal places. Policies reducing gene
      expression profiling disparities should address low-inequality areas and, in
      unequal places, practice settings serving low-income patients. 

PMID- 25847644
TI  - Uninsurance among young adults continues to decline, particularly in Medicaid
      expansion states.

PMID- 25847645
TI  - California emergency department visit rates for medical conditions increased
      while visit rates for injuries fell, 2005-11.
AB  - The emergency department (ED) is the source of most hospital admissions; provides
      care for patients with no other point of access to the health care system;
      receives advanced care referrals from primary care physicians; and provides
      surveillance data on injuries, infectious diseases, violence, and adverse drug
      events. Understanding the changes in the profile of disease in the ED can inform
      emergency services administration and planning and can provide insight into the
      public's health. We analyzed the trends in the diagnoses seen in California EDs
      from 2005 to 2011, finding that while the ED visit rate for injuries decreased by
      0.7 percent, the rate of ED visits for noninjury diagnoses rose 13.4 percent. We
      also found a rise in symptom-related diagnoses, such as abdominal pain, along
      with nervous system disorders, gastrointestinal disease, and mental illness.
      These trends point out the increasing importance of EDs in providing care for
      complex medical cases, as well as the changing nature of illness in the
      population needing immediate medical attention.

PMID- 25847646
TI  - Minimum-distance requirements could harm high-performing critical-access
      hospitals and rural communities.
AB  - Since the inception of the Medicare Rural Hospital Flexibility Program in 1997,
      over 1,300 rural hospitals have converted to critical-access hospitals, which
      entitles them to Medicare cost-based reimbursement instead of reimbursement based
      on the hospital prospective payment system (PPS). Several changes to eligibility
      for critical-access status have recently been proposed. Most of the changes focus
      on mandating that hospitals be located a certain minimum distance from the
      nearest hospital. Our study found that critical-access hospitals located within
      fifteen miles of another hospital generally are larger, provide better quality,
      and are financially stronger compared to critical-access hospitals located
      farther from another hospital. Returning to the PPS would have considerable
      negative impacts on critical-access hospitals that are located near another
      hospital. We conclude that establishing a minimum-distance requirement would
      generate modest cost savings for Medicare but would likely be disruptive to the
      communities that depend on these hospitals for their health care. 

PMID- 25847647
TI  - Reduced acute inpatient care was largest savings component of Geisinger Health
      System's patient-centered medical home.
AB  - Early evidence suggests that the patient-centered medical home has the potential
      to improve patient outcomes while reducing the cost of care. However, it is
      unclear how this care model achieves such desirable results, particularly its
      impact on cost. We estimated cost savings associated with Geisinger Health
      System's patient-centered medical home clinics by examining longitudinal clinic
      level claims data from elderly Medicare patients attending the clinics over a
      ninety-month period (2006 through the first half of 2013). We also used these
      data to deconstruct savings into its main components (inpatient, outpatient,
      professional, and prescription drugs). During this period, total costs associated
      with patient-centered medical home exposure declined by approximately 7.9
      percent; the largest source of this savings was acute inpatient care ($34, or 19
      percent savings per member per month), which accounts for about 64 percent of the
      total estimated savings. This finding is further supported by the fact that
      longer exposure was also associated with lower acute inpatient admission rates.
      The results of this study suggest that patient-centered medical homes can lead to
      sustainable, long-term improvements in patient health outcomes and the cost of
      care.

PMID- 25847648
TI  - Michigan's fee-for-value physician incentive program reduces spending and
      improves quality in primary care.
AB  - As policy makers and others seek to reduce health care cost growth while
      improving health care quality, one approach gaining momentum is fee-for-value
      reimbursement. This payment strategy maintains the traditional fee-for-service
      arrangement but includes quality and spending incentives. We examined Blue Cross
      Blue Shield of Michigan's Physician Group Incentive Program, which uses a fee-for
      value approach focused on primary care physicians. We analyzed the program's
      impact on quality and spending from 2008 to 2011 for over three million
      beneficiaries in over 11,000 physician practices. Participation in the incentive
      program was associated with approximately 1.1 percent lower total spending for
      adults (5.1 percent lower for children) and the same or improved performance on
      eleven of fourteen quality measures over time. Our findings contribute to the
      growing body of evidence about the potential effectiveness of models that align
      payment with cost and quality performance, and they demonstrate that it is
      possible to transform reimbursement within a fee-for-service framework to
      encourage and incentivize physicians to provide high-quality care, while also
      reducing costs.

PMID- 25847649
TI  - Care coordination program for Washington State Medicaid enrollees reduced
      inpatient hospital costs.
AB  - Managing clinically complex populations poses a major challenge for state
      agencies trying to control health care costs and improve quality of care for
      Medicaid beneficiaries. In Washington State a care coordination intervention, the
      Chronic Care Management program, was implemented for clinically complex Medicaid
      beneficiaries who met risk criteria defined by a predictive modeling algorithm.
      We used propensity score matching to evaluate the program's impact on health care
      spending and utilization and mortality. We found large and significant reductions
      in inpatient hospital costs ($318 per member per month) among patients who used
      the program. The estimated reduction in overall medical costs of $248 per member
      per month exceeded the cost of the intervention but did not reach statistical
      significance. These results suggest that well-designed targeted care coordination
      services could reduce health care spending for Medicaid beneficiaries with
      complex health care needs. 

PMID- 25847650
TI  - Making multipayer reform work: what can be learned from medical home initiatives.
AB  - Multipayer collaboratives of all types will encounter legal, logistical, and
      often political obstacles that multipayer medical home initiatives have already
      overcome. The seventeen multipayer medical home initiatives launched between 2008
      and 2014 all navigated four critical decision-making points: convening
      stakeholders; establishing provider participation criteria; determining payment;
      and measuring performance. Although we observed trends toward voluntary payer
      participation and more flexible participation criteria for both payers and
      providers, initiatives continue to vary widely, each shaped largely by its
      insurance market and policy environment. Medical home initiatives across the
      United States are demonstrating that multipayer reform, although complex and
      difficult to implement, is feasible when committed stakeholders negotiate
      strategies that are responsive to the local context. Their experiences can
      inform, and perhaps expedite, negotiations in current and future multipayer
      collaborations. 

PMID- 25847651
TI  - Large performance incentives had the greatest impact on providers whose quality
      metrics were lowest at baseline.
AB  - This study examined the impact of Fairview Health Services' primary care provider
      compensation model, in which 40 percent of compensation was based on clinic-level
      quality outcomes. Fairview Health Services is a Pioneer accountable care
      organization in Minnesota. Using publicly reported performance data from 2010 and
      2012, we found that Fairview's improvement in quality metrics was not greater
      than the improvement in other comparable Minnesota medical groups. An analysis of
      Fairview's administrative data found that the largest predictor of improvement
      over the first two years of the compensation model was primary care providers'
      baseline quality performance. Providers whose baseline performance was in the
      lowest tertile improved three times more, on average, across the three quality
      metrics studied than those in the middle tertile, and almost six times more than
      those in the top tertile. As a result, there was a narrowing of variation in
      performance across all primary care providers at Fairview and a narrowing of the
      gap in quality between providers who treated the highest-income patient panels
      and those who treated the lowest-income panels. The large quality incentive fell
      short of its overall quality improvement aim. However, the results suggest that
      payment reform may help narrow variation in primary care provider performance,
      which can translate into narrowing socioeconomic disparities.

PMID- 25847652
TI  - Efficacy and safety concerns are important reasons why the FDA requires multiple
      reviews before approval of new drugs.
AB  - The regulatory approval of new drugs by the Food and Drug Administration (FDA) is
      a long and complex process and often requires multiple cycles of review,
      potentially delaying patients' access to new and effective therapeutics. We used
      qualitative methods to characterize the safety and efficacy reasons why
      applications for novel therapeutics approved by the FDA between 2001 and 2011
      required multiple review cycles prior to approval. Among ninety-six applications
      approved between 2001 and 2011 that required multiple review cycles, safety
      concerns contributed to seventy-four (77.1 percent) and efficacy concerns to
      forty-three (44.8 percent). Our study suggests that multiple review cycles appear
      to play an important role in allowing the FDA to protect public health and in
      ensuring adequate understanding of clinical benefits and risks prior to approval.

PMID- 25847653
TI  - Insensible losses: when the medical community forgets the family.

PMID- 25847654
TI  - Foundation grants on access to primary care.

PMID- 25847656
TI  - Home-based medical care and the Triple Aim.

PMID- 25847657
TI  - Quality measures for home-based care.

PMID- 25847658
TI  - Home-based care: the authors reply.

PMID- 25847659
TI  - Errata.

PMID- 25847660
TI  - Bis(benzoyloxybenzyl)-DiPPro nucleoside diphosphates of anti-HIV active
      nucleoside analogues.
AB  - Nucleoside analogues are extensively used as antiviral and anticancer agents.
      Their efficiency is dependent on their metabolism into the ultimately active
      nucleoside triphosphates. Often one step or even more in the metabolism of the
      nucleoside to the triphosphate is inefficient. To overcome this hurdle, prodrugs
      of the nucleotides are needed. Bis(acyloxybenzyl)nucleoside diphosphates have
      been reported by us as a first example of an efficient nucleoside diphosphate
      prodrug (DiPPro nucleotides). Here, the synthesis and the properties of
      bis(benzoyloxybenzyl)nucleoside diphosphates of the nucleoside analogues d4T and
      AZT are disclosed. The synthesis was achieved by using a
      phosphoramidite/oxidation route. In chemical hydrolysis studies, most of the
      compounds formed a nucleoside diphosphate. This was confirmed in CEM cell
      extracts, although the prodrug stability in extracts was lower than in phosphate
      buffer. Furthermore, the stability and the amount of nucleoside diphosphate
      formed were dependent on the substituent in the benzoyl moiety. Some of the
      compounds were more active against HIV in thymidine kinase-deficient CEM/TK(-)
      cells than were d4T or AZT. 

PMID- 25847661
TI  - Erratum to: Visualization of osseointegration of maxilla and mandible dental
      implants.

PMID- 25847662
TI  - A knowledge-based algorithm for automatic detection of cephalometric landmarks on
      CBCT images.
AB  - PURPOSE: Cone-beam computed tomography (CBCT) is now an established component for
      3D evaluation and treatment planning of patients with severe malocclusion and
      craniofacial deformities. Precision landmark plotting on 3D images for
      cephalometric analysis requires considerable effort and time, notwithstanding the
      experience of landmark plotting, which raises a need to automate the process of
      3D landmark plotting. Therefore, knowledge-based algorithm for automatic
      detection of landmarks on 3D CBCT images has been developed and tested. METHODS:
      A knowledge-based algorithm was developed in the MATLAB programming environment
      to detect 20 cephalometric landmarks. For the automatic detection, landmarks that
      are physically adjacent to each other were clustered into groups and were
      extracted through a volume of interest (VOI). Relevant contours were detected in
      the VOI and landmarks were detected using corresponding mathematical entities.
      The standard data for validation were generated using manual marking carried out
      by three orthodontists on a dataset of 30 CBCT images as a reference. RESULTS:
      Inter-observer ICC for manual landmark identification was found to be excellent
      (>0.9) amongst three observers. Euclidean distances between the coordinates of
      manual identification and automatic detection through the proposed algorithm of
      each landmark were calculated. The overall mean error for the proposed method was
      2.01 mm with a standard deviation of 1.23 mm for all the 20 landmarks. The
      overall landmark detection accuracy was recorded at 64.67, 82.67 and 90.33 %
      within 2-, 3- and 4-mm error range of manual marking, respectively. CONCLUSIONS:
      The proposed knowledge-based algorithm for automatic detection of landmarks on 3D
      images was able to achieve relatively accurate results than the currently
      available algorithm.

PMID- 25847663
TI  - Stability, structure and scale: improvements in multi-modal vessel extraction for
      SEEG trajectory planning.
AB  - PURPOSE: Brain vessels are among the most critical landmarks that need to be
      assessed for mitigating surgical risks in stereo-electroencephalography (SEEG)
      implantation. Intracranial haemorrhage is the most common complication associated
      with implantation, carrying significantly associated morbidity. SEEG planning is
      done pre-operatively to identify avascular trajectories for the electrodes. In
      current practice, neurosurgeons have no assistance in the planning of electrode
      trajectories. There is great interest in developing computer-assisted planning
      systems that can optimise the safety profile of electrode trajectories,
      maximising the distance to critical structures. This paper presents a method that
      integrates the concepts of scale, neighbourhood structure and feature stability
      with the aim of improving robustness and accuracy of vessel extraction within a
      SEEG planning system. METHODS: The developed method accounts for scale and
      vicinity of a voxel by formulating the problem within a multi-scale tensor voting
      framework. Feature stability is achieved through a similarity measure that
      evaluates the multi-modal consistency in vesselness responses. The proposed
      measurement allows the combination of multiple images modalities into a single
      image that is used within the planning system to visualise critical vessels.
      RESULTS: Twelve paired data sets from two image modalities available within the
      planning system were used for evaluation. The mean Dice similarity coefficient
      was 0.89 +/- 0.04, representing a statistically significantly improvement when
      compared to a semi-automated single human rater, single-modality segmentation
      protocol used in clinical practice (0.80 +/- 0.03). CONCLUSIONS: Multi-modal
      vessel extraction is superior to semi-automated single-modality segmentation,
      indicating the possibility of safer SEEG planning, with reduced patient
      morbidity.

PMID- 25847664
TI  - Registration by interactive inverse simulation: application for adaptive
      radiotherapy.
AB  - PURPOSE: This paper introduces a new methodology for semi-automatic registration
      of anatomical structure deformations. The contribution is to use an interactive
      inverse simulation of physics-based deformable model, computed in real time.
      METHODS: The method relies on nonlinear finite element method (FEM) within a
      constraint-based framework. Given a set of few registered points provided by the
      user, a real-time optimization adapts the boundary conditions and(/or) some
      parameters of the FEM in order to obtain the adequate geometrical deformations.
      To dramatically fasten the process, the method relies on a projection of the
      model in the space of the optimization variables. In this reduced space, a
      quadratic programming problem is formulated and solved very quickly. The method
      is validated with numerical examples for retrieving some unknown parameters such
      as the Young's modulus and some pressures on the boundaries of the model.
      RESULTS: The approach is employed in the context of radiotherapy of the neck
      where weight loss during the 7 weeks of the therapy modifies the volume of the
      anatomical structures and induces large deformations. Indeed, sensitive
      structures such as the parotid glands may cross the target volume due to these
      deformations which leads to adverse effects for the patient. We thus apply the
      approach for the registration of the parotid glands during the radiotherapy of
      the head and neck cancer. CONCLUSIONS: The results show how the method could be
      used in a clinical routine and be employed in the planning in order to limit the
      radiations of these glands.

PMID- 25847665
TI  - Brain activation in parietal area during manipulation with a surgical robot
      simulator.
AB  - PURPOSE: we present an evaluation method to qualify the embodiment caused by the
      physical difference between master-slave surgical robots by measuring the
      activation of the intraparietal sulcus in the user's brain activity during
      surgical robot manipulation. We show the change of embodiment based on the change
      of the optical axis-to-target view angle in the surgical simulator to change the
      manipulator's appearance in the monitor in terms of hand-eye coordination. The
      objective is to explore the change of brain activation according to the change of
      the optical axis-to-target view angle. METHODS: In the experiments, we used a
      functional near-infrared spectroscopic topography (f-NIRS) brain imaging device
      to measure the brain activity of the seven subjects while they moved the hand
      controller to insert a curved needle into a target using the manipulator in a
      surgical simulator. The experiment was carried out several times with a variety
      of optical axis-to-target view angles. RESULTS: Some participants showed a
      significant peak (P value = 0.037, F-number = 2.841) when the optical axis-to
      target view angle was 75 degrees . CONCLUSIONS: The positional relationship
      between the manipulators and endoscope at 75 degrees  would be the closest to the
      human physical relationship between the hands and eyes.

PMID- 25847666
TI  - Open-source image registration for MRI-TRUS fusion-guided prostate interventions.
AB  - PURPOSE: We propose two software tools for non-rigid registration of MRI and
      transrectal ultrasound (TRUS) images of the prostate. Our ultimate goal is to
      develop an open-source solution to support MRI-TRUS fusion image guidance of
      prostate interventions, such as targeted biopsy for prostate cancer detection and
      focal therapy. It is widely hypothesized that image registration is an essential
      component in such systems. METHODS: The two non-rigid registration methods are:
      (1) a deformable registration of the prostate segmentation distance maps with B
      spline regularization and (2) a finite element-based deformable registration of
      the segmentation surfaces in the presence of partial data. We evaluate the
      methods retrospectively using clinical patient image data collected during
      standard clinical procedures. Computation time and Target Registration Error
      (TRE) calculated at the expert-identified anatomical landmarks were used as
      quantitative measures for the evaluation. RESULTS: The presented image
      registration tools were capable of completing deformable registration computation
      within 5 min. Average TRE was approximately 3 mm for both methods, which is
      comparable with the slice thickness in our MRI data. Both tools are available
      under nonrestrictive open-source license. CONCLUSIONS: We release open-source
      tools that may be used for registration during MRI-TRUS-guided prostate
      interventions. Our tools implement novel registration approaches and produce
      acceptable registration results. We believe these tools will lower the barriers
      in development and deployment of interventional research solutions and facilitate
      comparison with similar tools.

PMID- 25847667
TI  - Bone enhancement in ultrasound using local spectrum variations for guiding
      percutaneous scaphoid fracture fixation procedures.
AB  - PURPOSE: The scaphoid bone is the most frequently fractured bone in the wrist.
      When fracture fixation is indicated, a screw is inserted into the bone either in
      an open surgical procedure or percutaneously under fluoroscopic guidance. Due to
      the complex geometry of the wrist, fracture fixation is a challenging task.
      Fluoroscopic guidance exposes both the patient and the physician to ionizing
      radiation. Ultrasound-based guidance has been suggested as a real-time, radiation
      free alternative. The main challenge of using ultrasound is the difficulty in
      interpreting the images due to the low contrast and noisy nature of the data.
      METHODS: We propose a bone enhancement method that exploits local spectrum
      features of the ultrasound image. These features are utilized to design a set of
      quadrature band-pass filters and subsequently estimate the local phase symmetry,
      where high symmetry is expected at the bone locations. We incorporate the shadow
      information below the bone surfaces to further enhance the bone responses. The
      extracted bone surfaces are then used to register a statistical wrist model to
      ultrasound volumes, allowing the localization and interpretation of the scaphoid
      bone in the volumes. RESULTS: Feasibility experiments were performed using
      phantom and in vivo data. For phantoms, we obtain a surface distance error 1.08
      mm and an angular deviation from the main axis of the scaphoid bone smaller than
      5 degrees , which are better compared to previously presented approaches.
      CONCLUSION: The results are promising for further development of a surgical
      guidance system to enable accurate anatomy localization for guiding percutaneous
      scaphoid fracture fixations.

PMID- 25847668
TI  - Classification approach for automatic laparoscopic video database organization.
AB  - PURPOSE: One of the advantages of minimally invasive surgery (MIS) is that the
      underlying digitization provides invaluable information regarding the execution
      of procedures in various patient-specific conditions. However, such information
      can only be obtained conveniently if the laparoscopic video database comes with
      semantic annotations, which are typically provided manually by experts.
      Considering the growing popularity of MIS, manual annotation becomes a laborious
      and costly task. In this paper, we tackle the problem of laparoscopic video
      classification, which consists of automatically identifying the type of abdominal
      surgery performed in a video. In addition to performing classifications on the
      full recordings of the procedures, we also carry out sub-video and video clip
      classifications. These classifications are carried out to investigate how many
      frames from a video are needed to get a good classification performance and which
      parts of the procedures contain more discriminative features. METHOD: Our
      classification pipeline is as follows. First, we reject the irrelevant frames
      from the videos using the color properties of the video frames. Second, we
      extract visual features from the relevant frames. Third, we quantize the features
      using several feature encoding methods, i.e., vector quantization, sparse coding
      (SC), and Fisher encoding. Fourth, we carry out the classification using support
      vector machines. While the sub-video classification is carried out by uniformly
      downsampling the video frames, the video clip classification is carried out by
      taking three parts of the videos (i.e., beginning, middle, and end) and running
      the classification pipeline separately for every video part. Ultimately, we build
      our final classification model by combining the features using a multiple kernel
      learning (MKL) approach. RESULTS: To carry out the experiments, we use a dataset
      containing 208 videos of eight different surgeries performed by 10 different
      surgeons. The results show that SC with K-singular value decomposition (K-SVD)
      yields the best classification accuracy. The results also demonstrate that the
      classification accuracy only decreases by 3 % when solely 60 % of the video
      frames are utilized. Furthermore, it is also shown that the end part of the
      procedures is the most discriminative part of the surgery. Specifically, by using
      only the last 20 % of the video frames, a classification accuracy greater than 70
      % can be achieved. Finally, the combination of all features yields the best
      performance of 90.38 % accuracy. CONCLUSIONS: The SC with K-SVD provides the best
      representation of our videos, yielding the best accuracies for all features. In
      terms of information, the end part of the laparoscopic videos is the most
      discriminative compared to the other parts of the videos. In addition to their
      good performance individually, the features yield even better classification
      results when all of them are combined using the MKL approach.

PMID- 25847669
TI  - PCA-derived respiratory motion surrogates from X-ray angiograms for percutaneous
      coronary interventions.
AB  - PURPOSE: Intraoperative coronary motion modeling with motion surrogates enables
      prospective motion prediction in X-ray angiograms (XA) for percutaneous coronary
      interventions. The motion of coronary arteries is mainly affected by patients
      breathing and heartbeat. Purpose of our work is therefore to extract coronary
      motion surrogates that are related to respiratory and cardiac motion. In
      particular, we focus on respiratory motion surrogates extraction in this paper.
      METHODS: We propose a fast automatic method for extracting patient-specific
      respiratory motion surrogate from cardiac XA. The method starts with an image
      preprocessing step to remove all tubular and curvilinear structures from XA
      images, such as vessels and guiding catheters, followed by principal component
      analysis on pixel intensities. The respiratory motion surrogate of an XA image is
      then obtained by projecting its vessel-removed image onto the first principal
      component. RESULTS: This breathing motion surrogate was demonstrated to get high
      correlation with ground truth diaphragm motion (correlation coefficient over 0.9
      on average). In comparison with other related methods, the method we developed
      did not show significant difference (p > 0.05), but did improve robustness and
      run faster on monoplane and biplane data in retrospective and prospective
      scenarios. CONCLUSIONS: we developed and evaluated a method in extraction of
      respiratory motion surrogate from interventional X-ray images that is easy to
      implement and runs in real time and thus allows extracting respiratory motion
      surrogates during interventions.

PMID- 25847670
TI  - Data-driven spatio-temporal RGBD feature encoding for action recognition in
      operating rooms.
AB  - PURPOSE: Context-aware systems for the operating room (OR) provide the
      possibility to significantly improve surgical workflow through various
      applications such as efficient OR scheduling, context-sensitive user interfaces,
      and automatic transcription of medical procedures. Being an essential element of
      such a system, surgical action recognition is thus an important research area. In
      this paper, we tackle the problem of classifying surgical actions from video
      clips that capture the activities taking place in the OR. METHODS: We acquire
      recordings using a multi-view RGBD camera system mounted on the ceiling of a
      hybrid OR dedicated to X-ray-based procedures and annotate clips of the
      recordings with the corresponding actions. To recognize the surgical actions from
      the video clips, we use a classification pipeline based on the bag-of-words (BoW)
      approach. We propose a novel feature encoding method that extends the classical
      BoW approach. Instead of using the typical rigid grid layout to divide the space
      of the feature locations, we propose to learn the layout from the actual 4D
      spatio-temporal locations of the visual features. This results in a data-driven
      and non-rigid layout which retains more spatio-temporal information compared to
      the rigid counterpart. RESULTS: We classify multi-view video clips from a new
      dataset generated from 11-day recordings of real operations. This dataset is
      composed of 1734 video clips of 15 actions. These include generic actions (e.g.,
      moving patient to the OR bed) and actions specific to the vertebroplasty
      procedure (e.g., hammering). The experiments show that the proposed non-rigid
      feature encoding method performs better than the rigid encoding one. The
      classifier's accuracy is increased by over 4 %, from 81.08 to 85.53 %.
      CONCLUSION: The combination of both intensity and depth information from the RGBD
      data provides more discriminative power in carrying out the surgical action
      recognition task as compared to using either one of them alone. Furthermore, the
      proposed non-rigid spatio-temporal feature encoding scheme provides more
      discriminative histogram representations than the rigid counterpart. To the best
      of our knowledge, this is also the first work that presents action recognition
      results on multi-view RGBD data recorded in the OR.

PMID- 25847671
TI  - Toward knowledge-based liver surgery: holistic information processing for
      surgical decision support.
AB  - PURPOSE: Malignant neoplasms of the liver are among the most frequent cancers
      worldwide. Given the diversity of options for liver cancer therapy, the choice of
      treatment depends on various parameters including patient condition, tumor size
      and location, liver function, and previous interventions. To address this issue,
      we present the first approach to treatment strategy planning based on holistic
      processing of patient-individual data, practical knowledge (i.e., case
      knowledge), and factual knowledge (e.g., clinical guidelines and studies).
      METHODS: The contributions of this paper are as follows: (1) a formalized dynamic
      patient model that incorporates all the heterogeneous data acquired for a
      specific patient in the whole course of disease treatment; (2) a concept for
      formalizing factual knowledge; and (3) a technical infrastructure that enables
      storing, accessing, and processing of heterogeneous data to support clinical
      decision making. RESULTS: Our patient model, which currently covers 602 patient
      individual parameters, was successfully instantiated for 184 patients. It was
      sufficiently comprehensive to serve as the basis for the formalization of a total
      of 72 rules extracted from studies on patients with colorectal liver metastases
      or hepatocellular carcinoma. For a subset of 70 patients with these diagnoses,
      the system derived an average of [Formula: see text] assertions per patient.
      CONCLUSION: The proposed concept paves the way for holistic treatment strategy
      planning by enabling joint storing and processing of heterogeneous data from
      various information sources.

PMID- 25847672
TI  - Amphiphilic tobramycins with immunomodulatory properties.
AB  - Amphiphilic aminoglycosides (AAGs) are an emerging source of antibacterials to
      combat infections caused by antibiotic-resistant bacteria. Mode-of-action studies
      indicate that AAGs predominately target bacterial membranes, thereby leading to
      depolarization and increased permeability. To assess whether AAGs also induce
      host-directed immunomodulatory responses, we determined the AAG-dependent
      induction of cytokines in macrophages in the absence or presence of
      lipopolysaccharide (LPS). Our results show for the first time that AAGs can boost
      the innate immune response, specifically the recruitment of immune cells such as
      neutrophils required for the resolution of infections. Moreover, AAGs can
      selectively control inflammatory responses induced in the presence of endotoxins
      to prevent septic shock. In conclusion, our study demonstrates that AAGs possess
      multifunctional properties that combine direct antibacterial activity with host
      directed clearance effects reminiscent of those of host-defense peptides. 

PMID- 25847673
TI  - A comparative study of the effects of cholesterol and desmosterol on zwitterionic
      DPPC model membranes.
AB  - Desmosterol is a direct biosynthetic precursor of cholesterol in Bloch
      biochemical pathway of cholesterol biosynthesis and differs with cholesterol only
      by a double bond in carbon 24. In this study, we aimed to research for the first
      time comparative effects of cholesterol and its precursor desmosterol on
      dipalmitoyl phosphatidylcholine (DPPC) multilamellar vesicles (MLVs) by utilizing
      Fourier transform infrared (FTIR) spectroscopy and differential scanning
      calorimetry (DSC). Our DSC studies reveal that with the addition of increasing
      desmosterol and cholesterol concentrations into pure DPPC MLVs, the pretransition
      disappears, the main phase transition shifts to lower temperatures and then
      disappears. While the main phase transition is abolished at 25 mol% concentration
      of desmosterol, this disappearance of the main phase transition occurs at
      cholesterol concentration above 30 mol%. Our FTIR studies show that both
      desmosterol and cholesterol decrease the order in the gel phase, whereas they
      increase it in the liquid crystalline phase. Importantly, we found that the
      effect of desmosterol on membrane order is weaker than that of cholesterol in
      both phases. Moreover, desmosterol and cholesterol increase the dynamics of DPPC
      membranes in the gel phase, while they decrease it in the liquid crystalline
      phase. Both sterols also induce a decrease in the wavenumber values of the C=O
      stretching and PO2(-) antisymmetric double stretching bands of DPPC both in the
      gel and liquid crystalline phases, which points out hydrogen bonding in between
      the hydroxyl group of both sterols and the carbonyl and phosphate groups of DPPC
      membranes.

PMID- 25847675
TI  - Anti-inflammatory potential of saponins derived from cultured wild ginseng roots
      in lipopolysaccharide-stimulated RAW 264.7 macrophages.
AB  - Ginseng, namely the root of Panax ginseng Meyer, is a well-known traditional
      medicine that has been used in Asian countries for thousands of years. Ginseng
      saponins have been shown to exert a variety of prominent pharmacological effects
      in a number of diseases. The aim of the present study was to identify the anti
      inflammatory effects of total saponins extracted from cultured wild ginseng roots
      (TSWG) on lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. An elevated
      production of nitric oxide (NO) was detected in the RAW 264.7 cells in response
      to stimulation with LPS, as shown by NO detection assay using Griess reagent.
      However, pre-treatment with TSWG inhibited the production of NO through the
      suppression of inducible NO synthase gene expression. Furthermore, the LPS
      induced gene expression and production of tumor necrosis factor-alpha (TNF-alpha)
      and interleukin-1beta (IL-1beta) were significantly reduced by treatment with
      TSWG, as shown by ELISA, and western blot analysis and RT-PCR, respectively. In
      the LPS-stimulated RAW 264.7 cells, nuclear factor-kappaB (NF-kappaB) was
      translocated from the cytosol to the nucleus, while pre-treatment with TSWG
      induced the sequestration of NF-kappaB in the cytosol through the inhibition of
      the inhibitor of kappaB degradation, as shown by immunofluorescence staining.
      TSWG also contributed to the downregulation of mitogen-activated protein kinases
      and Akt in the LPS-stimulated RAW 264.7 cells. Additionally, in the TSWG-treated
      RAW 264.7 cells, we observed the activation of nuclear factor (erythroid-derived
      2)-like 2 and an increase in heme oxygenase-1 expression; these effects were
      associated with the inhibition of the generation of reactive oxygen species. The
      results from the present study indicate that TSWG exerts anti-inflammatory and
      antioxidant effects, suggesting that TSWG may be an effective therapeutic agent
      for inflammatory diseases and prevent cellular damage induced by oxidative
      stress.

PMID- 25847674
TI  - Microsporidia-host interactions.
AB  - Microsporidia comprise one of the largest groups of obligate intracellular
      pathogens and can infect virtually all animals, but host response to these fungal
      related microbes has been poorly understood. Several new studies of the host
      transcriptional response to microsporidia infection have found infection-induced
      regulation of genes involved in innate immunity, ubiquitylation, metabolism, and
      hormonal signaling. In addition, microsporidia have recently been shown to
      exploit host recycling endocytosis for exit from intestinal cells, and to
      interact with host degradation pathways. Microsporidia infection has also been
      shown to profoundly affect behavior in insect hosts. Altogether, these and other
      recent findings are providing much-needed insight into the underlying mechanisms
      of microsporidia interaction with host animals. 

PMID- 25847676
TI  - Development of a method to screen and isolate potential alpha-glucosidase
      inhibitors from Panax japonicus C.A. Meyer by ultrafiltration, liquid
      chromatography, and counter-current chromatography.
AB  - A new assay based on ultrafiltration, liquid chromatography and mass spectrometry
      was developed for the rapid screening and identification of the ligands for alpha
      glucosidase from the extract of Panax japonicus. Six saponins were identified as
      alpha-glucosidase inhibitors. Subsequently, the specific binding ligands, namely,
      notoginsenoside R1 , ginsenoside Rb1 , chikusetsusaponin V, chikusetsusaponin IV,
      chikusetsusaponin IVa, and ginsenoside Rd (the purities were 94.18, 95.43, 96.09,
      93.26, 94.50, 93.86%, respectively) were separated by counter-current
      chromatography using two-phase solvent systems composed of tert-butyl methyl
      ether, acetonitrile, 0.1% aqueous formic acid (3.8:1.0:4.4, v/v/v) and the
      solvent system composed of methylene chloride, isopropanol, methanol, 0.1%
      aqueous formic acid (5.8:1.0:6.0:2.2, v/v/v). The results demonstrate that
      ultrafiltration, liquid chromatography and mass spectrometry combined with high
      speed counter-current chromatography might provide not only a powerful tool for
      screening and isolating alpha-glucosidase inhibitors in complex samples but also
      a useful platform for discovering bioactive compounds for the prevention and
      treatment of diabetes mellitus. 

PMID- 25847677
TI  - Discrepant trends in income, drinking, and alcohol problems in an emergent
      economy: Brazil 2006 to 2012.
AB  - BACKGROUND: To examine the association between increases in income and self
      reported alcohol consumption, binge drinking, and alcohol problems in 2006 and
      2012 in Brazil. METHODS: Participants were interviewed as part of 2 multistage
      representative cluster samples of the Brazilian household population between
      November 2005 and April 2006 and between November 2011 and March 2012. The number
      of current drinkers during these 2 intervals (n = 1,379 and n = 1,907,
      respectively) comprised the sample analyzed. Four past-year outcome variables
      standard drinks per week, binge drinking, presence of alcohol-related
      social/health problems, and DSM-5 alcohol use disorder (AUD)-were estimated
      across income, age, and gender groups. Regression models were estimated to
      evaluate these and other sociodemographic effects on drinking and problem
      outcomes and to test for possible wave by income interactions. RESULTS: Response
      rates were 66.4% in 2006 and 77% in 2012. Income increases were seen in virtually
      all age-gender subgroups and were particularly pronounced for younger age groups
      and older women. Both genders reported increased drinks per week (men: 12.82,
      2006; 15.78, 2012; p < 0.01; women: 4.89, 2006; 7.66, 2012; p < 0.001) and
      proportion binge drinking (men: 57%, 2006; 66%, 2012; p < 0.05; women: 39%, 2006;
      48%, 2012; p < 0.05), although this was not seen in all gender and age groups.
      Social/health problem prevalence decreased among men (37%, 2006; 26%, 2012; p <
      0.001) and remained the same among women (13%, 2006; 14%, 2012). DSM-5 AUD
      decreased among men (34%, 2006; 24%, 2012; p < 0.01) and remained stable among
      women (14%, 2006; 16%, 2012). CONCLUSIONS: Brazilian economic development between
      2006 and 2012 led to a rise in income in several gender and age groups. Although
      not always directly associated with an observed increase in alcohol consumption,
      the rise in income may have created a sense of optimism that inhibited a rise in
      alcohol-related problems.

PMID- 25847679
TI  - Talairach methodology in the era of 3D multimodal imaging: "The song remains the
      same," but catchier, and therefore more helpful for clinical decision making and
      surgical planning in epilepsy surgery.

PMID- 25847678
TI  - The topical treatment of anthroponotic cutaneous leishmaniasis with the tincture
      of thioxolone plus benzoxonium chloride (Thio-Ben) along with cryotherapy: a
      single-blind randomized clinical trial.
AB  - A simple efficacious topical treatment for cutaneous leishmaniasis (CL) is still
      an unresolved challenge. This study aimed to evaluate the efficacy of the topical
      use of thioxolone plus benzoxonium chloride (Thio-Ben) tincture in combination
      with cryotherapy in comparison with intralesional meglumine antimoniate
      (Glucantime) along with cryotherapy in treating anthroponotic CL (ACL). The study
      was conducted in Leishmaniasis Center in Dadbin Health Care Clinic, Kerman, Iran.
      Sixty-four CL lesions were randomly assigned to receive Thio-Ben plus cryotherapy
      (TC) (n = 32) or Glucantime plus cryotherapy (GC) (n = 32). Thio-Ben was used
      topically every other day and Glucantime was used intralesionally once a week for
      a maximum of 3 months. In both study groups, cryotherapy was administered using
      liquid nitrogen once every 2 weeks. Of 64 recruited lesions, 47 lesions completed
      the study protocol. Twenty lesions (91%) in TC group and 23 lesions (92%) in GC
      group showed complete cure. TC group showed faster clinical response. Pain,
      hypersensitivity reaction, dizziness, and nausea were only seen in GC group. This
      study showed that the topical use of Thio-Ben combined with cryotherapy has a
      good efficacy in treating ACL with the benefit that Thio-Ben has more patient
      compliance and less side effects than intralesional Glucantime. 

PMID- 25847680
TI  - Heteroleptic bis(dipyrrinato)copper(II) and nickel(II) complexes.
AB  - Heteroleptic bis(dipyrrinato)copper(II) and nickel(II) complexes are synthesized.
      Their structures are determined by X-ray diffraction analysis, and their
      properties are investigated by using cyclic voltammetry, chronocoulometry, and
      UV/vis absorption spectroscopy.

PMID- 25847681
TI  - High juvenile hormone titre and abdominal activation of JH signalling may induce
      reproduction of termite neotenics.
AB  - Termite castes are a key example of polyphenism, in which reproductive division
      of labour is clearly seen in colonies. The reproductive castes in termites
      include primary and neotenic reproductives; primary reproductives found a new
      colony whereas neotenics succeed them in the reproductive role when the primary
      reproductives die or become senescent. Neotenics usually differentiate from
      nymphs or workers by developing functional gonads while retaining juvenile
      characteristics; however, the developmental mechanism during neotenic
      differentiation remains poorly understood. Juvenile hormone (JH) mediates a
      number of aspects of developmental regulation in caste differentiation in
      termites. In the present study we quantified JH titres in neotenic reproductives
      of Reticulitermes speratus, and compared these with other developmental stages.
      In addition, expression changes in JH signalling gene homologues (Methoprene
      tolerant [Met], Kruppel-homolog1, Broad-Complex) in the head, thorax and abdomen
      were investigated during neotenic differentiation. Finally, we examined the
      function of Met in reproduction of neotenics by RNA interference (RNAi). Our
      results showed that the JH titres of neotenics were significantly higher than
      those of nymphs and workers. JH signalling genes were highly expressed in
      neotenic abdomens, compared with those in workers and nymphs. Met RNAi resulted
      in the inhibition of vitellogenin gene expression in newly moulted neotenics.
      These results suggest that the fertility of neotenics might be controlled by a
      large increase of JH titres and body-part-specific activation of JH signalling
      pathways. 

PMID- 25847682
TI  - EuroSCORE is a predictor of postoperative pericardial effusion following heart
      transplantation.
AB  - BACKGROUND: Pericardial effusion is an early complication following orthotopic
      heart transplantation. Effusion that requires surgical intervention not only
      prolongs in-hospital stay but also increases early mortality rate. EuroSCORE is
      one of the most common methods for calculating predictive mortality in heart
      surgery. MATERIAL AND METHODS: We performed a retrospective analysis of 25
      patients (22 men and 3 women, mean age 49+/-12 years). Mortality risk by
      EuroSCORE was estimated prior to surgery. All patients were operated on with
      Lower-Shumway technique and treated with standard triple immunosuppressive
      regimen (tacrolimus, mycophenolate mofetil, and prednisolone). They were divided
      into 2 groups depending on postoperative pericardial effusion that required
      surgical intervention. There were 9 (36%) patients in the pericardial effusion
      group (PE group) and 16 (64%) in the control group (C group). RESULTS: There was
      1 death, on the 7th postoperative day, due to Clostridium difficile infection.
      Mean time of pericardial effusion echocardiographic detection was 9+/-2 days
      following surgery. The mean amount of fluid diagnosed in 4-chamber transthoracic
      echocardiography was 2.2+/-0.3 cm vs. 0.7+/-0.2 cm (p<0.05). Pericardial effusion
      followed thrombocytopenia of 98+/-17 vs. 172+/-26*109/L in PE and C group
      (p<0.05). Patients' mean intensive care unit time stay was 23+/-9 days and 11+/-7
      days in PE and C group, respectively (p<0.05). The overall hospitalization time
      was 38+/-12 days and 31+/-23 days in PE and C group, respectively (p<0.05). The
      discriminant analysis showed that EuroSCORE >16% is a single predicting variable
      for postoperative pericardial effusion (AUC 0.946, CI: 0.76-0.99). CONCLUSIONS:
      Pericardial effusion is a common (36%) complication following heart
      transplantation. It requires surgical intervention and prolongs intensive care
      unit stay and overall hospitalization. The discriminant analysis showed that the
      EuroSCORE >16% is a single predicting variable for postoperative pericardial
      effusion.

PMID- 25847684
TI  - Normothermic liver preservation: a new paradigm?
AB  - Despite increasing donor numbers, waiting lists and pre-transplant mortality
      continue to grow in many countries. The number of donor organs suitable for liver
      transplantation is restricted by cold preservation and ischemia-reperfusion
      injury (IRI). Transplantation of marginal donor organs has led to renewed
      interest in new techniques which have the potential to improve the quality of
      preservation, assess the quality of the organ and allow repair of the donor organ
      prior to transplantation. If successful, such techniques would not only improve
      the outcome of currently transplanted marginal livers, but also increase the
      donor pool. Experimental evidence suggests that preservation under near
      physiological conditions of temperature and oxygenation abrogates IRI.
      Normothermic perfusion maintains the organ in a physiological state, avoiding the
      depletion of cellular energy and the accumulation of waste products, which occurs
      with static cold storage. It enables viability assessment prior to
      transplantation thereby reducing the risk of transplanting inherently marginal
      organs. Here we review the use of normothermic machine perfusion as a means of
      organ preservation. 

PMID- 25847683
TI  - Lipoprotein receptor-related protein 6 is required for parathyroid hormone
      induced Sost suppression.
AB  - Parathyroid hormone (PTH) suppresses the expression of the bone formation
      inhibitor sclerostin (Sost) in osteocytes by inducing nuclear accumulation of
      histone deacetylases (HDACs) to inhibit the myocyte enhancer factor 2 (MEF2)
      dependent Sost bone enhancer. Previous studies revealed that lipoprotein receptor
      related protein 6 (LRP6) mediates the intracellular signaling activation and the
      anabolic bone effect of PTH. Here, we investigated whether LRP6 mediates the
      inhibitory effect of PTH on Sost using an osteoblast-specific Lrp6-knockout (LRP6
      KO) mouse model. An increased level of Sost mRNA expression was detected in femur
      tissue from LRP6-KO mice, compared to wild-type littermates. The number of
      osteocytes expressing sclerostin protein was also increased in bone tissue of
      LRP6-KO littermates, indicating a negative regulatory role of LRP6 on
      Sost/sclerostin. In wild-type littermates, intermittent PTH treatment
      significantly suppressed Sost mRNA expression in bone and the number of
      sclerostin(+) osteocytes, while the effect of PTH was much less significant in
      LRP6-KO mice. Additionally, PTH-induced downregulation of MEF2C and 2D, as well
      as HDAC changes in osteocytes, were abrogated in LRP6-KO mice. These data
      indicate that LRP6 is required for PTH suppression of Sost expression. 

PMID- 25847685
TI  - Microtensile bond strength of a resin-based fissure sealant to Er,Cr:YSGG laser
      etched primary enamel.
AB  - The aim of this study was to evaluate the effect of Er,Cr:YSGG laser pre
      treatment alone, or associated with acid-etching, on the microtensile bond
      strength of a resin-based fissure sealant to primary enamel. Twenty-five human
      primary molars were randomly divided into five groups including (1) 35 % acid
      etching, (2) 2.5-W laser etching, (3) 3.5-W laser etching, (4) 2.5-W laser
      etching + acid etching, and (5) 3.5-W laser etching + acid etching. Er,Cr:YSGG
      laser was used at a wavelength of 2.780 nm and pulse duration of 140-200 MUs with
      a repetition rate of 20 Hz. Following surface pre-treatment, the fissure sealant
      (ClinProTM, 3M Dental Products) was applied. Each tooth was sectioned and
      subjected to microtensile testing. Kruskal-Wallis test was used for statistical
      analysis. The level of significance was set at p < 0.05. The microtensile bond
      strength values of group 1 were significantly higher than those of group 2, while
      no statistically significant difference was detected between groups 1, 3, 4, and
      5. It was concluded that 3.5-W laser etching produced results comparable to
      conventional acid etching technique, whereas 2.5-W laser etching was not able to
      yield adequate bonding performance.

PMID- 25847688
TI  - Fine-tuning of single-molecule conductance by tweaking both electronic structure
      and conformation of side substituents.
AB  - Herein, we describe a method to fine-tune the conductivity of single-molecule
      wires by employing a combination of chemical composition and geometrical
      modifications of multiple phenyl side groups as conductance modulators embedded
      along the main axis of the electronic pathway. We have measured the single
      molecule conductivity of a novel series of phenyl-substituted carotenoid wires
      whose conductivity can be tuned with high precision over an order of magnitude
      range by modulating both the electron-donating character of the phenyl
      substituent and its dihedral angle. It is demonstrated that the electronic
      communication between the phenyl side groups and the molecular wire is maximized
      when the phenyl groups are twisted closer to the plane of the conjugated
      molecular wire. These findings can be refined to a general technique for
      precisely tuning the conductivity of molecular wires. 

PMID- 25847687
TI  - Enantioselective copper-catalyzed alkynylation of benzopyranyl oxocarbenium ions.
AB  - We have developed highly enantioselective, copper-catalyzed alkynylations of
      benzopyranyl acetals. By using a copper(I) catalyst equipped with a chiral
      bis(oxazoline) ligand, high yields and enantioselectivities are achieved in the
      alkynylation of widely available, racemic isochroman and chromene acetals to
      deliver alpha-chiral oxygen heterocycles. This method demonstrates that chiral
      organometallic nucleophiles can be successfully used in enantioselective
      additions to oxocarbenium ions. 

PMID- 25847686
TI  - The primate amygdala in social perception - insights from electrophysiological
      recordings and stimulation.
AB  - The role of the amygdala in emotion and social perception has been intensively
      investigated primarily through studies using functional magnetic resonance
      imaging (fMRI). Recently, this topic has been examined using single-unit
      recordings in both humans and monkeys, with a focus on face processing. The
      findings provide novel insights, including several surprises: amygdala neurons
      have very long response latencies, show highly nonlinear responses to whole
      faces, and can be exquisitely selective for very specific parts of faces such as
      the eyes. In humans, the responses of amygdala neurons correlate with internal
      states evoked by faces, rather than with their objective features. Current and
      future studies extend the investigations to psychiatric illnesses such as autism,
      in which atypical face processing is a hallmark of social dysfunction. 

PMID- 25847689
TI  - So You Want to Be in Journals, or What Happens When You Press "Send".

PMID- 25847690
TI  - Gastroretentive carbidopa/levodopa, DM-1992, for the treatment of advanced
      Parkinson's disease.
AB  - OBJECTIVES: This study was undertaken to compare efficacy, tolerability, and
      pharmacokinetics of DM-1992, an extended-release formulation of
      carbidopa/levodopa (CD/L-dopa) with immediate-release (IR) CD/L-dopa in patients
      with advanced Parkinson's disease. METHODS: This randomized, open-label,
      crossover study included a 3-d baseline and two 10-d treatment periods. Patients
      with daily OFF time of 2.5 h or more taking 400 mg or more L-dopa/d in four or
      more divided doses were titrated to stable regimens of DM-1992 2 times per day or
      CD/L-dopa IR 3 times to 8 times per day. Patients were allowed to take rescue
      CD/L-dopa as needed. Using home diaries, patients recorded OFF time and ON time
      with or without troublesome dyskinesia during baseline and treatment days 7
      through 9. During 12-h clinic visits on day 10, plasma samples were collected for
      pharmacokinetics, and motor performance was assessed hourly. RESULTS: Thirty-four
      patients were enrolled; mean baseline L-dopa dosage was 968 mg/d. After
      titration, CD/L-dopa IR was dosed 4.8 times per day and DM-1992, 2 times per day.
      Rescue CD/L-dopa IR was given 1.3 times during the DM-1992 arm and 0.2 times
      during the CD/L-dopa IR arm. The reduction from baseline in % OFF time was
      greater for DM-1992 compared with CD/L-dopa IR (-5.52% vs. +1.33%; P = 0.0471).
      At steady-state, compared with CD/L-dopa IR, DM-1992 exhibited a smoother plasma
      L-dopa concentration profile mostly because of a significantly higher (day 10)
      predose L-dopa concentration, associated with enhanced motor performance.
      Although more patients taking DM-1992 had one or more adverse events (AEs) than
      CD/L-dopa IR patients (35% vs. 15%), no pattern to the AEs was seen, nor any
      resulting discontinuations. CONCLUSIONS: DM-1992 was associated with a reduction
      in %OFF time compared with CD/L-dopa IR despite a reduced dosing frequency.
      Although the open-label study design and the greater number of rescue doses
      during the DM-1992 arm call for caution in interpreting the results, the elevated
      predose plasma L-dopa concentration (12 h after DM-1992 administration) lends
      objective support to our findings, suggesting that phase 3 studies are warranted.

PMID- 25847691
TI  - Fluorescence fingerprint as an instrumental assessment of the sensory quality of
      tomato juices.
AB  - BACKGROUND: Sensory analysis is an important standard for evaluating food
      products. However, as trained panelists and time are required for the process,
      the potential of using fluorescence fingerprint as a rapid instrumental method to
      approximate sensory characteristics was explored in this study. RESULTS: Thirty
      five out of 44 descriptive sensory attributes were found to show a significant
      difference between samples (analysis of variance test). Principal component
      analysis revealed that principal component 1 could capture 73.84 and 75.28%
      variance for aroma category and combined flavor and taste category respectively.
      Fluorescence fingerprints of tomato juices consisted of two visible peaks at
      excitation/emission wavelengths of 290/350 and 315/425 nm and a long narrow
      emission peak at 680 nm. The 680 nm peak was only clearly observed in juices
      obtained from tomatoes cultivated to be eaten raw. The ability to predict overall
      sensory profiles was investigated by using principal component 1 as a regression
      target. Fluorescence fingerprint could predict principal component 1 of both
      aroma and combined flavor and taste with a coefficient of determination above
      0.8. CONCLUSION: The results obtained in this study indicate the potential of
      using fluorescence fingerprint as an instrumental method for assessing sensory
      characteristics of tomato juices.

PMID- 25847692
TI  - Integration analysis of miRNA and mRNA expression profiles in swine testis cells
      infected with Japanese encephalitis virus.
AB  - To elucidate the role of microRNAs (miRNA) in the regulation of gene expression
      in Japanese encephalitis virus (JEV) infected swine testis (ST) cells, we
      analyzed miRNA and mRNA expression profiles of JEV infected ST cells by high
      throughput sequencing technology as compared to uninfected controls. The results
      showed that 104 known miRNAs and 9 new miRNA candidates were differentially
      expressed in ST cells after JEV infection. We identified 396 differentially
      expressed mRNAs. Bioinformatics analysis identified 435 known miRNA-mRNA
      interaction pairs and 94 novel miRNA-mRNA interaction pairs involving miRNAs
      inversely correlated with the expression of their predicted target mRNAs. The
      known miRNAs inversely correlated with their target genes were involved in the
      biological processes of immunity, cytokine production, inflammation, and
      apoptosis. Selected miRNA-mRNA interactions were validated by luciferase reporter
      assay. Overall, our findings indicate that miRNAs may play critical roles in the
      pathogenesis of JEV infection.

PMID- 25847693
TI  - Inflammasome signaling pathways exert antiviral effect against Chikungunya virus
      in human dermal fibroblasts.
AB  - Arboviruses represent an emerging threat to human. They are transmitted to
      vertebrates by the bite of infected arthropods. Early transmission to vertebrates
      is initiated by skin puncture and deposition of virus in this organ. However,
      events at the bite site remain largely unknown. Here, we report that Chikungunya
      virus (CHIKV) and West Nile virus (WNV), despite belonging to distinct viral
      families, elicit a common antiviral signature in primary human dermal
      fibroblasts, attesting for the up regulation of interferon signaling pathways and
      leading to an increased expression of IFN-beta, interleukins and chemokines.
      Remarkably, CHIKV and WNV enhance IL-1beta expression and induce maturation of
      caspase-1, indicating the capacity of these pathogens to elicit activation of the
      inflammasome program in resident skin cells. CHIKV and WNV also induce the
      expression of the inflammasome sensor AIM2 in dermal fibroblasts, whereas
      inhibition of caspase-1 and AIM2 with siRNA interferes with both CHIKV- and WNV
      induced IL-1beta production by these cells. Finally, inhibition of the
      inflammasome via caspase-1 silencing was found to enhance CHIKV replication in
      dermal fibroblasts. Together, these results indicate that the skin contributes to
      the pro-inflammatory and anti-viral microenvironment via the activation of the
      inflammasome in the early stages following infection with arboviruses.

PMID- 25847694
TI  - Molecular characterization and genetic susceptibility of sapovirus in children
      with diarrhea in Burkina Faso.
AB  - Sapoviruses (SaVs) are a common cause of gastroenteritis in children. In sub
      Saharan Africa, there is a scarcity of information regarding SaV as an
      etiological agent of diarrhea. Here, we investigated the prevalence, molecular
      characterization and clinico-epidemiological features of SaV infections in
      children less than 5years of age with diarrhea in Burkina Faso. We further
      investigated the role of type 1 histo blood group antigens as susceptibility
      factors. In total, 309 fecal and 208 saliva samples from diarrheal children in
      Ouagadougou, Burkina Faso, were collected between May 2009 and March 2010. SaV
      was detected using real-time PCR, and genogrouped/genotyped by PCR or sequencing.
      Saliva samples were ABO, Lewis and secretor phenotyped using in house ELISA
      assays. We found a high prevalence (18%) and large genetic diversity with all 4
      human genogroups, and 9 genotypes/genoclusters circulating during the study
      period. The SaV infections were generally associated with milder symptoms, and
      neither ABH, Lewis or secretor phenotypes affected susceptibility to SaV
      infections.

PMID- 25847695
TI  - Emergence of multireassortant bluetongue virus serotype 4 in Hungary.
AB  - The genome sequence and the phylogenetic relationships of a serotype 4 bluetongue
      virus (BTV-4) emerged during 2014 in Hungary are described in this study. Genome
      segment 2 encoding the major neutralization antigen, VP2, shared moderate
      sequence similarity (nt, ? 94.3%) with the corresponding gene of contemporary and
      historic homotypic bluetongue viruses, whereas genome segments S1, S4, S5, S7-S10
      were typically more closely related to the cognate genes of heterotypic isolates.
      Importantly, in many gene phylogenies the Hungarian BTV-4 strain showed genetic
      relationship to BTV strains identified in outbreaks in the western Mediterranean
      basin. Our results indicate the identified Hungarian bluetongue virus strain
      evolved through reassortment involving multiple genome segments from various
      heterotypic bluetongue viruses.

PMID- 25847696
TI  - Intrasegmental recombination does not contribute to the long-term evolution of
      group A rotavirus.
AB  - Rotavirus is a genetically diverse pathogen with an eleven-segmented, double
      stranded RNA genome. Intrasegmental recombination has been proposed as a
      potential mechanism to generate antigenic diversity and a possible route of
      escape from vaccine-imposed selective pressure. Here intrasegmental recombination
      was studied by performing a genome-wide scan across the eleven genome segments of
      797 publically available rotavirus strains. Sixty-two sequences, or 0.7% of
      sequences analyzed, have evidence of intrasegmental homologous recombination.
      None of the specific recombination events is seen in more than one sequence. This
      uniqueness is consistent with either a spurious finding of recombination or the
      possibility that recombinant sequences arise naturally but are rapidly purged
      from the rotavirus population through selection. Arguments for the former
      explanation are presented. This analysis finds no evidence that intrasegmental
      recombination leads to ongoing transmission or plays a constructive role in
      rotavirus evolution. These results have practical implications for phylogenetic
      analyses and suggest a fundamental constraint that may have shaped rotavirus
      genome structure and evolution.

PMID- 25847697
TI  - Genomic characterization of EmsB microsatellite loci in Echinococcus
      multilocularis.
AB  - EmsB is a molecular marker applied to Echinococcus multilocularis genotyping
      studies. This marker has largely been used to investigate the epidemiology of the
      parasite in different endemic foci. The present study has lifted the veil on the
      genetic structure of this microsatellite. By in silico analysis on the E.
      multilocularis genome the microsatellite was described in about 40 copies on the
      chromosome 5 of the parasite. Similar structure was found in the relative
      parasite Echinococcus granulosus, where the microsatellite was firstly described.
      The present study completes the first investigations made on the EmsB
      microsatellite origins and confirms the reliability of this highly discriminant
      molecular marker.

PMID- 25847698
TI  - Genotypic diversity of multidrug-, quinolone- and extensively drug-resistant
      Mycobacterium tuberculosis isolates in Thailand.
AB  - Drug-resistant tuberculosis (TB), which includes multidrug-resistant (MDR-TB),
      quinolone-resistant (QR-TB) and extensively drug-resistant tuberculosis (XDR-TB),
      is a serious threat to TB control. We aimed to characterize the genotypic
      diversity of drug-resistant TB clinical isolates collected in Thailand to
      establish whether the emergence of drug-resistant TB is attributable to
      transmitted resistance or acquired resistance. We constructed the first molecular
      phylogeny of MDR-TB (n=95), QR-TB (n=69) and XDR-TB (n=28) in Thailand based on
      spoligotyping and proposed 24-locus multilocus variable-number of tandem repeat
      analysis (MLVA). Clustering analysis was performed using the unweighted pair
      group method with arithmetic mean. Spoligotyping identified the Beijing strain
      (SIT1) as the most predominant genotype (n=139; 72.4%). The discriminatory power
      of 0.9235 Hunter-Gaston Discriminatory Index (HGDI) with the 15-locus variable
      number tandem repeats of mycobacterial interspersed repetitive units typing was
      improved to a 0.9574 HGDI with proposed 24-locus MLVA, thereby resulting in the
      subdivision of a large cluster of Beijing strains (SIT1) into 17 subclusters. We
      identified the spread of drug-resistant TB clones caused by three different MLVA
      types in the Beijing strain (SIT1) and a specific clone of XDR-TB caused by a
      rare genotype, the Manu-ancestor strain (SIT523). Overall, 49.5% of all isolates
      were clustered. These findings suggest that a remarkable transmission of drug
      resistant TB occurred in Thailand. The remaining 50% of drug-resistant TB
      isolates were unique genotypes, which may have arisen from the individual
      acquisition of drug resistance. Our results suggest that transmitted and acquired
      resistance have played an equal role in the emergence of drug-resistant TB.
      Further characterization of whole genome sequences of clonal strains could help
      to elucidate the mycobacterial genetic factors relevant for drug resistance,
      transmissibility and virulence.

PMID- 25847699
TI  - Comparative effectiveness of surgery and radiosurgery for stage I non-small cell
      lung cancer.
AB  - BACKGROUND: Although surgery is the standard treatment for early-stage non-small
      cell lung cancer (NSCLC), stereotactic body radiotherapy (SBRT) has been
      disseminated as an alternative therapy. The comparative mortalities and
      toxicities of these treatments for patients of different life expectancies are
      unknown. METHODS: The Surveillance, Epidemiology, and End Results-Medicare linked
      database was used to identify patients who were 67 years old or older and
      underwent SBRT or surgery for stage I NSCLC from 2007 to 2009. Matched patients
      were stratified into short life expectancies (<5 years) and long life
      expectancies (>=5 years). Mortality and complication rates were compared with
      Poisson regression. RESULTS: Overall, 367 SBRT patients and 711 surgery patients
      were matched. Acute toxicity (0-1 month) was lower from SBRT versus surgery (7.9%
      vs 54.9%, P < .001). At 24 months after treatment, there was no difference (69.7%
      vs 73.9%, P = .31). The incidence rate ratio (IRR) for toxicity from SBRT versus
      surgery was 0.74 (95% confidence interval [CI], 0.64-0.87). Overall mortality was
      lower with SBRT versus surgery at 3 months (2.2% vs 6.1%, P = .005), but by 24
      months, overall mortality was higher with SBRT (40.1% vs 22.3%, P < .001). For
      patients with short life expectancies, there was no difference in lung cancer
      mortality (IRR, 1.01; 95% CI, 0.40-2.56). However, for patients with long life
      expectancies, there was greater overall mortality (IRR, 1.49; 95% CI, 1.11-2.01)
      as well as a trend toward greater lung cancer mortality (IRR, 1.63; 95% CI, 0.95
      2.79) with SBRT versus surgery. CONCLUSIONS: SBRT was associated with lower
      immediate mortality and toxicity in comparison with surgery. However, for
      patients with long life expectancies, there appears to be a relative benefit from
      surgery versus SBRT.

PMID- 25847700
TI  - Genomewide analysis of phytochrome proteins in the phylum Basidiomycota.
AB  - Phytochromes are photoreceptor proteins involved in the detection of the red and
      far-red regions of the visible light spectrum. Fungal phytochromes are hybrid
      histidine kinases with a conserved domain architecture composed of an N-terminal
      photosensory module and a C-terminal regulatory output module that includes the
      histidine kinase and response regulator receiver domains. In this study, we have
      analyzed the distribution, domain architecture, and phylogenetic analysis of
      phytochrome proteins in 47 published genome sequences among the phylum
      Basidiomycota. Genome analysis revealed that almost every genome of
      basidiomycetes contained at least one gene encoding a phytochrome protein. Domain
      architecture of fungal phytochromes was completely conserved in the identified
      phytochromes of basidiomycetes, and phylogenetic analysis clustered these
      proteins into clades related with the phylogenetic classification of this fungal
      phylum. 

PMID- 25847701
TI  - One-Pot Preparation of Inert Well-Defined Polymers by RAFT Polymerization and In
      Situ End Group Transformation.
AB  - A one-pot procedure that straightforwardly combines reversible addition
      fragmentation chain transfer (RAFT) polymerization and end group transformation
      to remove the RAFT end groups is developed for the synthesis of well-defined
      poly(meth)acrylates and polyacrylamides with inert end groups. This procedure
      only requires the addition of an amine at the end of the standard RAFT
      polymerization procedure, which avoids the separation and purification of the
      intermediate polymers and, hence, extremely reduces the working time and utilized
      amount of solvents. Upon addition of the amine, a thiol group is formed by
      aminolysis of the thiocarbonylthio group, which subsequently undergoes Michael
      addition with unreacted monomer leading to an inert thioether functionalized
      polymer. 

PMID- 25847703
TI  - Using bonding to guide transition state optimization.
AB  - Optimization of a transition state typically requires both a good initial guess
      of the molecular structure and one or more computationally demanding Hessian
      calculations to converge reliably. Often, the transition state being optimized
      corresponds to the barrier in a chemical reaction where bonds are being broken
      and formed. Utilizing the geometries and bonding information for reactants and
      products, an algorithm is outlined to reliably interpolate an initial guess for
      the transition state geometry. Additionally, the change in bonding is also used
      to increase the reliability of transition state optimizations that utilize
      approximate and updated Hessian information. These methods are described and
      compared against standard transition state optimization methods.

PMID- 25847702
TI  - Validation and cross-cultural adaptation of the 'Fibromyalgia Participation
      Questionnaire' to the Spanish population: study protocol.
AB  - There are few high-quality instruments to evaluate the participation and social
      functioning of fibromyalgia patients. The Fibromyalgia Participation
      Questionnaire (FPQ) is a questionnaire that evaluates these aspects with high
      reliability and validity in its German original version. The aim of this work was
      to describe the translation and cross-cultural adaptation process of the FPQ into
      Spanish and its validation to ensure the equivalence against the original
      version. The questionnaire will be translated according to the FACIT methodology,
      and it will be tested in the Clinical Management Unit of North Almeria Health
      Area. This methodology includes several stages: double forward translation,
      reconciled version, back-translation, review of the previous versions and
      development of the prefinal version for the pretest. Once the pretest ends, the
      final version of the questionnaire will be developed, which will be subjected to
      a validation process to study its psychometric properties. Reliability will be
      studied by internal consistency and test-retest reliability through Cronbach's
      alpha and Pearson's correlation coefficient, respectively. External and construct
      validity will be analysed using correlation coefficients, content validity with
      an empirical analysis, and a differential item functioning analysis will be
      employed to measure discriminative validity. The presence of ceiling and floor
      effects will be calculated too. The validation of the FPQ into different
      languages will allow better evaluation and treatment based on the observed
      limitations fibromyalgia patients suffer from, as well as bringing the
      possibility to compare between other countries and generalize its use in the
      scientific community. 

PMID- 25847704
TI  - High diagnostic accuracy of the Sysmex XT-2000iV delta total nucleated cells on
      effusions for feline infectious peritonitis.
AB  - BACKGROUND: The DeltaWBC (the ratio between DIFF and BASO counts of the Sysmex XT
      2000iV), hereafter defined as DeltaTNC (total nucleated cells), is high in
      effusions due to feline infectious peritonitis (FIP), as cells are entrapped in
      fibrin clots formed in the BASO reagent. Similar clots form in the Rivalta's
      test, a method with high diagnostic accuracy for FIP. OBJECTIVES: The objective
      of this study was to determine the diagnostic accuracy for FIP and the optimal
      cutoff of DeltaTNC. METHODS: After a retrospective search of our database, DIFF
      and BASO counts, and the DeltaTNC from cats with and without FIP were compared to
      each other. Sensitivity, specificity, and positive and negative likelihood ratios
      (LR+, LR-) were calculated. A ROC curve was designed to determine the cutoff for
      best sensitivity and specificity. RESULTS: Effusions from 20 FIP and 31 non-FIP
      cats were analyzed. The DeltaTNC was higher (P < .001), and BASO and DIFF counts
      were lower (P < .001 and P < .05) in FIP than in non-FIP cats. Only 2 FIP cats
      with atypical effusions had a DeltaTNC < 3.0. The cutoff identified by the ROC
      curve (area under curve: 0.94; P < .001) was 1.7 (Sensitivity = 90.0%;
      Specificity = 93.53%; LR+ = 13.9; LR- = 0.1). A DeltaTNC > 2.5 had 100%
      specificity. CONCLUSIONS: The DeltaTNC has a high diagnostic accuracy for FIP
      related effusions by providing an estimate of precipitable proteins, as the
      Rivalta's test, in addition to the cell count. As fibrin clots result in false
      lower BASO counts, the DeltaTNC is preferable to the WBC count generated by the
      BASO channel alone in suspected FIP effusions.

PMID- 25847706
TI  - Genetic admixture supports an ancient hybrid origin of the endangered Hawaiian
      duck.
AB  - Speciation is regarded primarily as a bifurcation from an ancestral species into
      two distinct taxonomic units, but gene flow can create complex signals of
      phylogenetic relationships, especially among different loci. We evaluated several
      hypotheses that could account for phylogenetic discord between mitochondrial DNA
      (mtDNA) and nuclear DNA (nuDNA) within Hawaiian duck (Anas wyvilliana), including
      stochastic lineage sorting, mtDNA capture and widespread genomic introgression.
      Our results best support the hypothesis that the contemporary Hawaiian duck is
      descended from an ancient hybridization event between the mallard (Anas
      platyrhynchos) and Laysan duck (Anas laysanensis). Whereas mtDNA clearly shows a
      sister relationship between Hawaiian duck and mallard, nuDNA is consistent with a
      genetic mosaic with nearly equal contributions from Laysan duck and mallard. In
      addition, coalescent analyses suggest that gene flow from either mallard or
      Laysan duck, depending on the predefined tree topology, is necessary to explain
      contemporary genetic diversity in Hawaiian ducks, and these estimates are more
      consistent with ancient, rather than contemporary, hybridization. Time since
      divergence estimates suggest that the genetic admixture event occurred around the
      Pleistocene-Holocene boundary, which is further supported by circumstantial
      evidence from the Hawaiian subfossil record. Although the extent of reproductive
      isolation from either putative parental taxon is not currently known, these
      species are phenotypically, genetically and ecologically different, and they meet
      primary criteria used in avian taxonomy for species designation. Thus, the
      available data are consistent with an admixed origin and support the hypothesis
      that the Hawaiian duck may represent a young hybrid species.

PMID- 25847705
TI  - The ACVRL1 c.314-35A>G polymorphism is associated with organ vascular
      malformations in hereditary hemorrhagic telangiectasia patients with ENG
      mutations, but not in patients with ACVRL1 mutations.
AB  - Hereditary hemorrhagic telangiectasia (HHT) is characterized by vascular
      malformations (VMs) and caused by mutations in TGFbeta/BMP9 pathway genes, most
      commonly ENG or ACVRL1. Patients with HHT have diverse manifestations related to
      skin and mucosal telangiectases and organ VMs, including arteriovenous
      malformations (AVM). The clinical heterogeneity of HHT suggests a role for
      genetic modifiers. We hypothesized that the ACVRL1 c.314-35A>G and ENG c.207G>A
      polymorphisms, previously associated with sporadic brain AVM, are associated with
      organ VM in HHT. We genotyped these variants in 716 patients with HHT and
      evaluated association of genotype with presence of any organ VM, and specifically
      with brain VM, liver VM and pulmonary AVM, by multivariate logistic regression
      analyses stratified by HHT mutation. Among all patients with HHT, neither
      polymorphism was significantly associated with presence of any organ VM; ACVRL1
      c.314-35A>G showed a trend toward association with pulmonary AVM (OR = 1.48, P =
      0.062). ACVRL1 c.314-35A>G was significantly associated with any VM among
      patients with HHT with ENG (OR = 2.66, P = 0.022), but not ACVRL1 (OR = 0.79, P =
      0.52) mutations. ACVRL1 c.314-35A>G was also associated with pulmonary AVM and
      liver VM among ENG mutation heterozygotes. There were no significant associations
      between ENG c.207G>A and any VM phenotype. These results suggest that common
      polymorphisms in HHT genes other than the mutated gene modulate phenotype
      severity of HHT disease, specifically presence of organ VM.

PMID- 25847707
TI  - Prevalence of Baseline Erectile Dysfunction (ED) in an Australian Cohort of Men
      with Localized Prostate Cancer.
AB  - INTRODUCTION: Erectile dysfunction (ED) is a common complication following
      prostate cancer treatment. Post-treatment erectile function (EF) preservation is
      strongly dependent on the baseline EF prior to treatment. AIM: To assess the
      baseline EF among patients with localized prostate cancer, and the factors
      associated with baseline EF. METHODS: All men with clinically localized prostate
      cancer had their baseline EF assessed prior to brachytherapy at our institution.
      Six hundred ninety-nine men who completed the International Index of Erectile
      Function five-item questionnaires pre-treatment between 2001 and 2013 were
      included in the study. Data on patient factors (medical comorbidities and smoking
      history) and prostate cancer clinicopathological characteristics were recorded.
      Ordinal logistic regressions were used to estimate the effects of each variable
      on the severity of ED. MAIN OUTCOME MEASURES: Baseline EF among men with
      localized prostate cancer, and factors associated with ED. RESULTS: Prior to
      permanent seed brachytherapy, 335 (48%) patients reported no ED, 129 (17%) mild
      ED, 42 (6%) mild-moderate ED, 37 (5%) moderate ED, and 165 (24%) severe ED. In
      multivariate analyses, age, diabetes, and hypertension remained to be
      independently associated with ED, with diabetes most strongly associated with
      worse ED (odds ratio = 2.6; 95% confidence interval = 1.3-5.3). CONCLUSIONS: ED
      is common among patients with localized prostate cancer prior to any curative
      treatment. Assessment of baseline ED is important prior to curative treatment of
      prostate cancer in order to offer appropriate advise on likelihood of EF
      preservation post-treatment and avoid patient dissatisfaction with treatment
      outcomes due to unrealistic expectations.

PMID- 25847715
TI  - Intraocular BDNF promotes ectopic branching, alters motility and stimulates
      abnormal collaterals in regenerating optic fibers.
AB  - A great deal of effort has been invested in using trophic factors and other
      bioactive molecules to promote cell survival and axonal regeneration in the adult
      central nervous system. Far less attention has been paid to investigating
      potential effects that trophic factors may have that might interfere with
      recovery. In the visual system, BDNF has been previously reported to prevent
      regeneration. To test if BDNF is inherently incompatible with regeneration, BDNF
      was given intraocularly during optic nerve regeneration in the adult goldfish. In
      vivo imaging and anatomical analysis of selectively labeled axons were used as a
      sensitive assay for effects on regeneration within the tectum. BDNF had no
      detectable inhibitory effect on the ability of axons to regenerate. Normal
      numbers of axons regenerated into the tectum, exhibited dynamic growth and
      retractions similar to controls, and were able to navigate to their correct
      target zone in the tectum. However, BDNF was found to have additional effects
      that adversely affected the quality of regeneration. It promoted premature
      branching at ectopic locations, diminished the growth rate of axons through the
      tectum, and resulted in the formation of ectopic collaterals. Thus, although BDNF
      has robust effects on axonal behavior, it is, nevertheless, compatible with
      axonal regeneration, axon navigation and the formation of terminal arbors. 

PMID- 25847716
TI  - Differential regulation of HIF-3alpha in LPS-induced BV-2 microglial cells:
      Comparison and characterization with HIF-1alpha.
AB  - Hypoxia inducible factor(s) (HIF) are transcription factors that respond to a low
      level of oxygen or hypoxic conditions. The HIF pathway has been poorly studied
      under neuroinflammatory conditions, and no reports are available on the
      regulation of HIF-3alpha. Several studies have established that non-hypoxic
      stimuli can modulate the HIF pathway in a cell-specific manner. Recent reports
      suggest that hypoxia elicits inflammation or that inflammation during hypoxia is
      involved in a wide array of human diseases. In the present study, we used
      lipopolysaccharide (LPS), a well know inflammatory agent, to characterize the HIF
      3alpha expression pattern and compare it with that of HIF-1alpha under
      inflammatory conditions in BV-2 microglial cells. Moreover, we used reactive
      oxygen species inhibitors (rotenone, diphenyleneiodonium, and N-acetyl-L
      cysteine) under inflammatory conditions to determine the role of the functional
      electron transport chain in the regulation of HIF-3alpha in BV-2 microglial
      cells. Additionally, we utilized YC-1, a specific inhibitor of HIF-1alpha, to
      determine the role of HIF-3alpha in inflammatory conditions after inhibiting the
      HIF-1alpha pathway. YC-1 inhibited nuclear localization of HIF-1alpha following
      treatment with LPS in BV-2 microglia cells. Immunoblot and immunocytochemistry
      revealed a transient effect on HIF-3alpha after pre-treating the cells with YC-1.
      Furthermore, we determined the role of nuclear factor kappa B (NF-kappaB) in the
      regulation of HIF-3alpha using the NF-kappaB inhibitor PDTC in LPS-stimulated BV
      2 microglia cells. PDTC altogether abolished LPS-induced nuclear translocation of
      HIF-3alpha with a partial effect on HIF-1alpha, suggesting that HIF-3alpha
      expression under inflammatory conditions may be directly under the control of the
      NF-kappaB pathway in BV-2 microglial cells. Interestingly, HIF-3alpha and HIF
      1alpha exhibited almost similar responses to a variety of activating or
      inhibiting pharmacological agents. These results provide the first evidence for
      regulation of HIF-3alpha under inflammatory conditions in BV-2 microglial cells.

PMID- 25847717
TI  - Brain mechanisms of pain relief by transcutaneous electrical nerve stimulation: A
      functional magnetic resonance imaging study.
AB  - BACKGROUND: Although the exact mechanism of TENS pain relief is unknown, it is
      believed that TENS impulses interrupt nociceptive signals at the dorsal horn of
      the spinal cord. AIMS: To evaluate the hypotheses that during pain caused by
      noxious stimuli, brain responses, temporal summation and brain functional
      connectivity are modulated by TENS, and that mechanisms of pain relief by TENS
      differ between men and women. METHODS: During fMRI scanning, the same noxious
      stimuli were delivered to each participant in pain-only and pain+TENS conditions.
      In the pain-only condition, noxious stimuli were presented without TENS. In the
      pain+TENS condition, participants received noxious stimuli and TENS concurrently.
      Participants were initially presented with TENS at an intensity that was just
      below that causing discomfort. TENS intensity was presented in a step-wise
      fashion to prevent temporal summation from repetitive noxious stimuli. RESULTS:
      Pain and unpleasantness ratings were significantly higher in the pain-only than
      the pain+TENS condition. With non-painful TENS, primary and secondary
      somatosensory and parietal cortices were activated, and temporal summation from
      repetitive noxious stimuli was prevented. Periaqueductal gray (PAG) and lateral
      prefrontal cortex functional connectivity was increased by TENS, and modulated by
      testosterone and cortisol. Women reported greater pain during TENS than men, and
      showed greater activation in the temporoparietal junction cortex and increased
      PAG functional connectivity with the orbitofrontal cortex. CONCLUSION: TENS led
      to pain reduction, probably due to activation of the descending pain-inhibitory
      pathway, indicating that this TENS method may be applied in clinical practice.

PMID- 25847718
TI  - Ten years of science news: A longitudinal analysis of scientific culture in the
      Spanish digital press.
AB  - This article presents our study of science coverage in the digital Spanish press
      over the last decade. We employed automated information retrieval procedures to
      create a corpus of 50,763 text units dealing with science and technology, and
      used automated text-analysis procedures in order to provide a general picture of
      the structure, characteristics and evolution of science news in Spain. We found
      between 6% and 7% of science coverage, a clear high proportion of biomedicine and
      predominance of science over technology, although we also detected an increase in
      technological content during the second half of the decade. Analysing the
      extrinsic and intrinsic features of science culture, we found a predominance of
      intrinsic features that still need further analysis. Our attempt to use
      specialised software to examine big data was effective, and allowed us to reach
      these preliminary conclusions.

PMID- 25847719
TI  - How certain is 'certain'? Exploring how the English-language media reported the
      use of calibrated language in the Intergovernmental Panel on Climate Change's
      Fifth Assessment Report.
AB  - This article presents findings from an analysis of English-language media reports
      following the publication of the fifth Intergovernmental Panel on Climate Change
      Assessment Report in September 2013. Focusing on the way they reported the
      Intergovernmental Panel on Climate Change's use of 'calibrated' language, we find
      that of 1906 articles relating to the issuing of the report only 272 articles
      (14.27%) convey the use of a deliberate and systematic verbal scale. The
      Intergovernmental Panel on Climate Change's carefully calibrated language was
      rarely discussed or explicated, but in some instances scientists, political
      actors or journalists would attempt to contextualise or elaborate on the reported
      findings by using analogies to other scientific principles or examples of taking
      action despite uncertainty. We consider those analogies in terms of their
      efficacy in communicating (un)certainty.

PMID- 25847720
TI  - EPSPS gene amplification in glyphosate-resistant Bromus diandrus.
AB  - BACKGROUND: Glyphosate is the most widely used herbicide in the world and has
      been intensively used to control B. diandrus, a problematic weed of crops and
      pastures in southern Australia. RESULTS: Resistance to glyphosate was identified
      in two populations of B. diandrus that were nearly fivefold more resistant to
      glyphosate than wild-type plants. Both populations contained EPSPS gene
      amplification, with resistant plants having an average of around 20-fold the
      number of copies of EPSPS compared with susceptible plants. EPSPS expression was
      also increased in resistant plants of both populations; however, expression
      levels were not correlated with the number of EPSPS copies. Amplification of only
      one of the four EPSPS genes present in B. diandus was detected. Investigation
      into the inheritance of glyphosate resistance found no segregation in the F2
      generation. Every individual in the F2 populations contained between three and 30
      copies of EPSPS; however, on average they contained fewer copies compared with
      the parent resistant population. CONCLUSIONS: Glyphosate resistance in B.
      diandrus is due to EPSPS gene amplification. Resistance is heritable but complex.

PMID- 25847721
TI  - Clinical outcomes and histological findings of patients with advanced metastatic
      germ cell tumors undergoing post-chemotherapy resection of retroperitoneal lymph
      nodes and residual extraretroperitoneal masses.
AB  - OBJECTIVES: To assess clinical outcomes of patients with advanced germ cell tumor
      undergoing post-chemotherapy retroperitoneal lymph node dissection with or
      without extraretroperitoneal mass resection. METHODS: Between 1998 and 2013, 175
      retroperitoneal lymph node dissections for advanced metastatic germ cell tumors
      were carried out at Kyoto Prefectural University of Medicine, Kyoto, Japan. Of
      patients receiving retroperitoneal lymph node dissections, 156 underwent post
      chemotherapy retroperitoneal lymph node dissection with or without
      extraretroperitoneal mass resection as first surgery after completion of
      chemotherapy. Of these 156 patients, 47 underwent both post-chemotherapy
      retroperitoneal lymph node dissection and extraretroperitoneal mass resection.
      RESULTS: The histological findings were necrosis in 59.6%, teratoma in 31.4% and
      viable cancer in 9.0% at retroperitoneal lymph node. At extraretroperitoneal mass
      resection, necrosis was present in 59.6%, teratoma in 31.9% and viable cancer in
      8.5%. Overall histological discordance between retroperitoneal lymph node and
      extraretroperitoneal mass was found in 31.9%. Five-year disease-free survival
      stratified by retroperitoneal lymph node histology in 156 patients was 91.3% for
      necrosis, 78.7% for teratoma and 63.5% for viable cancer (log-rank, P = 0.009).
      Antegrade ejaculation was preserved in 80.9%. In the worst histology of post
      chemotherapy retroperitoneal lymph node dissection or extraretroperitoneal mass
      resection in 156 patients, 5-year disease-free survival was 93.2% for necrosis,
      79.0% for teratoma and 63.4% for viable cancer (log-rank, P < 0.001). Independent
      prognostic factors for disease-free survival were presence of viable cancer in
      retroperitoneal lymph node histology and salvage chemotherapy. CONCLUSION: The
      presence of viable cancer at the retroperitoneal lymph node is an independent
      predictor of disease recurrence. In approximately one-third of cases, there is a
      histological discordance between retroperitoneal lymph node and
      extraretroperitoneal mass. Resection of residual retroperitoneal lymph node and
      extraretroperitoneal masses remains an important procedure in the management of
      advanced germ cell tumors.

PMID- 25847722
TI  - Comparison of the clinical and functional outcomes following 3- and 4-corner
      fusions.
AB  - PURPOSE: To explore the clinical and functional outcomes of 3-corner fusion (3CF)
      for stage 2 and 3 scapholunate advanced collapse and scaphoid nonunion advanced
      collapse. We compared the results with 4-corner fusion (4CF) using a recent
      published report. METHODS: Twelve patients (8 men and 4 women) who had a 3CF,
      mean age 60 years (range, 34-75 y) were reviewed in clinic more than 1 year after
      surgery. Subjective outcome measures included the Michigan Hand Questionnaire and
      Patient Evaluation Measure. Objective outcome measures included range of motion
      with a flexible electrogoniometer and grip strength measured with a digital
      dynamometer. The results were compared using a recent report of 24 patients (17
      men and 7 women) with a 4CF, mean age 55 years (range, 34-68 y) assessed with
      similar techniques. RESULTS: The patients receiving 3CF had better subjective
      scores with the Michigan Hand Questionnaire, including the sub-scores for
      activities of daily living and satisfaction. The radioulnar arc was greater after
      the 3CF than after the 4CF. Circumduction of the 3CF was more like a normal wrist
      than the 4CF. This included having faster and smoother motion, with an axis of
      circumduction closer to the normal wrist. Peak grip strength was similar after
      either a 3CF or 4CF but grip strength in the 3CF was 82% of the contralateral
      wrist compared with 59% for the 4CF. CONCLUSIONS: The 3CF provided better patient
      rated scores and the arc of wrist motion was more extended, with greater ulnar
      deviation. Motion was smoother and more closely replicated the normal axis and
      functional motion of the wrist. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic III.

PMID- 25847723
TI  - Contributions of muscle imbalance and impaired growth to postural and osseous
      shoulder deformity following brachial plexus birth palsy: a computational
      simulation analysis.
AB  - PURPOSE: Two potential mechanisms leading to postural and osseous shoulder
      deformity after brachial plexus birth palsy are muscle imbalance between
      functioning internal rotators and paralyzed external rotators and impaired
      longitudinal growth of paralyzed muscles. Our goal was to evaluate the combined
      and isolated effects of these 2 mechanisms on transverse plane shoulder forces
      using a computational model of C5-6 brachial plexus injury. METHODS: We modeled a
      C5-6 injury using a computational musculoskeletal upper limb model. Muscles
      expected to be denervated by C5-6 injury were classified as affected, with the
      remaining shoulder muscles classified as unaffected. To model muscle imbalance,
      affected muscles were given no resting tone whereas unaffected muscles were given
      resting tone at 30% of maximal activation. To model impaired growth, affected
      muscles were reduced in length by 30% compared with normal whereas unaffected
      muscles remained normal in length. Four scenarios were simulated: normal, muscle
      imbalance only, impaired growth only, and both muscle imbalance and impaired
      growth. Passive shoulder rotation range of motion and glenohumeral joint reaction
      forces were evaluated to assess postural and osseous deformity. RESULTS: All
      impaired scenarios exhibited restricted range of motion and increased and
      posteriorly directed compressive glenohumeral joint forces. Individually,
      impaired muscle growth caused worse restriction in range of motion and higher and
      more posteriorly directed glenohumeral forces than did muscle imbalance. Combined
      muscle imbalance and impaired growth caused the most restricted joint range of
      motion and the highest joint reaction force of all scenarios. CONCLUSIONS: Both
      muscle imbalance and impaired longitudinal growth contributed to range of motion
      and force changes consistent with clinically observed deformity, although the
      most substantial effects resulted from impaired muscle growth. CLINICAL
      RELEVANCE: Simulations suggest that treatment strategies emphasizing treatment of
      impaired longitudinal growth are warranted for reducing deformity after brachial
      plexus birth palsy.

PMID- 25847724
TI  - The validity and acceptability of a text-based monitoring system for pediatric
      asthma studies.
AB  - A meaningful analysis in research requires robust, valid data. Paper diaries
      allow the collection of data from individuals over time but are notorious for
      poor compliance and validity. SMS-technology is a novel method for data
      collection in medical research. Time-tagged SMS are transferred directly to an
      electronic file. We used SMS to collect symptoms and peak flow rate (PEFR) meter
      readings from 32 children with asthma. Parents responded first to five SMS daily
      for 7 days during an asymptomatic period and then for 14 days during a cold.
      Compliance with use of PEFR meter and SMS system were assessed. Digital PEFR
      meters enabled data download at the end of the study to confirm validity of
      transmitted data. Parents of 24 participants provided feedback about this data
      collection tool. Mean (+/-SD) "SMS-diary and PEFR-meter compliance" were 96% (+/
      8) and 84% (+/-21) during baseline and 91% (+/-12) and 82% (+/-20) during cold
      respectively. Correctly reported PEFR values were found in 65.5% of all cases, in
      8.3% PEFR values sent were "self-invented" and 2.4% of values were missing. All
      of the 22 parents completing the baseline questionnaire were happy to use SMS for
      this study. Of the 20 parents completing the follow up questionnaire, 95% (19/20)
      found the system user-friendly, 55% (11/20) would be more likely to participate
      in studies if they were using SMS data collection and 25% (5/20) were "sometimes
      unhappy" about receiving messages. This real-time capture of data is well
      accepted and could avoid some of the pitfalls of backfilled paper diaries.

PMID- 25847725
TI  - Differential improvement of vertical and horizontal metamorphopsia scores after
      epiretinal membrane vitrectomy with ILM peeling.

PMID- 25847726
TI  - Advances in experimental systems to study hepatitis C virus in vitro and in vivo.
AB  - Hepatitis C virus (HCV) represents a global health concern affecting over 185
      million people worldwide. Chronic HCV infection causes liver fibrosis and
      cirrhosis and is the leading indication for liver transplantation. Recent
      advances in the field of direct-acting antiviral drugs (DAAs) promise a cure for
      HCV in over 90% of cases that will get access to these expensive treatments.
      Nevertheless, the lack of a protective vaccine and likely emergence of drug
      resistant viral variants call for further studies of HCV biology. With
      chimpanzees being for a long time the only non-human in vivo model of HCV
      infection, strong efforts were put into establishing in vitro experimental
      systems. The initial models only enabled to study specific aspects of the HCV
      life cycle, such as viral replication with the subgenomic replicon and entry
      using HCV pseudotyped particles (HCVpp). Subsequent development of protocols to
      grow infectious HCV particles in cell-culture (HCVcc) ignited investigations on
      the full cycle of HCV infection and the virus-host interactions required for
      virus propagation. More recently, small animal models permissive to HCV were
      generated that allowed in vivo testing of novel antiviral therapies as well as
      vaccine candidates. This review provides an overview of the currently available
      in vitro and in vivo experimental systems to study HCV biology. Particular
      emphasis is given to how these model systems furthered our understanding of virus
      host interactions, viral pathogenesis and immunological responses to HCV
      infection, as well as drug and vaccine development. 

PMID- 25847727
TI  - Surgical treatment options for aggressive osteoblastoma in the mobile spine.
AB  - PURPOSE: Osteoblastoma (OBL) is a benign bone tumor with considerable recurrence
      potential. Resection is the mainstay for the treatment of Enneking stage 3 (st.
      3) OBL. This retrospective study aimed to verify the appropriate surgical
      strategy for st. 3 lesions in the mobile spine. METHODS: 19 cases of st. 3 OBL
      was diagnosed between 2001 and 2011. Clinical, radiological, surgical, and follow
      up data were analyzed. This series included 14 men and 5 women and the mean age
      at diagnosis was 30.4 years. The lesions were located in the cervical spine in
      ten cases, in the thoracic spine in eight, and in the lumbar spine in one.
      Fourteen patients were surgically treated for the first time (intact cases), and
      five were referred to us after previous unsuccessful treatments (non-intact
      cases). RESULTS: Before 2008, 11 patients underwent curettage followed by
      radiotherapy, including 5 non-intact cases and 6 intact cases. Tumor recurrence
      was observed in all five non-intact cases and four of the six intact cases. After
      2008, eight intact patients underwent intralesional vertebrectomy, including six
      who underwent piecemeal total vertebrectomy and two who underwent intralesional
      en bloc vertebrectomy. All the eight patients had embolization before surgery. 18
      patients had an average 67.3 months (range 36-148 months) of follow-up.
      Recurrence was not observed in any of these eight cases with intralesional
      vertebrectomy. CONCLUSION: Intralesional total vertebrectomy might be an
      appropriate choice for intact st. 3 OBL spine lesions. More cases with longer
      follow-up periods should be recruited in the future to better understand the
      treatment options available for this disease.

PMID- 25847728
TI  - Neck range of motion measurements using a new three-dimensional motion analysis
      system: validity and repeatability.
AB  - PURPOSE: Neck movement is important for many activities of daily living (ADL).
      Neck disorders, such as cervical spondylosis and whiplash can limit neck movement
      and ADL. The cervical range of motion (CROM) device has been recently used to
      measure neck range of motion (ROM); however, this measurement includes trunk
      motion, and therefore does not represent a pure neck ROM measurement. The authors
      aimed to develop a new method to establish pure neck ROM measurements during
      flexion, extension, lateral bending, and rotation using a three-dimensional
      motion analysis system, VICON. METHODS: Twelve healthy participants were
      recruited and neck ROMs during flexion, extension, lateral bending, and rotation
      were measured using VICON and the CROM device. Test-retest repeatability was
      assessed using interclass correlation coefficients (ICCs), standard error of
      measurement (SEM), and minimal detectable change (MDC). Validity between two
      measurements was evaluated using a determination coefficient and Pearson's
      correlation coefficient. RESULTS: ICCs of neck ROM measured using VICON and the
      CROM device were all at substantial or almost perfect levels [VICON: ICC(1,2) =
      0.786-0.962, the CROM device: ICC(1,2) = 0.736-0.950]. Both SEMs and MDCs were
      low in all measurement directions (VICON: SEM = 1.3 degrees -4.5 degrees , MDC =
      3.6 degrees -12.5 degrees ; the CROM device: SEM = 2.2 degrees -3.9 degrees , MDC
      = 6.1 degrees -10.7 degrees ). Determination coefficients (R(2)s) and Pearson's
      correlation coefficients (rs) between the two measurement methods were high (R(2)
      = 0.607-0.745, r = 0.779-0.863). CONCLUSIONS: VICON is a useful system to measure
      neck ROMs and evaluate the efficacy of interventions, such as surgery or
      physiotherapeutic exercise.

PMID- 25847729
TI  - The fate of adjacent segments with pre-existing degeneration after lumbar
      posterolateral fusion: the influence of degenerative grading.
AB  - PURPOSE: To evaluate the impact of pre-existing disc degeneration and its extent
      on future adjacent segment degeneration (ASDeg) after lumbar posterolateral
      fusion (PLF). METHODS: A total of 102 patients who had undergone PLF for
      degenerative lumbar diseases from January 2006 to December 2008 were
      retrospectively reviewed by using radiography and clinical evaluation. The
      University of California at Los Angeles (UCLA) grading scale was used to evaluate
      the extent of disc degeneration. The Visual Analog Scale, Oswestry Disability
      Index, and SF-36 questionnaire were used to evaluate clinical outcomes. RESULTS:
      The overall prevalence of radiological ASDeg was 25.5 %, and the prevalence of
      ASDeg for the cranial and caudal levels was 19.6 and 15.1 %, respectively. The
      prevalence of ASDeg in one-, two-, and three-level fusion was 15.8, 26.3, and 50
      %, respectively (p = 0.008). For the cranial level, the preoperative UCLA grade
      A, B, and C groups had prevalence values for ASDeg of 13.5, 28.6, and 42.9 %,
      respectively (p = 0.026). A higher prevalence of ASDeg was found in cranial discs
      with pre-existing degeneration than in the group without pre-existing
      degeneration (p = 0.012). The group without pre-existing degeneration showed
      better outcomes. For the caudal level, there was no significant difference in
      ASDeg prevalence. At final follow-up, the group without pre-existing disc
      degeneration showed better outcomes than the group with pre-existing disc
      degeneration. CONCLUSIONS: Adjacent segment discs with pre-existing degeneration
      had a higher likelihood of ASDeg progression compared with normal discs,
      especially for those classified as UCLA grade C.

PMID- 25847730
TI  - Clinical value of liver ultrasound for the diagnosis of nonalcoholic fatty liver
      disease in overweight and obese patients.
AB  - BACKGROUND & AIMS: Liver ultrasound (US) is usually used in the clinical setting
      for the diagnosis and follow-up of patients with nonalcoholic fatty liver disease
      (NAFLD). However, no large study has carefully assessed its performance using a
      semiquantitative ultrasonographic scoring system in overweight/obese patients, in
      comparison to magnetic resonance spectroscopy ((1) H-MRS) and histology. METHODS:
      We recruited 146 patients and performed: a liver US using a 5-parameter scoring
      system, a liver (1) H-MRS to quantify liver fat content, and a liver biopsy to
      assess histology. All measurements were repeated in a subgroup of patients (n =
      62) after 18 months of follow-up. RESULTS: The performance of liver US
      (parenchymal echo alone) was rather modest, and significantly worse than (1) H
      MRS (AUROC: 0.82 [0.69-0.94] vs. 0.96 [0.90-1.00]; P = 0.04). However, the AUROC
      improved when different echographic parameters were taken into account (AUROC:
      0.89 [0.83-0.96], P = 0.15 against (1) H-MRS). Optimum sensitivity for liver US
      was achieved at a liver fat content >=12.5%, suggesting that below this
      threshold, liver US is less sensitive. Liver (1) H-MRS showed a high accuracy for
      the diagnosis of NAFLD, and correlated strongly with histological steatosis (r =
      0.73, P < 0.0001). None of the imaging tests was adequate enough to predict
      changes over time in histology. CONCLUSIONS: Despite its widespread use, liver US
      has several important limitations that healthcare providers should recognize,
      particularly because of its low sensitivity. Using a combination of echographic
      parameters, liver US showed a significant improvement in its diagnostic
      performance, but still was of limited value for monitoring treatment over time.

PMID- 25847731
TI  - Antioxidant-mediated reversal of oxidative damage in mouse modeling of complex I
      inhibition.
AB  - Mitochondrial dysfunction is a key component of various aging-related pathologies
      of the brain that result in dementia. As such, it provides an important avenue in
      development of therapeutic interventions for a host of neurological disorders. A
      requirement for functional mitochondrial respiratory chain complex I (CI), to
      accomplish the normal physiological processes regulating memory, seems intuitive.
      In the present study, a synthetic lipoylcarnitine antioxidant (PMX-500FI; 100
      mg/kg/day po) was administered to female ICR mice (3-4-month old) that were
      subsequently treated with the mitochondrial CI inhibitor, rotenone (400
      mg/kg/day). After 1 week, rotenone-induced impairment of neuronal function was
      evaluated in the hippocampus, a brain region that is involved in regulating
      memory formation. Electrophysiological recordings in live brain slices showed
      that long-term potentiation (LTP) was reduced by rotenone exposure (P < 0.05)
      while pretreatment with PMX-500FI maintained LTP similar to control levels (P >
      0.05). Potentiation during theta burst stimulation (TBS) was similar among
      treatment groups (P > 0.05); however, neurotransmitter release, which increased
      in control mice after TBS, was lower in rotenone treated mice (P < 0.05), and was
      accompanied by reduced basal synaptic transmission (P < 0.05), increased
      proapoptotic signaling and decreased extracellular signal-regulated kinase1/2
      (ERK1/2) phosphorylation (P < 0.05). For each of these determinations,
      pretreatment with PMX-500FI alleviated the harmful effects of rotenone. These
      results illustrate that treatment with antioxidant PMX-500FI is protective
      against rotenone-induced impairment of neuronal bioenergetics in the mouse
      hippocampus, in regard to both excitatory synaptic physiology and proapoptotic
      signaling. The protective effect of PMX-500FI against rotenone-induced disruption
      of cellular bioenergetics may have important therapeutic implications for
      treating aging-related dementia and other diseases related to mitochondrial
      dysfunction and/or oxidative damage.

PMID- 25847732
TI  - Fruit and vegetable consumption and food values: National patterns in the United
      States by Supplemental Nutrition Assistance Program eligibility and cooking
      frequency.
AB  - BACKGROUND: More frequent cooking at home may help improve diet quality and be
      associated with food values, particularly for individuals participating in the
      Supplemental Nutrition Assistance Program (SNAP). OBJECTIVE: To examine patterns
      of fruit and vegetable consumption and food values among adults (aged 20 and
      older) in the United States, by SNAP participation and household cooking
      frequency. METHODS: Analysis of cross-sectional 24-hour dietary recall data
      obtained from the National Health and Nutrition Examination Survey 2007-2010
      (N=9560). RESULTS: A lower percentage of SNAP participants consumed fruit (total:
      35% vs. 46%, p=0.001; fresh: 30% vs. 41%, p<0.001) and vegetables (total: 49% vs.
      58%, p=0.004; fresh: 35% vs. 47%, p<0.001) than those ineligible for SNAP. Among
      SNAP participants, cooking >6times/week was associated with greater vegetable
      consumption compared to cooking <2times/week (175g vs. 98g, p=0.003). SNAP
      eligible individuals who cooked >=2times/week were more to report price (medium
      cookers: 47% vs. 33%, p=0.001; high cookers: 52% vs. 40%, p<0.001), ease of
      preparation (medium cookers: 36% vs. 28%, p=0.002; high cookers: 36% vs. 24%,
      p<0.001) and how long food keeps (medium cookers: 57% vs. 45%, p<0.001; high
      cookers: 61% vs. 50%, p<0.001) as important compared to SNAP-ineligible
      individuals. CONCLUSIONS: Fruit and vegetable consumption in the United States is
      low regardless of cooking frequency. Efforts to improve diet quality should
      consider values on which food purchases are based.

PMID- 25847733
TI  - Rapid in vivo multicomponent T2 mapping of human knee menisci.
AB  - PURPOSE: To compare multicomponent T2 parameters of menisci measured using
      Multicomponent Driven Equilibrium Single Pulse Observation of T1 and T2
      (mcDESPOT) in asymptomatic volunteers and osteoarthritis (OA) patients with
      intact and torn menisci. MATERIALS AND METHODS: The prospective study was
      performed with Institutional Review Board approval and with all subjects signing
      written informed consent. mcDESPOT was performed on the knee joint of 12
      asymptomatic volunteers and 14 patients with knee OA. Single-component T2
      relaxation time (T2Single ), T2 relaxation time of the fast relaxing water
      component (T2F ), and the slow relaxing water component (T2S ), and fraction of
      the fast relaxing water component (FF ) of the medial and lateral menisci were
      measured. Multivariate linear regression models were used to compare mcDESPOT
      parameters between normal menisci in asymptomatic volunteers, intact menisci in
      OA patients, and torn menisci in OA patients with adjustment for differences in
      age between subjects. RESULTS: The mean mcDESPOT parameters for normal menisci in
      asymptomatic volunteers, intact menisci in OA patients, and torn menisci in OA
      patients were respectively 16.1 msec, 18.8 msec, and 22.7 msec for T2Single ; 9.0
      msec, 10.0 msec, and 11.1 msec for T2F ; 24.4 msec, 27.7 msec, and 31.4 msec for
      T2S ; and 34%, 32%, 27% for FF . There were significant differences (P < 0.05) in
      T2Single , T2F , T2S , and FF between the three groups of menisci. CONCLUSION:
      The menisci of OA patients had significantly higher T2Single , T2F , and T2S and
      significantly lower FF than normal menisci in asymptomatic volunteers with
      greater changes in multicomponent T2 parameters noted in torn than intact menisci
      in OA patients.

PMID- 25847734
TI  - Improving multivariable prostate cancer risk assessment using the Prostate Health
      Index.
AB  - OBJECTIVES: To analyse the clinical utility of a prediction model incorporating
      both clinical information and a novel biomarker, p2PSA, in order to inform the
      decision for prostate biopsy in an Irish cohort of men referred for prostate
      cancer assessment. PATIENTS AND METHODS: Serum isolated from 250 men from three
      tertiary referral centres with pre-biopsy blood draws was analysed for total
      prostate-specific antigen (PSA), free PSA (fPSA) and p2PSA. From this, the
      Prostate Health Index (PHI) score was calculated (PHI = (p2PSA/fPSA)*?tPSA). The
      men's clinical information was used to derive their risk according to the
      Prostate Cancer Prevention Trial (PCPT) risk model. Two clinical prediction
      models were created via multivariable regression consisting of age, family
      history, abnormality on digital rectal examination, previous negative biopsy and
      either PSA or PHI score, respectively. Calibration plots, receiver-operating
      characteristic (ROC) curves and decision curves were generated to assess the
      performance of the three models. RESULTS: The PSA model and PHI model were both
      well calibrated in this cohort, with the PHI model showing the best correlation
      between predicted probabilities and actual outcome. The areas under the ROC curve
      for the PHI model, PSA model and PCPT model were 0.77, 0.71 and 0.69,
      respectively, for the prediction of prostate cancer (PCa) and 0.79, 0.72 and
      0.72, respectively, for the prediction of high grade PCa. Decision-curve analysis
      showed a superior net benefit of the PHI model over both the PSA model and the
      PCPT risk model in the diagnosis of PCa and high grade PCa over the entire range
      of risk probabilities. CONCLUSION: A logical and standardized approach to the use
      of clinical risk factors can allow more accurate risk stratification of men under
      investigation for PCa. The measurement of p2PSA and the integration of this
      biomarker into a clinical prediction model can further increase the accuracy of
      risk stratification, helping to better inform the decision for prostate biopsy in
      a referral population.

PMID- 25847735
TI  - [Is there a place for thrombin generation assay in routine clinical laboratory?].
AB  - Laboratory diagnosis of coagulopathies primarily relies on assays selectively
      exploring either the extrinsic (PT), the intrinsic (aPTT) or the common (TT)
      pathway of the coagulation system. Although these tests are very useful to
      rapidly identify severe coagulation disorders or to monitor anticoagulant
      therapy, they only poorly correlate with the clinical manifestations. Global
      assays that evaluate the whole coagulation process could potentially more
      accurately reflect the hemorrhagic or thrombotic phenotype of an individual.
      Thrombin generation assay (TGA), first described in the 1950's, has been
      developed and automated in the 1990's. This technique is widely used in
      fundamental research but has yet failed to integrate clinical laboratories. In
      this article, we describe TGA and review its clinical applications. Laboratory
      aspects and technical issues will also be discussed. 

PMID- 25847736
TI  - [Urinary biomarkers of kidney dysfunction].
AB  - The early diagnosis of chronic kidney disease (CKD) is based on the detection of
      markers of renal damage in urine collection. These urinary bio-markers are
      measurable before the appearance of functional defect, which is diagnosed with a
      decrease of glomerular filtration rate. Albuminuria, preferentially expressed as
      urinary albumin/creatinin ratio, is one of the marker of CKD. But today, other
      urinary biomarkers, monitoring tubulointersticial damage, are of interest in
      early diagnosis of CKD. In acute kidney injury, these markers could improve
      diagnostic tests, since they increase faster than serum creatinin. We propose a
      review of the urinary biomarkers of renal dysfunction used in routine clinical
      practice in 2015. 

PMID- 25847737
TI  - [Accumulation of p53 protein and overexpression of the HER3 receptor in
      colorectal cancer].
AB  - In patients with colorectal cancer, nuclear accumulation of p53 is often
      associated with poor prognosis and resistance to chemotherapy. Overexpression of
      HER3 is associated with poor prognosis and resistance to therapy targeting EGFR.
      Our study was performed on 16 samples of colorectal adenocarcinomas. The pieces
      fixed in formalin were embedded in paraffin. The study of the expression of p53
      and HER3 is performed by immunohistochemical technique. Immunohistochemical study
      of the expression of p53 showed nuclear accumulation of this protein in 87% of
      colorectal adenocarcinomas analyzed. Regarding the HER3 receptor overexpression
      was observed in 56% of cases. Overall, 50% of the cases co-expressed p53 and
      HER3. HER3 and p53 are important markers of colorectal cancer because they
      provide information about the distinctive biological characteristics of tumors.
      The prognostic and predictive value of the combination of these two markers could
      be an important clinical tool. 

PMID- 25847738
TI  - [External quality assessment in clinical biochemistry laboratories: pilot study
      in 11 laboratories of Lome (Togo)].
AB  - This study aims to evaluate the performance of a few biochemistry analysis and
      make recommendations to the place of the stakeholders. It is a cross-sectional
      study conducted between the October 1(st), 2012 and the July 31, 2013 bearing on
      the results of 5 common examinations of clinical biochemistry, provided by 11
      laboratories volunteers opening in the public and private sectors. These
      laboratories have analysed during the 3 cycles, 2 levels (medium and high) of
      serum concentration of urea, glucose, creatinine and serum aminotransferases. The
      performance of laboratories have been determined from the acceptable limits
      corresponding to the limits of total errors, defined by the French Society of
      Clinical Biology (SFBC). A system of internal quality control is implemented by
      all laboratories and 45% of them participated in international programs of
      external quality assessment (EQA). The rate of acceptable results for the entire
      study was of 69%. There was a significant difference (p<0.002) between the
      performance of the group of laboratories engaged in a quality approach and the
      group with default implementation of the quality approach. Also a significant
      difference was observed between the laboratories of the central level and those
      of the peripheral level of our health system (p<0.047). The performance of the
      results provided by the laboratories remains relatively unsatisfactory. It is
      important that the Ministry of Health put in place a national program of EQA with
      mandatory participation.

PMID- 25847740
TI  - Autosomal dominant polycystic kidney disease: identification of two
      polymorphisms.
AB  - The identification of polymorphism A4059V associated with the 12276 A>G at exon
      45 of the PKD1 gene in a Tunisian polycystic patient. 

PMID- 25847739
TI  - [Antimicrobial activity of Actinomycetale isolated from the lagoon in Algeria].
AB  - In the aim of the study of the taxonomy and the antimicrobial activity, a strain
      of actinomycete SM2/2GF which was isolated from sediment of the lagoon El-Mellah
      which is situated in the city of El-Kala in the Northeast of Algeria, was tested
      against diverse pathogenic microorganisms and against a Gram-negative bacterium
      Pseudomonas alcaliphila which was isolated from water of the lagoon El-Mellah.
      The phenotypic and the molecular characteristics show that the isolate SM2/2GF
      belongs to the kind Streptomyces. This strain showed an antimicrobial activity
      against a Gram-negative bacterium Pseudomonas alcaliphila and the positive-Gram
      bacteria as Staphylococcus aureus, methicillin-resistant Staphylococcus aureus
      (MRSA), Bacillus subtilis, Enterococcus faecalis, as well as the yeast Candida
      albicans. It has no activity against Pseudomonas aeruginosa. The interesting
      antimicrobial activity of the strain SM2/2GF against the pathogenic
      microorganisms could encourage further researches on one or several bioactive
      molecules which it secretes.

PMID- 25847741
TI  - [An acute monoclonal gammopathy?].
AB  - Serum protein electrophoresis is commonly used in case of acute or chronic renal
      failure. It can lead to the etiologic diagnosis by detecting monoclonal
      gammopathies which are frequently complicated by renal failure, such as cast
      nephropathy, Randall's disease or amyloidosis, or to explore an associated
      inflammatory syndrome. We report the occurrence of two monoclonal components in a
      patient without any monoclonal component 10 days earlier. The sudden appearance
      of these two monoclonal components associated to the context of sepsis of urinary
      origin suggested the diagnosis of transient monoclonal gammopathy. This
      hypothesis was confirmed by monitoring serum protein electrophoresis that showed
      a gradual decrease of these two monoclonal components few weeks after the
      resolution of the infectious disease. The main etiological factors of transient
      monoclonal gammopathies are infectious or autoimmune diseases. In this context,
      it is important to delay the achievement of serum protein electrophoresis after
      the acute episode, in order to avoid to falsely conclude to hematologic
      malignancy diagnosis. This can prevent costly biological examinations of these
      transient monoclonal gammopathies and invasive procedures like bone marrow
      examination. 

PMID- 25847743
TI  - [Prolonged molecular response induced by imatinib in Philadelphia positive acute
      lymphoblastic leukemia A case report and brief review].
AB  - Philadelphia or BCR-ABL positive acute lymphoblastic leukemia (PH+ ALL) is the
      most common and severe of adult ALL. The only potentially curator treatment
      remains allogeneic hematopoietic stem cells transplantation (SCT) in first
      complete remission. The use of imatinib has revolutionized the treatment of
      chronic myeloid leukemia. Its incorporation into PH + ALL protocols also improved
      the prognosis of this disease giving better complete remission rates compared to
      chemotherapy alone. The treatment of patients not eligible for SCT remains
      controversial. Prolonged use of high dose tyrosine kinase inhibitors (TKI) (ie:
      imatinib at 600 or 800 mg/j) as maintenance therapy seems to be a reasonable
      approach. We present a case of prolonged molecular remission of PH+ ALL under TKI
      alone as maintenance therapy.

PMID- 25847742
TI  - [A case of bisalbuminemia in a patient with digestive adenocarcinoma].
AB  - Bisalbuminemia whether hereditary or acquired, is a rare electrophoretic
      abnormality of albumin, characterized by a duplication of the albumin fraction on
      the electrophoretic trace of the serum proteins. This duplication reflects the
      presence in the same individual normal plasma albumin and a modified albumin.
      OBSERVATION: This is a patient of 62 years hospitalized at the Internal Medicine
      Department of HMIMV for liver metastases of gastrointestinal adenocarcinoma and
      including serum protein electrophoresis (EP) performed on capillary (Capillarys
      society Sebia) reveals bisalbuminemia. The family investigation has ruled that
      inheritance of acquired bisalbuminemia to retain appearance. COMMENT:
      Bisalbuminemia acquired outside treatment with high doses of beta-lactam
      antibiotics, chronic pancreatitis with pseudocyst rupture or fixing a monoclonal
      immunoglobulin on albumin in the myeloma subjects is an exceptional event. The
      pathophysiologic mechanism in the reported cases remains unexplained as is also
      the case of acquired bisalbuminemias associated with other pathological contexts
      (Alzheimer's disease nephrotic syndrome). CONCLUSION: To the best of our
      knowledge, the bisalbuminemia in the gastrointestinal adenocarcinoma liver
      metastases has not been reported to date, hence the importance of the reported
      cases.

PMID- 25847744
TI  - [Free thyroxine immunoassay: analytical review].
AB  - Thyroid hormones assays (T4 and T3) are limited to the free forms with hormonal
      activity, the only ones useful for the assessment of thyroid function. Free
      thyroxine assays are part of prescribed parameters by the physician once known
      plasma TSH concentration. A reference method exists, but immunoassays are the
      most commonly technics used in current practice. After a reminder of the
      iodothyronine biochemistry and physiology, the authors discuss preanalytical and
      analytical steps in detail, focusing on the possible pitfalls. 

PMID- 25847745
TI  - [Immunoanalytical profile of free tri-iodothyronine].
AB  - Tri-iodothyronine (T3) is the active form of thyroid hormone at the nuclear cell
      level. About 80% of tri-iodothyronine is produced by peripheral deiodination of
      thyroxine. The determination of the free form of this hormone is useful for the
      diagnosis and the follow-up of hyperthyroidism. In routine clinical laboratories,
      immunoassays remain the most used technics. After recalling the main points
      related to the physiological data, the authors point out the possible errors
      during the analytical steps of the assay. 

PMID- 25847746
TI  - [TSH-receptor antibodies: immunoanalytical characteristics].
AB  - Besides the main biochemical characteristics of anti TSH-receptor antibodies,
      this paper points out the optimal conditions for their assays and the
      interpretation of results. 

PMID- 25847747
TI  - [Guidelines for certification of Activated clotting time (ACT) according to the
      EN ISO 22870 standards].
AB  - Point of care testing (POCT) must comply with regulatory requirements according
      to standard EN ISO 22870, which identify biologists as responsible for POCT.
      Activated clotting time (ACT) is mandatory to monitor on whole blood,
      anticoagulation achieved by unfractionated heparin during cardiopulmonary bypass
      (CPB) or cardiac catheterization. This test has no equivalent in the laboratory.
      With the aim to help the multidisciplinary groups for POCT supervision when they
      have to analyse the wish of medical departments to use ACT and to help the
      biologists to be in accordance with the standard, we present the guidelines of
      the GEHT (Groupe d'etude d'hemostase et thrombose) subcommittee "CEC et Biologie
      delocalisee" for the certification of ACT. These guidelines are based on the SFBC
      guidelines for the certification of POCT and on the analysis of the literature to
      ascertain the justification of clinical need and assess the analytical
      performance of main analyzers used in France, as well as on a survey conducted
      with French and Belgian biologists. 

PMID- 25847748
TI  - [Measurements of PSA and of vitamin D: a period of 3-months of use of special
      forms based on the guidelines of the Haute autorite de sante shows a clear
      improvement of prescription behaviors].
AB  - In France practice guidelines of the Haute Autorite de sante (HAS) are not
      implemented as often as they should. As a consequence resources are wasted that
      could be useful elsewhere. In Avril 2014 prescription-forms were introduced in
      our hospital for PSA and for vitamin-D. If those forms were not filled-in by the
      physicians, then PSA and vitamin-D were not measured any more by our laboratory.
      PSA was measured in only two circumstances: therapeutic follow-up of, or
      screening for, prostate cancer. Patients had to give their formal consent for
      being screened with PSA. Vitamin-D was measured in the only six circumstances
      recommended by the HAS. After a few months of use of these two forms we observe a
      sharp decrease in PSA, and even more so in vitamin D, measurements. Our
      prescription-forms' legitimacy is high because they are based on governmental
      guidelines. All the more since the values that are promoted in these guidelines
      clearly cover the four core principles of bioethics, that is beneficence, non
      malevolence, respect for the patient's autonomy (particularly for PSA) and
      equity. Our results need to be confirmed over a longer period of time, and to be
      analysed in more detail, particularly regarding the way consent forms are filled
      in by the patients. 

PMID- 25847749
TI  - Simple Resolution of Enantiomeric NMR Signals of alpha-Amino Acids by Using
      Samarium(III) Nitrate With L-Tartarate.
AB  - Readily available L-tartaric acid, which is a bidentate ligand with two chiral
      centers forming a seven-membered chelate ring, was applied to the chiral ligand
      for the chiral nuclear magnetic resonance (NMR) shift reagent of samarium(III)
      formed in situ. This simple method does not cause serious signal broadening in
      the high magnetic field. Enantiomeric (13)C and (1)H NMR signals and enantiotopic
      (1)H NMR signals of alpha-amino acids were successfully resolved at pH 8.0 and
      the 1:3 molar ratio of Sm(NO3)3:L-tartaric acid. It is elucidated that the
      enantiomeric signal resolution is attributed to the anisotropic magnetic
      environment for the enantiomers induced by the chiral L-tartarato samarium(III)
      complex rather than differences in stability of the diastereomeric substrate
      adducts. The present (13)C NMR signal resolution was also effective for the
      practical simultaneous analysis of plural kinds of DL-amino acids.

PMID- 25847750
TI  - Brain derived neurotrophic factor (BDNF) and autism spectrum disorders (ASD) in
      childhood.
AB  - BACKGROUND: Neurotrophic factors are essential regulators of neuronal maturation
      including synaptic synthesis. Among those, Brain derived neurotrophic factor
      (BDNF) has been in particular focus in the understanding of autism spectrum
      disorders (ASD). PURPOSE: The aim of our study was to investigate whether BNDF
      could be used as diagnostic/biological marker for ASD. For this purpose we
      examined the plasma levels of BDNF and the precursors pro- BDNF in patients with
      ASD and compared it with non-autistic controls; determined whether there was a
      correlation between the BDNF and proBDNF levels and clinical severity. We also
      investigated the coding region of BDNF identify for well-variations which could
      be associated to ASD. METHODS: The 65 ASD patients (51 boys) were enrolled from a
      recent completed epidemiological survey covering two counties (Oppland and
      Hedmark) in Norway. The mean age of the total number of children who participated
      in this study was 11,7 years. 30 non-autistic children were included as controls,
      14 boys and 16 girls. The mean age was 11.3 years. Exclusion criteria for control
      group were individuals suffering from either neurological, endocrine, or immune
      insuffiency. RESULTS AND CONCLUSIONS: Patients with ASD were characterized by
      moderately but significantly elevated plasma levels of BDNF compared to matched
      controls. No differences were observed in the proBDNF level between patients and
      controls. Within the ASD group, children with intellectual disability
      demonstrated increased BDNF, but not proBDNF levels, while the presence of ADHD
      had no impact on circulating proBDNF or BDNF. No further associations between
      plasma proBDNF or BDNF and other clinical demographics were observed.

PMID- 25847751
TI  - ABCB1 gene variants and antidepressant treatment outcome: A meta-analysis.
AB  - The efflux pump P-glycoprotein (P-gp), a gene product of the ABCB1 gene, plays a
      pivotal role in the transfer of various molecules across the blood-brain barrier.
      P-gp protects the brain by selectively extruding its substrates, including
      certain antidepressive drugs, thereby limiting their uptake into the brain. Uhr
      et al. [2008] first showed that ABCB1 variants predicted the remission to
      antidepressants with P-gp substrate properties in patients suffering from major
      depression (MD). Other studies investigating the influence of ABCB1 polymorphisms
      on antidepressant treatment response produced inconclusive results. In this meta
      analysis, we systematically summarized 16 pharmacogenetic studies focused on the
      association of ABCB1 variants and antidepressant treatment outcome in patients
      with MD (overall n = 2695). We investigated the association of treatment outcome
      and six ABCB1 single nucleotide polymorphisms (SNPs): rs2032583, rs2235015,
      rs2235040, rs1045642, rs2032582, rs1128503. We stratified for admission status,
      ethnicity, and prescription of concomitant medication. SNP rs2032583 showed a
      nominally significant association across all studies (P = 0.035, SNP was studied
      in a total of 2,037 patients) and a significant Bonferroni-corrected association
      among inpatients (P = 1.5 * 10(-05) , n = 485). Also SNP rs2235015 was
      significantly associated with antidepressant treatment outcome withstanding
      Bonferroni correction (P = 3.0 * 10(-04) ) among inpatients in a smaller
      subsample (n = 195). There were no significant associations of the other SNPs
      tested with antidepressant treatment outcome. Future pharmacogenetic association
      studies should focus on the role of the ABCB1 SNP rs2032583 in antidepressant
      outcome prediction.

PMID- 25847752
TI  - Enhancing agents for phytoremediation of soil contaminated by cyanophos.
AB  - Cyanophos is commonly used in Egypt to control various agricultural and
      horticultural pests. It is a strong contaminant in the crop culturing
      environments because it is highly persistent and accumulates in the soil. This
      contaminant can be removed by phytoremediation, which is the use of plants to
      clean-up pollutants. Here we tested several several strategies to improve the
      effectiveness of this technology, which involved various techniques to solubilize
      contaminants. The phytoremediation efficiency of Plantago major L. was improved
      more by liquid silicon dioxide (SiO2) than by other solubility-enhancing agents,
      resulting in the removal of significant amounts of cyanophos from contaminated
      soil. Liquid SiO2 increased the capacity of P. major L. to remove cyanophos from
      soil by 45.9% to 74.05%. In P. major L. with liquid SiO2, leaves extracted more
      cyanophos (32.99 ug/g) than roots (13.33 ug/g) over 3 days. The use of
      solubilization agents such as surfactants, hydroxypropyl-beta-cyclodextrin
      (HPbetaCD), natural humic acid acid (HA), and Tween 80 resulted in the removal of
      60 convergents of cyanophos from polluted soil. Although a batch equilibrium
      technique showed that use of HPbetaCD resulted in the efficient removal of
      cyanophos from soil, a greater amount of cyanophos was removed by P. major L.
      with SiO2. Moreover, a large amount of cyanophos was removed from soil by rice
      bran. This study indicates that SiO2 can improve the efficiency of
      phytoremediation of cyanophos.

PMID- 25847753
TI  - Occurrences of pharmaceuticals in drinking water sources of major river
      watersheds, China.
AB  - Pharmaceuticals in drinking water sources (DWSs) have raised significant concerns
      for their persistent input and potential human health risks. Currently, little is
      known about the occurrence of pharmaceuticals in DWSs in China. In this study, a
      survey for multi-class pharmaceuticals in DWSs of five major river watersheds in
      China was conducted from 2012 to 2013. Samples were collected from 25 sampling
      sites in rivers and reservoirs. 135 pharmaceuticals were analyzed using solid
      phase extraction and ultra-performance liquid chromatography tandem mass
      spectrometry. The results showed that a total of 70 pharmaceuticals were present
      in the samples, and the most frequently detected ones included sulfonamides,
      macrolides, antiepileptic drugs, anti-inflammatory drugs, and beta-blockers, etc.
      Amongst these, maximum concentrations of lincomycin, sulfamethoxazole,
      acetaminophen and paraxanthine were between 44 ng/L and 134 ng/L, and those of
      metoprolol, diphenhydramine, venlafaxine, nalidixic acid and androstenedione were
      less than 1 ng/L. Concentrations of the two that were most persistent, DEET and
      carbamazepine, were 0.8-10.2 ng/L and 0.01-3.5 ng/L, respectively. Higher
      concentrations of cotinine were observed in warm season than in cold season,
      while concentrations of lincomycin were the opposite. In a causality analysis,
      the occurrence of pharmaceuticals in DWSs depends mainly on the detection limits
      of the methods, their usage and the persistence in the aquatic environment.

PMID- 25847754
TI  - Brief Report: Vision in Children with Autism Spectrum Disorder: What Should
      Clinicians Expect?
AB  - Anomalous visual processing has been described in individuals with autism
      spectrum disorder (ASD) but relatively few studies have profiled visual acuity
      (VA) in this population. The present study describes presenting VA in children
      with ASD (n = 113) compared to typically developing controls (n = 206) and best
      corrected visual acuity (BCVA) in a sub-group of children with ASD (n = 29).
      There was no statistically significant difference in presenting VA between groups
      (z = -1.75, p = 0.08); ASD group median VA (interquartile range, IQR) -0.05
      logMAR (IQR: -0.125 to 0.025 logMAR) and typically developing control group 
      0.075 logMAR (IQR: -0.150 to -0.025 logMAR). Median BCVA was -0.175 logMAR (IQR: 
      0.200 to -0.125 logMAR) for the ASD sub-group. Clinicians should not anticipate
      reduced VA when assessing children with ASD.

PMID- 25847755
TI  - Examination of the Korean Modified Checklist of Autism in Toddlers: Item Response
      Theory.
AB  - The study examined the clinical utility and psychometric properties of the Korean
      Modified Checklist of Autism in Toddlers (K-M-CHAT)-2. A sample of 2300 parents
      of 16- to 36-month-old children was recruited across South Korea. A phone
      interview was utilized to follow up with participants who initially screened
      positive for autism spectrum disorder (ASD). Item response theory was applied to
      assess the psychometric properties of the K-M-CHAT-2. Parents' responses were
      substantially changed after the follow-up, and the final screen-positive rate was
      2.3 %. Results indicated that the psychometric properties of items 1, 3, 11, 18
      and 22 were not as strong as the other items. The K-M-CHAT-2 is a useful ASD
      screening test when implemented with a follow-up.

PMID- 25847756
TI  - Psychosocial Adjustment and Sibling Relationships in Siblings of Children with
      Autism Spectrum Disorder: Risk and Protective Factors.
AB  - This study compared sibling adjustment and relationships in siblings of children
      with Autism Spectrum Disorder (ASD-Sibs; n = 69) and siblings of children with
      typical development (TD-Sibs; n = 93). ASD-Sibs and TD-Sibs demonstrated similar
      emotional/behavioral adjustment. Older male ASD-Sibs were at increased risk for
      difficulties. Sibling relationships of ASD-Sibs involved less aggression, less
      involvement, and more avoidance than those of TD-Sibs. Partial support for a
      diathesis-stress conceptualization of sibling difficulties was found for ASD
      Sibs. For TD-Sibs, broader autism phenotype (BAP) was related to psychosocial
      difficulties regardless of family stressors. For ASD-Sibs, BAP was related to
      difficulties only when family stressors were present. This suggests that having a
      sibling with ASD may be a protective factor that attenuates the negative impact
      of sibling BAP.

PMID- 25847758
TI  - Catalytic asymmetric hydrogenation of quinoline carbocycles: unusual
      chemoselectivity in the hydrogenation of quinolines.
AB  - The reduction of quinolines selectively took place on their carbocyclic rings to
      give 5,6,7,8-tetrahydroquinolines, when the hydrogenation was conducted in the
      presence of a Ru(eta(3)-methallyl)2(cod)-PhTRAP catalyst. The chiral ruthenium
      catalyst converted 8-substituted quinolines into chiral 5,6,7,8
      tetrahydroquinolines with up to 91 : 9 er. 

PMID- 25847757
TI  - Are Autistic Traits in the General Population Related to Global and Regional
      Brain Differences?
AB  - There is accumulating evidence that autistic-related traits in the general
      population lie on a continuum, with autism spectrum disorders representing the
      extreme end of this distribution. Here, we tested the hypothesis of a possible
      relationship between autistic traits and brain morphometry in the general
      population. Participants completed the short autism-spectrum quotient
      questionnaire (AQ); T1-anatomical and DWI-scans were acquired. Associations
      between autistic traits and gray matter, and white matter microstructural
      integrity were performed on the exploration-group (N = 204; 105 males, M-age =
      22.85), and validated in the validation-group (N = 304; 155 males, M-age =
      22.82). No significant associations were found between AQ-scores and brain
      morphometry in the exploration-group, or after pooling the data. This questions
      the assumption that autistic traits and their morphological associations do lie
      on a continuum in the general population.

PMID- 25847759
TI  - Experiences with the flow-through radial forearm flap as a bridge in lower
      extremity reconstruction.
AB  - Various techniques have been proposed in order to overcome recipient vessel
      problems in microsurgery. In cases with no suitable recipient vessels close to
      the defect, the flow-through flap is a valuable and reliable alternative for
      accessing healthy recipient vessels in a single stage. We describe our
      experiences with combined flaps and discuss the advantages of the flow-through
      radial forearm flap as a bridge. Between 2003 and 2009, eight combined flaps were
      used to reconstruct soft-tissue defects of lower extremities. Seven patients had
      acute or subacute wound with exposed bone and vascular injury caused by trauma,
      one had a chronic nonhealing wound. The flow-through radial forearm flap was used
      as a bridge flap with combined a cover flap in all cases. Radial forearm flaps
      provided recipient vessel lengthening. In one patient, the distal ALT flap failed
      and replaced with latissimus dorsi flap. Other postoperative courses were
      uneventful and all of flaps survived. In one patient although the flaps were
      healthy, sepsis developed and the extremity was amputated. Recovery and
      ambulation were achieved in the remaining patients. Combined flaps with the flow
      through radial forearm flap are an appropriate technique for overcoming recipient
      vessel problems. Although the technique involves a more complicated procedure and
      increases the number of microvascular anastomoses, it is a valuable, safe and
      comfortable alternative in selected cases.

PMID- 25847760
TI  - Comparison of properties of new sources of partially purified inulin to those of
      commercially pure chicory inulin.
AB  - Newly developed inulin powders were prepared from roots of Asparagus falcatus
      (AF) and Taraxacum javanicum (TJ) plants grown in Sri Lanka. Inulin content,
      analyzed by enzymatic spectrophotometric as well as high-performance liquid
      chromatographic methods, showed that AF and TJ inulin powders contain 65.5% and
      45.4% (dry wt) inulin, respectively, compared with 72% dry wt in the commercially
      available chicory inulin. Treating the AF and TJ inulin powders using ion
      exchange techniques significantly (P < 0.05) reduced their contents of micro (Zn,
      Cu, Mn, Fe) and macro (Na, K, Ca, Mg) elements. Enzymatic hydrolysis of inulin
      into fructose and glucose by fructanase, and FT-IR analyses proved that the
      developed AF and TJ inulins have characteristic molecular composition similar to
      commercial inulin. TJ inulin contained significantly (P < 0.05) greater amounts
      of total phenolics (4.37 mg GAE/g), total flavonoids (2.79 mg QE/g), and
      antioxidant capacity (833.11 mM TE/g) than AF inulin, which contained 1.33 mg
      GAE/g of total phenolics, 0.43 mg QE/g of total flavonoids, and 406.26 mM TE/g
      antioxidant capacity. The current study suggests that the newly developed inulin
      from AF and TJ roots could be used as an alternative commercial source of inulin
      for the food industry.

PMID- 25847764
TI  - Acupuncture practice acts: a profession's growing pains.
AB  - State legislation that authorizes any healthcare profession is known as the
      Practice Act. In order for a profession to establish a recognizable national
      presence and be integrated into mainstream medicine, all the state Practice Acts
      must evidence consistency. The extent to which state Practice Acts fail to
      exhibit consistency can inhibit the ability of the profession to grow and become
      successful. We looked at the histories of other health professions, along with
      the 45 acupuncture Practice Acts in the USA, in order to understand the time worn
      paths that lead to integration in the mainstream and how the acupuncture
      profession might benefit. 

PMID- 25847765
TI  - Design, synthesis, biological evaluation and molecular docking studies of
      phenylpropanoid derivatives as potent anti-hepatitis B virus agents.
AB  - A series of phenylpropanoid derivatives were synthesized, and their anti
      hepatitis B virus (HBV) activity was evaluated in HepG 2.2.15 cells. Most of the
      synthesized derivatives showed effective anti-HBV activity. Of these compounds,
      compound 4c-1 showed the most potent anti-HBV activity, demonstrating potent
      inhibitory effect not only on the secretion of HBsAg (IC50 = 14.18 MUM, SI =
      17.85) and HBeAg (IC50 = 6.20 MUM, SI = 40.82) secretion but also HBV DNA
      replication (IC50 = 23.43 MUM, SI = 10.80). The structure-activity relationships
      (SARs) of phenylpropanoid derivatives had been discussed, which were useful for
      phenylpropanoid derivatives to be explored and developed as novel anti-HBV
      agents. Moreover, the docking study of all synthesized compounds inside the HLA-A
      protein (PDB ID: 3OX8) active site were carried out to explore the molecular
      interactions and a molecular target for activity of phenylpropanoid derivatives
      with the protein using a moe-docking technique. This study identified a new class
      of potent anti-HBV agents. 

PMID- 25847766
TI  - A new delivery system for auristatin in STxB-drug conjugate therapy.
AB  - A key challenge in anticancer therapy is to gain control over the biodistribution
      of cytotoxic drugs. The most promising strategy consists in conjugating drugs to
      tumor-targeting carriers, thereby combining high cytotoxic activity and specific
      delivery. To target Gb3-positive cancer cells, we exploit the non-toxic B-subunit
      of Shiga toxin (STxB). Here, we have conjugated STxB to highly potent auristatin
      derivatives (MMA). A former linker was optimized to ensure proper drug-release
      upon reaching reducing environments in target cells, followed by a self
      immolation step. Two conjugates were successfully obtained, and in vitro assays
      demonstrated the potential of this targeting system for the selective elimination
      of Gb3-positive tumors. 

PMID- 25847767
TI  - Synthesis and anticancer activity of N-substituted 2-arylquinazolinones bearing
      trans-stilbene scaffold.
AB  - A novel series of 2-arylquinazolinones 7a-o bearing trans-stilbene moiety were
      designed, synthesized, and evaluated against human breast cancer cell lines
      including human breast adenocarcinoma (MCF-7 and MDA-MB-231) and human ductal
      breast epithelial tumor (T-47D). Among the tested compounds, the sec-butyl
      derivative 7h showed the best profile of activity (IC50 < 5 MUM) against all cell
      lines, being 2-fold more potent than standard drug, etoposide. Our investigation
      revealed that the cytotoxic activity was significantly affected by N3-alkyl
      substituents. Furthermore, the morphological analysis by acridine orange/ethidium
      bromide double staining test and flow cytometry analysis indicated that the
      prototype compound 7h can induce apoptosis in MCF-7 and MDA-MB-231 cells. 

PMID- 25847768
TI  - Development of benzimidazole derivatives to inhibit HIV-1 replication through
      protecting APOBEC3G protein.
AB  - Human APOBEC3G (apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like
      3G, A3G) is a potent restriction factor against human immunodeficiency virus type
      1 (HIV-1) by inducing hypermutation of G to A in viral genome after its
      incorporation into virions. HIV-1 Vif (Virion Infectivity Factor) counteracts A3G
      by inducing ubiquitination and proteasomal degradation of A3G protein. Vif-A3G
      axis therefore is a promising therapeutic target of HIV-1. Here we report the
      screening, synthesis and SAR studies of benzimidazole derivatives as potent
      inhibitors against HIV-1 replication via protecting A3G protein. Based on the
      steep SAR of the benzimidazole scaffold, we identified compound 14 and 26 which
      provided the best potency, with IC50 values of 3.45 nM and 58.03 nM respectively
      in the anti-HIV-1 replication assay in H9 cells. Compound 14 and 26 also afforded
      protective effects on A3G protein level. Both compounds have been proved to be
      safe in acute toxicological studies. Taken together, we suggest that these two
      benzimidazole derivatives can be further developed as a new category of anti-HIV
      1 leads. 

PMID- 25847769
TI  - Novel imidazo[2,1-b]-1,3,4-thiadiazoles as promising antifungal agents against
      clinical isolate of Cryptococcus neoformans.
AB  - We herein report the synthesis and in vitro antimicrobial evaluation of twenty
      five novel hybrid derivatives of imidazo [2,1-b]-1,3,4-thiadiazole containing
      chalcones (5a-o) and Schiff bases (6a-j) against three fungal strains (Candida
      albicans, Cryptococcus neoformans and Aspergillus niger). Most of the tested
      compounds displayed substantial anti-fungal activity with MICs ranging between
      1.56 and 100 MUg/mL. Compounds 5a, 5b and 5n exhibited promising activity against
      C. neoformans at a MIC 1.56 MUg/mL. In addition, compound 5n also demonstrated
      significant antifungal activity against the clinical isolates of C. neoformans at
      MIC 3.125 MUg/mL. However, moderate activity was observed for these compounds
      against four bacterial strains (Staphylococcus aureus, Bacillus subtilis,
      Escherichia coli and Pseudomonas aeruginosa) and Mycobacterium tuberculosis
      (H37Rv). 

PMID- 25847770
TI  - Structure-activity relationship and properties optimization of a series of
      quinazoline-2,4-diones as inhibitors of the canonical Wnt pathway.
AB  - Wnt signaling pathway plays a critical role in numerous cellular processes,
      including tumor initiation, proliferation, invasion/infiltration, metastasis
      formation and resistance to chemotherapy. In a drug discovery project aimed at
      the identification of inhibitors of the canonical Wnt pathway, we selected a
      series of quinazoline 2,4-diones as starting point for the therapeutic treatment
      of glioblastoma multiforme. Despite of poor physico-chemical properties of hit
      compound 1, our medicinal chemistry effort allowed the discovery and
      characterization of lead compound 33 (SEN461), with improved ADME profile, good
      bioavailability and active in vitro and in vivo in glioblastoma, gastric and
      sarcoma tumors. 

PMID- 25847771
TI  - Towards small molecule inhibitors of mono-ADP-ribosyltransferases.
AB  - Protein ADP-ribosylation is a post-translational modification involved in DNA
      repair, protein degradation, transcription regulation, and epigenetic events.
      Intracellular ADP-ribosylation is catalyzed predominantly by ADP
      ribosyltransferases with diphtheria toxin homology (ARTDs). The most prominent
      member of the ARTD family, poly(ADP-ribose) polymerase-1 (ARTD1/PARP1) has been a
      target for cancer drug development for decades. Current PARP inhibitors are
      generally non-selective, and inhibit the mono-ADP-ribosyltransferases with low
      potency. Here we describe the synthesis of acylated amino benzamides and
      screening against the mono-ADP-ribosyltransferases ARTD7/PARP15, ARTD8/PARP14,
      ARTD10/PARP10, and the poly-ADP-ribosyltransferase ARTD1/PARP1. The most potent
      compound inhibits ARTD10 with sub-micromolar IC50. 

PMID- 25847772
TI  - Acupuncture treatment modulates the resting-state functional connectivity of
      brain regions in migraine patients without aura.
AB  - OBJECTIVE: To investigate the modulatory effect of acupuncture treatment on the
      resting-state functional connectivity of brain regions in migraine without aura
      (MWoA) patients. METHODS: Twelve MWoA patients were treated with standard
      acupuncture treatment for 4 weeks. All MWoA patients received resting-state
      functional magnetic resonance imaging (fMRI) scanning before and after
      acupuncture treatment. Another 12 normal subjects matched in age and gender were
      recruited to serve as healthy controls. The changes of restingstate functional
      connectivity in MWoA patients before and after the acupuncture treatment and
      those with the healthy controls were compared. RESULTS: Before acupuncture
      treatment, the MWoA patients had significantly decreased functional connectivity
      in certain brain regions within the frontal and temporal lobe when compared with
      the healthy controls. After acupuncture treatment, brain regions showing
      decreased functional connectivity revealed significant reduction in MWoA patients
      compared with before acupuncture treatment. CONCLUSIONS: Acupuncture treatment
      could increase the functional connectivity of brain regions in the intrinsic
      decreased brain networks in MWoA patients. The results provided further insights
      into the interpretation of neural mechanisms of acupuncture treatment for
      migraine.

PMID- 25847773
TI  - Extract of Zuojin Pill ([characters: see text]) induces apoptosis of SGC-7901
      cells via mitochondria-dependent pathway.
AB  - OBJECTIVE: To observe the effects of water extract of Zuojin Pill ([characters:
      see text], ZJP) on inhibiting the growth of human gastric cancer cell line SGC
      7901 and its potential mechanism. METHODS: Effects of ZJP on SGC-7901 cells
      growth were determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H
      tetrazolium bromide (MTT) assay, cell apoptosis and cell cycle were determined by
      flow cytometry, and apoptosis induction was detected by means of DNA gel
      electrophoresis. The cellular mechanism of drug-induced cell death was unraveled
      by assaying oxidative injury level of SGC-7901 cell, mitochondrial membrane
      potentials, expression of apoptosis-related genes, such as B cell
      lymphoma/lewkmia-2 (Bcl-2), Bcl-2 associated X protein (Bax) and cleaved caspase
      3 and caspase-9. RESULTS: ZJP exerted evident inhibitory effect on SGC-7901 cells
      by activating production of reactive oxygen species and elevating Bax/Bcl-2 ratio
      in SGC-7901 cells, leading to attenuation of mitochondrial membrane potential and
      DNA fragmentation. CONCLUSIONS: ZJP inhibits the cancer cell growth via
      activating mitochondria-dependent apoptosis pathway. ZJP can potentially serve as
      an antitumor agent.

PMID- 25847774
TI  - Electroacupuncture attenuates spinal nerve ligation-induced microglial activation
      mediated by p38 mitogen-activated protein kinase.
AB  - OBJECTIVE: To investigate whether analgesic effect of electroacupuncture (EA) is
      affected by p38 mitogen-activated protein kinase (p38 MAPK) on microglia.
      METHODS: There were two experiments. The experiment 1: 40 male Sprague-Dawley
      (SD) rats were randomly divided into the normal, surgery, EA and sham EA groups,
      and the L5 spinal nerve ligation (SNL) on the right side was used to establish
      neuropathic pain model. EA was applied to bilateral Zusanli (ST36) and Kunlun
      (BL60) at 24, 48 and 72 h after SNL for 30 min, once per day. The paw withdrawal
      thresholds (PWTs) were measured before surgery (as base) and at 24, 25, 49 and 73
      h after surgery. Phospho-p38 MAPK (p-p38 MAPK), oxycocin-42 (OX-42, marker of
      microglia), and glial fibrillary acidic protein (GFAP, marker of astrocyte) in
      bilateral spinal cord dorsal horn (SCDH) were detected by immunofluorescence,
      respectively. The experiment 2: 40 male SD rats were cannulated for SNL-induced
      neuropathic pain, and then were randomly divided into the dimethyl sulfoxide
      (DMSO), EA plus DMSO, 4-(4-fluorophenyl)-2-(4-methylsulfonylpheny)-5-(4-pyridyl)
      1H-imidazole (SB203580) and EA plus SB203580 groups. SB203580 (30 nmol/L) was
      administered 5 min prior to EA treatment. The PWTs and OX-42 in bilateral SCDH
      were measured as mentioned above. RESULTS: SNL-induced neuropathic pain reduced
      PWTs and increased the expression of p-p38 MAPK and OX-42 in bilateral lumbar
      SCDH of rats (P<0.01). Spinal p-p38 MAPK was only co-localized with OX-42 in our
      study. EA treatment significantly alleviated SNL-mediated mechanical
      hyperalgesia, and suppressed the expression of p-p38 MAPK and OX-42 in lumbar
      SCDH (P<0.05 or P<0.01). Intrathecal injection of low dose SB203580 had no
      influence on PWTs (P>0.05), but significantly inhibited the expression of OX-42
      positive cells in bilateral SCDH (P<0.01 or P<0.05). EA plus SB203580
      synergistically increased PWTs, and reduced the expression of bilateral spinal OX
      42 (P<0.01 or P<0.05). CONCLUSIONS: The central mechanism of EA-induced anti
      hyperalgesia may be partially associated with the reduced expression of p-p38
      MAPK, and subsequently reducing the activation of OX-42 in neuropathic pain.
      Therefore, EA may be a new complementary and alternative therapy for neuropathic
      pain.

PMID- 25847775
TI  - Effect of Huanshuai Recipe Oral Liquid ([characters: see text]) on renal
      dysfunction progression in patients with atherosclerotic renal artery stenosis.
AB  - OBJECTIVE: To investigate the effect of Huanshuai Recipe Oral Liquid
      ([characters: see text], HSR) on retarding the progression of renal dysfunction
      in patients with atherosclerotic renal artery stenosis (ARAS). METHODS: A total
      of 52 ARAS patients with the Chinese medicine (CM) syndrome of qi deficiency and
      blood stasis, phlegm and dampness retention were recruited and randomly assigned
      into the treatment group (36 cases) and the control group (16 cases). Both groups
      received a basic treatment (high-quality low-protein diet, blood pressure
      control, lipid-lowering, correcting the acidosis, etc.). In addition, the
      treatment group received 20 mL HSR and the control group received placebo, 3
      times a day for 6 months. Renal function (serum creatinine, blood urea nitrogen
      and uric acid) and blood lipids (cholesterol, triglycerides and low density
      lipoprotein) were examined monthly. The estimated glomerular filtration rate
      (eGFR) and CM syndrome score were compared between groups. RESULTS: After
      treatment, compared with the control group, the serum creatinine level, uric acid
      level and CM syndrome score of the treatment group were significantly decreased
      (P<0.05 or P<0.01), and the eGFR in the treatment group were significantly
      increased (P<0.05). CONCLUSION: HSR can effectively improve the renal function
      and clinical symptoms of ARAS patients.

PMID- 25847776
TI  - Wendan decoction (???) for treatment of schizophrenia: a systematic review of
      randomized controlled trials.
AB  - OBJECTIVE: To assess the beneficial and adverse effects of Wendan Decoction (???,
      WDD) for the treatment of schizophrenia. METHODS: Five electronic databases were
      searched until May 2014, including the Chinese National Knowledge Infrastructure,
      the Chinese Biomedical Literature Database, the Chinese Scientist Journal
      Database, PubMed, and the Cochrane Central Register of Controlled Trials in the
      Cochrane Library. The randomized controlled trials (RCTs) testing WDD against
      placebo, antipsychotic drugs, or WDD combined with antipsychotic drugs against
      antipsychotic drugs alone were included. Study selection, data extraction,
      quality assessment, and data analyses were conducted according to the Cochrane
      standards. RESULTS: Thirteen RCTs (involving 1,174 patients) were included and
      the methodological quality was evaluated as generally low. The pooled results
      showed that WDD combined with antipsychotic drugs were more effective in clinical
      comprehensive effect, Positive and Negative Syndrome Scale (PANSS) scores and
      Brief Psychiatric Rating Scale scores compared with antipsychotic drugs alone.
      However, WDD had less effectiveness compared with antipsychotics in clinical
      comprehensive effect; and WDD was not different from antipsychotic drugs for
      PANSS scores. The side effects were significantly reduced in the intervention
      group compared with the control group. CONCLUSIONS: WDD appears to be effective
      on improving symptoms in patients with schizophrenia. However, due to poor
      methodological quality in the majority of the included trials, the potential
      benefit from WDD needs to be confirmed in rigorous trials and the design and
      reporting of trials should follow the international standards.

PMID- 25847777
TI  - Protective effects of Radix Astragali injection on multiple organs of rats with
      obstructive jaundice.
AB  - OBJECTIVE: To investigate the protective effects and mechanisms of Radix
      Astragali Injection on multiple organs of rats with obstructive jaundice (OJ).
      METHODS: A total of 180 rats were randomly divided into the sham-operated, model
      control and treated groups (60 in each group). On 7, 14, 21 and 28 days after
      operation, the serum contents of alanine aminotransferase (ALT), aspartate
      aminotransferase (AST), r-glutamyl transpeptidase (r-GT), total bilirubin (TBil),
      direct bilirubin (DBil), blood urine nitrogen (BUN), and creatinine (CREA) were
      determined. And the pathological changes of livers, kidneys and lungs, and
      protein expressions of toll-like receptor-4 (TLR-4) of livers, intercellular
      adhesion molecule-1 (ICAM-1) of lungs, Bax and nuclear factor-kappa B (NF
      kappaB), as well as apoptotic indexes of multiple organs were observed,
      respectively. RESULTS: The pathological severity scores of multiple organs
      (including livers on 7, 14, 21 and 28 days, kidneys on 14 and 28 days, and lungs
      on 14 days), serum contents of ALT (14 and 21 days), AST (14 days), TBil (7, 14,
      21 and 28 days), DBil (14 and 21 days), BUN (28 days), protein expressions of TLR
      4 (in livers, 28 days), Bax (in livers and kidneys, 21 days), and apoptotic
      indexes in livers (7 and 21 days) in the treated group were significantly lower
      than those in the model control group (P<0.05 or P<0.01). CONCLUSION: Radix
      Astragali Injection exerts protective effects on multiple organs of OJ rats by
      improving the pathological changes of lung, liver and kidney, decreasing the
      serum index of hepatic and renal function as well as inhibiting the protein
      expression of TLR-4 and Bax in the livers and Bax in the kidneys.

PMID- 25847778
TI  - Comparison of electroacupuncture and moxibustion on brain-gut function in
      patients with diarrhea-predominant irritable bowel syndrome: A randomized
      controlled trial.
AB  - OBJECTIVE: To compare the effects of electroacupuncture (EA) and moxibustion
      therapies on patients with diarrhea-predominant irritable bowel syndrome (D-IBS).
      METHODS: A total of 60 D-IBS patients were randomly allocated to the EA group (30
      cases) and moxibustion group (30 cases). Before and after treatment, the
      gastrointestinal symptoms and psychological symptoms were scored by Visual
      Analogue Scale, Bristol Stool Form Scale, Hamilton Anxiety Rating Scale (HAMA),
      and Hamilton Depression Rating Scale (HAMD); the expressions of 5
      hydroxytryptamine (5-HT), 5-HT3 receptor (5-HT3R), and 5-HT4 receptor (5-HT4R) in
      the sigmoid mucosal tissue were measured by immunohistochemical staining.
      Additionally, the effects on the functional brain areas of the anterior cingulate
      cortex (ACC), insular cortex (IC) and prefrontal cortex (PFC) were observed by
      functional magnetic resonance imaging. RESULTS: Compared with before treatment,
      both EA and moxibustion groups reported significant improvements in abdominal
      pain and abdominal bloating after treatment (P<0.01 or P<0.05). The moxibustion
      group reported greater improvements in defecation emergency, defecation
      frequency, and stool feature than the EA group (P<0.01). Both HAMA and HAMD
      scores were significantly decreased in the moxibustion group than in the EA group
      (P<0.01). Both groups demonstrated significantly reduced expressions of 5-HT, 5
      HT3R and 5-HT4R in the colonic mucosa after treatment (P<0.01), with a greater
      reduction of 5-HT in the moxibustion group (P<0.05). Finally, decreased activated
      voxel values were observed in the left IC, right IC and PFC brain regions of
      patients in the moxibustion group under stimulation with 150 mL colorectal
      distension after treatment (P<0.05 or P<0.01), while in the EA group only PFC
      area demonstrated a reduction (P<0.05). CONCLUSION: Moxibustion can significantly
      improve the symptoms of D-IBS, suggesting that moxibustion may be a more
      effective therapy than EA for D-IBS patients.

PMID- 25847779
TI  - Xuezhikang () reduced renal cell apoptosis in streptozocin-induced diabetic rats
      through regulation of Bcl-2 family.
AB  - OBJECTIVE: To investigate the effect of Xuezhikang (, XZK) on renal cell
      apoptosis in diabetic rats and the possible mechanism. METHODS: Sixty-six rats
      were randomly divided into 3 groups: the normal, model and XZK groups. In each
      group, the rats were further randomly divided into 3-month and 6-month subgroups,
      respectively. Diabetes of rats was induced by a single intraperitoneal injection
      of 1% streptozocin at 60 mg/kg body weight. Rats in the XZK group received
      gastric perfusion of XZK (1200 mg/kg body weight) everyday for 3 or 6 months,
      while rats in the normal and model groups received equal volume of saline. Twenty
      four hours' urine was collected for urinary albumin excretion (UAE) measurement.
      Periodic acid-Schiff (PAS) and Masson's trichrome staining were used for
      saccharides and collagen detection. Cell apoptosis of renal cortex was
      investigated by TdT-mediated dUTP nick end labeling (TUNEL) staining. Bax and Bcl
      2 expressions were detected by immunohistochemistry and Western blot,
      respectively. Cytochrome C (Cyt C) and caspase-9 concentration were detected by
      Western blot. RESULTS: Compared with the model group, XZK treatment could
      significantly decrease the kidney hypertrophy index, 24 h UAE, renal cell
      apoptosis, cytoplasmic Cyt C level and active caspase-9 level, as well as
      suppress the increment of Bax and up-regulate the expression of Bcl-2, leading to
      the suppression of Bax/Bcl-2 ratio at 3 and 6 months (P<0.05 or P<0.01).
      Moreover, XZK treatment could alleviate the deposition of PAS-stained saccharides
      and Masson's trichromestained collagen to different extent. CONCLUSIONS: Renal
      cell apoptosis was observed in diabetic kidney, in which mitochondrial apoptotic
      pathway might be involved. XZK treatment could attenuate pathological changes in
      diabetic kidney and reduce renal cell apoptosis, probably via the suppression of
      Bax/Bcl-2 ratio, which lead to inhibition of Cyt C release and following caspase
      9 activation.

PMID- 25847780
TI  - Phytopharmacological Profile of Jasminum grandiflorum Linn. (Oleaceae).
AB  - Plants are the real basis towards animal life and are also central to people's
      livelihood. The contributions of the plants in performing varied religious
      celebrations and in other multiple beneficiaries like medicine, human happiness
      as well as in treating deadly diseases can never be neglected. In treating
      diseases, the plants and their constituents are better choice than any other
      synthetic chemical. The nature has been kind enough to provide the human beings
      with various types of medicinal plants and in the real sense these form the
      storehouse of curing almost all the ailments. Consequently, most of the drugs
      which are being used in preparing formulations have their origin and roots in the
      plants which form the chief natural source of medicines. Even in modern era, the
      plant-derived drugs are being extensively used, either in their original or semi
      synthetic form. It is because their natural phytoconstituents are highly
      innocuous posing relatively fewer or no side effects. Based upon their
      observations, analysis and experience, our ancestors used many plants for
      medicinal purposes and thus their efforts need to be supported by scientific
      evidence. Jasminum grandiflorum Linn. is one of such important plants. It has
      been extensively used by the tribes all over India to treat different diseases
      which mainly include body pains, toothache, stomach ache, ulcers, and sexual
      impotency. Chemistry of the plant revealed the presence of mainly secoiridoids,
      terpenoids, flavonoids and tannins. Not much scientific support was given to the
      folklore claims for this plant but some of its traditional uses were investigated
      like spasmolytic, wound healing, antimicrobial, angiotensin converting enzyme
      inhibitor, antiulcer and antioxidant activities. This article is the review of
      research works done on the plant Jasminum grandiflorum Linn. to date. As a part
      of it the local names, morphology, traditional claims, chemistry and
      pharmacological activities have been discussed. 

PMID- 25847781
TI  - Palladium-catalyzed hydrocarboxylation of alkynes with formic acid.
AB  - A palladium-catalyzed hydrocarboxylation of alkynes with formic acid has been
      developed. The method provides acrylic acid and derivatives in good yields with
      high regioselectivity without the need to handle toxic CO gas. 

PMID- 25847783
TI  - A SEM, EDS and vibrational spectroscopic study of the tellurite mineral:
      Sonoraite Fe(3+)Te(4+)O3(OH).H2O.
AB  - We have undertaken a study of the tellurite mineral sonorite using electron
      microscopy with EDX combined with vibrational spectroscopy. Chemical analysis
      shows a homogeneous composition, with predominance of Te, Fe, Ce and In with
      minor amounts of S. Raman spectroscopy has been used to study the mineral
      sonoraite an examples of group A(XO3), with hydroxyl and water units in the
      mineral structure. The free tellurite ion has C3v symmetry and four modes, 2A1
      and 2E. An intense Raman band at 734 cm(-1) is assigned to the nu1 (TeO3)(2-)
      symmetric stretching mode. A band at 636 cm(-1) is assigned to the nu3 (TeO3)(2-)
      antisymmetric stretching mode. Bands at 350 and 373 cm(-1) and the two bands at
      425 and 438 cm(-1) are assigned to the (TeOv)(2-)nu2 (A1) bending mode and
      (TeO3)(2-)nu4 (E) bending modes. The sharp band at 3283 cm(-1) assigned to the OH
      stretching vibration of the OH units is superimposed upon a broader spectral
      profile with Raman bands at 3215, 3302, 3349 and 3415 cm(-1) are attributed to
      water stretching bands. The techniques of Raman and infrared spectroscopy are
      excellent for the study of tellurite minerals.

PMID- 25847782
TI  - Inhibition of farnesyl pyrophosphate synthase attenuates angiotensin II-induced
      fibrotic responses in vascular smooth muscle cells.
AB  - Through the regulation of the RhoA/Rho kinase (ROCK) pathway, angiotensin II (Ang
      II)-induced fibrotic responses contribute to vascular remodeling. Farnesyl
      pyrophosphate synthase (FPPS) plays an important role in cardiovascular
      remodeling through the modulation of the above-mentioned pathway. However, the
      role of FPPS in Ang II-induced fibrotic responses and the related molecular
      mechanisms have not yet been elucidated. In the present study, vascular smooth
      muscle cells (VSMCs) from Sprague-Dawley (SD) rats were stimulated with Ang II.
      Cell proliferation was measusred usin the cell counting kit-8 (CCK-8). The levels
      of connective tissue growth factor (CTGF), FPPS, and those of phosphorylated and
      total extracellular signal-regulated kinase (ERK)1/2, p38 and c-Jun N-terminal
      kinase (JNK) were determined by western blot analysis. RhoA activity was
      determined using a pull-down assay. The results revealed that stimulation with
      Ang II enhanced cell proliferation, and increased the protein expression levels
      of FPPS and CTGF in the VSMCs. The inhibition of FPPS with ibandronate sodium
      attenuated the Ang II-induced increase in cell proliferation, CTGF expresison and
      RhoA activity; these effects were partially reversed by treatment with
      geranylgeraniol and were mimicked by GGTI-286. Furthermore, both SB203580 (a
      specific inhibitor of p38) and SP600125 (JNK1, JNK2 and JNK3 inhibitor)
      diminished the Ang II-induced production of CTGF; however, the inhibition of FPPS
      reduced the Ang II-induced activation of p38 mitogen-activated protein kinase
      (MAPK) and JNK. In conclusion, our data indicate that FPPS may play an important
      role in Ang II-induced fibrotic responses in VSMCs, and the underlying mechanisms
      at least partly involve the modulation of RhoA activity, and the p38 and JNK
      pathways.

PMID- 25847784
TI  - A SEM, EDS and vibrational spectroscopic study of the clay mineral fraipontite.
AB  - The mineral fraipontite has been studied by using a combination of scanning
      electron microscopy with energy dispersive analysis and vibrational spectroscopy
      (infrared and Raman). Fraipontite is a member of the 1:1 clay minerals of the
      kaolinite-serpentine group. The mineral contains Zn and Cu and is of formula
      (Cu,Zn,Al)3(Si,Al)2O5(OH)4. Qualitative chemical analysis of fraipontite shows an
      aluminium silicate mineral with amounts of Cu and Zn. This kaolinite type mineral
      has been characterised by Raman and infrared spectroscopy; in this way aspects
      about the molecular structure of fraipontite clay are elucidated.

PMID- 25847785
TI  - Vibrational spectra, NLO analysis, and HOMO-LUMO studies of 2-chloro-6
      fluorobenzoic acid and 3,4-dichlorobenzoic acid by density functional method.
AB  - The FTIR and FT-Raman spectra of 2-chloro-6-fluorobenzoic acid and 3,4
      dichlorobenzoic acid have been recorded in the region 4000-400 cm(-1) and 3500-50
      cm(-1), respectively. Utilizing the observed FTIR and FT-Raman data, a complete
      vibrational assignment and analysis of fundamental modes of the compounds were
      carried out. The optimized molecular geometries, vibrational frequencies,
      thermodynamic properties and atomic charge of the compounds were calculated by
      using density functional theory (B3LYP) method with 6-311+G and 6-311++G basis
      sets. The difference between the observed and scaled wave number values of most
      of fundamentals is very small. Unambiguous vibration assignment of all the
      fundamentals is made up the total energy distribution (TED). The calculated HOMO
      and LUMO energies show that charge transfer occurs within the molecules. Besides,
      molecular electro static potential (MESP), Mulliken's charge analysis, first
      order hyper polarizability and several thermodynamic properties were performed by
      the DFT method.

PMID- 25847786
TI  - Complementary analysis of tissue homogenates composition obtained by Vis and NIR
      laser excitations and Raman spectroscopy.
AB  - Raman spectroscopy and four excitation lines in the visible (Vis: 488, 532, 633
      nm) and near infrared (NIR: 785 nm) were used for biochemical analysis of rat
      tissue homogenates, i.e. myocardium, brain, liver, lung, intestine, and kidney.
      The Vis Raman spectra are very similar for some organs (brain/intestines and
      kidney/liver) and dominated by heme signals when tissues of lung and myocardium
      were investigated (especially with 532 nm excitation). On the other hand, the NIR
      Raman spectra are specific for each tissue and more informative than the
      corresponding ones collected with the Vis excitations. The spectra analyzed
      without any special pre-processing clearly illustrate different chemical
      composition of each tissue and give information about main components e.g. lipids
      or proteins, but also about the content of some specific compounds such as amino
      acid residues, nucleotides and nucleobases. However, in order to obtain the whole
      spectral information about tissues complex composition the spectra of Vis and NIR
      excitations should be collected and analyzed together. A good agreement of data
      gathered from Raman spectra of the homogenates and those obtained previously from
      Raman imaging of the tissue cross-sections indicates that the presented here
      approach can be a method of choice for an investigation of biochemical variation
      in animal tissues. Moreover, the Raman spectral profile of tissue homogenates is
      specific enough to be used for an investigation of potential pathological changes
      the organism undergoes, in particular when supported by the complementary FTIR
      spectroscopy.

PMID- 25847787
TI  - Novel spectrophotometric method for selective determination of compounds in
      ternary mixtures (dual wavelength in ratio spectra).
AB  - A simple selective spectrophotometric method for determination of compounds in
      ternary mixture was developed by combining the resolution power of two well-known
      methods that are commonly used for binary mixtures; namely ratio difference
      method and dual wavelength. The new method (dual wavelength in ratio spectra) was
      successfully applied for the determination of a ternary mixture of betamethasone
      dipropionate (BM), clotrimazole (CT) and benzyl alcohol (BA) in pure powder form
      and in their pharmaceutical preparation. The difference in amplitudes (DeltaP) in
      the ratio spectra at 252.0 and 258.0 nm (DeltaP(252.0-258.0 nm)) corresponds to
      BM, while DeltaP(266.8-255.4 nm) and DeltaP(254.2-243.5 nm) corresponds to CT and
      BA, respectively. The method was validated as per the USP 2005 guidelines. The
      developed method can be used in quality control laboratories for routine analysis
      of compounds in ternary mixtures.

PMID- 25847788
TI  - An abiotic receptor and its Cu(II) complex as selective 'turn-off' chemosensor
      for bisulfate ion.
AB  - The ligand 2,6-bis[(N-phenyl)amido]-4-methylphenol (receptor 1) and its
      copper(II) complex (receptor 2) having amide moiety have been designed and
      synthesized for selective sensing of anions. The anion recognition behavior of
      the receptor 1 and its copper complex (receptor 2) has been studied in
      acetonitrile. Quenching of fluorescence was observed for both receptors in
      presence of HSO4(-) anion whereas other physiologically and environmentally
      important anions such as F(-), Cl(-), Br(-), I(-), CN(-), OAc(-), HCO3(-), H2PO4(
      ), NO3(-), NO2(-) and SO4(2-) show fluorescence enhancement behavior. The sensing
      protocol has been studied both spectrophotometrically as well as
      spectrofluorometrically. Fluorescence quenching is suggested to proceed via both
      dynamic and static processes.

PMID- 25847789
TI  - Self-assembled supramolecular structure of 1-methyl piperazinium 4-nitrophenolate
      4-nitrophenol monohydrate single crystal: Synthesis, growth, thermal and photo
      physical properties.
AB  - A new photoactive organic crystal, 1-methyl piperazinium 4-nitrophenolate-4
      nitrophenol monohydrate (MP4NPM) has been synthesised at 35  degrees C. Good
      quality single crystals of MP4NPM have successfully been grown by slow
      evaporation solution growth technique. Single crystal X-ray diffraction analysis
      shows that MP4NPM belongs to monoclinic crystal system with space group P21/n.
      The molecular structure was further confirmed by modern spectroscopic techniques
      like FT-NMR (both 1D and 2D), FT-IR, UV-Vis-NIR and fluorescence. The UV-Vis-NIR
      spectrum was performed to understand the range of optical transparency and the
      results showed its suitability for nonlinear optical applications. Fluorescence
      emission revealed that MP4NPM can serve as a photo active material. Thermal
      properties of MP4NPM were investigated using simultaneous TG-DSC analysis.
      Frequency and temperature dependent dielectric properties were studied in the
      frequency range 500 Hz-5 MHz and 40-50  degrees C, respectively. Vicker's
      microhardness measurements revealed that MP4NPM belongs to the category of soft
      material. Kurtz and Perry powder technique shows that MP4NPM has SHG efficiency
      0.89 times that of potassium dihydrogen phosphate (KDP).

PMID- 25847790
TI  - Enhanced ultraviolet fluorescence in surface modified ZnO nanostructures: Effect
      of PANI.
AB  - ZnO:polyaniline nanocomposite (ZnO:PANI) films were prepared and their steady
      state fluorescence and time resolved photoluminescence properties were discussed.
      X-ray diffraction and infrared spectroscopy analyses confirmed the interaction
      and formation of ZnO:PANI composite films. Optical absorption spectrum of pure
      PANI showed two bands at 325 and 625 nm which were ascribed to pi->pi(*)
      transition in the benzoid and exciton formation in the quinoid rings,
      respectively. Pure ZnO nanoparticles exhibited a band at 369 nm was due to their
      exciton absorption and the composite films showed a broad band in the visible
      region and small intensity band at the UV region. Fluorescence spectra showed
      that the ultra violet emission of ZnO was enhanced about tenfold due to the
      electron transfer from PANI to ZnO nanoparticles and the suppression of visible
      emission was attributed to the surface passivation effect. The transfer of
      electron from PANI to ZnO and its decay dynamics were experimentally analyzed
      through time resolved fluorescence measurements.

PMID- 25847791
TI  - A surface-enhanced Raman study of N-methylquinolinium tricyanoquinodimethanide
      adsorbed on Ag nanospheres: Determination of molecular orientation and order.
AB  - Quinolinium tricyanoquinodimethanides are among the most promising molecules for
      electronic applications. Disorder can be detrimental to the desired electronic
      properties of a monolayer, and as such, a reliable method to characterize a
      monolayer without destroying or creating defects is paramount to determining
      potential applications. Here, the normal and surface-enhanced Raman scattering
      spectra of N-methylquinolinium tricyanoquinodimethanide (CH3Q-3CNQ) on silver
      coated nanosurfaces have been obtained and analyzed. Theoretical treatment of
      CH3Q-3CNQ was performed. Optimization and frequency search was conducted using
      the B3LYP functional with the 6-31G(d) basis set. A complete list of frequencies
      and assignments for the molecules are presented. The spectroscopic evidence
      points to the fact that a monolayer of CH3Q-3CNQ can be formed through the self
      assembly process, and the SERS data indicate that the monolayer attaches to the
      silver surface through the nitrile groups.

PMID- 25847792
TI  - Quantitative determination of isoquinoline alkaloids and chlorogenic acid in
      Berberis species using ultra high performance liquid chromatography with hybrid
      triple quadrupole linear ion trap mass spectrometry.
AB  - Berberis species are well known and used extensively as medicinal plants in
      traditional medicine. They have many medicinal values attributable to the
      presence of alkaloids having different pharmacological activities. In this study,
      a method was developed and validated as per international conference on
      harmonization guidelines using ultra high performance liquid chromatography with
      hybrid triple quadrupole-linear ion trap mass spectrometry operated in the
      multiple reaction monitoring mode for nine bioactive compounds, including
      protoberberine alkaloids, aporphine alkaloids and chlorogenic acid. This method
      was applied in different plant parts of eight Berberis species to determine
      variations in content of nine bioactive compounds. The separation was achieved on
      an ACQUITY UPLC CSHTM C18 column using a gradient mobile phase at flow rate 0.3
      mL/min. Calibration curves for all the nine analytes provided optimum linear
      detector response (with R(2) >=0.9989) over the concentration range of 0.5-1000
      ng/mL. The precision and accuracy were within RSDs <=2.4 and <=2.3%,
      respectively. The results indicated significant variation in the total contents
      of the nine compounds in Berberis species. 

PMID- 25847794
TI  - From isolated 1H-pyrazole cryptand anion receptors to hybrid inorganic-organic 1D
      helical polymeric anion receptors.
AB  - We report a novel 1-D helical coordination polymer formed by protonated polyamine
      1H-pyrazole cryptands interconnected by Cu(2+) metal ions that are able to
      encapsulate anionic species behaving as a multianion receptor. Switching from a
      monomeric receptor to a polymeric receptor is activated by metal ions and pH. 

PMID- 25847793
TI  - Intralesional tuberculin (PPD) versus measles, mumps, rubella (MMR) vaccine in
      treatment of multiple warts: a comparative clinical and immunological study.
AB  - Intralesional purified protein derivative (PPD) or mumps, measles, rubella (MMR)
      were not previously compared regarding their efficacy or mechanism of action in
      treatment of warts. We aimed to compare their efficacy in treatment of multiple
      warts and investigate their effect on serum interleukin (IL)-4 and IL-12. Thirty
      patients with multiple warts were included (10 treated with PPD, 10 with MMR, and
      10 with normal saline (control)). Injection was done every 3 weeks until
      clearance or maximum of three treatments. Clinical response of target and distant
      warts was evaluated. Serum ILs-4 and -12 were assessed before and after
      treatment. A significantly higher rate of complete response was found in target
      and distant warts with PPD (60% each) and MMR (80%, 40%, respectively) compared
      with controls (0%), with no significant difference between both treatments. After
      treatment, the control group showed the lowest serum IL-12 and IL-4 levels
      compared with the MMR- and PPD-treated groups with statistically significant
      difference in between. MMR resulted in a significantly higher serum IL-12 than
      PPD. With PPD, IL-4 was increased with statistically significant change compared
      with pretreat-ment level. Intralesional PPD and MMR show comparable efficacy and
      safety in treatment of multiple warts. Serum ILs-4 and-12 increase following
      antigen injection. 

PMID- 25847795
TI  - Biomass and lipid production of a local isolate Chlorella sorokiniana under
      mixotrophic growth conditions.
AB  - A local Chlorella sp. isolate with 97% rbcL sequence identity to Chlorella
      sorokiniana was evaluated in terms of its biomass and lipid production under
      mixotrophic growth conditions. Glucose-supplemented cultures exhibited increasing
      growth rate and biomass yield with increasing glucose concentration. Highest
      growth rate and biomass yield of 1.602 day(-1) and 687.5 mg L(-1), respectively,
      were achieved under 2 g L(-1) glucose. Nitrogen starvation up to 75% in the 1.0 g
      L(-1) glucose-supplemented culture was done to induce lipid accumulation and did
      not significantly affect the growth. Lipid content ranges from 20% to 27% dry
      weight. Nile Red staining showed more prominent neutral lipid bodies in starved
      mixotrophic cultures. C. sorokiniana exhibited enhanced biomass production under
      mixotrophy and more prominent neutral lipid accumulation under nitrogen
      starvation with no significant decrease in growth; hence, this isolate could be
      further studied to establish its potential for biodiesel production.

PMID- 25847796
TI  - Learning to care at the end.

PMID- 25847797
TI  - Cow's Milk Contamination of Human Milk Purchased via the Internet.
AB  - BACKGROUND: The US Food and Drug Administration recommends against feeding
      infants human milk from unscreened donors, but sharing milk via the Internet is
      growing in popularity. Recipient infants risk the possibility of consuming
      contaminated or adulterated milk. Our objective was to test milk advertised for
      sale online as human milk to verify its human origin and to rule out
      contamination with cow's milk. METHODS: We anonymously purchased 102 samples
      advertised as human milk online. DNA was extracted from 200 MUL of each sample.
      The presence of human or bovine mitochondrial DNA was assessed with a species
      specific real-time polymerase chain reaction assay targeting the nicotinamide
      adenine dinucleotide (NADH) dehydrogenase subunit 5 gene. Four laboratory-created
      mixtures representing various dilutions of human milk with fluid cow's milk or
      reconstituted infant formula were compared with the Internet samples to
      semiquantitate the extent of contamination with cow's milk. RESULTS: All Internet
      samples amplified human DNA. After 2 rounds of testing, 11 samples also contained
      bovine DNA. Ten of these samples had a level of bovine DNA consistent with human
      milk mixed with at least 10% fluid cow's milk. CONCLUSIONS: Ten Internet samples
      had bovine DNA concentrations high enough to rule out minor contamination,
      suggesting a cow's milk product was added. Cow's milk can be problematic for
      infants with allergy or intolerance. Because buyers cannot verify the composition
      of milk they purchase, all should be aware that it might be adulterated with
      cow's milk. Pediatricians should be aware of the online market for human milk and
      the potential risks.

PMID- 25847798
TI  - Prevent youth assault by assaulting firearm violence.

PMID- 25847799
TI  - Two Case Reports of Successful Treatment of Cholestasis With Steroids in Patients
      With PFIC-2.
AB  - Mutations in the gene encoding the canalicular bile salt export pump (BSEP) can
      result in progressive familial intrahepatic cholestasis type 2 (PFIC-2).
      Treatment options are limited, and PFIC-2 often necessitates liver
      transplantation. We report on a young woman and a boy who clinically presented
      with PFIC-2 phenotypes and dramatically improved with steroid treatment. Gene
      sequencing of ABCB11 encoding for BSEP revealed 2 relevant mutations in both
      patients. The young woman was compound heterozygous for p.T919del and p.R1235X.
      At the age of 5 years, partial biliary diversion was performed and rescued liver
      function but left serum bile salt levels elevated. At age 23 she developed
      systemic lupus erythematosus. Unexpectedly, steroid therapy normalized serum bile
      salt levels, with a strong correlation with the steroid dose. She is currently in
      clinical remission. The boy was compound heterozygous for the ABCB11 mutations
      c.150+3A>C and p.R832C and presented with intractable pruritus. When he developed
      colitis, he was treated with steroids. The pruritus completely disappeared and
      relapsed when steroids were withdrawn. To date, with low-dose budesonide, the boy
      has been symptom-free for >3 years. In conclusion, the clinical courses suggest
      that patients with BSEP deficiency and residual BSEP activity may benefit from
      steroid-based therapy, which represents a new treatment option. 

PMID- 25847800
TI  - Competency in neonatal endotracheal intubation: mission impossible?

PMID- 25847801
TI  - Parental hope for children with advanced cancer.
AB  - BACKGROUND: Previous work suggests that parents of children with cancer can
      remain hopeful despite receiving prognostic information, but we know little about
      what hope means to such parents, or the extent to which parents can feel hopeful
      even while facing the child's impending death. METHODS: We audiotaped
      conversations between clinicians and parents of 32 children with relapsed or
      refractory cancer, and then interviewed parents about their hopes and
      expectations for their child. RESULTS: Parent statements about prognosis in
      interviews mirrored those made by clinicians during discussions about the child's
      diagnosis with refractory or relapsed cancer. Clinicians used language referring
      to hope during these conversations but did not ask parents directly about their
      hopes. Parents expressed a range of hopes for their children, from hopes related
      to cure or treatment response, to quality of life, normalcy, and love and
      relationships for the child. For most parents, expectations about prognosis were
      not aligned with their hopes for the child; for example, many parents hoped for a
      cure and also reported that they did not believe cure was possible. Many parents
      were able to acknowledge this incongruence. CONCLUSIONS: Parents accurately
      conveyed the reality of their child's serious condition in the setting of
      advanced cancer, and yet maintained hope. Hopes were not limited to hope for
      cure/treatment response. Clinicians should be encouraged to engage in direct
      conversations about hope with parents as a means to elicit realistic hopes that
      can help to focus the most meaningful plans for the child and family.

PMID- 25847802
TI  - Two infants, same prognosis, different parental preferences.
AB  - A central principle of justice is that similar cases should be decided in similar
      ways. In pediatrics, however, there are cases in which 2 infants have similar
      diagnoses and prognoses, but their parents request different treatments. In this
      Ethics Rounds, we present such a situation that occurred in a single NICU. Three
      physician-ethicists analyze the issues. 

PMID- 25847803
TI  - Nicotine replacement therapy in pregnancy and major congenital anomalies in
      offspring.
AB  - BACKGROUND AND OBJECTIVES: Nicotine replacement therapy (NRT) is now being used
      as a smoking cessation aid during pregnancy, although little is known about fetal
      safety. We assessed the relationship between early pregnancy exposure to NRT or
      smoking with major congenital anomalies (MCA) in offspring. METHODS: We studied
      192,498 children born in the United Kingdom between 2001 and 2012 with linked
      mother-child primary care records. The absolute risks of MCAs in the NRT group
      (women prescribed NRT during the first trimester or 1 month before conception
      [and therefore likely consumed during the first trimester]) and odds ratios (ORs)
      and 99% confidence intervals (CIs) were compared with those of women who smoked
      during pregnancy and with a control group (women who neither smoked nor were
      prescribed NRT); logistic regression models adjusted for maternal morbidities
      that increase MCA risk were used for analysis. RESULTS: MCA prevalence was 288
      per 10,000 live births (5535 children with >= 1 MCA). Maternal morbidities were
      most common in the NRT group (35%) followed by smokers (27%) and the control
      group (20%). Compared with the control group, adjusted ORs for MCAs in the NRT
      group and smokers were 1.12 (99% CI: 0.84-1.48) and 1.05 (99% CI: 0.89-1.23),
      respectively. The OR comparing the NRT group directly with smokers was 1.07 (99%
      CI: 0.78-1.47). There were no statistically significant associations between
      maternal NRT and system-specific anomalies except for respiratory anomalies (OR:
      4.65 [99% CI: 1.76-12.25]; absolute risk difference: 3 per 1000 births), which
      was based on 10 exposed cases. CONCLUSIONS: For most system-specific MCAs, we
      found no statistically significant increased risks associated with maternal NRT
      prescribed during pregnancy, except for respiratory anomalies. Although this
      study is the largest published to date, NRT use in pregnancy remains rare; thus,
      the statistical power was limited. Higher morbidities in those women prescribed
      NRT may also be an explanatory factor. Nevertheless, absolute MCA risks were
      similar between women who smoked and those prescribed NRT during pregnancy.

PMID- 25847804
TI  - Validity of the strengths and difficulties questionnaire in preschool-aged
      children.
AB  - BACKGROUND: The Strengths and Difficulties Questionnaire (SDQ) is widely used to
      screen for child mental health problems and measure common forms of
      psychopathology in 4- to 16-year-olds. Using longitudinal data, we examined the
      validity of a version adapted for 3- to 4-year-olds. METHODS: We used SDQ data
      from 16,659 families collected by the Millennium Cohort Study, which charts the
      development of children born throughout the United Kingdom during 2000-2001.
      Parents completed the preschool SDQ when children were aged 3 and the standard
      SDQ at ages 5 and 7. The SDQ's internal factor structure was assessed by using
      confirmatory factor analysis, with a series of competing models and extensions
      used to determine construct, convergent, and discriminant validity and
      measurement invariance over time. Predictive validity was evaluated by examining
      the relationships of age 3 SDQ scores with age 5 diagnostic measures of attention
      deficit/hyperactivity disorder, autism spectrum disorder/Asperger syndrome, and
      teacher-reported measures of personal, social, and emotional development.
      RESULTS: Confirmatory factor analysis supported a 5-factor measurement model.
      Internal reliability of subscales ranged from omega = 0.66 (peer problems) to
      omega = 0.83 (hyperactivity). Item-factor structures revealed measurement
      invariance over time. Strong positive correlations between ages 3 and 5 SDQ
      scores were not significantly different from correlations between age 5 and 7
      scores. Conduct problems and hyperactivity subscales independently predicted
      developmental and clinical outcomes 2 years later. CONCLUSIONS: Satisfactory
      psychometric properties of the adapted preschool version affirm its utility as a
      screening tool to identify 3- to 4-year-olds with emotional and behavioral
      difficulties.

PMID- 25847805
TI  - Predicting neonatal intubation competency in trainees.
AB  - BACKGROUND AND OBJECTIVES: Pediatric residency training programs are graduating
      residents who are not competent in neonatal intubation, a vital skill needed for
      any pediatrician involved in delivery room resuscitations. However, a precise
      definition of competency during training is lacking. The objective of this study
      was to more precisely define the trajectory toward competency in neonatal
      intubation for pediatric residents, as a framework for later evaluating
      complementary training tools. METHODS: This is a retrospective single-center
      observational study of resident-performed neonatal intubations at Duke University
      Medical Center between 2005 and 2013. Using a Bayesian statistical model,
      intubation competency was defined when the resident attained a 75% likelihood of
      intubating their next patient successfully. RESULTS: A total of 477 unique
      intubation attempts by 105 residents were analyzed. The path to proficiency was
      defined by a categorical or milestone learning event after which all learners
      move toward competency in a similar manner. In our cohort, 4 cumulative successes
      were needed to achieve competency. Only 24 of 105 (23%) achieved competency
      during the study period. Residents who failed their first 2 opportunities,
      compared with those successful on their first 2 opportunities, needed nearly
      double the intubation exposure to achieve competency. CONCLUSIONS: Bayesian
      statistics may be useful to more precisely describe neonatal intubation
      competency in residents. Achieving competency in neonatal intubation appears to
      be a categorical or milestone learning event whose timing varies between
      residents. The current educational environment does not provide adequate
      procedural exposure to achieve competency for most residents.

PMID- 25847806
TI  - Linear growth and child development in low- and middle-income countries: a meta
      analysis.
AB  - BACKGROUND AND OBJECTIVE: The initial years of life are critical for physical
      growth and broader cognitive, motor, and socioemotional development, but the
      magnitude of the link between these processes remains unclear. Our objective was
      to produce quantitative estimates of the cross-sectional and prospective
      association of height-for-age z score (HAZ) with child development. METHODS:
      Observational studies conducted in low- and middle-income countries (LMICs)
      presenting data on the relationship of linear growth with any measure of child
      development among children <12 years of age were identified from a systematic
      search of PubMed, Embase, and PsycINFO. Two reviewers then extracted these data
      by using a standardized form. RESULTS: A total of 68 published studies conducted
      in 29 LMICs were included in the final database. The pooled adjusted standardized
      mean difference in cross-sectional cognitive ability per unit increase in HAZ for
      children <= 2 years old was +0.24 (95% confidence interval [CI], 0.14-0.33; I(2)
      = 53%) and +0.09 for children > 2 years old (95% CI, 0.05-0.12; I(2) = 78%).
      Prospectively, each unit increase in HAZ for children <= 2 years old was
      associated with a +0.22-SD increase in cognition at 5 to 11 years after
      multivariate adjustment (95% CI, 0.17-0.27; I(2) = 0%). HAZ was also
      significantly associated with earlier walking age and better motor scores (P <
      .05). CONCLUSIONS: Observational evidence suggests a robust positive association
      between linear growth during the first 2 years of life with cognitive and motor
      development. Effective interventions that reduce linear growth restriction may
      improve developmental outcomes; however, integration with environmental,
      educational, and stimulation interventions may produce larger positive effects.

PMID- 25847807
TI  - Safely doing less and the new AAP bronchiolitis guideline.

PMID- 25847809
TI  - The development or exacerbation of eating disorder symptoms after topiramate
      initiation.
AB  - The Food and Drug Administration recently approved topiramate for migraine
      prevention in adolescents. Given the well-established appetite-suppressant side
      effects of topiramate, as well as data suggesting a potential comorbidity between
      migraine and eating disorders, susceptible young migraine patients may be at a
      greater risk for the development or worsening of eating disorder symptoms with
      topiramate therapy. This case series comprises 7 adolescent patients in whom
      serious eating disorders developed or were exacerbated after the initiation of
      topiramate therapy. Clinical characteristics of these patients are highlighted.
      In addition, this case series provides guidelines for providers to use in
      assessing eating disorders before prescribing topiramate for migraine prevention
      in adolescents. 

PMID- 25847808
TI  - Firearm violence among high-risk emergency department youth after an assault
      injury.
AB  - BACKGROUND: The risk for firearm violence among high-risk youth after treatment
      for an assault is unknown. METHODS: In this 2-year prospective cohort study, data
      were analyzed from a consecutive sample of 14- to 24-year-olds with drug use in
      the past 6 months seeking assault-injury care (AIG) at an urban level 1 emergency
      department (ED) compared with a proportionally sampled comparison group (CG) of
      drug-using nonassaulted youth. Validated measures were administered at baseline
      and follow-up (6, 12, 18, 24 months). RESULTS: A total of 349 AIG and 250 CG
      youth were followed for 24 months. During the follow-up period, 59% of the AIG
      reported firearm violence, a 40% higher risk than was observed among the CG
      (59.0% vs. 42.5%; relative risk [RR] = 1.39). Among those reporting firearm
      violence, 31.7% reported aggression, and 96.4% reported victimization, including
      19 firearm injuries requiring medical care and 2 homicides. The majority with
      firearm violence (63.5%) reported at least 1 event within the first 6 months.
      Poisson regression identified baseline predictors of firearm violence, including
      male gender (RR = 1.51), African American race (RR = 1.26), assault-injury (RR =
      1.35), firearm possession (RR = 1.23), attitudes favoring retaliation (RR =
      1.03), posttraumatic stress disorder (RR = 1.39), and a drug use disorder (RR =
      1.22). CONCLUSIONS: High-risk youth presenting to urban EDs for assault have
      elevated rates of subsequent firearm violence. Interventions at an index visit
      addressing substance use, mental health needs, retaliatory attitudes, and firearm
      possession may help decrease firearm violence among urban youth.

PMID- 25847811
TI  - How can follow-up of patients with Raynaud phenomenon be optimized?
AB  - BACKGROUND Raynaud phenomenon (RP) is common worldwide and presents diagnostic
      and therapeutic difficulties. We aimed to share our experience with optimizing of
      patient follow-up by using the cold-stimulation test (CST). MATERIAL AND METHODS
      Data of 81 patients admitted with RP symptomatology were collected. Demographic
      data and symptoms were recorded. A scale was used for determining the severity of
      disease at pre-treatment and post-treatment. CST was performed to all patients at
      pre-treatment and post-treatment for assessment of treatment efficiency in follow
      up. Results were analyzed with the SPSS for Mac 20.0 program. RESULTS All the
      patients were male. Mean age was 22.3 +/- 2.14 (19-29). Mean duration of symptoms
      from onset to present was 4.59 +/- 2.85 years. There were statistically
      significant differences between pre-treatment and post-treatment hand
      temperatures measured by CST (p<0.001). However, there were no statistically
      significant differences between pre-treatment and post-treatment severity scores
      of patients (p=0.135). CONCLUSIONS To quantitatively determine the treatment
      efficacy, CST may be used instead of asking simple questions of patients.

PMID- 25847810
TI  - Dynamics of Vibrio cholerae abundance in Austrian saline lakes, assessed with
      quantitative solid-phase cytometry.
AB  - In order to elucidate the main predictors of Vibrio cholerae dynamics and to
      estimate the risk of Vibrio cholera-related diseases, a recently developed direct
      detection approach based on fluorescence in situ hybridization and solid-phase
      cytometry (CARD-FISH/SPC) was applied in comparison to cultivation for water
      samples from the lake Neusiedler See, Austria and three shallow alkaline lakes
      over a period of 20 months. Vibrio cholerae attached to crustacean zooplankton
      was quantified via FISH and epifluorescence microscopy. Concentrations obtained
      by CARD-FISH/SPC were significantly higher than those obtained by culture in
      2011, but were mostly of similar magnitude in 2012. Maximum cell numbers were
      1.26 * 10(6) V. cholerae per L in Neusiedler See and 7.59 * 10(7) V. cholerae per
      L in the shallow alkaline lakes. Only on a few occasions during summer was the
      crustacean zooplankton the preferred habitat for V. cholerae. In winter, V.
      cholerae was not culturable but could be quantified at all sites with CARD
      FISH/SPC. Beside temperature, suspended solids, zooplankton and ammonium were the
      main predictors of V. cholerae abundance in Neusiedler See, while in the shallow
      alkaline lakes it was organic carbon, conductivity and phosphorus. Based on the
      obtained concentrations a first estimation of the health risk for visitors of the
      lake could be performed. 

PMID- 25847812
TI  - Effect of initial GnRH and duration of progesterone insert treatment on the
      fertility of lactating dairy cows.
AB  - The study compared response to prostaglandin F2alpha (PG), synchrony of ovulation
      and pregnancy per AI (P/AI) in a 5- vs a 7-day Ovsynch + PRID protocol and
      investigated whether the initial GnRH affects P/AI in lactating dairy cows. Two
      hundred and seventy-six cows (500 inseminations) were assigned to one of four
      timed-AI (TAI) protocols: (i) PRID-7G; 100 MUg GnRH im, and a progesterone
      releasing intravaginal device (PRID) for 7 days. At PRID removal, PG (500 MUg of
      cloprostenol) was given im. Cows received the second GnRH treatment at 60 h after
      PRID removal and TAI 12 h later. (ii) PRID-5G; as PRID-7G except the duration of
      PRID, treatment was 5 days and PG was given twice (12 h apart). (iii) PRID-7NoG;
      as PRID-7G except the initial GnRH, treatment was omitted. (iv) PRID-5NoG; as
      PRID-7NoG except the duration of PRID, treatment was 5 days. Response to
      treatments and pregnancy status at 32 and 60 days after TAI was determined by
      ultrasonography. The percentage of cows ovulating before TAI was greatest in PRID
      7G (17.1%), and the percentage of cows that did not have luteal regression was
      greatest in PRID-5G (9.5%). The overall P/AI at 32 and 60 days did not differ
      among TAI protocols. However, during resynchronization, cows subjected to the 5
      day protocols had greater (p < 0.05) P/AI (45.3% vs 33.6%) than cows subjected to
      the 7-day protocols. Pregnancy loss between 32 and 60 days tended (p = 0.10) to
      be greater in cows that did not receive initial GnRH (14.8%) compared to those
      that received GnRH (8.2%). In conclusion, the PRID-5G protocol resulted in fewer
      cows responding to PG, but P/AI did not differ among TAI protocols. A 5-day
      protocol resulted in more P/AI in resynchronized cows, and cows that did not
      receive initial GnRH tended to experience more pregnancy losses. 

PMID- 25847813
TI  - Economic level and human longevity: Spatial and temporal variations and
      correlation analysis of per capita GDP and longevity indicators in China.
AB  - OBJECTIVE: We show the variation of longevity indicators in China during the past
      60 years and its correlation patterns with per capita GDP (GDPpc) both at
      provincial and inner-provincial level. METHODS: Population data from six national
      population censuses in China (1953-2010) at provincial level and in several
      typical provinces in 2010 at county-level were selected. Four main longevity
      indicators were calculated. Pearson's r and distributed lags time series analysis
      between longevity indicators and GDPpc were conducted. RESULTS: The results show
      that Guangxi and Hainan Provinces maintain relatively high long-lived population
      (population over the age of 90) across various population censuses. The
      distributions of the population over the age of 80 and life expectancy are
      significantly affected by both contemporaneous and historical GDPpc at provincial
      level. However, areas of high long-lived population (over the age of 90) exhibit
      continuously stable features that lack any significant correlation with GDPpc
      both at provincial and inner-provincial level. CONCLUSION: Our results indicate a
      mixed distribution pattern of several longevity indexes and different relation to
      GDPpc. It shows consistent trend with Preston curve, that is, economic conditions
      may have limited influence on human longevity, especially for those who live
      longer than 90 years old. This study suggests that the economic development may
      favor the local residents to have access to live as old as 80 years old, but it
      is still difficult for most residents to reach the level of centenarians.

PMID- 25847814
TI  - One-Pot Synthesis of 5-Amino-2,5-dihydro-1-benzoxepines: Access to
      Pharmacologically Active Heterocyclic Scaffolds.
AB  - A one-pot multibond-forming process involving a thermally mediated Overman
      rearrangement and a ring closing metathesis reaction of allylic
      trichloroacetimidates bearing a 2-allyloxyaryl group has been developed for the
      synthesis of 5-amino-substituted 2,5-dihydro-1-benzoxepines. Chemoselective
      reduction and functionalization of these compounds allowed access to a range of
      pharmacologically active 5-amino-2,3,4,5-tetrahydro-1-benzoxepine scaffolds. 

PMID- 25847816
TI  - Scandium-catalyzed asymmetric 1,6-addition of 3-substituted oxindoles to linear
      dienyl ketones.
AB  - The first example of a N,N'-dioxide-Sc(III) -catalyzed 1,6-addition of 3
      substituted oxindoles to dienyl ketones has been developed. This procedure
      tolerates a relatively wide range of 3-substituted oxindoles under mild
      conditions, facilitating the preparation of various chiral oxindoles with
      quaternary stereocenters. In addition, the reliable catalyst was found to be
      effective in the asymmetric 1,6-addition of both delta-unsubstituted and delta
      methyl-substituted dienyl ketones, achieving excellent regioselectivities and
      enantioselectivities (up to>99 % ee). 

PMID- 25847815
TI  - What is the function of mitochondrial networks? A theoretical assessment of
      hypotheses and proposal for future research.
AB  - Mitochondria can change their shape from discrete isolated organelles to a large
      continuous reticulum. The cellular advantages underlying these fused networks are
      still incompletely understood. In this paper, we describe and compare hypotheses
      regarding the function of mitochondrial networks. We use mathematical and
      physical tools both to investigate existing hypotheses and to generate new ones,
      and we suggest experimental and modelling strategies. Among the novel insights we
      underline from this work are the possibilities that (i) selective mitophagy is
      not required for quality control because selective fusion is sufficient; (ii)
      increased connectivity may have non-linear effects on the diffusion rate of
      proteins; and (iii) fused networks can act to dampen biochemical fluctuations. We
      hope to convey to the reader that quantitative approaches can drive advances in
      the understanding of the physiological advantage of these morphological changes. 

PMID- 25847817
TI  - Changes in nutrient composition and in vitro ruminal fermentation of total mixed
      ration silage stored at different temperatures and periods.
AB  - BACKGROUND: Total mixed ration (TMR) is widely used for dairy cattle and needs to
      be prepared daily because it deteriorates rapidly. Ensiling TMR allows
      preservation and saves labour at the farm; however, silage fermentation may
      influence various nutritional components. The objectives of this study were to
      evaluate nutritional changes and in vitro rumen fermentation of TMR silage that
      was stored at different temperatures and durations on a laboratory scale in
      comparison with those of typical TMR before ensiling. RESULTS: No distinct
      changes in crude protein (CP), neutral detergent fibre and non-fibrous
      carbohydrate contents were observed during silage fermentation. However, clear
      changes were observed in the soluble CP and soluble sugar fractions;
      solubilisation of the CP fraction in TMR silage was enhanced by prolonged storage
      and higher storage temperatures, and most soluble sugars were lost during
      ensiling. Short-chain fatty acid concentrations in the in vitro rumen from TMRs
      before and after ensiling were not significantly different; however, throughout
      incubation, NH3 -N concentrations from TMR silages were significantly higher than
      those from TMR before ensiling. CONCLUSION: A higher ruminal NH3 -N concentration
      from TMR silage may be a result of a shortage of fermentable sugars and enhanced
      deamination of CP. Feeding TMR ensiled under a high temperature must be
      investigated to balance proteins and carbohydrates for rumen fermentation.

PMID- 25847818
TI  - The use of ketamine as an antidepressant: a systematic review and meta-analysis.
AB  - OBJECTIVE: The current meta-analysis examines the effects of ketamine infusion on
      depressive symptoms over time in major depressive disorder (MDD) and bipolar
      disorder (BD). METHODS: Following a systematic review of the literature, data
      were extracted from 21 studies (n = 437 receiving ketamine) and analysed at four
      post-infusion time points (4 h, 24 h, 7 days and 12-14 days). The moderating
      effects of several factors were assessed including: repeat/single infusion,
      diagnosis, open-label/participant-blind infusion, pre-post/placebo-controlled
      design and the sex of patients. RESULTS: Effect sizes were significantly larger
      for repeat than single infusion at 4 h, 24 h and 7 days. For single infusion
      studies, effect sizes were large and significant at 4 h, 24 h and 7 days. The
      percentage of males was a predictor of antidepressant response at 7 days. Effect
      sizes for open-label and participant-blind infusions were not significantly
      different at any time point. CONCLUSIONS: Single ketamine infusions elicit a
      significant antidepressant effect from 4 h to 7 days; the small number of studies
      at 12-14 days post infusion failed to reach significance. Results suggest a
      discrepancy in peak response time depending upon primary diagnosis - 24 h for MDD
      and 7 days for BD. The majority of published studies have used pre-post
      comparison; further placebo-controlled studies would help to clarify the effect
      of ketamine over time.

PMID- 25847820
TI  - Biomolecular bases of the senescence process and cancer. A new approach to
      oncological treatment linked to ageing.
AB  - Human ageing is associated with a gradual decline in the physiological functions
      of the body at multiple levels and it is a key risk factor for many diseases,
      including cancer. Ageing process is intimately related to widespread cellular
      senescence, characterised by an irreversible loss of proliferative capacity and
      altered functioning associated with telomere attrition, accumulation of DNA
      damage and compromised mitochondrial and metabolic function. Tumour and senescent
      cells may be generated in response to the same stimuli, where either cellular
      senescence or transformation would constitute two opposite outcomes of the same
      degenerative process. This paper aims to review the state of knowledge on the
      biomolecular relationship between cellular senescence, ageing and cancer.
      Importantly, many of the cell signalling pathways that are found to be altered
      during both cellular senescence and tumourigenesis are regulated through shared
      epigenetic mechanisms and, therefore, they are potentially reversible. MicroRNAs
      are emerging as pivotal players linking ageing and cancer. These small RNA
      molecules have generated great interest from the point of view of future clinical
      therapy for cancer because successful experimental results have been obtained in
      animal models. Micro-RNA therapies for cancer are already being tested in
      clinical phase trials. These findings have potential importance in cancer
      treatment in aged people although further research-based knowledge is needed to
      convert them into an effective molecular therapies for cancer linked to ageing.

PMID- 25847821
TI  - A case of empyema and a posterior mediastinal abscess after an iliopsoas abscess
      secondary to Crohn's disease.

PMID- 25847819
TI  - Preliminary patient-reported outcomes analysis of 3-dimensional radiation therapy
      versus intensity-modulated radiation therapy on the high-dose arm of the
      Radiation Therapy Oncology Group (RTOG) 0126 prostate cancer trial.
AB  - BACKGROUND: The authors analyzed a preliminary report of patient-reported
      outcomes (PROs) among men who received high-dose radiation therapy (RT) on
      Radiation Therapy Oncology Group study 0126 (a phase 3 dose-escalation trial)
      with either 3-dimensional conformal RT (3D-CRT) or intensity-modulated RT (IMRT).
      METHODS: Patients in the 3D-CRT group received 55.8 gray (Gy) to the prostate and
      proximal seminal vesicles and were allowed an optional field reduction; then,
      they received 23.4 Gy to the prostate only. Patients in the IMRT group received
      79.2 Gy to the prostate and proximal seminal vesicles. PROs were assessed at 0
      months (baseline), 3 months, 6 months, 12 months, and 24 months and included
      bladder and bowel function assessed with the Functional Alterations due to
      Changes in Elimination (FACE) instrument and erectile function assessed with the
      International Index of Erectile Function (IIEF). Analyses included the patients
      who completed all data at baseline and for at least 1 follow-up assessment, and
      the results were compared with an imputed data set. RESULTS: Of 763 patients who
      were randomized to the 79.2-Gy arm, 551 patients and 595 patients who responded
      to the FACE instrument and 505 patients and 577 patients who responded to the
      IIEF were included in the completed and imputed analyses, respectively. There
      were no significant differences between modalities for any of the FACE or IIEF
      subscale scores or total scores at any time point for either the completed data
      set or the imputed data set. CONCLUSIONS: Despite significant reductions in dose
      and volume to normal structures using IMRT, this robust analysis of 3D-CRT and
      IMRT demonstrated no difference in patient-reported bowel, bladder, or sexual
      functions for similar doses delivered to the prostate and proximal seminal
      vesicles with IMRT compared with 3D-CRT delivered either to the prostate and
      proximal seminal vesicles or to the prostate alone.

PMID- 25847822
TI  - Sphincter-sparing intersphincteric rectal resection as an alternative to
      proctectomy in long-standing fistulizing and stenotic Crohn's proctitis?
AB  - PURPOSE: Long-standing fistulizing and stenotic proctitis (LFSP) in Crohn's
      disease (CD) indicates the end stage of the disease. Definitive diversion such as
      proctectomy is considered to be the only surgical option. The impact of
      intersphincteric sphincter-sparing anterior rectal resection (IAR) as an
      alternative to proctectomy is unclear. The aim of this study was to evaluate
      feasibility, morbidity, outcome, and quality of life (QL) in patients with LFSP
      undergoing intended IAR. PATIENTS AND METHODS: Out of a single institution
      database, 15 patients with LFSP intended for surgery from 856 patients with CD
      were selected for follow-up analyses. RESULTS: In 12/15 cases, IAR was carried
      out while 3/15 patients underwent primary proctectomy due to malignancy (n = 2)
      or due to patient's wish (n = 1). In one case, IAR revealed unexpected
      malignancy, which led to secondary proctectomy. In patients with IAR, complete
      healing of fistulas and stenosis was observed in 46% (n = 5) while 36% (n = 4) of
      patients showed relapse of fistula and 18% (n = 2) developed restenosis.
      Ileostomy closure was performed in seven patients from which six patients
      remained stoma free. QL and fecal incontinence measured by standardized scoring
      systems were unchanged while stool frequency was reduced after IAR in patients
      with ileostomy closure. The rate of malignancy in this cohort was 20% (n = 3).
      CONCLUSION: LFSP in CD was associated with 20% of malignant transformation.
      Although IAR fails to improve QL, it is a suitable procedure for the treatment of
      fistulas and stenosis associated with acceptable healing rates and can avoid a
      permanent stoma.

PMID- 25847823
TI  - Letter to the editor: mistaken inheritance.

PMID- 25847824
TI  - Summary of the 2nd International Symposium on Arthrogryposis, St. Petersburg,
      Russia, September 17-19, 2014.
AB  - Enormous progress has been made in understanding the etiology and therapies for
      arthrogryposis (multiple congenital contractures). A 2nd International Symposium
      on Arthrogryposis was sponsored by the Turner Institute in St. Petersburg,
      Russia. Olga Agranovich, Head of the Arthrogryposis Department of the Turner
      Institute, organized this special meeting. Care providers from multiple
      disciplines from all over the world representing 18 nations attended.
      Participants included: Pediatric orthopedic specialists, rehabilitation
      physicians, occupational therapists, physical therapists, medical geneticists,
      neurologists, craniofacial physicians, psychologists, developmental biologists,
      as well as representatives from parent support groups. The 1st symposium
      established the need for a collaborative and interdisciplinary approach to the
      treatment of arthrogryposis, engagement of parent support organizations, and the
      aim for more research. The Second Symposium highlighted the continuing need for
      more research on various therapies, identification of different types of
      arthrogryposis, standardized descriptions of severity, development of new
      orthotics, improved prenatal diagnosis, and studying adult outcome. Major
      progress has been made on both upper and lower limb treatments.

PMID- 25847825
TI  - Selection and evolutionary potential of spring arrival phenology in males and
      females of a migratory songbird.
AB  - The timing of annual life-history events affects survival and reproduction of all
      organisms. A changing environment can perturb phenological adaptations and an
      important question is if populations can evolve fast enough to track the
      environmental changes. Yet, little is known about selection and evolutionary
      potential of traits determining the timing of crucial annual events. Migratory
      species, which travel between different climatic regions, are particularly
      affected by global environmental changes. To increase our understanding of
      evolutionary potential and selection of timing traits, we investigated the
      quantitative genetics of arrival date at the breeding ground using a
      multigenerational pedigree of a natural great reed warbler (Acrocephalus
      arundinaceus) population. We found significant heritability of 16.4% for arrival
      date and directional selection for earlier arrival in both sexes acting through
      reproductive success, but not through lifespan. Mean arrival date advanced with 6
      days over 20 years, which is in exact accordance with our predicted evolutionary
      response based on the breeder's equation. However, this phenotypic change is
      unlikely to be caused by microevolution, because selection seems mainly to act on
      the nongenetic component of the trait. Furthermore, demographical changes could
      also not account for the advancing arrival date. Instead, a strong correlation
      between spring temperatures and population mean arrival date suggests that
      phenotypic plasticity best explains the advancement of arrival date in our study
      population. Our study dissects the evolutionary and environmental forces that
      shape timing traits and thereby increases knowledge of how populations cope with
      rapidly changing environments.

PMID- 25847826
TI  - [Preterm rupture of membranes: Is home care a safe management?].
AB  - OBJECTIVE: Compare the maternal and neonatal outcomes in pregnancies complicated
      by preterm prelabour rupture of membranes (PPROM), which were managed either at
      home (HAD) or hospital (HC). MATERIALS AND METHODS: Retrospective study in two
      level III maternities during 2 years. Inclusion criteria in HAD were: singleton
      pregnancy, PPROM between 24 and 35 weeks of gestation, absence of
      chorioamnionitis, clinical stability at D7 of the rupture, cervical dilatation <3
      cm, patient residing in the geographic area. RESULTS: Thirty-two patients were
      included in the HAD group and 24 in the HC group. Our populations were similar in
      the 2 groups. The duration of latency was longer in the HAD group than in the HC
      group (27.5 d [20-37] versus 16.5 d [12.5 to 29.5]; P=0.026). Patients in the HAD
      group received fewer antibiotics with a similar rate of chorioamnionitis. No
      difference in terms of obstetrical and neonatal outcomes was observed. Number of
      days in neonatal resuscitation was lower in the HAD group than in the HC group
      (12.5 d [10-22] versus 43 d [20-52]; P=0.003). CONCLUSION: HAD seems to be an
      alternative to continuous hospitalization for patients followed for PPROM between
      24 and 35 weeks. A randomized study with a larger number of patients, including
      other data such as maternal satisfaction and cost analysis, would be interesting
      to confirm those preliminary results.

PMID- 25847835
TI  - Distinct pathways for norepinephrine- and opioid-triggered antinociception from
      the amygdala.
AB  - BACKGROUND: The amygdala has an important role in pain and pain modulation. We
      showed previously in animal studies that alpha2 -adrenoreceptor activation in the
      central nucleus of the amygdala (CeA) mediates hypoalgesia produced by restraint
      stress, and that direct application of an alpha2 -agonist in this region produces
      analgesia. AIMS: In the present animal experiments, we investigated the pathways
      through which alpha2 -sensitive systems in the CeA produce behavioural analgesia.
      The CeA has dense connections to a descending pain modulatory network, centred in
      the midbrain periaqueductal grey (PAG) and the rostral ventromedial medulla
      (RVM), which is implicated in various forms of stress-related hypoalgesia and
      which mediates the antinociceptive effect of morphine applied in the basolateral
      amygdala. We investigated whether this circuit mediates the hypoalgesic effects
      of alpha2 -adrenergic agonist administration into the CeA as well as the
      contribution of endogenous opioids and cannabinoids. We also tested the
      possibility that activation of alpha2 -receptors in the CeA produces
      antinociception by recruitment of noradrenergic pathways projecting to the spinal
      cord. RESULTS: Hypoalgesia resulting from bilateral application of the alpha2 
      adrenergic agonist clonidine in the CeA was not reversed by chemical inactivation
      of the RVM or by systemic injections of naloxone (MU-opioid antagonist) or
      rimonabant (CB1 antagonist). By contrast, spinal alpha2 -receptor blockade
      (intrathecal idazoxan) completely prevented the hypoalgesic effect of clonidine
      in the CeA, and unmasked a small but significant hyperalgesia. CONCLUSION: In
      rats, adrenergic actions in the CeA mediating hypoalgesia require spinal
      adrenergic neurotransmission but not the PAG-RVM pain modulatory network, or
      opiate or cannabinoid systems.

PMID- 25847836
TI  - Evidence of a target resistance to antivitamin K rodenticides in the roof rat
      Rattus rattus: identification and characterisation of a novel Y25F mutation in
      the Vkorc1 gene.
AB  - BACKGROUND: In spite of intensive use of bromadiolone, rodent control was
      inefficient on a farm infested by rats in Zaragoza, Spain. While metabolic
      resistance was previously described in this rodent species, the observation of a
      target resistance to antivitamin K rodenticides had been poorly documented in
      Rattus rattus. RESULTS: From rats trapped on the farm, cytochrome b and Vkorc1
      genes were amplified by PCR and sequenced in order to identify species and detect
      potential Vkorc1 mutations. VKORC1-deduced amino acid sequences were thus
      expressed in Pichia pastoris, and inhibition constants towards various
      rodenticides were determined. The ten rats trapped on the farm were all
      identified as R. rattus. They were found to be homozygous for the g.74A>T
      nucleotide replacement in exon 1 of the Vkorc1 gene, leading to p.Y25F mutation.
      This mutation led to increased apparent inhibition constants towards various
      rodenticides, probably caused by a partial loss of helical structure of TM4.
      CONCLUSION: The p.Y25F mutation detected in the Vkorc1 gene in R. rattus trapped
      on the Spanish farm is associated with the resistance phenotype to bromadiolone
      that has been observed. It is the first evidence of target resistance to
      antivitamin K anticoagulants in R. rattus.

PMID- 25847837
TI  - The Cardioprotective Effect of Icariin on Ischemia-Reperfusion Injury in Isolated
      Rat Heart: Potential Involvement of the PI3K-Akt Signaling Pathway.
AB  - AIMS: Icariin (ICA), a flavonoid isolated from epimedii, has been reported to
      have potential protective effects on the cardiovascular system. This study is to
      investigate the effect and the underlying mechanisms of ICA on
      ischemia/reperfusion (I/R) injury. METHODS: Wister rat hearts were subjected to
      I/R using Langendorff perfusion system. Cardiac function, myocardial infarct
      size, lactate dehydrogenase (LDH), and creatine kinase-MB (CK-MB) activities in
      coronary effluent, and superoxide dismutase (SOD) and malondialdehyde (MDA)
      content in heart tissue and cardiomyocyte apoptosis were assayed. RESULTS:
      Compared with the I/R group, ICA treatment significantly improved cardiac
      function, decreased myocardial infarct size, enzyme activity, oxidative stress,
      and apoptosis. In addition, ICA treatment lead to an increased p-Akt level, which
      was partially reversed by LY294002, a PI3K pathway inhibitor. CONCLUSION: Our
      study suggests that ICA has a cardioprotective effect against I/R injury, which
      is associated with its antioxidative and anti-apoptotic effect, at least
      partially, through the activation of PI3K-Akt signaling pathway.

PMID- 25847838
TI  - Fingerprinting profile of polysaccharides from Lycium barbarum using multiplex
      approaches and chemometrics.
AB  - Techniques including ultraviolet-visible spectra (UV), high performance size
      exclusion chromatography (HPSEC), Fourier-transform infrared spectroscopy (FT-IR)
      and pre-column derivatization high-performance liquid chromatography (PCD-HPLC)
      were used in the fingerprinting analysis of Lycium barbarum polysaccharides
      (LBPs) from different locations and varieties. Multiple fingerprinting profiles
      were used to evaluate the similarity and classification of different LBPs with
      the help of chemometrics. The results indicated that sixteen batches of LBPs had
      good consistency, and fingerprinting techniques were simple and robust for
      quality control of LBPs as well as related products. In addition, fingerprinting
      techniques combined with chemometrics could also be used to identify different
      cultivation locations of LBPs samples. Finally, four monosaccharides
      (galacturonic acid, glucose, galactose and arabinose) and the absorptions of
      stretching vibration of ester carbonyl groups as well as NH variable angle
      vibration of -CONH- could be selected as herbal markers to distinguish different
      samples.

PMID- 25847839
TI  - Alginate-based hydrogels with improved adhesive properties for cell
      encapsulation.
AB  - Hydrogel-based biomaterials are ideal scaffolding matrices for
      microencapsulation, but they need to be modified to resemble the mechanical,
      structural and chemical properties of the native extracellular matrix. Here, we
      compare the mechanical properties and the degradation behavior of unmodified and
      modified alginate hydrogels in which cell adhesive functionality is conferred
      either by blending or covalently cross-linking with gelatin. Furthermore, we
      measure the spreading and proliferation of encapsulated osteoblast-like MG-63
      cells. Alginate hydrogels covalently crosslinked with gelatin show the highest
      degree of cell adhesion, spreading, migration, and proliferation, as well as a
      faster degradation rate, and are therefore a particularly suitable material for
      microencapsulation. 

PMID- 25847840
TI  - High-temporal velocity-encoded MRI for the assessment of left ventricular inflow
      propagation velocity: Comparison with color M-mode echocardiography.
AB  - PURPOSE: To develop an alternative method for Vp-assessment using high-temporal
      velocity-encoded magnetic resonance imaging (VE-MRI). Left ventricular (LV)
      inflow propagation velocity (Vp) is considered a useful parameter in the complex
      assessment of LV diastolic function and is measured by Color M-mode
      echocardiography. MATERIALS AND METHODS: A total of 43 patients diagnosed with
      ischemic heart failure (61 +/- 11 years) and 22 healthy volunteers (29 +/- 13
      years) underwent Color M-mode echocardiography and VE-MRI to assess the inflow
      velocity through the mitral valve (mean interexamination time 14 days). Temporal
      resolution of VE-MRI was 10.8-11.8 msec. Local LV inflow velocity was sampled
      along a 4-cm line starting from the tip of the mitral leaflets and for
      consecutive sample points the point-in-time was assessed when local velocity
      exceeded 30 cm/s. From the position-time relation, Vp was calculated by both the
      difference quotient (Vp-MRI-DQ) as well as from linear regression (Vp-MRI-LR).
      RESULTS: Good correlation was found between Vp-echo and both Vp-MRI-DQ (r = 0.83,
      P < 0.001) and Vp-MRI-LR (r = 0.84, P < 0.001). Vp-MRI showed a significant but
      small underestimation as compared to Vp measured by echocardiography (Vp-MRI-DQ:
      5.5 +/- 16.2 cm/s, P = 0.008; Vp-MRI-LR: 9.9 +/- 15.2 cm/s, P < 0.001). Applying
      age-related cutoff values for Vp to identify LV impaired relaxation, kappa
      agreement with echocardiography was 0.72 (P < 0.001) for Vp-MRI-DQ and 0.69 (P <
      0.001) for Vp-MRI-LR. CONCLUSION: High temporal VE-MRI represents a novel
      approach to assess Vp, showing good correlation with Color M-mode
      echocardiography. In healthy subjects and patients with ischemic heart failure,
      this new method demonstrated good agreement with echocardiography to identify LV
      impaired relaxation.

PMID- 25847841
TI  - Osteopontin expression in biopsies of calciphylaxis.
AB  - BACKGROUND: Calciphylaxis combines features of vascular thrombotic occlusion and
      endoluminal calcification. In this study we examine the expression of osteopontin
      as a diagnostic marker and its role in lesional pathogenesis. METHODS: 25
      formalin-fixed, paraffin embedded skin biopsies of 20 females and 5 males (mean
      age of 60 years) with a diagnosis of calciphylaxis were assessed for osteopontin
      expression. RESULTS: Lower extremities were the most commonly involved areas;
      however a truncal and genital distribution was also noted in 3 cases. Renal
      failure was present in 21 of 25 cases. One patient had myeloproliferative
      disorder and one patient had advanced colon cancer. The dominant pathology was
      localized to the subcutaneous fat, characterized by mural calcification and
      luminal thrombosis affecting capillaries, venules, arterioles and small arteries.
      In 2 cases, a subcutaneous thrombogenic vasculopathy without calcification was
      noted. Osteopontin expression was confined to the subcutis, being most striking
      in calcified vessels but also apparent in vessels without calcification,
      including mineral poor variants of calciphylaxis. CONCLUSION: Calciphylaxis
      represents a unique calcific thrombogenic vasculopathy, not limited to renal
      failure. Ectopic osteopontin expression may define a critical and initial event
      in the calciphylaxis pathogenesis. Therapeutic agents designed to reduce
      osteopontin expression may be of value in its treatment.

PMID- 25847842
TI  - The lithic industry of Sima del Elefante (Atapuerca, Burgos, Spain) in the
      context of Early and Middle Pleistocene technology in Europe.
AB  - This paper presents the lithic assemblages documented at Sima del Elefante (TE)
      and their importance in the context of the Early and Middle Pleistocene human
      occupation of Europe. We also study changes in human behaviour within the context
      of the palaeoenvironmental evolution of the Sierra de Atapuerca. This site has
      characteristics that are of great value for the study of human evolution. The
      lower levels of TE (Units TE7-TE14) are an essential reference for understanding
      the early stages of the colonization of Europe. The TE9c level has provided stone
      tools (Mode 1), faunal remains, and human fossils dated to 1.22 Ma (millions of
      years ago). Moreover, this is one of the few European sites with a stratigraphic
      sequence that includes remains of human occupations predating the Jaramillo
      subchron (Early Pleistocene) and from the Late Middle Pleistocene (Units TE18
      TE19). Despite this, the presence of archaeologically sterile units (TE15-17)
      prevents us from establishing a continuous relationship between the Early and
      Middle Pleistocene human settlements and, consequently, between their
      technological and behavioural differences. We can, however compare the
      technological and palaeoeconomic strategies adopted by different species of
      hominins during two key phases of the occupation of Europe. 

PMID- 25847843
TI  - Self-nanoemulsifying drug delivery system of trans-cinnamic acid: formulation
      development and pharmacodynamic evaluation in alloxan-induced type 2 diabetic rat
      model.
AB  - The objective of this study was to formulate a self-nanoemulsifying oral drug
      delivery system (SNEDDS) for the poorly water-soluble trans-Cinnamic acid (t-CA
      SNEDDS) that could be evaluated for its antihyperglycemic efficacy in comparison
      to the parent t-CA in an alloxan-induced diabetic rat model. A SNEDDS formulation
      consisting of 60% surfactant (Kolliphor EL), 10% co-surfactant (PEG 400) and 30%
      oil (isopropyl myristate) proved to be optimal. t-CA SNEDDS (80 mg/kg, p.o.), t
      CA suspension (80 mg/kg, p.o.), and Metformin Hydrochloride Tablets (230 mg/kg,
      p.o.) were administer qdfor 30 days to diabetic rats. After treatment the body
      weight of diabetic rats was increased, blood glucose levels, total cholesterol,
      and triglyceride in the serum tended to be normalized, while the levels of
      alanine aminotransferase and aspartate aminotransferase were markedly decreased.
      The effects of t-CA SNEDDS were superior to that of the t-CA suspension. The
      present study demonstrated that t-CA was effective in attenuating the effects of
      alloxan treatment and that t-CA SNEDDS with a more favorable absorption and
      enhanced bioavailability is more effective than t-CA.

PMID- 25847844
TI  - Surface Chirality of Gly-Pro Dipeptide Adsorbed on a Cu(110) Surface.
AB  - The adsorption of chiral Gly-Pro dipeptide on Cu(110) has been characterized by
      combining in situ polarization modulation infrared reflection absorption
      spectroscopy (PM-RAIRS) and X-ray photoelectron spectroscopy (XPS). The chemical
      state of the dipeptide, and its anchoring points and adsorption geometry, were
      determined at various coverage values. Gly-Pro molecules are present on Cu(110)
      in their anionic form (NH2 /COO(-)) and adsorb under a 3-point binding via both
      oxygen atoms of the carboxylate group and via the nitrogen atom of the amine
      group. Low-energy electron diffraction (LEED) and scanning tunneling microscopy
      (STM) have shown the presence of an extended 2D chiral array, sustained via
      intermolecular H-bonds interactions. Furthermore, due to the particular shape of
      the molecule, only one homochiral domain is formed, creating thus a truly chiral
      surface.

PMID- 25847845
TI  - Susceptibility to male infertility: replication study in Japanese men looking for
      an association with four GWAS-derived loci identified in European men.
AB  - PURPOSE: A previous genome-wide association study in European men identified four
      single nucleotide polymorphism (SNP) loci associated with male infertility. Our
      aim was to replicate, if possible, the association of these SNPs with Japanese
      male infertility. METHODS: We genotyped four SNPs (rs5911500, rs10246939,
      rs2059807, and rs11204546) in 517 Japanese patients with male infertility and 369
      fertile controls using SNP-specific real-time polymerase chain reaction TaqMan
      assays. Subsequently, we divided patients with male infertility into azoospermia
      (n = 417) and oligospermia subgroups (n = 70). RESULTS: The four SNPs previously
      identified in European men showed no significant association with collective male
      infertility in our Japanese cohort. However, allele frequency analysis did
      indicate a significantly higher frequency of the rs11204546 C allele of the OR2W3
      gene in the oligospermia subset of infertility patients compared with controls (p
      = 0.0037; odds ratio = 1.74; 95 % confidence interval, 1.21-2.53). CONCLUSIONS:
      Although this study was somewhat limited by overall sample size, the OR2W3 gene
      polymorphism rs11204546 was significantly associated with oligospermia in
      Japanese men, suggesting that OR2W3 might be involved in genetic susceptibility
      to Japanese male infertility as well as in European males.

PMID- 25847846
TI  - Evaluation of a SiPM array coupled to a Gd3Al2Ga3O12:Ce (GAGG:Ce) discrete
      scintillator.
AB  - PURPOSE: In this study, we present the results of the evaluation of the SensL
      ArraySL-4 photo-detector, coupled to a 6 * 6 GAGG:Ce scintillator array, with 2 *
      2 * 5 mm(3) crystal size elements for possible applications in medical imaging
      detectors with focus in PET applications. Experimental evaluation was carried out
      with (22)Na and (137)Cs radioactive sources and the parameters studied were
      energy resolution and peak to valley ratio. METHODS: ArraySL-4 is a commercially
      available, 4 * 4 array detector covering an active area of 13.4 mm(2). The
      GAGG:Ce scintillator array used in this study has 0.1 mm thickness BaSO4
      reflector material between the crystal elements. A symmetric resistive voltage
      division matrix was applied, which reduces the 16 outputs of the array to 4
      position signals. A Field Programmable Gate Array was used for triggering and
      digital processing of the signal pulses acquired using free running Analog to
      Digital Converters. RESULTS: Raw images and horizontal profiles of the 6 * 6
      GAGG:Ce scintillator array produced under 511 keV and 662 keV excitation are
      illustrated. Moreover, the energy spectra obtained with (22)Na and (137)Cs
      radioactive sources from a single 2 * 2 * 5 mm(3) GAGG:Ce scintillator are shown.
      The peak to valley ratio and the mean energy resolution values are reported.
      CONCLUSIONS: The acquired raw image of the GAGG:Ce crystal array under 511 keV
      excitation shows a clear visualization of all discrete scintillator elements with
      a mean peak to valley ratio equal to 40. The mean energy resolution was measured
      equal to 10.5% and 9% respectively under 511 keV and 662 keV irradiation.

PMID- 25847847
TI  - Causal discovery in an adult ADHD data set suggests indirect link between DAT1
      genetic variants and striatal brain activation during reward processing.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is a common and highly heritable
      disorder affecting both children and adults. One of the candidate genes for ADHD
      is DAT1, encoding the dopamine transporter. In an attempt to clarify its mode of
      action, we assessed brain activity during the reward anticipation phase of the
      Monetary Incentive Delay (MID) task in a functional MRI paradigm in 87 adult
      participants with ADHD and 77 controls (average age 36.5 years). The MID task
      activates the ventral striatum, where DAT1 is most highly expressed. A previous
      analysis based on standard statistical techniques did not show any significant
      dependencies between a variant in the DAT1 gene and brain activation [Hoogman et
      al. (2013); Neuropsychopharm 23:469-478]. Here, we used an alternative method for
      analyzing the data, that is, causal modeling. The Bayesian Constraint-based
      Causal Discovery (BCCD) algorithm [Claassen and Heskes (2012); Proceedings of the
      28th Conference on Uncertainty in Artificial Intelligence] is able to find direct
      and indirect dependencies between variables, determines the strength of the
      dependencies, and provides a graphical visualization to interpret the results.
      Through BCCD one gets an opportunity to consider several variables together and
      to infer causal relations between them. Application of the BCCD algorithm
      confirmed that there is no evidence of a direct link between DAT1 genetic
      variability and brain activation, but suggested an indirect link mediated through
      inattention symptoms and diagnostic status of ADHD. Our finding of an indirect
      link of DAT1 with striatal activity during reward anticipation might explain
      existing discrepancies in the current literature. Further experiments should
      confirm this hypothesis. (c) 2015 Wiley Periodicals, Inc.

PMID- 25847849
TI  - Improvements in Physicians' Knowledge, Difficulties, and Self-Reported Practice
      After a Regional Palliative Care Program.
AB  - CONTEXT: Although several studies have explored the effects of regional
      palliative care programs, no studies have investigated the changes in physician
      related outcomes. OBJECTIVES: The primary aims of this study were to: (1) clarify
      the changes in knowledge, difficulties, and self-reported practice of physicians
      before and after the intervention, (2) explore the potential associations between
      the level of physicians' participation in the program and outcomes, and (3)
      identify the reasons and characteristics of physicians who did not participate in
      the program. METHODS: As a part of the regional palliative care intervention
      trial, questionnaires were sent to physicians recruited consecutively to obtain a
      representative sample of each region. Physician-reported knowledge, difficulty of
      palliative care, and self-perceived practice were measured using the Palliative
      Care Knowledge Test, Palliative Care Difficulty Scale, and Palliative Care Self
      Reported Practice Scale (PCPS), respectively. The level of their involvement in
      the program and reason for non-participation were ascertained from self-reported
      questionnaires. RESULTS: The number of eligible physicians identified was 1870 in
      pre-intervention and 1763 in post-intervention surveys, and we obtained 911 and
      706 responses. Total scores of the Palliative Care Knowledge Test, PCPS, and PCPS
      were significantly improved after the intervention, with effect sizes of 0.30,
      0.52, and 0.17, respectively. Physicians who participated in workshops more
      frequently were significantly more likely to have better knowledge, less
      difficulties, and better self-reported practice. CONCLUSION: After the regional
      palliative care program, there were marked improvements in physicians' knowledge
      and difficulties. These improvements were associated with the level of
      physicians' participation in the program.

PMID- 25847848
TI  - The Accuracy of Physicians' Clinical Predictions of Survival in Patients With
      Advanced Cancer.
AB  - CONTEXT: Accurate prognoses are needed for patients with advanced cancer.
      OBJECTIVES: To evaluate the accuracy of physicians' clinical predictions of
      survival (CPS) and assess the relationship between CPS and actual survival (AS)
      in patients with advanced cancer in palliative care units, hospital palliative
      care teams, and home palliative care services, as well as those receiving
      chemotherapy. METHODS: This was a multicenter prospective cohort study conducted
      in 58 palliative care service centers in Japan. The palliative care physicians
      evaluated patients on the first day of admission and followed up all patients to
      their death or six months after enrollment. We evaluated the accuracy of CPS and
      assessed the relationship between CPS and AS in the four groups. RESULTS: We
      obtained a total of 2036 patients: 470, 764, 404, and 398 in hospital palliative
      care teams, palliative care units, home palliative care services, and
      chemotherapy, respectively. The proportion of accurate CPS (0.67-1.33 times AS)
      was 35% (95% CI 33-37%) in the total sample and ranged from 32% to 39% in each
      setting. While the proportion of patients living longer than CPS (pessimistic
      CPS) was 20% (95% CI 18-22%) in the total sample, ranging from 15% to 23% in each
      setting, the proportion of patients living shorter than CPS (optimistic CPS) was
      45% (95% CI 43-47%) in the total sample, ranging from 43% to 49% in each setting.
      CONCLUSION: Physicians tend to overestimate when predicting survival in all
      palliative care patients, including those receiving chemotherapy.

PMID- 25847850
TI  - Stercoral Perforation of the Colon: A Potentially Fatal Complication of Opioid
      Induced Constipation.
AB  - Stercoral perforation of the colon is a rare complication of constipation, and
      there have only been a few reported cases of stercoral perforation of the colon
      secondary to opioid-induced constipation. This article describes such a case in a
      cancer survivor with chronic cancer-related pain and reviews the medical/surgical
      literature on stercoral perforation of the colon. 

PMID- 25847851
TI  - Cost Savings Associated With an Inpatient Palliative Care Unit: Results From the
      First Two Years.
AB  - CONTEXT: Palliative care consultation services (PCCS) decrease costs for patients
      by matching treatments received to patients' and families' goals of care.
      However, few studies have examined the costs of a specialized palliative care
      unit (PCU). OBJECTIVES: To quantitatively describe Mount Sinai Hospital's PCU's
      first two years of operation; to examine how patient-related costs changed in the
      days before and after transfer to PCU; and to compare cost savings of PCU to
      those of PCCS. METHODS: Cost and administrative data from PCU patients from the
      first 24.5 months of our PCU's operation were analyzed. To compare costs between
      PCU and PCCS patients, we matched PCU patients to similar PCCS patients and used
      propensity scores to adjust for differences across groups. RESULTS: The PCU
      admitted 1107 patients in its first 24.5 months. Over this time frame, there was
      a statistically significant (P < 0.001) decrease in average daily direct costs
      per patient. The mean of patients' average cost per day was $687 less while on
      the PCU than before transfer to PCU. Among patients who died in the hospital,
      average daily direct cost per patient in the days after transfer to PCU was $240
      lower as compared with patients being followed by PCCS on the general hospital
      wards (SE = $45, P < 0.001). CONCLUSION: Among patients who died in the hospital,
      transfer to a PCU is associated with significant cost savings as compared with
      patients on hospital wards who are seen by a PCCS.

PMID- 25847852
TI  - Physical and Psychological Distress Are Related to Dying Peacefully in Residents
      With Dementia in Long-Term Care Facilities.
AB  - CONTEXT: Although dying peacefully is considered an important outcome of high
      quality palliative care, large-scale quantitative research on dying peacefully
      and the factors associated with a peaceful death is lacking. OBJECTIVES: To gain
      insight into how many residents with dementia in long-term care facilities die
      peacefully, according to their relatives, and whether that assessment is
      correlated with observed physical and psychological distress. METHODS: This was a
      retrospective cross-sectional study of deceased nursing home residents in a
      representative sample of long-term care facilities in Flanders, Belgium (2010).
      Structured post-mortem questionnaires were completed by relatives of the
      resident, who were asked to what extent they agreed that the resident "appeared
      to be at peace" during the dying process. Spearman correlation coefficients gave
      the correlations between physical and psychological distress (as measured using
      the Symptom Management at the End of Life with Dementia and Comfort Assessment in
      Dying at the End of Life with Dementia scales) and dying peacefully (as measured
      using the Quality of Dying in Long Term Care instrument). RESULTS: The sample
      comprised 92 relatives of deceased residents with dementia. In 54% of cases,
      relatives indicated that the resident died peacefully. Weak-to-moderate
      correlations (0.2-0.57) were found between dying peacefully and physical distress
      in the last week of life. Regarding psychological distress, weak-to-moderate
      correlations were found for both the last week (0.33-0.44) and last month of life
      (0.28-0.47). CONCLUSION: Only half of the residents with dementia died peacefully
      as perceived by their relatives. Relatives' assessment of whether death was
      peaceful is related to both physical and psychological distress. Further
      qualitative research is recommended to gain more in-depth insights into the
      aspects on which relatives base their judgment of dying peacefully.

PMID- 25847854
TI  - Evaluation of competence-based teaching in higher education: From theory to
      practice.
AB  - Competence-based teaching in higher education institutions and its evaluation
      have become a prevalent topic especially in the European Union. However,
      evaluation instruments are often limited, for example to single student
      competencies or specific elements of the teaching process. The present paper
      provides a more comprehensive evaluation concept that contributes to sustainable
      improvement of competence-based teaching in higher education institutions. The
      evaluation concept considers competence research developments as well as the
      participatory evaluation approach. The evaluation concept consists of three
      stages. The first stage evaluates whether the competencies students are supposed
      to acquire within the curriculum (ideal situation) are well defined. The second
      stage evaluates the teaching process and the competencies students have actually
      acquired (real situation). The third stage evaluates concrete aspects of the
      teaching process. Additionally, an implementation strategy is introduced to
      support the transfer from the theoretical evaluation concept to practice. The
      evaluation concept and its implementation strategy are designed for internal
      evaluations in higher education and primarily address higher education
      institutions that have already developed and conducted a competence-based
      curriculum. 

PMID- 25847853
TI  - Microsurgical ear replantation-is venous repair necessary?-A systematic review.
AB  - BACKGROUND: A common postoperative observation after microsurgical ear
      replantation has been venous congestion necessitating alternate modes of
      decongestion, frequently in conjunction with blood transfusion. A comprehensive
      literature search was performed to assess the relationship between mode of
      vascular reconstruction and postoperative outcome as well as postoperative
      transfusion requirement after microsurgical ear replantation. METHODS: The search
      was limited to cases of microsurgical ear replantation following complete
      amputation. Only articles published in English and indexed in PubMed were
      included. RESULTS: The initial search retrieved 285 articles, which was narrowed
      down to 40 articles reporting on 60 cases that matched the aforementioned
      criteria. Reconstruction of the arterial and venous limb (Group 1) was performed
      in 63.3% of patients and artery-only anastomosis (Group 2) was performed in
      31.7%. Among measurable outcomes, only the duration of surgery was significantly
      different between groups (2.6 hours longer in Group 1 than Group 2; P = 0.0042).
      CONCLUSION: In light of contemporary data demonstrating successful artery-only
      ear replantation, replantation should not be abandoned when unable to establish
      venous outflow microsurgically. (c) 2015 Wiley Periodicals, Inc. Microsurgery
      36:345-350, 2016.

PMID- 25847855
TI  - Factors Affecting Indigenous West Australians' Health Behavior: Indigenous
      Perspectives.
AB  - The factors driving the disparity in health outcomes between Indigenous and non
      Indigenous Australians include socio-economic factors, racism, and history. The
      current study focused on exploring Indigenous participants' perspectives of the
      factors that affect the health behavior of their community members. Participatory
      action research methodology and a grounded theory approach were utilized. In
      total, 120 members of two urban West Australian Indigenous communities
      participated in focus group discussions. There was substantial similarity between
      the themes that emerged within the discussions held in the two communities.
      Factors relating to culture, social connections, racism, communication, and
      personal aspects were particularly salient to health behavior of the
      participants. Several of the themes including culture, racism, communication, and
      distrust highlight the tension caused by being a member of a minority cultural
      group that has been marginalized by the practices and attitudes of the dominant
      cultural group. Personal choice was sometimes prioritized over health. 

PMID- 25847856
TI  - Exploring the Hidden Barriers in Knowledge Translation: A Case Study Within an
      Academic Community.
AB  - Debates about knowledge translation (KT) typically focus on the research-practice
      gap, which appears to be premised on the assumption that academics are a
      homogeneous collective, sharing a common view. We argue that a number of hidden
      barriers need to be addressed related to the understanding, interpretation,
      ability, and commitment to translate knowledge within academic communities. We
      explore this by presenting a qualitative case study in a health sciences faculty.
      Applying organizational and management theory, we discuss different types of
      boundaries and the resultant barriers generated, ranging from diversity in
      understanding and perceptions of KT to varying motivations and incentives to
      engage in translational activity. We illustrate how we are using the empirical
      findings to inform the development of a KT strategy that targets the identified
      barriers. Investing in this internal KT-focused activity is an important step to
      maximize the potential of future collaborations between producers and users of
      research in health care. 

PMID- 25847857
TI  - Novel therapeutic approach for neurogenic erectile dysfunction: effect of
      neurotrophic tyrosine kinase receptor type 1 monoclonal antibody.
AB  - BACKGROUND: Erectile dysfunction (ED) is a major health issue in aged
      populations, and neurogenic ED is particularly difficult to treat. Novel
      therapeutic approaches are needed for treatment of neurogenic ED of peripheral
      origin. OBJECTIVE: To investigate the therapeutic effects of a neurotrophic
      tyrosine kinase receptor type 1 monoclonal antibody (TrkA-mAb) on erectile
      function and sexual behavior in a rat model of cavernous nerve injury (CNI).
      DESIGN, SETTING, AND PARTICIPANTS: In one experiment, 84 male rats were randomly
      assigned to seven groups. The groups underwent either CNI or sham surgery,
      subsequent injection into the major pelvic ganglion (IMPG) of phosphate-buffered
      saline (PBS), an immunoglobulin G (IgG) control, or TrkA-mAb, and then
      intracavernosal (IC) injection of either PBS or varying TrkA-mAb concentrations
      immediately after surgery and then 1 wk later. Erectile function was assessed and
      histologic/molecular analyses were performed at 6 wk after surgery. In a second
      experiment, 36 male rats were randomly divided into three groups. The groups
      underwent CNI or sham surgery and then IC injection of PBS, IgG, or TrkA-mAb
      immediately after surgery and for 5 wk thereafter. At 6 wk after surgery, the
      performance of the rats in sexual behavior tests was videotaped. INTERVENTION:
      CNI or sham surgery; IMPG of PBS, IgG, or TrkA-mAb; IC injection of PBS or TrkA
      mAb. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The intracavernous pressure
      response to cavernous nerve electrostimulation was measured and midpenile cross
      sections were histologically examined. Western blotting (WB) of cavernous tissue
      protein was performed. Rats were assessed for chasing, mounting, intromission,
      and ejaculation behaviors during sexual behavior tests. The data were analyzed
      using one-way analysis of variance followed by the Tukey-Kramer t test. RESULTS
      AND LIMITATIONS: Recovery of erectile function of varying degrees was observed in
      the TrkA-mAb groups. TrkA-mAb treatment significantly suppressed tyrosine
      hydroxylase-positive nerve fibers in the corpus cavernosum and enhanced neuronal
      nitric oxide synthase-positive fibers in the dorsal nerve. The ratio of smooth
      muscle to collagen in the corpus cavernosum was significantly improved in TrkA
      mAb treatment groups compared to PBS vehicle and IgG control groups. WB confirmed
      these biological changes. There was a nonsignificant increase in the average
      number of intromissions and ejaculations in the TrkA-mAb group. The study
      limitations include small sample size, variability in sexual behavior, lack of
      data on the neuromuscular mechanism involved, and lack of information of the role
      of neurotrophins or cytokines in regeneration. CONCLUSIONS: TrkA-mAb successfully
      inhibits sympathetic nerve regeneration, leads to parasympathetic nerve
      regeneration, and has therapeutic effects on ED and sexual behavior disorder in a
      rat model of CNI. PATIENT SUMMARY: This report provides strong evidence that a
      neurotrophic tyrosine kinase receptor type 1 monoclonal antibody (TrkA-mAb)
      inhibits sympathetic nerve regeneration, leads to parasympathetic nerve
      regeneration, and has therapeutic effects on erectile dysfunction and sexual
      behavior disorder in a rat model of cavernous nerve injury. The results raise the
      possibility that human patients with neurogenic erectile dysfunction may respond
      to TrkA-mAb in a manner that parallels the response seen in our rodent study.

PMID- 25847858
TI  - A review of the literature and proposed classification on e-prescribing:
      Functions, assimilation stages, benefits, concerns, and risks.
AB  - BACKGROUND: Evidence from the literature indicates that besides its benefits, e
      prescribing also generates new types of unintended medication errors that have
      the potential to harm patient safety. Analyzing both the benefits and risks of e
      prescribing can give health care organizations a better understanding of the
      improvements gained and errors generated by this technology. OBJECTIVES: To
      review the primary functions of e-prescribing and its assimilation stages in the
      health care context. This review also aims to classify the potential benefits,
      risks and concerns associated with e-prescribing along with factors contributing
      to e-prescribing errors. METHODS: A literature review was conducted primarily in
      Web of Sciences electronic databases. The online databases were searched for both
      peer-reviewed quantitative and qualitative research papers written in English and
      published between January 2008 and December 2014 (i.e., the last seven years).
      Several additional studies were also accessed through Google Scholar and the
      citations of the selected articles. A total of 73 publications met the study's
      inclusion criteria. RESULTS: The key benefits of e-prescribing were identified as
      improving the quality of health care services, increasing the efficiency and
      effectiveness of prescribing and dispensing medications, reducing medication
      errors, and health care cost savings. Failure to properly implement e-prescribing
      systems can also result in new types of errors that reduce workflow efficiency,
      increase medication cost, and threaten patient safety. In this study, factors
      contributing to potential errors were categorized into four primary groups
      (human, technical, interaction and organizational errors). CONCLUSIONS: This
      review identified the primary benefits and risks of e-prescribing services. The
      study contributes to the body of knowledge related to the design, adoption and
      use of e-prescribing by providing a clear reflection on its potential gains and
      risks. Based on the findings of this review, conducting research in several areas
      is quite promising as future work. This review also has practical implications
      for health care providers, e-prescribing software vendors and policy makers.

PMID- 25847859
TI  - Evaluation of natural radioactivity content in high-volume surface water samples
      along the northern coast of Oman Sea using portable high-resolution gamma-ray
      spectrometry.
AB  - Portable high-resolution gamma-ray spectrometry was carried out to determine the
      natural radioactivity levels in high volume surface water samples of the northern
      coast of Oman Sea, covering the coastal strip from Hormoz strait to Goatr
      seaport, for the first time. The water samples from 36 coastal and near shore
      locations were collected for analysis. Analyses on the samples collected were
      carried out to determine (226)Ra, (232)Th and (40)K contents. The concentration
      of (226)Ra, (232)Th and (40)K in surface water samples ranged between 2.19 and
      2.82 Bq/L, 1.66-2.17 Bq/L and 132.6-148.87 Bq/L, respectively. The activity
      profile of radionuclides shows low activity across the study area. The study also
      examined some radiation hazard indices. The external hazard index was found to be
      less than 1, indicating a low dose. The results of measurements will serve as
      background reference level for Oman Sea coastlines. 

PMID- 25847860
TI  - Influence of precipitation on (7)Be concentrations in air as measured by CTBTO
      global monitoring system.
AB  - Data collected by the International Monitoring System (IMS) during 2009-2012 were
      used to study influence of precipitation and relative humidity on changes in
      (7)Be concentrations in atmosphere. The significant decrease in (7)Be
      concentrations, corresponding to measurements collected by stations located
      within Intertropical Convergence Zone (ITCZ) is demonstrated. This effect can be
      attributed to the process of enhanced wet deposition within the ITCZ. To quantify
      this effect data collected by IMS stations within ITCZ were thoroughly analyzed.
      It was found that the atmospheric content of (7)Be strongly decreases under the
      rain conditions. The rain mediated depletion of (7)Be to half of its before rain
      value, needs about 62 h in case of light precipitation, while in the case of
      moderate precipitation about 38 h is needed. In addition the evaluated impact of
      humidity showed that increase in relative humidity by 20%, for example from 70%
      +/- 5% to 90% +/- 5% causes almost a double decrease in beryllium concentration
      in surface air. 

PMID- 25847861
TI  - Effects of active music therapy on the normal brain: fMRI based evidence.
AB  - The aim of this study was to investigate the neurophysiological bases of Active
      Music Therapy (AMT) and its effects on the normal brain. Twelve right-handed,
      healthy, non-musician volunteers were recruited. The subjects underwent 2 AMT
      sessions based on the free sonorous-music improvisation using rhythmic and
      melodic instruments. After these sessions, each subject underwent 2 fMRI scan
      acquisitions while listening to a Syntonic (SP) and an A-Syntonic (AP) Production
      from the AMT sessions. A 3 T Discovery MR750 scanner with a 16-channel phased
      array head coil was used, and the image analysis was performed with Brain Voyager
      QX 2.8. The listening to SP vs AP excerpts mainly activated: (1) the right middle
      temporal gyrus and right superior temporal sulcus, (2) the right middle frontal
      gyrus and in particular the right precentral gyrus, (3) the bilateral precuneus,
      (4) the left superior temporal sulcus and (5) the left middle temporal gyrus.
      These results are consistent with the psychological bases of the AMT approach and
      with the activation of brain areas involved in memory and autobiographical
      processes, and also in personal or interpersonal significant experiences. Further
      studies are required to confirm these findings and to explain possible effects of
      AMT in clinical settings.

PMID- 25847862
TI  - Curcumin induces the apoptosis of non-small cell lung cancer cells through a
      calcium signaling pathway.
AB  - Curcumin is known for its anti-proliferative effects in lung cancer cells.
      Studies have demonstrated that an increase in the levels of intracellular free
      calcium ([Ca2+]i) is involved in curcumin-induced apoptosis. In this study, we
      aimed to investigate the involvement of calcium overload in the anti
      proliferative effects of curcumin on lung cancer cells and the possible
      mechanisms involved. A549 and H1299 lung cancer cells were incubated with serial
      diluted curcumin. MTT assay was used to assess the cytotoxic effects of curcumin
      on the lung cancer cells; the inositol 1,4,5-trisphosphate receptor (IP3R, a key
      regulator of [Ca2+]i signaling) was blocked by its specific inhibitor,
      xestospongin C (XSC). Hoechst 33342, Fura-2/AM and rhodamine 123 fluorescence
      staining was employed to detect the apoptosis, the [Ca2+]i level and
      mitochondrial potential in the lung cancer cells. The expression levels of B-cell
      lymphoma-2 (Bcl-2), cleaved caspase-3 and cleaved caspase-9, and the
      phosphorylation level of IP3R were evaluated by western blot analysis. Our
      results revealed that curcumin inhibited cell growth, increased the [Ca2+]i level
      and increased the apoptosis of the lung cancer cells in a concentration-dependent
      manner. However, XSC attenuated the increase in the [Ca2+]i level and apoptosis,
      and also reversed the curcumin-induced loss of mitochondrial potential potential.
      Treatment with curcumin downregulated the expression of Bcl-2, and elevated the
      phosphorylation level of IP3R in a concentration-dependent manner. However, this
      effect was not reversed by treatment with XSC. In conclusion, the cytotoxic
      effects of curcumin on lung cancer cells were induced by calcium overload, which
      involves Bcl-2 mediated IP3R phosphorylation.

PMID- 25847863
TI  - Construction of helical coordination polymers via flexible conformers of bis(3
      pyridyl)cyclotetramethylenesilane: metal(ii) and halogen effects on luminescence,
      thermolysis and catalysis.
AB  - Infinite rectangular-tubular helices, [MX2L] (M = Zn(ii), Hg(ii); X(-) = Cl(-),
      Br(-); L = bis(3-pyridyl)cyclotetramethylenesilane), have been efficiently
      constructed via the combined effects of the potential flexible conformers of L
      and the tetrahedral geometry of M(ii) ions. This helical molecular system affords
      a racemic mixture of P- and M-helices in a crystal. The helical pitches
      (7.8934(4)-8.1560(2) A) that are sensitive to the nature of M(ii) ions and halide
      anions are attributable to subtle change in the flexible dihedral angles between
      the two pyridyl groups around Si and the M(ii) hinges. Their photoluminescence
      intensities, correspondingly, are in the order [ZnCl2L] > [ZnBr2L] ? [HgCl2L] >
      [HgBr2L]. Zinc(ii) complexes show recyclable catalytic effects on the
      transesterification reaction in the order [ZnCl2L] > [ZnBr2L]. Calcination of
      [ZnCl2L] and [ZnBr2L] at 500  degrees C produces uniform hexagonal tubular spire
      crystals of 1.2 * 1.2 * 4.0 MUm(3) dimensions and spheres, respectively. 

PMID- 25847864
TI  - Graphene-encapsulated silica as matrix solid-phase dispersion extraction sorbents
      for the analysis of poly-methoxylated flavonoids in the leaves of Murraya
      panaculata (L.) Jack.
AB  - In this study, graphene-encapsulated silica was synthesized by a hydrothermal
      reduction strategy. The presence of silica in graphene was identified by Fourier
      transform infrared spectrometry, X-ray diffraction and scanning electron
      microscopy. The graphene-encapsulated silica subsequently was used as adsorbent
      for matrix solid-phase dispersion extraction of poly-methoxylated flavonoids from
      the dried leaves of Murraya panaculata (L.) Jack. Compared with the other
      adsorbents (graphene, silica gel, C18 silica, neutral alumina, diatomaceous
      earth) and without any adsorbents, better results were obtained. Then a method
      for analysis of poly-methoxylated flavonoids was established by coupling matrix
      solid-phase dispersion extraction with ultra high performance liquid
      chromatography and UV detection. Compared with reflux extraction and ultrasonic
      extraction, the proposed method is quicker, more efficient and more environmental
      protection. Less than 10 min is needed from extraction to detection. 

PMID- 25847865
TI  - Diversity and Phylogeny of Gymnodiniales (Dinophyceae) from the NW Mediterranean
      Sea Revealed by a Morphological and Molecular Approach.
AB  - The diversity and phylogeny of dinoflagellates belonging to the Gymnodiniales
      were studied during a 3-year period at several coastal stations along the Catalan
      coast (NW Mediterranean) by combining analyses of their morphological features
      with rDNA sequencing. This approach resulted in the detection of 59 different
      morphospecies, 13 of which were observed for the first time in the Mediterranean
      Sea. Fifteen of the detected species were HAB producers; four represented novel
      detections on the Catalan coast and two in the Mediterranean Sea. Partial rDNA
      sequences were obtained for 50 different morphospecies, including novel LSU rDNA
      sequences for 27 species, highlighting the current scarcity of molecular
      information for this group of dinoflagellates. The combination of morphology and
      genetics allowed the first determinations of the phylogenetic position of several
      genera, i.e., Torodinium and many Gyrodinium and Warnowiacean species. The
      results also suggested that among the specimens belonging to the genera
      Gymnodinium, Apicoporus, and Cochlodinium were those representing as yet
      undescribed species. Furthermore, the phylogenetic data suggested taxonomic
      incongruences for some species, i.e., Gyrodinium undulans and Gymnodinium
      agaricoides. Although a species complex related to G. spirale was detected, the
      partial LSU rDNA sequences lacked sufficient resolution to discriminate between
      various other Gyrodinium morphospecies. 

PMID- 25847866
TI  - Different utilization of alginate and other algal polysaccharides by marine
      Alteromonas macleodii ecotypes.
AB  - The marine bacterium Alteromonas macleodii is a copiotrophic r-strategist, but
      little is known about its potential to degrade polysaccharides. Here, we studied
      the degradation of alginate and other algal polysaccharides by A. macleodii
      strain 83-1 in comparison to other A. macleodii strains. Cell densities of strain
      83-1 with alginate as sole carbon source were comparable to those with glucose,
      but the exponential phase was delayed. The genome of 83-1 was found to harbour an
      alginolytic system comprising five alginate lyases, whose expression was induced
      by alginate. The alginolytic system contains additional CAZymes, including two
      TonB-dependent receptors, and is part of a 24 kb genomic island unique to the A.
      macleodii 'surface clade' ecotype. In contrast, strains of the 'deep clade'
      ecotype contain only a single alginate lyase in a separate 7 kb island. This
      difference was reflected in an eightfold greater efficiency of surface clade
      strains to grow on alginate. Strain 83-1 furthermore hydrolysed laminarin,
      pullulan and xylan, and corresponding polysaccharide utilization loci were
      detected in the genome. Alteromonas macleodii alginate lyases were predominantly
      detected in Atlantic Ocean metagenomes. The demonstrated hydrolytic capacities
      are likely of ecological relevance and represent another level of adaptation
      among A. macleodii ecotypes.

PMID- 25847867
TI  - Effect of hyperbaric oxygen therapy on amphotericin-B induced acute renal failure
      in rats.
AB  - AIM: Acute renal injury may occur after amphotericin B (AmB) administration. The
      hypothesized injury mechanism is renal vasoconstriction and direct toxic damage.
      Hyperbaric oxygen therapy (HBO) is indicated for treatment of many ischemic
      events but not for acute renal failure (ARF). The aim of this study was to
      investigate the role of HBO therapy in AmB induced ARF. METHODS: ARF was induced
      in 41 Sprague-Dawley rats by a single dose of 75 mg/kg AmB. The rats were
      randomly divided into two groups; one group was treated with daily HBO for 3
      consecutive days. The control group received no HBO treatment. Parameters of
      renal function were taken on the 5th day after AmB administration. RESULTS: Forty
      one rats were treated with AmB, 21 received HBO and 20 served as controls. Body
      weight loss following the administration of AmB was 13.5+14.7% in the HBO treated
      rats, as opposed to 24.6+5% in the control group (P=0.004). Serum creatinine and
      urea were 0.49+0.13 mg/dL and 200.63+87.82 mg/dL in the treatment group and
      0.70+0.22 mg/dL and 368.01+169.35 mg/dL, respectively in the control (P=0.001).
      CONCLUSION: In this model of AmB-induced ARF, HBO treatment alleviated renal
      injury as reflected by changes in serum creatinine and urea levels.

PMID- 25847868
TI  - Continuous intravenous infusion of furosemide is more effective and safer than
      coadministration of albumin and furosemide in patients with nephrotic syndrome.

PMID- 25847869
TI  - The early recovery of continence after retropubic radical prostatectomy is
      possible: preservation of the smooth muscular internal (vescical) sphincter and
      of the proximal urethra.

PMID- 25847870
TI  - The cytosol must flow: intercellular transport through plasmodesmata.
AB  - Plant cells are connected across cell walls by nanoscopic channels called
      plasmodesmata (PD), which allow plant cells to share resources and exchange
      signaling molecules. Several protein components of PD membranes have been
      identified, and recent advances in superresolution live-cell microscopy are
      illuminating PD ultrastructure. Restricting transport through PD is crucial for
      morphogenesis, since hormones and hundreds of transcription factors regularly
      move through PD, and this transport must stop to allow cells to begin
      differentiating. Chloroplasts and mitochondria regulate PD function through
      signal transduction networks that coordinate plant physiology and development.
      Recent discoveries on the relationships of land plants and their algal relatives
      suggest that PD have evolved independently in several lineages, emphasizing the
      importance of cytosolic bridges in multicellular biology. 

PMID- 25847871
TI  - In regard to "Risk of second non-breast cancer after radiotherapy for breast
      cancer: A systematic review and meta-analysis of 762,468 patients".

PMID- 25847872
TI  - Genome-wide comparative analysis of digital gene expression tag profiles during
      maize ear development.
AB  - The present study profiled and analyzed gene expression of the maize ear at four
      key developmental stages. Based on genome-wide profile analysis, we detected
      differential mRNA of maize genes. Some of the differentially expressed genes
      (DEGs) were predicted to be potential candidates of maize ear development.
      Several well-known genes were found with reported mutant analyses, such as,
      compact plant2 (ct2), zea AGAMOUS homolog1 (zag1), bearded ear (bde), and silky1
      (si1). MicroRNAs such as microRNA156 were predicted to target genes involved in
      maize ear development. Antisense transcripts were widespread throughout all the
      four stages, and are suspected to play important roles in maize ear development.
      Thus, identification and characterization of important genes and regulators at
      all the four developmental stages will contribute to an improved understanding of
      the molecular mechanisms responsible for maize ear development. 

PMID- 25847873
TI  - Structural and evolutionary divergence of cyclic nucleotide binding domains in
      eukaryotic pathogens: Implications for drug design.
AB  - Many cellular functions in eukaryotic pathogens are mediated by the cyclic
      nucleotide binding (CNB) domain, which senses second messengers such as cyclic
      AMP and cyclic GMP. Although CNB domain-containing proteins have been identified
      in many pathogenic organisms, an incomplete understanding of how CNB domains in
      pathogens differ from other eukaryotic hosts has hindered the development of
      selective inhibitors for CNB domains associated with infectious diseases. Here,
      we identify and classify CNB domain-containing proteins in eukaryotic genomes to
      understand the evolutionary basis for CNB domain functional divergence in
      pathogens. We identify 359 CNB domain-containing proteins in 31 pathogenic
      organisms and classify them into distinct subfamilies based on sequence
      similarity within the CNB domain as well as functional domains associated with
      the CNB domain. Our study reveals novel subfamilies with pathogen-specific
      variations in the phosphate-binding cassette. Analyzing these variations in light
      of existing structural and functional data provides new insights into ligand
      specificity and promiscuity and clues for drug design. This article is part of a
      Special Issue entitled: Inhibitors of Protein Kinases. 

PMID- 25847874
TI  - Analysis on the expression and function of syndecan in the Pacific white shrimp
      Litopenaeus vannamei.
AB  - Syndecan is considered to be a multifunctional protein which functions as a cell
      surface receptor involved in cell adhesion, migration, cytoskeleton organization
      and differentiation. Previous bioinformatic analysis has revealed that syndecan
      in shrimp might interact with white spot syndrome virus (WSSV). In the present
      study, we experimentally studied the function of syndecan in shrimp immunity. The
      syndecan from Litopenaeus vannamei (LvSDC) was cloned and analyzed. The full
      length cDNA of LvSDC was 1005 bp, consisting of 59 bp 5'-UTR, 253 bp 3'-UTR, and
      693 bp open reading frame encoding 230 amino acids. LvSDC consisted of an
      extracellular domain (ED), a transmembrane domain (TM) and a cytoplasmic domain
      (CD). TM and CD shared high similarities with those of syndecan proteins from
      other species. LvSDC was ubiquitously expressed in all tested tissues, with the
      highest level in Oka. After WSSV challenge, the transcription level of LvSDC in
      Oka was apparently up-regulated. Recombinant LvSDC protein and its rabbit
      polyclonal antibody were prepared for detecting the location of LvSDC in
      hemocytes using immunocytochemistry approach. Data showed that LvSDC mainly
      located at the cell membrane and the cytoplasm of hemocytes. After silencing of
      LvSDC with siRNA, the WSSV copy numbers and mortality of shrimp after WSSV
      infection were both significantly decreased. These data provide useful
      information for understanding the immune mechanism of shrimp to WSSV infection. 

PMID- 25847875
TI  - Identification and functional characterization of grass carp IL-17A/F1: An
      evaluation of the immunoregulatory role of teleost IL-17A/F1.
AB  - In mammals, IL-17A and IL-17F are hallmark cytokines of Th17 cells which act
      significant roles in eradicating extracellular pathogens. IL-17A and IL-17F
      homologs nominated as IL-17A/F1-3 have been revealed in fish and their functions
      remain largely undefined. Here we identified and characterized grass carp IL
      17A/F1 (gcIL-17A/F1) in fish immune system. In this regard, both tissue
      distribution and inductive expression of gcIL-17A/F1 indicated its possible
      involvement in immune response. Moreover, recombinant gcIL-17A/F1 (rgcIL-17A/F1)
      was prepared and displayed an ability to enhance pro-inflammatory cytokines (IL
      1beta, TNF-alpha and IL-6) mRNA expression in head kidney leukocytes. It is
      suggestive of that gcIL-17A/F1 may act as a proinflammatory cytokine in fish
      immunity. Besides, rgcIL-17A/F1 induced gene expression and protein release of
      grass carp chemokine CXCL-8 (gcCXCL-8) in head kidney cells (HKCs), probably via
      NF-kappaB, p38 and Erk1/2 pathways. In particular, culture medium from the HKCs
      treated by rgcIL-17A/F1 could stimulate peripheral blood leukocytes migration and
      immunoneutralization of endogenous gcCXCL-8 could partially attenuate this
      stimulation, suggesting that rgcIL-17A/F1 could recruit immune cells through
      producing gcCXCL-8 as mammalian IL-17 A and F. Taken together, we not only
      identified the pro-inflammatory role of gcIL-17A/F1 in host defense, but also
      provided the basis for clarifying Th17 cells in teleost. 

PMID- 25847877
TI  - Noninvasive investigation of exocrine pancreatic function: Feasibility of cine
      dynamic MRCP with a spatially selective inversion-recovery pulse.
AB  - PURPOSE: To investigate the feasibility of noncontrast-enhanced cine dynamic
      magnetic resonance cholangiopancreatography (MRCP) with a spatially selective
      inversion-recovery (IR) pulse for evaluating exocrine pancreatic function in
      comparison with the N-benzoyl-L-tyrosyl-p-aminobenzoic acid (BT-PABA) test as a
      pancreatic exocrine function test. MATERIALS AND METHODS: Twenty subjects with or
      without chronic pancreatitis were included. MRCP with a spatially selective IR
      pulse was repeated every 15 seconds for 5 minutes to acquire a total of 20 images
      (cine-dynamic MRCP). The median and mean frequency of the observation (the number
      of times) and the moving distance (mean secretion grading scores) of pancreatic
      juice inflow on cine-dynamic MRCP were compared with a BT-PABA test. RESULTS: The
      urinary PABA excretion rate (%) had significant positive correlations with both
      the mean secretion grade (r = 0.66, P = 0.002) and frequency of secretory inflow
      (r = 0.62, P = 0.004) in cine dynamic MRCP. Both the mean frequency of
      observations of pancreatic secretory inflow (1.4 +/- 1.6 times vs. 14.3 +/- 4.2
      times, P < 0.001) and the mean secretion grade (grade = 0.16 +/- 0.24 vs. grade =
      1.81 +/- 0.81, P < 0.001) was significantly lower in the chronic pancreatitis
      group than in the normal subject group. CONCLUSION: Cine dynamic MRCP with a
      spatially selective IR pulse may have potential for estimating the pancreatic
      exocrine function noninvasively as a substitute for the BT-PABA test.

PMID- 25847876
TI  - MicroRNA hsa-miR-4717-5p regulates RGS2 and may be a risk factor for anxiety
      related traits.
AB  - Regulator of G-protein Signaling 2 (RGS2) is a key regulator of G-protein-coupled
      signaling pathways involved in fear and anxiety. Data from rodent models and
      genetic analysis of anxiety-related traits and disorders in humans suggest down
      regulation of RGS2 expression to be a risk factor for anxiety. Here we
      investigated, whether genetic variation in microRNAs mediating
      posttranscriptional down-regulation of RGS2 may be a risk factor for anxiety as
      well. 75 microRNAs predicted to regulate RGS2 were identified by four
      bioinformatic algorithms and validated experimentally by luciferase reporter gene
      assays. Specificity was confirmed for six microRNAs (hsa-miR-1271-5p, hsa-miR-22
      3p, hsa-miR-3591-3p, hsa-miR-377-3p, hsa-miR-4717-5p, hsa-miR-96-5p) by
      disrupting their seed sequence at the 3' untranslated region of RGS2. Hsa-miR
      4717-5p showed the most robust effect on RGS2 and regulated two other candidate
      genes of anxiety disorders (CNR1 and IKBKE) as well. Two SNPs (rs150925,
      rs161427) within and 1,000 bp upstream of the hostgene of hsa-miR-4717-5p
      (MIR4717) show a minor allele frequency greater than 0.05. Both were in high
      linkage disequilibrium (r(2) = 1, D' = 1) and both major (G) alleles showed a
      trend for association with panic disorder with comorbid agoraphobia in one of two
      patient/control samples (combined n(patients) = 497). Dimensional anxiety traits,
      as described by Anxiety Sensitivity Index (ASI) and Agoraphobic Cognitions
      Questionnaire (ACQ) were significantly higher among carriers of both major (G)
      alleles in a combined patient/control sample (n(combined) = 831). Taken together,
      data indicate that MIR4717 regulates human RGS2 and contributes to the genetic
      risk towards anxiety-related traits.

PMID- 25847878
TI  - [Which health systems are capable to fight Ebola and other emergencies in Sub
      Saharan Africa].

PMID- 25847879
TI  - [AIDS research in the South].

PMID- 25847880
TI  - [Evaluation of a new polyvalent antivenom against snakebite envenomation
      (Inoserp(r) Panafricain) in two different epidemiological settings: Northern
      Benin and Maritime Guinea].
AB  - OBJECTIVES: The authors evaluated the safety and efficacy of Inoserp((r)) Pan
      Africa, a new polyvalent antivenom composed of highly purified and lyophilized
      fragments of F(ab')2 immunoglobulins, recently registered in Benin and Guinea.
      METHODS: We treated 100 patients in northern Benin (Atacora) and 109 in Maritime
      Guinea (Kindia) with confirmed envenomation. Treatment consisted of intravenous
      administration of 1 vial for uncomplicated envenomation, and 2 vials for
      hemorrhagic or neurotoxic envenomation. The dose was repeated when bleeding or
      signs of neurotoxicity persisted or appeared. RESULTS: In Atacora, on arrival at
      the hospital, 90% of patients had incoagulable blood, and 50% were bleeding. The
      resolution of these bleeding disorders was obtained in less than 3 hours for 50%
      of the patients and in less than 24 hours for 98%. Four patients died. In Kindia,
      96 patients (88%) presented viper bites with pain + edema and 13 (12 %) others
      showed elapid (ptosis, dyspnea) envenomation. One patient bitten by a member of
      the Elapidae family, died despite early treatment. In Benin, protocol deviations
      for 60% of patients led to significant underdosing of the antivenom; the
      proportion was much lower (2%) in Guinea. Signs of intolerance after Inoserp((r))
      Pan Africa administration were reported in 8% of patients. All these symptoms
      were mild and disappeared rapidly after an antihistamine or corticosteroid
      treatment. CONCLUSION: Treatment using intravenous Inoserp((r)) Pan Africa
      appeared to be well tolerated and effective against snakebite envenomation in
      both epidemiological settings.

PMID- 25847882
TI  - [Children hospitalized with severe malaria in Kinshasa (Democratic Republic of
      the Congo): Household characteristics and factors associated with mortality].
AB  - BACKGROUND: Malaria is a major health problem in tropical Africa. In DRC, little
      is known about the characteristics of households of children with severe malaria
      or the factors associated with its lethality, especially relative to hospital
      status. METHODS: This study of 9 hospitals of the city-province of Kinshasa
      studied 1350 children younger than 15 years and hospitalized for severe malaria
      from January to November 2011. RESULTS: More than three quarters of children
      admitted to public (state) and church hospitals were from poor households and
      with uneducated mothers (P < 0.001). The case-fatality rate (5.9% of all
      children) differed according to hospital status: 5.3% in state hospitals, 8.4% in
      private hospitals, and 4.0% in the faith-based hospitals (P < 0.001). The risk of
      death was significantly associated with circulatory collapse (odds ratio, OR =
      10.3), number of associated syndromes >2 (OR = 3.5), z-score of weight-for-age <=
      2 (OR = 3.5), delay in seeking medical care (OR = 4.9), body temperature >=40
      degrees C (OR = 2.9), respiratory distress (OR = 1.9) and home rental (versus
      ownership) a tenant (OR = 2.8), and anorexia was a protective factor (odds ratio
      = 0.5). CONCLUSION: Severe cases of malaria are rife in poor households and
      periurban residential areas. Orienting prevention, control, and care- according
      to the vulnerability of affected households and providing early treatment are
      imperative if we are to reduce mortality from malaria.

PMID- 25847881
TI  - [The impact of urbanization on malaria infection rate and parasite density in
      children in the municipality of Yopougon, Abidjan (Cote d'Ivoire)].
AB  - From September 23-30, 2005, we conducted a cross-sectional study in six townships
      of Yopougon, a municipality of Abidjan. These townships were grouped in three
      levels of urbanization (village, precarious township, and residential township).
      The main objective of this survey was to determine the impact of urbanization on
      the malaria infection (parasite) rate and parasite density, and their
      consequences on the heterogeneity of malaria transmission in urban Abidjan.
      Specifically we compared these rates in all three urbanization levels, selecting
      two townships for each level to take environmental specificities observed from
      previous data into account. The study included 400 households per township. All
      children younger than 5 years in these households were included. Thick and thin
      blood smears were taken for each child on slides, and each slide was examined by
      microscope after staining. The malaria infection rate was 21.8%, indicating
      mesoendemic malaria. Its distribution varied significantly between the three
      urbanization levels. Malaria parasite densities also varied significantly between
      them. These results confirm the involvement of urbanization in the heterogeneity
      of malaria transmission in the city of Abidjan. 

PMID- 25847883
TI  - [88 years of cutaneous leishmaniasis in Morocco].
AB  - Leishmaniasis in its cutaneous form is a public health problem in Morocco. The
      objectives of this study were to assess the development of its epidemiological
      profile, identify the relevant species, and determine the location of the
      identified cases and their distribution by year, by sex, and by age. This
      retrospective epidemiological study covers a period of 88 years and concerns all
      reported cases of cutaneous leishmaniasis (CL) in Morocco from the first
      description in 1922 until 2010. During this period, 56,194 cases have been
      reported; they account for 95.7% of all cases of leishmaniasis (n = 58,710). The
      endemicity of CL has changed over time. The increase in its incidence is likely
      to be explained both by improved reporting and by a real increase in the number
      of cases. 

PMID- 25847884
TI  - Comparisons of the results of peripheral nerve defect repair with fibrin conduit
      and autologous nerve graft: An experimental study in rats.
AB  - INTRODUCTION: The standard treatment for nerve defects is nerve autograft. There
      is no conduit available that provides the same regenerative capacity of nerve
      autograft. This study evaluated the histological and functional recovery of nerve
      defects treated with fibrin conduit in comparison to the nerve autograft, in a
      rat model. METHOD: A sciatic nerve injury model (10-mm defect) was performed in
      20 Wistar rats, nerve defect was reconstructed using a fibrin conduit (n = 10). A
      nerve autograft was used as control (n = 10). The walking behavior was measured
      by footprint analysis at 4, 8, and 12 weeks and sciatic function index was
      determined. After 12 weeks, histological analysis was performed to evaluate the
      regenerated nerve and measured axonal density. The triceps surae muscle weight
      was also evaluated. RESULTS: The fibrin conduit group showed less improvement in
      walking behavior compared to nerve autograft (-53 +/- 2 vs. -36 +/- 2; P < 0.001
      at 12 weeks). The fibrin conduit group presented axonal density of 40.0
      axons/10.995MUm2 and the nerve autograft group had 67.2 axons/10.995MUm2 (P <
      0.001). The triceps surae muscle weight ratio of the fibrin conduit group was 41
      +/- 3% versus 71 +/- 4% of the nerve autograft group (P < 0.001). CONCLUSION: The
      fibrin conduit could be used for nerve reconstruction following peripheral nerve
      injury in the rat model. However, the functional recovery in the fibrin conduit
      repair group was worse than that in nerve autograft group and the nerve repair
      with the fibrin conduit has less myelinated fibers when compared to the repair
      with nerve autograft.

PMID- 25847886
TI  - How life history influences the responses of the clam Scrobicularia plana to the
      combined impacts of carbamazepine and pH decrease.
AB  - In the present study, the bivalve Scrobicularia plana, collected from two
      contrasting areas (pristine location and mercury contaminated area), was selected
      to assess the biochemical alterations imposed by pH decrease, carbamazepine (an
      antiepileptic) and the combined effect of both stressors. The effects on
      oxidative stress related biomarkers after 96 h exposure revealed that pH decrease
      and carbamazepine induced alterations on clams, with greater impacts on
      individuals from the contaminated area which presented higher mortality, higher
      lipid peroxidation and higher glutathione S-transferase activity. These results
      emphasize the risk of extrapolating results from one area to another, since the
      same species inhabiting different areas may be affected differently when exposed
      to the same stressors. Furthermore, the results obtained showed that, when
      combined, the impact of pH decrease and carbamazepine was lower than each
      stressor acting alone, which could be related to the defence mechanism of valves
      closure when bivalves are under higher stressful conditions. 

PMID- 25847887
TI  - Venous leakage treatment revisited: pelvic venoablation using aethoxysclerol
      under air block technique and Valsalva maneuver.
AB  - OBJECTIVE: We evaluated the effectiveness of pelvic vein embolization with
      aethoxysclerol in aero-block technique for the treatment of impotence due to
      venous leakage in men using sildenafil for intercourse. The aim of the procedure
      was to reduce the use of sildenafil. METHODS: A total of 96 patients with veno
      occlusive dysfunction, severe enough for the need of PDE5 inhibitors for vaginal
      penetration, underwent pelvic venoablation with aethoxysclerol. The mean patient
      age was 53.5 years. Venous leaks were identified by Color Doppler Ultrasound
      after intracavernous alprostadil injection. Under local anesthesia a 20-gauge
      needle was inserted into the deep dorsal penile vein. The pelvic venogram was
      obtained through deep dorsal venography. Aethoxysclerol 3% as sclerosing agent
      was injected after air-block under Valsalva manoeuver. Success was defined as the
      ability to achieve vaginal insertion without the aid of any drugs, vasoactive
      injections, penile prosthesis, or vacuum device. Additionally, a pre- and post-
      therapy IIEF score and a digital overnight spontaneous erections protocol (OSEP)
      with the NEVATM-system was performed. RESULTS: At 3 month follow-up 77 out of 96
      patients (80.21%) reported to have erections sufficient for vaginal insertion
      without the use of any drug or additional device. Four (4.17%) patients did not
      report any improvement. Follow up with color Doppler ultrasound revealed a new or
      persistent venous leakage in 8 (8.33%) of the patients. No serious complications
      occurred. CONCLUSIONS: Our new pelvic venoablation technique using aethoxysclerol
      in air-block technique was effective, minimally invasive, and cost-effective. All
      patients were able to perform sexual intercourse without the previously used
      dosage of PDE5 inhibitor. This new method may help in patients with contra
      indications against PDE5 inhibitors, in patients who cannot afford the frequent
      usage of expensive oral medication or those who do not fully respond to PDE5
      inhibitors.

PMID- 25847888
TI  - Tubular ectasia of the rete testis (TERT). Differential diagnosis of cystic
      testicular disorders.
AB  - The ultrasound scan plays an essential role in the urological-andrological
      diagnosis. High-resolution transducers (8-15 MHz) make it possible to prove
      increasingly small changes. The assessment of cystic masses in the testis can
      also be difficult for experienced doctors. However, a precise diagnosis is
      crucial for the patient to avoid further invasive diagnostics and therapy. The
      differential diagnosis of benign intra-testicular cystic lesions include the
      tubular ectasia of the rete testis (TERT), the cystic dysplasia, epidermoid
      cysts, dermoid cysts, simple testicular cysts and cysts of the tunica albuginea.
      Malign testicular tumours with cystic changes are particularly the mature
      teratoma, carcinomas of the epididymis and metastasis. The following overview
      shows different sonographic images and interpretations with a particular focus on
      TERT. 

PMID- 25847889
TI  - Sexual dysfunctions after transurethral resection of the prostate (TURP):
      evidence from a retrospective study on 264 patients.
AB  - OBJECTIVES: Benign prostatic hyperplasia (BPH) and sexual dysfunctions are
      diseases with a high prevalence in aged men. Several studies have found a link
      between BPH and LUTS resulting from deterioration in sexual function in men aged
      50 years and older for whom TURP is considered the gold standard. The impact of
      TURP on sexual functions still remain uncertain, nor is it clear what
      pathophysiological mechanism underlying the emergence of new episodes of Erectile
      Dysfunction (ED) following TURP in patients with normal sexual function before
      surgery, while retrograde ejaculation and ejaculate volume reduction represent a
      clear side effect; derived from BPH treatment. The aim of this study was to
      retrospectively evaluate the effects of transurethral resection of the prostate
      (TURP) on sexual function in patients operated in the period 2008-2012 at the
      Department of Urology of the University Hospital P. Giaccone, and at Villa Sofia
      Cervello Hospital- Palermo. Secondary objective was to reconnect the sample data
      to interventional practice and international standards. MATERIALS AND METHODS:
      The retrospective longitudinal study was conducted on 264 of the 287 recruitable
      patients, aged between 50 and 85 years, suffering from BPH who underwent to TURP
      in the period 2008-2012. Telephone interviews were conducted and the
      International Index of Erectile Function (IIEF) was administered to assess sexual
      function. Patients enrolled were asked to respond to the test by referring at
      first to their sexual status in the period before surgery and subsequently to the
      state of their sexual function after treatment so as to obtain, for each patient,
      a pre- and post-TURP questionnaire in order to get comparisons that corresponding
      to reality and to avoid overestimation of the dysfunctional phenomenon. RESULTS:
      In the pre-TURP, the 94.32% of the sample reported being sexually active, with
      good erectile function in 41.3% of cases, ED mild/moderate in 51.5% and complete
      ED in 1, 5% of cases; good libido in 62.9% of cases, lack of libido in 31.4% of
      cases and absent in 5.7% of cases (the latter data corresponded to patients not
      sexually active); to be sexually satisfied in 29.5% of cases, slightly
      dissatisfied in 11, 7% of cases, moderately in 35.3% of cases, dissatisfied and
      very dissatisfied in 23.5% of cases (of which 17.8% sexually active and 5.7% non
      active). In the post-TURP 89.4% of the sample reported being sexually active,
      with good erectile function in 39.1% of cases, DE mild/moderate in 46.9% and
      complete DE in 4% of cases; good libido in 53.8% of cases, lack of libido in
      33.7% of cases and absent in 13.5% of cases (including 1.9% of sexually active
      and 10.6% of non-active); to be sexually satisfied in 29.5% of cases, slightly
      dissatisfied in 9.5% of cases, moderately in 35.3% of cases, dissatisfied and
      very dissatisfied in 17.8% of cases (of which 14.8% sexually active and 10.6%
      inactive). Retrograde ejaculation was referred in 47.8% of those sexually active
      after TURP (42.8% if we consider the whole sample). CONCLUSIONS: TURP had no
      negative impact on erectile function in contrast to ejaculatory function. Of the
      109 patients with good erectile function in pre-TURP, 5.8% reported a worsening
      of erectile function after TURP. Among the 136 patients with ED moderate/mild pre
      TURP 3.7% reported a worsening in the post-TURP, 16.2% reported an improvement,
      while 9.5% stopped any sexual activity. In 3.7% of the cases a complete ED was
      reported after TURP, while a decline of libido and sexual satisfaction was
      detected in all patients with worsening of sexual function. Retrograde
      ejaculation was observed in 48% of those sexually active after TURP. Particular
      attention has to be paid to the psychological aspects, both before surgery and in
      the postoperative period, which may become an important factor in the decline of
      sexual activity.

PMID- 25847890
TI  - Light-emitting diode exposure enhances sperm motility in men with and without
      asthenospermia: preliminary results.
AB  - OBJECTIVE: To evaluate the effect of light-emitting diode (LED) on sperm motility
      in men with and without asthenospermia. MATERIAL AND METHODS: Semen samples from
      27 men were assessed and washed. An aliquot was taken from each sample as a
      control. The remaining amount was exposed to red LED for 2, 5 and 10 minutes.
      Sperm motility from the test and control tubes were re-checked at the end of each
      time interval. In 11 of these 27 samples, the same protocol was repeated without
      sperm washing. Evaluation of sperm creatine kinase (CK) activity, hypoosmotic
      swelling (HOS) test and aniline blue staining (ANBS) were undertaken after
      phototherapy in additional 15 samples. RESULTS: Progressive sperm motility
      increased significantly after LED treatment at the different time intervals
      whether in washed (p = 0.000) or non-washed (p = 0.003) samples. The amount of
      the increase in motility in washed aliquots was significantly more (p = 0.000)
      than in naive semen. Sperm CK activity increased, but was not significant whilst
      there were no changes regarding HOS and ANBS. CONCLUSION: Red LED is a promising
      safe tool to boost sperm motility in vitro. This may have a great implication on
      maximizing the possibilities and outcomes of intrauterine insemination trials.

PMID- 25847891
TI  - Smoking, diabetes, blood hypertension: possible etiologic role for Peyronie's
      disease? Analysis in 279 patients with a control group in Sicily.
AB  - OBJECTIVE: To assess the proportion of patients with Peyronie's Disease (PD) and
      the possible association with its potential risk factors in the general
      population of the central and western Sicily in our weekly andrological
      outpatient clinic. MATERIALS AND METHODS: We recruited a sample of 279
      consecutive patients consulting our andrological outpatient clinic. Two arms were
      created: the first one composed by PD patients (men with symptoms suggestive for
      PD), the second one composed by patients with other andrological diseases
      (control arm). For each patient we evaluated the age, cigarette smoking,
      diabetes, blood hypertension and erectile function. In the PD arm we administered
      validated questionnaires to determine the erectile function status by the
      International Index of Erectile Function 5 (IIEF-5) and the pain status during
      erection by the Visual Analogue Scale (VAS). A univariate analysis was conducted
      using R software. RESULTS: We enrolled 279 consecutive patients. The number of PD
      patients was 97 (34,7%). The univariate analysis showed a correlation between PD
      and cigarette smoking (p = 0.0242), blood hypertension (p < 0.001), erectile
      dysfunction (p < 0.001). No significant association was observed between diabetes
      and PD (p = 0.358). The median age of PD arm was 60 years and the median age of
      the control arm was 63,5 years; therefore the median age of PD arm resulted lower
      than the median age of the control arm (p = 0,031). CONCLUSIONS: Peyronie's
      disease is more common than we might think; furthermore it can be diagnosed among
      young patients. According to our results, cigarette smoking and blood
      hypertension may be considered statically significant risk factors for developing
      PD. On the contrary diabetes seems not to be a risk factor for PD. According to
      our results PD should be sought also in young patients. Further studies are
      necessary to confirm that removing the indicated risk factors may reduce the
      incidence of PD.

PMID- 25847892
TI  - Effectiveness on urinary symptoms and erectile function of Prostamev Plus(r) vs
      only extract Serenoa repens.
AB  - Prostatic inflammation is widespread in the male population. Two groups of 50
      patients each with symptoms of prostatic inflammation and ecocolorDoppler
      indicative of prostatitis were identified. Both groups were further subdivided
      into two subgroups (respectively A1, A2, B1, and B2). Group A1 underwent therapy
      with oral levofloxacin 500 mg daily for 10 days plus co-treatment with oral
      Serenoa repens (320 mg) plus Bromeline plus Nettle (Prostamev Plus(r)) daily for
      two months; Group A2 with oral levofloxacin 500 mg daily for 10 days plus oral
      Serenoa repens extract 320 mg/day for two months; Group B1 specific antibiotic
      treatment for 10 days (included levofloxacin if sensitive) plus co-treatment with
      oral Serenoa repens (320 mg) plus Bromeline plus Nettle (Prostamev Plus(r)) daily
      for two months; Group B2 with specific antibiotic treatment for 10 days plus
      Serenoa repens 320 mg/day for two months. The groups treated with Prostamev
      Plus(r) in comparison to the groups treated with Serenoa repens extract (saw
      palmetto) achieved better improvements of both IPSS score, urinary flow and
      sexual life. 

PMID- 25847893
TI  - A conservative approach to perineal Fournier's gangrene.
AB  - Fournier's gangrene (FG) is a disease involving necrosis of perineum and external
      genitalia; in 95% of cases it is possible to diagnose the Fournier's gangrene
      just by physical examination. The clinical presentation of FG varies from an
      initial localized infection to large areas with necrotizing infection. The
      disease typically affect elderly men (6 degrees -7 degrees  decade) with
      important systemic comorbidities; women are less frequently affected. Despite
      improvements in diagnosis and management, the mortality rate nowadays is between
      20% and 43%. The severity and mortality of the disease is dependent upon the
      general condition of the patient at presentation and upon the rate of spread of
      the infection. Treatment involves a multidisciplinary approach: intensive
      systematic management, broad-spectrum antibiotic therapy, early surgical
      debridement (wide abscission of necrotic tissues and surgical drainage of
      peritoneum, scrotum, penis, and inguinal areas), hyperbaric oxygen therapy;
      surgery can eventually be repeated if necessary; reconstructive surgery has an
      important role in the final treatment of the disease. The technical difficulties
      frequently encountered and the inability to make a complete removal of the
      necrotizing tissues at the time of surgery in some cases has led to the
      application of combined techniques, in view of the enhancement effect of specific
      advanced medications, targeted antibiotic therapy and hyperbaric medicine. We
      have considered 6 patients affected by Fournier's gangrene treated at our
      institution; all the patients received treatment with the help of plastic
      surgeons of the same institution. After debridement, all the patients were
      treated with advanced specific dressings consisting of plates and strips made of
      calcium alginate, hydrogels and polyurethane and twodimensional cavity foams.
      Reconstructive surgery was necessary in one case. Hyperbaric oxygen therapy (HBO)
      has been performed in all cases. The multidisciplinary approach, the combined use
      of HBO therapy and the adoption of advanced specific dressings, have made
      possible the complete healing of the lesions in a shorter period, avoiding
      further surgery in 5 out of 6 patients. 

PMID- 25847894
TI  - Is it possible to predict the need of inguinal lymphadenectomy in patients with
      squamous cell carcinoma of the penis? A clinical and a pathological study.
AB  - OBJECTIVE: to investigate the role of CD- 44 immunohistochemical expression
      within tumoural and non-tumoural tissue, aiming to understand if it can help us
      to predict the need of performing inguinal lymph nodes dissection to complete
      surgery of the penis. MATERIALS AND METHODS: CD44 immunohistochemical expression
      was investigated in tissue specimens from 39 patients with squamous cell
      carcinoma of the penis who underwent partial or total penectomy between 1987 and
      2008. Patient age, tumour size, and grade; CD44 intensity score, cytological
      expression, topographic and distribution pattern were evaluated by
      immunohistochemistry on archived material and correlated with disease-specific
      survival. RESULTS: mean patients age was 67.7 years; mean followup was 130.44
      months. Bilateral inguinal lymphadenectomy was performed in 14 patients; there
      were 8 N+ patients (23.5%). pTis-pT1 vs. > pT1 and the EAU classification of risk
      group resulted to be predictive of lymph nodal metastases at univariate analysis
      (respectively p = 0.006 and p = 0.045), but not the grading. The intensity score,
      cytological expression, topographic and distribution pattern of CD44 staining did
      not correlate with stage, grade and lymph nodes metastases. All disease related
      deaths occurred only in patients showing an high CD44 intratumoral expression,
      but this correlation is not statistically significant. Multivariate analysis
      showed that only lymph node metastasis was an independent prognostic factor
      predictive of lymph nodes metastases. CONCLUSIONS: CD44 expression in patients
      with squamous cell carcinoma of the penis is not able to predict the need of
      performing inguinal lymphadenectomy; staging and the EAU classification of risk
      group resulted to be predictive of lymph nodal metastases.

PMID- 25847895
TI  - The effect of inclined position on stone free rates in patients with lower
      caliceal stones during SWL session.
AB  - OBJECTIVE: To compare the outcomes of shock wave lithotripsy (SWL) combined with
      inclined position and SWL alone in patients with lower pole calyx stones.
      METHODS: Seven hundred forty patients who underwent SWL treatment for lower pole
      renal stones with a total diameter of 2 cm or less were prospectively randomized
      into two groups. They were comparable in terms of age, sex, and stone diameters.
      Patients with lower calyceal stones (4-20 mm) were randomized to SWL (368
      patients) or SWL with simultaneous inclination (372 patients) with 30o head down
      Trendelenburg position). Shock wave and session numbers were standardized
      according to stone size. Additional standardized shock waves were given to
      patients with stone fragments determined by kidney urinary bladder film and
      ultrasound at weeks 1, 4, 10. RESULTS: The overall stone free rate (SFR) was 73%
      (268/368) in patients with SWL alone and 81% (300/372) in SWL with inclination at
      the end of 12th week (p = 0.015). No significant adverse events were noted in
      both treatment groups. CONCLUSION: Simultaneous inclination of patients during
      SWL session increase SFR in lower caliceal stones significantly compared to SWL
      treatment alone.

PMID- 25847896
TI  - Comparing robotic, laparoscopic and open cystectomy: a systematic review and meta
      analysis.
AB  - OBJECTIVE: To conduct a systematic review and meta-analysis comparing outcomes
      between Open Radical Cystectomy (ORC), Laparoscopic Radical Cystectomy (LRC) and
      Robot-assisted Radical Cystectomy (RARC). RARC is to be compared to LRC and ORC
      and LRC compared to ORC. MATERIAL AND METHODS: A systematic review of the
      literature was conducted, collating studies comparing RARC, LRC and ORC. Surgical
      and oncological outcome data were extracted and a meta-analysis was performed.
      RESULTS: Twenty-four studies were selected with total of 2,104 cases analyzed.
      RARC had a longer operative time (OPT) compared to LRC with no statistical
      difference between length of stay (LOS) and estimated blood loss (EBL). RARC had
      a significantly shorter LOS, reduced EBL, lower complication rate and longer OPT
      compared to ORC. There were no significant differences regarding lymph node yield
      (LNY) and positive surgical margins (PSM.) LRC had a reduced EBL, shorter LOS and
      increased OPT compared to ORC. There was no significant difference regarding LNY.
      CONCLUSION: RARC is comparable to LRC with better surgical results than ORC. LRC
      has better surgical outcomes than ORC. With the unique technological features of
      the robotic surgical system and increasing trend of intra-corporeal
      reconstruction it is likely that RARC will become the surgical option of choice.

PMID- 25847897
TI  - Evaluation of laparoscopic vs robotic partial nephrectomy using the margin,
      ischemia and complications score system: a retrospective single center analysis.
AB  - OBJECTIVE: To evaluate differences between Laparoscopic Partial Nephrectomy (LPN)
      and Robot-Assisted Partial Nephrectomy (RAPN) using the Margin, Ischemia and
      Complications (MIC) score system and to evaluate factors related with MIC
      success. MATERIALS AND METHODS: Single centre retrospective study on 258 LPN and
      58 RAPN performed between January 2012 and January 2014. Success was defined when
      surgical margins was negative, Warm Ischemia Time (WIT) was <= 20 minutes and no
      major complications occurred. Mann-Whitney-U and Pearson chi2 correlation were
      used to compare LPN and RAPN. A matched pair comparison was also performed.
      Spearman correlation (Rho) was used to evaluate the relationship between
      clinical, intra and post-operative and pathological patients characteristics with
      MIC score. A binary regression analysis was also performed to evaluate
      independent factors associated with MIC success. RESULTS: The MIC rate in LPN and
      RAPN was 55% and 65.5% respectively. No differences in clinical, intra and post
      operative outcomes between groups were found. Clinical tumor size (p-value: <
      0.001; OR: 0.829; 95% CI: 0.697-0.987), PADUA score (p-value: < 0.001; OR: 0.843;
      95% CI: 0.740-0.960), PADUA risk groups (intermediate; p-value: < 0.001; OR:
      0.416; 95% CI: 0.238- 0.792; high: p-value: < 0.001; OR: 0.356; 95% CI: 0.199-
      0.636), WIT (p-value: < 0.001; OR: 0.598; 95% CI: 0.530- 0.675) were
      independently associated with MIC. eGFR (< 60 vs >= 60 ml/min per 1.73 m2: p
      value: < 0.001; OR: 3.356; 95% CI: 1.701-6.621) and Fuhrman nuclear grade (p
      value: 0.014; OR: 1.798; 95% CI:1.129-2.865) were also independently associated
      with MIC. CONCLUSIONS: MIC score system is a simple and useful tool to report and
      to compare different surgical approach.

PMID- 25847898
TI  - Change of practice patterns in urology with the introduction of the Da Vinci
      surgical system: the Greek NHS experience in debt crisis era.
AB  - OBJECTIVE: To determine the attitudinal change for urologic surgery in Greece
      since the introduction of the da Vinci Surgical System (DVS). We describe
      contemporary trends at public hospital level, the initial Greek experience, while
      at the same time Greece is in economic crisis and funding is under austerity
      measures. MATERIALS AND METHODS: We retrospectively analyzed annualized case log
      data on urologic procedures, between 2008 (installation of the DVS) and 2013,
      from "Laiko'' Hospital in Athens. We evaluated, using summary statistics, trends
      and institutional status regarding robot-assisted surgery (RAS). We also analyzed
      the relationship between the introduction of RAS and change in total volume of
      procedures performed. RESULTS: 1578 of the urological procedures performed at
      "Laiko'' Hospital were pooled, 1342 (85%) being open and 236 RAS (15%). We
      observed a 6-fold increase in the number of RAS performed, from 7% of the total
      procedural volume (14/212) in 2008 to 30% (96/331) in 2013. For radical
      prostatectomy, in 2008 2% were robot-assisted and 98% open while in 2013, 46% and
      54% respectively. Pyeloplasty was performed more often using the robot-assisted
      method since 2010. RAS-dedicated surgeons increased both RAS and the total number
      of procedures they performed. From 86 in 2008 to 145 in 2013, with 57% of them
      being RAS in 2013 as compared to 13 % in 2008. CONCLUSIONS: Robot-assisted
      surgery has integrated into the armamentarium for urologic surgery in Greece at
      public hospital level. Surgical robot acquisition is also associated with
      increased volume of procedures, especially prostatectomy, despite the ongoing
      debate over cost-effectiveness, during economic crisis and International Monetary
      Fund (IFN) era.

PMID- 25847899
TI  - Effect of immobilization on urine calcium excretion in orthopedic patients with
      pelvic fracture treated by skin traction.
AB  - OBJECTIVES: To determine the effects on urine calcium excretion of immobilization
      by skin traction in patients with pelvic fracture. METHODS: In a prospective
      study, a consecutive series of patients with pelvic fracture treated by skin
      traction were enrolled. Serum (calcium, phosphorous, alkaline phosphatase,
      sodium, potassium, uric acid, BUN, creatinine) and fasting urine calcium,
      creatinine, sodium, potassium and uric acid were checked within 48 hours of
      hospitalization and at 7, 14 and 21 days of immobilization and then after 3
      months of mobilization. Trends in changes of variables were recorded. RESULTS:
      Fifty five patients were enrolled in this study; they were 45 (81.8%) males and
      10 (18.2%) females with a mean age 19.4 +/- 12.7 years. We found that serum
      levels of calcium (p = 0.004), phosphorous (p = 0.047) and alkaline phosphatase
      (p = 0.001) increased significantly during the 3 weeks of immobilization. In the
      same way, urine calcium/ urine creatinine ratio increased significantly in the
      study period (p = 0.004). No symptomatic renal stone formation was observed
      during the study period. CONCLUSIONS: Immobilization even in short term causes
      hypercalciuria in orthopedic patients. Although it is transient and improves with
      subsequent mobilization, it is needed to be considered specifically by the team
      caring for this group of patients.

PMID- 25847900
TI  - Use of cinacalcet in nephrolithiasis associated with normocalcemic or
      hypercalcemic primary hyperparathyroidism: results of a prospective randomized
      pilot study.
AB  - OBJECTIVES: To evaluate, by means of a prospective randomized study, the efficacy
      of cinacalcet in the forms of nephrolithiasis associated with primary
      hyperparathyroidism in both the hypercalcemic and normocalcemic variant.
      MATERIALS AND METHODS: Ten patients suffering from active nephrolithiasis
      associated with primary hyperparathyroidism (4 hypercalcemics and 6
      normocalcemics), equally divided between males and females, were randomly but not
      blindly addressed to treatment with potassium citrate and allopurinol, or to the
      same therapeutic regimen in combination with cinacalcet. The dosage of cinacalcet
      was optimized for each patient in order to obtain a reduction of parathyroid
      hormone (PTH) within normal limits while enabling the maintenance of adequate
      calcemic values. All study participants were given the same diet based on a
      reduction in sodium intake, oxalate-rich foods and animal protein with
      standardized intake of calcium and an increase in hydration. After a follow up
      period of 10 months , cinacalcet was associated to standard therapy and diet in
      patients who were not taken it, conversely cinacalcet was withdrawn in the
      remaining patients who remained on standard therapeutic regimen and diet. Follow
      up was continued for a second period of observation of the same duration of the
      first. RESULTS: At the end of the period of treatment with cinacalcet, for both
      variants of hyperparathyroidism, a statistically significant reduction in the
      overall number and in the diameter of renal stones was found. CONCLUSIONS: This
      prospective randomized study shows the effectiveness of cinacalcet used in
      combination with a diet with normalized calcium intake, in reducing the number
      and size of urinary stones in hypercalemic and normocalcemic forms of primary
      hyperparathyroidism.

PMID- 25847901
TI  - Is routine ureteral stenting really necessary after retrograde intrarenal
      surgery?
AB  - OBJECTIVES: To investigate the situations in which ureteral double-J stent should
      be used after retrograde intrarenal surgery (RIRS). PATIENTS AND METHODS:
      Patients with no ureteral double-J stent after RIRS constituted Group 1, and
      those with double- J stent after RIRS constituted Group 2. Patients' age and
      gender, renal stone characteristics (location and dimension), stone-free status,
      VAS score 8 hours after surgery, post-procedural renal colic attacks, length of
      hospitalization, requirement for re-hospitalization, time to rehospitalization
      and secondary procedure requirements were analyzed. RESULTS: RIRS was performed
      on 162 renal units. Double-J stent was used in 121 (74.6%) of these after RIRS,
      but not in the other 41 (25.4%). At radiological monitoring at the first month
      postoperatively after RIRS, complete stone-free status was determined in 122
      (75.3%) renal units, while residual stone was present in 40 (24.6%). No
      significant differences were observed between the groups in terms of duration of
      fluoroscopy (p = 0.142), operation (p = 0.108) or hospitalization times (p =
      0.798). VAS values determined routinely on the evening of surgery were
      significantly higher in Group 1 than in Group 2 (p = 0.025). Twenty-eight (17.2%)
      presentations were made to the emergency clinic due to renal colic within 1 month
      after surgery. Double-J catheter was present in 24 (85.7%) of these patients.
      CONCLUSIONS: Routine double-J stent insertion after RIRS is not essential since
      it increases costs, morbidity and operation time.

PMID- 25847902
TI  - Relevance of prostate cancer in patients with synchronous invasive bladder
      urothelial carcinoma: a monocentric retrospective analysis.
AB  - OBJECTIVES: We retrospectively reviewed data of patients with incidental prostate
      cancer (PCa) who underwent radical cystoprostatectomy (RCP) for invasive bladder
      cancer and we analyzed their features with regard to incidence, pathologic
      characteristics, clinical significance, and implications for management. MATERIAL
      AND METHODS: Clinical data and pathological features of 64 patients who underwent
      standard RCP for bladder cancer were included in this study. Besides the
      urothelial carcinoma of the urinary bladder, the location and tumor volume of the
      PCa, prostate apex involvement, Gleason score, pathological staging and surgical
      margins were evaluated. Clinically significant PCa was defined as a tumor with a
      Gleason 4 or 5 pattern, stage >= pT3, lymph node involvement, positive surgical
      margin or multifocality of three or more lesions. Postoperative follow-up was
      scheduled every 3 months in the first year, every 6 months in the second and
      third year, annually thereafter. RESULTS: 11 out of 64 patients (17.2%) who
      underwent RCP had incidentally diagnosed PCa. 3 cases (27.3%) were diagnosed as
      significant PCa, while 8 cases (72.7%) were clinically insignificant. The
      positive surgical margin of PCa was detected in 1 patient with significant
      disease. The prostate apex involvement was present in 1 patient of the
      significant PCa group. Median follow-up period was 47.8 +/- 29.2 (range 4-79).
      During the follow-up, biochemical recurrence occurred in 1 patient (9%).
      Concerning the cancer specific survival there was no statistical significance (P
      = 0.326) between the clinically significant and clinical insignificant cancer
      group. CONCLUSIONS: In line with published studies, incidental PCa does not
      impact on the prognosis of bladder cancer of patients undergoing RCP.

PMID- 25847903
TI  - Effect of microorganisms on etiology of hematospermia.
AB  - BACKGROUND: Hematospermia is the presence of blood in the ejaculate. Its etiology
      is congenital, inflammatory, infectious, obstructive, tumoral, vascular,
      traumatic, iatrogenic or related to systemic disease. It is a quite irritating
      and life-quality-disturbing condition for men. It is significant to demonstrate
      infectious-based hematospermia due to the fact that its treatment is easier than
      for other reasons. METHODS: 30 patients, having spontaneous hematospermia, were
      taken to our study. The serum total PSA levels of the patients were examined and
      microbiological examinations such as direct inspection for ejaculate, routine
      bacteriological and mycetes culture, Gram staining, trichrome staining and
      Mycoplasma hominis/Ureaplasma urealyticum culture (Mycofast Evolution 3, ELITech,
      France) were performed. RESULTS: Bacteria was isolated in 11 (36%) of 30 patients
      with hematospermia. S.aureus occurred in five patients (45.5%), U.urealyticum in
      three patients (27.2%) and E.coli and K.pneumoniae in one each (9.1%).
      U.urealyticum and S.aureus occurred together in one patient. No statistical
      difference of scores of National Institute of Health-Chronic Prostatitis Symptoms
      Index (CPSI) and serum total PSA levels between the patients with and without
      infection was observed. CONCLUSIONS: Hematospermia mostly affects micturition
      functions of young men and it can be due to infection in one-third of the cases.

PMID- 25847904
TI  - Urolithiasis is associated with low serum testosterone levels in men.
AB  - OBJECTIVE: To evaluate the relationship among urolithiasis, metabolic syndrome
      (MetS) and serum testosterone (T) level in men. MATERIAL AND METHODS: 513 men
      older than 18 years were enrolled in this study: 313 of the subjects had a
      history of stones (group 1) and 200 had no history of stones (controls, group 2).
      Early morning T levels were recorded and anthropometric measurements were
      investigated to evaluate MetS. Analyses were completed using chi-square tests.
      RESULT: Serum T level was lower in stone forming patients than control subjects
      and 161 (%51.4) men in group 1 and 92 (%46) men in group 2 were diagnosed with
      metabolic syndrome. T level was found lower limit (< 285 ng/dl) in the MetS and
      urolithiasis group (p 0.002, OR 2.71). CONCLUSIONS: We found low testosterone
      levels in the patients with stone disease and prevalence of the MetS in men with
      urolithiasis was higher than in men without stone disease. Our findings show that
      levels of testosterone had no effect on stone formation, but the factors that
      cause stone formation can have an effect on the level of testosterone.

PMID- 25847905
TI  - Unusual case of locally advanced and metastatic paratesticular liposarcoma: a
      case report and review of the literature.
AB  - Liposarcoma accounts for 20% of all sarcomas and is a rare occurrence in the
      paratesticular region. We present the case of a 66-year-old man with a massive
      liposarcoma of the right scrotum invading the lower limb and the abdominal wall
      skin. The case concerns an unusually large and aggressive liposarcoma (25 cm),
      presenting with multiple lung and nodal metastases. The patient had an
      unfavourable evolution with rapid progression of metastases, although there were
      no signs of local disease. In this case, a wide local excision was performed in
      order to obtain local control of the disease. Even though paratesticular sarcomas
      might have a more favourable evolution, the association with lung involvement
      carries an ominous prognosis. Diagnosis of paratesticular sarcoma should be kept
      in mind in case of irregular necrotic masses in the inguinal and scrotal region. 

PMID- 25847906
TI  - An unusual case of intrarenal coiled and ruptured guidewire.
AB  - OBJECTIVE: To the best of our knowledge there are only 3 reports of fractured
      guidewires inside the pelvicalyceal system, successfully removed with endourology
      techniques, and this is the first one presenting a tightly coiled
      intraparenchymal section. MATERIAL AND METHODS: A 59-year-old woman was
      hospitalized for surgical treatment of a right kidney of reduced size. Past
      history revealed pyelolithotomy for a staghorn stone 14 months earlier at another
      Institution with subsequent ureteral obstruction, one failed attempt at ureteral
      double-J catheter insertion and one failed attempt at percutaneous nephrostomy
      placement 5 months postoperatively. Another nephrostomy was placed, but left
      indwelling briefly. CT scan demonstrated a small-size kidney with residual stone
      fragments and presence of a "device" in the lower pole. The tapered distal
      extremity of an hydrophilic guidewire, with a tightly coiled central section
      wedged in the renal tissue was found inside the nephrectomy specimen. RESULTS:
      While the Radiologist who read the CT scan hypothesized that the "device" was a
      fragment of double-J ureteral stent or nephrostomy catheter, it consisted of the
      hydrophilic extremity of a guidewire, broken during a previous attempt at
      nephrostomy placement. Perirenal fibrosis and inappropriate angle between the
      needle and the lower calyx are the likely causes of guidewire coiling during its
      advancement and subsequent rupture during withdrawal. CONCLUSIONS: Urologists
      must be aware that, although percutaneous nephrostomy has a very high technical
      success rate, unusual complications like guidewire fracture may occur, and that
      modern imaging techniques can provide an accurate picture of this condition.

PMID- 25847907
TI  - Ischemia of the glans penis following circumcision: case report and revision of
      the literature.
AB  - Ischemic complications of the glans penis are rare and commonly result from
      trauma, inadvertent administration of vasoconstrictive solutions, diabetes
      mellitus, circumcision and vasculitis; we refer about a young man with severe
      ischemia of the glans penis following circumcision. The patient had undergone
      circumcision 5 days before in a surgery department under local anesthesia (1%
      mepivacaine hydrochloride). The patient noticed a brownish color and edema of the
      glans penis at 24 h after he opened the wound dressing, but arrived to our
      hospital only 5 days after circumcision because these findings had progressed.
      Physical examination revealed the black color or necrotic appearance of the glans
      penis, and edema on the dorsal penile skin. The patient underwent antibiotic,
      antiplatatelet, corticosteroid and iperbaric therapy achieving a complete
      restitutio ad integrum. 

PMID- 25847908
TI  - Complete intraperitoneal displacement of a double J stent: a first case.
AB  - OBJECTIVES: Ureteral double-J stents are known to migrate proximally and distally
      within the urinary tract, while perforation and stent displacement are uncommon.
      Possible mechanisms of displacement are either original malpositioning with
      ureteral perforation or subsequent fistula and erosion of the excretory system,
      due to infection or long permanence of the device. We present the unique case of
      complete intraperitoneal stent migration in a 59-year-old caucasian male without
      evidence of urinary fistula at the moment of diagnosis, so far an unreported
      complication. MATERIALS AND METHODS: Eight months after the placement of a double
      J stent for lower right ureteral stricture at a district hospital, the patient
      came at our observation for urosepsis and hydro-uretero-nephrosis. A CT scan
      demonstrated intraperitoneal migration of the stent outside the urinary tract.
      Cystoscopy failed to visualize the lower extremity of the stent, a percutaneous
      nephrostomy was placed to drain the urinary system and the stent was removed
      through a small abdominal incision on the right lower quadrant. RESULTS: In our
      case we presume that during the positioning manoeuvre the guide wire perforated
      simultaneously the lower ureteral wall and the pelvic peritoneum, and that once
      the upper end of the stent was coiled, the lower extremity was also attracted
      intraperitoneally. The lack of pain due to the spinal lesion concurred to this
      unusual complication. CONCLUSIONS: We must be aware that ureteral double J stents
      may be found displaced even inside the peritoneal cavity, and that the use of
      retrograde pyelography during placement is of paramount importance to exclude
      misplacement of an apparently normally coiled upper extremity of the stent.

PMID- 25847909
TI  - A very rare case of adult-type granulosa cell tumor.
AB  - Granulosa cell tumor (GST) of the testis is a rare neoplasm. Here we describe a
      case of an adult type GST. More than a year after surgical treatment, without any
      other treatment, the patient is alive without sign of disease. 

PMID- 25847911
TI  - Generalized linear mixed models for multi-reader multi-case studies of diagnostic
      tests.
AB  - Diagnostic tests are often compared in multi-reader multi-case (MRMC) studies in
      which a number of cases (subjects with or without the disease in question) are
      examined by several readers using all tests to be compared. One of the commonly
      used methods for analyzing MRMC data is the Obuchowski-Rockette (OR) method,
      which assumes that the true area under the receiver operating characteristic
      curve (AUC) for each combination of reader and test follows a linear mixed model
      with fixed effects for test and random effects for reader and the reader-test
      interaction. This article proposes generalized linear mixed models which
      generalize the OR model by incorporating a range-appropriate link function that
      constrains the true AUCs to the unit interval. The proposed models can be
      estimated by maximizing a pseudo-likelihood based on the approximate normality of
      AUC estimates. A Monte Carlo expectation-maximization algorithm can be used to
      maximize the pseudo-likelihood, and a non-parametric bootstrap procedure can be
      used for inference. The proposed method is evaluated in a simulation study and
      applied to an MRMC study of breast cancer detection.

PMID- 25847912
TI  - Some comments on "The analysis of multivariate longitudinal data: A review".
AB  - We provide a commentary on "The analysis of multivariate longitudinal data: a
      review" by Verbeke et al. The authors provide a comprehensive review of the
      issues in the analysis of multivariate longitudinal data and use examples to
      demonstrate the pros and cons of several approaches. In this commentary, we
      indicate some important omissions in their review paper.

PMID- 25847910
TI  - Techniques to improve detection and analysis of extracellular vesicles using flow
      cytometry.
AB  - Extracellular vesicles (EVs) range in size from 50 nm to 1 um. Flow cytometry
      (FCM) is the most commonly used method for analyzing EVs; however, accurate
      characterization of EVs remains challenging due to their small size and lack of
      discrete positive populations. Here we report the use of optimization techniques
      that are especially well-suited for analyzing EVs from a high volume of clinical
      samples. Utilizing a two pronged approach that included 1) pre-filtration of
      antibodies to remove aggregates, followed by 2) detergent lysis of a replicate
      sample to account for remaining false positive events, we were able to
      effectively limit false positive non-EV events. In addition, we show that lysed
      samples are a useful alternative to isotypes for setting gates to exclude
      background fluorescence. To reduce background, we developed an approach using
      filters to "wash" samples post-staining thus providing a faster alternative to
      ultracentrifugation and sucrose gradient fractionation. In conclusion, use of
      these optimized techniques enhances the accuracy and efficiency of EV detection
      using FCM.

PMID- 25847914
TI  - Comprehensive evaluation of poly(I:C) induced inflammatory response in an airway
      epithelial model.
AB  - Respiratory viruses invade the upper airway of the lung, triggering a potent
      immune response that often exacerbates preexisting conditions such as asthma and
      COPD. Poly(I:C) is a synthetic analog of viral dsRNA that induces the
      characteristic inflammatory response associated with viral infection, such as
      loss of epithelial integrity, and increased production of mucus and inflammatory
      cytokines. Here, we explore the mechanistic responses to poly(I:C) in a well
      defined primary normal human bronchial epithelial (NHBE) model that recapitulates
      in vivo functions and responses. We developed functional and quantifiable methods
      to evaluate the physiology of our model in both healthy and inflamed states.
      Through gene and protein expression, we validated the differentiation state and
      population of essential cell subtypes (i.e., ciliated, goblet, club, and basal
      cells) as compared to the human lung. Assays for total mucus production, cytokine
      secretion, and barrier function were used to evaluate in vitro physiology and
      response to viral insult. Cells were treated apically with poly(I:C) and
      evaluated 48 h after induction. Results revealed a dose-dependent increase in
      goblet cell differentiation, as well as, an increase in mucus production relative
      to controls. There was also a dose-dependent increase in secretion of IL-6, IL-8,
      TNF-alpha, and RANTES. Epithelial barrier function, as measured by TEER, was
      maintained at 1501 +/- 355 Omega*cm2 postdifferentiation, but dropped
      significantly when challenged with poly(I:C). This study provides first steps
      toward a well-characterized model with defined functional methods for
      understanding dsRNA stimulated inflammatory responses in a physiologically
      relevant manner. 

PMID- 25847915
TI  - Reduced fitness and abnormal cardiopulmonary responses to maximal exercise
      testing in children and young adults with sickle cell anemia.
AB  - Physiologic contributors to reduced exercise capacity in individuals with sickle
      cell anemia (SCA) are not well understood. The objective of this study was to
      characterize the cardiopulmonary response to maximal cardiopulmonary exercise
      testing (CPET) and determine factors associated with reduced exercise capacity
      among children and young adults with SCA. A cross-sectional cohort of 60 children
      and young adults (mean 15.1 +/- 3.4 years) with hemoglobin SS or S/beta(0)
      thalassemia and 30 matched controls (mean 14.6 +/- 3.5 years) without SCA or
      sickle cell trait underwent maximal CPET by a graded, symptom-limited cycle
      ergometry protocol with breath-by-breath, gas exchange analysis. Compared to
      controls without SCA, subjects with SCA demonstrated significantly lower peak VO2
      (26.9 +/- 6.9 vs. 37.0 +/- 9.2 mL/kg/min, P < 0.001). Subjects demonstrated
      slower oxygen uptake (DeltaVO2/DeltaWR, 9 +/- 2 vs. 12 +/- 2 mL/min/watt, P <
      0.001) and lower oxygen pulse (DeltaVO2/DeltaHR, 12 +/- 4 vs. 20 +/- 7 mL/beat, P
      < 0.001) as well as reduced oxygen uptake efficiency (DeltaVE/DeltaVO2, 42 +/- 8
      vs. 32 +/- 5, P < 0.001) and ventilation efficiency (DeltaVE/DeltaVCO2, 30.3 +/-
      3.7 vs. 27.3 +/- 2.5, P < 0.001) during CPET. Peak VO2 remained significantly
      lower in subjects with SCA after adjusting for age, sex, body mass index (BMI),
      and hemoglobin, which were independent predictors of peak VO2 for subjects with
      SCA. In the largest study to date using maximal CPET in SCA, we demonstrate that
      children and young adults with SCA have reduced exercise capacity attributable to
      factors independent of anemia. Complex derangements in gas exchange and oxygen
      uptake during maximal exercise are common in this population. 

PMID- 25847916
TI  - The influence of sighing respirations on infant lung function measured using
      multiple breath washout gas mixing techniques.
AB  - There is substantial interest in studying lung function in infants, to better
      understand the early life origins of chronic lung diseases such as asthma.
      Multiple breath washout (MBW) is a technique for measuring lung function that has
      been adapted for use in infants. Respiratory sighs occur frequently in young
      infants during natural sleep, and in accordance with current MBW guidelines,
      result in exclusion of data from a substantial proportion of testing cycles. We
      assessed how sighs during MBW influenced the measurements obtained using data
      from 767 tests conducted on 246 infants (50% male; mean age 43 days) as part of a
      large cohort study. Sighs occurred in 119 (15%) tests. Sighs during the main part
      of the wash-in phase (before the last 5 breaths) were not associated with
      differences in standard MBW measurements compared with tests without sighs. In
      contrast, sighs that occurred during the washout were associated with a small but
      discernible increase in magnitude and variability. For example, the mean lung
      clearance index increased by 0.36 (95% CI: 0.11-0.62) and variance increased by a
      multiplicative factor of 2 (95% CI: 1.6-2.5). The results suggest it is
      reasonable to include MBW data from testing cycles where a sigh occurs during the
      wash-in phase, but not during washout, of MBW. By recovering data that would
      otherwise have been excluded, we estimate a boost of about 10% to the final
      number of acceptable tests and 6% to the number of individuals successfully
      tested. 

PMID- 25847917
TI  - Effects of Lactobacillus johnsonii and Lactobacillus reuteri on gut barrier
      function and heat shock proteins in intestinal porcine epithelial cells.
AB  - Heat shock proteins (HSPs) are a set of highly conserved proteins that can serve
      as intestinal gate keepers in gut homeostasis. Here, effects of a probiotic,
      Lactobacillus rhamnosus GG (LGG), and two novel porcine isolates, Lactobacillus
      johnsonii strain P47-HY and Lactobacillus reuteri strain P43-HUV, on
      cytoprotective HSP expression and gut barrier function, were investigated in a
      porcine IPEC-J2 intestinal epithelial cell line model. The IPEC-J2 cells
      polarized on a permeable filter exhibited villus-like cell phenotype with
      development of apical microvilli. Western blot analysis detected HSP expression
      in IPEC-J2 and revealed that L. johnsonii and L. reuteri strains were able to
      significantly induce HSP27, despite high basal expression in IPEC-J2, whereas LGG
      did not. For HSP72, only the supernatant of L. reuteri induced the expression,
      which was comparable to the heat shock treatment, which indicated that HSP72
      expression was more stimulus specific. The protective effect of lactobacilli was
      further studied in IPEC-J2 under an enterotoxigenic Escherichia coli (ETEC)
      challenge. ETEC caused intestinal barrier destruction, as reflected by loss of
      cell-cell contact, reduced IPEC-J2 cell viability and transepithelial electrical
      resistance, and disruption of tight junction protein zonula occludens-1. In
      contrast, the L. reuteri treatment substantially counteracted these detrimental
      effects and preserved the barrier function. L. johnsonii and LGG also achieved
      barrier protection, partly by directly inhibiting ETEC attachment. Together, the
      results indicate that specific strains of Lactobacillus can enhance gut barrier
      function through cytoprotective HSP induction and fortify the cell protection
      against ETEC challenge through tight junction protein modulation and direct
      interaction with pathogens. 

PMID- 25847918
TI  - Leaky intestine and impaired microbiome in an amyotrophic lateral sclerosis mouse
      model.
AB  - Emerging evidence has demonstrated that intestinal homeostasis and the microbiome
      play essential roles in neurological diseases, such as Parkinson's disease.
      Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease
      characterized by a progressive loss of motor neurons and muscle atrophy.
      Currently, there is no effective treatment. Most patients die within 3-5 years
      due to respiratory paralysis. Although the death of motor neurons is a hallmark
      of ALS, other organs may also contribute to the disease progression. We examined
      the gut of an ALS mouse model, G93A, which expresses mutant superoxide dismutase
      (SOD1(G93A)), and discovered a damaged tight junction structure and increased
      permeability with a significant reduction in the expression levels of tight
      junction protein ZO-1 and the adherens junction protein E-cadherin. Furthermore,
      our data demonstrated increased numbers of abnormal Paneth cells in the intestine
      of G93A mice. Paneth cells are specialized intestinal epithelial cells that can
      sense microbes and secrete antimicrobial peptides, thus playing key roles in host
      innate immune responses and shaping the gut microbiome. A decreased level of the
      antimicrobial peptides defensin 5 alpha was indeed found in the ALS intestine.
      These changes were associated with a shifted profile of the intestinal
      microbiome, including reduced levels of Butyrivibrio Fibrisolvens, Escherichia
      coli, and Fermicus, in G93A mice. The relative abundance of bacteria was shifted
      in G93A mice compared to wild-type mice. Principal coordinate analysis indicated
      a difference in fecal microbial communities between ALS and wild-type mice. Taken
      together, our study suggests a potential novel role of the intestinal epithelium
      and microbiome in the progression of ALS. 

PMID- 25847919
TI  - Exploring miniaturized EEG electrodes for brain-computer interfaces. An EEG you
      do not see?
AB  - Electroencephalography (EEG) allows the study of the brain-behavior relationship
      in humans. Most of what we have learned with EEG was through observing the brain
      behavior relationship under well-controlled laboratory conditions. However, by
      reducing "normal" behavior to a minimum the ecological validity of the results
      can be limited. Recent developments toward mobile EEG solutions allow to study
      the brain-behavior relationship outside the laboratory in more natural
      situations. Besides mobility and robustness with respect to motion, mobile EEG
      systems should also interfere as little as possible with the participant's
      behavior. For example, natural interaction with other people could be hindered
      when it is obvious that a participant wears an EEG cap. This study evaluates the
      signal quality obtained with an unobtrusive solution for EEG monitoring through
      the integration of miniaturized EEG ton-electrodes into both a discreet baseball
      cap and an individualized ear piece. We show that such mini electrodes located at
      scalp and ear locations can reliably record event related potentials in a P300
      brain-computer-interface application. 

PMID- 25847920
TI  - Lower limb conduit artery endothelial responses to acute upper limb exercise in
      spinal cord injured and able-bodied men.
AB  - Vascular improvements in the nonactive regions during exercise are likely
      primarily mediated by increased shear rate (SR). Individuals with spinal cord
      injury (SCI) experience sublesional vascular deconditioning and could potentially
      benefit from upper body exercise-induced increases in lower body SR. The present
      study utilized a single bout of incremental arm-crank exercise to generate
      exercise-induced SR changes in the superficial femoral artery in an effort to
      evaluate the acute postexercise impact on superficial femoral artery endothelial
      function via flow-mediated dilation (FMD), and determine regulatory factors in
      the nonactive legs of individuals with and without SCI. Eight individuals with
      SCI and eight age, sex, and waist-circumference-matched able-bodied (AB) controls
      participated. Nine minutes of incremental arm-crank exercise increased
      superficial femoral artery anterograde SR (P = 0.02 and P < 0.01), retrograde SR
      (P < 0.01 and P < 0.01), and oscillatory shear index (OSI) (P < 0.001 and P <
      0.001) in both SCI and AB, respectively. However, these SR alterations resulted
      in acute postexercise increases in FMD in the AB group only (SCI 6.0 +/- 1.2% to
      6.3 +/- 2.7%, P = 0.74; AB 7.5 +/- 1.4% to 11.2 +/- 1.4%, P = 0.03). While arm
      exercise has many cardiovascular benefits and results in changes in SR patterns
      in the nonactive legs, these changes are not sufficient to induce acute changes
      in FMD among individuals with SCI, and therefore are less likely to stimulate
      exercise training-associated improvements in nonactive limb endothelial function.
      Understanding the role of SR patterns on FMD brings us closer to designing
      effective strategies to combat impaired vascular function in both healthy and
      clinical populations. 

PMID- 25847921
TI  - mRNA expression of diacylglycerol kinase isoforms in insulin-sensitive tissues:
      effects of obesity and insulin resistance.
AB  - Diacylglycerol kinase (DGK) isoforms regulate signal transduction and lipid
      metabolism. DGKdelta deficiency leads to hyperglycemia, peripheral insulin
      resistance, and metabolic inflexibility. Thus, dysregulation of other DGK
      isoforms may play a role in metabolic dysfunction. We investigated DGK isoform
      mRNA expression in extensor digitorum longus (EDL) and soleus muscle, liver as
      well as subcutaneous and epididymal adipose tissue in C57BL/6J mice and obese and
      insulin-resistant ob/ob mice. All DGK isoforms, except for DGKkappa, were
      detectable, although with varying mRNA expression. Liver DGK expression was
      generally lowest, with several isoforms undetectable. In soleus muscle,
      subcutaneous and epididymal adipose tissue, DGKdelta was the most abundant
      isoform. In EDL muscle, DGKalpha and DGKzeta were the most abundant isoforms. In
      liver, DGKzeta was the most abundant isoform. Comparing obese insulin-resistant
      ob/ob mice to lean C57BL/6J mice, DGKbeta, DGKiota, and DGKtheta were increased
      and DGKepsilon expression was decreased in EDL muscle, while DGKbeta, DGKeta and
      DGKtheta were decreased and DGKdelta and DGKiota were increased in soleus muscle.
      In liver, DGKdelta and DGKzeta expression was increased in ob/ob mice. DGKeta was
      increased in subcutaneous fat, while DGKzeta was increased and DGKbeta, DGKdelta,
      DGKeta and DGKepsilon were decreased in epididymal fat from ob/ob mice. In both
      adipose tissue depots, DGKalpha and DGKgamma were decreased and DGKiota was
      increased in ob/ob mice. In conclusion, DGK mRNA expression is altered in an
      isoform- and tissue-dependent manner in obese insulin-resistant ob/ob mice. DGK
      isoforms likely have divergent functional roles in distinct tissues, which may
      contribute to metabolic dysfunction. 

PMID- 25847922
TI  - Time for a level playing field: inequalities in regulatory/approval processes-the
      example of bevacizumab in epithelial ovarian cancer.

PMID- 25847923
TI  - Problematic Use of Multiple Subgroup Analyses in Assessing the Impact of Aspirin
      in Prostate Cancer.

PMID- 25847924
TI  - Weighing the options for human epidermal growth factor receptor 2-directed
      therapy in metastatic breast cancer.

PMID- 25847926
TI  - Adoptive T-cell therapy is a promising salvage approach for advanced or recurrent
      metastatic cervical cancer.

PMID- 25847925
TI  - Long-term pulmonary function in survivors of childhood cancer.
AB  - PURPOSE: This study was undertaken to determine the magnitude of pulmonary
      dysfunction in childhood cancer survivors when compared with healthy controls and
      the extent (and predictors) of decline over time. PATIENTS AND METHODS: Survivors
      underwent baseline (t1) pulmonary function tests, followed by a second
      comprehensive evaluation (t2) after a median of 5 years (range, 1.0 to 10.3
      years). Survivors were also compared with age- and sex-matched healthy controls
      at t2. RESULTS: Median age at cancer diagnosis was 16.5 years (range, 0.2 to 21.9
      years), and time from diagnosis to t2 was 17.1 years (range, 6.3 to 40.1 years).
      Compared with odds for healthy controls, the odds of restrictive defects were
      increased 6.5-fold (odds ratio [OR], 6.5; 95% CI, 1.5 to 28.4; P < .01), and the
      odds of diffusion abnormalities were increased 5.2-fold (OR, 5.2; 95% CI, 1.8 to
      15.5; P < .01). Among survivors, age younger than 16 years at diagnosis (OR, 3.0;
      95% CI, 1.2 to 7.8; P = .02) and exposure to more than 20 Gy chest radiation (OR,
      5.6; 95% CI, 1.5 to 21.0; P = .02, referent, no chest radiation) were associated
      with restrictive defects. Female sex (OR, 3.9; 95% CI, 1.7 to 9.5; P < .01) and
      chest radiation dose (referent: no chest radiation; <= 20 Gy: OR, 6.4; 95% CI,
      1.7 to 24.4; P < .01; > 20 Gy: OR, 11.3; 95% CI, 2.6 to 49.5; P < .01) were
      associated with diffusion abnormalities. Among survivors with normal pulmonary
      function tests at t1, females and survivors treated with more than 20 Gy chest
      radiation demonstrated decline in diffusion function over time. CONCLUSION:
      Childhood cancer survivors exposed to pulmonary-toxic therapy are significantly
      more likely to have restrictive and diffusion defects when compared with healthy
      controls. Diffusion capacity declines with time after exposure to pulmonary-toxic
      therapy, particularly among females and survivors treated with high-dose chest
      radiation. These individuals could benefit from subsequent monitoring.

PMID- 25847927
TI  - Poison.

PMID- 25847928
TI  - Reply to M. Lee et al.

PMID- 25847929
TI  - Phase II Study of Gemcitabine, Carboplatin, and Iniparib As Neoadjuvant Therapy
      for Triple-Negative and BRCA1/2 Mutation-Associated Breast Cancer With Assessment
      of a Tumor-Based Measure of Genomic Instability: PrECOG 0105.
AB  - PURPOSE: This study was designed to assess efficacy, safety, and predictors of
      response to iniparib in combination with gemcitabine and carboplatin in early
      stage triple-negative and BRCA1/2 mutation-associated breast cancer. PATIENTS AND
      METHODS: This single-arm phase II study enrolled patients with stage I to IIIA (T
      >= 1 cm) estrogen receptor-negative (<= 5%), progesterone receptor-negative (<=
      5%), and human epidermal growth factor receptor 2-negative or BRCA1/2 mutation
      associated breast cancer. Neoadjuvant gemcitabine (1,000 mg/m(2) intravenously
      [IV] on days 1 and 8), carboplatin (area under curve of 2 IV on days 1 and 8),
      and iniparib (5.6 mg/kg IV on days 1, 4, 8, and 11) were administered every 21
      days for four cycles, until the protocol was amended to six cycles. The primary
      end point was pathologic complete response (no invasive carcinoma in breast or
      axilla). All patients underwent comprehensive BRCA1/2 genotyping, and homologous
      recombination deficiency was assessed by loss of heterozygosity (HRD-LOH) in
      pretreatment core breast biopsies. RESULTS: Among 80 patients, median age was 48
      years; 19 patients (24%) had germline BRCA1 or BRCA2 mutations; clinical stage
      was I (13%), IIA (36%), IIB (36%), and IIIA (15%). Overall pathologic complete
      response rate in the intent-to-treat population (n = 80) was 36% (90% CI, 27 to
      46). Mean HRD-LOH scores were higher in responders compared with nonresponders (P
      = .02) and remained significant when BRCA1/2 germline mutations carriers were
      excluded (P = .021). CONCLUSION: Preoperative combination of gemcitabine,
      carboplatin, and iniparib is active in the treatment of early-stage triple
      negative and BRCA1/2 mutation-associated breast cancer. The HRD-LOH assay was
      able to identify patients with sporadic triple-negative breast cancer lacking a
      BRCA1/2 mutation, but with an elevated HRD-LOH score, who achieved a favorable
      pathologic response. Confirmatory controlled trials are warranted.

PMID- 25847930
TI  - Outcomes of Patients With Chronic Lymphocytic Leukemia and Richter's
      Transformation After Transplantation Failure.
AB  - PURPOSE: Allogeneic stem-cell transplantation (SCT) induces long-term remission
      in a fraction of patients with high-risk chronic lymphocytic leukemia (CLL) or
      Richter's transformation (RT). Our purpose was to determine the outcomes of
      patients whose disease progressed after allogeneic SCT. PATIENTS AND METHODS: We
      retrospectively analyzed the outcomes of 72 patients (52 with CLL and 20 with RT)
      who underwent allogeneic SCT between 1998 and 2011 and had documented progression
      after transplantation. Twenty-two (31%) never had a response, and 50 (69%) had a
      response but experienced relapse after a median of 7 months (range, 2 to 85
      months). Forty-eight patients who were receiving or were candidates to receive
      post-SCT cell-based therapies were not included in this analysis. RESULTS: The
      median age at time of transplantation was 58 years (range, 30 to 72 years). Sixty
      two patients (86%) received more than two treatment regimens and 37 (51%)
      received more than three treatment regimens before SCT. Sixty-six patients (92%)
      had active disease at the time of transplantation. The 2- and 5-year survival
      rates were 67% and 38% (patients with CLL) and 36% and 0% (patients with RT). The
      patients who developed acute or chronic graft-versus-host disease had a longer
      overall survival (OS; P = .05). In a multivariable analysis, RT or low hemoglobin
      at the time of SCT predicted shorter OS. Chronic graft-versus-host disease and an
      initial response to SCT predicted longer OS. CONCLUSION: Patients with CLL in
      whom allogeneic SCT fails may have a response to and benefit from salvage
      therapies, and their prognosis is relatively good.

PMID- 25847931
TI  - Molecular profiling is rather likely to be cost effective.

PMID- 25847932
TI  - Reply to C.G. Rusthoven et al.

PMID- 25847933
TI  - Reply to V.P. Retel et al, D. Gauchan et al, and C. Rahilly-Tierney et al.

PMID- 25847935
TI  - Reply to C.G. Rusthoven et al.

PMID- 25847934
TI  - SWOG S0925: A Randomized Phase II Study of Androgen Deprivation Combined With
      Cixutumumab Versus Androgen Deprivation Alone in Patients With New Metastatic
      Hormone-Sensitive Prostate Cancer.
AB  - PURPOSE: Cixutumumab, formerly IMC-A12, is a recombinant human monoclonal
      immunoglobulin G1 antibody that targets insulin-like growth factor I receptor
      (IGF-IR). Cixutumumab was synergistic with castration in a hormone-sensitive
      prostate cancer xenograft model. PATIENTS AND METHODS: Patients with new
      metastatic prostate cancer were randomly assigned within 30 days of initiating
      androgen deprivation (AD) to cixutumumab added to a luteinizing hormone-releasing
      hormone agonist with bicalutamide versus AD alone. With 180 patients and one
      sided alpha of 0.10, there would be 90% power to detect an absolute 20%
      difference in undetectable prostate-specific antigen (PSA; <= 0.2 ng/mL) rate at
      28 weeks (relative risk, 1.44); this end point was previously strongly correlated
      with survival. Secondary end points included the proportion of patients with PSA
      > 4.0 ng/mL, safety and tolerability, circulating tumor cell (CTC) levels, and
      seven plasma IGF-IR biomarkers. Fisher's exact test was used for the primary end
      point, and extended Mantel-Haenszel chi(2) test was used for three PSA response
      categories. RESULTS: The trial accrued 210 eligible patients (105 randomly
      assigned to each arm). Patient characteristics were similar in both arms.
      Undetectable PSA rate was 42 (40.0%) of 105 for cixutumumab plus AD and 34
      (32.3%) of 105 for AD alone (relative risk, 1.24; one-sided P = .16). Lower
      baseline CTCs (0 v 1 to 4 v >= 5/7.5 mL whole blood) were associated with higher
      rate of PSA response (three categories; P = .036) in 39 evaluable patients. IGF
      IR biomarkers were not correlated with PSA outcome, and cixutumumab did not
      significantly change these biomarker levels. CONCLUSION: Cixutumumab plus AD did
      not significantly increase the undetectable PSA rate in men with new metastatic
      hormone-sensitive prostate cancer. CTCs at baseline may carry prognostic value.

PMID- 25847937
TI  - External Validation of the Benefit of Adjuvant Radiotherapy for Pathologic N1M0
      Prostate Cancer.

PMID- 25847936
TI  - TBCRC009: A Multicenter Phase II Clinical Trial of Platinum Monotherapy With
      Biomarker Assessment in Metastatic Triple-Negative Breast Cancer.
AB  - PURPOSE: The identification of patients with metastatic triple-negative breast
      cancer (mTNBC) who are expected to benefit from platinum-based chemotherapy is of
      interest. We conducted a single-arm phase II clinical trial of single-agent
      platinum for mTNBC with biomarker correlates. PATIENTS AND METHODS: Patients with
      mTNBC received first- or second-line cisplatin (75 mg/m(2)) or carboplatin (area
      under the concentration-time curve 6) by physician's choice once every 3 weeks.
      Coprimary end points were objective response rate (RR) and response prediction by
      p63/p73 gene expression. Secondary and exploratory end points included toxicity
      assessment, RR in cisplatin versus carboplatin, and RR in molecularly defined
      subgroups, including BRCA1/2 mutation carriers. RESULTS: Patients (N = 86; 69 as
      first-line therapy) received cisplatin (n = 43) or carboplatin (n = 43). RR was
      25.6% (95% CI, 16.8% to 36%) and was numerically higher with cisplatin (32.6%)
      than with carboplatin (18.7%). RR was 54.5% in patients with germline BRCA1/2
      mutations (n = 11). In patients without BRCA1/2 mutations (n = 66), exploratory
      analyses showed that a BRCA-like genomic instability signature (n = 32)
      discriminated responding and nonresponding tumors (mean homologous recombination
      deficiency-loss of heterozygosity/homologous recombination deficiency-large-scale
      state transitions [HRD-LOH/HRD-LST] scores were 12.68 and 5.11, respectively),
      whereas predefined analysis by p63/p73 expression status (n = 61), p53 and PIK3CA
      mutation status (n = 53), or PAM50 gene expression subtype (n = 55) did not. Five
      of the six long-term responders alive at a median of 4.5 years lacked germline
      BRCA1/2 mutations, and two of them had increased tumor HRD-LOH/HRD-LST scores.
      CONCLUSION: Platinum agents are active in mTNBC, especially in patients with
      germline BRCA1/2 mutations. A measure of tumor DNA repair function may identify
      patients without mutations who could benefit from platinum therapy agents.
      Prospective controlled confirmatory trials are warranted.

PMID- 25847938
TI  - Cost-effectiveness of the 70-gene signature versus adjuvant! Online and
      systematic chemotherapy for risk stratification of patients with node-negative
      breast cancer: does accuracy matter?

PMID- 25847939
TI  - Cost-effectiveness of molecular profiling for early breast cancer.

PMID- 25847940
TI  - Concerns about cancer risk and experiences with genetic testing in a diverse
      population of patients with breast cancer.
AB  - PURPOSE: To evaluate preferences for and experiences with genetic testing in a
      diverse cohort of patients with breast cancer identified through population-based
      registries, with attention to differences by race/ethnicity. METHODS: We surveyed
      women diagnosed with nonmetastatic breast cancer from 2005 to 2007, as reported
      to the SEER registries of metropolitan Los Angeles and Detroit, about experiences
      with hereditary risk evaluation. Multivariable models evaluated correlates of a
      strong desire for genetic testing, unmet need for discussion with a health care
      professional, and receipt of testing. RESULTS: Among 1,536 patients who completed
      the survey, 35% expressed strong desire for genetic testing, 28% reported
      discussing testing with a health care professional, and 19% reported test
      receipt. Strong desire for testing was more common in younger women, Latinas, and
      those with family history. Minority patients were significantly more likely to
      have unmet need for discussion (failure to discuss genetic testing with a health
      professional when they had a strong desire for testing): odds ratios of 1.68,
      2.44, and 7.39 for blacks, English-speaking Latinas, and Spanish-speaking Latinas
      compared with whites, respectively. Worry in the long-term survivorship period
      was higher among those with unmet need for discussion (48.7% v 24.9%; P <.001).
      Patients who received genetic testing were younger, less likely to be black, and
      more likely to have a family cancer history. CONCLUSION: Many patients,
      especially minorities, express a strong desire for genetic testing and may
      benefit from discussion to clarify risks. Clinicians should discuss genetic risk
      even with patients they perceive to be at low risk, as this may reduce worry.

PMID- 25847941
TI  - EMERGE: A Randomized Phase II Study of the Antibody-Drug Conjugate Glembatumumab
      Vedotin in Advanced Glycoprotein NMB-Expressing Breast Cancer.
AB  - PURPOSE: Glycoprotein NMB (gpNMB), a negative prognostic marker, is overexpressed
      in multiple tumor types. Glembatumumab vedotin is a gpNMB-specific monoclonal
      antibody conjugated to the potent cytotoxin monomethyl auristatin E. This phase
      II study investigated the activity of glembatumumab vedotin in advanced breast
      cancer by gpNMB expression. PATIENTS AND METHODS: Patients (n = 124) with
      refractory breast cancer that expressed gpNMB in >= 5% of epithelial or stromal
      cells by central immunohistochemistry were stratified by gpNMB expression (tumor,
      low stromal intensity, high stromal intensity) and were randomly assigned 2:1 to
      glembatumumab vedotin (n = 83) or investigator's choice (IC) chemotherapy (n =
      41). The study was powered to detect overall objective response rate (ORR) in the
      glembatumumab vedotin arm between 10% (null) and 22.5% (alternative hypothesis)
      with preplanned investigation of activity by gpNMB distribution and/or intensity
      (Stratum 1 to Stratum 3). RESULTS: Glembatumumab vedotin was well tolerated as
      compared with IC chemotherapy (less hematologic toxicity; more rash, pruritus,
      neuropathy, and alopecia). ORR was 6% (five of 83) for glembatumumab vedotin
      versus 7% (three of 41) for IC, without significant intertreatment differences
      for predefined strata. Secondary end point revealed ORR of 12% (10 of 83) versus
      12% (five of 41) overall, and 30% (seven of 23) versus 9% (one of 11) for gpNMB
      overexpression (>= 25% of tumor cells). Unplanned analysis showed ORR of 18%
      (five of 28) versus 0% (0 of 11) in patients with triple-negative breast cancer
      (TNBC), and 40% (four of 10) versus 0% (zero of six) in gpNMB-overexpressing
      TNBC. CONCLUSION: Glembatumumab vedotin is well tolerated in heavily pretreated
      patients with breast cancer. Although the primary end point in advanced gpNMB
      expressing breast cancer was not met for all enrolled patients (median tumor
      gpNMB expression, 5%), activity may be enhanced in patients with gpNMB
      overexpressing tumors and/or TNBC. A pivotal phase II trial (METRIC [Metastatic
      Triple-Negative Breast Cancer]) is underway.

PMID- 25847945
TI  - Transcellular delivery of vesicular SOCS proteins from macrophages to epithelial
      cells blunts inflammatory signaling.
AB  - JAK-STAT signaling mediates the actions of numerous cytokines and growth factors,
      and its endogenous brake is the family of SOCS proteins. Consistent with their
      intracellular roles, SOCS proteins have never been identified in the
      extracellular space. Here we report that alveolar macrophages can secrete SOCS1
      and -3 in exosomes and microparticles, respectively, for uptake by alveolar
      epithelial cells and subsequent inhibition of STAT activation. Secretion is
      tunable and occurs both in vitro and in vivo. SOCS secretion into lung lining
      fluid was diminished by cigarette smoking in humans and mice. Secretion and
      transcellular delivery of vesicular SOCS proteins thus represent a new model for
      the control of inflammatory signaling, which is subject to dysregulation during
      states of inflammation.

PMID- 25847946
TI  - An anti-silencer- and SATB1-dependent chromatin hub regulates Rag1 and Rag2 gene
      expression during thymocyte development.
AB  - Rag1 and Rag2 gene expression in CD4(+)CD8(+) double-positive (DP) thymocytes
      depends on the activity of a distant anti-silencer element (ASE) that counteracts
      the activity of an intergenic silencer. However, the mechanistic basis for ASE
      activity is unknown. Here, we show that the ASE physically interacts with the
      distant Rag1 and Rag2 gene promoters in DP thymocytes, bringing the two promoters
      together to form an active chromatin hub. Moreover, we show that the ASE
      functions as a classical enhancer that can potently activate these promoters in
      the absence of the silencer or other locus elements. In thymocytes lacking the
      chromatin organizer SATB1, we identified a partial defect in Tcra gene
      rearrangement that was associated with reduced expression of Rag1 and Rag2 at the
      DP stage. SATB1 binds to the ASE and Rag promoters, facilitating inclusion of
      Rag2 in the chromatin hub and the loading of RNA polymerase II to both the Rag1
      and Rag2 promoters. Our results provide a novel framework for understanding ASE
      function and demonstrate a novel role for SATB1 as a regulator of Rag locus
      organization and gene expression in DP thymocytes.

PMID- 25847947
TI  - DUSP4 deficiency caused by promoter hypermethylation drives JNK signaling and
      tumor cell survival in diffuse large B cell lymphoma.
AB  - The epigenetic dysregulation of tumor suppressor genes is an important driver of
      human carcinogenesis. We have combined genome-wide DNA methylation analyses and
      gene expression profiling after pharmacological DNA demethylation with functional
      screening to identify novel tumor suppressors in diffuse large B cell lymphoma
      (DLBCL). We find that a CpG island in the promoter of the dual-specificity
      phosphatase DUSP4 is aberrantly methylated in nodal and extranodal DLBCL,
      irrespective of ABC or GCB subtype, resulting in loss of DUSP4 expression in 75%
      of >200 examined cases. The DUSP4 genomic locus is further deleted in up to 13%
      of aggressive B cell lymphomas, and the lack of DUSP4 is a negative prognostic
      factor in three independent cohorts of DLBCL patients. Ectopic expression of wild
      type DUSP4, but not of a phosphatase-deficient mutant, dephosphorylates c-JUN N
      terminal kinase (JNK) and induces apoptosis in DLBCL cells. Pharmacological or
      dominant-negative JNK inhibition restricts DLBCL survival in vitro and in vivo
      and synergizes strongly with the Bruton's tyrosine kinase inhibitor ibrutinib.
      Our results indicate that DLBCL cells depend on JNK signaling for survival. This
      finding provides a mechanistic basis for the clinical development of JNK
      inhibitors in DLBCL, ideally in synthetic lethal combinations with inhibitors of
      chronic active B cell receptor signaling. 

PMID- 25847948
TI  - Hypoxia-independent upregulation of placental hypoxia inducible factor-1alpha
      gene expression contributes to the pathogenesis of preeclampsia.
AB  - Accumulation of hypoxia inducible factor-1alpha (HIF-1alpha) is commonly an acute
      and beneficial response to hypoxia, whereas chronically elevated HIF-1alpha is
      associated with multiple disease conditions, including preeclampsia, a serious
      hypertensive disease of pregnancy. However, the molecular basis underlying the
      persistent elevation of placental HIF-1alpha in preeclampsia and its role in the
      pathogenesis of preeclampsia are poorly understood. Here we report that Hif
      1alpha mRNA and HIF-1alpha protein were elevated in the placentas of pregnant
      mice infused with angiotensin II type I receptor agonistic autoantibody, a
      pathogenic factor in preeclampsia. Knockdown of placental Hif-1alpha mRNA by
      specific siRNA significantly attenuated hallmark features of preeclampsia induced
      by angiotensin II type I receptor agonistic autoantibody in pregnant mice,
      including hypertension, proteinuria, kidney damage, impaired placental
      vasculature, and elevated maternal circulating soluble fms-like tyrosine kinase-1
      levels. Next, we discovered that Hif-1alpha mRNA levels and HIF-1alpha protein
      levels were induced in an independent preeclampsia model with infusion of the
      inflammatory cytokine tumor necrosis factor superfamily member 14 (LIGHT). SiRNA
      knockdown experiments also demonstrated that elevated HIF-1alpha contributed to
      LIGHT-induced preeclampsia features. Translational studies with human placentas
      showed that angiotensin II type I receptor agonistic autoantibody or LIGHT is
      capable of inducing HIF-1alpha in a hypoxia-independent manner. Moreover,
      increased HIF-1alpha was found to be responsible for angiotensin II type I
      receptor agonistic autoantibody or LIGHT-induced elevation of Flt-1 gene
      expression and production of soluble fms-like tyrosine kinase-1 in human villous
      explants. Overall, we demonstrated that hypoxia-independent stimulation of HIF
      1alpha gene expression in the placenta is a common pathogenic mechanism promoting
      disease progression. Our findings reveal new insight to preeclampsia and
      highlight novel therapeutic possibilities for the disease.

PMID- 25847949
TI  - Regulatory T cells ameliorate intrauterine growth retardation in a transgenic rat
      model for preeclampsia.
AB  - Preeclampsia is a multisystemic syndrome during pregnancy that is often
      associated with intrauterine growth retardation. Immunologic dysregulation,
      involving T cells, is implicated in the pathogenesis. The aim of this study was
      to evaluate the effect of upregulating regulatory T cells in an established
      transgenic rat model for preeclampsia. Application of superagonistic monoclonal
      antibody for CD28 has been shown to effectively upregulate regulatory T cells. In
      the first protocol (treatment protocol), we applied 1 mg of CD28 superagonist or
      control antibody on days 11 and 15 of pregnancy. In the second protocol
      (prevention protocol), the superagonist or control antibody was applied on days
      1, 5, and 9. Superagonist increased regulatory T cells in circulation and
      placenta from 8.49+/-2.09% of CD4-positive T cells to 23.50+/-3.05% and from
      3.85+/-1.45% to 23.27+/-7.64%, respectively. Blood pressure and albuminuria
      (30.6+/-15.1 versus 14.6+/-5.5 mg/d) were similar in the superagonist or control
      antibody-treated preeclamptic group for both protocols. Rats treated with CD28
      superagonist showed increased pup weights in the prevention protocol (2.66+/-0.03
      versus 2.37+/-0.05 g) and in the treatment protocol (3.04+/-0.04 versus 2.54+/
      0.1 g). Intrauterine growth retardation, calculated by brain:liver weight ratio,
      was also decreased by the superagonist in both protocols. Further analysis of
      brain development revealed a 20% increase in brain volume by the superagonist.
      Induction of regulatory T cells in the circulation and the uteroplacental unit in
      an established preeclamptic rat model had no influence on maternal hypertension
      and proteinuria. However, it substantially improved fetal outcome by ameliorating
      intrauterine growth retardation.

PMID- 25847950
TI  - Incident atrial fibrillation hazard in hypertensive population: a risk function
      from and for clinical practice.
AB  - Determining the risk of atrial fibrillation within the hypertensive population
      without ischemic vascular disease would aid in decision making on preventive
      approaches. Accordingly, we aimed to estimate the risk of incident atrial
      fibrillation in this population. We conducted an historical cohort study between
      July 1, 2006, and December 31, 2011, using anonymized longitudinal patient
      information from primary care and hospital discharge records contained in the
      System for the Development of Research in Primary Care database. We included 255
      440 hypertensive patients, aged >=55 years at the time of study entry.
      Individuals with previous atrial fibrillation, ischemic heart disease, stroke,
      and peripheral artery disease were excluded. To build the incident atrial
      fibrillation risk function, a derivation and a validation cohort were defined,
      representing 60% and 40% of the entire database, respectively, and a Cox
      proportional hazards model was fitted. Atrial fibrillation incidence was 7.24 per
      1000 person-years (95% confidence interval, 7.08-7.40). The final model included
      age, weight, total cholesterol, heart failure, valvular heart disease, and
      antihypertensive treatment. Its concordance index (standard error) was 0.769
      (0.004) and 0.768 (0.005) in the derivation and validation datasets,
      respectively. This research provides a tool, built with variables from daily
      clinical practice, that can be readily used in the primary care setting to
      predict atrial fibrillation incidence in the hypertensive population without
      ischemic vascular disease. The tool may help tailor individualized diagnostic and
      preventive care decisions.

PMID- 25847954
TI  - Old Habits Die Hard: Addiction of BRAF-Mutant Cancer Cells to MAP Kinase
      Signaling.
AB  - Dual and triple combination therapies with RAF inhibitors plus other targeted
      agents have demonstrated promising clinical utility in BRAFV600-mutant solid
      tumors. However, despite vertical inhibition at multiple nodes on the MAPK
      signaling pathway, resistant tumors emerge. Ahronian and colleagues show that in
      BRAF-mutant colorectal cancer, resistance involves reactivation of
      RAS/RAF/MEK/ERK signaling and may be overcome by newly emerging ERK inhibitors.

PMID- 25847955
TI  - miRSNP-Based Approach Identifies a miRNA That Regulates Prostate-Specific Antigen
      in an Allele-Specific Manner.
AB  - A recent study identified genetic variations within the miRNA response elements
      of miRNA target genes (miRSNP) that can affect the base paring between miRNAs and
      their targets, and hence alter miRNA-target interactions. The authors also
      undertook functional validation studies and were able to demonstrate that
      overexpression of miR-3162-5p resulted in a 20% decrease in expression of the
      KLK3 rs1058205 SNP T-allele.

PMID- 25847956
TI  - Targeting Autophagy in BRAF-Mutant Tumors.
AB  - Recent studies have highlighted the opportunity to treat cancer by inhibiting
      autophagy, but have also raised important caveats with this idea. An article in
      this issue of Cancer Discovery adds to accumulating evidence suggesting that we
      should focus our efforts (at least initially) on specific tumors where we are
      most likely to see beneficial effects.

PMID- 25847957
TI  - Paralog-Specific Kinase Inhibition of FGFR4: Adding to the Arsenal of Anti-FGFR
      Agents.
AB  - In this issue of Cancer Discovery, Hagel and colleagues report the design and the
      in vitro and in vivo activity of a novel, irreversible, paralog-specific kinase
      inhibitor of FGFR4, BLU9931. This compound binds covalently to a cysteine residue
      in the hinge region of FGFR4 but not in FGFR1-3. BLU9931 induces tumor shrinkage
      in hepatocellular carcinoma models that express a functioning ligand/receptor
      complex consisting of FGF19/FGFR4/KLB and adds to a growing list of anti-FGFR4
      agents.

PMID- 25847958
TI  - Selective requirement of the shikimate pathway of Legionella pneumophila for
      intravacuolar growth within human macrophages but not within Acanthamoeba.
AB  - Legionella pneumophila utilizes the Dot/Icm type IV translocation system to
      proliferate within a vacuole in a wide variety of natural amoebal hosts and in
      alveolar macrophages of the human accidental host. Although L. pneumophila
      utilizes host amino acids as the main sources of carbon and energy, it is not
      known whether de novo synthesis of amino acids by intravacuolar L. pneumophila
      contributes to its nutrition. The aroB and aroE genes encode enzymes for the
      shikimate pathway that generates the aromatic amino acids Phe, Trp, and Tyr. Here
      we show the aroB and aroE mutants of L. pneumophila to be defective in growth in
      human monocyte-derived macrophages (hMDMs) but not in Acanthamoeba spp. The aroB
      and aroE mutants are severely attenuated in intrapulmonary proliferation in the
      A/J mouse model of Legionnaires' disease, and the defect is fully complemented by
      the respective wild-type alleles. The two mutants grow normally in rich media but
      do not grow in defined media lacking aromatic amino acids, and the growth defect
      is rescued by inclusion of the aromatic amino acids, which are essential for
      production of the pyomelanin pigment. Interestingly, supplementation of infected
      hMDMs with the three aromatic amino acids or with Trp alone rescues the
      intramacrophage defect of the aroE but not the aroB mutant. Therefore, the
      shikimate pathway of L. pneumophila is differentially required for optimal growth
      within human macrophages, which are auxotrophic for Trp and Phe, but is
      dispensable for growth within the Acanthamoeba spp. that synthesize the aromatic
      amino acids.

PMID- 25847960
TI  - Staphylococcus aureus induces hypoxia and cellular damage in porcine dermal
      explants.
AB  - We developed a porcine dermal explant model to determine the extent to which
      Staphylococcus aureus biofilm communities deplete oxygen, change pH, and produce
      damage in underlying tissue. Microelectrode measurements demonstrated that
      dissolved oxygen (DO) in biofilm-free dermal tissue was 4.45 +/- 1.17 mg/liter,
      while DO levels for biofilm-infected tissue declined sharply from the surface,
      with no measurable oxygen detectable in the underlying dermal tissue. Magnetic
      resonance imaging demonstrated that biofilm-free dermal tissue had a
      significantly lower relative effective diffusion coefficient (0.26 +/- 0.09 to
      0.30 +/- 0.12) than biofilm-infected dermal tissue (0.40 +/- 0.12 to 0.48 +/-
      0.12; P < 0.0001). Thus, the difference in DO level was attributable to biofilm
      induced oxygen demand rather than changes in oxygen diffusivity. Microelectrode
      measures showed that pH within biofilm-infected explants was more alkaline than
      in biofilm-free explants (8.0 +/- 0.17 versus 7.5 +/- 0.15, respectively; P <
      0.002). Cellular and nuclear details were lost in the infected explants,
      consistent with cell death. Quantitative label-free shotgun proteomics
      demonstrated that both proapoptotic programmed cell death protein 5 and
      antiapoptotic macrophage migration inhibitory factor accumulated in the infected
      explant spent medium, compared with uninfected-explant spent media (1,351-fold
      and 58-fold, respectively), consistent with the cooccurrence of apoptosis and
      necrosis in the explants. Biofilm-origin proteins reflected an extracellular
      matrix-adapted lifestyle of S. aureus. S. aureus biofilms deplete oxygen,
      increase pH, and induce cell death, all factors that contribute to impede wound
      healing.

PMID- 25847959
TI  - Mechanisms of inflammasome activation by Vibrio cholerae secreted toxins vary
      with strain biotype.
AB  - Activation of inflammasomes is an important aspect of innate immune responses to
      bacterial infection. Recent studies have linked Vibrio cholerae secreted toxins
      to inflammasome activation by using murine macrophages. To increase relevance to
      human infection, studies of inflammasome-dependent cytokine secretion were
      conducted with the human THP-1 monocytic cell line and corroborated in primary
      human peripheral blood mononuclear cells (PBMCs). Both El Tor and classical
      strains of V. cholerae activated ASC (apoptosis-associated speck-like protein
      containing a CARD domain)-dependent release of interleukin-1beta (IL-1beta) when
      cultured with human THP-1 cells, but the pattern of induction was distinct,
      depending on the repertoire of toxins the strains produced. El Tor biotype
      strains induced release of IL-1beta dependent on NOD-like receptor family pyrin
      domain-containing 3 (NLRP3) and ASC due to the secreted pore-forming toxin
      hemolysin. Unlike in studies with mouse macrophages, the MARTX toxin did not
      contribute to IL-1beta release from human monocytic cells. Classical biotype
      strains, which do not produce either hemolysin or the MARTX toxin, activated low
      level IL-1beta release that was induced by cholera toxin (CT) and dependent on
      ASC but independent of NLRP3 and pyroptosis. El Tor strains likewise showed
      increased IL-1beta production dependent on CT when the hemolysin gene was
      deleted. In contrast to studies with murine macrophages, this phenotype was
      dependent on a catalytically active CT A subunit capable of inducing production
      of cyclic AMP and not on the B subunit. These studies demonstrate that the
      induction of the inflammasome in human THP-1 monocytes and in PBMCs by V.
      cholerae varies with the biotype and is mediated by both NLRP3-dependent and 
      independent pathways.

PMID- 25847961
TI  - Transcriptional analysis of the MrpJ network: modulation of diverse virulence
      associated genes and direct regulation of mrp fimbrial and flhDC flagellar
      operons in Proteus mirabilis.
AB  - The enteric bacterium Proteus mirabilis is associated with a significant number
      of catheter-associated urinary tract infections (UTIs). Strict regulation of the
      antagonistic processes of adhesion and motility, mediated by fimbriae and
      flagella, respectively, is essential for disease progression. Previously, the
      transcriptional regulator MrpJ, which is encoded by the mrp fimbrial operon, has
      been shown to repress both swimming and swarming motility. Here we show that MrpJ
      affects an array of cellular processes beyond adherence and motility. Microarray
      analysis found that expression of mrpJ mimicking levels observed during UTIs
      leads to differential expression of 217 genes related to, among other functions,
      bacterial virulence, type VI secretion, and metabolism. We probed the molecular
      mechanism of transcriptional regulation by MrpJ using transcriptional reporters
      and chromatin immunoprecipitation (ChIP). Binding of MrpJ to two virulence
      associated target gene promoters, the promoters of the flagellar master regulator
      flhDC and mrp itself, appears to be affected by the condensation state of the
      native chromosome, although both targets share a direct MrpJ binding site
      proximal to the transcriptional start. Furthermore, an mrpJ deletion mutant
      colonized the bladders of mice at significantly lower levels in a transurethral
      model of infection. Additionally, we observed that mrpJ is widely conserved in a
      collection of recent clinical isolates. Altogether, these findings support a role
      of MrpJ as a global regulator of P. mirabilis virulence.

PMID- 25847962
TI  - Inactivation of the antifungal and immunomodulatory properties of human
      cathelicidin LL-37 by aspartic proteases produced by the pathogenic yeast Candida
      albicans.
AB  - Constant cross talk between Candida albicans yeast cells and their human host
      determines the outcome of fungal colonization and, eventually, the progress of
      infectious disease (candidiasis). An effective weapon used by C. albicans to cope
      with the host defense system is the release of 10 distinct secreted aspartic
      proteases (SAPs). Here, we validate a hypothesis that neutrophils and epithelial
      cells use the antimicrobial peptide LL-37 to inactivate C. albicans at sites of
      candidal infection and that C. albicans uses SAPs to effectively degrade LL-37.
      LL-37 is cleaved into multiple products by SAP1 to -4, SAP8, and SAP9, and this
      proteolytic processing is correlated with the gradual decrease in the antifungal
      activity of LL-37. Moreover, a major intermediate of LL-37 cleavage-the LL-25
      peptide-is antifungal but devoid of the immunomodulatory properties of LL-37. In
      contrast to LL-37, LL-25 did not affect the generation of reactive oxygen species
      by neutrophils upon treatment with phorbol esters. Stimulating neutrophils with
      LL-25 (rather than LL-37) significantly decreased calcium flux and interleukin-8
      production, resulting in lower chemotactic activity of the peptide against
      neutrophils, which may decrease the recruitment of neutrophils to infection foci.
      LL-25 also lost the function of LL-37 as an inhibitor of neutrophil apoptosis,
      thereby reducing the life span of these defense cells. This study indicates that
      C. albicans can effectively use aspartic proteases to destroy the antimicrobial
      and immunomodulatory properties of LL-37, thus enabling the pathogen to survive
      and propagate.

PMID- 25847963
TI  - Air pollution particulate matter alters antimycobacterial respiratory epithelium
      innate immunity.
AB  - Inhalation exposure to indoor air pollutants and cigarette smoke increases the
      risk of developing tuberculosis (TB). Whether exposure to ambient air pollution
      particulate matter (PM) alters protective human host immune responses against
      Mycobacterium tuberculosis has been little studied. Here, we examined the effect
      of PM from Iztapalapa, a municipality of Mexico City, with aerodynamic diameters
      below 2.5 MUm (PM2.5) and 10 MUm (PM10) on innate antimycobacterial immune
      responses in human alveolar type II epithelial cells of the A549 cell line.
      Exposure to PM2.5 or PM10 deregulated the ability of the A549 cells to express
      the antimicrobial peptides human beta-defensin 2 (HBD-2) and HBD-3 upon infection
      with M. tuberculosis and increased intracellular M. tuberculosis growth (as
      measured by CFU count). The observed modulation of antibacterial responsiveness
      by PM exposure was associated with the induction of senescence in PM-exposed A549
      cells and was unrelated to PM-mediated loss of cell viability. Thus, the
      induction of senescence and downregulation of HBD-2 and HBD-3 expression in
      respiratory PM-exposed epithelial cells leading to enhanced M. tuberculosis
      growth represent mechanisms by which exposure to air pollution PM may increase
      the risk of M. tuberculosis infection and the development of TB.

PMID- 25847964
TI  - AMA1-deficient Toxoplasma gondii parasites transiently colonize mice and trigger
      an innate immune response that leads to long-lasting protective immunity.
AB  - The apical membrane antigen 1 (AMA1) protein was believed to be essential for the
      perpetuation of two Apicomplexa parasite genera, Plasmodium and Toxoplasma, until
      we genetically engineered viable parasites lacking AMA1. The reduction in
      invasiveness of the Toxoplasma gondii RH-AMA1 knockout (RH-AMA1(KO)) tachyzoite
      population, in vitro, raised key questions about the outcome associated with
      these tachyzoites once inoculated in the peritoneal cavity of mice. In this
      study, we used AMNIS technology to simultaneously quantify and image the
      parasitic process driven by AMA1(KO) tachyzoites. We report their ability to
      colonize and multiply in mesothelial cells and in both resident and recruited
      leukocytes. While the RH-AMA1(KO) population amplification is rapidly lethal in
      immunocompromised mice, it is controlled in immunocompetent hosts, where immune
      cells in combination sense parasites and secrete proinflammatory cytokines. This
      innate response further leads to a long-lasting status immunoprotective against a
      secondary challenge by high inocula of the homologous type I or a distinct type
      II T. gondii genotypes. While AMA1 is definitively not an essential protein for
      tachyzoite entry and multiplication in host cells, it clearly assists the
      expansion of parasite population in vivo.

PMID- 25847965
TI  - Pneumoperitoneum as a valuable option in the treatment of post lower lobectomy
      bronchopleural fistula.
AB  - Although the incidence of post-lobectomy bronchopleural fistula has decreased
      over years, it remains a threatening complication in lung surgery. Once the
      fistula is diagnosed, treatment options are several. Conservative versus
      operative treatment is currently a matter of debate generally regarding timing,
      patient's condition and fistula's size. Although prompt resurgery is strongly
      suggested for early onset large fistulas, the clinical scenario may suggest a
      cautious conduct and conservative treatment could be advocated and repeated.
      Endoscopic management is now widely employed for limited, small bronchial
      dehiscence while pneumoperitoneum has surprisingly never been reported for this
      purpose, despite its potential. We report a case of a complete right lower lobe
      bronchial stump reopening, successfully treated by pneumoperitoneum. 

PMID- 25847966
TI  - Development of an algorithm to plan and simulate a new interventional procedure.
AB  - OBJECTIVES: The number of implanted biological valves for treatment of valvular
      heart disease is growing and a percentage of these patients will eventually
      undergo a transcatheter valve-in-valve (ViV) procedure. Some of these patients
      will represent challenging cases. The aim of this study was to develop a feasible
      algorithm to plan and in vitro simulate a new interventional procedure to improve
      patient outcome. METHODS: In addition to standard diagnostic routine, our
      algorithm includes 3D printing of the annulus, hydrodynamic measurements and high
      speed analysis of leaflet kinematics after simulation of the procedure in
      different prosthesis positions as well as X-ray imaging of the most suitable
      valve position to create a 'blueprint' for the patient procedure. RESULTS: This
      algorithm was developed for a patient with a degenerated Perceval aortic
      sutureless prosthesis requiring a ViV procedure. Different ViV procedures were
      assessed in the algorithm and based on these results the best option for the
      patient was chosen. The actual procedure went exactly as planned with help of
      this algorithm. CONCLUSIONS: Here we have developed a new technically feasible
      algorithm simulating important aspects of a novel interventional procedure prior
      to the actual procedure. This algorithm can be applied to virtually all patients
      requiring a novel interventional procedure to help identify risks and find
      optimal parameters for prosthesis selection and placement in order to maximize
      safety for the patient.

PMID- 25847969
TI  - A Sensory 3D Map of the Odor Description Space Derived from a Comparison of
      Numeric Odor Profile Databases.
AB  - Many authors have proposed different schemes of odor classification, which are
      useful to aid the complex task of describing smells. However, reaching a
      consensus on a particular classification seems difficult because our
      psychophysical space of odor description is a continuum and is not clustered into
      well-defined categories. An alternative approach is to describe the perceptual
      space of odors as a low-dimensional coordinate system. This idea was first
      proposed by Crocker and Henderson in 1927, who suggested using numeric profiles
      based on 4 dimensions: "fragrant," "acid," "burnt," and "caprylic." In the
      present work, the odor profiles of 144 aroma chemicals were compared by means of
      statistical regression with comparable numeric odor profiles obtained from 2
      databases, enabling a plausible interpretation of the 4 dimensions. Based on the
      results and taking into account comparable 2D sensory maps of odor descriptors
      from the literature, a 3D sensory map (odor cube) has been drawn up to improve
      understanding of the similarities and dissimilarities of the odor descriptors
      most frequently used in fragrance chemistry. 

PMID- 25847967
TI  - alphabeta TCR-mediated recognition: relevance to tumor-antigen discovery and
      cancer immunotherapy.
AB  - alphabeta T lymphocytes sense perturbations in host cellular body components
      induced by infectious pathogens, oncogenic transformation, or chemical or
      physical damage. Millions to billions of these lymphocytes are generated through
      T-lineage development in the thymus, each endowed with a clonally restricted
      surface T-cell receptor (TCR). An individual TCR has the capacity to recognize a
      distinct "foreign" peptide among the myriad of antigens that the mammalian host
      must be capable of detecting. TCRs explicitly distinguish foreign from self
      peptides bound to major histocompatibility complex (MHC) molecules. This is a
      daunting challenge, given that the MHC-linked peptidome consists of thousands of
      distinct peptides with a relevant nonself target antigen often embedded at low
      number, among orders of magnitude higher frequency self-peptides. In this Masters
      of Immunology article, I review how TCR structure and attendant mechanobiology
      involving nonlinear responses affect sensitivity as well as specificity to meet
      this requirement. Assessment of human tumor-cell display using state-of-the-art
      mass spectrometry physical detection methods that quantify epitope copy number
      can help to provide information about requisite T-cell functional avidity
      affording protection and/or therapeutic immunity. Future rational CD8 cytotoxic T
      cell-based vaccines may follow, targeting virally induced cancers, other nonviral
      immunogenic tumors, and potentially even nonimmunogenic tumors whose peptide
      display can be purposely altered by MHC-binding drugs to stimulate immune attack.

PMID- 25847968
TI  - The emerging understanding of myeloid cells as partners and targets in tumor
      rejection.
AB  - Myeloid cells are the most prominent among cells capable of presenting tumor
      derived antigens to T cells and thereby maintaining the latter in an activated
      state. Myeloid populations of the tumor microenvironment prominently include
      monocytes and neutrophils (sometimes loosely grouped as myeloid-derived
      suppressor cells), macrophages, and dendritic cells. Although intratumoral
      myeloid populations, as a whole, have long been considered nonstimulatory or
      suppressive, it has only recently been appreciated that not all tumor
      infiltrating myeloid cells are made equal. Because of advances in high
      dimensional flow cytometry as well as more robust transcriptional profiling, we
      now also understand that the subsets of the tumor-myeloid compartment are far
      more diverse and notably even contain a rare population of stimulatory dendritic
      cells. As all of these myeloid populations represent major T-cell-interacting
      partners for incoming tumor-reactive cytotoxic T lymphocytes, understanding the
      distinctions in their lineage and function reveals and guides numerous
      therapeutic avenues targeting these antigen-presenting cells. In this Cancer
      Immunology at the Crossroads overview, we review the recent progress in this
      rapidly evolving field and advance the hypothesis that the antigen-presenting
      compartment within tumor microenvironments may contain significant numbers of
      potent allies to be leveraged for immune-based tumor clearance.

PMID- 25847970
TI  - Monocyte phenotypes: when local education counts.

PMID- 25847971
TI  - Breaking the allergic response by disrupting antibody glycosylation.

PMID- 25847972
TI  - MAVS Promotes Inflammasome Activation by Targeting ASC for K63-Linked
      Ubiquitination via the E3 Ligase TRAF3.
AB  - Stringent control of inflammasome signaling pathway is important for maintaining
      immunological balance, yet the molecular mechanisms responsible for its tight
      regulation are still poorly understood. In this study, we found that the
      signaling pathway dependent on mitochondrial antiviral signaling protein (MAVS)
      was required for the optimal activation of apoptosis-associated specklike protein
      (ASC)-dependent inflammasome. In particular, TNFR-associated factor 3 was found
      to be a direct E3 ligase for ASC. Ubiquitination of ASC at Lys(174) was critical
      for speck formation and inflammasome activation. Deficiency in MAVS or TNFR
      associated factor 3 impaired ASC ubiquitination and cytosolic aggregates
      formation, resulting in reduced inflammasome response upon RNA virus infection.
      This study has identified a previously unrecognized role of MAVS in the
      regulation of inflammasome signaling and provided molecular insight into the
      mechanisms by which ubiquitination of ASC controls inflammasome activity through
      the formation of ASC specks. 

PMID- 25847973
TI  - IL-33 Enhances Host Tolerance to Candida albicans Kidney Infections through
      Induction of IL-13 Production by CD4+ T Cells.
AB  - Susceptibility to systemic Candida albicans infection is determined by immune
      resistance, as well as by the ability to control Candida-induced
      immunopathologies. We showed previously that exogenous IL-33 can increase
      resistance to peritoneal C. albicans infection by regulating multiple steps of
      the neutrophil anti-Candida response. In this study, using a mouse model of
      systemic candidiasis, we observed that IL-33 administration limited fungal burden
      and inflammation and increased survival. In kidneys, IL-33 seemed to directly act
      on neutrophils and CD4(+) T cells: IL-33 administration enhanced fungal clearance
      by increasing neutrophil phagocytic activity without which Candida proliferation
      was uncontrollable. In contrast, IL-33 stimulated CD4(+) T cells to produce IL
      13, which, in turn, drove the polarization of macrophages toward the M2 type.
      Furthermore, the absence of IL-13 abolished IL-33-mediated polarization of M2
      macrophages and renal functional recovery. In addition, IL-33 and IL-13 acted
      synergistically to increase M2 macrophage polarization and its phagocytic
      activity. Overall, this study identifies IL-33 as a cytokine that is able to
      induce resistance and tolerance and suggests that targeting resistance and
      tolerance simultaneously with therapeutic IL-33 may benefit patients with
      systemic candidiasis. 

PMID- 25847974
TI  - EBV oncogene N-LMP1 induces CD4 T cell-mediated angiogenic blockade in the murine
      tumor model.
AB  - Antivascular immunity may provide long-term protection by preventing
      neovascularization that precedes tumor progression. Although the tumorigenesis
      promoted by EBV-encoded oncogene latent membrane protein 1 derived from Taiwanese
      nasopharyngeal carcinoma (N-LMP1) has been demonstrated, the potential of N-LMP1
      for inducing immune surveillance remains elusive. In this article, we describe
      the immunogenicity of N-LMP1 (1510) and its induction of antivascular immunity in
      a transplantable tumor model in immunocompetent BALB/c mice. The immunogenicity
      of N-LMP1 was evaluated on the basis of tumor rejection following immunization.
      The impact of the immunization on the dynamics of tumor angiogenesis was assessed
      by temporal noninvasive dynamic contrast-enhanced magnetic resonance imaging and
      was further confirmed by histologic study and vascular count. Through the
      experiments of in vivo depletion and adoptive transfer, CD4 T cells were
      identified as effectors that depend on IFN-gamma for tumor prevention. The
      response was further verified by the identification of an MHC H-2 I-E(d)
      restricted peptide derived from N-LMP1 and by the immunization of mice with N
      LMP1 peptide-loaded dendritic cells. These studies provide insight into N-LMP1
      specific immunity in vivo, which suggests that CD4 T cells may play an important
      role in angiogenic surveillance against LMP1-associated cancer via tumor stroma
      targeting. 

PMID- 25847975
TI  - CCL7 and IRF-7 Mediate Hallmark Inflammatory and IFN Responses following
      Rhinovirus 1B Infection.
AB  - Rhinovirus (RV) infections are common and have the potential to exacerbate
      asthma. We have determined the lung transcriptome in RV strain 1B-infected naive
      BALB/c mice (nonallergic) and identified CCL7 and IFN regulatory factor (IRF)-7
      among the most upregulated mRNA transcripts in the lung. To investigate their
      roles we employed anti-CCL7 Abs and an IRF-7-targeting small interfering RNA in
      vivo. Neutralizing CCL7 or inhibiting IRF-7 limited neutrophil and macrophage
      influx and IFN responses in nonallergic mice. Neutralizing CCL7 also reduced
      activation of NF-kappaB p65 and p50 subunits, as well as airway hyperreactivity
      (AHR) in nonallergic mice. However, neither NF-kappaB subunit activation nor AHR
      was abolished with infection of allergic mice after neutralizing CCL7, despite a
      reduction in the number of neutrophils, macrophages, and eosinophils. IRF-7 small
      interfering RNA primarily suppressed IFN-alpha and IFN-beta levels during
      infection of allergic mice. Our data highlight a pivotal role of CCL7 and IRF-7
      in RV-induced inflammation and IFN responses and link NF-kappaB signaling to the
      development of AHR. 

PMID- 25847976
TI  - The world alliance against antibiotic resistance: consensus for a declaration.
AB  - Antibiotic resistance is increasing worldwide and has become a very important
      threat to public health. The overconsumption of antibiotics is the most important
      cause of this problem. We created a World Alliance Against Antibiotic Resistance
      (WAAAR), which now includes 720 people from 55 different countries and is
      supported by 145 medical societies or various groups. In June 2014, WAAAR
      launched a declaration against antibiotic resistance. This article describes the
      process and the content of this declaration. 

PMID- 25847977
TI  - Clinical outcomes associated with respiratory virus detection before allogeneic
      hematopoietic stem cell transplant.
AB  - BACKGROUND: The management of respiratory virus infections prior to hematopoietic
      cell transplant (HCT) is difficult. We examined whether respiratory virus
      detection before HCT influenced the requirement for bronchoscopy,
      hospitalization, and overall survival following HCT. METHODS: Pre-HCT and weekly
      post-HCT nasal washes were collected through day 100 from patients with and
      without symptoms. Samples were tested by multiplex polymerase chain reaction for
      respiratory syncytial virus, parainfluenza viruses 1-4, influenza A and B, human
      metapneumovirus, adenovirus, and human rhinoviruses, coronaviruses, and
      bocavirus. RESULTS: Of 458 patients, 116 (25%) had respiratory viruses detected
      pre-HCT. Overall, patients with viruses detected pre-HCT had fewer days alive and
      out of the hospital and lower survival at day 100 (adjusted hazard ratio [aHR],
      2.4; 95% confidence interval [CI], 1.3-4.5; P = .007) than patients with negative
      samples; this risk was also present with rhinovirus alone (aHR for mortality,
      2.6; 95% CI, 1.2-5.5; P = .01). No difference in bronchoscopy incidence was seen
      in patients with and without respiratory viruses (aHR, 1.3; 95% CI, .8-2.0; P =
      .32). In symptomatic patients, those with respiratory viruses detected had
      increased overall mortality compared with patients without viruses detected
      (unadjusted HR, 3.5; 95% CI, 1.0-12.1; P = .05); among asymptomatic patients,
      detection of respiratory viruses was not associated with increased mortality.
      CONCLUSIONS: These data support routine testing for respiratory viruses among
      symptomatic patients before HCT, and delay of transplant with virus detection
      when feasible, even for detection of rhinovirus alone. Further study is needed to
      address whether asymptomatic patients should undergo screening for respiratory
      virus detection before HCT.

PMID- 25847978
TI  - Back to the future: improving the use of guidelines-recommended coronary disease
      secondary prevention at the dawn of the precision medicine era.

PMID- 25847980
TI  - Percutaneous interventions in aortic disease.

PMID- 25847979
TI  - Optimal medical therapy improves clinical outcomes in patients undergoing
      revascularization with percutaneous coronary intervention or coronary artery
      bypass grafting: insights from the Synergy Between Percutaneous Coronary
      Intervention with TAXUS and Cardiac Surgery (SYNTAX) trial at the 5-year follow
      up.
AB  - BACKGROUND: There is a paucity of data on the use of optimal medical therapy
      (OMT) in patients with complex coronary artery disease undergoing
      revascularization with percutaneous coronary intervention or coronary artery
      bypass grafting (CABG) and its long-term prognostic significance. METHODS AND
      RESULTS: The Synergy Between Percutaneous Coronary Intervention With TAXUS and
      Cardiac Surgery (SYNTAX) trial is a multicenter, randomized, clinical trial of
      patients (n=1800) with complex coronary disease randomized to revascularization
      with percutaneous coronary intervention or CABG. Detailed drug history was
      collected for all patients at discharge and at the 1-month, 6-month, 1-year, 3
      year, and 5-year follow-ups. OMT was defined as the combination of at least 1
      antiplatelet drug, statin, beta-blocker, and angiotensin-converting enzyme
      inhibitor/angiotensin receptor blocker. Five-year clinical outcomes were
      stratified by OMT and non-OMT. OMT was underused in patients treated with
      coronary revascularization, especially CABG. OMT was an independent predictor of
      survival. OMT was associated with a significant reduction in mortality (hazard
      ratio, 0.64; 95% confidence interval, 0.48-0.85; P=0.002) and composite end point
      of death/myocardial infarction/stroke (hazard ratio, 0.73; 95% confidence
      interval, 0.58-0.92; P=0.007) at the 5-year follow-up. The treatment effect with
      OMT (36% relative reduction in mortality over 5 years) was greater than the
      treatment effect of revascularization strategy (26% relative reduction in
      mortality with CABG versus percutaneous coronary intervention over 5 years). On
      stratified analysis, all the components of OMT were important for reducing
      adverse outcomes regardless of revascularization strategy. CONCLUSIONS: The use
      of OMT remains low in patients with complex coronary disease requiring coronary
      intervention with percutaneous coronary intervention and even lower in patients
      treated with CABG. Lack of OMT is associated with adverse clinical outcomes.
      Targeted strategies to improve OMT use in postrevascularization patients are
      warranted. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov.
      Unique identifier: NCT00114972.

PMID- 25847981
TI  - ECG response: April 7, 2015.

PMID- 25847983
TI  - "Prancing" heart with pericardial injury.

PMID- 25847982
TI  - Coronary artery rupture caused by stent infection: a rare complication.

PMID- 25847984
TI  - Letter by Usui et al regarding article, "Inhibition of interleukin-1beta
      decreases aneurysm formation and progression in a novel model of thoracic aortic
      aneurysm".

PMID- 25847985
TI  - Response to letter regarding article, "Inhibition of interleukin-1beta decreases
      aneurysm formation and progression in a novel model of thoracic aortic aneurysm".

PMID- 25847986
TI  - Correction. 9-Cis retinoic acid promotes lymphangiogenesis and enhances lymphatic
      vessel regeneration: therapeutic implications of 9-Cis retinoic acid for
      secondary lymphedema.

PMID- 25847987
TI  - Correction. Cumulative effect of psychosocial factors in youth on ideal
      cardiovascular health in adulthood: the Cardiovascular Risk in Young Finns Study.

PMID- 25847989
TI  - Next-Generation Sequencing: Targeting Targeted Therapies.
AB  - Next-generation sequencing (NGS) has given new perspective in oncology. With the
      ongoing development of targeted therapies, NGS is evolving molecular diagnostics
      by providing comprehensive interrogation of clinically actionable genomic
      aberrations in tumors. Having this assay as the primary testing method produces
      clinically beneficial results. See related article by Drilon et al., p. 3631.

PMID- 25847988
TI  - Sudden cardiac arrest during sports activity in middle age.
AB  - BACKGROUND: Sports-associated sudden cardiac arrests (SCAs) occur mostly during
      middle age. We sought to determine the burden, characteristics, and outcomes of
      SCA during sports among middle-aged residents of a large US community. METHODS
      AND RESULTS: Patients with SCA who were 35 to 65 years of age were identified in
      a large, prospective, population-based study (2002-2013), with systematic and
      comprehensive assessment of their lifetime medical history. Of the 1247 SCA
      cases, 63 (5%) occurred during sports activities at a mean age of 51.1+/-8.8
      years, yielding an incidence of 21.7 (95% confidence interval, 8.1-35.4) per 1
      million per year. The incidence varied significantly by sex, with a higher
      incidence among men (relative risk, 18.68; 95% confidence interval, 2.50-139.56)
      for sports SCAs compared with all other SCAs (relative risk 2.58; 95% confidence
      interval, 2.12-3.13). Sports SCA was also more likely to be a witnessed event
      (87% versus 53%; P<0.001) with cardiopulmonary resuscitation (44% versus 25%;
      P=0.001) and ventricular fibrillation (84% versus 51%; P<0.0001). Survival to
      hospital discharge was higher for sports-associated SCA (23.2% versus 13.6%;
      P=0.04). Sports SCA cases presented with known preexisting cardiac disease in 16%
      and >=1 cardiovascular risk factors in 56%, and overall, 36% of cases had typical
      cardiovascular symptoms during the week preceding the SCA. CONCLUSIONS: Sports
      associated SCA in middle age represents a relatively small proportion of the
      overall SCA burden, reinforcing the idea of the high-benefit, low-risk nature of
      sports activity. Especially in light of current population aging trends, our
      findings emphasize that targeted education could maximize both safety and
      acceptance of sports activity in the older athlete.

PMID- 25847990
TI  - Noninvasive prenatal diagnosis of duchenne muscular dystrophy: comprehensive
      genetic diagnosis in carrier, proband, and fetus.
AB  - BACKGROUND: Noninvasive prenatal diagnosis of monogenic disorders using maternal
      plasma and targeted massively parallel sequencing is being investigated actively.
      We previously demonstrated that comprehensive genetic diagnosis of a Duchenne
      muscular dystrophy (DMD) patient is feasible using a single targeted sequencing
      platform. Here we demonstrate the applicability of this approach to carrier
      detection and noninvasive prenatal diagnosis. METHODS: Custom solution-based
      target enrichment was designed to cover the entire dystrophin (DMD) gene region.
      Targeted massively parallel sequencing was performed using genomic DNA from 4
      mother and proband pairs to test whether carrier status could be detected
      reliably. Maternal plasma DNA at varying gestational weeks was collected from the
      same families and sequenced using the same targeted platform to predict the
      inheritance of the DMD mutation by their fetus. Overrepresentation of an
      inherited allele was determined by comparing the allele fraction of 2 phased
      haplotypes after examining and correcting for the recombination event. RESULTS:
      The carrier status of deletion/duplication and point mutations was detected
      reliably through using a single targeted massively parallel sequencing platform.
      Whether the fetus had inherited the DMD mutation was predicted correctly in all 4
      families as early as 6 weeks and 5 days of gestation. In one of these, detection
      of the recombination event and reconstruction of the phased haplotype produced a
      correct diagnosis. CONCLUSIONS: Noninvasive prenatal diagnosis of DMD is feasible
      using a single targeted massively parallel sequencing platform with tiling
      design.

PMID- 25847992
TI  - Cities, traffic, and CO2: A multidecadal assessment of trends, drivers, and
      scaling relationships.
AB  - Emissions of CO2 from road vehicles were 1.57 billion metric tons in 2012,
      accounting for 28% of US fossil fuel CO2 emissions, but the spatial distributions
      of these emissions are highly uncertain. We develop a new emissions inventory,
      the Database of Road Transportation Emissions (DARTE), which estimates CO2
      emitted by US road transport at a resolution of 1 km annually for 1980-2012.
      DARTE reveals that urban areas are responsible for 80% of on-road emissions
      growth since 1980 and for 63% of total 2012 emissions. We observe nonlinearities
      between CO2 emissions and population density at broad spatial/temporal scales,
      with total on-road CO2 increasing nonlinearly with population density, rapidly up
      to 1,650 persons per square kilometer and slowly thereafter. Per capita emissions
      decline as density rises, but at markedly varying rates depending on existing
      densities. We make use of DARTE's bottom-up construction to highlight the biases
      associated with the common practice of using population as a linear proxy for
      disaggregating national- or state-scale emissions. Comparing DARTE with existing
      downscaled inventories, we find biases of 100% or more in the spatial
      distribution of urban and rural emissions, largely driven by mismatches between
      inventory downscaling proxies and the actual spatial patterns of vehicle activity
      at urban scales. Given cities' dual importance as sources of CO2 and an emerging
      nexus of climate mitigation initiatives, high-resolution estimates such as DARTE
      are critical both for accurately quantifying surface carbon fluxes and for
      verifying the effectiveness of emissions mitigation efforts at urban scales. 

PMID- 25847991
TI  - Glucocorticoid receptor regulates accurate chromosome segregation and is
      associated with malignancy.
AB  - The glucocorticoid receptor (GR) is a member of the nuclear receptor superfamily,
      which controls programs regulating cell proliferation, differentiation, and
      apoptosis. We have identified an unexpected role for GR in mitosis. We discovered
      that specifically modified GR species accumulate at the mitotic spindle during
      mitosis in a distribution that overlaps with Aurora kinases. We found that Aurora
      A was required to mediate mitosis-driven GR phosphorylation, but not recruitment
      of GR to the spindle. GR was necessary for mitotic progression, with increased
      time to complete mitosis, frequency of mitotic aberrations, and death in mitosis
      observed following GR knockdown. Complementation studies revealed an essential
      role for the GR ligand-binding domain, but no clear requirement for ligand
      binding in regulating chromosome segregation. The GR N-terminal domain, and
      specifically phosphosites S203 and S211, were not required. Reduced GR expression
      results in a cell cycle phenotype, with isolated cells from mouse and human
      subjects showing changes in chromosome content over prolonged passage.
      Furthermore, GR haploinsufficient mice have an increased incidence of tumor
      formation, and, strikingly, these tumors are further depleted for GR, implying
      additional GR loss as a consequence of cell transformation. We identified reduced
      GR expression in a panel of human liver, lung, prostate, colon, and breast
      cancers. We therefore reveal an unexpected role for the GR in promoting accurate
      chromosome segregation during mitosis, which is causally linked to tumorigenesis,
      making GR an authentic tumor suppressor gene. 

PMID- 25847993
TI  - Rgg protein structure-function and inhibition by cyclic peptide compounds.
AB  - Peptide pheromone cell-cell signaling (quorum sensing) regulates the expression
      of diverse developmental phenotypes (including virulence) in Firmicutes, which
      includes common human pathogens, e.g., Streptococcus pyogenes and Streptococcus
      pneumoniae. Cytoplasmic transcription factors known as "Rgg proteins" are peptide
      pheromone receptors ubiquitous in Firmicutes. Here we present X-ray crystal
      structures of a Streptococcus Rgg protein alone and in complex with a tight
      binding signaling antagonist, the cyclic undecapeptide cyclosporin A. To our
      knowledge, these represent the first Rgg protein X-ray crystal structures. Based
      on the results of extensive structure-function analysis, we reveal the peptide
      pheromone-binding site and the mechanism by which cyclosporin A inhibits
      activation of the peptide pheromone receptor. Guided by the Rgg-cyclosporin A
      complex structure, we predicted that the nonimmunosuppressive cyclosporin A
      analog valspodar would inhibit Rgg activation. Indeed, we found that, like
      cyclosporin A, valspodar inhibits peptide pheromone activation of conserved Rgg
      proteins in medically relevant Streptococcus species. Finally, the crystal
      structures presented here revealed that the Rgg protein DNA-binding domains are
      covalently linked across their dimerization interface by a disulfide bond formed
      by a highly conserved cysteine. The DNA-binding domain dimerization interface
      observed in our structures is essentially identical to the interfaces previously
      described for other members of the XRE DNA-binding domain family, but the
      presence of an intermolecular disulfide bond buried in this interface appears to
      be unique. We hypothesize that this disulfide bond may, under the right
      conditions, affect Rgg monomer-dimer equilibrium, stabilize Rgg conformation, or
      serve as a redox-sensitive switch. 

PMID- 25847994
TI  - Long-acting progestin-only contraceptives impair endometrial vasculature by
      inhibiting uterine vascular smooth muscle cell survival.
AB  - Molecular mechanisms responsible for abnormal endometrial vasculature in women
      receiving long-acting progestin-only contraceptives (LAPCs) are unknown. We
      hypothesize that LAPCs impair vascular smooth muscle cell (VSMC) and pericyte
      proliferation and migration producing thin-walled hyperdilated fragile
      microvessels prone to bleeding. Proliferating cell nuclear antigen (PCNA) and
      alpha-smooth muscle actin (alphaSMA) double-immunostaining assessed VSMC
      differentiation and proliferation in endometria from women before and after
      DepoProvera (Depo) treatment and from oophorectomized guinea pigs (OVX-GPs)
      treated with vehicle, estradiol (E2), medroxyprogesterone acetate (MPA), or
      E2+MPA. Whole-genome profiling, proliferation, and migration assays were
      performed on cultured VSMCs treated with MPA or etonogestrel (ETO). Endometrial
      vessels of Depo-administered women displayed reduced alphaSMA immunoreactivity
      and fewer PCNA (+) nuclei among alphaSMA (+) cells (P < 0.008). Microarray
      analysis of VSMCs identified several MPA- and ETO-altered transcripts regulated
      by STAT1 signaling (P < 2.22 * 10(-6)), including chemokine (C-C motif) ligand 2
      (CCL2). Both MPA and ETO reduce VSMC proliferation and migration (P < 0.001).
      Recombinant CCL2 reversed this progestin-mediated inhibition, whereas a STAT1
      inhibitor abolished the CCL2 effect. Similarly, the endometria of MPA treated OVX
      GPs displayed decreased alphaSMA staining and fewer PCNA (+) nuclei in VSMC (P <
      0.005). In conclusion, LAPCs promote abnormal endometrial vessel formation by
      inhibiting VSMC proliferation and migration. 

PMID- 25847995
TI  - US protected lands mismatch biodiversity priorities.
AB  - Because habitat loss is the main cause of extinction, where and how much society
      chooses to protect is vital for saving species. The United States is well
      positioned economically and politically to pursue habitat conservation should it
      be a societal goal. We assessed the US protected area portfolio with respect to
      biodiversity in the country. New synthesis maps for terrestrial vertebrates,
      freshwater fish, and trees permit comparison with protected areas to identify
      priorities for future conservation investment. Although the total area protected
      is substantial, its geographic configuration is nearly the opposite of patterns
      of endemism within the country. Most protected lands are in the West, whereas the
      vulnerable species are largely in the Southeast. Private land protections are
      significant, but they are not concentrated where the priorities are. To
      adequately protect the nation's unique biodiversity, we recommend specific areas
      deserving additional protection, some of them including public lands, but many
      others requiring private investment. 

PMID- 25847996
TI  - Stress sigma factor RpoS degradation and translation are sensitive to the state
      of central metabolism.
AB  - RpoS, the stationary phase/stress sigma factor of Escherichia coli, regulates a
      large cohort of genes important for the cell to deal with suboptimal conditions.
      Its level increases quickly in the cell in response to many stresses and returns
      to low levels when growth resumes. Increased RpoS results from increased
      translation and decreased RpoS degradation. Translation is positively regulated
      by small RNAs (sRNAs). Protein stability is positively regulated by anti
      adaptors, which prevent the RssB adaptor-mediated degradation of RpoS by the
      ClpXP protease. Inactivation of aceE, a subunit of pyruvate dehydrogenase (PDH),
      was found to increase levels of RpoS by affecting both translation and protein
      degradation. The stabilization of RpoS in aceE mutants is dependent on increased
      transcription and translation of IraP and IraD, two known anti-adaptors. The aceE
      mutation also leads to a significant increase in rpoS translation. The sRNAs
      known to positively regulate RpoS are not responsible for the increased
      translation; sequences around the start codon are sufficient for the induction of
      translation. PDH synthesizes acetyl-CoA; acetate supplementation allows the cell
      to synthesize acetyl-CoA by an alternative, less favored pathway, in part
      dependent upon RpoS. Acetate addition suppressed the effects of the aceE mutant
      on induction of the anti-adaptors, RpoS stabilization, and rpoS translation.
      Thus, the bacterial cell responds to lowered levels of acetyl-CoA by inducing
      RpoS, allowing reprogramming of E. coli metabolism. 

PMID- 25847998
TI  - Homologous ligands accommodated by discrete conformations of a buried cavity.
AB  - Conformational change in protein-ligand complexes is widely modeled, but the
      protein accommodation expected on binding a congeneric series of ligands has
      received less attention. Given their use in medicinal chemistry, there are
      surprisingly few substantial series of congeneric ligand complexes in the Protein
      Data Bank (PDB). Here we determine the structures of eight alkyl benzenes, in
      single-methylene increases from benzene to n-hexylbenzene, bound to an enclosed
      cavity in T4 lysozyme. The volume of the apo cavity suffices to accommodate
      benzene but, even with toluene, larger cavity conformations become observable in
      the electron density, and over the series two other major conformations are
      observed. These involve discrete changes in main-chain conformation, expanding
      the site; few continuous changes in the site are observed. In most structures,
      two discrete protein conformations are observed simultaneously, and energetic
      considerations suggest that these conformations are low in energy relative to the
      ground state. An analysis of 121 lysozyme cavity structures in the PDB finds that
      these three conformations dominate the previously determined structures, largely
      modeled in a single conformation. An investigation of the few congeneric series
      in the PDB suggests that discrete changes are common adaptations to a series of
      growing ligands. The discrete, but relatively few, conformational states observed
      here, and their energetic accessibility, may have implications for anticipating
      protein conformational change in ligand design. 

PMID- 25847997
TI  - Cortical activity is more stable when sensory stimuli are consciously perceived.
AB  - According to recent evidence, stimulus-tuned neurons in the cerebral cortex
      exhibit reduced variability in firing rate across trials, after the onset of a
      stimulus. However, in order for a reduction in variability to be directly
      relevant to perception and behavior, it must be realized within trial--the
      pattern of activity must be relatively stable. Stability is characteristic of
      decision states in recurrent attractor networks, and its possible relevance to
      conscious perception has been suggested by theorists. However, it is difficult to
      measure on the within-trial time scales and broadly distributed spatial scales
      relevant to perception. We recorded simultaneous magneto- and
      electroencephalography (MEG and EEG) data while subjects observed threshold-level
      visual stimuli. Pattern-similarity analyses applied to the data from MEG
      gradiometers uncovered a pronounced decrease in variability across trials after
      stimulus onset, consistent with previous single-unit data. This was followed by a
      significant divergence in variability depending upon subjective report
      (seen/unseen), with seen trials exhibiting less variability. Applying the same
      analysis across time, within trial, we found that the latter effect coincided in
      time with a difference in the stability of the pattern of activity. Stability
      alone could be used to classify data from individual trials as "seen" or
      "unseen." The same metric applied to EEG data from patients with disorders of
      consciousness exposed to auditory stimuli diverged parametrically according to
      clinically diagnosed level of consciousness. Differences in signal strength could
      not account for these results. Conscious perception may involve the transient
      stabilization of distributed cortical networks, corresponding to a global brain
      scale decision.

PMID- 25847999
TI  - Edaravone alleviates Alzheimer's disease-type pathologies and cognitive deficits.
AB  - Alzheimer's disease (AD) is one of most devastating diseases affecting elderly
      people. Amyloid-beta (Abeta) accumulation and the downstream pathological events
      such as oxidative stress play critical roles in pathogenesis of AD. Lessons from
      failures of current clinical trials suggest that targeting multiple key pathways
      of the AD pathogenesis is necessary to halt the disease progression. Here we show
      that Edaravone, a free radical scavenger that is marketed for acute ischemic
      stroke, has a potent capacity of inhibiting Abeta aggregation and attenuating
      Abeta-induced oxidation in vitro. When given before or after the onset of Abeta
      deposition via i.p. injection, Edaravone substantially reduces Abeta deposition,
      alleviates oxidative stress, attenuates the downstream pathologies including Tau
      hyperphosphorylation, glial activation, neuroinflammation, neuronal loss,
      synaptic dysfunction, and rescues the behavioral deficits of APPswe/PS1 mice.
      Oral administration of Edaravone also ameliorates the AD-like pathologies and
      memory deficits of the mice. These findings suggest that Edaravone holds a
      promise as a therapeutic agent for AD by targeting multiple key pathways of the
      disease pathogenesis. 

PMID- 25848001
TI  - Time-dependent sequestration of RVE8 by LNK proteins shapes the diurnal
      oscillation of anthocyanin biosynthesis.
AB  - Circadian clocks sustain 24-h rhythms in physiology and metabolism that are
      synchronized with the day/night cycle. In plants, the regulatory network
      responsible for the generation of rhythms has been broadly investigated over the
      past years. However, little is known about the intersecting pathways that link
      the environmental signals with rhythms in cellular metabolism. Here, we examine
      the role of the circadian components REVEILLE8/LHY-CCA1-LIKE5 (RVE8/LCL5) and
      NIGHT LIGHT-INDUCIBLE AND CLOCK-REGULATED genes (LNK) shaping the diurnal
      oscillation of the anthocyanin metabolic pathway. Around dawn, RVE8 up-regulates
      anthocyanin gene expression by directly associating to the promoters of a subset
      of anthocyanin biosynthetic genes. The up-regulation is overcome at midday by the
      repressing activity of LNK proteins, as inferred by the increased anthocyanin
      gene expression in lnk1/lnk2 double mutant plants. Chromatin immunoprecipitation
      assays using LNK and RVE8 misexpressing plants show that RVE8 binding to target
      promoters is precluded in LNK overexpressing plants and conversely, binding is
      enhanced in the absence of functional LNKs, which provides a mechanism by which
      LNKs antagonize RVE8 function in the regulation of anthocyanin accumulation.
      Based on their previously described transcriptional coactivating function, our
      study defines a switch in the regulatory activity of RVE8-LNK interaction, from a
      synergic coactivating role of evening-expressed clock genes to a repressive
      antagonistic function modulating anthocyanin biosynthesis around midday. 

PMID- 25848000
TI  - Maternal and zygotic Zfp57 modulate NOTCH signaling in cardiac development.
AB  - Zfp57 is a maternal-zygotic effect gene that maintains genomic imprinting. Here
      we report that Zfp57 mutants exhibited a variety of cardiac defects including
      atrial septal defect (ASD), ventricular septal defect (VSD), thin myocardium, and
      reduced trabeculation. Zfp57 maternal-zygotic mutant embryos displayed more
      severe phenotypes with higher penetrance than the zygotic ones. Cardiac
      progenitor cells exhibited proliferation and differentiation defects in Zfp57
      mutants. ZFP57 is a master regulator of genomic imprinting, so the DNA
      methylation imprint was lost in embryonic heart without ZFP57. Interestingly, the
      presence of imprinted DLK1, a target of ZFP57, correlated with NOTCH1 activation
      in cardiac cells. These results suggest that ZFP57 may modulate NOTCH signaling
      during cardiac development. Indeed, loss of ZFP57 caused loss of NOTCH1
      activation in embryonic heart with more severe loss observed in the maternal
      zygotic mutant. Maternal and zygotic functions of Zfp57 appear to play redundant
      roles in NOTCH1 activation and cardiomyocyte differentiation. This serves as an
      example of a maternal effect that can influence mammalian organ development. It
      also links genomic imprinting to NOTCH signaling and particular developmental
      functions. 

PMID- 25848002
TI  - Structural basis for substrate specificity of an amino acid ABC transporter.
AB  - ATP-binding cassette (ABC) transporters are ubiquitous integral membrane proteins
      that translocate a variety of substrates, ranging from ions to macromolecules,
      either out of or into the cytosol (hence defined as importers or exporters,
      respectively). It has been demonstrated that ABC exporters and importers function
      through a common mechanism involving conformational switches between inward
      facing and outward-facing states; however, the mechanism underlying their
      functions, particularly substrate recognition, remains elusive. Here we report
      the structures of an amino acid ABC importer Art(QN)2 from Thermoanaerobacter
      tengcongensis composed of homodimers each of the transmembrane domain ArtQ and
      the nucleotide-binding domain ArtN, either in its apo form or in complex with
      substrates (Arg, His) and/or ATPs. The structures reveal that the straddling of
      the TMDs around the twofold axis forms a substrate translocation pathway across
      the membrane. Interestingly, each TMD has a negatively charged pocket that
      together create a negatively charged internal tunnel allowing amino acids
      carrying positively charged groups to pass through. Our structural and functional
      studies provide a better understanding of how ABC transporters select and
      translocate their substrates. 

PMID- 25848003
TI  - New functional insights into the internal architecture of the laminated anchor
      spicules of Euplectella aspergillum.
AB  - To adapt to a wide range of physically demanding environmental conditions,
      biological systems have evolved a diverse variety of robust skeletal
      architectures. One such example, Euplectella aspergillum, is a sediment-dwelling
      marine sponge that is anchored into the sea floor by a flexible holdfast
      apparatus consisting of thousands of anchor spicules (long, hair-like glassy
      fibers). Each spicule is covered with recurved barbs and has an internal
      architecture consisting of a solid core of silica surrounded by an assembly of
      coaxial silica cylinders, each of which is separated by a thin organic layer. The
      thickness of each silica cylinder progressively decreases from the spicule's core
      to its periphery, which we hypothesize is an adaptation for redistributing
      internal stresses, thus increasing the overall strength of each spicule. To
      evaluate this hypothesis, we created a spicule structural mechanics model, in
      which we fixed the radii of the silica cylinders such that the force transmitted
      from the surface barbs to the remainder of the skeletal system was maximized.
      Compared with measurements of these parameters in the native sponge spicules, our
      modeling results correlate remarkably well, highlighting the beneficial nature of
      this elastically heterogeneous lamellar design strategy. The structural
      principles obtained from this study thus provide potential design insights for
      the fabrication of high-strength beams for load-bearing applications through the
      modification of their internal architecture, rather than their external geometry.

PMID- 25848004
TI  - Octopamine mediates starvation-induced hyperactivity in adult Drosophila.
AB  - Starved animals often exhibit elevated locomotion, which has been speculated to
      partly resemble foraging behavior and facilitate food acquisition and energy
      intake. Despite its importance, the neural mechanism underlying this behavior
      remains unknown in any species. In this study we confirmed and extended previous
      findings that starvation induced locomotor activity in adult fruit flies
      Drosophila melanogaster. We also showed that starvation-induced hyperactivity was
      directed toward the localization and acquisition of food sources, because it
      could be suppressed upon the detection of food cues via both central nutrient
      sensing and peripheral sweet-sensing mechanisms, via induction of food ingestion.
      We further found that octopamine, the insect counterpart of vertebrate
      norepinephrine, as well as the neurons expressing octopamine, were both necessary
      and sufficient for starvation-induced hyperactivity. Octopamine was not required
      for starvation-induced changes in feeding behaviors, suggesting independent
      regulations of energy intake behaviors upon starvation. Taken together, our
      results establish a quantitative behavioral paradigm to investigate the
      regulation of energy homeostasis by the CNS and identify a conserved neural
      substrate that links organismal metabolic state to a specific behavioral output. 

PMID- 25848005
TI  - Cadmium-cysteine coordination in the BK inner pore region and its structural and
      functional implications.
AB  - To probe structure and gating-associated conformational changes in BK-type
      potassium (BK) channels, we examined consequences of Cd(2+) coordination with
      cysteines introduced at two positions in the BK inner pore. At V319C, the
      equivalent of valine in the conserved Kv proline-valine-proline (PVP) motif,
      Cd(2+) forms intrasubunit coordination with a native glutamate E321, which would
      place the side chains of V319C and E321 much closer together than observed in
      voltage-dependent K(+) (Kv) channel structures, requiring that the proline
      between V319C and E321 introduces a kink in the BK S6 inner helix sharper than
      that observed in Kv channel structures. At inner pore position A316C, Cd(2+)
      binds with modest state dependence, suggesting the absence of an ion permeation
      gate at the cytosolic side of BK channel. These results highlight fundamental
      structural differences between BK and Kv channels in their inner pore region,
      which likely underlie differences in voltage-dependent gating between these
      channels. 

PMID- 25848006
TI  - Salmonella promotes virulence by repressing cellulose production.
AB  - Cellulose is the most abundant organic polymer on Earth. In bacteria, cellulose
      confers protection against environmental insults and is a constituent of biofilms
      typically formed on abiotic surfaces. We report that, surprisingly, Salmonella
      enterica serovar Typhimurium makes cellulose when inside macrophages. We
      determine that preventing cellulose synthesis increases virulence, whereas
      stimulation of cellulose synthesis inside macrophages decreases virulence. An
      attenuated mutant lacking the mgtC gene exhibited increased cellulose levels due
      to increased expression of the cellulose synthase gene bcsA and of cyclic
      diguanylate, the allosteric activator of the BcsA protein. Inactivation of bcsA
      restored wild-type virulence to the Salmonella mgtC mutant, but not to other
      attenuated mutants displaying a wild-type phenotype regarding cellulose. Our
      findings indicate that a virulence determinant can promote pathogenicity by
      repressing a pathogen's antivirulence trait. Moreover, they suggest that
      controlling antivirulence traits increases long-term pathogen fitness by
      mediating a trade-off between acute virulence and transmission. 

PMID- 25848007
TI  - Asphyxia-activated corticocardiac signaling accelerates onset of cardiac arrest.
AB  - The mechanism by which the healthy heart and brain die rapidly in the absence of
      oxygen is not well understood. We performed continuous electrocardiography and
      electroencephalography in rats undergoing experimental asphyxia and analyzed
      cortical release of core neurotransmitters, changes in brain and heart electrical
      activity, and brain-heart connectivity. Asphyxia stimulates a robust and
      sustained increase of functional and effective cortical connectivity, an
      immediate increase in cortical release of a large set of neurotransmitters, and a
      delayed activation of corticocardiac functional and effective connectivity that
      persists until the onset of ventricular fibrillation. Blocking the brain's
      autonomic outflow significantly delayed terminal ventricular fibrillation and
      lengthened the duration of detectable cortical activities despite the continued
      absence of oxygen. These results demonstrate that asphyxia activates a
      brainstorm, which accelerates premature death of the heart and the brain. 

PMID- 25848008
TI  - Estrogen receptor beta exon 3-deleted mouse: The importance of non-ERE pathways
      in ERbeta signaling.
AB  - In 1998, an estrogen receptor beta (ERbeta) knockout (KO) mouse was created by
      interrupting the gene at the DNA binding domain (DBD) with a neocassette. The
      mutant females were subfertile and there were abnormalities in the brain,
      prostate, lung, colon, and immune system. In 2008, another ERbeta mutant mouse
      was generated by deleting ERbeta exon 3 which encodes the first zinc finger in
      the DBD. The female mice of this strain were unable to ovulate but were otherwise
      normal. The differences in the phenotypes of the two KO strains, have led to
      questions about the physiological function of ERbeta. In the present study, we
      created an ERbeta exon 3-deleted mouse (ERbeta-Deltaex3) and confirmed that the
      only observable defect was anovulation. Despite the two in-frame stop codons
      introduced by splicing between exons 2 and 4, an ERbeta protein was expressed in
      nuclei of prostate epithelial cells. Using two different anti-ERbeta antibodies,
      we showed that an in-frame ligand binding domain and C terminus were present in
      the ERbeta-Deltaex3 protein. Moreover, with nuclear extracts from ERbeta-Deltaex3
      prostates, there was an ERbeta-dependent retardation of migration of activator
      protein-1 response elements in EMSA. Unlike the original knockout mouse,
      expression of Ki67, androgen receptor, and Dachshund-1 in prostate epithelium was
      not altered in the ERbeta-Deltaex3 mouse. We conclude that very little of ERbeta
      transcriptional activity depends on binding to classical estrogen response
      elements (EREs). 

PMID- 25848009
TI  - Cadherin-related family member 3, a childhood asthma susceptibility gene product,
      mediates rhinovirus C binding and replication.
AB  - Members of rhinovirus C (RV-C) species are more likely to cause wheezing
      illnesses and asthma exacerbations compared with other rhinoviruses. The cellular
      receptor for these viruses was heretofore unknown. We report here that expression
      of human cadherin-related family member 3 (CDHR3) enables the cells normally
      unsusceptible to RV-C infection to support both virus binding and replication. A
      coding single nucleotide polymorphism (rs6967330, C529Y) was previously linked to
      greater cell-surface expression of CDHR3 protein, and an increased risk of
      wheezing illnesses and hospitalizations for childhood asthma. Compared with wild
      type CDHR3, cells transfected with the CDHR3-Y529 variant had about 10-fold
      increases in RV-C binding and progeny yields. We developed a transduced HeLa cell
      line (HeLa-E8) stably expressing CDHR3-Y529 that supports RV-C propagation in
      vitro. Modeling of CDHR3 structure identified potential binding sites that could
      impact the virus surface in regions that are highly conserved among all RV-C
      types. Our findings identify that the asthma susceptibility gene product CDHR3
      mediates RV-C entry into host cells, and suggest that rs6967330 mutation could be
      a risk factor for RV-C wheezing illnesses. 

PMID- 25848010
TI  - Insights into the origins of fish hunting in venomous cone snails from studies of
      Conus tessulatus.
AB  - Prey shifts in carnivorous predators are events that can initiate the accelerated
      generation of new biodiversity. However, it is seldom possible to reconstruct how
      the change in prey preference occurred. Here we describe an evolutionary "smoking
      gun" that illuminates the transition from worm hunting to fish hunting among
      marine cone snails, resulting in the adaptive radiation of fish-hunting lineages
      comprising ~100 piscivorous Conus species. This smoking gun is delta-conotoxin
      TsVIA, a peptide from the venom of Conus tessulatus that delays inactivation of
      vertebrate voltage-gated sodium channels. C. tessulatus is a species in a worm
      hunting clade, which is phylogenetically closely related to the fish-hunting cone
      snail specialists. The discovery of a delta-conotoxin that potently acts on
      vertebrate sodium channels in the venom of a worm-hunting cone snail suggests
      that a closely related ancestral toxin enabled the transition from worm hunting
      to fish hunting, as delta-conotoxins are highly conserved among fish hunters and
      critical to their mechanism of prey capture; this peptide, delta-conotoxin TsVIA,
      has striking sequence similarity to these delta-conotoxins from piscivorous cone
      snail venoms. Calcium-imaging studies on dissociated dorsal root ganglion (DRG)
      neurons revealed the peptide's putative molecular target (voltage-gated sodium
      channels) and mechanism of action (inhibition of channel inactivation). The
      results were confirmed by electrophysiology. This work demonstrates how
      elucidating the specific interactions between toxins and receptors from
      phylogenetically well-defined lineages can uncover molecular mechanisms that
      underlie significant evolutionary transitions. 

PMID- 25848011
TI  - Mitigation of acute kidney injury by cell-cycle inhibitors that suppress both
      CDK4/6 and OCT2 functions.
AB  - Acute kidney injury (AKI) is a potentially fatal syndrome characterized by a
      rapid decline in kidney function caused by ischemic or toxic injury to renal
      tubular cells. The widely used chemotherapy drug cisplatin accumulates
      preferentially in the renal tubular cells and is a frequent cause of drug-induced
      AKI. During the development of AKI the quiescent tubular cells reenter the cell
      cycle. Strategies that block cell-cycle progression ameliorate kidney injury,
      possibly by averting cell division in the presence of extensive DNA damage.
      However, the early signaling events that lead to cell-cycle activation during AKI
      are not known. In the current study, using mouse models of cisplatin
      nephrotoxicity, we show that the G1/S-regulating cyclin-dependent kinase 4/6
      (CDK4/6) pathway is activated in parallel with renal cell-cycle entry but before
      the development of AKI. Targeted inhibition of CDK4/6 pathway by small-molecule
      inhibitors palbociclib (PD-0332991) and ribociclib (LEE011) resulted in
      inhibition of cell-cycle progression, amelioration of kidney injury, and improved
      overall survival. Of additional significance, these compounds were found to be
      potent inhibitors of organic cation transporter 2 (OCT2), which contributes to
      the cellular accumulation of cisplatin and subsequent kidney injury. The unique
      cell-cycle and OCT2-targeting activities of palbociclib and LEE011, combined with
      their potential for clinical translation, support their further exploration as
      therapeutic candidates for prevention of AKI. 

PMID- 25848012
TI  - Structure of CARDS toxin, a unique ADP-ribosylating and vacuolating cytotoxin
      from Mycoplasma pneumoniae.
AB  - Mycoplasma pneumoniae (Mp) infections cause tracheobronchitis and "walking"
      pneumonia, and are linked to asthma and other reactive airway diseases. As part
      of the infectious process, the bacterium expresses a 591-aa virulence factor with
      both mono-ADP ribosyltransferase (mART) and vacuolating activities known as
      Community-Acquired Respiratory Distress Syndrome Toxin (CARDS TX). CARDS TX binds
      to human surfactant protein A and annexin A2 on airway epithelial cells and is
      internalized, leading to a range of pathogenetic events. Here we present the
      structure of CARDS TX, a triangular molecule in which N-terminal mART and C
      terminal tandem beta-trefoil domains associate to form an overall architecture
      distinct from other well-recognized ADP-ribosylating bacterial toxins. We
      demonstrate that CARDS TX binds phosphatidylcholine and sphingomyelin
      specifically over other membrane lipids, and that cell surface binding and
      internalization activities are housed within the C-terminal beta-trefoil domain.
      The results enhance our understanding of Mp pathogenicity and suggest a novel
      avenue for the development of therapies to treat Mp-associated asthma and other
      acute and chronic airway diseases. 

PMID- 25848013
TI  - A modular toolkit to inhibit proline-rich motif-mediated protein-protein
      interactions.
AB  - Small-molecule competitors of protein-protein interactions are urgently needed
      for functional analysis of large-scale genomics and proteomics data. Particularly
      abundant, yet so far undruggable, targets include domains specialized in
      recognizing proline-rich segments, including Src-homology 3 (SH3), WW, GYF, and
      Drosophila enabled (Ena)/vasodilator-stimulated phosphoprotein (VASP) homology 1
      (EVH1) domains. Here, we present a modular strategy to obtain an extendable
      toolkit of chemical fragments (ProMs) designed to replace pairs of conserved
      prolines in recognition motifs. As proof-of-principle, we developed a small,
      selective, peptidomimetic inhibitor of Ena/VASP EVH1 domain interactions. Highly
      invasive MDA MB 231 breast-cancer cells treated with this ligand showed
      displacement of VASP from focal adhesions, as well as from the front of
      lamellipodia, and strongly reduced cell invasion. General applicability of our
      strategy is illustrated by the design of an ErbB4-derived ligand containing two
      ProM-1 fragments, targeting the yes-associated protein 1 (YAP1)-WW domain with a
      fivefold higher affinity. 

PMID- 25848014
TI  - Mimicking the magnetic properties of rare earth elements using superatoms.
AB  - Rare earth elements (REs) consist of a very important group in the periodic table
      that is vital to many modern technologies. The mining process, however, is
      extremely damaging to the environment, making them low yield and very expensive.
      Therefore, mimicking the properties of REs in a superatom framework is especially
      valuable but at the same time, technically challenging and requiring advanced
      concepts about manipulating properties of atom/molecular complexes. Herein, by
      using photoelectron imaging spectroscopy, we provide original idea and direct
      experimental evidence that chosen boron-doped clusters could mimic the magnetic
      characteristics of REs. Specifically, the neutral LaB and NdB clusters are found
      to have similar unpaired electrons and magnetic moments as their isovalent REs
      (namely Nd and Eu, respectively), opening up the great possibility in
      accomplishing rare earth mimicry. Extension of the superatom concept into the
      rare earth group not only further shows the power and advance of this concept but
      also, will stimulate more efforts to explore new superatomic clusters to mimic
      the chemistry of these heavy atoms, which will be of great importance in
      designing novel building blocks in the application of cluster-assembled
      nanomaterials. Additionally, based on these experimental findings, a novel "magic
      boron" counting rule is proposed to estimate the numbers of unpaired electrons in
      diatomic LnB clusters. 

PMID- 25848015
TI  - High-yield hydrogen production from biomass by in vitro metabolic engineering:
      Mixed sugars coutilization and kinetic modeling.
AB  - The use of hydrogen (H2) as a fuel offers enhanced energy conversion efficiency
      and tremendous potential to decrease greenhouse gas emissions, but producing it
      in a distributed, carbon-neutral, low-cost manner requires new technologies.
      Herein we demonstrate the complete conversion of glucose and xylose from plant
      biomass to H2 and CO2 based on an in vitro synthetic enzymatic pathway. Glucose
      and xylose were simultaneously converted to H2 with a yield of two H2 per carbon,
      the maximum possible yield. Parameters of a nonlinear kinetic model were fitted
      with experimental data using a genetic algorithm, and a global sensitivity
      analysis was used to identify the enzymes that have the greatest impact on
      reaction rate and yield. After optimizing enzyme loadings using this model,
      volumetric H2 productivity was increased 3-fold to 32 mmol H2?L(-1)?h(-1). The
      productivity was further enhanced to 54 mmol H2?L(-1)?h(-1) by increasing
      reaction temperature, substrate, and enzyme concentrations--an increase of 67
      fold compared with the initial studies using this method. The production of
      hydrogen from locally produced biomass is a promising means to achieve global
      green energy production.

PMID- 25848016
TI  - Seizure-like activity in a juvenile Angelman syndrome mouse model is attenuated
      by reducing Arc expression.
AB  - Angelman syndrome (AS) is a neurodevelopmental disorder arising from loss-of
      function mutations in the maternally inherited copy of the UBE3A gene, and is
      characterized by an absence of speech, excessive laughter, cognitive delay, motor
      deficits, and seizures. Despite the fact that the symptoms of AS occur in early
      childhood, behavioral characterization of AS mouse models has focused primarily
      on adult phenotypes. In this report we describe juvenile behaviors in AS mice
      that are strain-independent and clinically relevant. We find that young AS mice,
      compared with their wild-type littermates, produce an increased number of
      ultrasonic vocalizations. In addition, young AS mice have defects in motor
      coordination, as well as abnormal brain activity that results in an enhanced
      seizure-like response to an audiogenic challenge. The enhanced seizure-like
      activity, but not the increased ultrasonic vocalizations or motor deficits, is
      rescued in juvenile AS mice by genetically reducing the expression level of the
      activity-regulated cytoskeleton-associated protein, Arc. These findings suggest
      that therapeutic interventions that reduce the level of Arc expression have the
      potential to reverse the seizures associated with AS. In addition, the
      identification of aberrant behaviors in young AS mice may provide clues regarding
      the neural circuit defects that occur in AS and ultimately allow new approaches
      for treating this disorder. 

PMID- 25848017
TI  - Exonuclease TREX1 degrades double-stranded DNA to prevent spontaneous lupus-like
      inflammatory disease.
AB  - The TREX1 gene encodes a potent DNA exonuclease, and mutations in TREX1 cause a
      spectrum of lupus-like autoimmune diseases. Most lupus patients develop
      autoantibodies to double-stranded DNA (dsDNA), but the source of DNA antigen is
      unknown. The TREX1 D18N mutation causes a monogenic, cutaneous form of lupus
      called familial chilblain lupus, and the TREX1 D18N enzyme exhibits dysfunctional
      dsDNA-degrading activity, providing a link between dsDNA degradation and nucleic
      acid-mediated autoimmune disease. We determined the structure of the TREX1 D18N
      protein in complex with dsDNA, revealing how this exonuclease uses a novel DNA
      unwinding mechanism to separate the polynucleotide strands for single-stranded
      DNA (ssDNA) loading into the active site. The TREX1 D18N dsDNA interactions
      coupled with catalytic deficiency explain how this mutant nuclease prevents dsDNA
      degradation. We tested the effects of TREX1 D18N in vivo by replacing the TREX1
      WT gene in mice with the TREX1 D18N allele. The TREX1 D18N mice exhibit systemic
      inflammation, lymphoid hyperplasia, vasculitis, and kidney disease. The observed
      lupus-like inflammatory disease is associated with immune activation, production
      of autoantibodies to dsDNA, and deposition of immune complexes in the kidney.
      Thus, dysfunctional dsDNA degradation by TREX1 D18N induces disease in mice that
      recapitulates many characteristics of human lupus. Failure to clear DNA has long
      been linked to lupus in humans, and these data point to dsDNA as a key substrate
      for TREX1 and a major antigen source in mice with dysfunctional TREX1 enzyme. 

PMID- 25848018
TI  - Fishing amplifies forage fish population collapses.
AB  - Forage fish support the largest fisheries in the world but also play key roles in
      marine food webs by transferring energy from plankton to upper trophic-level
      predators, such as large fish, seabirds, and marine mammals. Fishing can,
      thereby, have far reaching consequences on marine food webs unless safeguards are
      in place to avoid depleting forage fish to dangerously low levels, where
      dependent predators are most vulnerable. However, disentangling the contributions
      of fishing vs. natural processes on population dynamics has been difficult
      because of the sensitivity of these stocks to environmental conditions. Here, we
      overcome this difficulty by collating population time series for forage fish
      populations that account for nearly two-thirds of global catch of forage fish to
      identify the fingerprint of fisheries on their population dynamics. Forage fish
      population collapses shared a set of common and unique characteristics: high
      fishing pressure for several years before collapse, a sharp drop in natural
      population productivity, and a lagged response to reduce fishing pressure. Lagged
      response to natural productivity declines can sharply amplify the magnitude of
      naturally occurring population fluctuations. Finally, we show that the magnitude
      and frequency of collapses are greater than expected from natural productivity
      characteristics and therefore, likely attributed to fishing. The durations of
      collapses, however, were not different from those expected based on natural
      productivity shifts. A risk-based management scheme that reduces fishing when
      populations become scarce would protect forage fish and their predators from
      collapse with little effect on long-term average catches. 

PMID- 25848019
TI  - Mosaic nature of the mitochondrial proteome: Implications for the origin and
      evolution of mitochondria.
AB  - Comparative studies of the mitochondrial proteome have identified a conserved
      core of proteins descended from the alpha-proteobacterial endosymbiont that gave
      rise to the mitochondrion and was the source of the mitochondrial genome in
      contemporary eukaryotes. A surprising result of phylogenetic analyses is the
      relatively small proportion (10-20%) of the mitochondrial proteome displaying a
      clear alpha-proteobacterial ancestry. A large fraction of mitochondrial proteins
      typically has detectable homologs only in other eukaryotes and is presumed to
      represent proteins that emerged specifically within eukaryotes. A further
      significant fraction of the mitochondrial proteome consists of proteins with
      homologs in prokaryotes, but without a robust phylogenetic signal affiliating
      them with specific prokaryotic lineages. The presumptive evolutionary source of
      these proteins is quite different in contending models of mitochondrial origin. 

PMID- 25848021
TI  - Mechanical cloak design by direct lattice transformation.
AB  - Spatial coordinate transformations have helped simplifying mathematical issues
      and solving complex boundary-value problems in physics for decades already. More
      recently, material-parameter transformations have also become an intuitive and
      powerful engineering tool for designing inhomogeneous and anisotropic material
      distributions that perform wanted functions, e.g., invisibility cloaking. A
      necessary mathematical prerequisite for this approach to work is that the
      underlying equations are form invariant with respect to general coordinate
      transformations. Unfortunately, this condition is not fulfilled in elastic-solid
      mechanics for materials that can be described by ordinary elasticity tensors.
      Here, we introduce a different and simpler approach. We directly transform the
      lattice points of a 2D discrete lattice composed of a single constituent
      material, while keeping the properties of the elements connecting the lattice
      points the same. After showing that the approach works in various areas, we focus
      on elastic-solid mechanics. As a demanding example, we cloak a void in an
      effective elastic material with respect to static uniaxial compression.
      Corresponding numerical calculations and experiments on polymer structures made
      by 3D printing are presented. The cloaking quality is quantified by comparing the
      average relative SD of the strain vectors outside of the cloaked void with
      respect to the homogeneous reference lattice. Theory and experiment agree and
      exhibit very good cloaking performance. 

PMID- 25848020
TI  - Effective and lesion-free cutaneous influenza vaccination.
AB  - The current study details efficient lesion-free cutaneous vaccination via vaccine
      delivery into an array of micropores in the skin, instead of bolus injection at a
      single site. Such delivery effectively segregated vaccine-induced inflammation,
      resulting in rapid resolution of the inflammation, provided that distances
      between any two micropores were sufficient. When the inoculation site was treated
      by FDA-approved nonablative fractional laser (NAFL) before insertion of a PR8
      model influenza vaccine-packaged, biodegradable microneedle array (MNs), mice
      displayed vigorous antigen-uptake, eliciting strong Th1-biased immunity. These
      animals were completely protected from homologous viral challenges, and fully or
      partially protected from heterologous H1N1 and H3N2 viral challenges, whereas
      mice receiving MNs alone suffered from severe illnesses or died of similar viral
      challenges. NAFL-mediated adjuvanicity was ascribed primarily to dsDNA and other
      "danger" signals released from laser-damaged skin cells. Thus, mice deficient in
      dsDNA-sensing pathway, but not Toll like receptor (TLR) or inflammasome pathways,
      showed poor responses to NAFL. Importantly, with this novel approach both mice
      and swine exhibited strong protective immunity without incurring any appreciable
      skin irritation, in sharp contrast to the overt skin irritation caused by
      intradermal injections. The effective lesion-free cutaneous vaccination merits
      further clinical studies. 

PMID- 25848022
TI  - GEMM-I riboswitches from Geobacter sense the bacterial second messenger cyclic
      AMP-GMP.
AB  - Cyclic dinucleotides are an expanding class of signaling molecules that control
      many aspects of bacterial physiology. A synthase for cyclic AMP-GMP (cAG, also
      referenced as 3'-5', 3'-5' cGAMP) called DncV is associated with hyperinfectivity
      of Vibrio cholerae but has not been found in many bacteria, raising questions
      about the prevalence and function of cAG signaling. We have discovered that the
      environmental bacterium Geobacter sulfurreducens produces cAG and uses a subset
      of GEMM-I class riboswitches (GEMM-Ib, Genes for the Environment, Membranes, and
      Motility) as specific receptors for cAG. GEMM-Ib riboswitches regulate genes
      associated with extracellular electron transfer; thus cAG signaling may control
      aspects of bacterial electrophysiology. These findings expand the role of cAG
      beyond organisms that harbor DncV and beyond pathogenesis to microbial
      geochemistry, which is important to environmental remediation and microbial fuel
      cell development. Finally, we have developed an RNA-based fluorescent biosensor
      for live-cell imaging of cAG. This selective, genetically encodable biosensor
      will be useful to probe the biochemistry and cell biology of cAG signaling in
      diverse bacteria. 

PMID- 25848023
TI  - Control of bacterial exoelectrogenesis by c-AMP-GMP.
AB  - Major changes in bacterial physiology including biofilm and spore formation
      involve signaling by the cyclic dinucleotides c-di-GMP and c-di-AMP. Recently,
      another second messenger dinucleotide, c-AMP-GMP, was found to control chemotaxis
      and colonization by Vibrio cholerae. We have identified a superregulon of genes
      controlled by c-AMP-GMP in numerous Deltaproteobacteria, including Geobacter
      species that use extracellular insoluble metal oxides as terminal electron
      acceptors. This exoelectrogenic process has been studied for its possible utility
      in energy production and bioremediation. Many genes involved in adhesion, pilin
      formation, and others that are important for exoelectrogenesis are controlled by
      members of a variant riboswitch class that selectively bind c-AMP-GMP. These RNAs
      constitute, to our knowledge, the first known specific receptors for c-AMP-GMP
      and reveal that this molecule is used by many bacteria to control specialized
      physiological processes. 

PMID- 25848024
TI  - Virus decomposition provides an important contribution to benthic deep-sea
      ecosystem functioning.
AB  - Viruses are key biological agents of prokaryotic mortality in the world oceans,
      particularly in deep-sea ecosystems where nearly all of the prokaryotic C
      production is transformed into organic detritus. However, the extent to which the
      decomposition of viral particles (i.e., organic material of viral origin)
      influences the functioning of benthic deep-sea ecosystems remains completely
      unknown. Here, using various independent approaches, we show that in deep-sea
      sediments an important fraction of viruses, once they are released by cell lysis,
      undergo fast decomposition. Virus decomposition rates in deep-sea sediments are
      high even at abyssal depths and are controlled primarily by the extracellular
      enzymatic activities that hydrolyze the proteins of the viral capsids. We
      estimate that on a global scale the decomposition of benthic viruses releases ~37
      50 megatons of C per year and thus represents an important source of labile
      organic compounds in deep-sea ecosystems. Organic material released from
      decomposed viruses is equivalent to 3 +/- 1%, 6 +/- 2%, and 12 +/- 3% of the
      input of photosynthetically produced C, N, and P supplied through particles
      sinking to bathyal/abyssal sediments. Our data indicate that the decomposition of
      viruses provides an important, previously ignored contribution to deep-sea
      ecosystem functioning and has an important role in nutrient cycling within the
      largest ecosystem of the biosphere. 

PMID- 25848025
TI  - Environmental constraints drive the partitioning of the soundscape in fishes.
AB  - The underwater environment is more and more being depicted as particularly noisy,
      and the inventory of calling fishes is continuously increasing. However, it
      currently remains unknown how species share the soundscape and are able to
      communicate without misinterpreting the messages. Different mechanisms of
      interference avoidance have been documented in birds, mammals, and frogs, but
      little is known about interference avoidance in fishes. How fish thus partition
      the soundscape underwater remains unknown, as acoustic communication and its
      organization have never been studied at the level of fish communities. In this
      study, passive acoustic recordings were used to inventory sounds produced in a
      fish community (120 m depth) in an attempt to understand how different species
      partition the acoustic environment. We uncovered an important diversity of fish
      sounds, and 16 of the 37 different sounds recorded were sufficiently abundant to
      use in a quantitative analysis. We show that sonic activity allows a clear
      distinction between a diurnal and a nocturnal group of fishes. Moreover,
      frequencies of signals made during the day overlap, whereas there is a clear
      distinction between the different representatives of the nocturnal callers
      because of a lack of overlap in sound frequency. This first demonstration, to our
      knowledge, of interference avoidance in a fish community can be understood by the
      way sounds are used. In diurnal species, sounds are mostly used to support visual
      display, whereas nocturnal species are generally deprived of visual cues,
      resulting in acoustic constraints being more important. 

PMID- 25848026
TI  - Sorting the wheat from the chaff in dopamine neuron-based cell therapies.

PMID- 25848027
TI  - In vivo characterization of chronic traumatic encephalopathy using [F-18]FDDNP
      PET brain imaging.
AB  - Chronic traumatic encephalopathy (CTE) is an acquired primary tauopathy with a
      variety of cognitive, behavioral, and motor symptoms linked to cumulative brain
      damage sustained from single, episodic, or repetitive traumatic brain injury
      (TBI). No definitive clinical diagnosis for this condition exists. In this work,
      we used [F-18]FDDNP PET to detect brain patterns of neuropathology distribution
      in retired professional American football players with suspected CTE (n = 14) and
      compared results with those of cognitively intact controls (n = 28) and patients
      with Alzheimer's dementia (AD) (n = 24), a disease that has been cognitively
      associated with CTE. [F-18]FDDNP PET imaging results in the retired players
      suggested the presence of neuropathological patterns consistent with models of
      concussion wherein brainstem white matter tracts undergo early axonal damage and
      cumulative axonal injuries along subcortical, limbic, and cortical brain
      circuitries supporting mood, emotions, and behavior. This deposition pattern is
      distinctively different from the progressive pattern of neuropathology [paired
      helical filament (PHF)-tau and amyloid-beta] in AD, which typically begins in the
      medial temporal lobe progressing along the cortical default mode network, with no
      or minimal involvement of subcortical structures. This particular [F-18]FDDNP PET
      imaging pattern in cases of suspected CTE also is primarily consistent with PHF
      tau distribution observed at autopsy in subjects with a history of mild TBI and
      autopsy-confirmed diagnosis of CTE. 

PMID- 25848028
TI  - fMRI of the rod scotoma elucidates cortical rod pathways and implications for
      lesion measurements.
AB  - Are silencing, ectopic shifts, and receptive field (RF) scaling in cortical
      scotoma projection zones (SPZs) the result of long-term reorganization
      (plasticity) or short-term adaptation? Electrophysiological studies of SPZs after
      retinal lesions in animal models remain controversial, because they are unable to
      conclusively answer this question because of limitations of the methodology.
      Here, we used functional MRI (fMRI) visual field mapping through population RF
      (pRF) modeling with moving bar stimuli under photopic and scotopic conditions to
      measure the effects of the rod scotoma in human early visual cortex. As a
      naturally occurring central scotoma, it has a large cortical representation, is
      free of traumatic lesion complications, is completely reversible, and has not
      reorganized under normal conditions (but can as seen in rod monochromats). We
      found that the pRFs overlapping the SPZ in V1, V2, V3, hV4, and VO-1 generally
      (i) reduced their blood oxygen level-dependent signal coherence and (ii) shifted
      their pRFs more eccentric but (iii) scaled their pRF sizes in variable ways.
      Thus, silencing, ectopic shifts, and pRF scaling in SPZs are not unique
      identifiers of cortical reorganization; rather, they can be the expected result
      of short-term adaptation. However, are there differences between rod and cone
      signals in V1, V2, V3, hV4, and VO-1? We did not find differences for all five
      maps in more peripheral eccentricities outside of rod scotoma influence in
      coherence, eccentricity representation, or pRF size. Thus, rod and cone signals
      seem to be processed similarly in cortex. 

PMID- 25848029
TI  - Panoramic view of a superfamily of phosphatases through substrate profiling.
AB  - Large-scale activity profiling of enzyme superfamilies provides information about
      cellular functions as well as the intrinsic binding capabilities of conserved
      folds. Herein, the functional space of the ubiquitous haloalkanoate dehalogenase
      superfamily (HADSF) was revealed by screening a customized substrate library
      against >200 enzymes from representative prokaryotic species, enabling inferred
      annotation of ~35% of the HADSF. An extremely high level of substrate ambiguity
      was revealed, with the majority of HADSF enzymes using more than five substrates.
      Substrate profiling allowed assignment of function to previously unannotated
      enzymes with known structure, uncovered potential new pathways, and identified
      iso-functional orthologs from evolutionarily distant taxonomic groups.
      Intriguingly, the HADSF subfamily having the least structural elaboration of the
      Rossmann fold catalytic domain was the most specific, consistent with the concept
      that domain insertions drive the evolution of new functions and that the broad
      specificity observed in HADSF may be a relic of this process. 

PMID- 25848030
TI  - Cell-autonomous activation of Hedgehog signaling inhibits brown adipose tissue
      development.
AB  - Although recent studies have shown that brown adipose tissue (BAT) arises from
      progenitor cells that also give rise to skeletal muscle, the developmental
      signals that control the formation of BAT remain largely unknown. Here, we show
      that brown preadipocytes possess primary cilia and can respond to Hedgehog (Hh)
      signaling. Furthermore, cell-autonomous activation of Hh signaling blocks early
      brown-preadipocyte differentiation, inhibits BAT formation in vivo, and results
      in replacement of neck BAT with poorly differentiated skeletal muscle. Finally,
      we show that Hh signaling inhibits BAT formation partially through up-regulation
      of chicken ovalbumin upstream promoter transcription factor II (COUP-TFII). Taken
      together, our studies uncover a previously unidentified role for Hh as an
      inhibitor of BAT development. 

PMID- 25848031
TI  - Adaptive evolution toward larger size in mammals.
AB  - The notion that large body size confers some intrinsic advantage to biological
      species has been debated for centuries. Using a phylogenetic statistical approach
      that allows the rate of body size evolution to vary across a phylogeny, we find a
      long-term directional bias toward increasing size in the mammals. This pattern
      holds separately in 10 of 11 orders for which sufficient data are available and
      arises from a tendency for accelerated rates of evolution to produce increases,
      but not decreases, in size. On a branch-by-branch basis, increases in body size
      have been more than twice as likely as decreases, yielding what amounts to
      millions and millions of years of rapid and repeated increases in size away from
      the small ancestral mammal. These results are the first evidence, to our
      knowledge, from extant species that are compatible with Cope's rule: the pattern
      of body size increase through time observed in the mammalian fossil record. We
      show that this pattern is unlikely to be explained by several nonadaptive
      mechanisms for increasing size and most likely represents repeated responses to
      new selective circumstances. By demonstrating that it is possible to uncover
      ancient evolutionary trends from a combination of a phylogeny and appropriate
      statistical models, we illustrate how data from extant species can complement
      paleontological accounts of evolutionary history, opening up new avenues of
      investigation for both. 

PMID- 25848032
TI  - Identity-specific coding of future rewards in the human orbitofrontal cortex.
AB  - Nervous systems must encode information about the identity of expected outcomes
      to make adaptive decisions. However, the neural mechanisms underlying identity
      specific value signaling remain poorly understood. By manipulating the value and
      identity of appetizing food odors in a pattern-based imaging paradigm of human
      classical conditioning, we were able to identify dissociable predictive
      representations of identity-specific reward in orbitofrontal cortex (OFC) and
      identity-general reward in ventromedial prefrontal cortex (vmPFC). Reward-related
      functional coupling between OFC and olfactory (piriform) cortex and between vmPFC
      and amygdala revealed parallel pathways that support identity-specific and 
      general predictive signaling. The demonstration of identity-specific value
      representations in OFC highlights a role for this region in model-based behavior
      and reveals mechanisms by which appetitive behavior can go awry. 

PMID- 25848033
TI  - Sterile inflammation in the spleen during atherosclerosis provides oxidation
      specific epitopes that induce a protective B-cell response.
AB  - The B-cell response in atherosclerosis is directed toward oxidation-specific
      epitopes such as phosphorylcholine (PC) that arise during disease-driven
      oxidation of self-antigens. PC-bearing antigens have been used to induce
      atheroprotective antibodies against modified low-density lipoproteins (oxLDL),
      leading to plaque reduction. Previous studies have found that B-cell transfer
      from aged atherosclerotic mice confers protection to young mice, but the
      mechanism is unknown. Here, we dissected the atheroprotective response in the
      spleen and found an ongoing germinal center reaction, accumulation of antibody
      forming cells, and inflammasome activation in apolipoprotein E-deficient mice
      (Apoe(-/-)). Specific B-cell clone expansion involved the heavy chain variable
      region (Vh) 5 and Vh7 B-cell receptor families that harbor anti-PC reactivity.
      oxLDL also accumulated in the spleen. To investigate whether protection could be
      induced by self-antigens alone, we injected apoptotic cells that carry the same
      oxidation-specific epitopes as oxLDL. This treatment reduced serum cholesterol
      and inhibited the development of atherosclerosis in a B-cell-dependent manner.
      Thus, we conclude that the spleen harbors a protective B-cell response that is
      initiated in atherosclerosis through sterile inflammation. These data highlight
      the importance of the spleen in atherosclerosis-associated immunity. 

PMID- 25848034
TI  - Alternative approach to protein structure prediction based on sequential
      similarity of physical properties.
AB  - The relationship between protein sequence and structure arises entirely from
      amino acid physical properties. An alternative method is therefore proposed to
      identify homologs in which residue equivalence is based exclusively on the
      pairwise physical property similarities of sequences. This approach, the property
      factor method (PFM), is entirely different from those in current use. A
      comparison is made between our method and PSI BLAST. We demonstrate that
      traditionally defined sequence similarity can be very low for pairs of sequences
      (which therefore cannot be identified using PSI BLAST), but similarity of
      physical property distributions results in almost identical 3D structures. The
      performance of PFM is shown to be better than that of PSI BLAST when sequence
      matching is comparable, based on a comparison using targets from CASP10 (89
      targets) and CASP11 (51 targets). It is also shown that PFM outperforms PSI BLAST
      in informatically challenging targets. 

PMID- 25848036
TI  - Profile of Melinda a. Zeder.

PMID- 25848035
TI  - Base-enhanced catalytic water oxidation by a carboxylate-bipyridine Ru(II)
      complex.
AB  - In aqueous solution above pH 2.4 with 4% (vol/vol) CH3CN, the complex
      [Ru(II)(bda)(isoq)2] (bda is 2,2'-bipyridine-6,6'-dicarboxylate; isoq is
      isoquinoline) exists as the open-arm chelate, [Ru(II)(CO2-bpy-CO2(
      ))(isoq)2(NCCH3)], as shown by (1)H and (13)C-NMR, X-ray crystallography, and pH
      titrations. Rates of water oxidation with the open-arm chelate are remarkably
      enhanced by added proton acceptor bases, as measured by cyclic voltammetry (CV).
      In 1.0 M PO4(3-), the calculated half-time for water oxidation is ~7 MUs. The key
      to the rate accelerations with added bases is direct involvement of the buffer
      base in either atom-proton transfer (APT) or concerted electron-proton transfer
      (EPT) pathways.

PMID- 25848037
TI  - Architecture of the cerebral cortical association connectome underlying
      cognition.
AB  - Cognition presumably emerges from neural activity in the network of association
      connections between cortical regions that is modulated by inputs from sensory and
      state systems and directs voluntary behavior by outputs to the motor system. To
      reveal global architectural features of the cortical association connectome,
      network analysis was performed on >16,000 reports of histologically defined
      axonal connections between cortical regions in rat. The network analysis reveals
      an organization into four asymmetrically interconnected modules involving the
      entire cortex in a topographic and topologic core-shell arrangement. There is
      also a topographically continuous U-shaped band of cortical areas that are highly
      connected with each other as well as with the rest of the cortex extending
      through all four modules, with the temporal pole of this band (entorhinal area)
      having the most cortical association connections of all. These results provide a
      starting point for compiling a mammalian nervous system connectome that could
      ultimately reveal novel correlations between genome-wide association studies and
      connectome-wide association studies, leading to new insights into the cellular
      architecture supporting cognition. 

PMID- 25848038
TI  - Endothelin-1 critically influences cardiac function via superoxide-MMP9 cascade.
AB  - We have generated low-expressing and high-expressing endothelin-1 genes (L and H)
      and have bred mice with four levels of expression: L/L, ~20%; L/+, ~65%; +/+
      (wild type), 100%; and H/+, ~350%. The hypomorphic L allele can be
      spatiotemporally switched to the hypermorphic H allele by Cre-loxP recombination.
      Young adult L/L and L/+ mice have dilated cardiomyopathy, hypertension, and
      increased plasma volumes, together with increased ventricular superoxide levels,
      increased matrix metalloproteinase 9 (Mmp9) expression, and reduced ventricular
      stiffness. H/+ mice have decreased plasma volumes and significantly heavy stiff
      hearts. Global or cardiomyocyte-specific switching expression from L to H
      normalized the abnormalities already present in young adult L/L mice. An
      epithelial sodium channel antagonist normalized plasma volume and blood pressure,
      but only partially corrected the cardiomyopathy. A superoxide dismutase mimetic
      made superoxide levels subnormal, reduced Mmp9 overexpression, and substantially
      improved cardiac function. Genetic absence of Mmp9 also improved cardiac
      function, but increased superoxide remained. We conclude that endothelin-1 is
      critical for maintaining normal contractile function, for controlling superoxide
      and Mmp9 levels, and for ensuring that the myocardium has sufficient collagen to
      prevent overstretching. Even a modest (~35%) decrease in endothelin-1 gene (Edn1)
      expression is sufficient to cause cardiac dysfunction. 

PMID- 25848039
TI  - Acoustic separation of circulating tumor cells.
AB  - Circulating tumor cells (CTCs) are important targets for cancer biology studies.
      To further elucidate the role of CTCs in cancer metastasis and prognosis,
      effective methods for isolating extremely rare tumor cells from peripheral blood
      must be developed. Acoustic-based methods, which are known to preserve the
      integrity, functionality, and viability of biological cells using label-free and
      contact-free sorting, have thus far not been successfully developed to isolate
      rare CTCs using clinical samples from cancer patients owing to technical
      constraints, insufficient throughput, and lack of long-term device stability. In
      this work, we demonstrate the development of an acoustic-based microfluidic
      device that is capable of high-throughput separation of CTCs from peripheral
      blood samples obtained from cancer patients. Our method uses tilted-angle
      standing surface acoustic waves. Parametric numerical simulations were performed
      to design optimum device geometry, tilt angle, and cell throughput that is more
      than 20 times higher than previously possible for such devices. We first
      validated the capability of this device by successfully separating low
      concentrations (~100 cells/mL) of a variety of cancer cells from cell culture
      lines from WBCs with a recovery rate better than 83%. We then demonstrated the
      isolation of CTCs in blood samples obtained from patients with breast cancer. Our
      acoustic-based separation method thus offers the potential to serve as an
      invaluable supplemental tool in cancer research, diagnostics, drug efficacy
      assessment, and therapeutics owing to its excellent biocompatibility, simple
      design, and label-free automated operation while offering the capability to
      isolate rare CTCs in a viable state. 

PMID- 25848040
TI  - Ovary ecdysteroidogenic hormone requires a receptor tyrosine kinase to activate
      egg formation in the mosquito Aedes aegypti.
AB  - Mosquitoes are major disease vectors because most species must feed on blood from
      a vertebrate host to produce eggs. Blood feeding by the vector mosquito Aedes
      aegypti triggers the release of two neurohormones, ovary ecdysteroidogenic
      hormone (OEH) and insulin-like peptides (ILPs), which activate multiple processes
      required for egg formation. ILPs function by binding to the insulin receptor,
      which activates downstream components in the canonical insulin signaling pathway.
      OEH in contrast belongs to a neuropeptide family called neuroparsins, whose
      receptor is unknown. Here we demonstrate that a previously orphanized receptor
      tyrosine kinase (RTK) from A. aegypti encoded by the gene AAEL001915 is an OEH
      receptor. Phylogenetic studies indicated that the protein encoded by this gene,
      designated AAEL001915, belongs to a clade of RTKs related to the insulin
      receptor, which are distinguished by an extracellular Venus flytrap module.
      Knockdown of AAEL001915 by RNAi disabled OEH-mediated egg formation in A.
      aegypti. AAEL001915 was primarily detected in the mosquito ovary in association
      with follicular epithelial cells. Both monomeric and dimeric AAEL001915 were
      detected in mosquito ovaries and transfected Drosophila S2 cells. Functional
      assays further indicated that OEH bound to dimeric AAEL001915, which resulted in
      downstream phosphorylation of Ak strain transforming factor (Akt). We hypothesize
      that orthologs of AAEL001915 in other insects are neuroparsin receptors. 

PMID- 25848041
TI  - Effect of neighborhood stigma on economic transactions.
AB  - The hypothesis of neighborhood stigma predicts that individuals who reside in
      areas known for high crime, poverty, disorder, and/or racial isolation embody the
      negative characteristics attributed to their communities and experience suspicion
      and mistrust in their interactions with strangers. This article provides an
      experimental test of whether neighborhood stigma affects individuals in one
      domain of social life: economic transactions. To evaluate the neighborhood stigma
      hypothesis, this study adopts an audit design in a locally organized, online
      classified market, using advertisements for used iPhones and randomly
      manipulating the neighborhood of the seller. The primary outcome under study is
      the number of responses generated by sellers from disadvantaged relative to
      advantaged neighborhoods. Advertisements from disadvantaged neighborhoods
      received significantly fewer responses than advertisements from advantaged
      neighborhoods. Results provide robust evidence that individuals from
      disadvantaged neighborhoods bear a stigma that influences their prospects in
      economic exchanges. The stigma is greater for advertisements originating from
      disadvantaged neighborhoods where the majority of residents are black. This
      evidence reveals that residence in a disadvantaged neighborhood not only affects
      individuals through mechanisms involving economic resources, institutional
      quality, and social networks but also affects residents through the perceptions
      of others. 

PMID- 25848043
TI  - Metallic lead nanospheres discovered in ancient zircons.
AB  - Zircon (ZrSiO4) is the most commonly used geochronometer, preserving age and
      geochemical information through a wide range of geological processes. However,
      zircon U-Pb geochronology can be affected by redistribution of radiogenic Pb,
      which is incompatible in the crystal structure. This phenomenon is particularly
      common in zircon that has experienced ultra-high temperature metamorphism, where
      ion imaging has revealed submicrometer domains that are sufficiently
      heterogeneously distributed to severely perturb ages, in some cases yielding
      apparent Hadean (>4 Ga) ages from younger zircons. Documenting the composition
      and mineralogy of these Pb-enriched domains is essential for understanding the
      processes of Pb redistribution in zircon and its effects on geochronology. Using
      high-resolution scanning transmission electron microscopy, we show that Pb-rich
      domains previously identified in zircons from East Antarctic granulites are 5-30
      nm nanospheres of metallic Pb. They are randomly distributed with respect to
      zircon crystallinity, and their association with a Ti- and Al-rich silica melt
      suggests that they represent melt inclusions generated during ultra-high
      temperature metamorphism. Metallic Pb is exceedingly rare in nature and
      previously has not been reported in association with high-grade metamorphism.
      Formation of these metallic nanospheres within annealed zircon effectively halts
      the loss of radiogenic Pb from zircon. Both the redistribution and phase
      separation of radiogenic Pb in this manner can compromise the precision and
      accuracy of U-Pb ages obtained by high spatial resolution methods. 

PMID- 25848042
TI  - Balance between cell-substrate adhesion and myosin contraction determines the
      frequency of motility initiation in fish keratocytes.
AB  - Cells are dynamic systems capable of spontaneously switching among stable states.
      One striking example of this is spontaneous symmetry breaking and motility
      initiation in fish epithelial keratocytes. Although the biochemical and
      mechanical mechanisms that control steady-state migration in these cells have
      been well characterized, the mechanisms underlying symmetry breaking are less
      well understood. In this work, we have combined experimental manipulations of
      cell-substrate adhesion strength and myosin activity, traction force
      measurements, and mathematical modeling to develop a comprehensive mechanical
      model for symmetry breaking and motility initiation in fish epithelial
      keratocytes. Our results suggest that stochastic fluctuations in adhesion
      strength and myosin localization drive actin network flow rates in the
      prospective cell rear above a critical threshold. Above this threshold, high
      actin flow rates induce a nonlinear switch in adhesion strength, locally
      switching adhesions from gripping to slipping and further accelerating actin flow
      in the prospective cell rear, resulting in rear retraction and motility
      initiation. We further show, both experimentally and with model simulations, that
      the global levels of adhesion strength and myosin activity control the stability
      of the stationary state: The frequency of symmetry breaking decreases with
      increasing adhesion strength and increases with increasing myosin contraction.
      Thus, the relative strengths of two opposing mechanical forces--contractility and
      cell-substrate adhesion--determine the likelihood of spontaneous symmetry
      breaking and motility initiation.

PMID- 25848044
TI  - Stoichiometric control of DNA-grafted colloid self-assembly.
AB  - There has been considerable interest in understanding the self-assembly of DNA
      grafted nanoparticles into different crystal structures, e.g., CsCl, AlB2, and
      Cr3Si. Although there are important exceptions, a generally accepted view is that
      the right stoichiometry of the two building block colloids needs to be mixed to
      form the desired crystal structure. To incisively probe this issue, we combine
      experiments and theory on a series of DNA-grafted nanoparticles at varying
      stoichiometries, including noninteger values. We show that stoichiometry can
      couple with the geometries of the building blocks to tune the resulting
      equilibrium crystal morphology. As a concrete example, a stoichiometric ratio of
      3:1 typically results in the Cr3Si structure. However, AlB2 can form when
      appropriate building blocks are used so that the AlB2 standard-state free energy
      is low enough to overcome the entropic preference for Cr3Si. These situations can
      also lead to an undesirable phase coexistence between crystal polymorphs. Thus,
      whereas stoichiometry can be a powerful handle for direct control of lattice
      formation, care must be taken in its design and selection to avoid polymorph
      coexistence. 

PMID- 25848045
TI  - Small molecule-induced oxidation of protein disulfide isomerase is
      neuroprotective.
AB  - Protein disulfide isomerase (PDI) is a chaperone protein in the endoplasmic
      reticulum that is up-regulated in mouse models of, and brains of patients with,
      neurodegenerative diseases involving protein misfolding. PDI's role in these
      diseases, however, is not fully understood. Here, we report the discovery of a
      reversible, neuroprotective lead optimized compound (LOC)14, that acts as a
      modulator of PDI. LOC14 was identified using a high-throughput screen of ~10,000
      lead-optimized compounds for potent rescue of viability of PC12 cells expressing
      mutant huntingtin protein, followed by an evaluation of compounds on PDI
      reductase activity in an in vitro screen. Isothermal titration calorimetry and
      fluorescence experiments revealed that binding to PDI was reversible with a Kd of
      62 nM, suggesting LOC14 to be the most potent PDI inhibitor reported to date.
      Using 2D heteronuclear single quantum correlation NMR experiments, we were able
      to map the binding site of LOC14 as being adjacent to the active site and to
      observe that binding of LOC14 forces PDI to adopt an oxidized conformation.
      Furthermore, we found that LOC14-induced oxidation of PDI has a neuroprotective
      effect not only in cell culture, but also in corticostriatal brain slice
      cultures. LOC14 exhibited high stability in mouse liver microsomes and blood
      plasma, low intrinsic microsome clearance, and low plasma-protein binding. These
      results suggest that LOC14 is a promising lead compound to evaluate the potential
      therapeutic effects of modulating PDI in animal models of disease. 

PMID- 25848046
TI  - Evolution of the rapidly mutating human salivary agglutinin gene (DMBT1) and
      population subsistence strategy.
AB  - The dietary change resulting from the domestication of plant and animal species
      and development of agriculture at different locations across the world was one of
      the most significant changes in human evolution. An increase in dietary
      carbohydrates caused an increase in dental caries following the development of
      agriculture, mediated by the cariogenic oral bacterium Streptococcus mutans.
      Salivary agglutinin [SAG, encoded by the deleted in malignant brain tumors 1
      (DMBT1) gene] is an innate immune receptor glycoprotein that binds a variety of
      bacteria and viruses, and mediates attachment of S. mutans to hydroxyapatite on
      the surface of the tooth. In this study we show that multiallelic copy number
      variation (CNV) within DMBT1 is extensive across all populations and is predicted
      to result in between 7-20 scavenger-receptor cysteine-rich (SRCR) domains within
      each SAG molecule. Direct observation of de novo mutation in multigeneration
      families suggests these CNVs have a very high mutation rate for a protein-coding
      locus, with a mutation rate of up to 5% per gamete. Given that the SRCR domains
      bind S. mutans and hydroxyapatite in the tooth, we investigated the association
      of sequence diversity at the SAG-binding gene of S. mutans, and DMBT1 CNV.
      Furthermore, we show that DMBT1 CNV is also associated with a history of
      agriculture across global populations, suggesting that dietary change as a result
      of agriculture has shaped the pattern of CNV at DMBT1, and that the DMBT1-S.
      mutans interaction is a promising model of host-pathogen-culture coevolution in
      humans. 

PMID- 25848047
TI  - Compromised peroxisomes in idiopathic pulmonary fibrosis, a vicious cycle
      inducing a higher fibrotic response via TGF-beta signaling.
AB  - Idiopathic pulmonary fibrosis (IPF) is a devastating disease, and its pathogenic
      mechanisms remain incompletely understood. Peroxisomes are known to be important
      in ROS and proinflammatory lipid degradation, and their deficiency induces liver
      fibrosis. However, altered peroxisome functions in IPF pathogenesis have never
      been investigated. By comparing peroxisome-related protein and gene expression in
      lung tissue and isolated lung fibroblasts between human control and IPF patients,
      we found that IPF lungs exhibited a significant down-regulation of peroxisomal
      biogenesis and metabolism (e.g., PEX13p and acyl-CoA oxidase 1). Moreover, in
      vivo the bleomycin-induced down-regulation of peroxisomes was abrogated in
      transforming growth factor beta (TGF-beta) receptor II knockout mice indicating a
      role for TGF-beta signaling in the regulation of peroxisomes. Furthermore, in
      vitro treatment of IPF fibroblasts with the profibrotic factors TGF-beta1 or
      tumor necrosis factor alpha (TNF-alpha) was found to down-regulate peroxisomes
      via the AP-1 signaling pathway. Therefore, the molecular mechanisms by which
      reduced peroxisomal functions contribute to enhanced fibrosis were further
      studied. Direct down-regulation of PEX13 by RNAi induced the activation of Smad
      dependent TGF-beta signaling accompanied by increased ROS production and resulted
      in the release of cytokines (e.g., IL-6, TGF-beta) and excessive production of
      collagen I and III. In contrast, treatment of fibroblasts with ciprofibrate or
      WY14643, PPAR-alpha activators, led to peroxisome proliferation and reduced the
      TGF-beta-induced myofibroblast differentiation and collagen protein in IPF cells.
      Taken together, our findings suggest that compromised peroxisome activity might
      play an important role in the molecular pathogenesis of IPF and fibrosis
      progression, possibly by exacerbating pulmonary inflammation and intensifying the
      fibrotic response in the patients. 

PMID- 25848048
TI  - Continental-level biodiversity collapse.

PMID- 25848049
TI  - Stochastic induction of persister cells by HipA through (p)ppGpp-mediated
      activation of mRNA endonucleases.
AB  - The model organism Escherichia coli codes for at least 11 type II toxin-antitoxin
      (TA) modules, all implicated in bacterial persistence (multidrug tolerance). Ten
      of these encode messenger RNA endonucleases (mRNases) inhibiting translation by
      catalytic degradation of mRNA, and the 11th module, hipBA, encodes HipA (high
      persister protein A) kinase, which inhibits glutamyl tRNA synthetase (GltX). In
      turn, inhibition of GltX inhibits translation and induces the stringent response
      and persistence. Previously, we presented strong support for a model proposing
      (p)ppGpp (guanosine tetra and penta-phosphate) as the master regulator of
      persistence. Stochastic variation of [(p)ppGpp] in single cells induced TA
      encoded mRNases via a pathway involving polyphosphate and Lon protease.
      Polyphosphate activated Lon to degrade all known type II antitoxins of E. coli.
      In turn, the activated mRNases induced persistence and multidrug tolerance.
      However, even though it was known that activation of HipA stimulated (p)ppGpp
      synthesis, our model did not explain how hipBA induced persistence. Here we show
      that, in support of and consistent with our initial model, HipA-induced
      persistence depends not only on (p)ppGpp but also on the 10 mRNase-encoding TA
      modules, Lon protease, and polyphosphate. Importantly, observations with single
      cells convincingly show that the high level of (p)ppGpp caused by activation of
      HipA does not induce persistence in the absence of TA-encoded mRNases. Thus, slow
      growth per se does not induce persistence in the absence of TA-encoded toxins,
      placing these genes as central effectors of bacterial persistence. 

PMID- 25848050
TI  - Information flow between interacting human brains: Identification, validation,
      and relationship to social expertise.
AB  - Social interactions are fundamental for human behavior, but the quantification of
      their neural underpinnings remains challenging. Here, we used hyperscanning
      functional MRI (fMRI) to study information flow between brains of human dyads
      during real-time social interaction in a joint attention paradigm. In a hardware
      setup enabling immersive audiovisual interaction of subjects in linked fMRI
      scanners, we characterize cross-brain connectivity components that are unique to
      interacting individuals, identifying information flow between the sender's and
      receiver's temporoparietal junction. We replicate these findings in an
      independent sample and validate our methods by demonstrating that cross-brain
      connectivity relates to a key real-world measure of social behavior. Together,
      our findings support a central role of human-specific cortical areas in the brain
      dynamics of dyadic interactions and provide an approach for the noninvasive
      examination of the neural basis of healthy and disturbed human social behavior
      with minimal a priori assumptions. 

PMID- 25848051
TI  - Pain-enhancing mechanism through interaction between TRPV1 and anoctamin 1 in
      sensory neurons.
AB  - The capsaicin receptor transient receptor potential cation channel vanilloid 1
      (TRPV1) is activated by various noxious stimuli, and the stimuli are converted
      into electrical signals in primary sensory neurons. It is believed that cation
      influx through TRPV1 causes depolarization, leading to the activation of voltage
      gated sodium channels, followed by the generation of action potential. Here we
      report that the capsaicin-evoked action potential could be induced by two
      components: a cation influx-mediated depolarization caused by TRPV1 activation
      and a subsequent anion efflux-mediated depolarization via activation of anoctamin
      1 (ANO1), a calcium-activated chloride channel, resulting from the entry of
      calcium through TRPV1. The interaction between TRPV1 and ANO1 is based on their
      physical binding. Capsaicin activated the chloride currents in an extracellular
      calcium-dependent manner in HEK293T cells expressing TRPV1 and ANO1. Similarly,
      in mouse dorsal root ganglion neurons, capsaicin-activated inward currents were
      inhibited significantly by a specific ANO1 antagonist, T16Ainh-A01 (A01), in the
      presence of a high concentration of EGTA but not in the presence of BAPTA [1,2
      bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid]. The generation of a
      capsaicin-evoked action potential also was inhibited by A01. Furthermore, pain
      related behaviors in mice treated with capsaicin, but not with alphabeta
      methylene ATP, were reduced significantly by the concomitant administration of
      A01. These results indicate that TRPV1-ANO1 interaction is a significant pain
      enhancing mechanism in the peripheral nervous system. 

PMID- 25848052
TI  - FtsZ filament capping by MciZ, a developmental regulator of bacterial division.
AB  - Cytoskeletal structures are dynamically remodeled with the aid of regulatory
      proteins. FtsZ (filamentation temperature-sensitive Z) is the bacterial homolog
      of tubulin that polymerizes into rings localized to cell-division sites, and the
      constriction of these rings drives cytokinesis. Here we investigate the mechanism
      by which the Bacillus subtilis cell-division inhibitor, MciZ (mother cell
      inhibitor of FtsZ), blocks assembly of FtsZ. The X-ray crystal structure reveals
      that MciZ binds to the C-terminal polymerization interface of FtsZ, the
      equivalent of the minus end of tubulin. Using in vivo and in vitro assays and
      microscopy, we show that MciZ, at substoichiometric levels to FtsZ, causes
      shortening of protofilaments and blocks the assembly of higher-order FtsZ
      structures. The findings demonstrate an unanticipated capping-based regulatory
      mechanism for FtsZ. 

PMID- 25848053
TI  - General and condition-specific essential functions of Pseudomonas aeruginosa.
AB  - The essential functions of a bacterial pathogen reflect the most basic processes
      required for its viability and growth, and represent potential therapeutic
      targets. Most screens for essential genes have assayed a single condition--growth
      in a rich undefined medium--and thus have not distinguished genes that are
      generally essential from those that are specific to this particular condition. To
      help define these classes for Pseudomonas aeruginosa, we identified genes
      required for growth on six different media, including a medium made from cystic
      fibrosis patient sputum. The analysis used the Tn-seq circle method to achieve
      high genome coverage and analyzed more than 1,000,000 unique insertion positions
      (an average of one insertion every 6.0 bp). We identified 352 general and 199
      condition-specific essential genes. A subset of assignments was verified in
      individual strains with regulated expression alleles. The profile of essential
      genes revealed that, compared with Escherichia coli, P. aeruginosa is highly
      vulnerable to mutations disrupting central carbon-energy metabolism and reactive
      oxygen defenses. These vulnerabilities may arise from the stripped-down
      architecture of the organism's carbohydrate utilization pathways and its reliance
      on respiration for energy generation. The essential function profile thus
      provides fundamental insights into P. aeruginosa physiology as well as
      identifying candidate targets for new antibacterial agents.

PMID- 25848054
TI  - Productive mRNA stem loop-mediated transcriptional slippage: Crucial features in
      common with intrinsic terminators.
AB  - Escherichia coli and yeast DNA-dependent RNA polymerases are shown to mediate
      efficient nascent transcript stem loop formation-dependent RNA-DNA hybrid
      realignment. The realignment was discovered on the heteropolymeric sequence T5C5
      and yields transcripts lacking a C residue within a corresponding U5C4. The
      sequence studied is derived from a Roseiflexus insertion sequence (IS) element
      where the resulting transcriptional slippage is required for transposase
      synthesis. The stability of the RNA structure, the proximity of the stem loop to
      the slippage site, the length and composition of the slippage site motif, and the
      identity of its 3' adjacent nucleotides (nt) are crucial for transcripts lacking
      a single C. In many respects, the RNA structure requirements for this slippage
      resemble those for hairpin-dependent transcription termination. In a purified in
      vitro system, the slippage efficiency ranges from 5% to 75% depending on the
      concentration ratios of the nucleotides specified by the slippage sequence and
      the 3' nt context. The only previous proposal of stem loop mediated slippage,
      which was in Ebola virus expression, was based on incorrect data interpretation.
      We propose a mechanical slippage model involving the RNAP translocation state as
      the main motor in slippage directionality and efficiency. It is distinct from
      previously described models, including the one proposed for paramyxovirus, where
      following random movement efficiency is mainly dependent on the stability of the
      new realigned hybrid. In broadening the scope for utilization of transcription
      slippage for gene expression, the stimulatory structure provides parallels with
      programmed ribosomal frameshifting at the translation level. 

PMID- 25848055
TI  - Sall4-Gli3 system in early limb progenitors is essential for the development of
      limb skeletal elements.
AB  - Limb skeletal elements originate from the limb progenitor cells, which undergo
      expansion and patterning to develop each skeletal element. Posterior-distal
      skeletal elements, such as the ulna/fibula and posterior digits develop in a
      Sonic hedgehog (Shh)-dependent manner. However, it is poorly understood how
      anterior-proximal elements, such as the humerus/femur, the radius/tibia and the
      anterior digits, are developed. Here we show that the zinc finger factors Sall4
      and Gli3 cooperate for proper development of the anterior-proximal skeletal
      elements and also function upstream of Shh-dependent posterior skeletal element
      development. Conditional inactivation of Sall4 in the mesoderm before limb
      outgrowth caused severe defects in the anterior-proximal skeletal elements in the
      hindlimb. We found that Gli3 expression is reduced in Sall4 mutant hindlimbs, but
      not in forelimbs. This reduction caused posteriorization of nascent hindlimb
      buds, which is correlated with a loss of anterior digits. In proximal
      development, Sall4 integrates Gli3 and the Plzf-Hox system, in addition to
      proliferative expansion of cells in the mesenchymal core of nascent hindlimb
      buds. Whereas forelimbs developed normally in Sall4 mutants, further genetic
      analysis identified that the Sall4-Gli3 system is a common regulator of the early
      limb progenitor cells in both forelimbs and hindlimbs. The Sall4-Gli3 system also
      functions upstream of the Shh-expressing ZPA and the Fgf8-expressing AER in fore-
      and hindlimbs. Therefore, our study identified a critical role of the Sall4-Gli3
      system at the early steps of limb development for proper development of the
      appendicular skeletal elements. 

PMID- 25848056
TI  - NADPH oxidase DUOX1 promotes long-term persistence of oxidative stress after an
      exposure to irradiation.
AB  - Ionizing radiation (IR) causes not only acute tissue damage, but also late
      effects in several cell generations after the initial exposure. The thyroid gland
      is one of the most sensitive organs to the carcinogenic effects of IR, and we
      have recently highlighted that an oxidative stress is responsible for the
      chromosomal rearrangements found in radio-induced papillary thyroid carcinoma.
      Using both a human thyroid cell line and primary thyrocytes, we investigated the
      mechanism by which IR induces the generation of reactive oxygen species (ROS)
      several days after irradiation. We focused on NADPH oxidases, which are
      specialized ROS-generating enzymes known as NOX/DUOX. Our results show that IR
      induces delayed NADPH oxidase DUOX1-dependent H2O2 production in a dose-dependent
      manner, which is sustained for several days. We report that p38 MAPK, activated
      after IR, increased DUOX1 via IL-13 expression, leading to persistent DNA damage
      and growth arrest. Pretreatment of cells with catalase, a scavenger of H2O2, or
      DUOX1 down-regulation by siRNA abrogated IR-induced DNA damage. Analysis of human
      thyroid tissues showed that DUOX1 is elevated not only in human radio-induced
      thyroid tumors, but also in sporadic thyroid tumors. Taken together, our data
      reveal a key role of DUOX1-dependent H2O2 production in long-term persistent
      radio-induced DNA damage. Our data also show that DUOX1-dependent H2O2
      production, which induces DNA double-strand breaks, can cause genomic instability
      and promote the generation of neoplastic cells through its mutagenic effect. 

PMID- 25848057
TI  - Visualized macrophage dynamics and significance of S100A8 in obese fat.
AB  - Chronic low-grade inflammation of adipose tissue plays a crucial role in the
      pathophysiology of obesity. Immunohistological microscopic analysis in obese fat
      tissue has demonstrated the infiltration of several immune cells such as
      macrophages, but dynamics of immune cells have not been fully elucidated and
      clarified. Here, by using intravital multiphoton imaging technique, to our
      knowledge for the first time, we analyzed and visualized the inflammatory
      processes in adipose tissue under high-fat and high-sucrose (HF/HS) diet with
      lysozyme M-EGFP transgenic (LysM(EGFP)) mice whose EGFP was specifically
      expressed in the myelomonocytic lineage. Mobility of LysM(EGFP)-positive
      macrophages was shown to be activated just 5 d after HF/HS diet, when the
      distinct hypertrophy of adipocytes and the accumulation of macrophages still have
      not become prominent. Significant increase of S100A8 was detected in mature
      adipocyte fraction just 5 d after HF/HS diet. Recombinant S100A8 protein
      stimulated chemotactic migration in vitro and in vivo, as well as induced
      proinflammatory molecules, both macrophages and adipocytes, such as TNF-alpha and
      chemokine (C-C motif) ligand 2. Finally, an antibody against S100A8 efficiently
      suppressed the HF/HS diet-induced initial inflammatory change, i.e., increased
      mobilization of adipose LysM(EGFP)-positive macrophages, and ameliorated HF/HS
      diet-induced insulin resistance. In conclusion, time-lapse intravital multiphoton
      imaging of adipose tissues identified the very early event exhibiting increased
      mobility of macrophages, which may be triggered by increased expression of
      adipose S100A8 and results in progression of chronic inflammation in situ. 

PMID- 25848058
TI  - Shapely DNA attracts the right partner.

PMID- 25848060
TI  - The human prenatal sex ratio: A major surprise.

PMID- 25848059
TI  - Potential role for snoRNAs in PKR activation during metabolic stress.
AB  - Protein kinase RNA-activated (PKR) has long been known to be activated by viral
      double-stranded RNA (dsRNA) as part of the mammalian immune response. However, in
      mice PKR is also activated by metabolic stress in the absence of viral infection,
      and this requires a functional kinase domain, as well as a functional dsRNA
      binding domain. The endogenous cellular RNA that potentially leads to PKR
      activation during metabolic stress is unknown. We investigated this question
      using mouse embryonic fibroblast cells expressing wild-type PKR (PKRWT) or PKR
      with a point mutation in each dsRNA-binding motif (PKRRM). Using this system, we
      identified endogenous RNA that interacts with PKR after induction of metabolic
      stress by palmitic acid (PA) treatment. Specifically, RIP-Seq analyses showed
      that the majority of enriched RNAs that interacted with WT PKR (>=twofold, false
      discovery rate <= 5%) were small nucleolar RNAs (snoRNAs). Immunoprecipitation of
      PKR in extracts of UV-cross-linked cells, followed by RT-qPCR, confirmed that
      snoRNAs were enriched in PKRWT samples after PA treatment, but not in the PKRRM
      samples. We also demonstrated that a subset of identified snoRNAs bind and
      activate PKR in vitro; the presence of a 5'-triphosphate enhanced PKR activity
      compared with the activity with a 5'-monophosphate, for some, but not all,
      snoRNAs. Finally, we demonstrated PKR activation in cells upon snoRNA
      transfection, supporting our hypothesis that endogenous snoRNAs can activate PKR.
      Our results suggest an unprecedented and unexpected model whereby snoRNAs play a
      role in the activation of PKR under metabolic stress. 

PMID- 25848061
TI  - Female peers in small work groups enhance women's motivation, verbal
      participation, and career aspirations in engineering.
AB  - For years, public discourse in science education, technology, and policy-making
      has focused on the "leaky pipeline" problem: the observation that fewer women
      than men enter science, technology, engineering, and mathematics fields and more
      women than men leave. Less attention has focused on experimentally testing
      solutions to this problem. We report an experiment investigating one solution: we
      created "microenvironments" (small groups) in engineering with varying
      proportions of women to identify which environment increases motivation and
      participation, and whether outcomes depend on students' academic stage. Female
      engineering students were randomly assigned to one of three engineering groups of
      varying sex composition: 75% women, 50% women, or 25% women. For first-years,
      group composition had a large effect: women in female-majority and sex-parity
      groups felt less anxious than women in female-minority groups. However, among
      advanced students, sex composition had no effect on anxiety. Importantly, group
      composition significantly affected verbal participation, regardless of women's
      academic seniority: women participated more in female-majority groups than sex
      parity or female-minority groups. Additionally, when assigned to female-minority
      groups, women who harbored implicit masculine stereotypes about engineering
      reported less confidence and engineering career aspirations. However, in sex
      parity and female-majority groups, confidence and career aspirations remained
      high regardless of implicit stereotypes. These data suggest that creating small
      groups with high proportions of women in otherwise male-dominated fields is one
      way to keep women engaged and aspiring toward engineering careers. Although sex
      parity works sometimes, it is insufficient to boost women's verbal participation
      in group work, which often affects learning and mastery. 

PMID- 25848062
TI  - Probing liquid dynamics, one molecule at a time.

PMID- 25848063
TI  - Smaller human population in 2100 could importantly reduce the risk of climate
      catastrophe.

PMID- 25848064
TI  - Reply to Wilkinson: Minor role of programmed methylation and demethylation in
      mammalian development.

PMID- 25848065
TI  - Evidence that DNA methylation engenders dynamic gene regulation.

PMID- 25848066
TI  - Reply to van de Sandt and Rimmelzwaan: Matching epitope display with functional
      avidity.

PMID- 25848067
TI  - Immunodominant responses to the influenza virus M158-66 epitope: Stealth or
      protection?

PMID- 25848068
TI  - Comment on "cutting edge: epigenetic regulation of Foxp3 defines a stable
      population of CD4+ regulatory T cells in tumors from mice and humans".

PMID- 25848069
TI  - Response to comment on "cutting edge: epigenetic regulation of Foxp3 defines a
      stable population of CD4+ regulatory T cells in tumors from mice and humans".

PMID- 25848070
TI  - Endothelial actin-binding proteins and actin dynamics in leukocyte
      transendothelial migration.
AB  - The endothelium is the first barrier that leukocytes have to overcome during
      recruitment to sites of inflamed tissues. The leukocyte extravasation cascade is
      a complex multistep process that requires the activation of various adhesion
      molecules and signaling pathways, as well as actin remodeling, in both leukocytes
      and endothelial cells. Endothelial adhesion molecules, such as E-selectin or ICAM
      1, are connected to the actin cytoskeleton via actin-binding proteins (ABPs).
      Although the contribution of receptor-ligand interactions to leukocyte
      extravasation has been studied extensively, the contribution of endothelial ABPs
      to the regulation of leukocyte adhesion and transendothelial migration remains
      poorly understood. This review focuses on recently published evidence that
      endothelial ABPs, such as cortactin, myosin, or alpha-actinin, regulate leukocyte
      extravasation by controlling actin dynamics, biomechanical properties of
      endothelia, and signaling pathways, such as GTPase activation, during
      inflammation. Thus, ABPs may serve as targets for novel treatment strategies for
      disorders characterized by excessive leukocyte recruitment. 

PMID- 25848071
TI  - Is the complement activation product C3a a proinflammatory molecule? Re
      evaluating the evidence and the myth.
AB  - The complement activation product C3a is often described as a proinflammatory
      mediator, alongside its downstream cousin, C5a. However, emerging studies show
      that C3a has several anti-inflammatory facets in vivo. For example, in the acute
      inflammatory response, C3a acts in direct opposition to C5a, through preventing
      the accumulation of neutrophils in inflamed tissues by independently regulating
      their mobilization. This acute, protective, and opposing activity of C3a to C5a
      is also illustrated in models of septicemia. In this article, we reinvestigate
      the discovery and original classification of C3a as a proinflammatory mediator
      and highlight the emerging studies demonstrating anti-inflammatory effects for
      C3a in the immune response. It is our hope that this review illuminates these
      apparently contradictory roles for C3a and challenges the general dogma
      surrounding C3a, which, historically, has ubiquitously been described as a
      proinflammatory mediator. In light of this, we urge investigators to use
      "inflammatory modulator" as the descriptor for C3a. 

PMID- 25848072
TI  - Comparative effectiveness of autologous blood-derived products, shock-wave
      therapy and corticosteroids for treatment of plantar fasciitis: a network meta
      analysis.
AB  - OBJECTIVE: To compare the efficacy of autologous blood-derived products (ABPs),
      CSs and shock-wave (SW) therapy in the treatment of plantar fasciitis. METHODS:
      Electronic databases were searched for studies that compared ABPs, CSs and SW
      therapy for the treatment of plantar fasciitis, published up to June 2014. The
      primary and secondary outcomes were reduction in visual analogue scale (VAS)
      score at 3 and 6 months and odds ratio of treatment success, respectively. Groups
      were compared by traditional pair-wise meta-analysis and by network meta
      analysis. RESULTS: Seven randomized controlled trials and three quasi
      experimental studies that included 604 patients were enrolled. Pair-wise meta
      analysis indicated a trend favouring ABPs over CSs regarding VAS reduction at 3
      months; this benefit was significant in a subgroup analysis of platelet-rich
      plasma (PRP) vs CSs. There were no significant between-group differences in VAS
      reduction at 6 months and in treatment success. Network meta-analysis showed that
      ABPs had the highest probability of being the best treatment at 3 months, but
      ABPs were slightly inferior to SW for VAS reduction at 6 months. Although SW
      therapy had the highest likelihood of treatment success, the between-group
      differences in probabilities were less remarkable than those for pain reduction
      at 3 and 6 months. CONCLUSION: ABPs, followed by CSs, were best in providing
      relief from pain at 3 months. SW therapy and ABPs had similar probabilities of
      providing pain relief at 6 months, and were better than CSs at that time.
      Subgroup analysis indicated that an ABP regimen consisting of platelet-rich
      plasma improves treatment efficacy.

PMID- 25848073
TI  - Caveolin-1 Deficiency Inhibits the Basolateral K+ Channels in the Distal
      Convoluted Tubule and Impairs Renal K+ and Mg2+ Transport.
AB  - Kcnj10 encodes the inwardly rectifying K(+) channel Kir4.1 in the basolateral
      membrane of the distal convoluted tubule (DCT) and is activated by c-Src.
      However, the regulation and function of this K(+) channel are incompletely
      characterized. Here, patch-clamp experiments in Kcnj10-transfected HEK293 cells
      demonstrated that c-Src-induced stimulation of Kcnj10 requires coexpression of
      caveolin-1 (cav-1), and immunostaining showed expression of cav-1 in the
      basolateral membrane of parvalbumin-positive DCT. Patch-clamp experiments
      detected a 40-pS inwardly rectifying K(+) channel, a heterotetramer of
      Kir4.1/Kir5.1, in the basolateral membrane of the early DCT (DCT1) in both wild
      type (WT) and cav-1-knockout (KO) mice. However, the activity of this basolateral
      40-pS K(+) channel was lower in KO mice than in WT mice. Moreover, the K(+)
      reversal potential (an indication of membrane potential) was less negative in the
      DCT1 of KO mice than in the DCT1 of WT mice. Western blot analysis demonstrated
      that cav-1 deficiency decreased the expression of the Na(+)/Cl(-) cotransporter
      and Ste20-proline-alanine-rich kinase (SPAK) but increased the expression of
      epithelial Na(+) channel-alpha. Furthermore, the urinary excretion of Mg(2+) and
      K(+) was significantly higher in KO mice than in WT mice, and KO mice developed
      hypomagnesemia, hypocalcemia, and hypokalemia. We conclude that disruption of cav
      1 decreases basolateral K(+) channel activity and depolarizes the cell membrane
      potential in the DCT1 at least in part by suppressing the stimulatory effect of c
      Src on Kcnj10. Furthermore, the decrease in Kcnj10 and Na(+)/Cl(-) cotransporter
      expression induced by cav-1 deficiency may underlie the compromised renal
      transport of Mg(2+), Ca(2+), and K(+). 

PMID- 25848074
TI  - Romantic partner influences on prenatal and postnatal substance use in young
      couples.
AB  - BACKGROUND: Alcohol, tobacco and other drug use (ATOD) among adolescent and young
      adult couples during prenatal and postnatal periods is a significant public
      health problem, and couples may mutually influence each others' ATOD behaviors.
      PURPOSE: The current study investigated romantic partner influences on ATOD among
      adolescent and young adult couples during pregnancy and postnatal periods.
      METHODS: Participants were 296 young couples in the second or third trimester of
      pregnancy recruited from OBGYN clinics between July 2007 and February 2011.
      Participants completed questionnaires at prenatal, 6 months postnatal, and 12
      months postnatal periods. Dyadic data analysis was conducted to assess the
      stability and interdependence of male and female ATOD over time. RESULTS: Male
      partner cigarette and marijuana use in the prenatal period significantly
      predicted female cigarette and marijuana use at 6 months postnatal (b = 0.14, P <
      0.01; b = 0.11, P < 0.05, respectively). Male partner marijuana use at 6 months
      postnatal also significantly predicted female marijuana use at 12 months
      postnatal (b = 0.11, P < 0.05). Additionally, significant positive correlations
      were found for partner alcohol and marijuana at pre-pregnancy and 6 months
      postnatal, and partner cigarette use at pre-pregnancy, 6 months and 12 months
      postnatal. CONCLUSIONS: Partner ATOD among young fathers, particularly during the
      prenatal period, may play an important role in subsequent ATOD among young
      mothers during postnatal periods.

PMID- 25848075
TI  - A dynamical model of plasma turbulence in the solar wind.
AB  - A dynamical approach, rather than the usual statistical approach, is taken to
      explore the physical mechanisms underlying the nonlinear transfer of energy, the
      damping of the turbulent fluctuations, and the development of coherent structures
      in kinetic plasma turbulence. It is argued that the linear and nonlinear dynamics
      of Alfven waves are responsible, at a very fundamental level, for some of the key
      qualitative features of plasma turbulence that distinguish it from hydrodynamic
      turbulence, including the anisotropic cascade of energy and the development of
      current sheets at small scales. The first dynamical model of kinetic turbulence
      in the weakly collisional solar wind plasma that combines self-consistently the
      physics of Alfven waves with the development of small-scale current sheets is
      presented and its physical implications are discussed. This model leads to a
      simplified perspective on the nature of turbulence in a weakly collisional
      plasma: the nonlinear interactions responsible for the turbulent cascade of
      energy and the formation of current sheets are essentially fluid in nature, while
      the collisionless damping of the turbulent fluctuations and the energy injection
      by kinetic instabilities are essentially kinetic in nature. 

PMID- 25848076
TI  - Turbulent reconnection and its implications.
AB  - Magnetic reconnection is a process of magnetic field topology change, which is
      one of the most fundamental processes happening in magnetized plasmas. In most
      astrophysical environments, the Reynolds numbers corresponding to plasma flows
      are large and therefore the transition to turbulence is inevitable. This
      turbulence, which can be pre-existing or driven by magnetic reconnection itself,
      must be taken into account for any theory of magnetic reconnection that attempts
      to describe the process in the aforementioned environments. This necessity is
      obvious as three-dimensional high-resolution numerical simulations show the
      transition to the turbulence state of initially laminar reconnecting magnetic
      fields. We discuss ideas of how turbulence can modify reconnection with the focus
      on the Lazarian & Vishniac (Lazarian & Vishniac 1999 Astrophys. J. 517, 700-718
      (doi:10.1086/307233)) reconnection model. We present numerical evidence
      supporting the model and demonstrate that it is closely connected to the
      experimentally proven concept of Richardson dispersion/diffusion as well as to
      more recent advances in understanding of the Lagrangian dynamics of magnetized
      fluids. We point out that the generalized Ohm's law that accounts for turbulent
      motion predicts the subdominance of the microphysical plasma effects for
      reconnection for realistically turbulent media. We show that one of the most
      dramatic consequences of turbulence is the violation of the generally accepted
      notion of magnetic flux freezing. This notion is a cornerstone of most theories
      dealing with magnetized plasmas, and therefore its change induces fundamental
      shifts in accepted paradigms, for instance, turbulent reconnection entails
      reconnection diffusion process that is essential for understanding star
      formation. We argue that at sufficiently high Reynolds numbers the process of
      tearing reconnection should transfer to turbulent reconnection. We discuss flares
      that are predicted by turbulent reconnection and relate this process to solar
      flares and gamma-ray bursts. With reference to experiments, we analyse solar
      observations in situ as measurements in the solar wind or heliospheric current
      sheet and show the correspondence of data with turbulent reconnection
      predictions. Finally, we discuss first-order Fermi acceleration of particles that
      is a natural consequence of the turbulent reconnection.

PMID- 25848077
TI  - Dissipation and heating in solar wind turbulence: from the macro to the micro and
      back again.
AB  - The past decade has seen a flurry of research activity focused on discerning the
      physics of kinetic scale turbulence in high-speed astrophysical plasma flows. By
      'kinetic' we mean spatial scales on the order of or, in particular, smaller than
      the ion inertial length or the ion gyro-radius--the spatial scales at which the
      ion and electron bulk velocities decouple and considerable change can be seen in
      the ion distribution functions. The motivation behind most of these studies is to
      find the ultimate fate of the energy cascade of plasma turbulence, and thereby
      the channels by which the energy in the system is dissipated. This brief
      Introduction motivates the case for a themed issue on this topic and introduces
      the topic of turbulent dissipation and heating in the solar wind. The theme issue
      covers the full breadth of studies: from theory and models, massive simulations
      of these models and observational studies from the highly rich and vast amount of
      data collected from scores of heliospheric space missions since the dawn of the
      space age. A synopsis of the theme issue is provided, where a brief description
      of all the contributions is discussed and how they fit together to provide an
      over-arching picture on the highly topical subject of dissipation and heating in
      turbulent collisionless plasmas in general and in the solar wind in particular.

PMID- 25848078
TI  - Dynamic properties of small-scale solar wind plasma fluctuations.
AB  - The paper presents the latest results of the studies of small-scale fluctuations
      in a turbulent flow of solar wind (SW) using measurements with extremely high
      temporal resolution (up to 0.03 s) of the bright monitor of SW (BMSW) plasma
      spectrometer operating on astrophysical SPECTR-R spacecraft at distances up to
      350,000 km from the Earth. The spectra of SW ion flux fluctuations in the range
      of scales between 0.03 and 100 s are systematically analysed. The difference of
      slopes in low- and high-frequency parts of spectra and the frequency of the break
      point between these two characteristic slopes was analysed for different
      conditions in the SW. The statistical properties of the SW ion flux fluctuations
      were thoroughly analysed on scales less than 10 s. A high level of intermittency
      is demonstrated. The extended self-similarity of SW ion flux turbulent flow is
      constantly observed. The approximation of non-Gaussian probability distribution
      function of ion flux fluctuations by the Tsallis statistics shows the non
      extensive character of SW fluctuations. Statistical characteristics of ion flux
      fluctuations are compared with the predictions of a log-Poisson model. The log
      Poisson parametrization of the structure function scaling has shown that well
      defined filament-like plasma structures are, as a rule, observed in the turbulent
      SW flows.

PMID- 25848079
TI  - Third-moment descriptions of the interplanetary turbulent cascade, intermittency
      and back transfer.
AB  - We review some aspects of solar wind turbulence with an emphasis on the ability
      of the turbulence to account for the observed heating of the solar wind.
      Particular attention is paid to the use of structure functions in computing
      energy cascade rates and their general agreement with the measured thermal proton
      heating. We then examine the use of 1 h data samples that are comparable in
      length to the correlation length for the fluctuations to obtain insights into
      local inertial range dynamics and find evidence for intermittency in the computed
      energy cascade rates. When the magnetic energy dominates the kinetic energy,
      there is evidence of anti-correlation in the cascade of energy associated with
      the outward- and inward-propagating components that we can only partially
      explain. 

PMID- 25848080
TI  - Generation of magnetic holes in fully kinetic simulations of collisionless
      turbulence.
AB  - The results of three-dimensional fully kinetic simulations of decaying turbulence
      with the amplitude of the fluctuating magnetic field comparable to that of the
      mean field are presented. Coherent structures in the form of localized
      depressions in the magnitude of the magnetic field are observed to form self
      consistently in the simulations. These depressions bear considerable resemblance
      to the so-called magnetic holes frequently reported in spacecraft observations.
      The structures are pressure-balanced and tend to be aligned with the local
      magnetic field. In the smallest structures observed, the decrease in the magnetic
      field strength is compensated by an increase in the electron perpendicular
      pressure, such that the transverse size of these structures is comparable to the
      electron gyroradius inside the depression. It is suggested that the structures
      evolve self-consistently out of the depressions in the fluctuating magnetic
      field, rather than being the consequence of instability growth and saturation.
      This is confirmed by additional, small-scale simulations, including those with
      realistic mass ratio between protons and electrons. 

PMID- 25848081
TI  - Short-wavelength plasma turbulence and temperature anisotropy instabilities:
      recent computational progress.
AB  - Plasma turbulence consists of an ensemble of enhanced, broadband electromagnetic
      fluctuations, typically driven by multi-wave interactions which transfer energy
      in wavevector space via non- linear cascade processes. Temperature anisotropy
      instabilities in collisionless plasmas are driven by quasi-linear wave-particle
      interactions which transfer particle kinetic energy to field fluctuation energy;
      the resulting enhanced fluctuations are typically narrowband in wavevector
      magnitude and direction. Whatever their sources, short-wavelength fluctuations
      are those at which charged particle kinetic, that is, velocity-space, properties
      are important; these are generally wavelengths of the order of or shorter than
      the ion inertial length or the thermal ion gyroradius. The purpose of this review
      is to summarize and interpret recent computational results concerning short
      wavelength plasma turbulence, short-wavelength temperature anisotropy
      instabilities and relationships between the two phenomena. 

PMID- 25848082
TI  - Anisotropy in solar wind plasma turbulence.
AB  - A review of spectral anisotropy and variance anisotropy for solar wind
      fluctuations is given, with the discussion covering inertial range and
      dissipation range scales. For the inertial range, theory, simulations and
      observations are more or less in accord, in that fluctuation energy is found to
      be primarily in modes with quasi-perpendicular wavevectors (relative to a
      suitably defined mean magnetic field), and also that most of the fluctuation
      energy is in the vector components transverse to the mean field. Energy transfer
      in the parallel direction and the energy levels in the parallel components are
      both relatively weak. In the dissipation range, observations indicate that
      variance anisotropy tends to decrease towards isotropic levels as the electron
      gyroradius is approached; spectral anisotropy results are mixed. Evidence for and
      against wave interpretations and turbulence interpretations of these features
      will be discussed. We also present new simulation results concerning evolution of
      variance anisotropy for different classes of initial conditions, each with
      typical background solar wind parameters. 

PMID- 25848083
TI  - The role of turbulence in coronal heating and solar wind expansion.
AB  - Plasma in the Sun's hot corona expands into the heliosphere as a supersonic and
      highly magnetized solar wind. This paper provides an overview of our current
      understanding of how the corona is heated and how the solar wind is accelerated.
      Recent models of magnetohydrodynamic turbulence have progressed to the point of
      successfully predicting many observed properties of this complex, multi-scale
      system. However, it is not clear whether the heating in open-field regions comes
      mainly from the dissipation of turbulent fluctuations that are launched from the
      solar surface, or whether the chaotic 'magnetic carpet' in the low corona
      energizes the system via magnetic reconnection. To help pin down the physics, we
      also review some key observational results from ultraviolet spectroscopy of the
      collisionless outer corona. 

PMID- 25848084
TI  - Kinetic scale turbulence and dissipation in the solar wind: key observational
      results and future outlook.
AB  - Turbulence is ubiquitous in the solar wind. Turbulence causes kinetic and
      magnetic energy to cascade to small scales where they are eventually dissipated,
      adding heat to the plasma. The details of how this occurs are not well
      understood. This article reviews the evidence for turbulent dissipation and
      examines various diagnostics for identifying solar wind regions where dissipation
      is occurring. We also discuss how future missions will further enhance our
      understanding of the importance of turbulence to solar wind dynamics. 

PMID- 25848085
TI  - Intermittency, nonlinear dynamics and dissipation in the solar wind and
      astrophysical plasmas.
AB  - An overview is given of important properties of spatial and temporal
      intermittency, including evidence of its appearance in fluids, magnetofluids and
      plasmas, and its implications for understanding of heliospheric plasmas. Spatial
      intermittency is generally associated with formation of sharp gradients and
      coherent structures. The basic physics of structure generation is ideal, but when
      dissipation is present it is usually concentrated in regions of strong gradients.
      This essential feature of spatial intermittency in fluids has been shown recently
      to carry over to the realm of kinetic plasma, where the dissipation function is
      not known from first principles. Spatial structures produced in intermittent
      plasma influence dissipation, heating, and transport and acceleration of charged
      particles. Temporal intermittency can give rise to very long time correlations or
      a delayed approach to steady-state conditions, and has been associated with
      inverse cascade or quasi-inverse cascade systems, with possible implications for
      heliospheric prediction. 

PMID- 25848086
TI  - A stuck haemodialysis central venous catheter: not quite open and shut!
AB  - Removal of tunnelled central venous catheters can become complex if left in situ
      for a prolonged period. We report a challenging case of a stuck tunnelled
      haemodialysis catheter, which required sternotomy with cardio-pulmonary bypass
      for retrieval. A 47-year-old female had failed attempts to remove the venous limb
      of a Tessio line on the ward. A cut down on the internal jugular vein and
      division of the fibrin sheath failed to release it. Synchronous traction was
      applied via a snare inserted through a femoral approach. On table trans
      oesophageal echocardiogram showed the tip of the catheter traversing the
      tricuspid valve. At sternotomy with cardio-pulmonary bypass, the tip of the
      catheter was found attached to the septal leaflet of the tricuspid valve
      requiring release and repair. The management of stuck line has potential serious
      complications. Prophylactic catheter exchange should be considered to avoid
      complications. 

PMID- 25848087
TI  - Solid pseudopapillary tumor of the pancreas in a patient with cervical cancer:
      relation of E-cadherin/beta-catenin adhesion complex in their carcinogenesis.
AB  - Solid pseudopapillary tumor (SPT) of the pancreas is one of the most uncommon
      histotypes of all exocrine pancreatic neoplasms. Disorganization of E-cadherin
      and beta-catenin mutations, two key components of the Wnt signal transduction
      pathway, has been implicated in the development of SPT, but not other pancreatic
      tumors. Loss of E-cadherin/beta-catenin proteins and tyrosine phosphorylation of
      E-cadherin/beta-catenin have been postulated in cervical carcinogenesis and
      cancer invasion. A 38-year-old married woman, who had undergone brachytherapy,
      radiotherapy and chemotherapy for cervical cancer in Philippines in 2011, was
      admitted to our hospital after follow-up CT scan of abdomen in 2012 revealed a
      lesion in the tail of pancreas. The patient underwent distal pancreatectomy and
      splenectomy. The pathological diagnosis was SPT of pancreas. We suspect that the
      concurrent SPT pancreas and cervical cancer in this woman were triggered by a
      primary insult, a process in which E-cadherin/beta-catenin/Wnt-signaling pathway
      played important roles. 

PMID- 25848088
TI  - Giant sialolith of submandibular gland: report of a case?.
AB  - Sialolithiasis is one of the most common diseases of salivary glands in middle
      aged patients. Sialoliths are localized in submandibular glands in nearly 80% of
      the reported cases and they are classified as 'giant' in case any dimension
      exceeds 15 mm. Giant sialolith in submandibular gland is a rare disorder. Here,
      an unusual case of giant sialolith in submandibular gland is reported. A 42-year
      old man referred with complaints of recurrent pain and swelling in the left
      submandibular area. Computerized tomography revealed a calcified mass of 42 * 17
      mm size within the submandibular gland. Excision was performed in the
      submandibular gland and a giant sialolith of 35 mm length localized in the body
      of the gland was detected. The postoperative period was uneventful and the
      patient fully recovered. 

PMID- 25848089
TI  - Quality Control Pathways for Nucleus-Encoded Eukaryotic tRNA Biosynthesis and
      Subcellular Trafficking.
AB  - tRNAs perform an essential role in translating the genetic code. They are long
      lived RNAs that are generated via numerous posttranscriptional steps. Eukaryotic
      cells have evolved numerous layers of quality control mechanisms to ensure that
      the tRNAs are appropriately structured, processed, and modified. We describe the
      known tRNA quality control processes that check tRNAs and correct or destroy
      aberrant tRNAs. These mechanisms employ two types of exonucleases, CCA end
      addition, tRNA nuclear aminoacylation, and tRNA subcellular traffic. We arrange
      these processes in order of the steps that occur from generation of precursor
      tRNAs by RNA polymerase (Pol) III transcription to end maturation and
      modification in the nucleus to splicing and additional modifications in the
      cytoplasm. Finally, we discuss the tRNA retrograde pathway, which allows tRNA
      reimport into the nucleus for degradation or repair. 

PMID- 25848090
TI  - Histone methyltransferase Setd8 represses Gata2 expression and regulates
      erythroid maturation.
AB  - Setd8 is the sole histone methyltransferase in mammals capable of monomethylating
      histone H4 lysine 20 (H4K20me1). Setd8 is expressed at significantly higher
      levels in erythroid cells than any other cell or tissue type, suggesting that
      Setd8 has an erythroid-cell-specific function. To test this hypothesis, stable
      Setd8 knockdown was established in extensively self-renewing erythroblasts
      (ESREs), a well-characterized, nontransformed model of erythroid maturation.
      Knockdown of Setd8 resulted in impaired erythroid maturation characterized by a
      delay in hemoglobin accumulation, larger mean cell area, persistent ckit
      expression, incomplete nuclear condensation, and lower rates of enucleation.
      Setd8 knockdown did not alter ESRE proliferation or viability or result in
      accumulation of DNA damage. Global gene expression analyses following Setd8
      knockdown demonstrated that in erythroid cells, Setd8 functions primarily as a
      repressor. Most notably, Gata2 expression was significantly higher in knockdown
      cells than in control cells and Gata2 knockdown rescued some of the maturation
      impairments associated with Setd8 disruption. Setd8 occupies critical regulatory
      elements in the Gata2 locus, and knockdown of Setd8 resulted in loss of H4K20me1
      and gain of H4 acetylation at the Gata2 1S promoter. These results suggest that
      Setd8 is an important regulator of erythroid maturation that works in part
      through repression of Gata2 expression. 

PMID- 25848091
TI  - Role for Protein Kinase A in the Neurospora Circadian Clock by Regulating White
      Collar-Independent frequency Transcription through Phosphorylation of RCM-1.
AB  - Rhythmic activation and repression of clock gene expression is essential for the
      eukaryotic circadian clock functions. In the Neurospora circadian oscillator, the
      transcription of the frequency (frq) gene is periodically activated by the White
      Collar (WC) complex and suppressed by the FRQ-FRH complex. We previously showed
      that there is WC-independent frq transcription and its repression is required for
      circadian gene expression. How WC-independent frq transcription is regulated is
      not known. We show here that elevated protein kinase A (PKA) activity results in
      WC-independent frq transcription and the loss of clock function. We identified
      RCM-1 as the protein partner of RCO-1 and an essential component of the clock
      through its role in suppressing WC-independent frq transcription. RCM-1 is a
      phosphoprotein and is a substrate of PKA in vivo and in vitro. Mutation of the
      PKA-dependent phosphorylation sites on RCM-1 results in WC-independent
      transcription of frq and impaired clock function. Furthermore, we showed that RCM
      1 is associated with the chromatin at the frq locus, a process that is inhibited
      by PKA. Together, our results demonstrate that PKA regulates frq transcription by
      inhibiting RCM-1 activity through RCM-1 phosphorylation. 

PMID- 25848094
TI  - Estimation of organ doses and effective doses in image-guided respiration-gated
      radiotherapy.
AB  - Dose conformity in thoracic and abdominal ion-beam radiotherapy is degraded by
      respiratory motion. To improve conformity, an image-guided respiration-gated
      system can be used in the treatment room. The purpose of this study was to
      estimate the organ doses and effective doses to patients from an image-guided
      respiration-gated system. Glass dosemeters were inserted into an adult
      anthropomorphic phantom and were attached to the surface on the phantom. The
      phantom was placed on the treatment couch, and the imaging dose from fluoroscopy
      was evaluated. In addition to the organ doses, the effective doses were also
      estimated according to the ICRP Publication 103. The irradiation time is over 3-5
      min per beam angle. When image acquisition conditions were assumed for thoracic
      treatment, the effective doses and maximal skin doses were 0.48-0.79 mSv and 5.9
      9.9 mGy, respectively. The estimated doses can be the base data for considering
      radiological protection in the radiotherapy. 

PMID- 25848093
TI  - Structural Basis for Pharmacology of Voltage-Gated Sodium and Calcium Channels.
AB  - Voltage-gated sodium channels initiate action potentials in nerve, muscle, and
      other electrically excitable cells. Voltage-gated calcium channels are activated
      by depolarization during action potentials, and calcium influx through them is
      the key second messenger of electrical signaling, initiating secretion,
      contraction, neurotransmission, gene transcription, and many other intracellular
      processes. Drugs that block sodium channels are used in local anesthesia and the
      treatment of epilepsy, bipolar disorder, chronic pain, and cardiac arrhythmia.
      Drugs that block calcium channels are used in the treatment of epilepsy, chronic
      pain, and cardiovascular disorders, including hypertension, angina pectoris, and
      cardiac arrhythmia. The principal pore-forming subunits of voltage-gated sodium
      and calcium channels are structurally related and likely to have evolved from
      ancestral voltage-gated sodium channels that are widely expressed in prokaryotes.
      Determination of the structure of a bacterial ancestor of voltage-gated sodium
      and calcium channels at high resolution now provides a three-dimensional view of
      the binding sites for drugs acting on sodium and calcium channels. In this
      minireview, we outline the different classes of sodium and calcium channel drugs,
      review studies that have identified amino acid residues that are required for
      their binding and therapeutic actions, and illustrate how the analogs of those
      key amino acid residues may form drug-binding sites in three-dimensional models
      derived from bacterial channels. 

PMID- 25848095
TI  - Paediatric doses in St Petersburg hospitals.
AB  - The exposure of paediatric patients during X-ray examinations in St Petersburg
      hospitals was investigated. Data about radiography examinations were collected,
      and mean patient effective doses and entrance surface air kerma for each X-ray
      unit were estimated. The results of the study were compared with other countries
      practice. This data will be used to optimise paediatric conventional X-ray
      examinations in Russia. 

PMID- 25848096
TI  - Reduction of occupational radiation dose in staff at the cardiac catheterisation
      laboratory by protective material placed on the patient.
AB  - Reducing occupational radiation dose in cardiac catheterisation laboratories is
      one of the objectives of the radiation protection system because the procedures
      performed involve high levels of radiation compared with others in health care.
      Recommendations on protection methods used are referred to different structural
      types and personal protection tools. In this work, the effectiveness of a
      shielding drape above the patient in different geometric shapes for a standard
      procedure in interventional cardiology was evaluated. Values of personal dose
      equivalent Hp(10) obtained simultaneously with three active electronic
      semiconductor dosemeters located at the usual position of staff and at the C-arm
      have been used to show the usefulness of the shielding drape. 

PMID- 25848097
TI  - Reaction mechanism interplay in determining the biological effectiveness of
      neutrons as a function of energy.
AB  - Neutron relative biological effectiveness (RBE) is found to be energy dependent,
      being maximal for energies ~1 MeV. This is reflected in the choice of radiation
      weighting factors wR for radiation protection purposes. In order to trace back
      the physical origin of this behaviour, a detailed study of energy deposition
      processes with their full dependences is necessary. In this work, the Monte Carlo
      transport code PHITS was used to characterise main secondary products responsible
      for energy deposition in a 'human-sized' soft tissue spherical phantom,
      irradiated by monoenergetic neutrons with energies around the maximal RBE/wR.
      Thereafter, results on the microdosimetric characterisation of secondary protons
      were used as an input to track structure calculations performed with PARTRAC,
      thus evaluating the corresponding DNA damage induction. Within the proposed
      simplified approach, evidence is suggested for a relevant role of secondary
      protons in inducing the maximal biological effectiveness for 1 MeV neutrons.

PMID- 25848098
TI  - Nanodosimetric descriptors of the radiation quality of carbon ions.
AB  - In view of the emerging interest of carbon ions in radiotherapy and of the strong
      correlation between the track structure and the radiobiological effectiveness of
      ionising radiations, the track-structure properties of (12)C-ions were studied at
      particle energies close to the Bragg peak. To perform the investigations,
      ionisation-cluster-size distributions for nanometre-sized target volumes were
      measured with the track-nanodosimeter installed at the TANDEM-ALPI accelerator
      complex at LNL, and calculated using a dedicated Monte Carlo simulation code. The
      resulting cluster-size distributions are used to derive particular descriptors of
      particle track structure. Here, the main emphasis is laid on the mean ionisation
      cluster size M1 and the cumulative probability Fk of measuring cluster sizes nu
      >= k. From the radiobiological point of view, Fk is of particular interest
      because an increasing k corresponds to an increase of damages of higher
      complexity. In addition, Fk saturates with increasing radiation quality like
      radiobiological cross sections as a function of linear energy transfer. Results
      will be presented and discussed for (12)C-ions at 96 and 240 MeV. 

PMID- 25848099
TI  - Radiation protection aspects of EMITEL Encyclopaedia of Medical Physics.
AB  - The Encyclopaedia of Medical Physics EMITEL was developed under the EU pilot
      project European Medical Imaging Technology e-Encyclopaedia for Lifelong
      Learning. This large reference material includes 3400 articles on 2100 pages
      supported by thousands of illustrations. All materials are available free at the
      website, www.emitel2.eu. The articles are grouped in seven categories--physics
      of: X-ray diagnostic radiology, nuclear medicine, radiotherapy, magnetic
      resonance imaging, ultrasound imaging, radiation protection and general terms.
      The radiation protection part of EMITEL includes 450 articles. These were
      organised in several sub-groups including: nuclear and atomic physics; ionizing
      radiation interactions and biological effects; radiation detection and
      measurement; dosimetric quantities and units; and general radiation protection
      and international bodies. EMITEL project was developed over 3 y and attracted as
      contributors 250+ senior specialists from 35 countries. After its successful
      launching, EMITEL is actively used by thousands of professionals around the
      world.

PMID- 25848100
TI  - Collective effective dose from diagnostic radiology in Ukraine.
AB  - The frequencies and effective doses for the most common X-ray diagnostic
      examinations in Ukraine were assessed in the frame of the European Commission
      (EC) Study on European Population Doses from Medical Exposure (Dose Datamed 2).
      The average effective doses for all radiographic procedures were estimated using
      the ODS-60 software (Finland). The estimation of the effective doses for the
      chest film fluorography was carried out from the results of own representative
      measurements with thermoluminescent (TL) dosimetry and a standard Alderson-Rando
      phantom. The effective doses for fluoroscopy procedures were assessed using the
      Russian guidelines for estimation of effective doses. For all other X-ray
      examinations and procedures [computed tomography (CT), angiography and
      interventional procedures], typical effective dose values were taken from the EC
      Guidance RP154. The most frequently performed in Ukraine is chest film
      fluorography, with 389 examinations per 1000 population annually, reflecting in
      the greatest contribution to the total collective effective dose (CED) of 428 mSv
      per 1000 population (44 %). The total frequency and CED from all X-ray diagnostic
      examinations and procedures were estimated to be 1218 examinations and 1060 mSv
      per 1000 populations, respectively. The expected additional cancer risk from X
      ray diagnostic examinations and interventional procedures is 2680 cases per year,
      with 1200 of them due to the contribution of chest fluorography. The main
      important action in radiation protection of patients in diagnostic radiology is
      the organisation of the monitoring of patient doses for different types of X-ray
      diagnostic examinations and replacement of chest film fluorography with digital X
      ray systems. 

PMID- 25848101
TI  - Mechanisms of the induction of apoptosis mediated by radiation-induced cytokine
      release.
AB  - The aim of the present work was to investigate the mechanisms of radiation
      induced bystander signalling leading to apoptosis in non-irradiated co-cultured
      cells. Cultured non-transformed cells were irradiated, and the effect on the
      apoptosis rate on co-cultured non-irradiated malignant cells was determined. For
      this, two different levels of the investigation are presented, i.e. release of
      signalling proteins and transcriptomic profiling of the irradiated and non
      irradiated co-cultured cells. Concerning the signalling proteins, in this study,
      the attention was focussed on the release of the active and latent forms of the
      transforming growth factor-beta1 protein. Moreover, global gene expression
      profiles of non-transformed and transformed cells in untreated co-cultures were
      compared with those of 0.5-Gy-irradiated non-transformed cells co-cultured with
      the transformed cells. The results show an effect of radiation on the release of
      signalling proteins in the medium, although no significant differences in release
      rates were detectable when varying the doses in the range from 0.25 to 1 Gy.
      Moreover, gene expression results suggest an effect of radiation on both cell
      populations, pointing out specific signalling pathways that might be involved in
      the enhanced induction of apoptosis. 

PMID- 25848102
TI  - Romanian medical exposure to ionising radiation in 2012.
AB  - Medical exposure, the main source of artificial exposure, shows an increasing
      trend in the last years, manifested both by increasing the number of examinations
      with ionising radiation and by increasing the patient dose level. Annual results
      obtained for medical exposure to ionising radiation based on the data collected
      from Romanian hospitals are useful for the update of the national database and
      optimisation of diagnostic procedures in radiology and nuclear medicine. Medical
      exposure level is expressed in terms of annual collective dose and is evaluated
      from annual frequencies and the average effective dose per procedure for
      different types of radiological and nuclear medicine procedures. The Romanian
      hospitals reported during 2012 a number of 5,505,792 radiological examinations
      and 17,088 diagnostic procedures of nuclear medicine. Based on the data reported,
      the average effective doses and their contributions to the collective dose were
      evaluated. The main contributions to the collective dose of the radiological
      procedures are registered for CT abdomen and pelvis region, followed by thorax CT
      and head CT examinations. The next positions are fluoroscopic examination of the
      thorax and gastrointestinal disease and radiographic examination of the lumbar
      spine and thorax, which in spite of their low effective dose have an important
      contribution to the collective dose due to the large number of examinations. For
      nuclear medicine procedures, major contributions to collective dose are given by
      bone scintigraphy, followed by PET-CT and thyroid scintigraphy.

PMID- 25848103
TI  - Evaluation of organ doses in adult and paediatric CT examinations based on Monte
      Carlo simulations and in-phantom dosimetry.
AB  - The aim of this study was to validate the computed tomography dose index (CTDI)
      and organ doses evaluated by Monte Carlo simulations through comparisons with
      doses evaluated by in-phantom dosimetry. Organ doses were measured with radio
      photoluminescence glass dosemeter (RGD) set at various organ positions within
      adult and 1-y-old anthropomorphic phantoms. For the dose simulations, the X-ray
      spectrum and bow-tie filter shape of a CT scanner were estimated and 3D voxelised
      data of the CTDI and anthropomorphic phantoms from the acquired CT images were
      derived. Organ dose simulations and measurements were performed with chest and
      abdomen-pelvis CT examination scan parameters. Relative differences between the
      simulated and measured doses were within 5 % for the volume CTDI and 13 % for
      organ doses for organs within the scan range in adult and paediatric CT
      examinations. The simulation results were considered to be in good agreement with
      the measured doses. 

PMID- 25848104
TI  - Staff eye doses in a large medical centre in Saudi Arabia: are they meeting the
      new ICRP recommendations?
AB  - A 5-y retrospective analysis of the cardiology staff eye doses was performed on
      34 staff from different categories (cardiologists, nurses and technologists) at
      King Faisal Specialist Hospital and Research Centre (KFSHRC) in Riyadh, Saudi
      Arabia. KFSHRC is a tertiary medical centre with 800-bed capacity having more
      than 5000 cardiac catheterisation procedures performed annually. The aim of the
      study is to derive staff doses to the lens of the eyes using the personal dose
      equivalent Hp(0.07) values from the annual TLD dose report for the years 2008
      2012 and determine the category of staff with high estimated eye doses. The study
      also aims to investigate the causes for high doses and recommend dose-reduction
      techniques. The dose to the lens of the eye was estimated by using the ratio
      Hp(0.07)slab/Hlens of 1.1 where Hp(0.07) values are the reported doses read from
      TLD badge worn at the collar level. The average annual eye dose of each category
      for the 5-y monitoring period was determined. Cardiologists tend to receive
      higher doses than the nurses by a factor of 2-4 and can exceed 5 mSv y(-1). No
      correlation exists between the eye doses of nurses and the cardiologists. There
      is a need to use a conversion coefficient in terms of eye lens dose per dose-area
      product for faster estimation of eye lens doses. However, there is a limitation
      on the use of the conversion coefficient because it will depend on the clinical
      procedure and the X-ray tube angulation. Further investigation on this limitation
      is needed. 

PMID- 25848105
TI  - Patient doses from PET-CT procedures.
AB  - Positron emission tomography (PET) was installed for the first time in Bulgaria
      in 2009, and nowadays two hybrid PET-computed tomography (CT) systems are in
      operation. The aim of this work is to estimate patient doses from PET-CT
      procedures and to explore potential for optimisation. Data were retrospectively
      collected for 50 patients examined with the system Philips Gemini TF and for 58
      patients examined with the system GE Discovery 600. Whole-body examinations with
      radiopharmaceutical (18)F-2-fluoro-2-deoxy-D-glucose (FDG) were performed on all
      patients. Patient effective doses from the CT component of the examination were
      calculated with CT Expo software and compared with doses estimated applying the
      National Radiological Protection Board (NRPB) conversion coefficients. Effective
      doses from the PET component were calculated applying the ICRP 80 conversion
      coefficients. For the first system, average effective doses from CT component
      were 8.0 and 8.9 mSv, applying CT Expo and NRPB coefficients, respectively, and
      4.9 mSv from PET component. For the second system, the corresponding values were
      7.8, 8.7 and 5.9 mSv. These results for patient effective doses are relatively
      lower or comparable to other similar surveys. Reasons for the observed
      differences are analysed and presented.

PMID- 25848106
TI  - Cutting down the radiation dose on CT urography: how it is done and what results
      are received?
AB  - Computed tomography urography (CTU) is a very detailed and powerful method of
      investigating the urinary tract, but an individual approach to each patient is
      recommended considering also the radiation dose. This article aims to present the
      initial experience from the diagnosis of urinary tract diseases and congenital
      variants in the anatomy of the urinary system using low-kV protocols. The image
      quality and patient dose in CTU were compared when replacing the standard 120-kV
      protocol with two different low-kV protocols. Totally, 91 patients (41 women and
      55 men) with mean age 56.4 were studied with three different low-dose protocols.
      The patients underwent an unenhanced and excretory low-dose phases and standard
      corticomedullary and nephrographic phases. Effective dose was reduced by more
      than 65 % using the 100-kV protocol and by more than 76 % with introduction of 80
      kV protocol. At the same time, patient images obtained with the new low-kV
      protocols maintained their diagnostic quality. 

PMID- 25848107
TI  - Digital breast tomosynthesis in one or two views as a replacement or adjunct
      technique to full-field digital mammography.
AB  - Clinical studies using different imaging protocols to perform digital breast
      tomosynthesis (DBT) were reviewed (2008-14) to assess interpretive accuracy.
      Descriptive pooled statistics were used to estimate and summarise accuracy
      measures for each type of imaging protocol in relation to that of two-view full
      field digital mammography (FFDM). In studies comparing multiple DBT imaging
      protocols, a trend of increased performance was often seen when including both
      the mediolateral oblique and craniocaudal views for DBT alone and even more so
      for DBT adjunct to FFDM. Overall, the average DeltaAUC (%; sd) across studies for
      stand-alone DBT (relative to FFDM), in one and in two views, were 2.2 (+/- 3.7)
      and 5.9 (+/- 4.6), and when used together with FFDM, 3.9 (+/- 2.0) and 6.7 (+/-
      0.9). With respect to individual studies, improvements in accuracy using DBT were
      present for different types of imaging protocols although the magnitude of the
      impact varied between studies, and some studies did not show significant
      improvements in comparison with FFDM. The most consistent effect of improvement
      in breast cancer detection was seen across studies for two-view DBT with FFDM.
      These summary findings may depend on the sampling constraints present in
      tomosynthesis imaging and on other factors discussed in this paper. In order to
      investigate these effects more thoroughly and how they might impact outcomes,
      comparative or randomized-controlled trials are warranted.

PMID- 25848108
TI  - Nanodosimetric track structure in homogeneous extended beams.
AB  - Physical aspects of particle track structure are important in determining the
      induction of clustered damage in relevant subcellular structures like the DNA and
      higher-order genomic structures. The direct measurement of track-structure
      properties of ionising radiation is feasible today by counting the number of
      ionisations produced inside a small gas volume. In particular, the so-called
      track-nanodosimeter, installed at the TANDEM-ALPI accelerator complex of LNL,
      measures ionisation cluster-size distributions in a simulated subcellular
      structure of dimensions 20 nm, corresponding approximately to the diameter of the
      chromatin fibre. The target volume is irradiated by pencil beams of primary
      particles passing at specified impact parameter. To directly relate these
      measured track-structure data to radiobiological measurements performed in broad
      homogeneous particle beams, these data can be integrated over the impact
      parameter. This procedure was successfully applied to 240 MeV carbon ions and
      compared with Monte Carlo simulations for extended fields. 

PMID- 25848109
TI  - Role of cardiac ultrafast cameras with CZT solid-state detectors and software
      developments on radiation absorbed dose reduction to the patients.
AB  - Myocardial perfusion imaging (MPI) is one the most contributing nuclear medicine
      technique to the annual population dose. The purpose of this study is to compare
      radiation-absorbed doses to the patients examined by conventional cardiac SPECT
      (CSPECT) camera and ultrafast cardiac (UFC) camera with cadmium-zinc-telluride
      (CZT) solid-state detectors. Total injected activity was reduced by 50 % when
      both stress and rest images were acquired and by 75 % when only stress images
      were taken with UFC camera. As a result of this, the mean total effective dose
      was found significantly lower with UFC camera (2.2 +/- 1.2 mSv) than CSPECT (7.7
      +/- 3.8 mSv) (p < 0.001). Further dose reduction was obtained by reducing
      equivocal test results and unnecessary additional examinations with UFC camera.
      Using UFC camera, MPI can be conveniently used for the detection of coronary
      artery disease (CAD) much less increasing annual population radiation dose as it
      had been before. 

PMID- 25848110
TI  - Looking into future: challenges in radiation protection in medicine.
AB  - Radiation protection in medicine is becoming more and more important with
      increasing wider use of X-rays, documentation of effects besides the potential
      for long-term carcinogenic effects. With computed tomography (CT) likely to
      become sub-mSv in coming years, positron emission tomography (PET), single photon
      emission computed tomography (SPECT) and some of the nuclear medical examination
      will become focus of attraction as high-dose examinations, even though they are
      less-frequent ones. Clarity will be needed on radiation effects at levels of
      radiation doses encountered in a couple of CT scans and if effects are really
      cumulative. There is challenge to develop radiation metrics that can be used as
      easily as units of temperature and length and avoidance of multiple meaning of a
      single dose metric. Other challenges include development of biological indicators
      of radiation dose, transition from dose to a representative phantom to dose to
      individual patient, system for tracking of radiation exposure history of patient,
      avoidance of radiation-induced skin injury in patients and radiation cataract in
      staff, cutting down inappropriate referrals for radiological examinations,
      confidence building in patient and patient safety in radiotherapy. 

PMID- 25848111
TI  - Patient radiation doses during coronary interventions in four Croatian hospitals:
      4-y comparison.
AB  - The number of coronary interventions increased substantially in the recent years.
      Although of great benefit to patients, these procedures can subject patients to
      considerable radiation doses. There is a legal framework for patient dose
      measurements in Croatia during radiological procedures, but in practice, it
      applies only occasionally. A quality control manual, established at the
      University Hospital Osijek, was accepted by other major cardiology centres in
      Croatia; besides checking the technical characteristics of the device, it
      provides constant measurement and analysis of patient doses in interventional
      cardiology. It also includes patient examination for radiation skin injuries in
      case of dose of >2 Gy. The aim of the study was to determine and compare patient
      radiation doses during cardiological interventions measured within 4 y in four
      major cardiology centres with the values proposed by the European Commission and
      other professional bodies. The local reference dose levels were also set. 

PMID- 25848112
TI  - An evaluation of the shielding effectiveness of lead aprons used in clinics for
      protection against ionising radiation from novel radioisotopes.
AB  - The purpose of this study is to evaluate the effectiveness of personal radiation
      shields currently worn in hospital and other diagnostic environments. This study
      was performed with four different radioisotopes; (18)F, (99m)Tc, (124)I and
      (131)I. (18)F results showed a decrease in dose with 0.5-mm Pb shielding but the
      reduction provided does not warrant its use clinically. (124)I testing
      demonstrated that dose enhancement can occur in greater shield thicknesses. PET
      isotope (124)I can be adequately shielded using 0.25-mm Pb equivalent aprons but
      any higher thickness increase the wearer's dose. As a result more shielding does
      not always equal more protection. The (131)I test showed that no dose reduction
      occurred, even when tested with up to 1.25-mm Pb equivalent shielding. Novel
      radioisotopes being used in the laboratory and clinic should be individually
      tested as each requires specific shielding testing. 

PMID- 25848113
TI  - Assessment of the occupational exposure in real time during interventional
      cardiology procedures.
AB  - Interventional cardiology (IC) procedures can be complex, requiring the operators
      to work near the patient, during long exposure times. Owing to scattered
      radiation in the patient and the fluoroscopic equipment, the medical staff are
      exposed to a non-uniform radiation field and can receive high radiation doses. In
      this study, it is proposed to analyse staff doses obtained in real time, during
      IC procedures. A system for occupational dosimetry in real time was used. In
      order to identify some parameters that may affect the staff doses, Monte Carlo
      (MC) calculations, using MCNPX v.2.7.0 code and voxel phantoms, were performed.
      The data obtained from measurements, together with MC simulations, allowed the
      identification of actions and behaviours of the medical staff that could be
      considered a risk under routine working conditions. The implementation of this
      monitoring system for exposure of personnel may have a positive effect on
      optimisation of radiological protection in fluoroscopically guided cardiac
      procedures. 

PMID- 25848114
TI  - How to use the equipment you have for appropriate quality at low radiation dose.
AB  - A CT department's ability to image with low radiation doses is determined
      primarily by the CT scan protocols and the radiologists' image quality
      expectations and to a lesser extent by the dose-reduction features available. The
      CT technology level has a smaller influence than might be expected. There are,
      however, exceptions where dose is directly linked to the scanner's technical
      capabilities. The key to appropriate image quality with low radiation dose is
      therefore optimised scan protocols. To optimise effectively, an in-depth
      understanding of the technical performance of the scanner is required. Therefore,
      optimisation is best carried out by a multi-disciplinary team that includes
      radiologists, technologists and medical physics experts. This article describes
      practical strategies for carrying out such exercises. 

PMID- 25848115
TI  - Collective effective dose in Europe from X-ray and nuclear medicine procedures.
AB  - Population doses from radiodiagnostic (X-ray and nuclear medicine) procedures in
      Europe were estimated based on data collected from 36 European countries. For X
      ray procedures in EU and EFTA countries (except Liechtenstein) the collective
      effective dose is 547,500 man Sv, resulting in a mean effective dose of 1.06 mSv
      per caput. For all European countries included in the survey the collective
      effective dose is 605,000 man Sv, resulting in a mean effective dose of 1.05 mSv
      per caput. For nuclear medicine procedures in EU countries and EFTA (except
      Liechtenstein) countries the collective effective dose is 30,700 man Sv,
      resulting in a mean effective dose of 0.06 mSv per caput. For all European
      countries included in the survey the collective effective dose is 31,100 man Sv,
      resulting in a mean effective dose of 0.05 mSv per caput.

PMID- 25848116
TI  - Paediatric CT protocol optimisation: a design of experiments to support the
      modelling and optimisation process.
AB  - In the last decade, several studies have emphasised the need to understand and
      optimise the computed tomography (CT) procedures in order to reduce the radiation
      dose applied to paediatric patients. To evaluate the influence of the technical
      parameters on the radiation dose and the image quality, a statistical model has
      been developed using the design of experiments (DOE) method that has been
      successfully used in various fields (industry, biology and finance) applied to CT
      procedures for the abdomen of paediatric patients. A Box-Behnken DOE was used in
      this study. Three mathematical models (contrast-to-noise ratio, noise and CTDI
      vol) depending on three factors (tube current, tube voltage and level of
      iterative reconstruction) were developed and validated. They will serve as a
      basis for the development of a CT protocol optimisation model.

PMID- 25848117
TI  - Estimation of staff lens doses during interventional procedures. Comparing
      cardiology, neuroradiology and interventional radiology.
AB  - The purpose of this article is to estimate lens doses using over apron active
      personal dosemeters in interventional catheterisation laboratories (cardiology
      IC, neuroradiology IN and radiology IR) and to investigate correlations between
      occupational lens doses and patient doses. Active electronic personal dosemeters
      placed over the lead apron were used on a sample of 204 IC procedures, 274 IN and
      220 IR (all performed at the same university hospital). Patient dose values
      (kerma area product) were also recorded to evaluate correlations with
      occupational doses. Operators used the ceiling-suspended screen in most cases.
      The median and third quartile values of equivalent dose Hp(10) per procedure
      measured over the apron for IC, IN and IR resulted, respectively, in 21/67, 19/44
      and 24/54 uSv. Patient dose values (median/third quartile) were 75/128, 83/176
      and 61/159 Gy cm(2), respectively. The median ratios for dosemeters worn over the
      apron by operators (protected by the ceiling-suspended screen) and patient doses
      were 0.36; 0.21 and 0.46 uSv Gy(-1) cm(-2), respectively. With the conservative
      approach used (lens doses estimated from the over apron chest dosemeter) we came
      to the conclusion that more than 800 procedures y(-1) and per operator were
      necessary to reach the new lens dose limit for the three interventional
      specialties. 

PMID- 25848118
TI  - Eye dosimetry and protective eyewear for interventional clinicians.
AB  - Doses to the eyes of interventional clinicians can exceed 20 mSv. Various
      protective devices can afford protection to the eyes with the final barrier being
      protective eyewear. The protection provided by lead glasses is difficult to
      quantify, and the majority of dosimeters are not designed to be worn under lead
      glasses. This study has measured dose reduction factors (DRFs) equal to the ratio
      of the dose with no protection, divided by that when lead glasses are worn.
      Glasses have been tested in X-ray fields using anthropomorphic phantoms to
      simulate the patient and clinician. DRFs for X-rays incident from the front vary
      from 5.2 to 7.6, while values for orientations reminiscent of clinical practice
      are between 1.4 and 5.2. Results suggest that a DRF of two is a conservative
      factor that could be applied to personal dosimeter measurements to account for
      the dose reduction provided by most types of lead glasses. 

PMID- 25848119
TI  - Dosimetry audit of radiotherapy treatment planning systems.
AB  - In radiotherapy Treatment Planning Systems (TPS) various calculation algorithms
      are used. The accuracy of dose calculations has to be verified. Numerous phantom
      types, detectors and measurement methodologies are proposed to verify the TPS
      calculations with dosimetric measurements. A heterogeneous slab phantom has been
      designed within a Coordinated Research Project (CRP) of the IAEA. The
      heterogeneous phantom was developed in the frame of the IAEA CRP. The phantom
      consists of frame slabs made with polystyrene and exchangeable inhomogeneity
      slabs equivalent to bone or lung tissue. Special inserts allow to position
      thermoluminescent dosimeters (TLD) capsules within the polystyrene slabs below
      the bone or lung equivalent slabs and also within the lung equivalent material.
      Additionally, there are inserts that allow to position films or ionisation
      chamber in the phantom. Ten Polish radiotherapy centres (of 30 in total) were
      audited during on-site visits. Six different TPSs and five calculation algorithms
      were examined in the presence of inhomogeneities. Generally, most of the results
      from TLD were within 5 % tolerance. Differences between doses calculated by TPSs
      and measured with TLD did not exceed 4 % for bone and polystyrene equivalent
      materials. Under the lung equivalent material, on the beam axis the differences
      were lower than 5 %, whereas inside the lung equivalent material, off the beam
      axis, in some cases they were of around 7 %. The TLD results were confirmed with
      the ionisation chamber measurements. The comparison results of the calculations
      and the measurements allow to detect limitations of TPS calculation algorithms.
      The audits performed with the use of heterogeneous phantom and TLD seem to be an
      effective tool for detecting the limitations in the TPS performance or beam
      configuration errors at audited radiotherapy departments. 

PMID- 25848120
TI  - Schizophrenia, Subjectivity, and Mindreading.
AB  - A number of recent articles, many appearing in Schizophrenia Bulletin, signal a
      renewed interest in phenomenological approaches to our understanding of
      schizophrenia. These approaches conceptualize schizophrenia as a disorder of
      altered self-awareness and decreased prereflective social attunement, which may
      manifest as an impaired understanding of self, others, and the physical world.
      Phenomenological approaches to psychopathology are sometimes construed as being
      incompatible with the reductionistic methodology of contemporary neuroscience. In
      this article, we re-examine findings from the phenomenological investigation of
      schizophrenia in light of an influential neurocomputational account of
      mindreading, which postulates that understanding of others is subserved by
      coherent internal self-models. We argue that the phenomenological approach to
      schizophrenia is not incompatible with a neurocomputational account of
      mindreading, and that the 2 approaches should instead be viewed as existing in a
      relationship of mutual constraint and enlightenment. Our hypothesis, while
      speculative, is an attempt to marry the phenomenological and neuronal realities
      of schizophrenia. Furthermore, it has implications for psychotherapeutic
      interventions and future research. 

PMID- 25848121
TI  - Tracking fusion of human mesenchymal stem cells after transplantation to the
      heart.
AB  - Evidence suggests that transplanted mesenchymal stem cells (MSCs) can aid
      recovery of damaged myocardium caused by myocardial infarction. One possible
      mechanism for MSC-mediated recovery is reprogramming after cell fusion between
      transplanted MSCs and recipient cardiac cells. We used a Cre/LoxP-based
      luciferase reporter system coupled to biophotonic imaging to detect fusion of
      transplanted human pluripotent stem cell-derived MSCs to cells of organs of
      living mice. Human MSCs, with transient expression of a viral fusogen, were
      delivered to the murine heart via a collagen patch. At 2 days and 1 week later,
      living mice were probed for bioluminescence indicative of cell fusion. Cell
      fusion was detected at the site of delivery (heart) and in distal tissues (i.e.,
      stomach, small intestine, liver). Fusion was confirmed at the cellular scale via
      fluorescence in situ hybridization for human-specific and mouse-specific
      centromeres. Human cells in organs distal to the heart were typically located
      near the vasculature, suggesting MSCs and perhaps MSC fusion products have the
      ability to migrate via the circulatory system to distal organs and engraft with
      local cells. The present study reveals previously unknown migratory patterns of
      delivered human MSCs and associated fusion products in the healthy murine heart.
      The study also sets the stage for follow-on studies to determine the functional
      effects of cell fusion in a model of myocardial damage or disease. SIGNIFICANCE:
      Mesenchymal stem cells (MSCs) are transplanted to the heart, cartilage, and other
      tissues to recover lost function or at least limit overactive immune responses.
      Analysis of tissues after MSC transplantation shows evidence of fusion between
      MSCs and the cells of the recipient. To date, the biologic implications of cell
      fusion remain unclear. A newly developed in vivo tracking system was used to
      identify MSC fusion products in living mice. The migratory patterns of fusion
      products were determined both in the target organ (i.e., the heart) and in distal
      organs. This study shows, for the first time, evidence of fusion products at
      sites distal from the target organ and data to suggest that migration occurs via
      the vasculature. These results will inform and improve future, MSC-based
      therapeutics.

PMID- 25848122
TI  - Bioengineering a human plasma-based epidermal substitute with efficient grafting
      capacity and high content in clonogenic cells.
AB  - Cultured epithelial autografts (CEAs) produced from a small, healthy skin biopsy
      represent a lifesaving surgical technique in cases of full-thickness skin burn
      covering >50% of total body surface area. CEAs also present numerous drawbacks,
      among them the use of animal proteins and cells, the high fragility of
      keratinocyte sheets, and the immaturity of the dermal-epidermal junction, leading
      to heavy cosmetic and functional sequelae. To overcome these weaknesses, we
      developed a human plasma-based epidermal substitute (hPBES) for epidermal
      coverage in cases of massive burn, as an alternative to traditional CEA, and set
      up critical quality controls for preclinical and clinical studies. In this study,
      phenotypical analyses in conjunction with functional assays (clonal analysis,
      long-term culture, or in vivo graft) showed that our new substitute fulfills the
      biological requirements for epidermal regeneration. hPBES keratinocytes showed
      high potential for cell proliferation and subsequent differentiation similar to
      healthy skin compared with a well-known reference material, as ascertained by a
      combination of quality controls. This work highlights the importance of
      integrating relevant multiparameter quality controls into the bioengineering of
      new skin substitutes before they reach clinical development. SIGNIFICANCE: This
      work involves the development of a new bioengineered epidermal substitute with
      pertinent functional quality controls. The novelty of this work is based on this
      quality approach.

PMID- 25848124
TI  - A Prorating Method for Estimating MMPI-2-RF Scores From MMPI Responses:
      Examination of Score Fidelity and Illustration of Empirical Utility in the
      PERSEREC Police Integrity Study Sample.
AB  - The purpose of the current study was to identify Minnesota Multiphasic
      Personality Inventory-2-Restructured Form (MMPI-2-RF) correlates of police
      officer integrity violations and other problem behaviors in an archival database
      with original MMPI item responses and collateral information regarding integrity
      violations obtained for 417 male officers. In Study 1, we estimated MMPI-2-RF
      scores from the MMPI item pool (which includes approximately 80% of the MMPI-2-RF
      items) in a normative sample, a psychiatric inpatient sample, and a police
      officer sample, and conducted analyses that demonstrated the comparability of
      estimated and full scale scores for 41 of the 51 MMPI-2-RF scales. In Study 2, we
      correlated estimated MMPI-2-RF scores with information about subsequent integrity
      violations and problem behaviors from the integrity violation data set. Several
      meaningful associations were obtained, predominately with scales from the
      emotional, thought, and behavioral dysfunction domains of the MMPI-2-RF.
      Application of a correction for range restriction yielded substantially improved
      validity estimates. Finally, we calculated relative risk ratios for the
      statistically significant findings using cutoffs lower than 65T, which is
      traditionally used to identify clinically significant elevations, and found
      several meaningful relative risk ratios. 

PMID- 25848125
TI  - Erratum.

PMID- 25848123
TI  - Concise Review: Macrophages: Versatile Gatekeepers During Pancreatic beta-Cell
      Development, Injury, and Regeneration.
AB  - Macrophages are classically considered detrimental for pancreatic beta-cell
      survival and function, thereby contributing to beta-cell failure in both type 1
      (T1D) and 2 (T2D) diabetes mellitus. In addition, adipose tissue macrophages
      negatively influence peripheral insulin signaling and promote obesity-induced
      insulin resistance in T2D. In contrast, recent data unexpectedly uncovered that
      macrophages are not only able to protect beta cells during pancreatitis but also
      to orchestrate beta-cell proliferation and regeneration after beta-cell injury.
      Moreover, by altering their activation state, macrophages are able to improve
      insulin resistance in murine models of T2D. This review will elaborate on current
      insights in macrophage heterogeneity and on the evolving role of pancreas
      macrophages during organogenesis, tissue injury, and repair. Additional
      identification of macrophage subtypes and of their secreted factors might
      ultimately translate into novel therapeutic strategies for both T1D and T2D.
      SIGNIFICANCE: Diabetes mellitus is a pandemic disease, characterized by severe
      acute and chronic complications. Macrophages have long been considered prime
      suspects in the pathogenesis of both type 1 and 2 diabetes mellitus. In this
      concise review, current insights in macrophage heterogeneity and on the, as yet,
      underappreciated role of alternatively activated macrophages in insulin sensing
      and beta-cell development/repair are reported. Further identification of
      macrophage subtypes and of their secreted factors might ultimately translate into
      novel therapeutic strategies for diabetes mellitus.

PMID- 25848126
TI  - Development and Validation of the Spiritual Care Needs Inventory for Acute Care
      Hospital Patients in Taiwan.
AB  - Spiritual care is increasingly being recognized as an integral aspect of nursing
      practice. The aim of this study was to develop a new instrument, Spiritual Care
      Needs Inventory (SCNI), for measuring spiritual care needs in acute care hospital
      patients with different religious beliefs. The 21-item instrument was completed
      by 1,351 adult acute care patients recruited from a medical center in Taiwan.
      Principal components analysis of the SCNI revealed two components, (a) meaning
      and hope and (b) caring and respect, which together accounted for 66.2% of the
      total variance. The internal consistency measures for the two components were
      0.96 and 0.91, respectively. Furthermore, younger age, female sex, Christian
      religion, and regularly attending religious activities had significantly higher
      mean total scores in both components. The SCNI was found to be a simple
      instrument with excellent internal consistency for measuring the spiritual care
      needs in acute care hospital patients.

PMID- 25848127
TI  - Effect of Acupressure on Maternal Anxiety in Women With Gestational Diabetes
      Mellitus: A Randomized Clinical Trial.
AB  - Women with diabetes often experience a higher level of anxiety. The aim of the
      study was to evaluate the effect of acupressure on relieving anxiety of women
      with gestational diabetes mellitus (GDM). A randomized clinical trial was
      conducted on 60 women with GDM at a university hospital. The participants were
      allocated to an experimental and a placebo group (30 women per group). The
      experimental group received a nurse-provided acupressure at the true point, and
      the placebo group received pressure (touching) at a sham (false) point. Anxiety
      was measured immediately in the groups prior to and after a 2-day intervention by
      a questionnaire and the Visual Analogue Scale. The data were analyzed using
      descriptive and inferential statistics. Results indicated that the acupressure
      group had significantly lower anxiety than the placebo group (p <= .0001). In
      conclusion, the effects of acupressure appeared to be effective in reducing
      anxiety in diabetic pregnant women. 

PMID- 25848129
TI  - Streptococcus pneumoniae-Associated Hemolytic and Uremic Syndrome With
      Cholestasis: A Case Report and Brief Literature Review.

PMID- 25848128
TI  - Correlates of Human Papillomavirus Vaccine Completion Among Adolescent Girl
      Initiators.
AB  - OBJECTIVE: To examine correlates of vaccine series completion among young
      adolescent US girls who initiated the human papillomavirus (HPV) vaccine.
      METHODS: We analyzed National Immunization Survey-Teens 2012 provider-verified
      data to examine correlates of HPV vaccine completion among 13- to 17-year-old
      girls who initiated HPV vaccine in 2012 (N = 4548). RESULTS: The weighted vaccine
      series completion rate among 13- to 17-year-old girl initiators was 66.7% (95%
      confidence interval [CI], 64.0-69.3). Adolescent girls who were older, residents
      of the Northeast (adjusted prevalence ratio [aPR], 1.36; 95% CI, 1.07-1.73), and
      had provider-verified seasonal influenza vaccination in the past year (aPR, 1.67;
      95% CI, 1.32-2.11) and provider recommendation (aPR, 1.40; 95% CI, 1.10-1.77)
      were more likely to complete the 3-dose vaccine series. CONCLUSIONS: Parents of
      younger adolescent girls need to be educated about the importance of completing
      the 3-dose HPV vaccine series. Provider recommendation for the vaccine would also
      facilitate series completion.

PMID- 25848130
TI  - Failure to Thrive and Respiratory Failure in an Adolescent Male.

PMID- 25848131
TI  - Effects of Rivaroxaban on Platelet Activation and Platelet-Coagulation Pathway
      Interaction: In Vitro and In Vivo Studies.
AB  - INTRODUCTION: Activation of coagulation and platelets is closely linked, and
      arterial thrombosis involves coagulation activation as well as platelet
      activation and aggregation. In these studies, we investigated the possible
      synergistic effects of rivaroxaban in combination with antiplatelet agents on
      thrombin generation and platelet aggregation in vitro and on arterial thrombosis
      and hemostasis in rat models. MATERIALS AND METHODS: Thrombin generation was
      measured by the Calibrated Automated Thrombogram method (0.5 pmol/L tissue
      factor) using human platelet-rich plasma (PRP) spiked with rivaroxaban (15, 30,
      or 60 ng/mL), ticagrelor (1.0 ug/mL), and acetylsalicylic acid (ASA; 100 ug/mL).
      Tissue factor-induced platelet aggregation was measured in PRP spiked with
      rivaroxaban (15 or 30 ng/mL), ticagrelor (1 or 3 ug/mL), or a combination of
      these. An arteriovenous (AV) shunt model in rats was used to determine the
      effects of rivaroxaban (0.01, 0.03, or 0.1 mg/kg), clopidogrel (1 mg/kg), ASA (3
      mg/kg), and combinations on arterial thrombosis. RESULTS: Rivaroxaban inhibited
      thrombin generation in a concentration-dependent manner and the effect was
      enhanced with ticagrelor and ticagrelor plus ASA. Rivaroxaban and ticagrelor also
      concentration-dependently inhibited tissue factor-induced platelet aggregation,
      and their combination increased the inhibition synergistically. In the AV shunt
      model, rivaroxaban dose-dependently reduced thrombus formation. Combining
      subefficacious or weakly efficacious doses of rivaroxaban with ASA or ASA plus
      clopidogrel increased the antithrombotic effect. CONCLUSION: These data indicate
      that the combination of rivaroxaban with single or dual antiplatelet agents works
      synergistically to reduce platelet activation, which may in turn lead to the
      delayed/reduced formation of coagulation complexes and vice versa, thereby
      enhancing antithrombotic potency.

PMID- 25848132
TI  - Effects of Pregnane X Receptor Genetic Polymorphisms on Stable Warfarin Doses.
AB  - OBJECTIVE: Pregnane X receptor (PXR) is a transcriptional regulator of many drug
      metabolizing enzymes including cytochrome P450 (CYP) 2C9. The objective of this
      study was to assess the possible association between PXR single-nucleotide
      polymorphisms (SNPs) and stable warfarin doses. METHODS: A total of 201 patients
      with stable warfarin doses from the EwhA-Severance Treatment (EAST) Group of
      Warfarin were included in this study. The influence of genetic polymorphisms on
      stable warfarin doses was investigated by genotyping 11 SNPs, that is, vitamin K
      epoxide reductase complex 1 (VKORC1) rs9934438, CYP2C9 rs1057910, CYP4F2
      rs2108622, constitutive androstane receptor (CAR) rs2501873, hepatocyte nuclear
      factor 4alpha (HNF4alpha) rs3212198, and PXR (rs3814055, rs1403526, rs3732357,
      rs3732360, rs2276707 and rs2472682). Subgroup analysis was conducted on CYP2C9
      wild-type homozygote allele (AA) carriers. RESULTS: One PXR SNP of rs2472682
      (A>C) exhibited significant association with stable warfarin doses in study
      population and the subgroup; variant homozygote carriers required significantly
      lower daily doses of warfarin than those carrying wild allele by about 0.8 mg.
      Approximate 43.7% of overall interindividual variability in warfarin dose
      requirement was explained by multivariate regression model. VKORC1, CYP2C9, age,
      CYP4F2, PXR rs2472682, and CAR/HNF4alpha rs2501873/rs3212198 accounted for 29.6%,
      5.9%, 3.7%, 2.3%, 1.3%, and 0.9% of the variability, respectively. PXR SNP of
      rs2472682 remained a significant factor in CYP2C9 wild-type homozygote carriers
      based on univariate and multivariate analyses. The combination of
      CAR/HNF4alpha/PXR SNPs of rs2501873/rs3212198/rs2472682 showed about 1 mg dose
      difference between grouped genotypes in study population and subgroup.
      CONCLUSION: Our results revealed that PXR could be a determinant of stable
      warfarin doses.

PMID- 25848133
TI  - First Metatarsophalangeal Joint Arthrodesis Technique With Interposition
      Allograft Bone Block.
AB  - BACKGROUND: We present a technique of first metatarsophalangeal joint arthrodesis
      utilizing an interposition allograft bone block with a bipolar reaming technique
      that creates congruent fusion surfaces on both ends of the graft-host bone
      interface. In addition, we examined the union rates, fusion position, patient
      satisfaction, and functional outcome of this technique. METHODS: Fifteen patients
      underwent first metatarsophalangeal joint arthrodesis with an interposition
      allograft bone block between September 2004 and October 2013. Charts and
      radiographs were reviewed. Six measures were compared on preoperative and
      postoperative radiographs. Clinical outcomes were measured using a telephone
      questionnaire, pre- and postoperative visual analog scale pain scale, and Foot
      and Ankle Ability Measure. Average follow-up was 46 weeks (range, 19 to 97).
      RESULTS: Thirteen of 15 (87%) patients achieved bony union at an average of 21
      weeks. One patient underwent revision arthrodesis for their nonunion. Symptomatic
      hardware was removed in 3 cases. Improvement was noted in visual analog scale
      pain scores (6 to 2) and functional scores as measured by the Foot and Ankle
      Ability Measure. There were no postoperative wound complications or infections.
      Average length of the first ray on anteroposterior radiograph increased from 10.7
      to 11.3 cm and from 10.0 to 10.7 cm on the lateral radiograph. Thirteen of 14
      patients were very satisfied or satisfied. One patient expressed dissatisfaction
      with the procedure. One patient was not available for clinical follow-up.
      CONCLUSION: First metatarsophalangeal joint allograft bone block arthrodesis
      using the bipolar reaming technique achieved high bony union rates and
      satisfactory radiographic and clinical outcomes. This procedure was an effective
      salvage option for managing bone loss on 1 or both sides of the joint. LEVEL OF
      EVIDENCE: Level IV, retrospective case series.

PMID- 25848134
TI  - Prospective Randomized Controlled Trial of Hindfoot and Ankle Fusions Treated
      With rhPDGF-BB in Combination With a beta-TCP-Collagen Matrix.
AB  - BACKGROUND: Ankle and hindfoot arthrodesis is often supplemented with autograft
      to promote bony union. Autograft harvest can lead to increased perioperative
      morbidity. Purified recombinant human platelet-derived growth factor BB homodimer
      (rhPDGF-BB) has stimulated bone formation in mandibular defects and hindfoot
      fusion. This randomized controlled trial evaluated the efficacy and safety of
      rhPDGF-BB combined with an injectable, osteoconductive beta-tricalcium phosphate
      (beta-TCP)-collagen matrix versus autograft in ankle and hindfoot fusions.
      METHODS: Seventy-five patients requiring ankle or hindfoot fusion were randomized
      5:1 for rhPDGF-BB/beta-TCP-collagen (treatment, n = 63) or autograft (control, n
      = 12). Prospective analysis included 142 autograft control subjects from another
      clinical trial with identical study protocols. Standardized operative and
      postoperative protocols were used. Patients underwent standard internal fixation
      augmented with autograft or 0.3 mg/mL rhPDGF-BB/beta-TCP-collagen. Radiologic,
      clinical, and quality-of-life outcomes were assessed over 52 weeks. Primary
      outcome was joint fusion (50% or more osseous bridging on computed tomography) at
      24 weeks. Secondary outcomes included radiographs, clinical healing status,
      visual analog scale pain score, American Orthopaedic Foot & Ankle Society Ankle
      Hindfoot Scale score, Foot Function Index score, and Short Form-12 score.
      Noninferiority P values were calculated. RESULTS: Complete fusion of all involved
      joints at 24 weeks as indicated by computed tomography was achieved in 53 of 63
      (84%) rhPDGF-BB/beta-TCP-collagen-treated patients and 100 of 154 (65%) autograft
      treated patients (P < .001). Mean time to fusion was 14.3 +/- 8.9 weeks for
      rhPDGF-BB/beta-TCP-collagen patients versus 19.7 +/- 11.5 weeks for autograft
      patients (P < .01). Clinical success at 52 weeks was achieved in 57 of 63 (91%)
      rhPDGF-BB/beta-TCP-collagen patients and 120 of 154 (78%) autograft patients (P <
      .001). Safety-related outcomes were equivalent. Autograft controls had 2 bone
      graft harvest infections. CONCLUSIONS: Application of rhPDGF-BB/beta-TCP-collagen
      was a safe, effective alternative to autograft for ankle and hindfoot fusions,
      eliminating the pain and morbidity associated with autograft harvesting. LEVEL OF
      EVIDENCE: Level I, prospective randomized study.

PMID- 25848135
TI  - Tibiotalocalcaneal Arthrodesis With an Intramedullary Hindfoot Nail and Pillar
      Fibula Augmentation: Technical Tip.

PMID- 25848136
TI  - Age and residency duration of loggerhead turtles at a North Pacific bycatch
      hotspot using skeletochronology.
AB  - For migratory marine animals, like sea turtles, effective conservation can be
      challenging because key demographic information such as duration of life stages
      and exposure to spatially explicit threats in different habitats are often
      unknown. In the eastern Pacific near the Baja California Peninsula (BCP), Mexico,
      tens of thousands of endangered North Pacific loggerhead sea turtles (Caretta
      caretta) concentrate at a foraging area known to have high rates of fishery
      bycatch. Because stage survivorship of loggerheads in the BCP will vary
      significantly depending on the number of years spent in this region, we applied
      skeletochronology to empirically estimate residency duration in this loggerhead
      hotspot. The observed age distribution obtained from skeletochronology analysis
      of 146 dead-stranded loggerheads ranged from three to 24 years old, suggesting a
      BCP residency of >20 years. Given the maximum estimated age and a one-year
      migration to western Pacific nesting beaches, we infer age-at-maturation for BCP
      loggerheads at ~25 years old. We also examine survivorship at varying BCP
      residency durations by applying our findings to current annual mortality
      estimates. Predicted survivorship of loggerheads spending over 20 years in this
      BCP foraging habitat is less than 10%, and given that ~43,000 loggerhead turtles
      forage here, a significant number of turtles are at extreme risk in this region.
      This is the first empirical evidence supporting estimated age-at-maturation for
      BCP North Pacific loggerheads, and the first estimates of BCP stage survivorship.
      Our findings emphasize the urgent need for continued and effective international
      conservation efforts to minimize bycatch of this endangered species.

PMID- 25848138
TI  - A Method to Determine the Density of Foods using X-ray Imaging.
AB  - Density of foods is an important physical property, which depends on structural
      properties of food. For porous foods such as baked foods, accurate measurement of
      density is challenging since traditional density measurement techniques are
      tedious, operator-dependent and incapable of precise volume measurement of foods.
      To overcome such limitations, a methodology was developed using both digital
      radiography(DR) and computed tomography(CT) x-ray imaging to directly determine
      density of foods. Apparent density was determined directly from x-ray linear
      attenuation coefficients by scanning at 40, 60, 80 kVp on DR and 45, 55, 70 kVp
      on CT. The apparent density can be directly determined using CT however sample
      thickness is needed to determine density using DR. No significant difference
      (p<0.05) was observed between density obtained from traditional methods, with
      density determined from x-ray linear attenuation coefficients. Density determined
      on CT for all foods with mean 0.579 g/cm3 had a standard deviation, SD = 0.0367
      g/cm3. Density determination using x-ray linear attenuation was found to be a
      more efficient technique giving results comparable with conventional techniques.

PMID- 25848137
TI  - Wrinkled, wavelength-tunable graphene-based surface topographies for directing
      cell alignment and morphology.
AB  - Textured surfaces with periodic topographical features and long-range order are
      highly attractive for directing cell-material interactions. They mimic
      physiological environments more accurately than planar surfaces and can
      fundamentally alter cell alignment, shape, gene expression, and cellular assembly
      into superstructures or microtissues. Here we demonstrate for the first time that
      wrinkled graphene-based surfaces are suitable as textured cell attachment
      substrates, and that engineered wrinkling can dramatically alter cell alignment
      and morphology. The wrinkled surfaces are fabricated by graphene oxide wet
      deposition onto pre-stretched elastomers followed by relaxation and mild thermal
      treatment to stabilize the films in cell culture medium. Multilayer graphene
      oxide films form periodic, delaminated buckle textures whose wavelengths and
      amplitudes can be systematically tuned by variation in the wet deposition
      process. Human and murine fibroblasts attach to these textured films and remain
      viable, while developing pronounced alignment and elongation relative to those on
      planar graphene controls. Compared to lithographic patterning of nanogratings,
      this method has advantages in the simplicity and scalability of fabrication, as
      well as the opportunity to couple the use of topographic cues with the unique
      conductive, adsorptive, or barrier properties of graphene materials for
      functional biomedical devices.

PMID- 25848139
TI  - Extensive complex odontoma in the maxillary sinus pushing 3rd molar near the
      orbital floor causing transient diplopia and chronic sinusitis: a rare
      presentation and surgical management.
AB  - Odontoma is a mixed odontogenic hamartoma involving both epithelial and
      mesenchymal tissues. If left untreated, it can lead to complications in certain
      conditions. Here is a rare presentation of an extensive complex odontoma in
      maxillary sinus pushing third molar near the orbital floor causing transient
      diplopia in upward gaze occasionally and chronic sinusitis. Although odontomata
      are not uncommon and are familiar to practitioners, but some aggressive cases may
      cause problematic sequelae. Even postoperative complications may result if oral
      surgeons are not aware of the potential pitfalls associated with the surgical
      removal of large maxillary antrum odontomata. This article reports a rare
      presentation which can be considered unique because when obstruction of sinus
      drainage is evident, serious complications such as orbital infections, epidural
      and subdural empyema, meningitis, cerebritis, cavernous sinus thrombosis, brain
      abscess and death can occur. It also addresses points and pitfalls concerning
      surgery to remove odontoma. 

PMID- 25848140
TI  - 'Potato peel dressing': a novel adjunctive in the management of necrotizing
      fasciitis.
AB  - Management of necrotizing fasciitis, a rare and potentially fatal, polymicrobial
      disease comprises of aggressive debridement, intravenous antibiotics and
      application of various adjunctives. So far adjunctives like hyperbaric oxygen
      therapy, intravenous immunoglobulins, vacuum assisted or foam dressing, and
      guided tissue regeneration with amniotic dressing have been put to use. Each of
      these adjunctives has faced criticism for their shortcomings. Potato peel has
      been used as a dressing for chronic wounds but there is no literature available
      on its application over wounds afflicted with necrotizing fasciitis. Owing to
      various medicinal properties of potato peel and its use as a dressing in other
      medical conditions, same was used as an adjunctive in the present case. Here we
      present a case of cervical necrotizing fasciitis of dentogenous origin, treated
      by mainstay surgical treatment with debridement, drainage in combination with
      broad spectrum antibiotics and a novel adjunctive, 'potato peel dressing', which
      has shown promising results. 

PMID- 25848141
TI  - Potentially fatal supramylohyoid sublingual epidermoid cyst.
AB  - A case of chronic and slow growing massive lateral neck swelling is presented
      which gradually resulted in dysphagia to an extent that patient reported in
      emergency room. Clinical findings were indicative of a cystic swelling or a
      massive lipoma. Temporary decompression of the lesion was achieved by partially
      aspirating the contents of the cyst. Nature of aspirate and its microscopic and
      biochemical analysis excluded lipoma, vascular malformation and salivary
      phenomenon. The diagnosis tapered to developmental lateral neck cysts. Magnetic
      Resonance Imaging (MRI) revealed a massive cystic lesion in the left floor of
      mouth extending to the right lingual aspect of mandible and posteriorly to
      impinge on the medial wall of pharynx. A combined intraoral and extraoral
      approach was used to expose and excise the lesion in toto. Final histological
      diagnosis of the pathology was epidermoid cyst. 

PMID- 25848142
TI  - Eagle's Syndrome: A New Surgical Technique for Styloidectomy.
AB  - The purpose of this paper is to discuss the current diagnosis of Eagle's syndrome
      (elongated styloid process) and to discuss a new and a much simpler technique for
      styloidectomy with an intraoral approach which can be used in local anesthesia.
      Easiness to perform, non-association of any anesthetic complications and
      avoidance of an extraoral scar dictates that this approach can be practiced much
      safely in patients with elongated styloid process. 

PMID- 25848143
TI  - Hemiatrophy of the tongue caused by an extensive vagus nerve schwannoma
      masquerading as a carotid chemodectoma.
AB  - BACKGROUND: Carotid chemodectomas or carotid body tumors are rare neoplasms,
      generally benign and frequently asymptomatic, which represent 0.6 % of all head
      and neck tumours. Schwannomas or neurilemmomas are benign, slow growing tumours
      that derive from the sheath of peripheral and cranial nerves. Of all
      neurilemmomas, 25-45 % originate from the head and neck region, with the vagus
      nerve being one the most encountered sites of occurrence. CASE REPORT: We
      describe a schwannoma originating from the vagus nerve mimicking a carotid body
      tumour and compromising the function of the hypoglossal nerve. DISCUSSION:
      Patients with lateral neck masses near the bifurcation of the carotid artery are
      often referred to the maxillofacial surgeon. The differential diagnosis of these
      lesions includes a variety of tumours among which carotid chemodectomas and vagus
      nerve schwannomas have a significant incidence. Both lesions may appear as
      completely asymptomatic, thus it is very difficult to identify the origin of the
      tumour based on physical examination. In making a differential diagnosis of the
      cervical tumours imaging studies play a key role. PURPOSE: A diagnostic algorithm
      based on contemporary imaging modalities, which can be useful in order to
      distinguish between these two pathological entities is presented.

PMID- 25848144
TI  - Collision tumor of maxilla: a diagnostic dilemma.
AB  - Most malignant tumors arise from the primary tissue except when showing extreme
      dedifferentiation. This can be identified by examination of tumor cells and their
      products. Occasionally two distinct tissues are recognized within a malignant
      tumor. In mixed malignant tumors both carcinomatous and sarcomatous elements are
      present either because of simultaneous malignant change occurring in the
      epithelium and its nonepithelial stroma or there is a sarcomatous transformation
      of stroma of a carcinoma. Willey's in 1960 stated that in these circumstances the
      resulting tumor must be classified as a "carcino-sarcoma". These separate tumors
      arise in nearby structures and may grow to infiltrate in each other resulting in
      a tumor mass. The present article is a report of a diagnostic dilemma in an
      extremely rare carcinosarcoma of maxilla in a 24 year old male which was first on
      biopsy reported as odontogenic myxoma. After resection (right maxillectomy under
      GA using Weber Fergusons approach with Diffenbach's extension) was diagnosed as
      Squamous Cell Carcinoma arising from lining of the maxillary antrum associated
      with Osteogenic Sarcoma (chondroblastic differentiation) of maxilla with negative
      margins. The tumor was restaged to T2NoMx and further managed as per National
      Comprehensive Cancer Network Guidelines. Immunohistochemistry later re-diagnosed
      it to be an Osteogenic Sarcoma maxilla with chondroblastic differentiation. 'T'
      stage remains the most reliable predictor of survival and loco-regional control.
      Complete surgical resection for all 'T' stages (except T4b, any N) followed by
      postoperative therapy remains a corner stone of treatment of maxillary sinus
      tumors. 

PMID- 25848145
TI  - Tissue expanders in reconstruction of maxillofacial defects.
AB  - Tissue expansion in its natural ways had fascinated man from prehistoric times
      itself. But tissue expansion for medical purposes was first tried and reported
      only in the early half of twentieth century. Presently the principle of tissue
      expansion is being used in reconstruction of many hard and soft tissue defects of
      larger dimension, which were previously regarded as great challenge for
      maxillofacial and plastic surgeons. Making use of the viscoelastic nature of the
      skin, considerable amount of tissue expansion based tissue engineering is
      possible in the maxillofacial region. Here we present a case of a facial scar of
      large dimension with a central oro cutaneous fistula developed as a result of
      facial artery blow out in a 24 year old female for which esthetic correction was
      done using the excess tissue obtained from tissue expansion. In this case where
      other methods of reconstruction such as local flaps, free flaps and normal tissue
      grafts were assessed to be non viable, tissue expansion was found to be an apt
      solution for esthetic reconstruction. 

PMID- 25848146
TI  - Amniotic membrane as a biological scaffold after vestibuloplasty.
AB  - Vestibuloplasty techniques are widely carried out to make the denture bearing
      area more suitable and adequate to receive the intended prosthesis. One of the
      major challenges after a vestibuloplasty procedure is to reduce post operative
      discomfort, scar contracture and subsequent loss in sulcular depth. A raw bony
      surface, as is obtained after Clark's vestibuloplasty is prone not only to
      infections and increased pain, but also to increased scarring during the healing
      phase. Skin grafts have been most commonly used to cover the exposed periosteal
      surface but they have their own disadvantages. There is a constant search for
      biocompatible membranes/materials which would satisfy most criteria required of a
      biological scaffold. Amnion is the innermost layer of the placenta with certain
      unique properties. Here we discuss the efficacy of amniotic membrane as a
      biological dressing after vestibuloplasty. 

PMID- 25848147
TI  - Sicca syndrome and dementia in a patient with hepatitis C infection: a case
      report with unusual bifocal extrahepatic manifestations.
AB  - INTRODUCTION: Hepatitis C virus (HCV) infections are associated with extrahepatic
      manifestations in 40-75 % of cases. Sialitis and secondary Sjogren syndrome are
      well characterized complications of chronic HCV infections but the mechanisms
      (primary or secondary) leading to xerostomia are not understood. Similarly, brain
      lesions due to HCV can be primary or secondary but the pathology of primary HCV
      related brain lesions is not well described. CASE REPORT: We report the
      postmortem case of a 60-year old patient initially presenting with sicca syndrome
      and dementia. HCV was identified in the brain but not in the salivary glands
      using transcription-mediated amplification (TMA). Focal sialitis was found in
      submandibular glands. Neuropathological examination revealed the presence of
      multiple dot-sized demyelination foci. CONCLUSION: Sicca syndrome is a common
      concern in chronic HCV infections and may be due to secondary immune mechanisms
      (we could not isolate HCV in salivary gland tissues). TMA had never been applied
      to the detection of viruses in salivary glands and neural tissues and proves to
      be a promising technique. Neuropathological reports in HCV infections are rare
      and the lesions we report may be the first characterization of the direct effect
      of HCV on brain cells. More cases are needed to define the full spectrum of
      lesions potentially caused by the direct action of the HCV on salivary glands and
      neural tissues.

PMID- 25848148
TI  - Multiple verrucous carcinomas of the oral cavity.
AB  - The author herein reports a case of multiple verrucous carcinomas (VCs) of the
      left lower gingiva. A 78-year-old man was admitted to our hospital because of
      gingival tumor. A biopsy revealed severe dysplasia. Surgical resection was
      performed. Grossly, there were three verrucous lesions (25, 20, 10 mm) in the
      left lower gingiva. Histologically, 2 tumors (4, 2 mm) were found in addition to
      the grossly visible 3 tumors. All the 5 tumors were VCs. The tumors showed
      verrucous and papillary proliferation of squamous epithelium with little cellular
      atypia. No invasive features were recognized. The dermis showed lymphocytic
      infiltration. The surrounding mucosa showed many broad foci of squamous cell
      carcinoma in situ and severe dysplasia (high grade intraepithelial neoplasm).
      Gradual merges between the VCs and squamous cell carcinoma in situ or severe
      dysplasia were frequently recognized. Immunohistochemically, the VC tumor cells
      and squamous lesions were negative for human papilloma virus antigens. P53
      protein was expressed in all the VCs and squamous epithelial lesions: it was
      accentuated in the basal and suprabasal cells of VC. Ki-67 antigen was also
      expressed in the 5 VCs and in the squamous lesion, and Ki-67 labeling index
      ranged from 8 to 16 % in VC and from 37 to 62 % in the squamous lesions. These
      data support the multicentric nature of VC and that the severe dysplasia
      carcinoma in situ sequence have been proposed in the etiology of VC. 

PMID- 25848149
TI  - Vascular transformation of bilateral cervical lymph node sinuses: a rare entity
      masquerading as tumor recurrence.
AB  - Vascular transformation of sinuses (VTS) is a rare and reactive vasoproliferative
      disorder infrequently affecting the cervical lymph nodes. It is characterized by
      effacement of nodal architecture by variable expansion of the subcapsular,
      intermediate, and medullary sinuses. We report a very rare and unique case of VTS
      in bilateral cervical lymph nodes along with angiolipomatous hamartoma in a
      postoperative patient of squamous cell carcinoma of buccal mucosa clinically
      masquerading as tumor recurrence. To the best of our knowledge, only 15 cases of
      VTS have been reported in cervical lymph nodes till date and associated
      angiolipomatous or angiomyomatous hamartoma-like area was noted only in two cases
      of cervical lymph node VTS. 

PMID- 25848150
TI  - Giant osteochondroma of the coronoid process.
AB  - Osteochondroma or solitary osteocartilagenous exostosis is characterized by
      cartilage-capped osseous lesion, protruding from the surface of affected bone. It
      is one of the most common benign bone tumor in axial skeleton and infrequent in
      maxillofacial skeleton. This paper describes a giant osteochondroma of coronoid
      process in a 20 year old woman, presented with limited mouth opening (15 mm inter
      incisal distance) and pain without any facial swelling, asymmetry and TMJ
      problems. Based on clinical examination, panoramic radiography and computed
      tomography images a provisional diagnosis of osteoma or osteochondroma of the
      coronoid process was made. Under general anaesthesia through intra oral approach
      excision of the bony tumor along with the coronoid process was performed, with
      recovery of mouth opening up to 40 mm immediately following surgery. The
      histopathology of excised specimen revealed features suggestive of
      osteochondroma. After follow up period of 54 months patient is symptom free. Here
      we are presenting and discussing the complete diagnostic and treatment aspect of
      this unusually large osteochondroma of coronoid process of mandible. 

PMID- 25848151
TI  - Pseudotumour of the Mandible Associated with von Willebrand's Disease.
AB  - Patients with bleeding disorders may occasionally present with pseudotumours.
      Most commonly these occur in the soft tissues and long bones, and are very rare
      in the maxillofacial region. We present the clinical details and management of a
      pseudotumour of the mandible in a 12-year-old girl with von Willebrand's disease.

PMID- 25848152
TI  - The karapandzic flap in lower lip reconstruction.
AB  - Human bite injuries are both deceptive and challenging in their presentation and
      management. They are particularly notorious due to the polymicrobial nature of
      human saliva inoculated in the wound and the risk they pose for transmission of
      infectious diseases. Early treatment, appropriate prophylaxis and surgical
      evaluation are the key to achieving desired treatment outcomes. Here we present a
      case report of human lip bite with significant tissue loss that required
      reconstruction. The reconstructive techniques are usually varied but the ultimate
      objectives of treatment are to achieve healing, function, and aesthetics. Through
      this article, we have tried to focus on the diagnostic features, reconstructive
      procedure as well as other recommended treatment options for human lip bites
      based on the current available evidence. 

PMID- 25848153
TI  - Traumatic herniation of buccal fat pad in 1 year old child: case report and
      review of literature.
AB  - Traumatic herniation of buccal fat pad (BFP) is very rare, usually seen in
      infants and young children ranging from 5 months to 12 years of age. Etiology
      will be blunt injury to buccal mucosa from foreign objects or trauma due to teeth
      and fall. The suckling activity in infants may also encourage the herniation
      following trauma. A minor injury or perforation to the buccal mucosa can cause
      herniation of BFP. The size of herniated mass is very large when compared to the
      size of the perforation. The history of trauma, absence of prolapse before the
      injury, its occurrence in infants and young children, specific anatomic sites and
      location of perforation in mucosa, histopathological appearance of adipose tissue
      are the characteristic features important for diagnosing the condition. The
      treatment options for the herniated BFP are usually excision. Alternative to
      excision is repositioning of the herniated fat in its anatomical location if
      noticed early. 

PMID- 25848154
TI  - Salivary gland tumors: a diagnostic dilemma!
AB  - Salivary gland tumors generate considerable interest because of their
      heterogeneous and variable histology, grade of malignancy, and clinical behavior.
      Fine needle aspiration cytology (FNAC) is considered the first diagnostic
      modality for salivary neoplasms due to its ready availability and ease of
      performance. However it cannot always be relied upon in isolation, and should be
      used in conjunction with other investigations like incisional biopsy. We present
      two cases, which highlight the drawbacks of relying on FNAC alone, which resulted
      in misdiagnosis of adenoid cystic carcinoma as pleomorphic adenoma. 

PMID- 25848155
TI  - Bilateral glandular odontogenic cyst of mandible: a rare occurrence.
AB  - Glandular odontogenic cysts (GOCs) of the jaw are rare with well-defined limits
      radiologically, unusual histopathological features and a high recurrence rate.
      The radiographic appearance of GOCs vary and are not pathognomonic. Definitive
      diagnosis of the GOC is established only by histopathological examinations.
      Histologically, GOC is characterized by a thin nonkeratinized squamous epithelial
      lining, with papillary projections, nodular thickenings, mucous (goblet) cells
      with intraepithelial mucous pools and intraepithelial glandular, microcystic or
      duct-like structures. We present an unusual case of a bilateral GOC in the
      mandible. This case report is also the first documented case of bilateral GOC in
      the mandible. 

PMID- 25848156
TI  - A Case of Oro-antral Communication Closed by Autotransplantation of Third Molar.
AB  - A number of surgical treatment modalities have been described in literature for
      closure of oro-antral communications. None of the methods however provide for
      immediate prosthetic rehabilitation of the communication site. We describe a case
      of oro-antral communication treated using autogenous third molar transplantation.
      At 18 months of follow-up, the transplanted tooth was functioning well with
      radiographic evidence of lamina dura and periodontal ligament. Its root-tip was
      still seen projecting into the maxillary sinus. This report suggests that when
      possible, autotransplantation of third molar can be a simple and excellent choice
      for closure of oro-antral communications. 

PMID- 25848157
TI  - Recurrence of a giant peripheral osteoma of mandible.
AB  - Osteomas are rare benign tumours in the bone. We describe a case of giant osteoma
      involving the lingual side of the ramus and body of mandible that recurred 8
      years after its surgical treatment at another hospital. Surgical resection with
      reconstruction is the treatment of choice for this lesion. The
      clinicopathological features of osteoma are discussed and Gardner's syndrome was
      excluded. 

PMID- 25848158
TI  - Septo-optic Dysplasia Complex with Omphalocele, Pre-maxillary Agenesis and
      Encephalocele.
AB  - Septo-optic dysplasia complex (SODC) is a rare congenital anomaly, characterized
      with absence of septum pellucidum, optic nerve hypoplasia with or without
      pituitary dysfunction. Various midline defects are also associated with SODC in
      addition to its classical findings. We report, for the first time a rare
      presentation of SODC which is associated with pre-maxillary agenesis along with
      sphenoidal encephalocele and omphalocele. The case showed resulting median cleft
      lip and palate along with other multiple congenital defects including hydrocele,
      inguinal hernia, micropenis and a wide mediastinum. 

PMID- 25848159
TI  - MRI as an essential diagnostic approach for trigeminal neuralgia.
AB  - Trigeminal neuralgia is a well recognised disorder frequently reported to the
      dentist. The diagnosis of trigeminal neuralgia is primarily based on history and
      clinical criteria. The clinical findings do not differentiate idiopathic
      trigeminal neuralgia from symptomatic trigeminal neuralgia. We describe a case of
      cliviopetrosal meningioma presenting as trigeminal neuralgia and discuss the
      importance of magnetic resonance imaging as an essential diagnostic approach when
      trigeminal neuralgia occurs concurrently with a brain tumour. 

PMID- 25848160
TI  - Neurofibroma of facial nerve presenting as parotid mass.
AB  - Neurogenic neoplasms presenting as parotid gland tumors are extremely uncommon.
      We present the case of a solitary neurofibroma of the facial nerve within the
      parotid gland occurring in a 36-year-old male who presented with a painless
      enlargement in the right-side region of the parotid gland over a period of 1 year
      with normal facial nerve function. Magnetic resonance imaging revealed a well
      demarcated round mass within the right parotid. At surgery, a tumor was found
      involving the main trunk of the facial nerve, histopathologically representing a
      neurofibroma. 

PMID- 25848161
TI  - Conservative treatment protocol of keratocystic odontogenic tumor: report of a
      case with nevoid Basal cell carcinoma syndrome and literature review.
AB  - Keratocystic odontogenic tumor (KOT) is one of the major components of nevoid
      basal cell carcinoma syndrome (NBCCS), which usually occurs in young ages and
      includes significant structures of jaws. According to high recurrence rate of
      KOT, there are many controversies in treatment of the lesion, especially in
      syndromic cases with younger ages. In current report, authors suggest a
      conservative protocol in the treatment of KOT in a patient with NBCCS. 

PMID- 25848162
TI  - Facial translocation approach for management of invasive sinonasal aspergillosis.
AB  - Aspergillosis is an uncommon fungal disease seen commonly in paranasal sinuses.
      It may be of noninvasive variety which is restricted to paranasal sinuses seen in
      healthy and immunocompetent hosts or may present as invasive form seen in
      immunocompromised hosts especially in diabetics and patients under long term
      immunosuppressant therapy. Along with paranasal sinuses invasive forms may
      encroach upon surrounding adjacent structures involving the orbit and extend
      intracranially. Orbital and intracranial involvement have a high mortality rate.
      Early diagnosis of the lesion and prompt aggressive management is important for
      better prognosis. Aggressive treatment includes surgical debulking and medical
      management mainly with systemic amphotericin B and other azoles. In orbito
      cranial involvement, due to limited access to cranial base, it becomes difficult
      to surgically debulk the lesion with safety to surrounding important structures.
      Facial translocation approach gives adequate access to paranasal sinuses, orbit
      and anterior cranial base. Reported here are two cases of invasive cranio-orbito
      nasal aspergillosis treated with facial translocation approach. 

PMID- 25848163
TI  - Challenges in Health Research Funding: an opinion.

PMID- 25848164
TI  - Neutralization function affected by single amino acid replacement in the HIV-1
      antibody targets.
AB  - The viral envelope glycoproteins are essential for entry into their host cells
      and studied extensively for designing vaccines. We hypothesize that the
      glycosylation on the HIV-1 viral envelope glycoprotein 41(gp41) at critical
      residues offers viral escape from the specific immune surveillant neutralizing
      antibodies Z13, 4E10 and 10E8 targeted to their linear epitopes in the Membrane
      Proximal External Region (MPER). The glycosylation occurring on the 50th residue
      (Asparagine) contained in the target (NWFNIT) can mask itself to be inaccessible
      for these neutralizing antibodies. The glycosylation rate of the epitopes which
      are shared by the Z13, 4E10 and 10E8 neutralizing antibodies of HIV-1 were
      predicited in silico. We analyzed the reliable frequency of glycosylation on the
      HIV-1 envelope gp41 using prediction tools to unravel the plausibility of the
      glycosylation by a mannose at 50th residue in the 59 amino acid long HIV-gp41
      trimer (PDBID: 2M7W and 2LP7). It is evident that the glycosylation by a mannose
      that masks these targets is possible only when the 50th amino-acid is N
      (Asparagine, Asn) which is not possible when N is mutated to D (Aspartatic acid,
      Asp). The additive advantage for the retrovirus is its error-prone reverse
      transcriptase which can choose to copy these survivable mutants with Asn N-50
      that can be glycosylated as explained by the Copy-choice model. So the glycan
      shields varying in their intensity and patterns have to be essentially studied to
      understand the viral escape strategies that will give a way forward towards a
      successful vaccine that can elicit a neutralizing antibody response to confer
      protection. 

PMID- 25848165
TI  - Pharmacophore elucidation and molecular docking studies on phosphodiesterase-5
      inhibitors.
AB  - cGMP-binding cGMP-specific PDE, PDE5 plays a key role in the hydrolysis of cyclic
      guanidine monophosphate. Because cGMP mediates vascular functions, a PDE5
      inhibitor that elevates cGMP level is an attractive means for vasodilatation and
      treatment of erectile dysfunction. In this paper we report the elucidation of the
      common pharmacophore hypothesis of different classes of PDE5 inhibitors. Using
      LigandScout program, pharmacophore modelling studies were performed on prior
      reported potent PDE5 inhibitors with a variety of scaffolds in order to identify
      one common set of critical chemical features of these PDE5 inhibitors 1-52. The
      best pharmacophore model, model-1, characterized by four chemical features: one
      aromatic ring, one hydrophobe, one hydrogen acceptors and one hydrogen donor.
      Using Dock6 program, docking studies were performed in order to investigate the
      mode of binding of these compounds. The molecular docking study allowed
      confirming the preferential binding mode of different classes of PDE5 inhibitors
      inside the active site. The obtained binding mode was as same as that of
      vardenafil, X-ray ligand with different orientation with varied PDE5 inhibitors'
      scaffold. 

PMID- 25848166
TI  - Comparative sequence-structure analysis of Aves insulin.
AB  - Normal blood glucose level depends on the availability of insulin and its ability
      to bind insulin receptor (IR) that regulates the downstream signaling pathway.
      Insulin sequence and blood glucose level usually vary among animals due to
      species specificity. The study of genetic variation of insulin, blood glucose
      level and diabetics symptoms development in Aves is interesting because of its
      optimal high blood glucose level than mammals. Therefore, it is of interest to
      study its evolutionary relationship with other mammals using sequence data.
      Hence, we compiled 32 Aves insulin from GenBank to compare its sequence-structure
      features with phylogeny for evolutionary inference. The analysis shows long
      conserved motifs (about 14 residues) for functional inference. These sequences
      show high leucine content (20%) with high instability index (>40). Amino acid
      position 11, 14, 16 and 20 are variable that may have contribution to binding to
      IR. We identified functionally critical variable residues in the dataset for
      possible genetic implication. Structural models of these sequences were developed
      for surface analysis towards functional representation. These data find
      application in the understanding of insulin function across species. 

PMID- 25848167
TI  - In silico pharmacokinetic and molecular docking studies of small molecules
      derived from Indigofera aspalathoides Vahl targeting receptor tyrosine kinases.
AB  - Angiogenesis is the formation of new blood vessels from preexisting vascular
      network that plays an important role in the tumor growth, invasion and
      metastasis. Anti-angiogenesis targeting tyrosine kinases such as vascular
      endothelial growth factor receptor 2 (VEGFR2) and platelet derived growth factor
      receptor beta (PDGFRbeta) constitutes a successful target for the treatment of
      cancer. In this work, molecular docking studies of three bioflavanoid such as
      indigocarpan, mucronulatol, indigocarpan diacetate and two diterpenes namely
      erythroxydiol X and Y derived from Indigofera aspalathoides as PDGFRbeta and
      VEGFR2 inhibitors were performed using computational tools. The crystal
      structures of two target proteins were retrieved from PDB website. Among the five
      compounds investigated, indigocarpan exhibited potent binding energy DeltaG = 
      7.04 kcal/mol with VEGFR2 and DeltaG = -4.82 with PDGFRbeta compared to
      commercially available anti-angiogenic drug sorafenib (positive control). Our
      results strongly suggested that indigocarpan is a potent angiogenesis inhibitor
      as ascertained by its potential interaction with VEGFR2 and PDGFRbeta. This
      hypothesis provides a better insight to control metastasis by blocking
      angiogenesis. 

PMID- 25848168
TI  - High quality SNPs/Indels mining and characterization in ginger from ESTs data
      base.
AB  - Ginger (Zingiber officinale Rosc.) is an important herb of the family
      Zingiberaceae. It is accepted as a universal cure for a multitude of diseases in
      Indian systems of medicine and its rhizomes are equally popular as a spice
      ingredient throughout Asia. SNPs, the definitive genetic markers, representing
      the finest resolution of a DNA sequence, are abundantly found in populations
      having a lower rate of mutation and are used for genomic analysis. The public
      ESTs sequences mostly lack quality files, making high quality SNPs detection more
      difficult since it is exclusively based on sequence comparisons. In the present
      study, current dbESTs of NCBI was mined and 38115 ginger ESTs sequences were
      obtained and assembled into contigs using CAP3 program. In this analysis, recent
      software tool QualitySNP was used to detect 11523 potential SNPs sites, 8810 high
      quality SNPs and 1008 indels polymorphisms with a frequency of 1.61 SNPs / 10
      kbp. Of ESTs libraries generated from three ginger tissues together, rhizomes had
      a frequency of 0.32 SNPs and 0.03 indels per 10 kbp whereas the leaves had a
      frequency of 2.51 SNPs and 0.23 indels per 10 kbp and root is showing relative
      frequency of 0.76/10 kbp SNPs and 0.02/10 kbp indels. The present analysis
      provides additional information about the tissue wise presence of haplotypes
      (222), distribution of high quality exonic (2355) and intronic (6455) SNPs and
      information about singletons (7538) in addition to contigs transitions and
      transversions ratio (0.57). Among all tissue detected SNPs, transversions number
      is higher in comparison to the number of transitions. Quality SNPs detected in
      this work can be used as markers for further ginger genetic experiments. 

PMID- 25848169
TI  - Application of centrality measures in the identification of critical genes in
      diabetes mellitus.
AB  - The connectivity of a protein and its structure is related to its functional
      properties. Many experimental approaches have been employed for the
      identification of Diabetes Mellitus (DM) associated candidate genes. Therefore,
      it is of interest to use var ious graph centrality measures integrated with the
      genes associated with the human Diabetes Mellitus network for the identification
      of potential targets. We used 2728 genes known to cause Diabetes Mellitus from
      Jensenlab (Novo Nordisk Foundation Center for Protein Research, Denmark) for this
      analysis. A protein-protein interaction network was further constructed using a
      tool Centralities in Biological Networks (CentiBiN) with 1020 nodes after
      eliminating the duplicates, parallel edges, self -loop edges and unknown Human
      Protein Reference Database (HPRD) IDS. We used fourteen centralities measures
      which are useful in identifying the structural characteristic of individuals in
      the network. The results of the centrality measures are highly correlated. Thus,
      we identified genes that are critically associated with DM. We further report the
      top ten genes of all fourteen centrality measures for further consideration as
      targets for DM. 

PMID- 25848170
TI  - In vitro Osteogenic impulse effect of Dexamethasone on periodontal ligament stem
      cells.
AB  - Periodontium is a complex organ composed of mineralized epithelial and connective
      tissue. Dexamethasone could stimulate proliferation of osteoblast and
      fibroblasts. This study aimed to assess the osteogenic effect of dexamethasone on
      periodental ligament (PDL) stem cells. PDL stem cells were collected from
      periodontal ligament tissue of root of extracted premolar of young and healthy
      people. The stem cells were cultured in alpha-MEM Medium in three groups, one
      group with basic medium contains (alpha- MEM and FBS 10 % and 50 mmol of beta_
      gelisrophosphat and L_ ascorbic acid ug/ml), the second group: basic medium with
      dexamethasone and the third one: basic medium without any osteogenic stimulant.
      Mineralization of cellular layer was analyzed with Alizarin red stain method.
      Osteogenic analysis was done by Alkaline phosphates and calcium test. These
      analysis indicated that the amount of intra-cellular calcium and alkaline
      phosphates in the Dexamethasone group was far more than the control and basic
      group (P<0.05). The results of Alizarin red stain indicated more mineralization
      of cultured cells in Dexamethasone group (P<0.05). The study results showed that
      Dexamethasone has significant osteogenic effect on PDL stem cells and further
      studies are recommended to evaluate its effect on treatment of bone disorders. 

PMID- 25848171
TI  - A study on the regulatory network with promoter analysis for Arabidopsis DREB
      genes.
AB  - Dehydration response element binding factors (DREBs) are one of the principal
      plant transcription factor subfamilies that regulate the expression of many
      abiotic stress-inducible genes. This sub-family belongs to AP2 transcription
      factor family and plays a considerable role in improving abiotic stresses
      tolerance in plants. Therefore, it is of interest to identify critical cis-acting
      elements involved in abiotic stress responses. In this study, we survey promoter
      cis-elements for ATDREBs genes (Arabidopsis thaliana DREBs). Regulatory networks
      based on ATDREB candidate genes were also generated to find other genes that are
      functionally similar to DREBs. The study was conducted on all 20 Arabidopsis
      thaliana non redundant DREB genes stored in RefSeq database. Promoter analysis
      and regulatory network prediction was accomplished by use of Plant CARE program
      and GeneMANIA web tool, respectively. The results indicated that among all genes,
      DREB1A, DREB1C, DREB2C, DREB2G and DEAR3 have the most type of diverse motifs
      involved in abiotic stress responses. It is implied that co-operation of abscisic
      acid, ethylene, salicylic acid and methyl jasmonate signaling is crucial for the
      regulation of the expression of drought and cold responses through DREB
      transcription factors. Gene network analysis showed different co-expressed but
      functionally similar genes that had physical and functional interactions with
      candidate DREB genes. 

PMID- 25848172
TI  - ISOB: A Database of Indigenous Snake Species of Bangladesh with respective known
      venom composition.
AB  - At present there is no well structured database available for the venomous snakes
      and venom composition of snakes in the world although venom has immense
      importance in biomedical research. Searching for a specific venom component from
      NCBI, PDB or public databases is troublesome, because they contain huge amount of
      data entries. Therefore, we created a database named "ISOB" which is a web
      accessible unique secondary database that represents the first online available
      bioinformatics resource showing venom composition of snakes. This database
      provides a comprehensive overview of seventy-eight indigenous snake species
      covering description of snakes supplemented with structural information of the
      relevant individual available venom proteins. We strongly believe that this
      database will contribute significantly in the field of bioinformatics,
      environmental research, proteomics, drug development and rationale drug
      designing. AVAILABILITY: The database is freely available at
      http://www.snakebd.com/.

PMID- 25848173
TI  - Lung resection using transumbilical incision: an animal survival study.
AB  - INTRODUCTION: Transumbilical single-port surgery is a potentially less invasive
      approach to many types of abdominal surgeries and offers better cosmetic outcomes
      than conventional 3-port laparoscopic surgery. It avoids the complication of
      intercostal neuralgia and may reduce the risk of pulmonary complications after
      video-assisted thoracic surgery. This study evaluated the feasibility of
      transumbilical lung wedge resection. METHODS: Lung resection was performed in 11
      beagle dogs weighing 5.9 to 8.5 kg. A 3-cm umbilical incision and one
      diaphragmatic incision were made, and an endoscopic stapler was used. The
      diaphragmatic incisions were repaired under video guidance using a V-Loc knotless
      suturing device (Covidien, Mansfield, Massachusetts). Animals were monitored
      daily for signs of postoperative infection. White blood cell count, C-reactive
      protein level, and IL-6 level were measured in all animals. Animals were
      euthanized 14 days after surgery and underwent necropsy evaluation. RESULTS:
      Accurate lung resection was achieved in 10 of 11 animals during a median
      operative time of 98 minutes (range 60-165). In 1 animal, transumbilical lung
      resection was not possible and was converted to thoracotomy. All animals survived
      without major postoperative complications. At necropsy, evidence of uneventful
      healing of the stapled resection margin and diaphragmatic wound were found. There
      was no evidence of vital organ injury or intrathoracic infection. CONCLUSION: A
      transumbilical approach to thoracic cavity exploration and stapled lung resection
      is technically feasible. Primary suturing of the diaphragmatic incision is a
      simple and effective means of diaphragmatic wound closure. This may be an
      alternative to video-assisted thoracic surgery for the management of simple
      thoracic disease.

PMID- 25848174
TI  - Laparoscopic adjustable gastric band: 4-year experience and learning curve.
AB  - BACKGROUND AND OBJECTIVES: Laparoscopic adjustable gastric banding has become the
      most popular procedure for the treatment of morbid obesity in Europe. The
      objectives of this series are to report the results of the 4-year experience of a
      single surgeon and to define the learning curve. METHODS: A retrospective review
      of 156 patients who underwent laparoscopic adjustable gastric banding between
      October 2006 and May 2010 was performed. Patients were separated into 3 groups:
      group 1 comprised the first 50 patients; group 2 comprised the second 50
      patients; and group 3 comprised the last group of patients, with a total of 56
      patients. RESULTS: The male-to-female ratio was 1:4 (33 male and 133 female
      patients). The mean age was 38 years (range, 17-62 years). The mean preoperative
      body mass index was 44.9 kg/m(2). The mean percent excess weight loss was 41.7%
      at the 1-year follow-up visit (153 patients, 98%), 49.7% at the 2-year follow-up
      visit (147 patients, 94%), and 50.2% at the 3-year follow-up visit (127 patients,
      81%). The overall complication rate and major complication rate were 15.4% and
      3.2%, respectively. There were no deaths. Percent excess weight loss, length of
      hospitalization (in days), and complication rates were compared among the 3
      groups. No significant differences were noted among the groups except in the
      number of complications (P < .001), but all data were clearly improved in groups
      2 and 3. CONCLUSIONS: The analyses in this study have documented one more time
      that laparoscopic adjustable gastric banding is an effective procedure for the
      treatment of morbid obesity, achieving >50% excess weight loss at 3 years. It is
      a procedure with certain complications even when performed by a surgeon with
      previous experience in laparoscopic surgery. According to our subset analysis,
      the learning curve is at least 50 procedures.

PMID- 25848175
TI  - Late results after splenectomy in adult idiopathic thrombocytopenic purpura.
AB  - BACKGROUND: We performed a retrospective study on patients with idiopathic
      thrombocytopenic purpura (ITP) to evaluate the response to splenectomy in
      relation to preoperative platelet count. MATERIALS AND METHODS: Two groups of
      patients operated on with laparoscopic or open splenectomy for ITP, with a
      platelet count <=30,000/MUL (study group: 22 patients) and >30,000/MUL (control
      group: 18 patients), respectively, were compared. The two groups were homogeneous
      in relation to age, sex, length of preoperative steroid therapy, and time
      interval between diagnosis and surgery (Student t test with P > .1). The results
      of surgery were evaluated at one year after splenectomy. Positive response to
      surgery, according to the American Society of Hematologic Guidelines, was
      considered in patients with a postoperative platelet count >=100,000/MUL or in
      patients with a postoperative platelet count >=30,000/MUL and a twofold increase
      in platelet count from baseline, in the absence of bleeding. The postoperative
      platelet count increase rate was statistically related to preoperative platelet
      count in both the study and control groups. Statistical analysis was performed
      using the Student's t test for independent sample and the Pearson correlation in
      a 2-tailed test. RESULTS: No relationship between preoperative platelet count and
      postoperative platelet percent increase was observed in the control group (r = 
      0.41; P = .089), whereas a significant negative correlation (r = -0.68; P =
      .0004) was found in the study group. CONCLUSIONS: A higher increase of
      postoperative percent platelet count may be predicted in patients with a low
      preoperative platelet count.

PMID- 25848176
TI  - Small bowel obstruction after laparoscopic gastric bypass with nonclosure of
      mesenteric defects.
AB  - BACKGROUND AND OBJECTIVES: There is a wide variation of reported incidence of
      small bowel obstruction (SBO) after laparoscopic Roux-en-Y gastric bypass (LGB).
      There is also wide variation in technique, not only in placement of the Roux
      limb, but also regarding closure or nonclosure of the mesenteric defects. The
      objective of this study was to examine the incidence and characteristics of SBO
      after antecolic antegastric bypass with nonclosure of the mesenteric defect of
      the jejunojejunal anastomosis. METHODS: This is a retrospective review of a
      series of consecutive LGBs over a 3-year period. All procedures were performed by
      the same surgeon using the same technique. In no case was the mesenteric defect
      closed. A prospectively maintained database was used for data collection.
      Patients who returned with an SBO were the study group, and those who underwent
      revisional bariatric surgery or conversion to open operation were excluded.
      RESULTS: There were 249 primary LGBs performed during the study period; 15 of the
      operations were followed by SBO, for an incidence of 6.0%. Four cases were caused
      by an internal hernia (IH), for an incidence of 1.6%, and 11 were caused by
      adhesions, which accounted for 73% of the SBOs. CONCLUSIONS: SBO after LGB is a
      relatively common complication. The incidence of SBO from IH with nonclosure of
      the mesenteric defect is similar to that in other series where the defect is
      closed. Regardless of the cause of the SBO, operative treatment of the patient
      who has a gastric bypass remains the definitive standard and should not be
      delayed.

PMID- 25848177
TI  - Early postoperative pain after keyless abdominal rope-lifting surgery.
AB  - BACKGROUND AND OBJECTIVES: Keyless abdominal rope-lifting surgery is a novel,
      gasless, single-incision laparoscopic surgical technique. In this study we aimed
      to compare the postoperative pain from keyless abdominal rope-lifting surgery
      with carbon dioxide laparoscopy performed for benign ovarian cysts. METHODS:
      During a 20-month period, 77 women underwent surgery for a benign ovarian cyst.
      Keyless abdominal rope-lifting surgery and conventional carbon dioxide
      laparoscopy techniques were used for the operations in 32 women and 45 women,
      respectively. The 2 operative techniques were compared with regard to demographic
      characteristics; preoperative, intraoperative, and postoperative data including
      early postoperative pain scores; and frequency of shoulder pain and analgesic
      requirements. RESULTS: Data regarding demographic characteristics, preoperative
      findings, cyst diameters and rupture rates, intra-abdominal adhesions,
      intraoperative blood loss, and postoperative hospital stay did not differ between
      groups (P > .05). However, the mean operative and abdominal access times were
      significantly longer in the keyless abdominal rope-lifting surgery group (P <
      .05). Visual analog scale pain scores at initially and at the second, fourth, and
      24th hours of the postoperative period were significantly lower in the keyless
      abdominal rope-lifting surgery group (P < .05). Similarly, keyless abdominal rope
      lifting surgery caused significantly less shoulder pain and additional analgesic
      use (P < .05). CONCLUSION: Keyless abdominal rope-lifting surgery seems to cause
      less pain in the management of benign ovarian cysts in comparison with
      conventional carbon dioxide laparoscopy.

PMID- 25848178
TI  - Telephone follow-up by a midlevel provider after laparoscopic inguinal hernia
      repair instead of face-to-face clinic visit.
AB  - BACKGROUND AND OBJECTIVES: The need for more cost- and time-efficient provision
      of medical care has prompted an interest in remote or telehealth approaches to
      delivery of health care. We present a study examining the feasibility and
      outcomes of implementation of a telephone follow-up program for laparoscopic
      inguinal hernia repair. METHODS: This is a retrospective review of consecutive
      patients who prospectively agreed to undergo telephone follow-up after
      laparoscopic inguinal hernia repair instead of standard face-to-face clinic
      visits. Patients received a telephone call from a dedicated physician assistant 2
      to 3 weeks after surgery and answered a predetermined questionnaire. A face-to
      face clinic visit was scheduled based on the results of the call or on patient
      request. RESULTS: Of 62 patients who underwent surgery, all agreed to telephone
      follow-up instead of face-to-face clinic visits. Their mean round-trip distance
      to the hospital was 122 miles. Fifty-five patients (88.7%) successfully completed
      planned telephone follow-up. Three patients (4.8%) were lost to follow-up, and 4
      (6.5%) were erroneously scheduled for a clinic appointment. Of the 55 patients
      who were reached by telephone, 50 (90.9%) were satisfied and declined an in
      person clinic visit. Five patients (9.1%) returned for a clinic appointment based
      on concerns raised during the telephone call. Of these, 1 was found to have an
      early hernia recurrence and 1 had a seroma. CONCLUSION: Telephone follow-up by a
      midlevel provider after laparoscopic inguinal hernia repair is feasible and
      effective and is well received by patients.

PMID- 25848179
TI  - Transient occlusion of uterine arteries in laparoscopic uterine surgery.
AB  - BACKGROUND AND OBJECTIVES: This study was conducted to determine the feasibility
      and effectiveness of transient occlusion of the uterine arteries (TOUA) during
      laparoscopic surgery for benign uterine tumors, with preservation of fertility.
      METHODS: Patients with uterine myoma or adenomyoma underwent laparoscopic uterine
      surgery, with or without TOUA, performed by a single surgeon (Y.-S.K.). Surgical
      outcomes included operative time; occurrence of intraoperative injury of blood
      vessels, nerves, and pelvic organs; and intraoperative blood loss. RESULTS: Of
      the 168 surgical patients included in this study, 144 were enrolled consecutively
      during the study period, and 24 had undergone adenomectomy before the study
      period. A total of 104 women (70 with myoma; 34 with adenomyoma) seeking uterine
      preservation underwent laparoscopic surgery with TOUA for benign uterine tumors.
      Sixty-four women (40 with myoma; 24 with adenomyoma) underwent surgery without
      TOUA. The mean total surgical time of the TOUA groups was 74.85 minutes for
      uterine myoma and 84.09 minutes for uterine adenomyoma. The mean estimated blood
      loss during laparoscopic myomectomy and adenomyomectomy was less in the TOUA
      groups than in the non-TOUA groups (109 vs. 203.4 mL in myomectomy, P < .05;
      148.1 vs. 158.9 mL in adenomyomectomy; P < .05). Time to perform TOUA was 13.9
      minutes in laparoscopic myomectomy and 7.33 minutes in laparoscopic
      adenomyomectomy. The hospital stay of the TOUA groups was 3.32 days for uterine
      myoma and 3.82 days for uterine adenomyoma. No intraoperative conversion to
      laparotomy was necessary, and no major complications occurred during any of the
      procedures. CONCLUSION: Laparoscopic uterine surgery with TOUA could be a safe
      and effective surgical method for women with symptomatic benign uterine tumors
      who wish to preserve fertility.

PMID- 25848180
TI  - Tube cholecystostomy before cholecystectomy for the treatment of acute
      cholecystitis.
AB  - BACKGROUND AND OBJECTIVES: Percutaneous cholecystostomy is currently indicated
      for patients with cholecystitis who might be poor candidates for operative
      cholecystectomy. We performed a study to evaluate the long-term outcome of
      patients undergoing emergent tube cholecystostomy. METHODS: This study was a
      retrospective chart review of patients who underwent tube cholecystostomy from
      July 1, 2005, to July 1, 2012. RESULTS: During the study period, 82 patients
      underwent 125 cholecystostomy tube placements. Four patients (5%) died during the
      year after tube placement. The mean hospital length of stay for survivors was 8.8
      days (range, 1-59 days). Twenty-eight patients (34%) required at least 1
      additional percutaneous procedure (range, 1-6) for gallbladder drainage. Twenty
      nine patients (34%) ultimately underwent cholecystectomy. Surgery was performed a
      mean of 7 weeks after cholecystostomy tube placement. Laparoscopic
      cholecystectomy was attempted in 25 operative patients but required conversion to
      an open approach in 8 cases (32%). In another 4 cases, planned open
      cholecystectomy was performed. Major postoperative complications were limited to
      2 patients with postoperative common bile duct obstruction requiring endoscopic
      retrograde cholangiopancreatography, 1 patient requiring a return to the
      operating room for hemoperitoneum, and 2 patients with bile leak from the cystic
      duct stump. CONCLUSIONS: In high-risk patients receiving cholecystostomy tubes
      for acute cholecystitis, only about one third will undergo surgical
      cholecystectomy. Laparoscopic cholecystectomy performed in this circumstance has
      a higher rate of conversion to open surgery and higher hepatobiliary morbidity
      rate.

PMID- 25848181
TI  - Laparoscopic-assisted subtotal colectomy combined with modified Duhamel procedure
      for mixed constipation.
AB  - BACKGROUND AND OBJECTIVES: To evaluate the effects of subtotal colectomy combined
      with the modified Duhamel procedure on mixed constipation. METHODS: A total of 16
      female patients with mixed constipation were enrolled and underwent subtotal
      colectomy combined with the modified Duhamel procedure under laparoscopy from
      April 2010 to April 2012. Before surgery, physical examinations such as the
      gastrointestinal transit test, barium enema, and defecography were performed for
      all the patients. After surgical treatment, 2-year follow-up was performed using
      questionnaires to assess the effect of treatment. RESULTS: All 16 cases were
      treated successfully, with a mean operation time of 230 minutes (range, 180-290
      minutes). No intraoperative or postoperative complications were found, and no
      deaths occurred. Constipation and relevant symptoms were relieved, and all
      patients were satisfied with their quality of life. The gastrointestinal quality
      of-life score was significantly increased 6 months postoperatively (mean, 102)
      compared with preoperatively (mean, 75). CONCLUSION: Subtotal colectomy combined
      with the modified Duhamel procedure under laparoscopy is effective and safe for
      the treatment of mixed constipation.

PMID- 25848182
TI  - Single-port robotic-assisted adrenalectomy: feasibility, safety, and cost
      effectiveness.
AB  - BACKGROUND AND OBJECTIVES: The introduction of robotic surgery offers patients
      and surgeons new options for adrenalectomy. Whereas multiport adrenalectomies
      have been safely performed using the robot, we describe our experience with the
      novel technique of single-port robotic-assisted adrenalectomy. METHODS: We
      performed a matched-cohort study comparing 16 single-port robotic-assisted
      adrenalectomies with 16 patients from a pool of 148 laparoscopic adrenalectomies,
      matched for age, gender, operative side, pathology, and body mass index. All were
      operated on by 1 surgeon. RESULTS: The pathology included aldosteronoma in 44% of
      patients, adrenocorticotropic hormone-dependent Cushing syndrome (bilateral
      adrenalectomy) in 19%, pheochromocytoma in 13%, and other pathology in 24%. The
      operative time was 183 +/- 33 minutes for single-port robotic-assisted
      adrenalectomy and 173 +/- 40 minutes for laparoscopic adrenalectomy (P = .58).
      The total time in the operating room was 246 +/- 33 minutes for single-port
      robotic-assisted adrenalectomy and 240 +/- 39 minutes for laparoscopic
      adrenalectomy (P = .57). There was 1 conversion to open adrenalectomy (6%) in
      each group, both because of bleeding on the right side during bilateral
      adrenalectomy. Two right-sided single-port robotic-assisted adrenalectomy
      patients required conversion to laparoscopic adrenalectomy, one because of poor
      visualization. There were no deaths. Complications occurred in 2 patients in each
      group (intensive care unit admission, prolonged ileus). Both groups had similar
      pain scores (mean of 3.7 on a scale from 1 to 10) on postoperative day 1, and
      patients in the single-port robotic-assisted adrenalectomy group used less
      narcotic pain medication in the first 24 hours after surgery (43 mg vs 84 mg in
      laparoscopic adrenalectomy group, P < .001). The differences between the single
      port robotic-assisted adrenalectomy group and laparoscopic adrenalectomy group in
      length of stay (2.3 +/- 0.5 days vs 3.1 +/- 0.9 days, P = .23), percentage of
      patients discharged on postoperative day 1 (56% vs 31%, P = .10), and hospital
      cost (16% lower in single-port robotic-assisted adrenalectomy group, P = .17) did
      not reach statistical significance. CONCLUSION: Single-port robotic adrenalectomy
      is feasible; patients require less narcotic pain medication whereas costs appear
      equivalent compared with laparoscopic adrenalectomy.

PMID- 25848183
TI  - Laparoscopic radical trachelectomy: technique, feasibility, and outcomes.
AB  - BACKGROUND AND OBJECTIVES: Our objectives are to describe our surgical technique
      for laparoscopic radical trachelectomy, to evaluate its feasibility, and to
      present the perioperative results at Hospital Italiano de Buenos Aires,
      Argentina. METHODS: We analyzed 4 patients who underwent laparoscopic radical
      trachelectomy for early-stage cervical cancer between December 2011 and May 2013.
      RESULTS: Four patients were included in this study. Total laparoscopic radical
      trachelectomy was performed in all cases. The mean age was 26 years (range, 19-32
      years), the mean body mass index was 21 (range, 18-23), and the mean length of
      hospital stay was 33 hours (range, 24-36 hours). The mean operative time was 225
      minutes (range, 210-240 minutes), and no complications were reported. During the
      postoperative period, only 1 patient presented with left vulvar edema, which
      resolved spontaneously. The pelvic and parametrial lymph nodes, as well as the
      vaginal cuff and cervical resection margins, were negative for malignancy in all
      cases. On average, 18 pelvic lymph nodes (range, 15-20) were removed. The tumor
      stage was IB in all 4 patients, and the mean tumor size was 17 mm (range, 12-31
      mm). No patient required conversion to laparotomy. CONCLUSION: We consider
      laparoscopic radical trachelectomy, performed by trained surgeons, a feasible and
      safe therapeutic option as a fertility-sparing surgical technique, with good
      perioperative outcomes for women with early-stage cervical cancer with a desire
      to preserve their fertility. Minimally invasive surgery provides the widely known
      benefits of this type of approach.

PMID- 25848184
TI  - Management of renal cysts.
AB  - BACKGROUND AND OBJECTIVES: Renal cysts have a high prevalence in the general
      population, and their estimated incidence increases with age. Renal cyst
      aspiration (usually with sclerotherapy) or open/laparoscopic decortication is a
      generally effective and safe method in the treatment of symptomatic simple renal
      cysts. The success rates of laparoscopic decortication and percutaneous
      aspiration-sclerotherapy were compared to assist in the decision making for the
      procedure. METHODS: A total of 184 patients with symptomatic simple renal cysts
      were treated with either laparoscopic decortication in 149 cases or percutaneous
      aspiration-sclerotherapy in 35 cases. The follow-up period was approximately 35
      months, and the symptomatic and radiologic success rates of the 2 techniques were
      compared retrospectively. RESULTS: Laparoscopic decortication was found to have
      high success rates, a low recurrence rate, and minimal morbidity. Percutaneous
      aspiration-sclerotherapy is an outpatient procedure with a minimally higher
      recurrence rate. CONCLUSION: When a symptomatic cyst is encountered and treatment
      of the cyst is indicated, laparoscopic decortication is a more efficient method
      that offers better results than percutaneous aspiration-sclerotherapy.

PMID- 25848185
TI  - The umbilical Benz incision for reduced port surgery in pediatric patients.
AB  - BACKGROUND AND OBJECTIVES: For reduced port surgery in pediatric patients, the
      initial umbilical incision plays an important role in both functional ability and
      cosmetic impact. Larger umbilical incisions enable better manipulation of
      forceps, extraction of larger surgical specimens, and easier exteriorization of
      the intestine for anastomosis. We have pursued an incision of the small pediatric
      umbilicus that allows for enlargement of the orifice of the abdominal opening
      with preservation of the natural umbilical profile. This article aims to present
      a new umbilical incision technique and describe the outcomes. METHODS: We devised
      a new umbilical incision technique for reduced port surgery in pediatric
      patients. Our incision is made in an inverted Y shape (Benz incision), allowing
      for access port device insertion. The Benz incision technique was applied between
      November 2010 and May 2014 and was retrospectively studied. RESULTS: Seventy-five
      patients underwent Benz incisions. The median age of all patients was 6 years 6
      months (range, 26 days to 18 years), and the median body weight was 21.7 kg
      (range, 3.1-54.3 kg). Benz incisions were applied for various procedures,
      including reduced port surgery with hepaticojejunostomy for congenital biliary
      dilatation, portojejunostomy for biliary atresia, Meckel diverticulectomy, tumor
      resection, varicocelectomy, cholecystectomy, splenectomy, ileus surgery,
      ileocecal resection, and total colectomy. All patients were successfully treated,
      without a significant increase in operating time or severe complications. The
      cosmetic profile of the umbilicus was maintained after surgery. CONCLUSION: The
      Benz incision is a feasible, effective, and scarless approach for reduced port
      surgery in pediatric patients whose umbilical rings are too small for the
      conventional approach.

PMID- 25848186
TI  - Single-port onlay mesh repair of recurrent inguinal hernias after failed anterior
      and laparoscopic repairs.
AB  - BACKGROUND AND OBJECTIVES: Despite the exponential increase in the use of
      laparoscopic inguinal herniorrhaphy, overall recurrence rates have remained
      unchanged. Therefore, a growing number of patients are presenting with recurrent
      hernias after conventional anterior and laparoscopic repairs have failed. This
      study reports our experience with single-incision laparoscopic (SIL)
      intraperitoneal onlay mesh (IPOM) repair of these hernias. METHODS: Patients
      referred with two or more recurrences of inguinal hernia underwent SIL-IPOM from
      November 1, 2009, to June 24, 2014. A 2.5-cm infraumbilical incision was made,
      and an SIL port was placed intraperitoneally. Modified dissection techniques were
      used: chopstick and inline dissection, 5.5-mm/52-cm/30 degrees  angled
      laparoscope, and conventional straight dissecting instruments. The peritoneum was
      incised above the pubic symphysis, and dissection was continued laterally and
      proximally, raising the inferior flap below the previous extraperitoneal mesh
      while reducing any direct, indirect, femoral, or cord lipoma before placement of
      antiadhesive mesh, which was fixed to the pubic ramus, as well as superiorly,
      with nonabsorbable tacks before the inferior border was fixed with fibrin
      sealant. The inferior peritoneal flap was then tacked back onto the mesh.
      RESULTS: Nine male patients underwent SIL-IPOM. Their mean age was 53 years and
      mean body mass index was 26.8 kg/m(2). Mean mesh size was 275 cm(2). Mean
      operation time was 125 minutes, with a hospital stay of 1 day. The umbilical scar
      length was 23 mm at the 6-week follow-up. There were no intra-/postoperative
      complications, port-site hernias, chronic groin pain, or recurrence of the hernia
      during a mean follow-up of 24 months. CONCLUSION: Inguinal hernias recurring
      after two or more failed conventional anterior and laparoscopic repairs can be
      safely and efficiently treated with SIL-IPOM.

PMID- 25848187
TI  - Open versus robotic radical cystectomy with intracorporeal Studer diversion.
AB  - BACKGROUND AND OBJECTIVES: To compare open versus totally intracorporeal robotic
      assisted radical cystectomy, bilateral extended pelvic lymph node dissection, and
      Studer urinary diversion in bladder cancer patients. METHODS: A retrospective
      comparison of open (n = 42) versus totally intracorporeal (n = 32) robotic
      assisted radical cystectomy, bilateral extended pelvic lymph node dissection, and
      Studer urinary diversion was performed concerning patient demographic data,
      operative and postoperative parameters, pathologic parameters, complications, and
      functional outcomes. RESULTS: Patient demographic data and the percentages of
      patients with pT2 disease or lower and pT3-pT4 disease were similar between
      groups (P > .05). Positive surgical margin rates were similar between the open (n
      = 1, 2.4%) and robotic (n = 2, 6.3%) groups (P > .05). Minor and major
      complication rates were similar between groups (P > .05). Mean estimated blood
      loss was significantly lower in the robotic group (412.5 +/- 208.3 mL vs 1314.3
      +/- 987.1 mL, P < .001). Significantly higher percentages of patients were
      detected in the robotic group regarding bilateral neurovascular bundle-sparing
      surgery (93.7% vs 64.3%, P = .004) and bilateral extended pelvic lymph node
      dissection (100% vs 71.4%, P = .001). The mean lymph node yield was significantly
      higher in the robotic group (25.4 +/- 9.7 vs 17.2 +/- 13.5, P = .005). The number
      of postoperative readmissions for minor complications was significantly lower in
      the robotic group (0 vs 7, P = .017). Better trends were detected in the robotic
      group concerning daytime continence with no pad use (84.6% vs 75%, P > .05) and
      severe daytime incontinence (8.3% vs 16.6%, P > .05). No significant differences
      were detected regarding postoperative mean International Index of Erectile
      Function scores between groups (P > .05). CONCLUSIONS: Robotic surgery has the
      advantages of decreased blood loss, better preservation of neurovascular bundles,
      an increased lymph node yield, a decreased rate of hospital readmissions for
      minor complications, and a better trend for improved daytime continence when
      compared with the open approach.

PMID- 25848188
TI  - Procedural changes to decrease complications in laparoscopic gastric bypass.
AB  - BACKGROUND AND OBJECTIVES: Laparoscopic Roux-en-Y gastric bypass (LRYGB) is a
      complex procedure performed in a patient population with significant medical
      comorbidities. Evaluation and modification of surgical techniques can minimize
      the complications associated with the lengthy learning curve for this procedure.
      The purpose of this study was to evaluate a single surgeon's decade-long
      experience with LRYGB, to determine whether complications decreased with
      experience and surgical modifications improved perioperative outcomes. METHODS: A
      retrospective review of all procedures performed by a fellowship-trained surgeon
      (MK) from December 1, 2000, to October 31, 2013, identified patients who
      underwent LRYGB. We evaluated perioperative outcomes in 1117 patients and
      examined the impact of modification of surgical techniques on complications. The
      patients were divided into 4 groups: cases 1-100 (group 1), cases 101-400 (group
      2), cases 401-700 (group 3), and cases 701-1117 (group 4). RESULTS: Operating
      time decreased significantly after the initial 100 cases, from 179.1 minutes for
      group 1 to 122.1 minutes for group 4. With experience, early complication rates
      improved from 25.0% to 5.0%, but the rates of early reoperation increased from
      1.0% to 2.2% over the 4 case groups. Late complication and reoperation rates
      increased from 4.0% to 10.5%. However, rates of bleeding, early stricture,
      internal hernia, and wound infection all decreased after the modification of
      surgical techniques. CONCLUSIONS: Operating time and early complication rates
      decreased with operative experience, but late complication and early and late
      reoperation rates increased. However, after modifications of surgical technique,
      common complications of LRYGB decreased to rates lower than those reported in
      several gastric bypass case series in the literature. The findings in this study
      will be helpful to fellow bariatric surgeons who are refining their strategies
      for reducing morbidity related to LRGYB.

PMID- 25848189
TI  - Minimally invasive specialists and rates of laparoscopic hysterectomy.
AB  - BACKGROUND AND OBJECTIVE: Despite the prevalence of hysterectomy for treatment of
      benign gynecologic conditions, providers nationwide have been slow to adopt
      minimally-invasive surgical techniques. Our objective is to investigate the
      impact of a department for minimally invasive gynecologic surgery (MIGS) on the
      rate of laparoscopic hysterectomy at an academic community hospital without
      robotic technology. METHODS: This retrospective observational study included all
      patients who underwent hysterectomy for benign indications from January 1, 2004,
      through December 31, 2012. The primary outcome was route of hysterectomy: open,
      laparoscopic, or vaginal. Secondary outcomes of interest included length of stay
      and factors associated with an open procedure. RESULTS: In 2004, only 24 (8%) of
      the 292 hysterectomies performed for benign conditions at Newton-Wellesley
      Hospital (NWH) were laparoscopic. The rate increased to more than 50% (189/365)
      by 2008, and, in 2012, 72% (316/439) of hysterectomies were performed via a
      traditional laparoscopic approach. By 2012, more than 93% (411/439) of all
      hysterectomies were performed in a minimally invasive manner (including total
      laparoscopic hysterectomy [TLH], laparoscopic supracervical hysterectomy [LSH],
      total vaginal hysterectomy [TVH], and laparoscopy-assisted vaginal hysterectomy
      [LAVH]). More than 85% of the hysterectomies at NWH in 2012 were outpatient
      procedures. By this time, the surgeon's preference or lack of expertise was
      rarely cited as a factor leading to open hysterectomy. CONCLUSIONS: A large
      diverse gynecologic surgery department transformed surgical practice from
      primarily open hysterectomy to a majority (>72%) performed via the traditional
      laparoscopic route and a large majority (>93%) performed in a minimally invasive
      manner in less than 8 years, without the use of robotic technology. This paradigm
      shift was fueled by patient demand and by MIGS department surgical mentorship for
      generalist obstetrician/gynecologists.

PMID- 25848190
TI  - Competence acquisition for single-incision laparoscopic cholecystectomy.
AB  - BACKGROUND AND OBJECTIVES: Within the past few years, there has been a push for
      an even more minimally invasive approach to biliary disease with the adoption of
      single-incision laparoscopic cholecystectomy. We sought to compare 4 individual
      surgeon experiences to define whether there exists a learning curve for
      performing single-incision laparoscopic cholecystectomy. METHODS: We performed a
      retrospective review 290 single-incision laparoscopic cholecystectomies performed
      by a group of general surgeons, with varying levels of experience and training,
      at 3 institutions between May 2008 and September 2010. The procedure times were
      recorded for each single-incision laparoscopic cholecystectomy, ordered
      chronologically for each surgeon, and subsequently plotted on a graph. The
      patients were also combined into cohorts of 5 and 10 cases to further evaluate
      for signs of improvement in operative efficiency. RESULTS: Of the 4 surgeons
      involved in the study, only 1 (surgeon 4, laparoscopic fellowship trained with <5
      years' experience) confirmed the presence of a learning curve, reaching
      proficiency within the first 15 cases performed. The other surgeons had more
      variable procedure times, which did not show a distinct trend. When we evaluated
      the cases by cohorts of 5 cases, surgeon 4 had a significant difference between
      the first and last cohort. Increased body mass index resulted in a slightly
      longer operative time (P < .0063). The conversion rate to multiport laparoscopic
      surgery was 3.1%. CONCLUSIONS: Our results indicate that among experienced
      general surgeons, there does not seem to be a significant learning curve when
      transitioning from conventional laparoscopic cholecystectomy to single-incision
      laparoscopic cholecystectomy. The least experienced surgeon in the group, surgeon
      4, appeared to reach proficiency after 15 cases. Greater than 5 years of
      experience in laparoscopic surgery appears to provide surgeons with a sufficient
      skill set to obviate the need for a single-incision laparoscopic cholecystectomy
      learning curve.

PMID- 25848191
TI  - The safety and efficacy of approaches to liver resection: a meta-analysis.
AB  - BACKGROUND: The aim of this study is to compare the safety and efficacy of
      conventional laparotomy with those of robotic and laparoscopic approaches to
      hepatectomy. DATABASE: Independent reviewers conducted a systematic review of
      publications in PubMed and Embase, with searches limited to comparative articles
      of laparoscopic hepatectomy with either conventional or robotic liver approaches.
      Outcomes included total operative time, estimated blood loss, length of
      hospitalization, resection margins, postoperative complications, perioperative
      mortality rates, and cost measures. Outcome comparisons were calculated using
      random-effects models to pool estimates of mean net differences or of the
      relative risk between group outcomes. Forty-nine articles, representing 3702
      patients, comprise this analysis: 1901 (51.35%) underwent a laparoscopic
      approach, 1741 (47.03%) underwent an open approach, and 60 (1.62%) underwent a
      robotic approach. There was no difference in total operative times, surgical
      margins, or perioperative mortality rates among groups. Across all outcome
      measures, laparoscopic and robotic approaches showed no difference. As compared
      with the minimally invasive groups, patients undergoing laparotomy had a greater
      estimated blood loss (pooled mean net change, 152.0 mL; 95% confidence interval,
      103.3-200.8 mL), a longer length of hospital stay (pooled mean difference, 2.22
      days; 95% confidence interval, 1.78-2.66 days), and a higher total complication
      rate (odds ratio, 0.5; 95% confidence interval, 0.42-0.57). CONCLUSION: Minimally
      invasive approaches to liver resection are as safe as conventional laparotomy,
      affording less estimated blood loss, shorter lengths of hospitalization, lower
      perioperative complication rates, and equitable oncologic integrity and
      postoperative mortality rates. There was no proven advantage of robotic
      approaches compared with laparoscopic approaches.

PMID- 25848192
TI  - Distal pancreatectomy and splenectomy: a robotic or LESS approach.
AB  - INTRODUCTION: The role and application of robotic surgery are debated,
      particularly given the expansion of laparoscopy, especially laparoendoscopic
      single-site (LESS) surgery. This cohort study was undertaken to delineate
      differences in outcomes between LESS and robotic distal pancreatectomy and
      splenectomy. METHODS: With Institutional Review Board approval, patients
      undergoing LESS or robotic distal pancreatectomy and splenectomy from September
      1, 2012, through December 31, 2014, were prospectively observed, and data were
      collected. The results are expressed as the median, with the mean +/- SD.
      RESULTS: Thirty-four patients underwent a minimally invasive distal
      pancreatectomy and splenectomy: 18 with robotic and 16 with LESS surgery. The
      patients were similar in sex, age, and body mass index. Conversions to open
      surgery and estimated blood loss were similar. There were two intraoperative
      complications in the group that underwent the robotic approach. Time spent in the
      operating room was significantly longer with the robot (297 vs 254 minutes, P =
      .03), although operative duration (i.e., incision to closure) was not longer (225
      vs 190 minutes; P = .15). Of the operations studied, 79% were undertaken for
      neoplastic processes. Tumor size was 3.5 cm for both approaches; R0 resections
      were achieved in all patients. Length of stay was similar in the two study groups
      (5 vs 4 days). There was one 30-day readmission after robotic surgery.
      CONCLUSIONS: Patient outcomes are similar with LESS or robotic distal
      pancreatectomy and splenectomy. Robotic operations require more time in the
      operating room. Both are safe and efficacious minimally invasive operations that
      follow similar oncologic principles for similar tumors, and both should be in the
      surgeon's armamentarium for distal pancreatectomy and splenectomy.

PMID- 25848193
TI  - Laparoscopic transcystic choledochotomy with primary suture for choledocholith.
AB  - BACKGROUND AND OBJECTIVES: To investigate the possibility of extracting common
      bile duct (CBD) stones by laparoscopically inserting choledochoscope through the
      natural orifice of the cystic duct and a mini-incision on the CBD, and the safety
      of laparoscopic primary double-layer suture of the cystic duct and CBD. METHODS:
      Laparoscopic transcystic choledochotomy and extraction of stones with primary
      suture was performed on 194 patients with gallbladder and CBD stones from October
      1, 2009, through April 30, 2012. The cystic duct was left at a diameter of 1 to
      1.5 cm after removal of the gallbladder. The duct was longitudinally cut at its
      ventral side to the confluence with the CBD, and the anterior wall of the CBD was
      also cut longitudinally. A choledochoscope was then inserted via the enlarged
      opening, and the stones were extracted from the CBD. Finally, the CBD and cystic
      duct were closed by continuous mucous layer suture and seromuscular Lembert
      suture, respectively. The cystic duct was ligated close to the CBD and an
      abdominal drainage tube was placed. RESULTS: All surgical procedures were
      successfully performed. The caliber at the confluence between the cystic duct and
      the CBD was 0.3 to 0.8 cm (SD 0.4 +/- 0.1 cm), and the mini-incision of the CBD
      was 0.1 to 1.1 cm (SD 0.3 +/- 0.2 cm). Abdominal drainage lasted 3 to 5 days.
      Magnetic resonance cholangiopancreatography (MRCP) in 55 patients showed no
      abnormal change in the CBD diameter. Two patients had bile leakage. Another
      patient had intermittent abdominal pain and jaundice 5 to 7 days postoperatively,
      and the retained stones spontaneously passed. The postoperative hospital stay was
      6 to 13 days (SD 8 +/- 2.1 days). Observation of 176 patients (90%) lasting 1 to
      30 months (SD 11 +/- 8 months) showed no recurrent stones or stricture of the
      CBD. CONCLUSION: The surgical procedure of laparoscopic transcystic
      choledochotomy and extraction of stones with primary suture is feasible and safe.

PMID- 25848194
TI  - Sonohysterographic predictors of successful hysteroscopic myomectomies.
AB  - BACKGROUND AND OBJECTIVES: The purpose of this study is to assess the rate of
      persistent submucosal myomas and intrauterine scarring after hysteroscopic
      myomectomy, as well as to evaluate the preoperative and intraoperative
      sonohysterographic findings that will predict persistence of myomas, scarring,
      and the need for repeat surgery. METHODS: Charts from all hysteroscopic
      myomectomies performed by a single surgeon between 2003 and 2011 were reviewed
      for preoperative, intraoperative, and postoperative sonohysterographic findings.
      Predictors included myoma number, diameter and percent extension into the cavity
      of the largest fibroid, and percent surgically resected. These predictors were
      assessed with postoperative sonohysterography. Statistics included t test,
      logistic regression, chi(2) test, and Fisher exact test. RESULTS: Among the 79
      cases with postoperative sonohysterograms, 17 (21.5%) had persistent submucosal
      myoma, and 9 (11.4%) had intrauterine scarring on postoperative sonohysterogram.
      Repeat hysteroscopic myomectomy was required in 11 (13.9%), but none required
      lysis of adhesions. The myoma number was not a significant predictor. A higher
      percentage of myoma within the cavity (63.35% vs 44.89%, P < .05) and smaller
      myoma size (2.22 cm vs 3.31 cm, P < .01) were significant predictors of a
      complete resection, a normal postoperative sonohysterogram, and avoidance of
      repeat surgery. On regression analysis, the percent of the myoma resected was the
      most significant outcome predictor (P < .001). CONCLUSION: Larger myomas with a
      lower percent found within the uterine cavity are less likely to be completely
      resected. Percent resection at the time of surgery is the most significant
      predictor of a normal postoperative sonohysterogram, as well as the best
      predictor of the need for repeat surgery.

PMID- 25848195
TI  - Magnetic resonance-visible meshes for laparoscopic ventral hernia repair.
AB  - BACKGROUND AND OBJECTIVES: We aimed to evaluate the first human use of magnetic
      resonance-visible implants for intraperitoneal onlay repair of incisional hernias
      regarding magnetic resonance presentability. METHODS: Ten patients were
      surgically treated with intraperitoneally positioned superparamagnetic flat
      meshes. A magnetic resonance investigation with a qualified protocol was
      performed on postoperative day 1 and at 3 months postoperatively to assess mesh
      appearance and demarcation. The total magnetic resonance-visible mesh surface
      area of each implant was calculated and compared with the original physical mesh
      size to evaluate potential reduction of the functional mesh surfaces. RESULTS: We
      were able to show a precise mesh demarcation, as well as accurate assessment of
      the surrounding tissue, in all 10 cases. We documented a significant decrease in
      the magnetic resonance-visualized total mesh surface area after release of the
      pneumoperitoneum compared with the original mesh size (mean, 190 cm(2) vs 225
      cm(2); mean reduction of mesh area, 35 cm(2); P < .001). At 3 months
      postoperatively, a further reduction of the surface area due to significant mesh
      shrinkage could be observed (mean, 182 cm(2) vs 190 cm(2); mean reduction of mesh
      area, 8 cm(2); P < .001). CONCLUSION: The new method of combining magnetic
      resonance imaging and meshes that provide enhanced signal capacity through direct
      integration of iron particles into the polyvinylidene fluoride base material
      allows for detailed mesh depiction and quantification of structural changes. In
      addition to a significant early postoperative decrease in effective mesh surface
      area, a further considerable reduction in size occurred within 3 months after
      implantation.

PMID- 25848196
TI  - A comparison of open surgery, robotic-assisted surgery and conventional
      laparoscopic surgery in the treatment of morbidly obese endometrial cancer
      patients.
AB  - BACKGROUND AND OBJECTIVES: The intent of this retrospective study was to assess
      the operative outcomes of morbidly obese endometrial cancer patients who were
      treated with either open surgery (OS) or a minimally invasive procedure. METHODS:
      Morbidly obese (body mass index [BMI] > 40 kg/m(2)) patients with endometrial
      cancer who underwent OS, robotic-assisted laparoscopic surgery (RS), or
      conventional laparoscopic surgery (LS) were eligible. We sought to discern any
      outcome differences with regard to operative time, perioperative complications,
      and hospital stay. RESULTS: Sixteen patients were treated with LS (BMI = 47.9
      kg/m(2)), 13 were managed via RS (BMI = 51.2 kg/m(2)), and 24 underwent OS (BMI =
      53.7 kg/m(2)). The OS (1.35 hours) patients had a significantly shorter operative
      duration than the LS (1.82 hours) and RS (2.78 hours) patients (P < .001); blood
      loss was greater in the OS (250 mL) group in comparison with the RS (100 mL) and
      LS (175 mL) patients (P = .002). Moreover, the OS (4 days) subjects had a
      significantly longer hospital stay than the LS (2 days) and RS (2 days) patients
      (P = .002). CONCLUSION: In the present study, we ascertained that minimally
      invasive surgery was associated with longer operative times but lower rates of
      blood loss and shorter hospital stay duration compared with treatment comprising
      an open procedure.

PMID- 25848197
TI  - Histopathologic findings in the resected specimen of a sleeve gastrectomy.
AB  - BACKGROUND AND OBJECTIVES: The vertical sleeve gastrectomy is quickly becoming a
      preferred bariatric operation. There is a dearth of published data about
      histopathologic changes in the specimens of morbidly obese patients, especially
      sleeve patients. The aim of this study is to add more data about the
      characteristics of the resected gastric specimens to the published literature.
      METHODS: A prospective database of all patients undergoing laparoscopic sleeve
      gastrectomies at a single institution was used to gather our data. Patient
      characteristics such as age, sex, and initial body mass index were examined. The
      pathology reports of these patients were examined for any histopathologic changes
      or findings. RESULTS: One hundred forty-five patients over a 3-year period had
      specimens available for review. Ninety-seven of the patients were women. The mean
      starting body mass index was 47.5 kg/m(2) (range, 35-72.8 kg/m(2)). The mean age
      at the time of the operation was 43.1 years. A minority of patients, 62 (49.7%),
      had histopathologic findings in the resected specimens. The main histopathologic
      findings were acute and chronic gastritis in 4 patients, chronic gastritis in 61,
      and follicular lymphoid hyperplasia in 11. One leiomyoma and 2 fundic polyps were
      found. Seventy-three patients had no histopathologic changes. CONCLUSION: A
      minority of patients had pathologic findings in the resected specimens. This
      study will help build a dataset regarding the resected stomachs of morbidly obese
      individuals. These results can help determine what histopathologic findings can
      be expected after sleeve gastrectomies.

PMID- 25848199
TI  - Erratum.

PMID- 25848198
TI  - Endoscopic gastrostomy button with double-lasso U-stitch in children.
AB  - BACKGROUND AND OBJECTIVES: Placement of surgical gastric access is a common
      operative procedure, with multiple techniques. We describe a cost-effective,
      safe, and easy-to-perform primary endoscopic gastrostomy button placement in the
      pediatric population, using a novel double-transcutaneous lasso U-stitch push
      technique. METHODS: This is a retrospective review of a single center's
      experience of 24 consecutively performed primary gastrostomy button placements in
      infants and children aged 3 weeks to 20 years, from October 2012 through October
      2014. RESULTS: The procedure was generally well tolerated, with no intraoperative
      complications. No conversions to laparoscopic or open procedures were necessary.
      There were no early tube dislodgements and no postoperative complications within
      the first 4 weeks. CONCLUSION: The endoscopic primary gastrostomy button
      placement with a transcutaneous lasso U-stitch is a safe, fast, elegant, and cost
      effective alternative to a standard percutaneous endoscopic gastrostomy
      placement.

PMID- 25848200
TI  - Stenting for obstructing colon cancer: fewer complications and colostomies.
AB  - BACKGROUND AND OBJECTIVES: Colonic stenting has been used in the setting of
      malignant obstruction to avoid an emergent colectomy. We sought to determine
      whether preoperative placement of a colonic stent decreases morbidity and the
      rate of colostomy formation. METHODS: Cases of obstructing sigmoid, rectosigmoid,
      and rectal cancer from January 1, 2010, to December 31, 2011, were identified in
      the Nationwide Inpatient Sample (NIS) database. All patients were treated at
      hospitals in the United States, and the database generated national estimates.
      Postoperative complications, mortality, and the rate of colostomy formation were
      analyzed. RESULTS: Of the estimated 7891 patients who presented with obstructing
      sigmoid, rectosigmoid, or rectal cancer necessitating intervention, 12.1% (n =
      956) underwent placement of a colonic stent, and the remainder underwent surgery
      without stent placement. Of the patients who underwent stenting, 19.9% went on to
      have colon resection or stoma creation during the same admission. Patients who
      underwent preoperative colonic stent placement had a lower rate of total
      postoperative complications (10.5% vs 21.7%; P < .01). There was no significant
      difference in mortality (4.7% vs 4.2%; P = .69). The rate of colostomy formation
      was more than 2-fold higher in patients who did not undergo preoperative stenting
      (42.5% vs 19.5%; P < .01). Preoperative stenting was associated with increased
      use of laparoscopy (32.6% vs 9.7%; P < .01). CONCLUSIONS: Our study characterizes
      the national incidence of preoperative placement of a colonic stent in the
      setting of malignant obstruction. Preoperative stent placement is associated with
      lower postoperative complications and a lower rate of colostomy formation. The
      results support the hypothesis that stenting as a bridge to surgery may benefit
      patients by converting an emergent surgery into an elective one.

PMID- 25848201
TI  - Text (Oral) Reading Fluency as a Construct in Reading Development: An
      Investigation of its Mediating Role for Children from Grades 1 to 4.
AB  - In the present study we investigated a developmentally changing role of text
      reading fluency in mediating the relations of word reading fluency and listening
      comprehension to reading comprehension. We addressed this question by using
      longitudinal data from Grades 1 to 4, and employing structural equation models.
      Results showed that the role of text reading fluency changes over time as
      children's reading proficiency develops. In the beginning phase of reading
      development (Grade 1), text reading fluency was not independently related to
      reading comprehension over and above word reading fluency and listening
      comprehension. In Grades 2 to 4, however, text reading fluency completely
      mediated the relation between word reading fluency and reading comprehension
      whereas it partially mediated the relation between listening comprehension and
      reading comprehension. These results suggest that text reading fluency is a
      dissociable construct that plays a developmentally changing role in reading
      acquisition.

PMID- 25848202
TI  - Optomap ultrawide field imaging identifies additional retinal abnormalities in
      patients with diabetic retinopathy.
AB  - PURPOSE: To compare diabetic retinopathy (DR) severity grading between Optomap
      ultrawide field scanning laser ophthalmoscope (UWFSLO) 200 degrees  images and an
      Early Treatment Diabetic Retinopathy Study (ETDRS) seven-standard field view.
      METHODS: Optomap UWFSLO images (total: 266) were retrospectively selected for
      evidence of DR from a database of eye clinic attendees. The Optomap UWFSLO images
      were graded for DR severity by two masked assessors. An ETDRS seven-field mask
      was overlaid on the Optomap UWFSLO images, and the DR grade was assessed for the
      region inside the mask. Any interassessor discrepancies were adjudicated by a
      senior retinal specialist. Kappa agreement levels were used for statistical
      analysis. RESULTS: Fifty images (19%) (P<0.001) were assigned a higher DR level
      in the Optomap UWFSLO view compared to the ETDRS seven-field view, which resulted
      in 40 images (15%) (P<0.001) receiving a higher DR severity grade. DR severity
      grades in the ETDRS seven-field view compared with the Optomap UWFSLO view were
      identical in 85% (226) of the images and within one severity level in 100% (266)
      of the images. Agreement between the two views was substantial: unweighted kappa
      was 0.74+/-0.04 (95% confidence interval: 0.67-0.81) and weighted kappa was
      0.80+/-0.03 (95% confidence interval: 0.74-0.86). CONCLUSION: Compared to the
      ETDRS seven-field view, a significant minority of patients are diagnosed with
      more severe DR when using the Optomap UWFSLO view. The clinical significance of
      additional peripheral lesions requires evaluation in future prospective studies
      using large cohorts.

PMID- 25848203
TI  - Current perspectives on ranibizumab.
AB  - BACKGROUND: This review summarizes the Phase III studies addressing intravitreal
      ranibizumab treatment in patients with neovascular age-related macular
      degeneration (AMD), macular edema (ME) from retinal vein occlusion (RVO), and
      diabetic ME (DME). RESULTS: The data from 12 major Phase III studies: six studies
      in patients with neovascular AMD, two studies in patients with ME from RVO, and
      four studies in patients with DME demonstrate significant improvement in vision
      in patients undergoing treatment with intravitreal ranibizumab over patients
      receiving no treatment or receiving only grid laser. These effects are achieved
      with low incidences of ocular and nonocular adverse events. CONCLUSION:
      Intravitreal ranibizumab is a highly effective and safe therapy for improving
      vision and reducing vision loss in patients with neovascular AMD, ME from RVO,
      and DME. Patients generally require long-term treatment although some data show
      that frequency of treatment necessary to maintain visual outcomes decreases over
      time.

PMID- 25848204
TI  - Measurement of serum and vitreous concentrations of anti-type II collagen
      antibody in diabetic retinopathy.
AB  - BACKGROUND: Autoimmune mechanisms have been postulated as a cause of diabetic
      retinopathy (DR), as several autoantibodies have reportedly been detected in the
      serum of DR patients. In this present study, we measured serum and vitreous
      levels of anti-type II collagen (anti-II-C) antibodies in DR patients and
      investigated their association with the mechanism of development of DR. PATIENTS
      AND METHODS: Blood samples were obtained from patients with proliferative DR and
      from patients with diabetic macular edema who underwent vitrectomy at Osaka
      Medical College, Takatsuki City, Osaka, Japan. Diabetic patients without DR were
      also included. The control group consisted of age- and sex-matched patients with
      noninflammatory eye diseases who underwent eye surgery for retinal detachment or
      for cataracts. The levels of anti-II-C immunoglobulin (Ig)G antibody in the
      vitreous and serum were measured using a human/monkey anti-II-C IgG assay kit.
      RESULTS: The serum levels of anti-II-C IgG antibody were significantly higher in
      the DR patients than in the patients with noninflammatory eye disease (56.8+/
      33.8 units/mL versus 30.5+/-13.7 units/mL, respectively; P<0.05, Fisher's exact
      test). These levels were also significantly higher in the diabetic patients
      without DR than in the patients with noninflammatory eye disease (76.3+/-49.7
      units/mL versus 30.5+/-13.7 units/mL, respectively; P<0.01, Fisher's exact test).
      However, anti-II-C IgG antibody levels were unable to be detected in all of the
      obtained vitreous fluid samples. CONCLUSION: The development and progression of
      DR may be related to a mechanism involving intraocular type II collagen, which
      normally has immunological tolerance as a sequestered antigen. In DR, the
      disruption of the blood-retinal barrier leads to contact between the intraocular
      type II collagen and immunocompetent cells, and to subsequent activation of the
      autoimmune mechanism.

PMID- 25848205
TI  - Vitreous estrogen levels in patients with an idiopathic macular hole.
AB  - PURPOSE: Estrogen, a female hormone, activates collagenase and might be
      associated with the pathogenesis of vitreoretinal collagen fiber disease. The
      purpose of the present study was to investigate the vitreous levels of estrone
      (E1) and estradiol (E2) in subjects with an idiopathic macular hole (IMH).
      METHODS: Vitreous samples were obtained from ten female patients with an IMH and
      from nine female patients with other retinal diseases (six with rhegmatogenous
      retinal detachment and three with age-related macular degeneration) as a control
      at the time of vitreous surgery. E1 and E2 levels in the vitreous samples were
      then determined using the Coat-A-Count((r)) Estradiol Radioimmunoassay (RIA) Kit
      and the DSL-70 Estrone RIA Kit, respectively. RESULTS: The mean vitreous levels
      of E1 and E2 in the subjects with IMH were 1.83+/-2.00 pg/mL and 7.03+/-2.97
      pg/mL, respectively, whereas in the control subjects they were 2.42+/-1.25 pg/mL
      and 4.90+/-2.90 pg/mL, respectively. Thus, the vitreous E2 levels in the subjects
      with IMH were significantly higher than in the controls (P<0.05). CONCLUSION: The
      findings of this study suggest that E2 might be associated with the pathogenesis
      of IMH, but further investigation is needed to elucidate that association.

PMID- 25848206
TI  - Unilateral rhino-orbital-cerebral mucormycosis with contralateral endogenous
      fungal endophthalmitis.
AB  - Rhino-orbital-cerebral mucormycosis (ROCM) is an uncommon but fatal fungal
      infection. We report a rare case of unilateral ROCM with ipsilateral central
      retinal artery occlusion and contralateral choroiditis, which later progressed to
      endogenous fungal endophthalmitis. The patient was successfully treated with
      sinuses debridement, systemic liposomal amphotericin B, and intravitreal
      amphotericin B. The endophthalmitis completely resolved with good vision, but the
      ROCM eye remained blind due to central retinal artery occlusion. 

PMID- 25848207
TI  - The effect of Nd:YAG laser treatment of posterior capsule opacification on
      anterior chamber depth and refraction in pseudophakic eyes.
AB  - PURPOSE: This was a prospective descriptive study to determine the changes in
      intraocular lens (IOL) position after neodymium-doped yttrium-aluminum-garnet
      (Nd:YAG) laser posterior capsulotomy by measuring anterior chamber depth (ACD)
      and refraction, including the spherical equivalent (SE) and cylinder. MATERIALS
      AND METHODS: Forty-seven pseudophakic eyes with posterior capsule opacification
      of 29 patients were included. Nd:YAG laser posterior capsulotomy was performed.
      Patients' ACD and refraction were measured before the treatment, as well as after
      the treatment at 1 week and 3 months. IOLMaster((r)) and an automated
      refractometer were used at the Department of Ophthalmology, King Chulalongkorn
      Memorial Hospital, Bangkok, Thailand. RESULTS: There were no statistically
      significant differences in ACD and SE before and after laser treatment at 1 week
      and 3 months (repeated analysis of variance, P=0.582 and P=0.269, respectively).
      Both backward IOL movement (number [n]=29) and forward IOL movement (n=18) were
      found. Some changes in cylindrical refraction were found at 1 week, but decreased
      at 3 months after capsulotomy (baseline cylinder: -1.16; cylinder at 1 week and 3
      months: -1.00 and -1.14, respectively; P=0.012). These changes were the same with
      one-piece and three-piece IOLs. CONCLUSION: Nd:YAG laser posterior capsulotomy
      did not significantly change ACD and SE. It led to cylinder change at 1 week
      after laser, but the effect decreased at 3 months. This effect was small and may
      not be clinically significant.

PMID- 25848208
TI  - Glu-Trp-ONa or its acylated analogue (R-Glu-Trp-ONa) administration enhances the
      wound healing in the model of chronic skin wounds in rabbits.
AB  - The management of chronic skin wounds represents a major therapeutic challenge.
      The synthesized dipeptide (Glu-Trp-ONa) and its acylated analogue (R-Glu-Trp-ONa)
      were assessed in the model of nonhealing dermal wounds in rabbits in relation to
      their healing properties in wound closure. Following wound modeling, the rabbits
      received a course of intraperitoneal injections of Glu-Trp-ONa or R-Glu-Trp-ONa.
      Phosphate-buffered saline and Solcoseryl(r) were applied as negative and positive
      control agents, respectively. An injection of Glu-Trp-ONa and R-Glu-Trp-ONa
      decreased the period of wound healing in animals in comparison to the control and
      Solcoseryl-treated groups. Acylation of Glu-Trp-ONa proved to be beneficial as
      related to the healing properties of the dipeptide. Subsequent zymography
      analyses showed that the applied peptides decreased the proteolytic activity of
      matrix metalloproteinases MMP-9, MMP-8, and MMP-2 in the early inflammatory phase
      and reversely increased the activity of MMP-9, MMP-8, and MMP-1 in the remodeling
      phase. Histological analyses of the wound sections (hematoxylin-eosin, Mallory's
      staining) confirmed the enhanced formation of granulation tissue and re
      epithelialization in the experimental groups. By administering the peptides,
      wound closures increased significantly through the modulation of the MMPs'
      activity, indicating their role in wound healing.

PMID- 25848209
TI  - Brentuximab vedotin for relapsed or refractory Hodgkin's lymphoma.
AB  - Brentuximab vedotin is a promising antibody-drug conjugate (ADC) targeting CD30
      of tumor cells. It selectively delivers monomethyl auristatin E (MMAE) into CD30
      expressing cells and induces tumor cell apoptosis. Various clinical trials have
      provided evidence that it is effective in relapsed or refractory Hodgkin's
      lymphoma (HL), and it has also shown its advantages in other CD30-positive
      lymphomas. In this review, we focus on the structure, mechanisms, and
      pharmacokinetics of brentuximab vedotin. We also summarize clinical trials with
      brentuximab vedotin and make recommendations for brentuximab vedotin in the
      treatment of relapsed or refractory HL.

PMID- 25848210
TI  - Single and multiple dose pharmacokinetics and tolerability of HX-1171, a novel
      antioxidant, in healthy volunteers.
AB  - BACKGROUND: HX-1171 (1-O-hexyl-2,3,5-trimethylhydroquinone) is a promising
      antioxidant with therapeutic potential for hepatic fibrosis. The aim of this
      study was to investigate the tolerability and pharmacokinetics of HX-1171 in
      healthy volunteers. METHODS: A randomized, single-blind, placebo-controlled, dose
      escalation study was conducted in 83 subjects. In the single ascending dose
      study, 20, 40, 80, 160, 300, 600, 1,200, 1,500 or 2,000 mg of HX-1171 was
      administered to 67 subjects. In the multiple ascending dose study, 500 or 1,000
      mg was administered to 16 subjects for 14 days. The plasma and urine
      concentrations of HX-1171 were determined by using a validated liquid
      chromatography-mass spectrometry method. Pharmacokinetic parameters were obtained
      by non-compartmental analysis. Tolerability was assessed based on physical
      examinations, vital signs, clinical laboratory tests, and electrocardiograms.
      RESULTS: Adverse events reported in the study were all mild in intensity and
      resolved without any sequelae. HX-1171 was rapidly and minimally absorbed with a
      median time at maximal concentration of 0.63-1.50 hours and slowly eliminated
      with a terminal half-life of 21.12-40.96 hours. Accumulation index ranged from
      2.0 to 2.2 after repeated dosing for 14 days. For both the single and multiple
      doses administrations, urinary concentrations indicated that less than 0.01% of
      the HX-1171 administered was excreted in urine. CONCLUSION: HX-1171 was well
      tolerated and minimally absorbed in healthy volunteers. The pharmacokinetic
      profile of HX-1171 was consistent with once-a-day dosing.

PMID- 25848211
TI  - Design and prediction of new anticoagulants as a selective Factor IXa inhibitor
      via three-dimensional quantitative structure-property relationships of
      amidinobenzothiophene derivatives.
AB  - Factor IXa (FIXa), a blood coagulation factor, is specifically inhibited at the
      initiation stage of the coagulation cascade, promising an excellent approach for
      developing selective and safe anticoagulants. Eighty-four amidinobenzothiophene
      antithrombotic derivatives targeting FIXa were selected to establish three
      dimensional quantitative structure-activity relationship (3D-QSAR) and three
      dimensional quantitative structure-selectivity relationship (3D-QSSR) models
      using comparative molecular field analysis and comparative similarity indices
      analysis methods. Internal and external cross-validation techniques were
      investigated as well as region focusing and bootstrapping. The satisfactory q (2)
      values of 0.753 and 0.770, and r (2) values of 0.940 and 0.965 for 3D-QSAR and 3D
      QSSR, respectively, indicated that the models are available to predict both the
      inhibitory activity and selectivity on FIXa against Factor Xa, the activated
      status of Factor X. This work revealed that the steric, hydrophobic, and H-bond
      factors should appropriately be taken into account in future rational design,
      especially the modifications at the 2'-position of the benzene and the 6-position
      of the benzothiophene in the R group, providing helpful clues to design more
      active and selective FIXa inhibitors for the treatment of thrombosis. On the
      basis of the three-dimensional quantitative structure-property relationships, 16
      new potent molecules have been designed and are predicted to be more active and
      selective than Compound 33, which has the best activity as reported in the
      literature.

PMID- 25848212
TI  - Effect of varying doses of tamoxifen on ovarian histopathology, serum VEGF, and
      endothelin 1 levels in ovarian hyperstimulation syndrome: an experimental study.
AB  - OBJECTIVE: To examine the effects of low-to-high doses of tamoxifen on ovarian
      histopathology, serum VEGF, and endothelin 1 levels in ovarian hyperstimulation
      syndrome (OHSS) in an experimental setting. MATERIALS AND METHODS: A total of 20
      female Wistar albino rats, 22 days of age, were randomly divided into four
      groups. Follicle-stimulating hormone 10 IU was administered subcutaneously in 15
      rats on 4 consecutive days, with OHSS induction on day 5 by 30 IU of human
      chorionic gonadotropin. Group 1 (n=5) comprised 35-day-old control rats, group 2
      (n=5) 35-day-old OHSS rats, group 3 (n=5) 27-day-old OHSS rats receiving 1 mg/kg
      of oral tamoxifen for 7 days, group 4 (n=5) 27-day-old OHSS rats receiving 3
      mg/kg of oral tamoxifen for 7 days. All rats were decapitated on day 35. Serum
      VEGF, endothelin 1, and ovarian follicular reserve were assessed in all rats.
      Kruskal-Wallis variance analysis and the Mann-Whitney U-test were used for
      statistical comparisons. A Bonferroni correction was performed to control the
      inflation of significance, with a significance level set at a P-value of less
      than 0.025. RESULTS: Despite higher serum VEGF, endothelin 1, follicular reserve,
      and angiogenesis and fibrosis of the corpus luteum in the OHSS group compared to
      controls, these differences were not significant (P>0.025, Mann-Whitney U-test).
      There was a significant reduction in the ovarian follicular reserve in tamoxifen
      groups compared to controls (P<0.025, Mann-Whitney U-test), while angiogenesis of
      the corpus luteum, number of atretic follicles, fibrosis, and serum VEGF were
      significantly higher in rats receiving tamoxifen (P<0.025, Mann-Whitney U-test).
      Also, significantly lower follicular reserve and fibrosis were observed among
      rats in the low-dose tamoxifen group in comparison with rats in the high-dose
      tamoxifen group (P<0.025, Mann-Whitney U-test). No groups had a significant
      change in endothelin 1 levels (P>0.025, Mann-Whitney U-test). CONCLUSION:
      Tamoxifen 1 g and 3 g resulted in a dose-dependent increase in VEGF and
      endothelin 1 levels, and ovarian follicle reserves were significantly reduced in
      our experimental model.

PMID- 25848213
TI  - Turoctocog alfa: an evidence-based review of its potential in the treatment of
      hemophilia A.
AB  - Turoctocog alfa is the first B-domain-truncated third generation recombinant
      coagulation factor VIII (FVIII) product. Nonclinical in vitro and animal model
      studies have demonstrated that turoctocog alfa has similar functional potency and
      hemostatic efficacy as comparator FVIII products. With respect to discrepancies
      in the level of FVIII concentrate in plasma of current FVIII products on
      comparing measurement results between one-stage clot and chromogenic assays,
      there was no difference in the in vitro turoctocog alfa study; however, measured
      FVIII concentrate in field study was higher with the chromogenic assay (1.08
      IU/mL) than with one-stage assay (0.83 IU/mL). Two published clinical studies on
      previously treated patients (PTPs) and clinical pharmacokinetics have described
      that the pharmacokinetic parameters are similar, and the safety and efficacy for
      prevention and treatment for bleeding are also similar to those of standard half
      life FVIII products. Three clinical trials are ongoing to assess the long-term
      safety and efficacy of turoctocog alfa for PTPs and previously untreated
      patients. Those data will be published in the near future, and it will be
      possible to use turoctocog alfa for all hemophilia patients. However, studies
      will be needed to confirm the turoctocog alfa profile, such as the stability of
      dissolved turoctocog alfa over 24 hours at room temperature and post-marketing
      clinical research aimed at meeting Europe Medicines Agency post-marketing safety
      and efficacy requirements in PTPs. It is recommended to wait before using
      turoctocog alfa for previously untreated patients and major surgery until further
      data have been collected and published.

PMID- 25848214
TI  - Lost expression of ADAMTS5 protein associates with progression and poor prognosis
      of hepatocellular carcinoma.
AB  - Altered expression of ADAMTS5 is associated with human carcinogenesis and tumor
      progression. However, the role of ADAMTS5 in hepatocellular carcinoma (HCC) is
      unclear. This study analyzed ADAMTS5 expression in HCC tissues and tested for
      association with clinicopathological and survival data from HCC patients and then
      explored the role of ADAMTS5 in HCC cells in vitro. Paraffin blocks from 48 HCC
      patients were used to detect ADAMTS5 and vascular endothelial growth factor
      (VEGF) expression and microvessel density (MVD). A normal liver cell line and HCC
      cell lines were used to detect ADAMTS5 expression and for ADAMTS5 manipulation.
      ADAMTS5 cDNA was stably transfected into HCC cells and ADAMTS5 expression
      assessed by Western blot analysis. Tumor cell-conditioned growth medium was used
      to assess human umbilical vein endothelial cell migration and Matrigel tube
      formation. Xenograft assay was performed to determine the role of ADAMTS5 in
      vivo. The data showed that the expression of ADAMTS5 was reduced in HCC, which
      was inversely associated with VEGF expression, MVD, and tumor size and associated
      with poor overall survival of HCC patients. Lentivirus-mediated ADAMTS5
      expression significantly inhibited tumor angiogenesis by downregulating in vitro
      expression of VEGF and inhibiting migration and tube formations, and also
      inhibited tumor growth and VEGF expression and reduced MVD in vivo in a mouse
      xenograft model. Taken together, these results suggest that ADAMTS5 plays a role
      in suppression of HCC progression, which could be further studied as a promising
      novel therapeutic target and a potential prognostic marker in HCC.

PMID- 25848215
TI  - Clinical significance of DAPK promoter hypermethylation in lung cancer: a meta
      analysis.
AB  - Death-associated protein kinase 1 (DAPK) is an important serine/threonine kinase
      involved in various cellular processes, including apoptosis, autophagy, and
      inflammation. DAPK expression and activity are deregulated in a variety of
      diseases including cancer. Methylation of the DAPK gene is common in many types
      of cancer and can lead to loss of DAPK expression. However, the association
      between DAPK promoter hypermethylation and the clinicopathological significance
      of lung cancer remains unclear. In this study, we searched the MEDLINE, PubMed,
      Web of Science, and Scopus databases, systematically investigated the studies of
      DAPK promoter hypermethylation in lung cancer and quantified the association
      between DAPK promoter hypermethylation and its clinicopathological significance
      by meta-analysis. We observed that the frequency of DAPK methylation was
      significantly higher in lung cancer than in non-malignant lung tissues (odds
      ratio 6.02, 95% confidence interval 3.17-11.42, P<0.00001). The pooled results
      also showed the presence of a prognostic impact of DAPK gene methylation in lung
      cancer patients (odds ratio 3.63, 95% confidence interval 1.09-12.06, P=0.04). In
      addition, we summarized these findings and discuss tumor suppressor function,
      clinicopathological significance, and potential drug targeting of DAPK in lung
      cancer.

PMID- 25848216
TI  - Recent progress in fungus-derived bioactive agents for targeting of signaling
      machinery in cancer cells.
AB  - It is becoming increasingly understood that tumor cells may have different
      mutations and dependencies on diverse intracellular signaling cascades for
      survival or metastatic potential. Overexpression of oncogenes, inactivation of
      tumor suppressor genes, genetic/epigenetic mutations, genomic instability, and
      loss of apoptotic cell death are some of the mechanisms that have been widely
      investigated in molecular oncology. We partition this multicomponent review into
      the most recent evidence on the anticancer activity of fungal substances obtained
      from in vitro and xenografted models, and these fungal substances modulate
      expression of oncogenic and tumor suppressor miRNAs. There are some outstanding
      questions regarding fungus-derived chemical-induced modulation of intracellular
      signaling networks in different cancer cell lines and preclinical models. Certain
      hints have emerged, emphasizing mechanisms via which apoptosis can be restored in
      TRAIL-resistant cancer cells. Reconceptualization of the knowledge obtained from
      these emerging areas of research will enable us to potentially identify natural
      agents with notable anticancer activity and minimal off-target effects.
      Integration of experimentally verified evidence obtained from cancer cell line
      gene expression with large-scale functional screening results and pharmacological
      sensitivity data will be helpful in identification of therapeutics with
      substantial efficacy. New tools and technologies will further deepen our
      understanding of the signaling networks that underlie the development of cancer,
      metastasis, and resistance to different therapeutics at both a personal and
      systems-wide level.

PMID- 25848217
TI  - Novel nanoliposomal delivery system for polydatin: preparation, characterization,
      and in vivo evaluation.
AB  - BACKGROUND: The objective of this study was to develop a novel polydatin (PLD)
      loaded liposome system using the thin film hydration technique. METHODS: The
      delivery system was characterized in terms of morphology, size, zeta potential,
      encapsulation efficiency, and in vitro release. In addition, a pharmacokinetic
      study was carried out in rats after oral administration of PLD-loaded liposomes
      in vivo. RESULTS: Transmission electron microscopy revealed that the PLD-loaded
      liposomes had a homogeneous size and spherical shape. Dynamic light scattering
      showed that the PLD-loaded liposomes had a smaller size with a mean value of
      80.2+/-3.7 nm and a polydispersity index of 0.12+/-0.06. The encapsulation
      efficiency of the prepared liposomes was 88.4%+/-3.7%. During the release
      process, liposome showed two distinct phases. The first was characterized by
      rapid release during the first 2 hours, which could be related to the release of
      the drug adsorbed on the surface of liposomes. In the second phase, the release
      rate slowed down, demonstrating a typical sustained and prolonged drug-release
      behavior. The release kinetic model for the PLD-loaded liposomes fitted well with
      the Weibull distribution equation. In vivo, relative oral bioavailability of the
      encapsulated PLD was 282.9%, ie, significantly enhanced (P<0.05) compared with
      the free drug. No histological changes occurred in the organs after
      administration of PLD-loaded liposomes. CONCLUSION: PLD-loaded liposomes could
      significantly prolong the drug circulation time in vivo and increase the oral
      bioavailability of the drug.

PMID- 25848218
TI  - Paracellular permeation-enhancing effect of AT1002 C-terminal amidation in nasal
      delivery.
AB  - BACKGROUND: The identification of permeation enhancers has gained interest in the
      development of drug delivery systems. A six-mer peptide, H-FCIGRL-OH (AT1002), is
      a tight junction modulator with promising permeation-enhancing activity. AT1002
      enhances the transport of molecular weight markers or agents with low
      bioavailability with no cytotoxicity. However, AT1002 is not stable in neutral pH
      or after incubation under physiological conditions, which is necessary to fully
      uncover its permeation-enhancing effect. Thus, we increased the stability or
      mitigated the instability of AT1002 by modifying its terminal amino acids and
      evaluated its subsequent biological activity. METHODS: C-terminal-amidated
      (FCIGRL-NH2, Pep1) and N-terminal-acetylated (Ac-FCIGRL, Pep2) peptides were
      analyzed by liquid chromatography-mass spectrometry. We further assessed
      cytotoxicity on cell monolayers, as well as the permeation-enhancing activity
      following nasal administration of the paracellular marker mannitol. RESULTS: Pep1
      was nontoxic to cell monolayers and showed a relatively low decrease in peak area
      compared to AT1002. In addition, administration of mannitol with Pep1 resulted in
      significant increases in the area under the plasma concentration-time curve and
      peak plasma concentration at 3.63-fold and 2.68-fold, respectively, compared to
      mannitol alone. In contrast, no increase in mannitol concentration was shown with
      mannitol/AT1002 or mannitol/Pep2 compared to the control. Thus, Pep1 increased
      the stability or possibly reduced the instability of AT1002, which resulted in an
      increased permeation-enhancing effect of AT1002. CONCLUSION: These results
      suggest the potential usefulness of C-terminal-amidated AT1002 in enhancing nasal
      drug delivery, which may lead to the development of a practical drug delivery
      technology for drugs with low bioavailability.

PMID- 25848219
TI  - Pharmacoinformatics approach for investigation of alternative potential hepatitis
      C virus nonstructural protein 5B inhibitors.
AB  - Hepatitis C virus (HCV) is one of the major viruses affecting the world today. It
      is a highly variable virus, having a rapid reproduction and evolution rate. The
      variability of genomes is due to hasty replication catalyzed by nonstructural
      protein 5B (NS5B) which is also a potential target site for the development of
      anti-HCV agents. Recently, the US Food and Drug Administration approved
      sofosbuvir as a novel oral NS5B inhibitor for the treatment of HCV.
      Unfortunately, it is much highlighted for its pricing issues. Hence, there is an
      urgent need to scrutinize alternate therapies against HCV that are available at
      affordable price and do not have associated side effects. Such a need is crucial
      especially in underdeveloped countries. The search for various new bioactive
      compounds from plants is a key part of pharmaceutical research. In the current
      study, we applied a pharmacoinformatics-based approach for the identification of
      active plant-derived compounds against NS5B. The results were compared to docking
      results of sofosbuvir. The lead compounds with high-binding ligands were further
      analyzed for pharmacokinetic and pharmacodynamic parameters based on in silico
      absorption, distribution, metabolism, excretion, and toxicity (ADMET) profile.
      The results showed the potential alternative lead compounds that can be developed
      into commercial drugs having high binding energy and promising ADMET properties.

PMID- 25848220
TI  - Design and evaluation of effervescent floating tablets based on hydroxyethyl
      cellulose and sodium alginate using pentoxifylline as a model drug.
AB  - The aim of this work was to design and evaluate effervescent floating gastro
      retentive drug delivery matrix tablets with sustained-release behavior using a
      binary mixture of hydroxyethyl cellulose and sodium alginate. Pentoxifylline was
      used as a highly water-soluble, short half-life model drug with a high density.
      The floating capacity, swelling, and drug release behaviors of drug-loaded matrix
      tablets were evaluated in 0.1 N HCl (pH 1.2) at 37 degrees C+/-0.5 degrees C.
      Release data were analyzed by fitting the power law model of Korsmeyer-Peppas.
      The effect of different formulation variables was investigated, such as wet
      granulation, sodium bicarbonate gas-forming agent level, and tablet hardness
      properties. Statistical analysis was applied by paired sample t-test and one-way
      analysis of variance depending on the type of data to determine significant
      effect of different parameters. All prepared tablets through wet granulation
      showed acceptable physicochemical properties and their drug release profiles
      followed non-Fickian diffusion. They could float on the surface of dissolution
      medium and sustain drug release over 24 hours. Tablets prepared with 20% w/w
      sodium bicarbonate at 50-54 N hardness were promising with respect to their
      floating lag time, floating duration, swelling ability, and sustained drug
      release profile.

PMID- 25848221
TI  - Comparative efficacy of pitavastatin and simvastatin in patients with
      hypercholesterolemia: a meta-analysis of randomized controlled clinical trials.
AB  - BACKGROUND: Simvastatin is a statin used to lower low-density lipoprotein
      cholesterol, but has limitations in patients on complicated regimens due to
      concerns about drug-drug interactions. Pitavastatin is a newly developed statin
      with limited drug-drug interactions. We conducted a meta-analysis to compare the
      clinical efficacy of simvastatin and pitavastatin in the control of
      hypercholesterolemia. METHODS: Randomized clinical trials comparing the efficacy
      of pitavastatin and simvastatin were identified by searching PubMed (2000-2014)
      and EMBASE (2000-2014). The primary outcome subjected to meta-analysis was
      percent change in low-density lipoprotein cholesterol compared with baseline.
      RESULTS: Four clinical trials were selected for meta-analysis. A total of 908
      patients treated with pitavastatin (2 or 4 mg/day) and 381 patients treated with
      simvastatin (20 or 40 mg/day) were included in the final statistical analysis. No
      statistically significant difference was identified between treatment with
      pitavastatin 4 mg/day and treatment with simvastatin 40 mg/day for 12 weeks (mean
      difference -0.66; 95% confidence interval -2.92, 1.61; P=0.57). Similarly, no
      statistically significant difference was observed between pitavastatin 2 mg/day
      and simvastatin 20 mg/day for 4 weeks (mean difference -2.19; 95% confidence
      interval -0.11, 4.49; P=0.06). Treatment with pitavastatin was noninferior to
      simvastatin in all of the secondary outcomes and the safety profile was similar
      between the two statins. CONCLUSION: Pitavastatin is noninferior to simvastatin
      in lowering low-density lipoprotein cholesterol.

PMID- 25848222
TI  - Liraglutide and obesity: a review of the data so far.
AB  - The prevalence of obesity worldwide has nearly doubled since 1980 with current
      estimates of 2.1 billion in 2013. Overweight and obesity lead to numerous adverse
      conditions including type 2 diabetes, cardiovascular disease, stroke, and certain
      cancers. The worldwide spread of obesity and associated comorbidities not only
      threatens quality of life but also presents a significant economic burden. While
      bariatric surgery has proven to be a viable treatment option for the morbidly
      obese, there is clearly a need for less invasive alternatives. Recent research
      has suggested that long-acting analogs of the gut hormone, glucagon-like peptide
      1 (GLP-1), may have potential as an antiobesity treatment. The GLP-1 receptor
      agonist, liraglutide (trade name Saxenda), was recently approved by the US Food
      and Drug Administration as an obesity treatment option and shown in clinical
      trials to be effective in reducing and sustaining body weight loss. This review
      presents the basis for GLP-1-based therapies with a specific focus on animal and
      human studies examining liraglutide's effects on food intake and body weight.

PMID- 25848223
TI  - A perspective on the benefit-risk assessment for new and emerging pharmaceuticals
      in Japan.
AB  - The universal health care system in Japan is facing a historical turning point as
      a result of the increasing fiscal burden, rapidly aging society, and a decreasing
      population. To understand the challenges and opportunities in the Japanese
      pharmaceutical market, which occupies one tenth of the global share, this review
      highlights several issues related to the benefit-risk assessment that is unique
      to the modern Japanese society: 1) regulatory system for new drug development; 2)
      health hazards related to pharmaceuticals ("Yakugai" in Japanese); 3) drug lag;
      4) problems and controversies in the vaccination policy; and 5) clinical study
      misconduct. The regulatory process places a significant importance on Japanese
      data collection regardless of data accumulation from other countries. Because
      Yakugai has repeatedly caused tragedies and social disputes historically, the
      regulatory judgments generally tend to be more prudential when safety concerns
      are raised for new and emerging pharmaceuticals. Such a regulatory system has
      caused more than several years of approval delays compared to delays in other
      countries. The problem of drug lag still lingers on despite several regulatory
      system revisions, while the solution is incompatible with the elimination of
      Yakugai because the lag potentially reduces the risk of unpredictable adverse
      events. The Japanese vaccination policy has also received a lot of criticism, and
      needs improvements so that the decision-making process can be more transparent
      and scientifically based. Additionally, repeated clinical study misconduct
      damaged the reputation of Japanese clinical studies with unnecessary defrayment
      in health insurance; therefore, the medical community must change its
      inappropriate relationship with the industry. The problems surrounding
      pharmaceuticals are related to centralized, strict drug pricing control under the
      universal health coverage. Although the current government attempts to facilitate
      innovative research and development of novel therapeutics in Japan, further
      reforms should be explored for patients who need new and emerging
      pharmaceuticals. 

PMID- 25848224
TI  - Visual detection of glial cell line-derived neurotrophic factor based on a
      molecular translator and isothermal strand-displacement polymerization reaction.
AB  - BACKGROUND: Glial cell line-derived neurotrophic factor (GDNF) is a small protein
      that potently promotes the survival of many types of neurons. Detection of GDNF
      is vital to monitoring the survival of sympathetic and sensory neurons. However,
      the specific method for GDNF detection is also un-discovered. The purpose of this
      study is to explore the method for protein detection of GDNF. METHODS: A novel
      visual detection method based on a molecular translator and isothermal strand
      displacement polymerization reaction (ISDPR) has been proposed for the detection
      of GDNF. In this study, a molecular translator was employed to convert the input
      protein to output deoxyribonucleic acid signal, which was further amplified by
      ISDPR. The product of ISDPR was detected by a lateral flow biosensor within 30
      minutes. RESULTS: This novel visual detection method based on a molecular
      translator and ISDPR has very high sensitivity and selectivity, with a dynamic
      response ranging from 1 pg/mL to 10 ng/mL, and the detection limit was 1 pg/mL of
      GDNF. CONCLUSION: This novel visual detection method exhibits high sensitivity
      and selectivity, which is very simple and universal for GDNF detection to help
      disease therapy in clinical practice.

PMID- 25848226
TI  - Association of orthodontic treatment needs and oral health-related quality of
      life.

PMID- 25848225
TI  - Modeling, molecular dynamics, and docking assessment of transcription factor rho:
      a potential drug target in Brucella melitensis 16M.
AB  - The zoonotic disease brucellosis, a chronic condition in humans affecting renal
      and cardiac systems and causing osteoarthritis, is caused by Brucella, a genus of
      Gram-negative, facultative, intracellular pathogens. The mode of transmission and
      the virulence of the pathogens are still enigmatic. Transcription regulatory
      elements, such as rho proteins, play an important role in the termination of
      transcription and/or the selection of genes in Brucella. Adverse effects of the
      transcription inhibitors play a key role in the non-successive transcription
      challenges faced by the pathogens. In the investigation presented here, we
      computationally predicted the transcription termination factor rho (TtFRho)
      inhibitors against Brucella melitensis 16M via a structure-based method. In view
      the unknown nature of its crystal structure, we constructed a robust three
      dimensional homology model of TtFRho's structure by comparative modeling with the
      crystal structure of the Escherichia coli TtFRho (Protein Data Bank ID: 1PVO) as
      a template in MODELLER (v 9.10). The modeled structure was optimized by applying
      a molecular dynamics simulation for 2 ns with the CHARMM (Chemistry at HARvard
      Macromolecular Mechanics) 27 force field in NAMD (NAnoscale Molecular Dynamics
      program; v 2.9) and then evaluated by calculating the stereochemical quality of
      the protein. The flexible docking for the interaction phenomenon of the template
      consists of ligand-related inhibitor molecules from the ZINC (ZINC Is Not
      Commercial) database using a structure-based virtual screening strategy against
      minimized TtFRho. Docking simulations revealed two inhibitors compounds -
      ZINC24934545 and ZINC72319544 - that showed high binding affinity among 2,829
      drug analogs that bind with key active-site residues; these residues are
      considered for protein-ligand binding and unbinding pathways via steered
      molecular dynamics simulations. Arg215 in the model plays an important role in
      the stability of the protein-ligand complex via a hydrogen bonding interaction by
      aromatic-pi contacts, and the ADMET (absorption, distribution, metabolism, and
      excretion) analysis of best leads indicate nontoxic in nature with good potential
      for drug development.

PMID- 25848227
TI  - The German version of the Individualized Care Scale - assessing validity and
      reliability.
AB  - AIM: To assess validity and reliability of the German version of the
      Individualized Care Scale (ICS). BACKGROUND: Individualized nursing care plays a
      pivotal role in establishing patient-centered care. To assess individualized
      nursing care and to compare it in different settings and countries, valid and
      reliable instruments are needed. No psychometric-tested instrument for comparing
      individualized nursing care with other countries is available in Germany. DESIGN:
      Cross-sectional study. METHODS: Data were collected between September 2013 and
      June 2014 from 606 patients in 20 wards in five hospitals across Germany.
      Unidimensionality of the ICS scales ICSA (patients' views on how individuality is
      supported through nursing interventions) and ICSB (patients' perceptions of
      individualized nursing care) was analyzed by confirmatory factor analysis.
      Internal consistency was assessed by calculating Cronbach's alpha. The Smoliner
      Scale (patients' perceptions of the decision-making process in nursing care) and
      results from participating hospitals' assessment of the nursing care delivery
      systems were used to assess known-groups validity and concurrent validity.
      RESULTS: Fit indices of confirmatory factor analysis indicate unidimensionality
      of the ICSA (Comparative Fit Index: 0.92; Tucker-Lewis Index: 0.902; root mean
      square error of approximation: 0.09; standardized root mean square residual:
      0.05) and the ICSB (Comparative Fit Index: 0.91; Tucker-Lewis Index: 0.89; root
      mean square error of approximation: 0.09; standardized root mean square residual:
      0.05). Internal consistency using Cronbach's alpha was 0.95 (95% confidence
      interval: 0.94-0.95) for ICSA and 0.93 (95% confidence interval: 0.92-0.94) for
      the ICSB. Concurrent validity was established by a significant relationship
      between the Smoliner Scale and ICSA (r=0.66; P<0.01) and ICSB (r=0.72; P<0.01).
      Known-groups validity was approved by ICSA/ICSB score differences related to
      nursing care delivery systems and patients' perceptions of decision-making style.
      CONCLUSION: The German version of the ICS is deemed a valid and reliable
      instrument for use in practice and research with hospitalized patients.

PMID- 25848228
TI  - Electronic health records and improved nursing management of chronic obstructive
      pulmonary disease.
AB  - This paper identifies evolving trends in the diagnosis and treatment of chronic
      obstructive pulmonary disease (COPD), and recommends the integration of nursing
      strategies in COPD management via widespread implementation of electronic health
      records. COPD is a complex lung disease with diverse origins, both physical and
      behavioral, manifested in a wide range of symptoms that further increase the
      patient's risk for comorbidities. Early diagnosis and effective management of
      COPD require monitoring of a dizzying array of COPD symptoms over extended
      periods of time, and nurses are especially well positioned to manage potential
      progressions of COPD, as frontline health care providers who obtain, record, and
      organize patient data. Developments in medical technology greatly aid nursing
      management of COPD, from the deployment of spirometry as a diagnostic tool at the
      family practice level to newly approved treatment options, including non-nicotine
      pharmacotherapies that reduce the cravings associated with tobacco withdrawal.
      Among new medical technologies, electronic health records have proven
      particularly advantageous in the management of COPD, enabling providers to
      gather, maintain, and reference more patient data than has ever been possible
      before. Thus, consistent and widespread implementation of electronic health
      records facilitates the coordination of diverse treatment strategies, resulting
      in increased positive health outcomes for patients with COPD. 

PMID- 25848229
TI  - Exploring barriers to the delivery of cervical cancer screening and early
      treatment services in Malawi: some views from service providers.
AB  - BACKGROUND: Cervical cancer is the most common reproductive health cancer in
      Malawi. In most cases, women report to health facilities when the disease is in
      its advanced stage. In this study, we investigate service providers' perceptions
      about barriers for women to access cervical cancer screening and early treatment
      services in Malawi. METHODS: We conducted in-depth interviews with 13 district
      coordinators and 40 service providers of cervical cancer screening and early
      treatment services in 13 districts in Malawi. The study was conducted in 2012.
      The district coordinators helped the research team identify the health facilities
      which were providing cervical cancer screening and early treatment services.
      RESULTS: Almost all informants reported that cervical cancer was a major public
      health problem in their districts and that prevention efforts for this disease
      were being implemented. They were aware of the test and treat approach using
      visual inspection with acetic acid (VIA). They, however, said that the delivery
      of cervical cancer screening and early treatment services was compromised because
      of factors such as gross shortage of staff, lack of equipment and supplies, the
      lack of supportive supervision, and the use of male service providers. Informants
      added that the lack of awareness about the disease among community members, long
      distances to health facilities, the lack of involvement of husbands, and
      prevailing misperceptions about the disease (eg, that it is caused by the
      exposure to the VIA process) affect the uptake of these services. CONCLUSION:
      While progress has been made in the provision of cervical cancer screening and
      early treatment services in Malawi, a number of factors affect service delivery
      and uptake. There is a need to continue creating awareness among community
      members including husbands and also addressing identified barriers such as
      shortage of staff and supplies in order to improve uptake of services.

PMID- 25848230
TI  - Development of the CoMac Adherence DescriptorTM: a linguistically-based survey
      for segmenting patients on their worldviews.
AB  - Nonadherence to prescribed medication and healthy behaviors is a pressing health
      care issue. Much research has been conducted in this area under a variety of
      labels, such as compliance, disease management and, most recently, adherence.
      However, the complex factors related to predicting and, more importantly,
      understanding and explaining adherence, have nevertheless remained elusive.
      However, through an in-depth linguistic analysis of patient talk, the
      International Center for Intercultural Communication (ICIC) at Indiana University
      has produced a psycholinguistic coding system that uses patients' own language to
      cluster them into distinct groups based on their worldviews. ICIC's studies have
      shown, for example, that patients reveal their fundamental perceptions about
      themselves and their environment in their life narratives; clustering of
      individual patients based on these different perceptions is possible via the use
      of differential language in survey questions, and differential language can be
      used to tailor messages for individual patients in a manner that these
      individuals prefer over generically worded communication. In grant-funded
      research, an interdisciplinary team of researchers at the ICIC reviewed the
      literature and identified three basic psychosocial tenets related to adherence:
      control orientation, based on locus of control research; agency, based on self
      efficacy; and affect or attitude and emotion. These three constructs were
      selected because, in the published literature, they have been consistently found
      to be connected to patient adherence. Based on this research, a survey, the CoMac
      DescriptorTM was developed. This report shows that The DescriptorTM questions and
      responses are valid and reliable in segmenting patients across psychosocial
      constructs, which will have positive implications for health care providers and
      patients. 

PMID- 25848231
TI  - Simplicity, safety, and acceptability of insulin pen use versus the conventional
      vial/syringe device in patients with type 1 and type 2 diabetes mellitus in
      Lebanon.
AB  - BACKGROUND: The aim of the study was to evaluate the simplicity, safety,
      patients' preference, and convenience of the administration of insulin using the
      pen device versus the conventional vial/syringe in patients with diabetes.
      METHODS: This observational study was conducted in multiple community pharmacies
      in Lebanon. The investigators interviewed patients with diabetes using an insulin
      pen or conventional vial/syringe. A total of 74 questionnaires were filled over a
      period of 6 months. Answers were entered into the Statistical Package for Social
      Sciences (SPSS) software and Excel spreadsheet. t-test, logistic regression
      analysis, and correlation analysis were used in order to analyze the results.
      RESULTS: A higher percentage of patients from the insulin pen users group (95.2%)
      found the method easy to use as compared to only 46.7% of the insulin
      conventional users group (P 0.001, relative risk [RR]: 2.041, 95% confidence
      interval [CI]: 1.178-3.535). Moreover, 61.9% and 26.7% of pen users and
      conventional users, respectively, could read the scale easily (P 0.037, RR 2.321,
      95% CI: 0.940-5.731), while 85.7% of pen users found it more convenient shifting
      to pen and 86.7% of the conventional users would want to shift to pen if it had
      the same cost. Pain perception was statistically different between the groups. A
      much higher percentage (76.2%) of pen users showed no pain during injection
      compared to only 26.7% of conventional users (P 0.003, RR 2.857, 95% CI: 1.194
      6.838). CONCLUSION: The insulin pen was significantly much easier to use and less
      painful than the conventional vial/syringe. Proper education on the methods of
      administration/storage and disposal of needles/syringes is needed in both groups.

PMID- 25848232
TI  - More than what the eye can see: the emotional journey and experience of
      powerlessness of integrated care service users and their carers.
AB  - PURPOSE: This article presents the emotional journey and experience of
      powerlessness of integrated care service users and carers. MATERIALS AND METHODS:
      The experiences of seven integrated care service users and carers affected by
      complex conditions in a London borough were captured as video stories. The
      integrated care service coordinated a system of health and social care: primary
      care, community matrons, social workers, and the voluntary sector. The service
      was designed to respond to identified cases of high-risk individuals with long
      term, multiple, and age-related conditions needing preventive interventions. The
      video stories were analyzed by researchers in collaboration with service users
      using a visual thematic qualitative approach. This report is part of an
      independent analysis of the integrated care service evaluation that used the
      experience-based codesign model. RESULTS: The findings are presented in the
      respective contexts of people with complex conditions and their carers. The
      overwhelming feelings and emotions of both were loss of control and power
      throughout their emotional journey, with family carers adopting a protective
      attitude toward the patients. Their experience of powerlessness was variable
      throughout their emotional journey. They were affected more strongly when in need
      of extra help and support and while they were undergoing the process of receiving
      extra services. When they were receiving help and support outside and within
      hospitals, some participants were empowered, gaining skills and knowledge by
      being provided with the mechanisms to cope with their condition at present and in
      the future. CONCLUSION: Feelings of powerlessness were very common among
      integrated care service users and their carers. Powerless/empowerment has been
      poorly investigated to date. Visual methods and collaborative visual analysis
      with service users have proved to be powerful methods too, but have been rarely
      reported.

PMID- 25848233
TI  - Skills-based medication training program for patients with schizophrenic
      disorders: a rater-blind randomized controlled trial.
AB  - BACKGROUND: The long-term course of schizophrenia is often characterized by
      relapses, induced by poor medication adherence. Early nonadherence after
      discharge is frequent. OBJECTIVE: To evaluate a skills-based inpatient training
      program for medication intake. METHODS: We developed a manual-based inpatient
      medication training program to be carried out by nurses and focusing on practical
      skills enabling autonomous intake of medication. Medication adherence was
      measured by three different methods: pill count, determination of serum levels,
      and self-assessment by the patient. The raters were blinded. RESULTS: Four weeks
      after discharge, 98% of the patients in the intervention group (N=52) were rated
      as adherent by pill count versus 76% in the control group (N=50; P<0.01). By
      measurement of serum level, 88.5% versus 70% were adherent (P<0.05). CONCLUSION:
      The inpatient medication training program carried out by nurses seems to be an
      effective intervention for enhancing medication adherence after hospital
      discharge.

PMID- 25848234
TI  - The epidemiology and management of postmenopausal osteoporosis: a viewpoint from
      Brazil.
AB  - Brazil has an aging population, with an associated increase in the prevalence of
      chronic diseases. Postmenopausal osteoporosis is of particular concern because it
      leads to an increased risk of fractures, with subsequent negative impacts on
      health in older women. In recent years, efforts have been made to better
      understand the epidemiology of osteoporosis in Brazil, and to manage both direct
      and indirect costs to the Brazilian health care system. The reported prevalence
      of osteoporosis among postmenopausal women in Brazil varies from 15% to 33%,
      depending on the study methodology and the use of bone densitometry data or self
      reporting by participants. A diagnosis of osteoporosis can be made on the basis
      of fractures occurring without significant trauma or on the basis of low bone
      mineral density measured by dual energy X-ray absorptiometry. To reduce the risk
      of osteoporosis, all postmenopausal women should be encouraged to maintain a
      healthy lifestyle, which includes physical activity and a balanced diet. Smoking
      and alcohol use should also be addressed. Special attention should be given to
      interventions to reduce the risk of falls, especially among older women. Calcium
      intake should be encouraged, preferably through diet. The decision to recommend
      calcium supplementation should be made individually because there is concern
      about a possible increased risk of cardiovascular disease associated with this
      treatment. Brazilian women obtain a minimal amount of vitamin D from their diet,
      and supplementation is warranted in women with little exposure to solar
      ultraviolet-B radiation. For women diagnosed with osteoporosis, some form of
      pharmacologic therapy should be initiated. Compliance with treatment should be
      monitored, and the treatment period should be individualized for each patient.
      The Brazilian government provides medication for osteoporosis through the public
      health system free of charge, but without proper epidemiological knowledge, the
      implementation of public health programs is impaired. 

PMID- 25848235
TI  - Respiratory training as strategy to prevent cognitive decline in aging: a
      randomized controlled trial.
AB  - BACKGROUND: Inadequate oxygenation may cause lesions and brain atrophy during
      aging. Studies show a positive association between pulmonary function and the
      cognitive performance of individuals from middle age on. OBJECTIVE: To
      investigate the effect of aerobic physical exercises and respiratory training on
      the blood oxygenation, pulmonary functions, and cognition of the elderly. DESIGN:
      This was a randomized and controlled trial with three parallel groups. A total of
      195 community-dwelling elderly were assessed for eligibility; only n=102 were
      included and allocated into the three groups, but after 6 months, n=68 were
      analyzed in the final sample. Participants were randomized into a social
      interaction group (the control group), an aerobic exercise group (the "walking"
      group), or a respiratory training group (the "breathing" group). The main outcome
      measures were the Wechsler Adult Intelligence Scale, Wechsler Memory Scale,
      Wisconsin Card Sorting Test, respiratory muscular strength, cirtometry (thoracic
      abdominal circumference); oxygen saturation in arterial blood (SpO2), and
      hemogram. RESULTS: No differences were observed for any of the blood parameters.
      Aerobic exercise and respiratory training were effective in improving the
      pulmonary parameters. Better cognitive performance was observed for the breathing
      group as regards abstraction and mental flexibility. The walking group remained
      stable in the cognitive performance of most of the tests, except attention. The
      control group presented worst performance in mental manipulation of information,
      abstraction, mental flexibility, and attention. CONCLUSION: Our results showed
      that both the walking and breathing groups presented improvement of pulmonary
      function. However, only the breathing group showed improved cognitive function
      (abstraction, mental flexibility). The improvement in cognitive functions cannot
      be explained by blood parameters, such as SpO2, erythrocytes, hemoglobin, and
      hematocrit.

PMID- 25848236
TI  - Monocyte chemoattractant protein-1: a proinflammatory cytokine elevated in
      sarcopenic obesity.
AB  - OBJECTIVE: Sarcopenic obesity (SO) is associated with poorer physical outcomes
      and functional status in the older adult. A proinflammatory milieu associated
      with central obesity is postulated to enhance muscle catabolism. We set out to
      examine associations of the chemokine monocyte chemoattractant protein-1 (MCP-1)
      in groups of older adults, with sarcopenia, obesity, and the SO phenotypes.
      METHODS: A total of 143 community dwelling, well, older adults were recruited.
      Cross-sectional clinical data, physical performance, and muscle mass measurements
      were collected. Obesity and sarcopenia were defined using revised National
      Cholesterol Education Program (NCEP) obesity guidelines and those of the Asian
      Working Group for Sarcopenia. Serum levels of MCP-1 were measured by enzyme
      linked immunosorbent assay (ELISA). RESULTS: In all, 25.2% of subjects were
      normal, 15.4% sarcopenic, 48.3% obese, and 11.2% were SO. The SO groups had the
      lowest appendicular lean mass, highest percentage body fat, and lowest
      performance scores on the Short Physical Performance Battery and grip strength.
      The MCP-1 levels were significantly different, with the highest levels found in
      SO participants (P<0.05). CONCLUSION: Significantly raised MCP-1 levels in obese
      and SO subjects support the theory of chronic inflammation due to excess
      adiposity. Longitudinal studies will reveal whether SO represents a continuum of
      obesity causing accelerated sarcopenia and cardiovascular events, or the
      coexistence of two separate conditions with synergistic effects affecting
      functional performance.

PMID- 25848237
TI  - Behavioral activation for dementia caregivers: scheduling pleasant events and
      enhancing communications.
AB  - BACKGROUND: Dementia caregiving is often associated with increase in depressive
      symptoms and strained relationships. This study tested whether telephone
      delivered psychoeducation combined with an enhanced behavioral activation (BA)
      module had a better effect on the well-being of Alzheimer's caregivers than
      psychoeducation alone. The focus is on enhancing the competent use of coping
      skills via BA. The program is delivered by telephone to increase accessibility
      and sustainability for caregivers. Senior citizens are trained as
      paraprofessionals to deliver the BA module to increase the potential for
      sustainability of the program. METHODS AND SUBJECTS: The study compared two
      telephone interventions using a 4-month longitudinal randomized controlled trial.
      For the first 4 weeks, all participants received the same psychoeducation program
      via telephone. Then for the following 4 months, eight biweekly telephone follow
      up calls were carried out. For these eight follow-up calls, participants were
      randomized into either one of the two following groups with different conditions.
      For the psychoeducation with BA (PsyED-BA) group, participants received eight
      biweekly sessions of BA practice focused on pleasant event scheduling and
      improving communications. For the psychoeducation only (PsyED only) group,
      participants received eight biweekly sessions of general discussion of
      psychoeducation and related information. A total of 62 family caregivers of
      persons living with dementia were recruited and 59 (29 in the PsyED-BA group and
      30 in the PsyED only group) completed the whole study. RESULTS: As compared to
      the group with psychoeducation and discussion, the group with enhanced BA had
      decreased levels of depressive symptoms. The study had a low attrition rate.
      CONCLUSION: Results suggested that competence-based training could be effectively
      administered through the telephone with the help of senior citizens trained and
      engaged as paraprofessionals. Results contribute to the present literature by
      offering some framework for developing effective, accessible, sustainable, and
      less costly interventions.

PMID- 25848238
TI  - Personalized therapeutics of alpha1-blockers in patients with lower urinary tract
      symptoms suggestive of benign prostatic hyperplasia.

PMID- 25848239
TI  - Cognitive fluctuations in connection to dysgraphia: a comparison of Alzheimer's
      disease with dementia Lewy bodies.
AB  - BACKGROUND: The purpose of the present study was to examine the relationship
      between cognitive impairment and the performance of handwritten scripts presented
      as "letter-writing" to a close relative by patients with dementia Lewy bodies
      (DLB), as fluctuations of the symptoms phase, and in a matched group of patients
      with Alzheimer's disease (AD). The degree of writing disability and personal,
      spatial, and temporal orientation was compared in these two groups. DESIGN AND
      METHODS: Fourteen simple questions, designed in a form that could be utilized by
      any general practitioner in order to document the level of cognitive functioning
      of each patient, were presented to 30 AD patients and 26 DLB patients. The
      initial cognition test was designated PQ1. The patients were examined on tests of
      letter-writing ability. Directly after the letter-writing, the list of 14
      questions presented in PQ1 was presented again in a repeated procedure that was
      designated PQ2. The difference between these two measures (PQ1 - PQ2) was
      designated DDelta. This test of letter-writing ability and cognitive performance
      was administered over 19 days. RESULTS: Several markedly strong relationships
      between dysgraphia and several measures of cognitive performance in AD patients
      and DLB patients were observed, but the deterioration of performance from PQ1 to
      PQ2 over all test days were markedly significant in AD patients and not
      significant in DLB patients. It is possible that in graphic expression even by
      patients diagnosed with moderate to relatively severe AD and DLB there remains
      some residual capacity for understanding and intention that may be expressed.
      Furthermore, the deterioration in performance and the differences noted in AD and
      DLB patients may be due to the different speed at which the process of the
      protein degradation occurs for functional modification of synapses. CONCLUSION:
      Our method can be used as part of neuropsychological tests to differentiate the
      diagnosis between AD and DLB.

PMID- 25848240
TI  - Repeated vertebral augmentation for new vertebral compression fractures of
      postvertebral augmentation patients: a nationwide cohort study.
AB  - PURPOSE: Postvertebral augmentation vertebral compression fractures are common;
      repeated vertebral augmentation is usually performed for prompt pain relief. This
      study aimed to evaluate the incidence and risk factors of repeat vertebral
      augmentation. METHODS: We performed a retrospective, nationwide, population-based
      longitudinal observation study, using the National Health Insurance Research
      Database (NHIRD) of Taiwan. All patients who received vertebral augmentation for
      vertebral compression fractures were evaluated. The collected data included
      patient characteristics (demographics, comorbidities, and medication exposure)
      and repeat vertebral augmentation. Kaplan-Meier and stratified Cox proportional
      hazard regressions were performed for analyses. RESULTS: The overall incidence of
      repeat vertebral augmentation was 11.3% during the follow-up until 2010. Patients
      with the following characteristics were at greater risk for repeat vertebral
      augmentation: female sex (AOR=1.24; 95% confidence interval [CI]: 1.10-2.36),
      advanced age (AOR=1.60; 95% CI: 1.32-2.08), diabetes mellitus (AOR=4.31; 95% CI:
      4.05-5.88), cerebrovascular disease (AOR=4.09; 95% CI: 3.44-5.76), dementia
      (AOR=1.97; 95% CI: 1.69-2.33), blindness or low vision (AOR=3.72; 95% CI: 2.32
      3.95), hypertension (AOR=2.58; 95% CI: 2.35-3.47), and hyperlipidemia (AOR=2.09;
      95% CI: 1.67-2.22). Patients taking calcium/vitamin D (AOR=2.98; 95% CI: 1.83
      3.93), bisphosphonates (AOR=2.11; 95% CI: 1.26-2.61), or calcitonin (AOR=4.59;
      95% CI: 3.40-5.77) were less likely to undergo repeat vertebral augmentation;
      however, those taking steroids (AOR=7.28; 95% CI: 6.32-8.08), acetaminophen
      (AOR=3.54; 95% CI: 2.75-4.83), or nonsteroidal anti-inflammatory drugs (NSAIDs)
      (AOR=6.14; 95% CI: 5.08-7.41) were more likely to undergo repeat vertebral
      augmentation. CONCLUSION: We conclude that the incidence of repeat vertebral
      augmentation is rather high. An understanding of risk factors predicting repeat
      vertebral augmentation provides valuable basis to improve health care for
      geriatric populations.

PMID- 25848241
TI  - Home-based pulmonary rehabilitation improves clinical features and systemic
      inflammation in chronic obstructive pulmonary disease patients.
AB  - Chronic obstructive pulmonary disease (COPD) is a respiratory disease
      characterized by chronic airflow limitation that leads beyond the pulmonary
      changes to important systemic effects. COPD is characterized by pulmonary and
      systemic inflammation. However, increases in the levels of inflammatory cytokines
      in plasma are found even when the disease is stable. Pulmonary rehabilitation
      improves physical exercise capacity and quality of life and decreases dyspnea.
      The aim of this study was to evaluate whether a home-based pulmonary
      rehabilitation (HBPR) program improves exercise tolerance in COPD patients, as
      well as health-related quality of life and systemic inflammation. This
      prospective study was conducted at the Laboratory of Functional Respiratory
      Evaluation, Nove de Julho University, Sao Paulo, Brazil. After anamnesis,
      patients were subjected to evaluations of health-related quality of life and
      dyspnea, spirometry, respiratory muscle strength, upper limbs incremental test,
      incremental shuttle walk test, and blood test for quantification of systemic
      inflammatory markers (interleukin [IL]-6 and IL-8). At the end of the
      evaluations, patients received a booklet containing the physical exercises to be
      performed at home, three times per week for 8 consecutive weeks. Around 25
      patients were enrolled, and 14 completed the pre- and post-HBPR ratings. There
      was a significant increase in the walked distance and the maximal inspiratory
      pressure, improvements on two components from the health-related quality-of-life
      questionnaire, and a decrease in plasma IL-8 levels after the intervention. The
      HBPR is an important and viable alternative to pulmonary rehabilitation for the
      treatment of patients with COPD; it improves exercise tolerance, inspiratory
      muscle strength, quality of life, and systemic inflammation in COPD patients. 

PMID- 25848242
TI  - COPD and its association with smoking in the Mainland China: a cross-sectional
      analysis of 0.5 million men and women from ten diverse areas.
AB  - PURPOSE: In adult Chinese men, smoking prevalence is high, but little is known
      about its association with chronic respiratory disease, which is still poorly
      diagnosed and managed. METHODS: A nationwide study recruited 0.5 million men and
      women aged 30-79 years during 2004-2008 from ten geographically diverse areas
      across the Mainland China. Information was collected from each participant
      regarding smoking and self-reported physician diagnosis of chronic
      bronchitis/emphysema (CB/E), along with measurement of lung function indices.
      Logistic regression was used to yield sex-specific odds ratios (ORs) relating
      smoking to airflow obstruction (AFO), defined as forced expiratory volume in 1
      second (FEV1)/forced vital capacity (FVC) <0.7 and CB/E, adjusting for age,
      areas, education, and income. RESULTS: Overall 74% of men were ever regular
      smokers; among them, 7.2% had AFO compared with 5.4% in never-smokers, yielding
      an OR of 1.42 (95% confidence interval [CI]: 1.34-1.50). The risk was strongly
      associated with amount smoked and starting to smoke at a younger age. Among ex
      smokers, the OR was more extreme for those who had quit due to illness (OR: 1.86,
      95% CI: 1.77-1.96) than those who had quit by choice (OR:1.08, 95% CI: 1.01
      1.16). CB/E prevalence was also significantly elevated in ex-smokers who had quit
      because of ill health (OR:2.79, 95% CI: 2.64-2.95), but not in regular smokers
      (OR:1.04, 95% CI: 0.96-1.11). Female smokers was rare (3%), but carried an excess
      risk for AFO (OR:1.53, 95% CI: 1.43-1.65) and, to a lesser extent, for CB/E
      (OR:1.28, 95% CI: 1.15-1.42). CONCLUSION: In Mainland China, adult smokers,
      particularly ex-smokers who had quit because of illness, had significantly higher
      prevalence of chronic respiratory disease. AFO appeared to be more strongly
      associated with smoking than self-reported chronic respiratory disease.

PMID- 25848244
TI  - Clinical potential of aclidinium bromide in chronic obstructive pulmonary
      disease.
AB  - Three long-acting muscarinic antagonists (LAMAs) are now available in Europe,
      providing clinicians and patients with a choice of interventions, which is
      important in COPD, which is clinically a heterogeneous disease. The first LAMA,
      tiotropium, has been widely used over the last decade as a once-daily maintenance
      therapy in stable COPD to improve patients' health-related quality of life and to
      reduce the risk of exacerbations. Administered via the HandiHaler((r)) device, it
      is safe and well tolerated. Another new once-daily LAMA, glycopyrronium, has also
      been shown to improve health status and reduce exacerbations, and is well
      tolerated. The subject of this review is a third LAMA, aclidinium bromide, which
      was approved as a twice-daily maintenance bronchodilator treatment. In the
      pivotal Phase III clinical trials, patients receiving aclidinium achieved
      significantly greater improvements in lung function, reductions in
      breathlessness, and improvements in health status compared with placebo, for up
      to 24 weeks. In continuation studies, these improvements were sustained for up to
      52 weeks. Pooled data showed exacerbation frequency was significantly reduced
      with aclidinium versus placebo. Preclinical and pharmacological studies
      demonstrating low systemic bioavailability and a low propensity to induce cardiac
      arrhythmias were translated into a favorable tolerability profile in the clinical
      trial program - the adverse event profile of aclidinium was similar to placebo,
      with a low incidence of anticholinergic and cardiac adverse events. While
      additional studies are needed to evaluate its full clinical potential, aclidinium
      is an important part of this recent expansion of LAMA therapeutic options,
      providing clinicians and patients with an effective and well-tolerated COPD
      treatment. 

PMID- 25848243
TI  - A bibliometric analysis of the 100 most influential papers on COPD.
AB  - OBJECTIVE: We aimed to identify the 100 top-cited articles published on chronic
      obstructive pulmonary disease (COPD) and to analyze their characteristics so as
      to provide information on the achievement and development in COPD research over
      the past decades. METHODS AND MATERIALS: A comprehensive list of citation
      classics in COPD was generated by searching the Science Citation Index expanded
      database, using the keywords "COPD" or "chronic obstructive pulmonary disease" or
      "chronic obstructive pulmonary diseases". The 100 top-cited research papers were
      retrieved by reading the abstract or full text if needed. All eligible articles
      were read for basic information, including country of origin, organizations,
      article type, journals, research field, and authors. RESULTS: The 100 top-cited
      articles on COPD were published between 1966 and 2010. The number of citations
      ranged from 254 to 2,164, with a mean of 450 citations for each article. These
      citation classics were from 32 countries, with 38 from the United States. The
      Imperial College London led the list of classics, with 16 papers. The 100 top
      cited articles were distributed in 18 journals, with the American Journal of
      Respiratory, Critical Care Medicine, and Journal of the American Medical
      Association topping the list. Among the various fields, both respiratory system
      (63%) and general internal medicine (63%) were the most common fields of study
      for the 100 articles. CONCLUSION: Our bibliometric analysis provides a historical
      perspective on the progress of scientific research on COPD. Articles originating
      from the United States and published in high-impact specialized respiratory
      journals are most likely to be cited in the field of COPD research.

PMID- 25848245
TI  - Systemic cytokine signaling via IL-17 in smokers with obstructive pulmonary
      disease: a link to bacterial colonization?
AB  - We examined whether systemic cytokine signaling via interleukin (IL)-17 and
      growth-related oncogene-alpha (GRO-alpha) is impaired in smokers with obstructive
      pulmonary disease including chronic bronchitis (OPD-CB). We also examined how
      this systemic cytokine signaling relates to bacterial colonization in the airways
      of the smokers with OPD-CB. Currently smoking OPD-CB patients (n=60,
      corresponding to Global initiative for chronic Obstructive Lung Disease [GOLD]
      stage I-IV) underwent recurrent blood and sputum sampling over 60 weeks, during
      stable conditions and at exacerbations. We characterized cytokine protein
      concentrations in blood and bacterial growth in sputum. Asymptomatic smokers
      (n=10) and never-smokers (n=10) were included as control groups. During stable
      clinical conditions, the protein concentrations of IL-17 and GRO-alpha were
      markedly lower among OPD-CB patients compared with never-smoker controls, whereas
      the asymptomatic smoker controls displayed intermediate concentrations. Notably,
      among OPD-CB patients, colonization by opportunistic pathogens was associated
      with markedly lower IL-17 and GRO-alpha, compared with colonization by common
      respiratory pathogens or oropharyngeal flora. During exacerbations in the OPD-CB
      patients, GRO-alpha and neutrophil concentrations were increased, whereas protein
      concentrations and messenger RNA for IL-17 were not detectable in a reproducible
      manner. In smokers with OPD-CB, systemic cytokine signaling via IL-17 and GRO
      alpha is impaired and this alteration may be linked to colonization by
      opportunistic pathogens in the airways. Given the potential pathogenic and
      therapeutic implications, these findings deserve to be validated in new and
      larger patient cohorts. 

PMID- 25848246
TI  - Effectiveness of bronchoscopic lung volume reduction using unilateral
      endobronchial valve: a systematic review and meta-analysis.
AB  - BACKGROUND: Bronchoscopic lung volume reduction (BLVR) can be suggested as an
      alternative for surgical lung volume reduction surgery for severe emphysema
      patients. This article intends to evaluate by systematic review the safety and
      effectiveness of BLVR using a one-way endobronchial valve. METHODS: A systematic
      search of electronic databases, including MEDLINE, EMBASE, and the Cochrane
      Library, as well as eight domestic databases up to December 2013, was performed.
      Two reviewers independently screened all references according to selection
      criteria. The Scottish Intercollegiate Guidelines Network criterion was used to
      assess quality of literature. Data from randomized controlled trials were
      combined and meta-analysis was performed. RESULTS: This review included 15
      studies. Forced expiratory volume in 1 second (FEV1) improved in the intervention
      group compared with the control group (mean difference [MD]=6.71, 95% confidence
      interval [CI]: 3.31-10.11). Six-minute walking distance (MD=15.66, 95% CI: 1.69
      29.64) and cycle workload (MD=4.43, 95% CI: 1.80-7.07) also improved. In
      addition, St George's Respiratory Questionnaire score decreased (MD=4.29, 95% CI:
      -6.87 to -1.71) in the intervention group. In a subgroup analysis of patients
      with complete fissure, the FEV1 change from baseline was higher in the BLVR group
      than in the control group for both 6 months (MD=15.28, P<0.001) and 12 months
      (MD=17.65, P<0.001), whereas for patients with incomplete fissure, FEV1 and 6
      minute walking distance showed no change. One-year follow-up randomized
      controlled trials reported deaths, although the cause of death was not related to
      BLVR. Respiratory failure and pneumothorax incidence rates were relatively higher
      in the BLVR group, but the difference was not significant. CONCLUSION: BLVR may
      be an effective and safe procedure for the treatment of severe COPD patients with
      emphysema, based on existing studies.

PMID- 25848247
TI  - Modafinil: a novel alternative to non-invasive ventilation in hypercapnic
      respiratory failure?

PMID- 25848248
TI  - Novel PLGA-based nanoparticles for the oral delivery of insulin.
AB  - BACKGROUND: Insulin is the drug therapy for patients with insulin-dependent
      diabetes mellitus. A number of attempts have been made in the past to overcome
      the problems associated with the oral delivery of insulin, but with little
      success. Orally administered insulin has encountered with many difficulties such
      as rapid degradation and poor intestinal absorption. The potential use of D-alpha
      tocopherol poly(ethylene glycol) 1000 succinate (TPGS)-emulsified poly(ethylene
      glycol) (PEG)-capped poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) was
      investigated for sustained delivery of insulin (IS). OBJECTIVE: To investigate
      the efficacy of TPGS-emulsified PEG-capped PLGA NPs (TPPLG NPs) as a potential
      drug carrier for the oral delivery of insulin. METHODS: A series of biodegradable
      low-molecular-weight PLGA (80/20 [PLG4] and 70/30 [PLG6]) copolymers were
      synthesized by melt polycondensation. The commercial insulin-loaded TPGS
      emulsified PEG-capped PLGA NPs (ISTPPLG NPs) were synthesized by water-oil-water
      emulsion solvent evaporation method. The physical and chemical properties of PLGA
      copolymers, particle size, zeta potential, and morphology of the NPs were
      examined. The in vivo studies of ISTPPLG NPs were carried out in diabetic rats by
      oral administration. RESULTS: The maximum encapsulation efficiency of ISTPPLG6
      NPs was 78.6% +/- 1.2%, and the mean diameter of the NPs was 180 +/- 20 nm. The
      serum glucose level was significantly (twofold) decreased on treatment with
      ISTPPLG NPs, and there was a threefold decrease with insulin-loaded PLGA (70/30)
      NPs when compared to that of free insulin-treated diabetic rats. The results show
      that the oral administration of ISTPPLG6 NPs is an effective method of reducing
      serum glucose level for a period of 24 hours. Histopathological studies reveal
      that ISTPPLG NPs could restore the damage caused by streptozotocin in the liver,
      kidneys, and pancreas, indicating its biocompatibility and regenerative effects.
      CONCLUSION: ISTPPLG6 NPs can act as potential drug carriers for the oral delivery
      of insulin.

PMID- 25848249
TI  - Silica nanoparticles increase human adipose tissue-derived stem cell
      proliferation through ERK1/2 activation.
AB  - BACKGROUND: Silicon dioxide composites have been found to enhance the mechanical
      properties of scaffolds and to support growth of human adipose tissue-derived
      stem cells (hADSCs) both in vitro and in vivo. Silica (silicon dioxide alone)
      exists as differently sized particles when suspended in culture medium, but it is
      not clear whether particle size influences the beneficial effect of silicon
      dioxide on hADSCs. In this study, we examined the effect of different sized
      particles on growth and mitogen-activated protein kinase signaling in hADSCs.
      METHODS: Silica gel was prepared by a chemical reaction using hydrochloric acid
      and sodium silicate, washed, sterilized, and suspended in serum-free culture
      medium for 48 hours, and then sequentially filtered through a 0.22 MUm filter
      (filtrate containing nanoparticles smaller than 220 nm; silica NPs). hADSCs were
      incubated with silica NPs or 3 MUm silica microparticles (MPs), examined by
      transmission electron microscopy, and assayed for cell proliferation, apoptosis,
      and mitogen-activated protein kinase signaling. RESULTS: Eighty-nine percent of
      the silica NPs were around 50-120 nm in size. When hADSCs were treated with the
      study particles, silica NPs were observed in endocytosed vacuoles in the cytosol
      of hADSCs, but silica MPs showed no cell entry. Silica NPs increased the
      proliferation of hADSCs, but silica MPs had no significant effect in this regard.
      Instead, silica MPs induced slight apoptosis. Silica NPs increased
      phosphorylation of extracellular signal-related kinase (ERK)1/2, while silica MPs
      increased phosphorylation of p38. Silica NPs had no effect on phosphorylation of
      Janus kinase or p38. Pretreatment with PD98059, a MEK inhibitor, prevented the
      ERK1/2 phosphorylation and proliferation induced by silica NPs. CONCLUSION:
      Scaffolds containing silicon dioxide for tissue engineering may enhance cell
      growth through ERK1/2 activation only when NPs around 50-120 nm in size are
      included, and single component silica-derived NPs could be useful for
      bioscaffolds in stem cell therapy.

PMID- 25848250
TI  - The fate of calcium carbonate nanoparticles administered by oral route:
      absorption and their interaction with biological matrices.
AB  - BACKGROUND: Orally administered particles rapidly interact with biological fluids
      containing proteins, enzymes, electrolytes, and other biomolecules to eventually
      form particles covered by a corona, and this corona potentially affects particle
      uptake, fate, absorption, distribution, and elimination in vivo. This study
      explored relationships between the biological interactions of calcium carbonate
      particles and their biokinetics. METHODS: We examined the effects of food grade
      calcium carbonates of different particle size (nano [N-Cal] and bulk [B-Cal]:
      specific surface areas of 15.8 and 0.83 m(2)/g, respectively) on biological
      interactions in in vitro simulated physiological fluids, ex vivo biofluids, and
      in vivo in gastrointestinal fluid. Moreover, absorption and tissue distribution
      of calcium carbonates were evaluated following a single dose oral administration
      to rats. RESULTS: N-Cal interacted more with biomatrices than bulk materials in
      vitro and ex vivo, as evidenced by high fluorescence quenching ratios, but it did
      not interact more actively with biomatrices in vivo. Analysis of coronas revealed
      that immunoglobulin, apolipoprotein, thrombin, and fibrinogen, were the major
      corona proteins, regardless of particle size. A biokinetic study revealed that
      orally delivered N-Cal was more rapidly absorbed into the blood stream than B
      Cal, but no significant differences were observed between the two in terms of
      absorption efficiencies or tissue distributions. Both calcium carbonates were
      primarily present as particulate forms in gastrointestinal fluids but enter the
      circulatory system in dissolved Ca(2+), although both types showed partial phase
      transformation to dicalcium phosphate dihydrate. Relatively low dissolution
      (about 4%), no remarkable protein-particle interaction, and the major particulate
      fate of calcium carbonate in vivo gastrointestinal fluids can explain its low
      oral absorption (about 4%) regardless of particle size. CONCLUSION: We conclude
      that calcium carbonate nanoparticles can act more actively with biological
      matrices in vitro and ex vivo, but that in vivo, their biological interactions
      and biokinetics are not affected by particle size.

PMID- 25848251
TI  - Comparison of two self-assembled macromolecular prodrug micelles with different
      conjugate positions of SN38 for enhancing antitumor activity.
AB  - 7-Ethyl-10-hydroxycamptothecin (SN38), an active metabolite of irinotecan (CPT
      11), is a remarkably potent antitumor agent. The clinical application of SN38 has
      been extremely restricted by its insolubility in water. In this study, we
      successfully synthesized two macromolecular prodrugs of SN38 with different
      conjugate positions (chitosan-(C10-OH)SN38 and chitosan-(C20-OH)SN38) to improve
      the water solubility and antitumor activity of SN38. These prodrugs can self
      assemble into micelles in aqueous medium. The particle size, morphology, zeta
      potential, and in vitro drug release of SN38 and its derivatives, as well as
      their cytotoxicity, pharmacokinetics, and in vivo antitumor activity in a
      xenograft BALB/c mouse model were studied. In vitro, chitosan-(C10-OH)SN38 (CS
      (10s)SN38) and chitosan-(C20-OH) SN38 (CS-(20s)SN38) were 13.3- and 25.9-fold
      more potent than CPT-11 in the murine colon adenocarcinoma cell line CT26,
      respectively. The area under the curve (AUC)0-24 of SN38 after intravenously
      administering CS-(10s)SN38 and CS-(20s)SN38 to Sprague Dawley rats was greatly
      improved when compared with CPT-11 (both P<0.01). A larger AUC0-24 of CS
      (20s)SN38 was observed when compared to CS-(10s)SN38 (P<0.05). Both of the novel
      self-assembled chitosan-SN38 prodrugs demonstrated superior anticancer activity
      to CPT-11 in the CT26 xenograft BALB/c mouse model. We have also investigated the
      differences between these macromolecular prodrug micelles with regards to
      enhancing the antitumor activity of SN38. CS-(20s)SN38 exhibited better in vivo
      antitumor activity than CS-(10s)SN38 at a dose of 2.5 mg/kg (P<0.05). In
      conclusion, both macromolecular prodrug micelles improved the in vivo conversion
      rate and antitumor activity of SN38, but the prodrug in which C20-OH was
      conjugated to macromolecular materials could be a more promising platform for
      SN38 delivery. 

PMID- 25848252
TI  - A hybrid substratum for primary hepatocyte culture that enhances hepatic
      functionality with low serum dependency.
AB  - Cell culture systems have proven to be crucial for the in vitro maintenance of
      primary hepatocytes and the preservation of hepatic functional expression at a
      high level. A poly-(N-p-vinylbenzyl-4-O-beta-D-galactopyranosyl-D-gluconamide)
      matrix can recognize cells and promote liver function in a spheroid structure
      because of a specific galactose-asialoglycoprotein receptor interaction.
      Meanwhile, a fusion protein, E-cadherin-Fc, when incubated with various cells,
      has shown an enhancing effect on cellular viability and metabolism. Therefore, a
      hybrid substratum was developed for biomedical applications by using both of
      these materials to combine their advantages for primary hepatocyte cultures. The
      isolated cells showed a monolayer aggregate morphology on the coimmobilized
      surface and displayed higher functional expression than cells on traditional
      matrices. Furthermore, the hybrid system, in which the highest levels of cell
      adhesion and hepatocellular metabolism were achieved with the addition of 1%
      fetal bovine serum, showed a lower serum dependency than the collagen/gelatin
      coated surface. Accordingly, this substrate may attenuate the negative effects of
      serum and further contribute to establishing a defined culture system for primary
      hepatocytes. 

PMID- 25848253
TI  - Water-soluble L-cysteine-coated FePt nanoparticles as dual MRI/CT imaging
      contrast agent for glioma.
AB  - Nanoparticles (NPs) are advantageous for the delivery of diagnosis agents to
      brain tumors. In this study, we attempted to develop an L-cysteine coated FePt
      (FePt-Cys) NP as MRI/CT imaging contrast agent for the diagnosis of malignant
      gliomas. FePt-Cys NPs were synthesized through a co-reduction route, which was
      characterized by transmission electron microscopy, high-resolution transmission
      electron microscopy, powder X-ray diffraction, Fourier transform infrared
      spectroscopy, and dynamic light scattering. The MRI and CT imaging ability of
      FePt-Cys NPs was evaluated using different gliomas cells (C6, SGH44, U251) as the
      model. Furthermore, the biocompatibility of the as-synthesized FePt-Cys NPs was
      evaluated using three different cell lines (ECV304, L929, and HEK293) as the
      model. The results showed that FePt-Cys NPs displayed excellent biocompatibility
      and good MRI/CT imaging ability, thereby indicating promising potential as a dual
      MRI/CT contrast agent for the diagnosis of brain malignant gliomas.

PMID- 25848254
TI  - Chitosan/siRNA functionalized titanium surface via a layer-by-layer approach for
      in vitro sustained gene silencing and osteogenic promotion.
AB  - Titanium surface modification is crucial to improving its bioactivity, mainly its
      bone binding ability in bone implant materials. In order to functionalize
      titanium with small interfering RNA (siRNA) for sustained gene silencing in
      nearby cells, the layer-by-layer (LbL) approach was applied using sodium
      hyaluronate and chitosan/siRNA (CS/siRNA) nanoparticles as polyanion and
      polycation, respectively, to build up the multilayered film on smooth titanium
      surfaces. The CS/siRNA nanoparticle characterization was analyzed first. Dynamic
      contact angle, atomic force microscopy, and scanning electron microscopy were
      used to monitor the layer accumulation. siRNA loaded in the film was quantitated
      and the release profile of film in phosphate-buffered saline was studied. In
      vitro knockdown effect and cytotoxicity evaluation of the film were investigated
      using H1299 human lung carcinoma cells expressing green fluorescent protein
      (GFP). The transfection of human osteoblast-like cell MG63 and H1299 were
      performed and the osteogenic differentiation of MG63 on LbL film was analyzed.
      The CS/siRNA nanoparticles exhibited nice size distribution. During formation of
      the film, the surface wettability, topography, and roughness were alternately
      changed, indicating successful adsorption of the individual layers. The scanning
      electron microscope images clearly demonstrated the hybrid structure between
      CS/siRNA nanoparticles and sodium hyaluronate polymer. The cumulated load of
      siRNA increased linearly with the bilayer number and, more importantly, a gradual
      release of the film allowed the siRNA to be maintained on the titanium surface
      over approximately 1 week. In vitro transfection revealed that the LbL film
      associated siRNA could consistently suppress GFP expression in H1299 without
      showing significant cytotoxicity. The LbL film loading with osteogenic siRNA
      could dramatically increase the osteogenic differentiation in MG63. In
      conclusion, LbL technology can potentially modify titanium surfaces with specific
      gene-regulatory siRNAs to enhance biofunction. 

PMID- 25848255
TI  - Phthalocyanine-loaded graphene nanoplatform for imaging-guided combinatorial
      phototherapy.
AB  - We report a novel cancer-targeted nanomedicine platform for imaging and prospect
      for future treatment of unresected ovarian cancer tumors by intraoperative
      multimodal phototherapy. To develop the required theranostic system, novel low
      oxygen graphene nanosheets were chemically modified with polypropylenimine
      dendrimers loaded with phthalocyanine (Pc) as a photosensitizer. Such a molecular
      design prevents fluorescence quenching of the Pc by graphene nanosheets,
      providing the possibility of fluorescence imaging. Furthermore, the developed
      nanoplatform was conjugated with poly(ethylene glycol), to improve
      biocompatibility, and with luteinizing hormone-releasing hormone (LHRH) peptide,
      for tumor-targeted delivery. Notably, a low-power near-infrared (NIR) irradiation
      of single wavelength was used for both heat generation by the graphene nanosheets
      (photothermal therapy [PTT]) and for reactive oxygen species (ROS)-production by
      Pc (photodynamic therapy [PDT]). The combinatorial phototherapy resulted in an
      enhanced destruction of ovarian cancer cells, with a killing efficacy of 90%-95%
      at low Pc and low-oxygen graphene dosages, presumably conferring cytotoxicity to
      the synergistic effects of generated ROS and mild hyperthermia. An animal study
      confirmed that Pc loaded into the nanoplatform can be employed as a NIR
      fluorescence agent for imaging-guided drug delivery. Hence, the newly developed
      Pc-graphene nanoplatform has the significant potential as an effective NIR
      theranostic probe for imaging and combinatorial phototherapy. 

PMID- 25848256
TI  - Fluoromica nanoparticle cytotoxicity in macrophages decreases with size and
      extent of uptake.
AB  - Polyurethanes are widely used in biomedical devices such as heart valves,
      pacemaker leads, catheters, vascular devices, and surgical dressings because of
      their excellent mechanical properties and good biocompatibility. Layered silicate
      nanoparticles can significantly increase tensile strength and breaking strain of
      polyurethanes potentially increasing the life span of biomedical devices that
      suffer from wear in vivo. However, very little is known about how these
      nanoparticles interact with proteins and cells and how they might exert unwanted
      effects. A series of fluoromica nanoparticles ranging in platelet size from 90 to
      over 600 nm in diameter were generated from the same base material ME100 by high
      energy milling and differential centrifugation. The cytotoxicity of the resulting
      particles was dependent on platelet size but in a manner that is opposite to many
      other types of nanomaterials. For the fluoromicas, the smaller the platelet size,
      the less toxicity was observed. The small fluoromica nanoparticles (<200 nm) were
      internalized by macrophages via scavenger receptors, which was dependent on the
      protein corona formed in serum. This internalization was associated with
      apoptosis in RAW cells but not in dTHP-1 cells. The larger particles were not
      internalized efficiently but mostly decorated the surface of the cells, causing
      membrane disruption, even in the presence of 80% serum. This work suggests the
      smaller fluoromica platelets may be safer for use in humans but their propensity
      to recognize macrophage scavenger receptors also suggests that they will target
      the reticulo-endoplasmic system in vivo. 

PMID- 25848257
TI  - Mechanism of enhanced antiosteoporosis effect of circinal-icaritin by self
      assembled nanomicelles in vivo with suet oil and sodium deoxycholate.
AB  - BACKGROUND: Circinal-icaritin (CIT), one new active aglycone of Epimedium, can
      exert a beneficial effect on osteoporotic bone. However, its low bioavailability
      limits its clinical efficacy for the treatment of osteoporosis. MATERIALS AND
      METHODS: In this paper, suet oil (SO) was used to improve the oral
      bioavailability of CIT and enhance its antiosteoporosis effect and absorption.
      After oral administration of CIT together with SO, the CIT and SO self-assembled
      into nanomicelles under the action of sodium deoxycholate (DOC) by bile
      secretion. The antiosteoporosis effects of the CIT-SO-DOC nanomicelles were
      evaluated in osteoporotic rats by bone mineral density, serum biochemical
      markers, bone microarchitecture, bone biomechanical properties, and related
      protein and gene expressions. We examined the bioavailability of CIT and its
      nanomicelles in vivo, and subsequently the nanomicelles were verified using
      transmission electron microscopy. Finally, we evaluated absorption across a rat
      intestinal perfusion model. RESULTS: Compared with CIT, in the CIT-SO groups,
      protein and messenger ribonucleic acid expressions of osteoprotegerin were
      increased, while expressions of receptor activator of nuclear factor-kappaB
      ligand in bone tissue were decreased; bone-turnover markers in serum of
      hydroxyproline, alkaline phosphatase, tartrate-resistant acid phosphatase 5b, and
      receptor activator of nuclear factor-kappaB ligand levels were decreased, while
      osteoprotegerin and osteocalcin levels were increased; and trabecular bone mass,
      microarchitecture, and bone biomechanical strength were enhanced. The relative
      bioavailabilities of CIT-SO high dosage, CIT-SO medium dosage, and CIT-SO low
      dosage (area under concentration-time curve [AUC]0-infinity) compared with that
      of raw CIT high dosage, CIT medium dosage, and CIT low dosage (AUC0-infinity)
      were 127%, 121%, and 134%, respectively. The average particle size of CIT-DOC was
      significantly decreased after adding SO (P<0.01), and the intestinal permeability
      coefficients of CIT-SO-DOC nanomicelles in the duodenum, jejunum, ileum, and
      colon were all significantly improved (P<0.01). CONCLUSION: The increased
      antiosteoporosis effects and bioavailability of CIT-SO-DOC self-assembled
      nanomicelles were due to an increase in absorption of CIT by reducing the
      particle sizes of CIT. SO may be a practical oral carrier for antiosteoporosis
      drugs with low bioavailability.

PMID- 25848258
TI  - Poloxamer-based binary hydrogels for delivering tramadol hydrochloride: sol-gel
      transition studies, dissolution-release kinetics, in vitro toxicity, and
      pharmacological evaluation.
AB  - In this work, poloxamer (PL)-based binary hydrogels, composed of PL 407 and PL
      188, were studied with regard to the physicochemical aspects of sol-gel
      transition and pharmaceutical formulation issues such as dissolution-release
      profiles. In particular, we evaluated the cytotoxicity, genotoxicity, and in vivo
      pharmacological performance of PL 407 and PL 407-PL 188 hydrogels containing
      tramadol (TR) to analyze its potential treatment of acute pain. Drug-micelle
      interaction studies showed the formation of PL 407-PL 188 binary systems and the
      drug partitioning into the micelles. Characterization of the sol-gel transition
      phase showed an increase on enthalpy variation values that were induced by the
      presence of TR hydrochloride within the PL 407 or PL 407-PL 188 systems. Hydrogel
      dissolution occurred rapidly, with approximately 30%-45% of the gel dissolved,
      reaching ~80%-90% up to 24 hours. For in vitro release assays, formulations
      followed the diffusion Higuchi model and lower K(rel) values were observed for PL
      407 (20%, K(rel) = 112.9 +/- 10.6 MUg . h(-1/2)) and its binary systems PL 407-PL
      188 (25%-5% and 25%-10%, K(rel) =80.8 +/- 6.1 and 103.4 +/- 8.3 MUg . h(-1/2),
      respectively) in relation to TR solution (K(rel) =417.9 +/- 47.5 MUg . h(-1/2),
      P<0.001). In addition, the reduced cytotoxicity (V79 fibroblasts and hepatocytes)
      and genotoxicity (V79 fibroblasts), as well as the prolonged analgesic effects
      (>72 hours) pointed to PL-based hydrogels as a potential treatment, by
      subcutaneous injection, for acute pain.

PMID- 25848259
TI  - Self-nanoemulsifying drug delivery systems ameliorate the oral delivery of
      silymarin in rats with Roux-en-Y gastric bypass surgery.
AB  - Roux-en-Y gastric bypass (RYGB) is a popular surgery to reduce the body weight of
      obese patients. Although food intake is restricted by RYGB, drug absorption is
      also decreased. The purpose of this study was to develop novel self
      nanoemulsifying drug delivery systems (SNEDDS) for enhancing the oral delivery of
      silymarin, which has poor water solubility. The SNEDDS were characterized by
      size, zeta potential, droplet number, and morphology. A technique of RYGB was
      performed in Sprague-Dawley rats. SNEDDS were administered at a silymarin dose of
      600 mg/kg in normal and RYGB rats for comparison with silymarin aqueous
      suspension and polyethylene glycol (PEG) 400 solution. Plasma silibinin, the main
      active ingredient in silymarin, was chosen for estimating the pharmacokinetic
      parameters. SNEDDS diluted in simulated gastric fluid exhibited a droplet size of
      190 nm with a spherical shape. The nanocarriers promoted silibinin availability
      via oral ingestion in RYGB rats by 2.5-fold and 1.5-fold compared to the
      suspension and PEG 400 solution, respectively. A significant double-peak
      concentration of silibinin was detected for RYGB rats receiving SNEDDS.
      Fluorescence imaging showed a deeper and broader penetration of Nile red, the
      fluorescence dye, into the gastrointestinal mucosa from SNEDDS than from PEG 400
      solution. Histological examination showed that SNEDDS caused more minor
      inflammation at the gastrointestinal membrane as compared with that caused by PEG
      400 solution, indicating a shielding of direct silymarin contact with the mucosa
      by the nanodroplets. SNEDDS generally showed low-level or negligible irritation
      in the gastrointestinal tract. Silymarin-loaded SNEDDS were successfully
      developed to improve the dissolution, permeability, and oral bioavailability of
      silymarin. To the best of our knowledge, this is the first investigation
      reporting the usefulness of SNEDDS for improving drug malabsorption elicited by
      gastric bypass surgery. 

PMID- 25848260
TI  - Docetaxel-loaded solid lipid nanoparticles as a basis for a targeted and dose
      sparing personalized breast cancer treatment strategy.

PMID- 25848261
TI  - Nanoscale TiO2 nanotubes govern the biological behavior of human glioma and
      osteosarcoma cells.
AB  - Cells respond to their surroundings through an interactive adhesion process that
      has direct effects on cell proliferation and migration. This research was
      designed to investigate the effects of TiO2 nanotubes with different topographies
      and structures on the biological behavior of cultured cells. The results
      demonstrated that the nanotube diameter, rather than the crystalline structure of
      the coatings, was a major factor for the biological behavior of the cultured
      cells. The optimal diameter of the nanotubes was 20 nm for cell adhesion,
      migration, and proliferation in both glioma and osteosarcoma cells. The
      expression levels of vitronectin and phosphor-focal adhesion kinase were affected
      by the nanotube diameter; therefore, it is proposed that the responses of
      vitronectin and phosphor-focal adhesion kinase to the nanotube could modulate
      cell fate. In addition, the geometry and size of the nanotube coating could
      regulate the degree of expression of acetylated alpha-tubulin, thus indirectly
      modulating cell migration behavior. Moreover, the expression levels of apoptosis
      associated proteins were influenced by the topography. In conclusion, a nanotube
      diameter of 20 nm was the critical threshold that upregulated the expression
      level of Bcl-2 and obviously decreased the expression levels of Bax and caspase
      3. This information will be useful for future biomedical and clinical
      applications. 

PMID- 25848262
TI  - Alendronate-coated long-circulating liposomes containing 99mtechnetium
      ceftizoxime used to identify osteomyelitis.
AB  - Osteomyelitis is a progressive destruction of bones caused by microorganisms.
      Inadequate or absent treatment increases the risk of bone growth inhibition,
      fractures, and sepsis. Among the diagnostic techniques, functional images are the
      most sensitive in detecting osteomyelitis in its early stages. However, these
      techniques do not have adequate specificity. By contrast, radiolabeled
      antibiotics could improve selectivity, since they are specifically recognized by
      the bacteria. The incorporation of these radiopharmaceuticals in drug-delivery
      systems with high affinity for bones could improve the overall uptake. In this
      work, long-circulating and alendronate-coated liposomes containing
      (99m)technetium-radiolabeled ceftizoxime were prepared and their ability to
      identify infectious foci (osteomyelitis) in animal models was evaluated. The
      effect of the presence of PEGylated lipids and surface-attached alendronate was
      evaluated. The bone-targeted long-circulating liposomal (99m)technetium
      ceftizoxime showed higher uptake in regions of septic inflammation than did the
      non-long-circulating and/or alendronate-non-coated liposomes, showing that both
      the presence of PEGylated lipids and alendronate coating are important to
      optimize the bone targeting. Scintigraphic images of septic or aseptic
      inflammation-bearing Wistar rats, as well as healthy rats, were acquired at
      different time intervals after the intravenous administration of these liposomes.
      The target-to-non-target ratio proved to be significantly higher in the
      osteomyelitis-bearing animals for all investigated time intervals.
      Biodistribution studies were also performed after the intravenous administration
      of the formulation in osteomyelitis-bearing animals. A significant amount of
      liposomes were taken up by the organs of the mononuclear phagocyte system (liver
      and spleen). Intense renal excretion was also observed during the entire
      experiment period. Moreover, the liposome uptake by the infectious focus was
      significantly high. These results show that long-circulating and alendronate
      coated liposomes containing (99m)technetium-radiolabeled ceftizoxime have a
      tropism for infectious foci. 

PMID- 25848263
TI  - Graphene-based nanovehicles for photodynamic medical therapy.
AB  - Graphene and its derivatives such as graphene oxide (GO) have been widely
      explored as promising drug delivery vehicles for improved cancer treatment. In
      this review, we focus on their applications in photodynamic therapy. The large
      specific surface area of GO facilitates efficient loading of the photosensitizers
      and biological molecules via various surface functional groups. By incorporation
      of targeting ligands or activatable agents responsive to specific biological
      stimulations, smart nanovehicles are established, enabling tumor-triggering
      release or tumor-selective accumulation of photosensitizer for effective therapy
      with minimum side effects. Graphene-based nanosystems have been shown to improve
      the stability, bioavailability, and photodynamic efficiency of organic
      photosensitizer molecules. They have also been shown to behave as electron sinks
      for enhanced visible-light photodynamic activities. Owing to its intrinsic near
      infrared absorption properties, GO can be designed to combine both photodynamic
      and photothermal hyperthermia for optimum therapeutic efficiency. Critical issues
      and future aspects of photodynamic therapy research are addressed in this review.

PMID- 25848264
TI  - Fabrication of genistein-loaded biodegradable TPGS-b-PCL nanoparticles for
      improved therapeutic effects in cervical cancer cells.
AB  - Genistein is one of the most studied isoflavonoids with potential antitumor
      efficacy, but its poor water solubility limits its clinical application.
      Nanoparticles (NPs), especially biodegradable NPs, entrapping hydrophobic drugs
      have promising applications to improve the water solubility of hydrophobic drugs.
      In this work, TPGS-b-PCL copolymer was synthesized from epsilon-caprolactone
      initiated by d-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) through
      ring-opening polymerization and characterized by Fourier transform infrared
      spectroscopy, proton nuclear magnetic resonance spectroscopy, gel permeation
      chromatography, and thermogravimetric analysis. The genistein-loaded NPs were
      prepared by a modified nanoprecipitation method and characterized in the aspects
      of particle size, surface charge, morphology, drug loading and encapsulation
      efficiency, in vitro drug release, and physical state of the entrapped drug. The
      TPGS-b-PCL NPs were found to have higher cellular uptake efficiency than PCL NPs.
      MTT and colony formation experiments indicated that genistein-loaded TPGS-b-PCL
      NPs achieved the highest level of cytotoxicity and tumor cell growth inhibition
      compared with pristine genistein and genistein-loaded PCL NPs. Furthermore,
      compared with pristine genistein and genistein-loaded PCL NPs, the genistein
      loaded TPGS-b-PCL NPs at the same dose were more effective in inhibiting tumor
      growth in the subcutaneous HeLa xenograft tumor model in BALB/c nude mice. In
      conclusion, the results suggested that genistein-loaded biodegradable TPGS-b-PCL
      nanoparticles could enhance the anticancer effect of genistein both in vitro and
      in vivo, and may serve as a potential candidate in treating cervical cancer. 

PMID- 25848265
TI  - Quantitative analysis of total beta-subunit of human chorionic gonadotropin
      concentration in urine by immunomagnetic reduction to assist in the diagnosis of
      ectopic pregnancy.
AB  - BACKGROUND: The initial diagnosis of ectopic pregnancy depends on physical
      examination, ultrasound, and serial measurements of total beta-subunit of human
      chorionic gonadotropin (hCGbeta) concentrations in serum. The aim of this study
      was to explore the possibility of using quantitative analysis of total hCGbeta in
      urine rather than in serum by immunomagnetic reduction (IMR) assay as an
      alternative method to diagnose an ectopic pregnancy. METHODS: We established a
      standard calibration curve of IMR intensity against total hCGbeta concentration
      based on standard hCGbeta samples, and used an IMR assay to detect total hCGbeta
      concentrations in the urine of pregnant women with lower abdominal pain and/or
      vaginal bleeding. The final diagnosis of ectopic pregnancy was based on
      ultrasound scans, operative findings, and pathology reports. In this prospective
      study, ten clinical samples were used to analyze the relationship of total
      hCGbeta IMR signals between urine and serum. Furthermore, 20 clinical samples
      were used to analyze the relationship between urine IMR signals and serum levels
      of total hCGbeta. RESULTS: The calibration curve extended from 0.01 ng/mL to
      10,000 ng/mL with an excellent correlation (R(2)=0.999). In addition, an
      excellent correlation of total hCGbeta IMR signals between urine and serum was
      noted (R(2)=0.994). Furthermore, a high correlation between urine IMR signals and
      serum levels of total hCGbeta was noted (R(2)=0.862). CONCLUSION: An IMR assay
      can quantitatively analyze total hCGbeta concentrations in urine, and is a
      potential candidate for point-of-care testing to assist in the diagnosis of
      ectopic pregnancy.

PMID- 25848266
TI  - Bypassing the EPR effect with a nanomedicine harboring a sustained-release
      function allows better tumor control.
AB  - The current enhanced permeability and retention (EPR)-based approved
      nanomedicines have had little impact in terms of prolongation of overall survival
      in patients with cancer. For example, the two Phase III trials comparing
      Doxil((r)), the first nanomedicine approved by the US Food and Drug
      Administration, with free doxorubicin did not find an actual translation of the
      EPR effect into a statistically significant increase in overall survival but did
      show less cardiotoxicity. In the current work, we used a two-factor factorial
      experimental design with intraperitoneal versus intravenous delivery and
      nanomedicine versus free drug as factors to test our hypothesis that regional
      (intraperitoneal) delivery of nanomedicine may better increase survival when
      compared with systemic delivery. In this study, we demonstrate that bypassing,
      rather than exploiting, the EPR effect via intraperitoneal delivery of
      nanomedicine harboring a sustained-release function demonstrates dual
      pharmacokinetic advantages, producing more efficient tumor control and
      suppressing the expression of stemness markers, epithelial-mesenchymal
      transition, angiogenesis signals, and multidrug resistance in the tumor
      microenvironment. Metastases to vital organs (eg, lung, liver, and lymphatic
      system) are also better controlled by intraperitoneal delivery of nanomedicine
      than by standard systemic delivery of the corresponding free drug. Moreover, the
      intraperitoneal delivery of nanomedicine has the potential to replace
      hyperthermic intraperitoneal chemotherapy because it shows equal efficacy and
      lower toxicity. In terms of efficacy, exploiting the EPR effect may not be the
      best approach for developing a nanomedicine. Because intraperitoneal chemotherapy
      is a type of regional chemotherapy, the pharmaceutical industry might consider
      the regional delivery of nanomedicine as a valid alternative pathway to develop
      their nanomedicine(s) with the goal of better tumor control in the future. 

PMID- 25848267
TI  - Research highlights from the International Journal of Nanomedicine 2014.

PMID- 25848268
TI  - GEM-loaded magnetic albumin nanospheres modified with cetuximab for simultaneous
      targeting, magnetic resonance imaging, and double-targeted thermochemotherapy of
      pancreatic cancer cells.
AB  - BACKGROUND: Targeted delivery is a promising strategy to improve the diagnostic
      imaging and therapeutic effect of cancers. In this paper, novel cetuximab (C225)
      conjugated, gemcitabine (GEM)-containing magnetic albumin nanospheres (C225
      GEM/MANs) were fabricated and applied as a theranostic nanocarrier to conduct
      simultaneous targeting, magnetic resonance imaging (MRI), and double-targeted
      thermochemotherapy against pancreatic cancer cells. METHODS: Fe3O4 nanoparticles
      (NPs) and GEM co-loaded albumin nanospheres (GEM/MANs) were prepared, and then
      C225 was further conjugated to synthesize C225-GEM/MANs. Their morphology, mean
      particle size, GEM encapsulation ratio, specific cell-binding ability, and
      thermal dynamic profiles were characterized. The effects of discriminating
      different EGFR-expressing pancreatic cancer cells (AsPC-1 and MIA PaCa-2) and
      monitoring cellular targeting effects were assessed by targeted MRI. Lastly, the
      antitumor efficiency of double/C225/magnetic-targeted and nontargeted
      thermochemotherapy was compared with chemotherapy alone using 3-(4, 5-dimethyl-2
      thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and flow cytometry (FCM)
      assay. RESULTS: When treated with targeted nanospheres, AsPC-1 cells showed a
      significantly less intense MRI T2 signal than MIA PaCa-2 cells, while both cells
      had similar signal strength when incubated with nontargeted nanospheres. T2
      signal intensity was significantly lower when magnetic and C225 targeting were
      combined, rather than used alone. The inhibitory and apoptotic rates of each
      thermochemotherapy group were significantly higher than those of the chemotherapy
      alone groups. Additionally, both MTT and FCM analysis verified that double
      targeted thermochemotherapy had the highest targeted killing efficiency among all
      groups. CONCLUSION: The C225-GEM/MANs can distinguish various EGFR-expressing
      live pancreatic cancer cells, monitor diverse cellular targeting effects using
      targeted MRI imaging, and efficiently mediate double-targeted thermochemotherapy
      against pancreatic cancer cells.

PMID- 25848269
TI  - Elucidating the in vivo fate of nanocrystals using a physiologically based
      pharmacokinetic model: a case study with the anticancer agent SNX-2112.
AB  - INTRODUCTION: SNX-2112 is a promising anticancer agent but has poor solubility in
      both water and oil. In the study reported here, we aimed to develop a nanocrystal
      formulation for SNX-2112 and to determine the pharmacokinetic behaviors of the
      prepared nanocrystals. METHODS: Nanocrystals of SNX-2112 were prepared using the
      wet-media milling technique and characterized by particle size, differential
      scanning calorimetry, drug release, etc. Physiologically based pharmacokinetic
      (PBPK) modeling was undertaken to evaluate the drug's disposition in rats
      following administration of drug cosolvent or nanocrystals. RESULTS: The
      optimized SNX-2112 nanocrystals (with poloxamer 188 as the stabilizer) were 203
      nm in size with a zeta potential of -11.6 mV. In addition, the nanocrystals
      showed a comparable release profile to the control (drug cosolvent). Further, the
      rat PBPK model incorporating the parameters of particulate uptake (into the liver
      and spleen) and of in vivo drug release was well fitted to the experimental data
      following administration of the drug nanocrystals. The results reveal that the
      nanocrystals rapidly released drug molecules in vivo, accounting for their
      cosolvent-like pharmacokinetic behaviors. Due to particulate uptake, drug
      accumulation in the liver and spleen was significant at the initial time points
      (within 1 hour). CONCLUSION: The nanocrystals should be a good choice for the
      systemic delivery of the poorly soluble drug SNX-2112. Also, our study
      contributes to an improved understanding of the in vivo fate of nanocrystals.

PMID- 25848270
TI  - Poly(lactic-co-glycolic acid) nanoparticles conjugated with CD133 aptamers for
      targeted salinomycin delivery to CD133+ osteosarcoma cancer stem cells.
AB  - BACKGROUND: Cancer stem cells (CSCs) possess the characteristics associated with
      normal stem cells and are responsible for cancer initiation, recurrence, and
      metastasis. CD133 is regarded as a CSCs marker of osteosarcoma, which is the most
      common primary bone malignancy in childhood and adolescence. Salinomycin, a
      polyether ionophore antibiotic, has been shown to kill various CSCs, including
      osteosarcoma CSCs. However, salinomycin displayed poor aqueous solubility that
      hinders its clinical application. The objective of this study was to develop
      salinomycin-loaded nanoparticles to eliminate CD133(+) osteosarcoma CSCs.
      METHODS: The salinomycin-loaded PEGylated poly(lactic-co-glycolic acid)
      nanoparticles (SAL-NP) conjugated with CD133 aptamers (Ap-SAL-NP) were developed
      by an emulsion/solvent evaporation method, and the targeting and cytotoxicity of
      Ap-SAL-NP to CD133(+) osteosarcoma CSCs were evaluated. RESULTS: The
      nanoparticles are of desired particle size (~150 nm), drug encapsulation
      efficiency (~50%), and drug release profile. After 48 hours treatment of the Saos
      2 CD133(+) osteosarcoma cells with drugs formulated in Ap-SAL-NP, SAL-NP, and
      salinomycin, the concentrations needed to kill 50% of the incubated cells were
      found to be 2.18, 10.72, and 5.07 MUg/mL, respectively, suggesting that Ap-SAL-NP
      could be 4.92 or 2.33 fold more effective than SAL-NP or salinomycin,
      respectively. In contrast, Ap-SAL-NP was as effective as SAL-NP, and less
      effective than salinomycin in Saos-2 CD133(-) cells, suggesting that Ap-SAL-NP
      possess specific cytotoxicity toward Saos-2 CD133(+) cells. Ap-SAL-NP showed the
      best therapeutic effect in Saos-2 osteosarcoma xenograft mice, compared with SAL
      NP or salinomycin. Significantly, Ap-SAL-NP could selectively kill CD133(+)
      osteosarcoma CSCs both in vitro and in vivo, as reflected by the tumorsphere
      formation and proportion of Saos-2 CD133(+) cells. CONCLUSION: Our results
      suggest that CD133 is a potential target for drug delivery to osteosarcoma CSCs
      and that it is possible to significantly inhibit the osteosarcoma growth by
      killing CD133(+) osteosarcoma CSCs. We demonstrated that Ap-SAL-NP have the
      potential to target and kill CD133(+) osteosarcoma CSCs.

PMID- 25848271
TI  - Angiogenesis and bone regeneration of porous nano-hydroxyapatite/coralline blocks
      coated with rhVEGF165 in critical-size alveolar bone defects in vivo.
AB  - To improve the regenerative performance of nano-hydroxyapatite/coralline
      (nHA/coral) block grafting in a canine mandibular critical-size defect model,
      nHA/coral blocks were coated with recombinant human vascular endothelial growth
      factor(165) (rhVEGF) via physical adsorption (3 MUg rhVEGF165 per nHA/coral
      block). After the nHA/coral blocks and VEGF/nHA/coral blocks were randomly
      implanted into the mandibular box-shaped defects in a split-mouth design, the
      healing process was evaluated by histological observation and histomorphometric
      and immunohistological analyses. The histological evaluations revealed the
      ingrowth of newly formed blood vessels and bone at the periphery and cores of the
      blocks in both groups at both 3 and 8 weeks postsurgery, respectively. In the
      histomorphometric analysis, the VEGF/nHA/coral group exhibited a larger quantity
      of new bone formation at 3 and 8 weeks postsurgery. The percentages of newly
      formed bone within the entire blocks in the VEGF/nHA/coral group were 27.3% +/-
      8.1% and 39.3% +/- 12.8% at 3 weeks and 8 weeks, respectively, and these values
      were slightly greater than those of the nHA/coral group (21.7% +/- 3.0% and 32.6%
      +/- 10.3%, respectively), but the differences were not significant (P>0.05). The
      immunohistological evaluations revealed that the neovascular density in the
      VEGF/nHA/coral group (146 +/- 32.9 vessel/mm(2)) was much greater than that in
      the nHA/coral group (105 +/- 51.8 vessel/mm(2)) at the 3-week time point
      (P<0.05), but no significant difference was observed at the 8-week time point
      (341 +/- 86.1 and 269 +/- 50.7 vessel/mm(2), respectively, P>0.05). The present
      study indicated that nHA/coral blocks might be optimal scaffolds for block
      grafting in critical-size mandibular defects and that additional VEGF coating via
      physical adsorption can promote angiogenesis in the early stage of bone healing,
      which suggests that prevascularized nHA/coral blocks have significant potential
      as a bioactive material for bone regeneration in large-scale alveolar defects.

PMID- 25848272
TI  - Biosynthesis, characterization, and antimicrobial applications of silver
      nanoparticles.
AB  - In the present study, the strain Brevibacterium frigoritolerans DC2 was explored
      for the efficient and extracellular synthesis of silver nanoparticles. These
      biosynthesized silver nanoparticles were characterized by ultraviolet-visible
      spectrophotometry, which detected the formation of silver nanoparticles in the
      reaction mixture and showed a maximum absorbance at 420 nm. In addition, field
      emission transmission electron microscopy revealed the spherical shape of the
      nanoparticles. The dynamic light scattering results indicated the average
      particle size of the product was 97 nm with a 0.191 polydispersity index.
      Furthermore, the product was analyzed by energy dispersive X-ray spectroscopy, X
      ray diffraction, and elemental mapping, which displayed the presence of elemental
      silver in the product. Moreover, on a medical platform, the product was checked
      against pathogenic microorganisms including Vibrio parahaemolyticus, Salmonella
      enterica, Bacillus anthracis, Bacillus cereus, Escherichia coli, and Candida
      albicans. The nanoparticles demonstrated antimicrobial activity against all of
      these pathogenic microorganisms. Additionally, the silver nanoparticles were
      evaluated for their combined effects with the commercial antibiotics lincomycin,
      oleandomycin, vancomycin, novobiocin, penicillin G, and rifampicin against these
      pathogenic microorganisms. These results indicated that the combination of
      antibiotics with biosynthesized silver nanoparticles enhanced the antimicrobial
      effects of antibiotics. Therefore, the current study is a demonstration of an
      efficient biological synthesis of silver nanoparticles by B. frigoritolerans DC2
      and its effect on the enhancement of the antimicrobial efficacy of well-known
      commercial antibiotics.

PMID- 25848273
TI  - Highly effective antiangiogenesis via magnetic mesoporous silica-based siRNA
      vehicle targeting the VEGF gene for orthotopic ovarian cancer therapy.
AB  - Therapeutic antiangiogenesis strategies have demonstrated significant antitumor
      efficacy in ovarian cancer. Recently, RNA interference (RNAi) has come to be
      regarded as a promising technology for treatment of disease, especially cancer.
      In this study, vascular endothelial growth factor (VEGF)-small interfering RNA
      (siRNA) was encapsulated into a magnetic mesoporous silica nanoparticle (M-MSN)
      based, polyethylenimine (PEI)-capped, polyethylene glycol (PEG)-grafted,
      fusogenic peptide (KALA)-functionalized siRNA delivery system, termed M-MSN_VEGF
      siRNA@PEI-PEG-KALA, which showed significant effectiveness with regard to VEGF
      gene silencing in vitro and in vivo. The prepared siRNA delivery system readily
      exhibited cellular internalization and ease of endosomal escape, resulting in
      excellent RNAi efficacy without associated cytotoxicity in SKOV3 cells. In in
      vivo experiments, notable retardation of tumor growth was observed in orthotopic
      ovarian tumor-bearing mice, which was attributed to significant inhibition of
      angiogenesis by systemic administration of this nanocarrier. No obvious toxic
      drug responses were detected in major organs. Further, the magnetic core of M
      MSN_VEGF siRNA@PEI-PEG-KALA proved capable of probing the site and size of the
      ovarian cancer in mice on magnetic resonance imaging. Collectively, the results
      demonstrate that an M-MSN-based delivery system has potential to serve as a
      carrier of siRNA therapeutics in ovarian cancer. 

PMID- 25848274
TI  - Decisional impairments in cocaine addiction, reward bias, and cortical
      oscillation "unbalance".
AB  - A vast amount of research has suggested that subjects with substance use disorder
      (SUD) might have difficulty making advantageous decisions that opt in favor of a
      longer-term, larger reward than an immediate, smaller reward. The current
      research explored the impact of reward bias and cortical frontal asymmetry (left
      lateralization effect) in SUD in response to a decisional task (Iowa Gambling
      Task). Fifty SUD participants and 40 controls (CG) were tested using the Iowa
      Gambling Task. Electrophysiology (electroencephalography) recording was performed
      during task execution. We measured left and right dorsolateral prefrontal cortex
      power activity. Behavioral responses (gain/loss options); frequency band
      modulation (asymmetry index) for delta, theta, alpha, and beta band; and cortical
      source localization (standardized low-resolution brain electromagnetic
      tomography) were considered. The SUD group opted in favor of the immediate reward
      option (loss) more frequently than the long-term option (gain) when compared to
      the CG. Secondly, SUD showed increased left-hemisphere activation in response to
      losing (with immediate reward) choices in comparison with the CG. The left
      hemispheric unbalance effect and the "reward bias" were adduced to explain the
      decisional impairment in SUD. 

PMID- 25848275
TI  - Predictors of premature discontinuation of outpatient treatment after discharge
      of patients with posttraumatic stress disorder.
AB  - OBJECTIVE: This study aimed to examine the sociodemographic and disease-related
      variables associated with the premature discontinuation of psychiatric outpatient
      treatment after discharge among patients with noncombat-related posttraumatic
      stress disorder. METHODS: We retrospectively reviewed the medical records of
      patients who were discharged with a diagnosis of posttraumatic stress disorder.
      RESULTS: Fifty-five percent of subjects (57/104) prematurely discontinued
      outpatient treatment within 6 months of discharge. Comparing sociodemographic
      variables between the 6-month non-follow-up group and 6-month follow-up group,
      there were no variables that differed between the two groups. However, comparing
      disease-related variables, the 6-month follow-up group showed a longer
      hospitalization duration and higher Global Assessment of Function score at
      discharge. The logistic regression analysis showed that a shorter duration of
      hospitalization predicted premature discontinuation of outpatient treatment
      within 6 months of discharge. CONCLUSION: The duration of psychiatric
      hospitalization for posttraumatic stress disorder appeared to influence the
      premature discontinuation of outpatient treatment after discharge.

PMID- 25848276
TI  - Forehead carbuncle with intractable headache.
AB  - Although carbuncles are commonly seen and may heal on their own or respond well
      to treatment, in rare conditions, bacteria from carbuncles can spread into the
      bloodstream and migrate to other areas of the body. Herein, we report on an
      elderly female who suffered from forehead carbuncle with intractable headache,
      later confirmed as having subgaleal abscess. Physicians should pay special
      attention to elderly and immune-compromised patients with carbuncles located on
      the middle of the face, especially when accompanied by intractable headache, to
      avoid poor outcome. 

PMID- 25848277
TI  - Prevalence and correlates of attention-deficit hyperactivity disorder symptoms in
      Korean college students.
AB  - BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) persists into
      adulthood in a high proportion of cases, causing social difficulties and
      affective problems. We evaluated the prevalence of symptoms of ADHD and the
      correlates thereof in Korean college students. METHODS: A total of 2,172 college
      students, stratified to reflect geographical differences, were asked to complete
      self-report questionnaires on ADHD symptoms, depression, and related factors.
      RESULTS: ADHD symptoms were found in 7.6% of college students. Univariate
      analysis revealed that younger students had higher rates of ADHD symptoms than
      did older students. We found significant associations between ADHD symptoms and
      problematic alcohol use, depression, and lifetime suicidal behavior. Multivariate
      analysis revealed that ADHD symptoms in adults were significantly associated with
      depression (odds ratio [OR] =4.69; 95% confidence interval [CI] 3.23-6.80;
      P<0.001) and overweight or obesity (OR =1.50; 95% CI 1.02-2.22; P=0.040), after
      controlling for sex and age. CONCLUSION: These results have implications in terms
      of the mental health interventions required to assess problems such as
      depression, alcohol use, obesity, and suicidality in young adults with ADHD
      symptoms.

PMID- 25848278
TI  - Physical activity as a protective factor against depressive symptoms in older
      Chinese veterans in the community: result from a national cross-sectional study.
AB  - BACKGROUND: Physical activity is generally considered to be effective in reducing
      the prevalence of depression and promoting remission of its symptoms. However,
      large-scale epidemiological research on this issue is lacking in older Chinese
      adults. We performed a nationwide epidemiological survey to determine the
      relationship between physical activity and depressive symptoms in older Chinese
      veterans in the community, with adjustment for potential confounders. METHODS: A
      cross-sectional study was conducted in a representative sample of 9,676 community
      dwelling older Chinese veterans. Depressive symptoms were identified using the
      Center for Epidemiological Studies Depression Scale. Physical activity was self
      reported using a one-year physical activity questionnaire. Information about
      covariates was obtained by questionnaire-based interview. Relationships between
      study variables and symptoms of depression were estimated using unadjusted and
      adjusted analyses. RESULTS: The median age was 82.29 (interquartile range 80.25
      84.60) years. In total, 81.84% of the study participants engaged in physical
      activity that was predominantly light in intensity. In unadjusted analyses,
      physical activity was associated with a significantly decreased likelihood of
      depressive symptoms (5.43% versus 18.83%, P<0.0001). Multivariate logistic
      regression with adjustment and controlling for confounders, physical activity was
      still inversely associated with depressive symptoms and was the only independent
      protective factor (odds ratio 0.57, 95% confidence interval 0.44-0.72, P<0.0001)
      among the associated factors in this study. In a univariate general linear model,
      there was a significant difference in Center for Epidemiological Studies
      Depression Scale score between subjects participating in active physical activity
      and those who did not (F=59.07, P<0.0001). CONCLUSION: This study found an
      inverse relationship between physical activity and symptoms of depression in
      older Chinese veterans in the community. It was also indicated that the
      antidepressant effect of physical activity probably extended to the oldest-old,
      and the light-intensity physical activity was probably available for the same
      protective effect. This information could be used to devise further interventions
      to prevent or ameliorate symptoms of depression.

PMID- 25848279
TI  - Neurofibromatosis type 1 and attention deficit hyperactivity disorder: a case
      study and literature review.
AB  - BACKGROUND: The cognitive profile of children with neurofibromatosis type 1 (NF1)
      and attention deficit hyperactivity disorder (ADHD) has been well characterized,
      but few studies have evaluated the cognitive abilities of adults with NF1 and
      ADHD. OBJECTIVES: We investigated 1) the cognitive profile of an adult patient
      with NF1 and inattention problems, 2) changes in his cognition after 14 months of
      follow-up, and 3) whether the patient exhibited comorbid NF1 and ADHD or
      secondary ADHD-like symptoms. METHODS: We administered neuropsychological tests
      of executive function, attention, verbal and visual memory, visuospatial
      function, and language during two evaluations separated by 14 months. RESULTS: We
      found no changes in sustained attention, language, or verbal memory. Visual
      memory, verbal learning, selective attention inhibitory control, and problem
      solving declined over time, whereas visual search, psychomotor speed,
      visuospatial function, and mental flexibility improved. CONCLUSION: Our patient
      exhibited a cognitive profile characteristic of both NF1 and ADHD, leading to the
      hypothesis that the patient had comorbid ADHD instead of secondary ADHD-like
      symptoms. More studies are necessary to characterize the cognition of patients
      with NF1 and ADHD.

PMID- 25848280
TI  - Association of metabotropic glutamate receptor 3 gene polymorphisms with
      schizophrenia risk: evidence from a meta-analysis.
AB  - To date, the role of metabotropic glutamate receptor 3 (GRM3) rs274622,
      rs1468412, rs917071, rs6465084, and rs2299225 polymorphisms in schizophrenia
      remains controversial. To provide a clearer picture for the effect of the five
      most studied GRM3 polymorphisms on risk of schizophrenia, this meta-analysis with
      eligible data from published studies was performed. Relevant case-control studies
      were retrieved by literature search and selected according to established
      inclusion criteria. Odds ratios with 95% confidence intervals were used to assess
      the strength of association. A total of 33 individual studies were identified and
      included in our meta-analysis: nine for rs1468412, with 5,314 cases and 6,147
      controls; six for rs917071, with 2,660 cases and 3,517 controls; seven for
      rs274622, with 3,820 cases and 4,015 controls; five for rs2299225, with 3,492
      cases and 3,735 controls; and six for rs6465084, with 4,960 cases and 5,613
      controls. However, no significant association was found between these GRM3
      polymorphisms and schizophrenia in the overall population. With respect to
      rs1468412 polymorphism, a finding of very borderline statistical significance
      emerged in dominant comparison model for non-Asian populations, calling for large
      scale verification to assess the marginally elevated risk of schizophrenia. In
      conclusion, these GRM3 polymorphisms have limited effect on the risks of
      schizophrenia. Further large and well-designed studies are needed to confirm this
      conclusion. 

PMID- 25848281
TI  - Effects of prolonged head-down bed rest on working memory.
AB  - BACKGROUND: The weightlessness caused by prolonged bed rest results in changes in
      cerebral circulation and thus, brain functions, which is of interest. METHODS: We
      investigated the effects of 45-day, -6 degrees  head-down bed rest, which
      stimulated microgravity, on working memory in 16 healthy male participants. The 2
      back task was used to test the working memory variations on the 2nd day before
      bed rest (R-2); on the 11th (R11), 20th (R20), 32nd (R32), and 40th (R40) days of
      bed rest; and on the eighth day after bed rest (R+8). The cognitive response and
      the physiological reactivity (such as galvanic skin response, heart rate, and
      heart rate variability) under the 2-back task were recorded simultaneously.
      RESULTS: The results showed that compared with R-2, on the R+8, the participants'
      galvanic skin response increased significantly, and the high frequency of heart
      rate variability (HF), low frequency of heart rate variability (LF), and reaction
      time in the 2-back task decreased significantly. There were positive correlations
      between the participants' reaction time of working memory and the LF/HF under
      head-down bed rest (at R11, R20, and R32). CONCLUSION: The results suggested that
      the prolonged head-down bed rest may have a detrimental effect on individual
      physiology and working memory. Physiology indices, such as galvanic skin response
      and heart rate variability, were sensitive to the prolonged bed rest.

PMID- 25848282
TI  - Different presence of Chlamydia pneumoniae, herpes simplex virus type 1, human
      herpes virus 6, and Toxoplasma gondii in schizophrenia: meta-analysis and
      analytical study.
AB  - In the present study we have performed both a meta-analysis and an analytical
      study exploring the presence of Chlamydia pneumoniae, herpes simplex virus type
      1, human herpes virus 6, and Toxoplasma gondii antibodies in a sample of 143
      schizophrenic patients and 143 control subjects. The meta-analysis was performed
      on papers published up to April 2014. The presence of serum immunoglobulin G and
      immunoglobulin A was performed by enzyme-linked immunosorbent assay test. The
      detection of microbial DNA in total peripheral blood was performed by nested
      polymerase chain reaction. The meta-analysis showed that: 1) C. pneumoniae DNA in
      blood and brain are more common in schizophrenic patients; 2) there is
      association with parasitism by T. gondii, despite the existence of publication
      bias; and 3) herpes viruses were not more common in schizophrenic patients. In
      our sample only anti-Toxoplasma immunoglobulin G was more prevalent and may be a
      risk factor related to schizophrenia, with potential value for prevention. 

PMID- 25848284
TI  - Erratum: Effects of switching from olanzapine to aripiprazole on the metabolic
      profiles of patients with schizophrenia and metabolic syndrome: a double-blind,
      randomized, open-label study [Corrigendum].
AB  - [This corrects the article on p. 685 in vol. 11, PMID: 25792838.]. 

PMID- 25848283
TI  - Patients with schizophrenia or schizoaffective disorder who receive multiple
      electroconvulsive therapy sessions: characteristics, indications, and results.
AB  - BACKGROUND: While electroconvulsive therapy (ECT) has been used for many years,
      there is insufficient research regarding the indications for
      continuation/maintenance (C/M)-ECT, its safety and efficacy, and the
      characteristics of patients with schizophrenia or schizoaffective disorder who
      receive multiple ECT sessions. The aims of this study were to characterize a
      series of patients who received 30 ECT sessions or more, to describe treatment
      regimens in actual practice, and to examine the results of C/M-ECT in terms of
      safety and efficacy, especially the effect on aggression and functioning.
      METHODS: We performed a retrospective chart review of 20 consecutive patients
      (mean age 64.6 years) with schizophrenia (n=16) or schizoaffective disorder (n=4)
      who received at least 30 ECT sessions at our ECT unit, and also interviewed the
      treating physician and filled out the Clinical Global Impression-Severity, Global
      Assessment of Functioning, and the Staff Observation Aggression Scale-Revised.
      RESULTS: Patients received a mean of 91.3 ECT sessions at a mean interval of 2.6
      weeks. All had been hospitalized for most or all of the previous 3 years. There
      were no major adverse effects, and cognitive side effects were relatively minimal
      (cognitive deficit present for several hours after treatment). We found that ECT
      significantly reduced scores on the Staff Observation Aggression Scale-Revised
      subscales for verbal aggression and self-harm, and improved Global Assessment of
      Functioning scores. There were reductions in total aggression scores, subscale
      scores for harm to objects and to others, and Clinical Global Impression-Severity
      scores, these were not statistically significant. CONCLUSION: C/M-ECT is safe and
      effective for chronically hospitalized patients. It improves general functioning
      and reduces verbal aggression and self-harm. More research using other aggression
      tools is needed to determine its effects and to reproduce our findings in
      prospective and controlled studies.

PMID- 25848285
TI  - Decreased serum levels of brain-derived neurotrophic factor in schizophrenic
      patients with deficit syndrome.
AB  - BACKGROUND: Brain-derived neurotrophic factor (BDNF) is a well-established
      neurotrophin that plays a role in the pathophysiology of numerous psychiatric
      disorders. Many studies have investigated the serum BDNF levels in patients with
      schizophrenia. However, there are restricted data in the literature that compare
      the serum BDNF levels in patients with deficit and nondeficit syndromes. In this
      study, we aimed to compare the serum BDNF levels between schizophrenic patients
      with deficit or nondeficit syndrome and healthy controls. METHODS: After
      fulfilling the inclusion and exclusion criteria, 58 patients with schizophrenia
      and 36 healthy controls were included in the study. The patients were grouped as
      deficit syndrome (N=23) and nondeficit syndrome (N=35) according to the Schedule
      for the Deficit Syndrome. Three groups were compared in terms of the
      sociodemographic and clinical variants and serum BDNF levels. RESULTS: The groups
      were similar in terms of age, sex, body mass index, and smoking status. The serum
      BDNF levels in patients with deficit syndrome were significantly lower than those
      in healthy controls. In contrast, the serum BDNF levels in patients with
      nondeficit syndrome were similar to those in healthy controls. CONCLUSION: This
      study suggests that decreased BDNF levels may play a role in the pathophysiology
      of schizophrenic patients with deficit syndrome. Nonetheless, additional studies
      using a larger patient sample size are needed to investigate the serum BDNF
      levels in schizophrenic patients with deficit syndrome.

PMID- 25848286
TI  - Aripiprazole-associated tic in a schizophrenia patient.
AB  - Tic disorder, characterized by the presence of both motor and vocal tics is
      common in adolescents and adults. Antipsychotics including typical antipsychotics
      and atypical antipsychotics are generally recognized by experts as the most
      effective pharmacological treatment for tics. However, previous studies suggest
      that tic-like symptoms might manifest during treatment with atypical
      antipsychotics such as clozapine, quetiapine, but not aripiprazole. We present
      the first case, to our knowledge, of an adult schizophrenia patient who developed
      tics during treatment with aripiprazole. 

PMID- 25848288
TI  - High prevalence of sleep and mood disorders in dry eye patients: survey of 1,000
      eye clinic visitors.
AB  - PURPOSE: We aimed to explore the prevalence of probable sleep and mood disorders
      in eye clinic visitors. METHODS: This was a cross-sectional study. The
      participants were outpatients at six eye clinics from January through March,
      2014. Outpatients were invited to complete a questionnaire containing the
      Pittsburgh Sleep Quality Index (PSQI) and Hospital Anxiety and Depression Scale
      (HADS). A final diagnosis was made, and patients were classified into six
      diagnostic groups. The main outcome measures were the scores of the PSQI and HADS
      among the diagnostic groups. RESULTS: A total 1,000 outpatients participated, and
      730 patients (mean age 59.5+/-19.0 years; 487 females) were analyzed after
      exclusion of children and patients diagnosed with healthy eyes, acute injury, or
      unilateral pseudophakia. The mean PSQI and HADS scores across all patients were
      5.3+/-3.1 and 9.2+/-6.2, respectively. For the diagnostic groups, the mean PSQI
      and HADS scores, respectively, were 5.7+/-3.3 and 10.2+/-6.0 for dry eye (n=247),
      5.4+/-3.2 and 9.2+/-5.7 for bilateral cataracts (n=159), 5.3+/-3.3 and 8.0+/-5.3
      for bilateral pseudophakia (n=99), and, 5.0+/-3.1 and 9.8+/-6.6 for glaucoma
      (n=109). Overall, 37.3% of patients were poor sleepers (PSQI >=6), and 45.5% had
      possible mood disorders (HADS >=10). Stepwise regression analysis revealed that
      the PSQI and HADS scores were significantly correlated with both age (P<0.05) and
      the presence of dry eye (P<0.05). CONCLUSION: The prevalence of sleep and mood
      disorders was significantly higher in patients with dry eye. The present results
      suggest consultation-liaison psychiatry services may be beneficial among eye
      disease patients.

PMID- 25848289
TI  - Erratum: A cross-sectional study on perception of stigma by Chinese schizophrenia
      patients [Retraction].
AB  - After many attempts over an extended period we were advised by the authors that
      they were unable to provide access to the underlying data. As a result we have
      been unable to assuage our serious concerns about the accuracy of the statistical
      analyses and Drs Pinder and Tang have decided to retract this paper.

PMID- 25848287
TI  - Major depressive disorder: mechanism-based prescribing for personalized medicine.
AB  - Individual patients with depression present with unique symptom clusters -
      before, during, and even after treatment. The prevalence of persistent,
      unresolved symptoms and their contribution to patient functioning and disease
      progression emphasize the importance of finding the right treatment choice at the
      onset and the utility of switching medications based on suboptimal responses. Our
      primary goal as clinicians is to improve patient function and quality of life. In
      fact, feelings of well-being and the return to premorbid levels of functioning
      are frequently rated by patients as being more important than symptom relief.
      However, functional improvements often lag behind resolution of mood, attributed
      in large part to persistent and functionally impairing symptoms - namely,
      fatigue, sleep/wake disturbance, and cognitive dysfunction. Thus, patient
      outcomes can be optimized by deconstructing each patient's depressive profile to
      its component symptoms and specifically targeting those domains that
      differentially limit patient function. This article will provide an evidence
      based framework within which clinicians may tailor pharmacotherapy to patient
      symptomatology for improved treatment outcomes. 

PMID- 25848292
TI  - Ranolazine versus placebo in patients with ischemic cardiomyopathy and persistent
      chest pain or dyspnea despite optimal medical and revascularization therapy:
      randomized, double-blind crossover pilot study.
AB  - BACKGROUND: Patients with ischemic cardiomyopathy (ICM) may continue to
      experience persistent chest pain and/or dyspnea despite pharmacologic therapy and
      revascularization. We hypothesized that ranolazine would reduce anginal symptoms
      or dyspnea in optimally treated ICM patients. METHODS: In this randomized, double
      blind, crossover-design pilot study, 28 patients with ICM (ejection fraction less
      or equal 40%) were included after providing informed consent. A total of 24
      patients completed both placebo and ranolazine treatments and were analyzed. All
      patients were on treatment with a beta blocker, an angiotensin-converting enzyme
      inhibitor (or angiotensin receptor blocker), and at least one additional
      antianginal drug. After randomization, patients received up to 1,000 mg
      ranolazine orally twice a day, as tolerated, versus placebo. The primary end
      point was change in angina as assessed by the Seattle Angina Questionnaire (SAQ),
      or in dyspnea as assessed by the Rose Dyspnea Scale (RDS). Change in the RDS and
      SAQ score from baseline was compared, for ranolazine and placebo, using the
      Wilcoxon signed rank test or paired t-test. RESULTS: Patients had the following
      demographic and clinical variables: mean age of 71.5 years; male (82.1%); prior
      coronary bypass surgery (67.9%); prior coronary percutaneous intervention
      (85.7%); prior myocardial infarction (82.1%); diabetes (67.9%); and mean ejection
      fraction of 33.1%. No statistical difference was seen between baseline RDS score
      and that after placebo or ranolazine (n=20) (P>=0.05). There was however, an
      improvement in anginal frequency (8/10 patients) (P=0.058), quality of life (8/10
      patients) (P=0.048), and mean score of all components of the SAQ questionnaire
      (n=10) (P=0.047) with ranolazine compared with placebo. CONCLUSION: In optimally
      treated ICM patients with continued chest pain or dyspnea, ranolazine possibly
      had a positive impact on quality of life, a reduction in anginal frequency, and
      an overall improvement in the mean SAQ component score compared with baseline.
      Ranolazine did not change the dyspnea score compared with baseline.

PMID- 25848290
TI  - Epidemiology of Japanese encephalitis: past, present, and future prospects.
AB  - Japanese encephalitis (JE) is one of severe viral encephalitis that affects
      individuals in Asia, western Pacific countries, and northern Australia. Although
      67,900 JE cases have been estimated among 24 JE epidemic countries annually, only
      10,426 have been reported in 2011. With the establishment of JE surveillance and
      vaccine use in some countries, the JE incidence rate has decreased; however,
      serious outbreaks still occur. Understanding JE epidemics and identifying the
      circulating JE virus genotypes will improve JE prevention and control. This
      review summarizes the current epidemiology data in these countries. 

PMID- 25848291
TI  - Pharmacokinetic drug interactions with clopidogrel: updated review and risk
      management in combination therapy.
AB  - BACKGROUND: Coprescribing of clopidogrel and other drugs is common. Available
      reviews have addressed the drug-drug interactions (DDIs) when clopidogrel is as
      an object drug, or focused on combination use of clopidogrel and a special class
      of drugs. Clinicians may still be ignorant of those DDIs when clopidogrel is a
      precipitant drug, the factors determining the degree of DDIs, and corresponding
      risk management. METHODS: A literature search was performed using PubMed,
      MEDLINE, Web of Science, and the Cochrane Library to analyze the pharmacokinetic
      DDIs of clopidogrel and new P2Y12 receptor inhibitors. RESULTS: Clopidogrel
      affects the pharmacokinetics of cerivastatin, repaglinide, ferulic acid,
      sibutramine, efavirenz, and omeprazole. Low efficacy of clopidogrel is
      anticipated in the presence of omeprazole, esomeprazole, morphine, grapefruit
      juice, scutellarin, fluoxetine, azole antifungals, calcium channel blockers,
      sulfonylureas, and ritonavir. Augmented antiplatelet effects are anticipated when
      clopidogrel is coprescribed with aspirin, curcumin, cyclosporin, St John's wort,
      rifampicin, and angiotensin-converting enzyme inhibitors. The factors determining
      the degree of DDIs with clopidogrel include genetic status (eg, cytochrome P540
      [CYP]2B6*6, CYP2C19 polymorphism, CYP3A5*3, CYP3A4*1G, and CYP1A2-163C.A),
      species differences, and dose strength. The DDI risk does not exhibit a class
      effect, eg, the effects of clopidogrel on cerivastatin versus other statins, the
      effects of proton pump inhibitors on clopidogrel (omeprazole, esomeprazole versus
      pantoprazole, rabeprazole), the effects of rifampicin on clopidogrel versus
      ticagrelor and prasugrel, and the effects of calcium channel blockers on
      clopidogrel (amlodipine versus P-glycoprotein-inhibiting calcium channel
      blockers). The mechanism of the DDIs with clopidogrel involves modulating CYP
      enzymes (eg, CYP2B6, CYP2C8, CYP2C19, and CYP3A4), paraoxonase-1, hepatic
      carboxylesterase 1, P-glycoprotein, and organic anion transporter family member
      1B1. CONCLUSION: Effective and safe clopidogrel combination therapy can be
      achieved by increasing the awareness of potential changes in efficacy and
      toxicity, rationally selecting alternatives, tailoring drug therapy based on
      genotype, checking the appropriateness of physician orders, and performing
      therapeutic monitoring.

PMID- 25848293
TI  - P-wave and QT dispersion in patients with conversion disorder.
AB  - OBJECTIVE: The aim of this study was to investigate QT dispersion (QTd), which is
      the noninvasive marker of ventricular arrhythmia and sudden cardiac death, and P
      wave dispersion, which is the noninvasive marker of atrial arrhythmia, in
      patients with conversion disorder (CD). PATIENTS AND METHODS: A total of 60
      patients with no known organic disease who were admitted to outpatient emergency
      clinic and were diagnosed with CD after psychiatric consultation were included in
      this study along with 60 healthy control subjects. Beck Anxiety Inventory and
      Beck Depression Scale were administered to patients and 12-lead electrocardiogram
      measurements were obtained. Pd and QTd were calculated by a single blinded
      cardiologist. RESULTS: There was no statistically significant difference in terms
      of age, sex, education level, socioeconomic status, weight, height, and body mass
      index between CD patients and controls. Beck Anxiety Inventory scores (25.2+/
      10.8 and 3.8+/-3.2, respectively, P<0.001) and Beck Depression Scale scores
      (11.24+/-6.15 and 6.58+/-5.69, respectively, P<0.01) were significantly higher in
      CD patients. P-wave dispersion measurements did not show any significant
      differences between conversion patients and control group (46+/-5.7 vs 44+/-5.5,
      respectively, P=0.156). Regarding QTc and QTd, there was a statistically
      significant increase in all intervals in conversion patients (416+/-10 vs 398+/
      12, P<0.001, and 47+/-4.8 vs 20+/-6.1, P<0.001, respectively). CONCLUSION: A
      similar relation to that in literature between QTd and anxiety and somatoform
      disorders was also observed in CD patients. QTc and QTd were significantly
      increased compared to the control group in patients with CD. These results
      suggest a possibility of increased risk of ventricular arrhythmia resulting from
      QTd in CD patients. Larger samples are needed to evaluate the clinical course and
      prognosis in terms of arrhythmia risk in CD patients.

PMID- 25848294
TI  - Umeclidinium bromide/vilanterol combination in the treatment of chronic
      obstructive pulmonary disease: a review.
AB  - Chronic obstructive pulmonary disease (COPD) is a common disease among the
      elderly that could be prevented by smoking cessation. As it is characterized by
      airflow limitation that is not fully reversible, bronchodilator therapy is the
      first choice of treatment. Symptomatic COPD patients with or without risk for
      future exacerbations have a strong indication for the permanent use of long- and
      ultralong-acting beta2-agonists and/or long-acting muscarinic antagonists.
      Combining bronchodilators is an effective approach, as they demonstrate synergic
      action at a cellular level and have additive clinical benefits and fewer adverse
      events compared with increased doses of the monocomponents. Novel fixed-dose
      combinations of long-acting beta2-agonists/long-acting muscarinic antagonists in
      one inhaler have been approved for clinical use by the US Food and Drug
      Administration and the European Medicines Agency. This review focuses on
      published clinical trials about the fixed-dose combination of
      umeclidinium/vilanterol trifenatate in patients with COPD. Results from six
      studies (five of them of 12 weeks' duration and one that lasted 1 year, including
      more than 6,000 patients in total) showed that umeclidinium/vilanterol
      trifenatate improved lung function, dyspnea, and health-related quality of life
      and decreased the exacerbation rate with no serious adverse events. More
      longstanding trials are needed to evaluate the effect of the drug on disease
      progression and compare it directly with other fixed-dose combinations. 

PMID- 25848295
TI  - Regular inhaled corticosteroids in adult-onset asthma and the risk for future
      cancer: a population-based cohort study with proper person-time analysis.
AB  - BACKGROUND: Recent studies have shown that inhaled corticosteroids (ICS) can
      exert anti-inflammatory effects for chronic airway diseases, and several
      observational studies suggest that they play a role as cancer chemopreventive
      agents, particularly against lung cancer. We aimed to examine whether regular ICS
      use was associated with a reduced risk for future malignancy in patients with
      newly diagnosed adult-onset asthma. METHODS: We used a population-based cohort
      study between 2001 and 2008 with appropriate person-time analysis. Participants
      were followed up until the first incident of cancer, death, or to the end of
      2008. The Cox model was used to derive an adjusted hazard ratio (aHR) for cancer
      development. Kaplan-Meier cancer-free survival curves of two groups were
      compared. RESULTS: The exposed group of 2,117 regular ICS users and the
      nonexposed group of 17,732 non-ICS users were assembled. After 7,365 (mean, 3.5
      years; standard deviation 2.1) and 73,789 (mean, 4.1 years; standard deviation
      2.4) person-years of follow-up for the ICS users and the comparator group of non
      ICS users, respectively, the aHR for overall cancer was nonsignificantly elevated
      at 1.33 with 95% confidence interval (CI), 1.00-1.76, P=0.0501. The Kaplan-Meier
      curves for overall cancer-free proportions of both groups were not significant
      (log-rank, P=0.065). Synergistic interaction of concurrent presence of regular
      ICS use was conducted using "ICS-negative and chronic obstructive pulmonary
      disease (COPD)-negative" as the reference. The aHR for the group of "ICS
      positive, COPD-negative" did not reach statistically significant levels with aHR
      at 1.38 (95% CI, 0.53-3.56). There was a statistically significant synergistic
      interaction of concurrent presence of regular ICS use and COPD with aHR at 3.78
      (95% CI, 2.10-6.81). CONCLUSION: The protective effect of regular ICS use in the
      studied East Asian patients with adult-onset asthma was not detectable, contrary
      to reports of previous studies that ICS might prevent the occurrence of future
      cancer.

PMID- 25848296
TI  - Distribution and resistance of pathogens in liver transplant recipients with
      Acinetobacter baumannii infection.
AB  - BACKGROUND: Drug-resistant Acinetobacter baumannii has become a major problem in
      liver transplant recipients. The aim of this study was to investigate the
      clinical presentation, distribution, and drug susceptibility characteristics in
      liver recipients with A. baumannii infection. METHODS: We retrospectively
      investigated 17 liver recipients who developed A. baumannii infection between
      January 1, 2007 and December 31, 2014. The distribution of A. baumannii and drug
      susceptibility characteristics were reviewed. RESULTS: Infectious complications
      due to A. baumannii appeared in 17 liver recipients, with a total of 24 episodes.
      Approximately 63% (15/24) of A. baumannii infections occurred within 2 weeks
      after transplantation. The most common source of infection was multiple culture
      positive sites (35.3%, n=6), followed by the intra-abdominal/biliary tract
      (23.5%, n=4) and lung (23.5%, n=4). Eight patients (47.1%) had a body temperature
      of 38 degrees C or higher at the onset of A. baumannii infection. Nine, seven,
      and 12 recipients had a serum creatinine level of >1.5 mg/dL, a white blood cell
      count of >15,000/mm(3), and a platelet count of <50,000/mm(3), respectively.
      There were five (29.4%) cases of septic shock and eight (47.1%) deaths. The rate
      of antibiotic resistance of A. baumannii to ten of 12 antibiotics investigated
      was more than 60%. Among the 24 infections caused by A. baumannii, 75% were
      carbapenem-resistant. The rods were relatively sensitive to tigecycline and
      cefoperazone-sulbactam. CONCLUSION: The clinical manifestations of A. baumannii
      infection included a high body temperature, a decreased platelet count, an
      elevated white blood cell count, and onset in the early period after
      transplantation as well as high mortality. The antibiotic resistance rate of A.
      baumannii was extremely high. Prevention measures and combination antibiotic
      therapy are needed to improve the outcomes of liver recipients with A. baumannii
      infections.

PMID- 25848297
TI  - Combination of tadalafil and finasteride for improving the symptoms of benign
      prostatic hyperplasia: critical appraisal and patient focus.
AB  - The evidence suggests that combination therapy for benign prostatic hyperplasia
      (BPH)-lower urinary tract symptoms (LUTS) using an alpha-blocker and a 5alpha
      reductase inhibitor has become well accepted. The combination of daily tadalafil
      and an alpha-blocker has also demonstrated benefit. This paper addresses
      combination therapy with daily tadalafil and finasteride for the treatment of BPH
      LUTS. Our results demonstrate that use of tadalafil and finasteride represents a
      logical extension of combination therapies. We analyze a landmark study by Casabe
      et al that demonstrates improved voiding symptoms as assessed by International
      Prostate Symptom Scores with a combination of tadalafil and finasteride compared
      with finasteride and placebo. Study patients had moderate to severe LUTS and
      prostate volumes >30 g. The additional benefit of improved erectile function as
      assessed by International Index of Erectile Function-erectile function domain
      scores with the addition of tadalafil was a secondary benefit. We propose that
      the ideal patient for combination therapy with tadalafil and finasteride has a
      prostate volume >30 g and desires additional benefit over monotherapy. For these
      men, improved erectile function without sexual side effects was a secondary
      benefit. 

PMID- 25848298
TI  - The unsolved case of "bone-impairing analgesics": the endocrine effects of
      opioids on bone metabolism.
AB  - The current literature describes the possible risks for bone fracture in chronic
      analgesics users. There are three main hypotheses that could explain the
      increased risk of fracture associated with central analgesics, such as opioids:
      1) the increased risk of falls caused by central nervous system effects,
      including sedation and dizziness; 2) reduced bone mass density caused by the
      direct opioid effect on osteoblasts; and 3) chronic opioid-induced hypogonadism.
      The impact of opioids varies by sex and among the type of opioid used (less, for
      example, for tapentadol and buprenorphine). Opioid-associated androgen deficiency
      is correlated with an increased risk of osteoporosis; thus, despite that
      standards have not been established for monitoring and treating opioid-induced
      hypogonadism or hypoadrenalism, all patients chronically taking opioids
      (particularly at doses >=100 mg morphine daily) should be monitored for the early
      detection of hormonal impairment and low bone mass density. 

PMID- 25848299
TI  - Alemtuzumab for the treatment of multiple sclerosis.

PMID- 25848300
TI  - Prostanoid therapies in the management of pulmonary arterial hypertension.
AB  - Prostacyclin is an endogenous eicosanoid produced by endothelial cells; through
      actions on vascular smooth-muscle cells, it promotes vasodilation. Pulmonary
      arterial hypertension (PAH) is characterized by elevated mean pulmonary artery
      pressure due to a high pulmonary vascular resistance state. A relative decrease
      in prostacyclin presence has been associated with PAH; this pathway has thus
      become a therapeutic target. Epoprostenol, the synthetic equivalent of
      prostacyclin, was first utilized as short-term or bridging therapy in the 1980s.
      Further refinement of its long-term use via continuous intravenous infusion
      followed. A randomized controlled trial by Barst et al in 1996 demonstrated
      functional, hemodynamic, and mortality benefits of epoprostenol use. This work
      was a groundbreaking achievement in the management of PAH and initiated a wave of
      research that markedly altered the dismal prognosis previously associated with
      PAH. Analogs of prostacyclin, including iloprost and treprostinil, exhibit
      increased stability and allow for an extended array of parenteral and non
      parenteral (inhaled and oral) therapeutic options. This review further examines
      the pharmacology and clinical use of epoprostenol and its analogs in PAH. 

PMID- 25848301
TI  - Lowering triglycerides to modify cardiovascular risk: will icosapent deliver?
AB  - Despite the clinical benefits of lowering levels of low-density lipoprotein
      cholesterol, many patients continue to experience cardiovascular events. This
      residual risk suggests that additional risk factors require aggressive
      modification to result in more effective prevention of cardiovascular disease.
      Hypertriglyceridemia has presented a considerable challenge with regard to
      understanding its role in the promotion of cardiovascular risk. Increasing
      evidence has established a clear causal role for elevated triglyceride levels in
      vascular risk. As a result, there is increasing interest in the development of
      specific therapeutic strategies that directly target hypertriglyceridemia. This
      has seen a resurgence in the use of omega-3 fatty acids for the therapeutic
      lowering of triglyceride levels. The role of these agents and other emerging
      strategies to reduce triglyceride levels in order to decrease vascular risk are
      reviewed. 

PMID- 25848302
TI  - Experimental study of sutureless vascular anastomosis with use of glued
      prosthesis in rabbits.
AB  - OBJECTIVE: The objective of this study is to explore the feasibility and efficacy
      of a new technique for sutureless vascular anastomosis, using glued prosthesis,
      as a sole anastomosis fixation method in rabbits. METHODS: Ten rabbits were
      randomly selected to conduct the experiment. Five rabbits underwent direct
      anastomosis of infrarenal abdominal aorta, with glued prosthesis. In five other
      rabbits, reconstruction was done by sutured anastomosis. All animals were
      immediately examined by echo-Doppler for patency of anastomosis. The burst
      pressure of the glued anastomosis was measured and compared with that of a
      sutured artery. The animals were euthanized, and tissue samples were taken for
      histological examination immediately after the experiment. RESULTS: Compared to
      conventional anastomoses, sutureless vascular anastomoses required shorter time
      of creation and significantly reduced blood loss (P<5%). There was no significant
      difference on the average blood flow through the anastomosis between two groups
      at the end of surgery. All anastomoses with glued prosthesis, examined by echo
      Doppler, were patent at the anastomotic site, except one, which was stenosed
      immediately after surgery. In the control group, except one with stenosis, all
      conventional anastomoses were patent. Mean burst pressure at the anastomotic site
      for sutureless anastomoses was lower than in control group. Macroscopically, the
      BioGlue did not demonstrate any adhesion to the surrounding tissue as it was
      covered by the vascular prosthesis. Histological examination showed low-grade
      inflammatory reaction in glued anastomoses versus no inflammatory reaction at the
      sutured anastomoses. CONCLUSION: This technique may provide a feasible and
      successful alternative in vascular surgery. However, further long-term studies
      are necessary to elucidate the break pressure and degree of inflammation at the
      anastomotic site.

PMID- 25848303
TI  - Improving patient experience in a pediatric ambulatory clinic: a mixed method
      appraisal of service delivery.
AB  - OBJECTIVE: In 2013, customer satisfaction surveys showed that patients were
      unhappy with the services provided at our ambulatory clinic. In response, we
      performed an appraisal of our services, which resulted in the development of a
      strategy to reduce waiting time and improve quality of service. Infrastructural
      changes to our clinic's waiting room, consultation rooms, and back offices were
      performed, and schedules were redesigned to reduce wait time to 10 minutes and
      increase consultation time to 20 minutes. Our objective was to identify if this
      would improve 1) accessibility to caregivers and 2) quality of service and
      available amenities. DESIGN: We conducted a multi-method survey using 1) a
      patient flow analysis to analyze the flow of service and understand the impact of
      our interventions on patient flow and 2) specially designed questionnaires to
      investigate patients' perceptions of our wait time and how to improve our
      services. RESULTS: The results showed that 79% of our respondents were called in
      to see a doctor within 20 minutes upon arrival. More patients (55%) felt that 10
      20 minutes was an acceptable wait time. We also observed a perceived increase in
      satisfaction with wait time (94%). Finally, a large number of patients (97%) were
      satisfied with the quality of service and with the accessibility to caregivers
      (94%). CONCLUSION: The majority of our patients were satisfied with the
      accessibility to our ambulatory clinics and with the quality of services
      provided. The appraisal of our operational processes using a patient flow
      analysis also demonstrated how this strategy could effectively be applied to
      investigate and improve quality of service in patients.

PMID- 25848304
TI  - Morbid obese adults increased their sense of coherence 1 year after a patient
      education course: a longitudinal study.
AB  - BACKGROUND: Personal factors are key elements to understand peoples' health
      behavior. Studies of such factors are important to develop targeted interventions
      to improve health. The main purpose of this study is to explore sense of
      coherence (SOC) in a sample of persons with morbid obesity before and after
      attending a patient education course and to explore the association between SOC
      and sociodemographic and other personal factors. METHODS: In this longitudinal
      purposely sampled study, the participants completed questionnaires on the first
      day of the course and 12 months after course completion. Sixty-eight participants
      had valid scores on the selected variables at follow-up: SOC, self-esteem, and
      self-efficacy. Relationships were assessed with correlation analyses and paired
      and independent samples t-tests and predictors with linear regression analyses.
      RESULTS: From baseline to follow-up, the total SOC score and the subdimension
      scores comprehensibility, manageability, and meaningfulness all increased
      significantly. At both time points, the SOC scores were low compared to the
      general population but similar to scores in other chronically ill. At baseline, a
      multivariate analysis showed that older age, having paid work, and higher self
      esteem were directly related to higher total SOC score after controlling for
      other sociodemographic factors and the participants' level of self-efficacy.
      Multivariate analyses of the relationship between baseline predictors of SOC at
      12-month follow-up, controlling for baseline SOC scores or sociodemographic or
      personal factors, revealed that none of these variables independently predicted
      SOC scores at follow-up. CONCLUSION: The total SOC score and its subdimensions
      increased significantly at follow-up. SOC may be a useful outcome measure for
      lifestyle interventions in people with morbid obesity and possibly other health
      care problems. Subdimension scores may give an indication of what is poorly
      developed and needs strengthening. This might guide choices for targeted
      cognitive and psychosocial interventions. Further studies are needed to explore
      this issue with larger samples.

PMID- 25848305
TI  - Clinical significance of ALDH2 rs671 polymorphism in esophageal cancer: evidence
      from 31 case-control studies.
AB  - BACKGROUND: Aldehyde dehydrogenase 2 (ALDH2), a critical enzyme for the
      detoxification of alcohol, is associated with many types of cancers. To verify
      the relationship of ALDH2 rs671 G>A polymorphism and esophageal cancer (EC), we
      performed a meta-analysis of a total of 31 published data including 8,510
      patients and 16,197 controls. METHODS: The pooled odds ratio (OR) and the 95%
      confidence interval (CI) were calculated using a fixed or random-effects model.
      Heterogeneity (PH ), publication bias, and sensitivity analysis were also
      determined. RESULTS: Although a protective effort was found in the rs671
      homozygote comparison (AA/GG: OR=0.69; 95% CI=0.48-0.98), the heterozygote
      comparison was apparently associated with the risk of EC, particularly in the
      Chinese population ( AG/GG: OR=1.39; 95% CI=1.03-1.87). Alcohol consumption
      remarkably increased this risk, especially in the AG genotype. Drinking men with
      the AG genotype appeared to show a higher risk ( AG/GG: OR=4.39; 95% CI=1.24
      6.55) than drinking women. CONCLUSION: The present meta-analysis provided
      advanced information regarding the association of the ALDH2 A>G polymorphism and
      EC. Taken together, insights from this study suggested an enhanced effect on the
      development of EC through a genetic-environmental interaction.

PMID- 25848306
TI  - Protective effect of gonadotropin-releasing hormone analog on the ovarian reserve
      in rats receiving cyclophosphamide treatment.
AB  - OBJECTIVE: The aim of the study reported here was to investigate the protective
      effect of gonadotropin-releasing hormone analog (GnRHa) against cyclophosphamide
      (CTX)-induced gonadotoxicity. METHODS: Eighty Fischer 344 rats were divided
      randomly into four groups (20 per group). One group received normal saline, one
      GnRHa, one CTX, and one GnRHa+CTX. Several parameters were used to observe the
      ovarian reserve, including ovary weight, follicle number and diameter,
      concentrations of estradiol (E2) and follicle-stimulating hormone (FSH), and
      expressions of sex hormone receptors. RESULTS: When treatment was finished, the
      number of small follicles in the GnRHa+CTX group was significantly higher than in
      the CTX-alone group. Thirty days after treatment, the ovary weight, percentage of
      small follicles, mean follicular diameter, and serum concentrations of E2 and FSH
      in the GnRHa+CTX group all recovered, approaching normal levels. Sex hormone
      receptors did not show significant differences between the four groups.
      CONCLUSION: Combination treatment with GnRHa could prevent CTX-induced damage to
      ovarian reserve.

PMID- 25848307
TI  - Postnatal oogenesis in humans: a review of recent findings.
AB  - In spite of generally accepted dogma that the total number of follicles and
      oocytes is established in human ovaries during the fetal period of life rather
      than forming de novo in adult ovaries, some new evidence in the field challenges
      this understanding. Several studies have shown that different populations of stem
      cells, such as germinal stem cells and small round stem cells with diameters of 2
      to 4 MUm, that resembled very small embryonic-like stem cells and expressed
      several genes related to primordial germ cells, pluripotency, and germinal
      lineage are present in adult human ovaries and originate in ovarian surface
      epithelium. These small stem cells were pushed into the germinal direction of
      development and formed primitive oocyte-like cells in vitro. Moreover, oocyte
      like cells were also formed in vitro from embryonic stem cells and induced
      pluripotent stem cells. This indicates that postnatal oogenesis is not excluded.
      It is further supported by the occurrence of mesenchymal stem cells that can
      restore the function of sterilized ovaries and lead to the formation of new
      follicles and oocytes in animal models. Both oogenesis in vitro and
      transplantation of stem cell-derived "oocytes" into the ovarian niche to direct
      their natural maturation represent a big challenge for reproductive biomedicine
      in the treatment of female infertility in the future and needs to be explored and
      interpreted with caution, but it is still very important for clinical practice in
      the field of reproductive medicine. 

PMID- 25848308
TI  - Evaluation of the appropriateness of imipenem/cilastatin prescription and dosing
      in a tertiary care hospital.
AB  - BACKGROUND: Imipenem/cilastatin is an antibacterial agent of the carbapenem class
      of beta-lactams that is known to have an extremely wide spectrum of activity
      against Gram-positive, Gram-negative, aerobic, anaerobic, and even multidrug
      resistant strains. The objective of this study was to evaluate the appropriate
      use of imipenem/cilastatin in a local tertiary care hospital. The study assessed
      the indication both empirically and after the culture results were available, the
      dose and dose adjustment in renal failure, as well as the incidence of seizure in
      hospitalized patients receiving imipenem/cilastatin. METHODS: This observational
      study was conducted in a tertiary care hospital over a 3-month period. The
      treatment of 100 patients with imipenem/cilastatin was evaluated both empirically
      and after culture results were available. Analysis of the appropriateness of
      imipenem/cilastatin indication, dose, and monitoring of seizure frequency was
      based on the package insert, updated published guidelines, and clinical judgment.
      RESULTS: Patients from internal medicine and intensive care units comprised
      approximately 50% of the population in the study. The patients received
      imipenem/cilastatin mainly for urinary tract infections (27%) or for sepsis of an
      unknown focus (22%). The use of imipenem/cilastatin empirically was appropriate
      in 97.2% (n=69/71) of the cases, and its use postculture in 86% of the cases.
      There were 29% of the patients who were not started on imipenem/cilastatin
      empirically. Four patients out of the 29 patients (13.8%) who were not started on
      imipenem/cilastatin empirically inappropriately received imipenem/cilastatin post
      culture results. Thirty-three patients (33%) were not dosed appropriately, 30 of
      whom had renal impairment and creatinine clearance fluctuations. Only one patient
      developed a seizure while on imipenem/cilastatin. CONCLUSION: The prescription of
      imipenem/cilastatin at our setting was mostly appropriate to what is recommended
      in the guidelines and the literature, although a few cases could have been
      managed better. Dosage adjustment, however, was not as appropriate, mainly in
      patients who did not have a stable creatinine clearance.

PMID- 25848309
TI  - Disability-adjusted life years lost due to diabetes in France, Italy, Germany,
      Spain, and the United Kingdom: a burden of illness study.
AB  - AIMS: To compare the burden of disease (BoD) attributable to diabetes expressed
      in disability-adjusted life years (DALYs) for five European countries in 2010.
      METHODS: DALYs lost to diabetes as the sum of years of life lost and years lived
      with disability were estimated by sex and age using country-specific
      epidemiological data and global disability weights. Data from various secondary
      sources were combined to estimate health loss due to diabetes for France,
      Germany, Italy, Spain, and the UK. National statistical databases were used and
      if necessary, community studies were used to derive the prevalence of diabetes by
      sex and age group, which were weighted proportionately for a national population
      burden of disease estimate. All identified data were adapted to the Global Burden
      of Disease methodology (2010) to calculate the burden attributable to diabetes.
      No age weighting and discounting was applied. Sensitivity to different sources of
      variation was examined. Germany and Italy lost the largest number of DALYs due to
      diabetes, with 5.9 and 5.8 per 1,000 inhabitants, respectively, followed by Spain
      (4.4), France (3.7), and the UK (2.9). The highest burden was caused by mortality
      due to diabetes, with the exception of the UK, for which the burden due to
      disability of diabetes was higher. Mean DALYs lost were higher for women in
      Germany, Italy, and Spain and shown to increase with age for all countries.
      Sensitivity analysis in variation in disability weights and uncertainty in
      epidemiological data were shown to have effects on DALYs lost. CONCLUSION: In
      spite of data limitations, the estimates reported here show that DALY loss due to
      diabetes imposes a substantial burden on countries. Cross-national variation in
      disease epidemiology was the largest source of variation in the burden of
      diabetes between countries.

PMID- 25848310
TI  - Effect of eprosartan-based antihypertensive therapy on coronary heart disease
      risk assessed by Framingham methodology in Canadian patients with diabetes:
      results of the POWER survey.
AB  - OBJECTIVE: As part of the Physicians' Observational Work on Patient Education
      According to their Vascular Risk (POWER) survey, we used Framingham methodology
      to examine the effect of an eprosartan-based regimen on total coronary heart
      disease (CHD) risk in diabetic patients recruited in Canada. METHODS: Patients
      with new or uncontrolled hypertension (sitting systolic blood pressure [SBP] >140
      mmHg with diastolic blood pressure <110 mmHg) were identified at 335 Canadian
      primary care practices. Initial treatment consisted of eprosartan 600 mg/day,
      which was later supplemented with other antihypertensives as required. Outcomes
      included change in SBP at 6 months (primary objective) and absolute change in the
      Framingham 10-year CHD risk score (secondary objective). RESULTS: We identified
      an intention-to-treat diabetes population of 195 patients. Most diabetic patients
      were prescribed two or more antihypertensive drugs throughout the survey. Mean
      reductions in SBP and diastolic blood pressure were 20.8+/-14.8 mmHg and 9.5+/
      10.7 mmHg, respectively. The overall absolute mean 10-year CHD risk, calculated
      using Framingham formulae, declined by 2.9+/-3.5 points (n=49). Average baseline
      risk was higher in men than women (14.8+/-8.6 versus 5.6+/-1.8 points); men also
      had a larger average risk reduction (4.2+/-4.3 versus 1.5+/-1.3 points). The
      extent of absolute risk reduction also increased with increasing age (trend not
      statistically significant). CONCLUSION: Eprosartan-based therapy substantially
      reduced arterial blood pressure in our subset of diabetic patients; while there
      was a slight reduction in Framingham risk, there are indications from our data
      that both blood pressure control and the wider management of CHD risk in diabetic
      patients remains suboptimal in Canadian primary care.

PMID- 25848311
TI  - Aggressive digital papillary adenocarcinoma - a rare malignant tumor of the sweat
      glands: two case reports and a review of the literature.
AB  - Aggressive digital papillary adenocarcinomas are rare malignant tumors often
      located on the digits of the hand. Due to lack of pain, slow growth, and an
      inconspicuous appearance, diagnosis is often missed or delayed. We report two
      cases and review the present literature to give recommendations for diagnosis and
      treatment. 

PMID- 25848312
TI  - Successful use of a topical mixture with ozolipoile in the treatment of actinic
      ulcers.
AB  - PURPOSE: Post-radiation skin damage is the result of alterations produced in the
      irradiated zone. There are different studies aimed at verifying the effectiveness
      of several kinds of molecules in the treatment of radiation-induced skin damage.
      The purpose of this study is to test a mixture with a formulation containing
      several natural active ingredients on actinic ulcers in patients receiving
      radiation therapies. PATIENTS AND METHODS: The authors recruited 13 patients, and
      randomly divided them into a test group (T1) and a control group (T2). The
      patients in both groups were undergoing radiotherapy. The T1 group was treated
      with a mixture called ozolipoile, whereas the T2 group was administered
      hyaluronic acid gel followed by non-ablative laser therapy. We evaluated the
      obtained results, the time of clinical healing, the reduction of pain, and each
      side effect, comparing all data between the T1 and T2 groups. RESULTS: The
      average Visual Analog Scale results showed decrease in pain in both groups;
      however, while the T1 group showed a significant decrease in the values, the T2
      group reported a more gradual reduction in the values, without ever reaching the
      minimum values obtained with the treatment with ozolipoile. CONCLUSION: Treatment
      of actinic ulcers with ozolipoile mixture leads to faster control of pain and to
      better healing of small-size ulcers.

PMID- 25848313
TI  - Inflammatory bowel disease and anxiety: links, risks, and challenges faced.
AB  - Inflammatory bowel disease (IBD) causes severe physical symptoms and is also
      associated with psychological comorbidities. Abnormal anxiety levels are found in
      up to 40% of patients with IBD. Anxiety symptoms are often related to flares of
      IBD but may persist in times of remission. Detection of anxiety disorder (AD) in
      patients with IBD can be challenging. Patients with anxiety may also exhibit
      symptoms in keeping with functional gastrointestinal disorders (FGID). Evidence
      for the effectiveness of pharmacological and psychological therapies for anxiety
      stems from patients without IBD. Studies in patients with IBD have either been
      small or shown negative results. In light of this, a combined approach involving
      IBD physicians to improve disease control and psychologists or psychiatrists to
      treat anxiety is advised. This review examines the evidence of anxiety issues in
      IBD with a focus on extent of the problem, risk factors for anxiety, and the
      effectiveness of interventions. 

PMID- 25848314
TI  - Respiratory metapneumoviral infection without co-infection in association with
      acute and chronic lung allograft dysfunction.
AB  - BACKGROUND: Metapneumoviral respiratory infection is a community-acquired
      respiratory viral (CARV) infection. Lung transplantation recipients exposed to
      CARV are at risk for development of allograft rejection. The cellular and
      molecular pathways initiated by viral infection leading to allograft dysfunction
      are not completely understood. The aim of this study was to identify human
      metapneumoviral (hMPV) cases in association with allograft rejection. METHODS: A
      literature search was conducted to identify cases of both hMPV and allograft
      rejection within 6 months of the initial infection. This resulted in 1,007 lung
      transplantation recipients, with a total of 2,883 samples identified. Of these,
      57 demonstrated isolated hMPV without co-infection with other agents. RESULTS:
      The results of the study indicate that 35% of acute hMPV infections without co
      infection, at the time of detection by molecular diagnostic platforms, were
      associated with acute cellular rejection within 3 months. There were 9.4% of the
      cases subsequently associated with chronic allograft dysfunction/bronchiolitis
      obliterans syndrome, which was collectively termed chronic rejection for purposes
      of analysis. In conclusion, the prompt identification of isolated hMPV from lung
      transplantation patients is an important treatable risk factor for subsequent
      allograft dysfunction. The cellular and molecular pathogenesis of viral-induced
      allograft rejection remains a topic of future study.

PMID- 25848315
TI  - The effects of grounding (earthing) on inflammation, the immune response, wound
      healing, and prevention and treatment of chronic inflammatory and autoimmune
      diseases.
AB  - Multi-disciplinary research has revealed that electrically conductive contact of
      the human body with the surface of the Earth (grounding or earthing) produces
      intriguing effects on physiology and health. Such effects relate to inflammation,
      immune responses, wound healing, and prevention and treatment of chronic
      inflammatory and autoimmune diseases. The purpose of this report is two-fold: to
      1) inform researchers about what appears to be a new perspective to the study of
      inflammation, and 2) alert researchers that the length of time and degree
      (resistance to ground) of grounding of experimental animals is an important but
      usually overlooked factor that can influence outcomes of studies of inflammation,
      wound healing, and tumorigenesis. Specifically, grounding an organism produces
      measurable differences in the concentrations of white blood cells, cytokines, and
      other molecules involved in the inflammatory response. We present several
      hypotheses to explain observed effects, based on current research results and our
      understanding of the electronic aspects of cell and tissue physiology, cell
      biology, biophysics, and biochemistry. An experimental injury to muscles, known
      as delayed onset muscle soreness, has been used to monitor the immune response
      under grounded versus ungrounded conditions. Grounding reduces pain and alters
      the numbers of circulating neutrophils and lymphocytes, and also affects various
      circulating chemical factors related to inflammation. 

PMID- 25848316
TI  - Repository corticotropin injection in a patient presenting with focal segmental
      glomerulosclerosis, rheumatoid arthritis, and optic neuritis: a case report.
AB  - BACKGROUND: Focal segmental glomerulosclerosis (FSGS) causes scarring or
      sclerosis of glomeruli that act as tiny filters in the kidneys, damage to which
      results in diminished ability to properly filter blood, resulting in the urinary
      loss of plasma proteins and subsequent proteinuria. CASE PRESENTATION: A 60-year
      old, white female with a history of intermittent proteinuria was referred by her
      primary care physician for renal dysfunction. Biopsy confirmed FSGS and she was
      treated with an angiotensin-converting enzyme inhibitor. She also had rheumatoid
      arthritis (RA) but no active synovitis and was maintained on prednisone 5 mg/d.
      She also complained of worsening vision in her right eye and was diagnosed with
      optic neuritis (ON). She remained stable for about 8 months when examination
      indicated FSGS relapse, and she reported painful RA flares. She was treated with
      Acthar((r)) Gel (40 mg biweekly) for 6 months, after which proteinuria and urine
      protein-to-creatinine ratio decreased to about half. Her ON improved, and she
      reported that she had fewer RA flares and pain improved by 50%. This case of
      confirmed FSGS showed an improved response to treatment with Acthar Gel for FSGS
      with concomitant RA and ON. CONCLUSION: This referral case is relevant to primary
      care practitioners who treat disorders that may be responsive to corticosteroid
      therapy. The antiproteinuric effects and ancillary improvement in RA and ON
      symptoms during treatment with Acthar Gel are not entirely explained by its
      steroidogenic actions. ACTH is a bioactive peptide that, together with alpha
      melanocyte-stimulating hormone, exhibits biologic efficacy by modulating
      proinflammatory cytokines and subsequent leukocyte extravasation and may have
      autocrine/paracrine effects in joints. While Acthar Gel was primarily
      administered in this case to treat proteinuria, it also showed ancillary benefits
      in patients with concomitant inflammatory disease states.

PMID- 25848317
TI  - Surviving severe traumatic brain injury in Denmark: incidence and predictors of
      highly specialized rehabilitation.
AB  - PURPOSE: To identify all hospitalized patients surviving severe traumatic brain
      injury (TBI) in Denmark and to compare these patients to TBI patients admitted to
      highly specialized rehabilitation (HS-rehabilitation). PATIENTS AND METHODS:
      Patients surviving severe TBI were identified from The Danish National Patient
      Registry and The Danish Head Trauma Database. Overall incidence rates of
      surviving severe TBI and incidence rates of admission to HS-rehabilitation after
      severe TBI were estimated and compared. Patient-related predictors of no
      admission to HS-rehabilitation among patients surviving severe TBI were
      identified using multivariable logistic regression. RESULTS: The average
      incidence rate of surviving severe TBI was 2.3 per 100,000 person years.
      Incidence rates of HS-rehabilitation were generally stable around 2.0 per 100,000
      person years. Overall, 84% of all patients surviving severe TBI were admitted to
      HS-rehabilitation. Female sex, older age, and non-working status pre-injury were
      independent predictors of no HS-rehabilitation among patients surviving severe
      TBI. CONCLUSION: The incidence rate of hospitalized patients surviving severe TBI
      was stable in Denmark and the majority of the patients were admitted to HS
      rehabilitation. However, potential inequity in access to HS-rehabilitation may
      still be present despite a health care system based on equal access for all
      citizens.

PMID- 25848318
TI  - Does the use of a novel self-adhesive flowable composite reduce nanoleakage?
AB  - OBJECTIVE: The aim of the study reported here was to evaluate the performance of
      a self-adhesive flowable composite and two self-etching adhesive systems, when
      subjected to cyclic loading, in preventing the nanoleakage of Class V
      restorations. METHODS: Wedge-shape Class V cavities were prepared (4*2*2 mm
      [length * width * depth]) on the buccal surfaces of 90 sound human premolars.
      Cavities were divided randomly into three groups (n=30) according to the used
      adhesive (Xeno((r)) V [self-etching adhesive system]) and BOND-1((r)) SF (solvent
      free self-etching adhesive system) in conjunction with Artiste((r)) Nano
      Composite resin, and FusioTM Liquid Dentin (self-adhesive flowable composite),
      consecutively. Each group was further divided into three subgroups (n=10): (A)
      control, (B) subjected to occlusal cyclic loading (90N for 5,000 cycles), and (C)
      subjected to occlusal cyclic loading (90N for 10,000 cycles). Teeth then were
      coated with nail polish up to 1 mm from the interface, immersed in 50% silver
      nitrate solution for 24 hours and tested for nanoleakage using the environmental
      scanning electron microscopy and energy dispersive analysis X-ray analysis. Data
      were statistically analyzed using two-way analysis of variance and Tukey's post
      hoc tests (P<=0.05). RESULTS: The Fusio Liquid Dentin group showed statistically
      significant lower percentages of silver penetration (0.55 MU) compared with the
      BOND-1 SF (3.45 MU) and Xeno V (3.82 MU) groups, which were not statistically
      different from each other, as they both showed higher silver penetration.
      CONCLUSION: Under the test conditions, the self-adhesive flowable composite
      provided better sealing ability. Aging of the two tested adhesive systems, as a
      function of cyclic loading, increased nanoleakage.

PMID- 25848319
TI  - Health care coverage among long-distance truckers in India: an evaluation based
      on the Tanahashi model.
AB  - Long-distance truckers (LDTDs) are vulnerable to human immunodeficiency virus
      infection and other sexually transmitted infections due to the nature of their
      work, working environment, and frequent mobility. This paper examines and
      comments on the health care coverage provisioned under "Kavach" Project. Data
      from the Integrated Behavioural and Biological Survey, National Highway gathered
      from 2,066 LDTDs in Round 1 and 2,085 LDTDs in Round 2, who traveled in four
      extreme road corridors travelled by LDTDs in India, were used for analysis.
      Analysis reveals that service capacity in terms of socially marketed condoms per
      thousand LDTDs has increased from Round 1 to Round 2 (4,430 to 6,876,
      respectively). Accessibility coverage in terms of knowledge about the Khushi
      clinic has significantly decreased between Rounds 1 and 2 (60.9% to 54.6%;
      P<0.001). Acceptability coverage has increased between the two rounds (13.8% to
      50.6%; P<0.001). Contact coverage has also increased between the rounds (12.7% to
      22.3%; P<0.001). Effectiveness coverage for preventive and curative care has also
      increased significantly. This paper comments on the gaps in accessibility and
      acceptability of health care coverage and emphasizes the need for further studies
      to assess the contextual factors that influence the effectiveness and efficiency
      of interventions designed to address access barriers and to identify what
      combination of interventions may generate the best possible outcome. 

PMID- 25848320
TI  - Comparative analysis of prevalence of intimate partner violence against women in
      military and civilian communities in Abuja, Nigeria.
AB  - INTRODUCTION: Intimate partner violence (IPV) occurs across the world, in various
      cultures, and affects people across societies irrespective of economic status or
      gender. Most data on IPV before World Health Organization multicountry study
      (WHOMCS) usually came from sources other than the military. Result of this study
      will contribute to the existing body of knowledge and may serve as a baseline for
      future studies in military populations. This study compares the prevalence of the
      different types of IPV against women in military and civilian communities in
      Abuja, Nigeria. METHODS: Using a multistage sampling technique, 260 women who had
      intimate male partners were selected from military and civilian communities of
      Abuja. Collected data on personal characteristics and different types of IPV
      experienced were analyzed to demonstrate comparison of the association between
      the different forms of IPV and the respondents' sociodemographic and partner
      characteristics in the two study populations using percentages and chi-square
      statistics, and P-value was assumed to be significant at <=0.05. RESULTS: The
      prevalence of the four major types of IPV was higher among the military
      respondents than among civilians: controlling behavior, 37.1% versus 29.1%;
      emotional/psychological abuse, 42.4% versus 13.4%; physical abuse, 19.7% versus
      5.9%, and sexual abuse, 9.2% versus 8.8%. Significantly more respondents from the
      military population (59 [45.4%]) compared to civilians (21 [19.4%]) were
      prevented by their partners from seeing their friends (P=0.000). The situation is
      reversed with regard to permission to seek health care for self, with civilians
      reporting a significantly higher prevalence (35 [32.4%]) than did military
      respondents (20 [15.4%]) (P=0.002). The military respondents were clearly at a
      higher risk of experiencing all the variants of emotional violence than the
      civilians (P=0.00). The commonest form of physical violence against women was
      "being slapped or having something thrown at them, that could hurt", which was
      markedly higher in the military (43 [33.1%]) than in the civilian population (10
      [9.3%]), (P<0.05). CONCLUSION: IPV is a significant public health problem in
      Abuja, and the military population is clearly at a higher risk of experiencing
      all forms of IPV compared to the civilian population. The military should
      encourage and finance research on effect of military operations and posttraumatic
      stress disorders on family relationships with a view of developing evidence-based
      treatment models for military personnel.

PMID- 25848322
TI  - Contraceptive practices and pregnancy intendedness among pregnant adolescents.
AB  - BACKGROUND: Adolescent pregnancy is a major health problem in many developing
      countries. OBJECTIVE: To assess contraceptive practices and pregnancy
      intendedness in pregnant adolescents. MATERIALS AND METHODS: This study was
      prospectively conducted from September 2013 to June 2014. All consecutively
      pregnant women between 15 and 19 years old attending the Antenatal Clinic at
      Srinagarind Hospital and the Khon Kaen Branch of the Planned Parenthood
      Association of Thailand were invited for participation. Face-to-face interviews
      by trained interviewers using standardized questionnaires were carried out.
      Logistic regression was used to determine an adjusted odds ratio (aOR) and 95%
      confidence interval (CI) of independent predictors. RESULTS: Two hundred
      participants were enrolled. Mean age was 17.2 years. One hundred and eighteen
      (59.0%) were currently in school. Seventy-five (37.5%) participants had never
      used any contraceptive methods. Of the 125 participants who had ever used
      contraception, regular use of contraceptives was reported in only 21 participants
      (16.8%). Only two participants (1.0%) had ever used an intrauterine device or
      implant. Participants' age was a significant independent factor associated with
      non-use of contraceptives (aOR, 6.42; 95% CI, 2.94-14.04). Of the 200
      participants, 132 (66.0%) declared that the pregnancy was unintended. Significant
      independent factors predicting unintended pregnancy were educational status (aOR,
      6.17; 95% CI, 3.27-13.75) and participants' age (aOR, 5.76; 95% CI, 2.42-13.70).
      CONCLUSION: Non-use and use of contraceptive methods with high failure rates were
      major reasons leading to adolescent pregnancies. Participants' age was an
      independent factor predicting non-use of contraceptives. Educational status and
      age of the participants were significant factors predicting unintended pregnancy.

PMID- 25848321
TI  - Vulvar cancer: epidemiology, clinical presentation, and management options.
AB  - EPIDEMIOLOGY: Vulvar cancer can be classified into two groups according to
      predisposing factors: the first type correlates with a HPV infection and occurs
      mostly in younger patients. The second group is not HPV associated and occurs
      often in elderly women without neoplastic epithelial disorders. HISTOLOGY:
      Squamous cell carcinoma (SCC) is the most common malignant tumor of the vulva
      (95%). CLINICAL FEATURES: Pruritus is the most common and long-lasting reported
      symptom of vulvar cancer, followed by vulvar bleeding, discharge, dysuria, and
      pain. THERAPY: The gold standard for even a small invasive carcinoma of the vulva
      was historically radical vulvectomy with removal of the tumor with a wide margin
      followed by an en bloc resection of the inguinal and often the pelvic lymph
      nodes. Currently, a more individualized and less radical treatment is suggested:
      a radical wide local excision is possible in the case of localized lesions (T1).
      A sentinel lymph node (SLN) biopsy may be performed to reduce wound complications
      and lymphedema. PROGNOSIS: The survival of patients with vulvar cancer is good
      when convenient therapy is arranged quickly after initial diagnosis. Inguinal
      and/or femoral node involvement is the most significant prognostic factor for
      survival.

PMID- 25848323
TI  - Clinical utility of ulipristal acetate for the treatment of uterine fibroids:
      current evidence.
AB  - Uterine myoma is the most common benign uterine tumor in women of reproductive
      age and occurs in 20%-25% of the worldwide population. No currently approved
      medical treatment is able to completely eliminate fibroids. Surgery, particularly
      hysterectomy, predominates as the treatment strategy of choice, even though it is
      associated with risks and complications and causes infertility. Until recently,
      gonadotropin-releasing hormone agonists were the only available drugs for the
      preoperative treatment of fibroids. However, ulipristal acetate (UPA), an oral
      selective progesterone receptor modulator, was recently licensed in Europe for
      the same indication. Recent studies have demonstrated the efficacy and safety of
      UPA in the medical management of fibroids before surgery, with a better
      tolerability profile than leuprolide acetate. Analyzing the literature, we
      identified new management strategies involving UPA and surgery, considering
      advantages of both medical and surgical therapy. The advent of UPA will
      undoubtedly modify the surgical approach to fibroids, but the heterogeneity of
      these possible indications now requires various original clinical studies to
      identify the optimal indications for UPA in patients with symptomatic fibroid(s).

PMID- 25848325
TI  - Pacing strategy in male elite and age group 100 km ultra-marathoners.
AB  - Pacing strategy has been investigated in elite 100 km and elite 161 km (100 mile)
      ultra-marathoners, but not in age group ultra-marathoners. This study
      investigated changes in running speed over segments in male elite and age group
      100 km ultra-marathoners with the assumption that running speed would decrease
      over segments with increasing age of the athlete. Running speed during segments
      in male elite and age group finishers for 5-year age groups (ie, 18-24 to 65-69
      years) in the 100 km Lauf Biel in Switzerland was investigated during the 2000
      2009 period. Average running speed over segment time station (TS) TS1-TS2 (56.1
      km) was compared with running speed Start-TS1 (38 km) and Start-TS3 (76.7 km) and
      running speed TS2-TS3 was compared with running speed Start-Finish. For the top
      ten athletes in each edition, running speed decreased from 2000 to 2009 for TS1
      TS2 and TS2-TS3 (P<0.0001) but not in TS3-Finish (P>0.05). During TS1-TS2,
      athletes were running at 98.0%+/-2.1% of the running speed of Start-TS1. In TS2
      TS3, they were running at 94.6%+/-3.4% of the running speed of TS1-TS2. In TS3
      Finish, they were running at 95.5%+/-3.8% of running speed in TS2-TS3. For age
      group athletes, running speed decreased in TS1-TS2 and TS2-TS3. In TS3-Finish,
      running speed remained unchanged with the exception of the age group 40-44 years
      for which running speed increased. Running speed showed the largest decrease in
      the age group 18-24 years. To summarize, the top ten athletes in each edition
      maintained their running speed in the last segment (TS3-Finish) although running
      speed decreased over the first two segments (TS1-TS2 and TS2-TS3). The best
      pacers were athletes in the age group 40-44 years, who were able to achieve
      negative pacing in the last segment (TS3-Finish) of the race. The negative pacing
      in the last segment (TS3-Finish) was likely due to environmental conditions, such
      as early dawn and the flat circuit in segment TS3-Finish of the race. 

PMID- 25848324
TI  - To mesh or not to mesh: a review of pelvic organ reconstructive surgery.
AB  - Pelvic organ prolapse (POP) is a major health issue with a lifetime risk of
      undergoing at least one surgical intervention estimated at close to 10%. In the
      1990s, the risk of reoperation after primary standard vaginal procedure was
      estimated to be as high as 30% to 50%. In order to reduce the risk of relapse,
      gynecological surgeons started to use mesh implants in pelvic organ
      reconstructive surgery with the emergence of new complications. Recent studies
      have nevertheless shown that the risk of POP recurrence requiring reoperation is
      lower than previously estimated, being closer to 10% rather than 30%. The
      development of mesh surgery - actively promoted by the marketing industry - was
      tremendous during the past decade, and preceded any studies supporting its
      benefit for our patients. Randomized trials comparing the use of mesh to native
      tissue repair in POP surgery have now shown better anatomical but similar
      functional outcomes, and meshes are associated with more complications, in
      particular for transvaginal mesh implants. POP is not a life-threatening
      condition, but a functional problem that impairs quality of life for women. The
      old adage "primum non nocere" is particularly appropriate when dealing with this
      condition which requires no treatment when asymptomatic. It is currently admitted
      that a certain degree of POP is physiological with aging when situated above the
      landmark of the hymen. Treatment should be individualized and the use of mesh
      needs to be selective and appropriate. Mesh implants are probably an important
      tool in pelvic reconstructive surgery, but the ideal implant has yet to be found.
      The indications for its use still require caution and discernment. This review
      explores the reasons behind the introduction of mesh augmentation in POP surgery,
      and aims to clarify the risks, benefits, and the recognized indications for its
      use. 

PMID- 25848326
TI  - Family medicine residents' perceived level of comfort in treating common sports
      injuries across residency programs in the United States.
AB  - BACKGROUND AND OBJECTIVE: Family physicians are expected to be comfortable in
      treating common sports injuries. Evidence shows a limited level of comfort in
      treating these injuries in pediatric and internal medicine residents. Studies are
      lacking, however, in family medicine residents. The purpose of this study is to
      assess the comfort level of family medicine residents in treating common sports
      injuries in adults and children based on their perceived level of knowledge and
      attitudes. METHODS: This is a cross-sectional study of family medicine residents
      in the United Sates. A written survey of 25 questions related to sports injury
      knowledge and factors affecting comfort level were collected. A chi-square test
      was implemented in calculating P-values. RESULTS: Five hundred and fifty-seven
      residents responded to the survey. A higher percentage of doctors of osteopathy
      (86.6%, 82.5%, 69.6%, and 68.7%) compared to doctors of medicine (78.5%, 71.6%,
      53.4%, and 52.8%) respectively identified ankle sprain, concussion, plantar
      fasciitis, and lateral epicondylitis as common injuries, and felt comfortable in
      treating them (P-values =0.015, 0.004, 0.0001, and 0.0002, respectively).
      Residents with high interest in sports medicine correctly identified the injuries
      as common and felt comfortable treating them as well (knowledge, P=0.027, 0.0029,
      <0.0001, and 0.0001, respectively; comfort level, P=0.0016, <0.0001, 0.0897, and
      0.0010, respectively). CONCLUSION: Medical education background, factors that
      affect training, and an interest in sports medicine contribute to residents'
      knowledge and comfort level in treatment of common sports injuries.

PMID- 25848327
TI  - Diagnosis, treatment, and rehabilitation of stress fractures in the lower
      extremity in runners.
AB  - Stress fractures account for between 1% and 20% of athletic injuries, with 80% of
      stress fractures in the lower extremity. Stress fractures of the lower extremity
      are common injuries among individuals who participate in endurance, high load
      bearing activities such as running, military and aerobic exercise and therefore
      require practitioner expertise in diagnosis and management. Accurate diagnosis
      for stress fractures is dependent on the anatomical area. Anatomical regions such
      as the pelvis, sacrum, and metatarsals offer challenges due to difficulty
      differentiating pathologies with common symptoms. Special tests and treatment
      regimes, however, are similar among most stress fractures with resolution between
      4 weeks to a year. The most difficult aspect of stress fracture treatment entails
      mitigating internal and external risk factors. Practitioners should address
      ongoing risk factors to minimize recurrence. 

PMID- 25848328
TI  - Finalizing a measurement framework for the burden of treatment in complex
      patients with chronic conditions.
AB  - PURPOSE: The workload of health care and its impact on patient functioning and
      well-being is known as treatment burden. The purpose of this study was to
      finalize a conceptual framework of treatment burden that will be used to inform a
      new patient-reported measure of this construct. PATIENTS AND METHODS: Semi
      structured interviews were conducted with 50 chronically ill patients from a
      large academic medical center (n=32) and an urban safety-net hospital (n=18). We
      coded themes identifying treatment burden, with the themes harmonized through
      discussion between multiple coders. Four focus groups, each with five to eight
      participants with chronic illness, were subsequently held to confirm the thematic
      structure that emerged from the interviews. RESULTS: Most interviewed patients
      (98%) were coping with multiple chronic conditions. A preliminary conceptual
      framework using data from the first 32 interviews was evaluated and was modified
      using narrative data from 18 additional interviews with a racially and
      socioeconomically diverse sample of patients. The final framework features three
      overarching themes with associated subthemes. These themes included: 1) work
      patients must do to care for their health (eg, taking medications, keeping
      medical appointments, monitoring health); 2) challenges/stressors that exacerbate
      perceived burden (eg, financial, interpersonal, provider obstacles); and 3)
      impacts of burden (eg, role limitations, mental exhaustion). All themes and
      subthemes were subsequently confirmed in focus groups. CONCLUSION: The final
      conceptual framework can be used as a foundation for building a patient self
      report measure to systematically study treatment burden for research and
      analytical purposes, as well as to promote meaningful clinic-based dialogue
      between patients and providers about the challenges inherent in maintaining
      complex self-management of health.

PMID- 25848329
TI  - The benefit of consolidation radiotherapy to initial disease bulk in patients
      with advanced Hodgkin's disease who achieved complete remission after standard
      chemotherapy.
AB  - BACKGROUND/PURPOSE: The aim of this study was to evaluate the role of
      consolidation radiotherapy (RT) in advanced-stage Hodgkin's disease (HD) with
      initial bulky sites after radiological complete remission (CR) or partial
      response (PR) with positron emission tomography-negative (metabolic CR) following
      standard chemotherapy (ABVD [Adriamycin, bleomycin, vinblastine, and
      dacarbazine]) six to eight cycles. PATIENTS AND METHODS: Adult patients with
      advanced-stage HD treated at our institute during the period 2006 to 2012 were
      retrospectively evaluated. One hundred and ninety-two patients with initial bulky
      disease size (>7 cm) who attained radiological CR/PR and metabolic CR were
      included in the analysis. One hundred and thirteen patients who received
      radiotherapy (RT) as consolidation postchemotherapy (RT group) were compared to
      79 patients who did not receive RT (non-RT group). Disease-free (DFS) and overall
      survival (OS) rates were estimated using the Kaplan-Meier method and were
      compared according to treatment group by the log-rank tests at P <=0.05
      significance level. RESULTS: The mean age of the cohort was 33 (range: 14 to 81)
      years. Eighty-four patients received involved-field radiation and 29 patients
      received involved-site RT. The RT group had worse prognostic factors compared to
      the non-RT group. Thirteen (12%) relapses occurred in the RT group, and 19 (24%)
      relapses occurred in the non-RT group. Nine patients (8%) in the RT group died,
      compared to eleven patients (14%) in the non-RT group. Second malignancies were
      seen in only five patients: three patients in the RT group compared to two
      patients in the non-RT group. At 5 years, overall DFS was 79%+/-9% and OS was
      85%+/-9%. There was significant statistical difference between the RT group and
      the non-RT group regarding 5-year DFS: 86%+/-7% and 74%+/-9%, respectively (P
      <=0.02). However, the 5-year OS was 90%+/-5% for the RT group and 83%+/-8% for
      the non-RT group, with no statistical difference (P <=0.3). CONCLUSION: The
      results of our study suggest that consolidation RT in patients with advanced
      stage HD with initial bulky disease who had postchemotherapy radiologic CR or PR
      with metabolic CR improved the DFS.

PMID- 25848330
TI  - A case of Hodgkin's lymphoma with severely impaired liver function treated
      successfully with gemcitabine followed by ABVD.
AB  - Hodgkin's lymphoma (HL) originates from clonal B cells and is the most common
      malignancy in the second decade of life. Liver involvement is uncommon at
      presentation in patients with HL and there is a paucity of data for treatment of
      patients with severely impaired liver function. We present an unusual case of HL
      with severe hepatic impairment, splenomegaly and multiple chromosomal
      abnormalities that was treated initially with gemcitabine and steroids. Once
      liver function tests improved, six cycles of Adriamycin, bleomycin, vinblastine,
      and dacarbazine were administered. The patient remains in remission at 3.5 years
      of follow-up. 

PMID- 25848331
TI  - Students' perceptions of the academic learning environment in seven medical
      sciences courses based on DREEM.
AB  - OBJECTIVE: Learning environment has a significant role in determining students'
      academic achievement and learning. The aim of this study is to investigate the
      viewpoints of undergraduate medical sciences students on the learning environment
      using the Dundee Ready Education Environment Measure (DREEM) at Rafsanjan
      University of Medical Sciences (RUMS). METHODS: The descriptive cross-sectional
      study was performed on 493 medical sciences students in the following majors:
      nursing, midwifery, radiology, operating room nursing, laboratory sciences,
      medical emergency, and anesthesia. The DREEM questionnaire was used as a standard
      tool. Data were analyzed using SPSS (v17) software. Student's t-tests and
      analysis of variance (ANOVA) statistical tests were used. RESULTS: The mean of
      the achieved scores in the five domains was 113.5 out of 200 (56.74%), which was
      considered to be more positive than negative. The total mean scores for
      perception of learning, teaching, and atmosphere were 27.4/48 (57.24%), 24.60/44
      (55.91%), and 26.8/48 (55.89%), respectively. Academic and social self
      perceptions were 20.5/32 (64.11%) and 15.7/28 (56.36%), respectively. The total
      DREEM scores varied significantly between courses (P<0.01). The total scores of
      the students of operating room nursing, anesthesia, and laboratory sciences,
      first year students, and females were significantly higher than the other
      students (P<0.01). CONCLUSION: The results have suggested that the students of
      medical sciences courses at RUMS generally hold positive perceptions toward their
      course environment. The differences between courses and their study pathway
      should be further investigated by analysis of specific items. Our results showed
      that it is essential for faculty members and course managers to make more efforts
      toward observing principles of instructional designs, to create an appropriate
      educational environment, and to reduce deficits in order to provide a better
      learning environment with more facilities and supportive systems for the
      students.

PMID- 25848332
TI  - A learning skills course for the 1st year medical students: an experience at a
      Saudi medical school.
AB  - BACKGROUND: Every year nearly 1,500 students enter into medical program after
      passing high school and national aptitude exams. However, many students
      experience frustration, failure, and psychological morbidities like stress,
      depression, and anxiety because they are not aware of their learning styles or do
      not have effective learning skills and strategies. The College of Medicine of Al
      Imam Muhammad ibn Saud Islamic University has adopted the outcome based,
      community oriented, Spiral Curriculum. Although the curriculum is innovative, on
      the other hand, it is very demanding. OBJECTIVE: The purpose of this paper is to
      share educational structure and evaluation results of the course on effective
      learning and study skills for the 1st year medical students. METHODS: To prepare
      our students in order to cope with this demanding but promising curriculum, we
      conducted an effective and comprehensive learning skills course for 16 weeks in
      the first semester of year 1 in the medical program. Performance of each student
      was assessed and the course evaluation was done by students at the end of the
      course. RESULTS: The attendance of the students throughout the course was over
      90%. The average performance of students in the summative assessment was 78% and
      the course was generally liked by the students. DISCUSSION: Students overall had
      a positive attitude toward the learning skills course. Majority of the students
      showed interest in attending the sessions regularly and realized the significance
      of this course to improve their learning skills.

PMID- 25848333
TI  - Perceptions of students in different phases of medical education of the
      educational environment: Universiti Sultan Zainal Abidin.
AB  - BACKGROUND: The Dundee Ready Education Environment Measure (DREEM) was planned
      and designed to quantify the educational environment precisely for medical
      schools and health-related professional schools. DREEM is now considered a valid
      and reliable tool, which is globally accepted for measuring the medical
      educational environment. The educational environment encountered by students has
      an impact on satisfaction with the course of study, perceived sense of well
      being, aspirations, and academic achievement. In addition to being measurable,
      the educational environment can also be changed, thus enhancing the quality of
      medical education and the environment, and the medical education process. The
      objective of this study was to assess the educational environment of the
      Universiti Sultan Zainal Abidin (UniSZA) undergraduate medical program from the
      students' perspective. The study expected to explore UniSZA medical students'
      overall perceptions, perceptions of learning, teachers, atmosphere, academic self
      perception, and social self-perception using the DREEM questionnaire. METHODS: A
      cross-sectional survey was conducted to study the perceptions of the students
      toward the educational environment of UniSZA as a new medical school, using the
      DREEM questionnaire. All medical students of UniSZA from Years I-V enrolled in
      the Bachelor of Medicine and Bachelor of Surgery programs were the target
      population (n=270). Therefore, the universal sampling technique was used. The
      data were analyzed using the SPSS 20 software. This study obtained ethical
      clearance from the Faculty of Medicine and Health Sciences, UniSZA. RESULTS: A
      total of 195 out of 270 students responded. Respondents included 31% males and
      69% females. The overall DREEM scores were significantly higher (P<0.001) for
      females than males. CONCLUSION: The medical students at UniSZA showed a positive
      perception of their educational environment. The new medical faculty, established
      for only a few years, has achieved an above-average, conducive educational
      environment for students. Most of the students showed a positive perception for
      the entire five domains tested in the DREEM survey. Females were consistently
      satisfied with UniSZA's educational environment, and self-perception was high, as
      compared to male undergraduates.

PMID- 25848334
TI  - Preliminary investigation into application of problem-based learning in the
      practical teaching of diagnostics.
AB  - BACKGROUND: Problem-based learning (PBL) is a pedagogical approach based on
      problems. Specifically, it is a student-centered, problem-oriented teaching
      method that is conducted through group discussions. The aim of our study is to
      explore the effects of PBL in diagnostic teaching for Chinese medical students.
      METHODS: A prospective, randomized controlled trial was conducted. Eighty junior
      clinical medical students were randomly divided into two groups. Forty students
      were allocated to a PBL group and another 40 students were allocated to a control
      group using the traditional teaching method. Their scores in the practice skills
      examination, ability to write and analyze medical records, and results on the
      stage test and behavior observation scale were compared. A questionnaire was
      administered in the PBL group after class. RESULTS: There were no significant
      differences in scores for writing medical records, content of interviewing,
      physical examination skills, and stage test between the two groups. However,
      compared with the control group, the PBL group had significantly higher scores on
      case analysis, interviewing skills, and behavioral observation scales.
      CONCLUSION: The questionnaire survey revealed that PBL could improve interest in
      learning, cultivate an ability to study independently, improve communication and
      analytical skills, and good team cooperation spirit. However, there were some
      shortcomings in systematization of imparting knowledge. PBL has an obvious
      advantage in teaching with regard to diagnostic practice.

PMID- 25848335
TI  - Systemic targeted therapy for her2-positive early female breast cancer: a
      systematic review of the evidence for the 2014 Cancer Care Ontario systemic
      therapy guideline.
AB  - BACKGROUND: This systematic review addresses the question "What is the optimal
      targeted therapy for female patients with early-stage human epidermal growth
      factor receptor 2 (her2)-positive breast cancer?" METHODS: The medline and embase
      databases were searched for the period January 2008 to May 2014. The Standards
      and Guidelines Evidence directory of cancer guidelines and the Web sites of major
      guideline organizations were also searched. RESULTS: Sixty publications relevant
      to the targeted therapy portion of the systematic review were identified. In four
      major trials (hera, National Surgical Adjuvant Breast and Bowel Project B-31,
      North Central Cancer Treatment Group N9831, and Breast Cancer International
      Research Group 006), adjuvant trastuzumab for 1 year was superior in disease-free
      survival (dfs) and overall survival (os) to no trastuzumab; trastuzumab showed no
      benefit in one trial (pacs 04). A shorter duration of trastuzumab (less than 1
      year compared with 1 year) was evaluated, with mixed results for dfs: one trial
      showed superiority (finher), one trial could not demonstrate noninferiority
      (phare), another trial showed equivalent results (E 2198), and one trial is still
      ongoing (persephone). Longer trastuzumab duration (hera: 2 years vs. 1 year)
      showed no improvement in dfs or os and a higher rate of cardiac events. Newer
      her2-targeted agents (lapatinib, pertuzumab, T-DM1, neratinib) have been or are
      still being evaluated in both adjuvant and neoadjuvant trials, either by direct
      comparison with trastuzumab alone or combined with trastuzumab. In the
      neoadjuvant setting (neoaltto, GeparQuinto, Neosphere), trastuzumab alone or in
      combination with another anti-her2 agent (lapatinib, pertuzumab) was compared
      with either lapatinib or pertuzumab alone and showed superior or equivalent rates
      of pathologic complete response. In the adjuvant setting, lapatinib alone or in
      combination with trastuzumab, compared with trastuzumab alone (altto) or with
      placebo (teach), was not superior in dfs. The results of the completed aphinity
      trial, evaluating the role of dual her2 blockade with trastuzumab and pertuzumab,
      are highly anticipated. Ongoing trials are evaluating trastuzumab as a single
      agent without adjuvant chemotherapy (respect) and in patients with low her2
      expression (National Surgical Adjuvant Breast and Bowel Project B-47).
      CONCLUSIONS: Taking into consideration disease characteristics and patient
      preference, 1 year of trastuzumab should be offered to all patients with her2
      positive breast cancer who are receiving adjuvant chemotherapy. Cardiac function
      should be regularly assessed in this patient population.

PMID- 25848336
TI  - Targeted therapy in her2-positive metastatic breast cancer: a review of the
      literature.
AB  - Breast tumours positive for her2 (human epidermal growth factor receptor 2)
      represent approximately 20% of all breast cancer cases and are associated with an
      aggressive natural history. The advent of targeted anti-her2 therapies has
      dramatically improved disease control and survival in patients with metastatic
      her2-positive breast cancer. Targeted agents are now considered the standard of
      care in the first-line setting and beyond. The present review summarizes the
      currently available data on targeted anti-her2 therapies from completed
      randomized phase iii clinical trials and briefly discusses emerging advances that
      will address unmet needs in metastatic her2-positive breast cancer. 

PMID- 25848337
TI  - Systemic treatment approaches in her2-negative advanced breast cancer-guidance on
      the guidelines.
AB  - Despite advancements in the treatment of early-stage breast cancer, many patients
      still develop disease recurrence; others present with de novo metastatic disease.
      For most patients with advanced breast cancer, the primary treatment intent is
      noncurative-that is, palliative-in nature. The goals of treatment should
      therefore focus on maximizing symptom control and extending survival. Treatments
      should be evaluated on an individualized basis in terms of evidence, but also
      with full respect for the wishes of the patient in terms of acceptable toxicity.
      Given the availability of extensive reviews on the roles of endocrine therapy and
      her2 (human epidermal growth factor receptor 2)-targeted therapies for advanced
      disease, we focus here mainly on treatment guidelines for the non-endocrine
      management of her2-negative advanced breast cancer in a Canadian health care
      context. 

PMID- 25848338
TI  - A Canadian national expert consensus on neoadjuvant therapy for breast cancer:
      linking practice to evidence and beyond.
AB  - BACKGROUND: Use of the neoadjuvant approach to treat breast cancer patients has
      increased since the early 2000s, but the overall pathway of care for such
      patients can be highly variable. The aim of our project was to establish a
      multidisciplinary consensus among clinicians with expertise in neoadjuvant
      therapy (nat) for breast cancer and to determine if that consensus reflects
      published methods used in randomized controlled trials (rcts) in this area.
      METHODS: A modified Delphi protocol, which used iterative surveys administered to
      85 experts across Canada, was established to obtain expert consensus concerning
      all aspects of the care pathway for patients undergoing nat for breast cancer.
      All rcts published between January 1, 1967, and December 1, 2012, were
      systematically reviewed. Data extracted from the rcts were analyzed to determine
      if the methods used matched the expert consensus for specific areas of nat
      management. A scoring system determined the strength of the agreement between the
      literature and the expert consensus. RESULTS: Consensus was achieved for all
      areas of the pathway of care for patients undergoing nat for breast cancer, with
      the exception of the role of magnetic resonance imaging in the pre-treatment or
      preoperative setting. The levels of agreement between the consensus statements
      and the published rcts varied, primarily because specific aspects of the pathway
      of care were not well described in the reviewed literature. CONCLUSIONS: A true
      consensus of expert opinion concerning the pathway of care appropriate for
      patients receiving nat for breast cancer has been achieved. A review of the
      literature illuminated gaps in the evidence about some elements of nat
      management. Where evidence is available, agreement with expert opinion is strong
      overall. Our study is unique in its approach to establishing consensus among
      medical experts in this field and has established a pathway of care that can be
      applied in practice for patients receiving nat.

PMID- 25848339
TI  - Locoregional therapy of locally advanced breast cancer: a clinical practice
      guideline.
AB  - QUESTIONS: In female patients with locally advanced breast cancer (labc) and good
      response to neoadjuvant chemotherapy (nact), including endocrine therapy, what is
      the role of breast-conserving surgery (bcs) compared with mastectomy?In female
      patients with labc, is radiotherapy (rt) indicated for those who have undergone
      mastectomy?does locoregional rt, compared with breast or chest wall rt alone,
      result in a higher survival rate and lower recurrence rates?is rt indicated for
      those achieving a pathologic complete response (pcr) to nact?In female patients
      with labc who receive nact, is the most appropriate axillary staging procedure
      sentinel lymph node biopsy (slnb) or axillary dissection? Is slnb indicated
      before nact rather than at the time of surgery?How should female patients with
      labc that does not respond to initial nact be treated? METHODS: This guideline
      was developed by Cancer Care Ontario's Program in Evidence-Based Care (pebc) and
      the Breast Cancer Disease Site Group (dsg). A systematic review was prepared
      based on literature searches conducted using the medline and embase databases for
      the period 1996 to December 11, 2013. Guidelines were located from that search
      and from the Web sites of major guideline organizations. The working group
      drafted recommendations based on the systemic review. The systematic review and
      recommendations were then circulated to the Breast Cancer dsg and the pebc Report
      Approval Panel for internal review; the revised document underwent external
      review. The full three-part evidence series can be found on the Cancer Care
      Ontario Web site. RECOMMENDATIONS: For most patients with labc, modified radical
      mastectomy should be considered the standard of care. For some patients with
      noninflammatory labc, bcs can be considered on a case-by-case basis when the
      surgeon deems that the disease can be fully resected and the patient expresses a
      strong preference for breast preservation.For patients with labc, rt after
      mastectomy is recommended.It is recommended that, after bcs or mastectomy,
      patients with labc receive locoregional rt encompassing the breast or chest wall
      and local node-bearing areas.It is recommended that postoperative rt remain the
      standard of care for patients with labc who achieve pcr to nact.It is recommended
      that axillary dissection remain the standard of care for axillary staging in
      labc, with the judicious use of slnb in patients who are advised of the
      limitations of the current data.Although slnb either before or after nact is
      technically feasible, the data are insufficient to make any recommendation about
      the optimal timing of slnb with respect to nact. Limited data suggest higher
      sentinel lymph node identification rates and lower false negative identification
      rates when slnb is conducted before nact; however, those data must be balanced
      against the requirement for two operations if slnb is not performed at the time
      of resection of the main tumour.It is recommended that patients receiving
      neoadjuvant anthracycline-taxane-based therapy (or other sequential regimens)
      whose tumours do not respond to the initial agent or agents, or who experience
      disease progression, be expedited to the next agent or agents of the regimen.For
      patients who, in the opinion of the treating physician, fail to respond or
      progress on first-line nact, several therapeutic options can be considered,
      including second-line chemotherapy, hormonal therapy (if appropriate), rt, or
      immediate surgery (if technically feasible). Treatment should be individualized
      through discussion at a multidisciplinary case conference, considering tumour
      characteristics, patient factors and preferences, and risk of adverse effects.It
      is recommended that prospective randomized clinical trials be designed for
      patients with labc who fail to respond to nact so that more definitive treatment
      recommendations can be developed.

PMID- 25848341
TI  - The best available evidence ... all in one place.

PMID- 25848340
TI  - Optimal systemic therapy for early breast cancer in women: a clinical practice
      guideline.
AB  - The Breast Cancer Disease Site Group of Cancer Care Ontario identified the need
      for new guidelines for the adjuvant systemic therapy of early-stage breast
      cancer. The specific question to be addressed was "What is the optimal adjuvant
      systemic therapy for female patients with early-stage operable breast cancer,
      when patient and disease factors are considered?" A systematic review was
      prepared based on literature searches conducted using the medline and embase
      databases for the period January 2008 to March 5, 2012, and updated to May 12,
      2014. Guidelines were located from that search, from the Standards and Guidelines
      Evidence directory of cancer guidelines, and from the Web sites of major
      guideline organizations. The literature located was subdivided into the broad
      categories of chemotherapy, hormonal therapy, and therapy targeted to her2 (human
      epidermal growth factor receptor 2). Although several of the systemic therapies
      discussed in this guideline can be considered in the neoadjuvant setting, the
      review focused on trials with rates of disease-free and overall survival as
      endpoints and thus excluded several trials that used pathologic complete response
      as a primary endpoint. Based on the systematic review, the working group drafted
      recommendations on the use of chemotherapy, hormonal therapy, and targeted
      therapy; based on their professional experience, they also drafted
      recommendations on patient and disease characteristics and recurrence risk. The
      literature review and draft recommendations were circulated to a consensus panel
      of medical oncologists who had expertise in breast cancer and who represented the
      regions of Ontario. Items without initial consensus were discussed at an in
      person consensus meeting held in Toronto, November 23, 2012. The final
      recommendations are those for which consensus was reached before or at the
      meeting. Some of the key evidence was revised after the updated literature
      search. Evidence reviews for systemic chemotherapy, endocrine therapy, and
      targeted therapy for her2-positive disease are reported in separate articles in
      this supplement. The full three-part 1-21 evidence-based series, including
      complete details of the development and consensus processes, can be found on the
      Cancer Care Ontario Web site at
      https://www.cancercare.on.ca/toolbox/qualityguidelines/diseasesite/breast-ebs. 

PMID- 25848342
TI  - Outcome of patients with pregnancy during or after breast cancer: a review of the
      recent literature.
AB  - BACKGROUND: An increasing number of young women are delaying childbearing; hence,
      more are diagnosed with breast cancer (bca) before having a family. No clear
      recommendations are currently available for counselling such a population on the
      safety of carrying a pregnancy during bca or becoming pregnant after treatment
      for bca. METHODS: Using a Web-based search of PubMed we reviewed the recent
      literature about bca and pregnancy. Our objective was to report outcomes for
      patients diagnosed with bca during pregnancy, comparing them with outcomes for
      non-pregnant women, and to evaluate prognosis in women diagnosed with and treated
      for bca who subsequently became pregnant. RESULTS: "Pregnancy and bca" should be
      divided into two entities. Pregnancy-associated bca tends to be more aggressive
      and advanced in stage at diagnosis than bca in control groups; hence, it has a
      poorer prognosis. With respect to pregnancy after bca, there is, despite the bias
      in reported studies and meta-analyses, no clear evidence for a different or worse
      disease outcome in bca patients who become pregnant after treatment compared with
      those who do not. CONCLUSIONS: Pregnancy-associated bca should be treated as
      aggressively as and according to the standards applicable in nonpregnant women;
      pregnancy after bca does not jeopardize outcome. The guidelines addressing risks
      connected to pregnancy and bca lack a high level of evidence for better
      counselling young women about pregnancy considerations and preventing unnecessary
      abortions. Ideally, evidence from large prospective randomized trials would set
      better guidelines, and yet the complexity of such studies limits their
      feasibility.

PMID- 25848345
TI  - Robust estimation of marginal regression parameters in clustered data.
AB  - We develop robust methods for analyzing clustered data where estimation of
      marginal regression parameters is of interest. Inverse cluster size reweighting
      in the objective function to be minimized is incorporated to handle the issue of
      informative cluster size. Performance of the resulting estimators is studied by
      simulation. Large sample inference and variance estimation is carried out. The
      methodology is illustrated using a periodontal disease dataset.

PMID- 25848343
TI  - Adjuvant chemotherapy for early female breast cancer: a systematic review of the
      evidence for the 2014 Cancer Care Ontario systemic therapy guideline.
AB  - BACKGROUND: The Program in Evidence-Based Care (pebc) of Cancer Care Ontario
      recently created an evidence-based consensus guideline on the systemic treatment
      of early breast cancer. The evidence for the guideline was compiled using a
      systematic review to answer the question "What is the optimal systemic therapy
      for patients with early-stage, operable breast cancer, when patient and disease
      factors are considered?" The question was addressed in three parts: cytotoxic
      chemotherapy, endocrine treatment, and human epidermal growth factor receptor 2
      (her2)-directed therapy. METHODS: For the systematic review, the medline and
      embase databases were searched for the period January 2008 to May 2014. The
      Standards and Guidelines Evidence directory of cancer guidelines and the Web
      sites of major oncology guideline organizations were also searched. The basic
      search terms were "breast cancer" and "systemic therapy" (chemotherapy, endocrine
      therapy, targeted agents, ovarian suppression), and results were limited to
      randomized controlled trials (rcts), guidelines, systematic reviews, and meta
      analyses. RESULTS: Several hundred documents that met the inclusion criteria were
      retrieved. The Early Breast Cancer Trialists' Collaborative Group meta-analyses
      encompassed many of the rcts found. Several additional studies that met the
      inclusion criteria were retained, as were other guidelines and systematic
      reviews. Chemotherapy was reviewed mainly in three classes: anti-metabolite-based
      regimens (for example, cyclophosphamide-methotrexate-5-fluorouracil),
      anthracyclines, and taxane-based regimens. In general, single-agent chemotherapy
      is not recommended for the adjuvant treatment of breast cancer in any patient
      population. Anthracycline-taxane-based polychemotherapy regimens are, overall,
      considered superior to earlier-generation regimens and have the most significant
      impact on patient survival outcomes. Regimens with varying anthracycline and
      taxane doses and schedules are options; in general, paclitaxel given every 3
      weeks is inferior. Evidence does not support the use of bevacizumab in the
      adjuvant setting; other systemic therapy agents such as metformin and vaccines
      remain investigatory. Adjuvant bisphosphonates for menopausal women will be
      discussed in later work. CONCLUSIONS: The results of this systematic review
      constitute a comprehensive compilation of the high-level evidence that is the
      basis for the 2014 pebc guideline on systemic therapy for early breast cancer.
      Use of cytotoxic chemotherapy is presented here; the results addressing endocrine
      therapy and her2-targeted treatment, and the final clinical practice
      recommendations, are published separately in this supplement.

PMID- 25848346
TI  - Epidemiology and Clinical Research Design, Part 1: Study Types.
AB  - Selecting the best available preventive and therapeutic measures to avoid
      disability and death is an important goal for all health care practitioners. To
      achieve this goal, we need to perform studies that determine the value of these
      measures. In this article, we discuss the possible study designs that can be used
      for evaluating new approaches to prevention and treatment. The gold standard
      study design is a randomized, controlled, double-blind trial. In many instances,
      a randomized controlled trial may not be ethically or practically feasible. Other
      study types, such as case series, case-control studies, cohort studies, cross
      sectional studies, crossover designs, and open-label studies, may be required to
      hypothesize and evaluate the link between an exposure or predictor variable and
      an outcome variable. Various study types pertaining to neonatal-perinatal
      medicine are reviewed in this article.

PMID- 25848344
TI  - Adjuvant endocrine therapy for early breast cancer: a systematic review of the
      evidence for the 2014 Cancer Care Ontario systemic therapy guideline.
AB  - BACKGROUND: Cancer Care Ontario's Program in Evidence-Based Care (pebc) recently
      created an evidence-based consensus guideline on the systemic treatment of early
      breast cancer. The evidence for the guideline was compiled using a systematic
      review to answer the question "What is the optimal systemic therapy for patients
      with early-stage, operable breast cancer, when patient and disease factors are
      considered?" The question was addressed in three parts: cytotoxic chemotherapy,
      endocrine treatment, and her2 (human epidermal growth factor receptor 2)-targeted
      therapy. METHODS: For the systematic review, the literature in the medline and
      embase databases was searched for the period January 2008 to May 2014. The
      Standards and Guidelines Evidence directory of cancer guidelines and the Web
      sites of major oncology guideline organizations were also searched. The basic
      search terms were "breast cancer" and "systemic therapy" (chemotherapy, endocrine
      therapy, targeted agents, ovarian suppression), and results were limited to
      randomized controlled trials (rcts), guidelines, systematic reviews, and meta
      analyses. RESULTS: Several hundred documents that met the inclusion criteria were
      retrieved. Meta-analyses from the Early Breast Cancer Trialists' Collaborative
      Group encompassed many of the rcts found. Several additional studies that met the
      inclusion criteria were retained, as were other guidelines and systematic
      reviews. SUMMARY: The results of the systematic review constitute a comprehensive
      compilation of high-level evidence, which was the basis for the 2014 pebc
      guideline on systemic therapy for early breast cancer. The review of the evidence
      for systemic endocrine therapy (adjuvant tamoxifen, aromatase inhibitors, and
      ovarian ablation and suppression) is presented here; the evidence for
      chemotherapy and her2-targeted treatment-and the final clinical practice
      recommendations-are presented separately in this supplement.

PMID- 25848347
TI  - Long-Term Response of Classic Kaposi's Sarcoma to Intralesional Doxorubicin: A
      Case Report.
AB  - Classic Kaposi's sarcoma (KS) is a disease with low mortality but high morbidity.
      The optimum treatment of KS depends upon several factors, including location of
      lesions, disease progression, severity of symptoms and patient preference. We
      report the long-term response to the use of intralesional doxorubicin to
      successfully treat a large cutaneous lesion of KS on a patient refractory to
      traditional treatments. 

PMID- 25848348
TI  - Basal cell carcinoma arising on a verrucous epidermal nevus: a case report.
AB  - We report a case of basal cell carcinoma that appeared from an epidermal
      verrucous nevus in a 61-year-old patient. The onset of basal cell carcinoma in
      sebaceous nevi, basal cell nevi and dysplastic nevi is relatively common, but it
      is rarely associated with epidermal verrucous nevi. There is no consensus on
      whether the two lesions have a common cellular origin or whether they merely
      represent a collision of two distinct tumors. Since this association - as with
      other malignant tumors - is rare, there is no need for prophylactic removal of
      epidermal verrucous nevi. 

PMID- 25848349
TI  - Perianal Basal cell carcinoma.
AB  - Basal cell carcinoma (BCC) is the most common non-melanoma skin cancer. Exposure
      to ultraviolet light is an important risk factor for BCC development and the
      disorder therefore develops commonly on body areas that are more exposed to
      sunlight, such as the face and neck. It is uncommon in the closed area of the
      body and quite rare in the perianal and genital regions. Herein, we report a 34
      year-old patient with perianal BCC who had no additional risk factors. 

PMID- 25848350
TI  - A Case of Old Age-Onset Generalized Pustular Psoriasis with a Deficiency of IL
      36RN (DITRA) Treated by Granulocyte and Monocyte Apheresis.
AB  - A 78-year-old woman who had been suffering from psoriasis vulgaris for 31 years
      was admitted to hospital because of her erythroderma. A toxic eruption was
      suspected and she was treated with prednisolone 30 mg daily. However, it was
      ineffective and, suspecting psoriatic erythroderma, cyclosporine 150 mg daily was
      administered with tapering of the prednisolone. Two weeks after a dose reduction
      of cyclosporine to 100 mg/day, erythroderma with widespread generalized pustules
      and fever developed. Histology of a biopsy revealed inflammatory infiltrates in
      the skin with a spongiform pustule of Kogoj, which was consistent with
      generalized pustular psoriasis (GPP). Her pustules improved with additional
      etretinate 20 mg/day, but the erythroderma persisted and she consulted us. Three
      sessions of granulocyte and monocyte apheresis once weekly were effective for her
      condition and decreased her serum levels of IL-6 and IL-8. She had homozygous
      mutations of c.[28C>T] in IL36RN which cause p.[Arg10Ter]. She is the oldest
      reported case of GPP with a deficiency of interleukin-36 receptor antagonist
      (DITRA), although GPP in DITRA has been suggested to usually occur in younger
      cases with no pre-existing psoriasis vulgaris. 

PMID- 25848352
TI  - A case of contiguous primary hepatic marginal zone B-cell lymphoma and hemangioma
      ultimately diagnosed using contrast-enhanced ultrasonography.
AB  - Primary hepatic marginal zone B-cell malignant lymphoma of mucosa-associated
      lymphoid tissue (MALT lymphoma) is extremely rare. We present a case in which a
      lesion was diagnosed as 2 contiguous tumors (MALT lymphoma and hemangioma) using
      contrast-enhanced ultrasonography (US) with sonazoid. There has been no previous
      case of contiguous hepatic MALT lymphoma and hemangioma. The present case was a
      female with no medical history. We detected a snowman-like appearance, which was
      a tumor of 15 mm in diameter with hypo- and hyper-echogenicities in the lateral
      and medial parts, respectively, in the Couinaud's segment (S6) of the liver on
      US. The tumor appeared as a single lesion with a low-density area in the
      unenhanced phase and prolonged enhancement in the equilibrium phases on dynamic
      CT. On MRI, the whole lesion showed a low-intensity signal on T1-weighted
      imaging, but isointensity in the lateral part and high intensity in the medial
      part were seen on T2-weighted imaging. On contrast-enhanced US, the lateral
      hypoechoic region was homogenously hyperenhanced in the early vascular phase, and
      the contrast medium was washed out after about 30 s; in contrast, the medial
      hyperechoic region was gradually stained from the margin toward the central
      region. The tumor showed a defect in both hypo- and hyperechoic regions in the
      postvascular phase. Hemangioma was suspected for the medial part based on the
      typical image findings, but the lateral part was not given a diagnosis. Thus,
      surgical resection was performed. The medial part was a hemangioma, and the
      lateral part was a MALT lymphoma by histopathological findings. 

PMID- 25848351
TI  - How early can pancreatic cancer be recognized? A case report and review of the
      literature.
AB  - The early symptoms of pancreatic cancer are often very vague. They may precede
      the diagnosis by years and go unrecognized. This makes pancreatic cancer one of
      the cancers with the worst survival rates. The progression rate of the early
      phase might be slower than previously thought. Here, we report a case where
      symptoms, including thromboembolism and new-onset diabetes mellitus, preceded the
      diagnosis of pancreatic cancer by 6 years or longer. The awareness of the early
      symptoms of pancreatic cancer is required for being vigilant and further
      diagnostic tests. A simple clinical model utilizing certain risk factors and
      symptoms for pancreatic cancer will help stratify the patients for further
      screening tests. 

PMID- 25848354
TI  - Korean medicine therapy as a substitute for chemotherapy for metastatic breast
      cancer: a case report.
AB  - A 46-year-old Korean woman was diagnosed with stage III breast cancer and
      underwent 8 cycles of neoadjuvant chemotherapy, breast conservation surgery and
      adjuvant radiotherapy. However, the cancer recurred in the right upper lung (RUL)
      and the right pulmonary hilum after 8 months. The RUL nodule was removed through
      a wedge resection, and the pathologic finding was revealed as a metastatic
      adenocarcinoma. Adjuvant chemotherapy was recommended, but she refused it because
      she feared adverse reactions to chemotherapy. Instead, Korean Medicine Therapy
      with intravenous wild ginseng pharmacopuncture (WGP), Cordyceps sinensis
      pharmacopuncture, Trichosanthes kirilowii pharmacopuncture, Euonymus alatus
      pharmacopuncture (EAP) and Astragalus membranaceus pharmacopuncture was started.
      After a month, the disease looked stable, but findings of newly occurring
      metastatic lymphadenopathies appeared on CT after 6 months. Salvage chemotherapy
      was recommended, but she also refused it. At this time, Prunella vulgaris
      pharmacopuncture was started. Finally, a complete resolution was confirmed on PET
      CT after 5 months, and she has remained in stable condition for more than 6
      months with WGP, EAP, a Soram nebulizer solution inhalation and the oral intake
      of Soramdan S and Hangamdan S. 

PMID- 25848353
TI  - Multiple myeloma and atopic eczema in an adult.
AB  - Multiple myeloma is the fourteenth cause of cancer-related death. The symptoms of
      myeloma are mostly nonspecific, and there is significant delay between the first
      symptoms and diagnosis of myeloma. Atopic eczema is a common chronic inflammatory
      skin disease associated with dysregulation of the immune system. It generally
      develops in early childhood but can also occur in adults. Eczema is associated
      with a variety of hematological and solid malignancies, and possibly multiple
      myeloma. We report a patient with eczema that developed 5 years before the
      diagnosis of multiple myeloma but was mistaken for psoriasis. 

PMID- 25848355
TI  - Prolonged Response and Restoration of Functional Independence with Bevacizumab
      plus Vinorelbine as Third-Line Treatment for Breast Cancer-Related Leptomeningeal
      Metastases.
AB  - BACKGROUND: Survival of patients with leptomeningeal metastases (LM) and impaired
      functional status is limited to several months, and rarely does neurological
      function improve with treatment. CASE REPORT: A 34-year-old female with hormone
      negative and HER2-positive metastatic breast cancer was diagnosed with bulky
      radiographic LM 45 months after initial diagnosis. She was treated with intra-CSF
      trastuzumab followed by intra-CSF liposomal cytarabine; however, the cancer
      progressed 8 months after the diagnosis of LM. At the time of the third LM
      progression, the patient presented with a cauda equina syndrome and cerebellar
      impairment resulting in an inability to walk. She was treated with CNS-directed
      radiotherapy (lumbosacral and cerebellar) and bevacizumab plus vinorelbine. Rapid
      functional improvement occurred, and the patient regained the ability to walk and
      independently manage her daily activities. Twelve months later, she presented
      with rapid progression of the LM resulting in death within several weeks.
      CONCLUSION: In radiographically defined bulky LM, the combination of systemic
      therapy and CNS-directed radiotherapy likely is more active than intra-CSF
      therapy only. In lieu of the rapid and significant improvement in neurological
      function combined with the prolonged response, bevacizumab alone or in
      combination with chemotherapy and CNS-directed radiotherapy may be considered in
      select patients with radiographically bulky breast cancer-related LM.

PMID- 25848356
TI  - Pharmacokinetics of gefitinib in a patient with non-small cell lung cancer
      undergoing continuous ambulatory peritoneal dialysis.
AB  - A 72-year-old man undergoing continuous ambulatory peritoneal dialysis (CAPD) for
      chronic renal failure and who had undergone right upper lobectomy for lung
      adenocarcinoma (pT2aN0M0) 2 years ago was admitted for recurrence of lung cancer
      presenting as multiple brain metastases. An epidermal growth factor receptor
      mutation analysis of his lung cancer revealed a deletion of 15 nucleotides (E746
      A750) in exon 19. After whole-brain radiotherapy, we started daily administration
      of 250 mg gefitinib under the continuation of CAPD and performed a
      pharmacokinetic analysis. We speculated that the plasma concentration of
      gefitinib reached the steady state at least by day 16 after the start of
      gefitinib (626.6 ng/ml at trough level). On day 46, the plasma concentration was
      538.4 ng/ml at trough level and the concentration in the peritoneal dialysis
      fluid was 34.6 ng/ml, suggesting that CAPD appeared to have little effect on the
      pharmacokinetics of gefitinib. During gefitinib therapy, there were no
      significant adverse events except for grade 2 diarrhea. Gefitinib could be safely
      administered to a patient undergoing CAPD. 

PMID- 25848357
TI  - Clinical Response to Sorafenib in a Patient with Metastatic Colorectal Cancer and
      FLT3 Amplification.
AB  - BACKGROUND: A considerable number of patients with metastatic colorectal cancer
      progress after exhausting all approved standard therapies but maintain an
      adequate performance status and could be candidates for further treatment. We aim
      at reviewing our experience with sorafenib treatment of a patient with FLT3
      mutation in refractory metastatic colorectal cancer. METHODS: Treatment with
      sorafenib of a patient with metastatic colorectal cancer and FLT3 translocation
      who had previously been heavily treated. RESULTS: The patient with metastatic
      colorectal cancer, aged 51 years, showed significant symptomatic and laboratory
      improvement with sorafenib treatment (400 mg twice daily). CONCLUSION: The
      presented case illustrates how an aggressive and refractory colorectal tumor may
      respond well to targeted therapy.

PMID- 25848358
TI  - Tyrosine kinase inhibitor induced isolated pericardial effusion.
AB  - Long-term therapy with tyrosine kinase inhibitors (TKI) has resulted in improved
      outcomes for patients suffering from Bcr-Abl fusion protein-harboring leukemias.
      As a result, a growing population of patients on TKI therapy present to their
      primary care providers. In this case, we report on the case of a 62-year-old male
      who presented with a symptomatic pericardial effusion. After pericardiocentesis,
      malignancy and infectious etiologies were excluded. The pericardial effusion was
      attributed to his TKI, with a transition of this medication to a different TKI. A
      repeat evaluation 1 month following the withdrawal of the offending agent showed
      no recurrence of his pericardial effusion on echocardiogram. In this report, we
      will highlight a rare but important side effect of TKI therapy before discussing
      its purported mechanisms and differing incidence rates. Early recognition of
      serosal inflammation related to long-term TKI therapy by primary care providers
      is important in preventing patient morbidity and mortality. 

PMID- 25848359
TI  - Spontaneous regression of hepatocellular carcinoma: its imaging course leading to
      complete disappearance.
AB  - Spontaneous regression of hepatocellular carcinoma (HCC) is a rare phenomenon. We
      followed a detailed clinical course of a spontaneous and complete disappearance
      of HCC during a short interval. A 73-year-old man with hepatitis B virus
      infection presented with a 15-mm mass in the right anterior superior segment of
      the liver. The mass was diagnosed as HCC by imaging findings. We found an
      elevated serum alpha-fetoprotein (AFP) level of 748 ng/ml. The tumor regressed to
      6 mm on imaging examination, and the AFP serum level decreased to 87.8 ng/ml 1
      month after the diagnostic hepatic angiography. Therefore, the patient was
      followed up without any treatment for HCC. The tumor disappeared 5 months later
      when the AFP serum level was 5.0 ng/ml. The diagnostic hepatic angiography might
      have had some effect on the spontaneous regression of HCC in the present case. 

PMID- 25848360
TI  - A Case of Disease Improvement after Treatment with Everolimus plus Exemestane in
      a Patient with Hormone Receptor-Positive Metastatic Breast Cancer with Bone
      Metastases.
AB  - Breast cancer is one of the most frequently diagnosed cancers and a leading cause
      of death in women worldwide. Despite significant advances in the treatment of
      hormone receptor-positive breast cancer, tumor metastasis occurs frequently and
      is associated with poor long-term prognosis. The mammalian target of rapamycin
      (mTOR) pathway plays a central role in cancer cell growth, proliferation, and
      resistance to endocrine therapies. Therefore, mTOR inhibitors such as everolimus
      in combination with nonsteroidal aromatase inhibitors might reverse endocrine
      resistance and improve clinical outcomes in patients. Here, we report on a case
      of infiltrating lobular carcinoma of the breast with metastases to the bone.
      Histopathologic analysis showed that the patient was estrogen and progesterone
      receptor positive and human epidermal growth factor-2 negative. This case
      represents the clinical spectrum of complications caused by metastasis: the
      patient experienced a considerable amount of skeletal-related complications, had
      previously received chemotherapy, and experienced disease progression while
      taking nonsteroidal aromatase inhibitors. After treatment with oral everolimus 10
      mg daily plus oral exemestane 25 mg daily, the patient's disease was ameliorated.
      Combination therapy was well tolerated, with minimal adverse effects that were
      manageable with concomitant medications. Although further analyses in larger
      populations are necessary, the addition of everolimus to exemestane might provide
      an effective new treatment option for patients with bone metastasis. 

PMID- 25848361
TI  - Sebaceous carcinoma of the parotid gland: a case report.
AB  - BACKGROUND: Primary sebaceous carcinoma of the parotid gland is extremely rare,
      and because of its rarity, clinicopathological characteristics and histogenesis
      are not fully understood. METHODS: Here, we report a patient who presented with a
      left infra-auricular painless mass. We present the histological features and
      discuss possible optimal treatments based on previous literature. RESULTS: The
      mass was suspected to be a myoepithelial tumor or possibly a pleomorphic adenoma.
      Initially, the mass was resected with preservation of the facial nerve, but this
      caused facial palsy. Because the histological examination showed a sebaceous
      carcinoma and a part of the mass could be remaining on the facial nerve,
      additional surgery was performed, and the facial nerve was reconstructed with
      cervical nerve. Follow-up after 7 months showed no sign of recurrence of
      metastasis. CONCLUSION: We encountered a rare sebaceous carcinoma of the parotid
      gland. Additional surgery was performed because preoperative diagnosis was
      difficult.

PMID- 25848362
TI  - Balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension.

PMID- 25848363
TI  - How to walk the tightrope between harm and protection in selecting the optimal
      antiplatelet treatment strategy after transcatheter left atrial appendage
      occlusion.

PMID- 25848364
TI  - Non-ST elevation myocardial infarction related to total coronary artery occlusion
      - prevalence and patient characteristics.
AB  - INTRODUCTION: Acute coronary occlusion (ACO) may also present as non-ST elevation
      myocardial infarction (NSTEMI) and thus veil the real threat. AIM: Based on
      combined analysis of electrocardiography and echocardiography findings, we aimed
      to describe profile of NSTEMI patients at increased risk of ACO. MATERIAL AND
      METHODS: It was a retrospective study that included patients referred for cardiac
      catheterisation due to NSTEMI. Patients were selected into the study in two
      different time frames. Firstly, all consecutive NSTEMI patients were enrolled in
      a 12-month period to detect the prevalence of ACO (prevalence group). Secondly,
      all NSTEMI patients with ACO hospitalized in the previous 5 years were also
      enrolled (NSTEMI-ACO group). All patients had 12-lead electrocardiogram (ECG) and
      the transthoracic echocardiography (TTE) performed before the cardiac
      catheterisation. RESULTS: Fifty-three consecutive patients (37 males) were
      enrolled into the prevalence group in a 12-month period. Ten (19%) of them were
      diagnosed with ACO. Thirty-four consecutive patients were enrolled into the
      NSTEMI-ACO group. Non-ST elevation myocardial infarction patients with ACO were
      younger as compared to NSTEMI patients without ACO. Non-ST elevation myocardial
      infarction patients with ACO were less likely to have anterior wall ischaemia as
      detected by ECG, which was not reflected by TTE results. Combined assessment of
      ischaemia by ECG and impaired contractility by TTE did not reveal any significant
      differences between NSTEMI patients with or without ACO. CONCLUSIONS: The
      identification of NSTEMI patients with ACO is challenging. Therefore, the utmost
      caution should be paid to prevent delay of coronary angiography in NSTEMI
      patients who have increased risk of ACO.

PMID- 25848365
TI  - Percutaneous closure of the left atrial appendage for secondary prevention of
      stroke in patients with atrial fibrillation and contraindications to chronic
      anticoagulant therapy.
AB  - INTRODUCTION: Stroke accounts for approx. 90% of thromboembolic complications
      associated with atrial fibrillation. The use of oral anticoagulants is the most
      effective therapy but is associated with risk of haemorrhagic complications. AIM:
      In this article, we describe a series of patients with atrial fibrillation,
      cardiogenic stroke history, and contraindications for long-term anticoagulant
      therapy, in whom an alternative method - percutaneous closure of the left atrial
      appendage - was performed. MATERIAL AND METHODS: Nine patients with atrial
      fibrillation and previous stroke were qualified for percutaneous closure of the
      left atrial appendage (5 men and 4 women, aged 45-78 years). Physical and
      neurological examinations were conducted in the qualification period, 1-3 days
      before the intervention, and 1-3 days and 1, 3, 6, 12, and 24 months following
      percutaneous closure of the left atrial appendage. Transoesophageal
      echocardiography was carried out in the qualification period, 1-3 days before the
      intervention, and at 1-3 days and 3 and 6 months following the procedure.
      RESULTS: No complications were observed in the perioperative period and during
      the follow-up period of 16-31 months. Echocardiographic examinations showed that
      occluders were present in the appropriate positions. CONCLUSIONS: Percutaneous
      closure of the left atrial appendage can be an alternative form of secondary
      prevention of stroke in patients with atrial fibrillation and contraindications
      for long-term anticoagulant therapy or those who have problems managing drug
      treatment. Complex clinical assessment performed by a neuro-cardiac team allows
      safe and efficient invasive treatment.

PMID- 25848366
TI  - Antiplatelet resistance and the role of associated variables in stable patients
      treated with stenting.
AB  - INTRODUCTION: Nowadays, clopidogrel and acetylsalicylic acid (ASA) have become
      routinely applied therapies in percutaneous coronary interventions (PCI) with
      stenting. AIM: Numerous variables can interfere with antiplatelet responsiveness,
      so we aimed to investigate the role of different variables associated with ASA or
      clopidogrel resistance in stable coronary artery disease. MATERIAL AND METHODS: A
      total of 207 patients undergoing elective PCI were included in the analysis. All
      patients received a loading dose of clopidogrel and ASA during PCI procedure and
      followed by dual antiplatelet therapy. Clopidogrel and ASA resistance were
      measured by impedance aggregometry method. RESULTS: Of the patients, 19.8% had
      clopidogrel resistance, 18.8% had ASA resistance, 9.2% had both clopidogrel and
      ASA resistance, and 71.5% were responsive to both drugs. In multivariate
      analysis, platelet count, angiotensin receptor blocker (ARB) use, and ASA
      resistance were independent variables associated with clopidogrel resistance, and
      clopidogrel resistance was the only variable associated with ASA resistance. In
      differentiating whether clopidogrel resistance exists or not, optimum ASA
      aggregometry response cut-off values were specified, and in differentiating
      whether ASA resistance exists or not, optimum clopidogrel aggregometry response
      cut-off values were specified. CONCLUSIONS: In this study, there was a higher
      incidence of low responsiveness to ASA when there was a low response to
      clopidogrel, and vice versa. Angiotensin receptor blocker use, platelet count,
      and ASA resistance were independent variables associated with clopidogrel
      resistance. Clopidogrel resistance was the only independent variable associated
      with ASA resistance. Angiotensin receptor blocker use seems to an independent
      risk factor for clopidogrel resistance in this study, but this result needs to be
      verified in other studies.

PMID- 25848367
TI  - The relationship between rheumatoid factor levels and coronary artery lesion
      complexity and severity in patients with stable coronary artery disease.
AB  - INTRODUCTION: The relation between serum rheumatoid factor levels and the extent,
      severity, and complexity of coronary artery disease has not been adequately
      studied. AIM: Therefore, we assessed the relationship between the severity of
      coronary artery disease assessed by SYNTAX score and serum rheumatoid factor
      levels in patients with stable coronary artery disease. MATERIAL AND METHODS: We
      enrolled 268 consecutive patients who underwent coronary angiography. Patients
      with acute coronary syndrome and chronic immune disorders were excluded. Baseline
      serum rheumatoid factor levels were measured and the SYNTAX score was calculated
      from the study population. RESULTS: Patients were divided into two groups. Group
      1 was defined as low SYNTAX score < 22, and group 2 was defined as intermediate
      and high SYNTAX score > 22. Serum rheumatoid factor levels were significantly
      higher in the intermediate and high-SYNTAX score group than in the low-SYNTAX
      score group (16.4 +/-9 IU/mlvs. 11.36 +/-5 IU/ml, p < 0.001). Also, there was a
      significant correlation between rheumatoid factor and CRP levels with the SYNTAX
      score r = 0.411; p < 0.001 and r = 0.275; p < 0.001, respectively. On
      multivariate linear regression analysis, rheumatoid factor (beta = 0.101, p <
      0.001) was an independent risk factor for intermediate and high SYNTAX score in
      patients with stable coronary artery disease. In receiver operator characteristic
      curve analysis, optimal cut-off value of rheumatoid factor to predict high SYNTAX
      score was found to be 10.5 IU/ml, with 69% sensitivity and 61% specificity.
      CONCLUSIONS: The rheumatoid factor level was independently associated with the
      extent, complexity, and severity of coronary artery disease assessed by SYNTAX
      score in patients with stable coronary artery diseases.

PMID- 25848368
TI  - Transradial approach for vertebral artery stenting.
AB  - INTRODUCTUION: Symptomatic severe vertebral artery (VA) stenosis may be treated
      safely with stent supported angioplasty via femoral access. There is limited
      clinical data on transradial approach for VA angioplasty in case of peripheral
      artery disease. AIM: To evaluate the safety and efficacy of transradial
      angioplasty of symptomatic VA stenosis. MATERIAL AND METHODS: Fifteen patients
      (age 66 +/-7.4 years, 73% men, with VA > 80% stenosis, 11 right-side, all
      symptomatic from posterior circulation (history of stroke, TIA, or chronic
      ischaemia symptoms)) with peripheral artery disease (PAD) or unsuccessful attempt
      via femoral approach were scheduled for VA angioplasty by radial access. Clinical
      and duplex ultrasound (DUS) follow-up were performed before discharge and 1, 12,
      and 24 months after VA angioplasty. RESULTS: The technical success rate was 100%.
      In all cases VA angioplasty was performed with the use of single balloon-mounted
      stent (9 bare metal stents, 6 drug-eluting stents). The mean NASCET VA stenosis
      was reduced from 85.3% to 5.3% (p < 0.001). No periprocedural death, stroke,
      myocardial infarction, or transient ischaemic attack occurred. During 24-months
      follow-up, in 12 of 15 patients chronic ischaemia symptoms release was observed,
      and no new acute ischaemic neurological symptoms were diagnosed in all patients.
      One patient died 20 months after intervention from unknown causes. There was one
      symptomatic borderline VA in-stent stenosis 12 months after angioplasty.
      CONCLUSIONS: Transradial VA stenting may be a very effective and safe procedure,
      and it may constitute an alternative to the femoral approach in patients with
      symptomatic VA stenosis.

PMID- 25848370
TI  - Stenting of the right ventricular outflow tract in a symptomatic newborn with
      tetralogy of Fallot.
AB  - This case describes a successful percutaneous stent implantation to critical
      stenosis of the right ventricle outflow tract in a female neonate with tetralogy
      of Fallot. At the time of the procedure she had poor development of the pulmonary
      arteries (McGoon and Nakata index 1.45 and 120, respectively). Stent implantation
      ensured an immediate increase in oxygen saturation level, and the physiological
      pulsating blood inflow caused good development of the pulmonary arteries during
      12 months of follow up (McGoon 2.5; Nacata Index 436). After this time she was
      qualified for surgery and underwent surgical correction without using a patch or
      conduit implantation. 

PMID- 25848369
TI  - The impact of transcatheter aortic valve implantation on left ventricular
      performance and wall thickness - single-centre experience.
AB  - INTRODUCTION: Transcatheter aortic valve implantation (TAVI) is a treatment
      alternative for the elderly population with severe symptomatic aortic stenosis
      (AS) at high risk for surgical aortic valve replacement (SAVR). AIM: To assess
      the impact of TAVI on echocardiographic parameters of left ventricular (LV)
      performance and wall thickness in patients subjected to the procedure in a single
      centre between 2009 and 2013. MATERIAL AND METHODS: The initial group consisted
      of 170 consecutive patients with severe AS unsuitable for SAVR. Logistic European
      System for Cardiac Operative Risk Evaluation (EuroSCORE) was 21.73 +/-12.42% and
      mean age was 79.9 +/-7.5 years. RESULTS: The TAVI was performed in 167 (98.2%)
      patients. Mean aortic gradient decreased significantly more rapidly after the
      procedure (from 58.6 +/-16.7 mm Hg to 11.9 +/-4.9 mm Hg, p < 0.001). The LV
      ejection fraction (LVEF) significantly increased in both short-term and long-term
      follow-up (57 +/-14% vs. 59 +/-13%, p < 0.001 and 56 +/-14% vs. 60 +/-12%, p <
      0.001, respectively). Significant regression of interventricular septum diameter
      at end-diastole (IVSDD) and end-diastolic posterior wall thickness (EDPWth) was
      noted in early (15.0 +/-2.4 mm vs. 14.5 +/-2.3 mm, p < 0.001 and 12.7 +/-2.1 mm
      vs. 12.4 +/-1.9 mm, p < 0.028, respectively) and late post-TAVI period (15.1 +/
      2.5 mm to 14.3 +/-2.5 mm, p < 0.001 and 12.8 +/-2.0 mm to 12.4 +/-1.9 mm, p <
      0.007, respectively). Significant paravalvular leak (PL) was noted in 21 (13.1%)
      patients immediately after TAVI and in 13 (9.6%) patients in follow-up (p <
      0.001). Moderate or severe mitral regurgitation (msMR) was seen in 24 (14.9%)
      patients from the initial group and in 19 (11.8%) patients after TAVI (p <
      0.001). CONCLUSIONS: The TAVI had an immediate beneficial effect on LVEF, LV
      walls thickness, and the incidence of msMR. The results of the procedure are
      comparable with those described in other centres.

PMID- 25848371
TI  - Hybrid stent implantation to the pulmonary artery from peripheral access via
      recruited systemic-pulmonary shunt.
AB  - The implantation of vascular stents in patients with low body weight and
      difficult anatomy of the stenosis needs individual cannulation strategy or a
      hybrid approach. We present a successful balloon angioplasty with direct stent
      implantation to severe ostial stenosis of the left pulmonary artery to xenograft
      anastomosis (LPA) in a 6-year-old boy late after surgical correction of pulmonary
      atresia with ventricular septal defect. Peripheral approach to LPA was possible
      after surgical rethoracotomy and the recruitment of a left Blalock-Taussig (BT)
      shunt stump. The cooperation of cardiovascular intervention with surgical
      approach appears a safe strategy for borderline patients referred for staged
      treatment of complex congenital heart defects. 

PMID- 25848372
TI  - Stent loss in the radial artery - surgical vs. interventional approach - report
      of two cases.
AB  - Stent loss during coronary angioplasty is a complication that can be managed in
      various manners; however, transradial access limits the options available. We
      describe two coronary interventions complicated by stent dislodgement, initially
      managed by pulling the stent back to the radial artery. Both stents were
      unwillingly lost on different levels in radial arteries. The first case was
      managed with a direct radial artery cut-down because distal location made it a
      quick and straightforward procedure. In the second case a partially deployed
      stent was lost in the proximal part of the radial artery. It was rewired,
      deployed, and post-dilated with a larger balloon. This enabled continuation of
      the procedure using the same access. Both cases were asymptomatic during 24
      months of follow-up. It is crucial to avoid leaving artificial bodies in arteries
      supplying vital organs because stent-related thrombosis or stenosis may seriously
      compromise blood flow. Removing the stent via the introducer sheath should be
      considered the optimal treatment. Unfortunately it is common that a partially
      expanded stent will not pass through the sheath. The superficial location of the
      distal radial artery segment facilitates surgical cut-down with local
      anaesthesia. When dislodgement occurs in deeper segments of the radial artery,
      the benefits from cut-down seem to be less because the procedure might take more
      time and be more difficult - as in the presented case in which we decided to
      rewire and fully expand the stent in situ. Retrieval of the stent at all costs
      might have led to further complications; hence stent deployment may be a good
      alternative to retrieval in such cases. 

PMID- 25848373
TI  - Transfemoral transcatheter aortic valve implantation in a patient with a severe
      aortic stenosis and cardiogenic shock requiring intra-aortic balloon pump
      support.
AB  - The following paper presents a patient with severe aortic stenosis and severely
      reduced left ventricular ejection fraction with intra-aortic balloon pump
      counterpulsation support, who underwent transfemoral aortic valve implantation of
      a CoreValve prosthesis. 

PMID- 25848374
TI  - Knuckle technique guided by intravascular ultrasound for in-stent restenosis
      occlusion treatment.
AB  - One of the rarest lesions is in-stent restenosis chronic total occlusion (CTO).
      Limited data suggest that the treatment success rate is dependent on the
      possibility to cross into the lumen of an occluded stent, and the decision about
      what technique to use varies by operator preference. The knuckle technique is
      used to create a deliberate dissection plane in various CTO techniques. A guide
      wire is pushed until a complex loop is formed and advanced through the lesion. In
      this report we present a case where a knuckle wire guided by intravascular
      ultrasound control is used to penetrate the distal cap in an in-stent restenosis
      CTO lesion. 

PMID- 25848375
TI  - Catheter inside the right heart for 22 years: to intervene or not to intervene?
AB  - Treatment of a central venous catheter emboli that has been asymptomatic for a
      number of years is controversial. A 56-year-old male patient who had an operation
      for sinus Valsalva aneurism rupture 22 years ago was referred to cardiology
      department for routine control. He had a mass inside the right heart on
      echocardiographic examination, and computed tomography revealed that this mass
      was an embolic piece of catheter. Catheters that have stayed inside the heart for
      a long time are removed due to the risk of distal embolisation and endocarditis,
      but the risk of removal is not known. Non-invasive follow-up of asymptomatic
      patients is often preferred because of the stabilisation of the embolised
      catheter due to endothelisation and the risk of complications during removal.
      Treatment of patients with catheter-piece emboli who are asymptomatic should be
      individualised, taking into account the risk of thrombosis, arrhythmia, and
      infection. 

PMID- 25848376
TI  - Cutting balloon use may ease the optimal apposition of bioresorbable vascular
      scaffold in in-stent stenosis.
AB  - Bioresorbable vascular scaffolds (BVS) have different mechanical properties as
      compared to metallic stents. Therefore, the standard procedural technique to
      achieve appropriate deployment may differ. Utilisation of debulking techniques,
      including cutting balloon and directional atherectomy prior to BVS deployment, is
      still questionable. Herein, we discuss a case of coronary in-stent restenosis and
      reveal the advantage of predilatation of the lesion with cutting balloon prior to
      BVS deployment. 

PMID- 25848377
TI  - A unique case of systemic thromboembolism in a patient with arrhythmogenic right
      ventricular cardiomyopathy.
AB  - We report a case of a 37-year-old woman with arrhythmogenic right ventricular
      cardiomyopathy (ARVC), after implantation of a cardioverter-defibrillator (ICD),
      who was admitted to our hospital because of focal infarctions in the right kidney
      and in the spleen. Echocardiography showed thrombi on the ICD electrode and the
      presence of patent foramen ovale. Patent foramen ovale was successfully closed by
      septal occluder. To our knowledge it is the first ever case report of paradoxical
      thromboembolism in a patient with ARVC. 

PMID- 25848378
TI  - Left circumflex coronary artery occlusion due to a left atrial appendage closure
      device.
AB  - Nowadays, percutaneous left atrial appendage (LAA) closure is spreading, and a
      large number of patients with this procedure have concomitant coronary artery
      disease. With the presented case it could be concluded that coronary angiography
      is recommended before LAA closure. 

PMID- 25848379
TI  - Emerging Intestinal Microsporidia Infection in HIV(+)/AIDS Patients in Iran:
      Microscopic and Molecular Detection.
AB  - BACKGROUND: Species of Microsporidia have been known as opportunistic obligate
      intracellular parasites particularly in immunocompromised patients.
      Enterocytozoon bieneusi is one of most prevalent intestinal microsporida
      parasites in HIV(+)/AIDS patients. In this study, intestinal microsporidia
      infection was determined in HIV(+)/AIDS patients using microscopic and molecular
      methods. METHODS: Stool samples were collected from HIV(+)/AIDS patients during
      12 months. All of the stool specimens washed with PBS (pH: 7.5). Slim slides were
      prepared from each sample and were examined using light microscope with 1000X
      magnification. DNA extraction carried out in microscopic positive samples. DNA
      amplification and genus/species identification also performed by Nested-PCR and
      sequencing techniques. RESULTS: From 81 stool samples, 25 were infected with
      microsporidia species and E. bieneusi were identified in all of positive samples.
      No Encephalitozoon spp. was identified in 81 collected samples using specific
      primers. CONCLUSION: E. bieneusi is the most prevalent intestinal microsporidia
      in immunocompromised patients of Iran. On the other hand, Nested-PCR using
      specific primers for ssu rRNA gene is an appropriate molecular method for
      identification of E. bieneusi.

PMID- 25848380
TI  - An Analysis of Clinical Characteristics of Strongyloides stercoralis in 70
      indigenous patients in Iran.
AB  - BACKGROUND: Clinical manifestations of Strongyloides stercoralis are variable
      from asymptomatic to hyperinfection and devastating disseminated infections.
      Hereby, clinical characteristics of a large series of Iranian strongyloidiasis
      indigenous cases are described. METHODS: The records of people referred to the
      Helminthological Diagnostic Laboratory of School of Public Health, Tehran
      University of Medical Sciences and School of Medicine, Gilan University of
      Medical Sciences, during 2009-2013 were reviewed. For those patients that were
      infected with S. stercoralis and their clinical manifestations and demographic
      data were available (70 cases) a checklist was prepared and data analyzed.
      RESULTS: Forty-three patients (61.4%) were male and 27 (38.6%) female.
      Gastrointestinal, cutaneous and pulmonary symptoms were present in 71.4%, 25.7%,
      and 15.7% of patients, respectively. None of them had larva currens eruption.
      Eosinophilia was the most prevalent reason for suspicious on S. stercoralis, but
      the mean was lower in elderly patients. Hyperinfection were recorded in 8
      patients (11.4%), and 2 cases had disseminated infection. CONCLUSION:
      Eosinophilia is common both in asymptomatic and symptomatic cases of
      strongyloidiasis, but the mean tend to lower with increase in age.

PMID- 25848381
TI  - Canine Babesiosis in China Caused by Babesia gibsoni: A Molecular Approach.
AB  - BACKGROUND: To provide a point of reference to study the epidemiology and
      clinical expression of canine babesiosis in China. METHODS: A total of 30 dogs
      infected with canine babesiosis were evaluated by mean of clinical history,
      physical examination, hematological, restriction fragment length polymorphism of
      PCR products (PCR-RFLP) and sequencing analysis. RESULT: The most prevalent
      clinical abnormalities were lethargy (100%), anorexia (100%), pale or icteric
      mucous membranes (80%), fever (70%) and dark urine (70%). Hematology parameters
      revealed that anemia and thrombocytopenia were the major abnormalities in blood
      of dogs infected with canine babesia. The results of PCR-RFLP and sequencing
      analysis indicated that B. gibsoni was the main species responsible for canine
      babesiosis cases at the time of the study in Nanjing, China. CONCLUSIONS: The
      results provide valuable information for better understanding of the epidemiology
      of canine babesiosis in China.

PMID- 25848382
TI  - Epidemiology, sero-diagnosis and therapeutic studies on nematodes infection in
      balochi range-sheep at district quetta, balochistan, pakistan.
AB  - BACKGROUND: Among the infectious organisms of parasitic origin, gastrointestinal
      nematodes are very important as they have been reported worldwide. The main aim
      of the present research study to highlight the annual epidemiological
      contributing factors associated with the prevalence of gastrointestinal nematodes
      and their control in sheep. METHODS: A total 1200 faecal samples (100 per month)
      were collected from farmers holding Balochi-sheep (either sexes, 1-5 years old)
      during January-December 2012 and analyzed to determine the prevalence of
      nematodes based on microscopy and ELISA based diagnostic assay. Therapeutic
      efficacies of different synthetic and herbal medicines against these nematodes
      were assessed by field trials. RESULTS: Results showed that 23.92% Balochi-sheep
      were infected with nematodes. Five nematodes infections were recorded with
      highest prevalence of Haemonchus (7.75%) followed by Nematodirus (7.58%),
      Strongyloides (4.42%), Trichostrongylus (2.33%) and Trichuris (1.83%). The
      younger and older ewes (one and five years) presented higher nematodes prevalence
      with peak during March/April and August/September. Haemonchus and Trichuris
      positive samples based on coprological examination were also showed 92-100%
      positive sensitivity for these nematodes by the ELISA. Sheep treated with
      Ivermectin showed higher reduction (97.76%) in nematode egg counts followed by
      Atreefal deedan (96.42%) and Oxfendazole (95.44%), respectively. CONCLUSION: The
      gastro-intestinal nematodes are prevalent in all age and either sex of Balochi
      sheep with peak during summer. The ELISA based diagnosis is more accurte. The
      synthetic and herbal products are very effective against sheep nematodes.

PMID- 25848383
TI  - Seroprevalence of Toxoplasma gondii Infections in Pregnant Women in Gorgan City,
      Golestan Province, Northern Iran-2012.
AB  - BACKGROUND: Toxoplasma gondii is one of the most prevalent parasites of human and
      warm- blooded animals. Toxoplasmosis is important especially in two groups:
      pregnant women and immunocompromised patients. If women acquire the primary
      infection during the pregnancy, it would be life threatening or remains severe
      disorders for the fetus. This study was performed to evaluate the seroprevalence
      of T. gondii infection in pregnant women referred to Health Center in Gorgan
      City, Golestan Province, northern Iran. METHODS: Serum samples were collected
      from pregnant women referred to Health Center in Gorgan City, south eastern
      Caspian Sea. Anti- Toxoplasma IgG and IgM antibodies were determined by
      commercially ELISA kits and the relation of infection with socio-demographic and
      risk factors such as age, education, occupation, cat ownership, soil contact and
      some other factors was studied. RESULTS: From 555 tested sera of pregnant women
      referred to Health Center in Gorgan, 39.8% had IgG antibodies against T. gondii
      and 3.4% were positive for IgM antibodies. A significant correlation was seen
      between T. gondii infection with age and soil contact. CONCLUSION: About 60% of
      pregnant women in Gorgan City are seronegative against T. gondii, so they should
      considered as at risk persons.

PMID- 25848384
TI  - Paleoparasitological Findings from Rodent Coprolites Dated At 500 CE Sassanid Era
      in Archeological Site of Chehrabad(Douzlakh), Salt Mine Northwestern Iran.
AB  - BACKGROUND: In this paper, paleoparasitological findings from rodent excrements
      obtained from Chehrabad Salt Mine archeological site located in northwest of Iran
      are demonstrated and discussed. METHODS: Chehrabad Salt Mine archeological site
      located in northwest of Iran, dated to the Achaemenid (mid 1(st) mill. BCE) and
      to Sassanid (3(rd) cent. - 7(th) cent. CE) period, is a unique study area to
      investigate parasites in the past millenniums in Iran. Rodent coprolites obtained
      from this archeological site were thoroughly analyzed for parasite eggs using TSP
      re-hydration technique. RESULTS: Specimen analyzed were attributed to juvenile
      and adult rats based on their apparent morphology comparing with the modern dried
      pellets of Muridea family. Helminth eggs retrieved from two positive pellets were
      identified as Trichosomoides crassicauda, yphacia sp. and Trichuris sp.
      CONCLUSION: The present paper discusses the first paleoparasitological findings
      of rodent gastrointestinal helminthes in Iran along with possible favorite items
      to rats in ancient Chehrabad Salt Mine.

PMID- 25848385
TI  - Acanthamoeba species in Swimming Pools of Cairo, Egypt.
AB  - BACKGROUND: The free-living amoebae Acanthamoeba spp. have been recognized as
      etiologic agents of amoebic encephalitis, keratitis, otitis, lung lesions and
      other skin infections mainly in immuno-compromised individuals. The purpose of
      this study is to detect the presence of Acanthamoeba in swimming pools in Egypt
      using a polymerase chain reaction (PCR) method. METHODS: Water samples were
      collected from 10 different swimming pools in Cairo, Egypt. Samples were cultured
      on non-nutrient agar for the detection of Acanthamoeba isolates that were
      confirmed by PCR amplification using genus specific primers. The molecularly
      confirmed Acanthamoeba isolates were morphologically identified to the species
      level. RESULTS: Members of genus Acanthamoeba were detected in 49.2% of the
      examined swimming-pool water samples. Morphologically, six Acanthamoeba species
      were isolated from the examined swimming pool water namely A. polyphaga,
      A.castellanii, A. rhysodes, A. mauritaniensis, A. royreba and A. triangularis.
      All the identified species of Acanthamoeba were molecularly confirmed to be
      related to the genus Acanthamoeba. CONCLUSION: The isolated species of
      Acanthamoeba could provoke variable degrees of infections to the swimmers. The
      culture method is cheaper and easier than PCR techniques that are faster for the
      detection of free-living amoebae.

PMID- 25848386
TI  - Triclabendazole (Anthelmintic Drug) Effects on the Excretory- Secretory Proteome
      of Fasciola hepatica in Two Dimension Electrophoresis Gel.
AB  - BACKGROUND: The aim of this study was to evaluate the protein spots of excretory 
      secretory products of Fasciola hepatica using two dimension electrophoresis
      method in the presence and absence of triclabendazole drug which can be
      considered to detect the target protein of the drug. METHODS: F. hepatica
      parasites were collected from infected cattle livers, divided in two groups and
      cultivated in RPMI 1640 medium. First group was treated with triclabendazole
      (TCBZ) and second group considered as control. The excretory-secretory (ES)
      products of each group were separated and total protein determined by Bradford
      method. To provide proteome spots, the ES proteins were precipitated and two
      dimension electrophoresis (2-DE) gel prepared. Protein amounts of two groups were
      compared using the statistical t-test and protein spots from 2-DE in test and
      control groups were also statistically analyzed. The protein spots of gels were
      identified by using protein database. RESULTS: The t-test showed a significant
      increase of total proteins in treated group (P<0.5). The protein spots count in
      the control group was less than test group however statistically not significant
      (p>0.05). Cathepsin L- protein (MW 36.7 pH 5.34), 14-3-3 epsilon 2 isoform (MW
      28.2 pH 5.36), Cathepsin L1D (MW 36.5 pH 5.8) and Cathepsin L1D (MW 36.6 pH 6.26)
      were identified in test group. CONCLUSION: It seems that, these results can be
      considered to determine the proteins which the drug acts as a target on them.

PMID- 25848387
TI  - Identification and Characterization of a Differentially Expressed Gene (07E12) in
      the Infective Larvae of the Parasitic Nematode Ascaris suum.
AB  - BACKGROUND: Parasitic nematodes cause animal and human diseases of major socio
      economic importance worldwide. The suppression of parasite development at
      particular developmental stages could provide an alternative approach for
      nematode control. In this study, Ascaris suum was used as a model system in the
      study of the differentially expressed genes in the infective L3 stage. METHODS:
      The gene (07E12) was screened and identified from the subtractive cDNA library
      for the infective larvae of Ascaris suum using real-time quantitative PCR. Then,
      the full-length cDNA of 07E12 was characterized by 3' and 5' rapid amplification
      of cDNA ends (RACE). The characteristics of the gene were further analyzed using
      bioinformatic analyses. RESULTS: The results showed that the gene 07E12 was
      differentially expressed in the third-stage larvae of A. suum and its expression
      level in the infective larvae was much higher than in other stages. It was shown
      that the gene 07E12 had 99% identity with the corresponding sequences of the A.
      suum whole genome shotgun sequence containing the homologous sequences with
      conserved sequences of Neuropeptide-Like Protein family member. Likewise, by
      performing BLASTN and BLASTP searches in the GenBankTM, it was shown that this
      gene had 99 % identity with A. suum cre-nlp-2 protein. CONCLUSION: This gene
      07E12 which is differentially expressed in the third-stage larvae of A. suum may
      encode a neuropeptide-like protein family member, a very important molecule in
      the process of infecting a host.

PMID- 25848388
TI  - Improved serodiagnosis of hydatid cyst disease using gold nanoparticle labeled
      antigen B in naturally infected sheep.
AB  - BACKGROUND: Cystic echinococcosis caused by the metacestode of Echinococcus
      granulosus is a major problem in both humans and domestic animals health.
      Therefore, a standardized and approachable diagnostic tool (rapid tests) for the
      serodiagnosis of cystic echinococcosis (CE) is still needed. METHODS: In the
      present work, antigen B labeled with gold nanoparticles was used to detect
      antibodies against hydatid cyst disease. The prepared antigen B was analyzed by
      SDS-PAGE. Tetra chloroauric acid (HAuCl4) was used to produce colloidal gold and
      antigen B labeled by gold nanoparticles, then it was tested by using rabbits
      antisera and sera from naturally infected sheep. The labeled antigen B was
      evaluated using Dot-immunogold staining (Dot-IGS) method. RESULTS:
      Electrophoretic pattern of hydatid cyst fluid showed the quality of bands in the
      condensed fluid is better than crude fluid. SDS-PAGE analysis cyst fluid and
      antigen B revealed three specific protein bands that were detected at molecular
      weights of 24, 30 and 40 kDa that all are the subunits of antigen B. Evaluation
      of antigen B labeled by gold nanoparticles by using Dot-IGS technique showed 1/1
      and 1/50 dilutions in comparison with another has the best immunoreaction. In
      this method, nanoparticles produced a typical purple color, when they binded to
      the strip at the site of immunoreaction. CONCLUSION: Therefore, using gold
      nanoparticles is a good candidate for detection of helminthiasis, also as
      selective tools of early detection, simple and cost-effective, regardless of
      specific skills and equipment with optimal durability.

PMID- 25848389
TI  - Cryptosporidium infection in patients with gastroenteritis in sari, iran.
AB  - BACKGROUND: Cryptosporidiosis is a common coccidian parasite infection in
      patients with diarrhea that has worldwide distribution especially in developed
      countries. Therefore, the aim of this study was to determine the occurrence of
      Cryptosporidium infection in patients with gastroenteritis admitted to hospitals
      of Mazandaran University of Medical Sciences by parasitological and molecular
      methods in Sari, Iran. METHODS: Stool samples were collected from 348 patients
      with gastroenteritis admitted to the hospitals of Medical University in the Sari
      and Ghaemshahr cities in Mazandaran Province, Northern Iran in 2010-2011. Oocysts
      of Cryptosporidium identified using Formalin-Ether concentration method and
      stained by Aacid-fast staining (AFS) and Auramine phenol fluorescence (APF).
      Genomic DAN extracted from microscopically positive samples and nested PCR -RFLP
      by using SSU rRNA that identifies of the species of cryptosporidium. RESULTS: In
      348 patients with gastroenteritis, the most clinical symptoms were diarrhea,
      nausea, vomiting, dehydration, fever and weight loss. 2.3% (8 cases) of diarrheal
      samples tested by both microscopy and molecular methods were positive for the
      presence of cryptosporidium. Nested PCR products yielded unique bands of 846 bp,
      correspond to cryptosporidium. Species diagnosis carried out by digesting the
      secondary PCR product with SspI restriction enzyme, which noted 3 clearly bands
      of 449, 254, and 108 bp correspond to Cryptosporidium spp. CONCLUSION: The
      results of present study on Cryptosporidium spp. in this area can make a
      background data for control programs and further molecular analyses. Thus,
      further work needs to determine the origin of Cryptosporidium species in this
      area.

PMID- 25848390
TI  - Hydatid Cyst Surgeries in Patients Referred to Hospitals in East Azerbaijan
      Province during 2009-2011.
AB  - BACKGROUND: Hydatidosis, as the most important zoonotic parasitic disease in
      Iran, has posed many health and economic losses. This study was conducted to
      investigate the demographic characteristics of hydatid cyst surgeries in
      hospitals of East Azerbaijan Province, Northwest of Iran. METHODS: Demographic
      characteristics of all patients with hydatid cyst surgery in hospitals of the
      province, during 2009-2011 were gathered including age, gender, occupation,
      number and location of the cyst, clinical symptoms, place of residence and
      history of contact with dog. They were extracted from reports of health center
      and were analyzed using STATA 11 software. RESULTS: Out of 52 hydatid cyst
      surgeries, 27 cases were females. Mean age of patients was 38.3 yr. Liver was
      reported as the most involved organ. The most clinical symptoms were abdominal
      and liver pain. Housewives comprised the most victims of the disease. Forty seven
      percent of patients had one cyst and 59% had the history of contact with dog. The
      majority of the patients were living in rural areas. CONCLUSION: Due to the high
      costs of diagnosis and treatment of hydatidosis, collecting data on the
      prevalence and transmission of the disease as well as on vulnerable groups seems
      to be essential as the first step in controlling and preventing the disease.

PMID- 25848391
TI  - Leishmaniasis in Turkey: Determination of Leishmania Species by Matrix-Assisted
      Laser Desorption Ionization Time-Of-Flight Mass Spectrometry (MALDI-TOF MS).
AB  - BACKGROUND: Cutaneous leishmaniasis (CL) is endemic in Southeastern Anatolia,
      mainly in Sanliurfa and Hatay provinces, and the causative agents are mostly
      Leishmania tropica and less frequently L. infantum. Here, we report the first
      MALDI-TOF analyses of Leishmania promastigotes obtained from the cultures of two
      CL cases from Osmaniye and Hatay provinces who were initially diagnosed by
      microscopy, culture and identified as L. infantum with Real-Time PCR (RT-PCR).
      METHODS: Samples obtained from the skin lesions of patients were initially
      stained with Giemsa and cultivated in NNN medium. Examination of the smears and
      cultures revealed Leishmania amastigotes and promastigotes, respectively. The
      promastigotes (MHOM/TR/2012/CBU15 and MHOM/TR/2012/MK05) obtained from the
      cultures of both patients were used for RT-PCR targeting the ITS-1 region in the
      SSU of rRNA. The reference strains of four Leishmania species (L. infantum, L.
      donovani, L. tropica and L. major) were initially assessed with MALDI-TOF and
      their data were added to MALDI-TOF Biotyper Library. RESULTS: Both RT-PCR and
      MALDI-TOF analyses indicated that the causative agent in both patient samples was
      L. infantum. CONCLUSION: Despite disadvantages such as requirement of culture
      fluid with nothing but promastigotes and high cost, MALDI-TOF analysis may be a
      fast, sensitive and specific diagnostic tool in especially large-scale research
      studies, where the cost declines, relatively.

PMID- 25848392
TI  - An epidemiological survey of setaria in the abdominal cavities of Iranian sistani
      and brahman cattle in the southeastern of iran.
AB  - BACKGROUND: In this experiment, abdominal cavity of 518 Iranian Sistani cattle
      and 498 Brahman cattle were inspected for the presence of Setaria spp. from April
      2012 - May 2013. METHODS: The species were determined by microscopic examination
      of the morphological characteristics of the anterior and posterior parts of the
      parasites and authentic guidelines. RESULTS: The overall prevalence of Setaria
      spp. was 28.6% and 36.5%, respectively and this difference was significant
      (P<0.05). Out of 148 Sistani cattle which were infected with Setaria, 51(34.4%)
      were infected with S. digitata, 31 (20.9%) were infected with S.
      labiatopapillosa, 65 (43.9%) showed mixed infection of S. digitata and S.
      labiatopapillosa and one case (0.6%) was infected with mixed infection of S.
      labiatopapillosa, S. digitata and S. marshalli. These values were 87 (47.8%), 27
      (14.8%), 67 (36.8%) and 1 (0.5%) for 182 infected Brahaman cows, respectively.
      The proportion of infected cattle in spring and summer was greater than cooler
      season (autumn and winter) significantly (P<0.001). The prevalence of infection
      with Setaria in 2-3 years old Sistatni cattle (42.2 %) was greater than other age
      categories (P<0.05). Furthermore, the infection rate between males (25.5%) and
      females (37.3%) Iranian Sistani cattle showed significant difference (P =0.009).
      CONCLUSION: It is important to point out the presence of cerebrospinal
      setariosis, namely in sheep, goats and horses in the investigated area.

PMID- 25848393
TI  - Isolation and identification of naegleria species from environmental water in
      changchun, northeastern china.
AB  - BACKGROUND: Naegleria is a free-living amoeba, and pathogenic Naegleria may pose
      a health risk to people exposed to recreational water. Our objective in this
      study was to determine if there are pathogenic amoebae in environmental water
      samples from Changchun, Northeastern China. METHODS: During July to September
      2012, a total of 70 water samples were collected from Changchun, Northeastern
      China, and Naegleria was enriched by in vitro culture and detected by PCR using
      Naegleria genus-specific primers. Resulting PCR products were sequenced and
      phylogenetically analyzed to identify Naegleria species. RESULTS: Naegleria was
      detected in 65 (92.9%) of 70 water samples. DNA sequence and phylogenetic
      analyses based on the internal transcribed spacer (ITS) rDNA sequences revealed
      four Naegleria species, including N. pagei (n = 24) and N. Australiensis (n =
      18), N. clarki (n = 13) and N. gruberi (n = 10), in which N. australiensis is
      pathogenic to mice. But the pathogenic species N. fowleri was not detected.
      CONCLUSION: This is the first report on Naegleria species in Northeastern China,
      showing that almost all environmental water samples were contaminated with
      Naegleria, including N. pagei, N. Australiensis, N. clarki and N. gruberi, which
      should be considered a potential public health threat.

PMID- 25848394
TI  - Integrating Morphology, Breeding Ground and Mitochondrial COI Gene Analysis for
      Species Identification of Bellamya lithophaga (Gastropoda: Viviparidae) in China.
AB  - BACKGROUND: Angiostrongylus cantonensis is a zoonotic public health concern that
      causes human severe eosinophilic meningitis in Southeast Asia and China. As a
      medically important intermediate host of A. cantonensis, Bellamya lithophaga
      (Gastropoda: Viviparidae) is often confused with other morphologically similar
      sibling species of genus Bellamya, such as B. aeruginosa and B. purificata in the
      past. Hence, the aim of the present study was to investigate evidences to
      discriminate these equivocal Bellamya species. METHODS: This study was carried
      out by getting Bellamya snail samples from Fujian Province in the South-East of
      China. The snail morphological features, breeding grounds and phylogenetic
      relationship according to mitochondrial cytochrome c oxidase subunit I (COI) gene
      marker were analyzed. RESULTS: Based on external morphology, radular shape and
      cusp formula, as well as major breeding environment, B. lithophaga could be
      distinguished from B. aeruginosa, B. purificata. The phylogenetic tree also
      unconfirmed that B. lithophaga belongs to a different genetic clade from other
      morphologically similar species. CONCLUSION: Our findings demonstrate the
      significant differences in B. lithophaga and other sibling species, which
      supports the traditional species delimitation in the genus Bellamya.

PMID- 25848395
TI  - A Histopathology Study of Caspian Seal (Pusa caspica) (Phocidae, Mammalia) Liver
      Infected with Trematode, Pseudamphistomum truncatum (Rudolphi, 1819)
      (Opisthorchidae, Trematoda).
AB  - BACKGROUND: Main objective of this study was to investigate the invasive activity
      of the liver fluke, Pseudamphistomom truncatum against the Caspian seal (Pusa
      caspica) and was exemplified at the gross, light microscopy (LM) and electron
      microscopy (EM) levels. METHODS: The study was done on a freshly dead Caspian
      Seal in the southern coast of Caspian Sea. The checked Caspian seal probably
      being died of canine distemper virus and was found host to numerous parasites of
      four helminth species. RESULTS: P. truncatum caused edematous foci on the surface
      of the liver with prominent fluid accumulation. Sections of the liver viewed with
      LM had multiple necrotic areas with extensive hemorrhaging and disorganized
      hepatic lobules. Granulocytes and invasion of connective tissue were prominent.
      Whole worms were visible with invasive pathways through the host tissue. Damage
      to both hepatic ducts and blood vessels were prominent. At the EM level,
      organelles within the impacted hepatocytes were disorganized as exemplified by
      the cristae of the mitochondria and the endoplasmic reticulum. Parasite eggs were
      scattered throughout the tissue. CONCLUSION: It was shown that this trematode can
      be very pathogenic to Caspian Seal and as this only mammal of Caspian Sea is an
      endangered species; this needs more investigation toward control or possible
      treatment of this helminth.

PMID- 25848396
TI  - Epidemiological study of gastrointestinal helminthes of canids in chaharmahal and
      bakhtiari province of iran.
AB  - BACKGROUND: The present study was carried out to describe the epidemiological
      aspects of gastrointestinal helminthic infections of canids in Chaharmahal and
      Bakhtiari Province, the central western part of Iran. METHODS: Forty nine canid
      species including, dogs, jackals, foxes and wolves were included in this study.
      The contents of their alimentary canal were inspected in order to isolate and
      identify the parasitic helminthes of this system. To identify the worms, the
      Soulsbey and Anderson identification key and light microscopy were used. RESULTS:
      Based on necropsy findings, 35 (71.4%) of examined animals were infected with at
      least one helminth. The prevalence of identified worms was as follows:
      Mesocestoides lineatus (55.1%), Joyeuxiella echinorinchoides (26.5%), Taenia
      hydatigena (12.2%), T. multiceps (8.2%), T. ovis (2%), Dipylidium caninum (2%)
      and Spirura spp. (2%). No significant difference was noticed between the sampling
      areas, age and helminth infection. Only a significant difference was observed for
      prevalence of T. multiceps in wolf (25%), dog (21.4%), jackal and fox (0%),
      respectively (P < 0.05). CONCLUSION: The canids in Chaharmahal and Bakhtiari
      harbor several parasites that some kind of them have zoonotic importance and may
      pose a threat to community health specially in rural areas.

PMID- 25848397
TI  - Human Linguatulosis Caused by Linguatula serrata in the City of Kerman, South
      eastern Iran- Case Report.
AB  - Human linguatulosis poses an important medical and veterinary concern in endemic
      countries. Animals, as reservoir host, play a major role in transmission of
      infestation and epidemiology of the disease. This study reports a case of human
      linguatulosis caused by Linguatula serrata in the city of Kerman, South-eastern
      Iran. A woman suffering from upper respiratory symptoms is presented. The patient
      consumed raw liver of sheep who was admitted to the Afzalipour University
      Hospital in Kerman for the symptoms of upper respiratory tract. In microscopic
      examination of the nasopharyngeal discharge, L. serrata was detected. This report
      has future medical implication in precise diagnosis of L. serrata in patients
      with complaints of nasopharyngeal symptoms. 

PMID- 25848398
TI  - First Molecular Identification of Sarcocystis ovicanis (Protozoa, Apicomplexa) in
      the Brain of Sheep in Iran.
AB  - BACKGROUND: The objective of the present study was to survey the presence of
      Sarcocystis in sheep's brain in North Khorasan Province. METHODS: In general, 80
      samples of sheep's brain were collected from slaughtered sheep in slaughterhouses
      of North Khorasan Province. Tissue digestion method was used for observing
      bradyzoites in tissues. Histopathological processing tracing Sarcocystis and
      ensuing structural change in the brain tissue were conducted. PCR analysis was
      conducted on all the brain samples. Sequencing was done for one PCR product.
      Genotype was identified by Blast search and homology analysis. RESULT:
      Sarcocystis spp. was found in one of the brain samples (1.25%) using tissue
      digestion method. The presence of bradyzoite was also confirmed in the prepared
      histopathological sections. PCR analysis was positive in one of samples.
      Genotyping of one sample proved that Sarcocystis species was Sarcocystis ovicanis
      and the nucleotide sequence of this parasite was deposited in the GenBank
      database under accession number No.KF489431. CONCLUSION: Sarcocystis ovicanis can
      involve brain tissue of sheep and consequently causes clinical symptoms.

PMID- 25848399
TI  - Mouse models of mastitis - how physiological are they?
AB  - Lactation mastitis is a common, but poorly understood, inflammatory breast
      disease that is a significant health burden. A better understanding of the
      aetiology of mastitis is urgently required, and will assist in the development of
      improved prevention and treatment strategies in both human and animal species.
      Studies in mice have the potential to greatly assist in identifying new drug
      candidates for clinical trials, and in developing a better understanding of the
      disease. Mouse models of mastitis involve administration of a mastitis-inducing
      agent to the mammary gland usually during lactation to examine the host immune
      response, and progression through to resolution of the disease. There are
      important variations in the protocols of these mouse models that critically
      affect the conclusions that can be drawn from the research. Some protocols
      involve weaning of offspring at the time of mastitis induction, and there are
      variations in the mastitis-inducing agent and its carrier. Induction of mammary
      gland involution through weaning of offspring limits the capacity to study the
      disease in the context of a lactating mammary gland. Administration of live
      bacteria in an aqueous carrier can cause sepsis, restricting the physiological
      relevance of the model. Mouse model research should employ appropriately designed
      controls and closely monitor the health of the mice. In this commentary, we
      discuss the advantages and study design limitations of each mouse model, and
      highlight the potential for further development of physiologically relevant mouse
      models of mastitis. 

PMID- 25848400
TI  - The relationship of weight change trajectory with medial temporal lobe atrophy in
      patients with mild Alzheimer's disease: results from a cohort study.
AB  - INTRODUCTION: Weight loss has been described in 20% to 45% of patients with
      Alzheimer's disease (AD) and has been associated with adverse outcomes. Various
      mechanisms for weight loss in AD patients have been proposed, though none has
      been proven. This study aimed to elucidate a mechanism of weight loss in AD
      patients by examining the hypothesis that weight loss is associated with medial
      temporal lobe atrophy (MTA). METHODS: Patients from the Frisian Alzheimer's
      disease cohort study (a retrospective, longitudinal study of 576 community
      dwelling AD patients) were included when a brain MRI was performed on which MTA
      could be assessed. To investigate the hypothesis that weight loss is associated
      with MTA, we investigated whether the trajectory of body weight change depends on
      the severity of MTA at the time of diagnosis (that is baseline). We hypothesized
      that patients with more severe MTA at baseline would have a lower body weight at
      baseline and a faster decrease in body weight during the course of the disease.
      The generalized linear mixed model (GLMM) was used to determine the relationship
      of weight change trajectory with MTA severity. RESULTS: In total, 214 patients
      (median age 79 years, median MMSE 23, mean weight 73.9 kg) were included.
      Patients with moderate, severe or very severe MTA at baseline weighed 3.2 to 6.8
      kg more than patients with no or mild MTA. During the 3.5 years, patients gained
      on average 1.7 kg in body weight, irrespective of the severity of their MTA at
      baseline. CONCLUSIONS: We found no evidence that MTA is associated with weight
      loss in AD patients. Moreover, contrary to what was expected, AD patients did not
      lose but gained weight during follow-up.

PMID- 25848402
TI  - Synergy of drug combinations in treating multidrug-resistant Pseudomonas
      aeruginosa.
AB  - BACKGROUND: With the emergence of metallo-betalactamases (MBL) in Pseudomonas
      aeruginosa (P. aeruginosa), the value of carbapenem, the drug of last resort, is
      being severely compromised. Curtailing the use of carbapenems becomes paramount
      if resistance is to be reined in. AIMS: To study the role of synergy between
      combinations of drugs as an alternative treatment choice for P. aeruginosa.
      Synergy was studied between combinations of levofloxacin with piperacillin
      tazobactam and levofloxacin with cefoperazone-sulbactam by time-kill and
      chequerboard techniques. METHODS: P. aeruginosa were tested for antibiotic
      susceptibility by the disc diffusion assay (260 isolates) and E-test (60
      isolates). Synergy testing by chequerboard and time-kill assays was performed
      with combinations of piperacillin-tazobactam with levofloxacin (11 isolates) and
      cefoperazone-sulbactam with levofloxacin (10 isolates). RESULTS: Nearly all
      isolates were susceptible to piperacillin-tazobactam (96.1 per cent), followed by
      piperacillin (78.5 per cent). Seventy-one isolates (27.3 per cent) were found to
      be multidrug resistant and 19.6 per cent were ESBL producers. MIC50 of amikacin
      was 32MUg/ml and MIC90 was 64MUg/ml. MIC50 and MIC90 of cefoperazone-sulbactam
      was 32MUg/ml and 64MUg/ml, and for levofloxacin it was 10MUg/ml and 240MUg/ml,
      respectively. Piperacillin-tazobactam had MIC50 and MIC90 of 5MUg/ml and
      10MUg/ml, respectively. Synergy was noted in 72.7 per cent isolates for
      levofloxacin and piperacillin-tazobactam combination, the remaining 27.3 per cent
      isolates showed addition by both chequerboard and time-kill assay. For
      levofloxacin and cefoperazone-sulbactam, only 30 per cent isolates had synergy,
      40 per cent showed addition, 20 per cent indifference, and 10 per cent were
      antagonistic by the chequerboard method. CONCLUSION: The combination of
      levofloxacin and piperacillin-tazobactam is a good choice for treatment of such
      strains.

PMID- 25848401
TI  - HIV effects on age-associated neurocognitive dysfunction: premature cognitive
      aging or neurodegenerative disease?
AB  - Marked improvements in survival and health outcome for people infected with HIV
      have occurred since the advent of combination antiretroviral therapy over a
      decade ago. Yet HIV-associated neurocognitive disorders continue to occur with an
      alarming prevalence. This may reflect the fact that infected people are now
      living longer with chronic infection. There is mounting evidence that HIV
      exacerbates age-associated cognitive decline. Many middle-aged HIV-infected
      people are experiencing cognitive decline similar that to that found among much
      older adults. An increased prevalence of vascular and metabolic comorbidities has
      also been observed and is greatest among older adults with HIV. Premature age
      associated neurocognitive decline appears to be related to structural and
      functional brain changes on neuroimaging, and of particular concern is the fact
      that pathology indicative of neurodegenerative disease has been shown to occur in
      the brains of HIV-infected people. Yet notable differences also exist between the
      clinical presentation and brain disturbances occurring with HIV and those
      occurring in neurodegenerative conditions such as Alzheimer's disease. HIV
      interacts with the aging brain to affect neurological structure and function.
      However, whether this interaction directly affects neurodegenerative processes,
      accelerates normal cognitive aging, or contributes to a worsening of other
      comorbidities that affect the brain in older adults remains an open question.
      Evidence for and against each of these possibilities is reviewed. 

PMID- 25848403
TI  - Percutaneous aspiration versus catheter drainage of liver abscess: A
      retrospective review.
AB  - BACKGROUND: A review of the effectiveness and outcomes in liver abscess drainage
      performed by different operators using percutaneous aspiration (PA) and catheter
      drainage (PCD), respectively, from 2008-2013 at Sir Charles Gairdner Hospital, a
      tertiary hospital in Australia. METHODS: Forty-two patients (29 males and 13
      females; aged between 28-93 years; median age of 67 years) with liver abscesses
      underwent either ultrasound or CT-guided PA (n=22) and PCD (n=20) in conjunction
      with appropriate antimicrobial therapy. A median of 18 Gauge needle and 10 French
      catheters were utilised. RESULTS: Nineteen (86.4 per cent) PA cases and 12 (60
      per cent) PCD cases were successfully drained on a single attempt (p=0.08). More
      male patients (69 per cent) than females (31 per cent) were observed. Portal
      sepsis (42.9 per cent) was the most common cause identified. Fever (47.6 per
      cent) was the most frequent clinical presentation on admission. Thirty-two
      patients (76.2 per cent) had solitary abscesses with a right lobe (59.5 per cent)
      predilection. CRP was significantly raised. The PCD group observed a
      significantly larger abscess size (p=0.01). Klebsiella pneumoniae was the most
      common organism isolated in both pus (33.3 per cent) and blood cultures (11.9 per
      cent). Five procedure-related complications were noted, all in the PCD group.
      Thirty-day mortality was 2.4 per cent. No difference was observed in clinical and
      treatment outcomes in both groups. CONCLUSION: The null hypothesis that both PA
      and PCD are equally effective in the drainage of liver abscess cannot be
      rejected. Apart from PA being simpler and safer to perform, the higher incidence
      of indwelling catheter-associated complications suggests that a trial of PA
      should always be attempted first.

PMID- 25848404
TI  - Selective myelosuppression following yellow phosphorus ingestion.
AB  - Toxicity from accidental and intentional ingestion of yellow phosphorus,
      ubiquitously present in fireworks and rodenticides, has recently become more
      frequent. Gastrointestinal, renal, neurologic, and cardiovascular manifestations
      are common, with mortality of 23 per cent to 73 per cent. Reports of
      haematological abnormalities are rare. We report only the second case of severe
      neutropenia secondary to selective myelosuppression in a 14-year-old girl
      following intentional ingestion of yellow phosphorus. Leucocyte counts recovered
      spontaneously without further complications. Our case indicates that, besides
      hepatic and renal function monitoring, physicians should meticulously monitor
      blood counts in such cases for early detection of marrow suppression. Further
      studies are required to elucidate the complex mechanisms and significance of this
      unusual toxicity of yellow phosphorus. 

PMID- 25848405
TI  - A unique case of bilateral sciatic nerve variation within the gluteal compartment
      and associated clinical ramifications.
AB  - An abnormal course of a nerve either through or around a muscle may yield
      multiple or anomalous muscle innervation. Further, if nerves are inappropriately
      trapped within the confines of a muscle or irregular boundaries, variant
      emergence of a nerve could give rise to symptoms of an entrapment neuropathy.
      Upon routine dissection in the Department of Anatomy at the American University
      of Antigua College of Medicine, bilateral variants in the emergence of the
      sciatic nerve from the pelvis to the gluteal compartment were discovered in an
      elderly adult female cadaver. In the left gluteal compartment, the sciatic nerve
      had a high division where the peroneal division exited the pelvis superior to the
      piriformis muscle while the tibial division exited inferior to the piriformis. In
      the right gluteal compartment, the peroneal division was observed to have exited
      the pelvis between a split piriformis muscle before it joined the tibial division
      of the sciatic nerve. Knowledge of such variations in the course of the sciatic
      nerve may improve diagnosis and treatment of pathologies in this region. 

PMID- 25848406
TI  - Should Australia consider opt-out HIV testing?

PMID- 25848407
TI  - N-Cadherin-Mediated Signaling Regulates Cell Phenotype for Nucleus Pulposus Cells
      of the Intervertebral Disc.
AB  - Juvenile nucleus pulposus (NP) cells of the intervertebral disc (IVD) are large,
      vacuolated cells that form cell clusters with strong cell-cell interactions. With
      maturation and aging, NP cells lose their ability to form these cell clusters,
      with aging-associated changes in NP cell phenotype, morphology, and proteoglycan
      synthesis that may contribute to IVD degeneration. Therefore, it is important to
      understand the mechanisms governing juvenile NP cell cluster behavior towards the
      goal of revealing factors that can promote juvenile, healthy NP cell phenotypes.
      N-cadherin has been identified as a cell-cell adhesion marker that is present in
      juvenile NP cells, but disappears with age. The goal of this study was to reveal
      the importance of N-cadherin in regulating cell-cell interactions in juvenile NP
      cell cluster formation and test for a regulatory role in maintaining a juvenile
      NP phenotype in vitro. Juvenile porcine IVD cells, of notochordal origin, were
      promoted to form cell clusters in vitro, and analyzed for preservation of the
      juvenile NP phenotype. Additionally, cadherin-blocking experiments were performed
      to prevent cluster formation in order to study the importance of cluster
      formation in NP cell signaling. Findings reveal N-cadherin-mediated cell-cell
      contacts promote cell clustering behavior and regulate NP cell matrix production
      and preservation of NP-specific markers. Inhibition of N-cadherin-mediated
      contacts resulted in loss of all features of the juvenile NP cell. These results
      establish a regulatory role for N-cadherin in juvenile NP cells, and suggest that
      preservation of the N-cadherin mediated cell-cell contact is important for
      preserving juvenile NP cell phenotype and morphology.

PMID- 25848408
TI  - Testing a Moderated Mediation Model of Mindfulness, Psychosocial Stress, and
      Alcohol Use among African American Smokers.
AB  - Mindfulness-based strategies have received empirical support for improving coping
      with stress and reducing alcohol use. The present study presents a moderated
      mediation model to explain how mindfulness might promote healthier drinking
      patterns. This model posits that mindfulness reduces perceived stress, leading to
      less alcohol use, and also weakens the linkage between stress and alcohol use.
      African American smokers (N = 399, 51% female, Mage = 42) completed measures of
      dispositional mindfulness, perceived stress, quantity of alcohol use, frequency
      of binge drinking, and alcohol use disorder symptoms. Participants with higher
      levels of dispositional mindfulness reported less psychosocial stress and lower
      alcohol use on all measures. Furthermore, mindfulness moderated the relationship
      between perceived stress and quantity of alcohol consumption. Specifically,
      higher perceived stress was associated with increased alcohol use among
      participants low, but not high, in mindfulness. Mindfulness may be one strategy
      to reduce perceived stress and associated alcohol use among African American
      smokers.

PMID- 25848410
TI  - Legal and regulatory considerations associated with use of patient-generated
      health data from social media and mobile health (mHealth) devices.
AB  - Patient-generated health data are coming into broader use across the health care
      spectrum and hold great promise as a means to improve care and health outcomes.
      At the same time, rapid evolution in the social media and mobile health (mHealth)
      market has promoted an environment in which creation and transmission of personal
      health information is easy, quick, and appealing to patients. However, adoption
      of social media and mHealth by providers is hampered by legal and regulatory
      concerns with regard to data ownership and data use. This article defines common
      forms of patient-generated health data (PGHD) and describes how PGHD is used in
      clinical settings. It explores issues related to protection of personal health
      information, including that of children and adolescents, data security, and other
      potential barriers such as physician licensure. It also discusses regulatory and
      legal considerations providers and patients should consider before using social
      media and mobile health apps. 

PMID- 25848409
TI  - Leveraging electronic tablets for general pediatric care: a pilot study.
AB  - BACKGROUND: We have previously shown that a scan-able paper based interface
      linked to a computerized clinical decision support system (CDSS) can effectively
      screen patients in pediatric waiting rooms and support the physician using
      evidence based care guidelines at the time of clinical encounter. However, the
      use of scan-able paper based interface has many inherent limitations including
      lacking real time communication with the CDSS and being prone to human and system
      errors. An electronic tablet based user interface can not only overcome these
      limitations, but may also support advanced functionality for clinical and
      research use. However, use of such devices for pediatric care is not well studied
      in clinical settings. OBJECTIVE: In this pilot study, we enhance our pediatric
      CDSS with an electronic tablet based user interface and evaluate it for usability
      as well as for changes in patient questionnaire completion rates. METHODS: Child
      Health Improvement through Computers Leveraging Electronic Tablets or CHICLET is
      an electronic tablet based user interface. It is developed to augment the
      existing scan-able paper interface to our CDSS. For the purposes of this study,
      we deployed CHICLET in one outpatient pediatric clinic. Usability factors for
      CHICLET were evaluated via caregiver and staff surveys. RESULTS: When compared to
      the scan-able paper based interface, we observed an 18% increase or 30% relative
      increase in question completion rates using CHICLET. This difference was
      statistically significant. Caregivers and staff survey results were positive for
      using CHICLET in clinical environment. CONCLUSIONS: Electronic tablets are a
      viable interface for capturing patient self-report in pediatric waiting rooms. We
      further hypothesize that the use of electronic tablet based interfaces will drive
      advances in computerized clinical decision support and create opportunities for
      patient engagement.

PMID- 25848411
TI  - Emergency medicine resident physicians' perceptions of electronic documentation
      and workflow: a mixed methods study.
AB  - OBJECTIVE: To understand emergency department (ED) physicians' use of electronic
      documentation in order to identify usability and workflow considerations for the
      design of future ED information system (EDIS) physician documentation modules.
      METHODS: We invited emergency medicine resident physicians to participate in a
      mixed methods study using task analysis and qualitative interviews. Participants
      completed a simulated, standardized patient encounter in a medical simulation
      center while documenting in the test environment of a currently used EDIS. We
      recorded the time on task, type and sequence of tasks performed by the
      participants (including tasks performed in parallel). We then conducted semi
      structured interviews with each participant. We analyzed these qualitative data
      using the constant comparative method to generate themes. RESULTS: Eight resident
      physicians participated. The simulation session averaged 17 minutes and
      participants spent 11 minutes on average on tasks that included electronic
      documentation. Participants performed tasks in parallel, such as history taking
      and electronic documentation. Five of the 8 participants performed a similar
      workflow sequence during the first part of the session while the remaining three
      used different workflows. Three themes characterize electronic documentation: (1)
      physicians report that location and timing of documentation varies based on
      patient acuity and workload, (2) physicians report a need for features that
      support improved efficiency; and (3) physicians like viewing available patient
      data but struggle with integration of the EDIS with other information sources.
      CONCLUSION: We confirmed that physicians spend much of their time on
      documentation (65%) during an ED patient visit. Further, we found that resident
      physicians did not all use the same workflow and approach even when presented
      with an identical standardized patient scenario. Future EHR design should
      consider these varied workflows while trying to optimize efficiency, such as
      improving integration of clinical data. These findings should be tested
      quantitatively in a larger, representative study.

PMID- 25848412
TI  - Association between electronic health records and health care utilization.
AB  - BACKGROUND: The federal government is investing approximately $20 billion in
      electronic health records (EHRs), in part to address escalating health care
      costs. However, empirical evidence that provider use of EHRs decreases health
      care costs is limited. OBJECTIVE: To determine any association between EHRs and
      health care utilization. METHODS: We conducted a cohort study (2008-2009) in the
      Hudson Valley, a multi-payer, multiprovider community in New York State. We
      included 328 primary care physicians in predominantly small practices (median
      practice size four primary care physicians), who were caring for 223,772
      patients. Data from an independent practice association was used to determine
      adoption of EHRs. Claims data aggregated across five commercial health plans was
      used to characterize seven types of health care utilization: primary care visits,
      specialist visits, radiology tests, laboratory tests, emergency department
      visits, hospital admissions, and readmissions. We used negative binomial
      regression to determine associations between EHR adoption and each utilization
      outcome, adjusting for ten physician characteristics. RESULTS: Approximately half
      (48%) of the physicians were using paper records and half (52%) were using EHRs.
      For every 100 patients seen by physicians using EHRs, there were 14 fewer
      specialist visits (adjusted p < 0.01) and 9 fewer radiology tests (adjusted p =
      0.01). There were no significant differences in rates of primary care visits,
      laboratory tests, emergency department visits, hospitalizations or readmissions.
      CONCLUSIONS: Patients of primary care providers who used EHRs were less likely to
      have specialist visits and radiology tests than patients of primary care
      providers who did not use EHRs.

PMID- 25848413
TI  - CorRECTreatment: a web-based decision support tool for rectal cancer treatment
      that uses the analytic hierarchy process and decision tree.
AB  - BACKGROUND: The selection of appropriate rectal cancer treatment is a complex
      multi-criteria decision making process, in which clinical decision support
      systems might be used to assist and enrich physicians' decision making.
      OBJECTIVE: The objective of the study was to develop a web-based clinical
      decision support tool for physicians in the selection of potentially beneficial
      treatment options for patients with rectal cancer. METHODS: The updated decision
      model contained 8 and 10 criteria in the first and second steps respectively. The
      decision support model, developed in our previous study by combining the Analytic
      Hierarchy Process (AHP) method which determines the priority of criteria and
      decision tree that formed using these priorities, was updated and applied to 388
      patients data collected retrospectively. Later, a web-based decision support tool
      named corRECTreatment was developed. The compatibility of the treatment
      recommendations by the expert opinion and the decision support tool was examined
      for its consistency. Two surgeons were requested to recommend a treatment and an
      overall survival value for the treatment among 20 different cases that we
      selected and turned into a scenario among the most common and rare treatment
      options in the patient data set. RESULTS: In the AHP analyses of the criteria, it
      was found that the matrices, generated for both decision steps, were consistent
      (consistency ratio<0.1). Depending on the decisions of experts, the consistency
      value for the most frequent cases was found to be 80% for the first decision step
      and 100% for the second decision step. Similarly, for rare cases consistency was
      50% for the first decision step and 80% for the second decision step.
      CONCLUSIONS: The decision model and corRECTreatment, developed by applying these
      on real patient data, are expected to provide potential users with decision
      support in rectal cancer treatment processes and facilitate them in making
      projections about treatment options.

PMID- 25848414
TI  - The value of clinical teachers for EMR implementations and conversions.
AB  - Effective physician training is an essential aspect of EMR implementation.
      However, it can be challenging to find instructors who can present the material
      in a clinically relevant manner. The authors describe a unique physician-training
      program, utilizing medical students as course instructors. This approach resulted
      in high learner satisfaction rates and provided significant cost-savings compared
      to alternative options. 

PMID- 25848415
TI  - Successful physician training program for large scale EMR implementation.
AB  - End-user training is an essential element of electronic medical record (EMR)
      implementation and frequently suffers from minimal institutional investment. In
      addition, discussion of successful EMR training programs for physicians is
      limited in the literature. The authors describe a successful physician-training
      program at Stanford Children's Health as part of a large scale EMR
      implementation. Evaluations of classroom training, obtained at the conclusion of
      each class, revealed high physician satisfaction with the program. Free-text
      comments from learners focused on duration and timing of training, the learning
      environment, quality of the instructors, and specificity of training to their
      role or department. Based upon participant feedback and institutional experience,
      best practice recommendations, including physician engagement, curricular design,
      and assessment of proficiency and recognition, are suggested for future provider
      EMR training programs. The authors strongly recommend the creation of coursework
      to group providers by common workflow. 

PMID- 25848416
TI  - Data collection methods in health services research: hospital length of stay and
      discharge destination.
AB  - BACKGROUND: Hospital length of stay and discharge destination are important
      outcome measures in evaluating effectiveness and efficiency of health services.
      Although hospital administrative data are readily used as a data collection
      source in health services research, no research has assessed this data collection
      method against other commonly used methods. OBJECTIVE: Determine if
      administrative data from electronic patient management programs are an effective
      data collection method for key hospital outcome measures when compared with
      alternative hospital data collection methods. METHOD: Prospective observational
      study comparing the completeness of data capture and level of agreement between
      three data collection methods; manual data collection from ward-based sources,
      administrative data from an electronic patient management program (i.PM), and
      inpatient medical record review (gold standard) for hospital length of stay and
      discharge destination. RESULTS: Manual data collection from ward-based sources
      captured only 376 (69%) of the 542 inpatient episodes captured from the hospital
      administrative electronic patient management program. Administrative data from
      the electronic patient management program had the highest levels of agreement
      with inpatient medical record review for both length of stay (93.4%) and
      discharge destination (91%) data. CONCLUSION: This is the first paper to
      demonstrate differences between data collection methods for hospital length of
      stay and discharge destination. Administrative data from an electronic patient
      management program showed the highest level of completeness of capture and level
      of agreement with the gold standard of inpatient medical record review for both
      length of stay and discharge destination, and therefore may be an acceptable data
      collection method for these measures.

PMID- 25848417
TI  - A national survey of parent perspectives on use of patient portals for their
      children's health care.
AB  - OBJECTIVES: To assess parents' current utilization and future willingness to use
      patient portals to interact with their child's health care provider. METHODS: A
      cross-sectional survey of a nationally representative sample of US parents was
      conducted using an established online panel. Bivariate analyses assessed
      associations between current utilization and future willingness to use patient
      portals, parental concerns, and demographic variables. RESULTS: Among the 1,420
      parent respondents, 40% did not know whether their child's health practice offers
      the option of setting up a patient portal for their child. Of the 21% of parents
      who reported being offered the option of setting up a patient portal for their
      child, 59% had done so. Among parents who had the option but chose not to set up
      a patient portal for their child, lack of time and low perceived need were the
      main reasons cited. Current use and likelihood of future use was highest for
      viewing lab results and immunization records. The most common concern about
      patient portals was the security of the child portal system. CONCLUSIONS: Current
      use of patient portals by parents is low. Only about half of parents currently
      using or likely to use a portal perceive value in using portals for certain
      tasks, which suggests that providers will need to continue traditional
      communication mechanisms to reach their entire patient population.

PMID- 25848419
TI  - Electronic health records and patient safety: co-occurrence of early EHR
      implementation with patient safety practices in primary care settings.
AB  - BACKGROUND: The role of electronic health records (EHR) in enhancing patient
      safety, while substantiated in many studies, is still debated. OBJECTIVE: This
      paper examines early EHR adopters in primary care to understand the extent to
      which EHR implementation is associated with the workflows, policies and practices
      that promote patient safety, as compared to practices with paper records. Early
      adoption is defined as those who were using EHR prior to implementation of the
      Meaningful Use program. METHODS: We utilized the Physician Practice Patient
      Safety Assessment (PPPSA) to compare primary care practices with fully
      implemented EHR to those utilizing paper records. The PPPSA measures the extent
      of adoption of patient safety practices in the domains: medication management,
      handoffs and transition, personnel qualifications and competencies, practice
      management and culture, and patient communication. RESULTS: Data from 209 primary
      care practices responding between 2006-2010 were included in the analysis: 117
      practices used paper medical records and 92 used an EHR. Results showed that,
      within all domains, EHR settings showed significantly higher rates of having
      workflows, policies and practices that promote patient safety than paper record
      settings. While these results were expected in the area of medication management,
      EHR use was also associated with adoption of patient safety practices in areas in
      which the researchers had no a priori expectations of association. CONCLUSIONS:
      Sociotechnical models of EHR use point to complex interactions between technology
      and other aspects of the environment related to human resources, workflow,
      policy, culture, among others. This study identifies that among primary care
      practices in the national PPPSA database, having an EHR was strongly empirically
      associated with the workflow, policy, communication and cultural practices
      recommended for safe patient care in ambulatory settings.

PMID- 25848418
TI  - Use of computer decision support in an antimicrobial stewardship program (ASP).
AB  - OBJECTIVE: Document information needs, gaps within the current electronic
      applications and reports, and workflow interruptions requiring manual information
      searches that decreased the ability of our antimicrobial stewardship program
      (ASP) at Intermountain Healthcare (IH) to prospectively audit and provide
      feedback to clinicians to improve antimicrobial use. METHODS: A framework was
      used to provide access to patient information contained in the electronic medical
      record, the enterprise-wide data warehouse, the data-driven alert file and the
      enterprise-wide encounter file to generate alerts and reports via pagers, emails
      and through the Centers for Diseases and Control's National Healthcare
      Surveillance Network. RESULTS: Four new applications were developed and used by
      ASPs at Intermountain Medical Center (IMC) and Primary Children's Hospital (PCH)
      based on the design and input from the pharmacists and infectious diseases
      physicians and the new Center for Diseases Control and Prevention/National
      Healthcare Safety Network (NHSN) antibiotic utilization specifications. Data from
      IMC and PCH now show a general decrease in the use of drugs initially targeted by
      the ASP at both facilities. CONCLUSIONS: To be effective, ASPs need an enormous
      amount of "timely" information. Members of the ASP at IH report these new
      applications help them improve antibiotic use by allowing efficient, timely
      review and effective prioritization of patients receiving antimicrobials in order
      to optimize patient care.

PMID- 25848420
TI  - Implementation of an audio computer-assisted self-interview (ACASI) system in a
      general medicine clinic: patient response burden.
AB  - BACKGROUND: Routine implementation of instruments to capture patient-reported
      outcomes could guide clinical practice and facilitate health services research.
      Audio interviews facilitate self-interviews across literacy levels. OBJECTIVES:
      To evaluate time burden for patients, and factors associated with response times
      for an audio computer-assisted self interview (ACASI) system integrated into the
      clinical workflow. METHODS: We developed an ACASI system, integrated with a
      research data warehouse. Instruments for symptom burden, self-reported health,
      depression screening, tobacco use, and patient satisfaction were administered
      through touch-screen monitors in the general medicine clinic at the Cook County
      Health & Hospitals System during April 8, 2011-July 27, 2012. We performed a
      cross-sectional study to evaluate the mean time burden per item and for each
      module of instruments; we evaluated factors associated with longer response
      latency. RESULTS: Among 1,670 interviews, the mean per-question response time was
      18.4 [SD, 6.1] seconds. By multivariable analysis, age was most strongly
      associated with prolonged response time and increased per decade compared to < 50
      years as follows (additional seconds per question; 95% CI): 50-59 years (1.4; 0.7
      to 2.1 seconds); 60-69 (3.4; 2.6 to 4.1); 70-79 (5.1; 4.0 to 6.1); and 80-89
      (5.5; 4.1 to 7.0). Response times also were longer for Spanish language (3.9; 2.9
      to 4.9); no home computer use (3.3; 2.8 to 3.9); and, low mental self-reported
      health (0.6; 0.0 to 1.1). However, most interviews were completed within 10
      minutes. CONCLUSIONS: An ACASI software system can be included in a patient visit
      and adds minimal time burden. The burden was greatest for older patients,
      interviews in Spanish, and for those with less computer exposure. A patient's
      self-reported health had minimal impact on response times.

PMID- 25848422
TI  - Hospital closure and insights into patient dispersion: the closure of Saint
      Vincent's Catholic Medical Center in New York City.
AB  - BACKGROUND: Hospital closures are becoming increasingly common in the United
      States. Patients who received care at the closing hospitals must travel to
      different, often farther hospitals for care, and nearby remaining hospitals may
      have difficulty coping with a sudden influx of patients. OBJECTIVES: Our
      objectives are to analyze the dispersion patterns of patients from a closing
      hospital and to correlate that with distance from the closing hospital for three
      specific visit types: emergency, inpatient, and ambulatory. METHODS: In this
      study, we used data from a health information exchange to track patients from
      Saint Vincent's Medical Center, a hospital in New York City that closed in 2010,
      to determine where they received emergency, inpatient, and ambulatory care
      following the closure. RESULTS: We found that patients went to the next nearest
      hospital for their emergency and inpatient care, but ambulatory encounters did
      not correlate with distance. DISCUSSION: It is likely that patients followed
      their ambulatory providers as they transitioned to another hospital system.
      Additional work should be done to determine predictors of impact on nearby
      hospitals when another hospital in the community closes in order to better
      prepare for patient dispersion.

PMID- 25848421
TI  - Convergent evolution of health information management and health informatics: a
      perspective on the future of information professionals in health care.
AB  - Clearly defined boundaries are disappearing among the activities, sources, and
      uses of health care data and information managed by health information management
      (HIM) and health informatics (HI) professionals. Definitions of the professional
      domains and scopes of practice for HIM and HI are converging with the
      proliferation of information and communication technologies in health care
      settings. Convergence is changing both the roles that HIM and HI professionals
      serve in their organizations as well as the competencies necessary for training
      future professionals. Many of these changes suggest a blurring of roles and
      responsibilities with increasingly overlapping curricula, job descriptions, and
      research agendas. Blurred lines in a highly competitive market create confusion
      for students and employers. In this essay, we provide some perspective on the
      changing landscape and suggest a course for the future. First we review the
      evolving definitions of HIM and HI. We next compare the current domains and
      competencies, review the characteristics as well as the education and
      credentialing of both disciplines, and examine areas of convergence. Given the
      current state, we suggest a path forward to strengthen the contributions HIM and
      HI professionals and educators make to the evolving health care environment. 

PMID- 25848424
TI  - Erratum to: identifying consumer's needs of health information technology through
      an innovative participatory design approach among English- and Spanish-speaking
      urban older adults.

PMID- 25848423
TI  - Collaboration leads to enhanced curriculum.
AB  - BACKGROUND: In 2007, we initiated a health information management (HIM) track of
      our biomedical informatics graduate program, and subsequent ongoing program
      assessment revealed a confluence of topics and courses within HIM and clinical
      informatics (CI) tracks. We completed a thorough comparative analysis of
      competencies derived from AMIA, AHIMA, and CAHIIM. Coupled with the need to
      streamline course offerings, the process, described in this paper allowed new
      opportunities for faculty collaboration, resulted in the creation of a model
      assessment for best practice in courses, and led to new avenues of growth within
      the program. OBJECTIVE: The objective of the case study is to provide others in
      the informatics educational community with a model for analysis of curriculum in
      order to improve quality of student learning. METHODS: We describe a case study
      where an academic informatics program realigned its course offerings to better
      reflect the HIM of today, and prepare for challenges of the future. Visionary
      leadership, intra-departmental self-analysis and alignment of the curriculum
      through defined mapping process reduced overlap within the CI and HIM tracks.
      Teaching within courses was optimized through the work of core faculty
      collaboration. RESULTS: The analysis of curriculum resulted in reduction of
      overlap within course curriculum. This allowed for additional and new course
      content to be added to existing courses. CONCLUSIONS: Leadership fostered an
      environment where top-down as well as bottom-up collaborative assessment
      activities resulted in a model to consolidate learning and reduce unnecessary
      duplication within courses. A focus on curriculum integration, emphasis on course
      alignment and strategic consolidation of course content raised the quality of
      informatics education provided to students. Faculty synergy was an essential
      component of this redesign process. Continuous quality improvement strategy
      included an ongoing alignment of curriculum and competencies through a
      comparative analysis approach. Through these efforts, new innovation was
      possible.

PMID- 25848425
TI  - Cerebral lesions in patients undergoing coronary artery bypass grafting in
      relation to asymptomatic carotid and vertebral artery stenosis.
AB  - OBJECTIVES: Carotid artery stenosis (CAS) and vertebral artery stenosis (VAS) are
      associated with cerebral infarction after coronary artery bypass graft surgery
      (CABG). It remains unclear whether this association is causal. We investigated
      the associations between neurologically asymptomatic CAS and VAS and the
      occurrence of subclinical cerebral lesions after CABG verified by magnetic
      resonance imaging. METHODS: CABG patients were included and CAS and VAS were
      identified by magnetic resonance angiography. Cerebral magnetic resonance imaging
      was performed to identify new post-operative subclinical cerebral lesions. The
      associations between CAS/VAS post-operative cerebral lesions were investigated.
      RESULTS: Forty-six patients were included in the study. 13% had significant CAS
      and 11% had significant VAS. Thirty-five percent had new cerebral infarction
      postoperatively. We found a significant association between the presence of
      cerebral vessel stenosis and acute cerebral infarction (67% vs. 27%, p = 0.047).
      However none of the patients with stenosis had isolated cerebral lesions in the
      ipsilateral vascular territory. CONCLUSION: Asymptomatic CAS and VAS is common in
      CABG patients and is associated with an increased risk of postoperative cerebral
      infarction. Our study suggests that asymptomatic CAS and VAS primarily are risk
      markers rather than causal factors for cerebral infarction after CABG.

PMID- 25848426
TI  - Long-term results of combined aortoiliac and infrainguinal arterial
      reconstruction for the treatment of critical limb ischemia.
AB  - OBJECTIVE: This study was designed to investigate our long-term experience with
      combined iliac endovascular therapy (EVT) and infrainguinal bypass to treat
      critical limb ischemia (CLI) and compare outcomes to those of patients who
      underwent surgery for aortoiliac lesions. MATERIALS AND METHODS: From April 2000
      to June 2013, 57 patients (58 limbs) underwent an infrainguinal bypass combined
      with aortoiliac reconstruction to treat CLI. Eighteen limbs were treated by
      bypass alone and 8 limbs were treated by bypass with EVT for aortoiliac lesions
      (Bypass group). Thirty-two limbs were subjected to EVT alone for iliac lesions
      (EVT group). RESULTS: Preoperative limb ischemia was more severe in the EVT
      group. There were no significant differences in major procedure-related
      complications (chi(2) test, P = 0.853), systemic complications (P = 0.853), and
      mortality (P = 0.916) between the 2 groups. The limb salvage rates were 92% at 1,
      3, and 5 years in the Bypass group and 93% at 1, 3, and 5 years in the EVT group,
      with no significant difference observed between the groups (Kaplan-Meier, log
      rank test, P = 0.616). CONCLUSION: Infrainguinal surgical reconstruction combined
      with an iliac EVT is an acceptable strategy for managing patients with CLI.

PMID- 25848428
TI  - Aortic fenestration for type B chronic aortic dissection complicated with lower
      limb malperfusion induced by walking exercise.
AB  - We report a case of a 55-year-old male with type B-chronic aortic dissection.
      Patient presented with intermittent claudication due to limb malperfusion
      resulting from expansion of a patent false lumen during walking regardless of
      normal range ankle-brachial index (ABI) at rest. Preoperative stress vascular
      ultrasonography was an effective modality for proper diagnosis. We should be
      concerned of reversible ischemia due to the dissection flap in patients with type
      B aortic dissection. Fenestration of the aorta can be a choice of treatment in
      such patients. The patient has been doing well with no ischemia for 3.5 years
      after the operation. 

PMID- 25848427
TI  - Endovascular Treatment of Iliac Vein Compression (May-Thurner) Syndrome:
      Angioplasty and Stenting with or without Manual Aspiration Thrombectomy and
      Catheter-Directed Thrombolysis.
AB  - PURPOSE: May-Thurner syndrome (MTS) is a rare clinical entity featuring venous
      obstruction of the left lower extremity. The aim of the present study was to
      report our experience with MTS and to evaluate the utility of treatment using
      endovascular techniques. MATERIALS AND METHODS: We retrospectively analyzed data
      on 23 MTS patients (21 females, two males; mean age 44 +/- 15 years). Eighteen
      patients presented with deep vein thrombosis (DVT) and five with symptoms
      associated with chronic venous hypertension (CVH). DVT patients were treated via
      thromboaspiration, catheter-directed thrombolysis, and angioplasty; followed by
      stent placement. CVH patients were treated with angioplasty and stent placement
      alone. All patients were followed-up using Doppler ultrasonography and computed
      tomography venography. RESULTS: Complete left common iliac vein patency was
      achieved in 21 of the 23 patients (technical success rate: 91,3%). Complete
      thrombolysis was attained by 14 of the 18 DVT patients (77.7%). The mean clinical
      and radiological follow-up time was 15.2 +/- 16.1 months. Upon follow-up,
      complete symptomatic regression was observed in 19 of the 23 patients (82.6%).
      Stent patency was complete in 19 of the 21 patients (90.4%) who received stents.
      Restenosis occurred in two patients. No treatment-related mortality or morbidity
      was observed. CONCLUSION: Endovascular treatment of MTS is safe and effective and
      reduces symptoms in most patients, associated with high medium-term patency
      rates.

PMID- 25848429
TI  - Abdominal aortic aneurysm complicated by intestinal malrotation.
AB  - Intestinal malrotation (IM) is an anomaly of fetal intestinal rotation that
      usually presents in the first month of life; it is rare for malrotaion to present
      in adulthood. Furthermore, the presentation of IM in conjunction with Abdominal
      aortic aneurysm is extremely rare and may require consideration with respect to
      the surgical approach and exposure of the abdominal aorta. We herein report a
      case of an abdominal aortic aneurysm complicated by intestinal malrotation. 

PMID- 25848430
TI  - Acute Pulmonary Thromboembolism and Deep Vein Thrombosis during the Medical
      Treatment of Acute Aortic Dissection was Successfully Treated by the Combination
      of Inferior Vena Cava Filter Installation and Anti-Coagulant Therapy: A Case
      Report.
AB  - A 71-year-old woman was admitted with Stanford type A acute aortic dissection
      (AAD). Computed tomography (CT) revealed thrombosis of the false lumen, and we
      planned to treat medically. She developed transient pleural effusion and
      hypoxemia, which persisted despite her pleural effusion disappeared. We performed
      CT and found a large thrombus in the pulmonary artery and femoral vein. We
      administered low dose- unfractionated heparin and installed a retrievable
      inferior vena cava filter, which caused the thrombus in the pulmonary artery to
      disappeared without exacerbating AAD. Our strategy seems to be suitable for acute
      pulmonary thromboembolism that occurs during the treatment of AAD. 

PMID- 25848431
TI  - Ruptured pancreaticoduodenal artery aneurysm associated with median arcuate
      ligament compression and aortic dissection successfully treated with
      embolotherapy.
AB  - A 51-year-old man with a ruptured pancreaticoduodenal artery (PDA) aneurysm
      caused by compression of the celiac artery by the median arcuate ligament and
      aortic dissection involving the celiac axis was transferred to our hospital for
      endovascular treatment. A 4-F catheter was advanced into the superior mesenteric
      artery through the narrow true lumen via the left brachial artery, and coil
      embolization of the aneurysm was successfully performed. In this case, rapid
      increase of blood flow in the superior mesenteric artery, which compensated for
      the decreased celiac blood flow by aortic dissection, increased hemodynamic
      stress on the PDA, leading to aneurysmal rupture. 

PMID- 25848432
TI  - Two dehiscences of the aortic valve commissure and cusp with progressive acute
      aortic regurgitation.
AB  - A 54-year-old female with acute heart failure due to aortic regurgitation (AR)
      was admitted to our hospital. Following admission, her condition worsened
      progressively; thus, surgery was performed prematurely. During surgery, two
      dehiscences were visualized in the aortic valve commissure between the right and
      left cusps and the upper part of the left coronary artery ostium. However we
      scheduled aortic valve replacement (AVR) at first, we made the shift to perform
      the aortic root replacement for reinforcement of the aortic wall around the left
      coronary artery ostium. We describe a rare case of two dehiscences at the aortic
      root, which is the first report. 

PMID- 25848433
TI  - Internal iliac artery aneurysmo-colonic fistula after endovascular stent-graft
      repair: a case report.
AB  - We describe rare ilio-enteric fistula that developed after endovascular repair of
      a left internal iliac artery aneurysm (IIAA). An 83-year-old man with a history
      of previous surgeries via laparotomies suddenly developed a high fever 3 years
      after undergoing endovascular abdominal aortic repair (EVAR) with a stent-graft
      to treat a left isolated IIAA. Computed tomography imaging revealed a fistula
      between the IIAA and the sigmoid colon. A colostomy was created because severe
      intraperitoneal adhesions prevented resection of the IIAA. The postoperative
      course was uneventful and the patient remained free of infection without
      antibiotics. Residual aneurysms can cause complications after EVAR. 

PMID- 25848434
TI  - Ascending aortic false aneurysm formation associated with rupture of acute type a
      aortic dissection.
AB  - A 63-year-old man with ruptured acute type A aortic dissection was referred to
      our hospital. Computed tomography showed a false aneurysm arising from the false
      lumen located beside the ascending aorta. His hemodynamic status was stable
      inspite of the ruptured acute aortic dissection. We consider that the containment
      of the false aneurysm by thin mediastinal structures prevented worsening of his
      hemodynamic status, and this is extremely rare. 

PMID- 25848435
TI  - Open surgical repair for a ruptured abdominal aortic aneurysm with a horseshoe
      kidney.
AB  - Horseshoe kidney is a congenital anomaly characterized by medial fusion of the
      bilateral kidneys. Treatment for an abdominal aortic aneurysm (AAA) with a
      horseshoe kidney is a technical challenge because of the complex anatomy. We
      report a successful open surgical repair for a ruptured AAA with a horseshoe
      kidney. An aortic grafting was performed with division of the renal isthmus
      through a transperitoneal approach. In the case of a ruptured AAA, quick open
      surgery is the most reliable treatment. If a horseshoe kidney coexists,
      transperitoneal approach with division of the renal isthmus provides good
      surgical field for an aortic grafting. 

PMID- 25848436
TI  - Surgical repair for popliteal venous aneurysm causing severe or recurrent
      pulmonary thromboembolism: three case reports.
AB  - Poplitealvenous aneurysms (PVA) are associated with deep venous thrombosis and
      recurrentpulmonary thromboembolism (PE). We report three cases of PVA. In all
      three patients the first sign of PVA was acute PE; in one case, the PE was
      recurrent. Computed tomography and duplex ultrasonography revealed not only PE
      but also popliteal venous dilatation with thrombus. Surgical reconstruction was
      performed in each case after treatment for PE. No postoperative complications
      occurred, including recurrent PE. Surgical repair of PVA is safe and is a
      recommended treatment. 

PMID- 25848437
TI  - Hybrid endovascular repair for an arch aneurysm combined with aberrant right
      subclavian artery.
AB  - This report describes a hybrid endovascular approach to a 9.3-cm saccular
      aneurysm of the left sided aortic arch combined with an aberrant right subclavian
      artery. The two-step procedure consisted of a bilateral carotid-subclavian
      bypass, followed by an ascending aorta-bicarotid bypass and completed by an
      endovascular exclusion of the aneurysm by covering the whole aortic arch and its
      branches. The patient had no postoperative complications and was discharged 10
      postoperative day. Hybrid procedures may be useful in complex aortic arch
      pathologies and may reduce postoperative complications in comparison with
      conventional open surgery. 

PMID- 25848438
TI  - Emergent rescue operation for expanding mycotic pseudoaneurysm causing
      hemoptysis, originating from right subclavian artery.
AB  - Mycotic pseudoaneurysm of the subclavian artery is uncommon and its therapeutic
      strategy has not been established. We report a case of 81-year-old woman with
      mycotic pseudoaneurysm in the right subclavian artery. Blood culture showed
      Enterobacter cloacae. Because of hemoptysis and acute expansion of the
      pseudoaneurysm, emergent coil embolization was performed, but failed. The patient
      underwent urgent operation for an en-bloc resection of the pseudoaneurysm after
      aorto-right common carotid artery bypass followed by omentum packing. The patient
      underwent continuous wound irrigation for 3 weeks. The postoperative course was
      uneventful and without recurrence of infection. 

PMID- 25848439
TI  - Isolated Transverse Clivus Fracture without Neurodeficit: Case Report and Review
      of Literature.
AB  - BACKGROUND: Clivus is a bony surface in the posterior cranial fossa, serving as
      the support of the brainstem and thus neighboring important structures because of
      its location. Skull base fractures that cannot be shown by conventional
      radiography can be clearly imaged by high-resolution bone window computed
      tomography. CASE REPORT: A 44 years-old male referred to the emergency department
      because of a traffic accident in the car. His only complaint was a severe
      neckache. His X-ray examination showed no pathology. The computed tomographic
      examination showed no parenchymal pathology, but a isolated transverse fracture
      in the clivus. CONCLUSIONS: The computed tomographic examination showed isolated
      transverse fracture in the clivus our case presented in this paper is the first
      case of transverse clivus fracture without additional cranial bone fracture and
      neurologic deficit in the literature.

PMID- 25848440
TI  - Embolization of a True Giant Splenic Artery Aneurysm Using NBCA Glue - Case
      Report and Literature Review.
AB  - BACKGROUND: Although splenic artery aneurysms (SAAs) are common, their giant
      forms (more than 10 cm in diameter) are rare. Because of the variety of forms and
      locations of these aneurysms, there are a lot of therapeutic methods to choose.
      In our case of a giant true aneurysm we performed an endovascular embolization
      with N-butyl-cyano-acrylate (NBCA) glue. To our knowledge it is the first
      reported case of this method of treatment of true giant SAA. CASE REPORT: A 74
      year-old male patient with symptomatic giant SAA (13 cm) was urgently admitted to
      our hospital for the diagnostic and therapeutic procedures. Due to the general
      health condition, advanced age and the large size of the aneurysm we decided to
      perform an endovascular treatment with N-butyl-cyano-acrylate (NBCA) glue.
      CONCLUSIONS: The preaneurysmal part of splenic artery was occluded completely
      with exclusion of the aneurysm. No splenectomy was needed. The patient was
      discharged in good general condition Embolization with NBCA can be an efficient
      method to treat the giant SAA.

PMID- 25848441
TI  - Internal carotid artery blister-like aneurysm caused by Aspergillus - case
      report.
AB  - BACKGROUND: Blister-like aneurysm of the supraclinoid internal carotid artery
      (ICA) is a well-documented cause of subarachnoid hemorrhage. Generally, this type
      of aneurysm is associated with various conditions such as hypertension,
      arteriosclerosis, and ICA dissection. Although Aspergillus is the most common
      organism causing intracranial fungal aneurysmal formation, there is no report of
      a blister-like aneurysm caused by Aspergillus infection. CASE REPORT: An 83-year
      old man received corticosteroid pulse therapy followed by oral steroid therapy
      for an inflammatory pseudotumor of the clivus. Two months later, the patient was
      transported to an emergency department due to the diffuse subarachnoid
      hemorrhage, classified as Fisher group 4. Subsequent 3D computed tomography
      angiogram revealed a blister-like aneurysm at the superior wall of the left ICA.
      Six days later, the patient died of subarachnoid hemorrhage caused by the left
      ICA aneurysm rerupture. Autopsy revealed proliferation of Aspergillus hyphae in
      the wall of the aneurysm. Notably, that change was present more densely in the
      inner membrane than in the outer one. Thus, it was considered that Aspergillus
      hyphae caused infectious aneurysm formation in the left ICA via hematogenous
      seeding rather than direct invasion. CONCLUSIONS: The blister-like aneurysm is a
      rare but important cause of subarachnoid hemorrhage. This case report documents
      another cause of blister-like aneurysms, that is an infectious aneurysm
      associated with Aspergillus infection.

PMID- 25848442
TI  - Composite grafting of a distal thumb amputation: a case report and review of
      literature.
AB  - OBJECTIVE: We report a case in which an avulsion-amputation of the thumb proximal
      to the lunula was repaired by reattaching the amputated segment as a composite
      graft. The graft demonstrated complete survival with only a minimal sacrifice in
      length. METHODS: A 23-year-old man presented 4 hours after an avulsion injury of
      the thumb with associated distal and proximal phalanx fractures. The amputated
      segment included the sterile and germinal matrix. He underwent defatting and
      composite grafting of the amputated segment followed by K-wire fixation of his
      proximal phalanx fracture. RESULTS: In his 1-week follow-up, the patient's
      composite graft-including his nail bed-demonstrated complete survival. At one
      month, the composite graft maintained stable soft tissue coverage and showed
      signs of nail plate regrowth. Four months after repair, he was able to return to
      light duty and was advanced to full duty within 5 months. He continued to report
      gradually improving hypersensitivity at the margins of the graft and stiffness of
      the interphalangeal joint. At five months he regained full mobility of his
      carpometacarpal joint. The range of motion of his interphalangeal and
      metacarpophalangeal joint were 0 to 10 degrees and 0 to 25 degrees, respectively.
      He was able to oppose his thumb to all 4 digits. Six months after repair, he
      demonstrated protective sensation of the tip of the thumb. CONCLUSION: Composite
      grafting of the thumb, even in less than ideal cases, can still provide useful
      length for function as a opposable post and can be considered in reconstruction
      of thumb amputations at or proximal to the lunula.

PMID- 25848443
TI  - Fibrous dysplasia: an overview of disease process, indications for surgical
      management, and a case report.
AB  - INTRODUCTION: First described by Von Recklinghausen in 1891, fibrous dysplasia is
      a developmental defect of osseous tissue such that bone is produced with an
      abnormally thin cortex and marrow is replaced with fibrous tissue that
      demonstrates characteristic ground-glass appearance on x-ray examination. The
      underlying defect in fibrous dysplasia is a mutation of the GNAS1 gene, which
      leads to constitutive activation of gene products that preclude the maturation of
      osteoprogenitor cells and lead to development of abnormal bone matrix,
      trabeculae, and collagen, produced by undifferentiated mesenchymal cells. There
      exists a mainly self-limiting form of fibrous dysplasia classified as monostotic,
      which is characterized by dysplastic bone in a single location that remains
      relatively stable throughout life and a polyostotic form, which can exhibit
      aggressive growth placing adjacent structures at risk for compressive sequelae.
      METHODS: We present the surgical management of an unusual case of monostotic
      fibrous dysplasia, which exhibited aggressive growth with mass effect, and late
      presentation, both uncharacteristic features for the monostotic form. The authors
      also performed a comprehensive review of the literature and discuss the disease
      process, management options, and indications for surgical treatment. RESULTS: An
      overview of the disease process and management options is presented. The authors
      also present details of reconstruction in an unusual form of symptomatic
      monostotic fibrous dysplasia. CONCLUSION: Conservative management is usually the
      mainstay of therapy in asymptomatic cases of fibrous dysplasia. In patients
      fulfilling criteria for surgical management, craniofacial reconstruction offers a
      viable option in the surgeon's armamentarium, providing good functional and
      cosmetic outcomes.

PMID- 25848444
TI  - Lymphatic mapping in the treatment of chronic seroma: a case series.
AB  - OBJECTIVE: Seromas or lymphoceles are common postoperative complications. This
      series presents 3 patients with lower extremity seromas refractory to treatment
      that required lymphatic mapping and lymphatic ligation for closure, and in 1
      case, diagnosis. METHODS: Lymphatic mapping procedure consisted of intraoperative
      injection of subcutaneous tissue with methylene blue distal to the seroma with
      observation of dye effluence from transected or injured lymphatics draining into
      area of seroma. RESULTS: In 2 patients, methylene blue dye absorption into
      lymphatic vessels allowed for optimized visual identification of lymphatic leak
      and contrast against surrounding tissues. In the third patient, where no
      lymphocele leak was found, the study was diagnostic and helped to find an
      alternate etiology for the recurrent seroma. CONCLUSION: Lymphatic mapping with
      methylene blue dye is an effective tool in the evaluation and diagnosis of
      chronic seroma.

PMID- 25848445
TI  - Longitudinal slit procedure in addition to negative pressure wound therapy for a
      refractory wound with exposed achilles tendon.
AB  - OBJECTIVE: This case report reviews features of negative pressure wound therapy,
      particularly for the exposed Achilles tendon, and describes an additional
      effective procedure. METHODS: An 87-year-old man presented with a soft-tissue
      defect measuring 3*5 cm with the exposed Achilles tendon as a sequela of deep
      burn. The condition of his affected leg was ischemic because of arteriosclerosis.
      We used negative pressure wound therapy and made 2 longitudinal slits penetrating
      the tendon to induce blood flow from the ventral side to the dorsal surface.
      RESULTS: By this combination therapy, the surface of the exposed Achilles tendon
      was completely epithelialized and the tendon was spared without disuse syndrome.
      CONCLUSIONS: The authors conclude that this combination therapy is useful for
      covering the widely exposed tendon in aged patients.

PMID- 25848446
TI  - Cement burn.

PMID- 25848447
TI  - [Renal, pancreatic and adrenal masses].

PMID- 25848448
TI  - [Histopathological study of cervical lymphadenopathy in Yaounde, Cameroon].

PMID- 25848449
TI  - [One case of vitreous asteroid degeneration].

PMID- 25848450
TI  - [Salivary gland tumors, clinico-epidemiological study and radioanatomy
      correlation: retrospective study of 148 cases].

PMID- 25848451
TI  - Mammary-like adenocarcinoma of the vulva associated to Paget's disease: a case
      report.
AB  - Mammary-like adenocarcinoma of the vulva associated to Paget's disease is
      exceedingly rare. So, it is very important to perform all the pathological and
      immunohistochemical investigations to achieve differential diagnosis from both a
      metastatic lesion from an orthotopic breast cancer and a vulvar adnexal tumor.
      This report describes a case of vulvar Paget's disease associated with underlying
      mammary-like adenocarcinoma diagnosed in the Department of Obstetrics and
      Gynecology of Farhat Hached university hospital of Sousse in Tunisia. We also
      review previously reported cases of primary breast-like carcinoma of the vulva
      with or without Paget's disease. 

PMID- 25848452
TI  - [Scarf osteotomy in the treatment of hallux valgus: about 19 cases].

PMID- 25848453
TI  - [Influence of caretakers' behavior on the quality of life of patients admitted
      for upper gastrointestinal bleeding in Lome campus University Hospital (Togo)].

PMID- 25848454
TI  - [Chilaiditi syndrome in a newborn, in a case report].

PMID- 25848455
TI  - Ambulatory blood pressure measurement in the main cities of Cameroon: prevalence
      of masked and white coat hypertension, and influence of body mass index.
AB  - INTRODUCTION: Identifying White Coat Hypertension (WCH) may avoid inappropriate
      commitment of individuals to lifelong and costly blood pressure (BP) lowering
      medications'. We assessed the prevalence and determinants of WCH in urban
      clinical settings in Cameroon. METHODS: Participants were a consecutive sample of
      adults, who underwent ambulatory BP measurements (ABPM) for the diagnosis of
      hypertension and evaluation of treatmentin three referral cardiac clinics in the
      cities of Yaounde and Douala, between January 2006 and July 2011. WCH was defined
      as an office-based systolic (or diastolic) BP >= 140(90) mmHg together with an
      average day time ambulatory systolic (and diastolic) BP < 135(85) mmHg. RESULTS:
      Of the 500 participants included, 188 (37.6%) were women, 230 (46%) were
      nonsmokers and 53 (10.6%) had diabetes mellitus. The mean age was 51.6+/-10.2
      years. The ABPM readings were higher in men than in women (p<0.05).The prevalence
      of WCH was 26.4% overall, 39.3% in women and 22.4% in men (p=0.01).In
      multivariable analysis, body mass index was the only significant determinant of
      WCH (Odds ratio= 1.15(95% confidence intervals: 1.00-1.43), p<0.05). CONCLUSION:
      The prevalence of WCH was high in our study population and was correlated only
      with BMI. Accurate measurement of BP and appropriate diagnosis of hypertension
      using ABPM in this setting may help limiting the consequences of over estimating
      hypertension severity on individuals, families and health systems.

PMID- 25848456
TI  - Plasma oxidized low density lipoprotein cholesterol correlates inversely with
      testosterone in young adult male smokers.
AB  - INTRODUCTION: There are indications that oxidized low density lipoprotein
      cholesterol (Ox-LDLC) may play an important role in cardiovascular disease (CVD)
      events. In most developing countries, the interplay between the different lipid
      fractions and cigarette smoking has not been studied. This study assessed the
      effect of cigarette smoking on the alterations in plasma lipid fractions and
      their associations with the gonadal hormone, testosterone (T). METHODS: One
      hundred and sixty male participants, consisting of eighty smokers and eighty
      apparently healthy non-smokers were recruited. Anthropometric indices and
      biochemical parameters were determined using standard procedures. RESULTS:
      Significant increases were obtained in plasma total cholesterol (TC),
      triglyceride (TG), oxidized low density lipoprotein (Ox-LDLC) and Ox-LDLC/TT
      ratio (p<0.001) in smokers compared with the non-smokers. Plasma high density
      cholesterol (HDLC) (p<0.001) was significantly reduced in smokers compared with
      the non-smokers. The plasma mean T result was not significantly different from
      the non-smokers, but inversely correlated with Ox-LDLC and significantly
      correlated with the lipids and lipoproteins. Significantly high plasma TC, TG and
      LDLC (p<0.001) and low HDLC (p<0.001) were also obtained in smokers when co
      founding factors such as duration and number of cigarette smoked per day were
      applied. CONCLUSION: This study showed an inverse correlation between Ox-LDLC and
      testosterone as well as strong association between the number of tobacco and
      cigarettes usage per day. These changes in part, could be major causes of
      premature CVD and decreased fertility in young adults.

PMID- 25848457
TI  - [Traumatic compression syndrome: report of a case].

PMID- 25848458
TI  - Environmental surveillance of poliovirus and non-polio enterovirus in urban
      sewage in Dakar, Senegal (2007-2013).
AB  - INTRODUCTION: Global poliomyelitis eradication initiative relies on (i)
      laboratory based surveillance of acute flaccid surveillance (AFP) to monitor the
      circulation of wild poliovirus in a population, and (ii) vaccination to prevent
      its diffusion. However, as poliovirus can survive in the environment namely in
      sewage, environmental surveillance (ES) is of growing importance as the
      eradication target is close. This study aimed to assess polioviruses and non
      polio enteroviruses circulation in sewage drains covering a significant
      population of Dakar. METHODS: From April 2007 to May 2013, 271 specimens of raw
      sewage were collected using the grab method in 6 neighborhoods of Dakar. Samples
      were processed to extract and concentrate viruses using polyethylene glycol and
      Dextran (two-phase separation method). Isolation of enteroviruses was attempted
      in RD, L20B and Hep2 cell lines. Polioviruses were identified by RT-PCR and
      Elisa. Non Polio Enteroviruses (NPEVs) were identified by RT-PCR and
      microneutralisation tests. RESULTS: Polioviruses and NPEVs were respectively
      detected in 34,3% and 42,8% sewage samples. No wild poliovirus neither
      circulating vaccine-derived Poliovirus (cVDPV) was detected. Neutralization
      assays have identified 49 non polio enteroviruses that were subsequently
      classified in 13 serotypes belonging to HEV-A (22, 4%), HEV-B (12, 24%), HEV-C
      (26, 53%) and HEV-D (6, 12%) species. CONCLUSION: This study is the first
      documentation of enteroviruses environmental detection in Senegal. It shows the
      usefulness of environmental surveillance for indirect monitoring of the
      circulation and distribution of enteroviruses in the community.

PMID- 25848459
TI  - Genotypes and viral variants in chronic hepatitis B: A review of epidemiology and
      clinical relevance.
AB  - The Hepatitis B Virus (HBV) has a worldwide distribution and is endemic in many
      populations. It is constantly evolving and 10 genotypic strains have been
      identified with varying prevalences in different geographic regions. Numerous
      stable mutations in the core gene and in the surface gene of the HBV have also
      been identified in untreated HBV populations. The genotypes and viral variants
      have been associated with certain clinical features of HBV related liver disease
      and Hepatocellular carcinoma. For example Genotype C is associated with later
      hepatitis B e antigen (HBeAg) seroconversion, and more advanced liver disease.
      Genotype A is associated with a greater risk of progression to chronicity in
      adult acquired HBV infections. Genotype D is particularly associated with the
      precore mutation and HBeAg negative chronic hepatitis B (CHB). The genotypes
      prevalent in parts of West Africa, Central and South America, E, F and H
      respectively, are less well studied. Viral variants especially the Basal Core
      Promotor mutation is associated with increased risk of fibrosis and cancer of the
      liver. Although not currently part of routine clinical care, evaluation of
      genotype and viral variants may provide useful adjunctive information in
      predicting risk about liver related morbidity in patients with CHB. 

PMID- 25848460
TI  - Spontaneous bacterial peritonitis: The clinical challenge of a leaky gut and a
      cirrhotic liver.
AB  - Spontaneous bacterial peritonitis (SBP) is a frequent, life-threatening bacterial
      infection in patients with liver cirrhosis and ascites. Portal hypertension leads
      to increased bacterial translocation from the intestine. Failure to eliminate
      invading pathogens due to immune defects associated with advanced liver disease
      on the background of genetic predisposition may result in SBP. The efficacy of
      antibiotic treatment and prophylaxis has declined due to the spread of multi
      resistant bacteria. Patients with nosocomial SBP and with prior antibiotic
      treatment are at a particularly high risk for infection with resistant bacteria.
      Therefore, it is important to adapt empirical treatment to these risk factors and
      to the local resistance profile. Rifaximin, an oral, non-absorbable antibiotic,
      has been proposed to prevent SBP, but may be useful only in a subset of patients.
      Since novel antibiotic classes are lacking, we have to develop prophylactic
      strategies which do not induce bacterial resistance. Farnesoid X receptor
      agonists may be a candidate, but so far, clinical studies are not available. New
      diagnostic tests which can be carried out quickly at the patient's site and
      provide additional prognostic information would be helpful. Furthermore, we need
      tools to predict antibiotic resistance in order to tailor first-line antibiotic
      treatment of spontaneous bacterial peritonitis to the individual patient and to
      reduce mortality. 

PMID- 25848461
TI  - Non-alcoholic fatty liver disease and psoriasis: So far, so near.
AB  - Psoriasis is a chronic inflammatory immune-mediated skin diseases which is
      frequently associated to comorbidities. Non-alcoholic fatty liver disease (NAFLD)
      is defined as an excessive accumulation of triglycerides in hepatocytes and
      includes a wide spectrum of liver conditions ranging from relatively benign
      steatosis to non-alcoholic steatohepatitis with fatty infiltration and lobular
      inflammation and to cirrhosis and end-stage liver disease. Actually, psoriasis is
      considered a systemic diseases associated to comorbidities, as metabolic syndrome
      and NAFLD is seen the hepatic manifestation of the metabolic syndrome. The
      possible link between psoriasis, obesity and metabolic syndrome, which are known
      risk factors for NAFLD has been recently documented focusing in the crucial role
      of the adipose tissue in the development of the inflammatory background sharing
      by the above entities. According to recent data, patients with psoriasis show a
      greater prevalence of NAFLD and metabolic syndrome than the general population.
      Moreover, patients with NAFLD and psoriasis are at higher risk of severe liver
      fibrosis than those with NAFLD and without psoriasis. The link between these
      pathological conditions appears to be a chronic low-grade inflammatory status.
      The aim of this review is to focus on the multiple aspects linking NAFLD and
      psoriasis, only apparently far diseases. 

PMID- 25848462
TI  - Hepatitis C virus syndrome: A constellation of organ- and non-organ specific
      autoimmune disorders, B-cell non-Hodgkin's lymphoma, and cancer.
AB  - The clinical course of chronic hepatitis C virus (HCV) infection is characterized
      by possible development of both liver and extrahepatic disorders. The tropism of
      HCV for the lymphoid tissue is responsible for several immune-mediated disorders;
      a poly-oligoclonal B-lymphocyte expansion, commonly observed in a high proportion
      of patients with HCV infection, are responsible for the production of different
      autoantibodies and immune-complexes, such as mixed cryoglobulins. These
      serological alterations may characterize a variety of autoimmune or neoplastic
      diseases. Cryoglobulinemic vasculitis due to small-vessel deposition of
      circulating mixed cryoglobulins is the prototype of HCV-driven immune-mediated
      and lymphoproliferative disorders; interestingly, in some cases the disease may
      evolve to frank malignant lymphoma. In addition, HCV shows an oncogenic potential
      as suggested by several clinico-epidemiological and laboratory studies; in
      addition to hepatocellular carcinoma that represents the most frequent HCV
      related malignancy, a causative role of HCV has been largely demonstrated in a
      significant percentage of patients with isolated B-cells non-Hodgkin's lymphomas.
      The same virus may be also involved in the pathogenesis of papillary thyroid
      cancer, a rare neoplastic condition that may complicate HCV-related thyroid
      involvement. Patients with HCV infection are frequently asymptomatic or may
      develop only hepatic alteration, while a limited but clinically relevant number
      can develop one or more autoimmune and/or neoplastic disorders. Given the large
      variability of their prevalence among patients' populations from different
      countries, it is possible to hypothesize a potential role of other co-factors,
      i.e., genetic and/or environmental, in the pathogenesis of HCV-related extra
      hepatic diseases. 

PMID- 25848463
TI  - Risk of hepatitis B virus reactivation in rheumatoid arthritis patients
      undergoing biologic treatment: Extending perspective from old to newer drugs.
AB  - Hepatitis B virus (HBV) reactivation in rheumatoid arthritis (RA) patients
      undergoing biological therapy is not infrequent. This condition can occur in
      patients with chronic hepatitis B as well as in patients with resolved HBV
      infection. Current recommendations are mainly focused on prevention and
      management strategies of viral reactivation under tumor necrosis factor-alpha
      inhibitors or chimeric monoclonal antibody rituximab. In recent years, growing
      data concerning HBV reactivation in RA patients treated with newer biological
      drugs like tocilizumab and abatacept have cumulated. In this review,
      epidemiology, pathogenesis and natural history of HBV infection have been revised
      first, mainly focusing on the role that specific therapeutic targets of current
      biotechnological drugs play in HBV pathobiology; finally we have summarized
      current evidences from scientific literature, including either observational
      studies and case reports as well, concerning HBV reactivation under different
      classes of biological drugs in RA patients. Taking all these evidences into
      account, some practical guidelines for screening, vaccination, prophylaxis and
      treatment of HBV reactivation have been proposed. 

PMID- 25848464
TI  - Diagnosis and treatment of hepatocellular carcinoma: An update.
AB  - Hepatocellular carcinoma (HCC) is one of the most common malignancies leading to
      high mortality rates in the general population; in cirrhotic patients, it is the
      primary cause of death. The diagnosis is usually delayed in spite of at-risk
      population screening recommendations, i.e., patients infected with hepatitis B or
      C virus. Hepatocarcinogenesis hinges on a great number of genetic and molecular
      abnormalities that lead to tumor angiogenesis and foster their dissemination
      potential. The diagnosis is mainly based on imaging studies such as computed
      tomography and magnetic resonance, in which lesions present a characteristic
      classical pattern of early arterial enhancement followed by contrast medium
      "washout" in late venous phase. On occasion, when imaging studies are not
      conclusive, biopsy of the lesion must be performed to establish the diagnosis.
      The Barcelona Clinic Liver Cancer staging method is the most frequently used
      worldwide and recommended by the international guidelines of HCC management.
      Currently available treatments include tumor resection, liver transplant,
      sorafenib and loco-regional therapies (alcoholization, radiofrequency ablation,
      chemoembolization). The prognosis of hepatocarcinoma is determined according to
      the lesion's stage and in cirrhotic patients, on residual liver function.
      Curative treatments, such as liver transplant, are sought in patients diagnosed
      in early stages; patients in more advanced stages, were not greatly benefitted by
      chemotherapy in terms of survival until the advent of target molecules such as
      sorafenib. 

PMID- 25848465
TI  - Angiogenesis and liver fibrosis.
AB  - Recent data indicate that hepatic angiogenesis, regardless of the etiology, takes
      place in chronic liver diseases (CLDs) that are characterized by inflammation and
      progressive fibrosis. Because anti-angiogenic therapy has been found to be
      efficient in the prevention of fibrosis in experimental models of CLDs, it is
      suggested that blocking angiogenesis could be a promising therapeutic option in
      patients with advanced fibrosis. Consequently, efforts are being directed to
      revealing the mechanisms involved in angiogenesis during the progression of liver
      fibrosis. Literature evidences indicate that hepatic angiogenesis and fibrosis
      are closely related in both clinical and experimental conditions. Hypoxia is a
      major inducer of angiogenesis together with inflammation and hepatic stellate
      cells. These profibrogenic cells stand at the intersection between inflammation,
      angiogenesis and fibrosis and play also a pivotal role in angiogenesis. This
      review mainly focuses to give a clear view on the relevant features that
      communicate angiogenesis with progression of fibrosis in CLDs towards the-end
      point of cirrhosis that may be translated into future therapies. The pathogenesis
      of hepatic angiogenesis associated with portal hypertension, viral hepatitis, non
      alcoholic fatty liver disease and alcoholic liver disease are also discussed to
      emphasize the various mechanisms involved in angiogenesis during liver
      fibrogenesis. 

PMID- 25848466
TI  - Cirrhosis in children and adolescents: An overview.
AB  - Several conditions, especially chronic liver diseases, can lead to cirrhosis in
      children and adolescents. Most cases in clinical practice are caused by similar
      etiologies. In infants, cirrhosis is most often caused by biliary atresia and
      genetic-metabolic diseases, while in older children, it tends to result from
      autoimmune hepatitis, Wilson's disease, alpha-1-antitrypsin deficiency and
      primary sclerosing cholangitis. The symptoms of cirrhosis in children and
      adolescents are similar to those of adults. However, in pediatric patients, the
      first sign of cirrhosis is often poor weight gain. The complications of pediatric
      cirrhosis are similar to those observed in adult patients, and include
      gastrointestinal bleeding caused by gastroesophageal varices, ascites and
      spontaneous bacterial peritonitis. In pediatric patients, special attention
      should be paid to the nutritional alterations caused by cirrhosis, since children
      and adolescents have higher nutritional requirements for growth and development.
      Children and adolescents with chronic cholestasis are at risk for several
      nutritional deficiencies. Malnutrition can have severe consequences for both pre-
      and post-liver transplant patients. The treatment of cirrhosis-induced portal
      hypertension in children and adolescents is mostly based on methods developed for
      adults. The present article will review the diagnostic and differential
      diagnostic aspects of end-stage liver disease in children, as well as the major
      treatment options for this condition. 

PMID- 25848467
TI  - Staging systems for hepatocellular carcinoma: Current status and future
      perspectives.
AB  - Hepatocellular carcinoma (HCC) is a major health concern worldwide and the third
      cause of cancer-related death. Despite advances in treatment as well as careful
      surveillance programs, the mortality rates in most countries are very high. In
      contrast to other cancers, the prognosis and treatment of HCC depend on the tumor
      burden in addition to patient's underlying liver disease and liver functional
      reserve. Moreover, there is considerable geographic and institutional variation
      in both risk factors attributable to the underlying liver diseases and the
      management of HCC. Therefore, although many staging and/or scoring systems have
      been proposed, there is currently no globally accepted system for HCC due to the
      extreme heterogeneity of the disease. The aim of this review is to focus on
      currently available staging systems as well as those newly reported in the
      literatures since 2012. Moreover, we describe problems with currently available
      staging systems and attempts to modify and/or add variables to existing staging
      systems. 

PMID- 25848468
TI  - Gut-liver axis in liver cirrhosis: How to manage leaky gut and endotoxemia.
AB  - A "leaky gut" may be the cutting edge for the passage of toxins, antigens or
      bacteria into the body, and may play a pathogenic role in advanced liver
      cirrhosis and its complications. Plasma endotoxin levels have been admitted as a
      surrogate marker of bacterial translocation and close relations of endotoxemia to
      hyperdynamic circulation, portal hypertension, renal, cardiac, pulmonary and
      coagulation disturbances have been reported. Bacterial overgrowth, increased
      intestinal permeability, failure to inactivate endotoxin, activated innate
      immunity are all likely to play a role in the pathological states of bacterial
      translocation. Therapeutic approach by management of the gut-liver axis by
      antibiotics, probiotics, synbiotics, prebiotics and their combinations may
      improve the clinical course of cirrhotic patients. Special concern should be paid
      on anti-endotoxin treatment. Adequate management of the gut-liver axis may be
      effective for prevention of liver cirrhosis itself by inhibiting the progression
      of fibrosis. 

PMID- 25848470
TI  - Gender-based disparities in access to and outcomes of liver transplantation.
AB  - Despite comprising 35% of transplants, the number of female transplant recipients
      has continued to decline. Accordingly, there is a growing attention to the issue
      of access to and outcomes of liver transplantation in women. The purpose of this
      review is to critically evaluate the published literature on etiologies
      contributing to gender-based disparities in liver transplantation focusing on the
      steps from chronic liver disease through transplantation including disparities in
      liver disease prevalence, access to liver transplant centers and transplant
      waiting list, receipt of liver transplantation once listed and disparities in
      post-liver transplantation outcomes. Our review finds factors contributing to
      this disparity may include gender differences in the etiology of underlying liver
      disease and patient and physician referral patterns, lifestyle and health care,
      but also utilization of an imperfect organ allocation system based on the model
      for end stage liver disease score and donor-recipient liver size matching. The
      review also highlights the need for further research in the area of gender
      disparity in order to develop appropriate approaches to address it and to improve
      allocation of this precious resource in the future. 

PMID- 25848469
TI  - Endothelial dysfunction in cirrhosis: Role of inflammation and oxidative stress.
AB  - This review describes the recent developments in the pathobiology of endothelial
      dysfunction (ED) in the context of cirrhosis with portal hypertension and defines
      novel strategies and potential targets for therapy. ED has prognostic
      implications by predicting unfavourable early hepatic events and mortality in
      patients with portal hypertension and advanced liver diseases. ED characterised
      by an impaired bioactivity of nitric oxide (NO) within the hepatic circulation
      and is mainly due to decreased bioavailability of NO and accelerated degradation
      of NO with reactive oxygen species. Furthermore, elevated inflammatory markers
      also inhibit NO synthesis and causes ED in cirrhotic liver. Therefore,
      improvement of NO availability in the hepatic circulation can be beneficial for
      the improvement of endothelial dysfunction and associated portal hypertension in
      patients with cirrhosis. Furthermore, therapeutic agents that are identified in
      increasing NO bioavailability through improvement of hepatic endothelial nitric
      oxide synthase (eNOS) activity and reduction in hepatic asymmetric
      dimethylarginine, an endogenous modulator of eNOS and a key mediator of elevated
      intrahepatic vascular tone in cirrhosis would be interesting therapeutic
      approaches in patients with endothelial dysfunction and portal hypertension in
      advanced liver diseases. 

PMID- 25848471
TI  - Magnetic resonance imaging of the cirrhotic liver: An update.
AB  - Noninvasive imaging has become the standard for hepatocellular carcinoma (HCC)
      diagnosis in cirrhotic livers. In this review paper, we go over the basics of MR
      imaging in cirrhotic livers and describe the imaging appearance of a spectrum of
      hepatic nodules marking the progression from regenerative nodules to low- and
      high-grade dysplastic nodules, and ultimately to HCCs. We detail and illustrate
      the typical imaging appearances of different types of HCC including focal, multi
      focal, massive, diffuse/infiltrative, and intra-hepatic metastases; with emphasis
      on the diagnostic value of MR in imaging these lesions. We also shed some light
      on liver imaging reporting and data system, and the role of different magnetic
      resonance imaging (MRI) contrast agents and future MRI techniques including the
      use of advanced MR pulse sequences and utilization of hepatocyte-specific MRI
      contrast agents, and how they might contribute to improving the diagnostic
      performance of MRI in early stage HCC diagnosis. 

PMID- 25848472
TI  - Hepatitis B in healthcare workers: Transmission events and guidance for
      management.
AB  - Hepatitis B virus (HBV) is the most efficiently transmissible of the bloodborne
      viruses that are important in healthcare settings. Healthcare workers (HCWs) are
      at risk for exposure to HBV from infected patients and, if infected, are
      similarly at risk of transmitting HBV to patients. Published cases of HBV
      transmission from HCW to patient are relatively rare, having decreased in
      frequency following the introduction of standard (universal) precautions,
      adoption of enhanced percutaneous injury precautions such as double-gloving in
      surgery, and routine HBV vaccination of HCWs. Here we review published cases of
      HCW-to-patient transmission of HBV, details of which have helped to guide the
      creation of formal guidelines for the management of HBV-infected HCWs. We also
      compare the published guidelines for the management of HBV-infected HCWs from
      various governing bodies, focusing on their differences with regard to
      vaccination requirements, viral load limits, frequency of monitoring, and
      restrictions on practice. Importantly, while there are differences among the
      recommendations from governing bodies, no guidelines uniformly restrict HBV
      infected HCWs from performing invasive or exposure-prone procedures. 

PMID- 25848473
TI  - MiR-122 in hepatitis B virus and hepatitis C virus dual infection.
AB  - Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are the most
      common causes of chronic liver diseases and hepatocelluar carcinomas. Over the
      past few years, the liver-enriched microRNA-122 (miR-122) has been shown to
      differentially regulate viral replication of HBV and HCV. It is notable that the
      level of miR-122 is positively and negatively regulated by HCV and HBV,
      respectively. Consistent with the well-documented phenomenon that miR-122
      promotes HCV accumulation, inhibition of miR-122 has been shown as an effective
      therapy for the treatment of HCV infection in both chimpanzees and humans. On the
      other hand, miR-122 is also known to block HBV replication, and HBV has recently
      been shown to inhibit miR-122 expression; such a reciprocal inhibition between
      miR-122 and HBV suggests an intriguing possibility that miR-122 replacement may
      represent a potential therapy for treatment of HBV infection. As HBV and HCV have
      shared transmission routes, dual infection is not an uncommon scenario, which is
      associated with more advanced liver disease than either HBV or HCV mono
      infection. Thus, there is a clear need to further understand the interaction
      between HBV and HCV and to delineate the role of miR-122 in HBV/HCV dual
      infection in order to devise effective therapy. This review summarizes the
      current understanding of HBV/HCV dual infection, focusing on the pathobiological
      role and therapeutic potential of miR-122. 

PMID- 25848474
TI  - Cirrhotic cardiomyopathy: Implications for the perioperative management of liver
      transplant patients.
AB  - Cirrhotic cardiomyopathy is a disease that has only recently been recognised as a
      definitive clinical entity. In the setting of liver cirrhosis, it is
      characterized by a blunted inotropic and chronotropic response to stress,
      impaired diastolic relaxation of the myocardium and prolongation of the QT
      interval in the absence of other known cardiac disease. A key pathological
      feature is the persistent over-activation of the sympathetic nervous system in
      cirrhosis, which leads to down-regulation and dysfunction of the beta-adrenergic
      receptor. Diagnosis can be made using a combination of echocardiography (resting
      and stress), tissue Doppler imaging, cardiac magnetic resonance imaging, 12-lead
      electrocardiogram and measurement of biomarkers. There are significant
      implications of cirrhotic cardiomyopathy in a number of clinical situations in
      which there is an increased physiological demand, which can lead to acute cardiac
      decompensation and heart failure. Prior to transplantation there is an increased
      risk of hepatorenal syndrome, cardiac failure following transjugular intrahepatic
      portosystemic shunt insertion and increased risk of arrhythmias during acute
      gastrointestinal bleeding. Liver transplantation presents the greatest
      physiological challenge with a further risk of acute cardiac decompensation. Peri
      operative management should involve appropriate choice of graft and minimization
      of large fluctuations in preload and afterload. The avoidance of cardiac failure
      during this period has important prognostic implications, as there is evidence to
      suggest a long-term resolution of the abnormalities in cirrhotic cardiomyopathy. 

PMID- 25848475
TI  - Recommendations for the use of chemoembolization in patients with hepatocellular
      carcinoma: Usefulness of scoring system?
AB  - Several hepatocellular carcinoma (HCC) staging systems have been established, and
      a variety of country-specific treatment strategies are also proposed. The
      barcelona - clinic liver cancer (BCLC) system is the most widely used in Europe.
      The Hong Kong liver Cancer is a new prognostic staging system; it might become
      the reference system in Asia. Transarterial chemoembolization (TACE) is the most
      widely used treatment for HCC worldwide; but it showed a benefit only for
      intermediate stage HCC (BCLC B), and there is still no consensus concerning
      treatment methods and treatment strategies. In view of the highly diverse nature
      of HCC and practices, a scoring system designed to assist with decision making
      before the first TACE is performed or prior to repeating the procedure would be
      highly useful. 

PMID- 25848476
TI  - Hepatitis C virus reinfection after liver transplant: New chances and new
      challenges in the era of direct-acting antiviral agents.
AB  - The first interferon-free regimens have been approved for the treatment of
      patients with chronic hepatitis C virus (HCV). In the liver transplant (LT)
      setting, these regimens are expected to have an important effect, because graft
      loss due to HCV recurrence is a serious problem after LT. The response to the
      hitherto conventional treatment with pegylated interferon and ribavirin is poor.
      The significantly better response rates achieved with boceprevir-based and
      telaprevir-based triple therapy have led to better graft and patient survival
      rates, but severe drug interactions with immunosuppressants limit the feasibility
      of this therapy for LT patients. With the approval of sofosbuvir in January 2014,
      of simeprevir in May 2014, and of daclatasvir in August 2014, three antiviral
      agents are now available and promise to be applicable without relevant adverse
      effects or negative interactions with immunosuppressants. Thus, 2014 marks the
      beginning of a new era of treatment options for HCV recurrence after LT. Although
      safety and efficacy studies of several interferon-free regimens for patients with
      HCV recurrence after LT have achieved good preliminary results, reports of
      clinical experiences with LT patients are scarce. The lack of randomized studies,
      the small number of enrolled and carefully selected patients, and the
      heterogeneity of these studies make the results questionable. Real-life
      experiences are eagerly awaited so that clinicians can estimate the usefulness
      and the pitfalls of these new regimens. Additionally, the high costs of these
      agents may limit their accessibility for many patients. The aim of this review is
      to summarize the current experience with and the expectations of the new direct
      acting antiviral agents for LT patients. 

PMID- 25848477
TI  - Hepatitis B and immunosuppressive therapies for chronic inflammatory diseases:
      When and how to apply prophylaxis, with a special focus on corticosteroid
      therapy.
AB  - Currently immunosuppressive and biological agents are used in a more extensive
      and earlier way in patients with inflammatory bowel disease, rheumatic or
      dermatologic diseases. Although these drugs have shown a significant clinical
      benefit, the safety of these treatments is a challenge. Hepatitis B virus (HBV)
      reactivations have been reported widely, even including liver failure and death,
      and it represents a deep concern in these patients. Current guidelines recommend
      to pre-emptive therapy in patients with immunosuppressants in general, but
      preventive measures focused in patients with corticosteroids and inflammatory
      diseases are scarce. Screening for HBV infection should be done at diagnosis. The
      patients who test positive for hepatitis B surface antigen, but do not meet
      criteria for antiviral treatment must receive prophylaxis before undergoing
      immunosuppression, including corticosteroids at higher doses than prednisone 20
      mg/d during more than two weeks. Tenofovir and entecavir are preferred than
      lamivudine because of their better resistance profile in long-term
      immunosuppressant treatments. There is not a strong evidence, to make a general
      recommendation on the necessity of prophylaxis therapy in patients with
      inflammatory diseases that are taking low doses of corticosteroids in short term
      basis or low systemic bioavailability corticosteroids such as budesonide or
      beclomethasone dipropionate. In these cases regularly HBV DNA monitoring is
      recommended, starting early antiviral therapy if DNA levels begin to rise. In
      patients with occult or resolved hepatitis the risk of reactivation is much
      lower, and excepting for Rituximab treatment, the prophylaxis is not necessary. 

PMID- 25848478
TI  - Hepatitis C in hemodialysis patients.
AB  - Despite reduction of hepatitis C prevalence after recognition of the virus and
      testing of blood products, hemodialysis (HD) patients still comprise a high risk
      group. The natural history of hepatitis C virus (HCV) infection in dialysis is
      not fully understood while the clinical outcome differs from that of the general
      population. HD patients show a milder liver disease with lower aminotransferase
      and viral levels depicted by milder histological features on liver biopsy.
      Furthermore, the "silent" clinical course is consistent with a slower disease
      progression and a lower frequency of cirrhosis and hepatocellular carcinoma.
      Potential explanations for the "beneficial" impact of uremia and hemodialysis on
      chronic HCV infection are impaired immunosurveillance leading to a less
      aggressive host response to the virus and intradialytic release of
      "hepatoprotective" cytokines such as interferon (IFN)-alpha and hepatocyte growth
      factor. However, chronic hepatitis C is associated with a higher liver disease
      related cardiovascular and all-cause mortality of HD patients. Therapy is
      indicated in selected patients groups including younger patients with low
      comorbidity burden and especially renal transplant candidates, preferably after
      performance of a liver biopsy. According to current recommendations, choice of
      treatment is IFN or pegylated interferon with a reported sustained viral response
      at 30%-40% and a withdrawal rate ranging from 17% to 30%. New data regarding
      combination therapy with low doses of ribavirin which provide higher standard
      variable rates and good safety results, offer another therapeutic option. The new
      protease inhibitors may be the future for HCV infected HD patients, though data
      are still lacking. 

PMID- 25848479
TI  - Probiotics as a complementary therapeutic approach in nonalcoholic fatty liver
      disease.
AB  - Nonalcoholic fatty liver disease (NAFLD) is currently recognized as one of the
      most common causes of chronic liver disease. It involves a spectrum of conditions
      that include pure steatosis without inflammation, steatohepatitis, fibrosis and
      cirrhosis. The key factor in the pathophysiology of NAFLD is insulin resistance
      that determines lipid accumulation in the hepatocytes and, thus, oxidative
      stress, which is followed by inflammatory response. However, NAFLD pathogenesis
      is still largely unknown and has been extensively investigated. Although life
      style modification with the aim of losing weight has been advocated to treat this
      disorder, its effectiveness is limited; additionally, there is no specific
      pharmacologic treatment until nowadays. Recent evidence suggests that the gut
      microbiota may play a role in the development of insulin resistance, hepatic
      steatosis, necroinflammation and fibrosis. Differences in gut microbiota between
      NAFLD patients and lean individuals as well as presence of small intestinal
      bacterial overgrowth in NAFLD subjects have been demonstrated. Furthermore, some
      data indicate that the immunoregulatory effects of probiotics may be beneficial
      in NAFLD treatment as they modulate the intestinal microbiota; improve epithelial
      barrier function and strengthen the intestinal wall decreasing its permeability;
      reduce bacterial translocation and endotoxemia; improve intestinal inflammation;
      and reduce oxidative and inflammatory liver damage. In this article, we review
      the clinical trials on the use of probiotics in the treatment of NAFLD and
      discuss the effects of these agents and their efficacy as an emerging therapeutic
      resource to treat NAFLD patients. 

PMID- 25848480
TI  - Treatment of hepatocellular carcinoma: Steps forward but still a long way to go.
AB  - Hepatocellular carcinoma (HCC) is the fifth most common malignancy and the third
      cause of tumor associated deaths worldwide. HCC incidence rates are increasing in
      many parts of the world including developing and developed countries. Potentially
      curative treatments for HCC are resection and liver transplantation, but these
      are only suitable for patients with small tumors, meeting strict pre-defined
      criteria, or well-compensated liver disease. Early diagnosis of HCC can be
      achieved by surveillance of at-risk populations. For patients with non-resectable
      disease treatments modalities include loco-ablative and systemic therapies. In
      this review we focus on treatment options in HCC and their allocation. Although
      significant research is in progress, to this date, the results are unsatisfactory
      with limited long-term survival. In the fight against this deadly disease, there
      is still a long way to go. 

PMID- 25848481
TI  - Role of diet on non-alcoholic fatty liver disease: An updated narrative review.
AB  - The purpose of this article review is to update what is known about the role of
      diet on non-alcoholic fatty liver disease (NAFLD). NAFLD is the most common cause
      of chronic liver disease in the developed world and is considered to be a
      spectrum, ranging from fatty infiltration of the liver alone (steatosis), which
      may lead to fatty infiltration with inflammation known as non alcoholic
      steatohepatitis While the majority of individuals with risk factors like obesity
      and insulin resistance have steatosis, only few people may develop
      steatohepatitis. Current treatment relies on weight loss and exercise, although
      various insulin-sensitizing medications appear promising. Weight loss alone by
      dietary changes has been shown to lead to histological improvement in fatty liver
      making nutrition therapy to become a cornerstone of treatment for NAFLD.
      Supplementation of vitamin E, C and omega 3 fatty acids are under consideration
      with some conflicting data. Moreover, research has been showed that saturated
      fat, trans-fatty acid, carbohydrate, and simple sugars (fructose and sucrose) may
      play significant role in the intrahepatic fat accumulation. However, true
      associations with specific nutrients yet to be clarified. 

PMID- 25848482
TI  - Variations and mutations in the hepatitis B virus genome and their associations
      with clinical characteristics.
AB  - Hepatitis B virus (HBV) infection is major global issue, because chronic HBV
      infection is strongly associated with liver cancer. HBV spread worldwide with
      various mutations and variations. This variability, called quasispecies, is
      derived from no proof-reading capacity of viral reverse transcriptase. So far,
      thousands of studies reported that the variety of genome is closely related to
      the geographic distribution and clinical characteristics. Recent technological
      advances including capillary sequencer and next generation sequencer have made in
      easier to analyze mutations. The variety of HBV genome is related to not only
      antigenicity of HBs-antigen but also resistance to antiviral therapies.
      Understanding of these variations is important for the development of diagnostic
      tools and the appropriate therapy for chronic hepatitis B. In this review, recent
      publications in relation to HBV mutations and variations are updated and
      summarized. 

PMID- 25848483
TI  - Prevention of hepatocellular carcinoma: Focusing on antioxidant therapy.
AB  - Oxidative stress has been investigated in the context of alcoholic liver injury
      for many years and shown to be a causal factor of chronic hepatitis C (CHC),
      nonalcoholic steatohepatitis (NASH), drug-induced liver injury, Wilson's disease,
      and hemochromatosis. In CHC, it has been demonstrated that oxidative stress plays
      an important role in hepatocarcinogenesis. In cases with persistent hepatitis due
      to failure of hepatitis C virus eradication, or chronic liver disease, such as
      NASH, the treatment of which remains unestablished, it is important to reduce
      serum alanine aminotransferase levels and prevent liver fibrosis and development
      of hepatocellular carcinoma. This also suggests the importance of antioxidant
      therapy. Among treatment options where it would be expected that anti
      inflammatory activity plays a role in their confirmed efficacy for chronic
      hepatitis, iron depletion therapy, glycyrrhizin, ursodeoxycholic acid, Sho-Saiko
      To, and vitamin E can all be considered antioxidant therapies. To date, however,
      the ability of these treatments to prevent cancer has been confirmed only in CHC.
      Nevertheless, anti-inflammatory and anti-fibrotic effects have been demonstrated
      in other liver diseases and these therapies may potentially be effective for
      cancer prevention. 

PMID- 25848484
TI  - Occult hepatitis B virus infection and blood transfusion.
AB  - Transfusion-transmitted infections including hepatitis B virus (HBV) have been a
      major concern in transfusion medicine. Implementation of HBV nucleic acid testing
      (NAT) has revealed occult HBV infection (OBI) in blood donors. In the mid-1980s,
      hepatitis B core antibody (HBc) testing was introduced to screen blood donors in
      HBV non-endemic countries to prevent transmission of non-A and non-B hepatitis.
      That test remains in use for preventing of potential transmission of HBV from
      hepatitis B surface antigen (HBsAg)-negative blood donors, even though anti
      hepatitis C virus tests have been introduced. Studies of anti-HBc-positive donors
      have revealed an HBV DNA positivity rate of 0%-15%. As of 2012, 30 countries have
      implemented HBV NAT. The prevalence of OBI in blood donors was estimated to be
      8.55 per 1 million donations, according to a 2008 international survey. OBI is
      transmissible by blood transfusion. The clinical outcome of occult HBV
      transmission primarily depends on recipient immune status and the number of HBV
      DNA copies present in the blood products. The presence of donor anti-HBs reduces
      the risk of HBV infection by approximately five-fold. The risk of HBV
      transmission may be lower in endemic areas than in non-endemic areas, because
      most recipients have already been exposed to HBV. Blood safety for HBV, including
      OBI, has substantially improved, but the possibility for OBI transmission
      remains. 

PMID- 25848487
TI  - Survival rates according to barcelona clinic liver cancer sub-staging system
      after transarterial embolization for intermediate hepatocellular carcinoma.
AB  - AIM: To investigate the survival rates after transarterial embolization (TAE).
      METHODS: One hundred third six hepatocellular carcinoma (HCC) patients [90
      barcelona clinic liver cancer (BCLC) B] were submitted to TAE between August 2008
      and December 2013 in a single center were retrospectively studied. TAE was
      performed via superselective catheterization followed by embolization with
      polyvinyl alcohol or microspheres. The date of the first embolization until death
      or the last follow-up date was used for the assessment of survival. The survival
      rates were calculated using the Kaplan-Meier method, and the groups were compared
      using the log-rank test. RESULTS: The overall mean survival was 35.8 mo (95%CI:
      25.1-52.0). The survival rates of the BCLC A patients (33.7%) were 98.9%, 79.0%
      and 58.0% at 12, 24 and 36 mo, respectively, and the mean survival was 38.1 mo
      (95%CI: 27.5-52.0). The survival rates of the BCLC B patients (66.2%) were 89.0%,
      69.0% and 49.5% at 12, 24 and 36 mo, respectively, and the mean survival was 29.0
      mo (95%CI: 17.2-34). The survival rates according to the BCLC B sub-staging
      showed significant differences between the groups, with mean survival rates in
      the B1, B2, B3 and B4 groups of 33.5 mo (95%CI: 32.8-34.3), 28.6 mo (95%CI: 27.5
      29.8), 19.0 mo (95%CI: 17.2-20.9) and 13 mo, respectively (P = 0.013).
      CONCLUSION: The BCLC sub-staging system could add additional prognosis
      information for post-embolization survival rates in HCC patients.

PMID- 25848485
TI  - Staging of liver fibrosis or cirrhosis: The role of hepatic venous pressure
      gradient measurement.
AB  - Liver fibrosis is a common histological change of chronic liver injury and it is
      closely related with portal hypertension which is hemodynamic complication of
      chronic liver disease. Currently, liver fibrosis has been known as a reversible
      dynamic process in previous literatures. Although liver biopsy is a gold standard
      for assessing the stage of liver fibrosis, it may not completely represent the
      stage of liver fibrosis because of sampling error or semi-quantative measurement.
      Recent evidences suggested that histologic, clinical, hemodynamic, and biologic
      features are closely associated in patients with chronic liver disease. Hepatic
      venous pressure gradient (HVPG) measurement has been known as a modality to
      evaluate the portal pressure. The HVPG measurement has been used clinically for
      fibrosis diagnosis, risk stratification, preoperative screening for liver
      resection, monitoring the efficacy of medical treatments, and assessing the
      prognosis of liver fibrosis. Therefore, the HVPG measurement can be used to
      monitor areas the chronic liver disease but also other important areas of chronic
      liver disease. 

PMID- 25848488
TI  - Unusual presentation of severely disseminated and rapidly progressive hydatic
      cyst: Malignant hydatidosis.
AB  - The infection caused by the tapeworm Echinococcus granulosus leads to the
      development of hydatic disease. It is the most frequent mediterranean parasitic
      infection that commonly affects the liver and rarely involves multiple organs.
      Herein, we report an exceptional and confusing presentation of hepatopulmonary
      and splenic hydatidosis due to Echinococcus granulosus that caused diagnostic
      problems occuring in a 70-year-old man, treated with chemotherapy, with favorable
      outcome. This was a very unusual case of disseminated hydatid cyst highlighting
      the interest of keeping a high level of clinical suspicion of this diagnosis
      every time we have a cystic lesion of the liver. 

PMID- 25848486
TI  - Evidence-based consensus on the diagnosis, prevention and management of hepatitis
      C virus disease.
AB  - Hepatitis C virus (HCV) is a potent human pathogen and is one of the main causes
      of chronic hepatitis round the world. The present review describes the evidence
      based consensus on the diagnosis, prevention and management of HCV disease.
      Various techniques, for the detection of anti-HCV immunoglobulin G immunoassays,
      detection of HCV RNA by identifying virus-specific molecules nucleic acid
      testings, recognition of core antigen for diagnosis of HCV, quantitative antigen
      assay, have been used to detect HCV RNA and core antigen. Advanced technologies
      such as nanoparticle-based diagnostic assays, loop-mediated isothermal
      amplification and aptamers and Ortho trak-C assay have also come to the front
      that provides best detection results with greater ease and specificity for
      detection of HCV. It is of immense importance to prevent this infection
      especially among the sexual partners, injecting drug users, mother-to-infant
      transmission of HCV, household contact, healthcare workers and people who get
      tattoos and piercing on their skin. Management of this infection is intended to
      eradicate it out of the body of patients. Management includes examining the
      treatment (efficacy and protection), assessment of hepatic condition before
      commencing therapy, controlling the parameters upon which dual and triple
      therapies work, monitoring the body after treatment and adjusting the co-factors.
      Examining the treatment in some special groups of people (HIV/HCV co-infected,
      hemodialysis patients, renal transplanted patients). 

PMID- 25848489
TI  - Colorectal cancer risk in hamartomatous polyposis syndromes.
AB  - Colorectal cancer (CRC) is a major cause of morbidity and mortality around the
      world, and approximately 5% of them develop in a context of inherited mutations
      leading to some form of familial colon cancer syndromes. Recognition and
      characterization of these patients have contributed to elucidate the genetic
      basis of CRC. Polyposis Syndromes may be categorized by the predominant
      histological structure found within the polyps. The aim of the present paper is
      to review the most important clinical features of the Hamartomatous Polyposis
      Syndromes, a rare group of genetic disorders formed by the peutz-Jeghers
      syndrome, juvenil polyposis syndrome and PTEN Hamartoma Tumor Syndrome (Bannayan
      Riley-Ruvalacaba and Cowden Syndromes). A literature search was performed in
      order to retrieve the most recent and important papers (articles, reviews,
      clinical cases and clinical guidelines) regarding the studied subject. We
      searched for terms such as "hamartomatous polyposis syndromes", "Peutz-Jeghers
      syndrome", "juvenile polyposis syndrome", "juvenile polyp", and "PTEN hamartoma
      tumour syndrome" (Cowden syndrome, Bananyan-Riley-Ruvalcaba). The present article
      reports the wide spectrum of disease severity and extraintestinal manifestations,
      with a special focus on their potential to develop colorectal and other
      neoplasia. In the literature, the reported colorectal cancer risk for Juvenile
      Polyposis, Peutz-Jeghers and PTEN Hamartoma Tumor Syndromes are 39%-68%, 39%-57%
      and 18%, respectively. A review regarding cancer surveillance recommendations is
      also presented. 

PMID- 25848490
TI  - Long-term survival following radiofrequency ablation of colorectal liver
      metastases: A retrospective study.
AB  - AIM: To retrospectively evaluate the long-term survival of patients that received
      radiofrequency ablation (RFA) therapies of colorectal liver metastases. METHODS:
      In 2005 to 2008, RFA of 105 colorectal liver metastases (CRLM) were performed on
      49 patients in our institution. The liver metastases were evaluated, both before
      and after ablation therapies, with contrast enhanced computerised tomography and
      contrast enhanced ultrasonography. Histological evidence of malignant liver
      metastases was obtained in the few instances where contrast enhanced
      ultrasonography gave equivocal results. Accesses to the CRLM were guided
      ultrasonically in all patients. The data obtained from records of these ablations
      were retrospectively analysed and survival data were compared with existing
      studies in the literature. RESULTS: 1-, 2-, 3-, 4- and 5-year survival rates,
      when no stringent selection criteria were applied, were 92%, 65%, 51%, 41% and
      29% respectively. To explore the impact of the number and size of CRLM on
      patients' survival, an exclusion of 13 patients (26.5%) with number of CRLM >= 5
      and tumour size >= 40 mm resulted in 1-, 2-, 3-, 4- and 5-year survival rates
      improving to 94%, 69%, 53%, 42% and 31% respectively. It is of note that 9 of 49
      patients developed extra-hepatic metastases, not visible or seen on pre-treatment
      scans, just after RFA treatment. These patients had poorer survival. The
      development of extra-hepatic metastases in nearly 20% of the patients included in
      our study can partly account for modestly lower survival rates as compared with
      earlier studies in the literature. CONCLUSION: Our study underscores the fact
      that optimum patients' selection before embarking on RFA treatment is vitally
      important to achieving a superior outcome.

PMID- 25848491
TI  - Respiratory distress due to malignant ascites palliated by hyperthermic
      intraperitoneal chemotherapy.
AB  - Malignant ascites is a common symptom in patients with peritoneal cancer. Current
      assumption is that an increased vascular permeability and obstruction of
      lymphatic channels lead to the accumulation of fluid in the abdominal cavity.
      This case report describes a severely symptomatic patient with malignant ascites.
      The previously healthy 73-year-old male was presented with abdominal distention
      causing respiratory distress. Computed tomography revealed large amounts of
      ascites, a recto-sigmoidal mass with locoregional lymphadenopathy and an omental
      cake. Biopsy taken during colonoscopy revealed an adenocarcinoma of the colon
      with signet cell differentiation. A widespread peritoneal carcinomatosis was
      found during a diagnostic laparoscopy. The extent of peritoneal disease rendered
      the patient not suitable for cytoreductive surgery with curative intent. The
      ascites proved to be refractory to ultrasound-guided paracentesis; thus, a
      decision was made to perform palliative hyperthermic intraperitoneal chemotherapy
      without cytoreductive surgery. Consequently, ascites production stopped, and the
      respiratory distress was relieved thereafter. The postoperative recovery was
      uneventful. Ascites recurred eight months later, and a second hyperthermic
      intraperitoneal chemotherapy procedure was performed. The patient was still alive
      at the time of writing, 16 mo after the initial diagnosis. 

PMID- 25848492
TI  - Successful emergency resection of a massive intra-abdominal hemophilic
      pseudotumor.
AB  - An intra-abdominal pseudotumor is a rare complication of hemophilia. Surgical
      treatment is associated with high morbidity and mortality rates and reported
      cases are scarce. We present a 66-year-old Caucasian male suffering from severe
      hemophilia type A treated for 10 years with Factor VIII. Major complications from
      the disease were chronic hepatitis B and C, cerebral hemorrhage and disabling
      arthropathy. Twenty-three years ago, retro-peritoneal bleeding led to the
      development of a large intra-abdominal pseudotumor, which was followed-up
      clinically due to the high surgical risk and the lack of clinical indication. The
      patient presented to the emergency department with severe sepsis and umbilical
      discharge that had appeared over the past two days. Abdominal computed tomography
      images were highly suggestive of a bowel fistula. The patient was taken to the
      operating room under continuous infusion of factor VIII. Surgical exploration
      revealed a large infected pseudotumor with severe intra-abdominal adhesions and a
      left colonic fistula. The pseudotumor was partially resected en bloc with the
      left colon leaving the posterior wall intact. The postoperative period was
      complicated by septic shock and a small bowel fistula that required reoperation.
      He was discharged on the 73(rd) hospital day and is well 8 mo after surgery. No
      bleeding complications were encountered and we consider surgery safe under factor
      VIII replacement therapy. 

PMID- 25848493
TI  - Incarcerated amyand hernia.
AB  - Amyand's hernia is a rare condition defined by the inclusion of the appendix
      vermiformis within the hernia sac. Its incidence among cases of groin hernia is
      less than 1%. The clinical manifestation of incarcerated inguinal hernia
      generally masks the symptoms and signs of acute appendicitis, which renders
      preoperative diagnosis difficult. In this study, we present two cases of Amyand's
      hernia that were diagnosed preoperatively. The patients were taken for operation
      with the prediagnosis of incarcerated inguinal hernia. We evaluated these cases
      along with data from prior studies. 

PMID- 25848494
TI  - Communication of brain network core connections altered in behavioral variant
      frontotemporal dementia but possibly preserved in early-onset Alzheimer's
      disease.
AB  - Diffusion imaging and brain connectivity analyses can assess white matter
      deterioration in the brain, revealing the underlying patterns of how brain
      structure declines. Fiber tractography methods can infer neural pathways and
      connectivity patterns, yielding sensitive mathematical metrics of network
      integrity. Here, we analyzed 1.5-Tesla whole-brain diffusion-weighted images from
      64 participants - 15 patients with behavioral variant frontotemporal dementia
      (bvFTD), 19 with early-onset Alzheimer's disease (EOAD), and 30 healthy elderly
      controls. Using whole-brain tractography, we reconstructed structural brain
      connectivity networks to map connections between cortical regions. We evaluated
      the brain's networks focusing on the most highly central and connected regions,
      also known as hubs, in each diagnostic group - specifically the "high-cost"
      structural backbone used in global and regional communication. The high-cost
      backbone of the brain, predicted by fiber density and minimally short pathways
      between brain regions, accounted for 81-92% of the overall brain communication
      metric in all diagnostic groups. Furthermore, we found that the set of pathways
      interconnecting high-cost and high-capacity regions of the brain's communication
      network are globally and regionally altered in bvFTD, compared to healthy
      participants; however, the overall organization of the high-cost and high
      capacity networks were relatively preserved in EOAD participants, relative to
      controls. Disruption of the major central hubs that transfer information between
      brain regions may impair neural communication and functional integrity in
      characteristic ways typical of each subtype of dementia.

PMID- 25848495
TI  - Enhanced semiempirical QM methods for biomolecular interactions.
AB  - Recent successes and failures of the application of 'enhanced' semiempirical QM
      (SQM) methods are reviewed in the light of the benefits and backdraws of adding
      dispersion (D) and hydrogen-bond (H) correction terms. We find that the accuracy
      of SQM-DH methods for non-covalent interactions is very often reported to be
      comparable to dispersion-corrected density functional theory (DFT-D), while
      computation times are about three orders of magnitude lower. SQM-DH methods thus
      open up a possibility to simulate realistically large model systems for problems
      both in life and materials science with comparably high accuracy. 

PMID- 25848496
TI  - Role of P2X7 and P2Y2 receptors on alpha-secretase-dependent APP processing:
      Control of amyloid plaques formation "in vivo" by P2X7 receptor.
AB  - Amyloid precursor protein (APP) is expressed in a large variety of neural and non
      neural cells. The balance between non-pathogenic and pathologic forms of APP
      processing, mediated by alpha-secretase and beta-secretase respectively, remains
      a crucial step to understand beta-amyloid, Abeta42 peptide, formation and
      aggregation that are at the origin of the senile plaques in the brain, a
      characteristic hallmark of Alzheimer's disease (AD). In Neuro-2a, a neuroblastoma
      cell line that constitutively expresses APP, activation of the P2X7 receptor
      leads to reduction of alpha-secretase activity, the opposite effect being
      obtained by P2Y2 receptor activation. The in vivo approach was made possible by
      the use of J20 mice, a transgenic mouse model of familial Alzheimer's disease
      (FAD) expressing human APP mutant protein. This animal exhibits prominent amyloid
      plaques by six months of age. In vivo inhibition of the P2X7 receptor induced a
      significant decrease in the number and size of hippocampal amyloid plaques. This
      reduction is mediated by an increase in the proteolytic processing of APP through
      alpha-secretase activity, which correlates with an increase in the phosphorylated
      form of GSK-3, a less active form of this enzyme. The in vivo findings
      corroborate the therapeutic potential of P2X7 antagonists in the treatment of
      FAD. 

PMID- 25848498
TI  - Genotyping of carbapenem resistant Acinetobacter baumannii isolated from tracheal
      tube discharge of hospitalized patients in intensive care units, Ahvaz, Iran.
AB  - BACKGROUND AND OBJECTIVES: Carbapenem resistant A. baumannii is an emerging cause
      of nosocomial infections. The aims of this study were identification of the most
      prevalent of carbapenem resistant genes, molecular typing and antimicrobial
      evaluation of A.baumannii in intensive care units. MATERIALS AND METHODS: Two
      hundred and six A. baumannii were isolated from tracheal tube discharge of
      hospitalized patients at different intensive care units in Ahvaz, Iran.
      Antimicrobial susceptibility test was done on all isolates. Multiplex and
      singleplex PCR were performed for detection of bla OXA-23-like, bla OXA-24-like,
      bla OXA-51-like, bla OXA-58-like, bla VIM, bla IMP, bla SPM and bla NDM genes.
      Genetic relationship of all isolates was determined by REP-PCR method. RESULTS:
      Out of 206 examined isolates, 198 (96.1%) isolates were resistant to imipenem and
      meropenem. However 3.9% isolates were sensitive to these antibiotics. The bla OXA
      23-like and bla OXA-24-like genes were detected in 85% and 8.7% of strains,
      respectively. No bla OXA-58- like, bla IMP, bla VIM, bla SPM and bla NDM were
      detected. REP-PCR results showed that isolates were belonged to five genotypes:
      Genotype A was the most prevalent (P- value < 0.001): it was observed in 75 of
      206 strains (36.4%). Genotype B, and C were found in 28.6% and 27.7%,
      respectively. The rate of other genotypes was as follows: D (2.4%), E (1%).
      CONCLUSION: Based on the obtained results, the rate of carbapenem resistance was
      high among of A. baumannii which was isolated from intensive care units patients
      and oxacillinase genes were the most prevalent carbapenem resistant genes. These
      results revealed that three clones, A, B and C of A.baumannii are common in our
      hospitals.

PMID- 25848499
TI  - Multidrug resistant Gram-negative bacilli in lower respiratory tract infections.
AB  - BACKGROUND: Lower respiratory tract infections are among important causes of
      morbidity and mortality for all age groups. The emergence of multidrug resistant
      Gram-negative bacilli is an issue of increasing concern. MATERIALS AND METHODS: A
      retrospective study including respiratory specimens (sputum and BAL) was
      conducted in our tertiary care centre. Samples were processed for microscopy,
      culture and susceptibility testing following standard methods. Multidrug
      resistant Gram-negative bacilli causing lower respiratory tract infections were
      studied for their causation of disease. The effect of appropriate treatment on
      clinical outcome was observed. RESULTS: A total of 472 Gram-negative pathogens
      were isolated from sputum and broncho-alveolar lavage fluid specimens during the
      study period. Among these Gram-negative pathogens 175 (37%) were found to be
      multidrug resistant. Klebsiella pneumoniae 85 (48.6%) and Acinetobacter spp. 59
      (33.7%) were the predominant multidrug resistant Gram-negative bacilli isolated.
      Based on clinico-microbiological correlation, 138 (78.9%) multidrug resistant
      isolates were found to be pathogenic and the rest 37 (21.1%) were considered as
      colonizers. After initiating appropriate antibiotic therapy, clinical improvement
      was seen in 110 (79.7%) patients. In the patients who showed improvement,
      amikacin (34.3%) and cefoperazone-sulbactum (21.8%) were found to be the most
      effective drugs. CONCLUSION: A large majority of the isolated multidrug resistant
      Gram-negative bacilli were found to be pathogenic. Regular surveillance which
      directs appropriate empirical therapy; and good clinic-microbiological workup of
      each case of lower respiratory tract infection can reduce the morbidity and
      mortality associated with multidrug resistant organisms.

PMID- 25848497
TI  - Biochemical functional predictions for protein structures of unknown or uncertain
      function.
AB  - With the exponential growth in the determination of protein sequences and
      structures via genome sequencing and structural genomics efforts, there is a
      growing need for reliable computational methods to determine the biochemical
      function of these proteins. This paper reviews the efforts to address the
      challenge of annotating the function at the molecular level of uncharacterized
      proteins. While sequence- and three-dimensional-structure-based methods for
      protein function prediction have been reviewed previously, the recent trends in
      local structure-based methods have received less attention. These local structure
      based methods are the primary focus of this review. Computational methods have
      been developed to predict the residues important for catalysis and the local
      spatial arrangements of these residues can be used to identify protein function.
      In addition, the combination of different types of methods can help obtain more
      information and better predictions of function for proteins of unknown function.
      Global initiatives, including the Enzyme Function Initiative (EFI), COMputational
      BRidges to EXperiments (COMBREX), and the Critical Assessment of Function
      Annotation (CAFA), are evaluating and testing the different approaches to
      predicting the function of proteins of unknown function. These initiatives and
      global collaborations will increase the capability and reliability of methods to
      predict biochemical function computationally and will add substantial value to
      the current volume of structural genomics data by reducing the number of absent
      or inaccurate functional annotations. 

PMID- 25848500
TI  - Molecular evaluations of extended spectrum beta-lactamase producing strains of
      Serratia isolated from blood samples of the patients in Namazi Hospital, Shiraz,
      Southern Iran.
AB  - BACKGROUND AND OBJECTIVE: Nowadays, the presence of extended-spectrum beta
      lactamases (ESBLs) producing strains in Serratia genus causes the emergence of
      resistance to many antibiotics. So, the lack of proper diagnosis of ESBLs strains
      can lead to failure in the treatment. The objective of the present study was to
      investigate ESBLs production in Serratia strains isolated from the clinical blood
      samples in Shiraz, Iran. MATERIALS AND METHODS: In this study, 39 Serratia
      strains isolated from the patients referred to Namazi Hospital, during a 2 year
      period were tested. The antimicrobial resistance of the isolates to 21
      antibiotics was evaluated using Kirby-Bauer disk diffusion method. Combination
      disk method was used to determine the ESBL phenotype among the isolates. PCR was
      performed to investigate the presence of ESBL genes of SHV, OXA and TEM types.
      RESULTS: The lowest antibiotic resistance rates belonged to meropenem (7.69%) and
      imipenem (5.12%). Overall, positive ESBL phenotype was identified in 69% (n = 27)
      of the isolates, 70.37% (n = 19) for S. marcescens and 29.62% (n = 8) for S.
      liquefaciens. Results obtained by PCR showed that only 20.51% carried OXA gene
      and 15.38% carried SHV-1 gene. TEM gene was detected in none of the isolates.
      CONCLUSION: This study showed a high prevalence of the emerging ESBL producing
      strains among clinical isolates of Serratia that could lead to an increase in
      antibiotic resistance. However, ESBLs genes other than those tested here may be
      more responsible for the emergence of ESBL phenotype among Serratia clinical
      isolates in our region.

PMID- 25848501
TI  - Magnitude of drug resistant shigellosis in Nepalese patients.
AB  - BACKGROUND AND OBJECTIVES: Shigella plays an important role as a causative
      organism of acute gastroenteritis, in children and others. Rapid emergence of
      antibiotic resistance warrants continuous monitoring of susceptibility pattern of
      bacterial isolates. We report here our findings about Shigella spp. isolates and
      their drug resistance patterns in Nepalese patients. MATERIALS AND METHODS: The
      study was conducted on 507 Nepalese patients with acute gastroenteritis attending
      outpatient and inpatient departments of Nepalgunj Medical college and teaching
      Hospital, Banke, Nepal from September 2011 to April 2013. Stool specimens were
      processed for isolation and identification of Shigella species following the
      standard microbiological methods while the disc diffusion test was used to
      determine antimicrobial resistance patterns of the recovered isolates at the
      central Laboratory of Microbiology. RESULTS: Sixty nine isolates were identified
      as Shigella species. S. flexneri, S. dysenteriae, S. boydii and S. sonnei
      accounted, respectively, for 42.03%, 27.54%, 21.74% and 8.70% of the total number
      of Shigella isolates. Resistance to nalidixic acid (95.65%), ampicillin (85.51%),
      co-trimoxazole (82.61%) and ciprofloxacin (47.83%) was observed. Among 69
      isolates, 29 (42.03%) were from children aged 1-10 years and this group was
      statistically significant (P < 0.05), compared to the other age groups.
      CONCLUSIONS: The study revealed endemicity of shigellosis with S. flexneri as the
      predominant serogroup in Nepalese patients. Children were at a higher risk of
      severe shigellosis. Nalidixic acid, ampicillin, co-trimoxazole and ciprofloxacin
      should not be used empirically as the first line drugs in treatment of
      shigellosis. Continuous local monitoring of resistance patterns is necessary for
      the appropriate selection of empirical antimicrobial therapy.

PMID- 25848502
TI  - Conventional and molecular investigation of Shigella isolates in relation to an
      outbreak in the area of Isfahan, Iran.
AB  - BACKGROUND AND OBJECTIVE: Over 165 million cases of shigellosis occur in the
      world each year, mostly in developing countries. Outbreaks of shigellosis are
      associated with poor sanitation, natural calamities, contaminated food and
      crowded living conditions. In late summer 2006, during the final stage of an
      outbreak of shigellosis at a vast region of Isfahan province, Naein & Ardestan,
      our laboratory was assigned to investigate the outbreak in order to determine the
      causative agent. MATERIALS AND METHODS: A total of 146 rectal swabs which had
      been collected from the patients by local laboratories on separate days were
      screened using a battery of conventional and molecular tests. RESULTS: Thirteen
      specimens tested positive for Shigella spp. They were identified as S. sonnei (6,
      46.1%), S. dysenteriae (4, 30.8%), S. flexneri (2, 15.4%) and Shigella spp (1,
      7.7%) by conventional and molecular microbiological tests. According to
      ribotyping results the isolates were grouped into 3 distinct clusters
      encompassing the majority of isolates and a single line of descent representing
      isolate S122 which was nonreactive with any Shigella polyvalent antisera.
      CONCLUSION: This diarrheal outbreak appeared to be the result of shigellosis.
      Despite the fact that Shigella sonnei was the predominant organism isolated from
      patients, the causative agent of outbreak diarrhea remains obscure, since other
      Shigella species were also involved. The serologic testing supports this
      conclusion, as do the molecular patterns of the Shigella isolates. Having
      considered the time of investigation which was in the late stage of the outbreak,
      it was very likely that a collection of endemic and epidemic clinical samples was
      screened resulting in isolation of various Shigella species.

PMID- 25848503
TI  - Genetic evaluation of Locus of enterocyte effacement pathogenicity island (LEE)
      in Enteropathogenic Escherichia coli isolates (EPEC).
AB  - BACKGROUND AND OBJECTIVES: Enteropathogenic Escherichia coli (EPEC) divided into
      two groups typical and atypical (aspect). The main virulence genes are located in
      a pathogenicity island called LEE (Locus of Enterocyte Effacement). LEE
      frequently inserted in tRNA genes of selC, pheU and pheV in the bacterial
      chromosome. tEPEC and aEPEC strains have some differences in their pathogenicity.
      The purpose of this was to investigate the possible differences between tEPEC and
      aEPEC strains according to the virulence genes encoding by LEE and their relation
      to insertion sites. MATERIALS AND METHODS: In this study 130 E. coli isolates
      confirmed by biochemical analysis from diarrheal patients, were evaluated for
      EPEC pathotype by PCR. All EPEC strains tested for presence of some LEE encoded
      virulence genes and sites of LEE insertion by PCR method. RESULTS: Among 50
      strains of EPEC 28 (56%) and 22 (44%) were typical and atypical strains
      respectively. 19 strains (30%) showed insertion in selC, 7 (14%) in pheU, 4 (8%)
      in pheV, 8 (16%) in pheU and pheV, 1 (2%) in selC and pheU, 6 (12%) in pheV, pheU
      and selC and 5 (10%) had no insertion in these sites. Moreover, spa (n = 8, 16%),
      espB (n = 16, 32%), espD (n = 18, 36%), espF (n = 8, 16%), espG (n = 13, 26%),
      espH (n = 12, 24%), map (n = 11, 32%) and tir (n = 4, 8%) were present among the
      strains. CONCLUSION: Results showed that most of the virulence genes are present
      in tEPEC isolates. However, aEPEC isolates may acquire other virulence factors.
      The majority of tEPEC strains showed insertion at selC and aEPEC strains in pheV
      and pheU.

PMID- 25848504
TI  - Construction of a Baculovirus vector containing A subunit of Shiga toxin for
      protein delivery.
AB  - BACKGROUND AND OBJECTIVES: Baculovirus can be used as a vector in gene delivery
      system. Viral envelope of baculovirus would display expressed protein/peptide and
      it could render as a potential vaccine delivery system. In this regard, the gene
      coding for A subunit of shiga toxin (StxA) from Escherichia coli (E. coli) strain
      was cloned in a baculovirus expression system. StxA subunit has the ability to
      inhibit protein synthesis and this ability applied in cancer therapy. In this
      study, expression of StxA in baculovirus as a protein delivery system was
      assessed in vitro. MATERIAL AND METHODS: StxA gene was cloned in pTriExTM
      multisystem expression vector. This vector enables the protein expression in
      multisystem, E. coli and baculovirus. This construct was used to express the gene
      in E. coli and baculovirus. The construct containing StxA gene was made in
      baculovirus and expression was confirmed, then baculovirus expressing STXA
      transfect HeLa cells. RESULTS: The expression of STXA peptide (32kDa) was
      confirmed by SDS-PAGE and western blotting in both expression systems. The A
      subunit challenge to human cell Lines was applied as a delivery system by
      baculoviruses. On the other hand, the inhibition of cell proliferation was also
      demonstrated by baculovirus containing STXA subunit. CONCLUSION: STXA peptide
      expression in baculovirus was shown in E. coli and baculovirus expression system.
      Furthermore, it was shown that A subunit of Shiga toxin delivered by baculovirus
      can inhibit cell proliferation in HeLa cells and leading to cell death.
      Therefore, this prototype system could be a promising model for in vivo cancer
      therapy and targeted protein delivery system.

PMID- 25848505
TI  - Screening of soil actinomyectes against Salmonella serovar Typhi NCTC 5761 and
      characterization of the prominent active strains.
AB  - BACKGROUND AND OBJECTIVES: Annual incidence of infection with S. Typhi is
      estimated to be about 17 million cases worldwide. A systematic search among
      actinomycete isolates from soil of Iran aimed at finding active actinomycetes
      against the causative agent of typhoid fever, Salmonella Typhi was carried out
      during this study. MATERIALS AND METHODS: Our anti-Salmonella screening program
      resulted in nine highly active actinomycete isolates. All nine antibiotic
      producing strains showed broad-spectrum antibacterial activity, as five strains
      showed antifungal activity as well. Based on microscopic morphology and cell wall
      analysis, all nine active actinomycete strains were representatives of the genus
      Streptomyces. Three of the producing strains including the isolates HG87, HG116
      and HG443 with inhibition zone of >20 mm, were selected for further
      identification and investigation of cytotoxic effects. RESULTS AND CONCLUSION:
      None of the producing strains showed cytotoxicity on HEK and USSC cell lines,
      while strain HG116 showed excellent antitumor activity on T47D cancer cell lines.
      Isolates HG87, HG116 and HG443 can be distinguished from the related species by
      some phenotypic and biochemical characteristics. Our results demonstrate the
      broad-range biological activity exhibited by bioactive compounds of soil
      actinomycetes from Iran.

PMID- 25848507
TI  - Cloning, expression and purification of Mycobacterium tuberculosis ESAT-6 and CFP
      10 antigens.
AB  - BACKGROUND AND OBJECTIVES: ESAT-6 (6-kDaearly secretory antigenic target) and CFP
      10 (10-kDa culture filtrate protein) have been described as dominant antigens
      recognized by T-cells and considered as virulence factors in Mycobacterium
      tuberculosis. The aim of this study was to clone, express and purify recombinant
      ESAT-6 andCFP-10 proteins of M. tuberculosis in soluble form. MATERIALS AND
      METHODS: ESAT-6 andCFP-10 genes were amplified by PCR, cloned into pET32a (+)
      vector, and overexpress-ed using isopropyl-beta-D-thiogalactopyranoside in E.
      coli BL21 (DE3). ESAT-6 andCFP-10 proteins were purified by Ni-NTA affinity
      chromatography and were detected by anti- ESAT-6 and anti -CFP-10 antibodies.
      RESULTS: ESAT-6 andCFP-10 genes were successfully expressed and purified. Anti-
      ESAT-6 and anti-CFP-10 antibodies were produced after induction of immunization
      against purified ESAT-6 andCFP-10 proteins in rabbit. CONCLUSION: In this study,
      we cloned, expressed and purified sufficient amounts of ESAT-6 andCFP-10 and it
      would be tested for the development of diagnostic kit for M. tuberculosis in
      future.

PMID- 25848506
TI  - Molecular diversity of Mycobacterium tuberculosis strains indifferent provinces
      of Iran.
AB  - BACKGROUND AND OBJECTIVES: Molecular epidemiology tools are widely used in
      determining epidemiology of tuberculosis. Spoligotyping is a molecular
      epidemiology method that is used for characterization and typing of Mycobacterium
      tuberculosis complex strains. The method is based on polymorphism of the
      chromosomal DR locus consisting of identical 36-bp DRs alternating with 35-41
      unique spacers. The objective of this study was to investigate the prevalence of
      M. tuberculosis spoligotypes in different provinces of Iran. MATERIALS AND
      METHODS: M. tuberculosis strains were isolated from TB patients of
      Mycobacteriology Research center (MRC). DNA was extracted from patient's clinical
      samples. PCR was performed by using of specific primers for DR region. The
      amplified DNA was hybridized to the spoligotyping Membrane. Hybridized DNA was
      detected with ECL detection kit and by exposing ECL Hyperfilm to the membrane.
      The obtained result was entered to a binary format and was analyzed using SpolDB4
      database. RESULTS: Spoligotyping resulted in 136 different patterns. Out of 1242
      M. tuberculosis strains, 1165 strains (93.8%) were classified into 59 clusters
      and the remaining strains (6.2 %) were singleton. CONCLUSIONS: The results of
      present study showed that strains of CAS family were more prevalent than other
      strains in Iran. Other prevalent families were Haarlem, T and Beijing,
      respectively.

PMID- 25848508
TI  - Comparison of four different culture media for growth of Mycobacterium avium
      subsp. avium isolated from naturally infected lofts of domestic pigeons.
AB  - BACKGROUND AND OBJECTIVES: Diagnosis of avian tuberculosis by conventional
      culture method is still considered as the "gold standard" technique. The main
      objective of this study was to compare growth of Mycobacterium avium subsp. avium
      on four specific Mycobacterial cultures such as glycerinated Lowenstein-Jensen
      medium, pyruvate-enriched Lowenstein-Jensen medium, mycobactin J-supplemented
      Herrold-egg yolk medium and plain Herrold-egg yolk medium. MATERIALS AND METHODS:
      Eighty out of more than 600 pigeons were selected based on their clinical signs
      and poor health conditions. The birds were numbered and their clinical signs were
      registered in the working sheets, and under standard condi-tion, euthanized,
      subjecting to necropsy examinations, followed by bacterial culture on four
      specific media for Mycobacterium avium subsp. avium, including glycerinated
      Lowenstein-Jensen (LJG) medium, pyruvate-enriched Lowenstein-Jensen medium (LJP),
      mycobactin J-supplemented Herrold-egg yolk medium and plain Herrold-egg yolk
      medium. RESULTS: Fifty one Mycobacterium avium subsp. avium were isolated from
      pigeons. Mycobactin J-supplemented Herrold-egg yolk media yielded greater number
      of colonies in shorter incubation time in compare with other media. CONCLUSION:
      It was concluded that most of the isolates need mycobactin as a growth factor.

PMID- 25848509
TI  - Evaluation of FLASH - PCR forrapid detection of Mycobacterium tuberculosis from
      clinical specimens.
AB  - BACKGROUND AND OBJECTIVES: Tuberculosis (TB) is the oldest known bacterial
      disease in humans. Due to the rise of morbidity in recent years, early diagnosis
      of the disease is necessary. MATERIALS AND METHODS: In this study we used
      Fluorescent Amplification-Based Specific Hybridization (FLASH) PCR to
      targetIS6110 for rapid detection of M. tuberculosis (MTB). To investigate the
      important factors influencing the risk of TB, data from patients and their
      medical records were analyzed. RESULT: The sensitivity and specificity of FLASH
      PCR for detecting MTB were determined as 93.33% and 92.5%, respectively. The
      findings of this study have suggested that removal of the contaminants in FLASH
      PCR sign ificantly reduced the detection time, and MTB was much more rapidly
      detected in the clinical specimens compared to the conventional culture and smear
      examination. Results of the medical survey showed that the majority of TB
      patients were males, over 51 years old, smokers, with pulmonary TB and normal
      chest X-ray (CXR). CONCLUSION: MTB can be rapidly detected inclinical specimens
      using FLASH-PCR in comparison with culture and smear examination.

PMID- 25848510
TI  - Microbiological tests to identify a link between periodontitis and acute
      myocardial infarction-an original research.
AB  - BACKGROUND AND OBJECTIVES: Gingival and periodontal diseases are associated with
      specific bacterial infections. The main aim of the study was to know whether the
      periodontitis is associated with an increased risk for acute myocardial
      infarction (AMI) and to know the distribution of Porphyromonas gingivalis in
      patients with acute myocardial infarction associated with chronic periodontitis
      and acute myocardial infarction Groups. MATERIALS AND METHODS: Out of 50
      patients, 20 were diagnosed as acute myocardial infarction associated with
      chronic periodontitis (Group I), twenty patients were suffering from AMI (Group
      II) and 10 patients were healthy (control Group III). RESULTS AND CONCLUSION:
      Periodontal pathogens were identified by phenotypic, enzymatic and hybridization
      methods. The total bacterial load and the number of Porphyromonas gingivalis
      pathogens were more in Group I when compared to Group II and Group III. Thus, the
      present study confirmed an association between periodontitis and AMI.

PMID- 25848512
TI  - Detection of virulence genes (bvfA, virB and ure) in Brucella melitensis isolated
      from aborted fetuses of sheep and goats.
AB  - BACKGROUND AND OBJECTIVES: Brucella, causative of brucellosis, has some potential
      virulence factors involved in Brucella replication and its strategies to
      circumvent the immune response. One of them is the virB gene that encodes the
      type IV secretion system proteins (T4SS) involved in intracellular replication of
      organism. Brucella virulence factor A (bvfA), and urease (ure) has also been
      described as being implicated in survival, and virulence in the hosts. The aim of
      this study was to investigate the B. melitensis virulence factor genes among
      Brucella isolated from aborted fetuses of sheep and goats in Fars province,
      southern Iran. MATERIALS AND METHODS: A total of 42 isolates of B. melitensis
      isolated from aborted fetuses between 2005-2011 in Fars province of Iran was used
      in this study. PCR assay was performed in order to detect the virB, bvfA, and ure
      genes using specific primers. RESULTS AND CONCLUSIONS: The frequency of bvfA,
      virB, and ure genes was 78.50%, 73.80%, and 88.09% among all isolates
      respectively. The results of the present study showed that most Brucella isolates
      from this region have virulence factors genes (virB, bvfA, ure) in their genome,
      and most B. melitensis had ure genes that has been hypothesized to play a role in
      the pathogenesis of disease.

PMID- 25848511
TI  - Comparison of five diagnostic methods for Helicobacter pylori.
AB  - BACKGROUND AND OBJECTIVES: Invasive and non-invasive techniques are used to
      diagnose H. pylori infection. Some factors influence the choice of a diagnostic
      test, such as the sensitivity and specificity of the tests, the clinical
      circumstances and the cost-effectiveness of the testing strategy. The aim of this
      study was to reveal the relationship between different H. pylori infection
      diagnosis methods, and clarify the application scope of each diagnosis method.
      MATERIALS AND METHODS: patients were included in the study, and specimens
      including biopsies, blood and stool were taken. Biopsies were evaluated by
      hematoxylin and eosin, and Giemsa staining. A sequence of 294 bp in the ureC
      (glmM) gene was amplified. The rapid urease test (RUT) was performed using a non
      commercial validated test. Stool samples were analyzed using a polyclonal ELISA
      stool antigen test. A serological assay for IgG antibodies was performed by a
      commercial Helicobacter pylori IgG ELISA kit. RESULTS: According to the
      predefined criteria, a total of 46 (50.5%) patients tested were positive by at
      least 2 of the 3 biopsy-based methods. The best sensitivity (95.6%) belonged to
      histology and RUT. The sensitivities of other tests including PCR, serology and
      stool antigen test were 93.5%, 91.3% and 73.9%, respectively. RUT showed the best
      specificity (100%), and the specificities of the other tests, including PCR,
      stool antigen test, histology and serology, were 95.6%, 86.7%, 77.8% and 55.6%,
      respectively. CONCLUSION: In view of the better results obtained for invasive vs
      non-invasive tests, for a more accurate diagnosis, it is advisable not to solely
      rely on non-invasive methods of H. Pylori diagnosis.

PMID- 25848513
TI  - Comparison of histopathological analysis, culture and polymerase chain reaction
      assays to detect mucormycosis in biopsy and blood specimens.
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to compare direct
      microscopic examination with culture and PCR for the diagnosis of Mucorales
      infection in blood and tissue specimens. MATERIAL AND METHODS: Blood samples and
      tissue specimens were obtained from 28 patients (total 58 samples) with suspected
      invasive fungal infection and cultured on proper media. Direct smear of tissue
      samples was done with potassium hydroxide, hematoxylin and eosin, and methenamine
      silver staining. DNA extracted from blood and tissue specimens were used for semi
      nested PCR targeting 18S rDNA of Mucorales species. RESULTS: Mucormycosis was
      documented in 7/28 (25%) of tissue specimens with positive findings by direct
      smear, of which PCR and culture were positive in 6 (86%) and 5 (70%) specimens,
      respectively. The etiologic agents were Mucor spp. and Rhizopus spp. However,
      culture and PCR results for all blood specimens were negative. CONCLUSIONS: As
      the orders of Mucorales do not have well growth in culture media, PCR with tissue
      specimens is more sensitive than tissue or blood culture methods. Unfortunately,
      there is no alternative method for direct smear, which is an invasive method.
      Molecular methods may be helpful in these cases.

PMID- 25848515
TI  - The effect of ajowan (Carum copticum L.) essential oils on eukaryotic ruminal
      microorganisms of Mehraban sheep.
AB  - BACKGROUND AND OBJECTIVES: Essential oils may improve the utilization of
      nutrients by ruminal microorganisms. The aim of this study was to assess the
      effect of different doses of ajowan essential oils (AEO) on growth and fibrolytic
      activity of anaerobic fungi, and generic distribution of ciliated protozoa (in
      vitro). MATERIAL AND METHODS: Different doses of AEO (0, 150, 300, 450 and 600
      ppm) were added to experimental tubes. The effect of AEO was evaluated on growth
      and fibrolytic enzyme activity of an anaerobic fungus (Neocalimastix spp.).
      Generic distribution of ciliated protozoa were evaluated in response to different
      doses of AEO. RESULTS AND CONCLUSION: The growth of fungus (Neocalimastix spp.)
      were inhibited and activity of fibrolytic enzymes of fungus were reduced by
      adding AEO. Also, an inhibitory effect was seen in concentration of ciliated
      protozoa and some genus were completely disappeared at the doses of 300 ppm and
      higher. The doses used in this study reduced the fibrolytic activity of the
      studied rumen microorganisms which is undesirable in practical animal nutrition.
      Further research is needed to assess the effects of AEO at lower doses on these
      parameters and also proteolysis and methanogenesis.

PMID- 25848514
TI  - Colonization of Pneumocystis jirovecii in Chronic Obstructive Pulmonary Disease
      (COPD) patients and the rate of Pneumocystis pneumonia in Iranian non-HIV(+)
      immunocompromised patients.
AB  - BACKGROUND AND OBJECTIVES: With increasing rate of immunodeficiency diseases in
      the world, opportunistic micro-organism such as Pneumocystis jirovecii (P.
      jirovecii) become more important. Little information is available on prevalence
      of this life-threatening microorganism in Iran. This study was designed to
      determine the colonization and the rate of active disease caused by P. jirovecii
      in two groups of Iranian immunosuppressed patients. MATERIALS AND METHODS: Two
      hundred and fifty five pulmonary samples were collected from two groups of
      immunosuppressed patients to detect a 260bp fragment of mt LSU rRNA gene of P.
      jirovecii by nested PCR. The first group was COPD patients consumed oral, inhaled
      or injectable corticosteroid and the second group was patients with malignancies
      under chemotherapy. Both groups were referred to National Research Institute of
      Tuberculosis and Lung Disease and Imam Khomeini hospital because of pulmonary
      symptoms. All patients introduced to this project were confirmed HIV sera
      negative by ELISA and western blot test. RESULTS: The mean age of COPD patients
      was 66.5 +/- 11 (41-88) years and all of them were men. The mean age of patients
      with malignancy (PMs) was 43 +/- 11 (23-65) years and 51.6% were men. The P.
      jirovecii was colonized in 7 of 89 COPD patients (7.9%) and its DNA was isolated
      from 11 of 153 PMs (7.2%). The microorganism could cause active disease in 7 of
      67 (10.5%) PMs who suffered from pneumonia. CONCLUSION: The study showed that P.
      jirovecii was one of colonizing agents in the COPD patients, but it could cause
      active disease in PMs. Generally, the microorganism can exist in the lung of non
      HIV(+) immunosuppressed patients. Therefore, it should be considered as a
      potential infective agent in non-HIV(+) immunocompromised patients.

PMID- 25848516
TI  - Characterization of a lipase from a newly isolated Pseudomonas sp.
AB  - BACKGROUND AND OBJECTIVES: Lipases are valuable biocatalysts which are widely
      used in the detergent, food, dairy and pharmaceutical industries. The aims of the
      present study included the isolation of a lipase-producer from industrial zones
      and the partial characterization of the enzyme. MATERIALS AND METHODS: A number
      of bacteria were isolated from sites related to the oil industries. An isolate
      forming a halo zone in a selective medium (TW agar) was then selected and grown
      on a medium suitable for the production of lipase. The isolate was subsequently
      identified by the 16S rRNA sequencing method, and its enzyme activity was
      measured by a spectrophotometer using pNPP as a substrate. RESULTS: The selected
      isolate was identified by the molecular method as Pseudomonas sp. Its
      extracellular lipase activity was 41.5 +/- 1.4 U/ml, and the high affinity of
      this enzyme for the substrate was indicated by the kinetic parameters of Km and
      Vm, which were estimated by the the Lineweaver-Burk plot as 0.77 mM and 49.5
      U/ml, respectively. Activation energy of lipase calculated from the Arrhenius
      plot was found to be 20.78 kJ/mol, and a temperature coefficient (Q10) of 4.39
      indicated the high catalytic activity of the enzyme and the temperature
      dependence of the enzymatic reaction. CONCLUSION: The results demonstrated that
      the indigenous isolate could have potential applications in many relevant
      industries.

PMID- 25848517
TI  - Inhibition of aflatoxin biosynthesis in Aspergillus flavus by phenolic compounds
      extracted of Piper betle L.
AB  - BACKGROUND AND OBJECTIVES: Food contamination by aflatoxins is an important food
      safety concern for agricultural products. In order to identify and develop novel
      antifungal agents, several plant extracts and isolated compounds have been
      evaluated for their bioactivities. Anti-infectious activity of Piper betle used
      in traditional medicine of Malaysia has been reported previously. MATERIALS AND
      METHODS: Crude methanol extract from P. betel powdered leaves was partitioned
      between chloroform and water. The fractions were tested against A. flavus UPMC
      89, a strong aflatoxin producing strain. Inhibition of mycelial growth and
      aflatoxin biosynthesis were tested by disk diffusion and macrodillution
      techniques, respectively. The presence of aflatoxin was determined by thin-layer
      chromatography (TLC) and fluorescence spectroscopy techniques using AFB1
      standard. The chloroform soluble compounds were identified using HPLC-Tandem mass
      spectrometry technique. RESULTS: The results, evaluated by measuring the mycelial
      growth and quantification of aflatoxin B1(AFLB1) production in broth medium
      revealed that chloroform soluble compounds extract from P. betle dried leaves was
      able to block the aflatoxin biosynthesis pathway at concentration of 500MUg/ml
      without a significant effect on mycelium growth. In analyzing of this effective
      fractions using HPLC-MS(2) with ESI ionization technique, 11 phenolic compounds
      were identified. CONCLUSION: The results showed that the certain phenolic
      compounds are able to decline the aflatoxin production in A. flavus with no
      significant effect on the fungus mycelia growth. The result also suggested P.
      betle could be used as potential antitoxin product.

PMID- 25848518
TI  - Screening, identification and optimization of a yeast strain, Candida
      palmioleophila JKS4, capable of azo dye decolorization.
AB  - BACKGROUND AND OBJECTIVES: Synthetic dyes are recalcitrant to degradation and
      toxic to different organisms. Decolorization of textile wastewaters is one of the
      major concerns since last decades. Physical-chemical treatments are very
      expensive and frequently producing large amounts of toxic wastes. Biological
      treatments can be more convenient. In the present study, an attempt has been made
      for decolorization of azo dyes using microbial process. MATERIAL AND METHODS:
      Screening of microorganisms capable of azo dye decolorization was performed from
      activated sludge. The decolorization of various dyes (Reactive Black 5, Reactive
      Orange 16, Reactive Red 198, Direct Blue 71, Direct Yellow 12 and Direct Black
      22) was determined by measuring the absorbance of culture supernatant at their
      lambdamax. Culture supernatants were also analyzed for UV-Vis absorption between
      200-800 nm. The effect of aeration, temperature, different concentrations of
      glucose and NaCl was studied with an aim to determine the optimal conditions
      required for maximum decolorization. RESULTS: The yeast (strain JKS4) which had
      high ability to decolorize different azo dyes was isolated. Under aerobic
      condition, the yeast strain showed 85.7% of decolorization at 200 mg/l Reactive
      Black 5 (as a model azo dye), 1% (w/v) glucose concentration and 35 degrees C
      after 24 h. All the examined dyes were extensively decolorized (53.35-97.9%)
      after 24 h. With elongated incubation period, complete decolorization was
      observed in presence of all dyes. From the physiological properties and
      phylogenetic analysis based on the 26S rDNA sequences, strain JKS4 was classified
      into Candida palmioleophila. CONCLUSIONS: Because of high decolorizing activity
      against various azo dyes commonly used in the textile industries, it is proposed
      that the isolated yeast may have a practical application in the biotransformation
      of various dye effluents.

PMID- 25848519
TI  - Detection of AmpC-beta-lactamases producing isolates among carbapenem resistant
      P. aeruginosa isolated from burn patient.
AB  - BACKGROUND AND OBJECTIVES: Pseudomonas aeruginosa is responsible for devastating
      nosocomial infections among severely burn patients. Class C of cephalosporinase
      (AmpC-beta-lactamases) is important cause of multiple beta-lactam resistance in
      P. aeruginosa. The aim of this study was to detect the AmpC-beta-lactamases
      producing isolates among carbapenem resistant P. aeruginosa isolated from burn
      patient. MATERIAL AND METHODS: a total of 100 isolates of carbapenem resistant P.
      aeruginosa isolates from different burn patients were investigated. Three
      phenotypic methods were selected for identification of the AmpC-beta-lactamases
      producing isolates. RESULTS: Fifty four isolates were AmpC producer as detected
      by AmpC disk test. Seventeen isolates were identified as AmpC producer using
      combined disk method. Fifty two isolates showed a twofold or threefold dilution
      difference between the minimum inhibitory concentration of imipenem or
      ceftazidime and the minimum inhibitory concentration of imipenem or ceftazidime
      plus cloxacillin. One isolate was identified as AmpC producer using three
      methods. Three isolates produced AmpC as detected by both AmpC disk test and
      combined disk methods and 19 isolates were found as AmpC producer using both AmpC
      disk test and minimum inhibitory concentration methods. Six isolates were AmpC
      producer as shown by the MICs of both imipenem and ceftazidime. CONCLUSION:
      According to the results of this study, AmpC- beta-lactamase looks to be the main
      mechanism of resistance of Pseudomonas aeruginosa to cephalosporins and
      carbapenems in the study hospital.

PMID- 25848520
TI  - Prevalence assessment of magA gene and antimicrobial susceptibility of Klebsiella
      pneumoniae isolated from clinical specimens in Shahrekord, Iran.
AB  - BACKGROUND AND OBJECTIVES: Klebsiella pneumoniae (K. pneumoniae) is an
      opportunistic microorganism. This study aimed to investigate the presence of magA
      gene and antimicrobial susceptibility in K. pneumoniae. MATERIALS AND METHODS:
      clinical specimens were collected from hospitals of Shahrekord, Iran. Bacterial
      culture, biochemical diagnostic standard test, determination of antibiotic
      sensitivity, phenotypic testing hypermucoviscosity (HV) and polymerase chain
      reaction (PCR) was performed for isolation and characterization of K. pneumoniae.
      RESULTS: 173 samples were positive for K. pneumoniae. The highest and lowest
      rates of resistance were related to amoxicillin 79.19% and ciprofloxacin 15.60%,
      respectively. Also 4 samples were positive for magA gene. CONCLUSION: Based on
      our results, K. pneumoniae strains were resistant to different antibiotics.
      Knowing how to identify strains of K. pneumoniae, spreading of its virulence and
      also antimicrobial resistance genes can be useful in treatment of infection
      caused by this bacterium.

PMID- 25848521
TI  - Immunogenicity comparison of conjugate vaccines composed of alginate and
      lipopolysaccharide of Pseudomonas aeruginosa bound to diphtheria toxoid.
AB  - BACKGROUND AND OBJECTIVES: Treatment of Pseudomonas aeruginosa infections is
      greatly hampered by innate and acquired antibiotic resistance. The goal of this
      study was to compure the immunogenicity of conjugates of P. aeruginosa
      depolymerized alginate-diphtheria toxoid (D-ALGDT) and P. aeruginosa detoxified
      lipopolysaccharidediphtheria toxoid (D-LPSDT) in mouse model. MATERIALS AND
      METHODS: Alginate and LPS were purified from P. aeruginosa strain PAO1. The
      resulting depolymerized alginate (D-ALG) and detoxified LPS (D-LPS) were
      covalently coupled to diphtheria toxoid (DT) as a carrier protein with adipic
      acid dihydrazide (ADH) as a spacer molecule and carbodiimide as a linker.
      Sterility, safety and pyrogenicity tests were performed. 30 mice in two groups
      were immunized intraperitoneally on days 0, 14 and 28 with 10 MUg of D-ALGDT and
      D-LPSDT. Conjugates specific antibody levels were also determined by enzyme
      linked immunosorbent assay (ELISA). RESULTS: The conjugates were non-toxic and
      non-pyrogenic. Conjugates of D-ALGDT and D-LPSDT were shown to be safe and to
      elicit total IgG, IgM, IgA, IgG1, IgG2a, IgG2b and IgG3 antibodies in mice. ELISA
      results indicated that antibodies titer of D-ALGDT was more than D-LPSDT.
      CONCLUSION: Immunization with D-ALGDT showed significant increase in all types of
      antibodies titers in versus D-LPSDT, suggesting D-ALGDT as a vaccine candidate
      against P. aeruginosa infections.

PMID- 25848522
TI  - Immunological detection of 34 KDa outer membrane protein as a functional form of
      OipA in clinical isolates of Helicobacter pylori.
AB  - BACKGROUND AND OBJECTIVE: An outer membrane protein (OMP) of Helicobacter pylori
      namely OipA, is an important virulence factor associated with peptic ulcer and
      gastric cancer risks. The purpose of this study was to isolate the 34 KDa OMP of
      H. pylori and evaluate its immunogenicity in experimental animals for rapid
      detection of more virulent H. pylori isolates. MATERIAL AND METHODS: Sarcosine
      insoluble fraction of membrane proteins (OMPs) were prepared from 15 clinical
      isolates of H. pylori and their profiles were analyzed by SDS-PAGE. Two out of 15
      isolates which demonstrated higher expression for apparent 34 KDa proteins were
      selected. Under optimal conditions, 34 KDa protein was recovered from 5% SDS
      Agarose gel, purified and injected into the New Zealand white rabbits with
      Fruend's adjuvant in multiple stages with two weeks intervals. Collected
      antiserum was purified through affinity chromatography with Sepharose column and
      its titer was determined by ELISA. Specific immune response was demonstrated by
      Dot blot and western blotting methods. RESULTS: The titer of antibody was
      determined about 1/3000 and western blotting demonstrated a 34 KD-protein.
      Screening of various strains by Dot blot method for its presence showed that its
      expression was more frequent in strains isolated from the patients with more
      severe pathology. CONCLUSION: High titer obtained for pAbs antibody, suggested
      the high immunogenicity of this protein in experimental animals. Detection of 34
      KDa OMP in strains isolated from the patients with more severe pathology proposes
      the possible application of this pAbs in detecting more virulent strains of H.
      pylori.

PMID- 25848523
TI  - Application of Deletion- Targeted Multiplex PCR technique for detection of
      Mycobacterium tuberculosis Beijing strains in samples from tuberculosis patients.
AB  - BACKGROUND AND OBJECTIVE: Molecular epidemiological studies have shown that
      certain genotypes of Mycobacterium tuberculosis (MTB) are over-represented in
      limited geographical regions, suggesting of evolution of certain genotypes with
      increasing virulence and pathogenicity. Beijing strain of MTB was initially
      described by its potential to cause outbreaks worldwide and its association with
      drug resistance. Due to tuberculosis (TB)-related mortality which is associated
      with Beijing genotype, this study was designed with the aim to detect the MTB
      Beijing genotype in the region of study. MATERIALS AND METHODS: A total of 170
      clinical isolates of MTB were collected from the TB reference laboratory of
      Khuzestan province, Iran, over one year period from February 2010 to February
      2011. Phenotypic tests were used for preliminary detection of MTB. Culture
      positive MTB isolates were confirmed by multiplex PCR based on IS6110 gene with
      subsequent screening for resistance to isoniazid (INH), and rifampin (RIF) by PCR
      using relevant primers. Three set of primers were used to differentiate Beijing
      from non-Beijing strains by using Deletion- Targeted Multiplex (DTM) PCR.
      RESULTS: From 160 PCR-confirmed MTB isolates, 18 (11.25%) showed mutation in katG
      gene related to INH resistance and 20 (12.5%), associated with mutation in rpoB
      gene related to RIF resistance, and 8 (5%) were detected as Beijing strain using
      multiplex PCR. The majority of detected Beijing strains (6/8[75%]) comprised
      mutation in katG gene with the prevalent mutation specifically in codon 315. In 4
      Beijing strains (2.5%), mutation in rpoB gene were also detected. CONCLUSION:
      Using DTM- PCR, the rate of Beijing strains in the region of study was determined
      as 5%. Although for detection of MTB antimicrobial resistance, it is advised to
      use a combination of conventional antimicrobial susceptibility testing and
      molecular techniques, however for time saving, it seems that DTM-PCR, is a simple
      technique for use in areas of the world where Beijing strains are highly
      prevalent.

PMID- 25848524
TI  - Development and evaluation of a Quadruplex Taq Man real-time PCR assay for
      simultaneous detection of clinical isolates of Enterococcus faecalis,
      Enterococcus faecium and their vanA and vanB genotypes.
AB  - BACKGROUND AND OBJECTIVES: We developed and evaluated the utility of a quadruplex
      Taqman real-time PCR assay that allows simultaneous identification of vancomycin
      resistant genotypes and clinically relevant enterococci. MATERIALS AND METHODS:
      The specificity of the assay was tested using reference strains of vancomycin
      resistant and susceptible enterococci. In total, 193 clinical isolates were
      identified and subsequently genotyped using a Quadruplex Taqman real-time PCR
      assay and melting curve analysis. Representative Quadruplex Taqman real-time PCR
      amplification curve were obtained for Enterococcus faecium, Enterococcus
      faecalis, vanA-containing E. faecium, vanB-containing E. faecalis. RESULTS:
      Phenotypic and genotypic analysis of the isolates gave same results for 82
      enterococcal isolates, while in 5 isolates, they were inconsistent. We had three
      mixed strains, which were detected by the TaqMan real-time PCR assay and could
      not be identified correctly using phenotypic methods. CONCLUSION: Vancomycin
      resistant enterococci (VRE) genotyping and identification of clinically relevant
      enterococci were rapidly and correctly performed using TaqMan real-time multiplex
      real-time PCR assay.

PMID- 25848525
TI  - Comparison of four diagnostic methods for detection of methicillin resistant
      Staphylococcus aureus.
AB  - BACKGROUND AND OBJECTIVES: Methicillin-resistant Staphylococcus aureus (MRSA) is
      a well-known pathogen with a worldwide distribution. Given the increasing rate of
      MRSA infections, implementing of reliable, accurate and rapid testing for
      diagnosis of MRSA is necessary. The aim of this study was to compare four
      diagnostic methods for detection of MRSA isolates. MATERIALS AND METHODS: From
      December 2012 to April 2014, 120 S. aureus isolates were collected from three
      hospitals affiliated with Tehran University of Medical Sciences. MRSA isolates
      were detected by four different methods including cefoxitin disc diffusion test,
      oxacillin disc diffusion test, minimum inhibitory concentration (MIC) of
      oxacillin as determined by MIC test strip, and mecA detection by PCR. RESULTS:
      Out of 120 S. aureus isolates, cefoxitin disc diffusion test, oxacillin disc
      diffusion test and MIC test strip identified 60 (50%), 48 (40%), 55 (45.83%)
      isolates as MRSA, respectively. The sensitivity and specificity for oxacillin
      disc diffusion, cefoxitin disc diffusion and MIC of oxacillin were 80% and 100%,
      100% and 100%, and 91.6% and 100%, respectively. CONCLUSION: Cefoxitin disc
      diffusion test is reliable substitute for detection of MRSA in clinical
      laboratory where MIC detection and molecular methods are not accessible.

PMID- 25848526
TI  - Prevalence of enterotoxigenic Staphylococcus aureus in organic milk and cheese in
      Tabriz, Iran.
AB  - BACKGROUND AND OBJECTIVES: Staphylococcal food poisoning is a gastrointestinal
      disease, which is caused by consumption of contaminated food with enterotoxins
      produced by Staphylococcus aureus (SEs). Milk and its products are known sources
      of food borne diseases. This study was carried out to evaluate the prevalence of
      enterotoxigenic S. aureus strains in organic milk and cheese in Tabriz - Iran.
      MATERIALS AND METHODS: A total of 200 samples (100 milk samples and 100 cheese
      samples) were collected from farms and milk collection points in Tabriz - Iran.
      The samples were cultured and identified by standard bacteriological methods,
      then PCR was performed to detect sea gene. RESULTS AND CONCLUSION: Staphylococcus
      aureus was found in 27% of all samples (milk and cheese). Results of PCR showed
      that 12.96% of S. aureus isolates possessed sea gene. It suggested the potential
      public health threat of S. aureus resulting from contamination of dairy products.
      So, efforts are required to improve safety standards for preventing
      staphylococcal food poisoning.

PMID- 25848527
TI  - No evidence for occult HBV infection in hepatitis B vaccine non-responders.
AB  - BACKGROUND AND OBJECTIVE: Although hepatitis B vaccine immunogenicity is high,
      certain risk factors such as age, tobacco consumption, obesity and genetic
      background have been associated with low responsiveness to HBV vaccine. We aimed
      to evaluate the role of occult hepatitis B virus (HBV) infection in non-responder
      adults to HBV vaccine in a low endemic area for HBV. MATERIAL AND METHODS: A
      total of 52 subjects who were non-responder to HBV vaccine were enrolled in the
      study. HBsAg, anti-HBs and anti-HBc were tested in all subjects. The presence of
      HBV-DNA was determined in plasma samples by real-time PCR. RESULTS: A total of 52
      cases with median age 34 years were enrolled in the study. 63.5% of patients were
      male and 36.5% were female. Isolated anti-HBc (HBsAg negative, anti-HBs negative
      and anti-HBc positive) was detected in 3.8% of cases. HBV-DNA was not detected in
      our cases. CONCLUSION: This study showed no evidence of occult HBV infection in
      our HBV vaccine non-responders even in cases with isolated anti-HBc.

PMID- 25848528
TI  - Clinical and epidemiological features of the genus Malassezia in Iran.
AB  - BACKGROUND AND OBJECTIVES: The genus Malassezia contains an expanding list of
      lipophilic yeasts involve in the etiology of various superficial fungal
      infections. Pityriasis versicolor (PV) is the most prevalent Malassezia-related
      infection distributed worldwide. In the present study, clinical and
      epidemiological features of the genus Malassezia are discussed with special focus
      on PV in Iran. MATERIALS AND METHODS: During June 2012 to April 2013, among 713
      confirmed cases of fungal infections, 68 (9.5%) were diagnosed as PV by positive
      direct microscopy results in 20% potassium hydroxide (KOH) preparation of skin
      scrapings. All the specimens were cultured on modified Dixon agar and incubated
      at 32 degrees C for 10 days. Identification of the isolated yeasts was carried
      out based on macro- and microscopic morphology, catalase test, utilization of
      Tweens, polyethoxylated castor oil (EL slant), and hydrolysis of esculin and
      utilization of Tween-60 (TE slant). RESULTS: Out of 68 skin scrapings, 55 (80.9%)
      yielded yeast colonies on mDixon's agar which were finally identified as M.
      globosa (36.36%), M. pachydermatis (29.08%), M. furfur (23.65%), M. slooffiae
      (7.28%) and M. obtusa (3.64%). CONCLUSION: Results of the present study further
      indicate clinico-epidemiological importance of the genus Malassezia with growing
      importance of M. pachydermatis as a major species involve in the etiology of
      pityriasis versicolor. These findings are of major concern in management of
      Malassezia-related diseases.

PMID- 25848529
TI  - Isolation and molecular identification of deteriorating fungi from Cyrus the
      Great tomb stones.
AB  - BACKGROUND AND OBJECTIVES: Biodeterioration is an irreversible damage that is
      caused by colonization of microorganisms on the surface of different materials.
      Among all microorganisms, fungi play an important role in deterioration of
      materials. Fungi can colonize on stone surfaces and by secreting different
      enzymes, organic and inorganic acids and pigments, can cause bio-weathering and
      changing not only the substrate materials but the color of stones. Furthermore,
      fungal mycelia can penetrate into the internal surfaces of stones and change the
      interior chemical contents of stones. Pasargadae including Cyrus the Great Tomb
      is entitled by UNESCO as one of the World Heritage Sites. This study was focused
      on the identification of fungi that were colonized on the tomb limestone
      monument. MATERIALS AND METHODS: Sampling of stone was carried out to identify
      inhabiting molds and yeasts. biochemical and microscopic methods were used for
      isolated strains. In addition, the Polymerase Chain Reaction (PCR) and sequencing
      of the PCR products were done. Finally, phylogenic tree was constructed basde on
      the sequences of ITs region. RESULTS AND CONCLUSION: The common inhabiting fungi
      which isolated from the tomb limestone belong to Caldosporium sp., Embellisia
      sp., Cryptococcus sp., Candida sp., Meyerozyma sp., Arthirinium sp., Ulocladium
      sp., Fusarium sp., Humicola sp. and Pseudozyma sp.. Stereomicroscopic and
      Scanning Electron Microscope images and XRD, were taken from pieces of stone
      samples and indicated the severe pattern damages such as pitting,
      biomineralization, etching and sugaring on the surfaces of stones.

PMID- 25848530
TI  - Development and validation of a classification approach for extracting severity
      automatically from electronic health records.
AB  - BACKGROUND: Electronic Health Records (EHRs) contain a wealth of information
      useful for studying clinical phenotype-genotype relationships. Severity is
      important for distinguishing among phenotypes; however other severity indices
      classify patient-level severity (e.g., mild vs. acute dermatitis) rather than
      phenotype-level severity (e.g., acne vs. myocardial infarction). Phenotype-level
      severity is independent of the individual patient's state and is relative to
      other phenotypes. Further, phenotype-level severity does not change based on the
      individual patient. For example, acne is mild at the phenotype-level and relative
      to other phenotypes. Therefore, a given patient may have a severe form of acne
      (this is the patient-level severity), but this does not effect its overall
      designation as a mild phenotype at the phenotype-level. METHODS: We present a
      method for classifying severity at the phenotype-level that uses the Systemized
      Nomenclature of Medicine - Clinical Terms. Our method is called the
      Classification Approach for Extracting Severity Automatically from Electronic
      Health Records (CAESAR). CAESAR combines multiple severity measures - number of
      comorbidities, medications, procedures, cost, treatment time, and a proportional
      index term. CAESAR employs a random forest algorithm and these severity measures
      to discriminate between severe and mild phenotypes. RESULTS: Using a random
      forest algorithm and these severity measures as input, CAESAR differentiates
      between severe and mild phenotypes (sensitivity = 91.67, specificity = 77.78)
      when compared to a manually evaluated reference standard (k = 0.716).
      CONCLUSIONS: CAESAR enables researchers to measure phenotype severity from EHRs
      to identify phenotypes that are important for comparative effectiveness research.

PMID- 25848531
TI  - Pharmacological manipulation of transcription factor protein-protein
      interactions: opportunities and obstacles.
AB  - Much research on transcription factor biology and their genetic pathways has been
      undertaken over the last 30 years, especially in the field of developmental
      biology and cancer. Yet, very little is known about the molecular modalities of
      highly dynamic interactions between transcription factors, genomic DNA, and
      protein partners. Methodological breakthroughs such as RNA-seq (RNA-sequencing),
      ChIP-seq (chromatin immunoprecipitation sequencing), RIME (rapid
      immunoprecipitation mass spectrometry of endogenous proteins), and single
      molecule imaging will dramatically accelerate the discovery rate of their
      molecular mode of action in the next few years. From a pharmacological viewpoint,
      conventional methods used to target transcription factor activity with molecules
      mimicking endogenous ligands fail to achieve high specificity and are limited by
      a lack of identification of new molecular targets. Protein-protein interactions
      are likely to represent one of the next major classes of therapeutic targets.
      Transcription factors, known to act mostly via protein-protein interaction, may
      well be at the forefront of this type of drug development. One hurdle in this
      field remains the difficulty to collate structural data into meaningful
      information for rational drug design. Another hurdle is the lack of chemical
      libraries meeting the structural requirements of protein-protein interaction
      disruption. As more attempts at modulating transcription factor activity are
      undertaken, valuable knowledge will be accumulated on the modality of action
      required to modulate transcription and how these findings can be applied to
      developing transcription factor drugs. Key discoveries will spawn into new
      therapeutic approaches not only as anticancer targets but also for other
      indications, such as those with an inflammatory component including
      neurodegenerative disorders, diabetes, and chronic liver and kidney diseases. 

PMID- 25848533
TI  - Bone microdamage, remodeling and bone fragility: how much damage is too much
      damage?
AB  - Microdamage resulting from fatigue or 'wear and tear' loading contributes to bone
      fragility; however, the full extent of its influence is not completely
      understood. Linear microcracks (~50-100 MUm) and diffuse damage (clusters of
      sublamellar-sized cracks) are the two major bone microdamage types, each with
      different mechanical and biological consequences. Healthy bone, due to its
      numerous microstructural interfaces and its ability to affect matrix level
      repair, deals effectively with microdamage. From a material standpoint, healthy
      bone behaves much like engineering composites like carbon-fiber reinforced
      plastics. Both materials allow matrix damage to form during fatigue loading and
      use microstructural interfaces to dissipate energy and limit microcrack
      propagation to slow fracture. The terms fracture toughness and 'toughening
      mechanism', respectively, describe mechanical behavior and microstructural
      features that prevent crack growth and make it harder to fracture a material.
      Critically, toughness is independent of strength. In bone, primary toughening
      features include mineral and collagen interfaces, lamellae and tissue
      heterogeneity among osteons. The damage tolerance of bone and other composites
      can be overcome with sustained loading and/or matrix changes such that the
      microstructure no longer limits microcrack propagation. With reduced remodeling
      due to aging, disease or remodeling suppression, microdamage accumulation can
      occur along with loss of tissue heterogeneity. Both contribute additively to
      reduced fracture toughness. Thus, the answer to the key question for bone
      fragility of how much microdamage is too much is extremely complex. It ultimately
      depends on the interplay between matrix damage content, internal repair and
      effectiveness of matrix-toughening mechanisms. 

PMID- 25848532
TI  - Molecular alterations that drive breast cancer metastasis to bone.
AB  - Epithelial cancers including breast and prostate commonly progress to form
      incurable bone metastases. For this to occur, cancer cells must adapt their
      phenotype and behaviour to enable detachment from the primary tumour, invasion
      into the vasculature, and homing to and subsequent colonisation of bone. It is
      widely accepted that the metastatic process is driven by the transformation of
      cancer cells from a sessile epithelial to a motile mesenchymal phenotype through
      epithelial-mesenchymal transition (EMT). Dissemination of these motile cells into
      the circulation provides the conduit for cells to metastasise to distant organs.
      However, accumulating evidence suggests that EMT is not sufficient for metastasis
      to occur and that specific tissue-homing factors are required for tumour cells to
      lodge and grow in bone. Once tumour cells are disseminated in the bone
      environment, they can revert into an epithelial phenotype through the reverse
      process of mesenchymal-epithelial transition (MET) and form secondary tumours. In
      this review, we describe the molecular alterations undertaken by breast cancer
      cells at each stage of the metastatic cascade and discuss how these changes
      facilitate bone metastasis. 

PMID- 25848534
TI  - Role of syndecan-2 in osteoblast biology and pathology.
AB  - Syndecans 1-4 are a family of transmembrane proteins composed of a core protein
      and glycosaminoglycan chains. Although the four syndecans have common functions,
      they appear to be connected to different signaling pathways, and their expression
      occurs in a cell- and development-specific pattern. In contrast to other
      syndecans, syndecan-2 expression increases during osteoblast differentiation.
      Mechanistically, syndecan-2 exerts multiple functions in cells of the osteoblast
      lineage as it serves as a co-receptor for fibroblast growth factors and Wnt
      proteins and controls cell adhesion, proliferation, differentiation and
      apoptosis. Recent studies indicate that syndecan-2 also contributes to
      osteosarcoma cell response to cytotoxic agents through interactions with Wnt/beta
      catenin signaling. Here we summarize our current understanding of the role of
      syndecan-2 in the control of osteoblast biology and pathology and discuss how
      syndecan-2 acts as a modulator of the bone cell microenvironment. 

PMID- 25848536
TI  - Assessment of the therapeutic value of new medicines marketed in Australia.

PMID- 25848535
TI  - Metabolite profiling in posttraumatic stress disorder.
AB  - BACKGROUND: Traumatic stress does not only increase the risk for posttraumatic
      stress disorder (PTSD), but is also associated with adverse secondary physical
      health outcomes. Despite increasing efforts, we only begin to understand the
      underlying biomolecular processes. The hypothesis-free assessment of a wide range
      of metabolites (termed metabolite profiling) might contribute to the discovery of
      biological pathways underlying PTSD. METHODS: Here, we present the results of the
      first metabolite profiling study in PTSD, which investigated peripheral blood
      serum samples of 20 PTSD patients and 18 controls. We performed liquid
      chromatography (LC) coupled to Quadrupole/Time-Of-Flight (QTOF) mass
      spectrometry. Two complementary statistical approaches were used to identify
      metabolites associated with PTSD status including univariate analyses and Partial
      Least Squares Discriminant Analysis (PLS-DA). RESULTS: Thirteen metabolites
      displayed significant changes in PTSD, including four glycerophospholipids, and
      one metabolite involved in endocannabinoid signaling. A biomarker panel of 19
      metabolites classifies PTSD with 85% accuracy, while classification accuracy from
      the glycerophospholipid with the highest differentiating ability already reached
      82%. CONCLUSIONS: This study illustrates the feasibility and utility of
      metabolite profiling for PTSD and suggests lipid-derived and endocannabinoid
      signaling as potential biological pathways involved in trauma-associated
      pathophysiology.

PMID- 25848537
TI  - Response to Michael Wonder's comments on the article 'Assessment of the
      therapeutic value of new medicines marketed in Australia'.

PMID- 25848538
TI  - Antibiotic prescribing in women during and after delivery in a non-teaching,
      tertiary care hospital in Ujjain, India: a prospective cross-sectional study.
AB  - OBJECTIVES: Antibacterial drugs (hereafter referred to as antibiotics) are
      crucial to treat infections during delivery and postpartum period to reduce
      maternal mortality. Institutional deliveries have the potential to save lives of
      many women but extensive use of antibiotics, add to the development and spread of
      antibiotic resistance. The aim of this study was to present antibiotic
      prescribing among inpatients during and after delivery in a non-teaching,
      tertiary care hospital in the city of Ujjain, Madhya Pradesh, India. METHODS: A
      prospective cross-sectional study was conducted including women having had either
      a vaginal delivery or a cesarean section in the hospital. Trained nursing staff
      collected the data on daily bases, using a specific form attached to each patient
      file. Statistical analysis, including bivariate and multivariable logistic
      regression was conducted. RESULTS: Of the total 1077 women, 566 (53%) had a
      vaginal delivery and 511 (47%) had a cesarean section. Eighty-seven percent of
      the women that had a vaginal delivery and 98% of the women having a cesarean
      section were prescribed antibiotics. The mean number of days on antibiotics in
      hospital for the women with a vaginal delivery was 3.1 (+/-1.7) and for the women
      with cesarean section was 6.0 (+/-2.5). Twenty-eight percent of both the women
      with vaginal deliveries and the women with cesarean sections were prescribed
      antibiotics at discharge. The most commonly prescribed antibiotic group in the
      hospital for both the women that had a vaginal delivery and the women that had a
      cesarean section were third-generation cephalosporins (J01DD). The total number
      of defined daily doses (DDD) per100 bed days for women that had a vaginal
      delivery was 101, and 127 for women that had a cesarean section. CONCLUSIONS: The
      high percentage of women having had a vaginal delivery that received antibiotics
      and the deviation from recommendation for cesarean section in the hospital is a
      cause of concern. Improved maternal health and rational use of antibiotics are
      intertwined. Specific policy and guidelines on how to prescribe antibiotics
      during delivery at health care facilities are needed. Additionally, monitoring
      system of antibiotic prescribing and resistance needs to be developed and
      implemented.

PMID- 25848539
TI  - Malaria treatment policies and drug efficacy in Haiti from 1955-2012.
AB  - OBJECTIVES: Chloroquine (CQ), after 67 years of use in Haiti, is still part of
      the official treatment policy for malaria. Several countries around the world
      have used CQ in the past due to its low incidence of adverse events, therapeutic
      efficacy, and affordability, but were forced to switch treatment policy due to
      the development of widespread CQ resistance. The purpose of this paper was to
      compile literature on malaria treatment policies and antimalarial drug efficacy
      in Haiti over 67-year period. METHODS: A systematic review of PubMed, Web of
      Science, and the Armed Forces Pest Management Board, was conducted to find
      pertinent documents on national malaria treatment policies and antimalarial drug
      efficacy studies in Haiti between 1955 and 2012. A total of 329 citations and
      abstracts were reviewed independently by two researchers, of which thirty three
      met the final inclusion criteria of studies occurring in Haiti between 1955 and
      2012 which specifically discuss malaria treatment policies and drug efficacy.
      RESULTS: Results suggest that CQ has been the predominant antimalarial drug in
      use from 1955 to 2012. In 2010 single dose primaquine (PQ) was added to the
      national treatment policy, however it is not clear whether this new policy has
      been put into practice. CONCLUSIONS: Although no widespread CQ resistance has
      been reported, some studies have detected low levels of CQ resistance. Increased
      surveillance and monitoring for CQ resistance should be implemented in Haiti.

PMID- 25848540
TI  - Economics and industry do not mean ethical conduct in clinical trials.
AB  - Clinical trials present an ethical dilemma for pharmaceutical companies. While
      companies may want to undertake and report these trials in an ethical manner,
      negative results can significantly affect product sales. There is accumulating
      evidence that company-financed trials are biased in favor of the product that the
      company makes. Ethical conduct in this article is defined as whether the trials
      are conducted in the best interests of the participants and/or reported in the
      best interests of patients. Nine examples of how clinical trials are violating
      multiple articles in the Declaration of Helsinki are discussed using concrete
      case reports from the literature. The recognition of ethical problems in company
      run trials is not something new, but to date no meaningful action has been taken
      to resolve this issue. What is necessary is to separate the financing of clinical
      trials from their conduct. 

PMID- 25848542
TI  - A research agenda to promote affordable and quality assured medicines.
AB  - Promoting generic medicines to increase access to essential medicines is relevant
      to achieve the Millennium Development Goal (MDGs) and post 2015 goals. There are
      several barriers to encouraging wider use of generic medicines in health systems,
      e.g. the widely-held perception that low price equals low quality and
      misalignment of provider and consumer incentives. Overcoming the complex barriers
      and other challenges can be re-formulated as a 'generic medicine evidence-based
      policy agenda': (1) What policy and strategies can increase consumer trust in the
      quality of all medicines granted market authority including generic products? (2)
      Are there differences in prices between branded and unbranded generics? (3) What
      are synergies between policies that can enhance promoting of generic medicines
      effectively? Evaluating the policies promoting generic medicines will be critical
      to create evidence that countries can use to implement policies in their local
      settings. 

PMID- 25848541
TI  - Immigrant background and medicine use for aches: national representative study of
      adolescents.
AB  - OBJECTIVES: The aims of the study were to examine the association between
      immigrant background and medicine use for headache and stomach-ache among
      adolescents, and whether symptoms of headache and stomach-ache could explain the
      differences in medicine use. METHODS: We used data from the Danish contribution
      to the WHO-affiliated international cross-sectional survey Health Behaviour in
      School-aged Children (HBSC) in 2006. Among boys, a total of 4170 ethnic Danes,
      244 descendants of immigrants, and 224 immigrants participated. Among girls, 4310
      ethnic Danes, 264 descendants of immigrants, and 232 immigrants were included.
      The associations between migrant background and medicine use for headache and
      stomach-ache by means of multilevel multivariate logistic regression analyses
      adjusted for age group, symptoms and the clustering effect of school and
      stratified by sex due to interactions. RESULTS: Among boys, the risk of medicine
      use for stomach-ache was higher for immigrants (odds ratio (OR), 1.54; 95%
      confidence intervals (CI), 0.99-2.44)) and descendants (OR, 1.97 (1.33-2.94))
      compared to ethnic Danes. Similar associations were found for use of medicine for
      stomach-ache for immigrant girls (OR, 1.55 (1.12-2.15) and use of medicine for
      headache among boys (immigrants (OR, 1.36 (1.02-1.97 and descendants (1.48 (1.12
      1.97)). Symptoms of aches were all independently associated with medicine use.
      After adjusting for these factors the association between immigrant background
      and medicine use attenuated slightly. CONCLUSION: Among adolescents in Denmark,
      the risk of medicine use for headache and stomach-ache was higher for immigrants
      and descendants as compared to ethnic Danes, with the exception of medicine use
      for headache among girls.

PMID- 25848543
TI  - Stock-outs of antiretroviral drugs and coping strategies used to prevent changes
      in treatment regimens in Kinondoni District, Tanzania: a cross-sectional study.
AB  - OBJECTIVES: Since 2004, the government of Tanzania has been rolling out
      antiretroviral treatment programs all over the country. However, the capacity of
      the health system to cope with the rapid scale-up of these programs is a major
      concern, and problems may result in drug stock-outs that force changes in
      treatment regimens. This study aims to explore stock-outs of antiretroviral drugs
      and further determine the coping strategies employed to prevent changes in
      treatment regimens in HIV/AIDS care and treatment clinics in Kinondoni District,
      Dar es Salaam, Tanzania. METHODS: A cross-sectional study was conducted in 20
      HIV/AIDS care and treatment clinics. Interviews were conducted with the person in
      charge and a member of the pharmacy staff from each clinic using a pre-tested
      semi-structured interview guide. Verbal responses were transcribed, coded and
      analysed by thematic approach. Quantitative data were analysed using Excel
      spreadsheet (Microsoft Excel(r), Microsoft Corporation). RESULTS: The total
      number of clients enrolled in the visited clinics was 32,147, of whom 20,831
      (64.8%) had already been initiated onto antiretroviral therapies (ART). Stock-out
      of antiretroviral drugs was reported in 16 out of the 20 clinics, causing 210
      patients to change their ART regimens, during the 12 months preceding the survey.
      Inefficient supply systems, quantification problems and short expiry duration
      were cited as the main causes of stock-outs. The coping strategies utilised to
      prevent changes in ART regimens were: shortening of the refill period, borrowing
      and moving patients to other clinics. CONCLUSION: Changes in ART regimens due to
      stock-outs of antiretroviral drugs occurred in a small but significant number of
      patients. This increases the risk of the emergence of drug-resistant HIV strains.
      Healthcare workers use various coping strategies to prevent changes in ART
      regimens but, unfortunately, some of these strategies are likely to increase
      patient-borne costs, which may discourage them from attending their routine
      clinics, hence leading to unplanned treatment interruptions.

PMID- 25848544
TI  - An in-depth analysis of pharmaceutical regulation in the Republic of Moldova.
AB  - OBJECTIVE: Regulation of the pharmaceutical system is a crucial, yet often
      neglected, component in ensuring access to safe and effective medicines. The aim
      of this study was to provide an in-depth analysis of the existing pharmaceutical
      regulation, including recent changes, in the Republic of Moldova. METHODS: Data
      from field work conducted by the World Health Organization (WHO) together with a
      review of policy documents and quantitative secondary data analysis was used to
      achieve this aim. RESULTS: This analysis identified several ways in which
      pharmaceutical regulation affects availability of quality medicines in the
      Republic of Moldova. These include lack of full implementation bioequivalence
      requirements for generics registration, incomplete implementation of good
      manufacturing practices and no implementation of good distribution practices, use
      of quality control instead of quality assurance as a method to ensure quality of
      medicines, frequent change of power within the Medicines and Medical Devices
      Agency (MMDA) leading to lack of long-term strategy and plans, conflict of
      interest between the different functions of the MMDA, the lack of sufficient
      funding for the MMDA to conduct its activities and to invest in continuous
      training of its staff (particularly inspectors) and very weak post-marketing
      control. Notably, several improvements have been recently introduced, including a
      roadmap for change for the MMDA, the introduction of good manufacturing practices
      and the drafting of a quality manual for the Agency. CONCLUSION: Based on these
      findings the authors propose a set of priority actions to address existing gaps
      and draw lessons learned from other countries.

PMID- 25848545
TI  - The Papua New Guinea medical supply system - documenting opportunities and
      challenges to meet the Millennium Development Goals.
AB  - OBJECTIVES: Limited human resources are widely recognised as an impediment to
      achieving the health-related Millennium Development Goals in Pacific Island
      Countries, with the availability of medical supplies and suitably trained health
      personnel crucial to ensuring a well-functioning medical supply chain. This paper
      presents our findings as we seek to answer the research question 'What factors
      influence the availability of medical supplies within the health facilities of
      Papua New Guinea?' METHODS: We used a qualitative, triangulated strategy using
      semi-structured interviews, workplace observation and semi-structured focus
      groups. The parallel use of the interview tool and workplace observation tool
      allowed identification of 'know-do' gaps between what the interviewee said they
      did in their work practices, and the actual evidence of these practices. Focus
      groups provided further opportunities for raising and elaborating issues.
      RESULTS: During 2 weeks of data collection we conducted 17 interviews and 15
      observational workplace surveys in 15 facilities. Sixteen health personnel
      participated in 3 focus groups across 2 provinces and one district. An array of
      medical supply issues across all levels of the medical supply chain were
      revealed, including standard operating procedures, facilities, transport,
      emergency medical kits, the cold chain and record keeping. The influence of
      health worker training and competency was found to be common across all of these
      issues. CONCLUSION: The factors influencing the availability of medical supplies
      in PNG consist of a range of interrelating issues, consisting of both simple and
      complex problems involving the different levels and cadres of workers within the
      medical supply chain. Health systems sustainability theory suggests that a
      coordinated approach which addresses the inter-related nature of these issues,
      led by the PNG government and supported by suitable development partners, will be
      required for sustainable health systems change to occur. These changes are
      necessary for PNG to meet the health-related Millennium Development Goals.

PMID- 25848546
TI  - Medicines discarded in household garbage: analysis of a pharmaceutical waste
      sample in Vienna.
AB  - OBJECTIVES: To analyze a sample of pharmaceutical waste drawn from household
      garbage in Vienna, with the aim to learn whether and which medicines end up
      unused in normal household waste. METHODS: We obtained a pharmaceutical waste
      sample from the Vienna Municipal Waste Department. This was drawn by their staff
      in a representative search in October and November 2009. We did a manual
      investigation of the sample which contained packs and loose blisters, excluded
      medical devices and traced loose blisters back to medicines packs. We reported
      information on the prescription status, origin, therapeutic group, dose form,
      contents and expiry date. We performed descriptive statistics for the total data
      set and for sub-groups (e.g. items still containing some of original content).
      RESULTS: In total, 152 packs were identified, of which the majority was
      prescription-only medicines (74%). Cardiovascular medicines accounted for the
      highest share (24%). 87% of the packs were in oral form. 95% of the packs had not
      expired. 14.5% of the total data set contained contents but the range of content
      left in the packs varied. Results on the packs with contents differed from the
      total: the shares of Over-the Counter medicines (36%), of medicines of the
      respiratory system (18%) and of the musculo-skeletal system (18%), for dermal use
      (23%) and of expired medicines (19%) were higher compared to the full data set.
      CONCLUSIONS: The study showed that some medicines end up unused or partially used
      in normal household garbage in Vienna. Our results did not confirm speculations
      about a high percentage of unused medicines improperly discarded. There is room
      for improved patient information and counseling to enhance medication adherence
      and a proper discharge of medicines.

PMID- 25848547
TI  - Physicians' perception of generic and electronic prescribing: A descriptive study
      from Jordan.
AB  - OBJECTIVES: The aim of this study was to investigate Jordanian physicians'
      perception and attitudes toward generic medicines and generic substitution. It
      also aimed to examine factors that affect physicians' pattern of prescribing, and
      to evaluate their opinion regarding future introduction of Electronic Prescribing
      (EP) in Jordan. METHODS: A cross-sectional descriptive study involving Jordanian
      physicians working in both public and private sectors was undertaken, using a
      self-administrated anonymous questionnaire. Frequency tables, cross-tabulation
      and chi square tests were used for data analysis. The response rate was 75.2% (n
      = 376/500). RESULTS: Cost was claimed to be an important factor in the
      prescribing decision for 69.1% of the Jordanian physicians. The majority of
      physicians (77.4%) claimed that they often prescribe generic medicines. Jordanian
      physicians predominantly welcomed the implementation of an EP and International
      Nonproprietary Name (INN) prescribing systems with 92%, and 80.1% respectively.
      More than two thirds of the physicians (69.4%) accepted generic substitution by
      pharmacists, with a significant association with their employment sector;
      physicians who work in the private sector tended to oppose generic substitution
      compared with physicians who work in the public sector. Physicians mostly (72.1%)
      opposed that generic substitution should only be allowed upon patient request.
      CONCLUSIONS: Jordanian physicians have a positive attitude towards generic
      medications and high willingness and acceptance of strategies that encourage
      generic utilisation such as EP, INN prescribing and generic substitution. All
      these strategies would help reduce the high expenditure on medicines in Jordan.
      These findings would provide baseline data to policy makers to develop a robust
      generic policy to achieve greater clinical effectiveness and economic efficiency
      from medicines prescribing.

PMID- 25848548
TI  - The future of medicines use and access research: using the Journal of
      Pharmaceutical Policy and Practice as a platform for change.

PMID- 25848549
TI  - Pharmaceutical Policy Part 2 Pharmaceutical engagement and policy development: a
      framework for influence.
AB  - The formulation of pharmaceutical policy is a critical component of healthcare
      planning, made more important given that medicines are the ubiquitous technology
      in the diagnosis, treatment and prevention of disease and constitute a
      significant proportion of health care expenditure. Pharmacists need to inform
      policy development that will, in its implementation, offer opportunity to deliver
      greater rationality, safety, effectiveness and economy to the medicines use
      process and where patients experience enhanced health outcomes. This is the
      second of two articles directed to this specific issue focusing on how policy and
      strategic change can be affected. This is discussed from three overlapping
      perspectives - from the point of view of skills, that is, the skills or tactics
      needed to be employed to effect change; secondly, from a structural standpoint in
      terms of what positional arrangements exist that could be positively exploited;
      and thirdly, the subject, particularly its relevance to the contemporary
      situation. These approaches are then exemplified through a worked example on
      medication safety and its application in practice. 

PMID- 25848550
TI  - MRI demyelination pattern and clinical course in a child with cerebral X-linked
      adrenoleukodystrophy (X-ALD).
AB  - The clinical spectrum in boys with X-linked adrenoleukodystrophy (X-ALD) ranges
      from isolated adrenocortical insufficiency and slowly progressive myelopathy to
      devastating cerebral demyelination. In the individual case, the disease course
      still remains unpredictable. Research findings suggest an important role of brain
      magnetic resonance imaging (MRI) lesion patterns as prognostic markers for X-ALD.
      Hence, familiarity with imaging features of childhood X-ALD in combination with
      clinical manifestation is required in order to stratify affected patients for
      therapy. We report on MRI findings and clinical course of cerebral X-ALD in a
      young boy with a rare subtype of white matter demyelination. 

PMID- 25848551
TI  - Role of duration of catheterization and length of hospital stay on the rate of
      catheter-related hospital-acquired urinary tract infections.
AB  - OBJECTIVE: Our aim is to prove that duration of catheterization and length of
      hospital stay (LOS) are associated with the rate of hospital-acquired urinary
      tract infections (UTI), while taking into account type of urinary catheter used,
      the most common organisms found, patient diagnosis on admission, associated
      comorbidities, age, sex, precautions that should be taken to avoid UTI, and
      comparison with other studies. METHODS: The study was done in a university
      teaching hospital with a 920-bed capacity; this hospital is a tertiary care
      center in Riyadh, Saudi Arabia. The study was done on 250 selected patients
      during the year 2010 as a retrospective descriptive study. Patients were selected
      as purposive sample, all of them having been exposed to urinary catheterization;
      hospital-acquired UTI were found in 100 patients. Data were abstracted from the
      archived patients' files in the medical record department using the annual
      infection control logbook prepared by the infection control department. The data
      collected were demographic information about the patients, clinical condition
      (diagnosis and the LOS), and possible risk factors for infection such as duration
      of catheterization, exposure to invasive devices or surgical procedures, and
      medical condition. RESULTS: There was a statistically significant association
      between the rate of UTI and duration of catheterization: seven patients had UTI
      out of 46 catheterized patients (15%) at 3 days of catheterization, while 30
      patients had UTI out of 44 catheterized patients (68%) at 8 days of
      catheterization (median 8 days in infected patients versus 3 days in noninfected
      patients; P-value <0.05), which means that the longer the duration of
      catheterization, the higher the UTI rate. There was a statistically significant
      association between the rate of UTI and LOS: three patients had UTI out of 37
      catheterized patients (8%) at 10 days LOS, while 42 patients had UTI out of 49
      catheterized patients (85.7%) at 18 days LOS. The longer the LOS, the higher the
      UTI rate: LOS for each patient (median 18 days for infected patients versus 10
      days for noninfected patients; P-value <0.05), and number of hospital-acquired
      catheter-related UTI (100 patients had UTI out of 250 catheterized patients,
      P=0.04). CONCLUSION: Reduction of the duration of catheterization and LOS of the
      patient have a positive impact in reduction of catheter-related UTI.

PMID- 25848552
TI  - Exercise rehabilitation in era of convergence.

PMID- 25848553
TI  - eGEMs: Pragmatic Publishing to Build a Learning Health System.
AB  - The Electronic Data Methods (EDM) Forum announces the launch of eGEMs (Generating
      Evidence and Methods to improve patient outcomes), a new, free, open access, peer
      reviewed e-publication. eGEMs aims to disseminate innovative ideas about how
      electronic clinical data (ECD) can be leveraged in comparative effectiveness
      research (CER), patient-centered outcomes research (PCOR) and quality improvement
      (QI). eGEMs seeks submissions in four main topic areas: analytic methods,
      clinical informatics, governance, and the learning health system. The goal of
      eGEMs is ultimately to promote dialogue and the sharing of ideas between
      researchers and other stakeholders in a credible and timely way, extending the
      efforts of the EDM Forum. 

PMID- 25848554
TI  - Learning How to Learn: How AcademyHealth is Supporting Evidence Generation in a
      Transforming World.
AB  - The field of health services research faces significant challenges as it aims to
      address pressing issues of quality and cost in the US healthcare system. Major
      advances in the availability of electronic clinical data (ECD) provide the
      opportunity to address questions that are important to the recipients, providers,
      and purchasers of health care. This is where eGEMs has a role to play, meeting an
      expressed need in the scientific community by disseminating approaches and
      methods for using ECD. eGEMs can help researchers address these important
      questions and consider strategies to further improve the US healthcare system. 

PMID- 25848555
TI  - In Search of a Data-in-Once, Electronic Health Record-Linked, Multicenter
      Registry-How Far We Have Come and How Far We Still Have to Go.
AB  - The learning health system is a framework in which new knowledge is translated
      into general clinical practice and clinical practice serves as the engine to
      generate new evidence and knowledge. One type of learning health system is an
      electronic health record (EHR)-linked multicenter registry. Significant
      investment has been made in recent years to spur the adoption of EHRs and to fund
      the creation of health information exchanges. Yet, given this investment, are we
      any closer to achieving the vision of a learning health system? What are the
      areas of success? What challenges remain? To answer these questions and using an
      EHR-linked multicenter registry as a model, we define a set of requirements that
      need to be met in order to achieve the goals of the learning health system. We
      then evaluate progress along each dimension by detailing our efforts to create an
      EHR-linked multicenter registry for ImproveCareNow, a quality improvement and
      research network focused on improving outcomes for children with inflammatory
      bowel disease (IBD). 

PMID- 25848556
TI  - Effect identification in comparative effectiveness research.
AB  - The widespread adoption of electronic medical records means there are now vast
      data resources available for comparative effectiveness research (CER). In concert
      with conventional randomized controlled trials, CER holds great promise for
      advancing our understanding of how different therapeutic treatments yield
      different health outcomes in different settings and with different populations.
      But in a research culture fixated on estimating correlations and p-values, the
      threat of misinterpretation of results and improper CER inferences is troubling.
      Accordingly, this paper aims to shore up the inferential foundations of CER by
      introducing the fundamentals of effect identification, which is the process of
      identifying or teasing out empirically defensible causal effects from competing
      explanations. Three primary requirements of effect identification-positivity,
      exchangeability, and consistency- are explained and simple exampled are given.
      The take home message is that so-called big data from medical records may not
      yield better or more useful results. Advances will come only when the right
      question is addressed with the appropriate data and methods. 

PMID- 25848557
TI  - Ensuring Support for Research and Quality Improvement (QI) Networks: Four Pillars
      of Sustainability-An Emerging Framework.
AB  - Multi-institutional research and quality improvement (QI) projects using
      electronic clinical data (ECD) hold great promise for improving quality of care
      and patient outcomes but typically require significant infrastructure investments
      both to initiate and maintain the project over its duration. Consequently, it is
      important for these projects to think holistically about sustainability to ensure
      their long-term success. Four "pillars" of sustainability are discussed based on
      the experiences of EDM Forum grantees and other research and QI networks. These
      include trust and value, governance, management, and financial and administrative
      support. Two "foundational considerations," adaptive capacity and policy levers,
      are also discussed. 

PMID- 25848558
TI  - eGEMs: An Opportunity for Better Science.
AB  - eGEMs faces two early challenges in its effort to effort to disseminate knowledge
      and new ideas about the use of electronic clinical data for research: attracting
      readers and producing better science. The health services grey literature and the
      microchip industry are two areas of knowledge generation that provide important
      insight for how eGEMs can achieve these goals. In order to achieve its goals,
      eGEMs should aim to promote rapid sharing of ideas, engage sponsors and potential
      users of research findings early in the process, develop metrics for success to
      guide research efforts, and recruit diverse contributors. Success would allow for
      not just the generation of new research, but also new science, which has the
      potential to significantly improve patient outcomes. 

PMID- 25848559
TI  - Security approaches in using tablet computers for primary data collection in
      clinical research.
AB  - Next-generation tablets (iPads and Android tablets) may potentially improve the
      collection and management of clinical research data. The widespread adoption of
      tablets, coupled with decreased software and hardware costs, has led to increased
      consideration of tablets for primary research data collection. When using tablets
      for the Washington Heights/Inwood Infrastructure for Comparative Effectiveness
      Research (WICER) project, we found that the devices give rise to inherent
      security issues associated with the potential use of cloud-based data storage
      approaches. This paper identifies and describes major security considerations for
      primary data collection with tablets; proposes a set of architectural strategies
      for implementing data collection forms with tablet computers; and discusses the
      security, cost, and workflow of each strategy. The paper briefly reviews the
      strategies with respect to their implementation for three primary data collection
      activities for the WICER project. 

PMID- 25848560
TI  - Development and Implementation of an Electronic Decision Support to Manage the
      Health of a High-Risk Population: The enhanced Electronic Medical Record Aging
      Brain Care Software (eMR-ABC).
AB  - INTRODUCTION: Health care systems in the United States are transitioning from
      volume-based purchasing models to value-based purchasing models that demand both
      delivery of personalized care for each patient and cost-effective population
      health management. The enhanced medical record for aging brain care (eMR-ABC)
      software is an electronic decision support system that facilitates the management
      of a high-risk population suffering from aging brain disorders such as dementia.
      METHODS: Using the lenses of the Complex Adaptive System and the Reflective
      Adaptive Process, we assembled an interdisciplinary team of clinicians, health
      services researchers, and software developers who designed, implemented,
      evaluated, and continuously modified the eMR-ABC to meet the needs of care
      coordinators who manage the health of a targeted high-risk population. RESULTS:
      The eMR-ABC captures and monitors the cognitive, functional, behavioral, and
      psychological symptoms of a registry of patients suffering from dementia or
      depression as well as the burden of patients' family caregivers. It provides
      decision support to care coordinators to create a personalized care plan that
      includes evidence-based nonpharmacological protocols, self-management handouts,
      and alerts of medications with potentially adverse cognitive effects. The
      software's built-in engine tracks patient visits and on-demand functionality to
      generate population reports for specified indicators. DISCUSSION: Population
      health programs depend on data collection and information systems with the
      ability to provide valuable and timely feedback on an ongoing basis. Following
      these guidelines, the eMR-ABC was designed specifically to meet the management
      needs of a high-risk population.

PMID- 25848561
TI  - Data warehouse governance programs in healthcare settings: a literature review
      and a call to action.
AB  - PURPOSE: Given the extensive data stored in healthcare data warehouses, data
      warehouse governance policies are needed to ensure data integrity and privacy.
      This review examines the current state of the data warehouse governance
      literature as it applies to healthcare data warehouses, identifies knowledge
      gaps, provides recommendations, and suggests approaches for further research.
      METHODS: A comprehensive literature search using five data bases, journal article
      title-search, and citation searches was conducted between 1997 and 2012. Data
      warehouse governance documents from two healthcare systems in the USA were also
      reviewed. A modified version of nine components from the Data Governance
      Institute Framework for data warehouse governance guided the qualitative
      analysis. RESULTS: Fifteen articles were retrieved. Only three were related to
      healthcare settings, each of which addressed only one of the nine framework
      components. Of the remaining 12 articles, 10 addressed between one and seven
      framework components and the remainder addressed none. Each of the two data
      warehouse governance plans obtained from healthcare systems in the USA addressed
      a subset of the framework components, and between them they covered all nine.
      CONCLUSIONS: While published data warehouse governance policies are rare, the 15
      articles and two healthcare organizational documents reviewed in this study may
      provide guidance to creating such policies. Additional research is needed in this
      area to ensure that data warehouse governance polices are feasible and effective.
      The gap between the development of data warehouses in healthcare settings and
      formal governance policies is substantial, as evidenced by the sparse literature
      in this domain.

PMID- 25848562
TI  - Advances in Patient-Reported Outcomes: The NIH PROMIS((r)) Measures.
AB  - Patient-reported outcomes (PRO) are questionnaire measures of patients' symptoms,
      functioning, and health-related quality of life. They are designed to provide
      important clinical information that generally cannot be captured with objective
      medical testing. In 2004, the National Institutes of Health launched a research
      initiative to improve the clinical research enterprise by developing state-of-the
      art PROs. The NIH Patient-Reported Outcomes Measurement System (PROMIS) and
      Assessment Center are the products of that initiative. Adult, pediatric, and
      parent-proxy item banks have been developed by using contemporary psychometric
      methods, yielding rapid, accurate measurements. PROMIS currently provides tools
      for assessing physical, mental, and social health using short-form and computer
      adaptive testing methods. The PROMIS tools are being adopted for use in clinical
      trials and translational research. They are also being introduced in clinical
      medicine to assess a broad range of disease outcomes. Recent legislative
      developments in the United States support greater efforts to include patients'
      reports of health experience in order to evaluate treatment outcomes, engage in
      shared decision-making, and prioritize the focus of treatment. PROs have garnered
      increased attention by the Food and Drug Administration (FDA) for evaluating
      drugs and medical devices. Recent calls for comparative effectiveness research
      favor inclusion of PROs. PROs could also potentially improve quality of care and
      disease outcomes, provide patient-centered assessment for comparative
      effectiveness research, and enable a common metric for tracking outcomes across
      providers and medical systems. 

PMID- 25848564
TI  - Comparisons among Health Behavior Surveys: Implications for the Design of
      Informatics Infrastructures That Support Comparative Effectiveness Research.
AB  - INTRODUCTION: To address the electronic health data fragmentation that is a
      methodological limitation of comparative effectiveness research (CER), the
      Washington Heights Inwood Informatics Infrastructure for Comparative
      Effectiveness Research (WICER) project is creating a patient-centered research
      data warehouse (RDW) by linking electronic clinical data (ECD) from New York
      Presbyterian Hospital's clinical data warehouse with ECD from ambulatory care,
      long-term care, and home health settings and the WICER community health survey
      (CHS). The purposes of the research were to identify areas of overlap between the
      WICER CHS and two other surveys that include health behavior data (the Behavioral
      Risk Factor Surveillance System (BRFSS) Survey and the New York City Community
      Health Survey (NYC CHS)) and to identify gaps in the current WICER RDW that have
      the potential to affect patient-centered CER. METHODS: We compared items across
      the three surveys at the item and conceptual levels. We also compared WICER RDW
      (ECD and WICER CHS), BRFSS, and NYC CHS to the County Health Ranking framework.
      RESULTS: We found that 22 percent of WICER items were exact matches with BRFSS
      and that there were no exact matches between WICER CHS and NYC CHS items not also
      contained in BRFSS. CONCLUSIONS: The results suggest that BRFSS and, to a lesser
      extent, NYC CHS have the potential to serve as population comparisons for WICER
      CHS for some health behavior-related data and thus may be particularly useful for
      considering the generalizability of CER study findings. Except for one measure
      related to health behavior (motor vehicle crash deaths), the WICER RDW's
      comprehensive coverage supports the mortality, morbidity, and clinical care
      measures specified in the County Health Ranking framework but is deficient in
      terms of some socioeconomic factors and descriptions of the physical environment
      as captured in BRFSS. Linkage of these data in the WICER RDW through geocoding
      can potentially facilitate patient-centered CER that integrates important
      socioeconomic and physical environment influences on health outcomes. The
      research methods and findings may be relevant to others interested in either
      integrating health behavior data into RDWs to support patient-centered CER or
      conducting population-level comparisons.

PMID- 25848563
TI  - Recommendations for the use of operational electronic health record data in
      comparative effectiveness research.
AB  - There is an increasing amount of clinical data in operational electronic health
      record (EHR) systems. Such data provide substantial opportunities for their re
      use for many purposes, including comparative effectiveness research (CER). In a
      previous paper, we identified a number of caveats related to the use of such
      data, noting that they may be inaccurate, incomplete, transformed in ways that
      undermine their meaning, unrecoverable for research, of unknown provenance, of
      insufficient granularity, or incompatible with research protocols. In this paper,
      we provide recommendations for overcoming these caveats with the goal of
      leveraging such data to benefit CER and other health care activities. These
      recommendations include adaptation of "best evidence" approaches to use of data;
      processes to evaluate availability, completeness, quality, and transformability
      of data; creation of tools to manage data and their attributes; determination of
      metrics for assessing whether data are "research grade"; development of methods
      for comparative validation of data; construction of a methodology database for
      methods involving use of clinical data; standardized reporting methods for data
      and their attributes; appropriate use of informatics expertise; and a research
      agenda to determine biases inherent in operational data and to assess informatics
      approaches to their improvement. 

PMID- 25848565
TI  - Preparing Electronic Clinical Data for Quality Improvement and Comparative
      Effectiveness Research: The SCOAP CERTAIN Automation and Validation Project.
AB  - BACKGROUND: The field of clinical research informatics includes creation of
      clinical data repositories (CDRs) used to conduct quality improvement (QI)
      activities and comparative effectiveness research (CER). Ideally, CDR data are
      accurately and directly abstracted from disparate electronic health records
      (EHRs), across diverse health-systems. OBJECTIVE: Investigators from Washington
      State's Surgical Care Outcomes and Assessment Program (SCOAP) Comparative
      Effectiveness Research Translation Network (CERTAIN) are creating such a CDR.
      This manuscript describes the automation and validation methods used to create
      this digital infrastructure. METHODS: SCOAP is a QI benchmarking initiative. Data
      are manually abstracted from EHRs and entered into a data management system.
      CERTAIN investigators are now deploying Caradigm's AmalgaTM tool to facilitate
      automated abstraction of data from multiple, disparate EHRs. Concordance is
      calculated to compare data automatically to manually abstracted. Performance
      measures are calculated between Amalga and each parent EHR. Validation takes
      place in repeated loops, with improvements made over time. When automated
      abstraction reaches the current benchmark for abstraction accuracy - 95% - itwill
      'go-live' at each site. PROGRESS TO DATE: A technical analysis was completed at
      14 sites. Five sites are contributing; the remaining sites prioritized meeting
      Meaningful Use criteria. Participating sites are contributing 15-18 unique data
      feeds, totaling 13 surgical registry use cases. Common feeds are registration,
      laboratory, transcription/dictation, radiology, and medications. Approximately
      50% of 1,320 designated data elements are being automatically abstracted-25% from
      structured data; 25% from text mining. CONCLUSION: In semi-automating data
      abstraction and conducting a rigorous validation, CERTAIN investigators will semi
      automate data collection to conduct QI and CER, while advancing the Learning
      Healthcare System.

PMID- 25848566
TI  - Advancing user experience research to facilitate and enable patient-centered
      research: current state and future directions.
AB  - Human-computer interaction and related areas of user experience (UX) research,
      such as human factors, workflow evaluation, and data visualization, are thus
      essential to presenting data in ways that can further the analysis of complex
      data sets such as those used in patient-centered research. However, a review of
      available data on the state of UX research as it relates to patient-centered
      research demonstrates a significant underinvestment and consequently a large gap
      in knowledge generation. In response, this report explores trends in funding and
      research productivity focused on UX and patient-centered research and then
      presents a set of recommendations to advance innovation at this important
      intersection point. Ultimately, the aim is to catalyze a community-wide dialogue
      concerning future directions for research and innovation in UX as it applies to
      patient-centered research. 

PMID- 25848568
TI  - eGEMs: Pathways to Success for Multisite Clinical Data Research.
AB  - There are numerous and significant challenges associated with leveraging
      electronic clinical data (ECD) for purposes beyond treating an individual patient
      and getting paid for that care. Optimizing this secondary use of clinical data is
      a key underpinning of many health reform goals and triggers numerous issues
      related to data stewardship and, more broadly, data governance. These challenges
      often involve legal, policy, and procedural issues related to the access, use,
      and disclosure of electronic health record (EHR) data for quality improvement and
      research. This paper contributes to the ongoing discussion of health data
      governance by detailing the experiences of nine multisite research initiatives
      across the country. The rich set of experiences from these initiatives, as well
      as a number of resources used by project participants to work through various
      challenges, are documented and collected here for others wishing to learn from
      their collective efforts. The paper does not attempt to catalog the full spectrum
      of governance issues that could potentially surface in the course of multisite
      research projects using ECD. Rather, the goal was to provide a snapshot in time
      of data-sharing challenges and navigation strategies, as well as validation that
      privacy-protective, legally compliant clinical data sharing across sites is
      currently possible. Finally, the paper also provides a foundation and framing for
      a broader community resource on governance-a "governance toolkit"-that will
      create a virtual space for the further discussion and sharing of promising
      practices. 

PMID- 25848567
TI  - Scalable Architecture for Federated Translational Inquiries Network (SAFTINet)
      Technology Infrastructure for a Distributed Data Network.
AB  - INTRODUCTION: Distributed Data Networks (DDNs) offer infrastructure solutions for
      sharing electronic health data from across disparate data sources to support
      comparative effectiveness research. Data sharing mechanisms must address
      technical and governance concerns stemming from network security and data
      disclosure laws and best practices, such as HIPAA. METHODS: The Scalable
      Architecture for Federated Translational Inquiries Network (SAFTINet) deploys
      TRIAD grid technology, a common data model, detailed technical documentation, and
      custom software for data harmonization to facilitate data sharing in
      collaboration with stakeholders in the care of safety net populations. Data
      sharing partners host TRIAD grid nodes containing harmonized clinical data within
      their internal or hosted network environments. Authorized users can use a central
      web-based query system to request analytic data sets. DISCUSSION: SAFTINet DDN
      infrastructure achieved a number of data sharing objectives, including scalable
      and sustainable systems for ensuring harmonized data structures and terminologies
      and secure distributed queries. Initial implementation challenges were resolved
      through iterative discussions, development and implementation of technical
      documentation, governance, and technology solutions.

PMID- 25848569
TI  - Electronic Data Capture through Total Joint Replacement Registries.
AB  - The move toward adoption and implementation of electronic health records (EHR)
      provides an opportunity in the United States to use electronic clinical data
      (ECD) to better understand patient outcomes and to improve the quality and
      efficiency of medical care. Within the field of orthopedics, national joint
      replacement registries have been shown in other countries to improve clinical
      decision-making and outcomes after joint arthroplasty. Thus, there is increasing
      interest among U.S. clinical investigators and policymakers to utilize ECD to
      develop national and regional joint replacement registries. We discuss our
      experience with integrating electronic data capture and reporting methodology
      into the California Joint Replacement Registry and American Joint Replacement
      Registry initiatives. The use of ECD for joint replacement registries will better
      facilitate multi-stakeholder collaboration, improve the quality of care, reduce
      medical spending, and foster customized evidence-based clinical decision-making. 

PMID- 25848570
TI  - Moving to a user-driven research paradigm.
AB  - The traditional "bench-to-bedside" paradigm for clinical research has been
      successfully used for many decades. This model of knowledge generation has led to
      discoveries that have enhanced the quality and length of life. The combination of
      changes in research practice and in health care delivery, growing complexity in
      decision-making, increasing use of electronic health records (EHR), and growing
      resource constraints necessitate a shift to a user-driven research paradigm to
      generate new knowledge. This conceptual framework was created to clarify the
      perspective of the decision makers as well as the range of factors and the
      variability in thresholds used to make decisions. This framework may help
      researchers in creating actionable information to meet the needs of decision
      makers, which is needed for the transition to a user-driven research paradigm.
      Further, it is important to create an appropriate set of incentives to facilitate
      this transition to a user-driven research paradigm. 

PMID- 25848571
TI  - Applications of electronic health information in public health: uses,
      opportunities & barriers.
AB  - Electronic health information systems can reshape the practice of public health
      including public health surveillance, disease and injury investigation and
      control, decision making, quality assurance, and policy development. While these
      opportunities are potentially transformative, and the federal program for the
      Meaningful Use (MU) of electronic health records (EHRs) has included important
      public health components, significant barriers remain. Unlike incentives in the
      clinical care system, scant funding is available to public health departments to
      develop the necessary information infrastructure and workforce capacity to
      capitalize on EHRs, personal health records, or Big Data. Current EHR systems are
      primarily built to serve clinical systems and practice rather than being
      structured for public health use. In addition, there are policy issues concerning
      how broadly the data can be used by public health officials. As these issues are
      resolved and workable solutions emerge, they should yield a more efficient and
      effective public health system. 

PMID- 25848572
TI  - Health-weighted Composite Quality Metrics Offer Promise to Improve Health
      Outcomes in a Learning Health System.
AB  - Health system leaders sometimes adopt quality metrics without robust supporting
      evidence of improvements in quality and/or quantity of life, which may impair
      rather than facilitate improved health outcomes. In brief, there is now no easy
      way to measure how much "health" is conferred by a health system. However, we
      argue that this goal is achievable. Health-weighted composite quality metrics
      have the potential to measure "health" by synthesizing individual evidence-based
      quality metrics into a summary measure, utilizing relative weightings that
      reflect the relative amount of health benefit conferred by each constituent
      quality metric. Previously, it has been challenging to create health-weighted
      composite quality metrics because of methodological and data limitations.
      However, advances in health information technology and mathematical modeling of
      disease progression promise to help mitigate these challenges by making patient
      level data (eg, from the electronic health record and mobile health (mHealth)
      more accessible and more actionable for use. Accordingly, it may now be possible
      to use health information technology to calculate and track a health-weighted
      composite quality metric for each patient that reflects the health benefit
      conferred to that patient by the health system. These health-weighted composite
      quality metrics can be employed for a multitude of important aims that improve
      health outcomes, including quality evaluation, population health maximization,
      health disparity attenuation, panel management, resource allocation, and
      personalization of care. We describe the necessary attributes, the possible uses,
      and the likely limitations and challenges of health-weighted composite quality
      metrics using patient-level health data. 

PMID- 25848573
TI  - How electronic clinical data can improve health technology assessment.
AB  - Health technology assessments represent comprehensive summaries of available
      evidence and information on a technology. They are used by medical decision
      makers in a variety of ways, including diagnostic testing, treatment selection,
      care management, patient perspectives, patient safety, insurance coverage,
      pharmaceutical innovation, equipment planning, device purchasing, and total cost
      of-care. Electronic clinical data, which are captured routinely by clinicians and
      hospitals, are only rarely incorporated into formal health technology
      assessments. This disconnect reveals a key opportunity. In this paper, we discuss
      current uses of electronic clinical data, several benefits of including it in
      health technology assessments, potential pitfalls of that inclusion, and the
      implications for better medical decisions. 

PMID- 25848574
TI  - Achieving the Promise of Electronic Health Record-enabled Quality Measurement: a
      Measure Developer's Perspective.
AB  - Electronic health record (EHR) systems support local quality improvement efforts
      by health care organizations and provide the opportunity to address national
      priority areas for quality measurement, such as specialty care, overuse and
      efficiency, coordination of care, change over time and patient- reported outcomes
      (PROs). However, variations in provider workflow and documentation habits,
      adoption of advanced EHR functions and exchange of interoperable data, and
      eMeasure specification standards affect the ability to develop and test measures
      that target these high priority areas for improvement. Measure developers are
      working with providers, national standards organizations, and other eMeasure
      stakeholders to address these challenges and support learning health
      organizations in using EHR-based measurement to improve quality. 

PMID- 25848575
TI  - Ways decision makers can use evidence to improve patient outcomes in learning
      health systems: a message from the guest editor.

PMID- 25848576
TI  - Developing a fully integrated medical transport record to support comparative
      effectiveness research for patients undergoing medical transport.
AB  - The consolidation of health care systems to develop centers of clinical
      excellence has led to an increased reliance on medical transport to move patients
      requiring time-sensitive interventions and specialized treatments. There is a
      paucity of outcomes data, specifically comparative effectiveness research,
      related to the efficacy of different transport services and the overall morbidity
      and mortality of patients that undergo medical transfer. The rapid development of
      electronic medical record (EMR) use has also occurred with transport charting.
      However, limited studies have incorporated transport chart data in outcomes
      analyses. We have begun development of a fully integrated medical transport
      record, combining transport and hospitals EMRs, to support research efforts and
      develop clinical decision support tools for transported patients. In this paper,
      we describe the elements necessary to develop a fully integrated medical
      transport EMR to support the conduct of comparative effectiveness research,
      outline the current limitations and challenges, and provide insight into the
      future direction in developing clinical decision support tools for patients
      requiring transport. 

PMID- 25848577
TI  - Medical home characteristics and asthma control: a prospective, observational
      cohort study protocol.
AB  - BACKGROUND: This paper describes the methods for an observational comparative
      effectiveness research study designed to test the association between practice
      level medical home characteristics and asthma control in children and adults
      receiving care in safety-net primary care practices. METHODS: This is a
      prospective, longitudinal cohort study, utilizing survey methodologies and
      secondary analysis of existing structured clinical, administrative, and claims
      data. The Scalable Architecture for Federated Translational Inquiries Network
      (SAFTINet) is a safety net-oriented, primary care practice-based research
      network, with federated databases containing electronic health record (EHR) and
      Medicaid claims data. Data from approximately 20,000 patients from 50 practices
      in four healthcare organizations will be included. Practice-level medical home
      characteristics will be correlated with patient-level asthma outcomes,
      controlling for potential confounding variables, using a clustered design. Linear
      and non-linear mixed models will be used for analysis. Study inception was July
      1, 2012. A causal graph theory approach was used to guide covariate selection to
      control for bias and confounding. DISCUSSION: Strengths of this design include a
      priori specification of hypotheses and methods, a large sample of patients with
      asthma cared for in safety-net practices, the study of real-world variations in
      the implementation of the medical home concept, and the innovative use of a
      combination of claims data, patient-reported data, clinical data from EHRs, and
      practice-level surveys. We address limitations in causal inference using theory,
      design and analysis.

PMID- 25848579
TI  - Using multifactorial experiments for comparative effectiveness research in
      physician practices with electronic health record.
AB  - Two key challenges related to conducting comparative effectiveness research are
      the lack of available data and the lack of rigorous techniques for efficiently
      and quickly testing the effectiveness of the many possible ways of implementing
      components of care. The confluence of two things offers the promise of overcoming
      these challenges: (1) the increased adoption of electronic health records (EHRs),
      which can provide easier access to clinical information, and (2) burgeoning
      appreciation for an under-used but powerful statistical research and evaluation
      method for multifactor interventions known as multifactor experimental design.
      The use of multifactorial experiments paired with EHR data has great potential to
      help providers conduct rapid-cycle comparative effectiveness research and examine
      alternative ways of implementing care. Its power is its ability to enable
      scientifically rigorous testing of many facets of care provision simultaneously
      in real-world settings where change is ongoing. In this paper, we identify the
      opportunities for using efficient multifactorial designs and EHR data to evaluate
      quality-improvement efforts in physician practices. We illustrate the power of
      multifactorial designs through several examples relevant to physician practices
      with EHRs, such as evaluating clinical decision support features and studying
      components of a patient-centered medical home. 

PMID- 25848578
TI  - Strategies for handling missing data in electronic health record derived data.
AB  - Electronic health records (EHRs) present a wealth of data that are vital for
      improving patient-centered outcomes, although the data can present significant
      statistical challenges. In particular, EHR data contains substantial missing
      information that if left unaddressed could reduce the validity of conclusions
      drawn. Properly addressing the missing data issue in EHR data is complicated by
      the fact that it is sometimes difficult to differentiate between missing data and
      a negative value. For example, a patient without a documented history of heart
      failure may truly not have disease or the clinician may have simply not
      documented the condition. Approaches for reducing missing data in EHR systems
      come from multiple angles, including: increasing structured data documentation,
      reducing data input errors, and utilization of text parsing / natural language
      processing. This paper focuses on the analytical approaches for handling missing
      data, primarily multiple imputation. The broad range of variables available in
      typical EHR systems provide a wealth of information for mitigating potential
      biases caused by missing data. The probability of missing data may be linked to
      disease severity and healthcare utilization since unhealthier patients are more
      likely to have comorbidities and each interaction with the health care system
      provides an opportunity for documentation. Therefore, any imputation routine
      should include predictor variables that assess overall health status (e.g.
      Charlson Comorbidity Index) and healthcare utilization (e.g. number of
      encounters) even when these comorbidities and patient encounters are unrelated to
      the disease of interest. Linking the EHR data with other sources of information
      (e.g. National Death Index and census data) can also provide less biased
      variables for imputation. Additional methodological research with EHR data and
      improved epidemiological training of clinical investigators is warranted. 

PMID- 25848580
TI  - Methods for estimating kidney disease stage transition probabilities using
      electronic medical records.
AB  - Chronic diseases are often described by stages of severity. Clinical decisions
      about what to do are influenced by the stage, whether a patient is progressing,
      and the rate of progression. For chronic kidney disease (CKD), relatively little
      is known about the transition rates between stages. To address this, we used
      electronic health records (EHR) data on a large primary care population, which
      should have the advantage of having both sufficient follow-up time and sample
      size to reliably estimate transition rates for CKD. However, EHR data have some
      features that threaten the validity of any analysis. In particular, the timing
      and frequency of laboratory values and clinical measurements are not determined a
      priori by research investigators, but rather, depend on many factors, including
      the current health of the patient. We developed an approach for estimating CKD
      stage transition rates using hidden Markov models (HMMs), when the level of
      information and observation time vary among individuals. To estimate the HMMs in
      a computationally manageable way, we used a "discretization" method to transform
      daily data into intervals of 30 days, 90 days, or 180 days. We assessed the
      accuracy and computation time of this method via simulation studies. We also used
      simulations to study the effect of informative observation times on the estimated
      transition rates. Our simulation results showed good performance of the method,
      even when missing data are non-ignorable. We applied the methods to EHR data from
      over 60,000 primary care patients who have chronic kidney disease (stage 2 and
      above). We estimated transition rates between six underlying disease states. The
      results were similar for men and women. 

PMID- 25848581
TI  - New analytical methods for a learning healthcare system: a message from the guest
      editor.

PMID- 25848582
TI  - Validation of Diagnostic and Procedural Codes for Identification of Acute
      Cardiovascular Events in US Veterans with Rheumatoid Arthritis.
AB  - OBJECTIVE: To assess the accuracy of International Classification of Diseases,
      Ninth Revision, and Current Procedural Terminology codes for identifying
      cardiovascular (CV) events (myocardial infarction [MI], stroke, coronary artery
      bypass graft [CABG], and percutaneous coronary intervention [PCI]) in enrollees
      of the Veterans Affairs Rheumatoid Arthritis (VARA) registry. DESIGN: We
      performed a validation study from VARA enrollment until 6/1/2010 to compare the
      accuracy of CV events in those with and without CV-event coding in inpatient and
      outpatient records to evaluate for CV events +/- 3 months of the coding. The
      positive predictive value (PPV) was calculated, and codes with a PPV >=50% were
      included in a composite coding algorithm. RESULTS: We evaluated 107 individuals
      for 21 CV-event codes and 60 individuals without CV-event coding. The PPV varied
      between 0-100%. Composite coding algorithms' PPV ranged from 70-100%.
      CONCLUSIONS: Validation of these algorithms allows for identification of acute CV
      events with known accuracy. The sensitivity and PPV of coding algorithms for CABG
      and PCI exceed that of stroke and MI.

PMID- 25848583
TI  - A case study of pediatric asthma alerts from the beacon community program in
      cincinnati: technology is just the first step.
AB  - INTRODUCTION: The Beacon Community in Cincinnati, Ohio was an innovative,
      community-wide initiative to use technology to transform care. One important
      feature was the development of regional alerts to notify practices when patients
      were hospitalized or seen in the emergency department. The purpose of this paper
      is to describe the way in which technology engages the improvement process, and
      to describe the early stages of learning how to use technology to enhance quality
      improvement. METHODS: We interviewed key Beacon leaders as well as providers and
      office staff in selected practices. We also collected preliminary data from
      practices that reflected handling of alerts, including the number of asthma
      related alerts received and followed up. RESULTS: Regional alerts, supplied by
      the community-wide health information exchange, were a significant addition to
      the quality improvement effort in that they enabled practices to identify and
      follow up with additional children at risk. An important finding was the
      substantial effort at the practice level to integrate technology into ongoing
      patient care. CONCLUSIONS: Developing the technology for community wide alerts
      represented a significant endeavor in the Cincinnati Beacon Community. However,
      the technology was just the first step. Despite extra effort and time required on
      the part of individual practices, they reported that the value of having alerts
      was high. Hospital and ED visits represent some of the most costly aspects of
      care, and an efficient process for intervening with children using these costly
      services was seen as of significant value.

PMID- 25848585
TI  - Validity of medical chart weights and heights for obese pregnant women.
AB  - OBJECTIVE: To determine the validity of adult body weights and heights recorded
      in electronic medical records (EMRs) in the course of routine medical care.
      BACKGROUND: EMRs allow the potential use of data collected in the course of
      routine medical care for a variety of research applications in many fields
      including epidemiology and comparative effectiveness studies. However,
      researchers familiar with carefully controlled measurement protocols typically
      used in clinical trials may question the validity of data collected in the course
      of routine clinical care. METHODS: Weights and heights collected during a
      research project that focused on weight gain during pregnancy were compared to
      weight and height measurements coincidently recorded in the research
      participant's medical records. For weight measures (N=102), data recorded within
      +/-14 days were compared, and for height measures (N=114), data recorded within
      +/-5 years were compared. We assessed agreement between medical and research
      measurements using the concordance and intraclass correlation coefficients, and
      Bland and Altman's limits of agreement. FINDINGS: The mean research and medical
      record weight measurements were 99.3 kg and 99.2 kg, respectively. The
      concordance and intraclass correlation coefficients for weight had similar
      estimates of .999 and 95 percent confidence intervals [.998, .999]. The 95
      percent limits of agreement were -1.5 kg and +1.7 kg. The mean research and
      medical height measurements were 1.646 m and 1.654 m, respectively, and the
      concordance and intraclass correlation coefficients for height were .941 and
      .942, respectively. The 95 percent limits of agreement were -.031 m and +.047 m.
      CONCLUSIONS: For pregnant women, body weights documented in the medical record
      are exchangeable with body weights recorded in a research setting. Height
      measurements recorded in the medical records were not in as close agreement as
      weights, but concordance between medical record and research height measurements
      are high enough to allow them to be used epidemiological and comparative
      effectiveness research.

PMID- 25848584
TI  - The HMO Research Network Virtual Data Warehouse: A Public Data Model to Support
      Collaboration.
AB  - The HMO Research Network (HMORN) Virtual Data Warehouse (VDW) is a public, non
      proprietary, research-focused data model implemented at 17 health care systems
      across the United States. The HMORN has created a governance structure and
      specified policies concerning the VDW's content, development, implementation, and
      quality assurance. Data extracted from the VDW have been used by thousands of
      studies published in peer-reviewed journal articles. Advances in software
      supporting care delivery and claims processing and the availability of new data
      sources have greatly expanded the data available for research, but substantially
      increased the complexity of data management. The VDW data model incorporates
      software and data advances to ensure that comprehensive, up-to-date data of known
      quality are available for research. VDW governance works to accommodate new data
      and system complexities. This article highlights the HMORN VDW data model, its
      governance principles, data content, and quality assurance procedures. Our goal
      is to share the VDW data model and its operations to those wishing to implement a
      distributed interoperable health care data system. 

PMID- 25848586
TI  - Development of a web service for analysis in a distributed network.
AB  - OBJECTIVE: We describe functional specifications and practicalities in the
      software development process for a web service that allows the construction of
      the multivariate logistic regression model, Grid Logistic Regression (GLORE), by
      aggregating partial estimates from distributed sites, with no exchange of patient
      level data. BACKGROUND: We recently developed and published a web service for
      model construction and data analysis in a distributed environment. This recent
      paper provided an overview of the system that is useful for users, but included
      very few details that are relevant for biomedical informatics developers or
      network security personnel who may be interested in implementing this or similar
      systems. We focus here on how the system was conceived and implemented. METHODS:
      We followed a two-stage development approach by first implementing the backbone
      system and incrementally improving the user experience through interactions with
      potential users during the development. Our system went through various stages
      such as concept proof, algorithm validation, user interface development, and
      system testing. We used the Zoho Project management system to track tasks and
      milestones. We leveraged Google Code and Apache Subversion to share code among
      team members, and developed an applet-servlet architecture to support the cross
      platform deployment. DISCUSSION: During the development process, we encountered
      challenges such as Information Technology (IT) infrastructure gaps and limited
      team experience in user-interface design. We figured out solutions as well as
      enabling factors to support the translation of an innovative privacy-preserving,
      distributed modeling technology into a working prototype. CONCLUSION: Using GLORE
      (a distributed model that we developed earlier) as a pilot example, we
      demonstrated the feasibility of building and integrating distributed modeling
      technology into a usable framework that can support privacy-preserving,
      distributed data analysis among researchers at geographically dispersed
      institutes.

PMID- 25848587
TI  - Medicaid medical directors quality improvement studies: a case study of evolving
      methods for a research network.
AB  - OBJECTIVE: To describe the evolution of methods and share lessons learned from
      conducting multi-state studies with Medicaid Medical Directors (MMD) using state
      administrative data. There was a great need for these studies, but also much to
      be learned about conducting network-based research and ensuring comparability of
      results. METHODS: This was a network-level case study. The findings were drawn
      from the experience developing and executing network analyses with the MMDs, as
      well as from participant feedback on lessons learned. For the latter, nine
      interviews with MMD project leads, state data analysts, and outside researchers
      involved with the projects were conducted. Interviews were transcribed, coded and
      analyzed using NVivo 10.0 analytic software. FINDINGS: MMD study methodology
      involved many steps: developing research questions, defining data specifications,
      organizing an aggregated data collection spreadsheet form, assuring quality
      through review, and analyzing and reporting state data at the national level.
      State analysts extracted the data from their state Medicaid administrative
      (claims) databases (and sometimes other datasets). Analysis at the national level
      aggregated state data overall, by demographics and other sub groups, and
      displayed descriptive statistics and cross-tabs. CONCLUSIONS: Projects in the MMD
      multi-state network address high-priority clinical issues in Medicaid and impact
      quality of care through sharing of data and policies among states. Further, these
      studies contribute not only to high-quality, cost-effective health care for
      Medicaid beneficiaries, but also add to our knowledge of network-based research.
      Continuation of these studies requires funding for a permanent research
      infrastructure nationally, as well as at the state-level to strengthen capacity.

PMID- 25848588
TI  - Electronic Clinical Surveillance to Improve Outpatient Care: Diverse Applications
      within an Integrated Delivery System.
AB  - Efforts to improve patient safety have largely focused on inpatient or emergency
      settings, but the importance of patient safety in ambulatory care is increasingly
      being recognized as a key component of overall health care quality. Care gaps in
      outpatient settings may include missed diagnoses, medication errors, or
      insufficient monitoring of patients with chronic conditions or on certain
      medications. Further, care gaps may occur across a wide range of clinical
      conditions. We report here an innovative approach to improve patient safety in
      ambulatory settings - the Kaiser Permanente Southern California (KPSC) Outpatient
      Safety Net Program - which leverages electronic health information to efficiently
      identify and address a variety of potential care gaps across different clinical
      conditions. Between 2006 and 2012, the KPSC Outpatient Safety Net Program
      implemented 24 distinct electronic clinical surveillance programs, which
      routinely scan the electronic health record to identify patients with a
      particular condition or event. For example, electronic clinical surveillance may
      be used to scan for harmful medication interactions or potentially missed
      diagnoses (e.g., abnormal test results without evidence of subsequent care). Keys
      to the success of the program include strong leadership support, a proactive
      clinical culture, the blame-free nature of the program, and the availability of
      electronic health information. The Outpatient Safety Net Program framework may be
      adopted by other organizations, including those who have electronic health
      information but not an electronic health record. In the future, the creation of a
      forum to share electronic clinical surveillance programs across organizations may
      facilitate more rapid improvements in outpatient safety. 

PMID- 25848589
TI  - Data governance and data sharing agreements for community-wide health information
      exchange: lessons from the beacon communities.
AB  - PURPOSE: Unprecedented efforts are underway across the United States to
      electronically capture and exchange health information to improve health care and
      population health, and reduce costs. This increased collection and sharing of
      electronic patient data raises several governance issues, including privacy,
      security, liability, and market competition. Those engaged in such efforts have
      had to develop data sharing agreements (DSAs) among entities involved in
      information exchange, many of whom are "nontraditional" health care entities
      and/or new partners. This paper shares lessons learned based on the experiences
      of six federally funded communities participating in the Beacon Community
      Cooperative Agreement Program, and offers guidance for navigating data governance
      issues and developing DSAs to facilitate community-wide health information
      exchange. INNOVATION: While all entities involved in electronic data sharing must
      address governance issues and create DSAs accordingly, until recently little
      formal guidance existed for doing so - particularly for community-based
      initiatives. Despite this lack of guidance, together the Beacon Communities'
      experiences highlight promising strategies for navigating complex governance
      issues, which may be useful to other entities or communities initiating
      information exchange efforts to support delivery system transformation.
      CREDIBILITY: For the past three years, AcademyHealth has provided technical
      assistance to most of the 17 Beacon Communities, 6 of whom contributed to this
      collaborative writing effort. Though these communities varied widely in terms of
      their demographics, resources, and Beacon-driven priorities, common themes
      emerged as they described their approaches to data governance and DSA
      development. CONCLUSIONS: The 6 Beacon Communities confirmed that DSAs are
      necessary to satisfy legal and market-based concerns, and they identified several
      specific issues, many of which have been noted by others involved in network data
      sharing initiatives. More importantly, these communities identified several
      promising approaches to timely and effective DSA development, including:
      stakeholder engagement; identification and effective communication of value;
      adoption of a parsimonious approach; attention to market-based concerns;
      flexibility in adapting and expanding existing agreements and partnerships; and
      anticipation of required time and investment.

PMID- 25848590
TI  - The COMET Sleep Research Platform.
AB  - INTRODUCTION: The Comparative Outcomes Management with Electronic Data Technology
      (COMET) platform is extensible and designed for facilitating multicenter
      electronic clinical research. BACKGROUND: Our research goals were the following:
      (1) to conduct a comparative effectiveness trial (CET) for two obstructive sleep
      apnea treatments-positive airway pressure versus oral appliance therapy; and (2)
      to establish a new electronic network infrastructure that would support this
      study and other clinical research studies. DISCUSSION: The COMET platform was
      created to satisfy the needs of CET with a focus on creating a platform that
      provides comprehensive toolsets, multisite collaboration, and end-to-end data
      management. The platform also provides medical researchers the ability to
      visualize and interpret data using business intelligence (BI) tools. CONCLUSION:
      COMET is a research platform that is scalable and extensible, and which, in a
      future version, can accommodate big data sets and enable efficient and effective
      research across multiple studies and medical specialties. The COMET platform
      components were designed for an eventual move to a cloud computing infrastructure
      that enhances sustainability, overall cost effectiveness, and return on
      investment.

PMID- 25848591
TI  - Learning from health information exchange technical architecture and
      implementation in seven beacon communities.
AB  - As health care providers adopt and make "meaningful use" of health information
      technology (health IT), communities and delivery systems must set up the
      infrastructure to facilitate health information exchange (HIE) between providers
      and numerous other stakeholders who have a role in supporting health and care. By
      facilitating better communication and coordination between providers, HIE has the
      potential to improve clinical decision-making and continuity of care, while
      reducing unnecessary use of services. When implemented as part of a broader
      strategy for health care delivery system and payment reform, HIE capability also
      can enable the use of analytic tools needed for population health management,
      patient engagement in care, and continuous learning and improvement. The diverse
      experiences of seven communities that participated in the three-year federal
      Beacon Community Program offer practical insight into factors influencing the
      technical architecture of exchange infrastructure and its role in supporting
      improved care, reduced cost, and a healthier population. The case studies also
      document challenges faced by the communities, such as significant time and
      resources required to harmonize variations in the interpretation of data
      standards. Findings indicate that their progress developing community-based HIE
      strategies, while driven by local needs and objectives, is also influenced by
      broader legal, policy, and market conditions. 

PMID- 25848592
TI  - Importance of the medicaid medical directors' multistate collaborative for
      improving care in medicaid.
AB  - INTRODUCTION: There are many benefits of multistate collaboratives or networks to
      states, but at the center is that they allow for the opportunity to learn from
      other states and experts about the practices and policies states have implemented
      without the significant time lag of published research. This commentary examines
      these benefits and illustrates the importance of quality improvement
      collaborations to decision-making in state Medicaid programs. BACKGROUND: In
      2007, the Medicaid Medical Directors Learning Network (MMDLN) began conducting
      quality improvement studies using their own state-level administrative data to
      better understand the major clinical issues facing the Medicaid populations and
      to work together on policies to improve outcomes. RATIONALE AND RESULTS: The
      three issues selected by MMDs for quality improvement monitoring to date involved
      an important national problem - including both morbidity and cost - and were
      amenable to policy solutions. The studies examined the use of antipsychotic
      medication in children, hospital admissions and readmissions, and early elective
      deliveries (i.e., elective deliveries occurring before 39 weeks). IMPORTANCE AND
      UTILITY: The multistate clinical quality projects conducted offer a key mechanism
      for achieving the goal of helping the Medicaid program deliver value-driven, high
      quality, cost-effective health care in an efficient manner. These projects also
      provide the participating states with data to inform policies internally.
      CONCLUSIONS: In order for the quality of health care to improve, the system needs
      to be structured as a learning health care system; one that is always accessing
      evidence, implementing a variation of it (i.e., with new data sources or tools
      such as electronic clinical data), assessing effectiveness, and sharing results
      for others to repeat the cycle.

PMID- 25848593
TI  - Accelerating regulatory progress in multi-institutional research.
AB  - PURPOSE: Multi-institutional collaborations are necessary in order to create
      large and robust data sets that are needed to answer important comparative
      effectiveness research (CER) questions. Before scientific work can begin, a
      complex maze of administrative and regulatory requirements must be efficiently
      navigated to avoid project delays. INNOVATION: Staff from research, regulatory,
      and administrative teams involved in three HMO Research Network (HMORN) multi
      institutional collaborations developed and employed novel approaches: to secure
      and maintain Institutional Review Board (IRB) approvals; to enable data sharing,
      and to expedite subawards for two data-only minimal risk studies. These novel
      approaches accelerated required processes and approvals while maintaining
      regulatory, human subjects, and institutional protections. CREDIBILITY: Outcomes
      from the processes described here are compared with processes outlined in the
      research and regulatory literature and with processes that have been used in
      previous multisite research collaborations. CONCLUSION AND DISCUSSION: Research,
      regulatory, and administrative staff are essential contributors to the success of
      multi-institutional collaborations. Their flexibility, creativity, and effective
      communication skills can lead to the development of efficient approaches to
      achieving the necessary oversight for these complex projects. Elements of these
      specific strategies can be adapted and used by other research networks. Other
      efforts in these areas should be evaluated and shared. The processes that help
      develop a "learning research system" play an important and complementary role in
      sustaining multi-institutional research collaborations.

PMID- 25848594
TI  - Availability of structured and unstructured clinical data for comparative
      effectiveness research and quality improvement: a multisite assessment.
AB  - INTRODUCTION: A key attribute of a learning health care system is the ability to
      collect and analyze routinely collected clinical data in order to quickly
      generate new clinical evidence, and to monitor the quality of the care provided.
      To achieve this vision, clinical data must be easy to extract and stored in
      computer readable formats. We conducted this study across multiple organizations
      to assess the availability of such data specifically for comparative
      effectiveness research (CER) and quality improvement (QI) on surgical procedures.
      SETTING: This study was conducted in the context of the data needed for the
      already established Surgical Care and Outcomes Assessment Program (SCOAP), a
      clinician-led, performance benchmarking, and QI registry for surgical and
      interventional procedures in Washington State. METHODS: We selected six
      hospitals, managed by two Health Information Technology (HIT) groups, and
      assessed the ease of automated extraction of the data required to complete the
      SCOAP data collection forms. Each data element was classified as easy, moderate,
      or complex to extract. RESULTS: Overall, a significant proportion of the data
      required to automatically complete the SCOAP forms was not stored in structured
      computer-readable formats, with more than 75 percent of all data elements being
      classified as moderately complex or complex to extract. The distribution differed
      significantly between the health care systems studied. CONCLUSIONS: Although
      highly desirable, a learning health care system does not automatically emerge
      from the implementation of electronic health records (EHRs). Innovative methods
      to improve the structured capture of clinical data are needed to facilitate the
      use of routinely collected clinical data for patient phenotyping.

PMID- 25848595
TI  - The visit-data warehouse: enabling novel secondary use of health information
      exchange data.
AB  - INTRODUCTION/OBJECTIVES: Health Information Exchange (HIE) efforts face
      challenges with data quality and performance, and this becomes especially
      problematic when data is leveraged for uses beyond primary clinical use. We
      describe a secondary data infrastructure focusing on patient-encounter,
      nonclinical data that was built on top of a functioning HIE platform to support
      novel secondary data uses and prevent potentially negative impacts these uses
      might have otherwise had on HIE system performance. BACKGROUND: HIE efforts have
      generally formed for the primary clinical use of individual clinical providers
      searching for data on individual patients under their care, but many secondary
      uses have been proposed and are being piloted to support care management, quality
      improvement, and public health. DESCRIPTION OF THE HIE AND BASE INFRASTRUCTURE:
      This infrastructure review describes a module built into the Healthix HIE.
      Healthix, based in the New York metropolitan region, comprises 107 participating
      organizations with 29,946 acute-care beds in 383 facilities, and includes more
      than 9.2 million unique patients. The primary infrastructure is based on the
      InterSystems proprietary Cache data model distributed across servers in multiple
      locations, and uses a master patient index to link individual patients' records
      across multiple sites. We built a parallel platform, the "visit data warehouse,"
      of patient encounter data (demographics, date, time, and type of visit) using a
      relational database model to allow accessibility using standard database tools
      and flexibility for developing secondary data use cases. These four secondary use
      cases include the following: (1) tracking encounter-based metrics in a newly
      established geriatric emergency department (ED), (2) creating a dashboard to
      provide a visual display as well as a tabular output of near-real-time de
      identified encounter data from the data warehouse, (3) tracking frequent ED users
      as part of a regional-approach to case management intervention, and (4) improving
      an existing quality improvement program that analyzes patients with return visits
      to EDs within 72 hours of discharge. RESULTS/LESSONS LEARNED: Setting up a
      separate, near-real-time, encounters-based relational database to complement an
      HIE built on a hierarchical database is feasible, and may be necessary to support
      many secondary uses of HIE data. As of November 2014, the visit-data warehouse
      (VDW) built by Healthix is undergoing technical validation testing and updates on
      an hourly basis. We had to address data integrity issues with both nonstandard
      and missing HL7 messages because of varied HL7 implementation across the HIE.
      Also, given our HIEs federated structure, some sites expressed concerns regarding
      data centralization for the VDW. An established and stable HIE governance
      structure was critical in overcoming this initial reluctance. CONCLUSIONS: As
      secondary use of HIE data becomes more prevalent, it may be increasingly
      necessary to build separate infrastructure to support secondary use without
      compromising performance. More research is needed to determine optimal ways of
      building such infrastructure and validating its use for secondary purposes.

PMID- 25848596
TI  - Patient report improves posthospital discharge event capture in total joint
      replacement: a novel approach to capturing all posthospital event data.
AB  - INTRODUCTION: Current approaches to quantifying total posthospital complications
      and readmissions following surgical procedures are limited because the United
      States does not have a single health care payer. Patients seek posthospital care
      in varied locations, yet hospitals can only quantify those returning to the same
      facility. Seeking information directly from patients about health care
      utilization following hospital discharge holds promise to provide data that is
      missing for surgeons and health care systems. BACKGROUND: Because total joint
      replacement (TJR) is the most common and costly elective surgical
      hospitalization, we examined the concordance between patients' self-report of
      potential short-term complications and their readmissions and our review of
      medical records in the initial hospital and surrounding facilities. METHODS:
      Patients undergoing primary total hip or knee replacement from July 1, 2011,
      through December 3, 2012, at a large site participating in a national cohort of
      TJR patients were identified. Patients completed a six-month postoperative survey
      regarding emergency department (ED), day surgery (DS), or inpatient care for
      possible medical or mechanical post-TJR complications. We reviewed inpatient and
      outpatient medical records from all regional facilities and examined the
      sensitivity, specificity, and positive- and negative predictive values for
      patient self-report and medical records. FINDINGS: There were 413 patients who
      had 431 surgeries and completed the six-month questionnaire. Patients reported 40
      medical encounters (9 percent) including ED, DS or inpatient care, of which 20
      percent occurred at hospitals different from the initial surgery. Review of
      medical records revealed 9 additional medical encounters that patients had not
      mentioned including five hospitalizations following surgery and four ED visits.
      Overall patient self-report of ED, DS, and inpatient care for possible
      complications was both sensitive (82 percent) and specific (100 percent). The
      positive predictive value was 100 percent and negative predictive value 98
      percent. DISCUSSION: Patient self-report of posthospital events was accurate.
      Substantial numbers of patients required care at outlying hospitals (not where
      the TJR occurred). CONCLUSION: Methods that directly engage patients can augment
      current posthospital utilization surveillance to assure complete data.

PMID- 25848597
TI  - Transforming the Premier Perspective Hospital Database into the Observational
      Medical Outcomes Partnership (OMOP) Common Data Model.
AB  - BACKGROUND: The Observational Medical Outcomes Partnership (OMOP) Common Data
      Model (CDM) has been implemented on various claims and electronic health record
      (EHR) databases, but has not been applied to a hospital transactional database.
      This study addresses the implementation of the OMOP CDM on the U.S. Premier
      Hospital database. METHODS: We designed and implemented an extract, transform,
      load (ETL) process to convert the Premier hospital database into the OMOP CDM.
      Standard charge codes in Premier were mapped between the OMOP version 4.0
      Vocabulary and standard charge descriptions. Visit logic was added to impute the
      visit dates. We tested the conversion by replicating a published study using the
      raw and transformed databases. The Premier hospital database was compared to a
      claims database, in regard to prevalence of disease. FINDINGS: The data
      transformed into the CDM resulted in 1% of the data being discarded due to data
      errors in the raw data. A total of 91.4% of Premier standard charge codes were
      mapped successfully to a standard vocabulary. The results of the replication
      study resulted in a similar distribution of patient characteristics. The
      comparison to the claims data yields notable similarities and differences amongst
      conditions represented in both databases. DISCUSSION: The transformation of the
      Premier database into the OMOP CDM version 4.0 adds value in conducting analyses
      due to successful mapping of the drugs and procedures. The addition of visit
      logic gives ordinality to drugs and procedures that wasn't present prior to the
      transformation. Comparing conditions in Premier against a claims database can
      provide an understanding about Premier's potential use in pharmacoepidemiology
      studies that are traditionally conducted via claims databases. CONCLUSION AND
      NEXT STEPS: The conversion of the Premier database into the OMOP CDM 4.0 was
      completed successfully. The next steps include refinement of vocabularies and
      mappings and continual maintenance of the transformed CDM.

PMID- 25848598
TI  - Automating data abstraction in a quality improvement platform for surgical and
      interventional procedures.
AB  - OBJECTIVE: This paper describes a text processing system designed to automate the
      manual data abstraction process in a quality improvement (QI) program. The
      Surgical Care and Outcomes Assessment Program (SCOAP) is a clinician-led,
      statewide performance benchmarking QI platform for surgical and interventional
      procedures. The data elements abstracted as part of this program cover a wide
      range of clinical information from patient medical history to details of surgical
      interventions. METHODS: Statistical and rule-based extractors were developed to
      automatically abstract data elements. A preprocessing pipeline was created to
      chunk free-text notes into its sections, sentences, and tokens. The information
      extracted in this preprocessing step was used by the statistical and rule-based
      extractors as features. FINDINGS: Performance results for 25 extractors (14
      statistical, 11 rule based) are presented. The average f1-scores for 11 rule
      based extractors and 14 statistical extractors are 0.785 (min=0.576,max=0.931,std
      dev=0.113) and 0.812 (min=0.571,max=0.993,std-dev=0.135) respectively.
      DISCUSSION: Our error analysis revealed that most extraction errors were due
      either to data imbalance in the data set or the way the gold standard had been
      created. CONCLUSION: As future work, more experiments will be conducted with a
      more comprehensive data set from multiple institutions contributing to the QI
      project.

PMID- 25848599
TI  - Modifying the electronic health record to facilitate the implementation and
      evaluation of a bundled care program for intensive care unit delirium.
AB  - CONTEXT: Electronic health records (EHRs) have been promoted as a key driver of
      improved patient care and outcomes and as an essential component of learning
      health systems. However, to date, many EHRs are not optimized to support delivery
      of quality and safety initiatives, particularly in Intensive Care Units (ICUs).
      Delirium is a common and severe problem for ICU patients that may be prevented or
      mitigated through the use of evidence-based care processes (daily awakening and
      breathing trials, formal delirium screening, and early mobility-collectively
      known as the "ABCDE bundle"). This case study describes how an integrated health
      care delivery system modified its inpatient EHR to accelerate the implementation
      and evaluation of ABCDE bundle deployment as a safety and quality initiative.
      CASE DESCRIPTION: In order to facilitate uptake of the ABCDE bundle and measure
      delivery of the care processes within the bundle, we worked with clinical and
      technical experts to create structured data fields for documentation of bundle
      elements and to identify where these fields should be placed within the EHR to
      streamline staff workflow. We created an "ABCDE" tab in the existing patient
      viewer that allowed providers to easily identify which components of the bundle
      the patient had and had not received. We examined the percentage of ABCDE bundle
      elements captured in these structured data fields over time to track compliance
      with data entry procedures and to improve documentation of care processes. MAJOR
      THEMES: Modifying the EHR to support ABCDE bundle deployment was a complex and
      time-consuming process. We found that it was critical to gain buy-in from senior
      leadership on the importance of the ABCDE bundle to secure information technology
      (IT) resources, understand the different workflows of members of
      multidisciplinary care teams, and obtain continuous feedback from staff on the
      EHR revisions during the development cycle. We also observed that it was
      essential to provide ongoing training to staff on proper use of the new EHR
      documentation fields. Lastly, timely reporting on ABCDE bundle performance may be
      essential to improved practice adoption and documentation of care processes.
      CONCLUSION: The creation of learning health systems is contingent on an ability
      to modify EHRs to meet emerging care delivery and quality improvement needs.
      Although this study focuses on the prevention and mitigation of delirium in ICUs,
      our process for identifying key data elements and making modifications to the
      EHR, as well as the lessons learned from the IT components of this program, are
      generalizable to other health care settings and conditions.

PMID- 25848600
TI  - Developing electronic data methods infrastructure to participate in collaborative
      research networks.
AB  - CONTEXT: Collaborative networks support the goals of a learning health system by
      sharing, aggregating, and analyzing data to facilitate identification of best
      practices care across delivery organizations. This case study describes the
      infrastructure and process developed by an integrated health delivery system to
      successfully prepare and submit a complex data set to a large national
      collaborative network. CASE DESCRIPTION: We submitted four years of data for a
      diverse population of patients in specific clinical areas: diabetes, chronic
      heart failure, sepsis, and hip, knee, and spine. The most recent submission
      included 19 tables, more than 376,000 unique patients, and almost 5 million
      patient encounters. Data was extracted from multiple clinical and administrative
      systems. LESSONS LEARNED: We found that a structured process with documentation
      was key to maintaining communication, timelines, and quality in a large-scale
      data submission to a national collaborative network. The three key components of
      this process were the experienced project team, documentation, and communication.
      We used a formal QA and feedback process to track and review data. Overall, the
      data submission was resource intensive and required an incremental approach to
      data quality. CONCLUSION: Participation in collaborative networks can be time and
      resource intense, however it can serve as a catalyst to increase the technical
      data available to the learning health system.

PMID- 25848601
TI  - Web-based Comparative Patient-reported Outcome Feedback to Support Quality
      Improvement and Comparative Effectiveness Research in Total Joint Replacement.
AB  - INTRODUCTION: Patient-reported outcomes (PROs) are rarely included in quality
      monitoring systems, surgeon comparative feedback reports, or registries. We
      present the design and implementation of a secure website in a federally funded
      research program-Function and Outcomes Research for Comparative Effectiveness in
      Total Joint Replacement (FORCE-TJR)-to return comparative PRO reports to
      participating surgeons, in addition to including traditional quality measures, in
      order to monitor and improve quality and health outcomes. METHODS: The surgeon
      specific comparative PRO reports were designed and structured based on user input
      for content, data elements, integration, and display. Three questions are
      addressed regarding the knee and hip joint symptom profiles of patients before
      TJR, as well as outcomes of surgery. The website is organized with a hierarchical
      structure to display data at national, practice, and individual surgeon levels,
      and provides a comprehensive site-level executive summary and surgeon-level data
      reports that can be downloaded. EARLY RESULTS: As of September 2014, over 22,000
      patients were enrolled from more than 130 surgeons in 22 states. The reporting
      website was launched in September 2012 and has been updated quarterly for all
      surgeons to review their site- and individual-specific outcomes data compared to
      national benchmarks. DISCUSSION: In this novel system, quarterly comparative
      surgeon feedback extends beyond traditional measures of complication rates to
      include PROs of pain relief and functional gain. We anticipate that this enhanced
      data will facilitate patient-centered quality improvement (QI) and outcomes
      research from the registry. As the Centers for Medicare & Medicaid Services (CMS)
      and other insurers consider future implementation of PROs, surgeons will
      increasingly need comparative data by which to self-monitor their practice
      outcomes.

PMID- 25848602
TI  - eGEMs' Early Adventures in Open Access Publishing.
AB  - INTRODUCTION: In January 2013 AcademyHealth officially launched eGEMs (Generating
      Evidence and Methods to improve patient outcomes) to rapidly disseminate peer
      reviewed approaches using electronic health data (EHD) to advance research and
      quality improvement (QI), with the overall goal of improving patient and
      community outcomes. Inspired by the publication of eGEMs 50(th) paper, Dr. Erin
      Holve, eGEMs editor-in-chief reviews the EDM Forum's early experiences with open
      access publishing. EGEMS TO DATE: As of the end of September 2014 eGEMs has
      published 59 manuscripts and received nearly 150 submissions. These early
      findings demonstrate eGEMs is filling a need for dissemination outlets that
      bridge the gap between the health research and practice communities. Published
      papers are distributed across the EDM Forum's four thematic domains: governance
      (n=5), informatics (n=14), methods (n=13) and learning health systems (n=27).
      While system design issues are a consistent theme, papers addressing priority
      health topics such as diabetes, asthma, and obesity are frequently submitted.
      Authors include more than two hundred experts in the field representing nearly
      all of the EDM Forum's core stakeholder groups: research/QI, nonprofit/policy,
      healthcare delivery, government, industry, and patients/consumers. WHAT'S NEXT:
      With the help of our diverse community, eGEMs will continue to expand its depth
      and reach. Forthcoming special issues on community-level transformation using
      health IT, and ways to improve user-experience and system design will add to the
      journal's robust portfolio of work identifying and addressing shared challenges
      using EHD. The EDM Forum, working closely with our partners at the Agency for
      Healthcare Research and Quality, will work diligently to ensure eGEMs is
      accelerating the pace at which the community translates and disseminates key
      lessons, with the ultimate goal of helping transform knowledge into actions that
      can improve health and health care.

PMID- 25848603
TI  - The DARTNet Institute: Seeking a Sustainable Support Mechanism for Electronic
      Data Enabled Research Networks.
AB  - CONTEXT: Clinical data research networks require large investments in
      infrastructure support to maintain their abilities to extract, transform, and
      load data from varied data sources, expand electronic data sources and develop
      learning communities. CASE DESCRIPTION: This paper outlines a sustainable
      business model of ongoing infrastructure support for clinical data research
      activities. The DARTNet Institute is a not-for-profit 501(c)(3) organization that
      serves as a support entity for multiple practice-based research networks. Several
      clinical data research networks working closely with a professional society began
      collaborating to support shared goals in 2008. This loose affiliation called
      itself the "DARTNet Collaborative." In 2011, the DARTNet Institute incorporated
      as an independent, not-for-profit entity. The business structure allows DARTNet
      to advocate for all partners without operating its own practice-based research
      network, serve as a legal voice for activities that overlap multiple partners,
      share personnel resources through service contracts between partners, and
      purchase low-cost (nonprofit rate) software. MAJOR THEMES: DARTNet's business
      model relies upon four diverse sources of revenue: (1) DARTNet licenses and
      provides access to a propriety software system that extracts, transforms, and
      loads data from all major electronic health records (EHRs) utilized in the United
      States, and which also provides clinical decision support for research studies;
      (2) DARTNet operates a recognized, national professional-society-quality
      improvement registry that enables organizations to fulfill Meaningful Use 2
      criteria; (3) DARTNet provides access to data for research activities that are
      funded by direct research dollars, provided at prices that generate excess
      revenue; and (4) DARTNet provides access to large primary care datasets for
      observational studies and pregrant analyses such as for sample size development.
      The ability of the system to support pragmatic trials will be described.
      CONCLUSION: The DARTNet model facilitates the use of direct grant dollars to
      generate revenue to support the overall enterprise through a purchased services
      arrangement. Other services provided through subcontracting provide facilities
      and administration fees as well as direct dollars to support the system. The
      flexibility of the business model overcomes the complicated financial
      arrangements and governance requirements of many professional associations and
      academic medical centers.

PMID- 25848604
TI  - State synergies and disease surveillance: creating an electronic health data
      communication model for cancer reporting and comparative effectiveness research
      in kentucky.
AB  - PURPOSE: This case study describes the collaboration between a state public
      health department, a major research university, and a health extension service
      funded as part of the Health Information Technology for Economic and Clinical
      Health (HITECH) Act to establish an interoperable health information system for
      disease surveillance through electronic reporting of systemic therapy data from
      numerous oncology practices in Kentucky. The experience of the Kentucky cancer
      surveillance system can help local and state entities achieve greater
      effectiveness in designing communication efforts to increase usage of electronic
      health records (EHRs) and health information exchanges (HIEs), help eligible
      clinicians meet these new standards in patient care, and conduct disease
      surveillance in a learning health system. INNOVATION: We document and assess the
      statewide efforts of early health information technology (HIT) adopters in
      Kentucky to facilitate the nation's first electronic transmission of a clinical
      document architecture (CDA) from a physician office to a state cancer
      surveillance registry in November 2012. Successful transmission of the CDA not
      only represented a landmark for technology innovators, informaticists, and
      clinicians, but it also set in motion a new communication mechanism by which
      state and federal agencies can capture and trade vital cancer statistics in a way
      that is safe, secure, and timely. The corresponding impact this has on cancer
      surveillance and comparative effective research is immense. With guidance from
      the Centers for Disease Control and Prevention (CDC), the Kentucky Cancer
      Registry (KCR), the Kentucky Health Information Exchange (KHIE), and the Kentucky
      Regional Extension Center (KREC) have moved one step further in transforming the
      interoperable health environment for improved disease surveillance. CREDIBILITY:
      This case study describes the efforts of established and reputable agencies,
      including the KCR, the state department of health, state and federal governmental
      agencies, and a major research university in leveraging existing networks,
      infrastructure, and federally awarded funding to implement interoperable health
      information systems for disease surveillance. Project assessment through quasi
      qualitative interviews with key stakeholders facilitated evaluation of attitudes
      and beliefs for continued use of the cancer surveillance model. CONCLUSION AND
      DISCUSSION: In Kentucky, the cancer reporting initiative leveraged and enhanced a
      solid foundation for statewide collaboration to achieve better health and
      improved disease surveillance through a learning health system. Leveraging the
      Meaningful Use (MU) program as an overarching policy and structural driver is
      imperative. The cancer reporting initiative in Kentucky suggests that future
      surveillance and reporting initiatives will require locally adaptable solutions
      and that there is a need for increased technical assistance in rural settings.
      Kentucky's experience also indicates that stakeholders should be diligent in
      identifying state-level criteria that align with MU for vetting EHR vendors.

PMID- 25848606
TI  - Achieving and sustaining automated health data linkages for learning systems:
      barriers and solutions.
AB  - INTRODUCTION: Delivering more appropriate, safer, and highly effective health
      care is the goal of a learning health care system. The Agency for Healthcare
      Research and Quality (AHRQ) funded enhanced registry projects: (1) to create and
      analyze valid data for comparative effectiveness research (CER); and (2) to
      enhance the ability to monitor and advance clinical quality improvement (QI).
      This case report describes barriers and solutions from one state-wide enhanced
      registry project. METHODS: The Comparative Effectiveness Research and Translation
      Network (CERTAIN) deployed the commercially available Amalga Unified Intelligence
      SystemTM (Amalga) as a central data repository to enhance an existing QI registry
      (the Automation Project). An eight-step implementation process included hospital
      recruitment, technical electronic health record (EHR) review, hospital-specific
      interface planning, data ingestion, and validation. Data ownership and security
      protocols were established, along with formal methods to separate data management
      for QI purposes and research purposes. Sustainability would come from lowered
      chart review costs and the hospital's desire to invest in the infrastructure
      after trying it. FINDINGS: CERTAIN approached 19 hospitals in Washington State
      operating within 12 unaffiliated health care systems for the Automation Project.
      Five of the 19 completed all implementation steps. Four hospitals did not
      participate due to lack of perceived institutional value. Ten hospitals did not
      participate because their information technology (IT) departments were
      oversubscribed (e.g., too busy with Meaningful Use upgrades). One organization
      representing 22 additional hospitals expressed interest, but was unable to
      overcome data governance barriers in time. Questions about data use for QI versus
      research were resolved in a widely adopted project framework. Hospitals
      restricted data delivery to a subset of patients, introducing substantial
      technical challenges. Overcoming challenges of idiosyncratic EHR implementations
      required each hospital to devote more IT resources than were predicted. Cost
      savings did not meet projections because of the increased IT resource
      requirements and a different source of lowered chart review costs. DISCUSSION:
      CERTAIN succeeded in recruiting unaffiliated hospitals into the Automation
      Project to create an enhanced registry to achieve AHRQ goals. This case report
      describes several distinct barriers to central data aggregation for QI and CER
      across unaffiliated hospitals: (1) competition for limited on-site IT expertise,
      (2) concerns about data use for QI versus research, (3) restrictions on data
      automation to a defined subset of patients, and (4) unpredictable resource needs
      because of idiosyncrasies among unaffiliated hospitals in how EHR data are coded,
      stored, and made available for transmission-even between hospitals using the same
      vendor's EHR. Therefore, even a fully optimized automation infrastructure would
      still not achieve complete automation. The Automation Project was unable to align
      sufficiently with internal hospital objectives, so it could not show a compelling
      case for sustainability.

PMID- 25848605
TI  - Sustaining Research Networks: the Twenty-Year Experience of the HMO Research
      Network.
AB  - PURPOSE: As multi-institutional research networks assume a central role in
      clinical research, they must address the challenge of sustainability. Despite its
      importance, the concept of network sustainability has received little attention
      in the literature, and the sustainability strategies of durable scientific
      networks have not been described. INNOVATION: The Health Maintenance Organization
      Research Network (HMORN) is a consortium of 18 research departments in integrated
      health care delivery systems with over 15 million members in the United States
      and Israel. The HMORN has coordinated federally funded scientific networks and
      studies since 1994. This case study describes the HMORN approach to
      sustainability, proposes an operational definition of network sustainability, and
      identifies 10 essential elements that can enhance sustainability. CREDIBILITY:
      The sustainability framework proposed here is drawn from prior publications on
      organizational issues by HMORN investigators and from the experience of recent
      HMORN leaders and senior staff. CONCLUSION AND DISCUSSION: Network sustainability
      can be defined as (1) the development and enhancement of shared research assets
      to facilitate a sequence of research studies in a specific content area or
      multiple areas, and (2) a community of researchers and other stakeholders who
      reuse and develop those assets. Essential elements needed to develop the shared
      assets of a network include: network governance; trustworthy data and processes
      for sharing data; shared knowledge about research tools; administrative
      efficiency; physical infrastructure; and infrastructure funding. The community of
      researchers within a network is enhanced by: a clearly defined mission, vision
      and values; protection of human subjects; a culture of collaboration; and strong
      relationships with host organizations. While the importance of these elements
      varies based on the membership and goals of a network, this framework for
      sustainability can enhance strategic planning within the network and can guide
      relationships with external stakeholders.

PMID- 25848607
TI  - The national anesthesia clinical outcomes registry: a sustainable model for the
      information age?
AB  - Anesthesiologists care for patients of all ages, with all conceivable
      comorbidities, in every kind of health care facility. This leads to a significant
      challenge in the collection of data to describe the specialty, and in the
      development of evidence-based performance measures for anesthesiologists. Whereas
      narrowly defined medical specialties have developed registries based on manual
      abstraction of clinical data from the medical record (e.g., cardiac surgery),
      this approach would be prohibitively expensive for anesthesiology, and is
      unlikely to generate statistically useful data when major adverse outcomes occur
      a handful of times in tens of thousands of cases. The American Society of
      Anesthesiologists (ASA) addressed this challenge in 2008 by funding a related
      organization, the Anesthesia Quality Institute (AQI), to develop the National
      Anesthesia Clinical Outcomes Registry (NACOR). The technical development of this
      registry and the approach taken to define the specialty of anesthesiology and the
      performance of anesthesiologists may serve as a model for other specialty society
      efforts. 

PMID- 25848608
TI  - Mission and Sustainability of Informatics for Integrating Biology and the Bedside
      (i2b2).
AB  - INTRODUCTION: A visible example of a successfully disseminated research project
      in the healthcare space is Informatics for Integrating Biology and the Bedside,
      or i2b2. The project serves to provide the software that can allow a researcher
      to do direct, self-serve queries against the electronic healthcare data form a
      hospital. The goals of these queries are to find cohorts of patients that fit
      specific profiles, while providing for patient privacy and discretion. Sustaining
      this resource and keeping its direction has always been a challenge, but ever
      more so as the ten year National Centers for Biomedical Computing (NCBCs) sunset
      their funding. FINDINGS: Building on the i2b2 structures has helped the
      dissemination plans for grants leveraging it because it is a disseminated
      national resource. While this has not directly increased the support of i2b2
      internally, it has increased the ability of institutions to leverage the resource
      and generally leads to increased institutional support. DISCUSSION: The
      successful development, use, and dissemination i2b2 has been significant in
      clinical research and informatics. Its evolution has been from a local research
      data infrastructure to one disseminated more broadly than any other product of
      the National Centers for Biomedical Computing, and an infrastructure spawning
      larger investments than were originally used to create it. Throughout this, there
      were two main lessons about the benefits of dissemination: that people have great
      creativity in utilizing a resource in different ways and that broader system use
      can make the system more robust. One option for long-term sustainability of the
      central authority would be to translate the function to an industry partner.
      Another option currently being pursued is to create a foundation that would be a
      central authority for the project. CONCLUSION: Over the past 10 years, i2b2 has
      risen to be an important staple in the toolkit of health care researchers. There
      are now over 110 hospitals that use i2b2 for research. This open-source platform
      has a community of developers that are continuously enhancing the analytic
      capacities of the platform and inventing new functionality. By understanding how
      i2b2 has been sustained, we hope that other research infrastructure projects may
      better navigate options in making those initiatives sustainable over time.

PMID- 25848609
TI  - Sustainability Through Technology Licensing and Commercialization: Lessons
      Learned from the TRIAD Project.
AB  - Ongoing transformation relative to the funding climate for healthcare research
      programs housed in academic and non-profit research organizations has led to a
      new (or renewed) emphasis on the pursuit of non-traditional sustainability
      models. This need is often particularly acute in the context of data management
      and sharing infrastructure that is developed under the auspices of such research
      initiatives. One option for achieving sustainability of such data management and
      sharing infrastructure is the pursuit of technology licensing and
      commercialization, in an effort to establish public-private or equivalent
      partnerships that sustain and even expand upon the development and dissemination
      of research-oriented data management and sharing technologies. However, the
      critical success factors for technology licensing and commercialization efforts
      are often unknown to individuals outside of the private sector, thus making this
      type of endeavor challenging to investigators in academic and non-profit
      settings. In response to such a gap in knowledge, this article will review a
      number of generalizable lessons learned from an effort undertaken at The Ohio
      State University to commercialize a prototypical research-oriented data
      management and sharing infrastructure, known as the Translational Research
      Informatics and Data Management (TRIAD) Grid. It is important to note that the
      specific emphasis of these lessons learned is on the early stages of moving a
      technology from the research setting into a private-sector entity and as such are
      particularly relevant to academic investigators interested in pursuing such
      activities. 

PMID- 25848610
TI  - Sustainability considerations for health research and analytic data
      infrastructures.
AB  - INTRODUCTION: The United States has made recent large investments in creating
      data infrastructures to support the important goals of patient-centered outcomes
      research (PCOR) and comparative effectiveness research (CER), with still more
      investment planned. These initial investments, while critical to the creation of
      the infrastructures, are not expected to sustain them much beyond the initial
      development. To provide the maximum benefit, the infrastructures need to be
      sustained through innovative financing models while providing value to PCOR and
      CER researchers. SUSTAINABILITY FACTORS: Based on our experience with creating
      flexible sustainability strategies (i.e., strategies that are adaptive to the
      different characteristics and opportunities of a resource or infrastructure), we
      define specific factors that are important considerations in developing a
      sustainability strategy. These factors include assets, expansion, complexity, and
      stakeholders. Each factor is described, with examples of how it is applied. These
      factors are dimensions of variation in different resources, to which a
      sustainability strategy should adapt. SUMMARY OBSERVATIONS: We also identify
      specific important considerations for maintaining an infrastructure, so that the
      long-term intended benefits can be realized. These observations are presented as
      lessons learned, to be applied to other sustainability efforts. We define the
      lessons learned, relating them to the defined sustainability factors as
      interactions between factors. CONCLUSION AND NEXT STEPS: Using perspectives and
      experiences from a diverse group of experts, we define broad characteristics of
      sustainability strategies and important observations, which can vary for
      different projects. Other descriptions of adaptive, flexible, and successful
      models of collaboration between stakeholders and data infrastructures can expand
      this framework by identifying other factors for sustainability, and give more
      concrete directions on how sustainability can be best achieved.

PMID- 25848611
TI  - Sustaining the effective use of health care data: a message from the editors.
AB  - INTRODUCTION: Over the past decade, several initiatives have funded large
      projects to develop clinical research data infrastructures totaling several
      hundred million dollars. While most of this funding has ended or is expected to
      end soon, the projects themselves must struggle to continue operations beyond the
      initial funding. Examples of sustained research-data infrastructures are lacking,
      and recommended approaches to improve sustainability of developing
      infrastructures are even rarer. Early on, the Electronic Data Methods (EDM) Forum
      and the Agency for Healthcare Research and Quality (AHRQ) as its sponsor
      recognized the need to study strategies for sustainability. THEMES: Three
      prominent themes relating to sustainability arise among the articles in this
      special issue: the importance of project maturity, commercialization activities,
      and stakeholder support. Maturity was relevant to all the papers since a
      project's maturity directly influences the opportunities that are available,
      while commercialization and stakeholder support emerged from comparisons among
      subsets of articles. NEXT STEPS: The papers in this issue create a useful initial
      set of case studies to help in understanding sustainability issues for data
      infrastructures needed for research and QI. Each paper includes important lessons
      learned from the authors' experience with the different projects that should
      resonate with the broader fields of clinical research and clinical research
      informatics. There is an ongoing need for greater understanding of sustainability
      beyond what this issue provides. As more case studies of sustainability are
      accumulated, it is expected even more important themes will emerge from
      qualitative reviews that can eventually be demonstrated quantitatively.

PMID- 25848612
TI  - The keys to governance and stakeholder engagement: the southeast michigan beacon
      community case study.
AB  - Community-based health information exchanges (HIEs) and efforts to consolidate
      and house data are growing, given the advent of Accountable Care Organizations
      (ACOs) under the Affordable Care Act and other similar population health focused
      initiatives. The Southeast Michigan Beacon Community (SEMBC) can be looked to as
      one case study that offers lessons learned, insights on challenges faced and
      accompanying workarounds related to governance and stakeholder engagement. The
      SEMBC case study employs an established Data Warehouse Governance Framework to
      identify and explain the necessary governance and stakeholder engagement
      components, particularly as they relate to community-wide data sharing and data
      warehouses or repositories. Perhaps the biggest lesson learned through the SEMBC
      experience is that community-based work is hard. It requires a great deal of
      community leadership, collaboration and resources. SEMBC found that
      organizational structure and guiding principles needed to be continually
      revisited and nurtured in order to build the relationships and trust needed among
      stakeholder organizations. SEMBC also found that risks and risk mitigation
      tactics presented challenges and opportunities at the outset and through the
      duration of the three year pilot period. Other communities across the country
      embarking on similar efforts need to consider realistic expectations about
      community data sharing infrastructures and the accompanying and necessary
      governance and stakeholder engagement fundamentals. 

PMID- 25848613
TI  - How a Beacon Community Program in New Orleans Helped Create a Better Health Care
      System by Building Relationships before Technology.
AB  - INTRODUCTION: In the aftermath of Hurricane Katrina, much of New Orleans'
      healthcare infrastructure was destroyed. Initial federal funding after the storm
      expanded primary care services and helped set up medical homes for New Orleans'
      large uninsured and underinsured population. Following that, the Beacon Community
      in New Orleans, charged with improving health care through the use of technology,
      decided the best way to accomplish those goals was to build community
      partnerships and introduce technology improvements based on their input and on
      their terms. The purpose of this paper is to describe how those partnerships were
      wrought, including the innovative use of a conceptual framework, and how they are
      being sustained; how different technologies were and are being introduced; and
      what the results have been so far. METHODS: Past successful community
      experiences, as well as a proven conceptual framework, were used to help
      establish community partnerships and governance structures, as well as to
      demonstrate their linkages. This paper represents a compilation of reports and
      information from key Beacon leaders, staff and providers and their firsthand
      experiences in setting up those structures, as well as their conclusions.
      RESULTS: The community partnerships proved extremely successful in not only
      devising successful ways to introduce new technology into healthcare settings,
      but in sustaining those changes by creating a governance structure that has
      enough fluidity to adapt to changing circumstances. CONCLUSIONS: Building and
      developing community partnerships takes time and effort; however, these
      relationships are necessary and essential to introducing and sustaining new
      technologies in a healthcare setting and should be a first step for any
      organization looking to accomplish such goals.

PMID- 25848614
TI  - How patients can improve the accuracy of their medical records.
AB  - OBJECTIVES: Assess (1) if patients can improve their medical records' accuracy if
      effectively engaged using a networked Personal Health Record; (2) workflow
      efficiency and reliability for receiving and processing patient feedback; and (3)
      patient feedback's impact on medical record accuracy. BACKGROUND: Improving
      medical record' accuracy and associated challenges have been documented
      extensively. Providing patients with useful access to their records through
      information technology gives them new opportunities to improve their records'
      accuracy and completeness. A new approach supporting online contributions to
      their medication lists by patients of Geisinger Health Systems, an online patient
      engagement advocate, revealed this can be done successfully. In late 2011,
      Geisinger launched an online process for patients to provide electronic feedback
      on their medication lists' accuracy before a doctor visit. Patient feedback was
      routed to a Geisinger pharmacist, who reviewed it and followed up with the
      patient before changing the medication list shared by the patient and the
      clinicians. METHODS: The evaluation employed mixed methods and consisted of
      patient focus groups (users, nonusers, and partial users of the feedback form),
      semi structured interviews with providers and pharmacists, user observations with
      patients, and quantitative analysis of patient feedback data and pharmacists'
      medication reconciliation logs. FINDINGS/DISCUSSION: (1) Patients were eager to
      provide feedback on their medications and saw numerous advantages. Thirty percent
      of patient feedback forms (457 of 1,500) were completed and submitted to
      Geisinger. Patients requested changes to the shared medication lists in 89
      percent of cases (369 of 414 forms). These included frequency-or dosage changes
      to existing prescriptions and requests for new medications (prescriptions and
      over-the counter). (2) Patients provided useful and accurate online feedback. In
      a subsample of 107 forms, pharmacists responded positively to 68 percent of
      patient requests for medication list changes. (3) Processing patient feedback
      will requires both software algorithms and human interpretation. For the 107
      forms subsample, pharmacists accepted patient input in 51 percent of cases where
      they could not contact the patient. Where the patient was contacted, they
      accepted feedback from 68 percent. This suggests there may be opportunities to
      automate feedback filtering and processing for more efficient (and larger scale)
      medication-list optimization. (4) A supportive overall e-health environment makes
      acceptance of an online patient feedback system more likely. Review of Geisinger
      usage data showed patients who completed the medication feedback form had
      previously accessed MyGeisinger 2.3 times as often as the average patient and
      initiated secure messages with a clinician 1.35 times as often as patients not
      involved in the pilot. CONCLUSIONS: Patient feedback, placed in a useful
      workflow, can improve medical record accuracy. Electronic health record (EHR)
      vendors and developers need to build appropriate capabilities into applications.
      Continued research and development is needed for enabling health care
      organizations to elicit and process patient information most effectively.

PMID- 25848615
TI  - Leveraging health information exchange to improve population health reporting
      processes: lessons in using a collaborative-participatory design process.
AB  - INTRODUCTION: Surveillance, or the systematic monitoring of disease within a
      population, is a cornerstone function of public health. Despite significant
      investment in information technologies (IT) to improve the public's health,
      health care providers continue to rely on manual, spontaneous reporting processes
      that can result in incomplete and delayed surveillance activities. BACKGROUND:
      Participatory design principles advocate including real users and stakeholders
      when designing an information system to ensure high ecological validity of the
      product, incorporate relevance and context into the design, reduce misconceptions
      designers can make due to insufficient domain expertise, and ultimately reduce
      barriers to adoption of the system. This paper focuses on the collaborative and
      informal participatory design process used to develop enhanced, IT-enabled
      reporting processes that leverage available electronic health records in a health
      information exchange to prepopulate notifiable-conditions report forms used by
      public health authorities. METHODS: Over nine months, public health stakeholders,
      technical staff, and informatics researchers were engaged in a multiphase
      participatory design process that included public health stakeholder focus
      groups, investigator-engineering team meetings, public health survey and census
      regarding high-priority data elements, and codesign of exploratory prototypes and
      final form mock-ups. FINDINGS: A number of state-mandated report fields that are
      not highly used or desirable for disease investigation were eliminated, which
      allowed engineers to repurpose form space for desired and high-priority data
      elements and improve the usability of the forms. Our participatory design process
      ensured that IT development was driven by end user expertise and needs, resulting
      in significant improvements to the layout and functionality of the reporting
      forms. DISCUSSION: In addition to informing report form development, engaging
      with public health end users and stakeholders through the participatory design
      process provided new insights into public health workflow and allowed the team to
      quickly triage user requests while managing user expectations within the realm of
      engineering possibilities. CONCLUSION: Engaging public health, engineering staff,
      and investigators in a shared codesigning process ensured that the new forms will
      not only meet real-life needs but will also support development of a product that
      will be adopted and, ultimately, improve communicable and infectious disease
      reporting by clinicians to public health.

PMID- 25848616
TI  - Developing a communitywide electronic health record disease registry in primary
      care practices: lessons learned from the Western new york beacon community.
AB  - BACKGROUND AND INTRODUCTION: Disease registries, as part of electronic health
      records (EHRs), have shown promise in improving care and outcomes. However,
      little is known about how best to implement them across communities, especially
      in communities that are not highly integrated. The Western New York (WNY) primary
      care community consists largely of independent practices using at least 20
      different EHR products. This paper discusses the processes undertaken to develop
      a communitywide EHR disease registry in WNY, improvements it engendered, barriers
      overcome, and the lessons learned. METHODS: HEALTHeLINK, under the Office of the
      National Coordinator for Health Information Technology Beacon Community
      Initiative, reached out to 98 primary care practices in the WNY region to
      establish EHR-based diabetes registries. Working with practices, community
      partners, and vendors, registry specifications were created. The registry was
      piloted with practices using one local vendor's EHR product and then rolled out
      to other practices, including five other EHR products. Using identified and de
      identified registry datasets, quality benchmarking within and between practices
      and population health management were undertaken. FINDINGS: From 2011 to 2013,
      the WNY Beacon Community assisted 98 practices (344 providers) serving over
      50,000 adult diabetic patients. A major focus was on EHR registry development
      across diverse systems, and overcoming the challenges this presented. The Beacon
      diabetes registry was implemented at 85 of the 98 targeted practices. Of these
      registries, 65 met the criteria described in a later section for quality
      benchmarking and population health management purposes. Practices received
      quarterly benchmark reports summarizing their performance on key diabetes quality
      metrics and were compared to community practice averages. Practices used their
      registries for population health management by identifying and targeting patients
      in need of follow-up or specific diabetes-related care. DISCUSSION AND
      CONCLUSION: The creation of the registry infrastructure required unified registry
      technical specifications as well as close collaboration between all parties
      involved. The WNY experience showed that a useful disease registry can be
      established in a community largely consisting of numerous disparate primary care
      practices. This laid the groundwork for the future use of EHR data for a variety
      of purposes in the community. The methods used and lessons learned through this
      endeavor may benefit other communities in a similar position, with several
      disconnected EHRs, to establish unified registries.

PMID- 25848618
TI  - Creating a connected community: lessons learned from the Western new york beacon
      community.
AB  - INTRODUCTION: Secure exchange of clinical data among providers has the potential
      to improve quality, safety, efficiency, and reduce duplication. Many communities
      are experiencing challenges in building effective health information exchanges
      (HIEs). Previous studies have focused on financial and technical issues regarding
      HIE development. This paper describes the Western New York (WNY) HIE growth and
      lessons learned about accelerating progress to become a highly connected
      community. METHODS: HEALTHeLINK, with funding from the Office of the National
      Coordinator for Health Information Technology (ONC) under the Beacon Community
      Program, expanded HIE usage in eight counties. The communitywide transformation
      process used three main drivers: (1) a communitywide Electronic Health Record
      (EHR) adoption program; (2) clinical transformation partners; and (3) HIE
      outreach and infrastructure development. RESULTS: ONC Beacon Community funding
      allowed WNY to achieve a new level in the use of interoperable HIE. Electronic
      delivery of results into the EHR expanded from 23 practices in 2010 to 222
      practices in 2013, a tenfold increase. There were more than 12.5 million results
      delivered electronically (HL7 messages) to 222 practices' EHRs via the HIE in
      2013. Use of a secure portal and Virtual Health Record (VHR) to access reports
      (those not delivered directly to the EHR) also increased significantly, from
      13,344 report views in 2010 to over 600,000 in 2013. DISCUSSION AND CONCLUSION:
      The WNY Beacon successfully expanded the sharing of clinical information among
      different sources of data and providers, creating a highly connected community to
      improve the quality and continuity of care. Technical, organizational, and
      community lessons described in this paper should prove beneficial to others as
      they pursue efforts to create connected communities.

PMID- 25848617
TI  - Emphasizing Public Health Within a Health Information Exchange: An Evaluation of
      the District of Columbia's Health Information Exchange Program.
AB  - INTRODUCTION: Clinovations Government Solutions (CGS) was contracted in 2013 to
      conduct a mixed-methods evaluation of the District of Columbia (D.C.) Health
      Information Exchange (HIE) program as part of their Cooperative Agreement Grant
      funded by the Office of the National Coordinator in 2010. The evaluation was to
      focus on the progress of the HIE, how many providers and hospitals were
      participating in the program, and what benefits were being realized through the
      use of the HIE. During the course of the evaluation, the CGS team found that the
      use of the HIE to support public health reporting was one of its core elements.
      BACKGROUND: The D.C. HIE is one of 56 HIE that were funded out of the Cooperative
      Agreement program. The HIE program was managed by the District of Columbia
      Department of Health Care Finance (DHCF), which also manages the District of
      Columbia Medicaid Program. The program was initially designed to accomplish the
      following: developing state-level directories and enabling technical services for
      HIE within and across states; ensuring an effective model for governance and
      accountability; coordinating an integrated approach with Medicaid and public
      health; and developing or updating privacy and security requirements for HIE
      within and across state borders. As the evaluation progressed, the CGS team
      discovered that the relationship between the DHCF and the District of Columbia
      Department of Health (DOH) had become a cornerstone of the D.C. HIE program.
      METHODS: The CGS team used a mixed-methods approach for the evaluation, including
      a review of documents developed by the DHCF in its HIE program, including its
      original application. We also conducted 10 key informant interviews and moderated
      two small-group discussions using a semistructured protocol; and we developed a
      survey that measured the use, satisfaction, and future sustainability of the HIE
      for over 200 providers within the District of Columbia. FINDINGS: While the
      evaluation focused on the D.C. HIE program in its entirety, the results indicated
      the value of utilizing the HIE for public health reporting to enhance the
      surveillance activities of the DOH. Specifically, the DHCF and DOH collaboration
      resulted in using the HIE to electronically capture and report immunization data;
      and in requiring electronic lab reporting and results as part of the Meaningful
      Use Requirement-which can assist in detecting HIV/AIDS and providing better care
      for the district's high population of individuals with HIV/AIDS. Electronic lab
      reporting and electronic prescribing within the HIE can assist the DOH and
      providers in identifying specific diseases, such as tuberculosis and viral
      hepatitis, before they affect a significant part of the population. DISCUSSION:
      Given the severe health disparities in the district, the ability of the D.C. HIE
      program to collect public health information on affected populations will be
      instrumental in better understanding and identifying methods of supporting these
      populations through improved surveillance and identification of the appropriate
      treatments. The D.C. HIE program is uniquely positioned to support these
      populations due to the partnership of DHCF with the D.C. DOH. CONCLUSION AND NEXT
      STEPS: The District of Columbia has made significant strides in expanding its
      public health infrastructure and activities. Three key areas of growth were
      identified that have the potential to transform the District of Columbia's public
      health approach: establishing sufficient feedback loops, collection of
      environmental data, integration, and interoperability.

PMID- 25848619
TI  - Building and strengthening infrastructure for data exchange: lessons from the
      beacon communities.
AB  - INTRODUCTION: The Beacon Community Cooperative Agreement Program supports
      interventions, including care-delivery innovations, provider performance
      measurement and feedback initiatives, and tools for providers and consumers to
      enhance care. Using a learning health system framework, we examine the Beacon
      Communities' processes in building and strengthening health IT (HIT)
      infrastructures, specifically successes and challenges in sharing patient
      information to improve clinical care. BACKGROUND: In 2010, the Office of the
      National Coordinator for Health Information Technology (ONC) launched the three
      year program, which provided $250 million to 17 Beacon Communities to invest in
      HIT and health information exchange (HIE) infrastructure. Beacon Communities used
      this funding to develop and disseminate HIT-enabled quality improvement practices
      found effective in particular community and practice environments. METHODS: NORC
      conducted 7 site visits, November 2012-March 2013, selecting Communities to
      represent diverse program features. From August-October 2013, NORC held
      discussions with the remaining 10 Communities. Following each visit or
      discussion, NORC summarized the information gathered, including transcripts, team
      observations, and other documents the Community provided, to facilitate a within
      Community analysis of context and stakeholders, intervention strategies, enabling
      factors, and challenges. RESULTS: Although each Community designed and
      implemented data-sharing strategies in a unique environment, similar challenges
      and enabling factors emerged across the Beacons. From a learning health system
      perspective, their strategies to build and strengthen data-sharing
      infrastructures address the following crosscutting priorities: promoting
      technical advances and innovations by helping providers adapt EHRs for data
      exchange and performance measurement with customizable IT and offering technical
      support to smaller, independent providers; engaging key stakeholders; and
      fostering transparent governance and stewardship of the infrastructure with
      neutral conveners. CONCLUSION: While all the Communities developed or
      strengthened data-exchange infrastructure, each did this in a unique environment
      of existing health care market and legal factors. The Communities, however,
      encountered similar challenges and enabling factors. Organizations undertaking
      collaborative data sharing, performance measurement and clinical transformation
      can learn from the Beacon Communities' experience.

PMID- 25848620
TI  - Beacon communities' public health initiatives: a case study analysis.
AB  - INTRODUCTION: The Beacon Communities for Public Health (BCPH) project was
      launched in 2011 to gain a better understanding of the range of activities
      currently being conducted in population- and public health by the Beacon
      Communities. The project highlighted the successes and challenges of these
      efforts with the aim of sharing this information broadly among the public health
      community. BACKGROUND: The Beacon Community Program, designed to showcase
      technology-enabled, community-based initiatives to improve outcomes, focused on:
      building and strengthening health information technology (IT) infrastructure and
      exchange capabilities; translating investments in health IT to measureable
      improvements in cost, quality, and population health; and, developing innovative
      approaches to performance measurement, technology, and care delivery. METHODS:
      Four multimethod case studies were conducted based on a modified sociotechnical
      framework to learn more about public health initiative implementation and use in
      the Beacon Communities. Our methodological approach included using document
      review and semistructured key informant interviews. NACCHO Model Practice Program
      criteria were used to select the public health initiatives included in the case
      studies. FINDINGS: Despite differences among the case studies, common barriers
      and facilitators were found to be present in all areas of the sociotechnical
      framework application including structure, people, technology, tasks, overarching
      considerations, and sustainability. Overall, there were many more facilitators
      (range = 7-14) present for each Beacon compared to barriers (range = 4-6).
      DISCUSSION: Four influential promising practices were identified through the
      work: forging strong and sustainable partnerships; ensuring a good task
      technology fit and a flexible and iterative design; fostering technology
      acceptance; and, providing education and demonstrating value. CONCLUSIONS: A
      common weakness was the lack of a framework or model for the Beacon Communities
      evaluation work. Sharing a framework or approach to evaluation at the beginning
      of implementation made the work more effective. Supporting evaluation to inform
      future implementations is important.

PMID- 25848621
TI  - Supporting primary care practices in building capacity to use health information
      data.
AB  - INTRODUCTION: Our objective was to describe essential support resources and
      strategies in order to advance the pace and scope of the use of health
      information technology (HIT) data. BACKGROUND AND CONTEXT: Primary data were
      collected between January 2011 and October 2012. The primary study population
      comprised 51 primary care practices enrolled in the Colorado Beacon Consortium in
      western Colorado. METHODS: We used qualitative methods embedded in a mixed-method
      evaluation: monthly narrative reports from practices; interviews with providers
      and staff; and focused, group discussions with quality improvement (QI) advisors
      and staff from the Health Information Technology Regional Extension Center.
      FINDINGS: Practices valued effective support strategies to assist with using HIT,
      including the following: translating rules and regulations into individual
      practice settings; facilitating peer-to-peer connections; providing processes and
      tools for practice improvement; maintaining accountability and momentum; and
      providing local electronic health record (EHR) technical expertise. Benefits of
      support included improved quality measures, operational improvements, increased
      provider and staff engagement, and deeper understanding of EHR data. DISCUSSION:
      The findings affirm the utility of practice facilitation for HIT-focused aims
      with personalized attention and cross-fertilization among practices for
      improvements. Facilitation to sustain ongoing improvements and prepare for future
      HIT-intensive improvement activities was highly valued. In addition to the
      general practice facilitator, an EHR technical expert was critical to improving
      practice capacity to use electronic clinical data. Collaborative learning expands
      the pool of mentors and teachers, who can further translate their own lessons
      into practical advice for their peers, yielding the emergence of a stronger sense
      of community among the practices. CONCLUSIONS: Using HIT more effectively in
      primary care will require sustained, focused efforts by practices as regulations,
      incentives and HIT evolve. Ongoing support for community-based practice
      facilitators; collaborative learning; and local, personalized EHR advisors will
      help practices care for patients while more effectively deploying HIT to improve
      care.

PMID- 25848622
TI  - Enhancing a geriatric emergency department care coordination intervention using
      automated health information exchange-based clinical event notifications.
AB  - PURPOSE: In a health care system where patients often have numerous providers and
      multiple chronic medical conditions, interoperability of health information
      technology (HIT) is of paramount importance. Regional health information
      organizations (RHIO) often provide a health information exchange (HIE) as a
      solution, which gives stakeholders access to clinical data that they otherwise
      would not otherwise have. A secondary use of preexisting HIE infrastructure is
      clinical event notification (CEN) services, which send automated notifications to
      stakeholders. This paper describes the development and implementation of a CEN
      service enabled by a RHIO in the New York metropolitan area to improve care
      coordination for patients enrolled in a geriatric emergency department care
      coordination program. INNOVATION: This operational CEN system incorporates
      several innovations that to our knowledge have not been implemented previously.
      They include the near real-time notifications and the delivery of notifications
      via multiple pathways: electronic health record (EHR) "in-baskets," email, text
      message to internet protocol-based "zone" phones, and automated encounter entry
      into the EHR. Based on these alerts the geriatric care coordination team contacts
      the facility where the patient is being seen and offers additional information or
      assistance with disposition planning with the goal of decreasing potentially
      avoidable admissions and duplicate testing. FINDINGS: During the nearly one-year
      study period, the CEN program enrolled 5722 patients and sent 497 unique
      notifications regarding 206 patients. Of these notifications, 219 (44%) were for
      emergency department (ED) visits; 121 (55%) of those notifications were received
      during normal business hours when the care coordination team was available to
      contact the ED where the patient was receiving care. Hospital admissions resulted
      from 45% of ED visits 17.8% of these admissions lasted 48 hours or less,
      suggesting some might potentially be avoidable. CONCLUSIONS AND DISCUSSION: This
      study demonstrates the potential of CEN systems to improve care coordination by
      notifying providers of the occurrence of specific events. Although it could not
      directly be demonstrated here, we believe that widespread use of CEN systems have
      potential to reduce potentially avoidable admissions and duplicate testing,
      likely leading to decreased costs.

PMID- 25848623
TI  - The Community Health Applied Research Network (CHARN) Data Warehouse: a Resource
      for Patient-Centered Outcomes Research and Quality Improvement in Underserved,
      Safety Net Populations.
AB  - BACKGROUND: The Community Health Applied Research Network, funded by the Health
      Resources and Services Administration, is a research network comprising 18
      Community Health Centers organized into four Research Nodes (each including an
      academic partner) and a data coordinating center. The network represents more
      than 500,000 diverse safety net patients across 11 states. OBJECTIVE: The primary
      objective of this paper is to describe the development and implementation process
      of the CHARN data warehouse. METHODS: The methods involved regulatory and
      governance development and approval, development of content and structure of the
      warehouse and processes for extracting the data locally, performing validation,
      and finally submitting data to the data coordinating center. PROGRESS TO DATE:
      Version 1 of the warehouse has been developed. Tables have been added, the
      population and the years of electronic health records (EHR) have been expanded
      for Version 2. CONCLUSIONS: It is feasible to create a national, centralized data
      warehouse with multiple Community Health Center partners using different EHR
      systems. It is essential to allow sufficient time: (1) to develop collaborative,
      trusting relationships among new partners with varied technology, backgrounds,
      expertise, and interests; (2) to complete institutional, business, and regulatory
      review processes; (3) to identify and address technical challenges associated
      with diverse data environments, practices, and resources; and (4) to provide
      continuing data quality assessments to ensure data accuracy.

PMID- 25848624
TI  - The utah beacon experience: integrating quality improvement, health information
      technology, and practice facilitation to improve diabetes outcomes in small
      health care facilities.
AB  - PURPOSE: The Utah Improving Care through Connectivity and Collaboration (IC3)
      Beacon community (2010-2013) was spearheaded by HealthInsight, a nonprofit,
      community-based organization. One of the main objectives of IC(3) was to improve
      health care provided to patients with diabetes in three Utah counties,
      collaborating with 21 independent smaller clinics and two large health care
      enterprises. This paper will focus on the use of health information technology
      (HIT) and practice facilitation to develop and implement new care processes to
      improve clinic workflow and ultimately improve patients' diabetes outcomes at 21
      participating smaller, independent clinics. INNOVATION: Early in the project, we
      learned that most of the 21 clinics did not have the resources needed to
      successfully implement quality improvement (QI) initiatives. IC(3) helped clinics
      effectively use data generated from their electronic health records (EHRs) to
      design and implement interventions to improve patients' diabetes outcomes. This
      close coupling of HIT, expert practice facilitation, and Learning Collaboratives
      was found to be especially valuable in clinics with limited resources. FINDINGS:
      Through this process we learned that (1) an extensive readiness assessment
      improved clinic retention, (2) clinic champions were important for a successful
      collaboration, and (3) current EHR systems have limited functionality to assist
      in QI initiatives. In general, smaller, independent clinics lack knowledge and
      experience with QI and have limited HIT experience to improve patient care using
      electronic clinical data. Additionally, future projects like IC(3) Beacon will be
      instrumental in changing clinic culture so that QI is integrated into routine
      workflow. CONCLUSION AND DISCUSSION: Our efforts led to significant changes in
      how practice staff optimized their EHRs to manage and improve diabetes care,
      while establishing the framework for sustainability. Some of the IC(3) Beacon
      practices are currently smoothly transitioning to new models of care such as
      Patient-Centered Medical Homes. Thus, IC(3) Beacon has been instrumental in
      creating a strong community partnership among various organizations to meet the
      shared vision of better health and lower costs, and the experience over the last
      few years has helped the community prepare for the changing health care
      landscape.

PMID- 25848625
TI  - The Southeastern Minnesota Beacon Project for Community-driven Health Information
      Technology: Origins, Achievements, and Legacy.
AB  - INTRODUCTION: The Southeastern (SE) Minnesota Beacon organized all the health
      care providers, county public health organizations, and school districts in the
      deployment and integration of health information exchange (HIE) and targeted
      health communication around childhood asthma and diabetes. The community
      cooperated to establish a clinical data repository for all residents in the 11
      county region. Through this community of practice approach that involved
      traditional and nontraditional providers, the SE Minnesota Beacon was able to
      realize unique applications of this technology. This manuscript overviews the
      associated organization and infrastructure of this community collaboration.
      BACKGROUND: The Office of the National Coordinator for Health Information
      Technology (ONC), as part of the American Recovery and Reinvestment Act of 2009
      (ARRA) stimulus, established 17 projects throughout the United States targeting
      the introduction and meaningful use of health information technology (HIT). These
      17 communities were intended to serve as an example of what could be
      accomplished. The SE Minnesota Beacon is one of these communities. METHODS: The
      community ultimately opted for peer-to-peer HIE, using Nationwide Health
      Information Network (NwHIN) Connect software. The clinical data repository was
      established using the infrastructure developed by the Regenstrief Institute,
      which operated as a trusted third party. As an extension to HIE, the consortium
      of county public health departments created a patient data portal for use by
      school nurses and parents. Childhood asthma was addressed by creating,
      exchanging, and maintaining an "asthma action plan" for each affected child,
      shared throughout the community, including through the patient portal. Diabetes
      management introduced patient treatment decision tools and patient quality of
      life measures, facilitating care. Influenza vaccination was enhanced by large
      scale community reporting in partnership with the state vaccination registry. The
      methodology and principles for arriving at these solutions included community
      engagement, sustainability, scalability, standards, and best practices that fit a
      variety of organizations-from large, robust providers to small organizations.
      FINDINGS: The SE Minnesota Beacon demonstrated that all providers for a
      geographically defined population can cooperate in the development and shared
      governance of a low-cost, sustainable HIE, and the operation of a community
      managed clinical data repository. Furthermore, these infrastructures can be
      leveraged to collaboratively improve the care of patients, as demonstrated for
      childhood asthma and adult diabetes mellitus. CONCLUSION: The shared governance
      of HIT by a community can palpably change the scope and success of collaborations
      targeted to improve patient and community health care.

PMID- 25848626
TI  - Evaluating the Reliability of EHR-Generated Clinical Outcomes Reports: A Case
      Study.
AB  - INTRODUCTION: Quality incentive programs, such as Meaningful Use, operate under
      the assumption that clinical quality measures can be reliably extracted from
      EHRs. Safety Net providers, particularly Federally Qualified Health Centers and
      Look-Alikes, tend to be high adopters of EHRs; however, recent reports have shown
      that only about 9% of FQHCs and Look-Alikes were demonstrating meaningful use as
      of 2013. Our experience working with the Crescent City Beacon Community (CCBC)
      found that many health centers relied on chart audits to report quality measures
      as opposed to electronically generating reports directly from their EHRs due to
      distrust in the data. This paper describes a step-by-step process for improving
      the reliability of data extracted from EHRs to increase reliability of quality
      measure reports, to support quality improvement, and to achieve alignment with
      national clinical quality reporting requirements. BACKGROUND: Lack of
      standardization in data capture and reporting within EHRs drives distrust in EHR
      reported data. Practices or communities attempting to achieve standardization may
      look to CCBC's experience for guidance on where to start and the level of
      resources required in order to execute a data standardization project. During the
      time of this data standardization project, CCBC was launching an HIE. Lack of
      trust in EHR data was a driver for distrust in the HIE data. METHODS: We present
      a case study where a five-step process was used to harmonize measures, reduce
      data errors, and increase trust in EHR clinical outcomes reports among a
      community of Safety Net providers using a common EHR. Primary outcomes were the
      incidence of reporting errors and the potential effect of error types on quality
      measure percentages. The activities and level of resources required to achieve
      these results were also documented by the CCBC program. FINDINGS: Implementation
      of a community-wide data reporting project resulted in measure harmonization,
      reduced reporting burden, and error reduction in EHR-generated clinical outcomes
      reporting across participating clinics over a nine-month period. Increased
      accuracy of clinical outcomes reports provided physicians and clinical care teams
      with better information to guide their decision-making around quality improvement
      planning. DISCUSSION: A number of challenges exist to achieving reliable
      population level quality reporting from EHRs at the practice, vendor, and
      community levels. Our experience demonstrates that quality measure reporting from
      EHRs is not a straightforward process, and it requires time and close
      collaboration between clinics and vendors to improve reliability of reports. Our
      experience found that practices valued the opportunity and step-wise process to
      validate their data locally (out of their EHRs) prior to reporting out of the
      HIE. CONCLUSION AND NEXT STEPS: Communities can achieve higher levels of
      confidence in quality measure reporting at the population level by establishing
      collaborative user groups that work with EHR vendors as partners and use
      technical assistance to build relationships and trust in EHR-generated reports.
      While this paper describes the first phase of our work around improving
      standardization and reliability of EHR reports, vendors should continue to
      explore modifications for improving data capture (at the front-end) via
      standardized data entry templates.

PMID- 25848627
TI  - IT-enabled Community Health Interventions: Challenges, Opportunities, and Future
      Directions.
AB  - Rising health information technology (HIT) adoption and the increasing
      interoperability of health data have propelled the role of IT in community-wide
      health transformations. Disseminating the challenges and opportunities that the
      early adopters of community-wide HIT interventions have experienced is critical
      for empowering the growing demand for community-based health systems. This
      special issue of eGEMs addresses that need. This issue includes a variety of
      community-based HIT projects covering topics such as governance, informatics, and
      learning health systems. These projects represent a diverse set of stakeholders,
      a wide selection of data sources, and multiple information platforms to collate
      or exchange data. We hope that this special issue of eGEMs will be the first of
      several future issues dedicated to community-wide HIT transformations. 

PMID- 25848628
TI  - Defining information needs for public health systems and services research.
AB  - BACKGROUND: People who lead or manage public health agencies have multiple needs
      for information in order to do their jobs effectively. In seeking to investigate
      "what works" in public health practice, investigators in the field of public
      health systems and services research (PHSSR) have largely overlapping information
      needs but often require a greater detail, specificity, or comprehensiveness than
      is routinely available in public health data systems. PHSSR DATA NEEDS MEETING:
      On April 24, 2014, the PHSSR Center of the University of Kentucky and
      AcademyHealth convened a 1-day meeting of public health practitioners and PHSSR
      investigators to identify PHSSR information needs. Meeting participants
      considered data needs for three PHSSR domains: the organization of public health
      agencies and services, the use of rapidly evolving health information
      technologies, and the financing and economic evaluation of public health
      activities. FUTURE DATA NEEDS: Identifying data needs in these and other PHSSR
      domains requires clarification of research questions, consideration of research
      methods, a balance of imagination and practicality, and investments to extend the
      information captured in existing administrative, financial, and population health
      monitoring systems.

PMID- 25848629
TI  - Linking costs to health outcomes for allocating scarce public health resources.
AB  - INTRODUCTION: Resources for public health (PH) are scarce and policymakers face
      tough decisions in determining their funding priorities. The difficulty of making
      these decisions is compounded by current PH accounting systems, which are ill
      equipped to link fiscal resources to PH outcomes. This paper examines the types
      of revenues and expenditures, health services, and health outcomes that are being
      tracked at the local and state PH levels. The authors provide recommendations for
      strengthening the ability of local and state governments to link expenditures to
      PH outcomes, both within and across jurisdictions. FRAMEWORK AND NEXT STEPS: The
      source of revenue data for most local jurisdictions is the accounting systems
      used for the budgeting and auditing of fiscal activities, and these are primarily
      linked to specific PH programs. In contrast, expenditure data are mostly generic
      and typically span multiple PH programs with no link to specific PH activities.
      Many challenges exist to then link PH activities to health outcomes data, which
      are often collected through separate reporting systems at the local, state, and
      national levels. Policy change at the state level and implementation strategies
      that are standardized across local health departments are required to assess the
      costs and health outcomes of PH activities. CONCLUSION: Information linking PH
      expenditures to health outcomes of PH services could greatly inform the decision
      making process. This information will allow investments in PH to be better
      understood and will provide a strong foundation for the PH services and systems
      research community to understand variation and drive improvement. Ultimately,
      these data could be used to improve accountability at the local and state PH
      department levels.

PMID- 25848630
TI  - The future of public health informatics: alternative scenarios and recommended
      strategies.
AB  - BACKGROUND: In October 2013, the Public Health Informatics Institute (PHII) and
      Institute for Alternative Futures (IAF) convened a multidisciplinary group of
      experts to evaluate forces shaping public health informatics (PHI) in the United
      States, with the aim of identifying upcoming challenges and opportunities. The
      PHI workshop was funded by the Robert Wood Johnson Foundation as part of its
      larger strategic planning process for public health and primary care. WORKSHOP
      CONTEXT: During the two-day workshop, nine experts from the public and private
      sectors analyzed and discussed the implications of four scenarios regarding the
      United States economy, health care system, information technology (IT) sector,
      and their potential impacts on public health in the next 10 years, by 2023.
      Workshop participants considered the potential role of the public health sector
      in addressing population health challenges in each scenario, and then identified
      specific informatics goals and strategies needed for the sector to succeed in
      this role. RECOMMENDATIONS AND CONCLUSION: Participants developed recommendations
      for the public health informatics field and for public health overall in the
      coming decade. These included the need to rely more heavily on intersectoral
      collaborations across public and private sectors, to improve data infrastructure
      and workforce capacity at all levels of the public health enterprise, to expand
      the evidence base regarding effectiveness of informatics-based public health
      initiatives, and to communicate strategically with elected officials and other
      key stakeholders regarding the potential for informatics-based solutions to have
      an impact on population health.

PMID- 25848631
TI  - Community health needs assessments: filling data gaps for population health
      research and management.
AB  - INTRODUCTION: Community health needs assessments (CHNA) are completed to meet
      varied regulatory and statutory requirements for local public health departments,
      tax-exempt 501(c)(3) hospitals, and Federally Qualified Health Centers. Although
      compliance is a motivating factor, these entities are committed to understanding
      the communities they serve and to developing strategies to address health needs
      and inequities in health and health care. FILLING DATA GAPS: CHNAs have the
      potential to improve the health of communities and populations by giving crucial
      qualitative and quantitative context to hospital and patient data, thereby
      enhancing opportunities for health services and clinical outcomes researchers.
      Filling in these data gaps can help to improve population health by highlighting
      community-and social determinant-related dynamics relevant to the improved health
      of the community. CHNAS AND EHRS FOR POPULATION HEALTH: Successful models exist
      that that have used CHNAs and the resulting data to improve population health
      management and reduce inequities, as do health systems that have used the EHR and
      community-based performance measurement data to achieve population health goals.

PMID- 25848632
TI  - Development and Implementation of ExPLORE Clinical Practice, a Web-accessible
      Comparative Outcomes Tool for California Hospitals and Physicians.
AB  - BACKGROUND: Hospital-based clinicians have little information about the outcomes
      of their care, much less how those outcomes compare with those of their peers. A
      variety of care quality indicators have been developed, but comparisons tend to
      be hospitalwide, and often irrelevant to the practice and patient group of many
      hospital clinicians. Moreover, information is not enough to transform clinical
      practice, as the human response to such comparisons is, "I'm doing the best I
      know how." What is needed is granular, clinically specific feedback with peer
      mediated advice about how "positive deviants" achieve better results. OBJECTIVE:
      This case study reports on the development and implementation of a web-accessible
      comparative outcomes tool, ExPLORE Clinical Practice, for hospitals and
      clinicians in California. METHODS: We use iterative development and refinement of
      web tools to report comparative outcomes; incremental development of suites of
      procedure-patient outcome pairs specific to particular medical specialty groups;
      testing and refinement of response time metrics to reduce delays in report
      generation; and introduction of a comments section for each measure that assists
      with interpretation and ties results to strategies found to lead to better
      clinical outcomes. RESULTS: To date, 76 reports, each with 115 to 251
      statistically evaluated outcomes, are available electronically to compare
      individual hospitals in California to statewide outcomes. DISCUSSION AND
      CONCLUSIONS: ExPLORE Clinical Practice is one of a number of emerging systems
      that attempt to lever available data to improve patient outcomes. The ExPLORE
      Clinical Practice system combines a clinical focus on highly specific outcome
      measures with attention to technical issues such as crafting an intuitive user
      interface and graphic presentation. This case study illustrates the important
      advances made in using data to support clinicians to improve care for patients.
      We see this information as a way to start local conversations about quality
      improvement, and as a means of generating peer advice for improving patient
      outcomes.

PMID- 25848633
TI  - Adapting practice-based intervention research to electronic environments:
      opportunities and complexities at two institutions.
AB  - BACKGROUND AND PURPOSE: Primary care practice-based research has become more
      complex with increased use of electronic health records (EHRs). Little has been
      reported about changes in study planning and execution that are required as
      practices change from paper-based to electronic-based environments. We describe
      the evolution of a pediatric practice-based intervention study as it was adapted
      for use in the electronic environment, to enable other practice-based researchers
      to plan efficient, effective studies. METHODS: We adapted a paper-based pediatric
      office-level intervention to enhance parent-provider communication about
      subspecialty referrals for use in two practice-based research networks (PBRNs)
      with partially and fully electronic environments. We documented the process of
      adaptation and its effect on study feasibility and efficiency, resource use, and
      administrative and regulatory complexities, as the study was implemented in the
      two networks. RESULTS: Considerable time and money was required to adapt the
      paper-based study to the electronic environment, requiring extra meetings with
      institutional EHR-, regulatory-, and administrative teams, and increased practice
      training. Institutional unfamiliarity with using EHRs in practice-based research,
      and the consequent need to develop new policies, were major contributors to
      delays. Adapting intervention tools to the EHR and minimizing practice
      disruptions was challenging, but resulted in several efficiencies as compared
      with a paper-based project. In particular, recruitment and tracking of subjects
      and data collection were easier and more efficient. CONCLUSIONS: Practice-based
      intervention research in an electronic environment adds considerable cost and
      time at the outset of a study, especially for centers unfamiliar with such
      research. Efficiencies generated have the potential of easing the work of study
      enrollment, subject tracking, and data collection.

PMID- 25848634
TI  - Style Guide: An Interdisciplinary Communication Tool to Support the Process of
      Generating Tailored Infographics From Electronic Health Data Using EnTICE3.
AB  - PURPOSE: In this case study we describe key features of the structured
      communication tool-a style guide-used to support interdisciplinary collaboration,
      and we propose the use of such a tool for research teams engaged in similar
      projects. We employ tailored infographics to present patient reported outcome
      data from a community health survey back, in a comprehensible and actionable
      manner, to the individuals who provided it. The style guide was developed to
      bridge the semantic gap between the domain and programming experts engaged in
      this effort. INNOVATION: The style guide supports the communication of complex
      design specifications in a highly structured format that is nevertheless flexible
      enough to accommodate project growth. Unlike the typical corporate style guide
      that has a more narrative format, our style guide is innovative in its use of
      consistent fields across multiple, standalone entries. CREDIBILITY: The process
      of populating the style guide prompted the designer toward greater design
      efficiency and led to consistent and specific instructions that met the framework
      architect's stated information needs. DISCUSSION AND CONCLUSION: The guiding
      values in the creation of the style guide were consistency, clarity, and
      flexibility. It serves as a durable reference to the desired look and
      functionality of the final infographic product without dictating an
      implementation strategy. The style guide format can be adapted to meet the
      communication needs of other interdisciplinary teams facing a semantic gap.

PMID- 25848635
TI  - Quality measure performance in small practices before and after electronic health
      record adoption.
AB  - INTRODUCTION: To date, little research has been published on the impact that the
      transition from paper-based record keeping to the use of electronic health
      records (EHR) has on performance on clinical quality measures. This study
      examines whether small, independent medical practices improved in their
      performance on nine clinical quality measures soon after adopting EHRs. METHODS:
      Data abstracted by manual review of paper and electronic charts for 6,007
      patients across 35 small, primary care practices were used to calculate rates of
      nine clinical quality measures two years before and up to two years after EHR
      adoption. RESULTS: For seven measures, population-level performance rates did not
      change before EHR adoption. Rates of antithrombotic therapy and smoking status
      recorded increased soon after EHR adoption; increases in blood pressure control
      occurred later. Rates of hemoglobin A1c testing, BMI recorded, and cholesterol
      testing decreased before rebounding; smoking cessation intervention, hemoglobin
      A1c control and cholesterol control did not significantly change. DISCUSSION: The
      effect of EHR adoption on performance on clinical quality measures is mixed. To
      improve performance, practices may need to develop new workflows and adapt to
      different documentation methods after EHR adoption. CONCLUSIONS: In the short
      term, EHRs may facilitate documentation of information needed for improving the
      delivery of clinical preventive services. Policies and incentive programs
      intended to drive improvement should include in their timelines consideration of
      the complexity of clinical tasks and documentation needed to capture performance
      on measures when developing timelines, and should also include assistance with
      workflow redesign to fully integrate EHRs into medical practice.

PMID- 25848636
TI  - Recruiting for Acute Myocardial Infarction Cell Therapy Trials: Challenges and
      Best Practices for the CCTRN.

PMID- 25848637
TI  - Morphological methods to evaluate protective agents against aminoglycoside
      induced nephrotoxicity.

PMID- 25848638
TI  - Important statistical points to improve and promote the methodology of the
      articles on medical sciences, particularly nephrology and kidney; a review
      article.
AB  - BACKGROUND: Quality of articles' methodology is one of the important factors
      which is considered by researchers. OBJECTIVES: This study was conducted to
      determine statistical guidelines on promotion of methodology's quality in the
      articles concerning medical sciences, particularly nephrology, to assist authors
      and reviewers. MATERIALS AND METHODS: This study is a systematic review.
      Initially, the keywords "Epidemiologic Methods/analysis" [Mesh] OR "Epidemiologic
      Methods/epidemiology" and "reporting" were selected in Medline database. Then,
      reliable databases were searched for relevant publications. Being relevant,
      containing viewpoints, and recommending statistical guidelines as well as
      approval of at least two of the three examiners of articles were determined as
      the inclusion criteria into the study. RESULTS: Two hundred relevant articles
      were retrieved. Thirty-two articles met the inclusion criteria. By the examined
      articles, 30 applied points have determinative role for improving and promoting
      quality of articles methodology. Of the important points, introducing and
      describing target community and statistical population, mentioning article title,
      introducing independent and dependent variables as well as confounders, reporting
      sample size for subgroups and the whole study, summarizing the data according to
      their statistical distribution (reporting mean and standard deviation for data
      with normal distribution), reporting the type of rate (incidence, survival),
      ratio (odds, hazard) or risk (absolute, relative, difference) with 95% CI and the
      used software could be mentioned. CONCLUSION: The most important factors
      contributing greatly to the quality of articles' methodology on nephrology were
      reported in the present study. Applying these factors by articles authors and
      reviewers could lead to improve articles' and journals' quality. In addition, use
      of the findings of the present study in articles' materials and methods could
      avoid research errors.

PMID- 25848639
TI  - Perieccrine and pericapillary calcification in calciphylaxis.

PMID- 25848640
TI  - Assessing of the relationship between renal function tests and retinopathy stage
      in patients with type II diabetes.
AB  - INTRODUCTION: Retinopathy and nephropathy are long-term diabetes complications
      which are associated together. Renal dysfunction is a risk factor for progression
      and deterioration of diabetic retinopathy. Diabetes causes damage to the small
      blood vessels in the retina and kidney which eventually resulted in diabetic
      nephropathy, renal failure and blindness. Due to the high cost for treating of
      these complications it is better to prevent them. OBJECTIVES: We aimed to assess
      the patients' kidney function and retinal status in a group of diabetic patients
      to find probable association between nephropathy and retinopathy hence can
      prevent from serious renal complications. PATIENTS AND METHODS: In this cross
      sectional study 253 patients with type 2 diabetes referring to ophthalmology
      clinics were evaluated. Eye examination was conducted by an ophthalmologist
      (vitreoretinal subspecialist) and disease stage was determined, then serum blood
      urea nitrogen (BUN) and creatinine tests and 24-hour urine collection for
      microalbuminuria were measured. RESULTS: Mean of BUN and microalbuminuria had
      significant difference in three groups including proliferative retinopathy, non
      proliferative retinopathy and patients without retinopathy. The mean (+/- SD) of
      serum creatinine in patients with proliferative retinopathy, non-proliferative
      retinopathy and patients without retinopathy had no significant difference.
      CONCLUSION: The presence or absence of retinopathy in the early stages of
      diabetic kidney disease has not related to renal involvement, in fact, patients
      without retinopathy may have renal involvement. In periodic examination, diabetic
      patients should be evaluated for microalbuminuria in addition to renal function
      test examination.

PMID- 25848641
TI  - Effect of metabolic syndrome and its components on survival in colorectal cancer:
      a prospective study.
AB  - INTRODUCTION: Metabolic syndrome (MetS) may affect prognosis of the patients
      diagnosed with colorectal cancer (CRC). OBJECTIVES: This study was aimed to
      design a model and to examine the prognostic effect of MetS on survival time in
      the patients with CRC. PATIENTS AND METHODS: Data were collected from 1127 cases
      of CRC from Cancer Registry Center of the Research Institute of Gastroenterology
      and Liver Disease, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
      In this cohort study, patients were divided into two groups based on the presence
      of MetS. We tested the prognostic value of MetS in the patients by Cox
      proportional hazard modeling. RESULTS: Mean +/- standard deviation of the
      patients' age at diagnosis in MetS group and non-MetS group was 56 +/- 13 years
      old and 53 +/- 15 years old respectively. Tumor stage as an independent variable
      affected CRC survival. The mean survival time of the MetS and non-MetS groups was
      23 and 27 months respectively. Independent variables like tumor stage (hazard
      ratio [HR], 1.76; 95% CI, 0.29-0.90) and educational level (HR, 0.50; 95% CI,
      0.23-0.97) had significant effect on CRC survival and MetS (HR, 0.95; 95% CI,
      0.52-1.5), tumor size (HR, 1.390; 95% CI, 1.237-1.560), family history, age,
      gender, and smoking had non-significant effect on CRC survival. CONCLUSION: MetS
      could be a prognostic factor for survival in the patients with CRC. The results
      suggested that effect of MetS was not significant.

PMID- 25848642
TI  - A facile synthesis of fluorescent silver nanoclusters with human ferritin as a
      synthetic and interfacing ligand.
AB  - Water-soluble fluorescent silver nanoclusters (NCs) formed on biomolecule ligands
      have been extensively studied due to their great potential as new biocompatible
      fluorescent materials for biosensors. As synthetic ligands, proteins in
      particular can provide unique structures and functions to the assembled
      fluorescent silver clusters. A key challenge, however, is to develop appropriate
      protein ligands and synthetic approaches for cluster formation, especially using
      native aqueous solutions, to fully preserve the valuable properties of the
      protein templates. Here we report a human ferritin-templated synthesis of
      fluorescent silver NCs under neutral aqueous buffer conditions. The unique metal
      binding property of ferritin and an optimized silver ion reduction allowed us to
      produce highly stable fluorescent silver NCs that are steadily assembled in the
      cage-like ferritin proteins. The fluorescent clusters were also successfully
      assembled on genetically engineered ferritin with antibody-binding protein G. The
      resulting protein G-ferritin-silver NC complex fully retained the ferritin
      structure as well as the antibody binding ability. The present silver
      nanoclusters on ferritin (Ft-Ag NCs) also showed highly specific Cu(2+)-induced
      fluorescence quenching. By exploiting the large but stable nature of ferritin, we
      fabricated a highly robust and porous hydrogel sensor system for rapid Cu(2+)
      detection, where the Ft-Ag NCs were stably encapsulated in surface-bound
      hydrogels with large pore sizes. Our Ft-Ag NCs that are formed under native
      aqueous conditions will have great potential as a new fluorescent material with
      the high structural and functional diversities of ferritin. 

PMID- 25848643
TI  - An artificial receptor synthesized by surface-confined imprinting for the
      recognition of acetylation on histone H4 K16.
AB  - A novel artificial receptor has been synthesized using surface-confined
      imprinting for the recognition of lysine acetylation in histone H4. The material
      has high recognition fidelity and epitope affinity. It was demonstrated that
      acetylated Lys plays a role in binding site creation and peptide imprinting can
      be performed in phosphate buffer. 

PMID- 25848644
TI  - Fingerprints of short-range and long-range structure in BaZr(1-x)HfxO3 solid
      solutions: an experimental and theoretical study.
AB  - A microwave-assisted hydrothermal method was applied to synthesize BaZr1-xHfxO3,
      (BZHO) solid solutions at a low temperature, 140  degrees C, and relatively short
      times, 160 min. The detailed features of the crystal structure, at both short and
      long ranges, as well as the crystal chemistry doping process, are extensively
      analysed. X-ray diffraction measurements and Raman spectroscopy have been used to
      confirm that pure and Hf-doped BZO materials present a cubic structure. Extended
      X-ray absorption fine structure (EXAFS) spectra indicate that Hf(4+) ions have
      replaced the Zr(4+) ions on the 6-fold coordination and a subsequent change on
      the Ba(2+) 12-fold coordination can be sensed. X-ray absorption near-edge
      structure (XANES) spectroscopy measurements reveal a local symmetry breaking
      process, associated to overlap of the 4d-2p and 5d-2p orbitals of Zr-O and Hf-O
      bonds, respectively. Field emission scanning electron microscopy (FE-SEM) and
      high resolution transmission electron microscopy (HRTEM) show the mesocrystalline
      nature of self-assembled BZHO nanoparticles under a dodecahedron shape. In
      addition first principle calculations were performed to complement the
      experimental data. The analysis of the band structures and density of states of
      the undoped BZO and doped BZHO host lattice allow deep insight into the main
      electronic features. The theoretical results help us to find a correlation
      between simulated and experimental Raman modes and allow a more substantial
      interpretation of crystal structure. 

PMID- 25848645
TI  - Modulation of band gap by an applied electric field in silicene-based hetero
      bilayers.
AB  - Electronic properties of the hetero-structures consisting of silicene, graphene
      and BN monolayers under the influence of an electric field were investigated
      using density functional theory. With no electric field, both silicene/graphene
      and silicene/BN were shown to have a finite gap of about ~50 meV, though silicene
      is a zero-gap two-dimensional material. Application of the field perpendicular to
      the bilayer system was found to facilitate modulation of the band gap, exhibiting
      an approximately linear relationship with the gap energy, in contrast to what was
      seen for the constituent monolayers. Also, the degree of the modulation was
      mainly determined by the Si-pz electronic states at the interface of the
      silicene/graphene and silicene/BN bilayers. 

PMID- 25848646
TI  - Poly(3-hydroxybutyrate-co-4-hydroxybutyrate) based nanocomposites: influence of
      the microstructure on the barrier properties.
AB  - Poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P3HB-co-4HB) films containing
      various contents of organo-modified montmorillonite C30B nanoclays were prepared
      by melt intercalation. Wide angle X-ray diffraction measurements and transmission
      electron microscopy observations evidenced aggregated and intercalated structures
      with individual nanoclay platelets in the nanocomposites and an orientation of
      nanoclays. Differential scanning calorimetry measurements showed that the
      nanoclay did not influence the crystalline structure of the matrix because it is
      mainly located in the polymer amorphous phase. The influence of the filler on the
      barrier properties of the film was evaluated by water diffusion, gas permeation
      (CO2, N2, O2) and liquid water sorption measurements. A decrease of the N2
      permeability was measured due to the tortuosity effect of the filler associated
      with a decrease of the solubility within the matrix. The influence of the filler
      was more marked for O2 due to the larger decrease of O2 solubility. In contrast,
      the CO2 permeability increased whatever the filler content because of a
      facilitated transport mechanism due induced by the presence of quaternary
      ammonium cations on the C30B surface. The decrease of the water permeability with
      the filler was explained by a competition between the kinetic (diffusivity) and
      thermodynamic (solubility) contributions defining the permeability process. 

PMID- 25848647
TI  - Phase control of a perovskite transition-metal oxide through oxygen displacement
      at the heterointerface.
AB  - Controlling structural distortions that are closely related to functional
      properties in transition-metal oxides is a key not only to exploring novel
      phenomena but also to developing novel oxide-based electronic devices. In this
      review article, we overview investigations revealing that oxygen displacement at
      the heterointerface is a key parameter characterizing structure-property
      relationships of heterostructures. We further demonstrate that the interface
      engineering of the oxygen displacement is useful to control structural and
      electronic properties of strained oxides. 

PMID- 25848648
TI  - Synthesis and characterization of three amino-functionalized metal-organic
      frameworks based on the 2-aminoterephthalic ligand.
AB  - The incorporation of Lewis base sites and open metal cation sites into metal
      organic frameworks (MOFs) is a potential route to improve selective CO2
      adsorption from gas mixtures. In this study, three novel amino-functionalized
      metal-organic frameworks (MOFs): Mg-ABDC [Mg3(ABDC)3(DMF)4], Co-ABDC
      [Co3(ABDC)3(DMF)4] and Sr-ABDC [Sr(ABDC)(DMF)] (ABDC = 2-aminoterephthalate) were
      synthesized by solvothermal reactions of 2-aminoterephthalic acid (H2ABDC) with
      magnesium, cobalt and strontium metal centers, respectively. Single-crystal
      structure analysis showed that Mg-ABDC and Co-ABDC were isostructural compounds
      comprising two-dimensional layered structures. The Sr-ABDC contained a three
      dimensional motif isostructural to its known Ca analogue. The amino
      functionalized MOFs were characterized by powder X-ray diffraction, thermal
      gravimetric analysis and N2 sorption. The CO2 and N2 equilibrium adsorption
      capacities were measured at different temperatures (0 and 25  degrees C). The
      CO2/N2 selectivities of the MOFs were 396 on Mg-ABDC, 326 on Co-ABDC and 18 on Sr
      ABDC. Both Mg-ABDC and Co-ABDC exhibit high heat of CO2 adsorption (>30 kJ mol(
      1)). The Sr-ABDC displays good thermal stability but had a low adsorption
      capacity resulting from narrow pore apertures. 

PMID- 25848649
TI  - Effects of dry heating on the progression of in vitro digestion of egg white
      proteins: contribution of multifactorial data analysis.
AB  - The impact of dry heating on the progression of in vitro digestion of egg white
      proteins was investigated through application of multiple factor analysis (MFA)
      to electrophoresis data. Dry heating (from 1 to 10 days between 60 and 90 
      degrees C) enhanced protein unfolding and aggregation, thus generating different
      SDS-PAGE patterns for each sample before digestion. The progression of in vitro
      digestion was then modified according to the degree of protein unfolding and/or
      aggregation. In vitro digestion tended to decrease the heterogeneity of sample
      electrophoretic patterns overall but it occurred either at the very beginning of
      the gastric stage or throughout the gastric stage or again during the duodenal
      stage, depending on the heat treatment to which the sample had been subjected. At
      the end of digestion, three groups of samples were obtained: all samples dry
      heated at 60  degrees C and one sample dry heated for 1 day at 70  degrees C that
      were more hydrolysed than the control, samples dry heated for more than 2 days at
      80  degrees C or 90  degrees C that were less hydrolysed than the control, and
      samples dry heated for more than 2 days at 70  degrees C or 1 day at 80 or 90 
      degrees C that were as hydrolysed as the control. 

PMID- 25848651
TI  - Fast identification and quantification of BTEX coupling by Raman spectrometry and
      chemometrics.
AB  - Monoaromatic hydrocarbons (MAHs) monitoring is of environmental interest since
      these chemical pollutants are omnipresent. While waiting for robust sensors able
      to detect hydrocarbons at very low levels, the present study shows how each
      compound from pure BTEX mixtures can be identified fast and quantified thanks to
      Raman spectrometry and data processing based on the SIMPLISMA algorithm. A
      preprocessing module has been created to remove background contributions and a
      postprocessing program has been added to achieve matching and calibration. A wide
      range of BTEX concentrations and relative proportions has been investigated in
      order to determine the limitations of the processing. Output results achieved an
      accuracy of up to 95%. This method could be extended to other important
      pollutants such as polyaromatic hydrocarbons (PAHs) and chlorinated hydrocarbon
      derivatives. 

PMID- 25848652
TI  - Direct arsenic(III) sensing by a renewable gold plated Ir-based microelectrode.
AB  - We aim to determine arsenic(III) in natural aquatic systems in the nanomolar
      range and at natural pH. In view of a future application of a gel integrated
      electrochemical detection approach to reduce fouling and to control mass
      transport, we introduce here a microelectrode capable of quantifying As(III) that
      consists of a gold plated Ir-based microelectrode (Au-IrM). The key advantage of
      this approach is the ability to renew the Au layer by electrochemical control for
      better robustness in the field. The microsensor was electrochemically
      characterized by Square Wave Anodic Stripping Voltammetry. The obtained results
      demonstrate that the stripping peaks exhibit reproducible linear calibration
      curves at pH 8 for As(III) concentrations from 10 to 50 nM and from 1 to 10 nM,
      using 3 and 36 min preconcentration times, respectively. The interference by
      copper and chloride is negligible for an As : Cu concentration ratio of 1 : 20
      and a chloride concentration of 0.6 M typically found in seawater. The gold layer
      exhibits a lifetime of 7 days. The measurements are reproducible over time for a
      given gold layer (RSD < 9%) and between renewed layers (RSD <= 12.5%). While this
      work forms the basis for further progress on gel coated microelectrode arrays,
      As(III) detection in freshwater samples was successfully demonstrated here.

PMID- 25848650
TI  - Modeling and analysis of innate immune responses induced by the host cells
      against hepatitis C virus infection.
AB  - An in-depth understanding of complex systems such as hepatitis C virus (HCV)
      infection and host immunomodulatory response is an open challenge for biologists.
      In order to understand the mechanisms involved in immune evasion by HCV, we
      present a simplified formalization of the highly dynamic system consisting of
      HCV, its replication cycle and host immune responses at the cellular level using
      hybrid Petri net (HPN). The approach followed in this study comprises of step
      wise simulation, model validation and analysis of host immune response. This
      study was performed with an objective of making correlations among viral RNA
      levels, interferon (IFN) production and interferon stimulated genes (ISGs)
      induction. The results correlate with the biological data verifying that the
      model is very useful in predicting the dynamic behavior of the signaling proteins
      in response to a stimulus. This study implicates that HCV infection is dependent
      upon several key factors of the host immune response. The effect of host proteins
      on limiting viral infection is effectively overruled by the viral pathogen. This
      study also analyzes activity levels of RNase L, miR-122, IFN, ISGs and PKR
      induction and inhibition of TLR3/RIG1 mediated pathways in response to targeted
      manipulation in the presence of HCV. The results are in complete agreement at the
      time of writing with the published expression studies and western blot
      experiments. Our model also provides some biological insights regarding the role
      of PKR in the acute infection of HCV. It might help to explain why many patients
      fail to clear acute HCV infection while others, with low ISG basal levels, clear
      HCV spontaneously. The described methodology can easily be reproduced, which
      suitably supports the study of other viral infections in a formal, automated and
      expressive manner. The Petri net-based modeling approach applied here may provide
      valuable insights for study design and analyses to evaluate other disease
      associated integrated pathways in biological systems.

PMID- 25848653
TI  - Polymeric catenanes synthesized via "click" chemistry and atom transfer radical
      coupling.
AB  - A novel route for the synthesis of polymeric catenanes was demonstrated by
      grafting an alkyne functionalized polymer onto a supramolecularly templated azide
      terminated ligand followed by ring closure via atom transfer radical coupling
      (ATRC). The polymeric catenane was characterized via GPC and AFM imaging. 

PMID- 25848654
TI  - Growth rates and water stability of 2D boronate ester covalent organic
      frameworks.
AB  - We examine the growth rates, activation energies, and hydrolytic stability of
      multiple 2D boronate ester covalent organic frameworks by turbidity measurements,
      observing a 200-fold range in stability. The rate-determining step in boronate
      ester 2D COF growth is not in-solution condensation, but rather interlayer
      polymer stacking through a nucleation-elongation process. 

PMID- 25848655
TI  - Spontaneous assembly of silylethane-thiol derivatives on Au(111): a chemically
      robust thiol protecting group as the precursor for the direct formation of
      aromatic gold thiolate monolayers.
AB  - Self-assembled monolayers (SAMs) on gold were obtained by the direct absorption
      of a fully conjugated phenylenethienylene derivative () presenting robust
      silylethane-thiol protecting groups as anchoring agents. The thiol deprotection
      and SAM formation have been evidenced by quartz crystal microbalance (QCM)
      measurements and X-ray photoelectron spectroscopy (XPS), and have been compared
      to the SAM obtained from its thioacetate analog (5). The chemically robust
      silylethane-thiol protecting group appeared as a surprisingly effective anchoring
      agent for the preparation of aromatic SAMs on Au(111), suitable for subsequent
      post-functionalization. 

PMID- 25848656
TI  - Statistical carbazole-fluorene-TTBTBTT terpolymers as promising electron donor
      materials for organic solar cells.
AB  - We report the application of a statistical Suzuki-Miyaura polycondensation
      reaction for synthesis of a family of carbazole-fluorene-TTBTBTT terpolymers with
      tailored physical and optoelectronic properties. Organic bulk heterojunction
      solar cells based on the designed materials with optimal fluorene to carbazole
      ratios yielded reproducible power conversion efficiencies of 6.5-6.7%. 

PMID- 25848657
TI  - 3,4,9,10-Perylenetetracarboxylic acid/o-phenylenediamine nanomaterials as novel
      redox probes for electrochemical aptasensor systems based on an Fe3O4 magnetic
      bead as a nonenzymatic catalyst.
AB  - A novel redox probe 3,4,9,10-perylenetetracarboxylic acid/o-phenylenediamine
      (PTCA/OPD) with well-defined redox peaks caused by the synergistic action between
      them was demonstrated via theoretical and practical research, and applied in an
      electrochemical aptasensor to detect thrombin (TB) based on an Fe3O4 magnetic
      bead (MB) as a nonenzymatic catalyst. 

PMID- 25848658
TI  - Carbon cladded TiO2 nanotubes: fabrication and use in 3D-RuO2 based
      supercapacitors.
AB  - In this work we introduce a facile procedure that allows a highly conformal
      coating of self-organized TiO2 nanotubes (NTs) with a graphite-like thin carbon
      layer. This provides a platform to enhance the functionality of TiO2 nanotubes
      for a wide range of applications. Here we show that such modified nanotubes can
      serve as a 3D scaffold for an ideal decoration with RuO2 nanoparticles. Used as
      3D pseudocapacitor electrode, capacitance values of up to 80 times higher than
      plain TiO2 NTs, and a very high yield of utilization of RuO2 (872 F g(-1)) and
      excellent long-term cycling stability can be reached. 

PMID- 25848659
TI  - Investigating dendrites and side reactions in sodium-oxygen batteries for
      improved cycle lives.
AB  - The development of sodium-oxygen batteries with high round-trip efficiencies is
      hindered by the short cycle lives. Sodium dendrite formation and oxygen crossover
      are identified as two major issues. By employing an ion selective membrane, the
      cycle life of sodium-oxygen batteries has been greatly improved. 

PMID- 25848660
TI  - The pWW0 plasmid imposes a stochastic expression regime to  the chromosomal ortho
      pathway for benzoate metabolism in  Pseudomonas putida.
AB  - Environmental plasmids often expand the metabolic repertoire of bacteria that
      carry them, but they also interfere with the biochemical and genetic network of
      the host. The pWW0 plasmid born by Pseudomonas putida mt-2 encodes the TOL
      pathway for degradation of toluene/m-xylene through production of intermediate
      compounds benzoate/3-methylbenzoate. These can be also recognized as substrates
      by the chromosomally encoded ben and cat gene products, thereby creating a
      manifest regulatory and biochemical conflict. In this context, we have
      investigated how the introduction of the pWW0 plasmid into P. putida affects
      behaviour of the promoter of the ben pathway (Pb) in single cells. Using a series
      of standardized transcriptional fusions to green fluorescent protein, we found
      that acquisition of the TOL pathway switches the activation course of the Pb
      promoter from unimodal/graded to bimodal/stochastic when cells were exposed to
      benzoate. This behaviour was propagated downstream into the Pc promoter of the
      cat gene cluster, which responds to the benzoate-degradation intermediate cis,cis
      muconate. The TOL plasmid thus imposes expression of the chromosomal Pb with a
      stochastic behaviour likely to result in biochemical heterogeneity of the
      otherwise genetically clonal population when exposed to benzoate as a growth
      substrate.

PMID- 25848661
TI  - Preface. Rhodopsin.

PMID- 25848662
TI  - Preface. PCR primer design.

PMID- 25848663
TI  - Reply: To PMID 23940103.

PMID- 25848664
TI  - Reply: To PMID 24401738.

PMID- 25848665
TI  - Allison Doupe: in memoriam.

PMID- 25848666
TI  - Kidney transplantation - the journey  continues.

PMID- 25848667
TI  - Hypersexuality after self-inflicted nail gun penetrating traumatic brain injury
      and neurosurgery: case analysis with literature review.

PMID- 25848668
TI  - [Discovering innovations].

PMID- 25848669
TI  - Decisions about knowledge in medical practice: the effect of temporal features of
      a task.
AB  - A classic question of social science is how knowledge informs practice. Research
      on physicians' decisions about medical knowledge has focused on doctors' personal
      capabilities and features of the knowledge corpus, producing divergent findings.
      This study asks, instead, How is decision making about the use of knowledge
      influenced by features of work? From observations of one team's decisions in
      multiple clinical and administrative contexts, the author argues that making
      decisions is contingent upon temporal features of physicians' tasks. Physicians
      receive feedback at different speeds, and they must account for these speeds when
      judging what they can prioritize. This finding explains doctors' perceived
      uncertainty in other studies as a product of the long feedback loop in tasks, and
      their certainty or pragmatism as a product of shorter feedback loops. In these
      latter scenario's, physicians consider and deploy scientific knowledge after--and
      not before, as is usually assumed--determining a fruitful plan of action.

PMID- 25848670
TI  - Racially and ethnically diverse schools and adolescent romantic relationships.
AB  - Focusing on romantic relationships, which are often seen as a barometer of social
      distance, this analysis investigates how adolescents from different racial-ethnic
      and gender groups respond when they attend diverse schools with many
      opportunities for inter-racial-ethnic dating. Which groups respond by forming
      inter-racial-ethnic relationships, and which groups appear to "work around"
      opportunities for inter-racial-ethnic dating by forming more same-race-ethnicity
      relationships outside of school boundaries? Most prior studies have analyzed only
      relationships within schools and, therefore, cannot capture a potentially
      important way that adolescents express preferences for same-race-ethnicity
      relationships or work around constraints from other groups' preferences. Using
      the National Longitudinal Study of Adolescent Health, I find that, when
      adolescents are in schools with many opportunities for inter-racial-ethnic
      dating, black females and white males are most likely to form same-race-ethnicity
      relationships outside of the school; whereas Hispanic males and females are most
      likely to date across racial-ethnic boundaries within the school.

PMID- 25848671
TI  - Who is black, white, or mixed race? How skin color, status, and nation shape
      racial classification in Latin America.
AB  - Comparative research on racial classification has often turned to Latin America,
      where race is thought to be particularly fluid. Using nationally representative
      data from the 2010 and 2012 America's Barometer survey, the authors examine
      patterns of self-identification in four countries. National differences in the
      relation between skin color, socioeconomic status, and race were found. Skin
      color predicts race closely in Panama but loosely in the Dominican Republic.
      Moreover, despite the dominant belief that money whitens, the authors discover
      that status polarizes (Brazil), mestizoizes (Colombia), darkens (Dominican
      Republic), or has no effect (Panama). The results show that race is both physical
      and cultural, with country variations in racial schema that reflect specific
      historical and political trajectories.

PMID- 25848672
TI  - Sources of sibling (dis)similarity: total family impact on status variation in
      The Netherlands in the nineteenth century.
AB  - The authors describe and explain variation in the occupational status resemblance
      of brothers in The Netherlands during modernization. They test opposing
      hypotheses about how modernization processes influenced fraternal resemblance
      through the value and inequality of family resources based on a job competition
      model in combination with modernization theory, status maintenance theory, and
      dualism theory. The authors use the high-quality, large-scale database GENLIAS,
      yielding digitized information for approximately 450,000 linked Dutch marriage
      certificates from 250,000 families, complemented with historical indicators of
      six modernization processes for over 2,500 communities. Using multilevel meta
      regression models, they find that brother correlations in status decreased slowly
      from about 1860 onward. Although this exactly parallels the period of
      modernization, the authors find that modernization processes were not responsible
      (except possibly urbanization and mass transportation). In fact, in line with
      dualism theory, fraternal resemblance increased with most processes (i.e.,
      industrialization, educational expansion, in-migration, and mass communication)
      because they amplified in-equality.

PMID- 25848675
TI  - Effect of acceptor strength on optical and electronic properties in conjugated
      polymers for solar applications.
AB  - Four new low-bandgap electron-accepting polymers-poly(4,10-bis(2-butyloctyl)-2-(2
      (2-ethylhexyl)-1,1-dioxido-3-oxo-2,3-dihydrothieno[3,4-d]isothiazol-4
      yl)thieno[2',3':5,6]pyrido[3,4-g]thieno[3,2-c]isoquinoline-5,11(4H,10H-dione)
      (PNSW); poly(4,10-bis(2-butyloctyl)-2-(5-(2-ethylhexyl)-4,6-dioxo-5,6-dihydro-4H
      thieno[3,4-c]pyrrol-1-yl)thieno[2',3':5,6]pyrido[3,4-g]thieno[3,2-c]isoquinoline
      5,11(4H,10H)-dione) (PNTPD); poly(5-(4,10-bis(2-butyloctyl)-5,11-dioxo-4,5,10,11
      tetrahydrothieno[2',3':5,6]pyrido[3,4-g]thieno[3,2-c]isoquinolin-2-yl)-2,9-bis(2
      decyldodecyl)anthra[2,1,9-def:6,5,10-d'e'f']diisoquinoline-1,3,8,10(2H,9H)
      tetraone) (PNPDI); and poly(9,9-bis(2-butyloctyl)-9H-fluorene-bis((1,10:5,6)2
      (5,6-dihydro-4H-cyclopenta[b]thiophene-4-ylidene)malonitrile)-2-(2,3
      dihydrothieno[3,4-b][1,4]dioxine)) (PECN)-containing
      thieno[2',3':5',6']pyrido[3,4-g]thieno[3,2-c]isoquinoline-5,11(4H,10H)-dione and
      fluorenedicyclopentathiophene dimalononitrile, were investigated to probe their
      structure-function relationships for solar cell applications. PTB7 was also
      investigated for comparison with the new low-bandgap polymers. The steady-state,
      ultrafast dynamics and nonlinear optical properties of all the organic polymers
      were probed. All the polymers showed broad absorption in the visible region, with
      the absorption of PNPDI and PECN extending into the near-IR region. The polymers
      had HOMO levels ranging from -5.73 to -5.15 eV and low bandgaps of 1.47-2.45 eV.
      Fluorescence upconversion studies on the polymers showed long lifetimes of 1.6
      and 2.4 ns for PNSW and PNTPD, respectively, while PNPDI and PECN showed very
      fast decays within 353 and 110 fs. PECN exhibited a very high two-photon
      absorption cross section. The electronic structure calculations of the repeating
      units of the polymers indicated the localization of the molecular orbitals in
      different co-monomers. As the difference between the electron affinities of the
      co-monomers in the repeating units decreases, the highest occupied and lowest
      unoccupied molecular orbitals become more distributed. All the measurements
      suggest that a large difference in the electron affinities of the co-monomers of
      the polymers contributes to the improvement of the photophysical properties
      necessary for highly efficient solar cell performance. PECN exhibited excellent
      photophysical properties, which makes it to be a good candidate for solar cell
      device applications. 

PMID- 25848674
TI  - A genome-wide analysis of MADS-box genes in peach [Prunus persica (L.) Batsch].
AB  - BACKGROUND: MADS-box genes encode a family of eukaryotic transcription factors
      distinguished by the presence of a highly-conserved ~58 amino acid DNA-binding
      and dimerization domain (the MADS-box). The central role played by MADS-box genes
      in peach endodormancy regulation led us to examine this large gene family in more
      detail. We identified the locations and sequences of 79 MADS-box genes in peach,
      separated them into established subfamilies, and broadly surveyed their tissue
      specific and dormancy-induced expression patterns using next-generation
      sequencing. We then focused on the dormancy-related SVP/AGL24 and FLC
      subfamilies, comparing their numbers and phylogenetic relationships with those of
      other sequenced woody perennial genomes. RESULTS: We identified 79 MADS-box genes
      distributed across all eight peach chromosomes and frequently located in clusters
      of two or more genes. They encode proteins with a mean length of 248 +/- 72 amino
      acids and include representatives from most of the thirteen Type II (MIKC)
      subfamilies, as well as members of the Type I Malpha, Mbeta, and Mgamma
      subfamilies. Most Type I genes were present in species-specific monophyletic
      lineages, and their expression in the peach sporophyte was low or absent. Most
      Type II genes had Arabidopsis orthologs and were expressed at much higher levels
      throughout vegetative and fruit tissues. During short-day-induced growth
      cessation, seven Type II genes from the SVP/AGL24, AGL17, and SEP subfamilies
      showed significant changes in expression. Phylogenetic analyses indicated that
      multiple, independent expansions have taken place within the SVP/AGL24 and FLC
      lineages in woody perennial species. CONCLUSIONS: Most Type I genes appear to
      have arisen through tandem duplications after the divergence of the Arabidopsis
      and peach lineages, whereas Type II genes appear to have increased following
      whole genome duplication events. An exception to the latter rule occurs in the
      FLC and SVP/AGL24 Type II subfamilies, in which species-specific tandem
      duplicates have been retained in a number of perennial species. These subfamilies
      comprise part of a genetic toolkit that regulates endodormancy transitions, but
      phylogenetic and expression data suggest that individual orthologs may not
      function identically across all species.

PMID- 25848676
TI  - Bioactivation of Phytoestrogens: Intestinal Bacteria and Health.
AB  - Phytoestrogens are polyphenols similar to human estrogens found in plants or
      derived from plant precursors. Phytoestrogens are found in high concentration in
      soya, flaxseed and other seeds, fruits, vegetables, cereals, tea, chocolate, etc.
      They comprise several classes of chemical compounds (stilbenes, coumestans,
      isoflavones, ellagitannins, and lignans) which are structurally similar to
      endogenous estrogens but which can have both estrogenic and antiestrogenic
      effects. Although epidemiological and experimental evidence indicates that intake
      of phytoestrogens in foods may be protective against certain chronic diseases,
      discrepancies have been observed between in vivo and in vitro experiments. The
      microbial transformations have not been reported so far in stilbenes and
      coumestans. However, isoflavones, ellagitanins, and lignans are metabolized by
      intestinal bacteria to produce equol, urolithins, and enterolignans,
      respectively. Equol, urolithin, and enterolignans are more bioavailable, and have
      more estrogenic/antiestrogenic and antioxidant activity than their precursors.
      Moreover, equol, urolithins and enterolignans have anti-inflammatory effects and
      induce antiproliferative and apoptosis-inducing activities. The transformation of
      isoflavones, ellagitanins, and lignans by intestinal microbiota is essential to
      be protective against certain chronic diseases, as cancer, cardiovascular
      disease, osteoporosis, and menopausal symptoms. Bioavailability, bioactivity, and
      health effects of dietary phytoestrogens are strongly determined by the
      intestinal bacteria of each individual. 

PMID- 25848677
TI  - Metabolic learning and memory formation by the brain influence systemic metabolic
      homeostasis.
AB  - Metabolic homeostasis is regulated by the brain, but whether this regulation
      involves learning and memory of metabolic information remains unexplored. Here we
      use a calorie-based, taste-independent learning/memory paradigm to show that
      Drosophila form metabolic memories that help in balancing food choice with
      caloric intake; however, this metabolic learning or memory is lost under chronic
      high-calorie feeding. We show that loss of individual learning/memory-regulating
      genes causes a metabolic learning defect, leading to elevated trehalose and lipid
      levels. Importantly, this function of metabolic learning requires not only the
      mushroom body but also the hypothalamus-like pars intercerebralis, while NF
      kappaB activation in the pars intercerebralis mimics chronic overnutrition in
      that it causes metabolic learning impairment and disorders. Finally, we evaluate
      this concept of metabolic learning/memory in mice, suggesting that the
      hypothalamus is involved in a form of nutritional learning and memory, which is
      critical for determining resistance or susceptibility to obesity. In conclusion,
      our data indicate that the brain, and potentially the hypothalamus, direct
      metabolic learning and the formation of memories, which contribute to the control
      of systemic metabolic homeostasis. 

PMID- 25848678
TI  - Platelet-Rich Plasma Prolongs Myofibroblast Accumulation in Corneal Stroma with
      Incisional Wound.
AB  - PURPOSE: The purpose of this study was to determine whether platelet-rich plasma
      (PRP) has an effect on corneal stromal cells in a rat model of wound healing
      following corneal incision. MATERIALS AND METHODS: The effect of PRP on corneal
      wound healing in vivo was investigated in a corneal incision wound model in rats.
      40 rats were wounded by deep corneal incision, and treated with either topically
      administered PRP (20 rats) or sodium chloride (20 rats). At 4 h and 1, 3, and 5
      days after incision, alpha-smooth muscle actin (alpha SMA), SMAD2 and SMAD3
      expression and apoptosis in stromal cells were evaluated by immunohistochemistry,
      and IL-1beta mRNA expression was evaluated by real time PCR. RESULTS: PRP-treated
      corneas exhibited reduced stromal cell apoptosis at day 3 and day 5 (p = 0.038,
      and <0.001, respectively) relative to controls. Interleukin-1beta mRNA
      expression, however, was unchanged in PRP-treated corneas relative to controls.
      Topical PRP treatment resulted in a higher proportion of alphaSMA-positive
      myofibroblasts recruited to the wound site relative to control corneas. PRP did
      not affect activation of SMAD2 but activation of SMAD3 was significantly reduced
      at day 1 (p = 0.001) and dramatically increased at day 5 (p = 0.032).
      CONCLUSIONS: PRP treatment resulted in suppressed stromal cell apoptosis followed
      by SMAD3 activation and a greater proportion of myofibroblasts present at the
      wound site. Suppression of stromal cell apoptosis after corneal wounding by use
      of a growth factor-rich formulation may lead to myofibroblast accumulation by
      modulation of the TGF-beta pathway.

PMID- 25848679
TI  - Enhanced Reactivity in Hydrogen Atom Transfer from Tertiary Sites of Cyclohexanes
      and Decalins via Strain Release: Equatorial C-H Activation vs Axial C-H
      Deactivation.
AB  - Absolute rate constants for hydrogen atom transfer (HAT) from cycloalkanes and
      decalins to the cumyloxyl radical (CumO(*)) were measured by laser flash
      photolysis. Very similar reactivities were observed for the C-H bonds of
      cyclopentane and cyclohexane, while the tertiary C-H bond of methylcyclopentane
      was found to be 6 times more reactive than the tertiary axial C-H bond of
      methylcyclohexane, pointing toward a certain extent of tertiary axial C-H bond
      deactivation. Comparison between the cis and trans isomers of 1,2
      dimethylcyclohexane, 1,4-dimethylcyclohexane and decalin provides a quantitative
      evaluation of the role played by strain release in these reactions. kH values for
      HAT from tertiary equatorial C-H bonds were found to be at least 1 order of
      magnitude higher than those for HAT from the corresponding tertiary axial C-H
      bonds (kH(eq)/kH(ax) = 10-14). The higher reactivity of tertiary equatorial C-H
      bonds was explained in terms of 1,3-diaxial strain release in the HAT transition
      state. Increase in torsional strain in the HAT transition state accounts instead
      for tertiary axial C-H bond deactivation. The results are compared with those
      obtained for the corresponding C-H functionalization reactions by dioxiranes and
      nonheme metal-oxo species indicating that CumO(*) can represent a convenient
      model for the reactivity patterns of these oxidants. 

PMID- 25848680
TI  - Chronic exposure of diesel exhaust particles induces alveolar enlargement in
      mice.
AB  - BACKGROUND: Diesel exhaust particles (DEPs) are deposited into the respiratory
      tract and are thought to be a risk factor for the development of diseases of the
      respiratory system. In healthy individuals, the timing and mechanisms of
      respiratory tract injuries caused by chronic exposure to air pollution remain to
      be clarified. METHODS: We evaluated the effects of chronic exposure to DEP at
      doses below those found in a typical bus corridor in Sao Paulo (150 MUg/m3). Male
      BALB/c mice were divided into mice receiving a nasal instillation: saline
      (saline; n = 30) and 30 MUg/10 MUL of DEP (DEP; n = 30). Nasal instillations were
      performed five days a week, over a period of 90 days. Bronchoalveolar lavage
      (BAL) was performed, and the concentrations of interleukin (IL)-4, IL-10, IL-13
      and interferon-gamma (INF-gamma) were determined by ELISA-immunoassay. Assessment
      of respiratory mechanics was performed. The gene expression of Muc5ac in lung was
      evaluated by RT-PCR. The presence of IL-13, MAC2+ macrophages, CD3+, CD4+, CD8+ T
      cells and CD20+ B cells in tissues was analysed by immunohistochemistry.
      Bronchial thickness and the collagen/elastic fibers density were evaluated by
      morphometry. We measured the mean linear intercept (Lm), a measure of alveolar
      distension, and the mean airspace diameter (D0) and statistical distribution
      (D2). RESULTS: DEP decreased IFN-gamma levels in BAL (p = 0.03), but did not
      significantly alter IL-4, IL-10 and IL-13 levels. MAC2+ macrophage, CD4+ T cell
      and CD20+ B cell numbers were not altered; however, numbers of CD3+ T cells (p <=
      0.001) and CD8+ T cells (p <= 0.001) increased in the parenchyma. Although IL-13
      (p = 0.008) expression decreased in the bronchiolar epithelium, Muc5ac gene
      expression was not altered in the lung of DEP-exposed animals. Although
      respiratory mechanics, elastic and collagen density were not modified, the mean
      linear intercept (Lm) was increased in the DEP-exposed animals (p <= 0.001), and
      the index D2 was statistically different (p = 0.038) from the control animals.
      CONCLUSION: Our data suggest that nasal instillation of low doses of DEP over a
      period of 90 days results in alveolar enlargement in the pulmonary parenchyma of
      healthy mice.

PMID- 25848682
TI  - Read My Lips: Brain Dynamics Associated with Audiovisual Integration and Deviance
      Detection.
AB  - Information from different modalities is initially processed in different brain
      areas, yet real-world perception often requires the integration of multisensory
      signals into a single percept. An example is the McGurk effect, in which people
      viewing a speaker whose lip movements do not match the utterance perceive the
      spoken sounds incorrectly, hearing them as more similar to those signaled by the
      visual rather than the auditory input. This indicates that audiovisual
      integration is important for generating the phoneme percept. Here we asked when
      and where the audiovisual integration process occurs, providing spatial and
      temporal boundaries for the processes generating phoneme perception.
      Specifically, we wanted to separate audiovisual integration from other processes,
      such as simple deviance detection. Building on previous work employing ERPs, we
      used an oddball paradigm in which task-irrelevant audiovisually deviant stimuli
      were embedded in strings of non-deviant stimuli. We also recorded the event
      related optical signal, an imaging method combining spatial and temporal
      resolution, to investigate the time course and neuroanatomical substrate of
      audiovisual integration. We found that audiovisual deviants elicit a short
      duration response in the middle/superior temporal gyrus, whereas audiovisual
      integration elicits a more extended response involving also inferior frontal and
      occipital regions. Interactions between audiovisual integration and deviance
      detection processes were observed in the posterior/superior temporal gyrus. These
      data suggest that dynamic interactions between inferior frontal cortex and
      sensory regions play a significant role in multimodal integration. 

PMID- 25848681
TI  - "The Cooties Effect": Amygdala Reactivity to Opposite- versus Same-sex Faces
      Declines from Childhood to Adolescence.
AB  - One of the most important social identities that children learn to define
      themselves and others by is sex, becoming a salient social category by early
      childhood. Although older children begin to show greater flexibility in their
      gendered behaviors and attitudes, gender rigidity intensifies again around the
      time of puberty. In the current study, we assessed behavioral and neural biases
      to sex across a wide age group. Ninety-three youth (ages 7-17 years) provided
      behavioral rating of same- and opposite-sex attitudes, and 52 youth (ages 4-18
      years) underwent an fMRI scan as they matched the emotion of same- and opposite
      sex faces. We demonstrate significant age-related behavioral biases of sex that
      are mediated by differential amygdala response to opposite-sex relative to same
      sex faces in children, an effect that completely attenuates by the teenage years.
      Moreover, we find a second peak in amygdala sensitivity to opposite-sex faces
      around the time of puberty. Thus, the amygdala codes for developmentally
      dependent and motivationally relevant social identification across development. 

PMID- 25848683
TI  - Early Visual Word Processing Is Flexible: Evidence from Spatiotemporal Brain
      Dynamics.
AB  - Visual word recognition is often described as automatic, but the functional locus
      of top-down effects is still a matter of debate. Do task demands modulate how
      information is retrieved, or only how it is used? We used EEG/MEG recordings to
      assess whether, when, and how task contexts modify early retrieval of specific
      psycholinguistic information in occipitotemporal cortex, an area likely to
      contribute to early stages of visual word processing. Using a parametric
      approach, we analyzed the spatiotemporal response patterns of occipitotemporal
      cortex for orthographic, lexical, and semantic variables in three
      psycholinguistic tasks: silent reading, lexical decision, and semantic decision.
      Task modulation of word frequency and imageability effects occurred
      simultaneously in ventral occipitotemporal regions-in the vicinity of the
      putative visual word form area-around 160 msec, following task effects on
      orthographic typicality around 100 msec. Frequency and typicality also produced
      task-independent effects in anterior temporal lobe regions after 200 msec. The
      early task modulation for several specific psycholinguistic variables indicates
      that occipitotemporal areas integrate perceptual input with prior knowledge in a
      task-dependent manner. Still, later task-independent effects in anterior temporal
      lobes suggest that word recognition eventually leads to retrieval of semantic
      information irrespective of task demands. We conclude that even a highly
      overlearned visual task like word recognition should be described as flexible
      rather than automatic. 

PMID- 25848684
TI  - Rapid Context-based Identification of Target Sounds in an Auditory Scene.
AB  - To make sense of our dynamic and complex auditory environment, we must be able to
      parse the sensory input into usable parts and pick out relevant sounds from all
      the potentially distracting auditory information. Although it is unclear exactly
      how we accomplish this difficult task, Gamble and Woldorff [Gamble, M. L., &
      Woldorff, M. G. The temporal cascade of neural processes underlying target
      detection and attentional processing during auditory search. Cerebral Cortex (New
      York, N.Y.: 1991), 2014] recently reported an ERP study of an auditory target
      search task in a temporally and spatially distributed, rapidly presented,
      auditory scene. They reported an early, differential, bilateral activation
      (beginning at 60 msec) between feature-deviating target stimuli and physically
      equivalent feature-deviating nontargets, reflecting a rapid target detection
      process. This was followed shortly later (at 130 msec) by the lateralized N2ac
      ERP activation, that reflects the focusing of auditory spatial attention toward
      the target sound and parallels the attentional-shifting processes widely studied
      in vision. Here we directly examined the early, bilateral, target-selective
      effect to better understand its nature and functional role. Participants listened
      to midline-presented sounds that included target and nontarget stimuli that were
      randomly either embedded in a brief rapid stream or presented alone. The results
      indicate that this early bilateral effect results from a template for the target
      that utilizes its feature deviancy within a stream to enable rapid
      identification. Moreover, individual-differences analysis showed that the size of
      this effect was larger for participants with faster RTs. The findings support the
      hypothesis that our auditory attentional systems can implement and utilize a
      context-based relational template for a target sound, making use of additional
      auditory information in the environment when needing to rapidly detect a relevant
      sound. 

PMID- 25848685
TI  - Multivariate fMRI and Eye Tracking Reveal Differential Effects of Visual
      Interference on Recognition Memory Judgments for Objects and Scenes.
AB  - Recent work has demonstrated that the perirhinal cortex (PRC) supports
      conjunctive object representations that aid object recognition memory following
      visual object interference. It is unclear, however, how these representations
      interact with other brain regions implicated in mnemonic retrieval and how
      congruent and incongruent interference influences the processing of targets and
      foils during object recognition. To address this, multivariate partial least
      squares was applied to fMRI data acquired during an interference match-to-sample
      task, in which participants made object or scene recognition judgments after
      object or scene interference. This revealed a pattern of activity sensitive to
      object recognition following congruent (i.e., object) interference that included
      PRC, prefrontal, and parietal regions. Moreover, functional connectivity analysis
      revealed a common pattern of PRC connectivity across interference and recognition
      conditions. Examination of eye movements during the same task in a separate study
      revealed that participants gazed more at targets than foils during correct object
      recognition decisions, regardless of interference congruency. By contrast,
      participants viewed foils more than targets for incorrect object memory
      judgments, but only after congruent interference. Our findings suggest that
      congruent interference makes object foils appear familiar and that a network of
      regions, including PRC, is recruited to overcome the effects of interference. 

PMID- 25848686
TI  - Mass and Charge Transport in the Polymer-Ionic-Liquid System PEO-EMImI: From
      Ionic-Liquid-in-Polymer to Polymer-in-Ionic-Liquid Electrolytes.
AB  - Conventional polymer electrolytes based on inorganic salts are commonly
      characterized and utilized over a small salt-poor composition range because of
      phase transitions accompanied by loss of ion conductivity at high salt
      concentrations. By contrast, well-chosen polymer-ionic-liquid (IL) systems offer
      the possibility to vary the IL content from the IL-in-polymer to the polymer-in
      IL domain. We have investigated the temperature-dependent ionic conductivity in
      PEOyEMImI systems consisting of poly(ethylene oxide) complexed with 1-ethyl-3
      methylimidazolium iodide for y = EO/IL ratios ranging from 0.6 to 60 and compared
      diffusivity data with that arising from (1)H pulsed-field-gradient nuclear
      magnetic resonance for EMIm and (125)I radiotracer diffusion for iodine.
      Surprisingly, the diffusivity of cations and anions vary at most by 50% at fixed
      temperatures over the entire composition range. The much larger changes in the
      charge diffusivity Dsigma relate to ion pairing exhibiting a minimum near the
      intermediate composition y = 10. Altogether, the results are relevant to
      application in dye-sensitized solar cells and show that a high ion density is
      crucial to enhance the iodine transport capacity. 

PMID- 25848688
TI  - Studies on formation, control and application of biofilm formed by food related
      microorganisms.
AB  - Biofilms are sessile microbial aggregates on the interfaces, and they were
      usually considered as microbial contamination sources in medical care and various
      industries. We studied the control and application of biofilms formed by food
      related microorganisms, and mechanism of the biofilm formation was also
      investigated. We studied the biofilm formation in mixed cultures using various
      combinations of two strains of food-related microorganisms. There were various
      microorganisms that showed decreased or increased biofilm formation in the mixed
      culture in comparison with that in a single culture. Biofilm formed by lactic
      acid bacteria and yeast isolated from traditional fermented food, Fukuyama pot
      vinegar, exhibited unique feature in that structure and formation mechanism, and
      expected to be used as an immobilized microorganism in fermentation production.
      Here our studies on the control and application of biofilms and the mechanisms of
      its formation were described. 

PMID- 25848687
TI  - Comparative metabolic and transcriptional analysis of a doubled diploid and its
      diploid citrus rootstock (C. junos cv. Ziyang xiangcheng) suggests its potential
      value for stress resistance improvement.
AB  - BACKGROUND: Polyploidy has often been considered to confer plants a better
      adaptation to environmental stresses. Tetraploid citrus rootstocks are expected
      to have stronger stress tolerance than diploid. Plenty of doubled diploid citrus
      plants were exploited from diploid species for citrus rootstock improvement.
      However, limited metabolic and molecular information related to tetraploidization
      is currently available at a systemic biological level. This study aimed to
      evaluate the occurrence and extent of metabolic and transcriptional changes
      induced by tetraploidization in Ziyang xiangcheng (Citrus junos Sieb. ex Tanaka),
      which is a special citrus germplasm native to China and widely used as an iron
      deficiency tolerant citrus rootstock. RESULTS: Doubled diploid Ziyang xiangcheng
      has typical morphological and anatomical features such as shorter plant height,
      larger and thicker leaves, bigger stomata and lower stomatal density, compared to
      its diploid parent. GC-MS (Gas chromatography coupled to mass spectrometry)
      analysis revealed that tetraploidization has an activation effect on the
      accumulation of primary metabolites in leaves; many stress-related metabolites
      such as sucrose, proline and gamma-aminobutyric acid (GABA) was remarkably up
      regulated in doubled diploid. However, LC-QTOF-MS (Liquid chromatography
      quadrupole time-of-flight mass spectrometry) analysis demonstrated that
      tetraploidization has an inhibition effect on the accumulation of secondary
      metabolites in leaves; all the 33 flavones were down-regulated while all the 6
      flavanones were up-regulated in 4x. By RNA-seq analysis, only 212 genes (0.8% of
      detected genes) are found significantly differentially expressed between 2x and
      4x leaves. Notably, those genes were highly related to stress-response functions,
      including responses to salt stress, water and abscisic acid. Interestingly, the
      transcriptional divergence could not explain the metabolic changes, probably due
      to post-transcriptional regulation. CONCLUSION: Taken together, tetraploidization
      induced considerable changes in leaf primary and secondary metabolite
      accumulation in Ziyang xiangcheng. However, the effect of tetraploidization on
      transcriptome is limited. Compared to diploid, higher expression level of stress
      related genes and higher content of stress related metabolites in doubled diploid
      could be beneficial for its stress tolerance.

PMID- 25848689
TI  - Genetic mapping of centromeres in the nine Citrus clementina chromosomes using
      half-tetrad analysis and recombination patterns in unreduced and haploid gametes.
AB  - BACKGROUND: Mapping centromere locations in plant species provides essential
      information for the analysis of genetic structures and population dynamics. The
      centromere's position affects the distribution of crossovers along a chromosome
      and the parental heterozygosity restitution by 2n gametes is a direct function of
      the genetic distance to the centromere. Sexual polyploidisation is relatively
      frequent in Citrus species and is widely used to develop new seedless triploid
      cultivars. The study's objectives were to (i) map the positions of the
      centromeres of the nine Citrus clementina chromosomes; (ii) analyse the crossover
      interference in unreduced gametes; and (iii) establish the pattern of genetic
      recombination in haploid clementine gametes along each chromosome and its
      relationship with the centromere location and distribution of genic sequences.
      RESULTS: Triploid progenies were derived from unreduced megagametophytes produced
      by second-division restitution. Centromere positions were mapped genetically for
      all linkage groups using half-tetrad analysis. Inference of the physical
      locations of centromeres revealed one acrocentric, four metacentric and four
      submetacentric chromosomes. Crossover interference was observed in unreduced
      gametes, with variation seen between chromosome arms. For haploid gametes, a
      strong decrease in the recombination rate occurred in centromeric and
      pericentromeric regions, which contained a low density of genic sequences. In
      chromosomes VIII and IX, these low recombination rates extended beyond the
      pericentromeric regions. The genomic region corresponding to a genetic distance <
      5cM from a centromere represented 47% of the genome and 23% of the genic
      sequences. CONCLUSIONS: The centromere positions of the nine citrus chromosomes
      were genetically mapped. Their physical locations, inferred from the genetic
      ones, were consistent with the sequence constitution and recombination pattern
      along each chromosome. However, regions with low recombination rates extended
      beyond the pericentromeric regions of some chromosomes into areas richer in genic
      sequences. The persistence of strong linkage disequilibrium between large numbers
      of genes promotes the stability of epistatic interactions and multilocus
      controlled traits over successive generations but also maintains multi-trait
      associations. Identification of the centromere positions will allow the
      development of simple methods to analyse unreduced gamete formation mechanisms in
      a large range of genotypes and further modelling of genetic inheritance in sexual
      polyploidisation breeding schemes.

PMID- 25848691
TI  - Functional Characterization of Long Noncoding RNA Lnc_bc060912 in Human Lung
      Carcinoma Cells.
AB  - Long noncoding RNAs (lncRNAs) are pervasively transcribed in the human genome.
      Recent studies suggest that the involvement of lncRNAs in human diseases could be
      far more prevalent than previously appreciated. Here we have identified a lncRNA
      termed Lnc_bc060912 whose expression is increased in human lung and other tumors.
      Lnc_bc060912 is 1.2 kb in length and is composed of two exons. The expression of
      Lnc_bc060912 was repressed by p53. Lnc_bc060912 suppressed cell apoptosis. Using
      a recently developed method for RNA-pulldown with formaldehyde cross-linking, we
      found that Lnc_bc060912 interacted with the two DNA damage repair proteins PARP1
      and NPM1. Together, these results suggest that Lnc_bc060912, via PARP1 and NPM1,
      affects cell apoptosis and may play important roles in tumorigenesis and cancer
      progression.

PMID- 25848690
TI  - The OsSec18 complex interacts with P0(P1-P2)2 to regulate vacuolar morphology in
      rice endosperm cell.
AB  - BACKGROUND: Sec18p/N-ethylmaleimide-sensitive factor (NSF) is a conserved
      eukaryotic ATPase, which primarily functions in vesicle membrane fusion from
      yeast to human. However, the function of the OsSec18 gene, a homologue of NSF in
      rice, remains unknown. RESULTS: In the present study, we investigated the
      function of OsSec18 in rice and found that OsSec18 complements the temperature
      sensitive phenotype and interferes with vacuolar morphogenesis in yeast.
      Overexpression of OsSec18 in rice decreased the plant height and 1000-grain
      weight and altered the morphology of the protein bodies. Further examination
      revealed that OsSec18 presented as a 290-kDa complex in rice endosperm cells.
      Moreover, Os60sP0 was identified a component of this complex, demonstrating that
      the OsSec18 complex contains another complex of P0(P1-P2)2 in rice endosperm
      cells. Furthermore, we determined that the N-terminus of OsSec18 can interact
      with the N- and C-termini of Os60sP0, whereas the C-terminus of OsSec18 can only
      interact with the C-terminus of Os60sP0. CONCLUSION: Our results revealed that
      the OsSec18 regulates vacuolar morphology in both yeast and rice endosperm cell
      and the OsSec18 interacts with P0(P1-P2)2 complex in rice endosperm cell.

PMID- 25848692
TI  - The economic impact of rapid Candida species identification by T2Candida among
      high-risk patients.
AB  - INTRODUCTION: This study estimates the cost-effectiveness and hospital budget
      impact of rapid candidemia identification using T2Candida, a novel diagnostic
      panel with same-day species-specific results. MATERIALS & METHODS: A 1-year
      decision-tree model estimates hospital costs (2013 US$) and effects (candidemia
      related deaths) for faster diagnostics versus blood culture (BC), accounting for
      disease prevalence, distribution of Candida species, test characteristics
      (sensitivity/specificity/time to result), antifungal medication and differential
      length-of-stay and mortality by appropriate treatment timing. RESULTS: The model
      estimates a hospital with 5100 annual high-risk patients could possibly save
      $5,858,448 with T2Candida versus BC, a 47.6% decrease in candidemia diagnosis and
      treatment budget ($1149/patient tested), while averting 60.6% of candidemia
      related mortality. CONCLUSION: Hospitals may observe lower candidemia-related
      inpatient costs and mortality with rapid Candida diagnosis.

PMID- 25848693
TI  - Daring to Marry: Marriage Equality Activism After Proposition 8 as Challenge to
      the Assimilationist/Radical Binary in Queer Studies.
AB  - I analyze three case studies of marriage equality activism and marriage equality
      based groups after the passage of Proposition 8 in California. Evaluating the
      JoinTheImpact protests of 2008, the LGBTQ rights group GetEQUAL, and the group
      One Struggle One Fight, I argue that these groups revise queer theoretical
      arguments about marriage equality activism as by definition assimilationist,
      homonormative, and single-issue. In contrast to such claims, the cases studied
      here provide a snapshot of heterogeneous, intersectional, and coalition-based
      social justice work in which creative methods of protest, including direct action
      and flash mobs, are deployed in militant ways for marriage rights and beyond.

PMID- 25848694
TI  - Saccharomyces cerevisiae cell wall components as tools for ochratoxin a
      decontamination.
AB  - The aim of this study was to evaluate the usefulness of Saccharomyces cerevisiae
      cell wall preparations in the adsorption of ochratoxin A (OTA). The study
      involved the use of a brewer's yeast cell wall devoid of protein substances,
      glucans obtained by water and alkaline extraction, a glucan commercially
      available as a dietary supplement for animals and, additionally, dried brewer's
      yeast for comparison. Fourier Transform Infrared (FTIR) analysis of the obtained
      preparations showed bands characteristic for glucans in the resulting spectra.
      The yeast cell wall preparation, water-extracted glucan and the commercial glucan
      bound the highest amount of ochratoxin A, above 55% of the initial concentration,
      and the alkaline-extracted glucan adsorbed the lowest amount of this toxin. It
      has been shown that adsorption is most effective at a close-to-neutral pH, while
      being considerably limited in alkaline conditions.

PMID- 25848695
TI  - Ras/MEK/MAPK-mediated regulation of heparin sulphate proteoglycans promotes
      retinal fate in the Drosophila eye-antennal disc.
AB  - Generating cellular heterogeneity is crucial to the development of complex
      organs. Organ-fate selector genes and signalling pathways generate cellular
      diversity by subdividing and patterning naive tissues to assign them regional
      identities. The Drosophila eye-antennal imaginal disc is a well-characterised
      system in which to study regional specification; it is first divided into
      antennal and eye fates and subsequently retinal differentiation occurs within
      only the eye field. During development, signalling pathways and selector genes
      compete with and mutually antagonise each other to subdivide the tissue. Wingless
      (Wg) signalling is the main inhibitor of retinal differentiation; it does so by
      promoting antennal/head-fate via selector factors and by antagonising Hedgehog
      (Hh), the principal differentiation-initiating signal. Wg signalling must be
      suppressed by JAK/STAT at the disc posterior in order to initiate retinal
      differentiation. Ras/MEK/MAPK signalling has also been implicated in initiating
      retinal differentiation but its mode of action is not known. We find that
      compromising Ras/MEK/MAPK signalling in the early larval disc results in expanded
      antennal/head cuticle at the expense of the compound eye. These phenotypes
      correspond both to perturbations in selector factor expression, and to de
      repressed wg. Indeed, STAT activity is reduced due to decreased mobility of the
      ligand Unpaired (Upd) along with a corresponding loss in Dally-like protein
      (Dlp), a heparan sulphate proteoglycan (HSPG) that aids Upd diffusion.
      Strikingly, blocking HSPG biogenesis phenocopies compromised Ras/MEK/MAPK, while
      restoring HSPG expression rescues the adult phenotype significantly. This study
      identifies a novel mode by which the Ras/MEK/MAPK pathway regulates regional-fate
      specification via HSPGs during development. 

PMID- 25848696
TI  - ATP4a is required for development and function of the Xenopus mucociliary
      epidermis - a potential model to study proton pump inhibitor-associated
      pneumonia.
AB  - Proton pump inhibitors (PPIs), which target gastric H(+)/K(+)ATPase (ATP4), are
      among the most commonly prescribed drugs. PPIs are used to treat ulcers and as a
      preventative measure against gastroesophageal reflux disease in hospitalized
      patients. PPI treatment correlates with an increased risk for airway infections,
      i.e. community- and hospital-acquired pneumonia. The cause for this correlation,
      however, remains elusive. The Xenopus embryonic epidermis is increasingly being
      used as a model to study airway-like mucociliary epithelia. Here we use this
      model to address how ATP4 inhibition may affect epithelial function in human
      airways. We demonstrate that atp4a knockdown interfered with the generation of
      cilia-driven extracellular fluid flow. ATP4a and canonical Wnt signaling were
      required in the epidermis for expression of foxj1, a transcriptional regulator of
      motile ciliogenesis. The ATP4/Wnt module activated foxj1 downstream of ciliated
      cell fate specification. In multiciliated cells (MCCs) of the epidermis, ATP4a
      was also necessary for normal myb expression, apical actin formation, basal body
      docking and alignment of basal bodies. Furthermore, ATP4-dependent Wnt/beta
      catenin signaling in the epidermis was a prerequisite for foxa1-mediated
      specification of small secretory cells (SSCs). SSCs release serotonin and other
      substances into the medium, and thereby regulate ciliary beating in MCCs and
      protect the epithelium against infection. Pharmacological inhibition of ATP4 in
      the mature mucociliary epithelium also caused a loss of MCCs and led to impaired
      mucociliary clearance. These data strongly suggest that PPI-associated pneumonia
      in human patients might, at least in part, be linked to dysfunction of
      mucociliary epithelia of the airways.

PMID- 25848698
TI  - The impact of hepatitis B virus (HBV) infection on clinical outcomes of patients
      with diffuse large B-cell lymphoma.
AB  - We performed a retrospective study to analyse the characteristics and clinical
      outcomes of diffuse large B-cell lymphoma (DLBCL) patients with hepatitis B virus
      (HBV) infection and compare with those without HBV infection. The occurrence of
      hepatitis after withdrawal of prophylactic antiviral treatment on completion of
      chemotherapy was also assessed. The HBsAg-positive patients were given
      prophylactic antiviral treatment until 6 months after finishing chemotherapy. A
      total of 81 patients were recruited with 16 in the HBsAg-positive group and 65 in
      the HBsAg-negative group. The clinical characteristics were similar in both
      groups of patients. There was no significant difference in complete remission
      rate between the two groups (63% in HBsAg-positive group vs. 54% in HBsAg
      negative group, P = 0.59). There was also no statistically significant difference
      in overall survival between the two groups (P = 0.23). Four of the 16 HBsAg
      positive patients (25%) had hepatitis after cessation of chemotherapy and
      prophylactic lamivudine. The mean time of onset of hepatitis was 3 months after
      stopping lamivudine. In conclusion, HBV infection did not appear to affect the
      prognosis of DLBCL patients given antiviral prophylaxis. It is reasonable to
      consider prophylactic antiviral therapy to extend to at least one year on
      completion of chemotherapy. 

PMID- 25848697
TI  - Distinct structural requirements for CDON and BOC in the promotion of Hedgehog
      signaling.
AB  - Proper levels of Hedgehog (HH) signaling are essential during embryonic
      development and adult tissue homeostasis. A central mechanism to control HH
      pathway activity is through the regulation of secreted HH ligands at the plasma
      membrane. Recent studies have revealed a collective requirement for the cell
      surface co-receptors GAS1, CDON and BOC in HH signal transduction. Despite their
      requirement in HH pathway function, the mechanisms by which these proteins act to
      promote HH signaling remain poorly understood. Here we focus on the function of
      the two structurally related co-receptors, CDON and BOC. We utilized an in vivo
      gain-of-function approach in the developing chicken spinal cord to dissect the
      structural requirements for CDON and BOC function in HH signal transduction.
      Notably, we find that although CDON and BOC display functional redundancy during
      HH-dependent ventral neural patterning, these molecules utilize distinct
      molecular mechanisms to execute their HH-promoting effects. Specifically, we
      define distinct membrane attachment requirements for CDON and BOC function in HH
      signal transduction. Further, we identify novel and separate extracellular motifs
      in CDON and BOC that are required to promote HH signaling. Together, these data
      suggest that HH co-receptors employ distinct mechanisms to mediate HH pathway
      activity. 

PMID- 25848699
TI  - Awareness, treatment and control of cardiometabolic disorders in Chinese adults
      with diabetes: a national representative population study.
AB  - BACKGROUND: The diagnosis of diabetes has important clinic implications for the
      prevention and management of cardiometabolic disorders. We aimed to investigate
      the awareness, treatment and control of hypertension and dyslipidemia in
      previously-diagnosed and newly-diagnosed diabetes in Chinese adult population.
      METHODS: We conducted a cross-sectional survey in a nationally representative
      sample of 98658 Chinese adults aged 18 years or older in 2010, using a complex,
      multistage, probability sampling design. Glycemic status were defined according
      to the 2010 American Diabetes Association criteria. Hypertension was diagnosed by
      the Seventh Report of the Joint National Committee on Prevention, Detection,
      Evaluation, and Treatment of High Blood Pressure. Dyslipidemia was diagnosed by
      the 2004 National Cholesterol Education Program Adult Treatment Panel III.
      RESULTS: The weighted prevalence of hypertension and dyslipidemia gradually
      increased in adults with normal glucose regulation, prediabetes, newly-diagnosed
      diabetes and previously-diagnosed diabetes. Compared to newly-diagnosed diabetes
      patients, previously-diagnosed diabetes patients were more likely to be aware of
      hypertension (weighted percentage [95% confidence interval]: 55.2% [52.9%-57.5%]
      vs 37.6% [35.9%-39.3%]) and dyslipidemia (33.9% [31.8%-36.1%] vs 12.8% [11.7%
      13.9%]), to receive blood pressure-lowing (43.7% [41.5%-46.0%] vs 27.5% [26.0%
      29.0%]) and lipid-lowering (18.9% [17.2%-20.7%] vs 5.4% [4.6%-6.2%]) therapies,
      and to have controlled blood pressure (4.7% [3.5%-6.2%] vs 3.5% [2.6%-4.8%]) and
      lipid (15.9% [12.3%-20.3%] vs 9.5% [6.4%-13.8%]) levels. CONCLUSIONS: Detection
      and control of hypertension and dyslipidemia is far from optimal in Chinese
      adults, especially in newly-diagnosed diabetes. Improved screening for diabetes
      is required to promote a better prevention, treatment and control of hypertension
      and dyslipidemia in China.

PMID- 25848700
TI  - In silico discovery and validation of potent small-molecule inhibitors targeting
      the activation function 2 site of human oestrogen receptor alpha.
AB  - INTRODUCTION: Current approaches to inhibit oestrogen receptor-alpha (ERalpha)
      are focused on targeting its hormone-binding pocket and have limitations. Thus,
      we propose that inhibitors that bind to a coactivator-binding pocket on ERalpha,
      called activation function 2 (AF2), might overcome some of these limitations.
      METHODS: In silico virtual screening was used to identify small-molecule ERalpha
      AF2 inhibitors. These compounds were screened for inhibition of ERalpha
      transcriptional activity using stably transfected T47D-KBluc cell line. A direct
      physical interaction between the AF2 binders and the ERalpha protein was measured
      using biolayer interferometry (BLI) and an ERalpha coactivator displacement
      assay. Cell viability was assessed by MTS assay in ERalpha-positive MCF7 cells,
      tamoxifen-resistant (TamR) cell lines TamR3 and TamR6, and ERalpha-negative MDA
      MB-453 and HeLa cell lines. In addition, ERalpha inhibition in TamR cells and the
      effect of compounds on mRNA and protein expression of oestrogen-dependent genes,
      pS2, cathepsin D and cell division cycle 2 (CDC2) were determined. RESULTS:
      Fifteen inhibitors from two chemical classes, derivatives of pyrazolidine-3,5
      dione and carbohydrazide, were identified. In a series of in vitro assays, VPC
      16230 of the carbohydrazide chemical class emerged as a lead ERalpha AF2
      inhibitor that significantly downregulated ERalpha transcriptional activity (half
      maximal inhibitory concentration = 5.81 MUM). By directly binding to the ERalpha
      protein, as confirmed by BLI, VPC-16230 effectively displaced coactivator
      peptides from the AF2 pocket, confirming its site-specific action. VPC-16230
      selectively suppressed the growth of ERalpha-positive breast cancer cells.
      Furthermore, it significantly inhibited ERalpha mediated transcription in TamR
      cells. More importantly, it reduced mRNA and protein levels of pS2, cathepsin D
      and CDC2, validating its ER-directed activity. CONCLUSION: We identified VPC
      16230 as an ERalpha AF2-specific inhibitor that demonstrated promising
      antiproliferative effects in breast cancer cell lines, including TamR cells. VPC
      16230 reduced the expression of ERalpha-inducible genes, including CDC2, which is
      involved in cell division. We anticipate that the application of ERalpha AF2
      inhibitors will provide a novel approach that can act as a complementary
      therapeutic to treat ERalpha-positive, tamoxifen-resistant and metastatic breast
      cancers.

PMID- 25848701
TI  - Individual and psychosocial mechanisms of adaptive functioning in parentally
      bereaved children.
AB  - The authors examined factors theorized to contribute to adaptive functioning in
      56 parentally bereaved children (age 7-13) who had lost their caregiver within
      the previous 6 months. Adaptive functioning, defined as falling below clinical
      threshold levels on all measures of depression, posttraumatic stress, anxiety,
      and internalizing/externalizing symptoms, characterized 57% of the sample. Linear
      mixed modeling revealed that children in the adaptive functioning group had lower
      mean scores on avoidant coping and higher mean scores on coping efficacy,
      religiosity, parental positive reinforcement, and parental empathy. Findings
      suggest that adaptive functioning following parental loss is related to both
      child-intrinsic factors and child-extrinsic factors. 

PMID- 25848702
TI  - Ginger-Mechanism of action in chemotherapy-induced nausea and vomiting: A review.
AB  - Despite advances in antiemetic therapy, chemotherapy-induced nausea and vomiting
      (CINV) still poses a significant burden to patients undergoing chemotherapy.
      Nausea, in particular, is still highly prevalent in this population. Ginger has
      been traditionally used as a folk remedy for gastrointestinal complaints and has
      been suggested as a viable adjuvant treatment for nausea and vomiting in the
      cancer context. Substantial research has revealed ginger to possess properties
      that could exert multiple beneficial effects on chemotherapy patients who
      experience nausea and vomiting. Bioactive compounds within the rhizome of ginger,
      particularly the gingerol and shogaol class of compounds, interact with several
      pathways that are directly implicated in CINV in addition to pathways that could
      play secondary roles by exacerbating symptoms. These properties include 5-HT3,
      substance P, and acetylcholine receptor antagonism; antiinflammatory properties;
      and modulation of cellular redox signaling, vasopressin release, gastrointestinal
      motility, and gastric emptying rate. This review outlines these proposed
      mechanisms by discussing the results of clinical, in vitro, and animal studies
      both within the chemotherapy context and in other relevant fields. The evidence
      presented in this review indicates that ginger possesses multiple properties that
      could be beneficial in reducing CINV.

PMID- 25848703
TI  - Acute effects of caffeine supplementation on cortical arousal, anxiety,
      physiological response and marksmanship in close quarter combat.
AB  - Previous studies have researched the ergogenic effect of caffeine in different
      shooting actions, but none of them in a stressful combat action. This study aimed
      to analyse the effect of a dose of 400 mg of caffeine monohydrate on the psycho
      physiological response and marksmanship of soldiers in close quarter combat
      (CQC). We analysed the heart rate, blood lactate concentration, cortical arousal,
      state anxiety and marksmanship of 19 soldiers in the Spanish Army (38.9 +/- 4.1
      years; 177.4 +/- 5.3 cm; 78.8 +/- 7.6 kg) before and after a CQC simulation in a
      double-blind procedure. Caffeine intake did not improve shooting performance in
      CQC; however, it increased cognitive and somatic anxiety levels. PRACTITIONER
      SUMMARY: According to the previous literature, the ingestion of caffeine could
      help soldiers in operations conducted in sleep deprivation conditions, but in
      stressful combat situations it does not improve the marksmanship of soldiers.

PMID- 25848704
TI  - Molecular mechanism and clinical impact of APOBEC3B-catalyzed mutagenesis in
      breast cancer.
AB  - Cancer genomic DNA sequences enable identification of all mutations and suggest
      targets for precision medicine. The identities and patterns of the mutations
      themselves also provide critical information for deducing the originating DNA
      damaging agents, causal molecular mechanisms, and thus additional therapeutic
      targets. A classic example is ultraviolet light, which crosslinks adjacent
      pyrimidines and leads to C-to-T transitions. A new example is the DNA cytosine
      deaminase APOBEC3B, which was identified recently as a source of DNA damage and
      mutagenesis in breast, head/neck, cervix, bladder, lung, ovary, and to lesser
      extents additional cancer types. This enzyme is normally an effector protein in
      the innate immune response to virus infection but upregulation in these cancer
      types causes elevated levels of genomic C-to-U deamination events, which manifest
      as C-to-T transitions and C-to-G transversions within distinct DNA trinucleotide
      contexts (preferentially 5'-TCA and 5'-TCG). Genomic C-to-U deamination events
      within the same trinucleotide contexts also lead to cytosine mutation clusters
      (kataegis), and may precipitate visible chromosomal aberrations such as
      translocations. Clinical studies indicate that APOBEC3B upregulation correlates
      with poorer outcomes for estrogen receptor-positive breast cancer patients,
      including shorter durations of disease-free survival and overall survival after
      surgery. APOBEC3B may therefore have both diagnostic and prognostic potential.
      APOBEC3B may also be a candidate for therapeutic targeting because inhibition of
      this non-essential enzyme is predicted to decrease tumor mutation rates and
      diminish the likelihood of undesirable mutation-dependent outcomes such as
      recurrence, metastasis, and the development of therapy resistant tumors. 

PMID- 25848707
TI  - Mitochondria fingerprint longevity in iPSCs.

PMID- 25848706
TI  - From pills to patients: an evaluation of data sources to determine the number of
      people living with HIV who are receiving antiretroviral therapy in Germany.
AB  - BACKGROUND: This study aimed to determine the number of people living with HIV
      receiving antiretroviral therapy (ART) between 2006 and 2013 in Germany by using
      the available numbers of antiretroviral drug prescriptions and treatment data
      from the ClinSurv HIV cohort (CSH). METHODS: The CSH is a multi-centre, open,
      long-term observational cohort study with an average number of 10.400 patients in
      the study period 2006-2013. ART has been documented on average for 86% of those
      CSH patients and medication history is well documented in the CSH. RESULTS: The
      proportion of CSH patients receiving TCMs increased continuously over time (from
      85% to 93%; 2006-2013). In contrast, treatment interruptions declined remarkably
      (from 11% to 2%; 2006-2013). The total number of HIV-infected people with ART
      experience in Germany increased from 31,500 (95% CI 31,000-32,000) individuals to
      54,000 (95% CI 53,000-55,500) over the observation period (including 16.3%
      without SHI and persons who had interrupted ART). An average increase of
      approximately 2,900 persons receiving ART was observed annually in Germany.
      CONCLUSIONS: A substantial increase in the number of people receiving ART was
      observed from 2006 to 2013 in Germany.

PMID- 25848705
TI  - Sigma-1 receptor mediates acquisition of alcohol drinking and seeking behavior in
      alcohol-preferring rats.
AB  - Sigma-1 receptor (Sig-1R) has been proposed as a novel therapeutic target for
      drug and alcohol addiction. We have shown previously that Sig-1R agonists
      facilitate the reinforcing effects of ethanol and induce binge-like drinking,
      while Sig-1R antagonists on the other hand block excessive drinking in genetic
      and environmental models of alcoholism, without affecting intake in outbred non
      dependent rats. Even though significant progress has been made in understanding
      the function of Sig-1R in alcohol reinforcement, its role in the early and late
      stage of alcohol addiction remains unclear. Administration of the selective Sig
      1R antagonist BD-1063 dramatically reduced the acquisition of alcohol drinking
      behavior as well as the preference for alcohol in genetically selected TSRI
      Sardinian alcohol preferring (Scr:sP) rats; the treatment had instead no effect
      on total fluid intake, food intake or body weight gain, proving selectivity of
      action. Furthermore, BD-1063 dose-dependently decreased alcohol-seeking behavior
      in rats trained under a second-order schedule of reinforcement, in which
      responding is maintained by contingent presentation of a conditioned reinforcer.
      Finally, an innate elevation in Sig-1R protein levels was found in the nucleus
      accumbens of alcohol-preferring Scr:sP rats, compared to outbred Wistar rats,
      alteration which was normalized by chronic, voluntary alcohol drinking. Taken
      together these findings demonstrate that Sig-1R blockade reduces the propensity
      to both acquire alcohol drinking and to seek alcohol, and point to the nucleus
      accumbens as a potential key region for the effects observed. Our data suggest
      that Sig-1R antagonists may have therapeutic potential in multiple stages of
      alcohol addiction. 

PMID- 25848708
TI  - LNK1 and LNK2 recruitment to the evening element require morning expressed
      circadian related MYB-like transcription factors.
AB  - Transcriptional feedback loops in Arabidopsis circadian clock is composed of more
      repressive components, while the knowledge of activation mechanism remains
      limited. We recently reported 2 members from a family of NIGHT LIGHT-INDUCIBLE
      AND CLOCK-REGULATED genes, LNK1 and LNK2, dynamically interact with morning
      phased transcriptional factors, like CIRCADIAN CLOCK ASSOCIATED1 (CCA1), LATE
      ELONGATED HYPOCOTYL (LHY), REVEILLE8 (RVE8) and RVE4, and function as
      coactivators for the expression of TIMING OF CAB EXPRESSION1 (TOC1) and PSEUDO
      RESPONSE REGULATOR5 (PRR5) via transcriptional factors RVE8 and RVE4. Here we
      provide evidence that both LNK1 and LNK2 play critical role in the
      transcriptional activation of PRR5, LNK1 may contribute more than LNK2 did under
      experimental conditions. We also identified that both LNK1 and LNK2 recruitment
      to the evening element of PRR5 promoter via LNK1-RVE8 or LNK2-RVE8 proteins
      complex through electrophoretic mobility shift assay. Therefore LNK1 and LNK2
      function as coactivator of dawn-phased MYB-like transcription factors, such as
      RVE8 in morning complex to regulate the target genes expression. 

PMID- 25848709
TI  - Janus Suprabead Displays Derived from the Modified Photonic Crystals toward
      Temperature Magnetism and Optics Multiple Responses.
AB  - The design and development of Janus suprabeads (JSs) with multiple responses are
      highly desirable in the fabrication of functional nanomaterials. In this work, we
      report a triphase microfluidic strategy for the construction of JSs with
      temperature-magnetism-optics triple responses. Initially, macromonomer
      poly(methacrylic acid) (PMAA) obtained via catalytic chain transfer
      polymerization (CCTP) was grafted onto the polystyrene (PS) colloidal photonic
      crystals (CPCs) surface. Because abundant carboxylic acid groups in PMAA could
      coordinate cadmium ions for in situ production of fluorescent CdS quantum dots
      (QDs) after introducing sulfur ions, the as-prepared JSs were endowed with
      favorable optical properties. Meanwhile, the as-prepared Cd(2+)/PS CPCs were
      employed as a template to build JSs with temperature-magnetism sensitivity via
      the introduction of magnetic Fe3O4 and hydrogels. Finally, the fluorescence
      pattern was easily performed by using chalcogenides as "ink" to write on the pad,
      in which in situ reaction mechanism was involved in the response. The multiple
      responsive JSs show promising applications in sensor, display, and
      anticounterfeit fields. 

PMID- 25848710
TI  - Pt(II) metal complexes tailored with a newly designed spiro-arranged tetradentate
      ligand; harnessing of charge-transfer phosphorescence and fabrication of sky blue
      and white OLEDs.
AB  - Tetradentate bis(pyridyl azolate) chelates are assembled by connecting two
      bidentate 3-trifluoromethyl-5-(2-pyridyl)azoles at the six position of pyridyl
      fragment with the tailored spiro-arranged fluorene and/or acridine
      functionalities. These new chelates were then utilized in synthesizing a series
      of Pt(II) metal complexes [Pt(Ln)], n = 1-5, from respective chelates L1-L5 and
      [PtCl2(DMSO)2] in 1,2-dimethoxyethane. The single-crystal X-ray structural
      analyses were executed on 1, 3, and 5 to reveal the generalized structures and
      packing arrangement in crystal lattices. Their photophysical properties were
      measured in both solution and solid state and are discussed in the context of
      computational analysis. These L1-L5 coordinated Pt(II) species exhibit intense
      emission, among which complex 5 shows remarkable solvatochromic phosphorescence
      due to the dominant intraligand charge transfer transition induced by the new
      bis(pyridyl azolate) chelates. Moreover, because of the higher-lying highest
      occupied molecular orbital of acridine, complex 5 can be considered as a novel
      bipolar phosphor. Successful fabrication of blue and white organic light-emitting
      diodes (OLEDs) using Pt(II) complexes 3 and 5 as the phosphorescent dopants are
      reported. In particular, blue OLEDs with 5 demonstrated peak efficiencies of
      15.3% (36.3 cd/A, 38.0 lm/W), and CIE values of (0.190, 0.342) in a double
      emitting layer structure. Furthermore, a red-emitting Os(II) complex and 5 were
      used to fabricate warm-white OLEDs to achieve peak external quantum efficiency,
      luminance efficiency, and power efficiency values as high as 12.7%, 22.5 cd/A,
      and 22.1 lm/W, respectively. 

PMID- 25848711
TI  - Laparoscopic Transabdominal With Transdiaphragmatic Access Improves Resection of
      Difficult Posterosuperior Liver Lesions.
AB  - OBJECTIVE: We describe the technical details and evaluate the safety,
      feasibility, and usefulness of a combined lateral and abdominal (CLA) approach
      for laparoscopic resection of liver segments 7 and 8. BACKGROUND: Laparoscopic
      resection of lesions in the posterosuperior area of segments 7 and 8 is
      technically challenging, and currently there is no standardized laparoscopic
      approach. METHODS: Through review of a prospectively maintained database, we
      identified 44 patients who underwent laparoscopic resection of lesions in segment
      7 or 8. Twenty-five patients required the CLA approach because their lesions were
      more posterosuperior and intraparenchymal; 19 patients underwent resection with a
      regular abdominal-only approach of more accessible anteroinferior lesions. We
      reviewed operative details and video footage of these operations and compared the
      outcomes of the 2 groups. RESULTS: In the group treated with the CLA approach,
      deep location was more frequent (88% vs 42%; P = 0.035), median tumor diameter
      was larger (24.5 mm vs 15 mm; P = 0.114), and the median weight of the excised
      parenchyma was greater (56.5 g vs 23 g; P = 0.093). Median operative time was
      longer in the CLA approach group (217.5 minutes vs 165 minutes; P = 0.046), but
      blood loss, rate of conversion to open surgery, surgical margin status,
      morbidity, and mortality were similar between the 2 groups. CONCLUSIONS: The CLA
      approach permits safe laparoscopic resection of lesions in the posterosuperior
      area of segments 7 and 8, allowing surgeons to overcome the difficulties of
      limited visualization and access to the target lesions.

PMID- 25848712
TI  - Moving from strategy to implementation... first steps.

PMID- 25848714
TI  - Evolution of thoracic surgery in Canada.
AB  - BACKGROUND: Canada's contributions toward the 21st century's practice of thoracic
      surgery have been both unique and multilayered. Scattered throughout are tales of
      pioneers where none had gone before, where opportunities were greeted by
      creativity and where iconic figures followed one another. OBJECTIVE: To describe
      the numerous and important achievements of Canadian thoracic surgeons in the
      areas of surgery for pulmonary tuberculosis, thoracic oncology, airway surgery
      and lung transplantation. METHOD: Information was collected through reading of
      the numerous publications written by Canadian thoracic surgeons over the past 100
      years, interviews with interested people from all thoracic surgery divisions
      across Canada and review of pertinent material form the archives of several
      Canadian hospitals and universities. RESULTS: Many of the developments occurred
      by chance. It was the early and specific focus on thoracic surgery, to the
      exclusion of cardiac and general surgery, that distinguishes the Canadian
      experience, a model that is now emerging everywhere. From lung transplantation in
      chimera twin calves to ex vivo organ preservation, from the removal of airways to
      tissue regeneration, and from intensive care research to complex science,
      Canadians have excelled in their commitment to research. Over the years, the
      influence of Canadian thoracic surgery on international practice has been
      significant. CONCLUSIONS: Canada spearheaded the development of thoracic surgery
      over the past 100 years to a greater degree than any other country. From research
      to education, from national infrastructures to the regionalization of local
      practices, it happened in Canada.

PMID- 25848715
TI  - Effective handover communication: Do we need more evidence?

PMID- 25848716
TI  - Partially thrombosed multiple pulmonary artery aneurysm secondary to Behcet
      disease.

PMID- 25848717
TI  - A severe complication of crack cocaine use.
AB  - The present report describes a 48-year-old woman with a history of recurrent
      'crack' cocaine use, who developed progressive shortness of breath over a period
      of years. Serial imaging revealed progressive interstitial fibrosis secondary to
      recurrent alveolar hemorrhage and inflammation from crack cocaine. The present
      case serves as a reminder of the numerous sequelae of crack cocaine use,
      highlighting one particularly severe outcome. 

PMID- 25848719
TI  - E-cigarette use in patients receiving home oxygen therapy.
AB  - Current smokers who are prescribed home oxygen may not benefit from the therapy.
      In addition to being an obvious fire hazard, there is some evidence that the
      physiological mechanisms by which home oxygen is believed to operate are
      inhibited by smoking. Although their effectiveness is yet to be demonstrated,
      electronic cigarettes (e-cigarettes) are often regarded as an aid to smoking
      cessation. However, several burn accidents in e-cigarette smokers receiving home
      oxygen therapy have also been reported, leading Health Canada to release a
      warning of fire risk to oxygen therapy patients from e-cigarettes. It is the
      authors' position that patients receiving oxygen should definitely not use e
      cigarettes. The authors provide suggestions for addressing the delicate issue of
      home oxygen therapy in current cigarette and/or e-cigarette smokers. 

PMID- 25848720
TI  - How long does it take to initiate a child on long-term invasive ventilation?
      Results from a Canadian pediatric home ventilation program.
AB  - OBJECTIVE: To assess the length of stay required to initiate long-term invasive
      ventilation at the authors' institution, which would inform future interventional
      strategies to streamline the in-hospital stay for these families. METHODS: A
      retrospective chart review of children initiated on invasive long-term
      ventilation via tracheostomy at the authors' acute care centre between January
      2005 and December 2013 was performed. RESULTS: Thirty-five children were
      initiated on long-term invasive ventilation via tracheostomy at the acute care
      hospital; 19 (54%) were male. The median age at time of admission was 0.52 years
      (interquartile range [IQR] 0.06 to 9.58 years) . Musculoskeletal disease (n=11
      [31%]) was the most common reason for tracheostomy insertion. Two children died
      during the hospital admission. Fifteen children were discharged home directly
      from the acute care hospital and 18 were moved to the rehabilitation hospital.
      Six are current inpatients of the rehabilitation centre and were never discharged
      home. Combining the length of stay at the acute care and rehabilitation hospitals
      for the entire cohort, the median length of stay was 162.0 days (IQR 98.0 to
      275.0 days) and 97.0 days (IQR 69.0 to 210.0 days), respectively, from the time
      of tracheostomy insertion. CONCLUSIONS: The median length of stay from the
      initiation of invasive long-term ventilation to discharge home from the
      rehabilitation hospital was somewhat long compared with other ventilation
      programs worldwide. Additionally, approximately 20% of the cohort never
      transitioned home. There is a timely need to benchmark across the country and
      internationally, to identify and implement strategies for cohesive, coordinated
      care for these children to decrease overall length of stay.

PMID- 25848721
TI  - Jump-Squat Performance and Its Relationship With Relative Training Intensity in
      High-Level Athletes.
AB  - PURPOSE: To examine the relationship between the relative load in full squats and
      the height achieved in jump-squat (JS) exercises and to determine the load that
      maximizes the power output of high-level athletes. METHOD: Fifty-one male high
      level track-and-field athletes (age 25.2 +/- 4.4 y, weight 77. +/- 6.2 kg, height
      179.9 +/- 5.6 cm) who competed in sprinting and jumping events took part in the
      study. Full-squat 1-repetition-maximum (1-RM) and JS height (JH) with loads from
      17 to 97 kg were measured in 2 sessions separated by 48 h. RESULTS: Individual
      regression analyses showed that JH (R2 = .992 +/- .005) and the jump decrease
      (JD) that each load produced with respect to the unloaded countermovement jump
      (CMJ) (R2 = .992 +/- 0.007) are highly correlated with the full-squat %1-RM,
      which means that training intensities can be prescribed using JH and JD values.
      The authors also found that the load that maximizes JS's power output was 0%RM
      (ie, unloaded CMJ). CONCLUSIONS: These results highlight the close relationship
      between JS performance and relative training intensity in terms of %1-RM. The
      authors also observed that the load that maximizes power output was 0%1-RM.
      Monitoring jump height during JS training could help coaches and athletes
      determine and optimize their training loads.

PMID- 25848722
TI  - Sequential one-pot multienzyme (OPME) synthesis of lacto-N-neotetraose and its
      sialyl and fucosyl derivatives.
AB  - Lacto-N-neotetraose and its sialyl and fucosyl derivatives including Lewis x
      (Le(x)) pentasaccharide, sialyl Lewis x (sLe(x)) hexasaccharide and internally
      sialylated derivatives were enzymatically synthesized from readily available
      lactoside, commercially available uridine 5'-diphosphate-glucose (UDP-Glc) and
      the corresponding monosaccharides using a highly efficient sequential one-pot
      multienzyme (OPME) strategy. The OPME strategy which combines bacterial
      glycosyltransferases and sugar nucleotide generation enzymes provides easy access
      to the biologically important complex oligosaccharides at preparative scale.
      Moreover, the same OPME strategy can be used for the regioselective introduction
      of sialic acid to the internal galactose unit of LNnT in a designed glycosylation
      route by simply changing the glycosylation sequence. 

PMID- 25848723
TI  - Lectin RCA-I specifically binds to metastasis-associated cell surface glycans in
      triple-negative breast cancer.
AB  - INTRODUCTION: Triple-negative breast cancer (TNBC) patients often face a high
      risk of early relapse characterized by extensive metastasis. Previous works have
      shown that aberrant cell surface glycosylation is associated with cancer
      metastasis, suggesting that altered glycosylations might serve as diagnostic
      signatures of metastatic potential. To address this question, we took TNBC as an
      example and analyzed six TNBC cell lines, derived from a common progenitor, that
      differ in metastatic potential. METHODS: We used a microarray with 91 lectins to
      screen for altered lectin bindings to the six TNBC cell lines. Candidate lectins
      were then verified by lectin-based flow cytometry and immunofluorescent staining
      assays using both TNBC/non-TNBC cancer cells. Patient-derived tissue microarrays
      were then employed to analyze whether the staining of Ricinus communis agglutinin
      I (RCA-I), correlated with TNBC severity. We also carried out real-time cell
      motility assays in the presence of RCA-I. Finally, liquid chromatography-mass
      spectrometry/tandem spectrometry (LC-MS/MS) was employed to identify the membrane
      glycoproteins recognized by RCA-I. RESULTS: Using the lectin microarray, we found
      that the bindings of RCA-I to TNBC cells are proportional to their metastatic
      capacity. Tissue microarray experiments showed that the intensity of RCA-I
      staining is positively correlated with the TNM grades. The real-time cell
      motility assays clearly demonstrated RCA-I inhibition of adhesion, migration, and
      invasion of TNBC cells of high metastatic capacity. Additionally, a membrane
      glycoprotein, POTE ankyrin domain family member F (POTEF), with different
      galactosylation extents in high/low metastatic TNBC cells was identified by LC
      MS/MS as a binder of RCA-I. CONCLUSIONS: We discovered RCA-I, which bound to TNBC
      cells to a degree that is proportional to their metastatic capacities, and found
      that this binding inhibits the cell invasion, migration, and adhesion, and
      identified a membrane protein, POTEF, which may play a key role in mediating
      these effects. These results thus indicate that RCA-I-specific cell surface
      glycoproteins may play a critical role in TNBC metastasis and that the extent of
      RCA-I cell binding could be used in diagnosis to predict the likelihood of
      developing metastases in TNBC patients.

PMID- 25848724
TI  - Designing of dynamic polyethyleneimine (PEI) brushes on polyurethane (PU)
      ureteral stents to prevent infections.
AB  - Permanent antibacterial coatings have been developed by brush-like
      polyethyleneimine (PEI) on polyurethane (PU) ureteral stents since bacterial
      adhesion and biofilm formation with the following encrustation on stent surface
      limit their long term usage. In order to control or prevent bacterial infections;
      PEI chains with two different molecular weights (Mn: 1800 or 60,000 Da) were
      covalently attached on the polyurethane (PU) surface by "grafting to" approach to
      obtain a brush-like structure. Then, PEI brushes were alkylated with bromohexane
      to enhance the disruption of bacterial membranes with increasing polycationic
      character. X-ray Photoelectron and Infrared Spectroscopy investigations confirmed
      that PEI grafting and alkylation steps were performed successfully. Surface
      roughness in dry state increased dramatically from 65.8 nm to 277.7 nm and 145.2
      nm for short chain PEI and long chain PEI grafted samples, respectively. Both low
      and high molecular weight PEI grafts exhibited a brush-like structure and potent
      antibacterial activity by lowering the adherence of Klebsiella pneumonia,
      Escherichia coli and Proteus mirabilis species up to two orders of magnitude
      without any cytotoxic effect on L929 and G/G cells. Thus, permanent bactericidal
      activity was achieved by the contact-active strategy of dynamic PEI brush-like
      structures on polyurethane ureteral stent.

PMID- 25848726
TI  - Surface-enhanced Raman scattering (SERS)-active gold nanochains for multiplex
      detection and photodynamic therapy of cancer.
AB  - Multifunctional nanomedicine holds considerable promise as the next generation of
      medicine that will enable early detection of diseases, as well as simultaneous
      monitoring and therapy with minimal toxicity. In particular, surface-enhanced
      Raman scattering (SERS) technology with high sensitivity and multiplexing
      capabilities is emerging as a powerful alternative for identifying specific
      biological targets in live cells. In this paper, we present the synthesis of SERS
      active gold nanochains (AuNCs) as a potential theranostic system for multiplex
      detection and photodynamic therapy (PDT) of cancer. AuNCs were prepared by a
      simple physical mixing method to assemble citrate-stabilized gold nanoparticles
      into nanochains using hyaluronic acid and hydrocaffeic acid (HA-HCA) conjugates
      as templates. In addition, Raman reporters and photosensitizers (PSs) were
      conjugated onto the surface of the AuNCs for multiplex detection and PDT action.
      After mixing with HA-HCA conjugates, citrate-stabilized gold nanoparticles formed
      the AuNC structure, and AuNC length was controlled by the HCA conjugation ratio
      in the HA-HCA conjugates. AuNCs exhibited maximal absorption in the near-infrared
      (NIR) spectral region and effective SERS property. Confocal microscopy, flow
      cytometry, Raman spectroscopy and Bio-TEM measurements were used to determine
      cellular uptake of the Raman reporter, PS and AuNCs in HeLa cells. AuNCs
      conjugated with Raman reporter and PS (HA-HCAn-Au-Pheo-NPT) showed more than 99%
      cellular uptake and exhibited excellent phototoxicity even at low PS
      concentrations compared with free PS after laser irradiation. This SERS-active
      AuNC (HA-HCAn-Au-Pheo-NPT) shows promise for applications in theranostics,
      integrating SERS imaging and PDT.

PMID- 25848725
TI  - Probing carbonate in bone forming minerals on the nanometre scale.
AB  - To devise new strategies to treat bone disease in an ageing society, a more
      detailed characterisation of the process by which bone mineralises is needed. In
      vitro studies have suggested that carbonated mineral might be a precursor for
      deposition of bone apatite. Increased carbonate content in bone may also have
      significant implications in altering the mechanical properties, for example in
      diseased bone. However, information about the chemistry and coordination
      environment of bone mineral, and their spatial distribution within healthy and
      diseased tissues, is lacking. Spatially resolved analytical transmission electron
      microscopy is the only method available to probe this information at the length
      scale of the collagen fibrils in bone. In this study, scanning transmission
      electron microscopy combined with electron energy-loss spectroscopy (STEM-EELS)
      was used to differentiate between calcium-containing biominerals (hydroxyapatite,
      carbonated hydroxyapatite, beta-tricalcium phosphate and calcite). A carbon K
      edge peak at 290 eV is a direct marker of the presence of carbonate. We found
      that the oxygen K-edge structure changed most significantly between minerals
      allowing discrimination between calcium phosphates and calcium carbonates. The
      presence of carbonate in carbonated HA (CHA) was confirmed by the formation of
      peak at 533 eV in the oxygen K-edge. These observations were confirmed by
      simulations using density functional theory. Finally, we show that this method
      can be utilised to map carbonate from the crystallites in bone. We propose that
      our calibration library of EELS spectra could be extended to provide spatially
      resolved information about the coordination environment within bioceramic
      implants to stimulate the development of structural biomaterials.

PMID- 25848727
TI  - Bone response to a novel Ti-Ta-Nb-Zr alloy.
AB  - Commercially pure titanium (cp-Ti) is regarded as the state-of-the-art material
      for bone-anchored dental devices, whereas the mechanically stronger alloy (Ti-6Al
      4V), made of titanium, aluminum (Al) and vanadium (V), is regarded as the
      material of choice for high-load applications. There is a call for the
      development of new alloys, not only to eliminate the potential toxic effect of Al
      and V but also to meet the challenges imposed on dental and maxillofacial
      reconstructive devices, for example. The present work evaluates a novel, dual
      stage, acid-etched, Ti-Ta-Nb-Zr alloy implant, consisting of elements that create
      low toxicity, with the potential to promote osseointegration in vivo. The alloy
      implants (denoted Ti-Ta-Nb-Zr) were evaluated after 7 days and 28 days in a rat
      tibia model, with reference to commercially pure titanium grade 4 (denoted Ti).
      Analyses were performed with respect to removal torque, histomorphometry and gene
      expression. The Ti-Ta-Nb-Zr showed a significant increase in implant stability
      over time in contrast to the Ti. Further, the histological and gene expression
      analyses suggested faster healing around the Ti-Ta-Nb-Zr, as judged by the
      enhanced remodeling, and mineralization, of the early-formed woven bone and the
      multiple positive correlations between genes denoting inflammation, bone
      formation and remodeling. Based on the present experiments, it is concluded that
      the Ti-Ta-Nb-Zr alloy becomes osseointegrated to at least a similar degree to
      that of pure titanium implants. This alloy is therefore emerging as a novel
      implant material for clinical evaluation.

PMID- 25848728
TI  - beta,gamma-Bis-substituted PNA with configurational and conformational switch:
      preferred binding to cDNA/RNA and cell-uptake studies.
AB  - (S,S)- and (R,R)-beta,gamma-Bis-substituted PNAs were synthesized from the C-2
      symmetric vicinal diamine system embedded in 1,4 dihydroxybutane and 1,4
      dimethoxybutane scaffolds. (R,R)-beta,gamma-Bis-methoxymethyl-PNA derived from d
      tartaric acid was found to be in the right configuration and conformation to be
      an excellent mimic of PNA, endowed with superior ability to enter into cells. 

PMID- 25848729
TI  - Engineered water-soluble two-dimensional magnetic nanocomposites: towards highly
      magnetic relaxometric properties.
AB  - Water dispersible two-dimensional magnetic nanocomposites are formed by phase
      transferring hydrophobic manganese-doped ferrite nanoparticles (MFPs) into
      aqueous solvent using a one-step simple approach involving only graphene oxide
      (GO) as the phase transfer agent. The resultant hydrophilic magnetic
      nanocomposites (MFNs) are surprisingly stable in the aqueous phase despite its
      large hydrodynamic size (dhyd). Because of its unique construct that promotes
      water accessibility towards the MFP core, large MFNs loaded with an 18 nm MFP
      core (MFN-18; dhyd = 577.9 nm) exhibits transverse relaxivity (r2) up to ~6.8
      times (r2 = 800.8 mM [Mn + Fe](-1) s(-1)) higher than the typical individually
      coated MFP-18 with amphiphilic brush copolymers (r2 = 117.3 mM [Mn + Fe](-1) s(
      1)). Meanwhile, the overall nanocomposites dhyd can be further reduced by
      employing a smaller pre-sonicated GO sheet phase transfer agent. As a result of
      using small GO sheets with enhanced hydrophilicity, the r2 of small MFN-18*
      nanocomposites (dhyd = 224.9 nm) increases by approximately 37% (r2 = 1097.4 mM
      [Mn + Fe](-1) s(-1)) as compared to larger MFN-18. From a simple comparative
      study among various magnetic nanocomposites involving a MFP-18 core, the high MFN
      18 r2 relaxivity value can be attributed to enhanced water diffusion and exchange
      due to the GO sheet, allowing better interaction between magnetic the MFP core
      and water protons. The proposed method can be readily extended to convert other
      types of hydrophobic nanoparticles into water-dispersible nanocomposites. 

PMID- 25848730
TI  - Disentangling vibronic and solvent broadening effects in the absorption spectra
      of coumarin derivatives for dye sensitized solar cells.
AB  - We simulate from first-principles the absorption spectra of five structure
      related coumarin derivatives utilized in dye sensitized solar cells (DSSCs),
      investigating the vibronic and solvent contributions to the position and width of
      the spectra in ethanol. Ground and excited state potential energy surfaces (PESs)
      are modeled by Density Functional Theory (DFT) and its time-dependent (TD)
      expression for the excited state (TD-DFT). The solute vibronic structure
      associated with the spectrum is calculated by a TD formalism, accounting for both
      Duschinsky and temperature effects, while solvent inhomogeneous broadening is
      evaluated according to Marcus' theory, computing the solvent reorganization
      energy by the state-specific implementation of the polarizable continuum model
      (PCM) within TD-DFT. We adopted both the standard hybrid PBE0 and the range
      separated CAM-B3LYP functionals showing that the latter performs better both
      concerning the vibronic and solvent-induced contributions to the absorption
      lineshape. The different predictions of the two functionals are then rationalized
      in terms of the charge transfer (CT) character of the transitions showing that,
      in this class of compounds, it is strongly dependent on the nuclear structure.
      Such a dependence introduces a bias in the PBE0 PES that has a drastic impact on
      the vibronic spectra. We show that both the intrinsic vibronic structure and the
      solvent broadening play a relevant role in differentiating the absorption width
      of the five dyes. In this sense, our results provide a guide to understand the
      sources of spectral broadening of this family of dyes, a valuable help for a
      rational design of new molecules to improve DSSC devices. 

PMID- 25848731
TI  - Communicating public health messages.

PMID- 25848732
TI  - Reflections on a 38-year career in public health advocacy: 10 pieces of advice to
      early career researchers and advocates.
AB  - There are many important principles and lessons that public health researchers
      and advocates who hope to influence policy and practice need to consider. In this
      paper, I set out what I consider to be 10 of the most fundamental of these.
      Together, these focus on the importance of preserving public confidence in the
      evidence base underscoring public policy; being clear and concrete about the
      policy reforms you support; emphasising the values on which policy is based;
      understanding the structure, conventions and subtextual features of news
      reporting; developing 'killer facts' with 'earworm' potential; appreciating that
      the advocacy process leading to policy change almost always takes a long time;
      and growing a rhinoceros hide to assist in the inevitable attacks you will face. 

PMID- 25848733
TI  - Should we do battle with antivaccination activists?
AB  - Antivaccination activists have existed since variolation was introduced in Europe
      in the 18th century. Today, they continue to attempt to influence the vaccination
      decisions of parents. Commentators have expressed concern about the impact of
      such activists on vaccination rates and disease outbreaks. Some argue that public
      health advocates should engage in adversarial approaches involving public
      attempts to discredit or stop an antivaccination group or individual. This
      article argues that such adversarial advocacy may not be the most effective way
      to support vaccine programs. It argues this on the basis of what is known to
      influence vaccination attitudes and uptake, and the unintended negative
      consequences that can arise from an adversarial approach. These include drawing
      attention to such activists and their arguments, and potentially alienating the
      most important audience - hesitant parents - where the primary goal is to
      establish trust. The exception is when the antivaccination activists' actions may
      cause direct harm, such as encouraging a 'disease party' or illegal activities.
      Generally, however, advocacy should focus on areas where real gains can be made -
      on policies that directly address determinants of low coverage such as lack of
      opportunity to vaccinate and lack of acceptance of vaccination. This includes
      advocacy for accessible and affordable vaccines. In addressing the global problem
      of vaccine hesitancy, public health has a responsibility to better monitor public
      attitudes, support health professionals in communication, and develop and test
      strategies that engage vaccine-hesitant parents and communities. 

PMID- 25848734
TI  - Fetal alcohol spectrum disorders in Australia--the future is prevention.
AB  - Fetal alcohol spectrum disorders (FASD) are increasingly recognised throughout
      Australia as important, but preventable, disorders that result in lifelong
      problems with health and learning, mental health, behaviour and substance misuse.
      The role of this article is to highlight current efforts, which are in their
      infancy, to recognise and prevent FASD in Australia. A federal parliamentary
      inquiry into FASD (2011), development of an Australian Government 'action plan'
      to prevent FASD (2013) and the announcement in June 2014 of government funding to
      progress the plan and appoint a National FASD Technical Network have focused
      attention on the need for FASD prevention in Australia. Other welcome
      developments include the formation of Parliamentarians for the Prevention of FASD
      (2011), revision of guidelines regarding alcohol use in pregnancy by the National
      Health and Medical Research Council (NHMRC; 2009) and provision of targeted
      funding for FASD research by the NHMRC (2013). Initiatives by Indigenous
      communities to restrict access to alcohol and diagnose and prevent FASD have had
      a significant impact in high-risk communities. The National Organisation for FASD
      has an important ongoing advocacy and educational remit. Nongovernment
      organisations such as the Foundation for Alcohol Research and Education have
      contributed to prevention by developing resources to assist health professionals
      to advise women about the harms of alcohol use in pregnancy; encouraging men to
      abstain from alcohol during the pregnancy; drafting a national plan; and
      advocating for pregnancy warning labels on alcohol. Internationally, in 2014, a
      charter on prevention of FASD was published in The Lancet Global Health, and the
      World Health Organization released guidelines for identification and management
      of substance use in pregnancy. Early recognition and support for individuals with
      FASD is crucial to prevent adverse secondary outcomes; however, primary
      prevention of alcohol use in pregnancy, and hence FASD, should be our future
      goal. The causal pathway to drinking in pregnancy is complex and requires a broad
      social ecological approach. Prevention will take time, must involve all
      government sectors and should incorporate primary, secondary and tertiary
      strategies to target both the broader community and populations at high risk of
      alcohol use during pregnancy. 

PMID- 25848735
TI  - Social media campaigns that make a difference: what can public health learn from
      the corporate sector and other social change marketers?
AB  - AIM: A great deal of enthusiasm and interest exists in using social media for
      public health communications, but few research studies have examined its success
      in promoting and adopting protective health behaviours. To begin to understand
      how best to develop effective online social marketing campaigns, this paper
      provides a summary of success factors and key lessons learnt from selected social
      media campaign case studies. STUDY TYPE: Case study review Methods: A selection
      of case studies was reviewed for lessons in campaign development, delivery and
      evaluation from both the corporate and public health sectors. Information about
      the objective of the campaign, the tactics used and the lessons learnt was
      extracted from each case study. Lessons learnt from across the case studies were
      then sorted according to themes. RESULTS: Lessons from the nine case studies
      selected were categorised into eight themes: planning, use of social media tools,
      community, content, personal benefits, promotion, costs and challenges. Outcome
      evaluation data were lacking in the case studies. CONCLUSIONS: Overall, the nine
      case studies show that social media hold promise in changing user behaviours and
      that social media are highly effective in recruiting participants and motivating
      them to take small, concrete actions. The case studies also demonstrate that
      there is room in social media for targeted, inexpensive, small-scale projects, as
      well as large, well-funded, mass-reach marketing blitzes. Social media campaign
      process and impact evaluation measures are readily available. Outcome evaluation
      models and measures are needed to better assess the effectiveness of social media
      campaigns in changing health behaviours.

PMID- 25848736
TI  - Manual versus automated coding of free-text self-reported medication data in the
      45 and Up Study: a validation study.
AB  - BACKGROUND: Increasingly, automated methods are being used to code free-text
      medication data, but evidence on the validity of these methods is limited. AIM:
      To examine the accuracy of automated coding of previously keyed in free-text
      medication data compared with manual coding of original handwritten free-text
      responses (the 'gold standard'). METHODS: A random sample of 500 participants
      (475 with and 25 without medication data in the free-text box) enrolled in the 45
      and Up Study was selected. Manual coding involved medication experts keying in
      free-text responses and coding using Anatomical Therapeutic Chemical (ATC) codes
      (i.e. chemical substance 7-digit level; chemical subgroup 5-digit;
      pharmacological subgroup 4-digit; therapeutic subgroup 3-digit). Using keyed-in
      free-text responses entered by non-experts, the automated approach coded entries
      using the Australian Medicines Terminology database and assigned corresponding
      ATC codes. RESULTS: Based on manual coding, 1377 free-text entries were recorded
      and, of these, 1282 medications were coded to ATCs manually. The sensitivity of
      automated coding compared with manual coding was 79% (n = 1014) for entries coded
      at the exact ATC level, and 81.6% (n = 1046), 83.0% (n = 1064) and 83.8% (n =
      1074) at the 5, 4 and 3-digit ATC levels, respectively. The sensitivity of
      automated coding for blank responses was 100% compared with manual coding.
      Sensitivity of automated coding was highest for prescription medications and
      lowest for vitamins and supplements, compared with the manual approach. Positive
      predictive values for automated coding were above 95% for 34 of the 38 individual
      prescription medications examined. CONCLUSIONS: Automated coding for free-text
      prescription medication data shows very high to excellent sensitivity and
      positive predictive values, indicating that automated methods can potentially be
      useful for large-scale, medication-related research.

PMID- 25848737
TI  - Reliability study of clinical electronic records with paper records in the NSW
      Public Oral Health Service.
AB  - AIM: Electronic health record (EHR) data have great potential for reuse in
      research and patient care quality improvement initiatives. However, in dual
      systems, where both electronic and paper health records are used, inconsistencies
      and errors may occur. The objective of this study was to determine the degree of
      agreement between EHR clinical data and paper records for reuse in clinical oral
      health research and quality improvement initiatives. METHODS: A random sample of
      200 EHRs for adolescents from eight Area Health Services was obtained from the
      Information System for Oral Health New South Wales database of 29 599 records,
      and compared with 200 paper records for adolescents that were stored at clinics.
      The records were analysed for data reliability. The electronic records were
      percentage weighted to reflect the number of adolescents treated in each of the
      Area Health Services. RESULTS: The results showed an overall 95.0% agreement
      between the 200 individual EHRs and the 200 clinic-stored paper records. In 1.5%
      of cases, information contained in the paper record was not uploaded into the
      EHR, and in 3.5% of cases, information contained in the EHR was missing from the
      paper record. CONCLUSIONS: It is possible to conclude that more deficiencies
      occurred in paper records compared with EHRs. These deficiencies should be taken
      into account if EHRs are to be reused for clinical oral health research or
      quality improvement initiatives. Considering the missing data and the great
      strides in information system technology, it would be logical to adopt one
      system, with a focus on electronic records to replace the paper records.

PMID- 25848738
TI  - Hepatitis C enhanced surveillance: results from a southeastern Sydney pilot
      program.
AB  - AIM: Hepatitis C virus (HCV) is a potentially serious bloodborne virus, which
      persists in the majority of those infected. Long-term sequelae include liver
      cirrhosis, liver cancer and premature death. Early identification of newly
      acquired infection is important for protection of public health. Routine
      surveillance based on laboratory notification of HCV infection is not sufficient
      to differentiate between newly acquired and chronic infections. Enhanced
      surveillance systems have been trialled globally in a number of settings. This
      pilot program aimed to increase identification of newly acquired HCV cases in
      southeastern Sydney residents and to ascertain the likely mode of transmission.
      METHODS: All HCV notifications in southeastern Sydney residents with specimen
      dates from 1 July to 31 December 2012 were included in a pilot program.
      Demographic data, Australian Indigenous identification and previous laboratory
      results were collected from electronic medical records, where available. Enhanced
      surveillance forms were sent to referring doctors to seek information about
      clinical symptoms and previous hepatitis C pathology. Data were collated to
      assess, according to Australian national case definitions, whether cases were
      newly acquired or not, or were unable to be determined on the available
      information. RESULTS: There were 104 notifications of HCV infection during the
      surveillance period. Forms were sent to 100 requesting doctors, with 72 forms
      returned. Six newly acquired cases were identified, a rate of 8%, compared with 1
      3% classified by routine surveillance. Twenty cases (28%) were not newly acquired
      and the status of 46 (64%) was unable to be determined. Of the six newly acquired
      cases, sexual transmission was deemed to be the likely route of exposure for four
      cases, and injecting drug use for the remaining two. CONCLUSIONS: Enhanced
      surveillance increased the rate of identification of newly acquired infections.
      However, the process was labour-intensive and the status of most cases was unable
      to be determined. Since identification of newly acquired cases has an important
      public health benefit in understanding factors in disease transmission, other
      approaches should be examined.

PMID- 25848739
TI  - Piloting proactive marketing to recruit disadvantaged adults to a community-wide
      obesity prevention program.
AB  - Population-wide obesity prevention and treatment programs are fundamental to
      addressing the increasing overweight and obesity rates in socioeconomically
      disadvantaged populations. Innovative recruitment strategies, including proactive
      marketing strategies, are needed to ensure such programs have universal reach and
      target vulnerable populations. This study aimed to determine the success of
      proactive recruitment to Australia's Get Healthy Information and Coaching
      Service(r) (GHS) and to assess whether the recruitment strategy influenced
      participants' outcomes. Sociodemographic information was collected from all GHS
      participants who joined the service between February 2009 and August 2013, and
      anthropometric information regarding behavioural risk factors was collected from
      all GHS coaching participants at baseline and six months. Data were analysed
      according to the participants' referral source (self-referral and secondary
      referral versus proactive recruitment). Participants recruited through proactive
      marketing were more likely to be male, aged 50 years or older, have high school
      education, not be in paid employment and be from the lowest three quintiles of
      socioeconomic advantage. The risk factor profile of coaching participants
      recruited through proactive marketing did not vary significantly from those
      recruited via other mechanisms, although they were less likely to be obese and
      less likely to have a higher 'at risk' waist circumference measurement.
      Proactively recruited coaching participants reported significant improvements
      from baseline to six months (consistent with improvements made by participants
      recruited through other strategies), although they were significantly more likely
      to withdraw from coaching before they completed the six-month program.Proactive
      marketing facilitated use of an obesity prevention service; similar services may
      have greater reach if proactive marketing recruitment strategies are used. These
      strategies could be encouraged to assist such services to achieve optimal
      population impact among hard-to-reach populations. 

PMID- 25848740
TI  - Health promotion 'on steroids': the value of an experiential approach to promote
      rapid HIV testing in NSW, Australia.
AB  - In 2012, there was a sharp increase in human immunodeficiency virus (HIV)
      notifications in New South Wales (NSW), Australia, following a 10-year period of
      relative stability. This increase, among other factors, triggered the development
      of a new HIV strategy that included renewed efforts to increase testing to
      improve early diagnosis, enable early treatment and reduce the risk of onward
      transmission. This article describes the activities conducted by NSW Health and
      partner organisations during November 2013 in the week before World AIDS Day
      (phase one (P1)) and HIV testing week in July 2014 (phase 2 (P2)). A model of pop
      up HIV testing, new to Australia, was used to take testing to those most at risk
      of infection, and was promoted through social media and experiential techniques.
      During P1, an average of seven tests per hour were conducted at the pop-up
      service, compared with four tests per hour at a fast-track screening service in a
      nearby sexual health clinic. During HIV testing week, the campaign hashtag was
      mentioned an average of 56 times per day, following a baseline of six mentions
      per day one week before. The estimated total social media reach was 549,769
      people via 459 posts. The pop-up testing model proved popular, and the use of
      social media and experiential techniques has extended the reach of the 'test
      more' messages. Further research is required to determine causality between
      specific HIV messaging and experiential techniques and testing rates.

PMID- 25848741
TI  - Plain packaging an "extraordinary success".

PMID- 25848742
TI  - NSW pledges support for FASD.

PMID- 25848743
TI  - 'No jab, no pay' recommendation raises concerns.

PMID- 25848744
TI  - The asymmetry of female meiosis reduces the frequency of inheritance of unpaired
      chromosomes.
AB  - Trisomy, the presence of a third copy of one chromosome, is deleterious and
      results in inviable or defective progeny if passed through the germ line. Random
      segregation of an extra chromosome is predicted to result in a high frequency of
      trisomic offspring from a trisomic parent. Caenorhabditis elegans with trisomy of
      the X chromosome, however, have far fewer trisomic offspring than expected. We
      found that the extra X chromosome was preferentially eliminated during anaphase I
      of female meiosis. We utilized a mutant with a specific defect in pairing of the
      X chromosome as a model to investigate the apparent bias against univalent
      inheritance. First, univalents lagged during anaphase I and their movement was
      biased toward the cortex and future polar body. Second, late-lagging univalents
      were frequently captured by the ingressing polar body contractile ring. The
      asymmetry of female meiosis can thus partially correct pre-existing trisomy. 

PMID- 25848745
TI  - In vivo targeting of de novo DNA methylation by histone modifications in yeast
      and mouse.
AB  - Methylation of cytosines (5(me)C) is a widespread heritable DNA modification.
      During mammalian development, two global demethylation events are followed by
      waves of de novo DNA methylation. In vivo mechanisms of DNA methylation
      establishment are largely uncharacterized. Here, we use Saccharomyces cerevisiae
      as a system lacking DNA methylation to define the chromatin features influencing
      the activity of the murine DNMT3B. Our data demonstrate that DNMT3B and H3K4
      methylation are mutually exclusive and that DNMT3B is co-localized with H3K36
      methylated regions. In support of this observation, DNA methylation analysis in
      yeast strains without Set1 and Set2 shows an increase of relative 5(me)C levels
      at the transcription start site and a decrease in the gene-body, respectively. We
      extend our observation to the murine male germline, where H3K4me3 is strongly
      anti-correlated while H3K36me3 correlates with accelerated DNA methylation. These
      results show the importance of H3K36 methylation for gene-body DNA methylation in
      vivo. 

PMID- 25848746
TI  - ERBB2 triggers mammalian heart regeneration by promoting cardiomyocyte
      dedifferentiation and proliferation.
AB  - The murine neonatal heart can regenerate after injury through cardiomyocyte (CM)
      proliferation, although this capacity markedly diminishes after the first week of
      life. Neuregulin-1 (NRG1) administration has been proposed as a strategy to
      promote cardiac regeneration. Here, using loss- and gain-of-function genetic
      tools, we explore the role of the NRG1 co-receptor ERBB2 in cardiac regeneration.
      NRG1-induced CM proliferation diminished one week after birth owing to a
      reduction in ERBB2 expression. CM-specific Erbb2 knockout revealed that ERBB2 is
      required for CM proliferation at embryonic/neonatal stages. Induction of a
      constitutively active ERBB2 (caERBB2) in neonatal, juvenile and adult CMs
      resulted in cardiomegaly, characterized by extensive CM hypertrophy,
      dedifferentiation and proliferation, differentially mediated by ERK, AKT and
      GSK3beta/beta-catenin signalling pathways. Transient induction of caERBB2
      following myocardial infarction triggered CM dedifferentiation and proliferation
      followed by redifferentiation and regeneration. Thus, ERBB2 is both necessary for
      CM proliferation and sufficient to reactivate postnatal CM proliferative and
      regenerative potentials. 

PMID- 25848747
TI  - Independent and coordinate trafficking of single Drosophila germ plasm mRNAs.
AB  - Messenger RNA localization is a conserved mechanism for spatial control of
      protein synthesis, with key roles in generating cellular and developmental
      asymmetry. Whereas different transcripts may be targeted to the same subcellular
      domain, the extent to which their localization is coordinated is unclear. Using
      quantitative single-molecule imaging, we analysed the assembly of Drosophila germ
      plasm mRNA granules inherited by nascent germ cells. We find that the germ-cell
      destined transcripts nanos, cyclin B and polar granule component travel within
      the oocyte as ribonucleoprotein particles containing single mRNA molecules but co
      assemble into multi-copy heterogeneous granules selectively at the posterior of
      the oocyte. The stoichiometry and dynamics of assembly indicate a defined
      stepwise sequence. Our data suggest that co-packaging of these transcripts
      ensures their effective segregation to germ cells. In contrast,
      compartmentalization of the germline determinant oskar mRNA into different
      granules limits its entry into germ cells. This exclusion is required for proper
      germline development. 

PMID- 25848748
TI  - Exome sequencing links mutations in PARN and RTEL1 with familial pulmonary
      fibrosis and telomere shortening.
AB  - Idiopathic pulmonary fibrosis (IPF) is an age-related disease featuring
      progressive lung scarring. To elucidate the molecular basis of IPF, we performed
      exome sequencing of familial kindreds with pulmonary fibrosis. Gene burden
      analysis comparing 78 European cases and 2,816 controls implicated PARN, an
      exoribonuclease with no previous connection to telomere biology or disease, with
      five new heterozygous damaging mutations in unrelated cases and none in controls
      (P = 1.3 * 10(-8)); mutations were shared by all affected relatives (odds in
      favor of linkage = 4,096:1). RTEL1, an established locus for dyskeratosis
      congenita, harbored significantly more new damaging and missense variants at
      conserved residues in cases than in controls (P = 1.6 * 10(-6)). PARN and RTEL1
      mutation carriers had shortened leukocyte telomere lengths, and we observed
      epigenetic inheritance of short telomeres in family members. Together, these
      genes explain ~7% of familial pulmonary fibrosis and strengthen the link between
      lung fibrosis and telomere dysfunction.

PMID- 25848749
TI  - Exploring population size changes using SNP frequency spectra.
AB  - Inferring demographic history is an important task in population genetics. Many
      existing inference methods are based on predefined simplified population models,
      which are more suitable for hypothesis testing than exploratory analysis. We
      developed a novel model-flexible method called stairway plot, which infers
      changes in population size over time using SNP frequency spectra. This method is
      applicable for whole-genome sequences of hundreds of individuals. Using extensive
      simulation, we demonstrate the usefulness of the method for inferring demographic
      history, especially recent changes in population size. We apply the method to the
      whole-genome sequence data of 9 populations from the 1000 Genomes Project and
      show a pattern of fluctuations in human populations from 10,000 to 200,000 years
      ago.

PMID- 25848751
TI  - Mutational landscape and clonal architecture in grade II and III gliomas.
AB  - Grade II and III gliomas are generally slowly progressing brain cancers, many of
      which eventually transform into more aggressive tumors. Despite recent findings
      of frequent mutations in IDH1 and other genes, knowledge about their pathogenesis
      is still incomplete. Here, combining two large sets of high-throughput sequencing
      data, we delineate the entire picture of genetic alterations and affected
      pathways in these glioma types, with sensitive detection of driver genes. Grade
      II and III gliomas comprise three distinct subtypes characterized by discrete
      sets of mutations and distinct clinical behaviors. Mutations showed significant
      positive and negative correlations and a chronological hierarchy, as inferred
      from different allelic burdens among coexisting mutations, suggesting that there
      is functional interplay between the mutations that drive clonal selection.
      Extensive serial and multi-regional sampling analyses further supported this
      finding and also identified a high degree of temporal and spatial heterogeneity
      generated during tumor expansion and relapse, which is likely shaped by the
      complex but ordered processes of multiple clonal selection and evolutionary
      events. 

PMID- 25848750
TI  - Transposon mutagenesis identifies genetic drivers of Braf(V600E) melanoma.
AB  - Although nearly half of human melanomas harbor oncogenic BRAF(V600E) mutations,
      the genetic events that cooperate with these mutations to drive melanogenesis are
      still largely unknown. Here we show that Sleeping Beauty (SB) transposon-mediated
      mutagenesis drives melanoma progression in Braf(V600E) mutant mice and identify
      1,232 recurrently mutated candidate cancer genes (CCGs) from 70 SB-driven
      melanomas. CCGs are enriched in Wnt, PI3K, MAPK and netrin signaling pathway
      components and are more highly connected to one another than predicted by chance,
      indicating that SB targets cooperative genetic networks in melanoma. Human
      orthologs of >500 CCGs are enriched for mutations in human melanoma or showed
      statistically significant clinical associations between RNA abundance and
      survival of patients with metastatic melanoma. We also functionally validate
      CEP350 as a new tumor-suppressor gene in human melanoma. SB mutagenesis has thus
      helped to catalog the cooperative molecular mechanisms driving BRAF(V600E)
      melanoma and discover new genes with potential clinical importance in human
      melanoma.

PMID- 25848752
TI  - Genetic conflict reflected in tissue-specific maps of genomic imprinting in human
      and mouse.
AB  - Genomic imprinting is an epigenetic process that restricts gene expression to
      either the maternally or paternally inherited allele. Many theories have been
      proposed to explain its evolutionary origin, but understanding has been limited
      by a paucity of data mapping the breadth and dynamics of imprinting within any
      organism. We generated an atlas of imprinting spanning 33 mouse and 45 human
      developmental stages and tissues. Nearly all imprinted genes were imprinted in
      early development and either retained their parent-of-origin expression in adults
      or lost it completely. Consistent with an evolutionary signature of parental
      conflict, imprinted genes were enriched for coexpressed pairs of maternally and
      paternally expressed genes, showed accelerated expression divergence between
      human and mouse, and were more highly expressed than their non-imprinted
      orthologs in other species. Our approach demonstrates a general framework for the
      discovery of imprinting in any species and sheds light on the causes and
      consequences of genomic imprinting in mammals.

PMID- 25848753
TI  - Biallelic mutations in SNX14 cause a syndromic form of cerebellar atrophy and
      lysosome-autophagosome dysfunction.
AB  - Pediatric-onset ataxias often present clinically as developmental delay and
      intellectual disability, with prominent cerebellar atrophy as a key
      neuroradiographic finding. Here we describe a new clinically distinguishable
      recessive syndrome in 12 families with cerebellar atrophy together with ataxia,
      coarsened facial features and intellectual disability, due to truncating
      mutations in the sorting nexin gene SNX14, encoding a ubiquitously expressed
      modular PX domain-containing sorting factor. We found SNX14 localized to
      lysosomes and associated with phosphatidylinositol (3,5)-bisphosphate, a key
      component of late endosomes/lysosomes. Patient-derived cells showed engorged
      lysosomes and a slower autophagosome clearance rate upon autophagy induction by
      starvation. Zebrafish morphants for snx14 showed dramatic loss of cerebellar
      parenchyma, accumulation of autophagosomes and activation of apoptosis. Our
      results characterize a unique ataxia syndrome due to biallelic SNX14 mutations
      leading to lysosome-autophagosome dysfunction. 

PMID- 25848754
TI  - FBXL10 protects Polycomb-bound genes from hypermethylation.
AB  - Nearly all CpG-dense promoters are occupied by the multidomain chromosomal
      protein FBXL10. We show here that complete inactivation of the Fbxl10 gene leads
      to dense de novo methylation only of promoters that are co-occupied by both
      FBXL10 and Polycomb repressive complexes; this methylation results in pervasive
      defects in embryonic development and the death of homozygous Fbxl10-mutant
      embryos at midgestation. Deletion of key components of Polycomb repressive
      complexes 1 and 2 did not lead to ectopic genomic methylation. These results
      indicate that FBXL10 protects Polycomb-occupied promoters against ectopic de novo
      methylation. To our knowledge, FBXL10 is the first reported factor whose loss
      leads to a gain in genomic DNA methylation. 

PMID- 25848756
TI  - Regulatory T cells: Young AIREs go on to rule.

PMID- 25848757
TI  - Coverage-dependent thermodynamic analysis of the formation of water and hydrogen
      peroxide on a platinum model catalyst.
AB  - Understanding the selectivity of the oxygen reduction reaction, especially the
      formation of water versus hydrogen peroxide in fuel cells, is an ongoing
      challenge in electrochemistry, surface science and catalysis. In this study, we
      propose a comprehensive thermodynamic analysis of the reaction intermediates for
      the formation of water on Pt(111). Density functional theory calculations of all
      the elementary steps linking hydroxyl and hydroperoxyl surface species with water
      and hydrogen peroxide have been performed at low (1/12 ML, ML = monolayer) and
      high (1/4 ML) coverages. The reaction energy variation for the two competing
      elementary events (molecular oxygen dissociation and hydroperoxyl formation) is
      strongly coverage-dependent. For the direct dissociation, an increase is observed
      at low coverage with respect to the usual high coverage picture. The stability of
      the reaction intermediates is investigated from thermodynamic diagrams. At 353 K
      and a total pressure of 1 atm, water and hydroxyl surface species are expected to
      compete for adsorption on Pt(111). 

PMID- 25848755
TI  - The development and in vivo function of T helper 9 cells.
AB  - The specialized cytokine secretion profiles of T helper (TH) cells are the basis
      for a focused and efficient immune response. On the twentieth anniversary of the
      first descriptions of the cytokine signals that promote the differentiation of
      interleukin-9 (IL-9)-secreting T cells, this Review focuses on the extracellular
      signals and the transcription factors that promote the development of what we now
      term TH9 cells, which are characterized by the production of this cytokine. We
      summarize our current understanding of the contribution of TH9 cells to both
      effective immunity and immunopathological disease, and we propose that TH9 cells
      could be targeted for the treatment of allergic and autoimmune disease. 

PMID- 25848758
TI  - Aberrant beliefs and reasoning.

PMID- 25848759
TI  - Effects of Tithonia diversifolia (Hemsl.) A. Gray extract on adipocyte
      differentiation of human mesenchymal stem cells.
AB  - Tithonia diversifolia (Hemsl.) A. Gray (Asteraceae) is widely used in traditional
      medicine. There is increasing interest on the in vivo protective effects of
      natural compounds contained in plants against oxidative damage caused from
      reactive oxygen species. In the present study the total phenolic and flavonoid
      contents of aqueous, methanol and dichloromethane extracts of leaves of Tithonia
      diversifolia (Hemsl.) A. Gray were determined; furthermore, free radical
      scavenging capacity of each extract and the ability of these extracts to inhibit
      in vitro plasma lipid peroxidation were also evaluated. Since oxidative stress
      may be involved in trasformation of pre-adipocytes into adipocytes, to test the
      hypothesis that Tithonia extract may also affect adipocyte differentiation, human
      mesenchymal stem cell cultures were treated with Tithonia diversifolia aqueous
      extract and cell viability, free radical levels, Oil-Red O staining and western
      bolt analysis for heme oxygenase and 5'-adenosine monophoshate-activated protein
      kinase were carried out. Results obtained in the present study provide evidence
      that Tithonia diversifolia (Hemsl.) A. Gray exhibits interesting health promoting
      properties, resulting both from its free radical scavenger capacity and also by
      induction of protective cellular systems involved in cellular stress defenses and
      in adipogenesis of mesenchymal cells. 

PMID- 25848760
TI  - A common variant of ubiquinol-cytochrome c reductase complex is associated with
      DDH.
AB  - PURPOSE: Genetic basis of Developmental dysplasia of the hip (DDH) remains
      largely unknown. To find new susceptibility genes for DDH, we carried out a
      genome-wide association study (GWAS) for DDH. METHODS: We enrolled 386 radiology
      confirmed DDH patients and 558 healthy controls (Set A) to conduct a genome-wide
      association study (GWAS). Quality-control was conducted at both the sample and
      single nucleotide polymorphism (SNP) levels. We then conducted a subsequent case
      control study to replicate the association between a promising loci, rs6060373 in
      UQCC gene and DDH in an independent set of 755 cases and 944 controls (set B).
      RESULTS: In the DDH GWAS discovering stage, 51 SNPs showed significance of less
      than 10-4, and another 577 SNPs showed significance of less than 10-3. In UQCC,
      all the 12 genotyped SNPs showed as promising risk loci. Genotyping of rs6060373
      in set A showed the minor allele A as a promising risk allele (p = 4.82*10-7). In
      set A, the odds ratio of allele A was 1.77. Genotyping of rs6060373 in Set B
      produced another significant result (p = 0.0338) with an odds ratio of 1.18 for
      risk allele A. Combining set A and set B, we identified a total p value of
      3.63*10-6 with the odds ratio of 1.35 (1.19-1.53) for allele A. CONCLUSION: Our
      study demonstrates common variants of UQCC, specifically rs6060373, are
      associated with DDH in Han Chinese population.

PMID- 25848761
TI  - Postnatal depression among rural women in South India: do socio-demographic,
      obstetric and pregnancy outcome have a role to play?
AB  - INTRODUCTION: Postnatal depression (PND) is one of the most common
      psychopathology and is considered as a serious public health issue because of its
      devastating effects on mother, family, and infant or the child. OBJECTIVE: To
      elicit socio-demographic, obstetric and pregnancy outcome predictors of Postnatal
      Depression (PND) among rural postnatal women in Karnataka state, India. DESIGN:
      Hospital based analytical cross sectional study. SETTING: A rural tertiary care
      hospital of Mandya District, Karnataka state, India. SAMPLE: PND prevalence based
      estimated sample of 102 women who came for postnatal follow up from 4th to 10th
      week of lactation. METHOD: Study participants were interviewed using validated
      kannada version of Edinburgh Postnatal Depression Scale (EPDS). Cut-off score of
      >= 13 was used as high risk of PND. The percentage of women at risk of PND was
      estimated, and differences according to socio-demographic, obstetric and
      pregnancy outcome were described. Logistic regression was applied to identify the
      independent predictors of PND risk. MAIN OUTCOME MEASURES: Prevalence, Odds ratio
      (OR) and adjusted (adj) OR of PND. RESULTS: Prevalence of PND was 31.4% (95% CI
      22.7-41.4%). PND showed significant (P < 0.05) association with joint family,
      working women, non-farmer husbands, poverty, female baby and pregnancy
      complications or known medical illness. In binomial logistic regression poverty
      (adjOR: 11.95, 95% CI:1.36-105), birth of female baby (adjOR: 3.6, 95% CI:1.26
      10.23) and pregnancy complications or known medical illness (adjOR: 17.4, 95%
      CI:2.5-121.2) remained as independent predictors of PND. CONCLUSION: Risk of PND
      among rural postnatal women was high (31.4%). Birth of female baby, poverty and
      complications in pregnancy or known medical illness could predict the high risk
      of PND. PND screening should be an integral part of postnatal care. Capacity
      building of grass root level workers and feasibility trials for screening PND by
      them are needed.

PMID- 25848763
TI  - Multi-lineage differentiation of human umbilical cord Wharton's Jelly Mesenchymal
      Stromal Cells mediates changes in the expression profile of stemness markers.
AB  - Wharton's Jelly- derived Mesenchymal stem cells (WJ-MSCs) have gained interest as
      an alternative source of stem cells for regenerative medicine because of their
      potential for self-renewal, differentiation and unique immunomodulatory
      properties. Although many studies have characterized various WJ-MSCs
      biologically, the expression profiles of the commonly used stemness markers have
      not yet been addressed. In this study, WJ-MSCs were isolated and characterized
      for stemness and surface markers expression. Flow cytometry, immunofluorescence
      and qRT-PCR analysis revealed predominant expression of CD29, CD44, CD73, CD90,
      CD105 and CD166 in WJ-MSCs, while the hematopoietic and endothelial markers were
      absent. Differential expression of CD 29, CD90, CD105 and CD166 following
      adipogenic, osteogenic and chondrogenic induction was observed. Furthermore, our
      results demonstrated a reduction in CD44 and CD73 expressions in response to the
      tri-lineage differentiation induction, suggesting that they can be used as
      reliable stemness markers, since their expression was associated with
      undifferentiated WJ-MSCs only. 

PMID- 25848762
TI  - The determinants of traditional medicine use in Northern Tanzania: a mixed
      methods study.
AB  - INTRODUCTION: Traditional medicines are an important part of healthcare in sub
      Saharan Africa, and building successful disease treatment programs that are
      sensitive to traditional medicine practices will require an understanding of
      their current use and roles, including from a biomedical perspective. Therefore,
      we conducted a mixed-method study in Northern Tanzania in order to characterize
      the extent of and reasons for the use of traditional medicines among the general
      population so that we can better inform public health efforts in the region.
      METHODS: Between December 2013 and June 2014 in Kilimanjaro, Tanzania, we
      conducted 5 focus group discussions and 27 in-depth interviews of key informants.
      The data from these sessions were analyzed using an inductive framework method
      with cultural insider-outsider coding. From these results, we developed a
      structured survey designed to test different aspects of traditional medicine use
      and administered it to a random sample of 655 adults from the community. The
      results were triangulated to explore converging and diverging themes. RESULTS:
      Most structured survey participants (68%) reported knowing someone who frequently
      used traditional medicines, and the majority (56%) reported using them themselves
      in the previous year. The most common uses were for symptomatic ailments (42%),
      chronic diseases (15%), reproductive problems (11%), and malaria/febrile
      illnesses (11%). We identified five major determinants for traditional medicine
      use in Northern Tanzania: biomedical healthcare delivery, credibility of
      traditional practices, strong cultural identities, individual health status, and
      disease understanding. CONCLUSIONS: In order to better formulate effective local
      disease management programs that are sensitive to TM practices, we described the
      determinants of TM use. Additionally, we found TM use to be high in Northern
      Tanzania and that its use is not limited to lower-income areas or rural settings.
      After symptomatic ailments, chronic diseases were reported as the most common
      reason for TM use which may be particularly important in Northern Tanzania where
      non-communicable diseases are a rapidly growing burden.

PMID- 25848764
TI  - Myocardial feature tracking reduces observer-dependence in low-dose dobutamine
      stress cardiovascular magnetic resonance.
AB  - OBJECTIVES: To determine whether quantitative wall motion assessment by CMR
      myocardial feature tracking (CMR-FT) would reduce the impact of observer
      experience as compared to visual analysis in patients with ischemic
      cardiomyopathy (ICM). METHODS: 15 consecutive patients with ICM referred for
      assessment of hibernating myocardium were studied at 3 Tesla using SSFP cine
      images at rest and during low dose dobutamine stress (5 and 10 MUg/kg/min of
      dobutamine). Conventional visual, qualitative analysis was performed
      independently and blinded by an experienced and an inexperienced reader, followed
      by post-processing of the same images by CMR-FT to quantify subendocardial and
      subepicardial circumferential (Eccendo and Eccepi) and radial (Err) strain.
      Receiver operator characteristics (ROC) were assessed for each strain parameter
      and operator to detect the presence of inotropic reserve as visually defined by
      the experienced observer. RESULTS: 141 segments with wall motion abnormalities at
      rest were eligible for the analysis. Visual scoring of wall motion at rest and
      during dobutamine was significantly different between the experienced and the
      inexperienced observer (p<0.001). All strain values (Eccendo, Eccepi and Err)
      derived during dobutamine stress (5 and 10 MUg/kg/min) showed similar diagnostic
      accuracy for the detection of contractile reserve for both operators with no
      differences in ROC (p>0.05). Eccendo was the most accurate (AUC of 0.76, 10
      MUg/kg/min of dobutamine) parameter. Diagnostic accuracy was worse for resting
      strain with differences between operators for Eccendo and Eccepi (p<0.05) but not
      Err (p>0.05). CONCLUSION: Whilst visual analysis remains highly dependent on
      operator experience, quantitative CMR-FT analysis of myocardial wall mechanics
      during DS-CMR provides diagnostic accuracy for the detection of inotropic reserve
      regardless of operator experience and hence may improve diagnostic robustness of
      low-dose DS-CMR in clinical practice.

PMID- 25848765
TI  - High expression of KCa3.1 in patients with clear cell renal carcinoma predicts
      high metastatic risk and poor survival.
AB  - BACKGROUND: Ca2+-activated K+ channels have been implicated in cancer cell
      growth, metastasis, and tumor angiogenesis. Here we hypothesized that high mRNA
      and protein expression of the intermediate-conductance Ca2+-activated K+ channel,
      KCa3.1, is a molecular marker of clear cell Renal Cell Carcinoma (ccRCC) and
      metastatic potential and survival. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed
      channel expression by qRT-PCR, immunohistochemistry, and patch-clamp in ccRCC and
      benign oncocytoma specimens, in primary ccRCC and oncocytoma cell lines, as well
      as in two ccRCC cell lines (Caki-1 and Caki-2). CcRCC specimens contained 12-fold
      higher mRNA levels of KCa3.1 than oncocytoma specimens. The large-conductance
      channel, KCa1.1, was 3-fold more highly expressed in ccRCC than in oncocytoma.
      KCa3.1 mRNA expression in ccRCC was 2-fold higher than in the healthy cortex of
      the same kidney. Disease specific survival trended towards reduction in the
      subgroup of high-KCa3.1-expressing tumors (p<0.08 vs. low-KCa3.1-expressing
      tumors). Progression-free survival (time to metastasis/recurrence) was reduced
      significantly in the subgroup of high-KCa3.1-expressing tumors (p<0.02, vs. low
      KCa3.1-expressing tumors). Immunohistochemistry revealed high protein expression
      of KCa3.1 in tumor vessels of ccRCC and oncocytoma and in a subset of ccRCC
      cells. Oncocytoma cells were devoid of KCa3.1 protein. In a primary ccRCC cell
      line and Caki-1/2-ccRCC cells, we found KCa3.1-protein as well as TRAM-34
      sensitive KCa3.1-currents in a subset of cells. Furthermore, Caki-1/2-ccRCC cells
      displayed functional Paxilline-sensitive KCa1.1 currents. Neither KCa3.1 nor
      KCa1.1 were found in a primary oncocytoma cell line. Yet KCa-blockers, like TRAM
      34 (KCa3.1) and Paxilline (KCa1.1), had no appreciable effects on Caki-1
      proliferation in-vitro. CONCLUSIONS/SIGNIFICANCE: Our study demonstrated
      expression of KCa3.1 in ccRCC but not in benign oncocytoma. Moreover, high KCa3.1
      mRNA expression levels were indicative of low disease specific survival of ccRCC
      patients, short progression-free survival, and a high metastatic potential.
      Therefore, KCa3.1 is of prognostic value in ccRCC.

PMID- 25848766
TI  - Genomic heterogeneity of osteosarcoma - shift from single candidates to
      functional modules.
AB  - Osteosarcoma (OS), a bone tumor, exhibit a complex karyotype. On the genomic
      level a highly variable degree of alterations in nearly all chromosomal regions
      and between individual tumors is observable. This hampers the identification of
      common drivers in OS biology. To identify the common molecular mechanisms
      involved in the maintenance of OS, we follow the hypothesis that all the copy
      number-associated differences between the patients are intercepted on the level
      of the functional modules. The implementation is based on a network approach
      utilizing copy number associated genes in OS, paired expression data and protein
      interaction data. The resulting functional modules of tightly connected genes
      were interpreted regarding their biological functions in OS and their potential
      prognostic significance. We identified an osteosarcoma network assembling well
      known and lesser-known candidates. The derived network shows a significant
      connectivity and modularity suggesting that the genes affected by the
      heterogeneous genetic alterations share the same biological context. The network
      modules participate in several critical aspects of cancer biology like DNA damage
      response, cell growth, and cell motility which is in line with the hypothesis of
      specifically deregulated but functional modules in cancer. Further, we could
      deduce genes with possible prognostic significance in OS for further
      investigation (e.g. EZR, CDKN2A, MAP3K5). Several of those module genes were
      located on chromosome 6q. The given systems biological approach provides evidence
      that heterogeneity on the genomic and expression level is ordered by the
      biological system on the level of the functional modules. Different genomic
      aberrations are pointing to the same cellular network vicinity to form vital, but
      already neoplastically altered, functional modules maintaining OS. This
      observation, exemplarily now shown for OS, has been under discussion already for
      a longer time, but often in a hypothetical manner, and can here be exemplified
      for OS. 

PMID- 25848767
TI  - Baclofen, a GABABR agonist, ameliorates immune-complex mediated acute lung injury
      by modulating pro-inflammatory mediators.
AB  - Immune-complexes play an important role in the inflammatory diseases of the lung.
      Neutrophil activation mediates immune-complex (IC) deposition-induced acute lung
      injury (ALI). Components of gamma amino butyric acid (GABA) signaling, including
      GABA B receptor 2 (GABABR2), GAD65/67 and the GABA transporter, are present in
      the lungs and in the neutrophils. However, the role of pulmonary GABABR
      activation in the context of neutrophil-mediated ALI has not been determined.
      Thus, the objective of the current study was to determine whether administration
      of a GABABR agonist, baclofen would ameliorate or exacerbate ALI. We hypothesized
      that baclofen would regulate IC-induced ALI by preserving pulmonary GABABR
      expression. Rats were subjected to sham injury or IC-induced ALI and two hours
      later rats were treated intratracheally with saline or 1 mg/kg baclofen for 2
      additional hours and sacrificed. ALI was assessed by vascular leakage, histology,
      TUNEL, and lung caspase-3 cleavage. ALI increased total protein, tumor necrosis
      factor alpha (TNF-alpha and interleukin-1 receptor associated protein (IL-1R
      AcP), in the bronchoalveolar lavage fluid (BALF). Moreover, ALI decreased lung
      GABABR2 expression, increased phospho-p38 MAPK, promoted IkappaB degradation and
      increased neutrophil influx in the lung. Administration of baclofen, after
      initiation of ALI, restored GABABR expression, which was inhibited in the
      presence of a GABABR antagonist, CGP52432. Baclofen administration activated
      pulmonary phospho-ERK and inhibited p38 MAPK phosphorylation and IkappaB
      degradation. Additionally, baclofen significantly inhibited pro-inflammatory TNF
      alpha and IL-1betaAcP release and promoted BAL neutrophil apoptosis. Protective
      effects of baclofen treatment on ALI were possibly mediated by inhibition of TNF
      alpha- and IL-1beta-mediated inflammatory signaling. Interestingly, GABABR2
      expression was regulated in the type II pneumocytes in lung tissue sections from
      lung injured patients, further suggesting a physiological role for GABABR2 in the
      repair process of lung damage. GABABR2 agonists may play a potential therapeutic
      role in ALI. 

PMID- 25848769
TI  - Home sampling for sexually transmitted infections and HIV in men who have sex
      with men: a prospective observational study.
AB  - To determine uptake of home sampling kit (HSK) for STI/HIV compared to clinic
      based testing, whether the availability of HSK would increase STI testing rates
      amongst HIV infected MSM, and those attending a community-based HIV testing
      clinic compared to historical control. Prospective observational study in three
      facilities providing STI/HIV testing services in Brighton, UK was conducted.
      Adult MSM attending/contacting a GUM clinic requesting an STI screen (group 1),
      HIV infected MSM attending routine outpatient clinic (group 2), and MSM attending
      a community-based rapid HIV testing service (group 3) were eligible. Participants
      were required to have no symptomatology consistent with STI and known to be
      immune to hepatitis A and B (group 1). Eligible men were offered a HSK to obtain
      self-collected specimens as an alternative to routine testing. HSK uptake
      compared to conventional clinic-based STI/HIV testing in group 1, increase in STI
      testing rates due to availability of HSK compared to historical controls in group
      2 and 3, and HSK return rates in all settings were calculated. Among the 128
      eligible men in group 1, HSK acceptance was higher (62.5% (95% CI: 53.5-70.9))
      compared to GUM clinic-based testing (37.5% (95% CI: 29.1-46.5)), (p = 0.0004).
      Two thirds of eligible MSM offered an HSK in all three groups accepted it, but
      HSK return rates varied (highest in group 1, 77.5%, lowest in group 3, 16%). HSK
      for HIV testing was acceptable to 81% of men in group 1. Compared to historical
      controls, availability of HSK increased the proportion of MSM testing for STIs in
      group 2 but not in group 3. HSK for STI/HIV offers an alternative to conventional
      clinic-based testing for MSM seeking STI screening. It significantly increases
      STI testing uptake in HIV infected MSM. HSK could be considered as an adjunct to
      clinic-based services to further improve STI/HIV testing in MSM. 

PMID- 25848768
TI  - Ketones prevent oxidative impairment of hippocampal synaptic integrity through
      KATP channels.
AB  - Dietary and metabolic therapies are increasingly being considered for a variety
      of neurological disorders, based in part on growing evidence for the
      neuroprotective properties of the ketogenic diet (KD) and ketones. Earlier, we
      demonstrated that ketones afford hippocampal synaptic protection against
      exogenous oxidative stress, but the mechanisms underlying these actions remain
      unclear. Recent studies have shown that ketones may modulate neuronal firing
      through interactions with ATP-sensitive potassium (KATP) channels. Here, we used
      a combination of electrophysiological, pharmacological, and biochemical assays to
      determine whether hippocampal synaptic protection by ketones is a consequence of
      KATP channel activation. Ketones dose-dependently reversed oxidative impairment
      of hippocampal synaptic integrity, neuronal viability, and bioenergetic capacity,
      and this action was mirrored by the KATP channel activator diazoxide. Inhibition
      of KATP channels reversed ketone-evoked hippocampal protection, and genetic
      ablation of the inwardly rectifying K+ channel subunit Kir6.2, a critical
      component of KATP channels, partially negated the synaptic protection afforded by
      ketones. This partial protection was completely reversed by co-application of the
      KATP blocker, 5-hydoxydecanoate (5HD). We conclude that, under conditions of
      oxidative injury, ketones induce synaptic protection in part through activation
      of KATP channels. 

PMID- 25848770
TI  - Membrane bound GSK-3 activates Wnt signaling through disheveled and arrow.
AB  - Wnt ligands and their downstream pathway components coordinate many developmental
      and cellular processes. In adults, they regulate tissue homeostasis through
      regulation of stem cells. Mechanistically, signal transduction through this
      pathway is complicated by pathway components having both positive and negative
      roles in signal propagation. Here we examine the positive role of GSK-3/Zw3 in
      promoting signal transduction at the plasma membrane. We find that targeting GSK
      3 to the plasma membrane activates signaling in Drosophila embryos. This
      activation requires the presence of the co-receptor Arrow-LRP5/6 and the pathway
      activating protein Disheveled. Our results provide genetic evidence for
      evolutionarily conserved, separable roles for GSK-3 at the membrane and in the
      cytosol, and are consistent with a model where the complex cycles from cytosol to
      membrane in order to promote signaling at the membrane and to prevent it in the
      cytosol. 

PMID- 25848771
TI  - A multi-layered protein network stabilizes the Escherichia coli FtsZ-ring and
      modulates constriction dynamics.
AB  - The prokaryotic tubulin homolog, FtsZ, forms a ring-like structure (FtsZ-ring) at
      midcell. The FtsZ-ring establishes the division plane and enables the assembly of
      the macromolecular division machinery (divisome). Although many molecular
      components of the divisome have been identified and their interactions
      extensively characterized, the spatial organization of these proteins within the
      divisome is unclear. Consequently, the physical mechanisms that drive divisome
      assembly, maintenance, and constriction remain elusive. Here we applied single
      molecule based superresolution imaging, combined with genetic and biophysical
      investigations, to reveal the spatial organization of cellular structures formed
      by four important divisome proteins in E. coli: FtsZ, ZapA, ZapB and MatP. We
      show that these interacting proteins are arranged into a multi-layered protein
      network extending from the cell membrane to the chromosome, each with unique
      structural and dynamic properties. Further, we find that this protein network
      stabilizes the FtsZ-ring, and unexpectedly, slows down cell constriction,
      suggesting a new, unrecognized role for this network in bacterial cell division.
      Our results provide new insight into the structure and function of the divisome,
      and highlight the importance of coordinated cell constriction and chromosome
      segregation. 

PMID- 25848772
TI  - How long can stool samples be fixed for an accurate diagnosis of soil-transmitted
      helminth infection using Mini-FLOTAC?
AB  - BACKGROUND: Kato-Katz is a widely used method for the diagnosis of soil
      transmitted helminth infection. Fecal samples cannot be preserved, and hence,
      should be processed on the day of collection and examined under a microscope
      within 60 min of slide preparation. Mini-FLOTAC is a technique that allows
      examining fixed fecal samples. We assessed the performance of Mini-FLOTAC using
      formalin-fixed stool samples compared to Kato-Katz and determined the dynamics of
      prevalence and intensity estimates of soil-transmitted helminth infection over a
      31-day time period. METHODOLOGY: The study was carried out in late 2013 on Pemba
      Island, Tanzania. Forty-one children were enrolled and stool samples were
      subjected on the day of collection to a single Kato-Katz thick smear and Mini
      FLOTAC examination; 12 aliquots of stool were fixed in 5% formalin and
      subsequently examined by Mini-FLOTAC up to 31 days after collection. PRINCIPAL
      FINDINGS: The combined results from Kato-Katz and Mini-FLOTAC revealed that 100%
      of children were positive for Trichuris trichiura, 85% for Ascaris lumbricoides,
      and 54% for hookworm. Kato-Katz and Mini-FLOTAC techniques found similar
      prevalence estimates for A. lumbricoides (85% versus 76%), T. trichiura (98%
      versus 100%), and hookworm (42% versus 51%). The mean eggs per gram of stool
      (EPG) according to Kato-Katz and Mini-FLOTAC was 12,075 and 11,679 for A.
      lumbricoides, 1,074 and 1,592 for T. trichiura, and 255 and 220 for hookworm,
      respectively. The mean EPG from day 1 to 31 of fixation was stable for A.
      lumbricoides and T. trichiura, but gradually declined for hookworm, starting at
      day 15. CONCLUSIONS/SIGNIFICANCE: The findings of our study suggest that for a
      qualitative diagnosis of soil-transmitted helminth infection, stool samples can
      be fixed in 5% formalin for at least 30 days. However, for an accurate
      quantitative diagnosis of hookworm, we suggest a limit of 15 days of
      preservation. Our results have direct implication for integrating soil
      transmitted helminthiasis into transmission assessment surveys for lymphatic
      filariasis.

PMID- 25848774
TI  - Correction: The alpha1,6-fucosyltransferase gene (fut8) from the Sf9 lepidopteran
      insect cell line: insights into fut8 evolution.

PMID- 25848773
TI  - Self-regulation of brain activity in patients with postherpetic neuralgia: a
      double-blind randomized study using real-time FMRI neurofeedback.
AB  - BACKGROUND: A pilot study has shown that real-time fMRI (rtfMRI) neurofeedback
      could be an alternative approach for chronic pain treatment. Considering the
      relative small sample of patients recruited and not strictly controlled
      condition, it is desirable to perform a replication as well as a double-blinded
      randomized study with a different control condition in chronic pain patients.
      Here we conducted a rtfMRI neurofeedback study in a subgroup of pain patients -
      patients with postherpetic neuralgia (PHN) and used a different sham
      neurofeedback control. We explored the feasibility of self-regulation of the
      rostral anterior cingulate cortex (rACC) activation in patients with PHN through
      rtfMRI neurofeedback and regulation of pain perception. METHODS: Sixteen patients
      (46-71 years) with PHN were randomly allocated to a experimental group (n = 8) or
      a control group (n = 8). 2 patients in the control group were excluded for large
      head motion. The experimental group was given true feedback information from
      their rACC whereas the control group was given sham feedback information from
      their posterior cingulate cortex (PCC). All subjects were instructed to perform
      an imagery task to increase and decrease activation within the target region
      using rtfMRI neurofeedback. RESULTS: Online analysis showed 6/8 patients in the
      experimental group were able to increase and decrease the blood oxygen level
      dependent (BOLD) fMRI signal magnitude during intermittent feedback training.
      However, this modulation effect was not observed in the control group. Offline
      analysis showed that the percentage of BOLD signal change of the target region
      between the last and first training in the experimental group was significantly
      different from the control group's and was also significantly different than 0.
      The changes of pain perception reflected by numerical rating scale (NRS) in the
      experimental group were significantly different from the control group. However,
      there existed no significant correlations between BOLD signal change and NRS
      change. CONCLUSION: Patients with PHN could learn to voluntarily control over
      activation in rACC through rtfMRI neurofeedback and alter their pain perception
      level. The present study may provide new evidence that rtfMRI neurofeedback
      training may be a supplemental approach for chronic clinical pain management.

PMID- 25848775
TI  - Association between perfluorinated compound exposure and miscarriage in Danish
      pregnant women.
AB  - Perfluorinated alkylated substances (PFAS) have been extensively used in consumer
      products and humans are widely exposed to these persistent compounds. A recent
      study found no association between exposure to perfluorooctanoic acid (PFOA) and
      perfluorooctanesulfonic acid (PFOS) and miscarriage, but no studies have examined
      adverse effect of the more recently introduced PFASs. We therefore conducted a
      case-control study within a population-based, prospective cohort during 2010
      2012. Newly pregnant women residing in the Municipality of Odense, Denmark were
      invited to enroll in the Odense Child Cohort at their first antenatal visit
      before pregnancy week 12. Among a total of 2,874 participating women, 88 suffered
      a miscarriage and 59 had stored serum samples, of which 56 occurred before
      gestational week 12. They were compared to a random sample (N=336) of delivering
      women, who had also donated serum samples before week 12. Using a case-control
      design, 51 of the women suffering a miscarriage were matched on parity and
      gestational day of serum sampling with 204 delivering women. In a multiple
      logistic regression with adjustment for age, BMI, parity and gestational age at
      serum sampling, women with the highest tertile of exposure to perfluorononanoic
      acid (PFNA) and perfluorodecanoic acid (PFDA) in pregnancy had odds ratios for
      miscarriage of 16.5 (95% CI 7.4-36.6-36.5) and 2.67 (1.31-5.44), respectively, as
      compared to the lowest tertile. In the matched data set, the OR were 37.9 (9.9
      145.2) and 3.71 (1.60-8.60), respectively. The association with perfluorohexane
      sulfonic acid (PFHxS) was in the same direction, but not statistically
      significant, while no association was found with PFOA and PFOS. Our findings
      require confirmation due to the possible public health importance, given that all
      pregnant women are exposed to these widely used compounds. 

PMID- 25848776
TI  - Anatomically discrete sex differences in neuroplasticity in zebra finches as
      reflected by perineuronal nets.
AB  - Large morphological sex differences in the vertebrate brain were initially
      identified in song control nuclei of oscines. Besides gross differences between
      volumes of nuclei in males and females, sex differences also concern the size and
      dendritic arborization of neurons and various neurochemical markers, such as the
      calcium-binding protein parvalbumin (PV). Perineuronal nets (PNN) of the
      extracellular matrix are aggregates of different compounds, mainly chondroitin
      sulfate proteoglycans, that surround subsets of neurons, often expressing PV. PNN
      develop in zebra finches song control nuclei around the end of the sensitive
      period for song learning and tutor deprivation, known to delay the end of the
      song learning sensitive period, decreases the numbers of PNN in HVC. We
      demonstrate here the existence in zebra finches of a major sex difference (males
      > females) affecting the number of PNN (especially those surrounding PV-positive
      cells) in HVC and to a smaller extent the robust nucleus of the arcopallium, RA,
      the two main nuclei controlling song production. These differences were not
      present in Area X and LMAN, the lateral magnocellular nucleus of the anterior
      nidopallium. A dense expression of material immunoreactive for chondroitin
      sulfate was also detected in several nuclei of the auditory and visual pathways.
      This material was often organized in perineuronal rings but quantification of
      these PNN did not reveal any sex difference with the exception that the
      percentage of PNN surrounding PV-ir cells in the dorsal lateral mesencephalic
      nucleus, MLd, was larger in females than in males, a sex difference in the
      opposite direction compared to what is seen in HVC and RA. These data confirm and
      extend previous studies demonstrating the sex difference affecting PNN in HVC-RA
      by showing that this sex difference is anatomically specific and does not concern
      visual or auditory pathways. 

PMID- 25848777
TI  - Circumpapillary course of retinal pigment epithelium can be fit to sine wave and
      amplitude of sine wave is significantly correlated with ovality ratio of optic
      disc.
AB  - The purpose of this study was to develop a method of quantifying the degree of
      optic disc tilt in normal eyes. This was a prospective, observational cross
      sectional study of 126 right eyes of 126 healthy volunteers. The optic disc tilt
      was determined from the circular peripapillary optical coherence tomographic
      (OCT) scan images. The course of the retinal pigment epithelium (RPE) layer in
      the peripapillary cross sectional scan images was fit to a sine wave curve, and
      the amplitude of the sine curve was used to reflect the degree of the optic disc
      tilt in the optical axis. The repeatability of the amplitude determinations was
      calculated. The correlation between the amplitude and the ovality ratio of the
      optic disc was determined. The correlation between the amplitude and the body
      height was also calculated. The mean amplitude was 36.6 +/- 17.5 pixels, which
      was significantly and inversely correlated with the ovality ratio of the optic
      disc (R = -0.59, P < 0.001). The intra-rater and inter-rater correlation
      coefficients of the amplitude were significant high (P < 0.001, both). The
      amplitude was significantly and inversely correlated with the body height (R = 
      0.38, P < 0.001), but not with the axial length. In conclusion, a sine wave
      function can be used to describe the course of the RPE in the circumpapillary OCT
      images. The results indicate that the amplitude of the sine wave can be used to
      represent the degree of optic disc tilt. Thus, the sine wave analyses can be used
      as a quantifiable and repeatable method to determine the optic disc tilt.

PMID- 25848778
TI  - Diet and cancer risk/association between diet and risk of cancer.
AB  - The article discusses problem of the association between diet and risk of cancer.
      Author shows methodological concerns arising from the difficulty of selecting the
      study groups, and also those dependent on ascertainment of the composition of the
      diet for a long period of time necessary to establish the statistical
      associations. Sources of carcinogenic substances in food include environmental
      contaminants, chemicals synthesized in some plants and those which infiltrate the
      food or are produced during the food processing. It is strongly advisable to
      limit the content of carcinogenic substances in food by imposing Regulation (EC)
      No 1881/2006 not only regarding products exported to the EU countries, but also
      those intended for local market.

PMID- 25848779
TI  - Food supplement-related risks in the light of internet and RASFF data.
AB  - OBJECTIVE: Based on legal acts and RASFF information, this paper aimed at
      evaluating available facts on food supplements in comparison to the most popular
      data accessible via Internet for future and present consumers. MATERIAL AND
      METHODS: Having analyzed legal acts and RASFF (Rapid Alert System for Food and
      Feed) database, the authors attempted to verify what kind of information on food
      supplements may be found by an Internet user, using the first webpage of
      Google.pl. This search engine was used in this study as it gained the highest
      popularity among Internet users. It was decided that exclusively search results
      displayed on the first webpage would be subject to analysis as 91.5% of Internet
      users limit their search to the first 9-10 results. Internet was searched using
      the following two terms: 'supplement' and 'supplements' as well as terms
      suggested by Google. pl. Subsequently, the results were subject to qualitative
      and quantitative analyses. RESULTS: On the Internet, the most frequently searched
      terms were: 'supplements' (243 000 000), 'supplement' (9 290 000), 'supplements
      shop' (8 200 000). Having analyzed the content of particular websites,
      information on certain products, given by their manufacturers may be found. Then,
      data on supplement itself were provided, i.e. what is a supplement and when it
      should be used. Expert articles (written by physicians, dieticians, pharmacists)
      on a risk resulting from these products, including therapeutic indications or the
      presence of unauthorized substances were identified considerably less frequently.
      No warnings regarding the necessity of purchasing the products in legal and
      verified places were found. CONCLUSIONS: There is a necessity of systemic
      education of consumers on reasonable use of food supplements. It is also
      advisable to consider the organization of alert system whose objective would be
      to monitor adverse reactions caused by an intake of food supplements or novel
      food launched into the country. To obtain reliable information on the composition
      and effects of food supplements, potential consumer should contact physician or
      dietician. Additionally, complementary information, using different sources with
      an example being health-related portals, presenting articles written by
      physicians or pharmacists, may be also searched.

PMID- 25848780
TI  - An isolated outbreak of influenza A H1N1 in a haematological department during
      post-pandemic period.
AB  - INTRODUCTION AND OBJECTIVE: Influenza A H1N1 virus strain was associated with the
      pandemic outbreak of febrile respiratory infections worldwide in 2009, however in
      August 2010, the WHO announced that the world had entered the postpandemic
      period. It offered specific recommendations for this period, including the
      identification of clusters of severe respiratory disorders and deaths. Here we
      report the fulminant course of influenza AH1N1 infection in the postpandemic
      period in a group of patients in a single hematology department. We make an
      attempt to identify potential risk factors and the mode of spreading, and to
      provide recommendations for best practice. MATERIAL AND METHODS: We conducted a
      retrospective analysis of a cluster of patients diagnosed with or suspected of
      influenza A H1N1 infection in the period from December 2010 to March 2011.
      RESULTS: Fourteen patients with hematological disorders unexpectedly developed
      acute respiratory failure ARDS (Acute Respiratory Distress Syndrome). Of them,
      nine tested positive for influenza A H1N1 in a screening test and eight in
      confirmatory polymerase chain reaction. The infection was fatal in nine patients,
      despite artificial ventilation in eight and oseltamivir administration in 11. Ten
      were in reverse isolation according to CDC. No similar cases occurred in the
      whole hospital concurrently, or in the hematology wards at any other time.
      CONCLUSIONS: The occurrence of A H1N1 epidemics in a hematological ward in the
      post-pandemic period highlights the importance of awareness of this complication,
      prompt testing and antiviral treatment. Furthermore, it confirms the importance
      of vaccinating patients and personnel against influenza as a prophylactic
      measure.

PMID- 25848781
TI  - Non-influenza viruses in acute respiratory infections among young children. High
      prevalence of HMPV during the H1N1V.2009 pandemic in Poland.
AB  - In Poland the majority of hospitalized cases of pneumonia (annually more than
      70000) were reported without determination of an aetiological agent (J18 of ICD
      10), also because diagnosis of viral ARTI is limited to identification of
      influenza viruses or sometimes RSV. MATERIAL AND METHODS: For determination the
      contribution of non-influenza viruses in ARTI among children, 381 nasopharyngeal
      swabs from hospitalized in period X.2008-IV.2011y. children (aged 1 day - 5 y.o.)
      were tested for RSV, HMPV, HEV/HRV, HPIV 1-3, HAdV, HBoV. RESULTS: At least one
      viral agent was detected in 72.7% of patients. The most predominant was RSV
      infection (49%), followed by HEV/HRV (15.5%); HMPV (8.7%), Adenoviruses (7.4%),
      HPIVt.1-3 (5.8%) and HBoV (5.5%). Seven periods based on the median of examined
      children/month were determined: 3 with increased number of ARTI. RSV infections,
      diagnosed in all periods, were predominate in five periods, mainly in LRTI cases.
      In the 3th period - HMPV was predominant, in the 5th - HEV/HRV. It was found that
      clinical manifestation of HMPV infections varied depending on the period.
      CONCLUSIONS: Relatively high prevalence of HBoV or HMPV cases of ARTI, especially
      different clinical picture in some periods (ARTI without pneumonia or
      bronchiolitis), indicated necessary of more detailed molecular and
      epidemiological studies. Also our results indicate the need for improved
      diagnostic capabilities of virological tests in acute upper and lower respiratory
      tract infections in children.

PMID- 25848782
TI  - Usefulness of laboratory methods in diagnosis of pertussis in adult with
      paroxysmal cough.
AB  - INTRODUCTION: Pertussis is an acute, highly contagious bacterial infection of
      respiratory system caused by Bordetella pertussis. Principally, disease affects
      young children, however, recently it is also reported in adolescents and adults.
      Symptoms of pertussis in adults are non-specific, i.e. dry, paroxysmal and
      protracted cough. Thus, it is rarely diagnosed in this group. AIM: This paper
      aimed at evaluating the usefulness of the laboratory methods in diagnosis of
      pertussis in adults based on a case presenting with dry, paroxysmal and chronic
      cough. MATERIAL AND METHODS: Sputum (collected on 25th January 2013) and paired
      serum samples (collected on 13th February and 19 April 2013) were tested.
      Pertussis diagnostics involved culture, in-house PCR, real-time PCR and ELISA.
      RESULTS: Sputum culture, using commercial medium Bordetella Selective Medium by
      Oxoid did not reveal the presence of B. pertussis. Real-time PCR and PCR,
      however, confirmed the presence of insertion sequence IS481 and pertussis toxin
      promoter sequence ptx-Pr, markers indicative of B. pertussis infection.
      Serological testing revealed the high titres of IgA, IgG and IgM antibodies to B.
      pertussis in the first sample. In the second sample, collected 2 months following
      the first one, a significant decrease in IgA antibodies was reported.
      CONCLUSIONS: These data suggest a high usefulness of the laboratory methods in
      the diagnosis of pertussis in adults with chronic cough. Application of such
      methods ensures adequate diagnosis of disease, quick introduction of proper
      treatment and implementation of procedures preventing the spread of infection.

PMID- 25848783
TI  - Risk factors for tuberculosis and specific manifestations of disease.
AB  - In countries with good epidemiological situation, incidence of tuberculosis (TB)
      is relatively high in immigrants, prisoners, the homeless and unemployed. In a
      number of regions, co-infection of Mycobacterium tuberculosis and HIV raises
      difficulties in controlling TB epidemic. A problematic issue is also drug
      resistance, especially in the countries of the former Union of Soviet Socialist
      Republics (USSR). Neither co-infection of M.tuberculosis and HIV nor drug
      resistance are of special concern in Poland. Incidence of extrapulmonary TB is
      very diverse (6-44%), however, in Poland such manifestation of tuberculosis is
      diagnosed rarely. There is a necessity of monitoring local epidemiological trends
      and developing appropriate diagnostic and therapeutic models for better control
      of infection.

PMID- 25848784
TI  - Cerebrospinal fluid interleukin-6 concentration in patients with purulent,
      bacterial meningitis - own observations.
AB  - AIM: This study aimed at evaluating the usefulness of determining cerebrospinal
      fluid (CSF) interleukin-6 (IL-6) concentration in adults with purulent, bacterial
      meningoencephalitis. MATERIALAND METHODS: A study group consisted of 16 patients
      hospitalized in the Department of Infectious Diseases of the Medical University
      of Silesia in Bytom in 2008 - 2012 due to purulent, bacterial
      meningoencephalitis. All of them were classified into two groups based on
      clinical severity, assessed on admission: group I - severe condition, group II -
      moderately severe or mild condition. CSF IL-6 concentration was measured in all
      patients on the first day of hospitalization. RESULTS: Mean concentrations of IL
      6 in CSF were assessed at 391.54 pg/mL and 110.51 pg/mL in patients in severe
      (group I) and moderately severe or mild condition (group II), respectively.
      Differences between CSF mean concentrations of this cytokine in both groups were
      statistically significant (p<0.01). No correlations between CSF IL-6
      concentrations and other CSF inflammatory parameters were determined. Control
      testing performed in 5 patients of group I revealed only slight decrease of CSF
      IL-6 concentration in fatal cases. In case of patients who recovered from
      disease, IL-6 concentration in CSF was evidently decreased compared to its
      initial value. CONCLUSIONS: Results suggest the usefulness of determining CSF
      interleukin-6 concentration to estimate inflammation intensity in the
      subarachnoid space, and indirectly, patient's clinical severity. IL-6
      concentration may be also of prognostic importance in purulent, bacterial
      meningoencephalitis.

PMID- 25848785
TI  - Imported cases of dengue in Poland and their diagnosis.
AB  - Infections with dengue virus are transmitted by mosquitoes. In tropical areas, it
      is mainly spread by Aedes aegypti while in countries with lower temperatures by
      Aedes albopictus. Since 2010, autochthonous cases of dengue are also reported in
      Europe. There are 4 serotypes of dengue virus (DENV). No correlation between
      clinical presentation of disease and virus type, however, were determined.
      Nevertheless, reinfection with different type of DENV may lead to a serious, life
      threatening condition. An estimated 100 million persons are infected with dengue
      virus per year. Of them, approximately a half (mainly children) develop the
      symptoms of dengue fever (DF), dengue haemorrhagic fever (DHF) or dengue shock
      syndrome (DSS). Fatality is high in case of severe dengue. Dengue is a serious
      condition provided there is a presence of IgG antibodies directed against
      antigens of particular DENV serotypes, associated with primary infection caused
      by different serotype or transferred from infected mother to her child. For
      adequate dengue laboratory diagnosis, it is required to apply a set of various
      diagnostic methods. Within the family Flaviviridae, cross-reactivity is reported,
      which may lead to the occurrence of false-positive results. In Poland,
      differential diagnosis with different Flavivirus species is of special importance
      as it is an endemic area for tick-borne encephalitis (TBE). Thus, data regarding
      history of patient's immunization against TBE or yellow fever should be also
      taken into consideration as important in interpretation of results of serological
      examination.

PMID- 25848786
TI  - Retrospective review of the case of cutaneous anthrax-malignant pustule from 1995
      in 15-year old girl.
AB  - A 15-year-old girl was admitted to our Department with cutaneous lesion
      resembling black eschar. Anamnesis revealed that before getting ill she was
      wearing pullover made of rough sheep's wool and ornaments made of leather like
      straps. Cutaneous anthrax was confirmed by identification of B. anthracis in
      specimens from weeping ulceration, culture from black eschar, thermoprecipitation
      test, and bioassay on guinea pig. The girl was treated with crystalline
      Penicillin. She responded well to the therapy and recovered after 28 days. What
      attracts attention in presented case is the fact that the girl didn't belong to
      high risk group of human anthrax, which might lead to misdiagnosis. In 1990-1999,
      Poland there were reported 22 cases of anthrax - it was almost exclusively
      cutaneous form. In the years following 1999 antrax was reported even less often -
      in the period 1991-2013 it was recorded a total of 26 cutaneous anthrax cases.

PMID- 25848787
TI  - Prevalence of gastrointestinal system infections acquired in Provincial Hospital
      in 2004-2013.
AB  - INTRODUCTION: Gastrointestinal system infection (GI) is an infection which is
      frequently acquired in health- care settings. In Poland, there are limited data
      on the distribution of gastrointestinal system infections in the epidemiology of
      healthcare-associated infections (HAIs). Therefore, a study was initiated with
      the objective to assess the prevalence and distribution of healthcare-associated
      gastrointestinal system infections in patients hospitalized in St. Lukas
      Provincial Hospital in Tarnow. MATERIALAND METHODS: Data of 297,545 patients
      hospitalized in 2004-2013 were subject to analysis. Standard epidemiological
      methods and unified definitions of healthcare-associated infections issued by the
      European Centre for Disease Prevention and Control (ECDC) were employed in the
      analysis. RESULTS: A total of 944 healthcare-associated gastrointestinal system
      infections were indentified in the material analyzed. In a 10-year observation of
      HAI prevalence, GIs predominated over other HAIs registered in St. Lukas
      Provincial Hospital in Tarnow. Cumulative incidence rate (CIR) and incidence
      density rate (IDR) for GIs were 0.35% and 0.57/1,000 person-days, respectively.
      Infections with Clostridium difficile (GI-CDI), also referred to as C. difficile
      associated diarrhoea (CDAD) were diagnosed in 301 patients. For GI-CDI, CIR and
      IDR were 0.11% and 0.18/1,000 person-days, respectively. Gastroenteritis
      excluding CDI (GI-GE) was identified in 643 patients with CIR and IDR amounting
      to 0.24% and 0.39/1,000 person-days, respectively. Gastroenteritis of rotavirus
      (CIR - 0.11% and IDR - 0.18/1,000), adenovirus (CIR - 0.01% and IDR - 0.02/1,000)
      and norovirus (CIR - 0.01% and IDR - 0.01/1,000) etiology was identified in 292,
      32 and 17 patients, respectively. The highest number of infections was reported
      in paediatric ward, i.e. 307 persons (32.5%) (CIR - 1.84% and IDR - 2.79/1,000)
      and internal medicine and nephrology ward - 202 infections (21.4%) (CIR - 1.47%
      and IDR - 1.66/1,000). CONCLUSIONS: A 10-year observation of healthcare
      associated infections showed a change in the distribution of HAIs. In recent
      years, GIs predominated over all infections acquired in healthcare settings. The
      most prevalent etiological agent identified was Clostridium difficile.

PMID- 25848788
TI  - Three-step diagnostic algorithm in diagnosing patients suspected of Clostridium
      difficile-associated diarrhea.
AB  - Clostridium difficile is a predominant etiological agent of healthcare-associated
      infectious diarrhea. Immunoenzymatic tests for detecting toxins A/B from faecal
      samples are still used in routine diagnosis of Clostridium difficile-associated
      diseases in a number of healthcare centers in Poland. Recently, however, new
      diagnostic tests were introduced which allow for detecting toxigenic strains of
      C. difficile in a more effective and precise manner. It is of importance,
      especially in the light of hypervirulent strain occurrence. AIM: The aim of the
      present paper was to evaluate the efficacy of three-step algorithm in the
      diagnosis of Clostridium difficile-associated diseases (CDAD), considering the
      occurrence of false negative test results for toxins while using exclusively
      immunoenzymatic tests. MATERIALS AND METHODS: In the present study, faecal
      samples collected from patients presenting diarrhea were tested. Immunoenzymatic
      tests were used for detecting glutamate dehydrogenase (GDH) and toxins A/B.
      Culture and RT-PCR were also employed. RESULTS: Of 615 study participants,
      toxigenic strains GDH (+) TOX (+) were identified in 108 patients while for 67
      patients, test results remained unspecified GDH (+) TOX (-). Further analysis of
      unspecified samples revealed 32 patients infected with toxigenic strains, i.e.
      22.9% of all positive test results (n=140). CONCLUSION: Three-step diagnostic
      algorithm is an effective and reliable tool for diagnosing C.difficile-
      associated diseases.

PMID- 25848789
TI  - Perinatal mortality in urban and rural areas in Poland in 2002-2012.
AB  - AIM: The aim of this study was to analyze the level and trends of perinatal
      mortality by mother's place of residence (urban vs rural area) in Poland in 2002
      2012. MATERIAL AND METHOD: This study was based on the data of the Central
      Statistical Office on the number of live births, infant deaths (0-6 days) and
      stillbirths by mother's place of residence (urban vs rural area), reported in
      2002-2012 in 16 provinces and Poland in general. Joinpoint model was used to
      analyze perinatal mortality rate trends over time and average annual percent
      change (APC). Urban/rural ratio was employed to demonstrate the differences in
      perinatal mortality between urban and rural areas. RESULTS: In the period
      analyzed, perinatal mortality in Poland decreased by 3.4% (p<0.05) and 2.7%
      (p<0.05) per year in urban and rural areas, respectively. Having considered urban
      areas, perinatal mortality rate was decreasing at the fastest pace in the
      following provinces: Pomorskie (APC) = -6.6%, p<0.05), Warminsko-Mazurskie (APC)
      = -5.4%, p<0.05), Lubuskie i Swietokrzyskie (APC = -4.5%, p<0.05) while for rural
      areas - Dolnoslaskie (APC = -4.3%, p<0.05), Wielkopolskie, Zachodniopomorskie
      (APC = -3.7%, p<0.05) and Slaskie (APC = -3.2%, p<0.05). CONCLUSIONS: In the
      study period, a decrease in perinatal mortality was reported in Poland, both in
      urban and rural areas. The level of perinatal mortality rate as well as the pace
      of these changes differed between provinces.

PMID- 25848790
TI  - Impact of biodiversity on tick-borne diseases.
AB  - It is a well-known fact that high biodiversity is related to the health and
      proper functioning of environment. Recently, the attempts to search the relations
      between biodiversity and human health are also undertaken. A number of studies
      demonstrate that people living in undegraded environment are less exposed to the
      diseases of affluence. However, they are at a higher risk of contracting
      zoonoses. It is believed that the higher the number of animals, the higher is the
      number of ticks. Consequently, there is a serious risk of borreliosis and other
      tick-borne diseases. Such assumption, however, may be erroneous. A number of
      studies suggest a decreasing prevalence of tick-borne disease pathogens in high
      biodiversity areas. In this paper, a promising hypothesis explaining this
      relation is discussed.

PMID- 25848791
TI  - Emergent management of scorpion sting.
AB  - Scorpionism (syndrome of scorpion stings) is an important public health problem
      in many regions of the world, not only in tropics and subtropics. As scorpions
      may be unintentionally transported to any place in the world and keeping
      scorpions as pets is becoming more popular, scorpion stings occur also in Poland.
      Therefore, health professionals should have the knowledge on the management of
      scorpion stings. This article discusses a case who was stung by scorpion and
      proposes an algorithm of management with such patients.

PMID- 25848792
TI  - Prevalence of dental erosion in young adults aged 18 years in Poland.
AB  - AIM: The aim of this study was to assess the prevalence of tooth wear in young
      adults in Poland. METHODS: A total of 1,886 persons aged 18 years, selected on a
      basis of multistage sampling, were examined within the Nationwide Dental Health
      Monitoring Programme. Previously calibrated dentists measured tooth wear using
      the BEWE-scoring system (Basic Erosive Wear Examination). RESULTS: Out of 1,886
      young adults, 42.2% presented the signs of dental erosion. Considered the
      severity of erosion, it was graded as 1, 2 and 3 in 28.9%, 11.9% and 1.5% of 18
      year-olds, respectively. CONCLUSIONS: Results of clinical assessment of dental
      erosion in 18-year-old young adults revealed that erosive tooth wear is an
      important problem in this age group. Of them, 13.4% had signs of advanced tooth
      wear which may lead to serious clinical problems in the future.

PMID- 25848793
TI  - Ludwik Hirszfeld in the National Institute of Hygiene in 1920-1941.
AB  - In this year, we commemorate the 130th anniversary of birth and 60th of death of
      Ludwik Hirszfeld, a prominent Polish scientist. Since 1920, he was the head of
      the Department of Bacteriology and Experimental Therapy of the National Institute
      of Hygiene (NIH). During the absence of Ludwik Rajchman in Poland, who was
      assigned to the League of Nations, he was a factual director of the NIH. Ludwik
      Hirszfeld governed the scientific, organizational and didactic activities in the
      Institute. Concurrently, he collaborated with research centres abroad, especially
      within the field of public health. Mission of the NIH was concentrated on a
      broadly defined issues aimed at combating infectious diseases, initiating and
      developing the production of sera and vaccines, their controlling and introducing
      to the country as well as training health care personnel. 

PMID- 25848794
TI  - Coordination of public institution response to a threat of epidemic.
AB  - Workshop held in the National Institute of Public Health - National Institute of
      Hygiene on 11th September 2014. 

PMID- 25848796
TI  - Correction: Incorporating cold-air pooling into downscaled climate models
      increases potential refugia for snow-dependent species within the Sierra Nevada
      Ecoregion, CA.

PMID- 25848795
TI  - Metabolic hormones, apolipoproteins, adipokines, and cytokines in the alveolar
      lining fluid of healthy adults: compartmentalization and physiological
      correlates.
AB  - OBJECTIVES: Our current understanding of hormone regulation in lung parenchyma is
      quite limited. We aimed to quantify a diverse array of biologically relevant
      protein mediators in alveolar lining fluid (ALF), compared to serum
      concentrations, and explore factors associated with protein compartmentalization
      on either side of the air-blood barrier. RESEARCH DESIGN AND METHODS:
      Participants were 24 healthy adult non-smoker volunteers without respiratory
      symptoms or significant medical conditions, with normal lung exams and office
      spirometry. Cell-free bronchoalveolar lavage fluid and serum were analyzed for 24
      proteins (including enteric and metabolic hormones, apolipoproteins, adipokines,
      and cytokines) using a highly sensitive multiplex ELISA. Measurements were
      normalized to ALF concentrations. The ALF:serum concentration ratios were
      examined in relation to measures of protein size, hydrophobicity, charge, and to
      participant clinical and spirometric values. RESULTS: ALF measurements from 24
      individuals detected 19 proteins, including adiponectin, adipsin, apoA-I, apoA
      II, apoB, apoC-II, apoC-III, apoE, C-reactive protein, ghrelin, glucose-dependent
      insulinotropic peptide (GIP), glucagon-like peptide-1 (GLP-1), glucagon, insulin,
      leptin, monocyte chemoattractant protein-1, plasminogen activator inhibitor-1,
      resistin, and visfatin. C-peptide and serpin E1 were not detected in ALF for any
      individual, and IL-6, IL-10, and TNF-alpha were not detected in either ALF or
      serum for any individual. In general, ALF levels were similar or lower in
      concentration for most proteins compared to serum. However, ghrelin, resistin,
      insulin, visfatin and GLP-1 had ALF concentrations significantly higher compared
      to serum. Importantly, elevated ALF:serum ratios of ghrelin, visfatin and
      resistin correlated with protein net charge and isoelectric point, but not with
      molecular weight or hydrophobicity. CONCLUSIONS: Biologically relevant enteric
      and metabolic hormones, apolipoproteins, adipokines, and cytokines can be
      detected in the ALF of healthy individuals. For the proteins measured, charge may
      influence trafficking and compartmentalization to the alveolar airspace more than
      molecular weight or hydrophobicity. These data may have implications for
      homeostasis and drug delivery to the lung.

PMID- 25848797
TI  - Cullin3-BTB interface: a novel target for stapled peptides.
AB  - Cullin3 (Cul3), a key factor of protein ubiquitination, is able to interact with
      dozens of different proteins containing a BTB (Bric-a-brac, Tramtrack and Broad
      Complex) domain. We here targeted the Cul3-BTB interface by using the intriguing
      approach of stabilizing the alpha-helical conformation of Cul3-based peptides
      through the "stapling" with a hydrocarbon cross-linker. In particular, by
      combining theoretical and experimental techniques, we designed and characterized
      stapled Cul3-based peptides embedding the helix 2 of the protein (residues 49
      68). Intriguingly, CD and NMR experiments demonstrate that these stapled peptides
      were able to adopt the helical structure that the fragment assumes in the parent
      protein. We also show that some of these peptides were able to bind to the BTB of
      the tetrameric KCTD11, a substrate adaptor involved in HDAC1 degradation, with
      high affinity (~ 300-600 nM). Cul3-derived staple peptides are also able to bind
      the BTB of the pentameric KCTD5. Interestingly, the affinity of these peptides is
      of the same order of magnitude of that reported for the interaction of full
      length Cul3 with some BTB containing proteins. Moreover, present data indicate
      that stapling endows these peptides with an increased serum stability.
      Altogether, these findings indicate that the designed stapled peptides can
      efficiently mimic protein-protein interactions and are potentially able to
      modulate fundamental biological processes involving Cul3. 

PMID- 25848799
TI  - Receding water line and interspecific competition determines plant community
      composition and diversity in wetlands in Beijing.
AB  - Climate and human-induced wetland degradation has accelerated in recent years,
      not only resulting in reduced ecosystem services but also greatly affecting the
      composition and diversity of wetland plant communities. To date, the knowledge of
      the differences in community parameters and their successional trends in degraded
      wetlands remains scarce. Here based on remote sensing images, geographic
      information system technology, and statistical methods, we produced a
      successional gradient map of the Yeyahu Wetland Nature Reserve in Beijing, which
      has experienced a steady decline in water level in recent decades. In addition,
      we analyzed community composition and diversity along with each identified
      gradient. The results showed that community diversity decreases while dominance
      increases with the progress of succession, with the highest diversity occurring
      during the early stage of succession. Moreover, the community demonstrates
      greater similarity among subareas during later successional stages, and the
      similarity coefficients calculated from the important value (IV) of each species
      are more accurate. Correlation analysis showed that the impact of soil factors on
      diversity was not significant at a subarea scale, although these nutrients showed
      an increasing trend with the community succession. Furthermore, the IVs of the
      dominant species had a particularly significant impact on diversity, showing a
      significantly negative correlation with diversity indices and a significantly
      positive correlation with dominance indices. Further analysis showed that the
      retreat of water level resulted from sustained drought and local human activities
      was a major extrinsic driving force resulting in observed differences in the
      community successional stages, which resulted in differences in community
      composition and diversity. On the other hand, interspecific competition was the
      main intrinsic mechanism, which significantly influenced the IVs of the dominant
      species and community diversity. The results of this study could aid in improving
      the understanding of community composition, diversity, and its successional
      trends in degraded wetlands. 

PMID- 25848798
TI  - Shigella infection interferes with SUMOylation and increases PML-NB number.
AB  - Shigellosis is a severe diarrheal disease that affects hundreds of thousands of
      individuals resulting in significant morbidity and mortality worldwide.
      Shigellosis is caused by Shigella spp., a gram-negative bacterium that uses a
      Type 3 Secretion System (T3SS) to deliver effector proteins into the cytosol of
      infected human cells. Shigella infection triggers multiple signaling programs
      that result in a robust host transcriptional response that includes the induction
      of multiple proinflammatory cytokines. PML nuclear bodies (PML-NBs) are dynamic
      subnuclear structures that coordinate immune signaling programs and have a
      demonstrated role in controlling viral infection. We show that PML-NB number
      increases upon Shigella infection. We examined the effects of Shigella infection
      on SUMOylation and found that upon Shigella infection the localization of
      SUMOylated proteins is altered and the level of SUMOylated proteins decreases.
      Although Shigella infection does not alter the abundance of SUMO activating
      enzymes SAE1 or SAE2, it dramatically decreases the level of the SUMO conjugating
      enzyme Ubc9. All Shigella-induced alterations to the SUMOylation system are
      dependent upon a T3SS. Thus, we demonstrate that Shigella uses one or more T3SS
      effectors to influence both PML-NB number and the SUMOylation machinery in human
      cells. 

PMID- 25848800
TI  - Unlocking patients with mental disorders who were in restraints at home: a
      national follow-up study of China's new public mental health initiatives.
AB  - BACKGROUND: In 2005, China implemented a demonstration program known as "686" to
      scale-up nation-wide basic mental health services designed to improve access to
      evidence-based care and to promote human rights for people with severe mental
      disorders. As part of the 686 Program, teams "unlocked" and provided continuous
      mental health care to people with severe mental disorders who were found in
      restraints and largely untreated in their family homes. We implemented a nation
      wide two-stage follow-up study to measure the effectiveness and sustainability of
      the "unlocking and treatment" intervention and its impact on the well-being of
      patients' families. METHODS: 266 patients unlocked from 2005 in "686"
      demonstration sites across China were recruited in Stage One of the study in
      2009. In 2012, 230 of the 266 cases were re-interviewed (the Stage Two study).
      Outcome measures included the patient medication adherence and social
      functioning, family burden ratings, and relocking rate. We utilized pre-post
      tests to analyze the changes over time following the unlocking efforts. RESULTS:
      96% of patients were diagnosed with schizophrenia. Prior to unlocking, their
      total time locked ranged from two weeks to 28 years, with 32% having been locked
      multiple times. The number of persons regularly taking medicines increased from
      one person at the time of unlocking to 74% in 2009 and 76% in 2012. Pre-post
      tests showed sustained improvement in patient social functioning and significant
      reductions in family burden. Over 92% of patients remained free of restraints in
      2012. CONCLUSION: Practice-based evidence from our study suggests an important
      model for protecting the human rights of people with mental disorders and keeping
      them free of restraints can be achieved by providing accessible, community based
      mental health services with continuity of care. China's "686" Program can inform
      similar efforts in low-resource settings where community locking of patients is
      practiced.

PMID- 25848801
TI  - Human Pirh2 is a novel inhibitor of prototype foamy virus replication.
AB  - Prototype foamy virus (PFV) is a member of the unconventional and nonpathogenic
      retroviruses. PFV causes lifelong chronic infections, which are partially
      attributable to a number of host cell factors that restrict viral replication.
      Herein, we identified human p53-induced RING-H2 protein (Pirh2) as a novel
      inhibitor of prototype foamy virus. Overexpression of Pirh2 decreased the
      replication of PFV, whereas knockdown of Pirh2 with specific siRNA increased PFV
      replication. Dual-luciferase assays and coimmunoprecipitation demonstrated that
      Pirh2 negatively influences the Tas-dependent transcriptional activation of the
      PFV long terminal repeat (LTR) and internal promoter (IP) by interacting with the
      transactivator Tas and down-regulating its expression. In addition, the viral
      inhibitory function of Pirh2 is N-terminal and RING domain dependent. Together,
      these results indicated that Pirh2 suppresses PFV replication by negatively
      impacting its transactivator Tas and the transcription of two viral promoters,
      which may contribute to the latency of PFV infection.

PMID- 25848802
TI  - Pulmonary rehabilitation in Canada: A report from the Canadian Thoracic Society
      COPD Clinical Assembly.
AB  - BACKGROUND: Pulmonary rehabilitation (PR) is a recommended intervention in the
      management of individuals with chronic lung disease. It is important to study the
      characteristics and capacity of programs in Canada to confirm best practices and
      identify future areas of program improvement and research. OBJECTIVE: To identify
      all Canadian PR programs, regardless of setting, and to comprehensively describe
      all aspects of PR program delivery. The present article reports the results of
      the survey related to type of program, capacity and program characteristics.
      METHODS: All hospitals in Canada were contacted to identify PR programs. A
      representative from each program completed a 175-item online survey encompassing
      16 domains, 10 of which are reported in the present article. RESULTS: A total of
      155 facilities in Canada offered PR, of which 129 returned surveys (83% response
      rate). PR programs were located in all provinces, but none in the three
      territories. Most (60%) programs were located in hospital settings, 24% were in
      public health units and 8% in recreation centres. The national capacity of
      programs was estimated to be 10,280 patients per year, resulting in 0.4% of all
      Canadians with chronic obstructive pulmonary disease (COPD) and 0.8% of Canadians
      with moderate to severe COPD having access to PR. COPD, interstitial lung
      disease, and asthma were the most common diagnoses of patients. The majority of
      programs had at least four health care professionals involved; 9% had only one
      health care professional involved. CONCLUSION: The present comprehensive survey
      of PR in Canada reports an increase in the number of programs and the total
      number of patients enrolled since the previous survey in 2005. However, PR
      capacity has not kept pace with demand, with only 0.4% of Canadians with COPD
      having access.

PMID- 25848803
TI  - Surgical versus nonsurgical interventions to relieve upper airway obstruction in
      children with Pierre Robin sequence.
AB  - BACKGROUND: Newborns with Pierre Robin sequence (PRS) often experience chronic
      intermittent hypoxemia/hypoventilation associated with airway obstruction. The
      heterogeneity of the severity of upper airway obstruction makes management a
      challenge; the optimal intervention in individual cases is not clear. OBJECTIVE:
      To investigate the prevalence of surgical/nonsurgical interventions for PRS at
      two children's hospitals. Patient characteristics and outcomes were examined.
      METHODS: The present retrospective chart review identified 139 patients with PRS
      born between 2000 and 2010. Demographic information, mode of airway management,
      associated anomalies and syndromes, polysomnography results, length of intensive
      care unit and hospital stay, complications and deaths were extracted. RESULTS:
      Interventions included prone positioning (alone [61%]), tongue-lip adhesion
      (45%), nasopharyngeal intubation (28%), continuous positive airway pressure
      (20%), tracheostomy (19%) and mandibular distraction osteogenesis (5%).
      Tracheostomies were more prevalent in syndromic patients (P=0.03). Patients who
      underwent tracheostomy had a lower birth weight (P=0.03) compared with newborns
      with other interventions. Patients who underwent surgical interventions had
      longer intensive care unit stays (P<0.001). No intervention was associated with a
      statistically significant likelihood of requiring a subsequent intervention.
      Thirty percent of patients underwent polysomnography, with a higher proportion of
      these using continuous positive airway pressure (n=15) (P<0.01). CONCLUSIONS: In
      the present descriptive study, patients with syndromic PRS or low birth weight
      underwent early intervention, which included a tracheostomy. Objective measures
      of airway obstruction were underutilized. Decision making regarding evaluation
      and management of upper airway obstruction in this population remains clinician
      and resource dependent. Reporting data obtained from a large cohort of PRS
      patients is important to compare experiences and motivate future studies
      investigating this complex condition.

PMID- 25848804
TI  - Relationship Between Fatigue and Changes in Swim Technique During an Exhaustive
      Swim Exercise.
AB  - PURPOSE: To analyze the relationship between the responses of isometric peak
      torque (IPT) and maximal rate of force development (RFDmax) with the changes in
      stroking parameters in an exhaustive exercise performed in front crawl. METHODS:
      Fifteen male swimmers performed, on different days, the following protocols:
      maximal 400-m trial, strength tests before and after an exhaustive test at 100%
      of the mean speed obtained during the 400-m test, and the same procedures on day
      2. RESULTS: The IPT of elbow flexors (79.9 +/- 19.4 and 66.7 +/- 20.0 N.m) and
      elbow extensors (95.1 +/- 28.0 N.m and 85.8 +/- 30.5 N.m) was decreased after the
      swim test, as was RFDmax (521.8 +/- 198.6 and 426.0 +/- 229.9 N.m/s; 420.6 +/-
      168.2 and 384.0 +/- 143.5 N.m/s, respectively). Stroke length decreased during
      the swim test (1.96 +/- 0.22 and 1.68 +/- 0.29 m/stroke), while stroke rate
      increased (37.2 +/- 3.14 and 41.3 +/- 4.32 strokes/min). The propulsive phases
      increased while the nonpropulsive phases decreased during the test. Significant
      correlation was found between the changes in IPT and stroke length, stroke rate
      and recovery (elbow flexors), and entry and catch phase (elbow extensors). In
      addition, significant correlation was found between the changes in RFDmax of
      elbow flexors with the changes in pull and recovery phases. CONCLUSION: Changes
      in swim technique during an exhaustive test can be, at least in part, associated
      with fatigue of the arm muscles.

PMID- 25848805
TI  - Different Raman spectral patterns of primary rat pancreatic beta cells and
      insulinoma cells.
AB  - As a noninvasive and label-free analytical technique, Raman spectroscopy has been
      widely used to study the difference between malignant cells and normal cells.
      Insulinomas are functional beta-cell tumors of pancreatic islet cells. They
      exhibit many structural and immunohistochemical features in common with normal
      pancreatic beta cells; thus, they are typically difficult to distinguish under
      the microscope, especially in vivo. We investigated insulinoma and primary rat
      pancreatic beta-cell populations using Raman spectroscopy. The details of the
      optical heterogeneity between these two populations were determined based on
      different Raman regions primarily involving nucleic acid and protein contents,
      which are the most distinct cellular contents in these two types of cells. Using
      principal component analysis-linear discriminant analysis, these two cell types
      can be readily separated. The results of this work indicate that Raman
      spectroscopy is a promising tool for the noninvasive and label-free
      differentiation of insulinoma cells and normal pancreatic beta cells.

PMID- 25848806
TI  - Regeneration of Light-Harvesting Complexes via Dynamic Replacement of
      Photodegraded Chromophores.
AB  - All-synthetic molecular donor-acceptor complexes are designed, which are capable
      of counteracting the effect of photoinduced degradation of donor chromophores.
      Anionic gallium protoporphyrin IX (GaPP) and semiconducting carbon nanotube (CNT)
      are used as a model donor-acceptor complex, which is assembled using DNA
      oligonucleotides. The GaPP-DNA-CNT complex produces an anodic photocurrent in a
      photoelectrochemical cell, which steadily decays due to photo-oxidation. By
      modulating the chemical environment, we showed that the photodegraded
      chromophores may be dissociated from the complex, whereas the DNA-coated carbon
      nanotube acceptors are kept intact. Reassociation with fresh porphyrins leads to
      the full recovery of GaPP absorption and photocurrents. This strategy could form
      a basis for improving the light-harvesting performance of molecular donor
      acceptor complexes and extending their operation lifetime. 

PMID- 25848807
TI  - Lipopolysaccharide perception leads to dynamic alterations in the
      microtranscriptome of Arabidopsis thaliana cells and leaf tissues.
AB  - BACKGROUND: MicroRNAs (miRNAs) are non-coding RNA molecules which have recently
      emerged as important gene regulators in plants and their gene expression analysis
      is becoming increasingly important. miRNAs regulate gene expression at the post
      transcriptional level by translational repression or target degradation of
      specific mRNAs and gene silencing. In order to profile the microtranscriptome of
      Arabidopsis thaliana leaf and callus tissues in response to bacterial
      lipopolysaccharide (LPS), small RNA libraries were constructed at 0 and 3 h post
      induction with LPS and sequenced by Illumina sequencing technology. RESULTS:
      Differential regulation of subset of miRNAs in response to LPS treament was
      observed. Small RNA reads were mapped to the miRNA database and 358 miRNAs
      belonging to 49 miRNA families in the callus tissues and 272 miRNAs belonging to
      40 miRNA families in the leaf tissues were identified. Moreover, target genes for
      all the identified miRNAs families in the leaf tissues and 44 of the 49 miRNAs
      families in the callus tissues were predicted. The sequencing analysis showed
      that in both callus and leaf tissues, various stress regulated-miRNAs were
      differentially expressed and real time PCR validated the expression profile of
      miR156, miR158, miR159, miR169, miR393, miR398, miR399 and miR408 along with
      their target genes. CONCLUSION: A. thaliana callus and leaf callus tissues
      respond to LPS as a microbe-associated molecular pattern molecule through dynamic
      changes to the microtranscriptome associated with differential transcriptional
      regulation in support of immunity and basal resistance.

PMID- 25848808
TI  - Nanowire-bacteria hybrids for unassisted solar carbon dioxide fixation to value
      added chemicals.
AB  - Direct solar-powered production of value-added chemicals from CO2 and H2O, a
      process that mimics natural photosynthesis, is of fundamental and practical
      interest. In natural photosynthesis, CO2 is first reduced to common biochemical
      building blocks using solar energy, which are subsequently used for the synthesis
      of the complex mixture of molecular products that form biomass. Here we report an
      artificial photosynthetic scheme that functions via a similar two-step process by
      developing a biocompatible light-capturing nanowire array that enables a direct
      interface with microbial systems. As a proof of principle, we demonstrate that a
      hybrid semiconductor nanowire-bacteria system can reduce CO2 at neutral pH to a
      wide array of chemical targets, such as fuels, polymers, and complex
      pharmaceutical precursors, using only solar energy input. The high-surface-area
      silicon nanowire array harvests light energy to provide reducing equivalents to
      the anaerobic bacterium, Sporomusa ovata, for the photoelectrochemical production
      of acetic acid under aerobic conditions (21% O2) with low overpotential (eta <
      200 mV), high Faradaic efficiency (up to 90%), and long-term stability (up to 200
      h). The resulting acetate (~6 g/L) can be activated to acetyl coenzyme A (acetyl
      CoA) by genetically engineered Escherichia coli and used as a building block for
      a variety of value-added chemicals, such as n-butanol, polyhydroxybutyrate (PHB)
      polymer, and three different isoprenoid natural products. As such, interfacing
      biocompatible solid-state nanodevices with living systems provides a starting
      point for developing a programmable system of chemical synthesis entirely powered
      by sunlight. 

PMID- 25848809
TI  - Satisfaction with local exercise facility: a rural-urban comparison in China.
AB  - INTRODUCTION: Rural-urban inequalities in China have been widening over the past
      few decades. Compared to their urban counterparts, rural residents may encounter
      various barriers to equal opportunities to effectively engage in physical
      activity. This study examines the rural-urban disparity in physical activity,
      proximity and satisfaction with local exercise facilities. METHODS: An in-person
      survey was conducted in 29 counties of 10 Chinese provinces in 2012. Five
      thousand questionnaires were administered by trained staff with a completion rate
      of 82.1%. The complete sample includes 1661 rural and 2446 urban residents. Eight
      dichotomous outcome measures were used, pertaining to leisure-time physical
      activity engagement; proximity to the nearest exercise facility from home;
      satisfaction level with the quantity, variety, fee levels, opening hours, and
      daily management and services of nearby exercise facilities; and satisfaction
      level with the local public sports service system. Nearest-neighbor matching was
      performed to match rural residents with urban residents by observed individual
      sociodemographics, including gender, age, education level and residential
      province. Pearson's chi2 test was used to assess the difference in
      sociodemographics and outcome measures between rural and urban residents before
      and after matching. RESULTS: Before nearest-neighbor matching, the frequency
      distributions of age and education level are significantly different between
      rural and urban residents (both p<0.0001). After matching, the differences in the
      frequency distributions between rural and urban residents become statistically
      non-significant for all observed sociodemographics: gender (p=0.170), age
      (p=0.934), education level (p=0.244) and residential province (p=1.000). Compared
      to their matched urban counterparts, rural residents are 8.1% (p<0.0001) more
      likely to be physically inactive in their leisure time and 5.8% (p=0.005) less
      likely to live within 30-minute walking distance to the nearest exercise
      facility. Rural residents are 15.7%, 15.7%, 8.6%, 13.5% and 14.7% more likely to
      be unsatisfied with the quantity, variety, fee levels, opening hours, and daily
      management and services of nearby exercise facilities, and 16.1% more likely to
      be unsatisfied with the local public sports service system than matched urban
      residents (all p<0.0001). CONCLUSIONS: Substantial rural-urban disparities tend
      to be present in leisure-time physical activity, proximity to the nearest
      exercise facility, and satisfaction level with exercise facilities and the public
      sports service system. Policy interventions are warranted to improve the
      accessibility and affordability of local exercise facilities in rural areas as a
      way to promote physical activity among Chinese rural residents and reduce
      disparities.

PMID- 25848811
TI  - Transition States and transition state analogue interactions with enzymes.
AB  - Enzymatic transition states have lifetimes of a few femtoseconds (fs).
      Computational analysis of enzyme motions leading to transition state formation
      suggests that local catalytic site motions on the fs time scale provide the
      mechanism to locate transition states. An experimental test of protein fs motion
      and its relation to transition state formation can be provided by isotopically
      heavy proteins. Heavy enzymes have predictable mass-altered bond vibration states
      without altered electrostatic properties, according to the Born-Oppenheimer
      approximation. On-enzyme chemistry is slowed in most heavy proteins, consistent
      with altered protein bond frequencies slowing the search for the transition
      state. In other heavy enzymes, structural changes involved in reactant binding
      and release are also influenced. Slow protein motions associated with substrate
      binding and catalytic site preorganization are essential to allow the subsequent
      fs motions to locate the transition state and to facilitate the efficient release
      of products. In the catalytically competent geometry, local groups move in
      stochastic atomic motion on the fs time scale, within transition state-accessible
      conformations created by slower protein motions. The fs time scale for the
      transition state motions does not permit thermodynamic equilibrium between the
      transition state and stable enzyme states. Isotopically heavy enzymes provide a
      diagnostic tool for fast coupled protein motions to transition state formation
      and mass-dependent conformational changes. The binding of transition state
      analogue inhibitors is the opposite in catalytic time scale to formation of the
      transition state but is related by similar geometries of the enzyme-transition
      state and enzyme-inhibitor interactions. While enzymatic transition states have
      lifetimes as short as 10(-15) s, transition state analogues can bind tightly to
      enzymes with release rates greater than 10(3) s. Tight-binding transition state
      analogues stabilize the rare but evolved enzymatic geometry to form the
      transition state. Evolution to efficient catalysis optimized this geometry and
      its stabilization by a transition state mimic results in tight binding. Release
      rates of transition state analogues are orders of magnitude slower than product
      release in normal catalytic function. During catalysis, product release is
      facilitated by altered chemistry. Compared to the weak associations found in
      Michaelis complexes, transition state analogues involve strong interactions
      related to those in the transition state. Optimum binding of transition state
      analogues occurs when the complex retains the system motions intrinsic to
      transition state formation. Conserved dynamic motion retains the entropic
      components of inhibitor complexes, improving the thermodynamics of analogue
      binding. 

PMID- 25848810
TI  - High-throughput deep sequencing reveals that microRNAs play important roles in
      salt tolerance of euhalophyte Salicornia europaea.
AB  - BACKGROUND: microRNAs (miRNAs) are implicated in plant development processes and
      play pivotal roles in plant adaptation to environmental stresses. Salicornia
      europaea, a salt mash euhalophyte, is a suitable model plant to study salt
      adaptation mechanisms. S. europaea is also a vegetable, forage, and oilseed that
      can be used for saline land reclamation and biofuel precursor production on
      marginal lands. Despite its importance, no miRNA has been identified from S.
      europaea thus far. RESULTS: Deep sequencing was performed to investigate small
      RNA transcriptome of S. europaea. Two hundred and ten conserved miRNAs comprising
      51 families and 31 novel miRNAs (including seven miRNA star sequences) belonging
      to 30 families were identified. About half (13 out of 31) of the novel miRNAs
      were only detected in salt-treated samples. The expression of 43 conserved and 13
      novel miRNAs significantly changed in response to salinity. In addition, 53
      conserved and 13 novel miRNAs were differentially expressed between the shoots
      and roots. Furthermore, 306 and 195 S. europaea unigenes were predicted to be
      targets of 41 conserved and 29 novel miRNA families, respectively. These targets
      encoded a wide range of proteins, and genes involved in transcription regulation
      constituted the largest category. Four of these genes encoding laccase, F-box
      family protein, SAC3/GANP family protein, and NADPH cytochrome P-450 reductase
      were validated using 5'-RACE. CONCLUSIONS: Our results indicate that specific
      miRNAs are tightly regulated by salinity in the shoots and/or roots of S.
      europaea, which may play important roles in salt tolerance of this euhalophyte.
      The S. europaea salt-responsive miRNAs and miRNAs that target transcription
      factors, nucleotide binding site-leucine-rich repeat proteins and enzymes
      involved in lignin biosynthesis as well as carbon and nitrogen metabolism may be
      applied in genetic engineering of crops with high stress tolerance, and genetic
      modification of biofuel crops with high biomass and regulatable lignin
      biosynthesis.

PMID- 25848812
TI  - Towards a physically more active lifestyle based on one's own values: the results
      of a randomized controlled trial among physically inactive adults.
AB  - BACKGROUND: The high prevalence of physical inactivity has led to a search for
      novel and feasible interventions that will enhance physical activity, especially
      among the least physically active individuals. This randomized controlled trial
      aimed to determine the effectiveness of a value-based intervention to promote a
      physically more active lifestyle among physically inactive adults. The framework
      of the study was based on Acceptance and Commitment Therapy (ACT). METHODS:
      Physically inactive participants aged 30 to 50 years (n = 138) were randomly
      allocated to a feedback (FB, n = 69) or an acceptance- and commitment-based group
      (ACT + FB, n = 69). Both groups received written feedback about their objectively
      measured physical activity and were offered a body composition analysis. In
      addition, the participants in the ACT + FB group attended six group sessions and
      were given a pedometer for self-monitoring their physical activity during the
      nine-week intervention. The primary outcome was physical activity. In addition,
      participants' cognitions related to exercise and physical activity were evaluated
      at baseline and at three- and six-month follow-ups. The changes in mean physical
      activity level were analysed using multilevel random regression and rank order
      stability, using the structural equation model. RESULTS: Participants in both
      groups increased their objectively measured and self-reported physical activity
      with high individual differences. No difference was observed in the change of
      physical activity level between the FB and ACT + FB groups over time. However,
      the cognitions related to physical activity and exercise improved more in the ACT
      + FB group than in the FB group. In addition, after re-analyzing the data among
      the non-depressive participants, higher stability was observed in objectively
      measured physical activity at the individual level between the three- and six
      month follow-ups in the ACT + FB group as compared to FB group. CONCLUSIONS:
      Acceptance- and commitment-based group intervention, combined with the self
      monitoring of physical activity, was beneficial in supporting the cognition
      related to exercise and physical activity, and brought more stability to the
      individual level physical activity behaviour change, especially among the non
      depressive participants. TRIAL REGISTRATION: ClinicalTrials.gov, number
      NCT01796990. Registered in February 2013.

PMID- 25848813
TI  - Population structure and genetic diversity characterization of a sunflower
      association mapping population using SSR and SNP markers.
AB  - BACKGROUND: Argentina has a long tradition of sunflower breeding, and its
      germplasm is a valuable genetic resource worldwide. However, knowledge of the
      genetic constitution and variability levels of the Argentinean germplasm is still
      scarce, rendering the global map of cultivated sunflower diversity incomplete. In
      this study, 42 microsatellite loci and 384 single nucleotide polymorphisms (SNPs)
      were used to characterize the first association mapping population used for
      quantitative trait loci mapping in sunflower, along with a selection of allied
      open-pollinated and composite populations from the germplasm bank of the National
      Institute of Agricultural Technology of Argentina. The ability of different kinds
      of markers to assess genetic diversity and population structure was also
      evaluated. RESULTS: The analysis of polymorphism in the set of sunflower
      accessions studied here showed that both the microsatellites and SNP markers were
      informative for germplasm characterization, although to different extents. In
      general, the estimates of genetic variability were moderate. The average genetic
      diversity, as quantified by the expected heterozygosity, was 0.52 for SSR loci
      and 0.29 for SNPs. Within SSR markers, those derived from non-coding regions were
      able to capture higher levels of diversity than EST-SSR. A significant
      correlation was found between SSR and SNP- based genetic distances among
      accessions. Bayesian and multivariate methods were used to infer population
      structure. Evidence for the existence of three different genetic groups was found
      consistently across data sets (i.e., SSR, SNP and SSR + SNP), with the
      maintainer/restorer status being the most prevalent characteristic associated
      with group delimitation. CONCLUSION: The present study constitutes the first
      report comparing the performance of SSR and SNP markers for population genetics
      analysis in cultivated sunflower. We show that the SSR and SNP panels examined
      here, either used separately or in conjunction, allowed consistent estimations of
      genetic diversity and population structure in sunflower breeding materials. The
      generated knowledge about the levels of diversity and population structure of
      sunflower germplasm is an important contribution to this crop breeding and
      conservation.

PMID- 25848814
TI  - Rationally Designed MicroRNA-Based Genetic Classifiers Target Specific Neurons in
      the Brain.
AB  - Targeting transgene expression to specific cell types in vivo has proven
      instrumental in characterizing the functional role of defined cell populations.
      Genetic classifiers, synthetic transgene constructs designed to restrict
      expression to particular classes of cells, commonly rely on transcriptional
      promoters to define cellular specificity. However, the large size of many natural
      promoters complicates their use in viral vectors, an important mode of transgene
      delivery in the brain and in human gene therapy. Here, we expanded upon an
      emerging classifier platform, orthogonal to promoter-based strategies, that
      exploits endogenous microRNA regulation to target gene expression. Such
      classifiers have been extensively explored in other tissues; however, their use
      in the nervous system has thus far been limited to targeting gene expression
      between neurons and supporting cells. Here, we tested the possibility of using
      combinatory microRNA regulation to specify gene targeting between neuronal
      subtypes, and successfully targeted inhibitory cells in the neocortex. These
      classifiers demonstrate the feasibility of designing a new generation of microRNA
      based neuron-type- and brain-region-specific gene expression targeting
      neurotechnologies. 

PMID- 25848816
TI  - Erratum to: "A novel role for ezrin in breast cancer angio/lymphangiogenesis".

PMID- 25848815
TI  - Inhibition of HMGCoA reductase by simvastatin protects mice from injurious
      mechanical ventilation.
AB  - BACKGROUND: Mortality from severe acute respiratory distress syndrome exceeds 40%
      and there is no available pharmacologic treatment. Mechanical ventilation
      contributes to lung dysfunction and mortality by causing ventilator-induced lung
      injury. We explored the utility of simvastatin in a mouse model of severe
      ventilator-induced lung injury. METHODS: Male C57BL6 mice (n = 7/group) were
      pretreated with simvastatin or saline and received protective (8 mL/kg) or
      injurious (25 mL/kg) ventilation for four hours. Three doses of simvastatin (20
      mg/kg) or saline were injected intraperitoneally on days -2, -1 and 0 of the
      experiment. Lung mechanics, (respiratory system elastance, tissue damping and
      airway resistance), were evaluated by forced oscillation technique, while
      respiratory system compliance was measured with quasi-static pressure-volume
      curves. A pathologist blinded to treatment allocation scored hematoxylin-eosin
      stained lung sections for the presence of lung injury. Pulmonary endothelial
      dysfunction was ascertained by bronchoalveolar lavage protein content and lung
      tissue expression of endothelial junctional protein Vascular Endothelial cadherin
      by immunoblotting. To assess the inflammatory response in the lung, we determined
      bronchoalveolar lavage fluid total cell content and neutrophil fraction by
      microscopy and staining in addition to Matrix-Metalloprotease-9 by ELISA. For the
      systemic response, we obtained plasma levels of Tumor Necrosis Factor-alpha,
      Interleukin-6 and Matrix-Metalloprotease-9 by ELISA. Statistical hypothesis
      testing was undertaken using one-way analysis of variance and Tukey's post hoc
      tests. RESULTS: Ventilation with high tidal volume (HVt) resulted in
      significantly increased lung elastance by 3-fold and decreased lung compliance by
      45% compared to low tidal volume (LVt) but simvastatin abrogated lung mechanical
      alterations of HVt. Histologic lung injury score increased four-fold by HVt but
      not in simvastatin-pretreated mice. Lavage pleocytosis and neutrophilia were
      induced by HVt but were significantly attenuated by simvastatin. Microvascular
      protein permeability increase 20-fold by injurious ventilation but only 4-fold
      with simvastatin. There was a 3-fold increase in plasma Tumor Necrosis Factor
      alpha, a 7-fold increase in plasma Interleukin-6 and a 20-fold increase in lavage
      fluid Matrix-Metalloprotease-9 by HVt but simvastatin reduced these levels to
      control. Lung tissue vascular endothelial cadherin expression was significantly
      reduced by injurious ventilation but remained preserved by simvastatin.
      CONCLUSION: High-dose simvastatin prevents experimental hyperinflation lung
      injury by angioprotective and anti-inflammatory effects.

PMID- 25848819
TI  - Electronic pseudogap-driven formation of new double-perovskite-like borides
      within the Sc2Ir6-xTxB (T = Pd, Ni; x = 0-6) series.
AB  - Analysis of the electronic density of states of the hypothetical ternary double
      perovskite-like phases "Sc2T6B (T = Ir, Pd, Ni)" reveals the presence of deep and
      large pseudogaps between 61 and 68 valence electrons (VE) as well as a strong
      peak at 69 VEs. Subsequently, crystal orbital Hamilton population (COHP) bonding
      analysis shows that the heteroatomic T-B and Sc-T interactions are optimized in
      Sc2Ir6B (63 VE) but not in "Sc2Pd6B (69 VE)" and "Sc2Ni6B (69 VE)", thus
      indicating less stability for these VE-richer phases. These findings point out
      the possibility of discovering new double-perovskite-like borides through
      chemical substitution and lead to the study of the Sc2Ir6-xPdxB and Sc2Ir6-xNixB
      (x = 0-6; VE = 63-69) series, for which powder samples and single crystals were
      synthesized by arc melting the elements. Superstructure reflections were observed
      in the powder diffractograms of Sc2Ir6-xPdxB and Sc2Ir6-xNixB for x = 0-5 and VE
      = 63-68, thereby showing that these phases crystallize in the double-perovskite
      like Ti2Rh6B-type structure (space group Fm3m, Z = 4). Single-crystal and
      Rietveld refinement results confirm and extend these findings because Pd (or Ni)
      is found to mix exclusively with Ir in all quaternary compositions. For x = 6, no
      superstructure reflections were observed, in accordance with the theoretical
      expectation for the 69 VE phases. 

PMID- 25848818
TI  - The contrasting N management of two oilseed rape genotypes reveals the mechanisms
      of proteolysis associated with leaf N remobilization and the respective
      contributions of leaves and stems to N storage and remobilization during seed
      filling.
AB  - BACKGROUND: Oilseed rape is the third largest oleaginous crop in the world but
      requires high levels of N fertilizer of which only 50% is recovered in seeds.
      This weak N use efficiency is associated with a low foliar N remobilization,
      leading to a significant return of N to the soil and a risk of pollution.
      Contrary to what is observed during senescence in the vegetative stages, N
      remobilization from stems and leaves is considered efficient during monocarpic
      senescence. However, the contribution of stems towards N management and the
      cellular mechanisms involved in foliar remobilization remain largely unknown. To
      reach this goal, the N fluxes at the whole plant level from bolting to mature
      seeds and the processes involved in leaf N remobilization and proteolysis were
      investigated in two contrasting genotypes (Aviso and Oase) cultivated under ample
      or restricted nitrate supply. RESULTS: During seed filling in both N conditions,
      Oase efficiently allocated the N from uptake to seeds while Aviso favoured a
      better N remobilization from stems and leaves towards seeds. Nitrate restriction
      decreased seed yield and oil quality for both genotypes but Aviso had the best
      seed N filling. Under N limitation, Aviso had a better N remobilization from
      leaves to stems before the onset of seed filling. Afterwards, the higher N
      remobilization from stems and leaves of Aviso led to a higher final N amount in
      seeds. This high leaf N remobilization is associated with a better
      degradation/export of insoluble proteins, oligopeptides, nitrate and/or ammonia.
      By using an original method based on the determination of Rubisco degradation in
      the presence of inhibitors of proteases, efficient proteolysis associated with
      cysteine proteases and proteasome activities was identified as the mechanism of N
      remobilization. CONCLUSION: The results confirm the importance of foliar N
      remobilization after bolting to satisfy seed filling and highlight that an
      efficient proteolysis is mainly associated with (i) cysteine proteases and
      proteasome activities and (ii) a fine coordination between proteolysis and export
      mechanisms. In addition, the stem may act as transient storage organs in the case
      of an asynchronism between leaf N remobilization and N demand for seed filling.

PMID- 25848817
TI  - Poorly controlled type 2 diabetes is accompanied by significant morphological and
      ultrastructural changes in both erythrocytes and in thrombin-generated fibrin:
      implications for diagnostics.
AB  - We have noted in previous work, in a variety of inflammatory diseases, where iron
      dysregulation occurs, a strong tendency for erythrocytes to lose their normal
      discoid shape and to adopt a skewed morphology (as judged by their axial ratios
      in the light microscope and by their ultrastructure in the SEM). Similarly, the
      polymerization of fibrinogen, as induced in vitro by added thrombin, leads not to
      the common 'spaghetti-like' structures but to dense matted deposits. Type 2
      diabetes is a known inflammatory disease. In the present work, we found that the
      axial ratio of the erythrocytes of poorly controlled (as suggested by increased
      HbA1c levels) type 2 diabetics was significantly increased, and that their fibrin
      morphologies were again highly aberrant. As judged by scanning electron
      microscopy and in the atomic force microscope, these could be reversed, to some
      degree, by the addition of the iron chelators deferoxamine (DFO) or deferasirox
      (DFX). As well as their demonstrated diagnostic significance, these morphological
      indicators may have prognostic value. 

PMID- 25848820
TI  - Prognostic stromal gene signatures in breast cancer.
AB  - INTRODUCTION: Global gene expression analysis of tumor samples has been a
      valuable tool to subgroup tumors and has the potential to be of prognostic and
      predictive value. However, tumors are heterogeneous, and homogenates will consist
      of several different cell types. This study was designed to obtain more refined
      expression data representing different compartments of the tumor. METHODS:
      Formalin-fixed paraffin-embedded stroma-rich triple-negative breast cancer tumors
      were laser-microdissected, and RNA was extracted and processed to enable
      microarray hybridization. Genes enriched in stroma were identified and used to
      generate signatures by identifying correlating genes in publicly available data
      sets. The prognostic implications of the signature were analyzed. RESULTS:
      Comparison of the expression pattern from stromal and cancer cell compartments
      from three tumors revealed a number of genes that were essentially specifically
      expressed in the respective compartments. The stroma-specific genes indicated
      contribution from fibroblasts, endothelial cells, and immune/inflammatory cells.
      The gene set was expanded by identifying correlating mRNAs using breast cancer
      mRNA expression data from The Cancer Genome Atlas. By iterative analyses, 16 gene
      signatures of highly correlating genes were characterized. Based on the gene
      composition, they seem to represent different cell types. In multivariate Cox
      proportional hazard models, two immune/inflammatory signatures had opposing
      hazard ratios for breast cancer recurrence also after adjusting for
      clinicopathological variables and molecular subgroup. The signature associated
      with poor prognosis consisted mainly of C1Q genes and the one associated with
      good prognosis contained HLA genes. This association with prognosis was seen for
      other cancers as well as in other breast cancer data sets. CONCLUSIONS: Our data
      indicate that the molecular composition of the immune response in a tumor may be
      a powerful predictor of cancer prognosis.

PMID- 25848821
TI  - Ni-Catalyzed C-H Functionalization in the Formation of a Complex Heterocycle:
      Synthesis of the Potent JAK2 Inhibitor BMS-911543.
AB  - BMS-911543 is a complex pyrrolopyridine investigated as a potential treatment for
      myeloproliferative disorders. The development of a short and efficient synthesis
      of this molecule is described. During the course of our studies, a Ni-mediated C
      N bond formation was invented, which enabled the rapid construction of the highly
      substituted 2-aminopyridine core. The synthesis of this complex, nitrogen-rich
      heterocycle was accomplished in only eight steps starting from readily available
      materials. 

PMID- 25848823
TI  - N-Heterocyclic Carbene-Catalyzed Ring Opening Polymerization of epsilon
      Caprolactone with and without Alcohol Initiators: Insights from Theory and
      Experiment.
AB  - Computational investigations with density functional theory (DFT) have been
      performed on the N-heterocyclic carbene (NHC) catalyzed ring-opening
      polymerization of epsilon-caprolactone in the presence and in the absence of a
      methanol initiator. Much like the zwitterionic ring opening (ZROP) of delta
      valerolactone which was previously reported, calculations predict that the
      mechanism of the ZROP of caprolactone that occurs without an alcohol present
      involves a high-barrier step involving ring opening of the zwitterionic
      tetrahedral intermediate formed after the initial nucleophilic attack of NHC on
      caprolactone. However, the operative mechanism by which caprolactone is
      polymerized in the presence of an alcohol initiator does not involve the
      analogous mechanism involving initial nucleophilic attack by the organocatalytic
      NHC. Instead, the NHC activates the alcohol through hydrogen bonding and promotes
      nucleophilic attack and the subsequent ring-opening steps that occur during
      polymerization. The largest free energy barrier for the hydrogen-bonding
      mechanism in alcohol involves nucleophilic attack, while that for both ZROP
      processes involves ring opening of the initially formed zwitterionic tetrahedral
      intermediate. The DFT calculations predict that the rate of polymerization in the
      presence of alcohol is faster than the reaction performed without an alcohol
      initiator; this prediction has been validated by experimental kinetic studies. 

PMID- 25848822
TI  - A "Smart" 128Xe NMR Biosensor for pH-Dependent Cell Labeling.
AB  - Here we present a "smart" xenon-129 NMR biosensor that undergoes a peptide
      conformational change and labels cells in acidic environments. To a cryptophane
      host molecule with high Xe affinity, we conjugated a 30mer EALA-repeat peptide
      that is alpha-helical at pH 5.5 and disordered at pH 7.5. The (129)Xe NMR
      chemical shift at room temperature was strongly pH-dependent (Deltadelta = 3.4
      ppm): delta = 64.2 ppm at pH 7.5 vs delta = 67.6 ppm at pH 5.5, where
      Trp(peptide)-cryptophane interactions were evidenced by Trp fluorescence
      quenching. Using hyper-CEST NMR, we probed peptidocryptophane detection limits at
      low-picomolar (10(-11) M) concentration, which compares favorably to other NMR pH
      reporters at 10(-2)-10(-3) M. Finally, in biosensor-HeLa cell solutions, peptide
      cell membrane insertion at pH 5.5 generated a 13.4 ppm downfield cryptophane
      (129)Xe NMR chemical shift relative to pH 7.5 studies. This highlights new uses
      for (129)Xe as an ultrasensitive probe of peptide structure and function, along
      with potential applications for pH-dependent cell labeling in cancer diagnosis
      and treatment. 

PMID- 25848825
TI  - Emergent and after hours calls in skilled care facilities.

PMID- 25848824
TI  - Fracture prevention in COPD patients; a clinical 5-step approach.
AB  - Although osteoporosis and its related fractures are common in patients with COPD,
      patients at high risk of fracture are poorly identified, and consequently,
      undertreated. Since there are no fracture prevention guidelines available that
      focus on COPD patients, we developed a clinical approach to improve the
      identification and treatment of COPD patients at high risk of fracture. We
      organised a round-table discussion with 8 clinical experts in the field of COPD
      and fracture prevention in the Netherlands in December 2013. The clinical experts
      presented a review of the literature on COPD, osteoporosis and fracture
      prevention. Based on the Dutch fracture prevention guideline, they developed a 5
      step clinical approach for fracture prevention in COPD. Thereby, they took into
      account both classical risk factors for fracture (low body mass index, older age,
      personal and family history of fracture, immobility, smoking, alcohol intake, use
      of glucocorticoids and increased fall risk) and COPD-specific risk factors for
      fracture (severe airflow obstruction, pulmonary exacerbations and oxygen
      therapy). Severe COPD (defined as postbronchodilator FEV1 < 50% predicted) was
      added as COPD-specific risk factor to the list of classical risk factors for
      fracture. The 5-step clinical approach starts with case finding using clinical
      risk factors, followed by risk evaluation (dual energy X-ray absorptiometry and
      imaging of the spine), differential diagnosis, treatment and follow-up. This
      systematic clinical approach, which is evidence-based and easy-to-use in daily
      practice by pulmonologists, should contribute to optimise fracture prevention in
      COPD patients at high risk of fracture.

PMID- 25848826
TI  - Update on managing generalized anxiety disorder in older adults.
AB  - With the recent updates to the Diagnostic and Statistical Manual of Mental
      Disorders (5th edition; DSM-5), there are many questions on how to care for older
      adults with generalized anxiety disorder (GAD) and other psychiatric conditions.
      The current article reviews the new changes to the DSM-5 for diagnosis of GAD,
      discusses new anxiety assessment scales that are validated in older adults,
      evaluates pharmacological agents that have been studied in older adults for GAD
      treatment, and provides monitoring recommendations to help those who provide care
      to older adults experiencing GAD.

PMID- 25848827
TI  - Barriers to better care.

PMID- 25848829
TI  - De novo transcriptome sequencing to identify the sex-determination genes in
      Hyriopsis schlegelii.
AB  - This study presents the first analysis of expressed transcripts in the spermary
      and ovary of Hyriopsis schlegelii (H. schlegelii). A total of 132,055 unigenes
      were obtained and 31,781 of these genes were annotated. In addition, 19,511
      upregulated and 25,911 downregulated unigenes were identified in the spermary.
      Ten sex-determination genes were selected and further analyzed by real-time PCR.
      In addition, mammalian genes reported to govern sex-determination pathways,
      including Sry, Dmrt1, Dmrt2, Sox9, GATA4, and WT1 in males and Wnt4, Rspo1,
      Foxl2, and beta-catenin in females, were also identified in H. schlegelii. These
      results suggest that H. schlegelii and mammals use similar gene regulatory
      mechanisms to control sex determination. Moreover, genes associated with dosage
      compensation mechanisms, such as Msl1, Msl2, and Msl3, and hermaphrodite
      phenotypes, such as Tra-1, Tra-2alpha, Tra-2beta, Fem1A, Fem1B, and Fem1C, were
      also identified in H. schlegelii. The identification of these genes indicates
      that diverse regulatory mechanisms regulate sexual polymorphism in H. schlegelii.

PMID- 25848828
TI  - Antibody-based screening of cell wall matrix glycans in ferns reveals taxon,
      tissue and cell-type specific distribution patterns.
AB  - BACKGROUND: While it is kno3wn that complex tissues with specialized functions
      emerged during land plant evolution, it is not clear how cell wall polymers and
      their structural variants are associated with specific tissues or cell types.
      Moreover, due to the economic importance of many flowering plants, ferns have
      been largely neglected in cell wall comparative studies. RESULTS: To explore fern
      cell wall diversity sets of monoclonal antibodies directed to matrix glycans of
      angiosperm cell walls have been used in glycan microarray and in situ analyses
      with 76 fern species and four species of lycophytes. All major matrix glycans
      were present as indicated by epitope detection with some variations in abundance.
      Pectic HG epitopes were of low abundance in lycophytes and the CCRC-M1
      fucosylated xyloglucan epitope was largely absent from the Aspleniaceae. The LM15
      XXXG epitope was detected widely across the ferns and specifically associated
      with phloem cell walls and similarly the LM11 xylan epitope was associated with
      xylem cell walls. The LM5 galactan and LM6 arabinan epitopes, linked to pectic
      supramolecules in angiosperms, were associated with vascular structures with only
      limited detection in ground tissues. Mannan epitopes were found to be associated
      with the development of mechanical tissues. We provided the first evidence for
      the presence of MLG in leptosporangiate ferns. CONCLUSIONS: The data sets
      indicate that cell wall diversity in land plants is multifaceted and that matrix
      glycan epitopes display complex spatio-temporal and phylogenetic distribution
      patterns that are likely to relate to the evolution of land plant body plans.

PMID- 25848830
TI  - Single-Crystalline Aluminum Nanostructures on a Semiconducting GaAs Substrate for
      Ultraviolet to Near-Infrared Plasmonics.
AB  - Aluminum, as a metallic material for plasmonics, is of great interest because it
      extends the applications of surface plasmon resonance into the ultraviolet (UV)
      region and is superior to noble metals in natural abundance, cost, and
      compatibility with modern semiconductor fabrication processes. Ultrasmooth single
      crystalline metallic films are beneficial for the fabrication of high-definition
      plasmonic nanostructures, especially complex integrated nanocircuits. The absence
      of surface corrugation and crystal boundaries also guarantees superior optical
      properties and applications in nanolasers. Here, we present UV to near-infrared
      plasmonic resonance of single-crystalline aluminum nanoslits and nanoholes. The
      high-definition nanostructures are fabricated with focused ion-beam milling into
      an ultrasmooth single-crystalline aluminum film grown on a semiconducting GaAs
      substrate with a molecular beam epitaxy method. The single-crystalline aluminum
      film shows improved reflectivity and reduced two-photon photoluminescence (TPPL)
      due to the ultrasmooth surface. Both linear scattering and nonlinear TPPL are
      studied in detail. The nanoslit arrays show clear Fano-like resonance, and the
      nanoholes are found to support both photonic modes and localized surface plasmon
      resonance. We also found that TPPL generation is more efficient when the
      excitation polarization is parallel rather than perpendicular to the edge of the
      aluminum film. Such a counterintuitive phenomenon is attributed to the high
      refractive index of the GaAs substrate. We show that the polarization of TPPL
      from aluminum preserves the excitation polarization and is independent of the
      crystal orientation of the film or substrate. Our study gains insight into the
      optical property of aluminum nanostructures on a high-index semiconducting GaAs
      substrate and illustrates a practical route to implement plasmonic devices onto
      semiconductors for future hybrid nanodevices. 

PMID- 25848831
TI  - A single nucleotide polymorphism in the MTOR gene is associated with recurrent
      spontaneous abortion in the Chinese female population.
AB  - Recurrent spontaneous abortion (RSA) is a multi-factor disease. The mammalian
      target of the the rapamycin (MTOR) gene has been reported to be involved in mouse
      embryo development and regulates the proliferation of embryonic stem cells. Our
      study explored the relationship between the single nucleotide polymorphism (SNP)
      rs17027478 in the promoter region of MTOR gene and the development of RSA. A
      total of 306 patients with RSA and 127 healthy females as the controls were
      recruited in the case-control study. The predesigned TaqMan SNP Genotyping Assay
      was adopted to analyze the association between rs17027478 and the development of
      RSA. Quantitative real-time reverse transcription polymerase chain reaction and
      luciferase reporter assays were conducted to analyze the function of the variant.
      It was found that a significant association exists between the variant and the
      risk of RSA among the patients who experienced no less than three spontaneous
      abortions (p = 0.043). However, the significant difference disappeared among the
      total samples (p = 0.524). Furthermore, we observed lower MTOR mRNA levels in the
      blood of RSA patients compared with healthy females (p = 0.020). The luciferase
      reporter assay showed that the rs17027478A allele significantly reduced the
      luciferase activity (p = 0.029). The results demonstrated that the variant
      rs17027478 in the promoter region of MTOR might be a good candidate responsible
      for the pathogenesis of RSA. Abbreviations RSA recurrent spontaneous abortion
      MTOR mammalian target of rapamycin SNP single nucleotide polymorphism qRT-PCR
      quantitative real-time polymerase chain reaction URSA unexplained recurrent
      spontaneous abortion mTORC1 mTOR complex 1 ESC embryonic stem cells HKE-293 human
      embryonic kidney 293 cells HWE Hardy-Weinberg equilibrium ANOVA one-way analysis
      of variance. 

PMID- 25848833
TI  - Polylactide/Poly(omega-hydroxytetradecanoic acid) Reactive Blending: A Green
      Renewable Approach to Improving Polylactide Properties.
AB  - A green manufacturing technique, reactive extrusion (REx), was employed to
      improve the mechanical properties of polylactide (PLA). To achieve this goal, a
      fully biosourced PLA based polymer blend was conceived by incorporating small
      quantities of poly(omega-hydroxytetradecanoic acid) (PC14). PLA/PC14 blends were
      compatibilized by transesterification reactions promoted by 200 ppm titanium
      tetrabutoxide (Ti(OBu)4) during REx. REx for 15 min at 150 rpm and 200  degrees C
      resulted in enhanced blend mechanical properties while minimizing losses in PLA
      molecular weight. SEM analysis of the resulting compatibilized phase-separated
      blends showed good adhesion between dispersed PC14 phases within the continuous
      PLA phase. Direct evidence for in situ synthesis of PLA-b-PC14 copolymers was
      obtained by HMBC and HSQC NMR experiments. The size of the dispersed phase was
      tuned by the screw speed to "tailor" the blend morphology. In the presence of 200
      ppm Ti(OBu)4, inclusion of only 5% PC14 increased the elongation at break of PLA
      from 3 to 140% with only a slight decrease in the tensile modulus (3200 to 2900
      MPa). Furthermore, PLA's impact strength was increased by 2.4* that of neat PLA
      for 20% PC14 blends prepared by REx. Blends of PLA and PC14 are expected to
      expand the potential uses of PLA-based materials. 

PMID- 25848832
TI  - Heroin activates ATF3 and CytC via c-Jun N-terminal kinase pathways to mediate
      neuronal apoptosis.
AB  - BACKGROUND Drug abuse and addiction has become a major public health problem that
      impacts all societies. The use of heroin may cause spongiform leukoencephalopathy
      (SLE). MATERIAL AND METHODS Cerebellar granule cells were derived from 7-day-old
      Sprague-Dawley rat pups. Neurons were dissociated from freshly dissected
      cerebella by mechanical disruption in the presence of 0.125% trypsin and DNaseI
      and then seeded at a density of 4*10^6 cells/ml in Dulbecco's modified Eagle's
      medium/nutrient mixture F-12 ham's containing 10% fetal bovine serum and Arc
      C(sigma) at concentrations to inhibit glial cell growth inoculated into 6-well
      plates and a small dish. RESULTS We found that heroin induces the apoptosis of
      primary cultured cerebellar granule cells (CGCS) and that the c-Jun N-terminal
      kinase (JNK) pathway was activated under heroin treatment and stimulated obvious
      increases in the levels of C-jun, Cytc, and ATF3mRNA. CYTC and ATF3 were
      identified as candidate targets of the JNK/c-Jun pathway in this process because
      the specificity inhibitors SP600125 of JNK/C-jun pathways reduced the levels of C
      jun, Cytc, and ATF3mRNA. The results suggested that SP600125 of JNK/C-jun can
      inhibit heroin-induced apoptosis of neurons. CONCLUSIONS The present study
      analyzes our understanding of the critical role of the JNK pathway in the process
      of neuronal apoptosis induced by heroin, and suggests a new and effective
      strategy to treat SLE. 

PMID- 25848834
TI  - Synthesis of Strong Light Scattering Absorber of TiO2-CMK-3/Ag for Photocatalytic
      Water Splitting under Visible Light Irradiation.
AB  - The enhanced water splitting photocurrent has been observed through plasmonic
      mesoporous composite electrode TiO2-CMK-3/Ag under visible light irradiation.
      Strong light absorption achieved from the integrations of ordered mesoporous
      carbon (CMK-3) and silver plasmonic nanoparticles (NPs) layer in the TiO2, which
      significantly increased the effective optical depth of TiO2-CMK-3/Ag
      photoelectrode. The carbon-based CMK-3 also increased the surface wetting
      behavior and conductivity of the photoelectrodes, which resulted in a higher ion
      exchange rate and faster electron transport. The synthesis of high crystalline
      TiO2-CMK-3/Ag composite photocatalyst was verified by X-ray diffraction (XRD) and
      scanning electron microscopy (SEM). Pronounced enhancement of light absorption of
      TiO2-CMK-3/Ag photoelectrode was confirmed by UV/vis spectrophotometers. Two
      orders of magnitude of the enhanced water splitting photocurrent were obtained in
      the TiO2-CMK-3/Ag composite photoelectrode with respect to TiO2 only. Finally,
      spatially resolved mapping photocurrents were also demonstrated in this study. 

PMID- 25848835
TI  - Potential ecological roles of flavonoids from Stellera chamaejasme.
AB  - Stellera chamaejasme L. (Thymelaeaceae), a perennial weed, distributes widely in
      the grasslands of Russia, Mongolia and China. The plant synthesizes various
      secondary metabolites including a group of flavonoids. To our knowledge,
      flavonoids play important roles in the interactions between plants and the
      environment. So, what are the benefits to S. chamaejasme from producing these
      flavonoids? Here, we discuss the potential ecological role of flavonoids from S.
      chamaejasme in protecting the plant from insects and other herbivores, as well as
      pathogens and competing plant species, and new data are provided on the
      phytotoxicity of flavonoids from S. chamaejasme toward Poa annua L. 

PMID- 25848836
TI  - Feasibility of Using Phytoextraction to Remediate a Compost-Based Soil
      Contaminated with Cadmium.
AB  - Greenhouse and in-situ field experiments were used to determine the potential for
      phytoextraction to remediate soil contaminated with Cd from municipal solid waste
      (MSW) and sewage sludge (SS) compost application at a Peterborough (Canada) site.
      For the greenhouse experiment, one native (Chenopodium album) and three
      naturalized (Poa compressa, Brassica juncea, Helianthus annuus) plant species
      were planted in soil containing no detectable Cd (<1.0 MUg.g(-1)), and soil from
      the site containing low (5.0 +/- 0.3 MUg.g(-1) Cd), and high (16.5 +/- 1.2 MUg?g(
      1) Cd) Cd concentrations. Plant uptake was low (root BAFs <=0.5) for all species
      except P. compressa in the low Cd treatment (BAF 1.0). Only B. juncea accumulated
      Cd in its shoots, though uptake was low (BAF <=0.3). For the field experiment, B.
      juncea was planted in-situ in areas of low and high Cd concentrations. Brassica
      juncea Cd uptake was low (root and shoot BAFs <0.2) in both treatments.
      Sequential extraction analysis indicated that Cd is retained primarily by low
      bioavailability soil fractions, and phytoextraction is therefore not feasible at
      this site. Though low Cd bioavailability has negative implications for Cd
      phytoextraction from MSW/SS compost-based soils, it may limit receptor exposure
      to Cd sufficiently to eliminate the potential for risk at this site.

PMID- 25848838
TI  - Perceptions of a good death among German medical students.
AB  - The purpose of our study was to examine the perceptions of a good death among
      medical students, who are future care providers. The authors identified 9 domains
      that contribute to a good death according to first- and fifth-year medical
      students (N=432). From their perspective, being free from pain and physical
      distress is only 1 important component of a good death, and other elements such
      as psychosocial issues should also be taken into account. A majority of medical
      students considers psychosocial well-being as a highly relevant aspect of
      patients' conditions. The results of this study could help to develop concepts
      for better care and more empathy, which are needed to ensure a good death for all
      patients.

PMID- 25848837
TI  - Proteomic and metabolomic analyses provide insight into production of volatile
      and non-volatile flavor components in mandarin hybrid fruit.
AB  - BACKGROUND: Although many of the volatile constituents of flavor and aroma in
      citrus have been identified, the knowledge of molecular mechanisms and regulation
      of volatile production are very limited. Our aim was to understand mechanisms of
      flavor volatile production and regulation in mandarin fruit. RESULT: Fruits of
      two mandarin hybrids, Temple and Murcott with contrasting volatile and non-
      volatile profiles, were collected at three developmental stages. A combination of
      methods, including the isobaric tags for relative and absolute quantification
      (iTRAQ), quantitative real-time polymerase chain reaction, gas chromatography,
      and high-performance liquid chromatography, was used to identify proteins,
      measure gene expression levels, volatiles, sugars, organic acids and carotenoids.
      Two thirds of differentially expressed proteins were identified in the pathways
      of glycolysis, citric acid cycle, amino acid, sugar and starch metabolism. An
      enzyme encoding valencene synthase gene (Cstps1) was more abundant in Temple than
      in Murcott. Valencene accounted for 9.4% of total volatile content in Temple,
      whereas no valencene was detected in Murcott fruit. Murcott expression of Cstps1
      is severely reduced. CONCLUSION: We showed that the diversion of valencene and
      other sesquiterpenes into the terpenoid pathway together with high production of
      apocarotenoid volatiles might have resulted in the lower concentration of
      carotenoids in Temple fruit.

PMID- 25848839
TI  - Sarcomere Disruptions of Slow Fiber Resulting From Mountain Ultramarathon.
AB  - OBJECTIVE: To investigate changes after a mountain ultramarathon (MUM) in the
      serum concentration of fast (FM) and slow (SM) myosin isoforms, which are fiber
      type-specific sarcomere proteins. The changes were compared against creatine
      kinase (CK), a widely used fiber-sarcolemma-damage biomarker, and cardiac
      troponin I (cTnI), a widely used cardiac biomarker. METHODS: Observational
      comparison of response in a single group of 8 endurance-trained amateur athletes.
      Time-related changes in serum levels of CK, cTnI, SM, and FM from competitors
      were analyzed before, 1 h after the MUM, and 24 and 48 h after the start of the
      MUM by 1-way ANOVA for repeated measures or Friedman and Wilcoxon tests. Pearson
      correlation coefficient was employed to examine associations between variables.
      RESULTS: While SM was significantly (P = .009) increased in serum 24 h after the
      beginning of the MUM, FM and cTnI did not change significantly. Serum CK activity
      peak was observed 1 h after the MUM (P = .002). Moreover, serum peaks of CK and
      SM were highly correlated (r = .884, P = .004). CONCLUSIONS: Since there is
      evidence of muscle damage after prolonged mountain running, the increase in SM
      serum concentration after a MUM could be indirect evidence of slow- (type I)
      fiber-specific sarcomere disruptions.

PMID- 25848840
TI  - Increased Serum Chemerin Levels in Diabetic Retinopathy of Type 2 Diabetic
      Patients.
AB  - PURPOSE: To compare serum levels of chemerin in type 2 diabetes mellitus (T2DM)
      with or without retinopathy, and to investigate the relationship between serum
      chemerin levels and diabetes retinopathy. MATERIALS AND METHODS: A total of 60
      T2DM patients and 20 healthy subjects (control group) were enrolled in this
      study. Of the T2DM patients, 15 had proliferative diabetic retinopathy (PDR
      group), 20 had non-proliferative retinopathy (NPDR group) and 25 had no
      retinopathy (T2DM group). Their serum samples were collected for testing the
      levels of chemerin, vascular endothelial growth factor (VEGF), C-reactive protein
      (CRP) and so on. The values were analyzed to compare the differences among the
      groups. Simple linear regression analysis and multiple stepwise linear regression
      analysis were used to determine the correlations between variables and chemerin.
      Trend chi-square was used to determine the correlations between chemerin and the
      severity of diabetic retinopathy (DR). RESULTS: Chemerin levels in group PDR,
      NPDR and no DR were 147.56 +/- 35.98 MUg/l, 128.09 +/- 16.33 MUg/l and 113.19 +/-
      19.89 MUg/l, with the significant difference across the three groups (p < 0.05).
      But there was no difference between control group (109.55 +/- 20.98 MUg/l) and
      T2DM group. Simple linear regression show that serum chemerin was correlated with
      duration of diabetes, body mass index (BMI), serum triglycerides, total
      cholesterol, CRP and VEGF, and not correlated with age, systolic and diastolic
      blood pressure in T2DM patients. Stepwise regression analysis showed that BMI,
      CRP and VEGF were significantly associated with serum chemerin (p = 0.006, p =
      0.011 and p = 0.036, respectively). In addition, the more severity of DR as the
      chemerin levels increased (chi(2) = 16.07, p < 0.001). CONCLUSIONS: Serum levels
      of chemerin were significantly increased in the NPDR and PDR group. Elevated
      serum level of chemerin and its positive correlation with BMI, CRP and VEGF
      suggested that chemerin was associated with obesity, inflammation and
      neovascularization and might be involved in the development of DR.

PMID- 25848841
TI  - Can nurses exclude middle-ear effusion without otoscopy in young asymptomatic
      children in primary care?
AB  - OBJECTIVE: Scandinavian guidelines recommend controlling middle-ear effusion
      (MEE) after acute otitis media. The study aim was to determine whether nurses
      without otoscopic experience can reliably exclude MEE with tympanometry or
      spectral gradient acoustic reflectometry (SG-AR) at asymptomatic visits. DESIGN:
      Three nurses were taught to perform examinations with tympanometry and SG-AR.
      Pneumatic otoscopy by the study physician served as the diagnostic standard.
      SETTING: Study clinic at primary health care level. PATIENTS: A total of 156
      children aged 6-35 months. MAIN OUTCOME MEASURES: Predictive values (with 95%
      confidence interval) for tympanometry and SG-AR, and the clinical usefulness,
      i.e. the proportion of visits where nurses obtained the exclusive test result
      from both ears of the child. RESULTS: At 196 visits, the negative predictive
      value of type A and C1 tympanograms (tympanometric peak pressure > -200 daPa) was
      95% (91-97%). Based on type A and C1 tympanograms, the nurse could exclude MEE at
      81/196 (41%) of visits. The negative predictive value of SG-AR level 1 result was
      86% (79-91%). Based on SG-AR level 1 results, the nurse could exclude MEE at
      29/196 (15%) of visits. CONCLUSION: Tympanograms with tympanometric peak pressure
      > -200 daPa (types A and C1) obtained by nurses are reliable test results in
      excluding MEE. However, these test results were obtained at less than half of the
      asymptomatic visits and, thus, the usefulness of excluding MEE by nurses depends
      on the clinical setting.

PMID- 25848842
TI  - Overexpression of a truncated CTF7 construct leads to pleiotropic defects in
      reproduction and vegetative growth in Arabidopsis.
AB  - BACKGROUND: Eco1/Ctf7 is essential for the establishment of sister chromatid
      cohesion during S phase of the cell cycle. Inactivation of Ctf7/Eco1 leads to a
      lethal phenotype in most organisms. Altering Eco1/Ctf7 levels or point mutations
      in the gene can lead to alterations in nuclear division as well as a wide range
      of developmental defects. Inactivation of Arabidopsis CTF7 (AtCTF7) results in
      severe defects in reproduction and vegetative growth. RESULTS: To further
      investigate the function(s) of AtCTF7, a tagged version of AtCTF7 and several
      AtCTF7 deletion constructs were created and transformed into wild type or ctf7 +/
      plants. Transgenic plants expressing 35S:NTAP:AtCTF7?299-345 (AtCTF7?B)
      displayed a wide range of phenotypic alterations in reproduction and vegetative
      growth. Male meiocytes exhibited chromosome fragmentation and uneven chromosome
      segregation. Mutant ovules contained abnormal megasporocyte-like cells during pre
      meiosis, megaspores experienced elongated meiosis and megagametogenesis, and
      defective megaspores/embryo sacs were produced at various stages. The transgenic
      plants also exhibited a broad range of vegetative defects, including meristem
      disruption and dwarfism that were inherited in a non-Mendelian fashion.
      Transcripts for epigenetically regulated transposable elements (TEs) were
      elevated in transgenic plants. Transgenic plants expressing 35S:AtCTF7?B
      displayed similar vegetative defects, suggesting the defects in 35S:NTAP:AtCTF7?B
      plants are caused by high-level expression of AtCTF7?B. CONCLUSIONS: High level
      expression of AtCTF7?B disrupts megasporogenesis, megagametogenesis and male
      meiosis, as well as causing a broad range of vegetative defects, including
      dwarfism that are inherited in a non-Mendelian fashion.

PMID- 25848843
TI  - Local origin of mesenchymal cells in a murine orthotopic lung transplantation
      model of bronchiolitis obliterans.
AB  - Bronchiolitis obliterans is the leading cause of chronic graft failure and long
      term mortality in lung transplant recipients. Here, we used a novel murine model
      to characterize allograft fibrogenesis within a whole-lung microenvironment.
      Unilateral left lung transplantation was performed in mice across varying degrees
      of major histocompatibility complex mismatch combinations. B6D2F1/J (a cross
      between C57BL/6J and DBA/2J) (Haplotype H2b/d) lungs transplanted into DBA/2J
      (H2d) recipients were identified to show histopathology for bronchiolitis
      obliterans in all allogeneic grafts. Time course analysis showed an evolution
      from immune cell infiltration of the bronchioles and vessels at day 14,
      consistent with acute rejection and lymphocytic bronchitis, to subepithelial and
      intraluminal fibrotic lesions of bronchiolitis obliterans by day 28. Allografts
      at day 28 showed a significantly higher hydroxyproline content than the isografts
      (33.21 +/- 1.89 versus 22.36 +/- 2.33 MUg/mL). At day 40 the hydroxyproline
      content had increased further (48.91 +/- 7.09 MUg/mL). Flow cytometric analysis
      was used to investigate the origin of mesenchymal cells in fibrotic allografts.
      Collagen I-positive cells (89.43% +/- 6.53%) in day 28 allografts were H2Db
      positive, showing their donor origin. This novel murine model shows consistent
      and reproducible allograft fibrogenesis in the context of single-lung
      transplantation and represents a major step forward in investigating mechanisms
      of chronic graft failure.

PMID- 25848844
TI  - Peripheral neuromodulation for the treatment of refractory trigeminal neuralgia.
AB  - Trigeminal neuralgia is a type of orofacial pain that is diagnosed in 150,000
      individuals each year, with an incidence of 12.6 per 100,000 person-years and a
      prevalence of 155 cases per 1,000,000 in the United States. Trigeminal neuralgia
      pain is characterized by sudden, severe, brief, stabbing or lancinating,
      recurrent episodes of pain in the distribution of one or more branches of the
      trigeminal nerve, which can cause significant suffering for the affected patient
      population. In many patients, a combination of medication and interventional
      treatments can be therapeutic, but is not always successful. Peripheral nerve
      stimulation has gained popularity as a simple and effective neuromodulation
      technique for the treatment of many pain conditions, including chronic headache
      disorders. Specifically in trigeminal neuralgia, neurostimulation of the
      supraorbital and infraorbital nerves may serve to provide relief of neuropathic
      pain by targeting the distal nerves that supply sensation to the areas of the
      face where the pain attacks occur, producing a field of paresthesia within the
      peripheral distribution of pain through the creation of an electric field in the
      vicinity of the leads. The purpose of the present case report is to introduce a
      new, less-invasive interventional technique, and to describe the authors' first
      experience with supraorbital and infraorbital neurostimulation therapy for the
      treatment of trigeminal neuralgia in a patient who had failed previous
      conservative management. 

PMID- 25848845
TI  - Development and validation of the French-Canadian Chronic Pain Self-efficacy
      Scale.
AB  - BACKGROUND: Perceived self-efficacy is a non-negligible outcome when measuring
      the impact of self-management interventions for chronic pain patients. However,
      no validated, chronic pain-specific self-efficacy scales exist for studies
      conducted with French-speaking populations. OBJECTIVES: To establish the validity
      of the use of the French-Canadian Chronic Pain Self-efficacy Scale (FC-CPSES)
      among chronic pain patients. METHODS: The Chronic Disease Self-Efficacy Scale is
      a validated 33-item self-administered questionnaire that measures perceived self
      efficacy to perform self-management behaviours, manage chronic disease in general
      and achieve outcomes (a six-item version is also available). This scale was
      adapted to the context of chronic pain patients following cross-cultural
      adaptation guidelines. The FC-CPSES was administered to 109 fibromyalgia and 34
      chronic low back pain patients (n=143) who participated in an evidence-based self
      management intervention (the PASSAGE program) offered in 10 health care centres
      across the province of Quebec. Cronbach's alpha coefficients (alpha) were
      calculated to determine the internal consistency of the 33- and six-item versions
      of the FC-CPSES. With regard to convergent construct validity, the association
      between the FC-CPSES baseline scores and related clinical outcomes was examined.
      With regard to the scale's sensitivity to change, pre- and postintervention FC
      CPSES scores were compared. RESULTS: Internal consistency was high for both
      versions of the FC-CPSES (alpha=0.86 to alpha=0.96). Higher self-efficacy was
      significantly associated with higher mental health-related quality of life and
      lower pain intensity and catastrophizing (P<0.05), supporting convergent validity
      of the scale. There was a statistically significant increase in FC-CPSES scores
      between pre- and postintervention measures for both versions of the FC-CPSES
      (P<0.003), which supports their sensitivity to clinical change during an
      intervention. CONCLUSIONS: These data suggest that both versions of the FC-CPSES
      are reliable and valid for the measurement of pain management self-efficacy among
      chronic pain patients.

PMID- 25848846
TI  - Turn-amplitude analysis as a diagnostic test for myofascial syndrome in patients
      with chronic pelvic pain.
AB  - BACKGROUND: Myofascial pain syndrome of the pelvic floor (MPSPF) is a common
      disease in the context of chronic pelvic pain (CPP); however, there is currently
      no gold-standard test to diagnose it. OBJECTIVE: To validate the turns-amplitude
      analysis (TAA) as a diagnostic test for MPSPF in patients with CPP. METHODS: A
      case-control study was performed, and patients were consecutively sampled within
      a specified period of time. A total of 128 patients were included: 64 patients
      with CPP (32 men and 32 women) and 64 control patients (32 men and 32 women). The
      same operator conducted all tests. Electromyography of the TAA is based on the
      collection of motor unit potentials that measure the number of changes in the
      signal and the mean amplitude of the changes. The electromyogram transfers the
      data to a graphical point cloud, which enables the patient's results to be
      compared with the results of the healthy subjects. RESULTS: In patients and
      control subjects, the sensitivity and specificity of the proposed diagnostic test
      showed a marked clinical significance: the sensitivity was 83%, and the
      specificity was 100%. A positive predictive value of 1 (95% CI 1 to 1) and a
      negative predictive value of 0.85 (95% CI 0.77 to 0.93) were observed.
      CONCLUSION: TAA is a reliable diagnostic test to detect MPSPF. Further studies
      are needed to reproduce these results.

PMID- 25848847
TI  - [Nursing activities in family medicine groups for patients with chronic pain].
AB  - INTRODUCTION: Thousands of people treated in primary care are currently
      experiencing chronic pain (CP), for which management is often inadequate. In
      Quebec, nurses in family medicine groups (FMGs) play a key role in the management
      of chronic health problems. OBJECTIVE: The present study aimed to describe the
      activities performed by FMG nurses in relation to CP management and to describe
      barriers to those activities. METHOD: A descriptive correlational cross-sectional
      postal survey was used. The accessible population includes FMG nurses on the
      Ordre des infirmieres et infirmiers du Quebec list. All nurses on the list who
      provided consent to be contacted at home for research purposes were contacted. A
      self-administered postal questionnaire (Pain Management Activities Questionnaire)
      was completed by 53 FMG nurses. RESULTS: Three activities most often performed by
      nurses were to establish a therapeutic relationship with the client; discuss the
      effectiveness of therapeutic measures with the physician; and conduct
      personalized teaching for the patient. The average number of individuals seen by
      interviewed nurses that they believe suffer from CP was 2.68 per week. The lack
      of knowledge of possible interventions in pain management (71.7%) and the
      nonavailability of information on pain management (52.8%) are the main barriers
      perceived by FMG nurses. CONCLUSION: FMG nurses are currently performing few
      activities in CP management. The nonrecognition of CP may explain this situation.

PMID- 25848848
TI  - Comparison of four different pain relief methods during hysterosalpingography: a
      randomized controlled study.
AB  - BACKGROUND: Hysterosalpingography (HSG) is the most commonly used method for
      evaluating the anatomy and patency of the uterine cavity and fallopian tubes, and
      is an important tool in the evaluation of infertility. The most frequent side
      effect is the pain associated with the procedure. OBJECTIVES: To evaluate four
      analgesic methods to determine the most useful method for reducing discomfort
      associated with HSG. METHODS: In the present prospective study, 75 patients
      undergoing HSG for evaluation of infertility were randomly assigned to four
      groups: 550 mg of a nonsteroidal anti-inflammatory drug (NSAID) (group 1); 550 mg
      NSAID + paracervical block (group 2); 550 mg NSAID + paracervical analgesic cream
      (group 3); or 550 mg NSAID + intrauterine analgesic instillation (group 4). A
      visual analogue scale was used to assess the pain perception at five predefined
      steps. RESULTS: Instillation of the liquids used for HSG was found to be the most
      painful step of HSG, and this step was where the only significant difference
      among groups was observed. When comparing visual analogue scale scores, group 2
      and group 3 reported significantly less pain than the other groups. Group 1
      reported significantly higher mean (+/- SD) scores (7.2 +/- 1.6) compared with
      groups 2 and 3 (4.7 +/- 2.5 and 3.8 +/- 2.4, respectively) (P<0.001). In
      addition, group 2 reported significantly less pain than group 4 (4. 7 +/- 2.5
      versus 6.7 +/- 1.8, respectively) (P<0.02). CONCLUSIONS: For effective pain
      relief during HSG, in addition to 550 mg NSAID, local application of lidocaine
      cream to the posterior fornix of the cervix uteri and paracervical lidocaine
      injection into the cervix uteri appear to be the most effective methods.

PMID- 25848849
TI  - The Physcomitrella patens unique alpha-dioxygenase participates in both
      developmental processes and defense responses.
AB  - BACKGROUND: Plant alpha-dioxygenases catalyze the incorporation of molecular
      oxygen into polyunsaturated fatty acids leading to the formation of oxylipins. In
      flowering plants, two main groups of alpha-DOXs have been described. While the
      alpha-DOX1 isoforms are mainly involved in defense responses against microbial
      infection and herbivores, the alpha-DOX2 isoforms are mostly related to
      development. To gain insight into the roles played by these enzymes during land
      plant evolution, we performed biochemical, genetic and molecular analyses to
      examine the function of the single copy moss Physcomitrella patens alpha-DOX
      (Ppalpha-DOX) in development and defense against pathogens. RESULTS: Recombinant
      Ppalpha-DOX protein catalyzed the conversion of fatty acids into 2-hydroperoxy
      derivatives with a substrate preference for alpha-linolenic, linoleic and
      palmitic acids. Ppalpha-DOX is expressed during development in tips of young
      protonemal filaments with maximum expression levels in mitotically active
      undifferentiated apical cells. In leafy gametophores, Ppalpha-DOX is expressed in
      auxin producing tissues, including rhizoid and axillary hairs. Ppalpha-DOX
      transcript levels and Ppalpha-DOX activity increased in moss tissues infected
      with Botrytis cinerea or treated with Pectobacterium carotovorum elicitors. In B.
      cinerea infected leaves, Ppalpha-DOX-GUS proteins accumulated in cells
      surrounding infected cells, suggesting a protective mechanism. Targeted
      disruption of Ppalpha-DOX did not cause a visible developmental alteration and
      did not compromise the defense response. However, overexpressing Ppalpha-DOX, or
      incubating wild-type tissues with Ppalpha-DOX-derived oxylipins, principally the
      aldehyde heptadecatrienal, resulted in smaller moss colonies with less protonemal
      tissues, due to a reduction of caulonemal filament growth and a reduction of
      chloronemal cell size compared with normal tissues. In addition, Ppalpha-DOX
      overexpression and treatments with Ppalpha-DOX-derived oxylipins reduced cellular
      damage caused by elicitors of P. carotovorum. CONCLUSIONS: Our study shows that
      the unique alpha-DOX of the primitive land plant P. patens, although apparently
      not crucial, participates both in development and in the defense response against
      pathogens, suggesting that alpha-DOXs from flowering plants could have originated
      by duplication and successive functional diversification after the divergence
      from bryophytes.

PMID- 25848851
TI  - Water-soluble phosphorescent ruthenium complex with a fluorescent coumarin unit
      for ratiometric sensing of oxygen levels in living cells.
AB  - Dual emission was applied to a molecular probe for the ratiometric sensing of
      oxygen concentration in a living system. We prepared ruthenium complexes
      possessing a coumarin unit (Ru-Cou), in which the (3)MLCT phosphorescence of the
      ruthenium complex was efficiently quenched by molecular oxygen, whereas the
      coumarin unit emitted constant fluorescence independent of the oxygen
      concentration. The oxygen status could be determined precisely from the ratio of
      phosphorescence to fluorescence. We achieved the molecular imaging of cellular
      oxygen levels using Ru-Cou possessing an alkyl chain, which provided appropriate
      lipophilicity to increase cellular uptake. 

PMID- 25848852
TI  - Advanced DNA- and Protein-based Methods for the Detection and Investigation of
      Food Allergens.
AB  - Currently, food allergies are an important health concern worldwide. The presence
      of undeclared allergenic ingredients or the presence of traces of allergens due
      to contamination during food processing poses a great health risk to sensitized
      individuals. Therefore, reliable analytical methods are required to detect and
      identify allergenic ingredients in food products. The present review addresses
      the recent developments regarding the application of DNA- and protein-based
      methods for the detection of allergenic ingredients in foods. The fitness-for
      purpose of reviewed methodology will be discussed, and future trends will be
      highlighted. Special attention will be given to the evaluation of the potential
      of newly developed and promising technologies that can improve the detection and
      identification of allergenic ingredients in foods, such as the use of biosensors
      and/or nanomaterials to improve detection limits, specificity, ease of use, or to
      reduce the time of analysis. Such rapid food allergen test methods are required
      to facilitate the reliable detection of allergenic ingredients by control
      laboratories, to give the food industry the means to easily determine whether its
      product has been subjected to cross-contamination and, simultaneously, to
      identify how and when this cross-contamination occurred.

PMID- 25848850
TI  - Potentiating the cellular targeting and anti-tumor activity of Dp44mT via binding
      to human serum albumin: two saturable mechanisms of Dp44mT uptake by cells.
AB  - Di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT) demonstrates potent
      anti-cancer activity. We previously demonstrated that 14C-Dp44mT enters and
      targets cells through a carrier/receptor-mediated uptake process. Despite
      structural similarity, 2-benzoylpyridine 4-ethyl-3-thiosemicarbazone (Bp4eT) and
      pyridoxal isonicotinoyl hydrazone (PIH) enter cells via passive diffusion.
      Considering albumin alters the uptake of many drugs, we examined the effect of
      human serum albumin (HSA) on the cellular uptake of Dp44mT, Bp4eT and PIH.
      Chelator-HSA binding studies demonstrated the following order of relative
      affinity: Bp4eT~PIH>Dp44mT. Interestingly, HSA decreased Bp4eT and PIH uptake,
      potentially due to its high affinity for the ligands. In contrast, HSA markedly
      stimulated Dp44mT uptake by cells, with two saturable uptake mechanisms
      identified. The first mechanism saturated at 5-10 uM (B(max):1.20+/-0.04 * 107
      molecules/cell; K(d):33+/-3 uM) and was consistent with a previously identified
      Dp44mT receptor/carrier. The second mechanism was of lower affinity, but higher
      capacity (B(max):2.90+/-0.12 * 107 molecules/cell; K(d):65+/-6 uM), becoming
      saturated at 100 uM and was only evident in the presence of HSA. This second
      saturable Dp44mT uptake process was inhibited by excess HSA and had
      characteristics suggesting it was mediated by a specific binding site.
      Significantly, the HSA-mediated increase in the targeting of Dp44mT to cancer
      cells potentiated apoptosis and could be important for enhancing efficacy.

PMID- 25848853
TI  - Do routinely measured risk factors for obesity explain the sex gap in its
      prevalence? Observations from Saudi Arabia.
AB  - BACKGROUND: The prevalence of adult obesity is higher in women than men in most
      countries. However, the pathways that link female sex with excess obesity are
      still not fully understood. We examine whether socioeconomic and behavioural
      factors may mediate the association between sex and obesity in the Saudi Arabian
      setting where there is female excess in obesity. METHODS: We performed a
      mediation analysis using a cross-sectional, national household survey from Saudi
      Arabia with 4758 participants (51% female). A series of multivariable regression
      models were fitted to test if socioeconomic position, physical activity,
      sedentary behaviour, diet, and smoking mediate the association between sex and
      obesity (BMI >=30). The findings were confirmed using causal mediation analysis.
      RESULTS: Women in this sample were roughly twice as likely as men to be obese
      (crude OR 1.9; 95% CI 1.6-2.3). The odds ratio remained significantly higher for
      women compared to men in models testing for mediation (OR range 1.95-2.06). Our
      data suggest that indicators of socio-economic position, physical activity,
      sedentary behaviour, diet, and smoking do not mediate the sex differences in
      obesity. CONCLUSIONS: Our analysis shows that most commonly measured risk factors
      for obesity do not explain the sex differences in its prevalence in the Saudi
      context. Further research is needed to understand what might explain the female
      excess in obesity prevalence. We discuss how data related to the lived experience
      of Saudi men and women may tap into underlying mechanisms by which the sex
      difference in obesity prevalence are produced.

PMID- 25848854
TI  - Integrated pest management of "Golden Delicious" apples.
AB  - Monitoring of plant protection product (PPP) residues in "Golden Delicious"
      apples was performed in 2011-2013, where 216 active substances were analysed with
      three analytical methods. Integrated pest management (IPM) production and
      improved IPM production were compared. Results were in favour of improved IPM
      production. Some active compounds determined in IPM production (boscalid,
      pyraclostrobin, thiacloprid and thiametoxam) were not found in improved IPM
      production. Besides that, in 2011 and 2012, captan residues were lower in
      improved IPM production. Risk assessment was also performed. Chronic exposure of
      consumers was low in general, but showed no major differences for IPM and
      improved IPM production for active substances determined in both types of
      production. Analytical results were compared with the European Union report of
      2010 where 1.3% of apple samples exceeded maximum residue levels (MRLs), while
      MRL exceedances were not observed in this survey. 

PMID- 25848855
TI  - Efficient directional excitation of surface plasmons by a single-element
      nanoantenna.
AB  - Directional light scattering is important in basic research and real
      applications. This area has been successfully downscaled to wavelength and
      subwavelength scales with the development of optical antennas, especially single
      element nanoantennas. Here, by adding an auxiliary resonant structure to a single
      element plasmonic nanoantenna, we show that the highly efficient lowest-order
      antenna mode can be effectively transferred into inactive higher-order modes. On
      the basis of this mode conversion, scattered optical fields can be well
      manipulated by utilizing the interference between different antenna modes. Both
      broadband directional excitation of surface plasmon polaritons (SPPs) and
      inversion of SPP launching direction at different wavelengths are experimentally
      demonstrated as typical examples. The proposed strategy based on mode conversion
      and mode interference provides new opportunities for the design of nanoscale
      optical devices, especially directional nanoantennas. 

PMID- 25848856
TI  - Effects of spring temperatures on the strength of selection on timing of
      reproduction in a long-distance migratory bird.
AB  - Climate change has differentially affected the timing of seasonal events for
      interacting trophic levels, and this has often led to increased selection on
      seasonal timing. Yet, the environmental variables driving this selection have
      rarely been identified, limiting our ability to predict future ecological impacts
      of climate change. Using a dataset spanning 31 years from a natural population of
      pied flycatchers (Ficedula hypoleuca), we show that directional selection on
      timing of reproduction intensified in the first two decades (1980-2000) but
      weakened during the last decade (2001-2010). Against expectation, this pattern
      could not be explained by the temporal variation in the phenological mismatch
      with food abundance. We therefore explored an alternative hypothesis that
      selection on timing was affected by conditions individuals experience when
      arriving in spring at the breeding grounds: arriving early in cold conditions may
      reduce survival. First, we show that in female recruits, spring arrival date in
      the first breeding year correlates positively with hatch date; hence, early
      hatched individuals experience colder conditions at arrival than late-hatched
      individuals. Second, we show that when temperatures at arrival in the recruitment
      year were high, early-hatched young had a higher recruitment probability than
      when temperatures were low. We interpret this as a potential cost of arriving
      early in colder years, and climate warming may have reduced this cost. We thus
      show that higher temperatures in the arrival year of recruits were associated
      with stronger selection for early reproduction in the years these birds were
      born. As arrival temperatures in the beginning of the study increased, but
      recently declined again, directional selection on timing of reproduction showed a
      nonlinear change. We demonstrate that environmental conditions with a lag of up
      to two years can alter selection on phenological traits in natural populations,
      something that has important implications for our understanding of how climate
      can alter patterns of selection in natural populations.

PMID- 25848857
TI  - The Significance of Living Together and Importance of Marriage in Same-Sex
      Couples.
AB  - Because marriage has been denied to same-sex couples, it is likely that the
      meaning and significance ascribed to non-marital cohabitation may be unique.
      Further, it is unclear whether same-sex couples view marriage as important to
      their relationships, and if they do, why. Using qualitative data from 526
      individuals in cohabiting same-sex relationships across 47 states, we explored
      (1) the meaning and significance of cohabitation and (2) the perceived importance
      of legal marriage to the relationship. Participants viewed cohabitation as
      significant, most commonly because it indicates long-term commitment, provides
      emotional support, makes the couple a family, and allows them to share life
      together. Marriage was perceived as important to a majority (90%), most commonly
      because it confers financial and legal benefits, relational legitimacy, and
      demonstrates the same commitment as different-sex couples. Overall, findings
      highlight the symbolic significance of cohabitation and importance of access to
      legal marriage to adults in same-sex relationships. 

PMID- 25848858
TI  - Health and ecological hazards due to natural radioactivity in soil from mining
      areas of Nasarawa State, Nigeria.
AB  - Nasarawa State is located in north central Nigeria and it is known as Nigeria's
      home of solid minerals. It is endowed with barite, copper, zinc, tantalite and
      granite. Continuous releases of mining waste and tailings into the biosphere may
      result in a build-up of radionuclides in air, water and soil. This work therefore
      aims to measure the activity concentration levels of primordial radionuclides in
      the soil/sediment samples collected from selected mines of the mining areas of
      Nasarawa State. The paper also assesses the radiological and radio ecological
      impacts of mining activities on the residents of mining areas and their
      environment. The activity concentrations of primordial radionuclides ((226)Ra,
      (232)Th and (40)K) in the surface soils/sediment samples were determined using
      sodium iodide-thallium gamma spectroscopy. Seven major mines were considered with
      21 samples taken from each of the mines for radiochemistry analysis. The human
      health hazard assessment was conducted using regulatory methodologies set by the
      United Nations Scientific Committee on the Effects of Atomic Radiation, while the
      radio ecological impact assessment was conducted using the ERICA tool v. 1.2. The
      result shows that the activity concentrations of (40)K in the water ways of the
      Akiri copper and the Azara barite mines are 60 and 67% higher than the world
      average value for (40)K, respectively. In all mines, the annual effective dose
      rates (mSv y(-1)) were less than unity, and a maximum annual gonadal dose of 0.58
      mSv y(-1) is received at the Akiri copper mine, which is almost twice the world
      average value for gonadal dose. The external hazard indices for all the mines
      were less than unity. Our results also show that mollusc-gastropod, insect
      larvae, mollusc-bivalve and zooplankton are the freshwater biotas with the
      highest dose rates ranging from 5 to 7 uGy h(-1). These higher dose rates could
      be associated with zinc and copper mining at Abuni and Akiri, respectively. The
      most exposed terrestrial reference organisms are lichen and bryophytes. In all
      cases, the radio ecological risks are not likely to be discernible. This paper
      presents a pioneer data for ecological risk from ionizing contaminants due to
      mining activity in Nasarawa State, Nigeria. Its methodology could be adopted for
      future work on radioecology of mining.

PMID- 25848860
TI  - Importance of suppression of Yb(3+) de-excitation to upconversion enhancement in
      beta-NaYF4: Yb(3+)/Er(3+)@beta-NaYF4 sandwiched structure nanocrystals.
AB  - Nanosized Yb(3+) and Er(3+) co-doped beta-NaYF4 cores coated with multiple beta
      NaYF4 shell layers were synthesized by a solvothermal process. X-ray diffraction
      and scanning electron microscopy were used to characterize the crystal structure
      and morphology of the materials. The visible and near-infrared spectra as well as
      the decay curves were also measured. A 40-fold intensity increase for the green
      upconversion and a 34-fold intensity increase for the red upconversion were
      observed as the cores are coated with three shell layers. The origin of the
      upconversion enhancement was studied on the basis of photoluminescence spectra
      and decay times. Our results indicate that the upconversion enhancement in the
      sandwiched structure mainly originates from the suppression of de-excitation of
      Yb(3+) ions. We also explored the population of the Er(3+4)F9/2 level. The
      results reveal that energy transfer from the lower intermediate Er(3+4)I13/2
      level is dominant for populating the Er(3+4)F9/2 level when the nanocrystal size
      is relatively small; however, with increasing nanocrystal size, the contribution
      of the green emitting Er(3+4)S3/2 level for populating the Er(3+4)F9/2 level,
      which mainly comes from the cross relaxation energy transfer from Er(3+) ions to
      Yb(3+) ions followed by energy back transfer within the same Er(3+)-Yb(3+) pair,
      becomes more and more important. Moreover, this mechanism takes place only in the
      nearest Er(3+)-Yb(3+) pairs. This population route is in good agreement with that
      in nanomaterials and bulk materials. 

PMID- 25848859
TI  - Design and rationale for the randomised, double-blinded, placebo-controlled
      Liraglutide to Improve corONary haemodynamics during Exercise streSS (LIONESS)
      crossover study.
AB  - BACKGROUND: Glucagon-like peptide-1 is an incretin hormone essential for normal
      human glucose homeostasis. Expression of the glucagon-like peptide-1 receptor in
      the myocardium has fuelled growing interest in the direct and indirect
      cardiovascular effects of native glucagon-like peptide-1, its degradation product
      glucagon-like peptide-1(9-36), and the synthetic glucagon-like peptide-1 receptor
      agonists. Preclinical studies have demonstrated cardioprotective actions of all
      three compounds in the setting of experimental myocardial infarction and left
      ventricular systolic dysfunction. This has led to Phase 2 trials of native
      glucagon-like peptide-1 and incretin-based therapies in humans with and without
      Type 2 diabetes mellitus. These studies have demonstrated the ability of glucagon
      like peptide-1, independent of glycaemic control, to positively modulate the
      metabolic and haemodynamic parameters of individuals with coronary artery disease
      and left ventricular systolic dysfunction. We aim to add to this growing body of
      evidence by studying the effect of chronic glucagon-like peptide-1 receptor
      activation on exercise-induced ischaemia in patients with chronic stable angina
      managed conservatively or awaiting revascularisation. The hypothesis being
      liraglutide, a subcutaneously injectable glucagon-like peptide-1 receptor
      agonist, is able to improve exercise haemodynamics in patients with obstructive
      coronary artery disease when compared with saline placebo. METHODS AND DESIGN:
      The Liraglutide to Improve corONary haemodynamics during Exercise streSS
      (LIONESS) trial is an investigator-initiated single-centre randomised double
      blinded placebo-controlled crossover proof-of-principle physiological study.
      Primary endpoints are change in rate pressure product at 0.1 mV ST-segment
      depression and change in degree of ST-segment depression at peak exercise during
      sequential exercise tolerance testing performed over a 6-week study period in
      which 26 patients will be randomised to either liraglutide or saline with
      crossover to the opposing regimen at week 3. DISCUSSION: The study will be
      conducted in accordance with the principles of Good Clinical Practice and the
      Declaration of Helsinki. The local Research Ethics Committee and Medicines and
      Healthcare Products Regulatory Agency have approved the study. TRIAL
      REGISTRATION: National Institute of Health Research Clinical Research Network
      (NIHR CRN) Portfolio ID 11112 and ClinicalTrials.gov Identifier NCT02315001.

PMID- 25848861
TI  - Multigene prognostic tests in breast cancer: past, present, future.
AB  - There is growing consensus that multigene prognostic tests provide useful
      complementary information to tumor size and grade in estrogen receptor (ER)
      positive breast cancers. The tests primarily rely on quantification of ER and
      proliferation-related genes and combine these into multivariate prediction
      models. Since ER-negative cancers tend to have higher proliferation rates, the
      prognostic value of current multigene tests in these cancers is limited. First
      generation prognostic signatures (Oncotype DX, MammaPrint, Genomic Grade Index)
      are substantially more accurate to predict recurrence within the first 5 years
      than in later years. This has become a limitation with the availability of
      effective extended adjuvant endocrine therapies. Newer tests (Prosigna,
      EndoPredict, Breast Cancer Index) appear to possess better prognostic value for
      late recurrences while also remaining predictive of early relapse. Some clinical
      prediction problems are more difficult to solve than others: there are no
      clinically useful prognostic signatures for ER-negative cancers, and drug
      specific treatment response predictors also remain elusive. Emerging areas of
      research involve the development of immune gene signatures that carry modest but
      significant prognostic value independent of proliferation and ER status and
      represent candidate predictive markers for immune-targeted therapies. Overall
      metrics of tumor heterogeneity and genome integrity (for example, homologue
      recombination deficiency score) are emerging as potential new predictive markers
      for platinum agents. The recent expansion of high-throughput technology platforms
      including low-cost sequencing of circulating and tumor-derived DNA and RNA and
      rapid reliable quantification of microRNA offers new opportunities to build
      extended prediction models across multiplatform data. 

PMID- 25848862
TI  - Plant diversity increases soil microbial activity and soil carbon storage.
AB  - Plant diversity strongly influences ecosystem functions and services, such as
      soil carbon storage. However, the mechanisms underlying the positive plant
      diversity effects on soil carbon storage are poorly understood. We explored this
      relationship using long-term data from a grassland biodiversity experiment (The
      Jena Experiment) and radiocarbon ((14)C) modelling. Here we show that higher
      plant diversity increases rhizosphere carbon inputs into the microbial community
      resulting in both increased microbial activity and carbon storage. Increases in
      soil carbon were related to the enhanced accumulation of recently fixed carbon in
      high-diversity plots, while plant diversity had less pronounced effects on the
      decomposition rate of existing carbon. The present study shows that elevated
      carbon storage at high plant diversity is a direct function of the soil microbial
      community, indicating that the increase in carbon storage is mainly limited by
      the integration of new carbon into soil and less by the decomposition of existing
      soil carbon. 

PMID- 25848863
TI  - FOXF2 deficiency promotes epithelial-mesenchymal transition and metastasis of
      basal-like breast cancer.
AB  - INTRODUCTION: Our previous clinical study demonstrated that the under-expression
      of FOXF2 is associated with early-onset metastasis and poor prognosis of patients
      with triple-negative breast cancer. In this study, we further characterized the
      role of FOXF2 in metastasis of basal-like breast cancer (BLBC) and underlying
      molecular mechanisms. METHODS: RT-qPCR, immunoblot, immunofluorescence and
      immunohistochemistry were performed to assess the expression of genes and
      proteins in cell lines and tissues. A series of in vitro and in vivo assays was
      performed in the cells with RNAi-mediated knockdown or overexpression to
      elucidate the function and transcriptional regulatory role of FOXF2 in breast
      cancer. RESULTS: We found that FOXF2 was specifically expressed in most basal
      like breast cells. FOXF2 deficiency enhanced the metastatic ability of BLBC cells
      in vitro and in vivo. Additionally, FOXF2 deficiency induced the epithelial
      mesenchymal transition (EMT) of basal-like breast cells. Furthermore, we
      identified that TWIST1 is a transcriptional target of FOXF2. TWIST1 was
      negatively regulated by FOXF2 and mediated the FOXF2-regulated EMT phenotype of
      basal-like breast cells and aggressive property of BLBC. CONCLUSIONS: FOXF2 is a
      novel EMT-suppressing transcription factor in BLBC. FOXF2 deficiency enhances
      metastatic ability of BLBC cells by activating the EMT program through
      upregulating the transcription of TWIST1.

PMID- 25848864
TI  - The receptor TREML4 amplifies TLR7-mediated signaling during antiviral responses
      and autoimmunity.
AB  - The molecules and pathways that fine-tune innate inflammatory responses mediated
      by Toll-like receptor 7 (TLR7) remain to be fully elucidated. Using an unbiased
      genome-scale screen with short hairpin RNA (shRNA), we identified the receptor
      TREML4 as an essential positive regulator of TLR7 signaling. Macrophages from
      Treml4(-/-) mice were hyporesponsive to TLR7 agonists and failed to produce type
      I interferons due to impaired phosphorylation of the transcription factor STAT1
      by the mitogen-activated protein kinase p38 and decreased recruitment of the
      adaptor MyD88 to TLR7. TREML4 deficiency reduced the production of inflammatory
      cytokines and autoantibodies in MRL/lpr mice, which are prone to systemic lupus
      erythematosus (SLE), and inhibited the antiviral immune response to influenza
      virus. Our data identify TREML4 as a positive regulator of TLR7 signaling and
      provide insight into the molecular mechanisms that control antiviral immunity and
      the development of autoimmunity. 

PMID- 25848865
TI  - Responsiveness of B cells is regulated by the hinge region of IgD.
AB  - Mature B cells express immunoglobulin M (IgM)- and IgD-isotype B cell antigen
      receptors, but the importance of IgD for B cell function has been unclear. By
      using a cellular in vitro system and corresponding mouse models, we found that
      antigens with low valence activated IgM receptors but failed to trigger IgD
      signaling, whereas polyvalent antigens activated both receptor types.
      Investigations of the molecular mechanism showed that deletion of the IgD
      specific hinge region rendered IgD responsive to monovalent antigen, whereas
      transferring the hinge to IgM resulted in responsiveness only to polyvalent
      antigen. Our data suggest that the increased IgD/IgM ratio on conventional B-2
      cells is important for preferential immune responses to antigens in immune
      complexes, and that the increased IgM expression on B-1 cells is essential for B
      1 cell homeostasis and function. 

PMID- 25848868
TI  - Highly Efficient Heterogeneous Hydroformylation over Rh-Metalated Porous Organic
      Polymers: Synergistic Effect of High Ligand Concentration and Flexible Framework.
AB  - A series of diphosphine ligand constructed porous polymers with stable and
      flexible frameworks have been successfully synthesized under the solvothermal
      conditions from polymerizing the corresponding vinyl-functionalized diphosphine
      monomers. These insoluble porous polymers can be swollen by a wide range of
      organic solvents, showing similar behavior to those of soluble analogues. Rather
      than just as immobilizing homogeneous catalysts, these porous polymers supported
      with Rh species demonstrate even better catalytic performance in the
      hydroformylations than the analogue homogeneous catalysts. The sample
      extraordinary performance could be attributed to the combination of high ligand
      concentration and flexible framework of the porous polymers. Meanwhile, they can
      be easily separated and recycled from the reaction systems without losing any
      activity and selectivity. This excellent catalytic performance and easy recycling
      heterogeneous catalyst property make them be very attractive. These diphosphine
      ligand constructed porous polymers may provide new platforms for the
      hydroformylation of olefins in the future. 

PMID- 25848866
TI  - Rapid linkage of innate immunological signals to adaptive immunity by the brain
      fat axis.
AB  - Innate immunological signals induced by pathogen- and/or damage-associated
      molecular patterns are essential for adaptive immune responses, but it is unclear
      if the brain has a role in this process. Here we found that while the abundance
      of tumor-necrosis factor (TNF) quickly increased in the brain of mice following
      bacterial infection, intra-brain delivery of TNF mimicked bacterial infection to
      rapidly increase the number of peripheral lymphocytes, especially in the spleen
      and fat. Studies of various mouse models revealed that hypothalamic responses to
      TNF were accountable for this increase in peripheral lymphocytes in response to
      bacterial infection. Finally, we found that hypothalamic induction of lipolysis
      mediated the brain's action in promoting this increase in the peripheral adaptive
      immune response. Thus, the brain-fat axis is important for rapid linkage of
      innate immunity to adaptive immunity. 

PMID- 25848867
TI  - Let-7 microRNAs target the lineage-specific transcription factor PLZF to regulate
      terminal NKT cell differentiation and effector function.
AB  - Lethal-7 (let-7) microRNAs (miRNAs) are the most abundant miRNAs in the genome,
      but their role in developing thymocytes is unclear. We found that let-7 miRNAs
      targeted Zbtb16 mRNA, which encodes the lineage-specific transcription factor
      PLZF, to post-transcriptionally regulate PLZF expression and thereby the effector
      functions of natural killer T cells (NKT cells). Dynamic upregulation of let-7
      miRNAs during the development of NKT thymocytes downregulated PLZF expression and
      directed their terminal differentiation into interferon-gamma (IFN-gamma)
      producing NKT1 cells. Without upregulation of let-7 miRNAs, NKT thymocytes
      maintained high PLZF expression and terminally differentiated into interleukin 4
      (IL-4)-producing NKT2 cells or IL-17-producing NKT17 cells. Upregulation of let-7
      miRNAs in developing NKT thymocytes was signaled by IL-15, vitamin D and retinoic
      acid. Such targeting of a lineage-specific transcription factor by miRNA
      represents a previously unknown level of developmental regulation in the thymus. 

PMID- 25848869
TI  - Local-global overlap in diversity informs mechanisms of bacterial biogeography.
AB  - Spatial variation in environmental conditions and barriers to organism movement
      are thought to be important factors for generating endemic species, thus
      enhancing global diversity. Recent microbial ecology research suggested that the
      entire diversity of bacteria in the global oceans could be recovered at a single
      site, thus inferring a lack of bacterial endemism. We argue this is not the case
      in the global ocean, but might be in other bacterial ecosystems with higher
      dispersal rates and lower global diversity, like the human gut. We quantified the
      degree to which local and global bacterial diversity overlap in a diverse set of
      ecosystems. Upon comparison of observed local-global diversity overlap with
      predictions from a neutral biogeography model, human-associated microbiomes (gut,
      skin, mouth) behaved much closer to neutral expectations whereas soil, lake and
      marine communities deviated strongly from the neutral expectations. This is
      likely a result of differences in dispersal rate among 'patches', global
      diversity of these systems, and local densities of bacterial cells. It appears
      that overlap of local and global bacterial diversity is surprisingly large (but
      likely not one-hundred percent), and most importantly this overlap appears to be
      predictable based upon traditional biogeographic parameters like community size,
      global diversity, inter-patch environmental heterogeneity and patch connectivity.

PMID- 25848870
TI  - Rapid selective sweep of pre-existing polymorphisms and slow fixation of new
      mutations in experimental evolution of Desulfovibrio vulgaris.
AB  - To investigate the genetic basis of microbial evolutionary adaptation to salt
      (NaCl) stress, populations of Desulfovibrio vulgaris Hildenborough (DvH), a
      sulfate-reducing bacterium important for the biogeochemical cycling of sulfur,
      carbon and nitrogen, and potentially the bioremediation of toxic heavy metals and
      radionuclides, were propagated under salt stress or non-stress conditions for
      1200 generations. Whole-genome sequencing revealed 11 mutations in salt stress
      evolved clone ES9-11 and 14 mutations in non-stress-evolved clone EC3-10. Whole
      population sequencing data suggested the rapid selective sweep of the pre
      existing polymorphisms under salt stress within the first 100 generations and the
      slow fixation of new mutations. Population genotyping data demonstrated that the
      rapid selective sweep of pre-existing polymorphisms was common in salt stress
      evolved populations. In contrast, the selection of pre-existing polymorphisms was
      largely random in EC populations. Consistently, at 100 generations, stress
      evolved population ES9 showed improved salt tolerance, namely increased growth
      rate (2.0-fold), higher biomass yield (1.8-fold) and shorter lag phase (0.7-fold)
      under higher salinity conditions. The beneficial nature of several mutations was
      confirmed by site-directed mutagenesis. All four tested mutations contributed to
      the shortened lag phases under higher salinity condition. In particular, compared
      with the salt tolerance improvement in ES9-11, a mutation in a histidine kinase
      protein gene lytS contributed 27% of the growth rate increase and 23% of the
      biomass yield increase while a mutation in hypothetical gene DVU2472 contributed
      24% of the biomass yield increase. Our results suggested that a few beneficial
      mutations could lead to dramatic improvements in salt tolerance. 

PMID- 25848871
TI  - The diversity and host interactions of Propionibacterium acnes bacteriophages on
      human skin.
AB  - The viral population, including bacteriophages, is an important component of the
      human microbiota, yet is poorly understood. We aim to determine whether
      bacteriophages modulate the composition of the bacterial populations, thus
      potentially playing a role in health or disease. We investigated the diversity
      and host interactions of the bacteriophages of Propionibacterium acnes, a major
      human skin commensal implicated in acne pathogenesis. By sequencing 48 P. acnes
      phages isolated from acne patients and healthy individuals and by analyzing the
      P. acnes phage populations in healthy skin metagenomes, we revealed that P. acnes
      phage populations in the skin microbial community are often dominated by one
      strain. We also found phage strains shared among both related and unrelated
      individuals, suggesting that a pool of common phages exists in the human
      population and that transmission of phages may occur between individuals. To
      better understand the bacterium-phage interactions in the skin microbiota, we
      determined the outcomes of 74 genetically defined Propionibacterium strains
      challenged by 15 sequenced phages. Depending on the Propionibacterium lineage,
      phage infection can result in lysis, pseudolysogeny, or resistance. In type II P.
      acnes strains, we found that encoding matching clustered regularly interspaced
      short palindromic repeat spacers is insufficient to confer phage resistance.
      Overall, our findings suggest that the prey-predator relationship between
      bacteria and phages may have a role in modulating the composition of the
      microbiota. Our study also suggests that the microbiome structure of an
      individual may be an important factor in the design of phage-based therapy. 

PMID- 25848872
TI  - Response of Prochlorococcus to varying CO2:O2 ratios.
AB  - Carbon fixation has a central role in determining cellular redox poise,
      increasingly understood to be a key parameter in cyanobacterial physiology. In
      the cyanobacterium Prochlorococcus-the most abundant phototroph in the
      oligotrophic oceans-the carbon-concentrating mechanism is reduced to the bare
      essentials. Given the ability of Prochlorococcus populations to grow under a wide
      range of oxygen concentrations in the ocean, we wondered how carbon and oxygen
      physiology intersect in this minimal phototroph. Thus, we examined how CO2:O2 gas
      balance influenced growth and chlorophyll fluorescence in Prochlorococcus strain
      MED4. Under O2 limitation, per-cell chlorophyll fluorescence fell at all CO2
      levels, but still permitted substantial growth at moderate and high CO2. Under
      CO2 limitation, we observed little growth at any O2 level, although per-cell
      chlorophyll fluorescence fell less sharply when O2 was available. We explored
      this pattern further by monitoring genome-wide transcription in cells shocked
      with acute limitation of CO2, O2 or both. O2 limitation produced much smaller
      transcriptional changes than the broad suppression seen under CO2 limitation and
      CO2/O2 co-limitation. Strikingly, both CO2 limitation conditions initially evoked
      a transcriptional response that resembled the pattern previously seen in high
      light stress, but at later timepoints we observed O2-dependent recovery of
      photosynthesis-related transcripts. These results suggest that oxygen has a
      protective role in Prochlorococcus when carbon fixation is not a sufficient sink
      for light energy. 

PMID- 25848873
TI  - Single-cell genomics-based analysis of virus-host interactions in marine surface
      bacterioplankton.
AB  - Viral infections dynamically alter the composition and metabolic potential of
      marine microbial communities and the evolutionary trajectories of host
      populations with resulting feedback on biogeochemical cycles. It is quite
      possible that all microbial populations in the ocean are impacted by viral
      infections. Our knowledge of virus-host relationships, however, has been limited
      to a minute fraction of cultivated host groups. Here, we utilized single-cell
      sequencing to obtain genomic blueprints of viruses inside or attached to
      individual bacterial and archaeal cells captured in their native environment,
      circumventing the need for host and virus cultivation. A combination of
      comparative genomics, metagenomic fragment recruitment, sequence anomalies and
      irregularities in sequence coverage depth and genome recovery were utilized to
      detect viruses and to decipher modes of virus-host interactions. Members of all
      three tailed phage families were identified in 20 out of 58 phylogenetically and
      geographically diverse single amplified genomes (SAGs) of marine bacteria and
      archaea. At least four phage-host interactions had the characteristics of late
      lytic infections, all of which were found in metabolically active cells. One
      virus had genetic potential for lysogeny. Our findings include first known
      viruses of Thaumarchaeota, Marinimicrobia, Verrucomicrobia and
      Gammaproteobacteria clusters SAR86 and SAR92. Viruses were also found in SAGs of
      Alphaproteobacteria and Bacteroidetes. A high fragment recruitment of viral
      metagenomic reads confirmed that most of the SAG-associated viruses are abundant
      in the ocean. Our study demonstrates that single-cell genomics, in conjunction
      with sequence-based computational tools, enable in situ, cultivation-independent
      insights into host-virus interactions in complex microbial communities. 

PMID- 25848874
TI  - Single-cell genomics of a rare environmental alphaproteobacterium provides unique
      insights into Rickettsiaceae evolution.
AB  - The bacterial family Rickettsiaceae includes a group of well-known etiological
      agents of many human and vertebrate diseases, including epidemic typhus-causing
      pathogen Rickettsia prowazekii. Owing to their medical relevance, rickettsiae
      have attracted a great deal of attention and their host-pathogen interactions
      have been thoroughly investigated. All known members display obligate
      intracellular lifestyles, and the best-studied genera, Rickettsia and Orientia,
      include species that are hosted by terrestrial arthropods. Their obligate
      intracellular lifestyle and host adaptation is reflected in the small size of
      their genomes, a general feature shared with all other families of the
      Rickettsiales. Yet, despite that the Rickettsiaceae and other Rickettsiales
      families have been extensively studied for decades, many details of the origin
      and evolution of their obligate host-association remain elusive. Here we report
      the discovery and single-cell sequencing of 'Candidatus Arcanobacter lacustris',
      a rare environmental alphaproteobacterium that was sampled from Damariscotta Lake
      that represents a deeply rooting sister lineage of the Rickettsiaceae.
      Intriguingly, phylogenomic and comparative analysis of the partial 'Candidatus
      Arcanobacter lacustris' genome revealed the presence chemotaxis genes and
      vertically inherited flagellar genes, a novelty in sequenced Rickettsiaceae, as
      well as several host-associated features. This finding suggests that the ancestor
      of the Rickettsiaceae might have had a facultative intracellular lifestyle. Our
      study underlines the efficacy of single-cell genomics for studying microbial
      diversity and evolution in general, and for rare microbial cells in particular. 

PMID- 25848875
TI  - Size-fraction partitioning of community gene transcription and nitrogen
      metabolism in a marine oxygen minimum zone.
AB  - The genetic composition of marine microbial communities varies at the microscale
      between particle-associated (PA; >1.6 MUm) and free-living (FL; 0.2-1.6 MUm)
      niches. It remains unclear, however, how metabolic activities differ between PA
      and FL fractions. We combined rate measurements with metatranscriptomics to
      quantify PA and FL microbial activity in the oxygen minimum zone (OMZ) of the
      Eastern Tropical North Pacific, focusing on dissimilatory processes of the
      nitrogen (N) cycle. Bacterial gene counts were 8- to 15-fold higher in the FL
      compared with the PA fraction. However, rates of all measured N cycle processes,
      excluding ammonia oxidation, declined significantly following particle (>1.6 MUm)
      removal. Without particles, rates of nitrate reduction to nitrite (1.5-9.4nMNd(
      1)) fell to zero and N2 production by denitrification (0.5-1.7nMNd(-1)) and
      anammox (0.3-1.9nMNd(-1)) declined by 53-85%. The proportional representation of
      major microbial taxa and N cycle gene transcripts in metatranscriptomes followed
      fraction-specific trends. Transcripts encoding nitrate reductase were uniform
      among PA and FL fractions, whereas anammox-associated transcripts were
      proportionately enriched up to 15-fold in the FL fraction. In contrast,
      transcripts encoding enzymes for N2O and N2 production by denitrification were
      enriched up to 28-fold in PA samples. These patterns suggest that the majority of
      N cycle activity, excluding N2O and N2 production by denitrification, is confined
      to a FL majority that is critically dependent on access to particles, likely as a
      source of organic carbon and inorganic N. Variable particle distributions may
      drive heterogeneity in N cycle activity and gene expression in OMZs.

PMID- 25848877
TI  - Acute kidney injury: Mitsugumin 53 mediates repair of the damaged proximal
      tubular epithelium.

PMID- 25848876
TI  - Growth phase-specific evolutionary benefits of natural transformation in
      Acinetobacter baylyi.
AB  - Natural transformation in bacteria facilitates the uptake and genomic integration
      of exogenous DNA. This allows horizontal exchange of adaptive traits not easily
      achieved by point mutations, and has a major role in the acquisition of adaptive
      traits exemplified by antibiotic resistance determinants and vaccination escape.
      Mechanisms of DNA uptake and genomic integration are well described for several
      naturally transformable bacterial species; however, the selective forces
      responsible for its evolution and maintenance are still controversial. In this
      study we evolved transformation-proficient and -deficient Acinetobacter baylyi
      for 175 days in serial transfer cultures where stress was included. We found that
      natural transformation-proficient populations adapted better to active growth and
      early stationary phase. This advantage was offset by the reduced performance in
      the late stationary/death phase. We demonstrate fitness trade-offs between
      adaptation to active growth and survival in stationary/death phase caused by
      antagonistic pleiotropy. The presented data suggest that the widely held
      assumption that recombination speeds up adaptation by rapid accumulation of
      multiple adaptive mutations in the same genetic background is not sufficient to
      fully account for the maintenance of natural transformation in bacteria. 

PMID- 25848878
TI  - Glomerular disease: Efficacy of corticosteroids in high-risk IgA nephropathy.

PMID- 25848879
TI  - Genetics: Strong association of APOL1 risk variants with HIV-associated
      nephropathy in black South Africans.

PMID- 25848880
TI  - Hypertension: Impact of blood pressure lowering in type 2 diabetes.

PMID- 25848882
TI  - Random-Coil Behavior of Chemically Denatured Topologically Knotted Proteins
      Revealed by Small-Angle X-ray Scattering.
AB  - Recent studies on the mechanisms by which topologically knotted proteins attain
      their natively knotted structures have intrigued theoretical and experimental
      biophysicists. Of particular interest is the finding that YibK and YbeA, two
      small trefoil knotted proteins, remain topologically knotted in their chemically
      denatured states. Using small-angle X-ray scattering (SAXS), we examine whether
      these chemically denatured knotted proteins are different from typical random
      coils. By revisiting the scaling law of radius of gyration (Rg) as a function of
      polypeptide chain length for chemically denatured proteins and natively folded
      proteins, we find that the chemically denatured knotted proteins in fact follow
      the same random coil-like behavior, suggesting that the formation of topological
      protein knots do not necessarily require global compaction while the loosely
      knotted polypeptide chains are capable of maintaining the correct chirality
      without defined secondary or tertiary structures. 

PMID- 25848881
TI  - Haemodialysis-induced hypoglycaemia and glycaemic disarrays.
AB  - In patients with diabetes receiving chronic haemodialysis, both very high and low
      glucose levels are associated with poor outcomes, including mortality. Conditions
      that are associated with an increased risk of hypoglycaemia in these patients
      include decreased gluconeogenesis in the remnant kidneys, deranged metabolic
      pathways, inadequate nutrition, decreased insulin clearance, glucose loss to the
      dialysate and diffusion of glucose into erythrocytes during haemodialysis.
      Haemodialysis-induced hypoglycaemia is common during treatments with glucose-free
      dialysate, which engenders a catabolic status similar to fasting; this state can
      also occur with 5.55 mmol/l glucose-containing dialysate. Haemodialysis-induced
      hypoglycaemia occurs more frequently in patients with diabetes than in those
      without. Insulin therapy and oral hypoglycaemic agents should, therefore, be used
      with caution in patients on dialysis. Several hours after completion of
      haemodialysis treatment a paradoxical rebound hyperglycaemia may occur via a
      similar mechanism as the Somogyi effect, together with insulin resistance.
      Appropriate glycaemic control tailored for patients on haemodialysis is needed to
      avoid haemodialysis-induced hypoglycaemia and other glycaemic disarrays. In this
      Review we summarize the pathophysiology and current management of glycaemic
      disarrays in patients on haemodialysis. 

PMID- 25848883
TI  - High definition bronchoscopy: a randomized exploratory study of diagnostic value
      compared to standard white light bronchoscopy and autofluorescence bronchoscopy.
AB  - BACKGROUND: Videobronchoscopy is an essential diagnostic procedure for evaluation
      of the central airways and pivotal for the diagnosis and staging of lung cancer.
      Technological improvements have resulted in high definition (HD) images with
      advanced real time image enhancement techniques (i-scan). OBJECTIVES: In this
      study we aimed to explore the sensitivity of HD+ i-scan bronchoscopy for
      detection of epithelial changes like vascular abnormalities and suspicious
      preinvasive lesions, and tumors. METHODS: In patients scheduled for a therapeutic
      or diagnostic procedure under general anesthesia videos of the bronchial tree
      were made using 5 videobronchoscopy modes in random order: normal white light
      videobronchoscopy (WLB), HD-bronchoscopy (HD), HD bronchoscopy with surface
      enhancement technique (i-scan1), HD with surface- and tone enhancement technique
      (i-scan2) and dual mode autofluorescence videobronchoscopy (AFB). The videos were
      scored in random order by two independent and blinded expert bronchoscopists.
      RESULTS: In 29 patients all videos were available for analysis. Vascular
      abnormalities were scored most frequently in HD + i-scan2 bronchoscopy (1.33 +/-
      0.29 abnormal or suspicious sites per patient) as compared to 0.12 +/- 0.05 site
      for AFB (P = 0.003). Sites suspicious for preinvasive lesions were most
      frequently reported using AFB (0.74 +/- 0.12 sites per patient) as compared to
      0.17 +/- 0.06 for both WLB and HD bronchoscopy (P = 0.003). Tumors were detected
      equally by all modalities. The preferred modality was HD bronchoscopy with i-scan
      (tone- plus surface and surface enhancement in respectively 38% and 35% of cases
      P = 0.006). CONCLUSIONS: This study shows that high definition bronchoscopy with
      image enhancement technique may result in better detection of subtle vascular
      abnormalities in the airways. Since these abnormalities may be related to
      preneoplastic lesions and tumors this is of clinical relevance. Further
      investigations using this technique relating imaging to histology are warranted.

PMID- 25848885
TI  - Detection of endogenous and food-derived collagen dipeptide prolylhydroxyproline
      (Pro-Hyp) in allergic contact dermatitis-affected mouse ear.
AB  - Generation of collagen dipeptides and deposition of orally administered
      prolylhydroxyproline (Pro-Hyp) in local inflammatory sites were examined in mice
      with hapten (2,4-dinitrofluorobenzene)-induced dermatitis in the ear. Pro-Hyp
      content in the hapten-treated ear was significantly higher in the chronic phase
      of contact dermatitis than the vehicle control. In contrast, hydroxyprolylglycine
      contents remained at lower levels in all cases compared to Pro-Hyp. Four hours
      after the ingestion of [(13)C5,(15)N]Pro and [(13)C5,(15)N]Pro-Hyp, labeled-Pro
      Hyp and Pro, respectively, appeared only in the ear with dermatitis. Thus, Pro
      Hyp is generated and degraded as part of the rapid synthesis and degradation of
      collagen in the ear with dermatitis. In addition to the endogenously generated
      Pro-Hyp, the orally administered Pro-Hyp was deposited in the ears. 

PMID- 25848886
TI  - Is art therapy a reliable tool for rehabilitating people suffering from
      brain/mental diseases?
AB  - Whether art therapy can be an effective rehabilitative treatment for people with
      brain or mental diseases (e.g., dementia, Alzheimer's disease, Parkinson's
      disease, autism, schizophrenia) is a long-standing and highly debated issue. On
      the one hand, several observational studies and anecdotal evidence
      enthusiastically support the effectiveness of arts-based therapy. On the other
      hand, few rigorous clinical investigations have been performed, and there is too
      little empirical evidence to allow a full assessment of the risks and benefits of
      this intervention. Nevertheless, there is a progressively increasing demand for
      the development of appropriate complementary therapies to improve the personal
      and social lives of patients with neurodegenerative diseases. This is because
      conventional medical treatments are aimed at alleviating symptoms but cannot
      arrest or reverse the degenerative process. Thus, as disease progresses and
      adverse effects emerge, patients' quality of life dramatically decreases; when
      this occurs patients seek different forms of intervention. Art therapy is a
      potentially appealing treatment because of its more holistic approach to
      healthcare. However, as with any medicine, its effects must be tested by using
      standard, rigorous scientific approaches. This report describes the current state
      of research into art therapy and outlines many key factors that future research
      should consider, all of which are directly or indirectly related to the neural
      mechanism underlying behavioral changes: brain plasticity. Artistic performance
      could promote some form of brain plasticity that, to some extent, might
      compensate for the brain damage caused by the disease. 

PMID- 25848884
TI  - Pleiotropic effect of chromosome 5A and the mvp mutation on the metabolite
      profile during cold acclimation and the vegetative/generative transition in
      wheat.
AB  - BACKGROUND: Wheat is the leading source of vegetable protein in the human diet,
      and metabolites are crucial for both plant development and human nutrition. The
      recent advances in metabolomics provided an opportunity to perform an untargeted
      metabolite analysis in this important crop. RESULTS: Wheat was characterised at
      the metabolite level during cold acclimation and transition from the vegetative
      to the generative phase. The relationship between these changes and chromosome 5A
      and the maintained vegetative phase (mvp) mutation was also investigated. Samples
      were taken from the shoots and crowns during four developmental stages: plants
      grown at 20/17 degrees C, after cold treatment but still during the vegetative
      phase, at the double ridge and during spikelet formation. The levels of 47
      compounds were identified by gas chromatography-mass spectrometry, of which 38
      were annotated. The cold treatment, in general, increased the concentrations of
      osmolites but not in all lines and not equally in the shoots and crowns. The
      accumulation of proline was not associated with the vernalisation process or with
      frost tolerance. The mvp mutation and chromosome 5A substitutions altered the
      amounts of several metabolites compared to those of the Tm and CS, respectively,
      during each developmental stage. The Ch5A substitution resulted in more
      substantial changes at the metabolite level than did the Tsp5A substitution.
      While Ch5A mainly influenced the sugar concentrations, Tsp5A altered the level of
      tricarboxylic acid cycle intermediates during the vegetative/generative
      transition. A much higher trehalose, proline, glutamine, asparagine, and
      unidentified m/z 186 content was detected in crowns than in shoots that may
      contribute to the frost tolerance of crowns. CONCLUSIONS: Substantial influences
      of chromosome 5A and the mvp mutation on metabolism during four different
      developmental stages were demonstrated. The distinct and overlapping accumulation
      patterns of metabolites suggest the complex genetic regulation of metabolism in
      the shoots and crowns.

PMID- 25848888
TI  - Regenerable fluorescent nanosensors for monitoring and recovering metal ions
      based on photoactivatable monolayer self-assembly and host-guest interactions.
AB  - Efficient detection, removal, and recovery of heavy metal ions from aqueous
      environments represents a technologically challenging and ecologically urgent
      question in the face of increasing metal-related pollution and poisoning across
      the globe. Although small-molecule and entrapment-based nanoparticle sensors have
      been extensively explored for metal detection, neither of these extant strategies
      satisfies the critical needs for high-performance sensors that are inexpensive,
      efficient, and recyclable. Here we first report the development of a regenerable
      fluorescent nanosensor system for the selective and sensitive detection of
      multiple heavy metal ions, based on light-switchable monolayer self-assembly and
      host-guest interactions. The system exploits photocontrolled inclusion and
      exclusion responses of an alpha-cyclodextrin (CD)-containing surface conjugated
      with photoisomerizable azobenzene as a supramolecular system that undergoes
      reversible assembly and disassembly. The metal nanosensors can be facilely
      fabricated and photochemically switched between three chemically distinct
      entities, each having an excellent capacity for selective detecting specific
      metal ions (namely, Cu(2+), Fe(3+), Hg(2+)) in a chemical system and in assays on
      actual water samples with interfering contaminants. 

PMID- 25848887
TI  - Anticancer and antiangiogenic activity of surfactant-free nanoparticles based on
      self-assembled polymeric derivatives of vitamin E: structure-activity
      relationship.
AB  - alpha-Tocopheryl succinate (alpha-TOS) is a well-known mitochondrially targeted
      anticancer compound, however, it is highly hydrophobic and toxic. In order to
      improve its activity and reduce its toxicity, new surfactant-free biologically
      active nanoparticles (NP) were synthesized. A methacrylic derivative of alpha-TOS
      (MTOS) was prepared and incorporated in amphiphilic pseudoblock copolymers when
      copolymerized with N-vinylpyrrolidone (VP) by free radical polymerization
      (poly(VP-co-MTOS)). The selected poly(VP-co-MTOS) copolymers formed surfactant
      free NP by nanoprecipitation with sizes between 96 and 220 nm and narrow size
      distribution, and the in vitro biological activity was tested. In order to
      understand the structure-activity relationship three other methacrylic monomers
      were synthesized and characterized: MVE did not have the succinate group, SPHY
      did not have the chromanol ring, and MPHY did not have both the succinate group
      and the chromanol ring. The corresponding families of copolymers (poly(VP-co
      MVE), poly(VP-co-SPHY), and poly(VP-co-MPHY)) were synthesized and characterized,
      and their biological activity was compared to poly(VP-co-MTOS). Both poly(VP-co
      MTOS) and poly(VP-co-MVE) presented triple action: reduced cell viability of
      cancer cells with little or no harm to normal cells (anticancer), reduced
      viability of proliferating endothelial cells with little or no harm to quiescent
      endothelial cells (antiangiogenic), and efficiently encapsulated hydrophobic
      molecules (nanocarrier). The anticancer and antiangiogenic activity of the
      synthesized copolymers is demonstrated as the active compound (vitamin E or alpha
      tocopheryl succinate) do not need to be cleaved to trigger the biological action
      targeting ubiquinone binding sites of complex II. Poly(VP-co-SPHY) and poly(VP-co
      MPHY) also formed surfactant-free NP that were also endocyted by the assayed
      cells; however, these NP did not selectively reduce cell viability of cancer
      cells. Therefore, the chromanol ring of the vitamin E analogues has an important
      role in the biological activity of the copolymers. Moreover, when succinate
      moiety is substituted and vitamin E is directly linked to the macromolecular
      chain through an ester bond, the biological activity is maintained. 

PMID- 25848889
TI  - Phototropism in gametophytic shoots of the moss Physcomitrella patens.
AB  - Shoot phototropism enables plants to position their photosynthetic organs in
      favorable light conditions and thus benefits growth and metabolism in land
      plants. To understand the evolution of this response, we established an
      experimental system to study phototropism in gametophores of the moss
      Physcomitrella patens. The phototropic response of gametophores occurs slowly; a
      clear response takes place more than 24 hours after the onset of unilateral light
      irradiation, likely due to the slow growth rate of gametophores. We also found
      that red and far-red light can induce phototropism, with blue light being less
      effective. These results suggest that plants used a broad range of light
      wavelengths as phototropic signals during the early evolution of land plants. 

PMID- 25848890
TI  - Antioxidant vitamin C prevents decline in endothelial function during sitting.
AB  - BACKGROUND: This study was designed to test the hypothesis that antioxidant
      Vitamin C prevents the impairment of endothelial function during prolonged
      sitting. MATERIAL AND METHODS: Eleven men (24.2 +/- 4.4 yrs) participated in 2
      randomized 3-h sitting trials. In the sitting without vitamin C (SIT) and the
      sitting with vitamin C (VIT) trial, participants were seated for 3 h without
      moving their legs. Additionally, in the VIT trial, participants ingested 2
      vitamin C tablets (1 g and 500 mg) at 30 min and 1 h 30 min, respectively.
      Superficial femoral artery (SFA) flow-mediated dilation (FMD) was measured hourly
      for 3 h. RESULTS: By a 1-way ANOVA, there was a significant decline in FMD during
      3 h of SIT (p<0.001). Simultaneously, there was a significant decline in
      antegrade (p=0.04) and mean (0.037) shear rates. For the SIT and VIT trials by a
      2-way (trial x time) repeated measures ANOVA, there was a significant interaction
      (p=0.001). Pairwise testing revealed significant between-SFA FMD in the SIT and
      VIT trial at each hour after baseline, showing that VIT prevented the decline in
      FMD 1 h (p=0.009), 2 h (p=0.016), and 3 h (p=0.004). There was no difference in
      the shear rates between SIT and VIT trials (p>0.05). CONCLUSIONS: Three hours of
      sitting resulted in impaired SFA FMD. Antioxidant Vitamin C prevented the decline
      in SFA FMD, suggesting that oxidative stress may contribute to the impairment in
      endothelial function during sitting.

PMID- 25848891
TI  - Phytoremediation of Cd, Ni, Pb and Zn by Salvinia minima.
AB  - Most metals disperse easily in environments and can be bioconcentrated in tissues
      of many organisms causing risks to the health and stability of aquatic ecosystems
      even at low concentrations. The use of plants to phytoremediation has been
      evaluated to mitigate the environmental contamination by metals since they have
      large capacity to adsorb or accumulate these elements. In this study we evaluate
      Salvinia minima growth and its ability to accumulate metals. The plants were
      cultivated for about 60 days in different concentrations of Cd, Ni, Pb and Zn
      (tested alone) in controlled environmental conditions and availability of
      nutrients. The results indicated that S. minima was able to grow in low
      concentrations of selected metals (0.03 mg L(-1) Cd, 0.40 mg L(-1) Ni, 1.00 mg L(
      1) Pb and 1.00 mg L(-1) Zn) and still able to adsorb or accumulate metals in
      their tissues when cultivated in higher concentrations of selected metals without
      necessarily grow. The maximum values of removal metal rates (mg m(2) day(-1)) for
      each metal (Cd = 0.0045, Ni = 0.0595, Pb = 0.1423 e Zn = 0.4046) are listed. We
      concluded that S. minima may be used as an additional tool for metals removal
      from effluent.

PMID- 25848892
TI  - The Function of Matricellular Proteins in the Lamina Cribrosa and Trabecular
      Meshwork in Glaucoma.
AB  - PURPOSE: To review the current literature regarding the role of matricellular
      proteins in glaucoma, specifically in the lamina cribrosa (LC) region of the
      optic nerve head (ONH) and the trabecular meshwork (TM). METHODS: A literature
      search was performed for published articles describing the expression and
      function of matricellular proteins such as thrombospondin (TSP), connective
      tissue growth factor (CTGF), secreted protein acidic and rich in cysteine
      (SPARC), and periostin in glaucoma. RESULTS: In glaucoma, there are
      characteristic extracellular matrix (ECM) changes associated with optic disc
      cupping in the ONH and subsequent visual field defects. Matricellular proteins
      are a family of nonstructural secreted glycoproteins, which enable cells to
      communicate with their surrounding ECM, including CTGF, also known as CCN2, TSPs,
      SPARC, periostin, osteonectin, and tenascin-C and -X, and other ECM proteins.
      Such proteins appear to play a role in fibrosis and increased ECM deposition.
      Importantly, most are widely expressed in tissues particularly in the TM and ONH,
      and deficiency of TSP1 and SPARC has been shown to lower intraocular pressure in
      mouse models of glaucoma through enhanced outflow facility. CONCLUSION: This
      article highlights the role of matricellular proteins in glaucoma pathology. The
      potential role of these proteins in glaucoma is emerging as some have an
      association with the pathophysiology of the TM and LC region and might therefore
      be potential targets for therapeutic intervention in glaucoma.

PMID- 25848893
TI  - Neuromuscular Fatigue and Muscle Damage After a Women's Rugby Sevens Tournament.
AB  - PURPOSE: To examine relationships between on-field game movement patterns and
      changes in markers of neuromuscular fatigue and muscle damage during a 2-d
      women's rugby sevens tournament. METHODS: Female national (mean +/- SD n = 12,
      22.3 +/- 2.5 y, 1.67 +/- 0.04 m, 65.8 +/- 4.6 kg) and state (n = 10, 24.4 +/- 4.3
      y, 1.67 +/- 0.03 m, 66.1 +/- 7.9 kg) representative players completed baseline
      testing for lower-body neuromuscular function (countermovement-jump [CMJ] test),
      muscle damage (capillary creatine kinase [CK]), perceived soreness, and perceived
      recovery. Testing was repeated after games on days 1 and 2 of the tournament. GPS
      (5-Hz) data were collected throughout the tournament (4-6 games/player). RESULTS:
      National players were involved in greater on-field movements for total time,
      distance, high-speed running (>5 m/s), and impacts >10 g (effect size [ES] = 0.55
      0.97) and displayed a smaller decrement in performance from day 1 to day 2.
      Despite this, state players had a much greater 4-fold increase (deltaCK = 737
      U/L) in CK compared with the 2-fold increase (deltaCK = 502 U/L) in national
      players (ES = 0.73). Both groups had similar perceived soreness and recovery
      while CMJ performance was unchanged. High-speed running and impacts >10 g were
      largely correlated (r = .66-.91) with deltaCK for both groups. CONCLUSION: A 2
      day women's rugby sevens tournament elicits substantial muscle damage; however,
      there was little change in lower-body neuromuscular function. Modest increases in
      CK can largely be attributed to high-speed running and impacts >10 g that players
      typically endure.

PMID- 25848894
TI  - The transcriptome of Utricularia vulgaris, a rootless plant with minimalist
      genome, reveals extreme alternative splicing and only moderate sequence
      similarity with Utricularia gibba.
AB  - BACKGROUND: The species of Utricularia attract attention not only owing to their
      carnivorous lifestyle, but also due to an elevated substitution rate and a
      dynamic evolution of genome size leading to its dramatic reduction. To better
      understand the evolutionary dynamics of genome size and content as well as the
      great physiological plasticity in this mostly aquatic carnivorous genus, we
      analyzed the transcriptome of Utricularia vulgaris, a temperate species with well
      characterized physiology and ecology. We compared its transcriptome, namely gene
      content and overall transcript profile, with a previously described transcriptome
      of Utricularia gibba, a congener possessing one of the smallest angiosperm
      genomes. RESULTS: We sequenced a normalized cDNA library prepared from total RNA
      extracted from shoots of U. vulgaris including leaves and traps, cultivated under
      sterile or outdoor conditions. 454 pyrosequencing resulted in more than 1,400,000
      reads which were assembled into 41,407 isotigs in 19,522 isogroups. We observed
      high transcript variation in several isogroups explained by multiple loci and/or
      alternative splicing. The comparison of U. vulgaris and U. gibba transcriptomes
      revealed a similar distribution of GO categories among expressed genes, despite
      the differences in transcriptome preparation. We also found a strong
      correspondence in the presence or absence of root-associated genes between the U.
      vulgaris transcriptome and U. gibba genome, which indicated that the loss of some
      root-specific genes had occurred before the divergence of the two rootless
      species. CONCLUSIONS: The species-rich genus Utricularia offers a unique
      opportunity to study adaptations related to the environment and carnivorous habit
      and also evolutionary processes responsible for considerable genome reduction. We
      show that a transcriptome may approximate the genome for gene content or gene
      duplication estimation. Our study is the first comparison of two global sequence
      data sets in Utricularia.

PMID- 25848895
TI  - Upward communication about cancer screening: adolescent daughter to mother.
AB  - Substantial breast and cervical cancer disparities exist in the United States,
      particularly among African American women with low socioeconomic status. There is
      considerable potential for discussions about cancer prevention between mothers
      and daughters. However, upward communication, from child to parent, remains a
      relatively novel research area, and it remains unclear how receptive mothers
      would be to messages from their daughter about cancer, a topic that may be
      considered culturally inappropriate for daughters to initiate. In this study, the
      authors simulated cancer message delivery to daughters and then conducted direct
      observation of daughters as they recalled and shared the message with their
      mother or female elder. The authors found that daughters were able to
      successfully recall and deliver a cancer appeal to their mother and mothers were
      generally receptive to this message. Not only did mothers listen to their
      daughters' appeals, but also daughters' knowledge of cancer was considerably
      improved by the opportunity to educate her female elder. Moreover, daughters'
      nonverbal communication suggested a surprisingly relaxed demeanor. The potential
      of young people to have an effect on the screening behavior of their female
      elders is very promising in terms of reducing cancer disparities. 

PMID- 25848897
TI  - Efficacy and Safety of Radiofrequency Ablation for Treatment of Locally Recurrent
      Thyroid Cancers Smaller than 2 cm.
AB  - PURPOSE: To evaluate the efficacy and safety of radiofrequency ablation (RFA) for
      localized small recurrent thyroid cancers less than 2 cm by comparing them with
      those at repeat surgery. MATERIALS AND METHODS: This retrospective study was
      institutional review board-approved, and informed consent was waived. From
      December 2008 to December 2011, this study evaluated 73 patients (17 men and 56
      women; age, 50.3 years +/- 13.6) with recurrent thyroid cancer who had been
      treated with RFA (n = 27) or repeat surgery (n = 46) who met the following
      criteria: (a) three or fewer recurrences or lesions with high probability of
      recurrence at ultrasonography; (b) no tumor other than the target tumors; and (c)
      at least 1 year of follow-up. RFA was recommended and performed in cases of
      surgical ineligibility, such as patient refusal and poor medical condition.
      Recurrence-free survival rates and posttreatment complication rates (eg,
      hoarseness and hypocalcemia) were compared between RFA and reoperation groups
      after adjustment with weighted analysis by using inverse probability of treatment
      weights. RESULTS: After this adjustment, the 1- and 3-year recurrence-free
      survival rates were comparable (P = .681) for RFA (96.0% and 92.6%, respectively)
      and reoperation (92.2% and 92.2%, respectively) groups. The posttreatment
      hoarseness rate did not differ between the RFA (7.3% [1.8 of 24]) and reoperation
      (9.0% [3.6 of 39.5]) groups (P = .812), and posttreatment hypocalcemia occurred
      exclusively in the reoperation group (11.6% [4.6 of 39.5]) but not in the RFA
      group (0% [0 of 24]) (P = .083). CONCLUSION: RFA may be an effective and safe
      alternative to repeat surgery in patients with locally recurrent small thyroid
      cancers.

PMID- 25848898
TI  - Integrated FDG PET/MR Imaging for the Assessment of Myocardial Salvage in
      Reperfused Acute Myocardial Infarction.
AB  - PURPOSE: To compare the size of the area with reduced myocardial
      fluorodeoxygluose (FDG) uptake with the endocardial surface area (ESA) method as
      a marker for the area at risk in patients with reperfused acute myocardial
      infarction. MATERIALS AND METHODS: The study was approved by the local
      institutional review board. All patients gave written informed consent prior to
      their examination. Twenty-five patients (mean age +/- standard deviation, 54
      years +/- 14) underwent prospective cardiac positron emission tomography/magnetic
      resonance imaging after acute coronary occlusion and interventional reperfusion.
      On late gadolinium contrast enhancement images, the size of infarction and the
      area at risk, as determined with ESA, were assessed and compared with the area of
      reduced FDG uptake. Statistical analysis comprised paired t tests and Mann
      Whitney U tests, as well as Pearson r and Spearman rho for correlations. RESULTS:
      In patients with infarcted myocardium and reduced FDG uptake (n = 18), a good
      correlation between the area of reduced FDG uptake and the area at risk according
      to ESA was observed (r = .70, P = .001). The area of reduced FDG uptake (31% +/-
      11 of left ventricular myocardial mass) was larger than the size of the infarct
      (10% +/- 10, P < .0001) and the area at risk according to ESA (17% +/- 13, P <
      .0001). In six patients, no late contrast enhancement was seen, whereas all
      patients had an area of reduced FDG uptake (29% +/- 8) in the perfusion territory
      of the culprit artery. CONCLUSION: In patients with reperfused acute myocardial
      infarction, the area of reduced FDG uptake correlates with the area at risk as
      determined with the ESA method and is localized in the perfusion territory of the
      culprit artery in the absence of necrosis, although the area of reduced FDG
      uptake largely overestimates the size of the infarct and the ESA-based area at
      risk.

PMID- 25848896
TI  - Expression of surfactant protein D in airways of asthmatics and interleukin-13
      modulation of surfactant protein D in human models of airway epithelium.
AB  - BACKGROUND: Surfactant protein D (SP-D), a pattern recognition molecule, has been
      shown to play roles in host defense such as opsonisation, aggregation of
      pathogens, and modulation of the inflammatory response. In light of infection
      induced exacerbations and damage to the airway epithelium from inflammation,
      these functions of SP-D make it relevant in the development and pathogenesis of
      asthma. METHODS: Expression of SP-D was examined in human airway sections and
      primary airway epithelial cells (AEC) grown in air-liquid interface (ALI)
      cultures and comparisons were made between those from asthmatic and non-asthmatic
      donors. ALI cultures of AEC from non-asthmatic donors were examined for SP-D,
      Mucin 5AC, and cytokeratin-5 expression at different stages of differentiation.
      Interleukin-13 (IL-13) treatment of airway epithelium and its effect on SP-D
      expression was studied using ALI and monolayer cultures of primary AEC from non
      asthmatic and asthmatic donors. RESULTS: Airway epithelium of asthmatics,
      compared to that of non-asthmatics, expressed increased levels of SP-D as
      demonstrated in airway tissue sections (fraction of epithelium 0.66 +/- 0.026 vs.
      0.50 +/- 0.043, p = 0.004) and ALI cultures (fraction of epithelium 0.50 +/- 0.08
      vs. 0.25 +/- 0.07). SP-D expression decreased as ALI cultures differentiated from
      7 days to 21 days (fraction of epithelium 0.62 +/- 0.04 to 0.23 +/- 0.03, p =
      0.004). Treatment with IL-13 decreased SP-D expression in both ALI cultures
      (fraction of epithelium 0.21 +/- 0.06 vs. 0.62 +/- 0.04, p = 0.0005) and
      monolayer cultures (protein expression fold change 0.62 +/- 0.05) of non
      asthmatic AEC; however, IL-13 had no significant effect on SP-D expression in
      monolayer cultures of asthmatic AEC. Experiments with non-asthmatic monolayer
      cultures indicate IL-13 exert its effect on SP-D through the IL-13 receptor
      alpha1 and transcription factor STAT6. CONCLUSIONS: SP-D is expressed differently
      in airways of asthmatics relative to that of non-asthmatics. This can have
      implications on the increased susceptibility to infections and altered
      inflammatory response in asthmatic patients. Future functional studies on the
      role of SP-D in asthma can provide better insight into defects in the structure
      and regulation of SP-D.

PMID- 25848899
TI  - Reduced Radiation Dose with Model-based Iterative Reconstruction versus Standard
      Dose with Adaptive Statistical Iterative Reconstruction in Abdominal CT for
      Diagnosis of Acute Renal Colic.
AB  - PURPOSE: To evaluate the accuracy of reduced-dose abdominal computed tomographic
      (CT) imaging by using a new generation model-based iterative reconstruction
      (MBIR) to diagnose acute renal colic compared with a standard-dose abdominal CT
      with 50% adaptive statistical iterative reconstruction (ASIR). MATERIALS AND
      METHODS: This institutional review board-approved prospective study included 118
      patients with symptoms of acute renal colic who underwent the following two
      successive CT examinations: standard-dose ASIR 50% and reduced-dose MBIR. Two
      radiologists independently reviewed both CT examinations for presence or absence
      of renal calculi, differential diagnoses, and associated abnormalities. The
      imaging findings, radiation dose estimates, and image quality of the two CT
      reconstruction methods were compared. Concordance was evaluated by kappa
      coefficient, and descriptive statistics and t test were used for statistical
      analysis. RESULTS: Intraobserver correlation was 100% for the diagnosis of renal
      calculi (kappa = 1). Renal calculus (tau = 98.7%; kappa = 0.97) and obstructive
      upper urinary tract disease (tau = 98.16%; kappa = 0.95) were detected, and
      differential or alternative diagnosis was performed (tau = 98.87% kappa = 0.95).
      MBIR allowed a dose reduction of 84% versus standard-dose ASIR 50% (mean volume
      CT dose index, 1.7 mGy +/- 0.8 [standard deviation] vs 10.9 mGy +/- 4.6; mean
      size-specific dose estimate, 2.2 mGy +/- 0.7 vs 13.7 mGy +/- 3.9; P < .001)
      without a conspicuous deterioration in image quality (reduced-dose MBIR vs ASIR
      50% mean scores, 3.83 +/- 0.49 vs 3.92 +/- 0.27, respectively; P = .32) or
      increase in noise (reduced-dose MBIR vs ASIR 50% mean, respectively, 18.36 HU +/-
      2.53 vs 17.40 HU +/- 3.42). Its main drawback remains the long time required for
      reconstruction (mean, 40 minutes). CONCLUSION: A reduced-dose protocol with MBIR
      allowed a dose reduction of 84% without increasing noise and without an
      conspicuous deterioration in image quality in patients suspected of having renal
      colic.

PMID- 25848900
TI  - Prostate Cancer: The European Society of Urogenital Radiology Prostate Imaging
      Reporting and Data System Criteria for Predicting Extraprostatic Extension by
      Using 3-T Multiparametric MR Imaging.
AB  - PURPOSE: To retrospectively assess the use of the European Society of Urogenital
      Radiology (ESUR) Prostate Imaging Reporting and Data System (PI-RADS) criteria
      and 3-T multiparametric magnetic resonance (MR) imaging for detection of
      extraprostatic extension (EPE) of prostate cancer. MATERIALS AND METHODS: The
      institutional review board approval requirement was waived. Consecutive patients
      with prostate cancer (n = 133) underwent 3-T multiparametric MR imaging before
      prostatectomy. Lesions were assessed by using ESUR/PI-RADS criteria for T2
      weighted, diffusion-weighted, and dynamic contrast material-enhanced imaging, and
      by using the sum of these scores. Zonal dominant parameters corresponding to the
      score of diffusion-weighted imaging for peripheral zone lesions and to T2
      weighted imaging scores for transitional zone lesions were calculated. In
      addition, the presence of EPE in each patient was evaluated on the basis of
      subjective multiparametric MR imaging features. Histopathologic examination of
      whole-mount radical prostatectomy specimens was used as the reference standard.
      Sensitivity, specificity, positive predictive, and negative predictive values;
      likelihood ratios; and areas under the receiver operating characteristic curve
      were calculated for each parameter on the basis of its usefulness for prediction
      of EPE. RESULTS: EPE was found in 60 of 133 (45%) patients. Receiver operating
      characteristic curve analysis for the prediction of EPE revealed an area under
      the curve of 0.72 for T2-weighted, 0.67 for diffusion-weighted, and 0.64 for
      dynamic contrast-enhanced imaging; 0.74 for the dominant parameter; and 0.74 for
      the sum of the PI-RADS scores, and a score of 5 was defined as the best threshold
      for the individual parameters, with a score greater than or equal to 13 as the
      threshold for the sum of the PI-RADS scores. By applying these thresholds,
      sensitivity, negative predictive value, and negative likelihood ratio (ruling out
      EPE) were 77%, 77%, and 0.36, respectively, and specificity, positive predictive
      value, and positive likelihood ratio (ruling in EPE) were 64%, 64%, and 2.15,
      respectively, for the dominant parameter. Feature analysis showed an area under
      the curve of 0.72; sensitivity, negative predictive value, and negative
      likelihood ratio of 63%, 72%, and 0.56, respectively, and specificity, positive
      predictive value, and positive likelihood ratio of 78%, 70%, and 3.77,
      respectively. CONCLUSION: ESUR/PI-RADS criteria showed moderate overall accuracy
      for use in the prediction of EPE, and these results were similar to those of
      multiparametric MR imaging assessment of features in this study sample.

PMID- 25848901
TI  - Disrupted Functional Brain Connectome in Patients with Posttraumatic Stress
      Disorder.
AB  - PURPOSE: To use resting-state functional magnetic resonance (MR) imaging and
      graph theory approaches to systematically investigate the topological
      organization of the functional connectome of patients with posttraumatic stress
      disorder (PTSD). MATERIALS AND METHODS: This study was approved by the research
      ethics committee, and all subjects provided informed consent for participation.
      Seventy-six patients with PTSD caused by an earthquake and 76 control subjects
      who experienced the same disaster were matched for age, sex, and years of
      education. The study subjects underwent resting-state functional MR imaging. The
      whole-brain functional network was then constructed by thresholding partial
      correlation matrices of 90 brain regions. The topological organization of the
      constructed network was analyzed by using graph theory approaches. Nonparametric
      permutation tests were also used for group comparisons of topological metrics.
      RESULTS: Compared with the control subjects, patients with PTSD exhibited
      abnormalities in global properties, including a significant decrease in path
      length (P = .0002) and increases in the clustering coefficient (P = .0014),
      global efficiency (P = .0002), and local efficiency (P = .0004). Locally, the
      patients with PTSD exhibited increased centrality in nodes that are predominately
      involved in the default-mode network (DMN) and the salience network (SN),
      including the posterior cingulate gyrus, the precuneus, the insula, the putamen,
      the pallidum, and the temporal regions. CONCLUSION: These results suggest that
      individuals with PTSD exhibit a shift toward "small-worldization" (in which the
      network transforms from a random or regular network to a small-world network)
      rather than toward randomization; furthermore, the disequilibrium between the DMN
      and the SN might be associated with the pathophysiology of PTSD.

PMID- 25848902
TI  - Chronic Obstructive Pulmonary Disease: Pulmonary Function and CT Lung Attenuation
      Do Not Show Linear Correlation.
AB  - PURPOSE: To determine whether the relationship between pulmonary function and
      computed tomographic (CT) lung attenuation in chronic obstructive pulmonary
      disease (COPD), which is traditionally described with single univariate and
      multivariate statistical models, could be more accurately described with a
      multiple model estimation approach. MATERIALS AND METHODS: The study was approved
      by the local ethics committee. All participants provided written informed
      consent. The prediction of the percentage area with CT attenuation values less
      than -950 HU at inspiration (%LAA-950insp) and less than -910 HU at expiration
      (%LAA-910exp) obtained with single univariate and multivariate models was
      compared with that obtained with a multiple model estimation approach in 132
      patients with COPD. RESULTS: At univariate analysis, %LAA-950insp and %LAA-910exp
      values higher than the mean value of this cohort (19.1% and 22.0%) showed better
      correlation with percentage of predicted diffusing capacity of lung for carbon
      monoxide (Dlco%) than with airflow obstruction (forced expiratory volume in 1
      second [FEV1]/vital capacity [VC]). Conversely, %LAA-950insp and %LAA-910exp
      values lower than the mean value were correlated with FEV1/VC but not with Dlco%.
      Multiple model estimation performed with two multivariate regressions, each
      selecting the most appropriate functional variables (FEV1/VC for mild parenchymal
      destruction, Dlco% and functional residual capacity for severe parenchymal
      destruction), predicted better than single multivariate regression both %LAA
      950insp (R(2) = 0.75 vs 0.46) and %LAA-910exp (R(2) = 0.83 vs 0.63). CONCLUSION:
      The relationship between pulmonary function data and CT densitometric changes in
      COPD varies with the level of lung attenuation impairment. The nonlinear profile
      of this relationship is accurately predicted with a multiple model estimation
      approach.

PMID- 25848903
TI  - Determination of Single-Kidney Glomerular Filtration Rate in Human Subjects by
      Using CT.
AB  - PURPOSE: To test the hypothesis that computed tomography (CT)-derived
      measurements of single-kidney glomerular filtration rate (GFR) obtained in human
      subjects with 64-section CT agree with those obtained with iothalamate clearance,
      a rigorous reference standard. MATERIALS AND METHODS: The institutional review
      board approved this HIPAA-compliant study, and written informed consent was
      obtained. Ninety-six patients (age range, 51-73 years; 46 men, 50 women) with
      essential (n = 56) or renovascular (n = 40) hypertension were prospectively
      studied in controlled conditions (involving sodium intake and renin-angiotensin
      blockade). Single-kidney perfusion, volume, and GFR were measured by using
      multidetector CT time-attenuation curves and were compared with GFR measured by
      using iothalamate clearance, as assigned to the right and left kidney according
      to relative volumes. The reproducibility of CT GFR over a 3-month period (n = 21)
      was assessed in patients with renal artery stenosis who were undergoing stable
      medical treatment. Statistical analysis included the t test, Wilcoxon signed rank
      test, linear regression, and Bland-Altman analysis. RESULTS: CT GFR values were
      similar to those of iothalamate clearance (mean +/- standard deviation, 38.2
      mL/min +/- 18 vs 41.6 mL/min +/- 17; P = .062). Stenotic kidney CT GFR in
      patients with renal artery stenosis was lower than contralateral kidney GFR or
      essential hypertension single-kidney GFR (mean, 23.1 mL/min +/- 13 vs 36.9 mL/min
      +/- 17 [P = .0008] and 45.2 mL/min +/- 16 [P = .019], respectively), as was
      iothalamate clearance (mean, 26.9 mL/min +/- 14 vs 38.5 mL/min +/- 15 [P = .0004]
      and 49.0 mL/min +/- 14 [P = .001], respectively). CT GFR correlated well with
      iothalamate GFR (linear regression, CT GFR = 0.88*iothalamate GFR, r(2) = 0.89, P
      < .0001), and Bland-Altman analysis was used to confirm the agreement. CT GFR was
      also moderately reproducible in medically treated patients with renal artery
      stenosis (concordance coefficient correlation, 0.835) but was unaffected by
      revascularization (mean, 25.3 mL/min +/- 15.2 vs 30.3 mL/min +/- 18.5; P = .097).
      CONCLUSION: CT assessments of single-kidney GFR are reproducible and agree well
      with a reference standard. CT can be useful to obtain minimally invasive
      estimates of bilateral single-kidney function in human subjects.

PMID- 25848904
TI  - Thyroid Nodules: Nondiagnostic Cytologic Results according to Thyroid Imaging
      Reporting and Data System before and after Application of the Bethesda System.
AB  - PURPOSE: To compare the malignancy rates and the effectiveness of the Thyroid
      Imaging Reporting and Data System (TIRADS) for risk stratification of nodules
      with nondiagnostic results classified before and after application of the
      Bethesda System for Reporting Thyroid Cytopathology. MATERIALS AND METHODS: This
      retrospective study was approved by an institutional review board, with waiver of
      informed consent. A total of 763 patients with 790 thyroid nodules and
      nondiagnostic cytologic results were included (mean age +/- standard deviation,
      52.3 years +/- 11.5), 485 nodules from the pre-Bethesda period (from March 2007
      to December 2008) and 305 nodules from the post-Bethesda period (from May 2011 to
      May 2012). A TIRADS category was assigned to each thyroid nodule on the basis of
      the number of features that appeared suspicious for cancer at ultrasonography
      (US). Malignancy rates and TIRADS categories during the two periods were
      compared. Correlation between TIRADS category and malignancy risk between the two
      periods was evaluated and compared. RESULTS: The malignancy rates of nodules with
      nondiagnostic cytologic results were not significantly different between the two
      periods (P = .148). Malignancy risk of TIRADS category 3, 4a, 4b, 4c, and 5 was
      1.8%, 5.7%, 4.1%, 29.8%, and 16.7%, for the pre-Bethesda period, and 1.6%, 3.0%,
      7.1%, 16.3%, and 25.0% for the post-Bethesda period, respectively. Near-perfect
      correlation was seen between the TIRADS category and malignancy risk in the post
      Bethesda period (r = 0.961, P = .009), while no significant correlation was found
      in the pre-Bethesda period (r = 0.731, P = .161). CONCLUSION: Malignancy risk
      stratification with TIRADS was more effective for nodules with nondiagnostic
      cytologic results classified according to the Bethesda System. When these
      Bethesda-classified nodules with nondiagnostic results are evaluated as TIRADS
      category 3 or 4a, they may be treated conservatively with follow-up US, but when
      other cytologic classifications are applied, follow-up US and fine- needle
      aspiration must be considered for nodules showing one or more features suspicious
      for cancer at US.

PMID- 25848905
TI  - Gadolinium retention in the dentate nucleus and globus pallidus is dependent on
      the class of contrast agent.
AB  - PURPOSE: To compare changes in signal intensity (SI) ratios of the dentate
      nucleus (DN) and the globus pallidus (GP) to those of other structures on
      unenhanced T1-weighted magnetic resonance (MR) images between linear and
      macrocyclic gadolinium-based contrast agents (GBCAs). MATERIALS AND METHODS: The
      study was approved by the ethical committee of the University of Heidelberg
      (reference no. S-324/2014). Owing to the retrospective character of the study,
      the ethical committee did not require any written informed consent. Two groups of
      50 patients who underwent at least six consecutive MR imaging examinations with
      the exclusive use of either a linear GBCA (gadopentetate dimeglumine) or a
      macrocyclic GBCA (gadoterate meglumine) were analyzed retrospectively. The
      difference in mean SI ratios of DN to pons and GP to thalamus on unenhanced T1
      weighted images from the last and first examinations was calculated. One-sample
      and independent-sample t tests were used to assess the difference in SI ratios
      for both groups, and regression analysis was performed to account for potential
      confounders. RESULTS: The SI ratio difference in the linear group was greater
      than 0 (mean DN difference +/- standard deviation, 0.0407 +/- 0.0398 [P < .001];
      GP, 0.0287 +/- 0.0275 [P < .001]) and significantly larger (DN, P < .001 and
      standardized difference of 1.16; GP, P < .001 and standardized difference of
      0.81) than that in the macrocyclic group, which did not differ from 0 (DN, 0.0016
      +/- 0.0266 [P = .680]; GP, 0.0031 +/- 0.0354 [P = .538]). The SI ratio difference
      between the last and first examinations for the DN remained significantly
      different between the two groups in the regression analysis (P < .001).
      CONCLUSION: This study indicates that an SI increase in the DN and GP on T1
      weighted images is caused by serial application of the linear GBCA gadopentetate
      dimeglumine but not by the macrocyclic GBCA gadoterate meglumine. Clinical
      implications of this observation remain unclear.

PMID- 25848907
TI  - Histopathological Analysis of Internal Limiting Membrane Surgically Peeled From
      Eyes with Epiretinal Membrane.
AB  - PURPOSE: To investigate histopathological changes of internal limiting membrane
      (ILM) in patients with epiretinal membrane (ERM) Materials and Methods: Forty-two
      eyes of 42 patients who were diagnosed as ERM and enrolled for vitreoretinal
      surgery were included in this study. Brilliant Blue G (BBG) was used to stain the
      ILM in all patients. ILM was peeled in all subjects and analyzed by light
      microscopy (methylene blue-Azur II * 40). ILM samples were then fixed in 2.5%
      glutaraldehyde solution and examined in JEOL-JEM 1400 and 2100F electron
      microscope and photographed by CCD camera (Gatan Inc., Pleasanton, CA). RESULTS:
      Remained ERM fragments were observed on 80% of ILM's. Vacuolization of ILM was
      observed in a patient with diabetic ERM. There were cells and cellular fragments
      observed mostly at retinal side of ILM which was likely to be a fragment of
      Muller cells of retina. CONCLUSIONS: Most of the ILM's had residual ERM tissue
      and contained cells and cellular fragments at retinal side of ILM's. ILM peeling
      might have a role in decreasing ERM recurrence by removal of residual ERM
      tissues.

PMID- 25848906
TI  - Pleiotropic functions of the tumor- and metastasis-suppressing matrix
      metalloproteinase-8 in mammary cancer in MMTV-PyMT transgenic mice.
AB  - INTRODUCTION: Matrix metalloproteinase-8 (MMP-8; neutrophil collagenase) is an
      important regulator of innate immunity that has oncosuppressive actions in
      numerous tumor types. METHODS: We have intercrossed Mmp8-null mice with the
      Polyoma virus middle T oncogene-driven (MMTV-PyMT) mouse model of mammary cancer
      to explore the effects of loss of MMP-8 on the incidence and progression of
      mammary carcinomas. RESULTS: In this aggressive mouse model of breast cancer,
      loss of MMP-8 accelerated tumor onset even further, such that 90% of MMTV-PyMT;
      Mmp8-null female mice were tumor-bearing at the time of weaning. Throughout the
      14 weeks of the model, tumor burden increased in homozygous Mmp8-null mice
      compared to Mmp8-wild-type and -heterozygote animals. Likewise, lung metastasis
      dramatically increased in the MMTV-PyMT; Mmp8-null mice. Immunohistochemistry
      revealed that tumors in wild-type, Mmp8-heterozygotes and -null animals had
      similar vascular density at 8 weeks, but at 10 weeks Mmp8-wild-type tumors had a
      lower vascularity than their heterozygote and null counterparts. No differences
      in macrophage infiltration were apparent throughout primary tumor development,
      though at 10 weeks a drop in neutrophil infiltrates was observed in Mmp8-wild
      type tumors. Using quantitative real-time RT-PCR, we tracked the expression of
      the entire Mmp and Timp gene families, observing a significant decrease in Mmp3
      expression in Mmp8-null tumors compared to wild-type and heterozygotes throughout
      the time course of the model, which was confirmed at the protein level.
      CONCLUSIONS: These findings provide novel insight into the suppressive action of
      MMP-8 on mammary tumorigenesis and metastasis, and indicate that the loss of MMP
      8 likely has pleiotropic effects on innate immunity and angiogenesis that are
      reflected in changes in the protease web.

PMID- 25848908
TI  - Bacteremia in adult cancer patients with apparently stable febrile neutropenia:
      data from a cohort of 692 consecutive episodes from a single institution.
AB  - BACKGROUND: Bacteremia is associated with increased risk of complications in
      patients with febrile neutropenia (FN), although few clinical studies have
      reported outcomes in apparently stable patients (ASPs) who could be candidates
      for home treatment. OBJECTIVE: To assess the risk factors and the impact of
      bacteremia in ASPs. METHODS: We retrospectively analyzed 861 consecutive episodes
      of FN that were classifed according to their presentation into 2 categories:
      clearly unstable patients and ASPs. We estimated the incidence of bacteremia and
      severe complications in ASPs. We analyzed predictors for bacteremia and the
      discriminatory ability of the MASCC score in this setting. RESULTS: We classifed
      692 episodes as ASPs. Bacteremia occurred in 6%, major complications were noted
      in 7.3%, and death occurred in 1.3%. Patients with bacteremia had more
      complications (odds ratio [OR], 8.2), and mortality (OR, 8.2). The integration of
      the MASCC score and bacteremic status predicted complications with an area under
      the receiver operating characteristic (ROC) curve of 0.74, sensitivity of 36%,
      and specifcity of 94%. Predictors of bacteremia were temperature >= 39 degrees
      C/102.2 degrees F (OR, 3), rigors (OR, 2.2), ECOG PS >= 2 (OR, 2.1), and advanced
      cancer (OR, 2.5). Two percent of patients who remained afebrile for 48 hours had
      positive blood cultures afterward. LIMITATIONS: A single-center, retrospective
      analysis, and the absence of a validation set to test the model's discriminatory
      ability. CONCLUSIONS: Bacteremia is infrequent among ASPs but is associated with
      a high risk of complications. We identifed several variables that could improve
      the prognostic classifcation of clinically stable FN.

PMID- 25848909
TI  - Treatment patterns and clinical effectiveness in metastatic castrate resistant
      prostate cancer after first-line docetaxel.
AB  - BACKGROUND: Treatment for metastatic castrate-resistant prostate cancer in
      community settings is not well understood. OBJECTIVE: To examine treatment
      patterns, sequencing, and outcomes in patients receiving second- and third-line
      treatment after first-line docetaxel. METHODS: We used a community oncology
      database to identify patients who progressed after line 1 docetaxel (D) and
      received line 2 cabazitaxel (DC), abiraterone (DA), or other therapy (DO).
      Progression-free survival (PFS) and overall survival (OS) were assessed using
      Kaplan- Meier and Cox regression models. Line 3 included subsets DCA and DAC.
      RESULTS: Line 2 groups (DC = 60 patients, DA = 71, DO = 153) did not differ
      significantly on demographic and clinical characteristics or median PFS on
      docetaxel therapy. Cox regression for OS by line 2 groups showed increased risk
      for DA compared with DC (HR, 1.69; P = .026) when 24 untreated DO patients were
      excluded. A similar nonsignificant pattern was observed when the 24 untreated
      patients were included. Of patients receiving DC in line 2, a nominally greater
      proportion received A in line 3 (57%, 34 of 60 patients) than did patients who
      received DA in line 2 followed by C in line 3 (25%, 18 of 71). LIMITATIONS: There
      was a small sample for line 3, and unexamined confounds and selection biases in
      observational research. Conclusions Treatment patterns in community settings
      following docetaxel are complex and may involve multiple hormonal agents prior to
      disease progression. Cabazitaxel may not be optimally used in advanced disease.
      Although Cox regression showed increased risk of death for DA compared with DC,
      results need to be validated prospectively. CONCLUSIONS: Treatment patterns in
      community settings following docetaxel are complex and may involve multiple
      hormonal agents prior to disease progression. Cabazitaxel may not be optimally
      used in advanced disease. Although Cox regression showed increased risk of death
      for DA compared with DC, results need to be validated prospectively.

PMID- 25848910
TI  - Metastic melanoma masquerading as disseminated sporotrichosis.
AB  - A 66-year-old man presented with diffuse slate-gray skin discoloration and
      multiorgan failure. Diagnostic workup showed disseminated bone and visceral
      lesions and positive Sporothrix serology. He was treated with antifungals for
      disseminated sporotrichosis but he died shortly after. Autopsy revealed
      metastatic melanoma with diffuse melanosis and no Sporothrix infection. 

PMID- 25848911
TI  - Atomically mixed Fe-group nanoalloys: catalyst design for the selective
      electrooxidation of ethylene glycol to oxalic acid.
AB  - We demonstrate electric power generation via the electrooxidation of ethylene
      glycol (EG) on a series of Fe-group nanoalloy (NA) catalysts in alkaline media. A
      series of Fe-group binary NA catalysts supported on carbon (FeCo/C, FeNi/C, and
      CoNi/C) and monometallic analogues (Fe/C, Co/C, and Ni/C) were synthesized.
      Catalytic activities and product distributions on the prepared Fe-group NA
      catalysts in the EG electrooxidation were investigated by cyclic voltammetry and
      chronoamperometry, and compared with those of the previously reported FeCoNi/C,
      which clarified the contributory factors of the metal components for the EG
      electrooxidation activity, C2 product selectivity, and catalyst durability. The
      Co-containing catalysts, such as Co/C, FeCo/C, and FeCoNi/C, exhibit relatively
      high catalytic activities for EG electrooxidation, whereas the catalytic
      performances of Ni-containing catalysts are relatively low. However, we found
      that the inclusion of Ni is a requisite for the prevention of rapid degradation
      due to surface modification of the catalyst. Notably, FeCoNi/C shows the highest
      selectivity for oxalic acid production without CO2 generation at 0.4 V vs. the
      reversible hydrogen electrode (RHE), resulting from the synergetic contribution
      of all of the component elements. Finally, we performed power generation using
      the direct EG alkaline fuel cell in the presence of the Fe-group catalysts. The
      power density obtained on each catalyst directly reflected the catalytic
      performances elucidated in the electrochemical experiments for the corresponding
      catalyst. The catalytic roles and alloying effects disclosed herein provide
      information on the design of highly efficient electrocatalysts containing Fe
      group metals.

PMID- 25848913
TI  - Markers for the identification of late breast cancer recurrence.
AB  - Postmenopausal women with early breast cancer are at an ongoing risk of relapse,
      even after successful surgery and treatment of the primary tumor. The treatment
      of breast cancer has changed in the past few years because of the discovery of
      prognostic and predictive biomarkers that allow individualized breast cancer
      treatment. However, it is still not clear how to identify women that are at high
      risk of a late recurrence. Clinical parameters are good prognostic markers for
      early recurrence, but only nodal status and, to a lesser extent, tumor size have
      proven to be strong prognostic markers for late recurrence. Multi-gene signatures
      have become widely used for the prediction of overall recurrence risk and
      tailoring administration of adjuvant chemotherapy, but only a few have been shown
      to be prognostic for late (distant) relapse. There is a need to accurately
      identify women who may benefit from extended endocrine therapy but also those who
      may be spared any additional treatment. Recent results from large clinical trials
      have shown that the research is going in the right direction, and these results
      might help to optimize extended endocrine therapy for patients with early breast
      cancer. However, further research is needed to select individual biomarkers or
      multi-gene signatures that offer identification of late recurrence specifically
      and thus justify routine use of these tests in the clinical setting. 

PMID- 25848914
TI  - Localization and functional characterization of the extrinsic subunits of
      photosystem II: an update.
AB  - Photosystem II (PSII), which catalyzes photosynthetic water oxidation, is
      composed of more than 20 subunits, including membrane-intrinsic and -extrinsic
      proteins. The extrinsic proteins of PSII shield the catalytic Mn4CaO5 cluster
      from exogenous reductants and serve to optimize oxygen evolution at physiological
      ionic conditions. These proteins include PsbO, found in all oxygenic organisms,
      PsbP and PsbQ, specific to higher plants and green algae, and PsbU, PsbV, CyanoQ,
      and CyanoP in cyanobacteria. Furthermore, red algal PSII has PsbQ' in addition to
      PsbO, PsbV, and PsbU, and diatoms have Psb31 in supplement to red algal-type
      extrinsic proteins, exemplifying the functional divergence of these proteins
      during evolution. This review provides an updated summary of recent findings on
      PSII extrinsic proteins and discusses their binding, function, and evolution
      within various photosynthetic organisms.

PMID- 25848912
TI  - Plasma levels of matrix metalloproteinase-2, -3, -10, and tissue inhibitor of
      metalloproteinase-1 are associated with vascular complications in patients with
      type 1 diabetes: the EURODIAB Prospective Complications Study.
AB  - BACKGROUND: Impaired regulation of extracellular matrix remodeling by matrix
      metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase (TIMP) may
      contribute to vascular complications in patients with type 1 diabetes. We
      investigated associations between plasma MMP-1, -2, -3, -9, -10 and TIMP-1, and
      cardiovascular disease (CVD) or microvascular complications in type 1 diabetic
      patients. We also evaluated to which extent these associations could be explained
      by low-grade inflammation (LGI) or endothelial dysfunction (ED). METHODS: 493
      type 1 diabetes patients (39.5 +/- 9.9 years old, 51% men) from the EURODIAB
      Prospective Complications Study were included. Linear regression analysis was
      applied to investigate differences in plasma levels of MMP-1, -2, -3, -9, -10,
      and TIMP-1 between patients with and without CVD, albuminuria or retinopathy. All
      analyses were adjusted for age, sex, duration of diabetes, Hba1c and additionally
      for other cardiovascular risk factors including LGI and ED. RESULTS: Patients
      with CVD (n = 118) showed significantly higher levels of TIMP-1 [beta = 0.32 SD
      (95%CI: 0.12; 0.52)], but not of MMPs, than patients without CVD (n = 375).
      Higher plasma levels of MMP-2, MMP-3, MMP-10 and TIMP-1 were associated with
      higher levels of albuminuria (p-trends were 0.028, 0.004, 0.005 and 0.001,
      respectively). Severity of retinopathy was significantly associated with higher
      levels of MMP-2 (p-trend = 0.017). These associations remained significant after
      further adjustment for markers of LGI and ED. CONCLUSIONS: These data support the
      hypothesis that impaired regulation of matrix remodeling by actions of MMP-2, -3
      and-10 and TIMP-1 contributes to the pathogenesis of vascular complications in
      type 1 diabetes.

PMID- 25848916
TI  - Accumulation of Metals and Boron in Phragmites australis Planted in Constructed
      Wetlands Polishing Real Electroplating Wastewater.
AB  - The concentration of metals (Al, Cu, Fe, Mn, Ni, Zn) and B were determined in the
      above- and belowground biomass of Phragmites australis collected from the
      microcosm constructed wetland system used for the polishing of real
      electroplating wastewater. Translocation factor and bioconcentration factor were
      determined. Pearson correlation test was used to determine correlation between
      metal concentration in substrate and above- and belowground parts of Phragmites
      australis. The obtained results suggested that Phragmites australis did not play
      a major role as an accumulator of metals. It was observed also that the substrate
      could have exerted an effect on the translocation of Ni, Cu, Zn and Mn. The
      analysed concentrations of metals and B in biomass were in the range or even
      below the concentrations reported in the literature with the exception of Ni. The
      aboveground biomass was found suitable as a composting input in terms of metals
      concentrations. 

PMID- 25848915
TI  - Combined histone deacetylase inhibition and tamoxifen induces apoptosis in
      tamoxifen-resistant breast cancer models, by reversing Bcl-2 overexpression.
AB  - INTRODUCTION: The emergence of hormone therapy resistance, despite continued
      expression of the estrogen receptor (ER), is a major challenge to curing breast
      cancer. Recent clinical studies suggest that epigenetic modulation by histone
      deacetylase (HDAC) inhibitors reverses hormone therapy resistance. However,
      little is known about epigenetic modulation of the ER during acquired hormone
      resistance. Our recent phase II study demonstrated that HDAC inhibitors re
      sensitize hormone therapy-resistant tumors to the anti-estrogen tamoxifen. In
      this study, we sought to understand the mechanism behind the efficacy of this
      combination. METHODS: We generated cell lines resistant to tamoxifen, named TAMRM
      and TAMRT, by continuous exposure of ER-positive MCF7 and T47D cells,
      respectively to 4-hydroxy tamoxifen for over 12 months. HDAC inhibition, along
      with pharmacological and genetic manipulation of key survival pathways, including
      ER and Bcl-2, were used to characterize these resistant models. RESULTS: The
      TAMRM cells displayed decreased sensitivity to tamoxifen, fulvestrant and
      estrogen deprivation. Consistent with previous models, ER expression was retained
      and the gene harbored no mutations. Compared to parental MCF7 cells, ER
      expression in TAMRM was elevated, while progesterone receptor (PGR) was lost.
      Sensitivity of ER to ligands was greatly reduced and classic ER response genes
      were suppressed. This model conveyed tamoxifen resistance through transcriptional
      upregulation of Bcl-2 and c-Myc, and downregulation of the cell cycle checkpoint
      protein p21, manifesting in accelerated growth and reduced cell death. Similar to
      TAMRM cells, the TAMRT cell line exhibited substantially decreased tamoxifen
      sensitivity, increased ER and Bcl-2 expression and significantly reduced PGR
      expression. Treatment with HDAC inhibitors reversed the altered transcriptional
      events and reestablished the sensitivity of the ER to tamoxifen resulting in
      substantial Bcl-2 downregulation, growth arrest and apoptosis. Selective
      inhibition of Bcl-2 mirrored these effects in presence of an HDAC inhibitor.
      CONCLUSIONS: Our model implicates elevated ER and Bcl-2 as key drivers of anti
      estrogen resistance, which can be reversed by epigenetic modulation through HDAC
      inhibition.

PMID- 25848917
TI  - Detection of survival motor neuron protein in buccal cells through
      electrochemiluminescence-based assay.
AB  - Spinal muscular atrophy (SMA) is a severe autosomal recessive disorder affecting
      one in every 10,000 live births. The disease is characterized by loss of alpha
      motor neurons in the spinal cord that leads to progressive atrophy and weakness
      of limb and trunk muscles. This neuromuscular disorder results from deletions
      and/or mutations within the survival motor neuron 1 (SMN1) gene, leading to a
      pathologically decreased expression of functional full-length SMN protein. Here
      we report on the investigation to measure SMN protein levels through
      electrochemiluminescence immunoassay (ECLIA). This simple assay is a highly
      quantitative method able to measure SMN protein levels in human, mouse, and rat
      samples throughout a wide working range with low intra- and interassay error. The
      sensitivity for human SMN is 30 pg/mL and provides a new tool for the set up of
      high-throughput screening for basic research. Moreover, we describe a novel tool
      for a noninvasive assessment of SMN in buccal cells derived from healthy donors,
      SMA carriers, and SMA patients. The availability of a validated quantitative
      ECLIA should improve the investigation of novel compounds for the treatment of
      SMA.

PMID- 25848919
TI  - Controlling the fluorescence behavior of 1-pyrenesulfonate by cointercalation
      with a surfactant in a layered double hydroxide.
AB  - Zn-Al layered double hydroxides (LDHs) containing solely 1-pyrenesulfonate (PS)
      or 1-heptanesulfonate (HS) anions, or a mixture of the two with HS/PS molar
      ratios ranging between ca. 7.5 and 82, were prepared by the direct synthesis
      method and characterized by powder X-ray diffraction, thermal and elemental
      analyses, scanning electron microscopy, and FT-IR, FT-Raman, and (13)C{(1)H} CP
      MAS NMR spectroscopies. Well-ordered intercalates were obtained with basal
      spacings of 18.8 A for the LDH intercalated by PS and 19.2-19.4 A for the other
      materials containing HS. The photophysics of the solids, as well as the PS probe
      dissolved in water and common organic solvents (aiming to compare the behavior of
      the "isolated" molecule with that in the solid), were investigated by steady
      state and time-resolved fluorescence techniques. The fluorescence spectra of the
      solid samples display two bands with maxima at 376 and 495 nm. Depending on the
      HS/PS ratios, the band intensity ratio (obtained at 375 and 520 nm) changes,
      reflecting different contributions from monomer and dimer species. The decays
      collected at 375 nm are biexponentials with a major component (~97% of the total
      fluorescence) of 105 ns for the highest HS/PS ratio, which further loses
      importance with an increase in the PS content. When the decays are collected at
      480 and 520 nm, the fits are triexponentials with a major component varying from
      108 to 124 ns, attributed to an excimer. Steady-state and time-resolved
      measurements with PS in solution (ethanol, methanol, DMF, DMSO, and water) were
      also measured, and a comparison of the vibronic I1/I3 ratio and lifetimes in
      water (65 ns) with those in the LDHs indicates that the PS probe in the
      cointercalated LDHs is surrounded by the HS surfactant. 

PMID- 25848918
TI  - Nitroxoline impairs tumor progression in vitro and in vivo by regulating
      cathepsin B activity.
AB  - Cathepsin B is a ubiquitously expressed lysosomal cysteine protease that
      participates in protein turnover within lysosomes. However, its protein and
      activity levels have been shown to be increased in cancer. Cathepsin B
      endopeptidase activity is involved in the degradation of extracellular matrix, a
      process that promotes tumor invasion, metastasis and angiogenesis. Previously, we
      reported an established antibiotic nitroxoline as a potent and selective
      inhibitor of cathepsin B. In the present study, we elucidated its anti-tumor
      properties in in vitro and in vivo tumor models. Tumor and endothelial cell lines
      with high levels of active cathepsin B were selected for functional analysis of
      nitroxoline in vitro. Nitroxoline significantly reduced extracellular DQ-collagen
      IV degradation by all evaluated cancer cell lines using spectrofluorimetry.
      Nitroxoline also markedly decreased tumor cell invasion monitored in real time
      and reduced the invasive growth of multicellular tumor spheroids, used as a 3D in
      vitro model of tumor invasion. Additionally, endothelial tube formation was
      significantly reduced by nitroxoline in an in vitro angiogenesis assay. Finally,
      nitroxoline significantly abrogated tumor growth, angiogenesis and metastasis in
      vivo in LPB fibrosarcoma and MMTV-PyMT breast cancer mouse models. Overall, our
      results designate nitroxoline as a promising drug candidate for anti-cancer
      treatment. 

PMID- 25848920
TI  - Sandwich-structured nanohybrid paper based on controllable growth of
      nanostructured MnO2 on ionic liquid functionalized graphene paper as a flexible
      supercapacitor electrode.
AB  - A sandwich-structured flexible supercapacitor electrode has been developed based
      on MnO2 nanonest (MNN) modified ionic liquid (IL) functionalized graphene paper
      (GP), which is fabricated by functionalizing graphene nanosheets with an amine
      terminated IL (i.e., 1-(3-aminopropyl)-3-methylimidazolium bromide) to form
      freestanding IL functionalized GP (IL-GP), and then modifying IL-GP with a unique
      MNN structure via controllable template-free ultrasonic electrodeposition. The as
      obtained MNN modified IL-GP (MNN/IL-GP) inherits the excellent pseudocapacity of
      the metal oxide, the high conductivity and electric double layer
      charging/discharging of IL-graphene composites, and therefore shows an enhanced
      supercapacitor performance. The maximum specific capacitance of 411 F g(-1) can
      be achieved by chronopotentiometry at a current density of 1 A g(-1). Meanwhile,
      the MNN/IL-GP electrode exhibits excellent rate capability and cycling stability,
      its specific capacitance is maintained at 70% as the current densities increase
      from 1 to 20 A g(-1) and 85% at a current density of 10 A g(-1) after 10 000
      cycles. More importantly, the MNN/IL-GP displays distinguished mechanical
      stability and flexibility for device packaging, although its thickness is merely
      8 MUm. These features collectively demonstrate the potential of MNN/IL-GP as a
      high-performance paper electrode for flexible and lightweight and highly
      efficient electrochemical capacitor applications. 

PMID- 25848921
TI  - Motor neuron disease: loss-of-function mutations in TBK1 can cause familial ALS.

PMID- 25848922
TI  - Stroke: more than meets the eye--big consequences of small strokes.
AB  - A long-term outcome analysis in patients with lacunar stroke enrolled in the
      Secondary Prevention of Small Subcortical Strokes trial highlights the relevance
      of functional disability after small-vessel strokes. These data support the
      emerging 'burden of disease' concept in individuals with cerebral
      microangiopathy, and the role of MRI in outcome prediction.

PMID- 25848924
TI  - Using a Treat-to-Target Management Strategy to Improve the Doctor-Patient
      Relationship in Inflammatory Bowel Disease.
AB  - The doctor-patient relationship (DPR) in inflammatory bowel disease (IBD) has
      been facing new challenges, in part due to the substantial progress in medical
      and surgical management and also due to the rapid expansion of patient access to
      medical information. Not surprisingly, the complexity of IBD care and
      heterogeneity of the disease types may lead to conflict between a physician's
      therapeutic recommendations and the patient's wishes. In this commentary, we
      propose that the so-called "treat-to-target" approach of objective targets of
      disease control and serial adjustments to therapies can also strengthen the DPR
      in IBD by enabling defined trials of alternative approaches, followed by a more
      objective assessment and reconsideration of treatments. We contend that such
      respect for patient autonomy and the use of objective markers of disease activity
      improves the DPR by fostering trust and both engaging and empowering patients and
      physicians with the information necessary to make shared decisions about
      therapies. 

PMID- 25848923
TI  - Stimulation mapping of white matter tracts to study brain functional
      connectivity.
AB  - Despite advances in the new science of connectomics, which aims to
      comprehensively map neural connections at both structural and functional levels,
      techniques to directly study the function of white matter tracts in vivo in
      humans have proved elusive. Direct electrical stimulation (DES) mapping of the
      subcortical fibres offers a unique opportunity to investigate the functional
      connectivity of the brain. This original method permits real-time anatomo
      functional correlations, especially with regard to neural pathways, in awake
      patients undergoing brain surgery. In this article, the goal is to review new
      insights, gained from axonal DES, into the functional connectivity underlying the
      sensorimotor, visuospatial, language and sociocognitive systems. Interactions
      between these neural networks and multimodal systems, such as working memory,
      attention, executive functions and consciousness, can also be investigated by
      axonal stimulation. In this networking model of conation and cognition, brain
      processing is not conceived as the sum of several subfunctions, but results from
      the integration and potentiation of parallel-though partially overlapping
      subnetworks. This hodotopical account, supported by axonal DES, improves our
      understanding of neuroplasticity and its limitations. The clinical implications
      of this paradigmatic shift from localizationism to hodotopy, in the context of
      brain surgery, neurology, neurorehabilitation and psychiatry, are discussed. 

PMID- 25848925
TI  - The economic impact of Clostridium difficile infection: a systematic review.
AB  - OBJECTIVES: With Clostridium difficile infection (CDI) on the rise, knowledge of
      the current economic burden of CDI can inform decisions on interventions related
      to CDI. We systematically reviewed CDI cost-of-illness (COI) studies. METHODS: We
      performed literature searches in six databases: MEDLINE, Embase, the Health
      Technology Assessment Database, the National Health Service Economic Evaluation
      Database, the Cost-Effectiveness Analysis Registry, and EconLit. We also searched
      gray literature and conducted reference list searches. Two reviewers screened
      articles independently. One reviewer abstracted data and assessed quality using a
      modified guideline for economic evaluations. The second reviewer validated the
      abstraction and assessment. RESULTS: We identified 45 COI studies between 1988
      and June 2014. Most (84%) of the studies were from the United States, calculating
      costs of hospital stays (87%), and focusing on direct costs (100%). Attributable
      mean CDI costs ranged from $8,911 to $30,049 for hospitalized patients. Few
      studies stated resource quantification methods (0%), an epidemiological approach
      (0%), or a justified study perspective (16%) in their cost analyses. In addition,
      few studies conducted sensitivity analyses (7%). CONCLUSIONS: Forty-five COI
      studies quantified and confirmed the economic impact of CDI. Costing methods
      across studies were heterogeneous. Future studies should follow standard COI
      methodology, expand study perspectives (e.g., patient), and explore populations
      least studied (e.g., community-acquired CDI).

PMID- 25848926
TI  - Local recurrence after endoscopic resection for large colorectal neoplasia: a
      multicenter prospective study in Japan.
AB  - OBJECTIVES: Conventional endoscopic resection (CER) is a widely accepted
      treatment for early colorectal neoplasia; however, large colorectal neoplasias
      remain problematic, as they necessitate piecemeal resection, increasing the risk
      of local recurrence. Endoscopic submucosal dissection (ESD) can improve the en
      bloc resection rate. This study aimed to evaluate local recurrence and its
      associated risk factors after endoscopic resection (ER) for colorectal neoplasias
      >=20 mm. METHODS: A multicenter prospective study at 18 medium- and high-volume
      specialized institutions was conducted in Japan. Follow-up colonoscopy was
      performed after 12 months in cases of complete resection and after 3-6 months in
      cases of incomplete resection. Local recurrence was confirmed by endoscopic
      findings and/or pathological analysis. RESULTS: Follow-up colonoscopy was
      performed in 1,524 of 1,845 enrolled colorectal neoplasias (mean age, 65 years;
      885 men; median tumor size, 32.8 mm). The local recurrence rates were 4.3%
      (65/1,524), 6.8% (55/808), and 1.4% (10/716) for the entire cohort, for CER, and
      for ESD, respectively. The relative risks of local recurrence were 0.21 (95%
      confidence interval, 0.11-0.39) with ESD compared with CER, 0.32 (95% confidence
      interval, 0.11-0.92) with en bloc ESD compared with en bloc CER, and 0.90 (95%
      confidence interval, 0.39-2.12) with piecemeal ESD compared with piecemeal CER.
      Significant factors associated with local recurrence were piecemeal resection,
      laterally spreading tumors of granular type, tumor size >=40 mm, no pre-treatment
      magnification, and <=10 years of experience in CER, and piecemeal resection only
      in ESD. CONCLUSIONS: En bloc ESD reduces the local recurrence rate for large
      colorectal neoplasias. Piecemeal resection is the most important risk factor for
      local recurrence regardless of the ER method used.

PMID- 25848927
TI  - Injection Drug Use and Hepatitis C as Risk Factors for Mortality in HIV-Infected
      Individuals: The Antiretroviral Therapy Cohort Collaboration.
AB  - BACKGROUND: HIV-infected individuals with a history of transmission through
      injection drug use (IDU) have poorer survival than other risk groups. The extent
      to which higher rates of hepatitis C (HCV) infection in IDU explain survival
      differences is unclear. METHODS: Adults who started antiretroviral therapy
      between 2000 and 2009 in 16 European and North American cohorts with >70%
      complete data on HCV status were followed for 3 years. We estimated unadjusted
      and adjusted (for age, sex, baseline CD4 count and HIV-1 RNA, AIDS diagnosis
      before antiretroviral therapy, and stratified by cohort) mortality hazard ratios
      for IDU (versus non-IDU) and for HCV-infected (versus HCV uninfected). RESULTS:
      Of 32,703 patients, 3374 (10%) were IDU; 4630 (14%) were HCV+; 1116 (3.4%) died.
      Mortality was higher in IDU compared with non-IDU [adjusted HR 2.71; 95%
      confidence interval (CI): 2.32 to 3.16] and in HCV+ compared with HCV- (adjusted
      HR 2.65; 95% CI: 2.31 to 3.04). The effect of IDU was substantially attenuated
      (adjusted HR 1.57; 95% CI: 1.27 to 1.94) after adjustment for HCV, while
      attenuation of the effect of HCV was less substantial (adjusted HR 2.04; 95% CI:
      1.68 to 2.47) after adjustment for IDU. Both IDU and HCV were strongly associated
      with liver-related mortality (adjusted HR 10.89; 95% CI: 6.47 to 18.3 for IDU and
      adjusted HR 14.0; 95% CI: 8.05 to 24.5 for HCV) with greater attenuation of the
      effect of IDU (adjusted HR 2.43; 95% CI: 1.24 to 4.78) than for HCV (adjusted HR
      7.97; 95% CI: 3.83 to 16.6). Rates of CNS, respiratory and violent deaths
      remained elevated in IDU after adjustment for HCV. CONCLUSIONS: A substantial
      proportion of the excess mortality in HIV-infected IDU is explained by HCV
      coinfection. These findings underscore the potential impact on mortality of new
      treatments for HCV in HIV-infected people.

PMID- 25848928
TI  - Trace elements in Thunnus thynnus from Mediterranean Sea and benefit-risk
      assessment for consumers.
AB  - Trace elemental levels were determined by inductively coupled plasma-mass
      spectrometry in muscle, eggs and sperm of 23 Thunnus thynnus fishes collected
      from May to August 2013 in the Mediterranean Sea. Zn, Mn, Fe, Cu, Cr, Ni and Se
      content was compared with Recommended Daily Allowances. Cd, Hg and Pb
      concentrations were below the maximum limits fixed by the European Legislation.
      Tuna food safety was evaluated considering Tolerable Weekly Intake (TWI) or
      Provisional Tolerable Weekly Intake for As, Hg, Cd and Pb. Only BMDL01 data for
      As and Pb were calculated as established by the Joint FAO/WHO Expert Committed on
      Food Additives. The daily consumption of fresh tuna ensures a good intake of
      these elements. None of the tested samples surpassed the European maximum limits.
      Cd, Hg and Pb remained within safety margins, while As is slightly higher than
      the provisional TWI. 

PMID- 25848930
TI  - Small molecule-triggered Cas9 protein with improved genome-editing specificity.
AB  - Directly modulating the activity of genome-editing proteins has the potential to
      increase their specificity by reducing activity following target locus
      modification. We developed Cas9 nucleases that are activated by the presence of a
      cell-permeable small molecule by inserting an evolved 4-hydroxytamoxifen
      responsive intein at specific positions in Cas9. In human cells, conditionally
      active Cas9s modify target genomic sites with up to 25-fold higher specificity
      than wild-type Cas9. 

PMID- 25848932
TI  - Natural radioactivity and radiation hazards assessment of soil samples from the
      area of Tuzla and Lukavac, Bosnia and Herzegovina.
AB  - The results of activity concentration measurements of natural occurring
      radioactive nuclides (238)U, (235)U, (232)Th, (226)Ra, and (40)K in surface soil
      samples collected in the area of cities Tuzla and Lukavac, northeast region of
      Bosnia and Herzegovina were presented. Soil sampling was conducted at the
      localities that are situated in the vicinity of industrial zones of these cities.
      The measured activity was in the range from (8 +/- 4) to (95 +/- 28) Bq kg(-1)
      for (238)U, from (0.41 +/- 0.06) to (4.6 +/- 0.7) Bq kg(-1) for (235)U, from (7
      +/- 1) to (66 +/- 7) Bq kg(-1) for (232)Th, from (6 +/- 1) to (55 +/- 6) Bq kg(
      1) for (226)Ra, and from (83 +/- 12) to (546 +/- 55) Bq kg(-1) for (40)K. In
      order to evaluate the radiological hazard of the natural radioactivity for people
      living near industrial zones, the absorbed dose rate, the annual effective dose
      and the radium equivalent activity have been calculated and compared with the
      internationally approved values.

PMID- 25848929
TI  - Specific pools of endogenous peptides are present in gametophore, protonema, and
      protoplast cells of the moss Physcomitrella patens.
AB  - BACKGROUND: Protein degradation is a basic cell process that operates in general
      protein turnover or to produce bioactive peptides. However, very little is known
      about the qualitative and quantitative composition of a plant cell peptidome, the
      actual result of this degradation. In this study we comprehensively analyzed a
      plant cell peptidome and systematically analyzed the peptide generation process.
      RESULTS: We thoroughly analyzed native peptide pools of Physcomitrella patens
      moss in two developmental stages as well as in protoplasts. Peptidomic analysis
      was supplemented by transcriptional profiling and quantitative analysis of
      precursor proteins. In total, over 20,000 unique endogenous peptides, ranging in
      size from 5 to 78 amino acid residues, were identified. We showed that in both
      the protonema and protoplast states, plastid proteins served as the main source
      of peptides and that their major fraction formed outside of chloroplasts.
      However, in general, the composition of peptide pools was very different between
      these cell types. In gametophores, stress-related proteins, e.g., late
      embryogenesis abundant proteins, were among the most productive precursors. The
      Driselase-mediated protonema conversion to protoplasts led to a peptide
      generation "burst", with a several-fold increase in the number of components in
      the latter. Degradation of plastid proteins in protoplasts was accompanied by
      suppression of photosynthetic activity. CONCLUSION: We suggest that peptide pools
      in plant cells are not merely a product of waste protein degradation, but may
      serve as important functional components for plant metabolism. We assume that the
      peptide "burst" is a form of biotic stress response that might produce peptides
      with antimicrobial activity from originally functional proteins. Potential
      functions of peptides in different developmental stages are discussed.

PMID- 25848933
TI  - Resveratrol Fails to Extend Life Span in the Mosquito Anopheles stephensi.
AB  - Resveratrol, a plant polyphenol present in grape skins, has been theorized to
      account for the "French Paradox" by explaining how red wine may decrease the
      health risks associated with unhealthy diets. Resveratrol has been reported to
      extend life span in several different species. Other studies, however, have
      failed to find a resveratrol-induced life span effect. A recent meta-study
      analyzing previously published survival data concluded that, although resveratrol
      reliably and reproducibly extends life span in some species, its life span
      effects show diminished reliability in other organisms. The data are mixed, and
      it remains unclear how evolutionarily conserved resveratrol's effects on life
      span are. To gain further insight into this controversy, we studied the effects
      of various concentrations (200 MUM, 100 MUM, 50 MUM, or 0 MUM) of orally fed
      resveratrol on the life span of the mosquito Anopheles stephensi, an important
      vector of human malaria, under two different feeding treatments--sugar-fed only
      or sugar-fed with intermittent blood meals. Each treatment was repeated three
      times and both survivorship and mortality rates were analyzed for each replicate.
      For the majority of experiments, resveratrol failed to mediate a statistically
      significant effect on life span. Although there was one instance where
      resveratrol significantly increased life span, there were five other instances
      where resveratrol significantly decreased life span. We conclude from these data
      that, under normal conditions, resveratrol does not extend life span in A.
      stephensi.

PMID- 25848934
TI  - The Gender of "Energy": Language, Social Theory, and Cultural Change in Women's
      Lands in the United States.
AB  - Within women's intentional communities, women use the phrase women's energy to
      describe certain social interactions, a sense of community, and ideas about how
      gender is done or performed. For example, energy can express both difference in
      communication style between men and women and male dominance in social
      situations. During my fieldwork in these communities, I explored how this phrase
      suggests a reference to a precultural female body, but it is also sometimes used
      to explicitly reject biological reasons for gender difference. The term is easily
      understandable to a wide range of women from varying class backgrounds and
      encompasses both the unconscious side of social interactions and a possibility
      for future change. 

PMID- 25848931
TI  - siRNA screen identifies QPCT as a druggable target for Huntington's disease.
AB  - Huntington's disease (HD) is a currently incurable neurodegenerative condition
      caused by an abnormally expanded polyglutamine tract in huntingtin (HTT). We
      identified new modifiers of mutant HTT toxicity by performing a large-scale
      'druggable genome' siRNA screen in human cultured cells, followed by hit
      validation in Drosophila. We focused on glutaminyl cyclase (QPCT), which had one
      of the strongest effects on mutant HTT-induced toxicity and aggregation in the
      cell-based siRNA screen and also rescued these phenotypes in Drosophila. We found
      that QPCT inhibition induced the levels of the molecular chaperone alphaB
      crystallin and reduced the aggregation of diverse proteins. We generated new QPCT
      inhibitors using in silico methods followed by in vitro screening, which rescued
      the HD-related phenotypes in cell, Drosophila and zebrafish HD models. Our data
      reveal a new HD druggable target affecting mutant HTT aggregation and provide
      proof of principle for a discovery pipeline from druggable genome screen to drug
      development. 

PMID- 25848935
TI  - Probiotics, prebiotics, and microencapsulation: A review.
AB  - The development of a suitable technology for the production of probiotics is a
      key research for industrial production, which should take into account the
      viability and the stability of the organisms involved. Microbial criteria, stress
      tolerance during processing, and storage of the product constitute the basis for
      the production of probiotics. Generally, the bacteria belonging to the genera
      Lactobacillus and Bifidobacterium have been used as probiotics. Based on their
      positive qualities, probiotic bacteria are widely used in the production of food.
      Interest in the incorporation of the probiotic bacteria into other products apart
      from dairy products has been increasing and represents a great challenge. The
      recognition of dose delivery systems for probiotic bacteria has also resulted in
      research efforts aimed at developing probiotic food outside the dairy sector.
      Producing probiotic juices has been considered more in the recent years, due to
      an increased concern in personal health of consumers. This review focuses on
      probiotics, prebiotics, and the microencapsulation of living cells.

PMID- 25848936
TI  - Formaldehyde N,N-dialkylhydrazones as neutral formyl anion equivalents in iridium
      catalyzed asymmetric allylic substitution.
AB  - The use of formaldehyde N,N-dialkylhydrazones as neutral C1-nucleophiles in the
      iridium-catalyzed substitution of allylic carbonates is described for two
      processes. Kinetic resolution or, alternatively, stereospecific substitution
      affords configurationally stable alpha,alpha-disubstituted aldehyde hydrazones in
      high enantiomeric excess and yield. This umpolung approach allows for the
      construction of optically active allylic nitriles and dithiolanes as well as
      branched alpha-aryl aldehydes. A catalyst-controlled reaction with Enders' chiral
      hydrazone derivatives followed by diastereoselective nucleophilic addition to the
      hydrazone products constitutes a two-step stereodivergent synthesis of chiral
      amines. 

PMID- 25848937
TI  - Team-Sport Athletes' Improvement of Performance on the Yo-Yo Intermittent
      Recovery Test Level 2, but Not of Time-Trial Performance, With Intermittent
      Hypoxic Training.
AB  - PURPOSE: To determine the time course for physical-capacity adaptations to
      intermittent hypoxic training (IHT) in team-sport athletes and the time course
      for benefits remaining after IHT. METHODS: A pre-post parallel-groups design was
      employed, with 21 Australian footballers assigned to IHT (n = 10) or control
      (CON; n = 11) matched for training load. IHT performed eleven 40-min bike
      sessions at 2500-m altitude over 4 wk. Yo-Yo Intermittent Recovery Test level 2
      (Yo-Yo IR2) was performed before; after 3, 6, and 11 IHT sessions; and 30 and 44
      d after IHT. Repeated time trials (2- and 1-km TTs, with 5 min rest) were
      performed before, after, and 3 wk after IHT. Hemoglobin mass (Hb(mass)) was
      measured in IHT before and after 3, 6, 9, and 11 sessions. RESULTS: Baseline Yo
      Yo IR2 was similar between groups. After 6 sessions, the change in Yo-Yo IR2 in
      IHT was very likely higher than CON (27% greater change, effect size 0.77, 90%
      confidence limits 0.20;1.33) and likely higher 1 d after IHT (23%, 0.68,
      0.05;1.30). The IHT group's change remained likely higher than CON 30 d after IHT
      (24%, 0.72, 0.12;1.33) but was not meaningfully different 44 d after (12%, 0.36, 
      0.24;0.97). The change in 2-km TT performance between groups was not different
      throughout. For 1-km TT, CON improved more after IHT, but IHT maintained
      performance better after 3 wk. Hb(mass) was higher after IHT (2.7%, 0.40, 
      0.40;1.19). CONCLUSION: Short-duration IHT increased Yo-Yo IR2 compared with
      training-load-matched controls in 2 wk. An additional 2 wk of IHT provided no
      further benefit. These changes remained until at least 30 d posttraining. IHT
      also protected improvement in 1-km TT.

PMID- 25848938
TI  - Socioeconomic indicators of health inequalities and female mortality: a nested
      cohort study within the United Kingdom Collaborative Trial of Ovarian Cancer
      Screening (UKCTOCS).
AB  - BACKGROUND: Evidence is mounting that area-level socioeconomic indicators are
      important tools for predicting health outcomes. However, few studies have
      examined these alongside individual-level education. This nested cohort study
      within the control arm of the United Kingdom Collaborative Trial of Ovarian
      Cancer Screening (UKCTOCS) assesses the association of mutually adjusted
      individual (education) and area-level (Index of Multiple Deprivation-IMD 2007)
      socioeconomic status indicators and all-cause female mortality. METHODS:
      Participants resident in England who had completed both baseline (Wave 1) and
      follow up (Wave 2) questionnaires were included. Follow-up was through the Health
      and Social Care Information Centre with deaths censored on 31st December 2012.
      IMD, education and a range of covariates were explored. Cox regression models
      adjusted for all covariates were used. Sensitivity analysis using imputation was
      performed (1) including those with missing data and (2) on the entire cohort who
      had completed the baseline questionnaire. RESULTS: Of the 54,539 women resident
      in England who completed both Wave 1 and Wave 2 questionnaires, 4,510 had missing
      data. The remaining 50,029 women were included in the primary analysis. Area
      level IMD was positively associated with all-cause mortality for the most
      deprived group compared to the least deprived (HR=1.42, CI=1.14-1.78) after
      adjusting for all potential confounders. Sensitivity analyses showed similar
      results with stronger associations in the entire cohort (HR=1.90, CI=1.68-2.16).
      The less educated an individual, the higher the mortality risk (test for trend
      p=<0.001). However, the crude effect on mortality of having no formal education
      compared to college/university education disappeared when adjusted for IMD rank
      (HR=1.08, CI=0.93-1.26). CONCLUSION: Women living in more deprived areas continue
      to have higher mortality even in this less deprived cohort and after adjustment
      for a range of potential confounders. TRIAL REGISTRATION: This study is
      registered as an International Standard Randomised Controlled Trial, number
      ISRCTN22488978.

PMID- 25848939
TI  - Variation at FCGR2A and functionally related genes is associated with the
      response to anti-TNF therapy in rheumatoid arthritis.
AB  - OBJECTIVE: Anti-TNF therapies have been highly efficacious in the management of
      rheumatoid arthritis (RA), but 25-30% of patients do not show a significant
      clinical response. There is increasing evidence that genetic variation at the Fc
      receptor FCGR2A is associated with the response to anti-TNF therapy. We aimed to
      validate this genetic association in a patient cohort from the Spanish
      population, and also to identify new genes functionally related to FCGR2A that
      are also associated with anti-TNF response. METHODS: A total of 348 RA patients
      treated with an anti-TNF therapy were included and genotyped for FCGR2A
      polymorphism rs1081274. Response to therapy was determined at 12 weeks, and was
      tested for association globally and independently for each anti-TNF drug
      (infliximab, etanercept and adalimumab). Using gene expression profiles from
      macrophages obtained from synovial fluid of RA patients, we searched for genes
      highly correlated with FCGR2A expression. Tag SNPs were selected from each
      candidate gene and tested for association with the response to therapy. RESULTS:
      We found a significant association between FCGR2A and the response to adalimumab
      (P=0.022). Analyzing the subset of anti-CCP positive RA patients (78%), we also
      found a significant association between FCGR2A and the response to infliximab
      (P=0.035). DHX32 and RGS12 were the most consistently correlated genes with
      FCGR2A expression in RA synovial fluid macrophages (P<0.001). We found a
      significant association between the genetic variation at DHX32 (rs12356233,
      corrected P=0.019) and a nominally significant association between RGS12 and the
      response to adalimumab (rs4690093, uncorrected P=0.040). In the anti-CCP positive
      group of patients, we also found a nominally significant association between
      RGS12 and the response to infliximab (rs2857859, uncorrected P=0.042).
      CONCLUSIONS: In the present study we have validated the FCGR2A association in an
      independent population, and we have identified new genes associated with the
      response to anti-TNF therapy in RA.

PMID- 25848940
TI  - EDB Fibronectin Specific Peptide for Prostate Cancer Targeting.
AB  - Extradomain-B fibronectin (EDB-FN), one of the oncofetal fibronectin (onfFN)
      isoforms, is a high-molecular-weight glycoprotein that mediates cell adhesion and
      migration. The expression of EDB-FN is associated with a number of cancer-related
      biological processes such as tumorigenesis, angiogenesis, and epithelial-to
      mesenchymal transition (EMT). Here, we report the development of a small peptide
      specific to EDB-FN for targeting prostate cancer. A cyclic nonapeptide, CTVRTSADC
      (ZD2), was identified using peptide phage display. A ZD2-Cy5 conjugate was
      synthesized to accomplish molecular imaging of prostate cancer in vitro and in
      vivo. ZD2-Cy5 demonstrated effective binding to up-regulated EDB-FN secreted by
      TGF-beta-induced PC3 cancer cells following EMT. Following intravenous
      injections, the targeted fluorescent probe specifically bound to and delineated
      PC3-GFP prostate tumors in nude mice bearing the tumor xenografts. ZD2-Cy5 also
      showed stronger binding to human prostate tumor specimens with a higher Gleason
      score (GS9) compared to those with a lower score (GS 7), with no binding in
      benign prostatic hyperplasia (BPH). Thus, the ZD2 peptide is a promising strategy
      for molecular imaging and targeted therapy of prostate cancer. 

PMID- 25848941
TI  - Lobular breast cancer: incidence and genetic and non-genetic risk factors.
AB  - While most invasive breast cancers consist of carcinomas of the ductal type,
      about 10% are invasive lobular carcinomas. Invasive lobular and ductal carcinomas
      differ with respect to risk factors. Invasive lobular carcinoma is more strongly
      associated with exposure to female hormones, and therefore its incidence is more
      subject to variation. This is illustrated by US figures during the 1987 to 2004
      period: after 12 years of increases, breast cancer incidence declined steadily
      from 1999 to 2004, reflecting among other causes the decreasing use of menopausal
      hormone therapy, and these variations were stronger for invasive lobular than for
      invasive ductal carcinoma. Similarly, invasive lobular carcinoma is more strongly
      associated with early menarche, late menopause and late age at first birth. As
      for genetic risk factors, four high-penetrance genes are tested in clinical
      practice when genetic susceptibility to breast cancer is suspected, BRCA1, BRCA2,
      TP53 and CDH1. Germline mutations in BRCA1 and TP53 are predominantly associated
      with invasive ductal carcinoma, while BRCA2 mutations are associated with both
      ductal and lobular cancers. CDH1, the gene coding for the E-cadherin adhesion
      protein, is of special interest as mutations are associated with invasive lobular
      carcinoma, but never with ductal carcinoma. It was initially known as the main
      susceptibility gene for gastric cancer of the diffuse type, but the excess of
      breast cancers of the lobular type in CDH1 families led researchers to identify
      it also as a susceptibility gene for invasive lobular carcinoma. The risk of
      invasive lobular carcinoma is high in female mutation carriers, as about 50% are
      expected to develop the disease. Carriers must therefore undergo intensive breast
      cancer screening, with, for example, yearly magnetic resonance imaging and
      mammogram starting at age 30 years. 

PMID- 25848942
TI  - Clinical outcomes in low risk coronary artery disease patients treated with
      different limus-based drug-eluting stents--a nationwide retrospective cohort
      study using insurance claims database.
AB  - The clinical outcomes of different limus-based drug-eluting stents (DES) in a
      real-world setting have not been well defined. The aim of this study was to
      investigate the clinical outcomes of three different limus-based DES, namely
      sirolimus-eluting stent (SES), Endeavor zotarolimus-eluting stent (E-ZES) and
      everolimus-eluting stent (EES), using a national insurance claims database. We
      identified all patients who received implantation of single SES, E-ZES or EES
      between January 1, 2007 and December 31, 2009 from the National Health Insurance
      claims database, Taiwan. Follow-up was through December 31, 2011 for all selected
      clinical outcomes. The primary end-point was all-cause mortality. Secondary end
      points included acute coronary events, heart failure needing hospitalization, and
      cerebrovascular disease. Cox regression model adjusting for baseline
      characteristics was used to compare the relative risks of different outcomes
      among the three different limus-based DES. Totally, 6584 patients were evaluated
      (n=2142 for SES, n=3445 for E-ZES, and n=997 for EES). After adjusting for
      baseline characteristics, we found no statistically significant difference in the
      risk of all-cause mortality in three DES groups (adjusted hazard ratio [HR]:
      1.14, 95% confidence interval [CI]: 0.94-1.38, p=0.20 in E-ZES group compared
      with SES group; adjusted HR: 0.77, 95% CI: 0.54-1.10, p=0.15 in EES group
      compared with SES group). Similarly, we found no difference in the three stent
      groups in risks of acute coronary events, heart failure needing hospitalization,
      and cerebrovascular disease. In conclusion, we observed no difference in all
      cause mortality, acute coronary events, heart failure needing hospitalization,
      and cerebrovascular disease in patients treated with SES, E-ZES, and EES in a
      real-world population-based setting in Taiwan. 

PMID- 25848943
TI  - Protein folding as a complex reaction: a two-component potential for the driving
      force of folding and its variation with folding scenario.
AB  - The Helmholtz decomposition of the vector field of probability fluxes in a two
      dimensional space of collective variables makes it possible to introduce a
      potential for the driving force of protein folding [Chekmarev, J. Chem. Phys. 139
      (2013) 145103]. The potential has two components: one component (Phi) is
      responsible for the source and sink of the folding flow, which represent,
      respectively, the unfolded and native state of the protein, and the other (Psi)
      accounts for the flow vorticity inherently generated at the periphery of the flow
      field and provides the canalization of the flow between the source and sink. Both
      components obey Poisson's equations with the corresponding source/sink terms. In
      the present paper, we consider how the shape of the potential changes depending
      on the scenario of protein folding. To mimic protein folding dynamics projected
      onto a two-dimensional space of collective variables, the two-dimensional Muller
      and Brown potential is employed. Three characteristic scenarios are considered: a
      single pathway from the unfolded to the native state without intermediates, two
      parallel pathways without intermediates, and a single pathway with an off-pathway
      intermediate. To determine the probability fluxes, the hydrodynamic description
      of the folding reaction is used, in which the first-passage folding is viewed as
      a steady flow of the representative points of the protein from the unfolded to
      the native state. We show that despite the possible complexity of the folding
      process, the Phi-component is simple and universal in shape. The Psi-component is
      more complex and reveals characteristic features of the process of folding. The
      present approach is potentially applicable to other complex reactions, for which
      the transition from the reactant to the product can be described in a space of
      two (collective) variables. 

PMID- 25848945
TI  - Correction: chemopreventive efficacy of Andrographis paniculata on azoxymethane
      induced aberrant colon Crypt Foci in vivo.

PMID- 25848944
TI  - A new method for discovering disease-specific MiRNA-target regulatory networks.
AB  - Genes and their expression regulation are among the key factors in the
      comprehension of the genesis and development of complex diseases. In this
      context, microRNAs (miRNAs) are post-transcriptional regulators that play an
      important role in gene expression since they are frequently deregulated in
      pathologies like cardiovascular disease and cancer. In vitro validation of miRNA-
      targets regulation is often too expensive and time consuming to be carried out
      for every possible alternative. As a result, a tool able to provide some criteria
      to prioritize trials is becoming a pressing need. Moreover, before planning in
      vitro experiments, the scientist needs to evaluate the miRNA-target genes
      interaction network. In this paper we describe the miRable method whose purpose
      is to identify new potentially relevant genes and their interaction networks
      associate to a specific pathology. To achieve this goal miRable follows a system
      biology approach integrating together general-purpose medical knowledge
      (literature, Protein-Protein Interaction networks, prediction tools) and
      pathology specific data (gene expression data). A case study on Prostate Cancer
      has shown that miRable is able to: 1) find new potential miRNA-targets pairs, 2)
      highlight novel genes potentially involved in a disease but never or little
      studied before, 3) reconstruct all possible regulatory subnetworks starting from
      the literature to expand the knowledge on the regulation of miRNA regulatory
      mechanisms.

PMID- 25848946
TI  - Synthesis and characterization of a series of [M2(beta-SiW8O31)2](n-) clusters
      and mechanistic insight into the reorganization of {beta-SiW8O31} into {alpha
      SiW9O34}.
AB  - Lacunary polyoxometalates of low nuclearity are difficult to synthesize in
      isolation. We report the facile synthesis of six {M2(B-beta-SiW8O31)2} clusters
      (M = Co/Mn/Ni/Zn/Cu(2+), Fe(3+)) that can be employed as building blocks for the
      formation of larger architectures. We show for the first time that such {B-beta
      SiW8O31} lacunae are capable of reorganizing into larger Keggin lacunary species
      even in the absence of an external source of tungstate. We hypothesize, based on
      electrospray ionization mass spectrometry evidence obtained, not only that such a
      transformation is only possible via an initial decomposition of the {SiW8}
      precursor into a {SiW6}-based intermediate but also that it is this {SiW6}
      species that acts as the template for the growth of the larger fragments. 

PMID- 25848947
TI  - Myofascial trigger points in patients with whiplash-associated disorders and
      mechanical neck pain.

PMID- 25848948
TI  - High-dose intravenous vitamin C combined with cytotoxic chemotherapy in patients
      with advanced cancer: a phase I-II clinical trial.
AB  - BACKGROUND: Biological and some clinical evidence suggest that high-dose
      intravenous vitamin C (IVC) could increase the effectiveness of cancer
      chemotherapy. IVC is widely used by integrative and complementary cancer
      therapists, but rigorous data are lacking as to its safety and which cancers and
      chemotherapy regimens would be the most promising to investigate in detail.
      METHODS AND FINDINGS: We carried out a phase I-II safety, tolerability,
      pharmacokinetic and efficacy trial of IVC combined with chemotherapy in patients
      whose treating oncologist judged that standard-of-care or off-label chemotherapy
      offered less than a 33% likelihood of a meaningful response. We documented
      adverse events and toxicity associated with IVC infusions, determined pre- and
      post-chemotherapy vitamin C and oxalic acid pharmacokinetic profiles, and
      monitored objective clinical responses, mood and quality of life. Fourteen
      patients were enrolled. IVC was safe and generally well tolerated, although some
      patients experienced transient adverse events during or after IVC infusions. The
      pre- and post-chemotherapy pharmacokinetic profiles suggested that tissue uptake
      of vitamin C increases after chemotherapy, with no increase in urinary oxalic
      acid excretion. Three patients with different types of cancer experienced
      unexpected transient stable disease, increased energy and functional improvement.
      CONCLUSIONS: Despite IVC's biological and clinical plausibility, career cancer
      investigators currently ignore it while integrative cancer therapists use it
      widely but without reporting the kind of clinical data that is normally gathered
      in cancer drug development. The present study neither proves nor disproves IVC's
      value in cancer therapy, but it provides practical information, and indicates a
      feasible way to evaluate this plausible but unproven therapy in an academic
      environment that is currently uninterested in it. If carried out in sufficient
      numbers, simple studies like this one could identify specific clusters of cancer
      type, chemotherapy regimen and IVC in which exceptional responses occur
      frequently enough to justify appropriately focused clinical trials. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT01050621.

PMID- 25848949
TI  - Timing of ripening initiation in grape berries and its relationship to seed
      content and pericarp auxin levels.
AB  - BACKGROUND: Individual berries in a grape (Vitis vinifera L.) cluster enter the
      ripening phase at different times leading to an asynchronous cluster in terms of
      ripening. The factors causing this variable ripening initiation among berries are
      not known. Because the influence via hormonal communication of the seed on fruit
      set and growth is well known across fruit species, differences in berry seed
      content and resultant quantitative or qualitative differences in the hormone
      signals to the pericarp likely influence the relative timing of ripening
      initiation among berries of the cluster. RESULTS: At the time of the initiation
      of cluster ripening (veraison), underripe green berries have higher seed content
      compared to the riper berries and there is a negative correlation between the
      seed weight-to-berry weight ratio (SB) and the sugar level in berries of a
      cluster. Auxin levels in seeds relative to the pericarp tissues are two to 12
      times higher at pre-ripening stages. The pericarp of berries with high-SB had
      higher auxin and lower abscisic acid (ABA) levels compared to those with low-SB
      from two weeks before veraison. In the preveraison cluster, the expression of
      auxin-response factor genes was significantly higher in the pericarp of high-SB
      berries and remained higher until veraison compared to low-SB berries. The
      expression level of auxin-biosynthetic genes in the pericarp was the same between
      both berry groups based upon similar expression activity of YUC genes that are
      rate-limiting factors in auxin biosynthesis. On the other hand, in low-SB
      berries, the expression of ABA-biosynthetic and ABA-inducible NCED and MYB genes
      was higher even two weeks before veraison. CONCLUSIONS: Differences in the
      relative seed content among berries plays a major role in the timing of ripening
      initiation. Towards the end of berry maturation phase, low and high levels of
      auxin are observed in the pericarp of low- and high-SB berries, respectively.
      This results in higher auxin-signaling activity that lasts longer in the pericarp
      of high-SB berries. In contrast, in low-SB berries, concomitant with an earlier
      decrease of auxin level, the features of ripening initiation, such as increases
      in ABA and sugar accumulation begin earlier.

PMID- 25848950
TI  - Perpendicular Magnetic Anisotropy and Spin Glass-like Behavior in Molecular Beam
      Epitaxy Grown Chromium Telluride Thin Films.
AB  - Reflection high-energy electron diffraction (RHEED), scanning tunneling
      microscopy (STM), vibrating sample magnetometry, and other physical property
      measurements are used to investigate the structure, morphology, magnetic, and
      magnetotransport properties of (001)-oriented Cr2Te3 thin films grown on
      Al2O3(0001) and Si(111)-(7*7) surfaces by molecular beam epitaxy. Streaky RHEED
      patterns indicate flat smooth film growth on both substrates. STM studies show
      the hexagonal arrangements of surface atoms. Determination of the lattice
      parameter from the atomically resolved STM image is consistent with the bulk
      crystal structures. Magnetic measurements show the film is ferromagnetic, having
      a Curie temperature of about 180 K, and a spin glass-like behavior was observed
      below 35 K. Magnetotransport measurements show the metallic nature of the film
      with a perpendicular magnetic anisotropy along the c-axis. 

PMID- 25848951
TI  - The default mode network and the working memory network are not anti-correlated
      during all phases of a working memory task.
AB  - INTRODUCTION: The default mode network and the working memory network are known
      to be anti-correlated during sustained cognitive processing, in a load-dependent
      manner. We hypothesized that functional connectivity among nodes of the two
      networks could be dynamically modulated by task phases across time. METHODS: To
      address the dynamic links between default mode network and the working memory
      network, we used a delayed visuo-spatial working memory paradigm, which allowed
      us to separate three different phases of working memory (encoding, maintenance,
      and retrieval), and analyzed the functional connectivity during each phase within
      and between the default mode network and the working memory network networks.
      RESULTS: We found that the two networks are anti-correlated only during the
      maintenance phase of working memory, i.e. when attention is focused on a
      memorized stimulus in the absence of external input. Conversely, during the
      encoding and retrieval phases, when the external stimulation is present, the
      default mode network is positively coupled with the working memory network,
      suggesting the existence of a dynamically switching of functional connectivity
      between "task-positive" and "task-negative" brain networks. CONCLUSIONS: Our
      results demonstrate that the well-established dichotomy of the human brain (anti
      correlated networks during rest and balanced activation-deactivation during
      cognition) has a more nuanced organization than previously thought and engages in
      different patterns of correlation and anti-correlation during specific sub-phases
      of a cognitive task. This nuanced organization reinforces the hypothesis of a
      direct involvement of the default mode network in cognitive functions, as
      represented by a dynamic rather than static interaction with specific task
      positive networks, such as the working memory network.

PMID- 25848952
TI  - Transcriptome analysis of Wnt3a-treated triple-negative breast cancer cells.
AB  - The canonical Wnt/beta-catenin pathway is activated in triple-negative breast
      cancer (TNBC). The activation of this pathway leads to the expression of specific
      target genes depending on the cell/tissue context. Here, we analyzed the
      transcriptome of two different TNBC cell lines to define a comprehensive list of
      Wnt target genes. The treatment of cells with Wnt3a for 6h up-regulated the
      expression (fold change > 1.3) of 59 genes in MDA-MB-468 cells and 241 genes in
      HCC38 cells. Thirty genes were common to both cell lines. Beta-catenin may also
      be a transcriptional repressor and we found that 18 and 166 genes were down
      regulated in response to Wnt3a treatment for 6h in MDA-MB-468 and HCC38 cells,
      respectively, of which six were common to both cell lines. Only half of the
      activated and the repressed transcripts have been previously described as Wnt
      target genes. Therefore, our study reveals 137 novel genes that may be positively
      regulated by Wnt3a and 104 novel genes that may be negatively regulated by Wnt3a.
      These genes are involved in the Wnt pathway itself, and also in TGFbeta, p53 and
      Hedgehog pathways. Thorough characterization of these novel potential Wnt target
      genes may reveal new regulators of the canonical Wnt pathway. The comparison of
      our list of Wnt target genes with those published in other cellular contexts
      confirms the notion that Wnt target genes are tissue-, cell line- and treatment
      specific. Genes up-regulated in Wnt3a-stimulated cell lines were more strongly
      expressed in TNBC than in luminal A breast cancer samples. These genes were also
      overexpressed, but to a much lesser extent, in HER2+ and luminal B tumors. We
      identified 72 Wnt target genes higher expressed in TNBCs (17 with a fold change
      >1.3) which may reflect the chronic activation of the canonical Wnt pathway that
      occurs in TNBC tumors. 

PMID- 25848953
TI  - Structure-Function Assessment of Mannosylated Poly(beta-amino esters) upon
      Targeted Antigen Presenting Cell Gene Delivery.
AB  - Antigen presenting cell (APC) gene delivery is a promising avenue for modulating
      immunological outcomes toward a desired state. Recently, our group developed a
      delivery methodology to elicit targeted and elevated levels of APC-mediated gene
      delivery. During these initial studies, we observed APC-specific structure
      function relationships with the vectors used during gene delivery that differ
      from current non-APC cell lines, thus, emphasizing a need to re-evaluate vector
      associated parameters in the context of APC gene transfer. Thus, we describe the
      synthesis and characterization of a second-generation mannosylated poly(beta
      amino ester) library stratified by molecular weight. To better understand the APC
      specific structure-function relationships governing polymeric gene delivery, the
      library was systematically characterized by (1) polymer molecular weight, (2)
      relative mannose content, (3) polyplex biophysical properties, and (4) gene
      delivery efficacy. In this library, polymers with the lowest molecular weight and
      highest relative mannose content possessed gene delivery transfection
      efficiencies as good as or better than commercial controls. Among this group, the
      most effective polymers formed the smallest polymer-plasmid DNA complexes (~300
      nm) with moderate charge densities (<10 mV). This convergence in polymer
      structure and polyplex biophysical properties suggests a unique mode of action
      and provides a framework within which future APC-targeting polymers can be
      designed. 

PMID- 25848955
TI  - Giants in chest medicine: Jay A. Nadel, MD.

PMID- 25848954
TI  - The E3 ubiquitin ligase HOS1 is involved in ethylene regulation of leaf expansion
      in Arabidopsis.
AB  - Ethylene regulates a variety of physiological processes, such as flowering,
      senescence, abscission, and fruit ripening. In particular, leaf expansion is also
      controlled by ethylene in Arabidopsis. Exogenous treatment with ethylene inhibits
      leaf expansion, and consistently, ethylene insensitive mutants show increased
      leaf area. Here, we report that the RING finger-containing E3 ubiquitin ligase
      HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENES 1 (HOS1) regulates leaf expansion
      in an ethylene signaling pathway. The HOS1-deficient mutant showed reduced leaf
      area and was insensitive to ethylene perception inhibitor, silver thiosulfate
      (STS). Accordingly, genes encoding ethylene signaling components were
      significantly up-regulated in hos1-3. This study demonstrates that the HOS1
      protein is involved in ethylene signal transduction for the proper regulation of
      leaf expansion possibly under environmentally stressful conditions. 

PMID- 25848956
TI  - A 39-year-old woman with palpitations and dyspnea.

PMID- 25848957
TI  - Methylene blue protects astrocytes against glucose oxygen deprivation by
      improving cellular respiration.
AB  - Astrocytes outnumber neurons and serve many metabolic and trophic functions in
      the mammalian brain. Preserving astrocytes is critical for normal brain function
      as well as for protecting the brain against various insults. Our previous studies
      have indicated that methylene blue (MB) functions as an alternative electron
      carrier and enhances brain metabolism. In addition, MB has been shown to be
      protective against neurodegeneration and brain injury. In the current study, we
      investigated the protective role of MB in astrocytes. Cell viability assays
      showed that MB treatment significantly protected primary astrocytes from oxygen
      glucose deprivation (OGD) & reoxygenation induced cell death. We also studied the
      effect of MB on cellular oxygen and glucose metabolism in primary astrocytes
      following OGD-reoxygenation injury. MB treatment significantly increased cellular
      oxygen consumption, glucose uptake and ATP production in primary astrocytes. In
      conclusion our study demonstrated that MB protects astrocytes against OGD
      reoxygenation injury by improving astrocyte cellular respiration. 

PMID- 25848959
TI  - (77)Se nuclear spin-lattice relaxation in binary Ge-Se glasses: insights into
      floppy versus rigid behavior of structural units.
AB  - The mechanism of (77)Se nuclear spin-lattice relaxation is investigated in binary
      Ge-Se glasses. The (77)Se nuclides in Se-Se-Se chain sites relax faster via
      dipolar coupling fluctuation compared to those in Ge-Se-Ge sites shared by GeSe4
      tetrahedra that relax slower via the fluctuation of the chemical shift
      anisotropy. The relaxation rate for the Se-Se-Se sites decreases markedly with
      increasing magnetic field, whereas that for the Ge-Se-Ge sites displays no
      appreciable dependence on the magnetic field such that the extent of differential
      relaxation between the two Se environments becomes small at high fields on the
      order of 19.6 T. The corresponding dynamical correlation time is three orders of
      magnitude shorter (~10(-9) s) for the Se-Se-Se sites, compared to that for the Ge
      Se-Ge sites (~10(-6) s). The large decoupling in the time scale between these Se
      environments provides direct experimental support to the commonly made assumption
      that the selenium chains are mechanically floppy, and the interconnected GeSe4
      tetrahedra form the rigid elements in the selenide glass structure. 

PMID- 25848958
TI  - Eighteenth-century genomes show that mixed infections were common at time of peak
      tuberculosis in Europe.
AB  - Tuberculosis (TB) was once a major killer in Europe, but it is unclear how the
      strains and patterns of infection at 'peak TB' relate to what we see today. Here
      we describe 14 genome sequences of M. tuberculosis, representing 12 distinct
      genotypes, obtained from human remains from eighteenth-century Hungary using
      metagenomics. All our historic genotypes belong to M. tuberculosis Lineage 4.
      Bayesian phylogenetic dating, based on samples with well-documented dates, places
      the most recent common ancestor of this lineage in the late Roman period. We find
      that most bodies yielded more than one M. tuberculosis genotype and we document
      an intimate epidemiological link between infections in two long-dead individuals.
      Our results suggest that metagenomic approaches usefully inform detection and
      characterization of historical and contemporary infections. 

PMID- 25848960
TI  - Pd clusters supported on amorphous, low-porosity carbon spheres for hydrogen
      production from formic acid.
AB  - Amorphous, low-porosity carbon spheres on the order of a few micrometers in size
      were prepared by carbonization of squalane (C30H62) in supercritical CO2 at 823
      K. The spheres were characterized and used as catalysts' supports for Pd. Near
      edge X-ray absorption fine structure studies of the spheres revealed sp(2) and
      sp(3) hybridized carbon. To activate carbons for interaction with a metal
      precursor, often oxidative treatment of a support is needed. We showed that
      boiling of the obtained spheres in 28 wt % HNO3 did not affect the shape and bulk
      structure of the spheres, but led to creation of a considerable amount of surface
      oxygen-containing functional groups and increase of the content of sp(2)
      hybridized carbon on the surface. This carbon was seen by scanning transmission
      electron microscopy in the form of waving graphene flakes. The H/C atomic ratio
      in the spheres was relatively high (0.4) and did not change with the HNO3
      treatment. Palladium was deposited by impregnation with Pd acetate followed by
      reduction in H2. This gave uniform Pd clusters with a size of 2-4 nm. The Pd
      supported on the original C spheres showed 2-3 times higher catalytic activity in
      vapor phase formic acid decomposition and higher selectivity for H2 formation (98
      99%) than those for the catalyst based on the HNO3 treated spheres. Using of such
      low-porosity spheres as a catalyst support should prevent mass transfer
      limitations for fast catalytic reactions. 

PMID- 25848961
TI  - Rough-fuzzy clustering and unsupervised feature selection for wavelet based MR
      image segmentation.
AB  - Image segmentation is an indispensable process in the visualization of human
      tissues, particularly during clinical analysis of brain magnetic resonance (MR)
      images. For many human experts, manual segmentation is a difficult and time
      consuming task, which makes an automated brain MR image segmentation method
      desirable. In this regard, this paper presents a new segmentation method for
      brain MR images, integrating judiciously the merits of rough-fuzzy computing and
      multiresolution image analysis technique. The proposed method assumes that the
      major brain tissues, namely, gray matter, white matter, and cerebrospinal fluid
      from the MR images are considered to have different textural properties. The
      dyadic wavelet analysis is used to extract the scale-space feature vector for
      each pixel, while the rough-fuzzy clustering is used to address the uncertainty
      problem of brain MR image segmentation. An unsupervised feature selection method
      is introduced, based on maximum relevance-maximum significance criterion, to
      select relevant and significant textural features for segmentation problem, while
      the mathematical morphology based skull stripping preprocessing step is proposed
      to remove the non-cerebral tissues like skull. The performance of the proposed
      method, along with a comparison with related approaches, is demonstrated on a set
      of synthetic and real brain MR images using standard validity indices. 

PMID- 25848962
TI  - Correction: Genome-wide association analysis with gray matter volume as a
      quantitative phenotype in first-episode treatment-naive patients with
      schizophrenia.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0075083.]. 

PMID- 25848963
TI  - Preventive Effect of Tephrosia purpurea on Selenite-Induced Experimental
      Cataract.
AB  - PURPOSE: Recent investigations have shown that phytochemical antioxidants can
      scavenge free radicals and prevent various diseases like cataract. The objective
      of the present study was to assess the efficacy of the Tephrosia purpurea in
      preventing these changes in the lens of selenite-induced cataract models.
      MATERIALS AND METHODS: Cataract was induced by a single injection of sodium
      selenite (4 mg/kg, s.c.) to 9-day-old Sprague-Dawley rat pups. The treatment with
      different extracts of T. purpurea was started on 10th day and continued for 30
      days in pups pretreated with sodium selenite. The animals were treated orally
      with either quercetin (1 mg/kg), flavonoid rich fraction (40 mg/kg) or alcohol
      extract (300 mg/kg) of T. purpurea. Cataract was visualized after 30 days.
      Encapsulated lenses were analyzed for reduced glutathione and malondialdehyde.
      Lenses were also analyzed for total protein, insoluble protein, total nitrite,
      calcium levels, protein sulfhydryl content as well as for the activities of
      superoxide dismutase and Ca(2+)-ATPase. RESULTS: Morphological examination of the
      rat lenses revealed normal transparent lens with minimal or partial nuclear
      opacity in control whereas dense opacity developed in rat lens treated with
      selenite. Both the extracts of T. purpurea produced reduction in nuclear opacity
      as well as improvement in the insoluble proteins, protein sulfhydryl, total
      nitrite, calcium levels and Ca(2+)-ATPase activity in lenses. The extracts
      decreased malondialdehyde levels but also prevented the loss of reduced
      glutathione levels. CONCLUSION: Our data suggests therapeutic potential of T.
      purpurea for the treatment of cataract.

PMID- 25848964
TI  - Subjective Reality: The Influence of Perceived and Objective Conversational
      Valence on Binge Drinking Determinants.
AB  - Previous studies have shown that interpersonal communication, and particularly
      perceived conversational valence (i.e., the perceived negativity or positivity of
      conversations) about health topics, influences health determinants. On the basis
      of 43 dyads (N = 86) discussing the topic of alcohol consumption, this study is
      the first to show that whereas perceived and objective conversational valence are
      positively related, only perceived conversational valence is a significant
      predictor of binge drinking attitudes and intentions. Thus, subjective reality
      matters more than objective reality. Furthermore, only the perceived valence of
      the participants' own contributions-and not of their conversation partners-
      influences binge drinking intentions, indicating that self-persuasion is more
      influential than persuasion by others. Thus, conversations in which discussants
      themselves express negative opinions about unhealthy behaviors can enhance public
      health.

PMID- 25848965
TI  - Effects of body mass index on risks for ischemic stroke, thromboembolism, and
      mortality in Chinese atrial fibrillation patients: a single-center experience.
AB  - BACKGROUND: Obesity is considered to be related to recurrence of atrial
      fibrillation (AF), left atrial thrombus formation, and atrial remodeling.
      However, whether obesity is an independent risk factor for stroke and other
      thromboembolic events is still controversial. OBJECTIVE: This study aimed to
      investigate the effects of body mass index (BMI) on the risks of stroke,
      thromboembolism, and mortality in AF patients. METHODS: Patients who were
      diagnosed with nonvalvular AF were included in this observational, retrospective
      study. The study population was stratified by BMI at baseline. The Cox
      proportional hazard model was adopted to calculate adjusted hazard ratios of risk
      factors for adverse clinical events (stroke, thromboembolism, and mortality).
      RESULTS: A total of 1286 AF patients (males, 78.30%; mean age, 74.50 years;
      94.48% paroxysmal AF) were followed up for a median of 2.1 years (IQR: 1.5-2.9
      years). Overall, 159 patients died. A total of 84 strokes and 35 thromboembolic
      events occurred. Multivariate analysis showed that overweight (25.0<=BMI<30.0
      kg/m2) and age >=75 years were independent risk factors for ischemic stroke (both
      P<0.01). Obesity (BMI >=30.0 kg/m2), age >=75 years, persistent/permanent AF, and
      prior thromboembolism were independent risk factors for thromboembolism (all
      P<0.05). Underweight (BMI <18.5 kg/m2), age >=75 years, prior ischemic
      stroke/transient ischemic attack, renal dysfunction, and heart failure were
      independent risk factors for all-cause deaths (all P<0.05). CONCLUSIONS:
      Overweight or obesity may be a risk factor of ischemic stroke and thromboembolism
      in AF patients. Excessive low weight is significantly associated with increased
      all-cause mortality.

PMID- 25848966
TI  - Structure-Based Prediction of G-Protein-Coupled Receptor Ligand Function: A beta
      Adrenoceptor Case Study.
AB  - The spectacular advances in G-protein-coupled receptor (GPCR) structure
      determination have opened up new possibilities for structure-based GPCR ligand
      discovery. The structure-based prediction of whether a ligand stimulates
      (full/partial agonist), blocks (antagonist), or reduces (inverse agonist) GPCR
      signaling activity is, however, still challenging. A total of 31 beta1 (beta1R)
      and beta2 (beta2R) adrenoceptor crystal structures, including antagonist, inverse
      agonist, and partial/full agonist-bound structures, allowed us to explore the
      possibilities and limitations of structure-based prediction of GPCR ligand
      function. We used all unique protein-ligand interaction fingerprints (IFPs)
      derived from all ligand-bound beta-adrenergic crystal structure monomers to post
      process the docking poses of known beta1R/beta2R partial/full agonists,
      antagonists/inverse agonists, and physicochemically similar decoys in each of the
      beta1R/beta2R structures. The systematic analysis of these 1920 unique IFP
      structure combinations offered new insights into the relative impact of protein
      conformation and IFP scoring on selective virtual screening (VS) for ligands with
      a specific functional effect. Our studies show that ligands with the same
      function can be efficiently classified on the basis of their protein-ligand
      interaction profile. Small differences between the receptor conformation (used
      for docking) and reference IFP (used for scoring of the docking poses) determine,
      however, the enrichment of specific ligand types in VS hit lists. Interestingly,
      the selective enrichment of partial/full agonists can be achieved by using
      agonist IFPs to post-process docking poses in agonist-bound as well as antagonist
      bound structures. We have identified optimal structure-IFP combinations for the
      identification and discrimination of antagonists/inverse agonist and partial/full
      agonists, and defined a predicted IFP for the small full agonist norepinephrine
      that gave the highest retrieval rate of agonists over antagonists for all
      structures (with an enrichment factor of 46 for agonists and 8 for antagonists on
      average at a 1% false-positive rate). This beta-adrenoceptor case study provides
      new insights into the opportunities for selective structure-based discovery of
      GPCR ligands with a desired function and emphasizes the importance of IFPs in
      scoring docking poses. 

PMID- 25848967
TI  - An Abeta42 uptake and degradation via Rg3 requires an activation of caveolin,
      clathrin and Abeta-degrading enzymes in microglia.
AB  - We demonstrated previously that ginsenoside Rg3 enhances the expression of
      macrophage scavenger receptor class A (SRA) and amyloid beta peptide 1-42
      (Abeta42) uptake in BV2 cells. In this study, we investigated the biochemical and
      mechanistic roles of Rg3 in human microglia and animal models to identify the
      determinants that participate in restoring memory and learning in brains
      disrupted by the Abeta42 peptide. SRA was expressed highly in Rg3-treated rats,
      and learning and memory functions were maintained at a normal level after the
      infusion of Abeta42. SRA-transfected HMO6 human microglial cells (HMO6.hSRA)
      overexpressed SRA and took up a remarkable amount of Abeta42. Rg3-treated HMO6
      cells showed highly enhanced SRA expression and dramatically promoted Abeta42
      uptake. Moreover, high levels of clathrin and caveolin1 supported the roles of
      Rg3 in endocytic biogenesis by activating p38 and extracellular signal-regulated
      protein kinase signaling. Notably, both neprilysin (NEP) and insulin-degrading
      enzyme (IDE) were significantly expressed by Rg3, suggesting independent and
      compensatory hydrolytic activity for the Abeta peptide. In conclusion, Rg3
      successfully triggered Abeta42 uptake via SRA and clathrin-/caveolae-mediated
      endocytic mechanisms and further contributed to accelerate the degradation of
      Abeta peptide via the increase of intracellular NEP and IDE, which may be a
      promising Alzheimer's disease therapy.

PMID- 25848968
TI  - Trans-Pacific RAD-Seq population genomics confirms introgressive hybridization in
      Eastern Pacific Pocillopora corals.
AB  - Discrepancies between morphology-based taxonomy and phylogenetic systematics are
      common in Scleractinian corals. In Pocillopora corals, nine recently identified
      genetic lineages disagree fundamentally with the 17 recognized Pocillopora
      species, including 5 major Indo-Pacific reef-builders. Pocillopora corals
      hybridize in the Tropical Eastern Pacific, so it is possible that some of the
      disagreement between the genetics and taxonomy may be due to introgressive
      hybridization. Here we used 6769 genome-wide SNPs from Restriction-site
      Associated DNA Sequencing (RAD-Seq) to conduct phylogenomic comparisons among
      three common, Indo-Pacific Pocillopora species - P. damicornis, P. eydouxi and P.
      elegans - within and between populations in the Tropical Eastern Pacific (TEP)
      and the Central Pacific. Genome-wide RAD-Seq comparisons of Central and TEP
      Pocillopora confirm that the morphospecies P. damicornis, P. eydouxi and P.
      elegans are not monophyletic, but instead fall into three distinct genetic
      groups. However, hybrid samples shared fixed alleles with their respective
      parental species and, even without strict monophyly, P. damicornis share a common
      set of 33 species-specific alleles across the Pacific. RAD-Seq data confirm the
      pattern of one-way introgressive hybridization among TEP Pocillopora, suggesting
      that introgression may play a role in generating shared, polyphyletic lineages
      among currently recognized Pocillopora species. Levels of population
      differentiation within genetic lineages indicate significantly higher levels of
      population differentiation in the Tropical Eastern Pacific than in the Central
      West Pacific. 

PMID- 25848969
TI  - Dissecting signal and noise in diatom chloroplast protein encoding genes with
      phylogenetic information profiling.
AB  - Previous analyses of single diatom chloroplast protein-encoded genes recovered
      results highly incongruent with both traditional phylogenies and phylogenies
      derived from the nuclear encoded small subunit (SSU) gene. Our analysis here of
      six individual chloroplast genes (atpB, psaA, psaB, psbA, psbC and rbcL) obtained
      similar anomalous results. However, phylogenetic noise in these genes did not
      appear to be correlated, and their concatenation appeared to effectively sum
      their collective signal. We empirically demonstrated the value of combining
      phylogenetic information profiling, partitioned Bremer support and entropy
      analysis in examining the utility of various partitions in phylogenetic analysis.
      Noise was low in the 1st and 2nd codon positions, but so was signal. Conversely,
      high noise levels in the 3rd codon position was accompanied by high signal.
      Perhaps counterintuitively, simple exclusion experiments demonstrated this was
      especially true at deeper nodes where the 3rd codon position contributed most to
      a result congruent with morphology and SSU (and the total evidence tree here).
      Correlated with our empirical findings, probability of correct signal (derived
      from information profiling) increased and the statistical significance of
      substitutional saturation decreased as data were aggregated. In this regard, the
      aggregated 3rd codon position performed as well or better than more slowly
      evolving sites. Simply put, direct methods of noise removal (elimination of fast
      evolving sites) disproportionately removed signal. Information profiling and
      partitioned Bremer support suggest that addition of chloroplast data will rapidly
      improve our understanding of the diatom phylogeny, but conversely also illustrate
      that some parts of the diatom tree are likely to remain recalcitrant to addition
      of molecular data. The methods based on information profiling have been
      criticized for their numerous assumptions and parameter estimates and the fact
      that they are based on quartets of taxa. Our empirical results support
      theoretical arguments that the simplifying assumptions made in these methods are
      robust to "real-life" situations. 

PMID- 25848970
TI  - A multi-gene dataset reveals a tropical New World origin and Early Miocene
      diversification of croakers (Perciformes: Sciaenidae).
AB  - Widely distributed groups of living animals, such as the predominantly marine
      fish family Sciaenidae, have always attracted the attention of biogeographers to
      document the origins and patterns of diversification in time and space. In this
      study, the historical biogeography of the global Sciaenidae is reconstructed
      within a molecular phylogenetic framework to investigate their origin and to test
      the hypotheses explaining the present-day biogeographic patterns. Our data matrix
      comprises six mitochondrial and nuclear genes in 93 globally sampled sciaenid
      species from 52 genera. Within the inferred phylogenetic tree of the Sciaenidae,
      we identify 15 main and well-supported lineages; some of which have not been
      recognized previously. Reconstruction of habitat preferences shows repeated
      habitat transitions between marine and euryhaline environments. This implies that
      sciaenids can easily adapt to some variations in salinity, possibly as the
      consequence of their nearshore habitats and migratory life history. Conversely,
      complete marine/euryhaline to freshwater transitions occurred only three times,
      in South America, North America and South Asia. Ancestral range reconstruction
      analysis concomitant with fossil evidence indicates that sciaenids first
      originated and diversified in the tropical America during the Oligocene to Early
      Miocene before undergoing two range expansions, to Eastern Atlantic and to the
      Indo-West Pacific where a maximum species richness is observed. The uncommon
      biogeographic pattern identified is discussed in relation to current knowledge on
      origin of gradients of marine biodiversity toward the center of origin hypothesis
      in the Indo-West Pacific. 

PMID- 25848971
TI  - A ratiometric biosensor for metallothionein based on a dual heterogeneous electro
      chemiluminescent response from a TiO2 mesocrystalline interface.
AB  - An ultrasensitive dual-signal electro-chemiluminescent intelligent biosensor
      constructed from superstructure TiO2 mesocrystals is proposed for the detection
      of metallothionein. 

PMID- 25848972
TI  - Multinormal in vitro distribution of Plasmodium falciparum susceptibility to
      piperaquine and pyronaridine.
AB  - BACKGROUND: In 2002, the World Health Organization recommended that artemisinin
      based combination therapy (ACT) be used to treat uncomplicated malaria.
      Dihydroartemisinin-piperaquine and artesunate-pyronaridine are two of these new
      combinations. The aim of the present work was to assess the distribution of the
      in vitro values of pyronaridine (PND) and piperaquine (PPQ) and to define a cut
      off for reduced susceptibility for the two anti-malarial drugs. METHODS: The
      distribution and range of the 50% inhibitory concentration values (IC50) of PND
      and PPQ were determined for 313 isolates obtained between 2008 and 2012 from
      patients hospitalized in France for imported malaria. The statistical Bayesian
      analysis was designed to answer the specific question of whether Plasmodium
      falciparum has different phenotypes of susceptibility to PND and PPQ. RESULTS:
      The PND IC50 values ranged from 0.6 to 84.6 nM, with a geometric mean of 21.1 +/-
      16.0 nM (standard deviation). These values were classified into three components.
      The PPQ IC50 values ranged from 9.8 to 217.3 nM, and the geometric mean was 58.0
      +/- 34.5 nM. All 313 PPQ values were classified into four components. Isolates
      with IC50 values greater than 60 nM or four-fold greater than 3D7 IC50 are
      considered isolates that have reduced susceptibility to PND and those with IC50
      values greater than 135 nM or 2.3-fold greater than 3D7 IC50 are considered
      isolates that have reduced susceptibility to PPQ. CONCLUSION: The existence of at
      least three phenotypes for PND and four phenotypes for PPQ was demonstrated.
      Based on the cut-off values, 18 isolates (5.8%) and 13 isolates (4.2%)
      demonstrated reduced susceptibility to PND and PPQ, respectively.

PMID- 25848973
TI  - Correlation of plasma catestatin level and the prognosis of patients with acute
      myocardial infarction.
AB  - Catestatin is a peptide which is a potent inhibitor of catecholamine secretion
      and played essential functions in the cardiovascular system. Previous research
      found that dramatic changes of catestatin were associated with hemodynamics in
      acute myocardial infarction (AMI) during the first week after the AMI symptoms
      onset, but whether catestatin is also involved in the pathophysiological
      progression after AMI and then a predictor for outcomes is not clear. The aim of
      this study is to determine the correlation of plasma catestatin levels at
      different time points and the prognosis of AMI. 100 participants recruited were
      all patients with AMI, all of who received successful primary percutaneous
      coronary intervention (PCI) within 12h from the AMI symptom onset in our center;
      the concentrations of plasma catestatin were evaluated from blood samples of
      those 100 participants. Subsequent 65 months' follow-up was performed after
      discharging to evaluate cardiac adverse events and the association between
      catestatin levels and prognosis of AMI was examined. We confirmed the dramatic
      change of catestatin concentrations in the first week of AMI, and the levels of
      catestatin on D3 were much higher in adverse events group than those in non
      adverse events group (p<0.0001), but the ratio of D7/D3 was significantly lower.
      In addition, the Kaplan-Meier analysis showed that the groups in which the levels
      on D3 were higher (p<0.0001) and the ratios of D7/D3 were lower (p<0.0001),
      patients trended to be more susceptive to adverse events after AMI. Furthermore,
      according to the analysis, we surmised catestatin level on D3 as an appropriate
      predictor for outcomes in patients with AMI with good specificity as well as
      sensitivity. All of the evidence confirmed that catestatin plays an important
      role in the progress of AMI, and may act as a promising target for prognostic
      prediction. 

PMID- 25848974
TI  - New acylated anthocyanins from purple yam and their antioxidant activity.
AB  - Purple yam (Dioscorea alata L.), which is widely distributed in tropical and
      subtropical regions, is characterized by its color and viscosity. Previous
      studies have shown that purple yams contain a variety of acylated anthocyanins
      that exhibit higher levels of antioxidant activity than the corresponding
      nonacylated compounds. In this study, the pigments found in purple yams from the
      Philippines (D. alata) were isolated and evaluated in terms of antioxidant
      activity. Four new acylated anthocyanins, alanins (1-4) were isolated from the
      MeOH extracts of purple yam, which were subsequently determined to be cyanidin
      (1, 2, and 4) and peonidin (3) type compounds, along with four known anthocyanins
      (5-8). The structures of 1-4 were determined by spectroscopic methods, including
      NMR and MS analyses. The antioxidant activities of anthocyanins 1-8 were
      investigated using oxygen radical absorbing capacity and ferric reducing
      antioxidant power assays.

PMID- 25848975
TI  - A combined molecular dynamic and quantum mechanic study of the solvent and guest
      molecule effect on the stability and length of heterocyclic peptide nanotubes.
AB  - Molecular dynamic simulations were performed to investigate the stability of
      heterocyclic peptide nanotubes composed of 1,4-disubstituted-1,2,3-triazol
      epsilon-amino acid. 45 ns MD simulations were conducted on the cyclic peptide
      nanotube (CPNT) and cyclic peptide dimer in methanol, chloroform, and water and
      revealed that these structures are more stable in nonpolar solvents. MM-PBSA and
      MM-GBSA calculations were employed to analyze the solvent effect on the stability
      and length of the CPNT. These calculations showed that CPNT in chloroform was
      more stable and longer as compared to other solvents. In addition, the effect of
      the guest molecule (ethanol) inside the dimer and CPNT was investigated. The
      obtained results confirmed that guest molecule(s) stabilized the dimer and CPNT
      in all solvents. Quantum chemistry calculations on the cyclic peptide dimer were
      performed at the M06-2X/6-31G(d) level in the gas phase and three solvents. The
      obtained results from the quantum chemistry study were in good agreement with the
      MD simulation results. DFT calculations showed that the guest molecule stabilized
      the dimer structure and electrostatically interacted with the cyclic peptide
      dimer. Finally, for investigation of the solvent effects on the hydrogen bonds of
      the cyclic peptide dimer, NBO and AIM analysis were performed. 

PMID- 25848976
TI  - Association of Common Genetic Polymorphisms with Melanoma Patient IL-12p40 Blood
      Levels, Risk, and Outcomes.
AB  - Recent investigation has identified association of IL-12p40 blood levels with
      melanoma recurrence and patient survival. No studies have investigated
      associations of single-nucleotide polymorphisms (SNPs) with melanoma patient IL
      12p40 blood levels or their potential contributions to melanoma susceptibility or
      patient outcome. In the current study, 818,237 SNPs were available for 1,804
      melanoma cases and 1,026 controls. IL-12p40 blood levels were assessed among 573
      cases (discovery), 249 cases (case validation), and 299 controls (control
      validation). SNPs were evaluated for association with log[IL-12p40] levels in the
      discovery data set and replicated in two validation data sets, and significant
      SNPs were assessed for association with melanoma susceptibility and patient
      outcomes. The most significant SNP associated with log[IL-12p40] was in the IL
      12B gene region (rs6897260, combined P=9.26 * 10(-38)); this single variant
      explained 13.1% of variability in log[IL-12p40]. The most significant SNP in EBF1
      was rs6895454 (combined P=2.24 * 10(-9)). A marker in IL12B was associated with
      melanoma susceptibility (rs3213119, multivariate P=0.0499; OR=1.50, 95% CI 1.00
      2.24), whereas a marker in EBF1 was associated with melanoma-specific survival in
      advanced-stage patients (rs10515789, multivariate P=0.02; HR=1.93, 95% CI 1.11
      3.35). Both EBF1 and IL12B strongly regulate IL-12p40 blood levels, and IL-12p40
      polymorphisms may contribute to melanoma susceptibility and influence patient
      outcome. 

PMID- 25848977
TI  - Aurora Kinase A Is Upregulated in Cutaneous T-Cell Lymphoma and Represents a
      Potential Therapeutic Target.
AB  - Cutaneous T-cell lymphomas (CTCLs) form a heterogeneous group of non-Hodgkin's
      lymphomas characterized by only poor prognosis in advanced stage. Despite
      significant progress made in the identification of novel genes and pathways
      involved in the pathogenesis of cutaneous lymphoma, the therapeutic value of
      these findings has still to be proven. Here, we demonstrate by gene expression
      arrays that Aurora kinase A is one of the highly overexpressed genes of the
      serine/threonine kinase in CTCL. The finding was confirmed by quantitative
      reverse transcriptase-PCR, western blotting, and immunohistochemistry in CTCL
      cell lines and primary patient samples. Moreover, treatment with a specific
      Aurora kinase A inhibitor blocks cell proliferation by inducing cell cycle arrest
      in G2 phase, as well as apoptosis in CTCL cell lines. These data provide a
      promising rationale for using Aurora kinase A inhibition as a therapeutic
      modality of CTCL. 

PMID- 25848978
TI  - Molecular and Morphological Characterization of Inflammatory Infiltrate in
      Rosacea Reveals Activation of Th1/Th17 Pathways.
AB  - Rosacea is a common chronic inflammatory skin disease of unknown etiology. Our
      knowledge about an involvement of the adaptive immune system is very limited. We
      performed detailed transcriptome analysis, quantitative real-time reverse
      transcriptase-PCR, and quantitative immunohistochemistry on facial biopsies of
      rosacea patients, classified according to their clinical subtype. As controls, we
      used samples from patients with facial lupus erythematosus and healthy controls.
      Our study shows significant activation of the immune system in all subtypes of
      rosacea, characterizing erythematotelangiectatic rosacea (ETR) already as a
      disease with significant influx of proinflammatory cells. The T-cell response is
      dominated by Th1/Th17-polarized immune cells, as demonstrated by significant
      upregulation of IFN-gamma or IL-17, for example. Chemokine expression patterns
      support a Th1/Th17 polarization profile of the T-cell response. Macrophages and
      mast cells are increased in all three subtypes of rosacea, whereas neutrophils
      reach a maximum in papulopustular rosacea. Our studies also provide evidence for
      the activation of plasma cells with significant antibody production already in
      ETR, followed by a crescendo pattern toward phymatous rosacea. In sum, Th1/Th17
      polarized inflammation and macrophage infiltration are an underestimated hallmark
      in all subtypes of rosacea. Therapies directly targeting the Th1/Th17 pathway are
      promising candidates in the future treatment of this skin disease. 

PMID- 25848979
TI  - Differential Changes in the Peptidergic and the Non-Peptidergic Skin Innervation
      in Rat Models for Inflammation, Dry Skin Itch, and Dermatitis.
AB  - Skin innervation is a dynamic process that may lead to changes in nerve fiber
      density during pathological conditions. We have investigated changes in epidermal
      nerve fiber density in three different rat models that selectively produce
      chronic itch (the dry skin model), or itch and inflammation (the dermatitis
      model), or chronic inflammation without itch (the CFA model). In the epidermis,
      we identified peptidergic fibers-that is, immunoreactive (IR) for calcitonin gene
      related peptide or substance P-and non-peptidergic fibers-that is, IR for P2X3.
      The overall density of nerve fibers was determined using IR for the protein gene
      product 9.5. In all three models, the density of epidermal peptidergic nerve
      fibers increased up to five times when compared with a sham-treated control
      group. In contrast, the density of epidermal non-peptidergic fibers was not
      increased, except for a small but significant increase in the dry skin model.
      Chronic inflammation showed an increased density of peptidergic fibers without
      itch, indicating that increased nerve fiber density is not invariably associated
      with itch. The finding that different types of skin pathology induced
      differential changes in nerve fiber density may be used as a diagnostic tool in
      humans, through skin biopsies, to identify different types of pathology and to
      monitor the effect of therapies.

PMID- 25848981
TI  - RNA-seq analysis of short fiber mutants Ligon-lintless-1 (Li 1 ) and - 2 (Li 2 )
      revealed important role of aquaporins in cotton (Gossypium hirsutum L.) fiber
      elongation.
AB  - BACKGROUND: Cotton fiber length is a key determinant of fiber quality for the
      textile industry. Understanding the molecular basis of fiber elongation would
      provide a means for improvement of fiber length. Ligon lintless-1 (Li 1 ) and
      Ligon lintless-2 (Li 2 ) are monogenic and dominant mutations, that result in an
      extreme reduction in the length of lint fiber to approximately 6 mm on mature
      seeds. In a near-isogenic state with wild type (WT) cotton these two short fiber
      mutants provide an excellent model system to study mechanisms of fiber
      elongation. RESULTS: We used next generation sequencing (RNA-seq) to identify
      common fiber elongation related genes in developing fibers of Li 1 and Li 2
      mutants growing in the field and a greenhouse. We found a large number of
      differentially expressed genes common to both mutants, including 531 up-regulated
      genes and 652 down-regulated genes. Major intrinsic proteins or aquaporins were
      one of the most significantly over-represented gene families among common down
      regulated genes in Li 1 and Li 2 fibers. The members of three subfamilies of
      aquaporins, including plasma membrane intrinsic proteins, tonoplast intrinsic
      proteins and NOD26-like intrinsic proteins were down-regulated in short fiber
      mutants. The osmotic concentration and the concentrations of soluble sugars were
      lower in fiber cells of both short fiber mutants than in WT, whereas the
      concentrations of K+ and malic acid were significantly higher in mutants during
      rapid cell elongation. CONCLUSIONS: We found that the aquaporins were the most
      down-regulated gene family in both short fiber mutants. The osmolality and
      concentrations of soluble sugars were less in saps of Li 1 - Li 2 , whereas the
      concentrations of malic acid, K+ and other detected ions were significantly
      higher in saps of mutants than in WT. These results suggest that higher
      accumulation of ions in fiber cells, reduced osmotic pressure and low expression
      of aquaporins, may contribute to the cessation of fiber elongation in Li 1 and Li
      2 short-fiber mutants. The research presented here provides new insights into
      osmoregulation of short fiber mutants and the role of aquaporins in cotton fiber
      elongation.

PMID- 25848980
TI  - IQGAP1 and IQGAP3 Serve Individually Essential Roles in Normal Epidermal
      Homeostasis and Tumor Progression.
AB  - IQ motif-containing GTPase-activating protein (IQGAP) scaffolding proteins
      regulate many essential cellular processes including growth factor receptor
      signaling, cytoskeletal rearrangement, adhesion, and proliferation and are highly
      expressed in many cancers. Using genetically engineered human skin tissue in
      vivo, we demonstrate that diminished, sub-physiologic expression of IQGAP1 or
      IQGAP3 is sufficient to maintain normal epidermal homeostasis, whereas
      significantly higher levels are required to support tumorigenesis. To target this
      tumor-specific IQGAP requirement in vivo, we engineered epidermal keratinocytes
      to express individual IQGAP protein domains designed to compete with endogenous
      IQGAPs for effector protein binding. Expression of the IQGAP1-IQ motif decoy
      domain in epidermal tissue in vivo inhibits oncogenic Ras-driven mitogen
      activated protein kinase signaling and antagonizes tumorigenesis, without
      disrupting normal epidermal proliferation or differentiation. These findings
      define essential non-redundant roles for IQGAP1 and IQGAP3 in the epidermis and
      demonstrate the potential of IQGAP antagonism for cancer therapy. 

PMID- 25848982
TI  - Mammary gland tumor promotion by chronic administration of IGF1 and the insulin
      analogue AspB10 in the p53R270H/+WAPCre mouse model.
AB  - INTRODUCTION: Insulin analogues are structurally modified molecules with altered
      pharmaco-kinetic and -dynamic properties compared to regular human insulin used
      by diabetic patients. While these compounds are tested for undesired mitogenic
      effects, an epidemiological discussion is ongoing regarding an association
      between insulin analogue therapy and increased cancer incidence, including breast
      cancer. Standard in vivo rodent carcinogenesis assays do not pick up this
      possible increased carcinogenic potential. METHODS: Here we studied the role of
      insulin analogues in breast cancer development. For this we used the human
      relevant mammary gland specific p53R270H/+WAPCre mouse model. Animals received
      life long repeated treatment with four different insulin (-like) molecules:
      normal insulin, insulin glargine, insulin X10 (AspB10) or insulin-like growth
      factor 1 (IGF1). RESULTS: Insulin-like molecules with strong mitogenic signaling,
      insulin X10 and IGF1, significantly decreased the time for tumor development.
      Yet, insulin glargine and normal insulin, did not significantly decrease the
      latency time for (mammary gland) tumor development. The majority of tumors had an
      epithelial to mesenchymal transition phenotype (EMT), irrespective of treatment
      condition. Enhanced extracellular signaling related kinase (Erk) or
      serine/threonine kinase (Akt) mitogenic signaling was in particular present in
      tumors from the insulin X10 and IGF1 treatment groups. CONCLUSIONS: These data
      indicate that insulin-like molecules with enhanced mitogenic signaling increase
      the risk of breast cancer development. Moreover, the use of a tissue specific
      cancer model, like the p53R270H/+WAPCre mouse model, is relevant to assess the
      intrinsic pro-carcinogenic potential of mitogenic and non-mitogenic biologicals
      such as insulin analogues.

PMID- 25848983
TI  - Functionalized iron oxide nanoparticles for controlling the movement of immune
      cells.
AB  - Immunotherapy is currently being investigated for the treatment of many diseases,
      including cancer. The ability to control the location of immune cells during or
      following activation would represent a powerful new technique for this field.
      Targeted magnetic delivery is emerging as a technique for controlling cell
      movement and localization. Here we show that this technique can be extended to
      microglia, the primary phagocytic immune cells in the central nervous system. The
      magnetized microglia were generated by loading the cells with iron oxide
      nanoparticles functionalized with CpG oligonucleotides, serving as a proof of
      principle that nanoparticles can be used to both deliver an immunostimulatory
      cargo to cells and to control the movement of the cells. The nanoparticle
      oligonucleotide conjugates are efficiently internalized, non-toxic, and
      immunostimulatory. We demonstrate that the in vitro migration of the adherent,
      loaded microglia can be controlled by an external magnetic field and that
      magnetically-induced migration is non-cytotoxic. In order to capture video of
      this magnetically-induced migration of loaded cells, a novel 3D-printed "cell
      box" was designed to facilitate our imaging application. Analysis of cell
      movement velocities clearly demonstrate increased cell velocities toward the
      magnet. These studies represent the initial step towards our final goal of using
      nanoparticles to both activate immune cells and to control their trafficking
      within the diseased brain. 

PMID- 25848984
TI  - A Bivalent, Chimeric Rabies Virus Expressing Simian Immunodeficiency Virus
      Envelope Induces Multifunctional Antibody Responses.
AB  - We previously showed that a matrix (M) gene-deleted rabies virus (RABV)-based
      vaccine (RABV-DeltaM) is highly immunogenic and induces potent B cell responses
      in the context of RABV infection. We speculated that RABV-DeltaM expressing HIV
      proteins would also induce potent B cell responses against HIV antigens. As a
      prerequisite to future studies in nonhuman primates, we completed immunogenicity
      studies in mice to confirm the ability of RABV-DeltaM to induce polyfunctional B
      cell responses in the context of HIV. To that end, the envelope protein from the
      mac239 strain of SIV (SIVmac239Env) was cloned into RABV-DeltaM, resulting in
      RABV-DeltaM-Env. Infectious virus was recovered following standard methods and
      propagated on baby hamster kidney cells stably expressing RABV M [>10(7) focus
      forming units (ffu)/ml]. Western blot analysis of cell lysates or of purified
      virions confirmed Env expression on the surface of infected cells and within
      virus particles, respectively. Positive neutralization activity against a
      neutralization-sensitive SIV strain and to a lesser extent against a
      neutralization-resistant SIV strain was detected in mice after a single
      intramuscular inoculation with RABV-DeltaM-Env. The quality, but not quantity, of
      the antibody response was enhanced via boosting with recombinant gp130 or RABV
      DeltaM-Env as measured by an increase in antibody avidity and a skewing toward a
      Th1-type antibody response. We also show that an intradermal inoculation induces
      higher antibodies than an intramuscular or intranasal inoculation. An intradermal
      inoculation of RABV-DeltaM-Env followed by a boost inoculation with recombinant
      gp130 produced anti-SIV antibodies with neutralizing and nonneutralizing antibody
      (nNAb) effector functions. Together, RABV-DeltaM-Env induces B cells to secrete
      antibodies against SIV with the potential to clear both "free" and cell
      associated virus. Strategies capable of eliciting both NAbs as well as nNAbs
      might help to improve the efficacy of HIV-1 vaccines. 

PMID- 25848985
TI  - Understanding the contribution of native tracheobronchial structure to lung
      function: CT assessment of airway morphology in never smokers.
AB  - BACKGROUND: Computed tomographic (CT) airway lumen narrowing is associated with
      lower lung function. Although volumetric CT measures of airways (wall volume [WV]
      and lumen volume [LV]) compared to cross sectional measures can more accurately
      reflect bronchial morphology, data of their use in never smokers is scarce. We
      hypothesize that native tracheobronchial tree morphology as assessed by
      volumetric CT metrics play a significant role in determining lung function in
      normal subjects. We aimed to assess the relationships between airway size, the
      projected branching generation number (BGN) to reach airways of <2mm lumen
      diameter -the site for airflow obstruction in smokers- and measures of lung
      function including forced expiratory volume in 1 second (FEV1) and forced
      expiratory flow between 25% and 75% of vital capacity (FEF 25-75). METHODS: We
      assessed WV and LV of segmental and subsegmental airways from six bronchial paths
      as well as lung volume on CT scans from 106 never smokers. We calculated the
      lumen area ratio of the subsegmental to segmental airways and estimated the
      projected BGN to reach a <2mm-lumen-diameter airway assuming a dichotomized
      tracheobronchial tree model. Regression analysis was used to assess the
      relationships between airway size, BGN, FEF 25-75, and FEV1. RESULTS: We found
      that in models adjusted for demographics, LV and WV of segmental and subsegmental
      airways were directly related to FEV1 (P <0.05 for all the models). In adjusted
      models for age, sex, race, LV and lung volume or height, the projected BGN was
      directly associated with FEF 25-75 and FEV1 (P = 0.001) where subjects with lower
      FEV1 had fewer calculated branch generations between the subsegmental bronchus
      and small airways. There was no association between airway lumen area ratio and
      lung volume. CONCLUSION: We conclude that in never smokers, those with smaller
      central airways had lower airflow and those with lower airflow had less parallel
      airway pathways independent of lung size. These findings suggest that variability
      in the structure of the tracheobronchial tree may influence the risk of
      developing clinically relevant smoking related airway obstruction.

PMID- 25848987
TI  - Complete genome sequence of the lipase producing strain Burkholderia glumae PG1.
AB  - The Gram-negative proteobacterium Burkholderia glumae PG1 produces a lipase of
      biotechnological interest, which is used for the production of enantiopure
      pharmaceuticals. In order to better understand the underlying mechanisms and
      provide a basis for further studies, we present here the complete genome sequence
      of B. glumae PG1. 

PMID- 25848986
TI  - Convergence and extrusion are required for normal fusion of the mammalian
      secondary palate.
AB  - The fusion of two distinct prominences into one continuous structure is common
      during development and typically requires integration of two epithelia and
      subsequent removal of that intervening epithelium. Using confocal live imaging,
      we directly observed the cellular processes underlying tissue fusion, using the
      secondary palatal shelves as a model. We find that convergence of a multi-layered
      epithelium into a single-layer epithelium is an essential early step, driven by
      cell intercalation, and is concurrent to orthogonal cell displacement and
      epithelial cell extrusion. Functional studies in mice indicate that this process
      requires an actomyosin contractility pathway involving Rho kinase (ROCK) and
      myosin light chain kinase (MLCK), culminating in the activation of non-muscle
      myosin IIA (NMIIA). Together, these data indicate that actomyosin contractility
      drives cell intercalation and cell extrusion during palate fusion and suggest a
      general mechanism for tissue fusion in development. 

PMID- 25848988
TI  - Complete genome sequence of oxalate-degrading bacterium Pandoraea vervacti DSM
      23571(T).
AB  - Pandoraea vervacti DSM 23571(T) is an oxalate metabolizing bacterium isolated
      from an uncultivated field soil in Mugla, Turkey. Here, we present the first
      complete genome sequence of P. vervacti DSM 23571(T). A complete pathway for
      degradation of oxalate was revealed from the genome analysis. These data are
      important to path new opportunities for genetic engineering in the field of
      biotechnology. 

PMID- 25848989
TI  - Targeted gene mutation in tetraploid potato through transient TALEN expression in
      protoplasts.
AB  - Potato is the third largest food crop in the world, however, the high degree of
      heterozygosity, the tetrasomic inheritance and severe inbreeding depression are
      major difficulties for conventional potato breeding. The rapid development of
      modern breeding methods offers new possibilities to enhance breeding efficiency
      and precise improvement of desirable traits. New site-directed mutagenesis
      techniques that can directly edit the target genes without any integration of
      recombinant DNA are especially favorable. Here we present a successful pipeline
      for site-directed mutagenesis in tetraploid potato through transient TALEN
      expression in protoplasts. The transfection efficiency of protoplasts was 38-39%
      and the site-directed mutation frequency was 7-8% with a few base deletions as
      the predominant type of mutation. Among the protoplast-derived calli, 11-13%
      showed mutations and a similar frequency (10%) was observed in the regenerated
      shoots. Our results indicate that the site-directed mutagenesis technology could
      be used as a new breeding method in potato as well as for functional analysis of
      important genes to promote sustainable potato production. 

PMID- 25848990
TI  - Reducing the infant mortality rate of India to 20 by 2020: together we can do.

PMID- 25848991
TI  - Building capacity of Indian scientists to conduct systematic reviews in child
      health: an ICMR initiative.
AB  - Knowledge and training in evidence-based medicine is essential for informed
      clinical decision-making and treatment choices. Systematic reviews identify,
      appraise and synthesize research-based evidence and present it in accessible
      format. The Indian Council of Medical Research has promoted evidence-based
      medicine in India by establishing an Advanced Center for evidence based medicine
      that hosted the South Asian Cochrane Network and Center at the Christian Medical
      College, Vellore; procuring a national subscription to The Cochrane Library
      making it accessible to all Indian scientists; and establishing a Center for
      Advanced research on evidence- based child health at Post Graduate Institute of
      Medical Education and Research, Chandigarh. This article informs about a national
      level initiative by ICMR that aims to harness the translational potential of
      secondary research, by funding systematic reviews aligned to national health
      priorities selected through a national competitive process; and to provide
      training, mentoring, and quality assurance. A continuing scheme of funding high
      quality systematic reviews on priority areas of Child Health may follow. 

PMID- 25848992
TI  - The remaining challenges to laboratory-based surveillance of invasive
      pneumococcal disease.

PMID- 25848993
TI  - Invasive pneumococcal disease and India.

PMID- 25848994
TI  - Stress: a modifiable factor in the etiology of adolescent depression.

PMID- 25848995
TI  - Hospital-based surveillance of invasive pneumococcal disease and pneumonia in
      South Bangalore, India.
AB  - OBJECTIVE: To estimate the incidence of invasive pneumococcal disease and
      pneumonia, distribution of pneumococcal serotypes, and antibiotic susceptibility
      in children aged 28 days to <60 months. DESIGN: Hospital-based surveillance.
      SETTING: South Bangalore, India. PARTICIPANTS: 9950 children aged 28 days to <60
      months with clinical suspicion of invasive pneumococcal disease or pneumonia.
      RESULTS: The estimated at-risk population included 224,966 children <5 years of
      age. Forty cases of invasive pneumococcal disease were identified. Estimated
      invasive pneumococcal disease incidence was 17.8/100,000 with incidence being
      highest among children aged 6 months to <12 months (49.9/100,000). Clinical
      pneumonia syndrome was the most frequent diagnosis (12.5/100,000). Pneumococcal
      serotypes included: 6A (n=6, 16.7%); 14 (n=5, 13.9%); 5 (n=4, 11.1%); 6B (n=4,
      11.1%); 1, 18C, and 19A (n=3 each, 8.3%); 9V (n=2, 5.6%); and 3, 4, 10C, 18A,
      18F, and 19F (n=1 each, 2.8%). Serotypes 6A, 14, 6B, 1, 18C, 19A, 9V, 4, 10C, and
      18A showed antibiotic resistance. Clinical pneumonia incidence was 2109/100,000,
      with incidence being highest among children aged 28 days to <6 months
      (5033/100,000). Chest radiograph-confirmed pneumonia incidence was 1114/100,000,
      with incidence being highest among children aged 28 days to <6 months
      (2413/100,000). CONCLUSIONS: Invasive pneumococcal disease and pneumonia were
      found to be common causes of morbidity in young children living in South
      Bangalore, India.

PMID- 25848996
TI  - Diagnostic accuracy of Indian Scale for Assessment of Autism (ISAA) in chidren
      aged 2-9 years.
AB  - OBJECTIVE: To determine the diagnostic accuracy of Indian Scale for Assessment of
      Autism (ISAA) in children aged 2-9 year at high risk of autism, and to ascertain
      the level of agreement with Childhood Autism Rating Scale (CARS). DESIGN:
      Diagnostic Accuracy study. SETTING: Tertiary-level hospital. PARTICIPANTS:
      Children aged between 2 and 9 year and considered to be at a high risk for autism
      (delayed development, and age-inappropriate cognition, speech, social
      interaction, behavior or play) were recruited. Those with diagnosed Hearing
      impairment, Cerebral palsy, Attention deficit hyperactivity disorder or Pervasive
      developmental disorders (PDD) were excluded. METHODS: Eligible children underwent
      a comprehensive assessment by an expert. The study group comprising of PDD,
      Global developmental delay (GDD) or Intellectual disability was administered ISAA
      by an investigator after one week. Both evaluators were blinded. ISAA results
      were compared to the Experts diagnosis and CARS scores. RESULTS: Out of 102
      eligible children, 90 formed the study group (63 males, mean age 4.5y). ISAA had
      a sensitivity 93.3, specificity of 97.4, positive and negative likelihood ratios
      85.7 and 98.7 and positive and negative predictive values of 35.5 and 0.08,
      respectively. Reliability was good and validity sub-optimal (r low, in 4/6
      domains). The optimal threshold point demarcating Autism from No autism according
      to Receiver Operating Characteristic curve was ISAA score of 70. Level of
      agreement with CARS measured by Kappa coefficient was low (0.14). CONCLUSIONS:
      The role of ISAA in 3-9 year old children at high risk for Autism is limited to
      identifying and certifying Autism at ISAA score of 70. It requires re-examination
      in 2-3 year olds.

PMID- 25848997
TI  - Academic stress and depression among adolescents: a cross-sectional study.
AB  - OBJECTIVE: To examine the relationship between academic stress and depression
      among adolescents. METHODS: A cross-sectional study was conducted at higher
      secondary schools in Tamil Nadu. 1120 adolescents were included in the study
      after screening by MINI-kid tool. Modified Educatonal Stress Scale for
      Adolescents was administered to all children. RESULTS: Adolescents who had
      academic stress were at 2.4 times (95% CI=0.9-2.4) (P<0.001) higher risk of
      depression than adolescents without academic stress. CONCLUSIONS: Adolescents
      with severe academic stress need to be identified early as interventions to
      reduce academic stress is likely to affect the occurrence and severity of
      depression.

PMID- 25848998
TI  - Serum IgG and IgA levels in polio and non-polio acute flaccid paralysis cases in
      western Uttar Pradesh, India.
AB  - OBJECTIVE: IgG and IgA immunocompetence of children with wild poliovirus
      poliomyelitis and non-polio acute flaccid paralysis. METHODS: 932 cases of acute
      flaccid paralysis, reported in 2008-2009, were tested for presence of polio and
      non-polio enteroviruses according to the WHO standards. Serum IgA and IgG levels
      were determined by sandwich ELISA. RESULTS: Mean (SD) IgA levels [0.87 (0.62)g/L;
      n=28] of virologically confirmed poliomyelitis cases were lower than those of
      virus negative [1.21 (0.83)g/L; n=612] and non-polio Enterovirus positive [1.22
      (0.79)g/L; n=240] cases of acute flaccid paralysis. No significant difference was
      observed in the concentration of IgG among these groups. CONCLUSIONS: IgA plays
      an important role in protection against poliomyelitis.

PMID- 25848999
TI  - Acute kidney injury in children after cardiopulmonary bypass: risk factors and
      outcome.
AB  - OBJECTIVE: To determine the incidence, risk factors and outcomes of acute kidney
      injury in children undergoing cardiac surgery for congenital heart disease.
      METHODS: We enrolled 208 patients undergoing cardiac surgery for congenital heart
      disease during January 2012 to March 2013. Acute kidney injury was defined as per
      Acute Kidney Injury Network criteria. RESULTS: Twenty patients had Acute kidney
      injury; 14 were infants. Age <1 yr, cardiopulmonary bypass time, prolonged
      ventilator requirement, pump failure, sepsis and hematological complications were
      identified as independent risk factors for any degree for acute kidney injury.
      All patients with acute kidney injury recovered the kidney function at the time
      of discharge. CONCLUSIONS: Acute kidney injury is common in children after
      cardiac surgery, especially in infants.

PMID- 25849000
TI  - Surfactant replacement therapy in extremely low gestational age newborns.
AB  - There is a growing body of evidence over the last years suggesting continuous
      positive airway pressure (CPAP) ventilation being the first choice of ventilatory
      support in newborns with extremely low gestational age, and early rescue
      surfactant treatment being as effective as prophylactic therapy. The Intubation
      Surfactant Extubation procedure is discussed as an alternative procedure that may
      have the potential to combine the positive effects of surfactant and early CPAP.
      A further mode of surfactant administration, administration via a thin
      endotracheal catheter during spontaneous breathing with CPAP, has recently come
      into clinical use. This less invasive surfactant administration technique shows
      some short-term benefits but still cannot be recommended for general use in this
      vulnerable population. Long-term follow-up studies are needed to allow new
      recommendations on surfactant therapy in this high-risk population. 

PMID- 25849001
TI  - Portfolio-based learning and assessment.
AB  - Assessment using portfolios has recently gained wider acceptance, and is being
      considered relevant to several educational aspects in medicine, including
      formative and summative assessment during resident training, revalidation and
      continuing professional development. In this article, we provide an overview of
      the use of portfolio as an assessment and learning tool. We have discussed the
      rationale of using portfolio in medical education, its advantages and criticisms,
      and some of the associated challenges and dilemmas. 

PMID- 25849002
TI  - Tetravalent dengue vaccine for children: evidence-based-medicine viewpoint.

PMID- 25849003
TI  - Tetravalent dengue vaccine for children: vaccinologists viewpoint.

PMID- 25849004
TI  - Tetravalent dengue vaccine for children: pediatricians viewpoint.

PMID- 25849005
TI  - Primary lung abscess in early infancy.
AB  - BACKGROUND: Lung abscess is rare in early infancy. CASE CHARACTERISTICS: We
      report two infants with lung abscess, who presented with short respiratory
      llness. INTERVENTION: Infants were managed with broad spectrum antibiotics
      including Clindamycin. Needle aspiration was attempted in one case. MESSAGE: High
      index of suspicion in infants with respiratory distress of prolonged duration can
      help in reaching the diagnosis.

PMID- 25849006
TI  - Limb girdle weakness responding to salbutamol: an Indian family with DOK7
      mutation.
AB  - BACKGROUND: Congenital Myasthenic Syndromes (CMS) are heterogeneous genetic
      diseases. CASE CHARACTERISTICS: Two siblings presented with progressive limb
      girdle weakness without significant fluctuations or ocular muscle weakness.
      Repetitive nerve stimulation showed a decremental response and there was no
      response to pyridostigmine therapy. OUTCOME: A trial of salbutamol produced a
      remarkable, consistent improvement. Mutation in exon 5 of the DOK7 gene was found
      in both siblings. MESSAGE: Patients with congenital myasthenic syndrome with DOK
      7 mutation benefit remarkably with salbutamol.

PMID- 25849007
TI  - Kawasaki disease with autoimmune hemolytic anemia.
AB  - BACKGROUND: Association of autoimmune haemolytic anaemia has been seldom reported
      with Kawasaki disease. CASE CHARACTERISTICS: A 7-month-old boy, presented with
      prolonged fever, erythematous rash, severe pallor and hepatosplenomegaly.
      OBSERVATIONS: Positive Direct Coombs test and coronary artery aneurysm on
      echocardiography. He was managed with steroids along with intravenous
      immunoglobulins and aspirin. OUTCOME: Early identification of the condition
      helped in the management. MESSAGE: Patients of autoimmune hemolytic anemia with
      unusual features such as prolonged fever, skin rash, and mixed antibody response
      in Coombs test should be evaluated for underlying Kawasaki disease as a possible
      etiology.

PMID- 25849008
TI  - Let the life go on.

PMID- 25849009
TI  - Infantile tremor syndrome -- down but not out.
AB  - Retrospective chart review of 21 infants with infantile tremor syndrome for
      vitamin B12 deficiency showed low serum vitamin B12 levels in 8/16 (50%). Of the
      eight infants with normal levels, six had received vitamin B12 before referral.
      Macrocytosis and low maternal serum B12 was found in 12 and seven cases each.
      Treatment with vitamin B12 alone produced rapid recovery. 

PMID- 25849010
TI  - Impact of house-hold food insecurity on nutritional status of HIV-infected
      children attending an ART centre in Tamil Nadu.
AB  - We studied the level of food insecurity among households with HIV-infected
      children and its relationship with childhood nutritional indicators. Among the
      147 children assessed, food insecurity was present in 59% of households. Majority
      of children with stunting belonged to-food insecure families. Stunting and
      Underweight were more prevalent among children >5 years of age. 

PMID- 25849011
TI  - Knowledge and attitude of health researchers from India towards paying to publish
      and open access journals.
AB  - Knowledge and attitude of 2509 Indian health researchers towards open access
      publishing and authors paying to publish model was evaluated. 55.6% researchers
      had knowledge about open access and 76% about Author pay model. 72% of
      Researchers were not interested to pay publication charges. Lack of research
      grants were the primary reason for inability to pay publication charges. 

PMID- 25849012
TI  - Heliox use in ventilation of preterms.

PMID- 25849013
TI  - Heliox use in ventilaion of newborns: authors reply.

PMID- 25849014
TI  - Immunization recommendations should not be ambiguous.

PMID- 25849015
TI  - IAP immunization guidelines: authors reply.

PMID- 25849016
TI  - Listen to mother first.

PMID- 25849017
TI  - Listen to mother first: reply.

PMID- 25849018
TI  - The Peshawar peril.

PMID- 25849019
TI  - Treatment guidelines for seasonal influenza: need for a rethink.

PMID- 25849020
TI  - Localised gigantism.

PMID- 25849021
TI  - Nevus lipomatosus cutaneous superficialis.

PMID- 25849022
TI  - Fordyce's spots.

PMID- 25849023
TI  - Chiral methyl-branched pheromones.
AB  - Insect pheromones are some of the most interesting natural products because they
      are utilized for interspecific communication between various insects, such as
      beetles, moths, ants, and cockroaches. A large number of compounds of many kinds
      have been identified as pheromone components, reflecting the diversity of insect
      species. While this review deals only with chiral methyl-branched pheromones, the
      chemical structures of more than one hundred non-terpene compounds have been
      determined by applying excellent analytical techniques. Furthermore, their
      stereoselective syntheses have been achieved by employing trustworthy chiral
      sources and ingenious enantioselective reactions. The information has been
      reviewed here not only to make them available for new research but also to
      understand the characteristic chemical structures of the chiral pheromones. Since
      biosynthetic studies are still limited, it might be meaningful to examine whether
      the structures, particularly the positions and configurations of the branched
      methyl groups, are correlated with the taxonomy of the pheromone producers and
      also with the function of the pheromones in communication systems.

PMID- 25849025
TI  - Correction: research blogging: indexing and registering the change in science
      2.0.

PMID- 25849024
TI  - A case-control analysis of oral contraceptive use and breast cancer subtypes in
      the African American Breast Cancer Epidemiology and Risk Consortium.
AB  - INTRODUCTION: Recent oral contraceptive (OC) use has been consistently associated
      with increased risk of breast cancer, but evidence on specific breast cancer
      subtypes is sparse. METHODS: We investigated recency and duration of OC use in
      relation to molecular subtypes of breast cancer in a pooled analysis of data from
      the African American Breast Cancer Epidemiology and Risk Consortium. The study
      included 1,848 women with estrogen receptor-positive (ER+) breast cancer, 1,043
      with ER-negative (ER-) breast cancer (including 494 triple negative (TN) tumors,
      which do not have receptors for estrogen, progesterone, and human epidermal
      growth factor 2), and 10,044 controls. Multivariable polytomous logistic
      regression models were used to estimate odds ratios (ORs) and 95% confidence
      intervals (CIs) for exposure categories relative to never use, controlling for
      potential confounding variables. RESULTS: OC use within the previous 5 years was
      associated with increased risk of ER+ (OR 1.46, 95% CI 1.18 to 1.81), ER- (OR
      1.57, 95% CI 1.22 to 1.43), and TN (OR 1.78, 95% CI 1.25 to 2.53) breast cancer.
      The risk declined after cessation of use but was apparent for ER+ cancer for 15
      to 19 years after cessation and for ER- breast cancer for an even longer interval
      after cessation. Long duration of use was also associated with increased risk of
      each subtype, particularly ER-. CONCLUSIONS: Our results suggest that OC use,
      particularly recent use of long duration, is associated with an increased risk of
      ER+, ER-, and TN breast cancer in African American women. Research into
      mechanisms that explain these findings, especially the association with ER-
      breast cancer, is needed.

PMID- 25849026
TI  - Chlorogenic acid improves late diabetes through adiponectin receptor signaling
      pathways in db/db mice.
AB  - The aim of this study was to examine the effects of chlorogenic acid (CGA) on
      glucose and lipid metabolism in late diabetic db/db mice, as well as on
      adiponectin receptors and their signaling molecules, to provide evidence for CGA
      in the prevention of type 2 diabetes. We randomly divided 16 female db/db mice
      into db/db-CGA and db/db-control (CON) groups equally; db/m mice were used as
      control mice. The mice in both the db/db-CGA and db/m-CGA groups were
      administered 80 mg/kg/d CGA by lavage for 12 weeks, whereas the mice in both CON
      groups were given equal volumes of phosphate-buffered saline (PBS) by lavage. At
      the end of the intervention, we assessed body fat and the parameters of glucose
      and lipid metabolism in the plasma, liver and skeletal muscle tissues as well as
      the levels of aldose reductase (AR) and transforming growth factor-beta1 (TGF
      beta1) in the kidneys and measured adiponectin receptors and the protein
      expression of their signaling molecules in liver and muscle tissues. After 12
      weeks of intervention, compared with the db/db-CON group, the percentage of body
      fat, fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c) in the
      db/db-CGA group were all significantly decreased; TGF-beta1 protein expression
      and AR activity in the kidney were both decreased; and the adiponectin level in
      visceral adipose was increased. The protein expression of adiponectin receptors
      (ADPNRs), the phosphorylation of AMP-activated protein kinase (AMPK) in the liver
      and muscle, and the mRNA and protein levels of peroxisome proliferator-activated
      receptor alpha (PPAR-alpha) in the liver were all significantly greater. CGA
      could lower the levels of fasting plasma glucose and HbA1c during late diabetes
      and improve kidney fibrosis to some extent through the modulation of adiponectin
      receptor signaling pathways in db/db mice. 

PMID- 25849027
TI  - Hydroethanolic Pistacia atlantica hulls extract improved wound healing process;
      evidence for mast cells infiltration, angiogenesis and RNA stability.
AB  - In Iranian traditional therapy folk, the Pistacia is used for treatment of wound
      inflammation. Here in the present study, the In vivo effect of Pistacia atlantica
      hulls ointment (PAO) on the wound healing process was assessed. Excision and
      incision wounds were induced in rats. Three different doses of PAO were
      administrated. Following 3, 7, 14 and 21 days, the tissue samples were obtained
      and skin irritation ratio, hydroxyproline content, as well as immune cells,
      fibroblasts, fibrocytes distribution and collagen density were analyzed.
      Moreover, the cellular RNA damage examined using epi-fluorescent microscope.
      Hydroethanolic extract of PAO significantly (P < 0.05) increased wound
      contraction percentage and up-regulated hydroxyproline content. The animals in
      medium and high dose PAO-treated groups exhibited remarkably (P < 0.05) higher
      fibroblast distribution and significantly (P < 0.05) lower immune cells
      infiltration. PAO up-regulated mast cells distribution on day 7 and elevated
      neovascularization in a dose dependent manner. Significantly lower RNA damage was
      revealed in PAO-treated animals. Our data showed that, PAO shortened the
      inflammation phase by provoking the fibroblast proliferation. Moreover, PAO
      enhanced mast cells distribution and infiltration, which in turn promoted the
      neovascularization. Ultimately, promoted angiogenesis increased RNA stability in
      different cell types. Thus, Hydroethanolic extract of PAO can be considered as an
      appropriate compound for wound healing medicine. 

PMID- 25849028
TI  - The Potential of Canna lily for Wastewater Treatment Under Indian Conditions.
AB  - Low cost treatment of polluted wastewater has become a serious challenge in most
      of the urban areas of developing countries. The present study was undertaken to
      investigate the potential of Canna lily towards removal of carbon, nitrogen, and
      phosphorus from wastewater under sub-tropical conditions. A constructed wetland
      (CW) cell supporting vegetative layer of Canna lily was used to treat wastewater
      having high strength of CNP. Removal of biological oxygen demand (BOD3) and
      chemical oxygen demand (COD) varied between 69.8-96.4% and 63.6-99.1%,
      respectively. C. lily could efficiently remove carbon from a difficult to degrade
      wastewater at COD:BOD ratio of 24.4. Simultaneous reduction in TKN and nitrate
      pointed to good nitrification rates, and efficient plant assimilation as the
      dominant nutrient removal mechanism in the present study. Suitable Indian agro
      climatic conditions favored plant growth and no evident stress over the Canna
      plant was observed. High removal rate of 809.8 mg/m(2)-day for TKN, 15.0 mg/m(2)
      day for nitrate, and 164.2 mg/m(2)-day for phosphate suggests for a possible use
      of Canna-based CW for wastewater treatment for small, rural, and remote Indian
      communities.

PMID- 25849029
TI  - Landscape variation in tree species richness in northern Iran forests.
AB  - Mapping landscape variation in tree species richness (SR) is essential to the
      long term management and conservation of forest ecosystems. The current study
      examines the prospect of mapping field assessments of SR in a high-elevation,
      deciduous forest in northern Iran as a function of 16 biophysical variables
      representative of the area's unique physiography, including topography and
      coastal placement, biophysical environment, and forests. Basic to this study is
      the development of moderate-resolution biophysical surfaces and associated plot
      estimates for 202 permanent sampling plots. The biophysical variables include:
      (i) three topographic variables generated directly from the area's digital
      terrain model; (ii) four ecophysiologically-relevant variables derived from
      process models or from first principles; and (iii) seven variables of Landsat-8
      acquired surface reflectance and two, of surface radiance. With symbolic
      regression, it was shown that only four of the 16 variables were needed to
      explain 85% of observed plot-level variation in SR (i.e., wind velocity, surface
      reflectance of blue light, and topographic wetness indices representative of soil
      water content), yielding mean-absolute and root-mean-squared error of 0.50 and
      0.78, respectively. Overall, localised calculations of wind velocity and surface
      reflectance of blue light explained about 63% of observed variation in SR, with
      wind velocity accounting for 51% of that variation. The remaining 22% was
      explained by linear combinations of soil-water-related topographic indices and
      associated thresholds. In general, SR and diversity tended to be greatest for
      plots dominated by Carpinus betulus (involving >= 33% of all trees in a plot),
      than by Fagus orientalis (median difference of one species). This study provides
      a significant step towards describing landscape variation in SR as a function of
      modelled and satellite-based information and symbolic regression. Methods in this
      study are sufficiently general to be applicable to the characterisation of SR in
      other forested regions of the world, providing plot-scale data are available for
      model generation. 

PMID- 25849030
TI  - The role of CD95 and CD95 ligand in cancer.

PMID- 25849031
TI  - Proteolysis of virulence regulator ToxR is associated with entry of Vibrio
      cholerae into a dormant state.
AB  - Vibrio cholerae O1 is a natural inhabitant of aquatic environments and causes the
      diarrheal disease, cholera. Two of its primary virulence regulators, TcpP and
      ToxR, are localized in the inner membrane. TcpP is encoded on the Vibrio
      Pathogenicity Island (VPI), a horizontally acquired mobile genetic element, and
      functions primarily in virulence gene regulation. TcpP has been shown to undergo
      regulated intramembrane proteolysis (RIP) in response to environmental conditions
      that are unfavorable for virulence gene expression. ToxR is encoded in the
      ancestral genome and is present in non-pathogenic strains of V. cholerae,
      indicating it has roles outside of the human host. In this study, we show that
      ToxR undergoes RIP in V. cholerae in response to nutrient limitation at alkaline
      pH, a condition that occurs during the stationary phase of growth. This process
      involves the site-2 protease RseP (YaeL), and is dependent upon the RpoE-mediated
      periplasmic stress response, as deletion mutants for the genes encoding these two
      proteins cannot proteolyze ToxR under nutrient limitation at alkaline pH. We
      determined that the loss of ToxR, genetically or by proteolysis, is associated
      with entry of V. cholerae into a dormant state in which the bacterium is normally
      found in the aquatic environment called viable but nonculturable (VBNC). Strains
      that can proteolyze ToxR, or do not encode it, lose culturability, experience a
      change in morphology associated with cells in VBNC, yet remain viable under
      nutrient limitation at alkaline pH. On the other hand, mutant strains that cannot
      proteolyze ToxR remain culturable and maintain the morphology of cells in an
      active state of growth. Overall, our findings provide a link between the
      proteolysis of a virulence regulator and the entry of a pathogen into an
      environmentally persistent state. 

PMID- 25849032
TI  - Does lower gastrointestinal endoscopy during pregnancy pose a risk for mother and
      child? - a systematic review.
AB  - BACKGROUND: Gastrointestinal endoscopy plays a crucial role in the diagnosis and
      management of gastrointestinal disorders. When endoscopy is indicated during
      pregnancy, concerns about the effects on pregnancy outcome often arise. The aim
      of this study was to assess whether lower gastrointestinal endoscopies (LGEs)
      across all three trimesters of pregnancy affects pregnancy outcomes. METHODS: A
      systematic literature search was performed using Embase (including MEDLINE),
      Medline OvidSP, Cochrane Central Register of Controlled Trials, Web-of-Science,
      Google scholar and Pubmed. All original research articles from 1990 until May
      2014 involving pregnant women who underwent LGE for any indication were included.
      Adverse pregnancy events like spontaneous abortion, preterm birth and fetal
      demise were assessed for a temporal and etiological relation with the LGE.
      RESULTS: In total, 5514 references were screened by two independent reviewers.
      Eighty-two references met the inclusion criteria and were selected. Two
      retrospective, controlled studies, one uncontrolled study and 79 case reports
      were identified. In the three studies, birth outcomes did not differ between
      women undergoing LGE during pregnancy, compared to women that had an indication
      for LGE but in whom LGE was not performed because of pregnancy. In 79 case
      reports, 92 patients are described who underwent 100 LGE's during pregnancy. LGEs
      performed in all trimesters (n = 32, 39 and 29) were both temporally and
      etiologically related to 1, 3 and 2 adverse events, respectively. CONCLUSION:
      Based on the available literature, this review concludes that lower
      gastrointestinal endoscopy during pregnancy is of low risk for mother and child
      in all three trimesters of pregnancy.

PMID- 25849035
TI  - Repulsive van der waals forces self-limit native oxide growth.
AB  - Silicon is one of the most studied materials, yet questions remain unanswered
      about its unusual property of growing a self-limiting native oxide that attains
      its final thickness in a matter of hours yet months later has not grown further.
      For the first time, we have explored this self-limiting growth in terms of
      repulsive van der Waals (vdW) forces generated by the combination of material
      properties inherent to the system. These repulsive forces represent an energy
      barrier preventing additional oxidizing chemicals, mainly oxygen and water, from
      adsorbing on the surface as well as hindering diffusion of those that do adsorb
      toward the interface. We have also proven that this native oxide can be increased
      in thickness at room temperature and without reactive species by changing the
      oxidation environment to one predicted by theory to result in attractive vdW
      forces, thus allowing oxygen/water to interact with the surface more freely. 

PMID- 25849033
TI  - Florbetapir PET, FDG PET, and MRI in Down syndrome individuals with and without
      Alzheimer's dementia.
AB  - INTRODUCTION: Down syndrome (DS) is associated with amyloid b (Ab) deposition.
      METHODS: We characterized imaging measurements of regional fibrillar Ab burden,
      cerebral metabolic rate for glucose (rCMRgl), gray matter volumes (rGMVs), and
      age associations in 5 DS with dementia (DS/AD1), 12 DS without dementia (DS/AD2),
      and 9 normal controls (NCs). RESULTS: There were significant group differences in
      mean standard uptake value ratios (SUVRs) for florbetapir with DS/AD1 having the
      highest, followed by DS/AD2, followed by NC. For [18F]-fluorodeoxyglucose
      positron emission tomography, posterior cingulate rCMRgl in DS/AD1 was
      significantly reduced compared with DS/AD2 and NC. For volumetric magnetic
      resonance imaging (vMRI), hippocampal volumes were significantly reduced for the
      DS/AD1 compared with DS/AD2 and NC. Age-related SUVR increases and rCMRgl
      reductions were greater in DS participants than in NCs. DISCUSSION: DS is
      associated with fibrillar Ab, rCMRgl, and rGMV alterations in the dementia stage
      and before the presence of clinical decline. This study provides a foundation for
      the studies needed to inform treatment and prevention in DS.

PMID- 25849034
TI  - Computable cause-and-effect models of healthy and Alzheimer's disease states and
      their mechanistic differential analysis.
AB  - INTRODUCTION: The discovery and development of new treatments for Alzheimer's
      disease (AD) requires a profound mechanistic understanding of the disease. Here,
      we propose a model-driven approach supporting the systematic identification of
      putative disease mechanisms. METHODS: We have created a model for AD and a
      corresponding model for the normal physiology of neurons using biological
      expression language to systematically model causal and correlative relationships
      between biomolecules, pathways, and clinical readouts. Through model-model
      comparison we identify "chains of causal relationships" that lead to new insights
      into putative disease mechanisms. RESULTS: Using differential analysis of our
      models we identified a new mechanism explaining the effect of amyloid-beta on
      apoptosis via both the neurotrophic tyrosine kinase receptor, type 2 and nerve
      growth factor receptor branches of the neurotrophin signaling pathway. We also
      provide the example of a model-guided interpretation of genetic variation data
      for a comorbidity analysis between AD and type 2 diabetes mellitus. DISCUSSION:
      The two computable, literature-based models introduced here provide a powerful
      framework for the generation and validation of rational, testable hypotheses
      across disease areas.

PMID- 25849036
TI  - Development of a multi-toxin method for investigating the carryover of
      zearalenone, deoxynivalenol and their metabolites into milk of dairy cows.
AB  - A dose-response study was carried out to examine the carryover of zearalenone
      (ZEN), deoxynivalenol (DON) and their metabolites into bovine milk. Therefore, a
      feeding trial with 30 dairy cows fed with three different levels of Fusarium
      (FUS) toxin-contaminated maize was performed. A control group (0.02 mg ZEN kg(-1)
      dry matter (DM) and 0.07 DON kg(-1) DM) was compared with two groups fed
      contaminated diets. The first diet contained 0.33 mg ZEN kg(-1) DM and 2.62 mg
      DON kg(-1) DM (group FUS-50) and the second diet contained 0.66 mg ZEN kg(-1) DM
      and 5.24 mg DON kg(-1) DM (group FUS-100). For milk sample analysis, a new cost
      efficient sample preparation method was developed for the simultaneous
      determination of ZEN, DON and their metabolites. The method comprised the
      separation of the milk fat followed by an SPE clean-up on Oasis HLB and a LC
      MS/MS measurement. The less toxic metabolite de-epoxy-DON had the highest
      detected concentration (5.6 ng ml(-1) milk) in the milk samples obtained from the
      feeding trial. Additionally, ZEN (up to 0.29 ng ml(-1)), alpha-zearalenol (up to
      0.17 ng ml(-1)), beta-zearalenol (up to 0.95 ng ml(-1)) and DON (up to 2.5 ng ml(
      1)) were detected in these samples. The milk toxin concentrations of cows fed the
      control diet were significantly lower compared with cows fed the contaminated
      diet. The calculated carryover rates ranged between 0 and 0.0075 for ZEN and
      metabolites and between 0 and 0.0017 for DON independent of exposure. It can be
      concluded that dietary toxin concentrations in the feed below or close to the
      current guidance values do not pose a risk for consumers due to negligible
      carryover rates.

PMID- 25849037
TI  - BTNL2 gene polymorphism and sarcoidosis susceptibility: a meta-analysis.
AB  - BACKGROUND: Butyrophilin-like 2 (BTNL2) rs2076530 gene polymorphism has been
      implicated in susceptibility to sarcoidosis. However, results from previous
      studies are not consistent. To assess the association of BTNL2 polymorphism and
      sarcoidosis susceptibility, a meta-analysis was performed. METHODS: PubMed,
      Embase were searched for eligible case-control studies. Data were extracted and
      pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated.
      RESULTS: Ten studies involving a total of 3303 cases and 2514 controls were
      included in this meta-analysis. Combined data indicated that BTNL2 rs2076530
      polymorphism was associated with sarcoidosis susceptibility in allelic model (A
      vs. G, OR = 1.59, 95%CI: 1.47-1.72), dominant model (AA + AG vs. GG, OR = 2.10,
      95%CI: 1.67-2.65), and recessive model (AA vs. AG + GG, OR = 1.93, 95%CI: 1.49
      2.50). CONCLUSIONS: This meta-analysis indicates that BTNL2 rs2076530
      polymorphism contributes to the risk of sarcoidosis.

PMID- 25849038
TI  - A novel pyrimidin-like plant activator stimulates plant disease resistance and
      promotes growth.
AB  - Plant activators are chemicals that induce plant defense responses to a broad
      spectrum of pathogens. Here, we identified a new potential plant activator, 5
      (cyclopropylmethyl)-6-methyl-2-(2-pyridyl)pyrimidin-4-ol, named PPA (pyrimidin
      type plant activator). Compared with benzothiadiazole S-methyl ester (BTH), a
      functional analog of salicylic acid (SA), PPA was fully soluble in water and
      increased fresh weight of rice (Oryza sativa) and Arabidopsis plants at low
      concentrations. In addition, PPA also promoted lateral root development.
      Microarray data and real-time PCR revealed that PPA-treated leaves not challenged
      with pathogen showed up-regulation of genes related to reactive oxygen species
      (ROS), defenses and SA. During bacterial infection, Arabidopsis plants pretreated
      with PPA showed dramatically decreased disease symptoms and an earlier and
      stronger ROS burst, compared with plants pretreated with BTH. Microscopy revealed
      that H2O2 accumulated in the cytosol, plasma membrane and cell wall around
      intracellular bacteria, and also on the bacterial cell wall, indicating that H2O2
      was directly involved in killing bacteria. The increase in ROS-related gene
      expression also supported this observation. Our results indicate that PPA
      enhances plant defenses against pathogen invasion through the plant redox system,
      and as a water-soluble compound that can promote plant growth, has broad
      potential applications in agriculture. 

PMID- 25849039
TI  - Effects of asymmetric nuclear introgression, introgressive mitochondrial sweep,
      and purifying selection on phylogenetic reconstruction and divergence estimates
      in the Pacific clade of Locustella warblers.
AB  - When isolated but reproductively compatible populations expand geographically and
      meet, simulations predict asymmetric introgression of neutral loci from a local
      to invading taxon. Genetic introgression may affect phylogenetic reconstruction
      by obscuring topology and divergence estimates. We combined phylogenetic analysis
      of sequences from one mtDNA and 12 nuDNA loci with analysis of gene flow among 5
      species of Pacific Locustella warblers to test for presence of genetic
      introgression and its effects on tree topology and divergence estimates. Our data
      showed that nuDNA introgression was substantial and asymmetrical among all
      members of superspecies groups whereas mtDNA showed no introgression except a
      single species pair where the invader's mtDNA was swept by mtDNA of the local
      species. This introgressive sweep of mtDNA had the opposite direction of the
      nuDNA introgression and resulted in the paraphyly of the local species' mtDNA
      haplotypes with respect to those of the invader. The multilocus nuDNA species
      tree resolved all inter- and intraspecific relationships despite substantial
      introgression. However, the node ages on the species tree may be underestimated
      as suggested by the differences in node age estimates based on non-introgressing
      mtDNA and introgressing nuDNA. In turn, the introgressive sweep and strong
      purifying selection appear to elongate internal branches in the mtDNA gene tree. 

PMID- 25849040
TI  - Mosquito-disseminated pyriproxyfen yields high breeding-site coverage and boosts
      juvenile mosquito mortality at the neighborhood scale.
AB  - BACKGROUND: Mosquito-borne pathogens pose major public health challenges
      worldwide. With vaccines or effective drugs still unavailable for most such
      pathogens, disease prevention heavily relies on vector control. To date, however,
      mosquito control has proven difficult, with low breeding-site coverage during
      control campaigns identified as a major drawback. A novel tactic exploits the egg
      laying behavior of mosquitoes to have them disseminate tiny particles of a potent
      larvicide, pyriproxyfen (PPF), from resting to breeding sites, thus improving
      coverage. This approach has yielded promising results at small spatial scales,
      but its wider applicability remains unclear. METHODOLOGY/PRINCIPAL FINDINGS: We
      conducted a four-month trial within a 20-month study to investigate mosquito
      driven dissemination of PPF dust-particles from 100 'dissemination stations'
      (DSs) deployed in a 7-ha sub-area to surveillance dwellings and sentinel breeding
      sites (SBSs) distributed over an urban neighborhood of about 50 ha. We assessed
      the impact of the trial by measuring juvenile mosquito mortality and adult
      mosquito emergence in each SBS-month. Using data from 1,075 dwelling-months,
      2,988 SBS-months, and 29,922 individual mosquitoes, we show that mosquito
      disseminated PPF yielded high coverage of dwellings (up to 100%) and SBSs (up to
      94.3%). Juvenile mosquito mortality in SBSs (about 4% at baseline) increased by
      over one order of magnitude during PPF dissemination (about 75%). This led to a
      >10-fold decrease of adult mosquito emergence from SBSs, from approximately 1,000
      3,000 adults/month before to about 100 adults/month during PPF dissemination.
      CONCLUSIONS/SIGNIFICANCE: By expanding breeding-site coverage and boosting
      juvenile mosquito mortality, a strategy based on mosquito-disseminated PPF has
      potential to substantially enhance mosquito control. Sharp declines in adult
      mosquito emergence can lower vector/host ratios, reducing the risk of disease
      outbreaks. This approach is a very promising complement to current and novel
      mosquito control strategies; it will probably be especially relevant for the
      control of urban disease vectors, such as Aedes and Culex species, that often
      cause large epidemics.

PMID- 25849042
TI  - Theoretical Investigation on the Reaction between OH Radical and 4,4-Dimethyl-1
      pentene in the Presence of O2.
AB  - The atmospheric oxidation mechanism of 4,4-dimethyl-1-pentene (DMP441) initiated
      by OH radical has been theoretically investigated at the BH&HLYP/6-311++G(d,p)
      and CCSD(T)/6-31+G(d,p) levels of theory. HC(O)H and 3,3-dimethylbutanal
      [(CH3)3CCH2C(O)H] are identified in our calculations as major products in the OH
      radical-initiated degradation of DMP441 in the presence of O2. However, the
      epoxide conformers and enols are expected to be minor products because of the
      high isomerization barriers involved. The calculated results are in qualitative
      accordance with experimental evidence. Conventional transition state theory has
      been used to calculate the rate constants of the initial addition channels of the
      OH + DMP441 reaction over the temperature range 220-500 K. The computed total
      rate constant at 298 K is 2.20 * 10(-11) cm(3) molecule(-1) s(-1), which is in
      very good agreement with the experimental value. Furthermore, it has been found
      that the calculated rate constant exhibits a weak non-Arrhenius behavior over the
      temperature range 220-500 K. The computed expression for the rate constant is
      k(OH+DMP441) = 1.22 * 10(-12) exp[(880 K)/T] cm(3) molecule(-1) s(-1). 

PMID- 25849041
TI  - Catecholamines promote Actinobacillus pleuropneumoniae growth by regulating iron
      metabolism.
AB  - Catecholamines are host stress hormones that can induce the growth of many
      bacteria by facilitating iron utilization and/or regulate the expression of
      virulence genes through specific hormone receptors. Whether these two responsive
      pathways are interconnected is unknown. In our previous study, it was found that
      catecholamines can regulate the expression of a great number of genes of
      Actinobacillus pleuropneumoniae, an important swine respiratory pathogen.
      However, bacterial growth was not affected by catecholamines in rich medium. In
      this study, it was discovered that catecholamines affected A. pleuropneumoniae
      growth in chemically defined medium (CDM). We found that serum inhibited A.
      pleuropneumoniae growth in CDM, while epinephrine, norepinephrine and dopamine
      promoted A. pleuropneumoniae growth in the CDM containing serum. The known
      bacterial hormone receptor QseC didn't play roles in this process. Ion
      supplementation and transcriptome analysis indicated that serum addition resulted
      in iron-restricted conditions which were alleviated by the addition of
      catecholamines. Transferrin, one of the components in serum, inhibited the growth
      of A. pleuropneumoniae in CDM, an effect reversed by addition of catecholamines
      in a TonB2-dependent manner. Our data demonstrate that catecholamines promote A.
      pleuropneumoniae growth by regulating iron-acquisition and metabolism, which is
      independent of the adrenergic receptor QseC. 

PMID- 25849043
TI  - Isostructural Re(I)/(99m)Tc(I) tricarbonyl complexes for cancer theranostics.
AB  - Merging classical organic anticancer drugs with metal-based compounds in one
      single molecule offers the possibility of exploring new approaches for cancer
      theranostics, i.e. the combination of diagnostic and therapeutic modalities. For
      this purpose, we have synthesized and biologically evaluated a series of
      Re(I)/(99m)Tc(I) tricarbonyl complexes (Re1-Re4 and Tc1-Tc4, respectively)
      stabilized by a cysteamine-based (N,S,O) chelator and containing 2-(4'
      aminophenyl)benzothiazole pharmacophores. With the exception of Re1, all the Re
      complexes have shown a moderate cytotoxicity in MCF7 and PC3 cancer cells (IC50
      values in the 15.9-32.1 MUM range after 72 h of incubation). The cytotoxic
      activity of the Re complexes is well correlated with cellular uptake that was
      quantified using the isostructural (99m)Tc congeners. There is an augmented
      cytotoxic effect for Re3 and Re4 (versusRe1 and Re2), and the highest cellular
      uptake for Tc3 and Tc4, which display a long ether-containing linker to couple
      the pharmacophore to the (N,S,O)-chelator framework. Moreover, fluorescence
      microscopy clearly confirmed the cytosolic accumulation of the most cytotoxic
      compound (Re3). Biodistribution studies of Tc1-Tc4 in mice confirmed that these
      moderately lipophilic complexes (logDo/w = 1.95-2.32) have a favorable
      bioavailability. Tc3 and Tc4 presented a faster excretion, as they undergo
      metabolic transformations, in contrast to complexes Tc1 and Tc2. In summary, our
      results show that benzothiazole-containing Re(I)/(99m)Tc(I) tricarbonyl complexes
      stabilized by cysteamine-based (N,S,O)-chelators have potential to be further
      applied in the design of new tools for cancer theranostics.

PMID- 25849044
TI  - Repeat work bouts increase thermal strain for Australian firefighters working in
      the heat.
AB  - BACKGROUND: Firefighters regularly re-enter fire scenes during long duration
      emergency events with limited rest between work bouts. It is unclear whether this
      practice is impacting on the safety of firefighters. OBJECTIVES: To evaluate the
      effects of multiple work bouts on firefighter physiology, strength, and cognitive
      performance when working in the heat. METHODS: Seventy-seven urban firefighters
      completed two 20-minute simulated search and rescue tasks in a heat chamber (105
      +/- 5 degrees C), separated by a 10-minute passive recovery. Core and skin
      temperature, rate of perceived exertion (RPE), thermal sensation (TS), grip
      strength, and cognitive changes between simulations were evaluated. RESULTS:
      Significant increases in core temperature and perceptual responses along with
      declines in strength were observed following the second simulation. No
      differences for other measures were observed. CONCLUSIONS: A significant increase
      in thermal strain was observed when firefighters re-entered a hot working
      environment. We recommend that longer recovery periods or active cooling methods
      be employed prior to re-entry.

PMID- 25849045
TI  - The solar magnetic activity band interaction and instabilities that shape quasi
      periodic variability.
AB  - Solar magnetism displays a host of variational timescales of which the enigmatic
      11-year sunspot cycle is most prominent. Recent work has demonstrated that the
      sunspot cycle can be explained in terms of the intra- and extra-hemispheric
      interaction between the overlapping activity bands of the 22-year magnetic
      polarity cycle. Those activity bands appear to be driven by the rotation of the
      Sun's deep interior. Here we deduce that activity band interaction can
      qualitatively explain the 'Gnevyshev Gap'-a well-established feature of flare and
      sunspot occurrence. Strong quasi-annual variability in the number of flares,
      coronal mass ejections, the radiative and particulate environment of the
      heliosphere is also observed. We infer that this secondary variability is driven
      by surges of magnetism from the activity bands. Understanding the formation,
      interaction and instability of these activity bands will considerably improve
      forecast capability in space weather and solar activity over a range of
      timescales.

PMID- 25849046
TI  - Connective tissue diseases: ICOS sustains pathogenic T-cell survival in SLE mouse
      model.

PMID- 25849047
TI  - Correction: genomic, proteomic, morphological, and phylogenetic analyses of
      vB_EcoP_SU10, a podoviridae phage with C3 morphology.

PMID- 25849049
TI  - Comparison of the effects of neuromuscular electrical stimulation and endurance
      training in patients with severe chronic obstructive pulmonary disease.
AB  - INTRODUCTION: In severely disabled patients who are not capable of following
      formal pulmonary rehabilitation (PR) and/or tolerating higher training
      intensities, neuromuscular electrical stimulation (NMES) has been successfully
      utilized as a localized training method. MATERIALS AND METHODS: In this non
      randomized controlled observational study 50 patients with severe chronic
      obstructive pulmonary disease (COPD), who were allocated into two groups.
      Endurance training group (ET) (n= 27) and NMES group (n= 23). To compare the
      effects of NMES and ET on health-related quality of life (HRQOL), exercise
      capacity, muscle strength, dyspnea, psychological status, and body composition in
      patients with severe COPD. Before and after PR program, the study parameters were
      assessed using the Medical Research Council (MRC) scale, incremental and
      endurance shuttle walking tests (ISWT, ESWT), manual muscle testing (MMT), the
      St. George's Respiratory Questionnaire (SGRQ), bioelectrical impedance analysis,
      and the Hospital Anxiety and Depression Scale (HADS). RESULTS: After the PR
      program, walking distance and endurance time significantly increased in both
      groups (p< 0.001 for each), whereas the MRC scores of both groups significantly
      decreased (p< 0.001 for each). In the ET group, significant decreases were noted
      in all domains of SGRQ and HADS. In the NMES group, significant improvements were
      observed in the HADS scores and in all SGRQ domain except symptom domain. No
      significant differences were observed between the NMES and ET groups regarding
      the changes from baseline to after PR program in walking distance (p= 0.140),
      endurance time (p= 0.376), the MRC (p= 0.540), HRQOL (p> 0.05) and HADS (p> 0.05)
      scores, body-mass index (BMI) (p= 0.49), fat-free mass (FFM) (p= 0.50) and fat
      free mass index (FFMI) (p= 0.94). CONCLUSION: NMES can be used as an effective
      treatment strategy in PR programs for peripheral muscle training in patients with
      severe COPD.

PMID- 25849050
TI  - Economic burden of nosocomial pneumonia in non-intensive care clinics.
AB  - INTRODUCTION: Almost all data on the cost of nosocomial pneumonia (NP) in the
      literature is associated with ventilator-associated pneumonia. This study aims to
      determine the economic burden of nosocomial pneumonia in clinical inpatients.
      MATERIALS AND METHODS: Data on costs of the 154 adult patients (97 male, 57
      female; mean age 64.53 +/- 14.92) who were hospitalized in non-intensive care
      clinics and developed NP were recorded prospectively. The control group consisted
      of 148 patients without pneumonia matched for age (mean age 65.66 +/- 13.86), sex
      (94 male), diagnosis, and hospitalization date. Data obtained from both groups of
      patients for the number of hospitalization days and the data obtained from the
      hospital automation program (Avicenna) for costs were compared using the Mann
      Whitney U test. RESULTS: While the mean duration of hospitalization was 32.8 days
      in patients with NP, it was 9.8 (p< 0.0001) in the control group. The cost of
      hospital beds was $631 for NP patients and $153 for the controls (p< 0.0001). The
      total cost was $6241 for NP patients and $1117 for the controls (p< 0.0001).
      CONCLUSION: NP is a high-cost condition that increases the duration of
      hospitalization 3.5-fold, hospital-bed cost 4-fold, and the total cost 5-fold.

PMID- 25849051
TI  - [Misdiagnosis of pulmonary embolism and causes].
AB  - INTRODUCTION: Pulmonary thromboembolism (PTE) is not only one of the prevelant
      diseases with a high mortality risk but also has a high ratio of delayed
      diagnosis and misdiagnosis. In this study, it was aimed to determine the
      demographical characteristics, risk factors, clinical and laboratory findings of
      the patients that were diagnosed as PTE at their first hospital visit and of the
      PE patients who were misdiagnosed at their first admission. We aimed to
      investigate the factors which can leads to misdiagnosis of PE, and to determine
      the ways to avoid misdiagnosis. MATERIALS AND METHODS: One hundred PTE patients
      who were admitted to University Hospital between the dates January 2007-December
      2011 were included in the study. Clinical and laboratory findings of these
      patients were evaluated. Among these patients, 26 were misdiagnosed at their
      first admission but diagnosed accurately (as PTE) in our hospital and 74 were
      diagnosed accurately. Two groups were compared with respect to various data of
      the patients clinical and demographical characteristics. RESULTS: Between the two
      groups, there was no difference in terms of physical examination and laboratory
      findings. The patients with the symptoms onset was over a week ago had a higher
      misdiagnosis rate (p= 0.002). The patients with no risk of PTE had a higher
      misdiagnosis rate (p= 0.017). Misdiagnosis rate of the patients with cardiac
      diseases was lower (p= 0.033) According to Geneva risk score, we observed that
      the misdiagnosis risk was reduced in the patients with higher clinical
      probability (p= 0.011). CONCLUSION: In conclusion, misdiagnosis rate was found to
      be statistically significant in the patients with low score according to the
      Geneva risk classification, and whose pre-diagnosis period lasted for more than a
      week and with no risk factors of PTE or cardiac diseases. We are in the opinion
      that considering these parameters will help to reduce in misdiagnosis of
      pulmonary embolism cases.

PMID- 25849048
TI  - Quantitative profiling of brain lipid raft proteome in a mouse model of fragile X
      syndrome.
AB  - Fragile X Syndrome, a leading cause of inherited intellectual disability and
      autism, arises from transcriptional silencing of the FMR1 gene encoding an RNA
      binding protein, Fragile X Mental Retardation Protein (FMRP). FMRP can regulate
      the expression of approximately 4% of brain transcripts through its role in
      regulation of mRNA transport, stability and translation, thus providing a
      molecular rationale for its potential pleiotropic effects on neuronal and brain
      circuitry function. Several intracellular signaling pathways are dysregulated in
      the absence of FMRP suggesting that cellular deficits may be broad and could
      result in homeostatic changes. Lipid rafts are specialized regions of the plasma
      membrane, enriched in cholesterol and glycosphingolipids, involved in regulation
      of intracellular signaling. Among transcripts targeted by FMRP, a subset encodes
      proteins involved in lipid biosynthesis and homeostasis, dysregulation of which
      could affect the integrity and function of lipid rafts. Using a quantitative mass
      spectrometry-based approach we analyzed the lipid raft proteome of Fmr1 knockout
      mice, an animal model of Fragile X syndrome, and identified candidate proteins
      that are differentially represented in Fmr1 knockout mice lipid rafts.
      Furthermore, network analysis of these candidate proteins reveals connectivity
      between them and predicts functional connectivity with genes encoding components
      of myelin sheath, axonal processes and growth cones. Our findings provide insight
      to aid identification of molecular and cellular dysfunctions arising from Fmr1
      silencing and for uncovering shared pathologies between Fragile X syndrome and
      other autism spectrum disorders. 

PMID- 25849052
TI  - The role of nailfold capillaroscopy in interstitial lung diseases - can it
      differentiate idiopathic cases from collagen tissue disease associated
      interstitial lung diseases?
AB  - INTRODUCTION: Nailfold capillaroscopy (NFC) is a non-invasive diagnostic test
      that is mostly used for early diagnosis of collagen tissue diseases (CTDs). We
      aimed to evaluate whether NFC findings could be a clue for discriminating
      idiopathic interstitial lung diseases (ILD) from CTD associated ILDs (CTD-ILD).
      Additionally it was aimed to determine whether NFC could be helpful in
      discriminating usual interstitial pneumonia (UIP) pattern from non-specific
      interstitial pneumonia (NSIP) pattern. MATERIALS AND METHODS: We grouped patients
      into three main groups: 15 CTD-ILD, 18 idiopathic ILD, and 17 patients in the
      control group. The CTD-ILD group was split into two subgroups: 8 patients with
      Sjogren's syndrome (SJS)-associated ILD and 7 with rheumatoid arthritis (RA)
      associated ILD. The idiopathic-ILD group consisted of 10 idiopathic NSIP and 8
      IPF patients. The control group consisted of 10 SJS and 7 RA patients without
      lung disease. None of the patients were on acute exacerbation at the time of
      examination, and none had Reynaud's phenomenon. RESULTS: Mean capillary density
      was significantly reduced only in the CTD-ILD group as compared to the control
      group (p= 0.006). In subgroup analysis, it was determined that RA-ILD, IPF, and
      SJS-ILD subgroups had more severe capillaroscopic abnormalities. Mean capillary
      density in patients with the UIP pattern was reduced compared to patients with
      the NSIP pattern and those in the control group; p values were 0.008 and < 0.001,
      respectively. CONCLUSION: This study is to be the first describing and comparing
      the nailfold capillaroscopic findings of patients with NSIP and UIP patterns. NFC
      findings can be helpful in discriminating UIP patterns from NSIP patterns. But to
      show its role in differentiating idiopathic disease, more studies with more
      patients are needed.

PMID- 25849053
TI  - A new approach in the diagnosis of upper airway resistance syndrome (UARS): PAP
      method.
AB  - INTRODUCTION: Upper airway resistance syndrome (UARS) is characterized by
      repeated number of arousals at night, and excessive daytime sleepiness or
      somnolence (EDS). It is often missed in classical polysomnographic diagnostic
      approaches and misdiagnosed as simple snoring or idiopathic hypersomnia, thereby
      is often left untreated. We propose that positive airway pressure (PAP), which
      has shown to be effective against UARS, can be used as a diagnostic tool as well.
      The study designed to test whether patients with high titration pressures can be
      diagnosed for UARS, and whether this pressure can be used as the treatment
      pressure in UARS. MATERIALS AND METHODS: This study is a retrospective cohort
      study. The patients with the following selection criteria: apnea hypopnea index
      (AHI) < 5, respiratory effort related arousal (RERA) index > 20, excessive
      daytime sleepiness or somnolence (EDS) without nocturnal oxygen desaturation
      levels were included to the study. After diagnostic polysomnography (PSG), PAP
      titrarion was applied to diagnose and treatment. RESULTS: Fourteen (%46.7) of the
      patients were male, 16 (%53.3) were female, with a mean age of 46.4 +/- 9.9 and
      mean body mass index (BMI) of 26 +/- 3.3. The patiens had a mean Epworth
      sleepiness scale 15.3 +/- 3.9, mean AHI: 2.3 +/- 1.4 and average RERA: 26.1 +/-
      4.9. The mean CPAP titration pressure was 7.1 +/- 1.1 cmH2O. CONCLUSION: In the
      light of current findings, during PAP titration patients required high pressures
      is the evidence of increased upper airway resistance in UARS. Using the from
      therapy to diagnosis protocol, the PAP protocol determines the individual
      therapeutic pressures needed by patients. Following up the clinical outcomes of
      these patients under the PAP treatment, and including a larger cohort will
      contribute greatly to treating this syndrome, defined as one of the "unresolved
      problems in years".

PMID- 25849054
TI  - A rarely seen diffuse parenchymal lung disease: diffuse pulmonary
      meningotheliomatosis.
AB  - Pulmonary meningothelial-like nodules (MLNs) are usually detected incidentally
      during pathologic evaluation of resected pulmonary parenchymal specimens and
      autopsies. These nodules are generally asymptomatic and most often single.
      Diffuse pulmonary involvement by MLNs is less frequently described. MLNs are
      benign lesions and have been associated with neoplastic and non-neoplastic
      pulmonary conditions and occasionally with extrapulmonary diseases. We report a
      case of a female patient presenting with multiple and bilateral pulmonary nodules
      diagnosed with "diffuse pulmonary meningotheliomatosis" by video-assisted
      thoracoscopic surgery (VATS). Diffuse pulmonary meningotheliomatosis should be
      included in the differential diagnosis of diffuse bilateral lung nodules in the
      radiologic studies. 

PMID- 25849055
TI  - [Sedation for fiberoptic bronchoscopy: review of the literature].
AB  - Fiberoptic bronchoscopy (FOB) is a procedure which has an important role in the
      diagnosis and treatment of lung diseases and is widely used in clinical practice.
      It is an invasive procedure and can cause cough, shortness of breath, nose and
      throat irritation. Stress during bronchoscopy can cause release of
      catecholamines, which may lead to tachycardia, vasoconstriction and possible
      myocardial ischemia in patients with impaired cardiopulmonary function. Current
      guidelines for bronchoscopy recommend offering sedation to patients, with the aim
      of improving patient comfort and reducing complications. For this purpose, the
      most frequently used sedatives are benzodiazepines, opioids, propofol and
      fospropofol which are either administered alone or in combination. In this
      review, we aimed to evaluate various drugs used for sedation during bronchoscopy.

PMID- 25849056
TI  - [A newly-defined entity: combined pulmonary fibrosis and emphysema syndrome].
AB  - Combined pulmonary fibrosis and emphysema (CPFE) syndrome is a rare disease
      characterized with shortness of breath, upper lobe emphysema, lower lobe fibrosis
      and impairment of gas exchange. This syndrome is a disease usually seen in male
      smokers. Pulmonary hypertension is associated with mortality. Another important
      feature, spirometric volumes relatively protected and a reduction in carbon
      monoxide diffusion test. CPFE syndrome in the literature so far have been
      identified in only 70 patients. In this review CPFE syndrome is presented with
      literature. 

PMID- 25849057
TI  - Perioperative evaluation for the patients with obstructive sleep apnea syndrome.
AB  - Obstructive sleep apnea syndrome, that has been more frequently diagnosed lately
      and whose importance has been gradually understood better, is a widespread health
      problem. This syndrome has been accompanied by obesity frequently. In the
      obstructive sleep apnea syndrome, it has been known that hypoxia and sometimes
      hypercarbia additionally has been observed, nevertheless cardiovascular problems
      have been observed more frequently in the aforementioned patient group in
      comparison with other individuals. Anesthetic substituents applied during the
      invasive operations and some medicine used for analgesia may cause the increase
      of the aforesaid hypoxia and cardiovascular problems in the obstructive sleep
      apnea syndrome. Nowadays, with the improvements in accessing to health agencies
      and consequently with the increase in the number of surgical applications, this
      review has been prepared with the thought of helping to clinicians about the
      approach and the pre-anesthetic and post-anesthetic precautions required to be
      taken within the mentioned patient group. 

PMID- 25849058
TI  - The value of endotracheal aspirate culture in newborn infants with ventilator
      associated pneumonia.

PMID- 25849059
TI  - A rare cause of bronchiectasis.

PMID- 25849060
TI  - Bochdalek hernia in a middle-aged man.

PMID- 25849061
TI  - A rare case of recurrent pneumonia: FMF.

PMID- 25849062
TI  - Images of Place: Visuals from Migrant Women Sex Workers in South Africa.
AB  - Many migrants in inner-city Johannesburg survive through unconventional and
      sometimes criminalized livelihood activities. In this article, we draw on data
      from a study that applied a participatory visual methodology to work with migrant
      women who sell sex, and explored the suitability of this approach as a way to
      engage with a presumed 'hard to reach' urban population. The lived experiences of
      migrant women sex workers were documented by combining participatory visual
      methods with a more traditional ethnographic approach, and this approach led us
      to new ways of seeing their worlds. This methodological approach raises important
      considerations for working with marginalized and criminalized urban groups. 

PMID- 25849063
TI  - Strategies for research recruitment and retention of older adults of racial and
      ethnic minorities.
AB  - HOW TO OBTAIN CONTACT HOURS BY READING THIS ARTICLE INSTRUCTIONS 1.4 contact
      hours will be awarded by Villanova University College of Nursing upon successful
      completion of this activity. A contact hour is a unit of measurement that denotes
      60 minutes of an organized learning activity. This is a learner-based activity.
      Villanova University College of Nursing does not require submission of your
      answers to the quiz. A contact hour certificate will be awarded once you
      register, pay the registration fee, and complete the evaluation form online at
      http://goo.gl/gMfXaf. To obtain contact hours you must: 1. Read the article,
      "Strategies for Research Recruitment and Retention of Older Adults of Racial and
      Ethnic Minorities" found on pages 14-23, carefully noting any tables and other
      illustrative materials that are included to enhance your knowledge and
      understanding of the content. Be sure to keep track of the amount of time (number
      of minutes) you spend reading the article and completing the quiz. 2. Read and
      answer each question on the quiz. After completing all of the questions, compare
      your answers to those provided within this issue. If you have incorrect answers,
      return to the article for further study. 3. Go to the Villanova website listed
      above to register for contact hour credit. You will be asked to provide your
      name; contact information; and a VISA, MasterCard, or Discover card number for
      payment of the $20.00 fee. Once you complete the online evaluation, a certificate
      will be automatically generated. This activity is valid for continuing education
      credit until April 30, 2018. CONTACT HOURS This activity is co-provided by
      Villanova University College of Nursing and SLACK Incorporated. Villanova
      University College of Nursing is accredited as a provider of continuing nursing
      education by the American Nurses Credentialing Center's Commission on
      Accreditation. ACTIVITY OBJECTIVE 1. Identify strategies and barriers for the
      recruitment and retention of older adults of racial and ethnic minorities in
      cognitive aging research. DISCLOSURE STATEMENT Neither the planners nor the
      authors have any conflicts of interest to disclose. The numbers of Hispanic and
      African American older adults in the United States are expected to increase by
      86% and more than 31%, respectively. African American and Hispanic American
      individuals are more likely than Caucasian individuals to have chronic health
      conditions, and researchers have argued that these health disparities may
      contribute to their higher rates of dementia-related illnesses. The current
      article explores strategies to improve participation in cognitive aging research
      by older adults, particularly minority older adults. The cultural aspects of
      cognitive aging are examined, especially the role of stigma and stereotype
      threat. The perceptions of cognitive aging of African American and Hispanic older
      adults are also described. Specific strategies are presented that have been
      successfully implemented to improve recruitment and retention in research
      targeting minority older adults. Strategies that yielded retention of minority
      older adults included advertising and marketing a randomized clinical trial,
      media relations, intervention tailoring, and adaptation of psychometric
      instruments.

PMID- 25849064
TI  - The Correlation of Social Support and Social Participation of Older Adults in
      Bandar Abbas, Iran.
AB  - Social participation is a criterion for successful aging. Research has shown that
      social participation decreases in older adults. However, the role of social
      support on older adults' social participation has received little attention,
      especially in eastern countries, such as Iran. Using the Social Participation
      Questionnaire, the relationship between social support and social participation
      was investigated in 525 Iranian older adults. A correlation was found between
      social support and social participation of older adults. Older adult women were
      found to have less social support and social participation compared with men.

PMID- 25849066
TI  - Efficient coupling of nanoparticles to electrochemically exfoliated graphene.
AB  - Electrochemically exfoliated graphene (EEG) is a new generation of high-quality
      graphene that holds great promise for the construction of hybrid materials.
      However, the assembly of EEG hybrids with well-defined nanostructures has
      remained a major challenge. In this study, we demonstrate a bottom-up approach
      toward the assembly of EEG sheets with a series of functional nanoparticles (Si,
      Fe3O4, and Pt NPs) into two-dimensional sandwich-like hybrid nanostructures.
      Polyaniline in the emeraldine base form functions as a versatile dopant to couple
      NPs onto EEG through either electrostatic interactions or hydrogen bonding. This
      protocol enables processing and assembly of EEG using an economical pathway, for
      which we further demonstrate the potential application of EEG-Si hybrids as high
      performance anode material for lithium storage. 

PMID- 25849065
TI  - Protective Effect of Super-Critical Carbon Dioxide Fluid Extract from Flowers and
      Buds of Chrysanthemum indicum Linnen Against Ultraviolet-Induced Photo-Aging in
      Mice.
AB  - It is known that solar ultraviolet (UV) radiation to human skin causes photo
      aging, including increases in skin thickness and wrinkle formation and reduction
      in skin elasticity. UV radiation induces damage to skin mainly by superfluous
      reactive oxygen species and chronic low-grade inflammation, which eventually up
      regulate the expression of matrix metalloproteinases (MMPs). In this study, the
      super-critical carbon dioxide extract from flowers and buds of Chrysanthemum
      indicum Linnen (CISCFE), which has been reported to possess free radical
      scavenging and anti-inflammatory properties, was investigated for its photo
      protective effect by topical application on the skin of mice. Moreover, CISCFE
      effectively suppressed the UV-induced increase in skin thickness and wrinkle
      grading in a dose-dependent manner, which was correlated with the inhibition of
      loss of collagen fiber content and epidermal thickening. Furthermore, we observed
      that CISCFE could obviously decrease UV-induced skin inflammation by inhibiting
      the production of inflammatory cytokines (interleukin-1beta [IL-1beta, IL-6, IL
      10, tumor necrosis factor-alpha), alleviate the abnormal changes of anti
      oxidative indicators (superoxide dismutase, catalase, and glutathione
      peroxidase), and down-regulate the levels of MMP-1 and MMP-3. The results
      indicated that CISCFE was a novel photo-protective agent from natural resources
      against UV irradiation. 

PMID- 25849067
TI  - NexGenEx-Tom: a gene expression platform to investigate the functionalities of
      the tomato genome.
AB  - BACKGROUND: Next Generation Sequencing technologies (NGS) unexpectedly pushed
      forward the capability of solving genome organization and of widely depicting
      gene expression. However, although the flourishing of tools to process the NGS
      data, versatile and user-friendly computational environments for integrative and
      comparative analyses of the results from the increasing amount of collections are
      still required. DESCRIPTION: Here we present the architecture and the facilities
      of NexGenEx-, a web based platform that offers processed NGS transcriptome
      collections and enables immediate analyses of the results. The platform allows
      gene expression investigations, profiling and comparisons, and exploits different
      resources. CONCLUSION: In the current version, NexGenEx-Tom includes processed
      and normalized NGS expression data from three collections covering several
      tissue/stages from different genotypes. Beyond providing a user-friendly
      interface, the platform was designed with the aim to easily be expanded to
      include other NGS based transcriptome collections. It can also integrate
      different genome releases, possibly from different cultivars or genotypes, but
      even from different species. The platform is proposed as an example effort in
      tomato, and is described as a profitable approach for the exploitation of these
      challenging and precious datasets.

PMID- 25849068
TI  - A Comparative Study Between the Wingate and Force-Velocity Anaerobic Cycling
      Tests: Effect of Physical Fitness.
AB  - PURPOSE: To verify the hypothesis that the peak power (PP) of a Wingate test (WT)
      is an underestimation of maximal power (P(max)) computed from the force-velocity
      test (FVT), to examine possible fatigue effect on P(max), and to investigate the
      effect of load on mean power (MP) and fatigue index (FI) during a WT in trained
      and recreational men. METHODS: Ten recreational (22.9 +/- 1.7 y, 1.81 +/- 0.06 m,
      73.3 +/- 10.4 kg) and 10 highly trained subjects (22.7 +/- 1.4 y, 1.85 +/- 0.05
      m, 78.9 +/- 6.6 kg) performed 2 WTs with 2 loads (8.7% and 11% of body mass [BM])
      and an FVT on the same cycle ergometer, in randomized order. RESULTS: Optimal
      load was equal to 10% BM in recreational participants. Given the quadratic
      relationship between load and power, the underestimation of P(max) was lower than
      10% for the average values of trained and recreational participants with both
      loads. However, PP with a load equal to 8.7% BM was a large underestimation
      (~30%) of P(max) in the most powerful individuals. In addition, PP was not
      greater than P(max) of FVT for the same load. FI was independent of the load only
      if it was expressed relative to PP. The optimal load for MP during WT was close
      to the optimal load for PP. CONCLUSIONS: The optimal load for WT performance
      should be approximately equal to 10% BM in recreational subjects. In powerful
      subjects, the FVT appears to be more appropriate in assessing maximal power, and
      loads higher than 11% BM should be verified for the WT.

PMID- 25849069
TI  - Cigarette smoke inhibits BAFF expression and mucosal immunoglobulin A responses
      in the lung during influenza virus infection.
AB  - BACKGROUND: It is incompletely understood how cigarette smoke (CS) exposure
      affects lung mucosal immune responses during viral respiratory infections. B cell
      activating factor belonging to the tumor necrosis factor family (BAFF) plays an
      important role in the induction of secretory immunoglobulin A (S-IgA) which is
      the main effector of the mucosal immune system. We therefore investigated the
      effects of CS exposure on BAFF expression and S-IgA responses in the lung during
      influenza virus infection. METHODS: Mice were exposed to CS and/or infected with
      influenza virus. Bronchoalveolar lavage fluid and lung compartments were analyzed
      for BAFF expression, influenza-specific S-IgA level and histological changes.
      Lung B cells were isolated and the activation-induced cytidine deaminase (Aicda)
      expression was determined. BEAS-2B cells were treated with CS extract (CSE),
      influenza virus, interferon beta or N-acetylcysteine and BAFF expression was
      measured. RESULTS: CS inhibited BAFF expression in the lung, particularly after
      long-term exposure. BAFF and S-IgA levels were increased during influenza virus
      infection. Three-month CS exposure prior to influenza virus infection resulted in
      reduced BAFF and S-IgA levels in the lung as well as augmented pulmonary
      inflammation on day 7 after infection. Prior CS exposure also caused decreased
      Aicda expression in lung B cells during infection. Neutralization of BAFF in the
      lung resulted in reduced S-IgA levels during influenza virus infection. CSE
      inhibited virus-mediated BAFF induction in a dose-dependent manner in BEAS-2B
      cells, while this inhibition of BAFF by CSE was prevented by pretreatment with
      the antioxidant N-acetylcysteine. CONCLUSIONS: Our findings indicate that CS may
      hinder early mucosal IgA responses in the lung during influenza virus infection
      through oxidative inhibition of BAFF, which might contribute to the increased
      incidence and severity of viral infections in smokers.

PMID- 25849070
TI  - Herbal medicines and chemotherapy induced peripheral neuropathy (CIPN): A
      critical literature review.
AB  - BACKGROUND: Chemotherapy induced peripheral neuropathy [CIPN] is a common
      significant and debilitating side-effect resulting from the administration of
      neurotoxic chemotherapeutic agents. These pharmaco-chemotherapeutics can include
      taxanes, vinca alkaloids, platinum analogues, and others. Moderate to severe CIPN
      significantly decreases the quality of life and physical abilities of cancer
      patients and current pharmacotherapy for CIPN e.g. Amifostine, and
      antidepressants have had limited efficacy and may themselves induce adverse side
      effects. METHODS: To determine the potential use of herbal medicines as adjuvants
      in cancer treatments, a critical literature review was conducted by electronic
      and manual search on nine databases. These include PubMed, the Cochrane Library,
      Science Direct, Scopus, EMBASE, MEDLINE, Google Scholar, and two Chinese
      databases CNKI and CINAHL. Thirty-four studies were selected from 5614 studies
      assessed and comprising animal studies, case reports, retrospective studies, and
      minimal randomized clinical trials investigating the anti-CIPN effect of herbal
      medicines as the adjuvant intervention in patients administered chemotherapy. The
      thirty-four studies were assessed on methodological quality and limitations
      identified. RESULTS: Studies were mixed in their recommendations for herbal
      medicines as an adjuvant treatment for CIPN. CONCLUSION: Currently no agent has
      shown solid beneficial evidence to be recommended for the treatment or
      prophylaxis of CIPN. Given that the number of cancer survivors is increasing, the
      long-term side effects of cancer treatment, is of major importance.

PMID- 25849071
TI  - Hidden voices: prevalence and risk factors for violence against women with
      disabilities in Nepal.
AB  - BACKGROUND: There is an increasing body of evidence on the extent and predictors
      of violence against women in Nepal. However, much of the published research does
      not yet take into account additional features of marginalization and
      vulnerability suffered by some women - for example, women socially excluded on
      account of their disability. Critical gaps exist in empirical data on the extent,
      risk factors, access to care, socio-economic and health consequences of violence
      among women with disabilities in Nepal. This paper addresses some these gaps and
      aims to promote evidence-informed policy and programme responses in Nepal.
      METHODS: We conducted a cross-sectional survey of 475 women with disability aged
      16 years and above in three districts in Nepal. In-depth interviews with 12 women
      who reported violence in the survey were also carried out. Using multivariate
      statistical methods we estimated the prevalence and risk factors for violence
      experienced both over the past 12 months and lifetime. RESULTS: Over the
      lifetime, 57.7% of women reported they had ever experienced violence, including
      emotional violence (55.2%); physical violence (34%); and sexual violence (21.5%).
      Over the preceding 12 months, 42% of women reported that they had experienced
      violence. Multivariate analysis showed that women with disabilities who were
      young, working in paid employment, and those who required permission from
      husbands/family to go to health centres or participate in community organizations
      were at increased risk of violence. Women experienced a range of negative
      outcomes from violence - including physical and emotional trauma. However, a
      majority of women did not seek care or redress from the health, justice or other
      sectors. CONCLUSIONS: Women in Nepal are at high risk of violence, often from
      members of their immediate family or local community. Rates of violence are
      higher in women with disability than among women in the general population.
      Tackling violence requires a comprehensive approach that addresses the root
      causes of women's unequal position in society, and builds upon principles of
      equity and justice to ensure that all women are able to realize their rights to a
      life free from violence.

PMID- 25849073
TI  - Structural features of Sm- and Gd-doped ceria studied by synchrotron X-ray
      diffraction and MU-Raman spectroscopy.
AB  - A structural study of Sm- and Gd-doped ceria was performed with the aim to
      clarify some unexplained structural features. (Ce1-xREx)O2-x/2 samples (RE = Sm,
      Gd; x = 0, 0.1, ..., 1) were prepared by coprecipitation of mixed oxalates and
      subsequent thermal treatment at 1473, 1173, or 1073 K in air; they were then
      analyzed at room temperature both by synchrotron X-ray diffraction and MU-Raman
      spectroscopy. Two structural models were adopted to fit the experimental data,
      namely, a fluoritic one, resembling the CeO2 structure at low RE content, and a
      hybrid one at higher RE content, intermediate between the CeO2 and the RE2O3
      structures. Two main transitions were detected along the compositional range: (a)
      an RE-dependent transition at the boundary between the fluoritic and the hybrid
      regions, of a chemical nature; (b) an RE-independent transition within the hybrid
      region at ~0.5, having a purely geometrical nature. The presence of two finely
      interlaced F- and C-based structures within the hybrid region was confirmed, and
      hints of their composition were obtained by MU-Raman spectroscopy. The obtained
      results indicate a possible explanation for the non-Vegard behavioral trend of
      the cell parameters. 

PMID- 25849072
TI  - Effective immuno-targeting of the IDH1 mutation R132H in a murine model of
      intracranial glioma.
AB  - The R132H mutation of cytosolic isocitrate dehydrogenase (IDH1) is present in the
      majority of low grade gliomas.Immunotherapy in these tumors has an interesting,
      still unexploited, therapeutic potential, as they are less immunosuppressive than
      glioblastomas. Using site-directed mutagenesis we introduced the R132H mutation
      into the murine glioma cell line GL261,creating mIDH1-GL261. Presence of the
      mutation was confirmed by immunoblotting and production of the oncometabolite 2
      hydroxyglutarate (2HG), demonstrated by mass spectrometry (LC-MS/MS) performed on
      cell supernatant. In vitro mIDH1-GL261 had different morphology but similar
      growth rate than parental GL261 (p-GL261). After intracranial injection, MRI
      suggested that the initial growth rate was slower in mIDH1-GL261 than p-GL261
      gliomas but overall survival was similar. mIDH1-GL261 gliomas showed evidence of
      R132H expression and of intratumoral 2HG production (evaluated by MRS and LC
      MS/MS). Immunizations were performed nine days after intracranial implantation of
      mIDH1- or p-GL261 cells by three subcutaneous injections of five different
      peptides encompassing the IDH1 mutation site, all emulsified with Montanide ISA
      51, in association with GM-CSF. Control mice were injected with four ovalbumin
      peptides or vehicle. Mice with mIDH1-GL261 but not p-GL261 gliomas treated with
      mIDH1 peptides survived longer than controls; 25% of them were cured. Immunized
      mice showed higher amounts of peripheral CD8+ T cells, higher production of IFN
      gamma, and evidence of anti-mIDH1 antibodies.Immunizations led to intratumoral up
      regulation of IFN-gamma, granzyme-b and perforin-1 and down-regulation of TGF
      beta2 and IL-10. These results support the translational potential of
      immunotherapeutic targeting of gliomas carrying IDH1 mutations.

PMID- 25849074
TI  - In vivo compatibility of graphene oxide with differing oxidation states.
AB  - Graphene oxide (GO) is suggested to have great potential as a component of
      biomedical devices. Although this nanomaterial has been demonstrated to be
      cytocompatible in vitro, its compatibility in vivo in tissue sites relevant for
      biomedical device application is yet to be fully understood. Here, we evaluate
      the compatibility of GO with two different oxidation levels following
      implantation in subcutaneous and intraperitoneal tissue sites, which are of broad
      relevance for application to medical devices. We demonstrate GO to be moderately
      compatible in vivo in both tissue sites, with the inflammatory reaction in
      response to implantation consistent with a typical foreign body reaction. A
      reduction in the degree of GO oxidation results in faster immune cell
      infiltration, uptake, and clearance following both subcutaneous and peritoneal
      implantation. Future work toward surface modification or coating strategies could
      be useful to reduce the inflammatory response and improve compatibility of GO as
      a component of medical devices. 

PMID- 25849075
TI  - Protein palmitoylation is critical for the polar growth of root hairs in
      Arabidopsis.
AB  - BACKGROUND: Protein palmitoylation, which is critical for membrane association
      and subcellular targeting of many signaling proteins, is catalyzed mainly by
      protein S-acyl transferases (PATs). Only a few plant proteins have been
      experimentally verified to be subject to palmitoylation, such as ROP GTPases,
      calcineurin B like proteins (CBLs), and subunits of heterotrimeric G proteins.
      However, emerging evidence from palmitoyl proteomics hinted that protein
      palmitoylation as a post-translational modification might be widespread.
      Nonetheless, due to the large number of genes encoding PATs and the lack of
      consensus motifs for palmitoylation, progress on the roles of protein
      palmitoylation in plants has been slow. RESULTS: We combined pharmacological and
      genetic approaches to examine the role of protein palmitoylation in root hair
      growth. Multiple PATs from different endomembrane compartments may participate in
      root hair growth, among which the Golgi-localized PAT24/TIP GROWTH DEFECTIVE1
      (TIP1) plays a major role while the tonoplast-localized PAT10 plays a secondary
      role in root hair growth. A specific inhibitor for protein palmitoylation, 2
      bromopalmitate (2-BP), compromised root hair elongation and polarity. Using
      various probes specific for cellular processes, we demonstrated that 2-BP
      impaired the dynamic polymerization of actin microfilaments (MF), the asymmetric
      plasma membrane (PM) localization of phosphatidylinositol (4,5)-bisphosphate
      (PIP2), the dynamic distribution of RabA4b-positive post-Golgi secretion, and
      endocytic trafficking in root hairs. CONCLUSIONS: By combining pharmacological
      and genetic approaches and using root hairs as a model, we show that protein
      palmitoylation, regulated by protein S-acyl transferases at different
      endomembrane compartments such as the Golgi and the vacuole, is critical for the
      polar growth of root hairs in Arabidopsis. Inhibition of protein palmitoylation
      by 2-BP disturbed key intracellular activities in root hairs. Although some of
      these effects are likely indirect, the cytological data reported here will
      contribute to a deep understanding of protein palmitoylation during tip growth in
      plants.

PMID- 25849076
TI  - A nontoxic polypeptide oligomer with a fungicide potency under agricultural
      conditions which is equal or greater than that of their chemical counterparts.
AB  - There are literally hundreds of polypeptides described in the literature which
      exhibit fungicide activity. Tens of them have had attempted protection by patent
      applications but none, as far as we are aware, have found application under real
      agricultural conditions. The reasons behind may be multiple where the sensitivity
      to the Sun UV radiation can come in first place. Here we describe a
      multifunctional glyco-oligomer with 210 kDa which is mainly composed by a 20 kDa
      polypeptide termed Blad that has been previously shown to be a stable
      intermediary product of beta-conglutin catabolism. This oligomer accumulates
      exclusively in the cotyledons of Lupinus species, between days 4 and 12 after the
      onset of germination. Blad-oligomer reveals a plethora of biochemical properties,
      like lectin and catalytic activities, which are not unusual per si, but are
      remarkable when found to coexist in the same protein molecule. With this vast
      range of chemical characteristics, antifungal activity arises almost as a natural
      consequence. The biological significance and potential technological applications
      of Blad-oligomer as a plant fungicide to agriculture, its uniqueness stems from
      being of polypeptidic in nature, and with efficacies which are either equal or
      greater than the top fungicides currently in the market are addressed. 

PMID- 25849077
TI  - Control of rhGH Release Profile from PEG-PAF Thermogel.
AB  - Poly(ethylene glycol)-poly(l-alanine-co-l-phenyl alanine) diblock copolymers (PEG
      PAF) of 2000-990 Da (P2K) and 5000-2530 Da (P5K) with the different molecular
      weights of PEGs, but having a similar molecular weight ratio of hydrophobic block
      to hydrophilic block were synthesized to compare their solution behavior and
      corresponding protein drug release profiles from their in situ formed thermogels.
      The PEG-PAF aqueous solutions underwent heat-induced sol-to-gel transition in a
      concentration range of 18.0-24.0 wt % and 8.0-12.0 wt % for P2K and P5K,
      respectively. P5K formed bigger micelles than P2K, of a broad distribution,
      whereas the PAF blocks of P5K developed richer in alpha-helix than those of P2K
      in the core of the micelles. As the temperature increased, the micelles underwent
      dehydration of the PEG, which led to the aggregation of micelles, while the
      secondary structure of PAF was slightly affected during the sol-to-gel
      transition. The P5K exhibited higher tendency to aggregate and formed a tighter
      gel than P2K. Upon injection into the subcutaneous layer of rats, both polymer
      aqueous solutions formed a biocompatible gel with typical mild inflammatory
      tissue responses. Recombinant human growth hormone (rhGH) maintained its
      stability without forming any aggregates in both sol (4  degrees C) and gel (37 
      degrees C) states of the PEG-PAFs. Even though P2K and P5K have a similar
      molecular weight ratio of hydrophobic block to hydrophilic block, the P5K system
      exhibited a reduced initial burst release, improved bioavailability, and
      prolonged therapeutic duration of the rhGH, compared to the P2K system. The
      current research suggests that a drug release profile is a complex function of
      self-assembling carriers and incorporated drugs, and thus, a promising protein
      delivery system could be designed by adjusting the molecular parameters of a
      thermogel. 

PMID- 25849078
TI  - RNA-mediated degradation of microRNAs: A widespread viral strategy?
AB  - Regulation of small RNAs by other non-coding RNAs is a ubiquitous feature of gene
      regulatory systems that can be exploited by viruses. Examples of this have been
      described in 3 different herpesviruses, where viral non-coding RNAs bind to
      highly abundant cellular (miRNAs), mediating their degradation: miR-27 is
      targeted by both murine cytomegalovirus and herpesvirus saimiri, while the miR-17
      family is targeted by human cytomegalovirus. We review what is known about RNA
      mediated regulation of miRNA stability and propose 3 potential roles that viral
      non-coding RNAs might assume to initiate the destruction of a miRNA, acting as
      "recruiters," "localizers" or "exposers." Whereas the miRNAs (miR-17 and miR-27)
      appear to be ancient and pre-date the common ancestor of all mammalian
      herpesviruses, comparative analyses of herpesvirus genomes indicate that the 3
      known viral regulators of miRNA each evolved independently, and much more
      recently. Noting that the anti-viral activity of miRNAs might be countered by a
      variety of mechanisms, we propose that (i) there has been continual turnover of
      these mechanisms during herpesvirus evolution, and (ii) there may be many other,
      as yet undescribed, anti-miRNA activities encoded by other herpesviruses and
      indeed by viruses from other families. 

PMID- 25849079
TI  - The transcriptome signature of the receptive bovine uterus determined at early
      gestation.
AB  - Pregnancy success is critical to the profitability of cattle operations. However,
      the molecular events driving the uterine tissue towards embryo receptivity are
      poorly understood. This study aimed to characterize the uterine transcriptome
      profiles of pregnant (P) versus non-pregnant (NP) cows during early pregnancy and
      attempted to define a potential set of marker genes that can be valuable for
      predicting pregnancy outcome. Therefore, beef cows were synchronized (n=51) and
      artificially inseminated (n=36) at detected estrus. Six days after AI (D6),
      jugular blood samples and a biopsy from the uterine horn contralateral to the
      ovary containing the corpus luteum were collected. Based on pregnancy outcome on
      D30, samples were retrospectively allocated to the following groups: P (n=6) and
      NP (n=5). Both groups had similar plasma progesterone concentrations on D6.
      Uterine biopsies were submitted to RNA-Seq analysis in a Illumina platform. The
      272,685,768 million filtered reads were mapped to the Bos Taurus reference genome
      and 14,654 genes were analyzed for differential expression between groups.
      Transcriptome data showed that 216 genes are differently expressed when comparing
      NP versus P uterine tissue (Padj <= 0.1). More specifically, 36 genes were up
      regulated in P cows and 180 are up-regulated in NP cows. Functional enrichment
      and pathway analyses revealed enriched expression of genes associated with
      extracellular matrix remodeling in the NP cows and nucleotide binding, microsome
      and vesicular fraction in the P cows. From the 40 top-ranked genes, the
      transcript levels of nine genes were re-evaluated using qRT-PCR. In conclusion,
      this study characterized a unique set of genes, expressed in the uterus 6 days
      after insemination, that indicate a receptive state leading to pregnancy success.
      Furthermore, expression of such genes can be used as potential markers to
      efficiently predict pregnancy success.

PMID- 25849080
TI  - Unique honey bee (Apis mellifera) hive component-based communities as detected by
      a hybrid of phospholipid fatty-acid and fatty-acid methyl ester analyses.
AB  - Microbial communities (microbiomes) are associated with almost all metazoans,
      including the honey bee Apis mellifera. Honey bees are social insects,
      maintaining complex hive systems composed of a variety of integral components
      including bees, comb, propolis, honey, and stored pollen. Given that the
      different components within hives can be physically separated and are
      nutritionally variable, we hypothesize that unique microbial communities may
      occur within the different microenvironments of honey bee colonies. To explore
      this hypothesis and to provide further insights into the microbiome of honey
      bees, we use a hybrid of fatty acid methyl ester (FAME) and phospholipid-derived
      fatty acid (PLFA) analysis to produce broad, lipid-based microbial community
      profiles of stored pollen, adults, pupae, honey, empty comb, and propolis for 11
      honey bee hives. Averaging component lipid profiles by hive, we show that, in
      decreasing order, lipid markers representing fungi, Gram-negative bacteria, and
      Gram-positive bacteria have the highest relative abundances within honey bee
      colonies. Our lipid profiles reveal the presence of viable microbial communities
      in each of the six hive components sampled, with overall microbial community
      richness varying from lowest to highest in honey, comb, pupae, pollen, adults and
      propolis, respectively. Finally, microbial community lipid profiles were more
      similar when compared by component than by hive, location, or sampling year.
      Specifically, we found that individual hive components typically exhibited
      several dominant lipids and that these dominant lipids differ between components.
      Principal component and two-way clustering analyses both support significant
      grouping of lipids by hive component. Our findings indicate that in addition to
      the microbial communities present in individual workers, honey bee hives have
      resident microbial communities associated with different colony components. 

PMID- 25849081
TI  - Reduced Tyk2 gene expression in beta-cells due to natural mutation determines
      susceptibility to virus-induced diabetes.
AB  - Accumulating evidence suggests that viruses play an important role in the
      development of diabetes. Although the diabetogenic encephalomyocarditis strain D
      virus induces diabetes in restricted lines of inbred mice, the susceptibility
      genes to virus-induced diabetes have not been identified. We report here that
      novel Tyrosine kinase 2 (Tyk2) gene mutations are present in virus-induced
      diabetes-sensitive SJL and SWR mice. Mice carrying the mutant Tyk2 gene on the
      virus-resistant C57BL/6 background are highly sensitive to virus-induced
      diabetes. Tyk2 gene expression is strongly reduced in Tyk2-mutant mice,
      associated with low Tyk2 promoter activity, and leads to decreased expression of
      interferon-inducible genes, resulting in significantly compromised antiviral
      response. Tyk2-mutant pancreatic beta-cells are unresponsive even to high dose of
      Type I interferon. Reversal of virus-induced diabetes could be achieved by beta
      cell-specific Tyk2 gene expression. Thus, reduced Tyk2 gene expression in
      pancreatic beta-cells due to natural mutation is responsible for susceptibility
      to virus-induced diabetes. 

PMID- 25849082
TI  - Genetic mapping of QTLs controlling fatty acids provided insights into the
      genetic control of fatty acid synthesis pathway in peanut (Arachis hypogaea L.).
AB  - Peanut, a high-oil crop with about 50% oil content, is either crushed for oil or
      used as edible products. Fatty acid composition determines the oil quality which
      has high relevance to consumer health, flavor, and shelf life of commercial
      products. In addition to the major fatty acids, oleic acid (C18:1) and linoleic
      acid (C18:2) accounting for about 80% of peanut oil, the six other fatty acids
      namely palmitic acid (C16:0), stearic acid (C18:0), arachidic acid (C20:0),
      gadoleic acid (C20:1), behenic acid (C22:0), and lignoceric acid (C24:0) are
      accounted for the rest 20%. To determine the genetic basis and to improve further
      understanding on effect of FAD2 genes on these fatty acids, two recombinant
      inbred line (RIL) populations namely S-population (high oleic line 'SunOleic 97R'
      * low oleic line 'NC94022') and T-population (normal oleic line 'Tifrunner' * low
      oleic line 'GT-C20') were developed. Genetic maps with 206 and 378 marker loci
      for the S- and the T-population, respectively were used for quantitative trait
      locus (QTL) analysis. As a result, a total of 164 main-effect (M-QTLs) and 27
      epistatic (E-QTLs) QTLs associated with the minor fatty acids were identified
      with 0.16% to 40.56% phenotypic variation explained (PVE). Thirty four major QTLs
      (>10% of PVE) mapped on five linkage groups and 28 clusters containing more than
      three QTLs were also identified. These results suggest that the major QTLs with
      large additive effects would play an important role in controlling composition of
      these minor fatty acids in addition to the oleic and linoleic acids in peanut
      oil. The interrelationship among these fatty acids should be considered while
      breeding for improved peanut genotypes with good oil quality and desired fatty
      acid composition. 

PMID- 25849084
TI  - Surface tension of supercooled water determined by using a counterpressure
      capillary rise method.
AB  - Measurements of the surface tension of supercooled water down to -25  degrees C
      have been reported recently (Hruby et al. J. Phys. Chem. Lett. 2014, 5, 425-428).
      These experiments did not show any anomalous temperature dependence of the
      surface tension of supercooled water reported by some earlier measurements and
      molecular simulations. In the present work, this finding is confirmed using a
      counterpressure capillary rise method (the counterpressure method) as well as
      through the use of the classical capillary rise method (the height method). In
      the counterpressure method, the liquid meniscus inside the vertical capillary
      tube was kept at a fixed position with an in-house developed helium distribution
      setup. A preset counterpressure was applied to the liquid meniscus when its
      temperature changed from a reference temperature (30  degrees C) to the
      temperature of interest. The magnitude of the counterpressure was adjusted such
      that the meniscus remained at the same height, thus compensating the change of
      the surface tension. One advantage of the counterpressure method over the height
      method consists of avoiding the uncertainty due to a possible variation of the
      capillary diameter along its length. A second advantage is that the equilibration
      time due to the capillary flow of the highly viscous supercooled water can be
      shortened. For both the counterpressure method and the height method, the actual
      results are relative values of surface tension with respect to the surface
      tension of water at the reference temperature. The combined relative standard
      uncertainty of the relative surface tensions is less than or equal to 0.18%. The
      new data between -26 and +30  degrees C lie close to the IAPWS correlation for
      the surface tension of ordinary water extrapolated below 0.01  degrees C and do
      not exhibit any anomalous features. 

PMID- 25849083
TI  - Delineating species with DNA barcodes: a case of taxon dependent method
      performance in moths.
AB  - The accelerating loss of biodiversity has created a need for more effective ways
      to discover species. Novel algorithmic approaches for analyzing sequence data
      combined with rapidly expanding DNA barcode libraries provide a potential
      solution. While several analytical methods are available for the delineation of
      operational taxonomic units (OTUs), few studies have compared their performance.
      This study compares the performance of one morphology-based and four DNA-based
      (BIN, parsimony networks, ABGD, GMYC) methods on two groups of gelechioid moths.
      It examines 92 species of Finnish Gelechiinae and 103 species of Australian
      Elachistinae which were delineated by traditional taxonomy. The results reveal a
      striking difference in performance between the two taxa with all four DNA-based
      methods. OTU counts in the Elachistinae showed a wider range and a relatively low
      (ca. 65%) OTU match with reference species while OTU counts were more congruent
      and performance was higher (ca. 90%) in the Gelechiinae. Performance rose when
      only monophyletic species were compared, but the taxon-dependence remained. None
      of the DNA-based methods produced a correct match with non-monophyletic species,
      but singletons were handled well. A simulated test of morphospecies-grouping
      performed very poorly in revealing taxon diversity in these small, dull-colored
      moths. Despite the strong performance of analyses based on DNA barcodes, species
      delineated using single-locus mtDNA data are best viewed as OTUs that require
      validation by subsequent integrative taxonomic work. 

PMID- 25849085
TI  - Spectroscopic Characterization of Structural Changes in Membrane Scaffold
      Proteins Entrapped within Mesoporous Silica Gel Monoliths.
AB  - The changes in the orientation and conformation of three different membrane
      scaffold proteins (MSPs) upon entrapment in sol-gel-derived mesoporous silica
      monoliths were investigated. MSPs were examined in either a lipid-free or a lipid
      bound conformation, where the proteins were associated with lipids to form
      nanolipoprotein particles (NLPs). NLPs are water-soluble, disk-shaped patches of
      a lipid bilayer that have amphiphilic MSPs shielding the hydrophobic lipid tails.
      The NLPs in this work had an average thickness of 5 nm and diameters of 9.2, 9.7,
      and 14.8 nm. We have previously demonstrated that NLPs are more suitable lipid
      based structures for silica gel entrapment than liposomes because of their size
      compatibility with the mesoporous network (2-50 nm) and minimally altered
      structure after encapsulation. Here we further elaborate on that work by using a
      variety of spectroscopic techniques to elucidate whether or not different MSPs
      maintain their protein-lipid interactions after encapsulation. Fluorescence
      spectroscopy and quenching of the tryptophan residues with acrylamide, 5-DOXYL
      stearic acid, and 16-DOXYL-stearic acid were used to determine the MSP
      orientation. We also utilized fluorescence anisotropy of tryptophans to measure
      the relative size of the NLPs and MSP aggregates after entrapment. Finally,
      circular dichroism spectroscopy was used to examine the secondary structure of
      the MSPs. Our results showed that, after entrapment, all of the lipid-bound MSPs
      maintained orientations that were minimally changed and indicative of association
      with lipids in NLPs. The tryptophan residues appeared to remain buried within the
      hydrophobic core of the lipid tails in the NLPs and appropriately spaced from the
      bilayer center. Also, after entrapment, lipid-bound MSPs maintained a high degree
      of alpha-helical content, a secondary structure associated with protein-lipid
      interactions. These findings demonstrate that NLPs are capable of serving as
      viable hosts for functional integral membrane proteins in the synthesis of sol
      gel-derived bioinorganic hybrid nanomaterials. 

PMID- 25849087
TI  - Do hotter temperatures increase the incidence of self-harm hospitalisations?
AB  - A relationship between air temperature and the incidence of suicide has been
      established in a number of previous studies. Interestingly, the relationship
      between geographical variation in temperature and suicide incidence has generally
      been found to be negative, while the relationship between temporal variation in
      temperature and suicide incidence has generally been found to be positive. It is
      less clear, however, how temperature relates to the incidence of self-harm. This
      topic is of particular importance given the presence of ongoing global warming.
      This study investigated the relationship between temperature and the incidence of
      self-harm resulting in hospitalisation in New Zealand. Self-harm hospitalisations
      by date and district for 1993-2009 were obtained from the Ministry of Health.
      Meteorological data was obtained from NIWA. Generalised linear mixed models were
      used to estimate the effects of three different components of variation in
      temperature: geographical, seasonal and irregular. Irregular (random) daily
      variation in temperature had a modest positive relationship with the incidence of
      acts of self-harm resulting in hospitalisation, with about 0.7% extra incidents
      for every 1  degrees C increase in temperature. However, there was no strong
      evidence for a positive effect of either seasonal or geographical variation in
      temperature. We conclude that temperature does appear to bear some relation to
      the incidence of self-harm, with irregular daily variation in temperature having
      a positive effect. However, inconsistencies in the effects of different
      components of variation in temperature make it challenging to accurately predict
      how global warming will influence the incidence of self-harm.

PMID- 25849086
TI  - Use of nuclear magnetic resonance-based metabolomics to characterize the
      biochemical effects of naphthalene on various organs of tolerant mice.
AB  - Naphthalene, the most common polycyclic aromatic hydrocarbon, causes airway
      epithelium injury in mice. Repeated exposure of mice to naphthalene induces
      airway epithelia that are resistant to further injury. Previous studies revealed
      that alterations in bioactivation enzymes and increased levels of gamma
      glutamylcysteine synthase in the bronchioles protect tolerant mice from
      naphthalene and its reactive metabolites. In our current study, tolerance was
      induced in male ICR mice using a total of 7 daily intraperitoneal injections of
      naphthalene (200 mg/kg). Both naphthalene-tolerant and non-tolerant mice were
      challenged with a dose of 300 mg/kg naphthalene on day 8 to investigate
      metabolite differences. The lungs, liver, and kidneys were collected for
      histopathology 24 h after the challenge dose. Bronchial alveolar lavage fluid
      (BALF) and both hydrophilic and hydrophobic extracts from each organ were
      analyzed using nuclear magnetic resonance (NMR)-based metabolomics. The
      histological results showed no observable injuries to the airway epithelium of
      naphthalene-tolerant mice when compared with the control. In contrast, airway
      injuries were observed in mice given a single challenge dose (injury mice). The
      metabolomics analysis revealed that the energy metabolism in the lungs of
      tolerant and injury mice was significantly perturbed. However, antioxidant
      metabolites, such as glutathione and succinate, were significantly increased in
      the lungs of tolerant mice, suggesting a role for these compounds in the
      protection of organs from naphthalene-induced electrophilic metabolites and free
      radicals. Damage to the airway cellular membrane, as shown by histopathological
      results and increased acetone in the BALF and perturbation of hydrophobic lung
      extracts, including cholesterol, phosphorylcholine-containing lipids, and fatty
      acyl chains, were observed in injury mice. Consistent with our histopathological
      results, fewer metabolic effects were observed in the liver and kidney of mice
      after naphthalene treatments. In conclusion, NMR-based metabolomics reveals
      possible mechanisms of naphthalene tolerance and naphthalene-induced toxicity in
      the respiratory system of mice. 

PMID- 25849088
TI  - Bubble-induced cave collapse.
AB  - Conventional wisdom among cave divers is that submerged caves in aquifers, such
      as in Florida or the Yucatan, are unstable due to their ever-growing size from
      limestone dissolution in water. Cave divers occasionally noted partial cave
      collapses occurring while they were in the cave, attributing this to their
      unintentional (and frowned upon) physical contact with the cave walls or the
      aforementioned "natural" instability of the cave. Here, we suggest that these
      cave collapses do not necessarily result from cave instability or contacts with
      walls, but rather from divers bubbles rising to the ceiling and reducing the
      buoyancy acting on isolated ceiling rocks. Using familiar theories for the
      strength of flat and arched (un-cracked) beams, we first show that the flat
      ceiling of a submerged limestone cave can have a horizontal expanse of 63 meters.
      This is much broader than that of most submerged Florida caves (~ 10 m).
      Similarly, we show that an arched cave roof can have a still larger expanse of
      240 meters, again implying that Florida caves are structurally stable. Using
      familiar bubble dynamics, fluid dynamics of bubble-induced flows, and accustomed
      diving practices, we show that a group of 1-3 divers submerged below a loosely
      connected ceiling rock will quickly trigger it to fall causing a "collapse". We
      then present a set of qualitative laboratory experiments illustrating such a
      collapse in a circular laboratory cave (i.e., a cave with a circular cross
      section), with concave and convex ceilings. In these experiments, a metal ball
      represented the rock (attached to the cave ceiling with a magnet), and the
      bubbles were produced using a syringe located at the cave floor. 

PMID- 25849090
TI  - The correlation between running economy and maximal oxygen uptake: cross
      sectional and longitudinal relationships in highly trained distance runners.
AB  - A positive relationship between running economy and maximal oxygen uptake
      (VO2max) has been postulated in trained athletes, but previous evidence is
      equivocal and could have been confounded by statistical artefacts. Whether this
      relationship is preserved in response to running training (changes in running
      economy and VO2max) has yet to be explored. This study examined the relationships
      of (i) running economy and VO2max between runners, and (ii) the changes in
      running economy and VO2max that occur within runners in response to habitual
      training. 168 trained distance runners (males, n = 98, VO2max 73.0 +/- 6.3 mL?kg
      1?min-1; females, n = 70, VO2max 65.2 +/- 5.9 mL kg-1?min-1) performed a
      discontinuous submaximal running test to determine running economy (kcal?km-1). A
      continuous incremental treadmill running test to volitional exhaustion was used
      to determine VO2max 54 participants (males, n = 27; females, n = 27) also
      completed at least one follow up assessment. Partial correlation analysis
      revealed small positive relationships between running economy and VO2max (males r
      = 0.26, females r = 0.25; P<0.006), in addition to moderate positive
      relationships between the changes in running economy and VO2max in response to
      habitual training (r = 0.35; P<0.001). In conclusion, the current investigation
      demonstrates that only a small to moderate relationship exists between running
      economy and VO2max in highly trained distance runners. With >85% of the variance
      in these parameters unexplained by this relationship, these findings reaffirm
      that running economy and VO2max are primarily determined independently. 

PMID- 25849091
TI  - Effects of Temperature, Humidity and Air Flow on Fungal Growth Rate on Loaded
      Ventilation Filters.
AB  - This study compares the fungal growth ratio on loaded ventilation filters under
      various temperature, relative humidity (RH), and air flow conditions in a
      controlled laboratory setting. A new full-size commercial building ventilation
      filter was loaded with malt extract nutrients and conidia of Cladosporium
      sphaerospermum in an ASHRAE Standard 52.2 filter test facility. Small sections
      cut from this filter were incubated under the following conditions: constant room
      temperature and a high RH of 97%; sinusoidal temperature (with an amplitude of 10
      degrees C, an average of 23 degrees C, and a period of 24 hr) and a mean RH of
      97%; room temperature and step changes between 97% and 75% RH, 97% and 43% RH,
      and 97% and 11% RH every 12 hr. The biomass on the filter sections was measured
      using both an elution-culture method and by ergosterol assay immediately after
      loading and every 2 days up to 10 days after loading. Fungal growth was detected
      earlier using ergosterol content than with the elution-culture method. A
      student's t-test indicated that Cladosporium sphaerospermum grew better at the
      constant room temperature condition than at the sinusoidal temperature condition.
      By part-time exposure to dry environments, the fungal growth was reduced (75% and
      43% RH) or even inhibited (11% RH). Additional loaded filters were installed in
      the wind tunnel at room temperature and an RH greater than 95% under one of two
      air flow test conditions: continuous air flow or air flow only 9 hr/day with a
      flow rate of 0.7 m(3)/s (filter media velocity 0.15 m/s). Swab tests and a tease
      mount method were used to detect fungal growth on the filters at day 0, 5, and
      10. Fungal growth was detected for both test conditions, which indicates that
      when temperature and relative humidity are optimum, controlling the air flow
      alone cannot prevent fungal growth. In real applications where nutrients are less
      sufficient than in this laboratory study, fungal growth rate may be reduced under
      the same operating conditions.

PMID- 25849089
TI  - Association of small dense LDL serum levels and circulating monocyte subsets in
      stable coronary artery disease.
AB  - OBJECTIVE: Atherosclerosis is considered to be an inflammatory disease in which
      monocytes and monocyte-derived macrophages play a key role. Circulating monocytes
      can be divided into three distinct subtypes, namely in classical monocytes (CM;
      CD14++CD16-), intermediate monocytes (IM; CD14++CD16+) and non-classical
      monocytes (NCM; CD14+CD16++). Low density lipoprotein particles are heterogeneous
      in size and density, with small, dense LDL (sdLDL) crucially implicated in
      atherogenesis. The aim of this study was to examine whether monocyte subsets are
      associated with sdLDL serum levels. METHODS: We included 90 patients with
      angiographically documented stable coronary artery disease and determined
      monocyte subtypes by flow cytometry. sdLDL was measured by an electrophoresis
      method on polyacrylamide gel. RESULTS: Patients with sdLDL levels in the highest
      tertile (sdLDL>=4mg/dL;T3) showed the highest levels of pro-inflammatory NCM
      (15.2+/-7% vs. 11.4+/-6% and 10.9+/-4%, respectively; p<0.01) when compared with
      patients in the middle (sdLDL=2-3mg/dL;T2) and lowest tertile (sdLDL=0
      1mg/dL;T1). Furthermore, patients in the highest sdLDL tertile showed lower CM
      levels than patients in the middle and lowest tertile (79.2+/-8% vs. 83.9+/-7%
      and 82.7+/-5%; p<0.01 for T3 vs. T2+T1). Levels of IM were not related to sdLDL
      levels (5.6+/-4% vs. 4.6+/-3% vs. 6.4+/-3% for T3, T2 and T1, respectively). In
      contrast to monocyte subset distribution, levels of circulating pro- and anti
      inflammatory markers were not associated with sdLDL levels. CONCLUSION: The
      atherogenic lipoprotein fraction sdLDL is associated with an increase of NCM and
      a decrease of CM. This could be a new link between lipid metabolism
      dysregulation, innate immunity and atherosclerosis.

PMID- 25849092
TI  - The therapeutic effects of docosahexaenoic acid on oestrogen/androgen-induced
      benign prostatic hyperplasia in rats.
AB  - Benign prostatic hyperplasia (BPH) is one of the major disorders of the urinary
      system in elderly men. Docosahexaenoic acid (DHA) is the main component of n-3
      polyunsaturated fatty acids (n-3 PUFAs) and has nerve protective, anti
      inflammatory and tumour-growth inhibitory effects. Here, the therapeutic
      potential of DHA in treating BPH was investigated. Seal oil effectively prevented
      the development of prostatic hyperplasia induced by oestradiol/testosterone in a
      rat model by suppressing the increase of the prostatic index (PI), reducing the
      thickness of the peri-glandular smooth muscle layer, inhibiting the proliferation
      of both prostate epithelial and stromal cells, and downregulating the expression
      of androgen receptor (AR) and oestrogen receptor alpha (ERalpha). An in vitro
      study showed that DHA inhibited the growth of the human prostate stromal cell
      line WPMY-1 and the epithelial cell line RWPE-1 in a dose- and time-dependent
      manner. In both cell lines, the DHA arrested the cell cycle in the G2/M phase. In
      addition, DHA also reduced the expression of ERalpha and AR in the WPMY-1 and
      RWPE-1 cells. These results indicate that DHA inhibits the multiplication of
      prostate stromal and epithelial cells through a mechanism that may involve cell
      cycle arrest and the downregulation of ERalpha and AR expression.

PMID- 25849093
TI  - AceCloud: Molecular Dynamics Simulations in the Cloud.
AB  - We present AceCloud, an on-demand service for molecular dynamics simulations.
      AceCloud is designed to facilitate the secure execution of large ensembles of
      simulations on an external cloud computing service (currently Amazon Web
      Services). The AceCloud client, integrated into the ACEMD molecular dynamics
      package, provides an easy-to-use interface that abstracts all aspects of
      interaction with the cloud services. This gives the user the experience that all
      simulations are running on their local machine, minimizing the learning curve
      typically associated with the transition to using high performance computing
      services. 

PMID- 25849094
TI  - The effect of using an audience response system on learning, motivation and
      information retention in the orthodontic teaching of undergraduate dental
      students: a cross-over trial.
AB  - OBJECTIVE: New methods of teaching and learning are constantly being sought in
      the adult learning environment. Audience Response Systems (ARS) have been used in
      many different learning environments, especially in the field of medical
      education. The objective of this investigation was to ascertain the effect of ARS
      use in undergraduate teaching in a UK dental school. DESIGN: A cross-over
      clustered randomized educational trial. SETTING: Leeds Dental Institute.
      PARTICIPANTS: Year 4 undergraduate dental students in orthodontics. METHODS:
      Students at Leeds Dental Institute were taught two different topics within the
      curriculum to test the use of ARS in a cross-over trial. A questionnaire was
      delivered to the test (ARS) and control (non-ARS) groups. RESULTS: The response
      rate to the questionnaires was 89.5% (test group) and 82.9% (control group). The
      ARS enabled students to perform better as shown by knowledge retention (P =
      0.013). Students found the seminar more interesting (P = 0.013), easier to
      concentrate (P = 0.025) and easier to participate in (P = 0.020) when ARS was
      used. When ARS was used, students were more able to answer questions (P<0.0001),
      were more likely to prepare for the seminar (P<0.0001) and significantly
      preferred using ARS (P<0.0001). CONCLUSIONS: ARS was found to significantly
      improve student concentration and participation in small group seminar teaching
      and significantly improved knowledge retention. ARS may be useful in facilitating
      orthodontic teaching in the future.

PMID- 25849096
TI  - An evaluation of nearly-extinct cohort methods for estimating the very elderly
      populations of australia and new zealand.
AB  - The rapid growth of very elderly populations requires accurate population
      estimates up to the highest ages. However, it is recognised that estimates
      derived from census counts are often unreliable. Methods that make use of death
      data have not previously been evaluated for Australia and New Zealand. The aim
      was to evaluate a number of nearly-extinct cohort methods for producing very
      elderly population estimates by age and sex for Australia and New Zealand. The
      accuracy of official estimates was also assessed. Variants of three nearly
      extinct cohort methods, the Survivor Ratio method, the Das Gupta method and a new
      method explicitly allowing for falling mortality over time, were evaluated by
      retrospective application over the period 1976-1996. Estimates by sex and single
      years of age were compared against numbers derived from the extinct cohort
      method. Errors were measured by the Weighted Mean Absolute Percentage Error. It
      is confirmed that for Australian females the Survivor Ratio method constrained to
      official estimates for ages 90+ performed well. However, for Australian males and
      both sexes in New Zealand, more accurate estimates were obtained by constraining
      the Survivor Ratio method to official estimates for ages 85+. Official estimates
      in Australia proved reasonably accurate for ages 90+ but at 100+ they varied
      significantly in accuracy from year to year. Estimates produced by Statistics New
      Zealand in aggregate for ages 90+ proved very accurate. We recommend the use of
      the Survivor Ratio method constrained to official estimates for ages 85+ to
      create very elderly population estimates for Australia and New Zealand. 

PMID- 25849095
TI  - Interneuron epigenomes during the critical period of cortical plasticity:
      Implications for schizophrenia.
AB  - Schizophrenia, a major psychiatric disorder defined by delusions and
      hallucinations, among other symptoms, often with onset in early adulthood, is
      potentially associated with molecular and cellular alterations in parvalbumin
      expressing fast spiking interneurons and other constituents of the cortical
      inhibitory GABAergic circuitry. The underlying mechanisms, including the role of
      disease-associated risk factors operating in adolescence such as drug abuse and
      social stressors, remain incompletely understood. Here, we summarize emerging
      findings from animal models, highlighting the ability of parvalbuminergic
      interneurons (PVI) to induce, during the juvenile period, long-term plastic
      changes in prefrontal and visual cortex, thereby altering perception, cognition
      and behavior in the adult. Of note, molecular alterations in PVI from subjects
      with schizophrenia, including downregulated expression of a subset of GABAergic
      genes, have also been found in juvenile stress models of the disorder. Some of
      the transcriptional alterations observed in schizophrenia postmortem brain could
      be linked to changes in the epigenetic architecture of GABAergic gene promoters,
      including dysregulated DNA methylation, histone modification patterns and
      disruption of promoter-enhancer interactions at site of chromosomal loop
      formations. Therefore, we predict that, in the not-to-distant future, PVI- and
      other cell-type specific epigenomic mappings in the animal model and human brain
      will provide novel insights into the pathophysiology of schizophrenia and related
      psychotic diseases, including the role of cortical GABAergic circuitry in shaping
      long-term plasticity and cognitive function of the cerebral cortex. 

PMID- 25849097
TI  - Plasmodium falciparum susceptibility to standard and potential anti-malarial
      drugs in Dakar, Senegal, during the 2013-2014 malaria season.
AB  - BACKGROUND: In 2006, the Senegalese National Malaria Control Programme
      recommended artemisinin-based combination therapy (ACT) as the first-line
      treatment for uncomplicated malaria. Since the introduction of ACT, there have
      been very few reports on the level of Plasmodium falciparum resistance to anti
      malarial drugs. An ex vivo susceptibility study was conducted on local isolates
      obtained from the Hopital Principal de Dakar (Dakar, Senegal) from November 2013
      to January 2014. METHODS: Eighteen P. falciparum isolates were sussessfully
      assessed for ex vivo susceptibility to chloroquine (CQ), quinine (QN),
      monodesethylamodiaquine (MDAQ), the active metabolite of amodiaquine, mefloquine
      (MQ), lumefantrine (LMF), artesunate (AS), dihydroartemisinin (DHA), the active
      metabolite of artemisinin derivatives, pyronaridine (PND), piperaquine (PPQ),
      and, Proveblue (PVB), a methylene blue preparation, using the HRP2-based ELISA
      test. RESULTS: The prevalence of isolates with reduced susceptibility was 55.6%
      for MQ, 50% for CQ, 5.6% for QN and MDAQ, and 0% for DHA, AS and LMF. The mean
      IC50 for PND, PPQ and PVB were 5.8 nM, 32.2 nM and 5.3 nM, respectively.
      CONCLUSIONS: The prevalence of isolates with a reduced susceptibility to MQ
      remains high and stable in Dakar. Since 2004, the prevalence of CQ resistance
      decreased, but rebounded in 2013 in Dakar. PND, PPQ and PVB showed high in vitro
      activity in P. falciparum parasites from Dakar.

PMID- 25849098
TI  - Electro-response characteristic of starch hydrogel crosslinked with
      Glutaraldehyde.
AB  - The facile synthesis of the starch hydrogel with anisotropic microstructure and
      dynamic behaviors was developed in the presence (A-gel) and absence of DC
      electric field (B-gel). The microstructures of hydrogels were characterized by
      environmental scanning electron microscope. Their electro-responsive property of
      hydrogels was investigated with their storage modulus (G'). The result
      demonstrates that the G' of A-gel is greater than that of B-gel, and the modulus
      of A-gel increases along with the external field, which signifies positive
      electroresponse. In addition, the G' of A-gel and B-gel ((G'(A) and G'(B)) also
      continuously increases with increasing starch concentration, whereas both the
      maximum of modulus increment (DeltaG' = G'(A)-G'(B) ) and that of modulus
      increment sensitivity (DeltaG'/G'(B)) occur with the starch weight fraction at
      around 36.5%. To enhance the electro-responsive effects of the hydrogels,
      dielectric particles were dispersed in the hydrogel. It is found that
      BaTiO3/chitosan core-shell composite particles significantly enhance the
      electroresponse of the hydrogel. The mechanism of the electro-response mode is
      proposed.

PMID- 25849099
TI  - Li adsorption, hydrogen storage and dissociation using monolayer MoS2: an ab
      initio random structure searching approach.
AB  - Utilizing ab initio random structure searching, we investigated Li adsorption on
      MoS2 and hydrogen molecules on Li-decorated MoS2. In contrast to graphene, Li can
      be adsorbed on both sides of MoS2, with even stronger binding than on the single
      side. We found that high coverages of Li can be attained without Li clustering,
      which is essential for hydrogen storage and Li ion batteries. Moreover, regarding
      battery applications, Li diffusion was also found to be easy. The fully-lithiated
      MoS2 can then adsorb H2 with 4.4 wt%. Interestingly, our calculations revealed
      that hydrogen molecules can be dissociated at high Li coverage with a minimal
      energy barrier. We further showed that the dissociated hydrogen atom can readily
      diffuse on the surface, thus keeping the reaction site active. We therefore
      propose that Li-MoS2 could be an inexpensive alternative catalyst to noble metals
      in hydrogen dissociation reactions. 

PMID- 25849100
TI  - A multistep high-content screening approach to identify novel functionally
      relevant target genes in pancreatic cancer.
AB  - In order to foster the systematic identification of novel genes with important
      functional roles in pancreatic cancer, we have devised a multi-stage screening
      strategy to provide a rational basis for the selection of highly relevant novel
      candidate genes based on the results of functional high-content analyses. The
      workflow comprised three consecutive stages: 1) serial gene expression profiling
      analyses of primary human pancreatic tissues as well as a number of in vivo and
      in vitro models of tumor-relevant characteristics in order to identify genes with
      conspicuous expression patterns; 2) use of 'reverse transfection array'
      technology for large-scale parallelized functional analyses of potential
      candidate genes in cell-based assays; and 3) selection of individual candidate
      genes for further in-depth examination of their cellular roles. A total of 14
      genes, among them 8 from "druggable" gene families, were classified as high
      priority candidates for individual functional characterization. As an example to
      demonstrate the validity of the approach, comprehensive functional data on
      candidate gene ADRBK1/GRK2, which has previously not been implicated in
      pancreatic cancer, is presented. 

PMID- 25849101
TI  - Breast cancer biology and ethnic disparities in breast cancer mortality in new
      zealand: a cohort study.
AB  - INTRODUCTION: Indigenous Maori women have a 60% higher breast cancer mortality
      rate compared with European women in New Zealand. We investigated differences in
      cancer biological characteristics and their impact on breast cancer mortality
      disparity between Maori and NZ European women. MATERIALS AND METHODS: Data on
      2849 women with primary invasive breast cancers diagnosed between 1999 and 2012
      were extracted from the Waikato Breast Cancer Register. Differences in
      distribution of cancer biological characteristics between Maori and NZ European
      women were explored adjusting for age and socioeconomic deprivation in logistic
      regression models. Impacts of socioeconomic deprivation, stage and cancer
      biological characteristics on breast cancer mortality disparity between Maori and
      NZ European women were explored in Cox regression models. RESULTS: Compared with
      NZ European women (n=2304), Maori women (n=429) had significantly higher rates of
      advanced and higher grade cancers. Maori women also had non-significantly higher
      rates of ER/PR negative and HER-2 positive breast cancers. Higher odds of
      advanced stage and higher grade remained significant for Maori after adjusting
      for age and deprivation. Maori women had almost a 100% higher age and deprivation
      adjusted breast cancer mortality hazard compared with NZ European women (HR=1.98,
      1.55-2.54). Advanced stage and lower proportion of screen detected cancer in
      Maori explained a greater portion of the excess breast cancer mortality (HR
      reduction from 1.98 to 1.38), while the additional contribution through
      biological differences were minimal (HR reduction from 1.38 to 1.35).
      CONCLUSIONS: More advanced cancer stage at diagnosis has the greatest impact
      while differences in biological characteristics appear to be a minor contributor
      for inequities in breast cancer mortality between Maori and NZ European women.
      Strategies aimed at reducing breast cancer mortality in Maori should focus on
      earlier diagnosis, which will likely have a greater impact on reducing breast
      cancer mortality inequity between Maori and NZ European women.

PMID- 25849102
TI  - Intra-abdominal pressure correlates with extracellular water content.
AB  - BACKGROUND: Secondary increase in intra-abdominal pressure (IAP) may result from
      extra-abdominal pathology, such as massive fluid resuscitation, capillary leak or
      sepsis. All these conditions increase the extravascular water content. The aim of
      this study was to analyze the relationship between IAP and body water volume.
      MATERIAL AND METHODS: Adult patients treated for sepsis or septic shock with
      acute kidney injury (AKI) and patients undergoing elective pharyngolaryngeal or
      orthopedic surgery were enrolled. IAP was measured in the urinary bladder. Total
      body water (TBW), extracellular water content (ECW) and volume excess (VE) were
      measured by whole body bioimpedance. Among critically ill patients, all
      parameters were analyzed over three consecutive days, and parameters were
      evaluated perioperatively in surgical patients. RESULTS: One hundred twenty
      patients were studied. Taken together, the correlations between IAP and VE, TBW,
      and ECW were measured at 408 time points. In all participants, IAP strongly
      correlated with ECW and VE. In critically ill patients, IAP correlated with ECW
      and VE. In surgical patients, IAP correlated with ECW and TBW. IAP strongly
      correlated with ECW and VE in the mixed population. IAP also correlated with VE
      in critically ill patients. ROC curve analysis showed that ECW and VE might be
      discriminative parameters of risk for increased IAP. CONCLUSION: IAP strongly
      correlates with ECW.

PMID- 25849104
TI  - Chiral gold phosphate catalyzed tandem hydroamination/asymmetric transfer
      hydrogenation enables access to chiral tetrahydroquinolines.
AB  - A highly efficient chiral gold phosphate-catalyzed tandem
      hydroamination/asymmetric transfer hydrogenation reaction is described. A series
      of chiral tetrahydroquinolines were obtained in excellent yields and
      enantioselectivities. In this reaction, the gold catalyst enables both the
      hydroamination step as a pi-Lewis acid and the asymmetric hydrogen-transfer
      process as an effective chiral Lewis acid. 

PMID- 25849103
TI  - Parallel action of AtDRB2 and RdDM in the control of transposable element
      expression.
AB  - BACKGROUND: In plants and animals, a large number of double-stranded RNA binding
      proteins (DRBs) have been shown to act as non-catalytic cofactors of DICERs and
      to participate in the biogenesis of small RNAs involved in RNA silencing. We have
      previously shown that the loss of Arabidopsis thaliana's DRB2 protein results in
      a significant increase in the population of RNA polymerase IV (p4) dependent
      siRNAs, which are involved in the RNA-directed DNA methylation (RdDM) process.
      RESULTS: Surprisingly, despite this observation, we show in this work that DRB2
      is part of a high molecular weight complex that does not involve RdDM actors but
      several chromatin regulator proteins, such as MSI4, PRMT4B and HDA19. We show
      that DRB2 can bind transposable element (TE) transcripts in vivo but that drb2
      mutants do not have a significant variation in TE DNA methylation. CONCLUSION: We
      propose that DRB2 is part of a repressive epigenetic regulator complex involved
      in a negative feedback loop, adjusting epigenetic state to transcription level at
      TE loci, in parallel of the RdDM pathway. Loss of DRB2 would mainly result in an
      increased production of TE transcripts, readily converted in p4-siRNAs by the
      RdDM machinery.

PMID- 25849105
TI  - Single-particle absorption spectroscopy by photothermal contrast.
AB  - Removing effects of sample heterogeneity through single-molecule and single
      particle techniques has advanced many fields. While background free luminescence
      and scattering spectroscopy is widely used, recording the absorption spectrum
      only is rather difficult. Here we present an approach capable of recording pure
      absorption spectra of individual nanostructures. We demonstrate the
      implementation of single-particle absorption spectroscopy on strongly scattering
      plasmonic nanoparticles by combining photothermal microscopy with a
      supercontinuum laser and an innovative calibration procedure that accounts for
      chromatic aberrations and wavelength-dependent excitation powers. Comparison of
      the absorption spectra to the scattering spectra of the same individual gold
      nanoparticles reveals the blueshift of the absorption spectra, as predicted by
      Mie theory but previously not detectable in extinction measurements that measure
      the sum of absorption and scattering. By covering a wavelength range of 300 nm,
      we are furthermore able to record absorption spectra of single gold nanorods with
      different aspect ratios. We find that the spectral shift between absorption and
      scattering for the longitudinal plasmon resonance decreases as a function of
      nanorod aspect ratio, which is in agreement with simulations. 

PMID- 25849107
TI  - Amperometric detection of extended-spectrum beta-lactamase activity: application
      to the characterization of resistant E. coli strains.
AB  - The amperometric detection of extended-spectrum beta-lactamase (ESBL) with carbon
      screen-printed sensors was investigated in the presence of the Nitrocefin, a
      commercially-available beta-lactamase chromogenic cephalosporin substrate. Using
      an ESBL isolated from a clinical sample, it was shown for the first time that the
      intensity of a specific anodic pic current (EP = ~+0.3 V vs. Ag/AgCl) resulting
      from the catalytic hydrolysis of the beta-lactam ring was proportional to the
      amount of ESBL. The proof-of-principle of a novel susceptibility assay for the
      rapid and accurate identification of ESBL- producing bacteria was then
      demonstrated. The detection scheme relied on (i) the culture of the sample in a
      medium containing the cefotaxime supplemented or not with the clavulanic acid
      inhibitor to allow the specific determination of ESBL producers (ii) followed by
      the incubation of the bacteria with the Nitrocefin and (iii) the measurement of
      the enzyme product by cyclic voltammetry. The amperometric assay was further
      applied to the characterization of E. coli strains and to the quantification of
      the ESBL producers. A detection limit of 5 * 10(4) cfu mL(-1) ESBL-producing E.
      coli was achieved after a 10 min incubation time. In contrast to the approved
      routine assays, the electrochemical approach, which did not require isolated
      colonies to be performed, provided quantified results regarding ESBL activity
      within a few hours. Finally, owing to its cost-effectiveness, portability and
      simplicity, this test holds great promise for clinical and environmental
      applications. 

PMID- 25849106
TI  - Invasive lobular carcinoma of the breast: morphology, biomarkers and 'omics.
AB  - Invasive lobular carcinoma of the breast is the most common 'special'
      morphological subtype of breast cancer, comprising up to 15% of all cases.
      Tumours are generally of a good prognostic phenotype, being low histological
      grade and low mitotic index, hormone receptor positive and HER2, p53 and basal
      marker negative, and with a generally good response to endocrine therapy. Despite
      this, clinicians face countless challenges in the diagnosis and long-term
      management of patients, as they encounter a tumour that can be difficult to
      detect through screening, elicits a very invasive nature, a propensity for
      widespread metastatic colonisation and, consequently, in some studies a worse
      long-term poor outcome compared with invasive carcinoma of no special type. Here
      we review the morphological and molecular features that underpin the disparate
      biological and clinical characteristics of this fascinating tumour type. 

PMID- 25849108
TI  - Orthodontic treatment of a particular subgroup of children with special health
      care needs, children with craniofacial anomalies: An analysis of treatment length
      and clinical outcome.
AB  - OBJECTIVE: To analyze any differences in the orthodontic treatment between
      children belonging to a particular subgroup of subjects with special health care
      needs (SHCN), children with craniofacial anomalies (CFA), and children not
      diagnosed with SHCN (NO SHCN). MATERIALS AND METHODS: The study sample consisted
      of 50 children with SHCN and a confirmed diagnosis of CFA (SHCN/CFA); the control
      group consisted of 50 NO SHCN children fully matched for age, gender, and type of
      appliance used. The differences between the two groups were analyzed
      retrospectively: pre-, posttreatment scores, and score reduction of the Peer
      Assessment Rating Index (PAR), dental health component (DHC), and aesthetic
      component (AC) of Orthodontic Treatment Need Index (IOTN), number of
      appointments, number of simple or complex chair-time appointments, overall
      treatment time, and age at treatment start and end. RESULTS: There were no
      statistically significant differences between the SHCN/CFA and NO SHCN groups for
      number of appointments, overall treatment time, age at treatment start, and age
      at treatment end (P  =  .682, .458, .535, and .675, respectively). There were
      statistically significant differences between groups in PAR, DHC, AC pre- and
      posttreatment, and number of simple and complex chair-time appointments (P  = 
      .030 and .000; .020 and .023; .000 and .000; .043; and .037; respectively). The
      reduction of PAR, DHC, and AC scores was not significantly different between
      groups (P  =  .060, .765, and .825, respectively). CONCLUSION: The treatment of
      children with SHCN, in general, and with CFA, in particular, on the one hand
      involves a higher rate of using complex chair time appointments and an inferior
      treatment outcome, by the other side implies an overall treatment time and a
      reduction of PAR, DHC or AC scores similar to the treatment of children not
      diagnosed with SHCN.

PMID- 25849109
TI  - Changes in the endurance shuttle walk test in COPD patients with chronic
      respiratory failure after pulmonary rehabilitation: the minimal important
      difference obtained with anchor- and distribution-based method.
AB  - BACKGROUND: Although the endurance shuttle walk test (ESWT) has proven to be
      responsive to change in exercise capacity after pulmonary rehabilitation (PR) for
      COPD, the minimally important difference (MID) has not yet been established. We
      aimed to establish the MID of the ESWT in patients with severe COPD and chronic
      hypercapnic respiratory failure following PR. METHODS: Data were derived from a
      randomized controlled trial, investigating the value of noninvasive positive
      pressure ventilation added to PR. Fifty-five patients with stable COPD, GOLD
      stage IV, with chronic respiratory failure were included (mean (SD) FEV1 31.1
      (12.0) % pred, age 62 (9) y). MID estimates of the ESWT in seconds, percentage
      and meters change were calculated with anchor based and distribution based
      methods. Six minute walking distance (6MWD), peak work rate on bicycle ergometry
      (Wpeak) and Chronic Respiratory Questionnaire (CRQ) were used as anchors and
      Cohen's effect size was used as distribution based method. RESULTS: The estimated
      MID of the ESWT with the different anchors ranged from 186-199 s, 76-82% and 154
      164 m. Using the distribution based method the MID was 144 s, 61% and 137 m.
      CONCLUSIONS: Estimates of the MID for the ESWT after PR showed only small
      differences using different anchors in patients with COPD and chronic respiratory
      failure. Therefore we recommend using a range of 186-199 s, 76-82% or 154-164 m
      as MID of the ESWT in COPD patients with chronic respiratory failure. Further
      research in larger populations should elucidate whether this cut-off value is
      also valid in other COPD populations and with other interventions. TRIAL
      REGISTRATION: ClinicalTrials.Gov (ID NCT00135538).

PMID- 25849110
TI  - Recombinant hamster oviductin is biologically active and exerts positive effects
      on sperm functions and sperm-oocyte binding.
AB  - Studies carried out in several mammalian species suggest that oviductin, also
      known as oviduct-specific glycoprotein or OVGP1, plays a key role in sperm
      capacitation, fertilization, and development of early embryos. In the present
      study, we used recombinant DNA technology to produce, for the first time,
      recombinant hamster OVGP1 (rHamOVGP1) in human embryonic kidney 293 (HEK293)
      cells. rHamOVGP1 secreted in the culture medium was purified by affinity
      chromatography. The resulting protein migrated as a poly-dispersed band of 160
      350 kDa on SDS-PAGE corresponding to the molecular mass of the native HamOVGP1.
      Subsequent mass spectrometric analysis of the purified rHamOVGP1 confirmed its
      identity as HamOVGP1. Immunocytochemistry demonstrated binding of rHamOVGP1 to
      the mid-piece and head of hamster sperm and to the zona pellucida (ZP) of ovarian
      oocytes. In vitro functional experiments showed that addition of rHamOVGP1 in the
      capacitation medium further enhanced tyrosine phosphorylation of two sperm
      proteins of approximately 75 kDa and 83 kDa in a time-dependent manner. After 3
      hours of incubation in the presence of rHamOVGP1, a significant increase in
      acrosome reaction was measured. Pretreatment of either sperm or oocyte with 20
      MUg/ml of rHamOVGP1 prior to sperm-egg binding assay significantly increased the
      number of sperm bound to the ZP. Addition of rHamOVGP1 in the medium during sperm
      egg binding with either oocyte or sperm pretreated with rHamOVGP1 also saw an
      increase in the number of sperm bound to ZP. In all experimental conditions, the
      effect of rHamOVGP1 on sperm-oocyte binding was negated by the addition of
      monoclonal anti-HamOVGP1 antibody. The successful production and purification of
      a biologically active rHamOVGP1 will allow further exploration of the function of
      this glycoprotein in reproductive function. 

PMID- 25849111
TI  - Estimated dietary dioxin exposure and breast cancer risk among women from the
      French E3N prospective cohort.
AB  - INTRODUCTION: Dioxins are environmental and persistent pollutants mostly emitted
      from combustion facilities (e.g. waste incinerators, metal and cement
      industries). Known to be endocrine disrupting chemicals, dioxins are suspected to
      increase breast cancer (BC) risk. Although diet is considered the primary source
      of dioxin exposure, no previous study has been published on dietary dioxin
      exposure in relation to BC risk. We aimed to assess dietary dioxin exposure among
      women from the E3N cohort and estimate BC risk associated with this exposure.
      METHODS: The study included 63,830 women from the E3N cohort who completed a diet
      history questionnaire (DHQ) in 1993 and were followed until 2008. Dietary dioxin
      exposure was estimated by combining consumption data from the E3N DHQ and food
      dioxin contamination data from a French national monitoring program. Hazard
      ratios (HR) and 95% confidence intervals (CI) were estimated by Cox models
      adjusted for BC risk factors. RESULTS: Mean dietary dioxin exposure was estimated
      at 1.3 +/- 0.4 pg/kg body weight (BW)/day. A 0.4 pg/kg BW/d increase in dioxin
      intake was not associated with overall BC risk (HR = 1.00; 95% CI: 0.96, 1.05). A
      significant decrease in risk of estrogen receptor negative (ER-)/progesterone
      receptor negative (PR-) tumors was observed among post-menopausal women in the
      upper quartile of estimated dioxin intake (HR for Q4 vs. Q1: 0.65; 95% CI: 0.45,
      0.96; P for trend across quartiles = 0.0463). CONCLUSIONS: Overall, no
      association between estimated dietary dioxin exposure and BC risk was found among
      E3N women. Further studies should include both dietary and environmental
      exposures to determine whether low-dose dioxin exposure is associated with BC
      risk.

PMID- 25849112
TI  - Analysis of new isolates reveals new genome organization and a hypervariable
      region in infectious myonecrosis virus (IMNV).
AB  - Infectious myonecrosis virus (IMNV) has been the cause of many losses in shrimp
      farming since 2002, when the first myonecrosis outbreak was reported at
      Brazilian's northeast coast. Two additional genomes of Brazilian IMNV isolates
      collected in 2009 and 2013 were sequenced and analyzed in the present study. The
      sequencing revealed extra 643 bp and 22 bp, at 5' and 3' ends of IMNV genome
      respectively, confirming that its actual size is at least 8226 bp long.
      Considering these additional sequences in genome extremities, ORF1 can starts at
      nt 470, encoding a 1708 aa polyprotein. Computational predictions reveal two stem
      loops and two pseudoknots in the 5' end and a putative stem loop and a slippery
      motif located at 3' end, indicating that these regions can be involved in the
      start and termination of translation. Through a careful phylogenetic analysis, a
      higher genetic variability among Brazilian isolates could be observed, comparing
      with Indonesian IMNV isolates. It was also observed that the most variable region
      of IMNV genome is located in the first half of ORF1, coinciding with a region
      which probably encodes the capsid protrusions. The results presented here are a
      starting point to elucidate the viral's translational regulation and the
      mechanisms involved in virulence.

PMID- 25849114
TI  - A predictive approach to CVD of crystalline layers of TMDs: the case of MoS2.
AB  - Layered transition metal dichalcogenides (TMDs), such as MoS2, are candidate
      materials for next generation 2-D electronic and optoelectronic devices. The
      ability to grow uniform, crystalline, atomic layers over large areas is the key
      to developing such technology. We report a chemical vapor deposition (CVD)
      technique which yields n-layered MoS2 on a variety of substrates. A generic
      approach suitable to all TMDs, involving thermodynamic modeling to identify the
      appropriate CVD process window, and quantitative control of the vapor phase
      supersaturation, is demonstrated. All reactant sources in our method are outside
      the growth chamber, a significant improvement over vapor-based methods for atomic
      layers reported to date. The as-deposited layers are p-type, due to Mo
      deficiency, with field effect and Hall hole mobilities of up to 2.4 cm(2) V(-1)
      s(-1) and 44 cm(2) V(-1) s(-1) respectively. These are among the best reported
      yet for CVD MoS2. 

PMID- 25849113
TI  - An economic evaluation of conception strategies for heterosexual serodiscordant
      couples where the male partner is HIV-positive.
AB  - BACKGROUND: To conduct an economic evaluation of the three commonly used
      interventions that reduce sexual HIV transmission when an HIV-negative female
      aims to conceive with an HIV-positive male on combination antiretroviral therapy
      (condomless sex restricted to timed ovulation [CS], sperm washing with
      intrauterine insemination [SW] and condomless sex restricted to timed ovulation
      with pre-exposure prophylaxis [CS-PrEP]). As SW and CS-PrEP are only privately
      available for pregnancy planning for this population in Canada, this study was
      conducted to inform policy decisions concerning potential public health insurance
      coverage, as well as to inform fertility counselling in settings with adequate
      combination antiretroviral therapy access globally. METHODS: We developed a
      cohort Markov model with a lifetime horizon and used the perspective of Ontario's
      Ministry of Health (MOH). Input parameters were drawn from literature, the MOH's
      Schedule of Benefits and a time trade-off questionnaire designed for this study.
      Outcome measures included quality-adjusted life-years and incremental cost
      effectiveness. Costs and benefits were discounted at annual rates of 3%. Costs
      were reported in Canadian 2013 dollars and an exchange rate of 1 USD to 1.066 CND
      was applied where necessary. Sensitivity analysis assessed the uncertainty of
      model parameters. RESULTS: The base case analysis found that CS-PrEP and SW were
      each more costly and less effective at conception than CS. The results were
      robust in the sensitivity analysis and suggest that CS is the dominant conception
      strategy in this population. CONCLUSIONS: Neither CS-PrEP nor SW represent better
      value for money relative to CS as a conception option for HIV-discordant couples
      with positive male partners. Based on these findings, CS-PrEP and SW cannot be
      recommended for public-funding in developed countries.

PMID- 25849115
TI  - Effectiveness of Rice Agricultural Waste, Microbes and Wetland Plants in the
      Removal of Reactive Black-5 Azo Dye in Microcosm Constructed Wetlands.
AB  - Azo dyes are commonly generated as effluent pollutants by dye using industries,
      causing contamination of surface and ground water. Various strategies are
      employed to treat such wastewater; however, a multi-faceted treatment strategy
      could be more effective for complete removal of azo dyes from industrial effluent
      than any single treatment. In the present study, rice husk material was used as a
      substratum in two constructed wetlands (CWs) and augmented with microorganisms in
      the presence of wetland plants to effectively treat dye-polluted water. To
      evaluate the efficiency of each process the study was divided into three levels,
      i.e., adsorption of dye onto the substratum, phytoremediation within the CW and
      then bioremediation along with the previous two processes in the augmented CW.
      The adsorption process was helpful in removing 50% dye in presence of rice husk
      while 80% in presence of rice husk biocahr. Augmentation of microorganisms in CW
      systems has improved dye removal efficiency to 90%. Similarly presence of
      microorganisms enhanced removal of total nitrogen (68% 0 and Total phosphorus
      (75%). A significant improvement in plant growth was also observed by measuring
      plant height, number of leaves and leave area. These findings suggest the use of
      agricultural waste as part of a CW substratum can provide enhanced removal of
      textile dyes. 

PMID- 25849116
TI  - Optical protein detection based on magnetic clusters rotation.
AB  - In this paper we present a simple method to quantify aggregates of 200nm magnetic
      particles. This method relies on the optical and magnetic anisotropy of particle
      aggregates, whereas dispersed particles are optically isotropic. We orientate
      aggregates by applying short pulses of a magnetic field, and we measure optical
      density variation directly linked to this reorientation. By computing the
      scattering efficiency of doublets and singlets, we demonstrate the absolute
      quantification of a few % of doublets in a well dispersed suspension. More
      generally, these optical variations are related to the aggregation state of the
      sample. This method can be easily applied to an agglutination assay, where target
      proteins induce aggregation of colloidal particles. By observing only aligned
      clusters, we increase sensitivity and we reduce the background noise as compared
      to a classical agglutination assay: we obtain a detection limit on the C-reactive
      protein of less than 3pM for a total assay time of 10min. 

PMID- 25849117
TI  - Stepwise catalytic mechanism via short-lived intermediate inferred from combined
      QM/MM MERP and PES calculations on retaining glycosyltransferase ppGalNAcT2.
AB  - The glycosylation of cell surface proteins plays a crucial role in a multitude of
      biological processes, such as cell adhesion and recognition. To understand the
      process of protein glycosylation, the reaction mechanisms of the participating
      enzymes need to be known. However, the reaction mechanism of retaining
      glycosyltransferases has not yet been sufficiently explained. Here we
      investigated the catalytic mechanism of human isoform 2 of the retaining
      glycosyltransferase polypeptide UDP-GalNAc transferase by coupling two different
      QM/MM-based approaches, namely a potential energy surface scan in two distance
      difference dimensions and a minimum energy reaction path optimisation using the
      Nudged Elastic Band method. Potential energy scan studies often suffer from
      inadequate sampling of reactive processes due to a predefined scan coordinate
      system. At the same time, path optimisation methods enable the sampling of a
      virtually unlimited number of dimensions, but their results cannot be
      unambiguously interpreted without knowledge of the potential energy surface. By
      combining these methods, we have been able to eliminate the most significant
      sources of potential errors inherent to each of these approaches. The structural
      model is based on the crystal structure of human isoform 2. In the QM/MM method,
      the QM region consists of 275 atoms, the remaining 5776 atoms were in the MM
      region. We found that ppGalNAcT2 catalyzes a same-face nucleophilic substitution
      with internal return (SNi). The optimized transition state for the reaction is
      13.8 kcal/mol higher in energy than the reactant while the energy of the product
      complex is 6.7 kcal/mol lower. During the process of nucleophilic attack, a
      proton is synchronously transferred to the leaving phosphate. The presence of a
      short-lived metastable oxocarbenium intermediate is likely, as indicated by the
      reaction energy profiles obtained using high-level density functionals. 

PMID- 25849118
TI  - Invariant natural killer T cells treated with rapamycin or transforming growth
      factor-beta acquire a regulatory function and suppress T effector lymphocytes.

PMID- 25849119
TI  - An imbalance between innate and adaptive immune cells at the maternal-fetal
      interface occurs prior to endotoxin-induced preterm birth.
AB  - Preterm birth (PTB) is the leading cause of neonatal morbidity and mortality
      worldwide. A transition from an anti-inflammatory state to a pro-inflammatory
      state in the mother and at the maternal-fetal interface has been implicated in
      the pathophysiology of microbial-induced preterm labor. However, it is unclear
      which immune cells mediate this transition. We hypothesized that an imbalance
      between innate and adaptive immune cells at the maternal-fetal interface will
      occur prior to microbial-induced preterm labor. Using an established murine model
      of endotoxin-induced PTB, our results demonstrate that prior to delivery there is
      a reduction of CD4+ regulatory T cells (Tregs) in the uterine tissues. This
      reduction is neither linked to a diminished number of Tregs in the spleen, nor to
      an impaired production of IL10, CCL17, or CCL22 by the uterine tissues. Endotoxin
      administration to pregnant mice does not alter effector CD4+ T cells at the
      maternal-fetal interface. However, it causes an imbalance between Tregs (CD4+ and
      CD8+), effector CD8+ T cells, and Th17 cells in the spleen. In addition,
      endotoxin administration to pregnant mice leads to an excessive production of
      CCL2, CCL3, CCL17, and CCL22 by the uterine tissues as well as abundant
      neutrophils. This imbalance in the uterine microenvironment is accompanied by
      scarce APC-like cells such as macrophages and MHC II+ neutrophils. Collectively,
      these results demonstrate that endotoxin administration to pregnant mice causes
      an imbalance between innate and adaptive immune cells at the maternal-fetal
      interface.

PMID- 25849120
TI  - Reversal of B-cell hyperactivation and functional impairment is associated with
      HBsAg seroconversion in chronic hepatitis B patients.
AB  - B cells play an important role in the clearance of hepatitis B virus (HBV) and
      protection against reinfection. However, the functional characteristics of these
      cells that are associated with the outcome of chronic HBV infection remain
      unknown. We comprehensively investigated the frequency, phenotype, and function
      of peripheral B-cell subsets from CHB patients in different phases: immune
      tolerance (IT), immune activation (IA), immune clearance (IC), responders with
      HBsAg seroconversion (resolved patients, RP), and healthy controls (HC). IA
      patients displayed lower percentages of peripheral blood memory B cells compared
      with the other groups. Overall polyclonal activation of B cells, indicated by
      higher levels of activation markers and secretion of IgG and IgM, was observed in
      IA patients. This B-cell hyperactivation could be induced by increased IFN-alpha
      and soluble CD40 ligands in IA patients. Notably, the expression of the co
      stimulator molecule CD80 and serum HBsAb and the frequency of HBsAg-specific B
      cells were significantly decreased in IT, IA, and IC patients compared with HC
      subjects. More importantly, the B-cell hyperactivation, co-stimulatory molecule
      downregulation and HBsAg-specific B-cell impairment were reversed in RP patients.
      The reversal of B-cell hyperactivation and functional impairment is associated
      with HBsAg seroconversion in chronic hepatitis B patients.

PMID- 25849122
TI  - Correction: a genomic screen revealing the importance of vesicular trafficking
      pathways in genome maintenance and protection against genotoxic stress in diploid
      Saccharomyces cerevisiae cells.

PMID- 25849121
TI  - AID expression increased by TNF-alpha is associated with class switch
      recombination of Igalpha gene in cancers.
AB  - Recently, immunoglobulins (Igs) were unexpectedly found to be expressed in
      epithelial cancers. Immunoglobulin class switching or class switch recombination
      (CSR) is a natural biological process that alters a B cell's production of
      antibodies (immunoglobulins) from one class to another. However, the mechanism of
      CSR of Ig genes in cancer is still unknown. Here, we confirmed by detecting the
      hallmark of CSR that the Igalpha gene in cancer underwent CSR. Then we focused on
      activation-induced cytidine deaminase (AID), a crucial factor for initiating CSR.
      Further studies using tumor necrosis factor (TNF)-alpha stimulation and specific
      inhibitor of NF-kappaB revealed that TNF-alpha could increase AID expression
      through NF-kappaB signaling. Finally, we demonstrated that AID could co-localize
      with protein kinase A and bind to the switching (Salpha) region of the Igalpha
      gene. Overexpression of AID obviously enhanced Igalpha heavy chain expression and
      its binding ability to the Salpha region. These findings indicated that TNF-alpha
      induced AID expression is involved with CSR in cancer.

PMID- 25849123
TI  - Tassel removal positively affects biomass production coupled with significantly
      increasing stem digestibility in switchgrass.
AB  - In this study, tassels of Cave-in-Rock (upland) and Alamo (lowland) were removed
      at or near tassel emergence to explore its effects on biomass production and
      quality. Tassel-removed (TR) Cave-in-Rock and Alamo both exhibited a significant
      (P<0.05) increase in plant heights (not including tassel length), tiller number,
      and aboveground biomass dry weight (10% and 12%, 30% and 13%, 13% and 18%,
      respectively by variety) compared to a control (CK) treatment. Notably, total
      sugar yields of TR Cave-in-Rock and Alamo stems increased significantly (P<0.05
      or 0.01) by 19% and 19%, 21% and 14%, 52% and 18%, respectively by variety,
      compared to those of control switchgrass under 3 treatments by direct enzymatic
      hydrolysis (DEH), enzymatic hydrolysis after 1% NaOH pretreatment (EHAL) and
      enzymatic hydrolysis after 1% H2SO4 pretreatment (EHAC). These differences were
      mainly due to significantly (P<0.05 or 0.01) higher cellulose content, lower
      cellulose crystallinity indexes (CrI) caused by higher arabinose (Ara)
      substitution in xylans, and lower S/G ratio in lignin. However, the increases of
      nitrogen (N) and sulphur (S) concentration negatively affects the combustion
      quality of switchgrass aboveground biomass. This work provides information for
      increasing biomass production and quality in switchgrass and also facilitates the
      inhibition of gene dispersal of switchgrass in China. 

PMID- 25849124
TI  - Antibodies to group A streptococcal virulence factors, SIC and DRS, increase
      predilection to GAS pyoderma.
AB  - BACKGROUND: Streptococcus pyogenes (group A streptococcus; GAS) is an etiological
      agent for pharyngitis, pyoderma, and invasive infections in humans. Pharyngitis
      and pyoderma may lead to serious immune sequelae such as rheumatic heart disease
      and post-streptococcal glomerulonephritis (PSGN). Streptococcal Inhibitor of
      Complement (SIC) and its orthologue, distantly related to SIC (DRS), are
      virulence factors expressed by only four of more than 100 M types of GAS. These
      four types (M1, M57, M12 and M55) are among the M types, which are associated
      with PSGN. In several populations PSGN has been shown to be a risk factor for
      chronic kidney disease (CKD) and end-stage renal disease (ESRD). Previous studies
      showed SIC or DRS antibody-prevalence was associated with PSGN, and
      seroprevalence of SIC antibodies is significantly high among CKD and ESRD
      patients in Mumbai. METHODS: Streptococcal isolates recovered from GAS pyoderma
      cases were typed. Seropositivity for SIC and DRS antibodies in subjects with
      pyoderma, PSGN pediatric cases, age matched healthy controls and non-GAS pyoderma
      cases were determined. RESULTS: We confirm in this study an association between
      seroprevalence to SIC and DRS antibodies, and PSGN in Mumbai population despite
      low point prevalence of M1, M12, M55 and M57. In addition we extended the study
      to GAS-pyoderma and non-GAS pyoderma cases. To our surprise, we found a positive
      association between the seroprevalence to SIC and DRS antibodies, and GAS
      pyoderma owing to infection with diverse M types. The mechanism of increased
      predisposition to pyoderma owing to infection by diverse GAS among SIC or DRS
      antibody-positive population is not clear. Nonetheless, our findings could be
      explained by a phenomenon akin to antibody-dependent enhancement (ADE).
      CONCLUSIONS: This is the first report showing a small number of GAS M types
      conferring predisposition to pyoderma by diverse types. Implications of this ADE
      like phenomenon are discussed in the light of evolutionary advantage to GAS,
      vaccine design and control of renal diseases.

PMID- 25849125
TI  - Early modern humans and morphological variation in Southeast Asia: fossil
      evidence from Tam Pa Ling, Laos.
AB  - Little is known about the timing of modern human emergence and occupation in
      Eastern Eurasia. However a rapid migration out of Africa into Southeast Asia by
      at least 60 ka is supported by archaeological, paleogenetic and
      paleoanthropological data. Recent discoveries in Laos, a modern human cranium
      (TPL1) from Tam Pa Ling's cave, provided the first evidence for the presence of
      early modern humans in mainland Southeast Asia by 63-46 ka. In the current study,
      a complete human mandible representing a second individual, TPL 2, is described
      using discrete traits and geometric morphometrics with an emphasis on determining
      its population affinity. The TPL2 mandible has a chin and other discrete traits
      consistent with early modern humans, but it retains a robust lateral corpus and
      internal corporal morphology typical of archaic humans across the Old World. The
      mosaic morphology of TPL2 and the fully modern human morphology of TPL1 suggest
      that a large range of morphological variation was present in early modern human
      populations residing in the eastern Eurasia by MIS 3. 

PMID- 25849127
TI  - Correction: the EJC binding and dissociating activity of PYM is regulated in
      Drosophila.

PMID- 25849126
TI  - Hybrid polymer-lipid films as platforms for directed membrane protein insertion.
AB  - Hybrids composed of amphiphilic block copolymers and lipids constitute a new
      generation of biological membrane-inspired materials. Hybrid membranes resulting
      from self-assembly of lipids and polymers represent adjustable models for
      interactions between artificial and natural membranes, which are of key
      importance, e.g., when developing systems for drug delivery. By combining
      poly(dimethylsiloxane)-block-poly(2-methyl-2-oxazoline) amphiphilic copolymers
      (PDMS-b-PMOXA) with various phospholipids, we obtained hybrid films with
      modulated properties and topology, based on phase separation, and the formation
      of distinct domains. By understanding the factors driving the phase separation in
      these hybrid lipid-polymer films, we were able to use them as platforms for
      directed insertion of membrane proteins. Tuning the composition of the polymer
      lipids mixtures favored successful insertion of membrane proteins with desired
      topological distributions (in polymer or/and lipid regions). Controlled insertion
      and location of membrane proteins in hybrid films make these hybrids ideal
      candidates for numerous applications where specific spatial functionality is
      required. 

PMID- 25849128
TI  - Adverse life events and allele-specific methylation of the serotonin transporter
      gene (SLC6A4) in adolescents: the TRAILS study.
AB  - OBJECTIVES: Adverse life events increase vulnerability to affective disorders
      later in life, possibly mediated by methylation of the serotonin transporter gene
      (SLC6A4). We investigated the relationship of SLC6A4 methylation with various
      types of adversity (perinatal adversity, traumatic youth experiences and
      stressful life events [SLEs]), as well as with the timing of SLEs (during
      childhood [0-11 years] or during adolescence [12-15 years]). In addition, we
      investigated whether different serotonin-transporter-linked polymorphic region
      genotypes were equally sensitive to SLE-related methylation. METHODS: In a
      population sample of 939 adolescents (mean age = 16.2 years), we assessed SLC6A4
      methylation, SLC6A4 functionality (serotonin-transporter-linked polymorphic
      region "long" and "short" alleles, and rs25531), and adverse life events.
      RESULTS: Only a higher number of SLEs was positively associated with higher
      SLC6A4 methylation (B = 0.11, p = .011). Adolescent SLEs were associated with
      higher SLC6A4 methylation (B = 0.13, p = .004) independently of childhood SLEs (B
      = 0.02, p = .57). L-allele homozygotes showed a greater impact of SLEs on
      methylation (B = 0.37, p < .001) than did s-allele carriers (B = 0.04, p = .66),
      resulting in higher levels of SLC6A4 methylation for l-allele homozygotes among
      those experiencing high levels of SLEs. CONCLUSIONS: Our findings demonstrate a
      higher level of SLC6A4 methylation after SLEs in adolescents, with a more
      pronounced association for SLEs during adolescence than during childhood.
      Considering the allele-specific sensitivity of SLC6A4 methylation to SLEs, this
      study may help clarify the role of SLC6A4 in the development of affective
      disorders.

PMID- 25849129
TI  - Longitudinal associations between depression, anxiety, pain, and pain-related
      disability in chronic pain patients.
AB  - OBJECTIVE: The current study sets out to examine the longitudinal relationship
      between pain, pain-related disability, and symptoms of depression and anxiety.
      The latter symptoms are highly prevalent in chronic pain and seriously impede
      functioning and quality of life. Nevertheless, the direction of the relationship
      involving these variables among individuals with chronic pain is still unclear.
      METHODS: Four-hundred twenty-eight individuals with chronic pain (238 women, mean
      age 54.84 years, mean pain duration 85.21 months) treated at two pain clinics
      completed questionnaires regarding their pain (Short-Form McGill Pain
      Questionnaire), depression (Center for Epidemiological Studies-Depression Scale),
      state anxiety (State-Trait Anxiety Inventory), and pain-related disability (Pain
      Disability Index) at four time points, with an average of 5 months between
      measurements. Cross-lagged, structural equation modeling analyses were performed,
      enabling the examination of longitudinal associations between the variables.
      RESULTS: Significant symptoms of both depression and anxiety were reported by
      more than half of the sample on all waves. A latent depression/anxiety variable
      longitudinally predicted pain (beta = .27, p < .001) and pain-related disability
      (beta = .38, p < .001). However, neither pain (beta = .10, p = .126) nor pain
      related disability (beta = -.01, p = .790) predicted depression/anxiety.
      CONCLUSIONS: Among adult patients with chronic pain treated at specialty pain
      clinics, high levels of depression and anxiety may worsen pain and pain-related
      disability.

PMID- 25849130
TI  - Studying clonal dynamics in response to cancer therapy using high-complexity
      barcoding.
AB  - Resistance to cancer therapies presents a significant clinical challenge. Recent
      studies have revealed intratumoral heterogeneity as a source of therapeutic
      resistance. However, it is unclear whether resistance is driven predominantly by
      pre-existing or de novo alterations, in part because of the resolution limits of
      next-generation sequencing. To address this, we developed a high-complexity
      barcode library, ClonTracer, which enables the high-resolution tracking of more
      than 1 million cancer cells under drug treatment. In two clinically relevant
      models, ClonTracer studies showed that the majority of resistant clones were part
      of small, pre-existing subpopulations that selectively escaped under therapeutic
      challenge. Moreover, the ClonTracer approach enabled quantitative assessment of
      the ability of combination treatments to suppress resistant clones. These
      findings suggest that resistant clones are present before treatment, which would
      make up-front therapeutic combinations that target non-overlapping resistance a
      preferred approach. Thus, ClonTracer barcoding may be a valuable tool for
      optimizing therapeutic regimens with the goal of curative combination therapies
      for cancer. 

PMID- 25849131
TI  - Resveratrol activates duodenal Sirt1 to reverse insulin resistance in rats
      through a neuronal network.
AB  - Resveratrol improves insulin sensitivity and lowers hepatic glucose production
      (HGP) in rat models of obesity and diabetes, but the underlying mechanisms for
      these antidiabetic effects remain elusive. One process that is considered a key
      feature of resveratrol action is the activation of the nicotinamide adenine
      dinucleotide (NAD(+))-dependent deacetylase sirtuin 1 (SIRT1) in various tissues.
      However, the low bioavailability of resveratrol raises questions about whether
      the antidiabetic effects of oral resveratrol can act directly on these tissues.
      We show here that acute intraduodenal infusion of resveratrol reversed a 3 d high
      fat diet (HFD)-induced reduction in duodenal-mucosal Sirt1 protein levels while
      also enhancing insulin sensitivity and lowering HGP. Further, we found that
      duodenum-specific knockdown of Sirt1 expression for 14 d was sufficient to induce
      hepatic insulin resistance in rats fed normal chow. We also found that the
      glucoregulatory role of duodenally acting resveratrol required activation of
      Sirt1 and AMP-activated protein kinase (Ampk) in this tissue to initiate a gut
      brain-liver neuronal axis that improved hypothalamic insulin sensitivity and in
      turn, reduced HGP. In addition to the effects of duodenally acting resveratrol in
      an acute 3 d HFD-fed model of insulin resistance, we also found that short-term
      infusion of resveratrol into the duodenum lowered HGP in two other rat models of
      insulin resistance--a 28 d HFD-induced model of obesity and a nicotinamide (NA)
      streptozotocin (STZ)-HFD-induced model of mild type 2 diabetes. Together, these
      studies highlight the therapeutic relevance of targeting duodenal SIRT1 to
      reverse insulin resistance and improve glucose homeostasis in obesity and
      diabetes.

PMID- 25849132
TI  - An RNAi therapeutic targeting antithrombin to rebalance the coagulation system
      and promote hemostasis in hemophilia.
AB  - Hemophilia A and B are inherited bleeding disorders characterized by deficiencies
      in procoagulant factor VIII (FVIII) or factor IX (FIX), respectively. There
      remains a substantial unmet medical need in hemophilia, especially in patients
      with inhibitory antibodies against replacement factor therapy, for novel and
      improved therapeutic agents that can be used prophylactically to provide
      effective hemostasis. Guided by reports suggesting that co-inheritance of
      prothrombotic mutations may ameliorate the clinical phenotype in hemophilia, we
      developed an RNA interference (RNAi) therapeutic (ALN-AT3) targeting antithrombin
      (AT) as a means to promote hemostasis in hemophilia. When administered
      subcutaneously, ALN-AT3 showed potent, dose-dependent, and durable reduction of
      AT levels in wild-type mice, mice with hemophilia A, and nonhuman primates
      (NHPs). In NHPs, a 50% reduction in AT levels was achieved with weekly dosing at
      approximately 0.125 mg/kg, and a near-complete reduction in AT levels was
      achieved with weekly dosing at 1.5 mg/kg. Treatment with ALN-AT3 promoted
      hemostasis in mouse models of hemophilia and led to improved thrombin generation
      in an NHP model of hemophilia A with anti-factor VIII inhibitors. This
      investigational compound is currently in phase 1 clinical testing in subjects
      with hemophilia A or B. 

PMID- 25849133
TI  - Metformin activates a duodenal Ampk-dependent pathway to lower hepatic glucose
      production in rats.
AB  - Metformin is a first-line therapeutic option for the treatment of type 2
      diabetes, even though its underlying mechanisms of action are relatively unclear.
      Metformin lowers blood glucose levels by inhibiting hepatic glucose production
      (HGP), an effect originally postulated to be due to a hepatic AMP-activated
      protein kinase (AMPK)-dependent mechanism. However, studies have questioned the
      contribution of hepatic AMPK to the effects of metformin on lowering
      hyperglycemia, and a gut-brain-liver axis that mediates intestinal nutrient- and
      hormone-induced lowering of HGP has been identified. Thus, it is possible that
      metformin affects HGP through this inter-organ crosstalk. Here we show that
      intraduodenal infusion of metformin for 50 min activated duodenal mucosal Ampk
      and lowered HGP in a rat 3 d high fat diet (HFD)-induced model of insulin
      resistance. Inhibition of duodenal Ampk negated the HGP-lowering effect of
      intraduodenal metformin, and both duodenal glucagon-like peptide-1 receptor (Glp
      1r)-protein kinase A (Pka) signaling and a neuronal-mediated gut-brain-liver
      pathway were required for metformin to lower HGP. Preabsorptive metformin also
      lowered HGP in rat models of 28 d HFD-induced obesity and insulin resistance and
      nicotinamide (NA)-streptozotocin (STZ)-HFD-induced type 2 diabetes. In an
      unclamped setting, inhibition of duodenal Ampk reduced the glucose-lowering
      effects of a bolus metformin treatment in rat models of diabetes. These findings
      show that, in rat models of both obesity and diabetes, metformin activates a
      previously unappreciated duodenal Ampk-dependent pathway to lower HGP and plasma
      glucose levels. 

PMID- 25849134
TI  - Heparanase promotes tumor infiltration and antitumor activity of CAR-redirected T
      lymphocytes.
AB  - Adoptive transfer of chimeric antigen receptor (CAR)-redirected T lymphocytes
      (CAR-T cells) has had less striking therapeutic effects in solid tumors than in
      lymphoid malignancies. Although active tumor-mediated immunosuppression may have
      a role in limiting the efficacy of CAR-T cells, functional changes in T
      lymphocytes after their ex vivo manipulation may also account for the reduced
      ability of cultured CAR-T cells to penetrate stroma-rich solid tumors compared
      with lymphoid tissues. We therefore studied the capacity of human in vitro
      cultured CAR-T cells to degrade components of the extracellular matrix (ECM). In
      contrast to freshly isolated T lymphocytes, we found that in vitro-cultured T
      lymphocytes lack expression of the enzyme heparanase (HPSE), which degrades
      heparan sulfate proteoglycans, the main components of ECM. We found that HPSE
      mRNA is downregulated in in vitro-expanded T cells, which may be a consequence of
      p53 (officially known as TP53, encoding tumor protein 53) binding to the HPSE
      gene promoter. We therefore engineered CAR-T cells to express HPSE and showed
      their improved capacity to degrade the ECM, which promoted tumor T cell
      infiltration and antitumor activity. The use of this strategy may enhance the
      activity of CAR-T cells in individuals with stroma-rich solid tumors. 

PMID- 25849136
TI  - Interactions between Heterogeneous Uptake and Adsorption of Sulfur Dioxide and
      Acetaldehyde on Hematite.
AB  - Sulfur dioxide and organic aldehydes in the atmosphere are ubiquitous and often
      correlated with mineral dust aerosols. Heterogeneous uptake and adsorption of one
      of these species on mineral aerosols can potentially change the properties of the
      particles and further affect the subsequent heterogeneous reactions of the other
      species on the coating particles. In this study, the interactions between
      heterogeneous uptake and adsorption of sulfur dioxide and acetaldehyde on
      hematite are investigated by using in situ diffuse-reflectance infrared Fourier
      transform spectroscopy (DRIFTS) at room temperature. It is found that the
      preadsorption of SO2 on alpha-Fe2O3 can significantly hinder the subsequent
      heterogeneous oxidation of CH3CHO to acetate, while the preadsorption of CH3CHO
      significantly suppresses the heterogeneous reaction of large amounts of SO2 on
      the surface of alpha-Fe2O3 and has a little influence on the uptake of small
      amount of SO2. The heterogeneous reactions of SO2 on alpha-Fe2O3 preadsorbed by
      CH3CHO change the existing acetate on the particle surface into chemisorbed
      acetic acid, for the enhancement of surface acidity after the uptake of SO2.
      During these processes, different surface hydroxyl groups showed different
      reactivities. Atmospheric implications of this study are discussed. 

PMID- 25849137
TI  - Orbital Decompression for Compressive Optic Neuropathy in Patients with a
      Metastatic Orbital Tumor from Breast Carcinoma.
AB  - We report two patients who underwent orbital decompression for compressive optic
      neuropathy due to a metastatic orbital tumor from breast cancer. One patient was
      a 47-year-old woman with right compressive optic neuropathy. Balanced orbital
      decompression was performed 11 days after her first visit. At postoperative week
      1, her right visual acuity and critical flicker frequency value had improved from
      0.1 and 20 Hz to 1.0 and 35 Hz, respectively, and good vision was maintained at 6
      months postoperatively. The other patient was a 61-year-old woman with right
      compressive optic neuropathy. Medial orbital wall decompression was performed 5
      days after her first visit. Her right visual acuity and critical flicker
      frequency values improved until 38 days after the surgery, from 0.5 and 19 Hz to
      1.2 and 31 Hz, respectively, with stable good vision for the following 6 months. 

PMID- 25849135
TI  - Active Pin1 is a key target of all-trans retinoic acid in acute promyelocytic
      leukemia and breast cancer.
AB  - A common key regulator of oncogenic signaling pathways in multiple tumor types is
      the unique isomerase Pin1. However, available Pin1 inhibitors lack the required
      specificity and potency for inhibiting Pin1 function in vivo. By using mechanism
      based screening, here we find that all-trans retinoic acid (ATRA)--a therapy for
      acute promyelocytic leukemia (APL) that is considered the first example of
      targeted therapy in cancer, but whose drug target remains elusive--inhibits and
      degrades active Pin1 selectively in cancer cells by directly binding to the
      substrate phosphate- and proline-binding pockets in the Pin1 active site. ATRA
      induced Pin1 ablation degrades the protein encoded by the fusion oncogene PML
      RARA and treats APL in APL cell and animal models as well as in human patients.
      ATRA-induced Pin1 ablation also potently inhibits triple-negative breast cancer
      cell growth in human cells and in animal models by acting on many Pin1 substrate
      oncogenes and tumor suppressors. Thus, ATRA simultaneously blocks multiple Pin1
      regulated cancer-driving pathways, an attractive property for treating aggressive
      and drug-resistant tumors.

PMID- 25849139
TI  - Aspartic acid based nucleoside phosphoramidate prodrugs as potent inhibitors of
      hepatitis C virus replication.
AB  - In view of a persistent threat to mankind, the development of nucleotide-based
      prodrugs against hepatitis C virus (HCV) is considered as a constant effort in
      many medicinal chemistry groups. In an attempt to identify novel nucleoside
      phosphoramidate analogues for improving the anti-HCV activity, we have explored,
      for the first time, aspartic acid (Asp) and iminodiacetic acid (IDA) esters as
      amidate counterparts by considering three 2'-C-methyl containing nucleosides, 2'
      C-Me-cytidine, 2'-C-Me-uridine and 2'-C-Me-2'-fluoro-uridine. Synthesis of these
      analogues required protection for the vicinal diol functionality of the sugar
      moiety and the amino group of the cytidine nucleoside to regioselectively perform
      phosphorylation reaction at the 5'-hydroxyl group. Anti-HCV data demonstrate that
      the Asp-based phosphoramidates are ~550 fold more potent than the parent
      nucleosides. The inhibitory activity of the Asp-ProTides was higher than the Ala
      ProTides, suggesting that Asp would be a potential amino acid candidate to be
      considered for developing novel antiviral prodrugs. 

PMID- 25849140
TI  - Uniform sampling of steady states in metabolic networks: heterogeneous scales and
      rounding.
AB  - The uniform sampling of convex polytopes is an interesting computational problem
      with many applications in inference from linear constraints, but the performances
      of sampling algorithms can be affected by ill-conditioning. This is the case of
      inferring the feasible steady states in models of metabolic networks, since they
      can show heterogeneous time scales. In this work we focus on rounding procedures
      based on building an ellipsoid that closely matches the sampling space, that can
      be used to define an efficient hit-and-run (HR) Markov Chain Monte Carlo. In this
      way the uniformity of the sampling of the convex space of interest is rigorously
      guaranteed, at odds with non markovian methods. We analyze and compare three
      rounding methods in order to sample the feasible steady states of metabolic
      networks of three models of growing size up to genomic scale. The first is based
      on principal component analysis (PCA), the second on linear programming (LP) and
      finally we employ the Lovazs ellipsoid method (LEM). Our results show that a
      rounding procedure dramatically improves the performances of the HR in these
      inference problems and suggest that a combination of LEM or LP with a subsequent
      PCA perform the best. We finally compare the distributions of the HR with that of
      two heuristics based on the Artificially Centered hit-and-run (ACHR), gpSampler
      and optGpSampler. They show a good agreement with the results of the HR for the
      small network, while on genome scale models present inconsistencies. 

PMID- 25849138
TI  - Flavin-containing monooxygenase 3 as a potential player in diabetes-associated
      atherosclerosis.
AB  - Despite the well-documented association between insulin resistance and
      cardiovascular disease, the key targets of insulin relevant to the development of
      cardiovascular disease are not known. Here, using non-biased profiling methods,
      we identify the enzyme flavin-containing monooxygenase 3 (Fmo3) to be a target of
      insulin. FMO3 produces trimethylamine N-oxide (TMAO), which has recently been
      suggested to promote atherosclerosis in mice and humans. We show that FMO3 is
      suppressed by insulin in vitro, increased in obese/insulin resistant male mice
      and increased in obese/insulin-resistant humans. Knockdown of FMO3 in insulin
      resistant mice suppresses FoxO1, a central node for metabolic control, and
      entirely prevents the development of hyperglycaemia, hyperlipidemia and
      atherosclerosis. Taken together, these data indicate that FMO3 is required for
      FoxO1 expression and the development of metabolic dysfunction. 

PMID- 25849141
TI  - CDK9 inhibitors define elongation checkpoints at both ends of RNA polymerase II
      transcribed genes.
AB  - Transcription through early-elongation checkpoints requires phosphorylation of
      negative transcription elongation factors (NTEFs) by the cyclin-dependent kinase
      (CDK) 9. Using CDK9 inhibitors and global run-on sequencing (GRO-seq), we have
      mapped CDK9 inhibitor-sensitive checkpoints genome wide in human cells. Our data
      indicate that early-elongation checkpoints are a general feature of RNA
      polymerase (pol) II-transcribed human genes and occur independently of polymerase
      stalling. Pol II that has negotiated the early-elongation checkpoint can elongate
      in the presence of inhibitors but, remarkably, terminates transcription
      prematurely close to the terminal polyadenylation (poly(A)) site. Our analysis
      has revealed an unexpected poly(A)-associated elongation checkpoint, which has
      major implications for the regulation of gene expression. Interestingly, the
      pattern of modification of the C-terminal domain of pol II terminated at this new
      checkpoint largely mirrors the pattern normally found downstream of the poly(A)
      site, thus suggesting common mechanisms of termination. 

PMID- 25849142
TI  - Crystal structure of a light-driven sodium pump.
AB  - Recently, the first known light-driven sodium pumps, from the microbial rhodopsin
      family, were discovered. We have solved the structure of one of them,
      Krokinobacter eikastus rhodopsin 2 (KR2), in the monomeric blue state and in two
      pentameric red states, at resolutions of 1.45 A and 2.2 and 2.8 A, respectively.
      The structures reveal the ion-translocation pathway and show that the sodium ion
      is bound outside the protein at the oligomerization interface, that the ion
      release cavity is capped by a unique N-terminal alpha-helix and that the ion
      uptake cavity is unexpectedly large and open to the surface. Obstruction of the
      cavity with the mutation G263F imparts KR2 with the ability to pump potassium.
      These results pave the way for the understanding and rational design of cation
      pumps with new specific properties valuable for optogenetics. 

PMID- 25849143
TI  - Structural mechanism of integrin inactivation by filamin.
AB  - Activation of heterodimeric (alphabeta) integrin is crucial for regulating cell
      adhesion. Binding of talin to the cytoplasmic face of integrin activates the
      receptor, but how integrin is maintained in a resting state to counterbalance its
      activation has remained obscure. Here, we report the structure of the cytoplasmic
      domain of human integrin alphaIIbbeta3 bound to its inhibitor, the immunoglobin
      repeat 21 of filamin A (FLNa-Ig21). The structure reveals an unexpected ternary
      complex in which FLNa-Ig21 not only binds to the C terminus of the integrin beta3
      cytoplasmic tail (CT), as previously predicted, but also engages N-terminal
      helices of alphaIIb and beta3 CTs to stabilize an inter-CT clasp that helps
      restrain the integrin in a resting state. Combined with functional data, the
      structure reveals a new mechanism of filamin-mediated retention of inactive
      integrin, suggesting a new framework for understanding regulation of integrin
      activation and adhesion. 

PMID- 25849144
TI  - A lncRNA regulates alternative splicing via establishment of a splicing-specific
      chromatin signature.
AB  - Alternative pre-mRNA splicing is a highly cell type-specific process essential to
      generating protein diversity. However, the mechanisms responsible for the
      establishment and maintenance of heritable cell-specific alternative-splicing
      programs are poorly understood. Recent observations point to a role of histone
      modifications in the regulation of alternative splicing. Here we report a new
      mechanism of chromatin-mediated splicing control involving a long noncoding RNA
      (lncRNA). We have identified an evolutionarily conserved nuclear antisense
      lncRNA, generated from within the human FGFR2 locus, that promotes epithelial
      specific alternative splicing of FGFR2. The lncRNA acts through recruitment of
      Polycomb-group proteins and the histone demethylase KDM2a to create a chromatin
      environment that impairs binding of a repressive chromatin-splicing adaptor
      complex important for mesenchymal-specific splicing. Our results uncover a new
      function for lncRNAs in the establishment and maintenance of cell-specific
      alternative splicing via modulation of chromatin signatures. 

PMID- 25849145
TI  - Induction of size-dependent breakdown of blood-milk barrier in lactating mice by
      TiO2 nanoparticles.
AB  - This study aims to investigate the potential nanotoxic effects of TiO2
      nanoparticles (TNPs) to dams and pups during lactation period. TiO2 nanoparticles
      are accumulated in mammary glands of lactating mice after i.v. administration.
      This accumulation of TiO2 NP likely causes a ROS-induced disruption of tight
      junction of the blood-milk barrier as indicated by the loss of tight junction
      proteins and the shedding of alveolar epithelial cells. Compared to larger TNPs
      (50 nm), smaller ones (8 nm) exhibit a higher accumulation in mammary glands and
      are more potent in causing perturbations to blood-milk barrier. An alarming
      finding is that the smaller TNPs (8 nm) are transferred from dams to pups through
      breastfeeding, likely through the disrupted blood-milk barrier. However, during
      the lactation period, the nutrient quality of milk from dams and the early
      developmental landmarks of the pups are not affected by above perturbations. 

PMID- 25849146
TI  - Spatiotemporal evolution of Calophaca (fabaceae) reveals multiple dispersals in
      central Asian mountains.
AB  - BACKGROUND: The Central Asian flora plays a significant role in Eurasia and the
      Northern Hemisphere. Calophaca, a member of this flora, includes eight currently
      recognized species, and is centered in Central Asia, with some taxa extending
      into adjacent areas. A phylogenetic analysis of the genus utilizing nuclear
      ribosomal ITS and plastid trnS-trnG and rbcL sequences was carried out in order
      to confirm its taxonomic status and reconstruct its evolutionary history.
      METHODOLOGY/PRINCIPAL FINDING: We employed BEAST Bayesian inference for dating,
      and S-DIVA and BBM for ancestral area reconstruction, to study its spatiotemporal
      evolution. Our results show that Calophacais monophyletic and nested within
      Caragana. The divergence time of Calophaca is estimated at ca. 8.0 Ma, most
      likely driven by global cooling and aridification, influenced by rapid uplift of
      the Qinghai Tibet Plateau margins. CONCLUSIONS/SIGNIFICANCE: According to
      ancestral area reconstructions, the genus most likely originated in the Pamir
      Mountains, a global biodiversity hotspot and hypothesized Tertiary refugium of
      many Central Asian plant lineages. Dispersals from this location are inferred to
      the western Tianshan Mountains, then northward to the Tarbagatai Range, eastward
      to East Asia, and westward to the Caucasus, Russia, and Europe. The
      spatiotemporal evolution of Calophaca provides a case contributing to an
      understanding of the flora and biodiversity of the Central Asian mountains and
      adjacent regions.

PMID- 25849147
TI  - Anatomical Authorities: On the Epistemological Exclusion of Trans-Surgical
      Patients.
AB  - American feminist health activists in the 1970s created representations of
      genital anatomy intended to replace the abstracted images of biomedicine's
      'modest witness,' with what Michelle Murphy has called the 'immodest witness,'
      authority explicitly derived from personal and embodied experience. Decades
      later, a feminist publication in the tradition of the immodest witness called
      Femalia was adopted into the practice of an American surgeon specializing in
      trans- genital sex reassignment surgery (GSRS). Based on ethnographic and textual
      research, I show how oppositional claims to represent the 'natural' female body
      one valued for its medical objectivity and the other for its feminist
      subjectivity-effectively foreclosed these as modes of authority through which the
      trans- patient might contribute to her surgical care. I argue that trans-
      patients' double epistemological exclusion contributes to a broader asymmetry in
      the use of patients' subjective reports in the everyday practice of GSRS and the
      clinical research by which it is evaluated. 

PMID- 25849148
TI  - Probing the cis-arrangement of prototype tight junction proteins claudin-1 and
      claudin-3.
AB  - Claudins form a large family of TJ (tight junction) proteins featuring four
      transmembrane segments (TM1-TM4), two extracellular loops, one intracellular loop
      and intracellular N- and C-termini. They form continuous and branched TJ strands
      by homo- or heterophilic interaction within the same membrane (cis-interaction)
      and with claudins of the opposing lateral cell membrane (trans-interaction). In
      order to clarify the molecular organization of TJ strand formation, we
      investigated the cis-interaction of two abundant prototypic claudins. Human
      claudin-1 and claudin-3, fused to ECFP or EYFP at the N- or C-terminus, were
      expressed in the TJ-free cell line HEK (human embryonic kidney)-293. Using FRET
      analysis, the proximity of claudin N- and C-termini integrated in homopolymeric
      strands composed of claudin-3 or of heteropolymeric strands composed of claudin-1
      and claudin-3 were determined. The main results are that (i) within homo- and
      heteropolymers, the average distance between the cytoplasmic ends of the TM1s of
      cis-interacting claudin molecules is shorter than the average distance between
      their TM4s, and (ii) TM1 segments of neighbouring claudins are oriented towards
      each other as the cytoplasmic end of TM1 is in close proximity to more other TM1
      segments than TM4 is to other TM4 segments. The results indicate at least two
      different cis-interaction interfaces within claudin-3 homopolymers as well as
      within claudin-1/claudin-3 heteropolymers. The data provide novel insight into
      the molecular TJ architecture consistent with a model with an antiparallel double
      row cis-arrangement of classic claudin protomers within strands. 

PMID- 25849149
TI  - Fitness of Leishmania donovani parasites resistant to drug combinations.
AB  - Drug resistance represents one of the main problems for the use of chemotherapy
      to treat leishmaniasis. Additionally, it could provide some advantages to
      Leishmania parasites, such as a higher capacity to survive in stress conditions.
      In this work, in mixed populations of Leishmania donovani parasites, we have
      analyzed whether experimentally resistant lines to one or two combined anti
      leishmanial drugs better support the stress conditions than a susceptible line
      expressing luciferase (Luc line). In the absence of stress, none of the
      Leishmania lines showed growth advantage relative to the other when mixed at a
      1:1 parasite ratio. However, when promastigotes from resistant lines and the Luc
      line were mixed and exposed to different stresses, we observed that the resistant
      lines are more tolerant of different stress conditions: nutrient starvation and
      heat shock-pH stress. Further to this, we observed that intracellular amastigotes
      from resistant lines present a higher capacity to survive inside the macrophages
      than those of the control line. These results suggest that resistant parasites
      acquire an overall fitness increase and that resistance to drug combinations
      presents significant differences in their fitness capacity versus single-drug
      resistant parasites, particularly in intracellular amastigotes. These results
      contribute to the assessment of the possible impact of drug resistance on
      leishmaniasis control programs. 

PMID- 25849150
TI  - Rank diversity of languages: generic behavior in computational linguistics.
AB  - Statistical studies of languages have focused on the rank-frequency distribution
      of words. Instead, we introduce here a measure of how word ranks change in time
      and call this distribution rank diversity. We calculate this diversity for books
      published in six European languages since 1800, and find that it follows a
      universal lognormal distribution. Based on the mean and standard deviation
      associated with the lognormal distribution, we define three different word
      regimes of languages: "heads" consist of words which almost do not change their
      rank in time, "bodies" are words of general use, while "tails" are comprised by
      context-specific words and vary their rank considerably in time. The heads and
      bodies reflect the size of language cores identified by linguists for basic
      communication. We propose a Gaussian random walk model which reproduces the rank
      variation of words in time and thus the diversity. Rank diversity of words can be
      understood as the result of random variations in rank, where the size of the
      variation depends on the rank itself. We find that the core size is similar for
      all languages studied. 

PMID- 25849151
TI  - Negotiating agency in cases of intimate partner violence in Vietnam.
AB  - Understandings of women's agency in cases of intimate partner violence (IPV) have
      been dominated by an individualistic focus on help-seeking behaviour. The role of
      children in influencing, enabling and restricting the decision-making processes
      of their mothers has been largely ignored. We adopt biographical analytical
      approaches to qualitative longitudinal data collected as part of the Young Lives
      study to highlight the interdependency of women's and children's agency in
      contexts of IPV in Vietnam. We illustrate how women's agency is both enabled and
      constrained by their relationships with their children, as well as by wider
      structural processes, and examine how gender and generation intersect. In
      marginalised settings where few formal services exist or strong social norms
      preclude women from accessing support, understanding these informal coping
      strategies and the processes by which these are negotiated is essential for
      developing more effective policy responses. 

PMID- 25849152
TI  - Footprints of middle ages kingdoms are still visible in the contemporary surname
      structure of Spain.
AB  - To assess whether the present-day geographical variability of Spanish surnames
      mirrors historical phenomena occurred at the times of their introduction (13th
      16th century), and to infer the possible effect of foreign immigration (about 11%
      of present-day) on the observed patterns of diversity, we have analyzed the
      frequency distribution of 33,753 unique surnames (tokens) occurring 51,419,788
      times, according to the list of Spanish residents of the year 2008. Isonymy
      measures and surname distances have been computed for, and between, the 47
      mainland Spanish provinces and compared to a numerical classification of
      corresponding language varieties spoken in Spain. The comparison of the two
      bootstrap consensus trees, representing surname and linguistic variability,
      suggests a similar picture; major clusters are located in the east (Aragon,
      Cataluna, Valencia), and in the north of the country (Asturias, Galicia, Leon).
      Remaining regions appear to be considerably homogeneous. We interpret this
      pattern as the long-lasting effect of the surname and linguistic normalization
      actively led by the Christian kingdoms of the north (Reigns of Castilla y Leon
      and Aragon) during and after the southwards reconquest (Reconquista) of the
      territories ruled by the Arabs from the 8th century to the late 15th century,
      that is when surnames became transmitted in a fixed way and when Castilian
      linguistic varieties became increasingly prestigious and spread out. The
      geography of contemporary surname and linguistic variability in Spain corresponds
      to the political geography at the end of the Middle-Ages. The synchronicity
      between surname adoption and the political and cultural effects of the
      Reconquista have permanently forged a Spanish identity that subsequent
      migrations, internal or external, did not deface. 

PMID- 25849153
TI  - Towards unraveling the human tooth transcriptome: the dentome.
AB  - The goal of the study was to characterize the transcriptome profiles of human
      ameloblasts and odontoblasts, evaluate molecular pathways and advance our
      knowledge of the human "dentome". Laser capture microdissection was used to
      isolate odontoblasts and ameloblasts from human tooth buds (15-20week gestational
      age) from 4 fetuses. RNA was examined using Agilent 41k whole genome arrays at 2
      different stages of enamel formation, presecretory and secretory. Probe detection
      was considered against the array negative control to control for background
      noise. Differential expression was examined using Significance Analysis of
      Microarrays (SAM) 4.0 between different cell types and developmental stages with
      a false discovery rate of 20%. Pathway analysis was conducted using Ingenuity
      Pathway Analysis software. We found that during primary tooth formation,
      odontoblasts expressed 14,802 genes, presecretory ameloblasts 15,179 genes and
      secretory ameloblasts 14,526 genes. Genes known to be active during tooth
      development for each cell type (eg COL1A1, AMELX) were shown to be expressed by
      our approach. Exploring further into the list of differentially expressed genes
      between the motile odontoblasts and non-motile presecretory ameloblasts we found
      several genes of interest that could be involved in cell movement (FN1, LUM,
      ASTN1). Furthermore, our analysis indicated that the Phospholipase C and ERK5
      pathways, that are important for cell movement, were activated in the motile
      odontoblasts. In addition our pathway analysis identified WNT3A and TGFB1 as
      important upstream contributors. Recent studies implicate these genes in the
      development of Schimke immuno-osseous dysplasia. The utility of laser capture
      microdissection can be a valuable tool in the examination of specific tissues or
      cell populations present in human tooth buds. Advancing our knowledge of the
      human dentome and related molecular pathways provides new insights into the
      complex mechanisms regulating odontogenesis and biomineralization. This knowledge
      could prove useful in future studies of odontogenic related pathologies. 

PMID- 25849154
TI  - Enantioselective Arylative Dearomatization of Indoles via Pd-Catalyzed
      Intramolecular Reductive Heck Reactions.
AB  - A highly enantioselective intramolecular arylative dearomatization of indoles via
      palladium-catalyzed reductive Heck reactions was developed. The new strategy led
      to a series of optically active indolines bearing C2-quaternary stereocenters in
      modest to good yields with excellent enantioselectivities (up to 99% ee). 

PMID- 25849156
TI  - A Comparison of the Perceptual and Technical Demands of Tennis Training,
      Simulated Match Play, and Competitive Tournaments.
AB  - PURPOSE: High-performance tennis environments aim to prepare athletes for
      competitive demands through simulated-match scenarios and drills. With a dearth
      of direct comparisons between training and tournament demands, the current
      investigation compared the perceptual and technical characteristics of training
      drills, simulated match play, and tournament matches. METHODS: Data were
      collected from 18 high-performance junior tennis players (gender: 10 male, 8
      female; age 16 +/- 1.1 y) during 6 +/- 2 drill-based training sessions, 5 +/- 2
      simulated match-play sessions, and 5 +/- 3 tournament matches from each
      participant. Tournament matches were further distinguished by win or loss and
      against seeded or nonseeded opponents. Notational analysis of stroke and error
      rates, winners, and serves, along with rating of perceived physical exertion
      (RPE) and mental exertion was measured postsession. RESULTS: Repeated-measures
      analyses of variance and effect-size analysis revealed that training sessions
      were significantly shorter in duration than tournament matches (P < .05, d =
      1.18). RPEs during training and simulated match-play sessions were lower than in
      tournaments (P > .05; d = 1.26, d = 1.05, respectively). Mental exertion in
      training was lower than in both simulated match play and tournaments (P > .05; d
      = 1.10, d = 0.86, respectively). Stroke rates during tournaments exceeded those
      observed in training (P < .05, d = 3.41) and simulated-match-play (P < .05, d =
      1.22) sessions. Furthermore, the serve was used more during tournaments than
      simulated match play (P < .05, d = 4.28), while errors and winners were similar
      independent of setting (P > .05, d < 0.80). CONCLUSIONS: Training in the form of
      drills or simulated match play appeared to inadequately replicate tournament
      demands in this cohort of players. Coaches should be mindful of match demands to
      best prescribe sessions of relevant duration, as well as internal (RPE) and
      technical (stroke rate) load, to aid tournament preparation.

PMID- 25849155
TI  - Histone chaperones in Arabidopsis and rice: genome-wide identification,
      phylogeny, architecture and transcriptional regulation.
AB  - BACKGROUND: Histone chaperones modulate chromatin architecture and hence play a
      pivotal role in epigenetic regulation of gene expression. In contrast to their
      animal and yeast counterparts, not much is known about plant histone chaperones.
      To gain insights into their functions in plants, we sought to identify histone
      chaperones from two model plant species and investigated their phylogeny, domain
      architecture and transcriptional profiles to establish correlation between their
      expression patterns and potential role in stress physiology and plant
      development. RESULTS: Through comprehensive whole genome analyses of Arabidopsis
      and rice, we identified twenty-two and twenty-five genes encoding histone
      chaperones in these plants, respectively. These could be classified into seven
      different families, namely NAP, CAF1, SPT6, ASF1, HIRA, NASP, and FACT.
      Phylogenetic analyses of histone chaperones from diverse organisms including
      representative species from each of the major plant groups, yeast and human
      indicated functional divergence in NAP and CAF1C in plants. For the largest
      histone chaperone family, NAP, phylogenetic reconstruction suggested the presence
      of two distinct groups in plants, possibly with differing histone preferences.
      Further, to comment upon their physiological roles in plants, we analyzed their
      expression at different developmental stages, across various plant tissues, and
      under biotic and abiotic stress conditions using pre-existing microarray and qRT
      PCR. We found tight transcriptional regulation of some histone chaperone genes
      during development in both Arabidopsis and rice, suggesting that they may play a
      role in genetic reprogramming associated with the developmental process. Besides,
      we found significant differential expression of a few histone chaperones under
      various biotic and abiotic stresses pointing towards their potential function in
      stress response. CONCLUSIONS: Taken together, our findings shed light onto the
      possible evolutionary trajectory of plant histone chaperones and present novel
      prospects about their physiological roles. Considering that the developmental
      process and stress response require altered expression of a large array of genes,
      our results suggest that some plant histone chaperones may serve a regulatory
      role by controlling the expression of genes associated with these vital
      processes, possibly via modulating chromatin dynamics at the corresponding
      genetic loci.

PMID- 25849158
TI  - Alternatives to conventional thermal treatments in fruit-juice processing. Part
      1: Techniques and applications.
AB  - This paper provides an overview of alternatives to conventional thermal
      treatments and a review of the literature on fruit-juice processing for three key
      operations in fruit-juice production such as microbial inactivation, enzyme
      inactivation, and juice yield enhancement, these being radiation treatments (UV
      light, high-intensity light pulses, gamma-irradiation), electrical treatments
      (pulsed electric fields, radiofrequency electric fields, ohmic heating),
      microwave heating, ultrasound, high hydrostatic pressure, inert gas treatments
      (supercritical carbon dioxide, ozonation), and flash-vacuum expansion. The
      nonthermal technologies discussed in this review have the potential to meet
      industry and consumer expectations. However, the lack of standardization in
      operating conditions hampers comparisons among different studies, and
      consequently ambiguity arises within the literature. For the juice industry to
      advance, more detailed studies are needed on the scaling-up, process design, and
      optimization, as well as on the effect of such technologies on juice quality of
      juices in order to maximize their potential as alternative nonthermal
      technologies in fruit-juice processing.

PMID- 25849157
TI  - Enhanced endogenous bone morphogenetic protein signaling protects against
      bleomycin induced pulmonary fibrosis.
AB  - BACKGROUND: Effective treatments for fibrotic diseases such as idiopathic
      pulmonary fibrosis are largely lacking. Transforming growth factor beta (TGFbeta)
      plays a central role in the pathophysiology of fibrosis. We hypothesized that
      bone morphogenetic proteins (BMP), another family within the TGFbeta superfamily
      of growth factors, modulate fibrogenesis driven by TGFbeta. We therefore studied
      the role of endogenous BMP signaling in bleomycin induced lung fibrosis. METHODS:
      Lung fibrosis was induced in wild-type or noggin haploinsufficient (Nog +/LacZ )
      mice by intratracheal instillation of bleomycin, or phosphate buffered saline as
      a control. Invasive pulmonary function tests were performed using the
      flexiVent(r) SCIREQ system. The mice were sacrificed and lung tissue was
      collected for analysis using histopathology, collagen quantification,
      immunohistochemistry and gene expression analysis. RESULTS: Nog +/LacZ mice are a
      known model of increased BMP signaling and were partially protected from
      bleomycin-induced lung fibrosis with reduced Ashcroft score, reduced collagen
      content and preservation of pulmonary compliance. In bleomycin-induced lung
      fibrosis, TGFbeta and BMP signaling followed an inverse course, with dynamic
      activation of TGFbeta signaling and repression of BMP signaling activity.
      CONCLUSIONS: Upon bleomycin exposure, active BMP signaling is decreased.
      Derepression of BMP signaling in Nog +/LacZ mice protects against bleomycin
      induced pulmonary fibrosis. Modulating the balance between BMP and TGFbeta, in
      particular increasing endogenous BMP signals, may therefore be a therapeutic
      target in fibrotic lung disease.

PMID- 25849160
TI  - Erbium hydroxide ethanedisulfonate: a cationic layered material with organic
      anion exchange capability.
AB  - We describe a cationic erbium-based material
      [Er12(OH)29(H2O)5][O3SCH2CH2SO3]3.5.5H2O. As synthesized, the material is water
      stable and capable of complete organic anion exchange for a variety of
      alpha,omega-alkanedicarboxylates. We chose these anions as initial examples of
      exchange and as an analog for pharmaceutical waste, some of which have a
      carboxylate functionality at neutral pH range. Free-floating and partially
      anchored organosulfonate anions reside between the cationic corrugated layers and
      allow for exchange. The structure also displays a reversible hydration event
      above 100  degrees C. Both the as-synthesized and the exchanged materials are
      characterized by a variety of analytical techniques. 

PMID- 25849159
TI  - Psychological predictors of recovery from low back pain: a prospective study.
AB  - BACKGROUND: Recovery from low back pain (LBP) is an important outcome for
      patients and clinicians. Psychological factors are known to impact the course of
      LBP but have not been extensively investigated for predicting recovery. The
      purposes of this study were to: 1) describe LBP recovery rates at 6 months
      following 4 weeks of physical therapy; 2) identify psychological factors
      predictive of 6 month recovery status; and 3) identify psychological factors that
      co-occur with 6 month recovery status. METHODS: This study was a secondary
      analysis of a prospective cohort of patients (n = 111) receiving outpatient
      physical therapy for LBP. Patients were administered the STarT Back Screening
      Tool (SBT), individual psychological measures, a numerical pain rating scale
      (NPRS) and Roland Morris Disability Questionnaire (RMDQ) at intake, 4-week, and 6
      month assessments. LBP recovery was operationally defined based on meeting NPRS =
      0/10 and RMDQ <= 2 criterion at 6-month follow-up assessment. Recovery groups
      were then compared for differences on all variables at intake and on individual
      psychological measures at 6-months. Discriminant function analysis (DFA)
      identified which descriptive variables were predictive of recovery status.
      RESULTS: The 6-month recovery rate was 14/111 (12.6%) for the combined NPRS and
      RMDQ criterion. Non-recovered patients were associated with SBT risk status (p =
      0.004), higher intake pain intensity (p = .008) and higher depressive symptoms (p
      < .001) scores compared to recovered patients. The overall accuracy for intake
      classification using DFA was 87.2% with SBT risk status, pain intensity, and
      depressive symptoms all making unique contributions. At 6-months, non-recovered
      patients had higher fear-avoidance, kinesiophobia, and depressive symptoms (p's <
      .001) compared to recovered patients. The overall accuracy for 6-month
      classification using DFA was 86.4% with fear-avoidance, kinesiophobia, and
      depressive symptoms all making unique contributions. CONCLUSIONS: Our findings
      indicated that psychological risk status, depressive symptoms, and pain intensity
      were predictive of 6 month recovery status. Furthermore elevated fear-avoidance,
      kinesiophobia, and depressive symptoms co-occurred with non-recovery at 6 months.
      Future studies should investigate whether stratified psychologically informed
      treatment options have the potential to improve recovery rates for those most at
      risk for non-recovery.

PMID- 25849161
TI  - In vitro antioxidant capacity and free radical scavenging evaluation of active
      metabolite constituents of Newbouldia laevis ethanolic leaf extract.
AB  - BACKGROUND: The aim of the present study was to evaluate the in vitro antioxidant
      and free radical scavenging capacity of bioactive metabolites present in
      Newbouldia laevis leaf extract. RESULTS: Chromatographic and spectrophotometric
      methods were used in the study and modified where necessary in the study.
      Bioactivity of the extract was determined at 10 MUg/ml, 50 MUg/ml, 100 MUg/ml,
      200 MUg/ml and 400 MUg/ml concentrations expressed in % inhibition. The yield of
      the ethanolic leaf extract of N.laevis was 30.3 g (9.93%). Evaluation of
      bioactive metabolic constituents gave high levels of ascorbic acid (515.53 +/- 12
      IU/100 g [25.7 mg/100 g]), vitamin E (26.46 +/- 1.08 IU/100 g), saponins (6.2 +/-
      0.10), alkaloids (2.20 +/- 0.03), cardiac glycosides(1.48 +/- 0.22), amino acids
      and steroids (8.01 +/- 0.04) measured in mg/100 g dry weight; moderate levels of
      vitamin A (188.28 +/- 6.19 IU/100 g), tannins (0.09 +/- 0.30), terpenoids (3.42
      +/- 0.67); low level of flavonoids (1.01 +/- 0.34 mg/100 g) and absence of
      cyanogenic glycosides, carboxylic acids and aldehydes/ketones. The extracts
      percentage inhibition of DPPH, hydroxyl radical (OH.), superoxide anion (O2 .-),
      iron chelating, nitric oxide radical (NO), peroxynitrite (ONOO-), singlet oxygen
      (1O2), hypochlorous acid (HOCl), lipid peroxidation (LPO) and FRAP showed a
      concentration-dependent antioxidant activity with no significant difference with
      the controls. Though, IC50 of the extract showed significant difference only in
      singlet oxygen (1O2) and iron chelating activity when compared with the controls.
      CONCLUSIONS: The extract is a potential source of antioxidants/free radical
      scavengers having important metabolites which maybe linked to its ethno-medicinal
      use.

PMID- 25849163
TI  - Accurate Composite and Fragment-Based Quantum Chemical Models for Large
      Molecules.

PMID- 25849166
TI  - Abstraction: windows: Jeanne Rij-Rousseau.

PMID- 25849162
TI  - The E3 ligase OsPUB15 interacts with the receptor-like kinase PID2 and regulates
      plant cell death and innate immunity.
AB  - BACKGROUND: Rice blast disease is one of the most destructive diseases of rice
      worldwide. We previously cloned the rice blast resistance gene Pid2, which
      encodes a transmembrane receptor-like kinase containing an extracellular B-lectin
      domain and an intracellular serine/threonine kinase domain. However, little is
      known about Pid2-mediated signaling. RESULTS: Here we report the functional
      characterization of the U-box/ARM repeat protein OsPUB15 as one of the PID2
      binding proteins. We found that OsPUB15 physically interacted with the kinase
      domain of PID2 (PID2K) in vitro and in vivo and the ARM repeat domain of OsPUB15
      was essential for the interaction. In vitro biochemical assays indicated that
      PID2K possessed kinase activity and was able to phosphorylate OsPUB15. We also
      found that the phosphorylated form of OsPUB15 possessed E3 ligase activity.
      Expression pattern analyses revealed that OsPUB15 was constitutively expressed
      and its encoded protein OsPUB15 was localized in cytosol. Transgenic rice plants
      over-expressing OsPUB15 at early stage displayed cell death lesions spontaneously
      in association with a constitutive activation of plant basal defense responses,
      including excessive accumulation of hydrogen peroxide, up-regulated expression of
      pathogenesis-related genes and enhanced resistance to blast strains. We also
      observed that, along with plant growth, the cell death lesions kept spreading
      over the whole seedlings quickly resulting in a seedling lethal phenotype.
      CONCLUSIONS: These results reveal that the E3 ligase OsPUB15 interacts directly
      with the receptor-like kinase PID2 and regulates plant cell death and blast
      disease resistance.

PMID- 25849167
TI  - Exome sequencing comes to the clinic.

PMID- 25849168
TI  - How useful are screening tests?

PMID- 25849178
TI  - A piece of my mind. The other generation.

PMID- 25849177
TI  - Hospital credentialing and privileging of surgeons: a potential safety blind
      spot.

PMID- 25849180
TI  - Multiple blood pressure medications and mortality among elderly individuals.

PMID- 25849181
TI  - Association between perioperative low-molecular-weight heparin vs unfractionated
      heparin and clinical outcomes in patients with cancer undergoing surgery.
AB  - CLINICAL QUESTION: In patients with cancer undergoing surgery, what is the
      association between perioperative thromboprophylaxis with low-molecular-weight
      heparin (LMWH) or unfractionated heparin and mortality, pulmonary embolism, deep
      venous thrombosis, thrombocytopenia, and bleeding outcomes? BOTTOM LINE: When
      used for perioperative thromboprophylaxis, there are no differences in the
      association of LMWH vs unfractionated heparin for preventing mortality, pulmonary
      embolism, deep venous thrombosis, bleeding outcomes, or thrombocytopenia in
      patients with cancer.

PMID- 25849182
TI  - Painful rash in a patient with bronchiectasis.

PMID- 25849183
TI  - Patients with next-of-kin relationships outside the nuclear family.

PMID- 25849184
TI  - Hypofractionated whole breast irradiation for early-stage breast cancer.

PMID- 25849185
TI  - Low vs high glycemic index diet.

PMID- 25849186
TI  - Hypofractionated whole breast irradiation for early-stage breast cancer--reply.

PMID- 25849187
TI  - Low vs high glycemic index diet--reply.

PMID- 25849188
TI  - Electronic health records and adolescent privacy.

PMID- 25849189
TI  - Electronic health records and adolescent privacy--reply.

PMID- 25849190
TI  - Incorrect absolute risk values.

PMID- 25849191
TI  - Misspelled author name.

PMID- 25849192
TI  - Incorrect author affiliation.

PMID- 25849179
TI  - Association of type and location of BRCA1 and BRCA2 mutations with risk of breast
      and ovarian cancer.
AB  - IMPORTANCE: Limited information about the relationship between specific mutations
      in BRCA1 or BRCA2 (BRCA1/2) and cancer risk exists. OBJECTIVE: To identify
      mutation-specific cancer risks for carriers of BRCA1/2. DESIGN, SETTING, AND
      PARTICIPANTS: Observational study of women who were ascertained between 1937 and
      2011 (median, 1999) and found to carry disease-associated BRCA1 or BRCA2
      mutations. The international sample comprised 19,581 carriers of BRCA1 mutations
      and 11,900 carriers of BRCA2 mutations from 55 centers in 33 countries on 6
      continents. We estimated hazard ratios for breast and ovarian cancer based on
      mutation type, function, and nucleotide position. We also estimated RHR, the
      ratio of breast vs ovarian cancer hazard ratios. A value of RHR greater than 1
      indicated elevated breast cancer risk; a value of RHR less than 1 indicated
      elevated ovarian cancer risk. EXPOSURES: Mutations of BRCA1 or BRCA2. MAIN
      OUTCOMES AND MEASURES: Breast and ovarian cancer risks. RESULTS: Among BRCA1
      mutation carriers, 9052 women (46%) were diagnosed with breast cancer, 2317 (12%)
      with ovarian cancer, 1041 (5%) with breast and ovarian cancer, and 7171 (37%)
      without cancer. Among BRCA2 mutation carriers, 6180 women (52%) were diagnosed
      with breast cancer, 682 (6%) with ovarian cancer, 272 (2%) with breast and
      ovarian cancer, and 4766 (40%) without cancer. In BRCA1, we identified 3 breast
      cancer cluster regions (BCCRs) located at c.179 to c.505 (BCCR1; RHR = 1.46; 95%
      CI, 1.22-1.74; P = 2 * 10(-6)), c.4328 to c.4945 (BCCR2; RHR = 1.34; 95% CI, 1.01
      1.78; P = .04), and c. 5261 to c.5563 (BCCR2', RHR = 1.38; 95% CI, 1.22-1.55; P =
      6 * 10(-9)). We also identified an ovarian cancer cluster region (OCCR) from
      c.1380 to c.4062 (approximately exon 11) with RHR = 0.62 (95% CI, 0.56-0.70; P =
      9 * 10(-17)). In BRCA2, we observed multiple BCCRs spanning c.1 to c.596 (BCCR1;
      RHR = 1.71; 95% CI, 1.06-2.78; P = .03), c.772 to c.1806 (BCCR1'; RHR = 1.63; 95%
      CI, 1.10-2.40; P = .01), and c.7394 to c.8904 (BCCR2; RHR = 2.31; 95% CI, 1.69
      3.16; P = .00002). We also identified 3 OCCRs: the first (OCCR1) spanned c.3249
      to c.5681 that was adjacent to c.5946delT (6174delT; RHR = 0.51; 95% CI, 0.44
      0.60; P = 6 * 10(-17)). The second OCCR spanned c.6645 to c.7471 (OCCR2; RHR =
      0.57; 95% CI, 0.41-0.80; P = .001). Mutations conferring nonsense-mediated decay
      were associated with differential breast or ovarian cancer risks and an earlier
      age of breast cancer diagnosis for both BRCA1 and BRCA2 mutation carriers.
      CONCLUSIONS AND RELEVANCE: Breast and ovarian cancer risks varied by type and
      location of BRCA1/2 mutations. With appropriate validation, these data may have
      implications for risk assessment and cancer prevention decision making for
      carriers of BRCA1 and BRCA2 mutations.

PMID- 25849194
TI  - The care of the baby's eyes in the perambulator.

PMID- 25849196
TI  - Mitochondrial tRNA-lookalikes in nuclear chromosomes: could they be functional?
AB  - The presence in human nuclear chromosomes of multiple sequences that are highly
      similar to human mitochondrial tRNAs (tRNA-lookalikes) raises intriguing
      questions about the possible functionality of these genomic loci. In this
      perspective, we explore the significance of the mitochondrial tRNA-lookalikes
      based on a series of properties that argue for their non-accidental nature. We
      particularly focus on the possibility of transcription as well as on potential
      functional roles for these sequences that can range from their acting as DNA
      regulatory elements to forming functional mature tRNAs or tRNA-derived fragments.
      Extension of our analysis to other simians (chimp, gorilla, rhesus, and squirrel
      monkey), 2 rodents (mouse and rat), a marsupial (opossum) and 3 invertebrates
      (fruit-fly, worm, and sponge) revealed that mitochondrial tRNA-lookalikes are
      prevalent in primates and the opossum but absent from the other analyzed
      organisms. 

PMID- 25849195
TI  - The clathrin adaptor AP-1 complex and Arf1 regulate planar cell polarity in vivo.
AB  - A key step in generating planar cell polarity (PCP) is the formation of
      restricted junctional domains containing Frizzled/Dishevelled/Diego (Fz/Dsh/Dgo)
      or Van Gogh/Prickle (Vang/Pk) complexes within the same cell, stabilized via
      Flamingo (Fmi) across cell membranes. Although models have been proposed for how
      these complexes acquire and maintain their polarized localization, the machinery
      involved in moving core PCP proteins around cells remains unknown. We describe
      the AP-1 adaptor complex and Arf1 as major regulators of PCP protein trafficking
      in vivo. AP-1 and Arf1 disruption affects the accumulation of Fz/Fmi and Vang/Fmi
      complexes in the proximo-distal axis, producing severe PCP phenotypes. Using
      novel tools, we demonstrate a direct and specific Arf1 involvement in Fz
      trafficking in vivo. Moreover, we uncover a conserved Arf1 PCP function in
      vertebrates. Our data support a model whereby the trafficking machinery plays an
      important part during PCP establishment, promoting formation of polarized PCP
      core complexes in vivo. 

PMID- 25849197
TI  - Smart functional nucleic acid chimeras: enabling tissue specific RNA targeting
      therapy.
AB  - A major obstacle for effective utilization of therapeutic oligonucleotides such
      as siRNA, antisense, antimiRs etc. is to deliver them specifically to the target
      tissues. Toward this goal, nucleic acid aptamers are re-emerging as a prominent
      class of biomolecules capable of delivering target specific therapy and
      therapeutic monitoring by various molecular imaging modalities. This class of
      short oligonucleotide ligands with high affinity and specificity are selected
      from a large nucleic acid pool against a molecular target of choice. Poor
      cellular uptake of therapeutic oligonucleotides impedes gene-targeting efficacy
      in vitro and in vivo. In contrast, aptamer-oligonucleotide chimeras have shown
      the capacity to deliver siRNA, antimiRs, small molecule drugs etc. toward various
      targets and showed very promising results in various studies on different
      diseases models. However, to further improve the bio-stability of such chimeric
      conjugates, it is important to introduce chemically-modified nucleic acid
      analogs. In this review, we highlight the applications of nucleic acid aptamers
      for target specific delivery of therapeutic oligonucleotides. 

PMID- 25849200
TI  - Improved Electrochemical Performance of Fe-Substituted NaNi0.5Mn0.5O2 Cathode
      Materials for Sodium-Ion Batteries.
AB  - A series of O3-phase NaFe(x)(Ni0.5Mn0.5)(1-x)O2 (x = 0, 0.1, 0.2, 0.3, 0.4, and
      1) samples with different Fe contents was prepared and investigated as high
      capacity cathodic hosts of Na-ion batteries. The partial substitution of Ni and
      Mn with Fe in the O3-phase lattice can greatly improve the electrochemical
      performance and the structural stability. A NaFe0.2Mn0.4Ni0.4O2 cathode with an
      optimized Fe content of x = 0.2 can deliver an initial reversible capacity of 131
      mAh g(-1), a reversible capacity greater than 95% over 30 cycles, and a high rate
      capacity of 86 mAh g(-1) at 10 C in a voltage range of 2.0-4.0 V. The structural
      characterizations reveal that pristine NaMn0.5Ni0.5O2 and Fe-substituted
      NaFe0.2Mn0.4Ni0.4O2 lattices underwent different phase transformations from P3 to
      P3" and from P3 to OP2 phases, respectively, at high voltage interval. The as
      resulted OP2 phase by Fe substitution has smaller interslab distance (5.13 A)
      than the P3" phase (5.72 A), which suppresses the co-insertion of the solvent
      molecules, the electrolyte anions, or both and therefore enhances the cycling
      stability in the high voltage charge. This finding suggests a new strategy for
      creating cycle-stable transition-metal oxide cathodes for high-performance Na-ion
      batteries.

PMID- 25849198
TI  - Incomplete splicing of neutrophil-specific genes affects neutrophil development
      in a zebrafish model of poikiloderma with neutropenia.
AB  - Poikiloderma with neutropenia (PN) is a rare inherited disorder characterized by
      poikiloderma, facial dysmorphism, pachyonychia, short stature and neutropenia.
      The molecular testing of PN patients has identified mutations in the C16orf57
      gene, which encodes a protein referred to as USB1 (U Six Biogenesis 1). In this
      study, we developed a zebrafish model of PN by the microinjection of morpholino
      antisense oligos to suppress usb1 gene function. Severe morphological defects,
      including a bent tail, thin yolk extension and reduced body length, were
      predominant in the Usb1-suppressed embryos (morphants). We also observed
      significantly decreased number of neutrophils in the morphants by Sudan Black
      staining. Interestingly, the splicing of genes involved in neutrophil
      differentiation and development, such as mpx, ncf1, ela3l and npsn, was aberrant
      in the morphants. However, the splicing of haematopoietic precursors and
      erythroid-specific genes was unaltered. Importantly, the neutrophil defects were
      almost completely rescued by co-injection of ela3l mRNA, the most markedly
      affected gene in the morphants. Our study demonstrated a possible role of USB1 in
      modulating the tissue-specific gene splicing that eventually leads to the
      impaired development of neutrophils. This zebrafish model could serve as a
      valuable tool to investigate the causative role of USB1 in PN pathogenesis. 

PMID- 25849199
TI  - Domain movements during CCA-addition: a new function for motif C in the catalytic
      core of the human tRNA nucleotidyltransferases.
AB  - CCA-adding enzymes are highly specific RNA polymerases that synthesize and
      maintain the sequence CCA at the tRNA 3'-end. This nucleotide triplet is a
      prerequisite for tRNAs to be aminoacylated and to participate in protein
      biosynthesis. During CCA-addition, a set of highly conserved motifs in the
      catalytic core of these enzymes is responsible for accurate sequential nucleotide
      incorporation. In the nucleotide binding pocket, three amino acid residues form
      Watson-Crick-like base pairs to the incoming CTP and ATP. A reorientation of
      these templating amino acids switches the enzyme's specificity from CTP to ATP
      recognition. However, the mechanism underlying this essential structural
      rearrangement is not understood. Here, we show that motif C, whose actual
      function has not been identified yet, contributes to the switch in nucleotide
      specificity during polymerization. Biochemical characterization as well as EPR
      spectroscopy measurements of the human enzyme reveal that mutating the highly
      conserved amino acid position D139 in this motif interferes with AMP
      incorporation and affects interdomain movements in the enzyme. We propose a model
      of action, where motif C forms a flexible spring element modulating the relative
      orientation of the enzyme's head and body domains to accommodate the growing 3'
      end of the tRNA. Furthermore, these conformational transitions initiate the
      rearranging of the templating amino acids to switch the specificity of the
      nucleotide binding pocket from CTP to ATP during CCA-synthesis. 

PMID- 25849201
TI  - Conformational Preadjustment in Aqueous Claisen Rearrangement Revealed by SITS
      QM/MM MD Simulations.
AB  - An efficient sampling method was implemented in QM/MM hybrid molecular
      simulations to study aliphatic Claisen rearrangement in aqueous solutions. On the
      basis of the computational results, the necessary conformational adjustment to
      trap the reactant into a favorable compact conformation specifically in water was
      observed. The conformational equilibrium was shown to be important to the
      elucidation of the "water-acceleration" effect of Claisen rearrangement. Thus, a
      two-step process of aqueous Claisen rearrangement was proposed. It was similar to
      the pseudodiaxial-pseudodiequatorial conformational equilibrium observed in the
      enzymatic reaction of chorismate acid but with explicit inclusion of the solvent
      coordinates to explain the solvation effects. Polarization was found to occur
      during the reactant conformational transition. A solvent with high cohesive
      energy density (CED) like water was suggested to accommodate compact conformers
      better, thus facilitating the following reaction by concentrating the real
      "active" reactant. The substituent effects also manifested, leading to varied
      conformational distributions of different substituted allyl vinyl ethers (AVEs).
      The application of the enhanced sampling method allowed a systematic analysis of
      thermodynamic information without loss of solvent coordinates. These data showed
      the conformational transition of AVEs was an entropy-driving process which was
      sensitive to the substituent, and enthalpy played an important role in the
      solvation effect on the conformational equilibrium. 

PMID- 25849202
TI  - The global inventor gap: distribution and equality of world-wide inventive
      effort, 1990-2010.
AB  - Applying distance-to-frontier analysis, we have used 2.9 million patents and
      population data to assess whether the relative capacity of world countries and
      major regions to create new knowledge and technology has become globally more
      equal or less equal between 1990 and 2010. We show with the Gini coefficient that
      the global distribution of inventors has become more equal between major
      countries and regions. However, this trend has been largely due to the improved
      performance of only two major countries, China and India. The worst performing
      regions, totalling a population of almost 2 billion, are actually falling behind.
      Our results suggest that substantial parts of the global population have fallen
      further behind countries at the global frontier in their ability to create new
      knowledge and inventions, and that the catch-up among the least developed and
      middle-income countries is highly uneven, prompting questions about the nature
      and future of the global knowledge economy. 

PMID- 25849204
TI  - Does interdisciplinary and multiprofessional undergraduate education increase
      students' self-confidence and knowledge toward palliative care? Evaluation of an
      undergraduate curriculum design for palliative care at a German academic
      hospital.
AB  - BACKGROUND: Undergraduate palliative care education (UPCE) became mandatory in
      Germany by 2013. The training in Mainz, addressing fifth-year (5Y) medical
      students, emphasizes transfer of knowledge and skills. In this study we assessed
      students' knowledge and students' self-estimation of self-confidence in
      palliative care (PC) according to Bandura's concept of self-efficacy. OBJECTIVE:
      The study objective was to evaluate the effects of the Mainz UPCE on students'
      self-confidence regarding important domains in PC. METHODS: We conducted a
      prospective questionnaire-based cohort study with a pre-post design. 5Y medical
      students (n=329) were asked for self-estimation concerning knowledge, somatic
      aspects, spiritual and psychological aspects before and after a 7x90-minute
      teaching course. To assess knowledge, students completed a multiple choice
      examination at the end of the term. RESULTS: Overall, 156 students completed
      matched surveys at both points of measurement. The majority of these students
      felt more confident after the course than before in all aspects of PC (p<0.0001).
      All students passed the exam with average scores greater than 90%. CONCLUSION: A
      7x90-minute interactive tutorial in PC for 5Y medical students is feasible and
      improves both self-efficacy and knowledge of core PC issues. Whether the effects
      of the course are long-lasting is the objective for further research.

PMID- 25849205
TI  - Doublecortin is widely expressed in the developing and adult retina of sharks.
AB  - Doublecortin (DCX) is a microtubule-associated protein that has been considered a
      marker for neuronal precursors and young migrating neurons during the development
      of the central nervous system and in adult neurogenic niches. The retina of
      fishes represents an accessible, continuously growing and highly structured
      (layered) part of the central nervous system and, therefore, offers an
      exceptional model to extend our knowledge on the possible role of DCX in
      promoting neurogenesis and migration to appropriate layers. We have analyzed the
      distribution of DCX in the embryonic and postembryonic retina of a small shark,
      the lesser spotted dogfish Scyliorhinus canicula, by means of
      immunohistochemistry. We investigated the relationship between DCX expression and
      the neurogenic state of DCX-labeled cells by exploring its co-localization with
      the proliferation marker PCNA (proliferating cell nuclear antigen) and the marker
      of neuronal differentiation HuC/D. Since radially migrating neurons use radial
      glial fibers as substrate, we explored the possible correlation between DCX
      expression and cell migration along radial glia by comparing its expression with
      that of the glial marker GFAP (glial fibrillary acidic protein). Additionally, we
      characterized DCX-expressing cells by double immunocytochemistry using antibodies
      against Calbindin (a marker for mature bipolar and horizontal cells in this
      species) and Pax6, which has been proposed as a regulator of cell proliferation,
      cell differentiation, and neuron diversification in the neural retina of sharks.
      Strong DCX immunoreactivity was observed in immature cells and cell processes, at
      a time when retinal cells were not yet organized into different laminae. DCX was
      also found in subsets of mature ganglion, amacrine, bipolar and horizontal cells
      long after they had exited the cell cycle, a pattern that was maintained in
      juveniles and adults. Our results on DCX expression in the retina are compatible
      with a role for DCX in cell migration within the immature retina, and in dynamic
      neuronal plasticity in the mature retina. We also provide evidence of DCX
      expression in discrete cells in the retinal pigment epithelium of prehatching
      embryos and juveniles, which suggest that retinal pigmented epithelial cells in
      sharks, as in mammals, have an intrinsic capacity to proliferate and
      differentiate into cells with neural identity. 

PMID- 25849206
TI  - Cellular size as a means of tracking mTOR activity and cell fate of CD4+ T cells
      upon antigen recognition.
AB  - mTOR is a central integrator of metabolic and immunological stimuli, dictating
      immune cell activation, proliferation and differentiation. In this study, we
      demonstrate that within a clonal population of activated T cells, there exist
      both mTORhi and mTORlo cells exhibiting highly divergent metabolic and
      immunologic functions. By taking advantage of the role of mTOR activation in
      controlling cellular size, we demonstrate that upon antigen recognition, mTORhi
      CD4+ T cells are destined to become highly glycolytic effector cells. Conversely,
      mTORlo T cells preferentially develop into long-lived cells that express high
      levels of Bcl-2, CD25, and CD62L. Furthermore, mTORlo T cells have a greater
      propensity to differentiate into suppressive Foxp3+ T regulatory cells, and this
      paradigm was also observed in human CD4+ T cells. Overall, these studies provide
      the opportunity to track the development of effector and memory T cells from
      naive precursors, as well as facilitate the interrogation of immunologic and
      metabolic programs that inform these fates. 

PMID- 25849207
TI  - ALV-J GP37 molecular analysis reveals novel virus-adapted sites and three
      tyrosine-based Env species.
AB  - Compared to other avian leukosis viruses (ALV), ALV-J primarily induces myeloid
      leukemia and hemangioma and causes significant economic loss for the poultry
      industry. The ALV-J Env protein is hypothesized to be related to its unique
      pathogenesis. However, the molecular determinants of Env for ALV-J pathogenesis
      are unclear. In this study, we compared and analyzed GP37 of ALV-J Env and the
      EAV-HP sequence, which has high homology to that of ALV-J Env. Phylogenetic
      analysis revealed five groups of ALV-J GP37 and two novel ALV-J Envs with endemic
      GP85 and EAV-HP-like GP37. Furthermore, at least 15 virus-adapted mutations were
      detected in GP37 compared to the EAV-HP sequence. Further analysis demonstrated
      that three tyrosine-based motifs (YxxM, ITIM (immune tyrosine-based inhibitory
      motif) and ITAM-like (immune tyrosine-based active motif like)) associated with
      immune disease and oncogenesis were found in the cytoplasmic tail of GP37. Based
      on the potential function and distribution of these motifs in GP37, ALV-J Env was
      grouped into three species, inhibitory Env, bifunctional Env and active Env.
      Accordingly, 36.91%, 61.74% and 1.34% of ALV-J Env sequences from GenBank are
      classified as inhibitory, bifunctional and active Env, respectively.
      Additionally, the Env of the ALV-J prototype strain, HPRS-103, and 17 of 18 EAV
      HP sequences belong to the inhibitory Env. And models for signal transduction of
      the three ALV-J Env species were predicted. Our findings and models provide novel
      insights for identifying the roles and molecular mechanism of ALV-J Env in the
      unique pathogenesis of ALV-J. 

PMID- 25849208
TI  - Dynamical System Modeling of Immune Reconstitution after Allogeneic Stem Cell
      Transplantation Identifies Patients at Risk for Adverse Outcomes.
AB  - Systems that evolve over time and follow mathematical laws as they evolve are
      called dynamical systems. Lymphocyte recovery and clinical outcomes in 41
      allograft recipients conditioned using antithymocyte globulin (ATG) and 4.5-Gy
      total body irradiation were studied to determine if immune reconstitution could
      be described as a dynamical system. Survival, relapse, and graft-versus-host
      disease (GVHD) were not significantly different in 2 cohorts of patients
      receiving different doses of ATG. However, donor-derived CD3(+) cell
      reconstitution was superior in the lower ATG dose cohort, and there were fewer
      instances of donor lymphocyte infusion (DLI). Lymphoid recovery was plotted in
      each individual over time and demonstrated 1 of 3 sigmoid growth patterns:
      Pattern A (n = 15) had rapid growth with high lymphocyte counts, pattern B (n =
      14) had slower growth with intermediate recovery, and pattern C (n = 10) had poor
      lymphocyte reconstitution. There was a significant association between lymphocyte
      recovery patterns and both the rate of change of donor-derived CD3(+) at day 30
      after stem cell transplantation (SCT) and clinical outcomes. GVHD was observed
      more frequently with pattern A, relapse and DLI more so with pattern C, with a
      consequent survival advantage in patients with patterns A and B. We conclude that
      evaluating immune reconstitution after SCT as a dynamical system may
      differentiate patients at risk of adverse outcomes and allow early intervention
      to modulate that risk. 

PMID- 25849209
TI  - Balanced sparse model for tight frames in compressed sensing magnetic resonance
      imaging.
AB  - Compressed sensing has shown to be promising to accelerate magnetic resonance
      imaging. In this new technology, magnetic resonance images are usually
      reconstructed by enforcing its sparsity in sparse image reconstruction models,
      including both synthesis and analysis models. The synthesis model assumes that an
      image is a sparse combination of atom signals while the analysis model assumes
      that an image is sparse after the application of an analysis operator. Balanced
      model is a new sparse model that bridges analysis and synthesis models by
      introducing a penalty term on the distance of frame coefficients to the range of
      the analysis operator. In this paper, we study the performance of the balanced
      model in tight frame based compressed sensing magnetic resonance imaging and
      propose a new efficient numerical algorithm to solve the optimization problem. By
      tuning the balancing parameter, the new model achieves solutions of three models.
      It is found that the balanced model has a comparable performance with the
      analysis model. Besides, both of them achieve better results than the synthesis
      model no matter what value the balancing parameter is. Experiment shows that our
      proposed numerical algorithm constrained split augmented Lagrangian shrinkage
      algorithm for balanced model (C-SALSA-B) converges faster than previously
      proposed algorithms accelerated proximal algorithm (APG) and alternating
      directional method of multipliers for balanced model (ADMM-B). 

PMID- 25849210
TI  - Stoichiometric determination of nitrate fate in agricultural ecosystems during
      rainfall events.
AB  - Ecologists have found a close relationship between the concentrations of nitrate
      (NO3-) and dissolved organic carbon (DOC) in ecosystems. However, it is difficult
      to determine the NO3- fate exactly because of the low coefficient in the
      constructed relationship. In the present paper, a negative power-function
      equation (r(2) = 0.87) was developed by using 411 NO3- data points and DOC:NO3-
      ratios from several agricultural ecosystems during different rainfall events. Our
      analysis of the stoichiometric method reveals several observations. First, the
      NO3- concentration demonstrated the largest changes when the DOC:NO3- ratio
      increased from 1 to 10. Second, the biodegradability of DOC was an important
      factor in controlling the NO3- concentration of agricultural ecosystems. Third,
      sediment was important not only as a denitrification site, but also as a major
      source of DOC for the overlying water. Fourth, a high DOC concentration was able
      to maintain a low NO3- concentration in the groundwater. In conclusion, this new
      stoichiometric method can be used for the accurate estimation and analysis of NO3
      concentrations in ecosystems.

PMID- 25849211
TI  - Submicroscopic and asymptomatic Plasmodium falciparum and Plasmodium vivax
      infections are common in western Thailand - molecular and serological evidence.
AB  - BACKGROUND: Malaria is a public health problem in parts of Thailand, where
      Plasmodium falciparum and Plasmodium vivax are the main causes of infection. In
      the northwestern border province of Tak parasite prevalence is now estimated to
      be less than 1% by microscopy. Nonetheless, microscopy is insensitive at low
      level parasitaemia. The objective of this study was to assess the current
      epidemiology of falciparum and vivax malaria in Tak using molecular methods to
      detect exposure to and infection with parasites; in particular, the prevalence of
      asymptomatic infections and infections with submicroscopic parasite levels.
      METHODS: Three-hundred microlitres of whole blood from finger-prick were
      collected into capillary tubes from residents of a sentinel village and from
      patients at a malaria clinic. Pelleted cellular fractions were screened by
      quantitative PCR to determine parasite prevalence, while plasma was probed on a
      protein microarray displaying hundreds of P. falciparum and P. vivax proteins to
      obtain antibody response profiles in those individuals. RESULTS: Of 219 samples
      from the village, qPCR detected 25 (11.4%) Plasmodium sp. infections, of which
      92% were asymptomatic and 100% were submicroscopic. Of 61 samples from the clinic
      patients, 27 (44.3%) were positive by qPCR, of which 25.9% had submicroscopic
      parasite levels. Cryptic mixed infections, misdiagnosed as single-species
      infections by microscopy, were found in 7 (25.9%) malaria patients. All sample
      donors, parasitaemic and non-parasitaemic alike, had serological evidence of
      parasite exposure, with 100% seropositivity to at least 54 antigens. Antigens
      significantly associated with asymptomatic infections were P. falciparum MSP2,
      DnaJ protein, putative E1E2 ATPase, and three others. CONCLUSION: These findings
      suggest that parasite prevalence is higher than currently estimated by local
      authorities based on the standard light microscopy. As transmission levels drop
      in Thailand, it may be necessary to employ higher throughput and sensitivity
      methods for parasite detection in the phase of malaria elimination.

PMID- 25849212
TI  - Heterogeneity of equilibrium molten globule state of cytochrome c induced by weak
      salt denaturants under physiological condition.
AB  - While many proteins are recognized to undergo folding via intermediate(s), the
      heterogeneity of equilibrium folding intermediate(s) along the folding pathway is
      less understood. In our present study, FTIR spectroscopy, far- and near-UV
      circular dichroism (CD), ANS and tryptophan fluorescence, near IR absorbance
      spectroscopy and dynamic light scattering (DLS) were used to study the structural
      and thermodynamic characteristics of the native (N), denatured (D) and
      intermediate state (X) of goat cytochorme c (cyt-c) induced by weak salt
      denaturants (LiBr, LiCl and LiClO4) at pH 6.0 and 25 degrees C. The LiBr-induced
      denaturation of cyt-c measured by Soret absorption (Deltaepsilon400) and CD
      ([theta]409), is a three-step process, N <-> X <-> D. It is observed that the X
      state obtained along the denaturation pathway of cyt-c possesses common
      structural and thermodynamic characteristics of the molten globule (MG) state.
      The MG state of cyt-c induced by LiBr is compared for its structural and
      thermodynamic parameters with those found in other solvent conditions such as
      LiCl, LiClO4 and acidic pH. Our observations suggest: (1) that the LiBr-induced
      MG state of cyt-c retains the native Met80-Fe(III) axial bond and Trp59
      propionate interactions; (2) that LiBr-induced MG state of cyt-c is more compact
      retaining the hydrophobic interactions in comparison to the MG states induced by
      LiCl, LiClO4 and 0.5 M NaCl at pH 2.0; and (3) that there exists heterogeneity of
      equilibrium intermediates along the unfolding pathway of cyt-c as highly ordered
      (X1), classical (X2) and disordered (X3), i.e., D <-> X3 <-> X2 <-> X1 <-> N. 

PMID- 25849213
TI  - Functional characterization of zebrafish (Danio rerio) Bcl10.
AB  - The complexes formed by BCL10, MALT1 and specific members of the family of CARMA
      proteins (CBM complex), have recently focused much attention because they
      represent a central hub regulating activation of the transcription factor NF
      kappaB following various cellular stimulations. In this manuscript, we report the
      functional characterization of a Danio rerio 241 amino acids polypeptide ortholog
      of the Caspase recruiting domain (CARD)-containing protein BCL10. Biochemical
      studies show that zebrafish Bcl10 (zBcl10) dimerizes and binds to components of
      the CBM complex. Fluorescence microscopy observations demonstrate that zBcl10
      forms cytoplasmic filaments similar to that formed by human BCL10 (hBCL10).
      Functionally, in human cells zBcl10 is more effective in activating NF-kappaB
      compared to hBCL10, possibly due to the lack of carboxy-terminal inhibitory
      serine residues present in the human protein. Also, depletion experiments carried
      out through expression of short hairpin RNAs targeting hBCL10 indicate that
      zBcl10 can functionally replace the human protein. Finally, we show that the
      zebrafish cell line PAC2 is suitable to carry out reporter assays for monitoring
      the activation state of NF- kB transcription factor. In conclusion, this work
      shows that zebrafish may excellently serve as a model organism to study complex
      and intricate signal transduction pathways, such as those that control NF-kappaB
      activation. 

PMID- 25849215
TI  - Correction: P2X7 mediates ATP-driven invasiveness in prostate cancer cells.

PMID- 25849214
TI  - Microparticles release by adipocytes act as "find-me" signals to promote
      macrophage migration.
AB  - Macrophage infiltration of adipose tissue during weight gain is a central event
      leading to the metabolic complications of obesity. However, what are the
      mechanisms attracting professional phagocytes to obese adipose tissue remains
      poorly understood. Here, we demonstrate that adipocyte-derived microparticles
      (MPs) are critical "find-me" signals for recruitment of monocytes and
      macrophages. Supernatants from stressed adipocytes stimulated the attraction of
      monocyte cells and primary macrophages. The activation of caspase 3 was required
      for release of these signals. Adipocytes exposed to saturated fatty acids showed
      marked release of MPs into the supernatant while common genetic mouse models of
      obesity demonstrate high levels of circulating adipocyte-derived MPs. The release
      of MPs was highly regulated and dependent on caspase 3 and Rho-associated kinase.
      Further analysis identified these MPs as a central chemoattractant in vitro and
      in vivo. In addition, intravenously transplanting circulating MPs from the ob/ob
      mice lead to activation of monocytes in circulation and adipose tissue of the
      wild type mice. These data identify adipocyte-derived MPs as novel "find me"
      signals that contributes to macrophage infiltration associated with obesity. 

PMID- 25849216
TI  - The evolution of WRKY transcription factors.
AB  - BACKGROUND: The availability of increasing numbers of sequenced genomes has
      necessitated a re-evaluation of the evolution of the WRKY transcription factor
      family. Modern day plants descended from a charophyte green alga that colonized
      the land between 430 and 470 million years ago. The first charophyte genome
      sequence from Klebsormidium flaccidum filled a gap in the available genome
      sequences in the plant kingdom between unicellular green algae that typically
      have 1-3 WRKY genes and mosses that contain 30-40. WRKY genes have been
      previously found in non-plant species but their occurrence has been difficult to
      explain. RESULTS: Only two WRKY genes are present in the Klebsormidium flaccidum
      genome and the presence of a Group IIb gene was unexpected because it had
      previously been thought that Group IIb WRKY genes first appeared in mosses. We
      found WRKY transcription factor genes outside of the plant lineage in some
      diplomonads, social amoebae, fungi incertae sedis, and amoebozoa. This patchy
      distribution suggests that lateral gene transfer is responsible. These lateral
      gene transfer events appear to pre-date the formation of the WRKY groups in
      flowering plants. Flowering plants contain proteins with domains typical for both
      resistance (R) proteins and WRKY transcription factors. R protein-WRKY genes have
      evolved numerous times in flowering plants, each type being restricted to
      specific flowering plant lineages. These chimeric proteins contain not only novel
      combinations of protein domains but also novel combinations and numbers of WRKY
      domains. Once formed, R protein WRKY genes may combine different components of
      signalling pathways that may either create new diversity in signalling or
      accelerate signalling by short circuiting signalling pathways. CONCLUSIONS: We
      propose that the evolution of WRKY transcription factors includes early lateral
      gene transfers to non-plant organisms and the occurrence of algal WRKY genes that
      have no counterparts in flowering plants. We propose two alternative hypotheses
      of WRKY gene evolution: The "Group I Hypothesis" sees all WRKY genes evolving
      from Group I C-terminal WRKY domains. The alternative "IIa + b Separate
      Hypothesis" sees Groups IIa and IIb evolving directly from a single domain algal
      gene separate from the Group I-derived lineage.

PMID- 25849218
TI  - Copper-catalyzed radical methylation/C-H amination/oxidation cascade for the
      synthesis of quinazolinones.
AB  - A copper-catalyzed radical methylation/sp(3) C-H amination/oxidation reaction for
      the facile synthesis of quinazolinone was developed. In this cascade reaction,
      dicumyl peroxide acts not only as a useful oxidant but also as an efficient
      methyl source. Notably, a methyl radical, generated from peroxide, was confirmed
      by electron paramagnetic resonance for the first time. 

PMID- 25849217
TI  - Common variants at 9q22.33, 14q13.3, and ATM loci, and risk of differentiated
      thyroid cancer in the French Polynesian population.
AB  - BACKGROUND: French Polynesia has one of the highest incidence rates of thyroid
      cancer worldwide. Relationships with the atmospheric nuclear weapons tests and
      other environmental, biological, or behavioral factors have already been
      reported, but genetic susceptibility has yet to be investigated. We assessed the
      contribution of polymorphisms at the 9q22.33 and 14q13.3 loci identified by GWAS,
      and within the DNA repair gene ATM, to the risk of differentiated thyroid cancer
      (DTC) in 177 cases and 275 matched controls from the native population. PRINCIPAL
      FINDINGS: For the GWAS SNP rs965513 near FOXE1, an association was found between
      genotypes G/A and A/A, and risk of DTC. A multiplicative effect of allele A was
      even noted. An excess risk was also observed in individuals carrying two long
      alleles of the poly-alanine tract expansion in FOXE1, while no association was
      observed with rs1867277 falling in the promoter region of the gene. In contrast,
      the GWAS SNP rs944289 (NKX2-1) did not show any significant association. Although
      the missense substitution D1853N (rs1801516) in ATM was rare in the population,
      carriers of the minor allele (A) also showed an excess risk. The relationships
      between these five polymorphisms and the risk of DTC were not contingent on the
      body surface area, body mass index, ethnicity or dietary iodine intake. However,
      an interaction was evidenced between the thyroid radiation dose and rs944289.
      SIGNIFICANCE: A clear link could not be established between the high incidence in
      French Polynesia and the studied polymorphisms, involved in susceptibility to DTC
      in other populations. Important variation in allele frequencies was observed in
      the Polynesian population as compared to the European populations. For FOXE1
      rs965513, the direction of association and the effect size was similar to that
      observed in other populations, whereas for ATM rs1801516, the minor allele was
      associated to an increased risk in the Polynesian population and with a decreased
      risk in the European population.

PMID- 25849219
TI  - Bringing macromolecules into cells and evading endosomes by oxidized carbon
      nanoparticles.
AB  - A great challenge exists in finding safe, simple, and effective delivery
      strategies to bring matters across cell membrane. Popular methods such as viral
      vectors, positively charged particles and cell penetrating peptides possess some
      of the following drawbacks: safety issues, lysosome trapping, limited loading
      capacity, and toxicity, whereas electroporation produces severe damages on both
      cargoes and cells. Here, we show that a serendipitously discovered, relatively
      nontoxic, water dispersible, stable, negatively charged, oxidized carbon
      nanoparticle, prepared from graphite, could deliver macromolecules into cells,
      without getting trapped in a lysosome. The ability of the particles to induce
      transient pores on lipid bilayer membranes of cell-sized liposomes was
      demonstrated. Delivering 12-base-long pyrrolidinyl peptide nucleic acids with d
      prolyl-(1S,2S)-2-aminocyclopentanecarboxylic acid backbone (acpcPNA)
      complementary to the antisense strand of the NF-kappaB binding site in the
      promoter region of the Il6 gene into the macrophage cell line, RAW 264.7, by our
      particles resulted in an obvious accumulation of the acpcPNAs in the nucleus and
      decreased Il6 mRNA and IL-6 protein levels upon stimulation. We anticipate this
      work to be a starting point in a new drug delivery strategy, which involves the
      nanoparticle that can induce a transient pore on the lipid bilayer membrane. 

PMID- 25849220
TI  - Meningiomas of the cerebellopontine angle: radiological differences in tumors
      with internal auditory canal involvement and their influence on surgical outcome.
AB  - This study explored the clinical, radiological, and pathological characteristics
      of cerebellopontine angle (CPA) meningiomas with internal auditory canal (IAC)
      involvement. The pre- and postoperative MR images of 193 consecutive patients
      with pathologically diagnosed meningioma centered around the IAC were analyzed,
      focusing on changes in the IAC, maximal axial tumor volume, peritumoral brain
      edema, and postoperative residual tumor. Patient age, sex, tumor volume,
      postoperative residual tumor, and pathological subtype were compared in patients
      with and without IAC involvement by the tumor and among the different types of
      IAC involvement. The results showed that the 71 patients (36.8%) with IAC
      involvement had a higher ratio of peritumoral edema (chi(2)=5.922, P=0.015),
      postoperative residual tumor (chi(2)=22.183, P< 0.001), and a predominance of the
      meningothelial subtype (chi(2)=5.89, P=0 .015). Peritumoral edema was a risk
      factor for IAC involvement (P=0.016, OR=2.186). Radiologically, IAC involvement
      could be distinguished as intruding (31%, 22/71), filled (29.6%, 21/71), and
      dilated (39.4%, 28/71). Patients with intruding IAC were significantly older
      (54.5 +/- 9.54 years, P=0.021) and had the lowest postoperative residual tumor
      values (42%, chi(2)=7.865, P=0.005), while those with filled IAC were more likely
      to be female (95%, chi(2)=9.404, P=0.009).Our observations provide the basis for
      a morphological classification of IAC involvement by CPA meningiomas and further
      insight into the clinical features of these tumors.

PMID- 25849221
TI  - Molecular subtyping for clinically defined breast cancer subgroups.
AB  - INTRODUCTION: Breast cancer is commonly classified into intrinsic molecular
      subtypes. Standard gene centering is routinely done prior to molecular subtyping,
      but it can produce inaccurate classifications when the distribution of
      clinicopathological characteristics in the study cohort differs from that of the
      training cohort used to derive the classifier. METHODS: We propose a subgroup
      specific gene-centering method to perform molecular subtyping on a study cohort
      that has a skewed distribution of clinicopathological characteristics relative to
      the training cohort. On such a study cohort, we center each gene on a specified
      percentile, where the percentile is determined from a subgroup of the training
      cohort with clinicopathological characteristics similar to the study cohort. We
      demonstrate our method using the PAM50 classifier and its associated University
      of North Carolina (UNC) training cohort. We considered study cohorts with skewed
      clinicopathological characteristics, including subgroups composed of a single
      prototypic subtype of the UNC-PAM50 training cohort (n = 139), an external
      estrogen receptor (ER)-positive cohort (n = 48) and an external triple-negative
      cohort (n = 77). RESULTS: Subgroup-specific gene centering improved prediction
      performance with the accuracies between 77% and 100%, compared to accuracies
      between 17% and 33% from standard gene centering, when applied to the prototypic
      tumor subsets of the PAM50 training cohort. It reduced classification error rates
      on the ER-positive (11% versus 28%; P = 0.0389), the ER-negative (5% versus 41%;
      P < 0.0001) and the triple-negative (11% versus 56%; P = 0.1336) subgroups of the
      PAM50 training cohort. In addition, it produced higher accuracy for subtyping
      study cohorts composed of varying proportions of ER-positive versus ER-negative
      cases. Finally, it increased the percentage of assigned luminal subtypes on the
      external ER-positive cohort and basal-like subtype on the external triple
      negative cohort. CONCLUSIONS: Gene centering is often necessary to accurately
      apply a molecular subtype classifier. Compared with standard gene centering, our
      proposed subgroup-specific gene centering produced more accurate molecular
      subtype assignments in a study cohort with skewed clinicopathological
      characteristics relative to the training cohort.

PMID- 25849222
TI  - The effect of desflurane on neuronal communication at a central synapse.
AB  - Although general anesthetics are thought to modify critical neuronal functions,
      their impact on neuronal communication has been poorly examined. We have
      investigated the effect induced by desflurane, a clinically used general
      anesthetic, on information transfer at the synapse between mossy fibers and
      granule cells of cerebellum, where this analysis can be carried out extensively.
      Mutual information values were assessed by measuring the variability of
      postsynaptic output in relationship to the variability of a given set of
      presynaptic inputs. Desflurane synchronized granule cell firing and reduced
      mutual information in response to physiologically relevant mossy fibers patterns.
      The decrease in spike variability was due to an increased postsynaptic membrane
      excitability, which made granule cells more prone to elicit action potentials,
      and to a strengthened synaptic inhibition, which markedly hampered membrane
      depolarization. These concomitant actions on granule cells firing indicate that
      desflurane re-shapes the transfer of information between neurons by providing a
      less informative neurotransmission rather than completely silencing neuronal
      activity. 

PMID- 25849223
TI  - Once-daily fluticasone furoate/vilanterol 100/25 mcg versus twice daily
      combination therapies in COPD - mixed treatment comparisons of clinical efficacy.
AB  - BACKGROUND: Fluticasone furoate (FF)/vilanterol (VI) 100/25 mcg is a once-daily
      inhaled corticosteroid (ICS)/long-acting beta2 agonist (LABA) treatment approved
      in the United States, Canada and Europe for the long-term maintenance therapy of
      COPD. We report data from mixed treatment comparisons (MTC) of once-daily FF/VI
      against established twice-daily ICS/LABA combination therapies on clinical
      efficacy outcomes. METHODS: Data from 33 parallel-group randomised controlled
      trials (RCTs) of ICS/LABAs, of >=8 weeks' duration in patients >=12 years of age
      with COPD, identified by systematic review, were analysed using covariate
      adjusted Bayesian hierarchical models for three efficacy outcomes. Lung function,
      assessed by change from baseline in forced expiratory volume in one second
      (FEV1), was the outcome of primary interest (n = 28 studies). Secondary
      objectives were assessment of annual rate of moderate/severe exacerbations (n =
      15) and patient-reported health status, measured by change from baseline in St
      George's Respiratory Questionnaire (SGRQ) Total score (n = 20). Overall, 25
      different treatments were included in the MTC; we report findings, including
      probabilities of non-inferiority, for comparisons of once-daily FF/VI 100/25 mcg
      with twice-daily fluticasone propionate (FP)/salmeterol (SAL) 500/50 mcg and
      budesonide (BUD)/formoterol (FORM) 400/12 mcg. RESULTS: For FEV1, FF/VI 100/25
      mcg demonstrated >99% probability of non-inferiority to FP/SAL 500/50 mcg and
      BUD/FORM 400/12 mcg using a 50 mL margin. For annual rate of moderate/severe
      exacerbations, FF/VI 100/25 mcg demonstrated 73% and 77% probability of non
      inferiority to FP/SAL 500/50 mcg and BUD/FORM 400/12 mcg, respectively, using a
      10% rate ratio margin. For SGRQ Total score, the corresponding probabilities of
      non-inferiority were 99% and 98%, respectively, on a 2-unit margin. Significant
      covariate effects were identified: increased age was associated with
      deterioration in FEV1 and reduced exacerbation frequency; shorter study duration
      was associated with reduced exacerbation frequency. CONCLUSIONS: FF/VI 100/25 mcg
      was comparable with corresponding doses of FP/SAL and BUD/FORM on lung function
      and health status outcomes. Non-inferiority on moderate/severe exacerbation rate
      was not demonstrated to the same degree of confidence, though observed rates were
      similar. Model limitations include a weak treatment network for the exacerbation
      analysis and variability across the included studies. Our data support previous
      RCT findings suggesting that the efficacy of FF/VI 100/25 mcg on lung function
      and health status in COPD is comparable with twice-daily ICS/LABAs.

PMID- 25849224
TI  - Adherence to Oral Medications for Hypertension and Diabetes in Veterans with
      Comorbid Airflow Limitation.
AB  - RATIONALE: Diabetes and hypertension are common among patients with airflow
      limitation and contribute to cardiovascular (CV) mortality, one of the leading
      causes of death among patients with airflow limitation. OBJECTIVES: Our goal was
      to examine the association of severity of airflow limitation with adherence to
      medications for hypertension and diabetes. METHODS: We identified 7,359 veterans
      with hypertension and/or diabetes in the Veterans Integrated Service Network-20.
      Entry date into the cohort was defined as the date of a patient's first pulmonary
      function testing (PFT). Diagnostic codes (ICD-9), PFT, and pharmacy data were
      available via the electronic medical record or via direct interrogation of PFT
      equipment. Our primary exposure was airflow limitation defined as FEV1 >= 80%
      predicted (normal), 80 > FEV1 >= 50% predicted (mild/moderate), 50 > FEV1 >= 30%
      predicted (severe), and FEV1 < 30% predicted (very severe). We assessed adherence
      using a validated method based on electronic pharmacy refill data and defined
      adherence as >= 80% medication possession for the period 6-12 months after
      enrollment. Medications of interest included beta-blockers, calcium channel
      blockers, thiazides, and angiotensin-converting-enzyme inhibitors for patients
      with hypertension, and metformin and sulfonylureas for patients with diabetes. We
      used logistic regression models to assess the association between severity of
      airflow limitation and adherence, adjusted for demographics, health behaviors,
      and comorbidities. MEASUREMENTS AND MAIN RESULTS: Overall adherence was poor
      (44.6-55.1%). Among patients with hypertension, when compared with subjects with
      normal FEV1, subjects with each category lower of FEV1 were less adherent to beta
      blockers, with an odds ratio (OR) of 0.87 (95% confidence interval [CI], 0.80
      0.95); calcium channel blockers, with an OR of 0.83 (95% CI, 0.74-0.93); and
      angiotensin-converting-enzyme inhibitors with an OR of 0.91 (95% CI, 0.84-0.99).
      Airflow limitation was not associated with adherence to thiazides. Among patients
      with diabetes, we found no significant association of FEV1 with adherence,
      although a similar lower trend with increasing airflow limitation. In a
      sensitivity analysis limited to patients with chronic obstructive pulmonary
      disease, we found a nonstatistically significant trend for decreased adherence to
      beta-blockers, calcium channel blockers, and angiotensin-converting-enzyme
      inhibitors in subjects with higher GOLD (Global Initiative for Chronic
      Obstructive Lung Disease) stage. CONCLUSIONS: Severity of airflow limitation is
      associated with decreased adherence to beta-blockers, calcium channel blockers,
      and angiotensin-converting-enzyme inhibitors. The decreased adherence to these
      medications may be related to adverse effects on symptoms in patients with lung
      disease, and may partially explain excess CV mortality in these patients.

PMID- 25849225
TI  - Genetic depletion and pharmacological targeting of alphav integrin in breast
      cancer cells impairs metastasis in zebrafish and mouse xenograft models.
AB  - INTRODUCTION: Increased expression of alphav integrins is frequently associated
      with tumor cell adhesion, migration, invasion and metastasis, and correlates with
      poor prognosis in breast cancer. However, the mechanism by which alphav integrins
      can enhance breast cancer progression is still largely unclear. The effects of
      therapeutic targeting of alphav integrins in breast cancer also have yet to be
      investigated. METHODS: We knocked down alphav integrin in MDA-MB-231 and MCF10A
      M4 breast cancer cells, or treated these cells with the alphav antagonist
      GLPG0187. The effects of alphav integrin depletion on mesenchymal markers,
      transforming growth factor-beta (TGF-beta)/Smad signaling and TGF-beta-induced
      target gene expression were analyzed in MDA-MB-231 cells by RNA analysis or
      Western blotting. The function of alphav integrin on breast cancer cell migration
      was investigated by transwell assay in vitro, and its effect on breast cancer
      progression was assessed by both zebrafish and mouse xenografts in vivo. In the
      mouse model, GLPG0187 was administered separately, or in combination with the
      standard-of-care anti-resorptive agent zoledronate and the chemotherapeutic drug
      paclitaxel, to study the effects of combinational treatments on breast cancer
      metastasis. RESULTS: Genetic interference and pharmacological targeting of alphav
      integrin with GLPG0187 in different breast cancer cell lines inhibited invasion
      and metastasis in the zebrafish or mouse xenograft model. Depletion of alphav
      integrin in MDA-MB-231 cells inhibited the expression of mesenchymal markers and
      the TGF-beta/Smad response. TGF-beta induced alphav integrin mRNA expression and
      alphav integrin was required for TGF-beta-induced breast cancer cell migration.
      Moreover, treatment of MDA-MB-231 cells with non-peptide RGD antagonist GLPG0187
      decreased TGF-beta signaling. In the mouse xenografts GLPG0187 inhibited the
      progression of bone metastasis. Maximum efficacy of inhibition of bone metastasis
      was achieved when GLPG0187 was combined with the standard-of-care metastatic
      breast cancer treatments. CONCLUSION: These findings show that alphav integrin is
      required for efficient TGF-beta/Smad signaling and TGF-beta-induced breast cancer
      cell migration, and for maintaining a mesenchymal phenotype of the breast cancer
      cells. Our results also provide evidence that targeting alphav integrin could be
      an effective therapeutic approach for treatment of breast cancer tumors and/or
      metastases that overexpress alphav integrin.

PMID- 25849227
TI  - EPR spin trapping evidence of radical intermediates in the photo-reduction of
      bicarbonate/CO2 in TiO2 aqueous suspensions.
AB  - Using the EPR spin trapping technique, we prove that simultaneous reactions take
      place in illuminated suspensions of TiO2 in aqueous carbonate solutions (pH ~ 7).
      The adsorbed HCO3(-) is reduced to formate as directly made evident by the
      detection of formate radicals (CO2(-)). In addition, the amount of OH radicals
      from the photo-oxidation of water shows a linear dependence on the concentration
      of bicarbonate, indicating that electron scavenging by HCO3(-) increases the
      lifetime of holes. In a weakly alkaline medium, photo-oxidation of HCO3(-)/CO3(2
      ) to CO3(-) interferes with the oxidation of water. A comparative analysis of
      different TiO2 samples shows that formation of CO2(-) is influenced by factors
      related to the nature of the surface, once expected surface area effects are
      accounted for. Modification of the TiO2 surface with noble metal nanoparticles
      does not have unequivocal benefits: the overall activity improves with Pd and Rh
      but not with Ru, which favours HCO3(-) photo-oxidation even at pH = 7. In
      general, identification of radical intermediates of oxidation and reduction
      reactions can provide useful mechanistic information that may be used in the
      development of photocatalytic systems for the reduction of CO2 also stored in the
      form of carbonates. 

PMID- 25849226
TI  - Mesenchymal chondrosarcoma of bone and soft tissue: a systematic review of 107
      patients in the past 20 years.
AB  - BACKGROUND: Mesenchymal chondrosarcoma(MCS) is a rare high-grade variant of
      chondrosarcoma. Consensus has not been reached on its optimal management.
      Resection with wide margins is usually recommended, but the effect of margins has
      been demonstrated by little positive evidence. Moreover, the effectiveness of
      adjuvant chemo- and/or radiotherapy remains controversial. OBJECTIVES: To
      describe the clinical characteristics and outcomes of MCS of bone and soft
      tissue, to assess the efficacies of surgery, chemotherapy and radiation, and
      finally to deliver a more appropriate therapy. MATERIALS AND METHODS: We reviewed
      EMBASE-, MEDLINE-, Cochrane-, Ovid- and PubMed-based to find out all cases of MCS
      of bone and soft tissue described between April 1994 and April 2014. Description
      of treatment and regular follow-up was required for each study. Language was
      restricted to English and Chinese. Issues of age, gender, location, metastasis,
      and treatment were all evaluated for each case. Kaplan-Meier Method and Cox
      Proportional Hazard Regression Model were used in the survival analysis. RESULTS:
      From the 630 identified publications, 18 meeting the inclusion criteria were
      selected, involving a total of 107 patients. Based on these data, the 5-, 10-and
      20-year overall survival are 55.0%, 43.5% and 15.7% respectively. The 5-, 10-, 20
      year event-free survival rates are 45.0%, 27.2% and 8.1%, respectively.
      Treatment without surgery is associated with poorer overall survival and event
      free survival. Negative surgical margins could significantly bring down the local
      recurrence rate and are associated with a higher event-free survival rate.
      Chemotherapy regime based on anthracyclines does not benefit the overall
      survival. The addition of radiation therapy is not significantly associated with
      the overall or event-free survival. However, we recommend radiation as the
      salvage therapy for patients with positive margin so as to achieve better local
      control. CONCLUSIONS: This review shows that surgery is essential in the
      management of MCS of bone and soft tissue. Appropriate adjuvant therapy may
      reduce local recurrence, but cannot benefit the overall survival.

PMID- 25849228
TI  - Viral shedding and susceptibility to oseltamivir in hospitalized
      immunocompromised patients with influenza in the Influenza Resistance Information
      Study (IRIS).
AB  - BACKGROUND: Immunocompromised patients are at greater risk of complicated
      influenza and may be more likely to develop antiviral resistance. This
      observational substudy of the Influenza Resistance Information Study
      (NCT00884117) aimed to study antiviral resistance in immunocompromised patients
      with influenza and characterize its effect on clinical and virological outcomes.
      METHODS: Eligible immunocompromised patients were aged >=1 year with a local
      rapid diagnostic or PCR test positive for influenza <=96 h after diagnosis and
      with influenza symptoms. Nasal and throat swabs were taken for RT-PCR analysis on
      day 1 and then every 3 days until patients were virus-free. Resistance was
      assessed by mutation-specific RT-PCR, phenotypic susceptibility analysis and
      Sanger sequencing. RESULTS: Of 42 patients enrolled, 29 (69%) were influenza
      positive (RT-PCR) on day 1: 18 adults and 11 children aged 1-12 years. Six
      patients were severely immunocompromised. On days 3, 6 and 9, most patients
      tested (18/24, 9/15 and 6/9, respectively) had not cleared the virus. Two of five
      patients assessed after day 9 continued shedding virus until day 15. H1N1pdm09
      viruses harbouring H275Y mutations were detected in post-baseline samples from
      four patients (aged 52-61 years), one of whom had prolonged viral shedding. No
      genotypic antiviral resistance was detected in the other 20 treated patients
      (prevalence of resistance, 17%). Correlation between level of immune compromise
      and resistance or outcomes could not be assessed. Ten patients (seven influenza
      positive) were admitted to intensive care and three died. CONCLUSIONS: In these
      patients with mild/moderate immunocompromise, emergence of oseltamivir-resistant
      viruses was not common. Severity of influenza symptoms ranged from mild to
      moderate, but correlation with level of compromise could not be determined.

PMID- 25849229
TI  - Sickness absence: a concern for all of us.

PMID- 25849230
TI  - Should blood glucose strips be used in type 2 diabetes?

PMID- 25849231
TI  - Undernutrition in older people in Australia.
AB  - Despite being preventable and treatable, undernutrition remains a problem for
      many older people in tertiary healthcare settings. Nurses have a crucial role in
      assisting people who are unable to eat independently and are uniquely positioned
      to implement solutions that will lead to better nutritional care. However, what
      is known about the management of undernutrition is not informing nursing
      practice. This study used action research, underpinned by the 'participatory
      world view', to address the theory-practice gap. Data and between-method
      triangulation were used to collect and analyse qualitative non-participant
      observations and action research group data. Set Up Ready For Dining (SURFD) was
      developed and implemented by nurses to improve patient mealtimes. Findings show
      that nursing practice in nutritional care is influenced by technique within the
      healthcare context that emphasises operational efficiency, and by the choices
      that nurses made around being the patient advocate during mealtimes. 

PMID- 25849232
TI  - The efficacy of feeding tubes: confirmation and loss.
AB  - Around 5% of hospital patients require enteral tube feeding, yet its efficacy and
      costs are poorly understood. The authors examined radio-opacity, reason for
      repeat X-ray and overall cost in consecutive patients having tubes confirmed by X
      ray when using polyvinylchloride (PVC) Ryles tubes versus CORFLO(r) (CORTRAK
      Medsystems) polyurethane tubes (PUTs); and confirmation method and reason for
      tube loss over an enteral episode. Despite higher PUT cost, because more Ryles
      tubes required re-X-ray +/- radio-contrast injection (0% compared with 26%,
      p=0.029), overall cost was almost identical (Corflo: L54.2 vs Ryles: L54.6).
      Confirmation of tube position by X-ray remains more common than pH (51% compared
      with 45%) and tube loss is mostly as a result of inadvertent patient removal
      (54%). These studies show that: a) when using X-ray confirmation, PUTs and PVC
      Ryles tube cost is similar; b) despite pH being taught as first-line
      confirmation, X-ray remains the most common method therefore PUT use may further
      reduce cost when staff and outcome costs are included. In addition, more reliable
      and repeatable bedside confirmation methods are required; c) most tube loss is
      potentially preventable by use of nasal bridles. Larger studies are required to
      establish baseline data on problems and cost-effectiveness of enteral tube
      feeding before intervention trials. 

PMID- 25849233
TI  - Contracting for enteral tube feeding.

PMID- 25849234
TI  - A CBT-based anxiety management workshop in first-episode psychosis.
AB  - When co-occurring with psychosis, anxiety can adversely affect social and
      occupational functioning and can cause debilitating levels of distress. This
      article describes a single-centre three-phase service development project
      culminating in the introduction of 1-day anxiety management workshops for service
      users of an Early Intervention for Psychosis Service (EIPS). The workshops, which
      were run by a mental health nurse and an assistant psychologist, attracted 12
      participants with a first episode of psychosis and co-morbid anxiety.
      Quantitative and qualitative measures demonstrated a statistically significant
      reduction (p<0.0005) in subjective anxiety levels following the intervention, and
      that participants felt they were likely to make use of the skills in the future.
      It can be concluded that such workshops are not only time-and cost-effective, but
      also valuable in delivering brief interventions based on cognitive behavioural
      therapy (CBT) to service users with a first episode of psychosis. 

PMID- 25849235
TI  - Disclosing a dyslexic identity.
AB  - Potential difficulties experienced by nursing students diagnosed with dyslexia
      can be minimised with the introduction of appropriate policies and guidance
      around reasonable adjustment and support. In order to access all relevant
      services, however, a student must actively decide to disclose their dyslexic
      identity to relevant faculty personnel. Disclosure of such personal information
      is a complex matter and, critically, requires a receptive environment where
      diversity and disability are embraced in a positive and meaningful way. The act
      of disclosure for the most part has previously been described in simplistic
      terms, with the focus being solely on the behaviour itself and not on the
      individual's own positioning of their dyslexia or the social context associated
      with the act. There is an onus on all students with dyslexia to self-monitor how
      this aspect of their identity interacts with their professional duty of care. 

PMID- 25849236
TI  - Have OSCEs come of age in nursing education?
AB  - This article is intended to contribute to the current debate as to whether the
      objective structured clinical examination (OSCE) should become a standard
      assessment tool for undergraduate nursing education as they currently are for
      medicine. The authors describe how one UK university developed an OSCE for a
      nursing undergraduate programme with the aim of emphasising the need for nursing
      students to be competent in clinical skills and offering a means of standardising
      the assessment of these skills. There has been an increasing number of research
      studies carried out in this area at international level and this article's main
      contribution to the literature is the description of the Angoff standard-setting
      procedure that was used to calibrate the OSCE at this University and which makes
      it the first nursing OSCE in the UK to incorporate a scientific standard-setting
      procedure. 

PMID- 25849237
TI  - Examining the effect of patient-centred care on outcomes.
AB  - Within patient-centered care (PCC), the individual is viewed as an active member
      of the healthcare team. While there has been recent interest in conducting
      systematic reviews to examine the effectiveness of PCC interventions, various
      studies fall short in explaining the type of intervention most effective in
      producing significant changes to desired outcomes. The purpose of this systematic
      review was to determine the characteristics of PCC interventions that have
      demonstrated effectiveness in enhancing the quality of care and performance of
      self-care behaviours. A systematic review of 40 studies that addressed PCC
      interventions, included samples over the age of 18 years, and were published
      between 1995 and 2014 was performed. Descriptive statistics were used to
      delineate study, participant, and intervention characteristics. Results suggest
      PCC-based interventions are not effective when delivered to individuals living
      with chronic illnesses. 

PMID- 25849238
TI  - Binge drinking and cognitive impairment in young people.
AB  - AIMS AND OBJECTIVES: To investigate the links between the binge pattern of
      drinking and the development of cognitive impairment in young adults in the UK.
      To determine from the findings whether cognitive impairment is an additional
      public health concern manifesting from this form of alcohol misuse and its
      relevance to nursing practice. BACKGROUND: Young adults in the UK are
      participating in binge drinking; a 'harmful' form of alcohol misuse. Morbidity
      and mortality associated with alcohol misuse is already a public health concern.
      DESIGN: Literature review. METHOD: Multiple database searches were undertaken,
      which revealed three case-control studies. The studies all investigated the binge
      pattern of drinking as well as meeting the following inclusion criteria; primary
      research published from 2005 onwards, used a human sample, participants were aged
      18 to 24 and cognitive function was tested. RESULTS: The quantitative data found
      cognitive impairment present in young adult binge drinkers, specifically in
      regions of the frontal lobe, temporal lobe and hippocampus. Individually the
      studies did not pose strong enough evidence to generalise findings. However,
      collectively the core findings along with previous studies can validate the link
      between binge drinking and cognitive impairment. CONCLUSION: Nurse-led alcohol
      misuse screening and brief intervention is the most effective public health
      prevention strategy. It is important for nurses to keep abreast of current
      evidence to better inform their practice and the information they provide to
      their service users. This review emphasises the need for nurses to routinely
      screen young adults and address the associated risk to cognitive function when
      participating in harmful drinking.

PMID- 25849239
TI  - Duty to warn of risks moves to a prudent patient approach.
AB  - The United Kingdom Supreme Court has ruled that nurses, and other health
      professionals, can no longer paternalistically decide what information about the
      risks inherent in treatment should be disclosed to patients when obtaining
      consent ( Montgomery v Lanarkshire Health Board [2015] ). Patients must instead
      be given sufficient information about material risks to enable them to make an
      informed decision about whether to accept or refuse treatment. This article
      considers the impact of the Supreme Court ruling on nursing practice. 

PMID- 25849240
TI  - Relationships: from staff nurse to nurse consultant: Part 3: teamwork.

PMID- 25849241
TI  - Reliance on technology and the future of dialysis.
AB  - Emma Blakey discusses her experience of working on a dialysis unit, how strange
      it felt to be so reliant on machines and how important it is to be aware of
      national policy debates. 

PMID- 25849242
TI  - The future education of nurses and healthcare assistants.

PMID- 25849243
TI  - Applying the lessons of the Francis Inquiries: Culture Change, part two.
AB  - In this second part of his two-part column John Tingle continues his discussion
      of the Department of Health's progress report on applying the lessons learned
      from the tragic events at Mid Staffordshire NHS Foundation Trust. 

PMID- 25849244
TI  - Building resilience in ward leaders with Restorative Supervision.

PMID- 25849246
TI  - Regulation of transcriptionally active genes via the catalytically inactive Cas9
      in C. elegans and D. rerio.

PMID- 25849245
TI  - Association between variants in the interferon lambda 4 locus and substitutions
      in the hepatitis C virus non-structural protein 5A.
AB  - BACKGROUND & AIMS: Single nucleotide polymorphisms within the interferon lambda 4
      (IFNL4) locus are strongly associated with spontaneous clearance of hepatitis C
      virus (HCV) infection and early viral response to interferon therapy. Interaction
      between host genotype and amino acid substitutions might also influence the risk
      of antiviral resistance in interferon-free direct acting antiviral (DAA)
      therapies. METHODS: The relationship between IFNL4 genotype and HCV substitutions
      was analyzed in 929 patients with chronic HCV genotype 1b infection. Ultra-deep
      sequencing and quasispecies reconstruction was performed on the N-terminal region
      of NS5A in 57 patients. RESULTS: IFNL4 genotype was strongly associated with HCV
      NS5A Y93 and core protein substitutions, and the number and diversity of
      predicted quasispecies was marginally greater in IFNL4 TT/TT patients compared to
      TT/DeltaG, DeltaG/DeltaG patients. RNA secondary structure prediction of the NS5A
      region suggests that variable sites are more likely to occupy unpaired, high
      entropy positions. CONCLUSIONS: HCV infection is proposed to induce a more
      efficient antiviral response in individuals with the IFNL4 TT/TT genotype that
      results either in viral clearance or selection for viral adaptations. The
      association between IFNL4 TT/TT genotype and Y93 substitutions may impact the
      risk of antiviral resistance in NS5A inhibitors in DAA therapy.

PMID- 25849247
TI  - Shed NKG2D ligand boosts NK cell immunity.
AB  - Ligands for natural killer (NK) cell activating receptors can be released from
      tumor cells and are believed to promote tumor growth by acting as decoys for
      effector lymphocytes. In a recent paper published in Science, Deng et al. report
      another scenario in which a shed form of the MULT1 mouse NKG2D ligand boosts NK
      cell functions. 

PMID- 25849248
TI  - Intron targeting-mediated and endogenous gene integrity-maintaining knockin in
      zebrafish using the CRISPR/Cas9 system.

PMID- 25849249
TI  - CD146: the unveiling of a pro-angiogenic netrin receptor.
AB  - Netrin-1, a classic neuronal guidance cue, can promote angiogenesis under certain
      developmental and pathological conditions, but key receptors on vascular
      endothelium have remained elusive. A recent study published in Cell Research by
      Tu et al. reveals that CD146, an endothelial receptor of the immunoglobulin
      superfamily, binds netrin-1 with high affinity and may play an important role in
      regulating angiogenesis. 

PMID- 25849250
TI  - Protein composition of the outermost exosporium-like layer of Clostridium
      difficile 630 spores.
AB  - Clostridium difficile spores are considered the morphotype of infection,
      transmission and persistence of C. difficile infections. There is a lack of
      information on the composition of the outermost exosporium layer of C. difficile
      spores. Using recently developed exosporium removal methods combined with MS/MS,
      we have established a gel-free approach to analyze the proteome of the exosporium
      of C. difficile spores of strain 630. A total of 184 proteins were found in the
      exosporium layer of C. difficile spores. We identified 7 characterized spore coat
      and/or exosporium proteins; 6 proteins likely to be involved in spore resistance;
      6 proteins possibly involved in pathogenicity; 13 uncharacterized proteins; and
      146 cytosolic proteins that might have been encased into the exosporium during
      assembly, similarly as reported for Bacillus anthracis and Bacillus cereus
      spores. We demonstrate through Flag-fusions that CotA and CotB are mainly located
      in the spore coat, while the exosporium collagen-like glycoproteins (i.e. BclA1,
      BclA2 and BclA3), the exosporium morphogenetic proteins CdeC and CdeM, and the
      uncharacterized exosporium proteins CdeA and CdeB are mainly located in the
      exosporium layer of C. difficile 630 spores. This study offers novel candidates
      of C. difficile exosporium proteins as suitable targets for detection, removal
      and spore-based therapies. BIOLOGICAL SIGNIFICANCE: This study offers a novel
      strategy to identify proteins of the exosporium layer of C. difficile spores and
      complements previous proteomic studies on the entire C. difficile spores and
      spore coat since it defines the proteome of the outermost layer of C. difficile
      spores, the exosporium. This study suggests that C. difficile spores have several
      proteins involved in protection against environmental stress as well as putative
      virulence factors that might play a role during infection. Spore exosporium
      structural proteins were also identified providing the ground basis for further
      functional studies of these proteins. Overall this work provides new protein
      target for the diagnosis and/or therapeutics that may contribute to combat C.
      difficile infections.

PMID- 25849251
TI  - Transcriptomic and proteomic analyses of splenic immune mechanisms of rainbow
      trout (Oncorhynchus mykiss) infected by Aeromonas salmonicida subsp. salmonicida.
AB  - Furunculosis caused by Aeromonas salmonicida subsp. salmonicida is an epidemic
      disease among salmonids, including rainbow trout (Oncorhynchus mykiss). However,
      the immune mechanisms that are elicited in rainbow trout against the invasion of
      A. salmonicida are not yet fully understood. In this study, we examined the
      spleen to investigate the immune response of rainbow trout at 3days post
      infection by A. salmonicida at the transcriptome and proteome levels by using
      Illumina-seq and iTRAQ methods, respectively. A total of 1036 genes and 133
      proteins were found to undergo differential expression during the immune response
      of the spleen against A. salmonicida infection. Gene ontology and KEGG analysis
      were conducted among the differentially expressed genes and proteins, revealing
      that immune system process and response to stimulus were the top two biological
      processes, and immune system, signaling molecules and interaction, and immune
      diseases were the differential pathways activated. Correlation analysis of
      transcriptomic and proteomic results showed 17 proteins (11 upregulated and 6
      downregulated) having consistent expression at RNA and protein levels. Moreover,
      protein-protein interaction analysis showed that diseases, proteasome, aminoacyl
      tRNA biosynthesis, and nucleotide metabolism were the main interactions among the
      consistently expressed proteins. Consequently, these upregulated proteins,
      namely, ferritin, CD209, IL13Ralpha1, VDAC2, GIMAP7, PSMA1, and two ANXA11s could
      be considered as potential biomarkers for rainbow trout immune responses.
      BIOLOGICAL SIGNIFICANCE: This study provides the first identification of immune
      markers through an analysis of the differential expression of both genes and
      their corresponding protein products in the spleen of rainbow trout after
      infection by A. salmonicida, shedding light on the molecular mechanisms triggered
      in rainbow trout against A. salmonicida infection and providing new molecular
      targets for further immunological research in fish.

PMID- 25849252
TI  - A comparative proteome analysis reveals flagellin, chemotaxis regulated proteins
      and amylovoran to be involved in virulence differences between Erwinia amylovora
      strains.
AB  - Erwinia amylovora is a Gram-negative bacterium that causes the destructive
      disease fire blight affecting most members of the Rosaceae family, of which apple
      and pear are economically the most important hosts. E. amylovora has been
      considered as a homogeneous species in whole, although significant differences in
      virulence patterns have been observed. However, the underlying causes of the
      differences in virulence remain to be discovered. In a first-time comparative
      proteomic approach using E. amylovora, 2D differential in-gel electrophoresis
      (DIGE) was used to identify proteins that could explain the gradual difference in
      virulence between four different strains. Two important proteins were identified,
      FliC and CheY, both involved in flagella structure, motility and chemotaxis,
      which were more abundant in the least virulent strain. In the highly virulent
      strains the protein GalF, involved in amylovoran production, was more abundant,
      which was consistent with the higher expression of the gene and the higher
      amylovoran content in this strain in vitro. Together, these results confirm the
      involvement of amylovoran in virulence, but also imply an indirect role of
      flagellin in virulence as elicitor of plant defence. BIOLOGICAL SIGNIFICANCE:
      This research provides new insights into our current understanding of the
      virulence of Erwinia amylovora. This plant-pathogen is considered a homogeneous
      species although different strains show differences in virulence. Despite the
      efforts made on the genomic level which resulted in the discovery of virulence
      factors, the reason for the different virulence patterns between strains has not
      yet been identified. In our lab we used a comparative proteomic approach, which
      has never been published before, to identify proteins involved in these
      differences between strains and hereby possibly involved in virulence. Our
      results provide interesting insights in virulence and present us with the
      opportunity to glance into the proteome of E. amylovora.

PMID- 25849253
TI  - Production of cellobionate from cellulose using an engineered Neurospora crassa
      strain with laccase and redox mediator addition.
AB  - We report a novel production process for cellobionic acid from cellulose using an
      engineered fungal strain with the exogenous addition of laccase and a redox
      mediator. A previously engineered strain of Neurospora crassa (F5?ace-1?cre
      1?ndvB) was shown to produce cellobionate directly from cellulose without the
      addition of exogenous cellulases. Specifically, N. crassa produces cellulases,
      which hydrolyze cellulose to cellobiose, and cellobiose dehydrogenase (CDH),
      which oxidizes cellobiose to cellobionate. However, the conversion of cellobiose
      to cellobionate is limited by the slow re-oxidation of CDH by molecular oxygen.
      By adding low concentrations of laccase and a redox mediator to the fermentation,
      CDH can be efficiently oxidized by the redox mediator, with in-situ re-oxidation
      of the redox mediator by laccase. The conversion of cellulose to cellobionate was
      optimized by evaluating pH, buffer, and laccase and redox mediator addition time
      on the yield of cellobionate. Mass and material balances were performed, and the
      use of the native N. crassa laccase in such a conversion system was evaluated
      against the exogenous Pleurotus ostreatus laccase. This paper describes a working
      concept of cellobionate production from cellulose using the CDH-ATBS-laccase
      system in a fermentation system. 

PMID- 25849254
TI  - GRECCAR 8: impact on survival of the primary tumor resection in rectal cancer
      with unresectable synchronous metastasis: a randomized multicentre study.
AB  - BACKGROUND: A majority of patients with rectal cancer and metastasis are not
      eligible to curative treatment because of an extensive and unresectable
      metastatic disease. Primary tumor resection is still debated in this situation.
      Rectal surgery treats or prevents the symptoms and avoids the risk of acute
      complications related to the primary tumor. Several studies on colorectal cancers
      seem to show interesting results in terms of survival in favor to the resection
      of the primary tumor. To date, no randomized trial or even a prospective study
      has assessed the impact of primary tumor resection on overall survival in
      patients with colorectal cancer with unresectable metastasis. All published
      studies were retrospective and included colon and rectal cancers. Rectal cancer
      is associated with specific problems related to the rectal surgery. Surgery is
      more complex, and may be source of more morbidity and postoperative functional
      dysfunctions (stoma, digestive, sexual, urinary) than colic surgery. On the other
      hand, symptoms related to the progression of rectal tumor are often very
      disabling: pain, rectal syndrome. METHODS/DESIGN: GRECCAR 8 is a multicentre
      randomized open-label controlled trial aimed to evaluate the impact on survival
      of the primary tumor resection in rectal cancer with unresectable synchronous
      metastasis. Patients must undergo upfront systemic chemotherapy for at least 4
      courses before inclusion. Patients with progressive metastatic disease during
      upfront chemotherapy will be excluded from the study. Patients will be randomly
      assigned in a 1:1 ratio to Arm A: primary tumor resection followed by systemic
      chemotherapy versus Arm B: systemic chemotherapy alone. Primary endpoint will be
      overall survival measured from the date of randomization to the date of death or
      to the end of follow-up (2 years). Secondary endpoints will include progression
      free survival, quality of life, toxicity of chemotherapy, response of the primary
      tumor and metastatic disease to chemotherapy, postoperative morbidity and
      mortality, rate of patient not eligible for postoperative chemotherapy (arm A),
      primary tumor related complications and rate of emergency surgery (arm B). The
      number of patients needed is 290. TRIAL REGISTRATION: ClinicalTrial.gov:
      NCT02314182.

PMID- 25849255
TI  - N-Terminal Modification with Pseudo-Bifunctional PEG-Hexadecane Markedly Improves
      the Pharmacological Profile of Human Growth Hormone.
AB  - Human growth hormone (hGH) has been used to treat children with short stature,
      renal failure, and Turner's syndrome. However, clinical application of hGH
      suffers from its short plasma half-life and low bioavailability. PEGylation and
      albumin binding are two of the most effective approaches to prolong the plasma
      half-life of hGH. However, the steric shielding effects of polyethylene glycol
      (PEG) and albumin can drastically decrease the bioactivity of hGH, which is
      opposite to the increased pharmacokinetics (PK). In the present study, a long
      acting hGH with markedly improved pharmacological profile was rationally designed
      and prepared by N-terminal modification of hGH with pseudo-bifunctional PEG
      hexadecane by using PEG (3.5 kDa or 10 kDa) as the linker. PEGylation and albumin
      binding with hexadecane can increase the hydrodynamic volume and decrease the
      immunogenicity of hGH, which thereby markedly increases the PK of hGH. Since N
      terminus is far from the bioactive domain of hGH, N-terminal modification of hGH
      can minimize the steric shielding effects on the bioactive domain of hGH.
      Hexadecane-bound albumin can be slowly released from hGH during the in vivo
      circulation, which can slowly restore the bioactivity of hGH. Thus, the high
      bioactivity of PEG-hexadecane modified hGH (hGH-PEG-HD) was synergistically
      achieved by N-terminal modification with pseudo-bifunctional PEG-hexadecane and
      slow-release of albumin. The high pharmacodynamics (PD) of hGH-PEG-HD was due to
      the synergistic effect of the high bioactivity and the overall increased PK. 

PMID- 25849256
TI  - Fullerene up-take alters bilayer structure and elasticity: A small angle X-ray
      study.
AB  - The coupling of fullerene (C60) to the structure and elasticity of 1-palmitoyl-2
      oleoyl-sn-glycero-3-phosphocholine bilayers has been explored by synchrotron
      small angle X-ray scattering. Multilamellar vesicles were loaded with 0, 2 and 10
      mol.% of C60 and studied in a temperature range from 15 to 65  degrees C. The
      addition of C60 caused an increase in the bilayer undulations (~ 20%), in the
      bilayer separation (~ 15%), in the linear expansion coefficient and caused a drop
      in the bending rigidity of the bilayers (20-40%). Possible damaging effects of
      fullerene on biomembranes are mainly discussed on the basis of altered bilayer
      fluidity and elasticity changes.

PMID- 25849258
TI  - Structural control of nonadiabatic bond formation: the photochemical formation
      and stability of substituted 4a,4b-dihydrotriphenylenes.
AB  - Nonadiabatic photocyclization makes bonds and is the first step in the
      photoinduced cyclodehydrogenation of ortho-arenes to yield polycyclic aromatic
      hydrocarbons. How molecular structure alters potential-energy landscapes, excited
      state dynamics, and stabilities of reactants and intermediates underlies the
      feasibility of desirable photochemistry. In order to gain insight into these
      structure-dynamics relationships, we have used femtosecond transient absorption
      spectroscopy (TAS) to examine photoinduced dynamics of 1,2,3-triphenylbenzene
      (TPB) and ortho-quaterphenyl (OQTP), phenyl-subsituted analogues of ortho
      terphenyl (OTP). Dynamics of TPB and OTP are quite similar: TPB exhibits fast
      (7.4 ps) excited-state decay with concomitant formation and vibrational
      relaxation of 9-phenyl-dihydrotriphenylene (9-phenyl DHT). In contrast,
      photoexcited OQTP exhibits multistate kinetics leading to formation of 1-phenyl
      DHT. Excited-state calculations reveal the existence of two distinct minima on
      the OQTP S1 surface and, together with photophysical data, support a mechanism
      involving both direct cyclization by way of an asymmetric structure and indirect
      cyclization by way of a symmetric quinoid-like minimum. Temperature-dependent
      nanosecond TAS was utilized to assess the relative stabilities of intermediates,
      substantiating the observed trend in photochemical reactivity OTP > OQTP > TPB.
      In total, this work demonstrates how specific structural variations alter the
      course of the excited-state dynamics and photoproduct stability that underlies
      desired photochemistry. 

PMID- 25849257
TI  - Machine learning assisted design of highly active peptides for drug discovery.
AB  - The discovery of peptides possessing high biological activity is very challenging
      due to the enormous diversity for which only a minority have the desired
      properties. To lower cost and reduce the time to obtain promising peptides,
      machine learning approaches can greatly assist in the process and even partly
      replace expensive laboratory experiments by learning a predictor with existing
      data or with a smaller amount of data generation. Unfortunately, once the model
      is learned, selecting peptides having the greatest predicted bioactivity often
      requires a prohibitive amount of computational time. For this combinatorial
      problem, heuristics and stochastic optimization methods are not guaranteed to
      find adequate solutions. We focused on recent advances in kernel methods and
      machine learning to learn a predictive model with proven success. For this type
      of model, we propose an efficient algorithm based on graph theory, that is
      guaranteed to find the peptides for which the model predicts maximal bioactivity.
      We also present a second algorithm capable of sorting the peptides of maximal
      bioactivity. Extensive analyses demonstrate how these algorithms can be part of
      an iterative combinatorial chemistry procedure to speed up the discovery and the
      validation of peptide leads. Moreover, the proposed approach does not require the
      use of known ligands for the target protein since it can leverage recent multi
      target machine learning predictors where ligands for similar targets can serve as
      initial training data. Finally, we validated the proposed approach in vitro with
      the discovery of new cationic antimicrobial peptides. Source code freely
      available at http://graal.ift.ulaval.ca/peptide-design/. 

PMID- 25849260
TI  - Germline editing: time for discussion.

PMID- 25849259
TI  - Familiality of mood repair responses among youth with and without histories of
      depression.
AB  - Affect regulation skills develop in the context of the family environment,
      wherein youths are influenced by their parents', and possibly their siblings',
      regulatory responses and styles. Regulatory responses to sadness (mood repair)
      that exacerbate or prolong dysphoria (maladaptive mood repair) may represent one
      way in which depression is transmitted within families. We examined self-reported
      adaptive and maladaptive mood repair responses across cognitive, social and
      behavioural domains in Hungarian 11- to 19-year-old youth and their parents.
      Offspring included 214 probands with a history of childhood-onset depressive
      disorder, 200 never depressed siblings and 161 control peers. Probands reported
      the most problematic mood repair responses, with siblings reporting more modest
      differences from controls. Mood repair responses of parents and their offspring,
      as well as within sib-pairs, were related, although results differed as a
      function of the regulatory response domain. Results demonstrate familiality of
      maladaptive and adaptive mood repair responses in multiple samples. These
      familial associations suggest that relationships with parents and siblings within
      families may impact the development of affect regulation in youth. 

PMID- 25849261
TI  - Reexamination casts doubt on brain tissue classified as healthy.

PMID- 25849262
TI  - After flu vaccine mismatch, calls for delayed selection intensify.

PMID- 25849263
TI  - Warren joins lawmakers proposing new ideas for science funding.

PMID- 25849264
TI  - Questions raised about whether compulsory licenses get best prices.

PMID- 25849265
TI  - New model tackles sticky problem of getting drugs past mucus.

PMID- 25849267
TI  - Many returns: call-ins and breakfasts hand back results to study volunteers.

PMID- 25849268
TI  - A mediator for malaria stickiness in A versus O blood.

PMID- 25849269
TI  - Harnessing gene repression to inhibit leukemia.

PMID- 25849270
TI  - Beta cell glutamate receptor antagonists: novel oral antidiabetic drugs?

PMID- 25849272
TI  - Erratum: a next-generation dual-recombinase system for time- and host-specific
      targeting of pancreatic cancer.

PMID- 25849271
TI  - Intracellular chloride accumulation: a possible mechanism for cognitive deficits
      in Down syndrome.

PMID- 25849273
TI  - Corrigendum: Translation from a DMD exon 5 IRES results in a functional
      dystrophin isoform that attenuates dystrophinopathy in humans and mice.

PMID- 25849274
TI  - Corrigendum: Inhibition of JAK-STAT signaling stimulates adult satellite cell
      function.

PMID- 25849275
TI  - Corrigendum: Asfotase-alpha improves bone growth, mineralization and strength in
      mouse models of neurofibromatosis type-1.

PMID- 25849276
TI  - Erratum: De novo fatty acid synthesis controls the fate between regulatory T and
      T helper 17 cells.

PMID- 25849278
TI  - On the treewidths of graphs of bounded degree.
AB  - In this paper, we develop a new technique to study the treewidth of graphs with
      bounded degree. We show that the treewidth of a graph G = (V, E) with maximum
      vertex degree d is at most [Formula: see text] for sufficiently large d, where C
      is a constant. 

PMID- 25849277
TI  - Symportin 1 chaperones 5S RNP assembly during ribosome biogenesis by occupying an
      essential rRNA-binding site.
AB  - During 60S biogenesis, mature 5S RNP consisting of 5S RNA, RpL5 and RpL11,
      assembles into a pre-60S particle, where docking relies on RpL11 interacting with
      helix 84 (H84) of the 25S RNA. How 5S RNP is assembled for recruitment into the
      pre-60S is not known. Here we report the crystal structure of a ternary symportin
      Syo1-RpL5-N-RpL11 complex and provide biochemical and structural insights into 5S
      RNP assembly. Syo1 guards the 25S RNA-binding surface on RpL11 and competes with
      H84 for binding. Pull-down experiments show that H84 releases RpL11 from the
      ternary complex, but not in the presence of 5S RNA. Crosslinking mass
      spectrometry visualizes structural rearrangements on incorporation of 5S RNA into
      the Syo1-RpL5-RpL11 complex supporting the formation of a pre-5S RNP. Our data
      underline the dual role of Syo1 in ribosomal protein transport and as an assembly
      platform for 5S RNP. 

PMID- 25849279
TI  - Divergent, stereoselective access to heterocyclic alpha,alpha-quaternary- and
      beta(2,3,3)-amino acid derivatives from a N-Pmp-protected Orn-derived beta
      lactam.
AB  - A suitably protected Orn-derived (3S,4S)-beta-lactam was used as common
      intermediate in the synthesis of conformationally constrained (3S,4S)-2
      oxoazepane alpha,alpha- and (2S,3S)-2-oxopiperidine-beta(2,3,3)-amino acid
      derivatives. Compared to alternative procedures using an N-p-methoxybenzyl group
      at the 2-azetidinone, the incorporation of a p-methoxyphenyl moiety is crucial
      for the excellent stereochemical outcomes in the preparation of these
      heterocyclic amino acids. Chemoselective 7- or 6-exo-trig cyclization was
      achieved through alternative sequences of Pmp-deprotection/Boc-activation,
      followed by inter- and intramolecular beta-lactam ring opening, respectively. 

PMID- 25849280
TI  - Correction: Validation of reference housekeeping genes for gene expression
      studies in western corn rootworm (Diabrotica virgifera virgifera).

PMID- 25849281
TI  - Cognition and mood-related behaviors in L3mbtl1 null mutant mice.
AB  - Alterations in histone lysine methylation and epigenetic regulators of gene
      expression could play a role in the neurobiology and treatment of patients
      diagnosed with mood spectrum disorder, including depression and anxiety.
      Mutations and altered expression of various lysine methyltransferases (KMTs) and
      demethylases (KDMs) have been linked to changes in motivational and emotional
      behaviors in preclinical model systems. However, it is not known whether
      regulators operating downstream of histone lysine methylation could affect mood
      related behavior. Malignant Brain Tumor (MBT) domain 'chromatin reader' proteins
      bind to methylated histone lysine residues and associate with chromatin
      remodeling complexes to facilitate or repress gene expression. MBT proteins,
      including the founding member, L3mbtl1, maintain high levels of expression in
      neurons of the mature brain. Here, we exposed L3mbtl1 null mutant mice to a wide
      range of tests exploring cognition and mood-relevant behaviors at baseline and in
      the context of social isolation, as a stressor to elicit depression-related
      behavior in susceptible mice. L3mbtl1 loss-of-function was associated with
      significant decreases in depression and and anxiety in some of the behavioral
      paradigms. This was not associated with a more generalized neurological
      dysfunction because cognition and memory remained unaltered in comparison to
      controls. These findings warrant further investigations on the role of MBT
      chromatin reader proteins in the context of emotional and affective behaviors. 

PMID- 25849283
TI  - A new casbane diterpene from Euphorbia pekinensis.
AB  - A new casbane diterpenoid, referred to as pekinenin G, together with one cembrane
      diterpene and four known casbane diterpenoids were isolated from the roots of
      Euphorbia pekinensis. Their structures were elucidated on the basis of
      spectroscopic studies and comparison with related known compounds. The six
      compounds showed different cytotoxic activities against four human cancer cell
      lines. 

PMID- 25849282
TI  - Comprehensive profiling of amino acid response uncovers unique methionine
      deprived response dependent on intact creatine biosynthesis.
AB  - Besides being building blocks for protein synthesis, amino acids serve a wide
      variety of cellular functions, including acting as metabolic intermediates for
      ATP generation and for redox homeostasis. Upon amino acid deprivation, free
      uncharged tRNAs trigger GCN2-ATF4 to mediate the well-characterized
      transcriptional amino acid response (AAR). However, it is not clear whether the
      deprivation of different individual amino acids triggers identical or distinct
      AARs. Here, we characterized the global transcriptional response upon deprivation
      of one amino acid at a time. With the exception of glycine, which was not
      required for the proliferation of MCF7 cells, we found that the deprivation of
      most amino acids triggered a shared transcriptional response that included the
      activation of ATF4, p53 and TXNIP. However, there was also significant
      heterogeneity among different individual AARs. The most dramatic transcriptional
      response was triggered by methionine deprivation, which activated an extensive
      and unique response in different cell types. We uncovered that the specific
      methionine-deprived transcriptional response required creatine biosynthesis. This
      dependency on creatine biosynthesis was caused by the consumption of S-Adenosyl-L
      methionine (SAM) during creatine biosynthesis that helps to deplete SAM under
      methionine deprivation and reduces histone methylations. As such, the
      simultaneous deprivation of methionine and sources of creatine biosynthesis
      (either arginine or glycine) abolished the reduction of histone methylation and
      the methionine-specific transcriptional response. Arginine-derived ornithine was
      also required for the complete induction of the methionine-deprived specific gene
      response. Collectively, our data identify a previously unknown set of
      heterogeneous amino acid responses and reveal a distinct methionine-deprived
      transcriptional response that results from the crosstalk of arginine, glycine and
      methionine metabolism via arginine/glycine-dependent creatine biosynthesis. 

PMID- 25849285
TI  - Morphogens Reveal the Appearance and Functions of lncRNAs.
AB  - During the first meiotic division, the entire genetic information from DNA is
      transcribed into mRNPs and stored in the ovoplasm in the form of mRNP particles.
      The 39 human nuclear HOX proteins bind to thousands of mRNAs transcribed
      repeatedly by lampbrush chromosomes. HOX proteins suppress processing and
      translation. The RNP particles containing lncRNAs+HOX proteins are the morphogens
      ("transcription factors," more precisely differentiation factors), which unlock
      new genes and differentiate the cells of the developing embryo. All ovoplasmic
      mRNAs bound with HOX proteins do not translate and are noncoding. Their
      destination (purpose) is transportation of HOX proteins to the complementary DNAs
      and cell differentiation. 

PMID- 25849284
TI  - Depletion of the polyamines spermidine and spermine by overexpression of
      spermidine/spermine N1-acetyltransferase 1 (SAT1) leads to mitochondria-mediated
      apoptosis in mammalian cells.
AB  - The polyamines putrescine, spermidine and spermine are intimately involved in the
      regulation of cellular growth and viability. Transduction of human embryonic
      kidney (HEK) 293T cells with an adenovirus encoding a key polyamine catabolic
      enzyme, spermidine N1-acetyltransferase 1 (SSAT1)/SAT1 (AdSAT1), leads to a rapid
      depletion of spermidine and spermine, arrest in cell growth and a decline in cell
      viability. Annexin V/propidium iodide FACS analyses, terminal uridine nucleotide
      end-labelling (TUNEL) and caspase 3 assays showed a clear indication of apoptosis
      in AdSAT1-transduced cells (at 24-72 h), but not in cells transduced with GFP
      encoding adenovirus (AdGFP). Apoptosis in the polyamine-depleted cells occurs by
      the mitochondrial intrinsic pathway, as evidenced by loss of mitochondrial
      membrane potential, increase in pro-apoptotic Bax, decrease in anti-apoptotic Bcl
      xl, Bcl2 and Mcl-1 and release of cytochrome c from mitochondria, upon
      transduction with AdSAT1. Moreover, TEM images of AdSAT1-transduced cells
      revealed morphological changes commonly associated with apoptosis, including cell
      shrinkage, nuclear fragmentation, mitochondrial alteration, vacuolization and
      membrane blebbing. The apoptosis appears to result largely from depletion of the
      polyamines spermidine and spermine, as the polyamine analogues alpha
      methylspermidine (alpha-MeSpd) and N1,N12-dimethylspermine (Me2Spm) that are not
      substrates for SAT1 could partially restore growth and prevent apoptosis of
      AdSAT1-transduced cells. Inhibition of polyamine oxidases did not restore the
      growth of AdSAT1-transduced cells or block apoptosis, suggesting that the growth
      arrest and apoptosis were not induced by oxidative stress resulting from
      accelerated polyamine catabolism. Taken together, these data provide strong
      evidence that the depletion of the polyamines spermidine and spermine leads to
      mitochondria-mediated apoptosis.

PMID- 25849287
TI  - In situ imaging of on-surface, solvent-free molecular single-crystal growth.
AB  - The formation of crystalline materials has been studied for more than a century.
      Recent discoveries about the self-assembly of many inorganic materials, involving
      aggregation of nanoparticle (NP) precursors or pre-nucleation clusters, challenge
      the simple assumptions of classical crystallization theory. The situation for
      organic materials is even more of a terra incognita due to their high complexity.
      Using in situ high-temperature atomic force microscopy during the solvent-free
      crystallization of an organic compound [Ni(quinolone-8-thiolate)2], we observe
      long-range migration of NPs on a silica substrate and their incorporation into
      larger crystals, suggesting a non-classical pathway in the growth of the
      molecular crystal. 

PMID- 25849286
TI  - delta-tocotrienol induces human bladder cancer cell growth arrest, apoptosis and
      chemosensitization through inhibition of STAT3 pathway.
AB  - Vitamin E intake has been implicated in reduction of bladder cancer risk.
      However, the mechanisms remain elusive. Here we reported that delta-tocotrienol
      (delta-T3), one of vitamin E isomers, possessed the most potent cytotoxic
      capacity against human bladder cancer cells, compared with other Vitamin E
      isomers. delta-T3 inhibited cancer cell proliferation and colonogenicity through
      induction of G1 phase arrest and apoptosis. Western blotting assay revealed that
      delta-T3 increased the expression levels of cell cycle inhibitors (p21, p27), pro
      apoptotic protein (Bax) and suppressed expression levels of cell cycle protein
      (Cyclin D1), anti-apoptotic proteins (Bcl-2, Bcl-xL and Mcl-1), resulting in the
      Caspase-3 activation and cleavage of PARP. Moreover, the delta-T3 treatment
      inhibited ETK phosphorylation level and induced SHP-1 expression, which was
      correlated with downregulation of STAT3 activation. In line with this, delta-T3
      reduced the STAT3 protein level in nuclear fraction, as well as its transcription
      activity. Knockdown of SHP-1 partially reversed delta-T3-induced cell growth
      arrest. Importantly, low dose of delta-T3 sensitized Gemcitabine-induced
      cytotoxic effects on human bladder cancer cells. Overall, our findings
      demonstrated, for the first time, the cytotoxic effects of delta-T3 on bladder
      cancer cells and suggest that delta-T3 might be a promising chemosensitization
      reagent for Gemcitabine in bladder cancer treatment. 

PMID- 25849289
TI  - Contribution of Leg-Muscle Forces to Paddle Force and Kayak Speed During Maximal
      Effort Flat-Water Paddling.
AB  - The purpose was to investigate the contribution of leg-muscle-generated forces to
      paddle force and kayak speed during maximal-effort flat-water paddling. Five
      elite male kayakers at national and international level participated. The
      participants warmed up at progressively increasing speeds and then performed a
      maximal-effort, nonrestricted paddling sequence. This was followed after 5 min
      rest by a maximal-effort paddling sequence with the leg action restricted--the
      knee joints "locked." Left- and right-side foot-bar and paddle forces were
      recorded with specially designed force devices. In addition, knee angular
      displacement of the right and left knees was recorded with electrogoniometric
      technique, and the kayak speed was calculated from GPS signals sampled at 5 Hz.
      The results showed that reduction in both push and pull foot-bar forces resulted
      in a reduction of 21% and 16% in mean paddle-stroke force and mean kayak speed,
      respectively. Thus, the contribution of foot-bar force from lower-limb action
      significantly contributes to kayakers' paddling performance.

PMID- 25849288
TI  - Comparative study of the protein profiles of Sunki mandarin and Rangpur lime
      plants in response to water deficit.
AB  - BACKGROUND: Rootstocks play a major role in the tolerance of citrus plants to
      water deficit by controlling and adjusting the water supply to meet the
      transpiration demand of the shoots. Alterations in protein abundance in citrus
      roots are crucial for plant adaptation to water deficit. We performed two
      dimensional electrophoresis (2-DE) separation followed by LC/MS/MS to assess the
      proteome responses of the roots of two citrus rootstocks, Rangpur lime (Citrus
      limonia Osbeck) and 'Sunki Maravilha' (Citrus sunki) mandarin, which show
      contrasting tolerances to water deficits at the physiological and molecular
      levels. RESULTS: Changes in the abundance of 36 and 38 proteins in Rangpur lime
      and 'Sunki Maravilha' mandarin, respectively, were observed via LC/MS/MS in
      response to water deficit. Multivariate principal component analysis (PCA) of the
      data revealed major changes in the protein profile of 'Sunki Maravilha' in
      response to water deficit. Additionally, proteomics and systems biology analyses
      allowed for the general elucidation of the major mechanisms associated with the
      differential responses to water deficit of both varieties. The defense mechanisms
      of Rangpur lime included changes in the metabolism of carbohydrates and amino
      acids as well as in the activation of reactive oxygen species (ROS)
      detoxification and in the levels of proteins involved in water stress defense. In
      contrast, the adaptation of 'Sunki Maravilha' to stress was aided by the
      activation of DNA repair and processing proteins. CONCLUSIONS: Our study reveals
      that the levels of a number of proteins involved in various cellular pathways are
      affected during water deficit in the roots of citrus plants. The results show
      that acclimatization to water deficit involves specific responses in Rangpur lime
      and 'Sunki Maravilha' mandarin. This study provides insights into the effects of
      drought on the abundance of proteins in the roots of two varieties of citrus
      rootstocks. In addition, this work allows for a better understanding of the
      molecular basis of the response to water deficit in citrus. Further analysis is
      needed to elucidate the behaviors of the key target proteins involved in this
      response.

PMID- 25849290
TI  - Inhibition of protein kinase C enhances angiogenesis induced by platelet-derived
      growth factor C in hyperglycemic endothelial cells.
AB  - BACKGROUND: Diabetes is a risk factor for the development of cardiovascular
      diseases with impaired angiogenesis. We have previously shown that platelet
      derived growth factor C (PDGF-C) and its receptor, PDGF receptor alpha (PDGFR
      alpha) were downregulated in ischemic limbs of diabetic mice, although the
      underlying mechanisms remained elusive. Protein kinase C (PKC) is a family of
      serine/threonine kinases and is known to be involved in angiogenesis. The purpose
      of this study is to elucidate the mechanisms of how PDGF-C/PDGFR-alpha axis is
      impaired in diabetes. METHODS: Human umbilical vein endothelial cells (HUVECs)
      and human cardiac microvascular endothelial cells (HMVECs) cultured in
      normoglycemic or hyperglycemic conditions were examined. We also examined the
      effects of PKC inhibition on the PDGF-C/PDGFR-alpha axis in endothelial cells
      exposed to hyperglycemia. RESULTS: Hyperglycemia inhibited proliferation and
      decreased viability of both HUVECs and HMVECs. Hyperglycemic endothelial cells
      exhibited decreased PDGFR-alpha expression both at messenger RNA (mRNA) and
      protein levels, while there was no significant change in expression of PDGF-C. We
      also found that expression of PKC-alpha, one of the PKC isoforms, was increased
      in hyperglycemic endothelial cells and that inhibition of PKC upregulated PDGFR
      alpha expression in these cells. Phosphorylation of extracellular signal
      regulated kinase (ERK) and Akt induced by PDGF-C was significantly attenuated in
      hyperglycemic endothelial cells, whereas inhibition of PKC effectively reversed
      these inhibitory effects. Moreover, inhibition of PKC also promoted angiogenesis
      induced by PDGF-C in hyperglycemic endothelial cells, which was not observed in
      vascular endothelial growth factor-A (VEGF-A)-induced angiogenesis. CONCLUSIONS:
      These findings suggest that downregulation of the PDGF-C/PDGFR-alpha axis is
      involved in impaired angiogenesis of hyperglycemia through upregulation of PKC.
      Targeting PKC to restore PDGF-C signaling might be a novel therapeutic strategy
      for the treatment of vascular complications in diabetes.

PMID- 25849291
TI  - Iron impregnated activated carbon as an efficient adsorbent for the removal of
      methylene blue: regeneration and kinetics studies.
AB  - In this study, iron impregnated activated carbon (FeAC) was synthesized following
      an oxidation and iron impregnation of activated carbon (AC). Both the AC and FeAC
      were characterized by pHZPC and FTIR spectroscopy. The removal of Methylene Blue
      (MB) by AC and FeAC was examined under various experimental conditions. The FeAC
      showed up to 95% (higher than AC) MB removal in the pH range of 7-10. Although
      the reaction kinetics was pseudo-second order, the overall rate was controlled by
      a number of processes such as film diffusion, pore diffusion and intraparticle
      diffusion. The activation energy values for the MB uptake by AC and FeAC (21.79
      and 14.82 kJ/mol, respectively) revealed a physisorption process. In the
      regeneration study, FeAC has shown consistently >= 90% MB removal even up to 10
      repeated cycles. The reusable characteristic of the spent FeAC improved the
      practical use of activated carbon and can be a breakthrough for continuous flow
      system applications where it can work effectively without any significant
      reduction in its performance. 

PMID- 25849292
TI  - Biosynthesis and role of 3-methylbutanal in cheese by lactic acid bacteria: Major
      metabolic pathways, enzymes involved, and strategies for control.
AB  - Branched chain aldehyde, 3-methylbutanal is associated as a key flavor compound
      with many hard and semi-hard cheese varieties. The presence and impact of this
      flavor compound in bread, meat, and certain beverages has been recently
      documented, however its presence and consequences regarding cheese flavor were
      not clearly reported. This paper gives an overview of the role of 3-methylbutanal
      in cheese, along with the major metabolic pathways and key enzymes leading to its
      formation. Moreover, different strategies are highlighted for the control of this
      particular flavor compound in specific cheese types.

PMID- 25849293
TI  - The use of autologous fascia lata graft in the laparoscopic reinforcement of
      large hiatal defect: initial observations of the surgical technique.
AB  - BACKGROUND: Even though there is no consensus, many authors believe that in the
      cases of large hiatal defects, structurally altered crura and/or absence of
      peritoneal lining, a crural reinforcement should be performed. Reinforcement
      could be performed with different techniques and different type of mesh, either
      synthetic or biologic. The disadvantages of mesh repair include the possibility
      of serious complications and increased costs especially in the usage of composite
      or biologic mesh. METHODS: The study includes 10 cases of reinforced primary
      suture line of the pillars with autologous fascia lata, in elective laparoscopic
      repair of the giant PEH with a large hiatal defect and friable crura. After
      intraopreative confirmation of the large hiatal defect (hiatal surface area of
      more than 8 cm2) and friable crura, an autologous fascia lata graft was harvested
      in the usual manner and placed in on-lay fashion to reinforce the pillar suture
      line. We analyzed surgical technique, complications, and initial follow-up of the
      patients. RESULTS: Average hiatal surface area (HSA) in our series was 10.6 cm2
      (range 8.1 to 14.4 cm2). The average duration of operation was 203.9 min/3.4
      hours (range 160-250 min). Except for a mild hematoma in the harvesting region
      that resolved spontaneously, there were no procedure related complications and 30
      days mortality rate was zero. The average postoperative length of stay was 6.5
      days (5-8 days). Out of 10 patients, 5 completed the annual follow-up visit,
      while 8 completed a 6- month follow-up visit. So far there is no hernia
      recurrence and/or problems with swallowing function. However, one patient has
      felt a mild discomfort in the harvested region that does not influence normal
      daily activities. CONCLUSIONS: Autologous fascia lata graft hiatal reinforcement
      represents a technically feasible, easy, and available option for the on-lay
      reinforcement of large hiatal defects with friable crura in the laparoscopic
      repair of giant PEHs.

PMID- 25849294
TI  - Unraveling 14-3-3 proteins in C4 panicoids with emphasis on model plant Setaria
      italica reveals phosphorylation-dependent subcellular localization of RS splicing
      factor.
AB  - 14-3-3 proteins are a large multigenic family of regulatory proteins ubiquitously
      found in eukaryotes. In plants, 14-3-3 proteins are reported to play significant
      role in both development and response to stress stimuli. Therefore, considering
      their importance, genome-wide analyses have been performed in many plants
      including Arabidopsis, rice and soybean. But, till date, no comprehensive
      investigation has been conducted in any C4 panicoid crops. In view of this, the
      present study was performed to identify 8, 5 and 26 potential 14-3-3 gene family
      members in foxtail millet (Si14-3-3), sorghum (Sb14-3-3) and maize (Zm14-3-3),
      respectively. In silico characterization revealed large variations in their gene
      structures; segmental and tandem duplications have played a major role in
      expansion of these genes in foxtail millet and maize. Gene ontology annotation
      showed the participation of 14-3-3 proteins in diverse biological processes and
      molecular functions, and in silico expression profiling indicated their higher
      expression in all the investigated tissues. Comparative mapping was performed to
      derive the orthologous relationships between 14-3-3 genes of foxtail millet and
      other Poaceae members, which showed a higher, as well as similar percentage of
      orthology among these crops. Expression profiling of Si14-3-3 genes during
      different time-points of abiotic stress and hormonal treatments showed a
      differential expression pattern of these genes, and sub-cellular localization
      studies revealed the site of action of Si14-3-3 proteins within the cells.
      Further downstream characterization indicated the interaction of Si14-3-3 with a
      nucleocytoplasmic shuttling phosphoprotein (SiRSZ21A) in a phosphorylation
      dependent manner, and this demonstrates that Si14-3-3 might regulate the splicing
      events by binding with phosphorylated SiRSZ21A. Taken together, the present study
      is a comprehensive analysis of 14-3-3 gene family members in foxtail millet,
      sorghum and maize, which provides interesting information on their gene
      structure, protein domains, phylogenetic and evolutionary relationships, and
      expression patterns during abiotic stresses and hormonal treatments, which could
      be useful in choosing candidate members for further functional characterization.
      In addition, demonstration of interaction between Si14-3-3 and SiRSZ21A provides
      novel clues on the involvement of 14-3-3 proteins in the splicing events. 

PMID- 25849295
TI  - Modelling discrete choice variables in assessment of teaching staff work
      satisfaction.
AB  - Levels of self-reported job satisfaction and motivation were measured by survey
      in a sample of 286 teachers. Using the discrete choice framework, the paper tries
      to assess the relevance of the considered indicators (demographic, social,
      motivational) in overall teaching work satisfaction. The findings provide
      evidence that job satisfaction is correlated significantly with level of
      university degree held by the teacher, type of secondary school where the teacher
      is enrolled, revenues, and salary-tasks adequacy. This is important for the
      Romanian economy, since the education system is expected to provide future human
      resources with enhanced skills and abilities. 

PMID- 25849297
TI  - Predicting malignant and tuberculous pleural effusions through demographics and
      pleural fluid analysis of patients.
AB  - INTRODUCTION: The differential diagnosis of malignant and tuberculous pleural
      effusion is frequently difficult. OBJECTIVES: The aim of our study is to
      determine the discrimination value of demographic parameters and different
      biological markers in pleural fluid. METHODS: In pleural fluid obtained from 106
      patients with tuberculous, 250 with malignant and 218 with miscellaneous pleural
      effusion, clinical and analytical parameters were analysed, applying polytomous
      regression analysis and the receiver operating characteristic (ROC) curves.
      RESULTS: The three groups could be differentiated using the measured markers.
      Age, tumour necrosing factor-alpha, lactate dehydrogenase (LDH), adenosine
      deaminase (ADA), C-reactive protein (CRP) and carcinoembryonic antigen (CEA) were
      significant predictors for discriminating tuberculous from malignant pleural
      effusions; nucleated cells, lymphocytes, cholesterol, LDH, ADA, CRP, CEA and
      CA15.3 distinguish between malignant and miscellaneous pleural effusions. The ROC
      areas (95% confidence interval) were, 0.973 (0.953, 0.992) for tuberculous, 0.922
      (0.900, 0.943) for miscellaneous, and 0.927 (0.907, 0.948) for malignant pleural
      effusion. The polytomous model correctly classified a significantly high
      proportion of patients with tuberculosis (85.8%) and cancer (81.6%). The
      incorrect classification rate was 17.8%, which increased to 19.5% in the
      correction using bootstrap. CONCLUSIONS: The results obtained to estimate the
      probability of tuberculous and malignant pleural effusion confirm that this model
      achieves a high diagnostic accuracy. This model should be applied to determine
      which patients with a pleural effusion of unknown origin would not benefit from
      further invasive procedures.

PMID- 25849296
TI  - Fusarium oxysporum triggers tissue-specific transcriptional reprogramming in
      Arabidopsis thaliana.
AB  - Some of the most devastating agricultural diseases are caused by root-infecting
      pathogens, yet the majority of studies on these interactions to date have focused
      on the host responses of aerial tissues rather than those belowground. Fusarium
      oxysporum is a root-infecting pathogen that causes wilt disease on several plant
      species including Arabidopsis thaliana. To investigate and compare
      transcriptional changes triggered by F. oxysporum in different Arabidopsis
      tissues, we infected soil-grown plants with F. oxysporum and subjected root and
      leaf tissue harvested at early and late timepoints to RNA-seq analyses. At least
      half of the genes induced or repressed by F. oxysporum showed tissue-specific
      regulation. Regulators of auxin and ABA signalling, mannose binding lectins and
      peroxidases showed strong differential expression in root tissue. We demonstrate
      that ARF2 and PRX33, two genes regulated in the roots, promote susceptibility to
      F. oxysporum. In the leaves, defensins and genes associated with the response to
      auxin, cold and senescence were strongly regulated while jasmonate biosynthesis
      and signalling genes were induced throughout the plant. 

PMID- 25849298
TI  - Electromagnetic navigation-guided TBNA vs conventional TBNA in the diagnosis of
      mediastinal lymphadenopathy.
AB  - OBJECTIVES: Conventional transbronchial needle aspiration (C-TBNA) is a safe
      method for the diagnosis of hilar and mediastinal lymphadenopathy (MLN). However,
      diagnostic yield of this technique varies considerably. Electromagnetic
      navigation bronchoscopy (ENB) is a new technology to increase the diagnostic
      yield of flexible bronchoscopy for the peripheral lung lesions and MLN. The aim
      of this prospective study was to compare the diagnostic and sampling success of
      ENB-guided TBNA (ENB-TBNA) in comparison with C-TBNA while dealing with MLN.
      METHODS: Consecutive patients with MLN were randomized into two groups - C-TBNA
      and ENB-TBNA - using a computer-based number shuffling system to avoid
      recruitment bias. Procedures were performed in usual fashion, published
      previously. RESULTS: Ninety-four cases (M/F: 45/49) with a total of 145 stations
      of MLN were enrolled in the study. In 44 patients, 81 stations were sampled by
      ENB-TBNA, and in 50 patients 64 stations by C-TBNA. The mean size of MLN in study
      subjects was 17.56 +/- 6.25 mm. The sampling success was significantly higher in
      ENB-TBNA group (82.7%) compared with C-TBNA group (51.6%) (P < 0.005). Defined by
      histopathological result, the diagnostic yield in ENB-TBNA was 72.8%, and 42.2%
      with C-TBNA (P < 0.005). For subcarinal localization, sampling or diagnostic
      success was higher in ENB-TBNA than that of C-TBNA (P < 0.05). Based on the size
      of the MLN <=15 mm or >15 mm, the sampling success of ENB-TBNA was also
      significantly higher than C-TBNA in both subgroups (P < 0.005 and P < 0.005,
      respectively). No serious complication was observed. CONCLUSION: In this study
      comparing ENB-TBNA and C-TBNA, the sampling and diagnostic success of ENB-TBNA
      was found to be superior while dealing with MLN, in all categories studied.

PMID- 25849299
TI  - The clinical utility of Memorial Symptom Assessment-Short Form and Condensed
      Memorial Symptom Assessment Scale in Turkish lung cancer patients.
AB  - INTRODUCTION: Symptom assessment is essential in the palliative care of patients
      with cancer. We studied the Memorial Assessment Scale Test-Short Form (MSAS-SF)
      and Condensed Memorial Assessment Test (CMSAS) in Turkish lung cancer patients.
      MATERIAL AND METHOD: Fifty-one patients with lung cancer (47 non-small, 4 small
      cell) were staged according to the International Association for the Study of
      Lung Cancer 2007 and filled the MSAS-SF. Karnofsky performance status, TNM
      staging, MSAS-SF and CMSAS scores were recorded. The study was approved by the
      local research ethics committee. RESULTS: The mean age of 51 patients was 61.7 +/
      9. Fifty-one percent were staged as M1 while 49% were staged as M0. The mean
      values for global distress index, PHYS (physical symptom distress), PSYCH
      (psychological symptom score) and MSAS-SUM were 1.15 +/- 0.8, 0.9 +/- 0.8, 1.13
      +/- 1.03 and 0.82 +/- 0.47 in order. The mean values for CPHYS (physical symptom
      distress for Condensed MSAS), CPSYCH (psychological symptom score for CMSAS) and
      CSUM (sum scores) were 1.2 +/- 0.75, 1.22 +/- 1.1 and 1.16 +/- 0.69 in order.
      Cronbach's alpha coefficients for MSAS-SF and CMSAS were 0.861 and 0.728 in
      order. Summary scores for both MSAS-SF and CMSAS-SF were significantly higher in
      patients with M1 disease than from M0 disease. In addition, PHYS and MSAS-SUM in
      MSAS-SF were significantly correlated with T and N stage. The area under curve
      for MSAS-SF and CMSAS were 0.793 and 0.70 in order. CONCLUSION: MSAS-SF and CMSAS
      demonstrated significantly higher scores in lung cancer patients with M1 disease
      than patients with M0 disease. Further studies are needed to evaluate the
      usefulness of MSAS-SF and CMSAS in lung cancer patients.

PMID- 25849300
TI  - Cell wall modification in tobacco by differential targeting of recombinant
      endoglucanase from Trichoderma reesei.
AB  - BACKGROUND: The development of transgenic plants as a production platform for
      biomass-degrading enzymes is a promising tool for an economically feasible
      allocation of enzymes processing lignocellulose. Previous research has already
      identified a major limitation of in planta production such as interference with
      the structure and integrity of the plant cell wall resulting in a negative
      influence on plant growth and development. RESULTS: Here, we describe the in
      planta expression of endoglucanase TrCel5A from the mesophilic fungus Trichoderma
      reesei with differential intracellular targeting and evaluate its impact on the
      tobacco cell wall composition. Targeting of the enzyme to the apoplast leads to
      distinct changes in cell polysaccharides such as glucose level in the matrix
      polysaccharides (MPS). These effects are combined with severe changes in plant
      development. Retention of TrCel5A in the endoplasmic reticulum (ER) could avoid
      visible effects on plant growth under the chosen conditions, but exhibits changes
      in the composition of the MPS. CONCLUSIONS: These results give new insights into
      the complex interaction of heterologous cellulase expression with cell wall
      development and it outlines novel promising strategies to engineer plant cell
      walls for improved biomass processing.

PMID- 25849301
TI  - The RGS2 (-391, C>G) genetic variation correlates to antihypertensive drug
      responses in Chinese patients with essential hypertension.
AB  - OBJECTIVE: Regulators of G-protein signaling protein 2 (RGS2) play an
      irreplaceable role in the control of normal blood pressure (BP). One RGS2 (-391,
      C>G) genetic variation markedly changes its mRNA expression levels. This study
      explored the relationship between this genetic variation and the responses to
      antihypertensive drugs in Chinese patients with essential hypertension. METHODS:
      Genetic variations of RGS2 were successfully identified in 367 specimens using
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)
      assays. All patients were treated with conventional doses of antihypertensives
      after a 2-week run-in period and followed-up according to our protocol. A general
      linear model multivariate analysis of variance (ANOVA) was used for the data
      analysis. RESULTS: A significant difference in the mean systolic BP change was
      observed between RGS2 (-391, C>G) CC/CG (n = 82) and GG (n = 38) genotype
      carriers (-13.6 vs. -19.9 mmHg, P = 0.043) who were treated with candesartan,
      irbesartan or imidapril at the end of 6 weeks. In addition, the patients' BP
      responses to alpha,beta-adrenergic receptor blockers exhibited an age-specific
      association with the RGS2 (-391, C>G) genetic variation at the end of 4 weeks.
      CONCLUSION: The RGS2 (-391, C>G) genetic polymorphism may serve as a biomarker to
      predict a patient's response to antihypertensive drug therapy, but future studies
      need to confirm this.

PMID- 25849302
TI  - Decomposition of N-chloroglycine in alkaline aqueous solution: kinetics and
      mechanism.
AB  - The decomposition kinetics and mechanism of N-chloroglycine (MCG) was studied
      under very alkaline conditions ([OH(-)] = 0.01-0.10 M). The absorbance change is
      consistent with two consecutive first-order processes in the 220-350 nm
      wavelength range. The first reaction is linearly dependent on [OH(-)] and
      interpreted by the formation of a carbanion from MCG in an equilibrium step (KOH)
      and a subsequent loss of chloride ion from this intermediate: kobs1 = KOH k1 =
      (6.4 +/- 0.1) * 10(-2) M(-1) s(-1), I = 1.0 M (NaClO4), and T = 25.0  degrees C.
      The second process is assigned to the first-order decomposition of N
      oxalylglycine, which is also formed as an intermediate in this system: kobs2 =
      (1.2 +/- 0.1) * 10(-3) s(-1). Systematic (1)H and (13)C NMR measurements were
      performed in order to identify and follow the concentration changes of the
      reactant, intermediate, and product. It is confirmed that the decomposition
      proceeds via the formation of glyoxylate ion and produces N-formylglycine as a
      final product. This compound is stable for an extended period of time but
      eventually hydrolyses into formate and glycinate ions. A detailed mechanism is
      postulated which resolves the controversies found in earlier literature results.

PMID- 25849303
TI  - Cdx2 polymorphism affects the activities of vitamin D receptor in human breast
      cancer cell lines and human breast carcinomas.
AB  - Vitamin D plays a role in cancer development and acts through the vitamin D
      receptor (VDR). It regulates the action of hormone responsive genes and is
      involved in cell cycle regulation, differentiation and apoptosis. VDR is a
      critical component of the vitamin D pathway and different common single
      nucleotide polymorphisms have been identified. Cdx2 VDR polymorphism can play an
      important role in breast cancer, modulating the activity of VDR. The objective of
      this study is to assess the relationship between the Cdx2 VDR polymorphism and
      the activities of VDR in human breast cancer cell lines and carcinomas breast
      patients. Cdx2 VDR polymorphism and antiproliferative effects of vitamin D
      treatment were investigated in a panel of estrogen receptor-positive (MCF7 and T
      47D) and estrogen receptor-negative (MDA-MB-231, SUM 159PT, SK-BR-3, BT549, MDA
      MB-468, HCC1143, BT20 and HCC1954) human breast cancer cell lines. Furthermore,
      the potential relationship among Cdx2 VDR polymorphism and a number of biomarkers
      used in clinical management of breast cancer was assessed in an ad hoc set of
      breast cancer cases. Vitamin D treatment efficacy was found to be strongly
      dependent on the Cdx2 VDR status in ER-negative breast cancer cell lines tested.
      In our series of breast cancer cases, the results indicated that patients with
      variant homozygote AA were associated with bio-pathological characteristics
      typical of more aggressive tumours, such as ER negative, HER2 positive and G3.
      Our results may suggest a potential effect of Cdx2 VDR polymorphism on the
      efficacy of vitamin D treatment in aggressive breast cancer cells (estrogen
      receptor negative). These results suggest that Cdx2 polymorphism may be a
      potential biomarker for vitamin D treatment in breast cancer, independently of
      the VDR receptor expression. 

PMID- 25849304
TI  - The ageing shift worker: a prospective cohort study on need for recovery,
      disability, and retirement intentions.
AB  - OBJECTIVES: This study investigates whether different shift work schedules,
      compared to day work, are associated with need for recovery (NFR), future
      disability, and retirement intentions for employees employed within different
      economic sectors over the course of their careers. Shift work exposure duration
      and the healthy worker effect are also examined. METHODS: Data from the
      prospective Maastricht Cohort Study was used. Subsamples of industry (N=1877, all
      men) and healthcare (N=818, 624 women and 194 men) workers were separately
      investigated. GEE and Cox regression analyses were performed to investigate NFR
      longitudinally. Future disability was investigated using Cox regression, and
      retirement intentions were investigated using logistic regression analysis.
      RESULTS: Three-shift industry workers were at risk of becoming a case of elevated
      NFR during follow-up, compared to industry day workers. Three- and five-shift
      industry workers were at risk for future disability. In healthcare, irregular
      shift work was a risk factor for disability among older shift workers. No
      significant results were found regarding retirement intentions. Findings were
      probably an underestimation as exposure duration to shift work and the healthy
      worker effect affected the results. CONCLUSIONS: Shift work was associated with
      higher levels of NFR and a higher risk of disability. However, shift work is a
      multifaceted concept as different types of shift work schedules are differently
      associated with these outcomes. Different shift work types exist and shift work
      schedules allow for optimization, indicating that measures to prevent adverse
      outcomes should be tailored for different types of shift work and over the course
      of the work career.

PMID- 25849305
TI  - Transition from near-field thermal radiation to phonon heat conduction at sub
      nanometre gaps.
AB  - When the separation of two surfaces approaches sub-nanometre scale, the boundary
      between the two most fundamental heat transfer modes, heat conduction by phonons
      and radiation by photons, is blurred. Here we develop an atomistic framework
      based on microscopic Maxwell's equations and lattice dynamics to describe the
      convergence of these heat transfer modes and the transition from one to the
      other. For gaps >1 nm, the predicted conductance values are in excellent
      agreement with the continuum theory of fluctuating electrodynamics. However, for
      sub-nanometre gaps we find the conductance is enhanced up to four times compared
      with the continuum approach, while avoiding its prediction of divergent
      conductance at contact. Furthermore, low-frequency acoustic phonons tunnel
      through the vacuum gap by coupling to evanescent electric fields, providing
      additional channels for energy transfer and leading to the observed enhancement.
      When the two surfaces are in or near contact, acoustic phonons become dominant
      heat carriers. 

PMID- 25849306
TI  - Cross-Linking the Surface of Cured Polydimethylsiloxane via Hyperthemal Hydrogen
      Projectile Bombardment.
AB  - Cross-linking of polydimethylsiloxane (PDMS) is increasingly important with
      recent focus on its top surface stiffness. In this paper, we demonstrate that
      hyperthermal hydrogen projectile bombardment, a surface sensitive cross-linking
      technology, is superior in enhancing the mechanical properties of a cured PDMS
      surface without significantly degrading its hydrophobicity. Both water contact
      angle measurements and time-of-flight secondary ion mass spectrometry are used to
      investigate the variations in surface chemistry and structure upon cross-linking.
      Using nanoindentation and atomic force microscopy, we confirm that the thickness
      of the cross-linked PDMS is controllable by the bombardment time, which opens
      opportunities for tuning cross-linking degree in compliance with arising
      requirements from the practice. 

PMID- 25849307
TI  - NMR Analysis of Tuning Cross-Strand Phe/Tyr/Trp-Trp Interactions in Designed beta
      Hairpin Peptides: Terminal Switch from L to D Amino Acid as a Strategy for beta
      Hairpin Capping.
AB  - Interaction among the side chains of aromatic amino acids is a well-known
      mechanism of protein and peptide structure stabilization, particularly in beta
      sheets. Using short beta-hairpin models bearing the sequence Ac-Leu-Xxx-Val-DPro
      Gly-Leu-Trp-Val-NH2, we report the surprising observation of significant
      destabilization in aryl-tryptophan interactions, which results in poorly folded
      peptide populations accompanied by lowering of stability. We find that such
      destabilization arises from forced occupancy of the indole ring in the shielded
      Edge position, in T-shaped aryl geometries. We demonstrate that this
      destabilizing effect can be efficiently salvaged by replacing the N-terminal LLeu
      with DLeu, which causes an increase in the folded hairpin population, while
      retaining Trp in the Edge position. Our observation of unique cross strand NOEs
      and data from temperature-dependent NMR and CD measurements reveals the formation
      of a locally stabilized aliphatic-aromatic network, leading to an overall
      increase in DeltaGF degrees  by ~ -0.6 to -1.2 kcal/mol. Our results suggest that
      a contextual evaluation of stabilization by tryptophan is necessary in beta
      hairpins. Furthermore, we report for the first time that the use of D isomers of
      aliphatic amino acids at the terminus is stabilizing, which can serve as a new
      strategy for increasing beta-hairpin stability.

PMID- 25849308
TI  - Type 2 Diabetes Patients' Needs and Preferences for Care Concerning Sexual
      Problems: A Cross-Sectional Survey and Qualitative Interviews.
AB  - Sexual dysfunction is highly prevalent among patients with type 2 diabetes;
      however, little is known regarding these patients' needs and preferences for care
      for sexual problems. A cross-sectional survey and 25 semistructured interviews
      were therefore conducted among 40- to 75-year-old type 2 diabetes patients to
      explore this. We learned from the survey and interviews that most participants
      were unaware of the association between type 2 diabetes and sexual problems.
      Although certain barriers for discussing sexual problems with a care provider
      were identified (e.g., feelings of embarrassment), patients still reported a need
      for discussing their problems, because sex was viewed as an important part of
      their relationship. Some patients had sought help, but were dissatisfied with the
      offered care. Patients experienced a lack of attention and information from
      diabetes care providers. Improving this, together with a care provider-initiated
      conversation, was suggested to lower the threshold for discussion. Moreover,
      patients preferred a care provider with whom they have a close relationship,
      whereas age, gender, and medical specialty were regarded to be less important. An
      important recommendation was to make care for sexual problems an integral part of
      routine diabetes care. Future research should look into these recommendations. 

PMID- 25849309
TI  - Downregulation of hPMC2 imparts chemotherapeutic sensitivity to alkylating agents
      in breast cancer cells.
AB  - Triple negative breast cancer cell lines have been reported to be resistant to
      the cyotoxic effects of temozolomide (TMZ). We have shown previously that a novel
      protein, human homolog of Xenopus gene which Prevents Mitotic Catastrophe (hPMC2)
      has a role in the repair of estrogen-induced abasic sites. Our present study
      provides evidence that downregulation of hPMC2 in MDA-MB-231 and MDA-MB-468
      breast cancer cells treated with temozolomide (TMZ) decreases cell survival. This
      increased sensitivity to TMZ is associated with an increase in number of
      apurinic/apyrimidinic (AP) sites in the DNA. We also show that treatment with
      another alkylating agent, BCNU, results in an increase in AP sites and decrease
      in cell survival. Quantification of western blot analyses and immunofluorescence
      experiments reveal that treatment of hPMC2 downregulated cells with TMZ results
      in an increase in gamma-H2AX levels, suggesting an increase in double strand DNA
      breaks. The enhancement of DNA double strand breaks in TMZ treated cells upon
      downregulation of hPCM2 is also revealed by the comet assay. Overall, we provide
      evidence that downregulation of hPMC2 in breast cancer cells increases
      cytotoxicity of alkylating agents, representing a novel mechanism of treatment
      for breast cancer. Our data thus has important clinical implications in the
      management of breast cancer and brings forth potentially new therapeutic
      strategies. 

PMID- 25849310
TI  - Food, stress, and circulating testosterone: Cue integration by the testes, not
      the brain, in male zebra finches (Taeniopygia guttata).
AB  - Food abundance is closely associated with reproductive readiness in vertebrates.
      Food scarcity can activate the hypothalamo-pituitary-adrenal axis, decrease sex
      steroid secretion, and dampen reproductive behavior. However, the mechanisms
      underlying these transient effects are unclear. Gonadotropin inhibitory hormone
      (GnIH), a neuropeptide present in the brain and gonads, is also influenced by
      glucocorticoids and fasting in some species. We investigated whether fasting
      stress activated the GnIH system in zebra finches (Taeniopygia guttata), with the
      potential for downstream effects on reproductive physiology and behavior. We
      fasted or fed males ad libitum for 10h. Fasting increased corticosterone and
      decreased testosterone in circulation. To assess whether the decrease in
      testosterone was mediated by changes in the hypothalamus and/or the gonads, we
      (1) quantified GnRH- and GnIH-positive neurons in the hypothalamus, (2) assessed
      hypothalamic gene expression for GnRH and GnIH, and (3) examined gene expression
      for proteins involved in testosterone synthesis in fasted and control birds. No
      measure of hypothalamic neuropeptides was related to treatment or circulating
      steroids. However, birds with higher corticosterone had higher testicular GnIH
      expression and lower testosterone. StAR and LHR expression were lower in the
      testes of fasted birds than controls. Thus, the decrease in testosterone was not
      likely mediated by hypothalamic GnIH, but rather by direct actions of fasting
      and/or corticosterone on the testes, indicating that the testes can integrate and
      respond to cues of stress directly. Such local inhibition of testosterone
      synthesis may allow for rapid and reversible changes in physiology and behavior
      when conditions are inappropriate for breeding. 

PMID- 25849311
TI  - 2-Methyl-4-chlorophenoxyacetic acid and bromoxynil herbicide death.
AB  - CASE REPORT: We report a fatal case of a 37 year old gentleman who ingested a
      MCPA/bromoxynil co-formulation herbicide. Although clinically well on initial
      examination, our patient declined dramatically over his 18 h admission with
      increasing CO2 production, hyperthermia and metabolic derangement to eventually
      die from cardiac asystole 20 h post ingestion. Two hours after ingestion the MCPA
      concentration was 83.9 MUg/mL and bromoxynil concentration was 137 MUg/mL.
      DISCUSSION: The patients' mechanism of death appeared to be uncoupling of
      oxidative phosphorylation, excess CO2 production and hyperthermia. There is
      limited knowledge on the acute toxicity of these herbicides, in particular
      bromoxynil, and this case highlights the relentless progression of severe
      toxicity in humans.

PMID- 25849312
TI  - beta-D-2'-C-Methyl-2,6-diaminopurine Ribonucleoside Phosphoramidates are Potent
      and Selective Inhibitors of Hepatitis C Virus (HCV) and Are Bioconverted
      Intracellularly to Bioactive 2,6-Diaminopurine and Guanosine 5'-Triphosphate
      Forms.
AB  - The conversion of selected beta-D-2,6-diaminopurine nucleosides (DAPNs) to their
      phosphoramidate prodrug (PD) substantially blocks the conversion to the G-analog
      allowing for the generation of two bioactive nucleoside triphosphates (NTPs) in
      human hepatocytes. A variety of 2'-C-methyl DAPN-PDs were prepared and evaluated
      for inhibition of HCV viral replication in Huh-7 cells, cytotoxicity in various
      cell lines, and cellular pharmacology in both Huh-7 and primary human liver
      cells. The DAPN-PDs were pan-genotypic, effective against various HCV resistant
      mutants, and resistant variants could not be selected. 2'-C-Me-DAPN-TP and 2'-C
      Me-GTP were chain terminators for genotype 1b HCV-pol, and single nucleotide
      incorporation assays revealed that 2'-C-Me-DAPN-TP was incorporated opposite U.
      No cytotoxicity was observed with our DAPN-PD when tested up to 50 MUM. A novel,
      DAPN-PD, 15c, has been selected for further evaluation because of its good
      virologic and toxicologic profile and its ability to deliver two active
      metabolites, potentially simplifying HCV treatment.

PMID- 25849313
TI  - Nox-2 up-regulation and platelet activation: Novel insights.
AB  - Platelet activation is a key step in the onset of cardiovascular complications in
      patients affected by systemic atherosclerosis. Among other mechanisms, oxidative
      stress seems to play a crucial role in platelet activation. Reactive Oxidant
      Species (ROS) including O2(-), OH(-) or H2O2 act as second messenger to activate
      platelets via (1) calcium mobilization, (2) nitric oxide inactivation and (3)
      through the interaction with arachidonic acid to give formation of isoprostanes.
      One important source of ROS is represented by platelet NADPH oxidase. Growing
      data from experimental and clinical studies provide evidence that Nox2, the
      catalytic core of the NADPH oxidase system, is implicated in platelet activation.
      Accordingly, an impaired platelet activation has been described in patients with
      genetically determined Nox2 deficiency. Moreover, platelets added with specific
      inhibitors of Nox2 revealed impaired platelet activation, along with ROS down
      production. Similar results were seen in animals treated with apocynin, a Nox
      inhibitor, showed reduced platelet adhesion and atherosclerotic plaque. A
      significant association between Nox2 and platelet activation has been detected in
      patients with atherosclerotic diseases. The observed up-regulation of Nox2 with
      subsequent isoprostanes over-production in patients with cardiovascular diseases
      suggests the need to explore the potential benefit of targeting Nox2 as part of a
      holist anti-atherothrombotic strategy in patients with systemic atherosclerosis. 

PMID- 25849314
TI  - Co-solvents as stabilizing agents during heterologous overexpression in
      Escherichia coli - application to chlamydial penicillin-binding protein 6.
AB  - Heterologous overexpression of foreign proteins in Escherichia coli often leads
      to insoluble aggregates of misfolded inactive proteins, so-called inclusion
      bodies. To solve this problem use of chaperones or in vitro refolding procedures
      are the means of choice. These methods are time consuming and cost intensive, due
      to additional purification steps to get rid of the chaperons or the process of
      refolding itself. We describe an easy to use lab-scale method to avoid formation
      of inclusion bodies. The method systematically combines use of co-solvents,
      usually applied for in vitro stabilization of biologicals in biopharmaceutical
      formulation, and periplasmic expression and can be completed in one week using
      standard equipment in any life science laboratory. Demonstrating the unique power
      of our method, we overproduced and purified for the first time an active
      chlamydial penicillin-binding protein, demonstrated its function as penicillin
      sensitive DD-carboxypeptidase and took a major leap towards understanding the
      "chlamydial anomaly." 

PMID- 25849315
TI  - Prevalence study and genetic typing of bovine viral diarrhea virus (BVDV) in four
      bovine species in China.
AB  - To determine the nationwide status of persistent BVDV infection in different
      bovine species in China and compare different test methods, a total of 1379 serum
      samples from clinical healthy dairy cattle, beef cattle, yaks (Bos grunniens),
      and water buffalo (Bubalus bubalis) were collected in eight provinces of China
      from 2010 to 2013. The samples were analyzed using commercial antibody (Ab) and
      antigen (Ag) detection kits, and RT-PCR based on the 5'-UTR and Npro gene
      sequencing. Results showed that the overall positive rates for BVDV Ab, Ag and RT
      PCR detection were 58.09% (801/1379), 1.39% (14/1010), and 22.64% (146/645),
      respectively, while the individual positive rates varied among regions, species,
      and farms. The average Ab-positive rates for dairy cattle, beef cattle, yaks, and
      water buffalo were 89.49% (298/333), 63.27% (248/392), 45.38% (236/520), and
      14.18% (19/134), respectively, while the Ag-positive rates were 0.00% (0/116),
      0.77% (3/392), 0.82% (3/368), and 5.97% (8/134), respectively, and the nucleic
      acid-positive rates detected by RT-PCR were 32.06% (42/131), 13.00% (26/200),
      28.89% (52/180), and 19.40% (26/134), respectively. In addition, the RT-PCR
      products were sequenced and 124 5'-UTR sequences were obtained. Phylogenetic
      analysis of the 5'-UTR sequences indicated that all of the 124 BVDV-positive
      samples were BVDV-1 and subtyped into either BVDV-1b (33.06%), BVDV-1m (49.19%),
      or a new cluster, designated as BVDV-1u (17.74%). Phylogenetic analysis based on
      Npro sequences confirmed this novel subtype. In conclusion, this study revealed
      the prevalence of BVDV-1 in bovine species in China and the dominant subtypes.
      The high proportion of bovines with detectable viral nucleic acids in the sera,
      even in the presence of high Ab levels, revealed a serious threat to bovine
      health. 

PMID- 25849316
TI  - The measurement of amylase in drain fluid for the detection of pancreatic fistula
      after gastric cancer surgery: an interim analysis.
AB  - BACKGROUND: Pancreatic fistula is still one of the most serious and potential
      complications after D2-D3 distal and total gastrectomy (4% to 6%). Despite their
      importance, pancreatic fistulas still have not been uniformly defined. Amylase
      concentration of the drainage fluid after surgery for gastric cancer can be
      considered as a predictive factor of the presence of pancreatic fistula. METHODS:
      From January 2009 to April 2013, 53 patients underwent surgery for gastric
      cancer. Amylase concentration in the drainage fluid was measured on the first
      postoperative day and if it was >=1,000 UI, it was measured again on the third
      postoperative day. Pancreatic fistula occurred in four cases (7.5%). Pancreatic
      fistulas were classified using the International Study Group on Pancreatic
      Fistula (ISGPF) criteria into different grades of severity. Two fistulas were
      Grade A, one was Grade B, and one was Grade C. RESULTS: Management of drainage
      tubes is still crucial after gastrectomy, not only for the likelihood of
      anastomotic leaks but also the eventual diagnosis and management of pancreatic
      fistula. High amylase drainage content and then the presence of the pancreatic
      fistula may be due to several causes: the operation itself when it includes
      splenectomy or pancreatic tail-splenectomy, the extended lymphadenectomy but even
      the 'gently and softly' pancreatic manipulation, according literature, may be a
      risk factor. CONCLUSIONS: The authors assessed amylase concentration in the
      drainage fluid collected from the left subphrenic cavity on POD1 and POD3 in 53
      patients who had undergone curative gastrectomy for cancer and concluded that
      amylase drainage content >3 times the serum amylase was a useful predictive risk
      factor for pancreatic fistula. Our work is an interim analysis and the aim of
      this study is to increase the accrual of the number of patients to have a
      significant number. For this reason, a protocol for a multicenter trial will be
      designed to verify whether the systematic measurement of amylase in drain fluid
      is better than abdominal ultrasound for the detection of pancreatic fistula after
      gastric cancer surgery.

PMID- 25849317
TI  - Responses of two scleractinian corals to cobalt pollution and ocean
      acidification.
AB  - The effects of ocean acidification alone or in combination with warming on coral
      metabolism have been extensively investigated, whereas none of these studies
      consider that most coral reefs near shore are already impacted by other natural
      anthropogenic inputs such as metal pollution. It is likely that projected ocean
      acidification levels will aggravate coral reef health. We first investigated how
      ocean acidification interacts with one near shore locally abundant metal on the
      physiology of two major reef-building corals: Stylophora pistillata and Acropora
      muricata. Two pH levels (pHT 8.02; pCO2 366 MUatm and pHT 7.75; pCO2 1140 MUatm)
      and two cobalt concentrations (natural, 0.03 MUg L-1 and polluted, 0.2 MUg L-1)
      were tested during five weeks in aquaria. We found that, for both species, cobalt
      input decreased significantly their growth rates by 28% while it stimulated their
      photosystem II, with higher values of rETRmax (relative Electron Transport Rate).
      Elevated pCO2 levels acted differently on the coral rETRmax values and did not
      affect their growth rates. No consistent interaction was found between pCO2
      levels and cobalt concentrations. We also measured in situ the effect of higher
      cobalt concentrations (1.06 +/- 0.16 MUg L-1) on A. muricata using benthic
      chamber experiments. At this elevated concentration, cobalt decreased
      simultaneously coral growth and photosynthetic rates, indicating that the toxic
      threshold for this pollutant has been reached for both host cells and
      zooxanthellae. Our results from both aquaria and in situ experiments, suggest
      that these coral species are not particularly sensitive to high pCO2 conditions
      but they are to ecologically relevant cobalt concentrations. Our study reveals
      that some reefs may be yet subjected to deleterious pollution levels, and even if
      no interaction between pCO2 levels and cobalt concentration has been found, it is
      likely that coral metabolism will be weakened if they are subjected to additional
      threats such as temperature increase, other heavy metals, and eutrophication. 

PMID- 25849318
TI  - Time and Space resolved Methods: general discussion.

PMID- 25849319
TI  - Native American ancestry leads to complexity in 5-HTTLPR polymorphism association
      studies.

PMID- 25849322
TI  - Copper(I)-catalyzed intramolecular hydroalkoxylation of unactivated alkenes.
AB  - A Cu(I)-Xantphos system catalyzed the intramolecular hydroalkoxylation of
      unactivated terminal alkenes, giving five- and six-membered ring ethers. This
      system is applicable to both primary and secondary alcohols. A reaction pathway
      involving the addition of the Cu-O bond across the C-C double bond is proposed. A
      chiral Cu(I) catalyst system based on the (R)-DTBM-SEGPHOS ligand promoted
      enantioselective reaction with moderate enantioselectivity. 

PMID- 25849320
TI  - FKBP51 inhibits GSK3beta and augments the effects of distinct psychotropic
      medications.
AB  - Psychotropic medications target glycogen synthase kinase 3beta (GSK3beta), but
      the functional integration with other factors relevant for drug efficacy is
      poorly understood. We discovered that the suggested psychiatric risk factor FK506
      binding protein 51 (FKBP51) increases phosphorylation of GSK3beta at serine 9
      (pGSK3beta(S9)). FKBP51 associates with GSK3beta mainly through its FK1 domain;
      furthermore, it also changes GSK3beta's heterocomplex assembly by associating
      with the phosphatase PP2A and the kinase cyclin-dependent kinase 5. FKBP51 acts
      through GSK3beta on the downstream targets Tau, beta-catenin and T-cell
      factor/lymphoid enhancing factor (TCF/LEF). Lithium and the antidepressant (AD)
      paroxetine (PAR) functionally synergize with FKBP51, as revealed by reporter gene
      and protein association analyses. Deletion of FKBP51 blunted the PAR- or lithium
      induced increase in pGSK3beta(S9) in cells and mice and attenuated the behavioral
      effects of lithium treatment. Clinical improvement in depressive patients was
      predicted by baseline GSK3beta pathway activity and by pGSK3beta(S9) reactivity
      to ex vivo treatment of peripheral blood mononuclear lymphocytes with lithium or
      PAR. In sum, FKBP51-directed GSK3beta activity contributes to the action of
      psychotropic medications. Components of the FKBP51-GSK3beta pathway may be useful
      as biomarkers predicting AD response and as targets for the development of novel
      ADs. 

PMID- 25849321
TI  - Genes with de novo mutations are shared by four neuropsychiatric disorders
      discovered from NPdenovo database.
AB  - Currently, many studies on neuropsychiatric disorders have utilized massive trio
      based whole-exome sequencing (WES) and whole-genome sequencing (WGS) to identify
      numerous de novo mutations (DNMs). Here, we retrieved 17,104 DNMs from 3555 trios
      across four neuropsychiatric disorders: autism spectrum disorder, epileptic
      encephalopathy, intellectual disability and schizophrenia, in addition to
      unaffected siblings (control), from 36 studies by WES/WGS. After eliminating non
      exonic variants, we focused on 3334 exonic DNMs for evaluation of their
      association with these diseases. Our results revealed a higher prevalence of DNMs
      in the probands of all four disorders compared with the one in the controls
      (P<1.3 * 10(-7)). The elevated DNM frequency is dominated by loss-of
      function/deleterious single-nucleotide variants and frameshift indels (that is,
      extreme mutations, P<4.5 * 10(-5)). With extensive annotation of these 'extreme'
      mutations, we prioritized 764 candidate genes in these four disorders. A combined
      analysis of Gene Ontology, microRNA targets and transcription factor targets
      revealed shared biological process and non-coding regulatory elements of
      candidate genes in the pathology of neuropsychiatric disorders. In addition,
      weighted gene co-expression network analysis of human laminar-specific
      neocortical expression data showed that candidate genes are convergent on eight
      shared modules with specific layer enrichment and biological process features.
      Furthermore, we identified that 53 candidate genes are associated with more than
      one disorder (P<0.000001), suggesting a possibly shared genetic etiology
      underlying these disorders. Particularly, DNMs of the SCN2A gene are frequently
      occurred across all four disorders. Finally, we constructed a freely available
      NPdenovo database, which provides a comprehensive catalog of the DNMs identified
      in neuropsychiatric disorders.

PMID- 25849324
TI  - DMF Dimethyl Acetal as Carbon Source for alpha-Methylation of Ketones: A
      Hydrogenation-Hydrogenolysis Strategy of Enaminones.
AB  - A novel heterogeneous catalytic hydrogenation-hydrogenolysis strategy has been
      developed for the alpha-methylation of ketones via enaminones using DMF dimethyl
      acetal as carbon source. This strategy provides a very convenient route to alpha
      methylated ketones using a variety of ketones without any base or oxidant. 

PMID- 25849323
TI  - 1H NMR-based metabolomics investigation of copper-laden rat: a model of Wilson's
      disease.
AB  - BACKGROUND AND PURPOSE: Wilson's disease (WD), also known as hepatoleticular
      degeneration (HLD), is a rare autosomal recessive genetic disorder of copper
      metabolism, which causes copper to accumulate in body tissues. In this study,
      rats fed with copper-laden diet are used to render the clinical manifestations of
      WD, and their copper toxicity-induced organ lesions are studied. To investigate
      metabolic behaviors of 'decoppering' process, penicillamine (PA) was used for
      treating copper-laden rats as this chelating agent could eliminate excess copper
      through the urine. To date, there has been limited metabolomics study on WD,
      while metabolic impacts of copper accumulation and PA administration have yet to
      be established. MATERIALS AND METHODS: A combination of 1HNMR spectroscopy and
      multivariate statistical analysis was applied to examine the metabolic profiles
      of the urine and blood serum samples collected from the copper-laden rat model of
      WD with PA treatment. RESULTS: Copper accumulation in the copper-laden rats is
      associated with increased lactate, creatinine, valine and leucine, as well as
      decreased levels of glucose and taurine in the blood serum. There were also
      significant changes in p-hydroxyphenylacetate (p-HPA), creatinine, alpha
      ketoglutarate (alpha-KG), dimethylamine, N-acetylglutamate (NAG), N
      acetylglycoprotein (NAC) in the urine of these rats. Notably, the changes in p
      HPA, glucose, lactate, taurine, valine, leucine, and NAG were found reversed
      following PA treatment. Nevertheless, there were no changes for dimethylamine,
      alpha-KG, and NAC as a result of the treatment. Compared with the controls, the
      concentrations of hippurate, formate, alanine, and lactate were changed when PA
      was applied and this is probably due to its side effect. A tool named SMPDB
      (Small Molecule Pathway Database) is introduced to identify the metabolic pathway
      influenced by the copper-laden diet. CONCLUSION: The study has shown the
      potential application of NMR-based metabolomic analysis in providing further
      insights into the molecular mechanism underlying disorder due to WD.

PMID- 25849325
TI  - Modeling net ecosystem carbon exchange of alpine grasslands with a satellite
      driven model.
AB  - Estimate of net ecosystem carbon exchange (NEE) between the atmosphere and
      terrestrial ecosystems, the balance of gross primary productivity (GPP) and
      ecosystem respiration (Reco) has significant importance for studying the regional
      and global carbon cycles. Using models driven by satellite data and climatic data
      is a promising approach to estimate NEE at regional scales. For this purpose, we
      proposed a semi-empirical model to estimate NEE in this study. In our model, the
      component GPP was estimated with a light response curve of a rectangular
      hyperbola. The component Reco was estimated with an exponential function of soil
      temperature. To test the feasibility of applying our model at regional scales,
      the temporal variations in the model parameters derived from NEE observations in
      an alpine grassland ecosystem on Tibetan Plateau were investigated. The results
      indicated that all the inverted parameters exhibit apparent seasonality, which is
      in accordance with air temperature and canopy phenology. In addition, all the
      parameters have significant correlations with the remote sensed vegetation
      indexes or environment temperature. With parameters estimated with these
      correlations, the model illustrated fair accuracy both in the validation years
      and at another alpine grassland ecosystem on Tibetan Plateau. Our results also
      indicated that the model prediction was less accurate in drought years, implying
      that soil moisture is an important factor affecting the model performance.
      Incorporating soil water content into the model would be a critical step for the
      improvement of the model. 

PMID- 25849326
TI  - Crop-ecology and nutritional variability influence growth and secondary
      metabolites of Stevia rebaudiana Bertoni.
AB  - BACKGROUND: Plant nutrition and climatic conditions play important roles on the
      growth and secondary metabolites of stevia (Stevia rebaudiana Bertoni); however,
      the nutritional dose is strongly governed by the soil properties and climatic
      conditions of the growing region. In northern India, the interactive effects of
      crop ecology and plant nutrition on yield and secondary metabolites of stevia are
      not yet properly understood. Thus, a field experiment comprising three levels of
      nitrogen, two levels of phosphorus and three levels of potassium was conducted at
      three locations to ascertain whether the spatial and nutritional variability
      would dominate the leaf yield and secondary metabolites profile of stevia.
      RESULTS: Principal component analysis (PCA) indicates that the applications of 90
      kg N, 40 kg P2O5 and 40 kg K2O ha-1 are the best nutritional conditions in terms
      of dry leaf yield for CSIR-IHBT (Council of Scientific and Industrial Research-
      Institute Himalayan Bioresource Technology) and RHRS (Regional Horticultural
      Research Station) conditions. The spatial variability also exerted considerable
      effect on the leaf yield and stevioside content in leaves. Among the three
      locations, CSIR-IHBT was found most suitable in case of dry leaf yield and
      secondary metabolites accumulation in leaves. CONCLUSIONS: The results suggest
      that dry leaf yield and accumulation of stevioside are controlled by the
      environmental factors and agronomic management; however, the accumulation of
      rebaudioside-A (Reb-A) is not much influenced by these two factors. Thus, leaf
      yield and secondary metabolite profiles of stevia can be improved through the
      selection of appropriate growing locations and proper nutrient management.

PMID- 25849328
TI  - The Quebec rural emergency department project: a cross-sectional study of a
      potential two-pronged strategy in the knowledge transfer process.
AB  - INTRODUCTION: Health services research generates useful knowledge. Promotion of
      implementation of this knowledge in medical practice is essential. Prior to
      initiation of a major study on rural emergency departments (EDs), we deployed two
      knowledge transfer strategies designed to generate interest and engagement from
      potential knowledge users. The objective of this paper was to review: 1) a
      combined project launch and media press release strategy, and 2) a pre-study
      survey designed to survey potential knowledge users' opinions on the proposed
      study variables. MATERIALS AND METHODS: We evaluated the impact of the project
      launch (presentation at two conferences hosted by key stakeholders) and media
      press release via a survey of participants/stakeholders and by calculating the
      number of media interview requests and reports generated. We used a pre-study
      survey to collect potential key stakeholder' opinions on the study variables.
      RESULTS: Twenty-one of Quebec's 26 rural EDs participated in the pre-study survey
      (81% participation rate). The press release about the study generated 51 press
      articles and 20 media request for interviews, and contributed to public awareness
      of a major rural research initiative. In the pre-study survey, thirteen
      participants (46%) mentioned prior knowledge of the research project. Results
      from the pre-study survey revealed that all of the potential study variables were
      considered to be relevant for inclusion in the research project. Respondents also
      proposed additional variables of interest, including factors promoting retention
      of human resources. CONCLUSIONS: The present study demonstrated the potential
      utility of a two-pronged knowledge transfer strategy, including a combined formal
      launch and press release, and a pre-study survey designed to ensure that the
      included variables were of interest to participants and stakeholders.

PMID- 25849329
TI  - In vitro and in vivo metabolism and inhibitory activities of vasicine, a potent
      acetylcholinesterase and butyrylcholinesterase inhibitor.
AB  - Vasicine (VAS), a potential natural cholinesterase inhibitor, exhibited promising
      anticholinesterase activity in preclinical models and has been in development for
      treatment of Alzheimer's disease. This study systematically investigated the in
      vitro and in vivo metabolism of VAS in rat using ultra performance liquid
      chromatography combined with electrospray ionization quadrupole time-of-flight
      mass spectrometry. A total of 72 metabolites were found based on a detailed
      analysis of their 1H- NMR and 13C NMR data. Six key metabolites were isolated
      from rat urine and elucidated as vasicinone, vasicinol, vasicinolone, 1,2,3,9
      tetrahydropyrrolo [2,1-b] quinazolin-3-yl hydrogen sulfate, 9-oxo-1,2,3,9
      tetrahydropyrrolo [2,1-b] quinazolin-3-yl hydrogen sulfate, and 1,2,3,9
      tetrahydropyrrolo [2,1-b] quinazolin-3-beta-D-glucuronide. The metabolic pathway
      of VAS in vivo and in vitro mainly involved monohydroxylation, dihydroxylation,
      trihydroxylation, oxidation, desaturation, sulfation, and glucuronidation. The
      main metabolic soft spots in the chemical structure of VAS were the 3-hydroxyl
      group and the C-9 site. All 72 metabolites were found in the urine sample, and
      15, 25, 45, 18, and 11 metabolites were identified from rat feces, plasma, bile,
      rat liver microsomes, and rat primary hepatocyte incubations, respectively.
      Results indicated that renal clearance was the major excretion pathway of VAS.
      The acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory
      activities of VAS and its main metabolites were also evaluated. The results
      indicated that although most metabolites maintained potential inhibitory activity
      against AChE and BChE, but weaker than that of VAS. VAS undergoes metabolic
      inactivation process in vivo in respect to cholinesterase inhibitory activity. 

PMID- 25849330
TI  - FMS-like tyrosine kinase 3 ligand treatment does not ameliorate experimental
      rapidly progressive glomerulonephritis.
AB  - Fms-like tyrosine kinase 3-ligand (FL) is a growth factor that may expand
      dendritic cell and regulatory T cell populations. We hypothesised that FL-induced
      regulatory T cells would protect mice from experimental rapidly progressive
      glomerulonephritis. To determine if FL was able to enhance regulatory T cell
      populations, C57BL/6 mice received 10 days of daily intraperitoneal injections of
      either FL or phosphate buffered saline. To induce accelerated autologous-phase
      anti-mouse glomerular basement membrane glomerulonephritis, mice were sensitized
      to sheep globulin 4 days prior to the induction of glomerulonephritis with sheep
      anti-mouse glomerular basement membrane globulin, and experiments ended 10 days
      later. FL was administered before, throughout and during the sensitization phase
      of this glomerulonephritis model. Renal disease and systemic immunity to the
      nephritogenic antigen were assessed. FL increased regulatory T cell and
      plasmacytoid dendritic cell proportions within spleen and lymph nodes. FL
      administration prior to glomerulonephritis did not protect mice from renal
      injury. When FL was given throughout the model, FL treated mice had reduced
      survival, with more interstitial neutrophils and glomerular CD11c+ cells than
      controls. Systemic immune responses showed increased IL-17A production from
      splenocytes, with more CD11c+ cells, but reduced plasmacytoid dendritic cell
      proportions in spleen and lymph nodes, despite increased regulatory T cell
      proportions. Under homeostatic conditions, FL expanded regulatory T cell and
      plasmacytoid dendritic cell populations, but FL enhanced systemic inflammatory
      responses and conventional dendritic cell populations when given during
      experimental glomerulonephritis, suggesting selective attempts to suppress
      pathogenic immunity by dendritic cell manipulation may be harmful. 

PMID- 25849327
TI  - Assessment of variation in immunosuppressive pathway genes reveals TGFBR2 to be
      associated with prognosis of estrogen receptor-negative breast cancer after
      chemotherapy.
AB  - INTRODUCTION: Tumor lymphocyte infiltration is associated with clinical response
      to chemotherapy in estrogen receptor (ER) negative breast cancer. To identify
      variants in immunosuppressive pathway genes associated with prognosis after
      adjuvant chemotherapy for ER-negative patients, we studied stage I-III invasive
      breast cancer patients of European ancestry, including 9,334 ER-positive (3,151
      treated with chemotherapy) and 2,334 ER-negative patients (1,499 treated with
      chemotherapy). METHODS: We pooled data from sixteen studies from the Breast
      Cancer Association Consortium (BCAC), and employed two independent studies for
      replications. Overall 3,610 single nucleotide polymorphisms (SNPs) in 133 genes
      were genotyped as part of the Collaborative Oncological Gene-environment Study,
      in which phenotype and clinical data were collected and harmonized. Multivariable
      Cox proportional hazard regression was used to assess genetic associations with
      overall survival (OS) and breast cancer-specific survival (BCSS). Heterogeneity
      according to chemotherapy or ER status was evaluated with the log-likelihood
      ratio test. RESULTS: Three independent SNPs in TGFBR2 and IL12B were associated
      with OS (P <10-3) solely in ER-negative patients after chemotherapy (267 events).
      Poorer OS associated with TGFBR2 rs1367610 (G > C) (per allele hazard ratio (HR)
      1.54 (95% confidence interval (CI) 1.22 to 1.95), P = 3.08 * 10-4) was not found
      in ER-negative patients without chemotherapy or ER-positive patients with
      chemotherapy (P for interaction <10-3). Two SNPs in IL12B (r2 = 0.20) showed
      different associations with ER-negative disease after chemotherapy: rs2546892 (G
      > A) with poorer OS (HR 1.50 (95% CI 1.21 to 1.86), P = 1.81 * 10-4), and
      rs2853694 (A > C) with improved OS (HR 0.73 (95% CI 0.61 to 0.87), P = 3.67 * 10
      4). Similar associations were observed with BCSS. Association with TGFBR2
      rs1367610 but not IL12B variants replicated using BCAC Asian samples and the
      independent Prospective Study of Outcomes in Sporadic versus Hereditary Breast
      Cancer Study and yielded a combined HR of 1.57 ((95% CI 1.28 to 1.94), P = 2.05 *
      10-5) without study heterogeneity. CONCLUSIONS: TGFBR2 variants may have
      prognostic and predictive value in ER-negative breast cancer patients treated
      with adjuvant chemotherapy. Our findings provide further insights into the
      development of immunotherapeutic targets for ER-negative breast cancer.

PMID- 25849331
TI  - Fibroblast-myofibroblast transition is differentially regulated by bronchial
      epithelial cells from asthmatic children.
AB  - BACKGROUND: Airway remodeling is a proposed mechanism that underlies the
      persistent loss of lung function associated with childhood asthma. Previous
      studies have demonstrated that human lung fibroblasts (HLFs) co-cultured with
      primary human bronchial epithelial cells (BECs) from asthmatic children exhibit
      greater expression of extracellular matrix (ECM) components compared to co
      culture with BECs derived from healthy children. Myofibroblasts represent a
      population of differentiated fibroblasts that have greater synthetic activity. We
      hypothesized co-culture with asthmatic BECs would lead to greater fibroblast to
      myofibroblast transition (FMT) compared to co-culture with healthy BECs. METHODS:
      BECs were obtained from well-characterized asthmatic and healthy children and
      were proliferated and differentiated at an air-liquid interface (ALI). BEC-ALI
      cultures were co-cultured with HLFs for 96 hours. RT-PCR was performed in HLFs
      for alpha smooth muscle actin (alpha-SMA) and flow cytometry was used to assay
      for alpha-SMA antibody labeling of HLFs. RT-PCR was also preformed for the
      expression of tropomyosin-I as an additional marker of myofibroblast phenotype.
      In separate experiments, we investigated the role of TGFbeta2 in BEC-HLF co
      cultures using monoclonal antibody inhibition. RESULTS: Expression of alpha-SMA
      by HLFs alone was greater than by HLFs co-cultured with healthy BECs, but not
      different than alpha-SMA expression by HLFs co-cultured with asthmatic BECs. Flow
      cytometry also revealed significantly less alpha-SMA expression by healthy co-co
      cultures compared to asthmatic co-cultures or HLF alone. Monoclonal antibody
      inhibition of TGFbeta2 led to similar expression of alpha-SMA between healthy and
      asthmatic BEC-HLF co-cultures. Expression of topomyosin-I was also significantly
      increased in HLF co-cultured with asthmatic BECs compared to healthy BEC-HLF co
      cultures or HLF cultured alone. CONCLUSION: These findings suggest dysregulation
      of FMT in HLF co-cultured with asthmatic as compared to healthy BECs. Our results
      suggest TGFbeta2 may be involved in the differential regulation of FMT by
      asthmatic BECs. These findings further illustrate the importance of BEC-HLF cross
      talk in asthmatic airway remodeling.

PMID- 25849332
TI  - Use of the Blom Tracheotomy Tube with Suction Inner Cannula to Decontaminate
      Microorganisms from the Subglottic Space. A Proof of Concept.
AB  - RATIONALE: Preventing pulmonary complications during mechanical ventilation via
      tracheotomy is a high priority. OBJECTIVES: To investigate if the Blom
      tracheotomy tube with suction-above-the-cuff inner cannula reduced the quantity
      of normal flora and pathogens in supra- versus subglottic spaces. METHODS: We
      enrolled 20 consecutive medical ICU adults requiring tracheostomy for mechanical
      ventilation in this proof-of-concept, prospective, single-center study. All
      participants received a Blom tracheotomy tube with suction-above-the-cuff inner
      cannula to decontaminate microorganisms from the supra- and subglottic spaces.
      Supra- and subglottic sputum samples were obtained for microbiologic analysis
      while an endotracheal tube was in place before tracheotomy and once per week for
      up to 4 weeks of mechanical ventilation after tracheotomy. MEASUREMENTS AND MAIN
      RESULTS: Demographics, duration of endotracheal tube intubation, and duration of
      mechanical ventilation post-tracheotomy were recorded. There was a significant
      reduction for supraglottic (2.86 +/- 1.11 [mean +/- SD]) versus subglottic
      suction samples (2.48 +/- 1.07) (paired t test, P = 0.048; Wilcoxon test, P =
      0.045) when all data pairs for normal flora and pathogens were combined across
      times. There was a significant reduction of normal flora pooled across times in
      19 data pairs for supraglottic (3.00 +/- 1.05) versus subglottic suction samples
      (2.00 +/- 0.94) (paired t test, P = 0.0004; Wilcoxon test, P = 0.0007). There was
      no significant reduction of pathogens pooled across times in 25 data pairs for
      supraglottic (2.76 +/- 1.16) versus subglottic suction samples (2.84 +/- 1.03)
      (paired t test, P = 0.75; Wilcoxon test, P = 0.83). CONCLUSIONS: Proof-of-concept
      was confirmed. The Blom tracheotomy tube with disposable suction-above-the-cuff
      inner cannula decontaminated microorganisms from the subglottic space when normal
      flora and pathogens were combined. Future research should investigate if
      decreased quantity of normal flora and pathogens in the subglottic space reduces
      the incidence of ventilator-associated pulmonary complications in critically ill
      patients requiring ongoing mechanical ventilation via tracheotomy.

PMID- 25849333
TI  - An exploratory study on 99mTc-RGD-BBN peptide scintimammography in the assessment
      of breast malignant lesions compared to 99mTc-3P4-RGD2.
AB  - PURPOSE: This study aimed to explore the diagnostic performance of single photon
      emission computed tomography / computerized tomography (SPECT/CT) using a new
      radiotracer 99mTc-RGD-BBN for breast malignant tumor compared with 99mTc-3P4
      RGD2. METHODS: 6 female patients with breast malignant tumors diagnosed by fine
      needle aspiration cytology biopsy (FNAB) who were scheduled to undergo surgery
      were included in the study. 99mTc-3P4-RGD2 and 99mTc-RGD-BBN were performed with
      single photon emission computed tomography (SPECT) at 1 hour after intravenous
      injection of 299 +/- 30 MBq and 293 +/- 32 MBq of radiotracers respectively at
      separate day. The results were evaluated by the Tumor to non-Tumor ratios (T/NT).
      99mTc-RGD-BBN and 99mTc-3P4-RGD2 SPECT/CT images were interpreted independently
      by 3 experienced nuclear medicine physicians using a 3-point scale system. All of
      the samples were analyzed immunohistochemically to evaluate the integrin
      alphavbeta3 and gastrin-releasing peptide receptor (GRPR) expression. The safety,
      biodistribution and radiation dosimetry of 99mTc-RGD-BBN were also evaluated in
      the healthy volunteers. RESULTS: No serious adverse events were reported in any
      of the patients during the study. The effective radiation dose entirely conformed
      to the relevant standards. A total of 6 palpable malignant lesions were detected
      using 99mTc-RGD-BBN SPECT/CT with clear uptake. All malignant lesions were also
      detected using 99mTc-3P4-RGD2 SPECT/CT. The results showed that five malignant
      lesions were with clear uptake and the other one with barely an uptake. 4
      malignant cases were found with both alphavbeta3 and GRPR expression, 1 case with
      only GRPR positive expression (integrin alphavbeta3 negative) and 1 case with
      only integrin alphavbeta3 positive expression (GRPR negative). CONCLUSION: 99mTc
      RGD-BBN is a safe agent for detecting breast cancer. 99mTc-RGD-BBN may have the
      potential to make up for the deficiency of 99mTc-3P4-RGD2 in the detection of
      breast cancer with only GRPR positive expression (integrin alphavbeta3 negative).
      The preliminary application of 99mTc-RGD-BBN has demonstrated its powerful
      potential in breast cancer diagnosis and therapy.

PMID- 25849334
TI  - Genetic heterogeneity of the beta-globin gene in various geographic populations
      of Yunnan in southwestern China.
AB  - OBJECTIVES: The aim of this study was to investigate the geographic distribution
      of beta-globin gene mutations in different ethnic groups in Yunnan province.
      METHODS: From 2004 to 2014, 1,441 subjects with hemoglobin disorders, identified
      by PCR-reverse dot blot and DNA sequencing, were studied according to ethnicity
      and geographic origin. Haplotypes were examined among 41 unrelated thalassemia
      chromosomes. RESULTS: Eighteen beta-thalassemia mutations and seven hemoglobin
      variants were identified for 1,616 alleles in 22 different ethnic groups from all
      16 prefecture-level divisions of Yunnan. The prevalence of beta-thalassemia was
      heterogeneous and regionally specific. CD 41-42 (-TCTT) was the most prevalent
      mutation in the populations of northeastern Yunnan. CD 17 (A>T) was the most
      common mutation in the populations of southeastern Yunnan, especially for the
      Zhuang minority, whereas Hb E (CD 26, G>A) was the most prevalent mutation in
      populations of southwestern Yunnan, especially for the Dai minority. Among the
      seven types of haplotypes identified, CD 17 (A>T) was mainly linked to haplotype
      VII (+ - - - - - +) and IVS-II-654 (C>T) was only linked to haplotype I (+ - - - 
      + +). CONCLUSION: Our data underline the heterogeneity of beta-globin gene
      mutations in Yunnan. This distribution of beta-globin mutations in the geographic
      regions and ethnic populations provided a detailed ethnic basis and evolutionary
      view of humans in southern China, which will be beneficial for genetic counseling
      and prevention strategies.

PMID- 25849335
TI  - Tissue factor-expressing tumor cells can bind to immobilized recombinant tissue
      factor pathway inhibitor under static and shear conditions in vitro.
AB  - Mammary tumors and malignant breast cancer cell lines over-express the
      coagulation factor, tissue factor (TF). High expression of TF is associated with
      a poor prognosis in breast cancer. Tissue factor pathway inhibitor (TFPI), the
      endogenous inhibitor of TF, is constitutively expressed on the endothelium. We
      hypothesized that TF-expressing tumor cells can bind to immobilized recombinant
      TFPI, leading to arrest of the tumor cells under shear in vitro. We evaluated the
      adhesion of breast cancer cells to immobilized TFPI under static and shear
      conditions (0.35 - 1.3 dyn/cm2). We found that high-TF-expressing breast cancer
      cells, MDA-MB-231 (with a TF density of 460,000/cell), but not low TF-expressing
      MCF-7 (with a TF density of 1,400/cell), adhered to recombinant TFPI, under
      static and shear conditions. Adhesion of MDA-MB-231 cells to TFPI required
      activated factor VII (FVIIa), but not FX, and was inhibited by a factor VIIa
      blocking anti-TF antibody. Under shear, adhesion to TFPI was dependent on the
      TFPI-coating concentration, FVIIa concentration and shear stress, with no
      observed adhesion at shear stresses greater than 1.0 dyn/cm2. This is the first
      study showing that TF-expressing tumor cells can be captured by immobilized TFPI,
      a ligand constitutively expressed on the endothelium, under low shear in vitro.
      Based on our results, we hypothesize that TFPI could be a novel ligand mediating
      the arrest of TF-expressing tumor cells in high TFPI-expressing vessels under
      conditions of low shear during metastasis. 

PMID- 25849337
TI  - Controlled motion of Janus particles in periodically phase-separating binary
      fluids.
AB  - We numerically investigate the propelled motions of a Janus particle in a
      periodically phase-separating binary fluid mixture. In this study, the surface of
      the particle tail prefers one of the binary fluid components and the particle
      head is neutral in the wettability. During the demixing period, the more wettable
      phase is selectively adsorbed to the particle tail. Growths of the adsorbed
      domains induce the hydrodynamic flow in the vicinity of the particle tail, and
      this asymmetric pumping flow drives the particle toward the particle head. During
      the mixing period, the particle motion almost ceases because the mixing primarily
      occurs via diffusion and the resulting hydrodynamic flow is negligibly small.
      Repeating this cycle unboundedly moves the Janus particle toward the head. The
      dependencies of the composition and the repeat frequency on the particle motion
      are discussed. 

PMID- 25849336
TI  - RANK-ligand (RANKL) expression in young breast cancer patients and during
      pregnancy.
AB  - INTRODUCTION: RANKL is important in mammary gland development during pregnancy
      and mediates the initiation and progression of progesterone-induced breast
      cancer. No clinical data are available on the effect of pregnancy on RANK/RANKL
      expression in young breast cancer patients. METHODS: We used our previously
      published dataset of 65 pregnant and 130 matched young breast cancer patients
      with full clinical, pathological, and survival information. 85% of patients had
      available transcriptomic data as well. RANK/RANKL expression by
      immunohistochemistry using H-score on the primary tumor and adjacent normal
      tissue was performed. We examined the difference in expression of RANK/RANKL
      between pregnant and non-pregnant patients and their association with
      clinicopathological features and prognosis. We also evaluated genes and pathways
      associated with RANK/RANKL expression on primary tumors. RESULTS: RANKL but not
      RANK expression was more prevalent in the pregnant group, both on the tumor and
      adjacent normal tissue, independent of other clinicopathological factors (both P
      <0.001). 18.7% of pregnant and 5.3% of non-pregnant patients had tumors showing
      >=10% of cells with 3+ RANKL expression. RANKL expression was significantly
      higher in progesterone receptor-positive, and luminal A-like tumors, with
      negative correlation with Ki-67 (all P <0.001). On the contrary, RANK expression
      was higher in triple negative tumors (P <0.001). Using false discovery rate
      <0.05, 151 and 1,207 genes were significantly correlated with tumor-expressed
      RANKL and RANK expression by immunohistochemistry, respectively. High RANKL
      expression within primary tumor was associated with pathways related to mammary
      gland development, bone resorption, T-cell proliferation and regulation of
      chemotaxis, while RANK expression was associated with immune response and
      proliferation pathways. At a median follow-up of 65 months, neither RANK nor
      RANKL expression within tumor was associated with disease free survival in
      pregnant or non-pregnant group. CONCLUSIONS: Pregnancy increases RANKL expression
      both in normal breast and primary tumors. These results could guide further
      development of RANKL-targeted therapy.

PMID- 25849339
TI  - Supernumerary horseshoe kidneys.

PMID- 25849338
TI  - Liver-to-plasma vaniprevir (MK-7009) concentration ratios in HCV-infected
      patients.
AB  - BACKGROUND: Some drugs that are actively taken up into the liver exhibit greater
      than dose proportional increases in plasma exposure, although human liver-to
      plasma concentration ratios have rarely been evaluated. Understanding these
      relationships has implications for drug concentrations at the target site for
      certain classes of compounds, such as direct-acting antivirals, targeted towards
      HCV. METHODS: Treatment-experienced, chronic HCV non-cirrhotic patients (n=3)
      received vaniprevir (600 mg or 300 mg twice daily) on days 1-3 and (600 mg or 300
      mg single dose) on day 4. Core needle biopsy was performed at 6 or 12 h post-dose
      on day 4. Blood samples were collected pre-dose on days 1 and 4, and for 24 h
      post-dose on day 4. The primary study objective was the hepatic concentration of
      vaniprevir at 6 and 12 h post-dose. RESULTS: Vaniprevir plasma pharmacokinetic
      parameters increased in a greater than dose-proportional manner between the 300
      mg and 600 mg doses, with approximately fivefold increases in AUC0-12 and Cmax
      associated with a twofold increase in dose (AUC0-12, 10.6 MUM/h to 59.5 MUM/h;
      Cmax, 2.60 MUM to 13.5 MUM). In the 300 mg and 600 mg dose groups, mean liver
      concentrations of vaniprevir were 84.6 MUM and 169 MUM at 6 h post-dose, and 29.4
      MUM and 53.7 MUM at 12 h post-dose. Liver concentrations were higher than plasma
      with liver-to-plasma concentration ratios of approximately 20-280. CONCLUSIONS:
      These data confirm higher vaniprevir concentrations in human liver compared with
      plasma and demonstrate that measurement of human liver drug concentration using
      needle biopsy is feasible.

PMID- 25849340
TI  - Ictal depth EEG and MRI structural evidence for two different epileptogenic
      networks in mesial temporal lobe epilepsy.
AB  - Hypersynchronous (HYP) and low voltage fast (LVF) activity are two separate ictal
      depth EEG onsets patterns often recorded in presurgical patients with MTLE.
      Evidence suggests the mechanisms generating HYP and LVF onset seizures are
      distinct, including differential involvement of hippocampal and extra-hippocampal
      sites. Yet the extent of extra-hippocampal structural alterations, which could
      support these two common seizures, is not known. In the current study,
      preoperative MRI from 24 patients with HYP or LVF onset seizures were analyzed to
      determine changes in cortical thickness and relate structural changes to
      spatiotemporal properties of the ictal EEG. Overall, onset and initial
      ipsilateral spread of HYP onset seizures involved mesial temporal structures,
      whereas LVF onset seizures involved mesial and lateral temporal as well as
      orbitofrontal cortex. MRI analysis found reduced cortical thickness correlated
      with longer duration of epilepsy. However, in patients with HYP onsets, the most
      affected areas were on the medial surface of each hemisphere, including
      parahippocampal regions and cingulate gyrus, whereas in patients with LVF onsets,
      the lateral surface of the anterior temporal lobe and orbitofrontal cortex showed
      the greatest effect. Most patients with HYP onset seizures were seizure-free
      after resective surgery, while a higher proportion of patients with LVF onset
      seizures had only worthwhile improvement. Our findings confirm the view that
      recurrent seizures cause progressive changes in cortical thickness, and provide
      information concerning the structural basis of two different epileptogenic
      networks responsible for MTLE. One, identified by HYP ictal onsets, chiefly
      involves hippocampus and is associated with excellent outcome after standardized
      anteromedial temporal resection, while the other also involves lateral temporal
      and orbitofrontal cortex and a seizure-free surgical outcome occurs less after
      this procedure. These results suggest that a more extensive tailored resection
      may be required for patients with the second type of MTLE. 

PMID- 25849341
TI  - The anti-diabetic effects of GLP-1-gastrin dual agonist ZP3022 in ZDF rats.
AB  - AIMS/HYPOTHESIS: Combination treatment with exendin-4 and gastrin has proven
      beneficial in treatment of diabetes and preservation of beta cell mass in
      diabetic mice. Here, we examined the chronic effects of a GLP-1-gastrin dual
      agonist ZP3022 on glycemic control and beta cell dysfunction in overtly diabetic
      Zucker Diabetic Fatty (ZDF) rats. METHODS: ZDF rats aged 11 weeks were dosed
      s.c., b.i.d. for 8 weeks with vehicle, ZP3022, liraglutide, exendin-4, or gastrin
      17 with or without exendin-4. Glycemic control was assessed by measurements of
      HbA1c and blood glucose levels, as well as glucose tolerance during an oral
      glucose tolerance test (OGTT). Beta cell dynamics were examined by morphometric
      analyses of beta and alpha cell fractions. RESULTS: ZP3022 improved glycemic
      control as measured by terminal HbA1c levels (6.2+/-0.12 (high dose) vs. 7.9+/
      0.07% (vehicle), P<0.001), as did all treatments, except gastrin-17 monotherapy.
      In contrast, only ZP3022, exendin-4 and combination treatment with exendin-4 and
      gastrin-17 significantly improved glucose tolerance and increased insulin levels
      during an OGTT. Moreover, only ZP3022 significantly enhanced the beta cell
      fraction in ZDF rats, a difference of 41%, when compared to the vehicle group
      (0.31+/-0.03 vs. 0.22+/-0.02%, respectively, P<0.05). CONCLUSION: These data
      suggest that ZP3022 may have therapeutic potential in the prevention/delay of
      beta cell dysfunction in type 2 diabetes.

PMID- 25849342
TI  - Prediction of all-cause mortality with copeptin in cardio-cerebrovascular
      patients: A meta-analysis of prospective studies.
AB  - BACKGROUND: Measurement of the biomarker copeptin may help identify disease
      severity and risk of mortality for a various diseases. This study sought to
      determine the relationship between copeptin and all-cause mortality of patients
      with cardio-cerebrovascular disease. METHODS: Database of Medline and Web of
      Science were searched for studies with data involving the baseline copeptin
      levels and subsequent all-cause mortality outcomes. The pooled HRs of all-cause
      mortality were calculated and presented with 95%CIs. Subgroup analysis and
      sensitivity analysis were conducted to explore the possible sources of
      heterogeneity. RESULTS: Data from 14,395 participants were derived from 28
      prospective studies. Higher copeptin significantly increased the risk of all
      cause mortality (per unit copeptin: HR=1.020, 95%CI=1.004-1.036; log unit
      copeptin: HR=2.884, 95%CI=1.844-4.512; categorical copeptin: HR=3.371,
      95%CI=2.077-5.472). Subgroup analysis indicated that the risk of all-cause death
      was higher in cerebrovascular patients (per unit copeptin: HR=2.537, 95%CI=0.956
      6.731; log unit copeptin: HR=3.419, 95%CI=2.391-4.888) than cardiovascular
      patients (per unit copeptin: HR=1.011, 95%CI=1.002-1.020; log unit copeptin:
      HR=2.009, 95%CI=1.119-3.608). CONCLUSION: Copeptin is associated with all-cause
      mortality of patients with cardiovascular and cerebrovascular disease. Our study
      suggests that copeptin seems to be a promising novel biomarker for prediction of
      mortality in cardio-cerebrovascular patients, especially for cerebrovascular
      patients.

PMID- 25849343
TI  - Host-defense and trefoil factor family peptides in skin secretions of the Mawa
      clawed frog Xenopus boumbaensis (Pipidae).
AB  - Peptidomic analysis of norepinephrine-stimulated skin secretions from the
      octoploid Mawa clawed frog Xenopus boumbaensis Loumont, 1983 led to the
      identification and characterization of 15 host-defense peptides belonging to the
      magainin (two peptides), peptide glycine-leucine-amide (PGLa; three peptides),
      xenopsin precursor fragment (XPF; three peptides), caerulein precursor fragment
      (CPF; two peptides), and caerulein precursor fragment-related peptide (CPF-RP;
      five peptides) families. In addition, caerulein and three peptides with
      structural similarity to the trefoil factor family (TFF) peptides, xP2 and xP4
      from Xenopus laevis were also present in the secretions. Consistent with data
      from comparisons of the nucleotides sequence of mitochondrial and nuclear genes,
      the primary structures of the peptides suggest a close phylogenetic relationship
      between X. boumbaensis and the octoploid frogs Xenopus amieti and Xenopus andrei.
      As the three species occupy disjunct ranges within Cameroon, it is suggested that
      they diverged from a common ancestor by allopatric speciation. 

PMID- 25849344
TI  - Influences on influenza transmission within terminal based on hierarchical
      structure of personal contact network.
AB  - BACKGROUND: Since the outbreak of pandemics, influenza has caused extensive
      attention in the field of public health. It is actually hard to distinguish what
      is the most effective method to control the influenza transmission within airport
      terminal. The purpose of this study was to quantitatively evaluate the influences
      of passenger source, immunity difference and social relation structure on the
      influenza transmission in terminal. METHODS: A method combining hierarchical
      structure of personal contact network with agent-based SEIR model was proposed to
      analyze the characteristics of influenza diffusion within terminal. Based on the
      spatial distance between individuals, the hierarchical structure of personal
      contact network was defined to construct a complex relationship of passengers in
      the real world. Moreover, the agent-based SEIR model was improved by considering
      the individual level of influenza spread characteristics. To evaluate the method,
      this process was fused in simulation based on the constructed personal contact
      network. RESULTS: In the terminal we investigated, personal contact network was
      defined by following four layers: social relation structure, procedure partition,
      procedure area, and the whole terminal. With the growing of layer, the degree
      distribution curves move right. The value of degree distribution p(k) reached a
      peak at a specific value, and then back down. Besides, with the increase of layer
      alpha, the clustering coefficients presented a tendency to exponential decay.
      Based on the influenza transmission experiments, the main infected areas were
      concluded when considering different factors. Moreover, partition of passenger
      sources was found to impact a lot in departure, while social relation structure
      imposed a great influence in arrival. Besides, immunity difference exerted no
      obvious effect on the spread of influenza in the transmission process both in
      departure and arrival. CONCLUSIONS: The proposed method is efficient to reproduce
      the evolution process of influenza transmission, and exhibits various roles of
      each factor in different processes, also better reflects the effect of passenger
      topological character on influenza spread. It contributes to proposing effective
      influenza measures by airport relevant department and improving the efficiency
      and ability of epidemic prevention on the public health.

PMID- 25849345
TI  - Direct evaluation of molecular States of piroxicam/poloxamer nanosuspension by
      suspended-state NMR and Raman spectroscopies.
AB  - A nanosuspension of piroxicam (PXC) and poloxamer 407 (poloxamer) prepared by the
      wet milling method was directly evaluated at the molecular level from the
      viewpoint of both solution and solid phases. (13)C solution-state NMR
      measurements revealed a reduction in the concentration of dissolved poloxamer in
      the nanosuspension. Furthermore, the fraction of dissolved poly(ethylene oxide)
      (PEO) chain, which is the hydrophilic part of poloxamer, was higher than that of
      dissolved poly(propylene oxide) (PPO) chain, the hydrophobic part. (13)C
      suspended-state NMR and Raman spectroscopies detected both solid-state PXC and
      poloxamer involved in the nanoparticles. Interestingly, the coexistence of
      crystalline and amorphous PXC in the nanoparticle was demonstrated. The yellow
      color of the nanosuspension strongly supported the existence of amorphous PXC.
      Changes in the peak intensity depending on the contact time in the suspended
      state NMR spectrum revealed that the PEO chain of poloxamer in the nanoparticle
      had higher mobility compared with the PPO chain. The PEO chain should project
      into the water phase and form the outer layer of the nanoparticles, whereas the
      PPO chain should face the inner side of the nanoparticles. Amorphous PXC could be
      stabilized by intermolecular interaction with the PPO chain near the surface of
      the nanoparticles, whereas crystalline PXC could form the inner core. 

PMID- 25849347
TI  - The Scanning TMR Microscope for Biosensor Applications.
AB  - We present a novel tunnel magnetoresistance (TMR) scanning microscope set-up
      capable of quantitatively imaging the magnetic stray field patterns of micron
      sized elements in 3D. By incorporating an Anderson loop measurement circuit for
      impedance matching, we are able to detect magnetoresistance changes of as little
      as 0.006%/Oe. By 3D rastering a mounted TMR sensor over our magnetic barcodes, we
      are able to characterize the complex domain structures by displaying the real
      component, the amplitude and the phase of the sensor's impedance. The modular
      design, incorporating a TMR sensor with an optical microscope, renders this set
      up a versatile platform for studying and imaging immobilised magnetic carriers
      and barcodes currently employed in biosensor platforms, magnetotactic bacteria
      and other complex magnetic domain structures of micron-sized entities. The
      quantitative nature of the instrument and its ability to produce vector maps of
      magnetic stray fields has the potential to provide significant advantages over
      other commonly used scanning magnetometry techniques.

PMID- 25849346
TI  - Plasma membrane mechanical stress activates TRPC5 channels.
AB  - Mechanical forces exerted on cells impose stress on the plasma membrane. Cells
      sense this stress and elicit a mechanoelectric transduction cascade that
      initiates compensatory mechanisms. Mechanosensitive ion channels in the plasma
      membrane are responsible for transducing the mechanical signals to electrical
      signals. However, the mechanisms underlying channel activation in response to
      mechanical stress remain incompletely understood. Transient Receptor Potential
      (TRP) channels serve essential functions in several sensory modalities. These
      channels can also participate in mechanotransduction by either being autonomously
      sensitive to mechanical perturbation or by coupling to other mechanosensory
      components of the cell. Here, we investigated the response of a TRP family
      member, TRPC5, to mechanical stress. Hypoosmolarity triggers Ca2+ influx and
      cationic conductance through TRPC5. Importantly, for the first time we were able
      to record the stretch-activated TRPC5 current at single-channel level. The
      activation threshold for TRPC5 was found to be 240 mOsm for hypoosmotic stress
      and between -20 and -40 mmHg for pressure applied to membrane patch. In addition,
      we found that disruption of actin filaments suppresses TRPC5 response to
      hypoosmotic stress and patch pipette pressure, but does not prevent the
      activation of TRPC5 by stretch-independent mechanisms, indicating that actin
      cytoskeleton is an essential transduction component that confers
      mechanosensitivity to TRPC5. In summary, our findings establish that TRPC5 can be
      activated at the single-channel level when mechanical stress on the cell reaches
      a certain threshold. 

PMID- 25849348
TI  - The impact of the carer support needs assessment tool (CSNAT) in community
      palliative care using a stepped wedge cluster trial.
AB  - Family caregiving towards the end-of-life entails considerable emotional, social,
      financial and physical costs for caregivers. Evidence suggests that good support
      can improve caregiver psychological outcomes. The primary aim of this study was
      to investigate the impact of using the carer support needs assessment tool
      (CSNAT), as an intervention to identify and address support needs in end of life
      home care, on family caregiver outcomes. A stepped wedge design was used to trial
      the CSNAT intervention in three bases of Silver Chain Hospice Care in Western
      Australia, 2012-14. The intervention consisted of at least two visits from nurses
      (2-3 weeks apart) to identify, review and address caregivers' needs. The outcome
      measures for the intervention and control groups were caregiver strain and
      distress as measured by the Family Appraisal of Caregiving Questionnaire (FACQ
      PC), caregiver mental and physical health as measured by SF-12v2, and caregiver
      workload as measured by extent of caregiver assistance with activities of daily
      living, at baseline and follow up. Total recruitment was 620. There was 45%
      attrition for each group between baseline and follow-up mainly due to patient
      deaths resulting in 322 caregivers completing the study (233 in the intervention
      group and 89 in the control group). At follow-up, the intervention group showed
      significant reduction in caregiver strain relative to controls, p=0.018, d=0.348
      (95% CI 0.25 to 0.41). Priority support needs identified by caregivers included
      knowing what to expect in the future, having time for yourself in the day and
      dealing with your feelings and worries. Despite the challenges at the clinician,
      organisational and trial levels, the CSNAT intervention led to an improvement in
      caregiver strain. Effective implementation of an evidence-informed and caregiver
      led tool represents a necessary step towards helping palliative care providers
      better assess and address caregiver needs, ensuring adequate family caregiver
      support and reduction in caregiver strain. 

PMID- 25849349
TI  - Embodied choice: how action influences perceptual decision making.
AB  - Embodied Choice considers action performance as a proper part of the decision
      making process rather than merely as a means to report the decision. The central
      statement of embodied choice is the existence of bidirectional influences between
      action and decisions. This implies that for a decision expressed by an action,
      the action dynamics and its constraints (e.g. current trajectory and kinematics)
      influence the decision making process. Here we use a perceptual decision making
      task to compare three types of model: a serial decision-then-action model, a
      parallel decision-and-action model, and an embodied choice model where the action
      feeds back into the decision making. The embodied model incorporates two key
      mechanisms that together are lacking in the other models: action preparation and
      commitment. First, action preparation strategies alleviate delays in enacting a
      choice but also modify decision termination. Second, action dynamics change the
      prospects and create a commitment effect to the initially preferred choice. Our
      results show that these two mechanisms make embodied choice models better suited
      to combine decision and action appropriately to achieve suitably fast and
      accurate responses, as usually required in ecologically valid situations.
      Moreover, embodied choice models with these mechanisms give a better account of
      trajectory tracking experiments during decision making. In conclusion, the
      embodied choice framework offers a combined theory of decision and action that
      gives a clear case that embodied phenomena such as the dynamics of actions can
      have a causal influence on central cognition. 

PMID- 25849350
TI  - Restoration of motion-blurred image based on border deformation detection: a
      traffic sign restoration model.
AB  - Due to the rapid development of motor vehicle Driver Assistance Systems (DAS),
      the safety problems associated with automatic driving have become a hot issue in
      Intelligent Transportation. The traffic sign is one of the most important tools
      used to reinforce traffic rules. However, traffic sign image degradation based on
      computer vision is unavoidable during the vehicle movement process. In order to
      quickly and accurately recognize traffic signs in motion-blurred images in DAS, a
      new image restoration algorithm based on border deformation detection in the
      spatial domain is proposed in this paper. The border of a traffic sign is
      extracted using color information, and then the width of the border is measured
      in all directions. According to the width measured and the corresponding
      direction, both the motion direction and scale of the image can be confirmed, and
      this information can be used to restore the motion-blurred image. Finally, a gray
      mean grads (GMG) ratio is presented to evaluate the image restoration quality.
      Compared to the traditional restoration approach which is based on the blind
      deconvolution method and Lucy-Richardson method, our method can greatly restore
      motion blurred images and improve the correct recognition rate. Our experiments
      show that the proposed method is able to restore traffic sign information
      accurately and efficiently. 

PMID- 25849351
TI  - Dietary n-3 polyunsaturated fatty acid intakes modify the effect of genetic
      variation in fatty acid desaturase 1 on coronary artery disease.
AB  - BACKGROUND: Previous studies suggested that dietary fatty acids could affect
      blood lipids by interacting with genetic variations in fatty acid desaturase 1
      (FADS1). However, little is known about their direct effects on coronary artery
      disease (CAD). The aim of this study was to evaluate whether dietary n-3 long
      chain polyunsaturated fatty acids (LCPUFAs)-eicosapentaenoic acid (EPA) and
      docosahexaenoic acid (DHA) could modulate the effect of FADS1 rs174547
      polymorphism on CAD. METHODS: FADS1 single-nucleotide polymorphisms rs174547
      genotypes were measured in 440 CAD patients and 838 healthy controls. Dietary EPA
      and DHA intakes were assessed with a validated quantitative frequency food
      questionnaire. The association between FADS1 rs174547 and CAD was estimated using
      logistic regression under both dominant and additive genetic models. The
      interactions between rs174547 polymorphism and LCPUFAs were analyzed by using
      multiple logistic regression and the "genotype * n-3 LCPUFAs" interaction term
      was included into the model. RESULTS: We found that the minor T allele of FADS1
      rs174547 increased CAD risk (OR = 1.36, 95%CIs 1.03-1.80), and observed
      significant interaction between rs174547 and dietary EPA intakes on CAD (P
      interaction = 0.028). The T-allele was only associated with higher CAD risk among
      individuals with lower dietary EPA intakes, but not in those with higher EPA
      intakes. Similarly, significant interaction was also observed between rs174547
      and dietary DHA intakes on CAD (P-interaction = 0.020). CONCLUSIONS: Dietary n-3
      LCPUFA intakes could modulate the association between FADS1 rs174547 polymorphism
      and CAD. High dietary n-3 LCPUFA intakes could negate the unfavorable effect of
      genetic variation in FADS1 on CAD in middle-aged and elderly Chinese population.

PMID- 25849353
TI  - Correction: identification of modulators of the nuclear receptor peroxisome
      proliferator-activated receptor alpha (PPARalpha) in a mouse liver gene
      expression compendium.

PMID- 25849354
TI  - Gonadotropin-releasing hormone agonist overuse: urologists' response to
      reimbursement and characteristics associated with persistent overuse.
AB  - BACKGROUND: Medicare reimbursement cuts have been associated with declining
      gonadotropin-releasing hormone (GnRH) agonist overuse in localized prostate
      cancer. Medical school affiliation and foreign training have been associated with
      persistent overuse. However, physician-level prescribing changes and the practice
      type of persistent overusers have not been examined. We sought to describe
      physician-level changes in GnRH agonist overuse and test the association of time
      in practice and solo practice type with GnRH agonist overuse. METHODS: We matched
      American Medical Association physician data for 2138 urologists to Surveillance,
      Epidemiology and End Result-Medicare data for 12,943 men diagnosed with early
      stage and lower-grade adenocarcinoma of the prostate between 2000 and 2007. We
      conducted a population-based, retrospective study using multilevel modeling to
      control for patient and provider characteristics. RESULTS: Three distinct
      patterns of GnRH agonist overuse were observed. Urologists' time in practice was
      not associated with GnRH agonist overuse (odds ratio (OR) 0.89; 95% confidence
      interval (CI): 0.75-1.05). However, solo practice type (OR 1.65; 95% CI: 1.34
      2.02), medical school affiliation (OR 0.65; 95% CI: 0.55-0.77) and patient race
      were. Compared with non-Hispanic whites, non-Hispanic blacks (OR 1.76; 95% CI:
      1.37-2.27), Hispanics (OR 1.41; 95% CI: 1.12-1.79) and men of 'other' race (OR
      1.44; 95% CI: 1.04-1.99) had greater odds of receiving unnecessary GnRH agonists.
      CONCLUSIONS: GnRH agonist overuse remains high among some urologists who may be
      professionally isolated and difficult to reach. These urologists treat more
      vulnerable populations, which may contribute to health disparities in prostate
      cancer treatment quality. Nonetheless, these findings provide guidance to develop
      interventions to address overuse in prostate cancer.

PMID- 25849355
TI  - Endocytosis as a biological response in receptor pharmacology: evaluation by
      fluorescence microscopy.
AB  - The activation of G-protein coupled receptors by agonist compounds results in
      diverse biological responses in cells, such as the endocytosis process consisting
      in the translocation of receptors from the plasma membrane to the cytoplasm
      within internalizing vesicles or endosomes. In order to functionally evaluate
      endocytosis events resulted from pharmacological responses, we have developed an
      image analysis method -the Q-Endosomes algorithm- that specifically discriminates
      the fluorescent signal originated at endosomes from that one observed at the
      plasma membrane in images obtained from living cells by fluorescence microscopy.
      Mu opioid (MOP) receptor tagged at the carboxy-terminus with yellow fluorescent
      protein (YFP) and permanently expressed in HEK293 cells was used as experimental
      model to validate this methodology. Time-course experiments performed with
      several agonists resulted in different sigmoid curves depending on the drug used
      to initiate MOP receptor endocytosis. Thus, endocytosis resulting from the
      simultaneous activation of co-expressed MOP and serotonin 5-HT2C receptors by
      morphine plus serotonin was significantly different, in kinetics as well as in
      maximal response parameters, from the one caused by DAMGO, sufentanyl or
      methadone. Therefore, this analytical tool permits the pharmacological
      characterization of receptor endocytosis in living cells with functional and
      temporal resolution. 

PMID- 25849352
TI  - Geographic and temporal trends in the molecular epidemiology and genetic
      mechanisms of transmitted HIV-1 drug resistance: an individual-patient- and
      sequence-level meta-analysis.
AB  - BACKGROUND: Regional and subtype-specific mutational patterns of HIV-1
      transmitted drug resistance (TDR) are essential for informing first-line
      antiretroviral (ARV) therapy guidelines and designing diagnostic assays for use
      in regions where standard genotypic resistance testing is not affordable. We
      sought to understand the molecular epidemiology of TDR and to identify the HIV-1
      drug-resistance mutations responsible for TDR in different regions and virus
      subtypes. METHODS AND FINDINGS: We reviewed all GenBank submissions of HIV-1
      reverse transcriptase sequences with or without protease and identified 287
      studies published between March 1, 2000, and December 31, 2013, with more than 25
      recently or chronically infected ARV-naive individuals. These studies comprised
      50,870 individuals from 111 countries. Each set of study sequences was analyzed
      for phylogenetic clustering and the presence of 93 surveillance drug-resistance
      mutations (SDRMs). The median overall TDR prevalence in sub-Saharan Africa (SSA),
      south/southeast Asia (SSEA), upper-income Asian countries, Latin
      America/Caribbean, Europe, and North America was 2.8%, 2.9%, 5.6%, 7.6%, 9.4%,
      and 11.5%, respectively. In SSA, there was a yearly 1.09-fold (95% CI: 1.05-1.14)
      increase in odds of TDR since national ARV scale-up attributable to an increase
      in non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance. The odds of
      NNRTI-associated TDR also increased in Latin America/Caribbean (odds ratio [OR] =
      1.16; 95% CI: 1.06-1.25), North America (OR = 1.19; 95% CI: 1.12-1.26), Europe
      (OR = 1.07; 95% CI: 1.01-1.13), and upper-income Asian countries (OR = 1.33; 95%
      CI: 1.12-1.55). In SSEA, there was no significant change in the odds of TDR since
      national ARV scale-up (OR = 0.97; 95% CI: 0.92-1.02). An analysis limited to
      sequences with mixtures at less than 0.5% of their nucleotide positions-a proxy
      for recent infection-yielded trends comparable to those obtained using the
      complete dataset. Four NNRTI SDRMs-K101E, K103N, Y181C, and G190A-accounted for
      >80% of NNRTI-associated TDR in all regions and subtypes. Sixteen nucleoside
      reverse transcriptase inhibitor (NRTI) SDRMs accounted for >69% of NRTI
      associated TDR in all regions and subtypes. In SSA and SSEA, 89% of NNRTI SDRMs
      were associated with high-level resistance to nevirapine or efavirenz, whereas
      only 27% of NRTI SDRMs were associated with high-level resistance to zidovudine,
      lamivudine, tenofovir, or abacavir. Of 763 viruses with TDR in SSA and SSEA, 725
      (95%) were genetically dissimilar; 38 (5%) formed 19 sequence pairs. Inherent
      limitations of this study are that some cohorts may not represent the broader
      regional population and that studies were heterogeneous with respect to duration
      of infection prior to sampling. CONCLUSIONS: Most TDR strains in SSA and SSEA
      arose independently, suggesting that ARV regimens with a high genetic barrier to
      resistance combined with improved patient adherence may mitigate TDR increases by
      reducing the generation of new ARV-resistant strains. A small number of NNRTI
      resistance mutations were responsible for most cases of high-level resistance,
      suggesting that inexpensive point-mutation assays to detect these mutations may
      be useful for pre-therapy screening in regions with high levels of TDR. In the
      context of a public health approach to ARV therapy, a reliable point-of-care
      genotypic resistance test could identify which patients should receive standard
      first-line therapy and which should receive a protease-inhibitor-containing
      regimen.

PMID- 25849356
TI  - Rural, urban and migrant differences in non-communicable disease risk-factors in
      middle income countries: a cross-sectional study of WHO-SAGE data.
AB  - BACKGROUND: Understanding how urbanisation and rural-urban migration influence
      risk-factors for non-communicable disease (NCD) is crucial for developing
      effective preventative strategies globally. This study compares NCD risk-factor
      prevalence in urban, rural and migrant populations in China, Ghana, India,
      Mexico, Russia and South Africa. METHODS: Study participants were 39,436 adults
      within the WHO Study on global AGEing and adult health (SAGE), surveyed 2007
      2010. Risk ratios (RR) for each risk-factor were calculated using logistic
      regression in country-specific and all country pooled analyses, adjusted for age,
      sex and survey design. Fully adjusted models included income quintile, marital
      status and education. RESULTS: Regular alcohol consumption was lower in migrant
      and urban groups than in rural groups (pooled RR and 95%CI: 0.47 (0.31-0.68);
      0.58, (0.46-0.72), respectively). Occupational physical activity was lower (0.86
      (0.72-0.98); 0.76 (0.65-0.85)) while active travel and recreational physical
      activity were higher (pooled RRs for urban groups; 1.05 (1.00-1.09), 2.36 (1.95
      2.83), respectively; for migrant groups: 1.07 (1.0 -1.12), 1.71 (1.11-2.53),
      respectively). Overweight, raised waist circumference and diagnosed diabetes were
      higher in urban groups (1.19 (1.04-1.35), 1.24 (1.07-1.42), 1.69 (1.15-2.47),
      respectively). Exceptions to these trends exist: obesity indicators were higher
      in rural Russia; active travel was lower in urban groups in Ghana and India; and
      in South Africa, urban groups had the highest alcohol consumption. CONCLUSION:
      Migrants and urban dwellers had similar NCD risk-factor profiles. These were not
      consistently worse than those seen in rural dwellers. The variable impact of
      urbanisation on NCD risk must be considered in the design and evaluation of
      strategies to reduce the growing burden of NCDs globally.

PMID- 25849357
TI  - Pulse and entrainment to non-isochronous auditory stimuli: the case of north
      Indian alap.
AB  - Pulse is often understood as a feature of a (quasi-) isochronous event sequence
      that is picked up by an entrained subject. However, entrainment does not only
      occur between quasi-periodic rhythms. This paper demonstrates the expression of
      pulse by subjects listening to non-periodic musical stimuli and investigates the
      processes behind this behaviour. The stimuli are extracts from the introductory
      sections of North Indian (Hindustani) classical music performances (alap, jor and
      jhala). The first of three experiments demonstrates regular motor responses to
      both irregular alap and more regular jor sections: responses to alap appear
      related to individual spontaneous tempi, while for jor they relate to the
      stimulus event rate. A second experiment investigated whether subjects respond to
      average periodicities of the alap section, and whether their responses show phase
      alignment to the musical events. In the third experiment we investigated
      responses to a broader sample of performances, testing their relationship to
      spontaneous tempo, and the effect of prior experience with this music. Our
      results suggest an entrainment model in which pulse is understood as the
      experience of one's internal periodicity: it is not necessarily linked to
      temporally regular, structured sensory input streams; it can arise spontaneously
      through the performance of repetitive motor actions, or on exposure to event
      sequences with rather irregular temporal structures. Greater regularity in the
      external event sequence leads to entrainment between motor responses and stimulus
      sequence, modifying subjects' internal periodicities in such a way that they are
      either identical or harmonically related to each other. This can be considered as
      the basis for shared (rhythmic) experience and may be an important process
      supporting 'social' effects of temporally regular music. 

PMID- 25849359
TI  - Efficient and anonymous two-factor user authentication in wireless sensor
      networks: achieving user anonymity with lightweight sensor computation.
AB  - A smart-card-based user authentication scheme for wireless sensor networks
      (hereafter referred to as a SCA-WSN scheme) is designed to ensure that only users
      who possess both a smart card and the corresponding password are allowed to gain
      access to sensor data and their transmissions. Despite many research efforts in
      recent years, it remains a challenging task to design an efficient SCA-WSN scheme
      that achieves user anonymity. The majority of published SCA-WSN schemes use only
      lightweight cryptographic techniques (rather than public-key cryptographic
      techniques) for the sake of efficiency, and have been demonstrated to suffer from
      the inability to provide user anonymity. Some schemes employ elliptic curve
      cryptography for better security but require sensors with strict resource
      constraints to perform computationally expensive scalar-point multiplications;
      despite the increased computational requirements, these schemes do not provide
      user anonymity. In this paper, we present a new SCA-WSN scheme that not only
      achieves user anonymity but also is efficient in terms of the computation loads
      for sensors. Our scheme employs elliptic curve cryptography but restricts its use
      only to anonymous user-to-gateway authentication, thereby allowing sensors to
      perform only lightweight cryptographic operations. Our scheme also enjoys
      provable security in a formal model extended from the widely accepted Bellare
      Pointcheval-Rogaway (2000) model to capture the user anonymity property and
      various SCA-WSN specific attacks (e.g., stolen smart card attacks, node capture
      attacks, privileged insider attacks, and stolen verifier attacks). 

PMID- 25849358
TI  - Longitudinal neurostimulation in older adults improves working memory.
AB  - An increasing concern affecting a growing aging population is working memory (WM)
      decline. Consequently, there is great interest in improving or stabilizing WM,
      which drives expanded use of brain training exercises. Such regimens generally
      result in temporary WM benefits to the trained tasks but minimal transfer of
      benefit to untrained tasks. Pairing training with neurostimulation may stabilize
      or improve WM performance by enhancing plasticity and strengthening WM-related
      cortical networks. We tested this possibility in healthy older adults.
      Participants received 10 sessions of sham (control) or active (anodal, 1.5 mA)
      tDCS to the right prefrontal, parietal, or prefrontal/parietal (alternating)
      cortices. After ten minutes of sham or active tDCS, participants performed verbal
      and visual WM training tasks. On the first, tenth, and follow-up sessions,
      participants performed transfer WM tasks including the spatial 2-back, Stroop,
      and digit span tasks. The results demonstrated that all groups benefited from WM
      training, as expected. However, at follow-up 1-month after training ended, only
      the participants in the active tDCS groups maintained significant improvement.
      Importantly, this pattern was observed for both trained and transfer tasks. These
      results demonstrate that tDCS-linked WM training can provide long-term benefits
      in maintaining cognitive training benefits and extending them to untrained tasks.

PMID- 25849360
TI  - Unraveling the conformational landscape of triallyl phosphate: matrix isolation
      infrared spectroscopy and density functional theory computations.
AB  - The conformations of triallyl phosphate (TAP) were studied using matrix isolation
      infrared spectroscopy and density functional theory (DFT) calculations. TAP was
      trapped in N2, Ar, and Xe matrixes at 12 K using an effusive source and the
      resultant infrared spectra recorded. The computational analysis on conformers of
      TAP is a challenging problem due to the presence of the large number of
      conformations. To simplify this problem, conformational analysis was performed on
      prototypical molecules such as dimethyl allyl phosphate (DMAP) and diallyl methyl
      phosphate (DAMP), to systematically arrive at the conformations of TAP. The above
      methodology discerned 131 conformations for TAP, which were found to contribute
      to the room temperature population. The computations were performed using B3LYP/6
      311++G(d,p) level of theory. Vibrational wavenumber calculations were performed
      for the various conformers to assign the experimental infrared features of TAP,
      trapped in solid N2, Ar, and Xe matrixes. 

PMID- 25849361
TI  - Presence, objecthood, and the phenomenology of predictive perception.
AB  - Can perceptual presence be explained by counterfactually-rich predictive models
      linking perception and action? Considering an unusually rich range of responses
      to this idea has led me to (1) re-emphasize the core conceptual commitment of
      "predictive processing of sensorimotor contingencies" (PPSMC) to predictive model
      based perception, (2) reconsider the relationship between presence and
      objecthood, and (3) refine the phenomenological target by differentiating between
      perceptual presence and the phenomenology of absence-of-presence, or "phenomenal
      unreality." It turns out that this requires blue-sky thinking. 

PMID- 25849362
TI  - Compound heterozygous mutation of Rag1 leading to Omenn syndrome.
AB  - Omenn syndrome is a primary immunodeficiency disorder, featuring susceptibility
      to infections and autoreactive T cells and resulting from defective genomic
      rearrangement of genes for the T cell and B cell receptors. The most frequent
      etiologies are hypomorphic mutations in "non-core" regions of the Rag1 or Rag2
      genes, the protein products of which are critical members of the cellular
      apparatus for V(D)J recombination. In this report, we describe an infant with
      Omenn syndrome with a previously unreported termination mutation (p.R142*) in
      Rag1 on one allele and a partially characterized substitution mutation (p.V779M)
      in a "core" region of the other Rag1 allele. Using a cellular recombination
      assay, we found that while the p.R142* mutation completely abolished V(D)J
      recombination activity, the p.V779M mutation conferred a severe, but not total,
      loss of V(D)J recombination activity. The recombination defect of the V779 mutant
      was not due to overall misfolding of Rag1, however, as this mutant supported wild
      type levels of V(D)J cleavage. These findings provide insight into the role of
      this poorly understood region of Rag1 and support the role of Rag1 in a post
      cleavage stage of recombination. 

PMID- 25849363
TI  - The interaction of Arabidopsis with Piriformospora indica shifts from initial
      transient stress induced by fungus-released chemical mediators to a mutualistic
      interaction after physical contact of the two symbionts.
AB  - BACKGROUND: Piriformospora indica, an endophytic fungus of Sebacinales, colonizes
      the roots of many plant species including Arabidopsis thaliana. The symbiotic
      interaction promotes plant performance, growth and resistance/tolerance against
      abiotic and biotic stress. RESULTS: We demonstrate that exudated compounds from
      the fungus activate stress and defense responses in the Arabidopsis roots and
      shoots before the two partners are in physical contact. They induce stomata
      closure, stimulate reactive oxygen species (ROS) production, stress-related
      phytohormone accumulation and activate defense and stress genes in the roots
      and/or shoots. Once a physical contact is established, the stomata re-open, ROS
      and phytohormone levels decline, and the number and expression level of
      defense/stress-related genes decreases. CONCLUSIONS: We propose that exudated
      compounds from P. indica induce stress and defense responses in the host. Root
      colonization results in the down-regulation of defense responses and the
      activation of genes involved in promoting plant growth, metabolism and
      performance.

PMID- 25849364
TI  - The association between chronic kidney disease and diabetic retinopathy: the
      Korea National Health and Nutrition Examination Survey 2008-2010.
AB  - PURPOSE: To explore the relationship between chronic kidney disease and diabetic
      retinopathy in a representative population of Korean diabetic adults. METHODS: We
      analyzed data from the Korea National Health and Nutrition Examination Surveys
      (2008-2010). A total of 15,409 individuals (weighted frequency, 32,168,636) aged
      19 and over who completed ophthalmologic and renal functional examinations were
      evaluated. Chronic kidney disease (CKD) was defined as an estimated glomerular
      filtration rate of < 60 ml/min/1.73 m2 or proteinuria greater than 1+. Seven
      standard photographs from the Early Treatment for Diabetic Retinopathy Study were
      obtained from each eye after pharmacological pupil dilatation. Diabetic
      retinopathy (DR) was defined as the presence of 1 or more retinal microaneurysms
      or retinal blot hemorrhages with or without more severe lesions. Vision
      threatening diabetic retinopathy (VTDR) was defined as the presence of a
      clinically significant macular edema (CSME) or proliferative diabetic
      retinopathy. RESULTS: CKD was significantly associated with DR and VTDR (odds
      ratio (OR), 95% confidence interval (CI); 2.49(1.43-4.35) and 3.74(1.56-8.95),
      respectively) in the diabetic population. After controlling for confounders,
      however, CKD was significantly associated only with DR [adjusted OR (aOR), 95%
      CI; 2.34(1.04-5.28)]. In the subgroup analysis for CKD, only proteinuria was
      significantly associated with DR and VTDR (aOR, 95% CI; 4.56(1.51-13.77) and
      5.61(1.06-29.87), respectively) in this population. CONCLUSIONS: Our results show
      that CKD appears to be associated with DR and VTDR in a Korean diabetic
      population. In particular, proteinuria, not decreased eGFR, is more significantly
      associated with DR or VTDR.

PMID- 25849365
TI  - Cofactor specificity motifs and the induced fit mechanism in class I ketol-acid
      reductoisomerases.
AB  - Although most sequenced members of the industrially important ketol-acid
      reductoisomerase (KARI) family are class I enzymes, structural studies to date
      have focused primarily on the class II KARIs, which arose through domain
      duplication. In the present study, we present five new crystal structures of
      class I KARIs. These include the first structure of a KARI with a six-residue
      beta2alphaB (cofactor specificity determining) loop and an NADPH phosphate
      binding geometry distinct from that of the seven- and 12-residue loops. We also
      present the first structures of naturally occurring KARIs that utilize NADH as
      cofactor. These results show insertions in the specificity loops that confounded
      previous attempts to classify them according to loop length. Lastly, we explore
      the conformational changes that occur in class I KARIs upon binding of cofactor
      and metal ions. The class I KARI structures indicate that the active sites close
      upon binding NAD(P)H, similar to what is observed in the class II KARIs of rice
      and spinach and different from the opening of the active site observed in the
      class II KARI of Escherichia coli. This conformational change involves a decrease
      in the bending of the helix that runs between the domains and a rearrangement of
      the nicotinamide-binding site. 

PMID- 25849366
TI  - Mechanism of action studies of lomaiviticin A and the monomeric lomaiviticin
      aglycon. Selective and potent activity toward DNA double-strand break repair
      deficient cell lines.
AB  - (-)-Lomaiviticin A (1) and the monomeric lomaiviticin aglycon [aka: (-)-MK7-206,
      (3)] are cytotoxic agents that induce double-strand breaks (DSBs) in DNA. Here we
      elucidate the cellular responses to these agents and identify synthetic lethal
      interactions with specific DNA repair factors. Toward this end, we first
      characterized the kinetics of DNA damage by 1 and 3 in human chronic myelogenous
      leukemia (K562) cells. DSBs are rapidly induced by 3, reaching a maximum at 15
      min post addition and are resolved within 4 h. By comparison, DSB production by 1
      requires 2-4 h to achieve maximal values and >8 h to achieve resolution. As
      evidenced by an alkaline comet unwinding assay, 3 induces extensive DNA damage,
      suggesting that the observed DSBs arise from closely spaced single-strand breaks
      (SSBs). Both 1 and 3 induce ataxia telangiectasia mutated- (ATM-) and DNA
      dependent protein kinase- (DNA-PK-) dependent production of phospho-SER139
      histone H2AX (gammaH2AX) and generation of p53 binding protein 1 (53BP1) foci in
      K562 cells within 1 h of exposure, which is indicative of activation of
      nonhomologous end joining (NHEJ) and homologous recombination (HR) repair. Both
      compounds also lead to ataxia telangiectasia and Rad3-related- (ATR-) dependent
      production of gammaH2AX at later time points (6 h post addition), which is
      indicative of replication stress. 3 is also shown to induce apoptosis. In accord
      with these data, 1 and 3 were found to be synthetic lethal with certain mutations
      in DNA DSB repair. 1 potently inhibits the growth of breast cancer type 2, early
      onset- (BRCA2-) deficient V79 Chinese hamster lung fibroblast cell line
      derivative (VC8), and phosphatase and tensin homologue deleted on chromosome ten-
      (PTEN-) deficient human glioblastoma (U251) cell lines, with LC50 values of 1.5
      +/- 0.5 and 2.0 +/- 0.6 pM, respectively, and selectivities of >11.6 versus the
      isogenic cell lines transfected with and expressing functional BRCA2 and PTEN
      genes. 3 inhibits the growth of the same cell lines with LC50 values of 6.0 +/-
      0.5 and 11 +/- 4 nM and selectivities of 84 and 5.1, for the BRCA2 and PTEN
      mutants, respectively. These data argue for the evaluation of these agents as
      treatments for tumors that are deficient in BRCA2 and PTEN, among other DSB
      repair factors. 

PMID- 25849368
TI  - Single-layer ionic conduction on carboxyl-terminated silane monolayers patterned
      by constructive lithography.
AB  - Ionic transport plays a central role in key technologies relevant to energy, and
      information processing and storage, as well as in the implementation of
      biological functions in living organisms. Here, we introduce a supramolecular
      strategy based on the non-destructive chemical patterning of a highly ordered
      self-assembled monolayer that allows the reproducible fabrication of ion
      conducting surface patterns (ion-conducting channels) with top -COOH functional
      groups precisely definable over the full range of length scales from nanometre to
      centimetre. The transport of a single layer of selected metal ions and the
      electrochemical processes related to their motion may thus be confined to
      predefined surface paths. As a generic solid ionic conductor that can accommodate
      different mobile ions in the absence of any added electrolyte, these ion
      conducting channels exhibit bias-induced competitive transport of different ionic
      species. This approach offers unprecedented opportunities for the realization of
      designed ion-conducting systems with nanoscale control, beyond the inherent
      limitations posed by available ionic materials. 

PMID- 25849367
TI  - Effects of the I559P gp41 change on the conformation and function of the human
      immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer.
AB  - The mature human immunodeficiency virus (HIV-1) envelope glycoprotein (Env)
      trimer is produced by proteolytic cleavage of a precursor and consists of three
      gp120 exterior and three gp41 transmembrane subunits. The metastable Env complex
      is induced to undergo conformational changes required for virus entry by the
      binding of gp120 to the receptors, CD4 and CCR5/CXCR4. An isoleucine-to-proline
      change (I559P) in the gp41 ectodomain has been used to stabilize soluble forms of
      HIV-1 Env trimers for structural characterization and for use as immunogens. In
      the native membrane-anchored HIV-1BG505 Env, the I559P change modestly decreased
      proteolytic maturation, increased the non-covalent association of gp120 with the
      Env trimer, and resulted in an Env conformation distinctly different from that of
      the wild-type HIV-1BG505 Env. Compared with the wild-type Env, the I559P Env was
      recognized inefficiently by polyclonal sera from HIV-1-infected individuals, by
      several gp41-directed antibodies, by some antibodies against the CD4-binding site
      of gp120, and by antibodies that preferentially recognize the CD4-bound Env. Some
      of the gp120-associated antigenic differences between the wild-type HIV-1BG505
      Env and the I559P mutant were compensated by the SOS disulfide bond between gp120
      and gp41, which has been used to stabilize cleaved soluble Env trimers.
      Nonetheless, regardless of the presence of the SOS changes, Envs with proline 559
      were recognized less efficiently than Envs with isoleucine 559 by the VRC01
      neutralizing antibody, which binds the CD4-binding site of gp120, and the PGT151
      neutralizing antibody, which binds a hybrid gp120-gp41 epitope. The I559P change
      completely eliminated the ability of the HIV-1BG505 Env to mediate cell-cell
      fusion and virus entry, and abolished the capacity of the SOS Env to support
      virus infection in the presence of a reducing agent. These results suggest that
      differences exist between the quaternary structures of functional Env spikes and
      I559P Envs. 

PMID- 25849369
TI  - Flexible n-type thermoelectric materials by organic intercalation of layered
      transition metal dichalcogenide TiS2.
AB  - Organic semiconductors are attracting increasing interest as flexible
      thermoelectric materials owing to material abundance, easy processing and low
      thermal conductivity. Although progress in p-type polymers and composites has
      been reported, their n-type counterpart has fallen behind owing to difficulties
      in n-type doping of organic semiconductors. Here, we present an approach to
      synthesize n-type flexible thermoelectric materials through a facile
      electrochemical intercalation method, fabricating a hybrid superlattice of
      alternating inorganic TiS2 monolayers and organic cations. Electrons were
      externally injected into the inorganic layers and then stabilized by organic
      cations, providing n-type carriers for current and energy transport. An
      electrical conductivity of 790 S cm(-1) and a power factor of 0.45 mW m(-1) K(-2)
      were obtained for a hybrid superlattice of TiS2/[(hexylammonium)x(H2O)y(DMSO)z],
      with an in-plane lattice thermal conductivity of 0.12 +/- 0.03 W m(-1) K(-1),
      which is two orders of magnitude smaller than the thermal conductivities of the
      single-layer and bulk TiS2. High power factor and low thermal conductivity
      contributed to a thermoelectric figure of merit, ZT, of 0.28 at 373 K, which
      might find application in wearable electronics. 

PMID- 25849370
TI  - Stabilizing triplet excited states for ultralong organic phosphorescence.
AB  - The control of the emission properties of synthetic organic molecules through
      molecular design has led to the development of high-performance optoelectronic
      devices with tunable emission colours, high quantum efficiencies and efficient
      energy/charge transfer processes. However, the task of generating excited states
      with long lifetimes has been met with limited success, owing to the ultrafast
      deactivation of the highly active excited states. Here, we present a design rule
      that can be used to tune the emission lifetime of a wide range of luminescent
      organic molecules, based on effective stabilization of triplet excited states
      through strong coupling in H-aggregated molecules. Our experimental data revealed
      that luminescence lifetimes up to 1.35 s, which are several orders of magnitude
      longer than those of conventional organic fluorophores, can be realized under
      ambient conditions. These results outline a fundamental principle to design
      organic molecules with extended lifetimes of excited states, providing a major
      step forward in expanding the scope of organic phosphorescence applications. 

PMID- 25849371
TI  - Gene expression profiles associated with pediatric relapsed AML.
AB  - Development of relapse remains a problem for further improvements in the survival
      of pediatric AML patients. While virtually all patients show a good response to
      initial treatment, more patients respond poorly when treated at relapse. The
      cellular characteristics of leukemic blast cells that allow survival of initial
      treatment, relapse development and subsequent resistance to salvage treatment
      remain largely elusive. Therefore, we studied if leukemic blasts at relapse
      biologically resemble their initial diagnosis counterparts. We performed
      microarray gene expression profiling on paired initial and relapse samples of 23
      pediatric AML patients. In 11 out of 23 patients, gene expression profiles of
      initial and corresponding relapse samples end up in different clusters in
      unsupervised analysis, indicating altered gene expression profiles. In addition,
      shifts in type I/II mutational status were found in 5 of these 11 patients, while
      shifts were found in 3 of the remaining 12 patients. Although differentially
      expressed genes varied between patients, they were commonly related to
      hematopoietic differentiation, encompassed genes involved in chromatin remodeling
      and showed associations with similar transcription factors. The top five were
      CEBPA, GFI1, SATB1, KLF2 and TBP. In conclusion, the leukemic blasts at relapse
      are biologically different from their diagnosis counterparts. These differences
      may be exploited for further development of novel treatment strategies. 

PMID- 25849372
TI  - Apolipoprotein-A1 as a damage-associated molecular patterns protein in
      osteoarthritis: ex vivo and in vitro pro-inflammatory properties.
AB  - Osteoarthritis (OA) is associated with a local inflammatory process. Dyslipidemia
      is known to be an underlying cause for the development of OA. Therefore, lipid
      and inflammatory levels were quantified ex vivo in blood and synovial fluid of OA
      patients (n=29) and compared to those of rheumatoid arthritis (RA) patients
      (n=27) or healthy volunteers (HV) (n=35). The role of apolipoprotein A-I (ApoA1)
      was investigated in vitro on inflammatory parameters using human joint cells
      isolated from cartilage and synovial membrane obtained from OA patients after
      joint replacement. Cells were stimulated with ApoA1 in the presence or not of
      serum amyloid A (SAA) protein and/or lipoproteins (LDL and HDL) at physiological
      concentration observed in OA synovial fluid. In our ex vivo study, ApoA1, LDL-C
      and total cholesterol levels were strongly correlated to each other inside the OA
      joint cavity whereas same levels were not or weakly correlated to their
      corresponding serum levels. In OA synovial fluid, ApoA1 was not as strongly
      correlated to HDL as observed in OA serum or in RA synovial fluid, suggesting a
      dissociative level between ApoA1 and HDL in OA synovial fluid. In vitro, ApoA1
      induced IL-6, MMP-1 and MMP-3 expression by primary chondrocytes and fibroblast
      like synoviocytes through TLR4 receptor. HDL and LDL attenuated joint
      inflammatory response induced by ApoA1 and SAA in a ratio dependent manner. In
      conclusion, a dysregulated lipidic profile in the synovial fluid of OA patients
      was observed and was correlated with inflammatory parameters in the OA joint
      cavity. Pro-inflammatory properties of ApoA1 were confirmed in vitro. 

PMID- 25849373
TI  - Systematic functional profiling of transcription factor networks in Cryptococcus
      neoformans.
AB  - Cryptococcus neoformans causes life-threatening meningoencephalitis in humans,
      but its overall biological and pathogenic regulatory circuits remain elusive,
      particularly due to the presence of an evolutionarily divergent set of
      transcription factors (TFs). Here, we report the construction of a high-quality
      library of 322 signature-tagged gene-deletion strains for 155 putative TF genes
      previously predicted using the DNA-binding domain TF database, and examine their
      in vitro and in vivo phenotypic traits under 32 distinct growth conditions. At
      least one phenotypic trait is exhibited by 145 out of 155 TF mutants (93%) and
      ~85% of them (132/155) are functionally characterized for the first time in this
      study. The genotypic and phenotypic data for each TF are available in the C.
      neoformans TF phenome database (http://tf.cryptococcus.org). In conclusion, our
      phenome-based functional analysis of the C. neoformans TF mutant library provides
      key insights into transcriptional networks of basidiomycetous fungi and human
      fungal pathogens. 

PMID- 25849375
TI  - Analysis of bias in measurements of potassium, sodium and hemoglobin by an
      emergency department-based blood gas analyzer relative to hospital laboratory
      autoanalyzer results.
AB  - OBJECTIVE: The emergency departments (EDs) of Chinese hospitals are gradually
      being equipped with blood gas machines. These machines, along with the
      measurement of biochemical markers by the hospital laboratory, facilitate the
      care of patients with severe conditions who present to the ED. However,
      discrepancies have been noted between the Arterial Blood Gas (ABG) analyzers in
      the ED and the hospital laboratory autoanalyzer in relation to electrolyte and
      hemoglobin measurements. The present study was performed to determine whether the
      ABG and laboratory measurements of potassium, sodium, and hemoglobin levels are
      equivalent, and whether ABG analyzer results can be used to guide clinical care
      before the laboratory results become available. MATERIALS AND METHODS: Study
      power analyses revealed that 200 consecutive patients who presented to our ED
      would allow this prospective single-center cohort study to detect significant
      differences between ABG- and laboratory-measured potassium, sodium, and
      hemoglobin levels. Paired arterial and venous blood samples were collected within
      30 minutes. Arterial blood samples were measured in the ED by an ABL 90 FLEX
      blood gas analyzer. The biochemistry and blood cell counts of the venous samples
      were measured in the hospital laboratory. The potassium, sodium, and hemoglobin
      concentrations obtained by both methods were compared by using paired Student's t
      test, Spearman's correlation, Bland-Altman plots, and Deming regression. RESULTS:
      The mean ABG and laboratory potassium values were 3.77+/-0.44 and 4.2+/-0.55,
      respectively (P<0.0001). The mean ABG and laboratory sodium values were 137.89+/
      5.44 and 140.93+/-5.50, respectively (P<0.0001). The mean ABG and laboratory
      Hemoglobin values were 12.28+/-2.62 and 12.35+/-2.60, respectively (P = 0.24).
      CONCLUSION: Although there are the statistical difference and acceptable biases
      between ABG- and laboratory-measured potassium and sodium, the biases do not
      exceed USCLIA-determined limits. In parallel, there are no statistical
      differences and biases beyond USCLIA-determined limits between ABG- and
      laboratory-measured hemoglobin. Therefore, all three variables measured by ABG
      were reliable.

PMID- 25849374
TI  - Transcriptional profiling of ectoderm specification to keratinocyte fate in human
      embryonic stem cells.
AB  - In recent years, several studies have shed light into the processes that regulate
      epidermal specification and homeostasis. We previously showed that a broad
      spectrum gamma-secretase inhibitor DAPT promoted early keratinocyte specification
      in human embryonic stem cells triggered to undergo ectoderm specification. Here,
      we show that DAPT accelerates human embryonic stem cell differentiation and
      induces expression of the ectoderm protein AP2. Furthermore, we utilize RNA
      sequencing to identify several candidate regulators of ectoderm specification
      including those involved in epithelial and epidermal development in human
      embryonic stem cells. Genes associated with transcriptional regulation and growth
      factor activity are significantly enriched upon DAPT treatment during
      specification of human embryonic stem cells to the ectoderm lineage. The human
      ectoderm cell signature identified in this study contains several genes expressed
      in ectodermal and epithelial tissues. Importantly, these genes are also
      associated with skin disorders and ectodermal defects, providing a platform for
      understanding the biology of human epidermal keratinocyte development under
      diseased and homeostatic conditions. 

PMID- 25849376
TI  - Proteomic analysis of mice fed methionine and choline deficient diet reveals
      marker proteins associated with steatohepatitis.
AB  - The mechanisms underlying the progression of simple steatosis to steatohepatitis
      are yet to be elucidated. To identify the proteins involved in the development of
      liver tissue inflammation, we performed comparative proteomic analysis of non
      alcoholic steatohepatitis (NASH). Mice fed a methionine and choline deficient
      diet (MCD) developed hepatic steatosis characterized by increased free fatty acid
      (FFA) and triglyceride levels as well as alpha-SMA. Two-dimensional proteomic
      analysis revealed that the change from the normal diet to the MCD diet affected
      the expressions of 50 proteins. The most-pronounced changes were observed in the
      expression of proteins involved in Met metabolism and oxidative stress, most of
      which were significantly downregulated in NASH model animals. Peroxiredoxin (Prx)
      is the most interesting among the modulated proteins identified in this study. In
      particular, cross-regulated Prx1 and Prx6 are likely to participate in cellular
      defense against the development of hepatitis. Thus, these Prx isoforms may be a
      useful new marker for early stage steatohepatitis. Moreover, curcumin treatment
      results in alleviation of the severity of hepatic inflammation in
      steatohepatitis. Notably, curcumin administration in MCD-fed mice dramatically
      reduced CYP2E1 as well as Prx1 expression, while upregulating Prx6 expression.
      These findings suggest that curcumin may have a protective role against MCD fed
      induced oxidative stress. 

PMID- 25849377
TI  - Suppressor of cytokine signaling (SOCS) genes are silenced by DNA
      hypermethylation and histone deacetylation and regulate response to radiotherapy
      in cervical cancer cells.
AB  - Suppressor of cytokine signaling (SOCS) family is an important negative regulator
      of cytokine signaling and deregulation of SOCS has been involved in many types of
      cancer. All cervical cancer cell lines tested showed lower expression of SOCS1,
      SOCS3, and SOCS5 than normal tissue or cell lines. The immunohistochemistry
      result for SOCS proteins in human cervical tissue also confirmed that normal
      tissue expressed higher level of SOCS proteins than neighboring tumor. Similar to
      the regulation of SOCS in other types of cancer, DNA methylation contributed to
      SOCS1 downregulation in CaSki, ME-180, and HeLa cells. However, the expression of
      SOCS3 or SOCS5 was not recovered by the inhibition of DNA methylation. Histone
      deacetylation may be another regulatory mechanism involved in SOCS1 and SOCS3
      expression, however, SOCS5 expression was neither affected by DNA methylation nor
      histone deacetylation. Ectopic expression of SOCS1 or SOCS3 conferred
      radioresistance to HeLa cells, which implied SOCS signaling regulates the
      response to radiation in cervical cancer. In this study, we have shown that SOCS
      expression repressed by, in part, epigenetically and altered SOCS1 and SOCS3
      expression could contribute to the radiosensitive phenotype in cervical cancer. 

PMID- 25849378
TI  - Haberlea rhodopensis: pharmaceutical and medical potential as a food additive.
AB  - This review discusses the potential of Haberlea rhodopensis as a food additive.
      The following are described: plant distribution, reproduction, cultivation,
      propagation and resurrection properties; extraction, isolation and screening of
      biologically active compounds; metabolite changes during dehydration;
      phytotherapy-related properties such as antioxidant potential and free radical
      scavenging activities, antioxidant skin effect, antibacterial activity, cytotoxic
      activity and cancer-modulating effect, radioprotective effect, chemoprotective
      effect, immunologic effect; present use in homoeopathy and cosmetics,
      pharmacological and economical importance; perspectives based on the
      ethnobotanical data for medicinal, cosmetic or ritual attributes. H. rhodopensis
      showed unique medical and pharmaceutical potential, related to antioxidant,
      antimicrobial, antimutagenic, anticancer, radioprotective, chemoprotective and
      immunological properties. H. rhodopensis extracts lack any cytotoxic activity and
      could be used in phytotherapy. The metabolic profiling of H. rhodopensis extracts
      revealed the presence of biologically active compounds, possessing antiradical
      and other physiological activities, useful for design of in vitro synthesised
      analogues and drugs. 

PMID- 25849379
TI  - Lgr5+ cells regenerate hair cells via proliferation and direct
      transdifferentiation in damaged neonatal mouse utricle.
AB  - Recruitment of endogenous progenitors is critical during tissue repair. The inner
      ear utricle requires mechanosensory hair cells (HCs) to detect linear
      acceleration. After damage, non-mammalian utricles regenerate HCs via both
      proliferation and direct transdifferentiation. In adult mammals, limited
      transdifferentiation from unidentified progenitors occurs to regenerate
      extrastriolar Type II HCs. Here we show that HC damage in neonatal mouse utricle
      activates the Wnt target gene Lgr5 in striolar supporting cells. Lineage tracing
      and time-lapse microscopy reveal that Lgr5+ cells transdifferentiate into HC-like
      cells in vitro. In contrast to adults, HC ablation in neonatal utricles in vivo
      recruits Lgr5+ cells to regenerate striolar HCs through mitotic and
      transdifferentiation pathways. Both Type I and II HCs are regenerated, and
      regenerated HCs display stereocilia and synapses. Lastly, stabilized beta-catenin
      in Lgr5+ cells enhances mitotic activity and HC regeneration. Thus Lgr5 marks Wnt
      regulated, damage-activated HC progenitors and may help uncover factors driving
      mammalian HC regeneration. 

PMID- 25849381
TI  - Comparison of astigmatic correction after femtosecond lenticule extraction and
      small-incision lenticule extraction for myopic astigmatism.
AB  - PURPOSE: To compare postoperative astigmatic correction between femtosecond
      lenticule extraction (FLEx) and small-incision lenticule extraction (SMILE) in
      eyes with myopic astigmatism. METHODS: We examined 26 eyes of 26 patients
      undergoing FLEx and 26 eyes of 26 patients undergoing SMILE to correct myopic
      astigmatism (manifest astigmatism of 1 diopter (D) or more). Visual acuity,
      cylindrical refraction, the predictability of the astigmatic correction, and the
      astigmatic vector components using Alpin's method, were compared between the two
      groups 3 months postoperatively. RESULTS: We found no statistically significant
      difference in manifest cylindrical refraction (p=0.74) or in the percentage of
      eyes within +/- 0.50 D of their refraction (p=0.47) after the two surgical
      procedures. Moreover, no statistically significant difference was detected
      between the groups in astigmatic vector components, namely, surgically induced
      astigmatism (0.80), target induced astigmatism (p=0.87), astigmatic correction
      index (p=0.77), angle of error (p=0.24), difference vector (p=0.76), index of
      success (p=0.91), flattening effect (p=0.79), and flattening index (p=0.84).
      CONCLUSIONS: Both FLEx and SMILE procedures are essentially equivalent in
      correcting myopic astigmatism using vector analysis, suggesting that the lifting
      or non-lifting of the flap does not significantly affect astigmatic outcomes
      after these surgical procedures.

PMID- 25849380
TI  - Activation of TRPV1 channel by dietary capsaicin improves visceral fat remodeling
      through connexin43-mediated Ca2+ influx.
AB  - BACKGROUND: The prevalence of obesity has dramatically increased worldwide and
      has attracted rising attention, but the mechanism is still unclear. Previous
      studies revealed that transient receptor potential vanilloid 1 (TRPV1) channels
      take part in weight loss by enhancing intracellular Ca2+ levels. However, the
      potential mechanism of the effect of dietary capsaicin on obesity is not
      completely understood. Ca2+ transfer induced by connexin43 (Cx43) molecules
      between coupled cells takes part in adipocyte differentiation. Whether TRPV1
      evoked alterations in Cx43-mediated adipocyte-to-adipocyte communication play a
      role in obesity is unknown. MATERIALS AND METHODS: We investigated whether Cx43
      participated in TRPV1-mediated adipocyte lipolysis in cultured 3T3-L1
      preadipocytes and visceral adipose tissues from humans and wild-type (WT) and
      TRPV1-deficient (TRPV1-/-) mice. RESULTS: TRPV1 and Cx43 co-expressed in
      mesenteric adipose tissue. TRPV1 activation by capsaicin increased the influx of
      Ca2+ in 3T3-L1 preadipocytes and promoted cell lipolysis, as shown by Oil-red O
      staining. These effects were deficient when capsazepine, a TRPV1 antagonist, and
      18 alpha-glycyrrhetinic acid (18alpha-GA), a gap-junction inhibitor, were
      administered. Long-term chronic dietary capsaicin reduced the weights of
      perirenal, mesenteric and testicular adipose tissues in WT mice fed a high-fat
      diet. Capsaicin increased the expression levels of p-CaM, Cx43, CaMKII, PPARdelta
      and HSL in mesenteric adipose tissues from WT mice fed a high-fat diet, db/db
      mice, as well as obese humans, but these effects of capsaicin were absent in
      TRPV1-/- mice. Long-term chronic dietary capsaicin decreased the body weights and
      serum lipids of WT mice, but not TRPV1-/- mice, fed a high-fat diet. CONCLUSION:
      This study demonstrated that capsaicin activation of TRPV1-evoked increased Ca2+
      influx in Cx43-mediated adipocyte-to-adipocyte communication promotes lipolysis
      in both vitro and vivo. TRPV1 activation by dietary capsaicin improves visceral
      fat remodeling through the up-regulation of Cx43.

PMID- 25849382
TI  - The nematicidal effect of camellia seed cake on root-knot nematode Meloidogyne
      javanica of banana.
AB  - Suppression of root-knot nematodes is crucially important for maintaining the
      worldwide development of the banana industry. Growing concerns about human and
      environmental safety have led to the withdrawal of commonly used nematicides and
      soil fumigants, thus motivating the development of alternative nematode
      management strategies. In this study, Meloidogyne javanica was isolated, and the
      nematicidal effect of Camellia seed cake on this pest was investigated. The
      results showed that in dish experiments, Camellia seed cake extracts under low
      concentration (2 g/L) showed a strong nematicidal effect. After treatment for 72
      h, the eggs of M. javanica were gradually dissolved, and the intestine of the
      juveniles gradually became indistinct. Nematicidal compounds, including saponins
      identified by HPLC-ESI-MS and 8 types of volatile compounds identified by GC-MS,
      exhibited effective nematicidal activities, especially 4-methylphenol. The pot
      experiments demonstrated that the application of Camellia seed cake suppressed M.
      javanica, and promoted the banana plant growth. This study explored an effective
      nematicidal agent for application in soil and revealed its potential mechanism of
      nematode suppression. 

PMID- 25849384
TI  - Enhanced Photoreduction CO2 Activity over Direct Z-Scheme alpha-Fe2O3/Cu2O
      Heterostructures under Visible Light Irradiation.
AB  - Hematite-cuprous oxide (alpha-Fe2O3/Cu2O) nanocomposites are synthesized based on
      the design of Z-scheme photocatalyst for CO2 reduction. The band structure for
      the typical Fe2O3/Cu2O (with 1:1 mole ratio) is characterized by UV-vis
      reflectance spectroscopy and X-ray/ultraviolet photoelectron spectroscopy, and
      its heterojunction is determined to be Type II band alignment. The photoreduction
      CO2 activities of the heterostructures are investigated in the presence of water
      vapor. The CO yields are changed with Fe/Cu mole ratio, and the maximal CO yield
      attains 5.0 MUmol.g cat(-1) after 3 h of visible-light irradiation. Besides the
      effect of light wavelength, H2O/CO2 molar ratio and temperature on the products
      is studied. The selectivity of the prepared catalysts is tunable by modulating
      the light wavelength. The reaction mechanism is proposed and further confirmed
      experimentally. The results gained herein may provide some insights into the
      design of Z-scheme photocatalysts for CO2 reduction. 

PMID- 25849383
TI  - Is a cancer diagnosis associated with subsequent risk of transient global
      amnesia?
AB  - BACKGROUND: Psychological stress has been associated with transient global
      amnesia (TGA). Whether a cancer diagnosis, a severely stressful life event, is
      associated with subsequent risk of TGA has not been studied. METHODS: Based on
      the Swedish Cancer Register and Patient Register, we conducted a prospective
      cohort study including 5,365,608 Swedes at age 30 and above during 2001-2009 to
      examine the relative risk of TGA among cancer patients, as compared to cancer
      free individuals. Incidence rate ratios (IRRs) and their 95% confidence intervals
      (CIs) derived from Poisson regression were used as estimates of the association
      between cancer diagnosis and the risk of TGA. RESULTS: During the study 322,558
      individuals (6.01%) received a first diagnosis of cancer. We identified 210 cases
      of TGA among the cancer patients (incidence rate, 0.22 per 1000 person-years) and
      4,887 TGA cases among the cancer-free individuals (incidence rate, 0.12 per 1000
      person-years). Overall, after adjustment for age, sex, calendar year,
      socioeconomic status, education and civil status, cancer patients had no
      increased risk of TGA than the cancer-free individuals (IRR, 0.99; 95% CI, 0.86
      1.13). The IRRs did not differ over time since cancer diagnosis or across
      individual cancer types. The null association was neither modified by sex,
      calendar period or age. CONCLUSION: Our study did not provide support for the
      hypothesis that patients with a new diagnosis of cancer display a higher risk of
      TGA than cancer-free individuals.

PMID- 25849386
TI  - Structure of N-myristoyltransferase from Aspergillus fumigatus.
AB  - N-Myristoyltransferase (NMT) is an enzyme which translocates the 14-carbon
      saturated fatty acid myristate from myristoyl-CoA to the N-terminal glycine of
      substrate peptides. This myristoylation process is involved in protein
      modification in various eukaryotes, including animals and fungi. Furthermore,
      this enzyme has been shown to be essential to the growth of various species, such
      as Saccharomyces cerevisiae, which indicates that NMT is an attractive target for
      the development of a novel antifungal drug. In this study, the crystal structure
      of a ternary complex of NMT from Aspergillus fumigatus with S-(2-oxo)pentadecyl
      CoA, a myristoyl-CoA analogue cofactor, and a synthetic inhibitor is reported at
      a resolution of 2.1 A. The results advance the understanding of the specificity
      of NMT inhibitors and provide valuable information for structure-based drug
      design. 

PMID- 25849385
TI  - High-pressure protein crystallography of hen egg-white lysozyme.
AB  - Crystal structures of hen egg-white lysozyme (HEWL) determined under pressures
      ranging from ambient pressure to 950 MPa are presented. From 0.1 to 710 MPa, the
      molecular and internal cavity volumes are monotonically compressed. However, from
      710 to 890 MPa the internal cavity volume remains almost constant. Moreover, as
      the pressure increases to 950 MPa, the tetragonal crystal of HEWL undergoes a
      phase transition from P43212 to P43. Under high pressure, the crystal structure
      of the enzyme undergoes several local and global changes accompanied by changes
      in hydration structure. For example, water molecules penetrate into an internal
      cavity neighbouring the active site and induce an alternate conformation of one
      of the catalytic residues, Glu35. These phenomena have not been detected by
      conventional X-ray crystal structure analysis and might play an important role in
      the catalytic activity of HEWL. 

PMID- 25849388
TI  - Radiation decay of thaumatin crystals at three X-ray energies.
AB  - Radiation damage is an unavoidable obstacle in X-ray crystallographic data
      collection for macromolecular structure determination, so it is important to know
      how much radiation a sample can endure before being degraded beyond an acceptable
      limit. In the literature, the threshold at which the average intensity of all
      recorded reflections decreases to a certain fraction of the initial value is
      called the 'dose limit'. The first estimated D50 dose-limit value, at which the
      average diffracted intensity was reduced to 50%, was 20 MGy and was derived from
      observing sample decay in electron-diffraction experiments. A later X-ray study
      carried out at 100 K on ferritin protein crystals arrived at a D50 of 43 MGy, and
      recommended an intensity reduction of protein reflections to 70%, D70,
      corresponding to an absorbed dose of 30 MGy, as a more appropriate limit for
      macromolecular crystallography. In the macromolecular crystallography community,
      the rate of intensity decay with dose was then assumed to be similar for all
      protein crystals. A series of diffraction images of cryocooled (100 K) thaumatin
      crystals at identical small, 2 degrees  rotation intervals were recorded at X-ray
      energies of 6.33 , 12.66 and 19.00 keV. Five crystals were used for each
      wavelength. The decay in the average diffraction intensity to 70% of the initial
      value, for data extending to 2.45 A resolution, was determined to be about 7.5
      MGy at 6.33 keV and about 11 MGy at the two higher energies. 

PMID- 25849387
TI  - A noncanonical PWI domain in the N-terminal helicase-associated region of the
      spliceosomal Brr2 protein.
AB  - The spliceosomal RNA helicase Brr2 is required for the assembly of a
      catalytically active spliceosome on a messenger RNA precursor. Brr2 exhibits an
      unusual organization with tandem helicase units, each comprising dual RecA-like
      domains and a Sec63 homology unit, preceded by a more than 400-residue N-terminal
      helicase-associated region. Whereas recent crystal structures have provided
      insights into the molecular architecture and regulation of the Brr2 helicase
      region, little is known about the structural organization and function of its N
      terminal part. Here, a near-atomic resolution crystal structure of a PWI-like
      domain that resides in the N-terminal region of Chaetomium thermophilum Brr2 is
      presented. CD spectroscopic studies suggested that this domain is conserved in
      the yeast and human Brr2 orthologues. Although canonical PWI domains act as low
      specificity nucleic acid-binding domains, no significant affinity of the unusual
      PWI domain of Brr2 for a broad spectrum of DNAs and RNAs was detected in band
      shift assays. Consistently, the C. thermophilum Brr2 PWI-like domain, in the
      conformation seen in the present crystal structure, lacks an expanded positively
      charged surface patch as observed in at least one canonical, nucleic acid-binding
      PWI domain. Instead, in a comprehensive yeast two-hybrid screen against human
      spliceosomal proteins, fragments of the N-terminal region of human Brr2 were
      found to interact with several other spliceosomal proteins. At least one of these
      interactions, with the Prp19 complex protein SPF27, depended on the presence of
      the PWI-like domain. The results suggest that the N-terminal region of Brr2
      serves as a versatile protein-protein interaction platform in the spliceosome and
      that some interactions require or are reinforced by the PWI-like domain. 

PMID- 25849389
TI  - Structure of a double-domain phosphagen kinase reveals an asymmetric arrangement
      of the tandem domains.
AB  - Tandem duplications and fusions of single genes have led to magnificent
      expansions in the divergence of protein structures and functions over
      evolutionary timescales. One of the possible results is polydomain enzymes with
      interdomain cooperativities, few examples of which have been structurally
      characterized at the full-length level to explore their innate synergistic
      mechanisms. This work reports the crystal structures of a double-domain
      phosphagen kinase in both apo and ligand-bound states, revealing a novel
      asymmetric L-shaped arrangement of the two domains. Unexpectedly, the interdomain
      connections are not based on a flexible hinge linker but on a rigid secondary
      structure element: a long alpha-helix that tethers the tandem domains in
      relatively fixed positions. Besides the connective helix, the two domains also
      contact each other directly and form an interdomain interface in which hydrogen
      bonds and hydrophobic interactions further stabilize the L-shaped domain
      arrangement. Molecular-dynamics simulations show that the interface is generally
      stable, suggesting that the asymmetric domain arrangement crystallographically
      observed in the present study is not a conformational state simply restrained by
      crystal-packing forces. It is possible that the asymmetrically arranged tandem
      domains could provide a structural basis for further studies of the interdomain
      synergy. 

PMID- 25849390
TI  - The crystal structure of phosphorylated MAPK13 reveals common structural features
      and differences in p38 MAPK family activation.
AB  - The p38 MAP kinases (p38 MAPKs) represent an important family centrally involved
      in mediating extracellular signaling. Recent studies indicate that family members
      such as MAPK13 (p38delta) display a selective cellular and tissue expression and
      are therefore involved in specific diseases. Detailed structural studies of all
      p38 MAPK family members are crucial for the design of specific inhibitors. In
      order to facilitate such ventures, the structure of MAPK13 was determined in both
      the inactive (unphosphorylated; MAPK13) and active (dual phosphorylated;
      MAPK13/pTpY) forms. Here, the first preparation, crystallization and structure
      determination of MAPK13/pTpY are presented and the structure is compared with the
      previously reported structure of MAPK13 in order to facilitate studies for
      structure-based drug design. A comprehensive analysis of inactive versus active
      structures for the p38 MAPK family is also presented. It is found that MAPK13
      undergoes a larger interlobe configurational rearrangement upon activation
      compared with MAPK14. Surprisingly, the analysis of activated p38 MAPK structures
      (MAP12/pTpY, MAPK13/pTpY and MAPK14/pTpY) reveals that, despite a high degree of
      sequence similarity, different side chains are used to coordinate the
      phosphorylated residues. There are also differences in the rearrangement of the
      hinge region that occur in MAPK14 compared with MAPK13 which would affect
      inhibitor binding. A thorough examination of all of the active (phosphorylated)
      and inactive (unphosphorylated) p38 MAPK family member structures was performed
      to reveal a common structural basis of activation for the p38 MAP kinase family
      and to identify structural differences that may be exploited for developing
      family member-specific inhibitors. 

PMID- 25849391
TI  - Structure of Arabidopsis thaliana Rubisco activase.
AB  - The CO2-fixing enzyme ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco)
      is inactivated by the formation of dead-end complexes with inhibitory sugar
      phosphates. In plants and green algae, the ATP-dependent motor protein Rubisco
      activase restores catalytic competence by facilitating conformational changes in
      Rubisco that promote the release of the inhibitory compounds from the active
      site. Here, the crystal structure of Rubisco activase from Arabidopsis thaliana
      is presented at 2.9 A resolution. The structure reveals an AAA+ two-domain
      structure. More than 100 residues in the protein were not visible in the electron
      density map owing to conformational disorder, but were verified to be present in
      the crystal by mass spectrometry. Two sulfate ions were found in the structure.
      One was bound in the loop formed by the Walker A motif at the interface of the
      domains. A second sulfate ion was bound at the N-terminal end of the first helix
      of the C-terminal domain. The protein packs in a helical fashion in the crystal,
      as observed previously for Rubisco activase, but differences in the helical pitch
      indicate flexibility in the packing of the protein. 

PMID- 25849392
TI  - Structure of struthiocalcin-1, an intramineral protein from Struthio camelus
      eggshell, in two crystal forms.
AB  - Biomineralization is the process by which living organisms produce minerals. One
      remarkable example is the formation of eggshells in birds. Struthiocalcins
      present in the ostrich (Struthio camellus) eggshell matrix act as biosensors of
      calcite growth during eggshell formation. Here, the crystal structure of
      struthiocalcin-1 (SCA-1) is reported in two different crystal forms. The
      structure is a compact single domain with an alpha/beta fold characteristic of
      the C-type lectin family. In contrast to the related avian ovocleidin OC17, the
      electrostatic potential on the molecular surface is dominated by an acidic patch.
      Scanning electron microscopy combined with Raman spectroscopy indicates that
      these intramineral proteins (SCA-1 and SCA-2) induce calcium carbonate
      precipitation, leading to the formation of a stable form of calcite in the mature
      eggshell. Finally, the implications of these two intramineral proteins SCA-1 and
      SCA-2 in the nucleation of calcite during the formation of eggshells in ratite
      birds are discussed.

PMID- 25849393
TI  - Novel crystalline phase and first-order phase transitions of human insulin
      complexed with two distinct phenol derivatives.
AB  - The primary focus of the present work is the study of the effects that two
      ligands and the crystallization pH have on the crystalline forms of human
      insulin. For this purpose, human insulin (HI) was co-crystallized with two
      distinct phenolic derivatives: the organic ligands meta-cresol (m-cresol) and 4
      nitrophenol. The formation of polycrystalline precipitates was then followed by
      means of structural characterization of the individual specimens in terms of unit
      cell symmetry and parameters. In both cases, two different polymorphs were
      identified via X-ray powder diffraction measurements, the first of hexagonal
      symmetry (R3 space group) at higher pH values and the second of monoclinic
      symmetry (space group P21) with unit-cell parameters a = 87.4282 (5), b = 70.5020
      (3), c = 48.3180 (4) A, beta = 106.8958 (4) degrees , the latter of which to our
      knowledge has never been observed before. 

PMID- 25849394
TI  - ANS complex of St John's wort PR-10 protein with 28 copies in the asymmetric
      unit: a fiendish combination of pseudosymmetry with tetartohedral twinning.
AB  - Hyp-1, a pathogenesis-related class 10 (PR-10) protein from St John's wort
      (Hypericum perforatum), was crystallized in complex with the fluorescent probe 8
      anilino-1-naphthalene sulfonate (ANS). The highly pseudosymmetric crystal has 28
      unique protein molecules arranged in columns with sevenfold translational
      noncrystallographic symmetry (tNCS) along c and modulated X-ray diffraction with
      intensity crests at l = 7n and l = 7n +/- 3. The translational NCS is combined
      with pseudotetragonal rotational NCS. The crystal was a perfect tetartohedral
      twin, although detection of twinning was severely hindered by the pseudosymmetry.
      The structure determined at 2.4 A resolution reveals that the Hyp-1 molecules
      (packed as beta-sheet dimers) have three novel ligand-binding sites (two internal
      and one in a surface pocket), which was confirmed by solution studies. In
      addition to 60 Hyp-1-docked ligands, there are 29 interstitial ANS molecules
      distributed in a pattern that violates the arrangement of the protein molecules
      and is likely to be the generator of the structural modulation. In particular,
      whenever the stacked Hyp-1 molecules are found closer together there is an ANS
      molecule bridging them. 

PMID- 25849396
TI  - Elucidation of the crystal structure of Coriolopsis caperata laccase: restoration
      of the structure and activity of the native enzyme from the T2-depleted form by
      copper ions.
AB  - Laccases are members of a large family of multicopper oxidases that catalyze the
      oxidation of a wide range of organic and inorganic substrates accompanied by the
      reduction of dioxygen to water. A new laccase was isolated from the basidiomycete
      Coriolopsis caperata strain 0677 and its amino-acid sequence was determined.
      According to its physicochemical properties and spectroscopic features, the
      laccase from C. caperata is a high redox-potential blue laccase. Attempts to
      crystallize the native enzyme were unsuccessful. The copper type 2-depleted (T2D)
      laccase was prepared and crystallized. The structure of T2D laccase from C.
      caperata was solved at 1.6 A resolution, and attempts to reconstruct the T2
      copper centre were performed using Cu(+) and Cu(2+) ions. The structure of
      T2D+Cu(+) laccase was solved at 1.89 A resolution. It was shown that the
      T2D+Cu(+) laccase structure contained four copper ions in the active site.
      Reconstruction could not be achieved when the T2D laccase crystals were treated
      with CuSO4. 

PMID- 25849395
TI  - Structure of the N-terminal domain of the protein Expansion: an 'Expansion' to
      the Smad MH2 fold.
AB  - Gene-expression changes observed in Drosophila embryos after inducing the
      transcription factor Tramtrack led to the identification of the protein
      Expansion. Expansion contains an N-terminal domain similar in sequence to the MH2
      domain characteristic of Smad proteins, which are the central mediators of the
      effects of the TGF-beta signalling pathway. Apart from Smads and Expansion, no
      other type of protein belonging to the known kingdoms of life contains MH2
      domains. To compare the Expansion and Smad MH2 domains, the crystal structure of
      the Expansion domain was determined at 1.6 A resolution, the first structure of a
      non-Smad MH2 domain to be characterized to date. The structure displays the main
      features of the canonical MH2 fold with two main differences: the addition of an
      alpha-helical region and the remodelling of a protein-interaction site that is
      conserved in the MH2 domain of Smads. Owing to these differences, to the new
      domain was referred to as Nalpha-MH2. Despite the presence of the Nalpha-MH2
      domain, Expansion does not participate in TGF-beta signalling; instead, it is
      required for other activities specific to the protostome phyla. Based on the
      structural similarities to the MH2 fold, it is proposed that the Nalpha-MH2
      domain should be classified as a new member of the Smad/FHA superfamily. 

PMID- 25849397
TI  - A covalent adduct of MbtN, an acyl-ACP dehydrogenase from Mycobacterium
      tuberculosis, reveals an unusual acyl-binding pocket.
AB  - Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis. Access
      to iron in host macrophages depends on iron-chelating siderophores called
      mycobactins and is strongly correlated with Mtb virulence. Here, the crystal
      structure of an Mtb enzyme involved in mycobactin biosynthesis, MbtN, in complex
      with its FAD cofactor is presented at 2.30 A resolution. The polypeptide fold of
      MbtN conforms to that of the acyl-CoA dehydrogenase (ACAD) family, consistent
      with its predicted role of introducing a double bond into the acyl chain of
      mycobactin. Structural comparisons and the presence of an acyl carrier protein,
      MbtL, in the same gene locus suggest that MbtN acts on an acyl-(acyl carrier
      protein) rather than an acyl-CoA. A notable feature of the crystal structure is
      the tubular density projecting from N(5) of FAD. This was interpreted as a
      covalently bound polyethylene glycol (PEG) fragment and resides in a hydrophobic
      pocket where the substrate acyl group is likely to bind. The pocket could
      accommodate an acyl chain of 14-21 C atoms, consistent with the expected length
      of the mycobactin acyl chain. Supporting this, steady-state kinetics show that
      MbtN has ACAD activity, preferring acyl chains of at least 16 C atoms. The acyl
      binding pocket adopts a different orientation (relative to the FAD) to other
      structurally characterized ACADs. This difference may be correlated with the
      apparent ability of MbtN to catalyse the formation of an unusual cis double bond
      in the mycobactin acyl chain. 

PMID- 25849398
TI  - Structure of the adenylation-peptidyl carrier protein didomain of the Microcystis
      aeruginosa microcystin synthetase McyG.
AB  - Microcystins, which are the most common cause of hepatotoxicity associated with
      cyanobacterial water blooms, are assembled in vivo on a large multienzyme complex
      via a mixed nonribosomal peptide synthetase/polyketide synthetase (NRPS/PKS). The
      biosynthesis of microcystin in Microcystis aeruginosa PCC 7806 starts with the
      enzyme McyG, which contains an adenylation-peptidyl carrier protein (A-PCP)
      didomain for loading the starter unit to assemble the side chain of an Adda
      residue. However, the catalytic mechanism remains unclear. Here, the 2.45 A
      resolution crystal structure of the McyG A-PCP didomain complexed with the
      catalytic intermediate L-phenylalanyl-adenylate (L-Phe-AMP) is reported. Each
      asymmetric unit contains two protein molecules, one of which consists of the A
      PCP didomain and the other of which comprises only the A domain. Structural
      analyses suggest that Val227 is likely to be critical for the selection of
      hydrophobic substrates. Moreover, two distinct interfaces demonstrating variable
      crosstalk between the PCP domain and the A domain were observed. A catalytic
      cycle for the adenylation and peptide transfer of the A-PCP didomain is proposed.

PMID- 25849399
TI  - The architecture of amyloid-like peptide fibrils revealed by X-ray scattering,
      diffraction and electron microscopy.
AB  - Structural analysis of protein fibrillation is inherently challenging. Given the
      crucial role of fibrils in amyloid diseases, method advancement is urgently
      needed. A hybrid modelling approach is presented enabling detailed analysis of a
      highly ordered and hierarchically organized fibril of the GNNQQNY peptide
      fragment of a yeast prion protein. Data from small-angle X-ray solution
      scattering, fibre diffraction and electron microscopy are combined with existing
      high-resolution X-ray crystallographic structures to investigate the fibrillation
      process and the hierarchical fibril structure of the peptide fragment. The
      elongation of these fibrils proceeds without the accumulation of any detectable
      amount of intermediate oligomeric species, as is otherwise reported for, for
      example, glucagon, insulin and alpha-synuclein. Ribbons constituted of linearly
      arranged protofilaments are formed. An additional hierarchical layer is generated
      via the pairing of ribbons during fibril maturation. Based on the complementary
      data, a quasi-atomic resolution model of the protofilament peptide arrangement is
      suggested. The peptide structure appears in a beta-sheet arrangement reminiscent
      of the beta-zipper structures evident from high-resolution crystal structures,
      with specific differences in the relative peptide orientation. The complexity of
      protein fibrillation and structure emphasizes the need to use multiple
      complementary methods. 

PMID- 25849401
TI  - Structure and catalytic mechanism of the evolutionarily unique bacterial chalcone
      isomerase.
AB  - Flavonoids represent a large class of secondary metabolites produced by plants.
      These polyphenolic compounds are well known for their antioxidative abilities,
      are antimicrobial phytoalexins responsible for flower pigmentation to attract
      pollinators and, in addition to other properties, are also specific bacterial
      regulators governing the expression of Rhizobium genes involved in root
      nodulation (Firmin et al., 1986). The bacterial chalcone isomerase (CHI) from
      Eubacterium ramulus catalyses the first step in a flavanone-degradation pathway
      by ring opening of (2S)-naringenin to form naringenin chalcone. The structural
      biology and enzymology of plant CHIs have been well documented, whereas the
      existence of bacterial CHIs has only recently been elucidated. This first
      determination of the structure of a bacterial CHI provides detailed structural
      insights into the key step of the flavonoid-degradation pathway. The active site
      could be confirmed by co-crystallization with the substrate (2S)-naringenin. The
      stereochemistry of the proposed mechanism of the isomerase reaction was verified
      by specific (1)H/(2)H isotope exchange observed by (1)H NMR experiments and was
      further supported by mutagenesis studies. The active site is shielded by a
      flexible lid, the varying structure of which could be modelled in different
      states of the catalytic cycle using small-angle X-ray scattering data together
      with the crystallographic structures. Comparison of bacterial CHI with the plant
      enzyme from Medicago sativa reveals that they have unrelated folds, suggesting
      that the enzyme activity evolved convergently from different ancestor proteins.
      Despite the lack of any functional relationship, the tertiary structure of the
      bacterial CHI shows similarities to the ferredoxin-like fold of a chlorite
      dismutase and the stress-related protein SP1. 

PMID- 25849400
TI  - Structural and biophysical characterization of an epitope-specific engineered Fab
      fragment and complexation with membrane proteins: implications for co
      crystallization.
AB  - Crystallization chaperones are attracting increasing interest as a route to
      crystal growth and structure elucidation of difficult targets such as membrane
      proteins. While strategies to date have typically employed protein-specific
      chaperones, a peptide-specific chaperone to crystallize multiple cognate peptide
      epitope-containing client proteins is envisioned. This would eliminate the target
      specific chaperone-production step and streamline the co-crystallization process.
      Previously, protein engineering and directed evolution were used to generate a
      single-chain variable (scFv) antibody fragment with affinity for the peptide
      sequence EYMPME (scFv/EE). This report details the conversion of scFv/EE to an
      anti-EE Fab format (Fab/EE) followed by its biophysical characterization. The
      addition of constant chains increased the overall stability and had a negligible
      impact on the antigen affinity. The 2.0 A resolution crystal structure of Fab/EE
      reveals contacts with larger surface areas than those of scFv/EE. Surface plasmon
      resonance, an enzyme-linked immunosorbent assay, and size-exclusion
      chromatography were used to assess Fab/EE binding to EE-tagged soluble and
      membrane test proteins: namely, the beta-barrel outer membrane protein intimin
      and alpha-helical A2a G protein-coupled receptor (A2aR). Molecular-dynamics
      simulation of the intimin constructs with and without Fab/EE provides insight
      into the energetic complexities of the co-crystallization approach. 

PMID- 25849402
TI  - Structures of complexes of type 5 17beta-hydroxysteroid dehydrogenase with
      structurally diverse inhibitors: insights into the conformational changes upon
      inhibitor binding.
AB  - Type 5 17beta-hydroxysteroid dehydrogenase (17beta-HSD5) is an aldo-keto
      reductase expressed in the human prostate which catalyzes the conversion of
      androstenedione to testosterone. Testosterone is converted to 5alpha
      dihydrotestosterone, which is present at high concentrations in patients with
      castration-resistant prostate cancer (CRPC). Inhibition of 17beta-HSD5 is
      therefore considered to be a promising therapy for treating CRPC. In the present
      study, crystal structures of complexes of 17beta-HSD5 with structurally diverse
      inhibitors derived from high-throughput screening were determined. In the
      structures of the complexes, various functional groups, including amide, nitro,
      pyrazole and hydroxyl groups, form hydrogen bonds to the catalytic residues
      His117 and Tyr55. In addition, major conformational changes of 17beta-HSD5 were
      observed following the binding of the structurally diverse inhibitors. These
      results demonstrate interactions between 17beta-HSD5 and inhibitors at the atomic
      level and enable structure-based drug design for anti-CRPC therapy. 

PMID- 25849403
TI  - Capture and X-ray diffraction studies of protein microcrystals in a microfluidic
      trap array.
AB  - X-ray free-electron lasers (XFELs) promise to enable the collection of
      interpretable diffraction data from samples that are refractory to data
      collection at synchrotron sources. At present, however, more efficient sample
      delivery methods that minimize the consumption of microcrystalline material are
      needed to allow the application of XFEL sources to a wide range of challenging
      structural targets of biological importance. Here, a microfluidic chip is
      presented in which microcrystals can be captured at fixed, addressable points in
      a trap array from a small volume (<10 ul) of a pre-existing slurry grown off
      chip. The device can be mounted on a standard goniostat for conducting
      diffraction experiments at room temperature without the need for flash-cooling.
      Proof-of-principle tests with a model system (hen egg-white lysozyme)
      demonstrated the high efficiency of the microfluidic approach for crystal
      harvesting, permitting the collection of sufficient data from only 265 single
      crystal still images to permit determination and refinement of the structure of
      the protein. This work shows that microfluidic capture devices can be readily
      used to facilitate data collection from protein microcrystals grown in
      traditional laboratory formats, enabling analysis when cryopreservation is
      problematic or when only small numbers of crystals are available. Such
      microfluidic capture devices may also be useful for data collection at
      synchrotron sources. 

PMID- 25849405
TI  - Cholesterol oxidase: ultrahigh-resolution crystal structure and multipolar atom
      model-based analysis.
AB  - Examination of protein structure at the subatomic level is required to improve
      the understanding of enzymatic function. For this purpose, X-ray diffraction data
      have been collected at 100 K from cholesterol oxidase crystals using synchrotron
      radiation to an optical resolution of 0.94 A. After refinement using the
      spherical atom model, nonmodelled bonding peaks were detected in the Fourier
      residual electron density on some of the individual bonds. Well defined bond
      density was observed in the peptide plane after averaging maps on the residues
      with the lowest thermal motion. The multipolar electron density of the protein
      cofactor complex was modelled by transfer of the ELMAM2 charge-density database,
      and the topology of the intermolecular interactions between the protein and the
      flavin adenine dinucleotide (FAD) cofactor was subsequently investigated. Taking
      advantage of the high resolution of the structure, the stereochemistry of main
      chain bond lengths and of C=O...H-N hydrogen bonds was analyzed with respect to
      the different secondary-structure elements.

PMID- 25849404
TI  - Time-lapse anomalous X-ray diffraction shows how Fe(2+) substrate ions move
      through ferritin protein nanocages to oxidoreductase sites.
AB  - Ferritin superfamily protein cages reversibly synthesize internal biominerals,
      Fe2O3.H2O. Fe(2+) and O2 (or H2O2) substrates bind at oxidoreductase sites in the
      cage, initiating biomineral synthesis to concentrate iron and prevent potentially
      toxic reactions products from Fe(2+)and O2 or H2O2 chemistry. By freezing
      ferritin crystals of Rana catesbeiana ferritin M (RcMf) at different time
      intervals after exposure to a ferrous salt, a series of high-resolution anomalous
      X-ray diffraction data sets were obtained that led to crystal structures that
      allowed the direct observation of ferrous ions entering, moving along and binding
      at enzyme sites in the protein cages. The ensemble of crystal structures from
      both aerobic and anaerobic conditions provides snapshots of the iron substrate
      bound at different cage locations that vary with time. The observed differential
      occupation of the two iron sites in the enzyme oxidoreductase centre (with Glu23
      and Glu58, and with Glu58, His61 and Glu103 as ligands, respectively) and other
      iron-binding sites (with Glu53, His54, Glu57, Glu136 and Asp140 as ligands)
      reflects the approach of the Fe(2+) substrate and its progression before the
      enzymatic cycle 2Fe(2+) + O2 -> Fe(3+)-O-O-Fe(3+) -> Fe(3+)-O(H)-Fe(3+) and
      turnover. The crystal structures also revealed different Fe(2+) coordination
      compounds bound to the ion channels located at the threefold and fourfold
      symmetry axes of the cage. 

PMID- 25849407
TI  - Structural and functional characterization of TesB from Yersinia pestis reveals a
      unique octameric arrangement of hotdog domains.
AB  - Acyl-CoA thioesterases catalyse the hydrolysis of the thioester bonds present
      within a wide range of acyl-CoA substrates, releasing free CoASH and the
      corresponding fatty-acyl conjugate. The TesB-type thioesterases are members of
      the TE4 thioesterase family, one of 25 thioesterase enzyme families characterized
      to date, and contain two fused hotdog domains in both prokaryote and eukaryote
      homologues. Only two structures have been elucidated within this enzyme family,
      and much of the current understanding of the TesB thioesterases has been based on
      the Escherichia coli structure. Yersinia pestis, a highly virulent bacterium,
      encodes only one TesB-type thioesterase in its genome; here, the structural and
      functional characterization of this enzyme are reported, revealing unique
      elements both within the protomer and quaternary arrangements of the hotdog
      domains which have not been reported previously in any thioesterase family. The
      quaternary structure, confirmed using a range of structural and biophysical
      techniques including crystallography, small-angle X-ray scattering, analytical
      ultracentrifugation and size-exclusion chromatography, exhibits a unique
      octameric arrangement of hotdog domains. Interestingly, the same biological unit
      appears to be present in both TesB structures solved to date, and is likely to be
      a conserved and distinguishing feature of TesB-type thioesterases. Analysis of
      the Y. pestis TesB thioesterase activity revealed a strong preference for
      octanoyl-CoA and this is supported by structural analysis of the active site.
      Overall, the results provide novel insights into the structure of TesB
      thioesterases which are likely to be conserved and distinguishing features of the
      TE4 thioesterase family. 

PMID- 25849406
TI  - Combination of X-ray crystallography, SAXS and DEER to obtain the structure of
      the FnIII-3,4 domains of integrin alpha6beta4.
AB  - Integrin alpha6beta4 is a major component of hemidesmosomes that mediate the
      stable anchorage of epithelial cells to the underlying basement membrane.
      Integrin alpha6beta4 has also been implicated in cell proliferation and migration
      and in carcinoma progression. The third and fourth fibronectin type III domains
      (FnIII-3,4) of integrin beta4 mediate binding to the hemidesmosomal proteins
      BPAG1e and BPAG2, and participate in signalling. Here, it is demonstrated that X
      ray crystallography, small-angle X-ray scattering and double electron-electron
      resonance (DEER) complement each other to solve the structure of the FnIII-3,4
      region. The crystal structures of the individual FnIII-3 and FnIII-4 domains were
      solved and the relative arrangement of the FnIII domains was elucidated by
      combining DEER with site-directed spin labelling. Multiple structures of the
      interdomain linker were modelled by Monte Carlo methods complying with DEER
      constraints, and the final structures were selected against experimental
      scattering data. FnIII-3,4 has a compact and cambered flat structure with an
      evolutionary conserved surface that is likely to correspond to a protein
      interaction site. Finally, this hybrid method is of general application for the
      study of other macromolecules and complexes. 

PMID- 25849408
TI  - The role of monovalent cations in the ATPase reaction of DNA gyrase.
AB  - Four new crystal structures of the ATPase domain of the GyrB subunit of
      Escherichia coli DNA gyrase have been determined. One of these, solved in the
      presence of K(+), is the highest resolution structure reported so far for this
      domain and, in conjunction with the three other structures, reveals new insights
      into the function of this domain. Evidence is provided for the existence of two
      monovalent cation-binding sites: site 1, which preferentially binds a K(+) ion
      that interacts directly with the alpha-phosphate of ATP, and site 2, which
      preferentially binds an Na(+) ion and the functional significance of which is not
      clear. The crystallographic data are corroborated by ATPase data, and the
      structures are compared with those of homologues to investigate the broader
      conservation of these sites. 

PMID- 25849410
TI  - Schistosoma mansoni venom allergen-like protein 4 (SmVAL4) is a novel lipid
      binding SCP/TAPS protein that lacks the prototypical CAP motifs. Corrigendum.

PMID- 25849411
TI  - Food colors: Existing and emerging food safety concerns.
AB  - Food colors are added to different types of commodities to increase their visual
      attractiveness or to compensate for natural color variations. The use of these
      additives is strictly regulated in the European Union, the United States, and
      many other countries worldwide. There is a growing concern about the safety of
      some commonly used legal food colorants and there is a trend to replace the
      synthetic forms with natural products. Additionally, a number of dyes with known
      or suspected genotoxic or carcinogenic properties have been shown to be added
      illegally to foods. Robust monitoring programs based on reliable detection
      methods are required to assure the food is free from harmful colors. The aim of
      this review is to present an up to date status of the various concerns arising
      from use of color additives in food. The most important food safety concerns in
      the field of food colors are lack of uniform regulation concerning legal food
      colors worldwide, possible link of artificial colors to hyperactive behavior,
      replacement of synthetic colors with natural ones, and the presence of harmful
      illegal dyes-both known but also new, emerging ones in food. The legal status of
      food color additives in the EU, United States, and worldwide is summarized. The
      reported negative health effects of both legal and illegal colors are presented.
      The European Rapid Alert System for Food and Feed notifications and US import
      alerts concerning food colors are analyzed and trends in fraudulent use of color
      additives identified. The detection methods for synthetic colors are also
      reviewed.

PMID- 25849409
TI  - Structures of the hydrolase domain of zebrafish 10-formyltetrahydrofolate
      dehydrogenase and its complexes reveal a complete set of key residues for
      hydrolysis and product inhibition.
AB  - 10-Formyltetrahydrofolate dehydrogenase (FDH), which is composed of a small N
      terminal domain (Nt-FDH) and a large C-terminal domain, is an abundant folate
      enzyme in the liver and converts 10-formyltetrahydrofolate (10-FTHF) to
      tetrahydrofolate (THF) and CO2. Nt-FDH alone possesses a hydrolase activity,
      which converts 10-FTHF to THF and formate in the presence of beta
      mercaptoethanol. To elucidate the catalytic mechanism of Nt-FDH, crystal
      structures of apo-form zNt-FDH from zebrafish and its complexes with the
      substrate analogue 10-formyl-5,8-dideazafolate (10-FDDF) and with the products
      THF and formate have been determined. The structures reveal that the
      conformations of three loops (residues 86-90, 135-143 and 200-203) are altered
      upon ligand (10-FDDF or THF) binding in the active site. The orientations and
      geometries of key residues, including Phe89, His106, Arg114, Asp142 and Tyr200,
      are adjusted for substrate binding and product release during catalysis. Among
      them, Tyr200 is especially crucial for product release. An additional potential
      THF binding site is identified in the cavity between two zNt-FDH molecules, which
      might contribute to the properties of product inhibition and THF storage reported
      for FDH. Together with mutagenesis studies and activity assays, the structures of
      zNt-FDH and its complexes provide a coherent picture of the active site and a
      potential THF binding site of zNt-FDH along with the substrate and product
      specificity, lending new insights into the molecular mechanism underlying the
      enzymatic properties of Nt-FDH. 

PMID- 25849413
TI  - Laboratory- and Field-Based Assessment of Maximal Aerobic Power of Elite Stand-Up
      Paddle-Board Athletes.
AB  - PURPOSE: Stand-up paddle boarding (SUP) is a rapidly growing sport and
      recreational activity for which only anecdotal evidence exists on its proposed
      health, fitness, and injury-rehabilitation benefits. PARTICIPANTS: 10
      internationally and nationally ranked elite SUP athletes. METHODS: Participants
      were assessed for their maximal aerobic power on an ergometer in a laboratory and
      compared with other water-based athletes. Field-based assessments were
      subsequently performed using a portable gas-analysis system, and a correlation
      between the 2 measures was performed. RESULTS: Maximal aerobic power (relative)
      was significantly higher (P = .037) when measured in the field with a portable
      gas-analysis system (45.48 +/- 6.96 mL . kg(-1) . min(-1)) than with laboratory
      based metabolic-cart measurements (43.20 +/- 6.67 mL . kg(-1) . min(-1)). There
      was a strong, positive correlation (r = .907) between laboratory and field
      maximal aerobic power results. Significantly higher (P = .000) measures of SUP
      paddling speed were found in the field than with the laboratory ergometer
      (+42.39%). There were no significant differences in maximal heart rate between
      the laboratory and field settings (P = .576). CONCLUSION: The results demonstrate
      the maximal aerobic power representative of internationally and nationally ranked
      SUP athletes and show that SUP athletes can be assessed for maximal aerobic power
      in the laboratory with high correlation to field-based measures. The field-based
      portable gas-analysis unit has a tendency to consistently measure higher oxygen
      consumption. Elite SUP athletes display aerobic power outputs similar to those of
      other upper-limb-dominant elite water-based athletes (surfing, dragon-boat
      racing, and canoeing).

PMID- 25849412
TI  - The role of polymerase chain reaction of high-risk human papilloma virus in the
      screening of high-grade squamous intraepithelial lesions in the anal mucosa of
      human immunodeficiency virus-positive males having sex with males.
AB  - OBJECTIVES: To evaluate the advantages of cytology and PCR of high-risk human
      papilloma virus (PCR HR-HPV) infection in biopsy-derived diagnosis of high-grade
      squamous intraepithelial lesions (HSIL = AIN2/AIN3) in HIV-positive men having
      sex with men (MSM). METHODS: This is a single-centered study conducted between
      May 2010 and May 2014 in patients (n = 201, mean age 37 years) recruited from our
      outpatient clinic. Samples of anal canal mucosa were taken into liquid medium for
      PCR HPV analysis and for cytology. Anoscopy was performed for histology
      evaluation. RESULTS: Anoscopy showed 33.8% were normal, 47.8% low-grade squamous
      intraepithelial lesions (LSIL), and 18.4% HSIL; 80.2% had HR-HPV. PCR of HR-HPV
      had greater sensitivity than did cytology (88.8% vs. 75.7%) in HSIL screening,
      with similar positive (PPV) and negative predictive value (NPV) of 20.3 vs. 22.9
      and 89.7 vs. 88.1, respectively. Combining both tests increased the sensitivity
      and NPV of HSIL diagnosis to 100%. Correlation of cytology vs. histology was,
      generally, very low and PCR of HR-HPV vs. histology was non-existent (<0.2) or
      low (<0.4). Area under the receiver operating characteristics (AUROC) curve
      analysis of cytology and PCR HR-HPV for the diagnosis of HSIL was poor (<0.6).
      Multivariate regression analysis showed protective factors against HSIL were:
      viral suppression (OR: 0.312; 95%CI: 0.099-0.984), and/or syphilis infection (OR:
      0.193; 95%CI: 0.045-0.827). HSIL risk was associated with HPV-68 genotype (OR:
      20.1; 95%CI: 2.04-197.82). CONCLUSIONS: When cytology and PCR HR-HPV findings are
      normal, the diagnosis of pre-malignant HSIL can be reliably ruled-out in HIV
      suppression with treatment protects against the appearance of HSIL [corrected].

PMID- 25849414
TI  - Palladium(II)-catalyzed intramolecular carboxypalladation-olefin insertion
      cascade: direct access to indeno[1,2-b]furan-2-ones.
AB  - A catalytic, atom-economical, domino 5-endo-dig cyclization-intramolecular olefin
      insertion sequence was developed under mild conditions. Aryl alkynoic acids
      bearing a tethered enone partner afforded the indeno[1,2-b]furan-2-ones, the core
      skeleton present in a number of biologically significant molecules including the
      natural product solanacol, under ligand-free, palladium-catalyzed reaction
      conditions in high yields. The competitive beta-hydride elimination in the final
      step leading to the conjugated analogs was avoided by the addition of lithium
      bromide. A plausible mechanism for this domino sequence is proposed involving
      intramolecular carboxypalladation and olefin insertion steps. 

PMID- 25849415
TI  - The effects of static stretching on speed and agility: One or multiple repetition
      protocols?
AB  - Although static stretching (SS) is utilized during warm-up before training and
      competition, the results about its effects on performance remain controversial.
      We examined whether performing a stretch of short-to-moderate duration (<60 sec)
      in a single repetition produces a similar or different effect on speed and
      agility performance from the effect which is produced while performing the same
      stretch in multiple repetitions of the same total duration. According to a
      repeated measurement design, 40 trained males were randomly assigned to either
      (1) a single repetition group or (2) a multiple repetition group. The
      participants in each group performed five trials: a control trial (no stretches
      were performed) and four experimental trials of SS protocols consisting of five
      exercises performed at either 20 sec (2 * 10 in the second group), 30 sec (3 * 10
      in the second group), 40 sec (4 * 10 in the second group) or 60 sec (6 * 10 in
      the second group) of total duration. A two-way repeated measures analysis of
      variance showed that the participants in both group improved their speed
      performance in response to the 20-sec trial, whereas agility remained unaffected.
      Data analysis also revealed that the repetition number did not affect speed and
      agility performance. These data suggest that SS of short duration (<30 sec) may
      actually improve acute speed performance, whereas SS of moderate duration may not
      hamper speed and agility performance. Moreover, the effects of SS protocols are
      related to the total duration of each exercise and not to the number of
      repetitions in which each exercise is performed. 

PMID- 25849417
TI  - Unconventional actins and actin-binding proteins in human protozoan parasites.
AB  - Actin and its regulatory proteins play a key role in several essential cellular
      processes such as cell movement, intracellular trafficking and cytokinesis in
      most eukaryotes. While these proteins are highly conserved in higher eukaryotes,
      a number of unicellular eukaryotic organisms contain divergent forms of these
      proteins which have highly unusual biochemical and structural properties. Here,
      we review the biochemical and structural properties of these unconventional
      actins and their core binding proteins which are present in commonly occurring
      human protozoan parasites. 

PMID- 25849416
TI  - Burden of invasive group B Streptococcus disease and early neurological sequelae
      in South African infants.
AB  - INTRODUCTION: Group B Streptococcus (GBS) is a leading cause of neonatal sepsis
      and meningitis. We aimed to evaluate the burden of invasive early-onset (0-6 days
      of life, EOD) and late-onset (7-89 days, LOD) GBS disease and subsequent
      neurological sequelae in infants from a setting with a high prevalence (29.5%) of
      HIV among pregnant women. METHODS: A case-control study was undertaken at three
      secondary-tertiary care public hospitals in Johannesburg. Invasive cases in
      infants <3 months age were identified by surveillance of laboratories from
      November 2012 to February 2014. Neurodevelopmental screening was done in
      surviving cases and controls at 3 and 6 months of age. RESULTS: We identified 122
      cases of invasive GBS disease over a 12 month period. Although the incidence (per
      1,000 live births) of EOD was similar between HIV-exposed and HIV-unexposed
      infants (1.13 vs. 1.46; p = 0.487), there was a 4.67-fold (95%CI: 2.24-9.74)
      greater risk for LOD in HIV-exposed infants (2.27 vs. 0.49; p<0.001). Overall,
      serotypes Ia, Ib and III constituted 75.8% and 92.5% of EOD and LOD,
      respectively. Risk factors for EOD included offensive draining liquor (adjusted
      Odds Ratio: 27.37; 95%CI: 1.94-386.50) and maternal GBS bacteriuria (aOR: 8.41;
      95%CI: 1.44-49.15), which was also a risk-factor for LOD (aOR: 3.49; 95%CI: 1.17
      10.40). The overall case fatality rate among cases was 18.0%. The adjusted odds
      for neurological sequelae at 6 months age was 13.18-fold (95%CI: 1.44-120.95)
      greater in cases (13.2%) than controls (0.4%). DISCUSSION: The high burden of
      invasive GBS disease in South Africa, which is also associated with high case
      fatality rates and significant neurological sequelae among survivors, is partly
      due to the heightened risk for LOD in infants born to HIV-infected women. An
      effective trivalent GBS conjugate vaccine targeted at pregnant women could
      prevent invasive GBS disease in this setting.

PMID- 25849418
TI  - Mitochondrial carnitine/acylcarnitine transporter, a novel target of mercury
      toxicity.
AB  - The effect of Hg(2+) and CH3Hg(+) on the mitochondrial carnitine/acylcarnitine
      transporter (CACT) has been studied on the recombinant protein and on the CACT
      extracted from HeLa cells or Zebrafish and reconstituted in proteoliposomes.
      Transport was abolished upon treatment of the recombinant CACT in proteoliposomes
      by Hg(2+) or CH3Hg(+). Inhibition was reversed by the SH reducing agent 1,4
      dithioerythritol, GSH, and N-acetylcysteine. IC50 for Hg(2+) and CH3Hg(+) of 90
      nM and 137 nM, respectively, were measured by dose-response analyses. Inhibition
      was abolished in the C-less CACT mutant. Strong reduction of inhibition by both
      reagents was observed in the C136A and some reduction in the C155A mutants.
      Inhibition similar to that of the WT was observed in the
      C23V/C58V/C89S/C155V/C283S mutant, containing only C136. Optimal inhibition by
      Hg(2+)was found in the four replacement mutants C23V/C58V/C89S/C283S containing
      both C136 and C155 indicating cross-reaction of Hg(2+) with the two Cys residues.
      Inhibition kinetic analysis showed mixed inhibition by Hg(2+) or competitive
      inhibition by CH3Hg(+). HeLa cells or Zebrafish were treated with the more potent
      inhibitor. Ten micromolar HgCl2 caused clear impairment of viability of HeLa
      cells. The transport assay in proteoliposomes with CACT extracted from treated
      cells showed that the transporter was inactivated and that DTE rescued the
      activity. Nearly identical results were observed with Zebrafish upon extraction
      of the CACT from the liver of the treated animals that, indeed, showed
      accumulation of the mercurial compound. 

PMID- 25849419
TI  - From the impact factor to DORA and the scientific content of articles.

PMID- 25849422
TI  - In vivo secretion of anti-CD3 * anti-tumor bispecific antibodies by gene-modified
      cells: over a decade of T-cell engagement.

PMID- 25849423
TI  - Transduction of antigen-presenting cells in the brain by AAV9 warrants caution in
      preclinical studies.

PMID- 25849424
TI  - Response to "in vivo secretion of anti-CD3 * anti-tumor bispecific antibodies by
      gene-modified cells: over a decade of T-cell engagement".

PMID- 25849425
TI  - A shot in the bone corrects a genetic disease.

PMID- 25849427
TI  - Corrigendum to "CD133-targeted gene transfer into long-term repopulating
      hematopoietic stem cells".

PMID- 25849426
TI  - Antiobesity strategy targets energy economy safeguards.

PMID- 25849428
TI  - Corrigendum to "let-7 microRNAs regenerate peripheral nerve regeneration by
      targeting nerve growth factor".

PMID- 25849429
TI  - Reconstructible phylogenetic networks: do not distinguish the indistinguishable.
AB  - Phylogenetic networks represent the evolution of organisms that have undergone
      reticulate events, such as recombination, hybrid speciation or lateral gene
      transfer. An important way to interpret a phylogenetic network is in terms of the
      trees it displays, which represent all the possible histories of the characters
      carried by the organisms in the network. Interestingly, however, different
      networks may display exactly the same set of trees, an observation that poses a
      problem for network reconstruction: from the perspective of many inference
      methods such networks are "indistinguishable". This is true for all methods that
      evaluate a phylogenetic network solely on the basis of how well the displayed
      trees fit the available data, including all methods based on input data
      consisting of clades, triples, quartets, or trees with any number of taxa, and
      also sequence-based approaches such as popular formalisations of maximum
      parsimony and maximum likelihood for networks. This identifiability problem is
      partially solved by accounting for branch lengths, although this merely reduces
      the frequency of the problem. Here we propose that network inference methods
      should only attempt to reconstruct what they can uniquely identify. To this end,
      we introduce a novel definition of what constitutes a uniquely reconstructible
      network. For any given set of indistinguishable networks, we define a canonical
      network that, under mild assumptions, is unique and thus representative of the
      entire set. Given data that underwent reticulate evolution, only the canonical
      form of the underlying phylogenetic network can be uniquely reconstructed. While
      on the methodological side this will imply a drastic reduction of the solution
      space in network inference, for the study of reticulate evolution this is a
      fundamental limitation that will require an important change of perspective when
      interpreting phylogenetic networks. 

PMID- 25849431
TI  - Correction: genetic dissection of photoperiod response based on GWAS of pre
      anthesis phase duration in spring barley.

PMID- 25849430
TI  - Suppression of Escherichia coli O157:H7 by Dung Beetles (Coleoptera:
      Scarabaeidae) using the lowbush blueberry agroecosystem as a model system.
AB  - Wildlife as a source of microbial contamination is a food safety concern. Deer
      feces (scat) have been determined as a point source for Escherichia coli O157:H7
      contamination of fresh produce. The ecological role of the scooped scarab
      (Onthophagus hecate (Panzer)), a generalist dung beetle species common in Maine
      blueberry fields, was explored as a biological control agent and alternatively as
      a pathogen vector between deer scat and food. A large-scale field survey of
      wildlife scat indicated that pathogenic E. coli O157:H7 was present, albeit at a
      low prevalence (1.9% of samples, n = 318), in the Maine lowbush blueberry
      agroecosystem. A manipulative field experiment verified that, should contact
      occur between deer scat and blueberry plants and fruit during the summer,
      contamination with E. coli O157:H7 can occur and persist for more than 72 h. For
      both the positive control and an experimental scat inoculation treatment, the
      levels of the bacterial population decreased over time, but at different rates
      (treatment x time interaction: F (1.9,18.8) = 358.486, P < 0.0001). The positive
      control inoculation, which resulted in a higher initial E. coli level on fruit,
      decayed at a faster rate than inoculation of fruit via scat in the experimental
      treatment. We conducted 2 laboratory studies to elucidate aspects of dung beetle
      feeding ecology as it relates to suppression of E. coli O157:H7 from deer scat to
      lowbush blueberry fruit. In both experiments, dung beetles buried the same amount
      of scat whether or not the scat was inoculated with the pathogen (F(1,6) = 0.001;
      P = 0.999 and (F (2,17) = 4.10, P = 0.147). Beetles feeding on E. coli inoculated
      deer scat were not found to vector the pathogen to fruit. In two studies, beetles
      lowered the amount of pathogenic E. coli persisting in soils compared to soils
      without beetles (F (2,9) = 7.757; P = 0.05 and F (2,17) = 8.0621, P = 0.004). Our
      study suggests that the dung beetle species, Onthophagus hecate, has the
      potential to contribute to the suppression of E. coli O157:H7 in agricultural
      landscapes. 

PMID- 25849432
TI  - Propofol post-conditioning protects the blood brain barrier by decreasing matrix
      metalloproteinase-9 and aquaporin-4 expression and improves the neurobehavioral
      outcome in a rat model of focal cerebral ischemia-reperfusion injury.
AB  - Propofol, an intravenous anesthetic, inhibits neuronal apoptosis induced by
      ischemic stroke, protects the brain from ischemia/reperfusion injury and improves
      neuronal function. However, whether propofol is able to protect the blood brain
      barrier (BBB) and the underlying mechanisms have remained to be elucidated. In
      the present study, a rat model of cerebral ischemia/reperfusion was established,
      using a thread embolism to achieve middle cerebral artery occlusion. Rats were
      treated with propofol (propofol post-conditioning) or physiological saline
      (control) administered by intravenous injection 30 min following reperfusion.
      Twenty-four hours following reperfusion, neurobehavioral manifestations were
      assessed. The levels of cephaloedema, damage to the BBB and expression levels of
      matrix metalloproteinase-9 (MMP-9), aquaporin-4 (AQP-4) and phosphorylated c-Jun
      N-terminal kinase (pJNK) were determined in order to evaluate the effects of
      propofol on the BBB. In comparison to the cerebral ischemia/reperfusion group,
      the levels of brain water content and Evans blue content, as well as the
      expression levels of MMP-9, AQP-4 and pJNK were significantly reduced in the
      propofol post-conditioning group. These results indicated that propofol post
      conditioning improved the neurobehavioral manifestations and attenuated the BBB
      damage and cephaloedema induced following cerebral ischemia/reperfusion. This
      effect may be due to the inhibition of MMP-9 and AQP-4 expression, and the
      concurrent decrease in JNK phosphorylation.

PMID- 25849433
TI  - Improving men's participation in preventing mother-to-child transmission of HIV
      as a maternal, neonatal, and child health priority in South Africa.

PMID- 25849434
TI  - Women in "Sexual" Pain: Exploring the Manifestations of Vulvodynia.
AB  - This study explored the sexual and pain histories and pain presentations of women
      with forms of chronic vulvar pain (i.e., vulvodynia). One hundred and seventy
      seven women with five subtypes of vulvodynia completed an online questionnaire.
      Groups were similar across several domains: participants experienced pain for
      many years during sexual and nonsexual activities, and pain was rated as moderate
      to severe. However, several differences emerged when considering pain
      development, number of sexual partners, and treatment seeking. This study
      illustrates how severe vulvodynia pain can be, regardless of subtype. However,
      not all vulvodynia sufferers are alike, and distinctions between research and
      clinical practice are highlighted. 

PMID- 25849436
TI  - TGF-beta1 induced transdifferentiation of rpe cells is mediated by TAK1.
AB  - BACKGROUND AND AIM: Proliferative vitreoretinopathy (PVR) is an active process
      that develops as a complication upon retinal detachment (RD), accompanied by
      formation of fibrotic tissue. The main cells involved in the development of
      fibrotic tissue during PVR are the retinal pigment epithelial (RPE) cells. The
      RPE cells undergo epithelial-mesenchymal transition (EMT) which leads to complex
      retinal detachment and loss of vision. Transforming growth factor-beta1 (TGF
      beta1) is considered as the main player in the EMT of RPE cells, even though the
      mechanism is not fully understood. This study was performed to determine the
      possible involvement of transforming growth factor beta activated kinase 1 (TAK1)
      in the EMT process of the RPE cells. METHODOLOGY: ARPE-19 Cells were treated with
      5Z-7 oxozeaenol (TAK1 inhibitor) or SB431542 (TGF-beta1 receptor kinase
      inhibitor) followed by TGF-beta1 stimulation. Immunofluorescence, scratch assay
      Real time PCR and collagen contraction assay assessed the EMT features. The
      phosphorylation of Smad2/3 and p38 was examined using western blots analysis.
      RESULTS: This study demonstrates that stimulation of RPE cells with TGF-beta1
      increases alpha-SMA expression, cell migration and cell contractility, all of
      which are EMT features. Remarkably, addition of TAK1 inhibitor abolishes all
      these processes. Furthermore, we show hereby that TAK1 regulates not only the
      activation of the non-canonical cascade of TGF-beta1 (p38), but also the
      canonical cascade, the Smad2/3 activation. Thus, the outcome of the TGF-beta
      response in RPE cells is TAK1 dependent. CONCLUSIONS/SIGNIFICANCE: This work
      demonstrated TAK1, a component of the non-canonical pathway of TGF-beta1, is a
      key player in the EMT process, thus provides deep insight into the pathogenesis
      of PVR. The ability to halt the process of EMT in RPE cells may reduce the
      severity of the fibrotic response that occurs upon PVR, leading to a better
      prognosis and increase the probability of success in RD treatment.

PMID- 25849437
TI  - Comprehensive analysis of maillard protein modifications in human lenses: effect
      of age and cataract.
AB  - In human lens proteins, advanced glycation endproducts (AGEs) originate from the
      reaction of glycating agents, e.g., vitamin C and glucose. AGEs have been
      considered to play a significant role in lens aging and cataract formation.
      Although several AGEs have been detected in the human lens, the contribution of
      individual glycating agents to their formation remains unclear. A highly
      sensitive liquid chromatography-tandem mass spectrometry multimethod was
      developed that allowed us to quantitate 21 protein modifications in normal and
      cataractous lenses, respectively. N(6)-Carboxymethyl lysine, N(6)-carboxyethyl
      lysine, N(7)-carboxyethyl arginine, methylglyoxal hydroimidazolone 1, and N(6)
      lactoyl lysine were found to be the major Maillard protein modifications among
      these AGEs. The novel vitamin C specific amide AGEs, N(6)-xylonyl and N(6)
      lyxonyl lysine, but also AGEs from glyoxal were detected, albeit in minor
      quantities. Among the 21 modifications, AGEs from the Amadori product (derived
      from the reaction of glucose and lysine) and methylglyoxal were dominant.

PMID- 25849438
TI  - Drug therapy for patients with systolic heart failure after the PARADIGM-HF
      trial: in need of a new paradigm of LCZ696 implementation in clinical practice.
AB  - Heart failure represents a primary cause of morbidity and mortality in older
      people and despite significant therapeutic advances, it is still characterized by
      important unmet needs, thus remaining a challenging field of clinical research.
      The recent PARADIGM-HF trial compared the novel compound LCZ696, a combination of
      the angiotensin receptor blocker valsartan and the neprilysin inhibitor
      sacubitril, versus the angiotensin-converting enzyme inhibitor enalapril in 8,442
      patients with symptomatic chronic systolic heart failure. LCZ696 led to a 20%
      reduction in the rate of death or hospitalization for heart failure and a 16%
      reduction in the rate of all-cause death compared to enalapril at 3.5 years of
      follow-up. Despite those impressive results, the clinical application of this
      novel agent that requires the substitution of a cornerstone of current heart
      failure therapy, the angiotensin-converting enzyme inhibitors, should follow
      careful steps as imposed by the study design, the recruited population and the
      outcome in specific patient subgroups. Further insights into the effects of
      LCZ696 will be provided by the ongoing PARAGON-HF trial in patients with
      diastolic heart failure. 

PMID- 25849439
TI  - Regulation of Apoptotic Endonucleases by EndoG.
AB  - Cells contain several apoptotic endonucleases, which appear to act simultaneously
      before and after cell death by destroying the host cell DNA. It is largely
      unknown how the endonucleases are being induced and whether they can regulate
      each other. This study was performed to determine whether apoptotic mitochondrial
      endonuclease G (EndoG) can regulate expression of other apoptotic endonucleases.
      The study showed that overexpression of mature EndoG in kidney tubular epithelial
      NRK-52E cells can increase expression of caspase-activated DNase (CAD) and four
      endonucleases that belong to DNase I group including DNase I, DNase X, DNase IL2,
      and DNase gamma, but not endonucleases of the DNase 2 group. The induction of
      DNase I-type endonucleases was associated with DNA degradation in promoter/exon 1
      regions of the endonuclease genes. These results together with findings on
      colocalization of immunostained endonucleases and TUNEL suggest that DNA
      fragmentation after EndoG overexpression was caused by DNase I endonucleases and
      CAD in addition to EndoG itself. Overall, these data provide first evidence for
      the existence of the integral network of apoptotic endonucleases regulated by
      EndoG.

PMID- 25849440
TI  - Incidence and risk factors for neonatal tetanus in admissions to Kilifi County
      Hospital, Kenya.
AB  - BACKGROUND: Neonatal Tetanus (NT) is a preventable cause of mortality and
      neurological sequelae that occurs at higher incidence in resource-poor countries,
      presumably because of low maternal immunisation rates and unhygienic cord care
      practices. We aimed to determine changes in the incidence of NT, characterize and
      investigate the associated risk factors and mortality in a prospective cohort
      study including all admissions over a 15-year period at a County hospital on the
      Kenyan coast, a region with relatively high historical NT rates within Kenya.
      METHODS: We assessed all neonatal admissions to Kilifi County Hospital in Kenya
      (1999-2013) and identified cases of NT (standard clinical case definition)
      admitted during this time. Poisson regression was used to examine change in
      incidence of NT using accurate denominator data from an area of active
      demographic surveillance. Logistic regression was used to investigate the risk
      factors for NT and factors associated with mortality in NT amongst neonatal
      admissions. A subset of sera from mothers (n = 61) and neonates (n = 47) were
      tested for anti-tetanus antibodies. RESULTS: There were 191 NT admissions, of
      whom 187 (98%) were home deliveries. Incidence of NT declined significantly
      (Incidence Rate Ratio: 0.85 (95% Confidence interval 0.81-0.89), P<0.001) but the
      case fatality (62%) did not change over the study period (P = 0.536). Younger
      infant age at admission (P = 0.001) was the only independent predictor of
      mortality. Compared to neonatal hospital admittee controls, the proportion of
      home births was higher among the cases. Sera tested for antitetanus antibodies
      showed most mothers (50/61, 82%) had undetectable levels of antitetanus
      antibodies, and most (8/9, 89%) mothers with detectable antibodies had a neonate
      without protective levels. CONCLUSIONS: Incidence of NT in Kilifi County has
      significantly reduced, with reductions following immunisation campaigns. Our
      results suggest immunisation efforts are effective if sustained and efforts
      should continue to expand coverage.

PMID- 25849441
TI  - The application of multiplex fluorimetric sensor for the analysis of flavonoids
      content in the medicinal herbs family Asteraceae, Lamiaceae, Rosaceae.
AB  - BACKGROUND: The aim of our research work was to quantify total flavonoid contents
      in the leaves of 13 plant species family Asteraceae, 8 representatives of family
      Lamiaceae and 9 plant species belonging to family Rosaceae, using the multiplex
      fluorimetric sensor. Fluorescence was measured using optical fluorescence
      apparatus Multiplex(R) 3 (Force-A, France) for non-destructive flavonoids
      estimation. The content of total flavonoids was estimated by FLAV index
      (expressed in relative units), that is deduced from flavonoids UV absorbing
      properties. RESULTS: Among observed plant species, the highest amount of total
      flavonoids has been found in leaves of Helianthus multiflorus (1.65 RU) and
      Echinops ritro (1.27 RU), Rudbeckia fulgida (1.13 RU) belonging to the family
      Asteraceae. Lowest flavonoid content has been observed in the leaves of marigold
      (Calendula officinalis) (0.14 RU) also belonging to family Asteraceae. The
      highest content of flavonoids among experimental plants of family Rosaceae has
      been estimated in the leaves of Rosa canina (1.18 RU) and among plant species of
      family Lamiaceae in the leaves of Coleus blumei (0.90 RU). CONCLUSIONS: This
      research work was done as pre-screening of flavonoids content in the leaves of
      plant species belonging to family Asteraceae, Lamiaceae and Rosaceae. Results
      indicated that statistically significant differences (P > 0.05) in flavonoids
      content were observed not only between families, but also among individual plant
      species within one family.

PMID- 25849442
TI  - A versatile technology for droplet-based microfluidics: thermomechanical
      actuation.
AB  - We report on a versatile technique for microfluidic droplet manipulation that
      proves effective at every step: from droplet generation to propulsion to sorting,
      rearrangement or break-up. Non-wetting droplets are thermomechanically actuated
      in a microfluidic chip using local heating resistors. Controlled temperature
      variation induces local dilation of the PDMS wall above the resistor, which
      drives the droplet away from the hot (i.e. constricted) region (B. Selva, I.
      Cantat and M.-C. Jullien, Phys. Fluids, 2011, 23, 052002). Adapted placing and
      actuation of such resistors thus allow us to push forward, stop, store and
      release, or even break up droplets, at the price of low electric power
      consumption (<150 mW). We believe this technically accessible method to provide a
      useful tool for droplet microfluidics. 

PMID- 25849444
TI  - Regioselectivity in the Au-catalyzed hydration and hydroalkoxylation of alkynes.
AB  - Over the past decade and a half, homogenous gold catalysis has emerged as a
      diverse and rich field of research resulting in the continuous development of new
      methods for organic synthesis. The activation of alkynes towards nucleophilic
      attack by Au(I) and Au(III) complexes is a well-established mode of reactivity
      and the gold-catalyzed hydration and hydroalkoxylation of alkynes are two of the
      more well-explored reaction pathways. Although these classes of reactions have
      seen continuous development since their initial reports, achieving
      regioselectivity persists as one of the most challenging issues for this
      chemistry. This article aims to draw attention to the general problem of
      regioselectivity in these reactions. A select set of examples is presented to
      highlight the challenges and survey some of the strategies employed to address
      this problem. 

PMID- 25849445
TI  - Mechanism of rhodium-catalyzed cyclopropanation/cyclization of allenynes.
AB  - The rhodium-catalyzed cyclopropanation/cyclization of allenynes was investigated
      by means of DFT calculations. The results show that the cyclopropanation via the
      proposed stepwise C(sp(3))-H activation (sigma-bond metathesis/C-H reductive
      elimination) was kinetically unfavorable. Instead, a concerted C(sp(3))-H
      activation pathway, namely the metal-assisted sigma-bond metathesis, in which the
      hydrogen was directly transferred to the rhodacyclopentane assisted by the Rh
      center followed by a C-C reductive elimination, was found to explain the
      experimental results. 

PMID- 25849443
TI  - The nuclear receptors of Biomphalaria glabrata and Lottia gigantea: implications
      for developing new model organisms.
AB  - Nuclear receptors (NRs) are transcription regulators involved in an array of
      diverse physiological functions including key roles in endocrine and metabolic
      function. The aim of this study was to identify nuclear receptors in the fully
      sequenced genome of the gastropod snail, Biomphalaria glabrata, intermediate host
      for Schistosoma mansoni and compare these to known vertebrate NRs, with a view to
      assessing the snail's potential as a invertebrate model organism for endocrine
      function, both as a prospective new test organism and to elucidate the
      fundamental genetic and mechanistic causes of disease. For comparative purposes,
      the genome of a second gastropod, the owl limpet, Lottia gigantea was also
      investigated for nuclear receptors. Thirty-nine and thirty-three putative NRs
      were identified from the B. glabrata and L. gigantea genomes respectively, based
      on the presence of a conserved DNA-binding domain and/or ligand-binding domain.
      Nuclear receptor transcript expression was confirmed and sequences were subjected
      to a comparative phylogenetic analysis, which demonstrated that these molluscs
      have representatives of all the major NR subfamilies (1-6). Many of the
      identified NRs are conserved between vertebrates and invertebrates, however
      differences exist, most notably, the absence of receptors of Group 3C, which
      includes some of the vertebrate endocrine hormone targets. The mollusc genomes
      also contain NR homologues that are present in insects and nematodes but not in
      vertebrates, such as Group 1J (HR48/DAF12/HR96). The identification of many
      shared receptors between humans and molluscs indicates the potential for molluscs
      as model organisms; however the absence of several steroid hormone receptors
      indicates snail endocrine systems are fundamentally different. 

PMID- 25849446
TI  - Correction: one-step multiplex PCR assay for detecting Streptococcus pneumoniae
      serogroups/types covered by 13-valent pneumococcal conjugate vaccine (PCV13).

PMID- 25849447
TI  - Correction to Imidazol-1-ylethylindazole Voltage-Gated Sodium Channel Ligands Are
      Neuroprotective during Optic Neuritis in a Mouse Model of Multiple Sclerosis.

PMID- 25849448
TI  - Breast cancer or metastasis? An unusual case of metastatic malignant pleural
      mesothelioma to the breast.
AB  - BACKGROUND: Metastases to the breast from extramammary malignancies are very
      rare, and ruling out the diagnosis of primary breast tumor is important in order
      to decide on clinical management and predict prognosis. CASE PRESENTATION:
      Clinical examination revealed in a 49-year-old hairdresser a 3-cm hard lump
      adherent to the underlying layers in the right breast. Trucut biopsy was
      performed. Histology showed a solid proliferation of medium-sized neoplastic
      polygonal cells. Immunohistochemical analysis showed tumor cells diffusely
      positive for cytokeratin 8/18 and calretinin and focally positive for cytokeratin
      5/6 and Wilms' tumor 1, e-cadherin, and human bone marrow endothelial-1. Estrogen
      receptors and progesterone receptors were negative. The final diagnosis was
      metastatic epithelioid malignant pleural mesothelioma. CONCLUSIONS:
      Immunohistochemistry is an important tool for a conclusive diagnosis of malignant
      pleural mesothelioma. Owing to the degree of histological and immunohistochemical
      overlap, a high level of clinical suspicion is essential in order to avoid
      unnecessary mutilating surgery.

PMID- 25849449
TI  - Threshold Photoelectron Spectra of Combustion Relevant C4H5 and C4H7 Isomers.
AB  - Threshold photoelectron spectra of combustion relevant C4H5 isomers, 2-butyn-1-yl
      and 1-butyn-3-yl, and C4H7 isomers, 1-methylallyl and 2-methylallyl, have been
      recorded using vacuum ultraviolet synchrotron radiation. Adiabatic ionization
      energies (IEad) have been determined by assigning spectroscopic transitions in
      mass-selected threshold photoelectron spectra aided by Franck-Condon simulations.
      The following values were obtained: (7.97 +/- 0.02) eV (1-butyn-3-yl), (7.94 +/-
      0.02) eV (2-butyn-1-yl), (7.48 +/- 0.01) eV (1-E-methylallyl), (7.59 +/- 0.01) eV
      (1-Z-methylallyl), and (7.88 +/- 0.01) eV (2-methylallyl). Good agreement with
      CBS-QB3 calculations and simulations could be achieved. 

PMID- 25849451
TI  - Effectiveness of a pilot partner notification program for new HIV cases in
      Barcelona, Spain.
AB  - BACKGROUND: An estimated 30% of HIV cases in the European Union are not aware of
      their serological status. This study aimed to assess the effectiveness of a pilot
      HIV partner notification program. METHODS: HIV cases diagnosed between January
      2012 and June 2013 at two healthcare settings in Barcelona were invited to
      participate in a prospective survey. We identified process and outcome measures
      to evaluate this partner notification program, including the number of partners
      identified per interviewed index case, the proportion of partners tested for HIV
      as a result of the partner notification, and the proportion of new HIV diagnoses
      among their sex or needle-sharing partners. RESULTS: Of the 125 index cases
      contacted, 108 (86.4%) agreed to provide information about partners. A total of
      199 sexual partners were identified (1.8 partners per interviewed index case).
      HIV outcome was already known for 58 partners (70.7% were known to be HIV
      positive), 141 partners were tested as result of partner notification, and 26
      were newly diagnosed with HIV. The case-finding effectiveness of the program was
      18.4%. CONCLUSION: This pilot program provides evidence of the effectiveness of a
      partner notification program implemented in healthcare settings. This active
      partner notification program was feasible, acceptable to the user, and identified
      a high proportion of HIV-infected patients previously unaware of their status.

PMID- 25849450
TI  - Catecholaminergic innervation of central and peripheral auditory circuitry varies
      with reproductive state in female midshipman fish, Porichthys notatus.
AB  - In seasonal breeding vertebrates, hormone regulation of catecholamines, which
      include dopamine and noradrenaline, may function, in part, to modulate behavioral
      responses to conspecific vocalizations. However, natural seasonal changes in
      catecholamine innervation of auditory nuclei is largely unexplored, especially in
      the peripheral auditory system, where encoding of social acoustic stimuli is
      initiated. The plainfin midshipman fish, Porichthys notatus, has proven to be an
      excellent model to explore mechanisms underlying seasonal peripheral auditory
      plasticity related to reproductive social behavior. Recently, we demonstrated
      robust catecholaminergic (CA) innervation throughout the auditory system in
      midshipman. Most notably, dopaminergic neurons in the diencephalon have
      widespread projections to auditory circuitry including direct innervation of the
      saccule, the main endorgan of hearing, and the cholinergic octavolateralis
      efferent nucleus (OE) which also projects to the inner ear. Here, we tested the
      hypothesis that gravid, reproductive summer females show differential CA
      innervation of the auditory system compared to non-reproductive winter females.
      We utilized quantitative immunofluorescence to measure tyrosine hydroxylase
      immunoreactive (TH-ir) fiber density throughout central auditory nuclei and the
      sensory epithelium of the saccule. Reproductive females exhibited greater density
      of TH-ir innervation in two forebrain areas including the auditory thalamus and
      greater density of TH-ir on somata and dendrites of the OE. In contrast, non
      reproductive females had greater numbers of TH-ir terminals in the saccule and
      greater TH-ir fiber density in a region of the auditory hindbrain as well as
      greater numbers of TH-ir neurons in the preoptic area. These data provide
      evidence that catecholamines may function, in part, to seasonally modulate the
      sensitivity of the inner ear and, in turn, the appropriate behavioral response to
      reproductive acoustic signals. 

PMID- 25849452
TI  - Redox-dependent chaperone/peroxidase function of 2-Cys-Prx from the
      cyanobacterium Anabaena PCC7120: role in oxidative stress tolerance.
AB  - BACKGROUND: Cyanobacteria, progenitors of plant chloroplasts, provide a suitable
      model system for plants to study adaptation towards different abiotic stresses.
      Genome of the filamentous, heterocystous, nitrogen-fixing cyanobacterium Anabaena
      PCC7120 harbours a single gene (alr4641) encoding a typical 2-Cys-Peroxiredoxins
      (2-Cys-Prxs). 2-Cys-Prxs are thiol-based peroxidases that also function as
      molecular chaperones in plants and other systems. The Alr4641 protein from
      Anabaena PCC7120 shows high level biochemical similarities with the plant 2-Cys
      Prx. The physiological role played by the Alr4641 protein in Anabaena was
      addressed in this study. RESULTS: In Anabaena PCC7120, alr4641 transcript
      /Alr4641 protein was induced in response to abiotic stresses and its promoter was
      active in the vegetative cells as well as heterocysts. The wild-type Alr4641
      protein or Alr4641 lacking the peroxidatic cysteine (Alr4641C56S) or the
      resolving cysteine (Alr4641C178S) existed as higher oligomers in their native
      form. The wild-type or the mutant Alr4641 proteins showed similar chaperone
      activity, but only the wild-type protein exhibited peroxidase activity indicating
      that unlike peroxidase activity, chaperone activity was not dependent on
      cysteines. In contrast to other 2-Cys-Prxs, chaperone/peroxidase activity of
      Alr4641 was dependent on its redox state and not oligomerization status. Alr4641
      could protect plasmid DNA from oxidative damage and physically associate with
      NADPH-dependent thioredoxin reductase (NTRC). Like 2-Cys-Prxs from plants (e.g.
      rice), Alr4641 could detoxify various peroxides using NTRC as reductant. On
      exposure to H2O2, recombinant Anabaena PCC7120 strain over-expressing Alr4641
      (An4641+) showed reduced content of reactive oxygen species (ROS), intact
      photosynthetic functions and consequently better survival than the wild-type
      Anabaena PCC7120, indicating that Alr4641 can protect Anabaena from oxidative
      stress. CONCLUSIONS: The peroxidase/chaperone function of Alr4641, its inherent
      transcriptional/translational induction under different abiotic stresses and
      localization in both vegetative cells and heterocysts could be an adaptive
      strategy to battle various oxidative stresses that Anabaena encounters during its
      growth. Moreover, the recombinant Anabaena strain over expressing Alr4641 showed
      higher resistance to oxidative stress, suggesting its potential to serve as
      stress-tolerant biofertilizers in rice fields.

PMID- 25849453
TI  - Ecdysteroids regulate the levels of Molt-Inhibiting Hormone (MIH) expression in
      the blue crab, Callinectes sapidus.
AB  - Arthropod molt is coordinated through the interplay between ecdysteroids and
      neuropeptide hormones. In crustaceans, changes in the activity of Y-organs during
      the molt cycle have been regulated by molt-inhibiting hormone (MIH) and
      crustacean hyperglycemic hormone (CHH). Little has been known of the mode of
      direct effects of ecdysteroids on the levels of MIH and CHH in the eyestalk
      ganglia during the molt cycle. This study focused on a putative feedback of
      ecdysteroids on the expression levels of MIH transcripts using in vitro
      incubation study with ecdysteroids and in vivo RNAi in the blue crab, Callinectes
      sapidus. Our results show a specific expression of ecdysone receptor (EcR) in
      which EcR1 is the major isoform in eyestalk ganglia. The initial elevation of MIH
      expression at the early premolt stages is replicated by in vitro incubations of
      eyestalk ganglia with ecdysteroids that mimic the intrinsic conditions of D0
      stage: the concentration (75 ng/ml) and composition (ponasterone A and 20
      hydroxyecdysone at a 3:1 (w:w) ratio). Additionally, multiple injections of EcR1
      dsRNA reduce MIH expression by 67%, compared to the controls. Our data provide
      evidence on a putative feedback mechanism of hormonal regulation during molting
      cycle, specifically how the molt cycle is repeated during the life cycle of
      crustaceans. The elevated concentrations of ecdysteroids at early premolt stage
      may act positively on the levels of MIH expression in the eyestalk ganglia.
      Subsequently, the increased MIH titers in the hemolymph at postmolt would inhibit
      the synthesis and release of ecdysteroids by Y-organs, resulting in re-setting
      the subsequent molt cycle. 

PMID- 25849454
TI  - Macrocyclic lactones differ in interaction with recombinant P-glycoprotein 9 of
      the parasitic nematode Cylicocylus elongatus and ketoconazole in a yeast growth
      assay.
AB  - Macrocyclic lactones (MLs) are widely used parasiticides against nematodes and
      arthropods, but resistance is frequently observed in parasitic nematodes of
      horses and livestock. Reports claiming resistance or decreased susceptibility in
      human nematodes are increasing. Since no target site directed ML resistance
      mechanisms have been identified, non-specific mechanisms were frequently
      implicated in ML resistance, including P-glycoproteins (Pgps, designated ABCB1 in
      vertebrates). Nematode genomes encode many different Pgps (e.g. 10 in the sheep
      parasite Haemonchus contortus). ML transport was shown for mammalian Pgps, Pgps
      on nematode egg shells, and very recently for Pgp-2 of H. contortus. Here, Pgp-9
      from the equine parasite Cylicocyclus elongatus (Cyathostominae) was expressed in
      a Saccharomyces cerevisiae strain lacking seven endogenous efflux transporters.
      Pgp was detected on these yeasts by flow cytometry and chemiluminescence using
      the monoclonal antibody UIC2, which is specific for the active Pgp conformation.
      In a growth assay, Pgp-9 increased resistance to the fungicides ketoconazole,
      actinomycin D, valinomycin and daunorubicin, but not to the anthelmintic
      fungicide thiabendazole. Since no fungicidal activity has been described for MLs,
      their interaction with Pgp-9 was investigated in an assay involving two drugs:
      Yeasts were incubated with the highest ketoconazole concentration not affecting
      growth plus increasing concentrations of MLs to determine competition between or
      modulation of transport of both drugs. Already equimolar concentrations of
      ivermectin and eprinomectin inhibited growth, and at fourfold higher ML
      concentrations growth was virtually abolished. Selamectin and doramectin did not
      increase susceptibility to ketoconazole at all, although doramectin has been
      shown previously to strongly interact with human and canine Pgp. An intermediate
      interaction was observed for moxidectin. This was substantiated by increased
      binding of UIC2 antibodies in the presence of ivermectin, moxidectin,
      daunorubicin and ketoconazole but not selamectin. These results demonstrate
      direct effects of MLs on a recombinant nematode Pgp in an ML-specific manner. 

PMID- 25849455
TI  - Xenotransplantation of human adipose-derived stem cells in zebrafish embryos.
AB  - Zebrafish is a widely used animal model with well-characterized background in
      developmental biology. The fate of human adipose-derived stem cells (ADSCs) after
      their xenotransplantation into the developing embryos of zebrafish is unknown.
      Therefore, human ADSCs were firstly isolated, and then transduced with lentiviral
      vector system carrying a green fluorescent protein (GFP) reporter gene, and
      followed by detection of their cell viability and the expression of cell surface
      antigens. These GFP-expressing human ADSCs were transplanted into the zebrafish
      embryos at 3.3-4.3 hour post-fertilization (hpf). Green fluorescent signal, the
      proliferation and differentiation of human ADSCs in recipient embryos were
      respectively examined using fluorescent microscopy and immunohistochemical
      staining. The results indicated that human ADSCs did not change their cell
      viability and the expression levels of cell surface antigens after GFP
      transduction. Microscopic examination demonstrated that green fluorescent signals
      of GFP expressed in the transplanted cells were observed in the embryos and larva
      fish at post-transplantation. The positive staining of Ki-67 revealed the
      survival and proliferation of human ADSCs in fish larvae after transplantation.
      The expression of CD105 was observable in the xenotransplanted ADSCs, but CD31
      expression was undetectable. Therefore, our results indicate that human ADSCs
      xenotransplanted in the zebrafish embryos not only can survive and proliferate at
      across-species circumstance, but also seem to maintain their undifferentiation
      status in a short term. This xenograft model of zebrafish embryos may provide a
      promising and useful technical platform for the investigation of biology and
      physiology of stem cells in vivo. 

PMID- 25849457
TI  - Newcastle disease virus (NDV) induces protein oxidation and nitration in brain
      and liver of chicken: Ameliorative effect of vitamin E.
AB  - The present study was aimed at investigating the therapeutic efficacy of vitamin
      E on oxidative injury in brain and liver of Newcastle disease virus (NDV)
      challenged chickens. We have analyzed the xanthine oxidase (XOD) activity; uric
      acid (UA) levels and superoxide radical generation by using electron spin
      resonance spectroscopy. Further, protein oxidation, nitration and apoptosis were
      evaluated in the brain and liver of the control, NDV-infected and NDV+Vit. E
      treated groups. A significant elevation was observed in XOD activity and UA
      levels in brain (p<0.001) and liver (p<0.05) of NDV infected birds when compared
      to controls. Further, significant increase in the production of superoxides,
      enhanced intracellular protein carbonyls and nitrates were observed in the brain
      and liver of NDV-infected birds over healthy subjects. Apoptosis studies also
      suggested that a larger number of TUNEL positive cells were observed in brain and
      a moderately in liver of NDV-infected chickens. However, all these perturbations
      were significantly ameliorated in NDV+Vit. E treated chickens as compared to NDV
      infected birds. Taken together, our results suggested that NDV-induced neuronal
      and hepatic damage at least in part mediates oxidative stress and on the other
      hand, supplementation of vitamin E mitigates NDV-induced oxidative damage thereby
      protects brain and liver of chickens. These findings could provide new insights
      into the understanding of NDV pathogenesis and therapeutic effects of dietary
      antioxidants. 

PMID- 25849458
TI  - Azadirachtin-induced apoptosis involves lysosomal membrane permeabilization and
      cathepsin L release in Spodoptera frugiperda Sf9 cells.
AB  - Azadirachtin as a kind of botanical insecticide has been widely used in pest
      control. We previously reported that azadirachtin could induce apoptosis of
      Spodoptera litura cultured cell line Sl-1, which involves in the up-regulation of
      P53 protein. However, the detailed mechanism of azadirachtin-induced apoptosis is
      not clearly understood in insect cultured cells. The aim of the present study was
      to address the involvement of lysosome and lysosomal protease in azadirachtin
      induced apoptosis in Sf9 cells. The result confirmed that azadirachtin indeed
      inhibited proliferation and induced apoptosis. The lysosomes were divided into
      different types as time-dependent manner, which suggested that changes of
      lysosomes were necessarily physiological processes in azadirachtin-induced
      apoptosis in Sf9 cells. Interestingly, we noticed that azadirachtin could trigger
      lysosomal membrane permeabilization and cathepsin L releasing to cytosol. Z-FF
      FMK (a cathepsin L inhibitor), but not CA-074me (a cathepsin B inhibitor), could
      effectively hinder the apoptosis induced by azadirachtin in Sf9 cells. Meanwhile,
      the activity of caspase-3 could also be inactivated by the inhibition of
      cathepsin L enzymatic activity induced by Z-FF-FMK. Taken together, our findings
      suggest that azadirachtin could induce apoptosis in Sf9 cells in a lysosomal
      pathway, and cathepsin L plays a pro-apoptosis role in this process through
      releasing to cytosol and activating caspase-3. 

PMID- 25849456
TI  - Features of two new proteins with OmpA-like domains identified in the genome
      sequences of Leptospira interrogans.
AB  - Leptospirosis is an acute febrile disease caused by pathogenic spirochetes of the
      genus Leptospira. It is considered an important re-emerging infectious disease
      that affects humans worldwide. The knowledge about the mechanisms by which
      pathogenic leptospires invade and colonize the host remains limited since very
      few virulence factors contributing to the pathogenesis of the disease have been
      identified. Here, we report the identification and characterization of two new
      leptospiral proteins with OmpA-like domains. The recombinant proteins, which
      exhibit extracellular matrix-binding properties, are called Lsa46 - LIC13479 and
      Lsa77 - LIC10050 (Leptospiral surface adhesins of 46 and 77 kDa, respectively).
      Attachment of Lsa46 and Lsa77 to laminin was specific, dose dependent and
      saturable, with KD values of 24.3 +/- 17.0 and 53.0 +/- 17.5 nM, respectively.
      Lsa46 and Lsa77 also bind plasma fibronectin, and both adhesins are plasminogen
      (PLG)-interacting proteins, capable of generating plasmin (PLA) and as such,
      increase the proteolytic ability of leptospires. The proteins corresponding to
      Lsa46 and Lsa77 are present in virulent L. interrogans L1-130 and in saprophyte
      L. biflexa Patoc 1 strains, as detected by immunofluorescence. The adhesins are
      recognized by human leptospirosis serum samples at the onset and convalescent
      phases of the disease, suggesting that they are expressed during infection. Taken
      together, our data could offer valuable information to the understanding of
      leptospiral pathogenesis. 

PMID- 25849459
TI  - Oxidative stress, mitochondrial perturbations and fetal programming of renal
      disease induced by maternal smoking.
AB  - An adverse in-utero environment is increasingly recognized to predispose to
      chronic disease in adulthood. Maternal smoking remains the most common modifiable
      adverse in-utero exposure leading to low birth weight, which is strongly
      associated with chronic kidney disease (CKD) in later life. In order to
      investigate underlying mechanisms for such susceptibility, female Balb/c mice
      were sham or cigarette smoke-exposed (SE) for 6 weeks before mating, throughout
      gestation and lactation. Offspring kidneys were examined for oxidative stress,
      expression of mitochondrial proteins, mitochondrial structure as well as renal
      functional parameters on postnatal day 1, day 20 (weaning) and week 13 (adult
      age). From birth throughout adulthood, SE offspring had increased renal levels of
      mitochondrial-derived reactive oxygen species (ROS), which left a footprint on
      DNA with increased 8-hydroxydeoxyguanosin (8-OHdG) in kidney tubular cells.
      Mitochondrial structural abnormalities were seen in SE kidneys at day 1 and week
      13 along with a reduction in oxidative phosphorylation (OXPHOS) proteins and
      activity of mitochondrial antioxidant Manganese superoxide dismutase (MnSOD).
      Smoke exposure also resulted in increased mitochondrial DNA copy number (day 1
      week 13) and lysosome density (day 1 and week 13). The appearance of
      mitochondrial defects preceded the onset of albuminuria at week 13. Thus,
      mitochondrial damage caused by maternal smoking may play an important role in
      development of CKD at adult life. 

PMID- 25849460
TI  - 1H NMR metabolic profiling of plasma reveals additional phenotypes in knockout
      mouse models.
AB  - The International Mouse Phenotyping Consortium program has been established to
      ascribe biological functions to systematically knocked-out (KO) genes by in vivo
      and ex vivo phenotyping. The plasma clinical chemistry screen includes an
      assessment of liver, kidney, and bone function and provides a basic lipid profile
      and histopathology reports on 32 tissues. We report on the inclusion of plasma
      analysis by proton nuclear magnetic resonance ((1)H NMR) spectroscopy. (1)H NMR
      spectroscopy data are summarized from 116 running baseline controls with 18
      homozygous and 2 heterozygous KO mouse lines along with wild-type controls
      (typically n = 7 per gender). For the baseline group, the intersample variation
      of (1)H NMR glucose measurement was 12%, and the (1)H NMR spectroscopy data were
      influenced by gender and feeding status. There were good correlations between the
      clinical chemistry and the (1)H NMR spectroscopy measurements for glucose,
      triglycerides, and HDL cholesterol. Significant differences were observed in two
      KO lines, Agl (MGI: 1924809) and Bbs5 (MGI: 1919819), by (1)H NMR spectroscopy,
      clinical chemistry, and histopathology. In a further two KO lines, Elmod1 (MGI:
      3583900) and Emc10 (MGI: 1916933), (1)H NMR metabolic differences were observed,
      but no other ex vivo changes were detected. In the remaining 16 lines, no ex vivo
      abnormal phenotypes were observed. Plasma (1)H NMR spectroscopy can therefore
      provide a novel perspective on the function of knocked-out genes. 

PMID- 25849461
TI  - Periodontitis and Porphyromonas gingivalis in preclinical stage of arthritis
      patients.
AB  - PURPOSE: To determine whether the presence of periodontitis (PD) and
      Porphyromonas gingivalis (Pg) in the subgingival biofilm associates with the
      development of rheumatoid arthritis (RA) in treatment naive preclinical stage of
      arthritis patients. METHODS: We conducted a prospective cohort study of 72
      consecutive patients with arthralgia who had never been treated with any anti
      rheumatic drugs or glucocorticoids. Periodontal status at baseline was assessed
      by dentists. PD was defined stringently by the maximal probing depth?4 mm, or by
      the classification by the 5th European Workshop in Periodontology (EWP) in 2005
      using attachment loss. Up to eight plaque samples were obtained from each patient
      and the presence of Pg was determined by Taqman PCR. The patients were followed
      up for 2 years and introduction rate of methotrexate (MTX) treatment on the
      diagnosis of RA was compared in patients with or without PD or Pg. RESULTS:
      Patients with PD (probing depth?4mm) had higher arthritis activity (p = 0.02) and
      higher risk for future introduction of MTX treatment on the diagnosis of RA
      during the follow up than patients without PD (Hazard ratio 2.68, p = 0.03).
      Arthritis activity and risk for MTX introduction increased with the severity of
      PD assessed by EWP, although not statistically significant. On the other hand,
      presence of Pg was not associated with arthritis activity (p = 0.72) or the risk
      for MTX introduction (p = 0.45). CONCLUSION: In treatment naive arthralgia
      patients, PD, but not the presence of Pg, associates with arthritis activity and
      future requirement of MTX treatment on the diagnosis of RA.

PMID- 25849462
TI  - Experimental determination of the membrane topology of the Plasmodium protease
      Plasmepsin V.
AB  - The malaria parasite exports hundreds of proteins into its host cell. The
      majority of exported proteins contain a Host-Targeting motif (also known as a
      Plasmodium export element) that directs them for export. Prior to export, the
      Host-Targeting motif is cleaved by the endoplasmic reticulum-resident protease
      Plasmepsin V and the newly generated N-terminus is N-alpha-acetylated by an
      unidentified enzyme. The cleaved, N-alpha-acetylated protein is trafficked to the
      parasitophorous vacuole, where it is translocated across the vacuole membrane. It
      is clear that cleavage and N-alpha-acetylation of the Host-Targeting motif occur
      at the endoplasmic reticulum, and it has been proposed that Host-Targeting motif
      cleavage and N-alpha-acetylation occur either on the luminal or cytosolic side of
      the endoplasmic reticulum membrane. Here, we use self-associating 'split'
      fragments of GFP to determine the topology of Plasmepsin V in the endoplasmic
      reticulum membrane; we show that the catalytic protease domain of Plasmepsin V
      faces the endoplasmic reticulum lumen. These data support a model in which the
      Host-Targeting motif is cleaved and N-alpha-acetylated in the endoplasmic
      reticulum lumen. Furthermore, these findings suggest that cytosolic N-alpha
      acetyltransferases are unlikely to be candidates for the N-alpha
      acetyltransferase of Host-Targeting motif-containing exported proteins. 

PMID- 25849463
TI  - Characterizing newly repopulated microglia in the adult mouse: impacts on animal
      behavior, cell morphology, and neuroinflammation.
AB  - Microglia are the primary immune cell in the brain and are postulated to play
      important roles outside of immunity. Administration of the dual colony
      stimulating factor 1 receptor (CSF1R)/c-Kit kinase inhibitor, PLX3397, to adult
      mice results in the elimination of ~99% of microglia, which remain eliminated for
      as long as treatment continues. Upon removal of the inhibitor, microglia rapidly
      repopulate the entire adult brain, stemming from a central nervous system (CNS)
      resident progenitor cell. Using this method of microglial elimination and
      repopulation, the role of microglia in both healthy and diseased states can be
      explored. Here, we examine the responsiveness of newly repopulated microglia to
      an inflammatory stimulus, as well as determine the impact of these cells on
      behavior, cognition, and neuroinflammation. Two month-old wild-type mice were
      placed on either control or PLX3397 diet for 21 d to eliminate microglia. PLX3397
      diet was then removed in a subset of animals to allow microglia to repopulate and
      behavioral testing conducted beginning at 14 d repopulation. Finally,
      inflammatory profiling of the microglia-repopulated brain in response to
      lipopolysaccharide (LPS; 0.25 mg/kg) or phosphate buffered saline (PBS) was
      determined 21 d after inhibitor removal using quantitative real time polymerase
      chain reaction (RT-PCR), as well as detailed analyses of microglial morphologies.
      We find mice with repopulated microglia to perform similarly to controls by
      measures of behavior, cognition, and motor function. Compared to control/resident
      microglia, repopulated microglia had larger cell bodies and less complex
      branching in their processes, which resolved over time after inhibitor removal.
      Inflammatory profiling revealed that the mRNA gene expression of repopulated
      microglia was similar to normal resident microglia and that these new cells
      appear functional and responsive to LPS. Overall, these data demonstrate that
      newly repopulated microglia function similarly to the original resident microglia
      without any apparent adverse effects in healthy adult mice. 

PMID- 25849464
TI  - Structural and functional roles of glycosylation in fungal laccase from Lentinus
      sp.
AB  - Laccases are multi-copper oxidases that catalyze the oxidation of various organic
      and inorganic compounds by reducing O2 to water. Here we report the crystal
      structure at 1.8 A resolution of a native laccase (designated nLcc4) isolated
      from a white-rot fungus Lentinus sp. nLcc4 is composed of three cupredoxin-like
      domains D1-D3 each folded into a Greek key beta-barrel topology. T1 and T2/T3
      copper binding sites and three N-glycosylated sites at Asn75, Asn238, and Asn458
      were elucidated. Initial rate kinetic analysis revealed that the kcat, Km, and
      kcat/Km of nLcc4 with substrate ABTS were 3,382 s-1, 65.0 +/- 6.5 MUM, and 52 s
      1MUM-1, respectively; and the values with lignosulfonic acid determined using
      isothermal titration calorimetry were 0.234 s-1, 56.7 +/- 3.2 MUM, and 0.004 s
      1MUM-1, respectively. Endo H-deglycosylated nLcc4 (dLcc4), with only one GlcNAc
      residue remaining at each of the three N-glycosylation sites in the enzyme,
      exhibited similar kinetic efficiency and thermal stability to that of nLcc4. The
      isolated Lcc4 gene contains an open reading frame of 1563 bp with a deduced
      polypeptide of 521 amino acid residues including a predicted signaling peptide of
      21 residues at the N-terminus. Recombinant wild-type Lcc4 and mutant enzymes
      N75D, N238D and N458D were expressed in Pichia pastoris cells to evaluate the
      effect on enzyme activity by single glycosylation site deficiency. The mutant
      enzymes secreted in the cultural media of P. pastoris cells were observed to
      maintain only 4-50% of the activity of the wild-type laccase. Molecular dynamics
      simulations analyses of various states of (de-)glycosylation in nLcc support the
      kinetic results and suggest that the local H-bond networks between the domain
      connecting loop D2-D3 and the glycan moieties play a crucial role in the laccase
      activity. This study provides new insights into the role of glycosylation in the
      structure and function of a Basidiomycete fungal laccase. 

PMID- 25849466
TI  - A heartfelt thank you to Dr Joel Weaver.

PMID- 25849465
TI  - Aspirin use and lung cancer risk: a possible relationship? Evidence from an
      updated meta-analysis.
AB  - BACKGROUND AND PURPOSE: Growing evidence has emerged and controversial results
      reported on possible relationship between aspirin use and lung cancer risk. We,
      therefore, conducted this updated and comprehensive meta-analysis to evaluate
      this issue, with focus on dose-risk and duration-risk relationships. METHODS: We
      searched electronic databases including PUBMED, EMBASE and Cochrane library to
      identify eligible studies. Relative risk (RR) and its 95% confidence interval
      (CI) were used for cohort studies, while odds ratio (OR) were employed for case
      control studies. The random effects and fixed effects models were used for
      analyses. RESULTS: 18 studies were identified including 19835 lung cancer cases,
      which were eligible for inclusion in the present meta-analysis. Pooled data from
      case-control studies showed a significant inverse association between regular
      aspirin use and lung cancer risk. But for cohort studies, insignificant
      association was detected with little evidence of heterogeneity (RR: 1.05, 95%CI:
      0.95 - 1.16; I2: 10.3%, p value: 0.351). In case-control studies, standard
      aspirin use (>325mg) was related to lower lung cancer incidence, compared with
      low-dose aspirin use (75-100mg). A similar trend was observed in cohort studies.
      Besides, when analysis was restricted to long time regular aspirin use (>5
      years), insignificant results were reported in both cohort and case-control
      studies. Finally, regular aspirin use might result in higher reduction of non
      small cell lung cancer incidence among men. CONCLUSIONS: Our findings do not
      support the protective effect of regular aspirin use on lung cancer risk. Long
      time aspirin use, sex, dose and type of lung cancer might alter the effect of
      aspirin use on lung cancer risk. More well-designed studies are needed to further
      clarify these associations.

PMID- 25849467
TI  - Effect of needle design on pain from dental local anesthetic injections.
AB  - The purpose of this randomized, double-blind clinical study was to evaluate the
      effectiveness of a larger-bore compared with a standard-bore dental local
      anesthetic needle of the same gauge in reducing pain during inferior alveolar
      (IA) and long buccal (LB) nerve block injections. Twenty active duty military or
      Department of Defense beneficiaries undergoing dental treatment were anesthetized
      using a split-mouth design with 4 anesthetic dental injections. Both sides of the
      mouth received IA nerve block and LB nerve injections, one using the 27-gauge
      large-bore Septoject XL needle and other using a 27-gauge standard-bore Septoject
      needle. Patients rated the pain experienced with each method using a visual
      analogue scale (VAS). The IA injection mean VAS score and standard deviation were
      38.9 +/- 22.7 mm and 37.1 +/- 22.4 mm, respectively, for the larger and standard
      bore needles. The LB injection mean VAS score and standard deviation were 33.5 +/
      22.8 mm and 35.1 +/- 19.6 mm, respectively, for the larger and standard-bore
      needles. The data were analyzed with a paired t test (alpha = .05). No
      significant difference was found between the IA (P = .70) or LB injections (P =
      .73). The use of a larger-bore 27-gauge needle did not reduce pain on injection
      compared with the standard-bore 27-gauge needle. 

PMID- 25849468
TI  - Independent predictors of delay in emergence from general anesthesia.
AB  - Some patients with intellectual disabilities spend longer than others in
      emergence from ambulatory general anesthesia for dental treatment. Although
      antiepileptic drugs and anesthetics might be involved, an independent predictor
      for delay of the emergence remains unclear. Thus, a purpose of this study is to
      identify independent factors affecting the delay of emergence from general
      anesthesia. This was a retrospective cohort study in dental patients with
      intellectual disabilities. Patients in need of sedative premedication were
      removed from participants. The outcome was time until emergence from general
      anesthesia. Stepwise multivariate regression analysis was used to extract
      independent factors affecting the outcome. Antiepileptic drugs and anesthetic
      parameters were included as predictor variables. The study included 102 cases.
      Clobazam, clonazepam, and phenobarbital were shown to be independent determinants
      of emergence time. Parameters relating to anesthetics, patients' backgrounds, and
      dental treatment were not independent factors. Delay in emergence time in
      ambulatory general anesthesia is likely to be related to the antiepileptic drugs
      of benzodiazepine or barbiturates in patients with intellectual disability. 

PMID- 25849469
TI  - Anesthetic efficacy of meperidine in teeth with symptomatic irreversible
      pulpitis.
AB  - Achieving adequate pulpal anesthesia in mandibular teeth is always a challenge.
      Supplementary injections and using drugs in combination are some methods
      implemented to overcome this hurdle. In this randomized clinical trial, use of
      meperidine in conjunction with lidocaine in intraligamentary injection did not
      exhibit significant improvement in anesthesia. 

PMID- 25849470
TI  - Anesthetic management by laryngeal mask airway in a patient with a history of
      difficult intubation resulting in dental injuries.
AB  - Disabled patients may face respiratory problems during general anesthesia because
      of head and neck anomalies. We describe a case of dental treatment under general
      anesthesia using a laryngeal mask airway in a disabled patient who faced
      difficulty in endotracheal intubation on several occasions, 5 of which resulted
      in dental injuries. 

PMID- 25849471
TI  - Suspected intraoperative anaphylaxis to gelatin absorbable hemostatic sponge.
AB  - Anaphylaxis under anesthesia is a life-threatening medical emergency that
      requires rapid identification and treatment. Allergies to agents with which the
      general population are likely to come into contact are usually identified, but
      patients are exposed to uncommon agents during anesthesia and surgery. Here, we
      describe a case of anaphylaxis under anesthesia implicating Gelfoam sponges. 

PMID- 25849472
TI  - Dexmedetomidine, ketamine, and midazolam for oral rehabilitation: a case report.
AB  - Intravenous sedation is frequently provided by anesthesiologists for phobic
      patients undergoing elective dental treatment in outpatient settings. Propofol is
      one of the most commonly used anesthetic agents that can result in apnea and
      respiratory depression, thereby posing potential difficulties with perioperative
      airway management. Dexmedetomidine has been utilized successfully in intravenous
      sedation for a wide variety of procedures and holds potential as an alternative
      to propofol in outpatient dental settings. However, as a single agent, it may not
      provide adequate depth of sedation and analgesia for oral rehabilitation. In this
      case report we demonstrate an effective alternative intravenous deep-sedation
      technique for an adult phobic patient undergoing oral rehabilitation utilizing 3
      agents in combination: dexmedetomidine, ketamine, and midazolam. This combination
      of agents may be especially useful for those patients with a history of substance
      abuse, where administration of opioids may be undesirable or contraindicated. 

PMID- 25849473
TI  - Alpha-2 adrenergic receptor agonists: a review of current clinical applications.
AB  - The alpha-2 adrenergic receptor agonists have been used for decades to treat
      common medical conditions such as hypertension; attention-deficit/hyperactivity
      disorder; various pain and panic disorders; symptoms of opioid, benzodiazepine,
      and alcohol withdrawal; and cigarette craving. (1) However, in more recent years,
      these drugs have been used as adjuncts for sedation and to reduce anesthetic
      requirements. This review will provide an historical perspective of this drug
      class, an understanding of pharmacological mechanisms, and an insight into
      current applications in clinical anesthesiology. 

PMID- 25849475
TI  - Reply: To PMID 25517557.

PMID- 25849477
TI  - Optimal cut-off points on the health anxiety inventory, illness attitude scales
      and whiteley index to identify severe health anxiety.
AB  - BACKGROUND: Health anxiety can be viewed as a dimensional phenomenon where severe
      health anxiety in form of DSM-IV hypochondriasis represents a cut-off where the
      health anxiety becomes clinically significant. Three of the most reliable and
      used self-report measures of health anxiety are the Health Anxiety Inventory
      (HAI), the Illness Attitude Scales (IAS) and the Whiteley Index (WI). Identifying
      the optimal cut-offs for classification of presence of a diagnosis of severe
      health anxiety on these measures has several advantages in clinical and research
      settings. The aim of this study was therefore to investigate the HAI, IAS and WI
      as proximal diagnostic instruments for severe health anxiety defined as DSM-IV
      hypochondriasis. METHODS: We investigated sensitivity, specificity and predictive
      value on the HAI, IAS and WI using a total of 347 adult participants of whom 158
      had a diagnosis of severe health anxiety, 97 had obsessive-compulsive disorder
      and 92 were healthy non-clinical controls. Diagnostic assessments were conducted
      using the Anxiety Disorder Interview Schedule. RESULTS: Optimal cut-offs for
      identifying a diagnosis of severe health anxiety was 67 on the HAI, 47 on the
      IAS, and 5 on the WI. Sensitivity and specificity were high, ranging from 92.6 to
      99.4%. Positive and negative predictive values ranged from 91.6 to 99.4% using
      unadjusted prevalence rates. CONCLUSIONS: The HAI, IAS and WI have very good
      properties as diagnostic indicators of severe health anxiety and can be used as
      cost-efficient proximal estimates of the diagnosis.

PMID- 25849478
TI  - SMY2 and SYH1 suppress defects in ribosome biogenesis caused by ebp2 mutations.
AB  - Ebp2 is an assembly factor of the 60S ribosomal subunit in yeast. We demonstrate
      that overexpression of SMY2 or SYH1 partially suppresses defects in growth and
      ribosome biogenesis of ebp2 mutants, and that smy2Delta and syh1Delta exhibit
      synthetic growth defects with the ebp2 allele. These results suggest that Smy2
      and Syh1 may be involved in ribosome biogenesis in relation to Ebp2.

PMID- 25849479
TI  - Global analysis of the Gossypium hirsutum L. Transcriptome during leaf senescence
      by RNA-Seq.
AB  - BACKGROUND: Leaf senescence is an important developmental programmed degeneration
      process that dramatically affects crop quality and yield. The regulation of
      senescence is highly complex. Although senescence regulatory genes have been well
      characterized in model species such as Arabidopsis and rice, there is little
      information on the control of this process in cotton. Here, the senescence
      process in cotton (Gossypium hirsutum L.) leaves was investigated over a time
      course including young leaf, mature leaf and leaf samples from different
      senescence stages using RNA-Seq. RESULTS: Of 24,846 genes detected by mapping the
      tags to Gossypium genomes, 3,624 genes were identified as differentially
      expressed during leaf senescence. There was some overlap between the genes
      identified here and senescence-associated genes previously identified in other
      species. Most of the genes related to photosynthesis, chlorophyll metabolism and
      carbon fixation were downregulated; whereas those for plant hormone signal
      transduction were upregulated. Quantitative real-time PCR was used to evaluate
      the results of RNA-Seq for gene expression profiles. Furthermore, 519
      differentially expressed transcription factors were identified, notably WRKY,
      bHLH and C3H. In addition, 960 genes involved in the metabolism and regulation of
      eight hormones were identified, of which many genes involved in the abscisic
      acid, brassinosteroid, jasmonic acid, salicylic acid and ethylene pathways were
      upregulated, indicating that these hormone-related genes might play crucial roles
      in cotton leaf development and senescence. However, most auxin, cytokinin and
      gibberellin pathway-related genes were downregulated, suggesting that these three
      hormones may act as negative regulators of senescence. CONCLUSIONS: This is the
      first high-resolution, multiple time-course, genome-wide comprehensive analysis
      of gene expression in cotton. These data are the most comprehensive dataset
      currently available for cotton leaf senescence, and will serve as a useful
      resource for unraveling the functions of many specific genes involved in cotton
      leaf development and senescence.

PMID- 25849480
TI  - Asthma, type 1 and type 2 diabetes mellitus, and inflammatory bowel disease
      amongst South Asian immigrants to Canada and their children: a population-based
      cohort study.
AB  - BACKGROUND: There is a high and rising rate of immune-mediated diseases in the
      Western world. Immigrants from South Asia have been reported to be at higher risk
      upon arrival to the West. We determined the risk of immune-mediated diseases in
      South Asian and other immigrants to Ontario, Canada, and their Ontario-born
      children. METHODS: Population-based cohorts of patients with asthma, type 1
      diabetes (T1DM), type 2 diabetes (T2DM), and inflammatory bowel disease (IBD)
      were derived from health administrative data. We determined the standardized
      incidence, and the adjusted risk of these diseases in immigrants from South Asia,
      immigrants from other regions, compared with non-immigrant residents of Ontario.
      The risk of these diseases in the Ontario-born children of immigrants were
      compared to the children of non-immigrants. RESULTS: Compared to non-immigrants,
      adults from South Asia had higher risk of asthma (IRR 1.56, 95%CI 1.51-1.61) and
      T2DM (IRR 2.59, 95%CI 2.53-2.65). Adults from South Asia had lower incidence of
      IBD than non-immigrants (IRR 0.32, 95%CI 0.22-0.49), as did immigrants from other
      regions (IRR 0.29, 95%CI 0.20-0.42). Compared to non-immigrant children, the
      incidence of asthma (IRR 0.66, 95%CI 0.62-0.71) and IBD (IRR 0.47, 95%CI 0.33
      0.67) was low amongst immigrant children from South Asia. However, the risk in
      Ontario-born children of South Asian immigrants relative to the children of non
      immigrants was higher for asthma (IRR 1.75, 95%CI 1.69-1.81) and less attenuated
      for IBD (IRR 0.90, 95%CI 0.65-1.22). CONCLUSION: Early-life environmental
      exposures may trigger a genetic predisposition to the development of asthma and
      IBD in South Asian immigrants and their Canada-born children.

PMID- 25849481
TI  - Gait mechanics in patients with chronic obstructive pulmonary disease.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by the
      frequent association of disease outside the lung. The objective of this study was
      to determine the presence of biomechanical gait abnormalities in COPD patients
      compared to healthy controls while well rested and without rest. METHODS:
      Patients with COPD (N = 17) and aged-matched, healthy controls (N = 21) walked at
      their self-selected pace down a 10-meter walkway while biomechanical gait
      variables were collected. A one-minute rest was given between each of the five
      collected trials to prevent tiredness (REST condition). Patients with COPD then
      walked at a self-selected pace on a treadmill until the onset of self-reported
      breathlessness or leg tiredness. Subjects immediately underwent gait analysis
      with no rest between each of the five collected trials (NO REST condition).
      Statistical models with and without covariates age, gender, and smoking history
      were used. RESULTS: After adjusting for covariates, COPD patients demonstrated
      more ankle power absorption in mid-stance (P = 0.006) than controls during both
      conditions. Both groups during NO REST demonstrated increased gait speed (P =
      0.04), stride length (P = 0.03), and peak hip flexion (P = 0.04) with decreased
      plantarflexion moment (P = 0.04) and increased knee power absorption (P = 0.04)
      as compared to REST. A significant interaction revealed that peak ankle
      dorsiflexion moment was maintained from REST to NO REST for COPD but increased
      for controls (P < 0.01). Stratifying by disease severity did not alter these
      findings, except that step width decreased in NO REST as compared to REST (P =
      0.01). Standardized effect sizes of significant effects varied from 0.5 to 0.98.
      CONCLUSIONS: Patients with COPD appear to demonstrate biomechanical gait changes
      at the ankle as compared to healthy controls. This was seen not only in increased
      peak ankle power absorption during no rest but was also demonstrated by a lack of
      increase in peak ankle dorsiflexion moment from the REST to the NO REST condition
      as compared to the healthy controls. Furthermore, a wider step width has been
      associated with fall risk and this could account for the increased incidence of
      falls in patients with COPD.

PMID- 25849483
TI  - A stock market forecasting model combining two-directional two-dimensional
      principal component analysis and radial basis function neural network.
AB  - In this paper, we propose and implement a hybrid model combining two-directional
      two-dimensional principal component analysis ((2D)2PCA) and a Radial Basis
      Function Neural Network (RBFNN) to forecast stock market behavior. First, 36
      stock market technical variables are selected as the input features, and a
      sliding window is used to obtain the input data of the model. Next, (2D)2PCA is
      utilized to reduce the dimension of the data and extract its intrinsic features.
      Finally, an RBFNN accepts the data processed by (2D)2PCA to forecast the next
      day's stock price or movement. The proposed model is used on the Shanghai stock
      market index, and the experiments show that the model achieves a good level of
      fitness. The proposed model is then compared with one that uses the traditional
      dimension reduction method principal component analysis (PCA) and independent
      component analysis (ICA). The empirical results show that the proposed model
      outperforms the PCA-based model, as well as alternative models based on ICA and
      on the multilayer perceptron. 

PMID- 25849482
TI  - Relaxin-3 receptor (RXFP3) signalling mediates stress-related alcohol preference
      in mice.
AB  - Stressful life events are causally linked with alcohol use disorders (AUDs),
      providing support for a hypothesis that alcohol consumption is aimed at stress
      reduction. We have previously shown that expression of relaxin-3 mRNA in rat
      brain correlates with alcohol intake and that central antagonism of relaxin-3
      receptors (RXFP3) prevents stress-induced reinstatement of alcohol-seeking.
      Therefore the objectives of these studies were to investigate the impact of Rxfp3
      gene deletion in C57BL/6J mice on baseline and stress-related alcohol
      consumption. Male wild-type (WT) and Rxfp3 knockout (KO) (C57/B6JRXFP3TM1/DGen)
      littermate mice were tested for baseline saccharin and alcohol consumption and
      preference over water in a continuous access two-bottle free-choice paradigm.
      Another cohort of mice was subjected to repeated restraint followed by swim
      stress to examine stress-related alcohol preference. Hepatic alcohol and aldehyde
      dehydrogenase activity was assessed in mice following chronic alcohol intake and
      in naive controls. WT and Rxfp3 KO mice had similar baseline saccharin and
      alcohol preference, and hepatic alcohol processing. However, Rxfp3 KO mice
      displayed a stress-induced reduction in alcohol preference that was not observed
      in WT littermates. Notably, this phenotype, once established, persisted for at
      least six weeks after cessation of stress exposure. These findings suggest that
      in mice, relaxin-3/RXFP3 signalling is involved in maintaining high alcohol
      preference during and after stress, but does not appear to strongly regulate the
      primary reinforcing effects of alcohol. 

PMID- 25849484
TI  - Potential role of Notch signalling in CD34+ chronic myeloid leukaemia cells:
      cross-talk between Notch and BCR-ABL.
AB  - Notch signalling is critical for haemopoietic stem cell (HSC) self-renewal and
      survival. The role of Notch signalling has been reported recently in chronic
      myeloid leukaemia (CML) - a stem cell disease characterized by BCR-ABL tyrosine
      kinase activation. Therefore, we studied the relationship between BCR-ABL and
      Notch signalling and assessed the expression patterns of Notch and its downstream
      target Hes1 in CD34+ stem and progenitor cells from chronic-phase CML patients
      and bone marrow (BM) from normal subjects (NBM). We found significant
      upregulation (p<0.05) of Notch1, Notch2 and Hes1 on the most primitive CD34+Thy+
      subset of CML CD34+ cells suggesting that active Notch signalling in CML
      primitive progenitors. In addition, Notch1 was also expressed in distinct
      lymphoid and myeloid progenitors within the CD34+ population of primary CML
      cells. To further delineate the possible role and interactions of Notch with BCR
      ABL in CD34+ primary cells from chronic-phase CML, we used P-crkl detection as a
      surrogate assay of BCR-ABL tyrosine kinase activity. Our data revealed that
      Imatinib (IM) induced BCR-ABL inhibition results in significant (p<0.05)
      upregulation of Notch activity, assessed by Hes1 expression. Similarly,
      inhibition of Notch leads to hyperactivation of BCR-ABL. This antagonistic
      relationship between Notch and BCR-ABL signalling was confirmed in K562 and ALL
      SIL cell lines. In K562, we further validated this antagonistic relationship by
      inhibiting histone deacetylase (HDAC) - an effector pathway of Hes1, using
      valproic acid (VPA) - a HDAC inhibitor. Finally, we also confirmed the potential
      antagonism between Notch and BCR/ABL in In Vivo, using publically available GSE
      database, by analysing gene expression profile of paired samples from chronic
      phase CML patients pre- and post-Imatinib therapy. Thus, we have demonstrated an
      antagonistic relationship between Notch and BCR-ABL in CML. A combined inhibition
      of Notch and BCR-ABL may therefore provide superior clinical response over
      tyrosine-kinase inhibitor monotherapy by targeting both quiescent leukaemic stem
      cells and differentiated leukaemic cells and hence must be explored. 

PMID- 25849485
TI  - Acrolein impairs the cholesterol transport functions of high density
      lipoproteins.
AB  - High density lipoproteins (HDL) are considered athero-protective, primarily due
      to their role in reverse cholesterol transport, where they transport cholesterol
      from peripheral tissues to the liver for excretion. The current study was
      designed to determine the impact of HDL modification by acrolein, a highly
      reactive aldehyde found in high abundance in cigarette smoke, on the cholesterol
      transport functions of HDL. HDL was chemically-modified with acrolein and
      immunoblot and mass spectrometry analyses confirmed apolipoprotein crosslinking,
      as well as acrolein adducts on apolipoproteins A-I and A-II. The ability of
      acrolein-modified HDL (acro-HDL) to serve as an acceptor of free cholesterol (FC)
      from COS-7 cells transiently expressing SR-BI was significantly decreased.
      Further, in contrast to native HDL, acro-HDL promotes higher neutral lipid
      accumulation in murine macrophages as judged by Oil Red O staining. The ability
      of acro-HDL to mediate efficient selective uptake of HDL-cholesteryl esters (CE)
      into SR-BI-expressing cells was reduced compared to native HDL. Together, the
      findings from our studies suggest that acrolein modification of HDL produces a
      dysfunctional particle that may ultimately promote atherogenesis by impairing
      functions that are critical in the reverse cholesterol transport pathway. 

PMID- 25849486
TI  - Interplay between constraints, objectives, and optimality for genome-scale
      stoichiometric models.
AB  - High-throughput data generation and genome-scale stoichiometric models have
      greatly facilitated the comprehensive study of metabolic networks. The
      computation of all feasible metabolic routes with these models, given
      stoichiometric, thermodynamic, and steady-state constraints, provides important
      insights into the metabolic capacities of a cell. How the feasible metabolic
      routes emerge from the interplay between flux constraints, optimality objectives,
      and the entire metabolic network of a cell is, however, only partially
      understood. We show how optimal metabolic routes, resulting from flux balance
      analysis computations, arise out of elementary flux modes, constraints, and
      optimization objectives. We illustrate our findings with a genome-scale
      stoichiometric model of Escherichia coli metabolism. In the case of one flux
      constraint, all feasible optimal flux routes can be derived from elementary flux
      modes alone. We found up to 120 million of such optimal elementary flux modes. We
      introduce a new computational method to compute the corner points of the optimal
      solution space fast and efficiently. Optimal flux routes no longer depend
      exclusively on elementary flux modes when we impose additional constraints; new
      optimal metabolic routes arise out of combinations of elementary flux modes. The
      solution space of feasible metabolic routes shrinks enormously when additional
      objectives---e.g. those related to pathway expression costs or pathway length--
      are introduced. In many cases, only a single metabolic route remains that is both
      feasible and optimal. This paper contributes to reaching a complete topological
      understanding of the metabolic capacity of organisms in terms of metabolic flux
      routes, one that is most natural to biochemists and biotechnologists studying and
      engineering metabolism. 

PMID- 25849487
TI  - Dual targeted therapy with p53 siRNA and Epigallocatechingallate in a triple
      negative breast cancer cell model.
AB  - Triple-negative breast cancer (TNBC) is a highly aggressive phenotype that is
      resistant to standard therapy. Thus, the development of alternative therapeutic
      strategies for TNBC is essential. The purpose of our in vitro study was to
      evaluate the impact of p53 gene silencing in conjunction with the administration
      of a natural compound, epigallocatechingallate (EGCG). RT2Profiler PCR Array
      technology was used to evaluate the impact of dual treatment on the main genes
      involved in apoptosis in the Hs578T cell culture model of TNBC. Gene expression
      analysis revealed 28 genes were significantly altered (16 upregulated and 12
      downregulated) in response to combined p53 siRNA and EGCG treatment. Further
      analysis revealed that p53 siRNA and EGCG dual therapy leads to the activation of
      pro-apoptotic genes and the inhibition of pro-survival genes, autophagy, and cell
      network formation. These results indicate that this dual therapy targets both the
      apoptotic and angiogenic pathways, which may improve treatment effectiveness for
      tumors resistant to conventional treatment. 

PMID- 25849488
TI  - Deep sequencing of the Trypanosoma cruzi GP63 surface proteases reveals diversity
      and diversifying selection among chronic and congenital Chagas disease patients.
AB  - BACKGROUND: Chagas disease results from infection with the diploid protozoan
      parasite Trypanosoma cruzi. T. cruzi is highly genetically diverse, and
      multiclonal infections in individual hosts are common, but little studied. In
      this study, we explore T. cruzi infection multiclonality in the context of age,
      sex and clinical profile among a cohort of chronic patients, as well as paired
      congenital cases from Cochabamba, Bolivia and Goias, Brazil using amplicon deep
      sequencing technology. METHODOLOGY/ PRINCIPAL FINDINGS: A 450bp fragment of the
      trypomastigote TcGP63I surface protease gene was amplified and sequenced across
      70 chronic and 22 congenital cases on the Illumina MiSeq platform. In addition, a
      second, mitochondrial target--ND5--was sequenced across the same cohort of cases.
      Several million reads were generated, and sequencing read depths were normalized
      within patient cohorts (Goias chronic, n = 43, Goias congenital n = 2, Bolivia
      chronic, n = 27; Bolivia congenital, n = 20), Among chronic cases, analyses of
      variance indicated no clear correlation between intra-host sequence diversity and
      age, sex or symptoms, while principal coordinate analyses showed no clustering by
      symptoms between patients. Between congenital pairs, we found evidence for the
      transmission of multiple sequence types from mother to infant, as well as
      widespread instances of novel genotypes in infants. Finally, non-synonymous to
      synonymous (dn:ds) nucleotide substitution ratios among sequences of TcGP63Ia and
      TcGP63Ib subfamilies within each cohort provided powerful evidence of strong
      diversifying selection at this locus. CONCLUSIONS/SIGNIFICANCE: Our results shed
      light on the diversity of parasite DTUs within each patient, as well as the
      extent to which parasite strains pass between mother and foetus in congenital
      cases. Although we were unable to find any evidence that parasite diversity
      accumulates with age in our study cohorts, putative diversifying selection within
      members of the TcGP63I gene family suggests a link between genetic diversity
      within this gene family and survival in the mammalian host.

PMID- 25849490
TI  - A novel system for evaluating drought-cold tolerance of grapevines using
      chlorophyll fluorescence.
AB  - BACKGROUND: Grape production in continental climatic regions suffers from the
      combination of drought and cold stresses during winter. Developing a reliable
      system to simulate combined drought-cold stress and to determine physiological
      responses and regulatory mechanisms is important. Evaluating tolerance to
      combined stress at germplasm level is crucial to select parents for breeding
      grapevines. RESULTS: In the present study, two species, namely, Vitis amurensis
      and V. vinifera cv. 'Muscat Hamburg', were used to develop a reliable system for
      evaluating their tolerance to drought-cold stress. This system used tissue 
      cultured grapevine plants, 6% PEG solution, and gradient cooling mode to simulate
      drought-cold stress. V. amurensis had a significantly lower LT50 value (the
      temperature of 50% electrolyte leakage) than 'Muscat Hamburg' during simulated
      drought-cold stress. Thus, the former had higher tolerance than the latter to
      drought-cold stress based on electrolyte leakage (EL) measurements. Moreover, the
      chlorophyll fluorescence responses of V. amurensis and 'Muscat Hamburg' were also
      analyzed under drought-cold stress. The maximum photochemical quantum yield of PS
      II (Fv/Fm) exhibited a significant linear correlationship with EL. The
      relationship of EL with Fv/Fm in the other four genotypes of grapevines under
      drought-cold stress was also detected. CONCLUSIONS: A novel LT50 estimation model
      was established, and the LT50 values can be well calculated based on Fv/Fm in
      replacement of EL measurement. The Fv/Fm-based model exhibits good reliability
      for evaluating the tolerance of different grapevine genotypes to drought-cold
      stress.

PMID- 25849491
TI  - Design and synthesis of fluorinated dendrimers for sensitive (19)F MRI.
AB  - To achieve high sensitivity for (19)F MRI, a class of novel dendritic molecules
      with multiple pseudosymmetrical fluorines was designed and efficiently
      synthesized. Through iterative bromination and Williamson ether synthesis under
      mild conditions, a fluorinated dendrimer with 540 pseudosymmetrical fluorines was
      conveniently prepared without performing the group protection in a convergent
      way. The dendrimer is characterized by a strong (19)F NMR peak and short
      relaxation times. Eventually, an appreciably enhanced (19)F MRI at an extremely
      low concentration (18.5 MUM) was achieved, which demonstrated the potential
      utility of such dendritic molecules in highly sensitive (19)F MRI. 

PMID- 25849489
TI  - Accounting for dependence induced by weighted KNN imputation in paired samples,
      motivated by a colorectal cancer study.
AB  - Missing data can arise in bioinformatics applications for a variety of reasons,
      and imputation methods are frequently applied to such data. We are motivated by a
      colorectal cancer study where miRNA expression was measured in paired tumor
      normal samples of hundreds of patients, but data for many normal samples were
      missing due to lack of tissue availability. We compare the precision and power
      performance of several imputation methods, and draw attention to the statistical
      dependence induced by K-Nearest Neighbors (KNN) imputation. This imputation
      induced dependence has not previously been addressed in the literature. We
      demonstrate how to account for this dependence, and show through simulation how
      the choice to ignore or account for this dependence affects both power and type I
      error rate control. 

PMID- 25849492
TI  - Multishell Au/Ag/SiO2 nanorods with tunable optical properties as single particle
      orientation and rotational tracking probes.
AB  - Three-layer core-shell plasmonic nanorods (Au/Ag/SiO2-NRs), consisting of a gold
      nanorod core, a thin silver shell, and a thin silica layer, were synthesized and
      used as optical imaging probes under a differential interference contrast
      microscope for single particle orientation and rotational tracking. The localized
      surface plasmon resonance modes were enhanced upon the addition of the silver
      shell, and the anisotropic optical properties of gold nanorods were maintained.
      The silica coating enables surface functionalization with silane coupling agents
      and provides enhanced stability and biocompatibility. Taking advantage of the
      longitudinal LSPR enhancement, the orientation and rotational information of the
      hybrid nanorods on synthetic lipid bilayers and on live cell membranes were
      obtained with millisecond temporal resolution using a scientific complementary
      metal-oxide-semiconductor camera. The results demonstrate that the as-synthesized
      hybrid nanorods are promising imaging probes with improved sensitivity and good
      biocompatibility for single plasmonic particle tracking experiments in biological
      systems. 

PMID- 25849493
TI  - Large-volume protein crystal growth for neutron macromolecular crystallography.
AB  - Neutron macromolecular crystallography (NMC) is the prevailing method for the
      accurate determination of the positions of H atoms in macromolecules. As neutron
      sources are becoming more available to general users, finding means to optimize
      the growth of protein crystals to sizes suitable for NMC is extremely important.
      Historically, much has been learned about growing crystals for X-ray diffraction.
      However, owing to new-generation synchrotron X-ray facilities and sensitive
      detectors, protein crystal sizes as small as in the nano-range have become
      adequate for structure determination, lessening the necessity to grow large
      crystals. Here, some of the approaches, techniques and considerations for the
      growth of crystals to significant dimensions that are now relevant to NMC are
      revisited. These include experimental strategies utilizing solubility diagrams,
      ripening effects, classical crystallization techniques, microgravity and
      theoretical considerations. 

PMID- 25849494
TI  - The X-ray structure of human P-cadherin EC1-EC2 in a closed conformation provides
      insight into the type I cadherin dimerization pathway.
AB  - Cadherins are a large family of calcium-dependent proteins that mediate cellular
      adherens junction formation and tissue morphogenesis. To date, the most studied
      cadherins are those classified as classical, which are further divided into type
      I or type II depending on selected sequence features. Unlike other members of the
      classical cadherin family, a detailed structural characterization of P-cadherin
      has not yet been fully obtained. Here, the high-resolution crystal structure
      determination of the closed form of human P-cadherin EC1-EC2 is reported. The
      structure shows a novel, monomeric packing arrangement that provides a further
      snapshot in the yet-to-be-achieved complete description of the highly dynamic
      cadherin dimerization pathway. Moreover, this is the first multidomain cadherin
      fragment to be crystallized and structurally characterized in its closed
      conformation that does not carry any extra N-terminal residues before the
      naturally occurring aspartic acid at position 1. Finally, two clear alternate
      conformations are observed for the critical Trp2 residue, suggestive of a
      transient, metastable state. The P-cadherin structure and packing arrangement
      shown here provide new and valuable information towards the complete structural
      characterization of the still largely elusive cadherin dimerization pathway. 

PMID- 25849495
TI  - Structural basis of the substrate specificity of the FPOD/FAOD family revealed by
      fructosyl peptide oxidase from Eupenicillium terrenum.
AB  - The FAOD/FPOD family of proteins has the potential to be useful for the longterm
      detection of blood glucose levels in diabetes patients. A bottleneck for this
      application is to find or engineer a FAOD/FPOD family enzyme that is specifically
      active towards alpha-fructosyl peptides but is inactive towards other types of
      glycated peptides. Here, the crystal structure of fructosyl peptide oxidase from
      Eupenicillium terrenum (EtFPOX) is reported at 1.9 A resolution. In contrast to
      the previously reported structure of amadoriase II, EtFPOX has an open substrate
      entrance to accommodate the large peptide substrate. The functions of residues
      critical for substrate selection are discussed based on structure comparison and
      sequence alignment. This study reveals the first structural details of group I
      FPODs that prefer alpha-fructosyl substrates and could provide significant useful
      information for uncovering the mechanism of substrate specificity of FAOD/FPODs
      and guidance towards future enzyme engineering for diagnostic purposes. 

PMID- 25849496
TI  - Crystallization and preliminary X-ray crystallographic analysis of the sclerostin
      neutralizing Fab AbD09097.
AB  - The secreted cystine-knot protein sclerostin was first identified from genetic
      screening of patients suffering from the rare bone-overgrowth diseases
      sclerosteosis and van Buchem disease. Sclerostin acts a negative regulator of
      bone growth through inhibiting the canonical Wnt signalling cascade by binding to
      and blocking the Wnt co-receptor LRP5/6. Its function in blocking
      osteoblastogenesis makes it an important target for osteoanabolic therapy
      approaches to treat osteoporosis, which is characterized by a progressive
      decrease in bone mass and density. In this work, the production, crystallization
      and preliminary X-ray diffraction data analysis of a sclerostin-neutralizing
      human Fab antibody fragment, AbD09097, obtained from a naive antibody library are
      reported. Crystals of the Fab AbD09097 belonged to space group P21, with unit
      cell parameters a = 45.19, b = 78.49, c = 59.20 A, beta = 95.71 degrees  and
      diffracted X-rays to a resolution of 1.8 A. 

PMID- 25849497
TI  - Crystallization and preliminary X-ray diffraction analysis of the interaction of
      Aeromonas hydrophila MtaN-1 with S-adenosylhomocysteine.
AB  - Prokaryotic 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase (MtaN) is
      a multifunctional enzyme that can hydrolyze S-adenosyl-L-homocysteine (SAH) and S
      methyl-5'-thioadenosine (MTA) to give S-ribosyl-L-homocysteine (SRH) and S-methyl
      5'-thioribose (MTR), respectively. This reaction plays a key role in several
      metabolic pathways, including biological methylation, polyamine biosynthesis,
      methionine recycling and bacterial quorum sensing. Structurally, MtaN belongs to
      the MtnN subfamily of the purine nucleoside phosphorylase (PNP)/uridine
      phosphorylase (UDP) phosphorylase family. Aeromonas hydrophila has two MtnN
      subfamily proteins: MtaN-1, a periplasmic protein with an N-terminal signal
      sequence, and MtaN-2, a cytosolic protein. In this study, MtaN-1 from Aeromonas
      hydrophila was successfully expressed and purified using Ni-NTA affinity, Q anion
      exchange and gel-filtration chromatography. Crystals of the protein in complex
      with the substrate SAH were obtained and diffracted to a resolution of 1.4 A. The
      crystals belonged to the trigonal space group P3121 or P3221, with unit-cell
      parameters a = b = 102.7, c = 118.8 A. The asymmetric unit contained two
      molecules of MtaN-1 complexed with SAH.

PMID- 25849498
TI  - Crystallization and preliminary X-ray diffraction analysis of an endo-1,4-beta-D
      glucanase from Aspergillus aculeatus F-50.
AB  - Cellulose is the most abundant renewable biomass on earth, and its decomposition
      has proven to be very useful in a wide variety of industries. Endo-1,4-beta-D
      glucanase (EC 3.2.1.4; endoglucanase), which can catalyze the random hydrolysis
      of beta-1,4-glycosidic bonds to cleave cellulose into smaller fragments, is a key
      cellulolytic enzyme. An endoglucanase isolated from Aspergillus aculeatus F-50
      (FI-CMCase) that was classified into glycoside hydrolase family 12 has been found
      to be effectively expressed in the industrial strain Pichia pastoris. Here,
      recombinant FI-CMCase was crystallized. Crystals belonging to the orthorhombic
      space group C2221, with unit-cell parameters a = 74.2, b = 75.1, c = 188.4 A,
      were obtained by the sitting-drop vapour-diffusion method and diffracted to 1.6 A
      resolution. Initial phase determination by molecular replacement clearly shows
      that the crystal contains two protein molecules in the asymmetric unit. Further
      model building and structure refinement are in progress.

PMID- 25849499
TI  - Purification, crystallization and preliminary X-ray analysis of the periplasmic
      haem-binding protein HutB from Vibrio cholerae.
AB  - The mechanism of haem transport across the inner membrane of pathogenic bacteria
      is currently insufficiently understood at the molecular level and no information
      is available for this process in Vibrio cholerae. To obtain structural insights
      into the periplasmic haem-binding protein HutB from V. cholerae (VcHutB), which
      is involved in haem transport through the HutBCD haem-transport system, at the
      atomic level, VcHutB was cloned, overexpressed and crystallized using 1.6 M
      ammonium sulfate as a precipitant at pH 7.0. X-ray diffraction data were
      collected to 2.4 A resolution on the RRCAT PX-BL-21 beamline at the Indus-2
      synchrotron, Indore, India. The crystals belonged to space group P43212, with
      unit-cell parameters a = b = 62.88, c = 135.8 A. Matthews coefficient
      calculations indicated the presence of one monomer in the asymmetric unit, with
      an approximate solvent content of 45.02%. Molecular-replacement calculations with
      Phaser confirmed the presence of a monomer in the asymmetric unit.

PMID- 25849500
TI  - Crystallization of mutants of Turnip yellow mosaic virus protease/ubiquitin
      hydrolase designed to prevent protease self-recognition.
AB  - Processing of the polyprotein of Turnip yellow mosaic virus is mediated by the
      protease PRO. PRO cleaves at two places, one of which is at the C-terminus of the
      PRO domain of another polyprotein molecule. In addition to this processing
      activity, PRO possesses an ubiquitin hydrolase (DUB) activity. The crystal
      structure of PRO has previously been reported in its polyprotein-processing mode
      with the C-terminus of one PRO inserted into the catalytic site of the next PRO,
      generating PRO polymers in the crystal packing of the trigonal space group. Here,
      two mutants designed to disrupt specific PRO-PRO interactions were generated,
      produced and purified. Crystalline plates were obtained by seeding and cross
      seeding from initial 'sea urchin'-like microcrystals of one mutant. The plates
      diffracted to beyond 2 A resolution at a synchrotron source and complete data
      sets were collected for the two mutants. Data processing and analysis indicated
      that both mutant crystals belonged to the same monoclinic space group, with two
      molecules of PRO in the asymmetric unit. 

PMID- 25849501
TI  - Cloning, expression, crystallization and preliminary X-ray studies of a
      superfolder GFP fusion of cyanobacterial Psb32.
AB  - A fusion of Psb32 from the thermophilic cyanobacterium Thermosynechococcus
      elongatus BP-1 (TePsb32) with superfolder GFP was created for enhanced solubility
      and improved detection and purification. The fusion protein readily formed large
      hexagonal crystals belonging to space group P6122. A full data set extending to
      2.3 A resolution was collected at the Swiss Light Source. The phase problem could
      be solved by using only the sfGFP fusion partner or by using GFP and AtTLP18.3
      from Arabidopsis thaliana as search models. Based on this expression construct, a
      versatile library of 24 vectors combining four different superfolder GFP variants
      and three affinity tags was generated to facilitate expression and screening of
      fluorescent fusion proteins.

PMID- 25849502
TI  - Crystallization and preliminary X-ray characterization of the eukaryotic
      replication terminator Reb1-Ter DNA complex.
AB  - The Reb1 protein from Schizosaccharomyces pombe is a member of a family of
      proteins that control programmed replication termination and/or transcription
      termination in eukaryotic cells. These events occur at naturally occurring
      replication fork barriers (RFBs), where Reb1 binds to termination (Ter) DNA sites
      and coordinates the polar arrest of replication forks and transcription
      approaching in opposite directions. The Reb1 DNA-binding and replication
      termination domain was expressed in Escherichia coli, purified and crystallized
      in complex with a 26-mer DNA Ter site. Batch crystallization under oil was
      required to produce crystals of good quality for data collection. Crystals grew
      in space group P21, with unit-cell parameters a = 68.9, b = 162.9, c = 71.1 A,
      beta = 94.7 degrees . The crystals diffracted to a resolution of 3.0 A. The
      crystals were mosaic and required two or three cycles of annealing. This study is
      the first to yield structural information about this important family of proteins
      and will provide insights into the mechanism of replication and transcription
      termination.

PMID- 25849503
TI  - Structure of the omalizumab Fab.
AB  - Omalizumab is a humanized anti-IgE antibody that inhibits the binding of IgE to
      its receptors on mast cells and basophils, thus blocking the IgE-mediated release
      of inflammatory mediators from these cells. Omalizumab binds to the Fc domains of
      IgE in proximity to the binding site of the high-affinity IgE receptor FcERI, but
      the epitope and the mechanisms and conformations governing the recognition remain
      unknown. In order to elucidate the molecular mechanism of its anti-IgE activity,
      the aim was to analyse the interaction of omalizumab with human IgE. Therefore,
      IgE Fc CE2-4 was recombinantly produced in mammalian HEK-293 cells. Functionality
      of the IgE Fc was proven by ELISA and mediator-release assays. Omalizumab IgG was
      cleaved with papain and the resulting Fab was purified by ion-exchange
      chromatography. The complex of IgE Fc with omalizumab was prepared by size
      exclusion chromatography. However, crystals containing the complex were not
      obtained, suggesting that the process of crystallization favoured the
      dissociation of the two proteins. Instead, two structures of the omalizumab Fab
      with maximum resolutions of 1.9 and 3.0 A were obtained. The structures reveal
      the arrangement of the CDRs and the position of omalizumab residues known from
      prior functional studies to be involved in IgE binding. Thus, the structure of
      omalizumab provides the structural basis for understanding the function of
      omalizumab, allows optimization of the procedure for complex crystallization and
      poses questions about the conformational requirements for anti-IgE activity. 

PMID- 25849504
TI  - Expression, purification, crystallization and preliminary crystallographic
      analysis of a GH20 beta-N-acetylglucosaminidase from the marine bacterium Vibrio
      harveyi.
AB  - Vibrio harveyi beta-N-acetylglucosaminidase (VhGlcNAcase) is a new member of the
      GH20 glycoside hydrolase family responsible for the complete degradation of
      chitin fragments, with N-acetylglucosamine (GlcNAc) monomers as the final
      products. In this study, the crystallization and preliminary crystallographic
      data of wild-type VhGlcNAcase and its catalytically inactive mutant D437A in the
      absence and the presence of substrate are reported. Crystals of wild-type
      VhGlcNAcase were grown in 0.1 M sodium acetate pH 4.6, 1.4 M sodium malonate,
      while crystals of the D437A mutant were obtained in 0.1 M bis-tris pH 7.5, 0.1 M
      sodium acetate, 20% PEG 3350. X-ray data from the wild-type and the mutant
      crystals were collected at a synchrotron-radiation light source and were complete
      to a resolution of 2.5 A. All crystals were composed of the same type of dimer,
      with the substrate N,N'-diacetylglucosamine (GlcNAc2 or diNAG) used for soaking
      was cleaved by the active enzyme, leaving only a single GlcNAc molecule bound to
      the protein.

PMID- 25849505
TI  - Purification, crystallization and preliminary X-ray crystallographic analysis of
      the phosphatase domain (PA3346PD) of the response regulator PA3346 from
      Pseudomonas aeruginosa PAO1.
AB  - The phosphatase domain (PA3346PD) of the response regulator PA3346 modulates the
      downstream anti-anti-sigma factor PA3347 to regulate swarming motility in
      Pseudomonas aeruginosa PAO1. PA3346PD, which comprises the protein phosphatase 2C
      domain (PP2C), is classified as a Ser/Thr phosphatase of the Mg(2+)- or Mn(2+)
      dependent protein phosphatase (PPM) family. The recombinant PA3346PD, with
      molecular mass 26 kDa, was overexpressed in Escherichia coli, purified on an
      Ni(2+)-NTA agarose column and crystallized by the sitting-drop vapour-diffusion
      method. X-ray diffraction data were collected from PA3346PD crystals to a
      resolution of 2.58 A and the crystals belonged to space group I4132 or I4332,
      with unit-cell parameter a = 157.61 A. Preliminary analysis indicates the
      presence of a monomer of PA3346PD in the asymmetric unit with a solvent content
      of 58.4%.

PMID- 25849506
TI  - Complex assembly, crystallization and preliminary X-ray crystallographic analysis
      of the human Rod-Zwilch-ZW10 (RZZ) complex.
AB  - The spindle-assembly checkpoint (SAC) monitors kinetochore-microtubule attachment
      during mitosis. In metazoans, the three-subunit Rod-Zwilch-ZW10 (RZZ) complex is
      a crucial SAC component that interacts with additional SAC-activating and SAC
      silencing components, including the Mad1-Mad2 complex and cytoplasmic dynein. The
      RZZ complex contains two copies of each subunit and has a predicted molecular
      mass of ~800 kDa. Given the low abundance of the RZZ complex in natural sources,
      its recombinant reconstitution was attempted by co-expression of its subunits in
      insect cells. The RZZ complex was purified to homogeneity and subjected to
      systematic crystallization attempts. Initial crystals containing the entire RZZ
      complex were obtained using the sitting-drop method and were subjected to
      optimization to improve the diffraction resolution limit. The crystals belonged
      to space group P31 (No. 144) or P32 (No. 145), with unit-cell parameters a = b =
      215.45, c = 458.7 A, alpha = beta = 90.0, gamma = 120.0 degrees .

PMID- 25849507
TI  - Structure of the ABL2/ARG kinase in complex with dasatinib.
AB  - ABL2/ARG (ABL-related gene) belongs to the ABL (Abelson tyrosine-protein kinase)
      family of tyrosine kinases. ARG plays important roles in cell morphogenesis,
      motility, growth and survival, and many of these biological roles overlap with
      the cellular functions of the ABL kinase. Chronic myeloid leukemia (CML) is
      associated with constitutive ABL kinase activation resulting from fusion between
      parts of the breakpoint cluster region (BCR) and ABL1 genes. Similarly, fusion of
      the ETV6 (Tel) and ARG genes drives some forms of T-cell acute lymphoblastic
      leukemia (T-ALL) and acute myeloid leukemia (AML). Dasatinib is a tyrosine kinase
      inhibitor used for the treatment of CML by inhibiting ABL, and while it also
      inhibits ARG, there is currently no structure of ARG in complex with dasatinib.
      Here, the co-crystal structure of the mouse ARG catalytic domain with dasatinib
      at 2.5 A resolution is reported. Dasatinib-bound ARG is found in the DFG-in
      conformation although it is nonphosphorylated on the activation-loop tyrosine. In
      this structure the glycine-rich P-loop is found in a relatively open conformation
      compared with other known ABL family-inhibitor complex structures. 

PMID- 25849508
TI  - Structure of dihydrodipicolinate synthase from the commensal bacterium
      Bacteroides thetaiotaomicron at 2.1 A resolution.
AB  - Dihydrodipicolinate synthase (DapA) catalyzes the first committed step of the
      diaminopimelate biosynthetic pathway of lysine. It has been shown to be an
      essential enzyme in many bacteria and has been the subject of research to
      generate novel antibiotics. However, this pathway is present in both pathogenic
      and commensal bacteria, and antibiotics targeting DapA may interfere with normal
      gut colonization. Bacteroides thetaiotaomicron is a Gram-negative commensal
      bacterium that makes up a large proportion of the normal microbiota of the human
      gut. The structure of DapA from B. thetaiotaomicron (BtDapA) has been determined.
      This structure will help to guide the generation of selectively active antibiotic
      compounds targeting DapA. 

PMID- 25849509
TI  - Analytical ultracentrifugation and preliminary X-ray studies of the chloroplast
      envelope quinone oxidoreductase homologue from Arabidopsis thaliana.
AB  - Quinone oxidoreductases reduce a broad range of quinones and are widely
      distributed among living organisms. The chloroplast envelope quinone
      oxidoreductase homologue (ceQORH) from Arabidopsis thaliana binds NADPH, lacks a
      classical N-terminal and cleavable chloroplast transit peptide, and is
      transported through the chloroplast envelope membrane by an unknown alternative
      pathway without cleavage of its internal chloroplast targeting sequence. To
      unravel the fold of this targeting sequence and its substrate specificity, ceQORH
      from A. thaliana was overexpressed in Escherichia coli, purified and
      crystallized. Crystals of apo ceQORH were obtained and a complete data set was
      collected at 2.34 A resolution. The crystals belonged to space group C2221, with
      two molecules in the asymmetric unit.

PMID- 25849510
TI  - Crystallization and preliminary X-ray analysis of four cysteine proteases from
      Ficus carica latex.
AB  - The latex of the common fig (Ficus carica) contains a mixture of at least five
      cysteine proteases commonly known as ficins (EC 3.4.22.3). Four of these
      proteases were purified to homogeneity and crystals were obtained in a variety of
      conditions. The four ficin (iso)forms appear in ten different crystal forms. All
      diffracted to better than 2.10 A resolution and for each form at least one
      crystal form diffracted to 1.60 A resolution or higher. Ficin (iso)forms B and C
      share a common crystal form, suggesting close sequence and structural similarity.
      The latter diffracted to a resolution of 1.20 A and belonged to space group P3121
      or P3221, with unit-cell parameters a = b = 88.9, c = 55.9 A.

PMID- 25849511
TI  - Cloning, expression, purification, crystallization and preliminary X-ray
      diffraction analysis of AerF from Microcystis aeruginosa, a putative reductase
      participating in aeruginosin biosynthesis.
AB  - The 2-carboxy-6-hydroxyoctahydroindole moiety is an essential residue for the
      antithrombotic activity of aeruginosins, which are a class of cyanobacteria
      derived bioactive linear tetrapeptides. The biosynthetic pathway of the 2-carboxy
      6-hydroxyoctahydroindole moiety has not yet been resolved. AerF was indicated to
      be involved in the biosynthesis of the 2-carboxy-6-hydroxyoctahydroindole moiety.
      This study reports the cloning, expression, purification, crystallization and
      preliminary X-ray diffraction analysis of AerF from Microcystis aeruginosa with a
      C-terminal His6 tag. The crystal diffracted to a maximum resolution of 1.38 A and
      belonged to the tetragonal space group P4322, with unit-cell parameters a = b =
      101.581, c = 116.094 A. The calculated Matthews coefficient and solvent content
      of the crystal were 2.47 A(3) Da(-1) and 50.32%, respectively. The initial model
      of the structure was obtained by the molecular-replacement method and refinement
      of the structure is in progress. 

PMID- 25849512
TI  - Serendipitous crystallization and structure determination of cyanase (CynS) from
      Serratia proteamaculans.
AB  - Cyanate hydratase (CynS) catalyzes the decomposition of cyanate and bicarbonate
      into ammonia and carbon dioxide. Here, the serendipitous crystallization of CynS
      from Serratia proteamaculans (SpCynS) is reported. SpCynS was crystallized as an
      impurity and its identity was determined using mass-spectrometric analysis. The
      crystals belonged to space group P1 and diffracted to 2.1 A resolution. The
      overall structure of SpCynS is very similar to a previously determined structure
      of CynS from Escherichia coli. Density for a ligand bound to the SpCynS active
      site was observed, but could not be unambiguously identified. Additionally,
      glycerol molecules bound at the entry to the active site of the enzyme indicate
      conserved residues that might be important for the trafficking of substrates and
      products. 

PMID- 25849513
TI  - Expression, purification, crystallization and preliminary X-ray diffraction
      analysis of a type II NADH:quinone oxidoreductase from the human pathogen
      Staphylococcus aureus.
AB  - In recent years, type II NADH dehydrogenases (NDH-IIs) have emerged as potential
      drug targets for a wide range of human disease causative agents. In this work,
      the NDH-II enzyme from the Gram-positive human pathogen Staphylococcus aureus was
      recombinantly expressed in Escherichia coli, purified, crystallized and a
      crystallographic data set was collected at a wavelength of 0.873 A. The crystals
      belonged to the orthorhombic space group P212121, with unit-cell parameters a =
      81.8, b = 86.0, c = 269.9 A, contained four monomers per asymmetric unit and
      diffracted to a resolution of 3.32 A. A molecular-replacement solution was
      obtained and model building and refinement are currently under way. 

PMID- 25849514
TI  - Tobacco use and suicide attempt: longitudinal analysis with retrospective
      reports.
AB  - BACKGROUND: Suicide has been associated with smoking/tobacco use but its
      association of and change in smoking/tobacco use status with suicide attempt (SA)
      is not well established. METHODS: We investigated whether persistent, former
      tobacco use, initiation, quitting tobacco use, relapse to tobacco use, and DSM-IV
      nicotine dependence predict independently SA using Wave 1 and 2 data of the
      National Epidemiologic Survey of Alcohol and Related Conditions. Data from 34,653
      US adults interviewed at Wave 1 (2001-02) and Wave 2 (2004-05) were analyzed. The
      main outcome measure was SA between Wave 1 and Wave 2 as reported at Wave 2.
      RESULTS: Among the 1,673 respondents reporting lifetime SA at Wave 2, 328
      individuals reported SA between Wave 1 and Wave 2. Current and former tobacco use
      at Wave 1 predicted Wave 2 SA independently of socio-demographic characteristics,
      psychiatric history, and prior SA (Adjusted Odds Ratio (AOR): 1.49; 95% CI: 1.13
      1.95, AOR: 1.31; 95% CI:1.01-1.69, respectively versus never tobacco users). The
      strongest association with SA was observed among former tobacco users who
      relapsed after Wave 1 (AOR: 4.66; 95% CI: 3.49-6.24) and among tobacco use
      initiators after Wave 1 (AOR: 3.16; 95% CI: 2.23-4.49). Persistent tobacco use
      (current tobacco use at both Wave 1 and Wave 2) also had an increased risk of SA
      (AOR: 1.89; 95% CI: 1.47-2.42). However, former tobacco users in both Waves 1 and
      2 did not show a significantly elevated risk for SA in Wave 2 (AOR:1.09, 95% CI:
      0.78-1.52) suggesting that the risk resided mainly in Wave 1 former tobacco users
      who relapsed to tobacco use by Wave 2. DSM-IV nicotine dependence did not predict
      SA at Wave 2. CONCLUSION: In a representative sample of US adults, relapse,
      tobacco use initiation, and persistent tobacco use, which are amenable to
      intervention, were associated with risk of SA.

PMID- 25849515
TI  - Elucidating the foundations of statistical inference with 2 x 2 tables.
AB  - To many, the foundations of statistical inference are cryptic and irrelevant to
      routine statistical practice. The analysis of 2 x 2 contingency tables,
      omnipresent in the scientific literature, is a case in point. Fisher's exact test
      is routinely used even though it has been fraught with controversy for over 70
      years. The problem, not widely acknowledged, is that several different p-values
      can be associated with a single table, making scientific inference inconsistent.
      The root cause of this controversy lies in the table's origins and the manner in
      which nuisance parameters are eliminated. However, fundamental statistical
      principles (e.g., sufficiency, ancillarity, conditionality, and likelihood) can
      shed light on the controversy and guide our approach in using this test. In this
      paper, we use these fundamental principles to show how much information is lost
      when the tables origins are ignored and when various approaches are used to
      eliminate unknown nuisance parameters. We present novel likelihood contours to
      aid in the visualization of information loss and show that the information loss
      is often virtually non-existent. We find that problems arising from the
      discreteness of the sample space are exacerbated by p-value-based inference.
      Accordingly, methods that are less sensitive to this discreteness - likelihood
      ratios, posterior probabilities and mid-p-values - lead to more consistent
      inferences. 

PMID- 25849516
TI  - The quality of sputum smear microscopy in public-private mix directly observed
      treatment laboratories in West Amhara region, Ethiopia.
AB  - Ethiopia adopted Public-Private Mix Directly Observed Treatment Short Course
      Chemotherapy (PPM-DOTS) strategy for tuberculosis (TB) control program. Quality
      of sputum smear microscopy has paramount importance for tuberculosis control
      program in resource-poor countries like Ethiopia. A cross-sectional study was
      conducted to assess the quality of sputum smear microscopy in 37 Public-Private
      Mix laboratories in West Amhara, Ethiopia. The three external quality assessment
      methods (onsite evaluation, panel testing and blind rechecking) were employed.
      Onsite assessment revealed that 67.6% of PPM-DOTS laboratories were below the
      standard physical space (5 X 6) m2. The average monthly workload per laboratory
      technician was 19.5 (SD+/-2.9) slides with 12.8% positivity rate. The quality of
      Acid Fast Bacilli (AFB) staining reagents was sub-standard. The overall agreement
      for blind rechecking of 1,123 AFB slides was 99.4% (Kappa = 0.97). Reading of 370
      AFB panel slides showed 3.5% false reading (Kappa = 0.92). Moreover, the
      consistency of reading scanty bacilli slides was lower (93%) compared to 1+, 2+
      and 3+ bacilli. Based on blind rechecking and panel testing results, PPM-DOTS
      site laboratories showed good agreement with the reference laboratory. Physical
      space and qualities of AFB reagents would be areas of intervention to sustain the
      quality of sputum smear microscopy. Therefore, regular external quality
      assessment and provision of basic laboratory supplies for TB diagnosis would be
      the way forward to improve the quality of sputum smear microscopy services in PPM
      DOTS laboratories. 

PMID- 25849517
TI  - [Inadequate medical records system--a health risk].

PMID- 25849519
TI  - [Not Available].

PMID- 25849518
TI  - [Transparent teamwork necessary for safe obstetric care. Territorial thinking and
      low competence resulted in healthcare scandal in the UK].

PMID- 25849521
TI  - Preoperative Prognostic Factors and Predictive Score in Patients Operated On for
      Combined Cataract and Idiopathic Epiretinal Membrane.
AB  - PURPOSE: To report preoperative prognostic factors associated with visual acuity
      recovery 1 year after combined cataract and idiopathic epiretinal membrane (ERM)
      surgery and to introduce a predictive score. DESIGN: Interventional case series
      and estimation of a predictive score. METHODS: One hundred forty-two patients (1
      eye per patient) operated on for combined cataract and idiopathic ERM in the
      University Hospital of Dijon were followed for 12 months. Preoperative clinical
      features and spectral-domain optical coherence tomography (OCT) parameters were
      compared between eyes that recovered >=20/20 final best-corrected visual acuity
      (BCVA) and those with <20/20 final BCVA. Multivariate analysis and predictive
      score were provided. RESULTS: At 12 months, 60 eyes (42%) recovered >=20/20 BCVA
      and 82 (58%) had lower visual results. Logistic regression analysis showed that
      final BCVA was associated with age (P = .040), duration of symptoms (P = .025),
      initial BCVA (P = .002), and inner and outer segment (IS/OS) junction disruption
      on spectral-domain OCT (P = .010). The preoperative 10-point predictive score
      including these parameters reached 82% sensitivity and 66% specificity. With a
      score >5, patients had a >=56% chance of recovering 20/20 final BCVA instead of
      <=27% when the score was <=5. CONCLUSIONS: Age, duration of symptoms, and initial
      BCVA appear to be reliable prognostic factors in patients undergoing combined
      cataract and idiopathic ERM surgery. Combining these factors with analysis of the
      IS/OS junction provides a predictive score to estimate individual chances of good
      visual outcome.

PMID- 25849520
TI  - Quantitative Trait Locus Analysis of SIX1-SIX6 With Retinal Nerve Fiber Layer
      Thickness in Individuals of European Descent.
AB  - PURPOSE: To perform a quantitative trait locus (QTL) analysis and evaluate
      whether a locus between SIX1 and SIX6 is associated with retinal nerve fiber
      layer (RNFL) thickness in individuals of European descent. DESIGN: Observational,
      multicenter, cross-sectional study. METHODS: A total of 231 participants were
      recruited from the Diagnostic Innovations in Glaucoma Study and the African
      Descent and Glaucoma Evaluation Study. Association of rs10483727 in SIX1-SIX6
      with global and sectoral RNFL thickness was performed. Quantitative trait
      analysis with the additive model of inheritance was analyzed using linear
      regression. Trend analysis was performed to evaluate the mean global and sectoral
      RNFL thickness with 3 genotypes of interest (T/T, C/T, C/C). All models were
      adjusted for age and sex. RESULTS: Direction of association between T allele and
      RNFL thickness was consistent in the global and different sectoral RNFL regions.
      Each copy of the T risk allele in rs10483727 was associated with -0.16 MUm
      thinner global RNFL thickness (beta = -0.16, 95% confidence interval: -0.28 to 
      0.03; P = .01). Similar patterns were found for the sectoral regions, including
      inferior (P = .03), inferior-nasal (P = .017), superior-nasal (P = .0025),
      superior (P = .002) and superior-temporal (P = .008). The greatest differences
      were observed in the superior and inferior quadrants, supporting clinical
      observations for RNFL thinning in glaucoma. Thinner global RNFL was found in
      subjects with T/T genotypes compared to subjects with C/T and C/C genotypes (P =
      .044). CONCLUSIONS: Each copy of the T risk allele has an additive effect and was
      associated with thinner global and sectoral RNFL. Findings from this QTL analysis
      further support a genetic contribution to glaucoma pathophysiology.

PMID- 25849522
TI  - Spectrum of Retinal Vascular Diseases Associated With Paracentral Acute Middle
      Maculopathy.
AB  - PURPOSE: To evaluate the spectrum of retinal diseases that can demonstrate
      paracentral acute middle maculopathy and isolated ischemia of the intermediate
      and deep capillary plexus. DESIGN: Retrospective, multicenter, observational case
      series. METHODS: This is a retrospective case series review of 9 patients (10
      eyes) from 5 centers with paracentral acute middle maculopathy lesions and
      previously unreported retinal vascular etiologies. Case presentations and
      multimodal imaging, including color photographs, near-infrared reflectance,
      fluorescein angiography, spectral-domain optical coherence tomography (SD OCT),
      and orbital color Doppler imaging, are described. Baseline and follow-up findings
      are correlated with clinical presentation, demographics, and systemic
      associations. RESULTS: Five men and 4 women, aged 27-66 years, were included.
      Isolated band-like hyperreflective lesions in the middle retinal layers,
      otherwise known as paracentral acute middle maculopathy, were observed in all
      patients at baseline presentation. Follow-up SD OCT analysis of these paracentral
      acute middle maculopathy lesions demonstrated subsequent thinning of the inner
      nuclear layer. Novel retinal vascular associations leading to retinal
      vasculopathy and paracentral acute middle maculopathy include eye compression
      injury causing global ocular ischemia, sickle cell crisis, Purtscher's
      retinopathy, inflammatory occlusive retinal vasculitis, post-H1N1 vaccine,
      hypertensive retinopathy, migraine disorder, and post-upper respiratory
      infection. CONCLUSION: Paracentral acute middle maculopathy lesions may develop
      in a wide spectrum of retinal vascular diseases. They are best identified with SD
      OCT analysis and may represent ischemia of the intermediate and deep capillary
      plexus. These lesions typically result in permanent thinning of the inner nuclear
      layer and are critical to identify in order to determine the cause of unexplained
      vision loss.

PMID- 25849524
TI  - Explaining the appeal for immigrant men who have sex with men of a community
      based rapid HIV-testing site in Montreal (Actuel sur Rue).
AB  - Immigrant men who have sex with men (MSM) are vulnerable to HIV. In the last
      decade, several rapid HIV-testing facilities targeting MSM have been established
      around the world and seem popular among immigrants. This study analyzes factors
      contributing to immigrant MSM's use of Actuel sur Rue (AsR), a community-based
      rapid HIV-testing site in Montreal's gay village, where 31% of clients are
      immigrants. From October 2013 to January 2014, AsR staff compiled a list of new
      clients born outside of Canada. With their consent, 40 immigrant MSM were reached
      among these new clients for a 15-minute phone survey entailing open-ended and
      multiple-choice questions. The survey sought immigrant MSM's reasons for visiting
      AsR; satisfaction with service and staff; and open comments. An inductive
      thematic analysis was conducted with the qualitative data, and descriptive
      statistics were produced with the quantitative data. The qualitative findings
      indicate that the main reasons for seeking an HIV test were a recent risk,
      routine testing, or being in a new relationship. Clients chose AsR mainly because
      it is easily accessible, service is fast or they heard about it from a friend.
      The quantitative findings indicate that rates of satisfaction were high (over 90%
      were satisfied about all aspects except for openings hours) and more than 80%
      felt comfortable while receiving services at AsR. Nevertheless, this study's
      findings have implications for improving services. They stress the importance of
      offering rapid yet comprehensive service and of taking into account immigrant
      MSM's concerns for confidentiality. 

PMID- 25849523
TI  - The effectiveness of lifestyle triple P in the Netherlands: a randomized
      controlled trial.
AB  - INTRODUCTION: Lifestyle Triple P is a general parenting intervention which
      focuses on preventing further excessive weight gain in overweight and obese
      children. The objective of the current study was to assess the effectiveness of
      the Lifestyle Triple P intervention in the Netherlands. METHOD: We used a
      parallel randomized controlled design to test the effectiveness of the
      intervention. In total, 86 child-parent triads (children 4-8 years old,
      overweight or obese) were recruited and randomly assigned (allocation ratio 1:1)
      to the Lifestyle Triple P intervention or the control condition. Parents in the
      intervention condition received a 14-week intervention consisting of ten 90
      minute group sessions and four individual telephone sessions. Primary outcome
      measure was the children's body composition (BMI z-scores, waist circumference
      and skinfolds). The research assistant who performed the measurements was blinded
      for group assignment. Secondary outcome measures were the children's dietary
      behavior and physical activity level, parenting practices, parental feeding
      style, parenting style, and parental self-efficacy. Outcome measures were
      assessed at baseline and 4 months (short-term) and 12 months (long-term) after
      baseline. Multilevel multiple regression analyses were conducted to determine the
      effect of the intervention on primary and secondary outcome measures. RESULTS: No
      intervention effects were found on children's body composition. Analyses of
      secondary outcomes showed positive short-term intervention effects on children's
      soft-drink consumption and parental responsibility regarding physical activity,
      encouragement to eat, psychological control, and efficacy and satisfaction with
      parenting. Longer-term intervention effects were found on parent's report of
      children's time spent on sedentary behavior and playing outside, parental
      monitoring food intake, and responsibility regarding nutrition. CONCLUSION:
      Although the Lifestyle Triple P intervention showed positive effects on some
      parent reported child behaviors and parenting measures, no effects were visible
      on children's body composition or objectively measured physical activity. Several
      adjustments of the intervention content are recommended, for example including a
      booster session. TRIAL REGISTRATION: Nederlands Trial Register NTR 2555.

PMID- 25849525
TI  - Activation of cannabinoid CB2 receptors reduces hyperalgesia in an experimental
      autoimmune encephalomyelitis mouse model of multiple sclerosis.
AB  - Clinical trials investigating the analgesic efficacy of cannabinoids in multiple
      sclerosis have yielded mixed results, possibly due to psychotropic side effects
      mediated by cannabinoid CB1 receptors. We hypothesized that, a CB2-specific
      agonist (JWH-133) would decrease hyperalgesia in an experimental autoimmune
      encephalomyelitis mouse model of multiple sclerosis. Four weeks after induction
      of experimental autoimmune encephalomyelitis, we found that intrathecal
      administration of JWH-133 (10-100MUg) dose-dependently reduced both mechanical
      and cold hypersensitivity without producing signs of sedation or ataxia. The anti
      hyperalgesic effects of JWH-133 could be dose-dependently prevented by
      intrathecal co-administration of the CB2 antagonist, AM-630 (1-3MUg). Our results
      suggest that JWH-133 acts at CB2 receptors, most likely within the dorsal horn of
      the spinal cord, to suppress the hypersensitivity associated with experimental
      autoimmune encephalomyelitis. These are the first pre-clinical studies to
      directly promote CB2 as a promising target for the treatment of central pain in
      an animal model of multiple sclerosis. 

PMID- 25849526
TI  - A novel brain-derived neurotrophic factor-modulating peptide attenuates Abeta1-42
      induced neurotoxicity in vitro.
AB  - Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family,
      which plays important roles in learning and memory formation and in protecting
      neurons from diverse neurotoxic insults, such as amyloid-beta (Abeta). Since BDNF
      expression is decreased in patients with Alzheimer's disease, various strategies
      have attempted to increase BDNF levels. In a previous study, we screened and
      identified a novel BDNF-modulating peptide (consisting of methionine-valine
      glycine, named Neuropep-1) by a positional scanning-synthetic peptide
      combinatorial library (PS-SPCL). Neuropep-1 exhibited neuroprotective effects
      against in vitro and in vivo Alzheimer's disease models. Based on the previous PS
      SPCL data, we modified the amino acid sequence of Neuropep-1 in this study to
      identify a more potent novel BDNF-modulating peptide. By replacing the valine in
      the second position with aspartic acid, the resulting Neuropep-4 was found to be
      highly effective in inducing BDNF expression even at concentrations of 1pM in the
      SH-SY5Y cell line and rat primary cortical neurons. In addition, among the tested
      peptides, Neuropep-4 provided neurons with the strongest protection against
      oligomeric and/or fibrillar Abeta1-42-induced cell death through BDNF
      upregulation. These results suggest the potential of Neuropep-4 as a therapeutic
      candidate for treating neurodegenerative diseases, such as AD. 

PMID- 25849527
TI  - Neurological soft signs in primary headache patients.
AB  - Neurological soft signs (NSS) are semeiotic anomalies not assessed by the
      standard neurological examination, primarily developed in psychiatric settings
      and recently proposed as potential markers of minor brain circuit alterations,
      especially the cerebellar-thalamic-prefrontal network. Primary headache patients
      present with normal neurological examination and frequent psychiatric
      comorbidity. Aim of this exploratory study consisted in assessing NSS in 20
      episodic frequent migraine (MH) and in 10 tension-type headache (ETTH)
      outpatients compared to 30 matched healthy controls. NSS were assessed by the
      Heidelberg scale; clinical characteristics and brain MRI were additionally
      obtained in all patients. NSS were increased by ~70 and ~90% in ETTH and MH,
      respectively, with respect to controls (p<0.001) and the difference remained
      significant even after controlling for age and education. Headache type and
      characteristics did not influence NSS presentation, while headache patients with
      white matter hyperintensities (WMH) at brain MRI had higher NSS scores compared
      both to normal controls and patients without WMH. NSS identify a subset of
      primary headache patients sharing the same comorbidities or minimal brain
      anomalies, suggesting that tailored prophylactic options might apply. 

PMID- 25849528
TI  - Coarse topographic organization of pheromone-sensitive afferents from different
      antennal surfaces in the American cockroach.
AB  - In contrast to visual, auditory, taste, and mechanosensory neuropils, in which
      sensory afferents are topographically organized on the basis of their peripheral
      soma locations, axons of cognate sensory neurons from different locations of the
      olfactory sense organ converge onto a small spherical neuropil (glomerulus) in
      the first-order olfactory center. In the cockroach Periplaneta americana, sex
      pheromone-sensitive afferents with somata in the antero-dorsal and postero
      ventral surfaces of a long whip-like antenna are biased toward the anterior and
      posterior regions of a macroglomerulus, respectively. In each region, afferents
      with somata in the more proximal antenna project to more proximal region,
      relative to the axonal entry points. However, precise topography of afferents in
      the macroglomerulus has remained unknown. Using single and multiple neuronal
      stainings, we showed that afferents arising from anterior, dorsal, ventral and
      posterior surfaces of the proximal regions of an antenna were biased
      progressively from the anterior to posterior region of the macroglomerulus,
      reflecting chiasmatic axonal re-arrangements that occur immediately before
      entering the antennal lobe. Morphologies of individual afferents originating from
      the proximal antenna matched results of mass neuronal stainings, but their three
      dimensional origins in the antenna were hardly predictable on the basis of the
      projection patterns. Such projection biases made by neuronal populations differ
      from strict somatotopic projections of antennal mechanosensory neurons in the
      same species, suggesting a unique sensory mechanism to process information about
      odor location and direction on a single antenna. 

PMID- 25849529
TI  - Effects of 1,8-cineole on Na(+) currents of dissociated superior cervical ganglia
      neurons.
AB  - 1,8-Cineole is a terpenoid present in many essential oil of plants with several
      pharmacological and biological effects, including antinociceptive, smooth muscle
      relaxant and ion channel activation. Also, 1,8-cineole blocked action potentials,
      reducing excitability of peripheral neurons. The objective of this work was to
      investigate effects of 1,8-cineole on Na(+) currents (INa(+)) in dissociated
      superior cervical ganglion neurons (SCG). Wistar rats of both sexes were used (10
      12 weeks old, 200-300g). SCG's were dissected and neurons were enzymatically
      treated. To study 1,8-cineole effect on INa(+), the patch-clamp technique in
      whole-cell mode was employed. 1,8-Cineole (6.0mM) partially blocked INa(+) in SCG
      neurons. The effect stabilized within ~150s and there was a partial recovery of
      INa(+) after washout. Current density was reduced from -105.8 to -83.7pA/pF,
      corresponding to a decrease to ~20% of control. 1,8-Cineole also reduced the time
      to-peak of INa(+) activation and the amplitude and decay time constants of INa(+)
      inactivation. Current-voltage plots revealed that 1,8-cineole left-shifted the
      V1/2 of both activation and inactivation curves by ~10 and ~20mV, respectively.
      In conclusion, we demonstrate that 1,8-cineole directly affects Na(+) channels of
      the SCG by modifying several gating parameters that are likely to be the major
      cause of excitability blockade. 

PMID- 25849530
TI  - Continuous control of the nonlinearity phase for harmonic generations.
AB  - The capability of locally engineering the nonlinear optical properties of media
      is crucial in nonlinear optics. Although poling is the most widely employed
      technique for achieving locally controlled nonlinearity, it leads only to a
      binary nonlinear state, which is equivalent to a discrete phase change of pi in
      the nonlinear polarizability. Here, inspired by the concept of spin-rotation
      coupling, we experimentally demonstrate nonlinear metasurfaces with homogeneous
      linear optical properties but spatially varying effective nonlinear
      polarizability with continuously controllable phase. The continuous phase control
      over the local nonlinearity is demonstrated for second and third harmonic
      generation by using nonlinear metasurfaces consisting of nanoantennas of C3 and
      C4 rotational symmetries, respectively. The continuous phase engineering of the
      effective nonlinear polarizability enables complete control over the propagation
      of harmonic generation signals. Therefore, this method seamlessly combines the
      generation and manipulation of harmonic waves, paving the way for highly compact
      nonlinear nanophotonic devices. 

PMID- 25849531
TI  - Enhancement of the chemical stability in confined delta-Bi2O3.
AB  - Bismuth-oxide-based materials are the building blocks for modern ferroelectrics,
      multiferroics, gas sensors, light photocatalysts and fuel cells. Although the
      cubic fluorite delta-phase of bismuth oxide (delta-Bi2O3) exhibits the highest
      conductivity of known solid-state oxygen ion conductors, its instability prevents
      use at low temperature. Here we demonstrate the possibility of stabilizing delta
      Bi2O3 using highly coherent interfaces of alternating layers of Er2O3-stabilized
      delta-Bi2O3 and Gd2O3-doped CeO2. Remarkably, an exceptionally high chemical
      stability in reducing conditions and redox cycles at high temperature, usually
      unattainable for Bi2O3-based materials, is achieved. Even more interestingly, at
      low oxygen partial pressure the layered material shows anomalous high
      conductivity, equal or superior to pure delta-Bi2O3 in air. This suggests a
      strategy to design and stabilize new materials that are comprised of
      intrinsically unstable but high-performing component materials. 

PMID- 25849532
TI  - Lead halide perovskite nanowire lasers with low lasing thresholds and high
      quality factors.
AB  - The remarkable performance of lead halide perovskites in solar cells can be
      attributed to the long carrier lifetimes and low non-radiative recombination
      rates, the same physical properties that are ideal for semiconductor lasers.
      Here, we show room-temperature and wavelength-tunable lasing from single-crystal
      lead halide perovskite nanowires with very low lasing thresholds (220 nJ cm(-2))
      and high quality factors (Q ~ 3,600). The lasing threshold corresponds to a
      charge carrier density as low as 1.5 * 10(16) cm(-3). Kinetic analysis based on
      time-resolved fluorescence reveals little charge carrier trapping in these single
      crystal nanowires and gives estimated lasing quantum yields approaching 100%.
      Such lasing performance, coupled with the facile solution growth of single
      crystal nanowires and the broad stoichiometry-dependent tunability of emission
      colour, makes lead halide perovskites ideal materials for the development of
      nanophotonics, in parallel with the rapid development in photovoltaics from the
      same materials. 

PMID- 25849533
TI  - Aberrant fat metabolism in Caenorhabditis elegans mutants with defects in the
      defecation motor program.
AB  - The molecular mechanisms by which dietary fatty acids are absorbed by the
      intestine, and the way in which the process is regulated are poorly understood.
      In a genetic screen for mutations affecting fat accumulation in the intestine of
      Caenorhabditis elegans, nematode worms, we have isolated mutations in the aex-5
      gene, which encodes a Kex2/subtilisin-family, Ca2+-sensitive proprotein
      convertase known to be required for maturation of certain neuropeptides, and for
      a discrete step in an ultradian rhythmic phenomenon called the defecation motor
      program. We demonstrate that aex-5 mutants have markedly lower steady-state
      levels of fat in the intestine, and that this defect is associated with a
      significant reduction in the rate at which labeled fatty acid derivatives are
      taken up from the intestinal lumen. Other mutations affecting the defecation
      motor program also affect steady-state levels of triglycerides, suggesting that
      the program is required per se for the proper accumulation of neutral lipids. Our
      results suggest that an important function of the defecation motor program in C.
      elegans is to promote the uptake of an important class of dietary nutrients. They
      also imply that modulation of the program might be one way in which worms adjust
      nutrient uptake in response to altered metabolic status. 

PMID- 25849534
TI  - Predictability of road traffic and congestion in urban areas.
AB  - Mitigating traffic congestion on urban roads, with paramount importance in urban
      development and reduction of energy consumption and air pollution, depends on our
      ability to foresee road usage and traffic conditions pertaining to the collective
      behavior of drivers, raising a significant question: to what degree is road
      traffic predictable in urban areas? Here we rely on the precise records of daily
      vehicle mobility based on GPS positioning device installed in taxis to uncover
      the potential daily predictability of urban traffic patterns. Using the mapping
      from the degree of congestion on roads into a time series of symbols and
      measuring its entropy, we find a relatively high daily predictability of traffic
      conditions despite the absence of any priori knowledge of drivers' origins and
      destinations and quite different travel patterns between weekdays and weekends.
      Moreover, we find a counterintuitive dependence of the predictability on travel
      speed: the road segment associated with intermediate average travel speed is most
      difficult to be predicted. We also explore the possibility of recovering the
      traffic condition of an inaccessible segment from its adjacent segments with
      respect to limited observability. The highly predictable traffic patterns in
      spite of the heterogeneity of drivers' behaviors and the variability of their
      origins and destinations enables development of accurate predictive models for
      eventually devising practical strategies to mitigate urban road congestion. 

PMID- 25849535
TI  - Tonsillectomy and the risk for deep neck infection-a nationwide cohort study.
AB  - BACKGROUND: Although the tonsils contribute to first line immunity against
      foreign pathogens in the upper aero-digestive tract, the association of
      tonsillectomy with the risk of deep neck infection remains unclear. The aim of
      this study was to assess the incidence rate and risk of deep neck infection among
      patients who had undergone a tonsillectomy. METHODS: This retrospective cohort
      study evaluated all patients who had undergone tonsillectomy between 2001 and
      2009 as identified from the Taiwan National Health Insurance Research Database.
      For each post-tonsillectomy patient, 10 age-, sex-, and index date-matched
      controls without a history of tonsillectomy were randomly selected. Cox
      Proportional hazard model and propensity score model were performed to evaluate
      the association between tonsillectomy and deep neck infection after adjusting for
      demographic and clinical data. RESULTS: There were 34 (71.6 cases per 100,000
      person-years) and 174 (36.6 cases per 100,000 person-years) patients that
      developed deep neck infection in the tonsillectomized and comparison cohorts,
      respectively. After adjusting for covariates, patients who had undergone a
      tonsillectomy had a 1.71-fold greater risk of deep neck infection by both Cox
      proportional hazard model (95% confidence interval, 1.13-2.59) and propensity
      score model (95% confidence interval, 1.10-2.66). This association was not
      altered regardless of the indication for tonsillectomy (i.e. chronic/recurrent
      tonsillitis or sleep apnea/hypertrophy of tonsil) (p = 0.9797). CONCLUSIONS:
      Based on our review of a nationwide cohort study we identified that the risk of
      deep neck infection is significantly increased among patients who have undergone
      a tonsillectomy. Additional research is needed to explore the possible mechanisms
      behind these findings.

PMID- 25849536
TI  - A five-year prospective study of diabetic retinopathy progression in chinese type
      2 diabetes patients with "well-controlled" blood glucose.
AB  - PURPOSE: To determine the progression rate and risk factors for diabetic
      retinopathy (DR) in Chinese type 2 diabetic patients who have reached the target
      hemoglobin A1c (HbA1c) level recommended by the American Diabetes Association.
      METHODS: This was a 5-year community-based prospective study. The study
      population consisted of patients with type 2 diabetes with HbA1c less than 7.0%.
      Demographic information, systemic examination results and ophthalmological test
      results for each participant were collected. The outcome of this study was the
      progression of DR, which was defined as an increase in DR grade in one or both
      eyes at the final visit in comparison to the baseline status. The association
      between each potential risk factor and DR progression was studied. RESULTS: A
      total of 453 patients with HbA1c less than 7.0% were included in the study group.
      In 146 patients (32.22%), DR developed or progressed during the five-year follow
      up. Baseline HbA1c level was the only independent risk factor for DR progression
      (p<0.01, OR = 2.84, 95%CI: 2.11~3.82). The logistic regression function suggested
      that the possibility of DR progression increased fastest when baseline HbA1c
      increased from 5.2% to 6.4%. The 5-year DR progression rate in patients with
      baseline HbA1c less than 5.2%, between 5.2% and 6.4%, and over 6.4% were 19.62%,
      24.41%, and 76.83%, respectively. CONCLUSIONS: To slow the progression of DR in
      Chinese patients with type 2 diabetes, more intensive glucose control is
      recommended.

PMID- 25849537
TI  - Rye affects bacterial translocation, intestinal viscosity, microbiota composition
      and bone mineralization in Turkey poults.
AB  - Previously, we have reported that rye significantly increased both viscosity and
      Clostridium perfringens proliferation when compared with corn in an in vitro
      digestive model. Two independent trials were conducted to evaluate the effect of
      rye as a source of energy on bacterial translocation, intestinal viscosity, gut
      microbiota composition, and bone mineralization, when compared with corn in
      turkey poults. In each experiment, day-of-hatch, turkey poults were randomly
      assigned to either a corn or a rye diet (n = 0 /group). At 10 d of age, in both
      experiments, 12 birds/group were given an oral gavage dose of fluorescein
      isothiocyanate dextran (FITC-d). After 2.5 h of oral gavage, blood and liver
      samples were collected to evaluate the passage of FITC-d and bacterial
      translocation (BT) respectively. Duodenum, ileum and cecum gut sections were
      collected to evaluate intestinal viscosity and to enumerate gut microbiota.
      Tibias were collected for observation of bone parameters. Broilers fed with a rye
      diet showed increased (p<0.05) intestinal viscosity, BT, and serum FITC-d.
      Bacterial enumeration revealed that turkey poults fed with rye had increased the
      number of total lactic acid bacteria (LAB) in all three sections of the
      gastrointestinal tract evaluated when compared to turkey poults fed with corn.
      Turkey poults fed with rye also had significantly higher coliforms in duodenum
      and ileum but not in the ceca, whereas the total number of anaerobes increased
      only in duodenum. A significant reduction in bone strength and bone
      mineralization was observed in turkey poults fed with rye when compared with corn
      fed turkey poults. In conclusion, rye evoked mucosal damage in turkey poults that
      increased intestinal viscosity, increased leakage through the intestinal tract,
      and altered the microbiota composition and bone mineralization. Studies to
      evaluate dietary inclusion of selected Direct-Fed Microbial (DFM) candidates that
      produce exogenous enzymes in rye fed turkey poults are currently being evaluated.

PMID- 25849538
TI  - Activation of glycoprotein VI (GPVI) and C-type lectin-like receptor-2 (CLEC-2)
      underlies platelet activation by diesel exhaust particles and other
      charged/hydrophobic ligands.
AB  - Platelets are activated by a range of stimuli that share little or no resemblance
      in structure to each other or to recognized ligands, including diesel exhaust
      particles (DEP), small peptides [4N1-1, Champs (computed helical anti-membrane
      proteins), LSARLAF (Leu-Ser-Ala-Arg-Leu-Ala-Phe)], proteins (histones) and large
      polysaccharides (fucoidan, dextran sulfate). This miscellaneous group stimulate
      aggregation of human and mouse platelets through the glycoprotein VI (GPVI)-FcR
      gamma-chain complex and/or C-type lectin-like receptor-2 (CLEC-2) as shown using
      platelets from mice deficient in either or both of these receptors. In addition,
      all of these ligands stimulate tyrosine phosphorylation in GPVI/CLEC-2-double
      deficient platelets, indicating that they bind to additional surface receptors,
      although only in the case of dextran sulfate does this lead to activation. DEP,
      fucoidan and dextran sulfate, but not the other agonists, activate GPVI and CLEC
      2 in transfected cell lines as shown using a sensitive reporter assay confirming
      a direct interaction with the two receptors. We conclude that this miscellaneous
      group of ligands bind to multiple proteins on the cell surface including GPVI
      and/or CLEC-2, inducing activation. These results have pathophysiological
      significance in a variety of conditions that involve exposure to activating
      charged/hydrophobic agents. 

PMID- 25849539
TI  - Exposure to airborne particles and volatile organic compounds from polyurethane
      molding, spray painting, lacquering, and gluing in a workshop.
AB  - Due to the health risk related to occupational air pollution exposure, we
      assessed concentrations and identified sources of particles and volatile organic
      compounds (VOCs) in a handcraft workshop producing fishing lures. The work
      processes in the site included polyurethane molding, spray painting, lacquering,
      and gluing. We measured total VOC (TVOC) concentrations and particle size
      distributions at three locations representing the various phases of the
      manufacturing and assembly process. The mean working-hour TVOC concentrations in
      three locations studied were 41, 37, and 24 ppm according to photo-ionization
      detector measurements. The mean working-hour particle number concentration varied
      between locations from 3000 to 36,000 cm-3. Analysis of temporal and spatial
      variations of TVOC concentrations revealed that there were at least four
      substantial VOC sources: spray gluing, mold-release agent spraying, continuous
      evaporation from various lacquer and paint containers, and either spray painting
      or lacquering (probably both). The mold-release agent spray was indirectly also a
      major source of ultrafine particles. The workers' exposure can be reduced by
      improving the local exhaust ventilation at the known sources and by increasing
      the ventilation rate in the area with the continuous source. 

PMID- 25849540
TI  - Cross-sectional associations of depressive symptom severity and functioning with
      health service use by older people in low-and-middle income countries.
AB  - BACKGROUND: Comprehensive understanding of the determinants of health service use
      (HSU) by older people with depression is essential for health service planning
      for an ageing global population. This study aimed to determine the extent to
      which depressive symptom severity and functioning are associated with HSU by
      older people with depression in low and middle income countries (LMICs). METHODS:
      A cross-sectional analysis of the 10/66 Dementia Research Group population-based
      surveys dataset. Participants (n = 4590) were those aged 65 or older, in the
      clinical range for depressive symptoms (defined as scoring four or more on the
      EURO-D), living in 13 urban and/or rural catchment areas in nine LMICs.
      Associations were calculated using Poisson regression and random-effects meta
      analysis. RESULTS: After adjustment for confounding variables, (EURO-D)
      depressive symptom severity was significantly associated with "any community HSU"
      (Pooled Prevalence Ratios = 1.02; 95% CI = 1.01-1.03) but not hospital admission.
      Conversely, after adjustment, (WHODAS-II) functioning was significantly
      associated with hospital admission (Pooled PR = 1.14; 95% CI = 1.02-1.26) but not
      "any community HSU". CONCLUSIONS: Depressive symptom severity does not explain a
      large proportion of the variance in HSU by older people with depression in LMICs.
      The association of functioning with this HSU is worthy of further investigation.
      In LMICs, variables related to accessibility may be more important correlates of
      HSU than variables directly related to health problems.

PMID- 25849541
TI  - Mouse mammary stem cells express prognostic markers for triple-negative breast
      cancer.
AB  - INTRODUCTION: Triple-negative breast cancer (TNBC) is a heterogeneous group of
      tumours in which chemotherapy, the current mainstay of systemic treatment, is
      often initially beneficial but with a high risk of relapse and metastasis. There
      is currently no means of predicting which TNBC will relapse. We tested the
      hypothesis that the biological properties of normal stem cells are re-activated
      in tumour metastasis and that, therefore, the activation of normal mammary stem
      cell-associated gene sets in primary TNBC would be highly prognostic for relapse
      and metastasis. METHODS: Mammary basal stem and myoepithelial cells were isolated
      by flow cytometry and tested in low-dose transplant assays. Gene expression
      microarrays were used to establish expression profiles of the stem and
      myoepithelial populations; these were compared to each other and to our
      previously established mammary epithelial gene expression profiles. Stem cell
      genes were classified by Gene Ontology (GO) analysis and the expression of a
      subset analysed in the stem cell population at single cell resolution. Activation
      of stem cell genes was interrogated across different breast cancer cohorts and
      within specific subtypes and tested for clinical prognostic power. RESULTS: A set
      of 323 genes was identified that was expressed significantly more highly in the
      purified basal stem cells compared to all other cells of the mammary epithelium.
      A total of 109 out of 323 genes had been associated with stem cell features in at
      least one other study in addition to our own, providing further support for their
      involvement in the biology of this cell type. GO analysis demonstrated an
      enrichment of these genes for an association with cell migration, cytoskeletal
      regulation and tissue morphogenesis, consistent with a role in invasion and
      metastasis. Single cell resolution analysis showed that individual cells co
      expressed both epithelial- and mesenchymal-associated genes/proteins. Most
      strikingly, we demonstrated that strong activity of this stem cell gene set in
      TNBCs identified those tumours most likely to rapidly progress to metastasis.
      CONCLUSIONS: Our findings support the hypothesis that the biological properties
      of normal stem cells are drivers of metastasis and that these properties can be
      used to stratify patients with a highly heterogeneous disease such as TNBC.

PMID- 25849542
TI  - The short-term cost-effectiveness of once-daily liraglutide versus once-weekly
      exenatide for the treatment of type 2 diabetes mellitus in the United States.
AB  - BACKGROUND: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease with
      substantial morbidity, mortality, and economic impacts. Glucagon-like peptide-1
      (GLP-1) receptor agonists, such as once-daily (QD) liraglutide and once-weekly
      (QW) exenatide, are FDA-approved treatment for T2DM. Head-to-head trials and meta
      analyses comparing these agents have reported clinically meaningful improvements
      but small differences in glycemic control between both agents. In this study, we
      calculate and compare the cost-effectiveness implications of these alternative
      effectiveness outcomes. METHODS: We developed a decision model to evaluate the
      short-term cost-effectiveness of exenatide QW 2 mg versus liraglutide QD 1.8 mg
      in T2DM patients, with effectiveness measured as reduction in glycated hemoglobin
      (HbA1c). In the base case, the model tracks change in HbA1c and direct medical
      expenditure over a 6-month time horizon. We calculated and compared the cost per
      1% reduction in HbA1c of models populated with clinical data from a head-to-head
      randomized, controlled trial (DURATION-6) and a network meta-analysis.
      Expenditure inputs were derived from wholesale acquisition costs and published
      sources. RESULTS: In the base case, 6-month expenditure for the liraglutide and
      exenatide strategies were $3,509 and $2,618, respectively. Using clinical data
      from DURATION-6 and the network meta-analysis, the liraglutide strategy had an
      incremental cost per 1% reduction in HbA1c of $4,773 and $27,179, respectively.
      The most influential model parameters were drug costs, magnitude of HbA1c
      reduction in patients on treatment for >1 month, and liraglutide gastrointestinal
      adverse event rate. In probabilistic sensitivity analyses (PSA) using DURATION-6
      data, the exenatide strategy was optimal at willingness-to-pay levels below
      $4,800 per 1% reduction in HbA1c. In a PSA using meta-analysis data, the
      exenatide strategy was dominant. CONCLUSIONS: Our modeled results demonstrate
      that the effectiveness and cost-effectiveness of liraglutide QD 1.8 mg relative
      to exenatide QW 2 mg depend largely on the chosen source of the clinical data.

PMID- 25849544
TI  - GATE validation of standard dual energy corrections in small animal SPECT-CT.
AB  - This paper addresses 123I and 125I dual isotope SPECT imaging, which can be
      challenging because of spectrum overlap in the low energy spectrums of these
      isotopes. We first quantify the contribution of low-energy photons from each
      isotope using GATE-based Monte Carlo simulations for the MOBY mouse phantom. We
      then describe and analyze a simple, but effective method that uses the ratio of
      detected low and high energy 123I activity to separate the mixed low energy 123I
      and 125I activities. Performance is compared with correction methods used in
      conventional tissue biodistribution techniques. The results indicate that the
      spectrum overlap effects can be significantly reduced, if not entirely
      eliminated, when attenuation and scatter is either absent or corrected for using
      standard methods. In particular, we show that relative activity levels of the two
      isotopes can be accurately estimated for a wide range of organs and provide
      quantitative validation that standard methods for spectrum overlap correction
      provide reasonable estimates for reasonable corrections in small-animal SPECT/CT
      imaging. 

PMID- 25849543
TI  - Leukocyte-derived IFN-alpha/beta and epithelial IFN-lambda constitute a
      compartmentalized mucosal defense system that restricts enteric virus infections.
AB  - Epithelial cells are a major port of entry for many viruses, but the molecular
      networks which protect barrier surfaces against viral infections are incompletely
      understood. Viral infections induce simultaneous production of type I (IFN
      alpha/beta) and type III (IFN-lambda) interferons. All nucleated cells are
      believed to respond to IFN-alpha/beta, whereas IFN-lambda responses are largely
      confined to epithelial cells. We observed that intestinal epithelial cells,
      unlike hematopoietic cells of this organ, express only very low levels of
      functional IFN-alpha/beta receptors. Accordingly, after oral infection of IFN
      alpha/beta receptor-deficient mice, human reovirus type 3 specifically infected
      cells in the lamina propria but, strikingly, did not productively replicate in
      gut epithelial cells. By contrast, reovirus replicated almost exclusively in gut
      epithelial cells of IFN-lambda receptor-deficient mice, suggesting that the gut
      mucosa is equipped with a compartmentalized IFN system in which epithelial cells
      mainly respond to IFN-lambda that they produce after viral infection, whereas
      other cells of the gut mostly rely on IFN-alpha/beta for antiviral defense. In
      suckling mice with IFN-lambda receptor deficiency, reovirus replicated in the gut
      epithelium and additionally infected epithelial cells lining the bile ducts,
      indicating that infants may use IFN-lambda for the control of virus infections in
      various epithelia-rich tissues. Thus, IFN-lambda should be regarded as an
      autonomous virus defense system of the gut mucosa and other epithelial barriers
      that may have evolved to avoid unnecessarily frequent triggering of the IFN
      alpha/beta system which would induce exacerbated inflammation. 

PMID- 25849545
TI  - Post-PKS tailoring steps of a disaccharide-containing polyene NPP in
      Pseudonocardia autotrophica.
AB  - A novel polyene compound NPP identified in a rare actinomycetes, Pseudonocardia
      autotrophica KCTC9441, was shown to contain an aglycone identical to nystatin but
      to harbor a unique di-sugar moiety, mycosaminyl-(alpha1-4)-N-acetyl-glucosamine,
      which led to higher solubility and reduced hemolytic activity. Although the nppDI
      was proved to be responsible for the transfer of first polyene sugar, mycosamine
      in NPP biosynthesis, the gene responsible for the second sugar extending
      glycosyltransferase (GT) as well as NPP post-PKS tailoring mechanism remained
      unknown. Here, we identified a NPP-specific second sugar extending GT gene named
      nppY, located at the edge of the NPP biosynthetic gene cluster. Targeted nppY
      gene deletion and its complementation proved that nppY is indeed responsible for
      the transfer of second sugar, N-acetyl-glucosamine in NPP biosynthesis. Site
      directed mutagenesis on nppY also revealed several amino acid residues critical
      for NppY GT function. Moreover, a combination of deletions and complementations
      of two GT genes (nppDI and nppY) and one P450 hydroxylase gene (nppL) involved in
      the NPP post-PKS biosynthesis revealed that NPP aglycone is sequentially modified
      by the two different GTs encoded by nppDI and nppY, respectively, followed by the
      nppL-driven regio-specific hydroxylation at the NPP C10 position. These results
      set the stage for the biotechnological application of sugar diversification for
      the biosynthesis of novel polyene compounds in actinomycetes. 

PMID- 25849546
TI  - Detection of convergent genome-wide signals of adaptation to tropical forests in
      humans.
AB  - Tropical forests are believed to be very harsh environments for human life. It is
      unclear whether human beings would have ever subsisted in those environments
      without external resources. It is therefore possible that humans have developed
      recent biological adaptations in response to specific selective pressures to cope
      with this challenge. To understand such biological adaptations we analyzed genome
      wide SNP data under a Bayesian statistics framework, looking for outlier markers
      with an overly large extent of differentiation between populations living in a
      tropical forest, as compared to genetically related populations living outside
      the forest in Africa and the Americas. The most significant positive selection
      signals were found in genes related to lipid metabolism, the immune system, body
      development, and RNA Polymerase III transcription initiation. The results are
      discussed in the light of putative tropical forest selective pressures, namely
      food scarcity, high prevalence of pathogens, difficulty to move, and inefficient
      thermoregulation. Agreement between our results and previous studies on the pygmy
      phenotype, a putative prototype of forest adaptation, were found, suggesting that
      a few genetic regions previously described as associated with short stature may
      be evolving under similar positive selection in Africa and the Americas. In
      general, convergent evolution was less pervasive than local adaptation in one
      single continent, suggesting that Africans and Amerindians may have followed
      different routes to adapt to similar environmental selective pressures. 

PMID- 25849547
TI  - Clustering consumers based on trust, confidence and giving behaviour: data-driven
      model building for charitable involvement in the Australian not-for-profit
      sector.
AB  - Organisations in the Not-for-Profit and charity sector face increasing
      competition to win time, money and efforts from a common donor base.
      Consequently, these organisations need to be more proactive than ever. The
      increased level of communications between individuals and organisations today,
      heightens the need for investigating the drivers of charitable giving and
      understanding the various consumer groups, or donor segments, within a
      population. It is contended that 'trust' is the cornerstone of the not-for-profit
      sector's survival, making it an inevitable topic for research in this context. It
      has become imperative for charities and not-for-profit organisations to adopt for
      profit's research, marketing and targeting strategies. This study provides the
      not-for-profit sector with an easily-interpretable segmentation method based on a
      novel unsupervised clustering technique (MST-kNN) followed by a feature saliency
      method (the CM1 score). A sample of 1,562 respondents from a survey conducted by
      the Australian Charities and Not-for-profits Commission is analysed to reveal
      donor segments. Each cluster's most salient features are identified using the CM1
      score. Furthermore, symbolic regression modelling is employed to find cluster
      specific models to predict 'low' or 'high' involvement in clusters. The MST-kNN
      method found seven clusters. Based on their salient features they were labelled
      as: the 'non-institutionalist charities supporters', the 'resource allocation
      critics', the 'information-seeking financial sceptics', the 'non-questioning
      charity supporters', the 'non-trusting sceptics', the 'charity management
      believers' and the 'institutionalist charity believers'. Each cluster exhibits
      their own characteristics as well as different drivers of 'involvement'. The
      method in this study provides the not-for-profit sector with a guideline for
      clustering, segmenting, understanding and potentially targeting their donor base
      better. If charities and not-for-profit organisations adopt these strategies,
      they will be more successful in today's competitive environment. 

PMID- 25849548
TI  - Deep phylogenetic analysis of haplogroup G1 provides estimates of SNP and STR
      mutation rates on the human Y-chromosome and reveals migrations of Iranic
      speakers.
AB  - Y-chromosomal haplogroup G1 is a minor component of the overall gene pool of
      South-West and Central Asia but reaches up to 80% frequency in some populations
      scattered within this area. We have genotyped the G1-defining marker M285 in 27
      Eurasian populations (n= 5,346), analyzed 367 M285-positive samples using 17 Y
      STRs, and sequenced ~11 Mb of the Y-chromosome in 20 of these samples to an
      average coverage of 67X. This allowed detailed phylogenetic reconstruction. We
      identified five branches, all with high geographical specificity: G1-L1323 in
      Kazakhs, the closely related G1-GG1 in Mongols, G1-GG265 in Armenians and its
      distant brother clade G1-GG162 in Bashkirs, and G1-GG362 in West Indians. The
      haplotype diversity, which decreased from West Iran to Central Asia, allows us to
      hypothesize that this rare haplogroup could have been carried by the expansion of
      Iranic speakers northwards to the Eurasian steppe and via founder effects became
      a predominant genetic component of some populations, including the Argyn tribe of
      the Kazakhs. The remarkable agreement between genetic and genealogical trees of
      Argyns allowed us to calibrate the molecular clock using a historical date (1405
      AD) of the most recent common genealogical ancestor. The mutation rate for Y
      chromosomal sequence data obtained was 0.78*10-9 per bp per year, falling within
      the range of published rates. The mutation rate for Y-chromosomal STRs was 0.0022
      per locus per generation, very close to the so-called genealogical rate. The
      "clan-based" approach to estimating the mutation rate provides a third, middle
      way between direct farther-to-son comparisons and using archeologically known
      migrations, whose dates are subject to revision and of uncertain relationship to
      genetic events. 

PMID- 25849549
TI  - A novel biosurfactant produced by Aureobasidium pullulans L3-GPY from a tiger
      lily wild flower, Lilium lancifolium Thunb.
AB  - Yeast biosurfactants are important biotechnological products in the food
      industry, and they have medical and cosmeceutical applications owing to their
      specific modes of action, low toxicity, and applicability. Thus, we have isolated
      and examined biosurfactant-producing yeast for various industrial and medical
      applications. A rapid and simple method was developed to screen biosurfactant
      producing yeasts for high production of eco-friendly biosurfactants. Using this
      method, several potential niches of biosurfactant-producing yeasts, such as wild
      flowers, were investigated. We successfully selected a yeast strain, L3-GPY, with
      potent surfactant activity from a tiger lily, Lilium lancifolium Thunb. Here, we
      report the first identification of strain L3-GPY as the black yeast Aureobasidium
      pullulans. In addition, we isolated a new low-surface-tension chemical,
      designated glycerol-liamocin, from the culture supernatant of strain L3-GPY
      through consecutive chromatography steps, involving an ODS column, solvent
      partition, silica gel, Sephadex LH-20, and an ODS Sep-Pak cartridge column. The
      chemical structure of glycerol-liamocin, determined by mass spectrometry and
      nuclear magnetic resonance spectroscopy, indicates that it is a novel compound
      with the molecular formula C33H62O12. Furthermore, glycerol-liamocin exhibited
      potent biosurfactant activity (31 mN/m). These results suggest that glycerol
      liamocin is a potential novel biosurfactantfor use in various industrial
      applications. 

PMID- 25849551
TI  - Corrigendum.

PMID- 25849550
TI  - G-CSF protects human brain vascular endothelial cells injury induced by high
      glucose, free fatty acids and hypoxia through MAPK and Akt signaling.
AB  - Granulocyte-colony stimulating factor (G-CSF) has been shown to play a
      neuroprotective role in ischemic stroke by mobilizing bone marrow (BM)-derived
      endothelial progenitor cells (EPCs), promoting angiogenesis, and inhibiting
      apoptosis. Impairments in mobilization and function of the BM-derived EPCs have
      previously been reported in animal and human studies of diabetes where there is
      both reduction in the levels of the BM-derived EPCs and its ability to promote
      angiogenesis. This is hypothesized to account for the pathogenesis of diabetic
      vascular complications such as stroke. Here, we sought to investigate the effects
      of G-CSF on diabetes-associated cerebral vascular defect. We observed that
      pretreatment of the cultured human brain vascular endothelial cells (HBVECs) with
      G-CSF largely prevented cell death induced by the combination stimulus with high
      glucose, free fatty acids (FFA) and hypoxia by increasing cell viability,
      decreasing apoptosis and caspase-3 activity. Cell ultrastructure measured by
      transmission electron microscope (TEM) revealed that G-CSF treatment nicely
      reduced combination stimulus-induced cell apoptosis. The results from fluorescent
      probe Fluo-3/AM showed that G-CSF greatly suppressed the levels of intracellular
      calcium ions under combination stimulus. We also found that G-CSF enhanced the
      expression of cell cycle proteins such as human cell division cycle protein 14A
      (hCdc14A), cyclinB and cyclinE, inhibited p53 activity, and facilitated cell
      cycle progression following combination stimulus. In addition, activation of
      extracellular signal-regulated kinase1/2 (ERK1/2) and Akt, and deactivation of c
      Jun N terminal kinase (JNK) and p38 were proved to be required for the pro
      survival effects of G-CSF on HBVECs exposed to combination stimulus. Overall, G
      CSF is capable of alleviating HBVECs injury triggered by the combination
      administration with high glucose, FFA and hypoxia involving the mitogen-activated
      protein kinases (MAPK) and Akt signaling cascades. G-CSF may represent a
      promising therapeutic agent for diabetic stroke. 

PMID- 25849552
TI  - The evaluation of the risk factors for non-muscle invasive bladder cancer (NMIBC)
      recurrence after transurethral resection (TURBt) in Chinese population.
AB  - OBJECTIVE: The risk factors of bladder cancer recurrence after transurethral
      resection of bladder tumor (TURBt) were poorly understood, especially in Chinese
      population. This study evaluated the potential risk factors of recurrence based
      on a Chinese population. MATERIALS AND METHODS: A total of 698 patients that
      received TURBt procedure in our institute from 2000 to 2012 were recruited in
      this study. Clinical information was collected. The patients were followed up
      according to the schedule recommended by Chinese guideline. RESULTS: A total of
      583 males (83.5%) and 115 females (16.5%) were enrolled in our study. The median
      follow-up duration was 51.5 months. Gender, chief complain, tumor size, number of
      lesions, histological grade and chemotherapeutic agents were found significantly
      associated with patients' short-term recurrence (less than 1 year) (All p<0.05).
      In the multivariate analysis, tumor size, number of lesions, histological grade
      and chemotherapeutic agents were significantly related to patients' short-term
      recurrence (less than 1 year) (All p<0.05). A multivariate model based on tumor
      size, number of lesions, histological grade and chemotherapeutic agents had an
      AUC of 0.697, which significantly improved the prediction utility for bladder
      cancer short-term recurrence (less than 1 year) than any single factor In the
      multivariate Cox regression, tumor size greater than 3 cm, multifocal lesions,
      worsen histological grade and non-urothelial carcinoma was related to time to
      recurrence (TR). CONCLUSION: Patients with larger tumor size, multifocal number
      of lesions, higher tumor grade and who received chemotherapeutic agents other
      than Epirubicin and Pirarubicin might have higher risks of recurrence less than 1
      year. Tumor size, number of lesions, pathology and histological grade might be
      associated with TR. As Bacille Calmette-Guerin (BCG) is currently not approved
      for bladder cancer in China, Epirubicin and Pirarubicin might be considered prior
      to other chemotherapy medications when providing post-operative instillation of
      chemotherapy.

PMID- 25849553
TI  - Metrics for assessing cytoskeletal orientational correlations and consistency.
AB  - In biology, organization at multiple scales potentiates biological function.
      Current advances in staining and imaging of biological tissues provide a wealth
      of data, but there are few metrics to quantitatively describe these findings. In
      particular there is a need for a metric that would characterize the correlation
      and consistency of orientation of different biological constructs within a
      tissue. We aimed to create such a metric and to demonstrate its use with images
      of cardiac tissues. The co-orientational order parameter (COOP) was based on the
      mathematical framework of a classical parameter, the orientational order
      parameter (OOP). Theorems were proven to illustrate the properties and boundaries
      of the COOP, which was then applied to both synthetic and experimental data. We
      showed the COOP to be useful for quantifying the correlation of orientation of
      constructs such as actin filaments and sarcomeric Z-lines. As expected, cardiac
      tissues showed perfect correlation between actin filaments and Z-lines. We also
      demonstrated the use of COOP to quantify the consistency of construct orientation
      within cells of the same shape. The COOP provides a quantitative tool to
      characterize tissues beyond co-localization or single construct orientation
      distribution. In the future, this new parameter could be used to represent the
      quantitative changes during maturation of cardiac tissue, pathological
      malformation, and other processes. 

PMID- 25849554
TI  - New point mutations in surface and core genes of hepatitis B virus associated
      with acute on chronic liver failure identified by complete genomic sequencing.
AB  - The objective of this study was to identify new viral biomarkers associated with
      acute on chronic liver failure (ACLF) by complete genomic sequencing of HBV.
      Hepatitis B virus mutations associated with ACLF were screened by Illumina high
      throughput sequencing in twelve ACLF cases and twelve age-matched mild chronic
      hepatitis B patients, which were validated in 438 chronic hepatitis B patients
      (80 asymptomatic carriers, 152 mild chronic hepatitis B patients, 102 severe
      chronic hepatitis B patients and 104 ACLF patients) by direct sequencing. The
      results of Illumina sequencing showed that the mutations at 7 sites (T216C,
      G285A, A1846T, G1896A, C1913A/G, A2159G, and A2189C) of 12 ACLF patients were
      significantly higher than those of 12 controls. In the validation cohorts, a
      significantly higher ratio of genotype B to C was found in patients with ACLF
      than in patients with non-ACLF. Multivariate analysis showed that T216C, G1896A,
      C1913A/G and A2159G/C were independent risk factors for ACLF. C216 in any
      combination, A/G1913 in any combination, and G/C2159 in any combination had high
      specificity for ACLF. In summary, T216C and A2159G/C mutations were novel factors
      independently associated with ACLF. Combined mutations in hepatitis B cases could
      play important roles in ACLF development. 

PMID- 25849555
TI  - Helping reasoners succeed in the Wason selection task: when executive learning
      discourages heuristic response but does not necessarily encourage logic.
AB  - Reasoners make systematic logical errors by giving heuristic responses that
      reflect deviations from the logical norm. Influential studies have suggested
      first that our reasoning is often biased because we minimize cognitive effort to
      surpass a cognitive conflict between heuristic response from system 1 and
      analytic response from system 2 thinking. Additionally, cognitive control
      processes might be necessary to inhibit system 1 responses to activate a system 2
      response. Previous studies have shown a significant effect of executive learning
      (EL) on adults who have transferred knowledge acquired on the Wason selection
      task (WST) to another isomorphic task, the rule falsification task (RFT). The
      original paradigm consisted of teaching participants to inhibit a classical
      matching heuristic that sufficed the first problem and led to significant EL
      transfer on the second problem. Interestingly, the reasoning tasks differed in
      inhibiting-heuristic metacognitive cost. Success on the WST requires half
      suppression of the matching elements. In contrast, the RFT necessitates a global
      rejection of the matching elements for a correct answer. Therefore, metacognitive
      learning difficulty most likely differs depending on whether one uses the first
      or second task during the learning phase. We aimed to investigate this difficulty
      and various matching-bias inhibition effects in a new (reversed) paradigm. In
      this case, the transfer effect from the RFT to the WST could be more difficult
      because the reasoner learns to reject all matching elements in the first task. We
      observed that the EL leads to a significant reduction in matching selections on
      the WST without increasing logical performances. Interestingly, the acquired
      metacognitive knowledge was too "strictly" transferred and discouraged matching
      rather than encouraging logic. This finding underlines the complexity of learning
      transfer and adds new evidence to the pedagogy of reasoning. 

PMID- 25849556
TI  - Degradation and mineralization of phenol compounds with goethite catalyst and
      mineralization prediction using artificial intelligence.
AB  - The efficiency of phenol degradation via Fenton reaction using mixture of
      heterogeneous goethite catalyst with homogeneous ferrous ion was analyzed as a
      function of three independent variables, initial concentration of phenol (60 to
      100 mg /L), weight ratio of initial concentration of phenol to that of H2O2 (1: 6
      to 1: 14) and, weight ratio of initial concentration of goethite catalyst to that
      of H2O2 (1: 0.3 to 1: 0.7). More than 90 % of phenol removal and more than 40% of
      TOC removal were achieved within 60 minutes of reaction. Two separate models were
      developed using artificial neural networks to predict degradation percentage by a
      combination of Fe3+ and Fe2+ catalyst. Five operational parameters were employed
      as inputs while phenol degradation and TOC removal were considered as outputs of
      the developed models. Satisfactory agreement was observed between testing data
      and the predicted values (R2Phenol = 0.9214 and R2TOC= 0.9082). 

PMID- 25849557
TI  - The complete chloroplast and mitochondrial genomes of the green macroalga Ulva
      sp. UNA00071828 (Ulvophyceae, Chlorophyta).
AB  - Sequencing mitochondrial and chloroplast genomes has become an integral part in
      understanding the genomic machinery and the phylogenetic histories of green
      algae. Previously, only three chloroplast genomes (Oltmannsiellopsis viridis,
      Pseudendoclonium akinetum, and Bryopsis hypnoides) and two mitochondrial genomes
      (O. viridis and P. akinetum) from the class Ulvophyceae have been published.
      Here, we present the first chloroplast and mitochondrial genomes from the
      ecologically and economically important marine, green algal genus Ulva. The
      chloroplast genome of Ulva sp. was 99,983 bp in a circular-mapping molecule that
      lacked inverted repeats, and thus far, was the smallest ulvophycean plastid
      genome. This cpDNA was a highly compact, AT-rich genome that contained a total of
      102 identified genes (71 protein-coding genes, 28 tRNA genes, and three ribosomal
      RNA genes). Additionally, five introns were annotated in four genes: atpA (1),
      petB (1), psbB (2), and rrl (1). The circular-mapping mitochondrial genome of
      Ulva sp. was 73,493 bp and follows the expanded pattern also seen in other
      ulvophyceans and trebouxiophyceans. The Ulva sp. mtDNA contained 29 protein
      coding genes, 25 tRNA genes, and two rRNA genes for a total of 56 identifiable
      genes. Ten introns were annotated in this mtDNA: cox1 (4), atp1 (1), nad3 (1),
      nad5 (1), and rrs (3). Double-cut-and-join (DCJ) values showed that organellar
      genomes across Chlorophyta are highly rearranged, in contrast to the highly
      conserved organellar genomes of the red algae (Rhodophyta). A phylogenomic
      investigation of 51 plastid protein-coding genes showed that Ulvophyceae is not
      monophyletic, and also placed Oltmannsiellopsis (Oltmannsiellopsidales) and
      Tetraselmis (Chlorodendrophyceae) closely to Ulva (Ulvales) and Pseudendoclonium
      (Ulothrichales).

PMID- 25849558
TI  - Tuberculosis prevention in South Africa.
AB  - BACKGROUND: South Africa has one of the highest per capita rates of tuberculosis
      (TB) incidence in the world. In 2012, the South African government produced a
      National Strategic Plan (NSP) to control the spread of TB with the ambitious aim
      of zero new TB infections and deaths by 2032, and a halving of the 2012 rates by
      2016. METHODS: We used a transmission model to investigate whether the NSP
      targets could be reached if immediate scale up of control methods had happened in
      2014. We explored the potential impact of four intervention portfolios; 1) "NSP"
      represents the NSP strategy, 2) "WHO" investigates increasing antiretroviral
      therapy eligibility, 3) "Novel Strategies" considers new isoniazid preventive
      therapy strategies and HIV "Universal Test and Treat" and 4) "Optimised" contains
      the most effective interventions. FINDINGS: We find that even with this scale-up,
      the NSP targets are unlikely to be achieved. The portfolio that achieved the
      greatest impact was "Optimised", followed closely by "NSP". The "WHO" and "Novel
      Strategies" had little impact on TB incidence by 2050. Of the individual
      interventions explored, the most effective were active case finding and
      reductions in pre-treatment loss to follow up which would have a large impact on
      TB burden. CONCLUSION: Use of existing control strategies has the potential to
      have a large impact on TB disease burden in South Africa. However, our results
      suggest that the South African TB targets are unlikely to be reached without new
      technologies. Despite this, TB incidence could be dramatically reduced by finding
      and starting more TB cases on treatment.

PMID- 25849561
TI  - Direct and two-step bioorthogonal probes for Bruton's tyrosine kinase based on
      ibrutinib: a comparative study.
AB  - Ibrutinib is a covalent and irreversible inhibitor of Bruton's tyrosine kinase
      (BTK) and has been approved for the treatment of haematological malignancies,
      such as chronic lymphocytic leukaemia, mantle cell lymphoma and Waldenstrom's
      macroglobulinemia. The covalent and irreversible nature of its molecular mode of
      action allows identification and monitoring of its target in an activity-based
      protein profiling (ABPP) setting. Fluorescent and biotinylated ibrutinib
      derivatives have appeared in the literature in recent years to monitor BTK in
      vitro and in situ. The work described here complements this existing methodology
      and pertains a comparative study on the efficacy of direct and two-step
      bioorthogonal ABPP of BTK. 

PMID- 25849560
TI  - Evaluation of the medicinal herb Graptopetalum paraguayense as a treatment for
      liver cancer.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is the fifth most common malignancy
      and the third most common cause of cancer-related death worldwide. Sorafenib is
      the only drug for patients with advanced-stage hepatocellular carcinoma (HCC)
      that has been shown to confer a survival benefit to patients with HCC; however,
      it has many side effects. Thus, alternate therapeutic strategies with improved
      safety and therapeutic efficacy for the management of HCC should be developed.
      METHODS AND FINDINGS: We demonstrate that an extract of Graptopetalum
      paraguayense (GP) down-regulated the expression levels of several onco-proteins,
      including AURKA, AURKB, and FLJ10540, in HCC cells. To isolate the active
      components in the GP extracts, we prepared extracts fractions and assessed their
      effects on the expression of onco-proteins in HCC cells. The fraction designated
      HH-F3 was enriched in active ingredients, exhibited cytotoxic effects, and
      suppressed the expression of the onco-proteins in HCC cells. The structure of the
      main active compound in HH-F3 was found to be similar to that of the
      proanthocyanidin compounds derived from Rhodiola rosea. In addition, a distinct
      new compound rich in 3, 4, 5-trihydroxy benzylic moieties was identified in the
      HH-F3 preparations. Mechanistic studies indicated that HH-F3 induced apoptosis in
      HCC cells by promoting the loss of mitochondrial membrane potential and the
      production of reactive oxygen species. HH-F3 also enhanced PTEN expression and
      decreased AKT phosphorylation at Ser473 in a concentration-dependent manner in
      HCC cells. Moreover combination of GP or HH-F3 and sorafenib synergistically
      inhibits the proliferation of Huh7 cells. The treatment of a rat model with
      diethylnitrosamine (DEN)-induced liver cancer with extracts of GP and HH-F3
      decreased hepatic collagen contents and inhibited tumor growth. CONCLUSIONS:
      These results indicate that GP extracts and HH-F3 can protect the liver by
      suppressing tumor growth; consequently, these compounds could be considered for
      the treatment of HCC.

PMID- 25849559
TI  - Patient-derived xenograft models of breast cancer and their predictive power.
AB  - Despite advances in the treatment of patients with early and metastatic breast
      cancer, mortality remains high due to intrinsic or acquired resistance to
      therapy. Increased understanding of the genomic landscape through massively
      parallel sequencing has revealed somatic mutations common to specific subtypes of
      breast cancer, provided new prognostic and predictive markers, and highlighted
      potential therapeutic targets. Evaluating new targets using established cell
      lines is limited by the inexact correlation between responsiveness observed in
      cell lines versus that elicited in the patient. Patient-derived xenografts (PDXs)
      generated from fresh tumor specimens recapitulate the diversity of breast cancer
      and reflect histopathology, tumor behavior, and the metastatic properties of the
      original tumor. The high degree of genomic preservation evident across primary
      tumors and their matching PDXs over serial passaging validate them as important
      preclinical tools. Indeed, there is accumulating evidence that PDXs can
      recapitulate treatment responses of the parental tumor. The finding that tumor
      engraftment is an independent and poor prognostic indicator of patient outcome
      represents the first step towards personalized medicine. Here we review the
      utility of breast cancer PDX models to study the clonal evolution of tumors and
      to evaluate novel therapies and drug resistance. 

PMID- 25849562
TI  - Nucleosides present on phlebotomine saliva induce immunossuppression and promote
      the infection establishment.
AB  - BACKGROUND: Sand fly saliva plays a crucial role in establishing Leishmania
      infection. We identified adenosine (ADO) and adenosine monophosphate (AMP) as
      active pharmacologic compounds present in Phlebotomus papatasi saliva that
      inhibit dendritic cell (DC) functions through a PGE2/IL 10-dependent mechanism.
      METHODOLOGY/PRINCIPAL FINDINGS: Herein, we prepared a mixture of ADO and AMP in
      equimolar amounts similar to those present in the salivary-gland extract (SGE)
      form one pair of salivary glands of P. papatasi and co-injected it with
      Leishmania amazonensis or L. major into mouse ears. ADO+AMP mimicked exacerbative
      effects of P. papatasi saliva in leishmaniasis, increasing parasite burden and
      cutaneous lesions. Enzymatic catabolism of salivary nucleosides reversed the SGE
      induced immunosuppressive effect associated with IL-10 enhancement.
      Immunosuppressive factors COX2 and IL-10 were upregulated and failed to enhance
      ear lesion and parasite burden in IL 10-/- infected mice. Furthermore,
      nucleosides increased regulatory T cell (Treg) marker expression on CD4+CD25-
      cells, suggesting induction of Tregs on effector T cells (T eff). Treg induction
      (iTreg) was associated with nucleoside-induced tolerogenic dendritic cells (tDCs)
      expressing higher levels of COX2 and IL-10. In vitro generation of Tregs was more
      efficient in DCs treated with nucleosides. Suppressive effects of nucleosides
      during cutaneous leishmaniasis were mediated through an A2AR-dependent mechanism.
      Using BALB/c mice deficient in A2A ADO receptor (A2AR-/-), we showed that co
      inoculated mice controlled infection, displaying lower parasite numbers at
      infection sites and reduced iTreg generation. CONCLUSION/SIGNIFICANCE: We have
      demonstrated that ADO and AMP in P. papatasi saliva mediate exacerbative effects
      of Leishmania infection by acting preferentially on DCs promoting a tolerogenic
      profile in DCs and by generating iTregs in inflammatory foci through an A2AR
      mechanism.

PMID- 25849563
TI  - CHADS2 and CHA2DS2-VASc scoring systems for predicting atrial fibrillation
      following cardiac valve surgery.
AB  - OBJECTIVE: Clinical use of CHADS2 and CHA2DS2-VASc scoring systems for predicting
      AF following cardiac surgery have been reported in previous studies and
      demonstrated well-validated predictive value. We sought to investigate whether
      the two scoring systems are effective for predicting new-onset of AF following
      cardiac valve surgery and to demonstrate its potential utility of clinical
      assessment. METHODS: Medical records of all patients underwent cardiac valve
      surgeries during the period of January 2003 and December 2013 without
      preoperative AF at the cardiac center of our university were reviewed. The main
      outcome end point of our study was the early new-onset of AF following cardiac
      valve surgery. RESULTS: There were overall 518 patients involved in this study,
      with 234 (45.17%) developed POAF following valve surgery. Patients with POAF had
      older age (P=0.23) and higher BMI (P=0.013) than those without POAF. History of
      heart failure (P=0.025), hypertension (P=0.021), previous stroke or TIA
      (P=0.032), coronary artery disease (P=0.001), carotid artery disease (P=0.024)
      and preoperative medication of statins (P=0.021) were significantly more recorded
      in POAF group. Patients with POAF also had higher LAD (P=0.013) and E/e' ratio
      (P<0.001). The CHADS2 and CHA2DS2-VASc scores were significantly higher in
      patients with POAF (P=0.002; P<0.001), and under univariate and multivariate
      regression analysis the CHADS2 and CHA2DS2-VASc scores were significant
      predictors of POAF (P=0.001; P<0.001). Based on stratification of CHADS2 and
      CHA2DS2-VASc scores, the Kaplan-Meier analysis obtained a higher POAF rate on
      patients with higher stratification of CHADS2 and CHA2DS2-VASc scores (P<0.001;
      P<0.001). CONCLUSION: In conclusion, CHADS2 and CHA2DS2-VASc scores were directly
      associated with the incidence of POAF following valve surgery and a higher score
      was strongly predictive of POAF.

PMID- 25849564
TI  - Comprehensive identification of arginine methylation in primary T cells reveals
      regulatory roles in cell signalling.
AB  - The impact of protein arginine methylation on the regulation of immune functions
      is virtually unknown. Here, we apply a novel method-isomethionine methyl-SILAC
      coupled with antibody-mediated arginine-methylated peptide enrichment to identify
      methylated peptides in human T cells by mass spectrometry. This approach allowed
      the identification of 2,502 arginine methylation sites from 1,257 tissue-specific
      and housekeeping proteins. We find that components of T cell antigen receptor
      signal machinery and several key transcription factors that regulate T cell fate
      determination are methylated on arginine. Moreover, we demonstrate changes in
      arginine methylation stoichiometry during cellular stimulation in a subset of
      proteins critical to T cell differentiation. Our data suggest that protein
      arginine methyltransferases exert key regulatory roles in T cell activation and
      differentiation, opening a new field of investigation in T cell biology.

PMID- 25849565
TI  - Use of learning media by undergraduate medical students in pharmacology: a
      prospective cohort study.
AB  - The ubiquity of the internet and computer-based technologies has an increasing
      impact on higher education and the way students access information for learning.
      Moreover, there is a paucity of information about the quantitative and
      qualitative use of learning media by the current student generation. In this
      study we systematically analyzed the use of digital and non-digital learning
      resources by undergraduate medical students. Daily online surveys and semi
      structured interviews were conducted with a cohort of 338 third year medical
      students enrolled in a general pharmacology course. Our data demonstrate a
      predominant use of digital over non-digital learning resources (69 +/- 7% vs. 31
      +/- 7%; p < 0.01) by students. Most used media for learning were lecture slides
      (26.8 +/- 3.0%), apps (22.0 +/- 3.7%) and personal notes (15.5 +/- 2.7%),
      followed by textbooks (> 300 pages) (10.6 +/- 3.3%), internet search (7.9 +/-
      1.6%) and e-learning cases (7.6 +/- 3.0%). When comparing learning media use of
      teaching vs. pre-exam self-study periods, textbooks were used significantly less
      during self-study (-55%; p < 0.01), while exam questions (+334%; p < 0.01) and e
      learning cases (+176%; p < 0.01) were utilized more. Taken together, our study
      revealed a high prevalence and acceptance of digital learning resources by
      undergraduate medical students, in particular mobile applications. 

PMID- 25849566
TI  - Global epidemiology of type 1 diabetes in young adults and adults: a systematic
      review.
AB  - BACKGROUND: Although type 1 diabetes (T1D) can affect patients of all ages, most
      epidemiological studies of T1D focus on disease forms with clinical diagnosis
      during childhood and adolescence. Clinically, adult T1D is difficult to
      discriminate from certain forms of Type 2 Diabetes (T2D) and from Latent
      Autoimmune Diabetes in Adults (LADA). METHODS: A systematic review of the
      literature was performed to retrieve original papers in English, French and
      Spanish published up to November 6, 2014, reporting the incidence of T1D among
      individuals aged over 15 years. The study was carried out according to the PRISMA
      recommendations. RESULTS: We retrieved information reporting incidence of T1D
      among individuals aged more than 15 years in 35 countries, and published in 70
      articles between 1982 and 2014. Specific anti-beta-cell proteins or C-peptide
      detection were performed in 14 of 70 articles (20%). The most frequent diagnostic
      criteria used were clinical symptoms and immediate insulin therapy. Country-to
      country variations of incidence in those aged >15 years paralleled those of
      children in all age groups. T1D incidence was larger in males than in females in
      44 of the 54 (81%) studies reporting incidence by sex in people >15 years of age.
      The overall mean male-to-female ratio in the review was 1.47 (95% CI = 1.33-1.60,
      SD = 0.49, n = 54, p = <0.0001). Overall, T1D incidence decreased in adulthood,
      after the age of 14 years. CONCLUSIONS: Few studies on epidemiology of T1D in
      adults are available worldwide, as compared to those reporting on children with
      T1D. The geographical variations of T1D incidence in adults parallel those
      reported in children. As opposed to what is known in children, the incidence is
      generally larger in males than in females. There is an unmet need to evaluate the
      incidence of autoimmune T1D in adults, using specific autoantibody detection, and
      to better analyze epidemiological specificities - if any - of adult T1D. PROSPERO
      REGISTRATION NUMBER: CRD42012002369.

PMID- 25849567
TI  - Spatial analysis of Schistosomiasis in Hubei Province, China: a GIS-based
      analysis of Schistosomiasis from 2009 to 2013.
AB  - BACKGROUND: Schistosomiasis remains a major public health problem in China. The
      major endemic areas are located in the lake and marshland regions of southern
      China, particularly in areas along the middle and low reach of the Yangtze River.
      Spatial analytical techniques are often used in epidemiology to identify spatial
      clusters in disease regions. This study assesses the spatial distribution of
      schistosomiasis and explores high-risk regions in Hubei Province, China to
      provide guidance on schistosomiasis control in marshland regions. METHODS: In
      this study, spatial autocorrelation methodologies, including global Moran's I and
      local Getis-Ord statistics, were utilized to describe and map spatial clusters
      and areas where human Schistosoma japonicum infection is prevalent at the county
      level in Hubei province. In addition, linear logistic regression model was used
      to determine the characteristics of spatial autocorrelation with time. RESULTS:
      The infection rates of S. japonicum decreased from 2009 to 2013. The global
      autocorrelation analysis results on the infection rate of S. japonicum for five
      years showed statistical significance (Moran's I > 0, P < 0.01), which suggested
      that spatial clusters were present in the distribution of S. japonicum infection
      from 2009 to 2013. Local autocorrelation analysis results showed that the number
      of highly aggregated areas ranged from eight to eleven within the five-year
      analysis period. The highly aggregated areas were mainly distributed in eight
      counties. CONCLUSIONS: The spatial distribution of human S. japonicum infections
      did not exhibit a temporal change at the county level in Hubei Province. The risk
      factors that influence human S. japonicum transmission may not have changed after
      achieving the national criterion of infection control. The findings indicated
      that spatial-temporal surveillance of S. japonicum transmission plays a
      significant role on schistosomiasis control. Timely and integrated prevention
      should be continued, especially in the Yangtze River Basin of Jianghan Plain
      area.

PMID- 25849568
TI  - What are priorities for deprescribing for elderly patients? Capturing the voice
      of practitioners: a modified delphi process.
AB  - Polypharmacy and inappropriate medication use among older adults contribute to
      adverse drug reactions, falls, cognitive impairment, noncompliance,
      hospitalization and mortality. While deprescribing - tapering, reducing or
      stopping a medication - is feasible and relatively safe, clinicians find it
      difficult to carry out. Deprescribing guidelines would facilitate this process.
      The aim of this paper is to identify and prioritize medication classes where
      evidence-based deprescribing guidelines would be of benefit to clinicians. A
      modified Delphi approach included a literature review to identify potentially
      inappropriate medications for the elderly, an expert panel to develop survey
      content and three survey rounds to seek consensus on priorities. Panel
      participants included three pharmacists, two family physicians and one social
      scientist. Sixty-five Canadian geriatrics experts (36 pharmacists, 19 physicians
      and 10 nurse practitioners) participated in the survey. Twenty-nine drugs/drug
      classes were included in the first survey with 14 reaching the required (>= 70%)
      level of consensus, and 2 new drug classes added from qualitative comments. Fifty
      three participants completed round two, and 47 participants completed round
      three. The final five priorities were benzodiazepines, atypical antipsychotics,
      statins, tricyclic antidepressants, and proton pump inhibitors; nine other drug
      classes were also identified as being in need of evidence-based deprescribing
      guidelines. The Delphi consensus process identified five priority drug classes
      for which expert clinicians felt guidance is needed for deprescribing. The
      classes of drugs that emerged strongly from the rankings dealt with mental
      health, cardiovascular, gastroenterological, and neurological conditions. The
      results suggest that deprescribing and overtreatment occurs through the full
      spectrum of primary care, and that evidence-based deprescribing guidelines are a
      priority in the care of the elderly. 

PMID- 25849570
TI  - Correction: pollution breaks down the genetic architecture of life history traits
      in Caenorhabditis elegans.

PMID- 25849569
TI  - Interactive and independent associations between the socioeconomic and objective
      built environment on the neighbourhood level and individual health: a systematic
      review of multilevel studies.
AB  - BACKGROUND: The research question how contextual factors of neighbourhood
      environments influence individual health has gained increasing attention in
      public health research. Both socioeconomic neighbourhood characteristics and
      factors of the built environment play an important role for health and health
      related behaviours. However, their reciprocal relationships have not been
      systematically reviewed so far. This systematic review aims to identify studies
      applying a multilevel modelling approach which consider both neighbourhood
      socioeconomic position (SEP) and factors of the objective built environment
      simultaneously in order to disentangle their independent and interactive effects
      on individual health. METHODS: The three databases PubMed, PsycINFO, and Web of
      Science were systematically searched with terms for title and abstract screening.
      Grey literature was not included. Observational studies from USA, Canada,
      Australia, New Zealand, and Western European countries were considered which
      analysed simultaneously factors of neighbourhood SEP and the objective built
      environment with a multilevel modelling approach. Adjustment for individual SEP
      was a further inclusion criterion. RESULTS: Thirty-three studies were included in
      qualitative synthesis. Twenty-two studies showed an independent association
      between characteristics of neighbourhood SEP or the built environment and
      individual health outcomes or health-related behaviours. Twenty-one studies found
      cross-level or within-level interactions either between neighbourhood SEP and the
      built environment, or between neighbourhood SEP or the built environment and
      individual characteristics, such as sex, individual SEP or ethnicity. Due to the
      large variation of study design and heterogeneous reporting of results the
      identification of consistent findings was problematic and made quantitative
      analysis not possible. CONCLUSIONS: There is a need for studies considering
      multiple neighbourhood dimensions and applying multilevel modelling in order to
      clarify their causal relationship towards individual health. Especially, more
      studies using comparable characteristics of neighbourhood SEP and the objective
      built environment and analysing interactive effects are necessary to disentangle
      health impacts and identify vulnerable neighbourhoods and population groups.

PMID- 25849571
TI  - Dynamic changes in amino acid concentration profiles in patients with sepsis.
AB  - OBJECTIVES: The goal of this work was to explore the dynamic concentration
      profiles of 42 amino acids and the significance of these profiles in relation to
      sepsis, with the aim of providing guidance for clinical therapies. METHODS:
      Thirty-five critically ill patients with sepsis were included. These patients
      were further divided into sepsis (12 cases) and severe sepsis (23 cases) groups
      or survivor (20 cases) and non-survivor (15 cases) groups. Serum samples from the
      patients were collected on days 1, 3, 5, 7, 10, and 14 following intensive care
      unit (ICU) admission, and the serum concentrations of 42 amino acids were
      measured. RESULTS: The metabolic spectrum of the amino acids changed dramatically
      in patients with sepsis. As the disease progressed further or with poor
      prognosis, the levels of the different amino acids gradually increased,
      decreased, or fluctuated over time. The concentrations of sulfur-containing amino
      acids (SAAs), especially taurine, decreased significantly as the severity of
      sepsis worsened or with poor prognosis of the patient. The serum concentrations
      of SAAs, especially taurine, exhibited weak negative correlations with the
      Sequential Organ Failure Assessment (SOFA) (r=-0.319) and Acute Physiology and
      Chronic Health Evaluation (APACHE) II (r=-0.325) scores. The areas under the
      receiver operating characteristic curves of cystine, taurine, and SAA levels and
      the SOFA and APACHE II scores, which denoted disease prognosis, were 0.623,
      0.674, 0.678, 0.86, and 0.857, respectively. CONCLUSIONS: Critically ill patients
      with disorders of amino acid metabolism, especially of SAAs such as cystine and
      taurine, may provide an indicator of the need for the nutritional support of
      sepsis in the clinic. TRIAL REGISTRATION: ClinicalTrial.gov identifier
      NCT01818830.

PMID- 25849572
TI  - Childhood trauma and personal mastery: their influence on emotional reactivity to
      everyday events in a community sample of middle-aged adults.
AB  - Childhood trauma is associated with premature declines in health in midlife and
      old age. Pathways that have been implicated, but less studied include social
      emotional regulation, biological programming, and habitual patterns of thought
      and action. In this study we focused on childhood trauma's influence via
      alterations in social-emotional regulation to everyday life events, a pathway
      that has been linked to subsequent health effects. Data from a 30-day daily diary
      of community residents who participated in a study of resilience in Midlife (n =
      191, Mage = 54, SD = 7.50, 54% women) was used to examine whether self-reports of
      childhood trauma were associated with daily well-being, as well as reported and
      emotional reactivity to daily negative and positive events. Childhood trauma
      reports were associated with reporting lower overall levels of and greater
      variability in daily well-being. Childhood trauma was linked to greater reports
      of daily negative events, but not to positive events. Focusing on emotional
      reactivity to daily events, residents who reported higher levels of childhood
      trauma showed stronger decreases in well-being when experiencing negative events
      and also stronger increases in well-being with positive events. For those
      reporting childhood trauma, higher levels of mastery were associated with
      stronger decreases in well-being with negative events and stronger increases in
      well-being with positive events, suggesting that mastery increases sensitivity to
      daily negative and positive events. Our results suggest that childhood trauma may
      lead to poorer health in midlife through disturbances in the patterns of everyday
      life events and responses to those events. Further, our findings indicate that
      mastery may have a different meaning for those who experienced childhood trauma.
      We discuss social-emotional regulation as one pathway linking childhood trauma to
      health, and psychosocial resources to consider when building resilience-promoting
      interventions for mitigating the detrimental health effects of childhood trauma. 

PMID- 25849573
TI  - Integration of transcriptome and whole genomic resequencing data to identify key
      genes affecting swine fat deposition.
AB  - Fat deposition is highly correlated with the growth, meat quality, reproductive
      performance and immunity of pigs. Fatty acid synthesis takes place mainly in the
      adipose tissue of pigs; therefore, in this study, a high-throughput massively
      parallel sequencing approach was used to generate adipose tissue transcriptomes
      from two groups of Songliao black pigs that had opposite backfat thickness
      phenotypes. The total number of paired-end reads produced for each sample was in
      the range of 39.29-49.36 millions. Approximately 188 genes were differentially
      expressed in adipose tissue and were enriched for metabolic processes, such as
      fatty acid biosynthesis, lipid synthesis, metabolism of fatty acids, etinol,
      caffeine and arachidonic acid and immunity. Additionally, many genetic variations
      were detected between the two groups through pooled whole-genome resequencing.
      Integration of transcriptome and whole-genome resequencing data revealed
      important genomic variations among the differentially expressed genes for fat
      deposition, for example, the lipogenic genes. Further studies are required to
      investigate the roles of candidate genes in fat deposition to improve pig
      breeding programs. 

PMID- 25849574
TI  - The extracytoplasmic linker peptide of the sensor protein SaeS tunes the kinase
      activity required for staphylococcal virulence in response to host signals.
AB  - Bacterial pathogens often employ two-component systems (TCSs), typically
      consisting of a sensor kinase and a response regulator, to control expression of
      a set of virulence genes in response to changing host environments. In
      Staphylococcus aureus, the SaeRS TCS is essential for in vivo survival of the
      bacterium. The intramembrane-sensing histidine kinase SaeS contains, along with a
      C-terminal kinase domain, a simple N-terminal domain composed of two
      transmembrane helices and a nine amino acid-long extracytoplasmic linker peptide.
      As a molecular switch, SaeS maintains low but significant basal kinase activity
      and increases its kinase activity in response to inducing signals such as human
      neutrophil peptide 1 (HNP1). Here we show that the linker peptide of SaeS
      controls SaeS's basal kinase activity and that the amino acid sequence of the
      linker peptide is highly optimized for its function. Without the linker peptide,
      SaeS displays aberrantly elevated kinase activity even in the absence of the
      inducing signal, and does not respond to HNP1. Moreover, SaeS variants with
      alanine substitution of the linker peptide amino acids exhibit altered basal
      kinase activity and/or irresponsiveness to HNP1. Biochemical assays reveal that
      those SaeS variants have altered autokinase and phosphotransferase activities.
      Finally, animal experiments demonstrate that the linker peptide-mediated fine
      tuning of SaeS kinase activity is critical for survival of the pathogen. Our
      results indicate that the function of the linker peptide in SaeS is a highly
      evolved feature with very optimized amino acid sequences, and we propose that, in
      other SaeS-like intramembrane sensing histidine kinases, the extracytoplasmic
      linker peptides actively fine-control their kinases. 

PMID- 25849575
TI  - The good, the bad and the ugly of catheterization practice among elite athletes
      with spinal cord injury.

PMID- 25849577
TI  - Preparation of tertiary amines by the reaction of iminium ions derived from
      unsymmetrical aminals with zinc and magnesium organometallics.
AB  - We report a convenient one-pot preparation of polyfunctional tertiary amines,
      including various biorelevant phenethylamines or ephedrine derivatives, via the
      reaction of new functionalized iminium ions with a variety of zinc and magnesium
      organometallic reagents. These iminium ions were generated from unsymmetrical
      aminals, obtained by the in situ addition of various amides to Tietze's iminium
      salt [Me2NCH2(+)CF3COO(-)]. A functionalized aniline, prepared by this method,
      was converted to a quinolidine via an intramolecular Heck reaction. 

PMID- 25849576
TI  - Sex differences in liver toxicity-do female and male human primary hepatocytes
      react differently to toxicants in vitro?
AB  - There is increasing amount of evidence for sex variation in drug efficiency and
      toxicity profiles. Women are more susceptible than men to acute liver injury from
      xenobiotics. In general, this is attributed to sex differences at a physiological
      level as well as differences in pharmacokinetics and pharmacodynamics, but
      neither of these can give a sufficient explanation for the diverse responses to
      xenobiotics. Existing data are mainly based on animal models and limited data
      exist on in vitro sex differences relevant to humans. To date, male and female
      human hepatocytes have not yet been compared in terms of their responses to
      hepatotoxic drugs. We investigated whether sex-specific differences in acute
      hepatotoxicity can be observed in vitro by comparing hepatotoxic drug effects in
      male and female primary human hepatocytes. Significant sex-related differences
      were found for certain parameters and individual drugs, showing an overall higher
      sensitivity of female primary hepatocytes to hepatotoxicants. Moreover, our work
      demonstrated that high content screening is feasible with pooled primary human
      hepatocytes in suspension. 

PMID- 25849578
TI  - Early life origins of all-cause and cause-specific disability pension: findings
      from the Helsinki Birth Cohort Study.
AB  - BACKGROUND: There is some evidence linking sub-optimal prenatal development to an
      increased risk of disability pension (DP). Our aim was to investigate whether
      body size at birth was associated with transitioning into all-cause and cause
      specific DP during the adult work career. METHODS: 10 682 people born in 1934-44
      belonging to the Helsinki Birth Cohort Study had data on birth weight extracted
      from birth records, and on time, type and reason of retirement between 1971 and
      2011 extracted from the Finnish Centre for Pensions. RESULTS: Altogether 21.3%
      transitioned into DP during the 40-year follow-up, mainly due to mental
      disorders, musculoskeletal disorders and cardiovascular disease. Average age of
      transitioning into DP was 51.3 (SD 8.4) for men and 52.2 (SD 7.6) for women.
      Cohort members who did not transition into DP retired 10 years later on average.
      Among men, higher birth weight was associated with a lower hazard of
      transitioning into DP, adjusted hazard ratio (HR) being 0.94 (95% confidence
      interval [CI] 0.88-0.99 for 1 SD increase in birth weight). For DP due to mental
      disorders the adjusted HR was 0.90, 95% CI 0.81, 0.99. A similar but non
      significant trend was found for DP due to cardiovascular disease. Among women
      there were no associations between body size at birth and all-cause DP (p for
      interaction gender*birth weight on DP p = 0.007). CONCLUSIONS: Among men
      disability pension, particularly due to mental disorders, may have its origins in
      prenatal development. Given that those who retire due to mental health problems
      are relatively young, the loss to the workforce is substantial.

PMID- 25849579
TI  - A transgenic Prox1-Cre-tdTomato reporter mouse for lymphatic vessel research.
AB  - The lymphatic vascular system plays an active role in immune cell trafficking,
      inflammation and cancer spread. In order to provide an in vivo tool to improve
      our understanding of lymphatic vessel function in physiological and pathological
      conditions, we generated and characterized a tdTomato reporter mouse and crossed
      it with a mouse line expressing Cre recombinase under the control of the
      lymphatic specific promoter Prox1 in an inducible fashion. We found that the
      tdTomato fluorescent signal recapitulates the expression pattern of Prox1 in
      lymphatic vessels and other known Prox1-expressing organs. Importantly, tdTomato
      co-localized with the lymphatic markers Prox1, LYVE-1 and podoplanin as assessed
      by whole-mount immunofluorescence and FACS analysis. The tdTomato reporter was
      brighter than a previously established red fluorescent reporter line. We
      confirmed the applicability of this animal model to intravital microscopy of
      dendritic cell migration into and within lymphatic vessels, and to fluorescence
      activated single cell analysis of lymphatic endothelial cells. Additionally, we
      were able to describe the early morphological changes of the lymphatic
      vasculature upon induction of skin inflammation. The Prox1-Cre-tdTomato reporter
      mouse thus shows great potential for lymphatic research. 

PMID- 25849580
TI  - Distinct inhibitory effects on mTOR signaling by ethanol and INK128 in diffuse
      large B-cell lymphoma.
AB  - BACKGROUND: The mechanistic target of rapamycin, (mTOR) kinase plays a pivotal
      role in controlling critical cellular growth and survival pathways, and its
      aberrant induction is implicated in cancer pathogenesis. Therefore, suppression
      of active mTOR signaling has been of great interest to researchers; several mTOR
      inhibitors have been discovered to date. Ethanol (EtOH), similar to pharmacologic
      mTOR inhibitors, has been shown to suppress the mTOR signaling pathway, though in
      a non-catalytic manner. Despite population studies showing that the consumption
      of EtOH has a protective effect against hematological malignancies, the
      mechanisms behind EtOH's modulation of mTOR activity in cells and its downstream
      consequences are largely unknown. Here we evaluated the effects of EtOH on the
      mTOR pathway, in comparison to the active-site mTOR inhibitor INK128, and
      compared translatome analysis of their downstream effects in diffuse large B-cell
      lymphoma (DLBCL). RESULTS: Treatment of DLBCL cells with EtOH suppressed mTORC1
      complex formation while increasing AKT phosphorylation and mTORC2 complex
      assembly. INK128 completely abrogated AKT phosphorylation without affecting the
      structure of mTORC1/2 complexes. Accordingly, EtOH less profoundly suppressed cap
      dependent translation and global protein synthesis, compared to a remarkable
      inhibitory effect of INK128 treatment. Importantly, EtOH treatment induced the
      formation of stress granules, while INK128 suppressed their formation. Microarray
      analysis of polysomal RNA revealed that although both agents primarily affected
      cell growth and survival, EtOH and INK128 regulated the synthesis of mostly
      distinct genes involved in these processes. Though both EtOH and INK128 inhibited
      cell cycle, proliferation and autophagy, EtOH, in contrast to INK128, did not
      induce cell apoptosis. CONCLUSION: Given that EtOH, similar to pharmacologic mTOR
      inhibitors, inhibits mTOR signaling, we systematically explored the effect of
      EtOH and INK128 on mTOR signal transduction, components of the mTORC1/2
      interaction and their downstream effectors in DLBCL malignancy. We found that
      EtOH partially inhibits mTOR signaling and protein translation, compared to
      INK128's complete mTOR inhibition. Translatome analysis of mTOR downstream target
      genes established that differential inhibition of mTOR by EtOH and INK128
      distinctly modulates translation of specific subsets of mRNAs involved in cell
      growth and survival, leading to differential cellular response and survival.

PMID- 25849581
TI  - Quantitative amyloid imaging using image-derived arterial input function.
AB  - Amyloid PET imaging is an indispensable tool widely used in the investigation,
      diagnosis and monitoring of Alzheimer's disease (AD). Currently, a reference
      region based approach is used as the mainstream quantification technique for
      amyloid imaging. This approach assumes the reference region is amyloid free and
      has the same tracer influx and washout kinetics as the regions of interest.
      However, this assumption may not always be valid. The goal of this work is to
      evaluate an amyloid imaging quantification technique that uses arterial region of
      interest as the reference to avoid potential bias caused by specific binding in
      the reference region. 21 participants, age 58 and up, underwent Pittsburgh
      compound B (PiB) PET imaging and MR imaging including a time-of-flight (TOF) MR
      angiography (MRA) scan and a structural scan. FreeSurfer based regional analysis
      was performed to quantify PiB PET data. Arterial input function was estimated
      based on coregistered TOF MRA using a modeling based technique. Regional
      distribution volume (VT) was calculated using Logan graphical analysis with
      estimated arterial input function. Kinetic modeling was also performed using the
      estimated arterial input function as a way to evaluate PiB binding (DVRkinetic)
      without a reference region. As a comparison, Logan graphical analysis was also
      performed with cerebellar cortex as reference to obtain DVRREF. Excellent
      agreement was observed between the two distribution volume ratio measurements
      (r>0.89, ICC>0.80). The estimated cerebellum VT was in line with literature
      reported values and the variability of cerebellum VT in the control group was
      comparable to reported variability using arterial sampling data. This study
      suggests that image-based arterial input function is a viable approach to
      quantify amyloid imaging data, without the need of arterial sampling or a
      reference region. This technique can be a valuable tool for amyloid imaging,
      particularly in population where reference normalization may not be accurate. 

PMID- 25849582
TI  - One-pot, three-component approach to the synthesis of 3,4,5-trisubstituted
      pyrazoles.
AB  - An operationally simple and high yielding protocol for the synthesis of
      polyfunctional pyrazoles has been developed through one-pot, three-component
      coupling of aldehydes, 1,3-dicarbonyls, and diazo compounds as well as tosyl
      hydrazones. The reaction proceeds through a tandem Knoevenagel condensation, 1,3
      dipolar cycloaddition, and transition metal-free oxidative aromatization reaction
      sequence utilizing molecular oxygen as a green oxidant. The scope of the reaction
      was studied by varying the aldehyde, 1,3-dicarbonyl, and diazo component
      individually. 

PMID- 25849584
TI  - Determination of solid state characteristics of spray-congealed Ibuprofen solid
      lipid microparticles and their impact on sustaining drug release.
AB  - This study was used to find solid state characteristics of ibuprofen loaded spray
      congealed solid lipid microparticles (SLMs) by employing simple lipids as
      matrices, with or without polymeric additives, and the impact of solid drug
      matrix miscibility on sustaining drug release. Solid miscibility of ibuprofen
      with two lipids, cetyl alcohol (CA) and stearic acid (SA), were investigated
      using differential scanning calorimetry (DSC). SLMs containing 20% w/w ibuprofen
      with or without polymeric additives, PVP/VA and EC, were produced by spray
      congealing, and the resultant microparticles were subjected to visual examination
      by scanning electron microscopy (SEM), thermal analysis using DSC, and hot-stage
      microscopy. Intermolecular interactions between lipids and drug as well as
      additives were investigated by Fourier-transformed infrared spectroscopy (FTIR)
      and nuclear magnetic resonance spectroscopy (NMR). X-ray diffractometry (XRD) was
      utilized to study polymorphic changes of drug and matrix over the course of a
      year. Ibuprofen was found to depress the melting points of CA and SA in a
      colligative manner, reaching maximum solubility at 10% w/w and 30% w/w for CA and
      SA, respectively. Drug encapsulation efficiencies and yields of spray-congealed
      SLMs containing 20% w/w ibuprofen were consistently high for both lipid matrices.
      CA and SA were found to adopt their stable gamma- and beta-polymorphs,
      respectively, immediately after spray congealing. The spray congealing process
      resulted in ibuprofen adopting an amorphous or poorly crystalline state, with no
      further changes over the course of a year. SEM, DSC, and hot stage microscope
      studies on the SLMs confirmed the formation of a solid dispersion between
      ibuprofen and CA and a solid solution between ibuprofen and SA. SA was found to
      sustain the release of ibuprofen significantly better than CA. PVP/VA and EC
      showed some interactions with CA, which led to an expansion of unit cell
      dimensions of CA upon spray congealing, whereas they showed negligible
      interactions with SA. PVP/VA and EC both hastened drug release in both CA and SA
      matrices, despite PVP/VA being hydrophilic and EC being hydrophobic. CA and SA
      are useful as lipid matrices that do not exhibit polymorphism when spray
      congealed. Sustained release of ibuprofen was achieved with the formation of a
      solid solution with SA. Solid miscibility of drug in lipid matrix has a large
      impact on the ability of the SLMs to sustain the release of a drug. Polymeric
      additives generally disrupted structural integrity of SLMs and led to faster drug
      release. 

PMID- 25849583
TI  - Paraptosis cell death induction by the thiamine analog benfotiamine in leukemia
      cells.
AB  - Benfotiamine is a synthetic thiamine analogue that stimulates transketolase, a
      cellular enzyme essential for glucose metabolism. Currently, benfotiamine is used
      to treat diabetic neuropathy. We recently reported that oral benfotiamine induced
      a temporary but remarkable recovery from acute myeloid leukemia in an elderly
      patient who was ineligible for standard chemotherapy due to dementia and renal
      failure. In the present study we present evidences that benfotiamine possess
      antitumor activity against leukemia cells. In a panel of nine myeloid leukemia
      cell lines benfotiamine impaired the viability of HL-60, NB4, K562 and KG1 cells
      and also inhibited the growing of primary leukemic blasts. The antitumor activity
      of benfotiamine is not mediated by apoptosis, necrosis or autophagy, but rather
      occurs though paraptosis cell death induction. Mechanistic studies revealed that
      benfotiamine inhibited the activity of constitutively active ERK1/2 and
      concomitantly increased the phosphorylation of JNK1/2 kinase in leukemic cells.
      In addition, benfotiamine induced the down regulation of the cell cycle regulator
      CDK3 which resulted in G1 cell cycle arrest in the sensitive leukemic cells.
      Moreover, combination index studies showed that benfotiamine enhanced the
      antiproliferative activities of cytarabine against leukemia cells. These findings
      suggest that benfotiamine has antitumor therapeutic potential. 

PMID- 25849585
TI  - Measurement of glycolysis reactants by high-throughput solid phase extraction
      with tandem mass spectrometry: Characterization of pyrophosphate-dependent
      phosphofructokinase as a case study.
AB  - Glycolysis is a 10-step metabolic pathway involved in producing cellular energy.
      Many tumors exhibit accelerated glycolytic rates, and enzymes that participate in
      this pathway are focal points of cancer research. Here, a novel method for the
      measurement of glycolysis reactants from in vitro samples is presented. Fast and
      direct measurement is achieved by an automated system that couples on-line solid
      phase extraction (SPE) with tandem mass spectrometry (MS/MS). The single
      analytical method enables multiple reactants to be measured concurrently,
      sustains a cycle time of 8s, and permits the measurement of up to 10,000 samples
      per day. Concentration-response curves were conducted using standards for 10
      metabolic intermediates, and the results demonstrate that the detection strategy
      has excellent sensitivity (average limit of detection = 5.4 nM), dynamic range
      (nanomolar to micromolar), and linear response (average R(2) = 0.998). To test
      the analysis method on reactions, pyrophosphate-dependent phosphofructokinase
      (PPi-PFK) was used as a model system. Data that corroborate the activation and
      inhibition of PPi-PFK are presented, and the ways in which SPE-MS/MS simplifies
      experimental design and interpretation are highlighted. In summary, the method
      for measuring metabolic intermediates described here demonstrates unprecedented
      speed, performance, and versatility.

PMID- 25849586
TI  - Cell fate reprogramming by control of intracellular network dynamics.
AB  - Identifying control strategies for biological networks is paramount for practical
      applications that involve reprogramming a cell's fate, such as disease
      therapeutics and stem cell reprogramming. Here we develop a novel network control
      framework that integrates the structural and functional information available for
      intracellular networks to predict control targets. Formulated in a logical
      dynamic scheme, our approach drives any initial state to the target state with
      100% effectiveness and needs to be applied only transiently for the network to
      reach and stay in the desired state. We illustrate our method's potential to find
      intervention targets for cancer treatment and cell differentiation by applying it
      to a leukemia signaling network and to the network controlling the
      differentiation of helper T cells. We find that the predicted control targets are
      effective in a broad dynamic framework. Moreover, several of the predicted
      interventions are supported by experiments. 

PMID- 25849587
TI  - Prevalence and predictors of asymptomatic malaria parasitemia among pregnant
      women in the rural surroundings of Arbaminch Town, South Ethiopia.
AB  - BACKGROUND: In Sub-Saharan African countries, including Ethiopia, malaria in
      pregnancy is a major public health threat which results in significant
      morbidities and mortalities among pregnant women and their fetuses. In malaria
      endemic areas, Plasmodium infections tend to remain asymptomatic yet causing
      significant problems like maternal anemia, low birth weight, premature births,
      and still birth. This study was conducted to determine the prevalence and
      predictors of asymptomatic Plasmodium infection among pregnant women in the rural
      surroundings of Arba Minch Town, Southern Ethiopia. METHODS: A community based
      cross-sectional study comprising multistage sampling was conducted between April
      and June, 2013. Socio-demographic data were collected by using a semi-structured
      questionnaire. Plasmodium infection was diagnosed by using Giemsa-stained blood
      smear microscopy and a rapid diagnostic test (SD BIOLINE Malaria Ag Pf/Pv POCT,
      standard diagnostics, inc., Korea). RESULTS: Of the total 341 pregnant women
      participated in this study, 9.1% (31/341) and 9.7% (33/341) were confirmed to be
      infected with Plasmodium species by microscopy and rapid diagnostic tests (RDTs),
      respectively. The geometric mean of parasite density was 2392 parasites per
      microliter (MUl); 2275/ MUl for P. falciparum and 2032/ MUl for P. vivax.
      Parasitemia was more likely to occur in primigravidae (Adjusted odds ratio (AOR):
      9.4, 95% confidence interval (CI): 4.3-60.5), secundigravidae (AOR: 6.3, 95% CI:
      2.9-27.3), using insecticide treated bed net (ITN) sometimes (AOR: 3.2, 95% CI:
      1.8- 57.9), not using ITN at all (AOR: 4.6, 95% CI: 1.4-14.4) compared to
      multigravidae and using ITN always, respectively. CONCLUSION: Asymptomatic
      malaria in this study is low compared to other studies' findings. Nevertheless,
      given the high risk of malaria during pregnancy, pregnant women essentially be
      screened for asymptomatic Plasmodium infection and be treated promptly via the
      antenatal care (ANC) services.

PMID- 25849588
TI  - Loss-of-function analysis reveals distinct requirements of the translation
      initiation factors eIF4E, eIF4E-3, eIF4G and eIF4G2 in Drosophila
      spermatogenesis.
AB  - In eukaryotes, post-transcriptional regulation of gene expression has a key role
      in many cellular and developmental processes. Spermatogenesis involves a complex
      developmental program that includes changes in cell cycle dynamics and dramatic
      cellular remodeling. Translational control is critical for spermatogenesis in
      Drosophila as many mRNAs synthesized in the spermatocytes are translated only
      much later during spermatid differentiation. Testes-specific translation
      initiation factors eIF4E-3 and eIF4G2 are essential specifically for male
      fertility. However, details of their roles during different stages of
      spermatogenesis are unknown, and the role of canonical translation initiation
      factors in spermatogenesis remains unexplored. In this study, we addressed the
      functional role of eIF4E-1, eIF4E-3, eIF4G and eIF4G2 in testes development and
      formation of mature sperm. Using the UAS-Gal4 system and RNA interference, we
      systematically knocked down these four genes in different stages of germ cell
      development, and in the somatic cells. Our results show that eIF4E-1 function in
      early germ cells and the surrounding somatic cells is critical for
      spermatogenesis. Both eIF4E-1 and eIF4E-3 are required in spermatocytes for
      chromosome condensation and cytokinesis during the meiotic stages. Interestingly,
      we find that eIF4G knockdown did not affect male fertility while eIF4G2 has
      distinct functions during spermatogenesis; it is required in early germ cells for
      proper meiotic divisions and spermatid elongation while its abrogation in
      spermatocytes caused meiotic arrest. Double knockdown of eIF4G and eIF4G2 shows
      that these proteins act redundantly during the early stages of spermatogenesis.
      Taken together, our analysis reveals spatio-temporal roles of the canonical and
      testes-specific translation initiation factors in coordinating developmental
      programs during spermatogenesis. 

PMID- 25849589
TI  - Genome-wide analysis of the AP2/ERF family in Eucalyptus grandis: an intriguing
      over-representation of stress-responsive DREB1/CBF genes.
AB  - BACKGROUND: The AP2/ERF family includes a large number of developmentally and
      physiologically important transcription factors sharing an AP2 DNA-binding
      domain. Among them DREB1/CBF and DREB2 factors are known as master regulators
      respectively of cold and heat/osmotic stress responses. EXPERIMENTAL APPROACHES:
      The manual annotation of AP2/ERF family from Eucalyptus grandis, Malus, Populus
      and Vitis genomes allowed a complete phylogenetic study for comparing the
      structure of this family in woody species and the model Arabidopsis thaliana.
      Expression profiles of the whole groups of EgrDREB1 and EgrDREB2 were
      investigated through RNAseq database survey and RT-qPCR analyses. RESULTS: The
      structure and the size of the AP2/ERF family show a global conservation for the
      plant species under comparison. In addition to an expansion of the ERF subfamily,
      the tree genomes mainly differ with respect to the group representation within
      the subfamilies. With regard to the E. grandis DREB subfamily, an obvious feature
      is the presence of 17 DREB1/CBF genes, the maximum reported to date for
      dicotyledons. In contrast, only six DREB2 have been identified, which is similar
      to the other plants species under study, except for Malus. All the DREB1/CBF and
      DREB2 genes from E. grandis are expressed in at least one condition and all are
      heat-responsive. Regulation by cold and drought depends on the genes but is not
      specific of one group; DREB1/CBF group is more cold-inducible than DREB2 which is
      mainly drought responsive. CONCLUSION: These features suggest that the dramatic
      expansion of the DREB1/CBF group might be related to the adaptation of this
      evergreen tree to climate changes when it expanded in Australia.

PMID- 25849591
TI  - Compositional engineering of perovskite oxides for highly efficient oxygen
      reduction reactions.
AB  - Mixed conducting perovskite oxides are promising catalysts for high-temperature
      oxygen reduction reaction. Pristine SrCoO(3-delta) is a widely used parent oxide
      for the development of highly active mixed conductors. Doping a small amount of
      redox-inactive cation into the B site (Co site) of SrCoO(3-delta) has been
      applied as an effective way to improve physicochemical properties and
      electrochemical performance. Most findings however are obtained only from
      experimental observations, and no universal guidelines have been proposed. In
      this article, combined experimental and theoretical studies are conducted to
      obtain fundamental understanding of the effect of B-site doping concentration
      with redox-inactive cation (Sc) on the properties and performance of the
      perovskite oxides. The phase structure, electronic conductivity, defect
      chemistry, oxygen reduction kinetics, oxygen ion transport, and electrochemical
      reactivity are experimentally characterized. In-depth analysis of doping level
      effect is also undertaken by first-principles calculations. Among the
      compositions, SrCo0.95Sc0.05O(3-delta) shows the best oxygen kinetics and
      corresponds to the minimum fraction of Sc for stabilization of the oxygen-vacancy
      disordered structure. The results strongly support that B-site doping of SrCoO(3
      delta) with a small amount of redox-inactive cation is an effective strategy
      toward the development of highly active mixed conducting perovskites for
      efficient solid oxide fuel cells and oxygen transport membranes.

PMID- 25849590
TI  - TGF-beta1-mediated differentiation of fibroblasts is associated with increased
      mitochondrial content and cellular respiration.
AB  - OBJECTIVS: Cytokine-dependent activation of fibroblasts to myofibroblasts, a key
      event in fibrosis, is accompanied by phenotypic changes with increased secretory
      and contractile properties dependent on increased energy utilization, yet changes
      in the energetic profile of these cells are not fully described. We hypothesize
      that the TGF-beta1-mediated transformation of myofibroblasts is associated with
      an increase in mitochondrial content and function when compared to naive
      fibroblasts. METHODS: Cultured NIH/3T3 mouse fibroblasts treated with TGF-beta1,
      a profibrotic cytokine, or vehicle were assessed for transformation to
      myofibroblasts (appearance of alpha-smooth muscle actin [alpha-SMA] stress
      fibers) and associated changes in mitochondrial content and functions using laser
      confocal microscopy, Seahorse respirometry, multi-well plate reader and
      biochemical protocols. Expression of mitochondrial-specific proteins was
      determined using western blotting, and the mitochondrial DNA quantified using
      Mitochondrial DNA isolation kit. RESULTS: Treatment with TGF-beta1 (5 ng/mL)
      induced transformation of naive fibroblasts into myofibroblasts with a threefold
      increase in the expression of alpha-SMA (6.85 +/- 0.27 RU) compared to cells not
      treated with TGF-beta1 (2.52 +/- 0.11 RU). TGF-beta1 exposure increased the
      number of mitochondria in the cells, as monitored by membrane potential sensitive
      dye tetramethylrhodamine, and expression of mitochondria-specific proteins;
      voltage-dependent anion channels (0.54 +/- 0.05 vs. 0.23 +/- 0.05 RU) and adenine
      nucleotide transporter (0.61 +/- 0.11 vs. 0.22 +/- 0.05 RU), as well as
      mitochondrial DNA content (530 +/- 12 MUg DNA/106 cells vs. 307 +/- 9 MUg DNA/106
      cells in control). TGF-beta1 treatment was associated with an increase in
      mitochondrial function with a twofold increase in baseline oxygen consumption
      rate (2.25 +/- 0.03 vs. 1.13 +/- 0.1 nmol O2/min/106 cells) and FCCP-induced
      mitochondrial respiration (2.87 +/- 0.03 vs. 1.46 +/- 0.15 nmol O2/min/106
      cells). CONCLUSIONS: TGF-beta1 induced differentiation of fibroblasts is
      accompanied by energetic remodeling of myofibroblasts with an increase in
      mitochondrial respiration and mitochondrial content.

PMID- 25849592
TI  - Is psychiatry only neurology? Or only abnormal psychology? Deja vu after 100
      years.
AB  - Forgetting history, which frequently repeats itself, is a mistake. In General
      Psychopathology, Jaspers criticised early 20th century psychiatrists, including
      those who thought psychiatry was only neurology (Wernicke) or only abnormal
      psychology (Freud), or who did not see the limitations of the medical model in
      psychiatry (Kraepelin). Jaspers proposed that some psychiatric disorders follow
      the medical model (Group I), while others are variations of normality (Group
      III), or comprise schizophrenia and severe mood disorders (Group II). In the
      early 21st century, the players' names have changed but the game remains the
      same. The US NIMH is reprising both Wernicke's brain mythology and Kraepelin's
      marketing promises. The neo-Kraepelinian revolution started at Washington
      University, became pre-eminent through the DSM-III developed by Spitzer, but
      reached a dead end with the DSM-5. McHugh, who described four perspectives in
      psychiatry, is the leading contemporary representative of the Jaspersian
      diagnostic approach. Other neo-Jaspersians are: Berrios, Wiggins and Schwartz,
      Ghaemi, Stanghellini, Parnas and Sass. Can psychiatry learn from its mistakes?
      The current psychiatric language, organised at its three levels, symptoms,
      syndromes, and disorders, was developed in the 19th century but is obsolete for
      the 21st century. Scientific advances in Jaspers' Group III disorders require
      collaborating with researchers in the social and psychological sciences. Jaspers'
      Group II disorders, redefined by the author as schizophrenia, catatonic
      syndromes, and severe mood disorders, are the core of psychiatry. Scientific
      advancement in them is not easy because we are not sure how to delineate between
      and within them correctly.

PMID- 25849593
TI  - Correction: imatinib ameliorates neuroinflammation in a rat model of multiple
      sclerosis by enhancing blood-brain barrier integrity and by modulating the
      peripheral immune response.

PMID- 25849594
TI  - Exploring how pain leads to productivity loss in primary care consulters for
      osteoarthritis: a prospective cohort study.
AB  - OBJECTIVE: Osteoarthritis pain has become a leading cause of decreased
      productivity and work disability in older workers, a major concern in primary
      care. How osteoarthritis pain leads to decreased productivity at work is unclear;
      the aim of this study was to elucidate causal mechanisms and thus identify
      potential opportunities for intervention. METHODS: Population-based prospective
      cohort study of primary care consulters with osteoarthritis. Path analysis was
      used to test proposed mechanisms by examining the association between pain at
      baseline, and onset of work productivity loss at three years for mediation by
      physical limitation, depression, poor sleep and poor coping mechanisms. RESULTS:
      High pain intensity was associated with onset of work productivity loss (Adjusted
      Odds Ratio 2.5; 95%CI 1.3, 4.8). About half of the effect of pain on work
      productivity was a direct effect, and half was mediated by the impact of pain on
      physical function. Depression, poor sleep quality and poor coping did not mediate
      the association between high pain intensity and onset of work productivity loss.
      CONCLUSIONS: As pain is a major cause of work productivity loss, results suggest
      that decreasing pain should be a major focus. However, successfully improving
      function may have an indirect effect by decreasing the impact of pain on work
      productivity, especially important as significant pain reduction is often
      difficult to achieve. Although depression, sleep problems, and coping strategies
      may be directly related to work productivity loss, addressing these issues may
      not have much effect on the significant impact of pain on work productivity.

PMID- 25849595
TI  - LAPTM4B-35, a cancer-related gene, is associated with poor prognosis in TNM
      stages I-III gastric cancer patients.
AB  - BACKGROUND: Lysosome-associated transmembrane protein 4beta-35 (LAPTM4B-35), a
      member of the mammalian 4-tetratransmembrane spanning protein superfamily, has
      been reported to be overexpressed in several cancers. However the expression of
      LAPTM4B-35 and its role in the progression of gastric cancer (GC) remains
      unknown. The aim of this study was to investigate LAPTM4B-35 expression in GC,
      its potential relevance to clinicopathologic parameters and role of LAPTM4B-35
      during gastric carcinogenesis. METHODS: In the present study, paraffin-embedded
      specimens with GC (n = 240, including 180 paired specimens) and 24 paired fresh
      frozen tissues were analyzed. qRT-PCR and immunohistochemistry (IHC) were used to
      analyze the expression of LAPTM4B-35 in GC. The effects of LAPTM4B-35 on GC cell
      proliferation, migration and invasion were determined by overexpression and
      knockdown assays. RESULTS: IHC showed that LAPTM4B-35 was expressed in 68.3%
      (123/180) of GC tissues, while in 16.1% (29/180) of their paired adjacent
      noncancerous gastric tissues (P = 0.000). LAPTM4B-35 mRNA levels in GC tissues
      were also significantly elevated when compared with their paired adjacent
      noncancerous tissues (P = 0.017). Overexpression of LAPTM4B-35 was significantly
      associated with degree of differentiation, depth of invasion, lymphovascular
      invasion and lymph node metastasis (P<0.05). Kaplan-Meier survival curves
      revealed that patients with LAPTM4B-35 expression had a significant decrease in
      overall survival (OS) in stages I-III GC patients (P = 0.006). Multivariate
      analysis showed high expression of LAPTM4B-35 was an independent prognostic
      factor for OS in stage I-III GC patients (P = 0.025). CONCLUSION: These findings
      indicate that LAPTM4B-35 overexpression may be related to GC progression and poor
      prognosis, and thus may serve as a new prediction marker of prognosis in GC
      patients.

PMID- 25849597
TI  - Role of adiponectin and free fatty acids on the association between abdominal
      visceral fat and insulin resistance.
AB  - BACKGROUND: Experimental studies have shown that high free fatty acid (FFA) and
      low adiponectin (ADIPO) levels are involved in the mechanisms by which adiposity
      promotes insulin resistance (IR). However, no previous clinical studies have
      simultaneously analysed the relative contribution of FFA and ADIPO levels on the
      relation of abdominal visceral fat (AVF) with insulin resistance. OBJECTIVE: To
      analyse the contribution of low ADIPO (adiponectin < =p25th: 8.67 MUg/mL in women
      and 5.30 MUg/mL in men), and high FFAs (FFAs > =p75th: 0.745 mEq/L in women and
      0.60 mEq/L in men) to the association of high AVF (AVF > =p75th: 127 cm2 in
      women; 152.7 cm2 in men) with insulin resistance (HOMA-IR > =75th: 3.58 in women
      and 3.12 in men), in non-diabetic subjects. MATERIAL AND METHODS: A cross
      sectional analysis was performed including 1217 control participants of the
      Genetics of Atherosclerotic Disease study (GEA). Clinical, tomographic and
      biochemical parameters were measured in all participants. Logistic regression
      models were used to assess the association of high AVF with IR stratifying
      according to gender, and to normal or low ADIPO and normal or high FFA serum
      levels. RESULTS: In comparison to referent group, in men low ADIPO unlike high
      FFA increased the risk of IR. Females with normal AVF and low ADIPO, or high AVF
      and normal ADIPO had aprox 3 folds risk of IR (OR [IC95%]: 3.7 [2.1-6.6], p <
      0.001, and 3.4 [2.0-5.7], p < 0.001; respectively). The risk increased to 7.6
      [4.2-13.8], p < 0.001 when high AVF and low ADIPO were present. Irrespective of
      AVF, the effect of low ADIPO on IR was higher than that seen for high FFA.
      Besides, our results suggest an additive effect of high AVF, high FFA and low
      ADIPO on the IR prevalence. CONCLUSIONS: The present study provides novel and
      important information about the combined effect of high AVF and low ADIPO on the
      risk of IR. Furthermore, our data suggest that the effect of low adiponectin
      levels on the high AVF-IR association is stronger than that observed for high
      FFA, suggesting that adiponectin could be used as biomarker to identify subjects
      at high risk for T2DM and CAD.

PMID- 25849598
TI  - Expression of CDK1(Tyr15), pCDK1(Thr161), Cyclin B1 (total) and pCyclin
      B1(Ser126) in vulvar squamous cell carcinoma and their relations with
      clinicopatological features and prognosis.
AB  - Cyclin B1-CDK1 complex plays an important role in the regulation of cell cycle.
      Activation of Cyclin B1 and CDK1 and the formation of the complex in G2/M are
      under multiple regulations involving many regulators such as isoforms of 14-3-3
      and CDC25 and Wee1. Abnormal expression of Cyclin B1 and CDK1 has been detected
      in various tumors. However, to our knowledge no previous study has investigated
      Cyclin B1 and CDK1 in vulvar cancer. Therefore, we evaluated the statuses of
      CDK1Tyr15, pCDK1Thr161, Cyclin B1 (total) and pCyclin B1Ser126 in 297 cases of
      vulvar squamous cell carcinomas by immunohistochemistry. Statistical analyses
      were performed to explore their clinicopathological and prognostic values. In at
      least 25% of tumor cases high expression of CDK1Tyr15, pCDK1Thr161, Cyclin B1
      (total) and pCyclin B1Ser126 was observed, compared to the low levels in normal
      vulvar squamous epithelium. Elevated levels of CDK1Tyr15, pCDK1Thr161, Cyclin B1
      (total) and pCyclin B1Ser126 were correlated with advanced tumor behaviors and
      aggressive features. Although CDK1Tyr15, pCDK1Thr161, Cyclin B1 (total) and
      pCyclin B1Ser126 could not be identified as prognostic factors, combinations of
      (pCDK1Thr161 C+N + 14-3-3sigmaN), (pCDK1Thr161 C+N + 14-3-3etaC), (pCDK1Thr161
      C+N + Wee1C) and (pCDK1Thr161 C+N + 14-3-3sigmaN + 14-3-3etaC + Wee1C) were
      correlated with disease-specific survival (p = 0.036, p = 0.029, p = 0.042 and p
      = 0.007, respectively) in univariate analysis. The independent prognostic
      significance of (pCDK1Thr161 C+N + 14-3-3sigmaN + 14-3-3etaC + Wee1C) was
      confirmed by multivariate analysis. In conclusion, CDK1Tyr15, pCDK1Thr161, Cyclin
      B1 (total) and pCyclin B1Ser126 may be involved in progression of vulvar squamous
      cell carcinoma. The combination of pCDK1Thr161, 14-3-3sigma, 14-3-3eta and Wee1
      was a statistically independent prognostic factor. 

PMID- 25849599
TI  - Photoselective Vaporization of the Prostate for Benign Prostatic Hyperplasia
      Using the 180 Watt System: Multicenter Study of the Impact of Prostate Size on
      Safety and Outcomes.
AB  - PURPOSE: We evaluated photoselective vaporization of the prostate using the
      GreenLightTM XPSTM 180 W system for benign prostatic hyperplasia treatment in a
      large multi-institutional cohort at 2 years. We particularly examined safety,
      outcomes and the re-treatment rate in larger prostates, defined as a prostate
      volume of 80 cc or greater, to assess the potential of photoselective
      vaporization of the prostate as a size independent procedure. MATERIALS AND
      METHODS: A total of 1,196 patients were treated at 6 international centers in
      Canada, the United States, France and England. All parameters were collected
      retrospectively, including complications, I-PSS, maximum urinary flow rate, post
      void residual urine, prostate volume, prostate specific antigen and the
      endoscopic re-intervention rate. Subgroup stratified comparative analysis was
      performed according to preoperative prostate volume less than 80 vs 80 cc or
      greater on transrectal ultrasound. RESULTS: Median prostate size was 50 cc in 387
      patients and 108 cc in 741 in the prostate volume groups less than 80 and 80 cc
      or greater, respectively. The rate of conversion to transurethral prostate
      resection was significantly higher in the 80 cc or greater group than in the less
      than 80 cc group (8.4% vs 0.6%, p <0.01). I-PSS, quality of life score, maximum
      urinary flow rate and post-void residual urine were significantly improved
      compared to baseline at 6, 12 and 24 months of followup without significant
      differences between the prostate size groups. The re-treatment rate at 2 years
      reported in 5 of 411 patients was associated with the delivery of decreased
      energy density (2.1 vs 4.4 kJ/cc) in the group without re-treatment. CONCLUSIONS:
      Photoselective vaporization of the prostate using the XPS 180 W system is safe
      and efficacious, providing durable improvement in functional outcomes at 2 years
      independent of prostate size when treated with sufficient energy.

PMID- 25849600
TI  - Primary Endoscopic Realignment of Urethral Disruption Injuries--A Double-Edged
      Sword?
AB  - PURPOSE: Controversy remains regarding initial management of traumatic urethral
      disruption injuries. We evaluated the outcomes of primary endoscopic realignment
      vs suprapubic tube placement in this patient population. MATERIALS AND METHODS:
      We reviewed our urological trauma database for patients with blunt trauma related
      posterior urethral injuries from 2000 to 2014. Patients underwent primary
      endoscopic realignment or suprapubic tube placement alone. The primary outcome
      was the success of primary realignment, defined as no further need for urological
      intervention. Secondary outcomes were the need for endoscopic interventions
      and/or urethroplasty, time to urethroplasty, urethroplasty success and long-term
      functional outcomes. RESULTS: A total of 27 patients underwent primary
      realignment and 14 underwent suprapubic tube placement. Mean followup was 40
      months (median 24, range 1 to 152). Realignment was successful in 10 patients
      (37%) at a mean followup of 67.3 weeks (median 27.3, range 4 to 284). In the 17
      cases (63%) that failed mean time to failure was 9.7 weeks (median 8.5, range 1
      to 26). Seven patients (26%) treated with realignment and 11 (79%) with a
      suprapubic tube proceeded to urethroplasty. Mean +/- SD time to urethroplasty was
      significantly shorter in the suprapubic tube group (14.6 +/- 7.6 vs 5.8 +/- 1.6
      months, p = 0.003). There was no difference in operative time, complications,
      success or functional outcomes. CONCLUSIONS: Management of traumatic urethral
      disruption injuries by primary endoscopic realignment serves as definitive
      therapy in more than a third of treated patients. It prevents the need for formal
      urethroplasty in more than half of failed cases.

PMID- 25849601
TI  - The Effects of RAAS Inhibition in Rate Limiting Step by Aliskiren on Testicular
      Torsion Injury in Rats.
AB  - PURPOSE: Testicular torsion is a urological emergency. Failure of timely
      intervention for this issue leads the testicles to go into necrosis. If left
      untreated, it can lead to loss of the reproductive organs. The aim of this study
      was to examine the role of aliskiren in testicular torsion and detorsion
      injuries. MATERIALS AND METHODS: Rats were divided into 8 groups of 12 each,
      including no torsion-detorsion, no torsion-detorsion plus 200 mg/kg aliskiren
      orally, torsion, torsion-detorsion, torsion plus 100 mg/kg aliskiren orally,
      torsion plus 200 mg/kg aliskiren orally, torsion-detorsion plus 100 mg/kg
      aliskiren orally and torsion-detorsion plus 200 mg/kg aliskiren orally. Aliskiren
      was administered 30 minutes before ischemia and reperfusion, and also 24 hours
      before the experimental protocol in all treatment groups. Ischemia and
      reperfusion were each applied for 2 hours. RESULTS: Testicular damage decreased
      superoxide dismutase and glutathione, and increased malondialdehyde in the testis
      tissues of rats. Aliskiren administration increased superoxide dismutase and
      glutathione, and decreased malondialdehyde in the testis tissues. Values were
      measured by a biochemical autoanalyzer. In addition, this torsion-detorsion
      damage caused a significant increase in levels of the inflammatory cytokine and
      agents interleukin-1beta and inducible nitric oxide synthase, as examined by real
      time polymerase chain reaction. Aliskiren administration decreased these
      parameters. On pathological evaluation administration of a 200 mg/kg dose of
      aliskiren was found to protect the testis. Renin-angiotensin-aldosterone system
      inhibition by aliskiren caused an increase in serum renin levels and a decrease
      in serum angiotensin II levels. CONCLUSIONS: It appears that aliskiren protects
      the testis from ischemia-reperfusion damage by regulating inflammation and the
      oxidant-antioxidant balance via renin-angiotensin-aldosterone system inhibition.

PMID- 25849603
TI  - Trends in Toilet Training and Voiding Habits among Children with Down Syndrome.
AB  - PURPOSE: Children with Down syndrome are at risk for lower urinary tract
      dysfunction and delayed toilet training. Comparative studies regarding voiding
      function in the Down syndrome population are lacking. We assessed urinary
      continence and voiding function in patients with Down syndrome and a control
      group. MATERIALS AND METHODS: A questionnaire designed to assess toilet training,
      continence status, symptoms of lower urinary tract dysfunction and prior
      evaluation of urological complaints was sent to parents of 326 children with Down
      syndrome who had been seen at our institution previously. The same survey was
      administered to parents of patients without Down syndrome. Data were compiled,
      and descriptive and comparative statistical analyses were performed. RESULTS: A
      total of 77 patients comprised the Down syndrome group and 78 patients without
      Down syndrome comprised the control group. Average age of reported toilet
      training completion was 5.5 years in children with Down syndrome and 2.2 years in
      controls. Of children 5 years or older 79% with Down syndrome were toilet
      trained, compared to 100% of those without Down syndrome. Incontinence was
      reported in 46% of previously toilet trained children with Down syndrome and
      24.5% of controls. These findings were statistically significant. No significant
      difference was observed in the rate of urinary tract infection, symptoms of lower
      urinary tract dysfunction or evaluation for urological complaints. CONCLUSIONS:
      Children with Down syndrome can experience marked delay in toilet training and
      are more likely to suffer incontinence afterward. This study was ineffective in
      determining whether symptoms of lower urinary tract dysfunction could be related
      to decreased continence rates.

PMID- 25849602
TI  - Gleason 6 Prostate Cancer: Translating Biology into Population Health.
AB  - PURPOSE: Gleason 6 (3+3) is the most commonly diagnosed prostate cancer among men
      with prostate specific antigen screening, the most histologically well
      differentiated and is associated with the most favorable prognosis. Despite its
      prevalence, considerable debate exists regarding the genetic features, clinical
      significance, natural history, metastatic potential and optimal management.
      MATERIALS AND METHODS: Members of the Young Urologic Oncologists in the Society
      of Urologic Oncology cooperated in a comprehensive search of the peer reviewed
      English medical literature on Gleason 6 prostate cancer, specifically focusing on
      the history of the Gleason scoring system, histological features, clinical
      characteristics, practice patterns and outcomes. RESULTS: The Gleason scoring
      system was devised in the early 1960s, widely adopted by 1987 and revised in 2005
      with a more restrictive definition of Gleason 6 disease. There is near consensus
      that Gleason 6 meets pathological definitions of cancer, but controversy about
      whether it meets commonly accepted molecular and genetic criteria of cancer.
      Multiple clinical series suggest that the metastatic potential of contemporary
      Gleason 6 disease is negligible but not zero. Population based studies in the
      U.S. suggest that more than 90% of men newly diagnosed with prostate cancer
      undergo treatment and are exposed to the risk of morbidity for a cancer unlikely
      to cause symptoms or decrease life expectancy. Efforts have been proposed to
      minimize the number of men diagnosed with or treated for Gleason 6 prostate
      cancer. These include modifications to prostate specific antigen based screening
      strategies such as targeting high risk populations, decreasing the frequency of
      screening, recommending screening cessation, incorporating remaining life
      expectancy estimates, using shared decision making and novel biomarkers, and
      eliminating prostate specific antigen screening entirely. Large nonrandomized and
      randomized studies have shown that active surveillance is an effective management
      strategy for men with Gleason 6 disease. Active surveillance dramatically reduces
      the number of men undergoing treatment without apparent compromise of cancer
      related outcomes. CONCLUSIONS: The definition and clinical relevance of Gleason 6
      prostate cancer have changed substantially since its introduction nearly 50 years
      ago. A high proportion of screen detected cancers are Gleason 6 and the
      metastatic potential is negligible. Dramatically reducing the diagnosis and
      treatment of Gleason 6 disease is likely to have a favorable impact on the net
      benefit of prostate cancer screening.

PMID- 25849604
TI  - A systematic review of transitions between cigarette and smokeless tobacco
      product use in the United States.
AB  - BACKGROUND: Smokeless tobacco use is becoming an increasingly important public
      health issue in the US and may influence cigarette smoking behavior. Systematic
      information on transitions between smokeless tobacco and cigarette use in the US
      is limited. METHODS: We conducted a systematic review of published literature on
      transitions between smokeless tobacco and cigarette use in the US. We searched
      PubMed, Web of Science and EbscoHost databases for all published articles from
      January 2000 to March 2014 that presented estimates of transitions in US youth
      and adult study populations over time between at least one of the following
      tobacco use states: exclusive cigarette smoking, exclusive smokeless tobacco use,
      dual use of both products, and use of neither product. We excluded non-English
      language studies, studies published before 2000, clinical trials, controlled
      cessation programs, and clinical studies or evaluations of smokeless tobacco
      cessation programs. RESULTS: The review identified six studies on US populations
      published since 2000 with longitudinal data on some or all of the transitions
      that users can undergo between smokeless tobacco and cigarette use. There was
      considerable heterogeneity across studies in design and tobacco use definitions.
      Despite these differences, the existing data indicate that switching behaviors
      from exclusive smoking to exclusive smokeless tobacco use are limited (adults: 0%
      1.4%, adolescents: 0.8%-3.8%) but may be more common from exclusive smokeless
      tobacco use to exclusive smoking (adults: 0.9%-26.6%, adolescents: 16.6%-25.5%).
      Among adults, exclusive cigarette smoking was generally stable and consistent
      (79.7% to 87.6%) over follow-up across studies but less stable in adolescents
      (46.8%-78.7%). Exclusive smokeless tobacco use was less stable than exclusive
      cigarette smoking over time (adults: 59.4%-76.6%, adolescents: 26.2%-44.8%).
      CONCLUSION: This review provides published estimates of the proportions of adults
      and adolescents transitioning between tobacco use categories from the most
      recently available studies on longitudinal transitions between smokeless tobacco
      and cigarettes in the US. These data can be used to track tobacco use behaviors
      and evaluate their effect on public health; however, the data for these studies
      were generally collected more than a decade ago. Additional research including
      nationally representative longitudinal estimates using consistent definitions and
      designs, would improve understanding of current tobacco transition behaviors.

PMID- 25849606
TI  - Functional characterization of putative novel splicing mutations in the
      cardiomyopathy-causing genes.
AB  - Molecular diagnosis of cardiomyopathies remains difficult not only because of the
      large number of causative genes and the high rate of private mutations but also
      due to the large number of unclassified variants (UVs) found in patients' DNA.
      This study reports the functional splicing impact of nine novel genomic
      variations previously identified in unrelated patients with cardiomyopathies. To
      identify splice variants among these UVs, a combination of in silico and in vitro
      hybrid minigene tools was used as transcript is not available. Using this two
      step approach, these UVs were reclassified as splicing mutations (MYBPC3-c.655
      25A>G, MYBPC3-c.1790G>A (p.Arg597Gln), MYBPC3-c.2414-36G>T) or as mutations with
      a majority of abnormally spliced transcripts (MYBPC3-c.1182C>A, TNNT2-c.460G>A
      (p.Glu154Lys), and TNNT2-c.822-3C>A) or as variations with a weak splicing effect
      (TNNT2-c.1000-38C>A). For the two remaining variations in intron 11 of the TNNT2
      gene in the vicinity of the acceptor splice site (c.571-7G>A, c.571-29G>A), a
      minigene assay was inconclusive as exon 12 is neither recognized as an exon by
      HeLa nor by H9c2 cells. Our study highlights the importance of the combined use
      of in silico and in vitro splicing assays to improve the prediction of the
      functional splicing impact of identified genetic variants if the RNA sample from
      the patient is not easily available. 

PMID- 25849605
TI  - Radiological and pathological features associated with IDH1-R132H mutation status
      and early mortality in newly diagnosed anaplastic astrocytic tumours.
AB  - BACKGROUND: Glioblastoma can occur either de novo or by the transformation of a
      low grade tumour; the majority of which harbor a mutation in isocitrate
      dehydrogenase (IDH1). Anaplastic tumours are high-grade gliomas that may
      represent the final step in the evolution of a secondary glioblastoma or the
      initial presentation of an early primary glioblastoma. We sought to determine
      whether pathological and/or radiological variables exist that can reliably
      distinguish IDH1-R132H-positive from IDH1-R132H-negative tumours and to identify
      variables associated with early mortality. METHODS: Patients diagnosed with
      anaplastic astrocytic tumours were included. Magnetic resonance imaging was
      performed and immunohistochemistry was used to identify tumours with the IDH1
      R132H mutation. Survival was assessed 12 months after diagnosis. Variables
      associated with IDH1-R132H status were identified by univariate and ROC analysis.
      RESULTS: 37 gliomas were studied; 18 were positive for the IDH1-R132H mutation.
      No tumours demonstrated a combined loss of chromosomes 1p/19q. Patients with IDH1
      R132H-positive tumours were less likely to die within 12 months of diagnosis (17%
      vs. 47%; p=0.046), more likely to have tumours located in the frontal lobe (55%
      vs. 16%; p=0.015), and have a higher minimum apparent diffusion coefficient
      (1.115 x 10-3 mm2/sec vs. 0.838 x 10-3 mm2/sec; p=0.016), however, these
      variables demonstrated only moderate strength for predicting the IDH1-R132H
      mutation status (AUC=0.735 and 0.711, respectively). The Ki-67 index was
      significantly lower in IDH1-R132H-positive tumours (0.13 vs. 0.21; p=0.034). An
      increased risk of death was associated with contrast-enhancement >= 5 cm3 in
      patients with IDH1-R132H-positive tumours while edema >= 1 cm beyond the tumour
      margin and < 5 mitoses/mm2 were associated with an increased risk of death in
      patients with IDH1-R132H-negative tumours. CONCLUSIONS: IDH1-R132H-positive and 
      negative anaplastic tumours demonstrate unique features. Factors associated with
      early mortality are also dependent on IDH1-R132H status and can be used to
      identify patients at high risk for death.

PMID- 25849607
TI  - Change in and long-term investigation of neuro-otologic disorders in disaster
      stricken Fukushima prefecture: retrospective cohort study before and after the
      Great East Japan Earthquake.
AB  - On March 11, 2011, Japan's northeast Pacific coast was hit by a gigantic
      earthquake and subsequent tsunami. Soma City in Fukushima Prefecture is situated
      approximately 44 km north of Fukushima Daiichi Nuclear Power Plant. Soma General
      Hospital is the only hospital in Soma City that provides full-time
      otolaryngological medical care. We investigated the changes in new patients from
      one year before to three years after the disaster. We investigated 18,167 new
      patients treated at our department during the four years from April 1, 2010 to
      March 31, 2014. Of the new patients, we categorized the diagnoses into Meniere's
      disease, acute low-tone sensorineural hearing loss, vertigo, sudden deafness,
      tinnitus, and facial palsy as neuro-otologic symptoms. We also investigated the
      changes in the numbers of patients whom we examined at that time concerning other
      otolaryngological disorders, including epistaxis, infectious diseases of the
      laryngopharynx, and allergic rhinitis. The total number of new patients did not
      change remarkably on a year-to-year basis. Conversely, cases of vertigo,
      Meniere's disease, and acute low-tone sensorineural hearing loss increased in
      number immediately after the disaster, reaching a plateau in the second year and
      slightly decreasing in the third year. Specifically, 4.8% of patients suffering
      from these neuro-otologic diseases had complications from depression and other
      mental diseases. With regard to new patients in our department, there was no
      apparent increase in the number of patients suffering from diseases other than
      neuro-otologic diseases, including epistaxis, and allergic rhinitis. Patients
      suffering from vertigo and/or dizziness increased during the first few years
      after the disaster. These results are attributed to the continuing stress and
      tension of the inhabitants. This investigation of those living in the disaster
      area highlights the need for long-term support. 

PMID- 25849608
TI  - Metal ion-directed dynamic splicing of DNA through global conformational change
      by intramolecular complexation.
AB  - Chemically engineered DNAs-in which global conformation can be modulated in
      response to specific stimuli-could be allosteric functional DNAs themselves or
      work as a modulator of the functional nucleic acids such as DNAzymes and
      aptamers. Here, we show that two terpyridines built in the DNA backbone form a
      stable intramolecular 1:2 complex, [M(terpy)2](2+), with divalent transition
      metal ions. Upon complexation, the DNA conjugates adopt a Omega-shape structure,
      in which two distal sequences located outside the terpyridines connect with each
      other to form a continuous segment with a specific structure or sequence. Such a
      DNA structure is globally controlled by local metal complexation events that can
      be rationally designed based on general coordination chemistry. This method is
      regarded as metal ion-directed dynamic sequence edition or DNA splicing. DNAzymes
      with peroxidase-like activity can thus be regulated by several transition metal
      ions through sequence edition techniques based on the Omega-motif.

PMID- 25849609
TI  - Camellia sinensis in asymptomatic hyperuricemia: A meta-analysis of tea or tea
      extract effects on uric acid levels.
AB  - Flavanols of Camellia sinensis exhibit uric acid (UA) lowering effect, through
      the modulation of both xanthine oxidase and urate excretion. In order to
      investigate the potential benefit of Camellia Sinenis products in asymptomatic
      hyperuricemia, a meta-analysis of long-term Randomized Controlled Trials (RCT)
      with tea or tea extract has been conducted. From 20 human intervention studies
      selected only 5 RCT (13 interventions) were suitable for meta-analysis (n = 472).
      The current "normal" range set for hyperuricemia fails to identify patients with
      potential metabolic disorders. Therefore on the basis of the literature data, we
      fixed cut-off limits for UA baseline levels of 4.5 mg/dl for women, 6.1 mg/dl for
      men, and 5.5 mg/dl for studies involving mixed populations. Statistically
      significant effects were not found, but subgroup analysis revealed that the
      Pooled Estimate effect was different in subjects with baseline levels under [MD
      (95% CI): 0.1078 (-0.0528 to 0.2684)] and over the cut-off [MD (95% CI): -0.0239
      (0.3311 to 0.2833)]. However, due to the low number of RCT and to the lack of
      data on bioavailability, it is difficult to draw any firm conclusion and more
      studies are needed to establish if tea flavanols could be useful in asymptomatic
      hyperuricemia treatment.

PMID- 25849610
TI  - Planar Mn4O cluster homochiral metal-organic framework for HPLC separation of
      pharmaceutically important (+/-)-ibuprofen racemate.
AB  - A planar tetracoordinated oxygen containing a homochiral metal-organic framework
      (MOF) has been synthesized and characterized that can be used as a new chiral
      stationary phase in high-performance liquid chromatography to efficiently
      separate racemates such as pharmaceutically important (+/-)-ibuprofen and (+/-)-1
      phenyl-1,2-ethanediol. 

PMID- 25849611
TI  - Typhoid fever in young children in Bangladesh: clinical findings, antibiotic
      susceptibility pattern and immune responses.
AB  - BACKGROUND: Children bear a large burden of typhoid fever caused by Salmonella
      enterica serotype Typhi (S. Typhi) in endemic areas. However, immune responses
      and clinical findings in children are not well defined. Here, we describe
      clinical and immunological characteristics of young children with S. Typhi
      bacteremia, and antimicrobial susceptibility patterns of isolated strains.
      METHODS: As a marker of recent infection, we have previously characterized
      antibody-in-lymphocyte secretion (TPTest) during acute typhoid fever in adults.
      We similarly assessed membrane preparation (MP) IgA responses in young children
      at clinical presentation, and then 7-10 days and 21-28 days later. We also
      assessed plasma IgA, IgG and IgM responses and T cell proliferation responses to
      MP at these time points. We compared responses in young children (1-5 years) with
      those seen in older children (6-17 years), adults (18-59 years), and age-matched
      healthy controls. PRINCIPAL FINDINGS: We found that, compared to age-matched
      controls patients in all age cohorts had significantly more MP-IgA responses in
      lymphocyte secretion at clinical presentation, and the values fell in all groups
      by late convalescence. Similarly, plasma IgA responses in patients were elevated
      at presentation compared to controls, with acute and convalescent IgA and IgG
      responses being highest in adults. T cell proliferative responses increased in
      all age cohorts by late convalescence. Clinical characteristics were similar in
      all age cohorts, although younger children were more likely to present with loss
      of appetite, less likely to complain of headache compared to older cohorts, and
      adults were more likely to have ingested antibiotics. Multi-drug resistant
      strains were present in approximately 15% of each age cohort, and 97% strains had
      resistance to nalidixic acid. CONCLUSIONS: This study demonstrates that S. Typhi
      bacteremia is associated with comparable clinical courses, immunologic responses
      in various age cohorts, including in young children, and that TPTest can be used
      as marker of recent typhoid fever, even in young children.

PMID- 25849612
TI  - Peroxynitrite decomposition catalyst prevents matrix metalloproteinase-9
      activation and neurovascular injury after hemoglobin injection into the caudate
      nucleus of rats.
AB  - Hemoglobin (Hb) is a major constituent of blood and a potent mediator of
      oxidative or nitrative stress after intracerebral hemorrhage (ICH). Our previous
      study demonstrated that Hb could induce abundant peroxynitrite (ONOO(-))
      formation in vivo, which may be involved in the blood-brain barrier (BBB)
      disruption, however, the drug intervention is absent and also the underlying
      mechanism. Using an experimental stroke model by injecting Hb into the caudate
      nucleus of male Sprague-Dawley rats, we assessed the role of ONOO(-)
      decomposition catalyst, 5,10,15,20-tetrakis (4-sulfonatophenyl) porphyrinato
      iron(III) [FeTPPS] in the activation of MMP-9 and Hb-induced neurovascular
      injuries. 3-Nitrotyrosine (3-NT, as an index of ONOO(-) formation) and NF-kappaB
      expression was measured by western blot (WB) and immunohistochemistry
      (IHC)/immunofluorescence (IF). Activity of MMP was evaluated by in situ
      zymography. Neurovascular injury was assessed using zonula occludens-1 (ZO-1) by
      WB and IF, fibronectin (FN) and neuron-specific nuclear protein (NeuN) IHC.
      Perihematomal cell death was determined by TUNEL assay. Behavioral outcome was
      measured by modified neurological severity score (mNSS) test. At the injured
      striata, profuse 3-NT was produced and mainly expressed in neutrophils and
      microglia/macrophages. 3-NT formation significantly colocalized with nuclear
      factor-kappaB (NF-kappaB) expression. In situ zymography showed that gelatinase
      activity was mostly co-localized with neurons and blood vessel walls and partly
      with neutrophils and microglia/macrophages. Enhanced 3-NT production, NF-kappaB
      induction and MMP-9 activation were obviously reduced after FeTPPS treatment. Hb
      induced injury to tight junction protein (ZO-1), basal lamina of FN
      immunopositive microvasculature and neural cells was evidently ameliorated by
      FeTPPS. In addition, apoptotic cell numbers as well as behavioral deficits were
      also improved. The present study shows that the administration of the ONOO(-)
      decomposition catalyst FeTPPS protects against Hb-induced neurovascular injuries
      and improves neurological function, which possibly in part by suppressing MMP-9
      activation. 

PMID- 25849613
TI  - Effect of mental fatigue on speed-accuracy trade-off.
AB  - The aim of this study was to investigate the effects of mental fatigue on the
      duration of actual and imagined goal-directed arm movements involving speed
      accuracy trade-off. Ten participants performed actual and imagined point-to-point
      arm movements as accurately and as fast as possible, before and after a 90-min
      sustained cognitive task inducing mental fatigue, and before and after viewing a
      neutral control task (documentary movie) that did not induce mental fatigue.
      Target width and center-to-center target distance were varied, resulting in five
      different indexes of difficulty. Prior to mental fatigue, actual and imagined
      movement duration increased with the difficulty of the task, as predicted by
      Fitts' law. Mental fatigue task induced a 4.1+/-0.7% increase in actual movement
      duration and a 9.6+/-1.1% increase in imagined movement duration, independently
      of the index of difficulty. The trial-by-trial evolution of actual and imagined
      movement duration remained stable with mental fatigue. The control task did not
      induce any change in actual and imagined movement duration. The results suggested
      that movement was slowed in the presence of mental fatigue, maybe due to
      proactive changes occurring during the preparatory state of the movement, to
      preserve task success. 

PMID- 25849614
TI  - Neurochemical and electrophysiological deficits in the ventral hippocampus and
      selective behavioral alterations caused by high-fat diet in female C57BL/6 mice.
AB  - Mounting experimental evidence, predominantly from male rodents, demonstrates
      that high-fat diet (HFD) consumption and ensuing obesity are detrimental to the
      brain. To shed additional light on the neurological consequences of HFD
      consumption in female rodents and to determine the relatively early impact of HFD
      in the likely continuum of neurological dysfunction in the context of chronic HFD
      intake, this study investigated effects of HFD feeding for up to 12weeks on
      selected behavioral, neurochemical, and electrophysiological parameters in adult
      female C57BL/6 mice; particular focus was placed on the ventral hippocampus
      (vHIP). Selected locomotor, emotional and cognitive functions were evaluated
      using behavioral tests after 5weeks on HFD or control (low-fat diet) diets. One
      week later, mice were sacrificed and brain regional neurochemical (monoamine)
      analysis was performed. Behaviorally naive mice were maintained on their
      respective diets for an additional 5-6weeks at which time synaptic plasticity was
      determined in ex vivo slices from the vHIP. HFD-fed female mice exhibited
      increased: (i) locomotor activity in the open field testing, (ii) mean turn time
      on the pole test, (iii) swimming time in the forced swim test, and (iv) number of
      marbles buried in the marble burying test. In contrast, the novel object
      recognition memory was unaffected. Mice on HFD also had decreased norepinephrine
      and dopamine turnover, respectively, in the prefrontal cortex and the vHIP. HFD
      consumption for a total of 11-12weeks altered vHIP synaptic plasticity, evidenced
      by significant reductions in the paired-pulse ratio and long-term potentiation
      (LTP) magnitude. In summary, in female mice, HFD intake for several weeks induced
      multiple behavioral alterations of mainly anxiety-like nature and impaired
      monoamine pathways in a brain region-specific manner, suggesting that in the
      female, certain behavioral domains (anxiety) and associated brain regions, i.e.,
      the vHIP, are preferentially targeted by HFD. 

PMID- 25849616
TI  - An ANNEXIN-like protein from the cereal cyst nematode Heterodera avenae
      suppresses plant defense.
AB  - Parasitism genes encoding secreted effector proteins of plant-parasitic nematodes
      play important roles in facilitating parasitism. An annexin-like gene was
      isolated from the cereal cyst nematode Heterodera avenae (termed Ha-annexin) and
      had high similarity to annexin 2, which encodes a secreted protein of Globodera
      pallida. Ha-annexin encodes a predicted 326 amino acid protein containing four
      conserved annexin domains. Southern blotting revealed that there are at least two
      homologies in the H. avenae genome. Ha-annexin transcripts were expressed within
      the subventral gland cells of the pre-parasitic second-stage juveniles by in situ
      hybridization. Additionally, expression of these transcripts were relatively
      higher in the parasitic second-stage juveniles by quantitative real-time RT-PCR
      analysis, coinciding with the time when feeding cell formation is initiated.
      Knockdown of Ha-annexin by method of barley stripe mosaic virus-based host
      induced gene silencing (BSMV-HIGS) caused impaired nematode infections at 7 dpi
      and reduced females at 40 dpi, indicating important roles of the gene in
      parasitism at least in early stage in vivo. Transiently expression of Ha-ANNEXIN
      in onion epidermal cells and Nicotiana benthamiana leaf cells showed the whole
      cell-localization. Using transient expression assays in N. benthamiana, we found
      that Ha-ANNEXIN could suppress programmed cell death triggered by the pro
      apoptotic mouse protein BAX and the induction of marker genes of PAMP-triggered
      immunity (PTI) in N. benthamiana. In addition, Ha-ANNEXIN targeted a point in the
      mitogen-activated protein kinase (MAPK) signaling pathway downstream of two
      kinases MKK1 and NPK1 in N. benthamiana. 

PMID- 25849615
TI  - The role of TRPM2 in hydrogen peroxide-induced expression of inflammatory
      cytokine and chemokine in rat trigeminal ganglia.
AB  - Trigeminal ganglia (TG) contain neuronal cell bodies surrounded by satellite
      glial cells. Although peripheral injury is well known to induce changes in gene
      expression within sensory ganglia, detailed mechanisms whereby peripheral injury
      leads to gene expression within sensory ganglia are not completely understood.
      Reactive oxygen species (ROS) are an important modulator of hyperalgesia, but the
      role of ROS generated within sensory ganglia is unclear. Since ROS are known to
      affect transcription processes, ROS generated within sensory ganglia could
      directly influence gene expression and induce cellular changes at the soma level.
      In this study, we hypothesized that peripheral inflammation leads to cytokine and
      chemokine production and ROS generation within TG and that transient receptor
      potential melastatin (TRPM2), a well known oxidative sensor, contributes to ROS
      induced gene regulation within TG. The masseter injection of complete Freund's
      adjuvant (CFA) resulted in a significantly elevated level of ROS within TG of the
      inflamed side with a concurrent increase in cytokine expression in TG. Treatment
      of TG cultures with H2O2 significantly up-regulated mRNA and protein levels of
      cytokine/chemokine such as interleukin 6 (IL-6) and chemokine (C-X-C motif)
      ligand 2 (CXCL2). TRPM2 was expressed in both neurons and non-neuronal cells in
      TG, and pretreatment of TG cultures with 2-aminoethoxydiphenyl borate (2-APB), an
      inhibitor of TRPM2, or siRNA against TRPM2 attenuated H2O2-induced up-regulation
      of IL-6 and CXCL2. These results suggested that activation of TRPM2 could play an
      important role in the modulation of cytokine/chemokine expression within TG under
      oxidative stress and that such changes may contribute to amplification of
      nociceptive signals leading to pathological pain conditions. 

PMID- 25849618
TI  - Artificial miRNAs Targeting Mutant Huntingtin Show Preferential Silencing In
      Vitro and In Vivo.
AB  - Huntington's disease (HD) is a dominantly inherited neurodegenerative disease
      caused by CAG repeat expansion in exon 1 of huntingtin (HTT). Studies in mouse
      models of HD with a regulated mutant transgene show that continuous mutant allele
      expression is required for behavioral and pathological signs; when mutant HTT
      expression declined, neuronal degeneration improved. To date, it is unknown
      whether neural cells in the adult human brain can tolerate reduction in both
      normal and mutant alleles. Thus, it may be important to develop allele-specific
      silencing approaches. Several siRNA sequences targeting the CAG expanded motif or
      prevalent single-nucleotide polymorphisms (SNPs) in linkage disequilibrium with
      the mutant allele have been designed and their selectivity demonstrated in vitro.
      However, it is unknown whether these allele-specific siRNAs will retain their
      specificity when expressed from artificial RNAi platforms. Here, we designed CAG-
      and SNP- targeting artificial miRNAs and demonstrate that some, but not all,
      retained their selectivity in vitro using an allele-specific reporter system and
      in vivo in a transgenic mouse model developed to express normal and mutant human
      HTT alleles. 

PMID- 25849617
TI  - Predictors of rational management of diarrhea in an endemic setting: observation
      from India.
AB  - BACKGROUND: Decades after the establishment of clear guidelines for management,
      mostly due to irrational approach, diarrhea is still a major concern in the
      developing world, including India. The scenario is even worse in urban slums
      owing to poor health-seeking and socio-environmental vulnerability. Determining
      the distribution of rational diarrhea management by practitioners and
      identification of its important predictors seemed urgent to minimize the
      potential for antibiotic resistance, diarrhea-related mortality and morbidity in
      these areas. METHODS: Between May 2011 and January 2012, 264 consenting, randomly
      selected qualified and non-qualified practitioners (including pharmacists) were
      interviewed in the slums of Kolkata, a populous city in eastern India, regarding
      their characteristics, diarrhea-related knowledge (overall and in six separate
      domains: signs/symptoms, occurrence/spread, management, prevention/control,
      cholera and ORS), prescribed antibiotics, intravenous fluid (IVF) and laboratory
      investigations. Rationality was established based on standard textbooks. RESULTS:
      Among participants, 53.03% had no medical qualifications, 6.06% were attached to
      Governmental hospitals, 19.32% had best knowledge regarding diarrhea. While
      treating diarrhea, 7.20%, 17.80% and 20.08% respectively advised antibiotics, IVF
      and laboratory tests rationally. Logistic regression revealed that qualified and
      Governmental-sector practitioners managed diarrhea more rationally. Having best
      diarrhea-related knowledge regarding signs/symptoms (OR=5.49, p value=0.020),
      occurrence/spread (OR=3.26, p value=0.035) and overall (OR=6.82, p value=0.006)
      were associated with rational antibiotic prescription. Rational IVF
      administration was associated with best knowledge regarding diarrheal
      signs/symptoms (OR=3.00, p value=0.017), occurrence/spread (OR=3.57, p
      value=0.004), prevention/control (OR=4.89, p value=0.037), ORS (OR=2.55, p
      value=0.029) and overall (OR=4.57, p value<0.001). Best overall (OR=2.68, p
      value=0.020) and cholera-related knowledge (OR=2.34, p value=0.019) were
      associated with rational laboratory testing strategy. CONCLUSION: Diarrheal
      management practices were unsatisfactory in urban slums where practitioners'
      knowledge was a strong predictor for rational management. Interventions targeting
      non-qualified, independent practitioners to improve their diarrhea-related
      knowledge seemed to be required urgently to ensure efficient management of
      diarrhea in these endemic settings.

PMID- 25849619
TI  - Non-homogeneous fractal hierarchical weighted networks.
AB  - A model of fractal hierarchical structures that share the property of non
      homogeneous weighted networks is introduced. These networks can be completely and
      analytically characterized in terms of the involved parameters, i.e., the size of
      the original graph Nk and the non-homogeneous weight scaling factors r1, r2, . .
      . rM. We also study the average weighted shortest path (AWSP), the average degree
      and the average node strength, taking place on the non-homogeneous hierarchical
      weighted networks. Moreover the AWSP is scrupulously calculated. We show that the
      AWSP depends on the number of copies and the sum of all non-homogeneous weight
      scaling factors in the infinite network order limit. 

PMID- 25849620
TI  - Elevational distribution and extinction risk in birds.
AB  - Mountainous regions are hotspots of terrestrial biodiversity. Unlike islands,
      which have been the focus of extensive research on extinction dynamics, fewer
      studies have examined mountain ranges even though they face increasing threats
      from human pressures - notably habitat conversion and climate change. Limits to
      the taxonomic and geographical extent and resolution of previously available
      information have precluded an explicit assessment of the relative role of
      elevational distribution in determining extinction risk. We use a new global
      species-level avian database to quantify the influence of elevational
      distribution (range, maximum and midpoint) on extinction risk in birds at the
      global scale. We also tested this relationship within biogeographic realms,
      higher taxonomic levels, and across phylogenetic contrasts. Potential confounding
      variables (i.e. phylogenetic, distributional, morphological, life history and
      niche breadth) were also tested and controlled for. We show that the three
      measures of elevational distribution are strong negative predictors of avian
      extinction risk, with elevational range comparable and complementary to that of
      geographical range size. Extinction risk was also found to be positively
      associated with body weight, development and adult survival, but negatively
      associated with reproduction and niche breadth. The robust and consistent
      findings from this study demonstrate the importance of elevational distribution
      as a key driver of variation in extinction dynamics in birds. Our results also
      highlight elevational distribution as a missing criterion in current schemes for
      quantifying extinction risk and setting species conservation priorities in birds.
      Further research is recommended to test for generality across non-avian taxa,
      which will require an advance in our knowledge of species' current elevational
      ranges and increased efforts to digitise and centralise such data. 

PMID- 25849621
TI  - Dysregulation of microRNAs in breast cancer and their potential role as
      prognostic and predictive biomarkers in patient management.
AB  - MicroRNAs (miRNAs) are an emerging class of gene expression modulators with
      relevant roles in several biological processes, including cell differentiation,
      development, apoptosis, and regulation of the cell cycle. Deregulation of those
      tiny RNA molecules has been described frequently as a major determinant for the
      initiation and progression of diseases, including cancer. Not only miRNAs but
      also the enzymes responsible for miRNA processing could be deregulated in cancer.
      In this review, we address the role of miRNAs in the pathogenesis of breast
      cancer, since there are oncogenic, tumor-suppressive, and metastatic-influencing
      miRNAs. Additionally, the different detection platforms and normalization
      strategies for miRNAs will be discussed. The major part of this review, however,
      will focus on the capability of miRNAs to act as diagnostic, predictive, or
      prognostic biomarkers. We will give an overview of their potential to correlate
      with response to or benefit from a given treatment and we will consider their
      ability to give information on prognosis in breast cancer. We will focus on
      miRNAs validated by more than one study or verified in independent cohorts or
      where results rely on preclinical as well as clinical evidence. As such, we will
      discuss their potential use in the personalized management of breast cancer. 

PMID- 25849622
TI  - Regulation of IL-17A responses in human airway smooth muscle cells by Oncostatin
      M.
AB  - BACKGROUND: Regulation of human airway smooth muscle cells (HASMC) by cytokines
      contributes to chemotactic factor levels and thus to inflammatory cell
      accumulation in lung diseases. Cytokines such as the gp130 family member
      Oncostatin M (OSM) can act synergistically with Th2 cytokines (IL-4 and IL-13) to
      modulate lung cells, however whether IL-17A responses by HASMC can be altered is
      not known. OBJECTIVE: To determine the effects of recombinant OSM, or other gp130
      cytokines (LIF, IL-31, and IL-6) in regulating HASMC responses to IL-17A,
      assessing MCP-1/CCL2 and IL-6 expression and cell signaling pathways. METHODS:
      Cell responses of primary HASMC cultures were measured by the assessment of
      protein levels in supernatants (ELISA) and mRNA levels (qRT-PCR) in cell
      extracts. Activation of STAT, MAPK (p38) and Akt pathways were measured by
      immunoblot. Pharmacological agents were used to assess the effects of inhibition
      of these pathways. RESULTS: OSM but not LIF, IL-31 or IL-6 could induce
      detectable responses in HASMC, elevating MCP-1/CCL2, IL-6 levels and activation
      of STAT-1, 3, 5, p38 and Akt cell signaling pathways. OSM induced synergistic
      action with IL-17A enhancing MCP-1/CCL-2 and IL-6 mRNA and protein expression,
      but not eotaxin-1 expression, while OSM in combination with IL-4 or IL-13
      synergistically induced eotaxin-1 and MCP-1/CCL2. OSM elevated steady state mRNA
      levels of IL-4Ralpha, OSMRbeta and gp130, but not IL-17RA or IL-17RC.
      Pharmacologic inhibition of STAT3 activation using Stattic down-regulated OSM,
      OSM/IL-4 or OSM/IL-13, and OSM/IL-17A synergistic responses of MCP-1/CCL-2
      induction, whereas, inhibitors of Akt and p38 MAPK resulted in less reduction in
      MCP-1/CCL2 levels. IL-6 expression was more sensitive to inhibition of p38 (using
      SB203580) and was affected by Stattic in response to IL-17A/OSM stimulation.
      CONCLUSIONS: Oncostatin M can regulate HASMC responses alone or in synergy with
      IL-17A. OSM/IL-17A combinations enhance MCP-1/CCL2 and IL-6 but not eotaxin-1.
      Thus, OSM through STAT3 activation of HASMC may participate in inflammatory cell
      recruitment in inflammatory airway disease.

PMID- 25849624
TI  - Correction: bony healing of unstable thoracolumbar burst fractures in the elderly
      using percutaneously applied titanium mesh cages and a transpedicular fixation
      system with expandable screws.

PMID- 25849623
TI  - Social functioning trajectories of young first-episode psychosis patients with
      and without cannabis misuse: a 30-month follow-up study.
AB  - The aim of the study was to investigate trajectories of social functioning in
      young people with first-episode psychosis (FEP) with and without cannabis misuse
      using a secondary analysis of data from the Episode-II trial. Forty-two young
      people with FEP and comorbid cannabis use disorder were compared with 39 young
      people with FEP but without a cannabis use disorder. Social functioning was
      assessed every 6 months during a 30-month follow-up. Multilevel linear growth
      curve modeling was used to compare the social functioning trajectories over time
      for those with and without cannabis misuse. Cannabis misuse was not associated
      with social functioning at baseline assessment. Over a 30-month follow-up, FEP
      patients without cannabis disorder showed significant improvements in their
      social functioning, whereas patients with cannabis misuse at baseline displayed
      no such improvement. Patients with and without cannabis misuse differed
      significantly in their levels of social functioning after 24 months. Similar
      results were obtained after adjusting for potential confounders (i.e., age,
      gender, negative symptoms, premorbid functioning, DSM-IV diagnoses, baseline
      social functioning and other substance use). In the context of a specialized
      early intervention service, patients with cannabis misuse at baseline did not
      attain the improvements in social outcomes observed in their counterparts without
      cannabis misuse. There is a need to develop effective interventions to reduce
      cannabis misuse to ultimately improve social outcomes in young people with
      psychosis. 

PMID- 25849625
TI  - Pilot Study on the Effect of Botanical Medicine (Tribulus terrestris) on Serum
      Testosterone Level and Erectile Function in Aging Males With Partial Androgen
      Deficiency (PADAM).
AB  - This study was conducted on 30 consecutive male patients presenting to Kasr-Al
      Ainy Andrology outpatient clinic complaining of manifestations of partial
      androgen deficiency in aging males (PADAM). In this study (750 mg/day) of
      Tribulus terrestris in 3 divided doses, each of 250 mg, as an endogenous
      testosterone enhancer had been tried for a duration of 3 months and the
      evaluation of its effect had been monitored for each patient concerning its
      effect on serum testosterone (total and free) and luteinizing hormone (LH), as
      well as its impact on erectile function, which was evaluated by the International
      Index of Erectile Function-5 (IIEF-5) questionnaire for those patients. Results
      showed a statistically significant difference in the level of testosterone (total
      and free) and IIEF-5, but no statistically significant difference in the level of
      LH before and after treatment. Also, the study showed statistically significant
      correlation between testosterone (total and free) and IIEF-5, but no
      statistically significant correlation between the level of LH and the IIEF-5
      before and after treatment. 

PMID- 25849626
TI  - Poly(amidoamine) Dendrimers with Carbonic Anhydrase Inhibitory Activity and
      Antiglaucoma Action.
AB  - Four generations of poly(amidoamine) (PAMAM) dendrimers decorated with
      benzenesulfonamide moieties were prepared by derivatizing the amino groups of the
      dendrimer with 4-carboxy-benzenesulfonamide functionalities. Compounds
      incorporating 4, 8, 16, and 32 sulfonamide moieties were thus obtained, which
      showed an increasing carbonic anhydrase (CA, EC 4.2.1.1) inhibitory action with
      the increase of the number of sulfamoyl groups in the dendrimer. Best inhibitory
      activity (in the low nanomolar-subnanomolar range) was observed for isoforms CA
      II and XII, involved among others in glaucoma. In an animal model of this
      disease, the chronic administration of such dendrimers for 5 days led to a much
      more efficient drop of intraocular pressure compared to the standard drug
      dorzolamide. 

PMID- 25849627
TI  - A randomized trial comparing the diagnostic accuracy of visual inspection with
      acetic acid to Visual Inspection with Lugol's Iodine for cervical cancer
      screening in HIV-infected women.
AB  - Visual inspection with Acetic Acid (VIA) and Visual Inspection with Lugol's
      Iodine (VILI) are increasingly recommended in various cervical cancer screening
      protocols in low-resource settings. Although VIA is more widely used, VILI has
      been advocated as an easier and more specific screening test. VILI has not been
      well-validated as a stand-alone screening test, compared to VIA or validated for
      use in HIV-infected women. We carried out a randomized clinical trial to compare
      the diagnostic accuracy of VIA and VILI among HIV-infected women. Women attending
      the Family AIDS Care and Education Services (FACES) clinic in western Kenya were
      enrolled and randomized to undergo either VIA or VILI with colposcopy. Lesions
      suspicious for cervical intraepithelial neoplasia 2 or greater (CIN2+) were
      biopsied. Between October 2011 and June 2012, 654 were randomized to undergo VIA
      or VILI. The test positivity rates were 26.2% for VIA and 30.6% for VILI (p =
      0.22). The rate of detection of CIN2+ was 7.7% in the VIA arm and 11.5% in the
      VILI arm (p = 0.10). There was no significant difference in the diagnostic
      performance of VIA and VILI for the detection of CIN2+. Sensitivity and
      specificity were 84.0% and 78.6%, respectively, for VIA and 84.2% and 76.4% for
      VILI. The positive and negative predictive values were 24.7% and 98.3% for VIA,
      and 31.7% and 97.4% for VILI. Among women with CD4+ count < 350, VILI had a
      significantly decreased specificity (66.2%) compared to VIA in the same group
      (83.9%, p = 0.02) and compared to VILI performed among women with CD4+ count >=
      350 (79.7%, p = 0.02). VIA and VILI had similar diagnostic accuracy and rates of
      CIN2+ detection among HIV-infected women.

PMID- 25849628
TI  - A humanized leucine zipper-TRAIL hybrid induces apoptosis of tumors both in vitro
      and in vivo.
AB  - Evidence suggests that stimulating apoptosis in malignant cells without
      inflicting collateral damage to the host's normal tissues is a promising cancer
      therapy. Chemo- and radiation therapies that, especially if combined, induce
      apoptosis in tumor cells have been used for treating cancer patients for decades.
      These treatments, however, are limited in their ability to discriminate between
      malignant and non-malignant cells and, therefore, produce substantial healthy
      tissue damage and subsequent toxic side-effects. In addition, as a result of
      these therapies, many tumor types acquire an apoptosis-resistant phenotype and
      become more aggressive and metastatic. Tumor necrosis factor-Related Apoptosis
      Inducing Ligand (TRAIL) has been considered a promising and reliable selective
      inducer of apoptosis in cancerous cells. TRAIL, however, is not uniformly
      effective in cancer and multiple cancer cell types are considered resistant to
      natural TRAIL. To overcome this deficiency of TRAIL, we have earlier constructed
      a yeast-human hybrid leucine zipper-TRAIL in which the yeast GCN4-pII leucine
      zipper was fused to human TRAIL (GCN4-TRAIL). This construct exhibited a
      significantly improved anti-tumor apoptotic activity and safety, but is
      potentially immunogenic in humans. Here, we report a novel, potent, and fully
      human ATF7 leucine zipper-TRAIL (ATF7-TRAIL) fusion construct that is expected to
      have substantially lower immunogenicity. In solution, ATF7-TRAIL exists solely as
      a trimer with a Tm of 80 degrees C and is active against cancer cells both in
      vitro and in vivo, in a mouse tumor xenograft model. Our data suggest that our re
      engineered TRAIL is a promising candidate for further evaluation as an antitumor
      agent. 

PMID- 25849629
TI  - Comparison of caudal and pre-scrotal castration for management of perineal hernia
      in dogs between 2004 and 2014.
AB  - AIMS: To compare peri- and post-operative complications associated with caudal
      scrotal castration (CSC) and perineal hernia repair with pre-scrotal castration
      (PSC) in conjunction with another surgical procedure. METHODS: Medical records
      were reviewed for 51 intact male dogs that were admitted to the Veterinary
      Emergency and Surgical Center, Levittown, PA, and underwent a CSC and perineal
      hernia repair using an internal obturator muscle flap (IOMF) between 2004 and
      2014. Perioperative, and major and minor post-operative complications noted
      within the 2 week follow up period were reported and compared to 91 intact male
      dogs that underwent a PSC in conjunction with a second surgical procedure.
      RESULTS: There were no recorded perioperative or major post-operative
      complications in either group. There were 3/51 (6%) minor post-operative
      complications in the CSC group compared to 6/91 (7%) in the PSC group. There were
      2/51 (4%) and 4/91 (4%) cases that developed heat, erythema and swelling
      associated with the incision site and 1/51 (2%) and 2/91 (2%) cases that
      developed scrotal swelling in the CSC and PSC groups, respectively. Overall,
      there was no difference in the prevalence of minor complications between the two
      groups (p=0.86). CONCLUSIONS AND CLINICAL RELEVANCE: Caudal scrotal castration
      was not associated with more perioperative or postoperative complications
      relative to PSC. Utilising the CSC approach eliminates the need to aseptically
      prepare and drape a second site when carrying out perineal hernia repair, as well
      as the need for patient repositioning. Thus, we recommend that CSC be the
      preferred surgical technique when performing orchiectomy in dogs concurrent with
      perineal hernia repair.

PMID- 25849631
TI  - Smarter than others? Conjectures in lowest unique bid auctions.
AB  - Research concerning various types of auctions, such as English auctions, Dutch
      auctions, highest-price sealed-bid auctions, and second-price sealed-bid
      auctions, is always a topic of considerable interest in interdisciplinary fields.
      The type of auction, known as a lowest unique bid auction (LUBA), has also
      attracted significant attention. Various models have been proposed, but they
      often fail to explain satisfactorily the real bid-distribution characteristics.
      This paper discusses LUBA bid-distribution characteristics, including the
      inverted-J shape and the exponential decrease in the upper region. The authors
      note that this type of distribution, which initially increases and later
      decreases, cannot be derived from the symmetric Nash equilibrium framework based
      on perfect information that has previously been used. A novel optimization model
      based on non-perfect information is presented. The kernel of this model is the
      premise that agents make decisions to achieve maximum profit based on imaginary
      information or assumptions regarding the behavior of others. 

PMID- 25849630
TI  - Spectroscopic Determination of Distinct Heme Ligands in Outer-Membrane Receptors
      PhuR and HasR of Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa PAO1 encodes two outer membrane receptors, PhuR
      (Pseudomonas heme uptake) and HasR (heme assimilation system). The HasR receptor
      acquires heme through interaction with a secreted hemophore, HasAp. The non
      hemophore-dependent PhuR is encoded along with proteins required for heme
      translocation into the cytoplasm. Herein, we report the isolation and
      characterization of the HasR and PhuR receptors. Absorption and MCD spectroscopy
      confirmed that, similar to other Gram-negative OM receptors, HasR coordinates
      heme through the conserved N-terminal plug His-221 and His-624 of the surface
      exposed FRAP-loop. In contrast, PhuR showed distinct absorption and MCD spectra
      consistent with coordination through a Tyr residue. Sequence alignment of PhuR
      with all known Gram-negative OM heme receptors revealed a lack of a conserved His
      within the FRAP loop but two Tyr residues at positions 519 and 529. Site-directed
      mutagenesis and spectroscopic characterization confirmed Tyr-519 and the N
      terminal plug His-124 provide the heme ligands in PhuR. We propose that PhuR and
      HasR represent nonredundant heme receptors capable of sensing and accessing heme
      across a wide range of physiological conditions on colonization and infection of
      the host. 

PMID- 25849632
TI  - Aspirin resistance in the acute stages of acute ischemic stroke is associated
      with the development of new ischemic lesions.
AB  - BACKGROUND: Aspirin is a primary antiplatelet agent for the secondary prevention
      of ischemic stroke. However, if aspirin fails to inhibit platelet function, as is
      expected in acute ischemic stroke (AIS), it may increase the rate of early
      clinical events. Therefore, we sought to determine whether aspirin resistance in
      the acute stage was associated with early radiological events, including new
      ischemic lesions (NILs). METHODS: This study was a single-center, prospective,
      observational study conducted between April 2012 and May 2013. Aspirin 300 mg was
      initially administered followed by maintenance doses of 100 mg daily. The acute
      aspirin reaction unit (aARU) was consistently measured after 3 hours of aspirin
      loading. An aARU value >=550 IU was defined as biological aspirin resistance
      (BAR). NILs on follow-up diffusion-weighted imaging (DWI) were defined as lesions
      separate from index lesions, which were not detected on the initial DWI. RESULTS:
      A total of 367 patients were analyzed in this study. BAR in aARU was detected in
      60 patients (16.3%). On follow-up DWI, 81 patients (22.1%) had NILs, which were
      frequently in the same territory as the index lesions (79%), pial infarcts
      (61.7%), and located within the cortex (59.3%). BAR was independently associated
      with NILs on follow-up DWI (adjusted OR 2.00, 95% CIs 1.01-3.96; p = 0.047).
      CONCLUSION: In conclusion, BAR in aARU could be associated with NILs on follow-up
      DWI in AIS. Therefore, a further prospective study with a longer follow-up period
      is necessary to evaluate the clinical implications of aARU in AIS.

PMID- 25849633
TI  - Expression and characterization of protein disulfide isomerase family proteins in
      bread wheat.
AB  - BACKGROUND: The major wheat seed proteins are storage proteins that are
      synthesized in the rough endoplasmic reticulum (ER) of starchy endosperm cells.
      Many of these proteins have intra- and intermolecular disulfide bonds. In
      eukaryotes, the formation of most intramolecular disulfide bonds in the ER is
      thought to be catalyzed by protein disulfide isomerase (PDI) family proteins. The
      cDNAs that encode eight groups of bread wheat (Triticum aestivum L.) PDI family
      proteins have been cloned, and their expression levels in developing wheat grains
      have been determined. The purpose of the present study was to characterize the
      enzymatic properties of the wheat PDI family proteins and clarify their
      expression patterns in wheat caryopses. RESULTS: PDI family cDNAs, which are
      categorized into group I (TaPDIL1Aalpha, TaPDIL1Abeta, TaPDIL1Agamma,
      TaPDIL1Adelta, and TaPDIL1B), group II (TaPDIL2), group III (TaPDIL3A), group IV
      (TaPDIL4D), and group V (TaPDIL5A), were cloned. The expression levels of
      recombinant TaPDIL1Aalpha, TaPDIL1B, TaPDIL2, TaPDIL3A, TaPDIL4D, and TaPDIL5A in
      Escherichia coli were established from the cloned cDNAs. All recombinant proteins
      were expressed in soluble forms and purified. Aside from TaPDIL3A, the
      recombinant proteins exhibited oxidative refolding activity on reduced and
      denatured ribonuclease A. Five groups of PDI family proteins were distributed
      throughout wheat caryopses, and expression levels of these proteins were higher
      during grain filling than in the late stage of maturing. Localization of these
      proteins in the ER was confirmed by fluorescent immunostaining of the immature
      caryopses. In mature grains, the five groups of PDI family proteins remained in
      the aleurone cells and the protein matrix of the starchy endosperm. CONCLUSIONS:
      High expression of PDI family proteins during grain filling in the starchy
      endosperm suggest that these proteins play an important role in forming
      intramolecular disulfide bonds in seed storage proteins. In addition, these PDI
      family proteins that remain in the aleurone layers of mature grains likely assist
      in folding newly synthesized hydrolytic enzymes during germination.

PMID- 25849634
TI  - Oep23 forms an ion channel in the chloroplast outer envelope.
AB  - BACKGROUND: Metabolite, ion and protein translocation into chloroplasts occurs
      across two membranes, the inner and the outer envelope. Solute and metabolite
      channels fulfill very important functions in integrating the organelles into the
      metabolic network of the cell. However so far only a few have been identified.
      Here we describe the identification and the characterization of the outer
      envelope protein of 23 kDa, Oep23 from garden pea. RESULTS: Oep23 is found in the
      entire plant lineage from green algae to flowering plants. It is expressed in all
      organs and developmental states tested so far. The reconstituted recombinant
      protein Oep23 from pea forms a high conductance ion channel with a maximal
      conductance in the fully open state of 466 +/- 14pS at a holding potential of
      +100 mV (in 250 mM KCl). The Oep23 channel is cation selective (PK+ : PCl- = 15 :
      1) with a voltage dependent open probability of maximal Vmem = 0 mV. CONCLUSION:
      The data indicate that the Oep23 activity represents a single channel unit and
      does not assemble into a multiple pore complex like bacterial type porins or
      mitochondrial voltage dependent anion channel. Thus, Oep23 represents a new
      member of ion channels in the outer envelope of chloroplasts involved in solute
      exchange.

PMID- 25849635
TI  - Quantifying cellular capacity identifies gene expression designs with reduced
      burden.
AB  - Heterologous gene expression can be a significant burden for cells. Here we
      describe an in vivo monitor that tracks changes in the capacity of Escherichia
      coli in real time and can be used to assay the burden imposed by synthetic
      constructs and their parts. We identify construct designs with reduced burden
      that predictably outperformed less efficient designs, despite having equivalent
      output. 

PMID- 25849636
TI  - Massively parallel delivery of large cargo into mammalian cells with light
      pulses.
AB  - We report a high-throughput platform for delivering large cargo elements into
      100,000 cells in 1 min. Our biophotonic laser-assisted surgery tool (BLAST)
      generates an array of microcavitation bubbles that explode in response to laser
      pulsing, forming pores in adjacent cell membranes through which cargo is gently
      driven by pressurized flow. The platform delivers large items including bacteria,
      enzymes, antibodies and nanoparticles into diverse cell types with high
      efficiency and cell viability. We used this platform to explore the intracellular
      lifestyle of Francisella novicida and discovered that the iglC gene is
      unexpectedly required for intracellular replication even after phagosome escape
      into the cell cytosol. 

PMID- 25849637
TI  - Correlation Map, a goodness-of-fit test for one-dimensional X-ray scattering
      spectra.
AB  - Assessing similarity between data sets with the reduced chi(2) test requires the
      estimation of experimental errors, which, if incorrect, may render statistical
      comparisons invalid. We report a goodness-of-fit test, Correlation Map (CorMap),
      for assessing differences between one-dimensional spectra independently of
      explicit error estimates, using only data point correlations. Using small-angle X
      ray scattering data, we demonstrate that CorMap maintains the power of the
      reduced chi(2) test; moreover, CorMap is also applicable to other physical
      experiments. 

PMID- 25849638
TI  - Sequencing small genomic targets with high efficiency and extreme accuracy.
AB  - The detection of minority variants in mixed samples requires methods for
      enrichment and accurate sequencing of small genomic intervals. We describe an
      efficient approach based on sequential rounds of hybridization with biotinylated
      oligonucleotides that enables more than 1-million-fold enrichment of genomic
      regions of interest. In conjunction with error-correcting double-stranded
      molecular tags, our approach enables the quantification of mutations in
      individual DNA molecules. 

PMID- 25849639
TI  - The F-box protein MAX2 contributes to resistance to bacterial phytopathogens in
      Arabidopsis thaliana.
AB  - BACKGROUND: The Arabidopsis thaliana F-box protein MORE AXILLARY GROWTH2 (MAX2)
      has previously been characterized for its role in plant development. MAX2 appears
      essential for the perception of the newly characterized phytohormone
      strigolactone, a negative regulator of polar auxin transport in Arabidopsis.
      RESULTS: A reverse genetic screen for F-box protein mutants altered in their
      stress responses identified MAX2 as a component of plant defense. Here we show
      that MAX2 contributes to plant resistance against pathogenic bacteria.
      Interestingly, max2 mutant plants showed increased susceptibility to the
      bacterial necrotroph Pectobacterium carotovorum as well as to the hemi-biotroph
      Pseudomonas syringae but not to the fungal necrotroph Botrytis cinerea. max2
      mutant phenotype was associated with constitutively increased stomatal
      conductance and decreased tolerance to apoplastic ROS but also with alterations
      in hormonal balance. CONCLUSIONS: Our results suggest that MAX2 previously
      characterized for its role in regulation of polar auxin transport in Arabidopsis,
      and thus plant development also significantly influences plant disease
      resistance. We conclude that the increased susceptibility to P. syringae and P.
      carotovorum is due to increased stomatal conductance in max2 mutants promoting
      pathogen entry into the plant apoplast. Additional factors contributing to
      pathogen susceptibility in max2 plants include decreased tolerance to pathogen
      triggered apoplastic ROS and alterations in hormonal signaling.

PMID- 25849640
TI  - Design and fabrication of magnetically functionalized flexible micropillar arrays
      for rapid and controllable microfluidic mixing.
AB  - Magnetically functionalized PDMS-based micropillar arrays have been successfully
      designed, fabricated and implanted for controllable microfluidic mixing. The
      arrangement of PDMS micropillar arrays inside the microchannel can be flexibly
      controlled by an external magnetic field. As a consequence, the flow fields
      inside the microchannel can be regulated at will via magnetic activation
      conveniently. When a microchannel is implanted with such micropillar arrays, two
      microstreams can be mixed easily and controllably upon the simple application of
      an on/off magnetic signal. Mixing efficiencies based on micropillar arrays with
      different densities were investigated and compared. It was found that micropillar
      arrays with higher density (i.e. smaller pillar pitch) would render better mixing
      performance. Our microfluidic system is capable of generating highly reproducible
      results within many cycles of mixing/non-mixing conversion. We believe that the
      simple mixing-triggering method together with rapid and controllable mixing
      control will be extraordinarily valuable for various biological or chemical
      applications in the future. 

PMID- 25849641
TI  - Research trends in evidence-based medicine: a joinpoint regression analysis of
      more than 50 years of publication data.
AB  - BACKGROUND: Evidence-based medicine (EBM) has developed as the dominant paradigm
      of assessment of evidence that is used in clinical practice. Since its
      development, EBM has been applied to integrate the best available research into
      diagnosis and treatment with the purpose of improving patient care. In the EBM
      era, a hierarchy of evidence has been proposed, including various types of
      research methods, such as meta-analysis (MA), systematic review (SRV), randomized
      controlled trial (RCT), case report (CR), practice guideline (PGL), and so on.
      Although there are numerous studies examining the impact and importance of
      specific cases of EBM in clinical practice, there is a lack of research
      quantitatively measuring publication trends in the growth and development of EBM.
      Therefore, a bibliometric analysis was constructed to determine the scientific
      productivity of EBM research over decades. METHODS: NCBI PubMed database was used
      to search, retrieve and classify publications according to research method and
      year of publication. Joinpoint regression analysis was undertaken to analyze
      trends in research productivity and the prevalence of individual research
      methods. FINDINGS: Analysis indicates that MA and SRV, which are classified as
      the highest ranking of evidence in the EBM, accounted for a relatively small but
      auspicious number of publications. For most research methods, the annual percent
      change (APC) indicates a consistent increase in publication frequency. MA, SRV
      and RCT show the highest rate of publication growth in the past twenty years.
      Only controlled clinical trials (CCT) shows a non-significant reduction in
      publications over the past ten years. CONCLUSIONS: Higher quality research
      methods, such as MA, SRV and RCT, are showing continuous publication growth,
      which suggests an acknowledgement of the value of these methods. This study
      provides the first quantitative assessment of research method publication trends
      in EBM.

PMID- 25849642
TI  - A novel, rapid method to quantify intraplatelet calcium dynamics by ratiometric
      flow cytometry.
AB  - Cytosolic free calcium ions represent important second-messengers in platelets.
      Therefore, quantitative measurement of intraplatelet calcium provides a popular
      and very sensitive tool to evaluate platelet activation and reactivity. Current
      protocols for determination of intracellular calcium concentrations in platelets
      have a number of limitations. Cuvette-based methods do not allow measurement of
      calcium flux in complex systems, such as whole blood, and therefore require
      isolation steps that potentially interfere with platelet activation. Flow
      cytometry has the potential to overcome this limitation, but to date the
      application of calibrated, quantitative readout of calcium kinetics has only been
      described for Indo-1. As excitation of Indo-1 requires a laser in the ultraviolet
      range, such measurements cannot be performed with a standard flow cytometer.
      Here, we describe a novel, rapid calibration method for ratiometric calcium
      measurement in platelets using both Ar(+)-laser excited fluorescence dyes Fluo-4
      and Fura Red. We provide appropriate equations that allow rapid quantification of
      intraplatelet calcium fluxes by measurement of only two standardisation buffers.
      We demonstrate that this method allows quantitative calcium measurement in
      platelet rich plasma as well as in whole blood. Further, we show that this method
      prevents artefacts due to platelet aggregate formation and is therefore an ideal
      tool to determine basal and agonist induced calcium kinetics.

PMID- 25849643
TI  - Assessment of rival males through the use of multiple sensory cues in the
      fruitfly Drosophila pseudoobscura.
AB  - Environments vary stochastically, and animals need to behave in ways that best
      fit the conditions in which they find themselves. The social environment is
      particularly variable, and responding appropriately to it can be vital for an
      animal's success. However, cues of social environment are not always reliable,
      and animals may need to balance accuracy against the risk of failing to respond
      if local conditions or interfering signals prevent them detecting a cue. Recent
      work has shown that many male Drosophila fruit flies respond to the presence of
      rival males, and that these responses increase their success in acquiring mates
      and fathering offspring. In Drosophila melanogaster males detect rivals using
      auditory, tactile and olfactory cues. However, males fail to respond to rivals if
      any two of these senses are not functioning: a single cue is not enough to
      produce a response. Here we examined cue use in the detection of rival males in a
      distantly related Drosophila species, D. pseudoobscura, where auditory,
      olfactory, tactile and visual cues were manipulated to assess the importance of
      each sensory cue singly and in combination. In contrast to D. melanogaster, male
      D. pseudoobscura require intact olfactory and tactile cues to respond to rivals.
      Visual cues were not important for detecting rival D. pseudoobscura, while
      results on auditory cues appeared puzzling. This difference in cue use in two
      species in the same genus suggests that cue use is evolutionarily labile, and may
      evolve in response to ecological or life history differences between species.

PMID- 25849647
TI  - A novel microfluidic approach for extremely fast and efficient photochemical
      transformations in fluoropolymer microcapillary films.
AB  - The unique optical properties of the fluoropolymer microcapillary film (MCF)
      material combined with the extremely fast photoinactivation of Herpes HSV-1
      virus, and photodegradation of indigo carmine, diclofenac and benzoylecgonine in
      the MCF array photoreactor, demonstrate a new, flexible and inexpensive platform
      for rapid photochemical transformations, high-throughput process analytics and
      photochemical synthesis. 

PMID- 25849646
TI  - Short-term dietary salt supplementation blunts telmisartan induced increases in
      plasma renin activity in hypertensive patients with type 2 diabetes mellitus.
AB  - Current guidelines recommend low dietary salt intake (LDS) in patients with
      diabetes to reduce blood pressure (BP). However, low salt intake has been
      associated with higher mortality rates in people with diabetes. Our aim is to
      examine the effect of angiotensin II receptor blocker (ARB), telmisartan, with
      and without dietary sodium chloride (NaCl) supplementation, on BP [mean arterial
      pressure (MAP)], plasma renin activity (PRA), serum aldosterone level and
      estimated glomerular filtration rate (eGFR) in hypertensive patients with type 2
      diabetes. In a randomized, double-blind, placebo-controlled study (RCT), 28
      patients with type 2 diabetes, treated with telmisartan (40 mg daily), received 2
      weeks of placebo or NaCl capsules (100 mmol/24 h). Following a 6-week washout,
      the protocol was repeated in reverse. Twenty-four-hour urinary sodium excretion
      (24hUNa), ambulatory BP (ABP) monitoring and blood tests were performed before
      and after each study phase. The telmisartan-associated increase in PRA was
      blunted by approximately 50% during salt supplementation compared with placebo;
      median PRA was 2.3 MUg/l/h with placebo compared with 1.7 MUg/l/h with salt
      (P<0.001). A trend towards blunting of ARB induced increases in serum aldosterone
      was also demonstrated. Salt supplementation significantly reduced the MAP
      lowering effects of telmisartan (P<0.05). The present study demonstrates that
      salt supplementation blunts the telmisartan induced increase in PRA in patients
      with type 2 diabetes. 

PMID- 25849644
TI  - Signaling through IL-17C/IL-17RE is dispensable for immunity to systemic, oral
      and cutaneous candidiasis.
AB  - Candida albicans is a commensal fungal microbe of the human orogastrointestinal
      tract and skin. C. albicans causes multiple forms of disease in immunocompromised
      patients, including oral, vaginal, dermal and disseminated candidiasis. The
      cytokine IL-17 (IL-17A) and its receptor subunits, IL-17RA and IL-17RC, are
      required for protection to most forms of candidiasis. The importance of the IL
      17R pathway has been observed not only in knockout mouse models, but also in
      humans with rare genetic mutations that impact generation of Th17 cells or the IL
      17 signaling pathway, including Hyper-IgE Syndrome (STAT3 or TYK2 mutations) or
      IL17RA or ACT1 gene deficiency. The IL-17 family of cytokines is a distinct
      subclass of cytokines with unique structural and signaling properties. IL-17A is
      the best-characterized member of the IL-17 family to date, but far less is known
      about other IL-17-related cytokines. In this study, we sought to determine the
      role of a related IL-17 cytokine, IL-17C, in protection against oral, dermal and
      disseminated forms of C. albicans infection. IL-17C signals through a
      heterodimeric receptor composed of the IL-17RA and IL-17RE subunits. We observed
      that IL-17C mRNA was induced following oral C. albicans infection. However, mice
      lacking IL-17C or IL-17RE cleared C. albicans infections in the oral mucosa, skin
      and bloodstream at rates similar to WT littermate controls. Moreover, these mice
      demonstrated similar gene transcription profiles and recovery kinetics as WT
      animals. These findings indicate that IL-17C and IL-17RE are dispensable for
      immunity to the forms of candidiasis evaluated, and illustrate a surprisingly
      limited specificity of the IL-17 family of cytokines with respect to systemic,
      oral and cutaneous Candida infections. 

PMID- 25849645
TI  - Decrease in plasma levels of alpha-synuclein is evident in patients with
      Parkinson's disease after elimination of heterophilic antibody interference.
AB  - There is substantial biochemical, pathological, and genetic evidence that alpha
      synuclein (A-syn) is a principal molecule in the pathogenesis of Parkinson
      disease (PD). We previously reported that total A-syn levels in cerebrospinal
      fluid (CSF), measured with the specific enzyme-linked immunosorbent assay (ELISA)
      developed by ourselves, were decreased in patients with PD, and suggested the
      usefulness of A-syn in CSF and plasma as a biomarker for the diagnosis of PD.
      After our report, a considerable number of studies have investigated the levels A
      syn in CSF and in blood, but have reported inconclusive results. Such
      discrepancies have often been attributed not only to the use of different
      antibodies in the ELISAs but also to interference from hemolysis. In this study
      we measured the levels of A-syn in CSF and plasma by using our own sandwich ELISA
      with or without heterophilic antibody (HA) inhibitor in 30 patients with PD and
      58 age-matched controls. We thereby revealed that HA interfered with ELISA
      measurements of A-syn and are accordingly considered to be an important
      confounder in A-syn ELISAs. HA produced falsely exaggerated signals in A-syn
      ELISAs more prominently in plasma samples than in CSF samples. After elimination
      of HA interference, it was found that hemolysis did not have a significant effect
      on the signals obtained using our A-syn ELISA. Furthermore, plasma levels of A
      syn were significantly lower in the PD group compared with the control group
      following elimination of HA interference with an HA inhibitor. Our results
      demonstrate that HA was a major confounder that should be controlled in A-syn
      ELISAs, and that plasma A-syn could be a useful biomarker for the diagnosis of PD
      if adequately quantified following elimination of HA interference. 

PMID- 25849648
TI  - Validity of a Trunk-Mounted Accelerometer to Measure Physical Collisions in
      Contact Sports.
AB  - CONTEXT: Accelerometer peak impact accelerations are being used to measure player
      physical demands in contact sports. However, their accuracy to do so has not been
      ascertained. PURPOSE: To compare peak-impact-acceleration data from an
      accelerometer contained in a wearable tracking device with a 3-dimensional motion
      analysis (MA) system during tackling and bumping. METHODS: Twenty-five semielite
      rugby athletes wore a tracking device containing a 100-Hz triaxial accelerometer
      (MinimaxX S4, Catapult Innovations, Australia). A single retroreflective marker
      was attached to the device, with its position recorded by a 12-camera MA system
      during 3 physical-collision tasks (tackle bag, bump pad, and tackle drill; N =
      625). The accuracy, effect size, agreement, precision, and relative errors for
      each comparison were obtained as measures of accelerometer validity. RESULTS:
      Physical-collision peak impact accelerations recorded by the accelerometer
      overestimated (mean bias 0.60 g) those recorded by the MA system (P < .01).
      Filtering the raw data at a 20-Hz cutoff improved the accelerometer's
      relationship with MA data (mean bias 0.01 g; P > .05). When considering the data
      in 9 magnitude bands, the strongest relationship with the MA system was found in
      the 3.0-g or less band, and the precision of the accelerometer tended to reduce
      as the magnitude of impact acceleration increased. Of the 3 movements performed,
      the tackle-bag task displayed the greatest validity with MA. CONCLUSIONS: The
      findings indicate that the MinimaxX S4 accelerometer can accurately measure
      physical-collision peak impact accelerations when data are filtered at a 20-Hz
      cutoff frequency. As a result, accelerometers may be useful to measure physical
      collisions in contact sports.

PMID- 25849649
TI  - Vitamin D status and the risk for hospital-acquired infections in critically ill
      adults: a prospective cohort study.
AB  - INTRODUCTION: To identify patient characteristics associated with low serum 25
      hydroxyvitamin D (25(OH)D) concentrations in the medical intensive care unit
      (ICU) and examine the relationship between serum 25(OH)D and the risk for
      hospital-acquired infections. METHODS: This is a prospective observational cohort
      of adult patients admitted to the medical ICU at an urban safety net teaching
      hospital in Atlanta, Georgia from November 1, 2011 through October 31, 2012 with
      an anticipated ICU stay >= 1 day. Phlebotomy for serum 25(OH)D measurement was
      performed on all patients within 5 days of ICU admission. Patients were followed
      for 30 days or until death or hospital discharge, whichever came first. Hospital
      acquired infections were determined using standardized criteria from review of
      electronic medical record. RESULTS: Among the 314 patients analyzed, 178 (57%)
      had a low vitamin D at a serum 25(OH)D concentration < 15 ng/mL. The patient
      characteristics associated with low vitamin D included admission during winter
      months (28% vs. 18%, P = 0.04), higher PaO2/FiO2 (275 vs. 226 torr, P = 0.03) and
      a longer time from ICU admission to study phlebotomy (1.8 vs. 1.5 days, P =
      0.02). A total of 36 (11%) patients were adjudicated as having a hospital
      acquired infection and in multivariable analysis adjusting for gender, alcohol
      use, APACHE II score, time to study phlebotomy, ICU length of stay and net fluid
      balance, serum 25(OH)D levels < 15 ng/mL were not associated with risk for
      hospital-acquired infections (HR 0.85, 95% CI 0.40-1.80, P = 0.7). CONCLUSIONS:
      In this prospective, observational cohort of adults admitted to a single-center
      medical ICU, we did not find a significant association between low 25(OH)D and
      the risk for hospital-acquired infections.

PMID- 25849650
TI  - Role of glucokinase in the subcellular localization of glucokinase regulatory
      protein.
AB  - Glucokinase (GCK) is the rate-limiting enzyme of liver glucose metabolism.
      Through protein-protein interactions, glucokinase regulatory protein (GCKR) post
      transcriptionally regulates GCK function in the liver, and causes its nuclear
      localization. However the role of GCK in regulating GCKR localization is unknown.
      In the present study, using in vitro and in vivo models, we examined the levels
      of GCK and GCKR, and their subcellular localization. We found that total cellular
      levels of GCKR did not vary in the in vivo models, but its subcellular
      localization did. In animals with normal levels of GCK, GCKR is mainly localized
      to the nuclei of hepatocytes. In seven-day old rats and liver-specific Gck gene
      knockout mice (animals that lack or have reduced levels of GCK protein), GCKR was
      found primarily in the cytoplasm. The interaction of GCK with GCKR was further
      examined using in vitro models where we varied the levels of GCK and GCKR.
      Varying the level of GCK protein had no effect on total cellular GCKR protein
      levels. Taken together, our results indicate that GCK is important for the
      localization of GCKR to the nucleus and raises the possibility that GCKR may have
      functions in addition to those regulating GCK activity in the cytoplasm. 

PMID- 25849651
TI  - Identification of inhibitors of biological interactions involving intrinsically
      disordered proteins.
AB  - Protein-protein interactions involving disordered partners have unique features
      and represent prominent targets in drug discovery processes. Intrinsically
      Disordered Proteins (IDPs) are involved in cellular regulation, signaling and
      control: they bind to multiple partners and these high-specificity/low-affinity
      interactions play crucial roles in many human diseases. Disordered regions,
      terminal tails and flexible linkers are particularly abundant in DNA-binding
      proteins and play crucial roles in the affinity and specificity of DNA
      recognizing processes. Protein complexes involving IDPs are short-lived and
      typically involve short amino acid stretches bearing few "hot spots", thus the
      identification of molecules able to modulate them can produce important lead
      compounds: in this scenario peptides and/or peptidomimetics, deriving from
      structure-based, combinatorial or protein dissection approaches, can play a key
      role as hit compounds. Here, we propose a panoramic review of the structural
      features of IDPs and how they regulate molecular recognition mechanisms focusing
      attention on recently reported drug-design strategies in the field of IDPs. 

PMID- 25849652
TI  - The relevance of miRNA-21 in HSV-induced inflammation in a mouse model.
AB  - The purpose of this study was to clarify the correlation between microRNA-21 (miR
      21) expression and inflammation in a herpes simplex virus (HSV)-induced Behcet's
      Disease (BD) mouse model. miR-21 was compared between BD patients and healthy
      controls in peripheral blood mononuclear cells (PBMC). For miR-21 inhibition, miR
      21 antagomir was applied to BD mice. The change of symptoms was monitored. The
      levels of cytokines and related molecules were determined by ELISA and real time
      qPCR. Treatment with colchicine or pentoxifylline down-regulated the level of miR
      21 with improved symptoms in mice. miR-21 inhibition was accompanied by down
      regulated serum levels of IL-17 and IL-6. The expression levels of PDCD4, RhoB,
      PD-1, IL-12p35, and toll-like receptor-4 were also regulated by miR-21
      inhibition. miR-21 was correlated with HSV-induced BD-like inflammation in mice
      and BD patients. The expression of miR-21 was regulated by antagomir in mice. 

PMID- 25849653
TI  - Thermoresponsive interplay of water insoluble poly(2-alkyl-2-oxazoline)s
      composition and supramolecular host-guest interactions.
AB  - A series of water insoluble poly[(2-ethyl-2-oxazoline)-ran-(2-nonyl-2-oxazoline)]
      amphiphilic copolymers was synthesized and their solubility properties in the
      presence of different supramolecular host molecules were investigated. The
      resulting polymer-cavitand assemblies exhibited a thermoresponsive behavior that
      could be modulated by variation of the copolymer composition and length.
      Interestingly, the large number of hydrophobic nonyl units across the polymer
      chain induced the formation of kinetically-trapped nanoparticles in solution.
      These nanoparticles further agglomerate into larger aggregates at a temperature
      that is dependent on the polymer composition and the cavitand type and
      concentration. The present research expands the understanding on the
      supramolecular interactions between water insoluble copolymers and supramolecular
      host molecules. 

PMID- 25849654
TI  - Analysis of bacterial and archaeal communities along a high-molecular-weight
      polyacrylamide transportation pipeline system in an oil field.
AB  - Viscosity loss of high-molecular-weight partially hydrolyzed polyacrylamide
      (HPAM) solution was observed in a water injection pipeline before being injected
      into subterranean oil wells. In order to investigate the possible involvement of
      microorganisms in HPAM viscosity loss, both bacterial and archaeal community
      compositions of four samples collected from different points of the
      transportation pipeline were analyzed using PCR-amplification of the 16S rRNA
      gene and clone library construction method together with the analysis of
      physicochemical properties of HPAM solution and environmental factors. Further,
      the relationship between environmental factors and HPAM properties with
      microorganisms were delineated by canonical correspondence analysis (CCA).
      Diverse bacterial and archaeal groups were detected in the four samples. The
      microbial community of initial solution S1 gathered from the make-up tank is
      similar to solution S2 gathered from the first filter, and that of solution S3
      obtained between the first and the second filter is similar to that of solution
      S4 obtained between the second filter and the injection well. Members of the
      genus Acinetobacter sp. were detected with high abundance in S3 and S4 in which
      HPAM viscosity was considerably reduced, suggesting that they likely played a
      considerable role in HPAM viscosity loss. This study presents information on
      microbial community diversity in the HPAM transportation pipeline and the
      possible involvement of microorganisms in HPAM viscosity loss and biodegradation.
      The results will help to understand the microbial community contribution made to
      viscosity change and are beneficial for providing information for microbial
      control in oil fields.

PMID- 25849655
TI  - The neuronal-specific SGK1.1 (SGK1_v2) kinase as a transcriptional modulator of
      BAG4, Brox, and PPP1CB genes expression.
AB  - The Serum- and Glucocorticoid-induced Kinase 1, SGK1, exhibits a broad range of
      cellular functions that include regulation of the number of ion channels in
      plasma membrane and modulation of signaling pathways of cell survival. This
      diversity of functions is made possible by various regulatory processes acting
      upon the SGK1 gene, giving rise to various isoforms: SGK1_v1-5, each with
      distinct properties and distinct aminotermini that serve to target proteins to
      different subcellular compartments. Among cellular effects of SGK1 expression is
      to indirectly modulate gene transcription by phosphorylating transcriptional
      factors of the FOXO family. Here we examined if SGK1.1 (SGK1_v2; NM_001143676),
      which associates primarily to the plasma membrane, is also able to regulate gene
      expression. Using a differential gene expression approach we identified six genes
      upregulated by SGK1.1 in HeLa cells. Further analysis of transcript and protein
      levels validated two genes: BCL2-associated athanogene 4 (BAG-4) and Brox. The
      results indicate that SGK1.1 regulates gene transcription upon a different set of
      genes some of which participate in cell survival pathways (BAG-4) and others in
      intracellular vesicular traffic (Brox). 

PMID- 25849656
TI  - SLM produced porous titanium implant improvements for enhanced vascularization
      and osteoblast seeding.
AB  - To improve well-known titanium implants, pores can be used for increasing bone
      formation and close bone-implant interface. Selective Laser Melting (SLM) enables
      the production of any geometry and was used for implant production with 250-um
      pore size. The used pore size supports vessel ingrowth, as bone formation is
      strongly dependent on fast vascularization. Additionally, proangiogenic factors
      promote implant vascularization. To functionalize the titanium with proangiogenic
      factors, polycaprolactone (PCL) coating can be used. The following proangiogenic
      factors were examined: vascular endothelial growth factor (VEGF), high mobility
      group box 1 (HMGB1) and chemokine (C-X-C motif) ligand 12 (CXCL12). As different
      surfaces lead to different cell reactions, titanium and PCL coating were
      compared. The growing into the porous titanium structure of primary osteoblasts
      was examined by cross sections. Primary osteoblasts seeded on the different
      surfaces were compared using Live Cell Imaging (LCI). Cross sections showed cells
      had proliferated, but not migrated after seven days. Although the cell count was
      lower on titanium PCL implants in LCI, the cell count and cell spreading area
      development showed promising results for titanium PCL implants. HMGB1 showed the
      highest migration capacity for stimulating the endothelial cell line. Future
      perspective would be the incorporation of HMGB1 into PCL polymer for the
      realization of a slow factor release. 

PMID- 25849658
TI  - A new series of kinked liquid crystals: 2-(6-alkoxynaphthalen-2-yl)-6
      methoxyquinolines.
AB  - A new series of 2-(6-alkoxynaphthalen-2-yl)-6-methoxyquinolines (nO-NpQOMe, n = 3
      8) liquid crystal compounds, a linear molecular structure with two kinks, were
      synthesized using a short two-step reaction with overall yields between 43% and
      58%. Spectral analyses were in accord with the expected structures. Thermotropic
      behavior of these liquid crystal compounds were investigated using polarized
      optical microscopy and differential scanning calorimetry. All compounds exhibited
      purely enantiotropic nematic phase at the medium-high temperature range of 162.4
      234.2  degrees C. However, short ranges of nematic phase, 20.5-16.6  degrees C at
      heating and 46.7-37.0  degrees C at cooling, were observed in these linear liquid
      crystalline compounds with two kinks. 

PMID- 25849657
TI  - Impacts of gut bacteria on human health and diseases.
AB  - Gut bacteria are an important component of the microbiota ecosystem in the human
      gut, which is colonized by 1014 microbes, ten times more than the human cells.
      Gut bacteria play an important role in human health, such as supplying essential
      nutrients, synthesizing vitamin K, aiding in the digestion of cellulose, and
      promoting angiogenesis and enteric nerve function. However, they can also be
      potentially harmful due to the change of their composition when the gut ecosystem
      undergoes abnormal changes in the light of the use of antibiotics, illness,
      stress, aging, bad dietary habits, and lifestyle. Dysbiosis of the gut bacteria
      communities can cause many chronic diseases, such as inflammatory bowel disease,
      obesity, cancer, and autism. This review summarizes and discusses the roles and
      potential mechanisms of gut bacteria in human health and diseases. 

PMID- 25849660
TI  - Treat the brain and treat the periphery: toward a holistic approach to major
      depressive disorder.
AB  - The limited medication for major depressive disorder (MDD) against an ever-rising
      disease burden presents an urgent need for therapeutic innovations. During recent
      years, studies looking at the systems regulation of mental health and disease
      have shown a remarkably powerful control of MDD by systemic signals. Meanwhile,
      the identification of a host of targets outside the brain opens the way to treat
      MDD by targeting systemic signals. We examine these emerging findings and
      consider the implications for current thinking regarding MDD pathogenesis and
      treatment. We highlight the opportunities and challenges of a periphery-targeting
      strategy and propose its incorporation into a holistic approach. 

PMID- 25849659
TI  - Chromatin function modifying elements in an industrial antibody production
      platform--comparison of UCOE, MAR, STAR and cHS4 elements.
AB  - The isolation of stably transfected cell lines suitable for the manufacture of
      biotherapeutic protein products can be an arduous process relying on the
      identification of a high expressing clone; this frequently involves transgene
      amplification and maintenance of the clones' expression over at least 60
      generations. Maintenance of expression, or cell line stability, is highly
      dependent upon the nature of the genomic environment at the site of transgene
      integration, where epigenetic mechanisms lead to variable expression and
      silencing in the vast majority of cases. We have assessed four chromatin function
      modifying elements (A2UCOE, MAR X_S29, STAR40 and cHS4) for their ability to
      negate chromatin insertion site position effects and their ability to express and
      maintain monoclonal antibody expression. Each element was analysed by insertion
      into different positions within a vector, either flanking or between heavy chain
      (HC) and light chain (LC) antibody expression cassettes. Our results clearly show
      that the A2UCOE is the most beneficial element in this system, with stable cell
      pools and clones increasing antibody yields 6.5-fold and 6.75-fold respectively.
      Stability analysis demonstrated that the reduction in antibody expression, seen
      with cells transfected with the control vector over 120 generations, was
      mitigated in the clones containing A2UCOE-augmented transgenes. Analysis also
      showed that the A2UCOE reduced the amount of transgene promoter DNA methylation,
      which contributed to the maintenance of starting levels of expression. 

PMID- 25849661
TI  - Palladium-catalyzed carbonylative Sonogashira coupling between aryl triazenes and
      alkynes.
AB  - We developed a palladium-catalyzed carbonylative Sonogashira reaction with aryl
      triazenes and alkynes as substrates and methanesulfonic acid as the additive. A
      series of alpha,beta-ynones were synthesized by this alternative procedure.
      Notably, bromides, iodides and hydroxyl groups could be well-tolerated under
      these reaction conditions. 

PMID- 25849662
TI  - Development and psychometric properties of an informant assessment scale of
      theory of mind for adults with traumatic brain injury.
AB  - Impairment of theory of mind (ToM) is a common phenomenon following traumatic
      brain injury (TBI) that has clear effects on patients' social functioning. A
      growing body of research has focused on this area, and several methods have been
      developed to assess ToM deficiency. Although an informant assessment scale would
      be useful for examining individuals with TBI, very few studies have adopted this
      approach. The purpose of the present study was to develop an informant assessment
      scale of ToM for adults with traumatic brain injury (IASToM-aTBI) and to test its
      reliability and validity with 196 adults with TBI and 80 normal adults. A 44-item
      scale was developed following a literature review, interviews with patient
      informants, consultations with experts, item analysis, and exploratory factor
      analysis (EFA). The following three common factors were extracted: social
      interaction, understanding of beliefs, and understanding of emotions. The
      psychometric analyses indicate that the scale has good internal consistency
      reliability, split-half reliability, test-retest reliability, inter-rater
      reliability, structural validity, discriminate validity and criterion validity.
      These results provide preliminary evidence that supports the reliability and
      validity of the IASToM-aTBI as a ToM assessment tool for adults with TBI. 

PMID- 25849663
TI  - Increase of microRNA-210, decrease of raptor gene expression and alteration of
      mammalian target of rapamycin regulated proteins following mithramycin treatment
      of human erythroid cells.
AB  - Expression and regulation of microRNAs is an emerging issue in erythroid
      differentiation and globin gene expression in hemoglobin disorders. In the first
      part of this study microarray analysis was performed both in mithramycin-induced
      K562 cells and erythroid precursors from healthy subjects or beta-thalassemia
      patients producing low or high levels of fetal hemoglobin. We demonstrated that:
      (a) microRNA-210 expression is higher in erythroid precursors from beta
      thalassemia patients with high production of fetal hemoglobin; (b) microRNA-210
      increases as a consequence of mithramycin treatment of K562 cells and human
      erythroid progenitors both from healthy and beta-thalassemia subjects; (c) this
      increase is associated with erythroid induction and elevated expression of gamma
      globin genes; (d) an anti-microRNA against microRNA-210 interferes with the
      mithramycin-induced changes of gene expression. In the second part of the study
      we have obtained convergent evidences suggesting raptor mRNA as a putative target
      of microRNA-210. Indeed, microRNA-210 binding sites of its 3'-UTR region were
      involved in expression and are targets of microRNA-210-mediated modulation in a
      luciferase reporter assays. Furthermore, (i) raptor mRNA and protein are down
      regulated upon mithramycin-induction both in K562 cells and erythroid progenitors
      from healthy and beta-thalassemia subjects. In addition, (ii) administration of
      anti-microRNA-210 to K562 cells decreased endogenous microRNA-210 and increased
      raptor mRNA and protein expression. Finally, (iii) treatment of K562 cells with
      premicroRNA-210 led to a decrease of raptor mRNA and protein. In conclusion,
      microRNA-210 and raptor are involved in mithramycin-mediated erythroid
      differentiation of K562 cells and participate to the fine-tuning and control of
      gamma-globin gene expression in erythroid precursor cells. 

PMID- 25849664
TI  - Serum metalloproteinase-9 is related to COPD severity and symptoms - cross
      sectional data from a population based cohort-study.
AB  - BACKGROUND: Chronic obstructive pulmonary disease, COPD, is an increasing cause
      of morbidity and mortality worldwide, and an imbalance between proteases and
      antiproteases has been implicated to play a role in COPD pathogenesis. Matrix
      metalloproteinases (MMP) are important proteases that along with their
      inhibitors, tissue inhibitors of metalloproteinases (TIMP), affect homeostasis of
      elastin and collagen, of importance for the structural integrity of human
      airways. Small observational studies indicate that these biomarkers are involved
      in the pathogenesis of COPD. The aim of this study was to investigate serum
      levels of MMP-9 and TIMP-1 in a large Swedish population-based cohort, and their
      association with disease severity and important clinical symptoms of COPD such as
      productive cough. METHODS: Spirometry was performed and peripheral blood samples
      were collected in a populations-based cohort (median age 67 years) comprising
      subjects with COPD (n = 594) and without COPD (n = 948), in total 1542
      individuals. Serum MMP-9 and TIMP-1 concentrations were measured with enzyme
      linked immunosorbant assay (ELISA) and related to lung function data and
      symptoms. RESULTS: Median serum MMP-9 values were significantly higher in COPD
      compared with non-COPD 535 vs. 505 ng/ml (P = 0.017), without any significant
      differences in serum TIMP-1-levels or MMP-9/TIMP-1-ratio. In univariate analysis,
      productive cough and decreasing FEV1% predicted correlated significantly with
      increased MMP-9 among subjects with COPD (P = 0.004 and P = 0.001 respectively),
      and FEV1% predicted remained significantly associated to MMP-9 in a multivariate
      model adjusting for age, sex, pack years and productive cough (P = 0.033).
      CONCLUSION: Productive cough and decreasing FEV1 were each associated with MMP-9
      in COPD, and decreasing FEV1 remained significantly associated with MMP-9 also
      after adjustment for common confounders in this population-based COPD cohort. The
      increased serum MMP-9 concentrations in COPD indicate an enhanced proteolytic
      activity that is related to disease severity, and further longitudinal studies
      are important for the understanding of MMP-9 in relation to the disease process
      and the pathogenesis of different COPD phenotypes.

PMID- 25849665
TI  - Simultaneous discovery, estimation and prediction analysis of complex traits
      using a bayesian mixture model.
AB  - Gene discovery, estimation of heritability captured by SNP arrays, inference on
      genetic architecture and prediction analyses of complex traits are usually
      performed using different statistical models and methods, leading to inefficiency
      and loss of power. Here we use a Bayesian mixture model that simultaneously
      allows variant discovery, estimation of genetic variance explained by all
      variants and prediction of unobserved phenotypes in new samples. We apply the
      method to simulated data of quantitative traits and Welcome Trust Case Control
      Consortium (WTCCC) data on disease and show that it provides accurate estimates
      of SNP-based heritability, produces unbiased estimators of risk in new samples,
      and that it can estimate genetic architecture by partitioning variation across
      hundreds to thousands of SNPs. We estimated that, depending on the trait, 2,633
      to 9,411 SNPs explain all of the SNP-based heritability in the WTCCC diseases.
      The majority of those SNPs (>96%) had small effects, confirming a substantial
      polygenic component to common diseases. The proportion of the SNP-based variance
      explained by large effects (each SNP explaining 1% of the variance) varied
      markedly between diseases, ranging from almost zero for bipolar disorder to 72%
      for type 1 diabetes. Prediction analyses demonstrate that for diseases with major
      loci, such as type 1 diabetes and rheumatoid arthritis, Bayesian methods
      outperform profile scoring or mixed model approaches. 

PMID- 25849666
TI  - Engagement of Fas on Macrophages Modulates Poly I:C induced cytokine production
      with specific enhancement of IP-10.
AB  - Viral double-stranded RNA (dsRNA) is recognised by pathogen recognition receptors
      such as Toll-Like Receptor 3 (TLR3) and retinoic acid inducible gene-I (RIG-I),
      and results in cytokine and interferon production. Fas, a well characterised
      death receptor, has recently been shown to play a role in the inflammatory
      response. In this study we investigated the role of Fas in the anti-viral immune
      response. Stimulation of Fas on macrophages did not induce significant cytokine
      production. However, activation of Fas modified the response of macrophages to
      the viral dsRNA analogue poly I:C. In particular, poly I:C-induced IP-10
      production was significantly enhanced. A similar augmentation of IP-10 by Fas was
      observed following stimulation with both poly A:U and Sendai virus. Fas
      activation suppressed poly I:C-induced phosphorylation of the MAP kinases p38 and
      JNK, while overexpression of the Fas adaptor protein, Fas-associated protein with
      death domain (FADD), activated AP-1 and inhibited poly I:C-induced IP-10
      production. Consistent with an inhibitory role for AP-1 in IP-10 production,
      mutation of the AP-1 binding site on the IP-10 promoter resulted in augmented
      poly I:C-induced IP-10. These results demonstrate that engagement of the Fas
      receptor plays a role in modifying the innate immune response to viral RNA. 

PMID- 25849667
TI  - Nephrotic syndrome complicated with deep venous thrombosis in the upper
      extremities.
AB  - Deep venous thrombosis (DVT) in the upper extremities is a rare but important
      clinical illness, which leads to severe complications such as pulmonary embolism.
      Unlike DVT in the lower extremities, which is mainly induced by a hypercoagulable
      state, DVT in the upper extremities is usually caused by mechanical obstruction
      or anatomical stenosis in the venous system. We herein report a case in which DVT
      developed in the left upper limb during treatment of nephrotic syndrome. This is
      the first case report of upper-extremity DVT in association with nephrotic
      syndrome in the literature. Our patient was a 56-year-old male with nephrotic
      syndrome due to idiopathic membranous nephropathy who was treated with 40 mg/day
      of prednisolone. During corticosteroid therapy, he developed a swelling of the
      left upper limb. Computed tomography revealed thrombi in the left internal
      jugular vein and the left subclavian vein without anatomical abnormalities in his
      venous system. Thus, he was diagnosed with DVT of the upper extremities. After
      the initiation of warfarin treatment and subsequent regression of nephrotic
      syndrome, the swelling disappeared and the thrombi significantly diminished. DVT
      should be considered when upper-extremity edema is observed in patients with
      nephrotic syndrome. 

PMID- 25849668
TI  - A Case of IgG2 Heavy Chain Deposition Disease in a Patient with Kappa Positive
      Plasma Cell Dyscrasia.
AB  - IgG2 heavy chain deposition disease (HCDD) is extremely rare. To date, only 4
      cases have been reported in medical literature. To our knowledge, we report the
      first case of IgG2 HCDD accompanied by kappa plasma cell dyscrasia. 

PMID- 25849669
TI  - Minimally Invasive Endourological Techniques may Provide a Novel Method for
      Relieving Urinary Obstruction due to Ureterosciatic Herniation.
AB  - Ureterosciatic herniation, the protrusion of the hernia sac through the sciatic
      foramen, is an extremely rare cause of ureteral obstruction. We describe a case
      revealed by severe left back pain in a 72-year-old female. She was referred to
      our hospital for urological assessment of left hydronephrosis observed by
      ultrasonography. Intravenous ureterography (IVU) showed findings compatible with
      a left sciatic ureter, a dilated ureter with a fixed kinking, which is known as
      the 'curlicue' sign. We decided to attempt recovery of the herniated ureter using
      a retrograde approach. Ureteral stent placement was performed to decompress the
      dilated upper urinary tract. The ureterosciatic hernia was relieved with the
      passage of a flexible guide wire and a double-pigtail stent. Three months after
      ureteral stenting, she refused continuing to have an indwelling stent and the
      stent was removed. Thereafter, IVU revealed recurrent ureterosciatic hernia;
      however, there was no hydroureter or hydronephrosis. The patient is currently
      being under observation for 6 years after stenting and continues to be without
      hydronephrosis or symptoms. Placement of an internal stent possibly provides the
      rigidity to the ureter, thereby reducing the hernia and urinary obstruction. In
      the previous reports, most symptomatic patients have been treated surgically,
      with conservative therapy reserved for asymptomatic patients. For the patient who
      is elderly or a poor surgical candidate, retrograde stenting may provide safe
      reduction and efficacious treatment. This endourological approach provides a
      minimally invasive means for the management of urinary obstruction caused by
      ureterosciatic herniation. 

PMID- 25849670
TI  - Posterior reversible encephalopathy syndrome after renal transplant: a simple
      solution for a complicated patient.
AB  - BACKGROUND: Posterior reversible leukoencephalopathy syndrome (PRES) is
      characterized by an acute neurologic dysfunction coupled with characteristic
      findings on brain imaging. PRES occurs in the setting of hypertensive
      emergencies, eclampsia and as a neurotoxic effect of immunosuppressive agents.
      While overwhelmingly reversible without residual deficits when promptly
      recognized, vague symptomatology may delay the diagnosis of PRES.
      RESULTS/SUMMARY: A 50-year-old man who had undergone a recent kidney transplant
      was admitted to our clinic due to multiple episodes of seizure. He had no prior
      history of seizures or alcoholism. His transplantation had been without
      complication; he was discharged and given prednisone, tacrolimus, mycophenolate,
      acyclovir, trimethoprim-sulfamethoxazole, atenolol and enalapril. On the day of
      presentation, he experienced a severe headache, blurred vision and tonic-clonic
      seizure-like activity. His neurologic examination was limited by sedation,
      although no focal deficits were evident. Laboratory studies were unremarkable. A
      lumbar puncture revealed normal opening pressure, negative Gram stain, benign CSF
      analysis and India ink preparation. An MRI of the brain revealed bilateral
      enhancing parietal-occipital lesions, seen prominently on FLAIR sequence.
      Tacrolimus and all other medications were continued. The patient remained
      afebrile and normotensive and was extubated on the second hospital day. The
      patient reported no neurologic symptoms and was discharged on the third hospital
      day after a full recovery. CONCLUSIONS: While the outcome of PRES is typically
      benign, a delay in diagnosis may lead to permanent neurologic deficits, and
      misdiagnosis can be lethal. The cornerstone of treatment is removal of the
      offending agent or treatment of the underlying etiology. A clinical picture of
      headache, visual abnormalities, altered mentation and seizures is sufficient to
      prompt an empiric discontinuation of agents known to cause PRES. Calcineurin
      inhibitors such as tacrolimus are known to cause PRES, and in our patient,
      discontinuation led to a complete clinical resolution.

PMID- 25849671
TI  - A case report on allergic rash caused by icodextrin.
AB  - Icodextrin may be used as an alternative to glucose as the osmotic agent in
      peritoneal dialysis with ultrafiltration failure. In general, icodextrin is known
      to be safe and well tolerated, but it can also cause hypersensitivity reactions
      such as skin rashes. Allergic rashes are generally defined as erythematous, itchy
      and maculopapular, visible over the trunk and the extremities. When a rash
      occurs, it generally develops early in therapy, is self-limited, and resolves
      without sequelae after the discontinuation of icodextrin. Although the safety and
      efficacy of icodextrin peritoneal dialysis solution is well documented,
      clinicians should be aware of the possibility of severe adverse cutaneous
      reactions to it. We report the case of a 23-year-old female who developed a skin
      rash following the use of icodextrin. 

PMID- 25849672
TI  - Bucillamine-induced membranous nephropathy with crescent formation in a patient
      with rheumatoid arthritis: case report and literature review.
AB  - Bucillamine is a disease-modifying antirheumatic drug that is structurally
      similar to D-penicillamine. The major renal side effect of bucillamine and D
      penicillamine is proteinuria caused by membranous nephropathy (MN). In addition
      to MN, combined crescent formation has been occasionally reported in D
      penicillamine-induced MN, while crescent formation has been rarely reported in
      bucillamine-treated cases. Here, we describe a 76-year-old female who presented
      with nephrotic syndrome and rapidly progressive glomerulonephritis. She was
      receiving bucillamine as initial treatment for recently diagnosed rheumatoid
      arthritis, and renal biopsy showed MN with crescent formation. To the best of our
      knowledge, this is the first report of bucillamine-induced MN with crescent
      formation in the English literature. 

PMID- 25849673
TI  - A case of laparoscopic ureteric reimplantation in a solitary urinary system.
AB  - Ureteric strictures can be caused by traumatic pelvic surgery, urolithiasis and
      instrumentation. There are various treatment options for ureteric stricture,
      including laparoscopic ureteric reimplantation. A 56-year-old female with a
      history of chronic left pelviureteric junction obstruction presented with
      urosepsis secondary to right-sided urolithiasis. The patient had a left
      nephrectomy and developed right-sided ureteric stricture following repeated
      ureteroscopy to manage her stone disease. The treatment with ureteric stenting
      was unsuccessful. Here we present a case on the feasibility of laparoscopic
      reimplantation for ureteric stricture in a solitary kidney to preserve renal
      function and avoid further ureteroscopy or nephrostomies. 

PMID- 25849674
TI  - Acute Interstitial Nephritis and Membranous Nephropathy in the Context of IgG4
      Related Disease.
AB  - We present the case of a patient with IgG4-related disease, which manifested in
      an asynchronous manner as vitiligo, cholecystitis, sialadenitis, lymphadenopathy,
      facial palsy and kidney dysfunction. The patient underwent a renal biopsy, and a
      presumptive diagnosis of lupus nephritis was made due to compatible clinical and
      immunological findings. The biopsy revealed IgG4-related kidney disease with
      severe interstitial nephritis and membranous nephropathy. Corticosteroids
      treatment restored all disease manifestations. We bring this case to the
      attention of the nephrologists because of the protean, asynchronous,
      multisystemic nature of the disease that necessitates a multidisciplinary
      approach, a low threshold for kidney biopsy and a high index of suspicion for
      making the correct diagnosis and treatment. 

PMID- 25849675
TI  - A rare case of low-solute hyponatremia in a nonalcoholic person.
AB  - Low-solute hyponatremia is a relatively uncommon entity of euvolemic
      hyponatremia. Classic cases were described in alcoholics as beer potomania, which
      is characterized by hyponatremia in the setting of low-solute intake due to heavy
      beer drinking. We report a case of low-solute hyponatremia in a nonalcoholic
      person who was given a solute load, and, subsequently, had excessive diuresis
      with the resultant rapid increase in serum sodium concentration. 

PMID- 25849676
TI  - From cardio pulmonary bypass to ECMO, mechanical assist devices, quality control
      and decrease in 30 day mortality in cardiac anaesthesia - are we nearer our goal?

PMID- 25849677
TI  - Quality in cardiac anesthesia: is there an alternative to its practice?

PMID- 25849678
TI  - Extracorporeal circulation-from cardiopulmonary bypass to extracorporeal membrane
      oxygenation and mechanical cardiac assist device therapy: a constant evolution.

PMID- 25849680
TI  - 30-day mortality versus 1 year mortality in post cardiac surgery in adults.

PMID- 25849679
TI  - 30-day mortality after coronary artery bypass grafting and valve surgery has
      greatly improved over the last decade, but the 1-year mortality remains constant.
AB  - INTRODUCTION: European system for cardiac operative risk evaluation (EuroSCORE)
      is a valuable tool in control of the quality of cardiac surgery. However, the
      validity of the risk score for the individual patient may be questioned. The
      present study was carried out to investigate whether the continued fall in short
      term mortality reflects an actual improvement in late mortality, and
      subsequently, to investigate EuroSCORE as predictor of 1-year mortality. METHODS:
      A population-based cohort study of 25,602 patients from a 12-year period from
      three public university hospitals undergoing coronary artery bypass grafting
      (CABG) or valve surgery. Analysis was carried out based on EuroSCORE, age and co
      morbidity factors (residual EuroSCORE). RESULTS: During the period the average
      age increased from 65.1 +/- 10.0 years to 68.9 +/- 10.7 years (P < 0.001, one-way
      ANOVA), and the number of females increased from 26.0% to 28.2% (P = 0.0012, Chi
      square test). The total EuroSCORE increased from 4.67 to 5.68 while the residual
      EuroSCORE decreased from 2.64 to 1.83. Thirty-day mortality decreased from 4.07%
      in 1999-2000 to 2.44% in 2011-2012 (P = 0.0056; Chi-square test), while 1-year
      mortality was unchanged (6.50% in 1999-2000 vs. 6.25% in 2011-2012 [P = 0.8086;
      Chi-square test]). DISCUSSION: The study demonstrates that both co-morbidity and
      age has a great impact on 30-day mortality. However, with time the impact of co
      morbidity seems less. Thus, age is more important than co-morbidity in late
      mortality. The various developments in short and long-term mortality are not
      readily explained. CONCLUSION: Although 30-day mortality of CABG and valve
      surgery patients has decreased during the 12-year period, the 1-year mortality
      remains the same.

PMID- 25849681
TI  - Comparative effects of propofol and nitroglycerine on efficacy of rewarming in
      patients undergoing on-pump coronary artery bypass grafting.
AB  - OBJECTIVES: To compare the effects of propofol and nitroglycerine (NTG) on the
      efficacy of rewarming, extra volume added during cardiopulmonary bypass and
      extravascular lung water (EVLW) in patients undergoing on-pump coronary artery
      bypass grafting. MATERIALS AND METHODS: A prospective, randomized, blinded trial,
      twenty adult patients were randomly assigned to receive either NTG infusion (NTG
      group) or propofol infusion (propofol group) during rewarming. RESULTS: After
      drop in temperature at the end of surgery and till 24 h were significantly less
      in propofol group compare to NTG group (P < 0.025). Extra volume added during
      cardiopulmonary bypass and net crystalloid balance till 24 h was less in the
      propofol group (P < 0.003). There was no difference in EVLW and postoperative
      outcome. CONCLUSIONS: Propofol use during moderate hypothermic cardiopulmonary
      bypass is associated with less after drop in temperature and less requirement of
      extra fluid during the perioperative period.

PMID- 25849682
TI  - Pulmonary hypertension and pregnancy: the experience of a tertiary institution
      over 15 years.
AB  - BACKGROUND: Pulmonary hypertension (PH) in pregnancy is associated with a high
      maternal mortality and morbidity and has been found to be as high as 30-56%. AIM:
      To review the management of such patients in a tertiary center over a 15 year
      period, as the current literature consists of a few case reports, a few small
      case series and 2 meta-analyses. MATERIALS AND METHODS: A review of all patients
      admitted to our institution for management of PH in pregnancy between 1994 and
      February 2009 was undertaken. Cases were identified from the high-risk pregnancy
      database within the department of anesthesia and from the hospital medical
      records. Severity of PH, type of PH, NYHA functional status at presentation and
      delivery, mode of delivery, peripartum monitoring and APGAR scores were noted.
      Patients were reviewed by a multidisciplinary team and management planned
      accordingly. RESULTS: 19 eligible patients were identified. Patients who were
      significantly sick due to their PH were aggressively managed during pregnancy.
      Overall there was an improvement in NYHA functional status at the time of
      delivery. Epidural analgesia and anesthesia for labor and operatively delivery
      seem to be the ideal choice. CONCLUSION: Multidisciplinary approach is a key to
      the successful management of these patients. Secondary PH results in higher
      morbidity and mortality, in particular, older the age higher the maternal
      morbidity and mortality.

PMID- 25849684
TI  - Risk assessment scores in cardiac surgery.

PMID- 25849683
TI  - Does Parsonnet scoring model predict mortality following adult cardiac surgery in
      India?
AB  - AIMS AND OBJECTIVES: To validate the Parsonnet scoring model to predict mortality
      following adult cardiac surgery in Indian scenario. MATERIALS AND METHODS: A
      total of 889 consecutive patients undergoing adult cardiac surgery between
      January 2010 and April 2011 were included in the study. The Parsonnet score was
      determined for each patient and its predictive ability for in-hospital mortality
      was evaluated. The validation of Parsonnet score was performed for the total data
      and separately for the sub-groups coronary artery bypass grafting (CABG), valve
      surgery and combined procedures (CABG with valve surgery). The model calibration
      was performed using Hosmer-Lemeshow goodness of fit test and receiver operating
      characteristics (ROC) analysis for discrimination. Independent predictors of
      mortality were assessed from the variables used in the Parsonnet score by
      multivariate regression analysis. RESULTS: The overall mortality was 6.3% (56
      patients), 7.1% (34 patients) for CABG, 4.3% (16 patients) for valve surgery and
      16.2% (6 patients) for combined procedures. The Hosmer-Lemeshow statistic was
      <0.05 for the total data and also within the sub-groups suggesting that the
      predicted outcome using Parsonnet score did not match the observed outcome. The
      area under the ROC curve for the total data was 0.699 (95% confidence interval
      0.62-0.77) and when tested separately, it was 0.73 (0.64-0.81) for CABG, 0.79
      (0.63-0.92) for valve surgery (good discriminatory ability) and only 0.55 (0.26
      0.83) for combined procedures. The independent predictors of mortality determined
      for the total data were low ejection fraction (odds ratio [OR] - 1.7),
      preoperative intra-aortic balloon pump (OR - 10.7), combined procedures (OR -
      5.1), dialysis dependency (OR - 23.4), and re-operation (OR - 9.4). CONCLUSIONS:
      The Parsonnet score yielded a good predictive value for valve surgeries, moderate
      predictive value for the total data and for CABG and poor predictive value for
      combined procedures.

PMID- 25849685
TI  - Effect of etomidate and propofol induction on hemodynamic and endocrine response
      in patients undergoing coronary artery bypass grafting/mitral valve and aortic
      valve replacement surgery on cardiopulmonary bypass.
AB  - INTRODUCTION: The concerns for induction of anaesthesia in patients undergoing
      cardiac surgery include hemodynamic stability, attenuation of stress response and
      maintenance of balance between myocardial oxygen demand and supply. Various
      Intravenous anaesthetic agents like Thiopentone, Etomidate, Propofol, Midazolam,
      and Ketamine have been used for anesthetizing patients for cardiac surgeries.
      However, many authors have expressed concerns regarding induction with
      thiopentone, midazolam and ketamine. Hence, Propofol and Etomidate are preferred
      for induction in these patients. However, these two drugs have different
      characteristics. Etomidate is preferred for patients with poor left ventricular
      (LV) function as it provides stable cardiovascular profile. But there are
      concerns about reduction in adrenal suppression and serum cortisol levels.
      Propofol, on the other hand may cause a reduction in systemic vascular resistance
      and subsequent hypotension. Thus, this study was conducted to compare induction
      with these two agents in cardiac surgeries. METHODS: Baseline categorical and
      continuous variables were compared using Fisher's exact test and student's t test
      respectively. Hemodynamic variables were compared using student's t test for
      independent samples. The primary outcome (serum cortisol and blood sugar) of the
      study was compared using Wilcoxon Rank Sum test. The P value less than 0.05 was
      considered significant. RESULTS: Etomidate provides more stable hemodynamic
      parameters as compared to Propofol. Propofol causes vasodilation and may result
      in drop of systematic BP. Etomidate can therefore be safely used for induction in
      patients with good LV function for CABG/MVR/AVR on CPB without serious cortisol
      suppression lasting more than twenty-four hours.

PMID- 25849686
TI  - Induced apnea enhances image quality and visualization of cardiopulmonary
      anatomic during contrastenhanced cardiac computerized tomographic angiography in
      children.
AB  - OBJECTIVE: The purpose of our study was to determine the effect of induced apnea
      on quality of cardiopulmonary structures during computerized tomographic (CT)
      angiography images in children with congenital heart diseases. METHODS: Pediatric
      patients with congenital heart defects undergoing cardiac CT angiography at our
      facility in the past 3 years participated in this study. The earlier patients
      underwent cardiac CT angiography without induced apnea and while, later, apnea
      was induced in patients, which was followed by electrocardiogram gated cardiac CT
      angiography. General anesthesia was induced using sleep dose of intravenous
      propofol. After the initial check CT, on request by the radiologist, apnea was
      induced by the anesthesiologist by administering 1 mg/kg of intravenous
      suxamethonium. Soon after apnea ensued, the contrast was injected, and CT
      angiogram carried out. CT images in the "apnea group" were compared with those in
      "nonapnea group." After the completion of the procedure, the patients were mask
      ventilated with 100% oxygen till the spontaneous ventilation was restored.
      RESULTS: We studied 46 patients, of whom 36 with apnea and yet another 10
      without. The quality of the image, visualization of structures such as cardiac
      wall, outflow tracts, lung field, aortopulmonary shunts, and coronary arteries
      were analyzed and subjected to statistical analysis (Mann-Whitney U, Fischer's
      exact test and Pearson's Chi-square test). In the induced apnea group, overall
      image quality was considered excellent in 89% (n = 33) of the studies, while in
      the "no apnea group," only 30% of studies were excellent. Absent or minimal
      motion artifacts were seen in a majority of the studies in apnea group (94%). In
      the nonapnea group, the respiratory and body motion artifacts were severe in 50%,
      moderate in 30%, and minimal in 20%, but they were significantly lesser in the
      apnea group. All the studied parameters were statistically significant in the
      apnea group in contrast to nonapnea group (P < 0.000). CONCLUSION: The image
      quality of cardiac CT angiography greatly improves, and motion artifact
      significantly decreases with the use of induced apnea in pediatrics patients
      being evaluated for congenital heart disease. This technique poses no additional
      morbidity of significance.

PMID- 25849687
TI  - Simulation training for extracorporeal membrane oxygenation.
AB  - BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a complex treatment.
      Despite this, there are a lack of training programs designed to develop relevant
      clinical and nonclinical skills required for ECMO specialists. The aim of the
      current study was to describe the design, implementation and evaluation of a 1
      day simulation course for delivering training in ECMO. METHODS: A 1-day
      simulation course was developed with educational and intensive care experts.
      First, the delegates received a lecture on the principles of simulation training
      and the importance of human factors. This was, followed by a practical
      demonstration and discussion of the ECMO circuit, console components, circuit
      interactions effects and potential complications. There were then five ECMO
      simulation scenarios with debriefing that covered technical and nontechnical
      issues. The course culminated in a knowledge-based assessment. Course outcomes
      were assessed using purpose-designed questionnaires. RESULTS: We held 3 courses
      with a total of 14 delegates (9 intensive care nurses, 3 adult intensive care
      consultants and 2 ECMO technicians). Following the course, 8 (57%) gained
      familiarity in troubleshooting an ECMO circuit, 6 (43%) increased their
      familiarity with the ECMO pump and circuit, 8 (57%) perceived an improvement in
      their communication skills and 7 (50%) perceived an improvement in their
      leadership skills. At the end of the course, 13 (93%) delegates agreed that they
      felt more confident in dealing with ECMO. CONCLUSIONS: Simulation-training
      courses may increase knowledge and confidence in dealing with ECMO emergencies.
      Further studies are indicated to determine whether simulation training improves
      clinical outcomes and translates to reduced complication rates in patients
      receiving ECMO.

PMID- 25849688
TI  - Transesophageal echocardiography in NeoChord procedure.
AB  - BACKGROUND: Transapical off-pump mitral valve intervention with neochord
      implantation for degenerative mitral valve disease have been recently introduced
      in the surgical practice. The procedure is performed under 2D-3D transesophageal
      echocardiography guidance. METHODS: The use of 3D real-time transesophageal
      echocardiography provides more accurate information than 2D echocardiography only
      in all the steps of the procedure. In particular 3D echocardiography is mandatory
      for preoperative assessment of the morphology of the valve, for correct
      positioning of the neochord on the diseased segment , for the final tensioning of
      the chordae and for the final evaluation of the surgical result. RESULT AND
      CONCLUSION: This article is to outline the technical aspects of the
      transesophageal echocardiography guidance of the NeoChord procedure showing that
      the procedure can be performed only with a close and continuous interaction
      between the anesthesiologist and the cardiac surgeon.

PMID- 25849689
TI  - Intraoperative transesophageal echocardiographic assessment of left ventricular
      Tei index in congenital heart disease.
AB  - BACKGROUND: Use of the Tei index has not been described to assess myocardial
      function before or after surgery in pediatric patients. This study was designed
      to evaluate the left ventricular (LV) function using the Tei index pre- and post
      cardiopulmonary bypass in patients with lesion that result in a volume loaded
      right ventricle (RV). METHODS: Retrospective data on 55 patients who underwent
      repair of a cardiac defect were analyzed. Patients with volume overload RV (n =
      15) were compared to patients without volume overload but with other cardiac
      defects (n = 40). We reviewed pre- and post-operative LV myocardial performance
      index (Tei index). Tei index was obtained from transesophageal Doppler
      echocardiogram. RESULTS: Patients with right heart volume overload, the mean
      preoperative Tei index was 0.6, with a postoperative mean decrease of 0.207 (P =
      0.014). Patients without right heart volume overload, the mean preoperative Tei
      was 0.48 with no significant postoperative change (P = 0.82). CONCLUSION: Pre-
      and post-operative transesophageal echocardiogram assessment provides an easy and
      quick way of evaluating LV function intra-operatively using LV Tei index.
      Preoperative LV Tei index was greater in the RV volume overload defects
      indicating diminished LV global function. This normalized in the immediate
      postoperative period, implying an immediate improvement in LV function. In
      patients without right heart volume load, consist of other cardiac defects,
      demonstrated no changes in the pre- and post-operative LV Tei. This implies that
      LV function was similar after the surgery.

PMID- 25849691
TI  - Elevated postoperative serum procalcitonin is not indicative of bacterial
      infection in cardiac surgical patients.
AB  - BACKGROUND: Identifying infections early, commencing appropriate empiric
      antibiotic not only helps gain control early, but also reduces mortality and
      morbidity. Conventional cultures take about 5 days to identify infections. To
      identify the infections early biomarker like serum procalcitonin (SPC). AIMS: We
      studied the correlation of an elevated level of SPC and positive culture in
      elective adult patients undergoing cardiac surgery. METHODS: This prospective
      study was conducted from January to December 2013. SPC was checked in patients
      showing evidence of sepsis. Simultaneously, relevant culture was also undertaken.
      Correlation, specificity, and sensitivity of elevated SPC were checked. RESULTS:
      A total of 819 adult patients were included in the study. 43 of them had signs of
      infection and SPC levels were checked. Based on the level of SPC criteria, 10
      patients were diagnosed as "nil", out of them, 4 had culture-positive infections,
      17 were suggested to have "mild infection," 3 out those had culture positivity.
      None among the eleven patients suggested to have "moderate infection," had a
      positive culture, and one among the five suggested to have a severe infection had
      a positive culture. The sensitivity was 50% and the specificity 17%. The positive
      predictive value was 12% and the negative predictive value 60%. CONCLUSIONS: We
      failed to elicit positive correlation between elevated SPC levels and
      postoperative infection in cardio surgical patients.

PMID- 25849692
TI  - Video commentary on "ECMO for heart failure and post heart transplant".

PMID- 25849690
TI  - Ketamine in adult cardiac surgery and the cardiac surgery Intensive Care Unit: an
      evidence-based clinical review.
AB  - Ketamine is a unique anesthetic drug that provides analgesia, hypnosis, and
      amnesia with minimal respiratory and cardiovascular depression. Because of its
      sympathomimetic properties it would seem to be an excellent choice for patients
      with depressed ventricular function in cardiac surgery. However, its use has not
      gained widespread acceptance in adult cardiac surgery patients, perhaps due to
      its perceived negative psychotropic effects. Despite this limitation, it is
      receiving renewed interest in the United States as a sedative and analgesic drug
      for critically ill-patients. In this manuscript, the authors provide an evidence
      based clinical review of ketamine use in cardiac surgery patients for intensive
      care physicians, cardio-thoracic anesthesiologists, and cardio-thoracic surgeons.
      All MEDLINE indexed clinical trials performed during the last 20 years in adult
      cardiac surgery patients were included in the review. 

PMID- 25849693
TI  - Video commentary on "imaging the coronary sinus".

PMID- 25849694
TI  - Single lumen tube as endobronchial stent to manage left bronchial compression
      post total anomalous pulmonary venous connection repair.

PMID- 25849695
TI  - Is it really ruptured sinus of valsalva? The crucial role of comprehensive
      transesophageal echocardiography in clinical decision-making.

PMID- 25849696
TI  - Rational interpretation of transesophageal echocardiography hemodynamics in the
      Intensive Care Unit, post aortic valve replacement.

PMID- 25849698
TI  - A novel technique of anesthesia induction in supine position with impaled knife
      in the back.
AB  - Current technique of airway management for impaled knife in the back includes
      putting the patient in lateral position and intubation. We present here a novel
      technique of anesthesia induction (intubation and central line insertion) in a
      patient with impaled knife in the back which is simple and easily reproducible.
      This technique can be used for single lung ventilation using double lumen tube or
      bronchial blocker also if desired. 

PMID- 25849697
TI  - Echocardiographic detection of intimo-intimal intussusception in a patient with
      acute Stanford type A aortic dissection.
AB  - Intimo-intimal intussusception is a very rare and unusual complication of type A
      dissections, typically noted on TEE exam. It has been reported in a few cases in
      the cardiothoracic surgical and radiology literature, and even more rarely in the
      cardiac anesthesia/TEE literature. This uncommon variation occurs in severe,
      acute, type A dissections when the ascending aortic intima circumferentially
      strips and detaches from the media and forms a tube-like structure which may
      either prolapse antegrade into the ascending aortic lumen or retrograde into the
      left ventricular (LV) outflow tract and LV cavity. Antegrade intussusceptions may
      be severe enough to partially or completely occlude the ostia of the innominate,
      left common carotid, and left subclavian arteries producing acute neurologic
      symptoms. Retrograde intussusceptions may severely impair LV filling in diastole,
      can worsen aortic insufficiency, mitral regurgitation, as well as produce
      occlusion of the coronary ostia and acute coronary ischemia. Here, we describe
      the incidental finding of a retrograde intussusception that was not visualized on
      computed tomography scan but by intraoperative TEE examination, in a patient with
      a severe, extensive type A dissection.

PMID- 25849699
TI  - Role of perioperative transesophageal echocardiography in the management of
      adolescent truncus arteriosus: rare case report.
AB  - Truncus arteriosus (TA) is a rare congenital heart disease defined as a single
      arterial vessel arising from the heart that gives origin to the systemic,
      pulmonary and coronary circulations. The truncal valve in majority of the cases
      is tricuspid though quadricuspid and bicuspid valves have been reported. Patients
      with TA typically have a large nonrestrictive sub truncal ventricular septal
      defect. Survival of these infants beyond 1-year is uncommon. Here, we report a
      unique case of 12-year-old female patient with persistent TA who underwent
      surgical repair by using transesophageal echocardiography as a monitoring device
      during the perioperative management. 

PMID- 25849700
TI  - Feasibility and safety of on table extubation after corrective surgical repair of
      tetralogy of Fallot in a developing country: a case series.
AB  - Fast-track extubation is an established safe practice in pediatric congenital
      heart disease (CHD) surgical patients. On table extubation (OTE) in acyanotic CHD
      surgical patients is well established with validated safety profile. This
      practice is not yet reported in tetralogy of Fallot (TOF) cardiac surgical repair
      patients in developing countries. Evidence suggests that TOF total correction
      patients should be extubated early, as positive pressure ventilation has a
      negative impact on right ventricular function and the overall increase in post
      TOF repair complications such as low cardiac output state and arrhythmias. The
      objective of the case series was to determine the safety and feasibility of OTE
      in elective TOF total correction cardiac surgical patients with an integrated
      team approach. To the best of our knowledge, this is the first reported case
      series. A total of 8 elective male and female TOF patients were included.
      Standard anesthetic, surgical and perfusion techniques were used in these
      procedures. All patients were extubated in the operating room safely without any
      complications with the exception of one patient who continued to bleed for 3 h of
      postextubation at 2-3 ml/kg/h which was managed with transfusion of fresh frozen
      plasma at 15 mL/kg, packed red blood cells 10 mL/kg and bolus of transamine at 20
      mg/kg. Apart from better surgical and bypass techniques, the most important
      factor leading to successful OTE was an excellent analgesia. On the basis of the
      case series, it is suggested to extubate selected TOF cardiac surgery repair
      patients on table safely with integrated multidisciplinary approach. 

PMID- 25849701
TI  - Perioperative intra-aortic balloon counterpulsation in a patient with myocardium
      at risk undergoing urgent noncardiac surgery.
AB  - We are presenting the case of a 76-year-old female scheduled for major abdominal
      surgery. Her past medical history was remarkable for a three-vessel coronary
      artery disease, with a severely impaired left ventricular function. She had
      already undergone complex coronary artery bypass surgery. Currently, she
      presented with the rare constellation of a hemodynamic relevant and
      interventionally intractable stenosis of the left subclavian artery proximal to a
      crucial coronary bypass from left internal mammary artery to the left anterior
      descending. To protect this patient from perioperative myocardial infarction, an
      intra-aortic balloon pump was successfully used. 

PMID- 25849702
TI  - Transcatheter, valve-in-valve transapical aortic and mitral valve implantation,
      in a high risk patient with aortic and mitral prosthetic valve stenoses.
AB  - Transcatheter valve implantation continues to grow worldwide and has been used
      principally for the nonsurgical management of native aortic valvular disease-as a
      potentially less invasive method of valve replacement in high-risk and inoperable
      patients with severe aortic valve stenosis. Given the burden of valvular heart
      disease in the general population and the increasing numbers of patients who have
      had previous valve operations, we are now seeing a growing number of high-risk
      patients presenting with prosthetic valve stenosis, who are not potential
      surgical candidates. For this high-risk subset transcatheter valve delivery may
      be the only option. Here, we present an inoperable patient with severe,
      prosthetic valve aortic and mitral stenosis who was successfully treated with a
      trans catheter based approach, with a valve-in-valve implantation procedure of
      both aortic and mitral valves. 

PMID- 25849703
TI  - Laparoscopic colectomy in an adult with single ventricle physiology: anesthetic
      implications and management.
AB  - Increasing numbers of adult patients with complex congenital heart conditions are
      presenting for noncardiac surgery later in life. These disorders can present
      challenges for surgical and anesthesia providers. Specifically, single ventricle
      lesions offer anatomic and physiologic concerns during the perioperative period.
      Single ventricle physiology represents a delicate balance between systemic and
      pulmonary blood flow. Any alterations in blood flow through these systems can
      produce undesirable hemodynamic changes, especially during the perioperative
      period. We present a case of an adult patient with a single left ventricle who
      presented for laparoscopic total colectomy due to inflammatory bowel disease. His
      abnormal anatomy coupled with the hemodynamic disruptions caused by laparoscopy
      presented significant anesthetic challenges. We highlight the anesthetic concerns
      of single ventricle physiology, specifically pertaining to laparoscopic surgery.
      We provide recommendations for safely managing these patients perioperatively.
      With detailed preoperative evaluation and close hemodynamic monitoring during the
      perioperative period, these patients can experience successful surgical and
      anesthetic outcomes. 

PMID- 25849704
TI  - Anticoagulation dilemma in a high-risk patient with On-X valves.
AB  - Thromboembolism continues to be a major concern in patients with mechanical heart
      valves, especially in those with unsatisfactory anticoagulation levels. The new
      On-X valve (On-X Life Technologies, Austin, TX, USA) has been reported as having
      unique structural characteristics that offer lower thrombogenicity to the valve.
      We report a case where the patient received no or minimal systemic
      anticoagulation after placement of On-X mitral and aortic valves due to
      development of severe mucosal arterio-venous malformations yet did not show any
      evidence of thromboembolism. This case report reinforces the findings of recent
      studies that lower anticoagulation levels may be acceptable in patients with On-X
      valves and suggests this valve may be particularly useful in those in whom
      therapeutic levels of anticoagulation cannot be achieved due to increased risk of
      bleeding. 

PMID- 25849705
TI  - Combined etiology of anaphylactic cardiogenic shock: amiodarone, epinephrine,
      cardioverter defibrillator, left ventricular assist devices and the Kounis
      syndrome.
AB  - Anaphylactic shock is a life-threatening condition which needs detailed and
      mediculous clinical assessment and thoughtful treatment. Several causes can join
      forces in order to degranulate mast cells. Amiodarone which is an iodine
      containing highly lipophilic benzofuran can induce allergic reactions and
      anaphylactic shock in sensitized patients. Epinephrine is a life saving drug, but
      in sulfite allergic patients it should be given with caution due its
      metabisulfite preservative. Metals covering cardiac defibrillators and pacemakers
      can act as antigens attached to serum proteins and induce allergic reactions. In
      anaphylactic shock, myocardial involvement due to vasospasm-induced coronary
      blood flow reduction manifesting as Kounis syndrome should be always considered.
      Clinically, combined treatment targeting the primary cause of anaphylaxis
      together with protection of cardiac tissue seems to be of paramount importance. 

PMID- 25849706
TI  - Cardiac myxoma: a shadow cast elsewhere.

PMID- 25849707
TI  - Intravenous regional anesthesia as an anesthetic technique for a patient with
      ventricular bigeminy.

PMID- 25849708
TI  - Right main bronchus bulge after capnothorax for thoracoscopic esophagectomy: an
      interesting finding on fiber-optic bronchoscopy through a double lumen tube!

PMID- 25849709
TI  - Malposition of a nasogastric tube.

PMID- 25849710
TI  - Flambeau in the left atrium.

PMID- 25849711
TI  - Entrapped left atrial pressure monitoring catheter in a prosthetic mitral valve.

PMID- 25849712
TI  - Calcium-catalyzed asymmetric synthesis of 3-tetrasubstituted oxindoles: efficient
      construction of adjacent quaternary and tertiary chiral centers.
AB  - Chiral Ca-catalyzed asymmetric addition reactions of 3-substituted oxindoles with
      N-Boc-imines afford 3-tetrasubstituted oxindole derivatives bearing adjacent
      quaternary and tertiary chiral centers, which are key structures for biological
      activities. Ubiquitous and nontoxic Ca catalysts (1-10 mol %) work well in this
      reaction, and high yields (up to 99%) and selectivities (up to >99% ee) of the
      products with wide substrate scope have been attained. The structures of the
      chiral Ca catalysts and intermediary Ca enolates are also discussed. 

PMID- 25849714
TI  - Extraction of crude polysaccharides from Duchesnea indica (Andrews) Focke:
      optimization by response surface methodology.
AB  - A full set of optimization procedure was applied to the extraction of anti-viral
      polysaccharides from Duchesnea indica (Andrews) Focke. By Plackett-Burman
      factorial design, three parameters (extraction time, extraction temperature, and
      ratio of water to raw material) were identified as significant to the extraction
      yield. However, no significant parameters had been identified for antiviral
      activity. A three-level-three-factor Box-Behnken factorial design was then
      employed to further optimize the extraction condition. The experimental data were
      fitted to a second-order polynomial equation using multiple regression analysis
      and also examined using appropriate statistical methods. This led to the
      construction of a response surface indicating the optimal values for each
      parameter and response studied. Concerning the extraction yield, an extraction at
      98.51 oC for 6.16 h with a ratio of water to raw material of 30.94 mL/g was found
      to be optimal. Under the optimized conditions, the experimental yield was 6.430
      +/- 0.078%, which was well matched with the predicted yield of 6.509%.

PMID- 25849715
TI  - Causal effects of time-dependent treatments in older patients with non-small cell
      lung cancer.
AB  - BACKGROUND: Treatment selection for elderly patients with lung cancer must
      balance the benefits of curative/life-prolonging therapy and the risks of
      increased mortality due to comorbidities. Lung cancer trials generally exclude
      patients with comorbidities and current treatment guidelines do not specifically
      consider comorbidities, so treatment decisions are usually made on subjective
      individual-case basis. METHODS: Impacts of surgery, radiation, and chemotherapy
      mono-treatment as well as combined chemo/radiation on one-year overall survival
      (compared to no-treatment) are studied for stage-specific lung cancer in 65+ y.o.
      patients. Methods of causal inference such as propensity score with inverse
      probability weighting (IPW) for time-independent and marginal structural model
      (MSM) for time-dependent treatments are applied to SEER-Medicare data considering
      the presence of comorbid diseases. RESULTS: 122,822 patients with stage I
      (26.8%), II (4.5%), IIIa (11.5%), IIIb (19.9%), and IV (37.4%) lung cancer were
      selected. Younger age, smaller tumor size, and fewer baseline comorbidities
      predict better survival. Impacts of radio- and chemotherapy increased and impact
      of surgery decreased with more advanced cancer stages. The effects of all
      therapies became weaker after adjustment for selection bias, however, the changes
      in the effects were minor likely due to the weak selection bias or incompleteness
      of the list of predictors that impacted treatment choice. MSM provides more
      realistic estimates of treatment effects than the IPW approach for time
      independent treatment. CONCLUSIONS: Causal inference methods provide substantive
      results on treatment choice and survival of older lung cancer patients with
      realistic expectations of potential benefits of specific treatments. Applications
      of these models to specific subsets of patients can aid in the development of
      practical guidelines that help optimize lung cancer treatment based on individual
      patient characteristics.

PMID- 25849716
TI  - Inherent transcriptional signatures of NK cells are associated with response to
      IFNalpha + rivabirin therapy in patients with Hepatitis C Virus.
AB  - BACKGROUND: Differences in the expression of Natural Killer cell receptors have
      been reported to reflect divergent clinical courses in patients with chronic
      infections or tumors. However, extensive molecular characterization at the
      transcriptional level to support this view is lacking. The aim of this work was
      to characterize baseline differences in purified NK cell transcriptional activity
      stratified by response to treatment with PEG-IFNalpha/RBV in patients chronically
      infected with HCV. METHODS: To this end we here studied by flow cytometer and
      gene expression profile, phenotypic and transcriptional characteristics of
      purified NK cells in patients chronically infected with HCV genotype-1 virus who
      were subsequently treated with PEG-IFNalpha/RBV. Results were further correlated
      with divergent clinical response obtained after treatment. RESULTS: The pre
      treatment transcriptional patterns of purified NK cells from patients
      subsequently undergoing a sustained virologic response (SVR) clearly segregated
      from those of non-responder (NR) patients. A set of 476 transcripts, including
      molecules involved in RNA processing, ubiquitination pathways as well as HLA
      class II signalling were differently expressed among divergent patients. In
      addition, treatment outcome was associated with differences in surface expression
      of NKp30 and NKG2D. A complex relationship was observed that suggested for
      extensive post-transcriptional editing. Only a small number of the NK cell
      transcripts identified were correlated with chronic HCV infection/replication
      indicating that inherent transcriptional activity prevails over environment
      effects such as viral infection. CONCLUSIONS: Collectively, inherent/genetic
      modulation of NK cell transcription is involved in setting the path to divergent
      treatment outcomes and could become useful to therapeutic advantage.

PMID- 25849717
TI  - Endoplasmic reticulum stress is increased in adipose tissue of women with
      gestational diabetes.
AB  - Maternal obesity and gestational diabetes mellitus (GDM) are two increasingly
      common and important obstetric complications that are associated with severe long
      term health risks to mothers and babies. IL-1beta, which is increased in obese
      and GDM pregnancies, plays an important role in the pathophysiology of these two
      pregnancy complications. In non-pregnant tissues, endoplasmic (ER) stress is
      increased in diabetes and can induce IL-1beta via inflammasome activation. The
      aim of this study was to determine whether ER stress is increased in omental
      adipose tissue of women with GDM, and if ER stress can also upregulate
      inflammasome-dependent secretion of IL-1beta. ER stress markers IRE1alpha, GRP78
      and XBP-1s were significantly increased in adipose tissue of obese compared to
      lean pregnant women. ER stress was also increased in adipose tissue of women with
      GDM compared to BMI-matched normal glucose tolerant (NGT) women. Thapsigargin, an
      ER stress activator, induced upregulated secretion of mature IL-1alpha and IL
      1beta in human omental adipose tissue explants primed with bacterial endotoxin
      LPS, the viral dsRNA analogue poly(I:C) or the pro-inflammatory cytokine TNF
      alpha. Inhibition of capase-1 with Ac-YVAD-CHO resulted in decreased IL-1alpha
      and IL-1beta secretion, whereas inhibition of pannexin-1 with carbenoxolone
      suppressed IL-1beta secretion only. Treatment with anti-diabetic drugs metformin
      and glibenclamide also reduced IL-1alpha and IL-1beta secretion in infection and
      cytokine-primed adipose tissue. In conclusion, this study has demonstrated ER
      stress to activate the inflammasome in pregnant adipose tissue. Therefore,
      increased ER stress may contribute towards the pathophysiology of obesity in
      pregnancy and GDM. 

PMID- 25849719
TI  - Diagnostics are the vanguard of medicine.

PMID- 25849718
TI  - High seroprevalence for spotted fever group rickettsiae, is associated with
      higher temperatures and rural environment in Mbeya region, Southwestern Tanzania.
AB  - BACKGROUND: Rickettsioses are endemic in sub-Sahara Africa. Burden of disease,
      risk factors and transmission are hitherto sparsely described. METHODS: From the
      EMINI (Evaluating and Monitoring the Impact of New Interventions) population
      cohort, we randomly selected 1,228 persons above the age of 5 years from the nine
      participating communities in Mbeya region, Southwestern Tanzania, stratified by
      age, altitude of residence and ownership of domestic mammals, to conduct a cross
      sectional seroprevalence study in. The aim was to estimate the seroprevalence of
      IgG antibodies against Spotted Fever Group (SFG) rickettsiae and to assess
      socioeconomic and environmental risk factors. Serology (indirect
      immunofluorescence) was performed at a dilution of 1:64. RESULTS: SFG
      seropositivity in the cohort was found to be 67.9% (range among nine sites: 42.8
      91.4%). Multivariable analysis revealed an association with age (prevalence
      ratio, PR per 10 years: 1.08; 95% CI 1.06-1.10), warmer temperatures (PR per 
      degrees C: 1.38; 1.11-1.71), male gender (PR 1.08; 1.00-1.16), and low population
      density (PR per 1.000 persons/km2increase 0.96; 0.94-0.99). At higher elevations,
      higher cattle density was associated with higher seroprevalence. CONCLUSION: SFG
      rickettsial infection seems to be common in the more rural population of Mbeya
      Region. Spread seems to be further limited by temperature and higher elevation.
      Examination of the contribution of SFG to febrile illnesses seems warranted in a
      prospective study to estimate the disease burden in the population. This will
      also allow determination of the causative pathogens.

PMID- 25849720
TI  - Participating in next generation sequencing.

PMID- 25849722
TI  - Robust molecular bowl-based metal-organic frameworks with open metal sites: size
      modulation to increase the catalytic activity.
AB  - Herein, two stable lead(II) molecular-bowl-based metal-organic frameworks and
      their micro- and nanosized forms with open metal sites were presented. These
      materials could act as Lewis acid catalysts to cyanosilylation reaction.
      Moreover, the catalytic performances are size-dependent, with the catalyst with
      nanosized form being 1 order of magnitude more efficient than those with micro-
      and millisized forms. 

PMID- 25849721
TI  - Changes in insulin receptor signaling underlie neoadjuvant metformin
      administration in breast cancer: a prospective window of opportunity neoadjuvant
      study.
AB  - INTRODUCTION: The antidiabetic drug metformin exhibits potential anticancer
      properties that are believed to involve both direct (insulin-independent) and
      indirect (insulin-dependent) actions. Direct effects are linked to activation of
      AMP-activated protein kinase (AMPK) and an inhibition of mammalian target of
      rapamycin mTOR signaling, and indirect effects are mediated by reductions in
      circulating insulin, leading to reduced insulin receptor (IR)-mediated signaling.
      However, the in vivo impact of metformin on cancer cell signaling and the factors
      governing sensitivity in patients remain unknown. METHODS: We conducted a
      neoadjuvant, single-arm, "window of opportunity" trial to examine the clinical
      and biological effects of metformin on patients with breast cancer. Women with
      untreated breast cancer who did not have diabetes were given 500 mg of metformin
      three times daily for >=2 weeks after diagnostic biopsy until surgery. Fasting
      blood and tumor samples were collected at diagnosis and surgery. Blood glucose
      and insulin were assayed to assess the physiologic effects of metformin, and
      immunohistochemical analysis of tumors was used to characterize cellular markers
      before and after treatment. RESULTS: Levels of IR expression decreased
      significantly in tumors (P = 0.04), as did the phosphorylation status of protein
      kinase B (PKB)/Akt (S473), extracellular signal-regulated kinase 1/2 (ERK1/2,
      T202/Y204), AMPK (T172) and acetyl coenzyme A carboxylase (S79) (P = 0.0001, P <
      0.0001, P < 0.005 and P = 0.02, respectively). All tumors expressed organic
      cation transporter 1, with 90% (35 of 39) exhibiting an Allred score of 5 or
      higher. CONCLUSIONS: Reduced PKB/Akt and ERK1/2 phosphorylation, coupled with
      decreased insulin and IR levels, suggest insulin-dependent effects are important
      in the clinical setting. These results are consistent with beneficial anticancer
      effects of metformin and highlight key factors involved in sensitivity, which
      could be used to identify patients with breast cancer who may be responsive to
      metformin-based therapies. TRIAL REGISTRATION: ClinicalTrials.gov identifier:
      NCT00897884. Registered 8 May 2009.

PMID- 25849723
TI  - Matrix metalloproteinase-9 expression is enhanced in renal parietal epithelial
      cells of zucker diabetic Fatty rats and is induced by albumin in in vitro primary
      parietal cell culture.
AB  - As a subfamily of matrix metalloproteinases (MMPs), gelatinases including MMP-2
      and MMP-9 play an important role in remodeling and homeostasis of the
      extracellular matrix. However, conflicting results have been reported regarding
      their expression level and activity in the diabetic kidney. This study
      investigated whether and how MMP-9 expression and activity were changed in
      glomerular epithelial cells upon albumin overload. In situ zymography,
      immunostaining and Western blot for renal MMP gelatinolytic activity and MMP-9
      protein expression were performed in Zucker lean and Zucker diabetic rats.
      Confocal microscopy revealed a focal increase in gelatinase activity and MMP-9
      protein in the glomeruli of diabetic rats. Increased glomerular MMP-9 staining
      was mainly observed in hyperplastic parietal epithelial cells (PECs) expressing
      claudin-1 in the diabetic kidneys. Interestingly, increased parietal MMP-9 was
      often accompanied by decreased staining for podocyte markers (nephrin and
      podocalyxin) in the sclerotic area of affected glomeruli in diabetic rats.
      Additionally, urinary excretion of podocyte marker proteins was significantly
      increased in association with the levels of MMP-9 and albumin in the urine of
      diabetic animals. To evaluate the direct effect of albumin on expression and
      activity of MMP-9, primary cultured rat glomerular PECs were incubated with rat
      serum albumin (0.25 - 1 mg/ml) for 24 - 48 hrs. MMP-9 mRNA levels were
      significantly increased following albumin treatment. Meanwhile, albumin
      administration resulted in a dose-dependent increase in MMP-9 protein and
      activity in culture supernatants of PECs. Moreover, albumin activated p44/42
      mitogen-activated protein kinase (MAPK) in PECs. Inhibition of p44/42 MAPK
      suppressed albumin-induced MMP-9 secretion from glomerular PECs. Taken together,
      we have demonstrated that an up-regulation of MMP-9 in activated parietal
      epithelium is associated with a loss of adjacent podocytes in progressive
      diabetic nephropathy. Albumin overload may induce MMP-9 expression and secretion
      by PECs via the activation of p44/42 MAPK pathway. 

PMID- 25849725
TI  - High-throughput, quantitative enzyme kinetic analysis in microdroplets using
      stroboscopic epifluorescence imaging.
AB  - Droplet-based microfluidic systems offer a range of advantageous features for the
      investigation of enzyme kinetics, including high time resolution and the ability
      to probe extremely large numbers of discrete reactions while consuming low sample
      volumes. Kinetic measurements within droplet-based microfluidic systems are
      conventionally performed using single point detection schemes. Unfortunately,
      such an approach prohibits the measurement of an individual droplet over an
      extended period of time. Accordingly, we present a novel approach for the
      extensive characterization of enzyme-inhibitor reaction kinetics within a single
      experiment by tracking individual and rapidly moving droplets as they pass
      through an extended microfluidic channel. A series of heterogeneous and pL-volume
      droplets, containing varying concentrations of the fluorogenic substrate
      resorufin beta-d-galactopyranoside and a constant amount of the enzyme beta
      galactosidase, is produced at frequencies in excess of 150 Hz. By stroboscopic
      manipulation of the excitation laser light and adoption of a dual view detection
      system, "blur-free" images containing up to 150 clearly distinguishable droplets
      per frame are extracted, which allow extraction of kinetic data from all formed
      droplets. The efficiency of this approach is demonstrated via a Michaelis-Menten
      analysis which yields a Michaelis constant, Km, of 353 MUM. Additionally, the
      dissociation constant for the competitive inhibitor isopropyl beta-d-1
      thiogalactopyranoside is extracted using the same method. 

PMID- 25849724
TI  - TASK-1 Potassium Channels Limit Pancreatic alpha-Cell Calcium Influx and Glucagon
      Secretion.
AB  - Glucose regulation of pancreatic alpha-cell Ca(2+) entry through voltage
      dependent Ca(2+) channels is essential for normal glucagon secretion and becomes
      defective during the pathogenesis of diabetes mellitus. The 2-pore domain K(+)
      channel, TWIK-related acid-sensitive K(+) channel 1 (TASK-1), is an important
      modulator of membrane voltage and Ca(2+) entry. However, its role in alpha-cells
      has not been determined. Therefore, we addressed how TASK-1 channels regulate
      alpha-cell electrical activity, Ca(2+) entry, and glucagon secretion. We find
      that TASK-1 channels expressed in human and rodent alpha-cells are blocked by the
      TASK-1 channel inhibitor A1899. Alpha-cell 2-pore domain K(+) currents were also
      significantly reduced after ablation of mouse alpha-cell TASK-1 channels.
      Inhibition of TASK-1 channels with A1899 caused plasma membrane potential
      depolarization in both human and mouse alpha-cells, which resulted in increased
      electrical excitability. Moreover, ablation of alpha-cell TASK-1 channels
      increased alpha-cell electrical excitability under elevated glucose (11 mM)
      conditions compared with control alpha-cells. This resulted in significantly
      elevated alpha-cell Ca(2+) influx when TASK-1 channels were inhibited in the
      presence of high glucose (14 mM). However, there was an insignificant change in
      alpha-cell Ca(2+) influx after TASK-1 inhibition in low glucose (1 mM). Glucagon
      secretion from mouse and human islets was also elevated specifically in high (11
      mM) glucose after acute TASK-1 inhibition. Interestingly, mice deficient for
      alpha-cell TASK-1 showed improvements in both glucose inhibition of glucagon
      secretion and glucose tolerance, which resulted from the chronic loss of alpha
      cell TASK-1 currents. Therefore, these data suggest an important role for TASK-1
      channels in limiting alpha-cell excitability and glucagon secretion during
      glucose stimulation.

PMID- 25849726
TI  - Lung inflammatory pattern and antibiotic treatment in pneumonia.
AB  - BACKGROUND: In community-acquired pneumonia host inflammatory response against
      the causative microorganism is necessary for infection resolution. However an
      excessive response can have deleterious effects. In addition to antimicrobial
      effects, macrolide antibiotics are known to possess immunomodulatory properties.
      METHODS: A prospective study was performed on 52 admitted patients who developed
      an inadequate response after 72 hours of antibiotic treatment - non-responders
      community-acquired pneumonia - (blood and bronchoalveolar lavage), and two
      control groups: 1) community-acquired pneumonia control (blood) and 2) non
      infection control (blood and bronchoalveolar lavage). Cytokine profiles
      (interleukin (IL)-6, IL-8, IL-10), tumour necrosis factor alpha and clinical
      outcomes were assessed. RESULTS: Non-responders patients treated with macrolide
      containing regimens showed significantly lower levels of IL-6 and TNF-alpha in
      bronchoalveolar lavage fluid and lower IL-8 and IL-10 in blood than those
      patients treated with non-macrolide regimens. Clinical outcomes showed that
      patients treated with macrolide regimens required fewer days to reach clinical
      stability (p < 0.01) and shorter hospitalization periods (p < 0.01). CONCLUSIONS:
      After 72 hours of antibiotic effect, patients who received macrolide containing
      regimens exhibited lower inflammatory cytokine levels in pulmonary and systemic
      compartments along with faster stabilization of infectious parameters.

PMID- 25849727
TI  - GnRH Regulates Gonadotropin Gene Expression Through NADPH/Dual Oxidase-Derived
      Reactive Oxygen Species.
AB  - The appropriate control of synthesis and secretion of the gonadotropin hormones
      LH and FSH by pituitary gonadotropes is essential for the regulation of
      reproduction. The hypothalamic neuropeptide GnRH is the central regulator of both
      processes, coordinating secretion with transcription and translation of the
      gonadotropin hormone subunit genes. The MAPK family of second messengers is
      strongly induced in gonadotropes upon GnRH stimulation, and multiple pathways
      activate these kinases. Intracellular reactive oxygen species participate in
      signaling cascades that target MAPKs, but also participate in signaling events
      indicative of cell stress. The NADPH oxidase (NOX)/dual oxidase (DUOX) family is
      a major enzymatic source of intracellular reactive oxygen, and we show that GnRH
      stimulation of mouse primary pituitary cells and the LbetaT2 gonadotrope cell
      line elevates intracellular reactive oxygen via NOX/DUOX activity. Mouse
      pituitary and LbetaT2 cells abundantly express NOX/DUOX and cofactor mRNAs.
      Pharmacological inhibition of NOX/DUOX activity diminishes GnRH-stimulated
      activation of MAPKs, immediate-early gene expression, and gonadotropin subunit
      gene expression. Inhibitor studies implicate the calcium-activated DUOX family as
      a major, but not exclusive, participant in GnRH signaling. Knockdown of DUOX2 in
      LbetaT2 cells reduces GnRH-induced Fshb, but not Lhb mRNA levels, suggesting
      differential sensitivity to DUOX activity. Finally, GnRH pulse-stimulated FSH and
      LH secretion are suppressed by inhibition of NOX/DUOX activity. These results
      indicate that reactive oxygen is a potent signaling intermediate produced in
      response to GnRH stimulation and further suggest that reactive oxygen derived
      from other sources may influence the gonadotrope response to GnRH stimulation. 

PMID- 25849729
TI  - Oocyte induction of EGF responsiveness in somatic cells is associated with the
      acquisition of porcine oocyte developmental competence.
AB  - Oocytes progressively acquire the competence to support embryo development as
      oogenesis proceeds with ovarian folliculogenesis. The objectives of this study
      were to investigate oocyte-secreted factor (OSF) participation in the development
      of somatic cell epidermal growth factor (EGF) responsiveness associated with
      oocyte developmental competence. A well-established porcine model was employed
      using oocytes from small (<4 mm) vs medium sized (>4 mm) antral follicles,
      representing low vs moderate developmental competence, respectively. Cumulus
      oocyte complexes (COCs) were treated in vitro with inducers of oocyte maturation,
      and cumulus cell functions and oocyte developmental competence were assessed.
      COCs from small follicles responded to FSH but, unlike COCs from larger
      follicles, were incapable of responding to EGF family growth factors known to
      mediate oocyte maturation in vivo, exhibiting perturbed cumulus expansion and
      expression of associated transcripts (HAS2 and TNFAIP6). Low and moderate
      competence COCs expressed equivalent levels of EGF receptor (EGFR) mRNA; however,
      the former had less total EGFR protein leading to failed activation of phospho
      EGFR and phospho-ERK1/2, despite equivalent total ERK1/2 protein levels. Native
      OSFs from moderate, but not from low, competence oocytes established EGF
      responsiveness in low competence COCs. Four candidate recombinant OSFs failed to
      mimic the actions of native OSFs in regulating cumulus expansion. Treatment with
      OSFs and EGF enhanced oocyte competence but only of the low competence COCs.
      These data suggest that developmental acquisition by the oocyte of capacity to
      regulate EGF responsiveness in the oocyte's somatic cells is a major milestone in
      the oocyte's developmental program and contributes to coordinated oocyte and
      somatic cell development. 

PMID- 25849728
TI  - CYP7B1 Enzyme Deletion Impairs Reproductive Behaviors in Male Mice.
AB  - In addition to androgenic properties mediated via androgen receptors,
      dihydrotestosterone (DHT) also regulates estrogenic functions via an alternate
      pathway. These estrogenic functions of DHT are mediated by its metabolite 5alpha
      androstane-3beta, 17beta-diol (3beta-diol) binding to estrogen receptor beta
      (ERbeta). CYP7B1 enzyme converts 3beta-diol to inactive 6alpha- or 7alpha-triols
      and plays an important role as a regulator of estrogenic functions mediated by
      3beta-diol. Using a mutant mouse carrying a null mutation for the CYP7B1 gene
      (CYP7B1KO), we examined the contribution of CYP7B1 on physiology and behavior.
      Male, gonadectomized (GDX) CYP7B1KO and their wild type (WT) littermates were
      assessed for their behavioral phenotype, anxiety-related behavioral measures, and
      hypothalamic pituitary adrenal axis reactivity. No significant effects of
      genotype were evident in anxiety-like behaviors in open field (OFA), light-dark
      (L/D) exploration, and elevated plus maze (EPM). T significantly reduced open arm
      time on the EPM while not affecting L/D exploratory and OFA behaviors in CYP7B1KO
      and WT littermates. T also attenuated the corticosterone response to EPM in both
      genotypes. In GDX animals, T was able to reinstate male-specific reproductive
      behaviors (latencies and number of mounts, intromission, and ejaculations) in the
      WT but not in the CYP7B1KO mice. The male reproductive behavior defect in
      CYP7B1KO seems to be due to their inability to distinguish olfactory cues from a
      behavioral estrus female. CYP7B1KO mice also showed a reduction in androgen
      receptor mRNA expression in the olfactory bulb. Our findings suggest a novel role
      for the CYP7B1 enzyme in the regulation of male reproductive behaviors. 

PMID- 25849731
TI  - Determinants of suboptimal breastfeeding practices in Nigeria: evidence from the
      2008 demographic and health survey.
AB  - BACKGROUND: In Nigeria, suboptimal breastfeeding practices are contributing to
      the burden of childhood diseases and mortality. This study identified the
      determinants of key suboptimal breastfeeding practices among children 0-23 months
      in Nigeria. METHOD: Data on 10,225 children under-24 months were obtained from
      the 2008 Nigeria Demographic and Health Survey (NDHS). Socio-economic, health
      service and individual factors associated with key breastfeeding indicators
      (early initiation of breastfeeding, exclusive breastfeeding, predominant
      breastfeeding and bottle feeding) were investigated using multiple logistic
      regression analyses. RESULTS: Among infants 0-5 months of age, 14% [95%
      confidence Interval (CI): 13%, 15%] were exclusively breastfed and 48% [95% CI:
      46, 50%] were predominantly breastfed. Among children aged 0-23 months, 38% [95%
      CI 36, 39%] were breastfed within the first hour of birth, and 15% [95% CI: 14,
      17%] were bottle-fed. Early initiation of breastfeeding was associated with
      higher maternal education, frequent antenatal care (ANC) visits and birth
      interval but deliveries at a health facility with caesarean section was
      associated with delayed initiation of breastfeeding. Educated mothers, older
      mothers and mothers from wealthier households exclusively breastfeed their
      babies. The risk for bottle feeding was higher among educated mothers and
      fathers, and women from wealthier households including mothers who made frequent
      ANC visits. CONCLUSION: Socio-economic and health service factors were associated
      with suboptimal breastfeeding practices in Nigeria. To improve the current
      breastfeeding practices, breastfeeding initiatives should target all mothers -
      particularly low SES mothers - including, national and sub-national health
      policies that ensure improved access to maternal health services, and
      improvements to baby friendly hospital and community initiatives for mothers.

PMID- 25849732
TI  - Trillium tschonoskii steroidal saponins suppress the growth of colorectal Cancer
      cells in vitro and in vivo.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Saponins of many herbs are known to possess anti
      cancer effect. AIM OF THE STUDY: The present study aimed to investigate the
      growth inhibitory effect of Trillium tschonoskii steroidal saponins in a mouse
      model of colitis-associated colorectal cancer and a human colorectal cancer cell
      line HT-29, and isolate some major constituents and evaluate their anti-tumor
      activity. MATERIALS AND METHODS: Forty male ICR mice were administered with 1, 2
      dimethyl-hydrazine (DMH) and dextran sodium sulfate (DSS). Ten mice were given no
      further treatment, the rest were administered with different doses of TTS (5, 10,
      20mg/kg) orally, every three days from the 9th week to the 20th week. RESULTS:
      TTS effectively protected ICR mice against DMH/DSS-induced tumorigenesis. The
      incidence of tumor development was 90% (9/10) in the mice treated with DMH/DSS,
      but that was reduced to 50% (5/10), 40% (4/10), and 20% (2/10), respectively, in
      the mice treated with 5%, 10%, and 20% of TTS. Results of Ki-67 staining, TUNEL
      assay and caspase-3 activity assay revealed that TTS moderately decreased
      abnormal proliferation and increased apoptosis of colonic epithelial cells. It
      inhibited the growth and triggered the apoptosis of HT-29 cells, partly through
      suppressing mitogen-actived protein kinases (MAPKs) and triggering mitochondrial
      mediated apoptotic pathway. Three compounds, namely, Paris saponin VII,
      polyphylloside III and Paris saponin VI, were important active compounds in TTS.
      CONCLUSION: These data suggest that TTS has a potential role in clinical
      prevention and treatment for colorectal cancer.

PMID- 25849733
TI  - In vivo estrogenic-like activities of Gouania longipetala Hemsl. (Rhamnaceae)
      bark extracts in a post-menopause-like model of ovariectomized Wistar rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Gouania longipetala is commonly used in
      Cameroonian traditional medicine to manage women fertility and menopausal
      complaints. However, despite this use, the estrogenic properties of G.
      longipetala have not been studied until now. AIM OF STUDY: The present study was
      aimed to assess estrogenic activities of the stem bark aqueous (GLA) and
      ethanolic (GLE) extracts of G. longipetala in post-menopause-like model of
      ovariectomized (Ovx) Wistar rats. MATERIAL AND METHODS: Animals were either sham
      operated or Ovx. 84 days after ovariectomy, animals were divided into seven
      groups of five animals and were daily treated for 28 days with distilled water
      (10 mL/kg) for group 1, 2% solution of Tween 80 (10 mL/kg) for group 2, estradiol
      valerate (1 mg/kg) for group 3, GLA (45 or 180 mg/kg) and GLE (40 or 160 mg/kg)
      for groups 4 to 7 respectively. Sham-operated animals daily received distilled
      water (10 mL/kg). During the experimental period, the body weight was registered
      every week. At the day 29, blood pressure was registered by invasive method while
      uterine and vagina morphometry as well as body, uterine and abdominal fat weights
      changes were analyzed. Serum levels of total cholesterol, triglycerides, HDL
      cholesterol and LDL-cholesterol were determined. Moreover, oxidative stress
      markers such as nitrites, reduced glutathione (GSH) and malondialdehyde (MDA)
      were measured in homogenized liver and aorta. RESULTS: Compared with the sham
      control, vagina and uterine dystrophy and elevated blood pressure were observed
      in Ovx rats treated with vehicles. Biochemical parameters showed a significant
      increase of total cholesterol, triglycerides, LDL-cholesterol and MDA as well as
      a significant decrease of nitrites and GSH in Ovx animals treated with vehicle as
      compared to sham group. GLA and GLE displayed estrogen-like effects on vagina and
      did not affect uterine wet weight and epithelial height compared with vehicle
      groups. Both extracts displayed anti-atherogenic properties by reducing AI, AIP
      and LDL-cholesterol level as compared to vehicles groups. GLA and GLE
      significantly prevented the increase of MDA induced by ovariectomy as compared to
      rats treated with vehicles. CONCLUSION: This study showed that GLA and GLE
      exhibited estrogenic effects by providing vaginal lubrication, by modulating
      blood pressure and improving lipid profile, oxidative status and endothelial
      function and may not have an undesirable influence on the endometrium in
      ovariectomized rats.

PMID- 25849734
TI  - Yinchenhao decoction in the treatment of cholestasis: A systematic review and
      meta-analysis.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Yinchenhao decoction, a well-known Chinese herbal
      formula, has been widely used in Chinese Medicine for thousands of years.
      However, no systematic review of Yinchenhao decoction in treating cholestasis has
      been completed. This study aims to evaluate the efficacy and safety of the
      Yinchenhao decoction in treating cholestasis. MATERIALS AND METHODS: The major
      databases (PubMed, Embase, Cochrane Library, Chinese Biomedical Database, Wanfang
      database, VIP medicine information system and China National Knowledge
      Infrastructure) were searched from the databases' inception through November
      2014. Randomized controlled trials (RCTs) of Yinchenhao decoction reported in
      publications for treatment of cholestasis were extracted by two reviewers. The
      RCTs examined included total efficacy rate and biochemical indices including
      alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin
      (TBIL) and direct bilirubin (DBIL). The Cochrane tool was applied to assess the
      risk of bias of the trials. The main outcomes of the trials were analyzed using
      Review Manager 5.3 software. The odds ratio (OR) or mean difference (MD) with a
      95% confidence interval (CI) was used to measure the effect. RESULTS: Among the
      698 studies identified in the literature search, 15 studies involving 1405
      subjects with cholestasis were included in the analysis. Yinchenhao decoction
      demonstrated efficacy in cholestasis treatment whether in a combined application
      or not. Additionally, the decoction significantly reduced the elevated levels of
      cholestasis serum markers, such as ALT, AST, TBIL and DBIL, with a significant
      difference observed in short and long curative time periods. Remarkably,
      Yinchenhao decoction displayed a significant efficacy in treating the long-term
      disease. CONCLUSION: No serious adverse event was reported. This meta-analysis
      provides evidence that Yinchenhao decoction is an effective and safe treatment
      for cholestasis.

PMID- 25849735
TI  - Moderately increased albuminuria is an independent risk factor of cardiovascular
      events in the general Japanese population under 75 years of age: the Watari
      study.
AB  - BACKGROUND: Moderately increased albuminuria (formerly called microalbuminuria)
      is widely recognized as a predictor of cardiovascular disease. However, it is not
      clear whether this observation is applicable to the Asian population, as studies
      leading to this conclusion were conducted on Western populations. The aim of this
      study was to examine the hypothesis if moderately increased albuminuria could be
      an independent predictor of cardiovascular mortality and morbidity in the
      Japanese population. METHODS AND RESULTS: The study population consisted of 3093
      inhabitants of Watari, Miyagi Prefecture, who participated in an annual health
      check-up in 2009. We examined anthropometry, sitting blood pressure, fasting
      blood sample, and urine albumin-to-creatinine ratio (UACR). After baseline
      assessment, subjects were followed prospectively for up to 60 months. The
      incidence of major cardiovascular events (stroke, myocardial infarction,
      revascularization, and cardiovascular death) was determined based on death
      certificate records or medical claims sent to the National Health Insurance of
      Japan. Follow-up was discontinued for those who reached 75 years of age because
      they were moved to a different medical insurance system. We observed 57
      cardiovascular events during a mean follow-up period of 47.8 months. The
      cumulative incidence rate for major cardiovascular events was significantly
      higher in patients with moderately increased albuminuria (UACR 30-299 mg/gCr)
      than in those with normoalbuminuria (UACR <30 mg/gCr) (6.4% vs. 2.2%, p = 0.0002
      by log-rank test). Multivariate Cox proportional hazards analyses have revealed
      that moderately increased albuminuria is an independent predictor of
      cardiovascular events (HR 2.386, 95% CI: 1.120-4.390). CONCLUSIONS: Moderately
      increased albuminuria is an independent predictor of cardiovascular events in the
      general Japanese population under 75 years of age.

PMID- 25849736
TI  - Correction: evaluation of intradural stimulation efficiency and selectivity in a
      computational model of spinal cord stimulation.

PMID- 25849737
TI  - Network Modularity is essential for evolution of cooperation under uncertainty.
AB  - Cooperative behavior, which pervades nature, can be significantly enhanced when
      agents interact in a structured rather than random way; however, the key
      structural factors that affect cooperation are not well understood. Moreover, the
      role structure plays with cooperation has largely been studied through observing
      overall cooperation rather than the underlying components that together shape
      cooperative behavior. In this paper we address these two problems by first
      applying evolutionary games to a wide range of networks, where agents play the
      Prisoner's Dilemma with a three-component stochastic strategy, and then analyzing
      agent-based simulation results using principal component analysis. With these
      methods we study the evolution of trust, reciprocity and forgiveness as a
      function of several structural parameters. This work demonstrates that community
      structure, represented by network modularity, among all the tested structural
      parameters, has the most significant impact on the emergence of cooperative
      behavior, with forgiveness showing the largest sensitivity to community
      structure. We also show that increased community structure reduces the dispersion
      of trust and forgiveness, thereby reducing the network-level uncertainties for
      these two components; graph transitivity and degree also significantly influence
      the evolutionary dynamics of the population and the diversity of strategies at
      equilibrium. 

PMID- 25849738
TI  - Controlling band alignments by artificial interface dipoles at perovskite
      heterointerfaces.
AB  - The concept 'the interface is the device' is embodied in a wide variety of
      interfacial electronic phenomena and associated applications in oxide materials,
      ranging from catalysts and clean energy systems to emerging multifunctional
      devices. Many device properties are defined by the band alignment, which is often
      influenced by interface dipoles. On the other hand, the ability to purposefully
      create and control interface dipoles is a relatively unexplored degree of freedom
      for perovskite oxides, which should be particularly effective for such ionic
      materials. Here we demonstrate tuning the band alignment in perovskite metal
      semiconductor heterojunctions over a broad range of 1.7 eV. This is achieved by
      the insertion of positive or negative charges at the interface, and the resultant
      dipole formed by the induced screening charge. This approach can be broadly used
      in applications where decoupling the band alignment from the constituent work
      functions and electron affinities can enhance device functionality. 

PMID- 25849739
TI  - Synthesis, Characterization, and Sunlight Mediated Photocatalytic Activity of CuO
      Coated ZnO for the Removal of Nitrophenols.
AB  - CuO@ZnO core-shell catalysts, coated by varying the CuO layer density ranging
      from 0.5% to 10%, were synthesized with the aim to enhance the photocatalytic
      activity of ZnO in sunlight and control its photocorrosion. Initially, the Cu(2+)
      ions were impregnated on presynthesized ZnO by wet impregnation and finally
      converted to CuO layers by calcination. The optical and structural
      characterization of the synthesized powders was performed by DRS, PL, Raman
      spectroscopy, and XRD analysis, respectively. The homogeneity of the coated
      layers was explored by FESEM. The photocatalytic activity of CuO coated ZnO was
      investigated for the degradation of mononitrophenols (2-, 3-, and 4-nitrophenol)
      and dinitrophenols (2,4-, 2,5-, and 2,6-dinitrophenol) in the exposure of the
      complete spectrum and visible region (420-800 nm) of sunlight. The effect of the
      increasing density coated layers of CuO on photocatalytic activity was evaluated
      for the degradation of 4-NP. Compared to pristine ZnO, a substantial increase in
      the degradation/mineralization ability was observable for the catalysts coated
      with 0.5% and 1% CuO, whereas a detrimental effect was noticed for higher coating
      density. Prior to photocatalytic studies, as evaluated by cyclic voltammetry
      (CV), compared to pure ZnO, a significant suppression of photocorrosion was
      noticed, under illumination, for catalysts coated with lower CuO coating. The
      progress of the photocatalytic degradation process was monitored by HPLC while
      the mineralization ability of the synthesized catalysts was estimated by TOC. The
      estimation of the released ions and their further interaction with the excited
      states and the reactive oxygen was monitored by ion chromatography (IC). 

PMID- 25849740
TI  - Lpr-induced systemic autoimmunity is unaffected by mast cell deficiency.
AB  - The function of mast cells in allergic and organ-specific autoimmune responses is
      highly controversial. In the current study, we aimed to dissect the role of mast
      cells in systemic autoimmunity in the B6(lpr/lpr) mouse, a spontaneous model of
      systemic lupus erythematosus. B6(lpr/lpr) mice were interbred with C57Bl/6-Kit(W
      sh/W-sh) (Wsh) mice, resulting in mast cell deficiency. The offspring from this
      cross (Lpr/Wsh mice) developed symptoms of lupus of the same severity as
      B6(lpr/lpr) mice. Loss of mast cells on the Lpr background did not alter
      autoantibody production, proteinuria, the composition of T and B cell populations
      or autoimmune pathology. Reduced c-Kit expression did drive expanded splenomegaly
      and impeded interleukin-4 production by CD4(+) cells, suggesting minor functions
      for mast cells. In general, we conclude that mast cell deficiency and c-Kit
      deficiency do not play a role in the pathogenesis of lupus in B6(lpr/lpr) mice. 

PMID- 25849741
TI  - Quantitative analysis of the TNF-alpha-induced phosphoproteome reveals AEG
      1/MTDH/LYRIC as an IKKbeta substrate.
AB  - The inhibitor of the nuclear factor-kappaB (IkappaB) kinase (IKK) complex is a
      key regulator of the canonical NF-kappaB signalling cascade and is crucial for
      fundamental cellular functions, including stress and immune responses. The
      majority of IKK complex functions are attributed to NF-kappaB activation;
      however, there is increasing evidence for NF-kappaB pathway-independent
      signalling. Here we combine quantitative mass spectrometry with random forest
      bioinformatics to dissect the TNF-alpha-IKKbeta-induced phosphoproteome in MCF-7
      breast cancer cells. In total, we identify over 20,000 phosphorylation sites, of
      which ~1% are regulated up on TNF-alpha stimulation. We identify various
      potential novel IKKbeta substrates including kinases and regulators of cellular
      trafficking. Moreover, we show that one of the candidates, AEG-1/MTDH/LYRIC, is
      directly phosphorylated by IKKbeta on serine 298. We provide evidence that
      IKKbeta-mediated AEG-1 phosphorylation is essential for IkappaBalpha degradation
      as well as NF-kappaB-dependent gene expression and cell proliferation, which
      correlate with cancer patient survival in vivo. 

PMID- 25849742
TI  - Defective pericyte recruitment of villous stromal vessels as the possible
      etiologic cause of hydropic change in complete hydatidiform mole.
AB  - The pathogenetic mechanism underlying the hydropic change in complete
      hydatidiform moles (CHMs) is poorly understood. A growing body of data suggests
      that pericytes play a role in vascular maturation. Since maturation of villous
      stromal vessels in CHMs is markedly impaired at early stages, we postulated that
      a defect in pericytes around stromal vessels in chorionic villi might cause
      vascular immaturity and subsequent hydropic change. To investigate this, we
      examined several markers of pericytes, namely, alpha-smooth muscle actin (alpha
      SMA), platelet-derived growth factor receptor-beta (PDGFR-beta), and desmin, in
      61 normally developing placentas and 41 CHMs with gestational ages of 4-12 weeks.
      The ultrastructure of villous stromal vessels was also examined. Mature blood
      vessels from normal placentas show patent vascular lumens and formed
      hematopoietic components in the villous stroma. alpha-SMA and PDGFR-beta
      expression in the villous stroma gradually increased and extended from the
      chorionic plate to peripheral villous branches. The labeled cells formed a
      reticular network in the villous stroma and, after week 7, encircled villous
      stromal vessels. In comparison, alpha-SMA and PDGFR-beta expression in the
      villous stroma and stromal vessels of CHMs was significantly lower (p<0.05).
      Ultrastructurally, endothelial cells in villous stromal vessels in normal
      placentas were consistently attached by pericytes after week 7 when the vessels
      formed distinct lumen, whereas the villous stromal vessels in CHMs consisted of
      linear chains of endothelial cells, often disclosing primitive clefts without
      hematopoietic cells inside, and neither pericytes nor basal lamina surrounded the
      endothelial cells at any gestational age studied. This suggests that pericytes
      recruitment around villous stromal vessels is defective in CHMs and links to the
      persistent vascular immaturity of the villous stroma in CHMs, which in turns
      leads to hydropic villi. 

PMID- 25849743
TI  - Iron metallodrugs: stability, redox activity and toxicity against Artemia salina.
AB  - Iron metallodrugs comprise mineral supplements, anti-hypertensive agents and,
      more recently, magnetic nanomaterials, with both therapeutic and diagnostic
      roles. As biologically-active metal compounds, concern has been raised regarding
      the impact of these compounds when emitted to the environment and associated
      ecotoxicological effects for the fauna. In this work we assessed the relative
      stability of several iron compounds (supplements based on glucoheptonate, dextran
      or glycinate, as well as 3,5,5-trimethylhexanoyl (TMH) derivatives of ferrocene)
      against high affinity models of biological binding, calcein and aprotransferrin,
      via a fluorimetric method. Also, the redox-activity of each compound was
      determined in a physiologically relevant medium. Toxicity toward Artemia salina
      at different developmental stages was measured, as well as the amount of lipid
      peroxidation. Our results show that polymer-coated iron metallodrugs are stable,
      non-redox-active and non-toxic at the concentrations studied (up to 300 uM).
      However, TMH derivatives of ferrocene were less stable and more redox-active than
      the parent compound, and TMH-ferrocene displayed toxicity and lipid peroxidation
      to A. salina, unlike the other compounds. Our results indicate that iron
      metallodrugs based on polymer coating do not present direct toxicity at low
      levels of emission; however other iron species (eg. metallocenes), may be
      deleterious for aquatic organisms. We suggest that ecotoxicity depends more on
      metal speciation than on the total amount of metal present in the metallodrugs.
      Future studies with discarded metallodrugs should consider the chemical
      speciation of the metal present in the composition of the drug. 

PMID- 25849744
TI  - Improved Escherichia coli Bactofection and Cytotoxicity by Heterologous
      Expression of Bacteriophage PhiX174 Lysis Gene E.
AB  - Bactofection offers a gene delivery option particularly useful in the context of
      immune modulation. The bacterial host naturally attracts recognition and cellular
      uptake by antigen presenting cells (APCs) as the initial step in triggering an
      immune response. Moreover, depending on the bacterial vector, molecular biology
      tools are available to influence and/or overcome additional steps and barriers to
      effective antigen presentation. In this work, molecular engineering was applied
      using Escherichia coli as a bactofection vector. In particular, the bacteriophage
      PhiX174 lysis E (LyE) gene was designed for variable expression across strains
      containing different levels of lysteriolysin O (LLO). The objective was to
      generate a bacterial vector with improved attenuation and delivery
      characteristics. The resulting strains exhibited enhanced gene and protein
      release and inducible cellular death. In addition, the new vectors demonstrated
      improved gene delivery and cytotoxicity profiles to RAW264.7 macrophage APCs. 

PMID- 25849746
TI  - Pd(II)-Catalyzed Pyridine N-Oxides Directed Arylation of Unactivated Csp(3)-H
      Bonds.
AB  - A novel Pd(II)-catalyzed pyridine N-oxide directed remote arylation of
      unactivated Csp(3)-H bonds in aliphatic amides with aryl iodides has been
      developed. This protocol allows installing various aryl groups at the beta- or
      gamma-Csp(3) atom of alkyl carboxylic acid amides. The key palladabicyclic
      intermediate of this transformation has been identified by HR-MS and (1)H NMR
      method. 

PMID- 25849745
TI  - Inhibition of iNOS as a novel effective targeted therapy against triple-negative
      breast cancer.
AB  - INTRODUCTION: Triple-negative breast cancer (TNBC) is an aggressive form of
      breast cancer with no effective targeted therapy. Inducible nitric oxide synthase
      (iNOS) is associated with poor survival in patients with breast cancer by
      increasing tumor aggressiveness. This work aimed to investigate the potential of
      iNOS inhibitors as a targeted therapy for TNBC. We hypothesized that inhibition
      of endogenous iNOS would decrease TNBC aggressiveness by reducing tumor
      initiation and metastasis through modulation of epithelial-mesenchymal transition
      (EMT)-inducing factors. METHODS: iNOS protein levels were determined in 83 human
      TNBC tissues and correlated with clinical outcome. Proliferation, mammosphere
      forming efficiency, migration, and EMT transcription factors were assessed in
      vitro after iNOS inhibition. Endogenous iNOS targeting was evaluated as a
      potential therapy in TNBC mouse models. RESULTS: High endogenous iNOS expression
      was associated with worse prognosis in patients with TNBC by gene expression as
      well as immunohistochemical analysis. Selective iNOS (1400 W) and pan-NOS (L-NMMA
      and L-NAME) inhibitors diminished cell proliferation, cancer stem cell self
      renewal, and cell migration in vitro, together with inhibition of EMT
      transcription factors (Snail, Slug, Twist1, and Zeb1). Impairment of hypoxia
      inducible factor 1alpha, endoplasmic reticulum stress (IRE1alpha/XBP1), and the
      crosstalk between activating transcription factor 3/activating transcription
      factor 4 and transforming growth factor beta was observed. iNOS inhibition
      significantly reduced tumor growth, the number of lung metastases, tumor
      initiation, and self-renewal. CONCLUSIONS: Considering the effectiveness of L
      NMMA in decreasing tumor growth and enhancing survival rate in TNBC, we propose a
      targeted therapeutic clinical trial by re-purposing the pan-NOS inhibitor L-NMMA,
      which has been extensively investigated for cardiogenic shock as an anti-cancer
      therapeutic.

PMID- 25849748
TI  - The quantum theory of rural practice.

PMID- 25849747
TI  - Consumption of Red/Processed Meat and Colorectal Carcinoma: Possible Mechanisms
      Underlying the Significant Association.
AB  - Epidemiology and experimental studies provide an overwhelming support of the
      notion that diets high in red or processed meat accompany an elevated risk of
      developing pre-neoplastic colorectal adenoma and frank colorectal carcinoma
      (CRC). The underlying mechanisms are disputed; thus several hypotheses have been
      proposed. A large body of reports converges, however, on haem and nitrosyl haem
      as major contributors to the CRC development, presumably acting through various
      mechanisms. Apart from a potentially higher intestinal mutagenic load among
      consumers on a diet rich in red/processed meat, other mechanisms involving subtle
      interference with colorectal stem/progenitor cell survival or maturation are
      likewise at play. From an overarching perspective, suggested candidate mechanisms
      for red/processed meat-induced CRC appear as three partly overlapping tenets: (i)
      increased N-nitrosation/oxidative load leading to DNA adducts and lipid
      peroxidation in the intestinal epithelium, (ii) proliferative stimulation of the
      epithelium through haem or food-derived metabolites that either act directly or
      subsequent to conversion, and (iii) higher inflammatory response, which may
      trigger a wide cascade of pro-malignant processes. In this review, we summarize
      and discuss major findings of the area in the context of potentially pertinent
      mechanisms underlying the above-mentioned association between consumption of
      red/processed meat and increased risk of developing CRC. 

PMID- 25849750
TI  - President's message. Enhanced surgical services.

PMID- 25849752
TI  - Nurse-led diabetes management in remote locations.
AB  - INTRODUCTION: Nurse-led diabetes management has been shown to be effective in
      urban and regional general practice. We sought to test the feasibility of
      providing a nurse-led annual cycle of diabetes care in a remote location and to
      explore the factors that patients indicated were important in diabetes self
      management. METHODS: We conducted a pilot study in 3 locations: 1 town and 2
      small townships in remote Australia. A chronic disease nurse (CDN) visited each
      patient over the course of a year. We examined patient clinical outcomes and
      interview data. We estimated the cost per hour of the CDN's time, including
      travel time, per 1% drop in glycated hemoglobin (HbA1C). RESULTS: A total of 21
      patients participated in the pilot study. Clinical findings showed significant
      reductions in HbA1C levels after the nurse-led intervention. Patients reported
      that they trusted the nurse and thought her advice was pitched at their level.
      Patients were motivated through a process that included emotional response,
      change identity and acceptance. The estimated cost in CDN hours per 1% drop in
      HbA1C level was A$242.95 (Can$237.60). CONCLUSION: Nurse-led diabetes care
      motivated patients to manage their diabetes and resulted in a significant
      improvement in diabetes management in this remote setting.

PMID- 25849753
TI  - Vancomycin use in a rural hospital: a 3-year retrospective study.
AB  - INTRODUCTION: Urban centres often perform audits of vancomycin use as they face
      outbreaks of resistant organisms. We undertook this study to understand the
      indications and duration of intravenous vancomycin in a rural setting. METHODS:
      We conducted a retrospective chart audit for all patients who received
      intravenous vancomycin over a 3-year period at a rural hospital in northwestern
      Ontario. RESULTS: Vancomycin was used intravenously in 180 patients during the
      study period. It was used for short courses (median 3 d), and serum levels were
      below target 72% of the time. CONCLUSION: High rates of invasive methicillin
      resistant Staphylococcus aureus bacteremia and limited antibiotic choices in the
      field likely contributed to short courses of this antibiotic. Further study on
      clinical severity and antibiotic choice is needed. Additionally, weight-based
      dosing may result in target serum levels being achieved more frequently.

PMID- 25849754
TI  - Country cardiograms case 53.

PMID- 25849755
TI  - The occasional posterior hip dislocation reduction.

PMID- 25849757
TI  - From the T-dot to the Rock: my journey in rural family medicine.

PMID- 25849758
TI  - Biology, ecology and distribution of the tick, Haemaphysalis longicornis Neumann
      (Acari: Ixodidae) in New Zealand.
AB  - Haemaphysalis longicornis is the only tick in New Zealand that infests livestock.
      Throughout its range H. longicornis is exposed to and exhibits tolerance to a
      wide range of environmental conditions, although it flourishes more in moist,
      warm-temperate environments. This review examines aspects of the biology,
      physiology and ecology of H. longicornis that determine its distribution and
      seasonal activity in New Zealand, based on laboratory and field studies. Examples
      are also drawn from studies outside New Zealand for comparative purposes,
      especially in the context of seasonal activity as seen in less temperate
      latitudes. The tick is able to withstand a wide range of temperature, from its
      developmental threshold of ~12 degrees C to nearly 40 degrees C at its lethal
      limit, but its tolerance of dehydration is less wide, especially in the larva and
      adult, the former especially being the stage that largely determines suitable
      biotopes for the tick and its present distributional limits. The importance of H.
      longicornis to the New Zealand livestock industry has recently increased through
      the establishment and spread of Theileria orientalis Ikeda among dairy and beef
      cattle, although the tick has always posed production-limiting problems for
      cattle, deer and to a lesser extent, sheep. The tick's role as a vector of
      theileriosis and how aspects of the tick's biology affect the spread and
      maintenance of this disease are discussed. It is proposed that, of available
      wildlife hosts, the brown hare with its wide-ranging habits, is an important
      disseminator of ticks. Currently control of ticks is difficult partly because of
      their wide host range, overlapping activity periods of stadia, and also because
      the greater part of their annual cycle is spent on pasture. This means that
      acaricides alone do not satisfactorily reduce tick populations or provide
      comprehensive protection to stock, so integrated management combining pasture
      management with good husbandry and chemical prophylaxis is advocated. 

PMID- 25849759
TI  - Fixational saccades during grating detection and discrimination.
AB  - We investigated the patterns of fixational saccades in human observers performing
      two classical perceptual tasks: grating detection and discrimination. First,
      participants were asked to detect a vertical or tilted grating with one of three
      spatial frequencies and one of four luminance contrast levels. In the second
      experiment, participants had to discriminate the spatial frequency of two supra
      threshold gratings. The gratings were always embedded in additive, high- or low
      contrast pink noise. We observed that the patterns of fixational saccades were
      highly idiosyncratic among participants. Moreover, during the grating detection
      task, the amplitude and the number of saccades were inversely correlated with
      stimulus visibility. We did not find a systematic relationship between saccade
      parameters and grating frequency, apart from a slight decrease of saccade
      amplitude during grating discrimination with higher spatial frequencies. No
      consistent changes in the number and amplitude of fixational saccades with
      performance accuracy were reported. Surprisingly, during grating detection,
      saccade number and amplitude were similar in grating-with-noise and noise-only
      displays. Grating orientation did not affect substantially saccade direction in
      either task. The results challenge the idea that, when analyzing low-level
      spatial properties of visual stimuli, fixational saccades can be adapted in order
      to extract task-relevant information optimally. Rather, saccadic patterns seem to
      be overall modulated by task context, stimulus visibility and individual
      variability. 

PMID- 25849760
TI  - Theoretical investigation on the restoring step of the carbonic anhydrase
      catalytic cycle for natural and promiscuous substrates.
AB  - In the present study steered molecular dynamics simulations were applied to
      investigate the unbinding process of the complex of human carbonic anhydrase with
      the natural HCO3(-) and promiscuous H2NCOHN(-) products. This process is crucial
      for restoring the catalytic cycle of the enzyme. This investigation set out to
      give further insights on the release mechanism involved in the case of the
      promiscuous product believed suicide inhibitor for the hCAII against the natural
      final product. In particular, on the basis of the NPT molecular dynamics
      simulations performed on the bicarbonate, the penta-coordinated complex with the
      water is observed, while in the case of the ureate the same event does not take
      place. At this purpose the calculated potential of mean force based on the
      steered molecular dynamics (SMD) simulations shed light on an optimal pathway for
      the releasing of the products. 

PMID- 25849761
TI  - Functional characterization of CYP107W1 from Streptomyces avermitilis and
      biosynthesis of macrolide oligomycin A.
AB  - Streptomyces avermitilis contains 33 cytochrome P450 genes in its genome, many of
      which play important roles in the biosynthesis process of antimicrobial agents.
      Here, we characterized the biochemical function and structure of CYP107W1 from S.
      avermitilis, which is responsible for the 12-hydroxylation reaction of oligomycin
      C. CYP107W1 was expressed and purified from Escherichia coli. Purified proteins
      exhibited the typical CO-binding spectrum of P450. Interaction of oligomycin C
      and oligomycin A (12-hydroxylated oligomycin C) with purified CYP107W1 resulted
      in a type I binding with Kd values of 14.4 +/- 0.7 MUM and 2.0 +/- 0.1 MUM,
      respectively. LC-mass spectrometry analysis showed that CYP107W1 produced
      oligomycin A by regioselectively hydroxylating C12 of oligomycin C. Steady-state
      kinetic analysis yielded a kcat value of 0.2 min(-1) and a Km value of 18 MUM.
      The crystal structure of CYP107W1 was determined at 2.1 A resolution. The overall
      P450 folding conformations are well conserved, and the open access binding pocket
      for the large macrolide oligomycin C was observed above the distal side of heme.
      This study of CYP107W1 can help a better understanding of clinically important
      P450 enzymes as well as their optimization and engineering for synthesizing novel
      antibacterial agents and other pharmaceutically important compounds.

PMID- 25849763
TI  - Amilorides bind to the quinone binding pocket of bovine mitochondrial complex I.
AB  - Amilorides, well-known inhibitors of Na(+)/H(+) antiporters, were previously
      shown to inhibit bacterial and mitochondrial NADH-quinone oxidoreductase (complex
      I) but were markedly less active for complex I. Because membrane subunits ND2,
      ND4, and ND5 of bovine complex I are homologous to Na(+)/H(+) antiporters,
      amilorides have been thought to bind to any or all of the antiporter-like
      subunits; however, there is currently no direct experimental evidence that
      supports this notion. To identify the binding site of amilorides in bovine
      complex I, we synthesized two photoreactive amilorides (PRA1 and PRA2), which
      have a photoreactive azido (-N3) group and terminal alkyne (-C=CH) group at the
      opposite ends of the molecules, respectively, and conducted photoaffinity
      labeling with bovine heart submitochondrial particles. The terminal alkyne group
      allows various molecular tags to covalently attach to it via Cu(+)-catalyzed
      click chemistry, thereby allowing purification and/or detection of the labeled
      peptides. Proteomic analyses revealed that PRA1 and PRA2 label none of the
      antiporter-like subunits; they specifically label the accessory subunit B14.5a
      and core subunit 49 kDa (N-terminal region of Thr25-Glu115), respectively.
      Suppressive effects of ordinary inhibitors (bullatacin, fenpyroximate, and
      quinazoline), which bind to the putative quinone binding pocket, on labeling were
      fairly different between the B14.5a and 49 kDa subunits probably because the
      binding positions of the three inhibitors differ within the pocket. The results
      of this study clearly demonstrate that amilorides inhibit complex I activity by
      occupying the quinone binding pocket rather than directly blocking translocation
      of protons through the antiporter-like subunits (ND2, ND4, and ND5). The
      accessory subunit B14.5a may be located adjacent to the N-terminal region of the
      49 kDa subunits. The structural features of the quinone binding pocket in bovine
      complex I were discussed on the basis of these results.

PMID- 25849762
TI  - Structure-Based Design of Potent and Selective Inhibitors of the Metabolic Kinase
      PFKFB3.
AB  - A weak screening hit with suboptimal physicochemical properties was optimized
      against PFKFB3 kinase using critical structure-guided insights. The resulting
      compounds demonstrated high selectivity over related PFKFB isoforms and
      modulation of the target in a cellular context. A selected example demonstrated
      exposure in animals following oral dosing. Examples from this series may serve as
      useful probes to understand the emerging biology of this metabolic target. 

PMID- 25849765
TI  - Absence of effects on the rat sperm quality after subacute exposure to low doses
      of fungicide prochloraz.
AB  - Prochloraz (PCZ) is a fungicide and androgen-receptor antagonist used worldwide
      in horticulture and agriculture. Pre- and perinatal exposure to this pesticide
      during sexual differentiation is deleterious for male offspring. Since data on
      the effects of PCZ on epididymal functions are scarce, and because sperm
      maturation occurs in this organ, the present investigation aimed to determine
      whether low PCZ doses administered to rats during the phase of sperm transit
      through the epididymis might affect the morphophysiology of this organ and sperm
      quality. Adult male Wistar rats were assigned to 4 different groups: 0 (control,
      vehicle) or 10, 15, or 30 mg/kg bw/d PCZ diluted in corn oil administered orally
      for 4 consecutive days. Morphofunctional parameters of the male reproductive
      tract, hormone concentrations, sperm evaluations, and fertility and
      histopathologic analysis of testis and epididymis were assessed. There were no
      statistically significant differences between treated and control groups in
      relation to all evaluated parameters. Data demonstrated show that PCZ exposure
      for a brief 4-d exposure and low doses did not produce reproductive toxicity or
      compromise sperm quality in adult rats. 

PMID- 25849764
TI  - AtEAF1 is a potential platform protein for Arabidopsis NuA4 acetyltransferase
      complex.
AB  - BACKGROUND: Histone acetyltransferase complex NuA4 and histone variant exchanging
      complex SWR1 are two chromatin modifying complexes which act cooperatively in
      yeast and share some intriguing structural similarities. Protein subunits of NuA4
      and SWR1-C are highly conserved across eukaryotes, but form different
      multiprotein arrangements. For example, the human TIP60-p400 complex consists of
      homologues of both yeast NuA4 and SWR1-C subunits, combining subunits necessary
      for histone acetylation and histone variant exchange. It is currently not known
      what protein complexes are formed by the plant homologues of NuA4 and SWR1-C
      subunits. RESULTS: We report on the identification and molecular characterization
      of AtEAF1, a new subunit of Arabidopsis NuA4 complex which shows many
      similarities to the platform protein of the yeast NuA4 complex. AtEAF1 copurifies
      with Arabidopsis homologues of NuA4 and SWR1-C subunits ARP4 and SWC4 and
      interacts physically with AtYAF9A and AtYAF9B, homologues of the YAF9 subunit.
      Plants carrying a T-DNA insertion in one of the genes encoding AtEAF1 showed
      decreased FLC expression and early flowering, similarly to Atyaf9 mutants.
      Chromatin immunoprecipitation analyses of the single mutant Ateaf1b-2 and
      artificial miRNA knock-down Ateaf1 lines showed decreased levels of H4K5
      acetylation in the promoter regions of major flowering regulator genes, further
      supporting the role of AtEAF1 as a subunit of the plant NuA4 complex.
      CONCLUSIONS: Growing evidence suggests that the molecular functions of the NuA4
      and SWR1 complexes are conserved in plants and contribute significantly to plant
      development and physiology. Our work provides evidence for the existence of a
      yeast-like EAF1 platform protein in A. thaliana, filling an important gap in the
      knowledge about the subunit organization of the plant NuA4 complex.

PMID- 25849766
TI  - Benzophenone-1 and nonylphenol stimulated MCF-7 breast cancer growth by
      regulating cell cycle and metastasis-related genes via an estrogen receptor alpha
      dependent pathway.
AB  - Endocrine-disrupting chemicals (EDC) are defined as environmental compounds that
      produce adverse health manifestations in mammals by disrupting the endocrine
      system. Benzophenone-1 (2,4-dihydroxybenzophenone, BP1) and nonylphenol (NP),
      which are discharged from numerous industrial products, are known EDC. The aim of
      this study was to examine the effects of BP1 and NP on proliferation and
      metastasis of MCF-7 human breast cancer cells expressing estrogen receptors (ER).
      Treatment with BP1 (10-5-10-7 M) and NP (10-6-10-7 M) promoted proliferation of
      MCF-7 cells similar to the positive control 17 -beta-estradiol (E2). When ICI
      182,780, an ER antagonist, was co-incubated with E2, BP1, or NP, proliferation of
      MCF-7 cells returned to the level of a control. Addition of BP1 or NP markedly
      induced migration of MCF-7 cells similar to E2. To elucidate the underlying
      molecular mechanisms produced by these EDC, alterations in transcriptional and
      translational levels of proliferation and metastasis-related markers, including
      cyclin D1, p21, and cathepsin D, were determined. Data showed increase in
      expression of cyclin D1 and cathepsin D and decrease in p21 at both
      transcriptional and translational levels. However, BP1- or NP-induced alterations
      of these genes were blocked by ICI 182,780, suggesting that changes in expression
      of these genes may be regulated by an ERalpha-dependent pathway. In conclusion,
      BP1 and NP may accelerate growth of MCF-7 breast cancer cells by regulating cell
      cycle-related genes and promote cancer metastasis through amplification of
      cathepsin D.

PMID- 25849767
TI  - Fine particulate air pollution and outpatient department visits for headache in
      Taipei, Taiwan.
AB  - This study was undertaken to determine whether there was an association between
      fine particle matter (PM(2.5)) levels and daily outpatient department visits
      (OPD) for headaches in Taipei, Taiwan. Daily OPD visits for headaches and ambient
      air pollution data for Taipei were obtained for the period 2006-2011. The
      relative risk of visits for OPD headaches 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 OPD visits for headaches were significantly
      associated with levels of PM(2.5) both on warm days (>23 degrees C) and cool days
      (<23 degrees C), with an interquartile range rise associated with a 12% (95% CI =
      10-14%) and 3% (95% CI = 1-5%) elevation in OPD visits for headaches,
      respectively. In the two-pollutant models, PM(2.5) remained significant after
      inclusion of sulfur dioxide (SO2) or ozone (O3) on both warm and cool days. This
      study provides evidence that higher levels of PM(2.5) increase the risk of OPD
      visits for headaches in Taipei, Taiwan.

PMID- 25849768
TI  - Altered expression levels of neurodevelopmental proteins in fetal brains of BTBR
      T+tf/J mice with autism-like behavioral characteristics.
AB  - Autism is a brain developmental disorder with characteristics of social
      interaction defects, language and communication dysfunction, and repetitive
      behavior. Occurrence of autism is continuously increasing, but the cause of
      autism is not clearly defined. Genetic linkage or environmental factors were
      proposed as sources for pathogenesis of autism. BTBR T+tf/J (BTBR) mice were
      reported as an appropriate animal model for autism investigation because of their
      similarities in behavioral abnormalities with human autistic subjects. The aim of
      this study was to evaluate expression levels of proteins involved with brain
      development at fetal stage of BTBR mice. FVB/NJ mice were used as a control
      strain because of their social behaviors. Level of fetal brain immunoglobulin
      (Ig) G deposit was also evaluated. Fetal brains were obtained at d 18 of
      gestational period. Thirty-one and 27 fetuses were obtained from 3 pregnant BTBR
      and FVB dams, respectively. The level of glial fibrillary acidic protein
      expression was significantly lower in fetal brains of BTBR than FVB/NJ mice.
      Expression of brain-derived neurotrophic factor and myelin basic protein was
      significantly more upregulated in BTBR than in FVB/NJ mice. No significant
      difference was obtained for nerve growth factor between the two strains. Levels
      of IgG isotypes deposited in fetal brain of BTBR mice were significantly higher
      than in FVB mice except for IgG1. Overall, these results suggest that prenatal
      alterations in expression of various fetal brain proteins may be implicated in
      aberrant behavioral characteristics of BTBR mice. 

PMID- 25849769
TI  - The air quality health index and emergency department visits for urticaria in
      Windsor, Canada.
AB  - Ambient air pollution exposure has been associated with several health
      conditions, limited not only to respiratory and cardiovascular systems but also
      to cutaneous tissues. However, few epidemiological studies examined pollution
      exposure on skin problems. Basically, the common mechanism by which pollution may
      affect skin physiology is by induction of oxidative stress and inflammation.
      Urticaria is among the skin pathologies that have been associated with pollution.
      Based on the combined effects of three ambient air pollutants, ozone (O3),
      nitrogen dioxide (NO2), and fine particulate matter (PM) with a median
      aerodynamic diameter of less than 2.5 MUm (PM(2.5)), on mortality, the Air
      Quality Health Index (AQHI) in Canada was developed. The aim of this study was to
      examine the associations of short-term changes in AQHI with emergency department
      (ED) visits for urticaria in Windsor-area hospitals in Canada. Diagnosed ED
      visits were retrieved from the National Ambulatory Care Reporting System (NACRS).
      A time-stratified case-crossover design was applied to 2905 ED visits (males =
      1215; females = 1690) for urticaria from April 2004 through December 2010. Odds
      ratios (OR) and their corresponding 95% confidence intervals (95%CI) for ED
      visits associated with increase by one unit of risk index were calculated
      employing conditional logistic regression. Positive and significant results were
      observed between AQHI levels and OR for ED visits for urticaria in Windsor for
      lags 2 and 3 days. A distributed lag nonlinear model technique was applied to
      daily counts of ED visits for lags 0 to 10 and significant results were obtained
      from lag 2 to lag 5 and for lag 9. These findings demonstrated associations
      between ambient air pollution and urticarial confirming that air pollution
      affects skin conditions.

PMID- 25849770
TI  - Hematological and hepatic alterations in Brazilian population heavily exposed to
      organochlorine pesticides.
AB  - The aim of this study was to investigate the frequency of hematological and
      hepatic alterations and possible association with serum levels of beta
      hexachlorocyclohexane (beta-HCH), p,p'-DDE, and hexachlorobenzene (HCB) among
      residents in an area heavily contaminated with organochlorine (OC) pesticides. A
      cross-sectional study was conducted in 415 male and 432 female residents aged >14
      years. Serum samples were collected and analyzed for OC pesticides concentrations
      and biochemical parameters. Frequencies of hematological and hepatic alterations
      were calculated for each gender. Association between beta-HCH, p,p'-DDE (1,1
      dichloro-2,2-bis(p-chlorophenyl) ethylene), and HCB levels and presence of
      alterations was determined by logistic regression stratified by gender and
      controlling for confounders. Highest frequencies were observed for eosinophilia
      (23% men and 18% women), low hemoglobin (12% men and 15% women), and low
      erythrocyte count (12% men). High levels of bilirubin, glutamic-oxaloacetic
      transaminase (GOT), and glutamic-pyruvic transaminase (GPT) were observed,
      respectively, in 10, 11, and 12% of men and <10% of women. Gamma-glutamyl
      transferase (GGT) was elevated in 26 and 25% of males and females, respectively.
      Multivariate analysis revealed associations between eosinophilia and beta-HCH in
      men (OR = 1.06, 95%CI = 1.01-1.12) and women (OR = 1.05, 96%CI = 0.99-1.11), p,p'
      DDE in men (OR = 1.03, 95%CI = 0.99-1.06) and women (OR = 1.02, 95%CI = 0.99
      1.06), and HCB in women (OR = 1.54, 95%IC = 0.85-4.45). Beta-HCH was found to be
      associated with increased risk of elevated bilirubin in females (OR = 1.18, 95%CI
      = 1.07-1.29) and males (OR = 4.21, 95%CI = 1.87-9.47 for fourth vs. first
      quintile). Thus, OC pesticides may exert adverse effects on hematopoietic tissue
      and liver in populations chronically exposed to high levels of these compounds. 

PMID- 25849772
TI  - The implications of probability matching for clinician response to vital sign
      alarms: a theoretical study of alarm fatigue.
AB  - Alarm fatigue has been recognised as a significant health technology safety risk.
      'Probability matching', in which clinicians respond to the alarm at a rate
      identical to the perceived reliability of the alarm, has been postulated as a
      model to explain alarm fatigue. In this article, we quantitatively explore the
      implications of probability matching for systolic blood pressure alarms. We find
      that probability matching could have a profound effect on clinician response to
      the alarm, with a response rate of only 8.6% when the alarm threshold is 90 mm Hg
      and the optimal threshold for a systolic blood pressure alarm would only be 77 mm
      Hg. We use the mathematical framework to assess a mitigation strategy when
      clinicians have a limit to the capacity to respond. We find that a tiered alarm
      in which clinicians receive information on the severity of vital sign
      perturbation significantly improves the opportunity to rescue patients.
      Practitioner Summary: Using a theoretical model, we predict that probability
      matching, a postulated model of clinician behaviour, can result in a profound
      decrease in clinician response to alarms for decreased blood pressure. A
      mitigating strategy is to create alarms that convey information on the degree of
      vital sign perturbation. 

PMID- 25849771
TI  - DNA methylation and transcriptomic changes in response to different lights and
      stresses in 7B-1 male-sterile tomato.
AB  - We reported earlier that 7B-1 mutant in tomato (Solanum lycopersicum L., cv.
      Rutgers), an ABA overproducer, is defective in blue light (B) signaling leading
      to B-specific resistance to abiotic and biotic stresses. Using a methylation
      sensitive amplified polymorphism (MSAP) assay, a number of genes were identified,
      which were differentially methylated between 7B-1 and its wild type (WT)
      seedlings in white (W), blue (B), red (R) lights and dark (D) or in response to
      exogenous ABA and mannitol-induced stresses. The genomic methylation level was
      almost similar in different lights between 7B-1 and WT seedlings, while
      significant differences were observed in response to stresses in D, but not B.
      Using a cDNA-AFLP assay, several transcripts were identified, which were
      differentially regulated between 7B-1 and WT by B or D or in response to
      stresses. Blue light receptors cryptochrome 1 and 2 (CRY1 and CRY2) and
      phototropin 1 and 2 (PHOT1 and PHOT2) were not affected by the 7B-1 mutation at
      the transcriptional level, instead the mutation had likely affected downstream
      components of the light signaling pathway. 5-azacytidine (5-azaC) induced DNA
      hypomethylation, inhibited stem elongation and differentially regulated the
      expression of a number of genes in 7B-1. In addition, it was shown that mir167
      and mir390 were tightly linked to auxin signaling pathway in 5-azaC-treated 7B-1
      seedlings via the regulation of auxin-response factor (ARF) transcripts. Our data
      showed that DNA methylation remodeling is an active epigenetic response to
      different lights and stresses in 7B-1 and WT, and highlighted the differences in
      epigenetic and transcriptional regulation of light and stress responses between
      7B-1 and WT. Furthermore, it shed lights on the crosstalk between DNA
      hypomethylation and miRNA regulation of ARFs expression. This information could
      also be used as a benchmark for future studies of male-sterility in other crops. 

PMID- 25849774
TI  - Niche-induced cell death and epithelial phagocytosis regulate hair follicle stem
      cell pool.
AB  - Tissue homeostasis is achieved through a balance of cell production (growth) and
      elimination (regression). In contrast to tissue growth, the cells and molecular
      signals required for tissue regression remain unknown. To investigate
      physiological tissue regression, we use the mouse hair follicle, which cycles
      stereotypically between phases of growth and regression while maintaining a pool
      of stem cells to perpetuate tissue regeneration. Here we show by intravital
      microscopy in live mice that the regression phase eliminates the majority of the
      epithelial cells by two distinct mechanisms: terminal differentiation of
      suprabasal cells and a spatial gradient of apoptosis of basal cells. Furthermore,
      we demonstrate that basal epithelial cells collectively act as phagocytes to
      clear dying epithelial neighbours. Through cellular and genetic ablation we show
      that epithelial cell death is extrinsically induced through transforming growth
      factor (TGF)-beta activation and mesenchymal crosstalk. Strikingly, our data show
      that regression acts to reduce the stem cell pool, as inhibition of regression
      results in excess basal epithelial cells with regenerative abilities. This study
      identifies the cellular behaviours and molecular mechanisms of regression that
      counterbalance growth to maintain tissue homeostasis. 

PMID- 25849773
TI  - eIF3 targets cell-proliferation messenger RNAs for translational activation or
      repression.
AB  - Regulation of protein synthesis is fundamental for all aspects of eukaryotic
      biology by controlling development, homeostasis and stress responses. The 13
      subunit, 800-kilodalton eukaryotic initiation factor 3 (eIF3) organizes
      initiation factor and ribosome interactions required for productive translation.
      However, current understanding of eIF3 function does not explain genetic evidence
      correlating eIF3 deregulation with tissue-specific cancers and developmental
      defects. Here we report the genome-wide discovery of human transcripts that
      interact with eIF3 using photoactivatable ribonucleoside-enhanced crosslinking
      and immunoprecipitation (PAR-CLIP). eIF3 binds to a highly specific program of
      messenger RNAs involved in cell growth control processes, including cell cycling,
      differentiation and apoptosis, via the mRNA 5' untranslated region. Surprisingly,
      functional analysis of the interaction between eIF3 and two mRNAs encoding the
      cell proliferation regulators c-JUN and BTG1 reveals that eIF3 uses different
      modes of RNA stem-loop binding to exert either translational activation or
      repression. Our findings illuminate a new role for eIF3 in governing a
      specialized repertoire of gene expression and suggest that binding of eIF3 to
      specific mRNAs could be targeted to control carcinogenesis. 

PMID- 25849775
TI  - Structural basis for Na(+) transport mechanism by a light-driven Na(+) pump.
AB  - Krokinobacter eikastus rhodopsin 2 (KR2) is the first light-driven Na(+) pump
      discovered, and is viewed as a potential next-generation optogenetics tool. Since
      the positively charged Schiff base proton, located within the ion-conducting
      pathway of all light-driven ion pumps, was thought to prohibit the transport of a
      non-proton cation, the discovery of KR2 raised the question of how it achieves
      Na(+) transport. Here we present crystal structures of KR2 under neutral and
      acidic conditions, which represent the resting and M-like intermediate states,
      respectively. Structural and spectroscopic analyses revealed the gating
      mechanism, whereby the flipping of Asp116 sequesters the Schiff base proton from
      the conducting pathway to facilitate Na(+) transport. Together with the structure
      based engineering of the first light-driven K(+) pumps, electrophysiological
      assays in mammalian neurons and behavioural assays in a nematode, our studies
      reveal the molecular basis for light-driven non-proton cation pumps and thus
      provide a framework that may advance the development of next-generation
      optogenetics. 

PMID- 25849777
TI  - An ultrafast rechargeable aluminium-ion battery.
AB  - The development of new rechargeable battery systems could fuel various energy
      applications, from personal electronics to grid storage. Rechargeable aluminium
      based batteries offer the possibilities of low cost and low flammability,
      together with three-electron-redox properties leading to high capacity. However,
      research efforts over the past 30 years have encountered numerous problems, such
      as cathode material disintegration, low cell discharge voltage (about 0.55 volts;
      ref. 5), capacitive behaviour without discharge voltage plateaus (1.1-0.2 volts
      or 1.8-0.8 volts) and insufficient cycle life (less than 100 cycles) with rapid
      capacity decay (by 26-85 per cent over 100 cycles). Here we present a
      rechargeable aluminium battery with high-rate capability that uses an aluminium
      metal anode and a three-dimensional graphitic-foam cathode. The battery operates
      through the electrochemical deposition and dissolution of aluminium at the anode,
      and intercalation/de-intercalation of chloroaluminate anions in the graphite,
      using a non-flammable ionic liquid electrolyte. The cell exhibits well-defined
      discharge voltage plateaus near 2 volts, a specific capacity of about 70 mA h g(
      1) and a Coulombic efficiency of approximately 98 per cent. The cathode was found
      to enable fast anion diffusion and intercalation, affording charging times of
      around one minute with a current density of ~4,000 mA g(-1) (equivalent to ~3,000
      W kg(-1)), and to withstand more than 7,500 cycles without capacity decay. 

PMID- 25849776
TI  - Diverse coupling of neurons to populations in sensory cortex.
AB  - A large population of neurons can, in principle, produce an astronomical number
      of distinct firing patterns. In cortex, however, these patterns lie in a space of
      lower dimension, as if individual neurons were "obedient members of a huge
      orchestra". Here we use recordings from the visual cortex of mouse (Mus musculus)
      and monkey (Macaca mulatta) to investigate the relationship between individual
      neurons and the population, and to establish the underlying circuit mechanisms.
      We show that neighbouring neurons can differ in their coupling to the overall
      firing of the population, ranging from strongly coupled 'choristers' to weakly
      coupled 'soloists'. Population coupling is largely independent of sensory
      preferences, and it is a fixed cellular attribute, invariant to stimulus
      conditions. Neurons with high population coupling are more strongly affected by
      non-sensory behavioural variables such as motor intention. Population coupling
      reflects a causal relationship, predicting the response of a neuron to
      optogenetically driven increases in local activity. Moreover, population coupling
      indicates synaptic connectivity; the population coupling of a neuron, measured in
      vivo, predicted subsequent in vitro estimates of the number of synapses received
      from its neighbours. Finally, population coupling provides a compact summary of
      population activity; knowledge of the population couplings of n neurons predicts
      a substantial portion of their n(2) pairwise correlations. Population coupling
      therefore represents a novel, simple measure that characterizes the relationship
      of each neuron to a larger population, explaining seemingly complex network
      firing patterns in terms of basic circuit variables. 

PMID- 25849779
TI  - Correction: association between physical activity knowledge and levels of
      physical activity in Chinese adults with type 2 diabetes.

PMID- 25849780
TI  - Iron oxide nanorods as high-performance magnetic resonance imaging contrast
      agents.
AB  - An efficient magnetic resonance imaging (MRI) contrast agent with a high R2
      relaxivity value is achieved by controlling the shape of iron oxide to rod like
      morphology with a length of 30-70 nm and diameter of 4-12 nm. Fe3O4 nanorods of
      70 nm length, encapsulated with polyethyleneimine show a very high R2 relaxivity
      value of 608 mM(-1) s(-1). The enhanced MRI contrast of nanorods is attributed to
      their higher surface area and anisotropic morphology. The higher surface area
      induces a stronger magnetic field perturbation over a larger volume more
      effectively for the outer sphere protons. The shape anisotropy contribution is
      understood by calculating the local magnetic field of nanorods and spherical
      nanoparticles under an applied magnetic field (3 Tesla). As compared to spherical
      geometry, the induced magnetic field of a rod is stronger and hence the stronger
      magnetic field over a large volume leads to a higher R2 relaxivity of nanorods. 

PMID- 25849778
TI  - Predictive value of S100-B and copeptin for outcomes following seizure: the
      BISTRO International Cohort Study.
AB  - OBJECTIVE: To evaluate the performance of S100-B protein and copeptin, in
      addition to clinical variables, in predicting outcomes of patients attending the
      emergency department (ED) following a seizure. METHODS: We prospectively included
      adult patients presented with an acute seizure, in four EDs in France and the
      United Kingdom. Participants were followed up for 28 days. The primary endpoint
      was a composite of seizure recurrence, all-cause mortality, hospitalization or
      rehospitalisation, or return visit in the ED within seven days. RESULTS: Among
      the 389 participants included in the analysis, 156 (40%) experienced the primary
      endpoint within seven days and 195 (54%) at 28 days. Mean levels of both S100-B
      (0.11 MUg/l [95% CI 0.07-0.20] vs 0.09 MUg/l [0.07-0.14]) and copeptin (23 pmol/l
      [9-104] vs 17 pmol/l [8-43]) were higher in participants meeting the primary
      endpoint. However, both biomarkers were poorly predictive of the primary outcome
      with a respective area under the receiving operator characteristic curve of 0.57
      [0.51-0.64] and 0.59 [0.54-0.64]. Multivariable logistic regression analysis
      identified higher age (odds ratio [OR] 1.3 per decade [1.1-1.5]), provoked
      seizure (OR 4.93 [2.5-9.8]), complex partial seizure (OR 4.09 [1.8-9.1]) and
      first seizure (OR 1.83 [1.1-3.0]) as independent predictors of the primary
      outcome. A second regression analysis including the biomarkers showed no
      additional predictive benefit (S100-B OR 3.89 [0.80-18.9] copeptin OR 1 [1.00
      1.00]). CONCLUSION: The plasma biomarkers S100-B and copeptin did not improve
      prediction of poor outcome following seizure. Higher age, a first seizure, a
      provoked seizure and a partial complex seizure are independently associated with
      adverse outcomes.

PMID- 25849781
TI  - Structural, biochemical, and physiological characterization of photosynthesis in
      leaf-derived cup-shaped galls on Litsea acuminata.
AB  - BACKGROUND: The source and sink relationships between insect-induced galls and
      host plant leaves are interesting. In this research, we collected cup-like galls
      induced by Bruggmanniella sp. (Diptera: Cecidomyiidae) on host leaves of Litsea
      acuminata and assessed them to investigate source-sink relationships between
      galls and host leaves. We characterized several of their photosynthetic
      characteristics including chlorophyll fluorescence (Fv/Fm), stomatal conductance,
      and photosynthetic capacity, biochemical components such as total soluble sugar,
      starches, free amino acids, and soluble proteins. The structural analyses were
      performed under confocal, light, and scanning electron microscopies. RESULTS:
      Compared with host leaves, galls exhibited slightly lower chlorophyll
      fluorescence; however, stomatal conductance and photosynthetic capacity were not
      detected at all. Galls accumulated higher total soluble sugars and free amino
      acids but less soluble proteins than host leaves. No stomata was observed on
      exterior or interior gall surfaces under light or scanning electron microscopy,
      but their inner surfaces were covered with fungal hyphae. Confocal imagery showed
      a gradient of chloroplasts distribution between gall outer and inner surfaces.
      CONCLUSIONS: Our results strongly suggest that leaf-derived cecidomyiid galls are
      a type of chlorophyll-deficient non-leaf green tissue and consists on a novel
      sink in L. acuminate.

PMID- 25849782
TI  - Transcriptomic analysis of differentially expressed genes in an orange-pericarp
      mutant and wild type in pummelo (Citrus grandis).
AB  - BACKGROUND: The external colour of fruit is a crucial quality feature, and the
      external coloration of most citrus fruits is due to the accumulation of
      carotenoids. The molecular regulation of carotenoid biosynthesis and accumulation
      in pericarp is limited due to the lack of mutant. In this work, an orange
      pericarp mutant (MT) which showed altered pigmentation in the pericarp was used
      to identify genes potentially related to the regulation of carotenoid
      accumulation in the pericarp. RESULTS: High Performance Liquid Chromatography
      (HPLC) analysis revealed that the pericarp from MT fruits had a 10.5-fold
      increase of beta-carotene content over that of the Wild Type (WT). Quantitative
      real-time PCR (qRT-PCR) analysis showed that the expression of all downstream
      carotenogenic genes was lower in MT than in WT, suggesting that down-regulation
      is critical for the beta-carotene increase in the MT pericarp. RNA-seq analysis
      of the transcriptome revealed extensive changes in the MT gene expression level,
      with 168 genes down-regulated and 135 genes up-regulated. Gene ontology (GO) and
      KEGG pathway analyses indicated seven reliable metabolic pathways are altered in
      the mutant, including carbon metabolism, starch and sucrose metabolism and
      biosynthesis of amino acids. The transcription factors and genes corresponding to
      effected metabolic pathways may involved in the carotenoid regulation was
      confirmed by the qRT-PCR analysis in the MT pericarp. CONCLUSIONS: This study has
      provided a global picture of the gene expression changes in a novel mutant with
      distinct color in the fruit pericarp of pummelo. Interpretation of differentially
      expressed genes (DEGs) revealed new insight into the molecular regulation of beta
      carotene accumulation in the MT pericarp.

PMID- 25849783
TI  - Cardiac structure and function are altered in type 2 diabetes and non-alcoholic
      fatty liver disease and associate with glycemic control.
AB  - BACKGROUND: Both non-alcoholic fatty liver disease (NAFLD) and Type 2 diabetes
      increase the risk of developing cardiovascular disease. The metabolic processes
      underlying NAFLD and Type 2 diabetes are part of an integrated mechanism but
      little is known about how these conditions may differentially affect the heart.
      We compared the impact of NAFLD and Type 2 diabetes on cardiac structure,
      function and metabolism. METHODS: 19 adults with Type 2 diabetes (62 +/- 8
      years), 19 adults with NAFLD (54 +/- 15 years) and 19 healthy controls (56 +/- 14
      years) underwent assessment of cardiac structure, function and metabolism using
      high resolution magnetic resonance imaging, tagging and spectroscopy at 3.0 T.
      RESULTS: Adults with NAFLD and Type 2 diabetes demonstrate concentric remodelling
      with an elevated eccentricity ratio compared to controls (1.05 +/- 0.3 vs. 1.12
      +/- 0.2 vs. 0.89 +/- 0.2 g/ml; p < 0.05). Despite this, only the Type 2 diabetes
      group demonstrate significant systolic and diastolic dysfunction evidenced by a
      reduced stroke index (31 +/- 7vs. controls, 38 +/- 10, p < 0.05 ml/m2) and
      reduced E/A (0.9 +/- 0.4 vs. controls, 1.9 +/- 1.4, p < 0.05) respectively. The
      torsion to shortening ratio was higher in Type 2 diabetes compared to NAFLD (0.58
      +/- 0.16 vs. 0.44 +/- 0.13; p < 0.05). Significant associations were observed
      between fasting blood glucose/HbA1c and diastolic parameters as well as the
      torsion to shortening ratio (all p < 0.05). Phosphocreatine/adenosine
      triphosphate ratio was not altered in NAFLD or Type 2 diabetes compared to
      controls. CONCLUSIONS: Changes in cardiac structure are evident in adults with
      Type 2 diabetes and NAFLD without overt cardiac disease and without changes in
      cardiac energy metabolism. Only the Type 2 diabetes group display diastolic and
      subendocardial dysfunction and glycemic control may be a key mediator of these
      cardiac changes. Therapies should be explored to target these preclinical cardiac
      changes to modify cardiovascular risk associated with Type 2 diabetes and NAFLD.

PMID- 25849784
TI  - Multi drug and other forms of drug resistant tuberculosis are uncommon among
      treatment naive tuberculosis patients in Tanzania.
AB  - BACKGROUND: Surveillance and effective management of drug resistance is important
      to sustaining tuberculosis (TB) control efforts. We aimed to determine resistance
      rates to first line anti tuberculosis drugs and to describe factors associated
      with the resistance to any of the first line anti tuberculosis drugs in Dar es
      Salaam Tanzania. MATERIALS: Newly diagnosed, TB patients with neither history of
      tuberculosis treatment nor isoniazid prophylaxis were included into the study.
      Sputum specimens were cultured on either mycobacteria growth indicator tube 960
      (MGIT 960) or Lowenstein Jenstein (LJ) medium supplemented with either glycerol
      (GLJ) or pyruvate (PLJ). Drug susceptibility for isoniazid, rifampicin,
      streptomycin and ethambutol was determined by either Lowenstein-Jensen (LJ)
      medium or mycobacteria growth indicator tube 960 (MGIT 960). RESULTS: A total of
      933 newly diagnosed TB patients, were included into the study. Multi drug
      resistance (MDR) tuberculosis was detected among 2 (0.2%) patients. Resistance to
      any of the four tested drugs was detected among 54 (5.8%) patients. Mono
      resistance to isoniazid, rifampicin, streptomycin and ethambutol were 21(2.3%), 3
      (0.3%), 13 (1.4%), 9 (1.0%) respectively. CONCLUSION: Primary resistance to first
      line anti tuberculosis drugs is still low in this setting. Continued vigilance
      including periodic national surveillance of anti-tuberculosis resistance is
      recommended.

PMID- 25849785
TI  - Gate-tunable memristive phenomena mediated by grain boundaries in single-layer
      MoS2.
AB  - Continued progress in high-speed computing depends on breakthroughs in both
      materials synthesis and device architectures. The performance of logic and memory
      can be enhanced significantly by introducing a memristor, a two-terminal device
      with internal resistance that depends on the history of the external bias
      voltage. State-of-the-art memristors, based on metal-insulator-metal (MIM)
      structures with insulating oxides, such as TiO2, are limited by a lack of control
      over the filament formation and external control of the switching voltage. Here,
      we report a class of memristors based on grain boundaries (GBs) in single-layer
      MoS2 devices. Specifically, the resistance of GBs emerging from contacts can be
      easily and repeatedly modulated, with switching ratios up to ~10(3) and a dynamic
      negative differential resistance (NDR). Furthermore, the atomically thin nature
      of MoS2 enables tuning of the set voltage by a third gate terminal in a field
      effect geometry, which provides new functionality that is not observed in other
      known memristive devices.

PMID- 25849786
TI  - Nanoscale imaging: Tomography for plasmonics.

PMID- 25849787
TI  - A metal-free bifunctional electrocatalyst for oxygen reduction and oxygen
      evolution reactions.
AB  - The oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) are
      traditionally carried out with noble metals (such as Pt) and metal oxides (such
      as RuO2 and MnO2) as catalysts, respectively. However, these metal-based
      catalysts often suffer from multiple disadvantages, including high cost, low
      selectivity, poor stability and detrimental environmental effects. Here, we
      describe a mesoporous carbon foam co-doped with nitrogen and phosphorus that has
      a large surface area of ~1,663 m(2) g(-1) and good electrocatalytic properties
      for both ORR and OER. This material was fabricated using a scalable, one-step
      process involving the pyrolysis of a polyaniline aerogel synthesized in the
      presence of phytic acid. We then tested the suitability of this N,P-doped carbon
      foam as an air electrode for primary and rechargeable Zn-air batteries. Primary
      batteries demonstrated an open-circuit potential of 1.48 V, a specific capacity
      of 735 mAh gZn(-1) (corresponding to an energy density of 835 Wh kgZn(-1)), a
      peak power density of 55 mW cm(-2), and stable operation for 240 h after
      mechanical recharging. Two-electrode rechargeable batteries could be cycled
      stably for 180 cycles at 2 mA cm(-2). We also examine the activity of our carbon
      foam for both OER and ORR independently, in a three-electrode configuration, and
      discuss ways in which the Zn-air battery can be further improved. Finally, our
      density functional theory calculations reveal that the N,P co-doping and graphene
      edge effects are essential for the bifunctional electrocatalytic activity of our
      material.

PMID- 25849788
TI  - Nanoscale optical tomography with cathodoluminescence spectroscopy.
AB  - Tomography has enabled the characterization of the Earth's interior,
      visualization of the inner workings of the human brain, and three-dimensional
      reconstruction of matter at the atomic scale. However, tomographic techniques
      that rely on optical excitation or detection are generally limited in their
      resolution by diffraction. Here, we introduce a tomographic technique-
      cathodoluminescence spectroscopic tomography--to probe optical properties in
      three dimensions with nanometre-scale spatial and spectral resolution. We first
      obtain two-dimensional cathodoluminescence maps of a three-dimensional
      nanostructure at various orientations. We then use the method of filtered back
      projection to reconstruct the cathodoluminescence intensity at each wavelength.
      The resulting tomograms allow us to locate regions of efficient
      cathodoluminescence in three dimensions across visible and near-infrared
      wavelengths, with contributions from material luminescence and radiative decay of
      electromagnetic eigenmodes. The experimental signal can be further correlated
      with the radiative local density of optical states in particular regions of the
      reconstruction. We demonstrate how cathodoluminescence tomography can be used to
      achieve nanoscale three-dimensional visualization of light-matter interactions by
      reconstructing a three-dimensional metal-dielectric nanoresonator.

PMID- 25849789
TI  - Reversible oxygen scavenging at room temperature using electrochemically reduced
      titanium oxide nanotubes.
AB  - A material capable of rapid, reversible molecular oxygen uptake at room
      temperature is desirable for gas separation and sensing, for technologies that
      require oxygen storage and oxygen splitting such as fuel cells (solid-oxide fuel
      cells in particular) and for catalytic applications that require reduced oxygen
      species (such as removal of organic pollutants in water and oil-spill
      remediation). To date, however, the lowest reported temperature for a reversible
      oxygen uptake material is in the range of 200-300  degrees C, achieved in the
      transition metal oxides SrCoOx (ref. 1) and LuFe2O(4+x) (ref. 2) via thermal
      cycling. Here, we report rapid and reversible oxygen scavenging by Ti(2-x)
      nanotubes at room temperature. The uptake and release of oxygen is accomplished
      by an electrochemical rather than a standard thermal approach. We measure an
      oxygen uptake rate as high as 14 mmol O2 g(-1) min(-1), ~2,400 times greater than
      commercial, irreversible oxygen scavengers. Such a fast oxygen uptake at a
      remarkably low temperature suggests a non-typical mechanistic pathway for the re
      oxidation of Ti(2-x). Modelling the diffusion of oxygen, we show that a likely
      pathway involves 'exceptionally mobile' interstitial oxygen produced by the
      oxygen adsorption and decomposition dynamics, recently observed on the surface of
      anatase.

PMID- 25849790
TI  - Discolored ureteral stents: findings in urinalysis and urine culture.
AB  - OBJECTIVE: Discolored ureteral stents are sometimes encountered in daily clinical
      practice; however, the mechanism(s) underlying the development of discolored
      ureteral stents remain unknown. In this study, we retrospectively analyzed the
      characteristics of discolored ureteral stents based on the results of a
      urinalysis and urine culture. MATERIALS & METHODS: We identified a total of 26
      patients with discolored ureteral stents and compared the findings in the
      urinalyses and urine culture in 21 discolored versus 45 non-colored ureteral
      stents. RESULTS: The median and mean (+/- SD) duration of stenting time was 78.0
      and 81.3 (+/- 21.3) days for the discolored ureteral stents and 69.0 and 74.9 (+/
      19.8) days for the non-colored ureteral stents, respectively (P = 0.25). The
      discolored ureteral stents were associated with a higher mean urine pH than the
      non-colored ureteral stents (mean: 6.4 vs 6.0, P< 0.05). There were no
      significant differences between the two groups in the RBC (P = 0.51) and WBC (P =
      0.35) counts in the urinalyses. In addition, the rate of a positive culture in
      the patients with discolored stents [20 of 21 (95.2%)] was significantly (P
      <0.01) higher than that observed in the patients with non-colored ureteral stents
      [33 of 45 (73.3%)]. CONCLUSIONS: In this study, the subjects with discolored
      ureteral stents showed a significantly higher likelihood of having a positive
      urine culture and also demonstrated higher pH values in the urinalyses. However,
      no clear cut-off point to predict discoloration was indicated.

PMID- 25849791
TI  - Inhibition of PKCbeta2 overexpression ameliorates myocardial
      ischaemia/reperfusion injury in diabetic rats via restoring caveolin-3/Akt
      signaling.
AB  - Activation of PKCbeta (protein kinase Cbeta) plays a critical role in myocardial
      I/R (ischaemia/reperfusion) injury in non-diabetic rodents. In the myocardium of
      diabetes, PKCbeta2 overexpression is associated with increased vulnerability to
      post-ischaemic I/R injury with concomitantly impaired cardiomyocyte Cav
      (caveolin)-3 and Akt signalling compared with non-diabetic rats. We hypothesized
      that myocardial PKCbeta overexpression in diabetes exacerbates myocardial I/R
      injury through impairing Cav-3/Akt signalling. Streptozotocin-induced diabetic
      rats were treated with the selective PKCbeta inhibitor ruboxistaurin (RBX, 1
      mg/kg per day) for 4 weeks, starting from 1 week after diabetes induction, before
      inducing myocardial I/R achieved by occluding the left descending coronary artery
      followed by reperfusion. Cardiac function was measured using a pressure-volume
      conductance system. In an in vitro study, cardiac H9C2 cells were exposed to high
      glucose (30 mmol/l) and subjected to hypoxia followed by reoxygenation (H/R) in
      the presence or absence of the selective PKCbeta2 inhibitor CGP53353 (1 MUmol/l),
      siRNAs of PKCbeta2 or Cav-3 or Akt. Cell apoptosis and mitochondrial membrane
      potential were assessed by TUNEL (terminal deoxynucleotidyltransferase-mediated
      dUTP nick-end labelling) and JC-1 staining respectively. RBX significantly
      decreased post-ischaemic myocardial infarct size (35+/-5% compared with 49+/-3%
      in control, P<0.05) and attenuated cardiac dysfunction, and prevented the
      reduction in cardiac Cav-3 and enhanced phosphorylated/activated Akt (p-Akt) in
      diabetic rats (P<0.05). H/R increased cardiomyocyte injury under high glucose
      conditions as was evident by increased TUNEL-positive and increased JC-1
      monomeric cells (P<0.05 compared with control), accompanied with increased
      PKCbeta2 phosphorylation/activation and decreased Cav-3 expression. Either
      CGP53353 or PKCbeta2 siRNA significantly attenuated all of these changes and
      enhanced p-Akt. Cav-3 gene knockdown significantly reduced p-Akt and increased
      post-hypoxic cellular and mitochondrial injury despite a concomitant reduction in
      PKCbeta2 phosphorylation. PKCbeta2 inhibition with RBX protects diabetic hearts
      from myocardial I/R injury through Cav-3-dependent activation of Akt.

PMID- 25849792
TI  - Rhodium-catalysed synthesis of multi-substituted silylindenes from aryl alkynes
      and hydrosilanes via C-H bond activation.
AB  - We successfully developed rhodium-catalysed synthesis of multi-substituted
      silylindenes from 2 equivalents of aryl alkynes and 1 equivalent of hydrosilanes
      in moderate to good yields via C-H bond activation for the first time. The silyl
      groups of the obtained silylindenes could be converted to several other
      functional groups. 

PMID- 25849793
TI  - Probing ADAMTS13 substrate specificity using phage display.
AB  - Von Willebrand factor (VWF) is a large, multimeric protein that regulates
      hemostasis by tethering platelets to the subendothelial matrix at sites of
      vascular damage. The procoagulant activity of plasma VWF correlates with the
      length of VWF multimers, which is proteolytically controlled by the
      metalloprotease ADAMTS13. To probe ADAMTS13 substrate specificity, we created
      phage display libraries containing randomly mutated residues of a minimal
      ADAMTS13 substrate fragment of VWF, termed VWF73. The libraries were screened for
      phage particles displaying VWF73 mutant peptides that were resistant to
      proteolysis by ADAMTS13. These peptides exhibited the greatest mutation frequency
      near the ADAMTS13 scissile residues. Kinetic assays using mutant and wild-type
      substrates demonstrated excellent agreement between rates of cleavage for mutant
      phage particles and the corresponding mutant peptides. Cleavage resistance of
      selected mutations was tested in vivo using hydrodynamic injection of
      corresponding full-length expression plasmids into VWF-deficient mice. These
      studies confirmed the resistance to cleavage resulting from select amino acid
      substitutions and uncovered evidence of alternate cleavage sites and recognition
      by other proteases in the circulation of ADAMTS13 deficient mice. Taken together,
      these studies demonstrate the key role of specific amino acids residues including
      P3-P2' and P11', for substrate specificity and emphasize the importance in
      flowing blood of other ADAMTS13-VWF exosite interactions outside of VWF73. 

PMID- 25849794
TI  - The ABC exporter MsbA probed by solid state NMR - challenges and opportunities.
AB  - ATP binding cassette (ABC) transporters form a superfamily of integral membrane
      proteins involved in translocation of substrates across the membrane driven by
      ATP hydrolysis. Despite available crystal structures and extensive biochemical
      data, many open questions regarding their transport mechanisms remain. Therefore,
      there is a need to explore spectroscopic techniques such as solid state NMR in
      order to bridge the gap between structural and mechanistic data. In this study,
      we investigate the feasibility of using Escherichia coli MsbA as a model ABC
      transporter for solid state NMR studies. We show that optimised solubilisation
      and reconstitution procedures enable preparing stable and homogenous protein
      samples. Depending on the duration of solubilisation, MsbA can be obtained in
      either an apo- or in a native lipid A bound form. Building onto these
      optimisations, the first promising MAS-NMR spectra with narrow lines have been
      recorded. However, further sensitivity improvements are required so that complex
      NMR experiments can be recorded within a reasonable amount of time. We therefore
      demonstrate the usability of paramagnetic doping for rapid data acquisition and
      explore dynamic nuclear polarisation as a method for general signal enhancement.
      Our results demonstrate that solid state NMR provides an opportunity to address
      important biological questions related to complex mechanisms of ABC transporters.

PMID- 25849796
TI  - Are regulation-driven performance criteria still acceptable? - The German point
      of view.
AB  - Performance criteria should be a challenge for the laboratories to improve their
      quality. In countries with mandatory proficiency testing, the definition of
      performance criteria is a particular issue. If the definition of performance
      criteria is mandated from the regulatory bodies to medico-scientific
      institutions, scientific approaches (i.e., based on biological variation), the
      state-of-the-art approach (i.e., based on technical feasibility) as well as
      medical needs can be used to set up performance criteria such as the Richtlinie
      der Bundesarztekammer (RiliBAK; Guideline of the German Medical Association on
      Quality Assurance in Medical Laboratory Examinations) in Germany. The experiences
      with RiliBAK show that these performance criteria have to be revised on an
      ongoing basis. 

PMID- 25849795
TI  - Homeostatic control of biological membranes by dedicated lipid and membrane
      packing sensors.
AB  - Biological membranes are dynamic and complex assemblies of lipids and proteins.
      Eukaryotic lipidomes encompass hundreds of distinct lipid species and we have
      only begun to understand their role and function. This review focuses on recent
      advances in the field of lipid sensors and discusses methodical approaches to
      identify and characterize putative sensor domains. We elaborate on the role of
      integral and conditionally membrane-associated sensor proteins, their molecular
      mechanisms, and identify open questions in the emerging field of membrane
      homeostasis. 

PMID- 25849797
TI  - National survey on appropriateness of clinical biochemistry reporting in China.
AB  - BACKGROUND: Accurate and reliable testing reports play an important role in the
      prevention, diagnosis, treatment and prognosis of disease. However, little is
      known about the appropriateness of laboratory testing reporting in China. This
      national survey takes clinical biochemistry as an example to investigate the
      state of reporting appropriateness in our country. METHODS: An electronic
      questionnaire was sent to 1209 laboratories. The participants were asked to
      retrospectively evaluate the error rates of the following quality indicators:
      report template integrity, report content filling integrity, report delay, report
      recall, non-conformities between instrument and laboratory information system
      (LIS) data, non-conformities between report and request, report notification
      error, and report modification. Mann-Whitney and Kruskal-Wallis tests were used
      to identify the potential impacts of reporting appropriateness. RESULTS: A total
      of 662 of the 1209 laboratories (55%) submitted the survey results, with three
      returning incomplete data. For the integrity of the report, only 31% of the
      laboratories had a complete report template that contained all of 21 elements. In
      addition, the overall error rate of content filling integrity was 45.9% for
      19,770 pieces of reports. The overall sigma-values of other six quality
      indicators were all >4, and no significant difference was found among different
      departments. Group comparison suggested that reporting electronically had a
      better performance. CONCLUSIONS: The laboratory reporting system in China needs
      to improve, particularly the integrity of the report. Strengthening information
      technology will not only promote reporting appropriateness, but also guarantee
      accurate, standardized and traceable data collection and long-term monitoring.

PMID- 25849798
TI  - Comparison of splitting methods on survival tree.
AB  - We compare splitting methods for constructing survival trees that are used as a
      model of survival time based on covariates. A number of splitting criteria on the
      classification and regression tree (CART) have been proposed by various authors,
      and we compare nine criteria through simulations. Comparative studies have been
      restricted to criteria that suppose the survival model for each terminal node in
      the final tree as a non-parametric model. As the main results, the criteria using
      the exponential log-likelihood loss, log-rank test statistics, the deviance
      residual under the proportional hazard model, or square error of martingale
      residual are recommended when it appears that the data have constant hazard with
      the passage of time. On the other hand, when the data are thought to have
      decreasing hazard with passage of time, the criterion using the two-sample test
      statistic, or square error of deviance residual would be optimal. Moreover, when
      the data are thought to have increasing hazard with the passage of time, the
      criterion using the exponential log-likelihood loss, or impurity that combines
      observed times and the proportion of censored observations would be the best. We
      also present the results of an actual medical research to show the utility of
      survival trees. 

PMID- 25849799
TI  - Within-Subject Mediation Analysis in AB/BA Crossover Designs.
AB  - Crossover trials are widely used to assess the effect of a reversible exposure on
      an outcome of interest. To gain further insight into the underlying mechanisms of
      this effect, researchers may be interested in exploring whether or not it runs
      through a specific intermediate variable: the mediator. Mediation analysis in
      crossover designs has received scant attention so far and is mostly confined to
      the traditional Baron and Kenny approach. We aim to tackle mediation analysis
      within the counterfactual framework and elucidate the assumptions under which the
      direct and indirect effects can be identified in AB/BA crossover studies.
      Notably, we show that both effects are identifiable in certain statistical
      models, even in the presence of unmeasured time-independent (or upper-level)
      confounding of the mediator-outcome relation. Employing the mediation formula, we
      derive expressions for the direct and indirect effects in within-subject designs
      for continuous outcomes that lend themselves to linear modelling, under a large
      variety of settings. We discuss an estimation approach based on regressing
      differences in outcomes on differences in mediators and show how to allow for
      period effects as well as different types of moderation. The performance of this
      approach is compared to other existing methods through simulations and is
      illustrated with data from a neurobehavioural study. Lastly, we demonstrate how a
      sensitivity analysis can be performed that is able to assess the robustness of
      both the direct and indirect effect against violation of the "no unmeasured lower
      level mediator-outcome confounding" assumption. 

PMID- 25849800
TI  - A universal approximate cross-validation criterion for regular risk functions.
AB  - Selection of estimators is an essential task in modeling. A general framework is
      that the estimators of a distribution are obtained by minimizing a function (the
      estimating function) and assessed using another function (the assessment
      function). A classical case is that both functions estimate an information risk
      (specifically cross-entropy); this corresponds to using maximum likelihood
      estimators and assessing them by Akaike information criterion (AIC). In more
      general cases, the assessment risk can be estimated by leave-one-out cross
      validation. Since leave-one-out cross-validation is computationally very
      demanding, we propose in this paper a universal approximate cross-validation
      criterion under regularity conditions (UACVR). This criterion can be adapted to
      different types of estimators, including penalized likelihood and maximum a
      posteriori estimators, and also to different assessment risk functions, including
      information risk functions and continuous rank probability score (CRPS). UACVR
      reduces to Takeuchi information criterion (TIC) when cross-entropy is the risk
      for both estimation and assessment. We provide the asymptotic distributions of
      UACVR and of a difference of UACVR values for two estimators. We validate UACVR
      using simulations and provide an illustration on real data both in the
      psychometric context where estimators of the distributions of ordered categorical
      data derived from threshold models and models based on continuous approximations
      are compared. 

PMID- 25849801
TI  - The effect of Terminalia chebula extract vs. silver sulfadiazine on burn wounds
      in rats.
AB  - BACKGROUND: The aim of this study was to evaluate the efficacy of ethanol extract
      of Terminalia chebula in the treatment of hot water-induced burn wounds and to
      compare the results with silver sulfadiazine (SSD) in rats. METHODS: Five groups
      of ten rats were burned with hot water. Animals were administrated with topical
      cream at control, normal saline, 5%, 10% T. chebula extracts and standard SSD
      creams. Several parameters were assessed, including wound area, visual inspection
      of wound, bacteriology assessment, percentage of wound contraction and
      histopathological examination. RESULTS: The average area of wound on 10th day was
      11.2 +/- 3.3, 11 +/- 3.2, 8.5 +/- 2.3, 9.5 +/- 4.2 and 5.1 +/- 2.2 cm(2) for
      SSD1%, base cream, normal saline, herbal extract 5% and 10%, respectively. T.
      chebula 10% cream exhibited lower wound size than SSD1% and control groups at
      10th day post burn injury. On day 15, the percentage of wound contraction in T.
      chebula was 5% and 10% more than 18% and 53% in comparison to SSD1% group,
      respectively. Histopathological results exhibited well-formed horizontally
      oriented collagen fibers for appropriate tension. Strength of scar on burned
      tissue was better in T. chebula 5% and 10% as compared with control and SSD
      groups. CONCLUSIONS: The results of this study showed that T. chebula extract was
      capable of accelerating wound healing in rats by wound contraction, and had
      beneficial effects more than SSD 1% cream in the management of burn injury.

PMID- 25849802
TI  - Synthesis, characterization, crystal structure and antimicrobial activity of
      copper(II) complexes with the Schiff base derived from 2-hydroxy-4
      methoxybenzaldehyde.
AB  - A novel Schiff base, ethyl 4-[(E)-(2-hydroxy-4-methoxyphenyl)methylene
      amino]benzoate (HL), was prepared and structurally characterized on the basis of
      elemental analyses, (1)H NMR, (13)C NMR, UV-Vis and IR spectral data. Six new
      copper(II) complexes, [Cu(L)(NO3)(H2O)2] (1), [Cu(L)2] (2), [Cu(L)(OAc)] (3),
      [Cu2 (L)2Cl2(H2O)4] (4), [Cu(L)(ClO4)(H2O)] (5) and [Cu2(L2S)(ClO4)(H2O)]ClO4.H2O
      (6) have been synthesized. The characterization of the newly formed compounds was
      done by IR, UV-Vis, EPR, FAB mass spectroscopy, elemental and thermal analysis,
      magnetic susceptibility measurements and molar electric conductivity. The crystal
      structures of Schiff base and the complex [Cu2(L2S)(ClO4)(H2O)]ClO4.H2O (6) have
      been determined by single crystal X-ray diffraction studies. Both copper atoms
      display a distorted octahedral coordination type [O4NS]. This coordination is
      ensured by three phenol oxygen, two of which being related to the u-oxo-bridge,
      the nitrogen atoms of the azomethine group and the sulfur atoms that come from
      the polydentate ligand. The in vitro antimicrobial activity against Escherichia
      coli ATCC 25922, Salmonella enteritidis, Staphylococcus aureus ATCC 25923,
      Enterococcus and Candida albicans strains was studied and compared with that of
      free ligand. The complexes 1, 2, 5 showed a better antimicrobial activity than
      the Schiff base against the tested microorganisms.

PMID- 25849803
TI  - X-ray structures of precursors of styrylpyridine-derivatives used to obtain 4
      ((E)-2-(pyridin-2-yl)vinyl)benzamido-TEMPO: synthesis and characterization.
AB  - The synthesis and characterization of the precursor isomers trans-4-(2-(pyridin-2
      yl)vinylbenzaldehyde (I), trans-4-(2-(pyridin-4-yl)vinylbenzaldehyde (II), trans
      4-(2-(pyridin-2-yl)vinylbenzoic acid (III) and (E)-4-(2-(pydridin-4
      yl)vinylbenzoic acid (IV) are reported. These compounds were prepared in order to
      obtain trans-4-((E)-2-(pyridin-2-yl)vinyl)benzamide-TEMPO (V). Compounds I and II
      were obtained by using a Knoevenagel reaction in the absence of a condensing
      agent and solvent. Oxidation of the aldehyde group using the Jones reagent
      afforded the corresponding acid forms III and IV. A condensation reaction with 4
      amino-TEMPO using oxalyl chloride/DMF/CH2Cl2 provided the 4-((E)-2-(pyridin-2
      yl)vinyl)benzamide-TEMPO. Single crystals of compounds I, II and III were
      obtained and characterized by X-ray diffraction. Compound I belongs to space
      group P2(1)/c, a = 12.6674(19) A, b = 7.2173(11) A, c = 11.5877(14) A, b =
      97.203(13) degrees  and the asymmetric unit was Z = 4, whereas compound II was in
      the space group P2(1), with a = 3.85728(9) A, b = 10.62375(19) A, c = 12.8625(2)
      A, b = 91.722 (2) degrees  and the asymmetric unit was Z = 2. Compound III
      crystallized as single colorless needle crystals, belonging to the monoclinic
      system with space group P2(1), with Z = 2, with a = 3.89359(7) A, b = 17.7014(3)
      A, c = 8.04530(12) A, b = 94.4030 (16) degrees . All compounds were completely
      characterized by IR, (1)H-NMR, EI-MS and UV-Vis.

PMID- 25849804
TI  - Characterization at 25  degrees C of sodium hyaluronate in aqueous solutions
      obtained by transport techniques.
AB  - Mutual diffusion coefficients, D, were determined for aqueous solutions of sodium
      hyaluronate (NaHy) at 25  degrees C and concentrations ranging from 0.00 to 1.00
      g.dm(-3) using the Taylor dispersion technique. From these experimental data, it
      was possible to estimate some parameters, such as the hydrodynamic radius Rh, and
      the diffusion coefficient at infinitesimal concentration, D0, of hyaluronate ion,
      permitting us to have a better understanding of the structure of these systems of
      sodium hyaluronate in aqueous solutions. The additional viscosity measurements
      were done and Huggins constant, kH, and limiting viscosity number, [eta], were
      computed for interaction NaHy/water and NaHy/NaHy determination.

PMID- 25849805
TI  - Three new pigment protein tyrosine phosphatases inhibitors from the insect
      parasite fungus Cordyceps gracilioides: terreusinone A, pinophilin C and
      cryptosporioptide A.
AB  - Three new pigment compounds--terreusinone A (1), pinophilin C (2) and
      cryptosporioptide A (3)-were isolated from a solid culture of Cordyceps
      gracilioides. The structures of these compounds were determined by extensive
      spectroscopic analysis including HRESIMS, 1D- and 2D-NMR. The structure of
      terreusinone A (1) was further confirmed by single-crystal X-ray crystallographic
      diffraction analysis. In an in vitro activity assay, 1, 2 and 3 exhibited high
      inhibitory activity against PTP1B, SHP2, CDC25B, LAR and SHP1. Terreusinone A (1)
      inhibited PTP1B, SHP2, CDC25B, LAR and SHP1 enzyme with IC50 values 12.5, >50,
      4.1, 10.6, 5.6 ug/mL, respectively; pinophilin C (2) with IC50 values 6.8, 8.0,
      4.5, 4.7, 3.4 ug/mL, respectively; and cryptosporioptide A (3) with IC50 values
      7.3, 5.7, 7.6, >50, 4.9 ug/mL, respectively.

PMID- 25849806
TI  - Anisotropy in bone demineralization revealed by polarized far-IR spectroscopy.
AB  - Bone material is composed of an organic matrix of collagen fibers and apatite
      nanoparticles. Previously, vibrational spectroscopy techniques such as infrared
      (IR) and Raman spectroscopy have proved to be particularly useful for
      characterizing the two constituent organic and inorganic phases of bone. In this
      work, we tested the potential use of high intensity synchrotron-based far-IR
      radiation (50-500 cm(-1)) to gain new insights into structure and chemical
      composition of bovine fibrolamellar bone. The results from our study can be
      summarized in the following four points: (I) compared to far-IR spectra obtained
      from synthetic hydroxyapatite powder, those from fibrolamellar bone showed
      similar peak positions, but very different peak widths; (II) during stepwise
      demineralization of the bone samples, there was no significant change neither to
      far-IR peak width nor position, demonstrating that mineral dissolution occurred
      in a uniform manner; (III) application of external loading on fully demineralized
      bone had no significant effect on the obtained spectra, while dehydration of
      samples resulted in clear differences. (IV) using linear dichroism, we showed
      that the anisotropic structure of fibrolamellar bone is also reflected in
      anisotropic far-IR absorbance properties of both the organic and inorganic
      phases. Far-IR spectroscopy thus provides a novel way to functionally
      characterize bone structure and chemistry, and with further technological
      improvements, has the potential to become a useful clinical diagnostic tool to
      better assess quality of collagen-based tissues.

PMID- 25849808
TI  - Unique photophysical properties of 9-styryl-1,2-dihydropyrrolo[3,4-beta]indolizin
      3-one and its efficient synthesis via direct C-H activation.
AB  - A styryl Seoul-Fluor (SF) skeleton was rationally designed by introducing an
      olefin unit at the C-9 of 1,2-dihydropyrrolo[3,4-beta]indolizin-3-one via
      regioselective direct C-H activation. We synthesized a series of styryl SF
      analogues, maintaining unique photophysical properties that can be systematically
      controlled by the electronic characteristics of the substituents, with an average
      bathochromic shift of 39 nm in emission maxima. 

PMID- 25849807
TI  - Assessment of brainstem function with auricular branch of vagus nerve stimulation
      in Parkinson's disease.
AB  - BACKGROUND: The efferent dorsal motor nucleus of the vagal nuclei complex may
      degenerate early in the course of Parkinson's disease (PD), while efferent
      nucleus ambiguous, the principal source of parasympathetic vagal neurons
      innervating the heart, and afferent somatosensory nuclei remain intact.
      OBJECTIVE: To obtain neurophysiological evidence related to this pattern, we
      tested processing of afferent sensory information transmitted via the auricular
      branch of the vagus nerve (ABVN) which is known to be connected to autonomic
      regulation of cardiac rhythm. METHODS: In this cross-sectional observational
      study, we recorded (i) somatosensory evoked potentials (ABVN-SEP) and (ii)
      cutaneo-cardioautonomic response elicited by stimulation of the ABVN (modulation
      of heart-rate variability (HRV index; low frequency power, ln(LF), high frequency
      power, ln(HF); ln(LF/HF) ratio)) in 50 PD patients and 50 age and sex matched
      healthy controls. Additionally, auditory evoked potentials and trigeminal nerve
      SEP were assessed. RESULTS: Neither ABVN-SEP nor any of the other functional
      brainstem parameters differed between patients and controls. Although HRV index
      was decreased in PD patients, modulation of ln(LF/HF) by ABVN-stimulation, likely
      indicating cardiac parasympathetic activation, did not differ between both
      groups. CONCLUSIONS: Findings do not point to prominent dysfunction of processing
      afferent information from ABVN and its connected parasympathetic cardiac pathway
      in PD. They are consistent with the known pattern of degeneration of the vagal
      nuclei complex of the brainstem.

PMID- 25849809
TI  - Clinical outcomes of early and later physical therapist services for older adults
      with back pain.
AB  - BACKGROUND CONTEXT: The timing of physical therapy (PT) services and its
      association with later function and pain are not clear, especially in older
      adults. PURPOSE: The purpose of this study was to compare clinical outcomes of
      patients receiving early or later PT services with those not receiving PT among
      older adults presenting to primary care for a new visit for back pain. STUDY
      DESIGN/SETTING: Prospective cohort study using the Back Pain Outcomes Using
      Longitudinal Data registry. PATIENT SAMPLE: A total of 3,705 adults 65 years and
      older with a new visit for back pain were included. OUTCOME MEASURES: The outcome
      measures were Roland-Morris Disability Questionnaire (RMDQ), Pain Numerical
      Rating Scales, and EuroQol-5D. METHODS: We studied two phases of PT utilization:
      early (0-28 days) and later (3-6 months). At baseline, we selected the
      participants with complete 12 months of patient-reported outcomes and electronic
      medical record data. Early PT was defined as initiating PT less than or equal to
      28 days from the index visit for back pain. The no early PT group consisted of
      patients with no PT, no injections, no surgery, and no chiropractic within 28
      days. We restricted the later phase analysis to patients with pain greater than 2
      of 10 and an RMDQ score greater than 4 to create a subsample of patients with
      continuing clinically important back pain. We defined later PT as initiating PT
      between 3 and 6 months after the index visit. The no later PT group consisted of
      patients without any PT during this time. We used propensity score matching
      followed by multiple linear regression to estimate the mean difference in
      outcome. Sensitivity analysis examined clinically important change and dose of PT
      use among the early PT group. RESULTS: The early PT group had better functional
      status with an adjusted mean RMDQ of 1.1 points less than the no early PT group
      (95% confidence interval: -2.2, -0.1) and less back pain of -0.5 (-0.9, -0.1) at
      12 months. There was no difference between early PT groups at 3 and 6 months. The
      odds of a 30% improvement in function or pain were not different between these
      matched groups at 12 months, but the early PT group had increased odds of a 50%
      improvement in function at 12 months (odds ratio: 1.58, 95% confidence interval:
      1.04, 2.40). There was no difference between later groups at 12 months. Greater
      dose of PT use within the early PT group was associated with better functional
      status (p= .01). CONCLUSIONS: We found that among older adults presenting to
      their primary care providers for a new episode of back pain, early referral to PT
      resulted in no or minimal differences in pain, function, or health-related
      quality at 3, 6, or 12 months compared with a matched group that did not receive
      early PT. Secondary analysis show that patients initiating early PT may be
      somewhat more likely to experience 50% improvement in function at 12 months.

PMID- 25849810
TI  - Lady Liberty and Godfather Death as candidates for linguistic relativity?
      Scrutinizing the gender congruency effect on personified allegories with explicit
      and implicit measures.
AB  - Linguistic relativity--the idea that language affects thought by way of its
      grammatical categorizations--has been controversially debated for decades. One of
      the contested cases is the grammatical gender of nouns, which is claimed to
      affect how their referents are conceptualized (i.e., as rather female or male in
      congruence with the grammatical gender of the noun), especially when used
      allegorically. But is this association strong enough to be detected in implicit
      measures, and, if so, can we disentangle effects of grammatical gender and
      allegorical association? Three experiments with native speakers of German tackled
      these questions. They revealed a gender congruency effect on allegorically used
      nouns, but this effect was stronger with an explicit measure (assignment of
      biological sex) than with an implicit measure (Extrinsic Affective Simon Task)
      and disappeared in the implicit measure when grammatical gender and allegorical
      associations were set into contrast. Taken together, these findings indicate that
      the observed congruency effect was driven by the association of nouns with
      personifications rather than by their grammatical gender. In conclusion, we also
      discuss implications of these findings for linguistic relativity.

PMID- 25849811
TI  - Erratum: Allergic diseases and asthma in the family predict the persistence and
      onset-age of asthma: a prospective cohort study.

PMID- 25849812
TI  - Combining the sterile insect technique with the incompatible insect technique: I
      impact of wolbachia infection on the fitness of triple- and double-infected
      strains of Aedes albopictus.
AB  - The mosquito species Aedes albopictus is a major vector of the human diseases
      dengue and chikungunya. Due to the lack of efficient and sustainable methods to
      control this mosquito species, there is an increasing interest in developing and
      applying the sterile insect technique (SIT) and the incompatible insect technique
      (IIT), separately or in combination, as population suppression approaches. Ae.
      albopictus is naturally double-infected with two Wolbachia strains, wAlbA and
      wAlbB. A new triple Wolbachia-infected strain (i.e., a strain infected with
      wAlbA, wAlbB, and wPip), known as HC and expressing strong cytoplasmic
      incompatibility (CI) in appropriate matings, was recently developed. In the
      present study, we compared several fitness traits of three Ae. albopictus strains
      (triple-infected, double-infected and uninfected), all of which were of the same
      genetic background ("Guangzhou City, China") and were reared under the same
      conditions. Investigation of egg-hatching rate, survival of pupae and adults, sex
      ratio, duration of larval stages (development time from L1 to pupation), time to
      emergence (development time from L1 to adult emergence), wing length, female
      fecundity and adult longevity indicated that the presence of Wolbachia had only a
      minimal effect on host fitness. Based on this evidence, the HC strain is
      currently under consideration for mass rearing and application in a combined SIT
      IIT strategy to control natural populations of Ae. albopictus in mainland China. 

PMID- 25849813
TI  - Single bacteria movement tracking by online microscopy--a proof of concept study.
AB  - In this technical report we demonstrate a low-cost online unit allowing movement
      tracking of flagellated bacteria on a single-cell level during fermentation
      processes. The system's ability to distinguish different metabolic states
      (viability) of bacteria by movement velocity was investigated. A flow-through
      cuvette with automatically adjustable layer thickness was developed. The cuvette
      can be used with most commercially available laboratory microscopes equipped with
      40* amplification and a digital camera. In addition, an automated sample
      preparation unit and a software module was developed measuring size, moved
      distance, and speed of bacteria. In a proof of principle study the movement
      velocities of Bacillus amyloliquefaciens FZB42 during three batch fermentation
      processes were investigated. In this process the bacteria went through different
      metabolic states, vegetative growth, diauxic shift, vegetative growth after
      diauxic shift, and sporulation. It was shown that the movement velocities during
      the different metabolic states significantly differ from each other. Therefore,
      the described setup has the potential to be used as a bacteria viability
      monitoring tool. In contrast to some other techniques, such as electro-optical
      techniques, this method can even be used in turbid production media. 

PMID- 25849814
TI  - Functional gene composition, diversity and redundancy in microbial stream biofilm
      communities.
AB  - We surveyed the functional gene composition and diversity of microbial biofilm
      communities in 18 New Zealand streams affected by different types of catchment
      land use, using a comprehensive functional gene array, GeoChip 3.0. A total of
      5,371 nutrient cycling and energy metabolism genes within 65 gene families were
      detected among all samples (342 to 2,666 genes per stream). Carbon cycling genes
      were most common, followed by nitrogen cycling genes, with smaller proportions of
      sulphur, phosphorus cycling and energy metabolism genes. Samples from urban and
      native forest streams had the most similar functional gene composition, while
      samples from exotic forest and rural streams exhibited the most variation. There
      were significant differences between nitrogen and sulphur cycling genes detected
      in native forest and urban samples compared to exotic forest and rural samples,
      attributed to contrasting proportions of nitrogen fixation, denitrification, and
      sulphur reduction genes. Most genes were detected only in one or a few samples,
      with only a small minority occurring in all samples. Nonetheless, 42 of 65 gene
      families occurred in every sample and overall proportions of gene families were
      similar among samples from contrasting streams. This suggests the existence of
      functional gene redundancy among different stream biofilm communities despite
      contrasting taxonomic composition. 

PMID- 25849815
TI  - Associations between ultrasound measures of abdominal fat distribution and
      indices of glucose metabolism in a population at high risk of type 2 diabetes:
      the ADDITION-PRO study.
AB  - AIMS: Visceral adipose tissue measured by CT or MRI is strongly associated with
      an adverse metabolic risk profile. We assessed whether similar associations can
      be found with ultrasonography, by quantifying the strength of the relationship
      between different measures of obesity and indices of glucose metabolism in a
      population at high risk of type 2 diabetes. METHODS: A cross-sectional analysis
      of 1342 participants of the ADDITION-PRO study. We measured visceral adipose
      tissue and subcutaneous adipose tissue with ultrasonography, anthropometrics and
      body fat percentage by bioelectrical impedance. Indices of glucose metabolism
      were derived from a three point oral glucose tolerance test. Linear regression of
      obesity measures on indices of glucose metabolism was performed. RESULTS: Mean
      age was 66.2 years, BMI 26.9kg/m2, subcutaneous adipose tissue 2.5cm and visceral
      adipose tissue 8.0cm. All measures of obesity were positively associated with
      indicators of glycaemia and inversely associated with indicators of insulin
      sensitivity. Associations were of equivalent magnitude except for subcutaneous
      adipose tissue and the visceral/subcutaneous adipose tissue ratio, which showed
      weaker associations. One standard deviation difference in BMI, visceral adipose
      tissue, waist circumference, waist/height ratio and body fat percentage
      corresponded approximately to 0.2mmol/l higher fasting glucose, 0.7mmol/l higher
      2-hr glucose, 0.06-0.1% higher HbA1c, 30 % lower HOMA index of insulin
      sensitivity, 20% lower Gutt's index of insulin sensitivity, and 100 unit higher
      Stumvoll's index of beta-cell function. After adjustment for waist circumference
      visceral adipose tissue was still significantly associated with glucose
      intolerance and insulin resistance, whereas there was a trend towards inverse or
      no associations with subcutaneous adipose tissue. After adjustment, a 1cm
      increase in visceral adipose tissue was associated with ~5% lower insulin
      sensitivity (p<=0.0004) and ~0.18mmol/l higher 2-hr glucose (p<=0.001).
      CONCLUSION: Visceral and subcutaneous adipose tissue assessed by ultrasonography
      are significantly associated with glucose metabolism, even after adjustment for
      other measures of obesity.

PMID- 25849817
TI  - Effect of kumquat (Fortunella crassifolia) pericarp on natural killer cell
      activity in vitro and in vivo.
AB  - Natural killer (NK) cells play a key role in innate immune defense against
      infectious disease and cancer. A reduction of NK activity is likely to be
      associated with increased risk of these types of disease. In this study, we
      investigate the activation potential of kumquat pericarp acetone fraction (KP-AF)
      on NK cells. It is shown to significantly increase IFN-gamma production and NK
      cytotoxic activity in human KHYG-1 NK cells. Moreover, oral administration of KP
      AF significantly improves both suppressed plasma IFN-gamma levels and NK
      cytotoxic activity per splenocyte in restraint-stressed mice. These results
      indicate that raw kumquat pericarp activates NK cells in vitro and in vivo. To
      identify the active constituents, we also examined IFN-gamma production on KHYG-1
      cells by the predicted active components. Only beta-cryptoxanthin increased IFN
      gamma production, suggesting that NK cell activation effects of KP-AF may be
      caused by carotenoids such as beta-cryptoxanthin. 

PMID- 25849816
TI  - Less pollen-mediated gene flow for more signatures of glacial lineages: congruent
      evidence from balsam fir cpDNA and mtDNA for multiple refugia in eastern and
      central North America.
AB  - The phylogeographic structure and postglacial history of balsam fir (Abies
      balsamea), a transcontinental North American boreal conifer, was inferred using
      mitochondrial DNA (mtDNA) and chloroplast DNA (cpDNA) markers. Genetic structure
      among 107 populations (mtDNA data) and 75 populations (cpDNA data) was analyzed
      using Bayesian and genetic distance approaches. Population differentiation was
      high for mtDNA (dispersed by seeds only), but also for cpDNA (dispersed by seeds
      and pollen), indicating that pollen gene flow is more restricted in balsam fir
      than in other boreal conifers. Low cpDNA gene flow in balsam fir may relate to
      low pollen production due to the inherent biology of the species and populations
      being decimated by recurrent spruce budworm epidemics, and/or to low dispersal of
      pollen grains due to their peculiar structural properties. Accordingly, a
      phylogeographic structure was detected using both mtDNA and cpDNA markers and
      population structure analyses supported the existence of at least five
      genetically distinct glacial lineages in central and eastern North America. Four
      of these would originate from glacial refugia located south of the Laurentide ice
      sheet, while the last one would have persisted in the northern Labrador region.
      As expected due to reduced pollen-mediated gene flow, congruence between the
      geographic distribution of mtDNA and cpDNA lineages was higher than in other
      North American conifers. However, concordance was not complete, reflecting that
      restricted but nonetheless detectable cpDNA gene flow among glacial lineages
      occurred during the Holocene. As a result, new cpDNA and mtDNA genome
      combinations indicative of cytoplasmic genome capture were observed. 

PMID- 25849818
TI  - Organoselenium-catalyzed, hydroxy-controlled regio- and stereoselective amination
      of terminal alkenes: efficient synthesis of 3-amino allylic alcohols.
AB  - An efficient route to prepare 3-amino allylic alcohols in excellent regio- and
      stereoselectivity in the presence of bases by orangoselenium catalysis has been
      developed. In the absence of bases alpha,beta-unsaturated aldehydes were formed
      in up to 97% yield. Control experiments reveal that the hydroxy group is crucial
      for the direct amination. 

PMID- 25849819
TI  - Projected effect of increased active travel in German urban regions on the risk
      of type 2 diabetes.
AB  - BACKGROUND: Future transportation policy is likely to reduce emissions in the
      cities and urban regions by strengthening active travel. Increased walking and
      cycling are known to have positive effects on health outcomes. This work
      estimates effects of increased active travel on type 2 diabetes in Germany, where
      64% of the population live in urban regions. METHODS: Based on the effect size of
      an increased active travel scenario reported from a recent meta-analysis, we
      project the change in the life time risk, the proportion of prevented cases and
      the change in diabetes free life time in a German birth cohort (born 1985)
      compared to business as usual. RESULTS: The absolute risk reduction of developing
      type 2 diabetes before the age of 80 is 6.4% [95% confidence interval: 3.7-9.7%]
      for men and 4.7% [2.2-7.7%] for women, respectively. Compared to business as
      usual, the increased active travel scenario prevents 14.0% [8.1-21.2%] of the
      future cases of diabetes in men and 15.8% [9.3-23.1%] in women. Diabetes free
      survival increases by 1.7 [1.0-2.7] years in men and 1.4 [0.6-2.3] in women.
      CONCLUSIONS: Our projection predicts a substantial impact of increased active
      travel on the future burden of type 2 diabetes. The most striking effect may be
      seen in the number of prevented cases. In all urban regions with an increased
      active travel transport policy, about one out of seven male and one out of six
      female cases can be prevented.

PMID- 25849821
TI  - Revision of biological methods for determination of EDC presence and their
      endocrine potential.
AB  - Endocrine-disrupting compounds (EDC) are chemicals responsible for disturbances
      in the hormonal balance of organisms. This group of chemicals includes both
      egzogenic and endogenic substances or their mixtures that impact functioning of
      natural hormones in organisms. In the available literature one can find
      information on the application of chromatographic and related techniques in the
      analysis of environmental samples for detection, identification, and quantitation
      of a wide spectrum of chemicals posing endocrine properties. On the other hand,
      more and more biotests are being developed to determine endocrine potency of
      environmental samples due to development of genetic engineering methods and
      specific detection methods of cells' response to the action of particular
      chemicals of interest. This article presents revisions of the most novel methods
      for this potency determination with application to biological elements. 

PMID- 25849822
TI  - Application of gas chromatography to analysis of spirit-based alcoholic
      beverages.
AB  - Spirit-based beverages are alcoholic drinks; their production processes are
      dependent on the type and origin of raw materials. The composition of this
      complex matrix is difficult to analyze, and scientists commonly choose gas
      chromatography techniques for this reason. With a wide selection of extraction
      methods and detectors it is possible to provide qualitative and quantitative
      analysis for many chemical compounds with various functional groups. This article
      describes different types of gas chromatography techniques and their most
      commonly used associated extraction techniques (e.g., LLE, SPME, SPE, SFE, and
      SBME) and detectors (MS, TOFMS, FID, ECD, NPD, AED, O or EPD). Additionally,
      brief characteristics of internationally popular spirit-based beverages and
      application of gas chromatography to the analysis of selected alcoholic drinks
      are presented. 

PMID- 25849823
TI  - Chromatographic methods for analysis of triazine herbicides.
AB  - Gas chromatography (GC) and high-performance liquid chromatography (HPLC) coupled
      to different detectors, and in combination with different sample extraction
      methods, are most widely used for analysis of triazine herbicides in different
      environmental samples. Nowadays, many variations and modifications of extraction
      and sample preparation methods such as solid-phase microextraction (SPME), hollow
      fiber-liquid phase microextraction (HF-LPME), stir bar sportive extraction
      (SBSE), headspace-solid phase microextraction (HS-SPME), dispersive liquid-liquid
      microextraction (DLLME), dispersive liquid-liquid microextraction based on
      solidification of floating organic droplet (DLLME-SFO), ultrasound-assisted
      emulsification microextraction (USAEME), and others have been introduced and
      developed to obtain sensitive and accurate methods for the analysis of these
      hazardous compounds. In this review, several analytical properties such as
      linearity, sensitivity, repeatability, and accuracy for each developed method are
      discussed, and excellent results were obtained for the most of developed methods
      combined with GC and HPLC techniques for the analysis of triazine herbicides.
      This review gives an overview of recent publications of the application of GC and
      HPLC for analysis of triazine herbicides residues in various samples. 

PMID- 25849824
TI  - "Why not stoichiometry" versus "Stoichiometry--why not?" Part II: GATES in
      context with redox systems.
AB  - Redox equilibria and titration play an important role in chemical analysis, and
      the formulation of an accurate mathematical description is a challenge. This
      article is devoted to static and (mainly) dynamic redox systems; the dynamic
      systems are represented by redox titrations. An overview addresses earlier
      approaches to static redox systems (redox diagram plots, including Pourbaix
      diagrams) and to titration redox systems, thereby covering a gap in the
      literature. After this short review, the generalized approach to electrolytic
      systems (GATES) is introduced, with generalized electron balance (GEB) as its
      inherent part within GATES/GEB. Computer simulation, performed according to
      GATES/GEB, enables following the changes in potential and pH of the solution,
      together with chemical speciation at each step of a titration, thus providing
      better insight into this procedure. The undeniable advantages of GATES/GEB over
      earlier approaches are indicated. Formulation of GEB according to two approaches
      (I and II) is presented on the respective examples. A general criterion
      distinguishing between non-redox and redox systems is presented. It is indicated
      that the formulation of GEB according to Approach II does not need the knowledge
      of oxidation degrees of particular elements; knowledge of the composition,
      expressed by chemical formula of the species and its charge, is sufficient for
      this purpose. Approach I to GEB, known also as the "short" version of GEB, is
      applicable if oxidation degrees for all elements of the system are known
      beforehand. The roles of oxidants and reductants are not ascribed to particular
      components forming a system and to the species thus formed. This is the complete
      opposite of earlier approaches to redox titrations, based on the stoichiometric
      redox reaction, formulated for this purpose. GEB, perceived as a law of matter
      conservation, is fully compatible with other (charge and concentration) balances
      related to the system in question. The applicability of GATES/GEB in optimization
      a priori of chemical analyses made with use of redox titration is indicated. The
      article is illustrated with many examples of static and dynamic redox systems.
      The related plots are obtained from calculations made according to iterative
      computer programs. This way, GATES/GEB enables seeing details invisible in real
      experiments. 

PMID- 25849825
TI  - Magnetic solid-phase extraction based on modified ferum oxides for enrichment,
      preconcentration, and isolation of pesticides and selected pollutants.
AB  - Recently, a simple, rapid, high-efficiency, selective, and sensitive method for
      isolation, preconcentration, and enrichment of analytes has been developed. This
      new method of sample handling is based on ferum oxides as magnetic nanoparticles
      (MNPs) and has been used for magnetic solid-phase extraction (MSPE) of various
      analytes from various matrices. This review focuses on the applications of
      modified ferum oxides, especially modified Fe3O4 MNPs, as MSPE adsorbent for
      pesticide isolation from various matrices. Further perspectives on MSPE based on
      modified Fe3O4 for inorganic metal ions, organic compounds, and biological
      species from water samples are also presented. Ferum(III) oxide MNPs (Fe2O3) are
      also highlighted. 

PMID- 25849826
TI  - The level of residual dispersion variation and the power of differential
      expression tests for RNA-Seq data.
AB  - RNA-Sequencing (RNA-Seq) has been widely adopted for quantifying gene expression
      changes in comparative transcriptome analysis. For detecting differentially
      expressed genes, a variety of statistical methods based on the negative binomial
      (NB) distribution have been proposed. These methods differ in the ways they
      handle the NB nuisance parameters (i.e., the dispersion parameters associated
      with each gene) to save power, such as by using a dispersion model to exploit an
      apparent relationship between the dispersion parameter and the NB mean.
      Presumably, dispersion models with fewer parameters will result in greater power
      if the models are correct, but will produce misleading conclusions if not. This
      paper investigates this power and robustness trade-off by assessing rates of
      identifying true differential expression using the various methods under
      realistic assumptions about NB dispersion parameters. Our results indicate that
      the relative performances of the different methods are closely related to the
      level of dispersion variation unexplained by the dispersion model. We propose a
      simple statistic to quantify the level of residual dispersion variation from a
      fitted dispersion model and show that the magnitude of this statistic gives hints
      about whether and how much we can gain statistical power by a dispersion-modeling
      approach. 

PMID- 25849827
TI  - Evaluation of genetic polymorphisms in clusterin and tumor necrosis factor-alpha
      genes in South Indian individuals with pseudoexfoliation syndrome.
AB  - PURPOSE: The aim of this study was to explore the potential association of
      genetic variants across clusterin (CLU) and tumor necrosis factor-alpha (TNF
      alpha) genes in South Indian individuals with pseudoexfoliation syndrome (PEXS)
      and pseudoexfoliation glaucoma (PEXG). MATERIALS AND METHODS: A total of 523
      individuals including 299 unrelated cases (150 PEXS and 149 PEXG) and 224 age-
      and ethnically-matched healthy controls were recruited for genetic analysis. Six
      single-nucleotide polymorphisms (SNPs) including, five CLU SNPs (rs11136000,
      rs2279590, rs9331888, rs9331931, rs3087554) and one promoter SNP (rs1800629) of
      TNF-alpha were genotyped in all study subjects. Genotyping of CLU SNPs were
      performed using the TaqMan allelic discrimination assay while TNF-alpha SNP was
      genotyped using polymerase chain reaction (PCR)-based restriction fragment length
      polymorphism (RFLP) analysis. Association analysis was performed by determining
      the distributions of genotype and allele frequencies, Hardy-Weinberg equilibrium,
      and chi-square p values and odds ratios as implemented in the Golden Helix SNP &
      Variation Suite (SVS). RESULTS: Five CLU SNPs did not show any significant
      differences in allele frequencies between patients and control subjects
      (rs3087554, p = 0.919, OR = 1.01, 95% CI: 0.77-1.33; rs2279590, p = 0.432, OR =
      1.12, 95% CI: 0.84-1.51; rs9331931, p = 0.310, OR = 1.24, 95% CI: 0.81-1.89;
      rs11136000, p = 0.072, OR = 1.31, 95% CI: 0.97-1.76; rs9331888, p = 0.911, OR =
      1.01, 95% CI: 0.78-1.31). The investigation of TNF-alpha SNP established a
      significant association with PEXS and PEXG (p = 0.042, OR = 0.61, 95% CI: 0.38
      0.99). However, this association did not remain significant after Bonferroni
      correction. CONCLUSIONS: Our data suggest that genetic variants in CLU and TNF
      alpha genes do not play a major role in the development of PEXS and PEXG in the
      South Indian population.

PMID- 25849828
TI  - HIV-1 vaccines based on replication-competent Tiantan vaccinia protected Chinese
      rhesus macaques from simian HIV infection.
AB  - OBJECTIVE: To assess the efficacy of HIV vaccines constructed from replication
      competent Tiantan vaccinia virus (rTV) alone or combined with DNA in protecting
      Chinese rhesus macaques from homologous Simian/Human Immunodeficiency Virus
      (SHIV)-CN97001 challenge. METHODS: The nef, gag, pol, and gp140 genes from strain
      CRF07_BC HIV-1 CN54 were selected to construct an HIV vaccine using the rTV or
      rTV/DNA vaccine. After vaccination, the vaccine and control groups were
      intravenously challenged with SHIV-CN97001 (32 MID50). HIV-specific antibodies
      and neutralizing antibodies, gp70 V1V2 binding antibodies, and cytotoxic T
      lymphocyte responses were measured prospectively after vaccination with an ELISA,
      a virus infectivity assay in TZM-bl cells, and ELISPOT assays, respectively.
      Viral RNA was quantified after challenge with real-time reverse transcriptase-PCR
      (RT-PCR), and protection efficacy was determined with an analysis of CD8
      lymphocyte depletion in vivo. RESULTS: Both rTV and DNA/rTV vaccine groups
      developed strong cellular and humoral responses against HIV-1 CN54 antigens,
      including Gag and Env, and also developed significant and persistent anti-Env
      antibodies and neutralizing antibodies after immunization. Both the rTV and
      DNA/rTV groups were significantly protected against SHIV-CN97001 or displayed
      lower viremia than the controls. After CD8 lymphocyte depletion, no viremia was
      detectable in the vaccinated monkeys, but rebounded rapidly in the control
      animals. Protection against infection correlated with vaccine-elicited
      neutralizing antibodies specific for homologous HIV-1 viruses. CONCLUSION: An rTV
      based HIV-1 vaccine, with or without a DNA primer, provided protection from SHIV
      challenge in a macaque model. Replication-competent Tiantan vaccinia is a
      promising vector and should enable advances in HIV-1 vaccine development.

PMID- 25849829
TI  - Dolutegravir inhibits HIV-1 Env evolution in primary human cells.
AB  - OBJECTIVE: In treatment-naive HIV-positive individuals, the integrase strand
      transfer inhibitor dolutegravir (DTG) has not been associated with emergent drug
      resistance mutations, neither against this drug nor against other antiretroviral
      drugs that were used in combination with it. This is in contrast to all other
      antiretroviral drugs tested so far, including the integrase strand-transfer
      inhibitors raltegravir (RAL) and elvitegravir that can lead to treatment failure
      with the emergence of drug-resistance mutations. DESIGN: These observations
      suggest that DTG may provide an additional protection against resistance compared
      to other drugs by decreasing HIV-1 genetic evolution. METHODS: Here, we tested
      this hypothesis by measuring the genetic and amino-acid diversity of Env/gp160
      from two HIV-1 primary isolates that were grown in the presence of increasing
      concentrations of DTG or RAL over the course of 38-55 weeks. RESULTS: The results
      show that treatment with DTG led to less HIV-1 genetic and amino-acid
      diversification over time, as compared to treatment with RAL or the absence of
      drug. CONCLUSION: These results may help to explain the absence of emergent
      resistance mutations in treatment-naive individuals treated with DTG.

PMID- 25849830
TI  - Human adipose tissue as a reservoir for memory CD4+ T cells and HIV.
AB  - OBJECTIVE: The objective of this study is to determine whether adipose tissue
      functions as a reservoir for HIV-1. DESIGN: We examined memory CD4(+) T cells and
      HIV DNA in adipose tissue-stromal vascular fraction (AT-SVF) of five patients
      [four antiretroviral therapy (ART)-treated and one untreated]. To determine
      whether adipocytes stimulate CD4(+) T cells and regulate HIV production, primary
      human adipose cells were cocultured with HIV-infected CD4(+) T cells. METHODS: AT
      SVF T cells were studied by flow cytometry, and AT-SVF HIV DNA (Gag and Env) was
      examined by nested PCR and sequence analyses. CD4(+) T-cell activation and HIV
      production were measured by flow cytometry and ELISA. RESULTS: AT-SVF CD3(+) T
      cells were activated (>60% CD69(+)) memory CD4(+) and CD8(+) T cells in
      uninfected and HIV-infected persons, but the AT-SVF CD4(+)/CD8(+) ratio was lower
      in HIV patients. HIV DNA (Gag and Env) was detected in AT-SVF of all five
      patients examined by nested PCR, comparably to other tissues [peripheral blood
      mononuclear cell (PBMC), lymph node or thymus]. In coculture experiments,
      adipocytes increased CD4(+) T-cell activation and HIV production approximately
      two to three-fold in synergy with gamma-chain cytokines interleukin (IL)-2, IL7
      or IL15. These effects were mitigated by neutralizing antibodies against IL6 and
      integrin-alpha1beta1. Adipocytes also enhanced T-cell viability. CONCLUSION:
      Adipose tissues of ART-treated patients harbour activated memory CD4(+) T cells
      and HIV DNA. Adipocytes promote CD4(+) T-cell activation and HIV production in
      concert with intrinsic adipose factors. Adipose tissue may be an important
      reservoir for HIV.

PMID- 25849831
TI  - Association of microbial translocation biomarkers with clinical outcome in
      controllers HIV-infected patients.
AB  - BACKGROUND: A proportion of patients who spontaneously control viral load
      (controllers) experienced clinical progression. We hypothesized that microbial
      translocation would independently determine the rate of disease progression in
      controllers. METHODS: sCD14, lipopolysaccharide-binding protein (LBP) and EndoCab
      levels were assessed in 114 antiretroviral-naive patients with CD4(+) T cells
      above 500 cells/MUl (including 63 controllers and 51 noncontrollers). The
      independent predictive value of these markers on time to progression to the
      combined endpoint of AIDS, non-AIDS event, initiation of combination
      antiretroviral therapy (cART) or CD4(+) cell count less than 500 cells/MUl was
      assessed using a Cox regression model. RESULTS: Most of the patients progressed
      to a combined endpoint (60%). Clinical progression in controllers was
      significantly lower than in noncontrollers (P = 0.02). Controllers with lower
      than the median baseline CD4(+) T-cell count and higher than the median baseline
      viral load, sCD14 and EndoCab levels had a worse prognosis (P < 0.0001, P =
      0.007, P = 0.05 and P = 0.012), while noncontrollers with higher than the median
      baseline LBP level also had a worse prognosis (P = 0.019). sCD14 and LBP
      increased and EndoCab decreased over time [from baseline (median values: 1486,
      17604 ng/ml and 68 MMU/ml, respectively, to the date of event or the last
      determination (median values: 1663, 20230 ng/ml and 49 MMU/ml), respectively] in
      controllers (P = 0.04, 0.08 and 0.0006, respectively). CONCLUSION: Microbial
      translocation seems to be an important determinant of clinical progression in HIV
      infected controllers independently of viremia. Measures to improve the intestinal
      mucosa damage or decrease translocation could influence the outcome in these
      patients.

PMID- 25849832
TI  - Incomplete immune reconstitution despite virologic suppression in HIV-1 infected
      children and adolescents.
AB  - OBJECTIVES: Some perinatally infected children do not regain normal CD4(+) T-cell
      counts despite suppression of HIV-1 plasma viremia by antiretroviral therapy
      (ART). The frequency, severity and significance of these discordant treatment
      responses remain unclear. DESIGN: We examined the persistence of CD4(+)
      lymphocytopenia despite virologic suppression in 933 children (>= 5 years of age)
      in the USA, Latin America and the Caribbean. METHODS: CD4(+) T-cell trajectories
      were examined and Kaplan-Meier methods used to estimate median time to CD4(+) T
      cell count at least 500 cells/MUl. RESULTS: After 1 year of virologic
      suppression, most (99%) children achieved a CD4(+) T-cell count of at least 200
      cells/MUl, but CD4(+) T-cell counts remained below 500 cells/MUl after 1 and 2
      years of virologic suppression in 14 and 8% of children, respectively. Median
      times to first CD4(+) T-cell count at least 500 cells/MUl were 1.29, 0.78 and
      0.46 years for children with less than 200, 200-349 and 350-499 cells/MUl at the
      start of virologic suppression. New AIDS-defining events occurred in nine
      children, including four in the first 6 months of virologic suppression. Other
      infectious and HIV-related diagnoses occurred more frequently and across a wide
      range of CD4(+) cell counts. CONCLUSION: ART improved CD4(+) cell counts in most
      children, but the time to CD4(+) cell count of at least 500 cells was highly
      dependent upon baseline immunological status. Some children did not reach a
      CD4(+) T-cell count of 500 cells/MUl despite 2 years of virologic suppression.
      AIDS-defining events occurred in 1% of the population, including children in whom
      virologic suppression and improved CD4(+) T-cell counts were achieved.

PMID- 25849833
TI  - Risk of progression to high-grade anal intraepithelial neoplasia in HIV-infected
      MSM.
AB  - OBJECTIVE: To assess the value of several factors to predict the risk of
      progression to high-grade anal intraepithelial neoplasia (HGAIN) in a cohort of
      HIV-infected MSM. DESIGN: Longitudinal study of 556 HIV-infected MSM who
      underwent screening for anal dysplasia (include anal cytology and high-resolution
      anoscopy at each visit). METHODS: Progression rate to HGAIN was estimated by
      Kaplan-Meier analysis. Predictors of progression were assessed by Cox
      proportional hazards regression. RESULTS: Sixty-eight incidents HGAIN cases over
      649 person-years of follow-up were diagnosed, resulting in a progression rate of
      10.5 cases/100 person-years [95% confidence interval (CI), 8.1-13.3). The
      cumulative incidence of HGAIN was 7.2% at 12 months (95% CI, 4.3-10.1) and 16.2%
      at 24 months (95% CI, 11.7-20.7). Independent risk factors for progression were
      as follows: abnormal cytology [hazard ratio (HR), 2.5 (95% CI, 1.2-4.9) if low
      grade squamous intraepithelial lesion, HR 2.76 (95% CI, 1.4-5.3) if atypical
      squamous cells of uncertain significance and HR 7.73 (95% CI, 2.3-25.4) if high
      grade squamous intraepithelial lesion], abnormal high-resolution anoscopy (HR
      3.57; 95% CI, 2-6.4) and infection by 16 or 18 human papillomavirus (HR 1.63; 95%
      CI, 1-2.6). To be receiving HAART (HR 0.4; 95% CI, 0.2-0.7) and have stable
      sexual couple (HR 0.62; 95% CI, 0.4-0.9) were protective factors. Patients with
      favorable predictors had an incident rate of 2.86 cases/100 person-years (95% CI,
      3.5-10.3). CONCLUSION: The rate of progression to HGAIN varies according to
      different predictors that should be considered when assessing the particular risk
      of each patient. Patients with low risk of progression could be screened at
      longer intervals. BRIEF SUMMARY: We describe the risk of progression to HGAIN in
      a cohort of 556 HIV-infected MSM. The incidence rate of HGAIN varies widely
      according to different predictors. These factors should be considered when
      assessing the particular risk of each patient.

PMID- 25849834
TI  - Effects of HIV and combination antiretroviral therapy on cortico-striatal
      functional connectivity.
AB  - OBJECTIVE: Determine whether HIV and combination antiretroviral therapy (cART)
      affect resting-state functional connectivity (rs-fc) between the striatum and the
      cortical regions. METHODS: Forty-nine HIV-uninfected (HIV-) and 132 HIV-infected
      (HIV+) (65% receiving cART) patients underwent laboratory studies (current and
      nadir CD4 T-cell counts, and plasma HIV viral load), neuropsychological
      performance testing, and neuroimaging. Rs-fc, which examines the coordination of
      neural activity in distant brain regions, was used to investigate the cortico
      striatal functional connections. The effect of cART was assessed comparing HIV+
      individuals on cART (HIV+/cART+), and HIV+ individuals not currently receiving
      cART (HIV+/cART-). Relationships between laboratory tests, cognitive performance,
      and cART on subcortical-cortical rs-fc were assessed by an analysis of variance.
      RESULTS: HIV+ individuals had lower cortico-striatal functional connectivity than
      HIV- controls, specifically between the striatum and the default mode network (P
      < 0.001) and ventral attention network (P < 0.001). HIV+/cART+ individuals had
      higher functional connectivity between the striatum, and default mode network (P
      = 0.02) and ventral attention network (P = 0.01), compared to the HIV+/cART-
      patients. Laboratory (current and nadir CD4 T-cell counts, plasma viral load) and
      neuropsychological performance was not correlated with cortico-striatal rs-fc.
      CONCLUSIONS: HIV was associated with disrupted cortico-striatal networks,
      consistent with HIV's known impact on the subcortical areas. Interestingly,
      within certain networks, HIV+/cART+ individuals had similar rs-fc compared to HIV
      controls, suggesting possible improvements in HIV-related neural dysfunction due
      to medications. Rs-fc may be a sensitive biomarker of neural insult and its
      recovery following cART. Additional studies may show rs-fc has utility in
      measuring acute inflammation caused by HIV.

PMID- 25849836
TI  - Estimating the range of potential epidemiological impact of pre-exposure
      prophylaxis: run-away success or run-away failure?
AB  - OBJECTIVE: To investigate the influence of potential interactions between key
      aspects of a pre-exposure prophylaxis (PrEP) intervention on projections of
      epidemiological impact and cost-effectiveness. METHODS: A mathematical model
      representing the HIV epidemic and intervention context in Nyanza province in
      Kenya was developed. We consider a scenario whereby a fixed annual budget is
      allocated to a PrEP intervention. A standard projection of impact is generated,
      assuming that the unit cost of PrEP, adherence to PrEP and the ability of the
      programme to direct PrEP to those at high risk, all stay constant. The influence
      of dynamic assumptions and possible interactions between PrEP intervention
      assumptions is then assessed in comparison. RESULTS: The cumulative impact of a
      PrEP intervention could be increased approximately two-fold, relative to the
      standard projection, if positive interactions (between coverage and cost,
      coverage and adherence, prioritization and time) are assumed, whereas negative
      interactions between these factors could almost entirely negate the preventive
      benefit of the PrEP intervention. The corresponding estimates of cost per
      infection averted span a wide range from $2060 to $36360. CONCLUSIONS: Multiple
      potentially interacting factors will determine the impact of PrEP. Model
      forecasts should reflect that uncertainty and programmes should focus on these
      factors and measure them, to maximize the impact of programmes.

PMID- 25849835
TI  - High HIV prevalence and incidence among MSM across 12 cities in India.
AB  - OBJECTIVE: To characterize prevalence, incidence, and associated correlates of
      HIV infection among MSM in 12 cities across India. DESIGN: Cross-sectional sample
      using respondent-driven sampling from September 2012 to June 2013. METHODS: A
      total 12022 MSM (~1000/city) were recruited. Participants had to be at least 18
      years, self-identify as male, and report oral/anal intercourse with a man in the
      prior year. HIV infection was diagnosed using three rapid tests. Cross-sectional
      HIV incidence was estimated using a multiassay algorithm. All estimates
      incorporate respondent-driven sampling-II weights. RESULTS: Median age was 25
      years, 45% self-identified as 'panthi' (predominantly penetrative anal
      intercourse) and 30.6% reported being married to a woman. Weighted HIV prevalence
      was 7.0% (range: 1.7-13.1%). In multivariate analysis, significantly higher odds
      of HIV infection was observed among those who were older, had lower educational
      attainment, were practicing purely receptive anal sex or both receptive and
      penetrative sex, and those who were herpes simplex virus-2 positive. Of 1147 MSM
      who tested HIV positive, 53 were identified as recent HIV infections (annualized
      incidence = 0.87%; range = 0-2.2%). In multivariate analysis, injecting drugs in
      the prior 6 months, syphilis, and higher number of male partners and fewer female
      partners were significantly associated with recent HIV infection. CONCLUSION: We
      observed a high burden of HIV among MSM in India with tremendous diversity in
      prevalence, incidence, and risk behaviors. In particular, we observed high
      incidence in areas with relatively low prevalence suggesting emerging epidemics
      in areas not previously recognized to have high HIV burden.

PMID- 25849837
TI  - Human papilloma virus vaccination induces strong human papilloma virus specific
      cell-mediated immune responses in HIV-infected adolescents and young adults.
AB  - The ability of a quadrivalent human papilloma virus (HPV)-16/18/6/11 virus-like
      particles vaccine (Gardasil) to elicit HPV-specific cell-mediated immune
      responses was evaluated in antiretroviral therapy (ART)-treated HIV-infected
      young adults. Results showed that, after three doses of vaccine, central memory
      and effector memory CD4(+) and CD8(+) T lymphocytes, as well as HPV-specific
      interleukin (IL)2(+)/CD4(+), interferon-gamma (IFN-gamma(+))/CD4(+), IFN
      gamma(+)/CD8(+) and tumour necrosis factor-alpha (TNF-alpha)(+)/CD8(+) T
      lymphocytes and Perforin and Granzyme B secreting CD8(+) T lymphocytes were
      significantly increased. Notably, results obtained in HIV-infected patients were
      comparable to those seen in HIV-uninfected age-matched healthy controls.

PMID- 25849838
TI  - Protein-losing enteropathy in an HIV-infected pediatric patient with previous
      disseminated Mycobacterium genavense infection.

PMID- 25849839
TI  - Proximal tubular dysfunction in a HIV-1 patient with coadministered tenofovir
      disoproxil-fumarate and ibuprofen.

PMID- 25849840
TI  - Management guidelines for non-AIDS morbidity result in increased screening but no
      change in primary prevention implementation.

PMID- 25849841
TI  - Response to: The relationship of physical performance with HIV disease and
      mortality: a cohort study.

PMID- 25849842
TI  - The relationship of physical performance with HIV disease and mortality: authors'
      response.

PMID- 25849843
TI  - Retention in care for HIV-infected patients in the eye of the Ebola storm:
      lessons from Monrovia, Liberia.

PMID- 25849844
TI  - Can yeast isolation be predicted in complicated secondary non-postoperative intra
      abdominal infections?
AB  - INTRODUCTION: The aim of this study was to create a predictive score for yeast
      isolation in patients with complicated non-postoperative intra-abdominal
      infections (CNPIAI) and to evaluate the impact of yeast isolation on outcome.
      METHODS: All patients with a CNPIAI undergoing emergency surgery over a three
      year period were included in the retrospective cohort (RC, n = 290). Patients
      with a yeast-positive peritoneal fluid culture (YP) were compared with patients
      with a yeast-negative culture (YN). Multivariate logistic regression was used to
      identify factors independently associated with yeast isolation and a predictive
      score was built. The score's performance was then established in the prospective
      cohort (PC, n = 152) over an 18-month period. Outcome of the whole cohort was
      evaluated and independent risks factors of mortality searched. RESULTS: In the
      RC, 39 patients (13.4%) were YP. Four factors were independently associated with
      the YP group: length of stay before surgery >=48 h (odds ratio (OR) (95%
      confidence interval (CI)) = 3.1 (1.4 to 6.9), P = 0.004, 1 point), per-operative
      cardiovascular failure (2.4 (1.1 to 5.8), P = 0.04, 1 point), generalized
      peritonitis (6.8 (2.7 to 16.7), P <0.001, 2 points) and upper gastrointestinal
      tract perforation (2.5 (1.2 to 5.6), P = 0.02, 1 point). In the PC, the area
      under the curve (95%CI) of the predictive score's receiver operating
      characteristic curve was 0.79 (0.72 to 0.86). For predicting an intra-abdominal
      candidiasis (IAC), a score >=3 had a sensitivity of 0.60, a specificity of 0.84,
      a positive predictive value of 0.49 and a negative predictive value of 0.89.
      Furthermore, yeast isolation was associated with worse outcome and independently
      associated with mortality in the whole cohort (OR = 2.15; 95%CI (1.03 to 4.46), P
      = 0.04). CONCLUSIONS: The new predictive score can be used to rule out intra
      abdominal candidiasis and thus avoid the initiation of antifungal treatment. It
      is suited to less severe infections than previously published scores. IAC is
      associated independently with an increased mortality in this population.

PMID- 25849845
TI  - Effect of arsenite on nitrosative stress in human breast cancer cells and its
      modulation by flavonoids.
AB  - Arsenic (As) is used in the treatment of leukemia and breast cancer due to its
      oxidative cytotoxic action. However, it is also toxic to normal cells. One
      proposed anticancer mechanism induced by As might be nitrosative stress (NS). It
      is believed that antioxidant flavonoids in combination with As might reduce its
      toxic action on normal cells without interfering with its antitumor action. In
      the present study, we evaluated the antineoplastic potential of As on breast
      human cancer lines MCF-7 and ZR-75-1 treated with redox-modulating flavonoids,
      such as quercetin (Q) and silymarin (S). Even though both cell lines differed
      about their oxidative responsiveness, their viability was decreased by NS
      induction through gamma-glutamyltranspeptidase inhibition. Arsenic triggered NS
      in both MCF-7 and ZR-75-1 cultures, with the formers more sensitive without
      recovering their pre-treatment capacity. ZR-75-1 cells maintained their
      antioxidant status, whereas MCF-7 ones treated with S, As, and As + Q did not.
      Silymarin did not interfere with the described As bioactivity. NS was an
      anticancer mechanism exerted by As depending on the redox cellular response that
      could be differentially modified by dietary antioxidants. Hence, it is worthwhile
      to consider the use of dietary antioxidants as adjuvant in cancer chemotherapy,
      especially when using As. 

PMID- 25849846
TI  - Presence of circulating Her2-reactive CD8 + T-cells is associated with lower
      frequencies of myeloid-derived suppressor cells and regulatory T cells, and
      better survival in older breast cancer patients.
AB  - INTRODUCTION: Breast cancer is one of the most common cancers among women. Its
      incidence is increasing in many countries and a higher number of older women are
      now being diagnosed with the disease. Immune parameters are implicated in disease
      progression, and the frequencies of both myeloid-derived suppressor cells (MDSCs)
      and regulatory T cells (Tregs), associated with tumour burden, have been
      suggested to be indicators of poor prognosis in cases of metastatic breast
      cancer. METHODS: Here, we have assessed the frequency of peripheral Tregs and
      MDSCs in relation to in vitro T cell responses to Her2 antigen in 40 untreated
      breast cancer patients 65 to 87 years of age at diagnosis. RESULTS: The five-year
      survival rate of patients who mounted a CD8+ T cell response to Her2 peptides and
      had a lower frequency of Lin-CD14+HLA-DR-MDSCs was 100% compared to only 38% in
      patients without Her2-reactive CD8+ T cells and with higher frequencies of MDSCs
      (P = 0.03). Patients who lacked a CD8 response to Her2 tended to have higher
      frequencies of MDSCs. Similarly, patients who lacked a CD8 response to Her2 and
      had higher frequencies of CD4+Foxp3+CD127lowCD25+ Tregs had only 50% survival
      compared to the 100% survival of patients who did mount a CD8 response and had
      lower frequencies of Tregs (P = 0.03). A similar trend was observed for activated
      (CD4+CD45RA-Foxp3hi) but not resting Tregs (CD4+CD45RA+FoxP3+). This survival
      advantage was observed in both metastatic and non-metastatic patients.
      CONCLUSIONS: Our data demonstrate a negative role of both MDSCs and Tregs in the
      prognosis of breast cancer patients, the mechanism of which might be through
      dampening favourable CD8+ T cell immune responses to tumour-associated antigens.

PMID- 25849847
TI  - Parent-reported symptoms of acute otitis media during the first year of life:
      what is beneath the surface?
AB  - BACKGROUND: Most estimates of the incidence of acute otitis media (AOM) are based
      on general practitioner (GP) or pediatrician diagnoses. It is likely that these
      figures underestimate the community incidence of AOM since parents do not visit
      their doctor every time their child suffers from acute ear symptoms. The impact
      of these symptom episodes may be substantial since they affect the child's
      quality of life and parents' productivity. METHODS: To determine AOM symptoms in
      the community, we measured parent-reported AOM symptoms daily for 12 consecutive
      months in 1,260 children participating in a prospective birth cohort in the
      Netherlands. The mean age of these children was at study enrollment 0.9 months
      (standard deviation 0.6). A parent-reported AOM symptom episode was defined as
      fever (temperature 38C or above) plus at least one of the following symptoms: ear
      pain and ear discharge. These febrile AOM symptom episodes were linked to GP
      consultations and diagnoses in the GP electronic health records. RESULTS: With an
      estimated 624 parent-reported symptom episodes per 1,000 child-years (95% CI: 577
      to 674) incidence of febrile AOM symptoms during the child's first year is high.
      The GP was consulted in half of these symptom episodes and AOM was diagnosed in
      49% of these consultations. CONCLUSIONS AND RELEVANCE: The incidence of febrile
      AOM symptoms in the first year of life is high in Dutch children and leads to a
      GP-consultation in only half of the cases. This suggests that AOM symptomatology
      in the community is underestimated when focusing on GP-diagnosed AOM episodes
      alone, since a considerable proportion of febrile AOM symptom episodes are
      treated symptomatically by parents at home and do not come to the attention of
      the GP. Having data on community AOM symptomatology available for each country is
      important when the potential impact of preventive and therapeutic interventions
      for AOM are studied.

PMID- 25849848
TI  - Iron(III) complexes of a pyridoxal Schiff base for enhanced cellular uptake with
      selectivity and remarkable photocytotoxicity.
AB  - Iron(III) complexes of pyridoxal (vitamin B6, VB6) or salicylaldehyde Schiff
      bases and modified dipicolylamines, namely, [Fe(B)(L)](NO3) (1-5), where B is
      phenyl-N,N-bis((pyridin-2-yl)methyl)methanamine (phbpa in 1), (anthracen-9-yl)
      N,N-bis((pyridin-2-yl)methyl)methanamine (anbpa in 2, 4) and (pyren-1-yl)-N,N
      bis((pyridin-2-yl)methyl)methanamine (pybpa in 3, 5) (H2L(1) is 3-hydroxy-5
      (hydroxymethyl)-4-(((2-hydroxyphenyl)imino)methyl)-2-methylpyridine (1-3) and
      H2L(2) is 2-[(2-hydroxyphenyl-imino)methyl]phenol), were prepared and their
      uptake in cancer cells and photocytotoxicity were studied. Complexes 4 and 5,
      having a non-pyridoxal Schiff base, were prepared to probe the role of the
      pyridoxal group in tumor targeting and cellular uptake. The PF6 salt (1a) of
      complex 1 is structurally characterized. The complexes have a distorted six
      coordinate FeN4O2 core where the metal is in the +3 oxidation state with five
      unpaired electrons. The complexes display a ligand to metal charge transfer band
      near 520 and 420 nm from phenolate to the iron(III) center. The photophysical
      properties of the complexes are explained from the time dependent density
      functional theory calculations. The redox active complexes show a quasi
      reversible Fe(III)/Fe(II) response near -0.3 V vs saturated calomel electrode.
      Complexes 2 and 3 exhibit remarkable photocytotoxicity in various cancer cells
      with IC50 values ranging from 0.4 to 5 MUM with 10-fold lower dark toxicity. The
      cell death proceeded by the apoptotic pathway due to generation of reactive
      oxygen species upon light exposure. The nonvitamin complexes 4 and 5 display 3
      fold lower photocytotoxicity compared to their VB6 analogues, possibly due to
      preferential and faster uptake of the vitamin complexes in the cancer cells.
      Complexes 2 and 3 show significant uptake in the endoplasmic reticulum, while
      complexes 4 and 5 are distributed throughout the cells without any specific
      localization pattern. 

PMID- 25849849
TI  - Patterned Carboxylation of Graphene Using Scanning Electrochemical Microscopy.
AB  - A simple, direct, and versatile scanning electrochemical microscopy (SECM)
      approach for local carboxylation of multilayered graphene on nickel is
      demonstrated, in which carbon dioxide serves as the carboxylation agent under
      reductive conditions in N,N-dimethylformamide. The use of SECM gives control over
      both the spatial dimensions and the degree of carboxylation. While the pattern
      size, in general, is governed by the dimension of the SECM tip, the degree of
      modification, expressed as the surface coverage of carboxylate groups introduced
      at the graphene substrate, is found to be controlled by the electrolysis time.
      This is supported by electrochemical measurements, two-dimensional X-ray
      photoelectron spectroscopy, Raman spectroscopy mapping, and He ion microscopy.
      Surprisingly, intercalation of the supporting electrolyte in the multilayered
      graphene on nickel occurs to a relatively small extent when compared to
      corresponding results obtained in previously described carboxylations of this
      kind of multilayered graphene. 

PMID- 25849850
TI  - Rapid decrease in salivary epidermal growth factor levels in patients with
      Sjogren's syndrome: A 3-year follow-up study.
AB  - OBJECTIVES: To assess changes in salivary epidermal growth factor (EGF) levels
      within three years and investigate the correlation between these changes and the
      severity of intraoral manifestations in patients with Sjogren's syndrome (SS).
      METHODS: Twenty-three SS patients (14 primary SS and 9 secondary SS) and 14
      controls were followed up for three years. Salivary EGF concentration was
      measured using an enzyme-linked immunosorbent assay, and intraoral manifestations
      were evaluated using a short version of the Oral Health Impact Profile (OHIP-14).
      Changes in salivary flow rate, EGF level, and severity of intraoral
      manifestations were analyzed, along with associations among them. RESULTS: The
      OHIP-14 score significantly increased and the total salivary EGF output
      significantly decreased after three years in the SS group (10.2 +/- 8.8 vs. 12.6
      +/- 9.2, p = 0.040; 10158.4 +/- 9820.9 vs. 8352.8 +/- 7813.3 pg/10 min, p =
      0.032), though the salivary flow rate did not change. The decrease in total EGF
      output was especially high in patients with long disease duration and poor oral
      health-related quality of life (OHRQoL). In patients with poor OHRQoL, the change
      in total EGF output significantly correlated with the OHIP-14 score (r = - 0.847,
      p = 0.008). However, there was no correlation between the change in salivary flow
      rate and the OHIP-14 score. CONCLUSIONS: The rapid decrease in salivary EGF level
      contributes to the progression of intraoral manifestations of SS.

PMID- 25849851
TI  - Utility of ferritin as a predictor of the patients with Kawasaki disease
      refractory to intravenous immunoglobulin therapy.
AB  - OBJECTIVES: The aim of this study is to investigate whether ferritin can be a
      useful marker for the prediction of the patients with Kawasaki disease (KD)
      refractory to initial intravenous immunoglobulin (IVIG) therapy. METHODS: This
      retrospective study enrolled 85 patients with KD hospitalized at Kitakyushu
      General Hospital during 2010-2014. These patients were divided into IVIG
      responders (n = 57) and non-responders (n = 28). Serum ferritin levels and the
      scoring systems for the prediction of non-responsiveness to initial IVIG therapy
      were compared between these two groups. RESULTS: Serum ferritin level was
      significantly elevated in non-responders (p = 0.010). The area under the receiver
      operating characteristics curve was 0.674, and the sensitivity and specificity in
      more than 165 ng/ml of serum ferritin level were 70.4% and 63.2%, respectively.
      In two of the three prediction scoring systems, non-responders also showed
      significantly higher scores than responders, but many non-responders had low
      scores of these scoring systems. More than half of the patients with a low score
      of these scoring systems had high serum ferritin level (>= 165 ng/ml).
      CONCLUSIONS: Serum ferritin level might be a useful marker for the prediction of
      non-responsiveness to initial IVIG therapy and could be an important
      complementary marker to the prediction scoring systems.

PMID- 25849852
TI  - Systemic sclerosis and risk of venous thromboembolism: A systematic review and
      meta-analysis.
AB  - BACKGROUND: Several chronic inflammatory disorders, such as rheumatoid arthritis,
      inflammatory myositis, and systemic vasculitides, have been linked to an
      increased risk of venous thromboembolism (VTE). However, the data on systemic
      sclerosis (SSc) remains unclear. METHODS: We conducted a systematic review and
      meta-analysis of observational studies that reported odds ratio, relative risk,
      hazard ratio, or standardized incidence ratio comparing risk of VTE in patients
      with SSc versus non-SSc participants. Pooled risk ratio and 95% confidence
      intervals (CIs) were calculated using a random-effect, generic inverse variance
      method of DerSimonian and Laird. RESULTS: Out of 776 potentially relevant
      articles, five eligible studies were identified and included in the data
      analysis. The pooled risk ratio of VTE in patients with SSc was 2.51 (95% CI,
      1.79-3.54). The statistical heterogeneity of this study was high with an I2 of
      90%. CONCLUSIONS: Our study demonstrated a statistically significant increased
      VTE risk among patients with SSc.

PMID- 25849853
TI  - The effect of isokinetic and aerobic exercises on serum interleukin-6 and tumor
      necrosis factor alpha levels, pain, and functional activity in patients with knee
      osteoarthritis.
AB  - OBJECTIVES: The aim of this study is to investigate the effects of isokinetic and
      aerobic exercise training programs on serum pro-inflammatory cytokine levels,
      pain, and functional activity in patients with knee osteoarthritis (OA). METHODS:
      Forty-two postmenopausal women and men with knee OA according to American College
      of Rheumatology diagnostic criteria were included. Patients were randomized into
      isokinetic and aerobic exercises and control groups. In intervention groups,
      patients were included in predetermined exercise programs 3 times per week for 6
      weeks. Severity of pain, functional activity status, muscle strength, functional
      capacity, and serum cytokine levels were evaluated at baseline and at the 6th
      week. RESULTS: At the end of 6th week, there was no statistically significant
      decrease in serum pro-inflammatory cytokine levels in both the exercise groups,
      although C-reactive protein levels exhibited a strong trend toward significance.
      We found a significant decrease in visual analog scale and Western Ontario
      McMaster Osteoarthritis Index scores, and significant increase in functional
      capacity and muscle strength in both the exercise groups compared with those in
      the control group.

PMID- 25849854
TI  - TAp63gamma and DeltaNp63beta promote osteoblastic differentiation of human
      mesenchymal stem cells: regulation by vitamin D3 Metabolites.
AB  - The transcription factor p63 is required for skeletal formation, and is important
      for the regulation of 1alpha,25(OH)2D3 receptor (VDR) in human mesenchymal stem
      cells (hMSC). Herein we report that TAp63gamma and DeltaNp63beta appear to be an
      integral part of the osteoblastic differentiation of hMSC and are differentially
      regulated by the vitamin D3 metabolites 1alpha,25(OH)2D3 and 24R,25(OH)2D3. We
      compared the endogenous expression of p63 isoforms (TA- and DeltaNp63) and splice
      variants (p63alpha, -beta, -gamma), in naive hMSC and during osteoblastic
      differentiation of hMSC. TAp63alpha and -beta were the predominant p63 variants
      in naive, proliferating hMSC. In contrast, under osteoblastic differentiation
      conditions, expression of p63 changed from the TAp63alpha and -beta to the
      TAp63gamma and DeltaNp63beta variants. Transient overexpression of the p63
      variants demonstrated that TAp63beta, DeltaNp63beta, and DeltaNp63gamma increased
      alkaline phosphatase activity and DeltaNp63alpha and -gamma increased the
      expression of mRNA for osteocalcin and osterix. Our results support the
      hypothesis that TAp63alpha and -beta promote a naive state in hMSC. Moreover,
      TAp63gamma is increased during and promotes early osteoblastic differentiation
      through the expression of pro-osteogenic genes; VDR, Osterix, Runx2 and
      Osteopontin. DeltaNp63beta also appears to support osteogenic maturation through
      increased alkaline phosphatase activity. Treatment with 1alpha,25(OH)2D3
      increased the expression of mRNA for DeltaNp63, while addition of 24R,25(OH)2D3
      increased the expression of TA- and DeltaNp63gamma variants. These novel findings
      demonstrate for the first time that p63 variants are differentially expressed in
      naive hMSC (TAp63alpha,beta), are important during the osteoblastic
      differentiation of hMSC (TAp63gamma and DeltaNp63beta), and are differentially
      regulated by the vitamin D3 metabolites, 1alpha,25(OH)2D3 and 24R,25(OH)2D3. The
      molecular nuances and mechanisms of osteoblastic differentiation presented here
      will hopefully improve our understanding of bone development, complications in
      bone repair (mal- and non-union fractures), osteoporosis and possibly lead to new
      modalities of treatment. 

PMID- 25849855
TI  - Multi-locus analysis of genomic time series data from experimental evolution.
AB  - Genomic time series data generated by evolve-and-resequence (E&R) experiments
      offer a powerful window into the mechanisms that drive evolution. However,
      standard population genetic inference procedures do not account for sampling
      serially over time, and new methods are needed to make full use of modern
      experimental evolution data. To address this problem, we develop a Gaussian
      process approximation to the multi-locus Wright-Fisher process with selection
      over a time course of tens of generations. The mean and covariance structure of
      the Gaussian process are obtained by computing the corresponding moments in
      discrete-time Wright-Fisher models conditioned on the presence of a linked
      selected site. This enables our method to account for the effects of linkage and
      selection, both along the genome and across sampled time points, in an
      approximate but principled manner. We first use simulated data to demonstrate the
      power of our method to correctly detect, locate and estimate the fitness of a
      selected allele from among several linked sites. We study how this power changes
      for different values of selection strength, initial haplotypic diversity,
      population size, sampling frequency, experimental duration, number of replicates,
      and sequencing coverage depth. In addition to providing quantitative estimates of
      selection parameters from experimental evolution data, our model can be used by
      practitioners to design E&R experiments with requisite power. We also explore how
      our likelihood-based approach can be used to infer other model parameters,
      including effective population size and recombination rate. Then, we apply our
      method to analyze genome-wide data from a real E&R experiment designed to study
      the adaptation of D. melanogaster to a new laboratory environment with
      alternating cold and hot temperatures. 

PMID- 25849856
TI  - Lung function, symptoms and inflammation during exacerbations of non-cystic
      fibrosis bronchiectasis: a prospective observational cohort study.
AB  - BACKGROUND: Exacerbations of non-cystic fibrosis bronchiectasis cause significant
      morbidity but there are few detailed data on their clinical course and associated
      physiological changes. The biology of an exacerbation has not been previously
      described. METHODS: This was a prospective observational cohort study of 32
      outpatients with non-cystic fibrosis bronchiectasis conducted between August 2010
      and August 2012. Patients completed a symptom diary card and measured their peak
      expiratory flow rate (PEFR) daily. Exacerbations were defined as oral antibiotic
      treatment taken for a worsening of respiratory symptoms. Symptoms and peak flow
      at exacerbation were analysed, and further measurements including the COPD
      Assessment Test (CAT) and inflammatory markers were also compared to baseline
      values. RESULTS: At baseline, health status was significantly related to lung
      function, prognostic severity and systemic inflammation. 51 exacerbations
      occurred in 22 patients. Exacerbation symptoms began a median (interquartile
      range) of 4 (2, 7) days before treatment started and the median exacerbation
      duration was 16 (10, 29) days. 16% had not recovered by 35 days. At exacerbation,
      mean PEFR dropped by 10.6% (95% confidence interval 6.9-14.2, p < 0.001) and mean
      CAT score increased by 6.3 units (3.6-9.1, p = 0.001), median symptom count by 4
      (2.25, 6, p < 0.001), and mean CRP by 9.0mg/L (2.3-15.8, p = 0.011).
      Exacerbations where PEFR fell by >=10% were longer with more symptoms at onset.
      CONCLUSION: Exacerbations of non-CF bronchiectasis are inflammatory events, with
      worsened symptoms, lung function and health status, and a prolonged recovery
      period. Symptom diary cards, PEFR and CAT scores are responsive to changes at
      exacerbation and may be useful tools for their detection and monitoring.

PMID- 25849857
TI  - Biosensor enhancement using grooved micromixers: part I, numerical studies.
AB  - In this study we examine the use of the staggered herringbone mixer (SHM) to
      increase the efficiency of analyte delivery to a planar biosensor surface.
      Although there has been an extensive amount of research regarding the
      optimization of the SHM for mixing purposes, there has been very little work
      regarding the use of said micromixers for sensing purposes. Here, we use
      numerical methods to examine the effect of the SHM geometry on the efficiency of
      analyte delivery to a biosensor surface. We show the level of sensing enhancement
      of an SHM-based sensing chamber over that of an unmixed chamber has a strong
      dependence on the SHM geometry, the Peclet number, and the overall sensor length.
      The results presented herein are applicable to a very wide range of biosensor
      transduction mechanisms and target analytes. 

PMID- 25849858
TI  - Contemporary Trends in the Ambulatory Surgical Treatment of Urolithiasis:
      Population-Based Analysis.
AB  - PURPOSE: To describe the utilization of shockwave lithotripsy (SWL) and
      ureteroscopy (URS) in ambulatory surgery centers, as well as to identify patient
      specific factors predictive of one procedure over the other. PATIENTS AND
      METHODS: We evaluated the current trends in the use of SWL and URS in the
      ambulatory settings over a 5-year period in the state of California using the
      State of California Office of Statewide Health Planning and Development (OSHPD)
      database. RESULTS: We identified 113,447 ambulatory kidney stone surgical
      procedures including 64,632 SWL (57%) and 48,815 URS (43%) treatments in the
      OSHPD database between 2005 and 2010. The total annual ambulatory stone surgeries
      increased from 17,831 cases in 2005 to 18,933 cases in 2010 (P<0.001). Between
      2005 and 2010, the use of URS increased significantly from 6978 (39%) cases in
      2005 to 9259 (49%) cases in 2010 (P<0.0012), whereas the use of SWL decreased
      from 10,853 (61%) cases in 2005 to 9674 (51%) cases in 2010 (P=0.0012). In
      multivariate analysis, age >= 75 years (P<0.001), hypertension (P=0.025), and
      obesity (P<0.001) all increased odds of undergoing URS. In addition, men
      (P=0.013) and non-Medicaid patients (P<0.001) were more likely to undergo URS.
      CONCLUSIONS: The use of URS increased significantly in the state of California
      among patients undergoing urinary stone surgical procedures in the ambulatory
      setting, while the use of SWL decreased between 2005 and 2010. Possible
      explanations for these trends include improved URS stone-free rates, improved
      cost-effectiveness of URS, and enhanced technology leading to increased use of
      URS over SWL.

PMID- 25849859
TI  - The anxiolytic effect of midazolam in third molar extraction: a systematic
      review.
AB  - PURPOSE: To assess the efficacy of midazolam for anxiety control in third molar
      extraction surgery. METHODS: Electronic retrievals were conducted in Medline (via
      PubMed, 1950-2013.12), the Cochrane Central Register of Controlled Trials
      (CENTRAL) (The Cochrane Library 2013, Issue 3), Embase (via OVID 1974-2013.12),
      and the System for Information on Grey Literature in Europe (SIGLE). The
      bibliographies of relevant clinical trials were also checked. Randomized
      controlled trials satisfying the inclusion criteria were evaluated, with data
      extraction done independently by two well-trained investigators. Disagreements
      were resolved by discussion or by consultation with a third member of the review
      team. RESULTS: Ten studies were included, but meta-analysis could not be
      conducted because of the significant differences among articles. All but one
      article demonstrated that midazolam could relieve anxiety. One article
      demonstrated that propofol offered superior anxiolysis, with more rapid recovery
      than with midazolam. Compared with lorazepam and diazepam, midazolam did not
      distinctly dominate in its sedative effect, but was safer. Two articles used
      midazolam in multidrug intravenous sedation and proved it to be more effective
      than midazolam alone. CONCLUSION: It was found, by comparison and analysis, that
      midazolam might be effective for use for anxiety control during third molar
      extraction and can be safely administered by a dedicated staff member. It can
      also be used with other drugs to obtain better sedative effects, but the
      patient's respiratory function must be monitored closely, because multidrug
      sedation is also more risky.

PMID- 25849861
TI  - Methadone for Pain: What to Do When the Oral Route Is Not Available.

PMID- 25849863
TI  - Correction: High rates of o'nyong nyong and Chikungunya virus transmission in
      coastal Kenya.

PMID- 25849862
TI  - Mitogen-activated protein kinases are associated with the regulation of
      physiological traits and virulence in Fusarium oxysporum f. sp. cubense.
AB  - Fusarium oxysporum f. sp. cubense (FOC) is an important soil-borne fungal
      pathogen causing devastating vascular wilt disease of banana plants and has
      become a great concern threatening banana production worldwide. However, little
      information is known about the molecular mechanisms that govern the expression of
      virulence determinants of this important fungal pathogen. In this study, we
      showed that null mutation of three mitogen-activated protein (MAP) kinase genes,
      designated as FoSlt2, FoMkk2 and FoBck1, respectively, led to substantial
      attenuation in fungal virulence on banana plants. Transcriptional analysis
      revealed that the MAP kinase signaling pathway plays a key role in regulation of
      the genes encoding production of chitin, peroxidase, beauvericin and fusaric
      acid. Biochemical analysis further confirmed the essential role of MAP kinases in
      modulating the production of fusaric acid, which was a crucial phytotoxin in
      accelerating development of Fusarium wilt symptoms in banana plants.
      Additionally, we found that the MAP kinase FoSlt2 was required for siderophore
      biosynthesis under iron-depletion conditions. Moreover, disruption of the MAP
      kinase genes resulted in abnormal hypha and increased sensitivity to Congo Red,
      Calcofluor White and H2O2. Taken together, these results depict the critical
      roles of MAP kinases in regulation of FOC physiology and virulence. 

PMID- 25849864
TI  - Significance of microbial asynchronous anabolism to soil carbon dynamics driven
      by litter inputs.
AB  - Soil organic carbon (SOC) plays an important role in the global carbon cycle.
      However, it remains largely unknown how plant litter inputs impact magnitude,
      composition and source configuration of the SOC stocks over long term through
      microbial catabolism and anabolism, mostly due to uncoupled research on litter
      decomposition and SOC formation. This limits our ability to predict soil system
      responses to changes in land-use and climate. Here, we examine how microbes act
      as a valve controlling carbon sequestrated from plant litters versus released to
      the atmosphere in natural ecosystems amended with plant litters varying in
      quantity and quality. We find that litter quality - not quantity - regulates long
      term SOC dynamics under different plausible scenarios. Long-term changes in bulk
      SOC stock occur only when the quality of carbon inputs causes asynchronous change
      in a microbial physiological trait, defined as "microbial biosynthesis
      acceleration" (MBA). This is the first theoretical demonstration that the
      response of the SOC stocks to litter inputs is critically determined by the
      microbial physiology. Our work suggests that total SOC at an equilibrium state
      may be an intrinsic property of a given ecosystem, which ultimately is controlled
      by the asynchronous MBA between microbial functional groups. 

PMID- 25849865
TI  - Actin remodelling factors control ciliogenesis by regulating YAP/TAZ activity and
      vesicle trafficking.
AB  - Primary cilia exert a profound impact on cell signalling and cell cycle
      progression. Recently, actin cytoskeleton destabilization has been recognized as
      a dominant inducer of ciliogenesis, but the exact mechanisms regulating
      ciliogenesis remain poorly understood. Here we show that the actin cytoskeleton
      remodelling controls ciliogenesis by regulating transcriptional coactivator
      YAP/TAZ as well as ciliary vesicle trafficking. Cytoplasmic retention of YAP/TAZ
      correlates with active ciliogenesis either in spatially confined cells or in
      cells treated with an actin filament destabilizer. Moreover, knockdown of YAP/TAZ
      is sufficient to induce ciliogenesis, whereas YAP/TAZ hyperactivation suppresses
      serum starvation-mediated ciliogenesis. We also identify actin remodelling
      factors LIMK2 and TESK1 as key players in the ciliogenesis control network in
      which YAP/TAZ and directional vesicle trafficking are integral components. Our
      work provides new insights for understanding the link between actin dynamics and
      ciliogenesis. 

PMID- 25849866
TI  - Low-temperature growth of bismuth thin films with (111) facet on highly oriented
      pyrolytic graphite.
AB  - The epitaxial growth of artificial two-dimensional metals at interfaces plays a
      key role in fabricating heterostructures for nanoelectronics. Here, we present
      the growth of bismuth nanostructures on highly oriented pyrolytic graphite (HOPG)
      under ultrahigh vacuum (UHV) conditions, which was investigated thoroughly by a
      combination of scanning tunneling microscopy (STM), ultraviolet photoemission
      spectroscopy (UPS), X-ray photoelectron spectroscopy (XPS), and low energy
      electron diffraction (LEED). It was found that (111)-oriented bilayers are formed
      on as-cleaved high-quality HOPG at 140 K, which opens the possibility of making
      Bi(111) thin films on a semimetal, and this is a notable step forward from the
      earlier studies, which show that only Bi(110) facets could be formed at ultrathin
      thickness at room temperature. XPS investigation of both C 1s and Bi 4f reflects
      the rather weak bonding between the Bi film and the HOPG substrate and suggests a
      quasi layer-by-layer growth mode of Bi nanostructures on HOPG at low temperature.
      Moreover, the evolution of the valence band of the interface is recorded by UPS,
      and a transition from quantum well states to bulk-like features is observed at
      varying film thickness. Unlike semimetallic bulk bismuth, ultrathin Bi(111) films
      are expected to be topological insulators. Our study may therefore pave the way
      for the generation of high quality Bi nanostructures to be used in spin
      electronics. 

PMID- 25849868
TI  - A phosphatidylinositol-4-phosphate powered exchange mechanism to create a lipid
      gradient between membranes.
AB  - Lipids are unevenly distributed within eukaryotic cells, thus defining organelle
      identity. How non-vesicular transport mechanisms generate these lipid gradients
      between membranes remains a central question. Here using quantitative, real-time
      lipid transport assays, we demonstrate that Osh4p, a sterol/phosphatidylinositol
      4-phosphate (PI(4)P) exchanger of the ORP/Osh family, transports sterol against
      its gradient between two membranes by dissipating the energy of a PI(4)P
      gradient. Sterol transport is sustained through the maintenance of this PI(4)P
      gradient by the PI(4)P-phosphatase Sac1p. Differences in lipid packing between
      membranes can stabilize sterol gradients generated by Osh4p and modulate its
      lipid exchange capacity. The ability of Osh4p to recognize sterol and PI(4)P via
      distinct modalities and the dynamics of its N-terminal lid govern its activity.
      We thus demonstrate that an intracellular lipid transfer protein actively
      functions to create a lipid gradient between membranes. 

PMID- 25849867
TI  - Oxidation by neutrophils-derived HOCl increases immunogenicity of proteins by
      converting them into ligands of several endocytic receptors involved in antigen
      uptake by dendritic cells and macrophages.
AB  - The initiation of adaptive immune responses to protein antigens has to be
      preceded by their uptake by antigen presenting cells and intracellular
      proteolytic processing. Paradoxically, endocytic receptors involved in antigen
      uptake do not bind the majority of proteins, which may be the main reason why
      purified proteins stimulate at most weak immune responses. A shared feature of
      different types of adjuvants, capable of boosting immunogenicity of protein
      vaccines, is their ability to induce acute inflammation, characterized by early
      influx of activated neutrophils. Neutrophils are also rapidly recruited to sites
      of tissue injury or infection. These cells are the source of potent oxidants,
      including hypochlorous acid (HOCl), causing oxidation of proteins present in
      inflammatory foci. We demonstrate that oxidation of proteins by endogenous,
      neutrophils-derived HOCl increases their immunogenicity. Upon oxidation,
      different, randomly chosen simple proteins (yeast alcohol dehydrogenase, human
      and bovine serum albumin) and glycoproteins (human apo-transferrin, ovalbumin)
      gain the ability to bind with high affinity to several endocytic receptors on
      antigen presenting cells, which seems to be the major mechanism of their
      increased immunogenicity. The mannose receptor (CD206), scavenger receptors A
      (CD204) and CD36 were responsible for the uptake and presentation of HOCl
      modified proteins by murine dendritic cells and macrophages. Other scavenger
      receptors, SREC-I and LOX-1, as well as RAGE were also able to bind HOCl-modified
      proteins, but they did not contribute significantly to these ligands uptake by
      dendritic cells because they were either not expressed or exhibited preference
      for more heavily oxidised proteins. Our results indicate that oxidation by
      neutrophils-derived HOCl may be a physiological mechanism of conferring
      immunogenicity on proteins which in their native forms do not bind to endocytic
      receptors. This mechanism might enable the immune system to detect infections
      caused by pathogens not recognized by pattern recognition receptors. 

PMID- 25849869
TI  - Altered Clathrin-Independent Endocytosis in Type A Niemann-Pick Disease Cells and
      Rescue by ICAM-1-Targeted Enzyme Delivery.
AB  - Pharmaceutical intervention often requires therapeutics and/or their carriers to
      enter cells via endocytosis. Therefore, endocytic aberrancies resulting from
      disease represent a key, yet often overlooked, parameter in designing therapeutic
      strategies. In the case of lysosomal storage diseases (LSDs), characterized by
      lysosomal accumulation of undegraded substances, common clinical interventions
      rely on endocytosis of recombinant enzymes. However, the lysosomal defect in
      these diseases can affect endocytosis, as we recently demonstrated for clathrin
      mediated uptake in patient fibroblasts with type A Niemann-Pick disease (NPD), a
      disorder characterized by acid sphingomylinase (ASM) deficiency and subsequent
      sphingomyelin storage. Using similar cells, we have examined if this is also the
      case for clathrin-independent pathways, including caveolae-mediated endocytosis
      and macropinocytosis. We observed impaired caveolin-1 enrichment at ligand
      binding sites in NPD relative to wild type fibroblasts, corresponding with
      altered uptake of ligands and fluid-phase markers by both pathways. Similarly,
      aberrant lysosomal storage of sphingomyelin induced by pharmacological means also
      diminished uptake. Partial degradation of the lysosomal storage by untargeted
      recombinant ASM led to partial uptake enhancement, whereas both parameters were
      restored to wild type levels by ASM delivery using model polymer nanocarriers
      specifically targeted to intercellular adhesion molecule-1. Carriers also
      restored caveolin-1 enrichment at ligand-binding sites and uptake through the
      caveolar and macropinocytic routes. These results demonstrate a link between
      lysosomal storage in NPD and alterations in clathrin-independent endocytosis,
      which could apply to other LSDs. Hence, this study shall guide the design of
      therapeutic approaches using viable endocytic pathways. 

PMID- 25849870
TI  - Perhexiline promotes HER3 ablation through receptor internalization and inhibits
      tumor growth.
AB  - INTRODUCTION: Human epidermal growth factor receptor HER3 has been implicated in
      promoting the aggressiveness and metastatic potential of breast cancer.
      Upregulation of HER3 has been found to be a major mechanism underlying drug
      resistance to EGFR and HER2 tyrosine kinase inhibitors and to endocrine therapy
      in the treatment of breast cancer. Thus, agents that reduce HER3 expression at
      the plasma membrane may synergize with current therapies and offer a novel
      therapeutic strategy to improve treatment. METHODS: We devised an image-based
      screening platform using membrane localized HER3-YFP to identify small molecules
      that promote HER3 internalization and degradation. In vitro and in vivo tumor
      models were used to characterize the signaling effects of perhexiline, an anti
      anginal drug, identified by the screening platform. RESULTS: We found
      perhexiline, an anti-anginal drug, selectively internalized HER3, decreased HER3
      expression, and subsequently inhibited signaling downstream of HER3. Consistent
      with these results, perhexiline inhibited breast cancer cell proliferation in
      vitro and tumor growth in vivo. CONCLUSIONS: This is the first demonstration that
      HER3 can be targeted with small molecules by eliminating it from the cell
      membrane. The novel approach used here led to the discovery that perhexiline
      ablates HER3 expression, and offers an opportunity to identify HER3 ablation
      modulators as innovative therapeutics to improve survival in breast cancer
      patients.

PMID- 25849871
TI  - Principles and limitations of stable isotopes in differentiating organic and
      conventional foodstuffs: 2. Animal products.
AB  - In this review, we examine the variation in stable isotope signatures of the
      lighter elements (delta2H, delta13C, delta15N, delta18O, and delta34S) of tissues
      and excreta of domesticated animals, the factors affecting the isotopic
      composition of animal tissues, and whether stable isotopes may be used to
      differentiate organic and conventional modes of animal husbandry. The main
      factors affecting the delta13C signatures of livestock are the C3/C4 composition
      of the diet, the relative digestibility of the diet components, metabolic
      turnover, tissue and compound specificity, growth rate, and animal age. delta15N
      signatures of sheep and cattle products have been related mainly to diet
      signatures, which are quite variable among farms and between years. Although few
      data exist, a minor influence in delta15N signatures of animal products was
      attributed to N losses at the farm level, whereas stocking rate showed divergent
      findings. Correlations between mode of production and delta2H and delta18O have
      not been established, and only in one case of an animal product was delta34S a
      satisfactory marker for mode of production. While many data exist on diet-tissue
      isotopic discrimination values among domesticated animals, there is a paucity of
      data that allow a direct and statistically verifiable comparison of the
      differences in the isotopic signatures of organically and conventionally grown
      animal products. The few comparisons are confined to beef, milk, and egg yolk,
      with no data for swine or lamb products. delta13C appears to be the most
      promising isotopic marker to differentiate organic and conventional production
      systems when maize (C4) is present in the conventional animal diet. However,
      delta13C may be unsuitable under tropical conditions, where C4 grasses are
      abundant, and where grass-based husbandry is predominant in both conventional and
      organic systems. Presently, there is no universal analytical method that can be
      applied to differentiate organic and conventional animal products.

PMID- 25849872
TI  - Catalytic chemical amide synthesis at room temperature: one more step toward
      peptide synthesis.
AB  - An efficient method has been developed for direct amide bond synthesis between
      carboxylic acids and amines via (2-(thiophen-2-ylmethyl)phenyl)boronic acid as a
      highly active bench-stable catalyst. This catalyst was found to be very effective
      at room temperature for a large range of substrates with slightly higher
      temperatures required for challenging ones. This methodology can be applied to
      aliphatic, alpha-hydroxyl, aromatic, and heteroaromatic acids as well as primary,
      secondary, heterocyclic, and even functionalized amines. Notably, N-Boc-protected
      amino acids were successfully coupled in good yields with very little
      racemization. An example of catalytic dipeptide synthesis is reported. 

PMID- 25849874
TI  - Collaboration in the new millennium.
AB  - The presidential addresses of the Society for Psychotherapy Research (SPR) of the
      past decade convey a consistency of format and themes. They highlight significant
      weaknesses in some of the basic questions and methodologies of psychotherapy
      researchers. These include neglect of topics concerning the understanding of
      change and over-valuation of the randomized clinical trial (RCT). Although valid,
      the criticisms neglect the strengths of RCTs, which are illustrated by a series
      of psychotherapy clinical trials conducted by the author's research team, and run
      the risk of polarizing psychotherapy researchers. The new millennium is an
      appropriate time to acknowledge how different methodologies complement each other
      and advance knowledge in ways that could not occur in the absence of others. SPR
      is an international, multidisciplinary scientific organization that emphasizes
      inclusiveness. Nevertheless, it, as well as other organizations, can further
      enhance its contribution to the field by extending its range of collaboration to
      include underrepresented researchers, disciplines, and research-oriented
      clinicians. 

PMID- 25849873
TI  - The relationship between regular sports participation and vigilance in male and
      female adolescents.
AB  - The present study investigated the relationship between regular sport
      participation (soccer) and vigilance performance. Two groups of male and female
      adolescents differentiated in terms of their sport participation (athletes, n =
      39, and non-athletes, n = 36) took part in the study. In one session,
      participants performed the Leger Multi-stage fitness test to estimate their
      aerobic fitness level. In the other session, participants completed the
      Psychomotor Vigilance Task (PVT) to evaluate their vigilance performance.
      Perceived arousal prior to the task and motivation toward the task were also
      measured in the PVT session. The results revealed that athletes had better
      cardiovascular fitness and showed better performance in the PVT. However,
      correlation analyses did not show any significant relationship between
      cardiovascular fitness and performance in the PVT. Athletes showed larger scores
      in motivation and perceived arousal measures with respect to non-athletes,
      although, once again, these variables were not correlated with PVT performance.
      Gender differences were observed only in the Leger test, with males showing
      greater fitness level than females. The major outcome of this research points to
      a positive relationship between regular sport participation and vigilance during
      adolescence. This relationship did not seem to be influenced by gender, perceived
      arousal, motivation toward the task or cardiovascular fitness. We discuss our
      results in terms of the different hypotheses put forward in the literature to
      explain the relationship between physical activity and cognitive functioning. 

PMID- 25849875
TI  - Investigating follow-up outcome change using hierarchical linear modeling.
AB  - Individual change in outcome during a one-year follow-up period for 98 patients
      who received either interpretive or supportive psychotherapy was examined using
      hierarchical linear modeling (HLM). This followed a previous study that had
      investigated average (treatment condition) change during follow-up using
      traditional methods of data analysis (repeated measures ANOVA, chi-square tests).
      We also investigated whether two patient personality characteristics-quality of
      object relations (QOR) and psychological mindedness (PM)-predicted individual
      change. HLM procedures yielded findings that were not detected using traditional
      methods of data analysis. New findings indicated that the rate of individual
      change in outcome during follow-up varied significantly among the patients. QOR
      was directly related to favorable individual change for supportive therapy
      patients, but not for patients who received interpretive therapy. The findings
      have implications for determining which patients will show long-term benefit
      following short-term supportive therapy and how to enhance it. The study also
      found significant associations between QOR and final outcome level. 

PMID- 25849876
TI  - Evaluating the phase model of change during short-term psychodynamic
      psychotherapy.
AB  - This study examined the phase model of psychotherapy change (Howard, Lueger,
      Maling, & Martinovich, 1993; Howard, Moras, Brill, Martinovich, & Lutz, 1996) and
      assessed the domains of subjective well-being, symptomatic distress, and
      social/interpersonal functioning during short-term psychodynamic psychotherapy.
      Specifically, we assessed evaluation/third-session to ninth-session changes in a
      group of 20 treated patients. These three domains were examined for both
      statistical and clinically significant change (Jacobson & Truax, 1991). Treatment
      fidelity and credibility were also evaluated. Statistical and clinically
      significant improvement in the domains of subjective well-being and symptom
      distress were evident by the ninth session of short-term dynamic psychotherapy.
      Statistical and reliable improvement were observed in relational functioning
      during the same time period. In addition, changes in both subjective well-being
      and symptomatic distress contributed unique and separate variance to predicting
      changes in social/interpersonal functioning. The results with respect to the
      differential effects predicted by the phase model of change during the early
      course of treatment are discussed. 

PMID- 25849877
TI  - The effects of providing therapists with feedback on patient progress during
      psychotherapy: are outcomes enhanced?
AB  - Patient-focused research attempts to provide information that answers the
      question: Is this treatment benefiting this patient? Although several systems
      have been developed to monitor and provide feedback about a patient's response to
      psychotherapy, few if any have been tested empirically. The current study divided
      609 patients into four groups (two experimental and two control) to determine if
      feedback regarding patient progress, when provided to a therapist, affected
      patient outcome and number of sessions attended. Results showed that feedback
      increased the duration of treatment and improved outcome relative to patients in
      the control condition who were predicted to be treatment failures. Twice as many
      patients in the feedback group achieved clinically significant or reliable change
      and one-third as many were classified as deteriorated by the time treatment
      ended. For those patients who were predicted to have a positive response to
      treatment, feedback to therapists resulted in a reduction in the number of
      treatment sessions without reducing positive outcomes. 

PMID- 25849878
TI  - Psychometric Properties of the Psychotherapy Expectancy Inventory-Revised (PEI
      R).
AB  - The Psychotherapy Expectancy Inventory-Revised (PEI-R) was developed to measure
      clients' expectations of behavior in counseling. An exploratory factor analysis
      of the original PEI-R (Rickers-Ovsiankina, Berzins, Geller, & Rogers, 1971) on a
      sample of clients yielded four factors: approval, advice, audience and
      relationship (Berzins, 1971). The aim of the study presented in this paper is to
      examine the internal construct validity of the PEI-R by means of a confirmatory
      factor analysis on data gathered in a sample of 159 clients. The analysis
      revealed an adequate model fit for the four-dimensional oblique model. However,
      detailed inspection of model fit suggest the possibility of a fifth factor. Data
      concerning the reliability and the relationship with demographics are also
      provided. 

PMID- 25849879
TI  - Schemas, affect consciousness, and cluster C personality pathology: a prospective
      one-year follow-up study of patients in a schema-focused short-term treatment
      program.
AB  - In this prospective study the aim was to investigate the relationship between
      affect consciousness and Cluster C personality pathology (DSM-IV, Axis-II). Forty
      four patients with panic disorder and/or agoraphobia and Cluster C personality
      traits were treated in a schema-focused program comprising a first
      panic/agoraphobia-focused phase and a second personality-focused phase, being
      finally assessed at a one-year follow-up. According to the treatment strategy,
      affect consciousness was expected to change during the second phase, independent
      of change in agoraphobic avoidance being focused in the first phase. Pretreatment
      level of affect consciousness during treatment was related to a reduction in
      avoidant personality pathology (not dependent or obsessive-compulsive) from
      pretreatment to follow-up, while increase in affect consciousness did not
      contribute in the same way. These results indicate that affect consciousness is
      important as a selection criterion, as a parameter in treatment with focus on
      schemas and schema-avoidance, and as a predictor for outcome in agoraphobic
      patients with avoidant personality pathology. 

PMID- 25849880
TI  - Affective indicators of the psychotherapeutic process: an empirical case study.
AB  - By analyzing facial expressions of emotion and the emotional experience of a
      patient and a psychotherapist, we attempted to objectively register unconscious
      interaction processes that could have contributed to the failure of a
      psychotherapy that ended prematurely. In this connection, the affect 'contempt'
      played a particular role. It is made clear how an unconscious enactment results
      in a gap between emotional expression and experience. In addition, the
      countertransference of the psychotherapist is examined and the emotional
      experience is contrasted with her affective behavior. In this study, it is
      demonstrated how this particular psychotherapy failed due to a lack of
      acknowledging the involvement of the interactive dynamics. 

PMID- 25849881
TI  - Helping the Hard-Core Smoker: A Clinician's Guide.

PMID- 25849882
TI  - Socioeconomic position, health behaviors, and racial disparities in cause
      specific infant mortality in Michigan, USA.
AB  - OBJECTIVES: Studies about racial disparities in infant mortality suggest that
      racial differences in socioeconomic position (SEP) and maternal risk behaviors
      explain some, but not all, excess infant mortality among Blacks relative to non
      Hispanic Whites. We examined the contribution of these to disparities in specific
      causes of infant mortality. METHODS: We analyzed data about 2,087,191 mother
      child dyads in Michigan between 1989 and 2005. First, we calculated crude Black
      White infant mortality ratios independently and by specific cause of death.
      Second, we fit multivariable Poisson regression models of infant mortality,
      overall and by cause, adjusting for SEP and maternal risk behaviors. Third, Crude
      Black-White mortality ratios were compared to adjusted predicted probability
      ratios, overall and by specific cause. RESULTS: SEP and maternal risk behaviors
      explained nearly a third of the disparity in infant mortality overall, and over
      25% of disparities in several specific causes including homicide, accident,
      sudden infant death syndrome, and respiratory distress syndrome. However, SEP and
      maternal risk behaviors had little influence on disparities in other specific
      causes, such as septicemia and congenital anomalies. CONCLUSIONS: These findings
      help focus policy attention toward disparities in those specific causes of infant
      mortality most amenable to social and behavioral intervention, as well as
      research attention to disparities in specific causes unexplained by SEP and
      behavioral differences.

PMID- 25849884
TI  - Correction: PDCD10 gene mutations in multiple cerebral cavernous malformations.

PMID- 25849883
TI  - Disparities in long-term cardiovascular disease risk by sexual identity: The
      National Longitudinal Study of Adolescent to Adult Health.
AB  - OBJECTIVE: To examine long-term cardiovascular disease (CVD) risk disparities by
      sexual identity using a nationally representative sample of young adults in the
      United States. METHODS: Data include participants in wave 4 (2008/09; ages 24
      34years) of the National Longitudinal Study of Adolescent to Adult Health (7087
      females; 6340 males). Sexual identity was self-reported (heterosexual, mostly
      heterosexual, bisexual, mostly homosexual, homosexual) and a Framingham-based
      prediction model was used to estimate participants' risk of a CVD event over
      30years. Differences in CVD risk by sexual identity, relative to heterosexuals,
      were calculated with linear regression models adjusted for age, race/ethnicity,
      education, and financial distress. RESULTS: Average 30-year CVD risk was 17.2%
      (95% CI: 16.7, 17.7) in males and 9.0% (95% CI: 8.6, 9.3) in females. Compared to
      heterosexual females, mostly heterosexual (0.8%; 95% CI: 0.2, 1.4) and mostly
      homosexual females (2.8%; 95% CI: 0.8, 4.9) had higher CVD risk. Bisexual and
      homosexual females had higher but not statistically significant CVD risk compared
      to heterosexuals. Among males, differences in CVD risk by sexual identity were
      not statistically significant. CONCLUSION: Sexual identity was associated with
      CVD risk in sexual minority subgroups. Population- and clinic-based prevention
      strategies are needed to minimize disparities in subsequent disease.

PMID- 25849885
TI  - Low pH increases the yield of exosome isolation.
AB  - Exosomes are the extracellular vesicles secreted by various cells. Exosomes
      mediate intercellular communication by delivering a variety of molecules between
      cells. Cancer cell derived exosomes seem to be related with tumor progression and
      metastasis. Tumor microenvironment is thought to be acidic and this low pH
      controls exosome physiology, leading to tumor progression. Despite the importance
      of microenvironmental pH on exosome, most of exosome studies have been performed
      without regard to pH. Therefore, the difference of exosome stability and yield of
      isolation by different pH need to be studied. In this research, we investigated
      the yield of total exosomal protein and RNA after incubation in acidic, neutral
      and alkaline conditioned medium. Representative exosome markers were investigated
      by western blot after incubation of exosomes in different pH. As a result, the
      concentrations of exosomal protein and nucleic acid were significantly increased
      after incubation in the acidic medium compared with neutral medium. The higher
      levels of exosome markers including CD9, CD63 and HSP70 were observed after
      incubation in an acidic environment. On the other hand, no exosomal protein,
      exosomal RNA and exosome markers have been detected after incubation in an
      alkaline condition. In summary, our results indicate that the acidic condition is
      the favorable environment for existence and isolation of exosomes. 

PMID- 25849886
TI  - Effect of TGFbeta on calcium signaling in megakaryocytes.
AB  - TGFbeta is a powerful regulator of megakaryocyte maturation and platelet
      formation. As previously shown for other cell types, TGFbeta may up-regulate the
      expression of the serum & glucocorticoid inducible kinase SGK1, an effect
      requiring p38 kinase. SGK1 has in turn recently been shown to participate in the
      regulation of cytosolic Ca(2+) activity ([Ca(2+)]i) in megakaryocytes and
      platelets. SGK1 phosphorylates the IkappaB kinase (IKKalpha/beta), which in turn
      phosphorylates the inhibitor protein IkappaBalpha resulting in nuclear
      translocation of nuclear factor NFkappaB. Genes up-regulated by NFkappaB include
      Orai1, the pore forming ion channel subunit accomplishing store operated Ca(2+)
      entry (SOCE). The present study explored whether TGFbeta influences Ca(2+)
      signaling in megakaryocytes. [Ca(2+)]i was determined by Fura-2 fluorescence and
      SOCE from the increase of [Ca(2+)]i following re-addition of extracellular Ca(2+)
      after store depletion by removal of extracellular Ca(2+) and inhibition of the
      sarcoendoplasmatic Ca(2+) ATPase (SERCA) with thapsigargin (1 MUM). As a result,
      TGFbeta (60 ng, 24 h) increased SOCE, an effect significantly blunted by p38
      kinase inhibitor Skepinone-L (1 MUM), SGK1 inhibitor EMD638683 (50 MUM) and
      NFkappaB inhibitor wogonin (100 MUM). In conclusion, TGFbeta is a powerful
      regulator of store operated Ca(2+) entry into megakaryocytes, an effect mediated
      by a signaling cascade involving p38 kinase, SGK1 and NFkappaB. 

PMID- 25849887
TI  - Crystal structures of YfiR from Pseudomonas aeruginosa in two redox states.
AB  - YfiBNR is a recently identified c-di-GMP regulatory system involved in bacterial
      biofilm formation. The periplasmic protein YfiR inhibits the diguanylate cyclase
      activity of the inner membrane protein YfiN, whereas YfiB in the outer membrane
      can release this inhibition by sequestration of YfiR. In addition, this system
      may respond to anoxic conditions via YfiR, although the detailed mechanism is
      still unknown. Here we report crystal structures of Pseudomonas aeruginosa YfiR
      in the absence and presence of oxidative glutathione. Our structures reveal the
      overall folding of YfiR for the first time and demonstrate that YfiR exist as a
      dimer. Comparison of the two structures in different redox states revealed a
      broken/formation of one disulfide bond (Cys71-Cys110) and local conformational
      change around the other one (Cys145-Cys152). Mutagenesis studies indicated that
      Cys145-Cys152 plays an important role in maintaining the correct folding of YfiR.

PMID- 25849888
TI  - beta-Catenin expression is regulated by an IRES-dependent mechanism and
      stimulated by paclitaxel in human ovarian cancer cells.
AB  - Paclitaxel (PTX) is commonly used in the chemotherapy of ovarian cancer, but
      resistance occurs in most cases, allowing cancer progression. The Wnt/beta
      catenin pathway has been associated with this resistance, but there are no
      reports on the regulation of beta-catenin expression at the translational level.
      In the present study, we found that PTX induced different transcription and
      translation levels of beta-catenin in the human ovarian cancer cell lines A2780
      and SKOV3. We also demonstrated that beta-catenin mRNA contained an internal
      ribosome entry segment (IRES) that regulated its translation. Using gene
      transfection and reporter assays, we revealed that the entire CTNNB1 5'
      untranslated region (UTR) contributed to IRES activity. Interestingly, we found
      that c-myc and cyclin D1 increased significantly in transfected cells with
      increasing PTX concentration, and cell-survival rates remained at 60% while the
      PTX concentration increased. Suppressing beta-catenin resulted in decreased
      expression of c-myc and cyclin D1 and made these cells less resistant. These
      results indicate that beta-catenin translation is initiated via the IRES and this
      is regulated by PTX, suggesting that regulation of the IRES-dependent translation
      of beta-catenin may be involved in the cancer cell response to PTX treatment. 

PMID- 25849890
TI  - Green tea catechins enhance norepinephrine-induced lipolysis via a protein kinase
      A-dependent pathway in adipocytes.
AB  - Green tea catechins have been shown to attenuate obesity in animals and humans.
      The catechins activate adenosine monophosphate-activated protein kinase (AMPK),
      and thereby increase fatty acid oxidation in liver and skeletal muscles. Green
      tea catechins have also been shown to reduce body fat in humans. However, the
      effect of the catechins on lipolysis in adipose tissue has not been fully
      understood. The aim of this study was to clarify the effect of green tea
      catechins on lipolysis in adipocytes and to elucidate the underlying mechanism.
      Differentiated mouse adipocyte cell line (3T3-L1) was stimulated with green tea
      catechins in the presence or absence of norepinephrine. Glycerol and free fatty
      acids in the media were measured. Phosphorylation of hormone-sensitive lipase
      (HSL) was determined by Western blotting, and the mRNA expression levels of HSL,
      adipose triglyceride lipase (ATGL), and perilipin were determined by quantitative
      RT-PCR. The cells were treated with inhibitors of protein kinase A (PKA), protein
      kinase C (PKC), protein kinase G (PKG), or mitogen-activated protein kinase
      (MAPK) to determine the responsible pathway. Treatment of 3T3-L1 adipocytes with
      green tea catechins increased the level of glycerol and free fatty acids released
      into the media in the presence, but not absence, of norepinephrine, and increased
      the level of phosphorylated HSL in the cells. The catechins also increased mRNA
      and protein levels of HSL and ATGL. PKA inhibitor (H89) attenuated the catechin
      induced increase in glycerol release and HSL phosphorylation. The results
      demonstrate that green tea catechins enhance lipolysis in the presence of
      norepinephrine via a PKA-dependent pathway in 3T3-L1 adipocytes, providing a
      potential mechanism by which green tea catechins could reduce body fat. 

PMID- 25849889
TI  - Role of methylthioadenosine/S-adenosylhomocysteine nucleosidase in Vibrio
      cholerae cellular communication and biofilm development.
AB  - In Vibrio cholerae, the genes required for biofilm development are repressed by
      quorum sensing at high cell density due to the accumulation in the medium of two
      signaling molecules, cholera autoinducer 1 (CAI-1) and autoinducer 2 (AI-2). A
      significant fraction of toxigenic V. cholerae isolates, however, exhibit
      dysfunctional quorum sensing pathways. It was reported that transition state
      analogs of the enzyme methylthioadenosine/S-adenosylhomocysteine nucleosidase
      (MtnN) required to make AI-2 inhibited biofilm formation in the prototype quorum
      sensing-deficient strain N16961. This finding prompted us to examine the role of
      both autoinducers and MtnN in biofilm development and virulence gene expression
      in a quorum sensing-deficient genetic background. Here we show that deletion of
      mtnN encoding methylthioadenosine/S-adenosylhomocysteine nucleosidase, cqsA (CAI
      1), and/or luxS (AI-2) do not prevent biofilm development. However, two
      independent mtnN mutants exhibited diminished growth rate and motility in swarm
      agar plates suggesting that, under certain conditions, MtnN could influence
      biofilm formation indirectly. Nevertheless, MtnN is not required for the
      development of a mature biofilm. 

PMID- 25849891
TI  - Involvement of the orexin system in sympathetic nerve regulation.
AB  - Orexin, also known as hypocretin, is a secreted neuropeptide implicated in the
      regulation of sleep and food intake. In the present study, we examined the
      importance of orexin in regulation of the sympathetic nervous system using an
      orexin/ataxin-3 transgenic (OXTg) rat, which has a minimal number of orexin
      neurons. RT-PCR analysis identified expression of prepro-orexin and orexin
      receptor-1 (OX1R) in the superior cervical ganglion (SCG), and expression of
      another receptor (OX2R) was marginal in the wild-type rat. The orexin/ataxin-3
      transgenic rat showed increased expression of OX1R and OX2R, whereas expression
      of prepro-orexin was undetectable, suggesting a compensatory increase in both
      receptors. In the ECG recording (R-R interval), orexin/ataxin-3 transgenic rats
      showed decreased responsiveness to the beta-adrenergic blocker propranolol.
      Furthermore, OXTg rats had deteriorated R-R interval regulation, indicating
      involvement of the orexin system in sympathetic nerve regulation. This was
      accompanied by decreased baroreflex and responsiveness to beta-adrenergic blocker
      in blood pressure recording, also suggesting involvement of the orexin system in
      sympathetic nerve regulation. Histological examination revealed hypotrophic
      changes in the transgenic heart, suggesting involvement of the orexin system in
      cardiac development. Taken together, our present results indicate involvement of
      the orexin system in sympathetic nerve control. 

PMID- 25849892
TI  - Diverse effects of LPA4, LPA5 and LPA6 on the activation of tumor progression in
      pancreatic cancer cells.
AB  - Lysophosphatidic acid (LPA) is an extracellular biological lipid which interacts
      with G protein-coupled LPA receptors (LPA1 to LPA6). LPA signaling via LPA
      receptors mediates several cellular responses. In the present study, to assess
      the roles of LPA4, LPA5 and LPA6 in cellular functions of pancreatic cancer
      cells, we generated LPA receptor knockdown cells from PANC-1 cells (PANC-sh4,
      PANC-sh5 and PANC-sh6 cells, respectively). In cell motility assay, PANC-sh4 and
      PANC-sh5 cells enhanced the cell motile activities, compared with control cells.
      In contrast, the cell motile activity of PANC-sh6 cells was suppressed. The
      invasive activities of PANC-sh4 and PANC-sh5 cells were markedly stimulated,
      while PANC-sh6 cells showed the low invasive activity. In colony assay, PANC-sh4
      and PANC-sh5 cells formed the large sized colonies, but not PANC-sh6 cells. When
      endothelial cells were incubated with supernatants from PANC-sh4 and PANC-sh5
      cells, the cell motility and tube formation of endothelial cells were
      significantly induced, but not PANC-sh6 cells. These results suggest that the
      diverse roles of LPA4, LPA5 and LPA6 are involved in the activation of tumor
      progression in pancreatic cancer cells. 

PMID- 25849893
TI  - TYK2 protein-coding variants protect against rheumatoid arthritis and
      autoimmunity, with no evidence of major pleiotropic effects on non-autoimmune
      complex traits.
AB  - Despite the success of genome-wide association studies (GWAS) in detecting a
      large number of loci for complex phenotypes such as rheumatoid arthritis (RA)
      susceptibility, the lack of information on the causal genes leaves important
      challenges to interpret GWAS results in the context of the disease biology. Here,
      we genetically fine-map the RA risk locus at 19p13 to define causal variants, and
      explore the pleiotropic effects of these same variants in other complex traits.
      First, we combined Immunochip dense genotyping (n = 23,092 case/control samples),
      Exomechip genotyping (n = 18,409 case/control samples) and targeted exon
      sequencing (n = 2,236 case/controls samples) to demonstrate that three protein
      coding variants in TYK2 (tyrosine kinase 2) independently protect against RA:
      P1104A (rs34536443, OR = 0.66, P = 2.3 x 10(-21)), A928V (rs35018800, OR = 0.53,
      P = 1.2 x 10(-9)), and I684S (rs12720356, OR = 0.86, P = 4.6 x 10(-7)). Second,
      we show that the same three TYK2 variants protect against systemic lupus
      erythematosus (SLE, Pomnibus = 6 x 10(-18)), and provide suggestive evidence that
      two of the TYK2 variants (P1104A and A928V) may also protect against inflammatory
      bowel disease (IBD; P(omnibus) = 0.005). Finally, in a phenome-wide association
      study (PheWAS) assessing >500 phenotypes using electronic medical records (EMR)
      in >29,000 subjects, we found no convincing evidence for association of P1104A
      and A928V with complex phenotypes other than autoimmune diseases such as RA, SLE
      and IBD. Together, our results demonstrate the role of TYK2 in the pathogenesis
      of RA, SLE and IBD, and provide supporting evidence for TYK2 as a promising drug
      target for the treatment of autoimmune diseases.

PMID- 25849894
TI  - Human Parvovirus B19 and blood product safety: a tale of twenty years of
      improvements.

PMID- 25849895
TI  - Spectroscopic studies reveal that the heme regulatory motifs of heme oxygenase-2
      are dynamically disordered and exhibit redox-dependent interaction with heme.
AB  - Heme oxygenase (HO) catalyzes a key step in heme homeostasis: the O2- and NADPH
      cytochrome P450 reductase-dependent conversion of heme to biliverdin, Fe, and CO
      through a process in which the heme participates both as a prosthetic group and
      as a substrate. Mammals contain two isoforms of this enzyme, HO2 and HO1, which
      share the same alpha-helical fold forming the catalytic core and heme binding
      site, as well as a membrane spanning helix at their C-termini. However, unlike
      HO1, HO2 has an additional 30-residue N-terminus as well as two cysteine-proline
      sequences near the C-terminus that reside in heme regulatory motifs (HRMs). While
      the role of the additional N-terminal residues of HO2 is not yet understood, the
      HRMs have been proposed to reversibly form a thiol/disulfide redox switch that
      modulates the affinity of HO2 for ferric heme as a function of cellular redox
      poise. To further define the roles of the N- and C-terminal regions unique to
      HO2, we used multiple spectroscopic techniques to characterize these regions of
      the human HO2. Nuclear magnetic resonance spectroscopic experiments with HO2
      demonstrate that, when the HRMs are in the oxidized state (HO2(O)), both the
      extra N-terminal and the C-terminal HRM-containing regions are disordered.
      However, protein NMR experiments illustrate that, under reducing conditions, the
      C-terminal region gains some structure as the Cys residues in the HRMs undergo
      reduction (HO2(R)) and, in experiments employing a diamagnetic protoporphyrin,
      suggest a redox-dependent interaction between the core and the HRM domains.
      Further, electron nuclear double resonance and X-ray absorption spectroscopic
      studies demonstrate that, upon reduction of the HRMs to the sulfhydryl form, a
      cysteine residue from the HRM region ligates to a ferric heme. Taken together
      with EPR measurements, which show the appearance of a new low-spin heme signal in
      reduced HO2, it appears that a cysteine residue(s) in the HRMs directly interacts
      with a second bound heme. 

PMID- 25849897
TI  - Monaural Auditory Cue Affects the Process of Choosing the Initial Swing Leg in
      Gait Initiation.
AB  - The authors investigated the effect of an auditory cue on the choice of the
      initial swing leg in gait initiation. Healthy humans initiated a gait in response
      to a monaural or binaural auditory cue. When the auditory cue was given in the
      ear ipsilateral to the preferred leg side, the participants consistently
      initiated their gait with the preferred leg. In the session in which the side of
      the monaural auditory cue was altered trial by trial randomly, the probability of
      initiating the gait with the nonpreferred leg increased when the auditory cue was
      given in the ear contralateral to the preferred leg side. The probability of
      choosing the nonpreferred leg did not increase significantly when the auditory
      cue was given in the ear contralateral to the preferred leg side in the session
      in which the auditory cue was constantly given in the ear contralateral to the
      preferred leg side. The reaction time of anticipatory postural adjustment was
      shortened, but the probability of choosing the nonpreferred leg was not
      significantly increased when the gait was initiated in response to a binaural
      auditory cue. An auditory cue in the ear contralateral to the preferred leg side
      weakens the preference for choosing the preferred leg as the initial swing leg in
      gait initiation when the side of the auditory cue is unpredictable. 

PMID- 25849896
TI  - Impacts of nucleotide fixation during soybean domestication and improvement.
AB  - BACKGROUND: Plant domestication involves complex morphological and physiological
      modification of wild species to meet human needs. Artificial selection during
      soybean domestication and improvement results in substantial phenotypic
      divergence between wild and cultivated soybeans. Strong selective pressure on
      beneficial phenotypes could cause nucleotide fixations in the founder population
      of soybean cultivars in quite a short time. RESULTS: Analysis of available
      sequencing accessions estimates that ~5.3 million single nucleotide variations
      reach saturation in cultivars, and then ~9.8 million in soybean germplasm.
      Selective sweeps defined by loss of genetic diversity reveal 2,255 and 1,051
      genes were involved in domestication and subsequent improvement, respectively.
      Both processes introduced ~0.1 million nucleotide fixations, which contributed to
      the divergence of wild and cultivated soybeans. Meta-analysis of reported
      quantitative trait loci (QTL) and selective signals with nucleotide fixation
      identifies a series of putative candidate genes responsible for 13 agronomically
      important traits. Nucleotide fixation mediated by artificial selection affected
      diverse molecular functions and biological reactions that associated with soybean
      morphological and physiological changes. Of them, plant-pathogen interactions are
      of particular relevance as selective nucleotide fixations happened in disease
      resistance genes, cyclic nucleotide-gated ion channels and terpene synthases.
      CONCLUSIONS: Our analysis provides insights into the impacts of nucleotide
      fixation during soybean domestication and improvement, which would facilitate
      future QTL mapping and molecular breeding practice.

PMID- 25849898
TI  - Human factors/ergonomics implications of big data analytics: Chartered Institute
      of Ergonomics and Human Factors annual lecture.
AB  - In recent years, advances in sensor technology, connectedness and computational
      power have come together to produce huge data-sets. The treatment and analysis of
      these data-sets is known as big data analytics (BDA), and the somewhat related
      term data mining. Fields allied to human factors/ergonomics (HFE), e.g.
      statistics, have developed computational methods to derive meaningful, actionable
      conclusions from these data bases. This paper examines BDA, often characterised
      by volume, velocity and variety, giving examples of successful BDA use. This
      examination provides context by considering examples of using BDA on human data,
      using BDA in HFE studies, and studies of how people perform BDA. Significant
      issues for HFE are the reliance of BDA on correlation rather than hypotheses and
      theory, the ethics of BDA and the use of HFE in data visualisation. 

PMID- 25849899
TI  - Cell type-specific responses to wingless, hedgehog and decapentaplegic are
      essential for patterning early eye-antenna disc in Drosophila.
AB  - The Drosophila eye-antenna imaginal disc (ead) is a flattened sac of two-layered
      epithelia, from which most head structures are derived. Secreted morphogens like
      Wingless (Wg), Hedgehog (Hh), and Decapentaplegic (Dpp) are important for early
      patterning of ead, but the underlying mechanisms are still largely unknown. To
      understand how these morphogens function in the ead of early larval stages, we
      used wg-LacZ and dpp-Gal4 markers for the examination of wild-type and mutant
      eads. We found that the ead immediately after hatching was crescent-shaped with
      the Bolwig's nerve at the ventral edge, suggesting that it consists of dorsal
      domain. In a subsequent step, transcriptional induction of dpp in the cells along
      the Bolwig's nerve was followed by rapid growth of the ventral domain. Both Wg
      and Hh were required for the formation of the ventral domain. Wg was crucial for
      the growth of the entire ead, but Hh was essential for cell division only in the
      dorsal domain. In the ventral domain, Hh regulated dpp transcription. Based on
      these data, we propose that signaling among distinct groups of cells expressing
      Wg, Dpp, or Hh in the ead of the first-instar larvae are critical for coordinated
      growth and patterning of ead. 

PMID- 25849901
TI  - Interferometric nanoporous anodic alumina photonic coatings for optical sensing.
AB  - Herein, we present a systematic study on the development, optical optimization
      and sensing applicability of colored photonic coatings based on nanoporous anodic
      alumina films grown on aluminum substrates. These optical nanostructures, so
      called distributed Bragg reflectors (NAA-DBRs), are fabricated by galvanostatic
      pulse anodization process, in which the current density is altered in a periodic
      manner in order to engineer the effective medium of the resulting photonic
      coatings. As-prepared NAA-DBR photonic coatings present brilliant interference
      colors on the surface of aluminum, which can be tuned at will within the UV
      visible spectrum by means of the anodization profile. A broad library of NAA-DBR
      colors is produced by means of different anodization profiles. Then, the
      effective medium of these NAA-DBR photonic coatings is systematically assessed in
      terms of optical sensitivity, low limit of detection and linearity by
      reflectometric interference spectroscopy (RIfS) in order to optimize their
      nanoporous structure toward optical sensors with enhanced sensing performance.
      Finally, we demonstrate the applicability of these photonic nanostructures as
      optical platforms by selectively detecting gold(iii) ions in aqueous solutions.
      The obtained results reveal that optimized NAA-DBR photonic coatings can achieve
      an outstanding sensing performance for gold(iii) ions, with a sensitivity of
      22.16 nm MUM(-1), a low limit of detection of 0.156 MUM (i.e. 30.7 ppb) and
      excellent linearity within the working range (0.9983). 

PMID- 25849900
TI  - Epigenome editing by a CRISPR-Cas9-based acetyltransferase activates genes from
      promoters and enhancers.
AB  - Technologies that enable targeted manipulation of epigenetic marks could be used
      to precisely control cell phenotype or interrogate the relationship between the
      epigenome and transcriptional control. Here we describe a programmable, CRISPR
      Cas9-based acetyltransferase consisting of the nuclease-null dCas9 protein fused
      to the catalytic core of the human acetyltransferase p300. The fusion protein
      catalyzes acetylation of histone H3 lysine 27 at its target sites, leading to
      robust transcriptional activation of target genes from promoters and both
      proximal and distal enhancers. Gene activation by the targeted acetyltransferase
      was highly specific across the genome. In contrast to previous dCas9-based
      activators, the acetyltransferase activates genes from enhancer regions and with
      an individual guide RNA. We also show that the core p300 domain can be fused to
      other programmable DNA-binding proteins. These results support targeted
      acetylation as a causal mechanism of transactivation and provide a robust tool
      for manipulating gene regulation. 

PMID- 25849902
TI  - Adult active transport in the Netherlands: an analysis of its contribution to
      physical activity requirements.
AB  - INTRODUCTION: Modern, urban lifestyles have engineered physical activity out of
      everyday life and this presents a major threat to human health. The Netherlands
      is a world leader in active travel, particularly cycling, but little research has
      sought to quantify the cumulative amount of physical activity through everyday
      walking and cycling. METHODS: Using data collected as part of the Dutch National
      Travel Survey (2010 - 2012), this paper determines the degree to which Dutch
      walking and cycling contributes to meeting minimum level of physical activity of
      150 minutes of moderate intensity aerobic activity throughout the week. The
      sample includes 74,465 individuals who recorded at least some travel on the day
      surveyed. As physical activity benefits are cumulative, all walking and cycling
      trips are analysed, including those to and from public transport. These trips are
      then converted into an established measure of physical activity intensity, known
      as metabolic equivalents of tasks. Multivariate Tobit regression models were
      performed on a range of socio-demographic, transport resources, urban form and
      meteorological characteristics. RESULTS: The results reveal that Dutch men and
      women participate in 24 and 28 minutes of daily physical activity through walking
      and cycling, which is 41% and 55% more than the minimum recommended level. It
      should be noted however that some 57% of the entire sample failed to record any
      walking or cycling, and an investigation of this particular group serves as an
      important topic of future research. Active transport was positively related with
      age, income, bicycle ownership, urban density and air temperature. Car ownership
      had a strong negative relationship with physically active travel. CONCLUSION: The
      results of this analysis demonstrate the significance of active transport to
      counter the emerging issue of sedentary lifestyle disease. The Dutch experience
      provides other countries with a highly relevant case study in the creation of
      environments and cultures that support healthy, active living.

PMID- 25849903
TI  - Effects of exenatide on postprandial vascular endothelial dysfunction in type 2
      diabetes mellitus.
AB  - BACKGROUND: Basic studies have shown that glucagon-like peptide-1 (GLP-1) analogs
      exert a direct protective effect on the vascular endothelium in addition to their
      indirect effects on postprandial glucose and lipid metabolism. GLP-1 analogs are
      also reported to inhibit postprandial vascular endothelial dysfunction. This
      study examined whether the GLP-1 analog exenatide inhibits postprandial vascular
      endothelial dysfunction in patients with type 2 diabetes mellitus (T2DM).
      METHODS: Seventeen patients with T2DM underwent a meal tolerance test to examine
      changes in postprandial vascular endothelial function and in glucose and lipid
      metabolism, both without exenatide (baseline) and after a single subcutaneous
      injection of 10 MUg exenatide. Vascular endothelial function was determined using
      reactive hyperemia index (RHI) measured by peripheral arterial tonometry before
      and 120 min after the meal loading test. The primary endpoint was the difference
      in changes in postprandial vascular endothelial function between the baseline and
      exenatide tests. RESULTS: The natural logarithmically-scaled RHI (L_RHI) was
      significantly lower after the baseline meal test but not in the exenatide test.
      The use of exenatide resulted in a significant decrease in triglycerides (TG)
      area under the curve and coefficient of variation (CV). The change in L_RHI
      correlated with changes in CV of triglycerides and HDL-cholesterol. Multivariate
      analysis identified changes in triglyceride CV as the only determinant of changes
      in L_RHI, contributing to 41% of the observed change. CONCLUSIONS: Exenatide
      inhibited postprandial vascular endothelial dysfunction after the meal loading
      test, suggesting that exenatide has a multiphasic anti-atherogenic action
      involving not only glucose but also lipid metabolism. TRIAL REGISTRATION:
      ClinicalTrials.gov: UMIN000015699.

PMID- 25849906
TI  - Correction: stereoscopic analysis of optic nerve head parameters in primary open
      angle glaucoma: the glaucoma stereo analysis study.

PMID- 25849905
TI  - Brain-derived neurotrophic factor ameliorates learning deficits in a rat model of
      Alzheimer's disease induced by abeta1-42.
AB  - An emerging body of data suggests that the early onset of Alzheimer's disease
      (AD) is associated with decreased brain-derived neurotrophic factor (BDNF).
      Because BDNF plays a critical role in the regulation of high-frequency synaptic
      transmission and long-term potentiation in the hippocampus, the up-regulation of
      BDNF may rescue cognitive impairments and learning deficits in AD. In the present
      study, we investigated the effects of hippocampal BDNF in a rat model of AD
      produced by a ventricle injection of amyloid-beta1-42 (Abeta1-42). We found that
      a ventricle injection of Abeta1-42 caused learning deficits in rats subjected to
      the Morris water maze and decreased BDNF expression in the hippocampus. Chronic
      intra-hippocampal BDNF administration rescued learning deficits in the water
      maze, whereas infusions of NGF and NT-3 did not influence the behavioral
      performance of rats injected with Abeta1-42. Furthermore, the BDNF-related
      improvement in learning was ERK-dependent because the inhibition of ERK, but not
      JNK or p38, blocked the effects of BDNF on cognitive improvement in rats injected
      with Abeta1-42. Together, our data suggest that the up-regulation of BDNF in the
      hippocampus via activation of the ERK signaling pathway can ameliorate Abeta1-42
      induced learning deficits, thus identifying a novel pathway through which BDNF
      protects against AD-related cognitive impairments. The results of this research
      may shed light on a feasible therapeutic approach to control the progression of
      AD. 

PMID- 25849907
TI  - Periplasmic quality control in biogenesis of outer membrane proteins.
AB  - The beta-barrel outer membrane proteins (OMPs) are integral membrane proteins
      that reside in the outer membrane of Gram-negative bacteria and perform a diverse
      range of biological functions. Synthesized in the cytoplasm, OMPs must be
      transported across the inner membrane and through the periplasmic space before
      they are assembled in the outer membrane. In Escherichia coli, Skp, SurA and DegP
      are the most prominent factors identified to guide OMPs across the periplasm and
      to play the role of quality control. Although extensive genetic and biochemical
      analyses have revealed many basic functions of these periplasmic proteins, the
      mechanism of their collaboration in assisting the folding and insertion of OMPs
      is much less understood. Recently, biophysical approaches have shed light on the
      identification of the intricate network. In the present review, we summarize
      recent advances in the characterization of these key factors, with a special
      emphasis on the multifunctional protein DegP. In addition, we present our
      proposed model on the periplasmic quality control in biogenesis of OMPs. 

PMID- 25849904
TI  - Hydrogen sulfide-based therapeutics: exploiting a unique but ubiquitous
      gasotransmitter.
AB  - Hydrogen sulfide (H2S) has become recognized as an important signalling molecule
      throughout the body, contributing to many physiological and pathological
      processes. In recent years, improved methods for measuring H2S levels and the
      availability of a wider range of H2S donors and more selective inhibitors of H2S
      synthesis have helped to more accurately identify the many biological effects of
      this highly reactive gaseous mediator. Animal studies of several H2S-releasing
      drugs have demonstrated considerable promise for the safe treatment of a wide
      range of disorders. Several such drugs are now in clinical trials. 

PMID- 25849908
TI  - Molecular simulation studies of hydrophobic gating in nanopores and ion channels.
AB  - Gating in channels and nanopores plays a key role in regulating flow of ions
      across membranes. Molecular simulations provide a 'computational microscope'
      which enables us to examine the physical nature of gating mechanisms at the level
      of the single channel molecule. Water enclosed within the confines of a nanoscale
      pore may exhibit unexpected behaviour. In particular, if the molecular surfaces
      lining the pore are hydrophobic this promotes de-wetting of the pore. De-wetting
      is observed as stochastic liquid-vapour transitions within a pore, and may lead
      to functional closure of a pore to the flow of ions and/or water. Such behaviour
      was first observed in simulations of simple model nanopores and referred to as
      'hydrophobic gating'. Simulations of both the nicotinic acetylcholine receptor
      and of TWIK-1 potassium channels (the latter alongside experimental studies)
      suggest hydrophobic gating may occur in some biological ion channels. Current
      studies are focused on designing hydrophobic gates into biomimetic nanopores. 

PMID- 25849909
TI  - Elucidating ligand binding and channel gating mechanisms in pentameric ligand
      gated ion channels by atomistic simulations.
AB  - Pentameric ligand-gated ion channels (pLGICs) are important biomolecules that
      mediate fast synaptic transmission. Their malfunctions are linked to serious
      neuronal disorders and they are major pharmaceutical targets; in invertebrates,
      they are involved in insecticide resistance. The complexity of pLGICs and the
      limited crystallographic information available prevent a detailed understanding
      of how they function. State-of-the-art computational techniques are therefore
      crucial to build an accurate picture at the atomic level of the mechanisms which
      drive the activation of pLGICs, complementing the available experimental data. We
      have used a series of simulation methods, including homology modelling, ligand
      protein docking, density functional theory, molecular dynamics and metadynamics,
      a powerful scheme for accelerating rare events, with the guidance of mutagenesis
      electrophysiology experiments, to explore ligand-binding mechanisms, the effects
      of mutations and the potential role of a proline molecular switch for the gating
      of the ion channels. Results for the insect RDL receptor, the GABAC receptor, the
      5-HT3 receptor and the nicotinic acetylcholine receptor will be reviewed. 

PMID- 25849910
TI  - High-resolution free energy landscape analysis of protein folding.
AB  - The free energy landscape can provide a quantitative description of folding
      dynamics, if determined as a function of an optimally chosen reaction coordinate.
      The profile together with the optimal coordinate allows one to directly determine
      such basic properties of folding dynamics as the configurations of the minima and
      transition states, the heights of the barriers, the value of the pre-exponential
      factor and its relation to the transition path times. In the present study, we
      review the framework, in particular, the approach to determine such an optimal
      coordinate, and its application to the analysis of simulated protein folding
      dynamics. 

PMID- 25849911
TI  - The membranes of Gram-negative bacteria: progress in molecular modelling and
      simulation.
AB  - Molecular modelling and simulations have been employed to study the membranes of
      Gram-negative bacteria for over 20 years. Proteins native to these membranes, as
      well as antimicrobial peptides and drug molecules have been studied using
      molecular dynamics simulations in simple models of membranes, usually only
      comprising one lipid species. Thus, traditionally, the simulations have reflected
      the majority of in vitro membrane experimental setups, enabling observations from
      the latter to be rationalized at the molecular level. In the last few years, the
      sophistication and complexity of membrane models have improved considerably, such
      that the heterogeneity of the lipid and protein composition of the membranes can
      now be considered both at the atomistic and coarse-grain levels of granularity.
      Importantly this means relevant biology is now being retained in the models,
      thereby linking the in silico and in vivo scenarios. We discuss recent progress
      in simulations of proteins in simple lipid bilayers, more complex membrane models
      and finally describe some efforts to overcome timescale limitations of atomistic
      molecular dynamics simulations of bacterial membranes.

PMID- 25849912
TI  - Is the cellular and molecular machinery docile in the stationary phase of
      Escherichia coli?
AB  - The bacterial cell envelope retains a highly dense cytoplasm. The properties of
      the cytoplasm change with the metabolic state of the cell, the logarithmic phase
      (log) being highly active and the stationary phase metabolically much slower.
      Under the differing growth phases, many different types of stress mechanisms are
      activated in order to maintain cellular integrity. One such response in
      enterobacteria is the phage shock protein (Psp) response that enables adaptation
      to the inner membrane (IM) stress. The Psp system consists of a transcriptional
      activator PspF, negative regulator PspA, signal sensors PspBC, with PspA and PspG
      acting as effectors. The single molecule imaging of the PspF showed the existence
      of dynamic communication between the nucleoid-bound states of PspF and membrane
      via negative regulator PspA and PspBC sensors. The movement of proteins in the
      cytoplasm of bacterial cells is often by passive diffusion. It is plausible that
      the dynamics of the biomolecules differs with the state of the cytoplasm
      depending on the growth phase. Therefore, the Psp response proteins might
      encounter the densely packed glass-like properties of the cytoplasm in the
      stationary phase, which can influence their cellular dynamics and function. By
      comparing the properties of the log and stationary phases, we find that the
      dynamics of PspF are influenced by the growth phase and may be controlled by the
      changes in the cytoplasmic fluidity.

PMID- 25849914
TI  - Life in extreme environments: single molecule force spectroscopy as a tool to
      explore proteins from extremophilic organisms.
AB  - Extremophiles are organisms which survive and thrive in extreme environments. The
      proteins from extremophilic single-celled organisms have received considerable
      attention as they are structurally stable and functionally active under extreme
      physical and chemical conditions. In this short article, we provide an
      introduction to extremophiles, the structural adaptations of proteins from
      extremophilic organisms and the exploitation of these proteins in industrial
      applications. We provide a review of recent developments which have utilized
      single molecule force spectroscopy to mechanically manipulate proteins from
      extremophilic organisms and the information which has been gained about their
      stability, flexibility and underlying energy landscapes. 

PMID- 25849913
TI  - Probing the kinetic and thermodynamic consequences of the tetraloop/tetraloop
      receptor monovalent ion-binding site in P4-P6 RNA by smFRET.
AB  - Structured RNA molecules play roles in central biological processes and
      understanding the basic forces and features that govern RNA folding kinetics and
      thermodynamics can help elucidate principles that underlie biological function.
      Here we investigate one such feature, the specific interaction of monovalent
      cations with a structured RNA, the P4-P6 domain of the Tetrahymena ribozyme. We
      employ single molecule FRET (smFRET) approaches as these allow determination of
      folding equilibrium and rate constants over a wide range of stabilities and thus
      allow direct comparisons without the need for extrapolation. These experiments
      provide additional evidence for specific binding of monovalent cations, Na+ and
      K+, to the RNA tetraloop-tetraloop receptor (TL-TLR) tertiary motif. These ions
      facilitate both folding and unfolding, consistent with an ability to help order
      the TLR for binding and further stabilize the tertiary contact subsequent to
      attainment of the folding transition state. 

PMID- 25849915
TI  - Modelling biomacromolecular assemblies with continuum mechanics.
AB  - We have developed a continuum mechanical description of proteins using a finite
      element algorithm which has been generalized to include thermal fluctuations and
      which is therefore known as fluctuating finite element analysis (FFEA). Whereas
      conventional molecular dynamics (MD) simulations provide a trajectory in which
      each individual atomic position fluctuates, a FFEA trajectory shows how the
      overall shape of the protein changes due to thermal agitation. We describe the
      theoretical background to FFEA, its relationship to more established biomolecular
      modelling methods and provide examples of its application to the mesoscale
      biomolecular dynamics of the molecular motor dynein. 

PMID- 25849916
TI  - Enzymatic protein depalmitoylation by acyl protein thioesterases.
AB  - Protein palmitoylation is a dynamic post-translational modification, where the 16
      carbon fatty acid, palmitate, is added to cysteines of proteins to modulate
      protein sorting, targeting and signalling. Palmitate removal from proteins is
      mediated by acyl protein thioesterases (APTs). Although initially identified as
      lysophospholipases, increasing evidence suggests APT1 and APT2 are the major APTs
      that mediate the depalmitoylation of diverse cellular substrates. Here, we
      describe the conserved functions of APT1 and APT2 across organisms and discuss
      the possibility that these enzymes are members of a larger family of
      depalmitoylation enzymes. 

PMID- 25849917
TI  - Postsynaptic nanodomains generated by local palmitoylation cycles.
AB  - Precise regulation of protein assembly at specialized membrane domains is
      essential for diverse cellular functions including synaptic transmission.
      However, it is incompletely understood how protein clustering at the plasma
      membrane is initiated, maintained and controlled. Protein palmitoylation, a
      common post-translational modification, regulates protein targeting to the plasma
      membrane. Such modified proteins are enriched in these specialized membrane
      domains. In this review, we focus on palmitoylation of PSD-95, which is a major
      postsynaptic scaffolding protein and makes discrete postsynaptic nanodomains in a
      palmitoylation-dependent manner and discuss a determinant role of local
      palmitoylation cycles in creating highly localized hotspots at the membrane where
      specific proteins concentrate to organize functional domains. 

PMID- 25849918
TI  - Aberrant palmitoylation in Huntington disease.
AB  - Huntington disease (HD) is an adult-onset neurodegenerative disease caused by a
      CAG expansion in the HTT gene. HD is characterized by striatal atrophy and is
      associated with motor, cognitive and psychiatric deficits. In the presence of the
      HD mutation, the interactions between huntingtin (HTT) and huntingtin interacting
      protein 14 (HIP14 or DHHC17) and HIP14-like (DHHC13, a HIP14 orthologue),
      palmitoyl acyltransferases for HTT, are disturbed, resulting in reduced
      palmitoylation of HTT. Genetic ablation of either Hip14 or Hip14l recapitulates
      many features of HD, including striatal atrophy and motor deficits. However,
      there are no changes in palmitoylation of HTT in either mouse model and,
      subsequently, the similarities between the phenotypes of these two mouse models
      and the HD mouse model are believed to result from underpalmitoylation of other
      HIP14 and HIP14L substrates. HTT acts as a modulator of HIP14 activity such that
      in the presence of the HD mutation, HIP14 is less active. Consequently, HIP14
      substrates are less palmitoylated, leading to neuronal toxicity. This suggests
      that altered HIP14-HTT and HIP14L-HTT interactions in the presence of the HD
      mutation reduces palmitoylation and promotes mislocalization of HTT and other
      HIP14/HIP14L substrates. Ultimately, HD may be, in part, a disease of altered
      palmitoylation.

PMID- 25849920
TI  - The zDHHC family of S-acyltransferases.
AB  - The discovery of the zDHHC family of S-acyltransferase enzymes has been one of
      the major breakthroughs in the S-acylation field. Now, more than a decade since
      their discovery, major questions centre on profiling the substrates of individual
      zDHHC enzymes (there are 24 ZDHHC genes and several hundred S-acylated proteins),
      defining the mechanisms of enzyme-substrate specificity and unravelling the
      importance of this enzyme family for cellular physiology and pathology. 

PMID- 25849919
TI  - Wnt acylation and its functional implication in Wnt signalling regulation.
AB  - Wnt proteins are conserved signalling molecules that have an essential role in
      regulating diverse processes during embryogenesis and adult tissue homoeostasis.
      Wnts are post-translationally modified by palmitoylation, which is essential for
      Wnt secretion and function. Intriguingly, the crystal structure of XWnt8 in
      complex with the extracellular domain of the Frizzled 8 cysteine-rich domain
      (Fzd8-CRD) revealed that Wnts use the fatty acid as a 'hotspot' residue to engage
      its receptor, which is a unique mode of receptor-ligand recognition. In addition,
      there are several lines of evidence suggesting that Wnts engage several
      signalling modulators and alternative receptors by means of fatty acids as a
      critical contact residue. In the present article, we review our current
      understanding of Wnt acylation and its functional role in Wnt signalling
      regulation. 

PMID- 25849922
TI  - Post-translational myristoylation at the cross roads of cell death, autophagy and
      neurodegeneration.
AB  - In a little more than a decade, post-translational myristoylation (PTMyr) has
      become an established post-translational modification during cell death. It
      involves the addition of the fatty acid myristate to newly exposed N-terminal
      glycines following caspase cleavage. It promotes membrane binding and
      relocalization of functional protein domains released by caspase cleavage during
      apoptosis, or programmed cell death. However, as the requirement of caspase
      cleavage has expanded beyond just cell death, it has become apparent that PTMyr
      may play a role in cell survival, differentiation and now autophagy. Herein, we
      describe how myristoylation may play a role in autophagy with an emphasis on
      PTMyr. 

PMID- 25849921
TI  - How many lives does CLIMP-63 have?
AB  - In 1995, in the Biochemical Society Transactions, Mundy published the first
      review on CLIMP-63 (cytoskeleton-linking membrane protein 63) or CKPA4
      (cytoskeleton-associated protein 4), initially just p63 [1]. Here we review the
      following 20 years of research on this still mysterious protein. CLIMP-63 is a
      type II transmembrane protein, the cytosolic domain of which has the capacity to
      bind microtubules whereas the luminal domain can form homo-oligomeric complexes,
      not only with neighbouring molecules but also, in trans, with CLIMP-63 molecules
      on the other side of the endoplasmic reticulum (ER) lumen, thus promoting the
      formation of ER sheets. CLIMP-63 however also appears to have a life at the cell
      surface where it acts as a ligand-activated receptor. The still rudimentary
      information of how CLIMP-63 fulfills these different roles, what these are
      exactly and how post-translational modifications control them, will be discussed.

PMID- 25849924
TI  - Palmitoylation and palmitoyl-transferases in Plasmodium parasites.
AB  - Protein post-translational modifications (PTM) are commonly used to regulate
      biological processes. Protein S-acylation is an enzymatically regulated
      reversible modification that has been shown to modulate protein localization,
      activity and membrane binding. Proteome-scale discovery on Plasmodium falciparum
      schizonts has revealed a complement of more than 400 palmitoylated proteins,
      including those essential for host invasion and drug resistance. The wide
      regulatory affect on this species is endorsed by the presence of 12 proteins
      containing the conserved DHHC-CRD (DHHC motif within a cysteine-rich domain) that
      is associated with palmitoyl-transferase activity. Genetic interrogation of these
      enzymes in Apicomplexa has revealed essentiality and distinct localization at
      cellular compartments; these features are species specific and are not observed
      in yeast. It is clear that palmitoylation has an elaborate role in Plasmodium
      biology and opens intriguing questions on the functional consequence of this
      group of acylation modifications and how the protein S-acyl transferases (PATs)
      orchestrate molecular events. 

PMID- 25849923
TI  - Fatty acyl donor selectivity in membrane bound O-acyltransferases and communal
      cell fate decision-making.
AB  - The post-translational modification of proteins with lipid moieties confers
      spatial and temporal control of protein function by restricting their subcellular
      distribution or movement in the extracellular milieu. Yet, little is known about
      the significance of lipid selectivity to the activity of proteins targeted for
      such modifications. Membrane bound O-acyl transferases (MBOATs) are a superfamily
      of multipass enzymes that transfer fatty acids on to lipid or protein substrates.
      Three MBOATs constitute a subfamily with secreted signalling molecules for
      substrates, the Wnt, Hedgehog (Hh) and Ghrelin proteins. Given their important
      roles in adult tissue homoeostasis, all three molecules and their respective
      associated acyltransferases provide a framework for interrogating the role of
      extracellular acylation events in cell-to-cell communication. Here, we discuss
      how the preference for a fatty acyl donor in the Wnt acyltransferase porcupine
      (Porcn) and possibly in other protein lipidation enzymes may provide a means for
      coupling metabolic health at the single cell level to communal cell fate decision
      making in complex multicellular organisms. 

PMID- 25849925
TI  - Membrane bound O-acyltransferases and their inhibitors.
AB  - Since the identification of the membrane-bound O-acyltransferase (MBOATs) protein
      family in the early 2000s, three distinct members [porcupine (PORCN), hedgehog
      (Hh) acyltransferase (HHAT) and ghrelin O-acyltransferase (GOAT)] have been shown
      to acylate specific proteins or peptides. In this review, topology determination,
      development of assays to measure enzymatic activities and discovery of small
      molecule inhibitors are compared and discussed for each of these enzymes. 

PMID- 25849926
TI  - Chemical reporters for exploring protein acylation.
AB  - Proteins are acylated by a variety of metabolites that regulates many important
      cellular pathways in all kingdoms of life. Acyl groups in cells can vary in
      structure from the smallest unit, acetate, to modified long-chain fatty acids,
      all of which can be activated and covalently attached to diverse amino acid side
      chains and consequently modulate protein function. For example, acetylation of
      Lys residues can alter the charge state of proteins and generate new recognition
      elements for protein-protein interactions. Alternatively, long-chain fatty
      acylation targets proteins to membranes and enables spatial control of cell
      signalling. To facilitate the analysis of protein acylation in biology, acyl
      analogues bearing alkyne or azide tags have been developed that enable
      fluorescent imaging and proteomic profiling of modified proteins using
      bioorthogonal ligation methods. Herein, we summarize the currently available
      acylation chemical reporters and highlight their utility to discover and quantify
      the roles of protein acylation in biology. 

PMID- 25849927
TI  - Cholesterylation: a tail of hedgehog.
AB  - Cholesterylation is a post-translational attachment of sterol to proteins. This
      modification has been a characteristic of a single family of hedgehog proteins
      (Hh). Hh is a well-established morphogenic molecule important in embryonic
      development. It was also found to be involved in the progression of many cancer
      types. Herein, we describe the mechanism of biosynthesis of cholesterylated Hh,
      the role of this unusual modification on protein functions and novel chemical
      probes, which could be used to specifically target this modification, both in
      vitro and in vivo.

PMID- 25849928
TI  - Activation of the E3 ubiquitin ligase Parkin.
AB  - The PINK1 (phosphatase and tensin homologue-induced putative kinase 1)/Parkin
      dependent mitochondrial quality control pathway mediates the clearance of damaged
      organelles, but appears to be disrupted in Parkinson's disease (PD) [Springer and
      Kahle (2011) Autophagy 7, 266-278]. Upon mitochondrial stress, PINK1 activates
      the E3 ubiquitin (Ub) ligase Parkin through phosphorylation of the Ub-like (UBL)
      domain of Parkin and of the small modifier Ub itself at a conserved residue
      [Sauve and Gehring (2014) Cell Res. 24, 1025-1026]. Recently resolved partial
      crystal structures of Parkin showed a 'closed', auto-inhibited conformation,
      consistent with its notoriously weak enzymatic activity at steady state [Wauer
      and Komander (2013) EMBO J. 32, 2099-2112; Riley et al. (2013) Nat. Commun. 4,
      1982; Trempe et al. (2013) Science 340, 1451-1455; Spratt et al. (2013) Nat.
      Commun. 4, 1983]. It has thus become clear that Parkin must undergo major
      structural rearrangements in order to unleash its catalytic functions. Recent
      published findings derived from X-ray structures and molecular modelling present
      a complete structural model of human Parkin at an all-atom resolution [Caulfield
      et al. (2014) PLoS Comput. Biol. 10, e1003935]. The results of the combined in
      silico simulations-based and experimental assay-based study indicates that PINK1
      dependent Ser65 phosphorylation of Parkin is required for its activation and
      triggering of 'opening' conformations. Indeed, the obtained structures showed a
      sequential release of Parkin's intertwined domains and allowed docking of an Ub
      charged E2 coenzyme, which could enable its enzymatic activity. In addition,
      using cell-based screening, select E2 enzymes that redundantly, cooperatively or
      antagonistically regulate Parkin's activation and/or enzymatic functions at
      different stages of the mitochondrial autophagy (mitophagy) process were
      identified [Fiesel et al. (2014) J. Cell Sci. 127, 3488-3504]. Other work that
      aims to pin-point the particular pathogenic dysfunctions of Parkin mis-sense
      mutations have been recently disseminated (Fabienne C. Fiesel, Thomas R.
      Caulfield, Elisabeth L. Moussaud-Lamodiere, Daniel F.A.R. Dourado, Kotaro Ogaki,
      Owen A. Ross, Samuel C. Flores, and Wolfdieter Springer, submitted). Such a
      structure-function approach provides the basis for the dissection of Parkin's
      regulation and a targeted drug design to identify small-molecule activators of
      this neuroprotective E3 Ub ligase.

PMID- 25849929
TI  - Stimulation of electron transport as potential novel therapy in Parkinson's
      disease with mitochondrial dysfunction.
AB  - Parkinson's disease (PD) is a neurodegenerative motor disorder characterized by
      the loss of dopaminergic neurons. This loss of dopaminergic neurons is the
      pathological hallmark of the disease that results in the characteristic motor
      syndrome. Restoration of dopamine levels is the basis of current therapy;
      however, this does not tackle the cause of the disease. While the aetiology of PD
      remains mostly elusive, mitochondrial dysfunction has been linked to (at least)
      part of the PD cases. In this review we discuss recent findings in Drosophila
      melanogaster showing that stimulation of the electron transport chain is
      beneficial for PD fly models showing Complex I defects and discuss the possible
      clinical applications of these findings. 

PMID- 25849930
TI  - PINK1 activation-turning on a promiscuous kinase.
AB  - PINK1 [phosphatase and tensin homologue (PTEN)-induced putative kinase 1] is a
      serine/threonine kinase targeted to mitochondria and implicated in early-onset
      recessive Parkinson's disease (PD). Through the phosphorylation of its downstream
      targets, PINK1 regulates multiple mitochondrial processes, including ATP
      production, stress-response and mitochondrial dynamics and quality control. The
      orchestration of such a wide array of functions by an individual kinase requires
      a fine-tuned and versatile regulation of its activity. PINK1 proteolytic
      processing, trafficking and localization, as well as different post-translational
      modifications, affect its activity and function. Unravelling the regulatory
      mechanisms of PINK1 is essential for a full comprehension of its kinase function
      in health and disease. 

PMID- 25849931
TI  - Biochemical properties of the kinase PINK1 as sensor protein for mitochondrial
      damage signalling.
AB  - Defects of mitochondrial functions have been implicated in many different human
      diseases, in particular neurodegenerative diseases. The kinase PINK1 [phosphatase
      and tensin homologue (PTEN)-induced kinase 1] has been identified as a crucial
      player in a specific damage signalling pathway, eliminating defective
      mitochondria by an autophagic process. Mutations in PINK1 have been shown to
      cause familial cases of Parkinson's disease. In this review, we summarize the
      biochemical mechanisms that underlie the association of PINK1 with mitochondria
      under normal and pathological conditions. This unconventional mitochondrial
      localization pathway is discussed in the context of the role of PINK1 as a sensor
      of mitochondrial damage and a causative factor in Parkinson's disease.

PMID- 25849932
TI  - Linking microtubules to Parkinson's disease: the case of parkin.
AB  - Microtubules (MTs) are dynamic polymers consisting of alpha/beta tubulin dimers
      and playing a plethora of roles in eukaryotic cells. Looking at neurons, they are
      key determinants of neuronal polarity, axonal transport and synaptic plasticity.
      The concept that MT dysfunction can participate in, and perhaps lead to,
      Parkinson's disease (PD) progression has been suggested by studies using toxin
      based and genetic experimental models of the disease. Here, we first learn
      lessons from MPTP and rotenone as well as from the PD related genes, including
      SNCA and LRRK2, and then look at old and new evidence regarding the interplay
      between parkin and MTs. Data from experimental models and human cells point out
      that parkin regulates MT stability and strengthen the link between MTs and PD
      paving the way to a viable strategy for the management of the disease. 

PMID- 25849933
TI  - The endoplasmic reticulum/mitochondria interface: a subcellular platform for the
      orchestration of the functions of the PINK1-Parkin pathway?
AB  - Mitochondrial dysfunction is a hallmark of both idiopathic and familial
      Parkinson's disease (PD). Mutations in the PARK2 and PARK6 genes, coding for the
      cytosolic E3 ubiquitin protein ligase Parkin and the mitochondrial
      serine/threonine kinase PINK1 [phosphatase and tensin homologue (PTEN)-induced
      putative kinase 1], lead to clinically similar early-onset Parkinsonian
      syndromes. PINK1 and Parkin cooperate within a conserved pathway to preserve
      mitochondrial quality through the regulation of a variety of processes, including
      mitochondrial dynamics, transport, bioenergetics, biogenesis and turnover. The
      molecular mechanisms behind the orchestration of this plethora of functions
      remain poorly understood. In the present review, we emphasize the functional
      overlap between the PINK1-Parkin pathway and the endoplasmic reticulum (ER)
      mitochondria interface, a subcellular compartment critically involved in
      neurodegeneration. We discuss how this compartment may constitute a hub for the
      spatiotemporal organization of the activities of the PINK1-Parkin pathway. 

PMID- 25849934
TI  - iPS models of Parkin and PINK1.
AB  - Parkinson disease (PD) is a degenerative disorder of the central nervous system
      resulting from depletion of dopaminergic neurons and currently remains incurable
      despite enormous international research efforts. The development of induced
      pluripotent stem cell (iPSC) technology opened up the unique possibility of
      studying disease mechanisms in human tissue that was otherwise not accessible,
      such as the brain. Of particular interest are the monogenetic forms of PD as they
      closely resemble the more common 'idiopathic' PD and, through the mutated
      protein, provide a clear research target in iPSC-derived neurons. Recessively
      inherited Parkin and PTEN-induced putative kinase 1 (PINK1) mutations have been
      investigated in this context and the present review describes the first insights
      gained from studies in iPSC-derived dopaminergic neurons, which comprise
      abnormalities in mitochondrial and dopamine homoeostasis, microtubular stability
      and axonal outgrowth. These new models of PD have a high translational potential
      that includes the identification of druggable targets, testing of known and novel
      therapeutic agents in the disease-relevant tissue using well-defined read-outs
      and potential regenerative approaches. 

PMID- 25849935
TI  - GSHSite: exploiting an iteratively statistical method to identify s
      glutathionylation sites with substrate specificity.
AB  - S-glutathionylation, the covalent attachment of a glutathione (GSH) to the sulfur
      atom of cysteine, is a selective and reversible protein post-translational
      modification (PTM) that regulates protein activity, localization, and stability.
      Despite its implication in the regulation of protein functions and cell
      signaling, the substrate specificity of cysteine S-glutathionylation remains
      unknown. Based on a total of 1783 experimentally identified S-glutathionylation
      sites from mouse macrophages, this work presents an informatics investigation on
      S-glutathionylation sites including structural factors such as the flanking amino
      acids composition and the accessible surface area (ASA). TwoSampleLogo presents
      that positively charged amino acids flanking the S-glutathionylated cysteine may
      influence the formation of S-glutathionylation in closed three-dimensional
      environment. A statistical method is further applied to iteratively detect the
      conserved substrate motifs with statistical significance. Support vector machine
      (SVM) is then applied to generate predictive model considering the substrate
      motifs. According to five-fold cross-validation, the SVMs trained with substrate
      motifs could achieve an enhanced sensitivity, specificity, and accuracy, and
      provides a promising performance in an independent test set. The effectiveness of
      the proposed method is demonstrated by the correct identification of previously
      reported S-glutathionylation sites of mouse thioredoxin (TXN) and human protein
      tyrosine phosphatase 1b (PTP1B). Finally, the constructed models are adopted to
      implement an effective web-based tool, named GSHSite
      (http://csb.cse.yzu.edu.tw/GSHSite/), for identifying uncharacterized GSH
      substrate sites on the protein sequences. 

PMID- 25849936
TI  - The amelioration of hepatic steatosis by thyroid hormone receptor agonists is
      insufficient to restore insulin sensitivity in ob/ob mice.
AB  - Thyroid hormone receptor (TR) agonists have been proposed as therapeutic agents
      to treat non-alcoholic fatty liver disease (NAFLD) and insulin resistance. We
      investigated the ability of the TR agonists GC-1 and KB2115 to reduce hepatic
      steatosis in ob/ob mice. Both compounds markedly reduced hepatic triglyceride
      levels and ameliorated hepatic steatosis. However, the amelioration of fatty
      liver was not sufficient to improve insulin sensitivity in these mice and
      reductions in hepatic triglycerides did not correlate with improvements in
      insulin sensitivity or glycemic control. Instead, the effects of TR activation on
      glycemia varied widely and were found to depend upon the time of treatment as
      well as the compound and dosage used. Lower doses of GC-1 were found to further
      impair glycemic control, while a higher dose of the same compound resulted in
      substantially improved glucose tolerance and insulin sensitivity, despite all
      doses being equally effective at reducing hepatic triglyceride levels.
      Improvements in glycemic control and insulin sensitivity were observed only in
      treatments that also increased body temperature, suggesting that the induction of
      thermogenesis may play a role in mediating these beneficial effects. These data
      illustrate that the relationship between TR activation and insulin sensitivity is
      complex and suggests that although TR agonists may have value in treating NAFLD,
      their effect on insulin sensitivity must also be considered. 

PMID- 25849937
TI  - Structural variation discovery in the cancer genome using next generation
      sequencing: computational solutions and perspectives.
AB  - Somatic Structural Variations (SVs) are a complex collection of chromosomal
      mutations that could directly contribute to carcinogenesis. Next Generation
      Sequencing (NGS) technology has emerged as the primary means of interrogating the
      SVs of the cancer genome in recent investigations. Sophisticated computational
      methods are required to accurately identify the SV events and delineate their
      breakpoints from the massive amounts of reads generated by a NGS experiment. In
      this review, we provide an overview of current analytic tools used for SV
      detection in NGS-based cancer studies. We summarize the features of common SV
      groups and the primary types of NGS signatures that can be used in SV detection
      methods. We discuss the principles and key similarities and differences of
      existing computational programs and comment on unresolved issues related to this
      research field. The aim of this article is to provide a practical guide of
      relevant concepts, computational methods, software tools and important factors
      for analyzing and interpreting NGS data for the detection of SVs in the cancer
      genome. 

PMID- 25849938
TI  - Inhibition of BET bromodomains as a therapeutic strategy for cancer drug
      discovery.
AB  - As a conserved protein interaction module that recognizes and binds to acetylated
      lysine, bromodomain (BRD) contains a deep, largely hydrophobic acetyl lysine
      binding site. Proteins that share the feature of containing two BRDs and an extra
      terminal domain belong to BET family, including BRD2, BRD3, BRD4 and BRDT. BET
      family proteins perform transcription regulatory function under normal
      conditions, while in cancer, they regulate transcription of several oncogenes,
      such as c-Myc and Bcl-2. Thus, targeting BET proteins may be a promising
      strategy, and intense interest of BET proteins has fueled the development of
      structure-based bromodomain inhibitors in cancer. In this review, we focus on
      summarizing several small-molecule BET inhibitors and their relevant anti-tumor
      mechanisms, which would provide a clue for exploiting new targeted BET inhibitors
      in the future cancer therapy. 

PMID- 25849939
TI  - Combination of carbon ion beam and gemcitabine causes irreparable DNA damage and
      death of radioresistant pancreatic cancer stem-like cells in vitro and in vivo.
AB  - We try to elucidate whether a carbon ion beam alone or in combination with
      gemcitabine has advantages over X-ray in targeting putative pancreatic cancer
      stem-like cells (CSCs) in vitro and in vivo. Colony, spheroid formation and
      tumorigenicity assays confirmed that CD44+/ESA+ cells sorted from PANC1 and PK45
      cells have more CSC properties than CD44-/ESA- cells. The number of colonies and
      spheroids formed from CSCs after carbon ion beam irradiation was significantly
      reduced compared to after X-ray irradiation, and they were extremely highly
      suppressed when carbon ion beam combined with gemcitabine. The relative
      biological effectiveness (RBE) values for the carbon ion beam relative to X-ray
      at the D10 levels for CSCs were 2.23-2.66. Expressions of multiple cell death
      related genes were remarkably highly induced, and large numbers of gammaH2AX foci
      in CSCs were formed after carbon ion beam combined with gemcitabine. The highly
      expressed CSC markers were significantly inhibited after 30 Gy of carbon ion beam
      and almost lost after 25 Gy carbon ion beam combined with 50 mg/kg gemcitabine.
      In conclusion, a carbon ion beam combined with gemcitabine has superior potential
      to kill pancreatic CSCs via irreparable clustered DSB compared to a carbon ion
      alone or X-rays combined with gemcitabine. 

PMID- 25849940
TI  - Clostridium novyi-NT can cause regression of orthotopically implanted
      glioblastomas in rats.
AB  - Glioblastoma (GBM) is a highly aggressive primary brain tumor that is especially
      difficult to treat. The tumor's ability to withstand hypoxia leads to enhanced
      cancer cell survival and therapy resistance, but also yields a microenvironment
      that is in many aspects unique within the human body, thus offering potential
      therapeutic opportunities. The spore-forming anaerobic bacterium Clostridium
      novyi-NT(C. novyi-NT) has the ability to propagate in tumor-generated hypoxia,
      leading to oncolysis. Here, we show that intravenously injected spores of C.
      novyi-NT led to dramatic tumor destructions and significant survival increases in
      implanted, intracranial syngeneic F98 and human xenograft 060919 rat GBM models.
      C. novyi-NT germination was specific and confined to the neoplasm, with sparing
      of the normal brain parenchyma. All animals tolerated the bacteriolytic
      treatment, but edema and increased intracranial pressure could quickly be lethal
      if not monitored and medically managed with hydration and antibiotics. These
      results provide pre-clinical data supporting the development of this therapeutic
      approach for the treatment of patients with GBM. 

PMID- 25849941
TI  - Transforming growth factor-beta pathway activity in glioblastoma.
AB  - Transforming growth factor (TGF)-beta is a central molecule maintaining the
      malignant phenotype of glioblastoma. Anti-TGF-beta strategies are currently being
      explored in early clinical trials. Yet, there is little contemporary data on the
      differential expression of TGF-beta isoforms at the mRNA and protein level or TGF
      beta/Smad pathway activity in glioblastomas in vivo.Here we studied 64 newly
      diagnosed and 16 recurrent glioblastomas for the expression of TGF-beta1-3,
      platelet-derived growth factor (PDGF)-B, and plasminogen activator inhibitor
      (PAI)-1 mRNA by RT-PCR and for the levels of TGF-beta1-3 protein, phosphorylated
      Smad2 (pSmad2), pSmad1/5/8 and PAI-1 by immunohistochemistry.Among the TGF-beta
      isoforms, TGF-beta1 mRNA was the most, whereas TGF-beta3 mRNA was the least
      abundant. TGF-beta1-3 mRNA expression was strongly correlated, as was the
      expression of TGF-beta1-3 mRNA, and of the TGF-beta1-3 target genes, PDGF-B and
      PAI-1. TGF-beta2 and TGF-beta3 protein levels correlated well, whereas the
      comparison of the other TGF-betaisoforms did not. Positive correlation was also
      observed between TGF-beta1 and pSmad1/5/8 and between pSmad2 and pSmad1/5/8.
      Survival analyses indicated that a group of patients with high expression levels
      of TGF-beta2 mRNA or pSmad1/5/8 protein have inferior outcome.We thus provide
      potential biomarkers for patient stratification in clinical trials of anti-TGF
      beta therapies in glioblastoma. 

PMID- 25849942
TI  - Cyclooxygenase-2 blockade can improve efficacy of VEGF-targeting drugs.
AB  - Anti-angiogenic therapies were approved for different cancers. However,
      significant primary and secondary resistance hampers efficacy in several tumor
      types including breast cancer. Thus, we need to develop clinically applicable
      strategies to enhance efficacy of anti-angiogenic drugs.We report that anti
      angiogenic therapies can induce upregulation of cyclooxygenase-2 (Cox-2) and of
      its product prostaglandin E2 (PGE2) in breast cancer models. Upon Cox-2
      inhibition PGE2 levels were normalized and efficacy of anti-vascular endothelial
      growth factor receptor 2 (anti-VEGFR-2) antibodies and sunitinib was enhanced.
      Interestingly, both treatments exerted additive anti-angiogenic effects.
      Following Cox-2 inhibition, we observed reduced infiltration of tumors with
      cancer-associated fibroblasts (CAFs) and lower levels of pro-angiogenic factors
      active besides the VEGF axis including hepatocyte growth factor (HGF) and basic
      fibroblast growth factor (FGF2). Mechanistic studies indicated that Cox-2
      inhibition reduced PGE2-induced migration and proliferation of CAFs via
      inhibiting phosphorylation of Akt.Hence, Cox-2 inhibition can increase efficacy
      of anti-angiogenic treatments and our findings might pave the road for clinical
      investigations of concomitant blockade of Cox-2 and VEGF-signaling. 

PMID- 25849943
TI  - MicroRNA-3127 promotes cell proliferation and tumorigenicity in hepatocellular
      carcinoma by disrupting of PI3K/AKT negative regulation.
AB  - Recent studies have shown that multiple phosphatases deactivate the PI3K/AKT
      signaling pathway. Here we demonstrated that, by suppressing multiple
      phosphatases, miR-3127 promotes growth of hepatocellular carcinoma (HCC). Our
      study also reveals clinical significance of miR-3127 expression in HCC patients.
      MiR-3127 expression was markedly upregulated in HCC tissues and cells.
      Furthermore, high miR-3127 expression was associated with an aggressive phenotype
      and poor prognosis. MiR-3127 overexpression promoted HCC cell proliferation in
      vitro and tumor growth in vivo. Also, miR-3127 accelerated G1-S transition by
      activating AKT/ FOXO1 signaling, by directly targeting the 3' untranslated
      regions (3'UTR) of pleckstrin homology domain leucine-rich repeat protein
      phosphatase 1/2 (PHLPP1/2), inositol polyphosphate phosphatase 4A (INPP4A), and
      inositol polyphosphate-5-phosphatase J (INPP5J) mRNA, repressing their
      expression. In agreement, the miRNA antagonist antagomir-3127 suppressed HCC cell
      proliferation and tumor growth by inhibiting the AKT/FOXO1 signaling. Taken
      together, these findings suggest that silencing miR-3127 might be a potential
      therapeutic strategy. 

PMID- 25849944
TI  - Chronic iron deficiency as an emerging risk factor for osteoporosis: a
      hypothesis.
AB  - Iron is essential in oxygen transport and participates in many enzymatic systems
      in the body, with important roles in collagen synthesis and vitamin D metabolism.
      The relationship between iron and bone health comes from clinical observations in
      iron overload patients who suffered bone loss. The opposite scenario--whether
      iron deficiency, with or without anemia, affects bone metabolism--has not been
      fully addressed. This is of great interest, as this nutrient deficiency is a
      worldwide public health problem and at the same time osteoporosis and bone
      alterations are highly prevalent. This review presents current knowledge on
      nutritional iron deficiency and bone remodeling, the biomarkers to evaluate iron
      status and bone formation and resorption, and the link between iron and bone
      metabolism. Finally, it is hypothesized that chronic iron deficiency induces bone
      resorption and risk of osteoporosis, thus complete recovery from anemia and its
      prevention should be promoted in order to improve quality of life including bone
      health. Several mechanisms are suggested; hence, further investigation on the
      possible impact of chronic iron deficiency on the development of osteoporosis is
      needed.

PMID- 25849945
TI  - Estimated daily intake and seasonal food sources of quercetin in Japan.
AB  - Quercetin is a promising food component, which can prevent lifestyle related
      diseases. To understand the dietary intake of quercetin in the subjects of a
      population-based cohort study and in the Japanese population, we first determined
      the quercetin content in foods available in the market during June and July in or
      near a town in Hokkaido, Japan. Red leaf lettuce, asparagus, and onions contained
      high amounts of quercetin derivatives. We then estimated the daily quercetin
      intake by 570 residents aged 20-92 years old in the town using a food frequency
      questionnaire (FFQ). The average and median quercetin intakes were 16.2 and 15.5
      mg day(-1), respectively. The quercetin intakes by men were lower than those by
      women; the quercetin intakes showed a low correlation with age in both men and
      women. The estimated quercetin intake was similar during summer and winter.
      Quercetin was mainly ingested from onions and green tea, both in summer and in
      winter. Vegetables, such as asparagus, green pepper, tomatoes, and red leaf
      lettuce, were good sources of quercetin in summer. Our results will help to
      elucidate the association between quercetin intake and risks of lifestyle-related
      diseases by further prospective cohort study and establish healthy dietary
      requirements with the consumption of more physiologically useful components from
      foods.

PMID- 25849946
TI  - Unique features of high-density lipoproteins in the Japanese: in population and
      in genetic factors.
AB  - Despite its gradual increase in the past several decades, the prevalence of
      atherosclerotic vascular disease is low in Japan. This is largely attributed to
      difference in lifestyle, especially food and dietary habits, and it may be
      reflected in certain clinical parameters. Plasma high-density lipoprotein (HDL)
      levels, a strong counter risk for atherosclerosis, are indeed high among the
      Japanese. Accordingly, lower HDL seems to contribute more to the development of
      coronary heart disease (CHD) than an increase in non-HDL lipoproteins at a
      population level in Japan. Interestingly, average HDL levels in Japan have
      increased further in the past two decades, and are markedly higher than in
      Western populations. The reasons and consequences for public health of this
      increase are still unknown. Simulation for the efficacy of raising HDL
      cholesterol predicts a decrease in CHD of 70% in Japan, greater than the extent
      by reducing low-density lipoprotein cholesterol predicted by simulation or
      achieved in a statin trial. On the other hand, a substantial portion of
      hyperalphalipoproteinemic population in Japan is accounted for by genetic
      deficiency of cholesteryl ester transfer protein (CETP), which is also commonly
      unique in East Asian populations. It is still controversial whether CETP
      mutations are antiatherogenic. Hepatic Schistosomiasis is proposed as a potential
      screening factor for historic accumulation of CETP deficiency in East Asia. 

PMID- 25849947
TI  - Maternal dietary patterns during pregnancy in relation to offspring forearm
      fractures: prospective study from the Danish National Birth Cohort.
AB  - Limited evidence exists for an association between maternal diet during pregnancy
      and offspring bone health. In a prospective study, we examined the association
      between dietary patterns in mid-pregnancy and offspring forearm fractures. In
      total, 101,042 pregnancies were recruited to the Danish National Birth Cohort
      (DNBC) during 1996-2002. Maternal diet was collected by a food frequency
      questionnaire. Associations were analyzed between seven dietary patterns
      extracted by principal component analysis and offspring first occurrence of any
      forearm fracture diagnosis, extracted from the Danish National Patient Register,
      between time of birth and end of follow-up (< 16 year) (n = 53,922). In
      multivariable Cox regression models, offspring of mothers in the fourth vs. first
      quintile of the Western pattern had a significant increased risk (Hazard ratio,
      95% confidence interval: 1.11, 1.01-1.23) of fractures, and there was a
      borderline significant positive trend (p = 0.06). The other dietary patterns
      showed no associations and neither did supplementary analyses of macro- and
      micronutrients or single food groups, except for the intake of artificially
      sweetened soft drinks, which was positively associated with offspring forearm
      fractures (p = 0.02). In the large prospective DNBC high mid-pregnancy
      consumption of Western diet and artificially sweetened soft drinks, respectively,
      indicated positive associations with offspring forearm fractures, which provides
      interesting hypotheses for future research.

PMID- 25849948
TI  - Low maternal vitamin B12 status is associated with lower cord blood HDL
      cholesterol in white Caucasians living in the UK.
AB  - BACKGROUND AND AIMS: Studies in South Asian population show that low maternal
      vitamin B12 associates with insulin resistance and small for gestational age in
      the offspring. Low vitamin B12 status is attributed to vegetarianism in these
      populations. It is not known whether low B12 status is associated with metabolic
      risk of the offspring in whites, where the childhood metabolic disorders are
      increasing rapidly. Here, we studied whether maternal B12 levels associate with
      metabolic risk of the offspring at birth. METHODS: This is a cross-sectional
      study of 91 mother-infant pairs (n = 182), of white Caucasian origin living in
      the UK. Blood samples were collected from white pregnant women at delivery and
      their newborns (cord blood). Serum vitamin B12, folate, homocysteine as well as
      the relevant metabolic risk factors were measured. RESULTS: The prevalence of low
      serum vitamin B12 (<191 ng/L) and folate (<4.6 MUg/L) were 40% and 11%,
      respectively. Maternal B12 was inversely associated with offspring's Homeostasis
      Model Assessment 2-Insulin Resistance (HOMA-IR), triglycerides, homocysteine and
      positively with HDL-cholesterol after adjusting for age and BMI. In regression
      analysis, after adjusting for likely confounders, maternal B12 is independently
      associated with neonatal HDL-cholesterol and homocysteine but not triglycerides
      or HOMA-IR. CONCLUSIONS: Our study shows that low B12 status is common in white
      women and is independently associated with adverse cord blood cholesterol.

PMID- 25849949
TI  - Role of dietary protein and thiamine intakes on cognitive function in healthy
      older people: a systematic review.
AB  - The effectiveness of nutritional interventions to prevent and maintain cognitive
      functioning in older adults has been gaining interest due to global population
      ageing. A systematic literature review was conducted to obtain and appraise
      relevant studies on the effects of dietary protein or thiamine on cognitive
      function in healthy older adults. Studies that reported on the use of nutritional
      supplementations and/or populations with significant cognitive impairment were
      excluded. Seventeen eligible studies were included. Evidence supporting an
      association between higher protein and/or thiamine intakes and better cognitive
      function is weak. There was no evidence to support the role of specific protein
      food sources, such as types of meat, on cognitive function. Some cross-sectional
      and case-control studies reported better cognition in those with higher dietary
      thiamine intakes, but the data remains inconclusive. Adequate protein and
      thiamine intake is more likely associated with achieving a good overall
      nutritional status which affects cognitive function rather than single nutrients.
      A lack of experimental studies in this area prevents the translation of these
      dietary messages for optimal cognitive functioning and delaying the decline in
      cognition with advancing age. 

PMID- 25849950
TI  - Hepatoprotective effect of herb formula KIOM2012H against nonalcoholic fatty
      liver disease.
AB  - Nonalcoholic fatty liver disease (NAFLD) is a hepatic ailment with a rapidly
      increasing incidence due to dietary hypernutrition and subsequent obesity. Fatty
      liver disease can lead to steatohepatitis, fibrosis, cirrhosis, and even cancer,
      which is associated with various complications. Discovering effective natural
      materials and herbs can provide alternative and complementary medical treatments
      to current chemical pharmaceuticals. To develop an effective natural agent for
      NAFLD, we formulated a combination of four herb mixtures (KIOM2012H) and observed
      lipid-lowering efficacy. The inhibitory effects of KIOM2012H on free fatty acid
      induced lipid accumulation, triglyceride contents, and gene expressions were
      analyzed in HepG2 cells. Using high fat diet-fed mice, body weight changes, gross
      liver appearances, hepatic triglyceride contents, and gene expressions were
      evaluated. KIOM2012H dose-dependently inhibited lipid accumulation and gene
      expressions involved in lipogenesis and related regulators. Experimental animals
      also showed a decrease in body weight changes and lipid-associated physiological
      parameters. This study shows that KIOM2012H has an alleviating effect on fatty
      acid and lipid accumulation, and therefore can be applied for development of new
      therapeutic pharmaceuticals for treatment of NAFLD using natural products and
      herbs. 

PMID- 25849951
TI  - Atorvastatin reduces long pentraxin 3 expression in vascular cells by inhibiting
      protein geranylgeranylation.
AB  - BACKGROUND: The long pentraxin PTX3 is an acute-phase multi-functional protein
      that might play both positive and detrimental effects under different
      pathophysiological conditions. We previously showed that statins down-regulate
      the release of PTX3 in human endothelial cells (ECs). The present study
      investigated the mechanism mediating this effect, its occurrence in other cells
      involved in atherogenesis, and whether it takes place in experimental
      atherosclerosis. METHODS AND RESULTS: We found that atorvastatin (1-5 MUmol/L)
      decreased the production and release of PTX3 in human ECs through a post
      transcriptional effect. Co-incubation with mevalonate or geranylgeranyl
      pyrophosphate prevented this effect. Direct blockade of geranylgeranyl
      transferase I by GGTI-286, treatment with the Rac inhibitor NSC23766 or silencing
      of the geranylgeranylated GTPase Rac2 by siRNA closely mimicked the action of
      atorvastatin. In contrast, inactivation of other geranylgeranylated proteins such
      as RhoA, RhoB, and RhoC or Rac1 did not affect PTX3 release. In addition, we
      found that atorvastatin also decreased PTX3 secretion in aortic SMCs through a
      mechanism likely dependent on protein geranylgeranylation, while no effect was
      observed in monocytes. Finally, we found that atherosclerotic lesions from
      cholesterol-fed rabbits treated with atorvastatin (2.5 mg/kg/day for 8 weeks)
      showed less immunoreactive PTX3 than lesions from control animals. CONCLUSIONS:
      Results suggest that statins may interfere with PTX3 expression in vascular cells
      via inhibition of protein geranylgeranylation. Since PTX3 is increasingly
      regarded as an important mediator of the inflammatory response underlying
      atherosclerosis and its complications, these results highlight the need for
      further studies of the role of PTX3 and its potential pharmacological modulation
      in cardiovascular disease.

PMID- 25849953
TI  - Photochemical activation of drugs for the treatment of therapy-resistant cancers.
AB  - Resistance to chemotherapy, molecular targeted therapy as well as radiation
      therapy is a major obstacle for cancer treatment. Cancer resistance may be
      exerted through multiple different mechanisms which may be orchestrated as
      observed in multidrug resistance (MDR). Cancer resistance may be intrinsic or
      acquired and often leaves patients without any treatment options. Strategies for
      alternative treatment modalities for resistant cancer are therefore highly
      warranted. Photochemical internalization (PCI) is a technology for cytosolic
      delivery of macromolecular therapeutics based on the principles of photodynamic
      therapy (PDT). The present report reviews the current knowledge of PCI of therapy
      resistant cancers. In summary, PCI may be able to circumvent several of the major
      mechanisms associated with resistance towards chemotherapeutics including
      increased expression of drug efflux pumps, altered intracellular drug
      distribution and increased ROS scavenging. Current data also suggest PCI of
      targeted toxins as highly effective in cancers resistant to clinically available
      targeted therapy such as monoclonal antibodies (mAbs) and tyrosine kinase
      inhibitors (TKIs). PCI may therefore, in general, represent a future treatment
      option for cancers resistant to other therapies. 

PMID- 25849952
TI  - Myricitrin attenuates endothelial cell apoptosis to prevent atherosclerosis: An
      insight into PI3K/Akt activation and STAT3 signaling pathways.
AB  - Blood vessel endothelial dysfunction induced by oxidized low-density lipoprotein
      (ox-LDL) has been implicated in the pathogenesis of atherosclerosis and
      vasculopathy. The ox-LDL-elicited reactive oxygen species (ROS) release has been
      assumed to serve a critical function in endothelial damage. Myricitrin (from
      Myrica cerifera) is a natural antioxidant that has strong anti-oxidative, anti
      inflammatory, and anti-nociceptive activities. However, the protective effect of
      myricitrin on ROS-induced endothelial cell injury and its related molecular
      mechanisms have never been investigated. This study demonstrates that myricitrin
      can inhibit ox-LDL-induced endothelial apoptosis and prevent plaque formation at
      an early stage in an atherosclerotic mouse model. The administration of
      myricitrin in vivo decreases the thickness of the vascular wall in the aortic
      arch of ApoE-/- mice. In vitro study shows that ox-LDL-induced human umbilical
      vein endothelial cell apoptosis can be reduced upon receiving myricitrin pre
      treatment. Treatment with myricitrin significantly attenuated ox-LDL-induced
      endothelial cell apoptosis by inhibiting LOX-1 expression and by increasing the
      activation of the STAT3 and PI3K/Akt/eNOS signaling pathways. At the same time,
      our result demonstrates that myricitrin treatment optimizes the balance of
      pro/anti-apoptosis proteins, including Bax, Bad, XIAP, cIAP-2, and survivin. Our
      study suggests that myricitrin treatment can effectively protect cells from ox
      LDL-induced endothelial cell apoptosis, which results in reduced atherosclerotic
      plaque formation. This result indicates that myricitrin can be used as a drug
      candidate for the treatment of cardiovascular diseases. 

PMID- 25849954
TI  - Microarray analysis identifies IL-1 receptor type 2 as a novel candidate
      biomarker in patients with acute respiratory distress syndrome.
AB  - BACKGROUND: Acute respiratory distress syndrome (ARDS) is a disease associated
      with a high mortality rate. The initial phase is characterized by induction of
      inflammatory cytokines and chemokines and influx of circulating inflammatory
      cells, including macrophages which play a pivotal role in the innate and adaptive
      immune responses to injury. Growing evidence points to phenotypic heterogeneity
      and plasticity between various macrophage activation states. METHODS: In this
      study, gene expression in alveolar macrophages and circulating leukocytes from
      healthy control subjects and patients with ARDS was assessed by mRNA microarray
      analysis. RESULTS: Both alveolar macrophages and circulating leukocytes
      demonstrated up-regulation of genes encoding chemotactic factors, antimicrobial
      peptides, chemokine receptors, and matrix metalloproteinases. Two genes, the pro
      inflammatory S100A12 and the anti-inflammatory IL-1 decoy receptor IL-1R2 were
      significantly induced in both cell populations in ARDS patients, which was
      confirmed by protein quantification. Although S100A12 levels did not correlate
      with disease severity, there was a significant association between early plasma
      levels of IL-1R2 and APACHE III scores at presentation. Moreover, higher levels
      of IL-1R2 in plasma were observed in non-survivors as compared to survivors at
      later stages of ARDS. CONCLUSIONS: These results suggest a hybrid state of
      alveolar macrophage activation in ARDS, with features of both alternative
      activation and immune tolerance/deactivation.. Furthermore, we have identified a
      novel plasma biomarker candidate in ARDS that correlates with the severity of
      systemic illness and mortality.

PMID- 25849955
TI  - Enhancement of reproductive heat tolerance in plants.
AB  - Comparison of average crop yields with reported record yields has shown that
      major crops exhibit annual average yields three- to seven-fold lower than record
      yields because of unfavorable environments. The current study investigated the
      enhancement of pollen heat tolerance through expressing an Arabidopsis thaliana
      heat shock protein 101 (AtHSP101) that is not normally expressed in pollen but
      reported to play a crucial role in vegetative thermotolerance. The AtHSP101
      construct under the control of the constitutive ocs/mas 'superpromoter' was
      transformed into cotton Coker 312 and tobacco SRI lines via Agrobacterium
      mediated transformation. Thermotolerance of pollen was evaluated by in vitro
      pollen germination studies. Comparing with those of wild type and transgenic null
      lines, pollen from AtHSP101 transgenic tobacco and cotton lines exhibited
      significantly higher germination rate and much greater pollen tube elongation
      under elevated temperatures or after a heat exposure. In addition, significant
      increases in boll set and seed numbers were also observed in transgenic cotton
      lines exposed to elevated day and night temperatures in both greenhouse and field
      studies. The results of this study suggest that enhancing heat tolerance of
      reproductive tissues in plant holds promise in the development of crops with
      improved yield production and yield sustainability in unfavorable environments. 

PMID- 25849956
TI  - Inclined to see it your way: Do altercentric intrusion effects in visual
      perspective taking reflect an intrinsically social process?
AB  - It has been suggested that some aspects of mental state understanding recruit a
      rudimentary, but fast and efficient, processing system, demonstrated by the
      obligatory slowing down of judgements about what the self can see when this is
      incongruent with what another can see. We tested the social nature of this system
      by investigating to what extent these altercentric intrusions are elicited under
      conditions that differed in their social relevance and, further, how these
      related to self-reported social perspective taking and empathy. In Experiment 1,
      adult participants were asked to make "self" or "other" perspective-taking
      judgements during congruent ("self" and "other" can see the same items) or
      incongruent conditions ("self" and "other" cannot see the same items) in
      conditions that were social (i.e., involving a social agent), semisocial (an
      arrow), or nonsocial (a dual-coloured block). Reaction time indices of
      altercentric intrusion effects were present across all conditions, but were
      significantly stronger for the social than for the less social conditions. Self
      reported perspective taking and empathy correlated with altercentric intrusion
      effects in the social condition only. In Experiment 2, the significant
      correlations for the social condition were replicated, but this time with gaze
      duration indices of altercentric intrusion effects. Findings are discussed with
      regard to the degree to which this rudimentary system is socially specialized and
      how it is linked to more conceptual understanding. 

PMID- 25849957
TI  - Second German-Catalan workshop on epigenetics & cancer.
AB  - The Second German-Catalan Workshop on Epigenetics and Cancer was held in
      Barcelona on November 19-21, 2014. The workshop brought together, for the second
      time, scientists from 2 German and 2 Catalan research institutions: the DKFZ,
      from Heidelberg, the CRCME, from Freiburg, and the IMPPC and PEBC/IDIBELL, both
      from Barcelona. The German-Catalan Workshops are intended to establish the
      framework for building a Research School to foster collaborations between
      researchers from the different institutions. Exchange programs for graduate
      students are among the activities of the future School. The topics presented and
      discussed in 33 talks were diverse and included work on DNA methylation, histone
      modifications, chromatin biology, characterization of imprinted regions in human
      tissues, non-coding RNAs, and epigenetic drug discovery. Among novel developments
      from the previous Workshop are the report of the epigenetics angle of the Warburg
      effect and the long-range trans-acting interaction of DNA methylation and of
      nucleosome remodeling. A shift in the view on DNA methylation became apparent by
      the realization of the intertwined interplay between hyper- and hypo-methylation
      in differentiation and cancer. 

PMID- 25849958
TI  - Asymmetry of deep medullary veins on susceptibility weighted MRI in patients with
      acute MCA stroke is associated with poor outcome.
AB  - BACKGROUND AND PURPOSE: Due to its sensitivity to deoxyhemoglobin, susceptibility
      weighted imaging (SWI) enables the visualization of deep medullary veins (DMV) in
      patients with acute stroke, which are difficult to depict under physiological
      circumstances. This study assesses the asymmetric appearance of prominent DMV as
      an independent predictor for stroke severity and outcome. MATERIALS AND METHODS:
      SWI of 86 patients with acute middle cerebral artery (MCA) stroke were included.
      A scoring system from 0 (no visible DMV) to 3 (very prominent DMV) was applied
      for both hemispheres separately. A difference of scores between ipsi- and
      contralateral side was defined as asymmetric (AMV+). Occurrence of AMV+ was
      correlated with the National Institute of Health Stroke Scale (NIHSS) Score on
      admission and discharge, as well as the modified Rankin Scale (mRS) at discharge.
      Ordinal regression analysis was used to evaluate NIHSS and mRS as predictors of
      stroke severity, clinical course of disease and outcome. RESULTS: 55 patients
      displayed AMV+ while 31 did not show an asymmetry (AMV-). Median NIHSS on
      admission was 17 (11-21) in the AMV+ group and 9 (5-15) in the AMV- group (p =
      0.001). On discharge median NIHSS was 11 (5-20) for AMV+ and 5 (2-14) for AMV- (p
      = 0.005). The median mRS at discharge was 4 (3-5) in the AMV+ group and 3 (1-4)
      in AMV- (p = 0.001). Odds ratio was 3.19 (95% CI: 1.24-8.21) for AMV+ to achieve
      a higher mRS than AMV- (p = 0.016). CONCLUSION: The asymmetric appearance of DMV
      on SWI is a fast and easily evaluable parameter for the prediction of stroke
      severity and can be used as an additional imaging parameter in patients with
      acute MCA stroke.

PMID- 25849959
TI  - Assessing species boundaries using multilocus species delimitation in a
      morphologically conserved group of neotropical freshwater fishes, the Poecilia
      sphenops species complex (Poeciliidae).
AB  - Accurately delimiting species is fundamentally important for understanding
      species diversity and distributions and devising effective strategies to conserve
      biodiversity. However, species delimitation is problematic in many taxa,
      including 'non-adaptive radiations' containing morphologically cryptic lineages.
      Fortunately, coalescent-based species delimitation methods hold promise for
      objectively estimating species limits in such radiations, using multilocus
      genetic data. Using coalescent-based approaches, we delimit species and infer
      evolutionary relationships in a morphologically conserved group of Central
      American freshwater fishes, the Poecilia sphenops species complex. Phylogenetic
      analyses of multiple genetic markers (sequences of two mitochondrial DNA genes
      and five nuclear loci) from 10/15 species and genetic lineages recognized in the
      group support the P. sphenops species complex as monophyletic with respect to
      outgroups, with eight mitochondrial 'major-lineages' diverged by >=2% pairwise
      genetic distances. From general mixed Yule-coalescent models, we discovered
      (conservatively) 10 species within our concatenated mitochondrial DNA dataset, 9
      of which were strongly supported by subsequent multilocus Bayesian species
      delimitation and species tree analyses. Results suggested species-level diversity
      is underestimated or overestimated by at least ~15% in different lineages in the
      complex. Nonparametric statistics and coalescent simulations indicate
      genealogical discordance among our gene tree results has mainly derived from
      interspecific hybridization in the nuclear genome. However, mitochondrial DNA
      show little evidence for introgression, and our species delimitation results
      appear robust to effects of this process. Overall, our findings support the
      utility of combining multiple lines of genetic evidence and broad
      phylogeographical sampling to discover and validate species using coalescent
      based methods. Our study also highlights the importance of testing for
      hybridization versus incomplete lineage sorting, which aids inference of not only
      species limits but also evolutionary processes influencing genetic diversity. 

PMID- 25849960
TI  - Mortality related to acute illness and injury in rural Uganda: task shifting to
      improve outcomes.
AB  - BACKGROUND: Due to the dual critical shortages of acute care and healthcare
      workers in resource-limited settings, many people suffer or die from conditions
      that could be easily treated if existing resources were used in a more timely and
      effective manner. In order to address this preventable morbidity and mortality, a
      novel emergency midlevel provider training program was developed in rural Uganda.
      This is the first study that assesses this unique application of a task-shifting
      model to acute care by evaluating the outcomes of 10,105 patients. METHODS:
      Nurses participated in a two-year training program to become midlevel providers
      called Emergency Care Practitioners at a rural district hospital. This is a
      retrospective analysis of the Emergency Department's quality assurance database,
      including three-day follow-up data. Case fatality rates (CFRs) are reported as
      the percentage of cases with a specific diagnosis that died within three days of
      their Emergency Department visit. FINDINGS: Overall, three-day mortality was
      2.0%. The most common diagnoses of patients who died were malaria (n=60),
      pneumonia (n=51), malnutrition (n=21), and trauma (n=18). Overall and under-five
      CFRs were as follows: malaria, 2.0% and 1.9%; pneumonia, 5.5% and 4.1%; and
      trauma, 1.2% and 1.6%. Malnutrition-related fatality (all cases <18 years old)
      was 6.5% overall and 6.8% for under-fives. INTERPRETATION: This study describes
      the outcomes of emergency patients treated by midlevel providers in a resource
      limited setting. Our fatality rates are lower than previously published regional
      rates. These findings suggest this model of task-shifting can be successfully
      applied to acute care in order to address the shortage of emergency care services
      in similar settings as part of an integrated approach to health systems
      strengthening.

PMID- 25849961
TI  - Recurrence After Primary Pterygium Excision: Amniotic Membrane Transplantation
      with Fibrin Glue Versus Conjunctival Autograft with Fibrin Glue.
AB  - PURPOSE: The aim of the present study was to compare the surgical results and
      recurrence rates of primary pterygium excision with conjunctival autografts
      versus amniotic membrane grafts fixated with fibrin glue. MATERIALS AND METHODS:
      In this prospective study, 73 eyes of 65 patients who had undergone conjunctival
      autograft group (CAG) (n:37) or amniotic membrane group (AMG) (n:36) after
      pterygium excision were evaluated. Fibrin glue was used for the fixation of
      grafts in both groups. The patients were followed up for 12 months. Postoperative
      complications were recorded. The rate of recurrence was defined as the primary
      outcome measure. RESULTS: In the CAG, partial dehiscence of the graft was
      observed on the nasal edge on postoperative day 1 in two (5.4%) eyes that healed
      with secondary re-epithelialization at week 1. Twelve (32.4%) eyes showed a
      yellowish-orange or hemorrhagic edema of the graft on postoperative day 7 that
      spontaneously resolved in 1 to 3 weeks. In the AMG, partial dehiscence and
      folding of the amniotic membrane occurred in two (5.5%) eyes. Two eyes (5.4 %) in
      the CAG developed corneal recurrence and five eyes (13.8%) in the amniotic
      membrane graft group developed recurrence; one limbal (2.7%), four corneal
      recurrences (11.1%) (p = 0.25). CONCLUSION: Fibrin glue is a safe and effective
      method for attaching conjunctival or amniotic membrane grafts for wound closure
      following pterygium surgery. Although the results were not statistically
      significant, amniotic membrane grafting using fibrin glue seems to have a higher
      pterygium recurrence rate compared with conjunctival autografting.

PMID- 25849962
TI  - Home foreclosure, health, and mental health: a systematic review of individual,
      aggregate, and contextual associations.
AB  - BACKGROUND: The U.S. foreclosure crisis intensified markedly during the Great
      Recession of 2007-09, and currently an estimated five percent of U.S. residential
      properties are more than 90 days past due or in the process of foreclosure. Yet
      there has been no systematic assessment of the effects of foreclosure on health
      and mental health. METHODS AND FINDINGS: I applied systematic search terms to
      PubMed and PsycINFO to identify quantitative or qualitative studies about the
      relationship between home foreclosure and health or mental health. After
      screening the titles and abstracts of 930 publications and reviewing the full
      text of 76 articles, dissertations, and other reports, I identified 42
      publications representing 35 unique studies about foreclosure, health, and mental
      health. The majority of studies (32 [91%]) concluded that foreclosure had adverse
      effects on health or mental health, while three studies yielded null or mixed
      findings. Only two studies examined the extent to which foreclosure may have
      disproportionate impacts on ethnic or racial minority populations. CONCLUSIONS:
      Home foreclosure adversely affects health and mental health through channels
      operating at multiple levels: at the individual level, the stress of personally
      experiencing foreclosure was associated with worsened mental health and adverse
      health behaviors, which were in turn linked to poorer health status; at the
      community level, increasing degradation of the neighborhood environment had
      indirect, cross-level adverse effects on health and mental health. Early
      intervention may be able to prevent acute economic shocks from eventually
      developing into the chronic stress of foreclosure, with all of the attendant
      benefits this implies for health and mental health status. Programs designed to
      encourage early return of foreclosed properties back into productive use may have
      similar health and mental health benefits.

PMID- 25849963
TI  - Long-term outcomes of percutaneous cryoablation for patients with hepatocellular
      carcinoma within Milan criteria.
AB  - BACKGROUND: Accumulating evidences have suggested that percutaneous cryoablation
      could be a valuable alternative ablation therapy for HCC but there has been no
      large cohort-based analysis on its long-term outcomes. METHODS: A series of 866
      patients with Child-Pugh class A-B cirrhosis and HCC within Milan criteria who
      underwent percutaneous cryoablation was long-term followed. The safety, efficacy,
      5-year survival, and prognostic factors of percutaneous cryoablation in the
      treatment of HCC were analyzed. RESULTS: A total of 1197 HCC lesions were ablated
      with 1401 cryoablation sessions. Complete response (CR) was achieved in 1163
      (97.2%) lesions and 832 (96.1%) patients with 34 (2.8%) major complications, but
      no treatment-related mortality. After a median of 30.9 months follow-up, 502
      (60.3%) patients who achieved CR developed different types of recurrence. The
      cumulative local tumor recurrence rate was 24.2% at 5-years. Multiple tumor
      lesions, tumor size > 3 cm, and repeated ablation of same lesion were independent
      risk factors associated with local recurrence. The 5-year overall survival (OS)
      rates were 59.5%. Age < 36 years, HCC family history, baseline hepatitis B virus
      DNA >106 copies/ml, and three HCC lesions were independently and significantly
      negative predictors to the post-cryoablation OS. CONCLUSIONS: Percutaneous
      cryoablation is an effective therapy for patients with HCC within Milan criteria,
      with comparable efficacy, safety and long-term survival to the reported outcomes
      of radiofrequency ablation.

PMID- 25849964
TI  - Evaluation and validation of housekeeping genes as reference for gene expression
      studies in pigeonpea (Cajanus cajan) under drought stress conditions.
AB  - Gene expression analysis using quantitative real-time PCR (qRT-PCR) is a very
      sensitive technique and its sensitivity depends on the stable performance of
      reference gene(s) used in the study. A number of housekeeping genes have been
      used in various expression studies in many crops however, their expression were
      found to be inconsistent under different stress conditions. As a result, species
      specific housekeeping genes have been recommended for different expression
      studies in several crop species. However, such specific housekeeping genes have
      not been reported in the case of pigeonpea (Cajanus cajan) despite the fact that
      genome sequence has become available for the crop. To identify the stable
      housekeeping genes in pigeonpea for expression analysis under drought stress
      conditions, the relative expression variations of 10 commonly used housekeeping
      genes (EF1alpha, UBQ10, GAPDH, 18SrRNA, 25SrRNA, TUB6, ACT1, IF4alpha, UBC and
      HSP90) were studied on root, stem and leaves tissues of Asha (ICPL 87119). Three
      statistical algorithms geNorm, NormFinder and BestKeeper were used to define the
      stability of candidate genes. geNorm analysis identified IF4alpha and TUB6 as the
      most stable housekeeping genes however, NormFinder analysis determined IF4alpha
      and HSP90 as the most stable housekeeping genes under drought stress conditions.
      Subsequently validation of the identified candidate genes was undertaken in qRT
      PCR based gene expression analysis of uspA gene which plays an important role for
      drought stress conditions in pigeonpea. The relative quantification of the uspA
      gene varied according to the internal controls (stable and least stable genes),
      thus highlighting the importance of the choice of as well as validation of
      internal controls in such experiments. The identified stable and validated
      housekeeping genes will facilitate gene expression studies in pigeonpea
      especially under drought stress conditions. 

PMID- 25849965
TI  - Characterization of pediatric hospital-associated infection caused by methicillin
      resistant Staphylococcus aureus in mainland China.
AB  - BACKGROUND: This study was conducted to investigate the clinical features of
      hospital-associated infections (HAIs) caused by methicillin-resistant
      Staphylococcus aureus (MRSA) in Chinese children, and the molecular
      characteristics of the bacteria. METHODS: Patients with HAIs caused by MRSA were
      identified retrospectively. All isolates were analyzed using molecular typing and
      antimicrobial susceptibility tests. RESULTS: In total, 150 patients were
      identified, with a median age of 18 months. The most common infection was
      pneumonia (55.3%), followed by skin and soft tissue infections (46%). Invasive
      infections were observed in 52 patients (34.7%), and their hospital stay was
      longer compared with non-invasive cases (21 vs 12 days, p = 0.047). A total of 16
      sequence types (STs) were identified. ST239 and ST59 were common clones,
      accounting for 46% and 28% of cases, respectively. Compared with cases caused by
      ST239-SCCmecI-III, patients infected by ST59-SCCmecIV-V had a lower median age
      (11 vs 41 months, p = 0.047) and more commonly developed invasive infection (50%
      vs 18.8%, p = 0.006). CONCLUSIONS: Invasive infections accounted for a large
      proportion of HAIs caused by MRSA. ST59-SCCmecIV/V, a common clone in the
      community, caused HAIs in Chinese children, more often infected younger children
      and caused invasive infections.

PMID- 25849967
TI  - Photochromic phenoxyl-imidazolyl radical complexes with decoloration rates from
      tens of nanoseconds to seconds.
AB  - We report a novel photochromic molecular system, phenoxyl-imidazolyl radical
      complex (PIC), in which both a phenoxyl radical site and an imidazolyl radical
      site are reversibly and simultaneously generated upon UV light irradiation. PIC
      consists of the three parts: an aromatic linker, a diarylimidazole moiety, and a
      4H-cyclohexadienone ring. Upon UV light irradiation, the C-N bond between the 4H
      cyclohexadienone ring and the imidazole ring in the colorless closed-ring isomer
      of PIC undergoes a homolytic cleavage, leading to the formation of the transient
      colored open-ring isomer. Based on the substituents on the imidazoyl/4H
      cyclohexadienone rings and the nature of the aromatic linker, the half-life of
      the colored open-ring isomer can be varied between tens of nanoseconds and
      seconds. PIC derivatives containing a 1,2-phenylene linker exhibit high fatigue
      resistance toward repeated photochromic reactions. Analysis using laser flash
      photolysis reveals that the absorption spectra of the open-ring isomers are not
      readily rationalized by a straightforward superposition of the spectra of the two
      component radical fragments and the photogenerated radicals are electronically
      coupled through the aromatic linker. Furthermore, the open-ring isomer can be
      treated as a hybrid of the pure open-shell biradical and closed-shell quinoid
      resonance structures. 

PMID- 25849966
TI  - Mechanisms of endocrine resistance in breast cancer: an overview of the proposed
      roles of noncoding RNA.
AB  - Endocrine therapies such as tamoxifen and aromatase inhibitors are the standard
      treatment options for estrogen receptor-positive breast cancer patients. However,
      resistance to these agents has become a major clinical obstacle. Potential
      mechanisms of resistance to endocrine therapies have been identified, often
      involving enhanced growth factor signaling and changes in the expression or
      action of the estrogen receptor, but few studies have addressed the role of
      noncoding RNA (ncRNA). Two important types of ncRNA include microRNA (miRNA) and
      long noncoding RNA (lncRNA). miRNAs are small RNA molecules that regulate gene
      expression via translational inhibition or degradation of mRNA transcripts, while
      lncRNAs are larger RNA molecules that have been shown to play a role in multiple
      cellular maintenance functions such as protein scaffolding, chromatin looping,
      and regulation of mRNA stability. Both miRNA and lncRNA have recently impacted
      the field of breast cancer research as important pieces in the mechanistic puzzle
      of the genes and pathways involved in breast cancer development and progression.
      This review serves as an overview of the roles of miRNA and lncRNA in breast
      cancer progression and the development of endocrine resistance. Ideally, future
      experiments in the field should include identification of ncRNAs that could be
      potential therapeutic targets in endocrine-resistant tumors, as well as ncRNA
      biomarkers that facilitate more tumor-specific treatment options for endocrine
      resistant breast cancer patients. 

PMID- 25849968
TI  - Examination of the Mild Brain Injury Atypical Symptom Scale and the Validity-10
      Scale to detect symptom exaggeration in US military service members.
AB  - OBJECTIVE: The purpose of this study was to examine the clinical utility of two
      validity scales designed for use with the Neurobehavioral Symptom Inventory (NSI)
      and the PTSD Checklist-Civilian Version (PCL-C); the Mild Brain Injury Atypical
      Symptoms Scale (mBIAS) and Validity-10 scale. METHOD: Participants were 63 U.S.
      military service members (age: M = 31.9 years, SD = 12.5; 90.5% male) who
      sustained a mild traumatic brain injury (MTBI) and were prospectively enrolled
      from Walter Reed National Military Medical Center. Participants were divided into
      two groups based on the validity scales of the Minnesota Multiphasic Personality
      Inventory-2 Restructured Form (MMPI-2-RF): (a) symptom validity test (SVT)-Fail
      (n = 24) and (b) SVT-Pass (n = 39). Participants were evaluated on average 19.4
      months postinjury (SD = 27.6). RESULTS: Participants in the SVT-Fail group had
      significantly higher scores (p < .05) on the mBIAS (d = 0.85), Validity-10 (d =
      1.89), NSI (d = 2.23), and PCL-C (d = 2.47), and the vast majority of the MMPI-2
      RF scales (d = 0.69 to d = 2.47). Sensitivity, specificity, and predictive power
      values were calculated across the range of mBIAS and Validity-10 scores to
      determine the optimal cutoff to detect symptom exaggeration. For the mBIAS, a
      cutoff score of >=8 was considered optimal, which resulted in low sensitivity
      (.17), high specificity (1.0), high positive predictive power (1.0), and moderate
      negative predictive power (.69). For the Validity-10 scale, a cutoff score of
      >=13 was considered optimal, which resulted in moderate-high sensitivity (.63),
      high specificity (.97), and high positive (.93) and negative predictive power
      (.83). CONCLUSION: These findings provide strong support for the use of the
      Validity-10 as a tool to screen for symptom exaggeration when administering the
      NSI and PCL-C. The mBIAS, however, was not a reliable tool for this purpose and
      failed to identify the vast majority of people who exaggerated symptoms.

PMID- 25849969
TI  - An automated clinical alert system for newly-diagnosed atrial fibrillation.
AB  - OBJECTIVE: Clinical decision support systems that notify providers of abnormal
      test results have produced mixed results. We sought to develop, implement, and
      evaluate the impact of a computer-based clinical alert system intended to improve
      atrial fibrillation stroke prophylaxis, and identify reasons providers do not
      implement a guideline-concordant response. MATERIALS AND METHODS: We conducted a
      cohort study with historical controls among patients at a tertiary care hospital.
      We developed a decision rule to identify newly-diagnosed atrial fibrillation,
      automatically notify providers, and direct them to online evidence-based
      management guidelines. We tracked all notifications from December 2009 to
      February 2010 (notification period) and applied the same decision rule to all
      patients from December 2008 to February 2009 (control period). Primary outcomes
      were accuracy of notification (confirmed through chart review) and prescription
      of warfarin within 30 days. RESULTS: During the notification period 604
      notifications were triggered, of which 268 (44%) were confirmed as newly
      diagnosed atrial fibrillation. The notifications not confirmed as newly-diagnosed
      involved patients with no recent electrocardiogram at our institution. Thirty
      four of 125 high-risk patients (27%) received warfarin in the notification
      period, compared with 34 of 94 (36%) in the control period (odds ratio, 0.66 [95%
      CI, 0.37-1.17]; p = 0.16). Common reasons to not prescribe warfarin (identified
      from chart review of 151 patients) included upcoming surgical procedure, choice
      to use aspirin, and discrepancy between clinical notes and the medication record.
      CONCLUSIONS: An automated system to identify newly-diagnosed atrial fibrillation,
      notify providers, and encourage access to management guidelines did not change
      provider behaviors.

PMID- 25849970
TI  - IL-21R signaling suppresses IL-17+ gamma delta T cell responses and production of
      IL-17 related cytokines in the lung at steady state and after Influenza A virus
      infection.
AB  - Influenza A virus (IAV) infection of the respiratory tract elicits a robust
      immune response, which is required for efficient virus clearance but at the same
      time can contribute to lung damage and enhanced morbidity. IL-21 is a member of
      the type I cytokine family and has many different immune-modulatory functions
      during acute and chronic virus infections, although its role in IAV infection has
      not been fully evaluated. In this report we evaluated the contributions of IL
      21/IL-21 receptor (IL-21R) signaling to host defense in a mouse model of primary
      IAV infection using IL-21R knock out (KO) mice. We found that lack of IL-21R
      signaling had no significant impact on virus clearance, adaptive T cell
      responses, or myeloid cell accumulations in the respiratory tract. However, a
      subset of inflammatory cytokines were elevated in the bronchoalveolar lavage
      fluid of IL-21R KO mice, including IL-17. Although there was only a small
      increase in Th17 cells in the lungs of IL-21R KO mice, we observed a dramatic
      increase in gamma delta (gammadelta) T cells capable of producing IL-17 both
      after IAV infection and at steady state in the respiratory tract. Finally, we
      found that IL-21R signaling suppressed the accumulation of IL-17+ gammadelta T
      cells in the respiratory tract intrinsically. Thus, our study reveals a
      previously unrecognized role of IL-21R signaling in regulating IL-17 production
      by gammadelta T cells. 

PMID- 25849971
TI  - Dietary galacto-oligosaccharides prevent airway eosinophilia and
      hyperresponsiveness in a murine house dust mite-induced asthma model.
AB  - BACKGROUND: Allergic asthma is strongly associated with the exposure to house
      dust mite (HDM) and is characterized by eosinophilic pulmonary inflammation and
      airway hyperresponsiveness (AHR). Recently, there is an increased interest in
      using dietary oligosaccharides, also known as prebiotics, as a novel strategy to
      prevent the development of, or reduce, symptoms of allergy. AIM: We investigated
      the preventive capacity of dietary galacto-oligosaccharides (GOS) compared to an
      intra-airway therapeutic treatment with budesonide on the development of HDM
      induced allergic asthma in mice. METHODS: BALB/c mice were intranasally
      sensitized with 1 MUg HDM on day 0 followed by daily intranasal challenge with
      PBS or 10 MUg HDM on days 7 to 11. Two weeks prior to the first sensitization and
      throughout the experiment mice were fed a control diet or a diet containing 1%
      GOS. Reference mice were oropharyngeally instilled with budesonide (500 MUg/kg)
      on days 7, 9, 11, and 13, while being fed the control diet. On day 14, AHR was
      measured by nebulizing increasing doses of methacholine into the airways. At the
      end of the experiment, bronchoalveolar lavage fluid (BALF) and lungs were
      collected. RESULTS: Sensitization and challenge with HDM resulted in AHR. In
      contrast to budesonide, dietary intervention with 1% GOS prevented the
      development of AHR. HDM sensitization and challenge resulted in a significant
      increase in BALF leukocytes numbers, which was suppressed by budesonide treatment
      and dietary intervention with 1% GOS. Moreover, HDM sensitization and challenge
      resulted in significantly enhanced concentrations of IL-6, CCL17, IL-33, CCL5 and
      IL-13 in lung tissue. Both dietary intervention with 1% GOS or budesonide
      treatment significantly decreased the HDM-induced increased concentrations of
      CCL5 and IL-13 in lung tissue, while budesonide also reduced the HDM-enhanced
      concentrations of IL-6 and CCL17 in lung tissue. CONCLUSION: Not only did dietary
      intervention with 1% GOS during sensitization and challenge prevent the induction
      of airway eosinophilia and Th2-related cytokine and chemokine concentrations in
      the lung equally effective as budesonide treatment, it also prevented AHR
      development in HDM-allergic mice. GOS might be useful for the prevention and/or
      treatment of symptoms in asthmatic disease.

PMID- 25849972
TI  - One-step immunoassay for tetrabromobisphenol a using a camelid single domain
      antibody-alkaline phosphatase fusion protein.
AB  - Tetrabromobisphenol A (TBBPA) is a ubiquitous brominated flame retardant, showing
      widespread environmental and human exposures. A variable domain of the heavy
      chain antibody (VHH), naturally occurring in camelids, approaches the lower size
      limit of functional antigen-binding entities. The ease of genetic manipulation
      makes such VHHs a superior choice to use as an immunoreagent. In this study, a
      highly selective anti-TBBPA VHH T3-15 fused with alkaline phosphatase (AP) from
      E. coli was expressed, showing both an integrated TBBPA-binding capacity and
      enzymatic activity. A one-step immunoassay based on the fusion protein T3-15-AP
      was developed for TBBPA in 5% dimethyl sulfoxide (DMSO)/phosphate buffered saline
      (PBS, pH 7.4), with a half-maximum signal inhibition concentration (IC50) of 0.20
      ng mL(-1). Compared to the parental VHH T3-15, T3-15-AP was able to bind to a
      wider variety of coating antigens and the assay sensitivity was slightly
      improved. Cross-reactivity of T3-15-AP with a set of important brominated
      analogues was negligible (<0.1%). Although T3-15-AP was susceptible to extreme
      heat (90  degrees C), much higher binding stability at ambient temperature was
      observed in the T3-15-AP-based assay for at least 70 days. A simple pretreatment
      method of diluting urine samples with DMSO was developed for a one-step assay.
      The recoveries of TBBPA from urine samples via this one-step assay ranged from
      96.7% to 109.9% and correlated well with a high-performance liquid chromatography
      tandem mass spectroscopy (HPLC-MS/MS) method. It is expected that the dimerized
      fusion protein, VHH-AP, will show promising applications in human exposure and
      environmental monitoring. 

PMID- 25849974
TI  - Editorial Comment for Silay et al.

PMID- 25849975
TI  - Selective contributions of neuronal and astroglial interleukin-1 receptor 1 to
      the regulation of sleep.
AB  - Interactions between sleep and immune function are bidirectional. Although the
      mechanisms that govern these interactions are not fully elucidated, the pro
      inflammatory cytokine, interleukin-1beta (IL-1), is a known regulator of sleep
      and mediator of immune responses. To further clarify the underlying substrates of
      sleep and immune interactions, we engineered two transgenic mouse lines that
      express interleukin-1 receptor 1 (IL1R1) only in the central nervous system (CNS)
      and selectively on neurons (NSE-IL1R1) or astrocytes (GFAP-IL1R1). During
      spontaneous sleep, compared to wild type (WT) animals, NSE-IL1R1 and GFAP-IL1R1
      mice have more rapid eye movement sleep (REMS) that is characterized by reduced
      theta power in the electroencephalogram (EEG) spectra. The non-REM sleep (NREMS)
      EEG of each of the IL1R1 transgenic mouse strains also is characterized by
      enhanced power in the delta frequency band. In response to 6h of sleep
      deprivation, sleep of both IL1R1 transgenic mouse strains is more consolidated
      than that of WT animals. Additionally, the NREMS EEG of NSE-IL1R1 mice contains
      less delta power after sleep deprivation, suggesting astroglial IL1R1 activity
      may modulate sleep homeostasis. Intracerebroventricular injection of IL-1 fails
      to alter sleep or brain temperature of NSE-IL1R1 or GFAP-IL1R1 mice. These data
      suggest that selective IL1R1 expression on neurons or on astrocytes is not
      sufficient for centrally-administered IL-1 to induce sleep or fever. Lack of
      sleep and febrile responses to IL-1 in these IL1R1 transgenic mouse strains may
      be due to their inability to produce IL-6 in brain. Overall, these studies
      demonstrate, through the use of novel transgenic mice, that IL1R1 on neurons and
      astrocytes differentially mediates aspects of sleep under physiological
      conditions and in response to central IL-1 administration. 

PMID- 25849976
TI  - Sleep and immunity: A growing field with clinical impact.

PMID- 25849977
TI  - Latent semantics of action verbs reflect phonetic parameters of intensity and
      emotional content.
AB  - Conjuring up our thoughts, language reflects statistical patterns of word co
      occurrences which in turn come to describe how we perceive the world. Whether
      counting how frequently nouns and verbs combine in Google search queries, or
      extracting eigenvectors from term document matrices made up of Wikipedia lines
      and Shakespeare plots, the resulting latent semantics capture not only the
      associative links which form concepts, but also spatial dimensions embedded
      within the surface structure of language. As both the shape and movements of
      objects have been found to be associated with phonetic contrasts already in
      toddlers, this study explores whether articulatory and acoustic parameters may
      likewise differentiate the latent semantics of action verbs. Selecting 3 * 20
      emotion-, face-, and hand-related verbs known to activate premotor areas in the
      brain, their mutual cosine similarities were computed using latent semantic
      analysis LSA, and the resulting adjacency matrices were compared based on two
      different large scale text corpora: HAWIK and TASA. Applying hierarchical
      clustering to identify common structures across the two text corpora, the verbs
      largely divide into combined mouth and hand movements versus emotional
      expressions. Transforming the verbs into their constituent phonemes, and
      projecting them into an articulatory space framed by tongue height and formant
      frequencies, the clustered small and large size movements appear differentiated
      by front versus back vowels corresponding to increasing levels of arousal.
      Whereas the clustered emotional verbs seem characterized by sequences of close
      versus open jaw produced phonemes, generating up- or downwards shifts in formant
      frequencies that may influence their perceived valence. Suggesting, that the
      latent semantics of action verbs reflect parameters of intensity and emotional
      polarity that appear correlated with the articulatory contrasts and acoustic
      characteristics of phonemes. 

PMID- 25849978
TI  - Analysis of xyloglucan endotransglycosylase/hydrolase (XTH) genes and diverse
      roles of isoenzymes during persimmon fruit development and postharvest softening.
AB  - Xyloglucan endotransglycosylase/hydrolase (XTH) enzymes have played a role in the
      remodeling of cell wall hemicelluloses. To investigate the function of XTHs in
      persimmon (Diospyros kaki L.) fruit development and postharvest softening, five
      cDNAs (DkXTH1 to DkXTH5), whose putative proteins contained the conserved
      DEIDFEFLG motif of XTH, were cloned. Real time quantitative PCR analysis revealed
      that DkXTH1, DkXTH4, and DkXTH5 peaked in immature expanding fruit, and their
      higher expression was observed along with higher fruit firmness in cold-treated
      fruit or firmer cultivar fruit during storage. The opposite gene expression
      patterns were observed in DkXTH2 and DkXTH3, which reached maxima concomitance
      with pronounced fruit softening. Meanwhile, the xyloglucan endotransglycosylase
      (XET) enzymes play important roles in both the rapid growth and ripening of
      persimmon fruit. Furthermore, the recombined DkXTH1 and DkXTH2 proteins showed
      significant XET activity without any detected XEH activity. However, the XET
      activity of recombined DkXTH2 protein had a higher affinity for small acceptor
      molecules than that of recombined DkXTH1 protein. The former might prefer to
      participate in cell wall restructuring, and the latter is more inclined to
      participate in cell wall assembly. Besides, DKXTH proteins could function by
      targeting to the cell wall under regulation of a signal peptide. The data
      suggested that individual DKXTHs could exhibit different patterns of expression,
      and the encoded products possessed specific enzymatic properties conferring on
      their respective functions in growth and postharvest softening of persimmon
      fruit. 

PMID- 25849979
TI  - Preload-based starling-like control for rotary blood pumps: numerical comparison
      with pulsatility control and constant speed operation.
AB  - In this study, we evaluate a preload-based Starling-like controller for
      implantable rotary blood pumps (IRBPs) using left ventricular end-diastolic
      pressure (PLVED) as the feedback variable. Simulations are conducted using a
      validated mathematical model. The controller emulates the response of the natural
      left ventricle (LV) to changes in PLVED. We report the performance of the preload
      based Starling-like controller in comparison with our recently designed
      pulsatility controller and constant speed operation. In handling the transition
      from a baseline state to test states, which include vigorous exercise, blood loss
      and a major reduction in the LV contractility (LVC), the preload controller
      outperformed pulsatility control and constant speed operation in all three test
      scenarios. In exercise, preload-control achieved an increase of 54% in mean pump
      flow ([Formula: see text]) with minimum loading on the LV, while pulsatility
      control achieved only a 5% increase in flow and a decrease in mean pump speed. In
      a hemorrhage scenario, the preload control maintained the greatest safety margin
      against LV suction. PLVED for the preload controller was 4.9 mmHg, compared with
      0.4 mmHg for the pulsatility controller and 0.2 mmHg for the constant speed mode.
      This was associated with an adequate mean arterial pressure (MAP) of 84 mmHg. In
      transition to low LVC, [Formula: see text] for preload control remained constant
      at 5.22 L/min with a PLVED of 8.0 mmHg. With regards to pulsatility control,
      [Formula: see text] fell to the nonviable level of 2.4 L/min with an associated
      PLVED of 16 mmHg and a MAP of 55 mmHg. Consequently, pulsatility control was
      deemed inferior to constant speed mode with a PLVED of 11 mmHg and a [Formula:
      see text] of 5.13 L/min in low LVC scenario. We conclude that pulsatility control
      imposes a danger to the patient in the severely reduced LVC scenario, which can
      be overcome by using a preload-based Starling-like control approach. 

PMID- 25849980
TI  - LPA signaling initiates schizophrenia-like brain and behavioral changes in a
      mouse model of prenatal brain hemorrhage.
AB  - Genetic, environmental and neurodevelopmental factors are thought to underlie the
      onset of neuropsychiatric disorders such as schizophrenia. How these risk factors
      collectively contribute to pathology is unclear. Here, we present a mouse model
      of prenatal intracerebral hemorrhage--an identified risk factor for schizophrenia
      -using a serum-exposure paradigm. This model exhibits behavioral, neurochemical
      and schizophrenia-related gene expression alterations in adult females.
      Behavioral alterations in amphetamine-induced locomotion, prepulse inhibition,
      thigmotaxis and social interaction--in addition to increases in tyrosine
      hydroxylase-positive dopaminergic cells in the substantia nigra and ventral
      tegmental area and decreases in parvalbumin-positive cells in the prefrontal
      cortex--were induced upon prenatal serum exposure. Lysophosphatidic acid (LPA), a
      lipid component of serum, was identified as a key molecular initiator of
      schizophrenia-like sequelae induced by serum. Prenatal exposure to LPA alone
      phenocopied many of the schizophrenia-like alterations seen in the serum model,
      whereas pretreatment with an antagonist against the LPA receptor subtype LPA1
      prevented many of the behavioral and neurochemical alterations. In addition, both
      prenatal serum and LPA exposure altered the expression of many genes and pathways
      related to schizophrenia, including the expression of Grin2b, Slc17a7 and Grid1.
      These findings demonstrate that aberrant LPA receptor signaling associated with
      fetal brain hemorrhage may contribute to the development of some neuropsychiatric
      disorders.

PMID- 25849981
TI  - The role of glucocorticoid receptor-dependent activity in the amygdala central
      nucleus and reversibility of early-life stress programmed behavior.
AB  - Early-life stress (ELS) leads to sustained changes in gene expression and
      behavior, increasing the likelihood of developing a psychiatric disorder in
      adulthood. The neurobiological basis for the later-in-life psychopathology is
      relatively unknown. The current study used a mouse model of ELS, achieved by
      daily maternal separations during the first 2 weeks of postnatal life, to test
      the role of amygdalar glucocorticoid receptor (GR) function in mediating the
      persistent increase in risk-taking behaviors. ELS produced a decrease in GR mRNA
      in the brain, with a notable reduction in the amygdala that was associated with
      sustained alterations in anxiety, fear and sociability-like behaviors. Lentiviral
      mediated restoration of the GR mRNA deficit, specifically within the adult
      central nucleus of the amygdala (CeA), reversed the enduring changes in anxiety
      and social behavior after ELS. These results provide evidence of lasting changes
      in CeA GR neural circuitry following ELS and suggest a mechanistic role for GR
      regulated processes in the CeA in mediating the lifelong maladaptive behaviors of
      ELS. We demonstrate that the long-lasting behavioral effects of ELS are
      reversible later in life and implicate the involvement of CeA GR-dependent
      activity in the sustained dysregulation of emotion following ELS. 

PMID- 25849982
TI  - Allergic fetal priming leads to developmental, behavioral and neurobiological
      changes in mice.
AB  - The state of the mother's immune system during pregnancy has an important role in
      fetal development and disruptions in the balance of this system are associated
      with a range of neurologic, neuropsychiatric and neurodevelopmental disorders.
      Epidemiological and clinical reports reveal various clues that suggest a possible
      association between developmental neuropsychiatric disorders and family history
      of immune system dysfunction. Over the past three decades, analogous increases
      have been reported in both the incidence of neurodevelopmental disorders and
      immune-related disorders, particularly allergy and asthma, raising the question
      of whether allergic asthma and characteristics of various neurodevelopmental
      disorders share common causal links. We used a mouse model of maternal allergic
      asthma to test this novel hypothesis that early fetal priming with an allergenic
      exposure during gestation produces behavioral deficits in offspring. Mothers were
      primed with an exposure to ovalbumin (OVA) before pregnancy, then exposed to
      either aerosolized OVA or vehicle during gestation. Both male and female mice
      born to mothers exposed to aerosolized OVA during gestation exhibited altered
      developmental trajectories in weight and length, decreased sociability and
      increased marble-burying behavior. Moreover, offspring of OVA-exposed mothers
      were observed to have increased serotonin transporter protein levels in the
      cortex. These data demonstrate that behavioral and neurobiological effects can be
      elicited following early fetal priming with maternal allergic asthma and provide
      support that maternal allergic asthma may, in some cases, be a contributing
      factor to neurodevelopmental disorders.

PMID- 25849983
TI  - D-cycloserine to enhance extinction of cue-elicited craving for alcohol: a
      translational approach.
AB  - Cue-elicited craving for alcohol is well established but extinction-based
      treatment to extinguish this response has generated only modest positive outcomes
      in clinical trials. Basic and clinical research suggests that D-cycloserine (DCS)
      enhances extinction to fear cues under certain conditions. However, it remains
      unclear whether DCS would also accelerate extinction of cue-elicited craving for
      alcohol. The goal of the current study was to examine whether, compared with
      placebo (PBO), DCS enhanced extinction of cue-elicited craving among treatment
      seeking individuals with alcohol use disorders (AUDs). Participants were
      administered DCS (50 mg) or PBO 1 h before an alcohol extinction paradigm in a
      simulated bar environment on two occasions. The extinction procedures occurred 1
      week apart and were fully integrated into outpatient treatment. Subjective
      craving for alcohol was the primary variable of interest. Follow-up cue
      reactivity sessions were conducted 1 week and 3 weeks later to ascertain
      persisting DCS effects. Drinking outcomes and tolerability were also examined.
      DCS was associated with augmented reductions in alcohol craving to alcohol cues
      during the first extinction session and these effects persisted through all
      subsequent sessions, suggesting facilitation of extinction. Participants in the
      DCS condition reported significant short-term reductions in drinking, although
      these did not persist to follow-up, and found the medication highly tolerable.
      These findings provide evidence that DCS enhances extinction of cue-elicited
      craving for alcohol in individuals with AUDs in the context of outpatient
      treatment. The potential clinical utility of DCS is discussed, including
      methodological considerations and context-dependent learning.

PMID- 25849984
TI  - Maternal depression is associated with DNA methylation changes in cord blood T
      lymphocytes and adult hippocampi.
AB  - Depression affects 10-15% of pregnant women and has been associated with preterm
      delivery and later developmental, behavioural and learning disabilities. We
      tested the hypothesis that maternal depression is associated with DNA methylation
      alterations in maternal T lymphocytes, neonatal cord blood T lymphocytes and
      adult offspring hippocampi. Genome-wide DNA methylation of CD3+ T lymphocytes
      isolated from 38 antepartum maternal and 44 neonatal cord blood samples were
      analyzed using Illumina Methylation 450 K microarrays. Previously obtained
      methylation data sets using methylated DNA immunoprecipitation and array
      hybridization of 62 postmortem hippocampal samples of adult males were re
      analyzed to test associations with history of maternal depression. We found 145
      (false discovery rate (FDR) q<0.05) and 2520 (FDR q<0.1) differentially
      methylated CG-sites in cord blood T lymphocytes of neonates from the maternal
      depression group as compared with the control group. However, no significant DNA
      methylation differences were detected in the antepartum maternal T lymphocytes of
      our preliminary data set. We also detected 294 differentially methylated probes
      (FDR q<0.1) in hippocampal samples associated with history of maternal
      depression. We observed a significant overlap (P=0.002) of 33 genes with changes
      in DNA methylation in T lymphocytes of neonates and brains of adult offspring.
      Many of these genes are involved in immune system functions. Our results show
      that DNA methylation changes in offspring associated with maternal depression are
      detectable at birth in the immune system and persist to adulthood in the brain.
      This is consistent with the hypothesis that system-wide epigenetic changes are
      involved in life-long responses to maternal depression in the offspring. 

PMID- 25849985
TI  - Synaptic vesicle release regulates myelin sheath number of individual
      oligodendrocytes in vivo.
AB  - The myelination of axons by oligodendrocytes markedly affects CNS function, but
      how this is regulated by neuronal activity in vivo is not known. We found that
      blocking synaptic vesicle release impaired CNS myelination by reducing the number
      of myelin sheaths made by individual oligodendrocytes during their short period
      of formation. We also found that stimulating neuronal activity increased myelin
      sheath formation by individual oligodendrocytes. These data indicate that
      neuronal activity regulates the myelinating capacity of single oligodendrocytes. 

PMID- 25849986
TI  - Regulation of chromatin accessibility and Zic binding at enhancers in the
      developing cerebellum.
AB  - To identify chromatin mechanisms of neuronal differentiation, we characterized
      chromatin accessibility and gene expression in cerebellar granule neurons (CGNs)
      of the developing mouse. We used DNase-seq to map accessibility of cis-regulatory
      elements and RNA-seq to profile transcript abundance across postnatal stages of
      neuronal differentiation in vivo and in culture. We observed thousands of
      chromatin accessibility changes as CGNs differentiated, and verified, using
      H3K27ac ChIP-seq, reporter gene assays and CRISPR-mediated activation, that many
      of these regions function as neuronal enhancers. Motif discovery in
      differentially accessible chromatin regions suggested a previously unknown role
      for the Zic family of transcription factors in CGN maturation. We confirmed the
      association of Zic with these elements by ChIP-seq and found, using knockdown,
      that Zic1 and Zic2 are required for coordinating mature neuronal gene expression
      patterns. Together, our data reveal chromatin dynamics at thousands of gene
      regulatory elements that facilitate the gene expression patterns necessary for
      neuronal differentiation and function. 

PMID- 25849987
TI  - Neuronal activity biases axon selection for myelination in vivo.
AB  - An essential feature of vertebrate neural development is ensheathment of axons
      with myelin, an insulating membrane formed by oligodendrocytes. Not all axons are
      myelinated, but mechanisms directing myelination of specific axons are unknown.
      Using zebrafish, we found that activity-dependent secretion stabilized myelin
      sheath formation on select axons. When VAMP2-dependent exocytosis was silenced in
      single axons, oligodendrocytes preferentially ensheathed neighboring axons.
      Nascent sheaths formed on silenced axons were shorter in length, but when
      activity of neighboring axons was also suppressed, inhibition of sheath growth
      was relieved. Using in vivo time-lapse microscopy, we found that only 25% of
      oligodendrocyte processes that initiated axon wrapping were stabilized during
      normal development and that initiation did not require activity. Instead,
      oligodendrocyte processes wrapping silenced axons retracted more frequently. We
      propose that axon selection for myelination results from excessive and
      indiscriminate initiation of wrapping followed by refinement that is biased by
      activity-dependent secretion from axons. 

PMID- 25849988
TI  - Medial prefrontal cortical activity reflects dynamic re-evaluation during
      voluntary persistence.
AB  - Deciding how long to keep waiting for future rewards is a nontrivial problem,
      especially when the timing of rewards is uncertain. We carried out an experiment
      in which human decision makers waited for rewards in two environments in which
      reward-timing statistics favored either a greater or lesser degree of behavioral
      persistence. We found that decision makers adaptively calibrated their level of
      persistence for each environment. Functional neuroimaging revealed signals that
      evolved differently during physically identical delays in the two environments,
      consistent with a dynamic and context-sensitive reappraisal of subjective value.
      This effect was observed in a region of ventromedial prefrontal cortex that is
      sensitive to subjective value in other contexts, demonstrating continuity between
      valuation mechanisms involved in discrete choice and in temporally extended
      decisions analogous to foraging. Our findings support a model in which voluntary
      persistence emerges from dynamic cost/benefit evaluation rather than from a
      control process that overrides valuation mechanisms. 

PMID- 25849989
TI  - Learning-induced autonomy of sensorimotor systems.
AB  - Distributed networks of brain areas interact with one another in a time-varying
      fashion to enable complex cognitive and sensorimotor functions. Here we used new
      network-analysis algorithms to test the recruitment and integration of large
      scale functional neural circuitry during learning. Using functional magnetic
      resonance imaging data acquired from healthy human participants, we investigated
      changes in the architecture of functional connectivity patterns that promote
      learning from initial training through mastery of a simple motor skill. Our
      results show that learning induces an autonomy of sensorimotor systems and that
      the release of cognitive control hubs in frontal and cingulate cortices predicts
      individual differences in the rate of learning on other days of practice. Our
      general statistical approach is applicable across other cognitive domains and
      provides a key to understanding time-resolved interactions between distributed
      neural circuits that enable task performance. 

PMID- 25849991
TI  - Composition, variation, expression and evolution of low-molecular-weight glutenin
      subunit genes in Triticum urartu.
AB  - BACKGROUND: Wheat (AABBDD, 2n = 6x = 42) is a major dietary component for many
      populations across the world. Bread-making quality of wheat is mainly determined
      by glutenin subunits, but it remains challenging to elucidate the composition and
      variation of low-molecular-weight glutenin subunits (LMW-GS) genes, the major
      components for glutenin subunits in hexaploid wheat. This problem, however, can
      be greatly simplified by characterizing the LMW-GS genes in Triticum urartu, the
      A-genome donor of hexaploid wheat. In the present study, we exploited the high
      throughput molecular marker system, gene cloning, proteomic methods and molecular
      evolutionary genetic analysis to reveal the composition, variation, expression
      and evolution of LMW-GS genes in a T. urartu population from the Fertile Crescent
      region. RESULTS: Eight LMW-GS genes, including four m-type, one s-type and three
      i-type, were characterized in the T. urartu population. Six or seven genes, the
      highest number at the Glu-A3 locus, were detected in each accession. Three i-type
      genes, each containing more than six allelic variants, were tightly linked
      because of their co-segregation in every accession. Only 2-3 allelic variants
      were detected for each m- and s-type gene. The m-type gene, TuA3-385, for which
      homologs were previously characterized only at Glu-D3 locus in common wheat and
      Aegilops tauschii, was detected at Glu-A3 locus in T. urartu. TuA3-460 was the
      first s-type gene identified at Glu-A3 locus. Proteomic analysis showed 1-4
      genes, mainly i-type, expressed in individual accessions. About 62% accessions
      had three active i-type genes, rather than one or two in common wheat.
      Southeastern Turkey might be the center of origin and diversity for T. urartu due
      to its abundance of LMW-GS genes/genotypes. Phylogenetic reconstruction
      demonstrated that the characterized T. urartu might be the direct donor of the
      Glu-A3 locus in common wheat varieties. CONCLUSIONS: Compared with the Glu-A3
      locus in common wheat, a large number of highly diverse LMW-GS genes and active
      genes were characterized in T. urartu, demonstrating that this progenitor might
      provide valuable genetic resources for LMW-GS genes to improve the quality of
      common wheat. The phylogenetic analysis provided molecular evidence and confirmed
      that T. urartu was the A-genome donor of hexaploid wheat.

PMID- 25849992
TI  - Men's facial width-to-height ratio predicts aggression: a meta-analysis.
AB  - Recent research has identified men's facial width-to-height ratio (fWHR) as a
      reliable predictor of aggressive tendencies and behavior. Other research,
      however, has failed to replicate the fWHR-aggression relationship and has
      questioned whether previous findings are robust. In the current paper, we
      synthesize existing work by conducting a meta-analysis to estimate whether and
      how fWHR predicts aggression. Our results indicate a small, but significant,
      positive relationship between men's fWHR and aggression. 

PMID- 25849990
TI  - Genetic variation at MECOM, TERT, JAK2 and HBS1L-MYB predisposes to
      myeloproliferative neoplasms.
AB  - Clonal proliferation in myeloproliferative neoplasms (MPN) is driven by somatic
      mutations in JAK2, CALR or MPL, but the contribution of inherited factors is
      poorly characterized. Using a three-stage genome-wide association study of 3,437
      MPN cases and 10,083 controls, we identify two SNPs with genome-wide significance
      in JAK2(V617F)-negative MPN: rs12339666 (JAK2; meta-analysis P=1.27 * 10(-10))
      and rs2201862 (MECOM; meta-analysis P=1.96 * 10(-9)). Two additional SNPs,
      rs2736100 (TERT) and rs9376092 (HBS1L/MYB), achieve genome-wide significance when
      including JAK2(V617F)-positive cases. rs9376092 has a stronger effect in
      JAK2(V617F)-negative cases with CALR and/or MPL mutations (Breslow-Day P=4.5 *
      10(-7)), whereas in JAK2(V617F)-positive cases rs9376092 associates with
      essential thrombocythemia (ET) rather than polycythemia vera (allelic chi(2)
      P=7.3 * 10(-7)). Reduced MYB expression, previously linked to development of an
      ET-like disease in model systems, associates with rs9376092 in normal myeloid
      cells. These findings demonstrate that multiple germline variants predispose to
      MPN and link constitutional differences in MYB expression to disease phenotype. 

PMID- 25849994
TI  - Effects of composition and processing variables on the oxidative stability of
      protein-based and oil-in-water food emulsions.
AB  - Because many common foods are emulsions (mayonnaise, coffee creamers, salad
      dressing, etc.), a better understanding of lipid oxidation mechanisms in these
      systems is crucial for the formulation, production, and storage of the relevant
      consumer products. A research body has focused on the microstructural and
      oxidative stability of protein-stabilized oil-in-water emulsions that are
      structurally similar to innovative products that have been recently developed by
      the food industry (e.g., non-dairy creams, vegetable fat spreads, etc.) This
      review presents recent findings about the factors that determine the development
      of lipid oxidation in emulsions where proteins constitute the stabilizing
      interface. Emphasis is given to "endogenous" factors, such as those of
      compositional (e.g., protein/lipid phases, pH, presence of transition metals) or
      processing (e.g., temperature, droplet size) nature. Improved knowledge of the
      conditions that favor the oxidative protection of protein in emulsions can lead
      to their optimized use as food ingredients and thereby improve the organoleptic
      and nutritional value of the related products.

PMID- 25849993
TI  - Autophagy protects monocytes from Wolbachia heat shock protein 60-induced
      apoptosis and senescence.
AB  - Monocyte dysfunction by filarial antigens has been a major mechanism underlying
      immune evasion following hyporesponsiveness during patent lymphatic filariasis.
      Recent studies have initiated a paradigm shift to comprehend the immunological
      interactions of Wolbachia and its antigens in inflammation, apoptosis, lymphocyte
      anergy, etc. Here we showed that recombinant Wolbachia heat shock protein 60
      (rWmhsp60) interacts with TLR-4 and induces apoptosis in monocytes of endemic
      normal but not in chronic patients. Higher levels of reactive oxygen species
      (ROS) induced after TLR-4 stimulation resulted in loss of mitochondrial membrane
      potential and caspase cascade activation, which are the plausible reason for
      apoptosis. Furthermore, release in ROS owing to TLR-4 signaling resulted in the
      activation of NF-kappaB p65 nuclear translocation which leads to inflammation and
      apoptosis via TNF receptor pathway following the increase in IL-6 and TNF-alpha
      level. Here for the first time, we report that in addition to apoptosis, rWmhsp60
      antigen in filarial pathogenesis also induces molecular senescence in monocytes.
      Targeting TLR-4, therefore, presents a promising candidate for treating rWmhsp60
      induced apoptosis and senescence. Strikingly, induction of autophagy by rapamycin
      detains TLR-4 in late endosomes and subverts TLR-4-rWmhsp60 interaction, thus
      protecting TLR-4-mediated apoptosis and senescence. Furthermore, rapamycin
      induced monocytes were unresponsive to rWmhsp60, and activated lymphocytes
      following PHA stimulation. This study demonstrates that autophagy mediates the
      degradation of TLR-4 signaling and protects monocytes from rWmhsp60 induced
      apoptosis and senescence. 

PMID- 25849995
TI  - Psychometric properties of the Persian version of Death Depression Scale among
      nurses.
AB  - This study is an attempt to investigate validity and reliability of the Persian
      version of Death Depression Scale among male and female nurses at Jundishapur
      University of Medical Science and 2 private hospitals in Ahvaz, Iran, who were
      selected by a convenience sampling method after obtaining informed consent. They
      completed the Death Depression Scale-Revised (DDS-R), Death Anxiety Scale, Death
      Obsession Scale, as well as Short-Form of Beck Depression Questionnaire (BDI-13).
      The results of exploratory factor analysis on DDS-R identified 3 factors.
      Cronbach's alpha coefficient was 0.93 for the entire measure (19 items), with
      alphas ranging from .80 to .94 for the individual factors. Indices of concurrent
      validity for this scale with Death Anxiety, Death Obsession Scales, and BDI-13
      were all significant (p < 0.001). Given the validity and reliability of the DDS
      R, this scale can be used in clinical settings and research studies.

PMID- 25849996
TI  - Dynamic interplay of spectrosome and centrosome organelles in asymmetric stem
      cell divisions.
AB  - Stem cells have remarkable self-renewal ability and differentiation potency,
      which are critical for tissue repair and tissue homeostasis. Recently it has been
      found, in many systems (e.g. gut, neurons, and hematopoietic stem cells), that
      the self-renewal and differentiation balance is maintained when the stem cells
      divide asymmetrically. Drosophila male germline stem cells (GSCs), one of the
      best characterized model systems with well-defined stem cell niches, were
      reported to divide asymmetrically, where centrosome plays an important role.
      Utilizing time-lapse live cell imaging, customized tracking, and image processing
      programs, we found that most acentrosomal GSCs have the spectrosomes reposition
      from the basal end (wild type) to the apical end close to hub-GSC interface
      (acentrosomal GSCs). In addition, these apically positioned spectrosomes were
      mostly stationary while the basally positioned spectrosomes were mobile. For
      acentrosomal GSCs, their mitotic spindles were still highly oriented and divided
      asymmetrically with longer mitosis duration, resulting in asymmetric divisions.
      Moreover, when the spectrosome was knocked out, the centrosomes velocity
      decreased and centrosomes located closer to hub-GSC interface. We propose that in
      male GSCs, the spectrosome recruited to the apical end plays a complimentary role
      in ensuring proper spindle orientation when centrosome function is compromised. 

PMID- 25849997
TI  - Preparation of acetylsalicylic acid-acylated chitosan as a novel polymeric drug
      for drug controlled release.
AB  - The acetylsalicylic acid-acylated chitosan (ASACTS) with high degree of
      substitution (DS) was successfully synthesized, and characterized with FTIR, (1)H
      NMR and elemental analysis methods. The optimum synthesis conditions were
      obtained which gave the highest DS (about 60%) for ASACTS. Its drug release
      experiments were carried out in simulated gastric and intestine fluids. The
      results show that the drugs in the form of acetylsalicylic acid (ASA) and
      salicylic acid (SA) were released in a controlled manner from ASACTS only in
      simulated gastric fluid. The release profile can be best fitted with logistic and
      Weibull model. The research results reveal that ASACTS can be a potential
      polymeric drug for the controlled release of ASA and SA in the targeted gastric
      environment. 

PMID- 25849998
TI  - Interaction of a green ester-bonded gemini surfactant with xanthine oxidase:
      Biophysical perspective.
AB  - A multi technique approach was utilized to explore the interaction between a
      novel green gemini surfactant, ethane-1,2-diyl bis(N,N-dimethyl-N
      tetradecylammoniumacetoxy) dichloride (14-E2-14), with bovine milk xanthine
      oxidase (XO). Tensiometric, spectroscopic, microscopic and molecular modeling
      results demonstrate significant interaction and structural change of native
      xanthine oxidase upon 14-E2-14 combination. The results obtained in this study
      may be beneficial for scientists to calibrate conformation of the enzyme by novel
      biodegradable/green microstructures; consequently, it would likely add new
      impetus in understanding the treatment modes of various diseases like gout,
      hyperuricemia, liver and brain necrosis. Moreover, the 14-E2-14-XO interaction
      assists to unfurl new routes in the designing/selection of green-surfactant
      protein mixtures widely used in food processing, cosmetics, and pharmaceutical
      industries. 

PMID- 25849999
TI  - Fabrication of 3D porous silk scaffolds by particulate (salt/sucrose) leaching
      for bone tissue reconstruction.
AB  - Silk fibroin is a biomaterial being actively studied in the field of bone tissue
      engineering. In this study, we aimed to select the best strategy for bone
      reconstruction on scaffolds by changing various conditions. We compared the
      characteristics of each scaffold via structural analysis using scanning electron
      microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), the swelling
      ratio, water uptake, porosity, compressive strength, cell infiltration and cell
      viability (CCK-8). The scaffolds had high porosity with good inter pore
      connectivity and showed high compressive strength and modulus. In addition, to
      confirm bone reconstruction, animal studies were conducted in which samples were
      implanted in rat calvaria and investigated by micro-CT scans. In conclusion, the
      presented study indicates that using sucrose produces scaffolds showing better
      pore interconnectivity and cell infiltration than scaffolds made by using a salt
      process. In addition, in vivo experiments showed that hydroxyapatite accelerates
      bone reconstruction on implanted scaffolds. Accordingly, our scaffold will be
      expected to have a useful application in bone reconstruction. 

PMID- 25850000
TI  - Development and mechanism investigation of a new piperlongumine derivative as a
      potent anti-inflammatory agent.
AB  - Inflammation, especially chronic inflammation, is directly involvement in the
      pathogenesis of many diseases including cancer. An effective approach for
      managing inflammation is to employ chemicals to block activation of nuclear
      factor-kappaB (NF-kappaB), a key regulator for inflammatory processes.
      Piperlongumine (piplartine, PL), an electrophilic molecule isolated from Piper
      longum L., possesses excellent anti-cancer and anti-inflammatory properties. In
      this study, a new PL analogue (PL-0N) was designed by replacing nitrogen atom of
      lactam in PL with carbon atom to increase its electrophilicity and thus anti
      inflammatory activity. It was found that PL-0N is more potent than the parent
      compound in suppressing lipopolysaccharide (LPS)-induced secretion of nitric
      oxide and prostaglandin E2 as well as expression of inducible nitric oxide
      synthase and cyclooxygenase-2 in RAW264.7 macrophages. Mechanistic investigation
      implies that PL-0N exerts anti-inflammatory activity through inhibition of LPS
      induced NF-kappaB transduction pathway, down-regulation of LPS-induced MAPKs
      activation and impairment of proteasomal activity, but also enhancement of LPS
      induced autophagy; the inhibition of NF-kappaB by PL-0N is achieved at various
      stages by: (i) preventing phosphorylation of IKKalpha/beta, (ii) stabilizing the
      suppressor protein IkappaBalpha, (iii) interfering with the nuclear translocation
      of NF-kappaB, and (iv) inhibiting the DNA-binding of NF-kappaB. These data
      indicate that nitrogen-atom-lacking pattern is a successful strategy to improve
      anti-inflammatory property of PL, and that the novel molecule, PL-0N may be
      served as a promising lead for developing natural product-directed anti
      inflammatory agents. 

PMID- 25850001
TI  - Continuing treatment with Salvia miltiorrhiza injection attenuates myocardial
      fibrosis in chronic iron-overloaded mice.
AB  - Iron overload cardiomyopathy results from iron accumulation in the myocardium
      that is closely linked to iron-mediated myocardial fibrosis. Salvia miltiorrhiza
      (SM, also known as Danshen), a traditional Chinese medicinal herb, has been
      widely used for hundreds of years to treat cardiovascular diseases. Here, we
      investigated the effect and potential mechanism of SM on myocardial fibrosis
      induced by chronic iron overload (CIO) in mice. Kunming male mice (8 weeks old)
      were randomized to six groups of 10 animals each: control (CONT), CIO, low-dose
      SM (L-SM), high-dose SM (H-SM), verapamil (VRP) and deferoxamine (DFO) groups.
      Normal saline was injected in the CONT group. Mice in the other five groups were
      treated with iron dextran at 50 mg/kg per day intraperitoneally for 7 weeks, and
      those in the latter four groups also received corresponding daily treatments,
      including 3 g/kg or 6 g/kg of SM, 100 mg/kg of VRP, or 100 mg/kg of DFO. The iron
      deposition was estimated histologically using Prussian blue staining. Myocardial
      fibrosis was determined by Masson's trichrome staining and hydroxyproline (Hyp)
      quantitative assay. Superoxide dismutase (SOD) activity, malondialdehyde (MDA)
      content and protein expression levels of type I collagen (COL I), type I collagen
      (COL III), transforming growth factor-beta1 (TGF-beta1) and matrix
      metalloproteinase-9 (MMP-9) were analyzed to investigate the mechanisms
      underlying the effects of SM against iron-overloaded fibrosis. Treatment of
      chronic iron-overloaded mice with SM dose-dependently reduced iron deposition
      levels, fibrotic area percentage, Hyp content, expression levels of COL I and COL
      III, as well as upregulated the expression of TGF- beta1 and MMP-9 proteins in
      the heart. Moreover, SM treatment decreased MDA content and increased SOD
      activity. In conclusion, SM exerted activities against cardiac fibrosis induced
      by CIO, which may be attributed to its inhibition of iron deposition, as well as
      collagen metabolism and oxidative stress. 

PMID- 25850002
TI  - Mechanistic and Structural Analysis of a Drosophila melanogaster Enzyme,
      Arylalkylamine N-Acetyltransferase Like 7, an Enzyme That Catalyzes the Formation
      of N-Acetylarylalkylamides and N-Acetylhistamine.
AB  - Arylalkylamine N-acetyltransferase like 7 (AANATL7) catalyzes the formation of N
      acetylarylalkylamides and N-acetylhistamine from acetyl-CoA and the corresponding
      amine substrate. AANATL7 is a member of the GNAT superfamily of >10000 GCN5
      related N-acetyltransferases, many members being linked to important roles in
      both human metabolism and disease. Drosophila melanogaster utilizes the N
      acetylation of biogenic amines for the inactivation of neurotransmitters, the
      biosynthesis of melatonin, and the sclerotization of the cuticle. We have
      expressed and purified D. melanogaster AANATL7 in Escherichia coli and used the
      purified enzyme to define the substrate specificity for acyl-CoA and amine
      substrates. Information about the substrate specificity provides insight into the
      potential contribution made by AANATL7 to fatty acid amide biosynthesis because
      D. melanogaster has emerged as an important model system contributing to our
      understanding of fatty acid amide metabolism. Characterization of the kinetic
      mechanism of AANATL7 identified an ordered sequential mechanism, with acetyl-CoA
      binding first followed by histamine to generate an AANATL7.acetyl-CoA.histamine
      ternary complex prior to catalysis. Successive pH-activity profiling and site
      directed mutagenesis experiments identified two ionizable groups: one with a pKa
      of 7.1 that is assigned to Glu-26 as a general base and a second pKa of 9.5 that
      is assigned to the protonation of the thiolate of the coenzyme A product. Using
      the data generated herein, we propose a chemical mechanism for AANATL7 and define
      functions for other important amino acid residues involved in substrate binding
      and regulation of catalysis. 

PMID- 25850004
TI  - Advantages and limitations of the use of optogenetic approach in studying fast
      scale spike encoding.
AB  - Understanding single-neuron computations and encoding performed by spike
      generation mechanisms of cortical neurons is one of the central challenges for
      cell electrophysiology and computational neuroscience. An established paradigm to
      study spike encoding in controlled conditions in vitro uses intracellular
      injection of a mixture of signals with fluctuating currents that mimic in vivo
      like background activity. However this technique has two serious limitations: it
      uses current injection, while synaptic activation leads to changes of
      conductance, and current injection is technically most feasible in the soma,
      while the vast majority of synaptic inputs are located on the dendrites. Recent
      progress in optogenetics provides an opportunity to circumvent these limitations.
      Transgenic expression of light-activated ionic channels, such as
      Channelrhodopsin2 (ChR2), allows induction of controlled conductance changes even
      in thin distant dendrites. Here we show that photostimulation provides a useful
      extension of the tools to study neuronal encoding, but it has its own
      limitations. Optically induced fluctuating currents have a low cutoff (~70 Hz),
      thus limiting the dynamic range of frequency response of cortical neurons. This
      leads to severe underestimation of the ability of neurons to phase-lock their
      firing to high frequency components of the input. This limitation could be worked
      around by using short (2 ms) light stimuli which produce membrane potential
      responses resembling EPSPs by their fast onset and prolonged decay kinetics. We
      show that combining application of short light stimuli to different parts of
      dendritic tree for mimicking distant EPSCs with somatic injection of fluctuating
      current that mimics fluctuations of membrane potential in vivo, allowed us to
      study fast encoding of artificial EPSPs photoinduced at different distances from
      the soma. We conclude that dendritic photostimulation of ChR2 with short light
      pulses provides a powerful tool to investigate population encoding of simulated
      synaptic potentials generated in dendrites at different distances from the soma.

PMID- 25850005
TI  - Apparent pH sensitivity of solution-gated graphene transistors.
AB  - Solution-gated graphene transistors were developed recently for use in pH sensor
      applications. The device operation is understood to rely on the capability of
      hydronium and hydroxide ions in solution to change the electrical properties of
      graphene. However, hydronium and hydroxide ions are accompanied by other ionic
      species in a typical acidic or basic solution and, therefore, the roles of these
      other ionic species must be also considered to fully understand the pH response
      of such devices. Using series of pH buffer solutions designed carefully, we
      verified that the magnitude and even the direction of pH-dependent Dirac voltage
      (VDirac) shift (the typical pH sensing indicator) depend strongly on the
      concentration and composition of the buffers used. The results indicate that the
      interpretation of the apparent pH-dependent VDirac response of a solution-gated
      graphene transistor must include the contributions of the additional ions in the
      solution. 

PMID- 25850006
TI  - Serum fibroblast growth factor 21 levels is associated with lower extremity
      atherosclerotic disease in Chinese female diabetic patients.
AB  - BACKGROUND: Fibroblast growth factor 21 (FGF21) is an emerging metabolic
      regulator associated with glucose and lipid metabolism, and it is still unclear
      whether FGF21 is related to atherosclerosis. Here, we explored the potential link
      between FGF21 and lower extremity atherosclerotic disease (LEAD) in type 2
      diabetic patients. METHODS: A cross-sectional study was conducted on 504 type 2
      diabetic patients (283 men, 221 women). LEAD was defined by Ankle-brachial index
      (ABI) <0.9 and lower extremity arterial plaque evaluated by color Doppler
      ultrasound. Serum FGF21 concentrations were quantified by a sandwich enzyme
      linked immunosorbent assay. RESULTS: The total FGF21 levels of male and female
      patients had no significant differenence ((299.14(177.31-534.49) vs 362.50(214.01
      578.73), P=0.516). Serum FGF21 levels in LEAD group were significantly higher
      than non-LEAD group in females (385.34(243.89-661.54) vs 313.13(156.38-485.79),
      P=0.006), while not in male patients (295.52(177.09-549.64) vs 342.09 (198.70
      549.87), P=0.613). In diabetic women, subjects with LEAD had significantly higher
      serum FGF21 regardless of non-alcoholic fatty liver disease (NAFLD) (P < 0.05).
      And serum FGF21 levels were positively correlated with waist circumference and
      systolic blood pressure after adjusted for age and BMI (r=0.198, P=0.004;
      r=0.152, P=0.027; respectively). Moreover, FGF21 was independently tied to
      femoral intima-media thickness (FIMT) (beta=0.208, P=0.031). After adjusted for
      other LEAD risk factors, FGF21 was demonstrated to be an independent risk factor
      for LEAD in type 2 diabetic women (OR, 1.106; 95%CI 1.008-1.223; P=0.028). In
      addition, FGF21 was negatively correlated with estradiol in premenopausal
      diabetic women (r=-0.368, P=0.009). After adjusted for estradiol, serum FGF21
      levels were still positively associated with FIMT in premenopausal diabetic women
      (r=0.381, P=0.007). In diabetic men, serum FGF21 levels were correlated with
      triglyceride and C-reactive protein even after adjusted for age and BMI (r=0.204,
      P=0.001; r=0.312, P < 0.001; respectively). However, serum FGF21 was not an
      independent impact factor for LEAD in men (P > 0.05). CONCLUSIONS: Serum FGF21
      level independently and positively links LEAD in Chinese women with type 2
      diabetes. The gender difference may be due to different estrogen levels.

PMID- 25850007
TI  - Powerful regulatory systems and post-transcriptional gene silencing resist
      increases in cellulose content in cell walls of barley.
AB  - BACKGROUND: The ability to increase cellulose content and improve the stem
      strength of cereals could have beneficial applications in stem lodging and
      producing crops with higher cellulose content for biofuel feedstocks. Here, such
      potential is explored in the commercially important crop barley through the
      manipulation of cellulose synthase genes (CesA). RESULTS: Barley plants
      transformed with primary cell wall (PCW) and secondary cell wall (SCW) barley
      cellulose synthase (HvCesA) cDNAs driven by the CaMV 35S promoter, were analysed
      for growth and morphology, transcript levels, cellulose content, stem strength,
      tissue morphology and crystalline cellulose distribution. Transcript levels of
      the PCW HvCesA transgenes were much lower than expected and silencing of both the
      endogenous CesA genes and introduced transgenes was often observed. These plants
      showed no aberrant phenotypes. Although attempts to over-express the SCW HvCesA
      genes also resulted in silencing of the transgenes and endogenous SCW HvCesA
      genes, aberrant phenotypes were sometimes observed. These included brittle nodes
      and, with the 35S:HvCesA4 construct, a more severe dwarfing phenotype, where
      xylem cells were irregular in shape and partially collapsed. Reductions in
      cellulose content were also observed in the dwarf plants and transmission
      electron microscopy showed a significant decrease in cell wall thickness.
      However, there were no increases in overall crystalline cellulose content or stem
      strength in the CesA over-expression transgenic plants, despite the use of a
      powerful constitutive promoter. CONCLUSIONS: The results indicate that the
      cellulose biosynthetic pathway is tightly regulated, that individual CesA
      proteins may play different roles in the synthase complex, and that the
      sensitivity to CesA gene manipulation observed here suggests that in planta
      engineering of cellulose levels is likely to require more sophisticated
      strategies.

PMID- 25850009
TI  - Hepatitis: Tightening the grip on clearing HCV infection.

PMID- 25850008
TI  - Dysphagia: current reality and scope of the problem.
AB  - Dysphagia is a symptom of swallowing dysfunction that occurs between the mouth
      and the stomach. Although oropharyngeal dysphagia is a highly prevalent condition
      (occurring in up to 50% of elderly people and 50% of patients with neurological
      conditions) and is associated with aspiration, severe nutritional and respiratory
      complications and even death, most patients are not diagnosed and do not receive
      any treatment. By contrast, oesophageal dysphagia is less prevalent and less
      severe, but with better recognized symptoms caused by diseases affecting the
      enteric nervous system and/or oesophageal muscular layers. Recognition of the
      clinical relevance and complications of oesophageal and oropharyngeal dysphagia
      is growing among health-care professionals in many fields. In addition, the
      emergence of new methods to screen and assess swallow function at both the
      oropharynx and oesophagus, and marked advances in understanding the
      pathophysiology of these conditions, is paving the way for a new era of intensive
      research and active therapeutic strategies for affected patients. Indeed, a
      unified field of deglutology is developing, with new professional profiles to
      cover the needs of all patients with dysphagia in a nonfragmented way. 

PMID- 25850010
TI  - Thinprep plus Papanicolaou stain method is more sensitive than cytospin-coupled
      Wright Giems stain method in cerebrospinal fluid cytology for diagnosis of
      leptomeningeal metastasis from solid tumors.
AB  - BACKGROUND: The present study was designed to determine whether the Thinprep plus
      Papanicolaou stain (Thinprep) method is more sensitive than the Cytospin-coupled
      Wright-Giemsa (WG) stain (Cytospin) method in diagnosis of leptomeningeal
      metastasis (LM) from malignant solid tumors in cerebrospinal fluid (CSF). We also
      explored if the Thinprep method could be used in the differential diagnosis of
      the type of primary tumor cells based on the morphology of tumor cells in CSF
      samples. METHODS: The morphological features of tumor cells in fresh CSF samples
      were analyzed using both methods. The tumor cell detection rates were compared
      between the two methods. RESULTS: Using the Thinprep method, we found that each
      type of tumor cells in the CSF samples had specific identifiable morphological
      features linked to their primary cancer origins, such as adenocarcinomas
      originated from the lungs, breast, and stomach, and lung squamous cell
      carcinomas, small cell lung cancer, large-cell neuroendocrine lung cancer,
      hepatocellular carcinoma, and malignant melanoma. In a retrospective study with
      88 LM patients, cancer cells were detected in 80 out of the 88 CSF samples. In
      the comparative study with 45 LM patients, the initial detection rate of the
      Thinprep method was significantly higher than that of the Cytospin method (73.3%
      vs. 57.8%, P<0.01). The cell morphology was better preserved and subcellular
      structures were clearer using the Thinprep method, compared to the Cytospin
      method. CONCLUSIONS: The Thinprep method is more sensitive and suitable for LM
      diagnosis in CSF in patients with malignant solid tumors than the Cytospin
      method. The Thinprep method may facilitate primary tumor detection and help
      design early treatment regimens for LM patients with tumors of unknown primary
      origin.

PMID- 25850011
TI  - Dioxygen activation and two consecutive oxidative decarboxylations of
      phenylpyruvate by nonheme iron(II) complexes: functional models of
      hydroxymandelate synthase (HMS) and CloR.
AB  - Two mononuclear iron(ii)-phenylpyruvate complexes of monoanionic facial N3
      ligands are reported to react with dioxygen to undergo two consecutive oxidative
      decarboxylation steps via an iron-mandelate complex mimicking the function of HMS
      and CloR. 

PMID- 25850013
TI  - Edaravone enhances brain-derived neurotrophic factor production in the ischemic
      mouse brain.
AB  - Edaravone, a clinical drug used to treat strokes, protects against neuronal cell
      death and memory loss in the ischemic brains of animal models through its
      antioxidant activity. In the present study, we subcutaneously administrated
      edaravone to mice (3 mg/kg/day) for three days immediately after bilateral common
      carotid artery occlusion, and revealed through an immunohistochemical analysis
      that edaravone (1) accelerated increases in the production of brain-derived
      neurotrophic factor (BDNF) in the hippocampus; (2) increased the number of
      doublecortin-positive neuronal precursor cells in the dentate gyrus subgranular
      zone; and (3) suppressed the ischemia-induced inactivation of calcium-calmodulin
      dependent protein kinase II in the hippocampus. We also revealed through a
      Western blotting analysis that edaravone (4) induced the phosphorylation of cAMP
      response element-binding (CREB), a transcription factor that regulates BDNF gene
      expression; and (5) induced the phosphorylation of extracellular signal-regulated
      kinases 1/2, an upstream signal factor of CREB. These results suggest that the
      neuroprotective effects of edaravone following brain ischemia were mediated not
      only by the elimination of oxidative stress, but also by the induction of BDNF
      production. 

PMID- 25850012
TI  - Reactive oxygen species, apoptosis, antimicrobial peptides and human inflammatory
      diseases.
AB  - Excessive free radical generation, especially reactive oxygen species (ROS)
      leading to oxidative stress in the biological system, has been implicated in the
      pathogenesis and pathological conditions associated with diverse human
      inflammatory diseases (HIDs). Although inflammation which is considered
      advantageous is a defensive mechanism in response to xenobiotics and foreign
      pathogen; as a result of cellular damage arising from oxidative stress, if
      uncontrolled, it may degenerate to chronic inflammation when the ROS levels
      exceed the antioxidant capacity. Therefore, in the normal resolution of
      inflammatory reactions, apoptosis is acknowledged to play a crucial role, while
      on the other hand, dysregulation in the induction of apoptosis by enhanced ROS
      production could also result in excessive apoptosis identified in the
      pathogenesis of HIDs. Apparently, a careful balance must be maintained in this
      complex environment. Antimicrobial peptides (AMPs) have been proposed in this
      review as an excellent candidate capable of playing prominent roles in
      maintaining this balance. Consequently, in novel drug design for the treatment
      and management of HIDs, AMPs are promising candidates owing to their size and
      multidimensional properties as well as their wide spectrum of activities and
      indications of reduced rate of resistance. 

PMID- 25850014
TI  - Enhancement of antiproliferative activity by phototautomerization of
      anthrylphenols.
AB  - An antiproliferative investigation was conducted on 3 human cancer cell lines,
      HCT 116 (colon), MCF-7 (breast), and H 460 (lung), on a series of 4
      anthrylphenols in the dark and upon exposure to light (350 nm). 9-(2
      Hydroxyphenyl)anthracene (1) moderately inhibited proliferation, but irradiation
      considerably enhanced the effect. The other anthracenes 4-6 exhibited
      antiproliferative activity in the dark, which was not enhanced upon irradiation.
      The enhancement of the antiproliferative effect on the irradiation of 1 was
      rationalized as being due to the formation of quinone methide (QM 2) by excited
      state proton transfer. QM 2 acts as an electrophilic species capable of reacting
      with biological molecules. Although QM 2 reacts with nucleotides, the adducts
      could not be isolated. On the contrary, cysteine adduct 8 was isolated and
      characterized, whereas the adducts with glycine, serine and tripeptide
      glutathione were characterized by MS. Non-covalent binding of 1 to DNA and bovine
      serum albumin was demonstrated by UV-vis, fluorescence and CD spectroscopy.
      However, a straightforward conclusion regarding the DNA or protein alkylating
      (damaging) ability of 2 could not be drawn. The results obtained by the
      irradiation of 1 in the presence of DNA, amino acids and peptides, cell cycle
      perturbation analysis, and in vitro translation of GFP suggest that the effect is
      not only due to the damage of DNA but also due to the impact on the cellular
      proteins. Considering that to date all QM agents were assumed to target DNA
      dominantly, this is an important finding with an impact on the further
      development of anticancer agents based on QMs.

PMID- 25850015
TI  - Correction: positive effects of bFGF modified rat amniotic epithelial cells
      transplantation on transected rat optic nerve.

PMID- 25850016
TI  - A stable chimeric fibroblast growth factor (FGF) can successfully replace basic
      FGF in human pluripotent stem cell culture.
AB  - Fibroblast growth factors (FGFs) are essential for maintaining self-renewal in
      human embryonic stem cells and induced pluripotent stem cells. Recombinant basic
      FGF (bFGF or FGF2) is conventionally used to culture pluripotent stem cells;
      however, because of the instability of bFGF, repeated addition of fresh bFGF into
      the culture medium is required in order to maintain its concentration. In this
      study, we demonstrate that a heat-stable chimeric variant of FGF, termed FGFC,
      can be successfully used for maintaining human pluripotent stem cells. FGFC is a
      chimeric protein composed of human FGF1 and FGF2 domains that exhibits higher
      thermal stability and protease resistance than do both FGF1 and FGF2. Both human
      embryonic stem cells and induced pluripotent stem cells were maintained in
      ordinary culture medium containing FGFC instead of FGF2. Comparison of cells
      grown in FGFC with those grown in conventional FGF2 media showed no significant
      differences in terms of the expression of pluripotency markers, global gene
      expression, karyotype, or differentiation potential in the three germ lineages.
      We therefore propose that FGFC may be an effective alternative to FGF2, for
      maintenance of human pluripotent stem cells. 

PMID- 25850017
TI  - HATCH score in the prediction of new-onset atrial fibrillation after catheter
      ablation of typical atrial flutter.
AB  - BACKGROUND: New-onset atrial fibrillation (AF) is not uncommon after ablation of
      typical atrial flutter (AFL); however, limited data are available for a risk
      prediction model for the future occurrence of AF in patients with typical AFL
      undergoing successful catheter ablation. OBJECTIVE: This study aimed to determine
      whether the HATCH score (which is based on hypertension, age >=75 years,
      transient ischemic attack or stroke, chronic obstructive pulmonary disease, and
      heart failure) is useful for risk prediction of subsequent AF after ablation of
      typical AFL. METHODS: A total of 216 consecutive patients presenting with typical
      AFL and no history of AF who underwent successful catheter ablation were enrolled
      in the study. The clinical endpoint was occurrence of new-onset AF during follow
      up after ablation. RESULTS: During a follow-up period of 29.1 +/- 18.3 months, 85
      patients (39%) experienced at least 1 episode of AF. Multivariate Cox regression
      analysis demonstrated that the HATCH score (hazard ratio 1.784; 95% confidence
      interval 1.352-2.324; P < .001) and left atrial diameter (hazard ratio 1.270; 95%
      confidence interval 1.115-1.426; P < .001) were independently associated with new
      onset AF after typical AFL ablation. The area under the receiver operator
      characteristic curve based on the HATCH score for prediction of new-onset AF was
      0.743. The HATCH score could be used to stratify the patients into 2 groups with
      different incidences of new-onset AF (69% vs 27%, P < .001) at a cutoff value of
      2. CONCLUSIONS: The HATCH score is a useful predictor of new-onset AF after
      typical AFL ablation.

PMID- 25850018
TI  - The Arabidopsis ethylene overproducer mutant eto1-3 displays enhanced freezing
      tolerance.
AB  - Low temperature is one of the most important environmental stresses constraining
      plant development and distribution. Plants have evolved complex adaptive
      mechanisms to face and survive freezing temperatures. Different signaling
      pathways regulating plant response to cold have been described, and some of them
      are mediated by hormones. Recently, we reported that ethylene (ET) acts as a
      positive regulator of plant freezing tolerance through the activation of cold
      induced gene expression, including the CBF-regulon. Here, we present data
      demonstrating that the Arabidopsis ET overproducer mutant eto1-3 has enhanced
      freezing tolerance. Moreover, we also show that this mutant exhibits increased
      accumulation of CBF1, 2 and 3 transcripts, which should account for its tolerant
      phenotype. All these results constitute new genetic evidence supporting an
      important role for ET in plant response to low temperature by mediating the CBF
      dependent signaling pathway. 

PMID- 25850019
TI  - Effectiveness of an oral cholera vaccine campaign to prevent clinically
      significant cholera in Odisha State, India.
AB  - BACKGROUND: A clinical trial conducted in India suggests that the oral cholera
      vaccine, Shanchol, provides 65% protection over five years against clinically
      significant cholera. Although the vaccine is efficacious when tested in an
      experimental setting, policymakers are more likely to use this vaccine after
      receiving evidence demonstrating protection when delivered to communities using
      local health department staff, cold chain equipment, and logistics. METHODS: We
      used a test-negative, case-control design to evaluate the effectiveness of a
      vaccination campaign using Shanchol and validated the results using a cohort
      approach that addressed disparities in healthcare seeking behavior. The campaign
      was conducted by the local health department using existing resources in a
      cholera-endemic area of Puri District, Odisha State, India. All non-pregnant
      residents one year of age and older were offered vaccine. Over the next two
      years, residents seeking care for diarrhea at one of five health facilities were
      asked to enroll following informed consent. Cases were patients seeking treatment
      for laboratory-confirmed V. cholera-associated diarrhea. Controls were patients
      seeking treatment for V. cholerae negative diarrhea. RESULTS: Of 51,488 eligible
      residents, 31,552 individuals received one dose and 23,751 residents received two
      vaccine doses. We identified 44 V. cholerae O1-associated cases and 366 non V.
      cholerae diarrhea controls. The adjusted protective effectiveness for persons
      receiving two doses was 69.0% (95% CI: 14.5% to 88.8%), which is similar to the
      adjusted estimates obtained from the cohort approach. A statistical trend test
      suggested a single dose provided a modicum of protection (33%, test for trend,
      p=0.0091). CONCLUSION: This vaccine was found to be as efficacious as the results
      reported from a clinical trial when administered to a rural population using
      local health personnel and resources. This study provides evidence that this
      vaccine should be widely deployed by public health departments in cholera endemic
      areas.

PMID- 25850020
TI  - Targeting of rotavirus VP6 to DEC-205 induces protection against the infection in
      mice.
AB  - Rotavirus (RV) is the primary etiologic agent of severe gastroenteritis in human
      infants. Although two attenuated RV-based vaccines have been licensed to be
      applied worldwide, they are not so effective in low-income countries, and the
      induced protection mechanisms have not been clearly established. Thus, it is
      important to develop new generation vaccines that induce long lasting heterotypic
      immunity. VP6 constitutes the middle layer protein of the RV virion. It is the
      most conserved protein and it is the target of protective T-cells; therefore, it
      is a potential candidate antigen for a new generation vaccine against the RV
      infection. We determined whether targeting the DEC-205 present in dendritic cells
      (DCs) with RV VP6 could induce protection at the intestinal level. VP6 was cross
      linked to a monoclonal antibody (mAb) against murine DEC-205 (alphaDEC-205:VP6),
      and BALB/c mice were inoculated subcutaneously (s.c.) twice with the conjugated
      containing 1.5 MUg of VP6 in the presence of polyinosinic-polycytidylic acid
      (Poly I:C) as adjuvant. As controls and following the same protocol, mice were
      immunized with ovalbumin (OVA) cross-linked to the mAb anti-DEC-205 (alphaDEC
      205:OVA), VP6 cross-linked to a control isotype mAb (Isotype:VP6), 3 MUg of VP6
      alone, Poly I:C or PBS. Two weeks after the last inoculation, mice were orally
      challenged with a murine RV. Mice immunized with alpha-DEC-205:VP6 and VP6 alone
      presented similar levels of serum Abs to VP6 previous to the virus challenge.
      However, after the virus challenge, only alpha-DEC-205:VP6 induced up to a 45%
      IgA-independent protection. Memory T-helper (Th) cells from the spleen and the
      mesenteric lymph node (MLN) showed a Th1-type response upon antigen stimulation
      in vitro. These results show that when VP6 is administered parenterally targeting
      DEC-205, it can induce protection at the intestinal level at a very low dose, and
      this protection may be Th1-type cell dependent.

PMID- 25850021
TI  - Increasing influenza vaccination in New York City taxi drivers: A community
      driven approach.
AB  - The Healthy People 2020 influenza immunization goal is 80% for non
      institutionalized adults 18-64. However, vaccination rates remain stubbornly low.
      Culturally tailored approaches to communities with poor vaccine uptake are
      necessary. Taxi drivers are at risk for influenza and its complications, could
      serve as vectors for influenza infection, and could be an effective vaccination
      target to enhance herd immunity of the urban population. To the best of our
      knowledge, this is the first study related to influenza vaccination among taxi
      drivers. The NYC Taxi Network surveyed a convenience sample of 53 taxi drivers to
      understand vaccination barriers. Only 17% had been vaccinated. Results informed a
      pilot tailored workplace intervention, which resulted in vaccinations for 44% of
      unvaccinated drivers. The study revealed that older drivers were more likely to
      be vaccinated than younger drivers, while the most common barrier to immunization
      was that drivers thought vaccination was 'not necessary'. 

PMID- 25850022
TI  - Evaluation of anthrax vaccine safety in 18 to 20 year olds: A first step towards
      age de-escalation studies in adolescents.
AB  - BACKGROUND/OBJECTIVES: Anthrax vaccine adsorbed (AVA, BioThrax((r))) is
      recommended for post-exposure prophylaxis administration for the US population in
      response to large-scale Bacillus anthracis spore exposure. However, no
      information exists on AVA use in children and ethical barriers exist to
      performing pre-event pediatric AVA studies. A Presidential Ethics Commission
      proposed a potential pathway for such studies utilizing an age de-escalation
      process comparing safety and immunogenicity data from 18 to 20 year-olds to older
      adults and if acceptable proceeding to evaluations in younger adolescents. We
      conducted exploratory summary re-analyses of existing databases from 18 to 20
      year-olds (n=74) compared to adults aged 21 to 29 years (n=243) who participated
      in four previous US government funded AVA studies. METHODS: Data extracted from
      studies included elicited local injection-site and systemic adverse events (AEs)
      following AVA doses given subcutaneously at 0, 2, and 4 weeks. Additionally,
      proportions of subjects with >=4-fold antibody rises from baseline to post-second
      and post-third AVA doses (seroresponse) were obtained. RESULTS: Rates of any
      elicited local AEs were not significantly different between younger and older age
      groups for local events (79.2% vs. 83.8%, P=0.120) or systemic events (45.4% vs.
      50.5%, P=0.188). Robust and similar proportions of seroresponses to vaccination
      were observed in both age groups. CONCLUSIONS: AVA was safe and immunogenic in 18
      to 20 year-olds compared to 21 to 29 year-olds. These results provide initial
      information to anthrax and pediatric specialists if AVA studies in adolescents
      are required.

PMID- 25850024
TI  - The effects of video-game training on broad cognitive transfer in multiple
      sclerosis: A pilot randomized controlled trial.
AB  - BACKGROUND: Multiple sclerosis (MS) is a neurodegenerative disease of the central
      nervous system that results in diffuse nerve damage and associated physical and
      cognitive impairments. Of the few comprehensive rehabilitation options that exist
      for populations with lower baseline cognitive functioning, those that have been
      successful at eliciting broad cognitive improvements have focused on a multimodal
      training approach, emphasizing complex cognitive processing that utilizes
      multiple domains simultaneously. METHOD: The current study sought to determine
      the feasibility of an 8-week, hybrid-variable priority training (HVT) program,
      with a secondary aim to assess the success of this training paradigm at eliciting
      broad cognitive transfer effects. Capitalizing on the multimodal training
      modalities offered by the Space Fortress platform, we compared the HVT strategy
      based intervention with a waitlist control group, to primarily assess skill
      acquisition and secondarily determine presence of cognitive transfer. Twenty
      eight participants met inclusionary criteria for the study and were randomized to
      either training or waitlist control groups. To assess broad transfer effects, a
      battery of neuropsychological tests was administered pre- and post-intervention.
      RESULTS: The results indicated an overall improvement in skill acquisition and
      evidence for the feasibility of the intervention, but a lack of broad transfer to
      tasks of cognitive functioning. Participants in the training group, however, did
      show improvements on a measure of spatial short-term memory. CONCLUSIONS: The
      current investigation provided support for the feasibility of a multimodal
      training approach, using the HVT strategy, within the MS population, but lacked
      broad transfer to multiple domains of cognitive functioning. Future improvements
      to obtain greater cognitive transfer efficacy would include a larger sample size,
      a longer course of training to evoke greater game score improvement, the
      inclusion of only cognitively impaired individuals, and integration of subjective
      measures of improvement in addition to objective tests of cognitive performance.

PMID- 25850025
TI  - Profiles of 21-Carbon Steroids in 21-hydroxylase Deficiency.
AB  - CONTEXT: Marked elevations of 17-hydroxyprogesterone (17OHP) are characteristic
      of classic 21-hydroxylase deficiency (21OHD). Testing of 17OHP provides the basis
      for 21OHD diagnosis, although it suffers from several pitfalls. False-positive or
      false-negative results and poor discrimination of nonclassic 21OHD from carriers
      limit the utility of serum 17OHP and necessitate dynamic testing after
      cosyntropin stimulation when values are indeterminate. OBJECTIVE: The objective
      was to provide a detailed characterization of 21-carbon (C21) steroids in classic
      21OHD, which might identify other candidate steroids that could be employed for
      the diagnosis of 21OHD. SETTING AND PARTICIPANTS: Patients (11 women, 10 men)
      with classic 21OHD and 21 sex- and age-matched controls seen in a tertiary
      referral center were studied. METHODS: C21 steroids in the peripheral sera from
      all subjects, as well as in media from cultured testicular adrenal rest tumor
      (TART) cells and normal adrenal (NA) cells, were analyzed using liquid
      chromatography/tandem mass spectrometry (10 steroids). Additionally, the dynamics
      of C21 steroid metabolism in TART and NA cells were assessed with radiotracer
      studies. RESULTS: Five C21 steroids were significantly higher in 21OHD patients:
      17OHP (67-fold; P < .01), 21-deoxycortisol (21dF; 35-fold; P < .01), 16alpha
      hydroxyprogesterone (16OHP; 28-fold; P < .01), progesterone (2-fold; P < .01),
      and 11beta-hydroxyprogesterone (11OHP; not detected in controls; P < .01). The
      same steroids were the highest in media from TART cells relative to the NA cells:
      11OHP, 58- to 65-fold; 21dF, 30- to 41-fold; 17OHP, 9-fold; progesterone, 9- to
      12-fold; and 16OHP, 7-fold. CONCLUSION: Measurement of 16OHP and 11OHP along with
      17OHP and 21dF by liquid chromatography/tandem mass spectrometry might comprise a
      biomarker panel to accurately diagnose all forms of 21OHD.

PMID- 25850026
TI  - Measuring Estrogen Exposure and Metabolism: Workshop Recommendations on Clinical
      Issues.

PMID- 25850027
TI  - Discovery of a P450-catalyzed step in vindoline biosynthesis: a link between the
      aspidosperma and eburnamine alkaloids.
AB  - Here we report the discovery of a cytochrome P450 that is required for the
      biosynthesis of vindoline, a plant-derived natural product used for semi
      synthesis of several anti-cancer drugs. This enzyme catalyzes the formation of an
      epoxide that can undergo rearrangement to yield the vincamine-eburnamine
      backbone, thereby providing evidence for the long-standing hypothesis that the
      aspidosperma- and eburnamine-type alkaloids are biosynthetically related. 

PMID- 25850028
TI  - Adenovirus-mediated transfer of the SOCS-1 gene to mouse lung confers protection
      against hyperoxic acute lung injury.
AB  - Suppressor of cytokine signaling-1 (SOCS-1) is a member of the suppressor of
      cytokine signaling family of proteins and an inhibitor of interleukin-6 (IL-6)
      signaling. SOCS-1 has been shown to protect cells from cellular damage and
      apoptosis induced by tumor necrosis factor (TNF), lipopolysaccharide (LPS), and
      interferon gamma (IL-gamma). However, it is not known whether increased SOCS-1 is
      protective during pulmonary oxidative stress. Therefore, we hypothesized that
      increased SOCS-1 in the lungs of mice would be protective in the setting of
      hyperoxic lung injury. We administered SOCS-1 adenovirus (Ad-SOCS-1)
      intratracheally into the lungs and exposed the mice to 100% O2. Mice infected
      with GFP adenovirus (Ad-GFP) were used as controls. Mice treated with Ad-SOCS-1
      had enhanced survival in 100% oxygen compared to Ad-GFP-administered mice. After
      3 days of hyperoxia, Ad-GFP mice were ill and tachypnic and died after 4 days. In
      contrast, all Ad-SOCS-1-treated mice survived for at least 6 days in hyperoxia
      and 80% survived beyond 7 days. Ad-SOCS-1 transfection protected mouse lungs from
      injury as indicated by lower lung wet/dry weight, alveolar-capillary protein
      leakage, reduced infiltration of inflammatory cells, and lower content of
      thiobarbituric acid-reactive substances in lung homogenate. Our results also
      indicated that Ad-SOCS-1 significantly inhibits hyperoxia-induced ASK-1
      (apoptosis signal-regulating kinase 1) expression. Taken together, these findings
      show that increased expression of adenovirus-mediated SOCS-1 in the lungs of mice
      significantly protects against hyperoxic lung injury. 

PMID- 25850029
TI  - Treatment of near-infrared photodynamic therapy using a liposomally formulated
      indocyanine green derivative for squamous cell carcinoma.
AB  - INTRODUCTION: Photodynamic therapy (PDT) is a less invasive option for cancer
      treatment that has evolved through recent developments in nanotechnology. We have
      designed and synthesized a novel liposome system that includes an indocyanine
      green (ICG) derivative, ICG-C18, in its bilayer. In addition to its use as an
      optical imager to visualize blood, lymphatic, and bile flow, ICG has also been
      used as an optical sensitizer. In the present report, we evaluate the use of our
      novel liposome system, LP-ICG-C18, in PDT for squamous cell carcinoma in an
      autologous murine model. MATERIALS AND METHODS: An excitation pulse beam (300
      MUJ/pulse) of a single band (800 nm) was used for sensitization. The cytotoxicity
      of the photodynamic therapy was evaluated in terms of cellular morphology
      changes, methyl thiazolyl tetrazolium (MTT) assay results, and terminal
      deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end
      labeling (TUNEL) staining. We tested the enhanced permeability and retention
      effect of LP-ICG-C18 in tumor-bearing C3H/He mice using a near-infrared
      fluorescence imaging system and fluorescence microscopy. We also examined the
      antitumor effect of PDT by measuring tumor volume in tumor-bearing mice. RESULTS:
      Cell death and apoptosis were only observed in the PDT group receiving LP-ICG
      C18. LP-ICG-C18 itself had no cytotoxic activity and showed good
      biocompatibility. LP-ICG-C18 accumulated on the tumor 24 hours after injection
      and was retained for approximately 3 weeks. Tumor cell apoptosis following PDT
      with LP-ICG-C18 was also observed under optical microscopy, MTT assay, and TUNEL
      staining. CONCLUSION: These findings suggest that LP-ICG-C18 may be an effective
      intervening material in PDT for malignant disease.

PMID- 25850030
TI  - A prospective randomized evaluation of a pharmacogenomic approach to antiplatelet
      therapy among patients with ST-elevation myocardial infarction: the RAPID STEMI
      study.
AB  - Treatment of carriers of the CYP2C19*2 allele and ABCB1 TT genotype with
      clopidogrel is associated with increased ischemic complications after
      percutaneous coronary intervention (PCI). We sought to evaluate a pharmacogenomic
      strategy among patients undergoing PCI for ST-elevation myocardial infarction
      (STEMI), by performing a randomized trial, enrolling 102 patients. Point-of-care
      genetic testing for CYP2C19*2, ABCB1 TT and CYP2C19*17 was performed with
      carriers of either the CYP2C19*2 allele or ABCB1 TT genotype randomly assigned to
      a strategy of prasugrel 10 mg daily or an augmented dosing strategy of
      clopidogrel (150 mg daily for 6 days then 75 mg daily). The primary end point was
      the proportion of at-risk carriers exhibiting high on-treatment platelet
      reactivity (HPR), a marker associated with increased adverse cardiovascular
      events, after 1 month. Fifty-nine subjects (57.8%) were identified as carriers of
      at least one at-risk variant. Treatment with prasugrel significantly reduced HPR
      compared with clopidogrel by P2Y12 reaction unit (PRU) thresholds of >234 (0 vs
      24.1%, P=0.0046) and PRU>208 (3.3 vs 34.5%, P=0.0025). The sensitivity of point
      of-care testing was 100% (95% CI 88.0-100), 100% (86.3-100) and 96.9% (82.0-99.8)
      and specificity was 97.0% (88.5-99.5), 97.1% (89.0-99.5) and 98.5% (90.9-99.9)
      for identifying CYP2C19*2, ABCB1 TT and CYP2C19*17, respectively. Logistic
      regression confirmed carriers as a strong predictor of HPR (OR=6.58, 95% CI 1.24
      34.92; P=0.03). We confirmed that concurrent identification of three separate
      genetic variants in patients with STEMI receiving PCI is feasible at the bedside.
      Among carriers of at-risk genotypes, treatment with prasugrel was superior to an
      augmented dosing strategy of clopidogrel in reducing HPR. 

PMID- 25850031
TI  - Neuronal cell adhesion genes and antidepressant response in three independent
      samples.
AB  - Drug-effect phenotypes in human lymphoblastoid cell lines recently allowed to
      identify CHL1 (cell adhesion molecule with homology to L1CAM), GAP43 (growth
      associated protein 43) and ITGB3 (integrin beta 3) as new candidates for
      involvement in the antidepressant effect. CHL1 and ITGB3 code for adhesion
      molecules, while GAP43 codes for a neuron-specific cytosolic protein expressed in
      neuronal growth cones; all the three gene products are involved in synaptic
      plasticity. Sixteen polymorphisms in these genes were genotyped in two samples
      (n=369 and 90) with diagnosis of major depressive episode who were treated with
      antidepressants in a naturalistic setting. Phenotypes were response, remission
      and treatment-resistant depression. Logistic regression including appropriate
      covariates was performed. Genes associated with outcomes were investigated in the
      Sequenced Treatment Alternatives to Relieve Depression (STAR*D) genome-wide study
      (n=1861) as both individual genes and through a pathway analysis (Reactome and
      String databases). Gene-based analysis suggested CHL1 rs4003413, GAP43 rs283393
      and rs9860828, ITGB3 rs3809865 as the top candidates due to their replication
      across the largest original sample and the STAR*D cohort. GAP43 molecular pathway
      was associated with both response and remission in the STAR*D, with ELAVL4
      representing the gene with the highest percentage of single nucleotide
      polymorphisms (SNPs) associated with outcomes. Other promising genes emerging
      from the pathway analysis were ITGB1 and NRP1. The present study was the first to
      analyze cell adhesion genes and their molecular pathways in antidepressant
      response. Genes and biomarkers involved in neuronal adhesion should be considered
      by further studies aimed to identify predictors of antidepressant response. 

PMID- 25850032
TI  - IL-6-mediated environmental conditioning of defective Th1 differentiation dampens
      antitumour immune responses in old age.
AB  - Decline in immune function and inflammation concomitantly develop with ageing.
      Here we focus on the impact of this inflammatory environment on T cells, and
      demonstrate that in contrast to successful tumour elimination in young mice,
      replenishment of tumour-specific CD4(+) T cells fails to induce tumour regression
      in aged hosts. The impaired antitumour effect of CD4(+) T cells with their
      defective Th1 differentiation in an aged environment is restored by interleukin
      (IL)-6 blockade or IL-6 deficiency. IL-6 blockade also restores the impaired
      ability of CD4(+) T cells to promote CD8(+) T-cell-dependent tumour elimination
      in aged mice, which requires IFN-gamma. Furthermore, IL-6-stimulated production
      of IL-4/IL-21 through c-Maf induction is responsible for impaired Th1
      differentiation. IL-6 also contributes to IL-10 production from CD4(+) T cells in
      aged mice, causing attenuated responses of CD8(+) T cells. These findings suggest
      that IL-6 serves as an extrinsic factor counteracting CD4(+) T-cell-mediated
      immunity against tumour in old age. 

PMID- 25850033
TI  - Genetic variability and evolutionary diversification of membrane ABC transporters
      in plants.
AB  - BACKGROUND: ATP-binding cassette proteins have been recognized as playing a
      crucial role in the regulation of growth and resistance processes in all kingdoms
      of life. They have been deeply studied in vertebrates because of their role in
      drug resistance, but much less is known about ABC superfamily functions in
      plants. RESULTS: Recently released plant genome sequences allowed us to identify
      803 ABC transporters in four vascular plants (Oryza. sativa, Solanum
      lycopersicum, Solanum tuberosum and Vitis vinifera) and 76 transporters in the
      green alga Volvox carteri, by comparing them with those reannotated in
      Arabidopsis thaliana and the yeast Saccharomyces cerevisiae. Retrieved proteins
      have been phylogenetically analysed to infer orthologous relationships. Most
      orthologous relationships in the A, D, E and F subfamilies were found, and
      interesting expansions within the ABCG subfamily were observed and discussed. A
      high level of purifying selection is acting in the five ABC subfamilies A, B, C,
      D and E. However, evolutionary rates of recent duplicate genes could influence
      vascular plant genome diversification. The transcription profiles of ABC genes
      within tomato organs revealed a broad functional role for some transporters and a
      more specific activity for others, suggesting the presence of key ABC regulators
      in tomato. CONCLUSIONS: The findings achieved in this work could contribute to
      address several biological questions concerning the evolution of the relationship
      between genomes of different species. Plant ABC protein inventories obtained
      could be a valuable tool both for basic and applied studies. Indeed,
      interpolation of the putative role of gene functions can accelerate the
      discovering of new ABC superfamily members.

PMID- 25850035
TI  - Standardization of Nanoparticle Characterization: Methods for Testing Properties,
      Stability, and Functionality of Edible Nanoparticles.
AB  - There has been a rapid increase in the fabrication of various kinds of edible
      nanoparticles for oral delivery of bioactive agents, such as those constructed
      from proteins, carbohydrates, lipids, and/or minerals. It is currently difficult
      to compare the relative advantages and disadvantages of different kinds of
      nanoparticle-based delivery systems because researchers use different analytical
      instruments and protocols to characterize them. In this paper, we briefly review
      the various analytical methods available for characterizing the properties of
      edible nanoparticles, such as composition, morphology, size, charge, physical
      state, and stability. This information is then used to propose a number of
      standardized protocols for characterizing nanoparticle properties, for evaluating
      their stability to environmental stresses, and for predicting their biological
      fate. Implementation of these protocols would facilitate comparison of the
      performance of nanoparticles under standardized conditions, which would
      facilitate the rational selection of nanoparticle-based delivery systems for
      different applications in the food, health care, and pharmaceutical industries. 

PMID- 25850034
TI  - Anti-influenza neuraminidase inhibitor oseltamivir phosphate induces canine
      mammary cancer cell aggressiveness.
AB  - Oseltamivir phosphate is a widely used anti-influenza sialidase inhibitor.
      Sialylation, governed by sialyltransferases and sialidases, is strongly
      implicated in the oncogenesis and progression of breast cancer. In this study we
      evaluated the biological behavior of canine mammary tumor cells upon oseltamivir
      phosphate treatment (a sialidase inhibitor) in vitro and in vivo. Our in vitro
      results showed that oseltamivir phosphate impairs sialidase activity leading to
      increased sialylation in CMA07 and CMT-U27 canine mammary cancer cells.
      Surprisingly, oseltamivir phosphate stimulated, CMT-U27 cell migration and
      invasion capacity in vitro, in a dose-dependent manner. CMT-U27 tumors xenograft
      of oseltamivir phosphate-treated nude mice showed increased sialylation, namely
      alpha2,6 terminal structures and SLe(x) expression. Remarkably, a trend towards
      increased lung metastases was observed in oseltamivir phosphate-treated nude
      mice. Taken together, our findings revealed that oseltamivir impairs canine
      mammary cancer cell sialidase activity, altering the sialylation pattern of
      canine mammary tumors, and leading, surprisingly, to in vitro and in vivo
      increased mammary tumor aggressiveness. 

PMID- 25850037
TI  - Rebooting review.

PMID- 25850038
TI  - IDO inhibitors move center stage in immuno-oncology.

PMID- 25850040
TI  - Pfizer's CDK4/6 inhibitor approved for advanced breast cancer.

PMID- 25850042
TI  - Obama catapults patient-empowered Precision Medicine.

PMID- 25850036
TI  - Targeting Cdc20 as a novel cancer therapeutic strategy.
AB  - The Anaphase Promoting Complex (APC, also called APC/C) regulates cell cycle
      progression by forming two closely related, but functionally distinct E3
      ubiquitin ligase sub-complexes, APC(Cdc20) and APC(Cdh1), respectively. Emerging
      evidence has begun to reveal that Cdc20 and Cdh1 have opposing functions in
      tumorigenesis. Specifically, Cdh1 functions largely as a tumor suppressor,
      whereas Cdc20 exhibits an oncogenic function, suggesting that Cdc20 could be a
      promising therapeutic target for combating human cancer. However, the exact
      underlying molecular mechanisms accounting for their differences in tumorigenesis
      remain largely unknown. Therefore, in this review, we summarize the downstream
      substrates of Cdc20 and the critical functions of Cdc20 in cell cycle
      progression, apoptosis, ciliary disassembly and brain development. Moreover, we
      briefly describe the upstream regulators of Cdc20 and the oncogenic role of Cdc20
      in a variety of human malignancies. Furthermore, we summarize multiple
      pharmacological Cdc20 inhibitors including TAME and Apcin, and their potential
      clinical benefits. Taken together, development of specific Cdc20 inhibitors could
      be a novel strategy for the treatment of human cancers with elevated Cdc20
      expression. 

PMID- 25850045
TI  - Nonbrowning GM apple cleared for market.

PMID- 25850047
TI  - Monsanto adds dicamba to its cache to counter weed threat.

PMID- 25850048
TI  - Engineers of scent.
AB  - Companies exploring biotech approaches to flavor and fragrance production must
      navigate challenges in regulations, market dynamics and public perception. Emily
      Waltz investigates.

PMID- 25850049
TI  - Academic partnerships 2014.

PMID- 25850050
TI  - First rounders podcast: Kari Stefansson.

PMID- 25850051
TI  - The quintessence of immunogenicity reporting for biotherapeutics.

PMID- 25850052
TI  - Silence on the relevant literature and errors in implementation.

PMID- 25850053
TI  - Response to letter of correspondence - Bastiaens et al.

PMID- 25850054
TI  - Opportunities for drug repositioning from phenome-wide association studies.

PMID- 25850055
TI  - Are the gene-patent storm clouds dissipating? A global snapshot.
AB  - In genetic diagnostics testing, what are the boundaries of the global patent
      problem, and is there a real risk that patents and licensing practices could
      impede access to tests?

PMID- 25850057
TI  - Improving reference epigenome catalogs by computational prediction.

PMID- 25850058
TI  - A dynamic picture of protein behavior in cells.

PMID- 25850059
TI  - Genetic variation and alternative splicing.

PMID- 25850061
TI  - Federalist principles for healthcare data networks.
AB  - Applying federalist principles to networked health record data could facilitate
      realization of the potential of shared health data.

PMID- 25850062
TI  - Corrigendum: Network deconvolution as a general method to distinguish direct
      dependencies in networks.

PMID- 25850063
TI  - Expanding ELSI to all areas of innovative science and technology.
AB  - New curricula in the study of the ethical, legal and social implications of
      scientific research aims to further the conversation among all stakeholders in
      the interactions between science, technology and society.

PMID- 25850065
TI  - Photoluminescent silicon nanocrystal-polymer hybrid materials via surface
      initiated reversible addition-fragmentation chain transfer (RAFT) polymerization.
AB  - Silicon-polymer core-shell hybrid materials are obtained via surface initiated
      reversible addition-fragmentation chain transfer (RAFT) polymerization from
      photoluminescent silicon nanocrystals (SiNCs). Polymer grafted SiNCs and free
      polymers in solution are separated using ultracentrifugation. The polymerization
      on the surface proceeds in a living manner which is confirmed via GPC, DLS and
      TGA measurements. This method was applied to various other monomers. The obtained
      materials all show bright red photoluminescence originating from the SiNC core. 

PMID- 25850067
TI  - A method for improving the pose accuracy of a robot manipulator based on multi
      sensor combined measurement and data fusion.
AB  - An improvement method for the pose accuracy of a robot manipulator by using a
      multiple-sensor combination measuring system (MCMS) is presented. It is composed
      of a visual sensor, an angle sensor and a series robot. The visual sensor is
      utilized to measure the position of the manipulator in real time, and the angle
      sensor is rigidly attached to the manipulator to obtain its orientation. Due to
      the higher accuracy of the multi-sensor, two efficient data fusion approaches,
      the Kalman filter (KF) and multi-sensor optimal information fusion algorithm
      (MOIFA), are used to fuse the position and orientation of the manipulator. The
      simulation and experimental results show that the pose accuracy of the robot
      manipulator is improved dramatically by 38%~78% with the multi-sensor data
      fusion. Comparing with reported pose accuracy improvement methods, the primary
      advantage of this method is that it does not require the complex solution of the
      kinematics parameter equations, increase of the motion constraints and the
      complicated procedures of the traditional vision-based methods. It makes the
      robot processing more autonomous and accurate. To improve the reliability and
      accuracy of the pose measurements of MCMS, the visual sensor repeatability is
      experimentally studied. An optimal range of 1 x 0.8 x 1 ~ 2 x 0.8 x 1 m in the
      field of view (FOV) is indicated by the experimental results.

PMID- 25850066
TI  - Difference in the electromyographic onset of the deep and superficial multifidus
      during shoulder movement while standing.
AB  - Based on the current literature, it remains unclear whether electromyographic
      onset of the deep fibers of the multifidus (DM) is dependent on the direction of
      shoulder movement and the position of the center of foot pressure (CFP). In the
      present study, we re-examined the electromyographic onset of the DM during
      shoulder flexion and extension and investigated the influence of the CFP position
      before arm movement. Intramuscular and surface electrodes recorded the
      electromyographic onset of the DM, superficial fibers of the multifidus (SM),
      rectus abdominis, and anterior and posterior deltoid. Eleven healthy participants
      performed rapid, unilateral shoulder flexion and extension in response to audio
      stimuli at three CFP positions: quiet standing, extreme forward leaning, and
      extreme backward leaning. It was found that the electromyographic onset of the DM
      and SM relative to the deltoid was dependent on the direction of arm movement.
      Additionally, of all electromyographic onsets recorded, only that of the DM
      occurred earlier in the extreme forward leaning position than in the extreme
      backward leaning position during shoulder flexion. These results suggest that the
      electromyographic onset of DM was influenced by the biomechanical disturbance
      such as shoulder movement and CFP position. 

PMID- 25850068
TI  - Fast video encryption using the H.264 error propagation property for smart mobile
      devices.
AB  - In transmitting video data securely over Video Sensor Networks (VSNs), since
      mobile handheld devices have limited resources in terms of processor clock speed
      and battery size, it is necessary to develop an efficient method to encrypt video
      data to meet the increasing demand for secure connections. Selective encryption
      methods can reduce the amount of computation needed while satisfying high-level
      security requirements. This is achieved by selecting an important part of the
      video data and encrypting it. In this paper, to ensure format compliance and
      security, we propose a special encryption method for H.264, which encrypts only
      the DC/ACs of I-macroblocks and the motion vectors of P-macroblocks. In
      particular, the proposed new selective encryption method exploits the error
      propagation property in an H.264 decoder and improves the collective performance
      by analyzing the tradeoff between the visual security level and the processing
      speed compared to typical selective encryption methods (i.e., I-frame, P-frame
      encryption, and combined I-/P-frame encryption). Experimental results show that
      the proposed method can significantly reduce the encryption workload without any
      significant degradation of visual security. 

PMID- 25850069
TI  - Simulation methods for solvent vapor annealing of block copolymer thin films.
AB  - Recent progress in modelling the solvent vapor annealing of thin film block
      copolymers is examined in the context of a self-consistent field theory
      framework. Key control variables in determining the final microdomain
      morphologies include swelling ratio or swollen film solvent volume fraction,
      swollen film thickness, substrate and vapor atmosphere surface energies,
      effective volume fraction, and effective Flory-Huggins interaction parameter. The
      regime of solvent vapor annealing studied is where the block copolymer has a high
      enough Flory-Huggins parameter that ordered structures form during swelling and
      are then trapped in the system through quenching. Both implicit and explicit
      consideration of the solvent vapor is considered to distinguish the cases in
      which solvent vapor leads to a non-bulk morphology. Block-selective solvents are
      considered based on the experimental systems of polystyrene-b
      polydimethylsiloxane annealed with toluene and heptane. The results of these
      simulations are compared with these experiments. 

PMID- 25850070
TI  - Use of Historical Case Duration Data for Estimating the Duration of Future Cases.

PMID- 25850071
TI  - Adolescent Endometriosis: Report of a Series of 55 Cases With a Focus on Clinical
      Presentation and Long-Term Issues.
AB  - STUDY OBJECTIVE: To report the clinical presentation and long-term issues of
      adolescent endometriosis. DESIGN: Retrospective cohort study. SETTING: Single
      private clinical center, Bordeaux, France. PATIENTS: Adolescents with a confirmed
      diagnosis of endometriosis. INTERVENTIONS: Surgical excision or ablation or
      lesions performed at laparoscopy. MEASUREMENTS AND MAIN RESULTS: Fifty-five
      adolescents, ages from 12 to 19 years (mean age 17.8), who were diagnosed with
      endometriosis from March 1998 to April 2013 were included in the study. Pain of
      various types was the leading symptom in all patients, except 2. Twenty-three
      patients had an adnexal mass identified preoperatively, and 5 had an associated
      infertility issue at the time of diagnostic laparoscopy. Four patients had an
      associated genital malformation. Fifty-one percent of the patients had a history
      of appendectomy. A familial history of endometriosis was reported by 19 patients
      (34.5%), with a first-degree relative affected in 14 cases (25.45%), and 47.3% of
      patients were smoking at least 5 cigarettes a day. Superficial implants was
      encountered in 31 cases (56.4%), endometriomas in 18 cases (32.72%), and deep
      infiltrating endometriosis (DIE) in 6 cases (10.90%). Sixty percent of patients
      were scored as stages I to II and 40% as stages III to IV. Five patients were
      lost to follow-up, and 37 had a follow-up ranging from 36 to 315 months (mean
      follow-up 125.5 months). Among the 50 patients not lost to follow-up, 13 (26%)
      had either no pain, or improved and had acceptable pain with medical treatment.
      Seventeen patients of the 50 adolescents not lost to follow-up (34%) underwent a
      repeat laparoscopy. A subsequent laparoscopic and/or magnetic resonance imaging
      scan was performed in 35 patients because of persistent pain. Among these, there
      was 12 endometriomas (7 recurrences) and 12 DIEs (3 recurrences), giving
      recurrence rates for endometriomas and DIEs of 36.84% and 50%, respectively.
      During the study, 18 patients wished to have a child. Thirteen had a delivery
      (72.2%), and 9 pregnancies occurred in patients who initially presented with
      stage I to II endometriosis. Of the 11 patients who had subfertility, 6
      successfully conceived (54.5%). CONCLUSIONS: Adolescent endometriosis is not a
      rare condition. In our study a familial history was reported in more than one
      third of patients. Among those patients treated for DIE, there was a trend for
      higher rates of recurrences (symptoms or lesions) that required repeat
      laparoscopy. However, the impact on subsequent fertility appeared to have been
      limited.

PMID- 25850072
TI  - Reply: To PMID 25020086.

PMID- 25850074
TI  - The synergistic mechanism of graphene and MoS2 for hydrogen generation: insights
      from density functional theory.
AB  - The synergistic effect of graphene and MoS2 was investigated by using density
      functional theory (DFT) calculations on the enhanced photocatalytic H2 production
      activity of TiO2/graphene/MoS2 ternary nanoparticles. Our results indicate that
      it can form a weak covalent bond between the Ti atom of TiO2 nanocluster and the
      nearest C atom on graphene, which not only makes the original degenerate C(2p)
      orbital level of the graphene (part of the conduction band energy level) split,
      resulting in the production of a lower level of C(2p) that makes it easier to
      accept the excited electron from the Ti(3d) orbital, but also forms a +/-
      sequence electric field in the interface between them. It is conclusive that the
      electron moves from the TiO2 cluster to the graphene. In addition, we also find
      that the band gap of the TiO2 cluster can be doped by the graphene and MoS2, and
      the conduction band consists predominantly of C(2p), S(3p) and Mo(4d) orbital
      energy level near the Fermi level. These results illustrate that the excited
      electron will eventually accumulate in the graphene or MoS2 film, which can
      effectively enhance the separation between the excited electrons and the holes in
      the TiO2 clusters, thereby increasing the efficiency of hydrogen evolution. Our
      results are consistent with the experimental results, and can provide some
      valuable information for the design of photocatalytic composites. 

PMID- 25850073
TI  - Laparoscopic Ureteroneocystostomy: Be Prepared!
AB  - STUDY OBJECTIVE: To assess the outcomes and complications of laparoscopic
      ureteroneocystotomy in gynecologic surgery. DESIGN: We retrospectively reviewed
      all medical records of patients who underwent ureteroneocystostomy between April
      2008 and May 2012. DESIGN CLASSIFICATION: Retrospective case series study.
      SETTING: A university tertiary care hospital. PATIENTS: Nine patients underwent
      ureteroneocystostomy: 3 patients had ureteral endometriosis stenoses; and 6
      patients had iatrogenic ureter injuries. INTERVENTIONS: All procedures were
      performed laparoscopically. The ureterovesical re-implantation was unilateral in
      8 cases and bilateral for 1 patient. MEASUREMENTS AND MAIN RESULTS: The mean
      operating time was 226.7 min (range, 120-480). Average blood loss was 114.4 mL
      (range, 30-400). The mean duration of the in-dwelling catheter was 10.4 days
      (range, 7-21); the average hospital stay was 12.6 days (range, 6-26). The mean
      duration of the ureteral double J stent was 7.8 weeks (range, 6-16). One patient
      was re-operated for vaginal and laparoscopic drainage of a pelvic abscess on the
      sixth postoperative day. The median follow-up time was 20.8 months (range, 9-36),
      No patient had stenosis or breakdown of a suture line. CONCLUSIONS: Our series
      confirms the feasibility and the effectiveness of laparoscopic
      ureteroneocystostomy. This minimally invasive approach, which avoids laparotomy,
      requires a multidisciplinary team.

PMID- 25850075
TI  - The use of rat spinal reflexes to quantify injection pain.
AB  - Pain caused by subcutaneous injections is unpleasant, which may limit patient
      compliance. The objective of this study was to use spinal reflexes to quantify
      subcutaneous injection pain. Spinal reflexes were measured using an
      electromyogram (EMG) test. The effects of injection volume, pH and osmotic
      pressure were investigated. The EMG responses increased with injection volume and
      the acidity of the solution but did not depend on the osmotic pressure of the
      solution. The EMG responses differed for subcutaneously injected sodium chloride
      and glucose over the same range of osmotic pressures. Pain caused by the
      subcutaneous injections was unrelated to the osmotic ratio up to approximately 5.
      The injection pain caused by therapeutic protein solutions was also evaluated. We
      compared the EMG responses of the adalimumab and etanercept, as the injection of
      adalimumab is more painful than that of etanercept in humans. The EMG magnitude
      for adalimumab was twice that induced by etanercept as observed for the EMG tests
      performed in rats. Therapeutic proteins account for an increasingly large
      proportion of pharmaceutical drugs. When a high dose of therapeutic proteins is
      required, the protein solution must often be highly concentrated to reduce the
      injection volume. For patient comfort, it is critical to reduce injection pain.
      The EMG test reported here allows subcutaneous injection pain to be quantified
      and may be useful for optimizing drug formulations. 

PMID- 25850076
TI  - Tamoxifen-dependent, inducible Bmp2CreER drives selective recombinase activity in
      early interdigital mesenchyme and digit collateral ligaments.
AB  - During limb development, the interdigital mesenchyme has been proposed to play a
      signaling role instructing morphogenesis of different digit types, as well as
      undergoing programmed cell death necessary to free digits in animals not adapted
      for swimming or flying. We have generated a conditional, tamoxifen-dependent Cre
      line, Bmp2CreER, which drives highly selective recombination restricted to the
      distal limb mesoderm, largely restricted to the interdigits, and selectively
      active in digit ligament but not tendon progenitors at later stages. The
      Bmp2CreER provides a valuable new tool to dissect roles of interdigital
      mesenchyme and potentially investigate divergence of ligament and tendon
      lineages. 

PMID- 25850077
TI  - Models of cortical malformation--Chemical and physical.
AB  - Pharmaco-resistant epilepsies, and also some neuropsychiatric disorders, are
      often associated with malformations in hippocampal and neocortical structures.
      The mechanisms leading to these cortical malformations causing an imbalance
      between the excitatory and inhibitory system are largely unknown. Animal models
      using chemical or physical manipulations reproduce different human pathologies by
      interfering with cell generation and neuronal migration. The model of in utero
      injection of methylazoxymethanol (MAM) acetate mimics periventricular nodular
      heterotopia. The freeze lesion model reproduces (poly)microgyria, focal
      heterotopia and schizencephaly. The in utero irradiation model causes microgyria
      and heterotopia. Intraperitoneal injections of carmustine 1-3-bis-chloroethyl
      nitrosurea (BCNU) to pregnant rats produces laminar disorganization, heterotopias
      and cytomegalic neurons. The ibotenic acid model induces focal cortical
      malformations, which resemble human microgyria and ulegyria. Cortical dysplasia
      can be also observed following prenatal exposure to ethanol, cocaine or
      antiepileptic drugs. All these models of cortical malformations are characterized
      by a pronounced hyperexcitability, few of them also produce spontaneous epileptic
      seizures. This dysfunction results from an impairment in GABAergic inhibition
      and/or an increase in glutamatergic synaptic transmission. The cortical region
      initiating or contributing to this hyperexcitability may not necessarily
      correspond to the site of the focal malformation. In some models wide-spread
      molecular and functional changes can be observed in remote regions of the brain,
      where they cause pathophysiological activities. This paper gives an overview on
      different animal models of cortical malformations, which are mostly used in
      rodents and which mimic the pathology and to some extent the pathophysiology of
      neuronal migration disorders associated with epilepsy in humans. 

PMID- 25850078
TI  - A novel videographic method for quantitatively tracking vibrissal motor recovery
      following facial nerve injuries in rats.
AB  - BACKGROUND: Previous studies of vibrissal movements employ either optoelectronic
      recording techniques in the head fixed rodent, or videographic recordings in
      freely moving animals. However, both approaches have shortcomings for
      quantitatively tracking the process of vibrissal motor recovery. NEW METHOD: A
      critical feature of our videographic method is to measure tagged vibrissae
      movements while leaving all others intact in body restrained rats without head
      fixation. Thirty two adult rats underwent facial nerve manipulation and testing.
      All animals underwent baseline preoperative whisking testing. In the experimental
      groups, the right facial nerve was either crushed, or transected and sutured. In
      the control groups, the left facial nerve underwent either sham surgery, or
      transection denervation. Whisking function was measured for the ensuing 2 to 12
      weeks. Data were analyzed for whisking recovery. RESULTS: Baseline preoperative
      whisking testing showed that majority of free whisking on the both sides is
      synchronous and symmetric, which allows us to compare vibrissal motor data
      between intact and manipulated side after facial nerve injury. As expected, the
      recovery of whisking function following crush is better and earlier than that
      with transection and suture. COMPARISON WITH EXISTING METHOD(S): To our
      knowledge, this novel videographic method is a significant simplification over
      currently employed optoelectronic recording techniques and videographic methods.
      CONCLUSIONS: Our novel videographic method may be a powerful tool to investigate
      motor recovery from facial nerve manipulation in the rat model.

PMID- 25850079
TI  - Activation of 5-HT1A receptors in the preBotzinger region has little impact on
      the respiratory pattern.
AB  - The preBotzinger (preBotC) complex has been suggested as the primary site where
      systemically administered selective serotonin agonists have been shown to reduce
      or prevent opioid-induced depression of breathing. However, this hypothesis has
      not been tested pharmacologically in vivo. This study sought to determine whether
      5-HT1A receptors within the preBotC and ventral respiratory column (VRC) mediate
      the tachypneic response induced by intravenous (IV) (+/-)-8-Hydroxy-2
      diproplyaminotetralin hydrobromide (8-OH-DPAT) in a decerebrated dog model. IV 8
      OH-DPAT (19 +/- 2 MUg/kg) reduced both inspiratory (I) and expiratory (E)
      durations by ~ 40%, but had no effect on peak phrenic activity (PPA).
      Picoejection of 1, 10, and 100 MUM 8-OH-DPAT on I and E preBotC neurons produced
      dose-dependent decreases up to ~ 40% in peak discharge. Surprisingly,
      microinjections of 8-OH-DPAT and 5-HT within the VRC from the obex to 9 mm
      rostral had no effect on timing and PPA. These results suggest that the
      tachypneic effects of IV 8-OH-DPAT are due to receptors located outside of the
      areas we studied.

PMID- 25850080
TI  - Association of the biomarkers soluble ST2, galectin-3 and growth-differentiation
      factor-15 with heart failure and other non-cardiac diseases.
AB  - BACKGROUND: The biomarkers soluble ST2 (sST2), galectin-3, and growth
      differentiation factor-15 (GDF-15) provide prognostic information in patients
      with heart failure (HF). The aim of this study was to evaluate to which extent
      plasma concentrations of these biomarkers are increased in HF compared with
      diverse non-cardiac conditions such as infectious disease or chronic kidney
      disease. METHODS: We recruited 15 patients in each of the following clinical
      categories: HF without co-morbidity, pneumonia without co-morbidity, chronic
      obstructive pulmonary disease (COPD) without co-morbidity, HF and a co-morbidity
      of pneumonia, renal disease without co-morbidity, and sepsis. We used 22 healthy
      individuals as control group. In each of the 112 study participants, we measured
      plasma concentrations of sST2 (Presage assay), galectin-3 (Abbott assay) and GDF
      15 (Roche assay). RESULTS: Compared to controls, the median sST2 concentration
      was ~2.5-fold increased in HF, ~3.5-fold in pneumonia, ~5.0-fold in COPD, ~5.8
      fold in HF+pneumonia, and ~70-fold in sepsis (p<0.001 for all). sST2 was not
      significantly increased in renal disease. Compared to controls, the median
      galectin-3 concentration was ~1.5-fold increased in HF, ~1.4-fold in pneumonia,
      ~2.4-fold in HF+pneumonia, ~2.5-fold in renal disease, and ~2.7-fold in sepsis
      (p<0.001 for all). Galectin-3 was not significantly increased in COPD. Compared
      to controls, the median GDF-15 concentration was ~4.4-fold increased in HF, ~5.4
      fold in pneumonia, ~2.1-fold in COPD, ~8.3-fold in HF+pneumonia, ~5.1-fold in
      renal disease, and ~27-fold in sepsis (p<0.001). In the 112 study participants,
      correlation analyses revealed a relatively strong association between galectin-3
      and GDF-15 (correlation coefficient, 0.739; p<0.001). CONCLUSION: Because
      increased plasma concentrations of sST2, galectin-3, and GDF-15 are not specific
      for a distinct disease group, the three biomarkers are not useful for diagnostic
      purposes. The results of our study are novel with respect to sST2, galectin-3 and
      GDF-15 as markers of inflammatory diseases and should encourage further studies.

PMID- 25850081
TI  - Modeling Implantable Passive Mechanisms for Modifying the Transmission of Forces
      and Movements Between Muscle and Tendons.
AB  - This paper explores the development of biomechanical models for evaluating a new
      class of passive mechanical implants for orthopedic surgery. The proposed
      implants take the form of passive engineered mechanisms, and will be used to
      improve the functional attachment of muscles to tendons and bone by modifying the
      transmission of forces and movement inside the body. Specifically, we present how
      two types of implantable mechanisms may be modeled in the open-source
      biomechanical software OpenSim. The first implant, which is proposed for hand
      tendon-transfer surgery, differentially distributes the forces and movement from
      one muscle across multiple tendons. The second implant, which is proposed for
      knee-replacement surgery, scales up the forces applied to the knee joint by the
      quadriceps muscle. This paper's key innovation is that such mechanisms have never
      been considered before in biomechanical simulation modeling and in surgery. When
      compared with joint function enabled by the current surgical practice of using
      sutures to make the attachment, biomechanical simulations show that the surgery
      with 1) the differential mechanism (tendon network) implant improves the fingers'
      ability to passively adapt to an object's shape significantly during grasping
      tasks (2.74* as measured by the extent of finger flexion) for the same muscle
      force, and 2) the force-scaling implant increases knee-joint torque by 84% for
      the same muscle force. The critical significance of this study is to provide a
      methodology for the design and inclusion of the implants into biomechanical
      models and validating the improvement in joint function they enable when compared
      with current surgical practice. 

PMID- 25850082
TI  - A Dual-Mode Large-Arrayed CMOS ISFET Sensor for Accurate and High-Throughput pH
      Sensing in Biomedical Diagnosis.
AB  - GOAL: The existing ISFET-based DNA sequencing detects hydrogen ions released
      during the polymerization of DNA strands on microbeads, which are scattered into
      microwell array above the ISFET sensor with unknown distribution. However, false
      pH detection happens at empty microwells due to crosstalk from neighboring
      microbeads. In this paper, a dual-mode CMOS ISFET sensor is proposed to have
      accurate pH detection toward DNA sequencing. METHODS: Dual-mode sensing, optical
      and chemical modes, is realized by integrating a CMOS image sensor (CIS) with
      ISFET pH sensor, and is fabricated in a standard 0.18-MUm CIS process. With
      accurate determination of microbead physical locations with CIS pixel by contact
      imaging, the dual-mode sensor can correlate local pH for one DNA slice at one
      location-determined microbead, which can result in improved pH detection
      accuracy. Moreover, toward a high-throughput DNA sequencing, a correlated-double
      sampling readout that supports large array for both modes is deployed to reduce
      pixel-to-pixel nonuniformity such as threshold voltage mismatch. RESULTS: The
      proposed CMOS dual-mode sensor is experimentally examined to show a well
      correlated pH map and optical image for microbeads with a pH sensitivity of 26.2
      mV/pH, a fixed pattern noise (FPN) reduction from 4% to 0.3%, and a readout speed
      of 1200 frames/s. CONCLUSION: A dual-mode CMOS ISFET sensor with suppressed FPN
      for accurate large-arrayed pH sensing is proposed and demonstrated with state-of
      the-art measured results toward accurate and high-throughput DNA sequencing.
      SIGNIFICANCE: The developed dual-mode CMOS ISFET sensor has great potential for
      future personal genome diagnostics with high accuracy and low cost.

PMID- 25850083
TI  - Aliasing Artefact Suppression in Compressed Sensing MRI for Random Phase-Encode
      Undersampling.
AB  - GOAL: Random phase-encode undersampling of Cartesian k-space trajectories is
      widely implemented in compressed sensing (CS) MRI. However, its one-dimensional
      (1-D) randomness inherently introduces large coherent aliasing artefacts along
      the undersampled direction in the reconstruction and, thus, degrades the image
      quality. This paper proposes a novel reconstruction scheme to reduce the 1-D
      undersampling-induced aliasing artefacts. METHODS: The proposed reconstruction
      progress is separated into two steps in our new algorithm. In step one, we
      transfer the original two-dimensional (2-D) image reconstruction into a parallel
      1-D signal reconstruction procedure, which takes advantage of the superior
      incoherence property in the phase direction. In step two, using the new k-space
      data obtained from the 1-D reconstructions, we implement a follow-up 2-D CS
      reconstruction to produce a better solution, which exploits the inherent
      correlations between the adjacent lines of 1-D reconstructed signals. RESULTS: We
      evaluated the performance on various cases of typical MR images, including
      cardiac cine, brain, foot, and angiogram at the reduction factor up to 10 and
      compared the results with the conventional CS method. Experiments using the
      proposed method demonstrated faithful reconstruction of the MR images.
      CONCLUSION: Compared with conventional method, the new method achieves more
      accurate reconstruction results with 2-5 dB gain in peak SNR and higher
      structural similarity index. SIGNIFICANCE: The proposed method improves image
      quality of the reconstructions and suppresses the coherent artefacts introduced
      by the random phase-encode undersampling.

PMID- 25850084
TI  - The Role of Pulse Repetition Rate in nsPEF-Induced Electroporation: A Biological
      and Numerical Investigation.
AB  - The impact of pulse repetition rate (PRR) in modulating electroporation (EP)
      induced by nanosecond pulsed electric fields (nsPEFs) in mammalian cells was
      approached here by performing both biological and numerical analysis. Plasma
      membrane permeabilization and viability of Jurkat cells were analyzed after
      exposure to 500, 1.3 MV/m, 40 ns PEFs with variable PRR (2-30 Hz). A finite
      element model was used to investigate EP dynamics in a single cell under the same
      pulsing conditions, by looking at the time course of transmembrane voltage and
      pore density on the ns time scale. The biological observations showed an
      increased EP and reduced viability of the exposed cells at lower PRR in the
      considered range. The numerical analysis resulted in different dynamics of plasma
      membrane response when ns pulses were delivered with different PRR, consistently
      with a phenomenon of electrodesensitization recently hypothesized by another
      research group.

PMID- 25850085
TI  - Saliency based ulcer detection for wireless capsule endoscopy diagnosis.
AB  - Ulcer is one of the most common symptoms of many serious diseases in the human
      digestive tract. Especially for the ulcers in the small bowel where other
      procedures cannot adequately visualize, wireless capsule endoscopy (WCE) is
      increasingly being used in the diagnosis and clinical management. Because WCE
      generates large amount of images from the whole process of inspection, computer
      aided detection of ulcer is considered an indispensable relief to clinicians. In
      this paper, a two-staged fully automated computer-aided detection system is
      proposed to detect ulcer from WCE images. In the first stage, we propose an
      effective saliency detection method based on multi-level superpixel
      representation to outline the ulcer candidates. To find the perceptually and
      semantically meaningful salient regions, we first segment the image into multi
      level superpixel segmentations. Each level corresponds to different initial
      region sizes of the superpixels. Then we evaluate the corresponding saliency
      according to the color and texture features in superpixel region of each level.
      In the end, we fuse the saliency maps from all levels together to obtain the
      final saliency map. In the second stage, we apply the obtained saliency map to
      better encode the image features for the ulcer image recognition tasks. Because
      the ulcer mainly corresponds to the saliency region, we propose a saliency max
      pooling method integrated with the Locality-constrained Linear Coding (LLC)
      method to characterize the images. Experiment results achieve promising 92.65%
      accuracy and 94.12% sensitivity, validating the effectiveness of the proposed
      method. Moreover, the comparison results show that our detection system
      outperforms the state-of-the-art methods on the ulcer classification task. 

PMID- 25850086
TI  - Bayesian model selection for pathological neuroimaging data applied to white
      matter lesion segmentation.
AB  - In neuroimaging studies, pathologies can present themselves as abnormal intensity
      patterns. Thus, solutions for detecting abnormal intensities are currently under
      investigation. As each patient is unique, an unbiased and biologically plausible
      model of pathological data would have to be able to adapt to the subject's
      individual presentation. Such a model would provide the means for a better
      understanding of the underlying biological processes and improve one's ability to
      define pathologically meaningful imaging biomarkers. With this aim in mind, this
      work proposes a hierarchical fully unsupervised model selection framework for
      neuroimaging data which enables the distinction between different types of
      abnormal image patterns without pathological a priori knowledge. Its application
      on simulated and clinical data demonstrated the ability to detect abnormal
      intensity clusters, resulting in a competitive to improved behavior in white
      matter lesion segmentation when compared to three other freely-available
      automated methods. 

PMID- 25850087
TI  - Multi-dimensional complete ensemble empirical mode decomposition with adaptive
      noise applied to laser speckle contrast images.
AB  - Laser speckle contrast imaging (LSCI) is a noninvasive full-field optical
      technique which allows analyzing the dynamics of microvascular blood flow. LSCI
      has attracted attention because it is able to image blood flow in different kinds
      of tissue with high spatial and temporal resolutions. Additionally, it is simple
      and necessitates low-cost devices. However, the physiological information that
      can be extracted directly from the images is not completely determined yet. In
      this work, a novel multi-dimensional complete ensemble empirical mode
      decomposition with adaptive noise (MCEEMDAN) is introduced and applied in LSCI
      data recorded in three physiological conditions (rest, vascular occlusion and
      post-occlusive reactive hyperaemia). MCEEMDAN relies on the improved complete
      ensemble empirical mode decomposition with adaptive noise (CEEMDAN) and our
      algorithm is specifically designed to analyze multi-dimensional data (such as
      images). Over the recent multi-dimensional ensemble empirical mode decomposition
      (MEEMD), MCEEMDAN has the advantage of leading to an exact reconstruction of the
      original data. The results show that MCEEMDAN leads to intrinsic mode functions
      and residue that reveal hidden patterns in LSCI data. Moreover, these patterns
      differ with physiological states. MCEEMDAN appears as a promising way to extract
      features in LSCI data for an improvement of the image understanding. 

PMID- 25850088
TI  - Sorted consecutive local binary pattern for texture classification.
AB  - In this paper, we propose a sorted consecutive local binary pattern (scLBP) for
      texture classification. Conventional methods encode only patterns whose spatial
      transitions are not more than two, whereas scLBP encodes patterns regardless of
      their spatial transition. Conventional methods do not encode patterns on account
      of rotation-invariant encoding; on the other hand, patterns with more than two
      spatial transitions have discriminative power. The proposed scLBP encodes all
      patterns with any number of spatial transitions while maintaining their rotation
      invariant nature by sorting the consecutive patterns. In addition, we introduce
      dictionary learning of scLBP based on kd-tree which separates data with a space
      partitioning strategy. Since the elements of sorted consecutive patterns lie in
      different space, it can be generated to a discriminative code with kd-tree.
      Finally, we present a framework in which scLBPs and the kd-tree can be combined
      and utilized. The results of experimental evaluation on five texture data sets-
      Outex, CUReT, UIUC, UMD, and KTH-TIPS2-a--indicate that our proposed framework
      achieves the best classification rate on the CUReT, UMD, and KTH-TIPS2-a data
      sets compared with conventional methods. The results additionally indicate that
      only a marginal difference exists between the best classification rate of
      conventional methods and that of the proposed framework on the UIUC and Outex
      data sets.

PMID- 25850089
TI  - Effects of Innovative WALKBOT Robotic-Assisted Locomotor Training on Balance and
      Gait Recovery in Hemiparetic Stroke: A Prospective, Randomized, Experimenter
      Blinded Case Control Study With a Four-Week Follow-Up.
AB  - The present clinical investigation was to ascertain whether the effects of
      WALKBOT-assisted locomotor training (WLT) on balance, gait, and motor recovery
      were superior or similar to the conventional locomotor training (CLT) in patients
      with hemiparetic stroke. Thirty individuals with hemiparetic stroke were randomly
      assigned to either WLT or CLT. WLT emphasized on a progressive, conventional
      locomotor retraining practice (40 min) combined with the WALKBOT-assisted, haptic
      guidance and random variable locomotor training (40 min) whereas CLT involved
      conventional physical therapy alone (80 min). Both intervention dosages were
      standardized and provided for 80 min, five days/week for four weeks. Clinical
      outcomes included function ambulation category (FAC), Berg balance scale (BBS),
      Korean modified Barthel index (K-MBI), modified Ashworth scale (MAS), and EuroQol
      5 dimension (EQ-5D) before and after the four-week program as well as at follow
      up four weeks after the intervention. Two-way repeated measure ANOVA showed
      significant interaction effect (time * group) for FAC (p=0.02), BBS (p=0.03) ,
      and K-MBI (p=0.00) across the pre-training, post-training, and follow-up tests,
      indicating that WLT was more beneficial for balance, gait and daily activity
      function than CLT alone. However, no significant difference in other variables
      was observed. This is the first clinical trial that highlights the superior,
      augmented effects of the WALKBOT-assisted locomotor training on balance, gait and
      motor recovery when compared to the conventional locomotor training alone in
      patients with hemiparetic stroke. 

PMID- 25850090
TI  - EEG-Based Attention Tracking During Distracted Driving.
AB  - Distracted driving might lead to many catastrophic consequences. Developing a
      countermeasure to track drivers' focus of attention (FOA) and engagement of
      operators in dual (multi)-tasking conditions is thus imperative. Ten healthy
      volunteers participated in a dual-task experiment that comprised two tasks: a
      lane-keeping driving task and a mathematical problem-solving task (e.g.,
      24+15=37?) during which their electroencephalogram (EEG) and behaviors were
      concurrently recorded. Independent component analysis (ICA) was employed as a
      spatial filter to separate the contributions of independent sources from the
      recorded EEG data. The power spectra of six components (i.e., frontal, central,
      parietal, occipital, left motor, and right motor) extracted from single-task
      conditions were fed into support vector machine (SVM) based on the radial basis
      function (RBF) kernel to build an FOA assessment system. The system achieved
      84.6+/-5.8% and 86.2+/-5.4% classification accuracies in detecting the
      participants' FOAs on the math versus driving tasks, respectively. This FOA
      assessment system was then applied to evaluate participants' FOAs during dual
      task conditions. The detected FOAs revealed that participants' cognitive
      attention and strategies dynamically changed between tasks to optimize the
      overall performance, as attention was limited and competed. The empirical results
      of this study demonstrate the feasibility of a practical system to continuously
      estimating cognitive attention through EEG spectra.

PMID- 25850092
TI  - Distributed Signal Processing for Wireless EEG Sensor Networks.
AB  - Inspired by ongoing evolutions in the field of wireless body area networks
      (WBANs), this tutorial paper presents a conceptual and exploratory study of
      wireless electroencephalography (EEG) sensor networks (WESNs), with an emphasis
      on distributed signal processing aspects. A WESN is conceived as a modular
      neuromonitoring platform for high-density EEG recordings, in which each node is
      equipped with an electrode array, a signal processing unit, and facilities for
      wireless communication. We first address the advantages of such a modular
      approach, and we explain how distributed signal processing algorithms make WESNs
      more power-efficient, in particular by avoiding data centralization. We provide
      an overview of distributed signal processing algorithms that are potentially
      applicable in WESNs, and for illustration purposes, we also provide a more
      detailed case study of a distributed eye blink artifact removal algorithm.
      Finally, we study the power efficiency of these distributed algorithms in
      comparison to their centralized counterparts in which all the raw sensor signals
      are centralized in a near-end or far-end fusion center.

PMID- 25850091
TI  - The Retinal Response to Sinusoidal Electrical Stimulation.
AB  - Rectangular electrical pulses are the primary stimulus waveform used in retinal
      prosthetics as well as many other neural stimulation applications. Unfortunately,
      the utility of pulsatile stimuli is limited by the inability to avoid the
      activation of passing axons, which can result in the distortion of the spatial
      patterns of elicited neural activity. Because avoiding axons would likely improve
      clinical outcomes, the examination of alternate stimulus waveforms is warranted.
      Here, we studied the response of rabbit retinal ganglion cells (RGCs) to
      sinusoidal electrical stimulation applied at frequencies of 5, 10, 25, and 100
      Hz. Targeted RGCs were restricted to 4 common types: OFF-Brisk Transient, OFF
      Sustained, ON-Brisk Transient, and ON-Sustained. Interestingly, response patterns
      varied between different types; the most notable difference was the relatively
      weak response of ON-Sustained cells to low frequencies. Calculation of total
      spike counts per trial revealed that lower frequencies are more charge efficient
      than high frequencies. Finally, experiments utilizing synaptic blockers revealed
      that 5 and 10 Hz activate photoreceptors while 25 and 100 Hz activate RGCs. Taken
      together, our results suggest that while sinusoidal electrical stimulation may
      provide a useful research tool, its clinical utility may be limited. 

PMID- 25850093
TI  - Further Results on Predictor-Based Control of Neuromuscular Electrical
      Stimulation.
AB  - Electromechanical delay (EMD) and uncertain nonlinear muscle dynamics can cause
      destabilizing effects and performance loss during closed-loop control of
      neuromuscular electrical stimulation (NMES). Linear control methods for NMES
      often perform poorly due to these technical challenges. A new predictor-based
      closed-loop controller called proportional integral derivative controller with
      delay compensation (PID-DC) is presented in this paper. The PID-DC controller was
      designed to compensate for EMDs during NMES. Further, the robust controller can
      be implemented despite uncertainties or in the absence of model knowledge of the
      nonlinear musculoskeletal dynamics. Lyapunov stability analysis was used to
      synthesize the new controller. The effectiveness of the new controller was
      validated and compared with two recently developed nonlinear NMES controllers,
      through a series of closed-loop control experiments on four able-bodied human
      subjects. Experimental results depict statistically significant improved
      performance with PID-DC. The new controller is shown to be robust to variations
      in an estimated EMD value.

PMID- 25850094
TI  - Haptic Shared Control in Tele-Manipulation: Effects of Inaccuracies in Guidance
      on Task Execution.
AB  - Haptic shared control is a promising approach to improve tele-manipulated task
      execution, by making safe and effective control actions tangible through guidance
      forces. In current research, these guidance forces are most often generated based
      on pre-generated, errorless models of the remote environment. Hence such guidance
      forces are exempt from the inaccuracies that can be expected in practical
      implementations. The goal of this research is to quantify the extent to which
      task execution is degraded by inaccuracies in the model on which haptic guidance
      forces are based. In a human-in-the-loop experiment, subjects (n = 14) performed
      a realistic tele-manipulated assembly task in a virtual environment. Operators
      were provided with various levels of haptic guidance, namely no haptic guidance
      (conventional tele-manipulation), haptic guidance without inaccuracies, and
      haptic guidance with translational inaccuracies (one large inaccuracy, in the
      order of magnitude of the task, and a second smaller inaccuracy). The quality of
      natural haptic feedback (i.e., haptic transparency) was varied between high and
      low to identify the operator's ability to detect and cope with inaccuracies in
      haptic guidance. The results indicate that haptic guidance is beneficial for task
      execution when no inaccuracies are present in the guidance. When inaccuracies are
      present, this may degrade task execution, depending on the magnitude and the
      direction of the inaccuracy. The effect of inaccuracies on overall task
      performance is dominated by effects found for the Constrained Translational
      Movement, due to its potential for jamming. No evidence was found that a higher
      quality of haptic transparency helps operators to detect and cope with
      inaccuracies in the haptic guidance. 

PMID- 25850095
TI  - DietCam: Multiview Food Recognition Using a Multikernel SVM.
AB  - Food recognition is a key component in evaluation of everyday food intakes, and
      its challenge is due to intraclass variation. In this paper, we present an
      automatic food classification method, DietCam, which specifically addresses the
      variation of food appearances. DietCam consists of two major components,
      ingredient detection and food classification. Food ingredients are detected
      through a combination of a deformable part-based model and a texture verification
      model. From the detected ingredients, food categories are classified using a
      multiview multikernel SVM. In the experiment, DietCam presents reliability and
      outperformance in recognition of food with complex ingredients on a database
      including 15,262 food images of 55 food types.

PMID- 25850096
TI  - CASDES: A Computer-Aided System to Support Dry Eye Diagnosis Based on Tear Film
      Maps.
AB  - Dry eye syndrome is recognized as a growing health problem, and one of the most
      frequent reasons for seeking eye care. Its etiology and management challenge
      clinicians and researchers alike, and several clinical tests can be used to
      diagnose it. One of the most frequently used tests is the evaluation of the
      interference patterns of the tear film lipid layer. Based on this clinical test,
      this paper presents CASDES, a computer-aided system to support the diagnosis of
      dry eye syndrome. Furthermore, CASDES is also useful to support the diagnosis of
      other eye diseases, such as meibomian gland dysfunction, since it provides a tear
      film map with highly useful information for eye practitioners. Experiments
      demonstrate the robustness of this novel tool, which outperforms the previous
      attempts to create tear film maps and provides reliable results in comparison
      with the clinicians' annotations. Note that the processing time is noticeably
      reduced with the proposed method, which will help to promote its clinical use in
      the diagnosis and treatment of dry eye.

PMID- 25850097
TI  - Validation of an Accelerometer to Quantify a Comprehensive Battery of Gait
      Characteristics in Healthy Older Adults and Parkinson's Disease: Toward Clinical
      and at Home Use.
AB  - Measurement of gait is becoming important as a tool to identify disease and
      disease progression, yet to date its application is limited largely to specialist
      centers. Wearable devices enables gait to be measured in naturalistic
      environments, however questions remain regarding validity. Previous research
      suggests that when compared with a laboratory reference, measurement accuracy is
      acceptable for mean but not variability or asymmetry gait characteristics. Some
      fundamental reasons for this have been presented, (e.g., synchronization,
      different sampling frequencies) but to date this has not been systematically
      examined. The aims of this study were to: 1) quantify a comprehensive range of
      gait characteristics measured using a single triaxial accelerometer-based
      monitor; 2) examine outcomes and monitor performance in measuring gait in older
      adults and those with Parkinson's disease (PD); and 3) carry out a detailed
      comparison with those derived from an instrumented walkway to account for any
      discrepancies. Fourteen gait characteristics were quantified in 30 people with
      incident PD and 30 healthy age-matched controls. Of the 14 gait characteristics
      compared, agreement between instruments was excellent for four (ICCs 0.913
      0.983); moderate for four (ICCs 0.508-0.766); and poor for six characteristics
      (ICCs 0.637-0.370). Further analysis revealed that differences reflect an
      increased sensitivity of accelerometry to detect motion, rather than measurement
      error. This is most likely because accelerometry measures gait as a continuous
      activity rather than discrete footfall events, per instrumented tools. The
      increased sensitivity shown for these characteristics will be of particular
      interest to researchers keen to interpret "real-world" gait data. In conclusion,
      use of a body-worn monitor is recommended for the measurement of gait but is
      likely to yield more sensitive data for asymmetry and variability features.

PMID- 25850098
TI  - Adaptive Neural Network Control of an Uncertain Robot With Full-State
      Constraints.
AB  - This paper studies the tracking control problem for an uncertain n -link robot
      with full-state constraints. The rigid robotic manipulator is described as a
      multiinput and multioutput system. Adaptive neural network (NN) control for the
      robotic system with full-state constraints is designed. In the control design,
      the adaptive NNs are adopted to handle system uncertainties and disturbances. The
      Moore-Penrose inverse term is employed in order to prevent the violation of the
      full-state constraints. A barrier Lyapunov function is used to guarantee the
      uniform ultimate boundedness of the closed-loop system. The control performance
      of the closed-loop system is guaranteed by appropriately choosing the design
      parameters. Simulation studies are performed to illustrate the effectiveness of
      the proposed control. 

PMID- 25850099
TI  - Filtering of Interval Type-2 Fuzzy Systems With Intermittent Measurements.
AB  - In this paper, the problem of fuzzy filter design is investigated for a class of
      nonlinear networked systems on the basis of the interval type-2 (IT2) fuzzy set
      theory. In the design process, two vital factors, intermittent data packet
      dropouts and quantization, are taken into consideration. The parameter
      uncertainties are handled effectively by the IT2 membership functions determined
      by lower and upper membership functions and relative weighting functions. A novel
      fuzzy filter is designed to guarantee the error system to be stochastically
      stable with Hinfinity performance. Moreover, the filter does not need to share
      the same membership functions and number of fuzzy rules as those of the plant.
      Finally, illustrative examples are provided to illustrate the effectiveness of
      the method proposed in this paper. 

PMID- 25850100
TI  - On Configuration Trajectory Formation in Spatiotemporal Profile for Reproducing
      Human Hand Reaching Movement.
AB  - Most functional reaching activities in daily living generally require a hand to
      reach the functional position in appropriate orientation with invariant
      spatiotemporal profile. Effectively reproducing such spatiotemporal feature of
      hand configuration trajectory in real time is essential to understand the human
      motor control and plan human-like motion on anthropomorphic robotic arm. However,
      there are no novel computational models in literature toward reproducing hand
      configuration-to-configuration movement in spatiotemporal profile. In response to
      the problem, this paper presents a computational framework for hand configuration
      trajectory formation based on hierarchical principle of human motor control. The
      composite potential field is constructed on special Euclidean Group to induce
      time-varying configuration toward target. The dynamic behavior of hand is
      described by a second-order kinematic model to produce the external
      representation of high-level motor control. The multivariate regression relation
      between intrinsic and extrinsic coordinates of arm, is statistically analyzed for
      determining the arm orientation in real time, which produces the external
      representation of low-level motor control. The proposed method is demonstrated in
      an anthropomorphic arm by performing several highly curved self-reaching
      movements. The generated configuration trajectories are compared with actual
      human movement in spatiotemporal profile to validate the proposed method. 

PMID- 25850101
TI  - Relative Attribute SVM+ Learning for Age Estimation.
AB  - When estimating age, human experts can provide privileged information that
      encodes the facial attributes of aging, such as smoothness, face shape, face
      acne, wrinkles, and bags under-eyes. In automatic age estimation, privileged
      information is unavailable to test images. To overcome this problem, we
      hypothesize that asymmetric information can be explored and exploited to improve
      the generalizability of the trained model. Using the learning using privileged
      information (LUPI) framework, we tested this hypothesis by carefully defining
      relative attributes for support vector machine (SVM+) to improve the performance
      of age estimation. We term this specific setting as relative attribute SVM+
      (raSVM+), in which the privileged information enables separation of outliers from
      inliers at the training stage and effectively manipulates slack variables and age
      determination errors during model training, and thus guides the trained predictor
      toward a generalizable solution. Experimentally, the superiority of raSVM+ was
      confirmed by comparing it with state-of-the-art algorithms on the face and
      gesture recognition research network (FG-NET) and craniofacial longitudinal
      morphological face aging databases. raSVM+ is a promising development that
      improves age estimation, with the mean absolute error reaching 4.07 on FG-NET. 

PMID- 25850102
TI  - Life Strain, Social Control, Social Learning, and Delinquency: The Effects of
      Gender, Age, and Family SES Among Chinese Adolescents.
AB  - Very few studies have examined the pathways to delinquency and causal factors for
      demographic subgroups of adolescents in a different culture. This article
      explores the effects of gender, age, and family socioeconomic status (SES) in an
      integrated model of strain, social control, social learning, and delinquency
      among a sample of Chinese adolescents. ANOVA is used to check for significant
      differences between categories of demographic groups on the variables in the
      integrated model, and the differential effects of causal factors in the
      theoretical path models are examined. Further tests of interaction effects are
      conducted to compare path coefficients between "high-risk" youths (i.e., male,
      mid-teen, and low family SES adolescents) and other subgroups. The findings
      identified similar pathways to delinquency across subgroups and clarified the
      salience of causal factors for male, mid-teen, and low SES adolescents in a
      different cultural context. 

PMID- 25850103
TI  - A Review of Questionnaire Measures for Assessing the Social Climate in Prisons
      and Forensic Psychiatric Hospitals.
AB  - Significant time and resources are devoted to the monitoring of social climate in
      secure settings. However, if these efforts are to help (rather than hinder)
      attempts to improve the functioning of such units, the monitoring of social
      climate must be based on sound psychometric methods. The aim of this review was
      to determine what questionnaires exist to measure the social climate in secure
      settings and what evidence exists regarding their psychometric properties. Twelve
      questionnaire-based measures of social climate were identified. The Essen Climate
      Evaluation Schema has received the most consistent empirical support, but this
      questionnaire does not provide as much of an in-depth, detailed insight into
      social climate as that provided by other social climate questionnaires. Although
      more extensive measures of climate exist, they have not yet received sufficient
      validation to justify their routine use in practice. Nevertheless, there is
      growing evidence that some questionnaire-based measures can provide a reliable
      and valid assessment of the social climate in secure settings, which has
      important clinical and theoretical implications. 

PMID- 25850104
TI  - Using Satellite-Based Spatiotemporal Resolved Air Temperature Exposure to Study
      the Association between Ambient Air Temperature and Birth Outcomes in
      Massachusetts.
AB  - BACKGROUND: Studies looking at air temperature (Ta) and birth outcomes are rare.
      OBJECTIVES: We investigated the association between birth outcomes and daily Ta
      during various prenatal exposure periods in Massachusetts (USA) using both
      traditional Ta stations and modeled addresses. METHODS: We evaluated birth
      outcomes and average daily Ta during various prenatal exposure periods in
      Massachusetts (USA) using both traditional Ta stations and modeled address Ta. We
      used linear and logistic mixed models and accelerated failure time models to
      estimate associations between Ta and the following outcomes among live births >
      22 weeks: term birth weight (>= 37 weeks), low birth weight (LBW; < 2,500 g at
      term), gestational age, and preterm delivery (PT; < 37 weeks). Models were
      adjusted for individual-level socioeconomic status, traffic density, particulate
      matter <= 2.5 MUm (PM2.5), random intercept for census tract, and mother's
      health. RESULTS: Predicted Ta during multiple time windows before birth was
      negatively associated with birth weight: Average birth weight was 16.7 g lower
      (95% CI: -29.7, -3.7) in association with an interquartile range increase (8.4 
      degrees C) in Ta during the last trimester. Ta over the entire pregnancy was
      positively associated with PT [odds ratio (OR) = 1.02; 95% CI: 1.00, 1.05] and
      LBW (OR = 1.04; 95% CI: 0.96, 1.13). CONCLUSIONS: Ta during pregnancy was
      associated with lower birth weight and shorter gestational age in our study
      population.

PMID- 25850105
TI  - The effect of geography and citizen behavior on motor vehicle deaths in the
      United States.
AB  - Death due to motor vehicle collisions (MVCs) remains a leading cause of death in
      the US and alcohol plays a prominent role in a large proportion of these
      fatalities nationwide. Rates for these incidents vary widely among states and
      over time. Here, we explore the extent to which driving volume, alcohol
      consumption, legislation, political ideology, and geographical factors influence
      MVC deaths across states and time. We specify structural equation models for
      extracting associations between the factors and outcomes for MVC deaths and
      compute correlation functions of states' relative geographic and political
      positions to elucidate the relative contribution of these factors. We find
      evidence that state-level variation in MVC deaths is associated with time-varying
      driving volume, alcohol consumption, and legislation. These relationships are
      modulated by state spatial proximity, whereby neighboring states are found to
      share similar MVC death rates over the thirty-year observation period. These
      results support the hypothesis that neighboring states exhibit similar risk and
      protective characteristics, despite differences in political ideology. 

PMID- 25850106
TI  - Prenatal Phthalate Exposure and Childhood Growth and Blood Pressure: Evidence
      from the Spanish INMA-Sabadell Birth Cohort Study.
AB  - BACKGROUND: Human evidence on the effects of early life phthalate exposure on
      obesity and cardiovascular disease risks, reported by experimental studies, is
      limited to a few cross-sectional studies. OBJECTIVES: We evaluated the
      associations between prenatal phthalate exposure and childhood growth and blood
      pressure in a Spanish birth cohort study. METHODS: We assessed exposure using the
      average of two phthalate metabolite spot-urine concentrations collected from the
      mothers in the first and third pregnancy trimesters (creatinine-adjusted, n =
      391). Study outcomes were the difference in age- and sex-specific z-scores for
      weight between birth and 6 months of age; and repeated age- and sex-specific z
      scores for body mass index (BMI) at 1, 4, and 7 years; waist-to-height ratio at 4
      and 7 years; and age- and height-specific z-scores for systolic and diastolic
      blood pressure at 4 and 7 years. RESULTS: The sum of five high-molecular-weight
      phthalate metabolites (SigmaHMWPm) was associated with lower weight z-score
      difference between birth and 6 months (beta per doubling of exposure = -0.41; 95%
      CI: -0.75, -0.06) and BMI z-scores at later ages in boys (beta = -0.28; 95% CI: 
      0.60, 0.03) and with higher weight z-score difference (beta = 0.24; 95% CI: 
      0.16, 0.65) and BMI z-scores in girls (beta = 0.30; 95% CI: -0.04, 0.64) (p for
      sex interaction = 0.01 and 0.05, respectively). The sum of three low-molecular
      weight phthalates (SigmaLMWPm) was not significantly associated with any of the
      growth outcomes. SigmaHMWPm and SigmaLMWPm were associated with lower systolic
      blood pressure z-scores in girls but not in boys. CONCLUSIONS: This study
      suggests that prenatal phthalate exposure may be associated with postnatal growth
      and blood pressure in a sex-specific manner. Inconsistencies with previous cross
      sectional findings highlight the necessity for evaluating phthalate health
      effects in prospective studies.

PMID- 25850108
TI  - Gold Nanorod-pNIPAM Hybrids with Reversible Plasmon Coupling: Synthesis,
      Modeling, and SERS Properties.
AB  - The thermoresponsive optical properties of Au nanorod-doped poly(N
      isopropylacrylamide) (Au NR-pNIPAM) microgels with different Au NR payloads and
      aspect ratios are presented. Since the volume phase transition of pure pNIPAM
      microgels is reversible, the optical response reversibility of Au NR-pNIPAM
      hybrids is systematically analyzed. Besides, extinction cross-section and near
      field enhancement simulations for Au NR-microgel hybrids are performed using a
      new numerical method based on the surface integral equation method of moments
      formulation (M3 solver). Additionally, the Au NR-microgel hybrid systems are
      expected to serve as excellent broadband surface-enhanced Raman scattering (SERS)
      substrates due to the temperature-controlled formation of hot spots and the
      tunable optical properties. The optical enhancing properties related to SERS are
      tested with three laser lines, evidencing excitation wavelength-dependent
      efficiency that can be easily controlled by either the aspect ratio
      (length/width) of the assembled Au NR or by the Au NR payload per microgel.
      Finally, the SERS efficiency of the prepared Au NR-pNIPAM hybrids is found to be
      stable for months.

PMID- 25850107
TI  - Transdermal Uptake of Diethyl Phthalate and Di(n-butyl) Phthalate Directly from
      Air: Experimental Verification.
AB  - BACKGROUND: Fundamental considerations indicate that, for certain phthalate
      esters, dermal absorption from air is an uptake pathway that is comparable to or
      greater than inhalation. Yet this pathway has not been experimentally evaluated
      and has been largely overlooked when assessing uptake of phthalate esters.
      OBJECTIVES: This study investigated transdermal uptake, directly from air, of
      diethyl phthalate (DEP) and di(n-butyl) phthalate (DnBP) in humans. METHODS: In a
      series of experiments, six human participants were exposed for 6 hr in a chamber
      containing deliberately elevated air concentrations of DEP and DnBP. The
      participants either wore a hood and breathed air with phthalate concentrations
      substantially below those in the chamber or did not wear a hood and breathed
      chamber air. All urinations were collected from initiation of exposure until 54
      hr later. Metabolites of DEP and DnBP were measured in these samples and
      extrapolated to parent phthalate intakes, corrected for background and hood air
      exposures. RESULTS: For DEP, the median dermal uptake directly from air was 4.0
      MUg/(MUg/m(3) in air) compared with an inhalation intake of 3.8 MUg/(MUg/m(3) in
      air). For DnBP, the median dermal uptake from air was 3.1 MUg/(MUg/m(3) in air)
      compared with an inhalation intake of 3.9 MUg/(MUg/m(3) in air). CONCLUSIONS:
      This study shows that dermal uptake directly from air can be a meaningful
      exposure pathway for DEP and DnBP. For other semivolatile organic compounds
      (SVOCs) whose molecular weight and lipid/air partition coefficient are in the
      appropriate range, direct absorption from air is also anticipated to be
      significant.

PMID- 25850109
TI  - An estimation of finger-tapping rates and load capacities and the effects of
      various factors.
AB  - OBJECTIVE: The aim of this study was to estimate the finger-tapping rates and
      finger load capacities of eight fingers (excluding thumbs) for a healthy adult
      population and investigate the effects of various factors on tapping rate.
      BACKGROUND: Finger-tapping rate, the total number of finger taps per unit of
      time, can be used as a design parameter of various products and also as a
      psychomotor test for evaluating patients with neurologic problems. METHOD: A 1
      min tapping task was performed by 148 participants with maximum volitional tempo
      for each of eight fingers. For each of the tapping tasks, the participant with
      the corresponding finger tapped the associated key in the standard position on
      the home row of a conventional keyboard for touch typing. RESULTS: The index and
      middle fingers were the fastest fingers for both hands, and little fingers the
      slowest. All dominant-hand fingers, except little finger, had higher tapping
      rates than the fastest finger of the nondominant hand. Tapping rate decreased
      with age and smokers tapped faster than nonsmokers. Tapping duration and exercise
      had also significant effect on tapping rate. CONCLUSION: Normative data of
      tapping rates and load capacities of eight fingers were estimated for the adult
      population. In designs of psychomotor tests that require the use of tapping rate
      or finger load capacity data, the effects of finger, age, smoking, and tapping
      duration need to be taken into account. APPLICATION: The findings can be used for
      ergonomic designs requiring finger-tapping capacity and also as a reference in
      psychomotor tests.

PMID- 25850110
TI  - Clutter in electronic medical records: examining its performance and attentional
      costs using eye tracking.
AB  - OBJECTIVE: The objective was to use eye tracking to trace the underlying changes
      in attention allocation associated with the performance effects of clutter,
      stress, and task difficulty in visual search and noticing tasks. BACKGROUND:
      Clutter can degrade performance in complex domains, yet more needs to be known
      about the associated changes in attention allocation, particularly in the
      presence of stress and for different tasks. Frequently used and relatively simple
      eye tracking metrics do not effectively capture the various effects of clutter,
      which is critical for comprehensively analyzing clutter and developing targeted,
      real-time countermeasures. METHOD: Electronic medical records (EMRs) were chosen
      as the application domain for this research. Clutter, stress, and task difficulty
      were manipulated, and physicians' performance on search and noticing tasks was
      recorded. Several eye tracking metrics were used to trace attention allocation
      throughout those tasks, and subjective data were gathered via a debriefing
      questionnaire. RESULTS: Clutter degraded performance in terms of response time
      and noticing accuracy. These decrements were largely accentuated by high stress
      and task difficulty. Eye tracking revealed the underlying attentional mechanisms,
      and several display-independent metrics were shown to be significant indicators
      of the effects of clutter. CONCLUSION: Eye tracking provides a promising means to
      understand in detail (offline) and prevent (in real time) major performance
      breakdowns due to clutter. APPLICATION: Display designers need to be aware of the
      risks of clutter in EMRs and other complex displays and can use the identified
      eye tracking metrics to evaluate and/or adjust their display.

PMID- 25850111
TI  - Using Modeling and Simulation to Predict Operator Performance and Automation
      Induced Complacency With Robotic Automation: A Case Study and Empirical
      Validation.
AB  - OBJECTIVE: The aim of this study was to develop and validate a computational
      model of the automation complacency effect, as operators work on a robotic arm
      task, supported by three different degrees of automation. BACKGROUND: Some
      computational models of complacency in human-automation interaction exist, but
      those are formed and validated within the context of fairly simplified monitoring
      failures. This research extends model validation to a much more complex task, so
      that system designers can establish, without need for human-in-the-loop (HITL)
      experimentation, merits and shortcomings of different automation degrees. METHOD:
      We developed a realistic simulation of a space-based robotic arm task that could
      be carried out with three different levels of trajectory visualization and
      execution automation support. Using this simulation, we performed HITL testing.
      Complacency was induced via several trials of correctly performing automation and
      then was assessed on trials when automation failed. Following a cognitive task
      analysis of the robotic arm operation, we developed a multicomponent model of the
      robotic operator and his or her reliance on automation, based in part on visual
      scanning. RESULTS: The comparison of model predictions with empirical results
      revealed that the model accurately predicted routine performance and predicted
      the responses to these failures after complacency developed. However, the
      scanning models do not account for the entire attention allocation effects of
      complacency. APPLICATIONS: Complacency modeling can provide a useful tool for
      predicting the effects of different types of imperfect automation. The results
      from this research suggest that focus should be given to supporting situation
      awareness in automation development.

PMID- 25850112
TI  - Visual Performance With Small Concave and Convex Displays.
AB  - OBJECTIVE: In this study, we aim to investigate how users' visual performance
      with a small flexible display changes based on the direction (i.e., convex,
      concave) and the magnitude (i.e., low, high) of the display curvature.
      BACKGROUND: Despite the wide interest in flexible display materials and
      deformable displays, the potential effects of nonplanar display surfaces on human
      perception and performance have received little attention. This study is the
      first to demonstrate how curving affects visual performance with an actual
      flexible display (4.5-in. active-matrix organic light-emitting diode). METHOD: In
      a series of three experiments, we compared the performance with a planar display
      to the performance with concave and convex display surfaces with low and high
      curvature magnitudes. Two visual search tasks were employed that required the
      subject to detect target letters based on their contrast (Experiments 1 and 2)
      and identity (Experiment 3). Performance was measured as the sensitivity of
      target detection (d') and threshold time of the search, respectively. RESULTS:
      There were similar sensitivities for targets across the curvature variants, but
      the high-magnitude curvatures resulted in prolonged search times, especially for
      the convex form. In both of the tasks, performance was dependent on the display
      location, which was defined as the target's distance from the display center.
      CONCLUSION: High curvature magnitudes should be avoided, even in small displays,
      because large local changes in visual stimuli decrease processing speed outside
      the central display. APPLICATION: The findings have implications for the
      development of technologies, applications, and user interfaces for flexible
      displays and the design of visual display devices.

PMID- 25850114
TI  - The Impact of Sleep Disruption on Complex Cognitive Tasks: A Meta-Analysis.
AB  - OBJECTIVE: We aimed to build upon the state of knowledge about the impacts of
      sleep disruption into the domain of complex cognitive task performance for three
      types of sleep disruption: total sleep deprivation, sleep restriction, and
      circadian cycle. BACKGROUND: Sleep disruption affects human performance by
      increasing the likelihood of errors or the time it takes to complete tasks, such
      as the Psychomotor Vigilance Task. It is not clear whether complex tasks are
      affected in the same way. Understanding the impact of sleep disruption on complex
      cognitive tasks is important for, and in some instances more relevant to,
      professional workers confronted with unexpected, catastrophic failures following
      a period of disrupted sleep. METHOD: Meta-analytic review methods were applied to
      each of the three different areas of sleep disruption research. RESULTS: Complex
      cognitive task performance declines over consecutive hours of continuous
      wakefulness as well as consecutive days of restricted sleep, is worse for
      severely restricted sleep (4 or fewer hours in bed), is worse during the
      circadian nadir than apex, and appears less degraded than simple task
      performance. CONCLUSION: The reviews suggest that complex cognitive task
      performance may not be impacted by disrupted sleep as severely as simple
      cognitive task performance. APPLICATION: Findings apply to predicting effects of
      sleep disruption on workers in safety-critical environments, such as health care,
      aviation, the military, process control, and in particular, safety-critical
      environments involving shiftwork or long-duration missions.

PMID- 25850113
TI  - Asynchronous Brainstorming in an Industrial Setting: Exploratory Studies.
AB  - OBJECTIVE: The goal of this study was to examine the effectiveness of
      brainwriting in an industrial setting. BACKGROUND: Research has demonstrated that
      group interaction can inhibit idea generation. Written exchanges of ideas in
      groups have been found to be an effective way to increase idea generation. To our
      knowledge, no study has examined the potential of brainwriting for group idea
      generation in work settings or the impact of different sequences of group and
      individual idea generation. METHOD: Participants in a high-technology company
      participated in two brainwriting studies. In one study, participants generated
      ideas either first alone and then in a group or in the reverse order. In a second
      study, participants either generated as a group during the entire session or
      alternated individual ideation with a periodic review of the group's ideas.
      RESULTS: In the first study, participants who generated ideas first as a group
      and then as individuals performed best. In the first session, group writing also
      tended to lead to more ideas than did individual writing. In the second study,
      participants with periodic reviews performed best. CONCLUSION: The results
      suggest that alternation in individual and group brainwriting can enhance the
      number of ideas generated. The group-to-alone sequence is also beneficial since
      it allows group members to build on shared ideas. APPLICATION: This research
      indicates that collaborative idea sessions can be beneficial in work sessions if
      the brainwriting paradigm is used with an appropriate alternation of group
      ideation or review sessions with individual idea generation sessions.

PMID- 25850115
TI  - Effects of Stereoscopic Depth on Vigilance Performance and Cerebral Hemodynamics.
AB  - OBJECTIVE: We tested the possibility that monitoring a display wherein critical
      signals for detection were defined by a stereoscopic three-dimensional (3-D)
      image might be more resistant to the vigilance decrement, and to temporal
      declines in cerebral blood flow velocity (CBFV), than monitoring a display
      featuring a customary two-dimensional (2-D) image. BACKGROUND: Hancock has
      asserted that vigilance studies typically employ stimuli for detection that do
      not exemplify those that occur in the natural world. As a result, human
      performance is suboptimal. From this perspective, tasks that better approximate
      perception in natural environments should enhance performance efficiency. To test
      that possibility, we made use of stereopsis, an important means by which
      observers interact with their everyday surroundings. METHOD: Observers monitored
      a circular display in which a vertical line was embedded. Critical signals for
      detection in a 2-D condition were instances in which the line was rotated
      clockwise from vertical. In a 3-D condition, critical signals were cases in which
      the line appeared to move outward toward the observer. RESULTS: The overall level
      of signal detection and the stability of detection over time were greater when
      observers monitored for 3-D changes in target depth compared to 2-D changes in
      target orientation. However, the 3-D display did not retard the temporal decline
      in CBFV. CONCLUSION: These results provide the initial demonstration that 3-D
      displays can enhance performance in vigilance tasks. APPLICATION: The use of 3-D
      displays may be productive in augmenting system reliability when operator
      vigilance is vital.

PMID- 25850116
TI  - Smartphone Text Input Method Performance, Usability, and Preference With Younger
      and Older Adults.
AB  - OBJECTIVE: User performance, perceived usability, and preference for five
      smartphone text input methods were compared with younger and older novice adults.
      BACKGROUND: Smartphones are used for a variety of functions other than phone
      calls, including text messaging, e-mail, and web browsing. Research comparing
      performance with methods of text input on smartphones reveals a high degree of
      variability in reported measures, procedures, and results. This study reports on
      a direct comparison of five of the most common input methods among a population
      of younger and older adults, who had no experience with any of the methods.
      METHOD: Fifty adults (25 younger, 18-35 years; 25 older, 60-84 years) completed a
      text entry task using five text input methods (physical Qwerty, onscreen Qwerty,
      tracing, handwriting, and voice). Entry and error rates, perceived usability, and
      preference were recorded. RESULTS: Both age groups input text equally fast using
      voice input, but older adults were slower than younger adults using all other
      methods. Both age groups had low error rates when using physical Qwerty and
      voice, but older adults committed more errors with the other three methods. Both
      younger and older adults preferred voice and physical Qwerty input to the
      remaining methods. Handwriting consistently performed the worst and was rated
      lowest by both groups. CONCLUSION: Voice and physical Qwerty input methods proved
      to be the most effective for both younger and older adults, and handwriting input
      was the least effective overall. APPLICATION: These findings have implications to
      the design of future smartphone text input methods and devices, particularly for
      older adults.

PMID- 25850117
TI  - Comparison of Two Watch Schedules for Personnel at the White House Military
      Office President's Emergency Operations Center.
AB  - OBJECTIVE: The aim of this study was to assess effectiveness of an alternative,
      24-hr-on/72-hr-off watchstanding schedule on sleep and morale of personnel
      assigned to the President's Emergency Operations Center (PEOC). BACKGROUND: As
      part of the White House Military Office, PEOC personnel historically worked a 12
      hr "Panama" watch schedule. Personnel reported experiencing chronic insufficient
      and disrupted sleep patterns and sought advice for improving their watchstanding
      schedule. METHOD: Participants (N = 14 active-duty military members, ages 29 to
      42 years) completed the Profile of Mood State (POMS) three times: before, during,
      and after switching to the alternative schedule with 5-hr sleep periods built
      into their workday. Participants completed a poststudy questionnaire to assess
      individual schedule preferences. Sleep was measured actigraphically, supplemented
      by activity logs. RESULTS: As indicated by POMS scores, mood improved
      significantly on the new schedule. Although average total sleep amount did not
      change substantively, the timing of sleep was more consistent on the new
      schedule, resulting in better sleep hygiene. PEOC personnel overwhelmingly
      preferred the new schedule, reporting not only that they felt more rested but
      that the new schedule was more conducive to the demands of family life.
      CONCLUSIONS: Demands of family life and time spent commuting were found to be
      critical factors for acceptance of the alternative schedule. This new schedule
      will be most effective if personnel adhere to the scheduled rest periods assigned
      during their 24-hr duty. APPLICATION: A successful schedule should avoid
      conflicts between social life and operational demands. Results may lead to
      changes in the work schedules of other departments with similar 24/7
      responsibilities.

PMID- 25850118
TI  - Usability and Safety in Electronic Medical Records Interface Design: A Review of
      Recent Literature and Guideline Formulation.
AB  - OBJECTIVE: The objectives of this study were to (a) review electronic medical
      record (EMR) and related electronic health record (EHR) interface usability
      issues, (b) review how EMRs have been evaluated with safety analysis techniques
      along with any hazard recognition, and (c) formulate design guidelines and a
      concept for enhanced EMR interfaces with a focus on diagnosis and documentation
      processes. BACKGROUND: A major impact of information technology in health care
      has been the introduction of EMRs. Although numerous studies indicate use of EMRs
      to increase health care quality, there remain concerns with usability issues and
      safety. METHOD: A literature search was conducted using Compendex, PubMed,
      CINAHL, and Web of Science databases to find EMR research published since 2000.
      Inclusion criteria included relevant English-language papers with subsets of
      keywords and any studies (manually) identified with a focus on EMR usability.
      RESULTS: Fifty studies met the inclusion criteria. Results revealed EMR and EHR
      usability problems to include violations of natural dialog, control consistency,
      effective use of language, effective information presentation, and customization
      principles as well as a lack of error prevention, minimization of cognitive load,
      and feedback. Studies focusing on EMR system safety made no objective assessments
      and applied only inductive reasoning methods for hazard recognition. CONCLUSION:
      On the basis of the identified usability problems and structure of safety
      analysis techniques, we provide EMR design guidelines and a design concept
      focused on the diagnosis process and documentation. APPLICATION: The design
      guidelines and new interface concept can be used for prototyping and testing
      enhanced EMRs.

PMID- 25850119
TI  - America's medical school: 5,000 graduates since the "first class".
AB  - In 1980, the Uniformed Services University of the Health Sciences (USU) graduated
      its first class of medical students. As a national university intended to produce
      "career-committed" military officers and future leaders of the Military Health
      System, USU functions as the service academy for military medicine and public
      health. More than 40 years after the school's charter and 5,000 graduates since
      the first class, we describe the original purpose of USU and provide an update on
      its achievements. In particular, we address the question of the "staying power"
      of the University's alumni-the degree to which graduation from the nation's
      military medical school is associated with long years of devoted service to
      military medicine. At a time when the MHS is confronting the challenge of
      extended deployments, rising health care costs, and a growing array of threats to
      our nation's health, we suggest that America needs USU now more than ever. 

PMID- 25850120
TI  - Does the MCAT predict medical school and PGY-1 performance?
AB  - BACKGROUND: The Medical College Admissions Test (MCAT) is a high-stakes test
      required for entry to most U. S. medical schools; admissions committees use this
      test to predict future accomplishment. Although there is evidence that the MCAT
      predicts success on multiple choice-based assessments, there is little
      information on whether the MCAT predicts clinical-based assessments of
      undergraduate and graduate medical education performance. This study looked at
      associations between the MCAT and medical school grade point average (GPA),
      Medical Licensing Examination (USMLE) scores, observed patient care encounters,
      and residency performance assessments. METHODS: This study used data collected as
      part of the Long-Term Career Outcome Study to determine associations between MCAT
      scores, USMLE Step 1, Step 2 clinical knowledge and clinical skill, and Step 3
      scores, Objective Structured Clinical Examination performance, medical school
      GPA, and PGY-1 program director (PD) assessment of physician performance for
      students graduating 2010 and 2011. RESULTS: MCAT data were available for all
      students, and the PGY PD evaluation response rate was 86.2% (N = 340). All
      permutations of MCAT scores (first, last, highest, average) were weakly
      associated with GPA, Step 2 clinical knowledge scores, and Step 3 scores. MCAT
      scores were weakly to moderately associated with Step 1 scores. MCAT scores were
      not significantly associated with Step 2 clinical skills Integrated Clinical
      Encounter and Communication and Interpersonal Skills subscores, Objective
      Structured Clinical Examination performance or PGY-1 PD evaluations. DISCUSSION:
      MCAT scores were weakly to moderately associated with assessments that rely on
      multiple choice testing. The association is somewhat stronger for assessments
      occurring earlier in medical school, such as USMLE Step 1. The MCAT was not able
      to predict assessments relying on direct clinical observation, nor was it able to
      predict PD assessment of PGY-1 performance.

PMID- 25850121
TI  - Predicting medical school and internship success: does the quality of the
      research and clinical experience matter?
AB  - OBJECTIVES: This article explores specific aspects of self-reported clinical and
      research experience and their relationship to performance in medical training.
      METHODS: This is a retrospective cohort study conducted at the Uniformed Services
      University. The American Medical College Application Service application was used
      to discern students' self-reported clinical and research experience. Two authors
      applied a classification scheme for clinical and research experience to the self
      reported experiences. Study outcomes included medical school grade point average
      (GPA), U.S. Medical Licensing Examination (USMLE) scores, and intern expertise
      and professionalism scores. A linear regression analysis was conducted for each
      outcome while controlling for prematriculation GPA. RESULTS: Data were retrieved
      on 1,020 matriculants. There were several statistically significant but small
      differences across outcomes when comparing the various categories of clinical
      experience with no clinical experience. The technician-level experience group had
      a decrease of 0.1 in cumulative GPA in comparison to students without self
      reported clinical experience (p = 0.004). This group also performed 5 points
      lower on the USMLE Step 2 than students who did not report clinical experience (p
      = 0.013). The various levels of self-reported research experience were unrelated
      to success in medical school and graduate medical education. DISCUSSION: These
      findings indicate that self-reported technician-level clinical experience is
      related to a small reduction in typically reported outcomes in medical school.

PMID- 25850122
TI  - Are commonly used premedical school or medical school measures associated with
      board certification?
AB  - PURPOSE: To determine if there is an association between several commonly
      obtained premedical school and medical school measures and board certification
      performance. We specifically included measures from our institution for which we
      have predictive validity evidence into the internship year. We hypothesized that
      board certification would be most likely to be associated with clinical measures
      of performance during medical school, and with scores on standardized tests,
      whether before or during medical school. METHODS: Achieving board certification
      in an American Board of Medical Specialties specialty was used as our outcome
      measure for a 7-year cohort of graduates (1995-2002). Age at matriculation,
      Medical College Admissions Test (MCAT) score, undergraduate college grade point
      average (GPA), undergraduate college science GPA, Uniformed Services University
      (USU) cumulative GPA, USU preclerkship GPA, USU clerkship year GPA, departmental
      competency committee evaluation, Internal Medicine (IM) clerkship clinical
      performance rating (points), IM total clerkship points, history of Student
      Promotion Committee review, and United States Medical Licensing Examination
      (USMLE) Step 1 score and USMLE Step 2 clinical knowledge score were associated
      with this outcome. RESULTS: Ninety-three of 1,155 graduates were not certified,
      resulting in an average rate of board certification of 91.9% for the study
      cohort. Significant small correlations were found between board certification and
      IM clerkship points (r = 0.117), IM clerkship grade (r = 0.108), clerkship year
      GPA (r = 0.078), undergraduate college science GPA (r = 0.072), preclerkship GPA
      and medical school GPA (r = 0.068 for both), USMLE Step 1 (r = 0.066),
      undergraduate college total GPA (r = 0.062), and age at matriculation (r = 
      0.061). In comparing the two groups (board certified and not board certified
      cohorts), significant differences were seen for all included variables with the
      exception of MCAT and USMLE Step 2 clinical knowledge scores. All the variables
      put together could explain 4.1% of the variance of board certification by
      logistic regression. CONCLUSIONS: This investigation provides some additional
      validity evidence that measures collected for purposes of student evaluation
      before and during medical school are warranted.

PMID- 25850123
TI  - Longitudinal effects of medical students' communication skills on future
      performance.
AB  - BACKGROUND: The Essential Elements of Communication (EEC) were developed from the
      Kalamazoo consensus statement on physician-patient communication. The Uniformed
      Services University of the Health Sciences (USU) has adopted a longitudinal
      curriculum to use the EEC both as a learning tool during standardized patient
      encounters and as an evaluation tool culminating with the end of preclerkship
      objective-structured clinical examinations (OSCE). Medical educators have
      recently emphasized the importance of teaching communication skills, as evidenced
      by the United States Medical Licensing Examination testing both the integrated
      clinical encounter (ICE) and communication and interpersonal skills (CIS) within
      the Step 2 Clinical Skills exam (CS). PURPOSE: To determine the associations
      between students' EEC OSCE performance at the end of the preclerkship period with
      later communication skills assessment and evaluation outcomes in the context of a
      longitudinal curriculum spanning both undergraduate medical education and
      graduate medical education. METHODS: Retrospective data from preclerkship
      (overall OSCE scores and EEC OSCE scores) and clerkship outcomes (internal
      medicine [IM] clinical points and average clerkship National Board of Medical
      Examiners [NBME] scores) were collected from 167 USU medical students from the
      class of 2011 and compared to individual scores on the CIS and ICE components of
      Step 2 CS, as well as to the communication skills component of the program
      directors' evaluation of trainees during their postgraduate year 1 (PGY-1)
      residency. In addition to bivariate Pearson correlation analysis, we conducted
      multiple linear regression analysis to examine the predictive power of the EEC
      score beyond the IM clerkship clinical points and the average NBME Subject Exams
      score on the outcome measures. RESULTS: The EEC score was a significant predictor
      of the CIS score and the PGY-1 communication skills score. Beyond the average
      NBME Subject Exams score and the IM clerkship clinical points, the EEC score
      explained an additional 13% of the variance in the Step 2 CIS score and an
      additional 6% of the variance in the PGY-1 communication skills score. In
      addition, the EEC score was more closely associated with the CIS score than the
      ICE score. CONCLUSION: The use of a standardized approach with a communication
      tool like the EEC can help explain future performance in communication skills
      independent of other education outcomes. In the context of a longitudinal
      curriculum, this information may better inform medical educators on learners'
      communication capabilities and more accurately direct future remediation efforts.

PMID- 25850124
TI  - Assessing task importance and anxiety in medical school: an instrument
      development and initial validation study.
AB  - Recent research in medical education suggests that students' motivational
      beliefs, such as their beliefs about the importance of a task, and their emotions
      are meaningful predictors of learning and performance. The primary purpose of
      this study was to develop a self-report measure of "task importance" and
      "anxiety" in relation to several medical education competencies and to collect
      validity evidence for the new measures. The secondary purpose was to evaluate
      differences in these measures by year of medical school. Exploratory factor
      analysis of scores from 368 medical school students suggested two task importance
      factors and three anxiety factors. The task importance and anxiety subscales were
      weakly related to each other and exhibited consistently negative and positive
      correlations, respectively, with three self-efficacy subscales. The task
      importance subscales were positively related to "metacognition," whereas
      "interpersonal skills anxiety" and "health knowledge anxiety" were positively
      related to "procrastination." All three anxiety factors were positively related
      to "avoidance of help seeking," whereas "interpersonal skills and professionalism
      importance" was negatively related to help avoidance behaviors. Finally,
      comparisons across the 4 years of medical school indicated that some aspects of
      task importance and anxiety varied significantly. Overall, findings from this
      study provide validity evidence for the psychometric quality of these scales,
      which capture task importance and anxiety in medical students. Limitations and
      implications for medical education research are discussed. 

PMID- 25850125
TI  - Preclerkship assessment of clinical skills and clinical reasoning: the
      longitudinal impact on student performance.
AB  - PURPOSE: Many medical schools across the United States are undergoing curriculum
      reform designed, in part, to integrate basic sciences and clinical skills.
      Evidence has suggested that preclerkship courses in clinical skills and clinical
      reasoning are predictive of student performance on the clerkship. We hypothesized
      that a combination of outcome measures from preclerkship clinical skills and
      clinical reasoning courses (Objective Structured Clinical Examination scores,
      preceptor evaluations, National Board of Medical Examiners subject examination
      scores, and small group participation grades) would be correlated to performance
      in internship (program director [PD]evaluation form at end of first postgraduate
      year). METHODS: Outcome measures from preclerkship clinical skills and clinical
      reasoning courses and PD evaluation forms from 514 medical students graduating
      between 2009 and 2011 were analyzed in a multiple linear regression model.
      RESULTS: Preclerkship clinical skills and clinical reasoning outcome measures
      were significant contributors to the linear regression model and were able to
      explain 13.9% of the variance in expertise and 7.6% of the variance in
      professionalism as measured by the PD evaluation form. CONCLUSION: Clinical
      skills and clinical reasoning courses during the preclerkship period explained a
      significant amount of performance at the graduate medical education level. Our
      data suggest that these courses provide valuable information regarding student
      abilities in internship. Early recognition of struggling students may provide an
      opportunity to break a cycle of poor performance that can persist into residency
      training.

PMID- 25850126
TI  - The association of students requiring remediation in the internal medicine
      clerkship with poor performance during internship.
AB  - PURPOSE: To determine whether the Uniformed Services University (USU) system of
      workplace performance assessment for students in the internal medicine clerkship
      at the USU continues to be a sensitive predictor of subsequent poor performance
      during internship, when compared with assessments in other USU third year
      clerkships. METHOD: Utilizing Program Director survey results from 2007 through
      2011 and U.S. Medical Licensing Examination (USMLE) Step 3 examination results as
      the outcomes of interest, we compared performance during internship for students
      who had less than passing performance in the internal medicine clerkship and
      required remediation, against students whose performance in the internal medicine
      clerkship was successful. We further analyzed internship ratings for students who
      received less than passing grades during the same time period on other third year
      clerkships such as general surgery, pediatrics, obstetrics and gynecology, family
      medicine, and psychiatry to evaluate whether poor performance on other individual
      clerkships were associated with future poor performance at the internship level.
      Results for this recent cohort of graduates were compared with previously
      published findings. RESULTS: The overall survey response rate for this 5 year
      cohort was 81% (689/853). Students who received a less than passing grade in the
      internal medicine clerkship and required further remediation were 4.5 times more
      likely to be given poor ratings in the domain of medical expertise and 18.7 times
      more likely to demonstrate poor professionalism during internship. Further,
      students requiring internal medicine remediation were 8.5 times more likely to
      fail USMLE Step 3. No other individual clerkship showed any statistically
      significant associations with performance at the intern level. On the other hand,
      40% of students who successfully remediated and did graduate were not identified
      during internship as having poor performance. CONCLUSIONS: Unsuccessful clinical
      performance which requires remediation in the third year internal medicine
      clerkship at Uniformed Services University of the Health Sciences continues to be
      strongly associated with poor performance at the internship level. No significant
      associations existed between any of the other clerkships and poor performance
      during internship and Step 3 failure. The strength of this association with the
      internal medicine clerkship is most likely because of an increased level of
      sensitivity in detecting poor performance.

PMID- 25850128
TI  - Medical student attitudes toward the medically underserved: the USU perspective.
AB  - This study examined a cohort of students attending the Uniformed Services
      University regarding their attitudes toward medical care in underserved
      populations. Using the previously validated Medical Student Attitudes Toward the
      Underserved (MSATU), repeated measures analysis of variance showed that student
      attitudes toward care in underserved populations was less favorable than limited
      national data at entry and declined over time (Mean MSATU total score Year 1:
      46.2 [SD 10.95]; Year 4: 41.7 [SD 12.3] p < 0.01). Differences in medical school
      debt, exposure to underserved populations, and the definition of "service" in the
      context of active duty military status might explain some of our findings.
      Providing broad service learning opportunities within the curriculum could
      increase student exposure to underserved populations and strengthen the social
      contract between community and institution. 

PMID- 25850127
TI  - The clinical integrative puzzle for teaching and assessing clinical reasoning:
      preliminary feasibility, reliability, and validity evidence.
AB  - BACKGROUND: Expertise in clinical reasoning is essential for high-quality patient
      care. The Clinical Integrative Puzzle (CIP) is a novel assessment method for
      clinical reasoning. The purpose of our study was to further describe the CIP,
      providing feasibility, reliability, and validity evidence to support this tool
      for teaching and evaluating clinical reasoning. METHODS: We conducted a
      prospective, randomized crossover trial assessing the CIP in second-year medical
      students from a single institution. Feasibility was estimated through the time
      taken to complete a CIP during a CIP session and through comments from faculty
      developers. Reliability was addressed through calculating odd-even item
      reliability (split-half procedure) for grid questions within each CIP. Evidence
      for content, concurrent, and predictive validity was also measured. RESULTS: 36
      students participated in the study. Data suggested successful randomization of
      participants and nonparticipants. The CIP was found to have high feasibility,
      acceptable reliability (0.43-0.73 with a mean of 0.60) with a short time for CIP
      completion. Spearman-Brown correction estimated a reliability of 0.75 with
      completing two grids (estimated time of 50 minutes) and 0.82 for three grids
      (estimated time of 75 minutes). Validity evidence was modest; the CIP is
      consistent with clinical reasoning literature and the CIP modestly correlated
      with small group performance (r = 0.3, p < 0.05). CONCLUSIONS: Assessing clinical
      reasoning in medical students is challenging. Our data provide good feasibility
      and reliability evidence for the use of CIPs; validity data was less robust.

PMID- 25850129
TI  - Using concept maps in a modified team-based learning exercise.
AB  - Medical school education has traditionally been driven by single discipline
      teaching and assessment. Newer medical school curricula often implement an organ
      based approach that fosters integration of basic science and clinical
      disciplines. Concept maps are widely used in education. Through diagrammatic
      depiction of a variety of concepts and their specific connections with other
      ideas, concept maps provide a unique perspective into learning and performance
      that can complement other assessment methods commonly used in medical schools. In
      this innovation, we describe using concepts maps as a vehicle for a modified a
      classic Team-Based Learning (TBL) exercise. Modifications to traditional TBL in
      our innovation included replacing an individual assessment using multiple-choice
      questions with concept maps as well as combining the group assessment and
      application exercise whereby teams created concept maps. These modifications were
      made to further assess understanding of content across the Fundamentals module
      (the introductory module of the preclerkship curriculum). While preliminary,
      student performance and feedback from faculty and students support the use of
      concept maps in TBL. Our findings suggest concept maps can provide a unique means
      of determining assessment of learning and generating feedback to students.
      Concept maps can also demonstrate knowledge acquisition, organization of prior
      and new knowledge, and synthesis of that knowledge across disciplines in a unique
      way providing an additional means of assessment in addition to traditional
      multiple-choice questions. 

PMID- 25850130
TI  - Referral for competency committee review for poor performance on the internal
      medicine clerkship is associated with poor performance in internship.
AB  - PURPOSE: To determine how students who are referred to a competency committee for
      concern over performance, and ultimately judged not to require remediation,
      perform during internship. METHODS: Uniformed Services University of the Health
      Sciences' students who graduated between 2007 and 2011 were included in this
      study. We compared the performance during internship of three groups: students
      who were referred to the internal medicine competency committee for review who
      met passing criterion, students who were reviewed by the internal medicine
      competency committee who were determined not to have passed the clerkship and
      were prescribed remediation, and students who were never reviewed by this
      competency committee. Program Director survey results and United States Medical
      Licensing Examination (USMLE) Step 3 examination results were used as the
      outcomes of interest. RESULTS: The overall survey response rate for this 5-year
      cohort was 81% (689/853). 102 students were referred to this competency committee
      for review. 63/102 students were reviewed by this competency committee, given
      passing grades in the internal medicine clerkship, and were not required to do
      additional remediation. 39/102 students were given less than passing grades by
      this competency committee and required to perform additional clinical work in the
      department of medicine to remediate their performance. 751 students were never
      presented to this competency committee. Compared to students who were never
      presented for review, the group of reviewed students who did not require
      remediation was 5.6 times more likely to receive low internship survey ratings in
      the realm of professionalism, 8.6 times more likely to receive low ratings in the
      domain of medical expertise, and had a higher rate of USMLE Step 3 failure (9.4%
      vs. 2.8%). When comparing the reviewed group to students who were reviewed and
      also required remediation, the only significant difference between groups
      regarding professionalism ratings with 50% of the group requiring remediation
      garnering low ratings compared to 18% of the reviewed group. CONCLUSIONS:
      Students who are referred to a committee for review following completion of their
      internal medicine clerkship are more likely to receive poor ratings in internship
      and fail USMLE Step 3 compared to students whose performance in the medicine
      clerkship does not trigger a committee review. These findings provide validity
      evidence for our competency committee review in that the students identified as
      requiring further clinical work had significantly higher rates of poor ratings in
      professionalism than students who were reviewed by the competency committee but
      not required to remediate. Additionally, students reviewed but not required to
      remediate were nonetheless at risk of low internship ratings, suggesting that
      these students might need some intervention prior to graduation.

PMID- 25850131
TI  - Physical fitness and academic performance: a pilot investigation in USU medical
      students.
AB  - This study examined the correlations between physical fitness parameters and
      standard measures of academic performance in a cohort of students at the
      Uniformed Services University. Significant positive correlations were noted
      between the average aerobic fitness score and preclerkship grade point average
      (GPA; r = 0.37, p < 0.05) and cumulative GPA (r = 0.38, p < 0.05). Positive
      correlations were also noted between the average overall fitness score and
      preclerkship GPA (r = 0.34, p < 0.05), medical school cumulative GPA (r = 0.34, p
      < 0.05), and the score on Step 1 of the national board examination (r = -0.33, p
      < 0.05). Physical fitness may serve as one indicator to predict which students
      will succeed in medical school and to identify those who are at risk for poor
      performance and might benefit from a wellness intervention. 

PMID- 25850132
TI  - Novel examination for evaluating medical student clinical reasoning: reliability
      and association with patients seen.
AB  - BACKGROUND: Medical students learn clinical reasoning, in part, through patient
      care. Although the numbers of patients seen is associated with knowledge
      examination scores, studies have not demonstrated an association between patient
      problems and an assessment of clinical reasoning. AIM: To examine the reliability
      of a clinical reasoning examination and investigate whether there was association
      between internal medicine core clerkship students' performance on this
      examination and the number of patients they saw with matching problems during
      their internal medicine clerkship. METHODS: Students on the core internal
      medicine clerkship at the Uniformed Services University students log 11 core
      patient problems based on the Clerkship Directors in Internal Medicine
      curriculum. On a final clerkship examination (Multistep), students watch a
      scripted video encounter between physician and patient actors that assesses three
      sequential steps in clinical reasoning: Step One focuses on history and physical
      examination; Step Two, students write a problem list after viewing additional
      clinical findings; Step Three, students complete a prioritized differential
      diagnosis and treatment plan. Each Multistep examination has three different
      cases. For graduating classes 2010-2012 (n = 497), we matched the number of
      patients seen with the problem most represented by the Multistep cases
      (epigastric pain, generalized edema, monoarticular arthritis, angina, syncope,
      pleuritic chest pain). We report two-way Pearson correlations between the number
      of patients students reported with similar problems and the student's percent
      score on: Step One, Step Two, Step Three, and Overall Test. RESULTS: Multistep
      reliability: Step 1, 0.6 to 0.8; Step 2, 0.41 to 0.65; Step 3, 0.53 to 0.78;
      Overall examination (3 cases): 0.74 to 0.83. For three problems, the number of
      patients seen had small to modest correlations with the Multistep Examination of
      Analytic Ability total score (r = 0.27 for pleuritic pain, p < 0.05, n = 81
      patients; r = 0.14 for epigastric pain, p < 0.05, n = 324 patients; r = 0.19 for
      generalized edema, p < 0.05, n = 118 patients). DISCUSSION or CONCLUSION:
      Although a reliable assessment, student performance on a clinical reasoning
      examination was weakly associated with the numbers of patients seen with similar
      problems. This may be as a result of transfer of knowledge between clinical and
      examination settings, the complexity of clinical reasoning, or the limits of
      reliability with patient logs and the Multistep.

PMID- 25850133
TI  - A curricular addition using art to enhance reflection on professional values.
AB  - BACKGROUND: Art and humanities can enhance undergraduate medical education
      curricular objectives. Most commonly, art is used to help students learn
      observational skills, such as medical interviewing and physical diagnosis.
      Educators concurrently struggle to find ways to meaningfully teach professional
      values within crowded curricula. AIM: This curriculum aimed to combine art and
      reflection to actively convey tenets of medical professionalism. SETTING:
      Internal medicine clerkship at a single institution. PARTICIPANTS: Third-year
      students. PROGRAM DESCRIPTION: Students reviewed an online module describing
      attributes of medical professionalism before completing a 4-step written exercise
      stimulated by viewing a work of art and based on a critical incident from their
      own experiences. A faculty member reviewed the essays and facilitated small group
      discussion to normalize the students' emotional responses and generalize their
      observations to others. PROGRAM EVALUATION: The curriculum was acceptable to
      students and enthusiastically received by faculty. Efforts to assess the effects
      and durability of the exercise on student behavior are ongoing. DISCUSSION:
      Artwork can enhance student reflection on professional values. This model
      efficiently and creatively meets curricular professionalism objectives.

PMID- 25850134
TI  - Dual process theory and intermediate effect: are faculty and residents'
      performance on multiple-choice, licensing exam questions different?
AB  - BACKGROUND: Clinical reasoning is essential for the practice of medicine. Dual
      process theory conceptualizes reasoning as falling into two general categories:
      nonanalytic reasoning (pattern recognition) and analytic reasoning (active
      comparing and contrasting of alternatives). The debate continues regarding how
      expert performance develops and how individuals make the best use of analytic and
      nonanalytic processes. Several investigators have identified the unexpected
      finding that intermediates tend to perform better on licensing examination items
      than experts, which has been termed the "intermediate effect." PURPOSE: We
      explored differences between faculty and residents on multiple-choice questions
      (MCQs) using dual process measures (both reading and answering times) to inform
      this ongoing debate. METHOD: Faculty (board-certified internists; experts) and
      residents (internal medicine interns; intermediates) answered live licensing
      examination MCQs (U.S. Medical Licensing Examination Step 2 Clinical Knowledge
      and American Board of Internal Medicine Certifying Examination) while being
      timed. We conducted repeated analysis of variance to compare the 2 groups on
      average reading time, answering time, and accuracy on various types of items.
      RESULTS: Faculty and residents did not differ significantly in reading time [F
      (1,35) = 0.01, p = 0.93], answering time [F (1,35) = 0.60, p = 0.44], or accuracy
      [F (1,35) = 0.24, p = 0.63] regardless of easy or hard items. DISCUSSION: Dual
      process theory was not evidenced in this study. However, this lack of difference
      between faculty and residents may have been affected by the small sample size of
      participants and MCQs may not reflect how physicians made decisions in actual
      practice setting.

PMID- 25850135
TI  - Development and initial validation of a program director's evaluation form for
      medical school graduates.
AB  - BACKGROUND: In the early 1990 s, our group of interdepartmental academicians at
      the Uniformed Services University (USU) developed a PGY-1 (postgraduate year 1)
      program director evaluation form. Recently, we have revised it to better align
      with the core competencies established by the Accreditation Council for Graduate
      Medical Education. We also included items that reflected USU's military-unique
      context. PURPOSE: To collect feasibility, reliability, and validity evidence for
      our revised survey. METHOD: We collected PGY-1 data from program directors (PD)
      who oversee the training of military medical trainees. The cohort of the present
      study consisted of USU students graduating in 2010 and 2011. We performed
      exploratory factor analysis (EFA) to examine the factorial validity of the survey
      scores and subjected each of the factors identified in the EFA to an internal
      consistency reliability analysis. We then performed correlation analysis to
      examine the relationship between PD ratings and students' medical school grade
      point averages (GPAs) and performance on U.S. Medical Licensing Examinations Step
      assessments. RESULTS: Five factors emerged from the EFA--Medical Expertise,
      Military-unique Practice, Professionalism, System-based Practice, and
      Communication and Interpersonal Skills." The evaluation form also showed good
      reliability and feasibility. All five factors were more strongly associated with
      students' GPA in the initial clerkship year than the first 2 years. Further,
      these factors showed stronger correlations with students' performance on Step 3
      than other Step Examinations. CONCLUSIONS: The revised PD evaluation form seemed
      to be a valid and reliable tool to gauge medical graduates' first-year internship
      performance.

PMID- 25850136
TI  - Development and initial validation of a program director's evaluation form for
      third-year residents.
AB  - BACKGROUND: Using a previously developed postgraduate year (PGY)-1 program
      director's evaluation survey, we developed a parallel form to assess more senior
      residents (PGY-3). The PGY-3 survey, which aligns with the core competencies
      established by the Accreditation Council for Graduate Medical Education, also
      includes items that reflect our institution's military-unique context. PURPOSE:
      To collect feasibility, reliability, and validity evidence for the new PGY-3
      evaluation. METHODS: We collected PGY-3 data from program directors who oversee
      the education of military residents. The current study's cohort consisted of
      Uniformed Services University of the Health Sciences students graduating in 2008,
      2009, and 2010. We performed exploratory factor analysis (EFA) to examine the
      internal structure of the survey and subjected each of the factors identified in
      the EFA to an internal consistency reliability analysis. We then performed
      correlation analysis to examine the relationships between PGY-3 ratings and
      several OUTCOMES: PGY-1 ratings, cumulative medical school grade point average
      (GPA), and performance on U.S. Medical Licensing Examinations (USMLE) Step 1,
      Step 2 Clinical Knowledge, and Step 3. RESULTS: Of the 510 surveys we
      distributed, 388 (76%) were returned. Results from the EFA suggested four
      factors: "Medical Expertise," "Professionalism," "Military-unique Practice," and
      "Systems-based Practice." Scores on these four factors showed good internal
      consistency reliability, as measured by Cronbach's alpha (alpha ranged from 0.92
      to 0.98). Further, as expected, "Medical Expertise" and "Professionalism" had
      small to moderate correlations with cumulative medical school GPA and performance
      on the USMLE Step examinations. CONCLUSIONS: The new program director's
      evaluation survey instrument developed in this study appears to be feasible, and
      the scores that emerged have reasonable evidence of reliability and validity in a
      sample of third-year residents.

PMID- 25850137
TI  - Career accomplishments of Uniformed Services University of the Health Sciences
      medical graduates: classes 1980-2001.
AB  - PURPOSE: To report accomplishments of graduates of the F. Edward Hebert School of
      Medicine who have left, retired, or are near the end of their uniformed career in
      several professional domains: military career milestones, medical professional
      education, academic landmarks, and leadership. METHODS: This study utilized an
      earlier questionnaire that was modified to capture additional career landmarks
      and improve the clarity of several items. The modified survey was sent
      electronically to alumni who graduated from 1980-2001 in March, 2012. RESULTS:
      The questionnaire was sent to 2,825 alumni for whom we had e-mail addresses. We
      estimate that we reached 2,400 alumni. A total of 1,189 alumni returned the
      questionnaire, yielding an estimated response rate of 50%. For this cohort, the
      board certification was 95%, over 20% obtained additional degrees, 92.8% had
      worked as a full-time physician, nearly two-thirds had deployed for combat, 13.9%
      had received the Legion of Merit, and 68.6% had published at least one peer
      reviewed manuscript. CONCLUSION: Many accomplishments including board
      certification rates, deployment experience, academic and military leadership
      positions, military awards, promotion rates, and academic medicine contributions
      are indicators that USU is continuing to meet its unique mission.

PMID- 25850138
TI  - Assessing curriculum effectiveness: a survey of Uniformed Services University
      medical school graduates.
AB  - PURPOSE: This study assessed alumni perceptions of their preparedness for
      clinical practice using the Accreditation Council for Graduate Medical Education
      (ACGME) competencies. We hypothesized that our alumni's perception of
      preparedness would be highest for military-unique practice and professionalism
      and lowest for system-based practice and practice-based learning and improvement.
      METHOD: 1,189 alumni who graduated from the Uniformed Services University (USU)
      between 1980 and 2001 completed a survey modeled to assess the ACGME competencies
      on a 5-point, Likert-type scale. Specifically, self-reports of competencies
      related to patient care, communication and interpersonal skills, medical
      knowledge, professionalism, systems-based practice, practice-based learning and
      improvement, and military-unique practice were evaluated. RESULTS: Consistent
      with our expectations as the nation's military medical school, our graduates were
      most confident in their preparedness for military-unique practice, which included
      items assessing military leadership (M = 4.30, SD = 0.65). USU graduates also
      indicated being well prepared for the challenges of residency education in the
      domain of professionalism (M = 4.02, SD = 0.72). Self-reports were also high for
      competencies related to patient care (M = 3.86, SD = 0.68), communication and
      interpersonal skills (M = 3.88, SD = 0.66), and medical knowledge (M = 3.78, SD =
      0.73). Consistent with expectations, systems-based practice (M = 3.50, SD = 0.70)
      and practice-based learning and improvement (M = 3.57, SD = 0.62) were the lowest
      rated competencies, although self-reported preparedness was still quite high.
      DISCUSSION: Our findings suggest that, from the perspective of our graduates, USU
      is providing both an effective military-unique curriculum and is preparing
      trainees for residency training. Further, these results support the notion that
      graduates are prepared to lead and to practice medicine in austere environments.
      Compared to other competencies that were assessed, self-ratings for systems-based
      practice and practice-based learning and improvement were the lowest, which
      suggests the need to continue to improve USU education in these areas.

PMID- 25850139
TI  - Relationship of neuroimaging to typical sleep times during a clinical reasoning
      task: a pilot study.
AB  - BACKGROUND: Sleep deprivation and fatigue have been associated with medical
      errors, clinical performance decrements, and reduced quality of life for both
      practicing physicians and medical students. Greater understanding of the impact
      of sleep quantity on clinical reasoning could improve patient care. The purpose
      of our pilot study was to examine relationships between clinical reasoning
      (assessed by functional magnetic resonance imaging) and sleep time (measured in
      different ways by actigraphy) while answering multiple-choice questions (MCQs)
      from licensing agencies. METHODS: Residents and faculty were administered a
      clinical reasoning exercise (MCQs from licensing bodies) during functional
      magnetic resonance imaging. Usual sleep patterns were sampled with actigraphy.
      Covariate analysis was used to examine the relationship between sleep duration
      (mean sleep, minimum sleep, maximum sleep) and brain activity during clinical
      reasoning (solving MCQs from licensing bodies). RESULTS: The mean sleep time over
      the duration of monitoring for the group was 7.19 hours (SD 0.66) with a range of
      6.1 to 8.1 hours (internal medicine faculty 7.1 hours, SD 0.41; internal medicine
      residents 7.27 hours, SD 0.92). There was a negative relationship between
      activation in the prefrontal cortex and minimum sleep time while reflecting on
      MCQs. CONCLUSION: Our findings provide evidence that the quantity of sleep can
      modulate brain activity while completing a clinically meaningful task that should
      be confirmed in larger studies. Our findings suggest that the construct of
      sleepiness may be more complex than appreciated by many and that the most
      important of these sleep measures in terms of outcomes remains to be determined.

PMID- 25850140
TI  - The place of USU among America's allies: reflections from the Surgeon General of
      the Canadian Armed Forces.

PMID- 25850141
TI  - Reassessing student potential for medical school success: distance traveled,
      grit, and hardiness.

PMID- 25850142
TI  - A model for teaching reflective practice.

PMID- 25850143
TI  - Leadership education and development at the Uniformed Services University.

PMID- 25850145
TI  - Academic change management: leadership lessons from curricular reform.

PMID- 25850144
TI  - Successful strategies for integrating bedside ultrasound into undergraduate
      medical education.
AB  - Nearly all physician specialties currently utilize bedside ultrasound, and its
      applications continue to expand. Bedside ultrasound is becoming a core skill for
      physicians; as such, it should be taught during undergraduate medical education.
      When ultrasound is integrated in a longitudinal manner beginning in the
      preclerkship phase of medical school, it not only enhances teaching the basic
      science topics of anatomy, physiology, and pathology but also ties those skills
      and knowledge to the clerkship phase and medical decision-making. Bedside
      ultrasound is a natural bridge from basic science to clinical science. The
      Uniformed Services University of the Health Sciences, F. Edward Hebert School of
      Medicine is currently in its fourth year of implementing an integrated ultrasound
      curriculum in the school of medicine. In our experience, successful integration
      of a bedside ultrasound curriculum should: align with unique focuses of a medical
      schools' mission, simplify complex anatomy through multimodal teaching, correlate
      to teaching of the physical examination, solidify understanding of physiology and
      pathology, directly link to other concurrent content, narrow differential
      diagnoses, enhance medical decision-making, improve procedural skills, match to
      year-group skillsets, develop teaching and leadership abilities, and have
      elective experiences for advanced topics. 

PMID- 25850146
TI  - Yes, but does it produce better doctors?

PMID- 25850147
TI  - Learning throughout a continuum, an innovative and feasible educational agenda!

PMID- 25850149
TI  - The Uniformed Services University of the Health Sciences: a leadership academy
      for military medical officers in the U.S. Navy.

PMID- 25850148
TI  - The long-term career outcome study: lessons learned and implications for
      educational practice.
AB  - The work of the Long-Term Career Outcome Study has been a program of scholarship
      spanning 10 years. Borrowing from established quality assurance literature, the
      Long-Term Career Outcome Study team has organized its scholarship into three
      phases; before medical school, during medical school, and after medical school.
      The purpose of this commentary is to address two fundamental questions: (1) what
      has been learned? and (2) how does this knowledge translate to educational
      practice and policy now and into the future? We believe that answers to these
      questions are relevant not only to our institution but also to other educational
      institutions seeking to provide high-quality health professions education. 

PMID- 25850150
TI  - The Uniformed Services University of the Health Sciences: developing career
      committed military medical officers.

PMID- 25850151
TI  - Measuring individual differences in driver inattention: further validation of the
      attention-related driving errors scale.
AB  - OBJECTIVE: The aim of this research was (a) to study driver inattention as a
      trait-like variable and (b) to provide new evidence of validity for the Attention
      Related Driving Errors Scale (ARDES). BACKGROUND: Driving inattention is
      approached from an individual differences perspective. We are interested in how
      drivers vary in their propensity to experience failures of attention and in the
      methods to measure these differences. METHOD: In a first sample (n = 301), we
      tested, via confirmatory factor analysis, a new theoretical model for the ARDES.
      In a second sample (n = 201), we evaluated the relationship between inattention
      and internal and external sources of distraction and social desirability bias in
      ARDES responses. A subsample (n = 65) was reevaluated to study temporal stability
      of the ARDES scores. RESULTS: Errors measured by the ARDES can be classified
      according to the driving task level at which they occur (navigation, maneuvering,
      or control). Differences in ARDES scores based on collision history were
      observed. ARDES was related to internal sources of distraction and was
      independent of the level of exposure to distracting activities. Test-retest
      showed a high degree of stability in ARDES scores. Low correlations were found
      with a social desirability measure. CONCLUSION: ARDES appears to measure a
      personal trait that remains relatively stable over time and is relatively
      independent of distracting activities. New evidence of validity emerged for this
      self-report. APPLICATION: ARDES can be used to measure individual differences in
      driving inattention and to help tailor preventive interventions for inattentive
      drivers. It can serve as an instrument of driver self-assessment in educational
      and training contexts.

PMID- 25850152
TI  - A comparison of abdominal muscle thickness changes after a lifting task in
      subjects with and without chronic low-back pain.
AB  - OBJECTIVE: Using ultrasound imaging, the abdominal muscles' response to the back
      extensor muscle fatigue was assessed in subjects with chronic low-back pain
      (CLBP). BACKGROUND: Lumbar muscle fatigue is a common occurrence among workers.
      Alteration in motor coordination is one consequence of muscular fatigue.
      According to previous studies, CLBP subjects use their back and abdominal muscles
      in different ways, but questions remain about abdominal muscle responses to back
      muscle fatigue in CLBP patients. METHOD: Thirteen CLBP patients and 15 healthy
      subjects participated in this study. The thickness of abdominal muscles-including
      transverse abdominis (TrA), internal oblique abdominis (IO), and external oblique
      abdominis (EO) muscles-was measured in standing position with and without axial
      loads before and after a lifting fatigue task. RESULTS: The results reveal a
      significant difference for the main effects of group on percentage of change in
      TrA thickness (F = 8.9, p = .004). Percentage of change in thickness of TrA was
      10% greater in the CLBP group. Although IO thickness displayed greater percentage
      of change in the CLBP group, the difference between groups was not significant.
      CONCLUSION: Abdominal muscle behavior changes with back-muscle fatigue in both
      healthy and CLBP subjects, but responses were more exaggerated in CLBP patients.
      APPLICATION: Ultrasound imaging technique can provide critical information about
      the effect of fatigue on spinal muscle activation and consequently about the
      stability of the spine. As a more applicable and easy technique, ergonomists can
      use ultrasound imaging in musculoskeletal system assessment in worker populations
      in future studies.

PMID- 25850153
TI  - Effects of carrying a backpack in an asymmetrical manner on the asymmetries of
      the trunk and parameters defining lateral flexion of the spine.
AB  - OBJECTIVE: The aim of this study was to examine changes in the body posture
      parameters defining asymmetry of the trunk and lateral flexion of the spine in
      children while carrying a backpack weighing 10% of a child's weight. BACKGROUND:
      Carrying a backpack may negatively affect the posture of schoolchildren and
      contribute to spinal pain. METHOD: The study involved 162 primary school students
      ages 11 to 13 years. The parameters describing body posture were assessed with a
      backpack carried on the right or left shoulder as well as without a load. To
      assess the predefined parameters, we used the CQ Elektronik System, employing the
      photogrammetric method. RESULTS: Trunk inclination shifted significantly in the
      opposite direction to the shoulder the backpack was carried on, and an increase
      in shoulder asymmetry was also found. We also observed a more pronounced right
      side lateral flexion of the spine when the backpack was carried on the right
      shoulder and an analogous relationship for the left side. CONCLUSION: The results
      of this study show that carrying a backpack in an asymmetrical manner negatively
      affects spine, even if the backpack weight constitutes 10% of the child's weight,
      which has been previously recommended as a safe load for a child's shoulders.
      APPLICATION: We suggest that the issue of safe backpack weight be reassessed and
      that students be taught basic ergonomic principles on how to carry loads. Changes
      to the management pattern of carrying textbooks to and from school also should be
      considered.

PMID- 25850154
TI  - Multiaxis grip characteristics for varying handle diameters and effort.
AB  - OBJECTIVE: A multiaxis dynamometer was used to quantify grip force vector angles
      and longitudinal centers of pressure (COPs) while varying handle size and effort
      used. BACKGROUND: Authors of many studies have examined maximum grip strength
      using scalar instruments; a few have measured two-axis forces limited to one or
      more finger contact. This novel dynamometer uses two instrumented beams that are
      grasped by the distal fingers and proximal palm to compute two orthogonal
      components of force and the longitudinal COP through which the force acts.
      METHOD: Sixteen healthy, right-handed participants grasped the multiaxis
      dynamometer with plastic handles ranging in diameter from 3.81 to 7.62 cm. They
      were required to scale their effort to 25%, 50%, 75%, and 100% of maximum.
      RESULTS: Grip force vector angles were affected by both handle diameter and
      effort level, with angles increasing an average of 8.1 degrees  from the least to
      greatest effort. Longitudinal COP, averaged among the two beams, shifted 1.75 cm
      radially as handle diameter increased from 3.81 cm to 7.62 cm. Average COP along
      the beam in contact with the distal finger segments shifted 0.75 cm ulnarly as
      effort level increased from 25% to 100% of maximum. CONCLUSION: Grip force
      characteristics changed with handle diameter and effort level. Overall grip force
      magnitude comprised both force components measured. APPLICATION: Understanding
      grip characteristics should be important for handle and grip design and for
      evaluating hand function.

PMID- 25850155
TI  - Arm and neck pain in ultrasonographers.
AB  - OBJECTIVE: The aim of this study was to evaluate the prevalence of upper-body
      quadrant pain among ultrasonographers and to evaluate the association between
      individual ergonomics, musculoskeletal disorders, and occurrence of neck pain.
      METHOD: A hundred and ten (N = 110) Belgian and Dutch male and female hospital
      ultrasonographers were consecutively enrolled in the study. Data on work-related
      ergonomic and musculoskeletal disorders were collected with an electronic
      inquiry, including questions regarding ergonomics (position of the screen, high
      low table, and ergonomic chair), symptoms (neck pain, upper-limb pain), and work
      related factors (consecutive working hours a day, average working hours a week).
      RESULTS: Subjects with the screen on their left had significantly more neck pain
      (odds ratio [OR] = 3.6, p = .0286). Depending on the workspace, high-low tables
      increased the chance of developing neck pain (OR = 12.9, p = .0246). A screen at
      eye level caused less neck pain (OR = .22, p = .0610). Employees with a fixed
      working space were less susceptible to arm pain (OR = 0.13, p = .0058). The
      prevalence of arm pain was significantly higher for the vascular department
      compared to radiology, urology, and gynecology departments (OR = 9.2, p = .0278).
      CONCLUSIONS: Regarding prevention of upper-limb pain in ultrasonograph, more
      attention should be paid to the work environment and more specialty to the
      ultrasound workstation layout. Primary ergonomic prevention could provide a
      painless work situation for the ultrasonographer. APPLICATION: Further research
      on the ergonomic conditions of ultrasonography is necessary to develop ergonomic
      solutions in the work environment that will help to alleviate neck and arm pain.

PMID- 25850156
TI  - Sideways camera rotations of 90 degrees  and 135 degrees  result in poorer
      performance of laparoscopic tasks for novices.
AB  - OBJECTIVE: The aim of this study was to determine the impact of sideways
      visuomotor rotations between 0 degrees  and 180 degrees  on novice performance in
      a laparoscopic simulator. BACKGROUND: The laparoscopic surgical environment often
      involves visuomotor rotations because the laparoscope may be placed to the
      surgeon's side. Basic research by Cunningham indicated that visuomotor rotations
      between 90 degrees  and 135 degrees  result in peak performance decrements.
      Research by Ames and colleagues failed to replicate Cunningham's results in the
      laparoscopic environment, possibly due to (a) confounds from carryover effects or
      (b) use of an alternative laparoscopic training task rather than the straight
      line pointing task used by Cunningham. Two experiments were conducted to
      determine if Cunningham's results generalize to the laparoscopic environment when
      controlling for carryover effects for a three-dimensional "straight-line"
      pointing task (Experiment 1) and a laparoscopic training task (Experiment 2).
      METHOD: In Experiments 1 and 2, participants were assigned to one of five
      visuomotor rotations: 0 degrees , 45 degrees , 90 degrees , 135 degrees , or 180
      degrees . Utilizing a laparoscopic simulator, participants performed either a
      three-dimensional pointing task (Experiment 1) or a peg transfer task (Experiment
      2). RESULTS: In both experiments, visuomotor rotations of 90 degrees  or 135
      degrees  resulted in the poorest performance. CONCLUSION: When controlling for
      carryover effects, Cunningham's results generalize to novices' performance of a
      pointing and a peg transfer task in the laparoscopic environment. APPLICATIONS:
      The results indicate that 90 degrees  and 135 degrees  sideways laparoscope
      placements may result in worse performance for novices in the laparoscopic
      environment, indicating potentially longer learning curves for these conditions
      in the laparoscopic as well as other teleoperation environments.

PMID- 25850157
TI  - Musculoskeletal disorder symptoms in correction officers: why do they increase
      rapidly with job tenure?
AB  - OBJECTIVE: In this study, we sought to explain the rapid musculoskeletal
      symptomatology increase in correction officers (COs). BACKGROUND: COs are exposed
      to levels of biomechanical and psychosocial stressors that have strong
      associations with musculoskeletal disorders (MSDs) in other occupations, possibly
      contributing to their rapid health deterioration. METHOD: Baseline survey data
      from a longitudinal study of COs and manufacturing line workers were used to
      model musculoskeletal symptom prevalence and intensity in the upper (UE) and
      lower (LE) extremity. Outcomes were regressed on demographics and biomechanical
      and psychosocial exposures. RESULTS: COs reported significantly higher prevalence
      and intensity of LE symptoms compared to the industrial workers. In regression
      models, job tenure was a primary driver of CO musculoskeletal outcomes. In CO
      models, a single biomechanical exposure, head and arms in awkward positions,
      explained variance in both UE and LE prevalence (beta of 0.338 and 0.357,
      respectively), and low decision latitude was associated with increased LE
      prevalence and intensity (beta of 0.229 and 0.233, respectively). Manufacturing
      models were less explanatory. Examining demographic associations with exposure
      intensity, we found none to be significant in manufacturing, but in CO models,
      important psychosocial exposure levels increased with job tenure. CONCLUSION:
      Symptom prevalence and intensity increased more rapidly with job tenure in
      corrections, compared to manufacturing, and were related to both biomechanical
      and psychosocial exposures. Tenure-related increases in psychosocial exposure
      levels may help explain the CO symptom increase. APPLICATION: Although exposure
      assessment improvements are proposed, findings suggest focusing on improving the
      psychosocial work environment to reduce MSD prevalence and intensity in
      corrections.

PMID- 25850158
TI  - Visual information processing from multiple displays.
AB  - OBJECTIVE: In this study, we examined how effectively people can monitor new
      stimuli on a peripheral display while carrying out judgments on an adjacent
      central display. BACKGROUND: Improved situation awareness is critical for
      improved operator performance in aviation and many other domains. Given the
      limited extent of foveal processing, acquiring additional information from
      peripheral vision offers high potential gains. METHOD: Participants carried out a
      sequence of central perceptual judgments while simultaneously monitoring the
      periphery for new stimuli. Peripheral detection was measured as a function of
      central-judgment difficulty, the relative timing of the two tasks, and peripheral
      event rate. RESULTS: Participants accurately detected and located peripheral
      targets, even at the highest eccentricity explored here (~30 degrees ).
      Peripheral detection was not reduced by increased central-task difficulty but was
      reduced when peripheral targets arrived later in the processing of central
      stimuli and when peripheral events were relatively rare. CONCLUSION: Under
      favorable conditions-high-contrast stimuli and high event rate-people can
      successfully monitor peripheral displays for new events while carrying out an
      unrelated continuous task on an adjacent display. APPLICATION: In many fields,
      such as aviation, existing displays were designed with low-contrast stimuli that
      provide little opportunity for peripheral vision. With appropriate redesign,
      operators might successfully monitor multiple displays over a large visual field.
      Designers need to be aware of nonvisual factors, such as low event rate and
      relative event timing, that can lead to failures to detect peripheral stimuli.

PMID- 25850159
TI  - Situation awareness measures for simulated submarine track management.
AB  - OBJECTIVE: The aim of this study was to examine whether the Situation Present
      Assessment Method (SPAM) and the Situation Awareness Global Assessment Technique
      (SAGAT) predict incremental variance in performance on a simulated submarine
      track management task and to measure the potential disruptive effect of these
      situation awareness (SA) measures. BACKGROUND: Submarine track managers use
      various displays to localize and track contacts detected by own-ship sensors. The
      measurement of SA is crucial for designing effective submarine display interfaces
      and training programs. METHOD: Participants monitored a tactical display and
      sonar bearing-history display to track the cumulative behaviors of contacts in
      relationship to own-ship position and landmarks. SPAM (or SAGAT) and the Air
      Traffic Workload Input Technique (ATWIT) were administered during each scenario,
      and the NASA Task Load Index (NASA-TLX) and Situation Awareness Rating Technique
      were administered postscenario. RESULTS: SPAM and SAGAT predicted variance in
      performance after controlling for subjective measures of SA and workload, and SA
      for past information was a stronger predictor than SA for current/future
      information. The NASA-TLX predicted performance on some tasks. Only SAGAT
      predicted variance in performance on all three tasks but marginally increased
      subjective workload. CONCLUSION: SPAM, SAGAT, and the NASA-TLX can predict unique
      variance in submarine track management performance. SAGAT marginally increased
      subjective workload, but this increase did not lead to any performance decrement.
      APPLICATION: Defense researchers have identified SPAM as an alternative to SAGAT
      because it would not require field exercises involving submarines to be paused.
      SPAM was not disruptive, but it is potentially problematic that SPAM did not
      predict variance in all three performance tasks.

PMID- 25850160
TI  - Driving speed of young novice and experienced drivers in simulated hazard
      anticipation scenes.
AB  - OBJECTIVE: In this study, we aimed to demonstrate analysis methods that are
      sensitive to speed-related differences between experienced and young novice
      drivers. These differences may be linked to determining which group is better at
      anticipating hazards. BACKGROUND: Awareness of hazardous situations, especially
      potential ones, is a major discriminator between experienced and young novice
      drivers who tend to misidentify potential hazards in the traffic environment.
      METHOD: Experienced and young novice drivers were asked to drive a sequence of 14
      scenarios in a driving simulator. Scenarios were created in two city areas,
      residential and business district, and included various types of hazards. Group
      homogeneity of speed for each group of drivers was computed for each scenario,
      and two business district scenarios were subjected to piecewise linear regression
      analysis. RESULTS: Group homogeneity analysis showed consistent and significant
      experience-based differences across all scenarios, revealing that the experienced
      drivers as a group were more homogenous in choosing their driving speed.
      Differences between groups were larger in the business district where speed was
      less restricted. Piecewise linear regression analysis revealed that experienced
      drivers approached uncontrolled intersections by slowing down and responded
      earlier to materialized events. CONCLUSION: Young novice drivers were more likely
      than experienced drivers to choose diverse values of speed at any given road
      section, presumably due to their poor awareness of potential and hidden hazards.
      Unlike other analysis methods, it is argued that group homogeneity of speed is a
      more sensitive measurement to reveal these gaps. APPLICATION: Speed management
      could be the basis of future hazard anticipation simulator assessments.

PMID- 25850161
TI  - Dynamic vibrotactile signals for forward collision avoidance warning systems.
AB  - OBJECTIVE: Four experiments were conducted in order to assess the effectiveness
      of dynamic vibrotactile collision-warning signals in potentially enhancing safe
      driving. BACKGROUND: Auditory neuroscience research has demonstrated that
      auditory signals that move toward a person are more salient than those that move
      away. If this looming effect were found to extend to the tactile modality, then
      it could be utilized in the context of in-car warning signal design. METHOD: The
      effectiveness of various vibrotactile warning signals was assessed using a
      simulated car-following task. The vibrotactile warning signals consisted of
      dynamic toward-/away-from-torso cues (Experiment 1), dynamic versus static
      vibrotactile cues (Experiment 2), looming-intensity- and constant-intensity
      toward-torso cues (Experiment 3), and static cues presented on the hands or on
      the waist, having either a low or high vibration intensity (Experiment 4).
      RESULTS: Braking reaction times (BRTs) were significantly faster for toward-torso
      as compared to away-from-torso cues (Experiments 1 and 2) and static cues
      (Experiment 2). This difference could not have been attributed to differential
      responses to signals delivered to different body parts (i.e., the waist vs.
      hands; Experiment 4). Embedding a looming-intensity signal into the toward-torso
      signal did not result in any additional BRT benefits (Experiment 3). CONCLUSION:
      Dynamic vibrotactile cues that feel as though they are approaching the torso can
      be used to communicate information concerning external events, resulting in a
      significantly faster reaction time to potential collisions. APPLICATION: Dynamic
      vibrotactile warning signals that move toward the body offer great potential for
      the design of future in-car collision-warning system.

PMID- 25850162
TI  - Reading text while driving: understanding drivers' strategic and tactical
      adaptation to distraction.
AB  - OBJECTIVE: In this study, we investigated how drivers adapt secondary-task
      initiation and time-sharing behavior when faced with fluctuating driving demands.
      BACKGROUND: Reading text while driving is particularly detrimental; however, in
      real-world driving, drivers actively decide when to perform the task. METHOD: In
      a test track experiment, participants were free to decide when to read messages
      while driving along a straight road consisting of an area with increased driving
      demands (demand zone) followed by an area with low demands. A message was made
      available shortly before the vehicle entered the demand zone. We manipulated the
      type of driving demands (baseline, narrow lane, pace clock, combined), message
      format (no message, paragraph, parsed), and the distance from the demand zone
      when the message was available (near, far). RESULTS: In all conditions, drivers
      started reading messages (drivers' first glance to the display) before entering
      or before leaving the demand zone but tended to wait longer when faced with
      increased driving demands. While reading messages, drivers looked more or less
      off road, depending on types of driving demands. CONCLUSIONS: For task
      initiation, drivers avoid transitions from low to high demands; however, they are
      not discouraged when driving demands are already elevated. Drivers adjust time
      sharing behavior according to driving demands while performing secondary tasks.
      Nonetheless, such adjustment may be less effective when total demands are high.
      APPLICATION: This study helps us to understand a driver's role as an active
      controller in the context of distracted driving and provides insights for
      developing distraction interventions.

PMID- 25850163
TI  - Suggested methods to improve physician-hospital relationships in Canada.
AB  - This article focuses on the suggested methods to improve the quality of Physician
      Hospital Relations (PHRs) in the Canadian healthcare system based on the opinions
      and perspectives of healthcare leaders across all provinces and territories who
      participated in the Canadian National Study of Interprofessional Relationships
      between Physicians and Hospital Administrators (CANSIRPH). Improving PHRs equals
      higher patient care quality, error reduction, well-managed budgets, and
      professional satisfaction of clinical and non-clinical leaders.

PMID- 25850164
TI  - The owners have a right to be heard: Patient voice in design and performance
      improvement.
AB  - The Canadian taxpayer is an owner of the healthcare system and the owners have a
      right to be heard. This article encourages leaders both formal and informal to
      create cultures that promote ASKing questions to test assumptions held, LISTENing
      to hear the patient voice, and TALKing with patients and families to create new
      conversations and narratives. Looking at the label, "healthcare system" what's
      your contribution to creating health, how will you dedicate yourself to caring
      about the healthcare consumer and care provider, and what will be your role in
      creating a new and improved system? An implied question at the foundation of the
      article is this: Is the difference between managing and leading a difference of
      empathy?

PMID- 25850165
TI  - Health leaders and ethical dimensions of managing "value adds".
AB  - Value adds refers to an "extra" feature or features of an item of interest
      (product, service, and person) that go beyond the standard expectations and
      provide something more, even if the cost is higher to the client or purchaser.
      This article looks at the ethical dimensions health leaders face in managing
      value adds and provides recommendations for ensuring that ethical practice is
      being followed consistently. A summary of several healthcare-related codes of
      ethics are provided to support the recommendations.

PMID- 25850166
TI  - In vivo phytochrome-mediated perception of reflected light signals.
AB  - The spectrophotometric assay of phytochrome in vivo in etiolated plant material
      was used to determine the effects of changes in reflected light on the state of
      the photoreceptor in etiolated seedlings exposed simultaneously to direct and
      reflected light. Changes in reflected light that were small in terms of the total
      (direct + reflected) radiation incident on the seedlings produced detectable
      changes in the state of phytochrome in vivo. The contribution of reflected light
      to the state of phytochrome in vertical organs was greater than expected from its
      low contribution to total incident light. These data from laboratory studies
      complement and are consistent with results of field studies on the effects of
      light reflected from neighboring vegetation on plant growth under natural
      radiation conditions.

PMID- 25850167
TI  - The luck of the new graduate nurse.

PMID- 25850168
TI  - Nurse wants action on pay and superannuation.

PMID- 25850169
TI  - Five-pointed star article praised.

PMID- 25850170
TI  - How is your medal holding on?

PMID- 25850172
TI  - The Kaiwhakahaere comments.

PMID- 25850171
TI  - Valuing all human life.

PMID- 25850173
TI  - Slow progress in MECA negotiations.

PMID- 25850174
TI  - Care rationing 'untenable'.

PMID- 25850175
TI  - Supreme Court declines appeal on equal pay case.

PMID- 25850176
TI  - Student enrolments steady.

PMID- 25850177
TI  - Evaluation recommends CCDM in all DHBs.

PMID- 25850178
TI  - Rates of older women in the workforce increasing.

PMID- 25850180
TI  - Masked tutor brings patient to 'life'.

PMID- 25850179
TI  - What nurses think about professionalism.

PMID- 25850181
TI  - How well do new graduates manage medications?

PMID- 25850182
TI  - Peer supervision requires ongoing commitment.

PMID- 25850184
TI  - Knowing your legislation.

PMID- 25850183
TI  - Osteoporosis--fragile bones.

PMID- 25850185
TI  - Comparing nursing competencies.

PMID- 25850186
TI  - Why we should value younger nurses.

PMID- 25850187
TI  - Hinerangi's legacy lives on.

PMID- 25850189
TI  - Mentoring, technology, team work, history.

PMID- 25850188
TI  - Building the Maori nursing workforce.

PMID- 25850190
TI  - Primary health care: MECA overwhelmingly endorsed.

PMID- 25850191
TI  - DHBs: new birthing service in Buller but closure in Stratford.

PMID- 25850192
TI  - Private hospitals: hospice MECA underway.

PMID- 25850193
TI  - Aged care: extra government money not going to Radius staff.

PMID- 25850194
TI  - Perioperative nursing: OR education.

PMID- 25850195
TI  - Dermatological and cosmeceutical benefits of Glycine max (soybean) and its active
      components.
AB  - Glycine max, known as the soybean or soya bean, is a species of legume native to
      East Asia. Soya beans contain many functional components including phenolic
      acids, flavonoids, isoflavonoids (quercetin, genistein, and daidzein), small
      proteins (Bowman-Birk inhibitor, soybean trypsin inhibitor) tannins, and
      proanthocyanidins. Soybean seeds extract and fresh soymilk fractions have been
      reported to possess the cosmeceutical and dermatological benefits such as anti
      inflammatory, collagen stimulating effect, potent anti-oxidant scavenging peroxyl
      radicals, skin lightening effect and protection against UV radiation. Thus,
      present review attempts to give a short overview on dermatological and
      cosmeceutical studies of soybean and its bioactive compounds.

PMID- 25850196
TI  - The role of prostanoids in the urinary bladder function and a potential use of
      prostanoid-targeting pharmacological agents in bladder overactivity treatment.
AB  - Overactive bladder (OAB) is a syndrome involving urinary urgency with
      accompanying increased daytime urinary frequency and nocturia, with or without
      urgency urinary incontinence, in the absence of an urinary tract infection or
      other obvious pathology. The detailed OAB pathophysiology remains unclear. There
      is evidence that OAB pathogenesis also includes abnormal bladder paracrine
      activity, associated with release of local prostanoids. Those agents contribute
      to disturbances of peripheral neuronal bladder control resulting in detrusor
      instability. Thus, pharmacological agents abolishing prostanoid-induced bladder
      overactivity seem to be a potential, future OAB therapeutical option. This paper
      shortly describes the rationale for nonsteroidal antiinflammatory drugs (NSAIDs)
      and EP-1 receptor antagonists administration in future OAB pharmacotherapy.

PMID- 25850197
TI  - Solid state characterization of alpha-tocopherol in inclusion complexes with
      cyclodextrins.
AB  - The alternative for a pure soluble, sensible for physical and chemical conditions
      oil form of alpha-tocopherol (alpha-T) is its complexation with cyclodextrins. A
      different influence of cyclodextrins on the included substance demands a
      stability investigation of the substance enclosed in a host-guest complex. Hence,
      the thermal stability of alpha-T in inclusion complexes (InCs) with cyclodextrins
      (CDs) was studied. The inclusion complexes were obtained by two different
      methods: a lyophilization and a kneading method, and their formation was examined
      by IR spectroscopy, differential scanning calorimetry and 1H-NMR spectroscopy.
      The inclusion complexes were subjected to the test of accelerated aging at 323 K,
      333 K, 338 and 343 K, for comparison alpha-T as a substance and physical mixtures
      (PhM) of alpha-T with CDs were used. Changes in alpha-T concentration during the
      experiment were followed by HPLC method and next, the products of thermal
      decomposition were studied by LC-ESI-MS/MS method. The reaction of alpha-T
      decomposition in inclusion complexes with CDs was found to be of the first order.
      The same order of a decomposition reaction was observed in a sample of alpha-T as
      a substance. It seems that cyclodextrins protect alpha-T against thermal
      decomposition, moreover, the protective effect of natural beta-cyclodextrin (beta
      CD) appears to be greater than that of 2-hydroxypropyl-beta-cyclodextrin (2-HP
      beta-CD). However, the CDs do not influence the type of a formed product of
      decomposition. This product, i.e., the dimer of alpha-T (m/z 859 Da), was found
      in all tested samples. The protective effect of CDs and transformation from the
      liquid state to the solid state of alpha-T can be used to create a new
      pharmaceutical form--tablets with alpha-T.

PMID- 25850198
TI  - Determination of neomycin in the form of neomycin derivative with dabsyl chloride
      by thin layer chromatography and densitometry.
AB  - A thin layer chromatographic-densitometric method has been developed for
      identification and quantitative determination of neomycin derivative with dabsyl
      chloride. The analysis of antibiotic was achieved on the silica gel TLC plates
      with fluorescent indicator with n-butanol--2-butanone--25% ammonia--water (10 : 6
      : 2 : 2, v/v/v/v) as the mobile phase. The densitometric measurements were made
      at 460 nm. Under these conditions good separation of chosen aminoglycoside
      antibiotic from reagent used to make a complex was obtained. The method is
      characterized by high sensitivity, LOD from 0.1953 MUg per band and LOQ from
      0.5918 MUg per band, wide linearity range from 0.5918 to 2.1960 MUg per band for
      neomycin. The precision of the method was good; RSD varied from 1.17 to 2.05%.
      Satisfactory results of validation of the method were also confirmed by
      determination of selected antibiotic in pharmaceutical commercial preparation.
      The results obtained by TLC-densitometric method were compared with those
      obtained by spectrophotometric method.

PMID- 25850199
TI  - Effect of chromatographic conditions on retention behavior and system efficiency
      for HPTLC of selected psychotropic drugs on chemically bonded stationary phases.
AB  - Selected psychotropic drug standards have been chromatographed on RP18, CN and
      diol layers with a variety of aqueous and nonaqueous mobile phases. The effect of
      buffers at acidic or basic pH, acetic acid, ammonia and diethylamine (DEA) in
      aqueous mobile phases on retention, efficiency and peak symmetry was examined.
      Improved peak symmetry and separation selectivity for investigated compounds were
      observed when ammonia or DEA were used as mobile phase additives. The effect of
      diethylamine concentration in aqueous eluents on retention, peak symmetry and
      theoretical plate number obtained on CN plates was also investigated. Because of
      the strong retention of these basic drugs on stationary phases bonded on silica
      matrix, nonaqueous eluents containing medium polar diluents, strongly polar
      modifiers and silanol blockers (ammonia or diethylamine) were applied. Aqueous
      and nonaqueous eluent systems with the best selectivity and efficiency were used
      for separate psychotropic drug standards' mixture on CN layer by 2D TLC.

PMID- 25850200
TI  - The effect of lipoic acid administration on the urinary excretion of thiocyanate
      in rats exposed to potassium cyanide.
AB  - The oxidation of cyanide (CN-) to a much less toxic thiocyanate (SCN-) is the
      main in vivo biochemical pathway for CN- detoxification. SCN- is excreted mainly
      in urine. This study was performed to investigate the effect of lipoic acid (LA)
      on the urinary excretion of thiocyanate (SCN-; rhodanate) in rats. Groups of the
      animals were treated intraperitoneally (i.p.) as follows: group 1: potassium
      cyanide (KCN) (1 mg/kg); group 2: KCN (1 mg/kg) + LA (100 mg/kg). Urine was
      collected for 24 h and the pooled samples were examined for SCN- levels. The
      obtained results indicated that the treatment of animals with potassium cyanide
      and LA in combination significantly increased the urinary excretion of SCN- in
      comparison with the respective values in the KCN-alone-treated group. It
      indicates that LA increased the rate of CN- detoxification in rats.

PMID- 25850201
TI  - Synthesis and antibacterial properties of pyrimidine derivatives.
AB  - In this study, a series of syntheses was conducted on the pyrimidine system,
      obtaining bisulfite carboxyl derivatives 4 and hydroxy derivatives 5. In
      addition, a series of syntheses were carried out as a result of which both alkyl
      and aromatic amines were obtained. Then, the attempt was made to cyclize these
      amines in the Mannich reaction to pyrimido[4,5-d]pyrimidines 11, 12. After
      determination of chemical structure using physicochemical tests, also by means of
      crystallographic tests, all the newly obtained derivatives underwent
      microbiological tests on bacterial strains and fungi. The most interesting
      results of the microbiological tests are included later in the study.

PMID- 25850202
TI  - Novel pyrrolopyrimidines and triazolopyrrolopyrimidines carrying a biologically
      active sulfonamide moieties as anticancer agents.
AB  - A new series of pyrroles 5, 6, pyrrolopyrimidines 8, 11-14, 16-29, triazolo
      pyrrolopyrimidines 9, 10 and 15 carrying a biologically active sulfonamide
      moities were synthesized using 2-amino-3-cyano-4-(4-bromophenyl)pyrrole 5 as a
      strategic starting material. The structures of the prepared compounds were
      confirmed by elemental analyses, IR, 1H-NMR and 13C-NMR data. All of the
      synthesized compounds showed promising anticancer activity against breast cancer
      cell line (MCF7) compared to doxorubicin as reference drug, especially compounds
      5-17, 21-24 and 28 with better IC50 than that of doxorubicin. In order to suggest
      the mechanism of action of their cytotoxic activities, molecular docking on the
      active site of c-Src was done and good results were obtained.

PMID- 25850203
TI  - Cytotoxic activity of some novel sulfonamide derivatives.
AB  - The versatile synthons 2-chloro-N-(4-sulfamoylphenyl)acetamides la,b were used as
      a key intermediates for the synthesis of sulfonamide derivatives with adamantyl
      2, indene 3, morpholinophenyl 4, pipronyl 5, benzothiazole 6-8, pyrazole 9,
      thiadiazole 10,11, quinoline 12, isoquinoline 13, thiazoles 14-19, acrylamides 20
      24 and benzochromene 25 moieties via reaction with several nitrogen nucleophiles.
      The newly synthesized compounds were screened in vitro for their anticancer
      activity against breast cancer (MDA-MB-231) and colon cancer (HT-29) cell lines.
      Compound 17 was found to be the most potent against breast cancer cell lines with
      IC55 value 66.6 MUM compared with the reference drug 5-fluorouracil with IC50
      value 77.28 MUM.

PMID- 25850204
TI  - Synthesis and evaluation of anticonvulsant activity of N-(2,5-dimethylphenoxy)-
      and N-[(2,3,5-trimethylphenoxy)alkyl]aminoalkanols.
AB  - A series of new N-(2,5-dimethylphenoxy)- and N-(2,3,5
      trimethylphenoxy)alkylaminoalkanols [I-XVII] was synthesized and evaluated for
      anticonvulsant activity. Pharmacological tests included maximal electroshock
      (MES) and subcutaneous pentetrazole seizure threshold (scMet) assays as well as
      neurotoxicity (TOX) evaluation in mice after intraperitoneal (i.p.)
      administration and/or in rats after oral (p.o.) administration. The most active
      compound was R-2N-[(2,3,5-trimethylphenoxy)ethyl]aminobutan-1-ol, which exhibited
      100% activity in MES at the dose of 30 mg/kg body weight (mice, i.p.) and 75%
      activity in MES at 30 mg/kg b.w. (rats, p.o.) without neurotoxicity at the active
      doses.

PMID- 25850205
TI  - Synthesis and antiproliferative activity in vitro of new 2-thioxoimidazo[4,5
      B]pyridine derivatives.
AB  - Two series of 2-thioxoimidazo[4,5-b]pyridine derivatives have been synthesized
      from 2,3-diaminopyridine (1) and 5-halogenosubstituted-2,3-diaminopyridines 2, 3.
      Mannich bases 7 - 12 and 24 - 29, derivatives of 1-arylamino-6-halogeno-2
      thioxoimidazo[4,5-b]pyridine were obtained with selected secondary amines:
      morpholine, piperidine, 2-methoxyphenylpiperazine, pyrimidyn-2-yl-piperazine and
      formaldehyde in ethanol. The structures 7 - 12 and 24 - 29 were confirmed by the
      results of elementary analysis and their IR, 1H-NMR and MS spectra. All given
      structures 7 - 12 have been optimized to get the most stable low energy
      conformers. Synthesized compounds were of interest for biological studies or can
      be substrates for further synthesis. The selected compounds 7 - 10, 12- 17, 22,
      25, 27 - 29 were screened for their antiproliferative activity in vitro against
      human cancer and normal mouse fibroblast cell lines.

PMID- 25850206
TI  - Evaluation of anti-inflammatory, analgesic and antipyretic activities of Thymus
      serphyllum Linn. in mice.
AB  - The present study was conducted to evaluate the analgesic, anti-inflammatory and
      antipyretic activities of Thymus serphyllum Linn. in mice. Anti-inflammatory
      activity was evaluated by carrageenan and egg albumin induced paw edema in mice,
      while analgesic activity was assessed using formalin induced paw licking and
      acetic acid induced abdominal writhing in mice. For determination of antipyretic
      activity, pyrexia was induced by subcutaneous injection of 20% yeast. All the
      extracts produced significant anti-inflammatory effect however, ether extract
      produced maximum effect 34% inhibition (p < 0.001) against carrageenan and 22% (p
      < 0.01) inhibition against egg albumin induced paw edema in mice at the end of 3
      h. Ether extract produced prominent analgesic effect 77% (p < 0.001) inhibition
      in acetic acid induced abdominal writhing and 59% inhibition in formalin induced
      paw licking model in mice, respectively. Ether extract also demonstrated
      significant (p < 0.001) antipyretic activity against yeast induced pyrexia. The
      plant showed no sign of toxicity up to the dose of 2000 mg/kg in mice. This study
      supports the use of Thymus serphyllum in traditional medicine for inflammation
      accompanied by pain and fever.

PMID- 25850207
TI  - In vitro antioxidant activity and GC-MS analysis of the ethanol and aqueous
      extracts of Cissus cornifolia (Baker) Splanch (Vitaceae) parts.
AB  - The study was intended to explore the antioxidant potential and phytochemical
      content of the ethanol and aqueous extracts of the leaf and root samples of
      Cissus cornifolia (Baker) Splanch (Vitaceae) across a series of four in vitro
      models. The results showed that all the extracts had reducing power (Fe(3+) -
      Fe2+) and DPPH, hydroxyl and nitric oxide radical scavenging abilities to varying
      extents. However, the ethanol root extract had more potent antioxidant power in
      all the experimental models than other extracts and possessed a higher total
      phenol content of 136.1 +/- 6.7 mg/g. The GC-MS analysis of the aqueous and
      ethanol extracts of the roots indicated the presence of the common aromatic
      phenolic compounds, pyrogallol, resorcinol and catechol, a fatty acid, n
      hexadecanoic acid and an aldehyde, vanillin. Data from this study suggest that
      both the leaves and roots of C. cornifolia possessed anti-oxidative activities
      with the best anti-oxidant activity being exhibited by the ethanolic extract of
      the root. The antioxidant properties of the root extracts can be attributed to
      the phenolic compounds present in the extracts.

PMID- 25850208
TI  - Diuretic activity of aqueous extract of Nigella sativa in albino rats.
AB  - The study aims to evaluate the diuretic effect and acute toxicity of a crude
      aqueous extract of Nigella sativa using animal models. To evaluate the diuretic
      activity of the plant, Albino rats were divided into five groups. The control
      group received normal saline (10 mL/kg), the reference group received furosemide
      (10 mg/kg) and the test groups were administered different doses (i.e., 10, 30
      and 50 mg/kg) of the crude extract by intra-peritoneal route, respectively. Graph
      Pad Prism was used for the statistical analysis and p-values less than 0.05 were
      considered statistically significant. We observed significant diuretic,
      kaliuretic and natriuretic effects in the treated groups in a dose dependent
      manner. However, urinary pH remained unchanged during the course of the study.
      The diuretic index values showed good diuretic activity of the crude extract. The
      Lipschitz values demonstrated that the crude extract, at the dose of 50 mg/kg,
      showed 46% diuretic activity compared with furosemide. With regard to the acute
      toxicity study, no lethal effects were observed among Albino mice even at the
      higher dose of 5000 mg/kg. The extract of Nigella sativa, at the dose of 50
      mg/kg, significantly increased the urinary volume and modified the concentration
      of urinary electrolytes, and there was observed no signs of acute toxicity
      associated with the crude extract. Further studies are encouraged to isolate the
      pure phytochemical responsible for diuresis.

PMID- 25850209
TI  - Antioxidant and anti-inflammatory activity of Potentilla reptans L.
AB  - Potentilla species have been used in traditional medicine in the treatment of
      different ailment, disease or malady. Potentilla reptans (P. reptans) has been
      scarcely studied. The aim of this study was to test antioxidant and anti
      inflammatory activity of P. reptans aerial part and rhizome. DPPH assay was used
      to measure antioxidant activity of aqueous plant extracts. Anti-inflammatory
      effect was evaluated by experimental animal model of phenol-in-acetone induced
      mice ear edema. DPPH radical-scavenging activity of both tested extracts was
      concentration dependent with IC50 values 12.11 MUg/mL (aerial part) and 2.57
      MUg/mL (rhizome). Maximum anti-inflammatory effect (61.37%) was observed after
      administration of 10 mg/ear of the rhizome extract and it was 89.24% of effect
      induced by dexamethasone as a standard. In conclusion, P. reptans rhizome aqueous
      extract possesses anti-inflammatory effect and higher antioxidant activity than
      aerial part.

PMID- 25850210
TI  - In vitro and in vivo antimicrobial evaluation of alkaloidal extracts of Enantia
      chlorantha stem bark and their formulated ointments.
AB  - The in vitro and in vivo antimicrobial evaluation of the formulated ointment of
      alkaloidal extract of Enantia chlorantha Oliv. (Annonaceae) was the concern of
      this study. The alkaloidal fraction of the stem bark extract was formulated into
      simple ointment using British Pharmacopoeia formula for preparation of simple
      ointment. Agar diffusion and agar dilution methods were used for the in vitro
      antimicrobial studies. Ketoconazole 4000 MUg/mL and tioconazole cream 1% were
      used as reference standards while normal saline was used as control. The
      fungicidal activity kinetics of the plant extract was carried out using selected
      concentrations of the plant extract against the most sensitive organism (Candida
      albicans). For the in vivo studies, 25 albino rats weighing between 180-200 g
      were divided into 5 groups, anesthesized (thiopental sodium 50 mg/kg), infected
      with overnight culture of Candida albicans and incubated at 37 degrees C for
      three days to allow for growth of the microorganisms. Each of the five groups was
      treated on the third day of incubation with different concentrations of the
      formulated simple ointment (200 mg/mL, 100 mg/kg, 50 mg/mL), tioconazole cream 1%
      (reference standard) and normal saline control, respectively. The alkaloidal
      extract exhibited greater zones of inhibition with Candida glabrata and
      Trichophyton tonsurans while Candida albicans and Trichophyton interdigitali also
      showed some sensitivity. There was no surviving organism at the end of 240 min at
      100 mg/mL concentration with 10(-4) dilution factor. Treatment of the infected
      rats with the formulated simple ointments (200, 100 and 50 mg/mL) showed that 50
      mg/mL ointment had a better percentage reduction in the fungal loads at the end
      of the experiment when compared with the 200 mg/mL simple ointment as well as the
      standard tioconazole 1% cream and normal saline treated rats, respectively. The
      alkaloidal fraction of Enantia chlorantha stem bark as well as the formulated
      ointment exhibited significant in vitro and in vivo antifungal activities against
      different species of Candida, dermatophytes and plant fungi.

PMID- 25850211
TI  - Effects of white mulberry (Morus alba) leaf tea investigated in a type 2 diabetes
      model of rats.
AB  - The present study was aimed to investigate the anti-diabetic effects of a low
      (0.25%) and a high (0.5%) dose of white mulberry leaf tea in a rat model of type
      2 diabetes (T2D). Six week old male Sprague-Dawley rats were divided into four
      groups: Normal control (NC), Diabetic control (DBC), Diabetic mulberry tea low
      (DMTL, 0.25%) and Diabetic mulberry tea high (DMTH, 0.50%). T2D was induced by
      feeding a 10% fructose solution in drinking water for 2 weeks to induce insulin
      resistance, followed by a single injection (i.p.) of streptozotocin (40 mg/kg
      body weight (b.w.)) to induce partial pancreatic beta-cell dysfunction in all
      groups except the NC group, which only received a normal drinking water and
      citrate buffer (pH 4.4) instead of fructose solution and STZ injection,
      respectively. After 4 weeks feeding of brewed mulberry leaf tea, there were no
      significant improvements in polyphagia, polydipsia, body weight gain, blood
      glucose, glucose intolerance, serum insulin, fructosamine, AST, ALT, creatinine,
      albumin and uric acid levels and liver parameters when serum total cholesterol
      was significantly and LDL-cholesterol and triglyceride concentrations were
      markedly decreased in the DMTH group compared to the DBC and DMTL groups. Serum
      total proteins were significantly reduced in DMTL and DMTH groups compared to the
      DBC group. These results suggest that brewed white mulberry leaf tea has
      hypolipidemic rather than antidiabetic effects at least in this experimental
      condition. However, the effects of the different brands of white mulberry leaf
      tea may be varied due to various factors.

PMID- 25850212
TI  - The influence of low process temperature on the hydrodynamic radius of polyNIPAM
      co-PEG thermosensitive nanoparticles presumed as drug carriers for bioactive
      proteins.
AB  - The aim of the work was to evaluate the influence of low process temperature on
      the hydrodynamic radius of the synthesized nanoparticles presumed for
      incorporation of bioactive proteins. The reaction prompted in temperatures of 22,
      38 and 70 degrees C. The first one reflected the ambient environmental
      temperature, at which the bioactive proteins may be implemented into the reactant
      mixture. The intermediate temperature should enable safe use of proteins during
      the reaction, and represents the upper limit of applied heat, due to the
      consequent denaturation of proteins at elevated temperatures. The reactant
      mixture heated up to 70 degrees C provides excellent formation of nanoparticles,
      however the albuminous components will tend to degrade. Within the study we
      applied N,N,N',N'-tetramethylethane-1,2-diamine as an accelerator in the presence
      of the strong oxidizing agent--ammonium persulfate as radical initiator. Six
      batches of N-isopropylacrylamide derivatives with polyoxyethylene glycol
      diacrylamide co-monomer of molecular weight in the range of 2000 Da were
      synthesized within the course of surfactant free precipitation polymerization.
      The nanodispersions were assessed in the terms of hydrodynamic radius, by the
      dynamic light scattering method (DLS). The polydispersity index, as well as
      average hydrodynamic radius, and hydrodynamic radius of main population of
      particles, identified in the DLS device, were evaluated and discussed in the
      perspective of application of the nanogels as drug carriers for bioactive
      proteins.

PMID- 25850213
TI  - Fast ultra-fine self-nanoemulsifying drug delivery system for improving in vitro
      gastric dissolution of poor water soluble drug.
AB  - Meloxicam (MLX) has poor water solubility which leads to slow absorption
      following oral administration; hence, immediate release tablet is unsuitable in
      the treatment of acute pain. The aim of this study was to prepare a novel fast
      ultra-fine self-nanoemulsifying drug delivery system (UF-SNEDDS) of MLX for oral
      administration to facilitate drug release process in the stomach as well as
      comparing its in vitro dissolution with commercial Mobic and Mobitil tablets. MLX
      solubility in oils, mixed glycerides and surfactants with different HLB values
      was investigated. Based on MLX solubility profiles, eight UF-SNEDDSs composed of
      MLX, Cremophor RH 40 as oily phase, Capmul MCM-C8 or Tween 80 as surfactant and
      PEG 400 as co-solvent were prepared and evaluated for their spontaneous formation
      of emulsion, droplet size, turbidity and in vitro dissolution. The prepared novel
      MLX formulations showed a significant very low droplets size (up to 25 nm),
      thermodynamically stable and spontaneously formed nanoemulsion. MLX UF-SNEDDS
      formulations showed significant high percentage of drug dissolution (up to 70%)
      in simulated gastric fluid, compared with Mobic and Mobitil. In conclusion, due
      to higher drug release from MLX UF-SNEDDS formulations they could enhance its
      absorption and hence its bioavailability.

PMID- 25850214
TI  - Amorphous solid dispersion studies of camptothecin-cyclodextrin inclusion
      complexes in PEG 6000.
AB  - Abstract: The present work focused on the solubility enhancement of the poorly
      water-soluble anti-cancer agent camptothecin which, in its natural state,
      presents poor solubility inducing lack of activity with a marked toxicity. A new
      approach is adopted by using a ternary system including camptothecin (CPT) and
      cyclodextrins (CDs) dispersed in polyethylene glycol (PEG) 6000. Camptothecin
      solubility variations in the presence of alpha-CD, beta-CD, gamma-CD,
      hydroxypropyl-alpha-CD (HPalpha-CD), hydroxypropyl-beta-CD (HPbeta-CD), permethyl
      beta-CD (PMbeta-CD) and sulfobutyl ether-beta-CD (SBEbeta-CD), were evaluated by
      Higuchi solubility experiments. In the second part, the most efficient
      camptothecin/P-CDs binary systems, mainly HPbeta-CD and PMbeta-CD, were dispersed
      in PEG 6000. In addition to a drug release and modeling evaluation, the CPT
      interactions with CDs and PEG 6000 to prepared the amorphous solid dispersion in
      the binary and ternary systems were investigated by Fourier transformed infrared
      spectroscopy (FT-IR), differential scanning calorimetry (DSC), thermogravimetric
      analyses (TGA) and X-ray powder diffraction (XRPD). The results showed that
      HPbeta-CD and PMbeta-CD were the most efficient for camptothecin solubilization
      with highest apparent equilibrium constants. Dissolution studies showed that
      percentage of CPT alone after two hour in 0.1 M HCI medium, did not exceed 16%,
      whereas under the same conditions, CPT/PMbeta-CD complex reached 76%. When
      dispersing the binary systems CPT/beta-CDs in PEG 6000, the velocity and the
      percentage of CPT release were considerably improved whatever the CD used,
      reaching the same value of 85%. The binary and ternary systems characterization
      demonstrated that CPT inclused into the CDs cavity, replacing the water
      molecules. Furthermore, a drug transition from crystalline to amorphous form was
      obtained when solid dispersion is realized. The present work demonstrated that
      ternary complexes are promising systems for CPT encapsulation, and offer
      opportunities to use non toxic and commonly solubilizing carriers: betaCD and PEG
      6000 to improve bioavailability.

PMID- 25850215
TI  - Preparation and in vitro characterization of a non-effervescent floating drug
      delivery system for poorly soluble drug, glipizide.
AB  - The aim of the present study was to formulate a non-effervescent floating drug
      delivery system of glipizide, a poorly water soluble drug. The solubility of
      glipizide was initially enhanced using a solid dispersion (SD) strategy with the
      help of hydrophilic carriers such as poloxamer, cyclodextrin, and povidone. The
      optimized core material/SD was further formulated into non-effervescent floating
      tablets (NEFT) by using matrix ballooning inducers, such as crospovidone and
      release retarding agents including HPMC and PEO. Poloxamer-based solid
      dispersions prepared by a solvent evaporation technique showed the highest
      dissolution rate (1 : 10 drug to carrier ratio) compared with all other
      dispersions. NEFT were evaluated for all physico-chemical properties including in
      vitro buoyancy, dissolution, and release rate. All of the tablets were found to
      be within pharmacopoeial limits and all of the formulations exhibited good
      floating behavior. The formulations (F2 and F3) were optimized based on their 12
      h drug retardation with continuous buoyancy. The optimized formulations were
      characterized using FTIR and DSC and no drug and excipient interaction was found.
      In-vitro buoyancy and dissolution studies showed that non-effervescent floating
      drug delivery systems provide a promising method of achieving prolonged gastric
      retention time and improved bioavailability of glipizide.

PMID- 25850216
TI  - Effect of alloferon 1 on central nervous system in rats.
AB  - Alloferon 1 is an insect-derived peptide with potent antimicrobial and antitumor
      activity. It was isolated from blood of an experimentally infected insect, the
      blow fly Callifora vicina. Synthetic alloferon 1 reveals a capacity to stimulate
      activity of NK cells and synthesis IFN in animal and human models. Moreover, it
      was demonstrated antiviral and antitumor activity of alloferon 1 in mice. There
      are no data on influence of alloferon 1 on central nervous system. The aim of
      present study was to determine an effect of alloferon 1 on rats' central nervous
      system by some behavioral tests: open field test, hole test, score of rats
      irritability, and determination of memory consolidation in the water maze test.
      Moreover, a probable antinociceptive effect of alloferon 1 in rats was determined
      by a tail immersion test and hot plate test. Experiments were performed on female
      Wistar rats. Seven days before experiments, rats were anesthetized with ketamine
      and xylazine and polyethylene cannulas were implanted into the right lateral
      brain ventricle (i.c.v.). On the day of experiment, alloferon 1 dissolved in a
      volume of 5 MUL of saline was injected directly i.c.v. through implanted cannulas
      at doses of 5-100 nmol. It was found that alloferon 1 had slight effect on
      locomotor and exploratory activity, induced some decrease of rat irritability and
      a weak impairment of rats memory (only at the low dose of 5 nmol). On the other
      hand, the higher dose of this peptide exerts significant antinociceptive effect.
      Obtained results indicate that alloferon 1 do not exert any evidently toxic
      effect on central nervous system in rats. Therefore, alloferon 1 may be good new
      drug with antitumor and antinociceptive activity.

PMID- 25850217
TI  - Variation in vitamin D plasma levels according to study load of biomedical
      students.

PMID- 25850218
TI  - [Claude Leclerc, from theater to mental health].

PMID- 25850219
TI  - [Augustinian monastery. 375 years of nursing commitment].

PMID- 25850220
TI  - [Chaudiere-Appalaches. Prevent infections in the elderly residents].

PMID- 25850221
TI  - [Abitibi-Temiscamingue. Role of the nurse in isolated communities].

PMID- 25850222
TI  - [Mauricie/Central Quebec. Less waiting in hemato-oncology].

PMID- 25850223
TI  - [Advocacy for enhancement of clinical judgment. The Braden Scale: reactions].

PMID- 25850224
TI  - [The Braden Scale: reactions (cont.)].

PMID- 25850225
TI  - [PTI and DSQ].

PMID- 25850226
TI  - [Vicarious trauma or compassion fatigue, beware!].

PMID- 25850227
TI  - [Obstructive sleep apnea. A sleep disorder with serious consequences].

PMID- 25850228
TI  - [Parkinson's disease. A delicate balance].

PMID- 25850229
TI  - [Intensive care. The CPOT, assess pain of unconscious adult patients].

PMID- 25850230
TI  - [SIPPE. How to maintain the loyalty of the families to the program?].

PMID- 25850231
TI  - [Sterility breach in the operating room].

PMID- 25850232
TI  - [Vitamin D. Even more sunshine vitamin for overweight people].

PMID- 25850233
TI  - [Polymyalgia rheumatica. A higher risk of heart attack and stroke].

PMID- 25850234
TI  - [Partial epilepsy: Aptiom].

PMID- 25850236
TI  - [The digital polymerase chain reaction as a new technology and its potential
      input in molecular diagnostic].

PMID- 25850235
TI  - [The coding according molecular mass of synthetic biomarkers under comprehensive
      testing of urine components: horizons of disease monitoring].

PMID- 25850237
TI  - [MALDI-TOFF mass spectrometry: transformative proteomics in clinical
      microbiology].

PMID- 25850238
TI  - [The microprobes of antigens for studying of autoimmune diseases].

PMID- 25850239
TI  - [The evaluation of sensitivity and specificity of technique of detection of C
      reactive protein under diagnostic of infectious complications in patients with
      acute lymphoblastic leucosis receiving chemotherapy].
AB  - The C-reactive protein is a generally recognized marker of inflammation and
      bacterial infection. However, issue of diagnostic effectiveness of this indicator
      is still open-ended in case of patients with oncologic hematological diseases.
      The level of C-reactive protein can increase under neoplastic processes. On the
      contrary, the inhibition of immune response observed under cytoplastic therapy
      can decrease synthesis of this protein. The study was organized to establish
      levels of C-reactive protein as markers of infection in adult patients with acute
      lymphoblastic leucosis under application of chemotherapy and to evaluate their
      diagnostic effectiveness. The sampling included 34 patients with acute
      lymphoblastic leucosis all patients had infectious complications at various
      stages of treatment. The levels of C-reactive protein in groups of patients with
      localized infections (mucositis, abscess, pneumonia, etc.) or fever of unknown
      genesis had no statistical differences but were reliably higher in patients
      without infectious complications. The concentrations of C-reactive protein in
      patients with syndrome of systemic inflammatory response and sepsis had no
      differences. At the same time, level of C-reactive protein under systemic
      infection (syndrome of systemic inflammatory response, sepsis) was reliably
      higher than in case of localized infection. The diagnostically reliable levels of
      C-reactive protein were established as follows: lower than 11 mg/l--infectious
      complications are lacking; higher than 11 mg/l--availability of infectious
      process; higher than 82 mg/l--generalization of infection. The given levels are
      characterized by high diagnostic sensitivity (92% and 97% correspondingly) and
      specificity (97% and 97%) when patients receive therapy without application of L
      asparaginase. At the stages of introduction of this preparation effecting protein
      synthesizing function of liver sensitivity of proposed criteria are decreased
      (69% and 55% correspondingly). However; due to high specificity (100% and 96%)
      their diagnostic effectiveness remains high.

PMID- 25850240
TI  - [The application of eosin and propidium iodide in evaluation of vitality of human
      spermatozoa].
AB  - The article analyzes comparative assessment of vitality of spermatozoa by
      condition of permeability of membranes for eosin and propidium iodide and
      comparison of results acquired using technique of light and fluorescent
      microscopy. The comparison of data of light microscopy with eosin staining with
      data of fluorescent microscopy with propidium iodide staining demonstrated that
      percentage of content of spermatozoa separated from ejaculates of 28 fertile
      males and stained with eosin was reliably higher (34.8 +/- 3.2) than percentage
      of content of spermatozoa with stained with propidium iodide (2.1 +/- 4.0). After
      incubation of spermatozoa under room temperature during 24 hours percentage of
      unviable cells with stained eosin also was higher than in case of propidium
      iodide staining correspondingly (44.5 +/- 3.3% and 34.7 +/- 3.6%). The analysis
      of vitality of spermatozoa under damaging effect of oxidative stress on cell
      membrane developed by 4 hours incubation with 200 mkM of hydrogen peroxide (H2O2)
      demonstrated that under staining of spermatozoa with propidium iodide
      significantly higher percentage of damaged cells is detected. In such cases,
      eosin staining is less suitable for detection of vitality of spermatozoa (73.6 +/
      5.8% against 51.7 +/- 6.4%). The carried out experiment demonstrates that in
      case of detected effects on spermatozoa (for example, effect of oxidative stress)
      the light microscopy insufficiently adequate reflects degree of damage of
      membranes of spermatozoa. The fluorescent microscopy detects a higher percentage
      of spermatozoa with damaged membrane.

PMID- 25850241
TI  - [The prognostic value of evaluation of minimal residual disease using technique
      of flow cytofluorometry during application of therapy of chronic lymphatic
      leukemia].
AB  - The achievement of molecular remission is associated with increasing of survival
      of patients with chronic lymphatic leukemia. The important direction of research
      is seeking of parameters applicable to forecast of response to therapy. The
      purpose of the study was evaluating prognostic significance of indicator of
      minimal residual disease detected by technique of flow cytofluorometry of
      peripheral blood of patients with chronic lymphatic leukemia during therapy
      application. The sampling included 112 patients with chronic lymphatic leukemia
      aged from 43 to 82 years. All patients were given treatment consisted of 6
      courses of immune chemotherapy combined with fludarabine with cyclophosphan and
      rituximab. The samples of peripheral blood were analyzed after 3 courses during
      therapy and after 6 courses after completion of treatment. The cells were
      analyzed using 5 and 6 color flow cytometry for the purpose of detection of
      immune phenotype associated with chronic lymphatic leukemia. The evaluation of
      minimal residual disease was implemented according international standardized
      protocol (Rawstron A.C. et al. 2007; 21 (5): 956-64). The minimal residual
      disease negative status was reached in 87 (78%) patients during evaluation of
      response after 6th course of treatment. The implementation of indicators of
      residual disease after 3 courses with fludarabine, cyclophosphan and rituximab
      permitted to sort out two groups of patients with chronic lymphatic leukemia i.e
      67 patients with low (< 0.12%) level of minimal residual disease and 45 patients
      with high (> 0.12%) level of tumor cells. The rate of molecular remission after
      completion of treatment. in the given groups consisted 100% and 44%
      correspondingly. The study demonstrates possibilities of early immune phenotype
      evaluation of minimal residual disease to forecast differences in response to
      treatment in patients with chronic lymphatic leukemia that makes it possible to
      avoid undesirable toxicity of therapy or to choose method of consolidation.

PMID- 25850242
TI  - [The cytological diagnostic of adenocarcinoma of pancreas with technique of size
      separation of tumor cells circulating in peripheral blood (case report)].
AB  - The diagnostic of tumor cells circulating in blood is one of most perspective and
      actively developing directions in cytology. The most of proposed techniques for
      this purpose are based on using immune cytochemical or molecular genetic modes to
      characterize cells. At the samne time, growing spread receives technique of
      separation of circulating tumor cells based on their larger size in comparison
      with other blood cells (ISET). The article presents clinical monitoring of
      application of mentioned technique to verify diagnosis and onset of treatment in
      female patient with reiterated ineffective diagnostic punctures of pancreas.

PMID- 25850243
TI  - [The effect of prolonged flow aspiration drainage of laparotomy wounds of
      oncological coloproctologic patients on cytological parameters of wound
      secretion].
AB  - In oncologic coloproctologic patients the comparative cytological analysis of
      wound secretion in healing midline laparotomy wounds was implemented. The wounds
      were taken in common way (layer-by-layer tightly) and with prolonged flow
      aspiration drainage of subcutaneous cellular tissue. It is proved that
      application of prolonged flow aspiration drainage effects positively on
      regeneration process and objectively reflects more benevolent course of healing
      of laparotomy wounds. In the end, this mode decreases number of festering from
      7.3% in control group to 1.6% in main group (p < 0.05).

PMID- 25850244
TI  - [The count of urine corpuscles using automated analyzer Iris IQ 200 TM].
AB  - The volume of urine of high power field of analyzer Iris IQ 200 TM was identified
      according standard of stabilizing erythrocytes and amounted up to 0.18 mkl. The
      amount of urine corpuscles detected by analyzer in this volume corresponds to
      amount of urine corpuscles under microscopy of sediment often times concentrated
      urine at thickness of preparation in 0.1 mm, under microscope with objective x40
      and ocular 10/18. The count of corpuscles by analyzer in 1 mkl of urine is the
      most objective and convenient technique for quantitative evaluation of urine
      corpuscles.

PMID- 25850245
TI  - [The diagnostic of defects of inborn immunity under B-cell tumors of lymphatic
      system].
AB  - The genetic characteristics are key risk factors of development of many human
      neoplasms including B-cell tumors of lymphatic system. The relationship between
      polymorphic variants of genes FCGR2A (His 1 66Agr), CD14 (C-159T). IL1beta (T
      31C), IL2 (7:330G) and 7LR2 (Arg753Ghn) and development of various forms of B
      cell tumors of lymphatic system in 80 patients was investigated. The
      statistically significant differences of rates of particiular genotypes of single
      nucleotid polymorphisms of genes FCGR2A, CD14. IL1beta, IL2 and TLR2 in patients
      with indolent and aggressive types of course of non-Hodgkin lymphoma and also
      multiple myeloma. The results prove hypothesis that genetic variants of genes of
      inborn immune response effect the origin and character of course of different
      types of lymphoproliferative diseases. The markers can become additional
      prognostic characteristics of benign and aggressive course of tumors.

PMID- 25850246
TI  - [The antibodies to neurohormonal anti-genes as a criterion of early diagnostic
      and neurointoxication in workers of chemical enterprises].
AB  - The examination was applied to enterprise workers laboring in conditions of vinyl
      chloride (79 patients), caustic soda (24 patients) and 10 patients with
      professional chronic mercury intoxication. The differences are established
      concerning manifestation of autoimmune reactions of personnel working in
      conditions of chronic effecting of vinyl chloride distinct of parameters
      characterizing autoimmune reactions of personnel working under impact of another
      neuro-toxicants (vapors of metallic mercury). The increasing of auto-antibodies
      to MAG was detected in healthy personnel and increasing of concentrations of auto
      antibodies to protein S-100 and DNA was detected in personnel with initial
      manifestations of neuro-intoxication. These occurrences testify availability, of
      different mechanisms underlying formation of neurological disorders. The study
      data confirms involvement of auto-antibodies to neuronal antigens into
      derangement of neural activity in personnel working in conditions of effect of
      vinyl chloride and vapors of metallic mercury. Hence, the new possibilities are
      opened in studying pathogenesis of occupational neuro-intoxications. The
      detection of auto-antibodies to proteins of neural tissue can be recommended as a
      criterion of early identification of damage of neural system in personnel working
      in conditions of chemical industry.

PMID- 25850247
TI  - [The prognostic significance of particular immunological indicators of lachrymal
      fluid in patients using soft contact lenses].
AB  - The study was carried out to identify concentrations of vessel epithelium growth
      factor (VEGF), souble forms of VEGF receptor type I and II, chemo-toxic protein I
      and metalloproteinase-9 in lachrymal fluid. The immune enzyme analysis was
      applied. He sampling included patients with myopia without complications while
      using silicone hydro-helium and hydro-helium contact lenses and patients with
      hypoxic complications of contact correction. It is established that application
      of hydro-helium and silicone hydro-helium contact lenses more than one year is
      followed by increasing of concentration of detected substances in lachrymal
      fluid. Under hypoxic complications of contact correction the levels of substances
      are significantly higher than in cases without complications. This occurrence
      makes it possible to substantiate possibility of application of immunologic
      indicators as diagnostic markers.

PMID- 25850248
TI  - [The separation, identification and molecular biologic analysis of isolates of
      pandemic influenza virus A(H1N1)pdm09].
AB  - The article presents data concerning analysis of bioassays under suspicion of
      influenza A(H1N1)pdm09. The technique of back transcription polymerase chain
      reaction and sequencing was applied. The separation of native influenza virus A
      was implemented using passaging through developing chick embryos.

PMID- 25850249
TI  - [The formation of bio-films by opportunistic microorganisms isolated from
      patients with rheumatic diseases].
AB  - The study was carried out concerning capability of 194 strains of opportunistic
      microorganisms to form bio-films. It is established that bacteria ecizing
      organism of patients with rheumatic diseases have capacity to form microbial bio
      films. The formation of bio-films is manifested with the same rate as in agents
      of inflammatory processes. At that, Escherichia coli, Staphylococcus haemolyticus
      and bacteria of genus Proteus isolated under rheumatic diseases have
      significantly higher capability to form biofilms that matters for development of
      comorbide infections.

PMID- 25850250
TI  - [The detection of strains of Esherichia coll producing Shiga toxin in populations
      of normal intestinal microbiota in children with functional disorders of
      gastrointestinal tract].
AB  - In intestinal ecosystem, interchange of genetic material between different types
      of bacteria and other representatives of family Enterobacteriaceae results in
      development of types of normal colibacillus with genetic characteristics of
      pathogenicity. This occurrence can be considered as a theoretical substantiation
      for labeling such strains as pathobionts. The polymerase chain reaction was
      implemented to analyze 96 strains of different types of Escherichia coli (with
      normal and weak zymogenic activity and hemolytic activity) isolated from children
      with functional disorders of gastrointestinal tract. The purpose was to detect
      presence of gens coding capacity of toxin production (six1, stx2). In intestinal
      biotope of children, circulation of strains of Escherichia coli producing shiga
      toxin having no relation to pathogenic group being representatives of normal
      indigenous microbiota. The presence of gens stx1 and stx2 in various biochemical
      types of Escherichia coli permits establishing fact of forming of reservoir of
      potential pathogenicity in non-pathogenic forms of Escherichia coli. The presence
      of gen (verotoxin 1) in genome of various types of Escherichia coli isolated from
      one single biotope testifies possible horizontal transmission of factors of
      pathogenicity in intestinal biotope.

PMID- 25850252
TI  - [Community characters of Lophatherum gracile in Yongchuan district of Chongqing].
AB  - To understand Lophatherum gracile plant community's structural characteristics, a
      survey of community structure and species diversity was conducted through quadrat
      sampling in Yongchuan district of Chongqing. The results showed that there were
      386 species vascular plants, belonging to 117 families and 229 genera. Based on
      habitat, community structure and species composition, L. gracile were found in
      three community types: Pinus massoniana community, banboo community, shurb
      community. Vertical structure was composed of three layers, including tree layer,
      shrub layer and herb layer. Species in shrub layer was the richness. P.
      massoniana is the only dominant species of the community, it can not regenerate
      naturally, the shrub layer has a greater effect on the community of L. gracile in
      the future. In addition, the banboo community and shurb community is not stable
      because of human's activity. Therefore, the community characters of L. gracile
      should be taken care of conservation when the resources are utilized.

PMID- 25850251
TI  - [The quantitative testing of V617F mutation in gen JAK2 using pyrosequencing
      technique].
AB  - The somatic mutation V617F in gen JAK2 is a frequent cause of chronic
      myeloprolific diseases not conditioned by BCR/ABL mutation. The quantitative
      testing of relative percentage of mutant allele can be used in establishing
      severity of disease and its prognosis and in prescription of remedy inhibiting
      activity of JAK2. To quantitatively test mutation the pyrosequencing technique
      was applied. The developed technique permits detecting and quantitatively,
      testing percentage of mutation fraction since 7%. The "gray zone" is presented by
      samples with percentage of mutant allele from 4% to 7%. The dependence of
      expected percentage of mutant fraction in analyzed sample from observed value of
      signal is described by equation of line with regression coefficients y = - 0.97,
      x = -1.32 and at that measurement uncertainty consists +/- 0.7. The developed
      technique is approved officially on clinical material from 192 patients with main
      forms of myeloprolific diseases not conditioned by BCR/ABL mutation. It was
      detected 64 samples with mautant fraction percentage from 13% to 91%. The
      developed technique permits implementing monitoring of therapy of myeloprolific
      diseases and facilitates to optimize tactics of treatment.

PMID- 25850253
TI  - [Effect of total ginsenosides on protective enzymes of Mythimna separata larvae].
AB  - Under indoors simulating natural growing condition, the 4th-instar Mythimna
      separata larvae were fed by using poi- son leaf disk method. The effect of total
      ginsenosides on the protective enzymes (PPO, T-SOD, CAT and POD) of M. separata
      larvae was studied. The total ginsenosides could influence the protective enzymes
      of 4th-instar M. separata larvae significantly. After treated by total
      ginsenosides, the PPO activities increased firstly then decreased, and tended to
      equilibrium, and reached the maximum after 48 h. Furthermore, the total
      ginsenosides disturbed the dynamic balance of SOD, CAT and POD of M. separata
      larvae, and the yield of O2-* speeded. The results suggest that the total
      ginsenosides influence the protective enzymes of 4th-instar M. separata larvae,
      and disturb the original dynamic balance of protective enzymes. Consequently the
      insect suffers from the harm of O2-*.

PMID- 25850254
TI  - [Isolation of endophytic fungi from Macleaya cordata and screening of
      sanguinarine-producing strains].
AB  - Endophytic fungi were isolated from Macleaya cordata growing in Dabie Mountain by
      agar-block method, and then the endophytic fungi were grouped into different
      types based on their morphological characteristics, and thin layer chromatography
      (TLC) and high performance liquid chromatography (HPLC) were employed to
      determine whether the metabolic substances contained sanguinarine or not, and
      then preliminarily identified by morphological method. The results showed that
      the leaves hosted the largest number of endophytes (96 isolates) followed by the
      stems (57 isolates) and finally the roots (28 isolates), respectively. Based on
      morphological characteristics the endophytic fungi were grouped into 26 types in
      our study. TLC and HPLC results showed that there was sanguinarine in the
      metabolic substances of BLH 51 strain. According to the morphological
      characteristic, the BLH 51 strain was identified as Fusarium proliferatum. All
      these indicated that the medicinal plant M. cordata harbors abundant endophytes,
      which could be a new source for the search of active secondary metabolites.

PMID- 25850255
TI  - [Study on preferred food of adult Mylabris phalerata in different geographical
      populations].
AB  - With the deterioration of environment, and the excessive collection of wild
      resources, the wild populations of Myla- bris phalerata Pallas are less and less,
      almost extincted in many traditional distribution areas. It is necessary to breed
      M. phalerata artificially for sustainable utilization. Food preference of adult
      M. phalerata is the key to its provenance screening and domestication in the
      artificial breeding. In this paper, the food preference of 3 geographical
      populations of M. phalerata was studied. The results showed that the food
      preferences of adult M. phalerata in different geographical populations were
      different. The adult M. phalerata in Wuming preferred cucumber flowers, gourd
      flowers and melon flowers. The adult M. phalerata in Tianlin preferred cowpea
      flowers. And the adult M. phalerata in Guangzhou preferred cowpea flowers and
      gourd flowers. Gourd flowers were the most attractive food for the adult M.
      phalerata of 3 geographical populations of M. phalerata.

PMID- 25850256
TI  - [Effect of combined application of zinc, boron and molybdenum on yield and
      saikosaponin a, saikosaponin d contents of Bupleurum chinense].
AB  - This research use "3414" fertilizer effect experiments to handle zinc, boron and
      molybdenum trace element fertilizer, determined the dry matter accumulation and
      content of saikosaponion a and d, to investigate the different ratio of zinc,
      boron and molybdenum on yield and saikosaponin a, saikosaponin d contents of
      Bupleurum chinense. Found The suitable ratio of zinc, boron and molybdenum play
      an active role on dry matter accumulation and distribution, the treatment
      Zn2B2Mo3 is the best one to promote the dry matter accumulation and transfer to
      the underground part; in a certain range, only use zinc or molybdenum can promote
      the yield of B. chinense, the yield of treatment Zn2B2Mo1 is the highest one.
      According to the results of regression analysis: in accordance with Zn 48.45 g x
      hm(-2), B 355.05 g x hm(-2), Mo 86.40 g x hm(-2), can obtain the yield with
      3313.05 kg x hm(-2); the treatment Zn2BMo2 is most effective to promote the total
      saikosaponin a and d accumulated, according to the results of regression
      analysis: in accordance with Zn 36.15 g x hm(-2), B 343.05 g x hm(-2), Mo 106.35
      g x hm(-2), the content of total saikosaponin a and d can reach 1.23%. This
      research first discovered the suitable ratio of zinc, boron and molybdenum can
      promote the yield and saikosaponin a, saikosaponin d contents on B. chinense.

PMID- 25850257
TI  - [Differences of fungal diversity and structure in rhizosphere of Fritillaria
      thunbergii from different provenances].
AB  - To explore the mechanism of soil microbial ecology, the differences of fungal
      diversities in rhizosphere of different provenances of Fritillaria thunbergii
      were analyzed. The diversities and compositions of rhizo-fungi of the samples
      were analyzed by using DGGE and 454 pyrosequencing. DGGE results showed the
      Shannon index of Ninbo provenance planted in Ninbo was the highest one. And its
      dominant fungi were Ascomycota, Deuteromycota and Zygomycota. Except the same
      fungi, every provenance planted in Ninbo had its own special ones. From the 454
      pyrosequencing, the fungal diversity in Panan producing was the highest which was
      similar with DGGE result. Among the ten phylum detected in its rhizosoil,
      Fungi_incertae_sedis, Ascomycota, Mucoromycotina, Basidiomycota and
      Chytridiomycota almost amounted to 90% of the whole community. The fungal types
      and amounts in Panan were more than those in Ninbo indicating the differences
      between producing areas and the advantage of macro genome sequencing. There were
      10 phyla, 29 families, 28 genus and 159 species of fungi in Panan provenance, 6
      phyla, 20 families, 19 genus, 136 species in Ninbo provenance, 8 phyla, 37
      families, 47 genus, 289 species in Nantong provenance and 7 phyla, 25 families,
      24 genus, 102 species in the bulk soil. Some genus such as Dothidea,
      Capnobotryella and Conidiobolus were only existed in Nantong provenance, while
      Pyrenochae- ta, Glomus and Pseudonectria were only in Panan provenance, which
      implied these species could grew because F. thunbergii influenced the existence
      of fungi. Experiments of provenance and producing area of F. thunbergii showed
      that the fungal diversity of indigenous provenance was higher than that of exotic
      provenance and each provenance had unique fungal species in the rhizosphere,
      which indicated that the diversity and structure was shaped cooperatively by the
      species and soil type. These fungal species are interacted with the soil
      rhizhosphere-microbe microecological system, which in turn influence the growth
      of F. thunbergii.

PMID- 25850258
TI  - [Research on life history and phenological period of wild-stimulated cultivated
      Gastrodia elata f. elata in Guizhou].
AB  - In order to get to know the imitation of wild Gastrodia elata in life history and
      phenology period, by G. elata f. elata forest wild simulated cultivation in
      Dafang county, Guizhou province, observing and recording its morphological
      characteristics of each growth and development stage. This experiment summarized
      the law of its life history over 24 months, amplified the characteristics of each
      5 phenology periods over the sexual and asexual reproduction of wild simulated
      cultivated G. elata f. elata in Guizhou. Which the results could clear the
      process of wild simulated cultivated G. elata f. elata in Guizhou, and provide a
      theoretical support for the standard technical of the simulated wild G. elata.

PMID- 25850259
TI  - [Correlations between micromeritic properties of mixing powders of danshen
      extract and formability of their pellets].
AB  - It was difficult to prepare traditional Chinese medicine pellets due to the
      adverse characteristics of the herbal extract. In this study, Danshen extract
      (DS) powder mixed with different proportions of microcrystalline cellulose (MCC),
      lactose and starch were made into pellets by extrusion-spheronization. Particle
      size, span, bulk density, tapping density, compressibility, Hausner ratio and
      angle of repose were used to evaluate the micromeritic properties of mixing
      powders. Feret diameter, aspect ratio, yield, density and friability were used to
      evaluate the properties of the pellets. The correlations between micromeritic
      properties of raw material powders and the formability of their pellets were
      analyzed by cluster analysis, principal component analysis and partial least
      squares regression analysis. As a result, the particle size of the powders was
      negatively correlated with the size, density, yield, and was positively
      correlated with the friability of their pellets. The span, density,
      compressibility and angle of repose of the powders were positively correlated
      with the size, density, yield, and were negatively correlated with the friability
      of their pellets. So there were certain correlations between the micromeritic
      properties of raw material powders and the properties of their pellets prepared
      by extrusion-spheronization. This research provided a foundation for the
      technology and method of traditional Chinese medicine extract pellets.

PMID- 25850260
TI  - [Research on stability of melittin in different solvent systems].
AB  - The stability of melittin in different solvents (water, deoxygenated water,
      physiological saline, PBS, 50% ethanol, ethanol, glycerol)was studied and the
      results showed that the stability of melittin is not influenced by light,
      temperature and pH in 50% ethanol, which melittin can be completed dissolved when
      compared with ethanol and glycerol, in such, 50% ethanol was chosen as solvent
      storage when measured content of melittin. Then the effect of different
      concentrations of PBS, the pH of PBS and rat skin ho- mogenates were tested, and
      the results showed that melittin was degraded rapidly at low concentration
      solution and low ionic strength. Increasing pH of PBS and rat skin homogenate can
      accelerate the degradation of melittin. These researches provide an experimental
      ba- sis for further study of melittin.

PMID- 25850261
TI  - [Studies on new co-processed excipient consisting of lactose and gelatinized
      starch].
AB  - Co-processed excipients withgelatinized or non-gelatinized starch were prepared
      by spray drying. Powder and tablet properties of corocessed excipients prepared
      were compared with those of physical mixtures and spray-dried lactose. Their
      applicability in traditional Chinese medicine (TCM) powder tableting was tested
      on two TCM extracts, i.e., the gardenia extract and the Herba Sedi extract. It
      was shown that gelatinizing starch before co-spray drying with lactose could
      improve the performance and efficiency of starch as a binder, resulting in
      remarkable improvement in physicomechanical properties of co-processed excipients
      prepared. Conpared to self-made and commercially available spray-dried lactose,
      co-processed excipients achieved better compactability and higher drug loading
      for TCM extracts. In conclusion, the lactose-gelatinized starch co-processed
      excipient, with excellent physicomechanical properties, is promising to be
      explored as a new excipient for direct tableting.

PMID- 25850262
TI  - [Selecting solvent and solubilizer for puerarin nasal drops by solubility and
      irritation].
AB  - In order to test the equilibrium solubility of puerarin in different solvents and
      solubilizer,cilia toxicity and irritation of these excipient, the balance method,
      toad in the ciliary body toxicity and rat nasal mucosa irritation were used
      respectively. Results showed that puerarin solubility was 56.44 g x L(-1) in
      combined solvent of 30% PEG200 and 10% Kolliphor HS 15. With normal saline
      solution as negative control and sodium deoxycholate as positive control, the
      effects of 30% PEG200, 30% PEG 400, 10% Kolliphor HS 15 and combination of 30% of
      PEG200 and 10% Kolliphor HS 15 on toad palate cilium were observed and cilia
      movement duration was recorded. The results indicated that there was no
      significant difference in cilia movement duration among 30% PEG200, 10% Kolliphor
      HS 15 and normal saline group. The rats long-term nasal mucous membrane
      irritation of 30% PEG 400, 10% Kolliphor HS 15, which had no cilia toxicity, was
      studied, with normal saline solution as negative control. There were no
      significant difference revealed on rat nasal mucosa epithelial thickness among
      30% PEG 400, 10% Kolliphor HS 15 and normal saline. Above researches showed 30%
      PEG 400, 10% Kolliphor HS 15 was ideal for solubility of puerarin nasal drops and
      showed a lower cilia toxicity and irritation, and can be used as the solvent and
      solubilizer of puerarin nasal drops.

PMID- 25850263
TI  - [Study on absorbing volatile oil with mesoporous carbon].
AB  - Clove oil and turmeric oil were absorbed by mesoporous carbon. The absorption
      ratio of mesoporous carbon to volatile oil was optimized with the eugenol yield
      and curcumol yield as criteria Curing powder was characterized by scanning
      electron microscopy (SEM) and differential scanning calorietry (DSC). The effects
      of mesoporous carbon on dissolution in vitro and thermal stability of active
      components were studied. They reached high adsorption rate when the absorption
      ratio of mesoporous carbon to volatile oil was 1:1. When volatile oil was
      absorbed, dissolution rate of active components had a little improvement and
      their thermal stability improved after volatile oil was absorbed by the loss rate
      decreasing more than 50%. Absorbing herbal volatile oil with mesoporous carbon
      deserves further studying.

PMID- 25850264
TI  - [Chemical mechanisms involved in slow fire processing and pulverization of
      Brassica juncea].
AB  - This article dealed with the effects of processing method and duration on the
      major bioactive components (sinigrin and sinapine thiocyanate) in Brassica
      juncea. The contents of sinigrin and sinapine thiocyanate in decoctions of raw
      and processed B. juncea were determined and compared by high performance liquid
      chromatography on a Alltima C18 column (4.6 mm x 250 mm, 5 microm) at 35 degrees
      C with the acetonitrile-0.1% phosphoric acid as the mobile phrase in gradient
      elution. The detection wavelength of sinigrin and sinapine thiocyanate was set at
      227 nm and 326 nm, and the flow rate was 1.0 mL x min(-1). It was found that with
      the extended processing duration, the contents of sinigrin and sinapine
      thiocyanate first increased and then decreased: i.e., 0-2 minutes they increased
      gradually (for sinigrin, by 9.65% in processed products and 356. 10% in powder;
      for sinapine thiocyanate, by 12.82% in processed products and 3.41% in powder),
      and achieved their highest content at 2 min; then, decreased during the next 5
      minutes (for sinigrin, by 80.35% in processed products and 82.09% in powder; for
      sinapine thiocyanate, by 14.29% in processed products and 17.54% in powder),
      suggesting that processing duration could significantly affect the contents of
      bioactive components in B. juncea, enzymatic hydrolysis of sinigrin when the seed
      is crushed in the present of moisture may be responsible for the content change.
      It is recommended that the slow fire should be the best processing method and the
      raw seed could be used directly in the water extracts related industrial
      production.

PMID- 25850265
TI  - [Study on content variation of gallic acid and ellagic acid in course of
      processing of charred Granati Pericarpium].
AB  - The method for determining the content of gallic acid and ellagic acid in Granati
      Pericarpium was established by HPLC. Using the method, the content of raw and
      charred Granati Pericarpium was determined. By comparison, it was found that the
      content of gallic acid and ellagic acid increased first and then reduced during
      processing. When processed on an appropriate degree, the content reached the
      maximum. The result indicated that gallic acid and ellagic acid can be used as
      indicators to control the processing degree of charred Granati Pericarpium.

PMID- 25850266
TI  - [Investigation on chemical constituents of processed products of Eucommiae
      Cortex].
AB  - According to the 2010 Chinese pharmacopeia, salt processed and charcoal processed
      Eucommiae Cortex were pre- pared. HPLC-DAD analysis of the content of the bark
      and leaf of Eucommiae Cortex showed that the bark of Eucommiae Cortex mainly
      contained lignans such as pinoresinol glucose and iridoid including genipin,
      geniposide, geniposidic acid, while the leaf of Eucommiae Cortex consisted of
      flavonoids such as quercetin and phenolic compound such as chlorogenic acid. The
      content of pinoresinol diglucoside in the bark of Eucommiae Cortex was about 18
      times more than that in the leaf of Eucommiae Cortex. The content of pinoresinol
      diglucoside in salted and charcoal processed Eucommiae Cortex decreased
      approximately by 30% and 85%, respectively. The content of genipin, geniposide
      and geniposidic acid in the bark of Eucommiae Cortex was about 3 times, 23 times,
      28 times more than that in the leaf of Eucommiae Cortex. The content of genipin,
      geniposide and geniposidic acid in salted Eucommiae Cortex were reduced by 25%,
      40% and 40%, respectively. The content of genipin, geniposide and geniposidic
      acid in charcoal processed Eucommiae Cortex were reduced by 98%, 70%, 70%,
      respectively. The content of caffeic acid in bark of Eucommiae Cortex was about 3
      times more than that in the leaf of Eucommiae Cortex. The content of caffeic acid
      was decreased by about 50% in the salted Eucommiae Cortex. While the content of
      caffeic acid in charcoal processed Eucommiae Cortex was decreased approximately
      75%; the content of chlorogenic acid in bark of Eucommiae Cortex was about 1/6 of
      that in the leaf of Eucommiae Cortex. The content of chlorogenic acid in salted
      and charcoal processed Eucommiae Cortex decreased by 40% and 75%, respectively;
      the content of quercetin in bark of Eucommiae Cortex was only 1/40 of that in the
      leaf of Eucommiae Cortex. The content of quercetin in salted and charcoal
      processed Eucommiae Cortex were reduced by 60% and 50%, respectively.

PMID- 25850267
TI  - [Coumarins from Leonurus japonicus and their anti-platelet aggregative activity].
AB  - Chemical constituents of Leonurus japonicus were isolated and purified by a
      combination of various chromatographic techniques including column chromatography
      over silica gel, Sephadex LH-20, MCI, and Rp C18. Structures of the isolates were
      determined by spectroscopic analysis as 10 coumarins: bergapten (1), xanthotoxin
      (2), isopimpinellin (3), isogosferal (4), imperatorin (5), meransin hydrate(6),
      isomeranzin(7), murrayone(8) , auraptenol(9), and osthol(10). In addition to
      compound 9, the others were isolated from the genus Leonurus for the first time.
      In the in vitro assay, compounds 4 and 8 significantly inhibited the abnormal
      increase of platelet aggregation induced by ADP.

PMID- 25850268
TI  - [Studies on flavonoids from stems of Nelumbo nucifera Gaertn and their cytotoxic
      activities].
AB  - This research is to investigate study the flavonoids from stems of Nelumbo
      nucifera and the cytotoxic activities of iso- lated compounds. The constituents
      were separated by column chromatography,and their structures were elucidated by
      spectroscopic data analyses. The isolated compounds were evaluated for cytoxic
      activities by MTT method. Twelve compounds were isolated and identified as
      rhamnazin-3-O-beta-D-glucopyranoside (1), luteolin-3', 4'-dimethylether-7-O-beta
      D-glucoside (2), kaempferol-3-O-beta-D-xylopyranosyl-(1-->2)-O-beta-D
      glucopyranoside (3), quercetin-3,3'-di-O-beta-D-glucopyranoside (4), 1, 8
      dihydroxy-3,7-dimethoxyxanthone (5), isorhamnetin-3-O-beta-D-glucopyranoside(6) ,
      kaempferol(7), isorhamnetin (8), quercetin(9), astragalin(10), hyperoside (11)
      and 1-hy- droxy-3,7,8-trimethoxyxanthone(12). All compounds were isolated from
      stems of this plant for the first time, and compounds 1-5 were firstly isolated
      from the family nelumbonaceae. Compounds 24 and 6 showed significant cytotoxic
      activities against BEL-7402 carcinoma cell lines at a concentration of 1 x 10(-5)
      mol x L(-1) with the inhibitory rate of 67.36%, 53.25%, 57.78%, 60.13% and
      52.11%, respectively.

PMID- 25850269
TI  - [Qualitative and quantitative analysis of major constituents in Tetrastigma
      hemsleyanum by HPLC-Q-TOF-MS and UPLC-QqQ-MS].
AB  - A qualitative analytical method of liquid chromatography coupled with quadrupole
      time-of-flight tandem mass spectrometry (HPLC-Q-TOF-MS) was developed for
      identification of multi-constituents and an analytical method was developed for
      simultaneously determining 4 major compounds (rutin, isoquercitrin, kaempferol-3
      0-rutinoside, and astragalin) in Tetrastigma hemsleyanum Diels et Gilg. The HPLC
      Q-TOF-MS assay was performed on a Welch Ultimate XB-C18 column (4.6 mm x 150 mm,
      5 microm) with the mobile phase consisting of acetonitrile (A) and water
      containing 0.1% Formic acid (B) in gradient mode at a flow rate of 0.8 mL x min(
      1). The column temperature was at 30 degrees C, and negative ion mode was used
      for TOF-MS. The UPLC-QqQ-MS assay was performed on a Waters CORTECS C18 (2.1 mm x
      100 mm, 1.6 microm) with the mobile phase consisting of acetonitrile (A) and
      water containing 0.1% formic acid (B) in gradient mode at a flow rate of 0.25 mL
      x min(-1). The column temperature was at 45 degrees C, and MRM mode was used for
      QqQ-MS. Based on the retention time and MS spectra, 24 compounds were identified
      or tentatively characterized by comparing with reference substances or
      literatures. For quantitative the linear range of 4 detected compounds were good
      (r > 0.9966), and the overall recoveries ranged from 98.27% to 101.58%, with the
      RSD ranging from 3.15% to 5.88%. The results indicated that new approach conbined
      HPLC-Q-TOF-MS and UPLC-QqQ-MS was applicable in qualitative and quantitative
      quality control of Tetrastigma hemsleyanum.

PMID- 25850270
TI  - [Simultaneous determination of seven constituents in Lamiophlomis rotata by
      HPLC].
AB  - OBJECTIVE: To establish a new method for simultaneous determination of
      shanzhiside methyl ester, chlorogenic acid, 8-O-acetyl shanzhiside methylester,
      forsythiaside B, rutin, acteoside and galuteolin in Lamiophlomis rotata. METHOD:
      Separation was performed on a Welchrom-C18 chromatographic column with
      acetonitrile-0.1% orthophosphoric acid as mobile phasewith gradient elution. The
      flow rate was 1.0 mL x min(-1). The column temperature was 30 degrees C, and the
      detection wavelength was set at 238 nm, 330 nm and 350 nm. RESULT: The seven
      compounds were well separated with good linear correlations. The mean recoveries
      of seven compounds were 96.47%-102.2% (RSD 0.70%-2.2%). CONCLUSION: There were
      good correlations among the seven compounds in the samples of aerial parts. The
      mean sum of shanzhiside methyl ester and 8-O-acetyl shanzhiside methylester in
      samples of aerial parts is 1.44%. The aerial parts have more kinds of composition
      and with higher content than that of underground parts in L. rotata, which was
      reasonable for the resonable use of the aerial part as medicinal part. The method
      was simple, repeatable and stable, which could be used for identification and
      quality evaluation of L. rotata.

PMID- 25850271
TI  - [Determination of five triterpenic acids from Salvia chinensis of different parts
      by RP-HPLC-PDA].
AB  - OBJECTIVE: To establish a RP-HPLC-PDA method for determination of five
      triterpenic acids (pomolic acid, hawthorn acid, corosolic acid, oleanolic acid
      and ursolic acid) in different parts of Salvia chinensis. METHOD: The isocratic
      elution and separation was achieved on a Kromasil C18 column (4.6 mm x 250 mm, 5
      microm), using acetonitrile-water (90:10) as the mobile phase at a flow rate of
      0.8 mL x min(-1). The detection wavelength and column temperature were set at 205
      nm and 28 degrees C, respectively. RESULT: The calibration curves of pomolic
      acid, hawthorn acid, corosolic acid, oleanolic acid and ursolic acid were linear
      over the ranges of 0.096 0-2.400, 0.1230-3.075, 0.2420-6.050, 0.2830-7.075 and
      0.2730-6.825 microg (r = 0.9998, 0.9997, 0.9999, 0.9995, 0.9999), respectively.
      The average recoveries were 98.43%, 98.13%, 100.6%, 98.19% and 99.15%%,
      respectively, with RSD (n=6) being 1.3%, 0.67%, 1.2%, 0.87% and 0.43%.
      CONCLUSION: The proposed method is so simple and highly reproducible that it
      promises to be applicable for determination of major triterpenic acids in S.
      chinensis.

PMID- 25850272
TI  - [Research on correlation between odor and chemical compounds of Lonicera
      japonica].
AB  - This study aims to investigate the relationship between odor and contents of the
      chemical compounds in Lonicera japonica, including chlorogenic acid, galuteolin
      and polyphenols. High performance liquid chromatography (HPLC) was applied to
      determine the contents of chlorogenic acid and galuteolin in L. japonica. The
      ponptent of polyphenols was determined by UV-Vis Spectrophotometry. Electronic
      nose was used to extract and measure the odor of L. japonica. Then SPSS 17.0
      software was employed for data processing. There is a significant positive
      correlation between the comprehensive index value of aroma and the contents of
      chlorogenic acid and polyphenols. The regression equations have been established.
      However, the relationship between the comprehensive index value and the content
      of galuteolin is not obvious. This is proof that the odor of L. japonica has
      close connection with the chemical compounds. Therefore, this research offered a
      new method for initially determine or predict the content of the chemical
      composition in L. japonica,

PMID- 25850273
TI  - [Spectrum-effect relationship of Moutan cortex against lipopolysaccharide-induced
      acute lung injury].
AB  - This research is to study the relationship between HPLC fingerprints of Moutan
      Cortex, Paeoniae Radix Rubra and Paeoniae Radix Alba and their activity on
      lipopolysaccharide-induced acute lung injury. HPLC fingerprints of each extract
      of Moutan Cortex,Paeoniae Radix Rubra and Paeoniae Radix Alba were established by
      an optimized HPLC-MS method. The activities of all samples against protein and
      tumor necrosis a factor were tested by the model of lipopolysaccharide-induced
      acute lung injury. The possible relationship between HPLC-MS fingerprints and the
      activitieswere deduced by the Partial least squares regression analysis method.
      Samples were analyzed by HPLC-MS/MS to identify the major peaks. The results
      showed that each sample had some effect on acute lung injury. Four components
      with a lager contribution rate of efficacy were calculated by the research of
      spectrum-effect relationship. Moutan Cortex exhibited good activity on acute lung
      injury, and gallic acid, paeoniflorin, galloylpaeoniflorin and paeonol were the
      main effective components.

PMID- 25850274
TI  - [Application of near infrared spectroscopy to identify authenticity of Polygonum
      multiflorum].
AB  - OBJECTIVE: To establish a near-infrared qualitative analysis model to identify
      the authenticity of Polygonum multiflo- rum and distinguish processed products
      Polygoni Multiflori Radix. METHOD: The NIR spectra were peformed on over 30
      batches of P. multiflorum and Polygoni Multiflori Radix samples and the
      adulterants Cynanchum bungei, Pteroxygonum giraldii, Polygonum cillinerve to
      establish the qualitative discriminant model and the conformity test model of
      Polygonum multifiorum , and cluster analysis was used to analyze the samples from
      different origins. RESULT: The model is able to identify correctly P. multiflorum
      with its counterfeit, and distinguish between P. multiflorum and Polygoni
      multiflori Radix. CONCLUSION: Near-infrared spectroscopy can be applied in the
      identification of P. multiflorum, which could be used to screen Chinese herbal
      medicine preliminarily.

PMID- 25850275
TI  - [Protective effect of combined administration of active ingredients of Danhong on
      cerebral micro-vascular endothelial cell injured by hypoxia].
AB  - To study the protective effect of combined administration of active ingredients
      of Danhong on cultured primary mice's brain microvascular endothelial cells
      (rBMECs) injured by hypoxia. Primary mice's brain micro-vascular endothelial
      cells were cultured to establish the 4 h hypoxia model. Meanwhile, active
      ingredients (protocatechuic aldehyde, salvianolic acid B, hydroxysafflor yellow A
      and tanshinol) of Danhong were administered in rBMECs. The non-toxic dosage was
      determined by MTT. The leakage of lactate dehydrogenase(LDH), cell superoxide
      dismutase (SOD) activity and MDA level were detected by the colorimetric method.
      The expressions of ICAM-1, MMP-9, P53 mRNA were detected by RT-PCR method.
      Changes in rBMECs cell cycle and early apoptosis were detected by flow cytometry.
      Danhong's active ingredients and prescriptions 1, 2, 3, 7, 8, 9 could be combined
      to significantly restrain LDH in hypoxic cells supernatant. Prescriptions 1, 2,
      3, 7, 8, 9 could significantly enhance SOD activity in anoxic cells;
      Prescriptions 1, 2, 3, 8, 9 could significantly decrease the MDA level;
      Prescriptions 1, 2, 6, 7, 9 could significantly inhibit the early rB-MECs
      apoptosis induced by hypoxia. After hypoxia, the up-regulated P53 mRNA expression
      could cause retardation in G, phase and promote cell apoptosis. This proved that
      the regulatory function of P53 gene lay in monitoring of calibration points in G,
      phase. Prescriptions 1, 2, 5, 6, 7, 8, 9 could significantly down-regulate the
      P53 mRNA expression; Prescriptions 1, 4, 7, 8, 9 could significantly down
      regulate the ICAM-1 mRNA expression; Prescriptions 1, 3, 6, 9 could significantly
      down-regulate the MMP-9 mRNA expression. The combined administration of Danhong's
      active ingredients showed a significant protective effect on primary cultured
      rBMECs injury induced by hypoxia Its mechanism may be related to the enhancement
      of cellular antioxidant capacity and the inhibition of inflammatory response and
      cell apoptosis. This study could provide ideas for researching prescription
      compatibility, and guide the clinical medication.

PMID- 25850276
TI  - [Huanglian jiedu decoction active fraction protects ipsilateral thalamus injury
      in MCAO rats through regulating astrocytes].
AB  - OBJECTIVE: To observe the protective effects of the Huanglian Jiedu decoction
      aqueous extract and its active fraction, which consists of total alkaloids, total
      flavonoids and total iridoid, on the thalamus of cerebral ischemia in rats.
      METHOD: The rat model of middle cerebral artery occlusion (MCAO) was chosen. Male
      SD rats were randomly divided into sham-operation group, model group, aqueous
      extract group (800 mg x kg(-1)), total alkaloids group(44 mg x kg(-1)), total
      flavonoids group (50 mg x kg(-1)) and the total iridoid group (80 mg x kg(-1)).
      The rats were administered the appropriate drugs intragastrically once a day, for
      7 days after surgery. An equivalent volume of saline was given in the sham
      surgery and model groups. The HE staining was adopted to observe the pathological
      changes. Determination of Glu and gamma-GABA in thalamus were detected by HPLC
      with fluorescence detection. The expression of GAD65 was examined with
      immunohistochemistry and double staining with uorescent-conjugated antibodies
      against GFAP and Cx43 was chosen in this study. RESULT: The neurons degenerated
      in MCAO rats after cerebral ischemia 7 d. The content of Glu, gamma-GABA
      decreased (P < 0.05), the expression of GAD65 reduced (P < 0.05) and the
      expression of GFAP and Cx43 increased (P < 0.01) in thalamus of rats compared
      with sham-operation group. Huanglian Jiedu decoction aqueous extract, total
      alkaloids, total flavonoids and total iridoid reduced the degeneration of
      neurons. Total flavonoids could promote the expression of GAD65 (P < 0.05) and
      decrease the expression of GFAP and Cx43 (P < 0.01) in thalamus compared with
      model group while it could also increased the content of Glu,gamma-GA BA to
      normal levels. Compared with model group, Huanglian Jiedu decoction aqueous
      extract, total alkaloids and total iridoid could raise the expression of Cx43,
      and Huanglian Jiedu decoction aqueous extract could also increase the expression
      of GAD65 (P < 0.05). The expression of GFAP in Huanglian Jiedu decoction aqueous
      extract group, total alkaloids group and total iridoid group were not different
      compared with model group while the content of gamma-GABA decreased (P < 0.05)
      compared with sham-operation group. CONCLUSION: The degeneration of nerve cells,
      the reduction of neurotransmitter amino acids content, the aberrant activation of
      astrocytes and the abnormal expression of GFAP and Cx43 will appear in thalamus
      of MCAO rats after ischemia. Huanglian Jiedu decoction total flavonoids could
      relieve the injury of nerve cell through inhibiting the abnormal activation of
      astrocytes and regulating the expression of GFAP and GAD65.

PMID- 25850277
TI  - [Method of traditional Chinese medicine formula design based on 3D-database
      pharmacophore search and patent retrieval].
AB  - By using the pharmacophore model of mineralocorticoid receptor antagonists as a
      starting point, the experiment stud- ies the method of traditional Chinese
      medicine formula design for anti-hypertensive. Pharmacophore models were
      generated by 3D-QSAR pharmacophore (Hypogen) program of the DS3.5, based on the
      training set composed of 33 mineralocorticoid receptor antagonists. The best
      pharmacophore model consisted of two Hydrogen-bond acceptors, three Hydrophobic
      and four excluded volumes. Its correlation coefficient of training set and test
      set, N, and CAI value were 0.9534, 0.6748, 2.878, and 1.119. According to the
      database screening, 1700 active compounds from 86 source plant were obtained.
      Because of lacking of available anti-hypertensive medi cation strategy in
      traditional theory, this article takes advantage of patent retrieval in world
      traditional medicine patent database, in order to design drug formula. Finally,
      two formulae was obtained for antihypertensive.

PMID- 25850278
TI  - [Mechanism study on preventive and curative effects of buyang huanwu decoction in
      Qi deficiency and blood stasis diseases based on network analysis].
AB  - In this study, researchers adopted the network analysis method to study Buyang
      Huanwu decoction at three levels, namely chemical ingredients, targets and
      diseases, and discovered the potential effect of Buyang Huanwu decoction in
      cancer treatment. Besides, they analyzed the "target-target" network of Buyang
      Huanwu decoction based on diseases, calculated four network indexes, namely node
      centrality, closeness centrality, betweenness centrality and eigenvector
      centrality for a comprehensive evaluation on the importance and significance of
      each target in the network. Afterwards, key targets of Buyang Huanwu decoction
      were excavated to obtain two important targets--COX-2 and PPAR-gamma, which may
      be important targets involved in the qi deficiency and blood stasis diseases.
      Meanwhile, the two targets were the basis to build the core network of "chemical
      component-target-disease" of Buyang Huanwu decoction, which provided reference
      for further studies on the effect of Buyang Huanwu decoction in treating qi
      deficiency and blood stasis diseases. According to the study, the network
      analysis method was helpful to excavate potential targets Buyang Huanwu decoction
      in treating qi deficiency and blood stasis diseases, and could provide
      methodological reference for revealing the mechanism of Buyang Huanwu decoction
      at multiple levels, with a guiding significance for interpreting mechanisms of
      traditional Chinese medicinal formulae and developing new drugs.

PMID- 25850279
TI  - [Effects of methyl cantharidimide tablets on urinary protein and enzymes in
      Beagle dogs].
AB  - OBJECTIVE: To investigate the nephrotoxic effects of methyl cantharidimide
      tablets on urinary protein and enzymes in Beagle dogs. METHOD: Beagle dogs were
      randomly divided into negative control group(blank tablet), methyl cantharidimide
      tablets group (6.11,12.21, 24.42 mg x kg(-1)), continuously 30 days of oral
      adminiStration, once a day. The drug and control group were collected and
      determined fresh urine in 1, 2, 3 and 4 weeks of the administration; Serum urea
      nitrogen (BUN), creatinine (Crea), total protein (TP) and albumin (ALB) as well
      as sodium, potassium, chloride electrolyte were determined on 15 and 30 days of
      the administration; Urine albumin (mAlb), kidney injury molecule-1 (KIM-1),
      neutrophil gelatinase-associated lipocalin( NGAL), N-acetyl-beta-D
      glucosaminidase (NAG), clusterin, beta2-microglobulin (beta2-MG), alpha1
      microglobulin (alpha1-MG), alanine aminopeptidase( AAP) and im- munoglobulins IgG
      were tested on 15 and 30 days of the administration. RESULT: Compared with the
      control group, urine protein and white blood cells was significantly increased in
      each dose group. On 15 days of the administration, mAlb were higher in each dose
      group, KIM-1, NGAL, clusterin, NAG and AAP were significantly higher in high-dose
      group, while the middle and low dose group had no significant difference, as well
      as blood SCr and BUN no obvious abnormalities. On 30 days, mAlb, KIM-1,
      clusterin, NAG, AAP were increased in each dose group, appearing dose-effect
      relationship, beta2-MG and NGAL levels were significantly increased in high-dose
      group. Contents above indicators were increased with significant dose and time
      relationship, and serum BUN, Scr were correlated, suggesting that urine mAlb, KIM
      1, clusterin, NAG and AAP indicators that can sensitively respond the changes of
      proteins and enzymes in urine. CONCLUSION: Methyl cantharidimide tablets has a
      renal toxicity, urine mAlb, KIM-1, clusterin, NAG and AAP can be used as the
      early nephrotoxic biomarkers of methyl cantharidimide tablets.

PMID- 25850280
TI  - [Protective effect of astragaloside IV on oxidative damages of chang liver cell
      induced by ethanol and H2O2].
AB  - OBJECTIVE: To study the protective effect of astragaloside IV on oxidative
      damages of Chang Liver cells induced by ethanol and H2O2. METHOD: The alcoholic
      and nonalcoholic oxidative damage models were established on Chang Liver cells
      with ethanol and H2O2, respectively. The cells viabilities were detected by MTT
      assay, transaminase activity and antioxidant ability were detected by micro plate
      and colorimetric method, reactive oxide species (ROS) was detected by DCFH-DA
      fluorescent probe and cell cycle was detected by flow cytometry. DNA ladder
      method was used to detect apoptosis. RESULT: Both kinds of oxidative damage could
      decrease the viability and antioxidant enzyme activity of Chang Liver cells, and
      increase the transaminase activity and MDA content of extracellular fluid. The
      protective effects of astragaloside IV against those two kinds of oxidative
      damages were significant or extremely significant. Meanwhile, ethanol could
      decline the level of ROS significantly in the damaged cells, while H2O2 could
      increase it significantly. And the effect of astragaloside IV was to make ROS
      return to the normal level. Retardation of cell cycle progression of Chang Liver
      cells in G0/G1 induced by ethanol or H2O2 was relieved, and apoptosis was also
      inhibited. CONCLUSION: Astragaloside IV had protective effect on oxidative
      damages of Chang Liver cells induced by ethanol and H2O2.

PMID- 25850281
TI  - [Effects of component formula of Salviae Miltiorrhizae Radix et Rhizoma and
      Ginseng Radix et Rhizoma on cell proliferation, apoptosis and skeleton in lung
      cancer A549 cells].
AB  - This study aims to optimize the most effective component formula of Salviae
      Miltiorrhizae Radix et Rhizoma and Ginseng Radix et Rhizoma on lung cancer A549
      using the orthogonal design method, and to investigate its effects of the
      component formula on cell proliferation, apoptosis and cytoskeleton in lung
      cancer A549 cells. The orthogonal design method was introduced to optimize the
      most effective component formula of Salviae Miltiorrhizae Radix et Rhizoma and
      Ginseng Radix et Rhizoma on lung cancer A549 cells. CCK-8 assay and Real-time
      cell analysis were adapted to analyze the effect of component formula of Salviae
      Miltiorrhizae Radix et Rhizoma and Ginseng Radix et Rhizoma on A549 cells
      viability at different time and dose. Cell apoptosis was measured by Annexin V-
      FITC/PI double staining and flow cytometry. Cell skeleton protein F-actin was
      detected by high content screening (HCS). The optimizing component formula of
      Salviae Miltiorrhizae Radix et Rhizoma and Ginseng Radix et Rhizoma for total
      salvianolic acid, total saponins of panax ginseng and ginseng polysaccharide
      doses were 5, 10, 5 mg L(-1). CCK-8 assay and real-time cell analysis
      demonstrated that the component formula of Salviae Miltiorrhizae Radix et Rhizoma
      and Ginseng Radix et Rhizoma treatment could significantly decrease the A549 cell
      viability in both dose- and time-dependent manner compared with control group (P
      < 0.01). Moreover, the increase of cell apoptosis was detected by Annexin V
      FITC/PI double staining and flow cytometry when cells treated with the component
      formula, which indicating that the component formula of Salviae Miltiorrhizae
      Radix et Rhizoma and Ginseng Radix et Rhizoma could induce A549 cell apoptosis in
      a time-dependent manner compared with control group (P < 0.01). Furthermore,
      compared with control group, a significant decrease in A549 cell skeleton area
      was found in the component formula-exposed cells in the dose-dependent manner (P
      < 0.01). In summary, the component formula of Salviae Miltiorrhizae Radix et
      Rhizoma and Ginseng Radix et Rhizoma inhibits A549 cell proliferation by inducing
      cell apoptosis and decreasing cell microfilament formation. All of these results
      will be helpful to reveal antitumor mechanism of the component formula of Salviae
      Miltiorrhizae Radix et Rhizoma and Ginseng Radix et Rhizoma, which provides a
      basis for the exploration of antitumor mechanism of the component formula on lung
      cancer.

PMID- 25850282
TI  - [Research of anti-aging mechanism of ginsenoside Rg1 on brain].
AB  - Neurodegenerative disease is common and frequently occurs in elderly patients.
      Previous studies have shown that ginsenoside Rg1 was able to inhibit senescent of
      brain, but the mechanism on the brain during the treatment remains elucidated. To
      study the mechanism of ginsenoside Rg1 in the process of anti-aging of brain,
      forty male SD rats were randomly divided into normal group, Rg1 normal group,
      brain aging model group and Rg1 brain aging model group, each group with 10 rats
      (brain aging model group: subcutaneous injection of D-galactose (120 mg kg(-1)),
      qd for 42 consecutive days; Rg1 brain aging model group: while copying the same
      test as that of brain aging model group, begin intraperitoneal injection of
      ginsenosides Rg1 (20 mg x kg(-1)) qd for 27 d from 16 d. Rg1 normal group:
      subcutaneous injection of the same amount of saline; begin intraperitoneal
      injection of ginsenosides Rg1 (20 mg x kg(-1)) qd for 27 d from 16 d. Normal:
      injected with an equal volume of saline within the same time. Perform the related
      experiment on the second day after finishing copying the model or the completion
      of the first two days of drug injections). Learning and memory abilities were
      measured by Morris water maze. The number of senescent cells was detected by SA
      beta-Gal staining while the level of IL-1 and IL-6 proinflammatory cytokines in
      hippocampus were detected by ELISA. The activities of SOD, contents of GSH in
      hippo- campus were quantified by chromatometry. The change of telomerase
      activities and telomerase length were performed by TRAP-PCR and southern blotting
      assay, respectively. It is pointed that, in brain aging model group, the spatial
      learning and memory capacities were weaken, SA-beta-Gal positive granules
      increased in section of brain tissue, the activity of antioxidant enzyme SOD and
      the contents of GSH decreased in hippocampus, the level of IL-1 and IL-6
      increased in hippocampus, while the length of telomere and the activity of
      telomerase decreased in hippocampus. Rats of Rg1 brain aging group had their
      spatial learning and memory capacities enhanced, SA-beta-Gal positive granules in
      section of brain tissue decreased, the activity of antioxidant enzyme SOD and the
      contents of GSH increased in hippocampus, the level of IL-1 and IL-6 in
      hippocampus decreased, the length contraction of telomere suppressed while the
      change of telomerase activity increased in hippocampus. Compared with that of
      normal group, the spatial learning and memory capacities were enhanced in Rg1
      normal group, SA-beta-Gal positive granules in section of brain tissue decreased
      in Rg1 normal group, the level of IL-1 and IL-6 in hippocampus decreased in Rg1
      normal group. The results indicated that improvement of antioxidant ability,
      regulating the level of proinflammatory cytokines and regulation of telomerase
      system may be the underlying anti-aging mechanism of Ginsenoside Rg1.

PMID- 25850283
TI  - [Ginsenoside Rb1 upregulates expressions of GLUTs to promote glucose consumption
      in adiopcytes].
AB  - Previous studies have shown that ginsenoside Rb1 (Rb1), one of active components
      in ginseng, can activate insulin signaling pathway and promote translocation of
      glucose transporters (GLUTs) to increase glucose uptake in adipocytes. However,
      the effect of Rb1 on the expressions of GLUTs remains unknown. In this study, the
      effects of Rb1 on GLUT1 and GLUT4 were observed in 3T3-L1 adipocytes and
      epididymal adipose tissue of db/db obese diabetic mice. Male db/db mice were
      treated with Rb1 by intraperitoneal injection at the dosage of 20 mg x kg(-1) for
      14 d. Rb1 reduced HOMA-IR significantly (P < 0.05, n = 5), and FBG and FINS sowed
      declining trend after treatment with Rb1. Rb1 recovered the expressions of GLUT1
      and GLUT4 and phosphorylation of AKT in adipose tissue of db/db mice. In vitro,
      glucose consumption in 3T3-L1 adipocytes treated with 10 micromol x L(-1) Rb1 for
      24 h was elevated (P < 0.05, n=3), and mRNA of GLUT1 and GLUT4 were up-regulated
      (P < 0.05, n=3) and proteins of GLUT1 and GLUT4 were also increased. AKT was
      activated in adipocytes treated with Rb1 for 3 h. It can be concluded that
      ginsenoside Rb1 can up-regulate the expression of GLUTs in adipose tissue, in
      addition to activate insulin signalling pathway, which may partially account for
      its insulin sensitizing activity and regulating effect of glucose metabolism.

PMID- 25850284
TI  - [Effects of xuefu zhuyu decoction on antioxidant and drug-metabolizing enzymes in
      liver of rats].
AB  - Xuefu Zhuyu decoction (XFZYD) is a famous traditional Chinese medicine (TCM)
      formula, is widely used in the treatment of cardiovascular and cerebrovascular
      diseases in China over one hundred years. But its effect on antioxidant and drug
      metabolizing enzymes are unknown. This study was to observe the effects of Xuefu
      Zhuyu decoction (XFZYD) on the activities of antioxidant and drug metabolism
      enzymes (DMEs) in liver of rats. Male SD rats, treated with XFZYD at the dosage
      of 3.51, 7.02 and 14.04 g x kg(-1) per day for 15 days, serum were collected,
      tissue fluid, cytosols and microsomes isolated from liver tissues were prepared
      by centrifugation according to the standard procedure, the activities of
      antioxidant enzymes and drug-Metabolizing Enzymes were determined by UV-V is
      spectrophotometer. In serum, the activities of AST was not significantly affected
      by the treatment with XFZYD, at the high- est dose, the levels of ALT, Cr and BUN
      were significantly decreased (P < 0.05). GPX were significantly increased at the
      dose of 7.02, 14.04 g x kg(-1) (P < 0.05), CAT were significantly increased at
      the highest dose (P < 0.05). T-SOD was not significantly af- fected by this
      treatment. In the liver tissue, GPX was significantly increased at the dose of
      3.51, 7.02 g x kg(-1) (P < 0.05), GST, CAT and T-SOD were not significantly
      affected following this treatment. In cytosols, GST was significantly increased
      at the dose of 3.51 g x kg(-1) (P < 0.05), T-SOD was remarkable induced at the
      dose of 3.51 and 7.02 g x kg(-1) (P < 0.05). In microsomes, XFZYD had no
      significant effect on Cytochromeb5, NADPH-Cytochrome P450 reductase, CYP3A,
      CYP2E1 and UGT, XFZYD significantly in- duced GST at the dose of 3.51 and 7.02 g
      x kg(-1) (P < 0.05), and the level of GSH were significantly increased by XFZYD
      at the dose of 3.51, 7.02 and 14.04 g kg(-1) (P < 0.05). These findings suggest
      XFZYD can induce the activities of GPX, CAT, SOD, GST and increase GSH level in
      liver of rats, which indicate XFZYD may have detoxification and antioxidant
      functions.

PMID- 25850285
TI  - [Effect of oligosaccharide esters and polygalaxanthone Ill from Polygala
      tenuifolia willd towards cytochrome P450].
AB  - Five compounds (tenuifoliside C, tenuifoliside D, telephiose A, telephiose C and
      polygalaxanthone III) from polygala tenuifolia wild were incubated together with
      CYP probe substrate in human liver microsomes to investigate the inhibitory
      effect towards CYP450 enzyme. Phenacetin (CYP1A2), coumarin (CYP2A6), paclitaxel
      (CYP2C8), diclofenac (CYP2C9), S-mepheriytoin (CYP2C19), dextromethorphan
      (CYP2D6), chlorzoxazone (CYP2E1), midazolam (CYP3A) were selected as the isoforfn
      specific substrate. And the formation of paracetamol, 7-hydroxycoumarin, 6alpha
      hydroxy paclitaxel, 4'-hydroxydiclofenac, dextrorphan, 6-hydroxychlorzoxazone, 1'
      hydroxymidazolam, 4'-hydroxymephenytoin were detected respectively to measure the
      effect towards CYP450 by high-pressure liquid chromatography (HPLC). The result
      shows that five compounds from polygala tenuifolia willd significantly inhibit
      chlorzoxazone 6-hydroxylation catalyzed by CYP2E1, while showed no effect towards
      CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A. And IC50 value was 38.73,
      54.14, 61.77, 62.22, 50.56 micromol x L(-1), respectively.

PMID- 25850286
TI  - [Analysis on medication rules of state medical master yan zhenghua's
      prescriptions that including Polygoni Multiflori Caulis based on data mining].
AB  - The prescriptions including Polygoni Multiflori Caulis that built by Pro. Yan
      were collected to build a database based on traditional Chinese medicine (TCM)
      inheritance assist system. The method of association rules with apriori algorithm
      was used to achieve frequency of single medicine, frequency of drug combinations,
      association rules between drugs and core drug combinations. The datamining
      results indicated that in the prescriptions that including Polygoni Multiflori
      Caulis, the highest frequency used drugs were parched Ziziphi Spinosae Semen,
      Ostreae Concha, Ossis Mastodi Fossilia, Salviae Miltiorrhizae Radix Et Rhizoma,
      Paeoniae Rubra Radix, and so on. The most frequent drug combinations were
      "Polygoni Multiflori Caulis-parched Ziziphi Spinosae Semen", "Ostreae Concha
      Polygoni Multiflori Caulis", and "Polygoni Multiflori Caulis-Ossis Mastodi
      Fossilia". The drug association rules of confidence coefficient 1 were "Ostreae
      Concha-->Polygoni Multiflori Caulis", "Poria-->Polygoni Multiflori Caulis",
      "parched Ziziphi Spinosae Semen-->Polygoni Multiflori Caulis", and "Paeoniae Alba
      Radix-->Polygoni Multiflori Caulis". The core drug combinations in the treatment
      of insomnia were Ossis Mastodi Fossilia, Polygoni Multiflori Caulis, Salviae
      Miltiorrhizae Radix et Rhizoma, Ostreae Concha, Polygalae Radix, Margaritifera
      Concha, Poria, and parched Ziziphi Spinosae Semen. And the core drug combinations
      in the treatment of obstruction of Qi in chest were Salviae Miltiorrhizae Radix
      Et Rhizoma, Polygoni Multiflori Caulis, parched Ziziphi Spinosae Semen,
      Trichosanthis Fructus, Allii Macrostemonis Bulbus, and Paeoniae Rubra Radix.

PMID- 25850287
TI  - [Analysis on formula raw materials application of health food containing
      Gardeniae fructus].
AB  - In this article we built formula database of health food containing Gardeniae
      Fructus with Traditional Chinese Medicine Inheritance Support System (V2.0). And
      on this basis, use data mining method such as association rules of the software,
      to analyze commonly used formula raw materials or materials combination of
      formula containing Gardeniae Fructus and raw material application having assisted
      function formula to protect chemical liver injury. The result shows that of the
      71 health food formulas containing Gardeniae Fructus, most used materials are
      Gardeniae Fructus, Lycii Fructus, Angelica Sinensis Radix, Poria and so on.
      Commonly used materials combination mostly are Gardeniae Fructus and Lycii
      Fructus, Gardeniae Fructus and Angelica Sinensis Radix, Gardeniae Fructus and
      Poria, Gardeniae Fructus and Paeonia. There are nearly 18 healthcare functions of
      the health food containing Gardeniae Fructus, and most of these are assisted
      functions to protect chemical liver injury, and then immune modulating function.
      Of 23 formulas containing Gardeniae Fructus having assisted function formula to
      protect chemical liver injury, Gardeniae Fructus usually combined with
      traditional Chinese medicine which nourishs blood and liver such as Pueraria,
      Lycii Fructus, Hawthorn, Paeonia and Turnjujube. Analyzing formula raw materials
      application of health food containing Gardeniae Fructus contributes a lot to the
      further development and utilization.

PMID- 25850288
TI  - [Development of Chinese herbal pieces and analysis of problems of total quality
      management].
AB  - Chinese herbal pieces are a key factor to protecting the quality of the clinical
      efficacy of traditional Chinese medicine (TCM), and it is one of the basic
      elements of ensuring the quality of TCM and people's usage safety. However,
      Chinese herbal pieces has massive problem such as adulteration and counterfeit,
      dyeing and weighting, pesticide residues, heavy metals in excess of the
      standards, and all the issues are repeated excessive in the clinic treatment.
      These issues impacted sound development of production, management and use of TCM,
      but also brings common people hidden trouble for the clinical safety of
      medication. Protect and improve the quality of the Chinese herbal pieces demand
      that continue improve quality system, in-depth scientific research, and
      strengthen self-discipline and other factors. So it is fundamentally to ensure
      good quality of Chinese herbal pieces with the color, taste and shape by
      systematic supervision to it from the source, production, management and
      research, with strengthened implementation and en- forcement of the "3G".

PMID- 25850289
TI  - [The cellular mechanisms and regulation of metastasis formation].
AB  - Recent data obtained at the junction of biochem: istry, molecular and cell
      biology and experimental oncology, showed that the formation of secondary foci of
      tumor growth during cancer progression--metastasis formation--is a highly
      determinate and regulated process. This process includes on the one hand the
      appearance of metastatic population of cells with special characteristics that
      allow their dissemination and seeding in distant organs and on the other.hand the
      formation of specific attractive micro environment in target organs. These cells
      show the ability to switch their motility to the most effective mode depending on
      the properties of the surrounding tissues (plasticity), appearance of specific
      receptors on the cell surface, which enhance their directed migration to target
      organs and acquisition of some characteristics of stem cells, allowing them to
      survive and reproduce in alien microenvironment. These alterations are strongly
      coordinated with development of a specific nichein the target organ which
      stimulates initiation and growth of a future metastasis, so-called premetastatic
      niche. In this review we analyzed recent data concerning mechanisms which
      regulate the emergence of metastatic population of cells, development of
      premetastatic niches and coordination of these processes:.

PMID- 25850290
TI  - [Cellular targets of antitumor ribonucleases].
AB  - Some ribonucleases (RNases) produce selective toxic effect on the cancer cells.
      The mechanism of this antitumor activity remains largely unclear. The subject of
      this review is the RNases interaction with cellular components, resulting in the
      induction of apoptosis of tumor cells. Cell surface structures, which are
      potential acceptors of the exogenous RNase are discussed: acidic lipids and
      glycoproteins, heparansulfate-containing proteoglycans, actin, and RNA-associated
      proteins. Cell membranes of normal and malignant cells differ according to the
      composition of these components, which largely determines the selectivity of
      RNases for the latter. Different types of RNA are examined as intracellular
      targets of the RNases activity, evidence is presented demonstrating the
      possibility of exogenous RNases intervening in the process of RNA interference.
      The role of potassium channels, NF-kappaB-dependent.signaling pathway and various
      caspases in apoptosis induced by exogenous RNases is discussed. Evidence is also
      presented showing that the sensitivity of cells to exogenous RNases is linked to
      the expression of certain oncogenes, namely RAS, KIT, AML1-ETO. It is suggested
      that discovering the details of the mechanisms of RNases cytotoxic effect in
      malignant cells susceptible to their activity, will in the future serve as a
      foundation to developing new tools of targeted anticancer therapy.

PMID- 25850291
TI  - [Multifunctional protein complex NAC (nascent polypeptide associated complex].
AB  - The functions of the evolutionary conservative complex NAC (Nascent polypepetide
      Associated Complex) and its subunits are discussed. The heterodimeric NAC protein
      contains alpha- and beta-subunits and is found to be reversibly bounded to the
      ribosome in all eukaryotes, from yeast to humans. NAC contacts the nascent
      polypeptide and protects it from proteolysis. NAC participates in polypeptide
      chain folding and modulates protein secretion and transmembrane protein
      formation. Mutations and deletions of genes, encoding NAC subunits are lethal in
      early development of multicellular eukaryotes. NAC is involved in the ribosome
      biogenesis. The beta-subunit interacts with caspase-3 and may be involved in the
      regulation of the apoptotic pathway. The variants of NAC proteins can be
      considered as chaperone complexes, involved in the response of the cell and the
      organism to stress factors, as well as regulators of apoptosis. The genes
      encoding beta-subunits are rapidly evolved, their duplications cause the
      formation of tissue specific beta-subunit variants with a different number of
      putative caspase cleavage sites. The homodimer of alpha-subunits is shown to be
      the RNA/DNA binding protein and acts as a transcriptional cofactor. The diversity
      in the functioning of NAC is a prime example of a protein that performs a variety
      of biological functions (moonlighting protein).

PMID- 25850292
TI  - [MicroRNA and cancer].
AB  - Review is devoted to analysis of the role of microRNA in progression of human
      tumors. The following aspects of this problem are discussed: general
      characteristics of microRNA, expression pattern of these RNAs in human tumors and
      specificity of this expression, putative role of microRNAs as oncogenes and tumor
      suppressors for tumor growth, participation of microRNAs in induction of
      transformed phenotypes of tumor cells, possible role of microRNAs for early
      diagnosis of the disease and prognosis.

PMID- 25850293
TI  - [Genotyping of BRCA1, BRCA2 and CHEK2 germline mutations in Russian breast cancer
      patients using diagnostic biochips].
AB  - Germline mutations of BRCA1/2 genes cause the predisposition of their carriers to
      breast or/and ovary cancers (BC or/and OC) during the lifetime. Identification of
      these mutations is a basis of molecular diagnosis for BC susceptibility. Rapid
      genotyping technique using microarrays for identification of BRCA1 185delAG,
      300T>G, 4153delA, 5382insC mutations and 4158 A>G sequence variant; BRCA2 695insT
      and 6174delT mutations; 1100delC mutation in CHEK2 gene was applied for 412
      randomly collected breast cancer samples from the central region of European area
      of Russia. In 25 (6.0%) patients (6.0%) BC was associated with other tumours: OC,
      cervical cancer, colorectal cancer etc. BRCA1/2 and CHEK2 mutations were found in
      33 (8.0%) BC patients. The most frequent mutation was BRCA1 5382insC, occurred in
      16 (3.9%) BC patients, and CHEK2 1100delC, revealed in 7 (1.7%) BC patients. An
      application of diagnostic BC-microarray for genetic testing of BRCA1/2 and CHEK2
      founder mutations has been discussed.

PMID- 25850294
TI  - [Analysis of genetic determinants of multidrug and extensively drug-resistant
      Mycobacterium tuberculosis using oligonucleotide microchip].
AB  - Steadily growing resistance of the tuberculosis causative agent towards a broad
      spectrum of anti-tuberculosis drugs calls for rapid and reliable methods for
      identifying the genetic determinants responsible for this resistance. In this
      study, we present a biochip-based method for simultaneous identification of
      mutations within rpoB gene associated with rifampin resistance, mutations in
      katG, inhA, ahpC genes responsible for isoniazid resistance, mutations within the
      regions of gyrA and gyrB genes leading to fluoroquinolones resistance, and
      mutations in the rrs gene and the eis promoter region associated with the
      resistance to kanamycin, capreomycin and amikacin. The oligonucleotide microchip,
      as the core element of this assay, provides simultaneous identification of 99
      mutations in the format "one sample--one PCR--one microchip", and it makes it
      possible to complete analysis of multi-drug-resistant and extensively drug
      resistant tuberculosis within a single day. The tests on 63 Mycobacterium
      tuberculosis clinical isolates with different resistance profiles using the
      developed approach allows us to reveal the spectrum of drug-resistance associated
      mutations, and to estimate the significance of the inclusion of extra genetic
      loci in the determination of M. tuberculosis drug resistance.

PMID- 25850295
TI  - [Association of polymorphisms in toll-like receptor genes with atopic dermatitis
      in the Republic of Bashkortostan].
AB  - Atopic dermatitis (AD) is a prevalent chronic inflammatory skin disease
      developing as a result of the interaction between genetic predisposition and
      environmental factors. Considerable role in allergic diseases development is
      played by polymorphisms of genes of pattern-recognition receptors (PRR) which are
      capable of recognizing conservative standard molecular structures (patterns)
      unique for large pathogen groups. In this study polymorphic variants of PRR genes
      -Toll-like receptors (TLR1, TLR2, TLR4, TLR5, TLR6, TLR9, TLR10), NOD-like
      receptors (NOD1, NOD2), lipopolysaccharide receptor CD14 gene, and C11orf30 and
      LRRC32 genes, located in 11q13.5 region, have been investigated in AD patients
      and control subjects from the Republic of Bashkortostan. An association of TLR1
      (rs5743571 and rs5743604), TLR6 (rs5743794) and TLR10 (rs11466617) with AD was
      found. Our results confirm an important role of the innate immune system in the
      pathogenesis of AD and the significance of polymorphisms within the Toll-like
      receptor 2 subfamily genes in AD development.

PMID- 25850296
TI  - [Effect of tripeptide Pro-Gly-Pro on rat brain transcriptome in focal ischemia].
AB  - Biologically active regulatory peptide, tripeptide Pro-Gly-Pro (PGP) was used as
      C-terminal fragment for peptide drugs Semax and Selank. In recent years the
      independent effects of PGP were observed. The question was raised, whether PGP
      contributes to the effects ofpeptide drugs containing PGP as a fragment. The
      genome-wide analysis was performed to investigate the influence of PGP on the
      transcriptome of ischemic rat brain cortex tissues. The gene expression
      alterations caused by the action of the tripeptide PGP were compared with the
      gene expression of the control group "ischemia" at 3 and 24 h after permanent
      occlusion of left middle cerebral artery. The altered expression was detected for
      29 genes at 3 h and 57--at 24 h. The proteins encoded by these genes have variety
      of functions: cytokines, transport proteins, transcription factors, transmembrane
      receptors, etc. Biological processes, which are related to the genes with altered
      expression, were distinguished. The influence of PGP on the diversity of
      biological processes in different systems of the organism is demonstrated for the
      first time. The process "Immune response" was the most statistically notable at
      24 h after occlusion. The expression of the immune system genes was predominately
      down regulated.

PMID- 25850297
TI  - [Functional characterization of two novel splicing mutations in glucokinase gene
      in monogenic diabetes MODY2].
AB  - Two novel mutations in glucokinase (GCK) gene-G to C substitution at -1 position
      of intron 7 acceptor splice site (c. 864-1G>C) and synonymous substitution c.
      666C>G (GTC>GTG, p.V222V) in exon 6--were identified in patients with monogenic
      diabetes MODY2 (Maturity Onset Diabetes of Young). GCK minigenes with these
      mutations were constructed. Analysis of splicing products upon transfection of
      minigenes into human embryonic cell line HEK293 has shown that each of these
      nucleotide substitutions impair normal splicing. Mutation c.864-1G>C blocks the
      usage of normal acceptor site which activates cryptic acceptor splice sites
      within intron 7 and generates aberrant RNAs containing the portions ofintron 7.
      Synonymous substitution c.666C>G creates novel donor splice site in exon 6 that
      leads to formation of defective GCK mRNA with deletion of 16 nucleotides of exon
      6. Analysis of in vitro splicing of minigenes confirms the inactivating action of
      novel mutations on glucokinase expression.

PMID- 25850298
TI  - [The 3'-UTR polymorphism of dopamine transporter gene in hadza and datoga males].
AB  - The study of VNTR-polymorphism and the molecular struc ture of 3'-UTR of the
      dopamine transporter gene (DAT1/SLC6A3) was performed in hadza and datoga males.
      It was shown that hadza and datoga differed in allele and genotype frequencies.
      Allele with 9 repeats in 3'-UTR is more common in hadza as well as homozygous
      genotype DAT19/9. Allele with 10 repeats is more common in datoga as well as
      homozygous genotype DAT1 10/10. The molecular structure of the DAT alleles with
      3, 8 and 12 repeats was determined for the first time. In addition it was found
      that DAT1 allele with 11 repeats in datoga significantly differed from previously
      described ones in other populations in repeats type and arrangement. We suggest
      that variations of the repeats num ber and type in the 3'-UTR of allelic variants
      may affect the dopamine transporter gene function.

PMID- 25850299
TI  - [Sub-celluiar localization of PELPK1 in Arabidopsis thaliana as determined by
      translational fusion with green fluorescent protein reporter].
AB  - PELPK1, a novel Arabidopsis thaliana gene was earlier annotated to encode a
      protein of sub-family, PELPK under hydroxyproline-rich glycoprotein (HRGP) super
      family of proteins. Previous bioinformatics and computational analyses predicted
      PELPK1 to contain an amino-terminal signal peptide destined towards the secretory
      pathway. In the present study, transgenic plants were developed harboring a
      translational fusion construct comprising of PELPK1 coding sequence (PELPK1-CDS)
      and green fluorescent protein (GFP) reporter to determine the localization of
      PELPK1 in Arabidopsis plants. By employing the techniques of confocal laser
      scanning microscopy, immunolabeling of GFP with quantum dot (Q-dot), and
      transmission electron microscopy (TEM), it is shown that the translational fusion
      product is predominantly deposited to the cell wall. These results are in
      agreement with the earlier bioinformatics prediction that the PELPK1 is
      transported via the secretory pathway.

PMID- 25850300
TI  - [Kinetics of heat shock response upon disfunction of general transcription factor
      (HSF)].
AB  - The heat shock transcription factor (HSF) is a universal activator of hsp gene
      expression in eukaryotes. A temperature sensitive Drosophila melanogaster strain
      (hsf4) with a mutation in the hsfgene was originally described as a strain
      lacking the transcription of hsp genes in response to heat shock. Our results
      demonstrated that physiological function of HSF4 is not fully abrogated after
      heat exposure and is able to recover even after severe heat stress, causing the
      induction of hsp gene expression. We have studied the kinetics of accumulation
      and degradation of hsp gene products at transcriptional and translational levels
      and shown that induction of hsp genes, particularly hsp68, in mutant strain is
      weaker than that in the wild type. Thus, despite the fact that the HSF4 causes a
      delayed ac- tivation of hsp, response to heat shock in hsf4 strain remains
      defective.

PMID- 25850301
TI  - [Modification of [PSI+] prion properties by the combination of amino acid changes
      within Sup35 protein N-domain].
AB  - [PSI+] prion is an amyloid isoform of a release factor Sup35p (eRF3). The
      structure of these protein aggregates remains unclear despite a long term history
      of prion amyloids investigations. The N-terminal domain of Sup35p (which is
      responsible for a propagation of prion) shapes superpleated beta-structure,
      according to modern concepts. Recently we constructed five double mutations
      within SUP35 sequence encoding the N-terminal prion-forming domain and
      investigated properties of mutant proteins. Mutations sup35-M1 (YQ46-47KK) and
      sup35-M2 (QQ61-62KK) lead to [PSI+] prion loss, while other mutant alleles (sup35
      M3 QQ70-71KK; sup35-M4 QQ80-81KK; sup35-M5 QQ89-90KK) maintained prion. For the
      detail analysis of effects of mutant alleles on Sup35p aggregation we
      characterized propagation and properties of [PSI] prion in yeast strains bearing
      different mutant allele combinations. The data obtained have refined a supposed
      organization of beta-sheets forming by different regions of Sup35p prion-forming
      domain within amyloid. Also we obtained evidences that mutant sup35-M2 and sup35
      M4 alleles change structure of prion aggregates. The prion destabilization by
      these mutations possibly is connected with decrease of heteroaggregate
      fragmentation by chaperones.

PMID- 25850302
TI  - [In silico structural characterization and molecular docking studies of first
      glucuronoxylan-xylanohydrolase (Xyn30a) from family-30 glycosyl hydrolase (GH30)
      from Clostridium thermocellum].
AB  - CtXynGH30 is a carbohydrate active modular enzyme and component of cellulosome of
      Clostridium thermocellum. The full length CtXynGH30 contains an N-terminal
      catalytic module named as Xyn30A and a family 6 carbohydrate binding module
      (CBM6) at C-terminuis. Xyn30A was modeled by computer program Modeller9v8 taking
      crystal structure of XynC from B. subtilis as a template to generate the
      molecular model. Model refinement was done using energy minimization by
      implementing steepest descent algorithm with GROMOS96 43al force field. Quality
      assessment by Ramachandran plot showed that 91% amino acids lie in most
      favourable region and 9% in additional allowed region. Structural analysis
      depicted that Xyn30A has a (beta/alpha)8 barrel fold. Ad- ditionally, it had a
      beta-strand rich structure called 'side beta-structure' attached with main
      catalytic core. Structural superimposition reflected that Glu136 act as a
      catalytic acid/base while Glu225 act as a catalytic nucleophile. Multiple
      sequence alignment showed that these catalytic residues are conserved within the
      family. The docking results showed that these residues display polar interaction
      with linear and substituted xylo-oligosaccharides. The binding interaction of
      ligands depicted that aromatic amino acids Trp81, Tyr139, Trp143, Phe172, His198,
      Tyr200, Tyr227, Trp264 and Tyr265 create binding site pocket around the active
      site. We report overall structural feature, conserved active site residues and
      enzymeligand docking of first glucuronoxylan-xylanohydrolase (Xyn30A) of family
      30 glycosyl hydrolase (GH30) from Clostridium thermocellum.

PMID- 25850303
TI  - [Combining protein-protein interactions information with support vector machine
      to identify chronic obstructive pulmonary disease related genes].
AB  - Chronic obstructive pulmonary disease (COPD) is a complex human disease with a
      higher mortality. So far, the studies to COPD have not been well characterized
      despite the well-documented role of cigarette smoking in the genesis of COPD. In
      recent years, microarray analyses have help to identify some potential disease
      related genes. However, the low reproducibility of many published gene signatures
      has been criticized. It therefore suggested that incorporation of network or
      pathway information into prognostic biomarker discovery might improve the
      prediction performance. In this analysis, we combined protein-protein
      interactions (PPI) information with support vector machine (SVM) method to
      identify potential COPD-related genes that would allow one to distinguish
      accurately severe emphysema from non-/mildly emphysematous lung tissue. We
      identified 8 COPD-related feature genes. When compared with another SVM method
      which did not use the prior PPI information, the prediction accuracy was
      significantly enhanced (AUC is increased from 0.513 to 0.909). On the base of
      results obtained one can suppose that incorporating network of prior knowledge
      into gene selection methods significantly improves classification accuracy.
      Consequently, the gene expression profiles from human emphysematous lung tissue
      may provide insight into pathogenesis, and a good classify prediction algorithm
      based on prior biology knowledge can further strengthen this performance.

PMID- 25850304
TI  - [Universal modular system for in vitro screening of potential inhibitors of HIV-1
      replication].
AB  - Here we describe a system based on recombinant lentiviral vectors for the safe
      screening of potential anti-HIV drugs. The system allows to evaluate the
      sensitivity of HIVl-1 reverse transcriptase and integrase (wild-type as well as
      mutant forms of these enzymes detected in drug-resistant virus isolates) towards
      different drugs and substances, but also to screen inhibitors of other stages of
      HIV-1 life cycle.

PMID- 25850305
TI  - [The intracellular localization of the regulatory proteins of the densovirus of
      German cockroach, Blattella germanica].
AB  - The intracellular localization of the regulatory proteins encoded by the genome
      of the densovirus of German cockroach was analyzed using western-blotting of
      nuclear and cytoplasmic extracts of the densovirus-infected passaging cells
      tissue culture BGE-2. Two of the three regulatory proteins, NS1 and NS3, were
      shown to possess mainly nuclear localization, while NS2 protein was distributed
      between the nucleus and cytoplasm. Data obtained provide new information
      necessary for prediction of the functions of densovirus regulatory proteins.
      Intracellular localization of NS3 protein was described for the densoviruses for
      the first time.

PMID- 25850306
TI  - [Spread of tropical malaria in the Republic of Tajikistan (1994-2008)].
AB  - Tropical malaria occurred in the Republic of Tajikistan in 1994 after 40-year
      absence and spread in 28 regions of Tajikistan and in 3 cities (Dushanbe, Kulyab,
      and Kurgan-Tyube), peaking in 2000 (831 cases). A total of 3585 cases of tropical
      malaria were notified in 602 foci during a 15-year period. Migrants imported the
      pathogenic agent by the route of Pakistan-Afghanistan-Tajikistan during armed
      conflicts and in trading activities continually.The emergence of Asian Plasmodium
      falciparum phenotypes was accompanied by the clinical complications of the
      disease: the high percentage of moderate and severe forms of the disease was
      observed in preschool children in the absence of fatal outcomes. The rising
      incidence of malaria was associated with not only with the intensive import of
      the infection and the flight of infected malaria mosquitoes, but also with the
      active examination of the population during homestead rounds and with the timely
      laboratory diagnosis of malaria pathogens. The long-term goal antimalarial
      measures in the Republic of Tajikistan in 2009 resulted in the pause in the local
      transmission of tropical malaria, which meant its elimination in the country.

PMID- 25850307
TI  - [Achievement of the elimination of tropical malaria in The Republic of
      Tajikistan].
AB  - To achieve the elimination of tropical malaria, Tajikistan divided its territory
      into districts in terms of the malariogenic potential (receptivity +
      vulnerability) and identified priority regions to be exposed, determined the
      population's fever background and the required personnel, equipment, and reagents
      for parasitological examinations, and compiled an inventory of malaria foci. The
      investigators tested a new (artesunate + sulfadoxine-pyrimethamine) treatment
      regimen in patients with tropical malaria and in parasite carriers and
      established active detection of malaria cases through homestead rounds and
      population examinations. The packages of antimalarial measures were improved, by
      annually evaluating their efficiency in accordance with the monitoring and
      estimation indicators.

PMID- 25850308
TI  - [Behavioral features of the imago of malaria mosquitoes (Diptera, Culicidae,
      Anopheles) in uzbekistan].
AB  - Morphological, cytogenetic, and molecular genetic analyses made in the Fergana,
      Chirchik-Akhangaran, Mirzachul, and Zarafshan physicogeographical districts of
      Uzbekistan revealed the closely related species An. artemievi malaria mosquito
      from the An. maculipennis complex. In the human settlements and natural biotopes
      under their canopy of 7 physicogeographical districts of Uzbekistan, there were 6
      Anopheles mosquito species (An. artemievi, An. claviger, An. hyrcanus,
      An.martinius, An. pulcherrimus, and An. superpictus); An. superpictus is a
      dominant species in the human settlements and An. artemievi in subdominant.
      An.pulcherrimus was dominant and An. superpictus was subdominant under natural
      canopy conditions. The latter is of widespread occurrence in the mountain and
      piedmont areas of Uzbekistan. It is encountered in all the physicogeographical
      districts. An. artemievi is distributed in the river valleys in the Fergana,
      Chirchik-Akhangaran, Mirzachul, and Zarafshan physicogeographical districts. An.
      pulcherrimus is common in the plain river valleys, except in the Qashqadaryo
      physicogeographical district. An. martinius is found in the Qashqadaryo and
      Nizhneamudryo physicogeographical districts. Livestock houses are the most
      attractive day's rests for mosquitoes; utility rooms rank next in mosquito
      density. Housing premises are slightly occupied by mosquitoes. The maximum size
      of aggressive mosquitoes is noted in July, August, and early September.

PMID- 25850309
TI  - [The spatial distribution and infection of Culex pipiens L. mosquitoes with
      Western Nile virus in the Volgograd region].
AB  - The infection of Culex pipiens f. pipiens and Cx. pipiens f. molestus mosquitoes
      with Western Nile virus was studied. Their taxonomic status was determined from
      the type of mitochondrial DNA. Among 424 females individually examined, there
      were 4 infected specimens: 3 pipens females gathered in the urban and suburban
      open biotopes and one molestus female caught in the open urban biotope. Molestus
      mitotype females were first detected in the suburban open biotopes. The possible
      reasons for the wide colonization of molestus mosquitoes and its epidemic
      consequences are discussed.

PMID- 25850310
TI  - [Organization and epidemiological surveillance of Western Nile fever in case of
      the Volgograd Region].
AB  - Western Nile fever (WNF) is an arboviral infection of the most relevance to the
      Volgograd Region. The observed decreasing incidence of WNF in 2001-2006, 2008,
      and 2009 and a decline in the number of its severe forms are only suggestive of
      the temporary regression of the epidemic process in the Volgograd Region. There
      are prerequisites and forerunners for a complication of the epidemiological
      Western Nile fever situation in the Volgograd Region. The goal of the
      epidemiological survey of Western Nile fever is to provide necessary and
      sufficient information for the analysis of the epidemiological situation and to
      define a line of public health policy and actions when making managerial
      decisions.

PMID- 25850311
TI  - [Fleas of small mammals involved in the epizootic process in the Gorno-Altaisk
      natural focus of plague].

PMID- 25850312
TI  - [Pyrethroid resistance in human lice (Anoplura, Pediculidae): toxicological and
      molecular genetic methods].
AB  - The paper gives the data obtained in toxicological experiments versus analysis by
      a real-time polymerase chain reaction assay in permethrin-resistant human lice
      (VSSC1 gene kdr mutations leading to the amino acid replacements T9171 and L920F
      have been found). It is shown that the results of toxicological experiments may
      be indirectly indicative of the genetic composition of a study sample of lice.

PMID- 25850313
TI  - [Pneumocystosis as a nosocomial infection].

PMID- 25850314
TI  - [Comparative efficacy of original oil escazole and nemozole suspensions in albino
      mice with experimental trichinosis in the muscle phase of invasion].
AB  - The efficacy of original oil escazole and nemozole suspensions in albino mice in
      the muscle phase of T. spiralis invasion, which was detected by lifetime
      diagnosis of experimental trichinosis 6 days after initiation of treatment in a
      daily dose of 0.3 g/kg, was 100%. Under equal experimental conditions, the oil
      nemozole suspension showed high toxicity and caused death in 50% of the treated
      animals.

PMID- 25850315
TI  - [Novel bromine-containing salicylanilides (the compounds MST-36 and MST-38).
      Preparation and antihymenolepic activity].

PMID- 25850316
TI  - [Evaluation of the antihymenolepic activity of a number of chlorinated and
      brominated salicylanilide derivatives].

PMID- 25850317
TI  - [Immunochemical properties of the excretory-secretory antigen of Trichinella
      spiralis].
AB  - In vitro cultivation of Trichinella spiralis provided data on the structure of
      somatic and excretory-secretory antigens of T. spiralis larvae, their
      immunochemical properties were studied. The findings suggest that work should be
      continued to produce monoclonal antibodies and to develop highly sensitive and
      specific ELISA test systems for the diagnosis of human and animal trichinosis.

PMID- 25850318
TI  - [New evidence for the spread of Thelazia callipaeda in the Far East].
AB  - Thelazia callipaeda nematodes parasitize in the eyes of domestic and wild
      carnivorous mammals (more often in Canidae). Numerous cases of human infestation
      are also known. The nematode spreads in South and East Asia although in the last
      decade this has been reported from dogs, cats and wolves in South and Central
      Europe as well. In the Russian Federation, T. callipaeda was earlier observed in
      dogs, cats, foxes and raccoon dogs in some regions of the Russian Far East. Two
      cases of human infestation were also reported. There has been no evidence of T.
      callipaeda in Russia in the past 50 years. Postmortem parasitological surveys of
      various wild carnivores were performed in the Primorsky Territory of Russia in
      the winter of 2012 to the summer of 2014. Conjunctival sac including the space
      under the nictitating membrane was sought for nematodes. T. callipaeda was
      detected in 28 sables of the 492 examined ones, in 5 out of the 11 raccoon dogs,
      in 2 out of the 3 foxes, and in one lynx. The examination of 25 kolinskies, 4
      American minks, 3 Amur leopard cats, 2 yellow-throated martens and one badger
      provided negative results. The sable and the wild lynx are firstly reported as
      hosts of T. callipaeda. The findings suggest that there is a persisting natural
      reservoir of zoonotic thelaziosis in the Russian Far East. The epidemiological
      importance of this fact should not be underestimated.

PMID- 25850319
TI  - [Optimization of a model evaluating the efficiency of methods for sanitary
      helminthological examination of soil for its contamination with parasites].

PMID- 25850320
TI  - [Novel rapid method for examination of soil for helminth eggs].

PMID- 25850321
TI  - [A case of anisakidosis associated with Blastocyst invasion].

PMID- 25850322
TI  - [The network model is an effective form of training preventive medicine
      physicians (in case of medical parasitologists)].
AB  - Professional medical education is most cost-based when training highly skilled
      personnel. This is associated with expensive material and technical resources and
      a high labor-to-output ratio of practicing programs. The network model makes it
      possible to blaze new trails to achieve the quality of training the staff and the
      governmental support of its educational programs strengthens the coordination
      between higher educational establishments, research organizations, and
      professional learning communities. By using the training of medical
      parasitologists as an example, the paper shows a network model how to implement
      the educational program.

PMID- 25850323
TI  - [Methodical features of the molding of diagnostic competences in medical
      parasitology workers].
AB  - The paper provides a rationale for a procedure to mold diagnostic competences in
      medical workers of the laboratories of therapeutic-and-prophylactic institutions
      and hygiene and epidemiology centers, Russian Federal Service for Supervision of
      Consumer Rights Protection and Human Welfare. The methodical features of molding
      diagnostic competences in the above contingents are the design and organization
      of an educational process by applying systems integration and competence-based
      approaches; increased active self-directed learning of audience; a procedure to
      organize its unsupervised extracurricular activities. Professional habits and
      skills in laboratory specialists should be molded on the basis of didactic
      principles and in compliance with the found methodical patterns. The eventual
      result (molded competences) and its compliance with the practical health care
      requirements is assessed using all control types (incoming, running,
      intermediate, and ultimate ones). This ensures the stability and predictability
      of molding diagnostic competences in parasitology specialists.

PMID- 25850324
TI  - [The draft new World Health Organization program "global technical strategy for
      malaria control and elimination for 2016-2025"].

PMID- 25850325
TI  - The pathogenesis of atherosclerosis: a critical evaluation of the evidence.
AB  - The consistent topography, transmural involvement, and variation in severity and
      rate of progression in individual atherosclerotic lesions collectively indicate
      the dominant, primary role of hemodynamics. Specific anatomic configurations,
      vessels with elevated pressure, high velocity, or disturbed flow and iatrogenic
      production of accelerated atherosclerosis and its complications in therapeutic
      venous bypass grafts and arteriovenous shunts point to this role. The morphology
      and complications are consistent with the loss of cohesion and tensile strength
      of mural constituents and irreconcilably different from those of cholesterol- or
      fat-overfed animals and from other metabolic lipid storage disorders. These
      observations preclude dietary and circulating humoral factors and negate
      currently prevailing etiologic hypotheses that do not account for topography,
      pathogenesis, or complications. Atherosclerosis is the response to
      hemodynamically induced repetitive tensile stresses due to the pulse pressure and
      lesser flow-generated vibrations resulting in bioengineering fatigue occasioned
      by cumulative molecular fragmentation of mural constituents. This phenomenon also
      accounts for free-radical formation and lipoperoxidation. Atherosclerosis thus
      constitutes the combined manifestations of tissue fatigue and compensatory
      repair. When fatigue predominates, mural failure leads to the development of the
      primary complications (mural tears, dissection, ectasia, tortuosity, aneurysms).
      Lipid accumulation and thromboembolism are secondary phenomena. Fatigue onset is
      enhanced by hypertension and acquired or inherited defects of individual mural
      constituents. Iatrogenic and experimental production of atherosclerosis, its
      pathogenesis, and complications by hemodynamic means provides the ultimate proof
      of the causal role of bioengineering fatigue. 

PMID- 25850326
TI  - Pulmonary artery rupture as a complication of pulmonary hypertension: report of a
      case and review of the literature.
AB  - A 57-year-old woman with severe thromboembolic pulmonary hypertension died
      suddenly, approximately 3 hours after pulmonary angiography. Autopsy revealed a
      hemopericardium (350 mL) due to rupture of the pulmonary artery. Three acute
      partial intimal-medial tears also were observed. Fatal rupture of the mediastinal
      pulmonary arteries is a rare complication of severe pulmonary hypertension. A
      review of eight similar cases indicates that rupture tends to occur in patients
      with systemic levels of pressure, thrombotic (rather than plexogenic) forms of
      pulmonary hypertension, and survival longer than two years (mean, 4.5 years) from
      diagnosis. 

PMID- 25850327
TI  - Trypanosoma cruzi Infection Induces Myocardial Nitric Oxide Synthase.
AB  - Chagas' disease caused by Trypanosoma cruzi, is an important cause of myocarditis
      and cardiomyopathy. Acute and chronic infection is associated with myocardial
      dysfunction, including dysrhythmias, conduction disturbances, and congestive
      heart failure. Nitric oxide (NO) has been implicated in the myocardial
      dysfunction associated with diseases of the myocardium. The inducible form of
      nitric oxide synthase (iNOS) mediates the synthesis of NO and L-citrulline from L
      arginine. An abundance of iNOS mRNA by Northern blot and a marked expression of
      iNOS protein by Western blot was demonstrated in the myocardium of mice 30 days
      postinfection with the Brazil strain of T. cruzi. Immunocytochemical staining of
      the myocardial sections from infected mice also revealed the expression of iNOS.
      Consistent with these observations, the myocardial L-citrulline content was
      higher in infected mice, confirming NO expression in vivo. In addition, Northern
      blot analysis revealed that interleukin-1beta (IL-1beta) and tumor necrosis
      factor-alpha (TNF-alpha) mRNA were induced during infection. These data suggest
      that the myocardial cytokine-iNOS pathway may be an important factor in the
      pathogenesis of chagasic heart disease. In addition, this pathway may be a
      potential target of future pharmacologic intervention. 

PMID- 25850328
TI  - Cardiac valve interstitial cells: regulator of valve structure and function.
AB  - Cardiac valve interstitial cell tissue is present throughout the valve. The
      molecular biology of this cell type is not well known. The purpose of this review
      is to present our current understanding of the structure and function of valvular
      interstitial cells and to describe experimental approaches available to study the
      structure and regulation of interstitial cell function and the interaction of
      interstitial cells with the valve matrix and with the surface endocardial
      endothelial cells. Data available to date suggest that valvular interstitial
      cells are contractile, have some of the characteristic features of smooth-muscle
      cells, communicate with each other, secrete valvular matrix, regulate repair
      processes following valve injury, and exhibit heterogeneous phenotypes. Further
      studies are required to understand the regulation of structure and function of
      these cells in both health and disease. This information will indeed be useful in
      preventing valvular disease, in improving the design of therapeutic surgical
      valve reconstruction, and in designing prosthetic valves. 

PMID- 25850329
TI  - Kawasaki disease: sudden death in early infancy from accelerated late sequelae of
      coronary artery aneurysms.
AB  - Kawasaki disease is an acute, self-limited illness of young children (most
      commonly under 4 years of age) that may result in significant cardiovascular
      sequelae in about 20% of the patients 10 to 20 years later, mostly from occlusive
      coronary artery disease and myocardial infarction. Early mortality occurs in
      about 2% of children under the age of 2 years as the result of acute coronary
      vasculitis, with or without myocarditis, and of complications from coronary
      aneurysms. To our knowledge, fatal late sequelae of "healed" or "regressed"
      coronary aneurysms with occlusive intimal fibrocellular proliferation occurring
      in children under 1 year of age, have not been reported. We describe one such
      rare example in an 11-month-old infant. 

PMID- 25850330
TI  - Eye Movements Reveal the Influence of Event Structure on Reading Behavior.
AB  - When we read narrative texts such as novels and newspaper articles, we segment
      information presented in such texts into discrete events, with distinct
      boundaries between those events. But do our eyes reflect this event structure
      while reading? This study examines whether eye movements during the reading of
      discourse reveal how readers respond online to event structure. Participants read
      narrative passages as we monitored their eye movements. Several measures revealed
      that event structure predicted eye movements. In two experiments, we found that
      both early and overall reading times were longer for event boundaries. We also
      found that regressive saccades were more likely to land on event boundaries, but
      that readers were less likely to regress out of an event boundary. Experiment 2
      also demonstrated that tracking event structure carries a working memory load.
      Eye movements provide a rich set of online data to test the cognitive reality of
      event segmentation during reading. 

PMID- 25850331
TI  - Standard short-term diet ameliorates the lipid profile altered by a fructose-rich
      diet in rats.
AB  - Markers of metabolic abnormalities are commonly found in rodents fed a fructose
      rich diet. The purpose of this study was to determine whether the administration
      of a short-term standard diet to rats is able to improve the lipid profile
      altered by a fructose-rich diet. The male pups, immediately after birth, were
      divided in three groups according to the diet for 90 days. Standard diet: a
      standard diet for the whole experimental period; fructose (60% fructose-rich
      diet): fructose-rich diet during the entire experimental period;
      fructose/standard (FS): fructose-rich diet from the neonatal period up to 60 days
      of age and standard diet from 60 to 90 days of age. A fructose-rich diet from the
      neonatal period to 60 days reduced weight gain (P<0.05), as well as the weight of
      adipose tissues in all the regions analyzed (epididymal, mesenteric,
      retroperitoneal and posterior subcutaneous), and it altered the lipid profile
      (elevation of triglycerides, total cholesterol, low density lipoprotein (LDL)
      cholesterol and very low density lipoprotein (VLDL) cholesterol; P<0.05). When a
      standard diet was administered after the fructose-rich diet, it was able to
      partially reverse changes to the lipid profile, as total cholesterol levels were
      significantly different in all the groups (P<0.05), and triglyceride and VLDL
      cholesterol levels were similar between the control and FS group. In summary, a
      fructose-rich diet altered the lipid profile, and a standard diet can partially
      reverse the changed parameters in short term. 

PMID- 25850332
TI  - Regional cortical atrophy in depression and neurocognitive disorders.

PMID- 25850333
TI  - Changed in translation: mRNA recoding by -1 programmed ribosomal frameshifting.
AB  - Programmed -1 ribosomal frameshifting (-1PRF) is an mRNA recoding event commonly
      utilized by viruses and bacteria to increase the information content of their
      genomes. Recent results have implicated -1PRF in quality control of mRNA and DNA
      stability in eukaryotes. Biophysical experiments demonstrated that the ribosome
      changes the reading frame while attempting to move over a slippery sequence of
      the mRNA--when a roadblock formed by a folded downstream segment in the mRNA
      stalls the ribosome in a metastable conformational state. The efficiency of -1PRF
      is modulated not only by cis-regulatory elements in the mRNA but also by trans
      acting factors such as proteins, miRNAs, and antibiotics. These recent results
      suggest a molecular mechanism and new important cellular roles for -1PRF.

PMID- 25850334
TI  - A focus on the biosynthesis and composition of cuticle in fruits.
AB  - Cuticles are plant structures, composed mostly by lipidic layers, synthesized by
      nonwoody aerial plant organs and deposited on the surface of outer epidermal cell
      walls. Although its significance has been often disregarded, cuticle deposition
      modifies organ chemistry, influences mechanical properties, and plays a central
      role in sensing and interacting with the surrounding environment. Even though
      some research has been undertaken addressing cuticle biosynthesis and composition
      in vegetative plant tissues, comparatively less information is available
      regarding cuticle composition in the epidermis of fruits. However, recent work
      points to a role for cuticles in the modulation of fruit quality and postharvest
      performance, indicating that current models for the investigation of fruit
      development, metabolism, and quality need to integrate a comprehensive knowledge
      of the cuticle layer. This paper provides an overview of recent findings and
      observations regarding cuticle biosynthesis and composition in fruits from
      species of agronomic and economic relevance. Important, but often neglected
      differences in cuticle composition and biosynthesis patterns among diverse fruit
      species are described herein to generate an atlas of what is currently known
      about fruit cuticles and to highlight what remains to be explored. Emphasis is
      placed on the need to investigate each genetic background considering its own
      specificities, to permit correlations with the particular physiology of each
      species considered. Both specific composition and changes during maturation and
      ripening are reviewed. 

PMID- 25850335
TI  - Feasibility of smartphone diaries and personal dosimeters to quantitatively study
      exposure to ultraviolet radiation in a small national sample.
AB  - BACKGROUND: In 2007, a national skin cancer prevention campaign was launched to
      reduce the UV exposure of the Danish population. To improve campaign evaluation a
      questionnaire validation using UV-dosimeters was initiated. AIM: To show the
      feasibility of dosimeters for national representative studies and of smartphones
      as a data collection tool. MATERIALS AND METHODS: Participants were sent a
      dosimeter which they wore for 7 days, received a short diary questionnaire by
      text message each day and subsequently a longer questionnaire. Correlation
      between responses from questionnaire, smartphone diaries and dosimeters were
      examined. RESULTS: This study shows a 99.5% return rate (n = 205) of the
      dosimeters by ordinary mail and high response-rates for a smartphone
      questionnaire dairy. Correlation coefficients for outdoor-time reported through
      smartphones and dosimeters as average by week 0.62 (0.39-0.77), P < 0.001 (n =
      40). Correlation coefficient for outdoor time estimated by questionnaire and
      dosimeters were 0.42 (0.11-0.64), P = 0.008. The subjective perception of the
      weather was the only covariate significantly influencing questionnaire estimates
      of actual outdoor exposure. We showed that dosimeter studies are feasible in
      national settings and that smartphones are a useful tool for monitoring and
      collecting UV behavior data. CONCLUSION: We found diary data reported on a daily
      basis through smartphones more strongly associated with actual outdoor time than
      questionnaire data. Our results demonstrate tools and possible considerations for
      executing a UV behavior questionnaire validation.

PMID- 25850336
TI  - The loleva oral and written language test: psychometric properties.
AB  - LolEva, a computerized test for ages 3 to 8 years old, identifies issues in the
      development of skills that can lead to reading acquisition difficulties. Its
      structure captures two distinct areas: Phonological Awareness (PA, seven
      subtests: rhyme, identification-addition-omission of syllable and phoneme at the
      beginning and end of a word), and Initial Reading Competence (IRC, six subtests:
      reading uppercase and lowercase letters, simple words, complex words, and
      pseudowords, and word segmentation). With results collected in a sample of 341
      children with the target ages and attending public or private schools, the alpha
      coefficient was .94 for PA, and .92 for IRC. Factor analysis indicated three
      factors are present (performance on PA and IRC, and word reading times), together
      explaining 75% of variance, providing evidence to support the construct validity
      of the test. On the other hand, analysis of variance showed significant
      differences for year-in-school variable for PA subscale, F(4, 336) = 191.385, p <
      .001, eta2 p = .695, 1-beta = 1.0, as well as for IRC subscale, both in number of
      correct answers, which increased as schooling progressed: F(4, 336) = 197.897, p
      < .001, eta2 p = .702, 1-beta = 1.0, and task completion time, which decreased as
      education progressed: F(4, 335) = 47.048, p < .001, eta2 p = .360, 1-beta = 1.0.
      Also, PA repeated measures analysis revealed that was easier Identification than
      Addition and Omission , F(2, 672) = 31.639, p < .001, eta2 p = .086, 1-beta =
      1.0, syllable-related tasks than phoneme-related task, F(1, 336) = 229.000, p <
      .001, eta2 p = .405, 1-beta = 1.0, and syllable or phoneme at the end of the word
      than at the beginning, F(1, 336) = 59.201, p < .001, eta2 p = .150, 1-beta = 1.0.
      Moreover, all items were examined and indexes of difficulty and discrimination
      were obtained. 

PMID- 25850337
TI  - Serial measurements of serum thyroglobulin in response to recombinant human
      thyrotropin stimulation.

PMID- 25850338
TI  - Neuropsychological performance in treatment-seeking Operation Enduring
      Freedom/Operation Iraqi Freedom Veterans with a history of mild traumatic brain
      injury.
AB  - INTRODUCTION: Clinical neuropsychological presentation of treatment-seeking
      Veterans with a remote history of mild traumatic brain injury (mTBI) is widely
      variable. This manuscript seeks to better characterize cognitive concerns in the
      post-acute phase following mTBI and to identify the neuropsychological profiles
      of a large sample of clinically referred Operation Enduring Freedom/Operation
      Iraqi Freedom/Operation New Dawn (OEF/OIF/OND) Veterans with a history of mTBI
      and current cognitive complaints. We hypothesized that a minority of cases would
      exhibit valid and widespread neuropsychological deficits. METHOD: Retrospective
      chart reviews of neuropsychological testing and mental health symptoms and
      diagnoses were conducted on 411 clinically referred OEF/OIF/OND Veterans with a
      history of mTBI. Groups were created based on scores on performance validity
      measures and based on overall neuropsychological performance. RESULTS: A total of
      29.9% of the sample performed below normative expectations on at least one
      performance validity test (PVT). Of those Veterans performing adequately on PVTs,
      60% performed within normal limits on virtually all neuropsychological measures
      administered, leaving only 40% performing below expectations on two or more
      measures. Mood and neurobehavioral symptoms were significantly elevated in
      Veterans performing below cutoff on PVTs compared to Veterans who performed
      within normative expectations or those with valid deficits. Neurobehavioral
      symptoms were significantly correlated with mental health symptom reports but not
      with injury variables. CONCLUSIONS: In summary, in a large sample of clinically
      referred Veterans with persistent cognitive complaints after mild TBI, a third
      demonstrated invalid clinical neuropsychological testing, and, of those
      performing at or above cutoff on PVTs, over half performed within normative
      expectations across most neuropsychological tests administered. Results highlight
      the importance of objective assessment of cognitive functioning in this
      population as subjective reports do not correspond to objective assessment in the
      majority of cases.

PMID- 25850339
TI  - Relative contributions of the major human CYP450 to the metabolism of icotinib
      and its implication in prediction of drug-drug interaction between icotinib and
      CYP3A4 inhibitors/inducers using physiologically based pharmacokinetic modeling.
AB  - OBJECTIVE: Icotinib is an anticancer drug, but relative contributions of CYP450
      have not been identified. This study was carried out to identify the contribution
      percentage of CYP450 to icotinib and use the results to develop a physiologically
      based pharmacokinetic (PBPK) model, which can help to predict drug-drug
      interaction (DDI). METHODS: Human liver microsome (HLM) and supersome using
      relative activity factor (RAF) were employed to determine the relative
      contributions of the major human P450 to the net hepatic metabolism of icotinib.
      These values were introduced to develop a PBPK model using SimCYP. The model was
      validated by the observed data in a Phase I clinical trial in Chinese healthy
      subjects. Finally, the model was used to simulate the DDI with ketoconazole or
      rifampin. RESULTS: Final contribution of CYP450 isoforms determined by HLM showed
      that CYP3A4 provided major contributions to the metabolism of icotinib. The
      percentage contributions of the P450 to the net hepatic metabolism of icotinib
      were determined by HLM inhibition assay and RAF. The AUC ratio under concomitant
      use of ketoconazole and rifampin was 3.22 and 0.55, respectively. CONCLUSION:
      Percentage of contribution of CYP450 to icotinib metabolism was calculated by
      RAF. The model has been proven to fit the observed data and is used in predicting
      icotinib-ketoconazole/rifampin interaction.

PMID- 25850340
TI  - Anti-proliferative effect of Fe(III) complexed with 1-(2-hydroxy-3
      methoxybenzaldehyde)-4-aminosalicylhydrazone in HepG2 cells.
AB  - We previously developed a chelating ligand, 1-(2-hydroxy-3-methoxybenzaldehyde)-4
      aminosalicylhydrazone (HMB-ASH), which can chelate Fe(III) to form a complex. The
      HMB-ASH-Fe(III) complex exhibits a dose-dependent anti-proliferative effect in
      HepG2 cells, whereas the ligand, HMB-ASH, and Fe(III) alone had no considerable
      effect. The HMB-ASH-Fe(III) complex was composed of Fe(III):HMB-ASH (1:2), as
      determined by high-performance liquid chromatography with high-resolution mass
      spectrometry. The IC50 value was approximately 20 MUM, which was comparable to
      those of the anti-cancer drugs oxaliplatin (OXP) and etoposide (ETP) under the
      same conditions. Similar to OXP and ETP, HMB-ASH-Fe(III) induced apoptosis in
      HepG2 cells, as revealed by terminal deoxynucleotidyl transferase fluorescein-12
      dUTP nick end labeling assay. 

PMID- 25850341
TI  - Association of overexpression of efflux pump genes with antibiotic resistance in
      Pseudomonas aeruginosa strains clinically isolated from urinary tract infection
      patients.
AB  - There are several mechanisms for antibiotic-resistant Pseudomonas aeruginosa. The
      purpose of this study is to investigate the association between the expression of
      efflux pump-coding genes and antibiotic resistance in P. aeruginosa causing
      urinary tract infections (UTIs). We extracted the RNA from 105 clinical strains
      of P. aeruginosa isolated from UTI patients with full data on antibiotic MICs and
      assayed real-time quantitative reverse-transcription PCR. We investigated the
      gene expressions of four resistance nodulation cell division-type multi-drug
      efflux pump systems (MexAB-OprM, MexCD-OprJ, MexEF-OprN and MexXY(-OprA)) and the
      correlation of the MICs of nine antibiotics, risk factors and antibiotic
      resistance-related genes with expressions of mexB, mexC, mexE and mexY.
      Multivariate statistical data demonstrated a significant relationship between
      increased expression of mexB or mexC and complicated UTI (Odds ratio=8.03,
      P<0.001 and Odds ratio=8.86, P=0.032, respectively). We also found a significant
      association between the increased expression of mexC and resistance to
      levofloxacin (LVFX) (Odds ratio=4.48, P=0.035). In conclusion, increased
      expression of mexC leads to LVFX resistance in P. aeruginosa causing UTI. These
      results contribute to our knowledge of the efflux pump system and antibiotic
      resistance. 

PMID- 25850342
TI  - Antimicrobial resistance surveillance of doripenem in China.
AB  - To investigate the antibacterial resistance to doripenem in China and to
      understand the distribution trends of resistant bacteria. All the clinical
      isolates were collected from hospitals and the susceptibility tests were
      performed using the agar dilution method recommended by the Clinical Laboratory
      Standards Institute (CLSI) central laboratory. The susceptibility of the isolates
      to antimicrobial agents was determined using the CLSI (2014) or European
      Committee on Antimicrobial Susceptibility Testing (EUCAST) (2013) guidelines. A
      total of 4047 pathogenic strains were isolated from 18 tertiary hospitals in 18
      cities across China between July 2011 and June 2012. MIC results indicated that
      the vast majority of Enterobacteriaceae maintained high susceptibility to
      doripenem, with a lower resistance rate (1.9%) than that observed for other drugs
      tested. In the case of non-fermenting Gram-negative isolates, the resistance rate
      of Pseudomonas aeruginosa was 16.2%, which was less than that of imipenem and
      meropenem, and the Acinetobacter baumannii doripenem resistance rate was 67.4%.
      Doripenem also showed good in vitro activity against other the bacteria tested.
      This study suggests that the gradual increase in carbapenem nonsusceptible
      Enterobacteriaceae should be monitored carefully alongside the increasing
      multidrug-resistant and extensively drug-resistant A. baumannii. 

PMID- 25850344
TI  - Liver myeloid-derived suppressor cells expand in response to liver metastases in
      mice and inhibit the anti-tumor efficacy of anti-CEA CAR-T.
AB  - Chimeric antigen receptor-modified T cell (CAR-T) technology, a promising
      immunotherapeutic tool, has not been applied specifically to treat liver
      metastases (LM). While CAR-T delivery to LM can be optimized by regional
      intrahepatic infusion, we propose that liver CD11b+Gr-1+ myeloid-derived
      suppressor cells (L-MDSC) will inhibit the efficacy of CAR-T in the intrahepatic
      space. We studied anti-CEA CAR-T in a murine model of CEA+ LM and identified
      mechanisms through which L-MDSC expand and inhibit CAR-T function. We established
      CEA+ LM in mice and studied purified L-MDSC and responses to treatment with
      intrahepatic anti-CEA CAR-T infusions. L-MDSC expanded threefold in response to
      LM, and their expansion was dependent on GM-CSF, which was produced by tumor
      cells. L-MDSC utilized PD-L1 to suppress anti-tumor responses through engagement
      of PD-1 on CAR-T. GM-CSF, in cooperation with STAT3, promoted L-MDSC PD-L1
      expression. CAR-T efficacy was rescued when mice received CAR-T in combination
      with MDSC depletion, GM-CSF neutralization to prevent MDSC expansion, or PD-L1
      blockade. As L-MDSC suppressed anti-CEA CAR-T, infusion of anti-CEA CAR-T in
      tandem with agents targeting L-MDSC is a rational strategy for future clinical
      trials. 

PMID- 25850345
TI  - Advances in hepatology: 2015.

PMID- 25850343
TI  - My 65 years in protein chemistry.
AB  - This is a tour of a physical chemist through 65 years of protein chemistry from
      the time when emphasis was placed on the determination of the size and shape of
      the protein molecule as a colloidal particle, with an early breakthrough by James
      Sumner, followed by Linus Pauling and Fred Sanger, that a protein was a real
      molecule, albeit a macromolecule. It deals with the recognition of the nature and
      importance of hydrogen bonds and hydrophobic interactions in determining the
      structure, properties, and biological function of proteins until the present
      acquisition of an understanding of the structure, thermodynamics, and folding
      pathways from a linear array of amino acids to a biological entity. Along the
      way, with a combination of experiment and theoretical interpretation, a mechanism
      was elucidated for the thrombin-induced conversion of fibrinogen to a fibrin
      blood clot and for the oxidative-folding pathways of ribonuclease A. Before the
      atomic structure of a protein molecule was determined by x-ray diffraction or
      nuclear magnetic resonance spectroscopy, experimental studies of the fundamental
      interactions underlying protein structure led to several distance constraints
      which motivated the theoretical approach to determine protein structure, and
      culminated in the Empirical Conformational Energy Program for Peptides (ECEPP),
      an all-atom force field, with which the structures of fibrous collagen-like
      proteins and the 46-residue globular staphylococcal protein A were determined. To
      undertake the study of larger globular proteins, a physics-based coarse-grained
      UNited-RESidue (UNRES) force field was developed, and applied to the protein
      folding problem in terms of structure, thermodynamics, dynamics, and folding
      pathways. Initially, single-chain and, ultimately, multiple-chain proteins were
      examined, and the methodology was extended to protein-protein interactions and to
      nucleic acids and to protein-nucleic acid interactions. The ultimate results led
      to an understanding of a variety of biological processes underlying natural and
      disease phenomena. 

PMID- 25850347
TI  - Current management of acute liver failure.
AB  - PURPOSE OF REVIEW: Acute liver failure (ALF) is a rare but life-threatening
      systemic disorder. Survival rates with or without emergency liver transplantation
      (ELT) are increasing. The benefit of ELT in some cases has been questioned and
      the potential for survival with medical management alone is changing our approach
      to the management of this disease. RECENT FINDINGS: Survival rates for all causes
      of ALF are increasing because of improvements in the care of the critically ill
      patient. A multifactorial approach involving support of respiratory, circulatory
      and renal function together with measures to avoid intracranial hypertension,
      metabolic disequilibrium and sepsis are required. For those who do not respond to
      these measures or specific antidotes, the selection methods for those likely to
      benefit from transplantation remain imperfect and novel methods based on the
      prediction of hepatic regeneration are required. For patients with ALF secondary
      to acetaminophen overdose, some experts believe a randomized controlled trial is
      required to find those most likely to benefit from ELT. SUMMARY: ALF remains a
      life-threatening condition with a high mortality rate requiring prompt support of
      multiorgan failure. Historical listing criteria for ELT are being questioned and
      improvement in medical management offers the option of continued improvements in
      transplant-free survival.

PMID- 25850346
TI  - Aging and liver disease.
AB  - PURPOSE OF REVIEW: Aging is a condition in which a person gradually loses the
      ability to maintain homeostasis, due to structural alteration or dysfunction.
      Aging is a major risk factor for most chronic diseases. As the liver has a
      remarkable ability to regenerate, this review assessed the effect of aging on
      clinical liver disease with references to preclinical models when relevant to
      pathogenesis. RECENT FINDINGS: Aging has been shown to not only enhance
      vulnerability to acute liver injury but also increase susceptibility of the
      fibrotic response. Aging is associated with the severity and poor prognosis of
      various liver diseases including nonalcoholic fatty liver disease, alcoholic
      liver disease, hepatitis C, and liver transplantation. SUMMARY: Treatment of
      older patients with liver disease may require different or longer interventions.
      Transplantation of an older liver will be less tolerant of subsequent injury.
      Future studies are needed to understand more about the molecular mechanism of
      aging and contribute to the development of a noble treatment strategy that can
      block the progression of aging-induced liver diseases.

PMID- 25850348
TI  - Human pluripotent stem cell-derived cholangiocytes: current status and future
      applications.
AB  - PURPOSE OF REVIEW: Pluripotent stem cells, such as embryonic stem cells and
      inducible pluripotent stem (iPS) cells, have high proliferative multipotency for
      differentiation into mature functional cells that are useful for treatment and
      basic research on several diseases. Cholangiocytes are differentiated from fetal
      hepatic progenitor cells (hepatoblasts) and are important for transport of bile
      acids that are synthesized by mature hepatocytes in the liver. However, the
      molecular mechanisms of development and function of human cholangiocytes remain
      unknown. This review mentions the potential of human cholangiocytic culture from
      pluripotent stem cells to contribute to the analyses of the human bile duct
      system and diseases. RECENT FINDINGS: Recent studies found that human hepatic
      cholangiocytic cells can be differentiated from human embryonic stem and iPS
      cells in a suitable culture condition. Cholangiocytic cysts have epithelial cell
      polarity formed in a three-dimensional cell culture system using extracellular
      matrices. SUMMARY: Disease pathogenesis was elucidated in vitro using
      differentiated cells from disease-related iPS cells. Using genome-editing
      enzymes, iPS cells with disease-specific gene mutations can be easily and rapidly
      established. These disease-related iPS cells and cholangiocytic culture system
      may be useful for analyses and drug screening of human bile duct diseases.

PMID- 25850353
TI  - Compound heterozygous C282Y/Q283P and Q283P/H63D mutations in haemochromatosis.

PMID- 25850350
TI  - Mild cognitive impairment is associated with poorer decision-making in community
      based older persons.
AB  - OBJECTIVE: To test the hypothesis that mild cognitive impairment (MCI) is
      associated with poorer financial and healthcare decision-making. DESIGN:
      Community-based epidemiological cohort study. SETTING: Communities throughout
      northeastern Illinois. PARTICIPANTS: Older persons without dementia from the Rush
      Memory and Aging Project (N = 730). MEASUREMENTS: All participants underwent a
      detailed clinical evaluation and decision-making assessment using a measure that
      closely approximates materials used in real-world financial and healthcare
      settings. This allowed for measurement of total decision-making and financial and
      healthcare decision-making. Regression models were used to examine whether MCI
      was associated with a lower level of decision-making. In subsequent analyses, the
      relationship between specific cognitive systems (episodic memory, semantic
      memory, working memory, perceptual speed, visuospatial ability) and decision
      making was explored in participants with MCI. RESULTS: MCI was associated with
      lower total, financial, and healthcare decision-making scores after accounting
      for the effects of age, education, and sex. The effect of MCI on total decision
      making was equivalent to the effect of more than 10 additional years of age.
      Additional models showed that, when considering multiple cognitive systems,
      perceptual speed accounted for the most variance in decision-making in
      participants with MCI. CONCLUSION: Persons with MCI may have poorer financial and
      healthcare decision-making in real-world situations, and perceptual speed may be
      an important contributor to poorer decision-making in persons with MCI.

PMID- 25850355
TI  - The collision tumor in the assessment of non-melanoma skin cancer caused by
      occupational UV exposure.

PMID- 25850354
TI  - Influences of hormone replacement therapy on olfactory and cognitive function in
      postmenopausal women.
AB  - Olfactory dysfunction can be an early sign of Alzheimer's disease. Since hormone
      replacement therapy (HRT) may protect against Alzheimer's disease in
      postmenopausal women, the question arises as to whether it also protects against
      olfactory dysfunction in such women. A total of three olfactory and 12
      neurocognitive tests were administered to 432 healthy postmenopausal women with
      varied HRT histories. Serum levels of reproductive hormones were obtained for all
      subjects; APOE-epsilon4 haplotype was determined for 77 women. National Adult
      Reading Test and Odor Memory/Discrimination Test scores were positively
      influenced by HRT. Odor Identification and Odor Memory/Discrimination Test scores
      were lower for women who scored poorly on a delayed recall test, a surrogate for
      mild cognitive impairment. The Wechsler Adult Intelligence Scale, Revised, as a
      Neuropsychological Instrument Spatial Span Backwards Test scores were higher in
      women receiving estrogen and progestin HRT and directly correlated with serum
      testosterone levels, the latter implying a positive effect of testosterone on
      spatial memory. APOE-epsilon4 was associated with poorer odor threshold test
      scores. These data suggest that HRT positively influences a limited number of
      olfactory and cognitive measures during menopause.

PMID- 25850356
TI  - Neoflavonoid dalbergiphenol from heartwood of Dalbergia sissoo acts as bone
      savior in an estrogen withdrawal model for osteoporosis.
AB  - OBJECTIVE: Dalbergiphenol (DGP) is a neoflavonoid isolated from heartwood of
      Dalbergia sissoo. Effects of DGP on skeletal health remain to be elucidated. The
      objective of the present study was to investigate the biological effects of DGP
      on bone loss in ovariectomized mice. METHODS: Adult BALB/c mice were
      ovariectomized and administered DGP (1 and 5  mg/kg/d) or 17beta-estradiol (E2)
      orally for 6 weeks. The sham group and the ovariectomy (OVX) + vehicle group
      served as controls. Eight female BALB/c mice were taken for each group. Uterine
      estrogenicity, bone microarchitecture, biomechanical strength, new bone formation
      (based on bone formation rate and mineral apposition rate), and skeletal
      expression of osteogenic and resorptive gene markers were studied. RESULTS: OVX
      resulted in a marked increase in body weight and a decrease in femoral and
      vertebral trabecular bone volume that were prevented by DGP or E2 treatment. DGP
      treatment increased bone biomechanical strength and new bone formation rate in
      ovariectomized mice, comparable with E2 treatment. However, increase in uterine
      weight and estrogenicity were observed in E2-treated ovariectomized mice, but not
      in response to DGP treatment. Treatment with DGP increased messenger RNA
      expression of runt-related transcription factor 2, osterix, and collagen type I,
      and decreased messenger RNA expression of tartrate-resistant acid phosphatase and
      the osteoprotegerin-to-receptor activator of nuclear factor-kappaB ligand ratio
      in the femur of ovariectomized mice. CONCLUSIONS: Overall findings suggest that
      DGP treatment can effectively prevent OVX-induced increase in bone loss and
      decrease in bone strength possibly by increasing osteoblastic activities and by
      decreasing osteoclastic activities.

PMID- 25850357
TI  - Failure to treat menopausal symptoms: a disconnect between clinical practice and
      scientific data.

PMID- 25850358
TI  - A facile and efficient synthesis of polystyrene/gold-platinum composite particles
      and their application for aerobic oxidation of alcohols in water.
AB  - Herein we develop a facile and effective method for the synthesis of composite
      particles composed of polystyrene microspheres decorated with gold-platinum alloy
      nanoparticles, which exhibited excellent catalytic activity and recyclability for
      1-phenylethanol oxidation under mild conditions (without a base, air as an
      oxidant, in water, at 40  degrees C). 

PMID- 25850359
TI  - Diffusion Tensor Imaging Adds Diagnostic Accuracy in Magnetic Resonance
      Neurography.
AB  - OBJECTIVE: The aim of this study was to determine whether quantitative diffusion
      tensor imaging (DTI) adds diagnostic accuracy in magnetic resonance neurography.
      MATERIALS AND METHODS: This prospective study was approved by the institutional
      review board. We enrolled 16 patients with peripheral polyneuropathy of various
      etiologies involving the upper arm and 30 healthy controls. Magnetic resonance
      neurography was performed at 3 T using transverse T2-weighted (T2-w) turbo spin
      echo and spin echo planar imaging diffusion-weighted sequences. T2-weighted
      normalized signal (nT2), fractional anisotropy (FA), apparent diffusion
      coefficient (ADC), radial diffusivity (RD), and axial diffusivity (AD) of the
      median, ulnar, and radial nerves were quantified after manual segmentation.
      Diagnostic performance of each separate parameter and combinations of parameters
      was assessed using the area under the receiver operating characteristic curve
      (AUC). Bootstrap validation was used to adjust for potential overfitting.
      RESULTS: Average nT2, ADC, RD, and AD values of the median, ulnar, and radial
      nerve were significantly increased in neuropathy patients compared with that in
      healthy controls (nT2, 1.49 +/- 0.05 vs 1.05 +/- 0.05; ADC, 1.4 * 10(-3) +/- 2.8
      * 10(-5) mm(2)/s vs 1.1 * 10(-3) +/- 1.3 * 10(-5) mm(2)/s; RD, 9.5 * 10(-4) +/-
      2.9 * 10(-5) mm(2)/s vs 7.2 * 10(-4) +/- 1.3 * 10(-5) mm(2)/s; AD, 2.3 * 10(-3)
      +/- 3.7 * 10(-5) mm(2)/s vs 2.0 * 10(-3) +/- 2.2 * 10(-5) mm(2)/s; P < 0.001 for
      all comparisons). Fractional anisotropy values were significantly decreased in
      patients (0.51 +/- 0.01 vs 0.59 +/- 0.01; P < 0.001). T2-weighted normalized
      signal and DTI parameters had comparable diagnostic accuracy (adjusted AUC: T2-w,
      0.92; FA, 0.88; ADC, 0.89; AD, 0.84; RD, 0.86). Combining DTI parameters
      significantly improved the diagnostic accuracy over single-parameter analysis. In
      addition, the combination of nT2 with DTI parameters yielded excellent adjusted
      AUCs up to 0.97 (nT2 + FA). CONCLUSIONS: Diffusion tensor imaging has high
      diagnostic accuracy in peripheral neuropathy. Combining DTI with T2 can
      outperform T2-w imaging alone and provides added value in magnetic resonance
      neurography.

PMID- 25850360
TI  - The effect of bladder sensation on uroflowmetry parameters in healthy young men.
AB  - AIMS: To investigate the effect of the bladder sensation grade on uroflowmetry
      parameters. METHODS: Fifty healthy volunteering young men were enrolled in the
      present study. In total, three uroflowmetry evaluations were made. Qmax , Qave ,
      VV, and PVR urine was obtained three times in three described bladder sensation
      grades, nearly at the same time of the day. RESULTS: The mean age of the
      participants in the present study is 29.08 +/- 3.8 years. The mean Qmax values of
      the volunteers were 17.4 +/- 4.8 ml/s, 24.1 +/- 6.0 ml/s, and 29.6 +/- 6.5 ml/s
      in the first, second, and third, voiding desire grades, respectively. The mean
      Qave values were 9.9 +/- 2.1 ml/s, 12.9 +/- 2.9 ml/s, and 15.9 +/- 4.0 ml/s for
      each of the voiding desire grades mentioned. A statistically significant
      difference was obvious for all three bladder sensation grades in terms of Qmax
      and Qave values (P = 0.000). However, no statistically significant difference was
      seen regarding the PVR urine volumes. The mean voided volume in the first, second
      and third uroflowmetry were 140 +/- 42 ml, 245 +/- 64 ml, and 449 +/- 105 ml,
      respectively. The highest Qmax and Qave values were obtained when the desire to
      void was urgent. CONCLUSIONS: The findings of the study show that, uroflowmetry
      evaluations are to be made if the patients have a strong desire to void. Only
      thus the highest Qmax values can be obtained; yet, the degree of perceived
      bladder sensation does not have a statistically significant impact on PVR
      quantity. Neurourol. Urodynam. 35:622-624, 2016. (c) 2015 Wiley Periodicals, Inc.

PMID- 25850361
TI  - Transitions in the communication experiences of tracheostomised patients in
      intensive care: a qualitative descriptive study.
AB  - AIMS AND OBJECTIVES: To describe how tracheostomised patients in intensive care
      experience acts of communication and to better understand their experiences in
      the context of the transitions theory. BACKGROUND: Waking up in an intensive care
      unit unable to speak because of mechanical ventilation can be challenging.
      Communication aids are available, but patients still report difficulties
      communicating. Investigating how mechanically ventilated patients experience
      communication in the context of the transitions theory might elucidate new ways
      of supporting them during their transitions while being ventilated. DESIGN: A
      qualitative, descriptive design. METHODS: Eleven patients who had previously been
      tracheostomised in an intensive care unit were included in this quality
      improvement project conducted in a university hospital in Norway. Participants
      were tracheostomised from 3-27 days. Semistructured interviews were conducted
      from June 2013-August 2013, 3-18 months after hospital discharge. Transcripts
      were analysed using inductive content analysis. RESULTS: Participants reported a
      great diversity of emotions and experiences attempting to communicate while being
      tracheostomised. One overarching theme emerging from the analysis was the
      'Experience of caring and understanding despite having uncomfortable feelings due
      to troublesome communication.' The theme consists of three categories. The
      category 'Emotionally challenging' shows that patients struggled initially. With
      time, their coping improved, as revealed in the category 'The experience changes
      with time.' Despite difficulties, participants described positive experiences, as
      shown in the category 'Successful communication.' CONCLUSION: The importance of
      patients experiencing caring and understanding despite their difficult situation
      constitutes the core finding. The findings suggest that participants went through
      different transitions. Some reached the end of their transition, experiencing
      increased stability. RELEVANCE TO CLINICAL PRACTICE: Despite challenges with
      communication, participants reported that caring and safety provided by health
      care professionals were significant experiences. They viewed nonverbal
      communication as being very important.

PMID- 25850363
TI  - President's report.

PMID- 25850362
TI  - Recovery of Ventriculo-Atrial Conduction after Adrenaline in Patients Implanted
      with Pacemakers.
AB  - BACKGROUND: Ventriculo-atrial (VA) conduction can have negative consequences for
      patients with implanted pacemakers and defibrillators. There is concern whether
      impaired VA conduction could recover during stressful situations. Although the
      influence of isoproterenol and atropine are well established, the effect of
      adrenaline has not been studied systematically. The objective of this study was
      to determine if adrenaline can facilitate recovery of VA conduction in patients
      implanted with pacemakers. METHODS: A prospective study was conducted on 61
      consecutive patients during a 4-month period (April-July 2014). The presence of
      VA conduction was assessed during the pacemaker implantation procedure. In case
      of an impaired VA conduction, adrenaline infusio was used as a stress surrogate
      to test conduction recovery. RESULTS: The indications for pacemaker implantation
      were: sinus node dysfunction in 18 patients, atrioventricular (AV) block in 40
      patients, binodal dysfunction (sinus node+ AV node) in two patients and other
      (carotid sinus syndrome) in one patient. In the basal state, 15/61 (24.6%)
      presented spontaneous VA conduction and 46/61 (75.4%) had no VA conduction. After
      administration of adrenaline, there was VA conduction recovery in 5/46 (10.9%)
      patients. CONCLUSIONS: Adrenaline infusion produced recovery of VA conduction in
      10.9% of patients with absent VA conduction in a basal state. Recovery of VA
      conduction during physiological or pathological stresses could be responsible for
      the pacemaker syndrome, PMT episodes, or certain implantable cardiac
      defibrillator detection issues.

PMID- 25850364
TI  - Should retention of a tooth be an important goal of dentistry? How do you decide
      whether to retain and restore a tooth requiring endodontic treatment or to
      extract and if possible replace the tooth?
AB  - Whether a questionable tooth should be treated endodontically or extracted, is
      still a dilemma clinicians encounter every day. With advances in technology such
      as implantology, deciding whether or not to save a tooth is still not clear.
      Local site-specific factors and patient-related factors that may affect the
      longevity of a particular tooth should be considered in preparing the treatment
      plan. Long-term success rates for root canal therapy and implant-supported crowns
      demonstrate similar outcomes. A choice between these alone is not sufficient in
      the decision-making process. Only following a systematic evaluation of the
      reasons for and against tooth retention as directed by each individual case, can
      the best option be decided.

PMID- 25850368
TI  - Associate professor Giampiero Rossi-Fedele.

PMID- 25850369
TI  - A novel set of microsatellite markers for the European Grapevine Moth Lobesia
      botrana isolated using next-generation sequencing and their utility for genetic
      characterization of populations from Europe and the Middle East.
AB  - Using a high-throughput 454 pyrosequencing approach a novel set of microsatellite
      markers was developed for one of the key grapevine insect pests, the European
      grapevine moth Lobesia botrana (Lepidoptera: Tortricidae). 20 primer pairs
      flanking a microsatellite motif were designed based on the sequences obtained and
      were subsequently evaluated in a sample of 14 L. botrana populations from Europe
      and the Middle East. 11 markers showed stable and reproducible amplification
      patterns; however, one of the 11 markers was monomorphic in all L. botrana
      populations analysed. Estimated frequencies of null alleles of more than 20% were
      evident for two of the markers tested, but varied substantially depending on the
      respective L. botrana population. In 12 of the 14 L. botrana populations observed
      heterozygosities were lower to those expected under Hardy-Weinberg equilibrium,
      indicating a deficiency of heterozygotes in the respective populations. The
      overall F ST value of 0.075 suggested a moderate but significant genetic
      differentiation between the L. botrana populations included in this study. In
      addition, a clear geographic structure was detected in the set of samples,
      evident through a significant isolation by distance and through results from
      structure analysis. In structure analysis, L. botrana populations were grouped in
      two clearly separated clusters according to their European (Spain, Italy,
      Germany) or Middle Eastern (Israel, Syria, Turkey) origin. This novel set of
      microsatellite markers can now be applied to study the evolutionary ecology of
      this species including host shifts and host adaptation as well as spread of
      individuals across worldwide viticulture. 

PMID- 25850370
TI  - A single high-resolution HLA mismatch has a similar adverse impact on the outcome
      of related hematopoietic stem cell transplantation as a single low-resolution HLA
      mismatch.
AB  - The relative importance of the resolution level of HLA typing has not been fully
      defined for related donor transplantation. To address this question, we
      retrospectively evaluated patients who underwent a first related hematopoietic
      stem cell transplantation (HSCT) from 2000 to 2011 from an HLA high-resolution
      matched (MRD, n = 2,244), high-resolution 1 locus-mismatched (HR-MMRD, n = 116),
      or low-resolution 1 locus-mismatched related donor (LR-MMRD, n = 396) in the
      graft-versus-host direction at three loci (HLA A, B, and DRB1) using the database
      of the Japan Society for Hematopoietic Cell Transplantation. The median age was
      40 years (0-74). The median follow-up duration of surviving patients was 950
      days. Although the cumulative incidences of grade III-IV acute graft-versus-host
      disease (GVHD) in the HR-MMRD and LR-MMRD groups were significantly higher than
      those in the MRD group (HR-MMRD 19.8%, LR-MMRD 20.4%, and MRD 9.5%), there was no
      statistically significant difference between the HR-MMRD and LR-MMRD groups (P =
      0.65). Although both HR-MMRD and LR-MMRD were significantly associated with an
      increased risk of non-relapse mortality and a worse overall survival, there was
      no statistically significant difference between the HR-MMRD and LR-MMRD groups.
      In conclusion, LR-MM and HR-MM have a similar adverse impact on the outcome in
      related HSCT.

PMID- 25850371
TI  - Regional versus urban differences in teenage alcohol use: Does parental
      disapproval account for these differences?
AB  - OBJECTIVE: To investigate if parental disapproval of alcohol use accounts for
      differences in adolescent alcohol use across regional and urban communities.
      DESIGN: Secondary data analysis of grade-level stratified data from a random
      sample of schools. SETTING: High schools in Victoria, Australia. PARTICIPANTS: A
      random sample of 10 273 adolescents from Grade 7 (mean age = 12.51 years), 9
      (14.46 years) and 11 (16.42 years). MAIN OUTCOME MEASURES: The key independent
      variables were parental disapproval of adolescent alcohol use and regionality
      (regional/ urban), and the dependent variable was past 30 days alcohol use.
      RESULTS: After adjusting for potential confounders, adolescents in regional areas
      were more likely to use alcohol in the past 30 days (OR = 1.83, 1.44 and 1.37 for
      Grades 7, 9 and 11, respectively, P < 0.05), and their parents have a lower level
      of disapproval of their alcohol use (b = -0.12, -0.15 and -0.19 for Grades 7, 9
      and 11, respectively, P < 0.001). Bootstrapping analyses suggested that 8.37%,
      23.30% and 39.22% of the effect of regionality on adolescent alcohol use was
      mediated by parental disapproval of alcohol use for Grades 7, 9 and 11
      participants respectively (P < 0.05). CONCLUSIONS: Adolescents in urban areas had
      a lower risk of alcohol use compared with their regional counterparts, and
      differences in parental disapproval of alcohol use contributed to this
      difference.

PMID- 25850372
TI  - Droplet digital polymerase chain reaction (PCR) outperforms real-time PCR in the
      detection of environmental DNA from an invasive fish species.
AB  - Environmental DNA (eDNA) has been used to investigate species distributions in
      aquatic ecosystems. Most of these studies use real-time polymerase chain reaction
      (PCR) to detect eDNA in water; however, PCR amplification is often inhibited by
      the presence of organic and inorganic matter. In droplet digital PCR (ddPCR), the
      sample is partitioned into thousands of nanoliter droplets, and PCR inhibition
      may be reduced by the detection of the end-point of PCR amplification in each
      droplet, independent of the amplification efficiency. In addition, real-time PCR
      reagents can affect PCR amplification and consequently alter detection rates. We
      compared the effectiveness of ddPCR and real-time PCR using two different PCR
      reagents for the detection of the eDNA from invasive bluegill sunfish, Lepomis
      macrochirus, in ponds. We found that ddPCR had higher detection rates of bluegill
      eDNA in pond water than real-time PCR with either of the PCR reagents, especially
      at low DNA concentrations. Limits of DNA detection, which were tested by spiking
      the bluegill DNA to DNA extracts from the ponds containing natural inhibitors,
      found that ddPCR had higher detection rate than real-time PCR. Our results
      suggest that ddPCR is more resistant to the presence of PCR inhibitors in field
      samples than real-time PCR. Thus, ddPCR outperforms real-time PCR methods for
      detecting eDNA to document species distributions in natural habitats, especially
      in habitats with high concentrations of PCR inhibitors. 

PMID- 25850373
TI  - Contributions of spinal D-amino acid oxidase to chronic morphine-induced
      hyperalgesia.
AB  - Spinal D-amino acid oxidase (DAAO) is an FAD-dependent peroxisomal flavoenzyme
      which mediates the conversion of neutral and polar D-amino acids (including D
      serine) to the corresponding alpha-keto acids, and simultaneously produces
      hydrogen peroxide and ammonia. This study has aimed to explore the potential
      contributions of spinal DAAO and its mediated hydrogen peroxide/D-serine
      metabolism to the development of morphine-induced hyperalgesia. Bi-daily
      subcutaneous injections of morphine to mice over 7 days induced thermal
      hyperalgesia as measured by both the hot-plate and tail-immersion tests, and
      spinal astroglial activation with increased spinal gene expression of DAAO, glial
      fibrillary acidic protein (GFAP) and pro-inflammatory cytokines (interleukin
      1beta (IL-1beta), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF
      alpha)). Subcutaneous injections of the potent DAAO inhibitor CBIO (5-chloro
      benzo[D]isoxazol-3-ol) prevented and reversed the chronic morphine-induced
      hyperalgesia. CBIO also inhibited both astrocyte activation and the expression of
      pro-inflammatory cytokines. Intrathecal injection of the hydrogen peroxide
      scavenger PBN (phenyl-N-tert-butylnitrone) and of catalase completely reversed
      established morphine hyperalgesia, whereas subcutaneous injections of exogenous D
      serine failed to alter chronic morphine-induced hyperalgesia. These results
      provided evidence that spinal DAAO and its subsequent production of hydrogen
      peroxide rather than the D-serine metabolism contributed to the development of
      morphine-induced hyperalgesia.

PMID- 25850374
TI  - A direct qPCR method for residual DNA quantification in monoclonal antibody drugs
      produced in CHO cells.
AB  - Chinese hamster ovary (CHO) cells are the host cell of choice for manufacturing
      of monoclonal antibody (mAb) drugs in the biopharmaceutical industry. Host cell
      DNA is an impurity of such manufacturing process and must be controlled and
      monitored in order to ensure drug purity and safety. A conventional method for
      quantification of host residual DNA in drug requires extraction of DNA from the
      mAb drug substance with subsequent quantification of the extracted DNA using real
      time PCR (qPCR). Here we report a method where the DNA extraction step is
      eliminated prior to qPCR. In this method, which we have named 'direct resDNA
      qPCR', the mAb drug substance is digested with a protease called KAPA in a 96
      well PCR plate, the protease in the digest is then denatured at high temperature,
      qPCR reagents are added to the resultant reaction wells in the plate along with
      standards and controls in other wells of the same plate, and the plate subjected
      to qPCR for analysis of residual host DNA in the samples. This direct resDNA qPCR
      method for CHO is sensitive to 5.0fg of DNA with high precision and accuracy and
      has a wide linear range of determination. The method has been successfully tested
      with four mAbs drug, two IgG1 and two IgG4. Both the purified drug substance as
      well as a number of process intermediate samples, e.g., bioreactor harvest,
      Protein A column eluate and ion-exchange column eluates were tested. This method
      simplifies the residual DNA quantification protocol, reduces time of analysis and
      leads to increased assay sensitivity and development of automated high-throughput
      methods.

PMID- 25850375
TI  - Somitogenesis: From somite to skeletal muscle.
AB  - Myogenesis is controlled by an elaborate system of extrinsic and intrinsic
      regulatory mechanisms in all development stages. The aim of this review is to
      provide an overview of the different stages of myogenesis and muscle
      differentiation in mammals, starting from somitogenesis and analysis of the
      different portions that constitute the mature somite. Particular attention was
      paid to regulatory genes, in addition to mesodermal stem cells, which represent
      the earliest elements of myogenesis. Finally, the crucial role of growth factors,
      molecules of vital importance in contractile regulation, hormones and their
      function in skeletal muscle differentiation, growth and metabolism, and the role
      played by central nervous system, are discussed. 

PMID- 25850377
TI  - New Dimeric and seco-Abietane Diterpenoids from Salvia wardii.
AB  - Two dimeric abietane diterpenoids, salviwardins A and B (1 and 2), and a seco
      abietane diterpenoid salviwardin C (3), along with five known analogues (4-8),
      were isolated from the roots of Salvia wardii. The structures of these isolates
      were elucidated by extensive spectroscopic methods. The inhibitory activities of
      these isolates against five human cancer cell lines in vitro were also tested.

PMID- 25850378
TI  - New Diterpenes from Cultures of the Fungus Engleromyces goetzii and Their CETP
      Inhibitory Activity.
AB  - One new cleistanthane-type diterpene named engleromycenolic acid A (1), one new
      rosane-type diterpene named engleromycenolic acid B (2) and one new natural
      rosane-type diterpene, engleromycenol (3), along with three known rosane-type
      diterpenes, rosololactone (4), rosenonolactone (5) and 7-deoxyrosenonolactone (6)
      were isolated from cultures of the fungus Engleromyces goetzii, where it
      naturally grows on Alpine bamboo culms. The new compounds were elucidated based
      on their spectroscopic data. In addition, compounds 1-6 were evaluated for their
      cholesterol ester transfer protein (CETP) inhibition activity. This paper reports
      the isolation, structural elucidation, and CETP inhibition activity of these
      compounds.

PMID- 25850380
TI  - Interaction between anti-Alzheimer and antipsychotic drugs in modulating
      extrapyramidal motor disorders in mice.
AB  - Antipsychotics are often used in conjunction with anti-Alzheimer drugs to treat
      the behavioral and psychological symptoms of dementia (BPSD). Here, we examined
      the effects of cholinesterase inhibitors (ChEIs), donepezil and galantamine, on
      antipsychotic-induced extrapyramidal side effects (EPS) in mice. The effects of
      serotonergic agents on the EPS drug interaction were also evaluated. Donepezil
      (0.3-3 mg/kg) did not induce EPS signs by itself; however, it significantly
      potentiated bradykinesia induction with a low dose of haloperidol (0.5 mg/kg) in
      dose-dependent and synergistic manners. Galantamine (0.3-3 mg/kg) elicited mild
      bradykinesia at a high dose and dose-dependently augmented haloperidol-induced
      bradykinesia. The EPS potentiation by galantamine was blocked by trihexyphenidyl
      (a muscarinic antagonist), but not by mecamylamine (a nicotinic antagonist). In
      addition, the bradykinesia potentiation by galantamine was significantly reduced
      by (+/-)-8-hydroxy-2-(di-n-propylamino)-tetralin (a 5-HT1A agonist), ritanserin
      (a 5-HT2 antagonist), and SB-258585 (a 5-HT6 antagonist). The present results
      give us a caution for the antipsychotics and ChEIs interaction in inducing EPS in
      the treatment of BPSD. In addition, second generation antipsychotics, which can
      stimulate 5-HT1A receptors or antagonize 5-HT2 and 5-HT6 receptors, seem to be
      favorable as an adjunctive therapy for BPSD. 

PMID- 25850381
TI  - Nicorandil directly and cyclic GMP-dependently opens K+ channels in human bypass
      grafts.
AB  - As we previously demonstrated the role of different K(+) channels in the action
      of nicorandil on human saphenous vein (HSV) and human internal mammary artery
      (HIMA), this study aimed to analyse the contribution of the cGMP pathway in
      nicorandil-induced vasorelaxation and to determine the involvement of cGMP in the
      K(+) channel-activating effect of nicorandil. An inhibitor of soluble guanylate
      cyclase (GC), ODQ, significantly inhibited nicorandil-induced relaxation, while
      ODQ plus glibenclamide, a selective ATP-sensitive K(+) (KATP) channel inhibitor,
      produced a further inhibition of both vessels. In HSV, ODQ in combination with 4
      aminopyridine, a blocker of voltage-gated K(+) (KV) channels, did not modify the
      concentration-response to nicorandil compared with ODQ, whereas in HIMA, ODQ plus
      iberiotoxin, a selective blocker of large-conductance Ca(2+)-activated K(+)
      (BKCa) channels, produced greater inhibition than ODQ alone. We showed that the
      cGMP pathway plays a significant role in the vasorelaxant effect of nicorandil on
      HSV and HIMA. It seems that nicorandil directly opens KATP channels in both
      vessels and BKCa channels in HIMA, although it is possible that stimulation of GC
      contributes to KATP channels activation in HIMA. Contrary, the activation of KV
      channels in HSV is probably due to GC activation and increased levels of cGMP. 

PMID- 25850382
TI  - Biochemistry students' ideas about how an enzyme interacts with a substrate.
AB  - Enzyme-substrate interactions are a fundamental concept of biochemistry that is
      built upon throughout multiple biochemistry courses. Central to understanding
      enzyme-substrate interactions is specific knowledge of exactly how an enzyme and
      substrate interact. Within this narrower topic, students must understand the
      various binding sites on an enzyme and be able to reason from simplistic lock and
      key or induced fit models to the more complex energetics model of transition
      state theory. Learning to understand these many facets of enzyme-substrate
      interactions and reasoning from multiple models present challenges where students
      incorrectly make connections between concepts or make no connection at all. This
      study investigated biochemistry students' understanding of enzyme-substrate
      interactions through the use of clinical interviews and a national administration
      (N = 707) of the Enzyme-Substrate Interactions Concept Inventory. Findings
      include misconceptions regarding the nature of enzyme-substrate interactions,
      naive ideas about the active site, a lack of energetically driven interactions,
      and an incomplete understanding of the specificity pocket.

PMID- 25850383
TI  - Effect of electroconvulsive seizures on pattern separation.
AB  - Strategies employing different techniques to inhibit or stimulate neurogenesis
      have implicated a role for adult-born neurons in the therapeutic effect of
      antidepressant drugs, as well as a role in memory formation. Electroconvulsive
      seizures (ECS), an animal model of electroconvulsive therapy, robustly stimulate
      hippocampal neurogenesis, but it is not known how this relates to either
      therapeutic efficacy or unwanted cognitive side effects. We hypothesized that the
      ECS-derived increase in adult-born neurons would manifest in improved pattern
      separation ability, a memory function that is believed to be both hippocampus
      dependent and coupled to neurogenesis. To test this hypothesis, we stimulated
      neurogenesis in adult rats by treating them with a series of ECS and compared
      their performances in a trial-unique delayed nonmatching-to-location task (TUNL)
      to a control group. TUNL performance was analyzed over a 12-week period, during
      which newly formed neurons differentiate and become functionally integrated in
      the hippocampal neurocircuitry. Task difficulty was manipulated by modifying the
      delay between sample and choice, and by varying the spatial similarity between
      target and distracter location. Although animals learned the task and improved
      the number of correct responses over time, ECS did not influence spatial pattern
      separation ability.

PMID- 25850385
TI  - Reflections on New York City's 1947 Smallpox Vaccination Program and Its 1976
      Swine Influenza Immunization Program.
AB  - In 1947, a smallpox outbreak occurred in New York City with a total of twelve
      cases and two deaths. In order to contain this outbreak, the New York City
      Department of Health launched a mass immunization campaign that over a period of
      some 60 days vaccinated 6.35 million people. This article examines in detail the
      epidemiology of this outbreak and the measures employed to contain it. In 1976, a
      swine influenza strain was isolated among a few recruits at a US Army training
      camp at Fort Dix, New Jersey. It was concluded at the time that this virus
      possibly represented a re-appearance of the 1918 influenza pandemic influenza
      strain. As a result, a mass national immunization program was launched by the
      federal government. From its inception, the program encountered a myriad of
      challenges ranging from doubts that it was even necessary to the development of
      Guillain-Barre paralysis among some vaccine recipients. This paper examines the
      planning for and implementation of the swine flu immunization program in New York
      City. It also compares it to the smallpox vaccination program of 1947. Despite
      equivalent financial and personnel resources, leadership and organizational
      skills, the 1976 program only immunized approximately a tenth of the number of
      New York City residents vaccinated in 1947. The reasons for these marked
      differences in outcomes are discussed in detail.

PMID- 25850386
TI  - A Randomized Trial to Compare Alternative Educational Interventions to Increase
      Colorectal Cancer Screening in a Hard-to-Reach Urban Minority Population with
      Health Insurance.
AB  - This randomized controlled trial assessed different educational approaches for
      increasing colorectal cancer screening uptake in a sample of primarily non-US
      born urban minority individuals, over aged 50, with health insurance, and out of
      compliance with screening guidelines. In one group, participants were mailed
      printed educational material (n = 180); in a second, participants' primary care
      physicians received academic detailing to improve screening referral and follow
      up practices (n = 185); in a third, physicians received academic detailing and
      participants received tailored telephone education (n = 199). Overall, 21.5% of
      participants (n = 121) received appropriate screening within one year of
      randomization. There were no statistically significant pairwise differences
      between groups in screening rate. Among those 60 years of age or older, however,
      the detailing plus telephone education group had a higher screening rate than the
      print group (27.3 vs. 7.7%, p = .02). Different kinds of interventions will be
      required to increase colorectal cancer screening among the increasingly small
      population segment that remains unscreened. ClinicalTrials.gov Identifier:
      NCT02392143.

PMID- 25850388
TI  - Complications and neurological deficits following minimally invasive anterior
      column release for adult spinal deformity: a retrospective study.
AB  - BACKGROUND: Minimally invasive techniques have become increasing popular and are
      expanding into deformity surgery. The lateral retroperitoneal transpsoas anterior
      column release (ACR) is a newer minimally invasive alternative to posterior
      osteotomy techniques for correcting and promoting global spinal alignment. This
      procedure attempts to avoid the potential complications associated with
      conventional osteotomies, but has its own subset of unique complications to be
      discussed in depth. METHODS: A retrospective review was performed in all patients
      who underwent the minimally invasive (MIS) ACR procedure from 2010 to present at
      our institution. All perioperative and postoperative complications were recorded
      by an independent reviewer. Demographics, spinopelvic parameters, and operative
      data were collected. The primary etiologic diagnosis was adult spinal deformity.
      Spinopelvic parameters were measured based on standing 36-inch scoliosis films.
      RESULTS: Thirty-one patients underwent a total of 47 MIS-ACRs. The mean age of
      the cohort was 62. Mean follow up was 12 months (range 3-38 months). The average
      change from in lumbar lordosis (LL) was 17.6 degrees , in pelvic tilt was 4.3
      degrees , coronal Cobb was 13.9 and in SVA was 3.8 cm. Of the 47 MIS-ACR
      procedures, there were 9 (9/47, 19 %) major complications related to the ACR.
      Iliopsoas weakness was seen in eight patients and retrograde ejaculation in one
      patient. Only one patient remained with mild motor deficit at the most recent
      follow-up. No revision surgeries were required for the anterolateral approach.
      There was no vascular, visceral, or infectious complications associated with the
      MIS-ACR. CONCLUSION: The MIS-ACR is one of the most technically demanding
      procedures performed from the lateral transpsoas approach. This procedure has the
      advantage of maintaining and improving spinal global alignment while minimizing
      blood loss and excessive tissue dissection. It comes with its own unique set of
      potentially catastrophic complications and should only be performed by surgeons
      proficient in both deformity correction and the lateral approach.

PMID- 25850387
TI  - MIS lateral spine surgery: a systematic literature review of complications,
      outcomes, and economics.
AB  - BACKGROUND: Over the past decade, the minimally disruptive lateral transpsoas
      approach for lumbar interbody fusion (MI-LIF) is increasingly being used as an
      alternative to conventional surgical approaches. The purpose of this review was
      to evaluate four primary questions as they relate to MI-LIF: (1) Is there an
      anatomical justification for MI-LIF at L4-5? (2) What are the complication and
      outcome profiles of MI-LIF and are they acceptable with respect to conventional
      approaches? (3) Given technical and neuromonitoring differences between various
      MI-LIF procedures, are there any published clinical differences? And, (4) are
      modern minimally disruptive procedures (e.g., MI-LIF) economically viable?
      METHODS: Through a MEDLINE and Google Scholar search, a total of 237 articles
      that discussed MI-LIF were identified. Of those, topical areas included anatomy
      (22), biomechanics/testing (17), technical descriptions (11), case reports (40),
      complications (30), clinical and radiographic outcomes (43), deformity (23),
      trauma or thoracic applications (10), and review articles (41). RESULTS: In
      answer to the questions posed, (1) there is a high strength of evidence showing
      MI-LIF to be anatomically justified at all levels of the lumbar spine from L1-2
      to L4-5. The evidence also supports the use of advanced neuromonitoring
      modalities. (2) There is moderate strength evidence in support of reproducible
      and reasonable complication, side effect, and outcome profiles following MI-LIF
      which may be technique dependent. (3) There is low-strength evidence that shows
      elevated neural complication rates in non-traditional (e.g., shallow-docking
      approaches and/or those without specialized neuromonitoring) MI-LIF, and (4)
      there is low- to moderate-strength evidence that modern minimally disruptive
      surgical approaches are cost-effective. CONCLUSIONS: There is considerable
      published evidence to support MI-LIF in spinal fusion and advanced applications,
      though the results of some reports, especially concerning complications, vary
      greatly depending on technique and instrumentation used. Additional cost
      effectiveness analyses would assist in fully understanding the long-term
      implications of MI-LIF.

PMID- 25850390
TI  - Anterior cervical interbody fusion with the Zero-P spacer: mid-term results of
      two-level fusion.
AB  - PURPOSE: Our aim was to compare the safety and efficacy of anterior cervical
      discectomy and fusion (ACDF) using the Zero-P spacer versus the plate method in
      patients with cervical spine spondylosis. METHODS: Clinical and radiologic data
      from 69 patients undergoing two-level ACDF from January 2009 to May 2011 were
      collected prospectively. The Zero-P spacer was implanted in 37 patients (group A)
      and the anterior cervical plate and interbody cage in 32 (group B). Patients were
      followed for at least 3 years after surgery. Clinical outcomes were analyzed
      using the Neck Disability Index and Japanese Orthopaedic Association (JOA)
      scoring. The thickness of the prevertebral soft tissue at the fused levels was
      measured on the lateral cervical spine radiographs and dysphagia was assessed
      using the Bazaz score. Fusion rate, change in cervical lordosis, and adjacent
      segment degeneration were analyzed. RESULTS: Neurologic outcomes were
      statistically equivalent between the two groups. The incidence of postoperative
      dysphagia was significantly lower in group A than in group B at 2 and 6 months (p
      < 0.05). At the final follow-up, there were no significant differences in the C2
      C7 Cobb angles between the two groups (p > 0.05). Also, degenerative changes in
      adjacent segments occurred in five group A patients and seven group B patients (p
      = 0.361). There were no differences in fusion rate during the radiologic follow
      up. CONCLUSIONS: Clinical results with the Zero-P spacer used for two-level ACDF
      were satisfactory. The device is superior to the traditional plate for preventing
      postoperative dysphagia and avoiding possible complications associated with a
      plate. Prospective trials with more patients and longer follow-ups are required
      to confirm these observations.

PMID- 25850391
TI  - Risk factors for predicting cement leakage following percutaneous vertebroplasty
      for osteoporotic vertebral compression fractures.
AB  - PURPOSE: The purpose of the present study is to identify independent risk factors
      for the occurrence of cement leakage (CL) during percutaneous vertebroplasty
      (PVP) for four different leakage types in treating osteoporotic vertebral
      compression fractures (OVCFs). METHODS: We retrospectively reviewed 292 patients
      who underwent PVP for single-level OVCF from January 2009 to March 2011. The
      influences of several potential risk factors that might affect the occurrence of
      CL were assessed using univariate and multivariate analyses. Cement leakage was
      evaluated by computed tomography and classified into four different types:
      through the basivertebral vein (B-type), the segmental vein (S-type), a cortical
      defect (C-type), and intradiscal leakage (D-type). RESULTS: Cement leakage was
      found in 227 of the 292 treated vertebrae. None of the parameters showed a
      statistically significant effect by univariate analysis. However, multivariate
      analysis showed that cement viscosity was an independent risk factor in B-type
      CL, fracture severity and fracture type were in S-type CL, fracture severity and
      presence of cleft on MRI were in C-type CL, and fracture severity, cortical
      disruption on MRI, presence of cleft on MRI and cement viscosity were in D-type
      CL. CONCLUSION: Each different vertebral fracture pattern has its own risk
      factors for CL. Identification of the above predicting factors for CL
      preoperatively might be helpful for more rigorous and strict patient selection
      criteria for the appropriate candidates for PVP.

PMID- 25850392
TI  - Intervertebral disc degenerative changes after intradiscal injection of TNF-alpha
      in a porcine model.
AB  - PURPOSE: To investigate whether exogenous tumor necrosis factor-alpha (TNF-alpha)
      will initiate a degenerative process in intervertebral disc in vivo. METHODS:
      Exogenous TNF-alpha in dosages of 50 and 100 ng in 50 MUL Dulbecco's Modified
      Essential Medium (DMEM) was injected into porcine lumbar discs; a third disc was
      injected only with 50 MUL DMEM as a control. Magnetic resonance imaging (MRI)
      yielding T1- and T2-weighted images, T2-mapping, and post-contrast T1 images was
      performed and histology was studied as well. RESULTS: After 3 months, a
      significant decrease in T2 value calculated from T2-mapping MRI was observed in
      the annulus and nucleus of both groups injected with TNF-alpha along with a
      slight decrease in disc height and nucleus volumes in comparison to the control
      discs. No obvious visual differences among the groups were observed in the normal
      T1- and T2-weighted MRI images. Post-contrast T1 MRI showed increased annulus
      enhancement in both TNF-alpha-injected groups compared to the control discs,
      while no enhancement difference was observed in the nucleus. Histological
      analysis showed degenerative changes with annulus fissure, cell cluster, nucleus
      matrix loss, vascularization and interleukin-1beta expression in the outer
      annulus of both TNF-alpha-injected discs, while no degenerative changes were
      observed in the control discs. CONCLUSIONS: Intradiscal injection of exogenous
      TNF-alpha caused early stage disc degeneration in a porcine model. It may thus
      support the hypothesis of exogenic TNF-alpha being an important early
      pathogenetic factor in disc degeneration.

PMID- 25850394
TI  - Review of supplemental views and stress radiography in musculoskeletal trauma:
      upper extremity.
AB  - The standard radiographic series is not always sufficient to diagnose and
      characterize subtle musculoskeletal injuries. Missed or delayed diagnoses can
      negatively affect patient acute morbidity and long-term outcomes. Similarly,
      management based on erroneous diagnoses may lead to unnecessary treatment and
      restrictions. Body part or joint specific supplemental radiographic views and
      stress radiography offer an alternative for further evaluation of subtle injuries
      in specific clinical situations and may obviate the need for the added cost and
      potential ionizing radiation exposure of further cross-sectional imaging.
      Familiarity with these complementary exams allows radiologists to play an
      important role in patient care, as their utilization can improve diagnostic
      accuracy, clarify subtle or uncertain findings, and direct timely patient
      management. This review highlights important supplemental views and stress
      radiographic examinations useful in the evaluation of emergent upper extremity
      musculoskeletal trauma. 

PMID- 25850393
TI  - Reduced expression of miRNA-1237-3p associated with poor survival of spinal
      chordoma patients.
AB  - PURPOSE: Aberrant expression of miRNAs has been demonstrated to contribute to
      human carcinogenesis. This study was aimed at profiling differentially expressed
      miRNAs in formalin-fixed and paraffin-embedded tissues of spinal chordoma and
      testing the potential for using altered expression of miRNAs as prognostic
      markers for spinal chordoma patients. METHODS: A miRNA array was used to profile
      differentially expressed miRNAs in spinal chordoma and nucleus pulposus tissues.
      Four of these differentially expressed miRNAs was then validated in spinal
      chordoma and control patients using quantitative RT-PCR. Bioinformatical analysis
      identified potential GO terms and signaling pathways affected by these microRNAs.
      Altered miR-1237-3p expression was then found to be associated with
      clinicopathological characteristics and prognosis of spinal chordoma patients.
      RESULTS: The miRNA arrays identified 29 differentially expressed miRNAs in spinal
      chordoma tissues, four of which were verified by qRT-PCR in 42 spinal chordomas
      and 14 control tissues. Bioinformatical analysis revealed that the potential
      target genes of these miRNAs were mainly involved in gene transcription, cell
      junction proteins, and gene pathways in cancer and endocytosis. Reduced miR-1237
      3p expression was associated with tumor invasion and worse recurrence-free
      survival of spinal chordoma patients (chi (2) = 16.217, p = 0.000, log-rank
      test). Multivariate analyses showed that miR-1237-3p expression was an
      independent prognostic factor for patients with spinal chordoma (HR = 0.001, 95 %
      CI 0.000-0.136, p = 0.005). CONCLUSION: The data from the current study
      identified a total of 29 differentially expressed miRNAs in chordoma tissues and
      reduced miR-1237-3p expression was associated with chordoma invasion and worse
      recurrence-free survival of the patients.

PMID- 25850395
TI  - Predicting the potential distribution of the amphibian pathogen Batrachochytrium
      dendrobatidis in East and Southeast Asia.
AB  - Batrachochytrium dendrobatidis (Bd) is the pathogen responsible for
      chytridiomycosis, a disease that is associated with a worldwide amphibian
      population decline. In this study, we predicted the potential distribution of Bd
      in East and Southeast Asia based on limited occurrence data. Our goal was to
      design an effective survey area where efforts to detect the pathogen can be
      focused. We generated ecological niche models using the maximum-entropy approach,
      with alleviation of multicollinearity and spatial autocorrelation. We applied
      eigenvector-based spatial filters as independent variables, in addition to
      environmental variables, to resolve spatial autocorrelation, and compared the
      model's accuracy and the degree of spatial autocorrelation with those of a model
      estimated using only environmental variables. We were able to identify areas of
      high suitability for Bd with accuracy. Among the environmental variables, factors
      related to temperature and precipitation were more effective in predicting the
      potential distribution of Bd than factors related to land use and cover type. Our
      study successfully predicted the potential distribution of Bd in East and
      Southeast Asia. This information should now be used to prioritize survey areas
      and generate a surveillance program to detect the pathogen. 

PMID- 25850396
TI  - Evaluation of emamectin benzoate and substance EX against salmon lice in sea
      ranched Atlantic salmon smolts.
AB  - Experimental releases of Atlantic salmon smolts treated with emamectin benzoate
      (EB) against salmon lice have previously been used to estimate the significance
      of salmon lice on the survival of migrating smolts. In recent years, the salmon
      louse has developed reduced sensitivity to EB, which may influence the results of
      such release experiments. We therefore tested the use of 2 anti-lice drugs: EB
      was administered to salmon smolts in high doses by intra-peritoneal injection and
      the prophylactic substance EX (SubEX) was administered by bathing. A third,
      untreated control group was also established. Salmon were challenged with
      copepodids of 2 strains of salmon lice (1 EB-sensitive strain and 1 with reduced
      EB-sensitivity) in mixed-group experimental tanks. At 31 d post-challenge, the
      numbers of pre-adult lice on treated fish were around 20% compared with the
      control fish, with minor or no differences between the 2 treatments and lice
      strains. Both treatments therefore appeared to give the smolts a high degree of
      protection against infestation of copepodids of salmon lice. However,
      significantly lower growth of the EB-treatment group indicates that bathing the
      fish in SubEX is less stressful for smolts than intra-peritoneal injection of EB.

PMID- 25850397
TI  - Molecular and morphological evidence for the widespread distribution of Laticola
      paralatesi infecting wild and farmed Lates calcarifer in Australia.
AB  - Infections with monogeneans of the Diplectanidae can limit productivity of and
      cause considerable health issues for fish in aquaculture. To date, 9 species of
      diplectanids have been reported from the Asian sea bass or barramundi Lates
      calcarifer (Perciformes: Latidae) in the Asia-Pacific region. This study
      characterised the diplectanid parasite fauna found infecting wild and farmed
      barramundi from 5 localities in tropical Australia, including north Queensland
      and Western Australia. A combination of morphometric and comparative genetic
      analyses of partial 28S ribosomal RNA (28S rRNA) from specimens recovered were
      used to confirm their identity and to explore relationships with other
      diplectanids. These data revealed that a single, dominant species of diplectanid,
      Laticola paralatesi, infects wild and farmed Lates calcarifer in tropical
      Australia. Laticola lingaoensis Yang, Kritsky, Sun, Jiangying, Shi & Agrawal,
      2006 is synonymised with L. seabassi (Wu, Li, Zhu & Xie, 2005) Domingues &
      Boeger, 2008 based on the combination of the host infected (Lates calcarifer),
      geographic distribution, distinct morphological similarity, and identical 28S
      rRNA sequence data identified here. Laticola seabassi is now designated as the
      type species of Laticola due to nomenclatural priority. 

PMID- 25850398
TI  - Growth inhibition of Aeromonas salmonicida and Yersinia ruckeri by disinfectants
      containing peracetic acid.
AB  - Peracetic acid (PAA) is a therapeutic agent used for disinfection in aquaculture,
      but it must be investigated thoroughly in order to mitigate diseases without
      harming the fish. Successful disinfectants (like PAA) should not leave dangerous
      residues in the environment in order to successfully contribute to sustainable
      aquaculture. The aim of our study was to compare the effectiveness of 6
      commercial PAA products with different molecular PAA:H2O2 ratios to reduce
      bacterial growth of Aeromonas salmonicida and Yersinia ruckeri and to determine
      effective concentrations and exposure times. All products reduced colony-forming
      units (CFUs) of A. salmonicida and Y. ruckeri. Products with higher molecular
      PAA:H2O2 ratios inhibited growth better than products with lower molecular
      PAA:H2O2 ratios at the same PAA concentration; this indicates that H2O2 is not
      the driving force in the reduction of A. salmonicida and Y. ruckeri growth by PAA
      in vitro. The practical application of the products with high molecular PAA:H2O2
      ratios should be prioritized if these pathogens are diagnosed. 

PMID- 25850399
TI  - Monoclonal antibody against a putative myristoylated membrane protein encoded by
      grouper iridovirus 59L gene.
AB  - Groupers (Epinephelus spp.) are economically important fish species worldwide,
      and ranaviruses are major viral pathogens causing heavy economic losses in
      grouper aquaculture. In this study, the 59L gene of grouper iridovirus (GIV-59L)
      was cloned and characterized. This gene is 1521 bp and encodes a protein of 506
      amino acids with a predicted molecular mass of 53.9 kDa. Interestingly, GIV-59L
      and its homologs are found in all genera of the family Iridoviridae. A mouse
      monoclonal antibody specific for the C-terminal domain (amino acid positions 254
      506) of the GIV-59L protein, GIV-59L(760-1518)-MAb-21, was produced and proved to
      be well suited for use in a number of GIV immunoassays. RT-PCR, Western blotting,
      and cycloheximide and cytosine arabinoside drug inhibition analyses indicated
      that GIV-59L is a viral late gene in GIV-infected grouper kidney cells.
      Immunofluorescence analysis revealed that GIV-59L protein mainly accumulates in
      the cytoplasm of infected cells and is finally packed into a whole virus
      particle. The GIV-59L(760-1518)-MAb-21 characterized in this study could have
      widespread application in GIV immunodiagnostics and other research on GIV. In
      addition, the results presented here offer important insights into the
      pathogenesis of GIV. 

PMID- 25850400
TI  - Histopathological effects of atrazine on gills of Caspian kutum Rutilus frisii
      kutum fingerlings.
AB  - The use of chemical pesticides has increased environmental pollution and affects
      fishes as non-target organisms. To investigate the toxic effects of the widely
      used herbicide atrazine on Caspian kutum Rutilus frisii kutum fingerlings, fish
      were exposed to a sublethal concentration of half LC50 for 96 h. The main
      alterations visible in the gill tissue were detachment of the epithelium of the
      lamellae, necrosis, lamellar fusion, hyperplasia, club shaped lamellae, collapse
      of the lamellae, shrinkage and curling of the lamellae, and ultrastructural
      alterations such as necrosis of the apical microridges of the pavement cells.
      Results also showed that the gill ionocytes were fewer in number and larger in
      size in the atrazine-exposed fish. Atrazine appears to be highly toxic to Caspian
      kutum fingerlings even at a sublethal concentration (12.47 mg l(-1)) and acute
      exposure. This toxicity could affect gill respiration and ion regulation function
      of fingerlings by damaging tissue, pavement cells, and ionocytes.

PMID- 25850401
TI  - Temperature correlates with annual changes in Hematodinium perezi prevalence in
      blue crab Callinectes sapidus in Florida, USA.
AB  - Blue crabs Callinectes sapidus were monitored biannually throughout Florida, USA,
      for 2 yr using a highly sensitive, quantitative polymerase chain reaction (qPCR)
      to determine the spatial and temporal changes in prevalence and intensity of
      Hematodinium perezi infections during drought years. Despite persistent drought
      conditions, H. perezi infections were not universally found. Overall prevalence
      was 25.3% (95% CI: 22.8-28.1%) in 1066 crabs sampled from 6 locations
      (Jacksonville, Ormond Beach, Everglades City, Tampa Bay, Steinhatchee, and Panama
      City) from 2011 to 2012. Presence of H. perezi was consistently highest in winter
      season samples, ranging from 4.2-51.1% (3 locations) in 2011, to 32-83% (5
      locations) in 2012. The highest prevalence and intensities were observed in the
      winter samples from Everglades City. Previous studies have found that the
      prevalence of H. perezi in C. sapidus in temperate regions of the US East Coast
      shows seasonal peaks in early winter in Maryland and South Carolina and in fall
      and spring in Georgia. The seasonality of infections in the subtropical waters of
      Florida reinforces the concept that temperature is a strong factor that may
      override other drivers, such as drought. Seasonal H. perezi infections in Florida
      appear to be triggered by the parasite responding to an optimal temperature
      during the annual rise from the low temperature of winter when salinity is
      elevated. However, salinity alone is not sufficient to trigger an increase in
      prevalence of H. perezi in Florida. 

PMID- 25850402
TI  - Cell proteome variability of protistan mollusc parasite Perkinsus olseni among
      regions of the Spanish coast.
AB  - We evaluated the proteome variability of in vitro-cultured Perkinsus olseni cells
      deriving from 4 regions of the Spanish coast: the rias of Arousa and Pontevedra
      (Galicia, NW Spain), Carreras River in Huelva (Andalusia, SW Spain) and Delta de
      l'Ebre (Catalonia, NE Spain). P. olseni in vitro clonal cultures were produced
      starting from parasite isolates from 4 individual clams from each region. Those
      clonal cultures were used to extract cell proteins, which were separated by 2
      dimensional (2D) electrophoresis. Qualitative comparison of P. olseni protein
      expression profiles among regions was performed with PD Quest software. Around
      700 protein spots from parasites derived from each region were considered, from
      which 141 spots were shared by all the regions. Various spots were found to be
      exclusive to each region. Higher similarity was found among the proteomes of P.
      olseni from the Atlantic regions than between those from the Mediterranean and
      the Atlantic. A total of 54 spots were excised from the gels and sequenced.
      Nineteen proteins were annotated after searching in databases, 13 being shared by
      all the regions and 6 exclusive to 1 region. Most of the identified proteins were
      involved in glycolysis, oxidation/reduction, metabolism and response to stress.
      No direct evidence of P. olseni variability associated with virulence was found
      within the protein set analysed, although the differences in metabolic adaptation
      and stress response could be connected to pathogenicity. 

PMID- 25850403
TI  - Phaeohyphomycosis resulting in obstructive tracheitis in three green sea turtles
      Chelonia mydas stranded along the Florida coast.
AB  - Three wild immature green sea turtles Chelonia mydas were found alive but
      lethargic on the shores of the Indian River Lagoon and Gulf of Mexico in Florida,
      USA, and subsequently died. Necropsy findings in all 3 turtles included partial
      occlusion of the trachea by a mass comprised of granulomatous inflammation.
      Pigmented fungal hyphae were observed within the lesion by histology and were
      characterized by culture and sequencing of the internal transcribed spacer 2
      domain of the rRNA gene and D1/D2 region of the fungal 28s gene. The dematiaceous
      fungus species Veronaea botryosa was isolated from the tracheal mass in 2 cases,
      and genetic sequence of V. botryosa was detected by polymerase chain reaction in
      all 3 cases. Genetic sequencing and fungal cultures also detected other
      dematiaceous fungi, including a Cladosporium sp., an Ochroconis sp., and a
      Cochliobolus sp. These cases are the first report of phaeohyphomycosis caused by
      V. botryosa in wild marine animals. 

PMID- 25850404
TI  - Petromyzon marinus (Petromyzontidae), an unusual host for helminth parasites in
      western Europe.
AB  - The sea lamprey Petromyzon marinus, which is among the most phylogenetically
      ancient vertebrates, is a hematophagous ectoparasite that feeds on vertebrates
      and is considered vulnerable in Europe but is a pest in the North American Great
      Lakes. We conducted a literature review of helminth parasites of P. marinus and
      investigated postmetamorphic lampreys sampled in rivers and northeast Atlantic
      coastal waters (western France) during spawning migration. Based on the
      literature review, 16 helminth taxa have been recorded in P. marinus, among them
      14 in North America but only 2 in Europe, with no species in common between these
      areas. Specific parasites are lacking, and helminth parasites recorded in P.
      marinus are mostly opportunistic and are trophically transmitted to fish hosts
      with both extremely low prevalence and mean intensity. Thus, P. marinus seems an
      unusual host that is probably infected through accidental ingestion of parasites
      by microphagous larvae (ammocoetes) and/or hematophagous postmetamorphs. Our
      field study supports this hypothesis, since only a single third-stage larva of
      Anisakis simplex sensu stricto was found in 2 postmetamorphic P. marinus among
      the 115 individuals dissected. This opportunistic, trophically transmitted, and
      cosmopolitan nematode species has never been recorded in North American sea
      lampreys and only once in Galician rivers (southern Europe). Infestation pathways
      of P. marinus by A. simplex are proposed vis-a-vis the feeding strategy of
      postmetamorphs and fish host species which potentially harbor anisakid larvae in
      their musculature. More generally, the complexity of biotic interactions is
      discussed considering P. marinus both as a host for helminth parasites and as a
      parasite for hosts such as fish and mammals, which are also potential predators
      of sea lamprey. 

PMID- 25850405
TI  - Altered visual feedback modulates cortical excitability in a mirror-box-like
      paradigm.
AB  - Watching self-generated unilateral hand movements reflected in a mirror-oriented
      along the midsagittal plane-enhances the excitability of the primary motor cortex
      (M1) ipsilateral to the moving hand of the observer. Mechanisms detecting sensory
      motor conflicts generated by the mirror reflection of such movements might
      mediate this effect; if so, cortical excitability should be modulated by the
      magnitude of sensory-motor conflict. To this end, we explored the modulatory
      effects of an altered visual feedback on M1 excitability in a mirror-box-like
      paradigm, by increasing or decreasing the speed of the observed movement. Healthy
      subjects performed movements with their left index finger while watching a video
      of a hand superimposed to their right static hand, which was hidden from view.
      The hand observed in the video executed the same movement as the observer's left
      hand, but at slower, same, or faster paces. Motor evoked potentials (MEPs)
      induced by transcranial magnetic stimulation were measured from the first dorsal
      interosseous and the abductor digiti minimi of the participant's hidden resting
      hand. The excitability of the M1 ipsilateral to the moving hand was
      systematically modulated by the speed of the observed hand movement: the slower
      the observed movement, the greater the MEP amplitude from both muscles. This
      evidence shows that the magnitude of the visual-motor conflicts can be used to
      adjust the activity of the observer's motor system. Hence, an appropriate
      alteration of the visual feedback, here the reduction in the movement speed, may
      be useful to increase its modulatory effect on motor cortical excitability.

PMID- 25850406
TI  - Unified nature of bimanual movements revealed by separating the preparation of
      each arm.
AB  - Movement preparation of bimanual asymmetric movements is longer than bimanual
      symmetric movements in choice reaction time conditions, even when movements are
      cued directly by illuminating the targets (Blinch et al. in Exp Brain Res
      232(3):947-955, 2014). This bimanual asymmetric cost may be caused by increased
      processing demands on response programming, but this requires further
      investigation. The present experiment tested the demands on response programming
      for bimanual movements by temporally separating the preparation of each arm. This
      was achieved by precuing the target of one arm before the imperative stimulus. We
      asked: What was prepared in advance when one arm was precued? The answer to this
      question would suggest which process causes the bimanual asymmetric cost. Advance
      movement preparation was examined by comparing reaction times with and without a
      precue for the left target and by occasionally replacing the imperative stimulus
      with a loud, startling tone (120 dB). A startle tone releases whatever movement
      is prepared in advance with a much shorter reaction time than control trials
      (Carlsen et al. in Clin Neurophysiol 123(1):21-33, 2012). Participants made
      bimanual symmetric and asymmetric reaching movements in simple and 2-choice
      reaction time conditions and a condition with a precue for the left target. We
      found a bimanual asymmetric cost in 2-choice conditions, and the asymmetric cost
      was significantly smaller when the left target was precued. These results, and
      the results from startle trials, suggest (1) that the precued movement was not
      fully programmed but partially programmed before the imperative stimulus and (2)
      that the asymmetric cost was caused by increased processing demands on response
      programming. Overall, the results support the notion that bimanual movements are
      not the sum of two unimanual movements; instead, the two arms of a bimanual
      movement are unified into a functional unit. When one target is precued, this
      critical unification likely occurs during response programming.

PMID- 25850407
TI  - Arm dominance affects feedforward strategy more than feedback sensitivity during
      a postural task.
AB  - Handedness is a feature of human motor control that is still not fully
      understood. Recent work has demonstrated that the dominant and nondominant arm
      each excel at different behaviors and has proposed that this behavioral asymmetry
      arises from lateralization in the cerebral cortex: the dominant side specializes
      in predictive trajectory control, while the nondominant side is specialized for
      impedance control. Long-latency stretch reflexes are an automatic mechanism for
      regulating posture and have been shown to contribute to limb impedance. To
      determine whether long-latency reflexes also contribute to asymmetric motor
      behavior in the upper limbs, we investigated the effect of arm dominance on
      stretch reflexes during a postural task that required varying degrees of
      impedance control. Our results demonstrated slightly but significantly larger
      reflex responses in the biarticular muscles of the nondominant arm, as would be
      consistent with increased impedance control. These differences were attributed
      solely to higher levels of voluntary background activity in the nondominant
      biarticular muscles, indicating that feedforward strategies for postural
      stability may differ between arms. Reflex sensitivity, which was defined as the
      magnitude of the reflex response for matched levels of background activity, was
      not significantly different between arms for a broad subject population ranging
      from 23 to 51 years of age. These results indicate that inter-arm differences in
      feedforward strategies are more influential during posture than differences in
      feedback sensitivity, in a broad subject population. Interestingly, restricting
      our analysis to subjects under 40 years of age revealed a small increase in long
      latency reflex sensitivity in the nondominant arm relative to the dominant arm.
      Though our subject numbers were small for this secondary analysis, it suggests
      that further studies may be required to assess the influence of reflex
      lateralization throughout development.

PMID- 25850408
TI  - Resveratrol inhibits inflammation and ameliorates insulin resistant endothelial
      dysfunction via regulation of AMP-activated protein kinase and sirtuin 1
      activities.
AB  - BACKGROUND: Resveratrol is a phytoalexin with beneficial effects on human health.
      The aim of the present study was to investigate the effects of resveratrol on
      endothelial dysfunction involved in insulin signaling and inflammation. METHODS:
      Endothelial cells were stimulated with palmitate (PA) to induce insulin
      resistance characterized by a loss of insulin-mediated nitric oxide (NO)
      production. Diabetes was induced in rats by fructose feeding. The effects of
      resveratrol and the mechanisms involved were investigated using an aortic
      relaxation assay and Western blot analysis. RESULTS: In endothelial cells, 0.1-10
      MUmol/L resveratrol suppressed IkappaB kinase beta (IKKbeta)/nuclear factor
      kappaB phosphorylation, as well as tumor necrosis factor-alpha and interleukin-6
      production, and restored the insulin receptor substrate-1 (Irs-1)/Akt/endothelial
      NO synthase signaling pathway. Furthermore, resveratrol effectively inhibited the
      mitogenic actions of insulin by decreasing the secretion of endothelin-1 and
      plasminogen activator inhibitor-1. It also positively regulated AMP-activated
      kinase (AMPK) and sirtuin 1 (SIRT1) activation, which contributed to the
      inhibition of inflammation implicated in endothelial insulin resistance.
      Stimulation with PA and long term-fructose feeding impaired insulin-mediated
      vessel dilation in rat aorta, whereas pretreatment of aortic rings with
      resveratrol (0.1-10 MUmol/L) or treatment of rats with 5 or 20 mg/kg resveratrol
      counteracted these changes. CONCLUSION: The results indicate that resveratrol
      inhibits inflammation and facilitates insulin phosphatidylinositol 3-kinase
      signaling by beneficial modulation of IRS-1 function partly via regulation of
      AMPK and SIRT1 activity in the endothelium.

PMID- 25850409
TI  - Identification of receptor-type protein tyrosine phosphatase MU as a new marker
      for osteocytes.
AB  - Osteocytes are the predominant cells in bone, where they form a cellular network
      and display important functions in bone homeostasis, phosphate metabolism and
      mechanical transduction. Several proteins strongly expressed by osteocytes are
      involved in these processes, e.g., sclerostin, DMP-1, PHEX, FGF23 and MEPE, while
      others are upregulated during differentiation of osteoblasts into osteocytes,
      e.g., osteocalcin and E11. The receptor-type protein tyrosine phosphatase u
      (RPTPMU) has been described to be expressed in cells which display a cellular
      network, e.g., endothelial and neuronal cells, and is implied in
      mechanotransduction. In a capillary outgrowth assay using metatarsals derived
      from RPTPMU-knock-out/LacZ knock-in mice, we observed that the capillary
      structures grown out of the metatarsals were stained blue, as expected.
      Surprisingly, cells within the metatarsal bone tissue were positive for LacZ
      activity as well, indicating that RPTPMU is also expressed by osteocytes.
      Subsequent histochemical analysis showed that within bone, RPTPMU is expressed
      exclusively in early-stage osteocytes. Analysis of bone marrow cell cultures
      revealed that osteocytes are present in the nodules and an enzymatic assay
      enabled the quantification of the amount of osteocytes. No apparent bone
      phenotype was observed when tibiae of RPTPMU-knock-out/LacZ knock-in mice were
      analyzed by MUCT at several time points during aging, although a significant
      reduction in cortical bone was observed in RPTPMU-knock-out/LacZ knock-in mice at
      20 weeks. Changes in trabecular bone were more subtle. Our data show that RPTPMU
      is a new marker for osteocytes.

PMID- 25850410
TI  - Human sperm molecular anatomy: the enzyme 5alpha-reductase (SRD5A) is present in
      the sperm and may be involved in the varicocele-related infertility.
AB  - The most common cause of male infertility is the testicular varicocele, a
      condition that impairs production and decreases quality of sperm. Male fertility
      also strictly depends on androgens acting through their own receptor. The enzyme
      5alpha-reductase (SRD5A) is involved in the conversion of testosterone to 5alpha
      dihydrotestosterone, both required for the development and maintenance of male
      reproductive function. Here, we evaluated, by western blotting analysis, the
      presence of SRD5A in human ejaculated spermatozoa and evidenced differences in
      sperm SRD5A content between healthy donors and varicocele-affected patients.
      Additionally, SRD5A sperm ultrastructural localization was also assessed by
      transmission electron microscopy and immunogold assay. We evidenced that SRD5A
      enzyme is present in the human spermatozoa and that its cellular content is
      lowered in sperm samples from varicocele patients compared to healthy subjects.
      The presence of SRD5A in human ejaculated spermatozoa highlights the potential
      role of this enzyme in sperm physiopathology suggesting that the decrease in its
      content, by affecting the conversion of testosterone into 5alpha
      dihydrotestosterone, may be an important additional mechanism involved in the
      harmful effect of varicocele in male fertility. 

PMID- 25850411
TI  - Allan-Herndon-Dudley syndrome with unusual profound sensorineural hearing loss.
AB  - The Allan-Herndon-Dudley syndrome is caused by mutations in the thyroid hormone
      transporter, Monocarboxylate transporter 8 (MCT8). It is characterized by
      profound intellectual disability and abnormal thyroid function. We report on a
      patient with Allan-Herndon-Dudley syndrome (AHDS) with profound sensorineural
      hearing loss which is not usually a feature of AHDS and which may have been due
      to a coexisting nonsense mutation in Microphthalmia-associated transcription
      factor (MITF).

PMID- 25850412
TI  - Erratum: A vlincRNA participates in senescence maintenance by relieving H2AZ
      mediated repression at the INK4 locus.

PMID- 25850414
TI  - The eating disorder examination: reliability and validity of the Italian version.
AB  - OBJECTIVE: To examine the psychometric characteristics of the Italian language
      version of the latest edition of the eating disorder examination (EDE). METHODS:
      An Italian version of the EDE (17th edition) was designed and administered to 185
      in- and outpatients with eating disorders and 60 age-matched controls. Its
      internal consistency, inter-rater reliability, short-term (7-23 days) test-retest
      reliability and criterion validity were evaluated. RESULTS: Internal consistency
      was high for all four original EDE subscales. Inter-rater reliability was
      excellent for global EDE scores and original subscales (>=0.93), and for eating
      disorder behaviours (>=0.89). Test-retest reliability was good for global EDE
      scores and original subscales (0.57-0.80), objective bulimic episodes and days,
      vomiting episodes, laxative and diuretic misuse episodes, and excessive
      exercising (>=0.82), but unsatisfactory for subjective bulimic episodes and days.
      Patients with eating disorders displayed significantly higher EDE scores than age
      matched controls, demonstrating the good criterion validity of the instrument.
      CONCLUSIONS: The Italian version of the EDE 17.0D has adequate psychometric
      properties and can therefore be recommended for examining Italian patients with
      eating disorders in clinical and research settings.

PMID- 25850413
TI  - Enhanced recovery protocols (ERP) in robotic cystectomy surgery. Review of
      current status and trends.
AB  - Open radical cystectomy with pelvic lymphadenectomy and urinary diversion is
      associated with a high complication rate. Robotic-assisted laparoscopic radical
      cystectomy is increasingly performed in many urologic surgical departments in an
      effort to reduce surgical stress and decrease perioperative morbidity. Robotic
      cystectomy survival studies demonstrate similar oncologic outcomes compared to
      the open procedure. Enhanced recovery protocols (ERP) after major surgery are
      multimodal perioperative interventions to reduce surgical stress, complications,
      and patient convalescence. Evidence for different ERP interventions are currently
      mainly from colorectal surgery and recently adapted to major urologic operations
      including cystectomy. Guidelines for perioperative care after open radical
      cystectomy for bladder cancer were recently published, but these recommendations
      may differ when considering a robotic approach. Therefore, we look at the current
      evidence for ERP in both open and robotic radical cystectomy and the potential
      for improving ERPs in robotic cystectomy by utilizing a totally intracorporeal
      robotic cystectomy approach. We also present the Karolinska ERP currently
      utilized in totally intracorporeal robotic cystectomy. 

PMID- 25850415
TI  - Evaluation of the sensitivity of bacterial and yeast cells to cold atmospheric
      plasma jet treatments.
AB  - The focus of this research was first to determine the influence of the
      atmospheric plasma drive frequency on the generation of atomic oxygen species and
      its correlation with the reduction of bacterial load after treatment in vitro.
      The treatments were carried out using a helium-plasma jet source called
      PlasmaStreamTM. The susceptibility of multiple microbial cell lines was
      investigated in order to compare the response of gram-positive and gram-negative
      bacteria, as well as a yeast cell line to the atmospheric plasma treatment. It
      was observed for the source evaluated that at a frequency of 160 kHz, increased
      levels of oxygen-laden active species (i.e., OH, NO) were generated. At this
      frequency, the maximum level of bacterial inactivation in vitro was also
      achieved. Ex vivo studies (using freshly excised porcine skin as a human analog)
      were also carried out to verify the antibacterial effect of the plasma jet
      treatment at this optimal operational frequency and to investigate the effect of
      treatment duration on the reduction of bacterial load. The plasma jet treatment
      was found to yield a 4 log reduction in bacterial load after 6 min of treatment,
      with no observable adverse effects on the treatment surface. The gram-negative
      bacterial cell lines were found to be far more susceptible to the atmospheric
      plasma treatments than the gram-positive bacteria. Flow cytometric analysis of
      plasma treated bacterial cells (Escherichia coli) was conducted in order to
      attain a fundamental understanding of the mode of action of the treatment on
      bacteria at a cellular level. This study showed that after treatment with the
      plasma jet, E. coli cells progressed through the following steps of cell death;
      the inactivation of transport systems, followed by depolarization of the
      cytoplasmic membrane, and finally permeabilization of the cell wall. 

PMID- 25850416
TI  - Numerical simulation of an atmospheric pressure RF-driven plasma needle and heat
      transfer to adjacent human skin using COMSOL.
AB  - Plasma medicine is an emerging field where plasma physics is used for
      therapeutical applications. Temperature is an important factor to take into
      account with respect to the applications of plasma to biological systems. During
      the treatment, the tissue temperature could increase to critical values. In this
      work, a model is presented, which is capable of predicting the skin temperature
      during a treatment with a radio frequency driven plasma needle. The main gas was
      helium. To achieve this, a discharge model was coupled to a heat transfer and
      fluid flow model. The results provide maximum application times for different
      power depositions in order to avoid reaching critical skin temperatures. 

PMID- 25850417
TI  - Ocular oncology in India.

PMID- 25850418
TI  - What doctors have in common with architects--part 1: a manual art.

PMID- 25850419
TI  - Toxicological and Genotoxicity Assessment of a Dihydroquercetin-Rich Dahurian
      Larch Tree (Larix gmelinii Rupr) Extract (Lavitol).
AB  - Safety assessment is reported of an orally ingested dihydroquercetin-rich extract
      (Lavitol) derived from the Dahurian larch tree, used as a food additive and as a
      dietary supplement ingredient. Dihydroquercetin, a potent antioxidant, is also
      known as taxifolin. The results of genotoxicity and toxicological tests (Comet
      assay, micronucleus test in human lymphocytes, chromosomal aberration test,
      subacute 7-day oral toxicity study, subchronic 90-day toxicology study with
      histopathologies, and, prenatal and postnatal developmental toxicity studies) on
      the extract provide further support for the safety of its consumption as a food
      supplement and food additive. 

PMID- 25850420
TI  - Controlled in vivo swimming of a swarm of bacteria-like microrobotic flagella.
AB  - In vivo imaging and actuation of a swarm of magnetic helical microswimmers by
      external magnetic fields (less than 10 mT) in deep tissue is demonstrated for the
      first time. This constitutes a major milestone in the field, yielding a
      generation of micrometer-scale transporters with numerous applications in
      biomedicine including synthetic biology, assisted fertilization, and drug/gene
      delivery. 

PMID- 25850421
TI  - Engineering protein folding and translocation improves heterologous protein
      secretion in Saccharomyces cerevisiae.
AB  - Saccharomyces cerevisiae is widely used as a producer of heterologous proteins of
      medical and industrial interest. Numerous efforts have been made to overcome
      bottlenecks in protein expression and secretion. However, the effect of
      engineering protein translocation to heterologous protein secretion has not been
      studied extensively in S. cerevisiae. In this work, we confirmed that
      heterologous protein expression in S. cerevisiae induced the unfolded protein
      response (UPR). To enhance protein folding capacity, the endoplasmic reticulum
      (ER) chaperone protein BiP and the disulfide isomerase Pdi1p were each over
      expressed, and the secretion of three heterologous proteins, beta-glucosidase,
      endoglucanase, and alpha-amylase, was improved. The impact of engineering key
      translocation components was also studied. The over-expression of co
      translational translocation components Srp14p and Srp54p enhanced the secretion
      of three heterologous proteins (beta-glucosidase, endoglucanase, and alpha
      amylase), but over-expressing the cytosolic chaperone Ssa1p (involved in post
      translational translocation) only enhanced the secretion of beta-glucosidase. By
      engineering both co-translational translocation and protein folding, we obtained
      strains with beta-glucosidase, endoglucanase, and alpha-amylase activities
      increased by 72%, 60%, and 103% compared to the controls. Our results show that
      protein translocation may be a limiting factor for heterologous protein
      production.

PMID- 25850422
TI  - Two novel sodium channel mutations associated with resistance to indoxacarb and
      metaflumizone in the diamondback moth, Plutella xylostella.
AB  - Indoxacarb and metaflumizone belong to a relatively new class of sodium channel
      blocker insecticides (SCBIs). Due to intensive use of indoxacarb, field-evolved
      indoxacarb resistance has been reported in several lepidopteran pests, including
      the diamondback moth Plutella xylostella, a serious pest of cruciferous crops. In
      particular, the BY12 population of P. xylostella, collected from Baiyun,
      Guangdong Province of China in 2012, was 750-fold more resistant to indoxacarb
      and 70-fold more resistant to metaflumizone compared with the susceptible Roth
      strain. Comparison of complementary DNA sequences encoding the sodium channel
      genes of Roth and BY12 revealed two point mutations (F1845Y and V1848I) in the
      sixth segment of domain IV of the PxNav protein in the BY population. Both
      mutations are located within a highly conserved sequence region that is predicted
      to be involved in the binding sites of local anesthetics and SCBIs based on
      mammalian sodium channels. A significant correlation was observed among 10 field
      collected populations between the mutant allele (Y1845 or I1848) frequencies
      (1.7% to 52.5%) and resistance levels to both indoxacarb (34- to 870-fold) and
      metaflumizone (1- to 70-fold). The two mutations were never found to co-exist in
      the same allele of PxNav , suggesting that they arose independently. This is the
      first time that sodium channel mutations have been associated with high levels of
      resistance to SCBIs. F1845Y and V1848I are molecular markers for resistance
      monitoring in the diamondback moth and possibly other insect pest species. 

PMID- 25850423
TI  - Isolation and full-genome sequence of two reticuloendotheliosis virus strains
      from mixed infections with Marek's disease virus in China.
AB  - Reticuloendotheliosis virus (REV), classified as a gammaretrovirus, has a variety
      of hosts, including chickens, ducks, geese, turkeys, and wild birds. REV causes a
      series of pathological syndromes, especially the immunosuppression of the host,
      which may lead to an increased susceptibility to other pathogens, thus greatly
      damaging the poultry industry. Mixed infections of REV and Marek's disease virus
      (MDV) have been reported in many countries, including China. Previous reports
      revealed that MDV vaccines were not efficacious, and even less-virulent MDV
      strains would cause some losses due to mixed infections with REV. Additionally,
      contaminants in the MDV vaccine might be the main source of REV. In this study,
      two clinical samples were collected from two flocks of chickens that were
      diagnosed with MDV. Subsequently, two REV isolates were obtained from the
      clinical samples. The isolates, named CY1111 and SY1209, were further confirmed
      through an indirect immunofluorescence assay and electron microscopy. Complete
      genome sequences of the two REV strains were determined to test the relationship
      between them and other REV strains. Phylogenetic trees showed that the two REV
      strains were closely related to most REV strains that were isolated from a
      variety of hosts. Therefore, REVs might spread freely among these hosts under
      natural conditions. Additionally, most REV strains in China were in the same
      clade. The present work offers some information regarding REV in China. 

PMID- 25850424
TI  - Spatial analysis of gastroschisis in the National Birth Defects Prevention Study.
AB  - BACKGROUND: Gastroschisis is a birth defect where loops of bowel are protruding
      from the abdominal wall at birth. Previous research has suggested that
      gastroschisis cases can occur in clusters. The objective of this study was to
      identify if there were areas of elevated gastroschisis risk using data from the
      National Birth Defects Prevention Study (NBDPS), 1997 through 2007. METHODS: We
      obtained data on cases (n = 371) through population-based birth defects
      surveillance systems in Arkansas, California, and Utah; controls (n = 2359) were
      selected from the same geographic areas as cases. Mothers were interviewed on
      demographic information and exposures during pregnancy, including residential
      history. We used first trimester maternal addresses and generalized additive
      models to create a continuous map surface of odds ratios (OR) by smoothing over
      latitude and longitude. Permutation tests were used to assess whether location of
      maternal residence was important and identify locations with statistically
      significant ORs. RESULTS: In Arkansas, adjusted ORs in the southwest corner were
      2.0 and the global deviance was not statistically significant (p-value: 0.57).
      Adjusted ORs for California indicated areas of increased risk with ORs 1.3 (p
      value: 0.34). In Utah, the adjusted ORs were elevated (OR: 2.4) in the south
      eastern corner of the study area (p-value: 0.34). CONCLUSION: The results of this
      study, while not statistically significant, suggest there were spatial variations
      in gastroschisis births. We cannot rule out that these variations were due to
      edge effects or residual confounding.

PMID- 25850426
TI  - X Chromosome and Autosome Dosage Responses in Drosophila melanogaster Heads.
AB  - X chromosome dosage compensation is required for male viability in Drosophila.
      Dosage compensation relative to autosomes is two-fold, but this is likely to be
      due to a combination of homeostatic gene-by-gene regulation and chromosome-wide
      regulation. We have baseline values for gene-by-gene dosage compensation on
      autosomes, but not for the X chromosome. Given the evolutionary history of sex
      chromosomes, these baseline values could differ. We used a series of deficiencies
      on the X and autosomes, along with mutations in the sex-determination gene
      transformer-2, to carefully measure the sex-independent X-chromosome response to
      gene dosage in adult heads by RNA sequencing. We observed modest and
      indistinguishable dosage compensation for both X chromosome and autosome genes,
      suggesting that the X chromosome is neither inherently more robust nor sensitive
      to dosage change. 

PMID- 25850428
TI  - Mood instability as a precursor to depressive illness: A prospective and
      mediational analysis.
AB  - OBJECTIVE: Mood instability levels are high in depression, but temporal
      precedence and potential mechanisms are unknown. Hypotheses tested were as
      follows: (1) mood instability is associated with depression cross-sectionally,
      (2) mood instability predicts new onset and maintenance of depression
      prospectively and (3) the mood instability and depression link are mediated by
      sleep problems, alcohol abuse and life events. METHOD: Data from the National
      Psychiatric Morbidity Survey 2000 at baseline (N = 8580) and 18-month follow-up
      (N = 2413) were used. Regression modeling controlling for socio-demographic
      factors, anxiety and hypomanic mood was conducted. Multiple mediational analyses
      were used to test our conceptual path model. RESULTS: Mood instability was
      associated with depression cross-sectionally (odds ratio: 5.28; 95% confidence
      interval: [3.67, 7.59]; p < 0.001) and predicted depression inception (odds
      ratio: 2.43; 95% confidence interval: [1.03-5.76]; p = 0.042) after controlling
      for important confounders. Mood instability did not predict maintenance of
      depression. Sleep difficulties and severe problems with close friends and family
      significantly mediated the link between mood instability and new onset depression
      (23.05% and 6.19% of the link, respectively). Alcohol abuse and divorce were not
      important mediators in the model. CONCLUSION: Mood instability is a precursor of
      a depressive episode, predicting its onset. Difficulties in sleep are a
      significant part of the pathway. Interventions targeting mood instability and
      sleep problems have the potential to reduce the risk of depression.

PMID- 25850427
TI  - Insights into Ongoing Evolution of the Hexachlorocyclohexane Catabolic Pathway
      from Comparative Genomics of Ten Sphingomonadaceae Strains.
AB  - Hexachlorocyclohexane (HCH), a synthetic organochloride, was first used as a
      broad-acre insecticide in the 1940s, and many HCH-degrading bacterial strains
      have been isolated from around the globe during the last 20 years. To date, the
      same degradation pathway (the lin pathway) has been implicated in all strains
      characterized, although the pathway has only been characterized intensively in
      two strains and for only a single HCH isomer. To further elucidate the evolution
      of the lin pathway, we have biochemically and genetically characterized three HCH
      degrading strains from the Czech Republic and compared the genomes of these and
      seven other HCH-degrading bacterial strains. The three new strains each yielded a
      distinct set of metabolites during their degradation of HCH isomers. Variable
      assembly of the pathway is a common feature across the 10 genomes, eight of which
      (including all three Czech strains) were either missing key lin genes or
      containing duplicate copies of upstream lin genes (linA-F). The analysis also
      confirmed the important role of horizontal transfer mediated by insertion
      sequence IS6100 in the acquisition of the pathway, with a stronger association of
      IS6100 to the lin genes in the new strains. In one strain, a linA variant was
      identified that likely caused a novel degradation phenotype involving a shift in
      isomer preference. This study identifies a number of strains that are in the
      early stages of lin pathway acquisition and shows that the state of the pathway
      can explain the degradation patterns observed. 

PMID- 25850429
TI  - Bevacizumab in recurrent glioblastoma: five informative patient scenarios.
AB  - Glioblastoma is the most common and malignant primary brain tumour in adults.
      Maximum feasible surgical resection, radiotherapy and temozolomide chemotherapy
      at initial diagnosis have improved prognosis but rapid recurrence is typical and
      survival remains brief. There is an urgent need for effective new treatments and
      approval of the antiangiogenic agent bevacizumab for recurrent glioblastoma by
      Health Canada in 2009 has been the most notable recent therapeutic advance for
      this disease. This review with illustrative case studies highlights how
      bevacizumab has been incorporated into the treatment of glioblastoma in Canada
      and describes the ongoing controversies surrounding its clinical application. 

PMID- 25850430
TI  - Assessing impairment of executive function and psychomotor speed in premanifest
      and manifest Huntington's disease gene-expansion carriers.
AB  - Executive functions (EF) and psychomotor speed (PMS) has been widely studied in
      Huntington's disease (HD). Most studies have focused on finding markers of
      disease progression by comparing group means at different disease stages. Our aim
      was to investigate performances on nine measures of EF and PMS in a group of
      premanifest and manifest HD-gene expansion carriers and to investigate which
      measures were most sensitive for assessment of individual patients by analyzing
      frequencies of impaired performances relative to healthy controls. We recruited
      HD gene-expansion carriers, 48 manifest and 50 premanifest and as controls 39
      healthy gene-expansion negative individuals. All participants underwent
      neurological examination and neuropsychological testing with nine cognitive
      measures. The frequency of impairment was investigated using cutoff scores. In
      group comparisons the manifest HD gene-expansion carriers scored significantly
      worse than controls on all tests and in classification of individual scores the
      majority of scores were classified as probably impaired (10th percentile) or
      impaired (5th percentile) with Symbol Digit Modalities Test (SDMT) being the most
      frequently impaired. Group comparisons of premanifest HD gene-expansion carriers
      and healthy controls showed significant differences on SDMT and Alternating
      fluency tests. Nevertheless the frequencies of probably impaired and impaired
      scores on individual tests were markedly higher for Alternating and Lexical
      fluency tests than for SDMT. We found distinct group differences in frequency of
      impairment on measures of EF and PMS in manifest and premanifest HD gene
      expansion carriers. Our results indicate to what degree these measures can be
      expected to be clinically impaired.

PMID- 25850431
TI  - [Transcripts from automated external defibrillator are important].
AB  - We report a case where a 16-year-old girl with diabetes who suffered aborted
      cardiac arrest. Out of hospital the patient received a shock from an automated
      external defibrillator (AED) due to ventricular fibrillation (VF). Neither the VF
      nor the shock were reported to the receiving hospital. After referral to another
      hospital the AED transcript was read and the patient received an implantable
      cardioverter-defibrillator. Transcripts from AEDs used in the resuscitation of
      patients with cardiac arrest should always be analysed in order to optimize the
      diagnostic process and secure correct treatment. 

PMID- 25850432
TI  - The silkworm GSTe4 is sensitive to phoxim and protects HEK293 cells against UV
      induced cell apoptosis.
AB  - Glutathione S-transferases (GSTs, EC 2.5.1.18) are a family of super enzymes with
      multiple functions that play a major role in the detoxification of endogenous and
      xenobiotic compounds. In our previous study, we have predicted 23 putative
      cytosolic GSTs in the silkworm genome using bioinformatic methods. In this study,
      we cloned and studied the insect-specific epsilon-class GST gene GSTe4 from the
      silkworm, Bombyx mori. The recombinant BmGSTe4 (Bac-BmGSTe4) was overexpressed in
      SF-9 cell lines, and it was found to have effective GST activity. We also found
      that the expression of BmGSTe4 was especially down-regulated after the silkworms
      were fumigated with or ingested phoxim. Moreover, BmGSTe4 protected HEK293 cells
      against UV-induced cell apoptosis. These results demonstrated that BmGSTe4 has
      GST activity, is sensitive to phoxim, and plays a role in inhibition of UV
      induced cell apoptosis. 

PMID- 25850433
TI  - Integrated Stable Isotope Labeling by Amino Acids in Cell Culture (SILAC) and
      Isobaric Tags for Relative and Absolute Quantitation (iTRAQ) Quantitative
      Proteomic Analysis Identifies Galectin-1 as a Potential Biomarker for Predicting
      Sorafenib Resistance in Liver Cancer.
AB  - Sorafenib has become the standard therapy for patients with advanced
      hepatocellular carcinoma (HCC). Unfortunately, most patients eventually develop
      acquired resistance. Therefore, it is important to identify potential biomarkers
      that could predict the efficacy of sorafenib. To identify target proteins
      associated with the development of sorafenib resistance, we applied stable
      isotope labelling with amino acids in cell culture (SILAC)-based quantitative
      proteomic approach to analyze differences in protein expression levels between
      parental HuH-7 and sorafenib-acquired resistance HuH-7 (HuH-7(R)) cells in vitro,
      combined with an isobaric tags for relative and absolute quantitation (iTRAQ)
      quantitative analysis of HuH-7 and HuH-7(R) tumors in vivo. In total, 2,450
      quantified proteins were identified in common in SILAC and iTRAQ experiments,
      with 81 showing increased expression (>2.0-fold) with sorafenib resistance and 75
      showing decreased expression (<0.5-fold). In silico analyses of these
      differentially expressed proteins predicted that 10 proteins were related to
      cancer with involvements in cell adhesion, migration, and invasion. Knockdown of
      one of these candidate proteins, galectin-1, decreased cell proliferation and
      metastasis in HuH-7(R) cells and restored sensitivity to sorafenib. We verified
      galectin-1 as a predictive marker of sorafenib resistance and a downstream target
      of the AKT/mTOR/HIF-1alpha signaling pathway. In addition, increased galectin-1
      expression in HCC patients' serum was associated with poor tumor control and low
      response rate. We also found that a high serum galectin-1 level was an
      independent factor associated with poor progression-free survival and overall
      survival. In conclusion, these results suggest that galectin-1 is a possible
      biomarker for predicting the response of HCC patients to treatment with
      sorafenib. As such, it may assist in the stratification of HCC and help direct
      personalized therapy. 

PMID- 25850434
TI  - Online Peptide fractionation using a multiphasic microfluidic liquid
      chromatography chip improves reproducibility and detection limits for
      quantitation in discovery and targeted proteomics.
AB  - Comprehensive proteomic profiling of biological specimens usually requires
      multidimensional chromatographic peptide fractionation prior to mass
      spectrometry. However, this approach can suffer from poor reproducibility because
      of the lack of standardization and automation of the entire workflow, thus
      compromising performance of quantitative proteomic investigations. To address
      these variables we developed an online peptide fractionation system comprising a
      multiphasic liquid chromatography (LC) chip that integrates reversed phase and
      strong cation exchange chromatography upstream of the mass spectrometer (MS). We
      showed superiority of this system for standardizing discovery and targeted
      proteomic workflows using cancer cell lysates and nondepleted human plasma. Five
      step multiphase chip LC MS/MS acquisition showed clear advantages over analyses
      of unfractionated samples by identifying more peptides, consuming less sample and
      often improving the lower limits of quantitation, all in highly reproducible,
      automated, online configuration. We further showed that multiphase chip LC
      fractionation provided a facile means to detect many N- and C-terminal peptides
      (including acetylated N terminus) that are challenging to identify in complex
      tryptic peptide matrices because of less favorable ionization characteristics.
      Given as much as 95% of peptides were detected in only a single salt fraction
      from cell lysates we exploited this high reproducibility and coupled it with
      multiple reaction monitoring on a high-resolution MS instrument (MRM-HR). This
      approach increased target analyte peak area and improved lower limits of
      quantitation without negatively influencing variance or bias. Further, we showed
      a strategy to use multiphase LC chip fractionation LC-MS/MS for ion library
      generation to integrate with SWATH(TM) data-independent acquisition quantitative
      workflows. All MS data are available via ProteomeXchange with identifier
      PXD001464. 

PMID- 25850435
TI  - A Phosphoproteomic Comparison of B-RAFV600E and MKK1/2 Inhibitors in Melanoma
      Cells.
AB  - Inhibitors of oncogenic B-RAF(V600E) and MKK1/2 have yielded remarkable responses
      in B-RAF(V600E)-positive melanoma patients. However, the efficacy of these
      inhibitors is limited by the inevitable onset of resistance. Despite the fact
      that these inhibitors target the same pathway, combination treatment with B
      RAF(V600E) and MKK1/2 inhibitors has been shown to improve both response rates
      and progression-free survival in B-RAF(V600E) melanoma patients. To provide
      insight into the molecular nature of the combinatorial response, we used
      quantitative mass spectrometry to characterize the inhibitor-dependent
      phosphoproteome of human melanoma cells treated with the B-RAF(V600E) inhibitor
      PLX4032 (vemurafenib) or the MKK1/2 inhibitor AZD6244 (selumetinib). In three
      replicate experiments, we quantified changes at a total of 23,986 phosphosites on
      4784 proteins. This included 1317 phosphosites that reproducibly decreased in
      response to at least one inhibitor. Phosphosites that responded to both
      inhibitors grouped into networks that included the nuclear pore complex, growth
      factor signaling, and transcriptional regulators. Although the majority of
      phosphosites were responsive to both inhibitors, we identified 16 sites that
      decreased only in response to PLX4032, suggesting rare instances where oncogenic
      B-RAF signaling occurs in an MKK1/2-independent manner. Only two phosphosites
      were identified that appeared to be uniquely responsive to AZD6244. When cells
      were treated with the combination of AZD6244 and PLX4032 at subsaturating
      concentrations (30 nm), responses at nearly all phosphosites were additive. We
      conclude that AZD6244 does not substantially widen the range of phosphosites
      inhibited by PLX4032 and that the benefit of the drug combination is best
      explained by their additive effects on suppressing ERK1/2 signaling. Comparison
      of our results to another recent ERK1/2 phosphoproteomics study revealed a
      surprising degree of variability in the sensitivity of phosphosites to MKK1/2
      inhibitors in human cell lines, revealing unexpected cell specificity in the
      molecular responses to pathway activation. 

PMID- 25850436
TI  - Unveiling Contacts within Macromolecular Assemblies by Solving Minimum Weight
      Connectivity Inference (MWC) Problems.
AB  - Consider a set of oligomers listing the subunits involved in subcomplexes of a
      macromolecular assembly, obtained e.g. using native mass spectrometry or affinity
      purification. Given these oligomers, connectivity inference (CI) consists of
      finding the most plausible contacts between these subunits, and minimum
      connectivity inference (MCI) is the variant consisting of finding a set of
      contacts of smallest cardinality. MCI problems avoid speculating on the total
      number of contacts but yield a subset of all contacts and do not allow exploiting
      a priori information on the likelihood of individual contacts. In this context,
      we present two novel algorithms, MILP-W and MILP-WB. The former solves the
      minimum weight connectivity inference (MWCI), an optimization problem whose
      criterion mixes the number of contacts and their likelihood. The latter uses the
      former in a bootstrap fashion to improve the sensitivity and the specificity of
      solution sets.Experiments on three systems (yeast exosome, yeast proteasome lid,
      human eIF3), for which reference contacts are known (crystal structure, cryo
      electron microscopy, cross-linking), show that our algorithms predict contacts
      with high specificity and sensitivity, yielding a very significant improvement
      over previous work, typically a twofold increase in sensitivity.The software
      accompanying this paper is made available and should prove of ubiquitous interest
      whenever connectivity inference from oligomers is faced. 

PMID- 25850437
TI  - Bacteria-mediated effects of antibiotics on Daphnia nutrition.
AB  - In polluted environments, contaminant effects may be manifested via both direct
      toxicity to the host and changes in its microbiota, affecting bacteria-host
      interactions. In this context, particularly relevant is exposure to antibiotics
      released into environment. We examined effects of the antibiotic trimethoprim on
      microbiota of Daphnia magna and concomitant changes in the host feeding. In
      daphnids exposed to 0.25 mg L(-1) trimethoprim for 24 h, the microbiota was
      strongly affected, with (1) up to 21-fold decrease in 16S rRNA gene abundance and
      (2) a shift from balanced communities dominated by Curvibacter, Aquabacterium,
      and Limnohabitans in controls to significantly lower diversity under dominance of
      Pelomonas in the exposed animals. Moreover, decreased feeding and digestion was
      observed in the animals exposed to 0.25-2 mg L(-1) trimethoprim for 48 h and then
      fed 14C-labeled algae. Whereas the proportion of intact algal cells in the guts
      increased with increased trimethoprim concentration, ingestion and incorporation
      rates as well as digestion and incorporation efficiencies decreased
      significantly. Thus, antibiotics may impact nontarget species via changes in
      their microbiota leading to compromised nutrition and, ultimately, growth. These
      bacteria-mediated effects in nontarget organisms may not be unique for
      antibiotics, but also relevant for environmental pollutants of various nature.

PMID- 25850438
TI  - Evaluation of an alginate-gelatine crosslinked hydrogel for bioplotting.
AB  - Using additive manufacturing to create hydrogel scaffolds which incorporate
      homogeneously distributed, immobilized cells in the context of biofabrication
      approaches represents an emerging and expanding field in tissue engineering.
      Applying hydrogels for additive manufacturing must consider the material
      processing properties as well as their influence on the immobilized cells. In
      this work alginate-dialdehyde (ADA), a partially oxidized alginate, was used as a
      basic material to improve the physico-chemical properties of the hydrogel for
      cell immobilization. At first, the processing ability of the gel using a
      bioplotter and the compatibility of the process with MG-63 osteoblast like cells
      were investigated. The metabolic and mitochondrial activities increased at the
      beginning of the incubation period and they balanced at a relatively high level
      after 14-28 days of incubation. During this incubation period the release of
      vascular endothelial growth factor-A also increased. After 28 days of incubation
      the cell morphology showed a spreading morphology and cells were seen to move out
      of the scaffold struts covering the whole scaffold structure. The reproducible
      processing capability of alginate-gelatine (ADA-GEL) and the compatibility with
      MG-63 cells were proven, thus the ADA-GEL material is highlighted as a promising
      matrix for applications in biofabrication.

PMID- 25850425
TI  - Quality of anticoagulation control in preventing adverse events in patients with
      heart failure in sinus rhythm: Warfarin versus Aspirin in Reduced Cardiac
      Ejection Fraction trial substudy.
AB  - BACKGROUND: The aim of this study is to examine the relationship between time in
      the therapeutic range (TTR) and clinical outcomes in heart failure patients in
      sinus rhythm treated with warfarin. METHODS AND RESULTS: We used data from the
      Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial to
      assess the relationship of TTR with the WARCEF primary outcome (ischemic stroke,
      intracerebral hemorrhage, or death), with death alone, ischemic stroke alone,
      major hemorrhage alone, and net clinical benefit (primary outcome and major
      hemorrhage combined). Multivariable Cox models were used to examine how the event
      risk changed with TTR and to compare the high TTR, low TTR, and aspirin-treated
      patients, with TTR being treated as a time-dependent covariate. A total of 2217
      patients were included in the analyses; among whom 1067 were randomized to
      warfarin and 1150 were randomized to aspirin. The median (interquartile range)
      follow-up duration was 3.6 (2.0-5.0) years. Mean (+/-SD) age was 61+/-11.3 years,
      with 80% being men. The mean (+/-SD) TTR was 57% (+/-28.5%). Increasing TTR was
      significantly associated with reduction in primary outcome (adjusted P<0.001),
      death alone (adjusted P=0.001), and improved net clinical benefit (adjusted
      P<0.001). A similar trend was observed for the other 2 outcomes, but significance
      was not reached (adjusted P=0.082 for ischemic stroke and adjusted P=0.109 for
      major hemorrhage). CONCLUSIONS: In patients with heart failure in sinus rhythm,
      increasing TTR is associated with better outcome and improved net clinical
      benefit. Patients in whom good quality anticoagulation can be achieved may
      benefit from the use of anticoagulants. CLINICAL TRIAL REGISTRATION: URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT00041938.

PMID- 25850440
TI  - Short-term effects of espresso coffee on heart rate variability and blood
      pressure in habitual and non-habitual coffee consumers--a randomized crossover
      study.
AB  - OBJECTIVE: Coffee is one of the most widely consumed beverages worldwide. Aim of
      this study was to investigate short-term effects of espresso coffee on heart rate
      variability (HRV), a marker of vagal activity, in healthy habitual and non
      habitual coffee consumers. METHODS: Seventy-seven healthy subjects (38 habitual
      and 39 non-habitual coffee consumers, 74% women, mean age 26.97 +/- 6.88 years)
      took part in three laboratory sessions in a randomized order. In condition 1,
      subjects consumed espresso; in condition 2, subjects consumed decaffeinated
      espresso; and in condition 3, subjects consumed warm water. HRV and blood
      pressure were assessed at rest before and after ingestion of the respective
      beverage. RESULTS: HRV was significantly increased after consumption of
      caffeinated espresso, decaffeinated espresso, or water, indicating increased
      vagal activity in the course of the experiments. In the habitual coffee
      consumers, the increase in vagally mediated HRV was significantly lower after
      consumption of decaffeinated espresso compared to caffeinated espresso. Increases
      of systolic blood pressure were only found in the non-habitual consumers.
      CONCLUSION: We found no evidence for specific short-term effects of caffeinated
      espresso on vagal activity in healthy subjects. Instead, consumption of
      decaffeinated espresso inhibited vagal activity in habitual consumers. This may
      be explained by an attempt of the organism to establish a sympathovagal
      equilibrium comparable to that after caffeine consumption. In the absence of
      caffeine-induced sympathetic activation, this may have been achieved by relative
      vagal withdrawal.

PMID- 25850441
TI  - PARENTAL AND SIBLING MIGRATION AND HIGH BLOOD PRESSURE AMONG RURAL CHILDREN IN
      CHINA.
AB  - This study examines the associations between parental and sibling rural-to-urban
      migration and blood pressure (BP) of rural left-behind children (LBC) in rural
      China. Analysis was based on the 2000, 2004, 2006 and 2009 waves of longitudinal
      data from the China Health and Nutrition Survey, which is an ongoing prospective
      survey covering nine provinces with an individual-level response rate of 88%.
      Blood pressure levels were measured by trained examiners at three consecutive
      times on the same visit and the means of three measurements were used as the
      final BP values. An ordinal BP measure was then created using a recently
      validated age-sex-specified distribution for Chinese children and adolescents,
      distinguishing normal BP, pre-hypertension and hypertension. Random effect
      modelling was performed. Different migration circumstances play different roles
      in LBC's BP with mother-only and both-parent migration being particularly
      detrimental and father-only and sibling-only migration either having no
      association or a negative association with LBC's BP levels or odds of high BP. In
      conclusion, the link between family migration and left-behind children's blood
      pressure is complex, and depends on who is the person out-migrating. 

PMID- 25850439
TI  - Osteoporosis prescribing in long-term care: impact of a provincial knowledge
      translation strategy.
AB  - This study described prescribing trends before and after implementing a
      provincial strategy aimed at improving osteoporosis and fracture prevention in
      Ontario long-term care (LTC) homes. Data were obtained from a pharmacy provider
      for 10 LTC homes in 2007 and 166 homes in 2012. We used weighted, multiple linear
      regression analyses to examine facility-level changes in vitamin D, calcium, and
      osteoporosis medication prescribing rates between 2007 and 2012. After five
      years, the estimated increase in vitamin D, calcium, and osteoporosis medication
      prescribing rates, respectively, was 38.2 per cent (95% confidence interval [CI]:
      29.0, 47.3; p < .001), 4.0 per cent (95% CI: -3.9, 12.0; p = .318), and 0.2 per
      cent (95% CI: -3.3, 3.7; p = .91). Although the study could not assess causality,
      findings suggest that wide-scale knowledge translation activities successfully
      improved vitamin D prescribing rates, although ongoing efforts are needed to
      target homes with low uptake. 

PMID- 25850443
TI  - Fruit-related terms and images on food packages and advertisements affect
      children's perceptions of foods' fruit content.
AB  - OBJECTIVE: To determine whether food label information and advertisements for
      foods containing no fruit cause children to have a false impression of the foods'
      fruit content. DESIGN: In the food label condition, a trained researcher showed
      each child sixteen different food label photographs depicting front-of-food label
      packages that varied with regard to fruit content (i.e. real fruit v. sham fruit)
      and label elements. In the food advertisement condition, children viewed sixteen,
      30 s television food advertisements with similar fruit content and label elements
      as in the food label condition. After viewing each food label and advertisement,
      children responded to the question 'Did they use fruit to make this?' with
      responses of yes, no or don't know. SETTING: Schools, day-care centres, after
      school programmes and other community groups. SUBJECTS: Children aged 4-7 years.
      RESULTS: In the food label condition, chi 2 analysis of within fruit content
      variation differences indicated children (n 58; mean age 4.2 years) were
      significantly more accurate in identifying real fruit foods as the label's
      informational load increased and were least accurate when neither a fruit name
      nor an image was on the label. Children (n 49; mean age 5.4 years) in the food
      advertisement condition were more likely to identify real fruit foods when
      advertisements had fruit images compared with when no image was included, while
      fruit images in advertisements for sham fruit foods significantly reduced
      accuracy of responses. CONCLUSIONS: Findings suggest that labels and
      advertisements for sham fruit foods mislead children with regard to the food's
      real fruit content.

PMID- 25850442
TI  - Biologics in combination with chemotherapy for gastric cancer: is this the
      answer?
AB  - Gastric cancer (GC) continues to be a significant problem worldwide and is the
      third leading cause of cancer death. Armamentarium to treat GC whether it is
      potentially curable or metastatic (incurable) has changed little over the last
      decades with only two new agents being approved (trastuzumab and ramucirumab).
      Many relatively healthy patients after second-line therapy have limited and
      generally ineffective options. The recent The Cancer Genome Atlas analysis has
      uncovered four genotypes of GC; however, it is not sufficient to change our
      treatment strategies and more work needs to be done. The popular front-line
      regimen containing a platinum compound and a fluoropyrimidine is widely used for
      drug development and has worked well globally. Thus, this combination appears
      suitable for adding a biologic agent. The search for new classes of cytotoxics
      has almost stopped, but it is clear that cytotoxic therapy continues to
      contribute and it is here to stay. Biologic agents that modulate the immune
      system of the host appear promising along with many other biologics that can
      potentially inhibit signaling pathways that are often employed by GC cells. We
      will briefly describe the efforts that have targeted EGFR, mTOR, angiogenesis and
      MET pathways. 

PMID- 25850445
TI  - Which Counterfactuals Matter? A Response to Beck.

PMID- 25850444
TI  - A novel NGR-conjugated peptide targets DNA damage responses for
      radiosensitization.
AB  - Radiotherapy is one of the important treatment strategies for patients with
      advanced hepatocellular carcinomas. Developing novel sensitizers for radiotherapy
      is a key issue due to the low intrinsic radiosensitivity of hepatocellular
      carcinomas. It was reported the wild-type NBS1 inhibitory peptide (wtNIP) can
      increase radiosensitivity in several cancer cell lines by abrogating ATM-NBS1
      interaction and interrupting cellular DNA damage response. Here, we developed a
      novel NGRconjugated peptide (NGR-sR9-wtNIP) through coupling the CNGRC angiogenic
      vessel-homing peptide NGR with the wtNIP peptide. Fusion peptide was tested for
      internalization, cytotoxicity in Hep3B cells and for tumor localization, and for
      toxicity in nude mice bearing human hepatocellular carcinomas xenografts. The
      radiosensitizing activity of NGR-sR9-wtNIP was investigated as well. We found
      that NGR-sR9-wtNIP can inhibit irradiation induced NBS1 phosphorylation and
      induce radiosensitization in Hep3B cells. When combined with IR, NGR-sR9-wtNIP
      suppressed tumor growth obviously in xenograft mice. In addition, the fusion
      peptide localized in tumor tissue specifically and barely led to any side effects
      on mice. Taken together, our data strongly suggest that NGRsR9- wtNIP has
      radiosensitizing potential for radiotherapy of hepatocellular carcinomas. 

PMID- 25850446
TI  - Enhanced Colloidal Stability of CeO2 Nanoparticles by Ferrous Ions: Adsorption,
      Redox Reaction, and Surface Precipitation.
AB  - Due to the toxicity of cerium oxide (CeO2) nanoparticles (NPs), a better
      understanding of the redox reaction-induced surface property changes of CeO2 NPs
      and their transport in natural and engineered aqueous systems is needed. This
      study investigates the impact of redox reactions with ferrous ions (Fe2+) on the
      colloidal stability of CeO2 NPs. We demonstrated that under anaerobic conditions,
      suspended CeO2 NPs in a 3 mM FeCl2 solution at pH 4.8 were much more stable
      against sedimentation than those in the absence of Fe2+. Redox reactions between
      CeO2 NPs and Fe2+ lead to the formation of 6-line ferrihydrite on the CeO2
      surfaces, which enhanced the colloidal stability by increasing the zeta potential
      and hydrophilicity of CeO2 NPs. These redox reactions can affect the toxicity of
      CeO2 NPs by increasing cerium dissolution, and by creating new Fe(III)
      (hydr)oxide reactive surface layers. Thus, these findings have significant
      implications for elucidating the phase transformation and transport of redox
      reactive NPs in the environment.

PMID- 25850447
TI  - Mesoporous Ni0.85Se Nanospheres Grown in Situ on Graphene with High Performance
      in Dye-Sensitized Solar Cells.
AB  - Mesoporous Ni0.85Se nanospheres grown on graphene were synthesized via the
      hydrothermal approach. Because of the exceptional electron-transfer pathway of
      graphene and the excellent catalytic ability of the mesoporous Ni0.85Se
      nanospheres, the nanocomposites exhibited excellent electrocatalytic property as
      the counter electrode (CE) of dye-sensitized solar cells. More catalytic active
      sites, better charge-transfer ability and faster reaction velocity of
      Ni0.85Se@RGO (RGO = reduced graphene oxide) CE led to faster and more complete
      I3(-) reduction than Pt, Ni0.85Se, and RGO CEs. Furthermore, the power conversion
      efficiency of Ni0.85Se@RGO CE reached 7.82%, which is higher than that of Pt CE
      (7.54%). Electrochemical impedance spectra, cyclic voltammetry, and Tafel
      polarization were obtained to demonstrate positive synergetic effect between
      Ni0.85Se and RGO, as well as the higher catalytic activity and the better charge
      transfer ability of Ni0.85Se@RGO compared with Pt CE. 

PMID- 25850448
TI  - [Fever with a rash caused by chronic meningococcemia].
AB  - BACKGROUND: Fever with a rash is a common clinical presentation, which can be
      caused by various medical conditions. CASE DESCRIPTION: A 14-year old boy
      presented at the outpatient clinic with a two-week history of fever, myalgia and
      purpuric skin lesions. Blood cultures showed an infection with Neisseria
      meningitidis. After antibiotic treatment, his symptoms resolved promptly.
      CONCLUSION: Chronic meningococcemia is a rare manifestation of meningococcal
      infection and should be considered in patients with prolonged fever, purpuric
      skin lesions and joint involvement.

PMID- 25850449
TI  - [Unexplained neurological dysfunction in the recovery room].
AB  - BACKGROUND: Unexplained neurological dysfunction, which used to be known as
      conversion disorder, is rare following general anaesthesia. This phenomenon is
      difficult to identify in this situation because medically induced dysfunction
      (anaesthesia) turns into unexplained dysfunction. CASE DESCRIPTION: A 58-year-old
      man remained unresponsive to any stimuli for longer than expected following
      uncomplicated surgery under general anaesthesia, although his vital functions
      were normal. It was 2 hours after the operation before a slight eyelid response
      was shown. He then lay motionless in bed for several hours. Complete recovery of
      spontaneous movement and motor functions took 12 hours. No explanation was found.
      CONCLUSION: Unexplained neurological dysfunction can also occur following general
      anaesthesia. The diagnosis is made by neurological assessment. A wait-and-see
      approach is the management policy because the neurological dysfunction disappears
      spontaneously.

PMID- 25850450
TI  - [A man with upper abdominal pain and a pancytopenia].
AB  - A 41-year-old man visited his general practitioner because of upper abdominal
      pain. Physical examination revealed splenomegaly. Laboratory testing showed
      pancytopenia with a striking monocytopenia with hairy cells. Immunological and
      molecular analysis confirmed the diagnosis hairy cell leukemia. 

PMID- 25850451
TI  - [Recurrent upper respiratory tract infections during and after rituximab
      therapy].
AB  - Rituximab maintenance therapy is indicated for the treatment of patients with non
      Hodgkin's lymphoma (NHL) who responded to induction therapy. More than 10% of
      patients will develop rituximab-induced upper respiratory tract infections
      (URTIs). These infections are usually mild in patients receiving first-line or
      second-line treatment. Heavily pretreated patients sometimes undergo additional
      rituximab maintenance therapy. We describe three female patients aged 53, 43 and
      42 years who were successfully treated with rituximab maintenance therapy after
      chemotherapy for three or more recurrences of NHL. These patients developed more
      serious recurrent URTIs due to rituximab-induced long-term
      hypogammaglobulinaemia. In one patient, serum IgG levels continued to decline for
      four years after rituximab therapy. Long-term immunoglobulin substitution was
      needed to treat these patients. Physicians should be aware that URTIs may develop
      in heavily pretreated patients even years after rituximab maintenance therapy and
      substitution with immunoglobulin may be warranted. 

PMID- 25850452
TI  - [A woman with a stepladder deformity of her little finger].
AB  - A 41-year-old woman presented to our emergency department after she tripped over
      a doorstep. Physical examination showed swelling and a stepladder deformity of
      the left little finger. Radiographs confirmed dorsal dislocation in both
      interphalangeal joints. Closed manual reduction under local anaesthesia restored
      position and function of the finger. 

PMID- 25850453
TI  - [Vogt-Koyanagi-Harada syndrome].
AB  - BACKGROUND: Vogt-Koyanagi-Harada syndrome is rare in the Netherlands. However, in
      Asia it is one of the most common causes of panuveitis. The syndrome is
      characterised by a combination of panuveitis, pleocytosis in cerebral spinal
      fluid with or without neurological function loss, alopecia and depigmentation of
      body hair. CASE DESCRIPTION: A 40-year-old male with no previous medical history
      visited the emergency department with unexplained bilateral visual symptoms and
      optic disc swelling. In addition to the latter, further tests only showed
      pleocytosis in cerebral spinal fluid. In the months following the initial
      presentation, vision was restored but the patient developed panuveitis, extensive
      depigmentation, and loss of body hair. On further investigation, the patient
      reported having a great-grandfather from Indonesia. CONCLUSION: Vogt-Koyanagi
      Harada syndrome should be considered in patients of Asian descent presenting with
      panuveitis, alopecia and depigmentation of body hair. Early diagnosis and
      treatment can prevent permanent visual injury.

PMID- 25850454
TI  - [A neonate who could not open her eye].
AB  - We present a case of a female neonate who was born with a string between the
      eyelids of one eye. There were no other dysmorfic features. She had an isolated
      ankyloblepharon filiforme adnatum, a rare congenital malformation of the eyelid. 

PMID- 25850455
TI  - [Early detection of prostate cancer--recommendations after 13 years of follow-up
      in the European randomised study].
AB  - The recent publication of updated results from the European randomised study of
      screening for prostate cancer (ERSPC) with a median 13-year follow-up confirms
      significant relative and absolute reductions in prostate cancer mortality. In
      spite of existing guidelines, Dutch men and professionals remain uncertain about
      the use of PSA testing. The data now available will be helpful in reaching
      informed decisions. In men aged 55-69 years, the relative mortality reduction
      remained similar at 21%; the absolute reduction increased from 0.9 to 1.28 fewer
      deaths/1000 men screened. This translates into much improved figures needing to
      be invited for screening and diagnosed, at 781 and 27 (1410 and 48 in 2009). As
      expected, overall mortality does not differ between the arms of the study. The
      main downside of PSA-driven screening remains the diagnosis of non-life
      threatening cancers (overdiagnosis) by screening, at a frequency of about 40%,
      which can be reduced by use of the Prostate Cancer Risk Calculator. Current data
      support the present guideline which recommends informed decision-making, taking
      into account the advantages and potential damage caused by PSA testing. 

PMID- 25850456
TI  - [Loss of airway after tracheotomy or laryngectomy, an algorithm for practice].
AB  - A 71-year-old man underwent facial reconstructive surgery and a tracheotomy after
      nasal carcinoma. Several hours after surgery, accidental decannulation occurred
      and the patient died because the airway could not be resecured in time. This
      incident led to the implementation of an algorithm for emergency airway
      management in patients with a surgical airway after tracheotomy or laryngectomy.
      All such patients have an information sheet attached to their bed, together with
      the appropriate algorithm. This helps staff to provide care in a standardised
      manner in cases of airway emergency and prevents fixation errors or omission of
      treatment options. 

PMID- 25850457
TI  - [The physician and the collector of diagnoses].
AB  - In the course of the medical curriculum, medical students are trained to
      recognise diagnoses. They classify these in their minds, together with detailed
      information on laboratory and imaging tests, as collections of diagnoses. The
      downside of this could be overdiagnosis. This paper describes some of the faces
      of overdiagnosis. American writer and physician Abraham Verghese eloquently
      describes one of these: the e-doctor looking at a computer screen to see what is
      wrong with the patient, rather than starting with a thorough clinical bedside
      evaluation. Other examples include the finding of small sub-segmental pulmonary
      emboli by increasingly sensitive spiral CT scanning. Finally, this paper
      describes a possible answer to overdiagnosis: prognostic research, notably
      answering questions such as 'what additional diagnostic testing will truly
      improve my patient's prognosis, given their current presentation of signs and
      symptoms?' 

PMID- 25850458
TI  - [Gender differences in cardiac symptoms].
AB  - There is an ongoing discussion as to whether there are gender differences in
      symptom presentation in acute coronary syndromes (ACS). Although the burden of
      coronary artery disease (CAD) and the underlying mechanisms involved in ACS
      differ significantly between the genders during various stages of life,
      researchers seem to persist in comparing women against the standard for male
      patients. This clouds the discussion, and may be potentially harmful to women.
      The female pattern of CAD, with fewer obstructive coronary lesions and relatively
      more vascular dysfunction than in men, translates into a different combination of
      symptoms and relatively more type II ACS. Greater knowledge of gender-sensitive
      cardiology in daily practice would improve recognition and reduce poorer ACS
      outcomes in women. In 2015 the www.eugenmed.eu programme will present a gender
      sensitive 'Roadmap' for cardiology practitioners within the EU. 

PMID- 25850459
TI  - Benzo[d]imidazole Transient Receptor Potential Vanilloid 1 Antagonists for the
      Treatment of Pain: Discovery of trans-2-(2-{2-[2-(4-Trifluoromethyl-phenyl)
      vinyl]-1H-benzimidazol-5-yl}-phenyl)-propan-2-ol (Mavatrep).
AB  - Reported herein is the design, synthesis, and pharmacologic characterization of a
      class of TRPV1 antagonists constructed on a benzo[d]imidazole platform that
      evolved from a biaryl amide lead. This design composes three sections: a 2
      substituted 5-phenyl headgroup attached to the benzo[d]imidazole platform, which
      is tethered at the two position to a phenyl tail group. Optimization of this
      design led to the identification of 4 (mavatrep), comprising a trifluoromethyl
      phenyl-vinyl tail. In a TRPV1 functional assay, using cells expressing
      recombinant human TRPV1 channels, 4 antagonized capsaicin-induced Ca(2+) influx,
      with an IC50 value of 4.6 nM. In the complete Freund's adjuvant- and carrageenan
      induced thermal hypersensitivity models, 4 exhibited full efficacy, with ED80
      values of 7.8 and 0.5 mg/kg, respectively, corresponding to plasma levels of
      270.8 and 9.2 ng/mL, respectively. On the basis of its superior pharmacologic and
      safety profile, 4 (mavatrep) was selected for clinical development for the
      treatment of pain. 

PMID- 25850460
TI  - Migration timing and its determinants for nocturnal migratory birds during autumn
      migration.
AB  - 1. Migration is a common strategy used by birds that breed in seasonal
      environments, and multiple environmental and biological factors determine the
      timing of migration. How these factors operate in combination during autumn
      migration, which is considered to be under weaker time constraints relative to
      spring migration, is not clear. 2. Here, we examine the patterns and determinants
      of migration timing for nocturnal migrants during autumn migration in the north
      eastern USA using nocturnal reflectivity data from 12 weather surveillance radar
      stations and modelled diurnal probability of occurrence for 142 species of
      nocturnal migrants. We first model the capacity of seasonal atmospheric
      conditions (wind and precipitation) and ecological productivity (vegetation
      greenness) to predict autumn migration intensity. We then test predictions,
      formulated under optimal migration theory, on how migration timing should be
      related to assemblage-level estimates of body size and total migration distance
      within the context of dietary guild (insectivore and omnivore) and level of
      dietary plasticity during autumn migration. 3. Our results indicate seasonal
      declines in ecological productivity delineate the beginning and end of peak
      migration, whose intensity is best predicted by the velocity of winds at
      migration altitudes. Insectivorous migrants departed earlier in the season and,
      consistent with our predictions, large-bodied and long-distance insectivorous
      migrants departed the earliest. Contrary to our predictions, large-bodied and
      some long-distance omnivorous migrants departed later in the season, patterns
      that were replicated in part by insectivorous migrants that displayed dietary
      plasticity during autumn migration. 4. Our findings indicate migration timing in
      the region is dictated by optimality strategies, modified based on the breadth
      and flexibility of migrant's foraging diets, with declining ecological
      productivity defining possible resource thresholds during which migration occurs
      when winds at migration altitudes are mild. These observations provide the basis
      to assess how avian migration strategies may be affected by adjustments in
      seasonal patterns of atmospheric circulation and ecological productivity that may
      occur under global climate change.

PMID- 25850461
TI  - Targeting NAMPT for Therapeutic Intervention in Cancer and Inflammation:
      Structure-Based Drug Design and Biological Screening.
AB  - Nicotinamide phosphoribosyltransferase (NAMPT) is a rate limiting enzyme that
      plays an important role in the synthesis of nicotinamide adenine dinucleotide
      (NAD) via a salvage pathway. Along with a role in bioenergetics, NAMPT regulates
      the activity of proteins such as SIRT-1 that utilize NAD as a cofactor. As NAD
      metabolism is usually high in diseased conditions, it has been hypothesized and
      proven that NAMPT is over expressed in various cancers and inflammatory
      disorders. Inhibitors targeting NAMPT could therefore be useful in treating
      disorders arising from aberrant NAMPT signalling. In this study, inhibitors
      against NAMPT were designed using an energy-based pharmacophore strategy and
      evaluated for efficacy in cellular assays. Besides reducing cellular pools of NAD
      and NMN, NAMPT inhibitors decreased concentrations of reactive oxygen species as
      well as mRNA levels of TNFalpha and IL6, thereby implicating their potential in
      alleviating the inflammatory process. In addition, reduced NAD levels
      corroborated with an induction of apoptosis in prostate cancer cell lines. 

PMID- 25850462
TI  - Can blood pressure be lowered safely in older adults with lacunar stroke? The
      Secondary Prevention of Small Subcortical Strokes study experience.
AB  - OBJECTIVES: To determine safety and tolerability of lowering blood pressure in
      older adults with lacunar stroke. DESIGN: Cohort study. SETTING: The Secondary
      Prevention of Small Subcortical Strokes (SPS3) Trial, which compared the efficacy
      of two systolic blood pressure (SBP) targets (<130 mmHg and 130-149 mmHg) for
      secondary stroke prevention. PARTICIPANTS: Of 3,020 SPS3 participants, 494 aged
      75 and older at baseline were used in these analyses. MEASUREMENTS: Rates of side
      effects related to lowering SBP and clinical outcomes, including stroke
      recurrence and vascular death, were examined. RESULTS: Older participants
      achieved SBP levels similar to those of younger participants (mean SBP of 125
      mmHg and 137 mmHg in lower and higher SBP target groups, respectively). At least
      once during the approximately 3.5 years of follow-up, 21% reported dizziness, and
      15% reported lightheadedness when standing; the only significant difference
      between the younger and older groups was unsteadiness when standing (23% vs 32%
      respectively, P < .001). There was no difference according to treatment group. In
      younger adults, recurrent stroke was less likely in the lower than the higher SBP
      group (hazard ratio (HR) = 0.77, 95% confidence interval (CI) = 0.59-1.01) but
      not in older participants (HR = 1.01, 95% CI = 0.59-1.73), although the
      interaction was not significant (P = .39). The lower SBP target was associated
      with a significant reduction in vascular death in older participants (HR = 0.42,
      95% CI = 0.18-0.98), with a significant interaction between age and SBP group (P
      = .049). CONCLUSION: Except for unsteadiness when standing, there was no
      difference according to age in individuals with lacunar stroke with respect to
      side effects potentially related to lowering blood pressure. Although the lower
      SBP target was not associated with lower likelihood of recurrent stroke, these
      exploratory analyses suggested a possible benefit related to vascular death.

PMID- 25850464
TI  - The Code is a chance to lobby for change.
AB  - When we launched our Care campaign in 2012, one of the clear messages was: there
      is no such thing as 'basic' nursing care. We took every opportunity to spread the
      word among politicians and the public that ensuring a patient is clean and
      comfortable and not thirsty or hungry is fundamental care. It goes to the heart
      of what nursing is, and there is nothing basic about it. 

PMID- 25850465
TI  - Trust nurses call for help to tackle new threat to unsocial hours pay.
AB  - Nurses at a large London trust are calling for a cross-union protest against
      attempts to cut unsocial hours pay. 

PMID- 25850463
TI  - Patients' ability to treat anaphylaxis using adrenaline autoinjectors: a
      randomized controlled trial.
AB  - BACKGROUND: Previous work has shown patients commonly misuse adrenaline
      autoinjectors (AAI). It is unclear whether this is due to inadequate training, or
      poor device design. We undertook a prospective randomized controlled trial to
      evaluate ability to administer adrenaline using different AAI devices. METHODS:
      We allocated mothers of food-allergic children prescribed an AAI for the first
      time to Anapen or EpiPen using a computer-generated randomization list, with
      optimal training according to manufacturer's instructions. After one year,
      participants were randomly allocated a new device (EpiPen, Anapen, new EpiPen,
      JEXT or Auvi-Q), without device-specific training. We assessed ability to deliver
      adrenaline using their AAI in a simulated anaphylaxis scenario six weeks and one
      year after initial training, and following device switch. Primary outcome was
      successful adrenaline administration at six weeks, assessed by an independent
      expert. Secondary outcomes were success at one year, success after switching
      device, and adverse events. RESULTS: We randomized 158 participants. At six
      weeks, 30 of 71 (42%) participants allocated to Anapen and 31 of 73 (43%)
      participants allocated to EpiPen were successful - RR 1.00 (95% CI 0.68-1.46).
      Success rates at one year were also similar, but digital injection was more
      common at one year with EpiPen (8/59, 14%) than Anapen (0/51, 0%, P = 0.007).
      When switched to a new device without specific training, success rates were
      higher with Auvi-Q (26/28, 93%) than other devices (39/80, 49%; P < 0.001).
      CONCLUSIONS: AAI device design is a major determinant of successful adrenaline
      administration. Success rates were low with several devices, but were high using
      the audio-prompt device Auvi-Q.

PMID- 25850466
TI  - Student awarded for outstanding care.
AB  - A 27-year-old nursing student was recognised for her care and compassion at a
      prestigious awards ceremony in London attended by HRH The Princess Royal last
      week. 

PMID- 25850467
TI  - Doctor's compassion campaign gathers momentum.
AB  - A campaign begun by a terminally ill doctor to encourage healthcare professionals
      to show more compassion to patients is to go on tour. 

PMID- 25850468
TI  - Record care clearly, accurately and with pride, RCN urges nurses.
AB  - A leading nurse has urged nurses not to view record keeping as 'a chore' but
      rather an integral part of providing compassionate care. 

PMID- 25850469
TI  - Nurses sceptical about two-week discharge target.
AB  - Most nurses in Scotland do not believe the country's new two-week patient
      discharge target will help reduce delays, a survey has found. 

PMID- 25850470
TI  - Court ruling reinforces importance of explaining treatment risks clearly.
AB  - Nurses will need to ensure patients understand the seriousness of their condition
      and the risks associated with proposed treatment as a result of a judgement by
      the UK Supreme Court. 

PMID- 25850471
TI  - Pay rise would address staff shortfall in London.
AB  - A good salary is a significant factor for nurses and they tend to migrate to
      better salaried jobs when choices are available, according to research published
      by the Institute for Fiscal Studies (IFS). 

PMID- 25850472
TI  - Wards' accolades for end of life care.
AB  - Two NHS trusts have become the first to be recognised for the quality of their
      end of life care. 

PMID- 25850473
TI  - Success of Dutch district nursing hard to repeat in UK.
AB  - The UK healthcare system can learn from an innovative nurse-led care service in
      the Netherlands, but using it here could prove a challenge because of
      revalidation, the RCN said. 

PMID- 25850475
TI  - Staff learn the art of handling difficult conversations.
AB  - Nurses in north east England have been learning how best to broach potentially
      difficult conversations with patients as part of a continuing professional
      development programme. 

PMID- 25850476
TI  - Cut agency staff and use money to train nurses, says think tank.
AB  - Boosting nurse training places would save the NHS millions of pounds and improve
      patient safety, a leading think tank has said. 

PMID- 25850477
TI  - Unions put the financial pressures facing nurses in the spotlight.
AB  - NHS employers should contribute to the Nursing and Midwifery Council registration
      fee as nurses continue to feel the pinch, the union Unite plans to tell the NHS
      Pay Review Body. 

PMID- 25850483
TI  - Safe use of medicines.
AB  - Essential facts In England, about 15 million people have a long-term condition -
      a figure that is likely to grow with the ageing population. According to the
      Health Survey for England report, published in December 2014, half of women and
      43% of men in England now regularly take prescription drugs, with statins,
      analgesics and antidepressants among the most common. Many long-term conditions
      are managed with medicines, but it is estimated that 30-50% of prescribed
      medication is not taken as intended. 

PMID- 25850484
TI  - 'It's rare that a prisoner has one problem'.

PMID- 25850486
TI  - Spiritual solace without religion.

PMID- 25850485
TI  - Ensuring we get the fundamentals right.

PMID- 25850494
TI  - Sugarscience.
AB  - Sugarscience was developed by health scientists from the University of California
      to provide an authoritative, evidence-based resource about sugar and its effects
      on health. 

PMID- 25850497
TI  - NHS quit smoking.
AB  - NHS Quit Smoking is the official app for the NHS Smokefree campaign. It is
      designed to be a companion app for the first 28 days of giving up smoking, and
      uses motivational messages, progress timelines and financial calculations to
      encourage quitters. 

PMID- 25850498
TI  - The best of the week's health-related TV and radio.

PMID- 25850499
TI  - A chance to give people with learning disabilities a voice.
AB  - The green paper unveiled last week by care minister Norman Lamb is a first step
      to legally entitling people with learning disabilities to comment on, or even
      challenge, their care. 

PMID- 25850500
TI  - Evidence shows high-calibre nurses are an investment in safety.
AB  - James Smith is critical of June Clark's argument for mandatory nurse-patient
      ratios (letters March 25), citing a single study published in the Journal of
      Advanced Nursing. The study by Schreuders et al found no consistent association
      between nurse staffing levels and a variety of complications in Western
      Australian hospitals. 

PMID- 25850501
TI  - Revalidation is a great idea, but what resources will support it?
AB  - I welcome revalidation and love the film at rcni.com/workplace/revalidation ,
      which I have shared with my colleagues. 

PMID- 25850502
TI  - The money spent on revalidation could have been put to better use.
AB  - I qualified as a nurse in 1983 and have continuously developed my skills and
      knowledge. I have a yearly performance review with my line manager, for which I
      am required to provide evidence of my practice development. 

PMID- 25850503
TI  - Financial pressures should not force students out of nursing.
AB  - I was pleased to hear of the petition by nursing student Katherine Webb calling
      on the health secretary to increase the bursary for nursing students (News April
      1). 

PMID- 25850507
TI  - Experiences of military nurses in Iraq and Afghanistan.
AB  - Since 2001 military nurses have successfully supported military operations in
      deployed field hospitals in both Iraq and Afghanistan. These deployments have
      presented unique challenges for military nurses. This article reviews the
      literature on the experience of nurses during these deployments and, using a
      thematic analysis approach, aims to understand their experience. The results
      provide an insight into the lives of military nurses who served in Iraq and
      Afghanistan and highlight some of the coping strategies adopted by nurses in
      conflict situations. The discussion outlines the key themes and, using excerpts
      from the literature, explores the challenges and coping strategies used. 

PMID- 25850508
TI  - Mixed methods research.
AB  - Mixed methods research involves the use of qualitative and quantitative data in a
      single research project. It represents an alternative methodological approach,
      combining qualitative and quantitative research approaches, which enables nurse
      researchers to explore complex phenomena in detail. This article provides a
      practical overview of mixed methods research and its application in nursing, to
      guide the novice researcher considering a mixed methods research project. 

PMID- 25850509
TI  - Prevention and management of constipation in adults.
AB  - Constipation is a common, often chronic, condition that is a health concern for
      providers of care. The condition can be distressing and although seldom life
      threatening can lead to patient discomfort and debilitating effects on patients'
      quality of life. Initial management of chronic constipation should include
      lifestyle changes and increased fibre and fluids. More active interventions
      include the use of laxatives and other medications, irrigation and biofeedback
      therapy. Some patients may require surgery. This article provides an overview of
      the strategies used to prevent constipation in adults as well as the possible
      treatment options available. 

PMID- 25850510
TI  - Fluoride.
AB  - A recent conversation with a colleague prompted me to read this CPD article on
      fluoride. She told me my tea drinking might have health benefits in the form of
      increased fluoride intake. 

PMID- 25850511
TI  - A passion for research.
AB  - My decision to be a research student arose from my desire to add something new to
      the body of knowledge about the experiences of older people from black and
      minority ethnic (BME) backgrounds in hospital. 

PMID- 25850512
TI  - Notice board.
AB  - Courses, events, grants, and awards to progress your career. 

PMID- 25850513
TI  - Making an objective assessment.
AB  - Personal independence payments (PIP) replaced disability living allowance from
      April 2013, with companies Capita and Atos carrying out assessments in England
      and Wales on behalf of the Department of Work and Pensions (DWP). Nurses play a
      key role in PIP assessments. 

PMID- 25850514
TI  - Inspection and improvement.
AB  - The mention of Care Quality Commission (CQC) inspections can strike anxiety into
      healthcare staff, but CQC national professional adviser Rona McCandlish says that
      the CQC is about 'assisting and supporting quality improvement'. 

PMID- 25850515
TI  - Student life - ask us what we think.
AB  - Students are in the best position to recognise the qualities of effective nurse
      educators. With this in mind, we asked students on the Bachelor of Science in
      Nursing (BScN) course what makes a good teacher in the clinical practice setting.

PMID- 25850516
TI  - Functional analysis of truncated forms of ETV6.

PMID- 25850517
TI  - Neutrophil activation by Candida glabrata but not Candida albicans promotes
      fungal uptake by monocytes.
AB  - Candida albicans and Candida glabrata account for the majority of candidiasis
      cases worldwide. Although both species are in the same genus, they differ in key
      virulence attributes. Within this work, live cell imaging was used to examine the
      dynamics of neutrophil activation after confrontation with either C. albicans or
      C. glabrata. Analyses revealed higher phagocytosis rates of C. albicans than C.
      glabrata that resulted in stronger PMN (polymorphonuclear cells) activation by C.
      albicans. Furthermore, we observed differences in the secretion of chemokines,
      indicating chemotactic differences in PMN signalling towards recruitment of
      further immune cells upon confrontation with Candida spp. Supernatants from co
      incubations of neutrophils with C. glabrata primarily attracted monocytes and
      increased the phagocytosis of C. glabrata by monocytes. In contrast, PMN
      activation by C. albicans resulted in recruitment of more neutrophils. Two
      complex infection models confirmed distinct targeting of immune cell populations
      by the two Candida spp.: In a human whole blood infection model, C. glabrata was
      more effectively taken up by monocytes than C. albicans and histopathological
      analyses of murine model infections confirmed primarily monocytic infiltrates in
      C. glabrata kidney infection in contrast to PMN-dominated infiltrates in C.
      albicans infection. Taken together, our data demonstrate that the human
      opportunistic fungi C. albicans and C. glabrata are differentially recognized by
      neutrophils and one outcome of this differential recognition is the preferential
      uptake of C. glabrata by monocytes. 

PMID- 25850518
TI  - The lived experience of fathers of preterm infants in the Neonatal Intensive Care
      Unit: a systematic review of qualitative studies.
AB  - AIMS AND OBJECTIVES: To systematically review the experience of fathers of
      preterm infants hospitalised in the Neonatal Intensive Care Unit. BACKGROUND:
      Family-centred care is more and more acknowledged in Neonatal Intensive Care
      Units, advocating for active engagement of both parents in the care journey.
      Nonetheless, fathers' Neonatal Intensive Care Unit experience has received
      limited research attention. DESIGN: Systematic review of qualitative studies.
      METHODS: Four electronic databases (CINHAL, ISI Web of Science, PubMed, Scopus)
      were explored and studies published between 2000-2014 were included. Preferred
      Reporting Item for Systematic Reviews and Meta-analysis (PRISMA) and Joanna
      Briggs Institute (JBI) Critical Appraisal Tool for Qualitative Studies guidelines
      were adopted. Key themes were extracted and synthesised. RESULTS: Five main
      themes resuming fathers' experience of preterm birth and Neonatal Intensive Care
      Unit stay were identified from 14 studies. Themes were: emotional roller-coaster,
      paternal needs, coping strategies, self-representation and caregiving engagement.
      These dimensions were found to be dynamically shaped across three critical
      turning points: preterm birth, Neonatal Intensive Care Unit stay and at home.
      CONCLUSIONS: Neonatal Intensive Care Unit fathers of preterm infants experience
      ambivalence, a set of different needs and coping strategies. They modify their
      self-representations along the Neonatal Intensive Care Unit journey and needs
      specific nursing support and intervention to sustain caregiving engagement and
      transition to parenthood. RELEVANCE TO CLINICAL PRACTICE: A systematic and
      deepened understanding of preterms' fathers lived experience in Neonatal
      Intensive Care Unit would be helpful to inform nursing practice. Specific action
      priorities are suggested within the frame of family-centred care.

PMID- 25850519
TI  - Relationship between maternal pre-pregnancy body mass index, gestational weight
      gain and childhood fatness at 6-7 years by air displacement plethysmography.
AB  - This study aims to investigate the effect of maternal pre-pregnancy body mass
      index (BMI) and gestational weight gain (GWG) on offspring body composition. In
      this prospective cohort study, offspring body composition at 6 years of age was
      obtained through air displacement plethysmography. Linear regression was used to
      obtain crude and adjusted coefficients. Information regarding offspring body
      composition and maternal pre-pregnancy BMI was available for 3156 children and on
      offspring body composition and GWG for 3129 children. There was a direct
      association of maternal pre-pregnancy BMI and GWG with offspring's fat mass (FM),
      fat-free mass (FFM), fat mass index (FMI), fat-free mass index (FFMI) and body
      fat percent (BF%) in crude and adjusted analyses. After adjustment for co
      variables, for each kg m(-2) of maternal pre-pregnancy BMI increase, there was a
      mean increment of 0.13 kg in the offspring FFM, 0.06 kg m(-2) in FFMI, 0.11 kg in
      FM, 0.07 kg m(-2) in FMI and 0.18% in BF%. For each kilogram of maternal GWG
      increase, there was a mean increment of 0.08 kg in offspring's FM, 0.05 kg m(-2)
      in FMI, 0.04 kg in FFM, 0.01 kg m(-2) in FFMI and 0.18 % in BF%. Mothers with a
      higher pre-pregnancy BMI or GWG tend to have children with greater adiposity at
      age 6 years. Fetal overnutrition is more likely among mothers with greater BMI
      during pregnancy; as a consequence, it can accelerate the childhood obesity
      epidemic. 

PMID- 25850520
TI  - Time to surgery for hip fracture patients in a rural orthopaedic referral
      hospital.
AB  - PROBLEM: It is well established that shorter surgical waiting time for hip
      fracture patients improves outcomes. We identify and quantify time to surgery for
      hip fracture patients in a rural hospital. DESIGN: Retrospective observational
      study. SETTING:  : A sixty-bed rural referral hospital with an orthopaedic
      service. Data were collected for 57 patients 50 years and older who had surgery
      for Muller AO type 31-A and 31-B fractures at Bega Hospital in 2012. KEY MEASURES
      FOR IMPROVEMENT: Time to surgery from presentation was compared for patients who
      presented directly to Bega hospital to those that were transferred from a
      peripheral hospital. STRATEGIES FOR CHANGE: To quantify contributing factors to
      surgical delay will help identify areas for future improvement. EFFECTS OF
      CHANGE: Delay to surgery from presentation was significantly greater for
      transferred patients (58 hours), compared with direct presentations (41 hours).
      Mean time for patient transfer was 23 hours. Thirty-five per cent of patients had
      their operation within 36 hours from presentation. LESSONS LEARNT: The time to
      surgery for most transfer and direct presentation patients fell outside current
      guidelines. In our geographically large referral network, delay to surgery was
      significantly influenced by time to transfer. Based on previously published
      research, surgery for our hip fracture patients should be expedited. We therefore
      recommend priority transfer for these significantly injured patients and
      dedicated emergency operating lists to perform this surgery in a timely manner.

PMID- 25850521
TI  - Prevalence of diabetes mellitus and prediabetes in the adult Romanian population:
      PREDATORR study.
AB  - BACKGROUND: The PREDATORR (PREvalence of DiAbeTes mellitus, prediabetes,
      overweight, Obesity, dyslipidemia, hyperuricemia and chronic kidney disease in
      Romania) study is the first national study analyzing the prevalence of diabetes
      mellitus (DM) and prediabetes, and their association with cardiometabolic,
      sociodemographic, and lifestyle risk factors in the Romanian population aged 20
      79 years. METHODS: This was an epidemiological study with a stratified, cross
      sectional, cluster random sampling design. Sociodemographic, lifestyle, and
      anamnestic data were collected through self- and interviewer-administered
      questionnaires, and biochemical assays and oral glucose tolerance tests were
      performed. RESULTS: In all, 2728 participants from 101 clinics of general
      practitioners were randomly selected, with a probability proportional to
      population size according to the 2002 Romanian Census. The participation rate was
      99.6%. Impaired glucose regulation (prediabetes, known and unknown DM) was found
      in 28.1% of the study population. The overall age- and sex-adjusted prevalence of
      DM was 11.6% (95% CI 9.6%-13.6%), of which 2.4% (95% CI 1.7%-3.1%) had unknown
      DM. The prevalence of DM increased with age and was higher in men than in women.
      The age- and sex-adjusted prevalence of prediabetes was 16.5% (95%CI 14.8%
      18.2%), with the highest percentage in the 60-79 year age group and in women.
      Obesity, abdominal obesity, dyslipidemia, low education level, and a family
      history of diabetes were associated with glucose metabolism disorders.
      CONCLUSIONS: The PREDATORR study shows a high prevalence of impaired glucose
      regulation in the adult Romanian population, providing data on the prevalence of
      DM and prediabetes and their association with several risk factors.

PMID- 25850522
TI  - Intracerebral hemorrhage at young age: long-term prognosis.
AB  - BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) is a devastating disorder
      associated with dismal outcomes. The long-term mortality and functional outcome
      of ICH in young patients was studied - areas so far poorly investigated. METHODS:
      A follow-up study was performed on a cohort of patients. Clinical and imaging
      data on ICH patients aged 16-49 were retrospectively obtained and linked with a
      nationwide cause-of-death register. The modified Rankin Scale (mRS) was evaluated
      for 30-day survivors at a visit 9.7 (7.0-12.0) years after ICH onset. Independent
      factors associated with mortality and unfavorable functional outcome (mRS 2-5)
      were sought by multivariate analysis. RESULTS: Amongst the 268 1-month survivors,
      1-year survival was 98.1% [95% confidence interval (CI) 96.2%-100%], 5-year
      survival 93.2% (89.3%-97.1%) and 10-year survival 88.8% (84.9%-92.7%). After
      adjustment for age and intraventricular hematoma extension, male sex [odds ratio
      (OR) 3.36, 95% CI 1.28-8.80] and diabetes (OR 2.64, 1.01-6.89) were associated
      with increased mortality. Unfavorable functional outcome emerged in 49%. After
      adjustment for confounders, age (OR 1.09 per 1 year, 95% CI 1.03-1.15), initial
      stroke severity (1.17 per one National Institutes of Health Stroke Scale score
      point, 1.08-1.27) and intraventricular hemorrhage (3.26, 1.11-9.55) were
      associated with unfavorable functional outcome. CONCLUSIONS: Of every 10
      survivors of acute phase ICH at a young age, one died within 10 years after
      onset, male sex and diabetes being associated with increased mortality. Half the
      survivors did not achieve a favorable functional outcome, which was predicted by
      increasing age, initial stroke severity and intraventricular hemorrhage.

PMID- 25850523
TI  - Concurrent Cardioversion of Atrial Fibrillation during ICD Shock Testing.
AB  - BACKGROUND: Many patients receiving an implantable cardioverter-defibrillator
      (ICD) also have atrial fibrillation (AF). Shock testing during ICD implantation
      carries a potential risk of cardioversion to sinus rhythm (SR) and thrombembolic
      events. We aimed to analyze the recurrence of AF after cardioversion to SR during
      ICD shock testing. METHODS: A total of 555 consecutive patients referred to a
      tertiary hospital in Switzerland for ICD implantation or generator exchange
      between 02/2002 and 03/2010 were screened for AF. Fifty-seven patients who were
      in AF at the time of ICD shock testing were included. RESULTS: Forty-four
      patients (77%) were successfully cardioverted from AF to SR. Type of AF
      (persistent, not permanent 64 vs 31% of cardioverted patients) was the only
      predictor. Thirty-nine patients (89%) experienced a recurrence of AF/atrial
      flutter after a median of 54 days (interquartile range 35-251 days). The only
      predictor for recurrence of AF was previous AF declared as permanent. No ischemic
      stroke occurred during hospitalization for the procedure. CONCLUSIONS: For
      patients in AF undergoing shock testing at the time of ICD implant, there is a
      high chance of cardioversion from AF to SR, but there is also a high risk of
      early recurrence. Decisions regarding long-term anticoagulation should not be
      based on the heart rhythm immediately following shock testing.

PMID- 25850524
TI  - Positive and negative bioimprinted polymeric substrates: new platforms for cell
      culture.
AB  - Bioimprinting, which involves capturing cell morphological details into a polymer
      matrix, provides a new class of patterned surfaces which opens an opportunity to
      investigate how cells respond to their own signatures and may introduce
      possibilities for regulating their behaviour. In this study, phenotypic details
      of human nasal chondrocytes (HNCs) were replicated in soft polydimethylsiloxane
      (PDMS) mould resulting in inverse replicas of cells, which have been termed here
      as 'negative bioimprint'. For the first time, the information from this negative
      bioimprint was then transferred into another PDMS layer resulting in surfaces
      which resemble cell morphology and were called 'positive bioimprints'. Soft
      lithography was used to transfer these details from PDMS into different polymers
      like polystyrene, tissue culture polystyrene and clinically used block co-polymer
      poly (ethylene glycol) terephthalate-poly (butylene terephthalate) (PEGT-PBT).
      Results obtained from surface characterization confirmed that fine details of
      cells were successfully replicated from cells to different polymer matrices
      without any significant loss of information during the different steps of pattern
      transfer. HNCs seeded on different polymer surfaces with positive and negative
      bioimprints exhibited distinct behaviour. Cells cultured on positive bioimprints
      were more spread out and displayed high levels of proliferation compared to those
      on negative bioimprints, where cells were more compact with lower proliferation.

PMID- 25850525
TI  - Reduction in Endogenous Insulin Secretion is a Risk Factor of Sarcopenia in Men
      with Type 2 Diabetes Mellitus.
AB  - Sarcopenia has recently attracted widespread attention, because it increases
      risks of fall and bedridden. Although patients with type 2 diabetes mellitus
      (T2DM) are known to have lower muscle mass of limbs than healthy people, the
      mechanism is still unclear. We thus examined the association of muscle mass with
      parameters of endogenous insulin secretion such as fasting immunoreactive
      insulin, fasting C-peptide immunoreactivity (CPR), and daily urine CPR in 191 men
      with T2DM. Muscle mass of arms and legs was evaluated by dual-energy X-ray
      absorptiometry, and we calculated relative skeletal muscle index (RSMI), which is
      useful for the diagnosis of sarcopenia. Multiple regression analyses adjusted for
      age, duration of T2DM, serum creatinine, HbA1c, and insulin-like growth factor-I
      showed that each parameter of endogenous insulin was significantly and positively
      correlated with muscle mass of arms and legs as well as RSMI (p < 0.05).
      Moreover, logistic regression analyses adjusted for confounding factors mentioned
      above showed that each parameter of endogenous insulin was significantly lower in
      subjects with sarcopenia than those without it (p < 0.05). In conclusion,
      reduction in endogenous insulin secretion is an independent risk factor of
      sarcopenia in men with T2DM.

PMID- 25850526
TI  - The facile realization of luminescence based on one yellow emissive four
      coordinate organoboron material.
AB  - The orange emissive powders of a boron-containing compound generate red, green,
      and blue luminescence after compressing, heating, and volatile acid fuming,
      respectively. Thus, stimulus-induced emissions have been facilely realized based
      on one organic pi-conjugated material for the first time, to the best of our
      knowledge. 

PMID- 25850527
TI  - Effective practical management of patients with atrial fibrillation when using
      new oral anticoagulants.
AB  - Practical management of stroke prevention in patients with non-valvular atrial
      fibrillation (AF) requires physicians to find the optimal balance between
      maximizing prevention of ischaemic stroke and minimizing the risk of bleeding.
      Vitamin K antagonists have traditionally been used for stroke prevention in
      patients with AF; however, they have been associated with increased risk of
      bleeding, particularly intracranial haemorrhage. New oral anticoagulants (OACs)
      have shown similar efficacy to the vitamin K antagonist warfarin but with a
      reduced risk of bleeding, particularly life-threatening bleeding such as
      intracranial haemorrhage. Decisions about which new OAC therapy to use may be
      influenced by patient characteristics such as age, renal function, co-medication
      use, and bleeding risk. This review uses a case-based approach to highlight the
      practical management issues to be considered by the physician when selecting a
      new OAC for stroke prevention in patients with non-valvular AF. 

PMID- 25850528
TI  - Mirror therapy enhances upper extremity motor recovery in stroke patients.
AB  - The purpose of this study was to evaluate the effects of mirror therapy program
      in addition with physical therapy methods on upper limb recovery in patients with
      subacute ischemic stroke. 15 subjects followed a comprehensive rehabilitative
      treatment, 8 subjects received only control therapy (CT) and 7 subjects received
      mirror therapy (MT) for 30 min every day, five times a week, for 6 weeks in
      addition to the conventional therapy. Brunnstrom stages, Fugl-Meyer Assessment
      (upper extremity), the Ashworth Scale, and Bhakta Test (finger flexion scale)
      were used to assess changes in upper limb motor recovery and motor function after
      intervention. After 6 weeks of treatment, patients in both groups showed
      significant improvements in the variables measured. Patients who received MT
      showed greater improvements compared to the CT group. The MT treatment results
      included: improvement of motor functions, manual skills and activities of daily
      living. The best results were obtained when the treatment was started soon after
      the stroke. MT is an easy and low-cost method to improve motor recovery of the
      upper limb.

PMID- 25850529
TI  - Fibular strut graft for humeral aneurysmal bone cyst with varus deformity.
AB  - PURPOSE: Proximal humerus is a common site for ABC and frequently associated with
      varus deformity that limits shoulder abduction. A prospective study was conducted
      to evaluate the use of intramedullary non-vascularised autogenous fibular strut
      graft for reconstruction without internal fixation. METHODS: A total of 20
      patients (12 girls, 8 boys) were managed for proximal humeral ABC with varus
      deformity by extended curettage, osteotomy, intramedullary fibular graft and
      composite bone substitute. Their ages ranged from 10 to 17 years (average, 13.3
      years). The lesion was juxtaphyseal in 16 patients and metaphyseal in 4. All
      cysts were active and centrally located type 2. The modified Enneking scoring
      system was used for final functional evaluation. Radiological assessment was done
      for the extent of defect healing, incorporation of the fibula and correction of
      the deformity. RESULTS: After a mean follow-up of 41.2 months (range, 24-74) most
      of patients were satisfied and resumed daily activities without pain and with
      good range of shoulder movement. One patient complained of shoulder pain 10
      months after surgery and was attributed to local recurrence. Limitation of
      recreational activity was experienced by one patient. There were no cases of deep
      infection, nerve deficit or pathological fracture. No cases of failed healing or
      incorporation of the fibula was detected. The improved shoulder abduction was
      closely related to the mean correction of the neck shaft angle. CONCLUSIONS: The
      technique is proved to be effective in controlling disease, correcting deformity
      and improving function.

PMID- 25850530
TI  - How to explain the role of magnetic resonance imaging on evaluating tumour
      response of osteosarcoma to neoadjuvant chemotherapy: authors' reply.

PMID- 25850532
TI  - Influence of different factors on the nitrogenase activity of the engineered
      Escherichia coli 78-7.
AB  - The engineered Escherichia coli 78-7 is a derivative of E. coli JM109 carrying a
      nitrogen fixation (nif) gene cluster composed of nine genes (nifB, nifH, nifD,
      nifK, nifE, nifN, nifX, hesA and nifV) and its own sigma(70)-dependent nif
      promoter from a gram-positive bacterium Paenibacillus sp. WLY78. The
      physiological and biochemical characteristics of the engineered E. coli 78-7 were
      analyzed by using Biolog GEN III MicroPlate, with E. coli JM109 and
      JM109/pHY300PLK (E. coli JM109 carrying empty vector) as controls. Analysis of 94
      phenotypic tests: 71 carbon source utilization assays and 23 chemical sensitivity
      tests showed that the engineered E. coli 78-7, E. coli JM109 and JM109/pHY300PLK
      gave similar patterns of utilization of various substrates as carbon and energy
      sources. Furthermore, the effect of carbon source, nitrogen source, culture
      temperature on the nitrogenase activity of the engineered E. coli 78-7 was
      investigated. Our study demonstrates that the nif capacity of E. coli 78-7 was
      affected significantly by the different culture condition. The significant
      nitrogenase activity of E. coli 78-7 were obtained when cells were cultivated in
      the medium containing 4 g/l glucose (carbon source) and 2 mM glutamate (nitrogen
      source) and at 30  degrees C.

PMID- 25850531
TI  - Living standard is related to microregional differences in stroke characteristics
      in Central Europe: the Budapest Districts 8-12 Project.
AB  - OBJECTIVES: To test whether str oke features relate to living standard within one
      city by comparing 2 districts. METHODS: District-8 (D-8) ranks the last, whereas
      District-12 (D-12) is the second regarding personal monthly income of the 23
      districts of Budapest, Hungary. Stroke cases hospitalized in 2007 were identified
      by the database of the National Health Insurance Fund and postal codes for living
      address. Case certification was performed by personal visits to the general
      practitioners. Demographic data, risk factors and survival status in 2010 were
      analyzed using the anonymized database. RESULTS: Three-year case fatality was
      36.6 % in D-8 and 31.5 % in D-12 (p = 0.24). Of the fatal cases, men were more
      than 12 years younger in D-8 than in D-12 (69.2 +/- 13.3 vs. 82.4 +/- 9.2 years,
      p < 0.001). Men died younger than women in D-8 (69.2 +/- 13.3 vs. 75.2 +/- 12.4;
      p = 0.036), but not in D-12 (82.4 +/- 9.2 vs. 81.9 +/- 7.3, p = 0.8). Non-treated
      hypertension, alcohol dependence, and smoking were significantly more prevalent
      in the poor district (p < 0.01 for all). CONCLUSION: In national stroke programs
      of former Eastern Block countries, primary prevention should focus especially on
      male populations of less wealthy regions.

PMID- 25850533
TI  - Cloning, expression, characterization and mutational analysis of the tfdA gene
      from Cupriavidus campinensis BJ71.
AB  - 2,4-Dichlorophenoxyacetic acid (2,4-D)/alpha-ketoglutarate (alpha-KG) dioxygenase
      (TfdA) is an Fe(II)-dependent enzyme that catalyzes the first step in degradation
      of the herbicide 2,4-D. Previous studies focused on the tfdA gene in Ralstonia
      eutropha JMP134 isolated in Australia. In this study, a new tfdA gene was cloned
      from Cupriavidus campinensis BJ71, an effective degrading bacteria from China,
      based on the iCOnsensus-DEgenerate Hybrid Oligonucleotide Primers (iCODEHOPs)
      protocol, combined with high-efficiency Thermal Asymmetric Interlaced PCR (hiTAIL
      PCR). The open reading frame of 861 bp encoded a putative 287 amino acid protein
      with a theoretical molecular mass of 32.32 kDa. The gene was overexpressed in
      Escherichia coli BL21 (DE3) and the purified TfdA showed optimal activity at pH
      6.75 and 30  degrees C. This enzyme was more thermostable and it could use 3
      hydrocinnamic acid as substrate, with a similar enzyme activity compared with 2,4
      D. TfdA and its variants were created as maltose-binding protein (MBP) tagged
      fusion proteins to examine the roles of putative substrate-binding residues. The
      MBP-N110A, MBP-V198A and MBP-R207K proteins showed decreased k cat and increased
      Km, and MBP-R278A was inactive, suggesting these residues may affect 2,4-D
      binding or catalysis. 

PMID- 25850534
TI  - Aromatase inhibitors in male breast cancer: a pooled analysis.
AB  - Although several studies have shown the efficacy of third-generation aromatase
      inhibitors (AIs) in women with breast cancer, the role of such molecules remains
      elusive in male breast cancer patients. It is also unknown whether the addition
      of gonadotropin-releasing hormone (GnRH) analogues to AIs would be a superior
      strategy or not. This pooled analysis was conducted in accordance with the PRISMA
      guidelines. All studies that examined the efficacy of AIs in metastatic male
      breast cancer were considered eligible. Overall, 15 studies (105 cases) were
      eligible for this pooled analysis. The mean age of the study sample was 62.8
      years. ER status was positive in all eligible cases. AI was given as first line
      in 61.5 % of cases. GnRH analogue was co-administered with AI in 37.1 % of cases
      (n = 39). CR, PR, SD and PD were achieved in 5.7, 23.8, 37.2 and 33.3 % of cases,
      respectively. The median PFS and OS were equal to 10.0 and 39.0 months,
      respectively. Co-administration of GnRH analogues was associated with more than
      threefold increase in rates of clinical benefit (OR = 3.37, 95 % CI 1.30-8.73)
      but did not seem to correlate with better PFS or OS. No statistically significant
      associations between the examined outcomes and the other parameters were noted.
      Available data suggest that AIs may potentially play a promising role in the
      optimal therapeutic strategy for metastatic male breast cancer patients.
      Especially, co-administration of AI with a GnRH analogue seems to increase the
      rate of clinical benefit and could be more effective, warranting further
      consideration. 

PMID- 25850535
TI  - Comparison of multi-frequency bioimpedance with perometry for the early detection
      and intervention of lymphoedema after axillary node clearance for breast cancer.
AB  - The importance of early detection of lymphoedema by arm volume measurements
      before surgery and repeated measurements after surgery in women undergoing
      axillary node clearance (ANC) in order to enable early intervention is
      recognised. A prospective multi-centre study was performed which studied the
      difference between multi-frequency bioimpedance electrical analysis (BIS) and
      perometer arm measurement in predicting the development of lymphoedema. Women
      undergoing ANC underwent pre-operative and regular post-operative measurements of
      arm volume by both methods. The primary endpoint is the incidence of lymphoedema
      (>=10 % arm volume increase compared to contralateral arm by perometer) at 2 and
      5 years after ANC. The threshold for intervention in lymphoedema was also
      assessed. Out of 964 patients recruited, 612 had minimum 6 months follow-up data.
      Using 1-month post-operative measurements as baseline, perometer detected 31
      patients with lymphoedema by 6 months (BIS detected 53). By 6 months, 89 % of
      those with no lymphoedema reported at least one symptom. There was moderate
      correlation between perometer and BIS at 3 months (r = 0.40) and 6 months (r =
      0.60), with a sensitivity of 73 % and specificity of 84 %. Univariate and
      multivariate analyses revealed a threshold for early intervention of >=5 to <10 %
      (p = 0.03). Threshold for early intervention to prevent progression to
      lymphoedema is >=5 to <10 % but symptoms alone do not predict lymphoedema. The
      modest correlation between methods at 6 months indicates arm volume measurements
      remain gold standard, although longer term follow-up is required. 

PMID- 25850536
TI  - Erratum to: Incidence of BRCA1 and BRCA2 non-founder mutations in patients of
      Ashkenazi Jewish ancestry.
AB  - In Table 2 of the original publication, the HGVS and legacy nomenclature were
      mismatched and the HGVS nomenclature did not correlate with data listed in the
      table. The corrected table is listed below.

PMID- 25850537
TI  - Psychometric Evaluation of a Consumer-Developed Family-Centered Care Assessment
      Tool.
AB  - The objective of this study was to create a psychometrically sound measure of
      family-centered care, the Family-Centered Care Assessment (FCCA), developed
      through a process led by families in collaboration with maternal and child health
      leaders. The items for the FCCA scale were initially developed by families of
      children and youth with special needs in partnership with pediatric providers and
      researchers. Using an Institutional Review Board-approved research protocol, the
      questions were revised based on input from focus groups of diverse parents in
      three states. Parental responses (N = 790) to the revised 59-item survey were
      collected online from families in 49 states. Item distributions uniformly showed
      excellent spread. A principal axes factor analysis confirmed the existence of a
      single factor. Rasch modeling item analyses identified a reduced subset of 24
      items that demonstrated excellent psychometric properties. All items met the
      criteria for a linear Rasch scale. Empirical evidence in support of the construct
      validity of the 24-item measure was derived: all items had a positive and
      substantial item-total correlation; person alpha scale reliability was >0.80 and
      the item reliability was >0.90; both separation indices were >2.0; infit and
      outfit statistics were within 0.5-1.5; and item difficulties ranged between -2
      and +2 logits. Strong rank-ordered associations and large effect sizes were
      observed for six indicators of quality of care. This study's family-led process
      produced a tool, the FCCA, to measure families' experience of care with excellent
      psychometric properties.

PMID- 25850539
TI  - Is diabetes a hypercoagulable state? A critical appraisal.
AB  - Diabetes mellitus (DM), a chronic disease with an increasing incidence and
      prevalence worldwide, is an established risk factor for arterial cardiovascular,
      cerebrovascular and peripheral vascular diseases including acute myocardial
      infarction, stroke and peripheral artery disease. On the other hand, its role as
      independent risk factor for venous thromboembolism (VTE) and for cardioembolic
      stroke or systemic embolism (SE) in patients with atrial fibrillation (AF) is
      more conflicting. Venous and arterial thromboses have traditionally been regarded
      as separate diseases, but recent studies have documented an association between
      these vascular complications. Cardiovascular risk factors may contribute to
      unprovoked VTE, and VTE may be an early symptomatic event in patients at high
      cardiovascular risk, including diabetic patients. Compelling evidences suggest
      that DM is associated with a higher risk of development and progression of AF.
      Furthermore, in AF patients with a coexisting DM the risk of cardioembolic
      stroke/SE appeared increased. Thus, DM has been included as one of the items of
      the CHADS2 score and of the subsequent CHA2DS2-VASc score that have been
      developed to assess the arterial tromboembolic risk of AF patients. Such a high
      incidence of thromboembolic events observed in these clinical subsets may be
      attributable to the DM-related prothrombotic state due to a number of changes in
      primary and secondary hemostasis. Although of potential clinical interest,
      unfortunately, to date, no study has properly evaluated the effects of drugs used
      to control blood glucose levels on the risk of venous thromboembolism and
      arterial cardioembolic events in patients with DM. 

PMID- 25850540
TI  - Focal muscle vibration as a possible intervention to prevent falls in elderly
      women: a pragmatic randomized controlled trial.
AB  - BACKGROUNDS: Different and new approaches have been proposed to prevent the risk
      of falling of elderly people, particularly women. AIMS: This study investigates
      the possibility that a new protocol based on the focal mechanical muscle
      vibration may reduce the risk of falling of elderly women. METHODS: A pragmatic
      randomized controlled triple-blind trial with a 6-month follow-up after
      intervention randomized 350 women (mean age 73.4 years + 3.11), members of local
      senior citizen centers in Rome, into two groups: vibrated group (VG) and control
      group (CG). For VG participants a mechanical vibration (lasting 10 min) was
      focally applied on voluntary contracted quadriceps muscles, three times a day
      during three consecutive days. CG subjects received a placebo vibratory
      stimulation. Subjects were tested immediately before (T0) and 30 (T1) and 180
      (T2) days after the intervention with the Performance-Oriented Mobility
      Assessment (POMA) test. All subjects were asked not to change their lifestyle
      during the study. CG underwent sham vibratory treatment. RESULTS: While CG did
      not show any statistically significant change of POMA at T1 and T2, VG revealed
      significant differences. At T2, ~47% of the subjects who completed the study
      obtained the full score on the POMA test and ~59% reached the full POMA score.
      CONCLUSIONS: The new protocol seems to be promising in reducing the risk of
      falling of elderly subjects.

PMID- 25850541
TI  - Multi-muscle coordination during a challenging stance.
AB  - PURPOSE: This study aimed to identify the muscle synergies during standing under
      various sensory contexts in healthy young adults. METHODS: Sixteen healthy young
      adults participated in this study. The 4-min stance task was conducted under
      vision (eyes open or eyes closed) and proprioception (standing on ground or
      narrowed blocks) manipulated contexts. Electromyography (EMG) of 8 muscles around
      the right side of the trunk and leg were recorded and submitted to principal
      component analysis (PCA) to extract the muscle synergies. Two-way ANOVA with
      repeated measures was employed to test the effect of sensory contexts on the
      muscle synergies. RESULTS: PCA extracted three muscle synergies that accounted
      for the variance of standing EMG, including the push-back (composed of medial
      gastrocnemius, vastus medialis and biceps femoris), push-forward (composed of
      tibialis anterior and rectus femoris) and proximal mixed (composed of rectus
      abdominis, rector spinae, rectus femoris and biceps femoris) synergies. Block
      standing increased the contribution of the push-back synergy while decreased the
      contribution of the push-forward synergy. In addition, contribution of the
      proximal mixed synergy was higher under ground-standing with eyes open than under
      block-standing with eyes open. CONCLUSION: Three muscle synergies were identified
      during standing in healthy young adults, and the synergies were affected by
      proprioception but not visual disturbance. The push-back and push-forward
      synergies showed the opposite response to proprioceptive disturbance, which may
      result from their antagonism role. Whether this control regime is used for
      elderly adults or patient populations with movement disorder needs to be further
      investigated.

PMID- 25850542
TI  - [Identification of seniors at risk--primary care: a validated questionnaire
      predicting functional decline].
AB  - OBJECTIVES: To modify and validate in primary healthcare the Identification of
      Seniors At Risk (ISAR) screening questionnaire to identify older persons at
      increased risk of functional decline and to compare this strategy with risk
      stratification by age alone. STUDY DESIGN AND SETTING: Prospective development
      (n=790) and validation cohorts (n=2,573) of community-dwelling persons aged >=70
      years. Functional decline at 12 months was defined as an increase of at least one
      point on the modified Katz-activities of daily living index score compared with
      baseline or death. RESULTS: Three items were independently associated with
      functional decline: age (odds ratio [OR] 1.06 per year; 95% confidence interval
      [CI] 1.02, 1.10) dependence in instrumental activities of daily living (OR: 2.17;
      95% CI: 1.46, 3.22), and impaired memory (OR: 2.22; 95% CI: 1.41, 3.51). The area
      under the receiver operating characteristics curve (AUC) range of the ISAR
      primary care model was 0.67-0.70 and 40.6% was identified at increased risk.
      Validation yielded an AUC range of 0.63-0.64. Age>=75 years alone yielded an AUC
      range of 0.56-0.57 and identified 65.0% at increased risk in the validation
      cohort. CONCLUSION: Although the ISAR-Primary Care (ISAR-PC) has moderate
      predictive value, application of the ISAR-PC is more efficient than selection
      based on age alone in identifying persons at increased risk of functional
      decline. This paper is a translated and adjusted version based on a publication
      in Journal of Clinical Epidemiology, 67 (2014) 1121-1130.

PMID- 25850543
TI  - Environmentally Realistic Doses of Cadmium as a Possible Etiologic Agent for
      Idiopathic Pathologies.
AB  - Cadmium is a heavy metal of increasing environmental concern that has long been
      associated to several human pathological processes. Recent population surveys
      have correlated cadmium non-occupational exposure to widespread idiopathic
      pathologies. Food and tobacco are reported to be the main exposure sources of
      cadmium to the general population, as phosphate fertilizers are rich in such a
      metal, thus contaminating the crops. Although its mechanisms of toxicity are not
      a consensus in the literature, it is well established that reactive oxygen
      species play a key role in this process, leading to the oxidation of several
      biological molecules. We have therefore assessed whether three environmentally
      realistic doses of cadmium alter the oxidative status of Wistar rat testis and
      eventually result in histological damages. Our results show that even the lowest
      environmental dose of cadmium was able to disturb the endogenous antioxidant
      system in Wistar testis, although an increase in lipid peroxidation was observed
      only within the group exposed to the highest environmental dose. Despite that no
      remarkable morphological changes were observed in any group, significant
      alterations in blood vessel lumen were reported for some cadmium-exposed animals,
      suggesting that endothelium is one of the primary targets involved in cadmium
      toxicity. 

PMID- 25850544
TI  - Arsenic-Induced Antioxidant Depletion, Oxidative DNA Breakage, and Tissue Damages
      are Prevented by the Combined Action of Folate and Vitamin B12.
AB  - Arsenic is a grade I human carcinogen. It acts by disrupting one-carbon (1C)
      metabolism and cellular methyl (-CH3) pool. The -CH3 group helps in arsenic
      disposition and detoxification of the biological systems. Vitamin B12 and folate,
      the key promoters of 1C metabolism were tested recently (daily 0.07 and 4.0 MUg,
      respectively/100 g b.w. of rat for 28 days) to evaluate their combined efficacy
      in the protection from mutagenic DNA-breakage and tissue damages. The selected
      tissues like intestine (first-pass site), liver (major xenobiotic metabolizer)
      and lung (major arsenic accumulator) were collected from arsenic-ingested (0.6
      ppm/same schedule) female rats. The hemo-toxicity and liver and kidney functions
      were monitored. Our earlier studies on arsenic-exposed humans can correlate
      carcinogenesis with DNA damage. Here, we demonstrate that the supplementation of
      physiological/therapeutic dose of vitamin B12 and folate protected the rodents
      significantly from arsenic-induced DNA damage (DNA fragmentation and comet assay)
      and hepatic and renal tissue degeneration (histo-architecture, HE staining). The
      level of arsenic-induced free-radical products (TBARS and conjugated diene) was
      significantly declined by the restored actions of several antioxidants viz.
      urate, thiol, catalase, xanthine oxidase, lactoperoxidase, and superoxide
      dismutase in the tissues of vitamin-supplemented group. The alkaline phosphatase,
      transaminases, urea and creatinine (hepatic and kidney toxicity marker), and
      lactate dehydrogenase (tissue degeneration marker) were significantly impaired in
      the arsenic-fed group. But a significant protection was evident in the vitamin
      supplemented group. In conclusion, the combined action of folate and B12 results
      in the restitution in the 1C metabolic pathway and cellular methyl pool. The
      cumulative outcome from the enhanced arsenic methylation and antioxidative
      capacity was protective against arsenic induced mutagenic DNA breakages and
      tissue damages. 

PMID- 25850545
TI  - Expression of Iodotyrosine Deiodinase in Thyroid and Other Organs in Iodine
      Deficient and Iodine-Excess Rats.
AB  - In mammals, iodothyronine deiodinase and iodotyrosine deiodinase (IYD) are known
      to catalyze the reductive dehalogenation. IYD is a critical enzyme in maintaining
      iodine homeostasis. Advances in the study of iodothyronine deiodinase have been
      published steadily; research on IYD has been slow on its function and regulation.
      We studied the expression of IYD in thyroid, liver, and kidney in conditions such
      as iodine deficiency and excess to determine its regulation and role in iodine
      recycling. Sixty 4-week-old female Wistar rats were randomly divided into two
      groups, with each group containing three subgroups. The rats were fed with
      different iodine intake for 3 months. After 3 months, all the rats were
      sacrificed, and the expression of IYD in thyroid, liver, and kidney of the rats
      were determined. We found that the expression of thyroidal IYD in 0.3-fold-iodine
      intake group was significantly higher as compared with the low-iodine feed
      control group (p < 0.01), whereas the expression in 6-fold-iodine intake group
      was significantly decreased as compared with normal-iodine feed control group (p
      < 0.01). However, the variation of IYD expression in thyroid was not similar to
      liver and kidney. In conclusion, iodine deficiency results in an increased
      expression of IYD in thyroid, whereas excess iodine decreases the expression of
      thyroidal IYD. In humans, daily iodine intake of <75 or >500 MUg can affect the
      expression of thyroidal IYD. The safety range of iodine intake is narrow. In
      addition, further investigations are required to study the expression and
      regulation of IYD in various organs.

PMID- 25850546
TI  - A practical approach to avoiding iatrogenic Creutzfeldt-Jakob disease (CJD) from
      invasive instruments.
AB  - Potential Creutzfeldt-Jakob disease instrument-contamination events continue to
      occur, causing widespread hospital and patient concern. We propose the use of a
      combination of diagnostic tests (ie, spinal fluid for 14-3-3 protein or nasal
      brushing for misfolded prion protein) and instrument handling procedures (ie,
      using a regional set of dedicated instruments), which if applied to all patients
      admitted with symptoms of either dementia or cerebellar disease, should eliminate
      the risk of iatrogenic instrument infection.

PMID- 25850548
TI  - Prostate cancer: New biomarker panel prognosticates patient survival.

PMID- 25850549
TI  - Intermediate-stage HCC--upfront resection can be feasible.

PMID- 25850550
TI  - Immunotherapy: CheckMate--has nivolumab beaten melanoma?

PMID- 25850551
TI  - Lung cancer: Implementing lung-cancer screening--oncological 'grey areas'.

PMID- 25850552
TI  - Intermediate-stage HCC--upfront resection can be feasible.

PMID- 25850554
TI  - Surgical issues in patients with breast cancer receiving neoadjuvant
      chemotherapy.
AB  - Early randomized trials of the addition of neoadjuvant chemotherapy (NACT) to the
      treatment regimen of patients with breast cancer failed to demonstrate an
      improvement in overall survival compared with conventional adjuvant therapy;
      nevertheless, the increased opportunities for breast conservation, owing to
      downstaging of the primary tumour, and enthusiasm regarding the potential to
      tailor systemic therapy based on responses observed in the neoadjuvant setting,
      resulted in the adoption of this approach as a useful clinical tool. That the
      effectiveness of NACT varies by molecular subtype is becoming increasingly clear,
      and although the potential of tailoring adjuvant systemic therapy based on
      treatment response before surgery remains to be realized, the increasing rates of
      pathological complete response following NACT have had a considerable impact on
      locoregional treatment considerations. For example, NACT reduces the need for
      mastectomy and axillary lymph-node dissection, thus decreasing the morbidity of
      surgery, without compromising outcomes. However, selection of the ideal
      candidates for preoperative chemotherapy remains critical, and personalizing
      local therapy based on the degree of response is the subject of ongoing clinical
      trials. This article reviews the current issues surrounding surgery of the breast
      and axilla in patients with breast cancer receiving NACT.

PMID- 25850555
TI  - Production of bacteriocin-like inhibitory substance by Bifidobacterium lactis in
      skim milk supplemented with additives.
AB  - Bacteriocins are natural compounds used as food biopreservatives instead of
      chemical preservatives. Bifidobacterium animalis subsp. lactis (Bifid. lactis)
      was shown to produce a bacteriocin-like inhibitory substance (BLIS) able to
      inhibit the growth of Listeria monocytogenes selected as an indicator
      microorganism. To enhance this production by the strain Bifid. lactis BL 04, skim
      milk (SM) was used as a fermentation medium either in the presence or in the
      absence of yeast extract, Tween 80 or inulin as stimulating additives, and the
      results in terms of bacterial growth and BLIS production were compared with those
      obtained in a traditional high cost complex medium such as Man, Rogosa and Sharpe
      (MRS). To this purpose, all the cultivations were carried out in flasks at 200
      rpm under anaerobic conditions ensured by a nitrogen flowrate of 1.0 L/min for 48
      h, and BLIS production was quantified by means of a modified agar diffusion assay
      at low values of both temperature and concentration of List. monocytogenes.
      Although all these ingredients were shown to exert positive influence on BLIS
      production in both media, yeast extract and SM were by far the best ingredient
      and the best medium, respectively, allowing for a BLIS production at the late
      exponential phase of 2000 AU/ml.

PMID- 25850557
TI  - Effectiveness and Mechanisms of Defluorination of Perfluorinated Alkyl Substances
      by Calcium Compounds during Waste Thermal Treatment.
AB  - The mineralization of perfluorinated alkyl substances (PFASs) by calcium
      compounds during the waste thermal treatment was systemically studied. Different
      calcium compounds showed different mineralization efficiencies of PFASs during
      the thermal process, owing to the different reaction mechanisms. Calcium
      hydroxide was recommended as the most effective Ca reagent for PFAS
      defluorination because the carbon-fluorine bonds in PFASs can be converted to
      carbon-hydrogen bonds via the hydrodefluorination reaction. PFASs with different
      chain lengths and functional groups were further investigated for their
      potentially different mineralization behavior. The results showed that the chain
      length of PFASs had an insignificant effect on the mineralization efficiency by
      calcium hydroxide. The thermogravimetric analysis-differential thermal analysis
      (TGA-DTA) also revealed that perfluorooctanesulfonate (PFOS) and
      perfluorohexanesulfonate (PFHxS) (with different chain lengths) had a similar
      thermal behavior. However, PFASs with different functional groups showed
      different mineralization behavior with calcium hydroxide in relation to their
      different thermal decomposition temperatures. Finally, the mineralization ratio
      of polytetrafluoroethylene (PTFE) particles by calcium hydroxide could reach 80%
      or higher when the temperature was above 400  degrees C. The gas
      chromatography/mass spectrometry (GC/MS) results demonstrated much reduced
      production of gaseous fluorocarbon fragments during PTFE decomposition when
      coexisting with calcium hydroxide. 

PMID- 25850553
TI  - Targeting Notch, Hedgehog, and Wnt pathways in cancer stem cells: clinical
      update.
AB  - During the past decade, cancer stem cells (CSCs) have been increasingly
      identified in many malignancies. Although the origin and plasticity of these
      cells remain controversial, tumour heterogeneity and the presence of small
      populations of cells with stem-like characteristics is established in most
      malignancies. CSCs display many features of embryonic or tissue stem cells, and
      typically demonstrate persistent activation of one or more highly conserved
      signal transduction pathways involved in development and tissue homeostasis,
      including the Notch, Hedgehog (HH), and Wnt pathways. CSCs generally have slow
      growth rates and are resistant to chemotherapy and/or radiotherapy. Thus, new
      treatment strategies targeting these pathways to control stem-cell replication,
      survival and differentiation are under development. Herein, we provide an update
      on the latest advances in the clinical development of such approaches, and
      discuss strategies for overcoming CSC-associated primary or acquired resistance
      to cancer treatment. Given the crosstalk between the different embryonic
      developmental signalling pathways, as well as other pathways, designing clinical
      trials that target CSCs with rational combinations of agents to inhibit possible
      compensatory escape mechanisms could be of particular importance. We also share
      our views on the future directions for targeting CSCs to advance the clinical
      development of these classes of agents. 

PMID- 25850558
TI  - Outcomes of delayed total hip arthroplasty in patients with a previous
      ipsilateral acetabular fracture.
AB  - Post-traumatic arthritis of the hip can develop in 12-57% of patients after an
      acetabular fracture. Once it develops, salvage treatment options include
      arthroplasty or arthrodesis. Delayed total hip arthroplasty (THA) has been shown
      to be a viable treatment option to decrease pain, improve stability and increase
      functional outcomes. Using cemented designs, earlier long-term studies reported
      satisfactory functional outcomes of delayed THA used to treat previously failed
      acetabular fractures. However, high aseptic loosening rates were also observed.
      Recent advances in cementless acetabular designs have shown comparable functional
      outcomes and loosening rates compared to those undergoing THA for non-traumatic
      arthritis. However, even with improvements in functional and radiographic
      outcomes, unique complications are commonly encountered in patients with previous
      acetabular fractures, including heterotopic bone around the hip, increased
      operative times and blood loss, aseptic loosening, sciatic nerve injury and
      dislocation. The outcomes and complications of delayed THA in patients with
      previous acetabular fracture will be reviewed. 

PMID- 25850559
TI  - Geleophysic dysplasia: a novel in-frame deletion of a tandem repeat in the
      ADAMTSL2 gene.

PMID- 25850560
TI  - Intake of energy-dense snack foods and drinks among Dutch children aged 7-12
      years: how many, how much, when, where and which?
AB  - OBJECTIVE: To describe the energy-dense snack food (EDSF) and energy-dense drink
      (EDD) consumption of children in the Netherlands and investigate subgroup
      differences. The amounts consumed, eating occasions, places of consumption and
      consumed types are reported. DESIGN: Twenty-four hour dietary recall data were
      used to describe the EDSF and EDD consumption. Subgroup differences concerning
      these intakes were identified with ANCOVA. SETTING: Dutch National Food
      Consumption Survey 2007-2010. SUBJECTS: Children (n 860) aged 7-12 years.
      RESULTS: The mean number of EDSF events was 3.3 (sd 1.6) per day, yielding 1569.7
      (sd 928.7) kJ. Average EDD consumption was 594.2 (sd 342.3) ml/d, yielding 737.2
      (sd 495.9) kJ. Over 90 % of the children consumed more energy from non-core foods
      per day than recommended. Differences in EDSF and EDD consumption were found
      between several subgroups. Most importantly, we found higher intakes among older
      children and children with low educated mothers. Almost half of the EDSF events
      took place in the afternoon and at home. Cookies and sweets were consumed during
      half of the EDSF events. Almost one-third of the EDD were consumed in the
      afternoon. The majority of these drinks were consumed at home and most were soft
      drinks. CONCLUSIONS: The results demonstrate that snack food and drink
      consumption is highly prevalent among Dutch children. Health promotion efforts
      addressing these behaviours are warranted and the present study could accelerate
      these initiatives. Focusing on children with low educated parents and on snacking
      at home after school offers the greatest potential to reduce snack food and drink
      intakes.

PMID- 25850561
TI  - The maturation of research into the avian hippocampal formation: Recent
      discoveries from one of the nature's foremost navigators.
AB  - For more than 30 years, a growing number of researchers have been attracted to
      the challenge of understanding the neurobiological organization of the avian
      hippocampal formation (HF) and its relationship to the remarkable spatial
      cognitive abilities of birds. In this selective review, we highlight recent
      anatomical and developmental findings that reveal a HF design that defies any
      simple comparison to the mammalian hippocampus and leaves unanswered the
      seemingly enduring question of whether a dentate gyrus homologue is to be found
      in HF. From a functional perspective, we highlight the recent discoveries that
      implicate HF in the use of space for memory pattern segregation and continued
      interest in the role HF neurogenesis may play in supporting memory function and
      its relationship to memory decline in aging birds. We also summarize data that
      nurture a fundamental reinterpretation of the role of HF in spatial cognition by
      suggesting HF involvement in spatial perception antecedent to any memory
      formation. Given the disproportionate adaptive significance of space for birds,
      which has led to the evolution of their exceptional navigational and memory
      abilities, there is little doubt that the avian HF will continue to provide
      important and unexpected insights into the neural basis of spatial cognition.

PMID- 25850562
TI  - Short-term population-based non-linear concentration-response associations
      between fine particulate matter and respiratory diseases in Taipei (Taiwan): a
      spatiotemporal analysis.
AB  - Fine particulate matter <2.5 MUm (PM2.5) has been associated with human health
      issues; however, findings regarding the influence of PM2.5 on respiratory disease
      remain inconsistent. The short-term, population-based association between the
      respiratory clinic visits of children and PM2.5 exposure levels were investigated
      by considering both the spatiotemporal distributions of ambient pollution and
      clinic visit data. We applied a spatiotemporal structured additive regression
      model to examine the concentration-response (C-R) association between children's
      respiratory clinic visits and PM2.5 concentrations. This analysis was separately
      performed on three respiratory disease categories that were selected from the
      Taiwanese National Health Insurance database, which includes 41 districts in the
      Taipei area of Taiwan from 2005 to 2007. The findings reveal a non-linear C-R
      pattern of PM2.5, particularly in acute respiratory infections. However, a PM2.5
      increase at relatively lower levels can elevate the same-day respiratory health
      risks of both preschool children (<6 years old) and schoolchildren (6-14 years
      old). In preschool children, same-day health risks rise when concentrations
      increase from 0.76 to 7.44 MUg/m(3), and in schoolchildren, same-day health risks
      rise when concentrations increase from 0.76 to 7.52 MUg/m(3). Changes in PM2.5
      levels generally exhibited no significant association with same-day respiratory
      risks, except in instances where PM2.5 levels are extremely high, and these
      occurrences do exhibit a significant positive influence on respiratory health
      that is especially notable in schoolchildren. A significant high relative rate of
      respiratory clinic visits are concentrated in highly populated areas. We
      highlight the non-linearity of the respiratory health effects of PM2.5 on
      children to investigate this population-based association. The C-R relationship
      in this study can provide a highly valuable alternative for assessing the effects
      of ambient air pollution on human health.

PMID- 25850563
TI  - T-DNA insertion in aquaporin gene AtPIP1;2 generates transcription profiles
      reminiscent of a low CO2 response.
AB  - Results from CO2 diffusion studies and characterization of Arabidopsis thaliana
      aquaporin AtPIP1;2 T-DNA insertion lines support the idea that specific
      aquaporins facilitate the diffusion of CO2 through biological membranes. However,
      their function as CO2 diffusion facilitators in plant physiology is still a
      matter of debate. Assuming that a lack of AtPIP1;2 causes a characteristic
      transcriptional response, we compared data from a AtPIP1;2 T-DNA insertion line
      obtained by Illumina sequencing, Affymetrix chip analysis and quantitative RT-PCR
      to the transcriptome of plants grown under drought stress or under low CO2
      conditions. The plant reaction to the deficit of AtPIP1;2 was unlike drought
      stress responses but comparable with that of low CO2 conditions. In addition, we
      observed a phenotype characteristic to plants grown under low CO2 . The findings
      support the hypothesis that the AtPIP1;2 function in plant physiology is not to
      facilitate water but CO2 diffusion.

PMID- 25850564
TI  - Antagonistic effect of helpers on breeding male and female survival in a
      cooperatively breeding bird.
AB  - 1. Cooperatively breeding species are typically long lived and hence, according
      to theory, are expected to maximize their lifetime reproductive success through
      maximizing survival. Under these circumstances, the presence of helpers could be
      used to lighten the effort of current reproduction for parents to achieve higher
      survival. 2. In addition, individuals of different sexes and ages may follow
      different strategies, but whether male and female breeders and individuals of
      different ages benefit differently from the presence of helpers has often been
      overlooked. Moreover, only one study that investigated the relationship between
      parental survival and the presence of helpers used capture-mark-recapture
      analyses (CMR). These methods are important since they allow us to account for
      the non-detection of individuals that are alive in the population but not
      detected, and thus, the effects on survival and recapture probability to be
      disentangled. 3. Here, we used multi-event CMR methods to investigate whether the
      number of helpers was associated with an increase in survival probability for
      male and female breeders of different ages in the sociable weaver Philetairus
      socius. In this species, both sexes reduce their feeding rate in the presence of
      helpers. We therefore predicted that the presence of helpers should increase the
      breeders' survival in both sexes, especially early in life when individuals
      potentially have more future breeding opportunities. In addition, sociable weaver
      females reduce their investment in eggs in the presence of helpers, so we
      predicted a stronger effect of helpers on female than male survival. 4. As
      expected we found that females had a higher survival probability when breeding
      with more helpers. Unexpectedly, however, male survival probability decreased
      with increasing number of helpers. This antagonistic effect diminished as the
      breeders grew older. 5. These results illustrate the complexity of fitness costs
      and benefits underlying cooperative behaviours and how these may vary with the
      individuals' sex and age. They also highlight the need for further studies on the
      sex-specific effects of helpers on survival.

PMID- 25850565
TI  - Disseminated histoplasmosis as pseudo Richter's transformation in a patient with
      chronic lymphocytic leukemia.

PMID- 25850567
TI  - Microscale Sensing of Oxygen via Encapsulated Porphyrin Nanofibers: Effect of
      Indicator and Polymer "Core" Permeability.
AB  - Biomimetic polymer nanofibers integrate sensing capabilities creating utility
      across many biological and biomedical applications. We created fibers consisting
      of either a poly(ether sulfone) (PES) or a polysulfone (PSU) core coated by a
      biocompatible polycaprolactone (PCL) shell to facilitate cell attachment. Oxygen
      sensitive luminescent probes Pt(II) meso-tetra(pentafluorophenyl)porphine
      (PtTFPP) or Pd(II) meso-tetra(pentafluorophenyl)porphine (PdTFPP), were
      incorporated in the core via single-step coaxial electrospinning providing
      superior sensitivity, high brightness, linear response, and excellent stability.
      Both PES-PCL and PSU-PCL fibers provide more uniform probe distribution than
      polydimethylsiloxane (PDMS). PSU-based sensing fibers possessed optimum
      sensitivity due to their relatively higher oxygen permeability. During exposure
      to 100% nitrogen and 100% oxygen, PES-PCL fiber displayed an I0/I100 value of
      6.7; PSU-PCL exhibited a value of 8.9 with PtTFPP as the indicator. In contrast,
      PdTFPP-containing fibers possess higher sensitivity due to the long porphyrin
      lifetime. The corresponding I0/I100 values were 80.6 and 106.7 for the PES-PCL
      and PSU-PCL matrices, respectively. The response and recovery times were
      0.24/0.39 s for PES-PCL and 0.38/0.83 s for PSU-PCL which are 0.12 and 0.11 s
      faster, respectively, than the Pt-based porphyrin in the same matrices.
      Paradoxically, lower oxygen permeabilities make these polymers better suited to
      measuring higher (i. e., ~20%) oxygen contents than PDMS. Individual fiber
      sensing was studied by fluorescence spectrometry and at a sub-micrometer scale by
      total internal reflection fluorescence (TIRF). Specific polymer blends relate
      polymer composition to the resulting sensor properties. All compositions
      displayed linear Stern-Volmer plots; sensitivity could be tailored by matrix or
      the sensing probe selection. 

PMID- 25850566
TI  - Flaxseed reduces the pro-carcinogenic micro-environment in the ovaries of normal
      hens by altering the PG and oestrogen pathways in a dose-dependent manner.
AB  - The objective of the present study was to find the optimum dose of flaxseed that
      would decrease PG and alter oestrogen pathway endpoints implicated in ovarian
      cancer. In the study, four groups of fifty 1.5-year-old chickens were fed
      different amounts of flaxseed (0, 5, 10 or 15% of their total diet) for 4 months
      and were then killed to collect blood and tissues. Levels of flaxseed lignan
      metabolites, Enterolactone (EL) and Enterodiol (ED) were measured in the serum,
      liver and ovaries by liquid chromatography-MS/MS, and n-3 and n-6 fatty acid (FA)
      levels were measured by GC. The effects of the varied flaxseed doses were
      assessed by measuring levels of PGE2 and oestrogen metabolites (16-hydroxyestrone
      (16-OHE1) and 2-hydroxyestrone (2-OHE1)) as well as by analysing the expression
      of the oestradiol metabolising enzymes CYP3A4 (cytochrome p450, family 3,
      subfamily A, polypeptide 4), CYP1B1 (cytochrome p450, family 1, subfamily B,
      polypeptide 1) and CYP1A1 (cytochrome p450, family 1, subfamily A, polypeptide 1)
      and that of oestrogen receptor alpha (ERalpha) in the ovaries. The ratio of n-3:n
      FA increased with an increase in flaxseed supplementation and corresponded to a
      dose-dependent decrease in cyclo-oxygenase-2 protein and PGE2 levels. EL and ED
      increased in the serum, liver and ovaries with increased concentrations of
      flaxseed. Flaxseed decreased the expression of ERalpha in the ovaries. The ratio
      of 2-OHE1:16-OHE1 in the serum increased significantly in the 15% flaxseed diet,
      and there was a corresponding increase in CYP1A1 in the liver and decrease in
      CYP3A4 in the ovaries. CYP1B1 mRNA also decreased with flaxseed diet in the
      ovaries. The 15% flaxseed-supplemented diet significantly decreased inflammatory
      PGE2, ERalpha, CYP3A4, CYP1B1 and 16-OHE1, but it increased CYP1A1 and 2-OHE1,
      which thus reduced the inflammatory and pro-carcinogenic micro-environment of the
      ovaries.

PMID- 25850568
TI  - Number of active electrodes at time of staged tined lead interstim implant does
      not impact clinical outcomes.
AB  - OBJECTIVES: To determine: (1) if obtaining motor response on <4 tined lead
      electrodes at time of placement affects subjective and objective clinical outcome
      and (2) voltage requirements to elicit motor response at implant and first
      postoperative visit number based on number of responding electrodes. METHODS: We
      reviewed our prospective neuromodulation database to identify patients with
      unilateral S3 lead placement and motor response (bellows +/- toe flexion) on
      stimulation of 1-4 electrodes, then grouped by number of active electrodes at
      lead placement. Stage 1 success, reoperation and reprogramming rates, mean
      voltage at implant and first postoperative visit, and Interstitial Cystitis
      Symptom/Problem Indices (ICSI-PI) were analyzed using Pearson's Chi-square,
      Fisher's exact, Kruskal-Wallis or Wilcoxon rank tests. RESULTS: Two hundred forty
      four patients met inclusion criteria, categorized into 1-2 (n = 25), 3 (n = 48),
      and 4 active electrodes (n = 171). There were no significant differences between
      groups in terms of age, indications for neuromodulation, or stage 1 success. At
      implant, patients with <4 active electrodes required higher mean voltages for
      motor responses (5.9, 4.9, and 3.9 volts for each group respectively; P <
      0.0001). Mean voltages for sensory threshold at first postoperative programming
      were 1.5 +/- 1.5, 0.9 +/- 1.0, and 0.8 +/- 1.0, respectively (P = 0.08). Overall
      reoperation rates, and reprogramming sessions at 24 months did not differ (P =
      0.72 and P = 0.50). ICSI-PI scores improved similarly in all groups. CONCLUSIONS:
      Motor response on four electrodes is not necessary for successful stage 1 trial.
      Despite higher voltage requirements in those with <4 active electrodes at
      implant, this difference was not observed at initial postoperative programming.
      Neurourol. Urodynam. 35:625-629, 2016. (c) 2015 Wiley Periodicals, Inc.

PMID- 25850570
TI  - Is there an association between metabolic syndrome and cognitive function in very
      old adults? The Newcastle 85+ Study.
AB  - OBJECTIVES: To determine, using data from the Newcastle 85+ Study, whether there
      is an association between modern diagnostic criteria for metabolic syndrome
      (MetS) and cognitive function in very old adults (>=85) and whether inflammation,
      physical activity, or diabetes mellitus status affects this association. DESIGN:
      Longitudinal, population-based cohort study. SETTING: Newcastle and North
      Tyneside, United Kingdom. PARTICIPANTS: Community-dwelling and institutionalized
      men and women recruited through general practices (N = 845). MEASUREMENTS: MetS
      was defined according to the National Cholesterol Education Program (NCEP) Adult
      Treatment Panel III (ATP III) criteria. Cross-sectional and prospective (up to 5
      years of follow-up) associations between MetS and global cognitive function
      (assessed using the Mini-Mental State Examination (MMSE)) and between MetS and
      attention and episodic memory (assessed using the Cognitive Drug Research
      battery) were performed. RESULTS: MetS was not associated with cognitive function
      at baseline or cognitive change over time. Lack of association was not because
      MetS was predictive of subsequent mortality. Of the individual components of the
      MetS criteria, high blood pressure was associated with better cognitive function
      at baseline (MMSE: beta (standard error (SE)) = -0.716 (0.152), P < .001), and
      low high-density lipoprotein cholesterol was associated with poorer global
      cognitive function at baseline (MMSE: 0.436 (0.131), P = .001). CONCLUSION: The
      association between MetS and cognitive decline, which has been described in
      younger populations (<75), was not apparent in this population of individuals
      aged 85 and older at baseline.

PMID- 25850571
TI  - Applications of yeast-based signaling sensor for characterization of antagonist
      and analysis of site-directed mutants of the human serotonin 1A receptor.
AB  - The monoamine neurotransmitter serotonin (5-HT) regulates a wide spectrum of
      human physiology through the 5-HT receptor family. One such receptor, the 5-HT1A
      receptor (HTR1A), is the most widely studied subtype and represents a significant
      molecular target in medicinal and therapeutic fields. Yeast-based fluorescent
      reporter systems have proven to be especially useful for GPCR assays, since
      detection using a fluorescent reporter considerably simplifies measurement
      procedures. However, previously reported systems using enhanced green fluorescent
      protein (EGFP) as the reporter in yeast still showed low signal-to-noise (S/N)
      ratios, making EGFP difficult to apply as an easily accessible tool. Therefore,
      we constructed a refined yeast-based GPCR biosensor employing a high-sensitivity
      strain that incorporated both a Galpha-engineered receptor and a fluorescent
      reporter (ZsGreen). As we report here, the refined yeast-based fluorescent
      biosensor was applied successfully to antagonist characterization and analysis of
      site-directed mutants of the HTR1A receptor. Pindolol, a known antagonist of
      HTR1A, specifically inhibited agonist-induced signaling, demonstrating the ease
      of evaluating inhibition effects using our reporter strain. Characterization of
      site-specific receptor mutants confirmed the role of specific targeted residues,
      including the highly conserved DRY motif, in the activation of HTR1A. Thus, our
      refined yeast biosensor strain, which incorporates a ZsGreen reporter and an
      engineered Galpha receptor, is expected to serve as a simple and practical
      sensing tool for evaluating the ligand candidates and defining residues important
      to the function of human GPCRs. Biotechnol.

PMID- 25850569
TI  - The metabolic control of schistosome egg production.
AB  - Schistosomiasis is a neglected tropical disease caused by infection with
      trematode parasites of the genus Schistosoma. Despite ongoing treatment
      programmes, the prevalence of schistosomiasis has failed to decline and the
      disease remains a cause of severe morbidity in millions of people. Understanding
      the biology of egg production by schistosomes is critical since eggs allow
      transmission of the infection, and when trapped in host tissues induce the immune
      responses that are responsible for the pathologic changes that underlie disease
      development. Unusually among trematodes, adult schistosomes exhibit sexual
      dimorphism and display a fascinating codependency in that the female is dependent
      on the male to grow and sexually mature. Thus, virgin females are developmentally
      stunted compared with females from mixed-sex infections and are unable to lay
      eggs. Moreover, fecund female schistosomes rapidly lose the ability to produce
      eggs when placed in tissue culture. Here we discuss the metabolic regulation of
      egg production in schistosomes, and in particular the critical role played by
      fatty acid oxidation in this process. 

PMID- 25850572
TI  - Outcomes and cost minimisation associated with outpatient parenteral
      antimicrobial therapy (OPAT) for foot infections in people with diabetes.
AB  - OBJECTIVE: To determine clinical outcomes in patients with diabetic foot
      infections receiving outpatient parenteral antimicrobial therapy (OPAT), to
      evaluate cost savings from the use of OPAT and to analyse demographic, clinical
      and laboratory data that may predict OPAT failure. RESEARCH DESIGN AND
      METHODOLOGY: A retrospective cohort analysis was conducted between 1 January 2007
      and 7 July 2012 at a tertiary referral hospital in metropolitan Sydney. Patients
      with diabetic foot infection were identified from the outpatient parenteral
      antimicrobial therapy database. Demographic, clinical, laboratory and operative
      report data were obtained from patient charts and electronic medical records.
      Potential cost savings were calculated on the estimated cost of expenditure
      versus the expected savings. Linear regression was used to explore outcomes
      associated with outpatient parenteral antimicrobial therapy failure. RESULTS:
      Fifty-nine patients were identified over the 5-year study period. The outpatient
      parenteral antimicrobial therapy success rate for diabetic foot infections was
      88%. Following the resolution of the primary episode of infection, new infective
      episodes within the study period were high (n = 26, 44%). Regression analysis of
      variables for OPAT failure failed to indicate any factors reaching statistical
      significance. A total of 1569 days were saved by using outpatient parenteral
      antimicrobial therapy for an estimated total cost saving of $983,645 or $16,672
      per patient. CONCLUSION: Outpatient intravenous therapy for diabetic foot
      infections is an effective mode of treatment that can contribute to significant
      healthcare savings. High re-infection rates associated with diabetes foot
      ulceration in this population underline the need for close monitoring and
      management of these patients in multidisciplinary high-risk foot setting.

PMID- 25850573
TI  - Cerebral white matter fractional anisotropy and tract volume as measured by MR
      imaging are associated with impaired cognitive and motor function in pediatric
      posterior fossa tumor survivors.
AB  - BACKGROUND: Disease and therapy cause brain damage and subsequent functional loss
      in pediatric patients with posterior fossa tumors. Treatment-related toxicity
      factors are resection in patients with pilocytic astrocytoma (PA) and,
      additionally, cranio-spinal irradiation together with chemotherapy in patients
      with medulloblastoma (MB). We tested whether damage to white matter (WM) as
      revealed by diffusion tensor MR imaging (DTI) correlated with specific cognitive
      and motor impairments in survivors of pediatric posterior fossa tumors.
      PROCEDURES: Eighteen MB (mean age +/- SD, 15.2 +/- 4.9 y) and 14 PA (12.6 +/- 5.0
      y) survivors were investigated with DTI on a 3-Tesla-MR system. We identified
      fractional anisotropy (FA) of WM, the volume ratio of WM to gray matter and
      cerebrospinal fluid (WM/GM + CSF), and volume of specific frontocerebellar
      tracts. Ataxia was assessed using the International Cooperative Ataxia Rating
      Scale (ICARS), while the Wechsler Intelligence Scale for Children determined full
      scale intelligence quotients (FSIQ). Amsterdam Neuropsychological Tasks (ANT) was
      used to assess processing speed. Handwriting automation was analyzed using a
      digitizing graphic tablet. RESULTS: The WM/GM + CSF ratio correlated
      significantly with cognitive measures (IQ, P = 0.002; ANT baseline speed, P =
      0.04; ANT shifting attention, P = 0.004). FA of skeletonized tracts correlated
      significantly with FSIQ (P = 0.008), ANT baseline speed (P = 0.028) and ANT
      shifting attention (P = 0.045). Moreover, frontocerebellar tract volumes
      correlated with both the FSIQ (P = 0.011) and ICARS (P = 0.007). CONCLUSION: DTI
      provides a method for quantification of WM damage by tumor and by therapy
      associated effects in survivors of pediatric posterior fossa tumors. DTI-derived
      WM integrity may be a representative marker for cognitive and motor
      deterioration.

PMID- 25850574
TI  - Effects of early vitamin D deficiency rickets on bone and dental health, growth
      and immunity.
AB  - Vitamin D deficiency is associated with adverse health outcomes, including
      impaired bone growth, gingival inflammation and increased risk for autoimmune
      disease, but the relationship between vitamin D deficiency rickets in childhood
      and long-term health has not been studied. In this study, we assessed the effect
      of early vitamin D deficiency on growth, bone density, dental health and immune
      function in later childhood to determine if children previously diagnosed with
      rickets were at greater risk of adverse health outcomes compared with healthy
      children. We measured serum 25-hydroxyvitamin D, calcium, parathyroid hormone,
      bone mineral density, anthropometric measures, dietary habits, dental health,
      general health history, and markers of inflammation in 14 previously diagnosed
      rickets case children at Children's Hospital Oakland Research Center. We compared
      the findings in the rickets cases with 11 healthy children selected from the
      population of CHO staff families. Fourteen mothers of the rickets cases, five
      siblings of the rickets cases, and seven mothers of healthy children also
      participated. Children diagnosed with vitamin D deficiency rickets had a greater
      risk of fracture, greater prevalence of asthma, and more dental enamel defects
      compared with healthy children. Given the widespread actions of vitamin D, it is
      likely that early-life vitamin D deficiency may increase the risk of disease
      later in childhood. Further assessment of the long-term health effects of early
      deficiency is necessary to make appropriate dietary recommendations for infants
      at risk of deficiency.

PMID- 25850575
TI  - CD14++ CD16+ HLA-DR+ Monocytes in Peripheral Blood are Quantitatively Correlated
      with the Severity of Pre-eclampsia.
AB  - PROBLEM: We aim to investigate the proportion and absolute counts of peripheral
      blood monocyte subsets in women with normal pregnancy (NP) and pre-eclampsia
      (PE), and their correlation with the clinical manifestation and severity of PE.
      METHOD OF STUDY: Peripheral blood was obtained from women with NP (n = 30), mild
      PE (MPE, n = 15) and severe PE (SPE, n = 30). The proportion and absolute counts
      of CD16(+) monocytes and the subsets including intermediate (CD14(++) CD16(+) HLA
      DR(+) ) and non-classical (CD14(+) CD16(++) HLA-DR(+) ) monocytes were determined
      by flow cytometric analysis. RESULTS: Women with MPE and SPE had significantly
      increased absolute count of CD14(++) CD16(+) HLA-DR(+) monocyte subsets (P < 0.01
      each) as compared to NP women. In addition, there were significant differences in
      the absolute count of CD14(++) CD16(+) HLA-DR(+) monocyte subsets between MPE and
      SPE groups (P < 0.05). The proportion of CD14(++) CD16(+) HLA-DR(+) monocyte
      subsets was significantly increased in SPE compared to MPE and NP (P < 0.01
      each). The absolute count (r = 0.332, P < 0.05) and proportion (r = 0.447, P <
      0.01) of CD14(++) CD16(+) HLA-DR(+) monocytes were positively correlated with the
      severity of PE. Multivariate logistic regression analysis further revealed that
      the absolute count of CD14(++) CD16(+) HLA-DR(+) monocytes was a potential marker
      for PE (P < 0.01). CONCLUSION: A preferential increase in peripheral blood
      CD14(++) CD16(+) HLA-DR(+) monocytes is quantitatively correlated with clinical
      manifestation of PE.

PMID- 25850578
TI  - Negative differential resistance in monolayer WTe2 tunneling transistors.
AB  - We report theoretical investigations of quantum transport in monolayer transition
      metal dichalcogenide (TMDC) tunneling field effect transistors (TFETs). Due to
      the specific electronic structure of TMDC WTe(2), a transmission valley is found
      in the conduction band (CB). For a proper choice of the doping, gate and supply
      voltages the WTe(2) TFET can produce a giant negative differential resistance
      (NDR) with a peak to valley ratio as large as 10(3). The mechanism of NDR is
      identified to be due to a transport-mode bottleneck, i.e., the band to band
      tunneling from the valence band of the source is partially blocked by a
      transmission valley of the CB of the drain. More generally, our calculations show
      that electronic structures of at least six TMDC materials possess the
      transmission valley.

PMID- 25850576
TI  - Simultaneous fingerprint and high-wavenumber fiber-optic Raman spectroscopy
      enhances real-time in vivo diagnosis of adenomatous polyps during colonoscopy.
AB  - Colorectal cancer can be prevented if detected early (e.g., precancerous polyps
      adenoma). Endoscopic differential diagnosis of hyperplastic polyps (that have
      little or no risk of malignant transformation) and adenomas (that have prominent
      malignant latency) remains an unambiguous clinical challenge. Raman spectroscopy
      is an optical vibrational technique capable of probing biomolecular changes of
      tissue associated with neoplastic transformation. This work aims to apply a fiber
      optic simultaneous fingerprint (FP) and high wavenumber (HW) Raman spectroscopy
      technique for real-time in vivo assessment of adenomatous polyps during clinical
      colonoscopy. We have developed a fiber-optic Raman endoscopic technique capable
      of simultaneously acquiring both the FP (i.e., 800-1800 cm(-1)) and HW (i.e.,
      2800-3600 cm(-1)) Raman spectra from colorectal tissue subsurface (<200 um) for
      real-time assessment of colorectal carcinogenesis. In vivo FP/HW Raman spectra
      were acquired from 50 patients with 17 colorectal polyps during clinical
      colonoscopy. Prominent Raman spectral differences (p < 0.001) were found between
      hyperplastic (n = 118 spectra), adenoma (n = 184 spectra) that could be
      attributed to changes in inter- and intra-cellular proteins, lipids, DNA and
      water structures and conformations. Simultaneous FP/HW Raman endoscopy provides a
      diagnostic sensitivity of 90.9% and specificity of 83.3% for differentiating
      adenoma from hyperplastic polyps, which is superior to either the FP or HW Raman
      technique alone. This study shows that simultaneous FP/HW Raman spectroscopy
      technique has the potential to be a clinically powerful tool for improving early
      diagnosis of adenomatous polyps in vivo during colonoscopic examination.

PMID- 25850579
TI  - Targeting the immune system in head and neck cancer.

PMID- 25850580
TI  - Update in germ cell tumours.
AB  - PURPOSE OF REVIEW: The purpose of this study is to update the reader on advances
      in postpubertal male germ cell tumours (GCTs) over the last 18 months. RECENT
      FINDINGS: Single nucleotide polymorphisms, including in four sex-determination
      genes, have been identified as additional genetic susceptibility loci to
      testicular GCT development. New insights into cisplatin resistance implicate the
      PDGFR-PIK3CA-AKT and RAS pathways. Circulating tumour cells and circulating
      microRNAs are potential new biomarkers. In clinical stage I (CS-I) GCT, two large
      studies have confirmed the excellent outcomes achieved with surveillance, which
      is now the management option of choice for CS I-A nonseminoma and all CS-I
      seminomas; CS I-B nonseminoma remains controversial. First-line trials of dose
      dense multidrug regimens reported promising results but have not yet supplanted
      BEPx4. Survivorship issues, including secondary malignancies from chemotherapy,
      remain important in this disease and are a continuing focus of ongoing research.
      SUMMARY: Important research questions remain across all aspects of GCT. The next
      decade is likely to produce many new and exciting discoveries that will benefit
      GCT patients.

PMID- 25850582
TI  - Gender differences in the association between lifestyle behaviors and diabetes
      distress in a community sample of adults with type 2 diabetes.
AB  - BACKGROUND: The present study examined the association between moderate and
      severe diabetes distress (DD) and lifestyle behaviors (physical activity,
      smoking, alcohol consumption) in a community sample of adults with type 2
      diabetes mellitus (T2DM). METHODS: A total of 1971 adults with T2DM were
      recruited using mixed methods sampling. Participants were considered eligible if
      they had a doctor diagnosis of T2DM (<=10 years), were insulin naive, aged 40-75
      years, and were from Quebec, Canada. Participants provided information on DD,
      lifestyle behaviors, sociodemographic, and diabetes-related factors. Multinomial
      logistic regressions examined the association between moderate and severe DD and
      each lifestyle behavior, according to gender. Effect estimates can be interpreted
      as probability ratios (PR). RESULTS: In females, physical inactivity was
      associated with an increased likelihood of moderate distress (PR 2.2; 95%
      confidence interval [CI] 1.49-3.24) and severe distress (PR 1.80; 95% CI 1.00
      3.24). In males, only severe distress was associated with physical inactivity (PR
      1.92; 95% CI 1.00-3.66). Current smoking was associated with a greater
      probability of severe distress in males (PR 3.0; 95% CI 1.54-5.84) and females
      (PR 1.32; 95% CI 0.67-2.60); however this effect was stronger in males. No
      association was found between alcohol consumption and DD in females. In males,
      frequent alcohol consumption was associated with a reduced probability of
      moderate (PR 0.56; 95% CI 0.34-0.91) and severe distress (PR 0.47; 95% CI 0.21
      1.06). CONCLUSIONS: The findings of this study suggest important gender
      differences in the association between DD and lifestyle behaviors.

PMID- 25850583
TI  - ART for head and neck patients: On the difference between VMAT and IMPT.
AB  - Anatomical changes in the head-and-neck (H&N) region during the course of
      treatment can cause deteriorated dose distributions. Different replanning
      strategies were investigated for volumetric modulated arc therapy (VMAT) and
      intensity-modulated proton therapy (IMPT). MATERIAL AND METHODS: For six H&N
      patients two repeated computed tomography (CT) and magnetic resonance (MR)
      (CT1/MR1 at week 2 and CT2/MR2 at week 4) scans were acquired additionally to the
      initial planning CT/MR. Organs-at-risk (OARs) and three targets (CTV70Gy,
      CTV63Gy, CTV56Gy) were delineated on MRs and transferred to respective CT data
      set. Simultaneously integrated boost plans were created using VMAT (two arcs) and
      IMPT (four beams). To assess the need of replanning the initial VMAT and IMPT
      plans were recalculated on repeated CTs. Furthermore, VMAT and IMPT plans were
      replanned on the repeated CTs. A Demon algorithm was used for deformable
      registration of the repeated CTs with the initial CT and utilized for dose
      accumulation. Total dose estimations were performed to compare ART versus
      standard treatment strategies. RESULTS: Dosimetric evaluation of recalculated
      plans on CT1 and CT2 showed increasing OAR doses for both, VMAT and IMPT. The
      target coverage of recalculated VMAT plans was considered acceptable in three
      cases, while for all IMPT plans it dropped. Adaptation of the treatment reduced
      D2% for brainstem by 6.7 Gy for VMAT and by 8 Gy for IMPT, for particular
      patients. These D2% reductions were reaching 9 Gy and 14 Gy for the spinal cord.
      ART improved target dose homogeneity, especially for protons, i.e. D2% decreased
      by up to 8 Gy while D98% increased by 1.2 Gy. CONCLUSION: ART showed benefits for
      both modalities. However, as IMPT is more conformal, the magnitude of dosimetric
      changes was more pronounced compared to VMAT. Large anatomic variations had a
      severe impact on treatment plan quality for both VMAT and IMPT. ART is justified
      in those cases irrespective of treatment modalities.

PMID- 25850584
TI  - A molecular characterization of the agonist binding site of a nematode cys-loop
      GABA receptor.
AB  - BACKGROUND AND PURPOSE: Cys-loop GABA receptors represent important targets for
      human chemotherapeutics and insecticides and are potential targets for novel
      anthelmintics (nematicides). However, compared with insect and mammalian
      receptors, little is known regarding the pharmacological characteristics of
      nematode Cys-loop GABA receptors. Here we have investigated the agonist binding
      site of the Cys-loop GABA receptor UNC-49 (Hco-UNC-49) from the parasitic
      nematode Haemonchus contortus. EXPERIMENTAL APPROACH: We used two-electrode
      voltage-clamp electrophysiology to measure channel activation by classical GABA
      receptor agonists on Hco-UNC-49 expressed in Xenopus laevis oocytes, along with
      site-directed mutagenesis and in silico homology modelling. KEY RESULTS: The
      sulphonated molecules P4S and taurine had no effect on Hco-UNC-49. Other
      classical Cys-loop GABAA receptor agonists tested on the Hco-UNC-49B/C
      heteromeric channel had a rank order efficacy of GABA > trans-4-aminocrotonic
      acid > isoguvacine > imidazole-4-acetic acid (IMA) > (R)-(-)-4-amino-3
      hydroxybutyric acid [R(-)-GABOB] > (S)-(+)-4-amino-3-hydroxybutyric acid [S(+)
      GABOB] > guanidinoacetic acid > isonipecotic acid > 5-aminovaleric acid (DAVA)
      (partial agonist) > beta-alanine (partial agonist). In silico ligand docking
      revealed some variation in binding between agonists. Mutagenesis of a key serine
      residue in binding loop C to threonine had minimal effects on GABA and IMA but
      significantly increased the maximal response to DAVA and decreased twofold the
      EC50 for R(-)- and S(+)-GABOB. CONCLUSIONS AND IMPLICATIONS: The pharmacological
      profile of Hco-UNC-49 differed from that of vertebrate Cys-loop GABA receptors
      and insect resistance to dieldrin receptors, suggesting differences in the
      agonist binding pocket. These findings could be exploited to develop new drugs
      that specifically target GABA receptors of parasitic nematodes.

PMID- 25850585
TI  - Teaching pediatric and adolescent gynecology.

PMID- 25850586
TI  - Applying the one minute preceptor model to pediatric and adolescent gynecology
      education.
AB  - There are multiple challenges to teaching in the clinical setting. The One Minute
      Preceptor is a learner-centered model for effective and efficient teaching in a
      clinical setting that can help to overcome these challenges. It consists of 5
      microskills: get a commitment; probe for supporting evidence; teach general
      rules; reinforce what was right; correct mistakes. This article illustrates with
      case vignettes the use of these microskills for the busy Pediatric and Adolescent
      Gynecology clinician. 

PMID- 25850587
TI  - Diagnostic characteristics and metabolic risk factors of cases with polycystic
      ovary syndrome during adolescence.
AB  - STUDY OBJECTIVE: Polycystic ovary syndrome (PCOS) is a disorder without definite
      consensus on its diagnosis and management during adolescence. According to
      Amsterdam-2012 consensus, as physiological characteristics of adolescence may
      overlap with PCOS signs, it has been indicated that all Rotterdam criteria should
      be met. In this present study, characteristics of adolescents with different
      phenotypes who were diagnosed with PCOS were evaluated; and presence of
      differences for metabolic risk factors between phenotypes were investigated.
      DESIGN: The study was performed on adolescent females. According to phenotypic
      application models, individuals with all Rotterdam diagnostic criteria
      [hyperandrogenism (HA), polycystic ovarian morphology (PCOM), and chronic
      anovulation (CA) on the ultrasonography] were in Group 1 (n = 26); with HA and CA
      were in Group 2 (n = 10); with HA and PCOM were in Group 3 (n = 7); and with CA
      and PCOM were in Group 4 (n = 10). RESULTS: The most common application complaint
      (87%) among 53 cases enrolled in the study was menstrual irregularities, and 57%
      of cases were not obese. When PCOS was evaluated according to phenotypes, it was
      realized that cases that meet all 3 diagnostic Rotterdam criteria according to
      the current recommendation in adolescents. (Group 1) was the most common
      phenotype. Hyperandrogenism was associated with more metabolic abnormalities.
      CONCLUSION: The close monitoring of adolescents, who have 2 diagnostic criteria
      is advisable among PCOS phenotypes. Potentially Groups 2 and 3 which have
      hyperandrogenism, in particular should warrant closer follow-up although they do
      not meet current diagnostic criteria for adolescents.

PMID- 25850588
TI  - Perspectives on family planning services among adolescents at a Boston community
      health center.
AB  - STUDY OBJECTIVE: The aim of this project was to investigate adolescent
      perspectives on family planning services at a community-health center, with the
      intent to inform health center programs aimed at stemming the adolescent
      pregnancy rate. DESIGN: This project was cross-sectional and employed mixed
      methods, including surveys and interviews, for the purposes of quality
      improvement. SETTING: The project was conducted in the obstetrics and gynecology
      clinic at an urban community health center in Boston. PARTICIPANTS: Twenty
      adolescent females (age 16-20) who used services at the health center.
      INTERVENTION: Participants were individually interviewed to assess perspectives
      on family planning services and to identify major influences on methods of
      pregnancy prevention. MAIN OUTCOME MEASURE: Major themes were categorized into
      contraceptive usage, reproductive health knowledge, adult influence and
      communication, barriers to contraceptive care and expectations of a family
      planning clinic. RESULTS: All participants were sexually active and 80% had
      experienced pregnancy. Reproductive health knowledge was variable and in many
      cases limited. Concern about disapproval was a prominent barrier to going to a
      clinician for contraception or advice and parents were not often involved in the
      initial contraception discussion. Other barriers to use of contraception included
      forgetting to use the methods and fear of side effects. CONCLUSION: We identified
      several potentially modifiable factors, including lack of knowledge, concern for
      provider disapproval and fear of side effects that may limit effective use of
      family planning services by adolescents. Further attention should be paid to
      these factors in designing and improving youth-friendly services in ob-gyn
      clinics.

PMID- 25850589
TI  - Breast disorders in girls and adolescents. Is there a need for a specialized
      service?
AB  - INTRODUCTION: Minor breast concerns in childhood and adolescence are common and
      lead to increased anxiety among young patients and their families, particularly
      due to high correlation with breast cancer. However, most breast services aim at
      managing adults and triaging patients with breast cancer, whereas adolescent
      medicine specialists or pediatricians are usually not appropriately trained to
      identify and treat breast pathology. METHODS: We reviewed hospital records of all
      patients attending a pediatric and adolescent gynecology or breast clinic of a
      tertiary referral hospital, with a breast related symptom, between January 2009
      and December 2011. We collected information regarding age at presentation, age at
      menarche, diagnosis, management and outcome. RESULTS: We identified 81 patients
      of which 11 presented with an abnormal nipple or areolar secretion, 33 had a
      palpable lump, 20 had mastitis, and 16 had unequal breast development. One
      patient presented with virginal breast hypertrophy. Three out of 11 of the
      patients with an abnormal secretion had a cyst identified on ultrasonography. Out
      of the palpable lumps 12 were fibroadenomas, 3 were phyllodes tumors, and 14 were
      cystic in nature. The phyllodes tumors and half of the fibroadenomas were
      removed. The remaining fibroadenomas remain under regular ultrasonographic follow
      up. All cases of mastitis were treated conservatively and resolved with broad
      spectrum antibiotic treatment. CONCLUSION: In our series, no malignancies were
      identified. Although 8 patients required surgical treatment, the majority of
      cases were treated conservatively.

PMID- 25850591
TI  - Body image in adolescent pregnancy.
AB  - STUDY OBJECTIVES: To review the existing literature on body image in adolescent
      pregnancy and explore concepts about the relationship between the two. DESIGN: A
      systematic review. SETTING: Peer-reviewed articles were identified through
      MEDLINE (1946-present) and PsycINFO (1806-November 2013), conducted in any
      setting. PARTICIPANTS: Pregnant and postpartum adolescents ages 13-19 y.
      INTERVENTIONS: None. MAIN OUTCOME MEASURE(S): The outcome measures used in the
      studies reviewed varied: themes from focus groups, diary entry analysis,
      Pregnancy and weight gain attitude scale, Edinburgh postnatal depression scale,
      Parenting stress index, Eating disorder inventory, Tennessee self concept scale.
      RESULTS: The search yielded a total of 149 studies, of which 6 were relevant to
      the specific topic and age group. The very limited research shows a dichotomy in
      body image perception during pregnancy in adolescence; some studies show an
      increase in body image disturbance and dissatisfaction during pregnancy in
      adolescents, and other studies reviewed found that the majority of pregnant
      adolescents had positive body image and positive attitudes towards weight gain. A
      bidirectional link between depression and negative body image in adolescent
      pregnancy is suggested. CONCLUSIONS: The current research exploring the
      relationshp between body image and pregnancy in adolescence is limited, both in
      quality and quantity. Future research is needed to evaluate longitudinal models
      that will better inform about potential risk factors for body dissatisfaction
      during pregnancy in adolescence, including the possible role of depression.

PMID- 25850590
TI  - Evidence to incorporate inclusive reproductive health measures in guidelines for
      childhood and adolescent cancer survivors.
AB  - OBJECTIVE: Female childhood cancer survivors are at an increased risk of
      reproductive health impairment. We compared reproductive health outcomes with the
      recommended standard in a cohort of childhood cancer survivors. STUDY DESIGN AND
      PARTICIPANTS: A retrospective chart review of 222 female childhood cancer
      survivors aged 21 years or younger that presented to a tertiary referral center
      between 1997-2008 was initiated. The main outcome measures were the compliance
      with the American Society of Clinical Oncology guidelines for childhood cancer
      survivor management of reproductive health. In particular, we evaluated menstrual
      cycle regularity, fertility preservation counseling, and endocrine profile, as
      defined by follicle stimulating hormone (FSH) and anti-mullerian hormone (AMH)
      levels as surrogate markers for ovarian reserve. Secondary outcomes were to study
      the contribution of survivor clinics in enforcing these guidelines. RESULTS: Of
      136 patients older than 13 years at their last visit, 58 patients (43%) had FSH
      data available and none had AMH data. Patients were stratified into 3 groups
      according to FSH levels. Forty of 58 patients (69%) have normal ovarian reserve
      (FSH level < 10), 10 of 58 patients (17%) have decreased ovarian reserve (FSH
      levels 10-40), and 8 of 58 patients (14%) have premature menopause, defined as
      FSH > 40. Most patients with amenorrhea have elevated FSH levels indicating
      primary ovarian insufficiency, while 3 patients (2.2%) have low FSH levels
      consistent with hypothalamic amenorrhea. None of the patients were counseled on
      fertility preservation. CONCLUSIONS: Reproductive health follow-up in children
      with cancer, including FSH and AMH measurement when indicated, should be
      established and strictly adhered.

PMID- 25850592
TI  - Labial adhesions and outcomes of office management.
AB  - STUDY OBJECTIVE: To evaluate clinical outcomes of labial adhesions (LA) and to
      examine the association between LA, lichen sclerosus (LS), eczema (ECZ), or
      asthma. DESIGN: Retrospective study. SETTING: Single pediatric and adolescent
      gynecology clinic, Houston, Texas. PARTICIPANTS: 50 girls diagnosed with LA from
      2006-2011. INTERVENTIONS AND MAIN OUTCOME MEASURES: Resolution, recurrence,
      single vs multiple treatments, need for surgery, and conditions such as LS, ECZ,
      and asthma were reviewed. RESULTS: Mean age was 19.6 months (range 0-84 months),
      and 48% were Caucasian. Most patients were symptomatic (62%) and all 50 patients
      chose estrogen treatment. The majority (74%) required multiple treatments, as
      opposed to a single treatment (26%). Patients with multiple treatments were more
      likely to be severely agglutinated (P = .05) and to need manual separation after
      failed topical treatment (P = .08). The prevalence of asthma, LS, and ECZ was
      9.8%, 7.8%, and 3.9% respectively. There was no association between LS, ECZ, or
      asthma, and number of treatments. Both asthma (N = 3; 8%), and LS (N = 2; 5%)
      were present among the severe agglutinated group; however, this difference was
      not statistically significant (P values .59 and .99). No association with ECZ was
      seen in either group. CONCLUSION: Severe agglutination tends to be associated
      with need of multiple treatments and manual separation. A concurrent diagnosis of
      LS, ECZ, or asthma was not associated with number of treatments but there appears
      to be a trend towards severity of LA in patients with asthma and LS.

PMID- 25850593
TI  - The effect of chromium supplementation on polycystic ovary syndrome in
      adolescents.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is a common condition. Treatment
      with chromium has been shown to improve insulin sensitivity in adults with PCOS.
      Treatment of adolescents with PCOS remains a challenge. OBJECTIVE: To investigate
      the effect of chromium supplementation on the various components of polycystic
      ovary syndrome in adolescent girls. PATIENTS AND METHODS: Thirty-five adolescent
      girls with PCOS were enrolled. History of menstrual irregularities was recorded.
      All underwent physical examination for presence of acne, scoring of hirsutism,
      and calculation of body mass index. Pelvic ultrasonography was done and serum
      free testosterone was measured in all subjects. All subjects received 1000 MUg
      chromium picolinate for 6 months followed by re-evaluation. RESULTS: Mean (SD)
      age was 15.5 (1) years (range: 14-17 y). No significant change in BMI standard
      deviation score (SDS) with chromium supplementation was noted (1.9 (0.7) SDS vs 2
      (0.7) SDS, P = .638). The number of patients with oligo/amenorrhea decreased with
      treatment (29/35 (83%) versus 11/35 (31%), P < .001). Significant reduction in
      mean ovarian volume (P < .001), total follicular count (P < .034), and free
      testosterone (P< .002) was observed. No significant improvement in acne or
      hirsutim was noted. CONCLUSION: Supplementation with chromium to adolescents with
      PCOS is a promising treatment option.

PMID- 25850594
TI  - Infertility and the presence of insulin resistance are associated with increased
      oxidative stress in young, non-obese Turkish women with polycystic ovary
      syndrome.
AB  - STUDY OBJECTIVE: To investigate the relationship between both insulin resistance
      and fertility and the oxidant/antioxidant system in young, non-obese patients
      diagnosed with polycystic ovary syndrome (PCOS). DESIGN: Case-control study.
      SETTING: Department of Obstetrics and Gynecology, Ege University, Izmir, Turkey.
      PARTICIPANTS: PCOS patients without insulin resistance (IR-) (n = 33), PCOS
      patients with insulin resistance (IR+) (n = 27), and healthy controls (n = 30).
      Patients with PCOS and regular sexual intercourse were further divided into
      infertile (n = 14) and fertile (n = 15) groups. MAIN OUTCOME MEASURES: The
      malondialdehyde (MDA) and thiol levels as well as the catalase (CAT) and
      superoxide dismutase (SOD) enzyme activities. RESULTS: Both IR+ and IR- PCOS
      patients had higher MDA levels and lower thiol levels when compared to the
      controls (each P < .001). However, only IR- patients had significantly higher SOD
      (3700.81 +/- 410.13 vs 2614.19 +/- 611.80 U/g Hb; P < .001) and CAT (7565.06 +/-
      628.27 vs 6819.61 +/- 539.2 U/g Hb; P < .001) activities when compared to the
      controls. Infertile PCOS patients had significantly higher MDA levels (347.5 +/-
      22.8 vs 278.6 +/- 42.6 nmol/g Hb, P < .001) and lower thiol levels (498.5 +/-
      56.2 vs 568.5 +/- 38.6 MUmol/l, P = .001) when compared to fertile patients.
      CONCLUSIONS: The results of this study demonstrated an imbalance in the oxidative
      antioxidative system of PCOS patients. This imbalance was worse in IR+ and
      infertile PCOS patients.

PMID- 25850595
TI  - Working with the Food and Drug Administration's Center for Devices to Advance
      Regulatory Science and Medical Device Innovation.

PMID- 25850597
TI  - Highly Efficient Ruthenium-Catalyzed N-Formylation of Amines with H2 and CO2.
AB  - A highly efficient catalyst system based on ruthenium-pincer-type complexes has
      been discovered for N-formylation of various amines with CO2 and H2, thus
      affording the corresponding formamides with excellent productivity (turnover
      numbers of up to 1,940,000 in a single batch) and selectivity. Using a simple
      catalyst recycling protocol, the catalyst was reused for 12 runs in N,N
      dimethylformamide production without significant loss of activity, thus
      demonstrating the potential for practical utilization of this cost-effective
      process. A one-pot two-step procedure for hydrogenation of CO2 to methanol via
      the intermediacy of formamide formation has also been developed.

PMID- 25850598
TI  - Long-term Auditory Symptoms in Patients With Sporadic Vestibular Schwannoma: An
      International Cross-Sectional Study.
AB  - BACKGROUND: There are limited data on the long-term auditory symptoms in patients
      with sporadic small- and medium-sized vestibular schwannoma (VS). The initial
      treatment strategy for VS is controversial. OBJECTIVE: To characterize auditory
      symptoms in a large cohort of patients with VS. METHODS: Patients with <=3 cm VS
      who underwent primary microsurgery, gamma knife surgery, or observation between
      1998 and 2008 at 2 independent hospitals were identified. Clinical data were
      extracted from existing VS databases. At a mean time of 7.7 years after initial
      treatment, patients were surveyed via mail with the use of the Hearing Handicap
      Inventory for Adults (HHIA) and the Tinnitus Handicap Inventory. RESULTS: The
      response rate was 79%; a total of 539 respondents were analyzed. Overall, the
      hearing prognosis was poor, because more than 75% of all patients had
      nonserviceable hearing at the last clinical follow-up. Good baseline hearing
      proved to be a strong predictor for maintained serviceable hearing. Treatment
      modality was independently associated with both audiometric outcome and HHIA
      results. Active treatment with microsurgery or gamma knife surgery did not appear
      to be protective, because patients who were observed had the greatest probability
      of durable hearing. Patients in the surgical series had the greatest hearing
      loss. Tinnitus Handicap Inventory results were less predictable. The only
      predictors of tinnitus handicap were age and HHIA score. CONCLUSION: The overall
      prognosis for hearing in sporadic VS is poor regardless of treatment strategy.
      Treatment modality was an independent predictor of hearing status; observation
      was associated with the highest rate of hearing preservation. .

PMID- 25850599
TI  - The effects of anatomic variations on stereotactic laser amygdalohippocampectomy
      and a proposed protocol for trajectory planning.
AB  - BACKGROUND: Stereotactic laser amygdalohippocampectomy (SLAH) is a promising
      minimally invasive alternative for mesial temporal lobe epilepsy. As seizure
      outcome has been associated with the extent of amygdalar and hippocampal
      ablation, it is important to select a safe trajectory optimizing involvement of
      both structures; however, variations in temporal anatomy significantly affect the
      overall complexity of planning. OBJECTIVE: To quantify anatomic variables of SLAH
      and facilitate stereotactic planning by developing a protocol for optimally
      targeting the amygdalohippocampal complex (AHC). METHODS: We performed a
      retrospective analysis of 19 SLAHs. Anatomic measurements from preoperative
      magnetic resonance imaging and laser trajectory measurements from coregistered
      postoperative magnetic resonance imaging were taken in 11 patients. Simple linear
      regression analysis was performed to identify significant predictor variables
      determining ablation extent. Based on these data, a protocol for optimal
      trajectory planning was developed and subsequently implemented in 8 patients.
      RESULTS: The medial angle of the laser trajectory correlated with the medial
      angle of the AHC. The length of amygdalar cannulation was predictive of its
      ablation volume. All trajectories passed through a posteroinferior corridor
      formed by the lateral ventricle superiorly and collateral sulcus inferiorly. Our
      protocol facilitated planning and increased the volume of AHC ablation.
      CONCLUSION: The medial AHC angle dictates the medial trajectory angle and a path
      from the posteroinferior corridor through the hippocampus and the center of the
      amygdala dictates the caudal angle. These observations led to a protocol for long
      axis AHC cannulation that maintains an extraventricular trajectory to minimize
      hemorrhage risk and targets the center of the amygdala to optimize ablation
      volumes.

PMID- 25850600
TI  - The Mechanism of Ligamentum Flavum Hypertrophy: Introducing Angiogenesis as a
      Critical Link That Couples Mechanical Stress and Hypertrophy.
AB  - BACKGROUND: Biochemical alterations associated with mechanical stress have been
      explored as an initiating step in the pathological progression of ligamentum
      flavum hypertrophy (LFH); however, this mechanism remains poorly understood.
      Recently, the inflammation induced after mechanical stress and the subsequent
      response of ligamentum flavum (LF) cells have been implicated in LFH pathology.
      OBJECTIVE: To investigate the hypothesis that angiogenesis may be a critical link
      between hypertrophy and a series of stimulating events, including mechanical
      stress. METHODS: LF from 20 lumbar spinal canal stenosis (LSCS) patients and 16
      non-LSCS patients (control group) were collected during surgery. Patient
      demographic and radiographic data were obtained. The levels of angiogenic factors
      (vascular endothelial growth factor [VEGF], angiopoietin-1, vascular cell
      adhesion molecule, and basic fibroblast growth factor) in the LF were
      investigated by using an enzyme-linked immunosorbent assay. Angiogenesis was also
      quantified by immunohistochemical detection of CD34-positive capillaries. The
      correlations among clinical factors, including radiographic factors, angiogenic
      factors, and angiogenesis, were statistically analyzed. RESULTS: The LSCS group
      was older and exhibited a longer symptom duration, wider segmental motion, and
      thicker LF than the control group. The LSCS group showed significantly higher
      tissue concentrations of VEGF (P < .001) that positively correlated with LF
      thickness (r = 0.557, P < .001) and segmental motion (r = 0.586, P < .001). The
      LSCS group showed significantly more CD34-positive capillaries than the control
      group (P = .004). CONCLUSION: The LSCS group showed greater segmental motion,
      higher VEGF concentrations, and more CD34-positive capillaries than the control
      group. These data indicate that VEGF-mediated angiogenesis following mechanical
      stress may be a critical step within the series of pathological events in LFH.

PMID- 25850601
TI  - Outcomes in Reoperated Low-Grade Gliomas.
AB  - BACKGROUND: Low-grade gliomas (LGGs) comprise a diverse set of intrinsic brain
      tumors that correlate strongly with survival. Data on the effect of reoperation
      are sparse. OBJECTIVE: To evaluate the effect of reoperation on patients with
      LGG. METHODS: Fifty-two consecutive patients with reoperated LGGs treated at the
      University of Washington between 1986 and 2004 were identified and evaluated in a
      retrospective analysis. RESULTS: The average overall survival (OS) for this
      cohort was 12.95 +/- 0.96 years. The overall 10-year survival rate was 57%. The
      absence of any residual tumor at either the first or second operation was
      associated with significantly increased OS. Negative prognostic variables for OS
      included the use of upfront radiation and pathology at recurrence. The average
      overall progression-free survival to the first recurrence (PFS1) was 6.23 +/-
      0.51 years. Positive prognostic factors for improved PFS1 included the use of
      upfront radiation therapy. Variables not associated with differences in PFS1
      included the use of upfront chemotherapy, enhancement, pathology, extent of
      resection, the presence of residual tumor, and Karnofsky Performance Scale score
      <80. The average overall progression-free survival to the second recurrence was
      2.73 +/- 0.39 years. Pathology at recurrence was associated with significant
      differences in progression-free survival to the second recurrence, as was extent
      of resection at time of first recurrence, and Karnofsky Performance Scale score
      <80. CONCLUSION: This is among the largest studies to assess variables associated
      with outcome in patients with reoperated LGG. Reresection appears to provide
      significant benefit, and extent of resection remains the strongest predictor of
      OS.

PMID- 25850602
TI  - An Unusual Case of Constitutional Mismatch Repair Deficiency Syndrome With
      Anaplastic Ganglioglioma, Colonic Adenocarcinoma, Osteosarcoma, Acute Myeloid
      Leukemia, and Signs of Neurofibromatosis Type 1: Case Report.
AB  - BACKGROUND AND IMPORTANCE: Constitutional mismatch repair deficiency (CMMRD)
      syndrome is a disorder with recessive inheritance caused by biallelic mismatch
      repair gene mutations, in which mismatch repair defects are inherited from both
      parents. This syndrome is associated with multiple cancers occurring in
      childhood. The most common tumors observed with CMMRD include brain tumors,
      digestive tract tumors, and hematological malignancies. The aim of this study was
      to report new phenotypic expressions of CMMRD syndrome and add new insight to the
      existing knowledge about this disease. A review of the literature was conducted
      and recommendation for surveillance and follow-up in patients with CMMRD are
      proposed. CLINICAL PRESENTATION: We report for the first time in the literature,
      the case of a 22-year-old female patient who was diagnosed with CMMRD syndrome,
      with the development of 2 unusual tumors: an anaplastic ganglioglioma and an
      osteosarcoma. She presented initially with an anaplastic ganglioglioma and later
      developed several malignancies including colonic adenocarcinoma, osteosarcoma,
      and acute myeloid leukemia. The patient had an atypical course of her disease
      with development of the initial malignancy at an older age and a remarkably long
      survival period despite developing aggressive tumors. CONCLUSION: Many aspects of
      this disease are still unknown. We identified a case of CMMRD in a patient
      presenting with an anaplastic ganglioglioma, who underwent successful surgical
      resection, chemotherapy, and radiotherapy and has had one of the longest survival
      periods known with this disease. This case broadens the tumor spectrum observed
      with CMMRD syndrome with anaplastic ganglioglioma and osteosarcoma as new
      phenotypic expressions of this genetic defect.

PMID- 25850603
TI  - Validation of a System to Predict Recanalization After Endovascular Treatment of
      Intracranial Aneurysms.
AB  - BACKGROUND: With increasing use of endovascular techniques in the treatment of
      ruptured and unruptured aneurysms, the issue of obliteration efficacy has become
      increasingly important. We have previously reported the Aneurysm Recanalization
      Stratification Scale, which uses accessible predictors including aneurysm
      specific factors (size, rupture, and intraluminal thrombosis) and treatment
      related features (treatment modality and immediate angiographic result) to
      predict retreatment risk after endovascular therapy. OBJECTIVE: To assess the
      external validity of the Aneurysm Recanalization Stratification Scale. METHODS:
      External validity was assessed in independent cohorts from 4 centers in the
      United States and Canada where endovascular and open neurovascular procedures are
      performed, and in a multicenter cohort of 1543 patients. Probability of
      retreatment stratified by risk score was derived for each center and the combined
      multicenter cohort. RESULTS: Despite moderate variability in retreatment rate
      among centers (29.5%, 9.9%, 9.6%, 26.3%, 19.7%, and 18.3%), the Aneurysm
      Recanalization Stratification Scale demonstrated good predictive value with C
      statistics of 0.799, 0.943, 0.780, 0.695, 0.755, and 0.719 for each center and
      the combined cohort, respectively. Probability of retreatment stratified by risk
      score for the combined cohort is as follows: -2, 4.9%; -1, 5.7%; 0, 5.8%; 1,
      13.1%; 2, 19.2%; 3, 34.9%; 4, 32.7%; 5, 73.2%; 6, 89.5%; and 7, 100.0%.
      CONCLUSION: Surgical decision-making and patient-centered informed consent
      require comprehensive and accessible information on treatment efficacy. The
      Aneurysm Recanalization Stratification Scale is a valid prognostic index. This is
      the first comprehensive model that has been developed to quantitatively predict
      retreatment risk following endovascular therapy.

PMID- 25850604
TI  - Exploring the relationship between client perspectives, clinical expertise and
      research evidence.
AB  - PURPOSE: This paper examines the relationship between components of evidence
      based practice (clinical expertise, patient perspective and research evidence).
      METHOD: Findings are examined from two research programs: the Better
      Communication Research Program and Child Talk, including exploratory studies of
      the views of parents and children regarding speech-language pathology and studies
      of current practice by SLPs in England. Systematic reviews of the research
      literature were also undertaken. The paper analyses relationships between
      outcomes valued by children and parents and those reported in the literature and
      in practice, parents' perspectives regarding intervention in comparison with
      clinicians' reports of practice and the extent to which research evidence
      underpins current practice is examined. RESULT: Parents and children value
      functional outcomes and positive experiences; these are not routinely measured in
      research or practice. Therapy is perceived positively by most parents; however,
      some are ambivalent and less clear about the rationale. Commonly used
      interventions are supported by evidence, but there are gaps regarding some
      critical therapy components. CONCLUSION: The paper discusses four challenges to
      evidence-based practice: the consistency and clarity of descriptions of
      interventions; consensus based models of practice; understanding of the
      mechanisms of change; and, finally, the operationalization of client preferences
      within an evidence-based practice framework.

PMID- 25850605
TI  - Implementation and Operational Research: Integration of Family Planning Services
      in a Peer-Managed HIV Care Clinic Serving Most-at-Risk Populations in Phnom Penh,
      Cambodia.
AB  - OBJECTIVE: To assess contraceptive uptake and method choice among women living
      with HIV (WLHIV) attending an HIV care clinic serving most-at-risk women in Phnom
      Penh, Cambodia, before and after the implementation of family planning (FP)
      services. METHODS: Semistructured questionnaires were administered to clients
      before (July, 2011) and after (July, 2012) FP service implementation with
      provision of contraceptive methods (pills, injectables, implants, and
      intrauterine device [IUD]). RESULTS: Among 250 and 249 clients interviewed before
      and after implementation respectively, 24.5% of women reported selling sex for
      money during the last 6 months before and 35.3% after implementation. Awareness
      about contraceptive methods significantly increased among clients
      postimplementation. Among sexually active women, male condom remained the
      contraceptive method of choice with an overall condom use during the last 6
      months at 91% postimplementation vs. 95.6% preimplementation (P = 0.11). Although
      the use of noncondom FP methods increased but not significantly (16.4% after vs.
      12.6% before implementation, P = 0.8), the use of dual method (condom plus
      another method) remained low and did not significantly increase after
      implementation (14.8% after vs. 11.0% before, P = 0.28). CONCLUSIONS: Our results
      show that FP practices of WLHIV attending an HIV care clinic for most-at-risk
      populations did not significantly change after integration on-site provision of a
      wide range of FP methods. Innovative strategies and further research are needed
      to better understand how to promote the use of noncondom FP methods and prevent
      unwanted pregnancies and abortions among most-at-risk women and WLHIV.

PMID- 25850608
TI  - Differences in the treatment and evolution of acute coronary syndromes according
      to gender: what are the causes?
AB  - AIMS AND OBJECTIVES: The objectives of this study were to analyse the differences
      in the treatment and the evolution of acute coronary syndromes according to the
      gender of the patient and to determine the likely causes of these differences.
      BACKGROUND: Epidemiological studies confirm the differences in the course and
      treatment of acute coronary syndromes according to factors such as gender and
      age. The factors associated with the observed gender-based differences are not
      known. DESIGN AND METHODS: This prospective study was conducted on 596 patients
      treated in the Hospital Emergency Service of the Hospital Complex of Navarra,
      Spain, from 1 January 2012 to April 2013 with acute coronary syndromes. A
      bivariate and logistic analysis has been made by adjusting the age and severity
      of process to know the differences by gender. RESULTS: A total of 71.8% (n = 428)
      were men, and the remaining 28.2% (168) were women. The mean age of the men was
      66.4 +/- 12.7 years, and the mean age of the women was 72.5 +/- 13.9 years. We
      found that antiplatelet drugs (68.4 vs. 22.7%), blockers (70 vs. 25.4%), ACE
      inhibitors (56.2 vs. 15.6%), fibrinolysis (17.2 vs. 4.5%, p = 0.025) and primary
      angioplasty (AP) (38.7 vs. 16.3%, p = 0.008) were less frequently administered to
      women compared with men. We observed an additional delay in the demand for health
      care in women with acute coronary syndromes compared with men. CONCLUSIONS: There
      is an association between treatment differences and gender. The delay in the
      request of health care in women is observed to be the largest correlating factor,
      in addition to voluntary discharge in women affected by acute coronary syndromes.
      RELEVANCE TO CLINICAL PRACTICE: Delays in seeking medical care or voluntary
      discharge are likely factors related to worse outcomes in women. These factors
      should be explored, and the results should be made available to the public,
      particularly to women.

PMID- 25850607
TI  - Comparative Safety and Neuropsychiatric Adverse Events Associated With Efavirenz
      Use in First-Line Antiretroviral Therapy: A Systematic Review and Meta-Analysis
      of Randomized Trials.
AB  - INTRODUCTION: Efavirenz (EFV) is widely used for the treatment of antiretroviral
      naive HIV-positive individuals, but there are concerns about the risk of adverse
      neuropsychiatric events. We systematically reviewed the safety of EFV in first
      line therapy. METHODS: Four databases were searched until October 2014 for
      randomized trials comparing EFV against non-EFV-based regimens for the treatment
      of antiretroviral-naive HIV-positive adults and children. The primary outcome was
      drug discontinuation as a result of any adverse event. Relative risks and
      proportions were pooled using random-effects meta-analysis. RESULTS: Forty-two
      trials were included for review. A lower relative and absolute risk of
      discontinuations due to adverse drug reactions was seen with EFV compared to
      nevirapine. The relative and absolute risk of discontinuation was greater for EFV
      compared with low-dose EFV, rilpivirine, tenofovir, atazanavir, and maraviroc.
      The relative risk of discontinuation was greater for EFV compared with
      dolutegravir and raltegravir, but absolute risks were not significantly
      different. There was no difference in the risk of any severe clinical adverse
      events for any comparison. With the exception of dizziness, fewer than 10% of
      patients exposed to EFV experienced any other specific type of neuropsychiatric
      event. No suicides were reported. CONCLUSIONS: This review found that over 90% of
      patients remained on an EFV-based first-line regimen after an average follow-up
      time of 78 weeks. The relative risk of discontinuations due to adverse events was
      higher for EFV compared with most other first-line options, but absolute
      differences were less than 5% for all comparisons.

PMID- 25850609
TI  - Endocrine pregnancy monitoring in the two-toed sloth (Choloepus didactylus):
      "Pregnant or not pregnant".
AB  - Progesterone (P4), pregnanediol glucuronide (PdG), estradiol-17beta (E2), and
      estrone sulfate (E1S) were measured in the feces of four female two-toed sloths
      (Choloepus didactylus) for early pregnancy diagnosis. For individual feces
      assignment, the examined female sloths were fed with a turquoise food colorant
      every second day. Fecal samples were collected one to four times per week,
      depending on the defecation rate throughout the pregnancies and the postpartum
      periods. The complete course of pregnancy was subdivided into three 16-week
      intervals (trimester of pregnancy, TP1-3) and a 5-week post-partum period after
      birth. Progesterone and PdG concentrations started to increase above luteal phase
      levels 3 weeks after conception (P = 0.028 and 0.005, respectively). At the
      beginning of TP1, P4 concentrations averaged 345.0 +/- 283.0 ng/g and increased
      approximately 100- to 300-fold to a peak of 7588.0 +/- 6717.0 ng/g over the TP3.
      Progesterone concentrations were considerably lower than PdG concentrations that
      started with 3206.0 +/- 1500.0 ng/g at TP1 and increased up to 12.8556.0 +/-
      53.744.0 ng/g until birth. In contrast, mean concentrations of E2 (8.2 +/- 2.4
      11.7 +/- 4.2 ng/g) and E1S (12.2 +/- 6.7-22.9 +/- 13.0 ng/g) elevated
      insignificantly and were not suitable for pregnancy detection. All hormones
      analyzed decreased rapidly within the first weeks after birth. Progesterone and
      PdG, as well as E2 and E1S, highly significantly correlated (r = 0.602, P < 0.001
      and r = 0.497, P < 0.001, respectively) at TP1. During the TP2, only P4 and PdG
      significantly correlated (TP2: r = 0.661, P < 0.001 and postpartum period: r =
      0.616, P = 0.009). In summary, only P4 metabolite concentrations were suitable to
      determine the status of reproduction in the two-toed sloth. Thereby, PdG was
      ideally suited to diagnose early pregnancy because it was more sensitive and
      detected pregnancy 2 weeks earlier than P4.

PMID- 25850610
TI  - Occurrence of bacteria and polymorphonuclear leukocytes in fetal compartments at
      parturition; relationships with foal and mare health in the peripartum period.
AB  - This study investigated the relationship of the health of the newborn foal and
      (1) number of polymorphonuclear leukocytes (PMNLs) in the amniotic fluid, (2)
      bacteria present in the amniotic fluid and the venous umbilical blood, and (3)
      bacteria present in the uterus of the newly foaled mare. A further aim was to
      investigate relationships between the bacteriologic findings in the amniotic
      fluid, umbilical blood, and uterus postpartum. Samples were taken from 50
      Standardbred trotter foaling mares from a well-managed stud in Sweden.
      Parturition was spontaneous in all cases. Length of pregnancy, parturition and
      postpartum complications, health status of the foal, the time between foaling and
      the expulsion of the placenta, and the number of postfoaling mares becoming
      pregnant after insemination were recorded. Amniotic fluid was collected when the
      amniotic vesicle was clearly visible; it was analyzed for bacteriology and
      occurrence of PMNLs. Umbilical blood was analyzed for the presence of bacteria
      and the concentration of serum amyloid A. The uterus of the mare was swabbed for
      bacteriology 6 to 17 hours postpartum. A blood sample was taken from the foal
      before administering plasma. The foals were divided into two groups: group 1
      required up to 2 hours to rise after birth (<=2 hours; 31 foals) and group 2
      required more than two hours (>2 hours; 19 foals). The length of gestation varied
      between 332 and 356 days; there was no significant difference in gestation length
      between the two foal groups. Partus and postpartum complications occurred in a
      significantly higher proportion of mares giving birth to group 2 foals than group
      1 foals (P = 0.02), although uterine culture postpartum and the subsequent
      pregnancy rate per season were not different between the groups. Compromised
      health status was significantly higher among foals belonging to group 2 than
      group 1 (P = 0.001). Most of the amniotic samples contained 5% or less PMNLs.
      Only three samples contained more than 30% PMNLs; group 2 foals had the highest
      percentage of PMNLs. Bacterial growth was found in both amniotic fluid (57%) and
      umbilical blood (35%) in mares irrespective of whether their foals were healthy
      or compromised. Coagulase-negative staphylococci were the most frequent bacteria.
      There were no differences in bacterial occurrence in amniotic fluid or in
      umbilical blood between the two foal groups.

PMID- 25850606
TI  - Implementation and Operational Research: Effects of CD4 Monitoring Frequency on
      Clinical End Points in Clinically Stable HIV-Infected Patients With Viral
      Suppression.
AB  - BACKGROUND: Current treatment guidelines for HIV infection recommend routine CD4
      lymphocyte (CD4) count monitoring in patients with viral suppression. This may
      have a limited impact on influencing care as clinically meaningful CD4 decline
      rarely occurs during viral suppression. METHODS: In a regional HIV observational
      cohort in the Asia-Pacific region, patients with viral suppression (2 consecutive
      viral loads <400 copies/mL) and a CD4 count >=200 cells per microliter who had
      CD4 testing 6 monthly were analyzed. Main study end points were occurrence of 1
      CD4 count <200 cells per microliter (single CD4 <200) and 2 CD4 counts <200 cells
      per microliter within a 6-month period (confirmed CD4 <200). A comparison of time
      with single and confirmed CD4 <200 with biannual or annual CD4 assessment was
      performed by generating a hypothetical group comprising the same patients with
      annual CD4 testing by removing every second CD4 count. RESULTS: Among 1538
      patients, the rate of single CD4 <200 was 3.45/100 patient-years and of confirmed
      CD4 <200 was 0.77/100 patient-years. During 5 years of viral suppression,
      patients with baseline CD4 200-249 cells per microliter were significantly more
      likely to experience confirmed CD4 <200 compared with patients with higher
      baseline CD4 [hazard ratio, 55.47 (95% confidence interval: 7.36 to 418.20), P <
      0.001 versus baseline CD4 >=500 cells/MUL]. Cumulative probabilities of confirmed
      CD4 <200 was also higher in patients with baseline CD4 200-249 cells per
      microliter compared with patients with higher baseline CD4. There was no
      significant difference in time to confirmed CD4 <200 between biannual and annual
      CD4 measurement (P = 0.336). CONCLUSIONS: Annual CD4 monitoring in virally
      suppressed HIV patients with a baseline CD4 >=250 cells per microliter may be
      sufficient for clinical management.

PMID- 25850611
TI  - Battles and hijacks: noncoding transcription in plants.
AB  - Noncoding RNAs have emerged as major components of the eukaryotic transcriptome.
      Genome-wide analyses revealed the existence of thousands of long noncoding RNAs
      (lncRNAs) in several plant species. Plant lncRNAs are transcribed by the plant
      specific RNA polymerases Pol IV and Pol V, leading to transcriptional gene
      silencing, as well as by Pol II. They are involved in a wide range of regulatory
      mechanisms impacting on gene expression, including chromatin remodeling,
      modulation of alternative splicing, fine-tuning of miRNA activity, and the
      control of mRNA translation or accumulation. Recently, dual noncoding
      transcription by alternative RNA polymerases was implicated in epigenetic and
      chromatin conformation dynamics. This review integrates the current knowledge on
      the regulatory mechanisms acting through plant noncoding transcription.

PMID- 25850612
TI  - My body aches.

PMID- 25850613
TI  - Mitochondria in autoinflammation: cause, mediator or bystander?
AB  - People suffering from autoinflammatory disease (AID) have recurring sterile
      inflammation due to dysregulated inflammasome activation. Although certain genes
      have been associated with several AIDs, the molecular underpinnings of seemingly
      spontaneous inflammation are not well understood. Emerging data now suggest that
      mitochondrial reactive oxygen species (ROS), mitochondrial DNA (mtDNA), and
      autophagy might drive key signaling pathways towards activation of the
      inflammasome. In this review, we discuss recent findings and highlight common
      features between different AIDs and mitochondrial (dys)function. Although it is
      still early to identify clear therapeutic targets, the emerging paradigms in
      inflammation and mitochondrial biology show that mitochondria play an important
      role in AIDs, and understanding this interplay will be key in the development of
      new therapies. 

PMID- 25850614
TI  - Application of science-based restoration planning to a desert river system.
AB  - Persistence of many desert river species is threatened by a suite of impacts
      linked to water infrastructure projects that provide human water security where
      water is scarce. Many desert rivers have undergone regime shifts from spatially
      and temporally dynamic ecosystems to more stable systems dominated by homogenous
      physical habitat. Restoration of desert river systems could aid in biodiversity
      conservation, but poses formidable challenges due to multiple threats and the
      infeasibility of recovery to pre-development conditions. The challenges faced in
      restoring desert rivers can be addressed by incorporating scientific
      recommendations into restoration planning efforts at multiple stages, as
      demonstrated here through an example restoration project. In particular, use of a
      watershed-scale planning process can identify data gaps and irreversible
      constraints, which aid in developing achievable restoration goals and objectives.
      Site-prioritization focuses limited the resources for restoration on areas with
      the greatest potential to improve populations of target organisms. Investment in
      research to understand causes of degradation, coupled with adoption of a guiding
      vision is critical for identifying feasible restoration actions that can enhance
      river processes. Setting monitoring as a project goal, developing hypotheses for
      expected outcomes, and implementing restoration as an experimental design will
      facilitate adaptive management and learning from project implementation.
      Involvement of scientists and managers during all planning stages is critical for
      developing process-based restoration actions and an implementation plan to
      maximize learning. The planning process developed here provides a roadmap for use
      of scientific recommendations in future efforts to recover dynamic processes in
      imperiled riverine ecosystems. 

PMID- 25850615
TI  - Do global indicators of protected area management effectiveness make sense? A
      case study from Siberia.
AB  - Driven by the underperformance of many protected areas (PAs), protected area
      management effectiveness (PAME) evaluations are increasingly being conducted to
      assess PAs in meeting specified objectives. A number of PAME tools have been
      developed, many of which are based on the IUCN-WCPA framework constituting six
      evaluative elements (context, planning, input, process, output, and outcomes). In
      a quest for a more universal tool and using this framework, Leverington et al.
      (Environ Manag 46(5):685-698, 2010) developed a common scale and list of 33
      headline indicators, purported to be representative across a wide range of
      management effectiveness evaluation tools. The usefulness of such composite tools
      and the relative weighting of indicators are still being debated. Here, we
      utilize these headline indicators as a benchmark to assess PAME in 37 PAs of four
      types in Krasnoyarsk Kray, Russia, and compare these with global results.
      Moreover, we review the usefulness of these indicators in the Krasnoyarsk context
      based on the opinions of local PA management teams. Overall, uncorrected
      management scores for studied PAs were slightly better (mean = 5.66 +/- 0.875)
      than the global average, with output and outcome elements being strongest, and
      planning and process scores lower. Score variability is influenced by PA size,
      location, and type. When scores were corrected based on indicator importance, the
      mean score significantly increased to 5.75 +/- 0.858. We emphasize idiosyncrasies
      of Russian PA management, including the relative absence of formal management
      plans and limited efforts toward local community beneficiation, and how such
      contextual differences may confound PAME scores when indicator weights are
      treated equal.

PMID- 25850616
TI  - Multi-layered polymeric nanoparticles for pH-responsive and sequenced release of
      theranostic agents.
AB  - In this study, multi-layered pH-responsive polymeric nanoparticles (NPs) are
      prepared by multiple (up to 4) emulsifications to encapsulate multiple
      hydrophilic and hydrophobic theranostic agents for controlled and sequenced
      release. It is found that the sequence of release of multiple chemotherapeutic
      agents from the NPs significantly affects their efficacy against cancer cells. 

PMID- 25850617
TI  - Constrained Dual Scaling for Detecting Response Styles in Categorical Data.
AB  - Dual scaling (DS) is a multivariate exploratory method equivalent to
      correspondence analysis when analysing contingency tables. However, for the
      analysis of rating data, different proposals appear in the DS and correspondence
      analysis literature. It is shown here that a peculiarity of the DS method can be
      exploited to detect differences in response styles. Response styles occur when
      respondents use rating scales differently for reasons not related to the
      questions, often biasing results. A spline-based constrained version of DS is
      devised which can detect the presence of four prominent types of response styles,
      and is extended to allow for multiple response styles. An alternating nonnegative
      least squares algorithm is devised for estimating the parameters. The new method
      is appraised both by simulation studies and an empirical application. 

PMID- 25850618
TI  - An Exact Method for Partitioning Dichotomous Items Within the Framework of the
      Monotone Homogeneity Model.
AB  - The monotone homogeneity model (MHM-also known as the unidimensional monotone
      latent variable model) is a nonparametric IRT formulation that provides the
      underpinning for partitioning a collection of dichotomous items to form scales.
      Ellis (Psychometrika 79:303-316, 2014, doi: 10.1007/s11336-013-9341-5 ) has
      recently derived inequalities that are implied by the MHM, yet require only the
      bivariate (inter-item) correlations. In this paper, we incorporate these
      inequalities within a mathematical programming formulation for partitioning a set
      of dichotomous scale items. The objective criterion of the partitioning model is
      to produce clusters of maximum cardinality. The formulation is a binary integer
      linear program that can be solved exactly using commercial mathematical
      programming software. However, we have also developed a standalone branch-and
      bound algorithm that produces globally optimal solutions. Simulation results and
      a numerical example are provided to demonstrate the proposed method. 

PMID- 25850620
TI  - Neuroanatomical Diversity of Corpus Callosum and Brain Volume in Autism: Meta
      analysis, Analysis of the Autism Brain Imaging Data Exchange Project, and
      Simulation.
AB  - BACKGROUND: Patients with autism have been often reported to have a smaller
      corpus callosum (CC) than control subjects. METHODS: We conducted a meta-analysis
      of the literature, analyzed the CC in 694 subjects of the Autism Brain Imaging
      Data Exchange project, and performed computer simulations to study the effect of
      different analysis strategies. RESULTS: Our meta-analysis suggested a group
      difference in CC size; however, the studies were heavily underpowered (20% power
      to detect Cohen's d = .3). In contrast, we did not observe significant
      differences in the Autism Brain Imaging Data Exchange cohort, despite having
      achieved 99% power. However, we observed that CC scaled nonlinearly with brain
      volume (BV): large brains had a proportionally smaller CC. Our simulations showed
      that because of this nonlinearity, CC normalization could not control for
      eventual BV differences, but using BV as a covariate in a linear model would. We
      also observed a weaker correlation of IQ and BV in cases compared with control
      subjects. Our simulations showed that matching populations by IQ could then
      induce artifactual BV differences. CONCLUSIONS: The lack of statistical power in
      the previous literature prevents us from establishing the reality of the claims
      of a smaller CC in autism, and our own analyses did not find any. However, the
      nonlinear relationship between CC and BV and the different correlation between BV
      and IQ in cases and control subjects may induce artifactual differences. Overall,
      our results highlight the necessity for open data sharing to provide a more solid
      ground for the discovery of neuroimaging biomarkers within the context of the
      wide human neuroanatomical diversity.

PMID- 25850621
TI  - Nesfatin-1 and the Cardiovascular System: Central and Pheripheral Actions and
      Cardioprotection.
AB  - Recently, the hypothalamic 82-aa peptide Nesfatin-1 received notable attention
      for its anorexigenic and anti-hyperglycemic properties. In mammalian
      hypothalamus, Nesfatin-1 is expressed, together with the precursor Nucleobindin 2
      (NUCB2), in regions controlling water-food intake, body weight, and glucose
      homeostasis. The peptide is also peripherally expressed, as shown in the rat
      heart, in which it is present together with NUCB2. In addition to a central
      modulation of nutrition and energy balance, and of the nervous circuits
      responsible for blood pressure and heart rate control, Nesfatin-1 also acts
      peripherally on several districts, including the cardiovascular (CV) system.
      Accordingly, the peptide is regarded with interest as a multifunctional hormone
      not only linked to alimentary homeostasis. This review aims to analyze the
      literature on Nesfatin-1, with focus on its emerging CV activity. Few available
      studies show that the peptide affects energy metabolism of murine and human
      cardiomyocytes, by eliciting insulin-like effects. On the ex vivo rat heart, it
      directly depresses contractility and relaxation via cGMP, PKG and ERK1/2, and
      limits ischemia/reperfusion (I/R) damage, acting in post-conditioning protection.
      Nesfatin-1 actions are proposed to involve an unknown G-protein coupled receptor.
      However, in the rat heart, functional studies, co-immunoprecipitation and local
      sequence alignment analyses suggest an interaction with the Natriuretic Peptide
      Receptor-type A (NPR-A). These data open up novel perspectives to clarify not
      only the biological significance of the peptide, but also its putative biomedical
      potential in the presence of nutrition-dependent cardiovascular diseases.

PMID- 25850622
TI  - Identification of Lipid Species Linked to the Progression of Non-Alcoholic Fatty
      Liver Disease.
AB  - Non-alcoholic fatty liver disease (NAFLD) is histologically characterized by the
      aberrant accumulation of lipid droplets in the liver, which is positively
      correlated with insulin resistance. Within the spectrum of this disease, patients
      can develop hepatitis and cirrhosis; i.e., non-alcoholic steatohepatitis (NASH).
      The mechanisms responsible for the progression of NAFLD are not fully understood.
      Triacylglycerol (TAG), which is mainly found in lipid droplets, is currently
      considered to act as a buffer against the accumulation of non-TAG toxic lipid
      species. In line with this, recent studies have revealed that insulin resistance
      is driven by the accumulation of phosphatidic acid and diacylglycerol in
      hepatocytes and that cholesterol-overloaded stellate cells are associated with
      fibrosis in the liver. Therefore, it is important to identify the toxic lipid
      species that contribute to NAFLD progression in order to clarify the pathogenesis
      of NASH and find novel targets for its treatment. In this review, we divided
      lipids into five classes; i.e., into fatty acyls, glycerophospholipids,
      glycerolipids, sphingolipids, and sterol lipids, and described their molecular
      structures, distributions, and metabolism under physiological conditions, as well
      as the contributions they make to the progression of NAFLD. 

PMID- 25850619
TI  - Brain rhythms connect impaired inhibition to altered cognition in schizophrenia.
AB  - In recent years, schizophrenia research has focused on inhibitory interneuron
      dysfunction at the level of neurobiology and on cognitive impairments at the
      psychological level. Reviewing both experimental and computational findings, we
      show how the temporal structure of the activity of neuronal populations,
      exemplified by brain rhythms, can begin to bridge these levels of complexity.
      Oscillations in neuronal activity tie the pathophysiology of schizophrenia to
      alterations in local processing and large-scale coordination, and these
      alterations in turn can lead to the cognitive and perceptual disturbances
      observed in schizophrenia. 

PMID- 25850623
TI  - mTOR: A Novel Therapeutic Target for Diseases of Multiple Systems.
AB  - Significant progress in the research of mammalian target of rapamycin (mTOR) in
      recent years, has greatly enhanced our understanding of the role and cellular
      pathways through which mTOR control cellular processes, such as translational
      initiation, actin organization, cell proliferation, and cell survival. mTOR is
      activated by phosphorylation and functions mainly through mTOR complex 1 or mTOR
      complex 2. mTORC1 is activated through tuberous sclerosis complex 1/2 dependent
      and independent mechanisms following the stimulation by growth factors, nutrient,
      amino acids, and other signaling pathways. The activity of mTOR is closely
      associated with cell proliferation and differentiation, apoptosis, and autophagy.
      Activation of mTOR prevents the induction of both apoptosis and autophagy through
      regulating its multiple targets. Given that the activity of mTOR has been
      involved in the pathogenesis of neurodegenerative disorders, cardiovascular
      abnormalities, metabolic diseases, renal transplantation, autoimmune
      abnormalities, and cancer, manipulating mTOR activation may represent as an
      innovative therapeutic strategy for these diseases. Yet, the role of mTOR in the
      body is complicated and therefore, its activity needs to be tightly regulated to
      achieve beneficial outcome in a specific pathological condition. 

PMID- 25850624
TI  - Role of Free Fatty Acid Receptor 2 (FFAR2) in the Regulation of Metabolic
      Homeostasis.
AB  - Besides being an important source of fuel and structural components of biological
      membranes, free fatty acids (FFAs) are known to display a wide variety of roles
      that include modulation of receptor signaling and regulation of gene expression
      among many. FFAs play a significant role in maintaining metabolic homeostasis by
      activating specific G-Protein Coupled Receptors (GPCRs) in pancreatic beta cells,
      immune cells, white adipose tissue, intestine and several other tissues. Free
      Fatty acid receptor 2 (FFAR2) also known as GPR43 belongs to this group of GPCRs
      and has been shown to participate in a number of important biological activities.
      FFAR2 is activated by short-chain fatty acids (SCFAs) such as acetate, propionate
      and butyrate. SCFAs are formed in the distal gut by bacterial fermentation of
      macro-fibrous material that escapes digestion in the upper gastrointestinal tract
      and enters the colon and have been shown to play vital role in the immune
      regulation and metabolic homeostasis. FFAR2 and other free fatty acid receptors
      are considered key components of the body's nutrient sensing mechanism and
      targeting these receptors is assumed to offer novel therapies for the management
      of diabetes and other metabolic disorders. This review aims to summarize the
      current state of our understanding of FFAR2 biology with a particular focus on
      its role in metabolic homeostasis. 

PMID- 25850625
TI  - Bridging the Gap: The Potential Role of Corticosteroid Binding Globulin in
      Cardiac Steroid Facilitation.
AB  - Corticosteroid (glucocorticoids [GCs] and mineralcorticoids [MCs]) interact
      directly with cells of the cardiovascular system. Their signaling affects genomic
      and non-genomic receptors and comprises a multitude of alternative and
      interfering levels of interaction, which influence the physiological response.
      This review describes genomic and non-genomic pathways of steroid facilitation
      and portrays the current body of knowledge regarding corticosteroid-binding
      globulin (CBG). The latter is a carrier protein facilitating corticosteroid
      availability in the circulation and has recently been discovered intrinsically in
      cardiomyocytes. Thought experiments highlight potential areas of clinical
      research and hypotheses are presented for steroid- carrier interaction.
      Furthermore, this review comprises a conclusive overview of disease conditions
      and substances that influence CBG levels and summarizes the potential of CBG as a
      potential future biomarker. 

PMID- 25850626
TI  - Use of extramural ambulatory care curricula in postgraduate medical training.
AB  - INTRODUCTION: Extramural curricula developed for the purpose of sharing with
      other institutions have been designed to improve education on important topics in
      ambulatory care. We sought to assess the usage rates of these curricula among
      paediatric, internal medicine, and combined medicine-paediatrics residency
      programmes in the United States. METHODS: Surveys on aspects of trainee
      continuity clinic were sent to paediatric and medicine-paediatrics programme
      directors in 2012. Surveys contained an item asking respondents about their use
      of extramural ambulatory care curricula. Since no similar recent data were
      available for internal medicine, and to verify the accuracy of the paediatric
      survey data, we queried the editors of four widely used curricula for
      subscription information. Descriptive and inferential statistics were calculated.
      RESULTS: Responses from paediatric programmes indicated that 48 of 111 (43 %)
      were using an extramural curriculum, compared with 39 of 60 (65 %) medicine
      paediatrics programmes (p = 0.007). Editor query revealed a collective
      subscription rate of internal medicine programmes (300 of 402, 75 %), which was
      greater than the subscription rate of paediatric programmes (90 of 201, 45 %) (p
      < 0.001). DISCUSSION: Training programmes in paediatrics, internal medicine, and
      combined medicine-paediatrics utilize extramural curricula to guide education in
      ambulatory care, but internal medicine and medicine-paediatrics programmes employ
      these curricula at greater rates than paediatric programmes.

PMID- 25850627
TI  - The writer's craft.

PMID- 25850629
TI  - Treatment of recurrent anal fistula using an autologous cartilage plug: a pilot
      study.
AB  - BACKGROUND: The aim of the present study was to assess a novel autologous
      cartilage plug technique used to treat anal fistula in ten patients. METHODS: All
      ten patients had undergone at least two prior operations for recurrent fistulas.
      The plugs were prepared using the patients' own cartilage, which was obtained
      from either the nose or the ear, diced into pieces, and wrapped with oxidized
      regenerated cellulose. During the same session, fistula tracts were curetted
      using cytology brushes, and then, the cartilage plug was inserted into the tract.
      Routine postoperative examinations were performed at 2, 4, 8, 12, and 24 weeks
      after surgery. Magnetic resonance imaging was performed before surgery and at 3
      and 6 months postoperatively. Relief of symptoms, radiological healing,
      recurrence, and continence were evaluated. RESULTS: The ten patients included six
      males and four females, with a median age of 39 years (range 25-70 years) and a
      median of three previous fistula operations (range 2-7 operations). Nine patients
      had cryptoglandular abscess, and one patient had Crohn's disease. The majority of
      the patients had transsphincteric fistulas with substantial anal sphincter
      involvement. The cartilage donor site was the nose for one patient and the ear
      for nine patients. The median follow-up time was 24 months (range 10-32 months).
      Of the ten patients, nine had fistula treatment without any short-term
      complications. The fistula failed to heal in one patient. Among the nine patients
      whose operations were initially successful, two late recurrences were observed.
      CONCLUSIONS: The cartilage plug seems to be a promising alternative for anal
      fistula treatment.

PMID- 25850628
TI  - A US Multicenter Study of Safety and Efficacy of Fully Covered Self-Expandable
      Metallic Stents in Benign Extrahepatic Biliary Strictures.
AB  - BACKGROUND: Endoscopic therapy is considered first line for management of benign
      biliary strictures (BBSs). Placement of plastic stents has been effective but
      limited by their short-term patency and need for repeated procedures. Fully
      covered self-expandable metallic stents (FCSEMSs) offer longer-lasting biliary
      drainage without the need for frequent exchanges. AIMS: The aim of this study was
      to assess the efficacy and safety of FCSEMS in patients with BBS. METHODS: A
      retrospective review of all patients who underwent ERCP and FCSEMS placement at
      five tertiary referral US hospitals was performed. Stricture resolution and
      adverse events related to ERCP and/or stenting were recorded. RESULTS: A total of
      123 patients underwent FCSEMS placement for BBS and 112 underwent a subsequent
      follow-up ERCP. The mean age was 62 years (+/-15.6), and 57% were males.
      Stricture resolution occurred in 81% of patients after a mean of 1.2 stenting
      procedures (mean stent dwell time 24.4 +/- 2.3 weeks), with a mean follow-up of
      18.5 months. Stricture recurrence occurred in 5 patients, and 3 patients required
      surgery for treatment of refractory strictures. Stent migration (9.7%) was the
      most common complication, followed by stent occlusion (4.9%), cholangitis (4.1%),
      and pancreatitis (3.3%). There was one case of stent fracture during removal, and
      one stent could not be removed. There was one death due to cholangitis.
      CONCLUSIONS: Majority of BBS can be successfully managed with 1-2 consecutive
      FCSEMS with stent dwell time of 6 months.

PMID- 25850630
TI  - A rare perianal tumor: solitary fibrous tumor.

PMID- 25850632
TI  - A Case Report of Acute Vitamin A Intoxication due to Ocean Perch Liver Ingestion.
AB  - BACKGROUND: Chronic vitamin A intoxication is well known; however, there are few
      reports of acute vitamin A intoxication due to the ingestion of food rich in
      vitamin A, particularly in adults. CASE REPORT: We report a case of a 27-year-old
      man presenting with chief complaints of flushing, headache, nausea, and joint
      pain. He had consumed 800 g of grilled ocean perch liver the day before and had
      experienced numbness shortly after. Although physical examination revealed only
      facial flushing, we suspected acute vitamin A intoxication due to his diet
      history. On day 2 after ingestion, his serum retinol levels were elevated at 1577
      ng/mL, which confirmed vitamin A intoxication. He returned for follow-up on day 4
      after ingestion, by which time his presenting symptoms had improved, but he had
      developed desquamation of his facial skin. WHY SHOULD AN EMERGENCY PHYSICIAN BE
      AWARE OF THIS?: Emergency physicians should consider acute vitamin A intoxication
      in the differential diagnosis of patients with headache, flushing, desquamation,
      nausea, and vomiting of unknown etiology. Complete diet histories and checking
      vitamin A levels are essential for diagnosis. This report highlights the
      diagnostic difficulties associated with vitamin A intoxication and the importance
      of an accurate diet history.

PMID- 25850633
TI  - Safety and efficacy of milk and molasses enemas in the emergency department.
AB  - BACKGROUND: Increased scrutiny is occurring from regulatory agencies about the
      use of nonsterile enema preparations in the emergency department (ED) for
      constipation. This includes the "off-label" use of milk and molasses (M&M)
      enemas, as there are no reported data in the medical literature to determine
      safety and efficacy. OBJECTIVES: To evaluate the success and complication rates
      of administering M&M enemas in the ED. METHODS: This was a structured
      retrospective study at two EDs over 8 years. Primary success was defined as the
      patient having a bowel movement. Secondary measures of success included improved
      pain score by 2 or more points or lowering of a heart rate initially over 100
      beats/min by 20 or more beats/min. Complications included: hemodynamic
      compromise, increased pain, electrolyte disturbances, bacteremia, bowel
      perforation, rectal pain or bleeding, cardiac dysrhythmias, anaphylaxis,
      electrolyte disturbances, dizziness or syncope, or hospital admission for issues
      surrounding enema. RESULTS: There were 2013 enemas given, of which 261 were M&M
      enemas; 214 were given alone. Success rates defined only as bowel evacuation for
      M&M enemas alone were 87.9% (188/214) and, when used after other treatment
      failures, were 82.4% (28/34) successful. Five additional patients improved with
      the secondary measures (90.2% success). There were 8/261 complications (3.1%), of
      which four had an increased heart rate, two had decreased blood pressure, one had
      an increased pain score, and one subsequently developed a fever. CONCLUSION: M&M
      enemas have a low complication rate when used in the ED.

PMID- 25850634
TI  - Seeing eye to eye: becoming the chaplain in the emergency department of a level I
      trauma center.

PMID- 25850635
TI  - The Influence of Tactile Perception on Classification of Bone Tissue at Dental
      Implant Insertion.
AB  - BACKGROUND: Various ways of using the Lekholm and Zarb (L&Z) classification have
      added to the lack of scientific evidence of the effectiveness of this clinical
      method in the evaluation of implant treatment. PURPOSE: The study aims to assess
      subjective jawbone classifications in patients referred for implant treatment,
      using L&Z classification with and without surgeon's hand perception at implant
      insertion. The association between bone type classifications and quantitative
      parameters of primary implant stability was also assessed. MATERIALS AND METHODS:
      One hundred thirty-five implants were inserted using conventional loading
      protocol. Three surgeons classified bone quality at implant sites using two
      methods: one based on periapical and panoramic images (modified L&Z) and one
      based on the same images associated with the surgeon's tactile perception during
      drilling (original L&Z). Peak insertion torque and implant stability quotient
      (ISQ) were recorded. RESULTS: The modified and original L&Z were strongly
      correlated (rho = 0.79; p < .001); Wilcoxon signed-rank test showed no
      significant difference in the distribution of bone type classification between
      pairs using the two methods (p = .538). Spearman correlation tested the
      association between primary stability parameters and bone type classifications (
      0.34 to -0.57 [p < .001]). CONCLUSIONS: Tactile surgical perception has a minor
      influence on rating of subjective bone type for dental implant treatment using
      the L&Z classification.

PMID- 25850636
TI  - Patients with Psychiatric Disorders Can Also Have CLABSIs: A Response to "CLABSI
      or Munchausen's or Both".

PMID- 25850637
TI  - Characteristics and Diagnostic Yield of Pediatric Colonoscopy in Taiwan.
AB  - BACKGROUND: Colonoscopy of the lower gastrointestinal tract has diagnostic and
      therapeutic value. This retrospective study aimed to investigate the indications,
      complications, and diagnostic yield of diagnostic colonoscopy among Taiwanese
      children. METHODS: The application of colonoscopy performed on children aged < 18
      years between 1998 and 2010 in a referral tertiary center in Southern Taiwan was
      reviewed. Data on age, gender, indications, complications, and colonoscopic and
      final diagnoses were collected and analyzed. RESULTS: One hundred and ninety-two
      children with 201 colonoscopies and 27 sigmoidoscopies were enrolled. The rate of
      successful ileocecal approach was 77.5%. The most common indication was lower
      gastrointestinal bleeding (LGIB; 53.5%), followed by chronic abdominal pain
      (20.6%), iron deficiency anemia (IDA; 11.8%), and chronic diarrhea (11.4%). There
      were 144 patients (75%) with a conclusive diagnosis in their first colonoscopy,
      including nonspecific colitis (23.4%), polyp (20.4%), and inflammatory bowel
      disease (8.3%). The diagnostic yields of colonoscopy according to the major
      indications were 77.3% in LGIB, 68.1% in chronic abdominal pain, 66.7% in IDA,
      and 79.2% in chronic diarrhea. Among the patients with LGIB, juvenile polyp
      (26.4%) was the most common etiology. There were no major procedure-related
      complications. CONCLUSION: LGIB is the most common indication for pediatric
      colonoscopy. Pediatric colonoscopy is most effective in diagnosing pediatric LGIB
      and chronic diarrhea.

PMID- 25850638
TI  - CORAL: model for no observed adverse effect level (NOAEL).
AB  - The in vivo repeated dose toxicity (RDT) test is intended to provide information
      on the possible risk caused by repeated exposure to a substance over a limited
      period of time. The measure of the RDT is the no observed adverse effect level
      (NOAEL) that is the dose at which no effects are observed, i.e., this endpoint
      indicates the safety level for a substance. The need to replace in vivo tests, as
      required by some European Regulations (registration, evaluation authorization and
      restriction of chemicals) is leading to the searching for reliable alternative
      methods such as quantitative structure-activity relationships (QSAR). Considering
      the complexity of the RDT endpoint, for which data quality is limited and depends
      anyway on the study design, the development of QSAR for this endpoint is an
      attractive task. Starting from a dataset of 140 organic compounds with NOAEL
      values related to oral short term toxicity in rats, we developed a QSAR model
      based on optimal descriptors calculated with simplified molecular input-line
      entry systems and the graph of atomic orbitals by the Monte Carlo method, using
      CORAL software. Three different splits into the training, calibration, and
      validation sets are studied. The mechanistic interpretation of these models in
      terms of molecular fragment with positive or negative contributions to the
      endpoint is discussed. The probabilistic definition for the domain of
      applicability is suggested. 

PMID- 25850631
TI  - Laparoscopic cholecystectomy: consensus conference-based guidelines.
AB  - INTRODUCTION: Laparoscopic cholecystectomy (LC) is the gold standard technique
      for gallbladder diseases in both acute and elective surgery. Nevertheless,
      reports from national surveys still seem to represent some doubts regarding its
      diffusion. There is neither a wide consensus on its indications nor on its
      possible related morbidity. On the other hand, more than 25 years have passed
      since the introduction of LC, and we have all witnessed the exponential growth of
      knowledge, skill and technology that has followed it. In 1995, the EAES published
      its consensus statement on laparoscopic cholecystectomy in which seven main
      questions were answered, according to the available evidence. During the
      following 20 years, there have been several additional guidelines on LC, mainly
      focused on some particular aspect, such as emergency or concomitant biliary tract
      surgery. METHODS: In 2012, several Italian surgical societies decided to revisit
      the clinical recommendations for the role of laparoscopy in the treatment of
      gallbladder diseases in adults, to update and supplement the existing guidelines
      with recommendations that reflect what is known and what constitutes good
      practice concerning LC.

PMID- 25850640
TI  - Presurgical MR Imaging in Epilepsy.
AB  - Primary goal of magnetic resonance imaging in epilepsy patients is to detect
      epileptogenic lesions with small lesions best detectable on a 3D FLAIR SPACE
      sequence with 1 mm(3) voxels. Morphometric analysis of 3D T1-weighted data sets
      helps to find subtle lesions and may reveal the true extent of a lesion. In
      further presurgical work-up, language lateralization and spatial relationship of
      epileptogenic lesions to eloquent cortex and white matter tracts must be
      evaluated. With clear left lateralization language, fMRI is sufficient; in
      atypical lateralizations, Wada test and electrical stimulation mapping may be
      added. Primary motor cortex and corticospinal tract on one and visual cortex and
      optic radiation on the other side are displayed with fMRI and diffusion tensor
      tractography. For the corticospinal tract a "global" tracking algorithm, for the
      optic radiation including Meyer' loop, which may be damaged in anterior temporal
      lobe resections, a probabilistic algorithm is best suited.

PMID- 25850641
TI  - [With increasing weight there is also increasing risk].

PMID- 25850639
TI  - In vivo stimulation of early peripheral axon regeneration by N
      propionylmannosamine in the presence of polysialyltransferase ST8SIA2.
AB  - The key enzyme of sialic acid (Sia) biosynthesis is the bifunctional UDP-N
      acetylglucosamine 2-epimerase/ManNAc kinase (GNE/MNK). It metabolizes the
      physiological precursor ManNAc and N-acyl modified analogues such as N
      propionylmannosamine (ManNProp) to the respective modified sialic acid.
      Polysialic acid (polySia) is a crucial compound for several functions in the
      nervous system and is synthesized by the polysialyltransferases ST8SIA2 and
      ST8SIA4. PolySia can be modified in vitro and in vivo by metabolic
      glycoengineering of the N-acyl side chain of Sia. In vitro studies show that the
      application of ManNProp increases neurite outgrowth and accelerates the re
      establishment of functional synapses. In this study, we investigate in vivo how
      ManNProp application might benefit peripheral nerve regeneration. In mice
      expressing axonal fluorescent proteins (thy-1-YFP), we transected the sciatic
      nerve and then replaced part of it with a sciatic nerve graft from non-expressing
      mice (wild-type mice or St8sia2(-/-) mice). Analyses conducted 5 days after
      grafting showed that systemic application of ManNProp (200 mg/kg, twice a day,
      i.p.), but not of physiological ManNAc (1 g/kg, twice a day, i.p.), significantly
      increased the extent of axonal elongation, the number of arborizing axons and the
      number of branches per regenerating axon within the grafts from wild-type mice,
      but not in those from St8sia2(-/-) mice. The results demonstrate that the
      application of ManNProp has beneficial effects on early peripheral nerve
      regeneration and indicate that the stimulation of axon growth depends on ST8SIA2
      activity in the nerve graft.

PMID- 25850643
TI  - [New short-acting local anaesthetics for spinal anaesthesia - Well-tried
      substances for ambulatory surgery].
AB  - More and more operative procedures are performed in an ambulatory setting. Many
      patients are denied spinal anaesthesia, although it provides several advantages.
      Innovative pharmaceutical formulations of well-tried local anaesthetics have
      created "new" substances that are ideal for ambulatory surgery due to their fast
      onset, short duration of action, and very low incidence of complications such as
      transient neurological symptoms (TNS). Both hyperbaric prilocaine 2% and
      preservative-free chloroprocaine 1% were recently approved for spinal application
      in Germany. Additional perioperative measures, such as the use of atraumatic,
      thin spinal needles (25 or 27G), restrictive volume management, and early patient
      mobilisation, lead to a further reduction of complications. The new S1 guideline
      of the German Society of Anaesthesiology and Intensive Care Medicine encourages
      us anaesthetists to use spinal anaesthesia more frequently in an ambulatory
      setting. 

PMID- 25850644
TI  - [Perioperative management of adult patients with obstructive sleep apnea].
AB  - Obstructive sleep apnea (OSA) is a common sleep related breathing disorder with
      an increasing prevalence. Most surgical patients with OSA have not been diagnosed
      prior to surgery and are at an increased risk of developing perioperative
      complications. Preoperative identification of these patients is important in
      order to take appropriate measures concerning a safe perioperative management.
      While the level of scientific evidence for single measures is still low, several
      steps seem prudent: Preoperatively, sedating medications should only be applied
      with extreme caution. Anesthetic management should focus on regional anesthetic
      techniques and reduction of systemic opioids. In the case of general anesthesia,
      an increased risk of a patient presenting with a difficult airway should be
      appreciated. The extent and duration of postoperative continuous monitoring has
      to be determined on an individual basis. A preoperatively existing therapy with
      continuous positive airway pressure should be continued postoperatively as soon
      as possible. Patients with OSA may be managed on an outpatient basis if certain
      requirements are met. 

PMID- 25850645
TI  - [Invasive emergency techniques - In-field-amputation].
AB  - On-scene invasive emergency procedures, such as Cricothyroidotomy, chest drain,
      intraosseous puncture or even in-field-amputation, are often unavoidable, when
      indicated, and present a major challenge for the emergency physician. Personal,
      temporal or local conditions are often unsuitable. Even with regular intervention
      by the Emergency Medical Service, "last resort" measures occur very infrequently,
      particularly in relation to paediatric emergencies. As well as theoretical
      training, practice-oriented course concepts are essential in order to achieve
      high quality in these procedures. This article presents the use of in-field
      amputation, with reference to indication, implementation, problems and risks. It
      is part of a series of four articles on the subject of invasive emergency
      techniques. 

PMID- 25850646
TI  - [Pssst ... AINS secrets! --now from bariatric surgery].

PMID- 25850647
TI  - [Patient autonomy and education -- for patients].

PMID- 25850648
TI  - [Patient autonomy and informed consent - ethical and legal issues].
AB  - Informing patients about the benefits and risks of and alternatives to proposed
      medical or surgical procedures is crucial to the patient-physician relationship.
      It is a legal and ethical precondition to a patient's informed consent to a
      course of action. Particularly in cases of serious illness and when there are far
      reaching implications for a patient's lifestyle, this process entails much more
      than just imparting information. Indeed, it is a dialogue through which the
      physician empowers the patient to reach a decision which reflects the patient's
      life situation and system of values. This process promotes patient autonomy.
      Studies have shown that this approach builds trust, increases patient
      satisfaction with health care and results in a higher degree of professional
      fulfilment for the physician. 

PMID- 25850649
TI  - [Health care power of attorney project at the University Hospital Frankfurt].
AB  - Under German law it is the patient alone who has the right to decide whether or
      not to undergo a particular medical procedure. Treating a patient without his or
      her consent always constitutes a serious infringement of the patient's
      constitutional right of self-determination as well as the right to physical
      integrity. By issuing a power of attorney in health care matters to a person he
      or she trusts, a patient can safeguard his or her rights in the event of
      incapacitation. At the University Hospital Frankfurt patients who are scheduled
      for major elective surgery are informed about the advantages of a health care
      power of attorney during premedication. The University Hospital has developed its
      own health care power of attorney form for patient use. In addition, patients
      have the option of receiving additional information about other types of health
      care advance directives, such as a living will.

PMID- 25850652
TI  - Potentiometric sensing array for monitoring aquatic systems.
AB  - Since aquatic environments are highly heterogeneous and dynamic, there is the
      need in aquatic ecosystem monitoring to replace traditional approaches based on
      periodical sampling followed by laboratory analysis with new automated techniques
      that allow one to obtain monitoring data with high spatial and temporal
      resolution. We report here on a potentiometric sensing array based on polymeric
      membrane materials for the continuous monitoring of nutrients and chemical
      species relevant for the carbon cycle in freshwater ecosystems. The proposed
      setup operates autonomously, with measurement, calibration, fluidic control and
      acquisition triggers all integrated into a self-contained instrument.
      Experimental validation was performed on an automated monitoring platform on lake
      Greifensee (Switzerland) using potentiometric sensors selective for hydrogen
      ions, carbonate, calcium, nitrate and ammonium. Results from the field tests were
      compared with those obtained by traditional laboratory analysis. A linear
      correlation between calcium and nitrate activities measured with ISEs and
      relevant concentrations measured in the laboratory was found, with the slopes
      corresponding to apparent single ion activity coefficients gamma(*)(Ca(2+)) =
      0.55(SD = 0.1mM) and gamma(*)(NO(3)(-)) = 0.75(SD = 4.7MUm). Good correlation
      between pH values measured with ISE and CTD probes (SD = 0.2 pH) suggests
      adequate reliability of the methodology.

PMID- 25850653
TI  - Alternative CD44 splicing identifies epithelial prostate cancer cells from the
      mesenchymal counterparts.
AB  - An epithelial to mesenchymal transition (EMT) has been shown to be a necessary
      precursor to prostate cancer metastasis. Additionally, the differential
      expression and splicing of mRNAs has been identified as a key means to
      distinguish epithelial from mesenchymal cells by qPCR, western blotting and
      immunohistochemistry. However, few markers exist to differentiate between these
      cells by flow cytometry. We previously developed two cell lines, PC3-Epi
      (epithelial) and PC3-EMT (mesenchymal). RNAseq was used to determine the
      differential expression of membrane proteins on PC3-Epi/EMT. We used western
      blotting, qPCR and flow cytometry to validate the RNAseq results. CD44 was one of
      six membrane proteins found to be differentially spliced between epithelial and
      mesenchymal PC3 cells. Although total CD44 was positive in all PC3-Epi/EMT cells,
      PC3-Epi cells had a higher level of CD44v6 (CD44 variant exon 6). CD44v6 was able
      to differentiate epithelial from mesenchymal prostate cancer cells using either
      flow cytometry, western blotting or qPCR.

PMID- 25850654
TI  - The prostaglandin D2 receptor CRTH2 regulates accumulation of group 2 innate
      lymphoid cells in the inflamed lung.
AB  - Group 2 innate lymphoid cells (ILC2s) promote type 2 cytokine-dependent immunity,
      inflammation, and tissue repair. Although epithelial cell-derived cytokines
      regulate ILC2 effector functions, the pathways that control the in vivo migration
      of ILC2s into inflamed tissues remain poorly understood. Here, we provide the
      first demonstration that expression of the prostaglandin D2 (PGD2) receptor CRTH2
      (chemoattractant receptor-homologous molecule expressed on Th2 cells) regulates
      the in vivo accumulation of ILC2s in the lung. Although a significant proportion
      of ILC2s isolated from healthy human peripheral blood expressed CRTH2, a smaller
      proportion of ILC2s isolated from nondiseased human lung expressed CRTH2,
      suggesting that dynamic regulation of CRTH2 expression might be associated with
      the migration of ILC2s into tissues. Consistent with this, murine ILC2s expressed
      CRTH2, migrated toward PGD2 in vitro, and accumulated in the lung in response to
      PGD2 in vivo. Furthermore, mice deficient in CRTH2 exhibited reduced ILC2
      responses and inflammation in a murine model of helminth-induced pulmonary type 2
      inflammation. Critically, adoptive transfer of CRTH2-sufficient ILC2s restored
      pulmonary inflammation in CRTH2-deficient mice. Together, these data identify a
      role for the PGD2-CRTH2 pathway in regulating the in vivo accumulation of ILC2s
      and the development of type 2 inflammation in the lung. 

PMID- 25850655
TI  - Characterization of host immunity during persistent vaginal colonization by Group
      B Streptococcus.
AB  - Streptococcus agalactiae (Group B Streptococcus, GBS) is a Gram-positive
      bacterium, which colonizes the vaginal tract in 10-30% of women. Colonization is
      transient in nature, and little is known about the host and bacterial factors
      controlling GBS persistence. Gaining insight into these factors is essential for
      developing therapeutics to limit maternal GBS carriage and prevent transmission
      to the susceptible newborn. In this work, we have used human cervical and vaginal
      epithelial cells, and our established mouse model of GBS vaginal colonization, to
      characterize key host factors that respond during GBS colonization. We identify a
      GBS strain that persists beyond a month in the murine vagina, whereas other
      strains are more readily cleared. Correspondingly, we have detected differential
      cytokine production in human cell lines after challenge with the persistent
      strain vs. other GBS strains. We also demonstrate that the persistent strain more
      readily invades cervical cells compared with vaginal cells, suggesting that GBS
      may potentially use the cervix as a reservoir to establish long-term
      colonization. Furthermore, we have identified interleukin-17 production in
      response to long-term colonization, which is associated with eventual clearance
      of GBS. We conclude that both GBS strain differences and concurrent host immune
      responses are crucial in modulating vaginal colonization. 

PMID- 25850657
TI  - Addressing the experimental variability associated with the microbiota.

PMID- 25850656
TI  - Epithelial-specific A2B adenosine receptor signaling protects the colonic
      epithelial barrier during acute colitis.
AB  - Central to inflammatory bowel disease (IBD) pathogenesis is loss of mucosal
      barrier function. Emerging evidence implicates extracellular adenosine signaling
      in attenuating mucosal inflammation. We hypothesized that adenosine-mediated
      protection from intestinal barrier dysfunction involves tissue-specific signaling
      through the A2B adenosine receptor (Adora2b) at the intestinal mucosal surface.
      To address this hypothesis, we combined pharmacologic studies and studies in mice
      with global or tissue-specific deletion of the Adora2b receptor. Adora2b(-/-)
      mice experienced a significantly heightened severity of colitis, associated with
      a more acute onset of disease and loss of intestinal epithelial barrier function.
      Comparison of mice with Adora2b deletion on vascular endothelial cells
      (Adora2b(fl/fl)VeCadCre(+)) or intestinal epithelia (Adora2b(fl/fl)VillinCre(+))
      revealed a selective role for epithelial Adora2b signaling in attenuating colonic
      inflammation. In vitro studies with Adora2b knockdown in intestinal epithelial
      cultures or pharmacologic studies highlighted Adora2b-driven phosphorylation of
      vasodilator-stimulated phosphoprotein (VASP) as a specific barrier repair
      response. Similarly, in vivo studies in genetic mouse models or treatment studies
      with an Adora2b agonist (BAY 60-6583) recapitulate these findings. Taken
      together, our results suggest that intestinal epithelial Adora2b signaling
      provides protection during intestinal inflammation via enhancing mucosal barrier
      responses. 

PMID- 25850658
TI  - Molecular characteristics of bap-positive Staphylococcus aureus strains from
      dairy cow mastitis.
AB  - The biofilm-associated protein (Bap) of Staphylococcus aureus is a high molecular
      weight cell-wall-anchored protein involved in biofilm formation, first described
      in bovine mastitis strains from Spain. So far, studies regarding Bap were mainly
      based on the Spanish strain V329 and its mutants, but no information on the
      genetic variability of bap-positive Staph. aureus strains is yet available in the
      literature. The present study investigated the molecular characteristics of 8 bap
      positive Staph. aureus strains from subclinical bovine mastitis, isolated in 5
      herds; somatic cell counts (SCC) of milk samples were also registered. Strains
      were characterised using MLST, SPA typing and microarray and the results were
      compared with V329. All isolates from this study and V329 were assigned to ST126,
      t605, but some molecular differences were observed. Only herd A and B strains
      harboured the genes for beta-lactams resistance; the leukocidin D/E gene, a type
      I site-specific deoxyribonuclease subunit, 3rd locus gene and serin-protease A
      and B were carried by all strains, but not by V329, while serin-protease E was
      absent in V329 and in another isolate. Four isolates and V329 harboured the
      fibronectin-binding protein B gene. SCC showed the highest value in the milk
      sample affected by the only strain carrying all the virulence factors considered.
      Potential large variability of virulence was evidenced among V329 and all bap
      positive Staph. aureus strains considered: the carriage of fnb could enhance the
      accumulation of biofilm, but the lack of lukD/E and splA, B or E might decrease
      the invasiveness of strain. 

PMID- 25850660
TI  - Diabetes: Therapy for gestational diabetes mellitus--time for a change?

PMID- 25850659
TI  - Local and systemic effects of the multifaceted epicardial adipose tissue depot.
AB  - Epicardial adipose tissue is a unique and multifaceted fat depot with local and
      systemic effects. This tissue is distinguished from other visceral fat depots by
      a number of anatomical and metabolic features, such as increased fatty acid
      metabolism and a unique transcriptome enriched in genes that are associated with
      inflammation and endothelial function. Epicardial fat and the heart share an
      unobstructed microcirculation, which suggests these tissues might interact. Under
      normal physiological conditions, epicardial fat has metabolic, thermogenic
      (similar to brown fat) and mechanical (cardioprotective) characteristics.
      Development of pathological conditions might drive the phenotype of epicardial
      fat such that it becomes harmful to the myocardium and the coronary arteries. The
      equilibrium between protective and detrimental effects of this tissue is fragile.
      Expression of the epicardial-fat-specific transcriptome is downregulated in the
      presence of severe and advanced coronary artery disease. Improved local
      vascularization, weight loss and targeted medications can restore the protective
      physiological functions of epicardial fat. Measurements of epicardial fat have
      several important applications in the clinical setting: accurate measurement of
      its thickness or volume is correlated with visceral adiposity, coronary artery
      disease, the metabolic syndrome, fatty liver disease and cardiac changes. On
      account of this simple clinical assessment, epicardial fat is a reliable marker
      of cardiovascular risk and an appealing surrogate for assessing the efficacy of
      drugs that modulate adipose tissues. 

PMID- 25850662
TI  - Obesity: Inhibiting PI3K reduces body weight in obese mice.

PMID- 25850663
TI  - Microfluidic droplet-based liquid-liquid extraction: online model validation.
AB  - Droplet-based liquid-liquid extraction in a microchannel was studied, both
      theoretically and experimentally. A full 3D mathematical model, incorporating
      convection and diffusion in all spatial directions along with the velocity
      profile, was developed to depict the governing transport characteristics of
      droplet-based microfluidics. The finite elements method, as the most common
      macroscale simulation technique, was used to solve the set of differential
      equations regarding conservation of moment, mass and solute concentration in a
      two-domain system coupled by interfacial surface of droplet-based flow pattern.
      The model was numerically verified and validated online by following the
      concentrations of a solute in two phases within the microchannel. The relative
      azobenzene concentration profiles in a methanol/n-octane two-phase system at
      different positions along the channel length were retrieved by means of a thermal
      lens microscopic (TLM) technique coupled to a microfluidic system, which gave
      results of high spatial and temporal resolution. Very good agreement between
      model calculations and online experimental data was achieved without applying any
      fitting procedure to the model parameters. 

PMID- 25850661
TI  - Islet alpha cells and glucagon--critical regulators of energy homeostasis.
AB  - Glucagon is secreted from islet alpha cells and controls blood levels of glucose
      in the fasting state. Impaired glucagon secretion predisposes some patients with
      type 1 diabetes mellitus (T1DM) to hypoglycaemia; whereas hyperglycaemia in
      patients with T1DM or type 2 diabetes mellitus (T2DM) is often associated with
      hyperglucagonaemia. Hence, therapeutic strategies to safely achieve euglycaemia
      in patients with diabetes mellitus now encompass bihormonal approaches to
      simultaneously deliver insulin and glucagon (in patients with T1DM) or reduce
      excess glucagon action (in patients with T1DM or T2DM). Glucagon also reduces
      food intake and increases energy expenditure through central and peripheral
      mechanisms, which suggests that activation of signalling through the glucagon
      receptor might be useful for controlling body weight. Here, we review new data
      that is relevant to understanding alpha-cell biology and glucagon action in the
      brain, liver, adipose tissue and heart, with attention to normal physiology, as
      well as conditions associated with dysregulated glucagon action. The feasibility
      and safety of current and emerging glucagon-based therapies that encompass both
      gain-of-function and loss-of-function approaches for the treatment of T1DM, T2DM
      and obesity is discussed in addition to developments, challenges and critical
      gaps in our knowledge that require additional investigation. 

PMID- 25850665
TI  - Advanced endoscopic therapeutics in Barrett's neoplasia: where are we now and
      where are we heading?
AB  - Over the last 10 years, there have been considerable changes in how we manage
      Barrett's neoplasia, with the shift away from conventional surgery and moving
      toward endotherapy for treating dysplasia and early cancer. In this editorial, we
      will review these changes and look forward to the possible developments which may
      occur over the next decade. 

PMID- 25850664
TI  - Fluoxetine induces input-specific hippocampal dendritic spine remodeling along
      the septotemporal axis in adulthood and middle age.
AB  - Fluoxetine, a selective serotonin-reuptake inhibitor (SSRI), is known to induce
      structural rearrangements and changes in synaptic transmission in hippocampal
      circuitry. In the adult hippocampus, structural changes include neurogenesis,
      dendritic, and axonal plasticity of pyramidal and dentate granule neurons, and
      dedifferentiation of dentate granule neurons. However, much less is known about
      how chronic fluoxetine affects these processes along the septotemporal axis and
      during the aging process. Importantly, studies documenting the effects of
      fluoxetine on density and distribution of spines along different dendritic
      segments of dentate granule neurons and CA1 pyramidal neurons along the
      septotemporal axis of hippocampus in adulthood and during aging are conspicuously
      absent. Here, we use a transgenic mouse line in which mature dentate granule
      neurons and CA1 pyramidal neurons are genetically labeled with green fluorescent
      protein (GFP) to investigate the effects of chronic fluoxetine treatment (18
      mg/kg/day) on input-specific spine remodeling and mossy fiber structural
      plasticity in the dorsal and ventral hippocampus in adulthood and middle age. In
      addition, we examine levels of adult hippocampal neurogenesis, maturation state
      of dentate granule neurons, neuronal activity, and glutamic acid decarboxylase-67
      expression in response to chronic fluoxetine in adulthood and middle age. Our
      studies reveal that while chronic fluoxetine fails to augment adult hippocampal
      neurogenesis in middle age, the middle-aged hippocampus retains high sensitivity
      to changes in the dentate gyrus (DG) such as dematuration, hypoactivation, and
      increased glutamic acid decarboxylase 67 (GAD67) expression. Interestingly, the
      middle-aged hippocampus shows greater sensitivity to fluoxetine-induced input
      specific synaptic remodeling than the hippocampus in adulthood with the stratum
      oriens of CA1 exhibiting heightened structural plasticity. The input-specific
      changes and circuit-level modifications in middle-age were associated with modest
      enhancement in contextual fear memory precision, anxiety-like behavior and
      antidepressant-like behavioral responses.

PMID- 25850666
TI  - Arrhythmias, syncopy, and sudden death.

PMID- 25850667
TI  - The first European Congress on e-Cardiology & e-Health.

PMID- 25850668
TI  - Occurrences and behaviors of naphthenic acids in a petroleum refinery wastewater
      treatment plant.
AB  - Naphthenic acids (NAs) are one class of compounds in wastewaters from petroleum
      industries that are known to cause toxic effects, and their removal from oilfield
      wastewater is an important challenge for remediation of large volumes of
      petrochemical effluents. The present study investigated occurrences and behaviors
      of total NAs and aromatic NAs in a refinery wastewater treatment plant, located
      in north China, which combined physicochemical and biological processes.
      Concentrations of total NAs were semiquantified to be 113-392 MUg/L in wastewater
      from all the treatment units, and the percentages of aromatic NAs in total NAs
      was estimated to be 2.1-8.8%. The mass reduction for total NAs and aromatic NAs
      was 15+/-16% and 7.5+/-24% after the physicochemical treatment, respectively.
      Great mass reduction (total NAs: 65+/-11%, aromatic NAs: 86+/-5%) was observed in
      the biological treatment units, and antiestrogenic activities observed in
      wastewater from physicochemical treatment units disappeared in the effluent of
      the activated sludge system. The distributions of mass fractions of NAs
      demonstrated that biodegradation via activated sludge was the major mechanism for
      removing alicyclic NAs, aromatic NAs, and related toxicities in the plant, and
      the polycyclic NA congener classes were relatively recalcitrant to
      biodegradation, which is a complete contrast to the preferential adsorption of
      NAs with higher cyclicity (low Z value). Removal efficiencies of total NAs were
      73+/-17% in summer, which were higher than those in winter (53+/-15%), and the
      seasonal variation was possibly due to the relatively high microbial
      biotransformation activities in the activated sludge system in summer (indexed by
      O3-NAs/NAs). The results of the investigations indicated that biotransformation
      of NA mixtures by the activated sludge system were largely affected by
      temperature, and employing an efficient adsorbent together with biodegradation
      processes would help cost-effectively remove NAs in petroleum effluents.

PMID- 25850669
TI  - Evolution in action: giant ankyrins awake.
AB  - Reporting in Developmental Cell, Stephan et al. (2015) demonstrate critical
      axonal and presynaptic functions from acquisition of an enormous exon by the
      Drosophila ank2 gene. They propose that highly elongated ank2-XL molecules,
      associated with the plasma membrane through spectrin and ank2-L, extend deep into
      the axoplasm to promote microtubule organization.

PMID- 25850670
TI  - A noisy tug of war: the battle between transcript production and degradation in
      the liver.
AB  - Genetically identical cells in culture often exhibit significant variations, or
      noise, in gene expression, largely due to transcriptional bursting. Halpern et
      al. (2015) have developed methods to study gene bursting in tissues to find that
      this transcriptional bursting also occurs in the mammalian liver and may
      contribute to functional plasticity in hepatocytes.

PMID- 25850671
TI  - Systemic organ wasting induced by localized expression of the secreted
      insulin/IGF antagonist ImpL2.
AB  - Organ wasting, related to changes in nutrition and metabolic activity of cells
      and tissues, is observed under conditions of starvation and in the context of
      diseases, including cancers. We have developed a model for organ wasting in adult
      Drosophila, whereby overproliferation induced by activation of Yorkie, the Yap1
      oncogene ortholog, in intestinal stem cells leads to wasting of the ovary, fat
      body, and muscle. These organ-wasting phenotypes are associated with a reduction
      in systemic insulin/IGF signaling due to increased expression of the secreted
      insulin/IGF antagonist ImpL2 from the overproliferating gut. Strikingly,
      expression of rate-limiting glycolytic enzymes and central components of the
      insulin/IGF pathway is upregulated with activation of Yorkie in the gut, which
      may provide a mechanism for this overproliferating tissue to evade the effect of
      ImpL2. Altogether, our study provides insights into the mechanisms underlying
      organ-wasting phenotypes in Drosophila and how overproliferating tissues adapt to
      global changes in metabolism.

PMID- 25850672
TI  - Malignant Drosophila tumors interrupt insulin signaling to induce cachexia-like
      wasting.
AB  - Tumors kill patients not only through well-characterized perturbations to their
      local environment but also through poorly understood pathophysiological
      interactions with distant tissues. Here, we use a Drosophila tumor model to
      investigate the elusive mechanisms underlying such long-range interactions.
      Transplantation of tumors into adults induces robust wasting of adipose, muscle,
      and gonadal tissues that are distant from the tumor, phenotypes that resemble the
      cancer cachexia seen in human patients. Notably, malignant, but not benign,
      tumors induce peripheral wasting. We identify the insulin growth factor binding
      protein (IGFBP) homolog ImpL2, an antagonist of insulin signaling, as a secreted
      factor mediating wasting. ImpL2 is sufficient to drive tissue loss, and insulin
      activity is reduced in peripheral tissues of tumor-bearing hosts. Importantly,
      knocking down ImpL2, specifically in the tumor, ameliorates wasting phenotypes.
      We propose that the tumor-secreted IGFBP creates insulin resistance in distant
      tissues, thus driving a systemic wasting response. 

PMID- 25850674
TI  - Balancing acts of two HEAT subunits of condensin I support dynamic assembly of
      chromosome axes.
AB  - Condensin I is a five-subunit protein complex that plays a central role in
      mitotic chromosome assembly and segregation in eukaryotes. To dissect its
      mechanism of action, we reconstituted wild-type and mutant complexes from
      recombinant subunits and tested their abilities to assemble chromosomes in
      Xenopus egg cell-free extracts depleted of endogenous condensins. We find that
      ATP binding and hydrolysis by SMC subunits have distinct contributions to the
      action of condensin I and that continuous ATP hydrolysis is required for
      structural maintenance of chromosomes. Mutant complexes lacking either one of two
      HEAT subunits produce abnormal chromosomes with highly characteristic defects and
      have contrasting structural effects on chromosome axes preassembled with the wild
      type complex. We propose that balancing acts of the two HEAT subunits support
      dynamic assembly of chromosome axes under the control of the SMC ATPase cycle,
      thereby governing construction of rod-shaped chromosomes in eukaryotic cells.

PMID- 25850673
TI  - A conserved phosphorylation switch controls the interaction between cadherin and
      beta-catenin in vitro and in vivo.
AB  - In metazoan adherens junctions, beta-catenin links the cytoplasmic tail of
      classical cadherins to the F-actin-binding protein alpha-catenin. Phosphorylation
      of a Ser/Thr-rich region in the cadherin tail dramatically enhances affinity for
      beta-catenin and promotes cell-cell adhesion in cell culture systems, but its
      importance has not been demonstrated in vivo. Here, we identify a critical
      phosphorylated serine in the C. elegans cadherin HMR-1 required for strong
      binding to the beta-catenin homolog HMP-2. Ablation of this phosphoserine
      interaction produces developmental defects that resemble full loss-of-function
      (Hammerhead and Humpback) phenotypes. Most metazoans possess a single gene for
      beta-catenin, which is also a transcriptional coactivator in Wnt signaling.
      Nematodes and planaria, however, have a set of paralogous beta-catenins; for
      example, C. elegans HMP-2 functions only in cell-cell adhesion, whereas SYS-1
      mediates transcriptional activation through interactions with POP-1/Tcf. Our
      structural data define critical sequence differences responsible for the unique
      ligand specificities of these two proteins.

PMID- 25850676
TI  - Assessment of heterogeneity in types of vegetables served by main household food
      preparers and food decision influencers.
AB  - OBJECTIVE: While vegetables are often studied as one food group, global measures
      may mask variation in the types and forms of vegetables preferred by different
      individuals. To explore preferences for and perceptions of vegetables, we
      assessed main food preparers based on their preparation of eight specific
      vegetables and mushrooms. DESIGN: An online self-report survey. SETTING: Ontario,
      Canada. Measures included perceived benefits and obstacles of vegetables,
      convenience orientation and variety seeking in meal preparation. SUBJECTS: Of the
      4517 randomly selected consumers who received the invitation, 1013 responded to
      the survey (22.4 % response). Data from the main food preparers were analysed (n
      756). RESULTS: Latent profile analysis indicated three segments of food
      preparers. More open to new recipes, the 'crucifer lover' segment (13 %) prepared
      and consumed substantially more Brussels sprouts, broccoli and asparagus than the
      other segments. Although similar to the 'average consumer' segment (54 %) in many
      ways, the 'frozen vegetable user' segment (33 %) used significantly more frozen
      vegetables than the other segments due to higher prioritization of time and
      convenience in meal preparation and stronger 'healthy=not tasty' perception.
      Perception of specific vegetables on taste, healthiness, ease of preparation and
      cost varied significantly across the three consumer segments. Crucifer lovers
      also differed with respect to shopping and cooking habits compared with the
      frozen vegetable users. CONCLUSIONS: The substantial heterogeneity in the types
      of vegetables consumed and perceptions across the three consumer segments has
      implications for the development of new approaches to promoting these foods.

PMID- 25850675
TI  - Transcriptome dynamics of the stomatal lineage: birth, amplification, and
      termination of a self-renewing population.
AB  - Developmental transitions can be described in terms of morphology and the roles
      of individual genes, but also in terms of global transcriptional and epigenetic
      changes. Temporal dissections of transcriptome changes, however, are rare for
      intact, developing tissues. We used RNA sequencing and microarray platforms to
      quantify gene expression from labeled cells isolated by fluorescence-activated
      cell sorting to generate cell-type-specific transcriptomes during development of
      an adult stem-cell lineage in the Arabidopsis leaf. We show that regulatory
      modules in this early lineage link cell types that had previously been considered
      to be under separate control and provide evidence for recruitment of individual
      members of gene families for different developmental decisions. Because stomata
      are physiologically important and because stomatal lineage cells exhibit
      exemplary division, cell fate, and cell signaling behaviors, this dataset serves
      as a valuable resource for further investigations of fundamental developmental
      processes.

PMID- 25850677
TI  - Assessing potato tuber diel growth by means of X-ray computed tomography.
AB  - The formation and development of belowground organs is difficult to study. X-ray
      computed tomography (CT) provides the possibility to analyse and interpret subtle
      volumetric changes of belowground organs such as tubers, storage roots and
      nodules. Here, we report on the establishment of a method based on a voxel
      dimension of 240 MUm and precision (standard deviation) of 30 MUL that allows
      interpreting growth differences among potato tubers happening within 3 h. Plants
      were not stressed by the application of X-ray radiation, which was shown both by
      morphological comparison with control plants and by analysis of lipid
      peroxidation as a measure of oxidative stress. Diel (24 h) tuber growth
      fluctuations of three potato genotypes were monitored in soil-filled pots of 10
      L. In contrast to the results from previous reports, most tubers grew at similar
      rates during day and night. Tuber growth was not related to the developmental
      stage of plants and tubers. Pronounced differences were observed between average
      growth rates in different tubers within a plant. These results are discussed in
      the context of restrictions of past methods to study tuber growth and in the
      context of their potential for the characterization of the formation and
      development of other belowground plant organs.

PMID- 25850678
TI  - immunoClust--An automated analysis pipeline for the identification of
      immunophenotypic signatures in high-dimensional cytometric datasets.
AB  - Multiparametric fluorescence and mass cytometry offers new perspectives to
      disclose and to monitor the high diversity of cell populations in the peripheral
      blood for biomarker research. While high-end cytometric devices are currently
      available to detect theoretically up to 120 individual parameters at the single
      cell level, software tools are needed to analyze these complex datasets
      automatically in acceptable time and without operator bias or knowledge. We
      developed an automated analysis pipeline, immunoClust, for uncompensated
      fluorescence and mass cytometry data, which consists of two parts. First, cell
      events of each sample are grouped into individual clusters. Subsequently, a
      classification algorithm assorts these cell event clusters into populations
      comparable between different samples. The clustering of cell events is designed
      for datasets with large event counts in high dimensions as a global unsupervised
      method, sensitive to identify rare cell types even when next to large
      populations. Both parts use model-based clustering with an iterative expectation
      maximization algorithm and the integrated classification likelihood to obtain the
      clusters. A detailed description of both algorithms is presented. Testing and
      validation was performed using 1) blood cell samples of defined composition that
      were depleted of particular cell subsets by magnetic cell sorting, 2) datasets of
      the FlowCAP III challenges to identify populations of rare cell types and 3) high
      dimensional fluorescence and mass-cytometry datasets for comparison with
      conventional manual gating procedures. In conclusion, the immunoClust-algorithm
      is a promising tool to standardize and automate the analysis of high-dimensional
      cytometric datasets. As a prerequisite for interpretation of such data, it will
      support our efforts in developing immunological biomarkers for chronic
      inflammatory disorders and therapy recommendations in personalized medicine.
      immunoClust is implemented as an R-package and is provided as source code from
      www.bioconductor.org.

PMID- 25850679
TI  - Physical characterization of wax/oil crystalline networks.
AB  - The objective of this research was to evaluate the physical properties of
      different types of wax/oil systems. Olive (OO), corn (CO), soybean (SBO),
      sunflower (SFO), safflower (SAFO), and canola (CAO) oils were mixed with
      sunflower oil wax (SFOW), paraffin wax (PW), and beeswax (BW) at different
      concentrations (1% to 10%). Results from this study show that the physical
      properties of wax/oil systems is affected not only by the concentration and type
      of wax used, but also by the type of oil used. In general, wax/oil systems
      formulated with SFOW generated crystalline networks with high enthalpies (1 to 22
      J/g) and high G' values (2 to 6 * 10(6) Pa) compared with the values obtained for
      BW and PW. SFOW crystalline networks were characterized by needle-like crystals
      independently of the wax concentrations and type of oil used. BW crystalline
      networks, however, were characterized by different crystal morphologies (needle
      like or spherulites) depending on the wax concentration and type of oil used. PW
      samples were characterized by a crystalline network formed by needle- and
      platelet-like crystals. Enthalpy values of BW and PW samples were similar (0.3 to
      20 J/g), but BW samples resulted in significantly higher (P < 0.05) G' values in
      the 5% and 10% samples with values of 3.9 * 10(6) and 6.1 * 10(5) Pa for 10% BW
      and PW, respectively.

PMID- 25850680
TI  - Electronic Spectroscopy of [FePAH](+) Complexes in the Region of the Diffuse
      Interstellar Bands: Multireference Wave Function Studies on [FeC6H6](+).
AB  - The low-energy states and electronic spectrum in the near-infrared-visible region
      of [FeC6H6](+) are studied by theoretical approaches. An exhaustive exploration
      of the potential energy surface of [FeC6H6](+) is performed using the density
      functional theory method. The ground state is found to be a (4)A1 state. The
      structures of the lowest energy states ((4)A2 and (4)A1) are used to perform
      multireference wave function calculations by means of the multistate complete
      active space with perturbation at the second order method. Contrary to the
      density functional theory results ((4)A1 ground state), multireference
      perturbative calculations show that the (4)A2 state is the ground state. The
      vertical electronic spectrum is computed and compared with the astronomical
      diffuse interstellar bands, a set of near-infrared-visible bands detected on the
      extinction curve in our and other galaxies. Many transitions are found in this
      domain, corresponding to d -> d, d -> 4s, or d -> pi* excitations, but few are
      allowed and, if they are, their oscillation strengths are small. Even though some
      band positions could match some of the observed bands, the relative intensities
      do not fit, making the contribution of the [Fe-C6H6](+) complexes to the diffuse
      interstellar bands questionable. This work, however, lays the foundation for the
      studies of polycyclic aromatic hydrocarbons (PAHs) complexed to Fe cations that
      are more likely to possess d -> pi* and pi -> pi* transitions in the diffuse
      interstellar bands domain. PAH ligands indeed possess a larger number of pi and
      pi* orbitals, respectively, higher and lower in energy than those of C6H6, which
      are expected to lead to lower energy d -> pi* and pi -> pi* transitions in
      [FePAH](+) than in [FeC6H6](+) complexes. 

PMID- 25850681
TI  - Dereplication: racing to speed up the natural products discovery process.
AB  - Covering: 1993-2014 (July)To alleviate the dereplication holdup, which is a major
      bottleneck in natural products discovery, scientists have been conducting their
      research efforts to add tools to their "bag of tricks" aiming to achieve faster,
      more accurate and efficient ways to accelerate the pace of the drug discovery
      process. Consequently dereplication has become a hot topic presenting a huge
      publication boom since 2012, blending multidisciplinary fields in new ways that
      provide important conceptual and/or methodological advances, opening up
      pioneering research prospects in this field. 

PMID- 25850682
TI  - Dramatic erythroid response to low-dose thalidomide in two patients with
      transfusion independent thalassemia and severe post-transfusional alloimmune
      hemolysis.

PMID- 25850683
TI  - Prediction of fruit and vegetable intake from biomarkers using individual
      participant data of diet-controlled intervention studies.
AB  - Fruit and vegetable consumption produces changes in several biomarkers in blood.
      The present study aimed to examine the dose-response curve between fruit and
      vegetable consumption and carotenoid (alpha-carotene, beta-carotene, beta
      cryptoxanthin, lycopene, lutein and zeaxanthin), folate and vitamin C
      concentrations. Furthermore, a prediction model of fruit and vegetable intake
      based on these biomarkers and subject characteristics (i.e. age, sex, BMI and
      smoking status) was established. Data from twelve diet-controlled intervention
      studies were obtained to develop a prediction model for fruit and vegetable
      intake (including and excluding fruit and vegetable juices). The study population
      in the present individual participant data meta-analysis consisted of 526 men and
      women. Carotenoid, folate and vitamin C concentrations showed a positive
      relationship with fruit and vegetable intake. Measures of performance for the
      prediction model were calculated using cross-validation. For the prediction model
      of fruit, vegetable and juice intake, the root mean squared error (RMSE) was
      258.0 g, the correlation between observed and predicted intake was 0.78 and the
      mean difference between observed and predicted intake was - 1.7 g (limits of
      agreement: - 466.3, 462.8 g). For the prediction of fruit and vegetable intake
      (excluding juices), the RMSE was 201.1 g, the correlation was 0.65 and the mean
      bias was 2.4 g (limits of agreement: -368.2, 373.0 g). The prediction models
      which include the biomarkers and subject characteristics may be used to estimate
      average intake at the group level and to investigate the ranking of individuals
      with regard to their intake of fruit and vegetables when validating
      questionnaires that measure intake.

PMID- 25850684
TI  - Gold Nanoparticle-Based Facile Detection of Human Serum Albumin and Its
      Application as an INHIBIT Logic Gate.
AB  - In this work, a facile colorimetric method is developed for quantitative
      detection of human serum albumin (HSA) based on the antiaggregation effect of
      gold nanoparticles (Au NPs) in the presence of HSA. The citrate-capped Au NPs
      undergo a color change from red to blue when melamine is added as a cross-linker
      to induce the aggregation of the NPs. Such an aggregation is efficiently
      suppressed upon the adsorption of HSA on the particle surface. This method
      provides the advantages of simplicity and cost-efficiency for quantitative
      detection of HSA with a detection limit of ~1.4 nM by monitoring the colorimetric
      changes of the Au NPs with UV-vis spectroscopy. In addition, this approach shows
      good selectivity for HSA over various amino acids, peptides, and proteins and is
      qualified for detection of HSA in a biological sample. Such an antiaggregation
      effect can be further extended to fabricate an INHIBIT logic gate by using HSA
      and melamine as inputs and the color changes of Au NPs as outputs, which may have
      application potentials in point-of-care medical diagnosis. 

PMID- 25850685
TI  - Effect of oxygen and glucose deprivation on VEGF and its receptors in
      microvascular endothelial cells co-cultured with mast cells.
AB  - The aim of this study was to determine the correlation between angiogenesis and
      the differential expression of vascular endothelial growth factor (VEGF) and its
      receptors in myocardial microvascular endothelial cells (MMVECs) co-cultured with
      mast cells (MCs) or mast cell granules (MCGs) under oxygen and glucose
      deprivation (OGD). MMVECs and MCs were isolated from Wistar rats. MCs
      spontaneously degranulated in OGD. The expression of VEGF peaked at 8 h and
      decreased from 16 h in OGD. However, the expression of its receptor, fms-like
      tyrosine kinase-1 (Flt-1), and fetal liver kinase-1 (Flk-1), decreased
      significantly, and angiogenic potential of MMVECs decreased in OGD. Expression of
      VEGF, Flt-1, and Flk-1 increased significantly when MMVECs were co-cultured with
      MCGs or active MCs, but MCs had only a limited ability to induce angiogenesis in
      OGD. The angiogenic potential of MMVECs cultured in OGD (even with MCGs) was
      inferior to that of MMVECs cultured under normoxic conditions. OGD have a
      profound effect on angiogenesis, which is more pronounced than the effect of MCs
      on angiogenesis. 

PMID- 25850686
TI  - Intensive Care Infection Score--A new approach to distinguish between infectious
      and noninfectious processes in intensive care and medicosurgical patients.
AB  - OBJECTIVES: Clinicians regularly encounter substantial time delays in diagnosing
      sepsis and administering appropriate antibiotic treatment. This study
      investigated the ability of the Intensive Care Infection Score (ICIS) to
      distinguish between infectious and noninfectious processes, and to assess the
      justified commencement of antibiotic therapy retrospectively, in line with
      hospital actual best practice and applied laboratory parameters. METHODS:
      Intensive-care unit (ICU) patients were enrolled in this retrospective,
      observational study. Clinical data and laboratory parameters were determined
      daily. The cohort was divided into infected and noninfected patient groups.
      RESULTS: Out of 172 ICU patients, including 72 postoperative patients, the
      predictive value for infection throughout the first 5 days in 'all patients' and
      the 'postoperative patient' group was highest for ICIS. An ICIS cut-off value of
      three could predict infection in postoperative patients with 82.9% sensitivity
      and 75.1% specificity. ICIS showed the lowest rate of potentially 'falsely
      encouraged' and 'discouraged' antibiotic therapies for noninfected and for septic
      postoperative patients, respectively, compared with C-reactive protein,
      procalcitonin and white blood cell levels. CONCLUSIONS: In the ICU, particularly
      for postoperative patients, ICIS is a reliable marker for the timely
      identification of infection. ICIS may qualify as a new decision support tool for
      antibiotic therapy, when interpreted within the clinical context.

PMID- 25850687
TI  - Capabilities of a mobile extracorporeal membrane oxygenation service for severe
      respiratory failure delivered by intensive care specialists.
AB  - We conducted a single-centre observational study of retrievals for severe
      respiratory failure over 12 months. Our intensivist-delivered retrieval service
      has mobile extracorporeal membrane oxygenation capabilities. Sixty patients were
      analysed: 34 (57%) were female and the mean (SD) age was 44.1 (13.6) years. The
      mean (SD) PaO2 /FI O2 ratio at referral was 10.2 (4.1) kPa and median (IQR
      [range]) Murray score was 3.25 (3.0-3.5 [1.5-4.0]). Forty-eight patients (80%)
      required veno-venous extracorporeal membrane oxygenation at the referring centre.
      There were no cannulation or extracorporeal membrane oxygenation-related
      complications. The median (IQR [range]) retrieval distance was 47.2 (14.9-77.0
      [2.3-342.0]) miles. There were no major adverse events during retrieval. Thirty
      seven patients (77%) who received extracorporeal membrane oxygenation survived to
      discharge from the intensive care unit and 36 patients (75%) were alive after six
      months. Senior intensivist-initiated and delivered mobile extracorporeal membrane
      oxygenation is safe and associated with a high incidence of survival. 

PMID- 25850688
TI  - Guns, Impulsive Angry Behavior, and Mental Disorders: Results from the National
      Comorbidity Survey Replication (NCS-R).
AB  - Analyses from the National Comorbidity Study Replication provide the first
      nationally representative estimates of the co-occurrence of impulsive angry
      behavior and possessing or carrying a gun among adults with and without certain
      mental disorders and demographic characteristics. The study found that a large
      number of individuals in the United States self-report patterns of impulsive
      angry behavior and also possess firearms at home (8.9%) or carry guns outside the
      home (1.5%). These data document associations of numerous common mental disorders
      and combinations of angry behavior with gun access. Because only a small
      proportion of persons with this risky combination have ever been involuntarily
      hospitalized for a mental health problem, most will not be subject to existing
      mental health-related legal restrictions on firearms resulting from a history of
      involuntary commitment. Excluding a large proportion of the general population
      from gun possession is also not likely to be feasible. Behavioral risk-based
      approaches to firearms restriction, such as expanding the definition of gun
      prohibited persons to include those with violent misdemeanor convictions and
      multiple DUI convictions, could be a more effective public health policy to
      prevent gun violence in the population.

PMID- 25850690
TI  - Schizotypal, Dissociative, and Imaginative Processes in a Clinical OCD Sample.
AB  - OBJECTIVE: Previous research in a nonclinical sample has suggested that
      schizotypal, dissociative, and imaginative processes may play a role in obsessive
      compulsive disorder (OCD) symptoms (Aardema & Wu, ). The present study aims to
      extend these findings in a clinical sample. METHOD: N = 75 adults (mean age =
      37.99; 61.3% female), meeting the Diagnostic and Statistical Manual of Mental
      Disorders, Fourth Edition, Text Revision, diagnostic criteria for OCD completed a
      battery of self-report questionnaires measuring schizotypal, dissociative, and
      imaginative processes. RESULTS: Hierarchical regression analyses revealed
      inferential confusion and dissociation to be the strongest predictors of OCD
      symptoms, replicating and extending the findings by Aardema and Wu ().
      CONCLUSION: Results support the notion that inferential confusion and
      dissociation are important variables to consider in understanding symptoms of OCD
      independently from obsessive beliefs and negative mood states.

PMID- 25850691
TI  - Difficulty in obtaining travel insurance after cancer.

PMID- 25850689
TI  - Modulation of the host innate immune and inflammatory response by translocated
      bacterial proteins.
AB  - Bacterial secretion systems play a central role in interfering with host
      inflammatory responses to promote replication in tissue sites. Many intracellular
      bacteria utilize secretion systems to promote their uptake and survival within
      host cells. An intracellular niche can help bacteria avoid killing by phagocytic
      cells, and may limit host sensing of bacterial components. Secretion systems can
      also play an important role in limiting host sensing of bacteria by translocating
      proteins that disrupt host immune signalling pathways. Extracellular bacteria, on
      the other hand, utilize secretion systems to prevent uptake by host cells and
      maintain an extracellular niche. Secretion systems, in this case, limit sensing
      and inflammatory signalling which can occur as bacteria replicate and release
      bacterial products in the extracellular space. In this review, we will cover the
      common mechanisms used by intracellular and extracellular bacteria to modulate
      innate immune and inflammatory signalling pathways, with a focus on translocated
      proteins of the type III and type IV secretion systems. 

PMID- 25850692
TI  - Regulatory T cells: Mechanisms of suppression and impairment in autoimmune liver
      disease.
AB  - There are three classic liver diseases with probable autoimmune etiology: primary
      biliary cirrhosis, primary sclerosing cholangitis, and autoimmune hepatitis. The
      occurrence of these autoimmune conditions is determined by the breakdown of
      immune-regulatory mechanisms that in health are responsible for maintaining
      immunological tolerance against self-antigens. Among the multiple T cell subsets
      with suppressive function, the regulatory T cells (Tregs), defined by the
      expression of CD4, the IL-2 receptor alpha chain (CD25), and the transcription
      factor FOXP3, have emerged as having a central role in maintaining immune
      tolerance to autoantigens. Tregs are equipped with an array of mechanisms of
      suppression, including the modulation of antigen presenting cell maturation and
      function, the killing of target cells, the disruption of metabolic pathways, and
      the production of anti-inflammatory cytokines. In all the three autoimmune liver
      diseases mentioned above, there is evidence pointing for either a reduced
      frequency and/or function of Tregs. Here, we review the definition, phenotypic
      characteristics, and mechanisms of suppression employed by Tregs and then we
      discuss the evidence available pointing to their impairment in patients with
      autoimmune liver disease.

PMID- 25850693
TI  - A novel polymeric drug delivery system for localized and sustained release of
      tacrolimus (FK506).
AB  - Despite substantial improvement in microsurgical techniques for nerve repair,
      recovery after peripheral nerve injury is usually incomplete. FK506, an FDA
      approved immunosuppressant, improves functional recovery and reinnervation
      following peripheral nerve injury in animal models. However, systemically
      delivered FK506 causes undesirable global immunosuppression. We have, therefore,
      engineered a biodegradable local delivery system for FK506 using fibrin gel as a
      drug reservoir that could be placed at a site of nerve injury. FK506 was
      incorporated into fibrin gel in solubilized, particulated, and poly(lactic-co
      glycolic) acid (PLGA) microspheres-encapsulated forms. A tunable release of FK506
      in the fibrin gel from days to weeks was observed with the rate of release being
      most rapid for the solubilized form and then the particulate form. The most
      prolonged period of release was seen with the PLGA microsphere-encapsulated form.
      As analyzed by in vitro dorsal root ganglion (DRG) neurite extension assay, PLGA
      microsphere encapsulation of FK506 did not alter the drug's properties and the
      released FK506 maintained its bioactivity over the entire period of release. This
      study suggests that local delivery of FK506 with fibrin hydrogel could be used to
      enhance peripheral nerve regeneration.

PMID- 25850694
TI  - Bacterial cellulose-hydroxyapatite composites with osteogenic growth peptide
      (OGP) or pentapeptide OGP on bone regeneration in critical-size calvarial defect
      model.
AB  - This study aimed to evaluate the potential of bacterial cellulose-hydroxyapatite
      (BC-HA) composites associated with osteogenic growth peptide (OGP) or
      pentapeptide OGP(10-14) in bone regeneration in critical-size calvarial defects
      in mice. In this study, the BC-HA, BC-HA-OGP, and BC-HA-OGP(10-14) membranes were
      analyzed at 3, 7, 15, 30, 60, and 90 days. In each period, the specimens were
      evaluated by micro-computed tomography (uCT), descriptive histology, gene
      expression of bone biomarkers by qPCR and VEGFR-2 (vascular endothelial growth
      factor) quantification by ELISA. Three days post-operative, Runx2, Tnfrsf11b and
      Bglap bone biomarkers were upregulated mainly by BC-HA OGP and BC-HA OGP(10-14)
      membranes, suggesting an acceleration of the osteoblast differentiation/activity
      with the use of these biomaterials. At 60 and 90 days, a high percentage of bone
      formation was observed by uCT for BC-HA and BC-HA OGP(10-14) membranes. High
      expression of some bone biomarkers, such as Alpl, Spp1, and Tnfrsf11b, was also
      observed for the same membranes on days 60 and 90. In conclusion, the BC-HA
      membrane promoted a better bone formation in critical-size mice calvarial
      defects. Nevertheless, incorporation of the peptides at the concentration of 10(
      9) mol L(-1) did not improve bone regeneration potential in the long-term.

PMID- 25850695
TI  - Risk Factors for Severe Hand-Foot-Mouth Disease in Children in Hainan, China,
      2011-2012.
AB  - The incidence of severe/fatal cases of hand-foot-mouth disease (HFMD) has
      increased in South Asia. In China, Hainan Province had the highest incidence of
      mortality associated with HFMD in 2011. This study investigated the risk factors
      for severe HFMD in Hainan. The HFMD survey database for Hainan Province for 2011
      and 2012 was analyzed, and the biological and behavioral characteristics of
      severe (n = 980) and nonsevere (n = 1679) HFMD were compared. The association
      between each explanatory variable and the severity of HFMD was investigated using
      a logistic regression model after adjusting for confounders. Human enterovirus 71
      infection, a peak body temperature >39 degrees C, living outside urban areas,
      visiting a village clinic, low birth weight, never breastfed, cared for by
      grandparents, and caregiver with <6 years of education were associated with
      severe HFMD. Individual characteristics that are generally shared by children in
      households of low socioeconomic status tended to increase the risk of severe
      HFMD. 

PMID- 25850696
TI  - Pathological findings and diagnostic implications of a rhesus macaque (Macacca
      mulatta) model of aerosol exposure to Burkholderia mallei (glanders).
AB  - Burkholderia mallei is a Gram-negative bacillus that causes a pneumonic disease
      known as glanders in equids and humans, and a lymphatic infection known as farcy,
      primarily in equids. With the potential to infect humans by the respiratory
      route, aerosol exposure can result in severe, occasionally fatal, pneumonia.
      Today, glanders infections in humans are rare, likely due to less frequent
      contact with infected equids than in the past. Acutely ill humans often have non
      specific clinical signs and in order to diagnose cases, especially in scenarios
      of multiple cases in an unexpected setting, rapid diagnostics for B. mallei may
      be critical. The pathogenesis of acute glanders in the rhesus macaque (Macaca
      mulatta) was studied as an initial effort to improve diagnostic methods. In the
      study described here, the diagnostic techniques of PCR, culture and
      histopathology were compared. The results indicated that PCR may provide rapid,
      non-invasive diagnosis of glanders in some cases. As expected, PCR results were
      positive in lung tissue in 11/12 acutely infected rhesus macaques, but more
      importantly in terms of diagnostic algorithm development, PCR results were
      frequently positive in non-invasive samples such as broncho-alveolar lavage or
      nasal swabs (7/12) and occasionally in blood (3/12). However, conventional
      bacterial culture failed to recover bacteria in many of these samples. The study
      showed that the clinical presentation of aerosol-exposed rhesus macaques is
      similar to descriptions of human glanders and that PCR has potential for rapid
      diagnosis of outbreaks, if not individual cases. 

PMID- 25850697
TI  - ASSOCIATIONS BETWEEN ULTRASOUND AND CLINICAL FINDINGS IN 87 CATS WITH URETHRAL
      OBSTRUCTION.
AB  - Urethral obstruction is a life-threatening form of feline lower urinary tract
      disease. Ultrasonographic risk factors for reobstruction have not been previously
      reported. Purposes of this retrospective cross-sectional study were to describe
      urinary tract ultrasound findings in cats following acute urethral obstruction
      and determine whether ultrasound findings were associated with reobstruction.
      Inclusion criteria were a physical examination and history consistent with
      urethral obstruction, an abdominal ultrasound including a full evaluation of the
      urinary system within 24 h of hospitalization, and no cystocentesis prior to
      ultrasound examination. Medical records for included cats were reviewed and
      presence of azotemia, hyperkalemia, positive urine culture, and duration of
      hospitalization were recorded. For medically treated cats with available outcome
      data, presence of reobstruction was also recorded. Ultrasound images were
      reviewed and urinary tract characteristics were recorded. A total of 87 cats met
      inclusion criteria. Common ultrasound findings for the bladder included echogenic
      urine sediment, bladder wall thickening, pericystic effusion, hyperechoic
      pericystic fat, and increased urinary echoes; and for the kidneys/ureters
      included pyelectasia, renomegaly, perirenal effusion, hyperechoic perirenal fat,
      and ureteral dilation. Six-month postdischarge outcomes were available for 61
      medically treated cats and 21 of these cats had reobstruction. No findings were
      associated with an increased risk of reobstruction. Ultrasonographic perirenal
      effusion was associated with severe hyperkalemia (P = 0.009, relative risk 5.75,
      95% confidence interval [1.54-21.51]). Findings supported the use of ultrasound
      as an adjunct for treatment planning in cats presented with urethral obstruction
      but not as a method for predicting risk of reobstruction. 

PMID- 25850698
TI  - Low-dose RUTF protocol and improved service delivery lead to good programme
      outcomes in the treatment of uncomplicated SAM: a programme report from Myanmar.
AB  - The treatment of uncomplicated severe acute malnutrition (SAM) requires
      substantial amounts of ready-to-use therapeutic food (RUTF). In 2009, Action
      Contre la Faim anticipated a shortfall of RUTF for their nutrition programme in
      Myanmar. A low-dose RUTF protocol to treat children with uncomplicated SAM was
      adopted. In this protocol, RUTF was dosed according to beneficiary's body weight,
      until the child reached a Weight-for-Height z-score of >=-3 and mid-upper arm
      circumference >=110 mm. From this point, the child received a fixed quantity of
      RUTF per day, independent of body weight until discharge. Specific measures were
      implemented as part of this low-dose RUTF protocol in order to improve service
      quality and beneficiary support. We analysed individual records of 3083 children
      treated from July 2009 to January 2010. Up to 90.2% of children recovered, 2.0%
      defaulted and 0.9% were classified as non-responders. No deaths were recorded.
      Among children who recovered, median [IQR] length of stay and weight gain were 42
      days [28; 56] and 4.0 g kg(-1) day(-1) [3.0; 5.7], respectively. Multivariable
      logistic regression showed that children older than 48 months had higher odds of
      non-response to treatment than younger children (adjusted odds ratio: 3.51, 95%
      CI: 1.67-7.42). Our results indicate that a low-dose RUTF protocol, combined with
      specific measures to ensure good service quality and beneficiary support, was
      successful in treating uncomplicated SAM in this setting. This programmatic
      experience should be validated by randomised studies aiming to test, quantify and
      attribute the effect of the protocol adaptation and programme improvements
      presented here. 

PMID- 25850699
TI  - Early and late maternal effects on hatching phenology of Heterocypris incongruens
      (Crustacea: Ostracoda).
AB  - In ephemeral ponds, the hatching asynchrony of resting eggs may be adaptive and
      the result of a maternal bet-hedging strategy. A mother can influence the progeny
      phenology through conditions experienced during life cycle even in early
      development stages. We investigated the consequences of a hatching delay for
      offspring and compared early and late maternal effects in a clonal lineage of
      Heterocypris incongruens. We used females from genetically identical, 40 months
      old, resting eggs that hatched, asynchronically, after a first (FI) or a second
      (SI) inundation event. Maternal origin (FI or SI) was considered an early effect
      involving the maternal response to hatching stimuli during the embryological
      dormant stage. Maternal age at deposition and egg size were considered late
      effects that account for maternal conditions during active stage. We compared
      size and development time of eggs produced by FI and SI females under laboratory
      condition (24 degrees C 12:12 L:D photoperiod). Maternal origin affected
      development time to adulthood which was later in FI than in SI females, and
      fecundity that was higher in FI than in SI females. SI eggs were smaller than FI
      eggs: size was affected by maternal age at deposition and was directly related to
      the egg development time. Development time varied from 1 to 117 days and was
      shorter in SI eggs than in FI eggs. Our results showed that maternal response
      during embryological stage affects the performance in successive active stages
      and suggested that hatching asynchrony may be considered a risk spread strategy.

PMID- 25850700
TI  - Determinants of elite-level air rifle shooting performance.
AB  - This study focused on identifying the most important factors determining
      performance in elite-level air rifle shooting technique. Forty international- and
      national-level shooters completed a simulated air rifle shooting competition
      series. From a total of 13 795 shots in 319 tests, shooting score and 17 aiming
      point trajectory variables were measured with an optoelectronic device and six
      postural balance variables were measured with force platform. Principal component
      analysis revealed six components in the air rifle shooting technique: aiming
      time, stability of hold, measurement time, cleanness of triggering, aiming
      accuracy, and timing of triggering. Multiple regression analysis identified four
      of those, namely stability of hold, cleanness of triggering, aiming accuracy, and
      timing of triggering as the most important predictors of shooting performance,
      accounting for 81% of the variance in shooting score. The direct effect of
      postural balance on performance was small, accounting for less than 1% of the
      variance in shooting score. Indirectly, the effect can be greater through a more
      stable holding ability, to which postural balance was correlated significantly (R
      = 0.55, P < 0.001). The results of the present study can be used in assessing
      athletes' technical strengths and weaknesses and in directing training programs
      on distinct shooting technical components.

PMID- 25850701
TI  - Moving droplets between closed and open microfluidic systems.
AB  - In electric-field-mediated droplet microfluidics, there are two distinct
      architectures - closed systems using parallel-plate electrodes and open systems
      using coplanar electrodes fabricated on an open substrate. An architecture
      combining both closed and open systems on a chip would facilitate many of the
      chemical and biological processes now envisioned for the laboratory on a chip. To
      accomplish such an integration requires a means to move droplets back and forth
      between the two. This paper presents an investigation of the requirements for
      such manipulation of both water and oil droplets. The required wetting conditions
      for a droplet to cross the open/closed boundary is revealed by a force balance
      analysis and predictions of this model are compared to experimental results.
      Water droplets can be moved between closed and open systems by electrowetting
      actuation; droplet detachment from the upper plate is facilitated by the use of
      beveled edge. The force model predicts that driving an oil droplet from a closed
      to an open structure requires an oleophobic surface. This prediction has been
      tested and confirmed using <100> silicon wafers made oleophobic by re-entrant
      microstructures etched into the surface. 

PMID- 25850702
TI  - Biocompatible capped iron oxide nanoparticles for Vibrio cholerae detection.
AB  - We report the studies relating to fabrication of an efficient immunosensor for
      Vibrio cholerae detection. Magnetite (iron oxide (Fe(3)O(4))) nanoparticles (NPs)
      have been synthesized by the co-precipitation method and capped by citric acid
      (CA). These NPs were electrophoretically deposited onto indium-tin-oxide (ITO)
      coated glass substrate and used for immobilization of monoclonal antibodies
      against Vibrio cholerae (Ab) and bovine serum albumin (BSA) for Vibrio cholerae
      detection using an electrochemical technique. The structural and morphological
      studies of Fe(3)O(4) and CA-Fe(3)O(4)/ITO were characterized by x-ray diffraction
      (XRD), transmission electron microscopy (TEM), Fourier transform infrared (FTIR)
      spectroscopy, and dynamic light scattering (DLS) techniques. The average
      crystalline size of Fe(3)O(4), CA-Fe(3)O(4) nanoparticles obtained were about 29
      +/- 1 nm and 37 +/- 1 nm, respectively. The hydrodynamic radius of the
      nanoparticles was found to be 77.35 nm (Fe(3)O(4)) and 189.51 nm (CA-Fe(3)O(4))
      by DLS measurement. The results of electrochemical response studies of the
      fabricated BSA/Ab/CA-Fe(2)O(3)/ITO immunosensor exhibits a good detection range
      of 12.5-500 ng mL(-1) with a low detection limit of 0.32 ng mL(-1), sensitivity
      0.03 Omega/ng ml(-1) cm(-2), and reproducibility more than 11 times.

PMID- 25850703
TI  - Relationship of Structural Characteristics to Biomechanical Profile in Normal,
      Keratoconic, and Crosslinked Eyes.
AB  - PURPOSE: To evaluate the correlation of corneal biomechanical parameters with
      structural characteristics in normal, keratoconic, and collagen crosslinked eyes.
      METHODS: A prospective observational study that included 50 normal, 100
      keratoconic, and 25 crosslinked eyes. All eyes were imaged using a Scheimpflug
      camera and an ocular response analyzer. The main outcome measures analyzed were
      central corneal thickness (CCT), corneal volume (CV), maximal keratometry (Kmax),
      corneal hysteresis (CH), and corneal resistance factor (CRF). RESULTS:
      Significant differences were noted among all 3 groups of eyes for CCT, CV, Kmax,
      CH, and CRF values (P < 0.05 by analysis of variance). CH and CRF correlated
      negatively (CH, r = -0.40; CRF, r = -0.44; both P < 0.0001) with the Pentacam
      topographic keratoconus classification. Both CH and CRF correlated positively
      with CCT and CV for the normal, keratoconic, and crosslinked eyes. In contrast,
      significant negative correlations were observed between CH, CRF, and Kmax in the
      keratoconic eyes (CH, r = -0.43; CRF, r = -0.53; both P < 0.0001), whereas no
      association was noted for the normal and crosslinked eyes. CONCLUSIONS: CH and
      CRF are influenced by the corneal structure, with higher values noted in corneas
      with greater thickness and volume. Corneal biomechanical parameters progressively
      decrease as the severity of keratoconus increases. After collagen crosslinking,
      the relationship of the corneal curvature to the biomechanical profile is similar
      to normal eyes.

PMID- 25850704
TI  - Calcified corneal nerves.
AB  - PURPOSE: To report a case of calcified corneal nerves in an eye with long
      standing diabetic eye disease. METHODS: This is a case report where the clinical
      diagnosis was made using a slit-lamp biomicroscope and confirmed using in vivo
      confocal microscopy. Photoslit-lamp images were taken for both eyes, and nerve
      thickness measurements made using ImageJ software. RESULTS: A 70-year-old British
      white woman showed band keratopathy in the right eye and dense white lines and
      dots in her left cornea on slit-lamp examination. The left corneal images had an
      appearance exactly similar to stromal nerves and terminal bulbs reported before.
      In vivo confocal microscopy (IVCM) of the left cornea showed hyperreflective and
      thickened stromal and sub-Bowman nerves and their characteristic termination in
      bulbous thickenings. CONCLUSIONS: Clinically detected corneal nerve calcification
      has not been described before. This report presents the direct visualization of
      calcified corneal nerves and their terminal bulbs and IVCM characteristics.

PMID- 25850705
TI  - Novel corneal piggyback technique for consecutive intraocular lens implantation
      and penetrating keratoplasty surgery.
AB  - PURPOSE: To report a novel "piggyback" penetrating keratoplasty technique
      performed in a patient with severe keratoconus. METHODS: A 43-year-old man
      underwent cataract surgery and a new "piggyback" penetrating keratoplasty (PKP)
      technique in his right eye, as he suffered from severe keratoconus and mature
      cataract due to severe atopic dermatitis. Under general anesthesia,
      phacoemulsification and aspiration (PEA), intraocular lens (IOL) implantation,
      and "piggyback" PKP while avoiding open-sky surgery was performed to prevent
      serious complications including IOL and vitreous prolapse. This PKP technique had
      been completed as a totally closed surgery. RESULTS: One year after "piggyback"
      PKP and cataract surgery, the grafted cornea remained clear and IOL was also well
      positioned. Best-corrected visual acuity improved from hand motions to 30/100.
      CONCLUSIONS: A novel "piggyback" PKP technique was successfully performed in a
      patient with severe keratoconus. The new "piggyback" corneal transplantation
      technique may become an indispensable tool for transplant surgeons who want to
      improve surgical safety and predictability.

PMID- 25850706
TI  - Cornea preservation time study: methods and potential impact on the cornea donor
      pool in the United States.
AB  - PURPOSE: The aim of this study was to describe the aims, methods, donor and
      recipient cohort characteristics, and potential impact of the Cornea Preservation
      Time Study (CPTS). METHODS: The CPTS is a randomized clinical trial conducted at
      40 clinical sites (70 surgeons) designed to assess the effect of donor cornea
      preservation time (PT) on graft survival 3 years after Descemet stripping
      automated endothelial keratoplasty (DSAEK). Eyes undergoing surgery for Fuchs
      endothelial corneal dystrophy or pseudophakic/aphakic corneal edema were
      randomized to receive donor corneas stored <=7 days or 8 to 14 days. Donor and
      patient characteristics, tissue preparation and surgical parameters, recipient
      and donor corneal stroma clarity, central corneal thickness, intraocular
      pressure, complications, and a reading center-determined central endothelial cell
      density were collected. Surveys were conducted to evaluate pre-CPTS PT practices.
      RESULTS: The 1330 CPTS donors were: 49% >60 years old, 27% diabetic, had a median
      eye bank-determined screening endothelial cell density of 2688 cells/mm, and 74%
      eye bank prepared for DSAEK. A total of 1090 recipients (1330 eyes including 240
      bilateral cases) had: median age of 70 years, were 60% female, 90% white, 18%
      diabetic, 52% phakic, and 94% had Fuchs endothelial corneal dystrophy. Before the
      CPTS, 19 eye banks provided PT data on 20,852 corneas domestically placed for
      DSAEK in 2010 to 2011; 96% were preserved <=7 days. Of 305 American Academy of
      Ophthalmology members responding to a pre-CPTS survey, 233 (76%) set their
      maximum PT preference at 8 days or less. CONCLUSIONS: The CPTS will increase
      understanding of factors related to DSAEK success and, if noninferiority of
      longer PT is shown, will have great potential to extend the available pool of
      endothelial keratoplasty donors.Clinical Trial Registration-URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT01537393.

PMID- 25850707
TI  - Sutureless anterior lamellar keratoplasty with phacoemulsification.
AB  - PURPOSE: To compare the results of microkeratome-assisted sutureless anterior
      lamellar keratoplasty (SALK) with and without phacoemulsification. METHODS: In
      this retrospective comparative interventional case series, patients with
      superficial anterior corneal opacity were divided into 2 groups. Eyes in group 1
      (n = 6) had associated cataract and underwent SALK with phacoemulsification
      surgery (SALK triple). Eyes in group 2 (n = 6) did not have cataract and
      underwent only anterior lamellar keratoplasty. A 200-MUm microkeratome head was
      used for host and donor cut. Fibrin glue was applied at the graft-host junction.
      Visual acuity, refractive error, topographic changes, and pachymetry were noted.
      RESULTS: Mean follow-up was 9 +/- 2.7 months. The best spectacle-corrected visual
      acuity (BSCVA) improved significantly over the preoperative value in both the
      groups at 1 month, 6 months, and the last follow-up (P = 0.028). The mean gain in
      BSCVA was 8.8 +/- 3.4 lines and 6.8 +/- 5.2 lines, respectively, for groups 1 and
      2 at the last follow-up, with no statistically significant difference in the
      BSCVA of both groups at the last follow-up (P = 0.80). There was no statistical
      difference at the last follow-up between the 2 groups with respect to spherical
      equivalent (P = 0.6), cylinder (P = 0.81), topographic astigmatism (P = 0.75),
      and graft thickness (P = 0.81). One patient in group 1 underwent graft rejection,
      which completely reversed with treatment. No cases of graft dislocation,
      infection, epithelial ingrowth, vascularization, or recurrence of primary
      pathology were noted in either group. CONCLUSIONS: SALK triple is an effective
      surgery for early visual rehabilitation of patients with superficial anterior
      corneal opacity and concomitant cataract.

PMID- 25850708
TI  - Prospective Randomized Trial Comparing Efficacy of Topical Loteprednol Etabonate
      0.5% Versus Cyclosporine-A 0.05% for Treatment of Dry Eye Syndrome Following
      Hematopoietic Stem Cell Transplantation.
AB  - PURPOSE: To evaluate the safety and efficacy of topical loteprednol etabonate
      (LE) 0.5% compared with cyclosporine A (CsA) 0.05% for the prophylaxis and
      treatment of dry eye syndrome (DES) after hematopoietic stem cell transplantation
      (HSCT). METHODS: Seventy-five patients were randomized to LE (n = 76 eyes of 38
      patients) or CsA (n = 74 eyes of 37 patients) pre-HSCT. Lissamine green and
      fluorescein staining, tear break-up time, tear osmolarity (Osm), Schirmer score
      (Sch), intraocular pressure, visual acuity, and Ocular Surface Disease Index were
      assessed pre-HSCT, 3, 6, 9, and 12 months post-HSCT. RESULTS: There were no
      differences in DES incidence (P = 0.22; log-rank test) or progression (P = 0.41;
      log-rank test) between the 2 treatment arms during the course of the study. Among
      eyes with no DES at enrollment, the Kaplan-Meier analysis yielded a 90% rate of
      DES development in cyclosporine-treated eyes and a 79% rate of DES development in
      LE-treated eyes by 12 months post-HSCT. The Kaplan-Meier analysis of eyes with
      DES at enrollment demonstrated a 38% rate of disease progression among
      cyclosporine-treated eyes and a 26% rate of disease progression among loteprednol
      treated eyes by 12 months. No patient in either group had an elevation of 10 mm
      Hg or greater from baseline at any study visit, and no patients had their
      treatment discontinued for elevation in intraocular pressure. CONCLUSIONS: Pre
      HSCT initiation of LE 0.5% appears to be safe and may be as effective as CsA 0.5%
      for the treatment and prophylaxis of DES following HSCT.

PMID- 25850709
TI  - Vitamin D versus placebo in improvement of endothelial dysfunction: a meta
      analysis of randomized clinical trials.
AB  - AIMS: The possible effect of vitamin D administration in humans on endothelial
      dysfunction (ED) still remains undetermined. The current meta-analysis was
      performed to evaluate if vitamin D could improve ED. METHODS: Randomized, double
      blind, and placebo-controlled clinical trials were identified by systematic
      search of the PubMed, the Cochrane Library, the Web of Science and the Scopus
      data bases, as well as different reviews and clinical trials articles. A random
      effects model was used to calculate the pooled overall effect on flow-mediated
      dilation (FMD) linked to the vitamin D administration. Meta-regression and
      subgroup analyses were performed to evaluate the impact of study characteristics
      on the effect of vitamin D administration on FMD. RESULTS: A total of eight
      studies with nine relevant study arms were identified. The obtained results of
      pooled analysis showed that vitamin D administration did not improve FMD (eight
      studies, 529 subjects; weighted mean difference (WMD): 0.96%, 95% CI: -1.24% to
      2.06%; P = 0.09). This was probably due to significant heterogeneity in between
      included trials (I(2) = 84%, P < 0.00001). On the other hand, subgroup analysis
      demonstrated that vitamin D improved FMD in trials that lasted <16 weeks; if
      systolic blood pressure (SBP) was higher than 140 mmHg and in trials where
      diastolic blood pressure (DBP) was <80 mmHg. CONCLUSION: Although the current
      evidence clearly demonstrates that in certain conditions vitamin D can improve
      ED, a larger number of clinical trials are needed to confirm this assumption to
      confirm or reject the final statement on this topic.

PMID- 25850712
TI  - Type 2 diabetes mellitus treatment patterns in U.S. nursing home residents.
AB  - BACKGROUND: The prevalence of type 2 diabetes mellitus (diabetes) in nursing home
      residents (NHRs) is increasing, concurrently with obesity and other comorbid
      conditions. NHR would benefit greatly from antidiabetic medications that would
      improve glycemic control and give a lower risk of hypoglycemia but that do not
      contribute to weight gain in obese individuals. OBJECTIVE: To examine the
      prescription patterns to NHRs with diabetes, including the use of newer
      injectable therapies such as glucagon-like peptide-1 (GLP-1) receptor agonists.
      METHODS: Treatment patterns of diabetes in NHR were analyzed using Minimum Data
      Set records and prescription claims from the Omnicare Senior Health Outcomes data
      repository (May 2011-September 2012). RESULTS: The prevalence of diabetes in this
      population of 229,283 NHRs was 35.4%. Among the 44,665 NHRs with diabetes and
      prescription claims data, the prevalence of obesity (40.3%) and multiple
      comorbidities (100%) was high. Approximately 20% of the NHRs with diabetes were
      aged <65 years. Overall, 20% of NHRs had diabetes that was untreated with
      medications during the study period. Insulin was the mainstay of treatment
      (>80%), followed by oral agents (54%). GLP-1 receptor agonist use was low (0.5%)
      and associated with poor treatment persistence. CONCLUSION: Considerations other
      than glycemic control may drive prescribing decisions, contrary to
      recommendations from the American Diabetes Association, American Medical
      Directors Association, and European Association for the Study of Diabetes.

PMID- 25850710
TI  - Flecainide exerts paradoxical effects on sodium currents and atrial arrhythmia in
      murine RyR2-P2328S hearts.
AB  - AIMS: Cardiac ryanodine receptor mutations are associated with catecholaminergic
      polymorphic ventricular tachycardia (CPVT), and some, including RyR2-P2328S, also
      predispose to atrial fibrillation. Recent work associates reduced atrial Nav 1.5
      currents in homozygous RyR2-P2328S (RyR2(S/S) ) mice with slowed conduction and
      increased arrhythmogenicity. Yet clinically, and in murine models, the Nav 1.5
      blocker flecainide reduces ventricular arrhythmogenicity in CPVT. We aimed to
      determine whether, and how, flecainide influences atrial arrhythmogenicity in
      RyR2(S/S) mice and their wild-type (WT) littermates. METHODS: We explored effects
      of 1 MUm flecainide on WT and RyR2(S/S) atria. Arrhythmic incidence, action
      potential (AP) conduction velocity (CV), atrial effective refractory period
      (AERP) and AP wavelength (lambda = CV * AERP) were measured using multi-electrode
      array recordings in Langendorff-perfused hearts; Na(+) currents (INa ) were
      recorded using loose patch clamping of superfused atria. RESULTS: RyR2(S/S)
      showed more frequent atrial arrhythmias, slower CV, reduced INa and unchanged
      AERP compared to WT. Flecainide was anti-arrhythmic in RyR2(S/S) but pro
      arrhythmic in WT. It increased INa in RyR2(S/S) atria, whereas it reduced INa as
      expected in WT. It increased AERP while sparing CV in RyR2(S/S) , but reduced CV
      while sparing AERP in WT. Thus, RyR2(S/S) hearts have low lambda relative to WT;
      flecainide then increases lambda in RyR2(S/S) but decreases lambda in WT.
      CONCLUSIONS: Flecainide (1 MUm) rescues the RyR2-P2328S atrial arrhythmogenic
      phenotype by restoring compromised INa and lambda, changes recently attributed to
      increased sarcoplasmic reticular Ca(2+) release. This contrasts with the
      increased arrhythmic incidence and reduced INa and lambda with flecainide in WT.

PMID- 25850711
TI  - Dynasore enhances the formation of mitochondrial antiviral signalling aggregates
      and endocytosis-independent NF-kappaB activation.
AB  - BACKGROUND AND PURPOSE: Dynasore has been used extensively as an inhibitor of
      clathrin-mediated endocytosis. While studying the role of endocytosis in LPS
      induced signalling events, we discovered that dynasore itself induced activation
      of NF-kappaB, independently of its effects on endocytosis and without involving
      the Toll-like receptor 4 signalling pathways. The purpose of this study was to
      characterize this novel effect and to explore the underlying mechanism of action.
      EXPERIMENTAL APPROACH: We utilized gel electrophoresis, microscopy, gene
      knockdown and luciferase-based promoter activity to evaluate the effect of
      dynasore on cell signalling pathways and to delineate the mechanisms involved in
      its effects, KEY RESULTS: Dynasore activated the NF-kappaB and IFN-beta pathways
      by activating mitochondrial antiviral signalling protein (MAVS). We showed that
      MAVS is activated by NOX/Rac and forms high molecular weight aggregates, similar
      to that observed in response to viral infection. We also demonstrated that
      dynasore-induced activation of JNK occurs downstream of MAVS and is required for
      activation of NF-kappaB and IFN-beta. CONCLUSION AND IMPLICATIONS: These findings
      demonstrate a novel effect of dynasore on cell signalling. We describe a novel
      Rac1-, ROS- and MAVS-mediated signalling cascade through which dynasore
      dramatically activates NF-kappaB, mimicking the viral induction of this key
      inflammatory signalling pathway. Our results call attention to the need for a
      broader interpretation of results when dynasore is used in its traditional
      fashion as an inhibitor of clathrin-mediated endocytosis. These results suggest
      the intriguing possibility that dynasore or one of its analogues might be of
      value as an antiviral therapeutic strategy or vaccine adjuvant.

PMID- 25850713
TI  - Farm to Fork Quantitative Risk Assessment of Listeria monocytogenes Contamination
      in Raw and Pasteurized Milk Cheese in Ireland.
AB  - The objective of this study was to model and quantify the level of Listeria
      monocytogenes in raw milk cheese (RMc) and pasteurized milk cheese (PMc) from
      farm to fork using a Bayesian inference approach combined with a quantitative
      risk assessment. The modeling approach included a prediction of contamination
      arising from the farm environment as well from cross-contamination within the
      cheese-processing facility through storage and subsequent human exposure. The
      model predicted a high concentration of L. monocytogenes in contaminated RMc
      (mean 2.19 log10 CFU/g) compared to PMc (mean -1.73 log10 CFU/g). The mean
      probability of illness (P1 for low-risk population, LR) and (P2 for high-risk
      population, HR, e.g., immunocompromised) adult Irish consumers following exposure
      to contaminated cheese was 7 * 10(-8) (P1 ) and 9 * 10(-4) (P2 ) for RMc and 7 *
      10(-10) (P1 ) and 8 * 10(-6) (P2 ) for PMc, respectively. In addition, the model
      was used to evaluate performance objectives at various stages, namely, the cheese
      making and ripening stages, and to set a food safety objective at the time of
      consumption. A scenario analysis predicted various probabilities of L.
      monocytogenes contamination along the cheese-processing chain for both RMc and
      PMc. The sensitivity analysis showed the critical factors for both cheeses were
      the serving size of the cheese, storage time, and temperature at the distribution
      stage. The developed model will allow food processors and policymakers to
      identify the possible routes of contamination along the cheese-processing chain
      and to reduce the risk posed to human health. 

PMID- 25850714
TI  - Listing of plenary, oral and poster presentations of the 36th annual meeting of
      the american brachytherapy society.

PMID- 25850715
TI  - Decreasing Transmembrane Segment Length Greatly Decreases Perfringolysin O Pore
      Size.
AB  - Perfringolysin O (PFO) is a transmembrane (TM) beta-barrel protein that inserts
      into mammalian cell membranes. Once inserted into membranes, PFO assembles into
      pore-forming oligomers containing 30-50 PFO monomers. These form a pore of up to
      300 A, far exceeding the size of most other proteinaceous pores. In this study,
      we found that altering PFO TM segment length can alter the size of PFO pores. A
      PFO mutant with lengthened TM segments oligomerized to a similar extent as wild
      type PFO, and exhibited pore-forming activity and a pore size very similar to
      wild-type PFO as measured by electron microscopy and a leakage assay. In
      contrast, PFO with shortened TM segments exhibited a large reduction in pore
      forming activity and pore size. This suggests that the interaction between TM
      segments can greatly affect the size of pores formed by TM beta-barrel proteins.
      PFO may be a promising candidate for engineering pore size for various
      applications. 

PMID- 25850716
TI  - Cross-beta Amyloid Nanohybrids Loaded With Cytochrome C Exhibit Superactivity in
      Organic Solvents.
AB  - The present study reports the development of a unique class of Cytochrome C
      (CytC)-loaded cross-beta amyloid nanohybrids. The peroxidase activity of the
      bound CytC increased up to two orders of magnitude in organic solvents compared
      to the activity of unbound CytC in water. The amyloid sequences used in the study
      feature the nucleating core (17) LVFF(21) of the beta amyloid (Abeta), which
      assembled to form homogenous fibers and nanotubes. The morphology and exposed
      surface of the amyloid nanohydrids critically modulated the CytC activity. A CytC
      Ac-KLVFFAE-NH2 hybrid featuring nanofiber morphology showed 308-fold higher
      activity than unbound CytC in water, which increased to 450-fold with the
      nanotube morphology of CytC-Ac-KLVFFAL-NH2 . Notably, activity declined
      substantially when the exposed surface charge was detuned by replacing lysine
      with histidine, thus underpinning the importance of surface charge. This enzyme
      amyloid nanohybrid system could facilitate the technological application of
      enzymes.

PMID- 25850717
TI  - Radiosynthesis and evaluation of 18F-labeled aliphatic phosphonium cations as a
      myocardial imaging agent for positron emission tomography.
AB  - INTRODUCTION: Lipophilic cations such as phosphonium cations penetrate the
      hydrophobic barriers of the plasma and mitochondrial membranes and accumulate in
      the mitochondria in response to negative inner-transmembrane potentials. The
      present study reports the radiosynthesis and evaluation of (18)F-labeled
      aliphatic triphenylphosphonium cations as a potential agent for myocardial
      imaging by using PET. MATERIALS AND METHODS: (7
      [(18)F]fluoroheptyl)triphenylphosphonium salt ([(18)F]3) and (8
      [(18)F]fluorooctyl)triphenylphosphonium salt ([(18)F]6) were radiolabeled by
      means of two-step nucleophilic substitution reactions. We measured the log P
      value of [(18)F]3 and [F]6 to assess the appropriate range of lipophilicity for
      their suitability as PET myocardial imaging agents. Normal rats were imaged with
      microPET after intravenous injection of 37 MBq of [(18)F]3 and [(18)F]6. To
      determine the pharmacokinetics, a region of interest was drawn around the heart,
      and time-activity curves of [(18)F]3 and [(18)F]6 were generated to obtain the
      counts per pixel per second. RESULTS: The radiolabeled compounds [(18)F]3 and
      [(18)F]6 were synthesized with 18-25% yield. The radiochemical purity was greater
      than 98% on the basis of the analytical high-performance liquid chromatography
      system, and the specific activity was greater than 160-170 Ci/mmol. The log P
      value of the tracers was 2.52 +/- 0.01 ([(18)F]3) and 2.91 +/- 0.02 ([(18)F]6).
      Myocardium-to-liver ratios of [(18)F]3 and [(18)F]6 were 2.59 and 1.07,
      respectively, 10 min after injection, whereas the myocardium-to-lung ratios were
      5.57 and 3.35, respectively. In addition, [(18)F]3 and [(18)F]6 showed intense,
      homogenous uptake in the myocardium. CONCLUSION: (18)F-labeled aliphatic
      phosphonium cations [(18)F]3 and [(18)F]6 might have potential as novel
      myocardial agents for PET and could prove useful in clinical cardiac PET/computed
      tomography applications.

PMID- 25850718
TI  - Low-dose CT and contrast-medium CT in hybrid PET/CT systems for oncologic
      patients.

PMID- 25850719
TI  - Special issue on lung disease and epigenetics. Preface.

PMID- 25850720
TI  - Stable and easily accessible functional dyes: dihydrotetraazaanthracenes as
      versatile precursors for higher acenes.
AB  - A series of new dihydrotetraazaanthracenes and one new dihydrotetraazatetracene
      as substances for applications in organoelectronic devices and as suitable
      building blocks for higher azaacenes was synthesised. The condensation of
      aromatic diamines with dichlorodicyanopyrazine led to these tricyclic/tetracyclic
      compounds. Syntheses of N-substituted phenylenediamines were developed to enable
      the introduction of multiple functional groups such as ester, amino, or nitro
      groups on the chromophoric system. Relationships between the structure and the
      spectroscopic properties could be derived from UV/Vis absorption and fluorescence
      spectroscopy, as well as by DFT and TD-DFT calculations of molecular and
      aggregate structures. The absorption spectra are dominated by pi-pi* transitions
      of the single molecules, whereas aggregation needs to be taken into account to
      obtain reasonable agreement between theory and experiment in certain cases.
      Single-crystal X-ray analyses were carried out to examine the morphology and
      solid packing effects. Finally, a dihydrotetraazaanthracene was used as a
      building-block to create a mesoionic octaazapentacene. 

PMID- 25850721
TI  - Using Joint Interviews to Add Analytic Value.
AB  - Joint interviewing has been frequently used in health research, and is the
      subject of a growing methodological literature. We review this literature, and
      build on it by drawing on a case study of how people make decisions about taking
      statins. This highlights two ways in which a dyadic approach to joint
      interviewing can add analytic value compared with individual interviewing. First,
      the analysis of interaction within joint interviews can help to explicate tacit
      knowledge and to illuminate the range of often hard-to-access resources that are
      drawn upon in making decisions. Second, joint interviews mitigate some of the
      weaknesses of interviewing as a method for studying practices; we offer a
      cautious defense of the often-tacit assumption that the "naturalness" of joint
      interviews strengthens their credibility as the basis for analytic inferences. We
      suggest that joint interviews are a particularly appropriate method for studying
      complex shared practices such as making health decisions. 

PMID- 25850722
TI  - Perceptions of Empowerment Within and Across Partnerships in Community-Based
      Participatory Research: A Dyadic Interview Analysis.
AB  - Although the concept of empowerment is a key principle of community-based
      participatory research (CBPR), little is known about how academic and community
      partners perceive empowerment during a CBPR process. CBPR partners' perceptions
      of the process were explored using semi-structured interviews with both partners
      in 10 CBPR partnerships that had completed projects addressing social
      determinants of health. Dyadic interview analysis was employed to understand
      dynamics within and across partnerships. Five partnerships showed no differences
      in perceptions of empowerment. Four had minor discrepancies. Only one partnership
      varied considerably between partners, where the community partner perceived less
      empowerment regarding determining the study topic and overall control, influence,
      and respect throughout the process. This article discusses implications of
      findings for CBPR. Evaluating partners' perceived empowerment throughout a CBPR
      project might reveal areas to adjust, as not all projects with quantifiably
      successful outcomes involve processes that are successful in terms of
      empowerment. 

PMID- 25850723
TI  - MicroRNA-155 in the Heart: The Right Time at the Right Place in the Right Cell.

PMID- 25850725
TI  - MicroRNA-101 inhibits rat cardiac hypertrophy by targeting Rab1a.
AB  - Cardiac hypertrophy is a primary pathological change associated with
      cardiovascular diseases. Dysregulated microRNAs are frequent in cardiovascular
      diseases and contribute to cardiac hypertrophy by regulating a series of targeted
      genes. In this study, a rat model of cardiac hypertrophy was created by
      transverse abdominal aortic constriction, and cardiomyocyte hypertrophy in
      cultured neonatal rat cardiomyocytes was induced using angiotensin II (AngII) to
      investigate the role of miR-101 in myocardial hypertrophy. We demonstrated that
      miR-101 was downregulated in both the transverse abdominal aortic constriction
      rat model and hypertrophic cardiac myocytes. The overexpression of miR-101 in
      neonatal rat cardiomyocytes, which was accompanied by a reduced Rab1a level,
      inhibits 3 cardinal features of cardiomyocyte hypertrophy: fetal gene expression,
      protein synthesis, and cell enlargement. Conversely, the downregulation of miR
      101 reverses these effects. Furthermore, the luciferase reporter system
      demonstrated that Rab1a is a target gene of miR-101, and the ectopic expression
      of Rab1a can reverse the cardiomyocyte hypertrophy inhibitory activity of miR
      101. Taken together, our findings identify miR-101 as an important regulator in
      cardiac hypertrophy and implicate the potential application of miR-101 in the
      therapy of cardiac hypertrophy. 

PMID- 25850724
TI  - MicroRNA-155 Exerts Cell-Specific Antiangiogenic but Proarteriogenic Effects
      During Adaptive Neovascularization.
AB  - BACKGROUND: Adaptive neovascularization after arterial occlusion is an important
      compensatory mechanism in cardiovascular disease and includes both the remodeling
      of pre-existing vessels to collateral arteries (arteriogenesis) and angiogenic
      capillary growth. We now aimed to identify regulatory microRNAs involved in the
      modulation of neovascularization after femoral artery occlusion in mice. METHODS
      AND RESULTS: Using microRNA-transcriptome analysis, we identified miR-155 as a
      downregulated microRNA during hindlimb ischemia. Correspondingly, inhibition of
      miR-155 in endothelial cells had a stimulatory effect on proliferation and
      angiogenic tube formation via derepression of its direct target gene angiotensin
      II type 1 receptor. Surprisingly, miR-155-deficient mice showed an unexpected
      phenotype in vivo, with a strong reduction of blood flow recovery after femoral
      artery ligation (arteriogenesis) dependent on the attenuation of leukocyte
      endothelial interaction and a reduction of proarteriogenic cytokine expression.
      Consistently, miR-155-deficient macrophages exhibit a specific alteration of the
      proarteriogenic cytokine expression profile, which is partly mediated by the
      direct miR-155 target gene SOCS-1. CONCLUSIONS: Our data demonstrate that miR-155
      exerts an antiangiogenic but proarteriogenic function in the regulation of
      neovascularization via the suppression of divergent cell-specific target genes
      and that its expression in both endothelial and bone marrow-derived cells is
      essential for arteriogenesis in response to hindlimb ischemia in mice.

PMID- 25850726
TI  - Mitochondrial ATP-sensitive potassium channel opening inhibits isoproterenol
      induced cardiac hypertrophy by preventing oxidative damage.
AB  - Cardiac hypertrophy is a chronic complex disease that occurs in response to
      hemodynamic load and is accompanied by oxidative stress and mitochondrial
      dysfunction. Mitochondrial ATP-sensitive K channels (mitoKATPs) have previously
      been shown to prevent oxidative cardiac damage under conditions of
      ischemia/reperfusion. However, the effect of these channels on cardiac
      hypertrophy has not been tested to date. In this study, we show that treatment of
      Swiss mice with isoproterenol (30 mg.kg.d) induces cardiac hypertrophy while
      significantly decreasing the levels of reduced protein thiols, glutathione,
      catalase, and superoxide dismutase activity, indicative of a condition of
      oxidative imbalance. Treatment with diazoxide (a mitoKATP opener, 5 mg.kg.d)
      normalized the levels of protein thiols and reduced glutathione, rescued
      superoxide dismutase activity, and significantly prevented cardiac hypertrophy.
      The protective effects of diazoxide were mitigated by the mitoKATP blockers 5
      hydroxydecanoate (5 mg.kg.d) and glibenclamide (3 mg.kg.d), demonstrating that
      they were related to activation of the channel. Taken together, our results
      establish that mitoKATP activation promotes very robust prevention of cardiac
      hypertrophy and associated oxidative imbalance and suggest that these channels
      can be important drug targets for the pharmacological control of cardiac
      hypertrophy. 

PMID- 25850727
TI  - Anagrelide treatment and cardiovascular monitoring in essential thrombocythemia.
      A prospective observational study.
AB  - In this prospective observational single-center study, 55 patients with essential
      thrombocythemia who were candidates for second line treatment with anagrelide
      (ANA) received a preliminary cardiovascular (CV) clinical, instrumental and
      biochemical evaluation (CV history and symptoms, CV risk factors, blood pressure,
      heart rate, ECG and ECHO-cardio parameters, Troponin I, NT-proBNP). After this in
      depth CV screening, 54 out of 55 patients were deemed to be fit for ANA
      treatment. Thirty-eight of the 55 patients received ANA treatment for a median of
      36 months (range 3-48), and were monitored using the same CV evaluation. Fourteen
      of these 38 patients manifested CV adverse events (10 palpitation, 4 edema, 2
      arterial hypertension, 2 acute myocardial infarction) that were not predicted by
      the in-depth CV evaluation, and that led to ANA withdrawal in only one case (non
      cardiac refractory edema). In conclusion, the planned in-depth CV evaluation did
      not appear to be necessary in ET patients to evaluate their suitability for ANA
      treatment, and, moreover, was not able to predict the occurrence of CV adverse
      events during ANA treatment. Nevertheless, the CV adverse events (mostly
      palpitations and edema) were easily managed by the hematologists, and required
      the cardiologist involvement in very few selected cases. 

PMID- 25850728
TI  - Question prompt list responds to information needs of myelodysplastic syndromes
      patients and caregivers.
AB  - Myelodysplastic syndromes (MDS) are heterogeneous hematopoietic malignancies,
      often poorly understood by patients. Our aim was to obtain the views of MDS
      patients and family caregivers about a targeted question prompt list's (QPL)
      potential utility, and to evaluate their information needs. This targeted QPL,
      which included 53 suggested questions patients may ask onco-haematologists, was
      developed. A self-administered questionnaire eliciting feedback about the QPL and
      assessing its perceived usefulness was mailed to all members of Australian and
      French patients' national MDS associations. Respectively, 301 MDS patients and 53
      caregivers responded. Most (76.4%) were satisfied with the information provided
      at MDS disclosure but would have liked more information about prognosis (69.3%).
      Consistently, the three most useful questions focused on the risk of leukaemic
      transformation, the impact of treatment on chances of survival and the severity
      of the MDS. The majority (62.9%) of both patients and caregivers perceived the
      QPL as 'absolutely' useful, particularly those who would have preferred more
      information about prognosis (adjusted odds ratio=2.3, 95% confidence interval
      [1.2-4.2], p=0.008). Our proposal of intervention through a QPL was generally
      welcomed and could particularly address specific MDS patient needs regarding
      prognosis information. 

PMID- 25850729
TI  - LFA-1-targeting Leukotoxin (LtxA; Leukothera(r)) causes lymphoma tumor regression
      in a humanized mouse model and requires caspase-8 and Fas to kill malignant
      lymphocytes.
AB  - Leukotoxin (LtxA) is a protein secreted from the oral bacterium Aggregatibacter
      actinomycetemcomitans. LtxA binds to the beta2 integrin lymphocyte-associated
      function antigen-1 (LFA-1) on human white blood cells (WBCs), resulting in cell
      death. LtxA is currently under investigation as a novel therapy (Leukothera((r)))
      for treating hematologic malignancies and autoimmune diseases. We show here that
      LtxA has potent in vivo anti-lymphoma activity in mice. LtxA caused complete
      regression of B-cell tumors and promoted long-term survival of mice. The
      mechanism of LtxA-mediated killing of malignant lymphocytes was further examined.
      We found that LtxA kills malignant lymphocytes by a novel mechanism requiring the
      death receptor Fas and caspase-8, but not Fas ligand (FasL) or caspase-9. We also
      determined that LFA-1 and Fas are closely associated on the cell surface and this
      proximity of LFA-1 and Fas could explain how signaling through an integrin can
      lead to cell death. In addition to LFA-1, this work reveals a second surface
      protein, Fas, that is critical for LtxA-mediated cell death. Knowledge of the
      mechanism of cell death induced by LtxA will facilitate the development and
      understanding of this potent experimental therapeutic agent.

PMID- 25850731
TI  - Treatment targets in emergency departments: nurses' views of how they affect
      clinical practice.
AB  - AIMS AND OBJECTIVES: To understand nurses' views and experiences of four-hour
      treatment targets in the emergency department and how this impacts clinical
      decision-making throughout acute secondary care hospitals. BACKGROUND: In many
      countries, national treatment targets in the emergency department have been
      introduced. However, research and a recent enquiry into poor clinical care in one
      hospital in the UK have highlighted that patient care may be compromised by the
      need to meet these targets. DESIGN: Qualitative descriptive study as part of a
      case study approach. METHODS: Semi-structured interviews were conducted with 31
      nurses working in UK secondary care hospitals which had an emergency department.
      Nurses were purposively sampled from three specialties: emergency arenas
      (emergency department, n = 5; medical assessment n = 4 surgical receiving n = 2)
      (n = 11), surgical wards (n = 11) and medical wards (n = 9). RESULTS: Nurses in
      emergency arenas reported considerable burden, in terms of a very high workload
      and pressure from senior staff to meet the target. Respondents reported that
      negative impact on patient care for the majority of patients, excluding the most
      sick, for whom emergency arena nurses reported that they ensured received
      appropriate treatment, regardless of breaching treatment targets. Around half of
      the nurses working outside emergency arenas felt pressure and amended their work
      practices to enable colleagues in emergency arenas to meet treatment targets.
      CONCLUSIONS: Four-hour targets were not viewed as clinically helpful by the
      majority of nurses, some of whom questioned their appropriateness for patient
      care. RELEVANCE TO CLINICAL PRACTICE: Policy makers and senior managers should
      consider the suitability of treatment targets in the emergency department,
      particularly in relation to working conditions for nurses and other health
      professionals and its potential for negative impacts on patient care. While
      targets remain in place, senior nurses and managers should support nurses who
      breach the target to provide optimum clinical care.

PMID- 25850730
TI  - Computational neuroimaging and population receptive fields.
AB  - Functional magnetic resonance imaging (fMRI) noninvasively measures human brain
      activity at millimeter resolution. Scientists use different approaches to take
      advantage of the remarkable opportunities presented by fMRI. Here, we describe
      progress using the computational neuroimaging approach in human visual cortex,
      which aims to build models that predict the neural responses from the stimulus
      and task. We focus on a particularly active area of research, the use of
      population receptive field (pRF) models to characterize human visual cortex
      responses to a range of stimuli, in a variety of tasks and different subject
      populations. 

PMID- 25850733
TI  - Bilateral Cortical Encephalomalacia in a Patient Implanted With Bilateral Deep
      Brain Stimulation for Alzheimer's Disease: A Case Report.

PMID- 25850732
TI  - Onset of Mild Cognitive Impairment in Parkinson Disease.
AB  - OBJECTIVE: Characterize the onset and timing of cognitive decline in Parkinson
      disease (PD) from the first recognizable stage of cognitively symptomatic PD-mild
      cognitive impairment (PD-MCI) to PD dementia (PDD). Thirty-nine participants
      progressed from PD to PDD and 25 remained cognitively normal. METHODS: Bayesian
      estimated disease-state models described the onset of an individual's cognitive
      decline across 12 subtests with a change point. RESULTS: Subtests measuring
      working memory, visuospatial processing ability, and crystalized memory changed
      significantly 3 to 5 years before their first nonzero Clinical Dementia Rating
      and progressively worsened from PD to PD-MCI to PDD. Crystalized memory deficits
      were the hallmark feature of imminent conversion of cognitive status. Episodic
      memory tasks were not sensitive to onset of PD-MCI. For cognitively intact PD,
      all 12 subtests showed modest linear decline without evidence of a change point.
      CONCLUSIONS: Longitudinal disease-state models support a prodromal dementia stage
      (PD-MCI) marked by early declines in working memory and visuospatial processing
      beginning 5 years before clinical diagnosis of PDD. Cognitive declines in PD
      affect motor ability (bradykinesia), working memory, and processing speed
      (bradyphrenia) resulting in PD-MCI where visuospatial imagery and memory
      retrieval deficits manifest before eventual development of overt dementia. Tests
      of episodic memory may not be sufficient to detect and quantify cognitive decline
      in PD.

PMID- 25850734
TI  - Introduction to a special issue on Skin disease, immune response and cytokines.

PMID- 25850736
TI  - (E)-Specific direct Julia-olefination of aryl alcohols without extra reducing
      agents promoted by bases.
AB  - An unprecedented base-promoted direct olefination of aryl alcohols with sulfones
      via a Julia-type reaction has been described. No extra reductants are needed for
      Julia reaction since alcohols work as double sources of aldehydes and the
      hydride. Generally high yields were given for both terminal and highly (E)
      selective internal olefins. 

PMID- 25850735
TI  - Anatomical considerations for implant placements in first maxillary molar
      extracted sites in East Asian patients.
AB  - PURPOSE: With the advent of cone-beam computed tomography (CBCT) for
      maxillofacial imaging, there has been a paradigm shift from two dimensional
      panoramic radiography to three dimensional imaging. This study investigated the
      microanatomy of the maxillary permanent first molar socket and its relationship
      to the floor of the maxillary sinus, especially for immediate or early implant
      placement. MATERIALS AND RESULTS: Sixty CBCT scans of 30 Malay and 30 Chinese
      subjects were selected from over 300 archived images. Ninety-five percent of the
      subjects had sinus floor extending anterior to the first molar, while 72% had the
      floor dipping between the roots. Seventy-five percent of the patients had inter
      radicular bone and almost 50% had intrusion of root apices into the floor of the
      maxillary sinus. The dimensions of the socket were as follows: the mean width was
      11.42 +/- 0.86 mm; the mean length was 7.70 +/- 0.56 mm; the mean height on the
      coronal plane was 6.48 +/- 3.77 mm while on the sagittal plane it was 6.85 +/-
      3.67 mm. CONCLUSIONS: Any implant length greater than the mean height of the
      socket (approximately 7 mm) has a fair chance of perforation into the maxillary
      sinus if placed without any additional adjunct procedures. In addition, 50% of
      the apices opened into the maxillary sinus, thereby risking the creation of
      perforations or root displacements into the maxillary sinus during exodontia
      mandating CBCT scanning prior to any surgical implant procedures.

PMID- 25850738
TI  - On the occurrence of a widespread contamination by herbicides of coral reef biota
      in French Polynesia.
AB  - Research has been conducted within the framework of the French Initiative for
      Coral Reefs (IFRECOR) to assess pesticide pollution levels in the coral reef
      trophic webs in French Polynesia. Unexpected widespread contamination by
      herbicides was found in algae, fishes and macro-invertebrates located at various
      levels of the reef trophic web. Concentrations in organisms investigated were for
      the majority below the lowest observable effect level and do not pose a dietary
      risk to native population who subsist on these fish. However, the widespread
      contamination may affect the reef ecosystem in the future as coral symbiotic
      algae, Symbidinium sp. (Dinophyta) are particularly sensitive to photosystem II
      herbicides, particularly the substituted urea and triazine derivatives. 

PMID- 25850739
TI  - Citric acid enhances the phytoextraction of chromium, plant growth, and
      photosynthesis by alleviating the oxidative damages in Brassica napus L.
AB  - Chromium (Cr) toxicity is widespread in crops grown on Cr-contaminated soils and
      has become a serious environmental issue which requires affordable strategies for
      the remediation of such soils. This study was performed to assess the performance
      of citric acid (CA) through growing Brassica napus in the phytoextraction of Cr
      from contaminated soil. Different Cr (0, 100, and 500 MUM) and citric acid (0,
      2.5, and 5.0 mM) treatments were applied alone and in combinations to 4-week-old
      seedlings of B. napus plants in soil under wire house condition. Plants were
      harvested after 12 weeks of sowing, and the data was recorded regarding growth
      characteristics, biomass, photosynthetic pigments, malondialdehyde (MDA),
      electrolytic leakage (EL), antioxidant enzymes, and Cr uptake and accumulation.
      The results showed that the plant growth, biomass, chlorophyll contents, and
      carotenoid as well as soluble protein concentrations significantly decreased
      under Cr stress alone while these adverse effects were alleviated by application
      of CA. Cr concentration in roots, stem, and leaves of CA-supplied plant was
      significantly reduced while total uptake of Cr increased in all plant parts with
      CA application. Furthermore, in comparison with Cr treatments alone, CA supply
      reduced the MDA and EL values in both shoots and roots. Moreover, the activity of
      superoxide dismutase (SOD), guaiacol peroxidase (POD), catalase (CAT), and
      ascorbate peroxidase (APX) in shoots and roots markedly increased by 100 MUM Cr
      exposure, while decreased at 500 MUM Cr stress. CA application enhanced the
      activities of antioxidant enzymes compared to the same Cr treatment alone. Thus,
      the data indicate that exogenous CA application can increase Cr uptake and can
      minimize Cr stress in plants and may be beneficial in accelerating the
      phytoextraction of Cr through hyper-accumulating plants such as B. napus.

PMID- 25850737
TI  - In situ remediation technologies for mercury-contaminated soil.
AB  - Mercury from anthropogenic activities is a pollutant that poses significant risks
      to humans and the environment. In soils, mercury remediation can be technically
      challenging and costly, depending on the subsurface mercury distribution, the
      types of mercury species, and the regulatory requirements. This paper introduces
      the chemistry of mercury and its implications for in situ mercury remediation,
      which is followed by a detailed discussion of several in situ Hg remediation
      technologies in terms of applicability, cost, advantages, and disadvantages. The
      effect of Hg speciation on remediation performance, as well as Hg transformation
      during different remediation processes, was detailed. Thermal desorption,
      electrokinetic, and soil flushing/washing treatments are removal technologies
      that mobilize and capture insoluble Hg species, while containment,
      solidification/stabilization, and vitrification immobilize Hg by converting it to
      less soluble forms. Two emerging technologies, phytoremediation and
      nanotechnology, are also discussed in this review. 

PMID- 25850740
TI  - Direct emissions of N2O, CO 2, and CH 4 from A/A/O bioreactor systems: impact of
      influent C/N ratio.
AB  - Direct emissions of N2O, CO2, and CH4, three important greenhouse gases (GHGs),
      from biological sewage treatment process have attracted increasing attention
      worldwide, due to the increasing concern about climate change. Despite the
      tremendous efforts devoted to understanding GHG emission from biological sewage
      treatment process, the impact of influent C/N ratios, in terms of chemical oxygen
      demand (COD)/total nitrogen (TN), on an anaerobic/anoxic/oxic (A/A/O) bioreactor
      system has not been investigated. In this work, the direct GHG emission from
      A/A/O bioreactor systems fed with actual sewage was analyzed under different
      influent C/N ratios over a 6-month period. The results showed that the variation
      in influent carbon (160 to 500 mg/L) and nitrogen load (35 to 95 mg/L)
      dramatically influenced pollutant removal efficiency and GHG production from this
      process. In the A/A/O bioreactor systems, the GHG production increased from 26-39
      to 112-173 g CO2-equivalent as influent C/N ratios decreased from 10.3/10.7 to
      3.5/3.8. Taking consideration of pollutant removal efficiency and direct biogenic
      GHG (N2O, CO2, and CH4) production, the optimum influent C/N ratio was determined
      to be 7.1/7.5, at which a relatively high pollutant removal efficiency and
      meanwhile a low level of GHG production (30.4 g CO2-equivalent) can be achieved.
      Besides, mechanical aeration turned out to be the most significant factor
      influencing GHG emission from the A/A/O bioreactor systems. 

PMID- 25850741
TI  - Relationships among bulk soil physicochemical, biochemical, and microbiological
      parameters in an organic alfalfa-rice rotation system.
AB  - The microbial communities of bulk soil of rice paddy fields under an ancient
      organic agriculture regimen, consisting on an alfalfa-rice rotation system, were
      characterized. The drained soil of two adjacent paddies at different stages of
      the rotation was compared before rice seeding and after harvesting. The
      relationships among the soil microbial, physicochemical, and biochemical
      parameters were investigated using multivariate analyses. In the first year of
      rice cropping, aerobic cultivable heterotrophic populations correlated with
      lineages of presumably aerobic bacteria (e.g., Sphingobacteriales,
      Sphingomonadales). In the second year of rice cropping, the total C content
      correlated with presumable anaerobic bacteria (e.g., Anaerolineae). Independently
      of the year of rice cropping, before rice seeding, proteolytic activity
      correlated positively with the cultivable aerobic heterotrophic and ammonifier
      populations, the soil catabolic profile and with presumable aerobes (e.g.,
      Sphingobacteriales, Rhizobiales) and anaerobes (e.g., Bacteroidales,
      Anaerolineae). After harvesting, strongest correlations were observed between
      cultivable diazotrophic populations and bacterial groups described as comprising
      N2 fixing members (e.g., Chloroflexi-Ellin6529, Betaproteobacteria,
      Alphaproteobacteria). It was demonstrated that chemical parameters and microbial
      functions were correlated with variations on the total bacterial community
      composition and structure occurring during rice cropping. A better understanding
      of these correlations and of their implications on soil productivity may be valid
      contributors for sustainable agriculture practices, based on ancient processes. 

PMID- 25850742
TI  - Highly stable rice-straw-derived charcoal in 3700-year-old ancient paddy soil:
      evidence for an effective pathway toward carbon sequestration.
AB  - Recalcitrant charcoal application is predicted to decelerate global warming
      through creating a long-term carbon sink in soil. Although many studies have
      showed high stability of charcoal derived from woody materials, few have focused
      on the dynamics of straw-derived charcoal in natural environment on a long
      timescale to evaluate its potential for agricultural carbon sequestration. Here,
      we examined straw-derived charcoal in an ancient paddy soil dated from ~3700
      calendar year before present (cal. year BP). Analytical results showed that soil
      organic matter consisted of more than 25% of charcoal in charcoal-rich layer.
      Similarities in morphology and molecular structure between the ancient and the
      fresh rice-straw-derived charcoal indicated that ancient charcoal was derived
      from rice straw. The lower carbon content, higher oxygen content, and obvious
      carbonyl of the ancient charcoal compared with fresh rice straw charcoal implied
      that oxidation occurred in the scale of thousands years. However, the dominant
      aromatic C of ancient charcoal indicated that rice-straw-derived charcoal was
      highly stable in the buried paddy soil due to its intrinsic chemical structures
      and the physical protection of ancient paddy wetland. Therefore, it may suggest
      that straw charcoal application is a potential pathway for C sequestration
      considering its longevity.

PMID- 25850743
TI  - Energy efficiency through integrated environmental management.
AB  - Integrated environmental management became an economic necessity after industrial
      development proved to be unsustainable without consideration of environmental
      direct and indirect impacts. Energy dependency and air pollution along with
      climate change grew into major challenges facing developed and developing
      countries alike. Thus, a new global market structure emerged and changed the way
      we do trade. The search intensified for alternatives to petroleum. However,
      scientists, policy makers, and environmental activists agreed to focus on
      strategic conservation and optimization of energy use. Environmental concerns
      will remain partially unaddressed with the current pace of consumption because
      greenhouse gas emissions will continue to rise with economic growth. This paper
      discusses energy efficiency, steady integration of alternative sources, and
      increased use of best available technologies. Energy criteria developed for
      environmental labeling certification are presented. Our intention is to encourage
      manufacturers and service providers to supply consumers with less polluting and
      energy-consuming goods and services, inform consumers of the environmental and
      energy impacts, and thereby instill sustainable and responsible consumption. As
      several programs were initiated in developed countries, environmental labeling
      requirements created barriers to many exports manufactured in developing
      countries, affecting current world trade and putting more pressure on countries
      to meet those requirements. Defining an institutional and legal framework of
      environmental labeling is a key challenge in implementing such programs for
      critical economic sectors like tourism, textiles, and food production where
      energy needs are the most important aspect to control. A case study of Tunisia
      and its experience with eco-labeling is presented. 

PMID- 25850744
TI  - Isolation and molecular characterization of multidrug-resistant halophilic
      bacteria from shrimp farm effluents of Parangipettai coastal waters.
AB  - Multidrug resistance of heterotrophic bacteria isolated from an aquaculture farm
      effluent in Parangipettai, at the southeastern coast of India, was investigated.
      In the initial screening, 27 antibiotic-resistant strains were isolated. All the
      strains were tested for antibiotic susceptibility against chloramphenicol with
      varying concentrations. From these, two highly resistant strains, i.e. S1 and S5,
      were isolated. The selected strains were identified by 16S ribosomal RNA (rRNA)
      sequencing techniques and confirmed as Bacillus pumilus and Bacillus flexus. Both
      the antibiotic-resistant strains were further utilized for multidrug
      susceptibility test by using various antibiotics. These two strains showed
      antibiotic resistance to 14 of 17 antibiotics tested. Both microdilution assay
      and well assay methods were used to determine the minimal inhibitory
      concentration (MIC) for the sensitive strains. Both the tests were shown to be
      almost similar. Our study highlights the occurrence of multidrug-resistant
      bacteria in the shrimp farm effluents. 

PMID- 25850745
TI  - Biodecolorization of recalcitrant dye as the sole sourceof nutrition using
      Curvularia clavata NZ2 and decolorization ability of its crude enzymes.
AB  - Extensive use of recalcitrant azo dyes in textile and paper industries poses a
      direct threat to the environment due to the carcinogenicity of their degradation
      products. The aim of this study was to investigate the efficiency of Curvularia
      clavata NZ2 in decolorization of azo dyes. The ability of the fungus to
      decolorize azo dyes can be evaluated as an important outcome as existing effluent
      treatment is unable to remove the dyes effectively. C. clavata has the ability to
      decolorize Reactive Black 5 (RB5), Acid Orange 7 (AO7), and Congo Red azo dyes,
      utilizing these as sole sources of carbon and nitrogen. Ultraviolet-visible (UV
      vis) spectroscopy and Fourier infrared spectroscopy (FTIR) analysis of the
      extracted RB5's metabolites along with desorption tests confirmed that the
      decolorization process occurred due to degradation and not merely by adsorption.
      Enzyme activities of extracellular enzymes such as carboxymethylcellulase
      (CMCase), xylanase, laccase, and manganese peroxidase (MnP) were also detected
      during the decolorization process. Toxicity expressed as inhibition of
      germination was reduced significantly in fungal-treated azo dye solution when
      compared with the control. The cultivation of C. clavata under sequential batch
      system also recorded a decolorization efficiency of above 90%. The crude enzyme
      secreted by C. clavata also showed excellent ability to decolorize RB5 solutions
      with concentrations of 100 ppm (88-92%) and 1000 ppm (70-77%) without redox
      mediator. This proved that extracellular enzymes produced by C. clavata played a
      major role in decolorization of RB5.

PMID- 25850746
TI  - Phytoremediation potential of Miscanthus * giganteus and Spartina pectinata in
      soil contaminated with heavy metals.
AB  - The aim of this work was to assess the suitability of Miscanthus * giganteus and
      Spartina pectinata link to Cu, Ni, and Zn phytoremediation. A 2-year microplot
      experiment with the tested grasses growing on metal-contaminated soil was carried
      out. Microplots with cement borders, measuring 1 * 1 * 1m, were filled with
      Haplic Luvisols soil. Simulated soil contamination with Cu, Ni, and Zn was
      introduced in the following doses in mg kg(-1): 0-no metals, Cu1-100, Cu2-200,
      Cu3-400, Ni1-60, Ni2-100, Ni3-240, Zn1-300, Zn2-600, and Zn3-1200. The
      phytoremediation potential of grasses was evaluated using a tolerance index (TI),
      bioaccumulation factor (BF), bioconcentration factor (BCF), and translocation
      factor (TF). S. pectinata showed a higher tolerance to soil contamination with
      Cu, Ni, and Zn compared to M. * giganteus. S. pectinata was found to have a high
      suitability for phytostabilization of Zn and lower suitability of Cu and Ni. M. *
      giganteus had a lower phytostabilization potential than S. pectinata. The
      suitability of both grasses for Zn phytoextraction depended on the age of the
      plants. Both grasses were not suitable for Cu and Ni phytoextraction. The
      research showed that one-season studies were not valuable for fully assessing the
      phytoremediation potential of perennial plants.

PMID- 25850748
TI  - Utilization of heavy metal-rich tannery sludge for sweet basil (Ocimum basilicum
      L.) cultivation.
AB  - Unlike food crops, essential oil-bearing crops in which the oil is extracted
      through hydro-distillation can be a suitable crop to be grown in heavy metal
      polluted soils as the oil does not carry any heavy metal. In a field experiment
      conducted at CIMAP, Lucknow, India during 2011 and 2012, influence of six doses
      of tannery sludge viz 0, 10, 20, 30, 40, and 50 t ha(-1) were tested, taking
      sweet basil (Ocimum basilicum) as the test crop. Maximum herb yield was obtained
      with the application of sludge at 20 t ha(-1). While in root, accumulation of Cd
      and Pb increased significantly up to 20 t ha(-1), Cr accumulation increased with
      increasing the dose of tannery sludge reaching maximum at 50 t ha(-1). Essential
      oil yield of basil (Ocimum basilicum) was significantly affected due to sludge
      application. Quality of essential oil, in term of chemical constituents, however,
      was marginally influenced due to tannery sludge application.

PMID- 25850747
TI  - Spatial distribution and temporal trends of mercury and arsenic in remote
      timberline coniferous forests, eastern of the Tibet Plateau, China.
AB  - An intensive investigation was conducted to study the spatial distribution and
      temporal variety trend of mercury and arsenic in plant tissue and soil profile in
      the eastern of the Tibet Plateau and to explore the possible sources of these two
      elements. At present, rare information is available on mercury (Hg) and arsenic
      (As) of timberline forests in the Tibet Plateau. Here, we present preliminary
      results on these two elements in leaves, twigs, root, litterfall, and soil.
      Geostatistical analyst of the ArcGIS 10.0 was used to determine the trait of
      spatial distribution of these two elements. Total arsenic (TAs) mean
      concentrations in the leaves, twigs, root, litterfall, and A- and C-layer soil
      ranged from 0.12 mg kg(-1) (n = 60), 0.35 mg kg(-1) (n = 60), 0.48 mg kg(-1) (n =
      42), 1.52 mg kg(-1) (n = 84), 16.51 mg kg(-1) (n = 69), and 26.72 mg kg(-1) (n =
      69), respectively. Total Hg (THg) mean concentrations in leaves, twigs, root,
      litterfall, and A- and C-layer soil were 0.0121 mg kg(-1) (n = 60), 0.0078 mg kg(
      1) (n = 60), 0.0171 mg kg(-1) (n = 42), 0.0479 mg kg(-1) (n = 84), 0.0852 mg kg(
      1) (n = 75), and 0.0251 mg kg(-1) (n = 75), respectively. In general, litterfall
      trended to accumulate high concentrations of Hg and As. Mercury in the timberline
      forest showed an increasing trend, whereas arsenic concentrations showed a
      decreasing trend in A-layer soil and an increasing trend in C-layer soil due to
      the easy mobile ability of As. Southwest and southeast monsoon could be the
      influencing factors, and Hg emission from India and China was the possible source
      of this study area through using a HYSPLIT (Hybrid Single-Particle Lagrangian
      Integrated Trajectory) model. It is believed that these observations may offer
      scientists and policymakers additional understanding of Hg and As concentrations
      in the remote timberline area, eastern of the Tibet Plateau.

PMID- 25850749
TI  - Combination therapy in hypertension: what are the best options according to
      clinical pharmacology principles and controlled clinical trial evidence?
AB  - Despite extensive debate about the first choice for treating essential
      hypertension, monotherapy effectively normalizes blood pressure (BP) values in
      only a limited number of hypertensive patients. Thus, the aim of combination
      therapy should always be to both improve BP control and to reduce cardiovascular
      events. Antihypertensive drugs can be effectively combined if they have different
      and complementary mechanisms of action. This is crucial to obtain additive BP
      lowering effects without impacting on tolerability. One typical combination is
      the association of drugs blocking and stimulating the renin-angiotensin system
      (RAS) (angiotensin-converting enzyme [ACE] inhibitor or angiotensin receptor
      blocker and calcium antagonist or diuretic, respectively). In contrast, some
      combinations (e.g., calcium antagonists plus diuretics or beta-blockers plus RAS
      blockers) have no additive BP-lowering effects, while other combinations (e.g.,
      clonidine plus alpha-1 receptor blockers) can have a negative interaction.
      Regardless, BP reduction is not the only mechanism that reduces cardiovascular
      risk. Scientific evidence indicates that some drug classes are better than others
      in this respect, and therefore some drug combinations are also better than
      others. The results of the ASCOT-BPLA and ACCOMPLISH trials suggested that an ACE
      inhibitor/calcium antagonist combination had better cardioprotective effects than
      beta-blocker/diuretic or ACE inhibitor/diuretic combinations. It is worth noting
      that no controlled clinical trials have used hard endpoints when investigating
      the effects of an angiotensin receptor blocker/calcium antagonist combination. In
      conclusion, combination therapy is needed for optimal antihypertensive
      management, with the first choice being an ACE inhibitor plus a calcium
      antagonist. This approach should improve BP control and provide better
      cardiovascular protection. 

PMID- 25850751
TI  - Gross hematuria caused by the nutcracker syndrome.

PMID- 25850750
TI  - Pharmacokinetics and Tolerability of the Novel Oral Prostacyclin IP Receptor
      Agonist Selexipag.
AB  - PURPOSE: Targeting the prostacyclin pathway is an effective treatment option for
      pulmonary arterial hypertension (PAH). Patients with PAH have a deficiency of
      prostacyclin and prostacyclin synthase. Selexipag is an orally available and
      selective prostacyclin receptor (IP receptor) agonist. Selexipag is hydrolyzed to
      its active metabolite ACT-333679, also a selective and potent agonist at the IP
      receptor. METHODS: In this phase I study the pharmacokinetics (PK) and
      tolerability of single and multiple ascending doses of selexipag were
      investigated in a double-blind, placebo-controlled manner in 64 healthy male
      subjects. An additional group of 12 subjects received an open-label dose of
      selexipag 400 MUg in the fasted condition and after a meal. RESULTS: Maximum
      plasma concentrations of selexipag and ACT-333679 were reached within 2.5 and 4
      h, respectively, with mean half-lives of 0.7-2.3 and 9.4-14.22 h. In the presence
      of food, exposure to ACT-333679 was decreased by 27 %. The most frequent adverse
      event was headache. Selexipag was well tolerated up to a single dose of 400 MUg
      and multiple doses of 600 MUg following an up-titration step. No relevant
      treatment-related effects on vital signs, clinical laboratory, and
      electrocardiogram (ECG) parameters were detected. CONCLUSION: Selexipag exhibits
      a good tolerability profile and PK properties that warrant further investigation.

PMID- 25850753
TI  - Supra-therapeutic tacrolimus concentrations associated with concomitant
      nicardipine in pediatric liver transplant recipients.
AB  - Tacrolimus is prescribed to prevent allograft rejection in pediatric liver
      transplant recipients; however, its metabolism through the cytochrome P-450
      enzyme system presents a multitude of challenges in regard to drug interactions.
      Here, we describe four children (ages 1.4-8.7 yr) who acutely developed supra
      therapeutic serum tacrolimus trough concentrations, despite standard dosing,
      while on concomitant nicardipine therapy following liver transplantation. Even
      though tacrolimus regimens were altered (dosage reductions and held doses), serum
      tacrolimus concentrations remained elevated. Resolution of high tacrolimus
      concentrations was achieved only after the discontinuation of nicardipine.
      Following the termination of nicardipine, all children eventually required dosage
      increases in their tacrolimus regimens to re-achieve target serum concentrations.
      We conclude that concomitant use of tacrolimus and nicardipine can result in high
      tacrolimus concentrations due to the inhibition of cytochrome p450 enzymes
      responsible for the metabolism of tacrolimus. We encourage clinicians to consider
      alternative antihypertensive options in children on tacrolimus therapy. If
      nicardipine therapy is necessary, we recommend a 50% reduction in tacrolimus dose
      and daily serum concentration monitoring.

PMID- 25850752
TI  - Competition between toxic and non-toxic Microcystis aeruginosa and its ecological
      implication.
AB  - The frequency of toxic cyanobacterial blooms has increased in recent decades, but
      the factors that regulate the dominance of toxin-producing cyanobacteria over non
      toxin-producing strains of one species are still obscure. This study examined the
      effects of temperature, light intensity, nitrate and phosphate on the dominance
      of MC-producing and non-MC-producing strains of Microcystis aeruginosa in
      monoculture and co-culture experiments. In the monoculture experiments, growth
      rates of the non-MC-producing strain were higher than those of the MC-producing
      strain under the same growth conditions. However, at the end of the co-culture
      experiments, the MC-producing strain became surprisingly dominant in all
      treatments except when treated with extreme low phosphate concentrations. Higher
      temperatures and nutrient levels can shift the dominance more quickly towards the
      toxic strain. The dominance may be explained by allelopathic interactions through
      allelochemicals and other secondary metabolites, but not MC. Environmental
      factors such as extremely low phosphate content may exert an indirect effect on
      strain dominance by changing the production of allelochemicals. Our findings
      highlight the complications in predicting competitive outcome for cyanobacterial
      strains in natural environments.

PMID- 25850755
TI  - Health literacy training for health professions students.
AB  - OBJECTIVE: This pilot project assessed the effectiveness of training health
      professionals in (1) readability assessment of written health materials, (2)
      plain language editing, and (3) formatting materials so they are easy to
      understand and use. METHODS: Over six semesters, five students participated in
      the project. Students were trained to assess document readability, confirm and
      interpret readability results and "stamp" the documents with results. Students
      then edited documents under supervision, via revised documents were re-assessed
      for readability and approved. Training was assessed through readability score
      comparison and exit interviews with students. RESULTS: Most original readability
      scores were 10th grade to college level. After editing, the average reading level
      of 73% was 6th grade or better. Students and supervisor rated skill levels as
      "proficient" at the end of the semester. CONCLUSION: To address the gap between
      document reading level and patients' reading ability, health documents should be
      assessed and edited for plain language. Working with patient documents from
      various health fields, our program effectively trained health professions
      students in these skills. PRACTICE IMPLICATIONS: Training health professions
      students in readability assessment and plain language editing can reduce literacy
      demands on patients and address the need for professionals with these skills.

PMID- 25850754
TI  - Immunostaining of ?Np63 (using the p40 antibody) is equal to that of p63 and
      CK5/6 in high-grade ductal carcinoma in situ of the breast.
AB  - As a result of breast cancer screening programs, high-grade ductal carcinoma in
      situ (DCIS) of the breast is diagnosed more often. Frequently, a DCIS diagnosis
      can only be made using immunohistochemical stains to visualize the myoepithelial
      layer in order to assess microinvasion. Standard markers for myoepithelial cells
      are CK5/6 and p63. An isoform of the latter, ?Np63, is recognized by a recently
      developed antibody, p40. Here, we compare the standard myoepithelial markers
      CK5/6 and p63 with p40. We immunostained full sections of tissue samples of 35
      high-grade DCIS and compared the staining pattern of CK5/6, p63 and p40 in tumour
      tissue and in normal glands. Staining patterns of myoepithelial cells for p63 and
      p40 were similar in terms of the percentage of stained nuclei. In all cases, p63
      was strongly expressed, while this was the case for p40 in 31 (89%) and
      moderately in 4 (11%) cases. All but one case (97%) showed a similar percentage
      of stained myoepithelial cells in comparing CK5/6 and p40 staining. CK5/6
      expression was heterogeneous and strong/moderate/weak in 60, 34 and 6 %
      respectively. Compared to surrounding normal glands, staining of myoepithelial
      cells for all three markers in the neoplastic lesion was attenuated. In high
      grade DCIS, p40 staining is highly specific for myoepithelial cells. Its staining
      pattern and intensity are equal to p63, which opens up its use for daily
      practice. Staining with p40 is less heterogeneous than that for CK5/6.

PMID- 25850756
TI  - Occupational therapists' shared decision-making behaviors with patients having
      persistent pain in a work rehabilitation context: A cross-sectional study.
AB  - OBJECTIVE: In a work rehabilitation context, we assessed occupational therapists'
      (OTs) shared decision-making (SDM) behaviors with individuals having persistent
      pain and explored factors influencing SDM behaviors. METHODS: A cross-sectional
      study that used audio-recordings of work rehabilitation consultations between OTs
      trained in SDM and a convenient sample of patients. Eligible patients were: off
      work for >=12 weeks due to persistent pain associated with a musculoskeletal
      disorder, starting a work rehabilitation program, and French speaking.
      Transcripts were analyzed using the Observing Patient Involvement in Shared
      Decision Making (OPTION) instrument and assessed patients' decisional conflict
      and socioeconomic status. RESULTS: Of 15 OTs trained in SDM, 11 (90% female),
      provided audiotaped SDM meetings with 37 patients (40.5% female; aged 18-62
      years). Their average OPTION score was 53.94 out of 100 (SD=9.68; range 35.42
      70.83), indicating basic skills. Significant factors associated with OPTION
      scores (R (2)adjusted=21.7%) were the interview length (p=0.008) and level of
      patient education (p=0.038). CONCLUSION: Basic SDM behaviors were integrated in
      the practice of OTs trained in SDM. PRACTICE IMPLICATIONS: Evaluating SDM
      behaviors is a step toward providing OTs with performance feedback toward
      achieving client-centered care.

PMID- 25850757
TI  - The effectiveness of dopamine agonists for treatment of neuropsychiatric symptoms
      post brain injury and stroke.
AB  - OBJECTIVE: Traumatic brain injury and stroke are among the leading causes of
      neurological disability worldwide. Although dopaminergic agents have long been
      associated with improvement of neuropsychiatric outcomes, to date much of the
      evidence to date has been in case reports and case series or open label trials.
      METHODS: We undertook a systematic review of double-blinded randomised controlled
      trials (RCT) to determine the effect of dopaminergic agents on pre-defined
      outcomes of (a) apathy; (b) psychomotor retardation; (c) behavioural management
      and (d) cognitive function. Databases searched were: Medline, EMBASE, and
      PsychInfo for human studies. The Cochrane Clinical Trials Database and the TRIP
      Medical database were also searched. All identified studies, were further hand
      searched. RESULTS: We identified six studies providing data on 227 participants,
      150 of whom received dopaminergic therapy. Trials were compromised by cross-over
      design, inadequate wash out period, small numbers and heterogeneous outcome
      measures. However one good quality RCT demonstrates the efficacy of amantadine in
      behavioural management. One further RCT shows methylphenidate-levodopa is
      efficacious for mood post-stroke. One study shows rotigotine to improve hemi
      inattention caused by prefrontal damage. CONCLUSION: Our systematic review
      demonstrates an evolving evidence base to suggest some benefits in agitation and
      aggression, mood and attentional deficits. However, there are key limitations of
      the studies undertaken to date involving small numbers of participants,
      heterogeneous outcome measures, and variable study designs. There is a need for
      on-going large prospective double-blind RCTs in these medications using
      standardised criteria and outcomes to fully understand their effectiveness in
      this patient group.

PMID- 25850758
TI  - Retraction Note to: Identification of gene expression profile in the rat brain
      resulting from acute alcohol intoxication.

PMID- 25850759
TI  - An appraisal on the occurrence of foot-and-mouth disease virus serotypes in
      cattle and buffaloes, Pakistan.
AB  - Foot-and-mouth disease (FMD) is a livestock disease that has serious economic
      repercussions. Here, we report the laboratory results for samples from suspected
      outbreaks that were sent for confirmation of FMD in Pakistan. From January 2010
      to December 2011, 132 suspected outbreaks were investigated, and samples from 58
      out of the 76 outbreaks sent to the National Veterinary Laboratory (NVL) were
      positive. The highest proportion of positives were of serotype O (65.52 %),
      followed by serotype A (24.14 %) and serotype Asia-1 (10.35 %), whereas amongst
      the samples sent to the World Reference Laboratory, Pirbright, UK (WRL), samples
      from 48 out of 56 outbreaks were confirmed to be FMD positive, with the following
      serotypes identified: O (56.25 %), Asia-1 (37.50 %) and A (6.25 %). The outbreaks
      affected cattle, buffalo and mixed (cattle and buffalo) herds at rates of 91, 70
      and 76 %, respectively. The trend of positive outbreaks was higher in the months
      of winter and late spring (November to April). Although the serotype O isolates
      and some of the serotype A isolates from the field samples resembled the vaccine
      strains (r-value >= 0.3), this was not the case for the Asia-1 isolates. These
      results help to improve our understanding of the occurrence and distribution of
      FMD in cattle and buffaloes in Pakistan and to provide baseline information for
      the FMD progressive control program in the country.

PMID- 25850760
TI  - Experimental infection of mice with bovine viral diarrhea virus.
AB  - The objective of this study was to test the ability of bovine viral diarrhea
      virus (BVDV) to infect mice. Two mice each were either mock infected or
      inoculated with one of three BVDV strains by the intraperitoneal (IP) (n = 8) or
      intranasal (IN) (n = 8) route. All mice were euthanized at day 7 postinfection
      (p.i.). None of the infected mice exhibited any clinical signs of illness;
      however, the tissues harvested after BVDV challenge showed significant
      histopathological changes. Blood samples from five mice that were injected IP and
      one mouse that was inoculated IN were positive for BVDV by reverse transcription
      polymerase chain reaction (RT-PCR). Immunohistochemistry (IHC) was used to assess
      the presence of viral antigen in the organs of mice infected with three BVDV
      strains. In IP-injected mice, BVDV antigen was detected in the spleen (5/6),
      mesenteric lymph nodes (4/6), lymphatic tissue of the lung (3/6), lung (1/6), and
      stomach (1/6) of the infected mice; however, it was not detected in the liver
      (0/6) or kidney (0/6). In IN-inoculated mice, BVDV antigen was detected in the
      lung and mesenteric lymph nodes of one BVDV-infected mouse but was not detected
      in other tissues. The results of this study suggest that the spleen is the most
      reliable tissue for BVDV antigen detection using IHC in the IP-injected group.
      Our study demonstrates that mice can be infected by BVDV. This is the first
      report of BVDV infection in mice.

PMID- 25850761
TI  - Polymorphisms in the retinoic acid-1 like-receptor family of genes and their
      association with clinical outcome of dengue virus infection.
AB  - Polymorphisms in the DDX58 and IFIH1 genes, which code for the retinoic acid
      inducible gene-1 protein and myeloid differentiation factor (MDA) 5, were
      investigated in 120 dengue (DEN) cases (88 dengue fever [DF] cases and 32 dengue
      hemorrhagic fever [DHF] cases) and 109 healthy controls (HCs) to investigate
      their association with dengue. The results revealed a lower carrier frequency of
      the DDX58 rs3205166 G allele in DEN than in HCs and a higher frequency of the
      DDX58 rs669260 T/C genotype in DHF than in DF cases (P = 0.043, OR with 95 % CI
      3.358 [1.038-10.861]). This suggests that polymorphisms in DDX58 gene influence
      the clinical outcome of DENV infection.

PMID- 25850762
TI  - [Respiratory emergencies and airway management in children].
AB  - Respiratory emergencies in children are frequent and are caused by the specific
      airway anatomy and the susceptibility for infections.This article reviews the
      specific approach to pediatric airway management. According to the ABC guidelines
      of the European Resuscitation Council, the described algorithm should help to
      identify, classify, and treat such emergencies, giving those with less pediatric
      experience a tool for the management of respiratory illness in children. Focus is
      on the emergency care of the most common diseases in this age group. 

PMID- 25850764
TI  - Using Strictosidine Synthase to Prepare Novel Alkaloids.
AB  - The Pictet-Spenglerasestrictosidine synthase (STR) has been characterized as the
      central enzyme in the biosynthesis of around 2000 monoterpenoid indole alkaloids
      in plants. In the light of a high therapeutic value and huge scaffold diversity
      these alkaloids represent, STR as an enzyme has attracted great attentions in
      recent years, intending to be utilized in the formation of new interesting
      alkaloids with unusual substitution pattern or even with novel scaffolds. For
      outlining the application potential that STR possesses, together with insight
      into the reaction mechanism catalyzed by STR, strategies and methods for
      exploring the applicability of STR have been updated in this article by taking R.
      serpertina STR(RS-STR) and C. roseus.STR (CR-STR) as representative models,
      followed by introducing the latest released complex structures of RS-STR with new
      substrates. Examples provided here, including substrate scaffold tailoring, X-ray
      crystal complex structure comparison, protein engineering and biosynthetic
      pathway reprogramming, pave the way to finally construct novel alkaloids
      libraries by chemo-enzymatic approaches.

PMID- 25850763
TI  - [Aspiration and pneumonia risk after preclinical invasive resuscitation:
      Endotracheal intubation and supraglottic airway management with the laryngeal
      tube S].
AB  - BACKGROUND: Laryngeal tubes (LT) have substantially facilitated emergency airway
      management. However, it remains unclear whether LTs provide comparable protection
      against aspiration or even higher rates of aspiration and pneumonia compared to
      endotracheal intubation (ET) as the former gold standard. METHODS: The indices
      for aspiration and early onset pneumonia in patients after preclinical airway
      management by either LT or ET were retrospectively analyzed. Furthermore, in
      hospital mortality was analyzed. RESULTS: A total of 90 patients with invasive
      ventilation by either ET (n = 69) or LT (n = 21) were analyzed. Patients were
      excluded if indication for ventilation was pneumonia, aspiration, drowning, or if
      they had preexisting tracheotomy. The ET and LT groups did not differ regarding
      age (ET: 62 +/- 16 years, LT: 64 +/- 8 years, p = 0.56), female gender (ET:
      23.2%, LT: 33.3%, p = 0.25), or first paO2/FIO2 (ET: 300 +/- 164, LT: 342 +/-
      178, p = 0.3). The majority of patients were survivors of out-of-hospital cardiac
      arrest (OHCA, 72.2%), with a significantly higher OHCA rate in the LT group (LT:
      95.2% ET: 65.2%, p = 0.006). Analysis for radiological or endoscopic evidence of
      pulmonary aspiration revealed a higher aspiration rate in the ET group (43.5%,
      LT: 23.8%, p = 0.08), especially after OHCA (ET: 48.9%, LT: 20%, p = 0.025). In
      parallel, early onset pneumonia as a correlate for microaspiration in patients
      without evident aspiration was observed more frequently in ET patients (41% vs.
      25%, p = 0.21). In OHCA patients without aspiration, rates of pneumonia were
      similar (ET: 26.1%, LT: 25%; p = 0.62). Analysis of in-hospital mortality showed
      significantly higher mortality in the LT group (57.1% vs 30.4%, p = 0.026). Also
      in OHCA patients, higher mortality was observed in the LT group (60 vs. 28.9%, p
      = 0.018). DISCUSSION AND CONCLUSION: Airway management by LT was not associated
      with higher risk of aspiration. In contrast, higher rates of aspiration and
      pneumonia were observed after ET, especially in OHCA patients. However, a
      possible prognostic impact of supraglottic airway devices remains to be
      elucidated.

PMID- 25850765
TI  - Sugars that Glow in the Dark: Fluorescent Tagged Glucose Bioprobes and their
      Facilitation of the Drug Discovery Process
AB  - Fluorescent tagged glucose probes offer an attractive alternative to traditional,
      radioactive based methods for measuring glucose flux in biological systems. Thus,
      it could be envisaged that these probes would be widely used. However, this is
      not the case and, since their development in the mid-1980s, fluorescent tagged
      glucose bioprobes are relatively underutilized in biological research compared to
      radioactive methods, with only a small number (<10) publications per year using
      these probes. However, within the past five years there has been a surge in
      research activity. By the year 2012, numerous novel probes were developed and the
      number of research publications dramatically increased. This was especially
      relevant for drug discovery applications related to cancer, neurology and
      diabetes research. In this review article, we discuss the research impact of
      these bioprobes and assess which probes have been most successfully applied to
      drug discovery applications. Significantly, we also discuss latest research that
      shows the potential of these probes to be used for drug discovery in animal
      models and their application to in vivo-based drug validation. Overall, we hope
      that this review will raise awareness of the research opportunities that these
      probes offer to the drug discovery research community.

PMID- 25850766
TI  - Exploiting molecular virulence determinants in Burkholderia to develop vaccine
      antigens.
AB  - The Burkholderia genus is a highly diverse group of species that are distributed
      throughout a wide range of environments and habitats. Among this group, which is
      remarkable for its adaptability to a wider range of environmental conditions
      including disinfectants and organic solvents, are a subgroup that represents some
      of the most difficult to treat infections. This subgroup includes Burkholderia
      pseudomallei, the causative agent of melioidosis; B. mallei, the causative agent
      of glanders and B. cepacia complex (Bcc) which causes opportunistic infections in
      people with cystic fibrosis and immunocompromised patients. The latter pathogen
      is itself a group of 18 distinct, but, closely related species. The adaptability
      of this group allows the expression of a rich selection of molecular virulence
      determinants to facilitate its survival in the diverse habitats that it
      colonises. This review will describe a selection of these associated with human
      infection; comparing them across the three pathogens and highlighting their
      potential roles as vaccine candidates. Better integration of the knowledge on the
      pathogenesis and molecular determinants of virulence for these Burkholderia spp
      may allow the development of more efficacious vaccines. 

PMID- 25850767
TI  - Molecular and cellular pathways as treatment targets for biologic therapies in
      systemic sclerosis.
AB  - Recent advances have shed light on the complex pathogenic processes that underlie
      the development and progression of Systemic Sclerosis (SSc) but management of the
      disease remains problematic and curative treatment is not available. Better
      understanding of the underlying pathology has enabled novel therapeutic
      approaches to be investigated, as therapies in rheumatology are becoming
      increasingly disease/ organ-specific, targeting unique biological networks and
      signalling pathways. The pathophysiologic and clinical pleiomorphism of SSc
      however, represents a major barrier to conducting large well-controlled studies
      for the evaluation of non-selective immunosuppressive and novel highly selective
      agents. Therapeutic biologic strategies targeting inflammatory or profibrotic
      cytokines and lymphocyte activation proved to be efficacious in other systemic
      rheumatic diseases but have demonstrated contradictory results in SSc. Blocking
      of tumour necrosis factor alpha and interleukin-6 may improve SSc-associated
      arthritis, while depletion of B-cells may have benefits for skin and lung
      fibrosis, but randomized studies are needed. In this review we critically
      appraise available data for the treatment of SSc focusing on immunologic and
      antifibrotic strategies. Attenuation of the fibrotic process remains an unmet
      goal but the potential to prevent damage by promoting tissue repair has been
      shown in preclinical studies. Translation of these findings into clinical
      practice will hopefully establish new therapeutic options and improve prognosis
      of these patients, for which our therapeutic armamentarium remains poor. 

PMID- 25850768
TI  - Cancer drug discovery targeting histone methyltransferases: an update.
AB  - Epigenetic dysregulation has been recognized as an important contributor to
      cancer initiation and progression as most tumors harbor both genetic and
      epigenetic abnormalities. Inhibiting epigenetic proteins represents a novel
      approach in cancer drug discovery and more profound efficacy and less resistance
      are expected since multiple signaling pathways can be modulated as a result of
      inhibiting a single epigenetic target. Histone methyl transferases (HMTs) are an
      important component in epigenome and HMT inhibitors are being pursued intensely
      by both pharmaceutical industry and academic institutions. In this article we
      will provide an update on the drug discovery effort on several key HMTs. 

PMID- 25850769
TI  - Selection of Potential Pharmacological Targets in ALS Based on Whole- Genome
      Expression Profiling.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal disease caused by the gradual
      degeneration and death of upper and lower motor neurons. Despite continue
      efforts, the etiology and pathogenesis of ALS are not well understood yet. The
      lack of knowledge about molecular and cellular players involved in the
      neurodegenerative progression of ALS hinders effective therapy development.
      Several genomicbased studies have been conducted to identify genetic contributors
      to sporadic ALS (SALS) and new potential pharmacological targets, but these have
      resulted in short and non-overlapping lists of candidates. In the last few years,
      our research group has developed the largest whole-genome expression profile
      database of SALS human samples. We have identified several genes deregulated in
      the motor cortex of SALS patients and analyzed the role of these genes within
      deregulated pathways, providing a full molecular portrait of ALS pathogenesis.
      Some of deregulated genes encode for proteins that are direct or indirect targets
      of experimental or therapeutic drugs already applied to unrelated diseases. In
      this review, we focus on the potential role of candidate targets in ALS
      pathophysiology, highlighting their possible contribution to ALS therapy. The
      rational selection of the most promising drug targets and related modulatory
      drugs may provide a starting point for their preclinical or clinical validation
      and, hopefully, the development of more effective treatments for ALS patients. 

PMID- 25850770
TI  - Tuberculosis: An Inorganic Medicinal Chemistry Perspective.
AB  - Tuberculosis (TB) which is caused by the resilient pathogen Mycobacterium
      tuberculosis (MTB) has re-emerged to become a leading public health problem in
      the world. The growing number of multi-drug resistant MTB strains and the more
      recently emerging problem with the extensively drug resistant strains of the
      pathogen are greatly undermining conventional anti-TB therapeutic strategies
      which are lengthy and expose patients to toxicity and other unwanted side
      effects. The search for new anti-TB drugs essentially involves either the
      repurposing of existing organic drugs which are now off patent and already FDA
      approved, the synthesis of modified analogues of existing organic drugs, with the
      aim of shortening and improving drug treatment for the disease, or the search for
      novel structures that offer the possibility of new mechanisms of action against
      the mycobacterium. Inorganic medicinal chemistry offers an alternative to organic
      drugs through opportunities for the design of therapeutics that target different
      biochemical pathways. The incorporation of metal ions into the molecular
      structure of a potential drug offers the medicinal chemist an opportunity to
      exploit structural diversity, have access to various oxidation states of the
      metal and also offer the possibility of enhancing the activity of an established
      organic drug through its coordination to the metal centre. In this review, we
      summarize what is currently known about the antitubercular capability of metal
      complexes, their mechanisms of action and speculate on their potential
      applications in the clinic. 

PMID- 25850771
TI  - Insights into Ecto-5'-Nucleotidase as a New Target for Cancer Therapy: A
      Medicinal Chemistry Study.
AB  - Ecto-5'-nucleotidase (ecto-5'-NT, 5'-NT, eN, CD73) is a membrane ecto-enzyme that
      is primarily responsible for the extracellular production of adenosine from AMP.
      Ecto-5'-NT is over expressed in various types of cancer cells, leading to
      elevated concentrations of adenosine in the tumor microenvironment. Adenosine has
      also been found to be important in cancer pathogenesis, showing strong
      immunosuppressive effects over antitumor T cells and macrophages and promoting
      neovascularization and cell adherence. These actions support tumor growth and
      development. It has been suggested that the inhibition of ecto-5'-NT results in
      lower extracellular concentrations of adenosine within the tumor
      microenvironment, which would directly affect cancer cells and render malignant
      cells more susceptible to host defense systems. Such mechanisms are proposed to
      represent promising new targets for cancer therapy. The aim of this review is to
      explore the biochemical and structural features of ecto-5'-NT, including a brief
      analysis of its active site by molecular modeling, as a means of evaluating
      whether the inhibition of this enzyme does indeed represent a feasible strategy
      for treating cancer. Known inhibitors and possible prototypes that could be used
      to target ecto-5'-NT during cancer therapy are also discussed.

PMID- 25850772
TI  - Founding of the society for cardiovascular pathology, inc.

PMID- 25850773
TI  - Analysis of formalin-fixed and frozen myocardial autopsy samples for viral genome
      in childhood myocarditis and dilated cardiomyopathy with endocardial
      fibroelastosis using polymerase chain reaction (PCR).
AB  - Viral infection of the myocardium is implicated in the pathogenesis of
      myocarditis and dilated cardiomyopathy (DCM). Enteroviruses have been considered
      the most common viral etiologic agents, based on peripheral culture and serologic
      methods. Recently, polymerase chain reaction (PCR) has been shown to be useful in
      the detection of viral genomes from various infected organs and body fluids. In
      this study, myocardial samples from autopsy specimens (formalin fixed and fresh
      frozen) were examined for enteroviral and DNA viral (adenovirus, herpes simplex
      virus [HSV], and cytomegalovirus (CMV]) genome by PCR. The specimens studied were
      from 58 patients with myocarditis, 28 patients with DCM and endocardial
      fibroelastosis [EFE], and 22 controls. Viral genome was detectable in 34 of the
      58 (59%) autopsy-proven myocarditis samples (18 adenovirus, 12 enterovirus, 2
      CMV, 2 HSV) and 6 of the 28 samples from patients with DCM and EFE (6
      adenovirus). We conclude that PCR is effective in the rapid amplification of
      virus from frozen and formalin-fixed myocardial samples and that adenovirus is an
      important etiologic agent in viral myocarditis as well as DCM with EFE. 

PMID- 25850774
TI  - Acute vascular (humoral) rejection in non-OKT3-treated cardiac transplants.
AB  - To determine the incidence and morphologic features of acute vascular rejection
      (AVR) in cardiac transplant patients who have not received OKT3 induction
      therapy, we performed immunofluorescence (IF) staining for Clq and C3c on 341
      endomyocardial biopsies from 135 patients. Each AVR biopsy, defined by positive
      IF, was further evaluated for C4c, C5, IgG, IgM, and IgA. Light and electron
      microscopy were also performed. The clinical features of each case were reviewed.
      A total of 29 biopsies from 6 recently transplanted patients (1993) and 10
      biopsies from 4 long-term transplants (pre-1993) had IF evidence of AVR. All
      patients with AVR had linear vascular deposits of various complement components
      and immunoglobulins. Of the 6 recently transplanted patients, 4 were multiparous
      females. The male had a single episode of AVR. IF patterns were variable between
      and within patients. Clq and C3c were the most consistently detected complement
      components. IgM was the most frequently detected antibody. Of the 10 cases of
      AVR, 6 occurred within the first month post-transplant. Myocyte necrosis was
      present in all cases with cardiac dysfunction. Patients with early onset AVR had
      more recurrences and one fatality. There was one fatality in the long-term
      transplant group. Concomitant grades 0 to 4+ cellular rejection did not correlate
      with results of IF or clinical severity. The incidence of AVR in non-OKT3-treated
      patients is 7%. Of the early onset patients, 66% are multiparous females,
      indicating the possible importance of prior sensitization. IF patterns are not
      predictive of outcome. AVR may be asymptomatic, but early onset predicts a
      difficult clinical course and is detected only by IF screening. 

PMID- 25850775
TI  - Histological changes in the left and right ventricle in hearts with Ebstein's
      malformation and tricuspid valvar dysplasia: A morphometric study of patients
      dying in the fetal and perinatal periods.
AB  - Both Ebstein's malformation and the related tricuspid valvar dysplasia are often
      associated with tricuspid regurgitation, and impaired right ventricular function
      may develop. Impaired function of the left ventricle in Ebstein's malformation
      has also been described. Interstitial fibrosis has been shown in the right and
      left ventricles of hearts with Ebstein's malformation from neonates, children,
      and adults. The objective of this study was to determine whether interstitial
      fibrosis seen in Ebstein's malformation is an intrinsic part of the congenital
      malformation or is acquired. From the fetal and perinatal periods, we compared 13
      hearts with Ebstein's malformation (6 isolated and 7 with additional
      abnormalities) and 11 with tricuspid valvar dysplasia (3 isolated and 8 with
      additional abnormalities) with 16 controls. Three adult cases of isolated
      Ebstein's malformation in patients aged 17 to 20 years, were compared with 5
      controls. The percentage of interstitial fibrous tissue and the thickness of the
      endocardium in the right and left ventricles were measured using
      histomorphometry. There were similar findings in Ebstein's malformation and
      tricuspid valvar dysplasia. Of 24 fetal and perinatal cases, 23 had normal
      interstitial fibrous tissue. Interstitial fibrosis was found in the right
      ventricle of only 1 perinatal heart with Ebstein's malformation and pulmonary
      stenosis. Of the 9 fetal cases, 4 had minimal right ventricular endocardial
      thickening (up to 10 MUm). The left ventricular endocardium was normal in this
      group. Of the 6 perinatal cases with isolated Ebstein's malformation or tricuspid
      valvar dysplasia, 4 had right and 2 had left ventricular endocardial thickening
      (up to 345 MUm). Of the 3 adult hearts with Ebstein's malformation, 2 had right
      ventricular endocardial thickening (47 and 225 MUm) and 2 had right and 1 had
      left ventricular interstitial fibrosis. These results indicate that in both
      Ebstein's malformation and tricuspid valvar dysplasia the endocardial thickening
      develops in perinatal life, and in Ebstein's malformation the interstitial
      fibrosis develops in later life. 

PMID- 25850776
TI  - Ebstein's malformation-What's in a name?

PMID- 25850777
TI  - Chronic ischemic viable myocardium in man: Aspects of dedifferentiation.
AB  - Histologic analysis of biopsies derived from patients with chronic dysfunctional
      but viable (hibernating) myocardium showed characteristic cell alterations. These
      changes consisted of a partial to complete loss of sarcomeres, accumulation of
      glycogen, and disorganization and loss of sarcoplasmic reticulum. Most of the
      adaptive changes that these affected cells undergo are suggestive of
      dedifferentiation. In the present study the expression and organizational pattern
      of contractile and cytoskeletal proteins such as titin, cardiotin, and alpha
      smooth muscle actin were assessed in hibernating and normal myocardium because
      the expression and organization of these constituents have been related to
      certain stages of cardiomyocyte differentiation. In normal cells titin shows a
      cross-striated staining pattern, whereas cardiotin displays a fibrillar array,
      parallel to the sarcomeres. alpha-Smooth muscle actin is not expressed in adult
      cardiomyocytes. The expression of titin in a punctated pattern and the marked
      decrease to virtual absence of cardiotin in hibernating cardiomyocytes speak in
      favor of an embryonic phenotype of these cells. The re-expression of alpha-smooth
      muscle actin in hibernating cells strongly supports this hypothesis. The
      observations on three different structural proteins of heart muscle suggest that
      hibernating myocardium acquired aspects of muscle cell dedifferentiation. 

PMID- 25850778
TI  - Amyloidosis and endomyocardial biopsy: Correlation of extent and pattern of
      deposition with amyloid immunophenotype in 100 cases.
AB  - The heart is subject to involvement by primary (AL), senile (AS), and familial
      (AF) forms of amyloidosis, but the frequency, severity, and therapy of amyloid
      related cardiac symptoms differ depending on the type of amyloidosis present.
      Endomycardial biopsy is a safe and reliable procedure for diagnosing cardiac
      amyloidosis, and immunohistochemical staining of routinely processed biopsy
      specimens can be performed to classify the type of amyloid present. However,
      whether or not the type can be determined from the histologic extent and pattern
      of amyloid deposition is unclear. Endomyocardial biopsy specimens from 100
      patients with cardiac amyloidosis (74 AL, 22 AS, 4 AF) were examined, and the
      histologic extent and pattern of amyloid deposition were correlated with the
      amyloid immunophenotype. No difference in the extent of amyloid deposition was
      identified among the three types. Interstitial nodules of amyloid were more
      common in AS (82%) than in AL (50%, p = 0.0129), whereas vascular involvement was
      more frequently observed in AL (88%) than in AS (26%, p < 0.0001). Endocardial
      and interstitial pericellular deposition occurred with similar frequencies in
      both groups. Although statistically significant differences existed in the
      patterns of amyloid deposition, they did not allow reliable distinction between
      the different types in individual cases. Consequently, in older patients without
      serum or urinary light chains, immunohistochemical staining is recommended to
      distinguish AL from AS types of amyloid in cardiac biopsy tissues. 

PMID- 25850779
TI  - Eosinophilic myocarditis in patients waiting for heart transplantation.
AB  - We report three patients waiting for heart transplantation who suddenly worsened
      clinically. All three explanted hearts showed a myocarditis with a dense
      eosinophilic infiltrate. Follow-up biopsies and necropsies showed no further
      evidence of cardiac eosinophilic infiltrates. The possible relationship between
      drugs administered before transplantation and clinico-pathological findings is
      discussed. 

PMID- 25850780
TI  - Right ventricular dysplasia: Right and left ventricular involvement
      morphometrically evaluated.
AB  - Right ventricular dysplasia (RVD) is a cardiac anomaly characterized by
      replacement of variable amounts of right ventricular myocardium by adipose
      tissue. This condition is believed to be a selective disorder involving
      extensively the right ventricle, but there are occasional reports of concomitant
      "minor" abnormalities of the left ventricle. The object of this report concerns a
      patient who died after heart transplantation because of an unsuspected RVD of the
      donor heart. We present a morphometric study of the heart in order to evaluate
      the distribution of the fat on both ventricles and to understand the structural
      basis of the heart failure. The results show that a large portion of the right
      ventricle is replaced by fat with a quite homogeneous distribution; the left
      ventricle is also largely replaced by adipose tissue that is primarily localized
      at the apex and decreases from the apex to the basis. The remodeling of the heart
      is attributable to a conspicuous increase in volume of the right ventricle
      associated with a normal number of myocytes that are longer than normal. For
      these reasons, according to Starling's law, the heart develops congestive
      failure. 

PMID- 25850781
TI  - Fibronectin accumulation within cardiac myocytes in rats with elevated plasma
      angiotensin II.
AB  - Elevation in plasma angiotensin II (AngII) is associated with cardiac myocyte
      necrosis. Myocyte necrosis followed by wound healing and fibrosis represents a
      structural remodeling of the myocardium thought to contribute to abnormal
      myocardial function. Fibronectin (FN) is generally considered an early component
      of the healing process that precedes collagen accumulation. To better understand
      the time course of this remodeling process involving both cardiac myocytes and
      extracellular matrix, (i.e., FN and collagen), we used two animal models: (1)
      endogenous activation of the renin-angiotensin system by surgical induction of
      renovascular hypertension and (2) exogenous AngII administration (150 ng/min/kg).
      Animals were killed at different time points within the first two weeks. Both
      "cellular" (cFN) and "plasma" (pFN) FN immunolabeling were compared with collagen
      distribution (picrosirius red stain), together with histopathologic (hematoxylin
      eosin stain) and ultrastructural examination of cardiac myocytes. In each
      experimental group, the pattern and time course of FN immunolabeling was
      coincident with histopathologic evidence of myocyte injury and/or remodeling. We
      found different patterns of FN labeling of cardiac myocytes: (a) homogenous
      intracellular distribution in necrotic myocytes, most obvious on days 1 and 2;
      (b) patchy intracellular distribution in nonnecrotic myocytes starting on day 4;
      and (c) marking internalized capillaries. Both FNs were codistributed throughout
      the myocardium of each ventricle; however, cFN was less pronounced and not seen
      in mature scars. Ultrastructural examination revealed different kinds of
      intramyocytic inclusions, characterized by vacuoles containing
      fibrillar/flocculent material, remnants of unknown origin, or internalized
      capillaries. We conclude that FNs are markers of cardiac myocyte necrosis and
      early interstitial remodeling and that renovascular hypertension and AngII
      administration exhibit the same time course and pattern of FN and collagen
      expression. 

PMID- 25850782
TI  - Ostial stenosis of the left main coronary artery in a young woman 10 years after
      radiation therapy.
AB  - A 26-year-old woman developed critical stenosis of the left main coronary artery
      10 years after radiation treatment for Hodgkins disease. She was operated on but
      died in the immediate postoperative period. At autopsy the pathological findings
      were indistinguishable from those described in "typical" atherosclerotic plaques.

PMID- 25850783
TI  - Making the most of what we have: application of extrapolation approaches in
      radioecological wildlife transfer models.
AB  - We will never have data to populate all of the potential radioecological
      modelling parameters required for wildlife assessments. Therefore, we need robust
      extrapolation approaches which allow us to make best use of our available
      knowledge. This paper reviews and, in some cases, develops, tests and validates
      some of the suggested extrapolation approaches. The concentration ratio
      (CRproduct-diet or CRwo-diet) is shown to be a generic (trans-species) parameter
      which should enable the more abundant data for farm animals to be applied to wild
      species. An allometric model for predicting the biological half-life of
      radionuclides in vertebrates is further tested and generally shown to perform
      acceptably. However, to fully exploit allometry we need to understand why some
      elements do not scale to expected values. For aquatic ecosystems, the
      relationship between log10(a) (a parameter from the allometric relationship for
      the organism-water concentration ratio) and log(Kd) presents a potential
      opportunity to estimate concentration ratios using Kd values. An alternative
      approach to the CRwo-media model proposed for estimating the transfer of
      radionuclides to freshwater fish is used to satisfactorily predict activity
      concentrations in fish of different species from three lakes. We recommend that
      this approach (REML modelling) be further investigated and developed for other
      radionuclides and across a wider range of organisms and ecosystems. Ecological
      stoichiometry shows potential as an extrapolation method in radioecology, either
      from one element to another or from one species to another. Although some of the
      approaches considered require further development and testing, we demonstrate the
      potential to significantly improve predictions of radionuclide transfer to
      wildlife by making better use of available data. 

PMID- 25850784
TI  - Independent and Combined Associations of Physical Activity and Sedentary Behavior
      with Depressive Symptoms Among Japanese Adults.
AB  - BACKGROUND: Associations between levels of sedentary behavior and depressive
      symptoms independently and in combination with different levels of physical
      activity remain unclear. PURPOSE: This study aimed to examine independent and
      combined associations of physical activity (PA) and sedentary behavior (SB) with
      depressive symptoms among Japanese adults. METHOD: An Internet-based survey
      collected data on depression levels (Center for Epidemiologic Studies Depression
      Scale), self-reported time spent in PA and SB (Japanese short version of the
      International Physical Activity Questionnaire), and sociodemographic variables
      from 2,914 adults in 2009. Binary logistic regression analyses were conducted to
      examine the odds ratios (ORs) for being depressed (depression scores >=16)
      according to independent PA levels (none, insufficient, sufficient), SB levels
      (low, moderate, high), and nine combinations of PA and SB categories. RESULTS:
      After adjusting for potential confounders, sufficient PA level was found to be
      related to lower risk of depressive symptoms independently (OR = 0.61), whereas
      no significant associations were observed between SB levels and depression. In
      the combined associations, adults in the sufficient PA/high SB (OR = 0.44),
      sufficient PA/moderate SB (OR = 0.56), and sufficient PA/low SB (OR = 0.57)
      categories were significantly less likely to have depressive symptoms in
      comparison with the no PA/high SB category. CONCLUSION: Meeting physical activity
      recommendations is associated with a lower risk of depressive symptoms,
      regardless of time spent in total sedentary behavior. These results suggest that
      promoting physical activity may be an effective strategy against depressive
      symptoms among Japanese adults.

PMID- 25850786
TI  - [Molecular pathogenesis of thyroid tumors].
AB  - The molecular pathogenesis of thyroid tumors has been an evolving field in the
      past years. The constitutive activation of intracellular tyrosine kinases has
      been identified as a hallmark of thyroid cancer. The activation of MAPK and PI3K
      pathways through somatic gene mutations or gene rearrangements seem to play a
      pivotal role in the pathogenesis of follicular-cell-derived tumors. In poorly
      differentiated tumors and anaplastic tumors often an accumulation of genetic
      alterations from differentiated thyroid cancer but also novel gene mutations can
      be observed. The C-cell-derived medullary thyroid cancer evolves through the
      constitutive activation of the RET kinase, either through germline RET mutations
      or somatic RET and RAS mutations. The better knowledge of the molecular
      pathogenesis allowed the development of targeted therapies in thyroid cancer
      patients. The identification of molecular response markers to tyrosine kinase
      inhibitor therapy is desirable. 

PMID- 25850789
TI  - The human hookworm vaccine: recent updates and prospects for success.
AB  - Approximately 440 million people globally are afflicted by hookworm disease, one
      of the 17 WHO-recognized neglected tropical diseases (NTDs). The iron-deficiency
      anaemia attributed to this disease contributes to at least 3.2 million disability
      adjusted life years (DALYs) according to the Global Burden of Disease Study 2010.
      The current WHO-recommended control strategies rely primarily on mass drug
      administration or preventive chemotherapy. However, evidence is starting to
      accumulate confirming that preventive chemotherapy alone will not be sufficient
      to reduce the reinfection rates of hookworm, especially in areas of heavy
      transmission. The global health and research community is currently building a
      consensus stressing the need for the advancement of research and innovation to
      bridge the gaps and identify new public health interventions for diseases such as
      hookworm and other NTDs. This paper presents the strategies used by the Sabin
      Vaccine Institute Product Development Partnership (Sabin PDP) in their ongoing
      endeavour for the development of a human hookworm vaccine. Recent updates and the
      current prospects for success of an effective human hookworm vaccine, as a new
      technology to be linked to or combined with drug interventions, are presented. 

PMID- 25850787
TI  - SIRT1 and Neural Cell Fate Determination.
AB  - During the development of the central nervous system (CNS), neurons and glia are
      derived from multipotent neural stem cells (NSCs) undergoing self-renewal. NSC
      commitment and differentiation are tightly controlled by intrinsic and external
      regulatory mechanisms in space- and time-related fashions. SIRT1, a silent
      information regulator 2 (Sir2) ortholog, is expressed in several areas of the
      brain and has been reported to be involved in the self-renewal, multipotency, and
      fate determination of NSCs. Recent studies have highlighted the role of the
      deacetylase activity of SIRT1 in the determination of the final fate of NSCs.
      This review summarizes the roles of SIRT1 in the expansion and differentiation of
      NSCs, specification of neuronal subtypes and glial cells, and reprogramming of
      functional neurons from embryonic stem cells and fibroblasts. This review also
      discusses potential signaling pathways through which SIRT1 can exhibit versatile
      functions in NSCs to regulate the cell fate decisions of neurons and glia.

PMID- 25850788
TI  - Mammalian adaptation of influenza A(H7N9) virus is limited by a narrow genetic
      bottleneck.
AB  - Human infection with avian influenza A(H7N9) virus is associated mainly with the
      exposure to infected poultry. The factors that allow interspecies transmission
      but limit human-to-human transmission are unknown. Here we show that
      A/Anhui/1/2013(H7N9) influenza virus infection of chickens (natural hosts) is
      asymptomatic and that it generates a high genetic diversity. In contrast,
      diversity is tightly restricted in infected ferrets, limiting further adaptation
      to a fully transmissible form. Airborne transmission in ferrets is accompanied by
      the mutations in PB1, NP and NA genes that reduce viral polymerase and
      neuraminidase activity. Therefore, while A(H7N9) virus can infect mammals,
      further adaptation appears to incur a fitness cost. Our results reveal that a
      tight genetic bottleneck during avian-to-mammalian transmission is a limiting
      factor in A(H7N9) influenza virus adaptation to mammals. This previously
      unrecognized biological mechanism limiting species jumps provides a measure of
      adaptive potential and may serve as a risk assessment tool for pandemic
      preparedness. 

PMID- 25850790
TI  - Stone formation and management after bariatric surgery.
AB  - Obesity is a significant health concern and is associated with an increased risk
      of nephrolithiasis, particularly in women. The underlying pathophysiology of
      stone formation in obese patients is thought to be related to insulin resistance,
      dietary factors, and a lithogenic urinary profile. Uric acid stones and calcium
      oxalate stones are common in these patients. Use of surgical procedures for
      obesity (bariatric surgery) has risen over the past two decades. Although such
      procedures effectively manage obesity-dependent comorbidities, several large,
      controlled studies have revealed that modern bariatric surgeries increase the
      risk of nephrolithiasis by approximately twofold. In patients who have undergone
      bariatric surgery, fat malabsorption leads to hyperabsorption of oxalate, which
      is exacerbated by an increased permeability of the gut to oxalate. Patients who
      have undergone bariatric surgery show characteristic 24 h urine parameters
      including low urine volume, low urinary pH, hypocitraturia, hyperoxaluria and
      hyperuricosuria. Prevention of stones with dietary limitation of oxalate and
      sodium and a high intake of fluids is critical, and calcium supplementation with
      calcium citrate is typically required. Potassium citrate is valuable for treating
      the common metabolic derangements as it raises urinary pH, enhances the activity
      of stone inhibitors, reduces the supersaturation of calcium oxalate, and corrects
      hypokalaemia. Both pyridoxine and probiotics have been shown in small studies to
      reduce hyperoxaluria, but further study is necessary to clarify their effects on
      stone morbidity in the bariatric surgery population. 

PMID- 25850791
TI  - Prostate cancer: New gene panel for aggressive prostate cancer.

PMID- 25850793
TI  - Therapy: Are long-acting intramuscular testosterone injections safe?

PMID- 25850792
TI  - Current understanding of hypospadias: relevance of animal models.
AB  - Hypospadias is a congenital abnormality of the penile urethra with an incidence
      of approximately 1:200-1:300 male births, which has doubled over the past three
      decades. The aetiology of the overwhelming majority of hypospadias remains
      unknown but appears to be a combination of genetic susceptibility and prenatal
      exposure to endocrine disruptors. Reliable animal models of hypospadias are
      required for better understanding of the mechanisms of normal penile urethral
      formation and hence hypospadias. Mice and/or rats are generally used for
      experimental modelling of hypospadias, however these do not fully reflect the
      human condition. To use these models successfully, researchers must understand
      the similarities and differences between mouse, rat and human penile anatomy as
      well as the normal morphogenetic mechanisms of penile development in these
      species. Despite some important differences, numerous features of animal and
      human hypospadias are shared: the prevalence of distal penile malformations;
      disruption of the urethral meatus; disruption of urethra-associated erectile
      bodies; and a common mechanism of impaired epithelial fusion events. Rat and
      mouse models of hypospadias are crucial to our understanding of hypospadias to
      ultimately reduce its incidence through better preventive strategies. 

PMID- 25850794
TI  - Sexual dysfunction: Anandamide shows promise for lifelong delayed ejaculation.

PMID- 25850796
TI  - Sexual dysfunction: Blue light, not blue pills, for erectile dysfunction.

PMID- 25850797
TI  - Prostate cancer: New biomarker panel prognosticates patient survival.

PMID- 25850798
TI  - Urinary incontinence: Propagating contractions influence urinary bladder tone.

PMID- 25850799
TI  - Microengineered peripheral nerve-on-a-chip for preclinical physiological testing.
AB  - The use of advanced in vitro testing is a powerful tool to develop predictive
      cellular assays suitable for improving the high attrition rates of novel
      pharmaceutical compounds. A microscale, organotypic model of nerve tissue with
      physiological measures that mimic clinical nerve compound action potential (CAP)
      and nerve fiber density (NFD) tests may be more predictive of clinical outcomes,
      enabling a more cost-effective approach for selecting promising lead compounds
      with higher chances of late-stage success. However, the neurological
      architecture, physiology, and surrounding extracellular matrix are hard to mimic
      in vitro. Using a dual hydrogel construct and explants from rat embryonic dorsal
      root ganglia, the present study describes an in vitro method for
      electrophysiological recording of intra- and extra-cellular recordings using a
      spatially-controlled, microengineered sensory neural fiber tract. Specifically,
      these 3D neural cultures exhibit both structural and functional characteristics
      that closely mimic those of afferent sensory peripheral fibers found in vivo. Our
      dual hydrogel system spatially confines growth to geometries resembling nerve
      fiber tracts, allowing for a high density of parallel, fasciculated neural
      growth. Perhaps more importantly, outputs resembling clinically relevant test
      criteria, including the measurement of CAP and NFD are possible through our
      advanced model. Moreover, the 3D hydrogel constructs allow flexibility in
      incorporated cell type, geometric fabrication, and electrical manipulation,
      providing a viable assay for systematic culture, perturbation, and testing of
      biomimetic neural growth for mechanistic studies necessitating physiologically
      relevant readouts. 

PMID- 25850805
TI  - Liposomes as novel anti-infectives targeting bacterial virulence factors?
AB  - A recent report commissioned by Prime Minister David Cameron and chaired by
      former Goldman Sachs chief economist Jim O'Neill warns that the emergence,
      persistence and spread of antimicrobial resistance could lead to 10 million
      deaths per year and cause an economic burden as much as US$100 trillion by 2050.
      In the midst of this global crisis, unprecedented paths are being explored to
      combat bacterial infection. Virulence factors, and more particularly pore-forming
      toxins, play a key role in increasing morbidity and mortality caused by drug
      resistant bacterial infections. Novel anti-infective liposomes specifically
      targeting and neutralizing these cytotoxic toxins are potential game-changers in
      the fight against deadly infections. 

PMID- 25850800
TI  - Flexibility decline contributes to similarity of past and future thinking in
      Alzheimer's disease.
AB  - A striking similarity has been suggested between past and future thinking in
      Alzheimer's Disease (AD), a similarity attributable to abnormalities in common
      modular cognitive functions and neuroanatomical substrates. This study extends
      this literature by identifying specific executive function deficits underlying
      past and future thinking in AD. Twenty-four participants with a clinical
      diagnosis of probable (mild) AD and 26 older controls generated past and future
      events and underwent tests of binding and the executive functions of flexibility,
      inhibition, and updating. AD patients showed similar autobiographical
      performances in past and future event generation, and so did control
      participants. In each group, the similarity of past and future thinking was
      predicted by flexibility. Furthermore, AD patients with low flexibility showed
      higher similarity of past and future thinking than those with high flexibility.
      These findings are interpreted in terms of involvement of the hippocampus and
      frontal lobes in future thinking. Deficits in these brain regions in AD are
      likely to compromise the ability to recombine episodic information into novel and
      flexible configurations as scenarios for the future.

PMID- 25850806
TI  - Community-acquired Acinetobacter baumannii: clinical characteristics,
      epidemiology and pathogenesis.
AB  - Community-acquired Acinetobacter baumannii (CA-Ab) is a rare but serious cause of
      community-acquired pneumonia in tropical regions of the world. CA-Ab infections
      predominantly affect individuals with risk factors, which include excess alcohol
      consumption, diabetes mellitus, smoking and chronic lung disease. CA-Ab pneumonia
      presents as a surprisingly fulminant course and is characterized by a rapid onset
      of fever, severe respiratory symptoms and multi-organ dysfunction, with a
      mortality rate reported as high as 64%. It is unclear whether the distinct
      clinical syndrome caused by CA-Ab is because of host predisposing factors or
      unique bacterial characteristics, or a combination of both. Deepening our
      understanding of the drivers of overwhelming CA-Ab infection will provide
      important insights into preventative and therapeutic strategies. 

PMID- 25850807
TI  - Electron transfer budgets and kinetics of abiotic oxidation and incorporation of
      aqueous sulfide by dissolved organic matter.
AB  - The reactivity of natural dissolved organic matter toward sulfide and has not
      been well studied with regard to electron transfer, product formation, and
      kinetics. We thus investigated the abiotic transformation of sulfide upon
      reaction with reduced and nonreduced Sigma-Aldrich humic acid (HA), at pH 6 under
      anoxic conditions. Sulfide reacted with nonreduced HA at conditional rate
      constants of 0.227-0.325 h(-1). The main transformation products were elemental S
      (S0) and thiosulfate (S2O3(2-)), yielding electron accepting capacities of 2.82
      1.75 MUmol e- (mg C)(-1). Native iron contents in the HA could account for only 6
      9% of this electron transfer. About 22-37% of S reacted with the HA to form
      organic S (Sorg). Formation of Sorg was observed and no inorganic transformation
      products occurred for reduced HA. X-ray absorption near edge structure
      spectroscopy supported Sorg to be mainly zerovalent, such as thiols, organic di-
      and polysulfides, or heterocycles. In conclusion, our results demonstrate that HA
      can abiotically reoxidize sulfide in anoxic environments at rates competitive to
      sulfide oxidation by molecular oxygen or iron oxides.

PMID- 25850809
TI  - Low-Temperature Cathodoluminescence Investigations of High-Quality Zinc Oxide
      Nanorods.
AB  - We present results of cathodoluminescence (CL) investigations of high-quality
      zinc oxide (ZnO) nanorods obtained by an extremely fast hydrothermal method on a
      silicon substrate. A scanning electron microscopy (SEM) system equipped with CL
      allows direct comparison of SEM images and CL maps, taken from exactly the same
      areas of samples. Investigations are performed at a temperature of 5 K. An
      interlink between sample microstructure and emission properties is investigated.
      CL confirms a very high quality of ZnO nanorods produced by our method. In
      addition, the presence of super radiation effects in ZnO nanorod arrays is
      suggested. 

PMID- 25850808
TI  - Rice FLAVIN-BINDING, KELCH REPEAT, F-BOX 1 (OsFKF1) promotes flowering
      independent of photoperiod.
AB  - In the facultative long-day (LD) plant Arabidopsis thaliana, FLAVIN-BINDING,
      KELCH REPEAT, F-BOX 1 (FKF1) is activated by blue light and promotes flowering
      through the transcriptional and post-translational regulation of CONSTANS under
      inductive LD conditions. By contrast, the facultative short day (SD) plant rice
      (Oryza sativa) flowers early under inductive SD and late under non-inductive LD
      conditions; the regulatory function of OsFKF1 remains elusive. Here we show that
      osfkf1 mutants flower late under SD, LD and natural LD conditions.
      Transcriptional analysis revealed that OsFKF1 up-regulates the expression of the
      floral activator Ehd2 and down-regulates the expression of the floral repressor
      Ghd7; these regulators up- and down-regulate Ehd1 expression, respectively.
      Moreover, OsFKF1 can up-regulate Ehd1 expression under blue light treatment,
      without affecting the expression of Ehd2 and Ghd7. In contrast to the LD-specific
      floral activator Arabidopsis FKF1, OsFKF1 likely acts as an autonomous floral
      activator because it promotes flowering independent of photoperiod, probably via
      its distinct roles in controlling the expression of rice-specific genes including
      Ehd2, Ghd7 and Ehd1. Like Arabidopsis FKF1, which interacts with GI and CDF1,
      OsFKF1 also interacts with OsGI and OsCDF1 (also termed OsDOF12). Thus, we have
      identified similar and distinct roles of FKF1 in Arabidopsis and rice. 

PMID- 25850811
TI  - A survey of nitrate and nitrite concentrations in conventional and organic
      labeled raw vegetables at retail.
AB  - A national survey of the nitrate ( NO3(-)) and nitrite ( NO2(-)) concentrations
      in raw and highly consumed vegetables available at retail in the United States
      was conducted. A total of 194 samples of fresh broccoli, cabbage, celery,
      lettuce, and spinach categorized as conventional or organic by label were
      collected from 5 major cities in different geographic regions of the United
      States and analyzed to determine NO3(-) and NO2(-) concentrations. There were no
      differences in the mean NO2(-) values of conventional compared with organic
      vegetables taken from the 5 metropolitan areas. However, significant differences
      in mean pairwise comparisons between some conventional and organic vegetables for
      NO3(-) content were observed. The mean NO2(-) concentration of both conventional
      and organic vegetables ranged between 0.1 and 1.2 mg/kg of fresh weight (FW) with
      the exception of conventional spinach that contained 8.0 mg/kg FW. Mean NO3(-)
      contents of conventional broccoli, cabbage, celery, lettuce, and spinach were
      394, 418, 1496, 851, and 2797 mg/kg FW, respectively, while their organic-labeled
      counterparts averaged 204, 552, 912, 844, and 1318 mg/kg FW. In most cases,
      organic vegetables were numerically lower in NO3(-) content than their
      conventional counterparts. Based on survey results, the finding that low NO3(-)
      levels were observed in some organic vegetables in different cities may warrant
      further study to determine if true differences exist, due to production
      practices, seasonal differences, and the magnitudes of those differences.
      Furthermore, the geographic differences in NO3(-) content of vegetables may flaw
      estimates of daily NO2(-) and NO3(-) exposure.

PMID- 25850812
TI  - Characterization of the 1,1-HF Elimination Reaction from the Competition between
      the 1,1-HF and 1,2-DF Unimolecular Elimination Reactions of CD3CD2CHF2.
AB  - The recombination of CHF2 and C2D5 radicals was used to produce CD3CD2CHF2*
      molecules with 96 kcal mol(-1) of vibrational energy in a room temperature bath
      gas. The formation of CD3CD?CHF and CD3CD?CDF was used to identify the 1,2-DF and
      1,1-HF unimolecular elimination channels; CD3CD?CDF is formed by isomerization of
      the singlet-state CD3CD2CF carbene. The total unimolecular rate constant is 1.6 *
      10(6) s(-1), and the branching ratio for 1,1-HF elimination is 0.25. Threshold
      energies of 64 +/- 2 and 73 +/- 2 kcal mol(-1) were assigned to the 1,2-DF and
      1,1-HF reaction channels. The E and Z isomers of 1-fluoropropene were observed
      for each reaction; approximately 30% of the CD3CD?CDF molecules derived from 1,1
      HF elimination retained enough energy to undergo cis-trans isomerization.
      Electronic structure calculations with density-functional theory were used to
      characterize the transition-state structures and the H atom migration barrier for
      CD3CD2CF. Adjustment of the rate constants to account for kinetic-isotope effects
      suggest that the branching ratio would be 0.20 for 1,1-HF elimination from
      C2H5CHF2. The results from an earlier study of CD3CHF2 and CH3CHF2 are also
      reinterpreted to assign a threshold energy of 74 kcal mol(-1) for the 1,1-HF
      elimination reaction. Because CHF2CHF2* is generated in the photolysis system,
      the 1,1-and 1,2-HF-elimination reactions of CHF2CHF2* are discussed. The 1,1-HF
      channel was identified by trapping the CF2HCF carbene with cis-butene-2. 

PMID- 25850810
TI  - Human B-cell and progenitor stages as determined by probability state modeling of
      multidimensional cytometry data.
AB  - BACKGROUND: Human progenitor and B-cell development is a highly regulated process
      characterized by the ordered differential expression of numerous cell-surface and
      intracytoplasmic antigens. This study investigates the underlying coordination of
      these modulations by examining a series of normal bone marrow samples with the
      method of probability state modeling or PSM. RESULTS: The study is divided into
      two sections. The first section examines B-cell stages subsequent to CD19 up
      regulation. The second section assesses an earlier differentiation stage before
      and including CD19 up-regulation. POST-CD19 ANTIGENIC UP-REGULATION: Statistical
      analyses of cytometry data derived from sixteen normal bone marrow specimens
      revealed that B cells have at least three distinct coordinated changes, forming
      four stages labeled as B1, B2, B3, and B4. At the end of B1; CD34 antigen
      expression down-regulates with TdT while CD45, CD81, and CD20 slightly up
      regulate. At the end of B2, CD45 and CD20 up-regulate. At the end of B3 and
      beginning of B4; CD10, CD38, and CD81 down-regulate while CD22 and CD44 up
      regulate. PRE-CD19 ANTIGENIC UP-REGULATION: Statistical analysis of ten normal
      bone marrows revealed that there are at least two measurable coordinated changes
      with progenitors, forming three stages labeled as P1, P2, and P3. At the end of
      P1, CD38 up-regulates. At the end of P2; CD19, CD10, CD81, CD22, and CD9 up
      regulate while CD44 down-regulates slightly. CONCLUSIONS: These objective results
      yield a clearer immunophenotypic picture of the underlying cellular mechanisms
      that are operating in these important developmental processes. Also,
      unambiguously determined stages define what is meant by "normal" B-cell
      development and may serve as a preliminary step for the development of highly
      sensitive minimum residual disease detection systems. A companion article is
      simultaneously being published in Cytometry Part A that will explain in further
      detail the theory behind PSM. Three short relevant videos are available in the
      online supporting information for both of these papers.

PMID- 25850813
TI  - ASXL1 mutations are frequent and prognostically detrimental in CSF3R-mutated
      chronic neutrophilic leukemia.
AB  - Colony stimulating factor 3 receptor gene (CSF3R) mutations have recently been
      associated with chronic neutrophilic leukemia (CNL). Fourteen patients with CSF3R
      mutated CNL (median age 67 years; 57% males) were screened for additional
      mutations; 8 (57%) and 5 (38%) harbored an ASXL1 and/or SETBP1 mutation (two
      patients expressed both), respectively. Two patients developed blastic
      transformation, both SETBP1-mutated and ASXL1-unmutated, whereas two other cases
      evolved into chronic myelomonocytic leukemia (CMML), both ASXL1-mutated and
      SETBP1-unmutated. Median survival was 23.2 months (10 deaths documented). On
      multivariable analysis mutated ASXL1 (P = 0.009; HR 19.6, 95% CI 2.1-184.1) and
      thrombocytopenia (P = 0.005; HR 28.8, 95% CI 2.8-298.2) were independently
      predictive of shortened survival. This study provides information on the natural
      history of CSF3R-mutated CNL and identifies mutant ASXL1 and thrombocytopenia as
      risk factors for survival. The study also suggests pathogenetic roles for SETBP1
      and ASXL1 mutations in disease evolution into blast phase disease and CMML,
      respectively.

PMID- 25850814
TI  - A double-blind randomised controlled trial testing the effect of a barley product
      containing varying amounts and types of fibre on the postprandial glucose
      response of healthy volunteers.
AB  - The aim of the present study was to determine if the consumption of barley
      tortillas varying in fibre and/or starch composition affected postprandial
      glucose, insulin, glucagon-like peptide-1 (GLP-1) or peptide YY concentrations. A
      double-blind, randomised, controlled trial was performed with twelve healthy
      adults. They each consumed one of five barley tortillas or a glucose drink on six
      individual visits separated by at least 1 week. Tortillas were made from 100%
      barley flour blends using five different milling fractions to achieve the desired
      compositions. All treatments provided 50 g of available carbohydrate and were
      designed to make the following comparisons: (1) low-starch amylose (0%) v. high
      starch amylose (42%) with similar beta-glucan and insoluble fibre content; (2)
      low beta-glucan (4.5 g) v. medium beta-glucan (7.8 g) v. high beta-glucan (11.6
      g) with similar starch amylose and insoluble fibre content; and (3) low insoluble
      fibre (7.4 g) v. high insoluble fibre (19.6 g) with similar starch amylose and
      beta-glucan content. Blood was collected at fasting and at multiple intervals
      until 180 min after the first bite/sip of the test product. Amylose and insoluble
      fibre content did not alter postprandial glucose and insulin, but high-beta
      glucan tortillas elicited a lower glucose and insulin response as compared to the
      low-beta-glucan tortillas. The tortillas with high insoluble fibre had a higher
      AUC for GLP-1 as compared to the tortillas with low insoluble fibre, whereas
      amylose and beta-glucan content had no effect. Results show that processing
      methods can be used to optimise barley foods to reduce postprandial blood glucose
      responses and factors that may influence satiety.

PMID- 25850815
TI  - Controlling the capture and release of DNA with a dual-responsive cationic
      surfactant.
AB  - A dual-responsive cationic surfactant, 4-ethoxy-4'-(trimethyl- aminoethoxy)
      azobenzene trichloromonobromoferrate (azoTAFe), which contains both a light
      responsive moiety azobenzene and a paramagnetic counterion, [FeCl3Br](-), was
      designed and synthesized. Not only does this cationic surfactant abundantly
      utilize inexhaustible and clean sources, i.e., light and magnetic field, but it
      also serves as a powerful dual-switch molecule for effectively controlling the
      capture and release of DNA. Our results could provide potential applications in
      gene therapy for creating smart and versatile machines to control the transport
      and delivery of DNA more intelligently and robustly. It was proved that the light
      switch can independently realize a reversible DNA compaction. The introduction of
      a magnetic switch can significantly enhance the compaction efficiency, help
      compact DNA with a lower dosage and achieve a magnetic field-based targeted
      transport of DNA. In addition, the light switch can make up the irreversibility
      of magnetic switch. This kind of self-complementation makes the cationic azoTAFe
      be useful as a potential tool that can be applied to the field of gene therapy
      and nanomedicine. 

PMID- 25850816
TI  - Ex Vivo Induced Regulatory Human/Murine Mesenchymal Stem Cells as Immune
      Modulators.
AB  - Over the past decade there has been a growing interest in using mesenchymal stem
      cells (MSCs) as an immune-regulatory agent for prevention and treatment of
      various immune disorders including graft-versus-host disease (GVHD), transplanted
      organ rejection, and autoimmune diseases. However, the high diversity in the
      results from clinical trials using MSCs for such disorders emphasizes the need
      for MSCs to be "professionalized" ex vivo to a more defined regulatory phenotype
      before administering to patients. To this aim, we have established an ex vivo
      immunomodulatory triple combination treatment (TCT) for MSCs, using IFNgamma,
      TGFbeta, and kynurenine. We show that pretreated MSCs acquire an immunomodulatory
      phenotype, have improved regulatory functions, and upregulate the expression of
      inducible nitric oxide synthase, indoleamine 2,3-dioxygenase, cyclooxygenase-2
      (COX2), heme oxygenase 1, leukemia inhibitory factor (LIF), and programmed death
      ligand 1. We define the pathway of kynurenine induced aryl hydrocarbon receptor
      activation in MSCs and how it contributes to the upregulation of COX2 expression
      and IL-6 downregulation. The combination of reduced IL-6 secretion with enhanced
      LIF expression leads to the inhibition of Th17 differentiation in coculture of
      TCT MSCs and lymphocytes. To test the immunomodulatory function of TCT MSCs in
      vivo, we used the cells as GVHD prophylaxis in a GVHD mouse model. TCT MSCs
      administration significantly decreased GVHD score and improved mouse survival.
      Importantly, single administration could attenuate disease symptoms for more than
      3 weeks. Based on these results, we suggest considering TCT MSCs as an improved
      cell therapy for systemic diseases with an underlying inflammatory and
      immunologic etiology. Stem Cells 2015;33:2256-2267. 

PMID- 25850817
TI  - Incidence of intravascular injection and the spread of contrast media during S1
      transforaminal epidural steroid injection by two approaches: anteroposterior vs
      oblique.
AB  - The aim of this randomised study was to compare the incidence of intravascular
      injections during S1 transforaminal epidural steroid injection performed in the
      anteroposterior and oblique views. We also compared epidural spread patterns of
      contrast media, which included 201 injections at the S1 level. The overall
      incidence of intravascular injection during S1 transforaminal epidural steroid
      injection in the anteroposterior view was 29% (29/99), significantly higher than
      in the oblique view (11%, 11/102, p = 0.001). There were no significant
      differences between the two groups for epidural spread of contrast media in cases
      where intravascular injections did not occur (p = 0.77). Performing S1
      transforaminal epidural steroid injection in the oblique view rather than the
      anteroposterior view reduces the risk of intravascular injections.

PMID- 25850818
TI  - COMPARISON OF CHITIN STRUCTURES DERIVED FROM THREE COMMON WASP SPECIES (Vespa
      crabro LINNAEUS, 1758, Vespa orientalis LINNAEUS, 1771 and Vespula germanica
      (FABRICIUS, 1793)).
AB  - There has been no study on the chitin structure of wasp species. Here, we
      selected the three most common wasp species belonging to the family Vespidae for
      chitin extraction and characterization. Chitin was isolated from each wasp
      species and characterized by Fourier transform infrared spectroscopy (FTIR),
      thermogravimetric analysis (TGA), X-ray diffractometry (XRD), elemental analysis
      (EA), and scanning electron microscopy (SEM). The chitin contents of Vespa
      crabro, Vespa orientalis, and Vespula germanica were 8.3, 6.4, and 11.9%,
      respectively. The crystalline index (CrI) values for the chitin extracted from
      each species were 69.88, 53.92, and 50%, respectively. The most important finding
      of the study is that although the same method was used to extract chitin from
      each of the three wasp species, the degree of acetylation was different: for V.
      crabro and V. orientalis it was 96.85 and 99.82% (the chitin was extremely pure),
      respectively, whereas that for V. germanica the chitin was 79.83%. 

PMID- 25850819
TI  - Nonsuicidal self-injury and affect regulation: recent findings from experimental
      and ecological momentary assessment studies and future directions.
AB  - CONTEXT: Although research indicates that nonsuicidal self-injury (NSSI) may be
      used as a form of emotion regulation, studies have largely relied on the use of
      retrospective self-report data, which limits inferences about directionality of
      effects. Recently, researchers have started to employ lab-based experimental
      (e.g., guided imagery, acute pain) and moment sampling approaches to the study of
      NSSI. METHODS: In the present study, we conducted a review of this recent
      literature, using several electronic databases (e.g., PsychINFO, ERIC, CINAHL).
      RESULTS: We identified 18 studies that met our inclusion criteria. Findings
      indicated that the administration of pain was associated with decreases in
      negative affect among both self-injurers and noninjurers, although these declines
      were more pronounced for self-injurers in some studies. CONCLUSIONS: We discuss
      findings within the context of two central theories (i.e., opponent-process
      theory and distraction theory) and offer several recommendations for future
      research in this area.

PMID- 25850820
TI  - Ischemia and reperfusion related myocardial inflammation: A network of cells and
      mediators targeting the cardiomyocyte.
AB  - Occlusion of a coronary artery if maintained for longer period of time results in
      damage of the cardiac tissue. However, restoration of blood flow to previously
      ischemic tissue can itself induce further cardiac damage, a phenomenon known as
      myocardial reperfusion injury. Cardiac homoeostasis is supported by a network of
      direct and indirect interactions between cardiomyocytes and resident cell types
      such as fibroblasts, adipocytes, and endothelial cells or invading blood cells.
      This review will discuss the role of the cellular interplay in ischemia
      reperfusion injury from a cardiomyocyte-centered view, although we are aware that
      other cellular interactions are equally important. We will try to work out
      currently unresolved questions and potential future directions in the field.

PMID- 25850823
TI  - Development of full-thickness human skin equivalents with blood and lymph-like
      capillary networks by cell coating technology.
AB  - We developed a human skin equivalent (HSE) containing blood and lymph-like
      capillary networks using a cell coating technique, which is a rapid fabrication
      technology of three-dimensional cellular constructs by cell surface coating using
      layer-by-layer assembled nanofilms of extracellular matrices. The thickness of
      dermis consisting of normal human dermal fibroblasts was easily controlled from
      approximately 5 to 100 um by altering the seeded cell number. Keratinocytes as a
      major cell population showed homogeneous differentiation on the surface of the
      dermis by lifting to air-liquid interface. Histological analysis revealed four
      distinct layers such as basal layer, spinous layer, granular layer, and cornified
      cell layer in the epidermis. Interestingly, the measurement of transepithelial
      electrical resistance (TEER) indicated prolongation of the attainment time for
      maximum value by increasing the number of the dermal fibroblasts, and the HSEs
      with six layers of dermis revealed the longest period maintaining over 500 Omega
      cm(2) of TEER. The co-sandwich culture of human umbilical vein endothelial cells
      and normal human dermal lymphatic microvascular endothelial cells within eight
      layered dermis showed in vitro co-network formation of individual blood and lymph
      like capillaries inside the dermis. This is the report for homogeneous full
      thickness HSEs with blood and lymph capillary networks, which will be useful for
      biomedical and pharmaceutical applications.

PMID- 25850822
TI  - Online monitoring of fermentation processes via non-invasive low-field NMR.
AB  - For the development of biotechnological processes in academia as well as in
      industry new techniques are required which enable online monitoring for process
      characterization and control. Nuclear magnetic resonance (NMR) spectroscopy is a
      promising analytical tool, which has already found broad applications in offline
      process analysis. The use of online monitoring, however, is oftentimes
      constrained by high complexity of custom-made NMR bioreactors and considerable
      costs for high-field NMR instruments (>US$200,000). Therefore, low-field (1) H
      NMR was investigated in this study in a bypass system for real-time observation
      of fermentation processes. The new technique was validated with two microbial
      systems. For the yeast Hansenula polymorpha glycerol consumption could accurately
      be assessed in spite of the presence of high amounts of complex constituents in
      the medium. During cultivation of the fungal strain Ustilago maydis, which is
      accompanied by the formation of several by-products, the concentrations of
      glucose, itaconic acid, and the relative amount of glycolipids could be
      quantified. While low-field spectra are characterized by reduced spectral
      resolution compared to high-field NMR, the compact design combined with the high
      temporal resolution (15 s-8 min) of spectra acquisition allowed online monitoring
      of the respective processes. Both applications clearly demonstrate that the
      investigated technique is well suited for reaction monitoring in opaque media
      while at the same time it is highly robust and chemically specific. It can thus
      be concluded that low-field NMR spectroscopy has a great potential for non
      invasive online monitoring of biotechnological processes at the research and
      practical industrial scales.

PMID- 25850824
TI  - VARIABILITY IN THE ULTRASONOGRAPHIC APPEARANCE OF THE PANCREAS IN HEALTHY DOGS
      COMPARED TO DOGS WITH HYPERADRENOCORTICISM.
AB  - Anecdotally, an unusually hyperechoic pancreas can be found in seemingly healthy
      dogs on ultrasound examination and the prevalence and clinical significance of
      this finding is unknown. The objective of this study was to describe the
      prevalence of a hyperechoic and/or heterogenous pancreas in healthy dogs and
      correlate these findings to weight, age, and body condition score (BCS). An
      additional objective was to describe the prevalence of a hyperechoic and/or
      heterogenous pancreas in dogs with hyperadrenocorticism and compare this to the
      healthy dogs. Pancreata of 74 healthy dogs were evaluated prospectively and
      pancreatic echogenicity and echotexture were graded. Each dog's age, BCS, and
      weight were recorded. Dogs were screened for health by physical examination,
      serum chemistry panel, urine specific gravity, and a canine pancreatic lipase
      immunoreactivity assay. Pancreatic images for 92 dogs having hyperadrenocorticism
      were also reviewed and pancreatic echogenicity and echotexture were recorded. The
      prevalence of pancreatic hyperechogenicity in normal dogs was 7% (5 of 74) and
      heterogeneity was 40% (30 of 74). No correlation existed between pancreatic
      echogenicity and weight, age, or BCS (P > 0.1 for all sets). A statistically
      significant increase in the proportion of dogs having a hyperechoic pancreas was
      found in the hyperadrenocorticism sample of dogs (40%, 37 of 92, P < 0.0001). The
      underlying cause of pancreatic variability in the few healthy dogs and in dogs
      with hyperadrenocorticism is unknown and the varying appearance of the pancreas
      in these samples confounds interpretation of diseases such as chronic
      pancreatitis. 

PMID- 25850821
TI  - Toward a Cancer Drug of Fungal Origin.
AB  - Although fungi produce highly structurally diverse metabolites, many of which
      have served as excellent sources of pharmaceuticals, no fungi-derived agent has
      been approved as a cancer drug so far. This is despite a tremendous amount of
      research being aimed at the identification of fungal metabolites with promising
      anticancer activities. This review discusses the results of clinical testing of
      fungal metabolites and their synthetic derivatives, with the goal to evaluate how
      far we are from an approved cancer drug of fungal origin. Also, because in vivo
      studies in animal models are predictive of the efficacy and toxicity of a given
      compound in a clinical situation, literature describing animal cancer testing of
      compounds of fungal origin is reviewed as well. Agents showing the potential to
      advance to clinical trials are also identified. Finally, the technological
      challenges involved in the exploitation of fungal biodiversity and procurement of
      sufficient quantities of clinical candidates are discussed, and potential
      solutions that could be pursued by researchers are highlighted. 

PMID- 25850825
TI  - In situ ultrasound imaging of silk hydrogel degradation and neovascularization.
AB  - Ultrasound (US) is a useful technique to monitor morphological and functional
      changes of biomaterial implants without sacrificing the animal. Contrast-enhanced
      ultrasound (CEUS) along with two-dimensional (2D) US were used to characterize
      the biodegradation and neovascularization of silk protein (8 wt%) hydrogel
      implants in rats. Cylinder-shaped silk hydrogel plugs were implanted into the
      space between the hind limb thigh muscles in Wistar rats (n = 6). The increase of
      echogenicity in 2D US revealed tissue-ingrowth-accompanied gel degradation over
      18 weeks. The shape and size of the implanted gels remained qualitatively
      unchanged until week 15, as confirmed by Bland and Altman analysis and
      visualization of retrieved samples. Using CEUS, neovascularization was monitored
      by the presence of microbubbles in the gel area, and the dynamic vascularization
      process was indicated by the contrast enhancement values, which showed a
      relatively low level (< 5 dB) during weeks 1-8 and significantly increased levels
      (around 20 dB at week 15 and > 35 dB at week 18), suggesting that major
      vascularization had occurred in the gel implants by this time point. Histological
      and scanning electron microscopic analysis of explants revealed time-dependent
      increases in the pore size of the gel matrix, the presence of endothelial and red
      blood cells and the number of blood vessels in the gel implants, indicating that
      degradation and vascularization did occur in silk gel implants during the time
      period. The present study demonstrates the use of US imaging for monitoring of in
      vivo degradation and vascularization of silk implants in a non-destructive way.
      Copyright (c) 2015 John Wiley & Sons, Ltd.

PMID- 25850826
TI  - Incidence and severity of reported acute sports injuries in 35 sports using
      insurance registry data.
AB  - Acute injuries in sport are still a problem where limited knowledge of incidence
      and severity in different sports at national level exists. In Sweden, 80% of the
      sports federations have their mandatory injury insurance for all athletes in the
      same insurance company and injury data are systematically kept in a national
      database. The aim of the study was to identify high-risk sports with respect to
      incidence of acute and severe injuries in 35 sports reported to the database. The
      number and incidences of injuries as well as injuries leading to permanent
      medical impairment (PMI) were calculated during 2008-2011. Each year
      approximately 12,000 injuries and 1,162,660 licensed athletes were eligible for
      analysis. Eighty-five percent of the injuries were reported in football, ice
      hockey, floorball, and handball. The highest injury incidence as well as PMI was
      in motorcycle, handball, skating, and ice hockey. Females had higher risk of a
      PMI compared with males in automobile sport, handball, floorball, and football.
      High-risk sports with numerous injuries and high incidence of PMI injuries were
      motorcycle, handball, ice hockey, football, floorball, and automobile sports.
      Thus, these sports ought to be the target of preventive actions at national
      level.

PMID- 25850827
TI  - Cochrane reviewers' response to Alper and colleagues' analysis of thrombolysis in
      acute ischaemic stroke.

PMID- 25850828
TI  - Betatrophin levels are increased in women with gestational diabetes mellitus
      compared to healthy pregnant controls.
AB  - OBJECTIVE: Betatrophin has recently been introduced as a novel
      adipokine/hepatokine, which promotes pancreatic beta cell proliferation and
      improves glucose tolerance in several mouse models of insulin resistance.
      However, regulation of betatrophin in gestational diabetes mellitus (GDM), as
      well as its association with markers of obesity, such as glucose and lipid
      metabolism, inflammation, and renal function, have not been elucidated. DESIGN
      AND METHODS: Circulating betatrophin was quantified in 74 women with GDM and 74
      healthy and gestational age-matched controls by ELISA. In a subset of the study
      population comprising of 85 patients (41 previous controls, 44 previous women
      with GDM), postpartum betatrophin levels were measured in a follow-up study.
      RESULTS: Median (interquartile range) serum betatrophin levels were higher in
      women with GDM (1.79 (0.53) MUg/l) as compared to non-diabetic pregnant controls
      (1.58 (0.44) MUg/l) (P=0.002). In multivariate analysis, GDM status was an
      independent and positive predictor of circulating betatrophin (P=0.001).
      Furthermore, betatrophin levels were significantly higher during gestation (1.70
      (0.53) MUg/l) as compared to postpartum levels (1.55 (0.66) MUg/l) (P=0.028).
      Moreover, postpartum irisin remained a positive and independent predictor of
      postpartum betatrophin concentrations. CONCLUSIONS: Women with GDM have
      significantly higher betatrophin levels as compared to healthy pregnant controls
      and GDM status positively predicts circulating betatrophin. Furthermore,
      postpartum levels are significantly lower as compared to betatrophin
      concentrations during pregnancy. Moreover, irisin is a significant predictor of
      postpartum betatrophin levels.

PMID- 25850829
TI  - Novel inflammatory biomarkers in primary hyperparathyroidism.
AB  - OBJECTIVE: Primary hyperparathyroidism (PHPT) has been associated with low-grade
      inflammation and increased risk of cardiovascular disease (CVD). The aim of the
      study was to investigate systemic levels of pro-inflammatory proteins that
      previously have not been examined in patients with PHPT. The selection of the pro
      inflammatory biomarkers included in this study, MMP9, S100A4, S100A8/A9 and the
      receptors sCD14 and RAGE, was based on a previous microarray screen of mRNAs in
      adipose tissue from PHPT patients. DESIGN: A prospective study was conducted on a
      total of 57 patients with PHPT and a control group of 20 healthy blood donors.
      METHODS: PHPT patients with normalisation of serum calcium levels after
      parathyroidectomy were followed for 6 months. Forty-two patients participated in
      the longitudinal study, in which blood samples were taken at inclusion, and 1, 3
      and 6 months after surgery. RESULTS: We observed increased serum levels of MMP9
      (P=0.029), S100A4 (P<0.001) and sCD14 (P=0.002) in the 57 patients with PHPT
      compared to the control-group. During 6 months of follow up, S100A4 (P=0.022) and
      sCD14 (0.002) decreased significantly, while serum levels of MMP9 increased
      (P=0.025). CONCLUSIONS: The results demonstrate an increased inflammatory
      response in PHPT patients shown by elevated MMP9, S100A4 and sCD14 at inclusion.
      During the 6 months of follow-up, MMP9 increased further, possibly due to the
      tissue repair process after parathyroidectomy. S100A4 and sCD14 decreased after
      surgery demonstrating a partial reversal of the systemic inflammation.

PMID- 25850830
TI  - O2 sensing dynamics of BiFeO3 nanofibers: effect of minor carrier compensation.
AB  - In this paper we investigate O(2) sensing dynamics in BiFeO(3) (BFO) nanofibers
      at various concentrations and temperatures, by using a combined experiment and
      computer simulation approach. Samples of pristine BFO, Ni-doped BFO, and Pb-doped
      BFO nanofibers were prepared. By incorporating Ni and Pb, additional acceptor
      states are introduced in BFO. Density functional theory calculations show that Ni
      prefers to substitute Fe site while Pb substitutes Bi site, resulting in a new
      deep donor originating from Ni interstitial defects, along with oxygen vacancies
      (V(o)). We find that both the sensing response and recovery time are shorter in
      samples made of pristine BFO nanofibers than in Ni- and Pb-doped nanofiber
      samples. We interpret the observed sensing dynamics through charge transport
      theory of the major (acceptors) and minor (donors) carriers, and found that the
      minor carrier compensation plays a significant role in determining the response
      and recovery time of the sensor device. This minor carrier compensation charge
      transport mechanism will provide new insights into more robust sensor development
      strategies, and into the research of ion-electron coupling in chemical dynamics
      of semiconductors.

PMID- 25850832
TI  - Endoscopic ultrasound-guided fine needle aspiration is highly accurate for the
      diagnosis of perirectal recurrence of colorectal cancer.
AB  - BACKGROUND: Endoscopic ultrasound-guided fine needle aspiration is highly
      accurate for the diagnosis of malignancies surrounding the gastrointestinal
      tract. There is a lack of information on the usefulness of this technique in the
      diagnosis of colorectal cancer recurrence. OBJECTIVE: The purpose of this work
      was to investigate the performance characteristics of endoscopic ultrasound
      guided fine needle aspiration for the cytologic diagnosis of perirectal
      recurrence of colorectal cancer. DESIGN: This was a retrospective study on the
      clinical and radiologic suspicion of perirectal recurrence of colorectal cancer.
      SETTINGS: The study was conducted at 4 tertiary hospitals. PATIENTS: Consecutive
      patients with suspicion of perirectal recurrence of colorectal cancer undergoing
      endoscopic ultrasound-guided fine needle aspiration between 2000 and 2013 were
      included in this study. INTERVENTIONS: The study intervention was endoscopic
      ultrasound-guided fine needle aspiration. MAIN OUTCOME MEASURES: Endoscopic
      ultrasound-guided fine needle aspiration performance characteristics and outcome
      (malignant or benign) were analyzed. The gold standard was cytologic results if
      malignancy or follow-up if benignity. RESULTS: A total of 58 patients were
      included (32 men; mean age, 64.2 +/- 10.0 years [range, 44-88 years]). The
      location of the initial neoplasm was the rectum for 42 patients and the colon for
      16 patients. Endoscopic ultrasound findings included a mass in the anastomosis (n
      = 8), perirectal fat (n = 23), lymph nodes (n = 20), or asymmetric thickness of
      the rectal wall (n = 6). Cytology showed malignancy in 38 patients (67%), benign
      features in 17 (30%), and was not evaluable in 2. Mean follow-up to confirm a
      benign outcome was 51.3 +/- 30.3 months (range, 5.2-180.0 months). Final outcome
      was recurrence in 40 patients (69%) and benignity in 18 patients (31%).
      Performance characteristics of endoscopic ultrasound-guided fine needle
      aspiration were sensitivity (97%), specificity (100%), positive predictive value
      (100%), negative predictive value (94%), and accuracy (98%). In the intention to
      diagnose analysis, the corresponding values were 95%, 100%, 100%, 90%, and 96%.
      LIMITATIONS: This was a retrospective series with a limited number of patients.
      CONCLUSIONS: Endoscopic ultrasound-guided fine needle aspiration is a highly
      accurate tool for the cytologic diagnosis of perirectal recurrence in patients
      with previous colorectal cancer.

PMID- 25850831
TI  - DOF AFFECTING GERMINATION 2 is a positive regulator of light-mediated seed
      germination and is repressed by DOF AFFECTING GERMINATION 1.
AB  - BACKGROUND: The transcription factor DOF AFFECTING GERMINATION1 (DAG1) is a
      repressor of the light-mediated seed germination process. DAG1 acts downstream
      PHYTOCHROME INTERACTING FACTOR3-LIKE 5 (PIL5), the master repressor, and
      negatively regulates gibberellin biosynthesis by directly repressing the
      biosynthetic gene AtGA3ox1. The Dof protein DOF AFFECTING GERMINATION (DAG2)
      shares a high degree of aminoacidic identity with DAG1. While DAG1 inactivation
      considerably increases the germination capability of seeds, the dag2 mutant has
      seeds with a germination potential substantially lower than the wild-type,
      indicating that these factors may play opposite roles in seed germination.
      RESULTS: We show here that DAG2 expression is positively regulated by
      environmental factors triggering germination, whereas its expression is repressed
      by PIL5 and DAG1; by Chromatin Immuno Precipitation (ChIP) analysis we prove that
      DAG1 directly regulates DAG2. In addition, we show that Red light significantly
      reduces germination of dag2 mutant seeds. CONCLUSIONS: In agreement with the seed
      germination phenotype of the dag2 mutant previously published, the present data
      prove that DAG2 is a positive regulator of the light-mediated seed germination
      process, and particularly reveal that this protein plays its main role downstream
      of PIL5 and DAG1 in the phytochrome B (phyB)-mediated pathway.

PMID- 25850833
TI  - Adenocarcinoma of the rectum in patients under age 40 is increasing: impact of
      signet-ring cell histology.
AB  - BACKGROUND: Overall, the incidence of colorectal cancer appears to be stable or
      diminishing. However, based on our practice pattern, we observed that the
      incidence of rectal cancer in patients under 40 is increasing and may be
      associated with a prominence of signet-ring cell histology. OBJECTIVE: The aim of
      this study was to verify the rising trend in rectal cancer in patients under 40
      and describe the histology prominent in that cohort. DESIGN: This is a
      retrospective cohort study. SETTING AND PATIENTS: We performed a retrospective
      cohort study of all patients diagnosed with rectal adenocarcinoma from 1980 to
      2010 using the Surveillance, Epidemiology, and End Results cancer registry. MAIN
      OUTCOME MEASURES: Rectal cancer incidence, histology, and associated staging
      characteristics were the primary outcomes measured. RESULTS: Although the
      incidence of rectal cancer for all ages remained stable from 1980 to 2010, we
      observed an annual percent change of +3.6% in the incidence of rectal cancer in
      patients under 40. The prevalence of signet cell histology in patients under 40
      was significantly greater than in patients over 40 (3% vs 0.87%, p < 0.01). A
      multivariate regression analysis revealed an adjusted odds ratio of 3.6 (95% CI,
      2.6-5.1) for signet cell histology in rectal adenocarcinoma under age 40. Signet
      cell histology was also significantly associated with a more advanced stage at
      presentation, poorly differentiated tumor grade, and worse prognosis compared
      with mucinous and nonmucinous rectal adenocarcinoma. LIMITATIONS: The study was
      limited by its retrospective nature and the information available in the
      Surveillance, Epidemiology, and End Results database. CONCLUSIONS: Despite a
      stable incidence of rectal cancer for all ages, the incidence in patients under
      40 has quadrupled since 1980, and cancers in this group are 3.6 times more likely
      to have signet cell histology. Given the worse outcomes associated with signet
      cell histology, these data highlight a need for thorough evaluation of young
      patients with rectal symptoms.

PMID- 25850834
TI  - Feasibility of modified short-course radiotherapy combined with a
      chemoradiosensitizer for T3 rectal cancer.
AB  - BACKGROUND: 5-Fluorouracil-based chemotherapy is considered to be a
      radiosensitizer; however, conventional short-course radiotherapy combined with
      chemotherapy is generally thought to not be feasible because of the prevalence of
      side effects. OBJECTIVE: The aim of this study was to evaluate the feasibility of
      modified short-course radiotherapy combined with a chemoradiosensitizer for T3
      rectal cancer. DESIGN AND SETTINGS: This study was retrospective in nature and
      used a prospectively collected database. PATIENTS: Patients with T3 rectal cancer
      located below the peritoneum reflection were selected. INTERVENTIONS: A total
      dose of 25 Gy of radiotherapy was administered in 10 fractions of 2.5 Gy each for
      5 days. Radiotherapy was performed with S-1 as a radiosensitizer from day 1 to
      day 10. Surgery was targeted to be performed 4 weeks after radiotherapy. MAIN
      OUTCOME MEASUREMENTS: The morbidity, sphincter-preserving rate, anal function,
      and long-term outcomes were assessed. RESULTS: All patients (n = 170) completed
      the radiotherapy regimen and 166 (97.6%) completed the combination regimen with
      chemotherapy. A total of 149 patients (87.6%) had sphincter-preserving surgery
      (double stapling technique (DST), 58 patients; intersphincteric resection (ISR),
      91 patients), and postoperative complications were relatively mild (anastomotic
      leakage, 15.4%; intra-abdominal infection, 8.2%). Among those undergoing
      sphincter preserving surgery, the 5-year local relapse-free survival rate was
      94.3% in the DST group, and 89.8% in the ISR group. With respect to the anal
      function, the Wexner score the first year after stoma closure for the double
      stapling technique group was 6 and that for intersphincteric resection was 15;
      however, the score for the intersphincteric resection group was improved to 8 at
      4 years after stoma closure. LIMITATIONS: This study had limitations because it
      was an uncontrolled, 1-arm, retrospective review with a small sample size.
      CONCLUSIONS: Modified short-course radiotherapy combined with
      chemoradiosensitizer is a feasible approach for treating T3 rectal cancer. With
      the use of the short-course approach, efforts to reduce the incidence of side
      effects by appropriately prolonging the waiting period enable the administration
      of combination treatment with short-course radiotherapy and chemotherapy.

PMID- 25850835
TI  - IPAA-related sepsis significantly increases morbidity of ileoanal pouch excision.
AB  - BACKGROUND: Perineal wound complications after ileoanal pouch excision remain a
      significant cause of morbidity. OBJECTIVE: The purpose of this work was to
      describe the incidence, outcomes, and predictors of perineal wound complications
      after pouch excision. DESIGN: This was a retrospective medical chart review.
      SETTINGS: The study was conducted in a single clinical institution. PATIENTS:
      Patients who underwent pouch excision at our institution from July 1992 through
      July 2012 were identified. Patient and perioperative variables were reviewed.
      Multivariate and univariate analyses were undertaken. MAIN OUTCOME MEASURES:
      Perineal wound (including perineal wound infection and persistent perineal sinus
      [nonhealing by 6 months]) and perineal hernia were measured. RESULTS: A total of
      47 patients (mean age, 46 years; 42.6% men) with familial adenomatous polyposis
      (10.6%), mucosal ulcerative colitis (61.7%), or Crohn's disease (27.7%) underwent
      pouch excision, including 36.2% for IPAA-related sepsis (presacral abscess;
      perineal-, sacral-, or pouch-vaginal fistula; and anastomotic defect), 44.7% for
      pouch dysfunction, 10.6% for refractory pouchitis, and 8.5% for neoplasia.
      Fourteen (29.8%) developed perineal wound complications, including 100% perineal
      wound infection, 28.6% persistent perineal sinus, and 7.1% perineal hernia.
      Perineal wound infection was associated with delayed healing (>6 weeks; 71.4% vs
      24.2%; p = 0.002) and IPAA-related sepsis (28.6% vs 0%; p = 0.001). Patients with
      and without perineal wound complications were similar in age, diagnoses, fecal
      diversion, immunosuppression, comorbid conditions, nutrition, and surgical
      variables. Most patients underwent intersphincteric dissection (87.2%) with
      primary perineal closure (97.0%). Perineal wound complications were significantly
      associated with IPAA-related sepsis as an indication for pouch excision (57.1% vs
      27.2%; p = 0.05), intraoperative pouch perforation (35.7% vs 9.1%, p =0.03), and
      smoking (21.4% vs 3.0%; p = 0.04). IPAA-related sepsis and a current smoking
      status (OR, 19.3 [95% CI, 1.8 -488.1]) are significant independent predictors on
      multivariate logistic regression (OR, 6.4 [95% CI, 1.4-30.2]) of perineal wound
      complications. All of the patients with persistent perineal sinus achieved
      successful healing at a median of 734 days (range, 363-2182 days), requiring a
      median of 1.5 procedures. LIMITATIONS: This was a single-center retrospective
      review with a small sample size. CONCLUSIONS: Preoperative IPAA-related sepsis
      and current smoking are significant risk factors for perineal wound complications
      after pouch excision.

PMID- 25850836
TI  - Relationship between model for end-stage liver disease score and 30-day outcomes
      for patients undergoing elective colorectal resections: an American college of
      surgeons-national surgical quality improvement program study.
AB  - BACKGROUND: Patients with liver disease face significant risk of complications
      and death when considering elective colorectal resection for benign or malignant
      indications. OBJECTIVE: We sought to determine the relationship between Model of
      End-Stage Liver Disease score and 30-day outcomes in patients undergoing elective
      colorectal resections. DESIGN: This was a retrospective cohort study. SETTINGS:
      The study included hospitals participating in the National Surgical Quality
      Improvement Program. PATIENTS: Adult patients who underwent elective colorectal
      resection from 2005 to 2011 were identified from the National Surgical Quality
      Improvement Program database. Patients missing laboratory values necessary to
      calculate the Model of End-Stage Liver Disease score were excluded (61% of 81,346
      patients identified). MAIN OUTCOME MEASURES: Differences in patient- and disease
      related characteristics by Model of End-Stage Liver Disease categories were
      assessed with chi analyses. Thirty-day mortality and major morbidity were
      examined using logistic regression. RESULTS: Of 31,950 patients undergoing
      elective colorectal resections (14% including proctectomy), most (60%) were
      performed for colon or rectal cancer; other benign indications included
      diverticulitis (20%), polyp (10%), and IBD (10%). A total of 58% of patients had
      a Model of End-Stage Liver Disease score of >=7. Increasing scores were
      associated with older age; higher BMI; higher ASA class; lower albumin level; and
      higher incidence of diabetes mellitus, pulmonary and cardiac disease,
      hypertension, and dependent functional status. In univariate analysis, patients
      with higher scores had a greater risk of 30-day mortality (score = 6 (0.69%); 7
      11 (1.62%); 11-15 (4.52%); >15, (5.01%); p < 0.0001). After controlling for other
      comorbidities, Model of End-Stage Liver Disease score remained a significant
      predictor of 30-day mortality, major complications, and respiratory
      complications. LIMITATIONS: This was a retrospective analysis of administrative
      data, limiting some access to clinically relevant data. CONCLUSIONS: Consistent
      with previous reports, patients with higher Model of End-Stage Liver Disease
      scores have a significantly higher risk of death and major morbidity in the 30
      days after elective colorectal resection (see Video, Supplemental Digital
      Content, http://links.lww.com/DCR/A180).

PMID- 25850837
TI  - What are the results of colonic volvulus surgery?
AB  - BACKGROUND: Operative results of volvulus are largely unknown because of
      infrequent diagnosis. OBJECTIVE: We examined the results of operative
      intervention for colonic volvulus. DESIGN: We merged trackable data from the
      California Inpatient Database with Supplemental Files for Revisit Analyses
      between January 1, 2005, and December 31, 2007. SETTINGS: Trackable data from
      California discharge records. PATIENTS: We identified all of the patients with
      colonic volvulus who underwent 1 of 4 surgical procedures, including
      manipulation/fixation of the colon, right colectomy, left colectomy, or total
      colectomy. MAIN OUTCOME MEASURES: During the 36-month study period, we identified
      recurrence risk, recurrence requiring reoperation, time to reoperation, stoma
      formation, disposition on discharge, and in-hospital mortality. Fisher exact,
      chi(2), and ANOVA tests were used when appropriate. RESULTS: We identified 2141
      patients with colonic volvulus who were undergoing intraoperative
      manipulation/fixation of the colon (n = 209 (12%)), right (n = 728 (41%)), left
      (n = 781 (44%)), or total colectomy (n = 56 (3%)). Patients treated with
      intraoperative manipulation/fixation were younger, more likely to be women, and
      more likely to have private insurance. Patients who underwent total colectomy had
      the highest risk of mortality (21%), highest risk of stoma creation (64%), and
      longest length of stay (18 days); were more likely to be readmitted (9%); and
      were the most likely to be discharged to a skilled nursing facility (48%).
      Patients treated with intraoperative manipulation/fixation had the lowest
      mortality, risk of stoma formation, length of stay, and likelihood of discharge
      to skilled nursing facility but the highest risk of subsequent procedures for
      volvulus (26%) over a follow-up ranging from 0 to 687 days. LIMITATIONS: This
      study was limited by retrospective study design, heterogeneous patient factors,
      and inability to identify the time of last follow-up. CONCLUSIONS: The majority
      of patients with volvulus underwent a resectional procedure. A subset without
      resection had favorable initial outcomes but remained at high risk for subsequent
      procedures. There may be a potential role for evaluating intraoperative
      manipulation/fixation in a small subset of patients with colonic volvulus.

PMID- 25850838
TI  - Dynamic article: composite antropyloric valve and gracilis muscle transposition
      for total anorectal reconstruction: a preliminary report.
AB  - BACKGROUND: Technique and functional outcomes of anorectal reconstruction using
      an antropyloric graft have been reported previously. This technique had
      reasonable initial outcomes but lacked voluntary function. OBJECTIVE: We hereby
      report the initial results of patients who underwent gracilis muscle wrapping
      around the perineally transposed antropyloric valve in an attempt to improve
      voluntary fecal control. SETTING: This study was conducted at a single tertiary
      care institution. PATIENTS: Eight adult patients (7 men and 1 woman) with a
      median age of 38 years (range, 19-51 years) underwent this procedure. Seven
      patients already had anorectal reconstruction with a transposed antropyloric
      valve, and 1 patient with severely damaged anal sphincter complex underwent
      single-stage composite antropylorus transposition with a gracilis muscle wrap.
      MAIN OUTCOME MEASURES: The primary outcome measures were anatomical integrity and
      functional status of the composite graft in the perineum. RESULTS: No operative
      mortality or serious procedure-related morbidity occurred in any patient. The
      median postoperative resting pressure was 29 mmHg (range, 22-38 mmHg) and squeeze
      pressure was 72.5 mmHg (range, 45-267 mmHg). There was a significant improvement
      in the squeeze pressure following surgery (p = 0.039). Also, the St. Mark's
      incontinence scores significantly improved in all patients and varied between 7
      and 9 (p = 0.003). The ability to defer defecation and the reduced frequency of
      leakage accidents were the prime reasons for improved postgraciloplasty outcomes
      in these patients. On personal interviews, all patients who underwent this
      procedure were satisfied with the results of their surgery. LIMITATIONS: A longer
      follow-up with a larger sample size is required. Quality-of-life data have not
      been evaluated in this study. CONCLUSIONS: Gracilis muscle wrapping around a
      perineally transposed antropyloric valve is possible and improves the voluntary
      control and overall functional outcomes in a select group of patients with end
      stage fecal incontinence requiring anal replacement (Supplemental Digital Content
      1, http://links.lww.com/DCR/A173).

PMID- 25850839
TI  - Functional and histological evidence for the targeted therapy using biocompatible
      polycaprolactone beads and autologous myoblasts in a dog model of fecal
      incontinence.
AB  - BACKGROUND: Injection of bulking agents into the anal canal is limited by several
      factors, including biological resorption, particle migration, and ongoing
      degradation of the injected bulking agent. OBJECTIVE: We investigated whether an
      injection of polycaprolactone beads containing autologous myoblasts could improve
      sphincter function in a dog model of fecal incontinence. DESIGN: The control sham
      surgery group underwent skin incision around the anal sphincter (n = 5). Fecal
      incontinence was induced by resecting 25% of the posterior internal/external anal
      sphincter in another 10 dogs. After 1 month of sphincter injury, dogs were then
      treated with (n = 5) or without (n = 5) polycaprolactone beads containing PKH-26
      labeled autologous myoblasts. SETTING: This study was conducted at the department
      of surgery in collaboration with the department of advanced materials. OUTCOME
      MEASURES: Three months after injection treatment, the resting and contractile
      pressure differences of the anal sphincter were compared, and histopathological
      studies were performed. RESULTS: The anal pressures in untreated dogs were
      significantly lower than those in the sham surgery group (p < 0.05). The resting
      and contractile pressure differences were higher in treated dogs than in
      untreated dogs (resting pressure difference: 0.7 +/- 0.5 vs -0.6 +/- 0.8 mmHg;
      coefficient of the difference in recovery rate, 0.38; 95% CI, 0.15-0.61, p =
      0.001; contractile pressure difference: 1.1 +/- 4.2 vs -3.9 +/- 2.6 mmHg;
      coefficient, 1.63; 95% CI, 0.55-2.71, p = 0.003). Immunofluorescent staining
      confirmed that the myoblasts had differentiated and synthesized myosin heavy
      chain, as observed in vitro. LIMITATIONS: This study was limited by the lack of
      comparison of injecting beads containing autologous myoblasts with injecting
      myoblasts alone. CONCLUSION: This study shows that an injection of
      polycaprolactone beads containing autologous myoblasts may improve anal sphincter
      function in an animal model of fecal incontinence.

PMID- 25850841
TI  - Long-term follow-up after surgery for simple and complex cryptoglandular
      fistulas: fecal incontinence and impact on quality of life.
AB  - BACKGROUND: Surgical management of cryptoglandular fistulas is a challenge
      because the consequences of anal surgery potentially include fecal incontinence
      and impaired quality of life. OBJECTIVE: To assess factors associated with fecal
      incontinence after surgery for simple and complex cryptoglandular fistulas and to
      determine the impact of incontinence on quality of life. DESIGN: The design is
      retrospective and cross-sectional. SETTINGS: This study was conducted at an
      academic tertiary center and at a private center specializing in proctologic
      surgery. PATIENTS: All patients who underwent preoperative endoanal ultrasound
      for cryptoglandular fistula between 2002 and 2012. MAIN OUTCOME MEASURES: A
      questionnaire was sent out in October 2013 to evaluate incontinence (Wexner
      score) and its impact on quality of life (FIQL). Variables tested for association
      were patient demographics, fistula type, number of incised abscesses (0, 1, >1),
      number of fistulotomies (0, 1, >1) and number of sphincter-sparing procedures (0,
      1, >1). RESULTS: Of the 141 patients participating, 116 (82%; 76 men, 40 women)
      returned all the questionnaires. Median follow-up from the first perianal fistula
      surgery was 7.8 years (range, 2.1-18.1 years). Thirty-nine patients (34%)
      experienced incontinence. Surgical fistulotomy, multiple abscess drainages and a
      high transsphincteric or suprasphincteric fistula tract were associated with
      incontinence. As compared to simple fistula (Wexner score, 1.2 [SD, 2.1]),
      incontinence was worse after surgery for complex fistula (Wexner score, 4.7 [SD,
      6.2], p = 0.001), as were quality of life elements, including lifestyle (p =
      0.030), depression (p = 0.077) and embarrassment (p < 0.001). LIMITATIONS: Mainly
      retrospective design without a standardized treatment protocol. CONCLUSION:
      Surgical fistulotomy is the strongest risk factor for fecal incontinence. The
      severity of incontinence increases with the complexity of the fistula, negatively
      influencing quality of life. Special attention should be paid to these patients
      so as to mitigate symptoms later in life. A shift to sphincter-sparing procedures
      appears warranted.

PMID- 25850842
TI  - Potential problems with the public reporting of risk-adjusted surgical outcomes.

PMID- 25850843
TI  - Outcome science.

PMID- 25850840
TI  - Factors that influence minority use of high-volume hospitals for colorectal
      cancer care.
AB  - BACKGROUND: Previous studies suggest that minorities cluster in low-quality
      hospitals despite living close to better performing hospitals. This may
      contribute to persistent disparities in cancer outcomes. OBJECTIVE: The purpose
      of this work was to examine how travel distance, insurance status, and
      neighborhood socioeconomic factors influenced minority underuse of high-volume
      hospitals for colorectal cancer. DESIGN: The study was a retrospective, cross
      sectional, population-based study. SETTINGS: All hospitals in California from
      1996 to 2006 were included. PATIENTS: Patients with colorectal cancer diagnosed
      and treated in California between 1996 and 2006 were identified using California
      Cancer Registry data. MAIN OUTCOME MEASURES: Multivariable logistic regression
      models predicting high-volume hospital use were adjusted for age, sex, race,
      stage, comorbidities, insurance status, and neighborhood socioeconomic factors.
      RESULTS: A total of 79,231 patients treated in 417 hospitals were included in the
      study. High-volume hospitals were independently associated with an 8% decrease in
      the hazard of death compared with other settings. A lower proportion of
      minorities used high-volume hospitals despite a higher proportion living nearby.
      Although insurance status and socioeconomic factors were independently associated
      with high-volume hospital use, only socioeconomic factors attenuated differences
      in high-volume hospital use of black and Hispanic patients compared with white
      patients. LIMITATIONS: The use of cross-sectional data and racial and ethnic
      misclassifications were limitations in this study. CONCLUSIONS: Minority patients
      do not use high-volume hospitals despite improved outcomes and geographic access.
      Low socioeconomic status predicts low use of high-volume settings in select
      minority groups. Our results provide a roadmap for developing interventions to
      increase the use of and access to higher quality care and outcomes. Increasing
      minority use of high-volume hospitals may require community outreach programs and
      changes in physician referral practices.

PMID- 25850844
TI  - Should agraffectomy always be recommended to treat chronic sequelae following
      stapled anorectal procedures?

PMID- 25850845
TI  - The authors reply.

PMID- 25850846
TI  - Slaughtering sacred cows: long-term surveillance after ileal pouch-anal
      anastomosis for ulcerative colitis and choice of anastomosis.

PMID- 25850847
TI  - The authors reply.

PMID- 25850848
TI  - Time to Rethink ELAPE?

PMID- 25850849
TI  - Must we continue to look for excuses?

PMID- 25850850
TI  - Prevention of anal cancer -- can we do better?

PMID- 25850851
TI  - Variation in lynch syndrome.

PMID- 25850855
TI  - Morphine potentiates LPS-induced autophagy initiation but inhibits autophagosomal
      maturation through distinct TLR4-dependent and independent pathways.
AB  - AIM: Opioids are the most prescribed analgesics for moderate and severe pain
      management; however, chronic use impairs host innate immune response and
      increases susceptibility to infection. Recently, autophagy has been shown to be
      an innate defence mechanism against bacterial infection. The effect of autophagy
      induced bacterial clearance following morphine treatment has not been previously
      investigated. METHODS: Autophagosomes were visualized by confocal microscopy
      following GFP-LC3 transfection and also by transmission electron microscopy. The
      relative protein levels were analysed by Western blot. Macrophages were
      transfected with GFP-mcherry-LC3 simultaneously to monitor autolysosome formation
      and subsequent events that lead to degradation. RESULTS: Morphine treatment
      potentiated LPS-induced vesicular translocation of GFP-LC3 with a concurrent
      increase in LC3-II levels. In addition, morphine upregulated LPS-induced Beclin1
      level, but downregulated Bcl-2 level. We further show that p38 MAP kinase
      signalling is required for autophagy activation. In contrast, morphine inhibited
      LPS-induced autophagosome maturation and autophagolysosomal fusion as indicated
      by the failure to recruit LAMP1 into autophagosome and reduced degradation of
      SQSTM1/p62 protein level. Morphine modulation of LPS-induced autophagosome
      maturation visualized using co-localization of GFP-mcherry-LC3 was TLR4
      independent, but mediated through MU opioid receptor signalling. Correspondingly,
      morphine and LPS co-treatment significantly increased Streptococcus pneumoniae
      load, when compared with LPS treatment alone. CONCLUSION: These observations
      imply that although morphine treatment facilitates LPS-induced autophagy, it
      inhibits autophagolysosomal fusion leading to decreased bacterial clearance and
      increased bacterial load. These observations support the increased susceptibility
      to infection and the prevalence of persistent infection in the drug abuse
      population.

PMID- 25850857
TI  - Reflections on impact issues.

PMID- 25850856
TI  - Transcriptional profile of the human pathogenic fungus Paracoccidioides lutzii in
      response to sulfamethoxazole.
AB  - Paracoccidioidomycosis (PCM) is the most prevalent mycosis in Latin America and
      is caused by a group of fungi within the Paracoccidioides genus. The disease may
      present clinical and pathological manifestations ranging from asymptomatic
      pneumonia pulmonary lesions, to disseminated forms involving multiple organs.
      Sulfonamides were the first drugs used to treat PCM and are still used against
      this fungal infection. Sulfa drugs are competitive antagonists of rho
      aminobenzoic acid (PABA), a reaction catalyzed by dihydropteroate synthase
      (DHPS). However, the molecular effects of sulfonamides against the
      Paracoccidioides genus are unknown. The aim of this work was to investigate the
      global mechanism of action of sulfamethoxazole on Paracoccidioides lutzii. Yeast
      cells were grown on minimum medium in the presence or absence of sulfamethoxazole
      to construct EST libraries. The representational difference analysis (RDA)
      technique was used to identify up- and down-regulated P. lutzii genes after
      treatment with sulfamethoxazole. Approximately six transcripts related to
      mitochondrial function were differentially expressed. To confirm the RDA and
      bioinformatics results, several relevant genes were studied with quantitative
      real-time polymerase chain reaction (qRT-PCR) to evaluate their levels of
      expression. To confirm the impact of sulfamethoxazole on mitochondria, we
      measured the reduction of tetrazolium salt 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) by P. lutzii with or without exposure to the
      drug. MTT assays reveal that sulfamethoxazole produces a marked dose-dependent
      adverse effect on P. lutzii. The transcriptional activity of selected genes in
      infected macrophages corroborated our in vitro results. The results indicated
      that sulfamethoxazole acts in P. lutzii as a competitor for amino acid, nucleic
      acids and folate cofactor biosynthesis, disrupting mitochondrial functions. 

PMID- 25850858
TI  - Women outperform men in remembering to remember.
AB  - The study of gender differences in prospective memory (i.e., remembering to
      remember) has received modest attention in the literature. The few reported
      studies investigating either subjective or objective evaluations of prospective
      memory have shown inconsistent data. In this study, we aimed to verify the
      presence of gender differences during the performance of an objective prospective
      memory test by considering the weight of specific variables such as length of
      delay, type of response, and type of cue. We submitted a sample of 100 healthy
      Italian participants (50 men and 50 women) to a test expressly developed to
      assess prospective memory: The Memory for Intentions Screening Test. Women
      performed better than men in remembering to do an event-based task (i.e.,
      prompted by an external event) and when the task required a physical response
      modality. We discuss the behavioural differences that emerged by considering the
      possible role of sociological, biological, neuroanatomical, and methodological
      variables. 

PMID- 25850859
TI  - Probability Elicitation Under Severe Time Pressure: A Rank-Based Method.
AB  - Probability elicitation protocols are used to assess and incorporate subjective
      probabilities in risk and decision analysis. While most of these protocols use
      methods that have focused on the precision of the elicited probabilities, the
      speed of the elicitation process has often been neglected. However, speed is also
      important, particularly when experts need to examine a large number of events on
      a recurrent basis. Furthermore, most existing elicitation methods are numerical
      in nature, but there are various reasons why an expert would refuse to give such
      precise ratio-scale estimates, even if highly numerate. This may occur, for
      instance, when there is lack of sufficient hard evidence, when assessing very
      uncertain events (such as emergent threats), or when dealing with politicized
      topics (such as terrorism or disease outbreaks). In this article, we adopt an
      ordinal ranking approach from multicriteria decision analysis to provide a fast
      and nonnumerical probability elicitation process. Probabilities are subsequently
      approximated from the ranking by an algorithm based on the principle of maximum
      entropy, a rule compatible with the ordinal information provided by the expert.
      The method can elicit probabilities for a wide range of different event types,
      including new ways of eliciting probabilities for stochastically independent
      events and low-probability events. We use a Monte Carlo simulation to test the
      accuracy of the approximated probabilities and try the method in practice,
      applying it to a real-world risk analysis recently conducted for DEFRA (the U.K.
      Department for the Environment, Farming and Rural Affairs): the prioritization of
      animal health threats. 

PMID- 25850860
TI  - The Plasmodium falciparum exportome contains non-canonical PEXEL/HT proteins.
AB  - The pathogenicity of Plasmodium falciparum is partly due to parasite-induced host
      cell modifications. These modifications are facilitated by exported P. falciparum
      proteins, collectively referred to as the exportome. Export of several hundred
      proteins is mediated by the PEXEL/HT, a protease cleavage site. The PEXEL/HT is
      usually comprised of five amino acids, of which R at position 1, L at position 3
      and E, D or Q at position 5 are conserved and important for export. Non-canonical
      PEXEL/HTs with K or H at position 1 and/or I at position 3 are presently
      considered non-functional. Here, we show that non-canonical PEXEL/HT proteins are
      overrepresented in P. falciparum and other Plasmodium species. Furthermore, we
      show that non-canonical PEXEL/HTs can be cleaved and can promote export in both a
      REX3 and a GBP reporter, but not in a KAHRP reporter, indicating that non
      canonical PEXEL/HTs are functional in concert with a supportive sequence
      environment. We then selected P. falciparum proteins with a non-canonical
      PEXEL/HT and show that some of these proteins are exported and that their export
      depends on non-canonical PEXEL/HTs. We conclude that PEXEL/HT plasticity is
      higher than appreciated and that non-canonical PEXEL/HT proteins cannot
      categorically be excluded from Plasmodium exportome predictions. 

PMID- 25850862
TI  - Beyond molecules: mesoporous supramolecular frameworks self-assembled from
      coordination cages and inorganic anions.
AB  - Biological function arises by the assembly of individual biomolecular modules
      into large aggregations or highly complex architectures. A similar strategy is
      adopted in supramolecular chemistry to assemble complex and highly ordered
      structures with advanced functions from simple components. Here we report a
      series of diamond-like supramolecular frameworks featuring mesoporous cavities,
      which are assembled from metal-imidazolate coordination cages and various anions.
      Small components (metal ions, amines, aldehydes, and anions) are assembled into
      the hierarchical complex structures through multiple interactions including
      covalent bonds, dative bonds, and weak C-H???X (X=O, F, and pi) hydrogen bonds.
      The mesoporous cavities are large enough to trap organic dye molecules,
      coordination cages, and vitamin B12. The study is expected to inspire new types
      of crystalline supramolecular framework materials based on coordination motifs
      and inorganic ions.

PMID- 25850861
TI  - Know your tools--concordance of different methods for measuring brain volume
      change after ischemic stroke.
AB  - INTRODUCTION: Longitudinal brain volume changes have been investigated in a
      number of cerebral disorders as a surrogate marker of clinical outcome. In
      stroke, unique methodological challenges are posed by dynamic structural changes
      occurring after onset, particularly those relating to the infarct lesion. We
      aimed to evaluate agreement between different analysis methods for the
      measurement of post-stroke brain volume change, and to explore technical
      challenges inherent to these methods. METHODS: Fifteen patients with anterior
      circulation stroke underwent magnetic resonance imaging within 1 week of onset
      and at 1 and 3 months. Whole-brain as well as grey- and white-matter volume were
      estimated separately using both an intensity-based and a surface watershed-based
      algorithm. In the case of the intensity-based algorithm, the analysis was also
      performed with and without exclusion of the infarct lesion. Due to the effects of
      peri-infarct edema at the baseline scan, longitudinal volume change was measured
      as percentage change between the 1 and 3-month scans. Intra-class and concordance
      correlation coefficients were used to assess agreement between the different
      analysis methods. Reduced major axis regression was used to inspect the nature of
      bias between measurements. RESULTS: Overall agreement between methods was modest
      with strong disagreement between some techniques. Measurements were variably
      impacted by procedures performed to account for infarct lesions. CONCLUSIONS:
      Improvements in volumetric methods and consensus between methodologies employed
      in different studies are necessary in order to increase the validity of
      conclusions derived from post-stroke cerebral volumetric studies. Readers should
      be aware of the potential impact of different methods on study conclusions.

PMID- 25850863
TI  - The Use of Pediatric Ventricular Assist Devices in Children's Hospitals From 2000
      to 2010: Morbidity, Mortality, and Hospital Charges.
AB  - OBJECTIVE: The use of ventricular assist devices has increased dramatically in
      adult heart failure patients. However, the overall use, outcome, comorbidities,
      and resource utilization of ventricular assist devices in pediatric patients have
      not been well described. We sought to demonstrate that the use of ventricular
      assist devices in pediatric patients has increased over time and that mortality
      has decreased. DESIGN: A retrospective study of the Pediatric Health Information
      System database was performed for patients 20 years old or younger undergoing
      ventricular assist device placement from 2000 to 2010. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: Four hundred seventy-five pediatric patients were
      implanted with ventricular assist devices during the study period: 69 in 2000
      2003 (era 1), 135 in 2004-2006 (era 2), and 271 in 2007-2010 (era 3). Median age
      at ventricular assist device implantation was 6.0 years (interquartile range, 0.5
      13.8), and the proportion of children who were 1-12 years old increased from 29%
      in era 1 to 47% in era 3 (p = 0.002). The majority of patients had a diagnosis of
      cardiomyopathy; this increased from 52% in era 1 to 72% in era 3 (p = 0.003).
      Comorbidities included arrhythmias (48%), pulmonary hypertension (16%), acute
      renal failure (34%), cerebrovascular disease (28%), and sepsis/systemic
      inflammatory response syndrome (34%). Two hundred forty-seven patients (52%)
      underwent heart transplantation and 327 (69%) survived to hospital discharge.
      Hospital mortality decreased from 42% in era 1 to 25% in era 3 (p = 0.004).
      Median hospital length of stay increased (37 d [interquartile range, 12-64 d] in
      era 1 vs 69 d [interquartile range, 35-130] in era 3; p < 0.001) and median
      adjusted hospital charges increased ($630,630 [interquartile range, $227,052
      $853,318] in era 1 vs $1,577,983 [interquartile range, $874,463-$2,280,435] in
      era 3; p < 0.001). Factors associated with increased mortality include age less
      than 1 year (odds ratio, 2.04; 95% CI, 1.01-3.83), acute renal failure (odds
      ratio, 2.1; 95% CI, 1.26-3.65), cerebrovascular disease (odds ratio, 2.1; 95% CI,
      1.25-3.62), and extracorporeal membrane oxygenation (odds ratio, 3.16; 95% CI,
      1.79-5.60). Ventricular assist device placement in era 3 (odds ratio, 0.3; 95%
      CI, 0.15-0.57) and a diagnosis of cardiomyopathy (odds ratio, 0.5; 95% CI, 0.32
      0.84), were associated with decreased mortality. Large-volume centers had lower
      mortality (odds ratio, 0.55; 95% CI, 0.34-0.88), lower use of extracorporeal
      membrane oxygenation, and higher charges. CONCLUSIONS: The use of ventricular
      assist devices and survival after ventricular assist device placement in
      pediatric patients have increased over time, with a concomitant increase in
      resource utilization. Age under 1 year, certain noncardiac morbidities, and the
      use of extracorporeal membrane oxygenation are associated with worse outcomes.
      Lower mortality was seen at larger volume ventricular assist device centers.

PMID- 25850864
TI  - A Case-Control Study on the Impact of Ventilator-Associated Tracheobronchitis in
      the PICU.
AB  - OBJECTIVES: Hospital-acquired infections increase morbidity, mortality, and
      charges in the PICU. We implemented a quality improvement bundle directed at
      ventilator-associated pneumonia in our PICU in 2005. We observed an increase in
      ventilator-associated tracheobronchitis coincident with the near-elimination of
      ventilator-associated pneumonia. The impact of ventilator-associated
      tracheobronchitis on critically ill children has not been previously described.
      Accordingly, we hypothesized that ventilator-associated tracheobronchitisis
      associated with increased length of stay, mortality, and hospital charge. DESIGN:
      Retrospective case-control study. PATIENTS: Critically ill children admitted to a
      quaternary PICU at a free-standing academic children's hospital in the United
      States. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We conducted a
      retrospective case control study, with institutional review board approval, of 77
      consecutive cases of ventilator-associated tracheobronchitis admitted to our PICU
      from 2004-2010. We matched each case with a control based on the following
      criteria (in rank order): age range (< 30 d, 30 d to 24 mo, 24 mo to 12 yr, > 12
      yr), admission Pediatric Risk of Mortality III score +/- 10, number of ventilator
      days of control group (> 75% of days until development of ventilator-associated
      tracheobronchitis), primary diagnosis, underlying organ system dysfunction,
      surgical procedure, and gender. The primary outcome measured was PICU length of
      stay. Secondary outcomes included ventilator days, hospital length of stay,
      mortality, and PICU and hospital charges. Data was analyzed using chi square
      analysis and p less than 0.05 was considered significant. We successfully matched
      45 of 77 ventilator-associated tracheobronchitis patients with controls. There
      were no significant differences in age, gender, diagnosis, or Pediatric Risk of
      Mortality III score between groups. Ventilator-associated tracheobronchitis
      patients had a longer PICU length of stay (median, 21.5 d, interquartile range,
      24 d) compared to controls (median, 18 d; interquartile range, 17 d), although
      not statistically significant (p = 0.13). Ventilator days were also longer in the
      ventilator-associated tracheobronchitis patients (median, 17 d; IQR, 22 d) versus
      control (median, 10.5 d; interquartile range, 13 d) (p = 0.01). There was no
      significant difference in total hospital length of stay (54 d vs 36 d; p = 0.69).
      PICU mortality was higher in the ventilator-associated tracheobronchitis group
      (15% vs 5%; p = 0.14), although not statistically significant. There was an
      increase in both median PICU charges ($197,393 vs $172,344; p < 0.05) and
      hospital charges ($421,576 vs $350,649; p < 0.05) for ventilator-associated
      tracheobronchitis patients compared with controls. CONCLUSIONS: Ventilator
      associated tracheobronchitis is a clinically significant hospital-acquired
      infection in the PICU and is associated with longer duration of mechanical
      ventilation and healthcare costs, possibly through causing a longer PICU length
      of stay. Quality improvement efforts should be directed at reducing the incidence
      of ventilator-associated tracheobronchitis in the PICU.

PMID- 25850865
TI  - Tight Glycemic Control With Insulin Does Not Affect Skeletal Muscle Degradation
      During the Early Postoperative Period Following Pediatric Cardiac Surgery.
AB  - OBJECTIVE: Critical illness is associated with significant catabolism, and
      persistent protein loss correlates with increased morbidity and mortality.
      Insulin is a potent anticatabolic hormone; high-dose insulin decreases skeletal
      muscle protein breakdown in critically ill pediatric surgical patients. However,
      insulin's effect on protein catabolism when given at clinically utilized doses
      has not been studied. The objective was to evaluate the effect of postoperative
      tight glycemic control and clinically dosed insulin on skeletal muscle
      degradation in children after cardiac surgery with cardiopulmonary bypass.
      DESIGN: Secondary analysis of a two-center, prospective randomized trial
      comparing tight glycemic control with standard care. Randomization was stratified
      by study center. PATIENTS: Children 0-36 months who were admitted to the ICU
      after cardiac surgery requiring cardiopulmonary bypass. INTERVENTIONS: In the
      tight glycemic control arm, insulin was titrated to maintain blood glucose
      between 80 and 110 mg/dL. Patients in the control arm received standard care.
      Skeletal muscle breakdown was quantified by a ratio of urinary 3-methylhistidine
      to urinary creatinine. MEASUREMENTS AND MAIN RESULTS: A total of 561 patients
      were included: 281 in the tight glycemic control arm and 280 receiving standard
      care. There was no difference in 3-methylhistidine to creatinine between groups
      (tight glycemic control, 249 +/- 127 vs standard care, 253 +/- 112, mean +/- SD
      in MUmol/g; p = 0.72). In analyses restricted to the patients in tight glycemic
      control arm, higher 3-methylhistidine to creatinine correlated with younger age,
      as well as lower weight, weight-for-age z score, length, and body surface area (p
      < 0.005 for each) and lower postoperative day 3 serum creatinine (r = -0.17; p =
      0.02). Sex, prealbumin, and albumin were not associated with 3-methylhistidine to
      creatinine. During urine collection, 245 patients (87%) received insulin.
      However, any insulin exposure did not impact 3-methylhistidine to creatinine (t
      test, p = 0.45), and there was no dose-dependent effect of insulin on 3
      methylhistidine to creatinine (r = -0.03; p = 0.60). CONCLUSION: Although high
      dose insulin has an anabolic effect in experimental conditions, at doses
      necessary to achieve normoglycemia, insulin appears to have no discernible impact
      on skeletal muscle degradation in critically ill pediatric cardiac surgical
      patients.

PMID- 25850866
TI  - Glucocorticoid Receptor Expression in Peripheral WBCs of Critically Ill Children.
AB  - OBJECTIVES: To characterize glucocorticoid receptor expression in peripheral WBCs
      of critically ill children using flow cytometry. DESIGN: Prospective
      observational cohort. SETTING: A university-affiliated, tertiary PICU. PATIENTS:
      Fifty-two critically ill children. INTERVENTIONS: Samples collected for
      measurement of glucocorticoid receptor expression and parallel cortisol levels.
      MEASUREMENTS AND MAIN RESULTS: Subjects with cardiovascular failure had
      significantly lower glucocorticoid receptor expression both in CD4 lymphocytes
      (mean fluorescence intensity, 522 [354-787] vs 830 [511-1,219]; p = 0.036) and
      CD8 lymphocytes (mean fluorescence intensity, 686 [350-835] vs 946 [558-1,511]; p
      = 0.019) compared with subjects without cardiovascular failure. Subjects in the
      upper 50th percentile of Pediatric Risk of Mortality III scores and organ failure
      also had significantly lower glucocorticoid receptor expression in CD4 and CD8
      lymphocytes. There was no linear correlation between cortisol concentrations and
      glucocorticoid receptor expression. CONCLUSIONS: Our study suggests that patients
      with shock and increased severity of illness have lower glucocorticoid receptor
      expression in CD4 and CD8 lymphocytes. Glucocorticoid receptor expression does
      not correlate well with cortisol levels. Future studies could focus on studying
      glucocorticoid receptor expression variability and isoform distribution in the
      pediatric critically ill population as well as on different strategies to
      optimize glucocorticoid response.

PMID- 25850868
TI  - Asymmetric Copper-Catalyzed Vinylogous Mukaiyama Michael Addition of Cyclic
      Dienol Silanes to Unsaturated alpha-Keto Phosphonates.
AB  - A highly stereoselective vinylogous Mukaiyama Michael reaction (VMMR) leading to
      alpha-keto phosphonate-containing gamma-butenolides with two stereogenic centers
      is described. The presented transformation is catalyzed by a combination of a
      commercially available C2 -symmetric bisoxazoline (BOX) ligand and a copper salt
      and tolerates a variety of nucleophiles and electrophiles. The
      stereoselectivities of the reactions are good to excellent and the products are
      obtained in moderate to high yields. 

PMID- 25850869
TI  - Progressive swelling of the maxilla arising in the radiation site of a congenital
      hemangioma in a 63-year-old woman.

PMID- 25850867
TI  - Cerebrospinal Fluid Markers of Macrophage and Lymphocyte Activation After
      Traumatic Brain Injury in Children.
AB  - OBJECTIVES: The magnitude and role of the cellular immune response following
      pediatric traumatic brain injury remains unknown. We tested the hypothesis that
      macrophage/microglia and T-cell activation occurs following pediatric traumatic
      brain injury by measuring cerebrospinal fluid levels of soluble cluster of
      differentiation 163 and ferritin and soluble interleukin-2 receptor alpha,
      respectively, and determined whether these biomarkers were associated with
      relevant clinical variables and outcome. DESIGN: Retrospective analysis of
      samples from an established, single-center cerebrospinal fluid bank. SETTING:
      PICU in a tertiary children's hospital. PATIENTS: Sixty-six pediatric patients
      after severe traumatic brain injury (Glasgow Coma Scale score < 8) who were 1
      month to 16 years old and 17 control patients who were 1 month to 14 years old.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Cerebrospinal fluid levels of
      soluble cluster of differentiation 163, ferritin, and soluble interleukin-2
      receptor alpha were determined by enzyme-linked immunosorbent assay at two time
      points (t1 = 17 +/- 10 hr; t2 = 72 +/- 15 hr) for each traumatic brain injury
      patient. Cerebrospinal fluid levels of soluble cluster of differentiation 163,
      ferritin, and soluble interleukin-2 receptor alpha after traumatic brain injury
      were compared with controls and analyzed for associations with age, patient sex,
      initial Glasgow Coma Scale score, diagnosis of abusive head trauma, the presence
      of hemorrhage on CT scan, and Glasgow Outcome Scale score. Cerebrospinal fluid
      level of soluble cluster of differentiation 163 was increased in traumatic brain
      injury patients at t2 versus t1 and controls (median, 95.4 ng/mL [interquartile
      range, 21.8-134.0 ng/mL] vs 31.0 ng/mL [5.7-77.7 ng/mL] and 27.8 ng/mL [19.1-43.1
      ng/mL], respectively; p < 0.05). Cerebrospinal fluid level of ferritin was
      increased in traumatic brain injury patients at t2 and t1 versus controls (8.3
      ng/mL [<7.5-19.8 ng/mL] and 8.9 ng/mL [<7.5-26.7 ng/mL] vs <7.5 ng/mL below lower
      limit of detection, respectively; p < 0.05). Cerebrospinal fluid levels of
      soluble interleukin-2 receptor alpha in traumatic brain injury patients at t2 and
      t1 were not different versus controls. Multivariate regression revealed
      associations between high ferritin and age 4 years or younger, lower Glasgow Coma
      Scale score, abusive head trauma, and unfavorable Glasgow Outcome Scale score.
      CONCLUSIONS: Children with traumatic brain injury demonstrate evidence for
      macrophage activation after traumatic brain injury, and in terms of cerebrospinal
      fluid ferritin, this appears more prominent with young age, initial injury
      severity, abusive head trauma, and unfavorable outcome. Further study is needed
      to determine whether biomarkers of macrophage activation may be used to
      discriminate between aberrant and adaptive immune responses and whether
      inflammation represents a therapeutic target after traumatic brain injury.

PMID- 25850870
TI  - Surgical treatment of severe frontal bone fracture.
AB  - Craniofacial trauma can lead to several complications. The combined fractures of
      anterior and posterior walls of the frontal bone are almost always followed by
      lesions in nasofrontal orifices and disruption of nasofrontal ostia or ducts, a
      significant factor for the development of early and late complications after
      sinus fractures. This article reports a case of trauma patient, who underwent
      neurological evaluation and at first showed good general condition. Computed
      tomography noted fracture of the anterior and posterior walls of the frontal
      sinus and small foci of pneumocephalus in the cerebral cortex. The patient was
      monitored periodically and 9 days after trauma showed increased areas of
      pneumocephalus in prefrontal cortex, cerebrospinal fluid draining, and large dura
      mater lesion, with signs of necrosis and inflammation (meningitis). The necrotic
      tissues were removed, and dura mater was repaired through the approximation with
      resorbable wire polyglactin 910 5-0, oxidized cellulose application, and bonding
      with human fibrin sealant (fibrinogen, thrombin, and calcium chloride).
      Sinusectomy, frontal sinus, and nasofrontal duct obliteration with pedicled
      pericranium flap were performed. Tomographically, a reanatomization was noted in
      frontal region, and a 12-month follow-up showed no complication. The use of
      fibrin glue to repair dura mater lacerations, as well as the pedicle pericranium
      flap for frontal sinus and nasofrontal duct obliteration, is an efficient method
      for treating fractures of the frontal bone. 

PMID- 25850871
TI  - The importance of histopathologic analysis of pericoronal follicles for the early
      identification of ameloblastomas.
AB  - The objective of this study was to discuss the importance of performing
      histopathological examination of pericoronal follicles as a routine procedure, so
      as to enable the early identification of odontogenic lesions. We describe two
      clinical cases with histopathological diagnoses of ameloblastomas who did not
      show clinical or radiographic signs of disease before microscopic examination. 

PMID- 25850872
TI  - Giant nasal septal osteoma arising from perpendicular lamina of the ethmoid bone.

PMID- 25850873
TI  - Pediatric craniofacial pseudoaneurysm with a variable history of antecedent
      trauma.
AB  - A pseudoaneurysm (PA) is a vascular lesion occurring along an artery most often
      associated with previous trauma. It presents clinically as a compressible,
      pulsatile mass, which can be painful, growing, and associated with headaches. We
      report a series of 4 pediatric patients referred for management of a "cyst" who
      had superficial craniofacial PAs arising in a variety of different locations with
      a variable history of antecedent trauma.This is an institutional review board
      approved study of 4 consecutive patients presenting to the pediatric plastic
      surgery division with a diagnosis of PA between July 2012 and November 2013.The
      patients were initially referred for management of cyst. Each presented with
      compressible, pulsatile masses arising in varying locations along the superficial
      temporal or occipital arteries of the face and scalp. Three of the patients did
      not have a history of recent previous trauma. In the patients without history of
      trauma, further workup with duplex ultrasound was performed. In cases where the
      entire course of the artery could not be visualized by ultrasound, magnetic
      resonance angiography was performed to rule out an intracranial source of the
      lesion. Three lesions were excised with pathologic confirmation of the diagnosis
      of PA. All masses and associated symptoms resolved after the
      excision.Craniofacial PAs can occur in the pediatric population with a variable
      history of antecedent trauma. Awareness of this clinical phenomenon can help
      guide proper diagnosis for planning of safe, effective treatment. Surgical
      excision provides a safe, aesthetic result. 

PMID- 25850874
TI  - Predictive variables derived from panoramic radiographs for impacted maxillary
      cuspids treated with easy cuspid system.
AB  - The aim of the current study was to find, by means of panoramic radiographs, a
      viable statistical method to forecast the duration of orthodontic traction of
      impacted maxillary cuspids. The treatment sample consisted of 51 palatal impacted
      cuspids (19 unilateral and 32 bilateral) in 35 patients (aged between 10.5 and
      17.5 y) with a cervical vertebral maturation between cervical stage 1 and 4. Each
      patient underwent the same combined surgical-orthodontic technique. Anamnestic
      data as well as pretreatment panoramic radiograph and cephalogram with European
      Board of Orthodontics analysis were recorded for each case. Eight radiographic
      indicators were derived from panoramic films to define the reliable position of
      the impacted cuspid. Multiple regression analysis was used. All cuspids were
      successfully treated with an average traction time of 99 days (range, 33-188 d).
      The pretreatment radiographic features assessed on the panoramic radiographs did
      not significantly affect the duration of traction. The formula based on alpha
      angle, d1 distance, and S sector forecasted an average traction time of 123 days
      (range, 63-210 d), which is longer than the real time. No relevant correlations
      were found between orthodontic traction time and pretreatment radiograph
      parameters derived from panoramic film at the beginning of the treatment. The
      classic formula elaborated by Crescini could not be applied to the patients of
      this study, who were treated with the Easy Cuspid method.

PMID- 25850875
TI  - A new operative open-wings technique to correct the frontoforehead unit in
      metopic synostosis.
AB  - The technology adoption and creation of a multidisciplinary team have helped to
      overcome the complexity associated. Craniofacial surgery has thus emerged from
      the valuable contributions of neurosurgery, maxillofacial surgery, plastic
      surgery, eyes, nose, and throat as well as head and neck surgery. A patient with
      trigonocephaly may present a prominent "keel" forehead, accompanied by recession
      of the lateral orbit rims, hypotelorism, and constriction of the anterior frontal
      fossa when the metopic suture fuses before 6 months of age. In a period between
      2007 and 2011, in the Salesi Children's Hospital, were treated for nonsyndromic
      variety of metopic synostosis 11 infants; their ages ranged from 6 months to 9
      months, and 7 were males and 4 females. The most important aims of our new
      surgical technique are the achievement of symmetry as well as normal proportion
      and reconstruction of the frontoforehead unit but remaining in a very
      conservative treatment. The morphology and position of the supraorbital ridge
      lateral orbital rim region are key elements of upper facial esthetics. This new
      "open-wings" technique for the reconfiguration of the bilateral emisupraorbital
      bar requires a midline incomplete osteotomy that involves only the internal
      cortex of the frontonasal region. Hence, both lateral orbital walls are bent
      inwardly and tilting forward, as in computed tomographic scan planning, with a
      greenstick fracture pivoting on the preserved medial frontonasal region. This
      open-wings conservative technique allows the avoidance of the most important
      complication that may result in the traditional way such as dead space in the
      anterior cranial fossa, infections, and blood loss but with an achievement of
      satisfactory craniofacial form and aesthetic result.

PMID- 25850876
TI  - The application of an ultrasonic bone aspirator for septoturbinoplasty.
AB  - OBJECTIVE: The objectives of this study were to introduce the use of an
      ultrasonic bone aspirator (UBA; SONOPET [Mutoh Co, Ltd, Tokyo, Japan]) for
      septoturbinoplasty and to evaluate the efficacy and usefulness of this surgical
      procedure. DESIGN: This was a retrospective chart review. SETTING: This study was
      performed at a university medical center. METHODS: Of the 53 patients who
      underwent septoturbinoplasty from July to October 2013, 30 were operated on using
      a UBA and were enrolled in this study. Patients were followed for more than 6
      months after surgery. Patterns of septal deviation and surgical results and
      complications were investigated by paranasal sinus computed tomography scans,
      nasal endoscopy, and acoustic rhinometry. Improvement of symptoms was measured
      using the Nasal Obstruction Symptom Evaluation scale. RESULTS: Patterns of bony
      septal deviation were classified as follows: localized septal bony spur or crest
      (n = 7), basal bony septal deviation (n = 9), posterior bony septal deviation (n
      = 8), bony spur with basal part deviation (n = 5), and basal and posterior bony
      septal deviation (n = 1).Twenty-six patients underwent septoplasty with bilateral
      inferior turbinate reduction surgery using either a microdebrider (n = 10) or a
      microdebrider with UBA (n = 16). Four patients underwent septoplasty with
      unilateral turbinate reduction surgery using a microdebrider and UBA. Based on
      nasal endoscopic findings after surgery, 24 patients had a straight septum,
      whereas 6 exhibited minimal remaining curvature. Subjective symptoms of nasal
      obstruction evaluated using the visual analog scale and the Nasal Obstruction
      Symptom Evaluation scale were improved in all patients. Surgery using a UBA
      increased minimal cross-sectional area and nasal volume change in patients. There
      were no significant complications related to UBA use such as saddle nose,
      bleeding, or septal perforation. CONCLUSIONS: Application of a UBA for septo
      turbinate surgery is an easy, safe, and effective method that reduces the
      occurrence of common complications, such as septal perforation, delayed healing,
      infection, and bleeding. In addition, the UBA produces minimal thermal and
      mechanical injury to surrounding tissue and enables precise and incremental bone
      removal with continuous irrigation and suction. This tool allows for easy
      sculpting and reduction of bony architecture of the nasal cavity.

PMID- 25850877
TI  - Simple resolution with maxillary o-ring attachment overdenture.

PMID- 25850878
TI  - Myiasis in elderly involving oral and nasal cavities-diagnosis and treatment.

PMID- 25850879
TI  - Examining the Time to Therapeutic Effect of Pregabalin in Spinal Cord Injury
      Patients With Neuropathic Pain.
AB  - PURPOSE: In 2 large-scale, placebo-controlled trials, pregabalin improved both
      pain and pain-related sleep interference in patients with neuropathic pain due to
      spinal cord injury (SCI). In both trials, pregabalin found statistically
      significant improvement compared with placebo after 1 week of treatment. However,
      the effects of pregabalin in the days immediately after initiation of treatment
      are unknown. The purpose of the present analysis was to determine timing of
      pregabalin's therapeutic effect in the days after initiation of treatment.
      METHODS: Data were derived from 2 trials of pregabalin in patients with SCI
      related neuropathic pain. Each day patients rated severity of pain and pain
      related sleep interference over the past 24 hours on a scale from 0 to 10, with
      higher scores indicating greater severity. To quantify timing of therapeutic
      effect, we compared (pregabalin [vs] placebo) daily average pain and pain-related
      sleep interference scores over the first 14 days of treatment. Significant
      improvement was defined as the first day, of >=2 consecutive days, that
      pregabalin significantly (P < 0.05) reduced mean scores compared with placebo. To
      further quantify timing of therapeutic effect, each treatment group was examined
      to determine the time required to achieve a >=1-point improvement in pain and
      pain-related sleep interference score among patients with a clinically meaningful
      and sustained response (>=30% improvement from baseline to end point) by using a
      time-to-event analysis method. Kaplan-Meier analyses were used to estimate the
      median (or 25th quartile) time (in days) required to achieve a >=1-point
      improvement, among these responders, in pain and pain-related sleep interference
      scores. Comparisons between pregabalin and placebo were made with a log-rank
      test. FINDINGS: In both trials, significant improvement of pain and pain-related
      sleep interference occurred within 2 days of initiating treatment with
      pregabalin. Among patients reporting a clinically meaningful and sustained
      response to treatment (patients with >=30% improvement from baseline to end
      point), the time to a >=1-point improvement of pain and pain-related sleep
      interference occurred significantly earlier among pregabalin-treated patients
      than among placebo-treated patients. Finally, the timing of pregabalin's effect
      on pain and pain-related sleep interference was unaffected by the use of
      concomitant medications that were allowed for treatment of neuropathic pain in
      both trials. IMPLICATIONS: Treatment with pregabalin results in rapid time to
      significant improvement in both pain and pain-related sleep interference in
      patients with neuropathic pain due to SCI. These findings should only be used as
      a guide to physicians and patients as to when clinical response to pregabalin may
      be expected.

PMID- 25850880
TI  - Finding Truth in a World Full of Spin: Myth-Busting in the Case of Sovaldi.
AB  - PURPOSE: Public discourse regarding the hepatitis C virus (HCV) drug Sovaldi(r)
      (sofosbuvir) has become inflamed, generating much heat but little light
      concerning the clinical, health economic, and quality-of-life merits of
      Sovaldi(r). The purpose of this article is to provide a factual basis for
      evaluating the claims regarding the benefits of Sovaldi(r) relative to its costs.
      METHODS: A comprehensive review was conducted of news stories highlighted in the
      daily updates of the electronic newsletters BIO SmartBrief, FiercePharma,
      FierceBiotech and BioCentury Extra published from November 1, 2013, through
      December 31, 2014, on the topics of the HCV market, Sovaldi(r), and other HCV
      therapeutics. Also reviewed were recent practice guidelines on the management of
      HCV infections, prescribing information on all HCV drugs approved by the US Food
      and Drug Administration, and health technology assessments of Sovaldi(r) and
      Harvoni(TM) (sofosbuvir/ledipasvir). FINDINGS: Sovaldi(r) and Harvoni(TM) have
      provided significant improvements in the treatment of HCV, with all-oral regimens
      and cure rates exceeding 90% in some populations of patients with HCV. Sovaldi(r)
      prevents significant health care resource utilization in patients who would
      otherwise develop cirrhosis and require a liver transplant; however, only a small
      proportion of patients with HCV develop cirrhosis, and fewer require liver
      transplants. Because it is not possible to identify those patients whose HCV will
      progress to severe liver disease, it would be necessary to treat a large number
      of patients with HCV to prevent disease progression in this subpopulation,
      resulting in a considerable loss to health plans even over a 20-year horizon. The
      claim that treating all patients with HCV with Sovaldi(r) would cost nearly as
      much as the current total US expenditure on all prescription drugs, while
      factually correct, is not a realistic scenario. Many patients with HCV will
      continue to go undiagnosed. In addition, the medical expense for those who are
      treated will be spread out over many years. However, the unexpectedly large, up
      front cost of covering these drugs has had a major impact on health plan budgets,
      resulting in losses for some plans. IMPLICATIONS: Sovaldi(r) represents an
      enormous advance in the care of some populations of HCV-infected patients, but
      also a major cost burden to health plans. As the first of a number of
      anticipated, paradigm-changing drugs to treat medical conditions affecting large
      patient populations, Sovaldi(r) should act as a wake-up call for all health care
      stakeholders to engage in a meaningful, fact-based discussion about managing the
      cost of innovative new drugs to balance the needs of drug manufacturers, health
      plans, providers, and, above all, patients.

PMID- 25850882
TI  - Evaluation of the anterior chamber angle in keratoconus and normal subjects.
AB  - PURPOSE: To evaluate the anterior chamber angle in keratoconus eyes by use of the
      VisanteTM OCT and OrbscanTM II. METHODS: Anterior chamber angle was measured with
      the VisanteTM OCT and OrbscanTM II in 52 subjects, 26 KC subjects and 26 age and
      control subjects. RESULTS: When comparing the nasal and temporal angles obtained
      with the two techniques no correlation was found (R(2) always below 0.01) in
      either the control subjects or in the KC subjects. Despite this, there was an
      overall statistically significant difference in mean anterior chamber angles
      (p<0.001) between VisanteTM OCT and OrbscanTM II. There was no statistical
      difference (p>0.05) between nasal and temporal anterior chamber angles when
      comparing controls and KC subjects with either of the two instruments. In
      general, the VisanteTM OCT gave a smaller estimate of the anterior chamber angle.
      CONCLUSION: The values from the VisanteTM OCT and OrbscanTM II cannot be
      interchanged since the difference in measurement of the anterior chamber angle
      was significantly different between the two instruments.

PMID- 25850883
TI  - Dehydrocostus lactone suppressed the proliferation, migration, and invasion of
      colorectal carcinoma through the downregulation of eIF4E expression.
AB  - Dehydrocostus lactone (DHC) is the main active ingredient extracted from a
      traditional Chinese medicine called Radix Aucklandiael. A few studies recently
      showed that DHC has anticancer potential. However, no reports exist as yet on the
      effects of DHC on colorectal carcinoma (CRC). This study aimed to determine
      whether and how DHC functions in CRC cells. After treatment with DHC, both Lovo
      and SW480 cells were significantly inhibited in their proliferation, cell cycle
      progression, migration, and invasion abilities in a dose-dependent and/or
      treatment time-dependent manner. Also, DHC significantly increased the apoptosis
      rate of SW480 cells, but not Lovo cells. The expression of eukaryotic translation
      initiation factor 4E (eIF4E), which was originally highly expressed in both
      cells, was significantly decreased by DHC. The inhibition of proliferation,
      migration, and invasion was significantly attenuated by the ectopic transfection
      of eIF4E, and was promoted by the knockdown of eIF4E in Lovo cells. To the best
      of our knowledge, this is the first time it has been shown that DHC suppressed
      the proliferation, cell cycle progression, antiapoptosis, and migration and
      invasion capabilities of CRC cells by the downregulation of eIF4E expression. In
      terms of the overexpression of eIF4E in many cancers, it was speculated that DHC
      might also play an anticancerous role by suppressing eIF4E expression. This
      discovery could lay the foundations for advancing our understanding of the
      anticancerous mechanism of DHC and developing DHC into a novel and effective
      natural anticancer therapeutic. 

PMID- 25850881
TI  - A Randomized, Multicenter, Double-blind, Placebo-controlled, 3 * 3 Factorial
      Design, Phase II Study to Evaluate the Efficacy and Safety of the Combination of
      Fimasartan/Amlodipine in Patients With Essential Hypertension.
AB  - PURPOSE: The objective of this study was to evaluate the efficacy and safety of a
      fimasartan/amlodipine combination in patients with hypertension and to determine
      the optimal composition for a future single-pill combination formulation.
      METHODS: This Phase II study was conducted by using a randomized, multicenter,
      double-blind, placebo-controlled, 3 * 3 factorial design. After a 2-week placebo
      run-in period, eligible hypertensive patients (with a sitting diastolic blood
      pressure [SiDBP] between 90 and 114 mm Hg) were randomized to treatment. They
      received single or combined administration of fimasartan at 3 doses (0, 30, and
      60 mg) and amlodipine at 3 doses (0, 5, and 10 mg) for 8 weeks. The primary
      efficacy end point was the change in SiDBP from baseline and at week 8; secondary
      end points included the change in SiDBP from baseline and at week 4 and the
      changes in sitting systolic blood pressure from baseline and at weeks 4 and 8.
      Treatment-emergent adverse events (AEs) were also assessed. FINDINGS: 420 Korean
      patients with mild to moderate hypertension were randomly allocated to the 9
      groups. Mean (SD) SiDBP changes in each group after 8 weeks were as follows:
      placebo, -6.0 (8.5) mm Hg; amlodipine 5 mg, -10.6 (9.2) mm Hg; amlodipine 10 mg, 
      15.9 (7.2) mm Hg; fimasartan 30 mg, -10.1 (9.1) mm Hg; fimasartan 60 mg, -13.0
      (10.0) mm Hg; fimasartan 30 mg/amlodipine 5 mg, -16.2 (8.5) mm Hg; fimasartan 30
      mg/amlodipine 10 mg, -19.5 (7.5) mm Hg; fimasartan 60 mg/amlodipine 5 mg, -16.6
      (6.9) mm Hg; and fimasartan 60 mg/amlodipine 10 mg, -21.5 (8.3) mm Hg. All
      treatment groups produced significantly greater reductions in blood pressure
      compared with the placebo group. In addition, all combination treatment groups
      had superior reductions in blood pressure compared with the monotherapy groups.
      In the combination treatment groups, doubling fimasartan dose in the given dose
      of amlodipine did not show further BP reduction, whereas doubling amlodipine dose
      showed significantly further BP reduction in the given dose of fimasartan. During
      the study period, 75 (17.9%) of 419 patients experienced 110 AEs. Ninety-five AEs
      were mild, 9 were moderate, and 6 were severe in intensity. Eight patients
      discontinued the study due to AEs. There was no significant difference in
      incidence of AEs among groups (P = 0.0884). The most common AE was headache (12
      patients [2.9%]), followed by dizziness (11 patients [2.6%]) and elevated blood
      creatine phosphokinase levels (6 patients [1.4%]). IMPLICATIONS: Fimasartan
      combined with amlodipine produced superior blood pressure reductions and low
      levels of AEs compared with either monotherapy. Therefore, a single-pill
      combination with fimasartan 60 mg/amlodipine 10 mg will be developed.
      ClinicalTrials.gov: NCT01518998.

PMID- 25850884
TI  - Neutralization of the CD95 ligand by APG101 inhibits invasion of glioma cells in
      vitro.
AB  - Glioblastoma is a disease characterized by rapid invasive tumour growth. Studies
      on the proapoptotic CD95/CD95L signalling pathway recently suggested a
      significant contribution of CD95 signalling towards the high degree of motility
      in glioma cells. Apogenix has developed APG101, a clinical phase II compound
      designed to bind and neutralize CD95L, and thus to interfere with CD95/CD95L
      based signalling. APG101 has shown clinical efficacy in a controlled randomized
      phase II trial in patients with recurrent glioma. Because APG101 is not cytotoxic
      to tumour cells in vitro, we postulated that the anti-invasive function of APG101
      is the main mechanism of action for this compound. Using three-dimensional
      spheroid invasion assays in vitro and in murine brain tissue cultures, we found
      that knockdown of endogenous CD95L reduced the invasive phenotype in our two
      glioblastoma model cell lines U87-MG and U251-MG. Invasion was restored in CD95L
      knockdown cells upon the addition of soluble recombinant CD95L and this effect
      was inhibited by APG101. We conclude that CD95L from autocrine and paracrine
      sources contributes towards the invasive phenotype of glioblastoma cells and that
      APG101 acts as a suppressor of proinvasive signalling by the CD95/CD95L pathway
      in glioblastoma. 

PMID- 25850885
TI  - Gum chewing and gastrointestinal function following caesarean delivery: a
      systematic review and meta-analysis.
AB  - AIMS AND OBJECTIVES: The aims of this systematic review and meta-analysis were to
      summarise current knowledge regarding gum chewing intervention for activation of
      the gastrointestinal (GI) system following caesarean delivery. BACKGROUND: GI
      symptoms such as nausea, vomiting and defecatory difficulties are bothersome for
      women following a caesarean delivery. There is category A recommendation to not
      withhold oral intake postoperatively. However, current practice guidelines vary
      widely on time to initiate oral feeding post caesarean delivery, and additional
      research is needed. Gum chewing has been shown to stimulate the GI system in
      other postoperative patient populations. DESIGN: A systematic review and meta
      analysis. METHODS: An electronic review was undertaken using the following
      resources: PubMed (Medline), CINAHL, EMBASE and ClinicalTrials.gov databases. Key
      words used in various combinations included cesarean section; cesarean delivery;
      postoperative chewing gum; bowel movement; bowel function and complications.
      RESULTS: A total of 171 articles were found of which 166 were excluded: 157 were
      duplicates and the remainder did not meet the inclusion criteria. Five randomised
      control trials were included in the meta-analysis, focusing on gum chewing as an
      intervention as compared with a nongum chewing intervention, with a total of 846
      participants. Compared with the nongum chewing group, gum chewing showed a
      beneficial impact on the major outcomes of digestive system activation, including
      bowel sound, gas passage and defecation. CONCLUSIONS: This meta-analysis supports
      the effectiveness of gum chewing post caesarean delivery as a
      noninvasive/nonpharmacological intervention for reactivation of bowel movement.
      RELEVANCE TO CLINICAL PRACTICE: Gum chewing in the immediate postoperative period
      following caesarean delivery may provide a socially acceptable, low-cost and safe
      intervention to reduce postcaesarean delivery GI complications and restore GI
      function.

PMID- 25850886
TI  - Historical thinking in clinical medicine: lessons from R.G. Collingwood's
      philosophy of history.
AB  - The aim of this article is to create a space for historical thinking in medical
      practice. To this end, we draw on the ideas of R.G. Collingwood (1889-1943), the
      renowned British philosopher of history, and explore the implications of his
      philosophy for clinical medicine. We show how Collingwood's philosophy provides a
      compelling argument for the re-centring of medical practice around the patient
      history as a means of restoring to the clinical encounter the human meaning that
      is too often lost in modern medicine. Furthermore, we examine how Collingwood's
      historical thinking offers a patient-centred epistemology and a more pluralistic
      concept of evidence that includes the qualitative, narrative evidence necessary
      for human understanding. We suggest that clinical medicine can benefit from
      Collingwood's historical thinking, and, more generally, illustrates how a
      philosophy of medicine that draws on diverse sources from the humanities offers a
      richer, more empathetic clinical practice.

PMID- 25850887
TI  - [Lingual neuromas in childhood as clue for diagnosis of the MEN 2B syndrome].

PMID- 25850888
TI  - Modeling universal dynamics of cell spreading on elastic substrates.
AB  - A three-dimensional (3D) multiscale moving contact line model is combined with a
      soft matter cell model to study the universal dynamics of cell spreading over
      elastic substrates. We have studied both the early stage and the late stage cell
      spreading by taking into account the actin tension effect. In this work, the cell
      is modeled as an active nematic droplet, and the substrate is modeled as a St.
      Venant Kirchhoff elastic medium. A complete 3D simulation of cell spreading has
      been carried out. The simulation results show that the spreading area versus
      spreading time at different stages obeys specific power laws, which is in good
      agreement with experimental data and theoretical prediction reported in the
      literature. Moreover, the simulation results show that the substrate elasticity
      may affect force dipole distribution inside the cell. The advantage of this
      approach is that it combines the hydrodynamics of actin retrograde flow with
      moving contact line model so that it can naturally include actin tension effect
      resulting from actin polymerization and actomyosin contraction, and thus it might
      be capable of simulating complex cellular scale phenomenon, such as cell
      spreading or even crawling. 

PMID- 25850889
TI  - Value of CT findings to predict surgical ischemia in small bowel obstruction: A
      systematic review and meta-analysis.
AB  - PURPOSE: Our aim was to assess the diagnostic performance in determining
      strangulation in small bowel obstruction (SBO) for five CT findings commonly
      considered in published small bowel obstruction (SBO) management guidelines.
      MATERIALS AND METHODS: Medical databases were searched for "bowel obstruction",
      "computed tomography", "strangulation", and related terms. Two reviewers
      independently selected articles for CT findings investigated with surgical or
      histological reference standards for strangulation. Bivariate random-effects meta
      analytical methods were used. RESULTS: A total of 768 patients, including 205
      with strangulation from nine studies, were evaluated. The reduced bowel wall
      enhancement CT sign had the highest specificity (95 %, CI 75-99), with a positive
      LR of 11.07 (2.27-53.88) and DOR of 22.86 (4.99-104.61). The mesenteric fluid
      sign had the highest sensitivity (89 %, CI 75-96) with a negative LR of 0.16
      (0.07-0.39) and a DOR of 13.9 (5.73-33.75). The bowel wall thickness had a
      sensitivity of 48 % (CI 41-54), a specificity of 83 % (CI 74-89), a positive LR
      of 2.84 (1.83-4.41) and a negative LR of 0.62 (0.53-0.72). The other CT findings
      had lower diagnostic performance. CONCLUSION: Two CT findings should be used in
      clinical practice: reduced enhanced bowel wall is highly predictive of ischemia,
      and absence of mesenteric fluid is a reliable finding to rule out strangulation.
      KEY POINTS: * Reduced bowel wall enhancement on CT increases the probability of
      strangulation 11-fold. * Absence of mesenteric fluid on CT decreases the
      probability of strangulation 6-fold. * The clinical reliability of other CT signs
      is doubtful for predicting strangulation.

PMID- 25850890
TI  - Effect of TIPS placement on portal and splanchnic arterial blood flow in 4
      dimensional flow MRI.
AB  - OBJECTIVES: To assess changes in portal and splanchnic arterial haemodynamics in
      patients undergoing transjugular intrahepatic portosystemic shunt (TIPS) using
      four-dimensional (4D) flow MRI, a non-invasive, non-contrast imaging technique.
      METHODS: Eleven patients undergoing TIPS implantation were enrolled. K-t GRAPPA
      accelerated non-contrast 4D flow MRI of the liver vasculature was applied with
      acceleration factor R = 5 at 3Tesla. Flow analysis included three-dimensional
      (3D) blood flow visualization using time-resolved 3D particle traces and semi
      quantitative flow pattern grading. Quantitative evaluation entailed peak
      velocities and net flows throughout the arterial and portal venous (PV) systems.
      MRI measurements were taken within 24 h before and 4 weeks after TIPS placement.
      RESULTS: Three-dimensional flow visualization with 4D flow MRI revealed good
      image quality with minor limitations in PV flow. Quantitative analysis revealed a
      significant increase in PV flow (562 +/- 373 ml/min before vs. 1831 +/- 965
      ml/min after TIPS), in the hepatic artery (176 +/- 132 ml/min vs. 354 +/- 140
      ml/min) and combined flow in splenic and superior mesenteric arteries (770 ml/min
      vs. 1064 ml/min). Shunt-flow assessment demonstrated stenoses in two patients
      confirmed and treated at TIPS revision. CONCLUSIONS: Four-dimensional flow MRI
      might have the potential to give new information about the effect of TIPS
      placement on hepatic perfusion. It may explain some unexpected findings in
      clinical observation studies. KEY POINTS: * 4D flow MRI, a non-invasive, non
      contrast imaging technique, is feasible after TIPS. * Provides visualization and
      quantification of hepatic arterial, portal venous, collateral and TIPS
      haemodynamics. * Better understanding of liver blood flow changes after TIPS and
      patient management.

PMID- 25850891
TI  - Optimizing computed tomography pulmonary angiography using right atrium bolus
      monitoring combined with spontaneous respiration.
AB  - OBJECTIVES: CT pulmonary angiography (CTPA) aims to provide pulmonary arterial
      opacification in the absence of significant pulmonary venous filling. This
      requires accurate timing of the imaging acquisition to ensure synchronization
      with the peak pulmonary artery contrast concentration. This study was designed to
      test the utility of right atrium (RA) monitoring in ensuring optimal timing of
      CTPA acquisition. METHODS: Sixty patients referred for CTPA were divided into two
      groups. Group A (n = 30): CTPA was performed using bolus triggering from the
      pulmonary trunk, suspended respiration and 70 ml of contrast agent (CA). Group B
      (n = 30): CTPA image acquisition was triggered using RA monitoring with
      spontaneous respiration and 40 ml of CA. Image quality was compared. RESULTS:
      Subjective image quality, average CT values of pulmonary arteries and density
      difference between artery and vein pairs were significantly higher whereas CT
      values of pulmonary veins were significantly lower in group B (all P < 0.05).
      There was no significant difference between the groups in the proportion of
      subjects where sixth grade pulmonary arteries were opacified (P > 0.05).
      CONCLUSIONS: RA monitoring combined with spontaneous respiration to trigger image
      acquisition in CTPA produces optimal contrast enhancement in pulmonary arterial
      structures with minimal venous filling even with reduced doses of CA. KEY POINTS:
      * Bolus tracking (BT) with pulmonary trunk monitoring is widely used in CTPA. *
      Pulmonary venous contamination is a disadvantage of BT due to transition delay
      time. * Right atrium monitoring with spontaneous respiration can optimize CTPA. *
      It produces optimal contrast enhancement in pulmonary arteries with minimal
      venous filling. * The contrast dose was significantly reduced.

PMID- 25850892
TI  - Interreader and inter-test agreement in assessing treatment response following
      transarterial embolization for hepatocellular carcinoma.
AB  - PURPOSE: To evaluate interreader and inter-test agreement in applying size- and
      necrosis-based response assessment criteria after transarterial embolization
      (TAE) for hepatocellular carcinoma (HCC), applying two different methods of
      European Association for the Study of the Liver (EASL) criteria. METHODS: Seventy
      four patients (median age, 67 years) from a prospectively accrued study
      population were included in this retrospective study. Four radiologists
      independently evaluated CT data at 2-3 (1st follow-up, FU) and 10-12 (2nd FU)
      weeks after TAE and assessed treatment response using size-based (WHO, RECIST)
      and necrosis-based (mRECIST, EASL) criteria. Enhancing tissue was bidimensionally
      measured (EASLmeas) and also visually estimated (EASLest). Interreader and inter
      test agreements were assessed using intraclass correlation coefficient (ICC) and
      kappa statistics. RESULTS: Interreader agreement for all response assessment
      methods ranged from moderate to substantial (kappa = 0.578-0.700) at 1st FU and
      was substantial (kappa = 0.716-0.780) at 2nd FU. Inter-test agreement was
      substantial between WHO and RECIST (kappa = 0.610-0.799, 1st FU; kappa = 0.655
      0.782, 2nd FU) and excellent between EASLmeas and EASLest (kappa = 0.899-0.918,
      1st FU; kappa = 0.843-0.877, 2nd FU). CONCLUSION: Size- and necrosis-based
      criteria both show moderate to excellent interreader agreement in evaluating
      treatment response after TAE for HCC. Inter-test agreement regarding EASLmeas and
      EASLest was excellent, suggesting that either may be used. KEY POINTS: * Applying
      EASL criteria, visual estimation and bidimensional measurements show comparable
      interreader agreement. * EASL meas and EASL est show substantial interreader
      agreement for treatment response in HCC. * Agreement was excellent for EASL meas
      and EASL est after TAE of HCC. * Visual estimation of enhancement is adequate to
      assess treatment response of HCC.

PMID- 25850893
TI  - The Complex Interaction Between Methamphetamine Abuse and HIV-1 Pathogenesis.
AB  - The global HIV/AIDS pandemic has claimed the lives of an estimated 35 million
      people. A significant barrier for combating this global pandemic is substance use
      since it is associated with HIV transmission, delayed diagnosis/initiation of
      therapy, and poor adherence to therapy. Clinical studies also suggest a link
      between substance use and HIV-disease progression/AIDS-associated mortality.
      Methamphetamine (METH) use is one of the fastest-growing substance use problems
      in the world. METH use enhances high-risk sexual behaviors, therefore increases
      the likelihood of HIV-1 acquisition. METH use is also associated with higher
      viral loads, immune dysfunction, and antiretroviral resistance. Moreover, METH
      use has also been correlated with rapid progression to AIDS. However, direct
      effects of METH on HIV-1 disease progression remains poorly understood because
      use of METH and other illicit drugs is often associated with reduced/non
      adherence to ART. Nevertheless, in vitro studies demonstrate that METH increases
      HIV-1 replication in cell cultures and animal models. Thus, it has been proposed
      that METH's potentiating effects on HIV-1 replication may in part contribute to
      the worsening of HIV-1 pathogenesis. However, our recent data demonstrate that
      METH at physiologically relevant concentrations has no effect and at higher
      concentrations inhibits HIV-1 replication in CD4+ T cells. Thus, the goal of this
      review is to systematically examine the published literature to better understand
      the complex interaction between METH abuse and HIV-1 disease progression. 

PMID- 25850895
TI  - Dramatic Improvement of Chronic Inflammatory Demyelinating Polyneuropathy Through
      Tenofovir Treatment in a Patient Infected with Hepatitis B Virus.

PMID- 25850894
TI  - Neurochemical Metabolomics Reveals Disruption to Sphingolipid Metabolism
      Following Chronic Haloperidol Administration.
AB  - Haloperidol is an effective antipsychotic drug for treatment of schizophrenia,
      but prolonged use can lead to debilitating side effects. To better understand the
      effects of long-term administration, we measured global metabolic changes in
      mouse brain following 3 mg/kg/day haloperidol for 28 days. These conditions lead
      to movement-related side effects in mice akin to those observed in patients after
      prolonged use. Brain tissue was collected following microwave tissue fixation to
      arrest metabolism and extracted metabolites were assessed using both liquid and
      gas chromatography mass spectrometry (MS). Over 300 unique compounds were
      identified across MS platforms. Haloperidol was found to be present in all test
      samples and not in controls, indicating experimental validity. Twenty-one
      compounds differed significantly between test and control groups at the p < 0.05
      level. Top compounds were robust to analytical method, also being identified via
      partial least squares discriminant analysis. Four compounds (sphinganine, N
      acetylornithine, leucine and adenosine diphosphate) survived correction for
      multiple testing in a non-parametric analysis using false discovery rate
      threshold < 0.1. Pathway analysis of nominally significant compounds (p < 0.05)
      revealed significant findings for sphingolipid metabolism (p = 0.015) and protein
      biosynthesis (p = 0.024). Altered sphingolipid metabolism is suggestive of
      disruptions to myelin. This interpretation is supported by our observation of
      elevated N-acetyl-aspartyl-glutamate in the haloperidol-treated mice (p = 0.004),
      a marker previously associated with demyelination. This study further
      demonstrates the utility of murine neurochemical metabolomics as a method to
      advance understanding of CNS drug effects.

PMID- 25850896
TI  - An intramolecular crossed-benzoin reaction based KCN fluorescent probe in aqueous
      and biological environments.
AB  - A turn-on fluorescent probe was designed for selective cyanide anion sensing in
      aqueous and biological environments. The probe underwent an intramolecular
      crossed-benzoin reaction in the presence of KCN to expel the fluorophore
      resorufin. This probe was sensitive to KCN concentrations as low as 4 nM in
      aqueous media. 

PMID- 25850897
TI  - The Role of Chronic Disease, Obesity, and Improved Treatment and Detection in
      Accounting for the Rise in Healthcare Spending Between 1987 and 2011.
AB  - BACKGROUND: To curb rising healthcare expenditures in the U.S.A., the factors
      underlying this growth must be well understood. OBJECTIVE: We aim to explore how
      chronic disease prevalence, obesity, and improved disease detection and treatment
      rates contributed to the growth in health spending in the U.S.A. between 1987 and
      2011. METHODS: We use spending decomposition equations to estimate the portion of
      spending growth attributable to prevalence increases, rising treatment costs, and
      population growth, respectively. We use two-part models to estimate the portion
      of prevalence-related spending that is potentially due to obesity. We examine
      changing diagnosis and treatment rates to assess how much of the growth in
      spending might be desirable. RESULTS: We find that the share of total healthcare
      spending associated with the treatment of chronic disease has risen dramatically
      from 1987-2011. In particular, we estimate that 77.6% of healthcare spending
      growth is attributable to patients with four or more chronic conditions. We find
      that rising obesity levels may explain between 11.4 and 23.5% of the increase in
      healthcare expenditure for several specific chronic conditions. Diagnosis and
      treatment rates for chronic disease are improving. CONCLUSIONS: Individuals with
      multiple chronic conditions are disproportionately responsible for rising
      healthcare expenditure. Much of spending growth associated with rising rates of
      chronic disease can be linked to rising obesity rates. Though much of the growth
      in spending is generally considered undesirable, disease detection and treatment
      rates are also rising, suggesting that at least some of the recent growth in
      healthcare expenditure may be beneficial.

PMID- 25850898
TI  - Human exposure to methylmercury from crayfish (Procambarus clarkii) in China.
AB  - Methylmercury (MeHg) accumulation in aquatic food raises global concerns about
      human exposure to MeHg. Crayfish is the world's third largest farmed crustacean
      species and a favorite aquatic food in many countries. However, human health
      hazard due to MeHg exposure via crayfish consumption is unclear, partly because
      appropriate survey data are lacking. We report on mercury concentrations and
      speciation in edible tail muscle of crayfish collected from restaurants in 23
      Chinese cities. On average, MeHg constituted 99.1 % of mercury in tail muscle,
      and MeHg concentrations were comparable with those reported for fish in China.
      Variation in MeHg concentrations was not attributable to broad geographic region
      (i.e., provinces) or tail length. For different populations, potential health
      risk (characterized by hazard quotient or HQ) of MeHg exposure through crayfish
      consumption depended largely on crayfish consumption rates. In particular, a
      health hazard (HQ > 1) was found for high-rate consumers (i.e., 95 %ile or
      higher) in some cities in the middle and lower reaches of the Yangtze River
      (MLYR), during the peak consumption season. Our results suggest that more
      attention should be paid to dietary MeHg intake via crayfish consumption in
      China, particularly for communities with high consumption in MLYR. 

PMID- 25850899
TI  - The Targeted Delivery of Interleukin 4 Inhibits Development of Endometriotic
      Lesions in a Mouse Model.
AB  - Endometriosis is caused by the displacement of endometrium outside the uterus
      contributing heavily to infertility and debilitating pelvic pain. Ectopic
      adhesion and growth are believed to occur under the influence of a favorable
      hormonal environment and immunological factors. The objective of this study is to
      analyze the effect of a targeted therapy with an antibody-based pharmacodelivery
      of interleukin 4 (F8-IL4) in a mouse model of experimentally induced
      endometriosis. Endometriosis-like lesions were induced in Balb/c mice. The
      animals were treated intravenously with F8-IL4 or with untargeted IL4 (KSF-IL4).
      Twelve days after disease induction, the lesions were isolated. A significant
      reduction in the number of total lesions/mouse and in the total volume of
      lesions/mouse was observed in mice treated with F8-IL4 compared to controls (P =
      .029 and P = .006, respectively), while no difference was found between KSF-IL4
      treated mice and their controls. Gene expression was evaluated by quantitative
      real-time polymerase chain reaction. Expression of genes involved in cell
      adhesion, extracellular matrix invasion, and neovascularization was significantly
      downregulated in F8-IL4-treated mice compared to their controls (integrin beta1:
      P = .02; metalloproteinase [MMP] 3: P = .02; MMP9: P = .04; vascular endothelial
      growth factor: P = .04). Gene expression of inflammatory cytokines (tumor
      necrosis factor alpha, IL1beta, IL1alpha, and IL6) did not vary in the ectopic
      lesions isolated from F8-IL4-treated mice compared to their controls.
      Immunohistochemistry demonstrated a significantly reduced expression of E
      cadherin and beta-catenin in the lesions of mice treated with F8-IL4. Our results
      show that the antibody-mediated targeted delivery of IL4 inhibits the development
      of endometriosis in a syngeneic mouse model by likely impairing adhesion,
      invasion, and vascularization of the ectopic endometrium. 

PMID- 25850900
TI  - Functional patterns of cytomegalovirus (CMV) pp65 and immediate early-1-specific
      CD8(+) T cells that are associated with protection from and control of CMV
      DNAemia after allogeneic stem cell transplantation.
AB  - BACKGROUND: The functional profile of cytomegalovirus (CMV)-specific CD8(+) T
      cells that associate with protection from and control of CMV DNAemia in
      allogeneic stem cell transplant (allo-SCT) recipients remains incompletely
      characterized. METHODS: We enumerated pp65 and immediate early (IE)-1-specific
      CD8(+) T cells expressing interferon-gamma, tumor necrosis factor-alpha, and
      CD107a, by flow cytometry in 94 patients at days +30 and +60 after allo-SCT.
      RESULTS: Fifty of 94 patients had CMV DNAemia within the first 100 days after
      transplant. CMV-specific CD8(+) T-cell responses (of any functional type) were
      more likely to be detected in patients who did not display CMV DNAemia than in
      those who did (P = 0.04). Qualitatively, no major differences in the functional
      signature of CMV-specific CD8(+) T cells were noted between patients who had or
      did not have CMV DNAemia. Patients displaying levels of polyfunctional CD8(+) T
      cells at day +30 >0.30 cell/MUL had a lower risk of CMV DNAemia (positive
      predictive value 76%, and negative predictive value 43%). CONCLUSION: The
      presence of polyfunctional CD8(+) T cells (either expressing CD107a or not) was
      associated with lower levels of CMV replication, and higher frequency of self
      resolved episodes. The data reported further clarify the role of polyfunctional
      CD8(+) T cells in control of CMV DNAemia in allo-SCT recipients.

PMID- 25850901
TI  - High expression of cytochrome b 5 reductase isoform 3/cytochrome b 5 system in
      the cerebellum and pyramidal neurons of adult rat brain.
AB  - Cytochrome b 5 reductase (Cb 5R) and cytochrome b 5 (Cb 5) form an enzymatic
      redox system that plays many roles in mammalian cells. In the last 15 years, it
      has been proposed that this system is involved in the recycling of ascorbate, a
      vital antioxidant molecule in the brain and that its deregulation can lead to the
      production of reactive oxygen species that play a major role in oxidative-induced
      neuronal death. In this work, we have performed a regional and cellular
      distribution study of the expression of this redox system in adult rat brain by
      anti-Cb 5R isoform 3 and anti-Cb 5 antibodies. We found high expression levels in
      cerebellar cortex, labeling heavily granule neurons and Purkinje cells, and in
      structures such as the fastigial, interposed and dentate cerebellar nuclei. A
      large part of Cb 5R isoform 3 in the cerebellum cortex was regionalized in close
      proximity to the lipid raft-like nanodomains, labeled with cholera toxin B, as we
      have shown by fluorescence resonance energy transfer imaging. In addition,
      vestibular, reticular and motor nuclei located at the brain stem level and
      pyramidal neurons of somatomotor areas of the brain cortex and of the hippocampus
      have been also found to display high expression levels of these proteins. All
      these results point out the enrichment of Cb 5R isoform 3/Cb 5 system in neuronal
      cells and structures of the cerebellum and brain stem whose functional impairment
      can account for neurological deficits reported in type II congenital
      methemoglobinemia, as well as in brain areas highly prone to undergo oxidative
      stress-induced neurodegeneration.

PMID- 25850902
TI  - Alcohol and lithium have opposing effects on the period and phase of the
      behavioral free-running activity rhythm.
AB  - Bipolar patients have a high prevalence of comorbid alcohol use and abuse
      disorders, while chronic alcohol drinking may increase the presence and severity
      of certain symptoms of bipolar disorder. As such, there may be many individuals
      that are prescribed lithium to alleviate the manic symptoms of bipolar disorder,
      but also drink alcohol concurrently. In addition, both alcoholics and individuals
      with bipolar disorder often exhibit disruptions to their sleep-wake cycles and
      other circadian rhythms. Interestingly, both ethanol and lithium are known to
      alter both the period and the phase of free-running rhythms in mammals. While
      lithium is known to lengthen the period, ethanol seems to shorten the period and
      attenuate the responses to acute light pulses. Therefore, the present study aimed
      to determine whether ethanol and lithium have opposing effects on the circadian
      pacemaker when administered together. C57BL/6J mice were provided drinking
      solutions containing lithium, alcohol, or both, and their free-running rhythms
      along with their response to photic phase shifts were investigated. Mice treated
      with lithium displayed period lengthening, which was almost completely negated
      when ethanol was added. Moreover, ethanol significantly attenuated light-induced
      phase delays while the addition of lithium partially restored this response.
      These results indicate that alcohol and lithium have opposing effects on
      behavioral circadian rhythms. Individuals with bipolar disorder who are
      prescribed lithium and who drink alcohol might be inadvertently altering their
      sleep and circadian cycles, which may exacerbate their symptoms.

PMID- 25850903
TI  - Physical Activity as an Intervention for Antenatal Depression: Rationale for
      Developing Tailored Exercise Programs for Pregnant Women with Depression.

PMID- 25850904
TI  - Ethnicity, deprivation and mortality due to 2009 pandemic influenza A(H1N1) in
      England during the 2009/2010 pandemic and the first post-pandemic season.
AB  - The relationship between risk of death following influenza A(H1N1)pdm09 infection
      and ethnicity and deprivation during the 2009/2010 pandemic period and the first
      post-pandemic season of 2010/2011 in England was examined. Poisson regression
      models were used to estimate the mortality risk, adjusted for age, gender, and
      place of residence. Those of non-White ethnicity experienced an increased
      mortality risk compared to White populations during the 2009/2010 pandemic
      [10.5/1000 vs. 6.0/1000 general population; adjusted risk ratio (RR) 1.84, 95%
      confidence interval (CI) 1.39-2.54] with the highest risk in those of Pakistani
      ethnicity. However, no significant difference between ethnicities was observed
      during the following 2010/2011 season. Persons living in areas with the highest
      level of deprivation had a significantly higher risk of death (RR 2.08, 95% CI
      1.49-2.91) compared to the lowest level for both periods. These results highlight
      the importance of rapid identification of groups at higher risk of severe disease
      in the early stages of future pandemics to enable the implementation of optimal
      prevention and control measures for vulnerable populations. 

PMID- 25850905
TI  - Periprosthetic BMD after cemented and uncemented total hip arthroplasty: a 10
      year follow-up study.
AB  - BACKGROUND AND PURPOSES: Insertion of a metallic implant into the femur changes
      bone loading conditions and results in remodeling of femoral bone. To quantify
      these changes in bone mineral density (BMD) after total hip arthroplasty, we
      monitored femoral bone with dual X-ray absorptiometry (DXA). MATERIALS AND
      METHODS: The periprosthetic bone mineral density was measured in seven Gruen
      zones at scheduled time intervals during a 10-year follow-up. A total of 38
      patients went through either cemented (n = 13) or uncemented arthroplasty (n =
      25). RESULTS: During the 1st post-operative year BMD decreased markedly in both
      groups mainly in the calcar area (Gruen zone 7); 21.9 % in the uncemented group
      (p < 0.005) and 26.1 % in the cemented group (p < 0.005). After that there was a
      slight continuous BMD loss in the proximal part of the femur and a slight
      increase in the distal part of femur, especially after uncemented THA. In the non
      operated control side, BMD showed only a slight decrease during the follow-up
      (0.9 %, p = 0.003). INTERPRETATION: The study shows that when a good prosthesis
      bone integration with or without cement is achieved, remodeling of the
      periprosthetic bone decreases after the 1st post-operative year and the bone loss
      reflects merely normal ageing.

PMID- 25850906
TI  - Ongoing Stent Thrombosis: Optical Coherence Tomography Findings.

PMID- 25850907
TI  - Amyloid and the cardiovascular system: A review of pathogenesis and pathology
      with clinical correlations.
AB  - The process of amyloidogenesis may complicate diverse disease states. It may be
      systemic and have serious clinical sequelae; in other circumstances, it is a
      localized phenomenon and functionally insignificant. In many cases its
      manifestations may be predictable, with knowledge of the responsible protein.
      Perhaps no organ system better exemplifies this than the cardiovascular one in
      which amyloid may form from precursor proteins as varied as immunoglobulin light
      chains, serum amyloid-A protein, transthyretin and its variants, atrial
      natriuretic factor, beta2-microglobulin, and others. This review describes the
      state of knowledge in relation to cardiovascular amyloidosis, with particular
      emphasis on what is currently known about the pathogenesis of the process and the
      related pathology of the various anatomic components of the cardiovascular
      system. 

PMID- 25850908
TI  - Association of prenatal closure of the foramen ovale and fetal parvovirus B19
      infection in hydrops fetalis.
AB  - Stenosis of the foramen ovale was found at autopsy in a preterm hydropic female
      who died 3 hours after birth. Subsequently, fetal infection by the human
      parvovirus B19 was diagnosed by serology collected at autopsy and by identifying
      the viral genome in both the placenta and autopsy liver by polymerase chain
      reaction. Morphologic findings at autopsy suggested that the disease was in a
      recovery phase. Prenatal closure of the foramen ovale, as an isolated lesion, is
      a recognized association of fetal hydrops because right-to-left cardiac shunting
      through the foramen is obligatory during fetal life. Parvovirus infection is also
      associated with fetal hydrops, the mechanism being congestive heart failure
      secondary to acute anemia. Coincidence in this case of both a cardiac and an
      infective cause of fetal hydrops suggests that the two putative causes are
      related. We suggest that an episode of fetal congestive heart failure (triggered
      in this case by anemia caused by fetal parvovirus infection) may initiate
      prenatal closure of a normally formed and previously patent foramen ovale. If
      this is true, the congenital anatomic anomaly would represent a cardiac
      deformation acquired during fetal life rather than a malformation dating from
      embryonic life. 

PMID- 25850909
TI  - The cardiovascular pathology of phospholipid antibodies: An illustrative case and
      review of the literature.
AB  - There is some confusion in the literature regarding the pathology associated with
      phospholipid antibodies. These antibodies, formed to a number of negatively
      charged phospholipids, are associated with an increased tendency to both arterial
      and venous thrombosis and embolism and may be manifest in a primary syndrome, a
      syndrome secondary to systemic lupus erythematosis, or as an isolated phenomenon,
      which may or may not be associated with thromboembolism. The pathogenesis of
      thrombosis in these syndromes has not yet been elucidated. Indeed it is not even
      clearly established that the antibodies have a pathogenic role, as opposed to
      existing as an epiphenomenon or arising secondary to some form of vascular
      damage. Clarification of the reported pathologic literature is needed as a basis
      for studying the pathogenesis of thrombosis in these syndromes, and therefore we
      present a review of papers that have reported pathology in association with
      phospholipid antibodies. In order to illustrate the review, we present a typical
      case of primary antiphospholipid antibody syndrome. 

PMID- 25850910
TI  - Subvalvular left ventricular outflow tract obstruction caused by "rhinonodular"
      calcification.
AB  - Cardiac calcification is a common problem in patients with renal failure.
      Calcific deposits often affect the mitral annulus, the aortic valve, and the
      coronary arteries. We report an atypical case of cardiac calcification
      obstructing the left ventricular outflow tract with minimal aortic valve
      calcification. 

PMID- 25850911
TI  - A case of giant cell myocarditis with evidence of cardiac autoimmunity.
AB  - A 45-year-old-woman with giant cell myocarditis showing high titer of circulating
      antiheart antibodies is reported. She experienced two recurrences of myocarditis
      and repeatedly responded to immunosuppressive therapy using prednisolone. The
      titer of antiheart antibodies went up and down appropriately according to the
      clinical responses to immunosuppressive therapy. This case suggested that giant
      cell myocarditis might be related to autoimmunity. 

PMID- 25850912
TI  - The effect of prefixation on the quality of vascular corrosion casts of rat
      heart.
AB  - To help define the optimal conditions for the preparation of vascular corrosion
      casts of rat heart, we examined the effect of prefixation with aldehyde fixatives
      on the perfusion rates of rat heart and on the quality of vascular casts. For
      these studies, beating hearts were removed from rats, cannulated via the aortic
      stump, arrested with KCl, perfused retrograde with buffered saline or fixative,
      and infused with resin to prepare corrosion casts. Fixatives used were 2.5%
      glutaraldehyde or 2% paraformaldehyde, and the casting resin consisted of a
      Mercox-methylmethacrylate mixture (4:1). All perfusion pressures were monitored
      at 80 to 100 mm Hg using a mercury manometer. The perfusion rate of control
      hearts was 13 to 14 mL/min. Prefixation with glutaraldehyde and paraformaldehyde
      reduced perfusion to 8.5 and 8.1 mL/min, respectively. Cast quality was observed
      grossly and with the scanning electron microscope. Control hearts yielded high
      quality, complete casts with 2570 capillaries/mm(2+). Casts from prefixed hearts
      exhibited areas of incomplete vessel filling and resisted complete tissue
      maceration, leaving tissue remnants adhering to the vessel replicas. Casts from
      glutaraldehyde-fixed hearts were of very poor quality. Our results indicate that
      prefixation is an unnecessary step in the preparation of vascular casts of rat
      heart and is inconsistent with cast quality. 

PMID- 25850913
TI  - CD30 positive (Ki-1) large cell lymphoma presenting with pericardial
      constriction.
AB  - It is very uncommon for the initial presentation of malignant lymphoma to be one
      of cardiac involvement and for such involvement to precipitate cardiac
      dysfunction attributable to constriction. We describe a CD30 positive (Ki-1)
      anaplastic large cell lymphoma, T-cell type, in a 29-year-old man whose
      presentation was a short history of profound hemodynamic impairment and whose
      clinical course was rapidly fatal. This patient's constrictive physiology was
      attributable to diffuse infiltration of the pericardium and epicardium by the Ki
      1 lymphoma. Our description of this patient is noteworthy, given that the
      clinical and pathologic features of Ki-1 lymphomas are still being characterized.

PMID- 25850914
TI  - Primary undifferentiated sarcoma of the pericardium.
AB  - A 60-year-old woman was found to have a pericardial mass on two-dimensional
      echocardiography and computerized tomography. At autopsy, there was a large tumor
      arising from the epicardial surface of the left ventricle. The tumor encircled
      the great arteries and invaded the wall of the pulmonary artery. Microscopic
      examination showed features of an undifferentiated sarcoma. 

PMID- 25850915
TI  - Coronary artery dissection.

PMID- 25850916
TI  - The Arnold Berliner Award 2015.

PMID- 25850918
TI  - Plateletcrit May Not be a Marker for Recurrent Pregnancy Loss.

PMID- 25850917
TI  - Recurrence of Venous Thromboembolism in Patients With Cancer Treated With
      Warfarin.
AB  - Venous thromboembolism (VTE) is a common complication in patients with cancer.
      Previous randomized studies have demonstrated that the rates of recurrent VTE are
      lower in patients treated with low-molecular-weight heparin compared to warfarin.
      We performed a retrospective analysis of 236 patients with cancer managed by a
      dedicated oncology anticoagulation management service to compare "real-world"
      rates of recurrent VTE and bleeding in patients treated with warfarin versus
      parenteral anticoagulants. Initial anticoagulant regimen included a parenteral
      agent with transition to warfarin in 132 (55.9%) patients, enoxaparin in 53
      (22.5%), dalteparin in 37 (15.7%), and fondaparinux in 14 (5.9%). Taking into
      account the competing risk of death, cumulative incidence of VTE recurrence at 6
      months was 4.0% with warfarin, 10.3% with enoxaparin, 3.0% with dalteparin, and
      7.7% with fondaparinux (P = .004). Bleeding complications occurred in 10.6% of
      patients on warfarin, 17.0% on enoxaparin, 27.0% on dalteparin, and 14.3% on
      fondaparinux (P = .089). In a dedicated anticoagulation clinic, specific for
      patients with cancer, warfarin may be an acceptable treatment for first
      thrombotic events in patients with cancer.

PMID- 25850919
TI  - Early Modification in Drainage of Interleukin-1beta and Tumor Necrosis Factor
      alpha Best Predicts Surgical-Site Infection After Cervical Neck Dissection for
      Oral Cancer.
AB  - PURPOSE: Surgical-site infection (SSI) after cervical neck dissection (CND) for
      head and neck squamous cell carcinoma (HNSCC) increases morbidity and delays
      adjuvant treatment. This study assessed changes in cytokines levels in
      postsurgical drainage fluid after CND and examined their predictive value for the
      early diagnosis of SSI. PATIENTS AND METHODS: An observational prospective pilot
      study was conducted in 39 consecutively recruited patients with HNSCC undergoing
      CND who were treated at the authors' service within the past 2 years. Patients
      met the following inclusion criteria: no previous chemotherapy or radiotherapy,
      closed-suction drainage, 30-day follow-up, prophylactic treatment with
      amoxicillin plus clavulanic acid and dexamethasone, no chronic inflammatory
      disease, and no previous neck surgery. Drainage samples were collected at
      postoperative days +1 and +3. Sample size was estimated based on SSI incidence
      after HNSCC surgery (~15%; alpha risk, 0.05; beta risk, 0.2; 2-sided test).
      Interleukin (IL)-1beta, IL-2, IL-6, IL-8, IL-10, and tumor necrosis factor-alpha
      (TNF-alpha) levels were measured. Patients were followed to detect SSI.
      Sensitivity, specificity, and prognostic values were calculated for each cytokine
      at days +1 and +3 to diagnose SSI. RESULTS: SSI was diagnosed in 6 of 39
      patients. Bilateral CND, tracheostomy, surgery duration longer than 7 hours,
      HNSCC stage T3 or T4, and reconstruction with pedicled flaps versus microvascular
      flaps for advanced-stage tumors were considered risk factors for SSI. All
      cytokines except IL-10 showed statistical differences between patients with SSI
      and those without SSI. The best receiver operating characteristic curves yielded
      cutoff values at day +1 (TNF-alpha >14.5 pg/mL; sensitivity, 100%; specificity,
      87.88%) and day +3 (IL-1beta >115 pg/mL; sensitivity, 83.33%; specificity,
      78.79%). Also, IL-2 levels higher than 6.5 pg/mL at day +1 (sensitivity, 83.33%;
      specificity, 69.7%) and day +3 (sensitivity, 100%; specificity, 69.7%) and IL-6
      levels higher than 3,300 pg/mL at day +3 (sensitivity, 100%; specificity, 60.61%)
      yielded adequate diagnostic profitability. CONCLUSION: The results of this study
      suggest that the assessment of cytokine levels in drainage fluid soon after CND
      could provide a novel method for the early detection of SSI.

PMID- 25850920
TI  - Treatment of Parotid Malignancies-10 Years of Experience.
AB  - PURPOSE: Operative treatment is the main treatment option for parotid gland
      tumors. The purpose of this study was to present the authors' experience in the
      operative treatment of parotid gland malignant tumors, especially regarding
      feasibility and techniques in the most advanced cases. MATERIALS AND METHODS:
      This is a retrospective cohort study of parotid malignancies. The study included
      patients treated at the authors' university clinic from 2000 through 2010. The
      primary predictor variable was stage of disease. The primary outcome variables
      were 3- and 5-year overall and disease-free survival rates. The secondary
      predictor variables were nodal status, distant metastases, status of the facial
      nerve (FN), tumor diameter, extraparotid tumor extension, histology, and surgical
      procedure. The outcome variable was survival rate. Data were analyzed by chi(2)
      tests. RESULTS: Of 867 parotid tumors, 103 patients with malignancies (47 female,
      56 male; 12 to 88 yr old) underwent 24 partial lateral, 34 lateral, 39 total, and
      6 extended parotidectomies. The 3- and 5-year overall survival and 3- and 5-year
      disease-free survival rates for stages T1 and T2 were 100, 99, 91, and 85%,
      respectively, and those for stages T3 and T4 were 100, 70, 48, and 34%,
      respectively. Overall and disease-free survival rates were influenced by FN
      paralysis and histologic type. CONCLUSIONS: Final oncologic outcomes, recurrence,
      and survival rates in parotid malignancies are considerably affected by local
      tumor stage, malignancy, and FN paralysis before treatment. Infiltration of
      adjacent structures is not connected with a poorer prognosis as long as an
      extended parotidectomy is performed.

PMID- 25850921
TI  - Responses of skeletal muscles to gravitational unloading and/or reloading.
AB  - Adaptation of morphological, metabolic, and contractile properties of skeletal
      muscles to inhibition of antigravity activities by exposure to a microgravity
      environment or by simulation models, such as chronic bedrest in humans or
      hindlimb suspension in rodents, has been well reported. Such physiological
      adaptations are generally detrimental in daily life on earth. Since the
      development of suitable countermeasure(s) is essential to prevent or inhibit
      these adaptations, effects of neural, mechanical, and metabolic factors on these
      properties in both humans and animals were reviewed. Special attention was paid
      to the roles of the motoneurons (both efferent and afferent neurograms) and
      electromyogram activities as the neural factors, force development, and/or length
      of sarcomeres as the mechanical factors and mitochondrial bioenergetics as the
      metabolic factors. 

PMID- 25850922
TI  - A protein tyrosine kinase receptor, c-RET signaling pathway contributes to the
      enteric neurogenesis induced by a 5-HT4 receptor agonist at an anastomosis after
      transection of the gut in rodents.
AB  - We previously reported that a serotonin 4 (5-HT4) receptor agonist, mosapride
      citrate (MOS), increased the number of c-RET-positive cells and levels of c-RET
      mRNA in gel sponge implanted in the necks of rats. The 5-HT4 receptor is a G
      protein coupled receptor (GPCR) coupled to G protein Gs-cAMP cascades. We
      investigated the possibility that 5-HT4 receptor activation induced c-RET
      activation and/or PKA activation by elevating cAMP levels. Rodents were orally
      administered MOS by adding it to drinking water for 2 weeks after enteric nerve
      circuit insult via gut transection and anastomosis, together with the RET
      inhibitors withaferin A (WA) and RPI-1 or the PKA inhibitor H89. We then examined
      PGP9.5-positive cells in the newly formed granulation tissue at the anastomotic
      site. MOS significantly increased the number of new neurons, but not when co
      administered with WA or RPI-1. Co-administration of H89 failed to alter MOS
      induced increases in neurogenesis. In conclusion, the c-RET signaling pathway
      contributes to enteric neurogenesis facilitated by MOS, though the contribution
      of PKA activation seems unlikely.

PMID- 25850923
TI  - The cutaneous vasoconstrictor response in lower extremities during whole-body and
      local skin cooling in young women with a cold constitution.
AB  - To clarify the characteristics of the thermal control of skin blood flow (SkBF)
      in individuals with a cold constitution, we examined the cutaneous
      vasoconstrictor responses in the calf and dorsal foot during whole-body and local
      skin cooling in young women complaining of chilliness (C group) and young women
      not suffering from it (N group). During whole-body skin cooling, the
      vasoconstrictor sensitivity in the dorsal foot, but not in the calf, was greater
      in the C group than in the N group. The C group also showed greater
      vasoconstrictor responses in the dorsal foot, but not in the calf, during local
      skin cooling and the iontophoretic application of norepinephrine. These findings
      suggest that the C group possesses a specific SkBF controlling system that is
      characterized by higher adrenergic sensitivity for greater cutaneous
      vasoconstriction in the distal portion of the lower extremities during cold
      exposure. 

PMID- 25850924
TI  - Intraoperative determination of the adequacy of myotomy length during peroral
      endoscopic myotomy (POEM): the double-endoscope transillumination for extent
      confirmation technique (DETECT).
AB  - BACKGROUND AND STUDY AIMS: Precise identification of the gastroesophageal
      junction (GEJ) is a challenging prerequisite for adequate length of an esophageal
      myotomy. Multiple standard methods to identify the GEJ have been described;
      however, a more objective modality is needed to ensure effective peroral
      endoscopic myotomy (POEM). PATIENTS AND METHODS: In the double-endoscope
      transillumination for extent confirmation technique (DETECT), an ultraslim
      gastroscope is passed to the most distal aspect of the submucosal tunnel created
      during POEM. A regular gastroscope is advanced into the stomach, and the
      visualization of transillumination from the ultraslim gastroscope enables
      identification of the extent of the submucosal tunnel. RESULTS: A total of 10
      patients underwent POEM with DETECT. Initial submucosal tunneling was performed
      based on a determination of the GEJ location via standard methods. DETECT
      indicated the tunnel extent to be inadequate in 50% of patients, and the tunnel
      was extended a further 1 to 2cm. The mean initial tunnel length was 15.4cm, with
      a mean initial myotomy length of 11.9cm. DETECT was performed in less than 10
      minutes without complications. CONCLUSION: DETECT is an objective method for
      determining the adequacy of the submucosal tunnel length during POEM.

PMID- 25850926
TI  - A causal role of the right inferior frontal cortex in implementing strategies for
      multi-component behaviour.
AB  - Everyday activities, such as, for example, driving a car or preparing a meal,
      require the hierarchical organization and processing of several individual
      actions. Currently, the neural mechanisms underlying the control of action
      sequences are not well understood. Here, the authors demonstrate that the right
      inferior frontal gyrus (rIFG) plays a key role in implementing the strategy used
      to cascade different actions. Continuous theta burst stimulation (TBS) applied to
      the rIFG results in a less efficient action cascading strategy, whereas
      intermittent TBS results in a more efficient strategy, compared with a shamTBS
      control condition. These effects are confirmed in electrophysiological data
      showing that activity differences in the rIFG are related to alterations in
      response selection processes. Overall, these results suggest that the neural
      dynamics of the rIFG determine the strategy used during some forms of everyday
      multi-component behaviour. 

PMID- 25850927
TI  - A Taenia crassiceps factor induces apoptosis of spleen CD4+T cells and TFG-beta
      and Foxp3 gene expression in mice.
AB  - This study was undertaken to determine whether a parasite substance produces
      structural pathology in the mouse spleen. A low-molecular-weight Taenia
      crassiceps metacestode factor (MF) isolated from the peritoneal fluid of female
      mice infected with T. crassiceps metacestodes induced pathological and
      immunological changes in mouse spleen cells in vivo. Electron microscopy and
      confocal microscopy revealed severe changes in the spleen histoarchitecture of T.
      crassiceps-infected and MF-treated mice. Apoptotic degenerated spleen cells were
      observed in the white and red pulps and were more conspicuous in the white pulp
      of the spleen from the T. crassiceps-infected mice than in that of the MF-treated
      mice. Flow cytometry analysis revealed that the numbers of spleen CD4+T cells
      were significantly lower in both experimental groups than in control mice. The ex
      vivo expression of transforming growth factor (TGF)-beta and factor Foxp3 were
      significantly higher in splenocytes of the experimental mice than the basal
      expression observed in the control cells. These findings may have potential
      applications for a better understanding of the host-parasite relationship in
      human neurocysticercosis. 

PMID- 25850929
TI  - Current radiation therapy techniques for lung cancer and its importance for
      suitable radiological assessment of treatment response in lung cancer.

PMID- 25850928
TI  - The inconspicuous penis in children.
AB  - The term 'inconspicuous penis' refers to a group of anatomical abnormalities in
      which the penis looks smaller than is expected. Micropenis can be defined as
      'true micropenis'--which results from a defect in the hypothalamic-pituitary
      gonadal axis--and 'micropenis secondary to congenital anatomical anomalies of the
      surrounding and overlying structures'--also known as 'concealed penis'. The
      different forms of concealed penis include webbed penis, congenital megaprepuce
      and partially hidden penis caused by prepubic adiposity. This disorder can also
      have iatrogenic causes resulting from adhesions that are secondary to
      circumcision--this type of concealed penis is known as 'trapped penis'. However,
      in both groups, micropenis is defined as a stretched penile length that is at
      least 2.5 SD below the mean for the patient's age, but without any other penile
      defects. Patients with true micropenis can be managed with testosterone, which
      has demonstrated good penile elongation results in the long term. Surgery also
      has a pivotal role in reconstruction for elongating the penis and for correction
      of anatomical abnormalities in concealed penis.

PMID- 25850930
TI  - Distinct methylation patterns in genes that affect mitochondrial function are
      associated with kidney disease in blood-derived DNA from individuals with Type 1
      diabetes.
AB  - AIMS: Epigenetic modifications, such as DNA methylation, can influence the risk
      of developing kidney disease. We studied methylation profiles in genes related to
      mitochondrial function to assess whether differences in these epigenetic features
      were associated with diabetic kidney disease in people with Type 1 diabetes.
      METHODS: A case-control association study was undertaken (n = 196 individuals
      with diabetic kidney disease vs. n = 246 individuals without renal disease).
      Participants were White and diagnosed with Type 1 diabetes before 31 years of
      age. Genes that encode mitochondrial proteins (n = 780) were downloaded from
      mitoproteome.org. DNA methylation profiles from blood-derived DNA were generated
      using the Illumina Infinium HumanMethylation450 (262 samples) and Illumina
      Infinium HumanMethylation27 (192 samples) arrays. Beta values (beta) were
      calculated and quality control was conducted, including evaluating blind
      duplicate DNA samples. RESULTS: Fifty-four Cytosine-phosphate-Guanine probes
      across 51 unique genes were significantly associated (P <= 10(-8) ) with diabetic
      kidney disease across both the 450K and the 27K methylation arrays. A
      subanalysis, employing the 450K array, identified 755 Cytosine-phosphate-Guanine
      probes in 374 genes that were significantly associated (P <= 10(-8) ) with end
      stage renal disease. Forty-six of the top-ranked variants for diabetic kidney
      disease were also identified as being differentially methylated in individuals
      with end-stage renal disease. The largest change in methylation (Deltabeta = 0.2)
      was observed for cg03169527 in the TAMM41 gene, chromosome 3p25.2. Three genes,
      PMPCB, TSFM and AUH, were observed with differential methylation at multiple
      Cytosine-phosphate-Guanine sites each (P < 10(-12) ). CONCLUSIONS: Differential
      methylation in genes that influence mitochondrial function are associated with
      kidney disease in individuals with Type 1 diabetes.

PMID- 25850932
TI  - Self-assembled peptide nanoarchitectures: applications and future aspects.
AB  - Among the diversity of natural and synthetic compounds being studied and applied
      for human welfare, peptides able to develop nanostructures are currently under
      special attention of scientists. In this review, we focus on such properties of
      peptides and various kinds of intramolecular interactions allowing their ability
      to form different shapes of nanoassemblies. We have also discussed the
      applications of self-assembled peptides in various biomedical fields where they
      can be employed as cargo to target delivery of drugs, genes, in tissue
      engineering, regenerative medicines, and biosensors. 

PMID- 25850931
TI  - Breast cancer subtype intertumor heterogeneity: MRI-based features predict
      results of a genomic assay.
AB  - PURPOSE: To investigate the association between a validated, gene-expression
      based, aggressiveness assay, Oncotype Dx RS, and morphological and texture-based
      image features extracted from magnetic resonance imaging (MRI). MATERIALS AND
      METHODS: This retrospective study received Internal Review Board approval and
      need for informed consent was waived. Between 2006-2012, we identified breast
      cancer patients with: 1) ER+, PR+, and HER2- invasive ductal carcinoma (IDC); 2)
      preoperative breast MRI; and 3) Oncotype Dx RS test results. Extracted features
      included morphological, histogram, and gray-scale correlation matrix (GLCM)-based
      texture features computed from tumors contoured on pre- and three postcontrast MR
      images. Linear regression analysis was performed to investigate the association
      between Oncotype Dx RS and different clinical, pathologic, and imaging features.
      P < 0.05 was considered statistically significant. RESULTS: Ninety-five patients
      with IDC were included with a median Oncotype Dx RS of 16 (range: 0-45). Using
      stepwise multiple linear regression modeling, two MR-derived image features,
      kurtosis in the first and third postcontrast images and histologic nuclear grade,
      were found to be significantly correlated with the Oncotype Dx RS with P =
      0.0056, 0.0005, and 0.0105, respectively. The overall model resulted in
      statistically significant correlation with Oncotype Dx RS with an R-squared value
      of 0.23 (adjusted R-squared = 0.20; P = 0.0002) and a Spearman's rank correlation
      coefficient of 0.49 (P < 0.0001). CONCLUSION: A model for IDC using imaging and
      pathology information correlates with Oncotype Dx RS scores, suggesting that
      image-based features could also predict the likelihood of recurrence and
      magnitude of chemotherapy benefit.

PMID- 25850933
TI  - Liquid-liquid phase separation in aerosol particles: imaging at the nanometer
      scale.
AB  - Atmospheric aerosols can undergo phase transitions including liquid-liquid phase
      separation (LLPS) while responding to changes in the ambient relative humidity
      (RH). Here, we report results of chemical imaging experiments using environmental
      scanning electron microscopy (ESEM) and scanning transmission X-ray microscopy
      (STXM) to investigate the LLPS of micrometer-sized particles undergoing a full
      hydration-dehydration cycle. Internally mixed particles composed of ammonium
      sulfate (AS) and either: limonene secondary organic carbon (LSOC), alpha, 4
      dihydroxy-3-methoxybenzeneaceticacid (HMMA), or polyethylene glycol (PEG-400)
      were studied. Events of LLPS were observed for all samples with both techniques.
      Chemical imaging with STXM showed that both LSOC/AS and HMMA/AS particles were
      never homogeneously mixed for all measured RH's above the deliquescence point and
      that the majority of the organic component was located in the outer phase. The
      outer phase composition was estimated as 65:35 organic: inorganic in LSOC/AS and
      as 50:50 organic: inorganic for HMMA/AS. PEG-400/AS particles showed fully
      homogeneous mixtures at high RH and phase separated below 89-92% RH with an
      estimated 70:30% organic to inorganic mix in the outer phase. These two chemical
      imaging techniques are well suited for in situ analysis of the hygroscopic
      behavior, phase separation, and surface composition of collected ambient aerosol
      particles. 

PMID- 25850934
TI  - Attenuated SAG expression exacerbates 4-hydroxy-2-nonenal-induced apoptosis and
      hypertrophy of H9c2 cardiomyocytes.
AB  - Oxidative stress, associated with the accumulation of reactive oxygen species
      (ROS), results in numerous and detrimental effects on the myocardium such as the
      induction of apoptotic cell death, hypertrophy, fibrosis, dysfunction, and
      dilatation. The product of sensitive to apoptosis gene (SAG) is a RING finger
      protein that has been shown to have a protective effect against apoptosis induced
      by oxidative stress in various cell types. The major reactive aldehydic product
      of lipid peroxidation, 4-hydroxy-2-nonenal (HNE), is believed to be largely
      responsible for cytopathological effects observed during oxidative stress. In the
      present study, we showed that the transfection of H9c2 clonal myoblastic cells
      with small interfering RNA (siRNA) specific for SAG markedly attenuated SAG
      expression and exacerbates HNE-induced apoptosis and hypertrophy. The knockdown
      of SAG expression resulted in the modulation of cellular redox status,
      mitochondrial function, and cellular oxidative damage. Taken together, our
      results showed that the suppression of SAG expression by siRNA enhanced HNE
      induced apoptosis and hypertrophy of cultured cardiomyocytes via the disruption
      of the cellular redox balance. Given the importance of the SAG protein in the
      regulation of the redox status of cardiomyocytes, we conclude that this protein
      may be a potential new target in the development of therapeutic agents for the
      prevention of cardiovascular diseases. 

PMID- 25850935
TI  - Onset of photosynthesis in spring speeds up monoterpene synthesis and leads to
      emission bursts.
AB  - Emissions of biogenic volatile organic compounds (BVOC) by boreal evergreen trees
      have strong seasonality, with low emission rates during photosynthetically
      inactive winter and increasing rates towards summer. Yet, the regulation of this
      seasonality remains unclear. We measured in situ monoterpene emissions from Scots
      pine shoots during several spring periods and analysed their dynamics in
      connection with the spring recovery of photosynthesis. We found high emission
      peaks caused by enhanced monoterpene synthesis consistently during every spring
      period (monoterpene emission bursts, MEB). The timing of the MEBs varied
      relatively little between the spring periods. The timing of the MEBs showed good
      agreement with the photosynthetic spring recovery, which was studied with
      simultaneous measurements of chlorophyll fluorescence, CO2 exchange and a simple,
      temperature history-based proxy for state of photosynthetic acclimation, S. We
      conclude that the MEBs were related to the early stages of photosynthetic
      recovery, when the efficiency of photosynthetic carbon reactions is still low
      whereas the light harvesting machinery actively absorbs light energy. This
      suggests that the MEBs may serve a protective functional role for the foliage
      during this critical transitory state and that these high emission peaks may
      contribute to atmospheric chemistry in the boreal forest in springtime.

PMID- 25850937
TI  - Localization of the Trace Elements Iron, Zinc and Selenium in Relation to
      Anatomical Structures in Bovine Ovaries by X-Ray Fluorescence Imaging.
AB  - X-ray fluorescence (XRF) was used to image 40 histological cross-sections of
      bovine ovaries (n=19), focusing on structures including: antral follicles at
      different stages of growth or atresia, corpora lutea at three stages of
      development (II-IV), and capillaries, arterioles, and other blood vessels. This
      method identified three key trace elements [iron (Fe), zinc (Zn), and selenium
      (Se)] within the ovarian tissue which appeared to be localized to specific
      structures. Owing to minimal preprocessing of the ovaries, important high
      resolution information regarding the spatial distribution of these elements was
      obtained with elemental trends and colocalizations of Fe and Zn apparent, as well
      as the infrequent appearance of Se surrounding the antrum of large follicles, as
      previously reported. The ability to use synchrotron radiation to measure trace
      element distributions in bovine ovaries at such high resolution and over such
      large areas could have a significant impact on understanding the mechanisms of
      ovarian development. This research is intended to form a baseline study of
      healthy ovaries which can later be extended to disease states, thereby improving
      our current understanding of infertility and endocrine diseases involving the
      ovary. 

PMID- 25850939
TI  - Ratio of neutrophilic CD64 and monocytic HLA-DR: A novel parameter in diagnosis
      and prognostication of neonatal sepsis.
AB  - OBJECTIVE: Approaches to monitoring of sepsis have traditionally relied upon the
      pro-inflammatory component of the sepsis response. This study evaluated the
      diagnostic and prognostic potential of the ratio of neutrophilic CD64 (nCD64) and
      monocytic HLA-DR (mHLA-DR) median fluorescence index in monitoring of neonatal
      sepsis. METHODS: Blood from 100 neonates suspected of sepsis and 29 healthy
      controls was collected on clinical suspicion of sepsis, and the expression of
      nCD64, mHLA-DR was evaluated by Flow Cytometry; thereby, a derived parameter
      "Sepsis index," SI = nCD64/mHLA-DR * 100 was estimated. RESULTS: At day 1,
      sensitivity and specificity to detect sepsis using nCD64 was 73.01% and 89.18%,
      respectively, while for SI it was 73.01% and 72.22%, respectively. On Kaplan
      Meier analysis, neonates with SI > cut-off showed a higher 30 day-mortality than
      those with low SI (P = 0.096). On multivariate analysis, the factor associated
      with mortality in our cohort was Apgar score <=3, while SI showed a trend toward
      significance. CONCLUSIONS: At day1, nCD64 is useful for the diagnosis of neonatal
      sepsis whereas mHLA-DR is beneficial for monitoring patients at a later time
      point. The SI is a marker of moderate diagnostic sensitivity and supplements the
      current arsenal of laboratory investigations to detect neonatal sepsis. As a
      marker of prognosis, a high SI shows a trend towards greater mortality. (c) 2015
      Clinical Cytometry Society.

PMID- 25850940
TI  - Adiabaticity of the proton-coupled electron-transfer step in the reduction of
      superoxide effected by nickel-containing superoxide dismutase metallopeptide
      based mimics.
AB  - Nickel-containing superoxide dismutases (NiSODs) are bacterial metalloenzymes
      that catalyze the disproportionation of O2(-). These enzymes take advantage of a
      redox-active nickel cofactor, which cycles between the Ni(II) and Ni(III)
      oxidation states, to catalytically disprotorptionate O2(-). The Ni(II) center is
      ligated in a square planar N2S2 coordination environment, which, upon oxidation
      to Ni(III), becomes five-coordinate following the ligation of an axial imidazole
      ligand. Previous studies have suggested that metallopeptide-based mimics of NiSOD
      reduce O2(-) through a proton-coupled electron transfer (PCET) reaction with the
      electron derived from a reduced Ni(II) center and the proton from a protonated,
      coordinated Ni(II)-S(H(+))-Cys moiety. The current work focuses on the O2(-)
      reduction half-reaction of the catalytic cycle. In this study we calculate the
      vibronic coupling between the reactant and product diabatic surfaces using a
      semiclassical formalism to determine if the PCET reaction is proceeding through
      an adiabatic or nonadiabatic proton tunneling process. These results were then
      used to calculate H/D kinetic isotope effects for the PCET process. We find that
      as the axial imidazole ligand becomes more strongly associated with the Ni(II)
      center during the PCET reaction, the reaction becomes more nonadiabatic. This is
      reflected in the calculated H/D KIEs, which moderately increase as the reaction
      becomes more nonadiabatic. Furthermore, the results suggest that as the axial
      ligand becomes less Lewis basic the observed reaction rate constants for O2(-)
      reduction should become faster because the reaction becomes more adiabatic. These
      conclusions are in-line with experimental observations. The results thus indicate
      that variations in the axial donor's ability to coordinate to the nickel center
      of NiSOD metallopeptide-based mimics will strongly influence the fundamental
      nature of the O2(-) reduction process. 

PMID- 25850941
TI  - The development and validation of new equations for estimating body fat
      percentage among Chinese men and women.
AB  - Equations based on simple anthropometric measurements to predict body fat
      percentage (BF%) are lacking in Chinese population with increasing prevalence of
      obesity and related abnormalities. We aimed to develop and validate BF% equations
      in two independent population-based samples of Chinese men and women. The
      equations were developed among 960 Chinese Hans living in Shanghai (age 46.2 (SD
      5.3) years; 36.7% male) using a stepwise linear regression and were subsequently
      validated in 1150 Shanghai residents (58.7 (SD 6.0) years; 41.7% male; 99%
      Chinese Hans, 1% Chinese minorities). The associations of equation-derived BF%
      with changes of 6-year cardiometabolic outcomes and incident type 2 diabetes
      (T2D) were evaluated in a sub-cohort of 780 Chinese, compared with BF% measured
      by dual-energy X-ray absorptiometry (DXA; BF%-DXA). Sex-specific equations were
      established with age, BMI and waist circumference as independent variables. The
      BF% calculated using new sex-specific equations (BF%-CSS) were in reasonable
      agreement with BF%-DXA (mean difference: 0.08 (2 SD 6.64) %, P= 0.606 in men;
      0.45 (2 SD 6.88) %, P< 0.001 in women). In multivariate-adjusted models, the BF%
      CSS and BF%-DXA showed comparable associations with 6-year changes in TAG, HDL
      cholesterol, diastolic blood pressure, C-reactive protein and uric acid (P for
      comparisons >= 0.05). Meanwhile, the BF%-CSS and BF%-DXA had comparable areas
      under the receiver operating characteristic curves for associations with incident
      T2D (men P= 0.327; women P= 0.159). The BF% equations might be used as surrogates
      for DXA to estimate BF% among adult Chinese. More studies are needed to evaluate
      the application of our equations in different populations.

PMID- 25850942
TI  - Molecular signature of erythroblast enucleation in human embryonic stem cells.
AB  - While enucleation is a critical step in the terminal differentiation of human red
      blood cells, the molecular mechanisms underlying this unique process remain
      unclear. To investigate erythroblast enucleation, we studied the erythroid
      differentiation of human embryonic stem cells (hESCs), which provide a unique
      model for deeper understanding of the development and differentiation of multiple
      cell types. First, using a two-step protocol, we demonstrated that terminal
      erythroid differentiation from hESCs is directly dependent on the age of the
      embryoid bodies. Second, by choosing hESCs in two extreme conditions of erythroid
      culture, we obtained an original differentiation model which allows one to study
      the mechanisms underlying the enucleation of erythroid cells by analyzing the
      gene and miRNA (miR) expression profiles of cells from these two culture
      conditions. Third, using an integrated analysis of mRNA and miR expression
      profiles, we identified five miRs potentially involved in erythroblast
      enucleation. Finally, by selective knockdown of these five miRs we found miR-30a
      to be a regulator of erythroblast enucleation in hESCs.

PMID- 25850944
TI  - 2015 SCAI/ACC/HFSA/STS Clinical Expert Consensus Statement on the Use of
      Percutaneous Mechanical Circulatory Support Devices in Cardiovascular Care
      (Endorsed by the American Heart Association, the Cardiological Society of India,
      and Sociedad Latino Americana de Cardiologia Intervencionista; Affirmation of
      Value by the Canadian Association of Interventional Cardiology-Association
      Canadienne de Cardiologie d'intervention).
AB  - This article provides a brief summary of the relevant recommendations and
      references related to percutaneous mechanical circulatory support. The goal was
      to provide the clinician with concise, evidence-based contemporary
      recommendations, and the supporting documentation to encourage their application.
      The full text includes disclosure of all relevant relationships with industry for
      each writing committee member. A fundamental aspect of all expert consensus
      statements is that these carefully developed, evidence-based documents can
      neither encompass all clinical circumstances, nor replace the judgment of
      individual physicians in management of each patient. The science of medicine is
      rooted in evidence, and the art of medicine is based on the application of this
      evidence to the individual patient. This expert consensus statement has adhered
      to these principles for optimal management of patients requiring percutaneous
      mechanical circulatory support.

PMID- 25850945
TI  - Mitochondrial DNA Polymerase gamma Mutations and Their Implications in mtDNA
      Alterations in Colorectal Cancer.
AB  - Mitochondrial DNA was found to be highly mutated in colorectal cancer cells. One
      of the key molecules involved in the maintenance of the mitochondrial genome is
      the nuclear-encoded polymerase gamma. The aim of our study was to determine if
      there is a link between polymorphisms within the polymerase gamma gene (POLG) and
      somatic mutations within the mitochondrial genome in cancer cells. We
      investigated POLG sequence variability in 50 colorectal cancer patients whose
      complete mitochondrial genome sequences were determined. Relative mtDNA copy
      number was also determined. We identified 251 sequence variants in the POLG gene.
      Most of them were germline-specific (~92%). Twenty-one somatic changes in POLG
      were found in 10 colorectal cancer patients. We have found no association between
      the occurrence of mtDNA somatic mutations and the somatically occurring variants
      in POLG. MtDNA content was reduced in patients carrying somatic variants in POLG
      or germline nucleotide variants located in the region encoding the POLG
      polymerase domain, but the difference did not reach statistical significance. Our
      findings suggest that somatic mtDNA mutations occurring in colorectal cancer are
      not a consequence of somatic mutations in POLG. Nevertheless, POLG nucleotide
      variants may lead to a decrease in mtDNA content, and consequently result in
      mitochondrial dysfunction.

PMID- 25850943
TI  - Uncovering the genomic heterogeneity of multifocal breast cancer.
AB  - Multifocal breast cancer (MFBC), defined as multiple synchronous unilateral
      lesions of invasive breast cancer, is relatively frequent and has been associated
      with more aggressive features than unifocal cancer. Here, we aimed to investigate
      the genomic heterogeneity between MFBC lesions sharing similar histopathological
      parameters. Characterization of different lesions from 36 patients with ductal
      MFBC involved the identification of non-silent coding mutations in 360 protein
      coding genes (171 tumour and 36 matched normal samples). We selected only
      patients with lesions presenting the same grade, ER, and HER2 status. Mutations
      were classified as 'oncogenic' in the case of recurrent substitutions reported in
      COSMIC or truncating mutations affecting tumour suppressor genes. All mutations
      identified in a given patient were further interrogated in all samples from that
      patient through deep resequencing using an orthogonal platform. Whole-genome
      rearrangement screen was further conducted in 8/36 patients. Twenty-four patients
      (67%) had substitutions/indels shared by all their lesions, of which 11 carried
      the same mutations in all lesions, and 13 had lesions with both common and
      private mutations. Three-quarters of those 24 patients shared oncogenic variants.
      The remaining 12 patients (33%) did not share any substitution/indels, with inter
      lesion heterogeneity observed for oncogenic mutation(s) in genes such as PIK3CA,
      TP53, GATA3, and PTEN. Genomically heterogeneous lesions tended to be further
      apart in the mammary gland than homogeneous lesions. Genome-wide analyses of a
      limited number of patients identified a common somatic background in all studied
      MFBCs, including those with no mutation in common between the lesions. To
      conclude, as the number of molecular targeted therapies increases and trials
      driven by genomic screening are ongoing, our findings highlight the presence of
      genomic inter-lesion heterogeneity in one-third, despite similar pathological
      features. This implies that deeper molecular characterization of all MFBC lesions
      is warranted for the adequate management of those cancers.

PMID- 25850946
TI  - Temporal characterization of protein production levels from baculovirus vectors
      coding for GFP and RFP genes under non-conventional promoter control.
AB  - The ease of use and versatility of the Baculovirus Expression Vector System
      (BEVS) has made it one of the most widely used systems for recombinant protein
      production However, co-expression systems currently in use mainly make use of the
      very strong very late p10 and polyhedron (polh) promoters to drive expression of
      foreign genes, which does not provide much scope for tailoring expression ratios
      within the cell. This work demonstrates the use of different Autographa
      californica multicapsid nucleopolyhedrovirus (AcMNPV) promoters to control the
      timing and expression of two easily traceable fluorescent proteins, the enhanced
      green fluorescent protein (eGFP), and a red fluorescent protein (DsRed2) in a
      BEVS co-expression system. Our results show that gene expression levels can
      easily be controlled using this strategy, and also that modulating the expression
      level of one protein can influence the level of expression of the other protein
      within the system, thus confirming the concept of genes "competing" for limited
      cellular resources. Plots of "expression ratios" of the two model genes over time
      were obtained, and may be used in future work to tightly control timing and
      levels of foreign gene expression in an insect cell co-expression system.

PMID- 25850947
TI  - Novel detergent for whole organ tissue engineering.
AB  - Whole organ tissue engineering for various organs, including the heart, lung,
      liver, and kidney, has demonstrated promising results for end-stage organ
      failure. However, the sodium dodecyl sulfate (SDS)-based protocol for standard
      decellularization has drawbacks such as clot formation in vascularized
      transplantation and poor cell engraftment in recellularization procedures.
      Preservation of the surface milieu of extracellular matrices (ECMs) might be
      crucial for organ generation based on decellularization/recellularization
      engineering. We examined a novel detergent, sodium lauryl ether sulfate (SLES),
      to determine whether it could overcome the drawbacks associated with SDS using
      rat heart and kidney. Both organs were perfused in an antegrade fashion with
      either SLES or SDS. Although immunohistochemistry for collagen I, IV, laminin,
      and fibronectin showed similar preservation in both detergents, morphological
      analysis using scanning electron microscopy and an assay of glycosaminoglycan
      content on ECMs showed that SLES-treated tissues had better-preserved ECMs than
      SDS-treated tissues. Mesenteric transplantation revealed SLES did not induce
      significant inflammation, as opposed to SDS. Platelet adhesion to decellularized
      tissues was significantly reduced with SLES. Overall, SLES could replace older
      detergents such as SDS in the decellularization process for generation of
      transplantable recellularized organs.

PMID- 25850948
TI  - Lack of effect of sacral nerve stimulation for incontinence in patients with
      systemic sclerosis.
AB  - AIM: Systemic sclerosis (SSc) is a multisystem disorder of unknown aetiology
      leading to the deposition of excessive connective tissue in the skin, blood
      vessels and internal organs. Gastrointestinal involvement occurs in 90% of cases
      and the prevalence of faecal incontinence (FI) is 38%. This study comprises the
      largest case series assessing the efficacy of sacral nerve stimulation (SNS)
      treatment for incontinence in this patient group. METHOD: A retrospective
      analysis on prospectively collected data was performed on all SSc patients from
      our two centres who had undergone SNS for FI. RESULTS: Ten female patients of
      mean age of 54 (37-72) years had temporary SNS performed. The mean duration of FI
      was 13 (2-25) years. All had passive FI. Each patient had preprocedure anorectal
      physiology and endoanal ultrasound examinations documenting internal sphincter
      atrophy/fragmentation or reduced anal resting pressure. Overall there was no
      statistically significant difference (P = 0.57) in the total Wexner incontinence
      scores before (mean 15.1 +/- 2.6 SD) and during temporary SNS procedures (mean
      13.1 +/- 3.6 SD). Two patients with a significant improvement went on to have
      permanent SNS with only one achieving a favourable outcome at 1 year. CONCLUSION:
      This study showed that SNS failed to reduce episodes of leakage in nine out of 10
      patients with systemic sclerosis affected with incontinence.

PMID- 25850949
TI  - Microtensile bond strength of lithium disilicate to zirconia with the CAD-on
      technique.
AB  - PURPOSE: Recently, a novel technique was introduced to combine lithium disilicate
      and zirconia into one restoration. The purpose of this study was to compare the
      microtensile bond strength of veneering ceramic to a zirconia core in two
      techniques: the e.max(r) CAD-on technique and the Press-on technique. MATERIALS
      AND METHODS: Group A was prepared by veneering sintered zirconia blocks (e.max(r)
      ZirCAD) with lithium disilicate blocks (e.max(r) CAD) using the CAD-on technique
      according to manufacturer's instructions. Group B was prepared by taking sintered
      e.max(r) ZirCAD blocks and veneering them with fluorapatite glass-ceramic
      (e.max(r) ZirPress) using the Press-on technique according to manufacturer's
      instructions. Each block was loaded in a dynamic cyclic loading machine. The
      blocks were then sectioned into 1 * 1 mm(2) beams (n = 43) using a precision saw,
      thermocycled, and loaded in tension until failure on a universal testing machine.
      A mean and standard deviation were determined per group. Data were analyzed using
      an unpaired t-test (alpha = 0.05). RESULTS: The mean microtensile bond strengths
      were 44.0 +/- 13.8 MPa for the CAD-on technique and 14.9 +/- 8.8 MPa for the
      Press-on technique. Significant differences were found between the two groups (p
      = 2.7E-19). CONCLUSIONS: The CAD-on technique (lithium disilicate/zirconia)
      resulted in greater microtensile bond strength than the Press-on technique
      (fluorapatite glass-ceramic/zirconia).

PMID- 25850950
TI  - Phase I Hepatic Immunotherapy for Metastases Study of Intra-Arterial Chimeric
      Antigen Receptor-Modified T-cell Therapy for CEA+ Liver Metastases.
AB  - PURPOSE: Chimeric antigen receptor-modified T cells (CAR-T) have demonstrated
      encouraging results in early-phase clinical trials. Successful adaptation of CAR
      T technology for CEA-expressing adenocarcinoma liver metastases, a major cause of
      death in patients with gastrointestinal cancers, has yet to be achieved. We
      sought to test intrahepatic delivery of anti-CEA CAR-T through percutaneous
      hepatic artery infusions (HAIs). EXPERIMENTAL DESIGN: We conducted a phase I
      trial to test HAI of CAR-T in patients with CEA(+) liver metastases. Six patients
      completed the protocol, and 3 received anti-CEA CAR-T HAIs alone in dose
      escalation fashion (10(8), 10(9), and 10(10) cells). We treated an additional 3
      patients with the maximum planned CAR-T HAI dose (10(10) cells * 3) along with
      systemic IL2 support. RESULTS: Four patients had more than 10 liver metastases,
      and patients received a mean of 2.5 lines of conventional systemic therapy before
      enrollment. No patient suffered a grade 3 or 4 adverse event related to the CAR-T
      HAIs. One patient remains alive with stable disease at 23 months following CAR-T
      HAI, and 5 patients died of progressive disease. Among the patients in the cohort
      that received systemic IL2 support, CEA levels decreased 37% (range, 19%-48%)
      from baseline. Biopsies demonstrated an increase in liver metastasis necrosis or
      fibrosis in 4 of 6 patients. Elevated serum IFNgamma levels correlated with IL2
      administration and CEA decreases. CONCLUSIONS: We have demonstrated the safety of
      anti-CEA CAR-T HAIs with encouraging signals of clinical activity in a heavily
      pretreated population with large tumor burdens. Further clinical testing of CAR-T
      HAIs for liver metastases is warranted.

PMID- 25850952
TI  - Accelerated whole-brain multi-parameter mapping using blind compressed sensing.
AB  - PURPOSE: To introduce a blind compressed sensing (BCS) framework to accelerate
      multi-parameter MR mapping, and demonstrate its feasibility in high-resolution,
      whole-brain T1rho and T2 mapping. METHODS: BCS models the evolution of
      magnetization at every pixel as a sparse linear combination of bases in a
      dictionary. Unlike compressed sensing, the dictionary and the sparse coefficients
      are jointly estimated from undersampled data. Large number of non-orthogonal
      bases in BCS accounts for more complex signals than low rank representations. The
      low degree of freedom of BCS, attributed to sparse coefficients, translates to
      fewer artifacts at high acceleration factors (R). RESULTS: From 2D retrospective
      undersampling experiments, the mean square errors in T1rho and T2 maps were
      observed to be within 0.1% up to R = 10. BCS was observed to be more robust to
      patient-specific motion as compared to other compressed sensing schemes and
      resulted in minimal degradation of parameter maps in the presence of motion. Our
      results suggested that BCS can provide an acceleration factor of 8 in prospective
      3D imaging with reasonable reconstructions. CONCLUSION: BCS considerably reduces
      scan time for multiparameter mapping of the whole brain with minimal artifacts,
      and is more robust to motion-induced signal changes compared to current
      compressed sensing and principal component analysis-based techniques.

PMID- 25850954
TI  - Low-temperature liquid phase reduced TiO2 nanotube arrays: synergy of morphology
      manipulation and oxygen vacancy doping for enhancement of field emission.
AB  - The partially reduced TiO(2) nanotube arrays (TNAs) are prepared via an
      uncomplicated and low-cost liquid phase reduction strategy using NaBH(4) as the
      reducing agent. By controlling and adjusting the reduction temperatures from 30
      to 90  degrees C, the reduction treatment can not only change their surface
      morphology but also introduce oxygen vacancies into them, resulting in an
      optimized morphology, elevated Fermi-level, reduced effective work function and
      improved conductivity of the TNAs. Meanwhile, the thermal and long-term stability
      of oxygen vacancy are also investigated, indicating that the oxygen vacancies
      retain long-term stability from room temperature up to 150  degrees C. More
      interesting, partially reduced TNAs show drastically enhanced field emission (FE)
      performances including substantially decreased turn-on field from 18.86 to 1.53 V
      MUm(-1), a high current density of 4.00 mA cm(-2) at 4.52 V MUm(-1), and an
      excellent FE stability and repeatability. These very promising results are
      attributed to the combination of the optimized morphology and introduced oxygen
      vacancies, which can increase FE sites, reduce effective work function and
      increase conductivity.

PMID- 25850953
TI  - Aromatase expression is linked to estrogenic sensitivity of periurethral muscles
      in female rabbits.
AB  - Beyond its role in the conversion of androgens to estrogens, the expression of
      aromatase could influence on the estrogenic signalling in targeted tissues.
      Considering the well-defined biochemical and physiological differences between
      the pubococcygeus (Pcm) and bulbospongiosus (Bsm) muscles in female rabbits, it
      is presently hypothesized that the aromatase expression is differentially linked
      to the estrogen sensitivity of each muscle. To this end, serum estradiol levels
      and the aromatase expression, presence of ERalpha and ERbeta and morphometry were
      evaluated in the Pcm and Bsm of female rabbits allocated in control,
      ovariectomized (OVX) and OVX treated with estradiol benzoate (OVX + EB) groups.
      Aromatase expression was high in the Pcm. Independently to serum estradiol,
      ovariectomy increased aromatase expression in the Pcm while decreased it in the
      Bsm. The EB treatment avoided the effect of ovariectomy only in the Pcm. The
      number of immunoreactive nuclei anti-ERalpha and anti-ERbeta was high in the Pcm
      of OVX and OVX + EB rabbits, while those in the Bsm remained unchanged. The
      number of peripheral nuclei per fibre and the cross-sectional area-to-myonucleus
      ratio were modified only in the Pcm. Our findings support aromatase expression in
      the Pcm, and Bsm of rabbits is differentially linked to estrogenic sensitivity of
      each muscle.

PMID- 25850955
TI  - Rapid and simple preparation of thiol-ene emulsion-templated monoliths and their
      application as enzymatic microreactors.
AB  - A novel, rapid and simple method for the preparation of emulsion-templated
      monoliths in microfluidic channels based on thiol-ene chemistry is presented. The
      method allows monolith synthesis and anchoring inside thiol-ene microchannels in
      a single photoinitiated step. Characterization by scanning electron microscopy
      showed that the methanol-based emulsion templating process resulted in a network
      of highly interconnected and regular thiol-ene beads anchored solidly inside
      thiol-ene microchannels. Surface area measurements indicate that the monoliths
      are macroporous, with no or little micro- or mesopores. As a demonstration,
      galactose oxidase and peptide-N-glycosidase F (PNGase F) were immobilized at the
      surface of the synthesized thiol-ene monoliths via two different mechanisms.
      First, cysteine groups on the protein surface were used for reversible covalent
      linkage to free thiol functional groups on the monoliths. Second, covalent
      linkage was achieved via free primary amino groups on the protein surface by
      means of thiol-ene click chemistry and l-ascorbic acid linkage. Thus prepared
      galactose oxidase and PNGase F microreactors demonstrated good enzymatic activity
      in a galactose assay and the deglycosilation of ribonuclease B, respectively. 

PMID- 25850956
TI  - Oromandibular dystonia: a serious side effect of capecitabine.
AB  - BACKGROUND: Capecitabine has activity against several types of cancer. In 10-15%
      of patients treated with capecitabine, treatment is discontinued because of
      serious adverse reactions, mostly within the first weeks of treatment. CASE
      PRESENTATION: A 56 year-old female patient presented at the emergency department
      after ten days of chemotherapy with progressive airway obstruction and complaints
      of numbness of the tongue. She also had difficulty swallowing and was unable to
      speak. Laboratory findings were completely normal and no co-medication was used,
      in particular no dopamine antagonists. CONCLUSION: The case highlights the need
      for awareness that capecitabine may potentially lead to severe life-threatening
      complaints of oromandibular dystonia. We hypothesize that capecitabine passed the
      blood brain barrier which led to a disruption within the basal ganglia in this
      case. Prompt treatment with an anticholinergic drug and cessation of capecitabine
      in the patient case led to disappearance of complaints.

PMID- 25850957
TI  - The effect of LKB1 on the PI3K/Akt pathway activation in association with PTEN
      and PIK3CA in HNC.
AB  - OBJECTIVE: PI3K/Akt signalling pathway is frequently activated in several types
      of cancer. However, activator molecules have not been analysed systematically in
      HNSCC. The aim of this study was to investigate upstream activators and
      inhibitors of this pathway. DESIGN: Prospective study. SETTING: University
      hospital. PARTICIPANTS: 108 patients with HNC who were operated at the Istanbul
      University, Cerrahpasa Medical Faculty, Department of Otorhinolaryngology.
      METHODS: Mutations in the coding exons and the flanking intronic sequences of the
      PIK3CA, PIK3R1 and AKT1 genes were analysed by direct sequencing. Expression
      levels in the tumours and non-cancerous tissue samples were analysed by
      quantitative RT-PCR, and Western blotting was performed to determine the
      phosphorylation levels of the Akt1 protein. RESULTS: Two synonymous alterations
      in exon 20 of the PIK3CA gene, a 6-bp duplication in the coding region of the
      PIK3R1 and two different alterations in the non-coding regions of the AKT1 and
      PIK3R1 genes were observed. Significant downregulation of LKB1 and PTEN mRNA
      expression levels were detected in tumour tissues compared to non-cancerous
      tissues. However, we did not observe any difference between the PIK3CA and AKT1
      mRNA expression levels in the tumours and non-cancerous tissue samples. Akt1
      phosphorylation was increased in 53.57% of the patients. CONCLUSIONS: Our results
      indicate that the PI3K pathway has an important function in HNSCC progression
      with the contribution of more than one gene of this pathway. Our data suggest
      that in a high number of HNSCC tumours, PI3K/Akt signalling is activated by
      different molecules or by the combination of these molecules.

PMID- 25850958
TI  - Diagnostic algorithms in Charcot-Marie-Tooth neuropathies: experiences from a
      German genetic laboratory on the basis of 1206 index patients.
AB  - We present clinical features and genetic results of 1206 index patients and 124
      affected relatives who were referred for genetic testing of Charcot-Marie-Tooth
      (CMT) neuropathy at the laboratory in Aachen between 2001 and 2012. Genetic
      detection rates were 56% in demyelinating CMT (71% of autosomal dominant (AD)
      CMT1/CMTX), and 17% in axonal CMT (24% of AD CMT2/CMTX). Three genetic defects
      (PMP22 duplication/deletion, GJB1/Cx32 or MPZ/P0 mutation) were responsible for
      89.3% of demyelinating CMT index patients in whom a genetic diagnosis was
      achieved, and the diagnostic yield of the three main genetic defects in axonal
      CMT (GJB1/Cx32, MFN2, MPZ/P0 mutations) was 84.2%. De novo mutations were
      detected in 1.3% of PMP22 duplication, 25% of MPZ/P0, and none in GJB1/Cx32.
      Motor nerve conduction velocity was uniformly <38 m/s in median or ulnar nerves
      in PMP22 duplication, >40 m/s in MFN2, and more variable in GJB1/Cx32, MPZ/P0
      mutations. Patients with CMT2A showed a broad clinical severity regardless of the
      type or position of the MFN2 mutation. Out of 75 patients, 8 patients (11%) with
      PMP22 deletions were categorized as CMT1 or CMT2. Diagnostic algorithms are still
      useful for cost-efficient mutation detection and for the interpretation of large
      scale genetic data made available by next generation sequencing strategies.

PMID- 25850959
TI  - A Conjugate Class of Utility Functions for Sequential Decision Problems.
AB  - The use of the conjugacy property for members of the exponential family of
      distributions is commonplace within Bayesian statistical analysis, allowing for
      tractable and simple solutions to problems of inference. However, despite a
      shared motivation, there has been little previous development of a similar
      property for using utility functions within a Bayesian decision analysis. As
      such, this article explores a class of utility functions that appear to be
      reasonable for modeling the preferences of a decisionmaker in many real-life
      situations, but that also permit a tractable and simple analysis within
      sequential decision problems. 

PMID- 25850960
TI  - Openness and honesty in gaining fully informed consent will benefit both patients
      and doctors.

PMID- 25850961
TI  - Temporal dynamics of neural activity in motor execution and inhibition
      processing.
AB  - Although many neuroimaging studies using functional magnetic resonance imaging
      have shown the neuronal networks for motor execution and inhibition processing,
      the precise activation timing of each brain region is not yet well understood. In
      the present study, we investigated the temporal dynamics of neural activities in
      multiple brain regions using magnetoencephalography (MEG) and
      electroencephalography (EEG) simultaneously during somatosensory Go/No-go
      paradigms. The results of MEG showed that neural activities in the bilateral
      premotor area at approximately 150 ms and in the primary motor cortex at
      approximately 250 ms were only detected in Go trials, while brain responses in
      the bilateral prefrontal cortex at approximately 170 ms were only observed in No
      go trials. In addition, the amplitudes of the N140 and P300 components in EEG was
      significantly larger in No-go trials than in Go trials, and the latencies of N140
      and P300 were significantly later in No-go trials than in Go trials. Our results
      indicated the time courses of neural processing in response execution and
      inhibition processing, and revealed differences in their underlying neural
      mechanisms. 

PMID- 25850962
TI  - Evaluation of stone-free rate using Guy's Stone Score and assessment of
      complications using modified Clavien grading system for percutaneous nephro
      lithotomy.
AB  - To prospectively evaluate the ability of Guy's Stone Score (GSS) in predicting
      stone clearance rate and complication rate (by modified Clavien grade) for renal
      stones treated by percutaneous nephrolithotomy (PNL). From January 2013 to June
      2014, a total of 142 patients undergoing PNL were evaluated prospectively.
      Patients with co-morbidities like hypertension, diabetes, renal failure were
      excluded from the study. All patients were classified according to GSS based on
      the findings of pre-operative intravenous urography (IVU) and per-operative
      retrograde pyelography (RGP). All PNL procedures were done by standard technique
      in prone position and success was defined as no residual stone visible on X-ray
      KUB done on the third postoperative day. Complications were classified according
      to modified Clavien grading system. The initial stone clearance rate was 71.1%
      and overall final stone clearance rate was 90.14%. The complication rate
      according to Clavien grading system was 40.1%. The final stone clearance rates
      were 93.9, 85.71, 90.47, and 77.77% in GSS I, II, III, and IV, respectively
      (p<0.001, <0.05, <0.05 and >0.05, respectively). The Clavien complication rates
      were 23, 61, 52, and 77.7% in GSS I, II, III, and IV, respectively (p<0.001). The
      GSS is a simple and easily reproducible system to preoperatively predict stone
      free rate and perioperative complication rate. It helps in better patient
      counseling preoperatively.

PMID- 25850963
TI  - Facile Self-Assembly of Metallo-Supramolecular Ring-in-Ring and Spiderweb
      Structures Using Multivalent Terpyridine Ligands.
AB  - A series of metallo-supramolecular ring-in-ring structures was generated by
      assembling Cd(II) ions and the multivalent terpyridine ligands (L(1-3)) composed
      of one 60 degrees -bent and two 120 degrees -bent bis(terpyridine)s with varying
      alkyl linker lengths. The mechanistic study for the self-assembly process
      excluded an entropically templated pathway and showed that the intramolecularly
      complexed species is the key intermediate leading to ring-in-ring formation. The
      next-generation superstructure, a spiderweb, was produced in quantitative yield
      using the elongated decakis(terpyridine) ligand (L(5)).

PMID- 25850964
TI  - Genetic variants within the TNFRSF1B gene and susceptibility to rheumatoid
      arthritis and response to anti-TNF drugs: a multicenter study.
AB  - BACKGROUND: Recent research suggests that genetic variants in the tumor necrosis
      factor receptor 2 (TNFRSF1B) gene may have an impact on susceptibility to
      rheumatoid arthritis (RA) and drug response. The present population-based case
      control study was carried out to evaluate whether 5 tagging single-nucleotide
      polymorphisms (SNPs) within the TNFRSF1B gene are associated with the risk of RA
      and response to antitumor necrosis factor (TNF) drugs. METHODS: The study
      population included 1412 RA patients and 1225 healthy controls. A subset of 596
      anti-TNF-naive RA patients was selected to assess the association of TNFRSF1B
      SNPs and drug response according to the EULAR response criteria. RESULTS: We
      found that carriers of the TNFRSF1Brs3397C allele had a significantly increased
      risk of developing RA (P=0.0006). Importantly, this association remained
      significant after correction for multiple testing. We also confirmed the lack of
      association of the TNFRSF1Brs1061622 SNP with the risk of RA in the single-SNP
      analysis (P=0.89), but also through well-powered meta-analyses (PDOM=0.67 and
      PREC=0.37, respectively). In addition, our study showed that carriers of the
      TNFRSF1Brs3397C/C, TNFRSF1Brs1061622G/G, and TNFRSF1Brs1061631A/A genotypes had
      an increased risk of having a worse response to anti-TNF drugs at the level of P
      less than 0.05 (P=0.014, 0.0085 and 0.028, respectively). We also observed that,
      according to a log-additive model, carriers of the TNFRSF1Brs3397C or
      TNFRSF1Brs1061622G alleles showed an increased risk of having worse response to
      anti-TNF medications (P=0.018 and 0.0059). However, the association of the
      TNFRSF1Brs1061622 SNP only reached marginal significance after correction for
      multiple testing according to a log-additive model (P=0.0059) and it was not
      confirmed through a meta-analysis (PDOM=0.12). CONCLUSION: Our results suggest
      that the TNFRSF1Brs3397 variant may play a role in modulating the risk of RA, but
      does not provide strong evidence of an impact of TNFRSF1B variants in determining
      response to anti-TNF drugs.

PMID- 25850965
TI  - Lethal toxicity after administration of azacytidine: implication of the cytidine
      deaminase-deficiency syndrome.
AB  - Azacytidine, an antimetabolite with an original epigenetic mechanism of action,
      increases survival in patients diagnosed with high-risk myelodysplasic syndromes
      or acute myeloid leukemia with less than 30% medullar blasts. Azacytidine is a
      pyrimidine derivative that undergoes metabolic detoxification driven by cytidine
      deaminase (CDA), a liver enzyme whose gene is prone to genetic polymorphism,
      leading to erratic activity among patients. Clinical reports have shown that
      patients with the poor metabolizer (PM) phenotype are likely to experience early
      severe or lethal toxicities when treated with nucleosidic analogs such as
      gemcitabine or cytarabine. No clinical data have been available thus far on the
      relationships between CDA PM status and toxicities in azacytidine-treated
      patients. Here, we measured CDA activity in a case of severe toxicities with
      fatal outcome in a patient undergoing standard azacytidine treatment. Results
      showed that the patient was PM (i.e. residual activity reduced by 63%), thus
      suggesting that an impaired detoxification step could have given rise to the
      lethal toxicities observed. This case report calls for further prospective
      studies investigating the exact role that CDA status plays in the clinical
      outcome of patients treated with azacytidine. 

PMID- 25850967
TI  - An empirical investigation of suicide schemas in individuals with Posttraumatic
      Stress Disorder.
AB  - Posttraumatic Stress Disorder (PTSD) has been strongly associated with
      suicidality. Despite the growing evidence suggesting that suicidality is
      heightened by the presence of an elaborated suicide schema, investigations of
      suicide schemas are sparse. Using novel methodologies, this study aimed to
      compare the suicide schema of PTSD individuals with and without suicidal ideation
      in the past year. Fifty-six participants with a diagnosis of PTSD (confirmed via
      the Clinician Administered PTSD Scale) completed questionnaires to assess
      suicidality, depressive severity and hopelessness. A series of direct and
      indirect cognitive tasks were used to assess suicide schemas. The pathfinder
      technique was employed to construct graphical representations of the groups'
      suicide schemas. The suicidal group reported significantly more severe PTSD
      symptoms, depressive symptoms, hopelessness and suicidality. The suicide schema
      of the suicidal group was significantly more extensive compared to the non
      suicidal group even after taking into account in the analyses group differences
      in clinical measures. Moreover, the suicide schemas of the two groups were
      qualitatively distinct from each other. These findings provide support for
      contemporary theories of suicide which view suicide schemas as an important
      indicator of suicide risk. The investigation of schema constructs opens a new
      avenue of research for understanding suicide. 

PMID- 25850966
TI  - Genetic variation of the dopamine transporter (DAT1) influences the acute
      subjective responses to cocaine in volunteers with cocaine use disorders.
AB  - OBJECTIVE: The aim of this study was to identify gene variants of DAT1 (SLC6A3)
      that modulate subjective responses to acute cocaine exposure. METHODS: Non
      treatment-seeking volunteers (n=66) with cocaine use disorders received a single
      bolus infusion of saline and cocaine (40 mg, intravenous) in a randomized order.
      Subjective effects were assessed with visual analog scales administered before (
      15 min) and up to 20 min after infusion. Ratings of subjective effects were
      normalized to baseline, and saline infusion values were subtracted. Data were
      analyzed using repeated measures analysis of variance. DNA from the participants
      was genotyped for the DAT1 intron 8 (rs3836790) and 3'-untranslated region
      (rs28363170) variable number of tandem repeats. RESULTS: Participants were mostly
      male (~80%) and African American (~70%). No differences were found among drug use
      variables between groups for either polymorphism. Carriers of the 9-allele of the
      DAT1 3'-untranslated region (9,9 and 9,10) exhibited greater responses to cocaine
      for 'high', 'any drug effect', 'anxious', and 'stimulated' (all P-values<0.001)
      compared with individuals homozygous for the 10-allele. For the intron 8
      polymorphism, individuals homozygous for the 6-allele exhibited greater responses
      for 'anxious' compared with carriers of the 5-allele (P<0.001). Individuals
      possessing the genotype pattern of 10,10 and at least one 5-allele reported lower
      responses to 'good effects', 'bad effects', 'depressed', and 'anxious' (all P
      values<0.01). CONCLUSION: The data presented here show for the first time support
      for the hypothesis that genetic differences in DAT1 contribute to the variation
      in subjective responses to cocaine among participants with cocaine use disorders.

PMID- 25850968
TI  - Long-term efficacy of sitagliptin as either monotherapy or add-on therapy to
      metformin: improvement in glycemic control over 2 years in patients with type 2
      diabetes.
AB  - OBJECTIVE: To evaluate the efficacy of once daily sitagliptin 100 mg as
      monotherapy or as add-on to metformin in patients with type 2 diabetes mellitus
      (T2DM) over 2 years of treatment. RESEARCH DESIGN AND METHODS: The monotherapy
      analysis used pooled 104 week data from 64 patients in two randomized, double
      blind trials evaluating the safety and efficacy of sitagliptin monotherapy. Data
      used were from patients who were randomized to sitagliptin 100 mg/day, were not
      on an antihyperglycemic agent at the screening visit, had baseline A1C of 7.0%
      10.0%, and had Week 104 A1C measurements. The add-on to metformin analysis used
      pooled data from 347 patients in two randomized double-blind trials evaluating
      the safety and efficacy of sitagliptin + metformin combination therapy. Data used
      were from patients who were randomized to sitagliptin 100 mg/day + metformin
      >=1500 mg/day, had baseline A1C of 7%-10%, and had Week 104 A1C measurements.
      Excluded from either analysis were patients who discontinued prior to 2 years
      (e.g., due to lack of efficacy, a need for rescue medications, or adverse
      experiences). Analysis endpoints were A1C, fasting plasma glucose (FPG), HOMA
      beta, proinsulin/insulin (P/I) ratio, and for monotherapy, 2 hour post-meal
      plasma glucose (PMG). RESULTS: For the pooled monotherapy cohort, after 2 years
      of treatment, mean A1C, FPG, and 2 hour PMG decreased from baseline values of
      7.9%, 156 mg/dL, and 223 mg/dL to 6.9%, 143 mg/dL, and 191 mg/dL, respectively,
      while HOMA-beta increased from 67% to 85% and P/I ratio improved from 0.57 to
      0.28. For the pooled add-on to metformin cohort, after 2 years of treatment, mean
      A1C and FPG decreased from baseline values of 7.7% and 160 mg/dL to 6.9% and 140
      mg/dL, respectively, while HOMA-beta increased from 50% to 62% and P/I ratio
      improved from 0.33 to 0.28. These analyses are limited in that only patients who
      were able to complete 104 weeks of study were included. CONCLUSION: In the subset
      of patients with T2DM who maintained and completed treatment for 2 years with
      sitagliptin as monotherapy or as add-on to metformin, improvements in glycemic
      control and measures of beta-cell function were observed over the course of
      treatment.

PMID- 25850969
TI  - Controlled reactivity tuning of metal-functionalized vanadium oxide clusters.
AB  - Controlling the assembly and functionalization of molecular metal oxides [Mx Oy
      ](n-) (M=Mo, W, V) allows the targeted design of functional molecular materials.
      While general methods exist that enable the predetermined functionalization of
      tungstates and molybdates, no such routes are available for molecular vanadium
      oxides. Controlled design of polyoxovanadates, however, would provide highly
      active materials for energy conversion, (photo-) catalysis, molecular magnetism,
      and materials science. To this end, a new approach has been developed that allows
      the reactivity tuning of vanadium oxide clusters by selective metal
      functionalization. Organic, hydrogen-bonding cations, for example,
      dimethylammonium are used as molecular placeholders to block metal binding sites
      within vanadate cluster shells. Stepwise replacement of the placeholder cations
      with reactive metal cations gives mono- and difunctionalized clusters. Initial
      reactivity studies illustrate the tunability of the magnetic, redox, and
      catalytic activity. 

PMID- 25850970
TI  - Analysis of 24-Hour IOP-related Pattern Changes After Medical Therapy.

PMID- 25850971
TI  - Estimated intakes of brominated flame retardants via diet and dust compared to
      internal concentrations in a Swedish mother-toddler cohort.
AB  - Tri-decabrominated diphenyl ethers (tri-decaBDEs), isomer-specific
      hexabromocyclododecanes (HBCDs) and 14 emerging brominated flame retardants
      (EBFRs) were determined in Swedish market basket samples, two pooled breast milk
      samples and house dust collected in homes of first-time mothers. Daily dietary
      and dust intakes were estimated for the mothers and their toddlers and compared
      to previously reported levels in serum of both the mothers and toddlers and in
      feces of the toddlers (n=20). Diet was the main contributor for intake of
      SigmapentaBDE and alpha-tetrabromoethylcyclohexane (DBE-DBCH) for both mothers
      and toddlers. For SigmaoctaBDE, SigmaHBCD and pentabromobenzene (PBBz), dietary
      intake was more important for mothers while house dust ingestion was more
      important for toddlers. House dust was the main exposure route for SigmadecaBDE,
      decabromodiphenyl ethane (DBDPE), 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EH
      TBB), bis(2-ethylhexyl)tetrabromophthalate (BEH-TEBP), bis(2,4,6-tribromophenoxy)
      ethane (BTBPE) and pentabromotoluene (PBT) for both mothers and toddlers.
      Significant correlations (Spearmans, alpha<0.05) were found between the mothers'
      BDE serum concentrations and their consumption of meat and fish while no
      correlations were found between BFR dietary intake and serum or feces
      concentrations in toddlers. Octa-decaBDE congener concentrations in serum and
      feces of toddlers were significantly correlated to those in house dust. BDE-207
      and -208 concentrations in serum of mothers were significantly correlated with
      the nonaBDEs in house dust. The correlations between house dust and internal
      concentrations and comparison of the house dust and dietary contributions to the
      estimated daily intakes suggest that dust exposure plays a larger role for the
      octa-decaBDE body burden in toddlers than in their mothers.

PMID- 25850972
TI  - Repeatability, ephemerality and inconvenient truths in the speciation process.
AB  - Everyone appreciates the happy fiction that species conform to the simple
      theoretical convenience of a single panmictic population. In speciation genetics,
      a further standard simplification is that it is only those genetic differences
      that are fixed between diverging populations that need concern us in order to
      understand the accumulation of intrinsic barriers to reproduction. To a first
      approximation, of course, both of these assumptions are appropriate and theory
      based on them provides compelling insights into diverse evolutionary phenomena
      (Orr & Turelli ). But what else can we learn about the begetting of biodiversity,
      speciation, by considering explicitly some less convenient realities of natural
      populations? Specifically, how does genetic variation at incompatibility loci
      within a species influence interspecies hybridization upon secondary contact?
      And, in nature, how repeatable among distinct bouts of secondary contact are the
      genomic outcomes of hybridization? Mandeville et al. () tackle exactly this
      question in their new study in Molecular Ecology on five species of suckers, fish
      of the genus Catostomus, that overlap sympatrically in different portions of
      their subdivided ranges that occupy different rivers. They document substantial
      genomic heterogeneity in realized hybridization in nature, both among species
      pairs and among the source populations for hybrids of a given species pair. This
      imperfect repeatability of episodes of hybridization implies greater permeability
      of species barriers in some parts of their range, with intriguing consequences
      for how the integrity of species as independently evolving units could be
      susceptible to collapse. 

PMID- 25850973
TI  - Arrow physicians: are economics and medicine philosophically incompatible?
AB  - Economics is en route to its further expansion in medicine, but many in the
      medical community remain unconvinced that its impact will be positive. Thus, a
      philosophical enquiry into the compatibility of economics and medicine is
      necessary to resolve the disagreements. The fundamental mission of medicine
      obliges physicians to practise science and compassion to serve the patient's best
      interests. Conventional (neoclassical) economics assumes that individuals are
      self-interested and that competitive markets will emerge optimal states.
      Economics is seemingly incompatible with the emphasis of putting patients'
      interests first. This idea is refuted by Professor Kenneth Arrow's health
      economics seminal paper. Arrow emphasizes that medical practice involves agency,
      knowledge, trust and professionalism, and physician-patient relation critically
      affects care quality. The term Arrow Physician is used to mean a humanistic carer
      who has a concern for the patient and acts on the best available evidence with
      health equity in mind. To make this practice sustainable, implementing
      appropriate motivations, constitutions and institutions to enable altruistic
      agency is critical. There is substantial evidence that polycentric governance can
      encourage building trust and reciprocity, so as to avoid depletion of communal
      resources. This paper proposes building trusting institutions through granting
      altruistic physicians adequate autonomy to direct resources based on patients'
      technical needs. It also summarizes the philosophy bases of medicine and
      economics. It, therefore, contributes to developing a shared language to
      facilitate intellectual dialogues, and will encourage trans-disciplinary research
      into medical practice. This should lead to medicine being reoriented to care for
      whole persons again.

PMID- 25850974
TI  - Environmental factors contribute to the formation and maintenance of the contact
      zone observed in deciduous broad-leaved tree species in Japan.
AB  - Contact zones are defined as areas where populations from different refugia meet
      during a postglacial expansion and distinct DNA lineages are mixedly distributed.
      In Japan, contact zones of various plants and animals were reported from the
      Kinki-Chugoku region. These contact zones appear to be maintained without any
      drastic topographic barriers such as those observed in the Alps and Pyrenees
      Mountains. In this study, the mechanisms underlying the formation and/or
      maintenance of these contact zones were investigated using six deciduous broad
      leaved tree species (Carpinus laxiflora, C. tschonoskii, C. japonica, Magnolia
      obovata, Padus grayana, and Euonymus oxyphyllus). First, the precise location of
      the contact zones was examined by intensive genetic analysis of the six species.
      Second, the relationships between the geographic location of the contact zone and
      various environmental factors, including climate and topography, were
      investigated by generalized additive models to reveal the mechanisms of the
      formation and maintenance of the contact zones. As a result, four of the six
      examined plant species clearly showed a geographically common contact zone in
      Hyogo Prefecture and its adjacent areas. The results of the generalized additive
      models indicate that the pattern of low habitat suitability estimated by
      ecological niche modeling was the most important factor for determining the
      location of the common contact zone. These results suggest that areas with low
      habitat suitability in Hyogo Prefecture restrict the migration and gene flow of
      the four species in this region, and thus, they maintain the pattern of the
      contact zones. This study suggests that there are major effects of habitat
      suitability on the formation and maintenance of the contact zones. 

PMID- 25850975
TI  - The effects of statins on benign prostatic hyperplasia in elderly patients with
      metabolic syndrome.
AB  - PURPOSE: To evaluate the effects of simvastatin and atorvastatin in elderly male
      patients with benign prostatic hyperplasia (BPH) accompanied by metabolic
      syndrome (MetS). METHODS: Eligible patients aged >60 year with BPH accompanied by
      MetS were randomly assigned to receive 40 mg of simvastatin daily, 20 mg of
      atorvastatin daily or placebo (control group) treatment for 12 months. Serum
      lipids, interleukin 6 (IL-6), high-sensitivity C-reactive protein (hs-CRP),
      prostate-specific antigen, prostate volume (PV) and the International Prostate
      Symptom Score (IPSS) were tested before and after treatment. RESULTS: The levels
      of serum total cholesterol (TC), triglycerides, low-density lipoprotein
      cholesterol, hs-CRP, IL-6 and IPSS was decreased, serum high-density lipoprotein
      cholesterol (HDL-C) was increased, and PV was reduced in the patients following
      treatments with statins. The PV of the patients who received simvastatin were
      reduced more than those of the patients who received atorvastatin. The decrease
      in PV was more significant in the obesity patients than in the normal weight
      patients and in the hyperlipidemia patients than in the normal-lipid patients
      following the statin interventions. The reduction in PV was positively related to
      the decreases in the levels of TC and IL-6 and to the increase in the level of
      HDL-C. CONCLUSIONS: Simvastatin and atorvastatin significantly reduced PV,
      improved lower urinary tract symptoms, and slowed the clinical progression of BPH
      possibly by lowering cholesterol and anti-inflammatory factors.

PMID- 25850976
TI  - Depression and cardiovascular disease.
AB  - There is a wealth of evidence linking depression to increased risk for
      cardiovascular disease (CVD) and worse outcomes among patients with known CVD. In
      addition, there are safe and effective treatments for depression. Despite this,
      depression remains under-recognized and undertreated in patients at risk for or
      living with CVD. In this review, we first summarize the evidence linking
      depression to increased risk of CVD and worse patient outcomes. We then review
      the mechanisms by which depression may contribute to cardiovascular risk and poor
      cardiovascular outcomes. We then summarize prior studies of depression treatment
      on cardiovascular outcomes. Finally, we offer guidance in the identification and
      management of depression among CVD populations. Given that 1 in 4 CVD patients
      has concurrent depression, application of these best-practices will assist
      providers in achieving optimal outcomes for their CVD patients. 

PMID- 25850977
TI  - Determining pathogenicity in cardiac genetic testing: Filling in the blank
      spaces.

PMID- 25850978
TI  - Recent findings of long-chain n-3 polyunsaturated fatty acids (LCn-3 PUFAs) on
      atherosclerosis and coronary heart disease (CHD) contrasting studies in Western
      countries to Japan.
AB  - Recent long-term randomized clinical trials (RCTs) of long-chain n-3
      polyunsaturated fatty acids (LCn-3 PUFAs) on coronary heart disease (CHD) among
      high-risk patients conducted in Western countries all failed to show their
      clinical benefits. In striking contrast, an RCT of LCn-3 PUFAs on CHD conducted
      in Japan, which is a combination of secondary and primary prevention, showed a
      significant 19% reduction. Potential reasons for this discrepancy are large
      differences in doses of LCn-3 PUFAs administered (300-900 mg/day in Western
      countries vs. 1800 mg/day in Japan) and background dietary intake of LCn-3 PUFAs
      (<300 mg/day in Western countries vs. >1000 mg/day in Japan). These observations
      suggest that higher doses of LCn-3 PUFAs than examined in RCTs in Western
      countries may be cardio-protective. Atherosclerosis is the major underlying cause
      of CHD. Recent observational studies and an RCT of LCn-3 PUFAs on atherosclerosis
      in Japan show that LCn-3 PUFAs are anti-atherogenic. In this brief review, we
      focus on recent epidemiological and clinical findings of LCn-3 PUFAs on
      atherosclerosis and CHD, contrasting studies in Western countries to those in
      Japan. We also discuss mechanisms of high-dose LCn-3 PUFAs on atherosclerosis.

PMID- 25850979
TI  - Biological pacemakers: Ready for the clinic?

PMID- 25850980
TI  - Fast GPU-based computation of spatial multigrid multiframe LMEM for PET.
AB  - Significant efforts were invested during the last decade to accelerate PET list
      mode reconstructions, notably with GPU devices. However, the computation time per
      event is still relatively long, and the list-mode efficiency on the GPU is well
      below the histogram-mode efficiency. Since list-mode data are not arranged in any
      regular pattern, costly accesses to the GPU global memory can hardly be optimized
      and geometrical symmetries cannot be used. To overcome obstacles that limit the
      acceleration of reconstruction from list-mode on the GPU, a multigrid and
      multiframe approach of an expectation-maximization algorithm was developed. The
      reconstruction process is started during data acquisition, and calculations are
      executed concurrently on the GPU and the CPU, while the system matrix is computed
      on-the-fly. A new convergence criterion also was introduced, which is
      computationally more efficient on the GPU. The implementation was tested on a
      Tesla C2050 GPU device for a Gemini GXL PET system geometry. The results show
      that the proposed algorithm (multigrid and multiframe list-mode expectation
      maximization, MGMF-LMEM) converges to the same solution as the LMEM algorithm
      more than three times faster. The execution time of the MGMF-LMEM algorithm was
      1.1 s per million of events on the Tesla C2050 hardware used, for a reconstructed
      space of 188 x 188 x 57 voxels of 2 x 2 x 3.15 mm3. For 17- and 22-mm simulated
      hot lesions, the MGMF-LMEM algorithm led on the first iteration to contrast
      recovery coefficients (CRC) of more than 75 % of the maximum CRC while achieving
      a minimum in the relative mean square error. Therefore, the MGMF-LMEM algorithm
      can be used as a one-pass method to perform real-time reconstructions for low
      count acquisitions, as in list-mode gated studies. The computation time for one
      iteration and 60 millions of events was approximately 66 s.

PMID- 25850981
TI  - Multi-patient finite element simulation of keeled versus pegged glenoid implant
      designs in shoulder arthroplasty.
AB  - This study investigates the mechanical behaviour of keeled and pegged implant
      designs used in shoulder arthroplasty for the first time using multiple 3D
      models. Thus, this study should provide valuable insights into the preferable use
      of either of these two controversial implant designs. Three-dimensional models of
      a scapula were derived from the CT scans of five patients, and an inter-patient
      specific finite element analysis with special attention to bone density and
      boundary conditions was carried out. A distinct decrease in the investigated
      parameters was evident with the pegged implant in all of the patients,
      specifically for the implant and the bone cement. The relevance of the stress
      reduction within the bone is minor, whereas the reduction in the stress of the
      bone cement contributes to an increase in the bone cement survival. The
      particular construction of the pegged implant provides better stability and
      therefore supports bone ingrowth. The large variations between the patients show
      the necessity of patient-specific simulations and the use of multiple models to
      derive valuable results. In the conducted inter-patient-specific FEA, the pegged
      glenoid implants were found to exhibit superior behaviour compared with keeled
      implants. The results confirm the general clinical findings and demonstrate the
      FEA as a valuable tool in prosthetic and orthopaedic problems. 

PMID- 25850982
TI  - Continuous-wavelet-transform analysis of the multifocal ERG waveform in glaucoma
      diagnosis.
AB  - The vast majority of multifocal electroretinogram (mfERG) signal analyses to
      detect glaucoma study the signals' amplitudes and latencies. The purpose of this
      paper is to investigate application of wavelet analysis of mfERG signals in
      diagnosis of glaucoma. This analysis method applies the continuous wavelet
      transform (CWT) to the signals, using the real Morlet wavelet. CWT coefficients
      resulting from the scale of maximum correlation are used as inputs to a neural
      network, which acts as a classifier. mfERG recordings are taken from the eyes of
      47 subjects diagnosed with chronic open-angle glaucoma and from those of 24
      healthy subjects. The high sensitivity in the classification (0.894) provides
      reliable detection of glaucomatous sectors, while the specificity achieved
      (0.844) reflects accurate detection of healthy sectors. The results obtained in
      this paper improve on the previous findings reported by the authors using the
      same visual stimuli and database.

PMID- 25850983
TI  - Strength analysis of clavicle fracture fixation devices and fixation techniques
      using finite element analysis with musculoskeletal force input.
AB  - In the cases, when clavicle fractures are treated with a fixation plate, opinions
      are divided about the best position of the plate, type of plate and type of screw
      units. Results from biomechanical studies of clavicle fixation devices are
      contradictory, probably partly because of simplified and varying load cases used
      in different studies. The anatomy of the shoulder region is complex, which makes
      it difficult and expensive to perform realistic experimental tests; hence,
      reliable simulation is an important complement to experimental tests. In this
      study, a method for finite element simulations of stresses in the clavicle plate
      and bone is used, in which muscle and ligament force data are imported from a
      multibody musculoskeletal model. The stress distribution in two different
      commercial plates, superior and anterior plating position and fixation including
      using a lag screw in the fracture gap or not, was compared. Looking at the
      clavicle fixation from a mechanical point of view, the results indicate that it
      is a major benefit to use a lag screw to fixate the fracture. The anterior
      plating position resulted in lower stresses in the plate, and the anatomically
      shaped plate is more stress resistant and stable than a regular reconstruction
      plate. 

PMID- 25850984
TI  - Stress distribution in a premolar 3D model with anisotropic and isotropic enamel.
AB  - The aim of this study was to compare the areas of stress concentration in a three
      dimensional (3D) premolar tooth model with anisotropic or isotropic enamel using
      the finite element method. A computed tomography was imported to an image
      processing program to create the tooth model which was exported to a 3D modeling
      program. The mechanical properties and loading conditions were prescribed in
      Abaqus. In order to evaluate stresses, axial and oblique loads were applied
      simulating realistic conditions. Compression stress was observed on the side of
      load application, and tensile stress was observed on the opposite side. Tensile
      stress was concentrated mainly in the cervical region and in the alveolar
      insertion bone. Although stress concentration analyses of the isotropic 3D models
      produced similar stress distribution results when compared to the anisotropic
      models, tensile stress values shown by anisotropic models were smaller than the
      isotropic models. Oblique loads resulted in higher values of tensile stresses,
      which concentrate mainly in the cervical area of the tooth and in the alveolar
      bone insertion. Anisotropic properties must be utilized in enamel stress
      evaluation in non-carious cervical lesions. 

PMID- 25850986
TI  - beta-Octakis(methylthio)porphycenes: synthesis, characterisation and third order
      nonlinear optical studies.
AB  - A novel electron deficient beta-octakis(methylthio)porphycene, along with its
      Zn(ii) and Ni(ii) derivatives, was synthesized for the first time. The
      macrocyclic structure exhibits core ruffling with a largely red shifted
      absorption band (~750 nm) and also a large enhancement in the third order
      nonlinear optical response. 

PMID- 25850985
TI  - Performance investigation of SP3 and diffusion approximation for three
      dimensional whole-body optical imaging of small animals.
AB  - The third-order simplified harmonic spherical approximation (SP3) and diffusion
      approximation (DA) equations have been widely used in the three-dimensional (3D)
      whole-body optical imaging of small animals. With different types of tissues,
      which were classified by the ratio of u s'/u alpha, the two equations have their
      own application scopes. However, the classification criterion was blurring and
      unreasonable, and the scope has not been systematically investigated until now.
      In this study, a new criterion for classifying tissues was established based on
      the absolute value of absorption and reduced scattering coefficients. Using the
      newly defined classification criterion, the performance and applicability of the
      SP3 and DA equations were evaluated with a series of investigation experiments.
      Extensive investigation results showed that the SP3 equation exhibited a better
      performance and wider applicability than the DA one in most of the observed
      cases, especially in tissues of low-scattering-low-absorption and low-scattering
      high-absorption range. For the case of tissues with the high-scattering-low
      absorption properties, a similar performance was observed for both the SP3 and
      the DA equations, in which case the DA was the preferred option for 3D whole-body
      optical imaging. Results of this study would provide significant reference for
      the study of hybrid light transport models. 

PMID- 25850987
TI  - Pharmacokinetics and pharmacodynamics of continuous infusion meropenem in
      overweight, obese, and morbidly obese patients with stable and unstable kidney
      function: a step toward dose optimization for the treatment of severe gram
      negative bacterial infections.
AB  - BACKGROUND: Meropenem is an anti-Gram-negative antimicrobial, the time-dependent
      activity of which may be maximized through administration by continuous infusion.
      OBJECTIVES: The objectives of this study were to characterize the
      pharmacokinetics of continuous infusion meropenem in relation to body size and
      Cockcroft-Gault estimated creatinine clearance (CLCR) in overweight and obese
      patients with stable and unstable kidney function with the intent of creating a
      nomogram for optimal dosing. PATIENTS AND METHODS: Patients from a single
      institution with a body mass index >=25 kg/m(2) receiving meropenem by continuous
      infusion with measurement of meropenem steady-state concentrations (C ss) were
      identified. Individual Bayesian estimates of meropenem volume of distribution of
      the central compartment (V c) and clearance (CL) were calculated and
      relationships to body size descriptors and CLCR estimated using these body size
      descriptors were defined by regression. Kidney function stability was defined
      based on median absolute deviation, stratification by the ratio of maximum to
      minimum serum creatinine (SCr) and individual patient-level regression of SCr
      over time. The influence of kidney function stability on meropenem CL estimation
      by CLCR was tested. RESULTS: A total of 375 patients (77.9 % male) with 846 C ss
      values (62.4 % of patients with >=2 measurements) were identified. The median
      daily dose of meropenem and frequency of infusion bag changes were 2000 mg/day
      and four times per day, respectively. The meropenem C ss values were >=16, >=8,
      >=4, and >=2 mg/L for 41.1, 76.1, 97.4, and 99.9 % of observations, respectively.
      The median (range) age, weight, and BMI were 66 (24-90) years, 90 (70-250) kg,
      and 30.8 (25.1-81.6) kg/m(2), respectively. The mean [standard deviation (SD)]
      serum creatinine at baseline was 1.57 (1.37) mg/dL. The mean (SD) V c was 28.1
      (1.36) L and not related to body size, while CL was 8.85 (6.40) L/h and best
      related to CLCR estimated using adjusted body weight (ABW). The meropenem CL to
      CLCR relationship was not significantly impacted by the presence or absence of
      kidney function stability. The user-friendly dosing nomogram based on CLCR
      estimated using ABW showed that optimal drug exposure [Css >= minimum inhibitory
      concentration (MIC)] may be obtained even against multi-drug resistant (MDR)
      pathogens when considering dosages up to 1250 mg every 6 h by continuous
      infusion. CONCLUSIONS: Meropenem CL is best estimated using CLCR with ABW in
      patients with a BMI >=25 kg/m(2) and this relationship is not altered by unstable
      kidney function. Application of our dosing nomogram may improve the care of
      overweight and obese patients with severe MDR Gram-negative infections treated
      with meropenem by continuous infusion.

PMID- 25850988
TI  - Immunoregulatory cytokine networks: 60 years of learning from murine
      cytomegalovirus.
AB  - Innate immunity defends against infection but also mediates immunoregulatory
      effects shaping innate and adaptive responses. Studies of murine cytomegalovirus
      (MCMV) infections have helped elucidate the mechanisms inducing, as well as the
      elicited soluble and cellular networks contributing to, innate immunity.
      Specialized receptors are engaged by infection-induced structures to stimulate
      production of key innate cytokines. These then stimulate cytokine and cellular
      responses such as activation of natural killer (NK) cells to mediate elevated
      killing by type 1 interferon (IFN) and/or to produce the pro-inflammatory and
      antiviral cytokine IFN-gamma by interleukin 12 (IL-12). An inter-systemic loop,
      with IL-6 inducing glucocorticoid release, negatively regulates these early
      cytokine responses. As infections advance into periods of overlapping innate and
      adaptive responses, however, the cells are intrinsically conditioned to modify
      the biological effects of exposure to individual cytokines. Some pathways are
      turned off to inhibit an existing, whereas others are broadened for acquisition
      of a new, response function. Remarkably, extended NK cell proliferation during
      MCMV infection is associated with epigenetic modifications shifting the state of
      the inhibitory cytokine IL-10 gene from closed to open and results in their
      becoming equipped to produce this cytokine. When induced, NK cell IL-10
      negatively regulates the magnitude of adaptive responses to protect against
      immune pathology. Thus, innate immunoregulatory cytokine networks are integral to
      pro-inflammatory and defense functions, but responding cells have the flexibility
      to undergo cell intrinsic conditioning with changing network characteristics to
      result in a new negative immunoregulatory function, and consequently, both
      promote beneficial and limit detrimental immune responses. 

PMID- 25850990
TI  - Measuring coral size-frequency distribution using stereo video technology, a
      comparison with in situ measurements.
AB  - Coral colony size-frequency distribution data offer valuable information about
      the ecological status of coral reefs. Such data are usually collected by divers
      in situ, but stereo video is being increasingly used for monitoring benthic
      marine communities and may be used to collect size information for coral
      colonies. This study compared the size-frequency distributions of coral colonies
      obtained by divers measuring colonies 'in situ' with digital video imagery
      collected using stereo video and later processed using computer software. The
      size-frequency distributions of the two methods were similar for corymbose
      colonies, although distributions were different for massive, branching and all
      colonies combined. The differences are mainly driven by greater abundance of
      colonies >50 cm and fewer colonies <10 cm recorded when using the in situ method.
      The stereo video method detected 93% of marked colonies >5 cm and was able to
      record measurements on 87% of the colonies detected. However, stereo video only
      detected 57% of marked colonies <5 cm, suggesting that this method may be
      unsuitable for assessing abundance of coral recruits. Estimates of colony size
      made with the stereo video were smaller than the in situ technique for all growth
      forms, particularly for massive morphologies. Despite differences in size
      distributions, community assessments, which incorporated genera, growth forms and
      size, were similar between the two techniques. Stereo video is suitable for
      monitoring coral community demographics and provided data similar to in situ
      measure for corymbose corals, but the ability to accurately measure massive and
      branching coral morphologies appeared to decline with increasing colony size.

PMID- 25850989
TI  - An endocytic YXXPhi (YRRF) cargo sorting motif in the cytoplasmic tail of murine
      cytomegalovirus AP2 'adapter adapter' protein m04/gp34 antagonizes virus evasion
      of natural killer cells.
AB  - Viruses have evolved proteins that bind immunologically relevant cargo molecules
      at the cell surface for their downmodulation by internalization. Via a tyrosine
      based sorting motif YXXPhi in their cytoplasmic tails, they link the bound cargo
      to the cellular adapter protein-2 (AP2), thereby sorting it into clathrin
      triskelion-coated pits for accelerated endocytosis. Downmodulation of CD4
      molecules by lentiviral protein NEF represents the most prominent example. Based
      on connecting cargo to cellular adapter molecules, such specialized viral
      proteins have been referred to as 'connectors' or 'adapter adapters.' Murine
      cytomegalovirus glycoprotein m04/gp34 binds stably to MHC class-I (MHC-I)
      molecules and suspiciously carries a canonical YXXPhi endocytosis motif YRRF in
      its cytoplasmic tail. Disconnection from AP2 by motif mutation ARRF should retain
      m04-MHC-I complexes at the cell surface and result in an enhanced silencing of
      natural killer (NK) cells, which recognize them via inhibitory receptors. We have
      tested this prediction with a recombinant virus in which the AP2 motif is
      selectively destroyed by point mutation Y248A, and compared this with the
      deletion of the complete protein in a Deltam04 mutant. Phenotypes were
      antithetical in that loss of AP2-binding enhanced NK cell silencing, whereas
      absence of m04-MHC-I released them from silencing. We thus conclude that AP2
      binding antagonizes NK cell silencing by enhancing endocytosis of the inhibitory
      ligand m04-MHC-I. Based on a screen for tyrosine-based endocytic motifs in
      cytoplasmic tail sequences, we propose here the new hypothesis that most proteins
      of the m02-m16 gene family serve as 'adapter adapters,' each selecting its
      specific cell surface cargo for clathrin-assisted internalization. 

PMID- 25850991
TI  - Mercury in the blue tilapia Oreochromis aureus from a dam located in a mining
      region of NW Mexico: seasonal variation and percentage weekly intake (PWI).
AB  - Uptake of mercury (Hg) through fish consumption is one of the key aspects of the
      Hg cycle in the aquatic ecosystems. In tropical latitudes, biomonitoring of Hg in
      freshwater reservoirs is scarce. The objectives of the study were to determine Hg
      distribution in muscle, liver, and kidney of blue tilapia Oreochromis aureus from
      a dam located in a mining region of northwest Mexico, to define temporal
      variations of Hg concentrations in fish collected during the dry and rainy
      seasons, and to estimate the percentage weekly intake (PWI) of Hg through fish
      consumption considering the individual weekly intake of fish in Mexico and the
      provisional tolerable weekly intake of Hg (5 MUg kg(-1) body weight). The
      sequence of Hg concentrations was liver > kidney > muscle during the rainy season
      and kidney > liver > muscle during the dry season. Levels of Hg were
      significantly higher (p < 0.001) in muscle (0.36 MUg g(-1)) and kidney (0.65 MUg
      g(-1)) of specimens collected during the dry season in comparison to individuals
      collected during the rainy season; accordingly, average PWI in the dry season
      (5.41) was higher than in the rainy season (1.80). Though collected fish were
      adults, Hg levels in the edible portion are not harmful to consumers, even during
      the dry season that Hg levels were higher. 

PMID- 25850992
TI  - Colonization of Legionella species in Turkish baths in hotels in Alanya, Turkey.
AB  - This study evaluated the prevalence of Legionella species in water samples
      collected from Turkish baths in hotels in Alanya, Turkey, from August 2003 to
      September 2013. Water samples were collected in 100-mL sterile containers and
      then concentrated by filtration. Heat treatment was used to eliminate other
      microorganisms from the samples, which were then spread on Legionella-selective
      buffered charcoal yeast extract alpha (BCYE-alpha) agar and on BCYE-alpha agar
      supplemented with glycine, vancomycin, polymyxin, and cycloheximide. Cysteine
      dependent colonies were identified by latex agglutination. In total, 135 samples
      from 52 hotels with Turkish baths were evaluated. Legionella species were
      identified in 11/52 (21.2%) hotels and 18/135 (13.3%) samples. The most
      frequently isolated species was Legionella pneumophila, with most isolates
      belonging to serogroups 6 (55.6%) and 1 (22.2%). The colony count was <100 colony
      forming units (CFU) mL(-1) in nine samples, from 100 to 1000 CFU mL(-1) in six
      samples, and >1000 CFU mL(-1) in three samples. These findings suggest that the
      hot water systems of Turkish baths in hotels must be viewed as a possible source
      of travel-associated Legionnaires' disease, and preventative measures should be
      put in place.

PMID- 25850993
TI  - Distribution and source apportionment of polycyclic aromatic hydrocarbons in the
      surface soil of Baise, China.
AB  - To estimate the distribution and sources of polycyclic aromatic hydrocarbons
      (PAHs) in the soils of Baise, in southwest China, soil sampling sites were
      selected from industry, traffic, rubbish, gas station, residential, and suburban
      areas for analysis of PAHs. The average concentrations of ?16PAHs in the present
      study varied significantly, depending on the sampling location, and ranged from
      16.8 to 6,437.0 MUg/kg (dry weight basis), with a mean value of 565.8 MUg/kg. PAH
      concentrations decreased significantly along the industry-traffic-rubbish-gas
      station-residential-suburban transect. The PAH profiles in the surface soil of
      the different areas imply that either source proximity to the sampling sites, or
      transport and deposition effects influenced PAH distributions. Two diagnostic
      ratios were selected and used to apportion PAH sources in the surface soil, and
      bivariate plots show general trends of covariation. Principal component analysis
      and multivariate linear regression were used to determine the primary sources and
      their contributions of PAHs to the soils. The model showed that factors 1 (coal
      and wood combustion) and 2 (petroleum combustion) contributed over 52.1 and 32.5%
      of the total source of soil PAHs, respectively. The remaining 15.4% came from
      evaporative and uncombusted petroleum.

PMID- 25850994
TI  - What doesn't kill you makes you fat!

PMID- 25850995
TI  - Conservative management of neurocysticercosis in a patient with hematopoietic
      stem cell transplantation: a case report and review.
AB  - Neurocysticercosis, an infection of the central nervous system with the larval
      stage of the cestode Taenia solium, is common in developing countries but its
      occurrence and management in allogeneic hematopoietic stem cell transplantation
      (HSCT) has not been reported previously, to our knowledge. We report the case of
      an immigrant female patient who underwent a matched-related allogeneic HSCT for
      acute lymphoblastic leukemia and was incidentally found to have a solitary viable
      neurocysticercosis lesion. However, despite severe immunosuppression, the size of
      the cyst did not increase. More importantly, restoration of the immune system did
      not induce significant inflammation or seizures. Subsequent follow-up
      demonstrated complete resolution of the neurocysticercosis lesion. Thus, in the
      setting of HSCT, an asymptomatic patient with a single neurocysticercosis lesion
      was successfully managed without the use of anthelmintics, steroids, or anti
      epileptics.

PMID- 25850997
TI  - Interactions between rivaroxaban and antiphospholipid antibodies in thrombotic
      antiphospholipid syndrome.
AB  - INTRODUCTION: Rivaroxaban can affect lupus anticoagulant (LA) testing and
      antiphospholipid antibodies (aPL) may interfere with the anticoagulant action of
      rivaroxaban. AIMS: To establish the influence of rivaroxaban on LA detection and
      of aPL on the anticoagulant action of rivaroxaban. METHODS: Rivaroxaban and 52
      IgG preparations (20 LA+ve, 12 LA-ve thrombotic antiphospholipid syndrome [APS]
      patients, and 20 normal controls [NC]) were spiked into pooled normal plasma
      (PNP) for relevant studies. LA detection was also studied in APS patients
      receiving rivaroxaban 20 mg once daily. RESULTS: In vitro spiking of samples with
      rivaroxaban showed no false positive LA with Textarin time, Taipan venom
      time/Ecarin clotting time (TVT/ECT), dilute prothrombin time (dPT) and in-house
      dilute Russell's viper venom time (DRVVT), but false positives in the majority of
      NC and LA negative IgG with two commercial DRVVT reagents at 250 ng/mL but not 50
      ng/mL rivaroxaban. Ex vivo studies: six LA+ve patients on rivaroxaban remained LA
      positive with TVT/ECT and DRVVT at peak (162-278 ng/mL) and trough (30-85 ng/mL)
      rivaroxaban levels. Six LA-ve patients became (apparently) LA+ve with two DRVVT
      reagents (test/confirm ratio median [confidence interval], 1.6 [1.3-1.8], 1.6
      [1.4-1.9]) but not with TVT/ECT at peak rivaroxaban levels, and remained LA-ve
      with both DRVVT reagents and TVT/ECT at trough levels. aPL positive IgG spiking
      of PNP had no effect on rivaroxaban's anticoagulant action on thrombin generation
      or rivaroxaban anti-Xa levels. CONCLUSIONS: The TVT/ECT ratio and Textarin time
      were not affected even at peak rivaroxaban levels, enabling detection of LA ex
      vivo. aPL had no effects on rivaroxaban's anticoagulant action in vitro.

PMID- 25850996
TI  - Whole exome sequencing identifies driver mutations in asymptomatic computed
      tomography-detected lung cancers with normal karyotype.
AB  - The efficacy of curative surgery for lung cancer could be largely improved by non
      invasive screening programs, which can detect the disease at early stages. We
      previously showed that 18% of screening-identified lung cancers demonstrate a
      normal karyotype and, following high-density genome scanning, can be subdivided
      into samples with 1) numerous; 2) none; and 3) few copy number alterations. Whole
      exome sequencing was applied to the two normal karyotype, screening-detected lung
      cancers, constituting group 2, as well as normal controls. We identified
      mutations in both tumors, including KEAP1 (commonly mutated in lung cancers) in
      one, and TP53, PMS1, and MSH3 (well-characterized DNA-repair genes) in the other.
      The two normal karyotype screening-detected lung tumors displayed a typical lung
      cancer mutational profile that only next generation sequencing could reveal,
      which offered an additional contribution to the over-diagnosis bias concept
      hypothesized within lung cancer screening programs. 

PMID- 25850998
TI  - Is cystic echinoccocosis re-emerging in western Spain?
AB  - Cystic echinococcosis (CE) remains an important health problem in many areas of
      the world, including the Mediterranean region. We performed a retrospective study
      of cases reported from 1998 to 2012 in order to review and update the
      epidemiology of this disease in a highly endemic area situated in western Spain.
      A total of 471 patients were diagnosed with hydatid disease. Of these cases,
      55.8% were male, with an average age of 62.3 +/- 19.5 years. More importantly,
      1.5% of patients were children, and 20.5% were aged <45 years. An active
      therapeutic approach was implemented for 92.6% of the CE patients with primary
      diagnoses; however, a 'watch and wait' strategy was used in 59.3% of all
      secondary CE diagnoses. The incidence rate of hydatid disease was significantly
      higher compared to the incidence described in the Notifiable Disease System in
      this area. Furthermore, a significant decrease in hydatid incidence during the
      years included in the study was observed (beta = -0.4357, P < 0.001). CE
      incidence has diminished in recent years, although active transmission remains in
      paediatric cases. Additionally, CE incidence remains high in our region despite
      public health plans for its control. The documented incidence of CE disease
      clearly underestimates the real numbers. 

PMID- 25851000
TI  - Genome-wide DArT and SNP scan for QTL associated with resistance to stripe rust
      (Puccinia striiformis f. sp. tritici) in elite ICARDA wheat (Triticum aestivum
      L.) germplasm.
AB  - KEY MESSAGE: Identified DArT and SNP markers including a first reported QTL on
      3AS, validated large effect APR on 3BS. The different genes can be used to
      incorporate stripe resistance in cultivated varieties. Stripe rust [yellow rust,
      caused by Puccinia striiformis f. sp. tritici (Pst)] is a serious disease in
      wheat (Triticum aestivum). This study employed genome-wide association mapping
      (GWAM) to identify markers linked to stripe rust resistance genes using Diversity
      Arrays Technology (DArT((r))) and single-nucleotide polymorphism (SNP) Infinium
      9K assays in 200 ICARDA wheat genotypes, phenotyped for seedling and adult plant
      resistance in two sites over two growing seasons in Syria. Only 25.8 % of the
      genotypes showed resistance at seedling stage while about 33 and 44 % showed
      moderate resistance and resistance response, respectively. Mixed-linear model
      adjusted for false discovery rate at p < 0.05 identified 12 DArT and 29 SNP
      markers on chromosome arms 3AS, 3AL, 1AL, 2AL, 2BS, 2BL, 3BS, 3BL, 5BL, 6AL, and
      7DS significantly linked to Pst resistance genes. Of these, the locus on 3AS has
      not been previously reported to confer resistance to stripe rust in wheat. The
      QTL on 3AS, 3AL, 1AL, 2AL, and 2BS were effective at seedling and adult plant
      growth stages while those on 3BS, 3BL, 5BL, 6AL and 7DS were effective at adult
      plant stage. The 3BS QTL was validated in Cham-6 * Cham-8 recombinant inbred line
      population; composite interval analysis identified a stripe resistance QTL
      flanked by the DArT marker, wPt-798970, contributed by Cham-6 parent which
      accounted for 31.2 % of the phenotypic variation. The DArT marker "wPt-798970"
      lies 1.6 cM away from the 3BS QTL detected within GWAM. Epistatic interactions
      were also investigated; only the QTL on 1AL, 3AS and 6AL exhibited interactions
      with other loci. These results suggest that GWAM can be an effective approach for
      identifying and improving resistance to stripe rust in wheat.

PMID- 25851001
TI  - Physical mapping of chromosome 4J of Thinopyrum bessarabicum using gamma
      radiation-induced aberrations.
AB  - KEY MESSAGE: Gamma radiation induced a series of structural aberrations involving
      Thinopyrum bessarabicum chromosome 4J. The aberrations allowed for deletion
      mapping of 101 4J-specific markers and fine mapping of blue-grained gene BaThb.
      Irradiation can induce translocations and deletions to assist physically locating
      genes and markers on chromosomes. In this study, a 12-Gy dosage of (60)Co-gamma
      was applied to pollen and eggs of a wheat (Triticum aestivum) landrace Chinese
      Spring (CS)-Thinopyrum bessarabicum chromosome 4J disomic addition line (DA4J),
      and the gametes from irradiated plants were fertilized with normal CS eggs or
      pollen to produce M1 seeds. Based on genomic in situ hybridization analysis of
      261 M1 plants, we identified 74 lines carrying structural aberrations involving
      chromosome 4J with the higher aberration rate in treated pollen (31.2 %) than in
      the treated eggs (21.3 %). We further identified 43 (53.8 %) lines with
      structural aberrations on chromosome 4J by analyzing another 80 M1 plants with 74
      4J-specific markers, indicating that combining molecular and cytological methods
      was more efficient for detecting chromosome aberrations. Marker analysis thus was
      performed prior to cytogenetic identification on M2-M4 seeds to detect chromosome
      structural aberrations. Sixty-eight M3 lines with structural aberrations on
      chromosome 4J and six previously obtained chromosome 4J alien lines were then
      analyzed using 101 chromosome 4J-specific markers. After combining marker results
      with chromosome aberrations in each line, chromosome 4J was physically divided
      into 24 segmental blocks with 7 in the short arm and 17 in the long arm. The blue
      grained gene BaThb was further mapped into the region corresponding to block 4JL
      11. The chromosome aberrations and the physical map developed in this research
      provide useful stocks and tools for introgression of genes on chromosome 4J into
      wheat.

PMID- 25850999
TI  - Genetics in child and adolescent psychiatry: methodological advances and
      conceptual issues.
AB  - Discovering the genetic basis of early-onset psychiatric disorders has been the
      aim of intensive research during the last decade. We will first selectively
      summarize results of genetic research in child and adolescent psychiatry by using
      examples from different disorders and discuss methodological issues, emerging
      questions and future directions. In the second part of this review, we will focus
      on how to link genetic causes of disorders with physiological pathways, discuss
      the impact of genetic findings on diagnostic systems, prevention and therapeutic
      interventions. Finally we will highlight some ethical aspects connected to
      genetic research in child and adolescent psychiatry. Advances in molecular
      genetic methods have led to insights into the genetic architecture of psychiatric
      disorders, but not yet provided definite pathways to pathophysiology. If
      replicated, promising findings from genetic studies might in some cases lead to
      personalized treatments. On the one hand, knowledge of the genetic basis of
      disorders may influence diagnostic categories. On the other hand, models also
      suggest studying the genetic architecture of psychiatric disorders across
      diagnoses and clinical groups. 

PMID- 25851002
TI  - Genotyping-by-sequencing (GBS) identified SNP tightly linked to QTL for pre
      harvest sprouting resistance.
AB  - KEY MESSAGE: Using a GBS-SNP map, a QTL for pre-harvest sprouting resistance on
      4AL of Totoumai A was delimited to 2.9-cM interval, and SNP closely linked to
      several other QTL were identified. Pre-harvest sprouting (PHS) of wheat is a
      major constraint to wheat production in many wheat-growing areas worldwide,
      because it reduces both wheat grain yield and the end-use quality. To identify
      markers tightly linked to the quantitative trait loci (QTL) for PHS resistance
      and seed dormancy (SD), we evaluated 155 recombinant inbred lines (RIL) derived
      from a cross between a PHS-resistant parent 'Tutoumai A' and a PHS-susceptible
      parent 'Siyang 936' for single-nucleotide polymorphisms (SNP) using genotyping-by
      sequencing (GBS), and for PHS resistance and SD using both field and greenhouse
      grown plants. Two SNP, GBS109947 and GBS212432, were mapped to a major QTL region
      for PHS resistance and SD on chromosome 4AL, and delimited the QTL to a 2.9-cM
      interval. Two and nine additional SNP were mapped to minor QTL regions for SD on
      chromosome 5B and 5A, respectively. Critical SNP in these QTL regions were
      converted into KBioscience Competitive Allele-Specific PCR (KASP) assays that can
      be easily used for marker-assisted selection to improve PHS resistance.

PMID- 25851003
TI  - Commissural region dehiscence from the stent post of Carpentier-Edwards
      bioprosthetic cardiac valves.
AB  - Structural deterioration is the major reason for reoperation in patients with
      valvular bioprostheses. We present findings on a mode of structural
      deterioration, the pathology of which has not yet been well characterized.
      Between January 1990 and December 1992, 39 Carpentier-Edwards standard valves
      (CESTD) and 50 Carpentier-Edwards supra-annular valves (CESAV) were operatively
      removed at St. Paul's Hospital. Of these, 14 bioprostheses (6 CESTD [15%] and 8
      CESAV [16%]) showed dehiscence of a single commissural region from its stent
      post. Age at initial implantation was not significantly different between
      patients with CESAV (52.1 +/- 5.4 years) and CESTD (45.5 +/- 5.1 years, p = ns),
      but time from implantation to reoperation was shorter for CESAV as compared with
      CESTD (7.9 +/- 0.5 vs. 13.3 +/- 0.7 years, respectively, p < 0.01). The vast
      majority (12 14 ) of dehiscences were in mitral bioprostheses, and all patients
      presented with valvular regurgitation. Accompanying structural changes
      (calcification and cuspal tears/perforations), graded semiquantitatively (absent
      = 0, mild = 1, moderate = 2, and severe = 3), ranged from absent to severe in
      individual valves. Radiographically detected calcification was greater in CESTD
      compared with CESAV (CESTD 1.3 +/- 0.3 vs. CESAV 0.5 +/- 0.3, p < 0.05).
      Differences in severity of cuspal tears or perforations were not present. Thus,
      commissural region dehiscence from the stent post of Carpentier-Edwards porcine
      bioprosthetic valves in the mitral position is a relatively common form of
      structural deterioration associated with valvular incompetence. It may occur more
      readily in Carpentier-Edwards supra-annular valves. 

PMID- 25851004
TI  - The encapsulation of polyurethane-insulated transvenous cardiac pacemaker leads.
AB  - When cardiac pacemakers are implanted, the tranvenous route is typically
      preferred. For dual chamber pacemakers, an atrial and a ventricular lead are
      required. Based on postmortem examination of 101 canines with polyurethane
      insulated leads implanted from 10 days through 13 years, encapsulation of these
      leads is initiated by thrombus secondary to endothelial damage and/or blood flow
      perturbations. Organization of thrombus results in a vascularized collagenous
      capsule. With continued blood flow perturbation, more thrombi can form and
      reorganize to cause the collagenous capsules to grow with implant time. Under
      certain conditions, the encapsulating sheath can differentiate into cartilage,
      mineralized tissue, and even bone. The least commonly encapsulated area is in or
      just superior to the annulus of the valve. The most common locations for capsule
      formation are within the upper right atrium (where two leads are often bound
      together by the tissue) and the right ventricle. The ventricular sheaths are
      often adhered firmly to tricuspid valve structures. The presence of relatively
      large, friable, partially organized thrombi on chronic leads is not unusual, even
      after more than 10 years' implantation. It is recommended that chronic leads be
      imaged prior to attempts to remove them to detect the presence and location of
      embolizable structures. 

PMID- 25851005
TI  - AIDS and the heart: Clinicopathologic assessment.
AB  - Acquired immune deficiency syndrome (AIDS) is responsible for significant
      morbidity and mortality in the United States and other countries. Cardiac
      involvement in AIDS, which was previously felt to be an unusual manifestation of
      the disease, is now being described with increasing frequency. Clinical and
      necropsy studies have demonstrated myocarditis, myocardial necrosis,
      cardiomyopathy, pericardial disease, endocarditis, pulmonary hypertension, and
      tumor infiltration in patients dying with AIDS. A direct role for human
      immunodeficiency virus (HIV-1) in the development of myocarditis, myocardopathy,
      and pericardial disease has not yet been elucidated. Recent immunopathological
      evidence suggests a possible role for immune-mediated myocardial inflammatory
      changes. The drugs used to treat HIV-1 have not been shown to be cardiotoxic;
      however, there are suggestions that azidothymidine (AZT) can cause mitochondrial
      changes in myocardial muscle. There are also suggestions that the cardiac
      complications of AIDS are different in patients whose risk factor for HIV
      infection is homosexual practice compared with patients having intravenous drug
      addiction as their major risk factor for HIV disease. Risk factors for myocardial
      disease, other than HIV, may also be contributors to cardiac complications in
      patients with AIDS who are intravenous drug abusers. 

PMID- 25851006
TI  - Myocyte nuclear area as a measure of left ventricular hypertrophy in transplant
      patients.
AB  - Transplanted hearts have been reported to increase in size/weight in the first
      few months after transplant and to remain stable thereafter. An indirect way of
      assessing the changes in heart weight is through the changes in the area of the
      myocyte nucleus (MNA). We studied 20 patients who had undergone orthotopic heart
      transplantation more than 12 months previously; 10 had become hypertensive, and
      the remaining 10 were normotensive. Myocardial biopsies taken the first week
      after transplant and 6, 12, 24, and 52 weeks after transplant were assessed.
      Myocyte nuclear area was measured in 200 myocytes/biopsy with an image analyzer.
      Individual measurements showed a wide variation in MNA, with significant overlaps
      among the different biopsies. Assessment of MNA at one year showed increased MNA
      in 4 10 patients in the hypertensive group and 5 10 in the normotensive group.
      The remaining patients showed either no statistically significant changes in MNA
      or a significant (p < 0.0001) decrease in MNA. The presence of systemic
      hypertension was not a predictive factor for significant hypertrophy and, in some
      cases, not even for hypertrophy itself. We conclude that although there is often
      an increase in MNA of the transplanted heart at one year posttransplant, this
      increase is not systematic, and isolated morphometric results should be viewed
      cautiously. 

PMID- 25851007
TI  - Characteristics of a model of myocardial infarction produced by coronary artery
      ligation in the rat.
AB  - The rat model of coronary artery ligation is widely used to study myocardial
      infarction, ventricular remodeling, and congestive heart failure. Total infarct
      size and the relationship between endocardial and epicardial infarction were
      characterized in 691 animals that survived permanent ligation of the left
      coronary artery. Infarct size was determined from serial histologic sections of
      the left ventricle (LV), followed by planimetry of muscle and scar
      circumferences. Mean infarct size was 34.5% +/- 13.3% of total left ventricular
      circumference. Rats surviving longer durations to terminal study had a smaller
      mean infarct size. Infarct transmurality, as described by the ratio of epicardial
      to-endocardial infarct sizes, was 0.78 +/- 0.01. The transmurality ratio
      increased and its variability decreased as infarct size increased. Subendocardial
      infarcts were more frequent among small infarcts and had smaller areas of
      endocardial infarction. Although infarct size was highly variable, infarct size
      indexed to endocardial infarct size was less variable. Infarct size indexed to
      endocardial infarct size may therefore represent a significantly more powerful
      method for assessing the effects of treatments to reduce infarct size. 

PMID- 25851008
TI  - Contact sites between the inner and outer mitochondrial membranes in stunned
      versus hibernating myocardium.
AB  - This study characterizes the energy state and the influence of calcium on
      myocardial stunning and chronic hibernation via the quantification of a calcium
      sensitive phenomenon known as mitochondrial contact sites. For stunning, the left
      anterior descending artery of mongrel dogs was occluded for 15 minutes, followed
      by a 150-minute reperfusion; for chronic hibernation, we used human biopsies
      obtained during coronary artery bypass graft (CABG) from viable (positron
      emission tomography-controlled) asynergic areas. Both sample groups were
      processed for electron microscopy, and the ratio of surface densities of contact
      sites to mitochondrial membranes was quantified with morphometry. Therefore a
      cycloidal pattern was superimposed on the electron micrographs, and the ratio
      between the total number of intersections between cycloids and contact sites and
      the total number of intersections between cycloids and mitochondrial membranes is
      the ratio of surface densities (Ss). In stunned cells, Ss = 0.46 +/- 0.06, which
      is significantly higher than the ratio in the normokinetic cells, Ss = 0.355 +/-
      0.003, although the general ultrastructure of the subcellular compartments is
      practically identical to those in the normoxic area. The distinction between
      cells affected by chronic hibernation and normal cells was based on structural
      criteria. The ratio of surface densities, expressed Ss = 0.27 +/- 0.05, was
      significantly lower than the ratio in the normoxic area (Ss = 0.356 +/- 0.005).
      The high ratio of surface densities in the stunned cells lends credibility to the
      notion that stunning implies an increased intracellular calcium content and
      energy demand, whereas hibernation might be a kind of low demand-low supply
      situation with a low intracellular calcium level. 

PMID- 25851009
TI  - Beneficial effects of gangliosides on the natural history of acute chagasic
      myocarditis in rats.
AB  - This study was designed to investigate the effects of ganglioside treatment on
      acutely Trypanosoma cruzi-infected rats with emphasis on the heart. Newly weaned
      Wistar rats were infected with T. cruzi (Colombian strain, 50,000 parasites/kg
      body weight injected intraperitoneally). Two groups of 25 infected rats received
      daily injections of saline or ganglioside (10 mg/kg body weight)
      intraperitoneally between the 14th and 30th days after infection. Two groups of
      10 noninfected rats were similarly treated. On day 31, all surviving rats were
      killed. Hearts were collected for histopathology and norepinephrine assay. An
      arbitrary score for myocardial microscopic lesions was used to characterize each
      heart wall. Mortality was recorded throughout the experimental period. Seven of
      25 (28%) ganglioside-treated and 14 of 25 (56%) saline-treated rats died
      spontaneously (p = 0.02). The histological score was 5.4 +/- 3.2 for ganglioside
      treated and 7.9 +/- 3.0 for saline-treated rats (p < 0.05). No difference was
      detected in myocardial norepinephrine content. Thus, ganglioside treatment
      decreases mortality and myocardial inflammation in acute chagasic myocarditis in
      rats. 

PMID- 25851010
TI  - Nonbacterial thrombotic versus infective endocarditis: A necropsy study of 320
      cases.
AB  - The precise relationship between nonbacterial thrombotic endocarditis (NBTE) and
      infective endocarditis (IE) remains to be clearly established, some believing
      that IE might develop from NBTE once the latter becomes secondarily infected
      during bacteremia. To compare the features of the two lesions, 175 cases of NBTE
      and 145 cases of IE encountered in more than 25,000 autopsies performed over a
      period of 24 years (1970-1993) were reviewed, and the relevant clinical,
      pathological, and bacteriological findings assessed. The results show that IE is
      a genuine suppurative infection of cardiac valves ab initio, whereas, in NBTE,
      inflammation is lacking and the lesion is a result of a usually paraneoplastic
      disturbance of thrombosis/thrombolysis. 

PMID- 25851011
TI  - Cholesterol embolization to the coronary arteries resulting in acute myocardial
      infarction: A complication of coronary artery bypass grafting surgery.
AB  - Cholesterol emboli dislodged during coronary artery bypass surgery may be
      released downstream into the native coronary arteries and lead to the development
      of acute myocardial infarction. An autopsy-proven case of such an event occurring
      in a 79-year-old woman illustrates this complication of coronary artery bypass
      surgery. Awareness of this complication by pathologists may facilitate its
      recognition. Awareness by surgeons, on the other hand, may help to prevent it
      through decreased intraoperative manipulation of the involved vessels. 

PMID- 25851012
TI  - Coronary artery intimal hyperplasia, occlusive platelet thrombus, and fatal
      myocardial infarction in an intravenous cocaine user.
AB  - A 38-year-old man died of an acute inferoposterior myocardial infarction, shortly
      after intravenous injection of cocaine. At necropsy, diffuse intimal hyperplasia
      and an occlusive platelet thrombus involved the left main, left anterior
      descending, and the left circumflex coronary arteries. The possible relation of
      these morphologic findings to the effects of cocaine on platelet and coronary
      vascular function are discussed and the relevant literature is reviewed. 

PMID- 25851013
TI  - Cardiac allograft pathology: A comment on the problem of chronic rejection.

PMID- 25851014
TI  - Cardiac allograft pathology-A comment on the problem of chronic rejection.

PMID- 25851015
TI  - Ebstein's malformation.

PMID- 25851016
TI  - Acute humoral rejection.

PMID- 25851017
TI  - Work-related psychosocial risk factors and mental health problems amongst nurses
      at a university hospital in Estonia: a cross-sectional study.
AB  - AIM: Rapid changes in the Estonian health care system have placed extra pressure
      on the nursing profession, but the potential impacts of psychosocial changes have
      not been investigated. We aimed to explore the work-related psychosocial risk
      factors and their relationships with mental health problems (MHPs) amongst nurses
      at the university hospital in Estonia. METHODS: A cross-sectional survey was
      undertaken amongst registered nurses at Tartu University Hospital (TUH).
      Psychosocial work factors and MHPs (stress, somatic symptoms, depressive symptoms
      and burnout) were measured using version two of the Copenhagen Psychosocial
      Questionnaire (COPSOQ II). Descriptive statistics and Pearson's r correlation
      with sequential Bonferroni correction were used to analyse the data. RESULTS: The
      analysis was based on 404 nurses (45% of the full-time working population of
      nurses). The highest mean scores recorded for the positive work-related
      psychosocial factors studied were meaning of work, role clarity, social
      relationships and mutual trust between employees. The highest scores for the
      negative factors studied were the demands for hiding emotions, work pace,
      cognitive and emotional demands. Stress and burnout showed the highest mean
      scores amongst the MHPs. Quantitative and emotional demands were positively
      related to all of the studied MHPs, while work pace and role conflicts had a
      positive correlation with stress and burnout. All of the studied negative
      psychosocial factors were significantly correlated with burnout. CONCLUSIONS:
      work-related psychosocial risk factors such as quantitative demands work load,
      emotional demands, work pace and role conflicts, had significant positive
      relationships with MHPS in nurses in Estonia, and may contribute to high levels
      of stress as well as burnout amongst nurses: .

PMID- 25851018
TI  - Efficacy of dexmedetomidine on postoperative shivering: a meta-analysis of
      clinical trials.
AB  - PURPOSE: Shivering is a frequent complication in the postoperative period. The
      aim of the current meta-analysis was to assess the efficacy of dexmedetomidine on
      postoperative shivering. METHODS: Two researchers independently searched PubMed,
      EMBASE and the Cochrane Central Register of Controlled Trials for controlled
      clinical trials. The meta-analysis was performed by Review Manager. RESULTS:
      Thirty-nine trials with 2,478 patients were included in this meta-analysis.
      Dexmedetomidine reduced postoperative shivering compared with placebo (risk ratio
      [RR] = 0.26; 95% confidence interval [CI]: 0.20 to 0.34), with a minimum
      effective dose of 0.5 ug.kg(-1) (RR = 0.36; 95% CI: 0.21 to 0.60). The anti
      shivering effect can be achieved both intravenously and epidurally when
      administered within two hours prior to the end of surgery. The efficacy of
      dexmedetomidine was similar to widely used anti-shivering agents, such as
      fentanyl, meperidine, tramadol, clonidine and so on; however, dexmedetomidine may
      increase the incidence of sedation, hypotension, bradycardia and dry mouth.
      CONCLUSIONS: The present meta-analysis indicates that dexmedetomidine shows
      superiority over placebo, but not over other anti-shivering agents. Therefore,
      considering its high price and potential adverse events, dexmedetomidine may not
      be appropriate solely for the purpose of the prevention of postoperative
      shivering.

PMID- 25851019
TI  - Extracorporeal membrane oxygenation for blastomycosis-related acute respiratory
      distress syndrome: a case series.
AB  - PURPOSE: Blastomyces dermatitidis is a dimorphic fungus endemic to North America
      capable of causing fatal respiratory failure. Acute respiratory distress syndrome
      (ARDS) complicates up to 10% of pulmonary blastomycosis in hospitalized patients
      and carries a mortality of 50-90%. This report describes the clinical course of
      four consecutive patients with blastomycosis-related ARDS treated with venovenous
      extracorporeal membrane oxygenation (ECMO) during 2009-2014. CLINICAL FEATURES:
      Four adults were referred from northwestern Ontario, Canada with progressive
      respiratory illnesses. All patients developed diffuse bilateral opacities on
      chest radiography and required mechanical ventilation within 6-72 hr. Patients
      satisfied Berlin criteria for severe ARDS with trough PaO2/F i O2 ratios of 44-61
      on positive end-expiratory pressure of 12-24 cm H2O. Wet mount microscopy from
      respiratory samples showed broad-based yeast consistent with B.dermatitidis.
      Despite lung protective ventilation strategies with maximal F i O2 (patients A
      D), neuromuscular blockade (patients A-D), inhaled nitric oxide (patients A and
      D), and prone positioning (patient D), progressive hypoxemia resulted in
      initiation of venovenous ECMO by hours 24-90 of mechanical ventilation with
      subsequent de-escalation of ventilatory support. In all four cases, ECMO
      decannulation was performed (7-23 days), mechanical ventilation was withdrawn (18
      52 days), and the patients survived to hospital discharge (31-87 days).
      CONCLUSION: This report describes the successful application of ECMO as rescue
      therapy in aid of four patients with refractory blastomycosis-associated ARDS. In
      addition to early appropriate antimicrobial therapy, transfer to an institution
      experienced with ECMO should be considered when caring for patients from endemic
      areas with rapidly progressive respiratory failure.

PMID- 25851020
TI  - Combined saphenous and sciatic catheters for analgesia after major ankle surgery:
      a double-blinded randomized controlled trial.
AB  - PURPOSE: Continuous sciatic nerve block is used for pain management following
      major ankle surgery. Pain from the saphenous nerve territory often persists. We
      conducted a double-blinded randomized placebo-controlled trial to evaluate the
      effect of a supplementary saphenous catheter in the proximal thigh combined with
      a popliteal sciatic catheter and single-shot saphenous nerve block after major
      ankle surgery. METHODS: Fifty patients received both sciatic and saphenous
      continuous catheters inserted along the short axis of the nerves with ultrasound
      guidance. All patients had an initial sciatic nerve block followed by a
      continuous sciatic catheter infusion and an initial saphenous nerve block with
      ropivacaine. Participants were then randomized to infusion of either ropivacaine
      or isotonic saline in the saphenous catheter for 48 hr postoperatively. The
      primary outcome was total intravenous morphine consumption during the first 48 hr
      postoperatively. Secondary outcomes were clinical analgesia, saphenous analgesia,
      territory of worst pain, and patient satisfaction. RESULTS: Forty-four patients
      were included in the analysis. The mean (SD) 48-hr morphine consumption was 24.7
      (21.6) mg in the intervention group and 27.8 (20.1) mg in the placebo group (P =
      0.63). The mean difference in 48-hr morphine consumption was 3.0 mg (95%
      confidence interval, -9.7 to 15.7). There were no differences regarding the
      secondary outcomes. CONCLUSION: A saphenous catheter with a low-dose continuous
      infusion of ropivacaine, as an adjunct to a sciatic catheter, had no effect on
      the postoperative analgesia after major ankle surgery when both catheters were
      inserted along the short axis of the nerves. This trial was registered at
      ClinicalTrials.gov (NCT01445210).

PMID- 25851024
TI  - Bony nasolacrimal duct dehiscence in functional endoscopic sinus surgery:
      radiological study and discussion of surgical implications.
AB  - OBJECTIVES: To analyse the radiological features of the bony nasolacrimal duct
      before and after functional endoscopic sinus surgery, and document the incidence
      of surgically induced dehiscence. METHODS: A retrospective case series analysis
      was conducted of 63 consecutive patients who underwent uncinectomy as a part of
      118 functional endoscopic sinus surgical procedures. All patients underwent pre-
      and post-operative computed tomography scans. Axial computed tomography images at
      the level of maxillary sinus were evaluated for the presence of bony nasolacrimal
      duct dehiscence, osteitis and completeness of uncinectomy. RESULTS: The rate of
      nasolacrimal duct dehiscence prior to surgery was 6.8 per cent (8 out of 118
      cases). Nasolacrimal duct dehiscence as a consequence of surgery was observed in
      3.3 per cent of cases (4 out of 118), with a further 4.2 per cent (5 out of 118)
      showing post-operative reactive bony change of the nasolacrimal duct in the
      absence of dehiscence. CONCLUSION: The incidence of nasolacrimal duct injury
      observed was much lower than that previously reported in the literature.

PMID- 25851023
TI  - Interplay between chemotaxis and contact inhibition of locomotion determines
      exploratory cell migration.
AB  - Directed cell migration in native environments is influenced by multiple
      migratory cues. These cues may include simultaneously occurring attractive
      soluble growth factor gradients and repulsive effects arising from cell-cell
      contact, termed contact inhibition of locomotion (CIL). How single cells
      reconcile potentially conflicting cues remains poorly understood. Here we show
      that a dynamic crosstalk between epidermal growth factor (EGF)-mediated
      chemotaxis and CIL guides metastatic breast cancer cell motility, whereby cells
      become progressively insensitive to CIL in a chemotactic input-dependent manner.
      This balance is determined via integration of protrusion-enhancing signalling
      from EGF gradients and protrusion-suppressing signalling induced by CIL, mediated
      in part through EphB. Our results further suggest that EphB and EGF signalling
      inputs control protrusion formation by converging onto regulation of
      phosphatidylinositol 3-kinase (PI3K). We propose that this intricate interplay
      may enhance the spread of loose cell ensembles in pathophysiological conditions
      such as cancer, and possibly other physiological settings. 

PMID- 25851025
TI  - A Randomized Double Blind Clinical Trial on a Sabgh Formulation for Patients With
      Vitiligo.
AB  - BACKGROUND: The cosmetic problem that vitiligo produces affects patients
      psychologically. Many patients with vitiligo are suggested to cover their white
      skin patches with cosmetic products. There are formulations in traditional
      Iranian pharmacy to color these white skin patches. In this study, one of these
      formulations was compared with a cosmetic formulation. METHODS: Two groups of
      patients were selected. One group used a marketed formulation and other group
      used a traditional Iranian Pharmacy formulation. The quality of life of the
      patients was compared based on the Dermatology Life Quality Index Questionnaire.
      RESULTS: Both interventions were associated with statistically improved
      Dermatology Life Quality Index scores over the 8-week intervention (P < .05),
      although the difference between the 2 was not statistically significant (P =
      .436). CONCLUSION: Traditional Iranian Pharmacy formulation is effective in
      increasing the quality of life in vitiligo patients.

PMID- 25851026
TI  - Combined hydrophobicity and mechanical durability through surface
      nanoengineering.
AB  - This paper reports combined hydrophobicity and mechanical durability through the
      nanoscale engineering of surfaces in the form of nanorod-polymer composites.
      Specifically, the hydrophobicity derives from nanoscale features of mechanically
      hard ZnO nanorods and the mechanical durability derives from the composite
      structure of a hard ZnO nanorod core and soft polymer shell. Experimental
      characterization correlates the morphology of the nanoengineered surfaces with
      the combined hydrophobicity and mechanical durability, and reveals the
      responsible mechanisms. Such surfaces may find use in applications, such as boat
      hulls, that benefit from hydrophobicity and require mechanical durability. 

PMID- 25851027
TI  - Candidemia Diagnosed from Peripheral Blood Smear: Case Report and Review of
      Literature 1954-2013.
AB  - BACKGROUND: Yeast with pseudohyphae or those that have been phagocytized by white
      blood cells are coincidentally found in peripheral blood smears. The clinical
      diagnostic value and outcome of candidaemia diagnosed from peripheral blood
      smears (CPBSs) are unclear. CASE PRESENTATION: A 45-year-old man with diabetes
      and panhypopituitarism for 20 years received 10 mg of hydrocortisone and 100 MUg
      of levothyroxine sodium hydrate daily. He has been admitted seven times because
      of adrenal failure triggered by infections and was admitted for pneumonia. On day
      56, some budding yeast was found microscopically in a peripheral blood smear with
      May-Giemsa staining. Some of them were phagocytized by white blood cells. The two
      blood cultures yielded Candida parapsilosis. Despite antifungal treatment and
      removal of an intravenous catheter, on day 98 (42 days after the candidaemia
      diagnosis), the patient died. CONCLUSION: We analysed 36 cases including the
      present case. Almost all CPBS patients (96.5 %, n = 29) were using an intravenous
      catheter. The most frequently isolated species was C. parapsilosis (35.1 %),
      followed by C. albicans (29.7 %). The overall mortality rate was 53.6 % (n = 28).
      The time from the discovery of yeast-like pathogens using peripheral blood smears
      to death ranged from a few hours to 93 days (median 19 days). The present results
      suggest that intravenous catheter use and the underlying conditions of patients
      are responsible for CPBSs. The detection of yeast in peripheral blood smears
      suggests advanced infections with uncontrollable complications, which means a
      poor prognosis. Rapid detection methods besides blood culture are needed.

PMID- 25851029
TI  - Arm Orthosis/Prosthesis Movement Control Based on Surface EMG Signal Extraction.
AB  - This paper shows experimental results on electromyography (EMG)-based system
      control applied to motorized orthoses. Biceps and triceps EMG signals are
      captured through two biometrical sensors, which are then filtered and processed
      by an acquisition system. Finally an output/control signal is produced and sent
      to the actuators, which will then perform the actual movement, using algorithms
      based on autoregressive (AR) models and neural networks, among others. The
      research goal is to predict the desired movement of the lower arm through the
      analysis of EMG signals, so that the movement can be reproduced by an arm
      orthosis, powered by two linear actuators. In this experiment, best accuracy has
      achieved values up to 91%, using a fourth-order AR-model and 100ms block length. 

PMID- 25851028
TI  - Differentiation of focal nodular hyperplasia from hepatocellular adenoma: Role of
      the quantitative analysis of gadobenate dimeglumine-enhanced hepatobiliary phase
      MRI.
AB  - PURPOSE: To determine the value of quantitative analysis of the hepatobiliary
      phase (HBP) in gadobenate dimeglumine (Gd-BOPTA)-enhanced magnetic resonance
      imaging (MRI) to differentiate focal nodular hyperplasia (FNH) from
      hepatocellular adenoma (HCA). MATERIALS AND METHODS: Thirty-eight patients
      bearing 67 lesions (40 FNH; 27 HCA) were retrospectively included in this
      Institutional Review Board-approved study. The same volumetric interpolated
      breath-hold examination (VIBE) T1 -weighted sequences were performed before and
      after contrast injection on a 1.5T MRI, with HBP images acquired with a mean
      delay of 80 minutes (range 60-120 min). After a visual assessment of lesions
      enhancement (qualitative HBP analysis), the HBP signal intensity ratio (SIR) and
      the lesion-to-liver contrast enhancement ratio (LLCER) were calculated for each
      lesion by two observers (Mann-Whitney test). The sensitivities, specificities
      (receiver operating characteristic [ROC] curve analysis) and interobserver
      correlation (intraclass coefficient, ICC) of quantitative HBP analysis were
      determined. RESULTS: All FNH and 44.4% of HCA appeared hyper- or isointense
      relative to the adjacent liver on qualitative HBP analysis. The mean SIR (P <
      0.01) and LLCER (P < 0.0001) of FNH were significantly higher than that of HCA.
      The area under the ROC curve for the differentiation of FNH from HCA with LLCER
      was 0.98 for both observers. With a cutoff value of -0.3%-observer 1 with highest
      experience- LLCER assessment provided respective sensitivity and specificity
      values of 100% and 96.2% for the differentiation of FNH from HCA. The ICC was 0.7
      for SIR measurements and 0.8 for LLCER measurements. CONCLUSION: Quantitative
      LLCER assessment allows an accurate differentiation of FNH from HCA, even in
      hyper- or isointense HCA on HBP images.

PMID- 25851030
TI  - Growth rate hypothesis and efficiency of protein synthesis under different
      sulphate concentrations in two green algae.
AB  - The growth rate hypothesis (GRH) predicts a positive correlation between growth
      rate and RNA content because growth depends upon the protein synthesis machinery.
      The application of this hypothesis to photoautotrophic organisms has been
      questioned. We tested the GRH on one prasinophycean, Tetraselmis suecica, and one
      chlorophycean, Dunaliella salina, grown at three sulphate concentrations.
      Sulphate was chosen because its concentration in the oceans increased through
      geological time and apparently had a role in the evolutionary trajectories of
      phytoplankton. Cell protein content and P quota were positively related to the
      RNA content (r = 0.62 and r = 0.74, respectively). The correlation of the RNA
      content with growth rates (r = 0.95) indicates that the GRH was valid for these
      species when growth rates were below 0.82 d(-1) . 

PMID- 25851031
TI  - Patients' willingness to utilize a SMS-based appointment scheduling system at a
      family practice unit in a developing country.
AB  - Aim The investigators aimed to assess the willingness of patients to utilize and
      pay for a proposed short message service- (SMS) based appointment scheduling
      service. BACKGROUND: Telecommunication applications have been introduced to
      improve the delivery of healthcare services in developed countries; however,
      public-funded healthcare systems in developing countries like Nigeria are mostly
      unfamiliar with the use of such technologies for improving healthcare access.
      METHODS: We proposed a SMS-based (text message) appointment scheduling system to
      consenting subjects at an outpatients' clinic and explored their willingness to
      utilize and pay for the service. Using semi-structured interview schedules, we
      collected information on: estimated arrival time, most important worry when
      seeking for healthcare services at public hospitals in the study setting,
      ownership of a mobile phone, willingness to utilize a SMS-based appointment for
      clinic visits and willingness to pay for the service. In addition, respondents
      were asked to suggest a tariff for the proposed system. Findings A total of 500
      consecutively recruited patients aged 16-86 (42.1+/-15.4) years participated; 54%
      (n=270) were females. Waiting time ranged from 1-7.5 h (3.9+/-1.1). Two
      overlapping themes emerged as most important worries: crowded waiting rooms and
      long waiting time. Ownership of mobile phones was reported by 96.4% (n=482) of
      subjects. Nearly all favoured the proposed appointment scheduling system (n=486,
      97.2%). Majority of patients who favoured the system were willing to pay for the
      service (n=484, 99.6%). Suggested tariff ranged from 0.03 to 20.83 (1.53+/-2.11)
      US dollars; 89.8% (n=349) of the subjects suggested tariffs that were greater
      than the prevailing retail cost of the proposed service. In sum, our findings
      indicate that patients in this study were willing to utilize and pay for a
      proposed SMS-based appointment scheduling system. The findings have implications
      for policies aimed at improving healthcare access and delivery of healthcare
      services at the primary care level in developing countries like Nigeria.

PMID- 25851032
TI  - Solubility prediction, solvate and cocrystal screening as tools for rational
      crystal engineering.
AB  - OBJECTIVES: The fact that novel drug candidates are becoming increasingly
      insoluble is a major problem of current drug development. Computational tools may
      address this issue by screening for suitable solvents or by identifying potential
      novel cocrystal formers that increase bioavailability. In contrast to other more
      specialized methods, the fluid phase thermodynamics approach COSMO-RS (conductor
      like screening model for real solvents) allows for a comprehensive treatment of
      drug solubility, solvate and cocrystal formation and many other thermodynamics
      properties in liquids. This article gives an overview of recent COSMO-RS
      developments that are of interest for drug development and contains several new
      application examples for solubility prediction and solvate/cocrystal screening.
      METHODS: For all property predictions COSMO-RS has been used. The basic concept
      of COSMO-RS consists of using the screening charge density as computed from first
      principles calculations in combination with fast statistical thermodynamics to
      compute the chemical potential of a compound in solution. KEY FINDING: The fast
      and accurate assessment of drug solubility and the identification of suitable
      solvents, solvate or cocrystal formers is nowadays possible and may be used to
      complement modern drug development. Efficiency is increased by avoiding costly
      quantum-chemical computations using a database of previously computed molecular
      fragments. SUMMARY: COSMO-RS theory can be applied to a range of physico-chemical
      properties, which are of interest in rational crystal engineering. Most notably,
      in combination with experimental reference data, accurate quantitative solubility
      predictions in any solvent or solvent mixture are possible. Additionally, COSMO
      RS can be extended to the prediction of cocrystal formation, which results in
      considerable predictive accuracy concerning coformer screening. In a recent
      variant costly quantum chemical calculations are avoided resulting in a
      significant speed-up and ease-of-use.

PMID- 25851033
TI  - A cAMP Biosensor-Based High-Throughput Screening Assay for Identification of Gs
      Coupled GPCR Ligands and Phosphodiesterase Inhibitors.
AB  - Cyclic adenosine 3',5'-monophosphate (cAMP) is an important second messenger, and
      quantification of intracellular cAMP levels is essential in studies of G protein
      coupled receptors (GPCRs). The intracellular cAMP levels are regulated by the
      adenylate cyclase (AC) upon activation of either Gs- or Gi-coupled GPCRs, which
      leads to increased or decreased cAMP levels, respectively. Here we describe a
      real-time Forster resonance energy transfer (FRET)-based cAMP high-throughput
      screening (HTS) assay for identification and characterization of Gs-coupled GPCR
      ligands and phosphodiesterase (PDE) inhibitors in living cells. We used the beta2
      adrenergic receptor (beta(2)AR) as a representative Gs-coupled receptor and
      characterized two cell lines with different expression levels. Low receptor
      expression allowed detection of desensitization kinetics and delineation of
      partial agonism, whereas high receptor expression resulted in prolonged signaling
      and enabled detection of weak partial agonists and/or ligands with low potency,
      which is highly advantageous in large HTS settings and hit identification. In
      addition, the assay enabled detection of beta(2)AR inverse agonists and PDE
      inhibitors. High signal-to-noise ratios were also observed for the other
      representative Gs-coupled GPCRs tested, GLP-1R and GlucagonR. The FRET-based cAMP
      biosensor assay is robust, reproducible, and inexpensive with good Z factors and
      is highly applicable for HTS.

PMID- 25851035
TI  - Development of an HTS-Compatible Assay for the Discovery of Ulk1 Inhibitors.
AB  - A rapidly accumulating body of work suggests the autophagy pathway is an
      attractive therapeutic target for neurodegenerative diseases and cancer. To
      validate autophagy as an anticancer strategy and to assess if systemic inhibition
      of the pathway will have deleterious effects on normal tissues and physiology,
      highly selective autophagy inhibitors are needed. While several inducers and
      inhibitors of autophagy are known, all are nonspecific and none target the
      enzymes that execute the pathway. A central upstream regulator of the autophagy
      pathway is the serine/threonine kinase Ulk1 (UNC-51-like kinase-1). Selective
      molecular probes that function as Ulk1-specific inhibitors are needed to improve
      our understanding of the autophagy pathway. To identify inhibitors of Ulk1 kinase
      activity, we developed an HTS-compatible, homogeneous biochemical assay using
      AlphaScreen technology. This novel assay design uses purified stress-activated
      Ulk1 and monitors phosphorylation of its full-length native substrate, Atg13.
      This assay was optimized and validated in a 384-well format by screening the
      Sigma LOPAC library. Here we report that the Ulk1 AlphaScreen assay is robust and
      reproducible, with a Z' factor value of 0.83 +/- 0.02 and a signal to background
      ratio of 20 +/- 1.2. Thus, this assay can be used to screen large chemical
      libraries to discover novel inhibitors of Ulk1. 

PMID- 25851034
TI  - Electroporation Knows No Boundaries: The Use of Electrostimulation for siRNA
      Delivery in Cells and Tissues.
AB  - The discovery of RNA interference (RNAi) has enabled several breakthrough
      discoveries in the area of functional genomics. The RNAi technology has emerged
      as one of the major tools for drug target identification and has been steadily
      improved to allow gene manipulation in cell lines, tissues, and whole organisms.
      One of the major hurdles for the use of RNAi in high-throughput screening has
      been delivery to cells and tissues. Some cell types are refractory to high
      efficiency transfection with standard methods such as lipofection or calcium
      phosphate precipitation and require different means. Electroporation is a
      powerful and versatile method for delivery of RNA, DNA, peptides, and small
      molecules into cell lines and primary cells, as well as whole tissues and
      organisms. Of particular interest is the use of electroporation for delivery of
      small interfering RNA oligonucleotides and clustered regularly interspaced short
      palindromic repeats/Cas9 plasmid vectors in high-throughput screening and for
      therapeutic applications. Here, we will review the use of electroporation in high
      throughput screening in cell lines and tissues. 

PMID- 25851036
TI  - A Screening Assay Cascade to Identify and Characterize Novel Selective Estrogen
      Receptor Downregulators (SERDs).
AB  - Here, we describe an approach to identify novel selective estrogen receptor
      downregulator (SERD) compounds with improved properties such as oral
      bioavailability and the potential of increased efficacy compared to currently
      marketed drug treatments. Previously, methodologies such as Western blotting and
      transient cell reporter assays have been used to identify and characterize SERD
      compounds, but such approaches can be limited due to low throughput and
      sensitivity, respectively. We have used an endogenous cell-imaging strategy that
      has both the throughput and sensitivity to support a large-scale hit-to-lead
      program to identify novel compounds. A screening cascade with a suite of assays
      has been developed to characterize compounds that modulate estrogen receptor
      alpha (ERalpha)-mediated signaling or downregulate ERalpha levels in cells.
      Initially, from a focused high-throughput screening, novel ERalpha binders were
      identified that could be modified chemically into ERalpha downregulators.
      Following this, cellular assays helped determine the mechanism of action of
      compounds to distinguish between on-target and off-target compounds and
      differentiate SERDs, selective estrogen receptor modulator (SERM) compounds, and
      agonist ERalpha ligands. Data are shown to exemplify the characterization of
      ERalpha-mediated signaling inhibitors using a selection of literature compounds
      and illustrate how this cascade has been used to drive the chemical design of
      novel SERD compounds. 

PMID- 25851038
TI  - Pulsed microdischarge with inductively coupled plasma mass spectrometry for
      elemental analysis on solid metal samples.
AB  - Pulsed microdischarge employed as source for direct solid analysis was
      investigated in N2 environment at atmospheric pressure. Compared with direct
      current (DC) microdischarge, it exhibits advantages with respect to the ablation
      and emission of the sample. Comprehensive evidence, including voltage-current
      relationship, current density (j), and electron density (ne), suggests that
      pulsed microdischarge is in the arc regime while DC microdischarge belongs to
      glow. Capability in ablating metal samples demonstrates that pulsed
      microdischarge is a viable option for direct solid sampling because of the
      enhanced instantaneous energy. Using optical spectrometer, only common emission
      lines of N2 can be acquired in DC mode, whereas primary atomic and ionic lines of
      the sample are obtained in the case of pulsed mode. Calculations show a
      significant difference in N2 vibrational temperatures between DC and pulsed
      microdischarge. Combined with inductively coupled plasma mass spectrometry
      (ICPMS), pulsed microdischarge exhibits much better performances in calibration
      linearity and limits of detection (LOD) than those of DC discharge in direct
      analysis of samples of different matrices. To improve transmission efficiency, a
      mixture of Ar and N2 was employed as discharge gas as well as carrier gas in
      follow-up experiments, facilitating that LODs of most elements reached ng/g. 

PMID- 25851037
TI  - A Quantitative Microtiter Assay for Sialylated Glycoform Analyses Using Lectin
      Complexes.
AB  - Fidelity of glycan structures is a key requirement for biotherapeutics, with
      carbohydrates playing an important role for therapeutic efficacy. Comprehensive
      glycan profiling techniques such as liquid chromatography (LC) and mass
      spectrometry (MS), while providing detailed description of glycan structures,
      require glycan cleavage, labeling, and paradigms to deconvolute the considerable
      data sets they generate. On the other hand, lectins as probes on microarrays have
      recently been used in orthogonal approaches for in situ glycoprofiling but
      require analyte labeling to take advantage of the capabilities of automated
      microarray readers and data analysis they afford. Herein, we describe a lectin
      based microtiter assay (lectin-enzyme-linked immunosorbent assay [ELISA]) to
      quantify terminal glycan moieties, applicable to in vitro and in-cell glycan
      engineered Fc proteins as well as intact IgGs from intravenous immunoglobulin
      (IVIG), a blood product containing pooled polyvalent IgG antibodies extracted
      from plasma from healthy human donors. We corroborate our findings with industry
      standard LC-MS profiling. This "customizable" ELISA juxtaposes readouts from
      multiple lectins, focusing on a subset of glycoforms, and provides the ability to
      discern single- versus dual-arm glycosylation while defining levels of epitopes
      at sensitivities comparable to MS. Extendable to other biologics, this ELISA can
      be used stand-alone or complementary to MS for quantitative glycan analysis. 

PMID- 25851039
TI  - Cytotoxicity evaluation of polymer-derived ceramics for pacemaker electrode
      applications.
AB  - Ceramics are known to be chemically stable, and the possibility to electrically
      dope polymer-derived ceramics makes it a material of interest for implantable
      electrode applications. We investigated cytotoxic characteristics of four polymer
      derived ceramic candidates with either electrically conductive or insulating
      properties. Cytotoxicity was assessed by culturing C2C12 myoblast cells under two
      conditions: by exposing them to material extracts and by putting them directly in
      contact with material samples. Cell spreading was optically evaluated by
      comparing microscope observations immediately after the materials insertion and
      after 24 h culturing. Cell viability (MTT) and mortality (LDH) were quantified
      after 24-h incubation in contact with the materials. Comparison was made with
      biocompatible positive references (alumina, platinum, biocompatible stainless
      steel 1.4435), negative references (latex, stainless steel 1.4301) and controls
      (no material present in the culture wells). We found that the cytotoxic
      properties of tested ceramics are comparable to established reference materials.
      These ceramics, which are reported to be very stable, can be microstructured and
      electrically doped to a wide range of conductivity and are thus excellent
      candidates for implantable electrode applications including pacemakers.

PMID- 25851040
TI  - Combined accurate platelet enumeration and reticulated platelet determination by
      flow cytometry.
AB  - BACKGROUND: Diagnosing the cause of thrombocytopenia often requires a bone marrow
      aspiration or biopsy, an invasive procedure. Reticulated platelets (RP) are
      immature RNA containing platelets, accurate RP enumeration has yet to be
      achieved, partially due to the lack of a robust reference method. GOAL: To refine
      previous work and gating strategies distinguishing RP from mature platelets while
      incorporating accurate platelet enumeration into the analysis. After reviewing
      previously published studies on Thiazole Orange (TO) staining of RP, we
      systematically evaluated CD41/CD61 in combination with a commercial source of TO
      (BDBiosciences). Previous RP methods have not taken advantage of platelet
      enumeration therefore our goal was to incorporate the ICSH platelet enumeration
      protocol into our method. METHODS: TO concentration, incubation, and fixation
      method were determined to be 10% of stock concentration, 30 min, and 1%
      formaldehyde respectively. Gating strategy to determine RP fraction used an
      unstained control tube to set the limit of TO staining. RESULTS: Normal range (n
      = 51) was 9.9 +/- 3.1%. Analysis of 40 patients with immune-thrombocytopenia
      purpura (ITP) showed a RP range from 4.3% to 81.2%. Platelet enumeration was
      consistent with our previous studies in this area. CONCLUSIONS: Combining
      CD41/CD61 platelet enumeration with TO RP percentage is possible. Accurate RP
      percentage requires an effective gating strategy, as background fluorescence
      cursor placement is important. This method for enumeration of RP percentage
      combined with accurate platelet enumeration, particularly in the low range,
      should prove useful in differentiating production from consumption issues in
      thrombocytopenia and monitoring response to therapy.

PMID- 25851041
TI  - Biotin[6]uril Esters: Chloride-Selective Transmembrane Anion Carriers Employing C
      H...Anion Interactions.
AB  - Biotin[6]uril hexaesters represent a new class of anionophores which operate
      solely through C-H...anion interactions. The use of soft H-bond donors favors the
      transport of less hydrophilic anions (e.g., Cl(-), NO3(-)) over hard, stongly
      hydrated anions (e.g., HCO3(-) and SO4(2-)). Especially relevant is the
      selectivity between chloride and bicarbonate, the major inorganic anions in
      biological systems. 

PMID- 25851046
TI  - Misclassification of iodine intake level from morning spot urine samples with
      high iodine excretion among Inuit and non-Inuit in Greenland.
AB  - Iodine nutrition is commonly assessed from iodine excretion in urine. A 24 h
      urine sample is ideal, but it is cumbersome and inconvenient. Hence, spot urine
      samples with creatinine to adjust for differences in void volume are widely used.
      Still, the importance of ethnicity and the timing of spot urine samples need to
      be settled. We, thus, collected 104 early morning spot urine samples and 24 h
      urine samples from Inuit and non-Inuit living in Greenland. Diet was assessed by
      a FFQ. Demographic data were collected from the national registry and by
      questionnaires. Iodine was measured using the Sandell-Kolthoff reaction,
      creatinine using the Jaffe method and para-amino benzoic acid by the HPLC method
      for the estimation of completeness of urine sampling and compensation of
      incomplete urine samples to 24 h excretion. A population-based recruitment was
      done from the capital city, a major town and a settlement (n 36/48/20).
      Participants were seventy-eight Inuit and twenty-six non-Inuit. The median 24 h
      iodine excretion was 138 (25th-75th percentile 89-225) MUg/97 (25th-75th
      percentile 72-124) MUg in Inuit/non-Inuit (P= 0.030), and 153 (25th-75th
      percentile 97-251) MUg/102 (25th-75th percentile 73-138) MUg (P= 0.026) when
      including compensated iodine excretion. Iodine excretion in 24 h urine samples
      increased with a rising intake of traditional Inuit foods (P= 0.005). Iodine
      excretion was lower in morning spot urine samples than in 24 h urine samples (P<
      0.001). This difference was associated with iodine intake levels (P< 0.001), and
      was statistically significant when the iodine excretion level was above 150
      MUg/24 h. In conclusion, the iodine intake level was underestimated from morning
      spot urine samples if iodine excretion was above the recommended level.

PMID- 25851047
TI  - Concise Review: Prospects of Bone Marrow Mononuclear Cells and Mesenchymal Stem
      Cells for Treating Status Epilepticus and Chronic Epilepsy.
AB  - Mononuclear cells (MNCs) and mesenchymal stem cells (MSCs) derived from the bone
      marrow and other sources have received significant attention as donor cells for
      treating various neurological disorders due to their robust neuroprotective and
      anti-inflammatory effects. Moreover, it is relatively easy to procure these cells
      from both autogenic and allogenic sources. Currently, there is considerable
      interest in examining the usefulness of these cells for conditions such as status
      epilepticus (SE) and chronic epilepsy. A prolonged seizure activity in SE
      triggers neurodegeneration in the limbic brain areas, which elicits
      epileptogenesis and evolves into a chronic epileptic state. Because of their
      potential for providing neuroprotection, diminishing inflammation and curbing
      epileptogenesis, early intervention with MNCs or MSCs appears attractive for
      treating SE as such effects may restrain the development of chronic epilepsy
      typified by spontaneous seizures and learning and memory impairments. Delayed
      administration of these cells after SE may also be useful for easing spontaneous
      seizures and cognitive dysfunction in chronic epilepsy. This concise review
      evaluates the current knowledge and outlook pertaining to MNC and MSC therapies
      for SE and chronic epilepsy. In the first section, the behavior of these cells in
      animal models of SE and their efficacy to restrain neurodegeneration,
      inflammation, and epileptogenesis are discussed. The competence of these cells
      for suppressing seizures and improving cognitive function in chronic epilepsy are
      conferred in the next section. The final segment ponders issues that need to be
      addressed to pave the way for clinical application of these cells for SE and
      chronic epilepsy.

PMID- 25851048
TI  - Duchenne muscular dystrophy diagnostics: it only gets better but some of the same
      challenges remain.

PMID- 25851049
TI  - Estimating Protistan Diversity Using High-Throughput Sequencing.
AB  - Sequencing hypervariable regions from the 18S rRNA gene is commonly employed to
      characterize protistan biodiversity, yet there are concerns that short reads do
      not provide the same taxonomic resolution as full-length sequences. A total of
      7,432 full-length sequences were used to perform an in silico analysis of how
      sequences of various lengths and target regions impact downstream ecological
      interpretations. Sequences that were longer than 400 nucleotides and included the
      V4 hypervariable region generated results similar to those derived from full
      length 18S rRNA gene sequences. Present high-throughput sequencing capabilities
      are approaching protistan diversity estimation comparable to whole gene
      sequences. 

PMID- 25851050
TI  - 2015 SCAI/ACC/HFSA/STS Clinical Expert Consensus Statement on the Use of
      Percutaneous Mechanical Circulatory Support Devices in Cardiovascular Care
      (Endorsed by the American Heart Association, the Cardiological Society of India,
      and Sociedad Latino Americana de Cardiologia Intervencion; Affirmation of Value
      by the Canadian Association of Interventional Cardiology-Association Canadienne
      de Cardiologie D'intervention).
AB  - Although historically the intra-aortic balloon pump has been the only mechanical
      circulatory support device available to clinicians, a number of new devices have
      become commercially available and have entered clinical practice. These include
      axial flow pumps, such as Impella(r); left atrial to femoral artery bypass pumps,
      specifically the TandemHeart; and new devices for institution of extracorporeal
      membrane oxygenation. These devices differ significantly in their hemodynamic
      effects, insertion, monitoring, and clinical applicability. This document reviews
      the physiologic impact on the circulation of these devices and their use in
      specific clinical situations. These situations include patients undergoing high
      risk percutaneous coronary intervention, those presenting with cardiogenic shock,
      and acute decompensated heart failure. Specialized uses for right-sided support
      and in pediatric populations are discussed and the clinical utility of mechanical
      circulatory support devices is reviewed, as are the American College of
      Cardiology/American Heart Association clinical practice guidelines.

PMID- 25851051
TI  - Optimization and automation of an end-to-end high throughput microscale transient
      protein production process.
AB  - High throughput protein production from transient transfection of mammalian cells
      is used in multiple facets of research and development studies. Commonly used
      formats for these high number expressions are 12-, 24- and 96-well plates at
      various volumes. However there are no published examples of a 96-deep well plate
      microscale (1,000 MUL) suspension process for mammalian transient expression. For
      this reason, we aimed to determine the optimal operating conditions for a high
      producing, microscale HEK293 transient system. We evaluated the hydrodynamic flow
      and measured the oxygen transfer rate (OTR) and transient protein expression for
      96-deep well plates of different well geometries filled at 600-1,000 MUL working
      volumes and agitated at various speeds and orbital diameters. Ultimately, a round
      well-round bottom (RR) 96-deep well plate with a working volume of 1,000 uL
      agitated at 1,000 RPM and a 3 mm orbital diameter yielded the highest and most
      consistent total transient protein production. As plate cultures are subject to
      evaporation, water loss from different plate seals was measured to identify an
      optimal plate sealing method. Finally, to enable higher capacity protein
      production, both expression and purification processes were automated.
      Functionality of this end-to-end automation workflow was demonstrated with the
      generation of high levels of human IgG1 antibodies (>=360 ug/mL) with
      reproducible productivity, product quality and >=78% purification recovery.

PMID- 25851053
TI  - [Endoscopy of the Lacrimal Duct System in Children].
AB  - BACKGROUND: Pathologies of the lacrimal duct system show a frequent occurrence in
      paediatric ophthalmology. Mostly, the connection between the nasolacrimal duct
      and the nose fails to open but also combined diseases or congenital anomalies may
      be the reason. Because of complications, the chance for healing after a
      conservative therapeutic approach decreases and surgical intervention is
      necessary. PATIENTS AND METHODS: The opportunity for transcanalicular endoscopy
      of the lacrimal duct system in children is shown by the presentation of three
      different case reports. Typical clinical findings are given and the use of
      dacryoendoscopy for diagnostic and therapeutic benefit is pointed out. Therefore,
      we present an 8-week-old child, suffering recurrent purulent inflammation due to
      an amniotocele (1), a 5-year-old child having a congenital lacrimal fistula (2)
      and another 5-year-old child with a severe chronic dacryocystitis of both eyes
      after several lacrimal duct surgeries showing remaining intrasaccal silicone
      tubes (3). RESULTS: In all these cases transcanalicular endoscopy could be used
      successfully for reconstruction of the lacrimal duct systems. A bullous Hasner's
      membrane could be localized and opened (1). The lacrimal fistula was identified
      to communicate with the common canaliculus and combined stenosis of the
      canaliculus and saccus were treated (2). In the third case fragments of
      intrasaccal silicone tubes could be localised and the foreign bodies could be
      evacuated by transcanalicular surgery (3). The children with lacrimal fistula and
      the intrasaccal foreign bodies were treated with self-threading silicone tubing
      which was removed three months later. In the follow-up period (16 months in case
      2, 22 months in case 3 and 38 months in case 1) recurrences of the lacrimal
      pathologies or clinical complaints were absent. CONCLUSION: Transcanalicular
      endoscopy of the lacrimal duct system should not be regarded as the means of
      choice but it does offer additional diagnostic and therapeutic options for
      special indications. A main advantage of this kind of surgery is its minimally
      invasive character. Under visual control, topographic anatomy can be preserved.
      Dacryoendoscopy in children should be done only by experienced surgeons.

PMID- 25851052
TI  - Efficacy of maternal tenofovir disoproxil fumarate in interrupting mother-to
      infant transmission of hepatitis B virus.
AB  - The efficacy and safety of maternal tenofovir disoproxil fumarate (TDF) in
      reducing mother-to-infant hepatitis B virus (HBV) transmissions is not clearly
      understood. We conducted a prospective, multicenter trial and enrolled 118
      hepatitis B surface antigen (HBsAg)- and hepatitis B e antigen-positive pregnant
      women with HBV DNA >=7.5 log10 IU/mL. The mothers received no medication (control
      group, n = 56, HBV DNA 8.22 +/- 0.39 log10 IU/mL) or TDF 300 mg daily (TDF group,
      n = 62, HBV DNA 8.18 +/- 0.47 log10 IU/mL) from 30-32 weeks of gestation until 1
      month postpartum. Primary outcome was infant HBsAg at 6 months old. At delivery,
      the TDF group had lower maternal HBV DNA levels (4.29 +/- 0.93 versus 8.10 +/-
      0.56 log10 IU/mL, P < 0.0001). Of the 121/123 newborns, the TDF group had lower
      rates of HBV DNA positivity at birth (6.15% versus 31.48%, P = 0.0003) and HBsAg
      positivity at 6 months old (1.54% versus 10.71%, P = 0.0481). Multivariate
      analysis revealed that the TDF group had lower risk (odds ratio = 0.10, P =
      0.0434) and amniocentesis was associated with higher risk (odds ratio 6.82, P =
      0.0220) of infant HBsAg positivity. The TDF group had less incidence of maternal
      alanine aminotransferase (ALT) levels above two times the upper limit of normal
      for >=3 months (3.23% versus 14.29%, P = 0.0455), a lesser extent of postpartum
      elevations of ALT (P = 0.007), and a lower rate of ALT over five times the upper
      limit of normal (1.64% versus 14.29%, P = 0.0135) at 2 months postpartum.
      Maternal creatinine and creatinine kinase levels, rates of congenital anomaly,
      premature birth, and growth parameters in infants were comparable in both groups.
      At 12 months, one TDF-group child newly developed HBsAg positivity, presumably
      due to postnatal infection and inefficient humoral responses to vaccines.
      CONCLUSIONS: Treatment with TDF for highly viremic mothers decreased infant HBV
      DNA at birth and infant HBsAg positivity at 6 months and ameliorated maternal ALT
      elevations. (Hepatology 2015;62:375-386.

PMID- 25851055
TI  - Reagent pencils: a new technique for solvent-free deposition of reagents onto
      paper-based microfluidic devices.
AB  - Custom-made pencils containing reagents dispersed in a solid matrix were
      developed to enable rapid and solvent-free deposition of reagents onto membrane
      based fluidic devices. The technique is as simple as drawing with the reagent
      pencils on a device. When aqueous samples are added to the device, the reagents
      dissolve from the pencil matrix and become available to react with analytes in
      the sample. Colorimetric glucose assays conducted on devices prepared using
      reagent pencils had comparable accuracy and precision to assays conducted on
      conventional devices prepared with reagents deposited from solution. Most
      importantly, sensitive reagents, such as enzymes, are stable in the pencils under
      ambient conditions, and no significant decrease in the activity of the enzyme
      horseradish peroxidase stored in a pencil was observed after 63 days. Reagent
      pencils offer a new option for preparing and customizing diagnostic tests at the
      point of care without the need for specialized equipment. 

PMID- 25851054
TI  - Overexpression of Nrf2 attenuates Carmustine-induced cytotoxicity in U87MG human
      glioma cells.
AB  - BACKGROUND: Malignant glioma is one of the most devastating tumors in adults with
      poor patient prognosis. Notably, glioma often exhibits resistance to conventional
      chemotherapeutic approaches, complicating patient treatments. However, the
      molecular mediators involved in tumor chemoresistance remain poorly defined,
      creating a barrier to the successful management of glioma. In the present study,
      we hypothesized that the antioxidant transcription factor, Nrf2 (nuclear factor
      erythroid-derived 2 like 2), attenuates glioma cytotoxicity to Carmustine (BCNU),
      a widely used chemotherapeutic agent known to modulate cellular oxidative
      balance. METHODS: To test the hypothesis, we employed human malignant glioma cell
      line, U87MG and overexpression of Nrf2 in glioma cells was achieved using both
      pharmacological and genetic approaches. RESULTS: Notably, induction of Nrf2 was
      associated with increased expression of heme oxygenase-1 (HO-1), a stress
      inducible enzyme involved in anti-oxidant defense. In addition, over expression
      of Nrf2 in U87MG cells significantly attenuated the cytotoxicity of Carmustine as
      evidenced by both cellular viability assay and flow cytometry analysis.
      Consistent with this, antioxidants such as glutathione and N-acetyl cysteine
      significantly reduced Carmustine mediated glioma cytotoxicity. CONCLUSIONS: Taken
      together, these data strongly implicate an unexplored role of Nrf2 in glioma
      resistance to Carmustine and raise the possible use of Nrf2 inhibitors as adjunct
      to Carmustine for the treatment of malignant glioma.

PMID- 25851056
TI  - Predictive classification of correlated targets with application to detection of
      metastatic cancer using functional CT imaging.
AB  - Perfusion computed tomography (CTp) is an emerging functional imaging modality
      that uses physiological models to quantify characteristics pertaining to the
      passage of fluid through blood vessels. Perfusion characteristics provide
      physiological correlates for neovascularization induced by tumor angiogenesis.
      Thus CTp offers promise as a non-invasive quantitative functional imaging tool
      for cancer detection, prognostication, and treatment monitoring. In this article,
      we develop a Bayesian probabilistic framework for simultaneous supervised
      classification of multivariate correlated objects using separable covariance. The
      classification approach is applied to discriminate between regions of liver that
      contain pathologically verified metastases from normal liver tissue using five
      perfusion characteristics. The hepatic regions tend to be highly correlated due
      to common vasculature. We demonstrate that simultaneous Bayesian classification
      yields dramatic improvements in performance in the presence of strong correlation
      among intra-subject units, yet remains competitive with classical methods in the
      presence of weak or no correlation. 

PMID- 25851057
TI  - The interaction between self-bias and reward: Evidence for common and distinct
      processes.
AB  - The perceptual matching of shapes and labels can be affected by both self- and
      reward-biases when shapes are linked either to labels referring to particular
      individuals (you, friend, stranger) or to different reward values (L8, L2, L0).
      We investigated the relations between these biases by varying the reward value
      associated with particular shape-label pairs (circle-you, square-friend, triangle
      stranger). Self shape-label pairs (circle-you) always received no reward, while
      friend shape-label pairs (square-friend) received high reward and stranger shape
      label pairs low reward (triangle-stranger), or the reverse (friend-low reward;
      stranger-high reward). Despite receiving no reward, responses to self-related
      pairs were advantaged relative to those to low-reward stimuli and did not differ
      from those to high-reward items. There was also an advantage for responses to
      high-reward friend pairs relative to low-reward stranger stimuli, and for high
      reward stranger stimuli compared to low-reward friends. Correlations across
      individuals were found across trial blocks for both the self-advantage and the
      high-reward advantage, but the self- and reward-advantages were uncorrelated.
      This suggests that the self- and reward-advantage effects have different origins.
      In addition, the magnitude of the self-advantage varied according to the rated
      personal distance between a participant and a stranger. For individuals
      manifesting a close personal distance to strangers, the self-advantage was
      smaller, and sensitivity to reward influenced the difference between the self-
      and high-reward conditions. For individuals manifesting a large personal distance
      to strangers, sensitivity to reward did not affect self-matching. We suggest that
      self-advantages on perceptual matching arise independent of reward for
      individuals with a large personal distance to strangers. On the other hand, in
      individuals with a weak self-bias, high reward and the self modulate a common
      subjective value system. 

PMID- 25851058
TI  - Remote surveillance after colorectal cancer surgery: an effective alternative to
      standard clinic-based follow-up.
AB  - AIM: Most colorectal cancer recurrences are asymptomatic and are detected through
      routine postoperative clinic surveillance programmes with associated
      investigations. However, attendance at these clinics has a financial cost and may
      be associated with an increase in patient anxiety and dissatisfaction. The
      results of a remote follow-up system developed for selected patients are
      reported. METHOD: A remote surveillance programme has been in place in our
      institution for over 9 years. Patients having elective and emergency treatment
      for colorectal cancer were enrolled. The timeliness of the investigation,
      detection of local recurrence and distant metastases and overall 5-year survival
      rates were determined. A cost review and patient satisfaction survey were
      performed. RESULTS: The programme was suitable for over 900 patients who had
      received surgery for colorectal cancer between 2004 and 2012, representing some
      50% of the total number of patients treated in this period. Of these, 811 (90%)
      had investigations carried out on time. Five-year survival rates were comparable
      with national data. Cost-minimization analysis demonstrated a financial saving of
      63% and a 75% reduction in clinic appointments. High levels of overall patient
      satisfaction (97%) were noted with the programme. CONCLUSION: A remote
      surveillance system after colorectal cancer surgery is a safe and cost-effective
      alternative to traditional clinic-based follow up and has high patient
      satisfaction.

PMID- 25851059
TI  - Efficacy of 1% acetic acid in the treatment of chronic wounds infected with
      Pseudomonas aeruginosa: prospective randomised controlled clinical trial.
AB  - : Chronic wounds are those wounds that are persistent and do not respond to any
      sort of treatment. The concept of using topical antiseptics on open wounds is to
      prevent and treat infections. They also help to shorten the time taken to heal
      the wounds. The use of topical agents on wounds to prevent infection is a minimal
      ability to develop resistance to the microorganisms. Pseudomonas aeruginosa is a
      Gram-negative opportunistic pathogen with innate resistance to many antibiotics.
      In places that are economically backward, these problems get compounded by the
      inability of patients to afford newer expensive drugs. Topically applied dilute
      acetic acid, which is cheap and easily available, has been found to be effective
      in such chronic wounds. In the present study, an attempt has been made to use 1%
      acetic acid as the sole antimicrobial agent for the treatment of pseudomonal
      wound infections. A control limb was used in which the wounds were treated with
      normal saline. Our objective was to evaluate the efficacy of acetic acid in low
      concentration of 1% in chronic wounds infected with P. aeruginosa. This was a
      prospective study conducted over a period of 6 months. INCLUSION CRITERIA: All
      patients with chronic wounds infected with P. aeruginosa. EXCLUSION CRITERIA:
      Wounds due to massive burns, suspected malignancy, immunocompromised individuals
      and individuals with sepsis. A total of 32 patients enrolled in the study.
      Subjects were randomised equally to the 1% acetic acid group and saline dressing
      group. None of the patients received any systemic antibiotics during the study
      period and received twice daily dressings. The endpoint of the treatment was
      wounds free of P. aeruginosa. The duration of treatment required to eliminate the
      Pseudomonas from the wounds in the acetic acid group was on an average 7 days
      less than that required by the saline group. P value was <0.001. In the 1% acetic
      acid group irrespective of the sensitivity of the organism to antibiotics,
      Pseudomonas organisms were eliminated within the same time period - 4.5 days. In
      the saline group, susceptible organisms were eliminated within 11.5 days and
      multidrug-resistant organisms were eliminated by 15.5 days. 1% acetic acid is a
      simple, safe and effective topical antiseptic that can be used in the elimination
      of P. aeruginosa from chronic infected wounds.

PMID- 25851060
TI  - Safety and immunogenicity of a soluble native Neospora caninum tachyzoite-extract
      vaccine formulated with a soy lecithin/beta-glucan adjuvant in pregnant cattle.
AB  - The global economic impact of Neospora caninum infection in cattle herds has
      promoted the development of vaccines that can be safely used during pregnancy.
      The aim of this study was to evaluate the safety and immunogenicity of a vaccine
      formulated with the soluble fraction of tachyzoite's lysate and a soy-based
      aqueous adjuvant (sNcAg/AVEC), which was protective in the mouse model and
      induced strong IFN-gamma responses and high avidity antibodies in non-pregnant
      cattle. Ten pregnant heifers were vaccinated twice during the first trimester of
      gestation and 8 remained unvaccinated. Anti-N. caninum immune responses were
      efficiently primed by vaccination, evidenced by a quick induction of IgM serum
      titers (7dpv) and a prompt switch to high avidity IgG shortly after infection
      (performed at 78 or 225 days of gestation; n=5 each); while naive cattle elicited
      lower IgG titers, with a delayed kinetics. High systemic IFN-gamma levels were
      induced after infection which did not interfere with pregnancy. No local or
      systemic adverse effects were recorded along the study. Calves were born in term
      and in good health conditions, showing that the sNcAg/AVEC vaccine was safe when
      applied to healthy heifers during the first trimester of gestation. 

PMID- 25851062
TI  - Shortened length of hospital stay with rivaroxaban in patients with symptomatic
      venous thromboembolism in Japan: the J-EINSTEIN pulmonary embolism and deep vein
      thrombosis program.
AB  - BACKGROUND: In Japan, the standard of care for the treatment of pulmonary
      embolism (PE) and/or deep vein thrombosis (DVT) consists of intravenous
      unfractionated heparin (UFH) followed by warfarin, which was recently compared
      with rivaroxaban, an oral factor Xa inhibitor, in randomized trials. AIM: To
      examine the length of hospital stay in patients with PE and/or DVT receiving
      rivaroxaban compared to Japanese standard therapy in the Japanese (J)-EINSTEIN PE
      and DVT program. METHODS: Open-label, randomized clinical trials that compared 3,
      6, or 12 months of rivaroxaban with UFH and warfarin in patients with acute,
      confirmed symptomatic proximal PE and/or DVT. Decisions regarding hospital
      admission and/or discharge were left to the clinical judgment of attending
      physicians. Analyses were conducted in the intention-to-treat (ITT) population.
      RESULTS: In the ITT population (N = 97), overall patient characteristics were
      similar in both treatment arms. The median length of stay in rivaroxaban patients
      was 10.0 days (interquartile range [IQR] 6.0 to 15.0 days) while it was 15.0 days
      (IQR 9.0 to 22.0) for patients on standard therapy (p = 0.016). All of the four
      DVT patients who were not hospitalized for the index event were in the
      rivaroxaban arm. CONCLUSIONS: Our results suggest that treatment with rivaroxaban
      may significantly reduce the length of hospital stay in patients hospitalized for
      PE and/or DVT compared with the current standard of care in Japan, thereby
      reducing the burden on patients and the healthcare system. The limitations of our
      study include small sample size and the generalizability of the findings to the
      real-world setting. Further research is warranted to identify PE and/or DVT
      patients in Japanese clinical practice who may potentially be managed as
      outpatients. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01516814 and NCT01516840.

PMID- 25851063
TI  - Persistent topology for cryo-EM data analysis.
AB  - In this work, we introduce persistent homology for the analysis of cryo-electron
      microscopy (cryo-EM) density maps. We identify the topological fingerprint or
      topological signature of noise, which is widespread in cryo-EM data. For low
      signal-to-noise ratio (SNR) volumetric data, intrinsic topological features of
      biomolecular structures are indistinguishable from noise. To remove noise, we
      employ geometric flows that are found to preserve the intrinsic topological
      fingerprints of cryo-EM structures and diminish the topological signature of
      noise. In particular, persistent homology enables us to visualize the gradual
      separation of the topological fingerprints of cryo-EM structures from those of
      noise during the denoising process, which gives rise to a practical procedure for
      prescribing a noise threshold to extract cryo-EM structure information from noise
      contaminated data after certain iterations of the geometric flow equation. To
      further demonstrate the utility of persistent homology for cryo-EM data analysis,
      we consider a microtubule intermediate structure Electron Microscopy Data (EMD
      1129). Three helix models, an alpha-tubulin monomer model, an alpha-tubulin and
      beta-tubulin model, and an alpha-tubulin and beta-tubulin dimer model, are
      constructed to fit the cryo-EM data. The least square fitting leads to similarly
      high correlation coefficients, which indicates that structure determination via
      optimization is an ill-posed inverse problem. However, these models have
      dramatically different topological fingerprints. Especially, linkages or
      connectivities that discriminate one model from another, play little role in the
      traditional density fitting or optimization but are very sensitive and crucial to
      topological fingerprints. The intrinsic topological features of the microtubule
      data are identified after topological denoising. By a comparison of the
      topological fingerprints of the original data and those of three models, we found
      that the third model is topologically favored. The present work offers persistent
      homology based new strategies for topological denoising and for resolving ill
      posed inverse problems.

PMID- 25851064
TI  - Polycyclic aromatic hydrocarbon concentrations in gas and particle phases and
      source determination in atmospheric samples from a semiurban area of Dourados,
      Brazil.
AB  - A headspace solid-phase microextraction (HS-SPME) procedure that employs a
      PDMS/DVB fiber was developed for the analysis of gas-phase polycyclic aromatic
      hydrocarbons (PAHs) collected in polyurethane foam (PUF) by gas chromatography
      (GC) mass spectrometry. The method exhibited good linearity (R (2) > 0.99) and
      repeatability (4.9-25 %) as well as an impressive detection limit that ranged
      from 1.1 to 3.3 ng. Twenty-two air samples were collected by high-volume samplers
      from January to November 2007 in a semiurban area of Dourados (Brazil) and were
      analyzed for their content of total suspended particulates and PAHs. The PAHs
      were extracted from the PUF samples using the developed procedure (HS-SPME), and
      PAHs adsorbed on particulate matter were extracted with dichloromethane/methanol
      (4:1 [v/v]) in an ultrasonic bath. The values of the total daily concentrations
      of 16 PAHs determined in the samples ranged from 0.375 to 8.407 ng m(-3). In
      addition, diagnostic ratios were calculated, showing that the PAHs in the
      atmosphere at the sampling site originated predominantly from vehicle emissions
      and the combustion of grass and wood. Hierarchical cluster analysis and principal
      component analysis were performed as well, the results of which indicated (1) the
      same sources of PAH identified by the diagnostic ratios and (2) that the sampling
      days could be categorized into three groups depending on the atmospheric
      conditions. GC retention indices were also used to identify PAHs, biphenyl
      (phenylbenzene), and heterocyclic organic compounds (benzofurans) in some of the
      samples.

PMID- 25851065
TI  - Research Synthesis and the Value per Statistical Life.
AB  - The value of small changes in mortality risk, conventionally expressed as the
      value per statistical life (VSL), is a major determinant of the benefits of many
      environmental, health, and safety regulations and other policies. However,
      selecting an appropriate value is challenging. Different studies yield different
      results and analysts often find they lack estimates that are directly applicable
      to the policy they are assessing. Research-synthesis methods are widely used to
      address these concerns in many fields, yet we find only limited applications to
      estimating VSL. More structured, criteria-driven review of the available studies
      is an important first step. Additional meta-analyses that use such review as a
      starting point are needed to explore variation across studies as well as to
      adjust estimates to better fit different policy contexts. Carefully designed
      expert elicitation is significantly underutilized and is particularly important
      when the available research is limited or inconsistent. Although greater use of
      such methods is likely to enhance the credibility of the VSL estimates applied in
      policy analyses, as well as provide greater insights into the advantages and
      limitations of the available research, it is not clear how much the resulting
      estimates will vary from those currently used. In the United States, these
      estimates are generally around $9 million. 

PMID- 25851066
TI  - The BMJ report on mortality cuts in hospitals put into special measures in 2013
      is misleading.

PMID- 25851067
TI  - Bio-inspired artificial functional photocatalyst: biomimetic enzyme-like
      TiO2/reduced graphene oxide nanocomposite with excellent molecular recognition
      ability.
AB  - An enzyme-like TiO(2)/reduced graphene oxide (enzyme-TiO(2)/rGO) nanocomposite
      with molecular recognition ability was fabricated by biomimicking the geometrical
      and chemical complementation of the enzyme and substrate. The anatase TiO(2)
      nanocrystals were densely dispersed on rGO nanosheets with close interfacial
      contacts. With geometrical and chemical matching of target molecules and
      memorized cavities, the adsorption capacity of enzyme-TiO(2)/rGO nanocomposites
      for 4-nitrophenol (4.71 mg g(-1)) is about six times that of control TiO(2)/rGO
      without the enzyme-like feature (0.79 mg g(-1)), and the enzyme-TiO(2)/rGO shows
      a relative selectivity coefficient of 7.24. Moreover, enzyme-TiO(2)/rGO exhibits
      molecular recognitive photocatalytic degradation for a particular contaminant.
      The results demonstrate that enzyme-substrate recognition provides a convenient
      and powerful basis on which to biomimic and construct efficient photocatalysts
      with high selectivity.

PMID- 25851068
TI  - Cytoprotective and Anti-secretory Effects of Azadiradione Isolated from the Seeds
      of Azadirachta indica (neem) on Gastric Ulcers in Rat Models.
AB  - Azadirachta indica is well known medicinal plant mentioned in ancient herbal
      texts. It has been extensively used in Ayurvedic, Unani and Homoeopathic medicine
      and has become a luminary of modern medicine. As part of our drug discovery
      program we isolated azadiradione from the ethanolic extract of seeds of A. indica
      and evaluated for in-vivo antiulcer activity in cold restraint induced gastric
      ulcer model, aspirin induced gastric ulcer model, alcohol induced gastric ulcers
      model and pyloric ligation induced ulcer model. Azadiradione exhibited potent
      antiulcer activity through the inhibition of H+ K+-ATPase (proton pump) activity
      via its cytoprotective effect and also via its antisecretory effect. This
      combined effect has valuable potential in the future treatment of peptic
      ulceration.

PMID- 25851069
TI  - Increased Prevalence and Resistance of Important Pathogens Recovered from
      Respiratory Specimens of Cystic Fibrosis Patients During a Decade.
AB  - BACKGROUND: The study objective was to identify changes of prevalence and
      resistance of important pathogens in specimens of cystic fibrosis (CF) patients
      within a decade. METHODS: Samples of 94 patients, who attended 2 CF centers from
      2001 to 2011 were retrospectively analyzed. RESULTS: Staphylococcus aureus was
      the most prevalent organism (74.5% in 2011) with an increase of methicillin
      resistant S. aureus in patients (0% vs. 9.6%, n = 9). Resistance of S. aureus to
      gentamicin decreased (41.8% vs. 21%; P < 0.001), whereas resistance to rifampicin
      and trimethoprim/sulfamethoxazole (P < 0.05) increased significantly with a trend
      to increased resistance to clindamycin and erythromycin (P = 0.063). Methicillin
      resistant S. aureus isolates belonged to 6 spa types (t003, t008, t011, t034,
      t045, t548). There was a significant increase of Pseudomonas aeruginosa
      prevalence (63.8% in 2011 vs. 46.8% in 2001, P = 0.019). Resistance of P.
      aeruginosa increased significantly to imipenem, gentamicin, amikacin, tobramycin,
      ciprofloxacin and fosfomycin, whereas resistance to piperacillin-tazobactam,
      meropenem and aztreonam decreased. Significantly fewer Stenotrophomonas
      maltophilia isolates were susceptible to all the analyzed antibiotics
      (trimethoprim/sulfamethoxazole, ciprofloxacin and colistin) in 2011 compared with
      2001 (13.5% vs. 42.1%; P = 0.023), whereas the resistance to colistin increased
      significantly (11.1% vs. 62.2%; P < 0.001). Burkholderia cepacia complex and
      nontuberculous mycobacteria were not detected in 2001 but in 2011 in 7.4% (n = 9)
      and 7.4% (n = 9) of patients, respectively. B. cepacia complex isolates belonged
      to 8 multilocus sequence types. CONCLUSIONS: Our retrospective analysis revealed
      an increase of important CF-related pathogens, the emergence of new pathogens and
      a substantial increase of multidrug-resistant CF-specific isolates. Our findings
      are of importance to clinicians for the alertness of local epidemiology, which
      may be useful for prevention and treatment strategies.

PMID- 25851070
TI  - Antiretroviral Therapy Use During Pregnancy and the Risk of Small for Gestational
      Age Birth in a Medicaid Population.
AB  - BACKGROUND: Several studies have assessed the association between antiretroviral
      (ARV) therapy use during pregnancy and small for gestational age (SGA), but the
      evidence remains incompletely elucidated. METHODS: We linked data from Tennessee
      Medicaid files and vital records to evaluate pregnancies among human
      immunodeficiency virus (HIV)-infected women who delivered between 1994 and 2009.
      Maternal HIV status was defined based on diagnosis codes, ARV prescriptions and
      laboratory codes for CD4 count or HIV RNA assays. ARV use was identified from
      pharmacy claims. Risk of SGA (defined as birth weight below the 10th percentile
      for gestational age) and preterm birth was evaluated using logistic regression
      models. RESULTS: Four hundred and seventy-seven HIV-infected pregnant women
      contributing 604 singleton pregnancies were identified; 156 (26%) delivered SGA
      infants. ARV use during pregnancy was not associated with SGA [adjusted odds
      ratio: 0.93; 95% confidence interval (CI): 0.56-1.56] or preterm birth (adjusted
      odds ratio: 0.74; 95% CI: 0.42-1.32). Exposure to a protease inhibitor during the
      first trimester was associated with a lower risk of SGA (odds ratio: 0.54; 95%
      CI: 0.29-1.01) compared with non-exposure to a protease inhibitor throughout
      pregnancy. CONCLUSIONS: We observed no evidence of an association between ARV
      exposure during pregnancy and SGA delivery in this Medicaid cohort of HIV
      infected women.

PMID- 25851071
TI  - False-positive (1,3) beta-D-glucan assay in a patient with intracranial
      germinoma.

PMID- 25851072
TI  - Use of paracetamol during pregnancy and child neurological development.
AB  - Paracetamol (acetaminophen) remains the first line for the treatment of pain and
      fever in pregnancy. Recently published epidemiological studies suggested a
      possible association between paracetamol exposure in utero and attention-deficit
      hyperactivity disorder/hyperkinetic disorder (ADHD/HKD) or adverse development
      issues in children. However, the effects observed are in the weak to moderate
      range, and limitations in the studies' design prevent inference on a causal
      association with ADHD/HKD or child neurological development. In parallel, recent
      animal data showed that cognition and behaviour may be altered following exposure
      to therapeutic doses of paracetamol during early development. These effects may
      be mediated by interference of paracetamol with brain-derived neurotrophic
      factor, neurotransmitter systems (including serotonergic, dopaminergic,
      adrenergic, as well as the endogenous endocannabinoid systems), or cyclooxygenase
      2. However, no firm conclusion can be made on the relevance of these observations
      to humans. We conclude that additional well-designed cohort studies are necessary
      to confirm or disprove the association. In the context of current knowledge,
      paracetamol is still to be considered safe in pregnancy and should remain the
      first-line treatment for pain and fever. 

PMID- 25851073
TI  - Implementation of the National Nursing Quality Report Initiative in Canada:
      Insights From Pilot Participants.
AB  - A qualitative study was undertaken to explore the perceptions and experiences of
      nurse leaders associated with their participation in the pilot testing of a
      national nursing database. Interviews with 18 participants were conducted and
      analyzed using a direct content analysis approach. Three themes emerged including
      selecting, accessing, and uploading indicators; using indicators and monitoring
      tools for improvement; and perceiving involvement as a catalyst. Study findings
      may inform quality improvement efforts in health care organizations. 

PMID- 25851074
TI  - Tests of Eustachian tube function: a review.
AB  - BACKGROUND: Eustachian tube (ET) dysfunction is a common but poorly understood
      cause of patient symptoms, and an important aetiological factor in the
      development of middle ear pathology. Despite this, there are no specific tests of
      ET function in widespread clinical use and no identified 'gold standard' with
      which to diagnose the disease. OBJECTIVE: This review aims to review the
      literature to identify currently available tests of ET function and, where
      possible, report on their accuracy. TYPE OF REVIEW: Narrative systematic review.
      SEARCH STRATEGY: MEDLINE, EMBASE, Biosis and the Cochrane library were searched
      and reference lists reviewed for relevant articles. EVALUATION METHOD: Tests in
      included studies were required to measure a physiological function of the ET, or
      play a role in the diagnosis of poor ET function. Significant variation in
      demographic characteristics, disease presentation and severity, and technological
      approaches only permitted narrative systematic review. RESULTS: While many tests
      of ET function have been developed, with some in routine clinical use, all have
      significant limitations. Published accuracy data are limited and of differing
      quality due to the variability incomparative tests, and the spectrum of
      otological disorders associated with ET dysfunction. CONCLUSIONS: Currently, no
      single test could be considered a 'gold standard' for the diagnosis of ET
      dysfunction, but there is some evidence that diagnostic accuracy can be improved
      by combining the results of different objective tests and patient-reported
      outcome measures. Further development of ET function tests is required to
      facilitate the accurate diagnosis of patients and allow outcome reporting for new
      interventions.

PMID- 25851075
TI  - Amplitude Modulation Detection and Speech Recognition in Late-Implanted
      Prelingually and Postlingually Deafened Cochlear Implant Users.
AB  - OBJECTIVES: Many late-implanted prelingually deafened cochlear implant (CI)
      patients struggle to obtain open-set speech understanding. Because it is known
      that low-frequency temporal-envelope information contains important cues for
      speech understanding, the goal of this study was to compare the temporal-envelope
      processing abilities of late-implanted prelingually and postlingually deafened CI
      users. Furthermore, the possible relation between temporal processing abilities
      and speech recognition performances was investigated. DESIGN: Amplitude
      modulation detection thresholds were obtained in eight prelingually and 18
      postlingually deafened CI users, by means of a sinusoidally modulated broadband
      noise carrier, presented through a loudspeaker to the CI user's clinical device.
      Thresholds were determined with a two-down-one-up three-interval oddity adaptive
      procedure, at seven modulation frequencies. Phoneme recognition (consonant
      nucleus-consonant [CNC]) scores (percentage correct at 65 dB SPL) were gathered
      for all CI users. For the prelingually deafened group, scores on two additional
      speech tests were obtained: (1) a closed-set monosyllable-trochee-spondee test
      (percentage correct scores at 65 dB SPL on word recognition and categorization of
      the suprasegmental word patterns), and (2) a speech tracking test (number of
      correctly repeated words per minute) with texts specifically designed for this
      population. RESULTS: The prelingually deafened CI users had a significantly lower
      sensitivity to amplitude modulations than the postlingually deafened CI users,
      and the attenuation rate of their temporal modulation transfer function (TMTF)
      was greater. None of the prelingually deafened CI users were able to detect
      modulations at 150 and 200 Hz. High and significant correlations were found
      between the results on the amplitude modulation detection test and CNC phoneme
      scores, for the entire group of CI users. In the prelingually deafened group, CNC
      phoneme scores, word scores on the monosyllable-trochee-spondee test, and speech
      tracking scores correlated significantly with the mean amplitude modulation
      detection threshold of the modulation frequencies between 5 and 100 Hz and with
      almost all separate amplitude modulation thresholds. High correlations with these
      speech measures were also found for the attenuation rate of and the surface area
      below the TMTF. In postlingually deafened CI users, CNC phoneme scores only
      correlated significantly with the 100-Hz and 150-Hz amplitude modulation
      thresholds, as well as with the attenuation rate of and surface area below the
      TMTF. CONCLUSIONS: Prelingually deafened CI users were less sensitive to temporal
      modulations than postlingually deafened CI users, and the attenuation rate of
      their TMTF was steeper. For all CI users, subjects with better amplitude
      modulation detection skills tended to score better on measures of speech
      understanding. Significant correlations with low modulation frequencies were
      found only for the prelingually deafened CI users and not for the postlingually
      deafened CI users.

PMID- 25851076
TI  - Decisional support to prevent adverse drug reactions of long latency: pilot
      randomized controlled intervention for glucocorticoid-induced diabetes.
AB  - RATIONALE, AIMS, AND OBJECTIVES: Long-term exposure to glucocorticoids can cause
      adverse drug reactions of long latency (ADRLLs), including glucocorticoid-induced
      diabetes mellitus (GID). Providers can monitor for GID using the glycosylated
      haemoglobin blood (HbA1C) test. This study examined the utility of decisional
      support to improve HbA1C-based screening for GID. US veterans were identified as
      chronic users of oral glucocorticoids (>120 days of oral glucocorticoids in the
      last 2 years). The primary care providers caring for these patients were the
      target of the intervention. Providers were randomized to receive automatic HbA1C
      orders for their patients receiving chronic glucocorticoid or usual care.
      METHODS: This study was a pilot two-arm, group-randomized, controlled trial (n =
      12 providers, n = 38 patients). Data collection occurred from 5 May 2013 until 10
      January 2014. A pharmacist generated the order for an HbA1C through the
      electronic medical record. The time between the intervention start date and the
      date on which an HbA1C order was signed were compared using Cox proportional and
      hierarchical linear regression. RESULTS: The time to sign HbA1C orders (mean 12.0
      days for the intervention arm; 104.0 days for control arm) was associated with
      significant differences favouring the intervention [HR (Hazard Ratio) 50.2, P <
      0.001, confidence interval (CI) 6.3 to 398.7]. For the intervention group, 95% of
      orders were signed, whereas only 12% of control providers signed orders (odds
      ratio 150, P < 0.001, CI 12.4 to 1812.9). CONCLUSIONS: The results of this study
      strongly suggest that the clinical pharmacist-triggered order intervention is
      effective. This method of computerized decisional support may be useful in
      improving screening for GID and ADRLLs.

PMID- 25851077
TI  - Differences in performance and transcriptome-wide gene expression associated with
      Rhagoletis (Diptera: Tephritidae) larvae feeding in alternate host fruit
      environments.
AB  - Host race formation, the establishment of new populations using novel resources,
      is a major hypothesized mechanism of ecological speciation, especially in plant
      feeding insects. The initial stages of host race formation will often involve
      phenotypic plasticity on the novel resource, with subsequent genetically based
      adaptations enhancing host-associated fitness differences. Several studies have
      explored the physiology of the plastic responses of insects to novel host
      environments. However, the mechanisms underlying evolved differences among host
      races and species remain poorly understood. Here, we demonstrate a reciprocal
      larval performance difference between two closely related species of Rhagoletis
      flies, R. pomonella and R. zephyria, specialized for feeding in apple and
      snowberry fruit, respectively. Microarray analysis of fly larvae feeding in
      apples versus snowberries revealed patterns of transcriptome-wide differential
      gene expression consistent with both plastic and evolved responses to the
      different fruit resources, most notably for detoxification-related genes such as
      cytochrome p450s. Transcripts exhibiting evolved expression differences between
      species tended to also demonstrate plastic responses to fruit environment. The
      observed pattern suggests that Rhagoletis larvae exhibit extensive plasticity in
      gene expression in response to novel fruit that may potentiate shifts to new
      hosts. Subsequent selection, particularly selection to suppress initially costly
      plastic responses, could account for the evolved expression differences observed
      between R. pomonella and R. zephyria, creating specialized races and new fly
      species. Thus, genetically based ecological adaptations generating new
      biodiversity may often evolve from initial plastic responses in gene expression
      to the challenges posed by novel environments. 

PMID- 25851078
TI  - The influence of prenatal intimate partner violence exposure on hypothalamic
      pituitary-adrenal axis reactivity and childhood internalizing and externalizing
      symptoms.
AB  - This prospective longitudinal study examines the long-term influence of intimate
      partner violence (IPV) exposure in utero. We hypothesized that (a) prenatal IPV
      increases risk for internalizing and externalizing problems as well as for a
      profile of dysregulated cortisol reactivity, and (b) patterns of cortisol hyper-
      and hyporeactivity are differentially associated with internalizing and
      externalizing problems. The participants were 119 10-year-old children. Their
      mothers reported their IPV experiences and distress during pregnancy. Child and
      maternal reports of internalizing and externalizing problems as well as lifetime
      IPV exposure were obtained. Salivary cortisol was assessed at baseline, 20 min,
      and 40 min after challenge. The results partially supported our hypotheses:
      Exposure to IPV during pregnancy predicted child-reported internalizing and
      externalizing problems, mother ratings of child externalizing problems, and a
      profile of high cortisol secretion before and after stress challenge. The results
      were significant above and beyond the influence of maternal distress during
      pregnancy and IPV that occurred during the child's life. In addition, a profile
      of high cortisol secretion was associated with maternal reports of child
      internalizing behaviors. Findings support the growing consensus that prenatal
      stress can lead to lasting disruptions in adaptation and highlight the need for
      more longitudinal examinations of prenatal IPV exposure. 

PMID- 25851079
TI  - The influence of electromyographic recording methods and the innervation zone on
      the mean power frequency-torque relationships.
AB  - This study examined the effects of electromyographic (EMG) recording methods and
      innervation zone (IZ) on the mean power frequency (MPF)-torque relationships.
      Nine subjects performed isometric ramp muscle actions of the leg extensors from
      5% to 100% of maximal voluntary contraction with an eight channel linear
      electrode array over the IZ of the vastus lateralis. The slopes were calculated
      from the log-transformed monopolar and bipolar EMG MPF-torque relationships for
      each channel and subject and 95% confidence intervals (CI) were constructed
      around the slopes for each relationship and the composite of the slopes. Twenty
      two to 55% of the subjects exhibited 95% CIs that did not include a slope of zero
      for the monopolar EMG MPF-torque relationships while 25-75% of the subjects
      exhibited 95% CIs that did not include a slope of zero for the bipolar EMG MPF
      torque relationships. The composite of the slopes from the EMG MPF-torque
      relationships were not significantly different from zero for any method or
      channel, however, the method and IZ location slightly influenced the number of
      significant slopes on a subject-by-subject basis. The log-transform model
      indicated that EMG MPF-torque patterns were nonlinear regardless of recording
      method or distance from the IZ. 

PMID- 25851080
TI  - Changes in hippocampal synaptic functions and protein expression in monosodium
      glutamate-treated obese mice during development of glucose intolerance.
AB  - Glucose is the sole neural fuel for the brain and is essential for cognitive
      function. Abnormalities in glucose tolerance may be associated with impairments
      in cognitive function. Experimental obese model mice can be generated by an
      intraperitoneal injection of monosodium glutamate (MSG; 2 mg/g) once a day for 5
      days from 1 day after birth. MSG-treated mice have been shown to develop glucose
      intolerance and exhibit chronic neuroendocrine dysfunction associated with marked
      cognitive malfunctions at 28-29  weeks old. Although hippocampal synaptic
      plasticity is impaired in MSG-treated mice, changes in synaptic transmission
      remain unknown. Here, we investigated whether glucose intolerance influenced
      cognitive function, synaptic properties and protein expression in the
      hippocampus. We demonstrated that MSG-treated mice developed glucose intolerance
      due to an impairment in the effectiveness of insulin actions, and showed
      cognitive impairments in the Y-maze test. Moreover, long-term potentiation (LTP)
      at Schaffer collateral-CA1 pyramidal synapses in hippocampal slices was impaired,
      and the relationship between the slope of extracellular field excitatory
      postsynaptic potential and stimulus intensity of synaptic transmission was weaker
      in MSG-treated mice. The protein levels of vesicular glutamate transporter 1 and
      GluA1 glutamate receptor subunits decreased in the CA1 region of MSG-treated
      mice. These results suggest that deficits in glutamatergic presynapses as well as
      postsynapses lead to impaired synaptic plasticity in MSG-treated mice during the
      development of glucose intolerance, though it remains unknown whether impaired
      LTP is due to altered inhibitory transmission. It may be important to examine
      changes in glucose tolerance in order to prevent cognitive malfunctions
      associated with diabetes. 

PMID- 25851081
TI  - Evaluation of patello-femoral alignment by CT scans: interobserver reliability of
      several parameters.
AB  - Patello-femoral malalignment (PFM) is a common cause of disability often related
      to patello-femoral syndrome (PFS). Several causes have been taken into account; a
      proper diagnosis requires instrumental imaging and a methodical evaluation of
      different parameters. The aim of the present study was to identify the most
      reliable parameters for measuring patello-femoral and inferior limb alignment by
      CT. Twenty randomly selected patients suffering from PFS for a total of 40 knees
      were studied by static CT scans in order to assess patellar tilt, patellar
      displacement, patellar and trochlear morphology and inferior limb alignment. All
      known parameters were measured; the variability of the measurements between
      observers was evaluated by boxplots, Pearson's correlation coefficients, and
      infraclass correlation coefficient [ICC(2,1)] based on a two-way random effect
      model. Bland-Altman mean differences and 95 % limits of agreement were computed
      for each pair of measurements. Patellar tilt parameters appeared equally
      reliable; patellar displacement is best measured with BoTot that showed an ICC of
      0.889; morphology is best measured with WibergTot, with an ICC of 0.862; lastly,
      for the inferior limb alignment parameters' analysis, FTV outperformed the others
      in terms of reliability. The present study allowed us to select a limited number
      of reliable parameters in the evaluation of patello-femoral and inferior limb
      alignment. The use of these parameters may also result in a more reliable
      comparison of studies on PFM and in a better evaluation of the treatment
      outcomes.

PMID- 25851082
TI  - Semantic network mapping of religious material: testing multi-agent computer
      models of social theories against real-world data.
AB  - Agent-based modeling allows researchers to investigate theories of complex social
      phenomena and subsequently use the model to generate new hypotheses that can then
      be compared to real-world data. However, computer modeling has been underutilized
      in regard to the understanding of religious systems, which often require very
      complex theories with multiple interacting variables (Braxton et al. in Method
      Theory Study Relig 24(3):267-290, 2012. doi: 10.1163/157006812X635709 ; Lane in J
      Cogn Sci Relig 1(2):161-180, 2013). This paper presents an example of how
      computer modeling can be used to explore, test, and further understand religious
      systems, specifically looking at one prominent theory of religious ritual. The
      process is continuous: theory building, hypothesis generation, testing against
      real-world data, and improving the model. In this example, the output of an agent
      based model of religious behavior is compared against real-world religious
      sermons and texts using semantic network analysis. It finds that most religious
      materials exhibit unique scale-free small-world properties and that a concept's
      centrality in a religious schema best predicts its frequency of presentation.
      These results reveal that there adjustments need to be made to existing models of
      religious ritual systems and provide parameters for future models. The paper ends
      with a discussion of implications for a new multi-agent model of doctrinal ritual
      behaviors as well as propositions for further interdisciplinary research
      concerning the multi-agent modeling of religious ritual behaviors. 

PMID- 25851084
TI  - Cardiovascular Pathology: From whence we came ... to where we are going.

PMID- 25851083
TI  - Autologous, Noncultured Epidermal Cell Suspension Grafting in the Management of
      Mechanically and Chemically Induced Leukodermic Scars.
AB  - BACKGROUND: Melanocyte-keratinocyte transplant procedure (MKTP) successfully
      repigments postburn leukodermic scars. OBJECTIVE: To further investigate the
      efficacy and limitations of MKTP for treatment of mechanically and chemically
      induced leukodermic scars. METHODS: Ten patients with mechanically or chemically
      induced, depigmented or hypopigmented scars were preoperatively evaluated with
      Wood's light examination, treated with MKTP, and followed for at least 6 months,
      with monitoring of repigmentation and colour matching. RESULTS: Nine patients
      attended at least 6 months of follow-up. Six patients showed no fluorescence of
      scars under Wood's lamp. All patients whose lesions didn't fluoresce displayed
      less than 50% repigmentation, with 5 of 6 attaining 0% to 24%. Of the 3 patients
      displaying bright or some fluorescence, more than 95% repigmentation was achieved
      in 2 patients (skin phototypes V and VI), while less than 24% was attained for
      the third (skin phototype II). CONCLUSIONS: In this small case series, lack of
      fluorescence in leukodermic scars may be a useful negative prognostic indicator
      for MKTP, but additional trials are needed to verify that this is not due to
      melanocompetency.

PMID- 25851086
TI  - Introduction.

PMID- 25851085
TI  - Plexogenic pulmonary hypertension associated with intravenous cocaine abuse.
AB  - Intravenous drug abuse related plexogenic pulmonary hypertension unassociated
      with recurrent thromboembolism or foreign-body granulomatous disease of the lung
      has not been previously reported. Herein, we describe the occurrence of fatal
      plexogenic pulmonary hypertension in a 33-year-old Hispanic woman who had a
      history of chronic intravenous drug abuse. In the absence of other known causes,
      cocaine-induced chronic vasoconstriction was the most probable pathogenic
      mechanism of plexogenic pulmonary hypertension in this patient. 

PMID- 25851087
TI  - Approach to the analysis of cardiac valve prostheses as surgical pathology or
      autopsy specimens.
AB  - Pathologists are likely to encounter substitute heart valves with increasing
      frequency. Informed evaluation of such valves provides valuable information that
      contributes to both patient care and our understanding of the pathobiology of
      host interactions with mechanical devices. This article summarizes the most
      important considerations underlying such analyses-including valve identification,
      common morphologic features and modes of failure, technical details of
      evaluation, and potential pitfalls. 

PMID- 25851088
TI  - Myxomatous mitral valve disease and related entities: The role of matrix in
      valvular heart disease.
AB  - Myxomatous mitral valve disease is a cause of prolapse of mitral valve leaflet(s)
      into the left atrium. In this condition there is a loss of collagen from the
      leaflet and an accumulation of glycosaminoglycan. Complications of myxomatous
      mitral valve disease include infective endocarditis, mitral regurgitation, sudden
      death, and stroke. Mitral valve prolapse has been reported to occur in
      association with many syndromes. In some of these, such as Marfan syndrome, the
      pathology of the mitral valve has been well described and is that of a myxomatous
      valve. However, in some of the other disorders associated with mitral valve
      prolapse, there is no information yet available on the valve pathology, and this
      would be useful in order to better understand the pathogenesis of myxomatous
      mitral valve disease. 

PMID- 25851089
TI  - Update on pathogenesis of infective endocarditis.
AB  - Specific interactions between pathogens and host factors contribute to the
      apparent tissue and microbial selectivity in infective endocarditis. Streptococci
      and staphylococci can produce exopolysaccharides and peptides that have been
      implicated in adherence to host factors. The presence of a platelet-fibrin matrix
      on the surface of endothelium can serve as a nidus for colonization by gram
      positive cocci, which in turn can promote further aggregation of platelets.
      Tissue factor expression by valvular endothelial cells is low but can be turned
      on by endocytosis of staphylococci-this could favor infected thrombus formation.
      The presence of a foreign body such as a prosthetic heart valve increases the
      risk of endocarditis. Platelets can promote adherence of staphylococci to foreign
      body surfaces. Infection of heart valves is the result of influences that in the
      end will favor microbial attachment and survival. Normal endothelium is resistant
      to colonization by microorganisms. Antibodies and phagocytes offer some
      protection against the development of endocarditis. Platelets produce
      microbicidal proteins that appear important in containing the infection. New
      diagnostic criteria for endocarditis take into account the pathogenetic
      characteristics of the disease. 

PMID- 25851090
TI  - Complications of cardiac valve surgery and their autopsy investigation.
AB  - This review describes the broad spectrum of complications that may attend cardiac
      valve replacement surgery. Patient morbidity and mortality may be a consequence
      of preoperative condition or care, operative complications, or postoperative
      course. Careful autopsy examination of patient deaths, correlated with clinical
      information, will usually reveal an explanation for a patient's demise, as well
      as precipitating or contributing factors. The autopsy is particularly valuable if
      it can demonstrate technical, prosthetic, or other unexpected findings whose
      communication to clinicians and manufacturers can serve to improve the care of
      subsequent patients, or the development of improved prostheses. 

PMID- 25851091
TI  - New concepts in the design and use of biological prosthetic valves.
AB  - The natural aortic valve is a structure that has thus far eluded all attempts at
      duplication with synthetic materials. Real success in the replacement of the
      aortic valve has come about primarily through the use of biological devices, such
      as the porcine aortic valve xenograft. In the future, bioprostheses based more
      closely on the natural aortic valve may ultimately succeed where synthetic
      approaches have failed. Some recent advances in the design and development of
      bioprosthetic heart valves, such as the absence of a stent and the better
      preservation of the valve's natural biomechanical properties, show considerable
      promise in improving the long term durability of these devices. With a greater
      understanding of the structure/function relationship of the aortic valve at the
      micromechanical level, the future of bioprostheses may be even more biologically
      oriented than it is today. 

PMID- 25851092
TI  - Ebstein's malformation.

PMID- 25851093
TI  - Ebstein's malformation.

PMID- 25851094
TI  - Images in Anesthesiology: Spontaneous Hyphema after Cardiac Surgery.

PMID- 25851095
TI  - Is there a place for nutrition-sensitive agriculture?
AB  - The focus of the review paper is to discuss how biotechnological innovations are
      opening new frontiers to mitigate nutrition in key agricultural crops with
      potential for large-scale health impact to people in Africa. The general
      objective of the Africa Biofortified Sorghum (ABS) project is to develop and
      deploy sorghum with enhanced pro-vitamin A to farmers and end-users in Africa to
      alleviate vitamin A-related micronutrient deficiency diseases. To achieve this
      objective the project technology development team has developed several promising
      high pro-vitamin A sorghum events. ABS 203 events are so far the most advanced
      and well-characterised lead events with about 12 MUg beta-carotene/g tissue which
      would supply about 40-50 % of the daily recommended vitamin A at harvest. Through
      gene expression optimisation other events with higher amounts of pro-vitamin A,
      including ABS 214, ABS 235, ABS 239 with 25, 30-40, 40-50 MUg beta-carotene/g
      tissue, respectively, have been developed. ABS 239 would provide twice
      recommended pro-vitamin A at harvest, 50-90 % after 3 months storage and 13-45 %
      after 6 months storage for children. Preliminary results of introgression of ABS
      pro-vitamin A traits into local sorghum varieties in target countries Nigeria and
      Kenya show stable introgression of ABS vitamin A into local farmer-preferred
      sorghums varieties. ABS gene Intellectual Property Rights and Freedom to Operate
      have been donated for use royalty free for Africa. Prior to the focus on the
      current target countries, the project was implemented by fourteen institutions in
      Africa and the USA. For the next 5 years, the project will complete ABS product
      development, complete regulatory science data package and apply for product
      deregulation in target African countries. 

PMID- 25851096
TI  - Rio1 promotes rDNA stability and downregulates RNA polymerase I to ensure rDNA
      segregation.
AB  - The conserved protein kinase Rio1 localizes to the cytoplasm and nucleus of
      eukaryotic cells. While the roles of Rio1 in the cytoplasm are well
      characterized, its nuclear function remains unknown. Here we show that nuclear
      Rio1 promotes rDNA array stability and segregation in Saccharomyces cerevisiae.
      During rDNA replication in S phase, Rio1 downregulates RNA polymerase I (PolI)
      and recruits the histone deacetylase Sir2. Both interventions ensure rDNA copy
      number homeostasis and prevent the formation of extrachromosomal rDNA circles,
      which are linked to accelerated ageing in yeast. During anaphase, Rio1
      downregulates PolI by targeting its subunit Rpa43, causing PolI to dissociate
      from the rDNA. By stimulating the processing of PolI-generated transcripts at the
      rDNA, Rio1 allows for rDNA condensation and segregation in late anaphase. These
      events finalize the genome transmission process. We identify Rio1 as an essential
      nucleolar housekeeper that integrates rDNA replication and segregation with
      ribosome biogenesis. 

PMID- 25851097
TI  - A pyrosequencing insight into sprawling bacterial diversity and community
      dynamics in decaying deadwood logs of Fagus sylvatica and Picea abies.
AB  - Deadwood is an important biodiversity hotspot in forest ecosystems. While
      saproxylic insects and wood-inhabiting fungi have been studied extensively,
      little is known about deadwood-inhabiting bacteria. The study we present is among
      the first to compare bacterial diversity and community structure of deadwood
      under field conditions. We therefore compared deadwood logs of two temperate
      forest tree species Fagus sylvatica and Picea abies using 16S rDNA pyrosequencing
      to identify changes in bacterial diversity and community structure at different
      stages of decay in forest plots under different management regimes.
      Alphaproteobacteria, Acidobacteria and Actinobacteria were the dominant taxonomic
      groups in both tree species. There were no differences in bacterial OTU richness
      between deadwood of Fagus sylvatica and Picea abies. Bacteria from the order
      Rhizobiales became more abundant during the intermediate and advanced stages of
      decay, accounting for up to 25% of the entire bacterial community in such logs.
      The most dominant OTU was taxonomically assigned to the genus Methylovirgula,
      which was recently described in a woodblock experiment of Fagus sylvatica.
      Besides tree species we were able to demonstrate that deadwood physico-chemical
      properties, in particular remaining mass, relative wood moisture, pH, and C/N
      ratio serve as drivers of community composition of deadwood-inhabiting bacteria. 

PMID- 25851099
TI  - Safinamide: first global approval.
AB  - Safinamide (Xadago((r))) is an oral alpha-aminoamide derivative developed by
      Newron for the treatment of Parkinson's disease (PD). The drug has both
      dopaminergic properties (highly selective and reversible inhibition of monoamine
      oxidase-B) and non-dopaminergic properties (selective sodium channel blockade and
      calcium channel modulation, with consequent inhibition of excessive glutamate
      release). Safinamide is approved in the EU, Iceland, Lichtenstein and Norway, as
      an add-on therapy to stable-dose levodopa, alone or in combination with other PD
      therapies in mid- to late-stage fluctuating PD patients; regulatory submissions
      have also been filed in the USA and Switzerland for its use in this indication.
      Additional submissions have been made in the USA, Iceland, Lichtenstein, Norway
      and Switzerland for early-stage PD. Safinamide has also undergone phase II
      investigation in PD patients with drug-induced dyskinesia (France, Germany,
      Austria, Canada and South Africa) or cognitive impairment (USA and Spain). This
      article summarizes the milestones in the development of safinamide leading to its
      first approval for PD. 

PMID- 25851098
TI  - Depression in type 2 diabetes mellitus: prevalence, impact, and treatment.
AB  - Clinically significant depression is present in one of every four people with
      type 2 diabetes mellitus (T2DM). Depression increases the risk of the development
      of T2DM and the subsequent risks of hyperglycemia, insulin resistance, and micro-
      and macrovascular complications. Conversely, a diagnosis of T2DM increases the
      risk of incident depression and can contribute to a more severe course of
      depression. This linkage reflects a shared etiology consisting of complex
      bidirectional interactions among multiple variables, a process that may include
      autonomic and neurohormonal dysregulation, weight gain, inflammation, and
      hippocampal structural alterations. Two recent meta-analyses of randomized
      controlled depression treatment trials in patients with T2DM concluded that
      psychotherapy and antidepressant medication (ADM) were each moderately effective
      for depression and that cognitive behavior therapy (CBT) had beneficial effects
      on glycemic control. However, the number of studies (and patients exposed to
      randomized treatment) included in these analyses is extremely small and limits
      the certainty of conclusions that can be drawn from the data. Ultimately, there
      is no escaping the paucity of the evidence base and the need for additional
      controlled trials that specifically address depression management in T2DM. Future
      trials should determine both the effects of treatment and the change in
      depression during treatment on measures of mood, glycemic control, and medical
      outcome. 

PMID- 25851100
TI  - Foreword: all things considered about probiotics, prebiotics and intestinal
      microbiota in children - from bench to bedside.
AB  - There are numerorus published and ongoing experimental/clinical studies about
      probiotics and prebiotics, intestinal microbiota and nutrition. Three years ago,
      at the first International Symposium of Probiotics Prebiotics in Paediatrics in
      Istanbul (2012) we highlighted the 'paediatric perspective' on these issues and
      brought together more than 40 global key opinion leaders and 400 attendants to
      have a chance to extensively discuss the past, present and the future. In 2014,
      the second state of art congress, held in Antalya, aimed to discuss the gut
      microbiota and microbiotics and their impact through lifespan. Selected papers of
      this conference are presented in this special issue 'prebiotics and probiotics in
      paediatrics' of Beneficial Microbes. A summary of the conference results is
      provided below.

PMID- 25851101
TI  - Bugs for atopy: the Lactobacillus rhamnosus GG strategy for food allergy
      prevention and treatment in children.
AB  - Food allergy (FA) is a major health issue for children living in Western
      countries. At this time the only proven treatment for FA is elimination of
      offender antigen from the diet. It is becoming clear that the development of gut
      microbiota exerts a profound influence on immune system maturation and tolerance
      acquisition. Increasing evidence suggests that perturbations in gut microbiota
      composition of infants are implicated in the pathogenesis of FA. These findings
      have unveiled new strategies to prevent and treat FA using probiotics bacteria or
      bacterial substance to limit T-helper (Th)/Th2 bias, which changes during the
      disease course. Selected probiotics administered during infancy may have a role
      in the prevention and treatment of FA. Lactobacillus rhamnosus GG (LGG) is the
      most studied probiotic in this field. Administration of LGG in early life have a
      role in FA prevention. Preliminary evidence shows that LGG accelerates oral
      tolerance acquisition in cow's milk allergic infants. We are understanding the
      mechanisms elicited by LGG and metabolites in influencing food allergen
      sensitization. A deeper definition of these mechanisms is opening the way to new
      immunotherapeutics for children affected by FA that can efficiently limit the
      disease burden. 

PMID- 25851104
TI  - Addition of ethylene to a pi-conjugated two-dimensional nickel-based
      organometallic framework with implications for olefin separation.
AB  - We have investigated the mechanism for the reversible addition of ethylene to a
      periodic 2D network of square-planar nickel centers ([Ni(SC)4]n) using density
      functional theory. The mechanism is analogous to that for homogeneous olefin
      binding to metal bis(dithiolene) complexes. We considered periodic boundary
      calculations (PBC) as well as clusters containing up to 12 nickel atoms using a
      screened hybrid density functional to obtain accurate reaction barriers. Several
      different products were analyzed. The lowest-energy route begins with the
      addition of ethylene across the nickel-sulfur bond, which has previously not been
      considered for this system. The effect of the addition of several alkene
      molecules simultaneously on the surface was investigated to determine the
      potential efficiency of this material. This material is a candidate for alkene
      purification as it exhibits similar reactivity to its molecular analog in terms
      of the relative stability of products, energy barriers, and molecular efficiency
      while also providing the intrinsic technical benefits of heterogeneous catalysis.

PMID- 25851102
TI  - The impact of lifestyle intervention on sedentary time in individuals at high
      risk of diabetes.
AB  - AIMS/HYPOTHESIS: The Diabetes Prevention Program (DPP) lifestyle intervention
      successfully achieved its goal of increasing leisure physical activity levels.
      This current study examines whether the lifestyle intervention also changed time
      spent being sedentary and the impact of sedentary time on diabetes development in
      this cohort. METHODS: 3,232 DPP participants provided baseline data. Sedentary
      behaviour was assessed via an interviewer-administered questionnaire and reported
      as time spent watching television specifically (or combined with sitting at
      work). Mean change in sedentary time was examined using repeated measures ANCOVA.
      The relationship between sedentary time and diabetes incidence was determined
      using Cox proportional hazards models. RESULTS: During the DPP follow-up (mean:
      3.2 years), sedentary time declined more in the lifestyle than the metformin or
      placebo participants (p < 0.05). For the lifestyle group, the decrease in
      reported mean television watching time (22 [95% CI 26, 17] min/day) was greater
      than in the metformin or placebo groups (p < 0.001). Combining all participants
      together, there was a significantly increased risk of developing diabetes with
      increased television watching (3.4% per hour spent watching television), after
      controlling for age, sex, treatment arm and leisure physical activity (p < 0.01),
      which was attenuated when time-dependent weight was added to the model.
      CONCLUSIONS/INTERPRETATION: In the DPP, the lifestyle intervention was effective
      at reducing sedentary time, which was not a primary goal. In addition, in all
      treatment arms, individuals with lower levels of sedentary time had a lower risk
      of developing diabetes. Future lifestyle intervention programmes should emphasise
      reducing television watching and other sedentary behaviours in addition to
      increasing physical activity. TRIAL REGISTRATION: ClinicalTrials.gov NCT00004992.

PMID- 25851103
TI  - Clinical management and humoral immune responses to rabies post-exposure
      prophylaxis among three patients who received solid organs from a donor with
      rabies.
AB  - BACKGROUND: The rabies virus causes a fatal encephalitis and can be transmitted
      through organ transplantation. In 2013, a man developed rabies 18 months after
      receiving a kidney from a donor with rabies, who was not known to have been
      infected when the organs were procured. Three additional persons who received
      organs from the same donor (liver, kidney, heart), all of whom were not
      vaccinated for rabies before transplantation, received rabies post-exposure
      prophylaxis (PEP) with rabies immune globulin and 5 doses of rabies vaccine as
      soon as the diagnosis of rabies was made in the donor (18 months after their
      transplant surgeries). We describe their clinical management. METHODS: As the 3
      recipients were all on immunosuppressive medications, post-vaccination serologic
      testing was performed using the rapid fluorescent focus inhibition test to
      measure rabies virus neutralizing antibodies (RVNAs). An acceptable antibody
      response to administration of rabies vaccine was defined as detection of RVNAs at
      a concentration >=0.1 IU/mL from a serum specimen collected >=7 days after the
      fifth vaccine dose. RESULTS: All 3 recipients demonstrated an acceptable antibody
      response despite their immunosuppressed states. More than 36 months have passed
      since their transplant surgeries, and all 3 recipients have no evidence of
      rabies. CONCLUSIONS: The survival of 3 previously unvaccinated recipients of
      solid organs from a donor with rabies is unexpected. Although the precise factors
      that led to their survival remain unclear, our data suggest that PEP can possibly
      enhance transplant safety in settings in which donors are retrospectively
      diagnosed with rabies.

PMID- 25851105
TI  - On the interactions of leflunomide and teriflunomide within receptor cavity--NMR
      studies and energy calculations.
AB  - Leflunomide is a disease-modifying antirheumatic drug with antiinflammatory and
      immunosuppressive activity used for the treatment of psoriatic and rheumatoid
      arthritis. It undergoes rapid metabolization to teriflunomide, a metabolite that
      is responsible for the biological activity of leflunomide. Continuing our
      investigations on the interactions of biologically important azahetarenes with
      the environment, we focused on leflunomide and its active metabolite,
      teriflunomide, considering the interactions teriflunomide-amino acid within the
      target protein (dihydroorotate dehydrogenase) using density functional theory, as
      well as ONIOM techniques. The results of theoretical studies have shown that the
      interactions of teriflunomide with tyrosine and arginine involve principally the
      amide fragment of teriflunomide. The presence of the internal hydrogen bond
      between (Z)-teriflunomide carbonyl oxygen and enolic hydroxyl decreases the
      interaction strength between teriflunomide and tyrosine or arginine. Even the E
      isomer of teriflunomide would usually provide a stronger interaction
      teriflunomide-amino acid than the Z isomer with the internal hydrogen bond. 

PMID- 25851106
TI  - Theoretical study of spectroscopic constants and anharmonic force field of SiF2.
AB  - The equilibrium structure, spectroscopy constants, and anharmonic force field of
      SiF2 have been investigated at MP2, B3LYP, and B3PW91 levels of theory employing
      two basis sets cc-pVQZ and cc-pVTZ, respectively. The obtained equilibrium
      geometries, rotational constants, fundamental vibrational wave numbers, and
      centrifugal distortion constants are compared with the available experimental
      data or the previous theoretical values. The MP2/cc-pVQZ results of SiF2 are in
      excellent agreement with the available experimental data and afford a marked
      improvement over B3LYP/cc-pVQZ and B3PW91/cc-pVQZ in the calculation of
      spectroscopic constants and force constants of SiF2. The basis set enhancement
      beyond cc-pVQZ does not lead to a major improvement so that the cc-pVQZ basis set
      is sufficient for SiF2. The MP2/cc-pVQZ results may provide useful data for the
      spectroscopic experiment studies of SiF2. The used DFT method is also an
      advisable choice to study anharmonic force field of SiF2. 

PMID- 25851107
TI  - Understanding the role of the trifluoromethyl group in reactivity and
      regioselectivity in [3+2] cycloaddition reactions of enol acetates with nitrones.
      A DFT study.
AB  - The mechanism of the [3+2] cycloaddition (32CA) reaction of C-phenyl-N
      methylnitrone with ethyl trifluoroacetoacetate has been theoretically studied at
      the MPWB1K/6-311G(d,p) level. This 32CA reaction, in which the enol form of the
      beta-keto ester participates as the ethylene component, takes place with complete
      ortho regioselectivity and exo stereoselectivity. The presence of the CF3 group
      in the beta-position in the enol acetate accelerates the 32CA reaction, but it
      does not modify the regioselectivity, which is controlled by the presence of the
      ester group. While ortho regioselectivity is reproduced by the MPWB1K
      calculations, the endo selectivity is not. The inclusion of solvent effects
      slightly decreases the reactivity but does not modify the gas phase
      selectivities. Analysis of the DFT global reactivity indices and the Parr
      functions in reagents provide a rationalization for the participation of ethyl
      trifluoroacetoacetate and the regioselectivity in this zw-type 32CA reaction. 

PMID- 25851108
TI  - A theoretical study of the unfolding pathway of reduced human serum albumin.
AB  - The unfolding of the reduced human serum albumin (HSA) was simulated by
      generating four molecular dynamics (MD) trajectories of 160 ns each at 350, 375,
      400, and 425 K, respectively. A principal components analysis (PCA) was performed
      on the four trajectories. Based on this analysis, 17 representative protein
      conformers were identified and subsequently used to construct a sequence of
      partially unfolded structures. They were ordered according to their decreasing
      alpha-helix fractions. The structural evolution in this unfolding sequence was
      found to be continuous at global but also at local level supporting the
      hypothesis that the protein unfolding pathway is not significantly dependent on
      the simulation temperature. As a result, the alpha-helix fraction of the protein
      appears to be a good reaction coordinate for the unfolding process, as it was
      previously suggested by experiments. Based on this observation, two conformers in
      the unfolding sequence were predicted to be close to the equilibrium structure of
      reduced HSA thus providing a first theoretical model for this protein form. 

PMID- 25851109
TI  - Accuracy of 3D dual echo steady state (DESS) MR arthrography to quantify
      acetabular cartilage thickness.
AB  - PURPOSE: To deploy and quantify the accuracy of 3D dual echo steady state (DESS)
      MR arthrography with hip traction to image acetabular cartilage. Clinical
      magnetic resonance imaging (MRI) sequences used to image hip cartilage often have
      reduced out-of-plane resolution and may lack adequate signal-to-noise to image
      cartilage. MATERIALS AND METHODS: Saline was injected into four cadaver hips
      placed under traction. 3D DESS MRI scans were obtained before and after cores of
      cartilage were harvested from the acetabulum; the two MRIs were spatially aligned
      to reference core positions. The thickness of cartilage cores was measured under
      microscopy to serve as the reference standard. 3D reconstructions of cartilage
      and subchondral bone were generated using automatic and semiautomatic image
      segmentation. Cartilage thickness estimated from the 3D reconstructions was
      compared to physical measurements using Bland-Altman plots. RESULTS: As revealed
      by the automatic segmentation mask, saline imbibed the joint space throughout the
      articulating surface, with the exception of the posteroinferior region in two
      hips. Locations where air bubbles were introduced and regions of suspected low
      density bone disrupted an otherwise smooth automatic segmentation mask. Automatic
      and semiautomatic segmentation yielded a bias +/- repeatability coefficient (95%
      limits of agreement) of 0.10 +/- 0.51 mm (-0.41 to 0.61 mm) and 0.06 +/- 0.43 mm
      (-0.37 to 0.49 mm), respectively. CONCLUSION: Cartilage thickness can be
      estimated to within ~0.5 mm of the physical value with 95% confidence using 3D
      reconstructions of 3D DESS MR arthrography images. Manual correction of the
      automatic segmentation mask may improve reconstruction accuracy.

PMID- 25851110
TI  - Resveratrol reduces amyloid-beta (Abeta1-42)-induced paralysis through targeting
      proteostasis in an Alzheimer model of Caenorhabditis elegans.
AB  - PURPOSE: Resveratrol is a polyphenol present in red wine for which the capability
      of directly interfering with the hallmark of Alzheimer's disease (AD), i.e. toxic
      beta-amyloid protein (Abeta) aggregation, has been shown recently. Since the
      stimulation of proteostasis could explain reduced Abeta-aggregation, we searched
      for proteostasis targets of resveratrol. METHODS: The transgenic Caenorhabditis
      elegans strain CL2006, expressing Abeta1-42 under control of a muscle-specific
      promoter and responding to Abeta-toxicity with paralysis, was used as a model.
      Target identification was accomplished through specific knockdowns of
      proteostasis genes by RNA interference. Effects of resveratrol on protein
      aggregation were identified using ProteoStat((r)) Detection Reagent, and
      activation of proteasomal degradation by resveratrol was finally proven using a
      specific fluorogenic peptide substrate. RESULTS: Resveratrol at a concentration
      of 100 uM caused a 40 % decrease in paralysis. UBL-5 involved in unfolded protein
      response (UPR) in mitochondria proved to be necessary for the prevention of Abeta
      toxicity by resveratrol. Also XBP-1, which represents an endoplasmic reticulum
      resident factor involved in UPR, was identified to be necessary for the effects
      of resveratrol. Regarding protein degradation pathways, the inhibition of
      macroautophagy and chaperone-mediated autophagy prevented resveratrol from
      reducing paralysis as did the inhibition of proteasomal degradation. Finally,
      resveratrol reduced the amount of lysosomes, suggesting increased flux of
      proteins through the autophagy pathways and activated proteasomal degradation.
      CONCLUSIONS: Resveratrol reduces the Abeta-induced toxicity in a C. elegans model
      of AD by targeting specific proteins involved in proteostasis and thereby reduces
      the amount of aggregated Abeta.

PMID- 25851112
TI  - Erratum to: Modified technique of levator plication for the correction of Marcus
      Gunn jaw-winking ptosis: a case series.

PMID- 25851111
TI  - Overlap between linear scleroderma, progressive facial hemiatrophy and immune
      inflammatory encephalitis in a paediatric cohort.
AB  - Linear scleroderma en coup the sabre (LSCS), progressive facial hemiatrophy (PFH)
      and autoimmune encephalitis are distinct clinical entities, although patients
      with overlapping features have been reported. We performed a multicenter
      retrospective review of a series of children with LSCS and/or PFH to explore the
      relation between these entities. The files of 16 children were reviewed, 11
      presented with LSCS, 5 with PFH, with time overlapping cutaneous features were
      seen. Extracutaneous signs were found in both groups. ANA were present in more
      than 50 % of patients. Almost half of our patients presented with CNS
      manifestations comprising unilateral headache, migraine and epilepsy with or
      without abnormalities on MRI. Brain biopsy in one patient was consistent with
      Rasmussen encephalitis. In two other children, associated autoimmune
      manifestations were present. CONCLUSION: Our patient cohort brings more arguments
      to consider LSCS and PFH as a single disease entity with LSCS and superficial
      skin involvement at one end of the spectrum and PFH with involvement of
      subcutaneous deep tissue at the other end. In both entities, encephalitis can be
      observed. Our findings of circulating ANA, intradermal lymphocytes and IgG,
      intrathecal IgG production and clinical improvement with immunosuppressive
      therapy endorse the concept of a possible common immune-inflammatory
      pathogenesis. WHAT IS KNOWN: * LSCS, PFH and immune-inflammatory encephalitis are
      distinct clinical entities, but patients with overlapping features have been
      reported. WHAT IS NEW: * We present a unique paediatric cohort with LSCS, PFH
      and/or encephalitis. * We endorse the concept of a common immune-inflammatory
      disease process.

PMID- 25851113
TI  - Label-free quartz crystal microbalance with dissipation monitoring of resveratrol
      effect on mechanical changes and folate receptor expression levels of living MCF
      7 cells: a model for screening of drugs.
AB  - Quartz crystal microbalance with dissipation (QCM-D) monitoring was used for real
      time and label-free detection of changes and folate receptor (FR) expression
      levels on living MCF-7 cells for evaluating the anticancer activity of
      resveratrol. Here, the mechanical changes of cellular responses to resveratrol
      were tracked by a poly(l-lysine) (PLL) modified QCM-D sensor, and the inhibition
      effect of resveratrol on FR expression levels on MCF-7 cells was monitored by
      chitosan-folic acid (CS-FA) composite membrane functionalized Au substrate for
      the first time. Changes in morphology and the cellular state of MCF-7 cells
      stimulated by resveratrol at different concentrations were detected by inverted
      fluorescence microscopy and flow cytometry. Atomic force microscopy confirmed
      that resveratrol influenced the cellular mechanical properties. The results
      indicated that the MCF-7 cells lose their original elasticity and increase their
      stiffness induced by resveratrol. It was further observed by confocal
      fluorescence imaging that resveratrol reduced the FR expression levels on the
      living cells surface. This study established a typical model of the QCM-D
      biosensor to evaluate the protein biomarker expression levels on the cells
      surface. QCM-D, which was used to investigate potential targets for an antitumor
      drug on living cells and realize a better understanding of the drug action
      mechanism, was expected to be developed into a promising tool for the screening
      of drugs. 

PMID- 25851114
TI  - Diagnostic yield of echocardiography in cancer patients with ischemic stroke.
AB  - The yield of echocardiography in cancer patients with acute ischemic stroke is
      unknown. We identified adult patients with active systemic cancer diagnosed with
      acute ischemic stroke at a tertiary-care cancer center from 2005 through 2009 who
      underwent transthoracic (TTE) or transesophageal echocardiography (TEE). Two
      neurologists independently reviewed all clinical data, including TTE and TEE
      reports, and adjudicated whether echocardiographic studies revealed a definite or
      possible source of stroke according to pre-defined criteria. Patients were
      classified as having suspected cardioembolic strokes if imaging showed embolic
      appearing infarcts in more than one vascular territory. Among 220 patients with
      cancer and ischemic stroke who underwent echocardiography, 216 (98%) had TTE and
      37 (17%) had TEE. TTE revealed a definite source in 15 (7%, 95% CI 4-10%)
      patients and a possible source in 42 (19%, 95% CI 14-25%), while TEE revealed a
      definite source in 10 (27%, 95% CI 12-42%) patients and a possible source in 14
      (38%, 95% CI 21-54%). In 92 patients with suspected cardioembolic strokes who
      underwent TTE, 6 (7%, 95% CI 1-12%) had a definite source, including 4 with
      marantic endocarditis, and 20 (22%, 95% CI 13-30%) had a possible source. Twenty
      one of these patients also underwent TEE, which demonstrated a definite or
      possible source in 16 (76%, 95% CI 56-96%) patients, including marantic
      endocarditis in 4 (19%). The yield of TTE for detecting marantic endocarditis and
      other cardiac sources of stroke in cancer patients is low, but TEE may provide a
      higher yield in targeted patients.

PMID- 25851115
TI  - Development and psychometric evaluation of patient needs assessment in palliative
      care (PNAP) instrument.
AB  - OBJECTIVE: Although assessment of palliative patients' needs is a key issue in
      palliative care, a suitable instrument for identification of such needs is not
      available in Central European countries. Our objectives were to produce an
      adequate tool for identifying the importance and satisfaction of palliative
      patients' needs and to verify its psychometric properties. METHOD: The patient
      needs assessment in palliative care (PNAP) instrument was constructed based on a
      literature review and qualitative research (focus groups, n = 5). The
      psychometric properties of the questionnaire were verified by a cross-sectional
      study. The convergent validity of the questionnaire was determined by
      confirmatory factor analysis. Furthermore, internal consistency, test-retest
      reliability, and construct validity were also tested. The qualitative research
      group comprised 30 participants (27 experts in palliative care, 1 patient, and 2
      family members). Psychometric properties were evaluated in a group of 349
      hospital inpatients terminally ill with chronic disease or cancer and receiving
      palliative care. RESULTS: Based on the qualitative data analysis, a questionnaire
      was constructed that contained 42 items grouped into 5 domains. When testing the
      psychometric properties of the questionnaire, a new model containing 40 items in
      7 domains was produced. Cronbach's alpha for the entire PNAP questionnaire was
      0.89 on the importance scale and 0.80 on the satisfaction scale. Test-retest
      reliability was higher than 0.7 for all domains in both scales. SIGNIFICANCE OF
      RESULTS: The results of tests on the psychometric properties of the PNAP
      questionnaire showed at least satisfactory validity and reliability, and it can
      be employed to assess the needs of palliative care patients in Central European
      countries.

PMID- 25851116
TI  - Why should governments invest in antibiotic drug discovery against multi-drug
      resistant bacteria?

PMID- 25851117
TI  - Crofelemer: In HIV Associated Diarrhea and Secretory Diarrhea - A Patent
      Perspective.
AB  - PURPOSE: Diarrhea and dehydration caused by enteric infections is a major factor
      of morbidity and mortality worldwide. Secretory diarrhea can be devastating
      especially among infants, children, and HIV infected people and can result in
      death of more than 50% of its victims for without adequate rehydration, patients
      are at maximum risk during the first 6-18 hours. Hence, it is a leading cause of
      morbidity and mortality worldwide. Diarrhea is experienced by over 50% of AIDS
      patients at some time or other during the course of their illness, which is an
      important cause of increased morbidity and mortality in them. Currently, the
      standard-of-care therapy focuses only on rehydration therapy to combat
      dehydration and antibiotic therapy that targets the infectious agent only.
      Though, antimicrobial drugs have been the key treatment for diarrhea but, with
      the emergence of resistant strains the search for novel targets/drugs is on, for
      diarrhea still continues to kill millions. METHODS: A literature search was done
      using secretory diarrhea and Crofelemer, as key words using PubMed (Medline),
      ProQuest, Cochrane Library, Medscape and Google Scholar search engines from
      January 2012 to December 2014. The types of articles included in this review were
      original research, review papers, recent patents and editorials from various
      medical schools across the globe. Though, it was practically not possible to
      include all studies, one can marvel at all the proclaimed mechanism of action of
      Crofelemer in this study. RESULTS: Crofelemer, a channel blocker of intestinal
      chloride channels such as the Cystic Fibrosis Transmembrane Conductance Regulator
      (CFTR) and the Calcium Activated Chloride Channels (CaCCs) plays significant
      roles in providing symptomatic relief in secretory diarrhea. CONCLUSION:
      Crofelemer is a first-in-class agent that possesses a unique mechanism of action
      through dual inhibition of both the intestinal chloride channels in secretory
      diarrhea.

PMID- 25851118
TI  - Making meaning of pumping for mothers of infants with congenital diaphragmatic
      hernia.
AB  - OBJECTIVE: To describe the process of initiation and maintenance of milk supply
      and potential transition to direct breastfeeding among mother/infant dyads with
      infants with congenital diaphragmatic hernia (CDH). SETTING: A Level-III neonatal
      intensive care unit. PARTICIPANTS: Eleven mother/infant dyads with infants with
      CDH. METHODS: Prospective, longitudinal qualitative descriptive design.
      Semistructured interviews were conducted over the course of the NICU stay.
      Conventional content analysis was used. RESULTS: Human milk oral care emerged
      from the interview data as a strong facilitating factor to encouraging mothers to
      continue pumping during hospitalization. Four main themes emerged regarding the
      importance and value of human milk oral care for the mothers in relation to
      pumping and maintenance of milk supply: (a) It motivates me; (b) I'm a part of my
      baby getting better; (c) We do it together, and (d) We're getting somewhere.
      CONCLUSIONS: The findings of this study reflect the importance and value of human
      milk oral care as a driving factor to motivate mothers to maintain milk supply
      during the critical time when the infant with CDH is not able to take in enteral
      nutrition and throughout the hospital stay.

PMID- 25851119
TI  - Pharmacokinetics of minocycline in domestic cats.
AB  - OBJECTIVES: Recently, the increased cost and decreased availability of
      doxycycline has sparked an interest in using minocycline as an alternative. The
      purpose of this study was to determine the pharmacokinetics of minocycline in
      domestic cats in order to facilitate dosage decisions. METHODS: Purpose-bred,
      young adult cats were administered a single dose of either intravenous (IV; n =
      4; 5 mg/kg) or oral (n = 6; 50 mg/cat) minocycline. Blood was collected from each
      at intervals up to 24 h afterwards. Minocycline was measured using high
      performance liquid chromatography with ultraviolet detection. A one-compartment
      pharmacokinetic model was fit to the oral data and a two-compartment model to the
      IV data via a computer program. Plasma protein binding was measured by fortifying
      blank plasma from untreated healthy cats with minocycline at two concentrations
      and applying an ultracentrifugation method. RESULTS: Two cats became transiently
      lethargic and tachypneic during IV drug infusion. One cat vomited 6.0 h after
      infusion, and two cats vomited either 1.5 h or ~5.0 h after oral drug
      administration. The mean oral dose administered was 13.9 +/- 0.47 mg/kg. Oral
      bioavailability was approximately 62%. Plasma protein binding was 60% at 5 ug/ml
      and 46% at 1 MUg/ml. After IV administration, elimination half-life (t(1/2)),
      apparent volume of distribution at steady-state, and systemic clearance were 6.7
      h (coefficient of variation [CV] 14.4%), 1.5 l/kg (CV 34.5%) and 2.9 ml/kg/min
      (CV 40.8%), respectively. After oral administration the terminal t(1/2) and peak
      concentration (Cmax) were 6.3 h (CV 9%) and 4.77 ug/ml (CV 36%), respectively.
      CONCLUSIONS AND RELEVANCE: Because most bacteria will have a minimum inhibitory
      concentration of ?0.5 MUg/ml, an oral dose of 8.8 mg/kg q24h would be adequate to
      meet pharmacokinetic-pharmacodynamic targets after adjusting for protein binding.
      Although some gastrointestinal upset may occur, one 50 mg capsule orally q24h
      would provide appropriate dosing for most cats.

PMID- 25851120
TI  - Degradable hydrogels derived from PEG-diacrylamide for hepatic tissue
      engineering.
AB  - Engineered tissue constructs have the potential to augment or replace whole organ
      transplantation for the treatment of liver failure. Poly(ethylene glycol) (PEG)
      based systems are particularly promising for the construction of engineered liver
      tissue due to their biocompatibility and amenability to modular addition of
      bioactive factors. To date, primary hepatocytes have been successfully
      encapsulated in non-degradable hydrogels based on PEG-diacrylate (PEGDA). In this
      study, we describe a hydrogel system based on PEG-diacrylamide (PEGDAAm)
      containing matrix-metalloproteinase sensitive (MMP-sensitive) peptide in the
      hydrogel backbone that is suitable for hepatocyte culture both in vitro and after
      implantation. By replacing hydrolytically unstable esters in PEGDA with amides in
      PEGDAAm, resultant hydrogels resisted non-specific hydrolysis, while still
      allowing for MMP-mediated hydrogel degradation. Optimization of polymerization
      conditions, hepatocellular density, and multicellular tissue composition
      modulated both the magnitude and longevity of hepatic function in vitro.
      Importantly, hepatic PEGDAAm-based tissues survived and functioned for over 3
      weeks after implantation ectopically in the intraperitoneal (IP) space of nude
      mice. Together, these studies suggest that MMP-sensitive PEGDAAm-based hydrogels
      may be a useful material system for applications in tissue engineering and
      regenerative medicine. (c) 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part
      A: 103A: 3331-3338, 2015. 

PMID- 25851122
TI  - Recurrent venous thromboembolism in anticoagulated patients with cancer:
      management and short-term prognosis.
AB  - BACKGROUND: Recommendations for management of cancer-related venous
      thromboembolism (VTE) in patients already receiving anticoagulant therapy are
      based on low-quality evidence. This international registry sought to provide more
      information on outcomes after a breakthrough VTE in relation to anticoagulation
      strategies. METHODS: Patients with cancer and VTE despite anticoagulant therapy
      were reported to the registry. Data on treatments, VTE events, major bleeding,
      residual thrombosis symptoms and death were collected for the following 3 months.
      Breakthrough VTE and subsequent recurrences were objectively verified. Outcomes
      with different treatment strategies were compared with Cox proportional hazards
      regression. RESULTS: We registered 212 patients with breakthrough VTE. Of those,
      59% had adenocarcinoma and 73% had known metastases. At the time of the
      breakthrough event, 70% were on low-molecular-weight heparin (LMWH) and 27% on a
      vitamin K antagonist (VKA); 70% had a therapeutic or supratherapeutic dose. After
      breakthrough the regimen was: unchanged therapeutic dose in 33%, dose increased
      in 31%, switched to another drug in 24%; and other management in 11%. During the
      following 3 months 11% had another VTE, 8% had major bleeding and 27% died. Of
      the survivors, 74% had residual thrombosis symptoms. Additional VTE recurrence
      was less common with LMWH than with a VKA (hazard ratio [HR], 0.28; 95%
      confidence interval [CI], 0.11-0.70) but similar with unchanged or increased
      anticoagulant intensity (HR, 1.09; 95% CI, 0.45-2.63). The bleeding rate did not
      increase significantly with dose escalation. CONCLUSION: Morbidity and mortality
      are high after recurrence of cancer-related VTE despite anticoagulation. Further
      treatment appears to be more effective with LMWH than with a VKA.

PMID- 25851123
TI  - Methodological considerations on push-out tests in Endodontics.

PMID- 25851124
TI  - New directions in qualitative research in psychology.
AB  - Qualitative Research gains increasing popularity in the field of Psychology. With
      the renewed interest, there are, however, also some risks related to the
      overhomogenization and increasing standardization of qualitative methods. This
      special issue is dedicated to clarify some of the existing misconceptions of
      qualitative research and to discuss its potentials for the field of psychology in
      light of recent endeavors to overcome paradigmatic battles and a re-orientation
      to the specifities of psychology. The issue comprises a discussion from workshop
      on the future of qualitative research in psychology organized at Aalborg
      University, and several contributions that resulted from it. 

PMID- 25851125
TI  - Notch Receptor-Ligand Engagement Maintains Hematopoietic Stem Cell Quiescence and
      Niche Retention.
AB  - Notch is long recognized as a signaling molecule important for stem cell self
      renewal and fate determination. Here, we reveal a novel adhesive role of Notch
      ligand engagement in hematopoietic stem and progenitor cells (HSPCs). Using mice
      with conditional loss of O-fucosylglycans on Notch EGF-like repeats important for
      the binding of Notch ligands, we report that HSPCs with faulty ligand binding
      ability display enhanced cycling accompanied by increased egress from the marrow,
      a phenotype mainly attributed to their reduced adhesion to Notch ligand
      expressing stromal cells and osteoblastic cells and their altered occupation in
      osteoblastic niches. Adhesion to Notch ligand-bearing osteoblastic or stromal
      cells inhibits wild type but not O-fucosylglycan-deficient HSPC cycling,
      independent of RBP-JK -mediated canonical Notch signaling. Furthermore, Notch
      ligand neutralizing antibodies induce RBP-JK -independent HSPC egress and
      enhanced HSPC mobilization. We, therefore, conclude that Notch receptor-ligand
      engagement controls HSPC quiescence and retention in the marrow niche that is
      dependent on O-fucosylglycans on Notch.

PMID- 25851126
TI  - Effects of cyclodextrins on GM1-gangliosides in fibroblasts from GM1
      gangliosidosis patients.
AB  - OBJECTIVES: GM1-gangliosidosis is an inherited disorder characterized by the
      accumulation of GM1-gangliosides in many tissues and organs, particularly in the
      brain. Currently, there is no treatment available for patients with ganglioside
      storage diseases. Therefore, we investigated the effects of cyclodextrins (CyDs)
      on the GM1-ganglioside level in EA1 cells, fibroblasts from patients with GM1
      gangliosidosis. METHODS: The concentrations of cholesterol and phospholipids in
      supernatants were determined by Cholesterol E-test Wako and Phospholipid C-test
      Wako, respectively. The effects of CyDs on GM1-ganglioside levels in EA1 cells
      using fluorescence-labelled cholera toxin B-subunit, which can bind to GM1
      gangliosides specifically, were investigated by flow cytometry and confocal laser
      scanning microscopy. KEY FINDINGS: The treatment with methylated CyDs,
      hydroxypropylated CyDs and branched CyDs decreased GM1-ganglioside levels in EA1
      cells at 1 mm for 24 h. Unexpectedly, there was no significant change in the
      efflux of cholesterol or phospholipids from the cells after treatment with CyDs
      under the same experimental conditions, indicating that the efflux of membrane
      components is not associated with down-regulation of GM1-ganglioside levels in
      EA1 cells upon CyDs treatment. CONCLUSIONS: CyDs may have the potential as drugs
      for GM1-gangliosidosis, although the mechanism should be thereafter clarified.

PMID- 25851127
TI  - Quest for highly connected metal-organic framework platforms: rare-earth
      polynuclear clusters versatility meets net topology needs.
AB  - Gaining control over the assembly of highly porous rare-earth (RE) based metal
      organic frameworks (MOFs) remains challenging. Here we report the latest
      discoveries on our continuous quest for highly connected nets. The topological
      exploration based on the noncompatibility of a 12-connected RE polynuclear
      carboxylate-based cluster, points of extension matching the 12 vertices of the
      cuboctahedron (cuo), with 3-connected organic ligands led to the discovery of two
      fascinating and highly connected minimal edge-transitive nets, pek and aea. The
      reduced symmetry of the employed triangular tricarboxylate ligand, as compared to
      the prototype highly symmetrical 1,3,5-benzene(tris)benzoic acid guided the
      concurrent occurrence of nonanuclear [RE9(MU3-OH)12(MU3-O)2(O2C-)12] and
      hexanuclear [RE6(OH)8(O2C-)8] carboxylate-based clusters as 12-connected and 8
      connected molecular building blocks in the structure of a 3-periodic pek-MOF
      based on a novel (3,8,12)-c trinodal net. The use of a tricarboxylate ligand with
      modified angles between carboxylate moieties led to the formation of a second MOF
      containing solely nonanuclear clusters and exhibiting once more a novel and a
      highly connected (3,12,12)-c trinodal net with aea topology. Notably, it is the
      first time that RE-MOFs with double six-membered ring (d6R) secondary building
      units are isolated, representing therefore a critical step forward toward the
      design of novel and highly coordinated materials using the supermolecular
      building layer approach while considering the d6Rs as building pillars. Lastly,
      the potential of these new MOFs for gas separation/storage was investigated by
      performing gas adsorption studies of various probe gas molecules over a wide
      range of pressures. Noticeably, pek-MOF-1 showed excellent volumetric CO2 and CH4
      uptakes at high pressures. 

PMID- 25851129
TI  - Epoch-based likelihood models reveal no evidence for accelerated evolution of
      viviparity in squamate reptiles in response to cenozoic climate change.
AB  - A broad scale analysis of the evolution of viviparity across nearly 4,000 species
      of squamates revealed that origins increase in frequency toward the present,
      raising the question of whether rates of change have accelerated. We here use
      simulations to show that the increased frequency is within the range expected
      given that the number of squamate lineages also increases with time. Novel, epoch
      based methods implemented in BEAST (which allow rates of discrete character
      evolution to vary across time-slices) also give congruent results, with recent
      epochs having very similar rates to older epochs. Thus, contrary to expectations,
      there was no accelerated burst of origins of viviparity in response to global
      cooling during the Cenozoic or glacial cycles during the Plio-Pleistocene.
      However, if one accepts the conventional view that viviparity is more likely to
      evolve than to be lost, and also the evidence here that viviparity has evolved
      with similar regularity throughout the last 200 Ma, then the absence of large,
      ancient clades of viviparous squamates (analogs to therian mammals) requires
      explanation. Viviparous squamate lineages might be more prone to extinction than
      are oviparous lineages, due to their prevalance at high elevations and latitudes
      and thus greater susceptibility to climate fluctuations. If so, the directional
      bias in character evolution would be offset by the bias in extinction rates.

PMID- 25851130
TI  - Farmed and wild sea bass (Dicentrarchus labrax) volatile metabolites: a
      comparative study by SPME-GC/MS.
AB  - BACKGROUND: Farmed and wild European sea bass (Dicentrarchus labrax) could be
      distinguished by its volatile metabolites, an issue not addressed until now. The
      aim of this work was to study these metabolites by solid-phase microextraction
      followed by gas chromatography/mass spectrometry (SPME-GC/MS). RESULTS: Both
      farmed and wild sea bass have a great number of volatile metabolites, most of
      them being in low concentrations. These include alcohols, aldehydes, ketones,
      alkylfurans, acids, aliphatic and aromatic hydrocarbons, terpenes, sulfur and
      nitrogen derivatives, 2,6-di-tert-butyl-4-methylphenol and one derived compound,
      as well as 2,4,7,9-tetramethyl-5-decyne-4,7-diol, this latter compound presumably
      resulting from environmental contamination. Important differences have been
      detected between both types of sea bass, and also among individuals inside each
      group. Farmed specimens are richer in volatile metabolites than the wild
      counterparts; however, these latter, in general, contain a high number and
      abundance of metabolites resulting from microbial and enzymatic non-oxidative
      activity than the former. CONCLUSIONS: Clear differences in the volatile
      metabolites of wild and farmed sea bass have been found. A great deal of valuable
      information on sea bass volatile metabolites has been obtained, which can be
      useful in understanding certain aspects of the quality and safety of raw and
      processed sea bass.

PMID- 25851131
TI  - Cochliopodium arabianum n. sp. (Amorphea, Amoebozoa).
AB  - A new species of Cochliopodium isolated from freshwater at Arabia Lake in
      Lithonia, GA, USA is described based on light microscopic morphology, fine
      structure, and molecular genetic evidence. Cochliopodium arabianum n. sp.,
      previously labeled as "isolate Con1" in prior publications, has been shown to
      group within the genus Cochliopodium in our molecular phylogenetic analysis.
      Light microscopy and fine structure evidence indicates the new isolate not only
      shares characters of the genus but also unique distinctive features.
      Cochliopodium arabianum n. sp. is typically round when stationary; or oval to
      sometimes broadly flabellate or triangular in shape during locomotion, with
      average length of 35 MUm and breadth of 51 MUm. Fine structure evidence indicates
      C. arabianum n. sp. has tower-like scales, lacking a terminal spine, sharing high
      similarity with its closest relative C. actinophorum. However, the scales of C.
      arabianum n. sp. are unique in height and the breadth of the base plate. Both
      morphological and molecular data, including SSU-rDNA and COI, indicate that this
      new species falls in a clade sufficiently different from other species to suggest
      that it is a valid new species.

PMID- 25851132
TI  - Does long-term cultivation of saplings under elevated CO2 concentration influence
      their photosynthetic response to temperature?
AB  - BACKGROUND AND AIMS: Plants growing under elevated atmospheric CO2 concentrations
      often have reduced stomatal conductance and subsequently increased leaf
      temperature. This study therefore tested the hypothesis that under long-term
      elevated CO2 the temperature optima of photosynthetic processes will shift
      towards higher temperatures and the thermostability of the photosynthetic
      apparatus will increase. METHODS: The hypothesis was tested for saplings of
      broadleaved Fagus sylvatica and coniferous Picea abies exposed for 4-5 years to
      either ambient (AC; 385 umol mol(-1)) or elevated (EC; 700 umol mol(-1)) CO2
      concentrations. Temperature response curves of photosynthetic processes were
      determined by gas-exchange and chlorophyll fluorescence techniques. KEY RESULTS:
      Initial assumptions of reduced light-saturated stomatal conductance and increased
      leaf temperatures for EC plants were confirmed. Temperature response curves
      revealed stimulation of light-saturated rates of CO2 assimilation (Amax) and a
      decline in photorespiration (RL) as a result of EC within a wide temperature
      range. However, these effects were negligible or reduced at low and high
      temperatures. Higher temperature optima (Topt) of Amax, Rubisco carboxylation
      rates (VCmax) and RL were found for EC saplings compared with AC saplings.
      However, the shifts in Topt of Amax were instantaneous, and disappeared when
      measured at identical CO2 concentrations. Higher values of Topt at elevated CO2
      were attributed particularly to reduced photorespiration and prevailing
      limitation of photosynthesis by ribulose-1,5-bisphosphate (RuBP) regeneration.
      Temperature response curves of fluorescence parameters suggested a negligible
      effect of EC on enhancement of thermostability of photosystem II photochemistry.
      CONCLUSIONS: Elevated CO2 instantaneously increases temperature optima of Amax
      due to reduced photorespiration and limitation of photosynthesis by RuBP
      regeneration. However, this increase disappears when plants are exposed to
      identical CO2 concentrations. In addition, increased heat-stress tolerance of
      primary photochemistry in plants grown at elevated CO2 is unlikely. The
      hypothesis that long-term cultivation at elevated CO2 leads to acclimation of
      photosynthesis to higher temperatures is therefore rejected. Nevertheless,
      incorporating acclimation mechanisms into models simulating carbon flux between
      the atmosphere and vegetation is necessary.

PMID- 25851133
TI  - Can the exceptional chilling tolerance of C4 photosynthesis found in Miscanthus *
      giganteus be exceeded? Screening of a novel Miscanthus Japanese germplasm
      collection.
AB  - BACKGROUND AND AIMS: A clone of the hybrid perennial C4 grass Miscanthus *
      giganteus (Mxg) is known for achieving exceptionally high rates of leaf CO2
      uptake during chilling. This is a requisite of success in the early spring, as is
      the ability of the leaves to survive occasional frosts. The aim of this study was
      to search for genotypes with greater potential than Mxg for photosynthesis and
      frost survival under these conditions. METHODS: A total of 864 accessions
      representing 164 local populations of M. sacchariflorus (Msa), M. sinensis (Msi)
      and M. tinctorius (Mti) collected across Japan were studied. Accessions whose
      leaves survived a natural late frost in the field were screened for high maximum
      photosystem II efficiency (Fv/Fm) following chilling weather, as an indicator of
      their capacity for light-limited photosynthesis. Those showing the highest Fv/Fm
      were transferred to a high-light-controlled environment and maintained at
      chilling temperatures, where they were further screened for their capacities for
      high-light-limited and light-saturated leaf uptake of CO2 (PhiCO2,max and Asat,
      respectively). KEY RESULTS: For the first time, relatives of Mxg with
      significantly superior capacities for photosynthesis at chilling temperatures
      were identified. Msa accession '73/2' developed leaves in the spring that
      survived night-time frost, and during growth under chilling maintained a
      statistically significant 79 % higher PhiCO2,max, as a measure of light-limited
      photosynthesis, and a 70 % higher Asat, as a measure of light-saturated
      photosynthesis. A second Msa accession, '73/3' also showed significantly higher
      rates of leaf uptake of CO2. CONCLUSIONS: As remarkable as Mxg has proved in its
      chilling tolerance of C4 photosynthesis, this study shows that there is still
      value and potential in searching for yet more superior tolerance. Msa accession
      '73/2' shows rates of light-limited and light-saturated photosynthesis at
      chilling temperatures that are comparable with those of the most cold-tolerant C3
      species. This adds further proof to the thesis that C4 photosynthesis is not
      inherently limited to warm climates.

PMID- 25851134
TI  - What functional strategies drive drought survival and recovery of perennial
      species from upland grassland?
AB  - BACKGROUND AND AIMS: Extreme climatic events such as severe droughts are expected
      to increase with climate change and to limit grassland perennity. The present
      study aimed to characterize the adaptive responses by which temperate herbaceous
      grassland species resist, survive and recover from a severe drought and to
      explore the relationships between plant resource use and drought resistance
      strategies. METHODS: Monocultures of six native perennial species from upland
      grasslands and one Mediterranean drought-resistant cultivar were compared under
      semi-controlled and non-limiting rooting depth conditions. Above- and below
      ground traits were measured under irrigation in spring and during drought in
      summer (50 d of withholding water) in order to characterize resource use and
      drought resistance strategies. Plants were then rehydrated and assessed for
      survival (after 15 d) and recovery (after 1 year). KEY RESULTS: Dehydration
      avoidance through water uptake was associated with species that had deep roots
      (>1.2 m) and high root mass (>4 kg m(-3)). Cell membrane stability ensuring
      dehydration tolerance of roots and meristems was positively correlated with
      fructan content and negatively correlated with sucrose content. Species that
      survived and recovered best combined high resource acquisition in spring (leaf
      elongation rate >9 mm d(-1) and rooting depth >1.2 m) with both high dehydration
      avoidance and tolerance strategies. CONCLUSIONS: Most of the native forage
      species, dominant in upland grassland, were able to survive and recover from
      extreme drought, but with various time lags. Overall the results suggest that the
      wide range of interspecific functional strategies for coping with drought may
      enhance the resilience of upland grassland plant communities under extreme
      drought events.

PMID- 25851135
TI  - From observations to experiments in phenology research: investigating climate
      change impacts on trees and shrubs using dormant twigs.
AB  - BACKGROUND AND AIMS: Climate change is advancing the leaf-out times of many plant
      species and mostly extending the growing season in temperate ecosystems.
      Laboratory experiments using twig cuttings from woody plant species present an
      affordable, easily replicated approach to investigate the relative importance of
      factors such as winter chilling, photoperiod, spring warming and frost tolerance
      on the leafing-out times of plant communities. This Viewpoint article
      demonstrates how the results of these experiments deepen our understanding beyond
      what is possible via analyses of remote sensing and field observation data, and
      can be used to improve climate change forecasts of shifts in phenology, ecosystem
      processes and ecological interactions. SCOPE: The twig method involves cutting
      dormant twigs from trees, shrubs and vines on a single date or at intervals over
      the course of the winter and early spring, placing them in containers of water in
      controlled environments, and regularly recording leaf-out, flowering or other
      phenomena. Prior to or following leaf-out or flowering, twigs may be assigned to
      treatment groups for experiments involving temperature, photoperiod, frost,
      humidity and more. Recent studies using these methods have shown that winter
      chilling requirements and spring warming strongly affect leaf-out and flowering
      times of temperate trees and shrubs, whereas photoperiod requirements are less
      important than previously thought for most species. Invasive plant species have
      weaker winter chilling requirements than native species in temperate ecosystems,
      and species that leaf-out early in the season have greater frost tolerance than
      later leafing species. CONCLUSIONS: This methodology could be extended to
      investigate additional drivers of leaf-out phenology, leaf senescence in the
      autumn, and other phenomena, and could be a useful tool for education and
      outreach. Additional ecosystems, such as boreal, southern hemisphere and sub
      tropical forests, could also be investigated using dormant twigs to determine the
      drivers of leaf-out times and how these ecosystems will be affected by climate
      change.

PMID- 25851136
TI  - Extreme defoliation reduces tree growth but not C and N storage in a winter
      deciduous species.
AB  - BACKGROUND AND AIMS: There is a growing concern about how forests will respond to
      increased herbivory associated with climate change. Carbon (C) and nitrogen (N)
      limitation are hypothesized to cause decreasing growth after defoliation, and
      eventually mortality. This study examines the effects of a natural and massive
      defoliation by an insect on mature trees' C and N storage, which have rarely been
      studied together, particularly in winter-deciduous species. METHODS: Survival,
      growth rate, carbon [C, as non-structural carbohydrate (NSC) concentration] and
      nitrogen (N) storage, defences (tannins and total polyphenols), and re-foliation
      traits were examined in naturally defoliated and non-defoliated adult trees of
      the winter-deciduous temperate species Nothofagus pumilio 1 and 2 years after a
      massive and complete defoliation caused by the caterpillar of Ormiscodes
      amphimone (Saturniidae) during summer 2009 in Patagonia. KEY RESULTS: Defoliated
      trees did not die but grew significantly less than non-defoliated trees for at
      least 2 years after defoliation. One year after defoliation, defoliated trees had
      similar NSC and N concentrations in woody tissues, higher polyphenol
      concentrations and lower re-foliation than non-defoliated trees. In the second
      year, however, NSC concentrations in branches were significantly higher in
      defoliated trees while differences in polyphenols and re-foliation disappeared
      and decreased, respectively. CONCLUSIONS: The significant reduction in growth
      following defoliation was not caused by insufficient C or N availability, as
      frequently assumed; instead, it was probably due to growth limitations due to
      factors other than C or N, or to preventative C allocation to storage. This study
      shows an integrative approach to evaluating plant growth limitations in response
      to disturbance, by examining major resources other than C (e.g. N), and other C
      sinks besides storage and growth (e.g. defences and re-foliation).

PMID- 25851137
TI  - A theoretical approach to the relationship between wettability and surface
      microstructures of epidermal cells and structured cuticles of flower petals.
AB  - BACKGROUND AND AIMS: The epidermal surface of a flower petal is composed of
      convex cells covered with a structured cuticle, and the roughness of the surface
      is related to the wettability of the petal. If the surface remains wet for an
      excessive amount of time the attractiveness of the petal to floral visitors may
      be impaired, and adhesion of pathogens may be promoted. However, it remains
      unclear how the epidermal cells and structured cuticle contribute to surface
      wettability of a petal. METHODS: By considering the additive effects of the
      epidermal cells and structured cuticle on petal wettability, a thermodynamic
      model was developed to predict the wetting mode and contact angle of a water
      droplet at a minimum free energy. Quantitative relationships between petal
      wettability and the geometries of the epidermal cells and the structured cuticle
      were then estimated. Measurements of contact angles and anatomical traits of
      petals were made on seven herbaceous species commonly found in alpine habitats in
      eastern Nepal, and the measured wettability values were compared with those
      predicted by the model using the measured geometries of the epidermal cells and
      structured cuticles. KEY RESULTS: The model indicated that surface wettability
      depends on the height and interval between cuticular steps, and on a height-to
      width ratio for epidermal cells if a thick hydrophobic cuticle layer covers the
      surface. For a petal epidermis consisting of lenticular cells, a repellent
      surface results when the cuticular step height is greater than 0.85 um and the
      height-to-width ratio of the epidermal cells is greater than 0.3. For an
      epidermis consisting of papillate cells, a height-to-width ratio of greater than
      1.1 produces a repellent surface. In contrast, if the surface is covered with a
      thin cuticle layer, the petal is highly wettable (hydrophilic) irrespective of
      the roughness of the surface. These predictions were supported by the
      measurements of petal wettability made on flowers of alpine species. CONCLUSIONS:
      The results indicate that surface roughness caused by epidermal cells and a
      structured cuticle produces a wide range of petal wettability, and that this can
      be successfully modelled using a thermodynamic approach.

PMID- 25851138
TI  - Modelling snow cover duration improves predictions of functional and taxonomic
      diversity for alpine plant communities.
AB  - BACKGROUND AND AIMS: Quantifying relationships between snow cover duration and
      plant community properties remains an important challenge in alpine ecology. This
      study develops a method to estimate spatial variation in energy availability in
      the context of a topographically complex, high-elevation watershed, which was
      used to test the explanatory power of environmental gradients both with and
      without snow cover in relation to taxonomic and functional plant diversity.
      METHODS: Snow cover in the French Alps was mapped at 15-m resolution using
      Landsat imagery for five recent years, and a generalized additive model (GAM) was
      fitted for each year linking snow to time and topography. Predicted snow cover
      maps were combined with air temperature and solar radiation data at daily
      resolution, summed for each year and averaged across years. Equivalent growing
      season energy gradients were also estimated without accounting for snow cover
      duration. Relationships were tested between environmental gradients and diversity
      metrics measured for 100 plots, including species richness, community-weighted
      mean traits, functional diversity and hyperspectral estimates of canopy
      chlorophyll content. KEY RESULTS: Accounting for snow cover in environmental
      variables consistently led to improved predictive power as well as more
      ecologically meaningful characterizations of plant diversity. Model parameters
      differed significantly when fitted with and without snow cover. Filtering solar
      radiation with snow as compared without led to an average gain in R(2) of 0.26
      and reversed slope direction to more intuitive relationships for several
      diversity metrics. CONCLUSIONS: The results show that in alpine environments high
      resolution data on snow cover duration are pivotal for capturing the spatial
      heterogeneity of both taxonomic and functional diversity. The use of climate
      variables without consideration of snow cover can lead to erroneous predictions
      of plant diversity. The results further indicate that studies seeking to predict
      the response of alpine plant communities to climate change need to consider
      shifts in both temperature and nival regimes.

PMID- 25851139
TI  - How tree species fill geographic and ecological space in eastern North America.
AB  - BACKGROUND AND AIMS: Ecologists broadly accept that the number of species present
      within a region balances regional processes of immigration and speciation against
      competitive and other interactions between populations that limit distribution
      and constrain diversity. Although ecological theory has, for a long time,
      addressed the premise that ecological space can be filled to 'capacity' with
      species, only with the availability of time-calibrated phylogenies has it been
      possible to test the hypothesis that diversification slows as the number of
      species in a region increases. Focusing on the deciduous trees of eastern North
      America, this study tested predictions from competition theory concerning the
      distribution and abundance of species. METHODS: Local assemblages of trees
      tabulated in a previous study published in 1950 were analysed. Assemblages were
      ordinated with respect to species composition by non-metric multidimensional
      scaling (NMS). Distributions of trees were analysed by taxonomically nested
      analysis of variance, discriminant analysis based on NMS scores, and canonical
      correlation analysis of NMS scores and Bioclim climate variables. KEY RESULTS:
      Most of the variance in species abundance and distribution was concentrated among
      closely related (i.e. congeneric) species, indicating evolutionary lability.
      Species distribution and abundance were unrelated to the number of close
      relatives, suggesting that competitive effects are diffuse. Distances between
      pairs of congeneric species in NMS space did not differ significantly from
      distances between more distantly related species, in contrast to the predictions
      of both competitive habitat partitioning and ecological sorting of species.
      CONCLUSIONS: Eastern deciduous forests of North America do not appear to be
      saturated with species. The distributions and abundances of individual species
      provide little evidence of being shaped by competition from related (i.e.
      ecologically similar) species and, by inference, that diversification is
      constrained by interspecific competition.

PMID- 25851140
TI  - Redox markers for drought-induced nodule senescence, a process occurring after
      drought-induced senescence of the lowest leaves in soybean (Glycine max).
AB  - BACKGROUND AND AIMS: Water is an increasingly scarce resource that limits crop
      productivity in many parts of the world, and the frequency and severity of
      drought are predicted to increase as a result of climate change. Improving
      tolerance to drought stress is therefore important for maximizing future crop
      yields. The aim of this study was to compare the effects of drought on soybean
      (Glycine max) leaves and nodules in order to define phenotypic markers and
      changes in cellular redox state that characterize the stress response in
      different organs, and to characterize the relationships between leaf and nodule
      senescence during drought. METHODS: Leaf and crown nodule metabolite pools were
      measured together with leaf and soil water contents, and leaf chlorophyll, total
      protein contents and chlorophyll a fluorescence quenching parameters in nodulated
      soybeans that were grown under either well-watered conditions or deprived of
      water for up to 21 d. KEY RESULTS: Ureides, ascorbate, protein, chlorophyll and
      the ratios of variable chlorophyll a fluorescence (Fv') to maximal chlorophyll a
      fluorescence (Fm') fell to levels below detection in the oldest leaves after 21 d
      of drought. While these drought-induced responses were not observed in the
      youngest leaf ranks, the Fv'/Fm' ratios, pyridine nucleotide levels and the
      reduction state of the ascorbate pool were lower in all leaf ranks after 21 d of
      drought. In contrast to leaves, total nodule protein, pyridine nucleotides,
      ureides, ascorbate and glutathione contents increased as a result of the drought
      treatment. However, the nodule ascorbate pool was significantly less reduced as a
      result of drought. Higher levels of transcripts encoding two peroxiredoxins were
      detected in nodules exposed to drought stress but senescence-associated
      transcripts and other mRNAs encoding redox-related proteins were similar under
      both conditions. CONCLUSIONS: While the physiological impact of the drought was
      perceived throughout the shoot, stress-induced senescence occurred only in the
      oldest leaf ranks. At this stage, a number of drought-induced changes in nodule
      metabolites were observed but no metabolite or transcript markers of senescence
      could be detected. It is concluded that stress-induced senescence in the lowest
      leaf ranks precedes nodule senescence, suggesting that leaves of low
      photosynthetic capacity are sacrificed in favour of nodule nitrogen metabolism.

PMID- 25851141
TI  - Red:far-red light conditions affect the emission of volatile organic compounds
      from barley (Hordeum vulgare), leading to altered biomass allocation in
      neighbouring plants.
AB  - BACKGROUND AND AIMS: Volatile organic compounds (VOCs) play various roles in
      plant-plant interactions, and constitutively produced VOCs might act as a cue to
      sense neighbouring plants. Previous studies have shown that VOCs emitted from the
      barley (Hordeum vulgare) cultivar 'Alva' cause changes in biomass allocation in
      plants of the cultivar 'Kara'. Other studies have shown that shading and the low
      red:far-red (R:FR) conditions that prevail at high plant densities can reduce the
      quantity and alter the composition of the VOCs emitted by Arabidopsis thaliana,
      but whether this affects plant-plant signalling remains unknown. This study
      therefore examines the effects of far-red light enrichment on VOC emissions and
      plant-plant signalling between 'Alva' and 'Kara'. METHODS: The proximity of
      neighbouring plants was mimicked by supplemental far-red light treatment of VOC
      emitter plants of barley grown in growth chambers. Volatiles emitted by 'Alva'
      under control and far-red light-enriched conditions were analysed using gas
      chromatography-mass spectrometry (GC-MS). 'Kara' plants were exposed to the VOC
      blend emitted by the 'Alva' plants that were subjected to either of the light
      treatments. Dry matter partitioning, leaf area, stem and total root length were
      determined for 'Kara' plants exposed to 'Alva' VOCs, and also for 'Alva' plants
      exposed to either control or far-red-enriched light treatments. KEY RESULTS:
      Total VOC emissions by 'Alva' were reduced under low R:FR conditions compared
      with control light conditions, although individual volatile compounds were found
      to be either suppressed, induced or not affected by R:FR. The altered composition
      of the VOC blend emitted by 'Alva' plants exposed to low R:FR was found to affect
      carbon allocation in receiver plants of 'Kara'. CONCLUSIONS: The results indicate
      that changes in R:FR light conditions influence the emissions of VOCs in barley,
      and that these altered emissions affect VOC-mediated plant-plant interactions.

PMID- 25851142
TI  - A climate change context for the decline of a foundation tree species in south
      western Australia: insights from phylogeography and species distribution
      modelling.
AB  - BACKGROUND AND AIMS: A worldwide increase in tree decline and mortality has been
      linked to climate change and, where these represent foundation species, this can
      have important implications for ecosystem functions. This study tests a combined
      approach of phylogeographic analysis and species distribution modelling to
      provide a climate change context for an observed decline in crown health and an
      increase in mortality in Eucalyptus wandoo, an endemic tree of south-western
      Australia. METHODS: Phylogeographic analyses were undertaken using restriction
      fragment length polymorphism analysis of chloroplast DNA in 26 populations across
      the species distribution. Parsimony analysis of haplotype relationships was
      conducted, a haplotype network was prepared, and haplotype and nucleotide
      diversity were calculated. Species distribution modelling was undertaken using
      Maxent models based on extant species occurrences and projected to climate models
      of the last glacial maximum (LGM). KEY RESULTS: A structured pattern of diversity
      was identified, with the presence of two groups that followed a climatic gradient
      from mesic to semi-arid regions. Most populations were represented by a single
      haplotype, but many haplotypes were shared among populations, with some having
      widespread distributions. A putative refugial area with high haplotype diversity
      was identified at the centre of the species distribution. Species distribution
      modelling showed high climatic suitability at the LGM and high climatic stability
      in the central region where higher genetic diversity was found, and low
      suitability elsewhere, consistent with a pattern of range contraction.
      CONCLUSIONS: Combination of phylogeography and paleo-distribution modelling can
      provide an evolutionary context for climate-driven tree decline, as both can be
      used to cross-validate evidence for refugia and contraction under harsh climatic
      conditions. This approach identified a central refugial area in the test species
      E. wandoo, with more recent expansion into peripheral areas from where it had
      contracted at the LGM. This signature of contraction from lower rainfall areas is
      consistent with current observations of decline on the semi-arid margin of the
      range, and indicates low capacity to tolerate forecast climatic change.
      Identification of a paleo-historical context for current tree decline enables
      conservation interventions to focus on maintaining genetic diversity, which
      provides the evolutionary potential for adaptation to climate change.

PMID- 25851143
TI  - Neonatal leukaemia cutis.
AB  - Neonatal leukaemia cutis is a significant neoplasm that may represent a cutaneous
      manifestation of systemic leukaemia, usually of myeloblastic type. Rarely, it may
      be or appear to be limited to skin, in which case it is called neonatal
      aleukaemic leukaemia cutis. By definition, it presents within the first 4 weeks
      of life and often has a 'blueberry muffin baby' appearance of magenta coloured
      nodules affecting almost any area of the skin, usually sparing mucous membranes,
      palms and soles. This clinical pattern is more commonly associated with neonatal
      infections such rubella and toxoplasmosis, and may be evident with other neonatal
      neoplasms such as neuroblastoma. Due to the morbidity associated with
      chemotherapy and reported cases of spontaneous remission without systemic
      progression in those with neonatal aleukaemic leukaemia cutis without 11q23
      translocation, the authors not treating the child with chemotherapy, but to
      simply monitor for fading of the violaceous nodules, and watch for possible signs
      of systemic leukaemia. 

PMID- 25851144
TI  - What understanding tendon cell differentiation can teach us about pathological
      tendon ossification.
AB  - Tendons are the structures that attach muscles to bones and transmit mechanical
      forces. Tendon cells are composed of mature tenocytes and a rare population of
      tendon stem cells. Both cell types ensure homeostasis and repair of tendon
      extracellular matrix to guarantee its specific mechanical properties. Moreover,
      tendon cells seem to present a marked potential for trans-differentiation,
      predominantly into the chondrocyte and osteoblast lineages. In this review
      article, we first present chronic tendon pathologies associated with abnormal
      ossification, such as spondyloarthritis and calcifying tendinopathy, and discuss
      how tendon cell differentiation and trans-differentiation may participate in
      these diseases. We moreover present the factors known to influence tendon cell
      differentiation and trans-differentiation, with a particular emphasis on
      extracellular environment, mechanical stimulation and several soluble factors
      that can tip the balance toward one or another lineage. A better understanding of
      the neglected tendon cell biology may be extremely useful to understand the
      pathological mechanisms of spondyloarthritis and calcifying tendinopathy. 

PMID- 25851145
TI  - Evaluation of Vessel Sealing Performance Among Ultrasonic Devices in a Porcine
      Model.
AB  - BACKGROUND: As new technologies emerge, it is imperative to define which new
      devices are most likely to provide a reproducible, effective result for the
      patient and surgeon. The purpose of our study was to analyze 3 commercially
      available ultrasonic energy devices; the Sonicision (SC), the Harmonic ACE (HA),
      and the THUNDERBEAT (TB). MATERIAL AND METHODS: Eight female Yorkshire pigs were
      used for data collection and vessel harvest. Three devices were evaluated and
      compared with each other with respect to seal failure and cutting speed in vivo.
      After vessel harvest, one end of the fragment was sent for histological
      evaluation, and the other was used for burst pressure measurement testing in a
      blinded fashion. The coagulation and cut levels of all the generators were set up
      at a similar and constant level. RESULTS: Eighty-four vessels (47 arteries and 37
      veins) were tested. Mean vessel diameter was equal among the groups. Cutting
      speed was significantly faster with TB (3.4 +/- 0.7 seconds) than SC or HA (5.8
      +/- 2.4 and 6.1 +/- 3.1 seconds; P < .0001). Burst pressure trended higher after
      ligation with TB (505.4 +/- 349.4 mm Hg) than SC and HA (435.8 +/- 403.0 and
      437.6 +/- 291.3 mm Hg). There were 2 seal failures in the SC group and HA group
      and none in the TB group. Histologically, the perpendicular width of tissue seal
      with TB (1.250 +/- 0.55 mm) was significantly longer than that of the SC and the
      HA (0.772 +/- 0.23 and 0.686 +/- 0.23 mm; P < .0001). CONCLUSIONS: TB has proven
      to provide the most rapid and reliable seal. Therefore, TB may be safer and may
      decrease time during surgical procedures.

PMID- 25851146
TI  - Neurosurgical Assessment of Metrics Including Judgment and Dexterity Using the
      Virtual Reality Simulator NeuroTouch (NAJD Metrics).
AB  - Advances in computer-based technology has created a significant opportunity for
      implementing new training paradigms in neurosurgery focused on improving skill
      acquisition, enhancing procedural outcome, and surgical skills assessment.
      NeuroTouch is a computer-based virtual reality system that can generate output
      data known as metrics from operator performance during simulated brain tumor
      resection. These measures of quantitative assessment are used to track and
      compare psychomotor performance during simulated operative procedures. Data
      output from the NeuroTouch system is recorded in a comma-separated values file.
      Data mining from this file and subsequent metrics development requires the use of
      sophisticated software and engineering expertise. In this article, we introduce a
      system to extract a series of new metrics using the same data file using Excel
      software. Based on the data contained in the NeuroTouch comma-separated values
      file, 13 novel NeuroTouch metrics were developed and classified. Tier 1 metrics
      include blood loss, tumor percentage resected, and total simulated normal brain
      volume removed. Tier 2 metrics include total instrument tip path length, maximum
      force applied, sum of forces utilized, and average forces utilized by the
      simulated ultrasonic aspirator and suction instrument along with pedal activation
      frequency of the ultrasonic aspirator. Advanced tier 2 metrics include instrument
      tips average separation distance, efficiency index, ultrasonic aspirator path
      length index, coordination index, and ultrasonic aspirator bimanual forces ratio.
      This system of data extraction provides researchers expedited access for
      analyzing the data files available for NeuroTouch platform to assess the multiple
      psychomotor and cognitive neurosurgical skills involved in complex surgical
      procedures. 

PMID- 25851147
TI  - Lazare Riviere (1589-1655 AD), the Pioneer Pharmacologist, Anatomist, and
      Surgeon, Who Gave the First Modern Description of an Aortic Valve Failure.

PMID- 25851148
TI  - Design principles of a conditional futile cycle exploited for regulation.
AB  - In this report, we characterize the design principles of futile cycling in
      providing rapid adaptation by regulatory proteins that act as environmental
      sensors. In contrast to the energetically wasteful futile cycles that are avoided
      in metabolic pathways, here we describe a conditional futile cycle exploited for
      a regulatory benefit. The FNR (fumarate and nitrate reduction) cycle in
      Escherichia coli operates under two regimes - a strictly futile cycle in the
      presence of O2 and as a pathway under anoxic conditions. The computational
      results presented here use FNR as a model system and provide evidence that
      cycling of this transcription factor and its labile sensory cofactor between
      active and inactive states affords rapid signaling and adaptation. We modify a
      previously developed mechanistic model to examine a family of FNR models each
      with different cycling speeds but mathematically constrained to be otherwise
      equivalent, and we identify a trade-off between energy expenditure and response
      time that can be tuned by evolution to optimize cycling rate of the FNR system
      for a particular ecological context. Simulations mimicking experiments with
      proposed double mutant strains offer suggestions for experimentally testing our
      predictions and identifying potential fitness effects. Our approach provides a
      computational framework for analyzing other conditional futile cycles, which when
      placed in their larger biological context may be found to confer advantages to
      the organism. 

PMID- 25851149
TI  - Urinary iodine level and its determinants in pregnant women of Shanghai, China.
AB  - It is known that iodine deficiency during pregnancy can interfere with normal
      fetal growth and development. However, iodine levels of pregnant women in
      Shanghai, China, and factors that could influence its levels remain unclear. A
      total of 916 pregnant women were selected from the Maternal and Child Care
      Service Centre of Minhang District in Shanghai. Morning urinary iodine (UI) and
      iodine content of salt from the participants' home were measured, and UI
      concentration was adjusted by creatinine concentrations. Serum tri-iodothyronine,
      thyroxin, free tri-iodothyronine, free thyroxine and thyroid-stimulating hormone
      were tested in the second trimester of pregnancy by time-resolved
      fluoroimmunoassay. The median levels of UI in pregnant women were 156.3, 176.9
      and 175.1 MUg/g creatinine in the first, second and third trimesters of
      pregnancy, respectively. The prevalence of UI deficiency (UI < 150 MUg/g
      creatinine) was 48.3, 34.2 and 36.2% in the three trimesters of pregnancy,
      respectively. Factors that significantly influenced the UI levels include the
      following: iodine content of household salt; age; occupation; multivitamin
      supplement with iodine; seaweed intakes. Furthermore, UI and iodine content of
      salt were moderately correlated (r 0.406, P < 0.001). In addition, there was no
      significant association between UI and thyroid hormone levels. The present study
      showed a high prevalence of UI deficiency in pregnant women in Shanghai,
      especially during the first trimester of pregnancy. Both iodine content of
      household salt and multivitamin supplement with iodine are the main determinants
      of UI levels in Shanghai.

PMID- 25851150
TI  - Effects of phosphate limitation on soluble microbial products and microbial
      community structure in semi-continuous Synechocystis-based photobioreactors.
AB  - All bacteria release organic compounds called soluble microbial products (SMP) as
      a part of their normal metabolism. In photobioreactor (PBR) settings, SMP
      produced by cyanobacteria represent a major pool of carbon and electrons
      available to heterotrophic bacteria. Thus, SMP in PBRs are a major driver for the
      growth of heterotrophic bacteria, and understanding the distribution of SMP in
      PBRs is an important step toward proper management of PBR microbial communities.
      Here, we analyzed the SMP and microbial communities in two Synechocystis sp.
      PCC6803-based PBRs. The first PBR (PBRP0) became phosphate limited after several
      days of operation, while the second PBR (PBRP+) did not have phosphate
      limitation. Heterotrophic bacteria were detected in both PBRs, but PBRP0 had a
      much higher proportion of heterotrophic bacteria than PBRP+. Furthermore, PBRP+
      had greater biomass production and lower SMP production per unit biomass than
      PBRP0. Carbohydrates that were most likely derived from hydrolysis of
      extracellular polymeric substances (EPS) dominated the SMP in PBRP0, while
      products resulting from cell lysis or decay dominated the SMP in PBRP+. Together,
      our data support that maintaining phosphate availability in Synechocystis-based
      PBRs is important for managing SMP and, thus, the heterotrophic community.

PMID- 25851151
TI  - High arterial ligation and risk of anastomotic leakage in anterior resection for
      rectal cancer in patients with increased cardiovascular risk.
AB  - AIM: Controversy still exists as to whether division of the inferior mesenteric
      artery close to the aorta influences the risk of anastomotic leakage after
      anterior resection for rectal cancer. This population-based study was carried out
      to evaluate the independent association between high arterial ligation and
      anastomotic leakage in patients with increased cardiovascular risk. METHOD: All
      2673 cases of registered anterior resection for rectal cancer from 2007 to 2010
      were identified from the Swedish Colorectal Cancer Registry and cross-referenced
      with the Prescribed Drugs Registry, rendering a cohort of all patients with
      increased cardiovascular risk. Operative charts and registered data were reviewed
      for 722 patients. The association between high tie and anastomotic leakage, as
      quantified by ORs and 95% CIs, was evaluated in a logistic regression model, with
      adjustment for confounding, including assessment of interaction. RESULTS:
      Symptomatic anastomotic leakage occurred in 12.3% (41/334) of patients in the
      high tie group and in 10.6% (41/388) in the low tie group. The use of high tie
      was not independently associated with a higher risk of anastomotic leakage (OR =
      1.05; 95% CI: 0.61-1.84). In a post-hoc analysis, patients with a history of
      manifest cardiovascular disease and American Society of Anesthesiologists (ASA)
      score III-IV seemed to be at greater risk (OR = 3.66; 95% CI: 1.04-12.85).
      CONCLUSION: In the present population-based, observational setting, high tie was
      not independently associated with an increased risk of symptomatic anastomotic
      leakage after anterior resection for rectal cancer. However, this conclusion may
      not hold for patients with severe cardiovascular disease.

PMID- 25851152
TI  - The importance of communicating uncertainties in forecasts: overestimating the
      risks from winter storm Juno.

PMID- 25851154
TI  - Authors' reply to Wardlaw and Berge.

PMID- 25851156
TI  - Adult-type rhabdomyoma of the cervical esophagus.

PMID- 25851155
TI  - The change in nasal inflammatory markers after intranasal challenges with
      particulate chitin and lipopolysaccharide: a randomized, double-blind, placebo
      controlled, crossover study with a positive control.
AB  - BACKGROUND: We investigated the effect of chitin on the inflammation and immune
      modulation of the nasal mucosa. This compound was compared to placebo and as a
      positive control we used lipopolysaccharide (LPS). METHODS: Fourteen healthy
      nonsmoking volunteers 22 to 28 years of age were included. All persons underwent
      exposure to chitin microparticles (CP) and placebo in a randomized double-blinded
      fashion. In a last session we used LPS from Enterobacter agglomerans in a single
      blinded fashion. There were 2 weeks between each session. The outcome measures
      were Total Nasal Symptom Score (TNSS) and nasal lavage for cytokines and cells at
      0, 3, 4, 8 hours. RESULTS: We showed that CP was only weakly inflammatory
      compared to LPS. In contrast to the LPS response, we did however show an immune
      regulatory effect of CP on enhanced interleukin (IL)-4 and IL-6 responses known
      to downregulate T helper 2 (Th2) responses, indicating a potential beneficial
      effect of CP for the regulation of the allergic Th2 immune response. CONCLUSION:
      This study also shows that CP is well tolerated in healthy volunteers, and that
      does not induce significantly more symptoms compared to placebo. In fact there is
      a tendency for CP instillation to induce less rhinorrhoea compared to placebo.

PMID- 25851157
TI  - Successful extraction of a carelessly impacted bile duct stone using
      sphincterotome.

PMID- 25851158
TI  - Improvement in the visibility of colorectal polyps by using blue laser imaging
      (with video).
AB  - BACKGROUND: Fujifilm developed blue laser imaging (BLI) via a laser light source
      with a narrow-band light observation function. It has a brighter BLI bright mode
      for tumor detection. OBJECTIVE: To investigate whether the BLI bright mode can
      improve the visibility of colorectal polyps compared with white light (WL).
      DESIGN: We studied 100 colorectal polyps (protruding, 42; flat, 58; size, 2-20
      mm) and recorded videos of the polyps by using the BLI bright mode and WL at
      Kyoto Prefectural University of Medicine and Fukuoka Chikushi University
      Hospital. The videos were evaluated by 4 expert endoscopists and 4 nonexperts.
      Each endoscopist evaluated the videos in a randomized order. Each polyp was
      assigned a visibility score from 4 (excellent visibility) to 1 (poor visibility).
      SETTING: Japanese academic units. MAIN OUTCOME MEASUREMENTS: The visibility
      scores in each mode and their relationship to the clinical characteristics were
      analyzed. RESULTS: The mean visibility scores of the BLI bright mode were
      significantly higher than those of WL for both experts and nonexperts (experts,
      3.10 +/- 0.95 vs 2.90 +/- 1.09; P = .00013; nonexperts, 3.04 +/- 0.94 vs 2.78 +/-
      1.03; P < .0001). For all nonexperts, the visibility scores of the BLI bright
      mode were significantly higher than those of WL; however, these scores were
      significantly higher in only 2 experts. For experts, the mean visibility scores
      of the BLI bright mode was significantly higher than those of WL for flat polyps,
      neoplastic polyps, and polyps located on the left side of the colon and the
      rectum. LIMITATIONS: Small sample size and review of videos. CONCLUSIONS: Our
      study showed that polyps were more easily visible with the BLI bright mode
      compared with WL. ( CLINICAL TRIAL REGISTRATION NUMBER: UMIN000013770.).

PMID- 25851160
TI  - Recurrent acute pancreatitis secondary to Ascaris lumbricoides.

PMID- 25851159
TI  - Practice patterns of sedation for colonoscopy.
AB  - BACKGROUND: Sedative and analgesic medications have been used routinely for
      decades to provide patient comfort, reduce procedure time, and improve
      examination quality during colonoscopy. OBJECTIVE: To evaluate trends of sedation
      during colonoscopy in the United States. SETTING: Endoscopic data repository of
      U.S. gastroenterology practices (Clinical Outcomes Research Initiative, CORI
      database from 2000 until 2013). PATIENTS: The study population was made up of
      patients undergoing a total of 1,385,436 colonoscopies. INTERVENTIONS:
      Colonoscopy without any intervention or with mucosal biopsy, polypectomy, various
      means of hemostasis, luminal dilation, stent placement, or ablation. MAIN OUTCOME
      MEASUREMENTS: Dose of midazolam, diazepam, fentanyl, meperidine, diphenhydramine,
      promethazine, and propofol used for sedation during colonoscopy. RESULTS: During
      the past 14 years, midazolam, fentanyl, and propofol have become the most
      commonly used sedatives for colonoscopy. Except for benzodiazepines, which were
      dosed higher in women than men, equal doses of sedation were given to female and
      male patients. White patients were given higher doses than other ethnic groups
      undergoing sedation for colonoscopy. Except for histamine-1 receptor antagonists,
      all sedative medications were given at lower doses to patients with increasing
      age. The dose of sedatives was higher in colonoscopies associated with procedural
      interventions or of long duration. LIMITATIONS: Potential for incomplete or
      incorrect documentation in the database. CONCLUSION: The findings reflect on
      colonoscopy practice in the United States during the last 14 years and provide an
      incentive for future research on how sex and ethnicity influence sedation
      practices.

PMID- 25851161
TI  - Recurrence rates after EMR of large sessile serrated polyps.
AB  - BACKGROUND: Little is known regarding the recurrence rate after EMR of large
      (>=20 mm) sessile serrated adenoma/polyps (SSA/Ps). OBJECTIVE: To compare the
      recurrence rate among SSA/Ps and conventional adenomas in patients referred to a
      specialty practice for EMR. DESIGN: Retrospective cohort study. SETTING: Academic
      hospital and a satellite surgery center. PATIENTS: A total of 362 consecutive
      patients referred for resection of large (>=20 mm) polyps in the colorectum.
      INTERVENTIONS: All EMRs were performed with a submucosal contrast agent. All
      subjects had a follow-up surveillance examination (inspection and biopsy of the
      EMR) at our center. MAIN OUTCOME MEASUREMENTS: Rates of residual polyp at follow
      up examination. RESULTS: Residual polyp was identified among 8.7% of SSA/Ps
      compared with 11.1% for conventional adenomas (P = .8). LIMITATIONS:
      Retrospective design, procedures performed by a single experienced endoscopist,
      low number of serrated lesions. CONCLUSIONS: The rate of recurrence after EMR of
      SSA/Ps is similar to the rate after EMR of conventional adenomas.

PMID- 25851163
TI  - The impact of commissioning for rhinosinusitis in England.
AB  - OBJECTIVES: To assess the compliance of clinical commissioning groups (CCGs) in
      England with the ENT-UK rhinosinusitis commissioning guide produced in
      collaboration with the Royal College of Surgeons England and the National
      Institute of Clinical Excellence. We also aimed to assess the ease of
      accessibility of data from CCGs. DESIGN: Audit of compliance of English CCGs with
      the ENT-UK rhinosinusitis commissioning guide. SETTING: CCGs in England
      PARTICIPANTS: A total of 58 of the 221 CCGs in England were included and chosen
      because they were the first CCGs authorised by NHS England, or alternately, the
      CCGs forecasted to have a deficit in their first year of operation. Their
      websites were reviewed; when information was not easily accessible, a freedom of
      information request was submitted to the relevant CCG. MAIN OUTCOME MEASURES:
      Compliance with commissioning guidelines for rhinosinusitis. RESULTS: Thirteen
      percent of CCGs had restrictive referral criteria in place, largely unrelated to
      published evidence-based guidance. The routine use of multiple courses of oral
      steroids, prescription of antibiotics, CT scanning within primary care, and
      delaying referral for a year, prior to referral to a specialist were recommended
      against published advice. CONCLUSIONS: Restricting access to surgery may
      contribute to poorer outcomes and a decrease in the patient's quality of life.
      This is against the NHS constitution and is open to legal challenge. We encourage
      all ENT surgeons to review policies of their local CCG and engage with
      commissioners to ensure that their patients have evidence-based care.

PMID- 25851162
TI  - Survival and clinical outcome after endoscopic duodenal stent placement for
      malignant gastric outlet obstruction: comparison of pancreatic cancer and
      nonpancreatic cancer.
AB  - BACKGROUND: Data on endoscopic stenting of malignant gastric outlet obstruction
      (GOO) are based on studies predominantly involving patients with pancreatic
      adenocarcinoma. OBJECTIVE: To compare survival and clinical outcome after stent
      placement for GOO due to pancreatic cancer compared with nonpancreatic cancer.
      DESIGN: Retrospective study. SETTING: Single tertiary hospital. PATIENTS: A total
      of 292 patients with malignant GOO. INTERVENTION: Stent placement. MAIN OUTCOME
      MEASUREMENTS: Post-stent placement survival and clinical outcome. RESULTS: In 196
      patients with pancreatic cancer and 96 with nonpancreatic cancer, median post
      stent placement survival was similar (2.7 months in pancreatic cancer vs 2.4
      months in nonpancreatic cancer). Overall survival was shorter in patients with
      pancreatic cancer (13.7 vs 17.1 months; P = .004). Clinical success rates at 2
      months (71% vs 91%) and reintervention rates (30% vs 23%) were comparable. Post
      stent placement chemotherapy and the absence of distant metastasis were
      associated with better post-stent placement survival in both groups (pancreatic
      cancer: chemotherapy vs no chemotherapy, 5.4 vs 1.5 months, P < .0001; metastasis
      vs no metastasis, 1.8 vs 4.6, P = .005; nonpancreatic cancer: chemotherapy vs no
      chemotherapy, 9.2 vs 1.8, P = .001; metastasis vs no metastasis, 2.1 vs 6.1, P =
      .009). LIMITATIONS: Retrospective study. CONCLUSIONS: In this large series of
      patients undergoing stent placement for malignant GOO in North America, we
      observed no difference in post-stent placement survival despite better overall
      survival in patients with nonpancreatic cancer. GOO is a marker for poor survival
      in malignancy, regardless of the type. Chemotherapy and the absence of distant
      metastasis were associated with better post-stent placement survival in both
      groups.

PMID- 25851164
TI  - Chronic probable PTSD in police responders in the world trade center health
      registry ten to eleven years after 9/11.
AB  - BACKGROUND: Police enrolled in the World Trade Center Health Registry (WTCHR)
      demonstrated increased probable posttraumatic stress disorder (PTSD) after the
      terrorist attack of 9/11/2001. METHODS: Police enrollees without pre-9/11 PTSD
      were studied. Probable PTSD was assessed by Posttraumatic Stress Check List
      (PCL). Risk factors for chronic, new onset or resolved PTSD were assessed using
      multinomial logistic regression. RESULTS: Half of police with probable PTSD in
      2003-2007 continued to have probable PTSD in 2011-2012. Women had higher
      prevalence of PTSD than men (15.5% vs. 10.3%, P = 0.008). Risk factors for
      chronic PTSD included decreased social support, unemployment, 2+ life stressors
      in last 12 months, 2+ life-threatening events since 9/11, 2+ injuries during the
      9/11 attacks, and unmet mental health needs. CONCLUSION: Police responders to the
      WTC attacks continue to bear a high mental health burden. Improved early access
      to mental health treatment for police exposed to disasters may be needed.

PMID- 25851165
TI  - Heat-related symptoms in sugarcane harvesters.
AB  - BACKGROUND: Exposure to heat stress is a documented risk for Central American
      sugarcane harvesters. However, little is known about heat-related illness in this
      population. METHODS: This study examined the frequency of heat-related health
      effects among harvesters (n = 106) exposed to occupational heat stress compared
      to non-harvesters (n = 63). Chi-square test and gamma statistic were used to
      evaluate differences in self-reported symptoms and trends over heat exposure
      categories. RESULTS: Heat and dehydration symptoms (headache, tachycardia, muscle
      cramps, fever, nausea, difficulty breathing, dizziness, swelling of hands/feet,
      and dysuria) were experienced at least once per week significantly more
      frequently among harvesters. Percentages of workers reporting heat and
      dehydration symptoms increased in accordance with increasing heat exposure
      categories. CONCLUSIONS: A large percentage of harvesters are experiencing heat
      illness throughout the harvest demonstrating an urgent need for improved
      workplace practices, particularly in light of climate change and the epidemic of
      chronic kidney disease prevalent in this population.

PMID- 25851167
TI  - Isolation and characterization of bacterial strains with the ability to utilize
      high concentrations of levulinic acid, a platform chemical from inedible biomass.
AB  - Nineteen levulinic acid (LA)-utilizing bacteria were isolated from environmental
      samples. Following examination of the use of 80 g/L LA by some isolated strains,
      Brevibacterium epidermidis LA39-2 consumed 62.6 g/L LA following 8 days
      incubation. The strain also utilized both 90 and 100 g/L LA, with consumption
      ratio of 84.3 and 53.3%, respectively, after 10 days incubation.

PMID- 25851166
TI  - Case cluster of pneumoconiosis at a coal slag processing facility.
AB  - BACKGROUND: During an inspection by the Occupational Safety and Health
      Administration (OSHA) of a small coal slag processing plant with 12 current
      workers, four cases of pneumoconiosis were identified among former workers.
      METHODS: The OSHA investigation consisted of industrial hygiene sampling, a
      review of medical records, and case interviews. RESULTS: Some personal sampling
      measurements exceeded the OSHA Permissible Exposure Limit (PEL) for total dust
      exposures of 15 mg/m(3), and the measured respirable silica exposure of 0.043
      mg/m(3), although below OSHA's current PEL for respirable dust containing silica,
      was above the American Conference of Governmental Industrial Hygienists'
      Threshold Limit Value (TLV). Chest x-rays for all four workers identified small
      opacities consistent with pneumoconiosis. CONCLUSION: This is the first known
      report of lung disease in workers processing coal slag and raises concerns for
      workers exposed to coal slag dust.

PMID- 25851168
TI  - Quantitative 3D-KPFM imaging with simultaneous electrostatic force and force
      gradient detection.
AB  - Kelvin probe force microscopy (KPFM) is a powerful characterization technique for
      imaging local electrochemical and electrostatic potential distributions and has
      been applied across a broad range of materials and devices. Proper interpretation
      of the local KPFM data can be complicated, however, by convolution of the true
      surface potential under the tip with additional contributions due to long range
      capacitive coupling between the probe (e.g. cantilever, cone, tip apex) and the
      sample under test. In this work, band excitation (BE)-KPFM is used to negate such
      effects. In contrast to traditional single frequency KPFM, multifrequency BE-KPFM
      is shown to afford dual sensitivity to both the electrostatic force and the force
      gradient detection, analogous to simultaneous amplitude modulated and frequency
      modulated KPFM imaging. BE-KPFM is demonstrated on a Pt/Au/SiO(x) test structure
      and electrostatic force gradient detection is found to lead to an improved
      lateral resolution compared to electrostatic force detection. Finally, a 3D-KPFM
      imaging technique is developed. Force volume (FV) BE-KPFM allows the tip-sample
      distance dependence of the electrostatic interactions (force and force gradient)
      to be recorded at each point across the sample surface. As such, FVBE-KPFM
      provides a much needed pathway towards complete tip-sample capacitive de
      convolution in KPFM measurements and will enable quantitative surface potential
      measurements with nanoscale resolution.

PMID- 25851169
TI  - Hypoxia down-regulates expression of secretory leukocyte protease inhibitor in
      bronchial epithelial cells via TGF-beta1.
AB  - BACKGROUND: Secretory leukocyte protease inhibitor (SLPI) is a protein with anti
      protease and antimicrobial properties that is constitutively secreted from the
      airway epithelium. The importance of maintaining a balance between proteases and
      anti-proteases, and robust innate defence mechanisms in the airways, is
      exemplified by inflammatory lung conditions such as chronic obstructive pulmonary
      disease (COPD) and cystic fibrosis (CF). Both conditions present with a high
      protease burden in the airways which leads to tissue destruction. These patients
      also have an impaired innate immune system in the lungs with bacterial
      colonization and frequent airway infections. Moreover, both diseases are
      associated with airway hypoxia due to inflammation and mucus plugs. The aim of
      the present study was to investigate the role of hypoxia on SLPI production from
      the airway epithelium. METHODS: Primary human bronchial epithelial cells were
      grown in sub-immersed cultures or as differentiated epithelium in air liquid
      interface cultures. Cells were incubated at 21% O2 (normoxia) or 1% O2 (hypoxia),
      and the release of SLPI was analysed with ELISA. RT-PCR was used to study the
      expression of SLPI and transforming growth factor beta1 (TGF-beta1). RESULTS:
      Hypoxia decreased the constitutive production of SLPI by bronchial epithelial
      cells. The multifunctional cytokine TGF-beta1, which is known to affect SLPI
      expression, showed increased expression in hypoxic bronchial epithelial cells.
      When bronchial epithelial cells were exposed to exogenous TGF-beta1 during
      normoxia, the SLPI production was down-regulated. Addition of TGF-beta1
      neutralizing antibodies partially restored SLPI production during hypoxia,
      showing that TGF-beta1 is an important regulator of SLPI during hypoxic
      conditions. CONCLUSIONS: The mechanism described here adds to our knowledge of
      the pathogenesis of severe pulmonary diseases associated with hypoxia, e.g. COPD
      and CF. The hypoxic down-regulation of SLPI may help explain the protease/anti
      protease imbalance associated with these conditions and vulnerability to airway
      infections. Furthermore, it provides an interesting target for the treatment and
      prevention of exacerbation in these patients.

PMID- 25851170
TI  - Right Ventricular Enlargement In Utero: Is It Coarctation?
AB  - Antenatal diagnosis of right heart enlargement has a wide spectrum of
      differential diagnosis from maternal, placental and fetal causes, and outcomes of
      all are not known. Coarctation of the aorta is in the differential diagnosis of
      right heart enlargement. In our study, we focused to measure multiple cardiac
      dimensions in fetuses with right heart enlargement to identify the fetus with
      coarctation of the aorta utilizing echocardiographic measurements. Ten
      cardiovascular dimensions were measured from fetal studies between 20- and 34
      week gestation, and six were measured on postnatal echocardiograms. Z-scores for
      the cardiac dimensions were calculated, and each variable for fetuses and infants
      was tested using a two-sample t test between patients with and without
      coarctation. We excluded fetuses with TAPVR, Shone complex, interrupted aortic
      arch, Ebstein anomaly or HLHS. Of the 31 fetuses with in utero right heart
      enlargement, 11 had coarctation postnatally and 20 did not have coarctation. We
      compared the fetal and newborn cardiac dimensions between the groups. The mean
      fetal carotid-subclavian index (CS Index) was 0.7 mm with coarctation compared
      with 1.1 mm without coarctation (p < 0.0001). The mean difference in diameter z
      scores for fetal aortic isthmus (p < 0.0001), mitral valve (<0.001) and aortic
      valve (p < 0.009) was also significantly different. Similar significant
      differences were noted postnatally in the diameters of the cardiac dimensions
      between the coarctation and no-coarctation group: CS index (p < 0.0001), aortic
      isthmus (p < 0.0002) and aortic valve annulus (p < 0.007). A spectrum of
      diagnoses was found postnatally in fetuses with right heart enlargement,
      including a normal heart. The likelihood of identifying fetuses with coarctation
      of the aorta and planning for postnatal management can be refined by noninvasive
      screening measurements. A smaller CS index and smaller diameters of the aortic
      isthmus, mitral valve and aortic valve were significantly associated prenatally
      (p < 0.05) with coarctation of the aorta versus without coarctation and might be
      useful in prenatally diagnosing coarctation of the aorta. Postnatally, these
      measurements are reproducible. This is the first study utilizing these specific
      measurements to diagnose coarctation prenatally.

PMID- 25851171
TI  - Valproate in the treatment of epilepsy in girls and women of childbearing
      potential.
AB  - This document provides guidance on the use of valproate in girls and women of
      childbearing age from a joint Task Force of the Commission on European Affairs of
      the International League Against Epilepsy (CEA-ILAE) and the European Academy of
      Neurology (EAN), following strengthened warnings from the Coordination Group for
      Mutual Recognition and Decentralised Procedures-Human (CMDh) of the European
      Medicines Agency (EMA), which highlight the risk of malformations and
      developmental problems in infants who are exposed to valproate in the womb. To
      produce these recommendations, the Task Force has considered teratogenic risks
      associated with use of valproate and treatment alternatives, the importance of
      seizure control and of patient and fetal risks with seizures, and the
      effectiveness of valproate and treatment alternatives in the treatment of
      different epilepsies. The Task Force's recommendations include the following: (1)
      Where possible, valproate should be avoided in women of childbearing potential.
      (2) The choice of treatment for girls and women of childbearing potential should
      be based on a shared decision between clinician and patient, and where
      appropriate, the patient's representatives. Discussions should include a careful
      risk-benefit assessment of reasonable treatment options for the patient's seizure
      or epilepsy type. (3) For seizure (or epilepsy) types where valproate is the most
      effective treatment, the risks and benefits of valproate and other treatment
      alternatives should be discussed. (4) Valproate should not be prescribed as a
      first-line treatment for focal epilepsy. (5) Valproate may be offered as a first
      line treatment for epilepsy syndromes where it is the most effective treatment,
      including idiopathic (genetic) generalized syndromes associated with tonic-clonic
      seizures. (6) Valproate may be offered as a first-line treatment in situations
      where pregnancy is highly unlikely (e.g., significant intellectual or physical
      disability). (7) Women and girls taking valproate require regular follow-up for
      ongoing consideration of the most appropriate treatment regimen.

PMID- 25851172
TI  - Social cognitive deficits and biases in maltreated adolescents in U.K. out-of
      home care: Relation to disinhibited attachment disorder and psychopathology.
AB  - Children entering out-of-home (OoH) care have often experienced multiple forms of
      maltreatment and are at risk of psychiatric disorder and poor long-term outcome.
      Recent evidence shows high rates of disinhibited attachment disorder (DAD) among
      maltreated adolescents in U.K. OoH care (Kay & Green, 2013). This study aimed to
      further understand the mechanisms of outcome in this group through investigation
      of social cognitive functioning. Patterns of theory of mind (ToM) and social
      information processing were assessed alongside DAD behavior and psychopathology
      in 63 adolescents in U.K. OoH care (mean age = 176 months, SD = 22; 48% male; 89%
      White British) and 69 low-risk comparison adolescents (mean age = 171 months, SD
      = 17; 46% male; 87% White British). Compared to low risk, OoH adolescents showed
      a hostile attribution bias and ToM deficit, but this was confounded by language
      ability. ToM was associated with reduced hostile attribution and responding
      biases and increased social competence, which was further associated with lower
      levels of externalizing psychopathology. There was no association between social
      cognition and core features of DAD. Social cognitive deficits and biases may play
      a role in the high rates of externalizing psychopathology and relationship
      functioning difficulties in maltreated samples. Future research should assess
      alternative cognitive mechanisms for DAD.

PMID- 25851174
TI  - Bayesian hierarchical regression on clearance rates in the presence of "lag" and
      "tail" phases with an application to malaria parasites.
AB  - We present a principled technique for estimating the effect of covariates on
      malaria parasite clearance rates in the presence of "lag" and "tail" phases
      through the use of a Bayesian hierarchical linear model. The hierarchical
      approach enables us to appropriately incorporate the uncertainty in both
      estimating clearance rates in patients and assessing the potential impact of
      covariates on these rates into the posterior intervals generated for the
      parameters associated with each covariate. Furthermore, it permits us to
      incorporate information about individuals for whom there exists only one
      observation time before censoring, which alleviates a systematic bias affecting
      inference when these individuals are excluded. We use a changepoint model to
      account for both lag and tail phases, and hence base our estimation of the
      parasite clearance rate only on observations within the decay phase. The Bayesian
      approach allows us to treat the delineation between lag, decay, and tail phases
      within an individual's clearance profile as themselves being random variables,
      thus taking into account the additional uncertainty of boundaries between phases.
      We compare our method to existing methodology used in the antimalarial research
      community through a simulation study and show that it possesses desirable
      frequentist properties for conducting inference. We use our methodology to
      measure the impact of several covariates on Plasmodium falciparum clearance rate
      data collected in 2009 and 2010. Though our method was developed with this
      application in mind, it can be easily applied to any biological system exhibiting
      these hindrances to estimation. 

PMID- 25851175
TI  - High resolution CT study of the chorda tympani nerve and normal anatomical
      variation.
AB  - OBJECTIVE: The aim of this study was to define the normal anatomical variation of
      the course of the CTN through the mastoid temporal bone on high resolution CT
      (HRCT). MATERIALS AND METHODS: Retrospective review of 27 consecutive normal HRCT
      bilateral temporal bones (n = 54, 14 males and 13 females, mean age 41 years)
      reconstructed at 0.4-mm slice thickness specifically measuring (1) origin of CTN
      from the posterior genu of the facial nerve (CNVII) and (2) the lateral-most
      position of the CTN from the mastoid segment of CNVII. RESULTS: The mean distance
      of the CTN origin from the mastoid segment of CNVII was 11.5 mm (standard
      deviation, SD = 3.2, 95% CI 10.7-12.3) with no statistically significant
      difference between the left and right side observed (p = 0.08). The most lateral
      distance of the CTN from CNVII was a mean of 1.3 mm (SD = 0.6, 95% CI 1.2-1.7),
      range 0-2.5 mm and again no statistical significance between contralateral sides
      was observed (p = 0.11). These measurements demonstrated an excellent level of
      agreement between observers as assessed by intraclass correlation calculation.
      CONCLUSIONS: Reproducible measurements demonstrate variability of the CTN in both
      its origin from the mastoid segment of CNVII and its lateral-most course. Precise
      description of the course of the CTN with HRCT may be useful for planning of
      otologic surgery and limiting inadvertent nerve injury.

PMID- 25851173
TI  - Poly(ADP-ribose) polymerase-13 and RNA regulation in immunity and cancer.
AB  - Post-transcriptional regulation of RNA is an important mechanism for activating
      and resolving cellular stress responses. Poly(ADP-ribose) polymerase-13 (PARP13),
      also known as ZC3HAV1 and zinc-finger antiviral protein (ZAP), is an RNA-binding
      protein that regulates the stability and translation of specific mRNAs, and
      modulates the miRNA silencing pathway to globally affect miRNA targets. These
      functions of PARP13 are important components of the cellular response to stress.
      In addition, the ability of PARP13 to restrict oncogenic viruses and to repress
      the prosurvival cytokine receptor tumor necrosis factor (TNF)-related apoptosis
      inducing ligand receptor 4 (TRAILR4) suggests that it can be protective against
      malignant transformation and cancer development. The relevance of PARP13 to human
      health and disease make it a promising therapeutic target. 

PMID- 25851176
TI  - Vestibular evoked myogenic potentials in pediatric patients with familial
      Mediterranean fever.
AB  - OBJECTIVES: We aimed to investigate whether the chronic autoinflammatory process
      in familial Mediterranean fever (FMF), which affects numerous systems, results in
      vestibular dysfunction in pediatric patients being followed up for diagnosis of
      FMF using VEMP recordings. METHODS: 30 patients (60 ears) diagnosed with FMF and
      20 (40 ears) healthy volunteers were included in the study. Following routine
      ear, nose, and throat examination, transient-evoked otoacoustic emissions (TEOAE)
      and vestibular-evoked myogenic potential (VEMP) tests were performed. RESULTS: A
      total of 30 FMF pediatric patients (13 male, 17 female) and 20 controls (8 male,
      12 female) were included in the study. The mean age of FMF patients was 12.13 +/-
      2.88 years, while that of the controls was 12.90 +/- 2.80 years. All of the
      otoacoustic emission results of the patient and control groups were "pass VEMP
      recordings received in both ears of patients with FMF (60 ears) and both ears of
      controls (40 ears). There was no statistically significant difference for
      latencies or amplitudes for either patients or controls (p > 0.05). CONCLUSION:
      In order to research the effect of FMF on vestibular functions, we measured VEMP.
      However, we did not detect alterations of VEMP in FMF patients.

PMID- 25851177
TI  - Residual lifetime and 10 year absolute risks of osteoporotic fractures in Chinese
      men and women.
AB  - OBJECTIVE: To determine the residual lifetime and 10 year absolute risks of
      osteoporotic fractures in Chinese men and women. METHODS: A validated state
      transition microsimulation model was used. Microsimulation and probabilistic
      sensitivity analyses were performed to address the uncertainties in the model.
      All parameters including fracture incidence rates and mortality rates were
      retrieved from published literature. Simulated subjects were run through the
      model until they died to estimate the residual lifetime fracture risks. A 10 year
      time horizon was used to determine the 10 year fracture risks. We estimated the
      risk of only the first osteoporotic fracture during the simulation time horizon.
      RESULTS: The residual lifetime and 10 year risks of having the first osteoporotic
      (hip, clinical vertebral or wrist) fracture for Chinese women aged 50 years were
      40.9% (95% CI: 38.3-44.0%) and 8.2% (95% CI: 6.8-9.3%) respectively. For men, the
      residual lifetime and 10 year fracture risks were 8.7% (95% CI: 7.5-9.8%) and
      1.2% (95% CI: 0.8-1.7%) respectively. The residual lifetime fracture risks
      declined with age, whilst the 10 year fracture risks increased with age until the
      short-term mortality risks outstripped the fracture risks. Residual lifetime and
      10 year clinical vertebral fracture risks were higher than those of hip and wrist
      fractures in both sexes. CONCLUSIONS: More than one third of the Chinese women
      and approximately one tenth of the Chinese men aged 50 years are expected to
      sustain a major osteoporotic fracture in their remaining lifetimes. Due to
      increased fracture risks and a rapidly ageing population, osteoporosis will
      present a great challenge to the Chinese healthcare system. LIMITATIONS: While
      national data was used wherever possible, regional Chinese hip and clinical
      vertebral fracture incidence rates were used, wrist fracture rates were taken
      from a Norwegian study and calibrated to the Chinese population. Other fracture
      sites like tibia, humerus, ribs and pelvis were not included in the analysis,
      thus these risks are likely to be underestimates. Fracture risk factors other
      than age and sex were not included in the model. Point estimates were used for
      fracture incidence rates, osteoporosis prevalence and mortality rates for the
      general population.

PMID- 25851178
TI  - Anticonvulsant and Sedative Effects of Eudesmin isolated from Acorus tatarinowii
      on mice and rats.
AB  - This paper was designed to investigate anticonvulsant and sedative effects of
      eudesmin isolated from Acorus tatarinowii. The eudesmin (5, 10, and 20 mg/kg) was
      administered intraperitoneally (i.p.). The maximal electroshock test (MES) and
      pentylenetertrazole (PTZ)-induced seizures in male mice were used to evaluate
      anticonvulsant activities of eudesmin, and sedative effects of eudesmin were
      evaluated by pentobarbital sodium-induced sleeping time (PST) and locomotor
      activity in mice. Finally, the mechanisms of eudesmin were investigated by
      determining contents of glutamic acid (Glu) and gamma-aminobutyric acid (GABA) in
      epileptic mice, and expressions of glutamate decarboxylase 65 (GAD65), GABAA ,
      Bcl-2, and caspase-3 in the brain of chronic epileptic rats. Results of MES and
      PTZ tests revealed that eudesmin possesses significant anticonvulsant effects,
      and the PST and locomotor activity tests demonstrated that eudesmin has
      significant sedative effects. Furthermore, our study revealed that after
      treatment with eudesmin, GABA contents increased, whereas Glu contents decreased,
      and ratio of Glu/GABA decreased. Our results also indicated that expressions of
      GAD65, GABAA, and Bcl-2 were up-regulated by treating with eudesmin, whereas the
      caspase-3 obviously was down-regulated. In conclusion, eudesmin has significant
      anticonvulsant and sedative effects, and the mechanism of eudesmin may be related
      to up-regulation of GABAA and GAD65 expressions, and anti-apoptosis of neuron the
      in brain.

PMID- 25851179
TI  - Sevoflurane exposure prevents diaphragmatic oxidative stress during mechanical
      ventilation but reduces force and affects protein metabolism even during
      spontaneous breathing in a rat model.
AB  - BACKGROUND: Ventilator-induced diaphragmatic dysfunction is associated with the
      generation of oxidative stress, enhanced proteolysis, autophagy and reduced
      protein synthesis in the diaphragm. Sevoflurane is a common operating room
      anesthetic and can be used in the intensive care medicine as well. Besides its
      anesthetic properties, its use in cardiac ischemia-reperfusion models can
      maintain protein synthesis and inhibit generation of reactive oxygen species, if
      used at the beginning of heart surgery. This study has been performed on the
      hypothesis that sevoflurane might protect against ventilator-induced
      diaphragmatic dysfunction by preventing the production of oxidative stress.
      METHODS: Four-month-old, male Sprague-Dawley rats sedated with sevoflurane
      (minimal alveolar concentration = 1) were either mechanically ventilated (MV) for
      12 hours (n = 8) or allowed to breathe spontaneously (SB) for 12 hours (n = 8).
      An acutely anesthetized group was used as a control (Con) group (n = 8). After
      euthanization, diaphragmatic contractile properties, fiber cross-sectional areas,
      proteolysis (calpain-1 and caspase-3), and oxidative stress (lipid peroxidation,
      protein oxidation) were examined. After testing for normality, 1-way or 2-way
      analysis of variance with the Dunnett post hoc test was used to test for
      significance. RESULTS: The diaphragm contractile force was similarly reduced at
      all stimulation frequencies in the SB and MV groups compared with controls.
      Markers of oxidative stress and fiber cross-sectional areas were unaltered
      between Con and SB/MV, respectively. The calcium-dependent proteases (calpain-1
      and caspase-3) were enhanced in the MV group. The p-AKT/AKT ratio and p
      FoxO1/FoxO1 ratio were significantly and similarly reduced after sevoflurane
      exposure in the SB and MV group compared with Con group. CONCLUSIONS: Exposure to
      sevoflurane did not induce oxidative stress. It led to reduction in diaphragmatic
      force. In the MV group, sevoflurane led to the activation of atrophy signaling
      pathways. These findings are of particular importance for clinical utilization in
      intensive care units and question its use, especially during the phases of SB.

PMID- 25851180
TI  - Gene Transfer of Glutamic Acid Decarboxylase 67 by Herpes Simplex Virus Vectors
      Suppresses Neuropathic Pain Induced by Human Immunodeficiency Virus gp120
      Combined with ddC in Rats.
AB  - BACKGROUND: Human immunodeficiency virus (HIV)-related painful sensory
      neuropathies primarily consist of the HIV infection-related distal sensory
      polyneuropathy and antiretroviral toxic neuropathies. Pharmacotherapy provides
      only partial relief of pain in patients with HIV/acquired immune deficiency
      syndrome because little is known about the exact neuropathological mechanisms for
      HIV-associated neuropathic pain (NP). Hypofunction of gamma-aminobutyric acid
      (GABA) GABAergic inhibitory mechanisms has been reported after peripheral nerve
      injury. In this study, we tested the hypothesis that HIV gp120 combined with
      antiretroviral therapy reduces spinal GABAergic inhibitory tone and that
      restoration of GABAergic inhibitory tone will reduce HIV-related NP in a rat
      model. METHODS: The application of recombinant HIV-1 envelope protein gp120 into
      the sciatic nerve plus systemic ddC (one antiretroviral drug) induced mechanical
      allodynia. The hind paws of rats were inoculated with replication-defective
      herpes simplex virus (HSV) vectors genetically encoding gad1 gene to express
      glutamic acid decarboxylase 67 (GAD67), an enzyme that catalyzes the
      decarboxylation of glutamate to GABA. Mechanical threshold was tested using von
      Frey filaments before and after treatments with the vectors. The expression of
      GAD67 in both the lumbar spinal cord and the L4-5 dorsal root ganglia was
      examined using western blots. The expression of mitochondrial superoxide in the
      spinal dorsal horn was examined using MitoSox imaging. The immunoreactivity of
      spinal GABA, pCREB, and pC/EBPbeta was tested using immunohistochemistry.
      RESULTS: In the gp120 with ddC-induced neuropathic pain model, GAD67 expression
      mediated by the HSV vector caused an elevation of mechanical threshold that was
      apparent on day 3 after vector inoculation. The antiallodynic effect of the
      single HSV vector inoculation expressing GAD67 lasted >28 days. The area under
      the time-effect curves in the HSV vector expressing GAD67 was increased compared
      with that in the control vectors (P = 0.0005). Intrathecal GABA-A/B agonists
      elevated mechanical threshold in the pain model. The HSV vectors expressing GAD67
      reversed the lowered GABA immunoreactivity in the spinal dorsal horn in the
      neuropathic rats. HSV vectors expressing GAD67 in the neuropathic rats reversed
      the increased signals of mitochondrial superoxide in the spinal dorsal horn. The
      vectors expressing GAD67 reversed the upregulated immunoreactivity expression of
      pCREB and pC/EBPbeta in the spinal dorsal horn in rats exhibiting NP.
      CONCLUSIONS: Based on our results, we suggest that GAD67 mediated by HSV vectors
      acting through the suppression of mitochondrial reactive oxygen species and
      transcriptional factors in the spinal cord decreases pain in the HIV-related
      neuropathic pain model, providing preclinical evidence for gene therapy
      applications in patients with HIV-related pain states.

PMID- 25851182
TI  - Hybrid imaging with 99mTc-WBC SPECT/CT to monitor the effect of therapy in
      diabetic foot osteomyelitis.
AB  - This study sought to assess the utility of monitoring response to treatment of
      diabetic foot osteomyelitis (DFO) with Tc-99m WBC-labelled single photon emission
      computed tomography (SPECT/CT) imaging. This is a retrospective cohort study of
      20 patients with DFO with sequential Tc-99m WBC-labelled SPECT/CT imaging.
      Radiologic findings of osteomyelitis were evaluated and imaging results were
      correlated with clinical outcomes subtracted from chart review. Successful
      treatment of osteomyelitis was defined by wound healing and/or lack of re
      admission for bone infection of the same site within 1 year. The sensitivity,
      specificity, positive predictive value and negative predictive value of SPECT/CT
      to determine osteomyelitis treatment remission were 90%, 56%, 69% and 83%,
      respectively. Tc-99m WBC-labelled SPECT/CT imaging may be useful to help
      determine treatment outcomes for DFO.

PMID- 25851181
TI  - Food preparation methods, drinking water source, and esophageal squamous cell
      carcinoma in the high-risk area of Golestan, Northeast Iran.
AB  - Cooking practices and water sources have been associated with an increased risk
      of cancer, mainly through exposure to carcinogens such as heterocyclic amines,
      polycyclic aromatic hydrocarbons, and nitrates. Using data from the Golestan case
      control study, carried out between 2003 and 2007 in a high-risk region for
      esophageal squamous cell carcinoma (ESCC), we sought to investigate the
      association between food preparation and drinking water sources and ESCC.
      Information on food preparation methods, sources of drinking water, and dietary
      habits was gathered from 300 cases and 571 controls matched individually for age,
      sex, and neighborhood using a structured questionnaire and a semiquantitative
      food frequency questionnaire. Multivariate conditional logistic regression was
      used to estimate odds ratios (OR) and 95% confidence intervals (CI) adjusted for
      potential confounders and other known risk factors including socioeconomic status
      and smoking. More than 95% of the participants reported eating meat, mostly red
      meat. Red meat consumption above the 75th percentile increased the odds of ESCC
      by 2.82-fold (95% CI: 1.21-6.57). Fish intake was associated with a significant
      68% decrease in ESCC odds (26%, 86%). Among meat eaters, ORs (95% CI) for frying
      meat (red or white) and fish were 3.34 (1.32-8.45) and 2.62 (1.24-5.5). Drinking
      unpiped water increased ESCC odds by 4.25 times (2.23-8.11). The OR for each 10
      year increase in the duration of drinking unpiped water was 1.47 (1.22-1.78). Our
      results suggest roles for red meat intake, drinking water source, and food
      preparation methods in ESCC, even after adjusting for a large number of potential
      confounders. 

PMID- 25851183
TI  - The relative importance of the domains of work functioning: evaluations of health
      impaired employees, healthy employees, and employers.
AB  - OBJECTIVE: To determine the relative importance of central work functioning
      domains and propose a method for composite weighted measurement of the concept
      "work functioning." METHODS: Health-impaired workers, healthy workers, and
      employers (n = 277) weighed work functioning domains by participating in a
      discrete choice experiment. A logistic regression model was tested to reveal the
      relative importance of the domains. RESULTS: The central domains are significant
      indicators of the work functioning of health-impaired workers. The domain with
      the highest relative importance is quality of work performance, followed by,
      respectively, recovery, quantity of work, and capacity to work. This pattern of
      results was observed in all subgroups. CONCLUSIONS: The central domains are
      relevant indicators of the work functioning of health-impaired workers.
      Researchers should consider the relative importance of the domains and use the
      proposed weighting procedure, when measuring work functioning.

PMID- 25851184
TI  - Well-being improvement in a midsize employer: changes in well-being,
      productivity, health risk, and perceived employer support after implementation of
      a well-being improvement strategy.
AB  - OBJECTIVE: To evaluate employee well-being change and associated change in
      productivity, health risk including biometrics, and workplace support over 2
      years after implementation of a well-being improvement strategy. METHODS: This
      was an employer case study evaluation of well-being, productivity (presenteeism,
      absenteeism, and job performance), health risk, and employer support across three
      employee assessment spanning 2 years. Employee well-being was compared with an
      independent sample of workers in the community. RESULTS: Well-being and job
      performance increased and presenteeism and health risk decreased significantly
      over the 2 years. Employee well-being started lower and increased to exceed
      community worker averages, approaching significance. Well-being improvement was
      associated with higher productivity across all measures. Increases in employer
      support for well-being were associated with improved well-being and productivity.
      CONCLUSIONS: This employer's well-being strategy, including a culture supporting
      well-being, was associated with improved health and productivity.

PMID- 25851185
TI  - Assessing work-asthma interaction with Amazon Mechanical Turk.
AB  - OBJECTIVES: To illustrate the utility of crowdsourcing for occupational health
      surveillance. METHODS: Amazon Mechanical Turk was used to recruit and obtain
      information from employed persons with asthma, who answered questions about work
      asthma interactions. RESULTS: Data collection from 60 subjects required only a
      few hours. Participants spent on average 7 minutes responding to seven questions
      (one optional) and used an average of 708 words. Work exacerbation, interference
      of asthma with work, and suggested workplace accommodation are frequent (83%
      reported at least one interaction). CONCLUSIONS: The full spectrum of work-asthma
      interactions should be considered. Modern crowdsourcing methods have considerable
      potential as occupational health surveillance tools because of their
      effectiveness; efficiency and financial viability are additional important
      advantages.

PMID- 25851186
TI  - Psychosocial working conditions and sickness absence in a general population: a
      cohort study of 21,834 workers in Norway (The HUNT Study).
AB  - OBJECTIVE: To examine the associations between psychosocial working conditions
      and sickness absence. METHODS: Data for 21,834 employed adults from the Nord
      Trondelag Health Study (HUNT) were linked to the sickness benefit register and
      sickness absence during 1 year after survey participation was analyzed with
      logistic regression. RESULTS: A one unit change on a 0 to 3 self-reported job
      demand scale was associated with a fully adjusted 24% and 25% increased odds of
      sickness absence in men and women, respectively. A one unit change on a 0 to 3
      scale for self-reported support at work was associated with a fully adjusted 13%
      and 17% reduced odds of sickness absence in men and women, respectively.
      CONCLUSIONS: The results of this study indicate that demands, and to some extent
      support, at work might influence sickness absence-also when adjusting for a
      detailed categorization of occupations.

PMID- 25851187
TI  - Marijuana in the workplace: guidance for occupational health professionals and
      employers: Joint Guidance Statement of the American Association of Occupational
      Health Nurses and the American College of Occupational and Environmental
      Medicine.

PMID- 25851190
TI  - Is there an association of circulatory hospitalizations independent of mining
      employment in coal-mining and non-coal-mining counties in west virginia?
AB  - OBJECTIVE: Exposures associated with coal mining activities, including diesel
      fuel exhaust, products used in coal processing, and heavy metals and other forms
      of particulate matter, may impact the health of nearby residents. We investigated
      the relationships between county-level circulatory hospitalization rates (CHRs)
      in coal and non-coal-mining communities of West Virginia, coal production, coal
      employment, and sociodemographic factors. METHODS: Direct age-adjusted CHRs were
      calculated using West Virginia hospitalizations from 2005 to 2009. Spatial
      regressions were conducted to explore associations between CHR and total,
      underground, and surface coal production. RESULTS: After adjustment, neither
      total, nor surface, nor underground coal production was significantly related to
      rate of hospitalization for circulatory disease. CONCLUSIONS: Our findings
      underscore the significant role sociodemographic and behavioral factors play in
      the health and well-being of coal mining communities.

PMID- 25851191
TI  - Biomarkers for lung epithelium injury in occupational hexavalent chromium-exposed
      workers.
AB  - OBJECTIVE: To evaluate whether Club (Clara) cell protein (CC16) and surfactant
      associated protein D (SP-D) can be used as biomarkers for lung injury caused by
      chromium exposure. METHODS: The concentrations of chromium in the air (CrA),
      chromium in the blood (CrB), lung function, CC16, SP-D, tumor necrosis factor
      alpha (TNF-alpha), and interleukin-6 (IL-6) were detected in 91 chromium-exposed
      workers and 38 controls. RESULTS: In chromium-exposed group, the levels of CrA,
      CrB, SP-D, TNF-alpha, and IL-6 were significantly higher, whereas forced
      expiratory volume in one second (FEV1), FEV1/FVC, maximal expiratory flow (MEF),
      maximum ventilation volume (MVV), CC16, and CC16/SP-D were lower. Negative
      correlations were shown between CC16, SP-D or CC16/SP-D, and CrB or inflammatory
      cytokines (TNF-alpha and IL-6). Positive relationships were shown between CC16 or
      CC16/SP-D with indicators of lung function. Tobacco smoking and chromium exposure
      had synergic effects on lung injury. CONCLUSIONS: CC16, as an immunosuppressive
      protein, and CC16/SP-D can be used as sensitive and noninvasive biomarkers for
      lung injury. Smoking should be banned in chromium workplaces.

PMID- 25851192
TI  - Platelet parameters evaluation in benzene-exposed participants: role of
      confounding factors.

PMID- 25851193
TI  - Risk factors for mortality in Down syndrome.
AB  - BACKGROUND: Down syndrome is a genetic condition that contributes to a
      significantly shorter life expectancy compared with the general population. We
      investigated the most common comorbidities in a population of acute hospital
      patients with Down syndrome and further explored what the most common risk
      factors for mortality are within this population. METHOD: From our database of
      one million patients admitted to National Health Service (NHS) Trusts in northern
      England, we identified 558 people who had Down syndrome. We compared this group
      with an age- and gender-matched control group of 5580 people. RESULTS: The most
      prevalent comorbid diseases within the Down's population were hypothyroidism
      (22.9%) and epilepsy (20.3%). However, the conditions that had the highest
      relative risks (RRs) in the Down's population were septal defects and dementia.
      Respiratory failure, dementia and pneumonia were the most significantly related
      comorbidities to mortality in the Down syndrome population. In the control
      population, respiratory failure, dementia and renal failure were the most
      significant disease contributors. When these contributors were analysed using
      multivariate analysis, heart failure, respiratory failure, pneumonia and epilepsy
      were the identified risk factors for in-hospital mortality in the Down syndrome
      population. Respiratory failure was the sole risk factor for mortality in the
      Down syndrome population [RR = 9.791 (1.6-59.9) P <= 0.05], when compared with
      the risk factors for mortality in the control population. CONCLUSIONS: There is
      significant medical morbidity in Down syndrome. This morbidity contributes to the
      lower life expectancy. Respiratory failure is a risk factor for mortality in Down
      syndrome. We need to thoroughly investigate people with Down syndrome to ensure
      any treatable illnesses are well managed.

PMID- 25851195
TI  - Malaria Control in Amerindian Communities of Venezuela : Strengthening Ecohealth
      Practice Throughout Conservation Science and Capability Approach.
AB  - Adaptive management and ecohealth frameworks were developed for malaria
      elimination in Amerindian riparian communities of Venezuela. These frameworks
      were developed as a strategy to capture, organize, and communicate connections
      among key factors related to local malaria complex systems. Important causal
      relationships between social, economic, and environmental stressors which are
      determinant of malaria were identified at different levels and assumptions that
      guide interventions are offered, based on available scientific knowledge and
      input from stakeholders. Drawing on our experience of action research committed
      to the health of Amerindian populations and conservation of areas with
      biodiversity value, the authors provide lessons to strengthen the practice of an
      ecohealth approach. First, conservation targets were considered as a way to
      achieve sustainable human well-being rather than as a consequence of well-being.
      Second, the effectiveness and sustainability of technical solutions generally
      proposed for malaria control depend largely on individual knowledge, attitudes,
      and practices. Hence, it is necessary to look at the real opportunities of
      choices that Amerindian people have for attaining a life without malaria, and
      therefore pay attention to local capabilities, needs, and freedom to choose. The
      ecohealth approach can benefit from the capability approach, and we explain why. 

PMID- 25851196
TI  - Decline of General Intelligence in Children Exposed to Manganese from Mining
      Contamination in Puyango River Basin, Southern Ecuador.
AB  - Based on ecosystem approaches to health (Ecohealth), this study sought to
      identify neurobehavioral disorders in children exposed to several levels of toxic
      metal pollution from gold mining in the Puyango River Basin, Southern Ecuador.
      Ninety-three children born or living in the study area participated in the study.
      A neurobehavioral test battery consisting of 12 tests assessing various functions
      of the nervous system was applied as well as a questionnaire regarding events of
      exposure of children's mothers to contaminants during perinatal period. Hair
      samples were taken from children to determine manganese concentrations.
      Descriptive and inferential statistics were applied in order to examine possible
      relationships between exposure events, hair manganese, and neurobehavioral
      disorders. Having controlled co-variables such as age and educational level, it
      was found that children with elevated levels of hair manganese (over 2 MUg/g) had
      poor performance in the test of general intelligence (Raven's Progressive Color
      Matrices Scale PCM). The Ecohealth approach helped to identify that children in
      the lower Puyango Basin with very elevated levels of manganese in the river water
      (970 ug/L) are the ones who have the highest levels of hair manganese and the
      worst performance in the intelligence test.

PMID- 25851197
TI  - Toward Operational Criteria for Ecosystem Approaches to Health.

PMID- 25851198
TI  - Charge transfer in MOH(H2O)(+) (M = Mn, Fe, Co, Ni, Cu, Zn) complexes revealed by
      vibrational spectroscopy of mass-selected ions.
AB  - Charge transfer between a metal and its ligand is fundamental for the structure
      and reactivity of a metal complex as it directly dictates the distribution of
      electron density within the complex. To better understand such charge transfer
      interactions, we studied the vibrational spectra of mass-selected MOH(H2O)(+) (M
      = Mn, Fe, Co, Ni, Cu, or Zn) complexes, acquired using cryogenic ion infrared
      predissociation spectroscopy. We find that there is a partial charge transfer
      from the hydroxide anion to the metal center for these first-row transition
      metals, the extent of which is in the order of Mn < Fe < Co < Ni < Cu > Zn,
      dictated by the 2nd ionization energy of the bare metal. This gradual change
      across the metal series points to the complexity in the electronic structures of
      these transition metal complexes. Interestingly, the hydroxide ligand in these
      complexes can serves as a sensitive in situ probe of this charge transfer. Its
      vibrational frequency varies by >150 cm(-1) for different metal species, and it
      is dependent on the electric field produced by the charged metal center. This
      dramatic vibrational Stark shift is further modulated by the charge present on
      the hydroxide itself, providing a well-defined relationship between the observed
      hydroxide frequency and the effective electric field. 

PMID- 25851199
TI  - Reperfusion Rates of Pulmonary Arteriovenous Malformations after Coil
      Embolization: Evaluation with Time-Resolved MR Angiography or Pulmonary
      Angiography.
AB  - PURPOSE: To assess reperfusion rates after coil embolization for pulmonary
      arteriovenous malformations (PAVMs) using time-resolved magnetic resonance (MR)
      angiography or pulmonary angiography. MATERIALS AND METHODS: Patients with PAVMs
      who underwent embolization and met the following inclusion criteria were
      included: (a) embolization was performed using bare or fibered platinum
      microcoils or both, (b) the complete cessation of flow was confirmed by digital
      subtraction angiography, and (c) follow-up examinations were conducted with time
      resolved MR angiography or pulmonary angiography. Coil embolization was performed
      in 16 patients with 24 untreated or reperfused PAVMs. Sac embolization was
      performed for 12 untreated PAVMs. Feeding artery embolization was performed as
      primary embolization in each of the 12 reperfused PAVMs. Five PAVMs were treated
      2 to 4 times because of reperfusion. The study included 32 coil embolizations.
      Follow-up images were reviewed, and reperfusion rates were assessed. The
      relationships between reperfusion and the location of PAVM, size of PAVM (feeding
      artery and venous sac), coils (number and total length), timing of embolization
      (primary or repeat embolization), and types of coils used (with or without
      fibered coils) were examined. RESULTS: Reperfusion rates at 3, 6, 12, and 24
      months were 8%, 27%, 36%, and 49%, respectively, for the 12 untreated PAVMs
      (primary embolization) and 50%, 50%, 92%, and 100%, respectively, for the 12
      reperfused PAVMs (repeat embolization) (P = .0062). No significant differences
      were observed in the other parameters measured. CONCLUSIONS: When evaluated with
      time-resolved MR angiography or pulmonary angiography, reperfusion rates after
      coil embolization for PAVM were considerably high, particularly with repeat
      embolization.

PMID- 25851200
TI  - Endovascular management of early lung transplant-related anastomotic pulmonary
      artery stenosis.
AB  - PURPOSE: To report the safety and short-term efficacy of endovascular
      interventions for symptomatic lung transplant-related anastomotic pulmonary
      artery stenosis (PAS). MATERIALS AND METHODS: From February 2008 to December
      2011, 354 lung transplants were performed. Pulmonary arteriography was performed
      in 19 patients (63% men; age, 57 y +/- 21, mean +/- SD; seven double-lung
      transplants) because of respiratory decompensation (mean 6.7 mo after
      transplant). Seven arteriograms were normal, and 12 showed significant PAS. One
      patient (5%) underwent angioplasty alone, and 11 patients (57%) underwent stent
      placement. RESULTS: All patients underwent general anesthesia, and femoral access
      was used for the intervention. Technical success was 100% in the 12 patients
      treated. Symptoms improved in all patients who underwent intervention, with
      resolution in 11 of 12 (92%). There were no major or minor complications. Three
      patients (16%) had recurrent symptoms after discharge secondary to chronic
      rejection or pneumonia. Two patients died as a result of sepsis and multiorgan
      failure at 2 days and 14 days, respectively, after undergoing only pulmonary
      arteriography. In-stent stenosis occurred in 1 (9%) patient who required
      additional stent placement. During a mean follow-up period of 11 months, the
      remaining stents were patent, and the patients were asymptomatic. CONCLUSIONS:
      Endovascular stent placement provides an alternative to open repair for
      transplant-related anastomotic PAS. It has low mortality and morbidity rates, and
      it has shown excellent short-term functional and anatomic outcomes.

PMID- 25851201
TI  - Unpacking the process of interpretation in evidence-based decision making.

PMID- 25851202
TI  - Factors Influencing Early Detection of Oral Cancer by Primary Health-Care
      Professionals.
AB  - The purposes of this study are to determine early detection practices performed
      by primary healthcare professionals, to compare medical and dental sub-groups,
      and to identify factors that influence the ability of medical and dental
      practitioners to recognize precancerous changes and clinical signs of oral
      cancer. A 28-item survey instrument was used to interview a total of 330
      Jordanian primary health-care professionals (165 dental and 165 medical). An oral
      cancer knowledge scale (0 to 31) was generated from correct responses on oral
      cancer general knowledge. An early detection practice scale (0 to 24) was
      generated from the reported usage and frequency of procedures in oral cancer
      examination. Also, a diagnostic ability scale (0 to 100) was generated from
      correct selections of suspicious oral lesions. Only 17.8 % of the participants
      reported that they routinely performed oral cancer screening in practices. Their
      oral cancer knowledge scores ranged from 3 to 31 with a mean of 15.6. The early
      detection practice scores ranged from 2 to 21 with a mean of 11.6. A significant
      positive correlation was found between knowledge scores and early detection
      practice scores (r = 0.22; p < 0.001). The diagnostic ability scores ranged from
      11.5 to 96 with a mean of 43.6. The diagnostic ability score was significantly
      correlated with knowledge scores (r = 0.39; p < 0.001), but not with early
      detection practice scores (r = 0.01; p = 0.92). Few significant differences were
      found between medical and dental primary care professionals. Continuous education
      courses on early diagnosis of oral cancer and oral mucosal lesions are needed for
      primary health-care professionals. 

PMID- 25851204
TI  - Selecting danger signals: dissociable roles of nucleus accumbens shell and core
      glutamate in predictive fear learning.
AB  - Conditioned stimuli (CSs) vary in their reliability as predictors of danger.
      Animals must therefore select among CSs those that are appropriate to enter into
      an association with the aversive unconditioned stimulus (US). The actions of
      prediction error instruct this stimulus selection so that when prediction error
      is large, attention to the CS is maintained and learning occurs but when
      prediction is small attention to the CS is withdrawn and learning is prevented.
      Here we studied the role of glutamate acting at rat nucleus accumbens shell
      (AcbSh) and core (AcbC) alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
      (AMPA) receptors in this selection of danger signals. Using associative blocking
      and unblocking designs in rats, we show that antagonizing AcbSh AMPA receptors
      via infusions of 2,3-dihydroxy-6-nitro-7-sulphamoyl-benzo[f]quinoxaline-2,3-dione
      (NBQX; 0.5 MUg) prevents the unblocking of fear learning, whereas antagonizing
      AcbC AMPA receptors via infusions of NBQX (0.5 MUg) prevents both the blocking
      and unblocking of fear learning. These results identify dissociable but
      complementary roles for AcbSh and AcbC glutamate acting at AMPA receptors in
      selecting danger signals: AcbSh AMPA receptors upregulate attention and learning
      to CSs that signal surprising USs, whereas AcbC AMPA receptors encode the
      predicted outcome of each trial.

PMID- 25851203
TI  - Factors Influencing Chemotherapy Goal Perception in Newly Diagnosed Cancer
      Patients.
AB  - Cancer patients who start receiving chemotherapy have difficulty in understanding
      the state of their disease, the prognosis, and the purpose of treatment. We used
      a survey to evaluate the extent of perception of chemotherapy goal among cancer
      patients. Two hundred sixteen cancer patients who received chemotherapy for the
      first time participated in the study. The presence of depression and anxiety was
      assessed using the "Hospital Anxiety and Depression Scale" (HAD). The consistency
      between the patients' perception of the chemotherapy goal and the physician's
      perception was described as "right," and the inconsistency was described as
      "wrong." Among the patients who participated in the survey, 53.2 % (n = 115) were
      receiving adjuvant treatment and 46.8 % (n = 101) were receiving palliative
      treatment for metastatic disease. The rate of right and wrong perception of the
      chemotherapy goal was 51.9 % (n = 108) and 32.2 % (n = 67), respectively, and the
      rate of confused patients was 18.9 % (n = 41). The level of education was shown
      to be the only parameter involved in accurate perception of the treatment purpose
      (hazard ratio (HR) = 0.444, p = 0.025, 95 % confidence interval (CI) 0.219
      0.903). In this study, there was a 51.9 % consistency between the physician's
      perception and that of the patient regarding the purpose of treatment. We
      demonstrated that the level of education was the unique factor in accurate
      perception of chemotherapy goal among cancer patients.

PMID- 25851206
TI  - Vascular pathology comes of age: Views and reviews in vascular medicine and
      biology.

PMID- 25851205
TI  - Skeletal muscle mass and quality: evolution of modern measurement concepts in the
      context of sarcopenia.
AB  - The first reports of accurate skeletal muscle mass measurement in human subjects
      appeared at about the same time as introduction of the sarcopenia concept in the
      late 1980s. Since then these methods, computed tomography and MRI, have been used
      to gain insights into older (i.e. anthropometry and urinary markers) and more
      recently developed and refined methods (ultrasound, bioimpedance analysis and
      dual-energy X-ray absorptiometry) of quantifying regional and total body skeletal
      muscle mass. The objective of this review is to describe the evolution of these
      methods and their continued development in the context of sarcopenia evaluation
      and treatment. Advances in these technologies are described with a focus on
      additional quantifiable measures that relate to muscle composition and 'quality'.
      The integration of these collective evaluations with strength and physical
      performance indices is highlighted with linkages to evaluation of sarcopenia and
      the spectrum of related disorders such as sarcopenic obesity, cachexia and
      frailty. Our findings show that currently available methods and those in
      development are capable of non-invasively extending measures from solely 'mass'
      to quality evaluations that promise to close the gaps now recognised between
      skeletal muscle mass and muscle function, morbidity and mortality. As the largest
      tissue compartment in most adults, skeletal muscle mass and aspects of muscle
      composition can now be evaluated by a wide array of technologies that provide
      important new research and clinical opportunities aligned with the growing
      interest in the spectrum of conditions associated with sarcopenia. 

PMID- 25851207
TI  - Quantitative analysis of inflammatory cells in aortic atherosclerosis of young
      adults.
AB  - Cellular analysis of aortic atherosclerotic lesions has been pursued extensively
      in recent years, although most of these investigations have involved the
      detection of inflammatory cells in chronically diseased tissue or artificially
      induced atherosclerosis in an animal model. Few studies have attempted to
      quantify accurately, using computer analysis systems, the degree of cellular
      infiltration in a statistically significant number of samples, in tissue from
      young adults. In this study, segments of human aortae were collected at autopsy
      from 29 individuals ranging in age from 15 to 35 years. The tissue was embedded
      in paraffin and stained using routine histological and automated
      immunohistochemical staining techniques. The sections were evaluated using
      advanced image analysis techniques to investigate the differences in cellular
      composition and cell activation between the dorsal and ventral aspects of the
      human aorta and to correlate these findings to the age of the subjects. These
      regions have been previously shown to have a high (dorsal) and low (ventral)
      probability of developing sudanophilic lesions. Our data demonstrated that
      statistically different cell populations exist in the dorsal and ventral regions
      of each vessel. The dorsal aspect (i.e., high-probability region) had a greater
      number of HAM56(+) (36.9% increase,p = 0.0002) and HLA-DRalpha(+) cells (44.2%
      increase,p = 0.0035) than did the ventral surface (i.e., low-probability region),
      although there were no significant differences in the number of CD43(+)
      lymphocytes. When grouped according to age, results showed significant increases
      in the dorsal region when considering HAM56(+) and HLA-DRalpha(+) cells (p = 0033
      and 0.046, respectively). Morphologically, a greater number of foam cell
      aggregates were found to occur in the dorsal region of the vessel than in the
      ventral portion. Our results indicate that the microarchitecture and cellular
      composition of the dorsal and ventral aorta are significantly different, with
      these variations becoming more marked with age. 

PMID- 25851208
TI  - Covert congenital cardiovascular malformations discovered in an autopsy series of
      nearly 5,000 cases.
AB  - The objective of this study was to assess the prevalence of covert congenital
      cardiac malformations. A retrospective analysis was made of a personal series of
      4,953 consecutive postmortem examinations performed over 35 years (1946-1980) in
      a mixed urban and rural region of North Lincolnshire, England. The subjects were
      4,210 adults and 743 children (under the age of 16 years). There were 1,635
      hospital cases and 3,318 coroner's cases; of the latter, 2,651 were instances of
      sudden and unexpected death. Four adults and 99 children with known or suspected
      congenital heart disease were excluded from the analysis. Of the remaining 4,850
      cases, 25 had benign covert cardiovascular malformation (0.52%), and in
      approximately 54 more a covert malformation was considered to have been a
      possible contributor to death. This latter group consisted of 44 cases of
      bifoliate calcified aortic valves, 6 cases of cardiomyopathy, and 4 miscellaneous
      cases. As sudden deaths were grossly over-represented in the series, an
      approximate correction factor reduced the prevalence of this group to 0.16%,
      giving a prevalence of 0.68% for all covert cases. According to these data, the
      true prevalence of congenital cardiac malformations is probably about twice that
      of the generally accepted level in live births. The implications for
      epidemiological studies pertinent to the etiology of congenital heart disease are
      indicated. 

PMID- 25851209
TI  - Nonpredictive value of fibrosis in dilated cardiomyopathy treated with
      metoprolol.
AB  - Therapy with beta-adrenergic blocking agents has been advocated as a potential
      useful approach in heart failure. Recent studies suggest that histologic
      parameters may be helpful in assessing the effectiveness of beta-blocker
      treatment in dilated cardiomyopathy (DCM). In order to predict the response to
      beta-blockers in DCM, fibrous tissue was evaluated at endomyocardial biopsy (EMB)
      in 45 patients (pts) with a mean left ventricular ejection fraction of 0.28 +/-
      0.07, who were successively long-term treated with metoprolol (M) (mean dosage
      138 +/-26 mg/die). EMB was performed from left (n = 32) or right (n = 13)
      ventricle by means of a King's bioptome or the Cordis adaptation of this
      instrument. Quantification of fibrous tissue was performed at 9 * magnification
      and with a computerized morphometric system. Qualitative evaluation at light
      microscopy distinguished four types of fibrosis: pericellular, perivascular,
      focal, and endocardial. Volume fraction of fibrous tissue ranged from 1.3 to
      35.5% (mean 12.1 +/- 9.3%) and was not significantly correlated with any clinical
      variable considered. After 24 +/- 12 months of treatment, 25 pts were considered
      improved (group A), whereas the remaining 20 pts were considered not improved
      (group B), according to criteria based on ejection fraction, left ventricular end
      diastolic diameter, filling pattern at Doppler-Echocardiography, cardiothoracic
      ratio, NYHA functional class, and exercise duration at ergometric test. Volume
      fraction of fibrous tissue did not differ significantly between the two groups
      (group A = 12.1 +/- 9.1%; group B = 11.3 +/- 9.6%;p = NS). Dominant pericellular
      type of fibrosis was equally distributed between the two groups (group A = 9 25
      pts, 36%; group B = 10 20 pts, 50%), whereas a perivascular and/or focal
      replacement fibrosis was more frequent in group A (group A = 10 20 pts, 50%;
      group B = 2 20 pts, 10%; p = .05, OR 5.55 at univariate analysis). At
      multivariate analysis mean aortic blood pressure was the only variable
      discriminating the two groups; the type of fibrosis, although not statistically
      significant, maintained a high value of odds-ratio (5.23). In conclusion, extent
      of total fibrosis assessed by EMB may range widely in patients with DCM, is not
      correlated with the most important clinical variables, and is not predictive of
      long-term response to beta-blocker treatment. Otherwise, prevalent perivascular
      and/or focal replacement fibrosis could be associated with a higher probability
      of improvement after long-term beta-blocker treatment. 

PMID- 25851210
TI  - Myocardial vacuolization, a marker of ischemic injury, in surveillance cardiac
      biopsies posttransplant: Correlations with morphologic vascular disease and
      endothelial dysfunction.
AB  - Allograft vasculopathy (AV) causes intimal thickening with progressive luminal
      obstruction, endothelial dysfunction, and abnormal vasomotion. Subendocardial
      vacuolization indicating ongoing ischemia was observed at autopsy in transplanted
      hearts with severe AV. Whether myocyte vacuolization can be observed with lesser
      degrees of AV in cardia transplant patients has not been reported. Thirty-nine
      cardiac transplant patients without flow-limiting disease in large epicardial
      arteries underwent invasive assessment of AV. Eight to 10 segments of the left
      anterior descending artery were analyzed by intracoronary ultrasound, and an
      average intimal index was calculated. Endothelial response to acetylcholine was
      assessed with serial quantitative angiography. Endomyocardial biopsies taken 5 to
      7 days prior to the invasive studies were histopathologically reviewed for the
      presence of small intramyocardial arteries and myocyte vacuolization. Myocyte
      vacuolization was evident in biopsies from 20 patients (51%). Intramyocardial
      arteries were observed in 30 cases (76%); 14 had abnormal arteries. All patients
      had some degree of intimal thickening by intracoronary ultrasound, and 7 (17 %)
      had severely abnormal average intimal index (>0.2). Endothelial dysfunction was
      present in 23 patients (58%). Vacuolization failed to show an association with
      abnormal small artery histology or large epicardial artery ultrasound disease.
      However, a significant association between vacuolization and endothelial
      dysfunction was observed (p = 0.05). Myocyte vacuolization, possibly indicating
      ischemic injury, is common in biopsies from cardiac transplant patients and is
      associated with abnormal acetylcholine response in large epicardial arteries. We
      speculate that myocyte vacuolization may be caused at least in part by impaired
      coronary flow associated with endothelial dysfunction. 

PMID- 25851211
TI  - Cardiomyopathy in rats with Walker 256 tumor: The potential role of microvascular
      disease in its genesis.
AB  - Considering that diffuse abnormalities of myocardial microcirculation with
      transient ischemia have been suggested to play a role in the genesis of
      myocytolytic necrosis, characteristic lesion of dilated or congestive
      cardiomyopathies, and the bloodstream is the most common pathway for
      dissemination of cancer cells, which gain access to the microcirculation, the
      present study was undertaken to search for morphologic and electrocardiographic
      evidence of myocardial damage associated with microcirculatory disease in rats
      experimentally inoculated with the Walker 256 tumor. Young albino rats inoculated
      intramuscularly with the Walker 256 tumor developed a cardiomyopathy
      characterized by diffuse small foci of myocytolytic necrosis, decreased thickness
      of the mean left midventricular wall associated with reduced size of the minor
      diameter of myocytes, and electrocardiographic abnormalities reflecting the
      myocardial damage, correlated with the presence of a microvascular disease,
      characterized by intramyocardial microvessels (less than 50 MUm in diameter)
      partially or totally occluded because of entrapment of tumor cells and fibrin
      platelet/tumor cell-cellular debris thrombi. The occlusive or subocclusive small
      vessel lesions preceded the development of the myocytolytic necrosis, suggesting
      that the microvascular disease would play an important role in the process of
      focal micronecrosis and consequent electrocardiographic changes. However, it must
      be taken into account that the tumor thromboemboli can generate related factors
      that could promote cell injury and cell death. In conclusion, the hematogenic
      dissemination of Walker 256 cells promotes the development of an experimental
      cardiomyopathy attributable, at least in part, to microvascular obliterative
      changes in the myocardium. 

PMID- 25851212
TI  - Persistence of spongy myocardium with embryonic blood supply in an adult.
AB  - Gross presence of the embryonic pattern of myoarchitecture and of a sinusoid
      blood supply was found in the apical part of the left ventricle in a man who had
      been diagnosed with nonobstructive hypertrophic cardiomyopathy during life and
      who died suddenly at age 21 years. This is a first description of this finding in
      an adult with an otherwise normal heart and coronary arteries. The features of
      the cardiac lesions provide support for the current embryological views on
      ontogenesis of human myocardial structure and blood supply. 

PMID- 25851213
TI  - Value of the endomyocardial biopsy in the diagnosis of toxoplasmosis after heart
      transplantation.

PMID- 25851215
TI  - Comment on 'Comparative survival of commercial probiotic formulations: tests in
      biorelevant gastric fluids and real-time measurements using microcalorimetry'.

PMID- 25851214
TI  - Hsp90 regulates the dynamics of its cochaperone Sti1 and the transfer of Hsp70
      between modules.
AB  - The cochaperone Sti1/Hop physically links Hsp70 and Hsp90. The protein exhibits
      one binding site for Hsp90 (TPR2A) and two binding sites for Hsp70 (TPR1 and
      TPR2B). How these sites are used remained enigmatic. Here we show that Sti1 is a
      dynamic, elongated protein that consists of a flexible N-terminal module, a long
      linker and a rigid C-terminal module. Binding of Hsp90 and Hsp70 regulates the
      Sti1 conformation with Hsp90 binding determining with which site Hsp70 interacts.
      Without Hsp90, Sti1 is more compact and TPR2B is the high-affinity interaction
      site for Hsp70. In the presence of Hsp90, Hsp70 shifts its preference. The linker
      connecting the two modules is crucial for the interaction with Hsp70 and for
      client activation in vivo. Our results suggest that the interaction of Hsp70 with
      Sti1 is tightly regulated by Hsp90 to assure transfer of Hsp70 between the
      modules, as a prerequisite for the efficient client handover. 

PMID- 25851216
TI  - Management of chronic spontaneous urticaria in the elderly.
AB  - The guidelines for the management of urticaria in adults and children have been
      revised and updated recently. However, there are few data in the literature
      concerning several aspects of this disease in the elderly (e.g., epidemiology,
      etiopathogenesis, clinical aspects, association with co-morbidities, efficacy and
      safety profiles of treatments, and management strategies). This is an obvious
      deficiency in the data, as this disease causes a deterioration in quality of
      life, affecting the quality of sleep, everyday life habits and activities, and
      inducing severe disability. Chronic spontaneous urticaria (CSU) can also be
      associated with internal, infectious, autoimmune, or neoplastic diseases. It is
      therefore necessary to pay particular attention to these clinical issues through
      appropriate clinical examinations. At the same time, the specific features of
      medications used to treat CSU in the elderly should be carefully evaluated, as
      its pharmacological treatment raises a number of problems related both to the
      clinical condition of the patient and to concomitant diseases, as well as to the
      polypharmacotherapy, which is common in older subjects and may cause safety
      problems because of the drug interactions. Non-sedating new-generation
      antihistamines are the mainstay treatment of CSU for the elderly. The efficacy
      and safety of alternative treatment options have not been assessed in the
      geriatric population with CSU; corticosteroids and cyclosporine (ciclosporin)
      should be used by this population with extreme caution. Similarly, there are no
      data regarding the actual safety profile of the new-generation antihistamines at
      higher doses than those recommended in elderly patients. 

PMID- 25851218
TI  - Mercury levels in common (Actitis hypoleucos) and green (Tringa ochropus)
      sandpipers from west-central Iran.
AB  - Mercury concentrations were examined in the liver, kidneys, and tail and breast
      feathers of common and green sandpipers from Zayanderud Dam in west-central Iran.
      The aim was to provide indirect information about habitat contamination. Tail
      feathers of both species had higher mercury levels compared to other tissues.
      Moreover, tissues of common sandpipers had significantly higher mercury
      concentrations compared to tissues of green sandpipers. Male specimens of both
      species had higher values of mercury compared to females. The pattern of larger
      body size-higher mercury body burden was not completely true in the current
      study. Smaller and shorter common sandpipers had higher mercury concentrations
      compared to taller and heavier green sandpipers. At the intraspecific level, body
      weight was positively correlated with mercury concentrations in tissues of common
      sandpipers. Based on the data presented here, it appears that these sandpipers,
      especially common sandpipers, are at potential risk from the toxic effects of
      mercury. 

PMID- 25851219
TI  - Cardiac fibroblasts form and function.
AB  - The formation and structure of the extracellular matrix (ECM) that makes up the
      cardiac interstitum is well known yet the underlying mechanisms that regulate the
      interstitum are poorly known. This review focuses on the role of the cardiac
      fibroblast in the formation and regulation of the ECM components during cardiac
      development and in response to physiological and pathological stimulation. The
      role of ECM receptors (integrins), cellular phenotype, and chemical and
      mechanical signaling by cardiac fibroblasts are discussed. 

PMID- 25851217
TI  - Respiratory syncytial virus infection in older adults: an under-recognized
      problem.
AB  - Human respiratory syncytial virus (RSV) is an enveloped, single-stranded,
      negative-sense RNA virus and member of the Paramyxoviridae family of the genus
      Pneumovirus that was first reported as a major pathogen in pediatric populations.
      However, since its discovery, RSV has not infrequently been detected in adults.
      Reinfection occurs throughout life, with more severe disease occurring in older
      adults, immunocompromised patients, and those with underlying cardiopulmonary
      disease. Initially described as the cause of nursing home outbreaks of
      respiratory disease, there is a now significant body of literature describing the
      clinical importance of RSV in older adults in a multitude of settings including
      long-term care, adult daycares, and in community-dwelling adults. Moreover,
      recent reports from China and other countries emphasize that RSV is a global
      pathogen that will become increasingly important in developed nations with aging
      populations. Annual attack rates in the USA range from 2 to 10% in community
      dwelling older adults and 5-10% in older adults living in congregate settings.
      Population-based calculations of the proportion of acute respiratory illnesses
      attributable to RSV estimate that 11,000 elderly persons die annually in the USA
      of illnesses related to RSV infection. Clinical manifestations of RSV infections
      are similar to that of other viral respiratory pathogens and include cough, nasal
      congestion, rhinorrhea, sore throat, and dyspnea. Lower respiratory tract disease
      is common and may result in respiratory failure (8-13%) or death (2-5%). Recent
      advances in molecular diagnostics have made it possible to rapidly identify RSV
      infection using nucleic acid amplification tests, although clinicians will need
      to suspect the diagnosis when viral activity is high. At the present time,
      treatment is supportive. Effective antiviral agents for the treatment and
      vaccines for prevention of RSV remain a significant unmet medical need in the
      older adult population.

PMID- 25851220
TI  - Cardiac integrins the ties that bind.
AB  - An elaborate series of morphogenetic events must be precisely coordinated during
      development to promote the formation of the elaborate three-dimensional structure
      of the normal heart. In this study we focus on discussing how interconnections
      between the cardiac myocyte and its surrounding environment regulate cardiac form
      and function. In vitro experiments from our laboratories provide direct evidence
      that cardiac cell shape is regulated by a dynamic interaction between
      constituents of the extracellular matrix (ECM) and by specific members of the
      integrin family of matrix receptors. Our data indicates that phenotypic
      information is stored in the tertiary structure and chemical identity of the ECM.
      This information appears to be actively communicated and transduced by the
      alpha1beta1 integrin molecule into an intracellular signal that regulates cardiac
      cell shape and myofibrillar organization. In this study we have assessed the
      phenotypic consequences of suppressing the expression and accumulation of the
      alpha1 integrin molecule in aligned cultures of cardiac myocytes. In related
      experiments we have examined how the overexpression of alpha2 and alpha5
      integrin, integrins normally not present or present at very low copy number on
      the cell surface of neonatal cardiac myocytes, affect cardiac protein metabolism.
      We also consider how biochemical signals and the mechanical signals mediated by
      the integrins may converge on common intracellular signaling pathways in the
      heart. Experiments with the whole embryo culture system indicate that angiotensin
      II, a peptide that carries information concerning cardiac load, plays a role in
      controling cardiac looping and the proliferation of myofibrils during
      development. 

PMID- 25851221
TI  - Regulation of myocardial extracellular matrix components by mechanical and
      chemical growth factors.
AB  - The cardiac fibroblast is numerically the most abundant cell in the myocardium
      and is responsible for the deposition of the extracellular matrix (ECM). The
      cardiac ECM is a hierarchical, three-dimensional network in the heart, of which
      fibrillar collagens types I and III are the major structural components. Normal
      and pathological deposition of fibrillar collagen in the heart appears to rely on
      the regulation of ECM components such as fibronectin. Many humoral mediators have
      been noted to modulate the function of cardiac fibroblasts. In particular,
      angiotensin II and transforming growth factor-beta1 have gained recent attention.
      However, growth factors such as endothelin, ANF, and catecholamines among others
      are also noted to modify cardiac fibroblast function. Cardiac fibroblasts are
      also capable of synthesizing and releasing many of the above mentioned growth
      factors which in an autocrine or paracrine fashion may modulate myocardial cell
      functions. Cardiac fibroblasts have also been noted to secrete a potent growth
      factor that stimulates cardiac myocyte hypertrophy. Recent studies using stretch
      apparatuses on cardiac fibroblasts also indicate that these cells respond to such
      types of mechanical stimuli. Unfortunately, little is known about human cardiac
      fibroblasts since most studies have utilized cells isolated from animal species.
      The following study summarizes our current state of knowledge in the field of
      mechanical and chemical regulation of myocardial ECM. 

PMID- 25851222
TI  - Dynamic role of extracellular matrix metalloproteinases in heart failure.
AB  - In chronic congestive heart failure, an illness affecting more than 4 million
      Americans, there is extensive myocardial extracellular matrix (ECM) remodeling.
      Failing human ventricular myocardium contains activated matrix metalloproteinases
      (MMPs) which are involved in adverse ECM remodeling. Our studies support the
      concept that impaired ECM remodeling and MMP activation are, in part, responsible
      for the cardiac structural deformation during heart failure. There is no known
      program which has declared its aim the investigation of regulation of fibrosis in
      hypertrophy and disruption of ECM in cardiac dilatation and failure. The
      development of transgenic technology, and emerging techniques for in vivo gene
      transfer, suggest a strategy for improving cardiac function by overexpressing or
      down regulation of the ECM components such as MMPs, tissue inhibitor of
      metalloproteinases (TIMPs), transforming growth factor beta1 (TGFbeta), decorin,
      collagen, and integrins in heart failure. 

PMID- 25851223
TI  - Myocardial extracellular matrix remodeling with the development of pacing induced
      congestive heart failure contributory mechanisms.
AB  - The myocardial fibrillar collagens ensure structural integrity of adjoining
      myocytes, provide the means by which myocyte shortening is translated into
      overall left ventricular (LV) pump function, and have been postulated to be
      essential for maintaining alignment of myofibrils within the myocyte through a
      collagen-integrin-cytoskeletal-myofibril relation. This laboratory has performed
      a series of studies in order to examine the relationship between changes in
      myocardial collagen matrix components to LV function and geometry which occurred
      in a model of congestive heart failure (CHF) induced by chronic rapid pacing. In
      this model of CHF, indices of LV pump function are reduced and accompanied by
      significant dilation. LV fibrillar collagen concentration was reduced and salt
      extractable collagen, which reflects collagen cross-linking, was increased with
      the development of CHF. LV myocyte adhesion capacity to basement membrane
      substrates was reduced with pacing CHF. Results from a recently completed series
      of studies have demonstrated alterations in the expression and activity of the
      collagenases, or matrix metalloproteinases (MMPs) occur during the progression of
      CHF. Increased LV myocardial MMP abundance and activity occurred with pacing CHF
      and were associated with the development of LV dilation, wall thinning, and pump
      dysfunction. These results suggest that changes within the myocardial
      extracellular space are a dynamic process and accompany the LV remodeling and
      dysfunction which occurs with the development of a CHF process. Future studies
      which define the contributory role of MMP synthesis and activation in the LV
      remodeling process which occurs in the setting of CHF will likely identify unique
      therapeutic modalities to slow the progression of this disease process. 

PMID- 25851224
TI  - An unusual coronary vein lesion thrombus with calcification.
AB  - In this article, a patient with chronic renal failure and probable secondary
      hyperparathyroidism is described; calcification of a variety of cardiac and other
      structures complicated the latter. Calcification of an occlusive thrombus in the
      great cardiac vein and coronary sinus was identified by echocardiography,
      although not initially appreciated as such. The echocardiographic similarity of
      this lesion to mitral annular calcification is discussed. 

PMID- 25851225
TI  - Thyroid heterotopia as a rare cause of intrapericardial tumoral mass case report
      and review of the literature.
AB  - This article describes the interesting discovery of a large tumoral mass formed
      of heterotopic thyroid tissue inside the pericardial cavity of an elderly man who
      died of unrelated causes. Heterotopic thyroid tissue may be found in many
      locations throughout the body. Intracardiac and intrapericardial locations,
      however, are exceptionally rare-this is only the second report of
      intrapericardial thyroid heterotopia. Such cases may be explained by the
      proximity of the developing cardiac structures and the foregut, the latter
      containing thyroid primordia during early embryogenesis. 

PMID- 25851226
TI  - Large epicardial lipoma associated with rupture of the interventricular septum
      after an acute myocardial infarct.
AB  - We report a case of a large epicardial lipoma associated with an unusual rupture
      of an infarcted interventricular septum. The proximity of the attachment of the
      lipoma to the rupture site, together with the unusual shape and location of the
      rupture, suggest that the lipoma perpetrated the rupture. 

PMID- 25851227
TI  - Using quality indicators to compare outcomes of permanent cardiac pacemaker
      implantation among publicly and privately funded patients.
AB  - BACKGROUND: Funding source/insurance status has been associated with disparity in
      the management and outcomes of cardiovascular disease, with poorer outcomes among
      disadvantaged groups. AIM: Using proposed quality indicators for permanent
      pacemaker (PPM) implantation and administrative data, this study aimed to
      determine whether quality indicator-based outcomes of PPM implantation were
      comparable for publicly and privately funded patients within Australia's two-tier
      health system. METHODS: A population-based cohort study of adults implanted with
      a PPM between 1995 and 2009 in Western Australia. The association of funding
      outcomes derived from linked administrative data was tested in multivariate
      logistic regression models. RESULTS: There were 9748 PPMs implanted, 48% being
      among privately funded patients. The mean age was 75 years for both public and
      private patients. Private patients had better health status (fewer with cardiac
      conditions and lower non-cardiac comorbidity scores), were less likely to be an
      emergency admission (33% vs 60%, P < 0.001) and more likely to have dual- or
      triple-chamber pacing. Mean length of stay was significantly greater for private
      patients (4.3 (standard deviation 6.3) vs 5.1 (6.8) days <0.001), related to
      longer elective admissions. Crude mortality was lower for private patients in
      hospital (0.7 vs 1.3%), 30-day post-procedure (1.3 vs 2.1%) and at 1 year (7.3 vs
      9.5%). Emergency admission, comorbidity and other demographic and clinical
      factors, not funding source, were significant predictors of these outcomes.
      CONCLUSIONS: There was no difference between publicly and privately funded
      patients in study outcomes, after adjustment for demographic and clinical
      factors. The exception was longer hospital stay for elective PPM among privately
      funded patients.

PMID- 25851228
TI  - A new insight into ductile fracture of ultrafine-grained Al-Mg alloys.
AB  - It is well known that when coarse-grained metals undergo severe plastic
      deformation to be transformed into nano-grained metals, their ductility is
      reduced. However, there are no ductile fracture criteria developed based on grain
      refinement. In this paper, we propose a new relationship between ductile fracture
      and grain refinement during deformation, considering factors besides void
      nucleation and growth. Ultrafine-grained Al-Mg alloy sheets were fabricated using
      different rolling techniques at room and cryogenic temperatures. It is proposed
      for the first time that features of the microstructure near the fracture surface
      can be used to explain the ductile fracture post necking directly. We found that
      as grains are refined to a nano size which approaches the theoretical minimum
      achievable value, the material becomes brittle at the shear band zone. This may
      explain the tendency for ductile fracture in metals under plastic deformation. 

PMID- 25851229
TI  - Properties of the Urothelium that Establish the Blood-Urine Barrier and Their
      Implications for Drug Delivery.
AB  - The primary function of the urinary bladder is to store and periodically release
      urine. How the urothelium prevents permeation of water, ions, solutes, and
      noxious agents back into the bloodstream and underlying tissues as well as
      serving as a sensor and transducer of physiological and nociceptive stimuli is
      still not completely understood, and thus its unique functional complexity
      remains to be fully elucidated. This article reviews the permeation routes across
      urothelium as demonstrated in extensive morphological and electrophysiological
      studies on in vivo and in vitro urothelia. We consider the molecular and
      morphological structures of urothelium and how they contribute to the
      impermeability of the blood-urine barrier. Based on the available data, the
      extremely low permeability properties of urothelium can be postulated. This
      remarkable impermeability is necessary for the normal functioning of all mammals,
      but at the same time represents limitations regarding the uptake of drugs.
      Therefore, the current progress to overcome this most resilient barrier in our
      body for drug therapy purposes is also summarized in this review. 

PMID- 25851230
TI  - Towards Understanding the Role of the Na2+-Ca2+ Exchanger Isoform 3.
AB  - The Na2+-Ca2+ exchanger (NCX) is critical for Ca2+ homeostasis throughout the
      body. Of the three isoforms in the NCX family, NCX1 has been extensively studied,
      providing a good basis for understanding the molecular aspects of the NCX family,
      including structural resemblances, stoichiometry, and mechanism of exchange.
      However, the tissue expression of the third isoform of the family, NCX3, together
      with its proposed involvement in the Ca2+ fluxes of the endoplasmic reticulum and
      the mitochondria suggests a distinctive role for this isoform. Investigations of
      the exchanger revealed the involvement of NCX3 in diverse processes such as bone
      formation, TNF-alpha production, slow-twitch muscle contraction, and long-term
      potentiation in the hippocampus. Furthermore, the study of its posttranslational
      modification, its cleavage by the Ca2+-sensitive protease, calpain, and its
      upregulation in numerous stress conditions linked NCX3 to the aberrant Ca2+
      influx seen during neuronal excitotoxicity in Alzheimer's disease, brain stroke,
      and neuronal injuries. Hence, beyond its role in calcium homeostasis, NCX3 plays
      an important role in stress conditions, neuronal excitotoxicity, and metabolism
      and is thereby a key element in many cell types. The present review aims to
      survey the knowledge on NCX3, focusing on the recent discoveries on its
      functional and structural properties, and discusses the implications of NCX3 in
      both physiological and pathological conditions.

PMID- 25851231
TI  - Hybrid repair of rare type IIIb endoleaks from an abdominal endograft: repeatedly
      undetected endoleaks.
AB  - We report a rare case of massive type IIIb endoleaks from an abdominal endograft,
      which were difficult to diagnose and required hybrid repair (including open
      surgery). The patient had previously undergone three catheter interventions for
      type Ia and II endoleaks after abdominal endografting. However, the abdominal
      aortic aneurysm gradually enlarged and required hybrid treatment (including an
      open repair), to successfully perform aneurysmorrhaphy and additional endograft
      insertions for the massive type IIIb endoleaks. 

PMID- 25851232
TI  - High perceived sensitivity to medicines is associated with higher medical care
      utilisation, increased symptom reporting and greater information-seeking about
      medication.
AB  - PURPOSE: The belief that one is especially sensitive to the actions and side
      effects of medicines can influence treatment adherence and side-effect reporting.
      In this study, we investigated the prevalence of perceived medication sensitivity
      in the general population and its relationship to symptom complaints, information
      seeking about medications, use of medical care and demographic factors. METHODS:
      A nationally representative sample of 1000 New Zealand residents completed the
      Perceived Sensitivity to Medicines scale and symptoms experienced during the
      previous 7 days. Demographic data and medical visits, medication use and
      information seeking about medicines were also collected. RESULTS: Over 20% of the
      general population reported being very sensitive to the effects of medication
      (20.2%) and that small amounts of medicines can upset their body (25.3%).
      Participants who reported high levels of perceived sensitivity to medicines
      reported significantly more symptoms (M = 9.54, SE = 0.47) than people with low
      (M = 5.04, SE = 0.49) or moderate (M = 5.91, SE = 0.24) levels, ps < .001. This
      relationship was strongest in participants who were currently taking prescription
      medication. Those with high perceived sensitivity also reported being more likely
      to seek information about medicines, and had significantly more general
      practitioner visits. CONCLUSIONS: Perceived sensitivity to medicines is common in
      the population and associated with important clinical variables including
      information seeking, GP visits and symptom reporting. Identifying patients with
      higher perceived sensitivity to medicines may improve patient care by providing
      the basis for targeted and personalised interventions to reduce side effects and
      improve adherence to medications.

PMID- 25851233
TI  - Prodromal symptoms associated with acute coronary syndrome acute symptom
      presentation.
AB  - OBJECTIVE: Prodromal symptoms (PS), indicative of myocardial ischemia, are
      frequently unrecognized by individuals prior to an acute coronary syndrome (ACS).
      ACSs are the leading cause of death worldwide. This study describes (1) the
      prevalence and association of PS with patients' baseline ACS-related acute
      symptoms of pain intensity and state anxiety and (2) the relationship of PS to co
      morbidity. METHODS: An exploratory sub-analysis was performed. Cross sectional
      data identified prodromal predictors of ACS pain intensity (numeric rating scale
      0-10 (NRS)) and state anxiety (Speilberger state-trait anxiety personality
      inventory (STAI)). ACS patients (n=121) admitted to a community rural emergency
      department completed the prodromal symptom screening scale (PS-SS) and reported
      baseline cardiac pain intensity, state, and trait anxiety. RESULTS: Increased ACS
      pain intensity was associated with PS. Median pain scores were higher by two
      points for those with prodromal headache, p=0.006, and anxiety, p=0.017, and one
      point higher for those with sleep disturbances, p=0.012. PS were not associated
      with state or trait anxiety. Hypertensive individuals were 7.5 times more likely
      to experience prodromal fatigue prior to their ACS event. CONCLUSION: Results
      extend current knowledge of the predictive value that prodromal headache, sleep
      disturbance and anxiety may have on individuals' acute symptom presentation. A
      prospective, prognostic study is required in order to determine whether PS are
      predictive of adverse cardiac events and if PS are a stronger predictor of ACS
      acute symptom presentation, compared with typical ACS-related co-morbidities.

PMID- 25851234
TI  - Complement system modulation as a target for treatment of arrhythmogenic
      cardiomyopathy.
AB  - Inflammation may contribute to disease progression in arrhythmogenic
      cardiomyopathy (ACM). However, its role in this process is unresolved. Our goal
      was to delineate the pathogenic role of the complement system in a new animal
      model of ACM and in human disease. Using cardiac histology, echocardiography, and
      electrocardiography, we have demonstrated that the desmin-null mouse (Des-/-)
      recapitulates most of the pathognomonic features of human ACM. Massive complement
      activation was observed in the Des-/- myocardium in areas of necrotic cells
      debris and inflammatory infiltrate. Analysis of C5aR-/-Des-/- double-null animals
      and a pharmaceutical approach using a C5a inhibitor were used to delineate the
      pathogenic role of the complement system in the disease progression. Our findings
      indicate that inhibiting C5aR (CD88) signaling improves cardiac function,
      histopathology, arrhythmias, and survival after endurance. Containment of the
      inflammatory reaction at the initiation of cardiac tissue injury (2-3 weeks of
      age), with consequently reduced myocardial remodeling and the absence of a direct
      long-lasting detrimental effect of C5a-C5aR signaling on cardiomyocytes, could
      explain the beneficial action of C5aR ablation in Des-/- cardiomyopathy. We
      extend the relevance of these findings to human pathophysiology by showing for
      the first time significant complement activation in the cardiac tissues of
      patients with ACM, thus suggesting that complement modulation could be a new
      therapeutic target for ACM.

PMID- 25851235
TI  - Transcriptional networks implicated in human nonalcoholic fatty liver disease.
AB  - The transcriptome of nonalcoholic fatty liver disease (NAFLD) was investigated in
      several studies. However, the implications of transcriptional networks in
      progressive NAFLD are not clear and mechanisms inducing transition from
      nonalcoholic simple fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH) are
      still elusive. The aims of this study were to (1) construct networks for
      progressive NAFLD, (2) identify hub genes and functional modules in these
      networks and (3) infer potential linkages among hub genes, transcription factors
      and microRNAs (miRNA) for NAFLD progression. A systems biology approach by
      combining differential expression analysis and weighted gene co-expression
      network analysis (WGCNA) was utilized to dissect transcriptional profiles in 19
      normal, 10 NAFL and 16 NASH patients. Based on this framework, 3 modules related
      to chromosome organization, proteasomal ubiquitin-dependent protein degradation
      and immune response were identified in NASH network. Furthermore, 9 modules of co
      expressed genes associated with NAFL/NASH transition were found. Further
      characterization of these modules defined 13 highly connected hub genes in NAFLD
      progression network. Interestingly, 11 significantly changed miRNAs were
      predicted to target 10 of the 13 hub genes. Characterization of modules and hub
      genes that may be regulated by miRNAs could facilitate the identification of
      candidate genes and pathways responsible for NAFL/NASH transition and lead to a
      better understanding of NAFLD pathogenesis. The identified modules and hub genes
      may point to potential targets for therapeutic interventions. 

PMID- 25851236
TI  - Genome-wide analysis of the family 1 glycosyltransferases in cotton.
AB  - Family 1 GT, designated as UGT, is the largest and most functionally important
      multigene family in the plant kingdom. In this study, we carried out a genome
      wide identification, analysis, and comparison of 142, 146, and 196 putative UGTs
      from Gossypium raimondii, Gossypium arboreum, and Gossypium hirsutum,
      respectively. All members present the 44 amino-acid conserved consensus sequence
      termed the plant secondary product glycosyltransferase motif. According to the
      phylogenetic relationship among the cotton UGT proteins and those from other
      species, GrUGTs and GaUGTs could be classified into 16 major phylogenetic groups
      (A-P), whereas GhUGTs are classified into 15 major phylogenetic groups with a
      lack of group C. All cotton UGTs are dispersed throughout the chromosomes and are
      displayed in clusters with the same open reading frame orientation. The expansion
      of them appears to result from genome duplication and rearrangement. Two
      conserved introns, A and B, are detected in most of the intron-containing-UGTs in
      G. raimondii and G. arboreum, whereas only intron A is detected in the intron
      containing-UGTs in G. hirsutum. Furthermore, expression patterns of the UGT genes
      in G. hirsutum wild type and its near isogenic fuzzless-lintless mutant at the
      stage of fiber initiation were analyzed using the RNA-seq data. Overall, this
      study not only deepens our understanding of the structure, phylogeny, evolution,
      and expression of cotton UGT genes, but also provides a solid foundation for
      further cloning and functional studies of the UGT family genes. 

PMID- 25851237
TI  - Identification and characterization of paternal-preferentially expressed gene NF
      YC8 in maize endosperm.
AB  - Gene imprinting describes an epigenetic phenomenon, whereby genetically identical
      alleles are differentially expressed dependent on parent-of-origin. Some
      imprinted genes belonged to NUCLEAR FACTOR Y (NF-Y) transcription factors, which
      were involved in many important metabolic processes in plant. The
      characterizations of imprinted genes are of great importance for their function
      exploration. In this paper, 15 non-redundant NF-YC genes were identified in the
      maize genome and the paternally expressed gene NF-YC8 was further analyzed. NF
      YC8 primarily expressed in maize immature ear and tassel and phylogenetic
      analysis showed that NF-YC8 was highly homologous with Arabidopsis thaliana NF
      YC2 genes which function in regulation of the flowering processes, ER stress
      response. Furthermore, NF-YC8 was a differential, gene-specific imprinted gene at
      14 DAP and persistently imprinted throughout later endosperm development in the
      B73/Mo17 genetic background. Bisulfite sequencing for NF-YC8 in maize endosperm
      showed that the paternal alleles were higher methylated (CG, CHG and CHH
      contexts) than maternal alleles in the 5' upstream region, and the coding region
      was highly methylated in CG context. Additionally, TE (CG, CHG and CHH contexts)
      and repetitive region (CG and CHG contexts) were all highly methylated. These
      results are the first description of evolution and molecular characterization of
      maize NF-YC8 and will provide new references for maize NF-YC genetic analysis. 

PMID- 25851238
TI  - Post-Disaster Mental Health Among Parent-Child Dyads After a Major Earthquake in
      Indonesia.
AB  - The interdependent adjustment of children and their parents following disasters
      has been well documented. We used the Actor-Partner Interdependence Model (APIM)
      to provide an appropriate analytical framework for examining how family members
      may contribute to each other's post-disaster mental health. Independent self
      reports were collected from parent-child dyads (n = 397) residing in a rural
      community in Indonesia that was devastated by a major earthquake. Elementary
      school children (M = 10 years; 51 % female) and one of their parents (M = 41
      years; 73 % female) each reported on their disaster exposure, posttraumatic
      stress (PTS) symptoms, and general distress. The APIM was used to examine mental
      health within dyads and moderation by gender across dyads. Children reported
      lower disaster exposure and fewer PTS symptoms, but similar general distress
      levels, as their parents. Children's and parents' disaster-specific PTS symptoms
      were the strongest predictor of their own general distress. Parents' PTS symptoms
      were associated with children's general distress (b = 0.14, p < 0.001), but
      children's PTS symptoms were not associated with parents' general distress (b = 
      0.02, p > 0.05). Findings were not moderated by parents' or children's gender.
      Although children and parents may respond differently to natural disasters, they
      may be best understood as a dyad. APIM analyses provide new evidence suggesting a
      unidirectional path of influence from parents' disaster-related symptomatology to
      children's general mental health. Dyadic approaches to understanding mental
      health and treating symptoms of distress among disaster survivors and their
      families following trauma are encouraged. 

PMID- 25851240
TI  - Spirituality and/or religious faith: A means for coping with the effects of
      amyotrophic lateral sclerosis/motor neuron disease?
AB  - OBJECTIVE: The notion of spirituality/religious belief is recognized
      internationally as a domain within end-of-life care and is important in patients'
      and carers' quality-of-life. When faced with incurable illness, patients often
      become more philosophical about their life; many seek comfort in spiritual or
      religious philosophies. Our intention was to understand how personal spirituality
      and religious faith might help those living with amyotrophic lateral
      sclerosis/motor neuron disease (ALS/MND) cope with their impending death. METHOD:
      Unsolicited narratives (internet and print-published) written by individuals
      diagnosed with the terminal condition of ALS/MND were analyzed thematically.
      Narratives from 161 individuals diagnosed with ALS/MND written over a period of
      37 years (from 1968 to 2005) were included. RESULTS: Our findings reveal that
      religious faith sustains and helps people to avoid despair, and personal
      spirituality helps them make sense of what is happening to them. SIGNIFICANCE OF
      RESULTS: The use of personal narratives by people with ALS/MND has provided a
      vehicle for sharing their deepest spiritual and religious thoughts with others.
      The place of spirituality and religious faith within ALS/MND care should not be
      underestimated. Assessment of religious or spiritual needs should become a
      routine part of practice and is the responsibility of all members of the
      multidisciplinary team.

PMID- 25851239
TI  - The Potential Utility of Eye Movements in the Detection and Characterization of
      Everyday Functional Difficulties in Mild Cognitive Impairment.
AB  - Mild cognitive impairment (MCI) refers to the intermediate period between the
      typical cognitive decline of normal aging and more severe decline associated with
      dementia, and it is associated with greater risk for progression to dementia.
      Research has suggested that functional abilities are compromised in MCI, but the
      degree of impairment and underlying mechanisms remain poorly understood. The
      development of sensitive measures to assess subtle functional decline poses a
      major challenge for characterizing functional limitations in MCI. Eye-tracking
      methodology has been used to describe visual processes in everyday, naturalistic
      action among healthy older adults as well as several case studies of severely
      impaired individuals, and it has successfully differentiated healthy older adults
      from those with MCI on specific visual tasks. These studies highlight the promise
      of eye-tracking technology as a method to characterize subtle functional decline
      in MCI. However, to date no studies have examined visual behaviors during
      completion of naturalistic tasks in MCI. This review describes the current
      understanding of functional ability in MCI, summarizes findings of eye-tracking
      studies in healthy individuals, severe impairment, and MCI, and presents future
      research directions to aid with early identification and prevention of functional
      decline in disorders of aging. 

PMID- 25851241
TI  - Prevalence of polymorphisms with significant resistance to NS5A inhibitors in
      treatment-naive patients with hepatitis C virus genotypes 1a and 3a in Sweden.
AB  - BACKGROUND: The future treatment of hepatitis C virus (HCV) infection will be
      combinations of direct-acting antivirals (DAAs) that not only target multiple
      viral targets, but are also effective against different HCV genotypes. Of the
      many drug targets in HCV, one promising target is the non-structural 5A protein
      (NS5A), against which inhibitors, namely daclatasvir, ledipasvir and ombitasvir,
      have shown potent efficacy. However, since HCV is known to have very high
      sequence diversity, development of resistance is a problem against but not
      limited to NS5A inhibitors (i.e. resistance also found against NS3-protease and
      NS5B non-nucleoside inhibitors), when used in suboptimal combinations.
      Furthermore, it has been shown that natural resistance against DAAs is present in
      treatment-naive patients and such baseline resistance will potentially complicate
      future treatment strategies. METHODS: A pan-genotypic population-sequencing
      method with degenerated primers targeting the NS5A region was developed. We have
      investigated the prevalence of baseline resistant variants in 127 treatment-naive
      patients of HCV genotypes 1a, 1b, 2b and 3a. RESULTS: The method could
      successfully sequence more than 95% of genotype 1a, 1b and 3a samples.
      Interpretation of fold resistance data against the NS5A inhibitors was done with
      the help of earlier published phenotypic data. Baseline resistance variants
      associated with high resistance (1000-50,000-fold) was found in three patients:
      Q30H or Y93N in genotype 1a patients and further Y93H in a genotype 3a patient.
      CONCLUSION: Using this method, baseline resistance can be examined and the data
      could have a potential role in selecting the optimal and cost-efficient treatment
      for the patient.

PMID- 25851242
TI  - Seroprevalence of Toxoplasma gondii in Western Romania.
AB  - Toxoplasma gondii is an obligate intracellular parasite that most commonly causes
      asymptomatic infection in immunocompetent hosts, but can have devastating
      consequences in congenitally infected infants and immunocompromised patients. We
      evaluated the seroprevalence of T. gondii in the general population in Western
      Romania. Sera from 304 individuals were analysed with the Pastorex Toxo test,
      which allows the simultaneous detection of T. gondii IgG and/or IgM antibodies.
      T. gondii antibodies were demonstrated in 197 individuals (64.8%) and the
      prevalence increased with age: 35.0% in those < 20 years versus 76.8% in those >=
      70 years (p < 0.001). There was a higher prevalence of T. gondii antibodies in
      rural areas (76.9%) than in urban regions (55.3%) (p < 0.001). Our results
      suggest a high prevalence of T. gondii antibodies in Western Romania. 

PMID- 25851243
TI  - Patterns of outpatient ceftriaxone use in a Japanese general hospital: an
      increased need for development of outpatient parenteral antimicrobial therapy
      programs.

PMID- 25851244
TI  - Ventilator-associated pneumonia rates after introducing selective digestive tract
      decontamination.
AB  - The incidence of ventilator-associated pneumonia (VAP) before and after the
      introduction of selective oral decontamination (SOD) only and selective digestive
      tract decontamination (SDD) in a general intensive care population was examined.
      SOD as standard of care was introduced in December 2010 and SDD, including SOD,
      in January 2012 for all patients with an expected length of intensive care unit
      (ICU) stay of at least 48 h. The diagnosis of VAP was based on clinical criteria
      and quantitative cultures of bronchoalveolar lavage fluid. A total of 4945
      mechanically ventilated patients accounting for 37 554 ventilator days in the
      period from 2005 to 2013 were analyzed. The incidence of VAP per 1000 ventilator
      days declined significantly from 4.38 +/- 1.64 before to 1.64 +/- 0.43 after
      introduction of SOD/SDD (p = 0.007). Implementation of SOD/SDD as standard of
      care in ICUs may thus be effective in preventing VAP. 

PMID- 25851245
TI  - The voices of breastfeeding resource nurses.
AB  - OBJECTIVE: To describe and evaluate the Breastfeeding Resource Nurse (BRN) role
      and program at The Children's Hospital of Philadelphia (CHOP). DESIGN: The
      primary study was a multimethod study including a survey and key informant
      interviews to meet the study's objectives: to describe how the BRN implements his
      or her role at the unit level throughout the hospital, to describe the successes
      and challenges of the BRN role, to provide data on how BRNs may be better
      supported in their roles, and provide data for the translation of the BRN program
      to other institutions. We present the qualitative descriptive component from the
      primary study. SETTING: The Children's Hospital of Philadelphia enterprise.
      PARTICIPANTS: Eighteen BRNs within the CHOP enterprise. METHODS: Semistructured
      interviews were conducted with the BRN participants. The data were analyzed with
      conventional content analysis. RESULTS: Four major themes emerged from the BRN
      interview data: Empowering through evidence, Advocacy, Going the extra mile, and
      Personal connections to breastfeeding. CONCLUSIONS: Compelling stories
      illustrated the role of the BRN as patient advocate and educator for staff and
      families. Knowing the evidence about lactation and breastfeeding empowered the
      BRN to be successful in his or her role. The BRNs derived great personal and
      professional satisfaction from their roles. The BRN program can be easily adapted
      to other pediatric care centers and will enable improved breastfeeding outcomes
      at the point of care.

PMID- 25851248
TI  - The 'warm' side of coldness: Cold promotes interpersonal warmth in negative
      contexts.
AB  - The concrete experience of physical warmth has been demonstrated to promote
      interpersonal warmth. This well-documented link, however, tells only half of the
      story. In the current study, we thus examined whether physical coldness can also
      increase interpersonal warmth under certain circumstances. We conducted three
      experiments to demonstrate that the relationship between the experience of
      physical temperature and interpersonal outcomes is context dependent. Experiment
      1 showed that participants touching cold (vs. warm) objects were more willing to
      forgive a peer's dishonest behaviour. Experiment 2 demonstrated the fully
      interactive effect of temperature and context on interpersonal warmth:
      Participants touching cold (vs. warm) objects were less likely to assist an
      individual who had provided them with good service (positive social context), but
      more likely to assist an individual who had provided them with poor service
      (negative social context). Experiment 3 replicated the results of Experiment 2
      using the likelihood to complain, a hostility-related indicator, as the dependent
      variable: In a pleasant queue (positive social context), participants touching
      cold objects were more likely to complain and those touching warm objects were
      less likely to complain compared with the control group. This pattern was
      reversed in an annoying queue (negative social context). 

PMID- 25851249
TI  - Impact of residual (18)F-fluoride in (18)F-FDOPA for the diagnosis of
      neuroblastoma.
AB  - OBJECTIVE: PET imaging with (18)F-FDOPA has been successfully applied in the
      diagnosis and surveillance of neuroblastoma (NB) by targeting the overexpression
      of aromatic L-amino acid decarboxylase. This study aims to assess the impact of
      residual (18)F-fluoride on (18)F-FDOPA PET in NB and to implement a method to
      maintain low (18)F-fluoride content in future studies. METHODS: Automatic
      synthesis of (18)F-FDOPA was based on the electrophilic method using TRACERlab
      FXFE module. Radio-TLC was employed to determine residual (18)F-fluoride levels.
      We analyzed the impact of residual (18)F-fluoride on the images of 35 patients
      undergoing (18)F-FDOPA PET at initial diagnosis and/or follow-ups of NB. RESULTS:
      In 35 batches of (18)F-FDOPA products from 9/28/2010 to 07/27/2011, the mean
      residual (18)F-fluoride level was 4.4 % (range 0.2-19.1 %). Residual (18)F
      fluoride level >=4.0 % was associated with dense uptake in the growth plates,
      skull, and pelvis on PET scans, which may interfere with the interpretation of
      (18)F-FDOPA imaging in NB. By applying stringent restraints in (18)F-FDOPA
      production, including regular renewal of reagents, exclusive use  of NH4OH, and
      timely replacement of HPLC column, the incidence of (18)F-FDOPA batches with
      residual (18)F-fluoride level >=4.0 % was reduced from 33 to 4 % (P < 0.0001)
      during 7/30/2011-4/29/2013. CONCLUSION: By monitoring residual (18)F-fluoride
      levels and keeping stringent restraint procedures, low (18)F-fluoride content was
      achieved in most batches of (18)F-FDOPA, which diminished false-positive skeletal
      uptake. An appropriate upper limit of (18)F-fluoride level is suggested to be
      included in the criteria of routine quality control of (18)F-FDOPA productions.

PMID- 25851247
TI  - Carboxypeptidase B2 deficiency reveals opposite effects of complement C3a and C5a
      in a murine polymicrobial sepsis model.
AB  - BACKGROUND AND OBJECTIVES: Carboxypeptidase B2 (CPB2) is a basic carboxypeptidase
      with fibrin and complement C3a and C5a as physiological substrates. We
      hypothesized that in polymicrobial sepsis, CPB2-deficient mice would have
      sustained C5a activity, leading to disease exacerbation. METHODS: Polymicrobial
      sepsis was induced by cecal ligation and puncture (CLP). RESULTS: Contrary to our
      hypothesis, Cpb2(-/-) mice had significantly improved survival, with reduced lung
      edema, less liver and kidney damage, and less disseminated intravascular
      coagulation. Hepatic pro-CPB2 was induced by CLP, leading to increased pro-CPB2
      levels. Thrombomodulin present on mesothelium supported thrombin activation of
      pro-CPB2. Both wild-type and Cpb2(-/-) animals treated with a C5a receptor
      antagonist had improved survival, demonstrating that C5a was detrimental in this
      model. Treatment with a fibrinolysis inhibitor, tranexamic acid, caused a
      decrease in survival in both genotypes; however, the Cpb2(-/-) animals retained
      their survival advantage. Administration of a C3a receptor antagonist exacerbated
      the disease in both wild-type and Cpb2(-/-) mice and eliminated the survival
      advantage of Cpb2(-/-) mice. C5a receptor is expressed in both peritoneal
      macrophages and neutrophils; in contrast, C3a receptor expression is restricted
      to peritoneal macrophages, and C3a induced signaling in macrophages but not
      neutrophils. CONCLUSIONS: While C5a exacerbates the peritonitis, resulting in a
      deleterious generalized inflammatory state, C3a activation of peritoneal
      macrophages may limit the initial infection following CLP, thereby playing a
      diametrically opposing protective role in this polymicrobial sepsis model.

PMID- 25851250
TI  - Gonadotropin-releasing hormone receptor-targeted paclitaxel-degarelix conjugate:
      synthesis and in vitro evaluation.
AB  - To increase the selectivity of chemotherapeutic agents, receptor-mediated tumor
      targeting approaches have been developed. Here, degarelix [Ac-D-Nal-D-Cpa-D-Pal
      Ser-Aph(L-Hor)-D-Aph(Cbm)-Leu-ILys-Pro-D-Ala-NH2], a gonadotropin-releasing
      hormone antagonist, was employed as a targeting moiety for paclitaxel (PTX). Five
      PTX-degarelix conjugates were synthesized, in which PTX was attached via
      disulfide bond to the different position in the degarelix sequence. All of the
      PTX-degarelix conjugates exhibited a half-life greater than 10 h determined in
      human serum. A fluorometric imaging plate reader assay showed that the conjugates
      LK-MY-9 and LK-MY-10 had an antagonism efficacy similar to that of degarelix. The
      in vitro cytostatic effects of the conjugates were determined by a (3-(4,5
      dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H
      tetrazolium) (MTS) assay, and the 50% inhibitory concentration value of the
      conjugates on 3T3 mouse embryonic fibroblast cells were one order of magnitude
      higher than the 50% inhibitory concentration values of the conjugates on MCF-7
      human breast cancer cells and HT-29 human colon cancer cells. Receptor saturation
      tests further demonstrated that pre-incubation of the cells with degarelix
      reduced the efficacy of LK-MY-10 in a concentration-dependent manner. In
      conclusion, degarelix is a valid and stable moiety that has great potential for
      targeting chemotherapy drugs.

PMID- 25851251
TI  - Development and optimisation of 3-Acetyl-11-keto-beta-boswellic acid loaded poly
      lactic-co-glycolic acid-nanoparticles with enhanced oral bioavailability and in
      vivo anti-inflammatory activity in rats.
AB  - OBJECTIVES: 3-Acetyl-11-keto-beta-boswellic acid (AKBA) is a potent anti
      inflammatory compound of Boswellia serrata. However, anti-inflammatory activity
      of AKBA is impeded by poor oral bioavailability due to its poor aqueous
      solubility. In this context, we aimed to develop poly lactic-co-glycolic acid
      (PLGA)-based nanoparticle formulation of AKBA (AKBA-NPs) in order to improve its
      oral bioavailability and in-vivo anti-inflammatory activity in rats. METHODS:
      AKBA-NPs were prepared and characterised by analysing particle size and zeta
      potential using zeta sizer, surface morphology by scanning electron microscopy
      and transmission electron microscopy, and physical property using differential
      scanning calorimetry and X-ray diffraction techniques. The optimised
      nanoparticles were evaluated for in-vitro drug release and oral bioavailability
      studies, and in-vivo anti-inflammatory activity by carrageenan-induced rat paw
      oedema method. KEY FINDINGS: The optimised AKBA-NPs showed the particle size of
      179.6 nm with 0.276 polydispersity index and entrapment efficiency of 82.5%. AKBA
      NPs showed increased in-vivo anti-inflammatory activity as compared with AKBA.
      Bioavailability study revealed about six times higher peak plasma concentration
      of AKBA in AKBA-NPs. Moreover, t1/2 and total area under the curve of AKBA were
      also enhanced by two and ninefold, respectively, in AKBA-NPs as compared with
      corresponding AKBA. CONCLUSIONS: The promising results of improved oral
      bioavailability and in-vivo anti-inflammatory activity of AKBA suggested the
      successful nanoparticle formulation of AKBA.

PMID- 25851252
TI  - Palladium-Catalyzed Dynamic Kinetic Asymmetric Transformation of Racemic Biaryls:
      Axial-to-Central Chirality Transfer.
AB  - The first dynamic kinetic asymmetric transformation of racemic biaryl substrates
      on the basis of axial-to-central chirality transfer has been realized. Chiral Pd
      NHC complexes were found to catalyze the dynamic kinetic asymmetric
      spiroannulation of 4-(2-bromoaryl)-naphthalen-1-ols (or 2'-bromo-[1,1'-biphenyl]
      4-ols) with internal alkynes, affording a series of enantioenriched spirocyclic
      products bearing an all-carbon quaternary stereocenter in good yields (up to 95%)
      with excellent enantioselectivities (up to 97% ee). 

PMID- 25851253
TI  - Invited Editorial: MERS-CoV An Emerging Viral Zoonotic Disease: Three Years After
      and Counting.

PMID- 25851254
TI  - Chikungunya, the 2014, emerging infectious diseases in the Americas.

PMID- 25851255
TI  - Malaria by Plasmodium knowlesi, A Zoonosis Transmitted by Vectors.

PMID- 25851257
TI  - Frequency and clinical relevance of inconsistent code status documentation.
AB  - BACKGROUND: Accurate and complete documentation of hospitalized patients' code
      status is important to ensure that healthcare providers take appropriate action
      in the event of a cardiac arrest. OBJECTIVE: Determine the frequency and clinical
      relevance of incomplete and inconsistent code status documentation. DESIGN: Point
      prevalence study. SETTING: Academic medical centers. PATIENTS: Patients admitted
      to general internal medicine wards. MEASUREMENTS: Frequency and clinical
      relevance of inconsistent code status documentation across 5 documentation
      sources. RESULTS: Thirty-eight (20%; 95% confidence interval [CI], 14%-26%) of
      187 patients had complete and consistent code status documentation. Another 27
      (14%; 95% CI, 9%-19%) patients had no code status documentation. The remaining
      122 (65%; 95% CI, 58%-72%) patients had at least 1 code status documentation
      inconsistency. Of these, 38 (20%; 95% CI, 14%-26%) patients had a clinically
      relevant code status documentation inconsistency. Multivariate logistic
      regression analysis demonstrated that increased age (odds ratio [OR] = 1.07 [95%
      CI, 1.05-1.10] for every 1-year increase in age, P < 0.001) and patients
      receiving comfort measures (OR = 9.39 [95% CI, 1.35-65.19], P = 0.02) were
      independently associated with a clinically relevant code status documentation
      inconsistency. CONCLUSIONS: Incomplete and inconsistent documentation of code
      status occurred frequently in hospitalized patients, especially elderly patients
      and patients receiving comfort measures. Having multiple, poorly integrated code
      status documentation sources leads to a significant number of concerning
      inconsistencies that create opportunities for healthcare providers to
      inappropriately deliver or withhold resuscitative measures that conflict with
      patients' expressed wishes. Institutions need to be aware of this potential
      documentation hazard and take steps to minimize code status documentation
      inconsistencies.

PMID- 25851258
TI  - Effect of commercial starter cultures on volatile compound profile and sensory
      characteristics of dry-cured foal sausage.
AB  - BACKGROUND: The present work deals with the evaluation of the effect of three
      different commercial starter cultures (Chr. Hansen, Horsholm, Denmark) on the
      volatile compound profile and sensory properties, as well as some important
      physicochemical parameters, of dry-fermented foal sausages at the end of ripening
      in order to select the most suitable starter culture for this elaboration. The
      sausage batches were named as follows: CO (non-inoculated control), FS
      (Lactobacillus sakei + Staphylococcus carnosus), SM (L. sakei + S. carnosus +
      Staphylococcus xylosus + Pediococcus pentosaceus + Debaryomyces hansenii) and TR
      (L. sakei + S. carnosus +S. xylosus). RESULTS: The pH values differed
      significantly among batches, with the highest values corresponding to CO followed
      by TR, SM and FS. The highest amounts of volatile compounds were found in FS
      batch. Hexanal was the most abundant compound, especially in FS and SM batches.
      These batches also showed higher levels of compounds derived from carbohydrate
      fermentation and amino acid catabolism. Sensory results showed that acid taste
      was significantly lower in CO batch than in inoculated batches. CONCLUSION:
      According to most parameters, batches inoculated with FS and SM starters showed
      marked acidity compared with TR and CO batches, as expected from the
      manufacturer's indications. Therefore the most suitable starter culture for use
      in the manufacture of foal sausages in Mediterranean countries such as Spain with
      a preference for low-acidity products was found to be TR culture.

PMID- 25851259
TI  - The Uptake of GABA in Trypanosoma cruzi.
AB  - Gamma aminobutyric acid (GABA) is widely known as a neurotransmitter and signal
      transduction molecule found in vertebrates, plants, and some protozoan organisms.
      However, the presence of GABA and its role in trypanosomatids is unknown. Here,
      we report the presence of intracellular GABA and the biochemical characterization
      of its uptake in Trypanosoma cruzi, the etiological agent of Chagas' disease.
      Kinetic parameters indicated that GABA is taken up by a single transport system
      in pathogenic and nonpathogenic forms. Temperature dependence assays showed a
      profile similar to glutamate transport, but the effect of extracellular cations
      Na(+) , K(+) , and H(+) on GABA uptake differed, suggesting a different uptake
      mechanism. In contrast to reports for other amino acid transporters in T. cruzi,
      GABA uptake was Na(+) dependent and increased with pH, with a maximum activity at
      pH 8.5. The sensitivity to oligomycin showed that GABA uptake is dependent on ATP
      synthesis. These data point to a secondary active Na(+) /GABA symporter energized
      by Na(+) -exporting ATPase. Finally, we show that GABA occurs in the parasite's
      cytoplasm under normal culture conditions, indicating that it is regularly taken
      up from the culture medium or synthesized through an still undescribed metabolic
      pathway. 

PMID- 25851260
TI  - (1->3)-beta-D-glucan and galactomannan testing for the diagnosis of fungal
      peritonitis in peritoneal dialysis patients, a pilot study.
AB  - Fungal peritonitis is an uncommon but serious complication of peritoneal dialysis
      (PD) due to the fact that routine culture to recovered the etiologic agents are
      time consuming and KOH staining has very low sensitivity. Peritoneal (1->3)-beta
      D-glucan (BG) or galactomannan (GM), both fungal cell wall components, are
      candidate biomarkers of fungal peritonitis. Hence, a comparative cross-sectional
      analysis of peritoneal dialysis fluid (PDF) BG (Fungitell, Cape Cod, MA, USA) and
      GM (Platelia Aspergillus Ag kits, Bio-rad, France) from all PD patients with and
      without fungal peritonitis (13 cases, identified by culture), over a 1 year
      period, was performed. PDF of the fungal peritonitis group showed very high BG
      (494 +/- 19 pg/ml) and high GM (3.41 +/- 1.24) similar results were noted in
      specimens from cases of peritonitis with other causes, especially gram negative
      bacterial peritonitis. A BG cut-off value at 240 pg/ml and GM at 0.5 showed
      sensitivity/ specificity at 100%/ 83% and 77%/ 58%, respectively. A concomitantly
      positive GM reduced the false positive rate of BG from nonfungal peritonitis. In
      conclusion, BG and GM in peritoneal fluid with provisional cut-off values were
      applicable as surrogate biomarkers for the diagnosis of fungal peritonitis in PD
      patients. 

PMID- 25851261
TI  - MALDI-TOF MS-based identification of black yeasts of the genus Exophiala.
AB  - In this study, we investigated the applicability of matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) for the
      identification of Exophiala species. The analysis included a total of 110
      Exophiala isolates, including 15 CBS strains representing 4 species, Exophiala
      dermatitidis (61), E. phaeomuriformis (36), E. crusticola (9), and E.
      heteromorpha (4), that had been previously identified based on internal
      transcribed spacer (ITS) regions. We also compared the relative efficacies of
      Sabouraud glucose agar (SGA) and Columbia agar (CA) for use in MALDI-TOF MS.
      Remarkably, we obtained a log-score value >=2.0 by using either SGA or CA for all
      15 CBS strains, indicating species-level identification. The remaining 95
      Exophiala strains were identified to the genus or species levels, with
      identification rates of 96.8% and 90.5%, using SGA or CA, respectively. Most of
      the E. dermatitidis (100% and 92.9%), E. phaeomuriformis (80.6% and 83.9%), E.
      crusticola (50% and 100%), and E. heteromorpha (100% and 100%) isolates were
      correctly identified using SGA or CA, respectively. Furthermore, 58.9% and 26.3%
      of the strains had log-score values of >=2.0 by using SGA and CA, respectively.
      Our results indicate that MALDI-TOF MS is a rapid and reliable technique with
      high rates of correct taxonomic identification. 

PMID- 25851262
TI  - Genome sequence comparison of Aspergillus fumigatus strains isolated from
      patients with pulmonary aspergilloma and chronic necrotizing pulmonary
      aspergillosis.
AB  - Aspergillus fumigatus is the Aspergillus species most commonly associated with
      aspergillosis. Of the various presentations of aspergillosis, one of the most
      frequently observed in cases involving A. fumigatus pulmonary infections is
      aspergilloma (PA). In such infections one finds a fungus ball composed of fungal
      hyphae, inflammatory cells, fibrin, mucus, and tissue debris. Chronic necrotizing
      pulmonary aspergillosis (CNPA), also known as semi-invasive or invasive
      aspergillosis, is locally invasive and predominantly seen in patients with mild
      immunodeficiency or with a chronic lung disease. In the present study, with the
      aid of a next-generation sequencer, we conducted whole genome sequence (WGS)
      analyses of 17 strains isolated from patients in Japan with PA and CNPA. A total
      of 99,088 SNPs were identified by mapping the reads to A. fumigatus genome
      reference strain Af293, and according to genome-wide phylogenetic analysis, there
      were no correlations between the whole genome sequence typing results and
      pathologic conditions of patients. Here, we conducted the first multi-genome WGS
      study to focus on the A. fumigatus strains isolated from patients with PA and
      CNPA, and comprehensively characterized genetic variations of strains. WGS
      approach will help in better understanding of molecular mechanisms of
      aspergillosis cases caused by A. fumigatus. 

PMID- 25851263
TI  - First report of Veronaea botryosa as a causal agent of chromomycosis in frogs.
AB  - A dematiaceous hyphomycete, isolated from frogs, was determined as the possible
      etiologic agent of a case of systemic chromomycosis this cold-blooded animal. The
      fungus was identified as Veronaea botryosa on the basis of morphological features
      observed in histopathological examination and molecular phylogenetic evidence.
      Although V. botryosa is known to be distributed widely in litter and as a human
      pathogen, this is the first confirmed report of its involvement in a lethal
      infection in a cold-blooded animal, including an anuran. 

PMID- 25851264
TI  - Efficacy of Ethanol against Trichosporon asahii Biofilm in vitro.
AB  - Trichosporon asahii (T. asahii) can cause invasive infections, particularly
      catheter-related bloodstream infections (CR-BSIs). T. asahii biofilm, which is
      resistant to the most common clinical antifungal agents, may play an important
      role in these life-threatening infections. This study focused on the effects of
      ethanol on the different phases of T. asahii biofilm formation. At the
      concentrations clinically used, ethanol killed T. asahii planktonic cells (MIC90
      = 15% and m-MIC90 = 15%) and biofilm (SMIC90 = 50%), and exposure to 25% ethanol
      for 12 h or to 50% ethanol for 8 h completely inhibited biofilm development and
      eradicated mature T. asahii biofilm. Thus, our results showed that ethanol
      effectively inhibited the main phases of T. asahii biofilm formation. This study
      reveals a new potential strategy to prevent and treat T. asahii biofilm-related
      CR-BSIs. 

PMID- 25851266
TI  - Do anti-hypertensive renin-angiotensin system inhibitors contribute to the
      development of classical Kaposi sarcoma?

PMID- 25851265
TI  - Cytotoxic effects of aflatoxin B1 on human brain microvascular endothelial cells
      of the blood-brain barrier.
AB  - Aflatoxins are mycotoxins produced by Aspergillus spp. Although AFB1 is
      implicated as a carcinogen in hepatocellular carcinoma, brain autopsies in
      affected areas have revealed its presence in 81% of cases. Given its
      haematogenous spread, here we determined the cytotoxic effects of AFB1 on primary
      human brain microvascular endothelial cells (HBMEC), which constitute the blood
      brain barrier, human umbilical vein endothelial cells (HUVEC) as well as
      immortalized epithelial cells of human hepatocellular carcinoma (Huh7). The cell
      types were exposed to AFB1 (3-32 nM) for 24 h and release of lactate
      dehydrogenase was measured as cell cytotoxicity marker. Furthermore, DNA was
      collected from both cell types and DNA adduct formation was determined by
      immunoblot using anti-AFB1-DNA adduct antibody. At 32 nM, AFB1 killed >85% HBMEC,
      while controls showed minimal effects (P < .05). Similar concentrations of AFB1
      showed 22% cell death of HUVEC, while the same concentration did not kill Huh7.
      At low concentrations, in other words, 3.2 nM, AFB1 produced DNA adduct formation
      in HBMEC, while high concentration (32 nM) did not form DNA adducts. For HUVEC,
      16 nM and 32 nM exhibited DNA adduct formation. For Huh7, 3.2 nM did not form DNA
      adducts, while 32 nM exhibited DNA adduct formation. For the first time, we
      report that AFB1 affected the viability of primary endothelial cells but not
      immortalized Huh7 cells. Cytotoxicity of brain endothelial cells suggests extra
      hepatic complications post-AFB1 exposure. 

PMID- 25851267
TI  - Diet and cognitive decline at middle age: the role of antioxidants.
AB  - To assess the relationship between dietary intake of antioxidants (vitamin C,
      vitamin E, beta-carotene, lutein, flavonoids and lignans) and cognitive decline
      at middle age, analyses were performed on data from the population based
      Doetinchem Cohort Study. Habitual diet and cognitive function were assessed twice
      with a 5-year interval in 2613 persons aged 43-70 year at baseline (1995-2002).
      Diet was assessed with a validated 178-item semi-quantitative FFQ. Cognitive
      function was assessed with a neuropsychological test battery, consisting of the
      15 Words Learning Test, the Stroop Test, the Word Fluency test, and the Letter
      Digit Substitution Test. Scores on global cognitive function, memory, processing
      speed, and cognitive flexibility were calculated. In regression analyses,
      quintiles of antioxidant intake were associated with change in cognitive domain
      scores. Results showed that higher lignan intake was linearly associated with
      less decline in global cognitive function (P= 0.01), memory (P< 0.01) and
      processing speed (P= 0.04), with about two times less declines in the highest v.
      the lowest quintile. In the lowest quintile of vitamin E intake, decline in
      memory was twice as fast as in all higher quintiles (P< 0.01). Global cognitive
      decline in the highest lutein intake group was greater than in the lowest intake
      group (P< 0.05). Higher flavonoid intake was associated with greater decline in
      cognitive flexibility (P for trend = 0.04). Intakes of other antioxidants were
      not associated with cognitive decline. We conclude that within the range of a
      habitual dietary intake, higher intake of lignans is associated with less
      cognitive decline at middle age.

PMID- 25851268
TI  - Antibiotics for asymptomatic bacteriuria.
AB  - BACKGROUND: Asymptomatic bacteriuria is commonly detected in women aged up to 60
      years, patients with diabetes, and the elderly. The benefit of antibiotic
      treatment for this condition is controversial. OBJECTIVES: To assess the
      effectiveness and safety of antibiotics treatment for asymptomatic bacteriuria in
      adults. Specific objectives were to assess 1) the effectiveness of antibiotics
      for preventing development of symptomatic UTI, UTI-related complications, overall
      mortality, UTI-related mortality, and resolution of bacteriuria; 2) the
      development of resistance to antibiotic treatment by comparing resistance of
      grown bacteria in urine before and after therapy; and 3) the frequency of adverse
      events. SEARCH METHODS: We searched the Cochrane Renal Group's Specialised
      Register up to 24 February 2015 through contact with the Trials' Search Co
      ordinator using search terms relevant to this review. SELECTION CRITERIA:
      Randomised controlled trials (RCTs) and quasi-RCTs comparing antibiotics to
      placebo or no treatment for asymptomatic bacteriuria in adults were included. The
      outcomes of interest were the development of symptomatic urinary tract infection
      (UTI), complications, death, any adverse event, development of antibiotic
      resistance, bacteriological cure, and decline in kidney function. DATA COLLECTION
      AND ANALYSIS: Two authors independently extracted the data and assessed study
      quality. Statistical analyses were performed using the random effects model and
      the results expressed as risk ratios (RR) with 95% confidence intervals (CI).
      MAIN RESULTS: We included nine studies (1614 participants) in this review.
      Symptomatic UTI (RR 1.11, 95% CI 0.51 to 2.43), complications (RR 0.78, 95% CI 0.
      35 to 1.74), and death (RR 0.99, 95% CI 0.70 to 1.41) were similar between the
      antibiotic and placebo or no treatment arms. Antibiotics were more effective for
      bacteriological cure (RR 2.32, 95% CI 1.11 to 4.83) but also more adverse events
      developed in this group (RR 3.77, 95% CI 1.40 to 10.15). No decline in the kidney
      function was observed across the studies; minimal data were available on the
      emergence of resistant strains after antimicrobial treatment.The included studies
      were of medium and high quality, used different treatments for different
      durations of treatment and follow-up, different populations, but this did not
      appear to influence the results of review. AUTHORS' CONCLUSIONS: No differences
      were observed between antibiotics versus no treatment of asymptomatic bacteriuria
      for the development of symptomatic UTI, complications or death. Antibiotics were
      superior to no treatment for the bacteriological cure but with significantly more
      adverse events. There was no clinical benefit from treating asymptomatic
      bacteriuria in the studies included in this review.

PMID- 25851269
TI  - High tolerance and physiological mechanism of Zymomonas mobilis to phenolic
      inhibitors in ethanol fermentation of corncob residue.
AB  - Corncob residue as the lignocellulosic biomass accumulated phenolic compounds
      generated from xylitol production industry. For utilization of this biomass,
      Zymomonas mobilis ZM4 was tested as the ethanol fermenting strain and presented a
      better performance of cell growth (2.8 * 10(8)  CFU/mL) and ethanol
      fermentability (54.42 g/L) in the simultaneous saccharification and fermentation
      (SSF) than the typical robust strain Saccharomyces cerevisiae DQ1 (cell growth of
      2.9 * 10(7)  CFU/mL, ethanol titer of 48.6 g/L). The physiological response of Z.
      mobilis ZM4 to the twelve typical phenolic compounds derived from lignocellulose
      was assayed and compared with that of S. cerevisiae DQ1. Z. mobilis ZM4 showed
      nearly the same tolerance to the phenolic aldehydes with S. cerevisiae DQ1, but
      the stronger tolerance to the phenolic acids existing in corncob residue (2
      furoic acid, p-hydroxybenzoic acid, p-coumaric acid, vanillic acid, ferulic acid,
      and syringic acid). The tolerance mechanism of Z. mobilis was investigated in
      terms of inhibitor degradation, cell morphology and membrane permeability under
      the stress of phenolics using GC-MS, scanning and transmission electron
      microscopies (SEM and TEM), as well as fluorescent probes. The results reveal
      that Z. mobilis ZM4 has the capability for in situ detoxification of phenolic
      aldehydes, and the lipopolysaccharide aggregation on the cell outer membrane of
      Z. mobilis ZM4 provided the permeable barrier to the attack of phenolic acids.

PMID- 25851270
TI  - Microphase Structure, Crystallization Behavior, and Wettability Properties of
      Novel Fluorinated Copolymers Poly(perfluoroalkyl acrylate-co-stearyl acrylate)
      Containing Short Perfluorohexyl Chains.
AB  - Novel fluorinated copolymers of stearyl acrylate (SA) and (perfluorohexyl)ethyl
      acrylate (C6A), (perfluorohexyl)ethyl methacrylate (C6MA), 2-[[[[2
      (perfluorohexyl)]-sulfonyl]methyl] amino]ethyl acrylate (C6SA), and methacrylate
      (C6SMA) were synthesized via miniemulsion copolymerization. The extremely
      hydrophobic monomers perfluoroalkyl acrylate (FA) and SA acted as the reactive
      costabilizer in the miniemulsion system. The microstructure and surface wetting
      properties of the copolymers were characterized by (1)H NMR, FT-IR, and dynamic
      contact angle test. The crystallization behaviors and fine surface structures of
      the copolymer films were determined by differential scanning calorimetry (DSC)
      and wide-angle X-ray diffraction (WAXD) analysis. The self-assembled aggregation
      and roughness of the copolymer films were investigated by atomic force microscopy
      (AFM). The results showed that the fluorinated side chains interrupted and
      impeded the crystallizable side chains of SA from forming complete crystals. And
      the Tm and DeltaHf of the copolymers were decreased as a consequence of this
      effect. The fluorinated side chains in P(C6A/SA) and P(C6MA/SA) arranged between
      the crystallizable hydrocarbon side chains of SA, while the crystallization
      structure of fluorinated and nonfluorinated pendant groups existed all at once in
      copolymers P(C6SA/SA) and P(C6SMA/SA). The four copolymers exhibited very low
      surface free energy and excellent dynamic water repellency attributed to the
      restriction of perfluoroalkyl groups combined with crystallization of stearyl
      pendant groups. 

PMID- 25851271
TI  - Comparing long-term outcomes of primary and progressive carcinoma invading
      bladder muscle after radical cystectomy.
AB  - OBJECTIVE: To assess the impact of primary or progressive status on recurrence
      free survival (RFS), cancer-specific mortality (CSM) and overall mortality (OM)
      after radical cystectomy (RC) for muscle- invasive bladder cancer (MIBC).
      PATIENTS AND METHODS: A total of 768 consecutive patients underwent RC as
      treatment for MIBC at our institution between 2000 and 2012. Primary MIBC was
      defined as no previous history of bladder cancer and progressive was defined as
      recorded previous treated non-MIBC (NMIBC) that had progressed to MIBC. The
      median follow-up was 85 (60-109) months. Univariate and multivariate Cox
      regression models were used to compare RFS, CSM and OM between these two cohorts.
      RESULTS: In all, 475 (61.8%) patients had primary and 293 (38.2%) patients had
      progressive MIBC. There were no differences between the two groups in terms of
      demographics, pathological and peri-operative complications (all P > 0.1). The 10
      year RFS, CSM and OM rates for primary vs progressive status were 43 vs 36% (P =
      0.01), 43 vs 37% (P = 0.01), and 35 vs 28% (P = 0.03), respectively. On
      multivariable Cox regression analyses, progressive status remained significantly
      associated with a higher rate of recurrence (hazard ratio [HR] 1.47, 95%
      confidence interval [CI] 1.12-1.79; P = 0.03), CSM (HR 1.42, 95% CI 1.07-1.89; P
      = 0.01) and OM (HR1.42, 95% CI 1.13-1.65; P = 0.02). CONCLUSIONS: Among patients
      treated with RC for MIBC, progressive status was associated with a higher CSM, OM
      and recurrence rate after RC. The present study thus provides an impetus to
      improve risk sub-stratification when bladder cancer is still at the NMIBC stage,
      be it through new biomarkers or improved imaging, as a subset of patients with
      NMIBC are likely to benefit from early RC.

PMID- 25851272
TI  - Drinking resumption: problematic alcohol use relapse after rehabilitation. A
      phenomenological hermeneutical perspective.
AB  - The majority of patients being treated for alcohol abuse disorders experience one
      or more relapses after treatment. The fact that people use this inebriant in a
      way leading to so much harm and suffering might seem a conundrum. Therapists,
      family and others might find the person's relapse to be dramatic and upsetting,
      and one might question whether the person has the sufficient will or motivation
      to change. However, few previous studies have explored relapse from the patient's
      perspective. The aim of this study was to illuminate the patient's lived
      experience of relapse and to develop a deeper understanding of this phenomenon.
      The study consisted of qualitative interviews using a phenomenological
      hermeneutical approach. Three main themes emerged from the analyses: 'craving',
      'self-image' and 'time'. The findings were discussed in the context of
      phenomenological literature. Cravings could occur unpredictably; nevertheless,
      craving was a common experience for the patients and signified a risk of relapse.
      Bodily experiences of craving were frequently mentioned, and alcohol addiction
      could be understood as to be a disease or a learned habit. Self-image was, at
      times, adversely affected by relapse episodes. Therefore, feelings of shame, self
      respect and recognition were significant concepts. This study found that the
      perception of time as past, present and future greatly influenced the
      participants' experiences of relapse and rehabilitation. Thus, relapse was an
      upsetting and dramatic experience that could cause great discomfort and sometimes
      life-threatening situations. However, relapse could also be viewed as a planned
      event. This study highlights important truth and reality about alcoholism and
      relapse grounded in people's lived experience. 

PMID- 25851273
TI  - Heterobi- and -trimetallic Ion Pairs of Zirconocene-Based Isoselective Olefin
      Polymerization Catalysts with AlMe3.
AB  - The reactivity towards AlMe3 of discrete cationic ansa-zirconocenes 2 a,b that
      are ubiquitously used in isoselective propylene polymerization and based on
      [{Ph(H)C(3,6-tBu2-Flu)(3-tBu-5-Et-Cp)}ZrMe2)] {Cp-Flu} and rac-[{Me2Si-(2-Me-4-Ph
      Ind)2}ZrMe2] {SBI} was scrutinized. The first example of a structurally
      characterized Group 4 metallocene AlMe3 adduct (3 b) is reported. In the presence
      of excess AlMe3, the {SBI}-based AlMe3 adduct 3 b undergoes a slow decomposition
      via C-H activation in a bridging methyl unit to yield a new species (4 b) with a
      trimetallic {Zr(MU-CH2)(MU-Me)AlMe(MU-Me)AlMe2} core. EXSY NMR data for the
      process 2 b?3 b->4 b suggest very rapid and reversible binding of an additional
      AlMe3 molecule onto AlMe3 adduct 3 b. The resulting heterotrimetallic species
      intermediates exchange of methyl groups between different metal centers and
      slowly undergoes the C-H activation reaction towards 4 b.

PMID- 25851281
TI  - Sins of omission and commission in systematic reviews in nursing: A commentary on
      McRae et al. (2015).

PMID- 25851282
TI  - Efficacy of concurrent superselective intra-arterial chemotherapy and
      radiotherapy for late-stage squamous cell carcinoma of the temporal bone.

PMID- 25851283
TI  - A prediction model for colon cancer surveillance data.
AB  - Dynamic prediction models make use of patient-specific longitudinal data to
      update individualized survival probability predictions based on current and past
      information. Colonoscopy (COL) and fecal occult blood test (FOBT) results were
      collected from two Australian surveillance studies on individuals characterized
      as high-risk based on a personal or family history of colorectal cancer.
      Motivated by a Poisson process, this paper proposes a generalized nonlinear model
      with a complementary log-log link as a dynamic prediction tool that produces
      individualized probabilities for the risk of developing advanced adenoma or
      colorectal cancer (AAC). This model allows predicted risk to depend on a
      patient's baseline characteristics and time-dependent covariates. Information on
      the dates and results of COLs and FOBTs were incorporated using time-dependent
      covariates that contributed to patient risk of AAC for a specified period
      following the test result. These covariates serve to update a person's risk as
      additional COL, and FOBT test information becomes available. Model selection was
      conducted systematically through the comparison of Akaike information criterion.
      Goodness-of-fit was assessed with the use of calibration plots to compare the
      predicted probability of event occurrence with the proportion of events observed.
      Abnormal COL results were found to significantly increase risk of AAC for 1 year
      following the test. Positive FOBTs were found to significantly increase the risk
      of AAC for 3 months following the result. The covariates that incorporated the
      updated test results were of greater significance and had a larger effect on risk
      than the baseline variables.

PMID- 25851284
TI  - Heating-induced transition of Potyvirus Potato Virus A coat protein into beta
      structure.
AB  - In our previous communication, we have reported that virions of plant Potyvirus
      Potato Virus A (PVA) have a peculiar structure characterized by high content of
      disordered regions in intravirus coat protein (CP). In this report, we describe
      unusual properties of the PVA CP. With the help of a number of physicochemical
      methods, we have observed that the PVA CP just released from the virions by
      heating at 60-70  degrees C undergoes association into oligomers and transition
      to beta- (and even cross-beta-) conformation. Transition to beta-structure on
      heating has been recently reported for a number of viral and non-viral proteins.
      The PVA CP isolated by LiCl method was also transformed into cross-beta-structure
      on heating to 60  degrees C. Using the algorithms for protein aggregation
      prediction, we found that the aggregation-prone segments should be located in the
      central region of a PVA CP molecule. Possibly this transition mimics some
      functions of PVA CP in the virus life cycle in infected plants. 

PMID- 25851285
TI  - Renal impairment an impediment to heart transplantation?
AB  - Chronic kidney disease and chronic heart failure are now recognized as closely
      intertwined entities. The noxious interactions between the heart and kidney
      systems as part of the so-called cardiorenal syndrome is a matter of great
      concern for heart transplant candidates. Not only is chronic kidney disease a
      commonly associated comorbidity, but its detrimental effect on the outcome of
      heart transplantation is now well established. In the more advanced stages of
      kidney disease, it may even deter physicians from carrying out heart
      transplantation in potential candidates. This review offers insights on
      epidemiological issues regarding chronic kidney disease among patients awaiting
      heart transplantation as well as its impact on the outcomes related with heart
      transplantations. Finally, emerging therapeutic opportunities which may benefit
      heart transplant candidates with the most severe renal impairment will be
      reviewed with a special emphasis on combined heart-kidney transplantation.

PMID- 25851286
TI  - Immune disorders in hemodialysis patients.
AB  - Immunologically, End Stage renal Disease (ESRD) is associated with some disorders
      in both innate and adaptive immune system in such a form that there is a
      coexistence of both immune activation and immune suppression. Although these
      disorders are complex yet thoroughly unknown, there is a close relation between
      the progressively defective immune system with side effects as well as mortality
      causes including cardiovascular problems, infections, and malignancies. From the
      other point, chronic inflammation as a major determinant of "dialysis syndrome"
      (including malnutrition, cachexia, and vasculopathy) is considered as the main
      factor of inability and mortality in dialysis patients. Such inflammation is
      generally arisen from immune system response to uremia and individual's
      repetitive contact with dialysis instruments and, in the long term, leads to
      premature aging via intensifying tissue degeneration. Therefore, the immune
      system is known as one of the most important therapeutic targets to reduce
      morbidity and mortality in uremic and dialysis patients.   This review addresses
      different aspects as well as mechanisms of immune system dysfunction and possible
      therapeutics in dialysis patients. 

PMID- 25851287
TI  - Vitamin E as adjuvant treatment for urinary tract infection in girls with acute
      pyelonephritis.
AB  - INTRODUCTION: Vitamin E is a fat-soluble vitamin that functions as an
      antioxidant. The aim of this study was to investigate the effects of vitamins E
      supplementation in combination with antibiotics for the treatment of girls with
      acute pyelonephritis. MATERIALS AND METHODS: This double-blinded randomized
      controlled trial was conducted on 152 girls aged 5 to 12 years with a first acute
      pyelonephritis episode based on technetium Tc 99m dimercaptosuccinic acid (99mTc
      DMSA). They were randomized to receive a 14-day treatment with only antibiotics
      (control group; n = 76) and 14-day treatment with supplements of vitamin E
      (intervention group; n = 76) in addition to the antibiotics. Patients' clinical
      symptoms were monitored for 14 days and urine culture was performed 3 to 4 days
      and 7 to 10 days after the start of the treatment and its completion,
      respectively. All of the girls once underwent DMSA scan 4 to 6 months after the
      treatment. RESULTS: During the follow-up days, the mean frequency of fever (P =
      .01), urinary frequency (P = .001), urgency (P = .003), dribbling (P = .001), and
      urinary incontinence (P = .006) were significantly lower in the intervention
      group compared to the control group. There was no significant difference in the
      results of urine culture 3 to 4 days after the start of treatment (P = .16) and 7
      to 10 days after its termination (P = .37). There was also no significant
      difference between the results of DMSA scan 4 to 6 months after the start of
      treatment (P = .31). CONCLUSIONS: Vitamin E supplementation has a significant
      effect in ameliorating sign and symptoms of UTI. However, further studies are
      recommended to confirm these findings.

PMID- 25851288
TI  - Evaluation of Th17 pathway in the diagnosis of autosomal dominant polycystic
      kidney disease.
AB  - INTRODUCTION: Current assessment tools of autosomal dominant polycystic kidney
      disease (ADPKD) diagnosis are challenging. This study evaluated the possible
      application of assessment of interleukin (IL)-17-related cytokines and the
      circulatory T helper 17 cells in the diagnosis of ADPKD. MATERIALS AND METHODS:
      Enrolling 54 ADPKD patients and 54 healthy individuals, we measured serum and
      urine levels of IL-6, IL-17, IL-23, and transforming growth factor-beta and the
      peripheral blood frequency of T helper 17 cells through flowcytometry. We
      computed sensitivity and specificity of each inflammatory marker as well as their
      different combinations using the receiver operating characteristic curve and
      discriminant function analysis. RESULTS: The mean serum and urine levels of IL-17
      and IL-23 as well as urine levels of IL-6 were higher in ADPKD patients compared
      to the healthy controls (P < .001). There was no significant difference in the
      number of T helper 17 cells between the two groups. Among different combinations
      of the inflammatory markers, the serum IL-17 was the best factor in the diagnosis
      of ADPKD with a sensitivity as well as specificity of 100%. CONCLUSIONS: It is
      likely that T helper 17 pathway is involved in the pathogenesis of ADPKD;
      therefore, it may be beneficial if such a pathway be considered in its diagnosis.

PMID- 25851289
TI  - Incidence and complications of acute kidney injury following coronary artery
      bypass graft: a retrospective cohort study.
AB  - INTRODUCTION: Acute kidney injury (AKI) is a common complication of coronary
      artery bypass graft with several serious complications. This study aimed to find
      the incidence of AKI after coronary artery bypass graft and its complications
      based on the Acute Kidney Injury Network (AKIN) criteria. MATERIALS AND METHODS:
      This study was done on 3470 patients who had undergone isolated coronary artery
      bypass graft. Acute kidney injury's incidence was based on the AKIN criteria
      (only based on serum creatinine irrespective of urine output). Patients'
      demographic data, in-hospital complications, and out-hospital mortality were
      collected from hospital databases and compared between the patients with and
      without AKI. RESULTS: Based on serum creatinine, the incidence of AKI was 27.7%
      (958 patients) on the 1st postoperative day. Nine patients (0.3%) needed
      hemodialysis during their hospital stay, and 31 patients (0.7%) developed
      persistent kidney failure until the discharge day. The number of patients
      undergoing hemodialysis was not significantly difference but persistent kidney
      failure was significantly more frequent in patients with AKI (P < .001). Those
      with AKI also experienced longer length of stay (P = .04) and longer length of
      stay in intensive care unit (P < .001), and their mortality rate was higher in
      hospital (P < .001) and during the 3-year follow-up period (P < .001).
      CONCLUSIONS: Although AKI is associated with great patients' morbidity and in
      hospital and long-term mortality, most of AKI episodes after coronary artery
      bypass graft are mild with no need for hemodialysis, and they mostly improve
      spontaneously.

PMID- 25851290
TI  - Gene mutation analysis in Iranian children with nephronophthisis: a two-center
      study.
AB  - INTRODUCTION: Nephronophthisis is of the most commonly inherited ciliopathies
      that leads to end-stage renal disease in children. The NPHP1 gene is the first
      identified gene responsible for nephronophthisis and related diseases. This study
      assessed mutations of the NPHP1 gene in 16 Iranian families with at least one
      member presenting features of nephronophthisis. MATERIALS AND METHODS: Fifty
      seven patients diagnosed with chronic kidney disease or end-stage renal disease
      were referred to Imam Hossein Children Hospital, in Isfahan, Iran. The gene
      analysis study was carried on 16 patients and their first-degree relatives (40
      DNA samples) suspicious of having nephronophthisis. The NPHP1 deletion analysis
      was performed for exons 5, 7, and 20 of the NPHP1 gene. RESULTS: The patients'
      median age was 15 years. The mean and median age of the first presentation was
      10.06 +/- 2.59 years and 10.5 years, respectively. A homozygous deletion was
      identified in the NPHP1 gene spanning at least from exon 5 to exon 20 in two
      families. High-throughput mutation analysis identified a homozygous truncating
      mutation (c.1504C>T, p.R502*) in the NPHP5 in 5 families. CONCLUSIONS: By
      combining NPHP1 deletion analysis with multiplex-polymerase-chain-reaction-based
      high-throughput mutation analysis we could identify the molecular disease-cause
      in 7 of 15 families from Iran. In 8 families, the molecular disease cause
      remained unknown.

PMID- 25851291
TI  - Detection of an earlier tubulopathy in diabetic nephropathy among children with
      normoalbuminuria.
AB  - INTRODUCTION: Diabetic nephropathy is a major cause of morbidity and mortality
      among young adults with type 1 diabetes mellitus (DM). Albuminuria, the gold
      standard for early diagnosis, cannot always detect early diabetic nephropathy. We
      aimed at evaluating the level of urine neutrophil gelatinase-associated lipocalin
      (NGAL) as a marker of tubulointerstitial damage in children and adolescents with
      type 1 DM in relation to the level of albuminuria and other parameters. MATERIALS
      AND METHODS: Fifty children with type 1 DM for more than 5 years were included in
      this study (mean age, 13.8 +/- 4.0 years), and 18 healthy children served as
      controls. Patients with overt albuminuria (> 300 mg/g creatinine) or inflammatory
      states were excluded. Urine NGAL, microalbuminuria, and urine albumin-creatinine
      ratio were measured in patients and controls as well as other parameters.
      RESULTS: Urine NGAL was significantly higher in microalbuminuric in comparison
      with normoalbuminuric patients and controls, and correlated positively with urine
      albumin-creatinine ratio. A positive urine NGAL was observed in 12 of 38
      normoalbuminuric patients (31.6%) compared to 9 of 12 microalbuminuric patients
      (75%). A positive correlation was reported between urine NGAL and both Hemoglobin
      A1c and duration of DM, but not with estimated glomerular filtration rate or
      hypertension. CONCLUSIONS: Diabetic children, even some normoalbuminurics, showed
      increased urine NGAL. This finding may support the hypothesis of a "tubular
      phase" of diabetic disease preceding overt diabetic nephropathy, and hence, the
      use of urine NGAL measurement for early evaluation of renal involvement.

PMID- 25851292
TI  - Effects of lowering dialysate calcium concentration on mineral metabolism and
      hemodynamic parameters in hemodialysis patients.
AB  - INTRODUCTION: It has been suggested that a dialysate calcium concentration of 1.5
      mmol/L is a compromise between bone protection and cardiovascular risk. This
      study aimed to investigate the effect of reducing dialysate calcium concentration
      to 1.5 mmol/L on mineral metabolism and hemodynamic parameters. MATERIALS AND
      METHODS: Dialysate calcium concentration was changed from 1.75 mmol/L to 1.5
      mmol/L for 9 months and observed the effects on mineral metabolism and dialysis
      outcome parameters in 52 hemodialysis patients. RESULTS: The results at 9 months
      demonstrated that postdialytic serum calcium level decreased significantly from
      109 +/- 7 mg/L to 102 +/- 6 mg/L, intact parathyroid hormone (PTH) increased from
      372 +/- 52 pg/mL to 606 +/- 80 pg/mL, and the oral alfacalcidol increased from
      1.4 +/- 0.3 ug/w to 3.3 +/- 0.4 ug/w. In patients with low PTH levels, continuous
      increase of PTH was observed. There were no significant variation in the oral
      calcium carbonate dose and serum levels of alkaline phosphatase, predialytic
      calcium, and pre- and postdialytic phosphorus. The ultrafiltration rate and
      postdialysis systolic blood pressure were significantly lower after reducing the
      dialysate calcium concentration to 1.5 mmol/L. Intradialytic hypotension and
      cramps were more frequent with this dialysate calcium concentration. CONCLUSIONS:
      These findings demonstrated that a decrease in dialysate calcium concentration
      from 1.75 mmol/L to 1.5 mmol/L improved mineral metabolism by prevention of
      postdialytic hypercalcemia and releasing oversuppression of PTH, but it was
      associated with more use of oral alfacalcidol and more hemodynamic impairment.

PMID- 25851294
TI  - Soluble major histocompatibility complex class I chain-related antigen A level in
      chronic allograft dysfunction.
AB  - INTRODUCTION: Soluble major histocompatibility complex class I chain-related
      antigen A (soluble MICA) has recently been considered as an inhibitory molecule
      which is shed from tumors and protects them against natural killers and some
      subgroups of T cells' cytolysis. In transplantation, soluble MICA is also a
      foreign antigenic molecule that can induce allospecific responses. This study
      aimed to clarify its possible role in long-term kidney allograft outcome.
      MATERIALS AND METHODS: Thirty patients with biopsy-proven chronic allograft
      dysfunction (CAD) were pair-matched with kidney allograft recipients with 30
      stable graft function. Fifteen healthy individuals were enrolled as controls.
      Soluble MICA antigen and anti-HLA antibodies were measured in their serum.
      RESULTS: There was no significant difference between CAD patients, stable
      recipients, and healthy volunteers in frequency or titer of soluble MICA;
      however, soluble MICA-positive patients were more frequent in the stable group
      was than the CAD group (43.4% versus 33.3%). In addition, a high level of soluble
      MICA was accompanied by enhanced humoral responses. No significant difference was
      found in anti-HLA antibodies production between the CAD and stable groups.
      CONCLUSIONS: Our data suggest that soluble MICA, at least in a defined range, can
      protect the allograft against natural killers and T cell cytolysis; nonetheless,
      its excessive amounts might stimulate immune system to exert enhanced humoral
      response. In order to confirm the protective or detrimental role of soluble MICA
      in kidney transplantation, conducting larger studies is necessary.

PMID- 25851293
TI  - Association of programmed cell death 1 and programmed cell death 1 ligand gene
      polymorphisms with delayed graft function and acute rejection in kidney allograft
      recipients.
AB  - INTRODUCTION: The genetic variations of co-stimulatory molecules can affect the
      extent of T cell activity during T-cell mediated immunity, especially in
      transplant patients. This study aimed to investigate the association of
      programmed cell death 1 (PDCD1) and programmed cell death 1 ligand 1 (PDCD1LG1)
      gene polymorphisms with clinical outcome of kidney transplantation. MATERIALS AND
      METHODS: A total of 122 patients with a kidney transplant were included in this
      retrospective study. Patients were classified into two groups of biopsy-proven
      acute allograft rejection (AAR) and stable graft function (SGF) during the 5-year
      follow-up period. Four single nucleotide polymorphisms in PDCD1 and PDCD1LG1 were
      determined in the groups of patients as well as in 208 healthy control
      individuals. RESULTS: The frequencies of PD-1.3 (+7146 G>A), PD-1.9 (+7625 C>T),
      PD-L1 (8923 A>C), and PD-L1 (+6777 C>G) genotypes and alleles were not
      significantly different between the AAR and SGF groups. In comparison with
      healthy controls, PD-1.9 (+7625 C>T) genotype and T allele were significantly
      more frequent in all of the patients and in those with SGF. Overall, 27 of 122
      kidney allograft recipients experienced delayed graft function, and a higher
      frequency of PD-1.9 (+7625 C>T) genotype and T allele was observed in this group
      versus those without delayed graft function. Similarly, a significant high
      frequency of this genotype was found among the AAR subgroup of patients with
      delayed graft function. CONCLUSIONS: Our results indicate that potentially
      functional genetic variation in PDCD1 can influence the outcome of kidney
      transplantation.

PMID- 25851295
TI  - Angiosarcoma at dialysis fistula site in a patient on continuous ambulatory
      peritoneal dialysis.
AB  - Arteriovenous fistula (AVF) is the best permanent access for hemodialysis.
      Swelling and pain due to thrombosis and infection is common at fistula site.
      Angiosarcoma is one of rare but important differential diagnosis of these signs.
      We present a patient on CAPD with angiosarcoma at AVF. 

PMID- 25851296
TI  - Recurrent idiopathic membranous glomerulonephritis after kidney transplantation
      and successful treatment with rituximab.
AB  - After renal transplantation approximately forty percent of patients with
      membranous glomerolunephritis (MGN) had a recurrence, most commonly during the
      first year.We present two cases with recurrent MGN after kidney transplantation
      who successfully treated with ritoximab.

PMID- 25851297
TI  - Re: Sex differences in protective effect of recombinant human erythropoietin
      against cisplatin-induced nephrotoxicity in rats.

PMID- 25851299
TI  - New law on consent will overload seriously ill patients.

PMID- 25851298
TI  - A randomised dose-ranging study of tiotropium Respimat(r) in children with
      symptomatic asthma despite inhaled corticosteroids.
AB  - BACKGROUND: A considerable number of children with asthma remain symptomatic
      despite treatment with inhaled corticosteroids, resulting in significant
      morbidity, reduced quality of life, increased healthcare costs and lost school
      days. The aim of our study was to assess the efficacy, safety and tolerability of
      once-daily tiotropium Respimat(r) 5 MUg, 2.5 MUg and 1.25 MUg add-on to medium
      dose inhaled corticosteroids, with or without a leukotriene modifier, in children
      aged 6-11 years with symptomatic asthma. METHODS: In this Phase II, double-blind,
      placebo-controlled, incomplete-crossover, dose-ranging study, patients were
      randomised to receive three of the four treatments evaluated: once-daily
      tiotropium Respimat(r) 5 MUg, 2.5 MUg or 1.25 MUg or placebo Respimat(r), in the
      evening during the 12-week (three * 4-week) treatment period. RESULTS: In total,
      76, 74, 75 and 76 patients aged 6-11 years received tiotropium Respimat(r) 5 MUg,
      2.5 MUg, 1.25 MUg and placebo Respimat(r), respectively. For the primary end
      point (peak forced expiratory volume in 1 second measured within 3 hours post
      dosing), the adjusted mean responses with tiotropium Respimat(r) 5 MUg (272 mL),
      2.5 MUg (290 mL) and 1.25 MUg (261 mL) were significantly greater than with
      placebo Respimat(r) (185 mL; p = 0.0002, p < 0.0001 and p = 0.0011,
      respectively). The safety and tolerability of all doses of tiotropium Respimat(r)
      were comparable with those of placebo Respimat(r), with no serious adverse events
      and no events leading to discontinuation. CONCLUSIONS: Tiotropium Respimat(r) add
      on to medium-dose inhaled corticosteroids, with or without a leukotriene
      modifier, was efficacious in paediatric patients with symptomatic asthma and had
      comparable safety and tolerability with placebo Respimat(r). TRIAL REGISTRATION:
      ClinicalTrials.gov identifier NCT01383499.

PMID- 25851300
TI  - Ultrasound shear wave speed measurements correlate with liver fibrosis in
      children.
AB  - BACKGROUND: Little published research has shown the relationship between
      noninvasive US shear wave speed (SWS) measurements and degree of liver fibrosis
      as established by percutaneous biopsy in children. OBJECTIVE: To assess the
      relationship between liver US shear wave speed (SWS) measurements and parenchymal
      fibrosis in children. MATERIALS AND METHODS: Sixty-two children (0-18 years old)
      with known or suspected liver disease underwent same-day US shear wave
      elastography (SWE) and clinically ordered percutaneous core needle biopsy. SWE
      was performed just before the liver biopsy in the area targeted for sampling,
      using an Acuson S3000 US system with a 9L4 transducer; six SWS measurements were
      acquired using Virtual Touch Quantification (VTQ) and Virtual Touch IQ (VTIQ)
      modes. Biopsy specimens were scored for histological fibrosis and inflammation.
      Bivariate relationships were assessed using Pearson correlation, while multiple
      linear regression analysis was used to establish the relationship between SWS and
      predictor variables. Receiver operating characteristic (ROC) curves were created
      to assess the abilities of VTQ and VTIQ to discern low vs. high liver fibrosis
      (histological fibrosis scores 0-2 vs. 3-6). RESULTS: There were significant
      positive correlations between liver histological fibrosis score and VTQ (n = 49)
      and VTIQ (n = 48) mean shear wave speed measurements (r = 0.68 and r = 0.73; P
      values <0.0001). There also were significant positive correlations between liver
      histological inflammation score and VTQ and VTIQ mean shear wave speed
      measurements (r = 0.47 and r = 0.44, and P = 0.0006 and P = 0.0016,
      respectively). For VTQ, both histological fibrosis (P < 0.0001) and inflammation
      (P = 0.04) scores were significant predictors of shear wave speed (model adjusted
      R (2) = 0.49). For VTIQ, only histological fibrosis score (P < 0.0001) was a
      significant predictor of shear wave speed (model adjusted R (2) = 0.56). ROC
      areas under the curve were 0.84 and 0.86 for VTQ and VTIQ, respectively.
      CONCLUSION: Liver US shear wave speed measurements increase with increasing
      parenchymal fibrosis in children.

PMID- 25851301
TI  - Diagnosis of invasive aspergillosis: recent developments and ongoing challenges.
AB  - BACKGROUND: Invasive aspergillosis is an infection with high morbidity and
      mortality that affects mostly immunocompromised individuals. Early identification
      and targeted treatment of the infection is essential to improve survival of
      affected patients. The purpose of our review is to highlight the most recent
      developments in diagnosis and screening for invasive aspergillosis (IA) along
      with the challenges associated with the development and validation of novel
      diagnostic approaches. METHODS: Ovid MEDLINE and The Cochrane library were
      searched for studies that evaluated serologic, molecular and novel methodologies
      for the diagnosis of IA. RESULTS: Traditional diagnostic approaches, such as
      histopathology and culture, are still considered the gold standard but lack
      sufficient sensitivity. Newer serologic techniques, such as galactomannan (GM)
      and beta-glucan, have already been incorporated into clinical guidelines, but
      recent evidence suggests that their performance might be limited in certain
      clinical settings. Molecular methods, such as the Aspergillus spp. polymerase
      chain reaction (PCR), have not yet found their place in clinical practice mainly
      due to lack of standardization. Novel methodologies, such as volatile organic
      compound detection and lateral flow devices, have recently been developed and
      promise noninvasive and rapid diagnosis of aspergillosis, while diagnostic
      algorithms that incorporate both GM and PCR have proven to be effective in early
      randomized trials as screening methods and can reduce the use of antifungal
      agents. CONCLUSIONS: Diagnosis of IA remains challenging. Novel methodologies and
      the standardization of GM and PCR might provide more reliable diagnostic tools in
      the future.

PMID- 25851302
TI  - Midwifery students receiving the newborn at birth: A pilot study of the impact of
      structured training in neonatal resuscitation.
AB  - The experience of midwifery students in receiving the newborn at birth, before
      and after structured training in neonatal resuscitation: A pilot study. The
      practice of receiving the newborn, including neonatal resuscitation is an
      essential component of midwifery. Anecdotal evidence suggests preparation for the
      task is ad hoc within midwifery curricula, leading to student's anxiety. This
      paper reports impacts of neonatal resuscitation training upon levels of
      knowledge, preparedness, and anxiety for midwifery students receiving the
      newborn. Midwifery students participated in an online questionnaire before and
      after neonatal resuscitation training. The responses collected were subjected to
      descriptive analysis. Of 10 students invited, 6 completed the pre and post course
      questionnaires. Knowledge of the responsibility in receiving the newborn and
      instigation of resuscitation increased after attending the course. Steps to
      prepare to receive the newborn and clinical signs for initial assessment remained
      static. Students felt more prepared to receive the newborn after the course but
      did not improve in their preparation to initiate resuscitation. Anxiety levels
      remained static. Structured neonatal resuscitation training and strategies to
      ensure application of skills learnt should be embedded into midwifery curricula.
      Midwifery students' experience in receiving the newborn and neonatal
      resuscitation is worthy of further study. 

PMID- 25851303
TI  - The Present and the Future of Cost-Related Non-Adherence in Medicare Part D.

PMID- 25851304
TI  - The Use of Technology to Enhance Health.

PMID- 25851305
TI  - In the Office and In-Between: The Role of Panel Management in Primary Care.

PMID- 25851306
TI  - Inherited and environmental influences on a childhood co-occurring symptom
      phenotype: Evidence from an adoption study.
AB  - Risk factors for the childhood development of co-occurring internalizing and
      externalizing symptoms are not well understood, despite a high prevalence and
      poor clinical outcomes associated with this co-occurring phenotype. We examined
      inherited and environmental risk factors for co-occurring symptoms in a sample of
      children adopted at birth and their birth mothers and adoptive mothers (N = 293).
      Inherited risk factors (i.e., birth mothers' processing speed and internalizing
      symptoms) and environmental risk factors (i.e., adoptive mothers' processing
      speed, internalizing symptoms, and uninvolved parenting) were examined as
      predictors for the development of internalizing-only, externalizing-only, or co
      occurring symptoms using structural equation modeling. Results suggested a unique
      pattern of predictive factors for the co-occurring phenotype, with risk conferred
      by adoptive mothers' uninvolved parenting, birth mothers' slower processing
      speed, and the birth mothers' slower processing speed in tandem with adoptive
      mothers' higher internalizing symptoms. Additional analyses indicated that when
      co-occurring-symptom children were incorporated into internalizing and
      externalizing symptom groups, differential risk factors for externalizing and
      internalizing symptoms emerged. The findings suggest that spurious results may be
      found when children with co-occurring symptoms are not examined as a unique
      phenotypic group. 

PMID- 25851308
TI  - Prospective study of the impact of the Prosigna assay on adjuvant clinical
      decision-making in unselected patients with estrogen receptor positive, human
      epidermal growth factor receptor negative, node negative early-stage breast
      cancer.
AB  - PURPOSE: Improved understanding of risk of recurrence (ROR) is needed to reduce
      cases of recurrence and more effectively treat breast cancer patients. The
      purpose of this study was to examine how a gene-expression profile (GEP),
      identified by Prosigna, influences physician adjuvant treatment selection for
      early breast cancer (EBC) and the effects of this influence on optimizing
      adjuvant treatment recommendations in clinical practice. METHODS: A prospective,
      observational, multicenter study was carried out in 15 hospitals across Spain.
      Participating medical oncologists completed pre-assessment, post-assessment, and
      follow-up questionnaires recording their treatment recommendations and confidence
      in these recommendations, before and after knowing the patient's ROR. Patients
      completed questionnaires on decision-making, anxiety, and health status. RESULTS:
      Between June 2013 and January 2014, 217 patients enrolled and a final 200 were
      included in the study. Patients were postmenopausal, estrogen receptor positive,
      human epidermal growth hormone factor negative, and node negative with either
      stage 1 or stage 2 tumors. After receiving the GEP results, treatment
      recommendations were changed for 40 patients (20%). The confidence of medical
      oncologists in their treatment recommendations increased in 41.6% and decreased
      in 6.5% of total cases. Patients reported lower anxiety after physicians made
      treatment recommendations based on the GEP results (p < 0.05). CONCLUSIONS:
      Though this study does not include evaluation of the impact of GEP on long-term
      outcomes, it was found that GEP results influenced the treatment decisions of
      medical oncologists and their confidence in adjuvant therapy selection. Patients'
      anxiety about the selected adjuvant therapy decreased with use of the GEP.

PMID- 25851307
TI  - Extending the amygdala in theories of threat processing.
AB  - The central extended amygdala is an evolutionarily conserved set of
      interconnected brain regions that play an important role in threat processing to
      promote survival. Two core components of the central extended amygdala, the
      central nucleus of the amygdala (Ce) and the lateral bed nucleus of the stria
      terminalis (BST) are highly similar regions that serve complimentary roles by
      integrating fear- and anxiety-relevant information. Survival depends on the
      ability of the central extended amygdala to rapidly integrate and respond to
      threats that vary in their immediacy, proximity, and characteristics. Future
      studies will benefit from understanding alterations in central extended amygdala
      function in relation to stress-related psychopathology. 

PMID- 25851310
TI  - Comparison between the ASSET EZ4 NCO and Impinger Sampling Devices for Aerosol
      Sampling of 4,4'-Methylene Diphenyl Diisocyanate in Spray Foam Application.
AB  - 4,4'-methylene diphenyl diisocyanate (MDI) aerosol exposure evaluation in spray
      foam insulation application is known to be a challenge. Current available
      techniques are either not user-friendly or are inaccurate or are not validated
      for this application. A new sampler has recently been developed to address the
      user-friendliness issues with other samplers: the ASSET EZ4-NCO, but the use of
      this sampler in spray foam insulation applications has not been demonstrated or
      validated. Because of this, the current work was undertaken to provide a
      comparison of the ASSET sampler with an impinger method, considered to be the
      best available method in the context of spray foam insulation, and hence the
      pertinence of comparing this sampler to an impinger method, considered to be the
      best available method for measuring MDI monomer and oligomers for this particular
      application. Liquid chromatography coupled with tandem mass spectrometry method
      for MDI monomer and oligomer analysis was implemented based on the Supelco
      literature. It allows the analysis of MDI-dibutylamine (DBA) and MDI 3-ring-DBA
      with a minimum reported value of 5ng ml(-1), a dynamic range of 5-140ng ml(-1),
      precision <15% and accuracy >80%. This method was used to quantify MDI aerosols
      collected with the ASSET sampler in an MDI spray foam environment in parallel
      with the toluene/MOPIP impinger reference method. The ASSET sampler significantly
      underestimated the levels of MDI monomer and oligomers when compared to the
      reference method. The estimated bias was 72% (95% confidence interval [CI] 54
      89%) for the monomer and 96% (95% CI 76-115%) for the oligomers. These results
      demonstrate the importance of evaluating each new sampler for each isocyanate
      application prior to a formal worker exposure evaluation. 

PMID- 25851309
TI  - Carbon Nanotube and Nanofiber Exposure Assessments: An Analysis of 14 Site
      Visits.
AB  - Recent evidence has suggested the potential for wide-ranging health effects that
      could result from exposure to carbon nanotubes (CNT) and carbon nanofibers (CNF).
      In response, the National Institute for Occupational Safety and Health (NIOSH)
      set a recommended exposure limit (REL) for CNT and CNF: 1 ug m(-3) as an 8-h time
      weighted average (TWA) of elemental carbon (EC) for the respirable size fraction.
      The purpose of this study was to conduct an industrywide exposure assessment
      among US CNT and CNF manufacturers and users. Fourteen total sites were visited
      to assess exposures to CNT (13 sites) and CNF (1 site). Personal breathing zone
      (PBZ) and area samples were collected for both the inhalable and respirable mass
      concentration of EC, using NIOSH Method 5040. Inhalable PBZ samples were
      collected at nine sites while at the remaining five sites both respirable and
      inhalable PBZ samples were collected side-by-side. Transmission electron
      microscopy (TEM) PBZ and area samples were also collected at the inhalable size
      fraction and analyzed to quantify and size CNT and CNF agglomerate and fibrous
      exposures. Respirable EC PBZ concentrations ranged from 0.02 to 2.94 ug m(-3)
      with a geometric mean (GM) of 0.34 ug m(-3) and an 8-h TWA of 0.16 ug m(-3). PBZ
      samples at the inhalable size fraction for EC ranged from 0.01 to 79.57 ug m(-3)
      with a GM of 1.21 ug m(-3). PBZ samples analyzed by TEM showed concentrations
      ranging from 0.0001 to 1.613 CNT or CNF-structures per cm(3) with a GM of 0.008
      and an 8-h TWA concentration of 0.003. The most common CNT structure sizes were
      found to be larger agglomerates in the 2-5 um range as well as agglomerates >5
      um. A statistically significant correlation was observed between the inhalable
      samples for the mass of EC and structure counts by TEM (Spearman rho = 0.39, P <
      0.0001). Overall, EC PBZ and area TWA samples were below the NIOSH REL (96% were
      <1 MUg m(-3) at the respirable size fraction), while 30% of the inhalable PBZ EC
      samples were found to be >1 MUg m(-3). Until more information is known about
      health effects associated with larger agglomerates, it seems prudent to assess
      worker exposure to airborne CNT and CNF materials by monitoring EC at both the
      respirable and inhalable size fractions. Concurrent TEM samples should be
      collected to confirm the presence of CNT and CNF.

PMID- 25851311
TI  - Hypericum perforatum Reduces Paracetamol-Induced Hepatotoxicity and Lethality in
      Mice by Modulating Inflammation and Oxidative Stress.
AB  - Hypericum perforatum is a medicinal plant with anti-inflammatory and antioxidant
      properties, which is commercially available for therapeutic use in Brazil. Herein
      the effect of H. perforatum extract on paracetamol (acetaminophen)-induced
      hepatotoxicity, lethality, inflammation, and oxidative stress in male swiss mice
      were investigated. HPLC analysis demonstrated the presence of rutin, quercetin,
      hypericin, pseudohypericin, and hyperforin in H. perforatum extract. Paracetamol
      (0.15-3.0 g/kg, p.o.) induced dose-dependent mortality. The sub-maximal lethal
      dose of paracetamol (1.5 g/kg, p.o.) was chosen for the experiments in the study.
      H. perforatum (30-300 mg/kg, i.p.) dose-dependently reduced paracetamol-induced
      lethality. Paracetamol-induced increase in plasma aspartate aminotransferase
      (AST) and alanine aminotransferase (ALT) concentrations, and hepatic
      myeloperoxidase activity, IL-1beta, TNF-alpha, and IFN-gamma concentrations as
      well as decreased reduced glutathione (GSH) concentrations and capacity to reduce
      2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonate radical cation; ABTS(+) ) were
      inhibited by H. perforatum (300 mg/kg, i.p.) treatment. Therefore, H. perforatum
      protects mice against paracetamol-induced lethality and liver damage. This effect
      seems to be related to the reduction of paracetamol-induced cytokine production,
      neutrophil recruitment, and oxidative stress.

PMID- 25851312
TI  - Simplified Citrate Anticoagulation for CRRT Without Calcium Replacement.
AB  - Since 2012, citrate anticoagulation is the recommended anticoagulation strategy
      for continuous renal replacement therapy (CRRT). The main drawback using citrate
      as anticoagulant compared with heparin is the need for calcium replacement and
      the rigorous control of calcium levels. This study investigated the possibility
      to achieve anticoagulation while eliminating the need for calcium replacement.
      This was successfully achieved by including citrate and calcium in all CRRT
      solutions. Thereby the total calcium concentration was kept constant throughout
      the extracorporeal circuit, whereas the ionized calcium was kept at low levels
      enough to avoid clotting. Being a completely new concept, only five patients with
      acute renal failure were included in a short, prospective, intensely supervised
      nonrandomized pilot study. Systemic electrolyte levels and acid-base parameters
      were stable and remained within physiologic levels. Ionized calcium levels
      declined slightly initially but stabilized at 1.1 mmol/L. Plasma citrate
      concentrations stabilized at approximately 0.6 mmol/L. All postfilter ionized
      calcium levels were <0.5 mmol/L, that is, an anticoagulation effect was reached.
      All filter pressures were normal indicating no clotting problems, and no visible
      clotting was observed. No calcium replacement was needed. This pilot study
      suggests that it is possible to perform regional citrate anticoagulation without
      the need for separate calcium infusion during CRRT. 

PMID- 25851313
TI  - Influence of Sterilization and Storage Period on Elution of Polyvinylpyrrolidone
      from Wet-Type Polysulfone Membrane Dialyzers.
AB  - The objectives of this study were to investigate the influence of the
      sterilization and storage period on elution of polyvinylpyrrolidone (PVP) from
      wet-type polysulfone (PSu) membrane dialyzers. APS-15SA (APS) dialyzers
      sterilized by gamma-radiation and RENAK PS-1.6 (RENAK) dialyzers sterilized by
      autoclaving were compared in this study. Each dialyzer was washed with
      physiological saline and the amount of PVP eluted from the PSu membrane was
      measured. Then, experimental use of each dialyzer was performed by circulating
      physiological saline for 4 hours, after which the PVP eluted from the PSu
      membrane was measured. As the results, the amount of PVP eluted by washing was
      positively correlated with the storage period for both dialyzers (APS: rs =
      0.958; RENAK: rs = 0.952). In the experimental circuit, the amount of PVP eluted
      from the RENAK dialyzer was positively correlated with the storage period (rs =
      0.810), whereas the amount of PVP eluted from the APS dialyzer was negatively
      correlated with the storage period (rs = -0.833). We found that the amount of PVP
      eluted from PSu membrane is quite different by the sterilization and storage
      period of dialyzers. 

PMID- 25851314
TI  - Development of a Double-Lumen Cannula for a Percutaneous RVAD.
AB  - The objectives were to design/fabricate a double-lumen cannula (DLC) for a
      percutaneous right ventricular assist device (pRVAD) and to test the
      feasibility/performance of this pRVAD system. A 27 Fr DLC prototype was made and
      tested in six adult sheep. The pRVAD DLC was inserted into the right jugular
      vein; advanced through the superior vena cava, the right atrium (RA), the right
      ventricle (RV); ending in the pulmonary artery (PA). A CentriMag pump and
      optional gas exchanger were connected to the DLC. Blood was withdrawn from RA,
      pumped through gas exchanger, and perfused PA. Maximal pumping flow was
      maintained for 2 hours. The pRVAD DLC was successfully deployed in all six sheep.
      In first three sheep, maximal average pumping flow was less than 3 L/min because
      the DLC was advanced too far with drainage opening against RA side wall. In last
      three sheep with well-positioned DLC, average maximal flow was more than 3.5
      L/min. The gas exchanger provided up to 230 ml/min CO2 removal and 174 ml/min O2
      transfer. Our DLC-based pRVAD system is feasible for percutaneous right heart and
      respiratory assistance through a single cannulation. The pRVAD DLC can be easily
      placed prophylactically during left ventricular assist device implantation and
      removed as needed without additional open chest procedures.

PMID- 25851315
TI  - Successful Porcine Renal Transplantation After 60 Minutes of Donor Warm Ischemia:
      Extracorporeal Perfusion and Thrombolytics.
AB  - Donation from uncontrolled circulatory determination of death donors (uDCD) is
      impractical in United States because of the time needed to organize procurement
      before irreversible organ damage. Salvaging organs after prolonged warm ischemic
      time (WIT) may address this limitation. We evaluated the combination of
      extracorporeal support (ECS) and thrombolytics in a porcine uDCD renal transplant
      model. Nonanticoagulated uDCD sustained 60 min of WIT, and two groups were
      studied. Rapid recovery (RR)-uDCD renal grafts procured using the standard quick
      topical cooling and renal flush, and ECS-assisted donation (E-uDCD), 4 hr ECS
      plus thrombolytics for in situ perfusion before procurement. All kidneys were
      flushed and cold stored, followed by transplantation into healthy nephrectomized
      recipients without immunosuppression. Delayed graft function (DGF) was defined as
      creatinine more than 5.0 mg/dl on any postoperative day. Twelve kidneys in E-uDCD
      and 6 in RR-uDCD group were transplanted. All 12 E-uDCD recipients had urine
      production and adequate function in the first 48 hr, but two grafts (16.7%) had
      DGF at 96 hr. All six recipients from RR-uDCD group had DGF at 48 hr and were
      killed. Creatinine and blood urea nitrogen (BUN) levels were significantly lower
      in E-uDCD compared with RR-uDCD group at 24 hr (2.9 +/- 0.7 mg/dl vs. 5.2 +/- 0.9
      mg/dl) and 48 hr (3.2 +/- 0.9 mg/dl vs. 7.2 +/- 1.0 mg/dl); BUN levels at 24 and
      48 hr were 28.3 +/- 6.7 mg/dl vs. 39.5 +/- 7.5 mg/dl and 23.9 +/- 5.0 mg/dl vs.
      46 +/- 12.9 mg/dl, respectively. Thrombolytics plus ECS precondition organs in
      situ yielding functional kidneys in a porcine model of uDCD with 60 min of WIT.
      This procurement method addresses logistical limitations for uDCD use in the
      United States and could have a major impact on the organ donor pool.

PMID- 25851316
TI  - The image of submitral aneurysm with multiple fistulas.

PMID- 25851317
TI  - Antenatal diagnosis of idiopathic arterial calcification with hydrops fetalis.

PMID- 25851318
TI  - Cardiac CT angiography for device surveillance after endovascular left atrial
      appendage closure.
AB  - AIMS: Left atrial appendage (LAA) device imaging after endovascular closure is
      important to assess for device thrombus, residual leak, positioning, surrounding
      structures, and pericardial effusion. Cardiac CT angiography (CCTA) is well
      suited to assess these non-invasively. METHODS AND RESULTS: We report our
      consecutive series of non-valvular atrial fibrillation patients who underwent
      CCTA post-LAA closure with Amplatzer Cardiac Plug (ACP), Amulet (second
      generation ACP), or WATCHMAN devices. Patients underwent CCTA typically 1-6
      months post-implantation. Prospective cardiac-gated CCTA was performed with
      Toshiba 320-detector or Siemens 2nd generation 128-slice dual-source scanners,
      and images interpreted with VitreaWorkstationTM. GFR <30 mL/min/1.73 m(2) was an
      exclusion. We assessed for device thrombus, residual LAA leak, device
      embolization, position, pericardial effusion, optimal implantation, and device
      lobe dimensions. Forty-five patients underwent CCTA at median 97 days post-LAA
      closure (18 ACP, 9 Amulet, 18 WATCHMAN). Average age was 75.5 +/- 8.9 years, mean
      CHADS2 score 3.1 +/- 1.3, and CHADS-VASc score 4.9 +/- 1.6. All had
      contraindications to oral anticoagulation. Post-procedure, 41 (91.1%) were
      discharged on DAPT. There was one device embolization (ACP, successfully
      retrieved percutaneously) and one thrombus (WATCHMAN, resolved with 3 months of
      warfarin). There were two pericardial effusions, both pre-existing and not
      requiring intervention. Residual leak (patency) was seen in 28/44 (63.6%), and
      the mechanisms of leak were readily identified by CCTA (off-axis device, gaps at
      orifice, or fabric leak). Mean follow-up was 1.2 +/- 1.1year, with no death,
      stroke, or systemic embolism. CONCLUSION: CCTA appears to be a feasible
      alternative to transoesophageal echocardiography for post-LAA device surveillance
      to evaluate for device thrombus, residual leak, embolization, position, and
      pericardial effusion.

PMID- 25851319
TI  - Temporal changes in the use and results of exercise echocardiography.
AB  - AIMS: Limited data are available regarding changes over time in referral patterns
      and outcomes of non-invasive cardiac stress testing. Our aim was to evaluate the
      temporal changes in the use and results of exercise echocardiography in our area
      of reference. METHODS AND RESULTS: A total of 12 339 patients referred to our
      unit for exercise echocardiography between 1997 and 2012 were included. We
      divided the 16-year period into four quadrennia and evaluated the changes in
      clinical data, results of the tests, referrals for invasive management and
      outcomes. We observed a gradual decrease in the frequency of detection of
      myocardial ischaemia from 35.3% in1997-2000 to 25.4% in 2009-12 (P < 0.001).
      There was also a progressive increase in the prevalence of cardiovascular risk
      factors and in the frequency of non-ischaemic chest pain and dyspnoea, while the
      proportion of patients with prior myocardial infarction and non-interpretable
      electrocardiograms declined. The rate of referral to coronary angiography within
      6 months decreased from 24.8% in 1997-2000 to 19.6% in 2009-12 (P < 0.001), but
      the rate of coronary revascularization remained almost unchanged (13.1 to 11.7%,
      P for the trend = 0.16). We also observed a progressive decrease in the 1-year
      mortality rate from 3.4 to 1% (P < 0.001). CONCLUSION: Over a 16-year period,
      there was a gradual decrease in the frequency of myocardial ischaemia among
      patients referred to our unit for exercise echocardiography, which was parallel
      to changes in their clinical profile. However, this was not accompanied by a
      significant reduction in the rate of coronary revascularization.

PMID- 25851320
TI  - Prosthetic valve endocarditis: multiple complications in one patient.

PMID- 25851321
TI  - Aortic forward flow in aortic atresia via ventriculo-coronary arterial
      connections.

PMID- 25851322
TI  - Atrioesophageal fistula and pneumocephalus after pulmonary vein isolation.

PMID- 25851323
TI  - Factors associated with B-lines after exposure to hypobaric hypoxia.
AB  - AIMS: Increased extravascular lung water (EVLW) is seen as B-lines on chest
      ultrasonography. In lowlanders ascending to altitude the time course,
      relationship with the patient's clinical status and factors affecting B-lines are
      still unclear. The aim was to monitor B-lines, clinical status and N-terminal B
      type natriuretic peptide (NT-proBNP) during exposure to high altitude. METHODS
      AND RESULTS: Chest ultrasonography, blood samples, cardiovascular parameters, and
      signs and symptoms of high altitude pulmonary oedema (HAPE) were prospectively
      assessed in 19 participants at baseline and after ascent to 3830 m (9, 24, 48, 72
      h, and 8 days) by blinded investigators. Potential confounding factors (e.g.
      altitude variations, physical effort) were minimized. Generalized estimating
      equations were used to analyse factors associated with B-lines. B-lines changed
      with exposure to altitude (P = 0.006) in a parabolic-like pattern within the
      first 72 h; 10 of 18 participants (55.6%) had >5 B-lines at 24 h. B-lines were
      correlated with the number of signs and symptoms (partial coefficient = 0.372, P
      = 0.001). B-lines were associated with time (P = 0.038), sex (P = 0.013), and
      SpO2 (P = 0.042), but not with NT-proBNP (P = 0.546). The participant with a
      clinical diagnosis of HAPE had 23 B-lines. CONCLUSION: B-lines during exposure to
      altitude seem to reflect the individual response to hypobaric hypoxia and
      represent clinically relevant alterations at high altitude, also in patients with
      HAPE. Similar to previous studies, our results support a non-cardiogenic
      aetiology of B-lines.

PMID- 25851324
TI  - Basal hyperaemia is the primary abnormality of perfusion in Takotsubo
      cardiomyopathy: a quantitative cardiac perfusion positron emission tomography
      study.
AB  - AIMS: Takotsubo cardiomyopathy (TTC) is characterized by acute completely
      reversible regional left ventricle (LV) akinesia and decreased tracer uptake in
      the akinetic region on semi-quantitative perfusion imaging. The latter may be due
      to normoperfusion of the akinetic mid/apical area and basal hyperperfusion. Our
      aim was to examine abnormalities of perfusion in TTC, and we hypothesized that
      basal hyperperfusion is the primary perfusion abnormality in the acute state.
      METHOD AND RESULTS: Twenty-five patients were diagnosed with TTC due to (i) acute
      onset of symptoms, (ii) typical apical ballooning, (iii) absence of significant
      coronary disease, and (iv) complete remission on 4-month follow-up. The patients
      underwent coronary angiography (CAG), echocardiography, cardiac magnetic
      resonance imaging (CMR), and (13)NH3/(82)Rb positron emission tomography (PET) in
      the acute state and-except CAG-on follow-up. Patients initially had severe heart
      failure, mid/apical oedema but no infarction, and a rise in cardiac biomarkers.
      On initial perfusion PET imaging, eight patients appeared to have normal, whereas
      17 patients had impaired LV perfusion. In the latter, flow in the basal region
      was increased in the acute state (1.5 +/- 0.1 vs. 1.2 +/- 0.1 mL/g/minRPP
      corrected, P < 0.01), whereas midventricular (1.7 +/- 0.1 vs. 1.6 +/- 0.1
      mL/g/minRPP-corrected, P = 0.21) and apical (1.4 +/- 0.1 vs. 1.5 +/- 0.1
      mL/g/minRPP-corrected, P = 0.36) flow was unchanged between acute and follow-up,
      and within normal range. CONCLUSION: Our results suggest an abnormal LV perfusion
      distribution in the acute state of TTC with basal hyperperfusion and a
      normoperfused akinetic region. The proportion of patients without visualized
      perfusion abnormalities in the acute state may represent a subgroup with fast
      remission.

PMID- 25851326
TI  - Cardiovascular magnetic resonance of a hiatus hernia causing positional cardiac
      compression.

PMID- 25851325
TI  - Right ventricular echocardiographic indices predict poor outcomes in infants with
      persistent pulmonary hypertension of the newborn.
AB  - AIMS: Infants with persistent pulmonary hypertension of the newborn (PPHN) have
      elevated pulmonary vascular resistance that can lead to right ventricular (RV)
      failure and death. Clinicians must decide which infants will fail conventional
      therapy and require transfer to extra corporeal membrane oxygenation (ECMO)
      centres, but accurate echocardiographic predictors have not been identified. We
      assessed echocardiographic measurements of RV pressure and function in predicting
      progression to death or ECMO in infants with PPHN. METHODS AND RESULTS:
      Echocardiograms for infants >=35-week gestation with a clinical diagnosis of PPHN
      were retrospectively reviewed. Traditional and strain echocardiographic measures
      were compared for those with or without the primary outcome of
      ECMO/cardiovascular death. Receiver operator curves identified cut points for
      measures that were significantly different. Of the 86 subjects analysed, 25 (29%)
      of the patients had the primary outcome of ECMO/death. The ECMO/death group had
      diminished tricuspid annular plane systolic excursion (TAPSE; P = 0.002) and RV
      global longitudinal peak strain (GLPS; P = 0.03), a predominant right-to-left
      shunt across the patent ductus arteriosus (PDA; P = 0.05), and an elevated
      oxygenation index (OI; P < 0.001). Sensitivity/specificity for TAPSE <4 mm was 56
      and 85%, and for GLPS greater than or equal to -9% was 52 and 77%. CONCLUSION:
      TAPSE, GLPS, and right-to-left PDA shunting were associated with progression to
      death/ECMO. RV free wall strain was not associated with the outcome, suggesting
      that diminished global strain better reflects clinical outcomes in this group.
      These thresholds may assist in the decision-making to transfer high-risk infants
      to ECMO centres.

PMID- 25851327
TI  - Simultaneous huge apical left ventricular diverticulum and a narrow annulus over
      the narrow neck.

PMID- 25851328
TI  - Spontaneous arteriovenous fistula of left internal iliac artery aneurysm.

PMID- 25851329
TI  - Non-invasive myocardial work index identifies acute coronary occlusion in
      patients with non-ST-segment elevation-acute coronary syndrome.
AB  - AIMS: Acute coronary artery occlusion (ACO) occurs in ~30% of patients with non
      ST-segment elevation-acute coronary syndrome (NSTE-ACS). We investigated the
      ability of a regional non-invasive myocardial work index (MWI) to identify ACO.
      METHODS AND RESULTS: Segmental strain analysis was performed before coronary
      angiography in 126 patients with NSTE-ACS. Left ventricular (LV) pressure was
      estimated non-invasively using a standard waveform fitted to valvular events and
      scaled to systolic blood pressure. MWI was calculated as the area of the LV
      pressure-strain loop. Empirical cut-off values were set to identify segmental
      systolic dysfunction for MWI (<1700 mmHg %) and strain (more than -14%). The
      number of dysfunctional segments was used in ROC analysis to identify ACO. The
      presence of >=4 adjacent dysfunctional segments assessed by MWI was significantly
      better than both global strain and ejection fraction at detecting the occurrence
      of ACO (P < 0.05). Regional MWI had a higher sensitivity (81 vs. 78%) and
      especially specificity (82 vs. 65%) compared with regional strain. Logistic
      regression demonstrated that elevated systolic blood pressure significantly
      decreased the probability of actual ACO in a patient with an area of impaired
      regional strain. CONCLUSION: The presence of a region of reduced MWI in patients
      with NSTE-ACS identified patients with ACO and was superior to all other
      parameters. The regional MWI was able to account for the influence of systolic
      blood pressure on regional contraction. We therefore propose that MWI may serve
      as an important clinical tool for selecting patients in need of prompt invasive
      treatment.

PMID- 25851330
TI  - Bi-ventricular contractile reserve offers an incremental prognostic value for
      patients with dilated cardiomyopathy.
AB  - AIMS: Right ventricular (RV) as well as left ventricular (LV) function has been
      recognized as an important prognostic factor for heart failure patients. Our
      objective was thus to investigate the prognostic significance of combined
      assessment of bi-ventricular functional reserve for patients with dilated
      cardiomyopathy (DCM). METHODS AND RESULTS: We studied 104 DCM patients with
      ejection fractions (EF) of 32 +/- 9%, and speckle-tracking echocardiography was
      used to assess both RV and LV contractile reserve under dobutamine stress (20
      ug/kg/min). RV contractile function was measured as peak global longitudinal
      strain (GLS) from the RV free wall (RV-free), and LV function as global
      circumferential strain (GCS) and GLS, respectively. Event-free survival was then
      tracked for 17 months. Twenty-one patients (20%) developed cardiovascular events.
      A multivariate Cox proportional-hazards analysis revealed that the baseline EF,
      E/A, and the relative change in EF (DeltaEF), in GCS (DeltaGCS), and in RV-free
      (DeltaRV-free) during dobutamine stress were the independent predictors of
      cardiovascular events (P < 0.001, <0.05, <0.01, <0.05, and <0.01, respectively).
      A Cox model based on baseline clinical and echocardiographic variables (chi(2) =
      23.6) was improved by the addition of LV contractile reserve parameters (plus
      DeltaGCS and DeltaEF) (chi(2) = 49.1; P < 0.001) and further improved by adding
      RV contractile reserve (plus DeltaRV-free) (chi(2) = 60.3, P < 0.001).
      CONCLUSION: Assessment of RV contractile reserve during dobutamine stress offers
      a significantly better prognostic value for patients with DCM. Bi-ventricular
      contractile reserve may be required for a favourable outcome, so that estimation
      of RV contractile reserve should be considered part of a comprehensive functional
      assessment of these patients.

PMID- 25851331
TI  - Influence of case-based e-learning on students' performance in point-of-care
      ultrasound courses: a randomized trial.
AB  - BACKGROUND: Theoretical knowledge, visual perception, and sensorimotor skills are
      key elements in ultrasound education. Classroom-based presentations are used
      routinely to teach theoretical knowledge, whereas visual perception and
      sensorimotor skills typically require hands-on training (HT). We aimed to compare
      the effect of classroom-based lectures versus a case-based e-learning (based on
      clinical cases only) on the hands-on performance of trainees during an emergency
      ultrasound course. PARTICIPANTS AND METHODS: This is a randomized, controlled,
      parallel-group study. Sixty-two medical students were randomized into two groups
      [group 1 (G1) and group 2 (G2)]. G1 (n=29) was subjected to a precourse e
      learning, based on 14 short screencasts (each 5 min), an on-site discussion (60
      min), and a standardized HT session on the day of the course. G2 (n=31) received
      classroom-based presentations on the day of the course before an identical HT
      session. Both groups completed a multiple-choice (MC) pretest (test A), a
      practical postcourse test (objective structured clinical exam), and MC tests
      directly after the HT (test B) and 1 day after the course (test C). The Mann
      Whitney U-test was used for statistical analysis. RESULTS: G1 performed markedly
      better in test A (median 84.2, 25%; 75% percentile: 68.5; 92.2) compared with G2
      (65.8; 53.8; 80.4), who had not participated in case-based e-learning (P=0.0009).
      No differences were found in the objective structured clinical exam, test B, and
      test C. CONCLUSION: e-learning exclusively based on clinical cases is an
      effective method of education in preparation for HT sessions and can reduce
      attendance time in ultrasound courses.

PMID- 25851332
TI  - A retrospective review of sudden onset severe headache and subarachnoid
      haemorrhage on the clinical decision unit: looking for a needle in a haystack?
AB  - INTRODUCTION: Patients commonly present to the Emergency Department with sudden
      onset acute severe headache, but exclusion of significant secondary causes,
      particularly subarachnoid haemorrhage (SAH), is vital. The misdiagnosis of SAH is
      most likely in patients with a normal neurological examination, and the
      consequences can be disastrous. A noncontrast computed tomography (CT) brain scan
      is the initial investigation of choice, and most would recommend that, if
      negative, this be followed by a lumbar puncture (LP) and cerebrospinal fluid
      (CSF) analysis. Many hospitals in the UK have developed Clinical Decision Unit
      (CDU) pathways to provide a standardized approach to the investigation and
      management of neurologically normal patients with headache suggestive of SAH.
      AIMS: The aims of this study were to describe the prevalence of SAH and to
      evaluate the performance of CT and LP in a CDU population with sudden onset acute
      severe headache. METHODS: A retrospective review of neurologically pristine
      patients admitted to a CDU pathway for exclusion of SAH was conducted. Structured
      case notes were reviewed; patient demographics, investigation results and
      clinical outcomes were recorded in each case. RESULTS: The overall prevalence of
      SAH in this population was 14/517 (2.7%). A noncontrast CT of the brain had a
      negative predictive value of 99.8%, reducing the post-test probability of having
      an angiogram-positive SAH detected by LP and CSF analysis to 0.21% (95%
      confidence interval 0.04-0.36%). CONCLUSION: The management of neurologically
      pristine patients with sudden onset severe headache on a CDU pathway is feasible.
      In light of the low prevalence of SAH in this population, the decision to follow
      a negative CT with an LP in all cases needs careful consideration, as CSF results
      may only rarely confer therapeutic benefit to patients suspected of SAH.

PMID- 25851333
TI  - A combination of clinical parameters and blood-gas analysis identifies patients
      at risk of transfer to intensive care upon arrival to the Emergency Department.
AB  - OBJECTIVES: Identifying patients at risk of transfer to the ICU upon arrival to
      the Emergency Department (ED) might direct early therapy and optimize transfers.
      However, among the many ED patients, it is difficult to pinpoint the few who
      insidiously deteriorate to an ICU-requiring level. The aim of this study was to
      identify predictors in background information, vital values and blood-gas
      analysis for transfer to ICU 3-36 h after arrival among nontrauma ED patients.
      METHODS: A case-control study of 10 007 acute adult patients admitted to ED
      within 1 year was carried out. The case group consisted of all ICU transfers 3-36
      h after arrival who underwent blood-gas analysis and a similar control group not
      transferred to the ICU. Blood pressure, respiratory frequency, pulse rate,
      peripheral oxygen saturation and temperature, triage, height, weight, Glasgow
      Coma Score, drugs, alcohol, tobacco, age, sex, Charlson score and blood-gas
      results were analysed. RESULTS: A total of 49 medical and 33 surgical patients
      were transferred to the ICU. For medical cases, 2.3 and surgical cases 3.7
      controls were included. For medical patients, low systolic blood pressure [odds
      ratio (OR) 14.4], elevated heart rate (OR 3.9), severe acidosis (OR 5.1) and
      hypercapnia (OR 8.4) and for surgical patients age 60-79 years (OR 6.3), low
      diastolic blood pressure (OR 2.7) and severe acidosis (OR 15.3) were associated
      significantly with later transfer to the ICU. CONCLUSION: The predictors
      identified could be used as part of ED triage to identify high-risk patients for
      ICU. These findings should be examined in a well-designed prospective cohort
      study.

PMID- 25851334
TI  - Contact sensitisation in patients with chronic leg ulcers.
AB  - The aim of our study is to identify the allergens in patients with leg ulcers who
      have contact dermatitis surrounding the skin of the ulcer and compare them with a
      control group consisting of patients with lower extremity contact dermatitis. A
      total of 40 patients with chronic leg ulcers (CLU) and contact dermatitis around
      the skin of ulcer were included in the study. As a control group, 20 patients
      with contact dermatitis of lower extremity without leg ulcers were included. The
      patient and control groups were patch tested with 37 allergens of the European
      Standard Series. Of the 40 patients, 31 (77.5%) had positivity to one or more
      allergens, and 10 (50%) of the control group patients had positivity to one or
      more allergens. The number of patients who had positivity to at least one
      allergen was significantly higher in the patient group (P < 0.05). Positivity to
      the balsam of Peru and benzocaine was significantly higher in the patient group
      than that in the control group (P < 0.05). Contact sensitisation to benzocaine
      and balsam of Peru was found to be associated with the presence of CLU. The
      efficacy of therapy in patients with leg ulcers might be increased by avoiding
      these allergens.

PMID- 25851335
TI  - Systematizing cultural awareness: Toward a model for modification of trauma
      therapy and an application in Turkey.
AB  - A cross-cultural team including a U.S.-trained clinical cross-cultural
      psychologist and two Turkish psychiatrists conducted research on a set of five
      trauma treatment psychotherapy groups for adult women survivors of sexual abuse
      in Ankara, Turkey. Based upon observational comparisons between trauma treatment
      groups in U.S. and Turkish settings, the team developed an approach to assist in
      adaptation of treatment methods from one cultural setting to another. This is a
      preliminary effort to develop a conceptual tool to focus the attention of
      therapists on salient dimensions of culture that may influence the psychotherapy
      process. This article describes six possible dimensions: (a)
      relational/individual self; (b) situationalism/universalism; (c) high/low power
      differential; (cc) high/low gender differential; (d) internal/external control;
      (e) emotional expressivity/containment; and (f) short-term/long-term time
      orientation. Comparative cultural examples from trauma psychotherapy group field
      notes illustrate the use of the tool.

PMID- 25851336
TI  - Effects of a culturally sensitive assessment on symptom profiles in native Dutch
      and Moroccan patients with a first psychosis referral.
AB  - Previous studies have reported a higher incidence of psychosis in Moroccan
      immigrants in the Netherlands than among native-born residents. However, this
      disparity was substantially attenuated when cultural differences in symptom
      presentation were taken into account. To better understand the impact of
      different diagnostic procedures on incidence rates, we examined the effects of
      the use of a culturally sensitive diagnostic interview, compared to a standard
      semi-structured diagnostic interview, on symptom profiles among Moroccan
      immigrant and native Dutch patients in the Netherlands. A total of 26 Dutch and
      26 Moroccan patients referred with a possible first psychosis diagnosis were
      interviewed twice: once with the standard version and once with a culturally
      adapted version of the Comprehensive Assessment of Symptoms and History
      questionnaire (CASH and CASH-CS, respectively). Among native Dutch patients,
      symptoms profiles based on CASH and CASH-CS interviews were very similar. By
      contrast, among Moroccan immigrant patients, symptom profiles based on CASH and
      CASH-CS interviews differed substantially, with more mania symptoms (+30%; p <
      .05) and fewer delusions (-31%; p < .05) reported when using the CASH-CS. These
      results suggest that the over-diagnosis of schizophrenia in Moroccan immigrants
      with a first psychosis referral may be related to a tendency to under-detect mood
      symptoms and over-detect positive psychotic symptoms when a standard diagnostic
      procedure is used. This bias may be corrected, at least in part, by the use of a
      culturally sensitive interview instrument such as the CASH- CS. 

PMID- 25851338
TI  - Genetic Variations in Glutathione Pathway Genes Predict Cancer Recurrence in
      Patients Treated with Transurethral Resection and Bacillus Calmette-Guerin
      Instillation for Non-muscle Invasive Bladder Cancer.
AB  - BACKGROUND: Glutathione (GSH) is an important molecule involved in cell
      detoxification and antioxidation and may affect cancer development or outcome. We
      hypothesized that genetic variation in the GSH pathway might influence the
      clinical outcome of patients who have non-muscle invasive bladder cancer (NMIBC).
      METHODS: A total of 114 single nucleotide polymorphisms (SNPs) in 21 GSH pathway
      genes were genotyped in 414 NMIBC patients treated with transurethral resection
      alone (TUR) and both TUR and intravesical bacillus Calmette-Guerin instillation
      (BCG) therapy. The effect of each SNP on time to recurrence was estimated using
      the multivariate Cox proportional hazards model. Cumulative effect and survival
      tree analyses were performed to determine the joint effects of unfavorable
      genotypes and gene-gene interactions on bladder cancer prognosis. RESULTS: Seven
      SNPs showed significant associations with cancer recurrence in the TUR group and
      15 SNPs showed significant associations with recurrence in the BCG group. The
      most significant SNP in the TUR group was rs3746162 in GPX4, whose variant
      genotype conferred a 5.4-fold increased risk of recurrence compared with wild
      type (hazard ratio [HR] = 5.43, 95 % confidence interval [CI] = 2.19-13.46),
      whereas the most significant SNP in the BCG group was rs7265992 in GSS (HR 3.43,
      95 % CI 1.56-7.56). The risk of recurrence increased with the number of
      unfavorable genotypes in both groups. Within treatment group, stratified analyses
      by tumor grade also indicated predictive variants. CONCLUSIONS: Genetic variants
      in GSH pathway may influence cancer recurrence in NMIBC patients receiving
      curative treatment.

PMID- 25851339
TI  - Preoperative Chronic Kidney Disease Status is an Independent Prognostic Factor in
      Patients with Renal Cell Carcinoma.
AB  - PURPOSE: Preoperative chronic kidney disease (CKD) status may affect disease
      outcomes in patients with renal cell carcinoma (RCC). This study evaluated the
      influence of preoperative CKD status on clinicopathological features and
      prognosis in patients with RCC. METHODS: Between 1999 and 2011, a total of 1855
      patients underwent radical nephrectomy at various centers throughout Korea. Of
      these patients, 1655 had an estimated glomerular filtration rate (eGFR) >=60
      ml/min/1.73 m(2) (non-CKD group) and 200 patients had an eGFR >=30 but <60
      ml/min/1.73 m(2) (CKD group). To reduce the effects of selection bias and
      potential confounding factors, 600 patients in the non-CKD group were selected by
      propensity-score matching. RESULTS: The median age of all patients was 57.3 years
      (range 20-94 years) and the median follow-up was 35.0 months (range 1-154
      months). Comparisons of the propensity-score-matched cohorts showed that T and N
      stages were more advanced and tumor size was larger in the CKD group than in the
      non-CKD group (p < 0.05 each). Kaplan-Meier analyses showed that recurrence-free
      survival, cancer-specific survival (CSS), and overall survival (OS) were
      significantly lower in the CKD group (p < 0.01 each). Multivariate regression
      analysis showed that preoperative CKD status was an independent predictor of CSS
      and OS in patients with RCC (p < 0.05 each). CONCLUSIONS: Preoperative CKD may be
      associated with more aggressive features and poorer prognosis in patients with
      RCC. RCC patients with preoperative CKD should be carefully and frequently
      followed-up after nephrectomy.

PMID- 25851340
TI  - Erratum to: Outcomes of Modified Harrington Reconstructions for Nonprimary
      Periacetabular Tumors: An Effective and Inexpensive Technique.

PMID- 25851341
TI  - The Effect of Thyroiditis on the Yield of Central Compartment Lymph Nodes in
      Patients with Papillary Thyroid Cancer.
AB  - BACKGROUND: In patients who have undergone thyroidectomy and central compartment
      neck dissection (CCND) for papillary thyroid cancer (PTC), visualization of
      enlarged lymph nodes may lead to more extensive CCND. This study sought to
      determine the effect of patient age and the presence of thyroiditis on the number
      of malignant and total lymph nodes resected in patients who underwent CCND for
      PTC. METHODS: This retrospective review examined a prospective database of
      patients who underwent total thyroidectomy and CCND for PTC between April 2009
      and June 2013 and had thyroiditis on the final pathology. The patients were
      categorized into age groups by decade (18-29, 30-39, 40-49, 50-59, and >=60
      years) and compared with a control group of patients matched by age, gender, and
      tumor size. RESULTS: Of 74 patients with thyroiditis, 64 (87 %) were women. The
      median age of the patients was 47.5 years (range 18.2-72.0 years). The patients
      with thyroiditis had more lymph nodes resected than those without thyroiditis
      (median 11 vs 7; p < 0.01). However, these patients had fewer malignant lymph
      nodes (median 0 vs 1.5; p = 0.06), resulting in a lower lymph node ratio (0 vs
      0.18; p = 0.02) for the entire cohort, but particularly for the youngest (18-29
      years) and oldest (>=60 years) age groups. CONCLUSIONS: Patients with thyroiditis
      and PTC who underwent CCND had more lymph nodes resected but a had lower
      proportion of metastatic lymph nodes than those without thyroiditis. Given the
      relatively low yield of malignant cervical lymphadenopathy, a more judicious
      approach to CCND might be considered, particularly for the youngest and oldest
      patients with PTC and thyroiditis.

PMID- 25851342
TI  - Preferential occupancy of strontium in the hydroxyapatite lattice in biphasic
      mixtures formed from non-stoichiometric calcium apatites.
AB  - The present study reports the variations in phase content of biphasic mixtures
      and structural changes induced by different levels of strontium addition in
      calcium-deficient apatite (Ca/P = 1.60) powders during heat treatment. The
      synthesis was attempted by an in situ aqueous precipitation technique and X-ray
      diffraction, Raman spectroscopy and Rietveld refinement of the powder X-ray
      diffraction data were employed for comprehensive analysis. The results confirm
      the preferential occupancy of Sr(2+) at two different Ca(2+) sites of the
      hydroxyapatite [Ca10(PO4)6(OH)2, HAP] lattice, with the Ca(2+) (2) site
      accommodating more Sr(2+) than the Ca(2+) (1) site. Increasing Sr(2+) addition in
      calcium-deficient apatite has led to a decline in the phase content of beta
      tricalcium phosphate [beta-Ca3(PO4)2, beta-TCP] in biphasic mixtures of HAP and
      beta-TCP. Sr(2+) addition exceeding the critical limit of a (Ca + Sr)/P > 1.75
      molar ratio has resulted in the formation of CaO as an additional phase, and this
      justifies the lack of enough PO4(3-) ions to promote any kind of calcium
      phosphate precipitation. Sr(2+) accommodation in the lattice sites of HAP has
      induced an increase in the lattice parameters and has also led to the significant
      distortion of the PO4 tetrahedron and OH groups, confirmed by Raman and FT-IR
      spectroscopic techniques. 

PMID- 25851343
TI  - Endovascular Treatment of Middle Cerebral Artery Aneurysm with the LVIS Junior
      Stent.
AB  - BACKGROUND: Middle cerebral artery (MCA) aneurysms often occur in small parent
      vessels and are incorporated with the orifice of acute-angled efferent branch
      vessels. Endovascular treatment for these aneurysms remains technically
      challenging. This study aimed to assess the clinical safety and efficacy of the
      Low-profile Visualized Intraluminal Support Junior (LVIS Jr) stent for
      embolization of MCA aneurysms. METHODS: Eighteen intracranial aneurysms,
      including 13 unruptured and 5 ruptured aneurysms, were treated with LVIS Jr stent
      assisted coil embolization. The clinical data and technical results are
      presented. RESULTS: A total of 18 stents were successfully delivered to the
      target aneurysms, and the technical success rate was 100%. There was complete
      occlusion in 8 (44.4%) of 18 cases, neck remnants in 7 (38.9%) cases, and partial
      occlusion in 3 (16.7%) cases. In-stent thrombosis occurred in 1 case, and the
      symptoms disappeared after transvenous tirofiban injection. The modified Rankin
      Scale score at discharge was 0 in 14 patients, 1 in 3 patients, and 2 in 1
      patient. CONCLUSIONS: The LVIS Jr stent provided excellent trackability and
      deliverability and is safe and effective for the treatment of wide-necked MCA
      aneurysms with tortuous and smaller parent vessels.

PMID- 25851344
TI  - Effects of mental practice with action observation training on occupational
      performance after stroke.
AB  - BACKGROUND: Studies on whether mental practice (MP) in patients with stroke using
      action observation training (AOT) is effective in improving physical performance
      are still insufficient. To examine the effects of MP on both occupational
      performance and motor function to complement studies relevant to MP with AOT.
      METHODS: Subjects of this study were 3 individuals who were diagnosed with
      stroke. We used an A-B-A study design with follow-up evaluation, which is a type
      of reversal single experimental research design. A total of 20 experimental
      sessions were conducted. To assess the long-term effect of MP with AOT, follow-up
      baseline measurements were made after 2 weeks without MP. Three-dimensional
      motion analysis and electromyography were conducted during each of the 20
      sessions. The Motor Activity Log and Assessment of Motor and Process Skills were
      measured 3 times: in the pre-MP phase, the post-MP phase, and the 2-week follow
      up phase. RESULTS: Occupational performance improved after intervention in all 3
      subjects when applying an MP task using AOT. All subjects showed improvement of
      motor functions, including smoothness of movement, agonistic muscle activation,
      and co-ordination. The treatment effect continued after 2 weeks. CONCLUSIONS: MP
      using AOT in patients with stroke is an effective treatment protocol to improve
      occupational performance and motor function. Thus, MP using AOT may be applicable
      for treating stroke patients with stroke not only while they are in the hospital
      but also at home or in the community.

PMID- 25851345
TI  - Do patients and health care professionals view the communication processes of
      clinical research differently? A Rasch analysis from a survey.
AB  - RATIONALE AIMS AND OBJECTIVES: The increasing amount of the clinical research
      conducted in the primary health care has enabled extending research beyond
      traditional settings, but this transfer has implied some trade-offs. Health care
      professionals who conduct research with trusted patients require assuming the
      ethical standards of research and communication skills to enable patients'
      autonomy and freedom of choice. This study aims to measure the opinions of health
      professionals and patients on issues of communication in clinical research.
      METHOD: A cross-sectional study with health care professionals and patients from
      primary health care centres in Barcelona (Spain). Each group completed a similar
      self-administered questionnaire. A Rasch model was fitted to data. After
      examination of goodness-of-fit, differences between groups were compared using
      analysis of variance, and patients' measures were calibrated to professionals'
      measures to compare overall mean measures. RESULTS: Professionals and patients
      found the ethical attitudes most difficult to endorse related to trust in
      clinical researchers and conflicts of interest. Patients' perceptions of
      professional ethical behaviour were significantly lower than professionals'.
      Different item functioning between nurses and family doctors was found in the
      item on seeking ethical collaboration when collaborating in clinical research.
      Effective knowledge of ethical norms was associated with greater perceived
      ethical values in clinical research and confidence in health care professionals
      among patients. CONCLUSIONS: Differences in the views of the communication
      process between patients and professionals could alert research boards, health
      care institutions and researchers to the need for greater transparency, trust and
      ethical instruction when patients are involved in clinical research.

PMID- 25851346
TI  - Synergistic effect between celecoxib and luteolin is dependent on estrogen
      receptor in human breast cancer cells.
AB  - The anti-cancer effects of celecoxib and luteolin are well known. Although our
      previous study demonstrated that the combination of celecoxib and luteolin
      synergistically inhibits breast tumor growth compared with each of the treatments
      alone, we did not uncover the molecular mechanisms of these effects. The aims of
      our present study were to compare the effects of a celecoxib and luteolin
      combination treatment in four different human breast cell lines and to determine
      the mechanisms of action in vitro and in vivo. The synergistic effects of a
      celecoxib and luteolin combination treatment yielded significantly greater cell
      growth inhibition in all four breast cancer cell lines compared with the single
      agents alone. In particular, combined celecoxib and luteolin treatment
      significantly decreased the growth of MDA-MB-231 cancer cells in vivo compared
      with either agent alone. The celecoxib and luteolin combination treatment induced
      synergistic effects via Akt inactivation and extracellular signal-regulated
      kinase (ERK) signaling inhibition in MCF-7 and MCF7/HER18 cells and via Akt
      inactivation and ERK signaling activation in MDA-MB-231 and SkBr3 cells. These
      results demonstrate the synergistic anti-tumor effect of the celecoxib and
      luteolin combination treatment in different four breast cancer cell lines, thus
      introducing the possibility of this combination as a new treatment modality.

PMID- 25851347
TI  - Upregulated TRIO expression correlates with a malignant phenotype in human
      hepatocellular carcinoma.
AB  - Triple functional domain protein (TRIO) is an evolutionarily conserved Dbl family
      guanine nucleotide exchange factors (GEFs) involved in cell proliferation and
      progression of some types of cancer. However, the expression and prognostic role
      of TRIO in hepatocellular carcinoma (HCC) have not yet been determined.
      Therefore, we attempted to determine the impact of TRIO on the clinical outcome
      of HCC patients to further identify its role in HCC. TRIO expression was examined
      using quantitative real-time PCR (qRT-PCR) and Western blotting in nonmalignant
      liver cells, HCC cells, and 93 paired of HCC tissues and adjacent noncancerous
      tissues. Statistical analyses were used to assess associations between TRIO
      expression and clinicopathological and prognostic factors. Small interfering RNA
      (siRNA)-mediated TRIO inhibition was performed in Hep3B and Huh7 cells to
      elucidate its roles in HCC. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide (MTT) assay was employed to measure cell proliferation, and apoptosis
      assay was analyzed by flow cytometry, respectively. Adhesion and transwell
      invasion assay were performed to determine the invasion ability of HCC cells in
      vitro. TRIO was significantly upregulated in the HCC cell lines and tissues
      compared with the nonmalignant liver cells and adjacent noncancerous liver
      tissues. In addition, high TRIO expression level associated with lymph node
      metastasis (P = 0.0183), clinical tumor node metastasis (TNM) stage (P =
      0.0.0106), and decrease in overall survival (OS) (P = 0.017). Knockdown of TRIO
      on Hep3B and Huh7 cell lines suppressed cell proliferation and migration and
      induced apoptosis. Furthermore, silencing TRIO expression led to decrease of ras
      related C3 botulinum toxin substrate 1 (Rac1), p-P38, B cell lymphoma 2 (BCL-2),
      and matrix metallopeptidase 9 (MMP-9). Our results demonstrated that TRIO protein
      expression is elevated and associated with a worse over survival rates in
      patients with HCC. Aberrant expression of TRIO might play an important role in
      HCC through promoting cell proliferation and invasion, and TRIO may be a novel
      therapeutic target for the treatment of HCC.

PMID- 25851348
TI  - Decreased MT1-MMP in gastric cancer suppressed cell migration and invasion via
      regulating MMPs and EMT.
AB  - Membrane type 1-matrix metalloproteinase (MT1-MMP) has been identified to play a
      significant role in several types of cancers, but little is known about the
      significance of MT1-MMP in gastric cancer patients. The purpose of this study is
      to investigate the involvement of MT1-MMP in tumor progression of gastric cancer.
      MT1-MMP expression levels were examined in gastric cancer tissues and cells, and
      normal gastric tissues and cells. The effects and molecular mechanisms of MT1-MMP
      expression on cell proliferation, migration, and invasion were also explored. In
      our results, MT1-MMP messenger RNA (mRNA) and protein expression levels were
      significantly increased in gastric cancer tissue. Moreover, the overexpression of
      MT1-MMP was positively associated with the status of clinical stage and lymph
      node metastasis through real-time PCR. Furthermore, knocking down MT1-MMP
      expression significantly suppressed the cell migration and invasion in vitro and
      regulated the expression of MMPs and epithelial-mesenchymal transition (EMT)
      associated genes. In conclusions, our study demonstrates that MT1-MMP was
      overexpressed in gastric cancer tissue, and reduced expression of MT1-MMP
      suppressed cell migration, invasion, and through regulating the expression of
      MMPs and the process of EMT in gastric cancer.

PMID- 25851349
TI  - Mdig, a lung cancer-associated gene, regulates cell cycle progression through
      p27(KIP1).
AB  - Mineral dust-induced gene (mdig) can accelerate cell proliferation. The aim of
      this study is to investigate the mechanism by which mdig regulates cell
      proliferation. A549 cells were transfected with siRNA specifically targeting
      mdig. Cell proliferation and cell cycle progression were measured using MTT assay
      and cell cycle analysis, respectively. Furthermore, real-time reverse
      transcription quantitative-polymerase chain reaction (RT-qPCR) was performed in
      A549 cells transfected with mdig siRNA to examine the expression levels of the
      cell cycle related genes such as p18(INK4c), p19(INK4d), p21(WAF/CIP1),
      p27(KIP1), p57(KIP2), cyclin D1, and cyclin E. To further explore the effect of
      mdig on p27(KIP1), the expression levels of total p27(KIP1) and its subtypes
      pT187-p27(KIP1) and pS10-p27(KIP1) were assessed by Western blotting. In vivo,
      Western blotting was performed to check the expression levels of mdig and
      p27(KIP1) in human lung cancer tissues, para-cancerous normal lung tissues, and
      para-bronchial stumps. Knockdown of mdig induced increases in p27(KIP1), both on
      mRNA and protein levels. Furthermore, the phosphorylation of p27(KIP1) at its
      Thr187 site was also inhibited. Importantly, in lung cancer tissues, upregulation
      of mdig expression accompanies with the downregulation of p27(KIP1) expression
      and in bronchial stump, vice versa. The data suggest that mdig-mediated
      inhibition of p27(KIP1) is important for cell proliferation and tumor formation
      and reveal therapeutic potential of p27(KIP1) for lung cancer.

PMID- 25851351
TI  - Walking bundles of habits (and response-outcome associations) (Commentary on
      Liljeholm et al.).

PMID- 25851350
TI  - Influence of CCND1 G870A polymorphism on the risk of HBV-related HCC and cyclin
      D1 splicing variant expression in Chinese population.
AB  - The G870A polymorphism in the exon 4/intron 4 boundary of CCND1 gene is thought
      to influence the generation of two mRNAs (cyclin D1a and cyclin D1b). The "A"
      allele codes for a truncated variant, cyclin D1b, which may have higher
      transforming activity. Herein, the tumor relevance of G870A polymorphism, the
      association between cyclin D1 variant expression and G870A genotype, and the
      oncogenic potential of cyclin D1 variants in HBV-related hepatocellular carcinoma
      (HCC) were examined. We found that there is no significant difference of G870A
      distribution among the HCC, chronic HBV (CHB) infection, cirrhotic CHB, and
      healthy control groups. Stratification analysis revealed that in younger patients
      (ages <= 50), cirrhotic CHB patients with AA genotype had an increased risk of
      developing HCC with odds ratio of 1.943 (95 % CI 1.022-3.694, p = 0.0411) as
      compared with AG/GG genotypes. The two variants were both transcripted from "A"
      and "G" alleles, and neither cyclin D1a nor D1b production was influenced by
      G870A genotype in HCC. The expression of both cyclins D1a and D1b decreased in
      HCC tissues (p = 0.003, p = 0.005), while increased in adjacent nontumor tissues
      as compared with normal liver tissues (p = 0.045, p = 0.034). Overexpression of
      cyclin D1a or D1b could promote the cell proliferation and cell-cycle progression
      in Huh-7 and LO2 cell lines. Collectively, our data suggest that G870A
      polymorphism has only very limited predictive value for HBV-related HCC. Both
      cyclins D1a and D1b could promote cell proliferation, which might contribute to
      the potential oncogenic role of cyclin D1 variants during the precancerous
      cirrhotic stage of hepatocarcinogenesis.

PMID- 25851352
TI  - Aortic and coronary aneurysms: are they really distinct entities?

PMID- 25851353
TI  - Clinical Utility of CAPE-V Sentences for Determination of Speaking Fundamental
      Frequency.
AB  - OBJECTIVES/HYPOTHESIS: Sentence stimuli from the Consensus Auditory-Perceptual
      Evaluation of Voice (CAPE-V) were compared with standard speaking fundamental
      frequency (SF0) tasks to establish clinical utility of the sentence stimuli for
      standardized assessment of SF0. STUDY DESIGN: Using a within-participant repeated
      measures design, 60 consented participants (30 males and 30 females) completed
      the study. METHODS: Participants provided 10 acoustic samples (six CAPE-V
      sentences and four additional standard tasks), counterbalanced for order effect,
      for determining SF0. A within-participant repeated measures analysis of variance
      was used in a 2 (males vs females) by 11 (10 tasks and CAPE-V sentence average)
      design to determine significant differences in SF0 with significance set at alpha
      < .05. RESULTS: Significant differences were found for the CAPE-V sentences
      "Peter will keep at the peak" and "How hard did he hit him" with seven of the
      remaining tasks and the CAPE-V average determined to be statistically similar in
      female participants. No significant differences were found for male participants.
      CONCLUSIONS: Findings from this study indicate that taken individually, four of
      the CAPE-V sentences and the average of the six CAPE-V sentences may be used
      instead of longer tasks to determine SF0 in nonvoice-disordered individuals. This
      may streamline clinical service by using the CAPE-V sentences for both
      standardized acoustic and perceptual voice assessments.

PMID- 25851354
TI  - Collagen content and distribution in the normal and transplanted human heart: A
      postmortem quantitative light microscopic analysis.
AB  - Endomyocardial biopsies in heart transplant patients offer the opportunity to
      study the myocardial interstitium in the context of myocardial function. For that
      purpose endomyocardial biopsies should reliably reflect the composition of the
      entire myocardium. We determined whether the collagen content in the
      subendocardial region of the right side of the interventricular septum (site of
      right ventricular endomyocardial biopsy), in 16 normal and 30 transplanted human
      hearts, is representative for the entire myocardium. Moreover we determined
      whether or not the mean collagen content of the myocardium is altered along with
      the posttransplantation survival time and which factors might contribute to the
      development of interstitial myocardial fibrosis. Transmural sections of the right
      and left ventricular free wall and interventricular septum were stained with
      Sirius red, which specifically stains collagen fibers. Collagen in the
      subendocardial region and central parts of the myocardium was quantified using a
      digital image analyzer. In normal hearts the mean collagen content of the
      subendocardial region of the right side of the interventricular septum (site of
      right ventricular endomyocardial biopsy) correlates well with the mean collagen
      content of the right ventricular wall and the center of the interventricular
      septum, but it does not reliably reflect the mean collagen content of the left
      ventricular free wall. In transplanted hearts the collagen content at the site of
      right ventricular endomyocardial biopsy correlates highly with the mean collagen
      content of the entire myocardium. In transplanted hearts the increase in collagen
      content is a result mainly of an increase in collagen of the left ventricular
      free wall. We conclude that in heart transplant patients, right ventricular
      endomyocardial biopsies have potential value in the analysis of the causes of
      left ventricular dysfunction. In transplanted human hearts, the
      posttransplantation survival time correlates positively with the collagen
      content, and this is attributable mainly to an increase in the collagen of the
      left ventricular free wall. 

PMID- 25851355
TI  - A practical and rapid method of histological processing for examination of
      coronary arteries containing metallic stents.
AB  - A practical and rapid method was developed to study vascular pathology after
      implantation of metal endoprostheses (stents) that are used as internal splinting
      devices of tube-like structures. This method obviates the need for time-consuming
      grinding of thick sawing sections or removal of the prosthesis prior to
      histological processing, allowing for detailed analysis of the tissue in general,
      but especially of the stent-tissue interface. The vessels, with the metal stents
      still in place, were dehydrated in graded series of ethanol and embedded in
      methyl methacrylate. Using a motor-driven rotary microtome, 3- to 5-MUm sections
      were easily cut. After deplastination, routine and special histological stainings
      were performed according to standard protocols for paraffin sections. This method
      proved to save time, compared with sawing sections, while allowing for a more
      complete examination of the stenttissue interface than is possible with routine
      paraffin techniques. 

PMID- 25851356
TI  - Congenital stenotic arteriopathy with medial dysplasia of aorta, pulmonary
      artery, and their major branches.
AB  - This report describes the morphological findings in a young child with congenital
      stenotic arteriopathy who died suddenly following arteriography. Hyperplasia of
      all of the medial components had produced severe thickening of the wall of the
      aorta (mean number of lamellar units = 133 in the thoracic aorta and 125 in the
      abdominal aorta), the pulmonary artery, and their major proximal branches,
      resulting in significant luminal narrowing. Bilateral renal artery stenosis,
      attributable mainly to intimal longitudinal smooth muscle hyperplasia associated
      with fibroelastosis, was the cause of her systemic hypertension. The left
      ventricle showed healed subendocardial infarction. 

PMID- 25851357
TI  - A fenestrated aortic valve contributing to iatrogenic aortic insufficiency post
      mitral valve replacement.
AB  - A case of an unusual local complication of cardiac valvular surgery is presented.
      Distortion of the geometry of the aortic valve base by a prosthetic mitral valve
      sewing ring allowed aortic insufficiency through the aortic valve's central
      orifice, as well as through an aortic valve cusp fenestration. During the 6 years
      after valve surgery, this patient developed chronic left heart failure
      contributed to by the aortic insufficiency and eventually, at age 65, required
      cardiac transplantation. Surgeons and pathologists should be aware of this
      unusual local complication of cardiac valve surgery, as it may have serious
      consequences. 

PMID- 25851358
TI  - Left ventricular rupture through an area of fatty infiltration: Case report and
      review of the literature.
AB  - An exceptionally rare case of left ventricular rupture through an area of fatty
      infiltration of the myocardium (lipomatosis cordis) is presented. The rupture
      occurred in a 62-year-old white woman during a dobutamine stress echo procedure.
      The autopsy revealed biventricular lipomatous infiltration with marked atrophy of
      myocardial fibers. There was no evidence of acute or old myocardial infarction.
      The literature is reviewed and pathology and clinical consequences of this
      condition are discussed. 

PMID- 25851359
TI  - Sudden death from coronary artery disease in a 28-year-old munitions worker: An
      example of stenosing intimal proliferation as an exaggerated response to injury.
AB  - A 28-year-old munitions worker died suddenly and unexpectedly early on a Monday
      morning. At autopsy, the major epicardial coronary arteries were diffusely and
      concentrically thickened, and the luminal cross-sectional area was reduced by at
      least 90%. Examination by light microscopy showed extensive intimal smooth muscle
      hyperplasia without atheroma formation. The intimal proliferation was similar to
      that reported in response to various forms of coronary artery injury, including
      balloon angioplasty, surgical endarterectomy, and chronic cardiac allograft
      vasculopathy. In addition, there was evidence of acute and chronic myocardial
      ischemia. The patient's only known risk factor for ischemic heart disease was
      occupational exposure to nitrates, in conjunction with lack of exposure on
      weekends. Although symptoms of myocardial ischemia in munitions employees are
      generally considered functional in origin (attributable to vasospasm), the
      findings in this case suggest that nitrates or, more accurately, repetitive
      nitrate withdrawal for several days at a time may also induce structural changes
      within coronary arteries. 

PMID- 25851360
TI  - External cardioversion-related cardiac damage.
AB  - Significant iatrogenic injury of the heart is an uncommon occurrence. Described
      is a unique case of electrical cardioversion injury of the heart. A 58-year-old
      man underwent orthotopic cardiac transplant for end-stage ischemic heart disease.
      Five months posttransplantation, he experienced severe acute rejection and
      developed progressive heart failure and atrial flutter, which were not responsive
      to medical treatment. The patient required external electrocardioversions, which
      were unsuccessful despite progressively increased voltage. He died of heart
      failure approximately two weeks after admission. Postmortem examination revealed
      the sequelae of acute and chronic heart failure, patchy myocardial fibrosis
      (healing rejection), ongoing mild to moderate acute rejection, and marked
      subepicardial wedge-shaped necrosis in the left ventricular free wall. The
      microscopic age of these areas was consistent with their occurrence at the time
      of attempted cardioversions, approximately seven days before death. Pathologists
      should be aware of this iatrogenic injury (and its morphologic pattern), so that
      it is not confused with ischemic or other forms of myocardial damage. 

PMID- 25851361
TI  - Myocardial toxoplasmosis complicating cardiac transplant.
AB  - The increase in numbers of immunocompromised patients has been reflected by an
      increasing frequency of opportunistic infections. Of these, Toxoplasma gondii has
      been reported as a significant human pathogen following cardiac transplantation.
      In this setting, quiescent toxoplasma myocardial cysts may become active after
      implantation into a therapeutically immunosuppressed host. The consequences of
      infection are significant and carry a high morbidity and mortality. We present
      the clinical and pathologic characteristics of a patient with toxoplasma
      infection complicating cardiac transplant and review previously reported cases of
      this entity. 

PMID- 25851362
TI  - Ultrastructural and immunohistochemical studies on myocardial biopsies from a
      patient with eosinophilic endomyocarditis.
AB  - Right ventricular endomyocardial biopsy specimens from a 13-year-old boy with
      hypereosinophilia were studied by light and electron microscopy using the EG2
      monoclonal antibody, which recognizes a common epitope of eosinophil cationic
      protein and eosinophil protein-X. Although the endocardial layer was of normal
      thickness, many eosinophils, mononuclear cells, and free eosinophil granules were
      observed in the endocardium and in the vicinity of degenerated myocardial cells.
      Under electron microscopy, many of the specific granules in and out of
      eosinophils had lost their crystalloid internae and displayed reversed density,
      and there were many degranulated eosinophils with reduced number of granules.
      Immunohistochemically, large amounts of eosinophil cationic protein and protein-X
      were observed within cardiocytes when many of them were degenerated. Deposits of
      the proteins were also found in some small vessels. On electron microscopy,
      accumulations of gold particles, which bind to eosinophil cationic protein and
      protein-X, were seen in association with specific granules and on the
      myofilaments in both degenerated and normal-appearing cardiocytes. The presence
      of eosinophil cationic proteins within cardiocytes may play an important role in
      the pathogenesis of eosinophilic endomyocardial disease. 

PMID- 25851363
TI  - Diagnosis of primary cardiac leiomyosarcoma by endomyocardial biopsy.
AB  - We report a case of a primary right ventricular leiomyosarcoma in a 58-year-old
      woman diagnosed by endomyocardial biopsy. Clinical findings included a 5-year
      history of atypical chest pain and atrial fibrillation as well as a 30-lb weight
      loss. A ventricular mass was identified by echocardiography and magnetic
      resonance imaging, and an endomyocardial biopsy was performed. Biopsy was guided
      by right ventriculography, which revealed a mobile mass in the cavity of the
      right ventricle. Light microscopy revealed a fasciculated, spindle cell sarcoma,
      most consistent with leiomyosarcoma, and immunohistochemical staining for muscle
      specific actin was strongly positive in nearly all tumor cells, confirming its
      myogenous differentiation. Endomyocardial biopsy provided a definitive tissue
      diagnosis of this rare primary malignant cardiac neoplasm without the need for a
      surgical procedure. 

PMID- 25851364
TI  - Emergent long-range synchronization of oscillating ecological populations without
      external forcing described by Ising universality.
AB  - Understanding the synchronization of oscillations across space is fundamentally
      important to many scientific disciplines. In ecology, long-range synchronization
      of oscillations in spatial populations may elevate extinction risk and signal an
      impending catastrophe. The prevailing assumption is that synchronization on
      distances longer than the dispersal scale can only be due to environmental
      correlation (the Moran effect). In contrast, we show how long-range
      synchronization can emerge over distances much longer than the length scales of
      either dispersal or environmental correlation. In particular, we demonstrate that
      the transition from incoherence to long-range synchronization of two-cycle
      oscillations in noisy spatial population models is described by the Ising
      universality class of statistical physics. This result shows, in contrast to all
      previous work, how the Ising critical transition can emerge directly from the
      dynamics of ecological populations. 

PMID- 25851365
TI  - [Every hour causes damage, the last one kills....].

PMID- 25851366
TI  - [Schistosomiasis].

PMID- 25851368
TI  - Age and gender as independent predictors of violence under the influence of
      alcohol in Zurich, Switzerland.
AB  - Violent behaviour associated with alcohol consumption is frequently reported by
      different media. Clinical data analysing the correlation between alcohol
      intoxication, age, gender and violence are scarce. The aim of this study was to
      evaluate the influence of age, gender and blood alcohol content on violent
      behaviour under the influence of alcohol under central European conditions. Three
      hundred patients admitted to the emergency department were included into this
      study in the time period from January 01. to December 31. 2009. The inclusion
      criteria were a blood alcohol content (BAC) of >=10 mmol/l, any traumatic injury
      and an age >=16 years. Violence was defined as an evitable act committed by
      others leading to patient's hospitalisation. The data were compared with Wilcoxon
      and chi2-test for proportions. The data were considered as significant if p<0,05.
      Predictive quality was evaluated by using receiver operating characteristic (ROC)
      curve. Independent predictors were analyzed by logistic regression analysis. The
      average age was 36,9+/-16,9 years (range: 16-84 years), 259 (86%) males and 41
      (24%) females. There was a significant difference in gender (odds ratio for
      gender male 2,88; CI 95%: 1,24-6,67; p<0,001) and age dependent (odds ratio for
      each year of age 0,94; CI 95%: 0,93-0,96; p<0,0001) violence with no correlation
      to blood alcohol content found. Logistic regression analysis revealed male gender
      and young age as an independent predictor for violence. These results clarify the
      relationship between alcohol, age, gender and violence and have important
      implications for municipal-level alcohol policies. 

PMID- 25851369
TI  - [Sport, is it really so good for health?].
AB  - Physical activity is necessary for life and is one of the greatest opportunities
      to improve the health of populations, although it is sometimes mixed up with
      sports which can cause injuries or acute cardiac events. Nevertheless, some
      sedentaries can present with metabolic adverse responses after initiation of a
      well-planned, health-enhancing physical activity program. This sort of exercise
      intolerance has some genetic roots and does not necessarily imply that all
      physical activity should be stopped, but rather must be considered as a side
      effect of therapy that needs optimizing. Individualization of exercise
      prescription will always consider follow-up and has to be dynamic according to
      observations made with the patient. 

PMID- 25851370
TI  - [When the tissue tolerance fiber tears].
AB  - We report a 65 year old patient who presented with both an aneurysm of the
      axillary artery and, some years later, with an acute aortic dissection type
      Stanford A. After surgical intervention of the dissection in the further workup,
      no specific etiology could be found. The most likely reason for the two aneurysms
      was the inadequately treated hypertension. Therefore, follow-up strategies aim to
      treat the risk factors which are known to promote aneurysm growth. 

PMID- 25851372
TI  - [Diagnosis of Lyme borreliosis].

PMID- 25851373
TI  - [Not Available].

PMID- 25851374
TI  - [In Process Citation].

PMID- 25851376
TI  - [Ultrasound diagnosis 63. Tumor of the bladder wall, partially necrotic
      (calcified)].

PMID- 25851378
TI  - [Personalities in the history of medicine. Sergej Sergejewitsch Korsakow. Nikolaj
      Sergejitsch Korotkow].

PMID- 25851379
TI  - Erratum to: Saliva Versus Plasma Bioequivalence of Rusovastatin in Humans:
      Validation of Class III Drugs of the Salivary Excretion Classification System.

PMID- 25851380
TI  - Response to Commentary by W. Jost on: Pharmaceutical, Biological, and Clinical
      Properties of Botulinum Neurotoxin Type A Products.

PMID- 25851381
TI  - Comment on Hamada et al.: Ultrasound assessment of gastric volume in critically
      ill patients.

PMID- 25851382
TI  - Acute ruptured mycotic aneurysm mimicking myocardial tumor with ST elevation
      myocardial infarction.

PMID- 25851383
TI  - Early physical rehabilitation in intensive care patients with sepsis syndromes: a
      pilot randomised controlled trial.
AB  - RATIONALE: Survivors of sepsis syndromes have poor outcomes for physical and
      cognitive function. No investigations of early physical rehabilitation in the
      intensive care unit have specifically targeted patients with sepsis syndromes.
      OBJECTIVE: To determine whether early physical rehabilitation improves physical
      function and associated outcomes in patients with sepsis syndromes. METHODS:
      Fifty critically ill adults admitted to a general intensive care unit with sepsis
      syndromes were recruited into a prospective double-blinded randomised controlled
      trial investigating early physical rehabilitation. MEASUREMENTS: Primary outcomes
      of physical function (acute care index of function) and self-reported health
      related quality of life were recorded at ICU discharge and 6 months post-hospital
      discharge, respectively. Secondary measures included inflammatory biomarkers;
      Interleukin-6, Interleukin-10 and tumour necrosis factor-alpha, blood lactate,
      fat-free muscle mass, exercise capacity, muscle strength and anxiety. MAIN
      RESULTS: A significant increase in patient self-reported physical function (81.8
      +/- 22.2 vs. 60.0 +/- 29.4), p = 0.04) and physical role (61.4 +/- 43.8 vs. 17.1
      +/- 34.4, p = 0.005) for the SF-36 at 6 months was found in the exercise group.
      Physical function scores were not significantly different between groups. Muscle
      strength scores were (51.9 +/- 10.5 vs. 47.3 +/- 13.6, p = 0.24) with the
      standard care mean Medical Research Council Muscle Score (MRC) <48/60. The mean
      change of Interleukin-10 increased and was significantly higher in the exercise
      group (1.8 pg/ml, 180 % vs. 0.9 pg/ml, 90 %, p = 0.04). There was no significant
      difference between groups for lactate, Interleukin-6, tumour necrosis factor
      alpha, muscle strength, exercise capacity, fat-free mass or hospital anxiety.
      CONCLUSION: Implementation of early physical rehabilitation can improve self
      reported physical function and induce systemic anti-inflammatory effects.

PMID- 25851384
TI  - Phenotypic clusters within sepsis-associated multiple organ dysfunction syndrome.
AB  - INTRODUCTION: Sepsis is a devastating condition that is generally treated as a
      single disease. Identification of meaningfully distinct clusters may improve
      research, treatment and prognostication among septic patients. We therefore
      sought to identify clusters among patients with severe sepsis or septic shock.
      METHODS: We retrospectively studied all patients with severe sepsis or septic
      shock admitted directly from the emergency department to the intensive care units
      (ICUs) of three hospitals, 2006-2013. Using age and Sequential Organ Failure
      Assessment (SOFA) subscores, we defined clusters utilizing self-organizing maps,
      a method for representing multidimensional data in intuitive two-dimensional
      grids to facilitate cluster identification. RESULTS: We identified 2533 patients
      with severe sepsis or septic shock. Overall mortality was 17 %, with a mean
      APACHE II score of 24, mean SOFA score of 8 and a mean ICU stay of 5.4 days. Four
      distinct clusters were identified; (1) shock with elevated creatinine, (2)
      minimal multi-organ dysfunction syndrome (MODS), (3) shock with hypoxemia and
      altered mental status, and (4) hepatic disease. Mortality (95 % confidence
      intervals) for these clusters was 11 (8-14), 12 (11-14), 28 (25-32), and 21 (16
      26) %, respectively (p < 0.0001). Regression modeling demonstrated that the
      clusters differed in the association between clinical outcomes and predictors,
      including APACHE II score. CONCLUSIONS: We identified four distinct clusters of
      MODS among patients with severe sepsis or septic shock. These clusters may
      reflect underlying pathophysiological differences and could potentially
      facilitate tailored treatments or directed research.

PMID- 25851385
TI  - Direct extubation onto high-flow nasal cannulae post-cardiac surgery versus
      standard treatment in patients with a BMI >=30: a randomised controlled trial.
AB  - PURPOSE: Patients with a body mass index (BMI) >=30 kg/m(2) experience more
      severe atelectasis following cardiac surgery than those with normal BMI and its
      resolution is slower. This study aimed to compare extubation of patients post
      cardiac surgery with a BMI >=30 kg/m(2) onto high-flow nasal cannulae (HFNC) with
      standard care to determine whether HFNC could assist in minimising post-operative
      atelectasis and improve respiratory function. METHODS: In this randomised
      controlled trial, patients received HFNC or standard oxygen therapy post
      extubation. The primary outcome was atelectasis on chest X-ray. Secondary
      outcomes included oxygenation, respiratory rate (RR), subjective dyspnoea, and
      failure of allocated treatment. RESULTS: One hundred and fifty-five patients were
      randomised, 74 to control, 81 to HFNC. No difference was seen between groups in
      atelectasis scores on Days 1 or 5 (median scores = 2, p = 0.70 and p = 0.15,
      respectively). In the 24-h post-extubation, there was no difference in mean
      PaO2/FiO2 ratio (HFNC 227.9, control 253.3, p = 0.08), or RR (HFNC 17.2, control
      16.7, p = 0.17). However, low dyspnoea levels were observed in each group at 8 h
      post-extubation, median (IQR) scores were 0 (0-1) for control and 1 (0-3) for
      HFNC (p = 0.008). Five patients failed allocated treatment in the control group
      compared with three in the treatment group [Odds ratio 0.53, (95 % CI 0.11,
      2.24), p = 0.40]. CONCLUSIONS: In this study, prophylactic extubation onto HFNC
      post-cardiac surgery in patients with a BMI >=30 kg/m(2) did not lead to
      improvements in respiratory function. Larger studies assessing the role of HFNC
      in preventing worsening of respiratory function and intubation are required.

PMID- 25851386
TI  - What's new on the HPA axis?

PMID- 25851387
TI  - Testing current practice is no mistake.

PMID- 25851388
TI  - Response to Perner et al.: testing current practice is no mistake.

PMID- 25851389
TI  - Venous-arterial CO2 to arterial-venous O2 difference ratio as a resuscitation
      target in shock states?

PMID- 25851390
TI  - Molding thrombus of an ECMO cannula floating in the right atrium.

PMID- 25851392
TI  - Can inferior vena cava saturations be used instead of ScvO2 in children with
      septic shock?

PMID- 25851391
TI  - Health-related quality of life following pediatric critical illness.
AB  - PURPOSE: The aims of this focused review of the literature on children surviving
      critical illness were to (1) determine whether health-related quality of life
      (HRQL) represents a clinically meaningful outcome measure for children surviving
      critical illness and (2) evaluate the HRQL measures implemented in pediatric
      critical care studies to date. METHODS: This was a focused review of the
      literature from 1980 to 2015 based on a search of EMBASE/PubMed, MEDLINE and
      PsycInfo assessing trends and determinants of HRQL outcomes in children surviving
      critical illness. We also evaluated the psychometric properties of the HRQL
      instruments used in the studies identified by examining each measure's reported
      reliability, validity and sensitivity to clinical change. RESULTS: The literature
      search identified 253 pediatric articles for potential inclusion in the review,
      among which data from 78 studies were ultimately selected for inclusion. Of the
      22 measures utilized in the studies reviewed, only four demonstrated excellent
      psychometric properties for use in pediatric critical care trials. Trends in HRQL
      identified in the studies reviewed suggest significant ongoing morbidity for
      children surviving critical illness. Key determinants of poor HRQL outcomes
      include reason for PICU admission (sepsis, meningoencephalitis, trauma),
      antecedents (chronic comorbid conditions), treatments received (prolonged
      cardiopulmonary resuscitation, long-stay patients, invasive technology),
      psychological outcomes (post-traumatic stress disorder, parent
      anxiety/depression) and social and environmental characteristics (low
      socioeconomic status, parental education and functioning). CONCLUSIONS: Validated
      pediatric HRQL instruments are now available. Significant impact on HRQL has been
      demonstrated in acute and acute on chronic critical illness. Future pediatric
      critical care interventional trials should include both mortality as well as long
      term HRQL measurements to truly ascertain the full impact of critical illness in
      children.

PMID- 25851393
TI  - Checklist use in ICUs: a French national survey.

PMID- 25851394
TI  - Erratum to: Diastolic dysfunction and mortality in septic patients: a systematic
      review and meta-analysis.

PMID- 25851395
TI  - Vasculitis unlimited in rheumatoid arthritis an illustrated review.
AB  - Rheumatoid arthritis has a multitude of extra-articular manifestations, of which
      systemic vasculitis is a clinically significant co-morbidity and co-mortality
      determinant in the prognosis of the disease. Rheumatoid vasculitis may occur in
      the early stage of the disease but, more commonly, in patients who have had
      seropositive rheumatoid arthritis for 10 years or longer. Rheumatoid vasculitis
      has a wide variety of histopathologic expressions and it may affect blood vessels
      of all sizes (from vasa nervorum or vasa vasorum to the aorta; and occasionally
      veins and venules). The diagnosis ideally requires biopsy or autopsy tissue
      confirmation, which is discussed and illustrated in this review. 

PMID- 25851396
TI  - Mitochondrial DNA defects in cardiomyopathy.
AB  - Abnormalities in mitochondrial DNA (mtDNA) including specific deletions and point
      mutations have been found in an increasing number of cases of both dilated and
      hypertrophic cardiomyopathy. The role that these mutations may play in
      contributing to the cardiomyopathic phenotype is discussed in this survey of the
      recent literature. 

PMID- 25851397
TI  - Pathogenesis of cardiomyopathy caused by anthracycline antibiotics effect of
      pulmonary stenosis on the development of cardiomyopathy.
AB  - This study was undertaken to elucidate the effect of pressure load on the
      development of cardiomyopathy induced by daunorubicin in the right ventricle of
      rabbits on which pulmonary stenosis had been performed. The right ventricular
      pressure after occlusion of the pulmonary artery was approximately twice that
      prior to occlusion. Pulmonary stenosis apparently produced hypertrophy of the
      right ventricular myocardium within approximately 2 weeks of occlusion. In
      rabbits with pulmonary stenosis, the characteristic myocardial degenerative
      changes induced by daunorubicin were found on the right ventricular wall.
      However, in rabbits without pulmonary stenosis, myocardial lesions were observed
      only on the left ventricular wall. The pressure load acting as a mechanical
      stress increases myocardial damage induced by daunorubicin. It is well known that
      anthracyclines take effect on cells in which nucleic acid synthesis is augmented
      and the pressure load results in the enhancement of protooncogene expression in
      myocytes and a subsequent increase in protein synthesis. These results suggest
      that the pressure load may play a significant role in anthracycline
      cardiomyopathy by increasing protein synthesis in the myocardium. 

PMID- 25851398
TI  - Co-localization of fibrinolytic activators and inhibitors with macrophages in
      atherosclerotic vessels.
AB  - The plasmin system is involved in hemostasis and tissue remodelling. The
      accumulation of plasminogen activators and their inhibitors in atherosclerotic
      lesions may be due to invasion of inflammatory cells in the vessel wall. High
      concentrations of macrophages are associated with increased risk of
      atherosclerotic plaque rupture. By immunohistochemistry on circumferential serial
      sections of atherosclerotic and healthy vessels the morphological association of
      plasminogen activators and inhibitors with macrophages was studied. Urokinase
      plasminogen activator (u-PA), plasminogen activator inhibitor type 2 (PAI-2), and
      macrophages were mainly expressed within plaques while tissue plasminogen
      activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) were also
      expressed outside plaque lesions. Computer assisted image analysis on diseased
      vessels showed that regulatory proteins of the fibrinolytic system were found
      more often in areas positive for macrophages than in other parts of the sections
      (p < 0.001). u-PA was significantly more defined to areas positive for
      macrophages than tissue plasminogen activator (t-PA) and plasminogen activator
      inhibitor type 1 (PAI-1) (p < 0.05). Similarly, PAI-2 expression was more
      associated with macrophage distribution than PAI-1 (p < 0.05). Tumor necrosis
      factor alpha (TNFalpha), an inflammatoric mediator of macrophages, had the same
      levels of co-localization with macrophages as u-PA and PAI-2. These results
      suggest that u-PA and PAI-2 might be key factors for inflammatory regulation of
      plasmin mediated proteolysis in the vessel walls. 

PMID- 25851399
TI  - Acid hydrolyzable aldehydes in long-term stored commercial bioprosthetic heart
      valves implications for calcification.
AB  - There is evidence that glutaraldehyde used routinely in the fixation process of
      bioprosthetic heart valves may be a major factor in their subsequent
      calcification. A further complication is introduced by the use of a formaldehyde
      treatment step, whether for sterilization or storage. The effects of this second
      aldehyde on calcification is also unknown. The aim of the present work is to
      determine the degree of glutaraldehyde and formaldehyde incorporation into
      commercial valve leaflets and to establish whether there is a relationship
      between the aldehyde treatment and tissue calcification. Both pre- and post
      implantation concentrations of aldehydes were estimated by high performance
      liquid chromatography of acid hydrolyzates of commercial valve tissue. Control
      samples were taken from freshly prepared porcine aortic valves and bovine
      pericardium fixed in glutaraldehyde. The degree of calcification was investigated
      using the rat subcutaneous implant model. Samples were retrieved after 56 days
      and calcium estimated by atomic absorption spectroscopy. The results indicated
      that storage of both porcine and pericardial valves for periods of 5 years or
      longer reduced calcification. A greater reduction in calcification was noted when
      tissue was treated sequentially with glutaraldehyde and formaldehyde rather than
      glutaraldehyde alone. From this work it can be concluded that bioprosthetic
      valves calcify less in the rat model when they are stored for extended periods of
      time in glutaraldehyde solution. This effect is enhanced when formaldehyde
      storage is employed. 

PMID- 25851400
TI  - Conditions associated with extreme hyperferritinaemia (>3000 MUg/L) in adults.
AB  - BACKGROUND: The clinical significance of extreme hyperferritinaemia has come
      under scrutiny with the increasing recognition of haemophagocytic
      lymphohistiocytosis (HLH) in adults. Most studies of hyperferritinaemia have
      focused on serum ferritin greater than 1000 MUg/L, often in ambulatory patients.
      The conditions associated with more extreme hyperferritinaemia are poorly
      understood. AIMS: To examine conditions associated with extreme
      hyperferritinaemia greater than 3000 MUg/L in acutely ill adults at a quaternary
      care hospital. METHODS: Patients with serum ferritin greater than 3000 MUg/L at
      Vancouver General Hospital between 1 August 2011 and 1 August 2012 were
      identified. Those over 18 years of age and with clinical data available were
      included in the study. RESULTS: Eighty-three subjects were identified. Twenty-one
      cases (25%) were due to transfusional iron overload, 16 (19%) due to liver
      disease and 15 (18%) due to mixed factors. Haemophagocytic lymphohistiocytosis
      (HLH) was diagnosed in six of 83 patients (7%) with ferritin greater than 3000
      MUg/L, but six of eight patients (75%) with ferritin greater than 20 000 MUg/L.
      CONCLUSIONS: Extreme hyperferritinaemia greater than 3000 MUg/L is uncommon in
      adult patients. The highest serum ferritin values are seen in HLH, but the
      differential diagnosis for serum ferritin greater than 3000 MUg/L remains broad
      with iron overload and liver disease being the most common causes.

PMID- 25851401
TI  - Approaching the alloy limit of thermal conductivity in single-crystalline Si
      based thermoelectric nanocomposites: A molecular dynamics investigation.
AB  - Single-crystalline Si-based nanocomposites have become promising candidates for
      thermoelectric applications due to their prominent merits. Reducing the thermal
      conductivity kappa without deteriorating the electrical properties is the key to
      improve their performance. Through non-equilibrium molecular dynamics
      simulations, we show that kappa of single-crystalline Si-based nanocomposites can
      be reduced to the alloy limit by embedding various nanoinclusions of similar
      lattice constants but different lattice orientations or space symmetries with
      respect to the matrix. The surprisingly low kappa is mainly due to the large
      acoustic phonon density of states mismatch caused by the destruction of lattice
      periodicity at the interfaces between the nanoinclusions and matrix, which leads
      to the substantial reduction of phonon group velocity and relaxation time, as
      well as the enhancement of phonon localization. The resulting kappa is also
      temperature-insensitive due to the dominance of boundary scattering. The increase
      in thermal resistance induced by lattice structure mismatch mainly comes from the
      nanoinclusions and the channels between them and is caused by the enhanced
      boundary scattering at the interfaces parallel to the heat flux. Approaching the
      alloy limit of kappa with potentially improved electrical properties by fillers
      will remarkably improve ZT of single-crystalline Si-based nanocomposites and
      extend their application. 

PMID- 25851402
TI  - Magnetic resonance imaging has no role in diagnosing the origin of pain in
      patients with overwhelmingly painful inguinal hernia.
AB  - PURPOSE: Clinical tools for predicting postoperative pain should be developed to
      provide better care for patients. The aims of this study were to evaluate
      preoperative magnetic resonance imaging (MRI) findings to reveal reasons for
      overwhelming pain in patients with inguinal hernia and to detect changes in
      quality-of-life (QoL) and pain scores preoperatively and following laparoscopic
      totally extraperitoneal (TEP) repair of inguinal hernia. METHODS: Twenty-two
      patients aged 18-50 years presenting with extremely painful inguinal hernias
      (highest pain scores >50, scale 0-100) were examined with MRI prior to operative
      treatment with TEP repair. Postoperative follow-up lasted 6 months and consisted
      of questionnaires regarding functional status, pain, QoL and possible
      complications. Postoperative MRI scans were performed only in cases of
      preoperative findings on the MRI or prolonged inguinal pain persisting over 6
      months. RESULTS: Prolonged postoperative pain could not be predicted from
      preoperative MRI scans, because no signs of the pain's origin such as pubic
      periostal irritation, bone marrow edema, pelvic bone or hip joint abnormalities,
      or lower abdominal muscle hemorrhage were detected in MRI. TEP repair of inguinal
      hernia significantly improved the patients' quality of life and relieved pain
      symptoms. High preoperative pain scores were major predictors of prolonged
      postoperative pain. CONCLUSIONS: Carefully evaluated preoperative pelvic MRI was
      usually normal in patients with high pain scores prior to operation. Preoperative
      pain scores may serve as indicators of development of prolonged inguinal pain.

PMID- 25851403
TI  - Anti-diabetic therapies and the risk of acute pancreatitis: a nationwide
      retrospective cohort study from Taiwan.
AB  - AIMS: To examine the relationship between different anti-diabetic therapies
      (dipeptidyl peptidase-4 (DPP-4), metformin and sulfonylureas) and risk of acute
      pancreatitis among type 2 diabetic patients in Taiwan, and explore each drug's
      dose-response relationship. MATERIALS AND METHODS: We derived a nationwide
      retrospective cohort of patients with type 2 diabetes in Taiwan. The inclusion
      criteria are adult diabetic patients with continuous baseline enrollment, new
      users of the studied drugs, and without missing demographics. There were 4113/101
      498/44 772 DPP-4/Metformin/Sulfonylurea users. Adjusted hazards ratios for
      pancreatitis associated with DPP-4, derived from Cox proportional hazard models
      with propensity score weighting, were estimated; dose-response analyses were also
      conducted. RESULTS: Dipeptidyl peptidase-4 was statistically significantly
      associated with a decreased risk of acute pancreatitis compared with
      sulfonylureas (adjusted HR: 0.36, 95%CI [0.17, 0.75]) but not metformin (adjusted
      HR: 0.67, 95%CI [0.32, 1.41]); metformin was statistically significantly
      associated with a lower risk of pancreatitis than sulfonylurea (adjusted HR: 0.
      53; 95%CI [0.37, 0.76]). In addition, low-dose metformin was statistically
      significantly associated with a lower risk of pancreatitis compared with high
      dose metformin (HR: 0.65; 95%CI [0.44, 0.97]). CONCLUSIONS: Our findings suggest
      that sulfonylureas may potentially be associated with an increased risk of
      pancreatitis compared with DPP-4 or metformin. Studies with longer follow up,
      larger sample sizes, and more precise capture of confounders may be needed to
      determine the risk of pancreatitis associated with incretin based therapies.

PMID- 25851404
TI  - [Fine-needle aspiration in an extremely late post-traumatic iris cyst].
AB  - CLINICAL CASE: A 45 year-old woman with unknown ophthalmology history complained
      of pain, redness and visual acuity (VA) loss in her left eye for the last three
      weeks. A serous iris cyst with an overlying peripheral corneal leukoma was
      located in the iris stroma using ultrasonic biomicroscopy. It was assumed that it
      was secondary to a penetrating trauma from her childhood. The cyst healed and VA
      improved after fine-needle aspiration and partial posterior synechiolysis.
      DISCUSSION: Iris inclusion cysts may appear many years after penetrating trauma
      or surgery. Fine-needle aspiration is a good choice for its diagnosis and
      treatment.

PMID- 25851405
TI  - Zero-profile integrated plate and spacer device reduces rate of adjacent-level
      ossification development and dysphagia compared to ACDF with plating and cage
      system.
AB  - STUDY DESIGN: Retrospective case-control study. PURPOSE: To compare the safety
      and efficacy of the Zero-profile (Zero-p) integrated plate and spacer device to
      that of an anterior cervical plate and cage in patients undergoing anterior
      cervical discectomy and fusion (ACDF). Anterior cervical plating system has
      provided good results, including higher fusion rate and improved alignment since
      its use. However, adjacent-level ossification development (ALOD) and dysphagia
      have been usually reported associating with plates. METHODS: This was a
      retrospective control study. Sixty-two patients with cervical radiculopathy or
      myelopathy were treated with an anterior plate and cage or Zero-p implant between
      January 2011 and December 2011. The mean follow-up was 33.1 months in the plate
      and cage group and 30.6 months in Zero-p group. Patient demographics, operative
      details and complications were reviewed. The clinical outcomes were evaluated
      using the Japanese Orthopaedic Association (JOA) scores and JOA recovery rate
      before and after operations. Incidence of cephalad and caudal ALOD on the lateral
      radiographs was studied at preoperation, immediate postoperation and last follow
      up. Incidence of dysphagia was also recorded after operation according to Bazaz
      Yoo dysphagia index. RESULTS: Thirty-two patients received an anterior plate and
      cage and 30 received the Zero-p implant. There were no statistical differences in
      patient demographics, operative details between the two groups. The JOA scores
      significantly increased compared with preoperational measurements in both groups
      (p < 0.05), but the JOA recovery rate was similar (72.2 % for plate and cage
      group and 77.0 % for Zero-p group, p > 0.05). ALOD occurred in 12 (18.8 %) of the
      64 cephalad and caudal adjacent segments in plate with cage group, and only 1
      (1.6 %) of 63 adjacent levels (including three noncontiguous cases) presented
      with ALOD in Zero-p group. The difference was significant (p < 0.01). The
      incidence of dysphagia in the Zero-p group was lower compared with that in the
      plate with cage group, and the symptom duration was much shorter (p < 0.01). Both
      groups had no adverse events associated with the implant or implant surgery.
      CONCLUSIONS: The Zero-profile implant is safe and efficacious after ACDF. It can
      reduce the rate of adjacent-level ossification development and dysphagia compared
      to anterior plate and cage.

PMID- 25851406
TI  - How salinity and temperature combine to affect physiological state and
      performance in red knots with contrasting non-breeding environments.
AB  - Migratory shorebirds inhabit environments that may yield contrasting salinity
      temperature regimes-with widely varying osmoregulatory demands, even within a
      given species-and the question is: by which physiological means and at which
      organisational level do they show adjustments with respect to these demands? Red
      knots Calidris canutus winter in coastal areas over a range of latitudes. The
      nominal subspecies winters in salty areas in the tropics, whereas the subspecies
      Calidris canutus islandica winters in north-temperate regions of comparatively
      lower salinities and temperatures. In this study, both subspecies of red knot
      were acclimated to different salinity (28/400/00)-temperature (5/35  degrees C)
      combinations for 2-week periods. We then measured food/salt intakes, basal
      metabolic rate (BMR), body mass and temperature, fat and salt gland scores,
      gizzard mass, heat-shock proteins, heterophils/lymphocytes (H/L) ratio and plasma
      Na(+) to assess the responses of each taxon to osmoregulatory challenges. High
      salinity (HS)-warm-acclimated birds reduced food/salt intake, BMR, body mass, fat
      score and gizzard mass, showing that salt/heat loads constrained energy
      acquisition rates. Higher salt gland scores in saltier treatments indicated that
      its size was adjusted to higher osmoregulatory demands. Elevated plasma Na(+) and
      H/L ratio in high-salinity-warm-acclimated birds indicated that salt/heat loads
      might have a direct effect on the water-salt balance and stress responses of red
      knots. Subspecies had little or no effect on most measured parameters, suggesting
      that most adjustments reflect phenotypic flexibility rather than subspecific
      adaptations. Our results demonstrate how salinity and temperature affect various
      phenotypic traits in a migrant shorebird, highlighting the importance of
      considering these factors jointly when evaluating the environmental tolerances of
      air-breathing marine taxa.

PMID- 25851407
TI  - Eumelanin 3D Architectures: Electrospun PLA Fiber Templating for Mammalian
      Pigment Microtube Fabrication.

PMID- 25851409
TI  - Effectiveness and safety of a prehospital program of continuous positive airway
      pressure (CPAP) in an urban setting - ERRATUM.

PMID- 25851410
TI  - Multilayered Thin Films from Boronic Acid-Functional Poly(amido amine)s.
AB  - PURPOSE: To investigate the properties of phenylboronic acid-functional
      poly(amido amine) polymers (BA-PAA) in forming multilayered thin films with
      poly(vinyl alcohol) (PVA) and chondroitin sulfate (ChS), and to evaluate their
      compatibility with COS-7 cells. METHODS: Copolymers of phenylboronic acid
      functional poly(amido amine)s, differing in the content of primary amine (DAB-BA
      PAA) or alcohol (ABOL-BA-PAA) side groups, were synthesized and applied in the
      formation of multilayers with PVA and ChS. Biocompatibility of the resulting
      films was evaluated through cell culture experiments with COS-7 cells grown on
      the films. RESULTS: PVA-based multilayers were thin, reaching ~100 nm at 10
      bilayers, whereas ChS-based multilayers were thick, reaching ~600 nm at the same
      number of bilayers. All of the multilayers are stable under physiological
      conditions in vitro and are responsive to reducing agents, owing to the presence
      of disulfide bonds in the polymers. PVA-based films were demonstrated to be
      responsive to glucose at physiological pH at the investigated glucose
      concentrations (10-100 mM). The multilayered films displayed biocompatibility in
      cell culture experiments, promoting attachment and proliferation of COS-7 cells.
      CONCLUSIONS: Responsive thin films based on boronic acid functional poly(amido
      amine)s are promising biocompatible materials for biomedical applications, such
      as drug releasing surfaces on stents or implants. Graphical Abstract Layer-by
      Layer Assembly.

PMID- 25851412
TI  - Optimized leaf ordering with class labels for hierarchical clustering.
AB  - Hierarchical clustering is extensively used in the bioinformatics community to
      analyze biomedical data. These data are often tagged with class labels, as e.g.
      disease subtypes or gene ontology (GO) terms. Heatmaps in connection with
      dendrograms are the common standard to visualize results of hierarchical
      clustering. The heatmap can be enriched by an additional color bar at the side,
      indicating for each instance in the data set to which class it belongs. In the
      ideal case, when the clustering matches perfectly with the classes, one would
      expect that instances from the same class cluster together and the color bar
      consists of well-separated color blocks without frequent alteration of colors
      (classes). But even in the case when instances from the same class cluster
      perfectly together, the dendrogram might not reflect this important aspect due to
      the fact that its representation is not unique. In this paper, we propose a leaf
      ordering algorithm for the dendrogram that preserving the hierarchical clustering
      result tries to group instances from the same class together. It is based on the
      concept of dynamic programming which can efficiently compute the optimal or
      nearly optimal order, consistent with the structure of the tree. 

PMID- 25851408
TI  - Furan-based benzene mono- and dicarboxylic acid derivatives as multiple
      inhibitors of the bacterial Mur ligases (MurC-MurF): experimental and
      computational characterization.
AB  - Bacterial resistance to the available antibiotic agents underlines an urgent need
      for the discovery of novel antibacterial agents. Members of the bacterial Mur
      ligase family MurC-MurF involved in the intracellular stages of the bacterial
      peptidoglycan biosynthesis have recently emerged as a collection of attractive
      targets for novel antibacterial drug design. In this study, we have first
      extended the knowledge of the class of furan-based benzene-1,3-dicarboxylic acid
      derivatives by first showing a multiple MurC-MurF ligase inhibition for
      representatives of the extended series of this class. Steady-state kinetics
      studies on the MurD enzyme were performed for compound 1, suggesting a
      competitive inhibition with respect to ATP. To the best of our knowledge,
      compound 1 represents the first ATP-competitive MurD inhibitor reported to date
      with concurrent multiple inhibition of all four Mur ligases (MurC-MurF).
      Subsequent molecular dynamic (MD) simulations coupled with interaction energy
      calculations were performed for two alternative in silico models of compound 1 in
      the UMA/D-Glu- and ATP-binding sites of MurD, identifying binding in the ATP
      binding site as energetically more favorable in comparison to the UMA/D-Glu
      binding site, which was in agreement with steady-state kinetic data. In the final
      stage, based on the obtained MD data novel furan-based benzene monocarboxylic
      acid derivatives 8-11, exhibiting multiple Mur ligase (MurC-MurF) inhibition with
      predominantly superior ligase inhibition over the original series, were
      discovered and for compound 10 it was shown to possess promising antibacterial
      activity against S. aureus. These compounds represent novel leads that could by
      further optimization pave the way to novel antibacterial agents. 

PMID- 25851411
TI  - Distinguishing bipolar from unipolar depression: the importance of clinical
      symptoms and illness features.
AB  - BACKGROUND: Distinguishing bipolar disorder (BP) from major depressive disorder
      (MDD) has important relevance for prognosis and treatment. Prior studies have
      identified clinical features that differ between these two diseases but have been
      limited by heterogeneity and lack of replication. We sought to identify
      depression-related features that distinguish BP from MDD in large samples with
      replication. METHOD: Using a large, opportunistically ascertained collection of
      subjects with BP and MDD we selected 34 depression-related clinical features to
      test across the diagnostic categories in an initial discovery dataset consisting
      of 1228 subjects (386 BPI, 158 BPII and 684 MDD). Features significantly
      associated with BP were tested in an independent sample of 1000 BPI cases and
      1000 MDD cases for classifying ability in receiver operating characteristic (ROC)
      analysis. RESULTS: Seven clinical features showed significant association with
      BPI compared with MDD: delusions, psychomotor retardation, incapacitation,
      greater number of mixed symptoms, greater number of episodes, shorter episode
      length, and a history of experiencing a high after depression treatment. ROC
      analyses of a model including these seven factors showed significant evidence for
      discrimination between BPI and MDD in an independent dataset (area under the
      curve = 0.83). Only two features (number of mixed symptoms, and feeling high
      after an antidepressant) showed an association with BPII versus MDD. CONCLUSIONS:
      Our study suggests that clinical features distinguishing depression in BPI versus
      MDD have important classification potential for clinical practice, and should
      also be incorporated as 'baseline' features in the evaluation of novel diagnostic
      biomarkers.

PMID- 25851413
TI  - Transforming communication and safety culture in intrapartum care: a multi
      organization blueprint.
AB  - Effective, patient-centered communication facilitates interception and correction
      of potentially harmful conditions and errors. All team members, including women,
      their families, physicians, midwives, nurses, and support staff, have roles in
      identifying the potential for harm during labor and birth. However, the results
      of collaborative research studies conducted by organizations that represent
      professionals who care for women during labor and birth indicate that health care
      providers may frequently witness, but may not always report, problems with safety
      or clinical performance. Some of these health care providers felt resigned to the
      continuation of such problems and fearful of retribution if they tried to address
      them. Speaking up to address safety and quality concerns is a dynamic social
      process. Every team member must feel empowered to speak up about concerns without
      fear of put-downs, retribution, or receiving poor-quality care. Patient safety
      requires mutual accountability: individuals, teams, health care facilities, and
      professional associations have a shared responsibility for creating and
      sustaining environments of mutual respect and engaging in highly reliable
      perinatal care. Defects in human factors, communication, and leadership have been
      the leading contributors to sentinel events in perinatal care for more than a
      decade. Organizational commitment and executive leadership are essential to
      creating an environment that proactively supports safety and quality. The problem
      is well-known; the time for action is now. 

PMID- 25851414
TI  - Mutations in FARS2 and non-fatal mitochondrial dysfunction in two siblings.
AB  - Recently, mutations in FARS2, which encodes for mitochondrial phenylalanyl-tRNA
      synthetase, have been implicated in autosomal recessive combined oxidative
      phosphorylation deficiency 14. Associated clinical features in three previously
      reported patients with confirmed FARS2 mutations include infantile onset
      epilepsy, and a fatal Alpers-like encephalopathy. Herein, we report on two
      siblings with global developmental delay, dysarthria and tremor and compound
      heterozygous FARS2 abnormalities. They have a heterozygous missense mutation,
      c.1255C>T which predicts p.Arg419Cys in exon 7 of FARS2, inherited from their
      father and uncovered on exome sequencing, and an interstitial deletion of
      chromosome 6p25.1 inherited from their mother and uncovered on SNP array. This
      interstitial deletion includes all of exon 6 and parts of introns 5 and 6 of
      FARS2. Biochemical studies were also consistent with a mitochondrial disorder.
      While these siblings had considerable developmental difficulties, they are making
      consistent developmental progress and appear to be considerably less severely
      affected than the other patients reported in the literature with FARS2 associated
      mitochondrial disease. Thus, this study expands the phenotypic spectrum of FARS2
      related disease and emphasizes intragenic deletion in the list of causative
      mutations.

PMID- 25851416
TI  - Persistence of Phrenic Nerve Palsy Following 28-mm Cryoballoon Ablation: A Four
      Year Single Center Experience.
AB  - BACKGROUND: Phrenic nerve palsy (PNP) is the most frequently observed
      complication in the setting of cryoballoon (CB) ablation (Arctic Front, Medtronic
      Inc., Minneapolis, MN, USA). Although, usually transient, resolving before the
      end of the procedure, persistent PNP (not resolving before the end of procedure)
      can occur. Literature on persistent PNP after second generation CB ablation is
      relatively sparse. METHODS: A total of 316 consecutive patients having undergone
      large 28-mm CB ablation as index procedure in the Heart Rhythm Management Center,
      UZ Brussels, Belgium, from January 2009 to December 2013 were retrospectively
      reviewed for the study. Of these 117 patients were treated with the first
      generation CB (CB1) and 199 patients with the second generation CB (CB2).
      RESULTS: PNP occurred in 10% of the total population. Persistent PNP was only
      observed following CB2 ablation which occurred in 4.5% of the group. At a mean
      follow-up of 11 months, diaphragmatic contraction in persistent PNP patients
      resumed in 78% (7/9) of the patients. In a final follow-up at 5 and 20 months,
      PNP persisted in two patients, respectively. PNP during ablation in the right
      inferior pulmonary vein was only observed in the CB2 group. No predictors of
      persistency of PNP were observed. CONCLUSION: Persistence of PNP only occurred in
      the CB2 group in 4.5% of patients. The majority of patients with persistent PNP
      were asymptomatic. In most of the patients having persistent PNP after ablation,
      complete phrenic nerve function resumed during follow-up (78%).

PMID- 25851417
TI  - Conflicts of interest in research: looking out for number one means keeping the
      primary interest front and center.
AB  - Conflicts of interest represent circumstances in which professional judgments or
      actions regarding a primary interest, such as the responsibilities of a medical
      researcher, may be at risk of being unduly influenced by a secondary interest,
      such as financial gain or career advancement. The secondary interest may be
      financial or non-financial, and the resultant bias may be conscious or
      unconscious. The presence of conflicts of interest poses a problem for
      professional, patient, and public trust in research and the research enterprise.
      Effective means of identifying and managing conflicts are an important element in
      successfully achieving the goals of research. These strategies typically focus on
      the investigator and rely upon disclosure, which has substantial limitations.
      Additional management strategies include process-oriented steps and outcomes
      oriented strategies. More attention to identifying and managing non-financial
      conflicts is needed. Future empirical research will be important for defining
      which conflicts need to be better addressed and how to achieve this goal. 

PMID- 25851415
TI  - Hemophilia B: molecular pathogenesis and mutation analysis.
AB  - Hemophilia B is an X-chromosome-linked inherited bleeding disorder primarily
      affecting males, but those carrier females with reduced factor IX activity
      (FIX:C) levels may also experience some bleeding. Genetic analysis has been
      undertaken for hemophilia B since the mid-1980s, through linkage analysis to
      track inheritance of an affected allele, and to enable determination of the
      familial mutation. Mutation analysis using PCR and Sanger sequencing along with
      dosage analysis for detection of large deletions/duplications enables mutation
      detection in > 97% of patients with hemophilia B. The risk of the development of
      inhibitory antibodies, which are reported in ~ 2% of patients with hemophilia B,
      can be predicted, especially in patients with large deletions, and these
      individuals are also at risk of anaphylaxis, and nephrotic syndrome if they
      receive immune tolerance induction. Inhibitors also occur in patients with
      nonsense mutations, occasionally in patients with small insertions/deletions or
      splice mutations, and rarely in patients with missense mutations (p.Gln237Lys and
      p.Gln241His). Hemophilia B results from several different mechanisms, and those
      associated with hemophilia B Leyden, ribosome readthrough of nonsense mutations
      and apparently 'silent' changes that do not alter amino acid coding are explored.
      Large databases of genetic variants in healthy individuals and patients with a
      range of disorders, including hemophilia B, are yielding useful information on
      sequence variant frequency to help establish possible variant pathogenicity, and
      a growing range of algorithms are available to help predict pathogenicity for
      previously unreported variants. 

PMID- 25851419
TI  - Breakage of two silicone endotracheal tubes during extubation.
AB  - Silicone endotracheal tubes broke during tracheal extubation of two dogs after
      uneventful anaesthesia. The remaining pieces were removed via endoscopy, and both
      dogs recovered with no further problems. A third silicone endotracheal tube broke
      while checking for cracks prior to its use. Biofilm formation on the surface of
      the endotracheal tube is thought to be the main cause of the breakage.
      Destruction of the biofilm is difficult, therefore exhaustive cleaning with
      detergents followed by vigorous brushing is recommended to break the interaction
      between the silicone surface and the biofilm. It is suggested that careful
      attention is paid to how tubes are cleaned and dried (in a hanging position), and
      that they are checked carefully for cracks prior to each use. 

PMID- 25851420
TI  - Dual Element Intercalation into 2D Layered Bi2Se3 Nanoribbons.
AB  - We demonstrate the intercalation of multiple zero-valent atomic species into two
      dimensional (2D) layered Bi2Se3 nanoribbons. Intercalation is performed
      chemically through a stepwise combination of disproportionation redox reactions,
      hydrazine reduction, or carbonyl decomposition. Traditional intercalation is
      electrochemical thus limiting intercalant guests to a single atomic species. We
      show that multiple zero-valent atoms can be intercalated through this chemical
      route into the host lattice of a 2D crystal. Intermetallic species exhibit unique
      structural ordering demonstrated in a variety of superlattice diffraction
      patterns. We believe this method is general and can be used to achieve a wide
      variety of new 2D materials previously inaccessible. 

PMID- 25851418
TI  - Curvature sensing MARCKS-ED peptides bind to membranes in a stereo-independent
      manner.
AB  - Membrane curvature and lipid composition plays a critical role in interchanging
      of matter and energy in cells. Peptide curvature sensors are known to activate
      signaling pathways and promote molecular transport across cell membranes.
      Recently, the 25-mer MARCKS-ED peptide, which is derived from the effector domain
      of the myristoylated alanine-rich C kinase substrate protein, has been reported
      to selectively recognize highly curved membrane surfaces. Our previous studies
      indicated that the naturally occurring L-MARCKS-ED peptide could simultaneously
      detect both phosphatidylserine and curvature. Here, we demonstrate that D-MARCKS
      ED, composed by unnatural D-amino acids, has the same activities as its
      enantiomer, L-MARCKS-ED, as a curvature and lipid sensor. An atomistic molecular
      dynamics simulation suggests that D-MARCKS-ED may change from linear to a boat
      conformation upon binding to the membrane. Comparable enhancement of fluorescence
      intensity was observed between D- and L-MARCKS-ED peptides, indicating similar
      binding affinities. Meanwhile, circular dichroism spectra of D- and L-MARCKS-ED
      are almost symmetrical both in the presence and absence of liposomes. These
      results suggest similar behavior of artificial D- and natural L-MARCKS-ED
      peptides when binding to curved membranes. Our studies may contribute to further
      understanding of how MARCKS-ED senses membrane curvature as well as provide a new
      direction to develop novel membrane curvature probes.

PMID- 25851422
TI  - Erratum.

PMID- 25851421
TI  - Diet rich in high glucoraphanin broccoli reduces plasma LDL cholesterol: Evidence
      from randomised controlled trials.
AB  - SCOPE: Cruciferous-rich diets have been associated with reduction in plasma LDL
      cholesterol (LDL-C), which may be due to the action of isothiocyanates derived
      from glucosinolates that accumulate in these vegetables. This study tests the
      hypothesis that a diet rich in high glucoraphanin (HG) broccoli will reduce
      plasma LDL-C. METHODS AND RESULTS: One hundred and thirty volunteers were
      recruited to two independent double-blind, randomly allocated parallel dietary
      intervention studies, and were assigned to consume either 400 g standard broccoli
      or 400 g HG broccoli per week for 12 weeks. Plasma lipids were quantified before
      and after the intervention. In study 1 (37 volunteers), the HG broccoli diet
      reduced plasma LDL-C by 7.1% (95% CI: -1.8%, -12.3%, p = 0.011), whereas standard
      broccoli reduced LDL-C by 1.8% (95% CI +3.9%, -7.5%, ns). In study 2 (93
      volunteers), the HG broccoli diet resulted in a reduction of 5.1% (95% CI: -2.1%,
      -8.1%, p = 0.001), whereas standard broccoli reduced LDL-C by 2.5% (95% CI:
      +0.8%, -5.7%, ns). When data from the two studies were combined the reduction in
      LDL-C by the HG broccoli was significantly greater than standard broccoli (p =
      0.031). CONCLUSION: Evidence from two independent human studies indicates that
      consumption of high glucoraphanin broccoli significantly reduces plasma LDL-C.

PMID- 25851423
TI  - Intraoperative acupuncture for posttonsillectomy pain: a randomized, double
      blind, placebo-controlled trial.
AB  - OBJECTIVES/HYPOTHESIS: To evaluate the effect of intraoperative acupuncture on
      posttonsillectomy pain in the pediatric population. STUDY DESIGN: Prospective,
      double-blind, randomized, placebo-controlled trial. METHODS: Patients aged 3 to
      12 years undergoing tonsillectomy were recruited at a tertiary children's
      hospital between February 2011 and May 2012. Participants were block-randomized
      to receive acupuncture or sham acupuncture during anesthesia for tonsillectomy.
      Surgeons, staff, and parents were blinded from treatment. Tonsillectomy was
      performed by one of two surgeons using a standard technique (monopolar cautery),
      and a single anesthetic protocol was followed. Study endpoints included time
      spent in the postanesthesia care unit, the amount of opioids administered in the
      perioperative period, and pain measures and presence of nausea/vomiting from
      postoperative home surveys. RESULTS: Fifty-nine children aged 3 to 12 years were
      randomized to receive acupuncture (n = 30) or sham acupuncture (n = 29). No
      significant demographic differences were noted between the two cohorts.
      Perioperative data were recorded for all patients; 73% of patients later returned
      home surveys. There were no significant differences in the amount of opioid
      medications administered or total postanesthesia care unit time between the two
      cohorts. Home surveys of patients but not of parents revealed significant
      improvements in pain control in the acupuncture treatment-group postoperatively
      (P = 0.0065 and 0.051, respectively), and oral intake improved significantly
      earlier in the acupuncture treatment group (P = 0.01). No adverse effects of
      acupuncture were reported. CONCLUSIONS: This study demonstrates that
      intraoperative acupuncture is feasible, well tolerated, and results in improved
      pain and earlier return of diet postoperatively. LEVEL OF EVIDENCE: 1b.

PMID- 25851424
TI  - Epidemiology of superficial mycoses in Northern Greece: a 4-year study.
AB  - BACKGROUND: Superficial mycoses are defined as the fungal infections of skin,
      hair or nails that are caused by dermatophytes, yeasts and non-dermatophytic
      moulds. Dermatophytes are the most frequently isolated fungi from specimens of
      patients with superficial mycoses. OBJECTIVE: Studying the possible alteration of
      the epidemiology of superficial mycoses in Northern Greece during the last two to
      three decades. MATERIALS AND METHODS: Data concerning the superficial mycoses
      from patients coming mainly from the region of Macedonia, Northern Greece,
      between January 2010 and January 2014 were recorded and analysed. They included
      specimens from 438 patients (146 M/292 F), within an age range of 2-85 years old.
      503 samples were collected from skin (81, 16.1%), hair (18, 3.6%) and nails
      (fingernails 84, 16.7%, toenails 320, 63.6%) lesions. RESULTS: Of a total of 222
      positive cultures, 50 were considered as yielding clinically non-significant
      isolates (saprophytes). Among the rest (172), dermatophytes were the most
      prevalent isolates (102, 59.3%), followed by yeasts (51, 29.7%) and non
      dermatophytic moulds (19, 11%). Trichophyton rubrum (55, 53.9%), Trichophyton
      mentagrophytes (18, 17.6%) and Microsporum canis (23, 22.5%) were the most common
      isolates among dermatophytes (total = 102). Candida parapsilosis (26, 51%), and
      Candida albicans (10, 19.6%) among yeasts (total = 51) whereas Fusarium (6,
      31.6%) and Acremonium species (3, 15.8%) among the non-dermatophytic moulds
      (total=19). CONCLUSION: Compared to previous studies from Northern Greece, the
      epidemiology of superficial mycoses in the specific geographic region seems not
      to have been altered the last two to three decades.

PMID- 25851425
TI  - Post-meal perceivable satiety and subsequent energy intake with intake of
      partially hydrolysed guar gum.
AB  - Partially hydrolysed guar gum (PHGG), a soluble dietary fibre, has been shown to
      provide many health benefits. Previous studies had suggested that the combination
      of PHGG with protein provided a significant satiation effect on visual analogue
      scales (VAS). What was lacking was only the effect of administration of small
      doses of PHGG on post-meal satiation and subsequent energy intake. The objectives
      of the present investigations were to find the subjective perception of post-meal
      satiety with acute and long term administration of small amounts of PHGG alone
      with food, its effects on subsequent energy intake and the comparative effects
      among different types of soluble fibres. The following three separate studies
      were conducted: in study 1, healthy subjects (n 12) consumed PHGG along with
      breakfast, lunch and an evening snack; in study 2, healthy subjects (n 24)
      consumed 2 g of PHGG or dextrin along with yogurt as breakfast for 2 weeks; in
      study 3, healthy subjects (n 6) took 6 g each of either PHGG or indigestible
      dextrin or inulin along with lunch. In all the studies, various satiety
      parameters were measured on VAS before and after consumption of PHGG. The
      addition of PHGG showed significant (P < 0.05) acute (studies 1 and 3) and long
      term (studies 1 and 2) satiety effects compared to the control and/or an equal
      amount of carbohydrate or other types of soluble fibre. Study 2 also indicated
      that the prolonged consumption of PHGG may significantly (P < 0.05) reduce energy
      intake from whole-day snacking. PHGG could be an ideal natural soluble fibre for
      delivering acute and long term satiety effects for comfortable appetite control.

PMID- 25851426
TI  - Condensed lignin structures and re-localization achieved at high severities in
      autohydrolysis of Eucalyptus globulus wood and their relationship with cellulose
      accessibility.
AB  - Eucalyptus globulus wood was subjected to autohydrolysis pretreatment at
      different severity factors. The pretreated materials were enzymatically
      saccharified at a substrate load of 10% (w/v) using a cellulase enzyme complex.
      Around 82-95% of original glucans were retained in the pretreated material, and
      the enzymatic hydrolysis yields ranged from 58% to 90%. The chemical and
      structural changes in the pretreated materials were investigated by microscopic
      (SEM, LSCM) and spectroscopic (2D-HSQC NMR and FT-IR) techniques. 2D-NMR results
      showed a reduction in the amounts of beta-O-4 aryl-ether linkages and suggested
      the presence of newly condensed structures of lignin in the biomass pretreated at
      the more severe conditions. Furthermore, the microscopic analysis showed that
      lignin migrates out of the cell wall and re-deposits in certain regions of the
      fibers at the more severe conditions to form droplet-like structures and expose
      the cellulose surface. These changes improved the glucose yield up to 69%, on dry
      wood basis.

PMID- 25851427
TI  - Organisational interventions for improving wellbeing and reducing work-related
      stress in teachers.
AB  - BACKGROUND: The teaching profession is an occupation with a high prevalence of
      work-related stress. This may lead to sustained physical and mental health
      problems in teachers. It can also negatively affect the health, wellbeing and
      educational attainment of children, and impose a financial burden on the public
      budget in terms of teacher turnover and sickness absence. Most evaluated
      interventions for the wellbeing of teachers are directed at the individual level,
      and so do not tackle the causes of stress in the workplace. Organisational-level
      interventions are a potential avenue in this regard. OBJECTIVES: To evaluate the
      effectiveness of organisational interventions for improving wellbeing and
      reducing work-related stress in teachers. SEARCH METHODS: We searched the
      Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE,
      PsycINFO, ASSIA, AEI, BEI, BiblioMap, DARE, DER, ERIC, IBSS, SSCI, Sociological
      Abstracts, a number of specialist occupational health databases, and a number of
      trial registers and grey literature sources from the inception of each database
      until January 2015. SELECTION CRITERIA: Randomised controlled trials (RCTs),
      cluster-RCTs, and controlled before-and-after studies of organisational-level
      interventions for the wellbeing of teachers. DATA COLLECTION AND ANALYSIS: We
      used standard methodological procedures expected by Cochrane. MAIN RESULTS: Four
      studies met the inclusion criteria. They were three cluster-randomised controlled
      trials and one with a stepped-wedge design.Changing task characteristicsOne study
      with 961 teachers in eight schools compared a task-based organisational change
      intervention along with stress management training to no intervention. It found a
      small reduction at 12 months in 10 out of 14 of the subscales in the Occupational
      Stress Inventory, with a mean difference (MD) varying from -3.84 to 0.13, and a
      small increase in the Work Ability Index (MD 2.27; 95% confidence interval (CI)
      1.64 to 2.90; 708 participants, low-quality evidence).Changing organisational
      characteristicsTwo studies compared teacher training combined with school-wide
      coaching support to no intervention. One study with 59 teachers in 43 schools
      found no significant effects on job-related anxiety (MD -0.25 95% CI -0.61 to
      0.11, very low-quality evidence) or depression (MD -0.26 95% CI -0.57 to 0.05,
      very low-quality evidence) after 24 months. The other study with 77 teachers in
      18 schools found no significant effects on the Maslach Burnout Inventory
      subscales (e.g. emotional exhaustion subscale: MD -0.05 95% CI -0.52 to 0.42, low
      quality evidence) or the Teacher Perceived Emotional Ability subscales (e.g.
      regulating emotions subscale: MD 0.11 95% CI -0.11 to 0.33, low-quality evidence)
      after six months.Multi-component interventionOne study with 1102 teachers in 34
      schools compared a multi-component intervention containing performance bonus, job
      promotion opportunities and mentoring support to a matched-comparison group
      consisting of 300 schools. It found moderately higher teacher retention rates (MD
      11.50 95% CI 3.25 to 19.75 at 36 months follow-up, very low-quality evidence).
      However, the authors reported results only from one cohort out of four (eight
      schools), demonstrating a high risk of reporting bias. AUTHORS' CONCLUSIONS: We
      found low-quality evidence that organisational interventions lead to improvements
      in teacher wellbeing and retention rates. We need further evaluation of the
      effects of organisational interventions for teacher wellbeing. These studies
      should follow a complex-interventions framework, use a cluster-randomised design
      and have large sample sizes.

PMID- 25851428
TI  - Invited editorial: zoonotic lymphatic filariasis in the Americas: trends in
      epidemiology, diagnosis and treatment, with special emphasis on brugian
      filariasis.

PMID- 25851429
TI  - Human anthrax as a re-emerging disease.
AB  - Anthrax is primarily a disease of herbivores and the etiological agent is B.
      anthracis which is a gram-positive, aerobic, spore-forming, and rod shaped
      bacterium. Bacillus anthracis spores are highly resistant to heat, pressure,
      ultraviolet and ionizing radiation, chemical agents and disinfectants. For these
      reasons, B. anthracis spores are an attractive choice as biological agents for
      the use of bioweapon and/or bioterrorism. Soil is the main reservoir for the
      infectious agent. The disease most commonly affects wild and domestic mammals.
      Human are secondarily infected by contact with infected animals and contaminated
      animal products or directly expose to B. anthracis spores. Anthrax occurs
      worldwide. This infection is still endemic or hyperendemic in both animals and
      humans in some part of areas of the world; particularly in Middle East, West
      Africa, Central Asia, some part of India, South America. However, some countries
      are claiming free of anthrax, and anthrax has become a re-emerging disease in
      western countries with the intentional outbreak. Currently, anthrax is classified
      according to its setting as (1) naturally occurring anthrax, (2) bioterrorism
      related anthrax. Vast majority of human anthrax are occurring as naturally
      occurring anthrax in the world. It is also a threaten disease for western
      countries. The aim of this paper is to review the relevant patents, short
      historical perspective, microbiological and epidemiological features, clinical
      presentations and treatment. 

PMID- 25851430
TI  - Brucellosis and its particularities in children travelers.
AB  - Brucellosis is still endemic in many countries in the world, however, having a
      significantly higher incidence in developing countries. As consequence of travel,
      risk for children from non-endemic areas would be considerable when visiting
      developing countries. Then, the purpose of this review is to provide, after a
      bibliographical search, an update on the main aspects of this disease in the
      traveler children. For the general practitioner, but particularly for travel
      medicine practitioner and pediatricians, these clinicoepidemiological
      considerations should be taken in mind in the differential diagnosis when
      assessing children returning from travel to brucellosis endemic areas. 

PMID- 25851431
TI  - Shape-tailored colloidal molecules obtained by self-assembly of model gold
      nanoparticles with flexible polyelectrolyte.
AB  - We study for the first time the structure of stable finite size clusters (i.e.,
      colloidal molecules) obtained by self-assembly of cationic gold nanoparticles
      (i.e., atoms) mediated by a flexible polyanion. We reveal with nondenaturizing
      techniques a striking structural transition from 1D small chains of 12 gold
      nanoparticles (AuNPs) with a self-avoiding conformation to 3D fractal clusters of
      130 AuNPs with short-range ordering around the charge inversion threshold.
      Interestingly, these well-defined structures are obtained by simple mixing in
      water without anisotropic functionalization or external forces. As a preliminary
      step, we introduce a new synthesis pathway leading to well-defined cationic AuNPs
      of controllable size that can be dispersed in H2O or D2O without aggregation and
      ligands' self-assemblies. On this occasion, we point for the first time that
      usual procedures do not enable to eliminate cationic ligands' self-assemblies
      that could play an undesired role in AuNPs' self-assembly through electrostatic
      interactions. 

PMID- 25851432
TI  - Prostatic arterial embolization for the treatment of lower urinary tract symptoms
      caused by benign prostatic hyperplasia: a comparative study of medium- and large
      volume prostates.
AB  - OBJECTIVES: To compare the outcomes of prostatic arterial embolization (PAE) in
      treating large (>80 mL) in comparison with medium-sized prostate glands (50-80
      mL) to determine whether size affects the outcome of PAE. PATIENTS AND METHODS: A
      total of 115 patients (mean age 71.5 years) diagnosed with lower urinary tract
      symptoms (LUTS) attributable to benign prostatic hyperplasia (BPH) refractory to
      medical treatment underwent PAE. Group A (n = 64) included patients with a mean
      prostate volume of 129 mL; group B (n = 51) included patients with a mean
      prostate volume of 64 mL. PAE was performed using 100-MUm particles. Follow-up
      was performed using the International Prostate Symptom Score (IPSS), quality of
      life (QoL), peak urinary flow rate (Qmax ), post-void residual urine volume
      (PVR), the International Index of Erectile Function short form (IIEF-5), prostate
      specific antigen (PSA) and prostate volume measured by magnetic resonance imaging
      at 1, 3 and 6 months, and every 6 months thereafter. RESULTS: There were no
      significant differences between groups in baseline IPSS, QoL, Qmax , PVR, PSA
      level or IIEF-5 score. The technical success rate was 93.8% in group A and 96.8%
      in group B (P = 0.7). A total of 101 patients (55 patients in group A and 46
      patients in group B) completed the mean (range) follow-up of 17 (12-33) months.
      Compared with baseline, there were significant improvements in IPSS, QoL, Qmax ,
      prostate volume and PVR in both groups after PAE. The outcomes in group A were
      significantly better than in group B with regard to mean +/- sd IPSS (-14 +/- 6.5
      vs -10.5 +/- 5.5, respectively), Qmax (6.0 +/- 1.5 vs 4.5 +/- 1.0 mL/s,
      respectively), PVR (-80.0 +/- 25.0 vs -60.0 +/- 20.0 mL, respectively), prostate
      volume (-54.5 +/- 18.0 mL [-42.3%] vs -18.5 +/- 5.0 mL [-28.9%], respectively),
      and QoL score (-3.0 +/- 1.5 vs -2.0 +/- 1.0) with P values <0.05. The mean IIEF-5
      score was not significantly different from baseline in both groups. No major
      complications were noted. CONCLUSIONS: We found that PAE is a safe and effective
      treatment method for patients with LUTS attributable to BPH. The clinical and
      imaging outcomes of PAE were better in patients with larger prostate glands than
      medium-sized ones.

PMID- 25851434
TI  - Richard Dronskowski.
AB  - "My "science heroes" are Otto Hahn and Hans Hellmann. My favorite authors are
      Walter Kempowski and John Updike ...?" This and more about Richard Dronskowski
      can be found on page 8872. 

PMID- 25851433
TI  - Treatment of peri-implant mucositis using a glycine powder air-polishing or
      ultrasonic device: a randomized clinical trial.
AB  - AIM: To evaluate the clinical treatment effects of a glycine powder air-polishing
      or ultrasonic device on peri-implant mucositis. MATERIALS AND METHODS: Thirty
      seven patients with one implant diagnosed with peri-implant mucositis (probing
      depth >=4 mm (0.2N) and bleeding on probing (BOP) (primary outcome)) were
      randomly assigned to treatment with either glycine powder air-polishing (GPAP) or
      ultrasonic (US) debridement. Treatment was performed at baseline and at 3 and 6
      months. Professional supra gingival cleaning was performed at 9 and 12 months.
      Oral hygiene instructions were reinforced at each visit. RESULTS: At 12 months
      there was a statistically significant reduction in mean plaque score, bleeding on
      probing and number of periodontal pockets >=4 mm within the treatment groups
      compared to baseline. The percentages of diseased sites were significantly
      reduced for both groups. CONCLUSIONS: Treatment with a glycine powder air
      polishing or an ultrasonic device is effective in non-surgical treatment of peri
      implant mucositis.

PMID- 25851435
TI  - Sleep disordered breathing in patients with Prader-Willi syndrome: A multicenter
      study.
AB  - OBJECTIVES: Sleep disordered breathing (SDB) is common in patients with Prader
      Willi syndrome (PWS) and systematic screening is recommended, especially before
      growth hormone treatment. The aim of the study was to describe the baseline SDB
      and therapeutic interventions in a large cohort of patients. STUDY DESIGN:
      Retrospective study. SUBJECT SELECTION: Eighty-eight patients with PWS, median
      [interquartile range] age of 5.1 [1.0-14.5] years old (range 0.3-44.3), who were
      followed in three centers (France, Italy). METHODOLOGY: Anthropometrics,
      polygraphy (PG), and gas exchange data were analyzed. RESULTS: Median body mass
      index (BMI) was 20 [16-34] kg/m(2), BMI z-score for patients aged 2-20 years old
      was 2.1 [1.2-2.8] SD, mixed-obstructive apnea-hypopnea index (MOAHI) 1.8 [0.6
      5.0] events/hr, and central apnea index (CAI) 0.1 [0.0-0.6] events/hr. Minimum
      pulse oximetry (SpO2) was 88 [84-91]%, percentage of time with SpO2 <90% 0.1 [0.0
      1.0]%, and oxygen desaturation index 2 [1-4]/hr. An apnea-hypopnea index (AHI) >=
      1.5 and >= 5 events/hr was observed in 53% of children and 41% of adults,
      respectively. No correlations were observed between MOAHI and anthropometrics
      data (age, BMI, BMI z-score), while MOAHI significantly correlated with SpO2
      indexes. Age and BMI only weakly correlated with SpO2 indexes. Growth hormone
      could be initiated in 48 patients. Regarding post-PG therapy, 9 patients had
      upper airway surgery, and noninvasive CPAP/bilevel ventilation was started in 16
      patients. CONCLUSIONS: Patients with PWS exhibit a high prevalence of SDB. The
      lack of association between obesity and SDB leads to hypothesize that hypotonia
      and/or facial dysmorphic features may play a major role in the occurrence of SDB.

PMID- 25851437
TI  - Menstrual cycle, sex hormones in female inflammatory bowel disease patients with
      and without surgery.
AB  - Healthy women at reproductive age experience a cyclical alteration of
      gastrointestinal (GI) symptomatology during their menstrual cycle. Additionally,
      the majority of healthy women also complain of worsening of GI symptoms either
      during the premenstrual or menstrual phase. Despite conflicting evidence, studies
      suggest that sex hormones may increase GI transit time during the luteal phase.
      Similar phenomenon is also observed in women with underlying inflammatory bowel
      disease (IBD). The mechanism underlying this complex pathophysiology is still not
      completely understood. However, a possible influence of sex hormones on the brain
      gut-microbiota axis is hypothesized. The diagnosis of IBD is associated with a
      delay in menarche as well as menstrual function irregularities including
      alterations in cycle length and the duration of flow. There is little data on the
      effect of menopause on IBD disease activity and conflicting data on the effect of
      IBD diagnosis on the onset of menopause. The role of contraceptives and hormone
      replacement therapies on the development or disease activity of IBD has not been
      yet established. Moreover, IBD patients with concomitant dysmenorrhea report
      heightened pain during menses. The effect of non-steroidal anti-inflammatory
      drugs in treating primary dysmenorrhea on the disease course of IBD is unknown.
      In addition, the effect of IBD medications including immunomodulators and
      biologics on menstrual function remains unclear. Also, the role of IBD surgery on
      menstrual irregularities needs to be fully elucidated. Hence, understanding the
      influence of menstrual function on IBD disease activity and vice versa and the
      maintenance of normal menstrual function in those patients is important in
      improving overall reproductive health and fertility and outcome of IBD. 

PMID- 25851436
TI  - Deformability in the cleavage site of primary microRNA is not sensed by the
      double-stranded RNA binding domains in the microprocessor component DGCR8.
AB  - The prevalence of double-stranded RNA (dsRNA) in eukaryotic cells has only
      recently been appreciated. Of interest here, RNA silencing begins with dsRNA
      substrates that are bound by the dsRNA-binding domains (dsRBDs) of their
      processing proteins. Specifically, processing of microRNA (miRNA) in the nucleus
      minimally requires the enzyme Drosha and its dsRBD-containing cofactor protein,
      DGCR8. The smallest recombinant construct of DGCR8 that is sufficient for in
      vitro dsRNA binding, referred to as DGCR8-Core, consists of its two dsRBDs and a
      C-terminal tail. As dsRBDs rarely recognize the nucleotide sequence of dsRNA, it
      is reasonable to hypothesize that DGCR8 function is dependent on the recognition
      of specific structural features in the miRNA precursor. Previously, we
      demonstrated that noncanonical structural elements that promote RNA flexibility
      within the stem of miRNA precursors are necessary for efficient in vitro cleavage
      by reconstituted Microprocessor complexes. Here, we combine gel shift assays with
      in vitro processing assays to demonstrate that neither the N-terminal dsRBD of
      DGCR8 in isolation nor the DGCR8-Core construct is sensitive to the presence of
      noncanonical structural elements within the stem of miRNA precursors, or to
      single-stranded segments flanking the stem. Extending DGCR8-Core to include an N
      terminal heme-binding region does not change our conclusions. Thus, our data
      suggest that although the DGCR8-Core region is necessary for dsRNA binding and
      recruitment to the Microprocessor, it is not sufficient to establish the
      previously observed connection between RNA flexibility and processing efficiency.

PMID- 25851438
TI  - Model-based standardization to adjust for unmeasured cluster-level confounders
      with complex survey data.
AB  - Model-based standardization uses a statistical model to estimate a standardized,
      or unconfounded, population-averaged effect. With it, one can compare groups had
      the distribution of confounders been identical in both groups to that of the
      standard population. We develop two methods for model-based standardization with
      complex survey data that accommodate a categorical confounder that clusters the
      individual observations into a very large number of subgroups. The first method
      combines a random-intercept generalized linear mixed model with a conditional
      pseudo-likelihood estimator of the fixed effects. The second method combines a
      between-within generalized linear mixed model with census data on the cluster
      level means of the individual-level covariates. We conduct simulation studies to
      compare the two approaches. We apply the two methods to the 2008 Florida
      Behavioral Risk Factor Surveillance System survey data to estimate standardized
      proportions of people who drink alcohol, within age groups, adjusting for
      measured individual-level and unmeasured cluster-level confounders.

PMID- 25851439
TI  - Investigation of the use of aerobic granules for the treatment of sugar beet
      processing wastewater.
AB  - The treatment of sugar beet processing wastewater in aerobic granular sequencing
      batch reactor (SBR) was examined in terms of chemical oxygen demand (COD) and
      nitrogen removal efficiency. The effect of sugar beet processing wastewater of
      high solid content, namely 2255 +/- 250 mg/L total suspended solids (TSS), on
      granular sludge was also investigated. Aerobic granular SBR initially operated
      with the effluent of anaerobic digester treating sugar beet processing wastewater
      (Part I) achieved average removal efficiencies of 71 +/- 30% total COD (tCOD), 90
      +/- 3% total ammonifiable nitrogen (TAN), 76 +/- 24% soluble COD (sCOD) and 29 +/
      4% of TSS. SBR was further operated with sugar beet processing wastewater (Part
      II), where the tCOD, TAN, sCOD and TSS removal efficiencies were 65 +/- 5%, 61 +/
      4%, 87 +/- 1% and 58 +/- 10%, respectively. This study indicated the
      applicability of aerobic granular SBRs for the treatment of both sugar beet
      processing wastewater and anaerobically digested processing wastewater. For
      higher solids removal, further treatment such as a sedimentation tank is required
      following the aerobic granular systems treating solid-rich wastewaters such as
      sugar beet processing wastewater. It was also revealed that the application of
      raw sugar beet processing wastewater slightly changed the aerobic granular sludge
      properties such as size, structure, colour, settleability and extracellular
      polymeric substance content, without any drastic and negative effect on treatment
      performance.

PMID- 25851440
TI  - A common case with common problems: laparoscopic treatment of small bowel
      obstruction (SBO).
AB  - BACKGROUND: Laparoscopic approach to patients with suspected small bowel
      obstruction (SBO) is not yet widely accepted nor clearly standardized; due to the
      absence of randomized trials, many questions still remain matter of debate.
      METHODS: By describing a single typical case of acute intestinal occlusive
      syndrome in a 82 years old woman, in which a SBO was suspected on the basis of
      previous surgical history and CT scan imaging, every single step of therapy is
      discussed, including the decision to perform explorative laparoscopy, the first
      trocar placement, the decision to continue by laparoscopy or to convert in
      laparotomy, and finally the small bowel resection and re-anastomosis. RESULTS:
      The decision to approach a suspected SBO by laparoscopy should be taken on the
      basis of a number of features which would predict the success rate, such as mild
      abdominal distention, proximal obstruction, partial obstruction, small bowel
      diameter less than 4 cm, previous appendenctomy, anticipated single band
      adhesion. In these cases laparoscopic approach may improve post-operative
      outcomes in terms of reduced postoperative ileus, hospitalization and wound
      infection rate. CONCLUSIONS: In selected, not unusual cases of SBO, a
      laparoscopic approach is feasible and effective. A growing Literature, mainly
      based upon retrospective series, is available. KEY WORDS: Conversion,
      Laparoscopy, Mortality, Small bowel obstruction, Surgery.

PMID- 25851441
TI  - Tight junction disruption by cadmium in an in vitro human airway tissue model.
AB  - BACKGROUND: The cadmium (Cd) present in air pollutants and cigarette smoke has
      the potential of causing multiple adverse health outcomes involving damage to
      pulmonary and cardiovascular tissue. Injury to pulmonary epithelium may include
      alterations in tight junction (TJ) integrity, resulting in impaired epithelial
      barrier function and enhanced penetration of chemicals and biomolecules. Herein,
      we investigated mechanisms involved in the disruption of TJ integrity by Cd
      exposure using an in vitro human air-liquid-interface (ALI) airway tissue model
      derived from normal primary human bronchial epithelial cells. METHODS: ALI
      cultures were exposed to noncytotoxic doses of CdCl2 basolaterally and TJ
      integrity was measured by Trans-Epithelial Electrical Resistance (TEER) and
      immunofluorescence staining with TJ markers. PCR array analysis was used to
      identify genes involved with TJ collapse. To explore the involvement of kinase
      signaling pathways, cultures were treated with CdCl2 in the presence of kinase
      inhibitors specific for cellular Src or Protein Kinase C (PKC). RESULTS:
      Noncytotoxic doses of CdCl2 resulted in the collapse of barrier function, as
      demonstrated by TEER measurements and Zonula occludens-1 (ZO-1) and occludin
      staining. CdCl2 exposure altered the expression of several groups of genes
      encoding proteins involved in TJ homeostasis. In particular, down-regulation of
      select junction-interacting proteins suggested that a possible mechanism for Cd
      toxicity involves disruption of the peripheral junctional complexes implicated in
      connecting membrane-bound TJ components to the actin cytoskeleton. Inhibition of
      kinase signaling using inhibitors specific for cellular Src or PKC preserved the
      integrity of TJs, possibly by preventing occludin tyrosine hyperphosphorylation,
      rather than reversing the down-regulation of the junction-interacting proteins.
      CONCLUSIONS: Our findings indicate that acute doses of Cd likely disrupt TJ
      integrity in human ALI airway cultures both through occludin hyperphosphorylation
      via kinase activation and by direct disruption of the junction-interacting
      complex.

PMID- 25851442
TI  - Tillage Management and Seasonal Effects on Denitrifier Community Abundance, Gene
      Expression and Structure over Winter.
AB  - Tillage effects on denitrifier communities and nitrous oxide (N2O) emissions were
      mainly studied during the growing season. There is limited information for the
      non-growing season, especially in northern countries where winter has prolonged
      periods with sub-zero temperatures. The abundance and structure of the
      denitrifier community, denitrification gene expression and N2O emissions in
      fields under long-term tillage regimes [no-tillage (NT) vs conventional tillage
      (CT)] were assessed during two consecutive winters. NT exerted a positive effect
      on nirK and nosZ denitrifier abundance in both winters compared to CT. Moreover,
      the two contrasting managements had an opposite influence on nirK and nirS
      RNA/DNA ratios. Tillage management resulted in different denitrifier community
      structures during both winters. Seasonal changes were observed in the abundance
      and the structure of denitrifiers. Interestingly, the RNA/DNA ratios were greater
      in the coldest months for nirK, nirS and nosZ. N2O emissions were not influenced
      by management but changed over time with two orders of magnitude increase in the
      coldest month of both winters. In winter of 2009-2010, emissions were mainly as
      N2O, whereas in 2010-2011, when soil temperatures were milder due to persistent
      snow cover, most emissions were as dinitrogen. Results indicated that tillage
      management during the growing season induced differences in denitrifier community
      structure that persisted during winter. However, management did not affect the
      active cold-adapted community structure. 

PMID- 25851443
TI  - Picophytoplankton as Tracers of Environmental Forcing in a Tropical Monsoonal
      Bay.
AB  - In order to better understand the picophytoplankton (PP) dynamics in tropical
      monsoon influenced coastal regions, samples were collected daily (June-September
      2008: monsoon, December 2008: post-monsoon and April 2009: pre-monsoon) from a
      fixed station in Dona Paula Bay, India. Eight PP abundance peaks comprising
      Prochlorococcus-like cells, picoeukaryotes, and three groups of Synechococcus
      occurred. The chlorophyll biomass and PP abundance were negatively influenced by
      reduced solar radiation, salinity and water transparency due to precipitation and
      positively influenced by the stabilized waters during precipitation break/non
      monsoon periods. Responses to environmental conditions differed with PP groups,
      wherein the presence of Synechococcus-PEI (phycoerythrin) throughout the year
      suggested its ability to tolerate salinity and temperature variations and low
      light conditions. Synechococcus-PEII appearance toward monsoon end and non
      monsoon during high water transparency suggests its tidal advection from offshore
      waters. Dominance of Synechococcus-PC (phycocyanin) at intermediate salinities
      under low water transparency during MON and high salinities in PrM coinciding
      with high nitrate concentrations implies a greater influence of light quality or
      nutrients. Cyanobacteria and not picoeukaryotes were the dominant
      picophytoplankton in terms of numbers as well as biomass. This study suggests
      that PP could be used as tracers of environmental forcing driven by tides and
      freshwater influx and also highlights the importance of high-frequency samplings
      in dynamic coastal regions through which transient responses can be captured. 

PMID- 25851444
TI  - Diversity and Ecological Characterization of Sporulating Higher Filamentous
      Marine Fungi Associated with Spartina maritima (Curtis) Fernald in Two Portuguese
      Salt Marshes.
AB  - Fungal communities associated with early stages of decomposition of Spartina
      maritima (Curtis) Fernald were assessed in two geographically distinct salt
      marshes in Portugal by direct observation of fungal sporulating structures.
      Twenty-three fungal taxa were identified from 390 plant samples, 11 of which were
      common to both study sites. Natantispora retorquens, Byssothecium obiones,
      Phaeosphaeria spartinicola, Phoma sp. 1 and Stagonospora sp. were the most
      frequent fungal taxa in the studied communities. The fungal species Anthostomella
      spissitecta, Camarosporium roumeguerii, Coniothyrium obiones, Decorospora
      gaudefroyi, Halosarpheia trullifera, Leptosphaeria marina and Stagonospora
      haliclysta were recorded for the first time on S. maritima plants; with the
      exception of C. roumeguerii and L. marina, all of these species were also new
      records for Portugal. The differences between species composition of the
      communities associated with S. maritima were attributed to differences in abiotic
      conditions of the salt marshes. Although the fungal taxa were distributed
      differently along the host plants, common species to both fungal communities were
      found on the same relative position, e.g. B. obiones, Lulworthia sp. and N.
      retorquens occurred on the basal plant portions, Buergenerula spartinae,
      Dictyosporium pelagicum and Phoma sp. 1 on the middle plant portions and P.
      spartinicola and Stagonospora sp. on the top plant portions. The distinct
      vertical distribution patterns reflected species-specific salinity requirements
      and flooding tolerance, but specially substrate preferences. The most frequent
      fungi in both communities also exhibited wider distribution ranges and produced a
      higher number of fruiting structures, suggesting a more active key role in the
      decay process of S. maritima. 

PMID- 25851445
TI  - Temporal Dynamics of Active Prokaryotic Nitrifiers and Archaeal Communities from
      River to Sea.
AB  - To test if different niches for potential nitrifiers exist in estuarine systems,
      we assessed by pyrosequencing the diversity of archaeal gene transcript markers
      for taxonomy (16S ribosomal RNA (rRNA)) during an entire year along a salinity
      gradient in surface waters of the Charente estuary (Atlantic coast, France). We
      further investigated the potential for estuarine prokaryotes to oxidize ammonia
      and hydrolyze urea by quantifying thaumarchaeal amoA and ureC and bacterial amoA
      transcripts. Our results showed a succession of different nitrifiers from river
      to sea with bacterial amoA transcripts dominating in the freshwater station while
      archaeal transcripts were predominant in the marine station. The 16S rRNA
      sequence analysis revealed that Thaumarchaeota marine group I (MGI) were the most
      abundant overall but other archaeal groups like Methanosaeta were also
      potentially active in winter (December-March) and Euryarchaeota marine group II
      (MGII) were dominant in seawater in summer (April-August). Each station also
      contained different Thaumarchaeota MGI phylogenetic clusters, and the clusters'
      microdiversity was associated to specific environmental conditions suggesting the
      presence of ecotypes adapted to distinct ecological niches. The amoA and ureC
      transcript dynamics further indicated that some of the Thaumarchaeota MGI
      subclusters were involved in ammonia oxidation through the hydrolysis of urea.
      Our findings show that ammonia-oxidizing Archaea and Bacteria were adapted to
      contrasted conditions and that the Thaumarchaeota MGI diversity probably
      corresponds to distinct metabolisms or life strategies. 

PMID- 25851446
TI  - Changes in the Synechococcus Assemblage Composition at the Surface of the East
      China Sea Due to Flooding of the Changjiang River.
AB  - The aim of this study was to elucidate how flooding of the Changjiang River
      affects the assemblage composition of phycoerythrin-rich (PE-rich) Synechococcus
      at the surface of the East China Sea (ECS). During non-flooding summers (e.g.,
      2009), PE-rich Synechococcus usually thrive at the outer edge of the Changjiang
      River diluted water coverage (CDW; salinity <=31 PSU). In the summer of 2010, a
      severe flood occurred in the Changjiang River basin. The plentiful freshwater
      injection resulted in the expansion of the CDW over half of the ECS and caused PE
      rich cells to show a uniform distribution pattern, with decreased abundance
      compared with the non-flooding summer. The phylogenetic diversity of 16S rRNA
      gene sequences indicated that the flooding event also shifted the picoplankton
      community composition from being dominated by Synechococcus, mainly attributed to
      the clade II lineage, to various orders of heterotrophic bacteria, including
      Actinobacteria, Flavobacteria, alpha-Proteobacteria, and gamma-Proteobacteria. As
      an increasing number of studies have proposed that global warming might result in
      more frequent floods, combining this perspective with the information obtained
      from our previous [1] and this studies yield a more comprehensive understanding
      of the relationship between the composition of the marine Synechococcus
      assemblage and global environmental changes. 

PMID- 25851447
TI  - A cutaneous lesion.

PMID- 25851448
TI  - Antiphospholipid syndrome: an update.
AB  - BACKGROUND: Antiphospholipid syndrome (APS) or 'Hughes syndrome' is a
      prothrombotic disease characterized by thrombosis and pregnancy morbidity in the
      presence of antiphospholipid antibodies (aPL). More than three decades have
      passed, and experts are still uncovering new pieces of this disease complex
      pathogenesis and management. MATERIALS AND METHODS: We searched in literature
      using MEDLINE and PubMed databases focusing on the latest development on disease
      pathogenesis, risk assessment of thrombosis and treatment of APS. RESULTS: The
      phosphatidylinositol 3-kinase (PI3K)-AKT-mTORC pathway was most recently
      identified to have a crucial role in activating inflammation among endothelial
      vessel wall causing vascular lesions in APS. Additionally, new variables are
      being implemented to assess the risk of thrombosis in patients with APS. Global
      APS Score (GAPSS) utilizes cardiovascular risk factors and new autoimmune
      antibodies as part of the score assessment and is the most valid so far. It can
      be a promising tool in the future for prediction of thrombosis. Anticoagulation
      remains the cornerstone in APS; however, many new potential therapeutic agents
      are developing and are currently under investigation. CONCLUSIONS: The most
      recent advances in pathogenesis, risk stratification and treatment provide a
      platform for high yield studies with the ultimate goal of providing the optimal
      management to patients with APS.

PMID- 25851449
TI  - Trajectories of relationship stress and inflammatory processes in adolescence.
AB  - Researchers have identified cross-sectional links between interpersonal stress
      and inflammation. Little is known, however, about how these dynamics unfold over
      time, what underlying immune pathways might exist, or whether moderators such as
      race could alter the strength of the connection between interpersonal stress and
      inflammatory processes. We examined whether adolescent girls whose relationship
      trajectories were characterized by chronic stress would exhibit a proinflammatory
      phenotype marked by systemic inflammation, heightened cytokine responses to
      bacterial challenges, and resistance to the anti-inflammatory properties of
      cortisol. Significant Stress * Race interactions revealed that family stress
      trajectories predicted glucocorticoid sensitivity and peer stress trajectories
      predicted cytokine production for White but not Asian girls. Relationship stress
      trajectories were not associated with systemic inflammation, however. These
      findings suggest that particular subgroups of adolescent girls who face chronic
      and elevated stress in their close relationships may be at risk for disruptions
      to the immune system. 

PMID- 25851450
TI  - Reconstruction of the Traumatized Thumb.

PMID- 25851452
TI  - Vertical augmentation/mastopexy: "surgeon, embrace".

PMID- 25851453
TI  - Use of a urea, arginine and carnosine cream versus a standard emollient glycerol
      cream for treatment of severe xerosis of the feet in patients with type 2
      diabetes: a randomized, 8 month, assessor-blinded, controlled trial.
AB  - BACKGROUND: No long-term data are available regarding the effects of emollients
      in treating severe foot skin xerosis in patients with diabetes. STUDY AIM: We
      evaluated the efficacy of 8 month urea, arginine and carnosine cream (UC) in
      comparison with a glycerin-based emollient cream (SEC) in type 2 patients with
      diabetes who had severe foot xerosis. SUBJECTS AND METHODS: We assessed the
      effect of UC and SEC on skin hydration in a randomized, assessor-blinded study in
      50 patients treated with UC (N = 25) or SEC (N = 25) for 32 weeks with a twice
      daily application. Primary outcomes were a 9 point Xerosis Assessment Scale (XAS)
      score and a 4 point Overall Cutaneous Score (OCS), evaluated at baseline and
      after 4, 12 and 32 weeks. Skin hydration and desquamation were also objectively
      evaluated by means of a bio-impedance skin analysis device (Hydr8 * ) at baseline
      and at week 32. RESULTS: UC induced greater hydration than SEC (p = 0.001) with a
      91% reduction at week 32 in XAS score vs. baseline. After 4 weeks, compared with
      the SEC treated group, the XAS score in the UC treated group was significantly
      lower. OCS was reduced by 27% from baseline to end of the study in the UC group,
      and increased by 8% in the SEC group (p = 0.02; between groups). At month 8, skin
      hydration and desquamation evaluated by the digital skin analysis system
      statistically improved in UC treated subjects in comparison with baseline and SEC
      group values. This study was not double-blind. In order to overcome this problem
      we performed an assessor-blinded evaluation of the primary endpoints and used an
      objective measurement tool for skin hydration and desquamation assessment.
      CONCLUSION: Using a urea, arginine and carnosine cream for 8 months increases
      skin hydration and improves skin dryness in type 2 diabetic patients in
      comparison with a glycerol-based emollient cream, with a greater efficacy
      observed as early as 4 weeks into treatment.

PMID- 25851454
TI  - Consent forms for "no surgery" as ramification of landmark ruling.

PMID- 25851455
TI  - Sodium MRI of multiple sclerosis.
AB  - Multiple sclerosis (MS) is the most common cause of non-traumatic disability in
      young adults. The mechanisms underlying neurodegeneration and disease progression
      are poorly understood, in part as a result of the lack of non-invasive methods to
      measure and monitor neurodegeneration in vivo. Sodium MRI is a topic of
      increasing interest in MS research as it allows the metabolic characterization of
      brain tissue in vivo, and integration with the structural information provided by
      (1)H MRI, helping in the exploration of pathogenetic mechanisms and possibly
      offering insights into disease progression and monitoring of treatment outcomes.
      We present an up-to-date review of the sodium MRI application in MS organized
      into four main sections: (i) biological and pathogenetic role of sodium; (ii)
      brief overview of sodium imaging techniques; (iii) results of sodium MRI
      application in clinical studies; and (iv) future perspectives.

PMID- 25851456
TI  - Utility of the QT interval in predicting outcomes in patients presenting to the
      emergency department with chest pain.
AB  - OBJECTIVES: The aim of this study was to investigate whether prolongation of the
      heart rate-corrected QT interval (QTc) is an independent risk factor for
      predicting future acute coronary syndrome (ACS) occurrence or mortality in
      patients with at least one cardiac risk factor presenting with chest pain to the
      emergency department (ED). METHODS: This is a single-center, retrospective study
      of patients presenting with chest pain to the ED of Einstein Medical Center,
      Philadelphia, between 2011 and 2012. Proportional hazards models were used to
      calculate hazard ratios (HRs) for occurrence of ACS or death within 1 year.
      Kaplan-Meier curves were used to determine the time to event for QTc low (< 460
      ms) versus QTc high (>= 460 ms) groups. RESULTS: A total of 595 patients met the
      inclusion criteria. Older age, hypertension, diabetes mellitus, and
      hyperlipidemia were more common in the QTc high group. Patients in the QTc high
      group were more likely to experience subsequent ACS or death (HR 8.12, 95%
      confidence interval 4.00-16.72), even after adjusting for traditional cardiac
      risk factors (HR 7.68, 95% confidence interval 3.57-16.61). CONCLUSION: QTc
      prolongation at ED presentation with chest pain and at least one cardiac risk
      factor predicts subsequent ACS and death.

PMID- 25851458
TI  - Chronic widespread pain: clinical comorbidities and psychological correlates.
AB  - Recent studies have provided consistent evidence for a genetic influence on
      chronic widespread pain (CWP). The aim of this study was to investigate (1) the
      etiological structure underlying CWP by examining the covariation between CWP and
      psychological comorbidities and psychoaffective correlates and (2) the
      decomposition of the covariation into genetic and environmental components. A
      total of 3266 female twins (mean age 56.6 years) were subject to multivariate
      analyses. Using validated questionnaires to classify twins as having CWP, the
      prevalence of CWP was 20.8%. In the multivariate analysis, the most suitable
      model was the common pathway model. This model revealed 2 underlying latent
      variables, one common to anxiety, emotional intelligence, and emotional
      instability (f1) and the other common to depression and CWP (f2), the latter
      being highly heritable (86%). Both latent variables (f1 and f2) shared an
      additive genetic and a nonshared environmental factor. In addition, a second
      additive genetic factor loading only on f2 was found. This study reveals the
      structure of genetic and environmental influences of CWP and its psychoaffective
      correlates. The results show that the clustering of CWP and depression is due to
      a common, highly heritable, underlying latent trait. In addition, we found
      evidence that CWP, anxiety, emotional instability, and emotional intelligence are
      influenced by different underlying latent traits sharing the same genetic and
      nonshared environmental factors. This is the first study to reveal the structure
      and relative importance of genetic and environmental influences on complex
      etiological mechanisms of CWP and its correlates. 

PMID- 25851457
TI  - Chronic constriction injury-induced nociception is relieved by nanomedicine
      mediated decrease of rat hippocampal tumor necrosis factor.
AB  - Neuropathic pain is a chronic pain syndrome that arises from nerve injury.
      Current treatments only offer limited relief, clearly indicating the need for
      more effective therapeutic strategies. Previously, we demonstrated that
      proinflammatory tumor necrosis factor-alpha (TNF) is a key mediator of
      neuropathic pain pathogenesis; TNF is elevated at sites of neuronal injury, in
      the spinal cord, and supraspinally during the initial development of pain. The
      inhibition of TNF action along pain pathways outside higher brain centers results
      in transient decreases in pain perception. The objective of this study was to
      determine whether specific blockade of TNF in the hippocampus, a site of pain
      integration, could prove efficacious in reducing sciatic nerve chronic
      constriction injury (CCI)-induced pain behavior. Small inhibitory RNA directed
      against TNF mRNA was complexed to gold nanorods (GNR-TNF siRNA; TNF nanoplexes)
      and injected into the contralateral hippocampus of rats 4 days after unilateral
      CCI. Withdrawal latencies to a noxious thermal stimulus (hyperalgesia) and
      withdrawal to innocuous forces (allodynia) were recorded up to 10 days and
      compared with baseline values and sham-operated rats. Thermal hyperalgesia was
      dramatically decreased in CCI rats receiving hippocampal TNF nanoplexes; and
      mechanical allodynia was transiently relieved. TNF levels (bioactive protein, TNF
      immunoreactivity) in hippocampal tissue were decreased. The observation that TNF
      nanoplex injection into the hippocampus alleviated neuropathic pain-like behavior
      advances our previous findings that hippocampal TNF levels modulate pain
      perception. These data provide evidence that targeting TNF in the brain using
      nanoparticle-protected siRNA may be an effective strategy for treatment of
      neuropathic pain. 

PMID- 25851459
TI  - Well, I wouldn't start from here.

PMID- 25851460
TI  - Cerebral analgesic response to nonsteroidal anti-inflammatory drug ibuprofen.
AB  - Nonopioid agents, such as nonsteroidal anti-inflammatory drugs (NSAIDs), are the
      most commonly used class of analgesics. Increasing evidence suggests that
      cyclooxygenase (COX) inhibition at both peripheral and central sites can
      contribute to the antihyperalgesic effects of NSAIDs, with the predominant
      clinical effect being mediated centrally. In this study, we examined the cerebral
      response to ibuprofen in presurgical and postsurgical states and looked at the
      analgesic interaction between surgical state and treatment. We used an
      established clinical pain model involving third molar extraction, and
      quantitative arterial spin labelling (ASL) imaging to measure changes in
      tonic/ongoing neural activity. Concurrent to the ASL scans, we presented visual
      analogue scales inside the scanner to evaluate the subjective experience of pain.
      This novel methodology was incorporated into a randomized double-blind placebo
      controlled design, with an open method of drug administration. We found that
      independent of its antinociceptive action, ibuprofen has no effect on regional
      cerebral blood flow under pain-free conditions (presurgery). However, in the
      postsurgical state, we observed increased activation of top-down modulatory
      circuits, which was accompanied by decreases in the areas engaged because of
      ongoing pain. Our findings demonstrate that ibuprofen has a measurable analgesic
      response in the human brain, with the subjective effects of pain relief reflected
      in two distinct brain networks. The observed activation of descending modulatory
      circuits warrants further investigation, as this may provide new insights into
      the inhibitory mechanisms of analgesia that might be exploited to improve safety
      and efficacy in pain management. 

PMID- 25851461
TI  - Destructive Spondyloarthropathy in Patients on Long-Term Peritoneal Dialysis or
      Hemodialysis.
AB  - Destructive spondyloarthropathy (DSA) is the most serious spinal complication of
      dialysis-related amyloidosis in patients on long-term hemodialysis (HD), but we
      could not find any information about DSA in patients on peritoneal dialysis (PD)
      for over 10 years. We retrospectively evaluated factors contributing to DSA in HD
      and PD patients. Sixty-seven patients on dialysis for 10 to 19 years were
      compared between a PD group (n = 23) or a HD group (n = 44). In the PD group,
      nine patients (39%) developed DSA. The mean age of DSA patients was significantly
      higher than that of non-DSA patients (66.2 +/- 10.0 vs. 51.0 +/- 12.8 years, P =
      0.03). The frequency of cervical spine DSA did not show any difference between
      the PD and HD groups, but the frequency of lumbar spine DSA showed a significant
      difference (22% vs. 5%, P = 0.04). The serum beta-2 microglobulin (B2MG) level
      was significantly higher in PD patients than in HD patients (38.4 mg/L vs. 27.4
      mg/L, P = 0.0025). Mechanical stress such as elevation of the intra-abdominal
      pressure due to infusion of PD fluid (1500 mL to 2000 mL) for over 10 years might
      contribute to lumbar DSA in patients on long-term PD. 

PMID- 25851462
TI  - Health care managers' views on and approaches to implementing models for
      improving care processes.
AB  - AIM: To develop a deeper understanding of health-care managers' views on and
      approaches to the implementation of models for improving care processes.
      BACKGROUND: In health care, there are difficulties in implementing models for
      improving care processes that have been decided on by upper management.
      Leadership approaches to this implementation can affect the outcome. METHOD: In
      depth interviews with first- and second-line managers in Swedish hospitals were
      conducted and analysed using grounded theory. RESULTS: 'Coaching for
      participation' emerged as a central theme for managers in handling top-down
      initiated process development. The vertical approach in this coaching addresses
      how managers attempt to sustain unit integrity through adapting and translating
      orders from top management. The horizontal approach in the coaching refers to
      managers' strategies for motivating and engaging their employees in
      implementation work. CONCLUSION AND IMPLICATIONS FOR NURSING MANAGEMENT:
      Implementation models for improving care processes require a coaching leadership
      built on close manager-employee interaction, mindfulness regarding the pace of
      change at the unit level, managers with the competence to share responsibility
      with their teams and engaged employees with the competence to share
      responsibility for improving the care processes, and organisational structures
      that support process-oriented work. Implications for nursing management are the
      importance of giving nurse managers knowledge of change management.

PMID- 25851463
TI  - Aristotle, Hume and the goals of medicine.
AB  - Whilst medicine is now an immense global industry clinicians often appear unclear
      as to its goals. This paper uses two philosophical steps to clarify our
      conceptualization of health and thus our goals for healthcare. Firstly,
      clinicians need to understand the significance of Hume's fact / value distinction
      in medicine, for medicine relies on both facts and values. Secondly clinicians
      need a better specified definition of 'health' to use as a goal for healthcare.
      Aristotle's model of human flourishing is used as the starting point for a new
      conceptualization of health. 

PMID- 25851464
TI  - Polydentate chalcogen reagents for the facile preparation of Pd2 and Pd4
      complexes.
AB  - The silylated organochalcogen reagents 1,2-(Me3SiSCH2)2C6H4, and 1,2
      (Me3SiSeCH2)2C6H4, were prepared from the corresponding organobromides and
      lithium trimethylsilanechalcogenolate Li[ESiMe3] (E = S, Se). They have been
      characterized by multinuclear NMR spectroscopy ((1)H, (13)C, (77)Se) and
      electrospray ionization mass spectrometry. and react under mild conditions with
      (1,3-bis(diphenylphosphino)propane)palladium(ii) chloride, [PdCl2(dppp)], to
      provide the dinuclear organochalcogenolate-bridged complexes [(dppp)2Pd2-MU
      kappa(2)S-{1,2-(SCH2)2C6H4}]X2, []X2 and [(dppp)2Pd2-MU-kappa(2)Se-{1,2
      (SeCH2)2C6H4}]X2, []X2 (X = Cl, Br) in good yield, respectively. Furthermore, the
      tetranuclear palladium complex [(dppp)4Pd4-MU-kappa(4)S-{1,2,4,5-(SCH2)4C6H2}]X4,
      []X4 (X = Cl, Br) can be synthesized from the reaction of the
      tetrathiotetrasilane 1,2,4,5-(Me3SiSCH2)4C6H2, and [PdCl2(dppp)]. The structures
      of []X2, []X2 and []X4 were determined by single crystal X-ray diffraction
      methods. A variety of NMR experiments including two-dimensional homonuclear and
      heteronuclear correlated spectra were used to probe the solution behaviour of the
      dinuclear complexes in more detail. These complexes were further characterized by
      electrospray ionization (ESI) mass spectrometry, and for []X2 and []X2, UV-Vis
      absorption spectroscopy. 

PMID- 25851465
TI  - HLA-DQ allele-restricted activation of nitroso sulfamethoxazole-specific CD4
      positive T lymphocytes from patients with cystic fibrosis.
AB  - BACKGROUND: For certain HLA allele-associated drug hypersensitivity reactions,
      the parent drug has been shown to associate directly with the risk allele. In
      other forms of hypersensitivity, HLA risk alleles have not been identified and T
      cells are activated in an allele unrestricted manner. Chemically reactive drug
      metabolites bind to multiple proteins; thus, it is assumed that the derived
      peptide antigens interact with a number of HLA molecules to activate T cells;
      however, HLA restriction of the drug metabolite-specific T-cell response has not
      been studied. OBJECTIVE: To utilize T cells from sulfamethoxazole (SMX)
      hypersensitive patients with cystic fibrosis to examine the HLA molecules that
      interact with nitroso SMX (SMX-NO)-derived antigens. METHODS: T-cell clones were
      generated from 4 hypersensitive patients. Drug-specific proliferative responses
      and cytokine secretion were measured. Anti-human class I and class II antibodies
      were used to analyse HLA restriction. Antigen-presenting cells expressing
      different HLA molecules were used to determine the alleles involved in the
      presentation of SMX-NO-derived antigens to T cells. RESULTS: A total of 976
      clones were tested for SMX-NO reactivity. Thirty-nine CD4+ clones were activated
      with SMX-NO and found to proliferate and secrete cytokines. The SMX-NO-specific
      response was blocked with an antibody against HLA-DQ. SMX-NO-specific responses
      were detected with antigen-presenting cells expressing HLA-DQB1*05:01 (patient 1)
      and HLA-DQB1*02:01 (patient 2), but not other HLA-DQB1 alleles. CONCLUSION AND
      CLINICAL RELEVANCE: HLA-DQ plays an important role in the activation of SMX-NO
      specific CD4+ T cells. Detection of HLA-DQ allele-restricted responses suggests
      that T cells are activated by a limited repertoire of SMX-NO-modified peptides.

PMID- 25851467
TI  - Usefulness of a tailored metallic Y stent for the treatment of complex post-lung
      transplant bronchial stenosis.

PMID- 25851466
TI  - Combination of liver biopsy with MELD-XI scores for post-transplant outcome
      prediction in patients with advanced heart failure and suspected liver
      dysfunction.
AB  - BACKGROUND: Functional and structural liver abnormalities may be found in
      patients with advanced heart failure (HF). The Model of End-Stage Liver Disease
      Excluding INR (MELD-XI) score allows functional risk stratification of HF
      patients on and off anti-coagulation awaiting heart transplantation (HTx), but
      these scores may improve or worsen depending on bridging therapies and during
      time on the waiting list. Liver biopsy is sometimes performed to assess for
      severity of fibrosis. Uncertainty remains whether biopsy in addition to MELD-XI
      improves prediction of adverse outcomes in patients evaluated for HTx. METHODS:
      Sixty-eight patients suspected of advanced liver disease underwent liver biopsy
      as part of their HTx evaluation. A liver risk score (fibrosis-on-biopsy + 1) *
      MELD-XI was generated for each patient. RESULTS: Fifty-two patients were listed,
      of whom 14 had mechanical circulatory support (MCS). Thirty-six patients
      underwent transplantation and 27 patients survived >=1 year post-HTx (74%, as
      compared with 88% average 1-year survival in HTx patients without suspected liver
      disease; p < 0.01). Survivors had a lower liver risk score at evaluation for HTx
      (31.0 +/- 20.4 vs 65.2 +/- 28.6, p < 0.01). A cut-point of 45 for liver risk
      score was identified by receiver-operating-characteristic (ROC) analysis. In the
      analysis using Cox proportional hazards models, a liver risk score >=45 at
      evaluation for HTx was associated with greater risk of death at 1 year post-HTx
      compared with a score of <45 in both univariable (HR 3.94, 95% CI 1.77-8.79, p <
      0.001) and multivariable (HR 4.35, 95% CI 1.77-8.79, p < 0.001) analyses.
      Patients who died <1 year post-HTx had an increased frequency of acute graft
      dysfunction (44.4% vs 3.7%, p = 0.009), longer ventilation times (55.6% vs 11.1%,
      p = 0.013) and severe bleeding events (44.4% vs 11.1%, p = 0.049). The liver risk
      score at evaluation for HTx also predicted 1-year mortality after HTx listing (p
      < 0.001). CONCLUSIONS: Patients with HF and advanced liver dysfunction are high
      risk HTx candidates. Liver biopsy in addition to MELD-XI improves risk
      stratification of patients with advanced HF and suspected irreversible liver
      dysfunction.

PMID- 25851468
TI  - Effect of Anti-Sticking Nanostructured Surface Coating on Minimally Invasive
      Electrosurgical Device in Brain.
AB  - The purpose of the present study was to examine the extent of thermal injury in
      the brain after the use of a minimally invasive electrosurgical device with a
      nanostructured copper-doped diamond-like carbon (DLC-Cu) surface coating. To
      effectively utilize an electrosurgical device in clinical surgery, it is
      important to decrease the thermal injury to the adjacent tissues. The surface
      characteristics and morphology of DLC-Cu thin film was evaluated using a contact
      angle goniometer, scanning electron microscopy, and atomic force microscopy.
      Three-dimensional biomedical brain models were reconstructed using magnetic
      resonance images to simulate the electrosurgical procedure. Results indicated
      that the temperature was reduced significantly when a minimally invasive
      electrosurgical device with a DLC-Cu thin film coating (DLC-Cu-SS) was used.
      Temperatures decreased with the use of devices with increasing film thickness.
      Thermographic data revealed that surgical temperatures in an animal model were
      significantly lower with the DLC-Cu-SS electrosurgical device compared to an
      untreated device. Furthermore, the DLC-Cu-SS device created a relatively small
      region of injury and lateral thermal range. As described above, the biomedical
      nanostructured film reduced excessive thermal injury with the use of a minimally
      invasive electrosurgical device in the brain. 

PMID- 25851469
TI  - Assessment of a Four-View Mammographic Image Feature Based Fusion Model to
      Predict Near-Term Breast Cancer Risk.
AB  - The purpose of this study was to develop and assess a new quantitative four-view
      mammographic image feature based fusion model to predict the near-term breast
      cancer risk of the individual women after a negative screening mammography
      examination of interest. The dataset included fully-anonymized mammograms
      acquired on 870 women with two sequential full-field digital mammography
      examinations. For each woman, the first "prior" examination in the series was
      interpreted as negative (not recalled) during the original image reading. In the
      second "current" examination, 430 women were diagnosed with pathology verified
      cancers and 440 remained negative ("cancer-free"). For each of four bilateral
      craniocaudal and mediolateral oblique view images of left and right breasts, we
      computed and analyzed eight groups of global mammographic texture and tissue
      density image features. A risk prediction model based on three artificial neural
      networks was developed to fuse image features computed from two bilateral views
      of four images. The risk model performance was tested using a ten-fold cross
      validation method and a number of performance evaluation indices including the
      area under the receiver operating characteristic curve (AUC) and odds ratio (OR).
      The highest AUC = 0.725 +/- 0.026 was obtained when the model was trained by gray
      level run length statistics texture features computed on dense breast regions,
      which was significantly higher than the AUC values achieved using the model
      trained by only two bilateral one-view images (p < 0.02). The adjustable OR
      values monotonically increased from 1.0 to 11.8 as model-generated risk score
      increased. The regression analysis of OR values also showed a significant
      increase trend in slope (p < 0.01). As a result, this preliminary study
      demonstrated that a new four-view mammographic image feature based risk model
      could provide useful and supplementary image information to help predict the near
      term breast cancer risk. 

PMID- 25851471
TI  - B-type natriuretic peptide response and reverse left ventricular remodeling after
      surgical correction of functional mitral regurgitation in patients with advanced
      cardiomyopathy.
AB  - BACKGROUND: Restrictive mitral annuloplasty (RMA) can reverse left ventricular
      (LV) remodeling and reduce plasma B-type natriuretic peptide (BNP), a surrogate
      biomarker of heart failure. However, the relationship between reverse LV
      remodeling and plasma BNP changes after RMA is poorly defined. We explored the
      main hemodynamic factors contributing to change in plasma BNP after RMA in
      patients with functional mitral regurgitation (MR). METHODS: Twenty-four patients
      with moderate to severe functional MR secondary to LV systolic dysfunction
      [ejection fraction (EF) <40%] underwent 64-row multidetector computed tomography
      (MDCT) before and 1.4 months after RMA. LV end-diastolic volume index (EDVI), end
      systolic volume index (ESVI), LVEF, and regional and global end-systolic wall
      stress (ESS) were calculated from 3-dimensional MDCT images, with blood samples
      for plasma BNP measurement collected the same day. RESULTS: After RMA, LV volumes
      and global ESS were decreased, while LVEF improved (all p<0.01). There were
      significant correlations between changes in LVEDVI and LVESVI (r=0.90, p<0.0001),
      LVESVI and global ESS (r=0.54, p=0.006), and global ESS and LVEF (r=-0.60,
      p=0.002). The median value for the plasma BNP also decreased from 597 pg/ml
      [interquartile range (IQR), 360-934 pg/ml] to 207 pg/ml (IQR, 124-271 pg/ml), in
      association with changes in LVEDVI (r=0.47, p=0.019), LVESVI (r=0.56, p=0.004),
      LVEF (r=-0.60, p=0.002), and global ESS (r=0.74, p<0.0001). Multivariate
      regression analysis showed that global ESS change was the strongest contributor
      to change in natural-log-transformed plasma BNP (standardized partial regression
      coefficient=0.59, p=0.004), indicating a strong association between decrease in
      LV afterload and reduction in plasma BNP level after RMA. CONCLUSIONS: There may
      be a significant association between LV reverse remodeling and plasma BNP change
      after RMA. Furthermore, LV end-systolic myocardial stress may be the key
      mechanical stimulus influencing plasma BNP after surgical correction for
      functional MR. Whether these favorable BNP responses and reverse remodeling can
      predict improved survival requires further study.

PMID- 25851473
TI  - Right ventricular outflow muscle in tetralogy of Fallot: Histologic and
      immunohistochemical monoclonal antibody analysis.
AB  - To evaluate progressive muscular right ventricular outflow tract (RVOT)
      obstruction in tetralogy of Fallot (TOF), we hypothesized that this tissue would
      demonstrate more prominent selected immunohistochemical markers of myogenous cell
      differentiation, growth factor/receptor, and extracellular matrix. Sections of
      formalin-fixed, paraffin-embedded myectomy tissue obtained from RVOT at the time
      of surgical correction of TOF (n = 32; ages = 3 months through 13 years) were
      compared with age-matched tissue from the RVOT of normal control hearts (n = 12)
      obtained at autopsy after non-cardiac death. Examining by light microscopy slides
      stained with a combination of hematoxylin and eosin and elastic trichrome
      revealed cardiomyocyte (CM) hypertrophy, extensive myofiber disarray,
      trabeculation, multinucleation (more than two nuclei per myocyte), fibrosis, and
      thick-walled coronary arteries within the myocardium of TOF tissue. The
      endocardium from TOF specimens was thickened and hypercellular with prominent
      fibrosis and elastosis. Mitosis was not observed. At the interface between the
      endocardium and myocardium, the TOF specimens demonstrated myocyte dispolarity
      (orientation of CMs perpendicular to the endocardial surface), vascularization,
      and fibrosis. Immunohistochemical studies were performed using monoclonal
      antibodies to vimentin, desmin, muscle-specific actin (MSA), epidermal growth
      factor (EGF), epidermal growth factor receptor (EGFR), and laminin. Compared to
      the tissue from controls, TOF tissue showed a pattern of upregulated expression
      of epitopes within the endocardium and adjacent subendocardial myocardium.
      Decoration for MSA, vimentin, desmin, and EGFR highlighted the zonal nature of
      this tissue hyperactivity. Laminin prominently outlined endocardial cells,
      subendocardial CMs, and interface vessels in TOF tissue compared to the remainder
      of the myocardium and tissue from controls. Overall, changes in TOF were age
      related, with older patients showing less zonal myocardial reactivity. These
      findings provide evidence for an ongoing, complex remodeling of the RVOT muscle
      in TOF. 

PMID- 25851472
TI  - Patients with both CYP2C19 loss-of-function allele and peripheral endothelial
      dysfunction are significantly correlated with adverse cardiovascular events
      following coronary stent implantation.
AB  - BACKGROUND: There is some controversy regarding the effect of CYP2C19
      polymorphism on clinical outcome in patients receiving dual antiplatelet therapy
      (DAPT). Peripheral endothelial dysfunction has recently been reported to predict
      adverse cardiovascular events. We hypothesized that CYP2C19 loss-of-function
      (LOF) allele carriers with peripheral endothelial dysfunction had worse
      prognosis. The aim of this study was to evaluate an additive effect of peripheral
      endothelial dysfunction on clinical outcome following percutaneous coronary
      intervention (PCI) in patients with a CYP2C19 variant. METHODS: We enrolled 434
      patients on DAPT following PCI. CYP2C19 genotype was examined, and we divided
      patients into two groups: carriers, who had at least one CYP2C19 LOF allele, and
      non-carriers. Peripheral endothelial dysfunction was examined using reactive
      hyperemia-peripheral arterial tonometry index (RHI), and we divided patients into
      low and high RHI. Thus, subjects were divided into four groups, and clinical
      events were followed up. RESULTS: A total of 55 patients had a cardiovascular
      event. Kaplan-Meier analysis demonstrated a significantly higher probability of
      cardiovascular events in carriers with low RHI (log-rank test: p=0.007).
      Multivariate Cox proportional hazards analysis identified both CYP2C19 LOF allele
      possession (hazard ratio (HR): 1.94; 95% confidence interval (CI): 1.1-3.69;
      p=0.045) and low RHI (HR: 2.15; 95% CI: 1.22-3.78; p=0.008) as independent and
      significant predictors of future cardiovascular events. CONCLUSIONS: CYP2C19 LOF
      allele carriers with peripheral endothelial dysfunction were significantly
      correlated with cardiovascular events. The additional evaluation of peripheral
      endothelial function along with CYP2C19 polymorphism might improve risk
      stratification after coronary stent implantation.

PMID- 25851474
TI  - Tuberculous aortitis with coronary ostial and left ventricular outflow
      obstruction: Unusual cause of sudden unexpected death.
AB  - Tuberculous aortitis is a distinct, but uncommon, cause of thoracic and abdominal
      aortic aneurysms. We report an unusual case of tuberculous aortitis in a 12-year
      old girl that resulted in her sudden death. The patient suffered from undiagnosed
      primary pulmonary tuberculosis affecting the apical region of her right lower
      lobe, with regional hilar lymphadenopathy. The granulomatous inflammatory process
      spread from the hilar lymph nodes to the aortic root, leading to tuberculous
      aortitis and the formation of an intraluminal tuberculoma just superior to the
      aortic valve. The tuberculoma also involved the ostia and proximal portions of
      both coronary arteries, resulting in obstruction of the coronary arteries in
      addition to the left ventricular outflow tract. The consequent myocardial fiber
      hypertrophy and interstitial fibrosis predisposed the patient to the development
      of fatal arrhythmias that most probably accounted for her sudden death. 

PMID- 25851475
TI  - Endomyocardial biopsy findings in patients with ventricular arrhythmias of
      unknown origin.
AB  - To evaluate possible occult myocardial disease in patients with ventricular
      arrhythmias of unknown origin, over 11 years right ventricular endomyocardial
      biopsies (EMB) were performed on 80 consecutive such patients (29 Females, 51
      Males; median age 42 years). Seventy-one (89%) had ventricular tachycardia or
      fibrillation, 7 (9%) had complex ventricular arrhythmias, and 2 (3%) had
      premature ventricular beats. None showed clinical evidence of congestive heart
      failure or significant coronary artery or valvular disease. Endomyocardial
      biopsies revealed pathologic changes in 70 out of 80 patients (88%). Of the 70
      affected, 39 (56%) had nonspecific changes consistent with cardiomyopathy (e.g.,
      myofiber hypertrophy, interstitial and perivascular fibrosis, and vascular
      sclerosis); 6 (9%) had active myocarditis (Myo); 7 (10%) had borderline Myo; 7
      (10%) had small vessel disease; 6 (9%) had changes consistent with arrhythmogenic
      cardiomyopathy; 2 (3%) had amyloidosis; 2 (3%) had microfibrillar cardiomyopathy,
      and one (1.0%) showed intravascular organizing thrombus. Thus, EMB reveals a
      variety of abnormalities in the majority of patients presenting with ventricular
      arrhythmias without clinical evidence of structural heart disease. 

PMID- 25851476
TI  - Morphology of the atrioventricular valve in asplenia syndrome: A peculiar type of
      atrioventricular canal defect.
AB  - The high risk of atrioventricular (AV) valve regurgitation is a major point of
      concern in the natural history of patients with atrioventricular canal defect
      (AVCD) and asplenia syndrome (AS). The morphology of the common AV valve in
      patients with AVCD and AS was therefore studied and compared with the anatomy of
      patients with AVCD but with atrial situs solitus. We compared the anatomic
      features of hearts with common AV valve (ventricular loop; AV valve alignment on
      ventricles; number of leaflets; number and morphology of papillary muscles and
      relationship of the bridging leaflets with the ventricular septum) in the hearts
      of 33 patients with AVCD and asplenia syndrome (Group 1) with those of 44
      patients with common AV valve, complete AVCD, and atrial situs solitus (Group 2).
      Hearts featuring asplenia syndrome showed a significantly higher occurrence of
      anomalies of the ventricular loop (p < .0001), right ventricular dominance (p <
      .01), and a reduced number of valvular leaflets and papillary muscles (p <
      .0005). On the contrary, hearts with situs solitus of the atria showed a
      significantly higher frequency of balanced ventricles (p < .0001) and a common AV
      valve with five leaflets and five papillary muscles (p < .000001). These data
      suggest that AVCDs in association with asplenia syndrome present morphologic
      peculiarities that may be considered as the substrate for the abnormal
      regurgitation. Recognizing the presence of these features could be of great value
      for the planning of a specific surgical treatment. These anatomic differences
      support the hypothesis of a genetic heterogeneity of AVCDs. 

PMID- 25851477
TI  - Heart-lung transplantation: Cardiac clinicopathological correlations.
AB  - Reports on heart-lung transplantation emphasize the pathology of the transplanted
      lungs. This study is a clinicopathological assessment of cardiac pathology in the
      hearts transplanted as part of the combined heart-lung block. Seventy-five
      consecutive heart-lung transplants (H-LTx) performed between 1981 and 1989 were
      studied. Endomyocardial biopsy, autopsy and clinical data were analyzed for
      information on cardiac rejection, graft coronary disease, transplant survival and
      the presence of obliterative bronchiolitis and compared with controls. The
      controls consisted of 391 heart transplants (HTx) performed in 361 recipients
      over the same time period. Sixty-three adults and nine children received H-LTx
      (48.6% male; 51.4% female). In this study, H-LTx were performed primarily for
      Eisenmenger's complex (33 72 ) and primary pulmonary hypertension (28 72 ). At 1
      year H-LTx survival was 63.88%, versus 81.54% in HTx alone and 63.63% in lung
      transplant recipients without heart grafts. The results showed that H-LTx
      patients have less cardiac rejection compared to patients who undergo HTx alone
      (p < .005). Only 40% of H-LTx recipients developed acute cardiac rejection in the
      initial 3 months posttransplantation (post-Tx), compared with 80% of HTx
      controls. Only 4% of H-LTx recipients developed cardiac rejection after the
      initial 6 months. No cardiac rejection was observed in the initial 5 years post
      Tx in 49.9% of H-LTx. Graft coronary disease was seen in 7.73% of H-LTx within
      the first 5 years post-Tx compared with 25.87% in HTx recipients alone (p <
      .005). Obliterative bronchiolitis (OB) was present in 71.43% of H-LTx with graft
      coronary disease, compared to OB in only 41.38% of H-LTx without graft coronary
      disease (p < .05). In conclusion, H-LTx recipients have less acute cardiac
      rejection episodes than HTx recipients alone (p < .005). Most cardiac rejection
      in H-LTx occurs within the initial 6 months. In addition, H-LTx recipients
      develop less graft coronary disease than HTx recipients (p < .005). Obliterative
      bronchiolitis and graft coronary disease may be the result of the same
      immunological process, as 71.43% of H-LTx with graft coronary disease also had
      OB. Survival for H-LTx patients is more similar to that of lung transplant (LTx)
      patients alone than that of heart transplants alone, suggesting that it is the
      pulmonary pathology portion, rather than the cardiac pathology portion, in
      combined H-LTx transplants that contributes more to H-LTx survival. 

PMID- 25851478
TI  - Myasthenia gravis-associated systemic vasculitis and myocarditis with involvement
      of the cardiac conducting tissue.
AB  - We describe unexpected autopsy findings in an elderly woman with myasthenia
      gravis (MG) who had myocarditis of the working and conducting myocardium and
      coronary and renal vasculitis. Myasthenia gravis, characterized by autoantibodies
      to the acetylcholine receptor in the postsynaptic cell membrane, may be
      associated with other autoimmune disorders. An additional manifestation of
      autoimmunity is the presence of heart muscle antibodies, which may be the basis
      for myocarditis, which has been reported in up to 60% of MG patients at autopsy.
      Although myocarditis of the working myocardium is rather common, conduction
      system myocarditis and systemic vasculitis have not been previously reported in
      MG. 

PMID- 25851479
TI  - Severe postcardiac-transplant rejection associated with recurrence of giant cell
      myocarditis.
AB  - Giant cell myocarditis is a disease of unknown etiology with several
      controversial aspects: clinical course, therapeutic management, recurring risk
      after heart transplantation, and histopathological factors. We report a case of
      giant cell myocarditis that recurred after orthotopic heart transplantation and
      an uneventful postoperative period. The myocardial inflammatory process in this
      patient showed various evolutive phases: an acute onset of diffuse giant cell
      myocarditis, an evolution into a granulomatous form of inflammation within the
      explanted heart, and a recurrence with multiple giant cell inflammatory
      infiltrates in the transplanted heart. Moreover, the patient presented a severe
      clinical course after surgery with precocious and continuous acute rejections
      despite the repeated immunosuppressive treatments. In this article we discuss the
      morphological aspects of the disease and the postoperative course of this case in
      relation to the possible immune dysregulation of patients affected by myocarditis
      before heart transplantation. 

PMID- 25851480
TI  - Cardiac pentastomiasis and tuberculosis: The worm-eaten heart.
AB  - We report an autopsy case of disseminated tuberculosis and a coexisting,
      extremely rare parasitic zoonosis: pentastomiasis. The parasite was incidentally
      found in the pericardial sac and epicardium, associated with tuberculous
      pericarditis, in a 43-year-old woman from Georgia with presumptive Acquired
      Immunodeficiency Syndrome (AIDS). The cuticle was the only remaining intact
      structure of the parasite. The internal organs had undergone autolysis, but
      recognizable features were apparent. Gross and microscopic findings were highly
      suggestive of pentastomid species. The ultrastructure of the cuticle was
      consistent with a pentastomid arthropod. This is one of the few cases of visceral
      pentastomiasis reported in North America, and the first known example of heart
      involvement. The association of the parasitic infection and tuberculous
      pericarditis makes the case even more unusual. 

PMID- 25851481
TI  - Displacement of a commissure of the "Intact" porcine bioprosthesis resulting in
      valvular insufficiency.

PMID- 25851482
TI  - Definition of the arterial intima.

PMID- 25851483
TI  - Historical and contemporary cultural ecosystem service values in the rapidly
      urbanizing city state of Singapore.
AB  - Cultural ecosystem services are a function of people and place, so may change as
      a location transitions from rural to urban. Singapore has undergone rapid
      urbanization after its independence in 1965, with a concomitant decline in
      natural habitat extent and accessibility. Using coastal mangrove forests as a
      case study habitat, changing cultural values were explored with a novel array of
      techniques, including qualitative archival analysis (photographs, oral
      histories), current sources (publically uploaded social media photographs), and
      surveys of (a) the general public and (b) visitors to publically accessible
      mangroves. Cultural value changed through time, with a significant transition
      from intrinsic, intrapersonal values (spiritual, cultural heritage) to
      instrumental, interpersonal values (recreation, education). Additionally,
      cultural value varied between different mangroves depending on their public
      accessibility, and the evolving degree of human interaction with the ecosystem as
      urban development occured. Cultural values change as development transitions,
      though mangroves still play an important cultural role in a heavily urbanized
      environment. 

PMID- 25851484
TI  - Decline of traditional rice farming constrains the recovery of the endangered
      Asian crested ibis (Nipponia nippon).
AB  - Traditional agriculture benefits a rich diversity of plants and animals. The
      winter-flooded rice fields in the Qinling Mountains, China, are the last refuge
      for the endangered Asian crested ibis (Nipponia nippon), and intensive efforts
      have been made to protect this anthropogenic habitat. Analyses of multi-temporal
      satellite data indicate that winter-flooded rice fields have been continuously
      reduced across the current range of crested ibis during the past two decades. The
      rate of loss of these fields in the core-protected areas has unexpectedly
      increased to a higher level than that in non-protected areas in the past decade.
      The best fit (R (2) = 0.87) numerical response model of the crested ibis
      population shows that a reduction of winter-flooded rice fields decreases
      population growth and predicts that the population growth will be constrained by
      the decline of traditional winter-flooded rice fields in the coming decades. Our
      findings suggest that the decline of traditional rice farming is likely to
      continue to pose a threat to the long-term survival and recovery of the crested
      ibis population in China.

PMID- 25851485
TI  - Nalmefene for Reducing Alcohol Consumption in People with Alcohol Dependence: An
      Evidence Review Group Perspective of a NICE Single Technology Appraisal.
AB  - As part of its single technology appraisal process, the National Institute for
      Health and Care Excellence (NICE) invited the company (Lundbeck) marketing
      nalmefene (Selincro) to submit evidence of its clinical and cost effectiveness
      for reducing alcohol consumption in people with alcohol dependence. The School of
      Health and Related Research Technology Appraisal Group at the University of
      Sheffield was commissioned to act as the independent Evidence Review Group (ERG)
      and to produce a critical review of the company's submission to NICE. The
      clinical evidence was derived from three phase III, company-sponsored,
      randomised, double-blind, placebo-controlled trials in adults with a diagnosis of
      alcohol dependence comparing nalmefene, taken on an as-needed basis, in
      conjunction with psychosocial support with placebo in conjunction with
      psychosocial support. Psychosocial support was provided in the form of BRENDA, an
      intervention of lower intensity than that recommended in NICE Clinical Guideline
      115 (NICE CG115). Post-hoc subgroup analyses were conducted in people who were
      drinking at high or very high risk levels at baseline and maintained this level
      of drinking during the screening phase prior to randomisation. This subgroup
      forms the licensed population. There were a number of limitations and
      uncertainties in the clinical evidence base which warrant caution in its
      interpretation. In particular, the post-hoc subgroup analyses and high dropout
      rates in the three nalmefene studies meant that the inference of treatment
      effects might be confounded. The company's economic evaluation showed that use of
      nalmefene in conjunction with psychosocial support in the form of BRENDA
      dominated the use of BRENDA in conjunction with placebo, providing more quality
      adjusted life-years (QALYs) at a reduced cost. However, this evaluation did not
      meet the final scope issued by NICE, which specified that the comparator should
      be psychological intervention as defined in NICE CG115. The ERG produced
      alternative cost per QALY values for the comparison undertaken by the company and
      suggested three further comparisons deemed relevant: (1) nalmefene with
      psychological intervention as defined in NICE CG115; (2) delayed use of nalmefene
      in those who did not respond to psychological intervention as recommended in NICE
      CG115 alone; and (3) use of naltrexone outside of its marketing authorisation.
      The ERG thought it probable that using nalmefene in only those people who do not
      respond to psychological intervention alone was likely to be more cost effective
      compared with its immediate use in the entire licensed population. The Appraisal
      Committee accepted the comparison with psychosocial support in the form of BRENDA
      and believed that the most plausible cost per QALY was likely to be below L5100.
      Therefore, the Appraisal Committee concluded that nalmefene in conjunction with
      psychosocial support was a cost effective use of NHS resources compared with
      psychosocial support alone for treating people with alcohol dependence drinking
      at a high risk level, without physical withdrawal symptoms and not requiring
      immediate assisted withdrawal from alcohol.

PMID- 25851486
TI  - Characterizing Heterogeneity Bias in Cohort-Based Models.
AB  - PURPOSE: Previous research using numerical methods suggested that use of a cohort
      based model instead of an individual-based model can result in significant
      heterogeneity bias. However, the direction of the bias is not known a priori. We
      characterized mathematically the conditions that lead to upward or downward bias.
      METHOD: We used a standard three-state disease progression model to evaluate the
      cost effectiveness of a hypothetical intervention. We solved the model
      analytically and derived expressions for life expectancy, discounted quality
      adjusted life years (QALYs), discounted lifetime costs and incremental net
      monetary benefits (INMB). An outcome was calculated using the mean of the input
      under the cohort-based approach and the whole input distribution for all persons
      under the individual-based approach. We investigated the impact of heterogeneity
      on outcomes by varying one parameter at a time while keeping all others constant.
      We evaluated the curvature of outcome functions and used Jensen's inequality to
      determine the direction of the bias. RESULTS: Both life expectancy and QALYs were
      underestimated by the cohort-based approach. If there was heterogeneity only in
      disease progression, total costs were overestimated, whereas QALYs gained,
      incremental costs and INMB were under- or overestimated, depending on the
      progression rate. INMB was underestimated when only efficacy was heterogeneous.
      Both approaches yielded the same outcome when the heterogeneity was only in cost
      or utilities. CONCLUSION: A cohort-based approach that does not adjust for
      heterogeneity underestimates life expectancy and may underestimate or
      overestimate other outcomes. Characterizing the bias is useful for comparative
      assessment of models and informing decision making.

PMID- 25851488
TI  - Endothelial cell icam-1 staining in human carotid arteries.
AB  - In this study human carotid artery specimens from 18 patients were examined by an
      en face technique to demonstrate the endothelial cell staining of intercellular
      adhesion molecule-1 (ICAM-1). Endothelial cells about the carotid bifurcation and
      within the post-stenotic region of the internal carotid artery were predominately
      polyhedral in shape with heterogenous but often intense ICAM-1 staining.
      Endothelium lining the partially stenosed lumen of the intern carotid orifice
      were elongated with ICAM-1 staining often polarized at the proximal end of the
      cell. There were two dominant patterns of ICAM-1 staining associated with
      polyhedral endothelial cells, cell border, and cell surface/nuclear profile
      staining. Polyhedral cells at the proximal end of the internal carotid artery
      stenosis appeared to have both patterns while those at the distal end were most
      often observed with only the cell surface expression pattern. Adherent leukocytes
      were mostly observed in association with polyhedral endothelial cells especially
      in the post-stenotic internal carotid and were uncommon within stenoses. These
      results indicate heterogeneity not only of endothelial cell morphology but also
      in the intensity and pattern of staining of ICAM-1 about atherosclerotic lesions.
      This may be indicative of different functional properties for ICAM-1 depending on
      anatomical localization and consequent hemodynamic stresses. 

PMID- 25851487
TI  - RECQ5-dependent SUMOylation of DNA topoisomerase I prevents transcription
      associated genome instability.
AB  - DNA topoisomerase I (TOP1) has an important role in maintaining DNA topology by
      relaxing supercoiled DNA. Here we show that the K391 and K436 residues of TOP1
      are SUMOylated by the PIAS1-SRSF1 E3 ligase complex in the chromatin fraction
      containing active RNA polymerase II (RNAPIIo). This modification is necessary for
      the binding of TOP1 to RNAPIIo and for the recruitment of RNA splicing factors to
      the actively transcribed chromatin, thereby reducing the formation of R-loops
      that lead to genome instability. RECQ5 helicase promotes TOP1 SUMOylation by
      facilitating the interaction between PIAS1, SRSF1 and TOP1. Unexpectedly, the
      topoisomerase activity is compromised by K391/K436 SUMOylation, and this provides
      the first in vivo evidence that TOP1 activity is negatively regulated at
      transcriptionally active chromatin to prevent TOP1-induced DNA damage. Therefore,
      our data provide mechanistic insight into how TOP1 SUMOylation contributes to
      genome maintenance during transcription. 

PMID- 25851489
TI  - Peculiarities of prevalence and morphology of congenital heart disease detected
      in utero.
AB  - Intrauterine echocardiography is changing our knowledge of congenital heart
      disease; cardiac defects diagnosed in utero have distinctive features of both
      prevalence and morphology when compared with those observed just after birth. We
      reviewed a series of 171 fetal heart conditions: 148 were diagnosed at
      intrauterine echocardiography, the diagnosis being verified at autopsy in 41, and
      23 were observed at the postmortem only. Peculiarities of prevalence consisted in
      an excess of various defects, such as hypoplastic left heart syndrome, atrial
      isomerism, pulmonary atresia, and atrioventricular and atrial septal defects, and
      in a reduced number of completely different conditions, such as transposition of
      great arteries and aortic coarctation. Differences in prevalence have been
      attributed to difficulties in diagnosing some particular anomalies in utero, to
      the selection of pregnancies undergoing screening, and to the special
      intrauterine evidence of some heart defects. Peculiarities in morphology result
      from the coexistence with extracardiac malformations, from the changes in shape
      conditioned by fetal hemodynamics, and from the intrauterine evolution of the
      morphology of some malformations. We concluded that the knowledge of these
      characteristic traits was helpful to cardiac pathologists, pediatric
      cardiologists, and obstetricians, and allowed the re-evaluation of the role of
      hemodynamic factors in remodeling the malformed cardiovascular appara-tus. 

PMID- 25851490
TI  - Severe congenital stenosis of the left coronary artery ostium and its possible
      pathogenesis according to current knowledge on coronary artery development.
AB  - We report a 72-year-old woman with severe congenital stenosis of the left
      coronary artery orifice and clinically significant atherosclerotic changes in
      both the right and left coronary arteries. The stenotic ostium was located at the
      point at which the left and posterior aortic valve leaflets joined to form the
      left commissure, just at the distal vertex of the left interleaflet triangle,
      between the left and posterior aortic sinuses. The right coronary artery was more
      developed in size than usual, whereas the left coronary artery consisted of a
      short left main coronary trunk that bifurcated into left anterior descending and
      left circumflex arteries. The left coronary artery system was filled retrogradely
      through two vessels proceeding from the right coronary artery, namely, the conal
      artery and a well-developed branch that ran across the interventricular septum.
      This abnormal arrangement of the coronary arteries showed striking functional
      similarities with atresia of the left main coronary artery. Current knowledge on
      the morphogenesis of the coronary arteries suggests that the present anomalous
      coronary artery pattern resulted from the penetration of the anticipated left
      coronary artery system into the aorta at a totally erroneus site. This hindered
      the normal development of the ostium, which subsisted as a punctiform,
      practically nonfunctional opening. 

PMID- 25851491
TI  - Inf lammatory Mass with Fibrinoid Necrosis of Vessels Caused by Methylene Blue
      Marking of a Colonic Polyp.
AB  - Methylene blue is a relatively non-toxic dye that is used in a variety of
      procedures including the marking of margins and skin flaps, identifying sinus and
      fistulous tracts, localizing islet cell tumors, and marking colonic polyps. It
      has been used intravascularly for the labeling of arteriovenous malformations or
      to find small bleeding sites. Few adverse effects have been reported with its
      use. We report an unusual case of an inflammatory mass secondary to transmural
      injection of methylene blue that resulted in fibrinoid necrosis of arterial media
      mimicking a necrotizing vasculitis. 

PMID- 25851492
TI  - Comparison of efficacy and toxicity profiles between paclitaxel/lobapoatin- and
      cisplatin/5-fluorouracil-based concurrent chemoradiotherapy of advanced
      inoperable oesophageal cancer.
AB  - BACKGROUND AND AIM: Current chemoradiotherapy doesn't usually effectively control
      oesophageal cancer progression. This study assessed the efficacy and toxicity
      profiles of paclitaxel/lobaplatin (TL)- and cisplatin/5-fluorouracil (PF)-based
      concurrent chemoradiotherapy (CCRT) in patients with advanced inoperable
      oesophageal cancer. METHODS: A total of such 68 patients was recruited and
      randomised to receive TL or PF-based CCRT. Radiotherapy was given at a total dose
      of 60-70 Gy over 6 weeks. In the TL group of patients, paclitaxel 60 mg/m(2) was
      administered intravenously on day 1, 8 and 15 and lobaplatin 30 mg/m(2) was
      administered on day 2 in two cycles at 3-week intervals. In the PF group,
      cisplatin 75 mg/m(2) was administered intravenously on day 1, and 5-fluorouracil
      500 mg/m(2) and leucovorin 200 mg/m(2) were administered intravenously daily for
      5 days in two cycles at 3-week intervals. Adverse events, treatment response and
      follow-up data were collected. RESULTS: The treatment response rates were 73.53%
      and 50.00% in the TL and PF groups respectively (P = 0.040). The median tumour
      progression-free survival (PFS) was 13.0 and 6.5 months in the TL and PF groups
      respectively (P = 0.034). Compared with PF group, the TL group demonstrated
      decreased grade 3/4 nausea and vomiting (5.88% vs 35.29%, P = 0.003), decreased
      granulocytopenia (11.76% vs 32.35%, P = 0.041) and platelet count reduction
      (32.5% vs 8.8%, P = 0.016). CONCLUSIONS: The TL treatment regimen demonstrated
      higher efficacy with less overall toxicity in patients with advanced inoperable
      oesophageal cancer compared with the PF regimen. Further study is warranted to
      validate our current observations.

PMID- 25851493
TI  - Dynamic material flow modeling: an effort to calibrate and validate aluminum
      stocks and flows in Austria.
AB  - A calibrated and validated dynamic material flow model of Austrian aluminum (Al)
      stocks and flows between 1964 and 2012 was developed. Calibration and extensive
      plausibility testing was performed to illustrate how the quality of dynamic
      material flow analysis can be improved on the basis of the consideration of
      independent bottom-up estimates. According to the model, total Austrian in-use Al
      stocks reached a level of 360 kg/capita in 2012, with buildings (45%) and
      transport applications (32%) being the major in-use stocks. Old scrap generation
      (including export of end-of-life vehicles) amounted to 12.5 kg/capita in 2012,
      still being on the increase, while Al final demand has remained rather constant
      at around 25 kg/capita in the past few years. The application of global
      sensitivity analysis showed that only small parts of the total variance of old
      scrap generation could be explained by the variation of single parameters,
      emphasizing the need for comprehensive sensitivity analysis tools accounting for
      interaction between parameters and time-delay effects in dynamic material flow
      models. Overall, it was possible to generate a detailed understanding of the
      evolution of Al stocks and flows in Austria, including plausibility evaluations
      of the results. Such models constitute a reliable basis for evaluating future
      recycling potentials, in particular with respect to application-specific
      qualities of current and future national Al scrap generation and utilization. 

PMID- 25851494
TI  - A rapid and reliable strategy for chromosomal integration of gene(s) with
      multiple copies.
AB  - Direct optimization of the metabolic pathways on the chromosome requires tools
      that can fine tune the overexpression of a desired gene or optimize the
      combination of multiple genes. Although plasmid-dependent overexpression has been
      used for this task, fundamental issues concerning its genetic stability and
      operational repeatability have not been addressed. Here, we describe a rapid and
      reliable strategy for chromosomal integration of gene(s) with multiple copies
      (CIGMC), which uses the flippase from the yeast 2-MUm plasmid. Using green
      fluorescence protein as a model, we verified that the fluorescent intensity was
      in accordance with the integration copy number of the target gene. When a narrow
      host-range replicon, R6K, was used in the integrative plasmid, the maximum
      integrated copy number of Escherichia coli reached 15. Applying the CIGMC method
      to optimize the overexpression of single or multiple genes in amino acid
      biosynthesis, we successfully improved the product yield and stability of the
      production. As a flexible strategy, CIGMC can be used in various microorganisms
      other than E. coli. 

PMID- 25851495
TI  - Alteration in peripheral blood concentration of certain pro-inflammatory
      cytokines in cows developing retention of fetal membranes.
AB  - Retention of fetal membranes (RFM) adversely affects the production and
      reproduction potential of the affected cows leading to huge economic loss.
      Physiological separation of fetal membranes is reported to be an inflammatory
      process. The present study compared the concentrations of certain pro
      inflammatory cytokines [Interleukin 1beta (IL-1), Interleukin 6 (IL-6),
      Interleukin 8 (IL-8) and Tumor necrosis factor alpha (TNF-alpha) between the cows
      that developed RFM (n=10) and the cows that expelled fetal membranes normally
      (n=10) to find out if they could serve as a predictive tool for RFM. Blood
      samples were collected from the cows from 30 days before expected parturition
      through day -21, day -14, day -7, day -5, day -3, day -1, on the day of
      parturition (day 0), day 1 postpartum and the pro-inflammatory cytokines were
      estimated in blood plasma by ELISA method. The IL-1beta concentration was
      significantly lower (P<0.05) in cows that developed RFM compared to those that
      expelled fetal membranes normally from 3 days before calving till the day of
      calving. The plasma concentrations of IL-6 and IL-8 were also lower (P<0.05) in
      cows that developed RFM than those calved normally. On the day of calving,
      significantly (P<0.05) lower concentrations of TNF-alpha was observed in cows
      that developed RFM compared to those expelled fetal membranes normally. It may be
      inferred that the concentrations of IL-1, IL-6, IL-8 and TNF-alpha around
      parturition were altered in cows developing RFM compared to those expelled fetal
      membranes normally. 

PMID- 25851496
TI  - Prognostic factors affecting cervical adenocarcinoma: 10 years experience in a
      single institution.
AB  - OBJECTIVES: We performed a population-based study to determine the significance
      of adenocarcinoma and to evaluate its behavior over the last 10 years among
      patients treated in the National cancer institute of Morocco. STUDY DESIGN: This
      is a retrospective study that was conducted in the national cancer institute of
      Morocco. Over a period of 10 years, we retrieved 350 cases of cervical invasive
      adenocarcinoma. Survival was analyzed according to the Kaplan-Meier method. A
      univariate analysis of prognostic factors was performed using the test of log
      rank. Cox regression model was used for the multivariate analysis of prognostic
      factors. RESULTS: Mean age at presentation was 46 years. Sixty seven percent of
      the patients had locally advanced stage. Radiotherapy was prescribed in 73.3 % of
      the cases. The mean follow-up time for surviving patients was 51 months. The 5
      year survival rates according to clinical stages were as follows, 76 and 62 % for
      stages I and II, respectively, 32 and 9 % for stages III and IV, respectively.
      Tumor stage, tumor grade, positive lymph nodes status, lymphovascular space
      involvement and patient's age were significant prognostic factors in a univariate
      analysis. While only stage and lymph node involvement remained significant
      independent predictors for survival in the multivariate analysis. CONCLUSION:
      Although in our country incidence of adenocarcinoma is lower than the ones
      reported in western countries, in general our results are consistent with those
      reported in the literature. Better outcomes are observed in both early stages and
      young patients. Also, we found that FIGO stage, grade and lymph node metastases
      to be significant prognostic factors for survival in cervical adenocarcinoma.

PMID- 25851497
TI  - Dysregulated microRNAs involved in the progression of cervical neoplasm.
AB  - PURPOSE: MicroRNAs (miRNAs) exhibit dysregulated expression in human cancer and
      play an important role in carcinogenesis. The aim of this study was to identify a
      distinct miRNA expression signature for cervical cancer and cervical
      intraepithelial neoplasia (CIN) and to investigate the function of deregulated
      miRNAs in cervical carcinoma. METHODS: A miRNA microarray was used to compare
      miRNA expression profiles in cervical cancer, CIN and normal cervical tissues.
      Real-time RT-PCR was used to validate the expression of 9 miRNAs in 103 cervical
      tissues. Bioinformatics programs were used to predict potential target genes and
      their function. Functional studies were performed to characterize the effect on
      cervical cancer cells by overexpression of miR-218 and miR-21. RESULTS: We
      identified deregulated miRNAs in cervical cancer and high-grade squamous
      intraepithelial lesions (HSIL). MiR-218 was the most downregulated (0.175-fold
      decrease) miRNA, and miR-21 was the most upregulated (5.67-fold increase) miRNA.
      In addition, the expression patterns of 9 miRNAs were validated by real-time RT
      PCR. Bioinformatics analyses and functional studies indicated that miR-218 and
      miR-21 may be involved in cancer invasion and metastasis. CONCLUSION: Our study
      demonstrated that miRNAs are aberrantly expressed in cervical cancer and cervical
      preneoplastic lesions. These miRNAs may be involved in the progression of
      cervical neoplasm as potential tumor suppressor genes or oncogenes.

PMID- 25851498
TI  - Conflicting umbilical artery Doppler findings in fetuses with trisomy 21.
AB  - OBJECTIVE: To assess differences between fetuses with isolated and non-isolated
      trisomy 21 in umbilical artery (UA) Doppler findings in the second and third
      trimester and to correlate those with placental histology. METHODS: Retrospective
      analysis of UA pulsatility index (PI) in 281 fetuses with trisomy 21. Cases were
      divided into isolated trisomy 21 (group I, n = 148, 52.7 %) and non-isolated
      trisomy 21 (group II, n = 133, 47.3 %). UA measurements were evaluated in five
      different time periods (A-E; <20 + 0 to >= 35 + 0 weeks) and were assigned
      histopathology of the placenta. RESULTS: In 118/281 (42 %) cases, UA measurement
      was abnormal. The frequency of PI values above the 95th percentile increased
      significantly with gestational age in both groups (period A 32.9 % vs. period E
      63.6 %, p < 0.0001). There was neither a difference in abnormal UA PI values
      between isolated and non-isolated cases [37.8 % (56/148) vs. 46.6 % (62/133)] nor
      a correlation to placental findings. CONCLUSIONS: Fetuses with trisomy 21 often
      present with elevated UA PI in the late second or third trimester, irrespective
      of small for gestational age growth, malformations or histopathological findings
      of impaired placentation.

PMID- 25851499
TI  - Large-Scale Computations in Chemistry: A Bird's Eye View of a Vibrant Field.

PMID- 25851500
TI  - A probabilistic method for determining cortical dynamics during seizures.
AB  - This work presents a probabilistic method for inferring the parameter ranges in a
      biologically relevant mathematical model of the cortex most likely to be
      producing seizures observed in an electrocorticogram (ECoG) signal from a human
      subject. Additionally, this method produces a probabilistic pathway of the
      temporal evolution of physiological state in the cortex over the course of
      individual seizures, leveraging a model of the cortex that describes cortical
      physiology. We describe ways in which these methods and results offer insights
      into seizure etiology and have the potential to suggest new treatment options. To
      directly account for the stochastic and noisy nature of the mathematical model
      and the ECoG signal, we use a probabilistic Bayesian framework to map features of
      ECoG segments onto a distribution of likelihoods over physiologically-relevant
      parameter states. A Hidden Markov Model (HMM) is then introduced to incorporate
      the belief that cortical physiology has both temporal continuity and also a
      degree of reproducibility between individual seizures. By inspecting the ratio of
      likelihoods between HMMs run under two possible parameter regions, both of which
      produce seizures in the model, we determine which physiological parameter regions
      are more likely to be causing the observed seizures. We show that between
      individual seizures, there is consistency in these likelihood ratios between
      hypothesized regions, in the temporal pathways calculated, and in the separation
      of seizure from non-seizure time segment likelihood maps. 

PMID- 25851501
TI  - Egg shell quality in Japanese quail: characteristics, heritabilities and genetic
      and phenotypic relationships.
AB  - The objective of the present study was to estimate heritabilities as well as
      genetic and phenotypic correlations for egg weight, specific gravity, shape
      index, shell ratio, egg shell strength, egg length, egg width and shell weight in
      Japanese quail eggs. External egg quality traits were measured on 5864 eggs of
      934 female quails from a dam line selected for two generations. Within the
      Bayesian framework, using Gibbs Sampling algorithm, a multivariate animal model
      was applied to estimate heritabilities and genetic correlations for external egg
      quality traits. The heritability estimates for external egg quality traits were
      moderate to high and ranged from 0.29 to 0.81. The heritability estimates for egg
      and shell weight of 0.81 and 0.76 were fairly high. The genetic and phenotypic
      correlations between egg shell strength with specific gravity, shell ratio and
      shell weight ranging from 0.55 to 0.79 were relatively high. It can be concluded
      that it is possible to determine egg shell quality using the egg specific gravity
      values utilizing its high heritability and fairly high positive correlation with
      most of the egg shell quality traits. As a result, egg specific gravity may be
      the choice of selection criterion rather than other external egg traits for
      genetic improvement of egg shell quality in Japanese quails. 

PMID- 25851502
TI  - The effects of educational interventions on pharmacists' knowledge, attitudes and
      beliefs towards low back pain.
AB  - BACKGROUND: Practitioner beliefs and attitudes towards low back pain (LBP)
      influence treatment decisions. Little is known about pharmacists' knowledge,
      attitudes and beliefs towards LBP. OBJECTIVES: To investigate the effect of
      educational interventions on pharmacists' knowledge, attitudes and beliefs
      towards LBP. Setting Sydney Metropolitan Area. METHODS: Knowledge, attitudes and
      beliefs was measured using the "Pharmacists' Back Beliefs Questionnaire", with
      items from two previously reported questionnaires on back beliefs. Responses from
      pharmacists attending a 2-h educational workshop on LBP (n = 204) and pharmacists
      recruiting participants for a LBP clinical trial (n = 66) were compared to
      responses from a control group of pharmacists (n = 65) to allow an evaluation of
      the two interventions. Responses from workshop participants were also evaluated
      before and after the session. Participants indicated their agreement with
      statements about LBP on a 5-point Likert scale. Preferred responses were based on
      guidelines for the evidence-based management of LBP. The primary analysis
      evaluated total score on the nine-inevitability items of the Back Beliefs
      Questionnaire ("inevitability score"). MAIN OUTCOME MEASURE: Inevitability score.
      RESULTS: There was no significant difference in inevitability score between LBP
      clinical trial pharmacists and the control group [mean difference (MD) 0.47 (95 %
      CI -1.35 to 2.29; p = 0.61)]. The educational workshop led to a significant and
      favourable change in inevitability score (MD 7.23 p < 0.001) and notable changes
      in responses to misconceptions regarding bed rest and the need for imaging (p <
      0.001) among participating pharmacists. CONCLUSIONS: Pharmacists attending the
      educational workshop provided the most compelling evidence that education
      specifically aimed at delivering evidence-based information can be successful in
      changing practitioner knowledge, beliefs and attitudes towards LBP.

PMID- 25851503
TI  - Antimicrobial stewardship activities in hospitals in Ireland and the United
      Kingdom: a comparison of two national surveys.
AB  - BACKGROUND: Best practice guidelines recommend that a multidisciplinary
      Antimicrobial Management Team (AMT) conduct antimicrobial stewardship (AMS)
      activities in hospitals. In order to continuously improve AMS activities in Irish
      hospitals it is important to benchmark performance by comparison with other
      countries. OBJECTIVE: To compare the membership of AMTs and AMS activities
      conducted in Irish and United Kingdom (UK) hospitals. METHODS: A postal
      questionnaire to determine the membership and activities of AMTs was issued to
      the specialist antimicrobial pharmacist or pharmacist in charge at all Irish
      Hospitals and all UK National Health Service Hospitals. The membership of AMTs
      and the extent of AMS activities conducted were compared between the countries.
      RESULTS: The response rates to the surveys were 73% (n = 51) in Ireland and 33%
      in the UK (n = 273). 57% of Irish respondents reported having an AMT compared to
      82% in the UK (p < 0.001). Significantly more AMTs in the UK had a specialist
      antimicrobial pharmacist on the team (95% UK, 69% Ireland, p < 0.001). A higher
      proportion of Irish respondents reported measuring the overall volume of
      antimicrobial prescribing (Ireland 85%, UK 72%, p = 0.057). A higher proportion
      of UK respondents reported measuring the appropriateness of antimicrobial
      prescribing (76% UK, 58% Ireland, p = 0.019) and the appropriateness of
      restricted antimicrobial prescribing (64% UK, 52% Ireland, p = 0.140).
      CONCLUSION: Irish and UK AMTs need to be supported to recruit and retain
      specialist antimicrobial pharmacists and to achieve higher rates of audit,
      prescription appropriateness review and feedback activities.

PMID- 25851504
TI  - Post-illness-onset risk of offending across the full spectrum of psychiatric
      disorders.
AB  - BACKGROUND: The link between psychotic disorders and violent offending is well
      established; knowledge about risk of post-illness-onset offending across the full
      spectrum of psychiatric disorders is lacking. We aimed to compare rates of any
      offending and violent offending committed after the onset of illness, according
      to diagnostic group, with population controls. METHOD: A 25% random sample of the
      Danish population (n = 521 340) was followed from their 15th birthday until
      offending occurred. Mental health status was considered as a time-varying
      exposure in a Poisson regression model used to examine the duration from service
      contact to the offence. RESULTS: Males with any psychiatric contact had an
      incidence rate ratio (IRR) of 2.91 [95% confidence interval (CI) 2.80-3.02] for
      any offending; 4.18 (95% CI 3.99-4.38) for violent offending. Associations were
      stronger for women (IRR 4.17, 95% CI 3.95-4.40 for any offending; 8.02, 95% CI
      7.20-8.94 for violent offending). Risk was similar across diagnostic groups for
      any offending in males, while variation between diagnostic groups was seen for
      male violent and female offending, both any and violent. CONCLUSIONS: Risk of
      offending, particularly violent offending, was elevated across a range of mental
      disorders following first contact with mental health services. The extent of
      variation in strength of effect across diagnoses differed by gender.

PMID- 25851505
TI  - Budgetary impact of the utilization of buprenorphine/naloxone sublingual film and
      tablet for Medicaid in the United States.
AB  - OBJECTIVES: The buprenorphine/naloxone combination for the treatment of opioid
      dependence is available in a film or tablet formulation. Recent retrospective
      studies demonstrated that treatment with the sublingual film formulation is
      associated with improved treatment retention and lower healthcare costs. In March
      2013, generic buprenorphine/naloxone tablets were approved in the US. A budget
      impact model was built to compare healthcare expenditures for different market
      shares of sublingual film and tablet. METHODS: A Markov model was developed to
      track a cohort of opioid dependent patients treated with sublingual film or
      tablet through the following treatment phases: initiation, maintenance,
      discontinuation, off-treatment and reinitiation. Transition probabilities and
      costs for each phase were estimated from the MarketScan Medicaid database for the
      period between 1 March 2010 and 30 June 2012. The total expenditure for the plan
      and expenditure per plan member per month were predicted over 5 years. Two market
      share scenarios were considered: 1) sublingual film is progressively replaced by
      generic tablet (current situation) and 2) the sublingual film holds a market
      share of 100%. RESULTS: Predicted total costs over 5 years were $6400 million
      when the sublingual film holds a market share of 100% (as per Scenario 2) which
      is lower than when sublingual film is progressively replaced by generic tablet
      (current situation as per Scenario 1) by $64 million. These savings were mostly
      driven by inpatient care ($56 million saved over 5 years), followed by emergency
      room care ($27 million) and pharmaceutical costs ($24 million). Costs of
      outpatient care attenuated the difference as they were predicted to be higher by
      $44 million in Scenario 2. The reduction in total cost per member per month
      reached $0.027 in the fifth year. Results were most sensitive to price rebates
      and to the probability of non-psychiatric hospitalization. CONCLUSIONS: While
      using the sublingual film formulation for more patients treated with
      buprenorphine/naloxone is predicted to increase outpatient care costs, it would
      generate savings in emergency care and hospitalizations. In the treatment of
      opioid dependence, total direct medical costs for Medicaid would be lower for
      sublingual film treated patients, at current drug prices.

PMID- 25851506
TI  - A Dynamical Basis Set for Generating Reaches.
AB  - The motor cortex was the one of the first cortical areas to be explored
      electrophysiologically, yet little agreement has emerged regarding its basic
      response properties. Often it is assumed that single-neuron responses reflect a
      preference for a particular movement or movement variable. It may be further
      assumed that movement is generated by (or at least accompanied by) a growing
      population-level preference for the relevant movement. This view has been
      attractive because it provides a canonical form for the single neuron, a link
      between preparatory and movement activity, a way of interpreting the population
      response, and a platform for designing analyses and couching hypotheses. However,
      this traditional view yields predictions that are at odds with basic features of
      the data. We discuss an alternative simplified model, in which outgoing commands
      are produced by dynamics that generate different output patterns as a function of
      the initial preparatory state. For reaching tasks, we hypothesized simple
      quasioscillatory dynamics because they provide a natural basis set for the
      empirical patterns of muscle activity. The predictions of the dynamical model
      match the data well at both the single-neuron and population levels, and the
      quasioscillatory patterns explain many of the otherwise odd features of the
      neural responses. 

PMID- 25851508
TI  - Pericardial effusion associated with hypothyroidism in an adult female with down
      syndrome.

PMID- 25851507
TI  - Computations in Sensorimotor Learning.
AB  - Our cognitive abilities can only be expressed on the world through our actions.
      Here we review the computations underlying the way that the sensorimotor system
      converts both low-level sensory signals and high-level decisions into action,
      focusing on the behavioral evidence for the theoretical frameworks. We review
      recent work that determines how motor memories underlying sensorimotor learning
      are activated and protected from interference, the role of Bayesian decision
      theory in sensorimotor control including sources of suboptimality, the role of
      risk sensitivity in guiding action, and how rapid motor responses may underlie
      the robustness of the motor system to the vagaries of the world. 

PMID- 25851509
TI  - Isolation and characterization of a new [FeFe]-hydrogenase from Clostridium
      perfringens.
AB  - This paper reports the first characterization of an [FeFe]-hydrogenase from a
      Clostridium perfringens strain previously isolated in our laboratory from a pilot
      scale bio-hydrogen plant that efficiently produces H2 from waste biomasses. On
      the basis of sequence analysis, the enzyme is a monomer formed by four domains
      hosting various iron-sulfur centres involved in electron transfer and the
      catalytic center H-cluster. After recombinant expression in Escherichia coli, the
      purified protein catalyzes H2 evolution at high rate of 1645 +/- 16 s(-1) . The
      optimal conditions for catalysis are in the pH range 6.5-8.0 and at the
      temperature of 50  degrees C. EPR spectroscopy showed that the H-cluster of the
      oxidized enzyme displays a spectrum coherent with the Hox state, whereas the CO
      inhibited enzyme has a spectrum coherent with the Hox -CO state. FTIR
      spectroscopy showed that the purified enzyme is composed of a mixture of redox
      states, with a prevalence of the Hox ; upon reduction with H2 , vibrational modes
      assigned to the Hred state were more abundant, whereas binding of exogenous CO
      resulted in a spectrum assigned to the Hox -CO state. The spectroscopic features
      observed are similar to those of the [FeFe]-hydrogenases class, but relevant
      differences were observed given the different protein environment hosting the H
      cluster. 

PMID- 25851510
TI  - The gene expression signature of anagrelide provides an insight into its
      mechanism of action and uncovers new regulators of megakaryopoiesis.
AB  - BACKGROUND: Anagrelide is a cytoreductive agent used to lower platelet counts in
      essential thrombocythemia. Although the drug has been known to selectively
      inhibit megakaryopoiesis for many years, the molecular mechanism accounting for
      this activity is still unclear. OBJECTIVES AND METHODS: To address this issue we
      have compared the global gene expression profiles of human hematopoietic cells
      treated ex-vivo with and without anagrelide while growing under megakaryocyte
      differentiation conditions, using high-density oligonucleotide microarrays. Gene
      expression data were validated by the quantitative polymerase chain reaction and
      mined to identify functional subsets and regulatory pathways. RESULTS: We
      identified 328 annotated genes differentially regulated by anagrelide, including
      many genes associated with platelet functions and with the control of gene
      transcription. Prominent among the latter was TRIB3, whose expression increased
      in the presence of anagrelide. Pathway analysis revealed that anagrelide up
      regulated genes that are under the control of the transcription factor ATF4, a
      known TRIB3 inducer. Notably, immunoblot analysis demonstrated that anagrelide
      induced the phosphorylation of eIF2alpha, which is an upstream regulator of ATF4,
      and increased ATF4 protein levels. Furthermore, salubrinal, an inhibitor of
      eIF2alpha dephosphorylation, increased the expression of ATF4-regulated genes and
      blocked megakaryocyte growth. CONCLUSIONS: These findings link signaling through
      eIF2alpha/ATF4 to the anti-megakaryopoietic activity of anagrelide and identify
      new potential modulators of megakaryopoiesis.

PMID- 25851512
TI  - Effect of sleep deprivation on the electrophysiological signature of habituation
      to noxious laser stimuli.
AB  - BACKGROUND: Sleep deprivation induces hyperalgesia. However, this pro-nociceptive
      effect is not reflected at the electrophysiological level, since sleep restricted
      subjects show amplitude reduction of Laser-evoked Potentials (LEP). We aimed to
      explore the contribution of habituation to this paradoxical LEP amplitude
      decline. METHODS: We compared LEP's of 12 healthy students (23.2 +/- 1.1 years)
      after habitual sleep (HS) and a night of total sleep deprivation (TSD). Twelve
      repetitive laser stimulus blocks (each comprising twenty stimuli) were applied
      under three attention conditions ('focusing' - 'neutral' - 'distraction'
      condition). Stimulus blocks were split in part 1 (stimulus 1-10) and part 2
      (stimulus 11-20). The contribution of habituation to the TSD-induced LEP
      amplitude decline was studied by calculating the percentage amplitude reduction
      of part 2 as compared to part 1. Individual sleepiness levels were correlated
      with (1) averaged LEP's and (2) the degree of habituation. RESULTS: TSD induced
      hyperalgesia to laser stimuli (p < 0.001). In contrast, depending on the
      attention condition, the P2 amplitude of the N2P2-complex was significantly
      reduced ('focusing': p = 0.004; 'neutral': p = 0.017; distraction: p = 0.71).
      Habituation of the P2 amplitude to radiant heat was increased after TSD
      ('focusing': p = 0.04; 'neutral': p < 0.001; distraction: p = 0.88). TSD had no
      significant effect on N1 amplitudes (p > 0.05). Individual sleepiness correlated
      negatively with averaged P2 amplitudes (p = 0.02), but not with the degree of
      habituation (p = 0.14). CONCLUSION: TSD induces hyperalgesia and results in
      attention-dependent enhanced habituation of the P2 component. Increased
      habituation may--to a substantial degree--explain the TSD-induced LEP-amplitude
      decline. For this article, a commentary is available at the Wiley Online Library.

PMID- 25851511
TI  - The Impact of Left Atrial Surface Area and the Second Generation Cryoballoon on
      Clinical Outcome of Atrial Fibrillation Cryoablation.
AB  - AIMS: In this observational study, we examine the significance of the left atrial
      (LA) surface area and compare the clinical usage of the Arctic Front Advance
      (CBA) versus Arctic Front (CB) cryoballoon with the intent to investigate the
      impact of each in terms of long-term freedom from atrial fibrillation (AF) for
      patients with nonvalvular AF. METHODS: Pulmonary vein isolation (PVI) was
      performed while using a cryoballoon ablation catheter in conjunction with an
      intraluminal circular diagnostic mapping catheter, Achieve. The consecutive
      patients ablated with CBA were matched with patients previously ablated with CB,
      using propensity score matching. The primary endpoint of this observational
      single-center retrospective study was the first observation of electrocardiogram
      documented recurrence of atrial arrhythmias lasting >30 seconds. RESULTS: The
      patient demographic data were similar in the CBA- and CB-group (N = 188 patients
      each group). In all patients in the CBA-group and in 95% of the patients in the
      CB group, acute procedural PVI of all veins was achieved with the single usage of
      a 28-mm cryoballoon. The one-year freedom from atrial arrhythmias was
      significantly better in the CBA- versus the CB-group of patients, 90% versus 64%,
      respectively. During 15-month clinical follow-up in CBA group, patients with LA
      area above 23 cm(2) were more likely to experience recurrence of AF (23%) than
      patients with LA area below 23 cm(2) (7%). CONCLUSIONS: Comparing one-year
      outcomes, the CBA is superior to the CB with regards to maintenance of normal
      sinus rhythm. When using the CBA catheter, an enlarged LA is associated with a
      higher recurrence of arrhythmia.

PMID- 25851514
TI  - Synthesis of non-natural sequence-encoded polymers using phosphoramidite
      chemistry.
AB  - Sequence-defined non-natural polyphosphates were prepared using iterative
      phosphoramidite protocols on a polystyrene solid support. Three monomers were
      used in this work: 2-cyanoethyl (3-dimethoxytrityloxy-propyl)
      diisopropylphosphoramidite (0), 2-cyanoethyl (3-dimethoxytrityloxy-2,2-dimethyl
      propyl) diisopropylphosphoramidite (1), and 2-cyanoethyl (3-dimethoxytrityloxy
      2,2-dipropargyl-propyl) diisopropylphosphoramidite (1'). Phosphoramidite coupling
      steps allowed rapid synthesis of homopolymers and copolymers. In particular, the
      comonomers (0, 1), (0, 1'), and (1, 1') were used to synthesize sequence-encoded
      copolymers. It was found that long encoded sequences could be easily built using
      phosphoramidite chemistry. ESI-HRMS, MALDI-HRMS, NMR, and size exclusion
      chromatography analyses indicated the formation of monodisperse polymers with
      controlled comonomer sequences. The polymers obtained with the comonomers (0, 1')
      and (1, 1') were also modified by copper-catalyzed azide-alkyne cycloaddition
      with a model azide compound, namely 11-azido-3,6,9-trioxaundecan-1-amine. (1)H
      and (13)C NMR analysis evidenced quantitative modification of the alkyne side
      chains of the monodisperse copolymers. Thus, the molecular structure of the
      coding monomer units can be easily varied after polymerization. Altogether, the
      present results open up interesting avenues for the design of information
      containing macromolecules. 

PMID- 25851513
TI  - Mathematical Models to Explore Potential Effects of Supersaturation and
      Precipitation on Oral Bioavailability of Poorly Soluble Drugs.
AB  - Poorly soluble drugs are increasingly formulated into supersaturating drug
      delivery systems which may precipitate during oral delivery. The link between in
      vitro drug concentration profiles and oral bioavailability is under intense
      investigation. The objective of the present work was to develop closed-form
      analytical solutions that relate in vitro concentration profiles to the amount of
      drug absorbed using several alternate assumptions and only six parameters. Three
      parameters define the key features of the in vitro drug concentration-time
      profile. An additional three parameters focus on physiological parameters.
      Absorption models were developed based on alternate assumptions; the drug
      concentration in the intestinal fluid: (1) peaks at the same time and
      concentration as in vitro, (2) peaks at the same time as in vitro, or (3) reaches
      the same peak concentration as in vitro. The three assumptions provide very
      different calculated values of bioavailability. Using Case 2 assumptions,
      bioavailability enhancement was found to be less than proportional to in silico
      examples of dissolution enhancement. Case 3 assumptions lead to bioavailability
      enhancements that are more than proportional to dissolution enhancements. Using
      Case 1 predicts drug absorption amounts that fall in between Case 2 and 3. The
      equations developed based on the alternate assumptions can be used to quickly
      evaluate the potential improvement in bioavailability due to intentional
      alteration of the in vitro drug concentration vs. time curve by reformulation.
      These equations may be useful in making decisions as to whether reformulation is
      expected to provide sufficient bioavailability enhancement to justify the effort.

PMID- 25851515
TI  - A Force to Be Reckoned With: A Review of Synthetic Microswimmers Powered by
      Ultrasound.
AB  - Synthetic microswimmers are a class of artificial nano- or microscale particle
      capable of converting external energy into motion. They are similar to natural
      microswimmers such as bacteria in behavior and are, therefore, of great interest
      to the study of active matter. Additionally, microswimmers show promise in
      applications ranging from bioanalytics and environmental monitoring to particle
      separation and drug delivery. However, since their sizes are on the nano
      /microscale and their speeds are in the MUm s(-1) range, they fall into a low
      Reynolds number regime where viscosity dominates. Therefore, new propulsion
      schemes are needed for these microswimmers to be able to efficiently move.
      Furthermore, many of the hotly pursued applications call for innovations in the
      next phase of development of biocompatible microswimmers. In this review, the
      latest developments of microswimmers powered by ultrasound are presented.
      Ultrasound, especially at MHz frequencies, does little harm to biological samples
      and provides an advantageous and well-controlled means to efficiently power
      microswimmers. By critically reviewing the recent progress in this research
      field, an introduction of how ultrasound propels colloidal particles into
      autonomous motion is presented, as well as how this propulsion can be used to
      achieve preliminary but promising applications.

PMID- 25851516
TI  - Purification and characterization of a trypsin inhibitor from the seeds of
      Artocarpus heterophyllus Lam.
AB  - A proteinaceous inhibitor against trypsin was isolated from the seeds of
      Artocarpus heterophyllus Lam. by successive ammonium sulfate precipitation, ion
      exchange, and gel-filtration chromatography. The trypsin inhibitor, named as
      AHLTI (A. heterophyllus Lam. trypsin inhibitor), consisted of a single
      polypeptide chain with a molecular weight of 28.5 kDa, which was confirmed by
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis and gel-filtration
      chromatography. The N-terminal sequence of AHLTI was DEPPSELDAS, which showed no
      similarity to other known trypsin inhibitor sequence. AHLTI completely inhibited
      bovine trypsin at a molar ratio of 1:2 (AHLTI:trypsin) analyzed by native
      polyacrylamide gel electrophoresis, inhibition activity assay, and gel-filtration
      chromatography. Moreover, kinetic enzymatic studies were carried out to
      understand the inhibition mechanism of AHLTI against trypsin. Results showed that
      AHLTI was a competitive inhibitor with an equilibrium dissociation constant (Ki)
      of 3.7 * 10(-8) M. However, AHLTI showed weak inhibitory activity toward
      chymotrypsin and elastase. AHLTI was stable over a broad range of pH 4-8 and
      temperature 20-80 degrees C. The reduction agent, dithiothreitol, had no obvious
      effect on AHLTI. The trypsin inhibition assays of AHLTI toward digestive enzymes
      from insect pest guts in vitro demonstrated that AHLTI was effective against
      enzymes from Locusta migratoria manilensis (Meyen). These results suggested that
      AHLTI might be a novel trypsin inhibitor from A. heterophyllus Lam. belonging to
      Kunitz family, and play an important role in protecting from insect pest. 

PMID- 25851517
TI  - Zebrafish phosvitin is an antioxidant with non-cytotoxic activity.
AB  - Antioxidants, or anti-oxidant agents, have attracted a great deal of attention in
      recent years because of their roles in prevention of chronic diseases and
      utilization as preservatives in food and cosmetics. In this study, we clearly
      demonstrated that zebrafish recombinant phosvitin (rPv) is an antioxidant agent
      capable of inhibiting the oxidation of the linoleic acid, and scavenging the 2,2
      diphenyl-1-picrylhydrazyl radical. We also showed that zebrafish rPv is a
      cellular antioxidant capable of protecting radical-mediated oxidation of cellular
      biomolecules. Importantly, zebrafish rPv is non-cytotoxic to murine macrophage
      RAW264.7 cells. It is the first report that showed the antioxidant activities of
      Pv in fishes, suggesting that zebrafish Pv can be an important antioxidant, which
      can be used as preservatives in food and cosmetics and even as supplementary
      mediator in different diseased states. 

PMID- 25851520
TI  - Editorial comment on paper by Naguib, et al. 'A single-center strategy to
      minimize blood transfusion in neonates and children undergoing cardiac surgery'.

PMID- 25851521
TI  - What is the condition of education in Pediatric Anesthesiology?

PMID- 25851522
TI  - Reply to Dr. Haydar regarding his comment: caudal clonidine and apnea risk.

PMID- 25851523
TI  - Fluid resuscitation for toddlers and young children.

PMID- 25851524
TI  - Carbon monoxide has antinociceptive effects in rodent models of pain.

PMID- 25851525
TI  - Spontaneous fungal peritonitis: a devastating complication of cirrhosis.
AB  - Spontaneous bacterial peritonitis is a well-known complication of cirrhosis;
      however, spontaneous fungal peritonitis (SFP) is less well-recognised and
      described. Our objective was to determine the clinical characteristics, treatment
      outcomes and factors associated with death among patients with SFP. We performed
      a retrospective cohort study using the primary outcome of all-cause mortality at
      28 days. Twenty-five patients were included; Candida species were the causative
      pathogen in all cases. At the onset of SFP, patients were critically ill, median
      APACHE II and MELD scores were 22 and 30.3, respectively. The 28-day mortality
      rate was 56%; six patients died prior to culture positivity. Among the remaining
      patients, there were no differences in rates of death by treatment regimen (P =
      0.55). APACHE II score at the onset of SFP was an independent predictor of death
      (OR = 1.46, 95% CI = 1.02-2.08, P = 0.04). In conclusion, SFP develops among
      critically ill patients with cirrhosis and is associated with high rates of
      death. Directed antifungal therapy did not improve patient outcomes. Future
      studies assessing the benefit of early or pre-emptive antifungal therapy are
      warranted.

PMID- 25851526
TI  - The effect of dietary arachidonic acid (ARA) on growth performance, fatty acid
      composition and expression of ARA metabolism-related genes in larval half-smooth
      tongue sole (Cynoglossus semilaevis).
AB  - The present study was conducted to investigate the effects of dietary arachidonic
      acid (ARA) on growth performance, fatty acid composition and ARA metabolism
      related gene expression in larval half-smooth tongue sole (Cynoglossus
      semilaevis). Larvae (35 d after hatching, 54 (SEM 1) mg) were fed diets with
      graded concentrations of ARA (0.01, 0.39, 0.70, 1.07, 1.42 and 2.86 % dry weight)
      five times per d to apparent satiation for 30 d. Results showed that increased
      dietary ARA concentration caused a significant non-linear rise to a plateau in
      survival rate, final body weight and thermal growth coefficient, and the maximum
      values occurred with the 1.42 % ARA treatment. As dietary ARA increased to 1.07
      or 1.42 %, activities of trypsin, leucine aminopeptidase and alkaline phosphatase
      levels increased, but they decreased with higher ARA concentrations. The fatty
      acid composition of tongue sole larvae was almost well correlated with their
      dietary fatty acid profiles, and the EPA content of the larvae decreased with
      increasing dietary ARA. Meanwhile, the partial sequences of COX-1a (cyclo
      oxygenase-1a), COX-1b (cyclo-oxygenase-1b), COX-2 (cyclo-oxygenase-2), 5-LOX (5
      lipoxygenase) and CYP2J6-like (cytochrome P450 2J6-like) were also obtained. Both
      COX-2 and 5-LOX mRNA expression levels significantly increased to a plateau in an
      'L'-shaped manner as dietary ARA increased to 1.07 or 1.42 %, but no significant
      differences were found in the gene expression of COX-1a, COX-1b or CYP2J6-like.
      These results suggest that 1.07-1.42 % dietary ARA was beneficial to the growth
      performance of larval tongue sole, and the regulation of dietary ARA on the
      growth performance of larvae was probably involved in altering the mRNA
      expression of COX-2 and 5-LOX.

PMID- 25851527
TI  - Distinct higher-order alpha-synuclein oligomers induce intracellular aggregation.
AB  - Misfolding and aggregation of alpha-synuclein (alpha-syn) into Lewy bodies is
      associated with a range of neurological disorders, including Parkinson's disease
      (PD). The cell-to-cell transmission of alpha-syn pathology has been linked to
      soluble amyloid oligomer populations that precede Lewy body formation. Oligomers
      produced in vitro under certain conditions have been demonstrated to induce
      intracellular aggregation in cell culture models. In the present study, we
      characterize, by ESI-ion mobility spectrometry (IMS)-MS, a specific population of
      alpha-syn oligomers. These MS-compatible oligomers were compared with oligomers
      with known seeding and pore-forming capabilities and were shown to have the
      ability to induce intracellular aggregation. Each oligomer type was shown to have
      distinct epitope profiles that correlated with their toxic gain-of-function.
      Structurally, the MS compatible oligomers populated a range of species from
      dimers through to hexamers. Lower-order oligomers were structurally diverse and
      consistent with unstructured assemblies. Higher-order oligomers were shown to be
      compact with ring-like structures. The observation of this compact state may
      explain how this natively disordered protein is able to transfer pathology from
      cell to cell and avoid degradation by cellular proteases. 

PMID- 25851528
TI  - Body language: The interplay between positional behavior and gestural signaling
      in the genus Pan and its implications for language evolution.
AB  - OBJECTIVES: The gestural repertoires of bonobos and chimpanzees are well
      documented, but the relationship between gestural signaling and positional
      behavior (i.e., body postures and locomotion) has yet to be explored. Given that
      one theory for language evolution attributes the emergence of increased gestural
      communication to habitual bipedality, this relationship is important to
      investigate. MATERIALS AND METHODS: In this study, we examined the interplay
      between gestures, body postures, and locomotion in four captive groups of bonobos
      and chimpanzees using ad libitum and focal video data. RESULTS: We recorded 43
      distinct manual (involving upper limbs and/or hands) and bodily (involving
      postures, locomotion, head, lower limbs, or feet) gestures. In both species,
      actors used manual and bodily gestures significantly more when recipients were
      attentive to them, suggesting these movements are intentionally communicative.
      Adults of both species spent less than 1.0% of their observation time in bipedal
      postures or locomotion, yet 14.0% of all bonobo gestures and 14.7% of all
      chimpanzee gestures were produced when subjects were engaged in bipedal postures
      or locomotion. Among both bonobo groups and one chimpanzee group, these were
      mainly manual gestures produced by infants and juvenile females. Among the other
      chimpanzee group, however, these were mainly bodily gestures produced by adult
      males in which bipedal posture and locomotion were incorporated into
      communicative displays. DISCUSSION: Overall, our findings reveal that bipedality
      did not prompt an increase in manual gesturing in these study groups. Rather,
      body postures and locomotion are intimately tied to many gestures and certain
      modes of locomotion can be used as gestures themselves.

PMID- 25851530
TI  - Fast preparation of a highly efficient organic monolith via photo-initiated thiol
      ene click polymerization for capillary liquid chromatography.
AB  - A novel organic monolith was firstly prepared in a UV-transparent fused-silica
      capillary by a single-step approach via photo-initiated thiol-ene click
      polymerization reaction of 1,2,4-trivinylcyclohexane (TVCH) and pentaerythriol
      tetra(3-mercaptopropionate) (4SH) within 10min. The effects of both composition
      of prepolymerization solution and polymerization time on the morphology and
      permeability of monolithic column were investigated in detail. Then, the optimal
      condition was acquired to fabricate a homogeneous and permeable organic monolith.
      The chemical groups of the monolithic column were confirmed by Fourier transform
      infrared spectroscopy (FT-IR). The SEM graphs showed the organic monolith
      possessed a uniform porous structure, which promotes the highest column
      efficiency of ~133,000 plates per meter for alkylbenzenes at the linear velocity
      of 0.65mm/s in reversed-phase liquid chromatography. Finally, the organic
      monolithic column was further applied for separation of basic compounds,
      pesticides and EPA610, indicating satisfactory separation ability. 

PMID- 25851531
TI  - Cerebrolysin reverses hippocampal neural atrophy in a mice model of diabetes
      mellitus type 1.
AB  - The animal model of streptozotocin-induced diabetes mellitus type 1 (DM1) is used
      to study neuronal and behavioral changes produced by an increase in blood-glucose
      levels. Our previous report showed that chronic streptozotocin administration
      induced atrophy of dendritic morphology of pyramidal neurons of the CA1 dorsal
      hippocampus. In addition, we showed that Cerebrolysin (Cbl), a neurotrophic
      peptide mixture, reduces the dendritic atrophy in animal models of aging. This
      study aimed to determine whether Cbl was capable of reducing behavioral and
      neuronal alterations, after 6 weeks of hyperglycemia in mice (streptozotocin
      induced DM1). The levels of glucose in the blood were evaluated before and after
      streptozotocin administration and only animals with more than 240 mg/dL of blood
      levels of glucose were used. After streptozotocin treatment, the mice received 6
      weeks of Cbl, locomotor activity was measured and dendritic morphological changes
      were evaluated using Golgi-Cox stain procedure, and analyzed by the Sholl method.
      In mice treated with streptozotocin there was a clear reduction in the dendritic
      length of pyramidal neurons of the CA1 and granular cells of the dental gyrus of
      the dorsal hippocampus. Interestingly, Cbl reversed the morphological changes
      induced by streptozotocin. Our results extend the list of abnormal morphological
      changes detected in this model of DM, and support the possibility that Cbl may
      have beneficial effects in the management of brain alterations induced by DM.

PMID- 25851532
TI  - Extracellular Streptomyces lividans vesicles: composition, biogenesis and
      antimicrobial activity.
AB  - We selected Streptomyces lividans to elucidate firstly the biogenesis and
      antimicrobial activities of extracellular vesicles that a filamentous and highly
      differentiated Gram-positive bacterium produces. Vesicle types range in diameter
      from 110 to 230 nm and 20 to 60 nm, respectively; they assemble to clusters, and
      contain lipids and phospholipids allowing their in situ imaging by specific
      fluorescent dyes. The presence of the identified secondary metabolite
      undecylprodigiosin provokes red fluorescence of a portion of the heterogeneous
      vesicle populations facilitating in vivo monitoring. Protuberances containing
      vesicles generate at tips, and alongside of substrate hyphae, and enumerate
      during late vegetative growth to droplet-like exudates. Owing to in situ imaging
      in the presence and absence of a green fluorescent vancomycin derivative, we
      conclude that protuberances comprising vesicles arise at sites with enhanced
      levels of peptidoglycan subunits [pentapeptide of lipid II (C55)-linked
      disaccharides], and reduced levels of polymerized and cross-linked peptidoglycan
      within hyphae. These sites correlate with enhanced levels of anionic
      phospholipids and lipids. Vesicles provoke pronounced damages of Aspergillus
      proliferans, Verticillium dahliae and induced clumping and distortion of
      Escherichia coli. These harmful effects are likely attributable to the action of
      the identified vesicular compounds including different enzyme types, components
      of signal transduction cascades and undecylprodigiosin. Based on our pioneering
      findings, we highlight novel clues with environmental implications and
      application potential.

PMID- 25851533
TI  - Detecting outlying trials in network meta-analysis.
AB  - Network meta-analysis (NMA) expands the scope of a conventional pairwise meta
      analysis to simultaneously handle multiple treatment comparisons. However, some
      trials may appear to deviate markedly from the others and thus be inappropriate
      to be synthesized in the NMA. In addition, the inclusion of these trials in
      evidence synthesis may lead to bias in estimation. We call such trials trial
      level outliers. To the best of our knowledge, while heterogeneity and
      inconsistency in NMA have been extensively discussed and well addressed, few
      previous papers have considered the proper detection and handling of trial-level
      outliers. In this paper, we propose several Bayesian outlier detection measures,
      which are then applied to a diabetes data set. Simulation studies comparing our
      approaches in both arm-based and contrast-based model settings are provided in
      two supporting appendices.

PMID- 25851534
TI  - Factors influencing delivered mean airway pressure during nasal CPAP with the RAM
      cannula.
AB  - OBJECTIVE: To measure mean airway pressure (MAP) delivered through the RAM
      Cannula(r) when used with a ventilator in CPAP mode as a function of percent
      nares occlusion in a simulated nasal interface/test lung model and to compare the
      results to MAPs using a nasal continuous positive airway pressure (NCPAP)
      interface with nares fully occluded. STUDY DESIGN: An artificial airway model was
      connected to a spontaneous breathing lung model in which MAP was measured at set
      NCPAP levels between 4 and 8 cmH2 O provided by a Drager Evita XL(r) ventilator
      and delivered through three sizes of RAM cannulae. Measurements were performed
      with varying leakage at the nasal interface by decreasing occlusion from 100% to
      29%, half-way prong insertion, and simulated mouth leakage. Comparison
      measurements were made using the Drager BabyFlow(r) NCPAP interface with a full
      nasal seal. RESULTS: With simulated mouth closed, the Drager interface delivered
      MAPs within 0.5 cmH2 O of set CPAP levels. For the RAM cannula, with 60-80% nares
      occlusion, overall delivered MAPs were 60 +/- 17% less than set CPAP levels (P <
      0.001). Further, MAP decreased progressively with decreasing percent nares
      occlusion. The simulated open mouth condition resulted in significantly lower
      MAPs to <1.7 cmH2 O. The one-half prong insertion depth condition, with closed
      mouth, yielded MAPs approximately 35 +/- 9% less than full insertion pressures (P
      < 0.001). CONCLUSIONS: In our bench tests, the RAM interface connected to a
      ventilator in NCPAP mode failed to deliver set CPAP levels when applied using the
      manufacturer recommended 60-80% nares occlusion, even with closed mouth and full
      nasal prong insertion conditions.

PMID- 25851535
TI  - ADAP and SKAP55 deficiency suppresses PD-1 expression in CD8+ cytotoxic T
      lymphocytes for enhanced anti-tumor immunotherapy.
AB  - PD-1 negatively regulates CD8(+) cytotoxic T lymphocytes (CTL) cytotoxicity and
      anti-tumor immunity. However, it is not fully understood how PD-1 expression on
      CD8(+) CTL is regulated during anti-tumor immunotherapy. In this study, we have
      identified that the ADAP-SKAP55 signaling module reduced CD8(+) CTL cytotoxicity
      and enhanced PD-1 expression in a Fyn-, Ca(2+)-, and NFATc1-dependent manner. In
      DC vaccine-based tumor prevention and therapeutic models, knockout of SKAP55 or
      ADAP showed a heightened protection from tumor formation or metastases in mice
      and reduced PD-1 expression in CD8(+) effector cells. Interestingly, CTLA-4
      levels and the percentages of tumor infiltrating CD4(+)Foxp3(+) Tregs remained
      unchanged. Furthermore, adoptive transfer of SKAP55-deficient or ADAP-deficient
      CD8(+) CTLs significantly blocked tumor growth and increased anti-tumor immunity.
      Pretreatment of wild-type CD8(+) CTLs with the NFATc1 inhibitor CsA could also
      downregulate PD-1 expression and enhance anti-tumor therapeutic efficacy.
      Together, we propose that targeting the unrecognized ADAP-SKAP55-NFATc1-PD-1
      pathway might increase efficacy of anti-tumor immunotherapy. 

PMID- 25851536
TI  - New insights into the pathology of pulmonary hypertension: implication of the miR
      210/ISCU1/2/Fe-S axis.
AB  - Elevated pulmonary arterial pressure in patients with pulmonary hypertension (PH)
      is mainly caused by increased pulmonary vascular resistance (PVR), due primarily
      to sustained pulmonary vasoconstriction and excessive pulmonary vascular
      remodeling. According to the current classification, PH has been classified into
      five categories based on etiology (Simonneau et al, 2013). Among them, group 1 or
      pulmonary arterial hypertension (PAH) is a rare but progressive and deadly
      disease affecting ~1-10 per 1 million people. Despite expanding treatment options
      to ameliorate patients' symptoms, PAH remains a devastating disease with a poor
      long-term prognosis.

PMID- 25851537
TI  - Regulation of hematogenous tumor metastasis by acid sphingomyelinase.
AB  - Metastatic dissemination of cancer cells is the ultimate hallmark of malignancy
      and accounts for approximately 90% of human cancer deaths. We investigated the
      role of acid sphingomyelinase (Asm) in the hematogenous metastasis of melanoma
      cells. Intravenous injection of B16F10 melanoma cells into wild-type mice
      resulted in multiple lung metastases, while Asm-deficient mice (Smpd1(-/-) mice)
      were protected from pulmonary tumor spread. Transplanting wild-type platelets
      into Asm-deficient mice reinstated tumor metastasis. Likewise, Asm-deficient mice
      were protected from hematogenous MT/ret melanoma metastasis to the spleen in a
      mouse model of spontaneous tumor metastasis. Human and mouse melanoma cells
      triggered activation and release of platelet secretory Asm, in turn leading to
      ceramide formation, clustering, and activation of alpha5beta1 integrins on
      melanoma cells finally leading to adhesion of the tumor cells. Clustering of
      integrins by applying purified Asm or C16 ceramide to B16F10 melanoma cells
      before intravenous injection restored trapping of tumor cells in the lung in Asm
      deficient mice. This effect was revertable by arginine-glycine-aspartic acid
      peptides, which are known inhibitors of integrins, and by antibodies neutralizing
      beta1 integrins. These findings indicate that melanoma cells employ platelet
      derived Asm for adhesion and metastasis. 

PMID- 25851538
TI  - Vasculotide reduces endothelial permeability and tumor cell extravasation in the
      absence of binding to or agonistic activation of Tie2.
AB  - Angiopoietin-1 (Ang1) activation of Tie2 receptors on endothelial cells (ECs)
      reduces adhesion by tumor cells (TCs) and limits junctional permeability to TC
      diapedesis. We hypothesized that systemic therapy with Vasculotide (VT)-a
      purported Ang1 mimetic, Tie2 agonist-can reduce the extravasation of potentially
      metastatic circulating TCs by similarly stabilizing the host vasculature. In
      vitro, VT and Ang1 treatments impeded endothelial hypermeability and the
      transendothelial migration of MDA-MB-231?LM2-4 (breast), HT29 (colon), or SN12
      (renal) cancer cells to varying degrees. In mice, VT treatment inhibited the
      transit of TCs through the pulmonary endothelium, but not the hepatic or
      lymphatic endothelium. In the in vivo LM2-4 model, VT monotherapy had no effect
      on primary tumors, but significantly delayed distant metastatic dissemination to
      the lungs. In the post-surgical adjuvant treatment setting, VT therapeutically
      complemented sunitinib therapy, an anti-angiogenic tyrosine kinase inhibitor
      which limited the local growth of residual disease. Unexpectedly, detailed
      investigations into the putative mechanism of action of VT revealed no evidence
      of Tie2 agonism or Tie2 binding; alternative mechanisms have yet to be
      determined. 

PMID- 25851539
TI  - Usefulness of core needle biopsy for thyroid nodules with macrocalcifications:
      comparison with fine-needle aspiration.
AB  - BACKGROUND: This study was performed to determine the benefits of core needle
      biopsy (CNB), as compared with fine-needle aspiration (FNA), for the diagnosis of
      thyroid nodules with macrocalcifications. MATERIALS AND METHODS: The
      institutional review board approved this retrospective study, and informed
      consent was waived. From February 2010 to March 2012, the study included 147
      thyroid nodules with macrocalcification of 145 consecutive patients who underwent
      simultaneous FNA and CNB for each nodule. Diagnostic accuracy and inconclusive
      diagnoses, including nondiagnostic reading and atypia of undetermined
      significance or follicular lesion of undetermined significance reading were
      compared among FNA, CNB, and a combination of FNA and CNB (FNA/CNB) using
      McNemar's test; the benefits of CNB were calculated. RESULTS: Compared to FNA,
      CNB and FNA/CNB showed fewer inconclusive diagnoses (FNA vs. CNB: 62/147 [42.2%]
      vs. 14/147 [9.5%], p<0.001; FNA vs. FNA/CNB: 62/147 [42.2%] vs. 14/147 [9.5%],
      p<0.001), resulting in the avoidance of repeat FNA or diagnostic surgery in 48 of
      62 patients (77.4%, respectively in CNB and FNA/CNB) who would have undergone
      these procedures if only FNA was performed. Compared to FNA, FNA/CNB showed
      higher sensitivity and accuracy (sensitivity: 23/32 [71.9%] vs. 31/32 [96.9%],
      p=0.008; accuracy: 77/86 [89.5%] vs. 85/86 [98.8%], p=0.008), resulting in
      avoidance of delayed surgery in eight of nine patients (88.9%) with thyroid
      cancer in whom the surgery would have been missed if FNA only had been performed.
      CONCLUSION: In the workup of thyroid nodules with macrocalcification, compared
      with FNA alone, FNA/CNB decreases inconclusive diagnoses and increases
      sensitivity, thereby reducing repeated FNA procedures, diagnostic surgeries, and
      delayed therapeutic surgeries.

PMID- 25851541
TI  - Nonsuppurative Nodular Panniculitis of the Breast.

PMID- 25851542
TI  - Glycated albumin is more closely correlated with coronary artery disease than 1,5
      anhydroglucitol and glycated hemoglobin A1c.
AB  - BACKGROUND: The aim of this study was to investigate the associations of two
      nontraditional glycemic markers, glycated albumin (GA) and 1,5-anhydroglucitol
      (1,5-AG), as well as glycated hemoglobin A1c (HbA1c) with coronary artery disease
      (CAD). METHODS: In total, 272 subjects (178 men and 94 postmenopausal women) were
      enrolled in this study. All of them underwent coronary angiography which was used
      to diagnose CAD. The severity of coronary artery stenosis was assessed by the
      coronary stenosis index (CSI). GA and 1,5-AG were assayed using the enzymatic
      method, and HbA1c was detected by high-pressure liquid chromatography. RESULTS:
      The HbA1c and GA levels were significantly higher in CAD group than those in non
      CAD group (both P < 0.01). While the 1,5-AG level was significantly lower in CAD
      group than that in non-CAD group (P < 0.05). After adjustment for traditional
      risk factors of CAD, HbA1c, 1,5-AG, and GA, multivariate logistic regression
      analysis showed that GA was an independent risk factor for CAD (odds ratio =
      1.143, 95% confidence interval: 1.048-1.247, P = 0.002). With CSI as a dependent
      variable, multiple stepwise regression analysis demonstrated an independent
      positive correlation between GA and CSI (standardized beta = 0.184, P = 0.003),
      beyond gender, age, and lipid-lowering therapy, after adjustment for traditional
      risk factors of CAD, HbA1c, 1,5-AG, and GA. CONCLUSIONS: GA was more closely
      correlated with CAD than HbA1c and 1,5-AG in a Chinese population with high risk
      of CAD.

PMID- 25851543
TI  - Rigid multibody simulation of a helix-like structure: the dynamics of bacterial
      adhesion pili.
AB  - We present a coarse-grained rigid multibody model of a subunit assembled helix
      like polymer, e.g., adhesion pili expressed by bacteria, that is capable of
      describing the polymer's force-extension response. With building blocks
      representing individual subunits, the model appropriately describes the complex
      behavior of pili expressed by the gram-negative uropathogenic Escherichia coli
      bacteria under the action of an external force. Numerical simulations show that
      the dynamics of the model, which include the effects of both unwinding and
      rewinding, are in good quantitative agreement with the characteristic force
      extension response as observed experimentally for type 1 and P pili. By tuning
      the model, it is also possible to reproduce the force-extension response in the
      presence of anti-shaft antibodies, which dramatically changes the mechanical
      properties. Thus, the model and results in this work give enhanced understanding
      of how a pilus unwinds under the action of external forces and provide a new
      perspective of the complex bacterial adhesion processes. 

PMID- 25851544
TI  - Clinical-scale purification of pluripotent stem cell derivatives for cell-based
      therapies.
AB  - Human pluripotent stem cells (hPSCs) have the potential to revolutionize cell
      replacement therapies because of their ability to self renew and differentiate
      into nearly every cell type in the body. However, safety concerns have delayed
      the clinical translation of this technology. One cause for this is the capacity
      that hPSCs have to generate tumors after transplantation. Because of the
      challenges associated with achieving complete differentiation into clinically
      relevant cell types, the development of safe and efficient strategies for
      purifying committed cells is essential for advancing hPSC-based therapies.
      Several purification strategies have now succeeded in generating non-tumorigenic
      and homogeneous cell-populations. These techniques typically enrich for cells by
      either depleting early committed populations from teratoma-initiating hPSCs or by
      positively selecting cells after differentiation. Here we review the working
      principles behind separation methods that have facilitated the safe and
      controlled application of hPSC-derived cells in laboratory settings and pre
      clinical research. We underscore the need for improving and integrating
      purification strategies within differentiation protocols in order to unlock the
      therapeutic potential of hPSCs. 

PMID- 25851545
TI  - Trans-aortic endoscopic ventricular thrombectomy in a patient with HIT and
      concomitant Aortic and ventricular thromboses.
AB  - Dual aortic and ventricular thrombi are rare following myocardial infraction. We
      report the case of a 56-year-old man who initially denied primary percutaneous
      coronary intervention as a result of psychological phobia. Initial
      pharmacological management by thrombolysis and heparin was followed by multiple
      arterial thromboses including those of the left ventricle and right iliac artery
      with a subsequent diagnosis of heparin-induced thrombocytopaenia. Ensuing
      surgical management revealed the unanticipated finding of an additional aortic
      sinus thrombosis that was excised. The left ventricular thrombus was removed
      endoscopically to prevent ventricular incisions. This case emphasizes the
      technical advantages of video-endoscopic management of intracardiac thrombi and
      highlights the unexpected nature of multiple thromboses associated with heparin
      induced thrombocytopaenia. 

PMID- 25851546
TI  - Uncommon non-Hodgkin lymphomas of childhood: pathological diagnosis, clinical
      features and treatment approaches.
AB  - We provide a review of the pathological and clinical features for uncommon B-cell
      and T-cell lymphomas of childhood with a specific focus on advances in treatment
      approaches and outcomes. There is clearly a need for prospective investigation of
      both the clinical and biological features of the uncommon non-Hodgkin lymphoma
      subtypes in childhood. These results should lead to more uniform and more
      effective treatment approaches. 

PMID- 25851547
TI  - Association between mental disorders and physical diseases in adolescents from a
      nationally representative cohort.
AB  - OBJECTIVE: Pediatric health care and research focus mostly on single morbidities,
      although the single-disease framework has been challenged. The main objective was
      to estimate associations between childhood mental disorders and physical
      diseases. METHODS: This study is based on weighted data (n = 6482) from the
      National Comorbidity Survey Replication Adolescent Supplement (age, 13-18 years).
      Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition lifetime
      mental disorders were assessed using the fully structured World Health
      Organization Composite International Diagnostic Interview, complemented by parent
      report. Lifetime medical conditions and doctor-diagnosed diseases were assessed
      by adolescent self-report. RESULTS: Of 6469 participants, 2137 (35.33%) reported
      at least one mental disorder and one physical disease. The most substantial
      associations included those between affective disorders and diseases of the
      digestive system (odds ratio [OR] = 3.46, 95% confidence interval [CI] = 2.28
      5.24), anxiety disorders and arthritis (OR = 2.27, CI = 1.34-3.85), anxiety
      disorders and heart diseases (OR = 2.41, CI = 1.56-3.73), anxiety disorders and
      diseases of the digestive system (OR = 2.18, CI = 1.35-3.53), and eating
      disorders and epilepsy/seizures (OR = 5.45, CI = 1.57-18.87). Sociodemographic
      factors did not account for the association between mental disorders and physical
      diseases. CONCLUSIONS: Findings suggest that mental disorders and physical
      diseases often co-occur in childhood. This association is a major public health
      challenge, and the child health system needs additional strategies in patient
      centered care, research, medical education, health policy, and economics to
      develop well-coordinated interdisciplinary approaches linking mental and physical
      care in children.

PMID- 25851548
TI  - Use of CSF alpha-synuclein in the differential diagnosis between Alzheimer's
      disease and other neurodegenerative disorders.
AB  - BACKGROUND: The etiology and pathogenesis of neurodegenerative disorders has yet
      to be elucidated, so their differential diagnosis is a challenge. This is
      especially true in differentiating Alzheimer's disease (AD), dementia with Lewy
      bodies (DLB), Parkinson disease (PD), and multiple system atrophy (MSA). METHODS:
      A total of 11 eligible articles were identified by search of electronic databases
      including PubMed, Springer Link, Elsevier, and the Cochrane Library, up to June
      2014. In meta-analyses, standardized mean differences (SMD), with 95% confidence
      intervals (CI), comparing cerebrospinal fluid (CSF) measures of alpha-synuclein
      between the above conditions were calculated using random-effects models.
      RESULTS: CSF alpha-synuclein concentrations were significantly higher in AD
      compared to DLB [SMD: 0.32, 95% CI: (0.02, 0.62), z = 2.07, P = 0.038]; PD [SMD:
      0.87, 95% CI: (0.15, 1.58), z = 2.38, P = 0.017]; or MSA [SMD: 1.14, 95% CI:
      (0.15, 2.14), z = 2.25, P = 0.025]. However, no significant difference was found
      between patients with AD and neurological cognitively normal controls [SMD: 0.02,
      95% CI: (-0.21, 0.24), z = 0.13, P = 0.894]. CONCLUSIONS: Results of these meta
      analysis suggest that quantification of CSF alpha-synuclein could help
      distinguish AD from other neurodegenerative disorders such as DLB, PD, or MSA.

PMID- 25851549
TI  - Scorpion-related cardiomyopathy: Clinical characteristics, pathophysiology, and
      treatment.
AB  - CONTEXT: Scorpion envenomation is a threat to more than 2 billion people
      worldwide with an annual sting number exceeding one million. Acute heart failure
      presenting as cardiogenic shock or pulmonary edema, or both is the most severe
      presentation of scorpion envenomation accounting for 0.27% lethality rate.
      OBJECTIVE: The purpose of this review is to characterize the scorpion-related
      cardiomyopathy, clarify its pathophysiological mechanisms, and describe
      potentially useful treatments in this particular context. METHODS: We searched
      major databases on observational or interventional studies (whether clinical or
      experimental) on the cardiorespiratory consequences of scorpion envenomation and
      their treatment. No limit of age or language was imposed. A critical appraisal of
      the literature was conducted in order to provide a pathophysiological scheme that
      reconciles reported patterns of cardiovascular toxicity and hypotheses and
      assumptions made so far. RESULTS: Early cardiovascular dysfunction is related to
      the so-called "vascular phase" of scorpion envenomation, which is related to a
      profound catecholamine-related vasoconstriction leading to a sharp increase in
      left ventricular (LV) afterload, thereby impeding LV emptying, and increasing LV
      filling pressure. Following this vascular phase, a myocardial phase occurs,
      characterized by a striking alteration in LV contractility (myocardial stunning),
      low cardiac output, and hypotensive state. The right ventricle involvement is
      symmetric to that of LV with a profound and reversible alteration in right
      ventricular performance. This phase is unique in that it is reversible
      spontaneously or under inotropic treatment. Scorpion myocardiopathy combines the
      features of takotsubo myocardiopathy (or stress myocardiopathy) which is linked
      to a massive release in catecholamines leading to myocardial ischemia through
      coronary vasomotor abnormalities (epicardial coronary spasm and/or increase in
      coronary microvascular resistance). Treatment of pulmonary edema due to scorpion
      envenomation follows the same principles as those applied for the treatment of
      cardiogenic pulmonary edema in general: this begins with oxygen supplementation
      targeting an oxygen saturation of 92% or more, by oxygen mask, continuous
      positive airway pressure, noninvasive ventilation, or conventional mechanical
      ventilation. Dobutamine effectively improves hemodynamic parameters and may
      reduce mortality in severe scorpion envenomation. CONCLUSION: Scorpion
      cardiomyopathy is characterized by a marked and reversible alteration in
      biventricular performance. Supportive treatment relying on ventilatory support
      and dobutamine infusion is a bridge toward recovery in the majority of patients.

PMID- 25851550
TI  - Association of Physician Certification Policy and Quality of Care: Evidence of
      percutaneous coronary intervention certification program in Taiwan.
AB  - OBJECTIVES: The aim of this study was to compare procedural, short-term and two
      year outcomes of percutaneous coronary intervention (PCI) between board-certified
      and non-board certified interventional cardiologists in Taiwan. BACKGROUND: Most
      studies of associations between quality and certification have analyzed
      populations in the Western developed countries. METHODS: This retrospective
      population-based study analyzed 2057 patients who had received PCI in 11
      hospitals in 2007. The outcome measures were procedural, 30-day, and 2-year
      adverse events. RESULTS: Sixty certified physicians performed 1771 PCI procedures
      whereas 84 non-certified physicians performed 286 procedures. Patients treated by
      non-certified physicians had significantly higher rates of in-hospital mortality
      (6.99% vs. 2.82%, respectively; p <= 0.001) and same-stay CABG (1.40% vs. 0.06%,
      respectively; p <= 0.001). The results of multilevel logistic regression and Cox
      multivariate regression indicated that patients treated by non-certified
      physicians also had higher probabilities of in-hospital death (OR=2.92, 95% CI:
      1.20-7.08) and two-year death (hazard ratio, 1.63; 95% confidence interval, 1.18
      2.24). CONCLUSIONS: This is the first study in Asia in investigating the
      association between board certification policy and surgical outcomes, and the
      results confirmed that the board certification policy is also effective for Asian
      population. The policy implications of these findings are discussed.

PMID- 25851551
TI  - Safety testing and operational procedures for self-developed radiofrequency
      coils.
AB  - The development of novel radiofrequency (RF) coils for human ultrahigh-field (>=7
      T), non-proton and body applications is an active field of research in many MR
      groups. Any RF coil must meet the strict requirements for safe application on
      humans with respect to mechanical and electrical safety, as well as the specific
      absorption rate (SAR) limits. For this purpose, regulations such as the
      International Electrotechnical Commission (IEC) standard for medical electrical
      equipment, vendor-suggested test specifications for third party coils and custom
      developed test procedures exist. However, for higher frequencies and shorter
      wavelengths in ultrahigh-field MR, the RF fields may become extremely
      inhomogeneous in biological tissue and the risk of localized areas with elevated
      power deposition increases, which is usually not considered by existing safety
      testing and operational procedures. In addition, important aspects, such as risk
      analysis and comprehensive electrical performance and safety tests, are often
      neglected. In this article, we describe the guidelines used in our institution
      for electrical and mechanical safety tests, SAR simulation and verification, risk
      analysis and operational procedures, including coil documentation, user training
      and regular quality assurance testing, which help to recognize and eliminate
      safety issues during coil design and operation. Although the procedure is
      generally applicable to all field strengths, specific requirements with regard to
      SAR-related safety and electrical performance at ultrahigh-field are considered.
      The protocol describes an internal procedure and does not reflect consensus among
      a large number of research groups, but rather aims to stimulate further
      discussion related to minimum coil safety standards. Furthermore, it may help
      other research groups to establish their own procedures. Copyright (c) 2015 John
      Wiley & Sons, Ltd.

PMID- 25851552
TI  - Vaginal Yolk Sac Tumor in an Infant: A Case Report and Literature Review of the
      Last 30 Years.
AB  - Vaginal yolk sac tumor is a rare malignant germ-cell tumor occurring most
      commonly in young girls. The treatment has evolved over the last 3 decades from
      radical surgery to conservative surgery with chemotherapy to chemotherapy alone.
      Here we present a case of a 6-month-old girl successfully treated with upfront
      surgery followed by chemotherapy. We include a literature review of studies on
      vaginal yolk sac tumor published in the last 30 years. We discuss the role of
      upfront surgery where possible followed by chemotherapy as a safe alternative to
      chemotherapy alone for the treatment of this rare malignancy. 

PMID- 25851553
TI  - ABO Group as a Thrombotic Risk Factor in Children With Acute Lymphoblastic
      Leukemia: A Retrospective Study of 523 Patients.
AB  - Children with acute lymphoblastic leukemia (ALL) are at high risk of thrombotic
      complications, resulting from multiple risk factors (malignancy, chemotherapy,
      central venous access devices, and inherent host characteristics). Non-O blood
      groups have been associated with an increased risk of venous thromboembolism
      (VTE) in adults, with a compounding effect in the presence of thrombophilia or
      cancer. We hypothesized that among children with ALL receiving a standardized
      protocol, there would be an increased risk of thrombotic events in non-O compared
      with O blood group patients. In a retrospective study of 523 children with ALL
      from June 1995 to April 2013, there were 56 (10.7%) thromboembolic events.
      Patients with VTE were compared with the whole cohort, based on blood group, age,
      sex, leukemia phenotype, and clinical risk category. Among children with VTE, 42
      (75%) had non-O and 14 (25%) had O blood group, compared with 302 (57.7%) non-O
      and 221 (42.3%) O blood groups in the cohort. Non-O blood group was confirmed as
      an independent risk factor for VTE in multivariate analysis. This is the first
      study to report a significant association between non-O blood groups and VTE in
      children with cancer. 

PMID- 25851554
TI  - Large Cell Neuroendocrine Carcinoma of the Nasopharynx: A Pediatric Case.
AB  - Neuroendocrine tumors are rare, preferentially located in the gastrointestinal
      tract or in the lungs. We present the case of a 9-year-old child, presenting with
      a tissue mass involving the nasopharynx and associated with multiple pulmonary
      and bone metastases. The immunohistochemical analysis showed a proliferation of
      large tumor cells stained with Chromogranin A and Synaptophysin. The diagnosis of
      multimetastatic large cell neuroendocrine carcinoma was made. This tumor is
      infrequent in this location and particularly in children. This case describes the
      pathologic aspects and immunohistochemical results and presents a discussion of
      the differential diagnoses. 

PMID- 25851555
TI  - Pediatric Pharyngeal IgD-positive Monoclonal Plasmacytoid and Plasma Cell
      Neoplasm.
AB  - Pediatric neoplasm with monoclonal proliferation of lymphoplasmacytoid
      lymphocytes and plasma cells is exceedingly rare and has essentially never been
      reported in immunocompetent children. Here, we report a previously healthy 13
      year-old girl with a pharyngeal mass and enlarged cervical lymph nodes. The
      pharyngeal mass was composed of CD138, CD79a, MUM-1, IgD, CD20, PAX-5, CD43,
      lambda-restricted monoclonal plasmacytoid, and plasma cells. Scattered CD20, PAX
      5 B cells were present in the background. The patient was treated as localized
      non-Hodgkin lymphoma (stage II) with cyclophosphamide, doxorubicin, vincristine,
      and prednisone and is in complete remission at 17 months from the last
      chemotherapy. 

PMID- 25851556
TI  - A Sporadic Case of Advanced Metastatic Cholangiocarcinoma in a Child: A Case
      Report and Review of Literature.
AB  - Cholangiocarcinoma (CC) is a malignancy of the biliary tract that commonly
      presents in the seventh decade of life, but is extremely rare in children. We
      report on a sporadic case of malignant CC in an 11-year-old female. Originally
      presenting with dyspnea, chest x-ray identified multiple pulmonary metastases,
      and various imaging modalities revealed diffuse disease spread throughout the
      liver and lungs. Following pathologic diagnosis of CC, aggressive treatment was
      initiated with a dramatic initial response to chemotherapy, however, as often
      occurs with advanced disease in adults, this patient ultimately succumbed to the
      disease. 

PMID- 25851557
TI  - Fatal Acute Myeloid Leukemia With 11q23 MLL Gene Rearrangement Following
      Mitoxantrone Treatment in a Case of Childhood-onset Multiple Sclerosis.

PMID- 25851558
TI  - Adolescent reactions to icon-driven response modes in a tablet-based health
      screening tool.
AB  - Increasingly popular touch-screen electronic tablets offer clinics a new medium
      for collecting adolescent health screening data in the waiting area before
      visits, but there has been limited evaluation of interactive response modes. This
      study investigated the clarity, comprehensibility, and utility of icon-driven and
      gestural response functions employed in one such screening tool, TickiT. We
      conducted cognitive processing interviews with 30 adolescents from Vancouver
      (aged 14-20 years, 60% female, 30% English as a second language) as they
      completed the TickiT survey. Participants used seven different interactive
      functions to respond to questions across 30 slides, while being prompted to
      articulate their thoughts and reactions. The audio-recorded, transcribed
      interviews were analyzed for evidence of comprehension, nuances in response
      choices, and youth interest in the modes. Participants were quite receptive to
      the icon response modes. Across demographics and cultural backgrounds, they
      indicated question prompts were clear, response choices appropriate, and response
      modes intuitive. Most said they found the format engaging and would be more
      inclined to fill out such a screening tool than a paper-and-pencil form in a
      clinical setting. Given the positive responses and ready understanding of these
      modes among youth, clinicians may want to consider interactive icon-driven
      approaches for screening. 

PMID- 25851559
TI  - Clinical Decision Support and Perioperative Peripheral Nerve Injury: A Quality
      Improvement Project.
AB  - Decision support at the point of care has been demonstrated to be an effective
      tool in providing a safe environment and improving patient outcomes. The
      operating room is typically an area where advanced technology is introduced to
      nurses on a regular basis. This quality improvement project focused on preventing
      a peripheral nerve injury, which is an example of a postoperative adverse event
      that is considered preventable. Injury of a peripheral nerve is the result of
      compression, hyperextension, flexion, or ischemia surrounding the nerve. The
      goals for this project were to improve the knowledge of peripheral nerve injury
      of the operating room nurses, design and implement a peripheral nerve injury
      assessment screen that could provide decision support within the operating room
      record, improve the nursing documentation of peripheral nerve injury
      interventions, and (long term) decrease the incidence of peripheral nerve injury.
      A decision support screen within the operating room record was designed to
      supplement the operating room nurse's risk assessment for peripheral nerve
      injury. The components of this project involved a preliminary and postproject
      surveys on peripheral nerve injury knowledge, an educational presentation, and a
      retrospective random review of nursing documentation in the operating room
      electronic health records. Project results demonstrated a significant increase in
      nursing documentation of peripheral nerve injury interventions (63%-92%) and a
      positive attitude toward their exposure to basic decision support (P = .046).
      Recommendations for future studies and establishing a standardized coding system
      for peripheral nerve injury identification were identified. 

PMID- 25851560
TI  - Laying the Groundwork for NCLEX Success: An Exploration of Adaptive Quizzing as
      an Examination Preparation Method.
AB  - First-time NCLEX-RN pass rates are an important indicator of nursing school
      success and quality. Nursing schools use different methods to anticipate NCLEX
      outcomes and help prevent student failure and possible threat to accreditation.
      This study evaluated the impact of a shift in NCLEX preparation policy at a BSN
      program in the southeast United States. The policy shifted from the use of
      predictor score thresholds to determine graduation eligibility to a more
      proactive remediation strategy involving adaptive quizzing. A descriptive
      correlational design evaluated the impact of an adaptive quizzing system designed
      to give students ongoing active practice and feedback and explored the
      relationship between predictor examinations and NCLEX success. Data from student
      usage of the system as well as scores on predictor tests were collected for three
      student cohorts. Results revealed a positive correlation between adaptive
      quizzing system usage and content mastery. Two of the 69 students in the sample
      did not pass the NCLEX. With so few students failing the NCLEX, predictability of
      any course variables could not be determined. The power of predictor examinations
      to predict NCLEX failure could also not be supported. The most consistent factor
      among students, however, was their content mastery level within the adaptive
      quizzing system. Implications of these findings are discussed. 

PMID- 25851561
TI  - Extracorporeal Treatment in Severe Hypertriglyceridemia-Induced Pancreatitis.
AB  - Plasmapheresis is a well-accepted treatment option in severe hypertriglyceridemia
      induced pancreatitis (HTGP). The rationale behind this approach is the depletion
      of triglycerides and the reduction of inflammatory cytokines. The time span
      between onset of clinical symptoms and start of plasmapheresis might have an
      important impact on mortality. Hyperviscosity of patients' plasma represents
      another special challenge for the applied separation technology. The procedures
      can be performed either by centrifugal device (CFD) or membrane based (MBS)
      units. The present study reports the outcome of 10 patients suffering from HTG.
      The expected mortality of the collective was 25%. Plasmapheresis was started
      after an average 16.3 h (SD +/- 6.7 h) after onset of symptoms. No mortality
      occurred. Apheresis was statistically equally effective with both devices. A
      median of 3 sessions reduced the TG level to normal and correlated with patients'
      improvement. During follow up, three patients developed a pancreatic pseudocyst
      requiring surgical intervention without further complication. 

PMID- 25851562
TI  - Combining malaria control with house electrification: adherence to recommended
      behaviours for proper deployment of solar-powered mosquito trapping systems,
      Rusinga Island, western Kenya.
AB  - OBJECTIVE: To investigate community adherence to recommended behaviours for
      proper deployment of solar-powered mosquito trapping systems (SMoTS) after 3- to
      10-week use. METHODS: Solar-powered mosquito trapping system, which also provided
      power for room lighting and charging mobile phones, were installed in houses in
      Rusinga Island, western Kenya. We used a structured checklist for observations
      and a semi-structured questionnaire for interviews in 24 homesteads. We also
      analysed the subject of 224 community calls to the project team for technical
      maintenance of SMoTS. RESULTS: Most respondents cared for SMoTS by fencing,
      emptying and cleaning the trap. Our observations revealed that most traps were
      fenced, clean and in good working condition. A significantly higher proportion of
      community calls was lighting-related. Lighting was the main reason respondents
      liked SMoTS because it reduced or eliminated expenditure on kerosene. However,
      some respondents observed they no longer heard sounds of mosquitoes inside their
      houses. All respondents reportedly slept under insecticide-treated nets (ITNs)
      before receiving SMoTS. After receiving SMoTS, most respondents reportedly
      continued to use ITNs citing that the project advised them to do so. Some beach
      residents stopped using ITNs because they no longer heard mosquitoes or due to
      heat discomfort caused by lights. CONCLUSION: Electricity-related incentives
      played a greater role in encouraging adherence to recommended behaviours for
      proper deployment of SMoTS than the potential health benefits in the early stages
      of the intervention. Although energy-related financial incentives may play a
      role, they are insufficient to ensure adherence to health advice, even in the
      short term. Ongoing community engagement and research monitors and addresses
      adherence to recommended behaviours including continuation of current malaria
      control strategies.

PMID- 25851563
TI  - Relationship between azathioprine dosage, 6-thioguanine nucleotide levels, and
      therapeutic response in pediatric patients with IBD treated with azathioprine.
AB  - BACKGROUND: Azathioprine (AZA) is commonly used to treat IBD either alone or in
      combination with mesalazine. However, there are relatively few studies concerning
      the relationship between AZA dose, thiopurine metabolite levels, and therapeutic
      response in pediatric patients treated with both AZA and mesalazine. METHODS: We
      retrospectively investigated the relationship between AZA dose, thiopurine
      metabolite levels, and therapeutic response in 137 pediatric patients with IBD
      treated with AZA using multilevel analysis. Additional factors affecting
      metabolite levels and therapeutic response were also analyzed. RESULTS: A
      positive correlation was observed between AZA dosage and 6-thioguanine nucleotide
      (6-TGN) level (P < 0.0001). Variant TPMT genotype (P < 0.001) and concomitant use
      of mesalazine (P < 0.001) were predictors of higher 6-TGN levels. Leukopenia (P =
      0.025) and lymphopenia (P = 0.045) were associated with higher levels of 6-TGN.
      Poor AZA compliance affected median 6-TGN levels (P < 0.001). The frequency of
      patients with median 6-TGN levels >235 pmol per 8 * 10(8) red blood cells was the
      highest in the sustained therapeutic response group (P = 0.015). Age, sex, IBD
      type, and duration of AZA therapy did not influence 6-TGN levels or therapeutic
      effect. CONCLUSIONS: AZA dosage is positively correlated with 6-TGN level. Higher
      6-TGN levels are related to leukopenia, lymphopenia, and concurrent use of
      mesalazine. These results provide the rationale for monitoring metabolites to
      optimize drug dosing and minimize drug-related toxicity. In addition, maintenance
      of 6-TGN levels within a beneficial therapeutic range by direct monitoring should
      be helpful in attaining therapeutic efficacy, although this possibility should be
      verified in prospective studies.

PMID- 25851564
TI  - Predicting Endoscopic Crohn's Disease Activity Before and After Induction Therapy
      in Children: A Comprehensive Assessment of PCDAI, CRP, and Fecal Calprotectin.
AB  - BACKGROUND: Mucosal healing (MH) is a vital early endpoint in management of
      Crohn's disease (CD). MH depends on endoscopic assessment and there is increasing
      interest in non-invasive proxies, Pediatric Crohn's Disease activity Index
      (PDCAI), C-reactive protein (CRP) and fecal calprotectin (FC). These proxies must
      be validated against endoscopic disease activity (SES-CD) at diagnosis and after
      induction therapy in well characterized cohorts of children with CD. METHODS: A
      prospective cohort of 24 newly diagnosed children (<16 yr) with luminal CD
      quantifiable on complete ileo-colonoscopy had paired PCDAI, CRP, FC and SES-CD at
      diagnosis and after 8 weeks therapy with exclusive enteral nutrition or steroids.
      RESULTS: At diagnosis: PCDAI had poor correlation (r = 0.33); CRP (r = 0.54) and
      FC (r = 0.46) had moderate correlation with SES-CD. After induction therapy:
      11/24 had inactive disease (SES-CD 0-2); PCDAI (r = 0.34) and CRP (0.28) had poor
      correlation with SES-CD, many children with SES-CD >=3 having normalization of
      both PCDAI and CRP. FC had good correlation (r = 0.50) but many with SES-CD 0-2
      had FC >200 MUg/gm stool. FC<500 (positive likelihood ratio, 3.2) and FC drop
      >50% (positive likelihood ratio, 3.8) had greater predictive value for inactive
      disease. Composite PCDAI (<10), CRP (<5 mg/dl) & FC <500 MUg had excellent
      Negative LR (0.2) predicting inactive disease. CONCLUSIONS: PCDAI is unreliable
      for endoscopic disease severity assessment. Only FC correlates with endoscopic
      activity after therapy but cut off <200 MUg is too high for defining endoscopic
      recovery in children. Composite normalized PCDAI, CRP and FC <500 MUg should be
      considered the non-invasive endpoint for treatment response in pediatric CD.

PMID- 25851565
TI  - A functional ruthenium(ii) complex for imaging biothiols in living bodies.
AB  - A unique ruthenium(ii) complex, [Ru(bpy)2(DNS-bpy)](PF6)2 [bpy: 2,2'-bipyridine,
      DNS-bpy: 4-(2,4-dinitrophenylthio)-2,2'-bipyridine], that can act as a probe for
      the recognition and luminescence sensing of biothiols has been designed and
      synthesized. Due to the presence of effective photo-induced electron transfer
      (PET) from the potent electron donor (Ru-bpy centre) to the strong electron
      acceptor (2,4-dinitrophenyl moiety), the Ru(ii) complex itself is weakly
      luminescent. Reaction of [Ru(bpy)2(DNS-bpy)](PF6)2 with biothiols leads to the
      replacement of the 2,4-dinitrophenyl moiety by biothiols, which results in the
      loss of PET within the complex, to allow recovery of the MLCT-based emission of
      the Ru(ii) complex with an 80-fold increase in luminescence intensity. Taking
      advantage of the high specificity and sensitivity, and the excellent
      photophysical properties of Ru(ii) complexes, [Ru(bpy)2(DNS-bpy)](PF6)2 was
      successfully applied to the luminescence imaging of biothiols in living Daphnia
      magna. The results demonstrated the practical applicability of [Ru(bpy)2(DNS
      bpy)](PF6)2 as a luminescent probe for the monitoring of biothiols in living
      bodies. 

PMID- 25851566
TI  - SMT or TOFT? How the two main theories of carcinogenesis are made (artificially)
      incompatible.
AB  - The building of a global model of carcinogenesis is one of modern biology's
      greatest challenges. The traditional somatic mutation theory (SMT) is now
      supplemented by a new approach, called the Tissue Organization Field Theory
      (TOFT). According to TOFT, the original source of cancer is loss of tissue
      organization rather than genetic mutations. In this paper, we study the
      argumentative strategy used by the advocates of TOFT to impose their view. In
      particular, we criticize their claim of incompatibility used to justify the
      necessity to definitively reject SMT. First, we note that since it is difficult
      to build a non-ambiguous experimental demonstration of the superiority of TOFT,
      its partisans add epistemological and metaphysical arguments to the debate. This
      argumentative strategy allows them to defend the necessity of a paradigm shift,
      with TOFT superseding SMT. To do so, they introduce a notion of incompatibility,
      which they actually use as the Kuhnian notion of incommensurability. To justify
      this so-called incompatibility between the two theories of cancer, they move the
      debate to a metaphysical ground by assimilating the controversy to a fundamental
      opposition between reductionism and organicism. We show here that this
      argumentative strategy is specious, because it does not demonstrate clearly that
      TOFT is an organicist theory. Since it shares with SMT its vocabulary, its
      ontology and its methodology, it appears that a claim of incompatibility based on
      this metaphysical plan is not fully justified in the present state of the debate.
      We conclude that it is more cogent to argue that the two theories are compatible,
      both biologically and metaphysically. We propose to consider that TOFT and SMT
      describe two distinct and compatible causal pathways to carcinogenesis. This view
      is coherent with the existence of integrative approaches, and suggests that they
      have a higher epistemic value than the two theories taken separately. 

PMID- 25851567
TI  - Major changes to care system need to be properly funded to succeed, warn
      charities.

PMID- 25851568
TI  - Transparent and luminescent ionogels composed of Eu(3+)-coordinated ionic liquids
      and poly(methyl methacrylate).
AB  - We report here on transparent and luminescent ionogels that consist of ionic
      ternary europium (III) complexes and the inexpensive non-toxic compound,
      poly(methyl methacrylate) (PMMA) and that were formed by dissolving these
      complexes in methacrylate (MMA) monomers followed by in situ polymerization. The
      resulting ionogels show a bright red emission under near-UV light irradiation.
      Luminescence data confirm the energy transfer from terpyridine-functionalized
      ionic liquid to Eu(3+) ions.

PMID- 25851570
TI  - The mystique of veins revisited.

PMID- 25851572
TI  - Editor's note.

PMID- 25851571
TI  - Phlebosclerosis, phlebothrombosis, and thrombophlebitis: A current perspective.
AB  - Phlebosclerosis, phlebothrombosis, and thrombophlebitis are three fundamentally
      different structural changes affecting superficial, deep, visceral, and cerebral
      veins. Phlebosclerosis is a frequent, age-dependent fibrotic degeneration of one
      or all three wall layers. It does not represent a distinct disease entity but may
      impair the venous function and contribute to the development of thrombosis.
      Phlebothrombosis represents a serious circulatory disorder. It may be due to a
      variety of factors including phlebitis, i.e., a primary inflammatory disease of
      the venous wall. Thrombophlebitis may be a relatively harmless disorder, such as
      represented by idiopathic skipping phlebitis (phlebitis saltans), or it may be a
      symptom of an underlying systemic disease. Whereas phlebothrombosis in
      nonvaricose veins is suspicious of an underlying malignancy or a coagulation
      disorder, thrombophlebitis is not related to malignancies but may accompany
      Buerger's disease or other systemic vasculitides. The histopathological
      distinction of phlebothrombosis and thrombophlebitis is therefore of paramount
      importance and determines further clinical investigations. A proposal for
      classification of thrombophlebitides and some guidelines for clinicopathological
      differentiation of the various types of phlebitides are presented. 

PMID- 25851569
TI  - The Use of Induced Pluripotent Stem Cell Technology to Advance Autism Research
      and Treatment.
AB  - Autism spectrum disorders (ASDs) are a heterogeneous group of neurodevelopmental
      disorders sharing a core set of symptoms, including impaired social interaction,
      language deficits, and repetitive behaviors. While ASDs are highly heritable and
      demonstrate a clear genetic component, the cellular and molecular mechanisms
      driving ASD etiology remain undefined. The unavailability of live patient
      specific neurons has contributed to the difficulty in studying ASD
      pathophysiology. The recent advent of induced pluripotent stem cells (iPSCs) has
      provided the ability to generate patient-specific human neurons from somatic
      cells. The iPSC field has quickly grown, as researchers have demonstrated the
      utility of this technology to model several diseases, especially neurologic
      disorders. Here, we review the current literature around using iPSCs to model
      ASDs, and discuss the notable findings, and the promise and limitations of this
      technology. The recent report of a nonsyndromic ASD iPSC model and several
      previous ASD models demonstrating similar results points to the ability of iPSC
      to reveal potential novel biomarkers and therapeutics. 

PMID- 25851573
TI  - Introduction International meeting on chagasic heart disease: South American
      Italian Cooperation on a vital cardiologic issue.

PMID- 25851574
TI  - Pathogenesis of chronic Chagas' myocarditis: An overview.
AB  - The evidence provided by both human and animal studies on chronic Chagas' heart
      disease suggests that the development of the chronic fibrosing myocarditis is
      related to progressive and additive focal cellular necrosis with associated
      inflammatory lymphomononuclear infiltrate, reactive and reparative myocardial
      fibrosis, surrounding myocyte hypertrophy. These processes may be initiated and
      perpetuated by alterations in the myocardial microcirculation and by autoimmune
      factors. These findings could foster future therapeutic strategies in the
      management of chronic chagasic patients to optimize the medical treatment and
      hopefully to improve prognosis. 

PMID- 25851575
TI  - Chagas' disease: Microvascular and interstitial matrix abnormalities
      characteristic of congestive cardiomyopathy of diverse etiology.
AB  - Chagas' disease, due to a chronic and persistent infection with the parasite
      Trypanosoma cruzi, is the cause of one of the most prevalent forms of congestive
      cardiomyopathy in South and Central America. In common with other congestive
      cardiomyopathies due to acquired and hereditary etiologies seen worldwide,
      chagasic cardiomyopathy is characterized by cardiomegaly, ventricular chamber
      remodeling, myocellular necrosis, and multifocal areas of interstitial and
      replacement fibrosis. The microscopic presence of the parasite in the late stages
      of the disease is rare. This review examines some of the evidence for the role of
      a dysfunctional microvasculature as a pathophysiological mechanism for myocardial
      damage in chagasic cardiomyopathy. Perturbations of the interstitial connective
      tissue matrix in Chagas' disease also are described in regard to the remodeling
      characteristic of the affected ventricle. Similar abnormalities of the
      microvasculature and matrix have been reported in other congestive
      cardiomyopathies, thereby suggesting that common pathophysiologic mechanisms may
      lead to ventricular damage even when the initiating etiologic agent is different.
      Preventive treatment or palliation of Chagas' cardiomyopathy and other congestive
      cardiomyopathies may result from a better understanding of these secondary
      pathogenetic events. 

PMID- 25851576
TI  - Myocardial inflammatory infiltrate in human chronic chagasic cardiomyopathy:
      Immunohistochemical findings.
AB  - Chagas' disease is the most common form of chronic myocarditis in the world. It
      is characterized by a progressive chronic myocarditis that leads to cardiomegaly,
      arrhythmias, cardiac failure, and thromboembolic phenomena. This communication
      reports studies on the immunohistochemistry of chronic infiltrates in 30
      endomyocardial biopsies and in contracting and specialized myocardium of
      autopsies of four patients suffering from Chagas' cardiomyopathy. Expression of
      the following antigens was studied: common leucocyte antigen (CLA-CD45R), L
      26(CD20), CD68, kappa and lambda light chains and T-UCLH-1 (CD45RO), and MB-1.
      Streptavidin-peroxidase and streptavidin-alkaline phosphatase with biotinylated
      anti-mouse IgG were used as detection systems. Double immunostaining for the
      simultaneous demonstration of T lymphocytes (CD45R0) and macrophages was
      performed using both immunoenzymatic techniques consecutively. Expression of CD31
      was detected for the demonstration of endothelial cells. In endomyocardial
      biopsies, tissue forms of trypanosomes were not found. The percentage of fibrous
      tissue was 24.1% +/- 12.8% (range 8.2%-49%). Eosinophils were scarce (1/high
      power field), but associated with necrotic areas of the myocardium. Mast cells
      were scarce or absent. They were always situated in fibrotic areas. The most
      remarkable finding was the presence of infiltrates consisting of macrophages and
      CLA-positive mononuclear cells. Twenty-six and one-half percent of them were T
      lymphocytes, and 10.5% were B lymphocytes. Lymphocytic infiltration was
      particularly associated with necrotic and degenerative myocardial lesions. Thirty
      percent of the infiltrate was composed of macrophages (positive CD68 cells). The
      remaining infiltrate was composed of mononuclear cells resembling macrophages and
      CLA-negative mononuclear cells. Contacts between CD68-positive cells and T
      lymphocytes were frequently found. CD31 antibodies clearly pointed out normal
      endothelial cells, in either normal or damaged vessels. No isolated cells
      positive for these antibodies were found within the mononuclear infiltrate. In
      autopsied hearts, myocardial lesions consisted of a chronic inflammatory process
      with fibrotic scars and extensive mononuclear infiltrates. No amastigote nests
      were found. A statistically significant difference (p < 0.05) was obtained when
      the percentage of fibrosis was compared in the specialized and contracting
      myocardiums (51.6% +/- 18% vs. 43.4 % +/- 8%). Eosinophils were scarce in
      infiltrates, reaching 5%, and they were associated with necrotic myocardium. Mast
      cells also were scarce or absent in specialized and in contracting myocardium.
      Almost all the lymphocytic population was T lymphocytes. Such infiltrates were
      more prominent in the working myocardium (39%) and in the specialized cells of
      the left branch of the His bundle than in the atrioventricular node and in the
      right Hisian branch (34.4%). The 31% of mononuclear cells were CD68 positive,
      thus corresponding to macrophages. Contacts among T lymphocytes and macrophages
      were frequently observed. Although much that is concerned with Chagas'
      cardiomyopathy is controversial, these may be the major ingredients for its
      pathogenesis: the parasite or a part of it, lymphocytes and macrophages, and
      fibrosis. Then a multifactorial or "combined theory" may be suggested to explain
      the sequence of events that lead to the chronic stage of the disease. 

PMID- 25851577
TI  - Pathologic substrates for arrhythmogenesis in chronic chagasic cardiopathy.
AB  - Here are described the results of a histopathological study on 12 autopsy hearts
      of subjects deceased secondary to chronic chagasic cardiopathy in order to
      clarify the nature and the pathogenetic mechanism of its arrhythmogenic
      potential. The arrhythmogenic hazards of chagasic cardiomyopathy are mainly due
      to the striking disruptive fibrotic changes with ensuing electrical instability
      of the ventricular myocardium. Lesions of the conduction system, focal
      epiperineuritis, and an inconstant and questionable "neuronal depletion" of the
      cardiac plexuses in the disease play a concomitant role. 

PMID- 25851578
TI  - Cardiac extrinsic neuropathy: Lesions of the mediastinal paraganglia in chronic
      chagasic cardiomyopathy.
AB  - The pathology of cardiac innervation, both intrinsic and external to the heart
      (mediastinal paraganglia included), is scarcely known, yet it can be critical to
      life-threatening disorders in cardiac performance or to reflexes discharging
      outside the heart, or both. This article focuses on such a fundamental and ill
      understood subject through an anatomoclinical outlook of mediastinal paraganglia
      lesions in the setting of sudden death in chronic chagasic cardiomyopathy. 

PMID- 25851579
TI  - Neuropathology of chronic chagasic cardiopathy: A diagnostic reassessment.
AB  - Intrinsic innervation changes in chronic chagasic cardiopathy long have been
      regarded as pathognomonic to the disease clinicopathologically and acritically
      ascribed to incurable "neuronal depletion." This allegedly diffuse, frequent, and
      devastating damage to parasympathetic cardiac ganglia was absent in the seven
      cases we examined and was not demonstrated by reliable neuropathologic diagnosis
      in former studies from the literature, where the evidence of Terplan nodules, the
      very hallmark of autonomic neuronal loss, had been lamentably disregarded. Thus,
      dysautonomic manifestations in chronic chagasic cardiopathy should be attributed
      to the frequent and widespread finding of neuritic involvement in the severe
      (auto-) immune fibrosing myocarditis peculiar to the disease. 

PMID- 25851580
TI  - Uptake of aromatic compounds by DNA: Toward the environmental application of DNA
      for cleaning water.
AB  - HYPOTHESIS: Although the interaction of DNA with various types of intercalating
      chemicals, such as planar polycyclic aromatic compounds, has been extensively
      investigated over the past several decades, little is known about the
      relationship between the structure of a DNA binder and its affinity for DNA. The
      use of DNA as an adsorbent for environmental cleaning purposes requires
      information on its affinity for organic chemicals with different structures.
      EXPERIMENT: In the present study we investigated the binding of DNA to aromatic
      chemicals with various structures and charges by three methods: binding of
      organic chemicals to DNA followed by removal by precipitation with cationic
      nanoparticles (1) or a cationic surfactant (2), and absorption of organic
      chemicals by a DNA hydrogel (3). FINDINGS: The results showed that, for most
      neutral organic chemicals, the hydrophobicity of the organic molecule is the main
      driving force for efficient binding to DNA. The double-helicity of DNA
      contributed to stronger binding to most of the compounds. The efficiency of the
      uptake of organic chemicals increased substantially when a hydrophobic cationic
      surfactant was used for DNA-complex condensation and removal. The potential
      environmental application of DNA as an adsorbent for the removal of aromatic
      organic pollutants from water is discussed.

PMID- 25851581
TI  - The fate of silica based Stober particles soaked into growth media (RPMI and
      M254): A DLS and zeta-potential study.
AB  - Understanding the mechanisms involved in the interaction of biological systems
      with inorganic materials is of great importance and interest in both fundamental
      and applied disciplines in several different fields such as astrobiology,
      ecology, biology, biotechnology, engineering, and medicine. In this context, this
      paper investigates the interaction of biomacromolecules with submicrometric
      silica gel particles (NP) obtained through the Stober method. Surprisingly,
      particles size reduction is observed after their dispersion into two different
      reconstituted growth media (RPMI and M254). This effect was related to the nature
      of the Stober particles and the mechanism of their formation. The experimental
      results can be explained arguing that a biomacromolecule corona rapidly forms on
      NP incubated in both RPMI and M254 growth media. The results suggest that
      hydrolytic attack at incompletely condensed internal surface valence sites as
      well as interactions between NPs surface and the components of the growth media
      reverse the aggregation process, giving smaller disaggregated particles
      surrounded by a biomacromolecule corona. Moreover it was assessed that, at longer
      incubation time, the particles slightly grow probably due to interlocking of
      biomacromolecules in the corona. Furthermore, experimental results confirm that
      formation of this corona is a competitive and dynamic process. The present paper
      shows that the described effects (as size changes) are strongly dependent on the
      nature of the growth medium. 

PMID- 25851582
TI  - RGD-modified pH-sensitive liposomes for docetaxel tumor targeting.
AB  - Phosphatidylethanolamine-based pH-sensitive liposomes of various compositions
      have been described as efficient systems for delivery of therapeutic molecules
      into tumor cells. The aim of this work was to develop a drug delivery system
      based on pH-sensitive liposomes (PLPs) that were modified with arginine-glycine
      aspartic acid (RGD) peptide to enhance the effectiveness of docetaxel treatment.
      Docetaxel/coumarin-6 loaded PLPs were prepared by the thin-film dispersion method
      and characterized in detail, including by particle size, polydispersity, zeta
      potential and drug encapsulation efficiency. In vitro studies using MCF-7,
      HepG2and A549 cells were employed to investigate cytotoxicity and cellular uptake
      of the drug solution or docetaxel/coumarin-6 loaded PLPs. The accumulation of 7
      nitro-2-1,3-benzoxadiazol-4-yl (NBD)-labeled liposomes in vivo was studied
      through tumor section imaging of xenograft mouse models of MCF-7 24h after
      intravenous administration. The particle size of the non-coated or RGD modified
      PLPs ranged between 146 and 129nm. Drug release in vitro was modestly prolonged
      and had good pH sensitivity. In the in vitro study, RGD-coated PLPs showed higher
      cytotoxicity and cellular uptake relative to non-coated ones. The results of the
      in vivo study showed that RGD-coated PLPs had higher fluorescence, which
      suggested a more efficient accumulation than normal PLPs in tumors. In
      conclusion, these results confirmed RGD-modified PLPs as a potential drug
      delivery system to achieve controlled release and tumor targeting. 

PMID- 25851583
TI  - High-Intensity Interval Exercise and Postprandial Triacylglycerol.
AB  - This review examined if high-intensity interval exercise (HIIE) reduces
      postprandial triacylglycerol (TAG) levels. Fifteen studies were identified, in
      which the effect of interval exercise conducted at an intensity of >65% of
      maximal oxygen uptake was evaluated on postprandial TAG levels. Analysis was
      divided between studies that included supramaximal exercise and those that
      included submaximal interval exercise. Ten studies examined the effect of a
      single session of low-volume HIIE including supramaximal sprints on postprandial
      TAG. Seven of these studies noted reductions in the postprandial total TAG area
      under the curve the morning after exercise of between ~10 and 21% compared with
      rest, but three investigations found no significant difference in TAG levels.
      Variations in the HIIE protocol used, inter-individual variation or insufficient
      time post-exercise for an increase in lipoprotein lipase activity are proposed
      reasons for the divergent results among studies. Five studies examined the effect
      of high-volume submaximal interval exercise on postprandial TAG. Four of these
      studies were characterised by high exercise energy expenditure and effectively
      attenuated total postprandial TAG levels by ~15-30%, but one study with a lower
      energy expenditure found no effect on TAG. The evidence suggests that
      supramaximal HIIE can induce large reductions in postprandial TAG levels but
      findings are inconsistent. Submaximal interval exercise offers no TAG metabolic
      or time advantage over continuous aerobic exercise but could be appealing in
      nature to some individuals. Future research should examine if submaximal interval
      exercise can reduce TAG levels in line with more realistic and achievable
      exercise durations of 30 min per day.

PMID- 25851585
TI  - Antepartum use of Epi-No birth trainer for preventing perineal trauma: systematic
      review.
AB  - INTRODUCTION AND HYPOTHESIS: In this systematic review we aimed to assess if the
      Epi-No birth trainer used during antepartum could prevent perineal trauma in
      nulliparous women. METHODS: We searched CENTRAL, MEDLINE, EMBASE, Scielo, and
      Conference abstracts, looking for randomized controlled studies (RCT). High
      heterogeneity (i(2) > 50 %) was corrected with random models. All studies were
      analyzed according to their quality and risk of bias. Nulliparous women or women
      whose previous pregnancy ended before 21 weeks' gestation were included and the
      main outcome measures were: episiotomy rates, perineal tears, severe (3rd/4th)
      perineal tears, and intact perineum. RESULTS: Five studies were included (1,369
      participants) for systematic review and two of them (932 participants) were
      eligible for meta-analysis. Epi-No did not reduce episiotomy rates (RR 0.92
      [95%CI 0.75-1.13], n = 710, p =0.44; two studies; fixed model) and second stage
      of labor (MD -12.50 [95%CI -29.62, -4.62], n = 162, p = 0.54; one study; fixed
      model), and did not increase intact perineum (RR 1.15 [95 % CI 0.81-1.64], n =
      705, p = 0.43; two studies; random model). No influence of Epi-No on reducing all
      perineal tears (RR 0.99 [95%CI 0.84-1.17], n = 705, p = 0.93, two studies; fixed
      model) or severe (3rd/4th) perineal tears (RR 1.31 [95%CI 0.72-2.37], n = 705, p
      = 0.38, two studies; fixed model). Mean birthweight of the Epi-No group was
      higher than that of the control group in both studies, with no statistical
      significance. CONCLUSION: Epi-No birth trainer is a device that did not reduce
      episiotomy rates and had no influence on reducing perineal tears.

PMID- 25851586
TI  - Midterm results of robot-assisted sacrocolpopexy.
AB  - INTRODUCTION AND HYPOTHESIS: Robotic assistance simplifies laparoscopic
      procedures. We hypothesize that robot-assisted sacrocolpopexy is a rapid and safe
      procedure with satisfying short-term and midterm functional results. METHODS:
      After informed consent, we enrolled 101 consecutive patients undergoing
      sacrocolpopexy at Alfried Krupp Hospital, Essen, Germany. After a median follow
      up of 22 months, we assessed midterm functional results as the primary endpoint.
      Secondary endpoints included surgical duration, blood loss, intraoperative
      complications, and postoperative complications. We described frequencies as
      counts (percent) and continuous data as median [interquartile range (Q1-Q3)] or
      mean [standard deviation (SD)], as appropriate. RESULTS: We enrolled 101
      patients. The mean age was 69 years (SD 11); 75 women (74.3 %) had undergone
      previous abdominal surgery. Among the patients, 95 (94.1 %) presented with
      anterior vaginal wall prolapse Baden-Walker grade 2-3, 74 (73.3 %) vaginal vault
      prolapse, and 9 (8.9 %) concomitant rectocele. Fifty (50 %) patients underwent a
      modified Burch procedure in addition to sacrocolpopexy. The median surgical
      duration was 96 min (Q1-Q3 83-130). There were six (5.9 %) minor intraoperative
      complications but no conversions to open surgery. Postoperatively, we registered
      five (4.9 %) Clavien-Dindo grade I complications, three (3.0 %) grade II
      complications, and one (1.0 %) grade III complication. After a median follow-up
      of 22 months (Q1-Q3 12-49), the patients reported significant decreased impact of
      pelvic organ prolapse (POP) on quality of life as well as bother resulting from
      POP symptoms. The overall success rate, defined as none or minor impact of POP on
      quality of life, was 75 %. CONCLUSIONS: In this single-surgeon study, robot
      assisted sacrocolpopexy was a safe and rapidly performed procedure that achieved
      good medium-term functional results.

PMID- 25851584
TI  - What are the Differences in Injury Proportions Between Different Populations of
      Runners? A Systematic Review and Meta-Analysis.
AB  - BACKGROUND: Many runners suffer from injuries. No information on high-risk
      populations is available so far though. OBJECTIVES: The aims of this study were
      to systematically review injury proportions in different populations of runners
      and to compare injury locations between these populations. DATA SOURCES: An
      electronic search with no date restrictions was conducted up to February 2014 in
      the PubMed, Embase, SPORTDiscus and Web of Science databases. The search was
      limited to original articles written in English. The reference lists of the
      included articles were checked for potentially relevant studies. STUDY
      ELIGIBILITY CRITERIA: Studies were eligible when the proportion of running
      injuries was reported and the participants belonged to one or more homogeneous
      populations of runners that were clearly described. Study selection was conducted
      by two independent reviewers, and disagreements were resolved in a consensus
      meeting. STUDY APPRAISAL AND SYNTHESIS METHODS: Details of the study design,
      population of runners, sample size, injury definition, method of injury
      assessment, number of injuries and injury locations were extracted from the
      articles. The risk of bias was assessed with a scale consisting of eight items,
      which was specifically developed for studies focusing on musculoskeletal
      complaints. RESULTS: A total of 86 articles were included in this review. Where
      possible, injury proportions were pooled for each identified population of
      runners, using a random-effects model. Injury proportions were affected by injury
      definitions and durations of follow-up. Large differences between populations
      existed. The number of medical-attention injuries during an event was small for
      most populations of runners, except for ultra-marathon runners, in which the
      pooled estimate was 65.6%. Time-loss injury proportions between different
      populations of runners ranged from 3.2% in cross-country runners to 84.9% in
      novice runners. Overall, the proportions were highest among short-distance track
      runners and ultra-marathon runners. LIMITATIONS: The results were pooled by
      stratification of studies according to the population, injury definition and
      follow-up/recall period; however, heterogeneity was high. CONCLUSIONS: Large
      differences in injury proportions between different populations of runners
      existed. Injury proportions were affected by the duration of follow-up. A U
      shaped pattern between the running distance and the time-loss injury proportion
      seemed to exist. Future prospective studies of injury surveillance are highly
      recommended to take running exposure and censoring into account.

PMID- 25851588
TI  - Cardiac resynchronisation therapy in 2015: keeping up with the pace.
AB  - Despite improved understanding of the pathophysiology of heart failure (HF) and
      availability of better medical therapies, HF continues to grow as a cause of
      morbidity and mortality in Australia and worldwide. Over the past decade, cardiac
      resynchronisation therapy (CRT), or biventricular pacing, has been embraced as a
      powerful weapon against this growing epidemic. However, much has changed in our
      understanding of dyssynchrony in HF, and this has led to a change in guidelines
      to ensure more appropriate selection of CRT candidates to improve the 'non
      response' rate. More data have also emerged about the use of CRT in atrial
      fibrillation and in pacemaker-dependent patients. There has also been a growing
      focus on multimodality imaging to guide patient selection and lead positioning.
      Exciting new lead technologies are also emerging, with the potential to improve
      CRT outcomes further. 

PMID- 25851589
TI  - Impacts of the Minamata convention on mercury emissions and global deposition
      from coal-fired power generation in Asia.
AB  - We explore implications of the United Nations Minamata Convention on Mercury for
      emissions from Asian coal-fired power generation, and resulting changes to
      deposition worldwide by 2050. We use engineering analysis, document analysis, and
      interviews to construct plausible technology scenarios consistent with the
      Convention. We translate these scenarios into emissions projections for 2050, and
      use the GEOS-Chem model to calculate global mercury deposition. Where technology
      requirements in the Convention are flexibly defined, under a global energy and
      development scenario that relies heavily on coal, we project ~90 and 150 Mg.y(-1)
      of avoided power sector emissions for China and India, respectively, in 2050,
      compared to a scenario in which only current technologies are used. Benefits of
      this avoided emissions growth are primarily captured regionally, with projected
      changes in annual average gross deposition over China and India ~2 and 13 MUg.m(
      2) lower, respectively, than the current technology case. Stricter, but
      technologically feasible, mercury control requirements in both countries could
      lead to a combined additional 170 Mg.y(-1) avoided emissions. Assuming only
      current technologies but a global transition away from coal avoids 6% and 36%
      more emissions than this strict technology scenario under heavy coal use for
      China and India, respectively. 

PMID- 25851587
TI  - A cohesin-OCT4 complex mediates Sox enhancers to prime an early embryonic
      lineage.
AB  - Short- and long-scales intra- and inter-chromosomal interactions are linked to
      gene transcription, but the molecular events underlying these structures and how
      they affect cell fate decision during embryonic development are poorly
      understood. One of the first embryonic cell fate decisions (that is, mesendoderm
      determination) is driven by the POU factor OCT4, acting in concert with the high
      mobility group genes Sox-2 and Sox-17. Here we report a chromatin-remodelling
      mechanism and enhancer function that mediate cell fate switching. OCT4 alters the
      higher-order chromatin structure at both Sox-2 and Sox-17 loci. OCT4 titrates out
      cohesin and switches the Sox-17 enhancer from a locked (within an inter
      chromosomal Sox-2 enhancer/CCCTC-binding factor CTCF/cohesin loop) to an active
      (within an intra-chromosomal Sox-17 promoter/enhancer/cohesin loop) state. SALL4
      concomitantly mobilizes the polycomb complexes at the Soxs loci. Thus, OCT4/SALL4
      driven cohesin- and polycombs-mediated changes in higher-order chromatin
      structure mediate instruction of early cell fate in embryonic cells. 

PMID- 25851590
TI  - Massilia eurypsychrophila sp. nov. a facultatively psychrophilic bacteria
      isolated from ice core.
AB  - Strain B528-3(T), a Gram-stain-negative, rod-shaped, aerobic, facultatively
      psychrophilic bacterium with polar flagella, was isolated from an ice core
      drilled from Muztagh Glacier, Xinjiang, China. The novel isolate was classified
      into the genus Massilia. The 16S rRNA gene sequence of the novel isolate shares a
      pairwise similarity of less than 97% with those of all the type strains of the
      genus Massilia. The major fatty acids of strain B528-3(T) were summed feature 3
      (C16:1omega7c and/or iso-C15:0 2-OH) (57.31%), C16:0 (11.46%) and C18:1omega7c
      (14.72%). The predominant isoprenoid quinone was Q-8. The DNA G + C content was
      62.2 mol% (Tm). The major polar lipids of this bacterium were
      phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol. From
      the genotypic and phenotypic data, it is evident that strain B528-3(T) represents
      a novel species of the genus Massilia, for which the name Massilia
      eurypsychrophila sp. nov. is proposed. The type strain is B528-3(T) ( = JCM
      30074(T) = CGMCC 1.12828(T)).

PMID- 25851591
TI  - Cecembia rubra sp. nov., a thermophilic bacterium isolated from a hot spring
      sediment.
AB  - A Gram-staining negative, rod-shaped bacterium, designated strain YIM 78110(T),
      was isolated from a sediment sample collected from Hehua hot spring in Tengchong,
      Yunnan province, south-west China. The taxonomic status of strain YIM 78110(T)
      was confirmed by a polyphasic approach. 16S rRNA gene sequence analysis indicated
      that strain YIM 78110(T) belongs to the genus Cecembia, displaying 96.8% and
      94.7% sequence similarity with the two most closely related type strains,
      Cecembia calidifontis RQ-33(T) and Cecembia lonarensis LW9T, respectively. The
      low value of DNA-DNA hybridization (52.3 +/- 2.3%) between strain YIM 78110(T)
      and its closest neighbour, Cecembia calidifontis RQ-33(T), indicated that this
      new isolate represented a different genomic species in the genus Cecembia. The
      temperature for growth ranged from 30 to 50  degrees C. The pH for growth ranged
      from pH 4.0 to 10.0, with NaCl tolerance of 0.5-6.0% (w/v). The predominant
      menaquinone of strain YIM 78110(T) was MK-7 and the major polar lipid was
      phosphatidylethanolamine. The major fatty acids were iso-C15:0 and C15:0. The DNA
      G+C content was 47.1 mol%. On the basis of physiological, biochemical and
      phylogenetic analyses, it is proposed that strain YIM 78110(T) represents a novel
      species of the genus Cecembia, for which the name Cecembia rubra sp. nov. is
      proposed. The type strain is YIM 78110(T) ( = CCTCC AB2013287(T) = DSM 28057(T)).

PMID- 25851592
TI  - Escherichia marmotae sp. nov., isolated from faeces of Marmota himalayana.
AB  - The taxonomic position of a group of seven closely related lactose-negative
      enterobacterial strains, which were isolated from fresh faecal samples of Marmota
      himalayana collected from the Qinghai-Tibetan plateau, China, was determined by
      using a polyphasic approach. Cells were Gram-reaction-negative, non-sporulating,
      non-motile, short rods (0.5-1 * 1-2.5 MUm). By 16S rRNA gene sequences, the
      representative strain, HT073016(T), showed highest similarity values with
      Escherichia fergusonii ATCC 35469(T) at 99.3%, Escherichia coli ATCC 11775(T) at
      99.2%, Escherichia albertii LMG 20976(T) at 98.9%, Escherichia hermannii CIP
      103176(T) at 98.4%, and Escherichia vulneris ATCC 33821(T) at 97.7%. Phylogenetic
      analysis based on the 16S rRNA gene sequences showed that the seven strains
      formed a monophyletic group with five other species of the genus Escherichia.
      Digital DNA-DNA hybridization studies between strain HT073016(T) and five other
      species of the genus Escherichia showed that it shared less than 70% DNA-DNA
      relatedness with all known species of the genus Escherichia, supporting the novel
      species status of the strain. The DNA G+C content of strain HT073016(T) was 53.8
      mol%. On the basis of phenotypic and phylogenetic characteristics, strain
      HT073016(T) and the six other HT073016(T)-like strains were clearly distinct from
      the type strains of other recognized species of the genus Escherichia and
      represent a novel species of the genus Escherichia, for which the name
      Escherichia marmotae sp. nov. is proposed, with HT073016(T) ( = CGMCC 1.12862(T)
      = DSM 28771(T)) as the type strain.

PMID- 25851593
TI  - Pseudomonas endophytica sp. nov., isolated from stem tissue of Solanum tuberosum
      L. in Spain.
AB  - A bacterial strain named BSTT44(T) was isolated in the course of a study of
      endophytic bacteria occurring in stems and roots of potato growing in a soil from
      Salamanca, Spain. The 16S rRNA gene sequence had 99.7% identity with respect to
      that of its closest relative, Pseudomonas psychrophila E-3T, and the next most
      closely related type strains were those of Pseudomonas fragi, with 99.6%
      similarity, Pseudomonas deceptionensis, with 99.2% similarity, and Pseudomonas
      lundensis, with 99.0% similarity; these results indicate that BSTT44(T) should be
      classified within the genus Pseudomonas. Analysis of the housekeeping genes rpoB,
      rpoD and gyrB confirmed its phylogenetic affiliation and showed identities lower
      than 92% in all cases with respect to the above-mentioned closest relatives.
      Cells of the strain bore one polar-subpolar flagellum. The respiratory quinone
      was Q-9.The major fatty acids were C16:0, C18:1omega7c and summed feature 3
      (C16:1omega7c and/or C16:1omega6c). The strain was oxidase-, catalase- and urease
      positive and the arginine dihydrolase system was present, but tests for nitrate
      reduction, beta-galactosidase production and aesculin hydrolysis were negative.
      It could grow at 35  degrees C and at pH 5-9.The DNA G+C content was 60.2 mol%.
      DNA-DNA hybridization results showed less than 48% relatedness with respect to
      the type strains of the four most closely related species. Therefore, the
      combined results of genotypic, phenotypic and chemotaxonomic analyses support the
      classification of strain BSTT44 into a novel species of the genus Pseudomonas,
      for which the name Pseudomonas endophytica sp. nov. is proposed. The type strain
      is BSTT44(T) ( = LMG 28456(T) = CECT 8691(T)).

PMID- 25851595
TI  - Polymer-Derived Ceramic Functionalized MoS2 Composite Paper as a Stable Lithium
      Ion Battery Electrode.
AB  - A facile process is demonstrated for the synthesis of layered SiCN-MoS2 structure
      via pyrolysis of polysilazane functionalized MoS2 flakes. The layered morphology
      and polymer to ceramic transformation on MoS2 surfaces was confirmed by use of
      electron microscopy and spectroscopic techniques. Tested as thick film electrode
      in a Li-ion battery half-cell, SiCN-MoS2 showed the classical three-stage
      reaction with improved cycling stability and capacity retention than neat MoS2.
      Contribution of conversion reaction of Li/MoS2 system on overall capacity was
      marginally affected by the presence of SiCN while Li-irreversibility arising from
      electrolyte decomposition was greatly suppressed. This is understood as one of
      the reasons for decreased first cycle loss and increased capacity retention. SiCN
      MoS2 in the form of self-supporting paper electrode (at 6 mg.cm(-2)) exhibited
      even better performance, regaining initial charge capacity of approximately 530
      mAh.g(-1) when the current density returned to 100 mA.g(-1) after continuous
      cycling at 2400 mA.g(-1) (192 mAh.g(-1)). MoS2 cycled electrode showed mud-cracks
      and film delamination whereas SiCN-MoS2 electrodes were intact and covered with a
      uniform solid electrolyte interphase coating. Taken together, our results suggest
      that molecular level interfacing with precursor-derived SiCN is an effective
      strategy for suppressing the metal-sulfide/electrolyte degradation reaction at
      low discharge potentials. 

PMID- 25851594
TI  - Drug survival and causes of discontinuation of the first anti-TNF in ankylosing
      spondylitis compared with rheumatoid arthritis: analysis from BIOBADABRASIL.
AB  - Treatment survival with biological therapy may be influenced by many factors, and
      it seems to be different among various rheumatic diseases and biological agents.
      The goal of the study was to compare the drug survival and the causes of
      discontinuation of anti-tumoral necrosis factor (anti-TNF) therapy in ankylosing
      spondylitis (AS) with rheumatoid arthritis (RA). Study participants were a cohort
      from the Brazilian Registry of Biological Therapies in Rheumatic Diseases
      (BIOBADABRASIL) between 2008 and 2012. The observation time was up to 4 years
      following the introduction of the first treatment. Gender, age, disease duration,
      disease activity, comorbidities, and concomitant therapies were assessed. A total
      of 1303 patients were included: 372 had AS and 931 had RA in which 38.7 % (n =
      504) used infliximab (IFX), 34.9 % (n = 455) used adalimumab (ADA), and 26.4 % (n
      = 344) used etanercept (ETA). The anti-TNF drug survival of patients with AS was
      63.08 months (confidence interval (CI) 60.24, 65.92) and patients with RA was
      47.5 months (CI 45.65, 49.36). It was significant higher in AS (log-rank; p <=
      0.001). Patients with RA discontinued anti-TNF more than patients with AS when
      adjusted to gender and corticosteroid. The adjHR (95 % CI) was 1.6 (1.14, 2.31).
      Female patients who were also corticosteroid users, but not of advanced age, have
      shown lower survival for both diseases (log-rank, p <= 0.001). The
      discontinuation rate of IFX, but not of ADA or ETA, was significantly higher in
      RA than in SA; HR (95 % CI) was 2.49 (1.46, 4.24). The main causes of
      discontinuation were ineffectiveness and adverse event in both diseases. AS
      patients have better drug survival adjusted to gender, age, and corticosteroid.
      This results appear to be related to the disease mechanism.

PMID- 25851597
TI  - Early Activation of Metalloproteinases after Experimental Myocardial Infarction
      Occurs in Infarct and Non-infarct Zones.
AB  - The collagen matrix of the heart forms a network linking muscle fibers, muscle
      bundles, and intramyocardial blood vessels. Collagen turnover in the heart is
      normally a dynamic process that involves both collagen synthesis and degradation.
      Collagen breakdown generally involves its chemical digestion by matrix
      metalloproteinases (MMPs) which are activated in tissue repair, wound healing,
      and myocardial ischemia. We studied activation of MMPs by zymography in infarct
      (anterolateral wall) and non-infarct (septum) zones of rat hearts following
      coranary artery ligation, as well as in sham operated rats. Rats were sacrificed
      at 30 minutes, 1 hour, 2 hours, 4 hours, and 24 hours post infarction (six hearts
      for each time period). MMP activity was detected at different molecular weights,
      with bands at 54 kDa (MMP-1), 62 kDa (MMP-2), and 92 kDa (MMP-9) being the most
      prominent. MMP activities were indexed by densitometer optical reading. Activity
      was detected as early as 1 hour post infarct in the MI and remote zones at the 54
      kDa (MMP-1) ( p < 0.01) and 62 kDa bands (MMP-2) ( p < 0.001), and at 2 hours
      post infarct in the infarct zone only at 92 kDa (MMP-9) ( p < 0.05). MMPs are
      activated early after infarction both in the infarct and importantly, non-infarct
      zones. This may contribute to collagen breakdown, infarct expansion, and left
      ventricular remodeling, known to occur early after infarction in experimental and
      clinical settings. 

PMID- 25851596
TI  - Identification of Commonly Dysregulated Genes in Non-small-cell Lung Cancer by
      Integrated Analysis of Microarray Data and qRT-PCR Validation.
AB  - BACKGROUND: Non-small-cell lung cancer (NSCLC), the most common lung cancer,
      leads to the largest number of cancer-related deaths worldwide. There are many
      studies to identify the differentially expressed genes (DEGs) between NSCLC and
      normal control (NC) tissues by means of microarray technology. Because of the
      inconsistency of the microarray data sets, we performed an integrated analysis to
      identify DEGs and analyzed their biological function. METHODS AND RESULTS: We
      combined 15 microarray data sets and identified 1063 DEGs between NSCLC and NC
      tissues; in addition, we found that the DEGs were enriched in regulation of cell
      proliferation process and focal adhesion signaling pathway. The protein-protein
      interaction network analysis for the top 20 significantly DEGs revealed that
      CAV1, COL1A1, and ADRB2 were the significant hub proteins. Finally, we employed
      qRT-PCR to validate the meta-analysis approach by determining the expression of
      the top 10 most significantly DEGs and found that the expression of these genes
      were significantly different between tumor and NC tissues, in accordance with the
      results of meta-analysis. CONCLUSION: qRT-PCR results indicated that the meta
      analysis approach in our study was acceptable. Our data suggested that some of
      the DEGs, including MMP12, COL11A1, THBS2, FAP, and CAV1, may participate in the
      pathology of NSCLC and could be applied as potential markers or therapeutic
      targets for NSCLC.

PMID- 25851598
TI  - Causes of isolated aortic insufficiency in an urban population in the 1990s a
      review of 56 surgical pathology cases.
AB  - Until recently, the cause of isolated aortic insufficiency (AI) was usually
      thought to be inflammatory or rheumatic in most cases. However, at our
      institution we have noted a high prevalence of myxomatous degeneration (MD) in
      aortic valves removed for AI. In this study we report anatomic observations on
      valves from 56 consecutive patients with isolated AI undergoing aortic valve
      replacement surgery. Fifty-six consecutive aortic valves removed at our
      institution from 1994 to 1996 for isolated AI and/or aortic aneurysm were
      reviewed. Anatomic features were compared with clinical history and
      echocardiographic data. The anatomic results were also compared to 22 age-matched
      control aortic valves obtained at autopsy. In 13/56 cases (23%), a specific
      valvular cause of AI was determined (infectious endocarditis, seven cases;
      chronic rheumatic disease, four cases; congenital bicuspid valve, two cases). Of
      the remaining (idiopathic) 43 cases, 18 (42%) had severe isolated MD defined as
      >50% expansion of the spongiosa and disruption of the fibrosa by the deposition
      of acid mucopolysaccharides in the absence of severe calcification, fibrosis, or
      other pathologic findings. Only 1/22 aortic valves from the autopsy controls had
      severe MD. Eighteen of the 56 patients also had a clinical history of aortic
      dilatation/aneurysm of which 12 were confirmed to be dilated by echocardiographic
      criteria. Of these 12, five (42%) had MD of the aortic valve only, three (25%)
      had both MD and cystic medial degeneration (CMD) of the aorta, two (17%) had CMD
      of the aorta only, and two (17%) had no specific diagnosis. Isolated MD of the
      aortic valve is the most common cause of isolated AI in our patient population.
      Furthermore, in a subset of non-Marfan's patients with both AI and dilatation of
      the aortic root/aortic aneurysm the incidence of MD is even higher (67%). These
      results suggest that there is overlap between MD and CMD in non-Marfan's patients
      and that both entities may be part of a spectrum of a generalized connective
      tissue disorder. 

PMID- 25851599
TI  - The acute effects of outdoor temperature on blood pressure in a panel of elderly
      hypertensive patients.
AB  - Higher level of blood pressure (BP) in winter than in summer has been observed,
      but the association between temperature and BP and its potential modifiers with
      adjustment of individual confounders and time trends was rarely explored. We
      aimed to investigate the association between outdoor temperature and BP and its
      potential modification factors in a longitudinal panel study in Shanghai, China.
      From January 2011 to December 2012, we scheduled 54 follow-ups for BP
      measurements per subject via home visit every other week for 50 elderly
      hypertensive patients. We applied linear mixed-effect models to analyze the
      association between temperature and BP after controlling for individual
      characteristics, antihypertensive medication, comorbidities, and time trends. We
      evaluated the potential effect modifiers by stratification analyses. For a 1 
      degrees C decrease in the average temperature on concurrent day and previous day,
      systolic BP increased by 0.19 mmHg (95 % confidence interval = 0.06, 0.31) and
      diastolic BP increased by 0.12 mmHg (95 % confidence interval = 0.03, 0.21). The
      effect of temperature on BP was stronger among those with older age, female sex,
      low socioeconomic status, and obese physique. The effect was weak and even null
      for those taking the angiotensin receptor blockers, angiotensin-converting enzyme
      inhibitor, or its combination with calcium antagonists. Further, the effect was
      almost restricted within those having chronic comorbidities. Our results
      demonstrated that an acute decrease in outdoor temperature was significantly
      associated with a rise in BP among elderly hypertensive patients, in Shanghai,
      China. Individual characteristics, antihypertensive medications, and
      comorbidities may modify this effect. 

PMID- 25851600
TI  - Casein kinase 1 controls the activation threshold of an alpha-arrestin by
      multisite phosphorylation of the interdomain hinge.
AB  - alpha-Arrestins play a key role as trafficking adaptors in both yeast and
      mammals. The yeast Rim8/Art9 alpha-arrestin mediates the recruitment of endosomal
      sorting complex required for transport (ESCRT) to the seven-transmembrane protein
      Rim21 in the ambient pH signaling RIM pathway. ESCRT is believed to function as a
      signaling platform that enables the proteolytic activation of the Rim101
      transcription factor upon external alkalization. Here we provide evidence that
      the pH signal promotes the stable association of Rim8 with Rim21 at the plasma
      membrane. We show that Rim8 is phosphorylated in a pH-independent but Rim21
      dependent manner by the plasma membrane-associated casein kinase 1 (CK1). We
      further show that this process involves a cascade of phosphorylation events
      within the hinge region connecting the arrestin domains. Strikingly, loss of
      casein kinase 1 activity causes constitutive activation of the RIM pathway, and,
      accordingly, pH signaling is activated in a phosphodeficient Rim8 mutant and
      impaired in the corresponding phosphomimetic mutant. Our results indicate that
      Rim8 phosphorylation prevents its accumulation at the plasma membrane at acidic
      pH and thereby inhibits RIM signaling. These findings support a model in which
      CK1-mediated phosphorylation of Rim8 contributes to setting a signaling threshold
      required to inhibit the RIM pathway at acidic pH. 

PMID- 25851601
TI  - The RhoGEF DOCK10 is essential for dendritic spine morphogenesis.
AB  - By regulating actin cytoskeleton dynamics, Rho GTPases and their activators
      RhoGEFs are implicated in various aspects of neuronal differentiation, including
      dendritogenesis and synaptogenesis. Purkinje cells (PCs) of the cerebellum, by
      developing spectacular dendrites covered with spines, represent an attractive
      model system in which to decipher the molecular signaling underlying these
      processes. To identify novel regulators of dendritic spine morphogenesis among
      members of the poorly characterized DOCK family of RhoGEFs, we performed gene
      expression profiling of fluorescence-activated cell sorting (FACS)-purified
      murine PCs at various stages of their postnatal differentiation. We found a
      strong increase in the expression of the Cdc42-specific GEF DOCK10. Depleting
      DOCK10 in organotypic cerebellar cultures resulted in dramatic dendritic spine
      defects in PCs. Accordingly, in mouse hippocampal neurons, depletion of DOCK10 or
      expression of a DOCK10 GEF-dead mutant led to a strong decrease in spine density
      and size. Conversely, overexpression of DOCK10 led to increased spine formation.
      We show that DOCK10 function in spinogenesis is mediated mainly by Cdc42 and its
      downstream effectors N-WASP and PAK3, although DOCK10 is also able to activate
      Rac1. Our global approach thus identifies an unprecedented function for DOCK10 as
      a novel regulator of dendritic spine morphogenesis via a Cdc42-mediated pathway. 

PMID- 25851602
TI  - Asymmetric formation of coated pits on dorsal and ventral surfaces at the leading
      edges of motile cells and on protrusions of immobile cells.
AB  - Clathrin/AP2-coated vesicles are the principal endocytic carriers originating at
      the plasma membrane. In the experiments reported here, we used spinning-disk
      confocal and lattice light-sheet microscopy to study the assembly dynamics of
      coated pits on the dorsal and ventral membranes of migrating U373 glioblastoma
      cells stably expressing AP2 tagged with enhanced green fluorescence (AP2-EGFP)
      and on lateral protrusions from immobile SUM159 breast carcinoma cells, gene
      edited to express AP2-EGFP. On U373 cells, coated pits initiated on the dorsal
      membrane at the front of the lamellipodium and at the approximate boundary
      between the lamellipodium and lamella and continued to grow as they were swept
      back toward the cell body; coated pits were absent from the corresponding ventral
      membrane. We observed a similar dorsal/ventral asymmetry on membrane protrusions
      from SUM159 cells. Stationary coated pits formed and budded on the remainder of
      the dorsal and ventral surfaces of both types of cells. These observations
      support a previously proposed model that invokes net membrane deposition at the
      leading edge due to an imbalance between the endocytic and exocytic membrane flow
      at the front of a migrating cell. 

PMID- 25851603
TI  - Sorting nexin 27 regulates basal and stimulated brush border trafficking of NHE3.
AB  - Sorting nexin 27 (SNX27) contains a PDZ domain that is phylogenetically related
      to the PDZ domains of the NHERF proteins. Studies on nonepithelial cells have
      shown that this protein is located in endosomes, where it regulates trafficking
      of cargo proteins in a PDZ domain-dependent manner. However, the role of SNX27 in
      trafficking of cargo proteins in epithelial cells has not been adequately
      explored. Here we show that SNX27 directly interacts with NHE3 (C-terminus)
      primarily through the SNX27 PDZ domain. A combination of knockdown and
      reconstitution experiments with wild type and a PDZ domain mutant (GYGF -> GAGA)
      of SNX27 demonstrate that the PDZ domain of SNX27 is required to maintain basal
      NHE3 activity and surface expression of NHE3 in polarized epithelial cells.
      Biotinylation-based recycling and degradation studies in intestinal epithelial
      cells show that SNX27 is required for the exocytosis (not endocytosis) of NHE3
      from early endosome to plasma membrane. SNX27 is also required to regulate the
      retention of NHE3 on the plasma membrane. The findings of the present study
      extend our understanding of PDZ-mediated recycling of cargo proteins from
      endosome to plasma membrane in epithelial cells. 

PMID- 25851604
TI  - The human 18S rRNA base methyltransferases DIMT1L and WBSCR22-TRMT112 but not
      rRNA modification are required for ribosome biogenesis.
AB  - At the heart of the ribosome lie rRNAs, whose catalytic function in translation
      is subtly modulated by posttranscriptional modifications. In the small ribosomal
      subunit of budding yeast, on the 18S rRNA, two adjacent adenosines (A1781/A1782)
      are N(6)-dimethylated by Dim1 near the decoding site, and one guanosine (G1575)
      is N(7)-methylated by Bud23-Trm112 at a ridge between the P- and E-site tRNAs.
      Here we establish human DIMT1L and WBSCR22-TRMT112 as the functional homologues
      of yeast Dim1 and Bud23-Trm112. We report that these enzymes are required for
      distinct pre-rRNA processing reactions leading to synthesis of 18S rRNA, and we
      demonstrate that in human cells, as in budding yeast, ribosome biogenesis
      requires the presence of the modification enzyme rather than its RNA-modifying
      catalytic activity. We conclude that a quality control mechanism has been
      conserved from yeast to human by which binding of a methyltransferase to nascent
      pre-rRNAs is a prerequisite to processing, so that all cleaved RNAs are committed
      to faithful modification. We further report that 18S rRNA dimethylation is
      nuclear in human cells, in contrast to yeast, where it is cytoplasmic. Yeast and
      human ribosome biogenesis thus have both conserved and distinctive features. 

PMID- 25851605
TI  - Cyclin-dependent kinase 5 acts as a critical determinant of AKT-dependent
      proliferation and regulates differential gene expression by the androgen receptor
      in prostate cancer cells.
AB  - Contrary to cell cycle-associated cyclin-dependent kinases, CDK5 is best known
      for its regulation of signaling processes in differentiated cells and its
      destructive activation in Alzheimer's disease. Recently, CDK5 has been implicated
      in a number of different cancers, but how it is able to stimulate cancer-related
      signaling pathways remains enigmatic. Our goal was to study the cancer-promoting
      mechanisms of CDK5 in prostate cancer. We observed that CDK5 is necessary for
      proliferation of several prostate cancer cell lines. Correspondingly, there was
      considerable growth promotion when CDK5 was overexpressed. When examining the
      reasons for the altered proliferation effects, we observed that CDK5
      phosphorylates S308 on the androgen receptor (AR), resulting in its stabilization
      and differential expression of AR target genes including several growth-priming
      transcription factors. However, the amplified cell growth was found to be
      separated from AR signaling, further corroborated by CDK5-dependent proliferation
      of AR null cells. Instead, we found that the key growth-promoting effect was due
      to specific CDK5-mediated AKT activation. Down-regulation of CDK5 repressed AKT
      phosphorylation by altering its intracellular localization, immediately followed
      by prominent cell cycle inhibition. Taken together, these results suggest that
      CDK5 acts as a crucial signaling hub in prostate cancer cells by controlling
      androgen responses through AR, maintaining and accelerating cell proliferation
      through AKT activation, and releasing cell cycle breaks.

PMID- 25851607
TI  - Cognitive impairment and potential biological and psychological correlates of
      neuropsychological performance in recently orchiectomized testicular cancer
      patients.
AB  - OBJECTIVE: The aim of this study was to determine the prevalence of cognitive
      impairment (CI) in newly diagnosed and orchiectomized testicular cancer (TC)
      patients prior to systemic treatment, and to explore biological and psychological
      correlates. METHODS: Sixty-six TC patients were compared with 25 healthy men on
      neuropsychological tests and a measure of cognitive complaints. CI status and a
      global composite score (representing overall neuropsychological performance) were
      calculated for each participant. Possible psychological (depression, anxiety,
      stress, and post-traumatic stress symptoms) and biological (cortisol, IL-6, TNF
      alpha, and CRP) correlates and predictors of patients' cognitive functioning were
      explored. RESULTS: TC patients had lower scores on 6 out of 11 neuropsychological
      outcomes (p < 0.01) in processing speed, attention, and working memory, verbal
      learning and memory, and verbal fluency. Prevalence of CI among TC patients was
      58%, significantly exceeding the frequency in healthy men (p < 0.01). Patients'
      cortisol levels predicted overall neuropsychological performance (p = 0.04).
      Cognitive complaints were associated with IL-6 (p = 0.02) and all psychological
      distress measures (p < 0.001). CONCLUSIONS: The prevalence of CI in recently
      orchiectomized TC patients was unexpectedly high with patients performing more
      poorly than healthy controls on a majority of neuropsychological outcomes.
      Cortisol is a potential predictor of neuropsychological performance in TC
      patients prior to cytotoxic treatment.

PMID- 25851606
TI  - Twitchin kinase interacts with MAPKAP kinase 2 in Caenorhabditis elegans striated
      muscle.
AB  - In Caenorhabditis elegans, twitchin is a giant polypeptide located in muscle A
      bands. The protein kinase of twitchin is autoinhibited by 45 residues upstream
      (NL) and 60 residues downstream (CRD) of the kinase catalytic core. Molecular
      dynamics simulation on a twitchin fragment revealed that the NL is released by
      pulling force. However, it is unclear how the CRD is removed. To identify
      proteins that may remove the CRD, we performed a yeast two-hybrid screen using
      twitchin kinase as bait. One interactor is MAK-1, C. elegans orthologue of MAPKAP
      kinase 2. MAPKAP kinase 2 is phosphorylated and activated by p38 MAP kinase. We
      demonstrate that the CRD of twitchin is important for binding to MAK-1. mak-1 is
      expressed in nematode body wall muscle, and antibodies to MAK-1 localize between
      and around Z-disk analogues and to the edge of A-bands. Whereas unc-22 mutants
      are completely resistant, mak-1 mutants are partially resistant to nicotine. MAK
      1 can phosphorylate twitchin NL-Kin-CRD in vitro. Genetic data suggest the
      involvement of two other mak-1 paralogues and two orthologues of p38 MAP kinase.
      These results suggest that MAK-1 is an activator of twitchin kinase and that the
      p38 MAP kinase pathway may be involved in the regulation of twitchin. 

PMID- 25851608
TI  - Coping with burns: the role of coping self-efficacy in the recovery from
      traumatic stress following burn injuries.
AB  - We conducted a three-wave prospective study among patients with burns (N = 178)
      to examine the prospective influence of coping self-efficacy (CSE) perceptions on
      trajectories of posttraumatic stress symptoms in the first 12 months after burn
      injuries. Using linear growth curve modeling, we corrected for demographics, the
      number of surgeries during initial admittance, trait coping styles, and changing
      levels of health-related quality of life. CSE during initial admission was by far
      the strongest predictor of both initial PTSD symptoms and degree of symptom
      change with higher CSE levels associated with lower initial symptoms and a
      steeper decline of symptoms over time. Of the other variables only avoidant
      coping was associated with higher initial symptom levels, and only emotional
      expression associated with greater rate of recovery. Current findings suggest
      that CSE plays a pivotal role in recovery from posttraumatic stress after a burn
      injury, even when the role of burn-related impairments is taken into
      consideration. Implications of findings are discussed.

PMID- 25851609
TI  - Exercise habit formation in new gym members: a longitudinal study.
AB  - Reasoned action approaches have primarily been applied to understand exercise
      behaviour for the past three decades, yet emerging findings in unconscious and
      Dual Process research show that behavior may also be predicted by automatic
      processes such as habit. The purpose of this study was to: (1) investigate the
      behavioral requirements for exercise habit formation, (2) how Dual Process
      approach predicts behaviour, and (3) what predicts habit by testing a model
      (Lally and Gardner in Health Psychol Rev 7:S137-S158, 2013). Participants (n =
      111) were new gym members who completed surveys across 12 weeks. It was found
      that exercising for at least four bouts per week for 6 weeks was the minimum
      requirement to establish an exercise habit. Dual Process analysis using Linear
      Mixed Models (LMM) revealed habit and intention to be parallel predictors of
      exercise behavior in the trajectory analysis. Finally, the habit antecedent model
      in LLM showed that consistency (beta = .21), low behavioral complexity (beta =
      .19), environment (beta = .17) and affective judgments (beta = .13) all
      significantly (p < .05) predicted changes in habit formation over time. Trainers
      should keep exercises fun and simple for new clients and focus on consistency
      which could lead to habit formation in nearly 6 weeks.

PMID- 25851610
TI  - Affective associations and cognitive beliefs relate to individuals' decisions to
      perform testicular or breast self-exams.
AB  - Affective associations with behavioral practices play an important role in
      individuals' uptake of a variety of health behaviors. Most work has looked at
      individual behavioral practices with a direct impact on health; because screening
      behaviors are conceptually distinct from such behaviors, it is important to
      examine the interplay of affect and cognition in screening decision making. The
      current research explored affective and cognitive predictors of testicular and
      breast self-examination behavior. Young adult participants (N = 184) reported
      cognitive beliefs and affective associations with testicular self-exam behavior
      (male participants) and breast self-exam behavior (female participants) and
      reported their own current screening behavior. In univariable models, affective
      associations were related to screening behavior for both testicular self-exams
      and breast self-exams. When examining affective associations and cognitive
      beliefs as simultaneous predictors, affective associations (but not cognitive
      beliefs) predicted testicular self-exams, and neither affective associations nor
      cognitive beliefs were uniquely related to breast self-exams. Moreover, for
      testicular self-exams, affective associations mediated the relation between
      cognitive beliefs and screening behavior; no mediation was present for breast
      self-exam behavior. These findings suggest three potential outcomes: first, that
      greater consideration of affective associations in testicular self-exam screening
      decisions may be warranted; second, that breast and testicular self-exams may
      have different antecedents; and third, that incorporation of affective factors in
      intervention design might have merit for increasing engagement in some cancer
      screening behaviors.

PMID- 25851611
TI  - Effect of animal mixing as a stressor on biomarkers of autophagy and oxidative
      stress during pig muscle maturation.
AB  - The objective of this work was to study the postmortem evolution of potential
      biomarkers of autophagy (Beclin 1, LC3-II/LC3-I ratio) and oxidative stress
      (total antioxidant activity, TAA; superoxide dismutase activity, SOD and catalase
      activity, CAT) in the Longissimus dorsi muscle of entire male ((Large
      White*Landrace)*Duroc) pigs subjected to different management treatments that may
      promote stress, such as mixing unfamiliar animals at the farm and/or during
      transport and lairage before slaughter. During the rearing period at the farm,
      five animals were never mixed after the initial formation of the experimental
      groups (unmixed group at the farm, UF), whereas 10 animals were subjected to a
      common routine of being mixed with unfamiliar animals (mixed group at the farm,
      MF). Furthermore, two different treatments were used during the transport and
      lairage before slaughter: 10 pigs were not mixed (unmixed group during transport
      and lairage, UTL), whereas five pigs were mixed with unfamiliar animals on the
      lorry and during lairage (mixed group during transport and lairage, MTL). These
      mixing treatments were then combined into three pre-slaughter treatments -
      namely, UF-UTL, MF-UTL and MF-MTL. The results show that MF-UTL and MF-MTL
      increased significantly the muscle antioxidant defense (TAA, SOD and CAT) at
      short postmortem times (4 and 8 h; P<0.001), followed by an earlier depletion of
      the antioxidant activity at 24 h postmortem (P<0.05). We also found that mixing
      unfamiliar animals, both at the farm and during transport and lairage, triggers
      postmortem muscle autophagy, which showed an earlier activation (higher
      expression of Beclin 1 and LC3-II/LC3-I ratio at 4 h postmortem followed by a
      decreasing pattern of this ratio along first 24 h postmortem) in the muscle
      tissues of animals from the MF-UTL and MF-MTL groups, as an adaptive strategy of
      the muscle cells for counteracting induced stress. From these results, we propose
      that monitoring the evolution of the main biomarkers of autophagy (Beclin 1, LC3
      II/LC3-I ratio) and muscle antioxidant defense (TAA, SOD, CAT) in the muscle
      tissue within the first 24 h postmortem may help the detection of animal stress
      and its potential effect on the postmortem muscle metabolism. 

PMID- 25851612
TI  - Dichorionic triplet pregnancies: risk of miscarriage and severe preterm delivery
      with fetal reduction versus expectant management. Outcomes of a cohort study and
      systematic review.
AB  - BACKGROUND: In trichorionic pregnancies, fetal reduction from three to two lowers
      the risk of severe preterm delivery, but provides no advantage in survival.
      Similar data for dichorionic triamniotic (DCTA) triplets is not readily
      available. OBJECTIVES: To document the natural history of DCTA triplets and the
      effect of reduction on the risk of miscarriage and severe preterm delivery,
      compared with expectant management. SEARCH STRATEGY: Systematic search on
      MEDLINE, EMBASE, and the Cochrane Library. SELECTION CRITERIA: DCTA triplets with
      three live fetuses at 8-14 weeks of gestation, outcome data with expectant
      management and/or reduction, miscarriage before 24 weeks of gestation and/or
      severe preterm delivery before 32-33 weeks of gestation. DATA COLLECTION AND
      ANALYSIS: Five studies were included. Data from these were combined with data
      from three centres. MAIN RESULTS: There were 331 DCTA triplets. The miscarriage
      rate was 8.9% (95% CI 5.8-13.3%) and the severe preterm delivery rate was 33.3%
      (95% CI 27.5-39.7%), with expectant management. The miscarriage rate was 14.5%
      (95% CI 7.6-26.2%) with a reduction of the monochorionic pair, 8.8% (95% CI 3.0
      23.0%) with a reduction of one fetus of the monochorionic pair, and 23.5% (9.6
      47.3%) with a reduction of the fetus with a separate placenta. Severe preterm
      delivery rates were 5.5% (95% CI 1.9-14-9%), 11.8% (95% CI 4.7-26.6%), and 17.6%
      (95% CI 6.2-41.0%), respectively. CONCLUSIONS: In DCTA triplets, expectant
      management is a reasonable choice when the top priority is a liveborn infant.
      Where the priority is to minimise severe preterm delivery, the most advisable
      option is fetal reduction. Further studies are needed to clarify which particular
      technique is advisable to optimise the outcome.

PMID- 25851613
TI  - The cytosolic branched-chain aminotransferases of Arabidopsis thaliana influence
      methionine supply, salvage and glucosinolate metabolism.
AB  - Arabidopsis thaliana possesses six branched-chain aminotransferases (BCAT1-6).
      Previous studies revealed that some members of this protein family are involved
      in the biosynthesis of branched-chain amino acids and/or in the Met chain
      elongation pathway, the initial steps towards the biosynthesis of Met-derived
      glucosinolates. We now analyzed branched-chain aminotransferase 6 (BCAT6). In
      vivo GFP-tagging experiments strongly suggest this enzyme to be localized to the
      cytosol. Substrate specificity assays performed with recombinant enzyme revealed
      that BCAT6 transaminates Val, Leu and Ile as well as the corresponding 2-oxo
      acids but also transaminates Met and its cognate ketoacid 4-methyl-2
      oxobutanoate. We established single (bcat6-1), double (bcat4-2/bcat6-1) and
      triple (bcat3-1/bcat4-2/bcat6-1) mutants involving BCAT6 with the latter
      exhibiting a clear macroscopic phenotype with smaller plants and abnormal leaf
      morphology. Metabolite profiling of these mutants demonstrated that BCAT6 can
      contribute to Met chain elongation with the triple mutant line lacking BCAT3, 4
      and 6 showing a dramatic reduction of Met-derived glucosinolate species down to
      32 and 14% of wild-type levels in plant foliage and seeds, respectively. This
      drop in glucosinolate levels is accompanied by a 46-fold increase of free Met,
      demonstrating the important role of the three branched-chain aminotransferases in
      converting Met to its 2-oxo acid for glucosinolate chain elongation. In addition,
      we determined the relative amounts of 5'-deoxy-5'-methylthioadenosine, an
      intermediate of the Met recycling pathway. This metabolite accumulated to
      relative high amounts in the absence of the cytosolic BCAT4 and BCAT6, suggesting
      that cytosolic Met salvage also contributes to the biosynthesis of
      glucosinolates.

PMID- 25851614
TI  - Discovery, evaluation and distribution of haplotypes and new alleles of the
      Photoperiod-A1 gene in wheat.
AB  - Photoperiod response in wheat is determined to a large extent by the homoeologous
      series of Photoperiod 1 (Ppd1) genes. In this study, Ppd-A1 genomic sequences
      from the 5' UTR and promoter region were analysed in 104 accessions of six
      tetraploid wheat species (Triticum dicoccoides, T. dicoccum, T. turgidum, T.
      polonicum, T. carthlicum, T. durum) and 102 accessions of six hexaploid wheat
      species (T. aestivum, T. compactum, T. sphaerococcum, T. spelta, T. macha, T.
      vavilovii). This data was supplemented with in silico analysis of publicly
      available sequences from 46 to 193 accessions of diploid and tetraploid wheat,
      respectively. Analysis of a region of the Ppd-A1 promoter identified thirteen
      haplotypes, which were divided in two haplogroups. Distribution of the Ppd-A1
      haplogroups and haplotypes in wheat species, and their geographical distributions
      were analysed. Polymerase chain reaction combined with a heteroduplex mobility
      assay was subsequently used to efficiently discriminate between Ppd-A1 alleles,
      allowing identification of the Ppd-A1b haplotypes and haplogroups. The causes of
      anomalous migration of Ppd-A1 heteroduplexes in gels were found to be the
      localization of mismatches relative to the center of fragment, the cumulative
      effect of neighbouring polymorphic sites, and the location of mismatches within
      A/T-tracts. Analysis of the Ppd-A1 5' UTR in hexaploid wheat revealed a novel
      mutation within the "photoperiod critical" region in a subset of T. compactum
      accessions. This putative photoperiod insensitive allele (designated Ppd-A1a.4)
      includes a 684 bp deletion which spans region in common with deletions previously
      identified in other photoperiod insensitive Ppd1 alleles. 

PMID- 25851615
TI  - Familial risk for distress and fear disorders and emotional reactivity in
      adolescence: an event-related potential investigation.
AB  - BACKGROUND: The late positive potential (LPP) is an event-related potential
      component that is sensitive to the motivational salience of stimuli. Children
      with a parental history of depression, an indicator of risk, have been found to
      exhibit an attenuated LPP to emotional stimuli. Research on depressive and
      anxiety disorders has organized these conditions into two empirical classes:
      distress and fear disorders. The present study examined whether parental history
      of distress and fear disorders was associated with the LPP to emotional stimuli
      in a large sample of adolescent girls. METHOD: The sample of 550 girls (ages 13.5
      15.5 years) with no lifetime history of depression completed an emotional picture
      viewing task and the LPP was measured in response to neutral, pleasant and
      unpleasant pictures. Parental lifetime history of psychopathology was determined
      via a semi-structured diagnostic interview with a biological parent, and
      confirmatory factor analysis was used to model distress and fear dimensions.
      RESULTS: Parental distress risk was associated with an attenuated LPP to all
      stimuli. In contrast, parental fear risk was associated with an enhanced LPP to
      unpleasant pictures but was unrelated to the LPP to neutral and pleasant
      pictures. Furthermore, these results were independent of the adolescent girls'
      current depression and anxiety symptoms and pubertal status. CONCLUSIONS: The
      present study demonstrates that familial risk for distress and fear disorders may
      have unique profiles in terms of electrocortical measures of emotional
      information processing. This study is also one of the first to investigate
      emotional/motivational processes underlying the distress and fear disorder
      dimensions.

PMID- 25851616
TI  - Cost effectiveness of paliperidone palmitate versus oral antipsychotics in
      patients with schizophrenia and a history of criminal justice involvement.
AB  - OBJECTIVE: Conduct a cost effectiveness analysis for the Paliperidone palmitate
      Research In Demonstrating Effectiveness (PRIDE) trial. RESEARCH DESIGN AND
      METHODS: PRIDE was a 15 month, prospective, randomized, open-label study in which
      once monthly paliperidone palmitate significantly delayed the time to first
      treatment failure (healthcare or criminal justice system [HC/CJS] events) versus
      oral antipsychotics in recently incarcerated adults with schizophrenia. The
      present analysis used a state government perspective and HC/CJS event data that
      were collected on a resource use questionnaire (RUQ) every 3 months. MAIN OUTCOME
      MEASURES: Since cost information was not collected in the trial, cost estimates
      from published literature and an analysis of multistate Medicaid data for CJS and
      HC events, respectively, were applied to RUQ event data. Effectiveness and costs
      were adjusted to 456 days (trial duration). Incremental cost effectiveness was
      calculated as the adjusted cost difference divided by the adjusted effectiveness
      difference. RESULTS: Adjusted costs (in US dollars) in the paliperidone palmitate
      group (n = 198) and the oral antipsychotic group (n = 193), respectively, were:
      non-drug costs $22,331 and $25,027; drug costs $18,592 and $7833; and total costs
      $40,923 and $32,860. Adjusted effectiveness differences and corresponding
      incremental cost effectiveness per event avoided (in parentheses) for
      paliperidone palmitate versus oral antipsychotics were as follows: 0.33 fewer CJS
      events ($24,409), 0.13 fewer psychiatric hospitalizations ($60,484), 0.46 fewer
      psychiatric hospitalizations or CJS events combined ($17,391), and 0.30 fewer
      incarcerations ($26,754). CONCLUSIONS: Costs for HC/CJS events avoided offset 25%
      of the greater drug cost for the paliperidone palmitate versus oral antipsychotic
      treatment group in this vulnerable population. Use of a recall-dependent RUQ for
      event rates and cost estimates instead of actual costs are potential limitations
      and may make the results conservative from a state government perspective.
      Indirect costs are likely to be substantial for this population, but were not
      considered in the analysis.

PMID- 25851617
TI  - De novo exon 1 deletion of AUTS2 gene in a patient with autism spectrum disorder
      and developmental delay: a case report and a brief literature review.
AB  - Exonic deletions disrupting the autism susceptibility candidate 2 (AUTS2) gene
      have been demonstrated as causal variants leading to neurodevelopmental disorders
      (NDDs) such as autism spectrum disorder (ASD) and developmental delay (DD). Here,
      we report on 830 kb de novo deletion at chromosome 7q11.22 in a 4-year-old male
      patient with ASD and DD. This deletion disrupts the promoter region and exon 1 of
      AUTS2, potentially leading to complete haploinsuffiency of the gene. In addition,
      we discuss the clinical presentation of the de novo deletion in the light of the
      previous studies describing deletions of AUTS2 in NDDs.

PMID- 25851618
TI  - Population structure of humpback whales in the western and central South Pacific
      Ocean as determined by vocal exchange among populations.
AB  - For cetaceans, population structure is traditionally determined by molecular
      genetics or photographically identified individuals. Acoustic data, however, has
      provided information on movement and population structure with less effort and
      cost than traditional methods in an array of taxa. Male humpback whales
      (Megaptera novaeangliae) produce a continually evolving vocal sexual display, or
      song, that is similar among all males in a population. The rapid cultural
      transmission (the transfer of information or behavior between conspecifics
      through social learning) of different versions of this display between distinct
      but interconnected populations in the western and central South Pacific region
      presents a unique way to investigate population structure based on the movement
      dynamics of a song (acoustic) display. Using 11 years of data, we investigated an
      acoustically based population structure for the region by comparing stereotyped
      song sequences among populations and years. We used the Levenshtein distance
      technique to group previously defined populations into (vocally based) clusters
      based on the overall similarity of their song display in space and time. We
      identified the following distinct vocal clusters: western cluster, 1 population
      off eastern Australia; central cluster, populations around New Caledonia, Tonga,
      and American Samoa; and eastern region, either a single cluster or 2 clusters,
      one around the Cook Islands and the other off French Polynesia. These results are
      consistent with the hypothesis that each breeding aggregation represents a
      distinct population (each occupied a single, terminal node) in a metapopulation,
      similar to the current understanding of population structure based on genetic and
      photo-identification studies. However, the central vocal cluster had higher
      levels of song-sharing among populations than the other clusters, indicating that
      levels of vocal connectivity varied within the region. Our results demonstrate
      the utility and value of using culturally transmitted vocal patterns as a way of
      defining connectivity to infer population structure. We suggest vocal patterns be
      incorporated by the International Whaling Commission in conjunction with
      traditional methods in the assessment of structure. 

PMID- 25851619
TI  - Selective disruption of heparin and antithrombin-mediated regulation of human
      factor IX.
AB  - BACKGROUND: Interaction with antithrombin and heparin regulates distribution,
      activity, and clearance of factor IXa (FIXa). Hemophilia B prophylaxis targets
      plasma FIX levels > 1% but neglects extravascular FIX, which colocalizes with
      antithrombin-heparan sulfate. OBJECTIVE: Combined mutagenesis of FIX was
      undertaken to selectively disrupt heparin- and antithrombin-mediated regulation
      of the protease. METHODS: Human FIX alanine substitutions in the heparin (K126A
      and K132A) and antithrombin (R150A) exosites were characterized with regard to
      coagulant activity, plasma thrombin generation, antithrombin inhibition, and
      plasma half-life. RESULTS: Single or combined (K126A/R150A or K132A/R150A)
      exosite mutations variably reduced coagulant activity relative to wild-type (WT)
      for FIX (27-91%) and FIXa (25-91%). Double mutation in the heparin exosite
      (K126A/K132A and K126A/K132A/R150A) markedly reduced coagulant activity (7-21%)
      and plasma TG. In contrast to coagulant activity, FIX K126A (1.8-fold), R150 (1.6
      fold), and K132A/R150A (1.3-fold) supported increased tissue factor-initiated
      plasma TG, while FIX K132A and K126A/R150A were similar to WT. FIXa K126A/R150A
      and K132A/R150A (1.5-fold) demonstrated significantly increased FIXa-initiated
      TG, while FIXa K132A, R150A, and K126A (0.8-0.9-fold) were similar to WT. Dual
      mutations in the heparin exosite or combined mutations in both exosites
      synergistically reduced the inhibition rate for antithrombin-heparin. The half
      life of FIXa WT in FIX-deficient plasma was remarkably lengthy (40.9 +/-1.4 min)
      and further prolonged for FIXa R150A, K126A/R150A, and K132A/R150A (> 2 h).
      CONCLUSION: Selective disruption of exosite-mediated regulation by heparin and
      antithrombin can be achieved with preserved or enhanced thrombin generation
      capacity. These proteins should demonstrate enhanced therapeutic efficacy for
      hemophilia B.

PMID- 25851620
TI  - Resetting of a Supraventricular Tachycardia by a Ventricular Premature Beat. What
      is the Mechanism?

PMID- 25851622
TI  - A general salt-templating method to fabricate vertically aligned graphitic carbon
      nanosheets and their metal carbide hybrids for superior lithium ion batteries and
      water splitting.
AB  - The synthesis of vertically aligned functional graphitic carbon nanosheets (CNS)
      is challenging. Herein, we demonstrate a general approach for the fabrication of
      vertically aligned CNS and metal carbide@CNS composites via a facile salt
      templating induced self-assembly. The resulting vertically aligned CNS and metal
      carbide@CNS structures possess ultrathin walls, good electrical conductivity,
      strong adhesion, excellent structural robustness, and small particle size. In
      electrochemical energy conversion and storage such unique features are favorable
      for providing efficient mass transport as well as a large and accessible
      electroactive surface. The materials were tested as electrodes in a lithium ion
      battery and in electrochemical water splitting. The vertically aligned nanosheets
      exhibit remarkable lithium ion storage properties and, concurrently, excellent
      properties as electrocatalysts for hydrogen evolution. 

PMID- 25851623
TI  - No association between iron status and self-reported health-related quality of
      life in 16,375 Danish blood donors: results from the Danish Blood Donor Study.
AB  - BACKGROUND: Health-related quality of life (HRQL) represents people's subjective
      assessment of their mental and physical well-being. HRQL is highly predictive of
      future health. The effect of iron deficiency without anemia induced by blood
      donation on HRQL is presently unknown. The aim was to explore the relationship
      between iron status and self-reported mental component score (MCS; SF-12) and
      physical component score (PCS; SF-12) in Danish blood donors. STUDY DESIGN AND
      METHODS: Complete relevant data, including the 12-item short-form health survey
      (SF-12), plasma ferritin levels, age, body mass index, smoking status, C-reactive
      protein levels, number of donations in the previous 3 years, and PCS and MCS,
      were available for 8692 men and 7683 women enrolled from March 1, 2010, to
      December 31, 2010. Multivariable linear and logistic (cutoff at the 10th
      percentile) regression analyses were used to assess the relationship between iron
      deficiency (ferritin < 15 ng/mL) and MCS and PCS, respectively. Analyses were
      performed separately for men and women. RESULTS: There was no significant
      relationship between iron deficiency and self-reported mental or physical health.
      CONCLUSION: This study found no association between iron stores and self-reported
      HRQL among Danish blood donors.

PMID- 25851624
TI  - Comparative effects of PEG-containing liposomal formulations on in vivo
      pharmacokinetics of streptokinase.
AB  - Streptokinase (SK) is an effective thrombolytic agent, but it has a short half
      life due to its rapid elimination from the body. In this study, we prepared and
      evaluated polyethyleneglycol (PEG)-based liposomal formulations (PEG-liposomes)
      containing SK with a view toward prolonging its circulatory half-life. SK-bearing
      liposomes (SK-liposomes) were prepared using freeze-thaw method after film
      hydration and extrusion techniques, composed of phosphatidylcholine [egg
      phosphatidylcholine (EPC), dipalmitoyl PC, or distearoyl PC], cholesterol and
      cholesterol-3-sulfate with or without PEG. Their physicochemical properties were
      characterized by the measurement of size and zeta potential and incorporation
      efficiency. SK-liposomal formulations were applied to rats through a femoral vein
      via intravenous administration to compare the effects of liposomal delivery and
      PEG on the half-life of SK in blood. Free SK was used as a control. SK activities
      in plasma were measured to estimate the amidolytic activity of SK-plasminogen
      complex after rupturing liposomes with Triton X-100. Pharmacokinetic parameters
      were obtained from SK activity-time profiles. The SK-liposomes had a homogenous
      distribution of negatively charged nanoparticles at the range of 10-33% of the
      incorporation efficiencies of SK. Among the SK-liposomes, SK-EPC- and SK-EPC/PEG
      liposomes had injectable diameters (<200 nm). SK was administered as free SK, SK
      EPC-liposomes, or SK-EPC/PEG-liposomes for in vivo study. SK-EPC/PEG-liposomes
      had significantly greater the t(1/2), AUC(infinity) and MRT values of SK than SK
      alone or SK-EPC-liposomes. These findings suggest that PEG-liposomal
      incorporation of SK enhances thrombolytic activity in vivo, and that such
      liposomes can be utilized to enhance the pharmacokinetic profiles of other
      therapeutic proteins with a short biological half-life.

PMID- 25851625
TI  - Self-reported symptoms of attention-deficit/hyperactivity disorder: rate of
      endorsement and association with neuropsychological performance in an adult
      psychiatric sample.
AB  - The lack of specificity of attention-deficit/hyperactivity disorder (ADHD)
      symptoms represents a diagnostic challenge, especially when assessing psychiatric
      patients reporting a wide range of complaints. Rate of endorsement of ADHD
      symptoms, and their association with neuropsychological performance, was examined
      in a psychiatric sample of 71 adults, who had been referred for a
      neuropsychological evaluation. Patients completed two self-report measures of
      ADHD symptoms, the ADHD Self-Report Scale (ADHD-SR) and the Wender Utah Rating
      Scale-Short Form, as well as measures of attention, executive functioning,
      visuoconstructional ability, and verbal learning and memory. On the ADHD-SR,
      74.6% of the sample met the cutoff for inattention or hyperactivity, while 81.7%
      met the cutoff for impulsivity. Neuropsychological performance was weakly
      associated with self-reported symptoms. Our results suggest that psychiatric
      patients commonly report symptoms of inattention, hyperactivity, and impulsivity.
      Assessment utilizing multiple sources is necessary to confirm whether self
      reported symptoms are indicative of ADHD or reflect other causes. 

PMID- 25851626
TI  - Circulating tumor DNA as an early marker of therapeutic response in patients with
      metastatic colorectal cancer.
AB  - BACKGROUND: Early indicators of treatment response in metastatic colorectal
      cancer (mCRC) could conceivably be used to optimize treatment. We explored early
      changes in circulating tumor DNA (ctDNA) levels as a marker of therapeutic
      efficacy. PATIENTS AND METHODS: This prospective study involved 53 mCRC patients
      receiving standard first-line chemotherapy. Both ctDNA and CEA were assessed in
      plasma collected before treatment, 3 days after treatment and before cycle 2.
      Computed tomography (CT) scans were carried out at baseline and 8-10 weeks and
      were centrally assessed using RECIST v1.1 criteria. Tumors were sequenced using a
      panel of 15 genes frequently mutated in mCRC to identify candidate mutations for
      ctDNA analysis. For each patient, one tumor mutation was selected to assess the
      presence and the level of ctDNA in plasma samples using a digital genomic assay
      termed Safe-SeqS. RESULTS: Candidate mutations for ctDNA analysis were identified
      in 52 (98.1%) of the tumors. These patient-specific candidate tissue mutations
      were detectable in the cell-free DNA from the plasma of 48 of these 52 patients
      (concordance 92.3%). Significant reductions in ctDNA (median 5.7-fold; P < 0.001)
      levels were observed before cycle 2, which correlated with CT responses at 8-10
      weeks (odds ratio = 5.25 with a 10-fold ctDNA reduction; P = 0.016). Major
      reductions (>=10-fold) versus lesser reductions in ctDNA precycle 2 were
      associated with a trend for increased progression-free survival (median 14.7
      versus 8.1 months; HR = 1.87; P = 0.266). CONCLUSIONS: ctDNA is detectable in a
      high proportion of treatment naive mCRC patients. Early changes in ctDNA during
      first-line chemotherapy predict the later radiologic response.

PMID- 25851627
TI  - Variation in transplacental transfer of tyrosine kinase inhibitors in the human
      perfused cotyledon model.
AB  - BACKGROUND: The use of tyrosine kinase inhibitors (TKis) during pregnancy in
      humans remains rare, and little data are available on their transplacental
      passage. Erlotinib and gefitinib are the first-line targeted therapy in case of
      stage IV nonsmall-cell lung cancer with an EGFR-activating mutation. There are no
      data available regarding the comparative use of these TKis in pregnant patients.
      We aimed to compare the transplacental transfer of gefitinib, imatinib and
      erlotinib, using the ex vivo method of human perfused cotyledon, and to determine
      the placental accumulation of TKis. MATERIALS AND METHODS: Term placentas were
      perfused after delivery with gefitinib, imatinib and erlotinib at targeted
      maternal concentrations around the steady-state plasma trough concentration (i.e.
      500, 1000 and 1500 ng/ml, respectively). Samples from fetal and maternal
      circulations were collected in order to monitor TKis concentrations. Main
      transfer parameters such as fetal transfer rate (FTR), clearance index (CI) and
      placental uptake were assessed. RESULTS: Mean FTR of gefitinib, imatinib and
      erlotinib were 16.8%, 10.6% and 31.4%, respectively. Mean CI of gefitinib,
      imatinib and erlotinib were 0.59, 0.48 and 0.93, respectively. Placental uptake
      in cotyledon was 0.030% %, 0.010% and 0.003% for gefitinib, imatinib and
      erlotinib, respectively, corresponding to a mean mass of 27.7 ug for gefitinib,
      15.7 ug for imatinib and 6.8 ug for erlotinib. CONCLUSION: The results suggest
      that TKis cross the placenta at therapeutic level. Particularly, erlotinib
      crosses the placenta at a higher rate than gefitinib or imatinib. All of them
      have a very low placental uptake. These data may suggest that gefitinib should be
      preferred to erlotinib for the treatment of pregnant woman with lung cancer
      harboring an EGFR-activating mutation, during the second and third trimesters of
      pregnancy.

PMID- 25851628
TI  - Benefit to neoadjuvant anti-human epidermal growth factor receptor 2 (HER2)
      targeted therapies in HER2-positive primary breast cancer is independent of
      phosphatase and tensin homolog deleted from chromosome 10 (PTEN) status.
AB  - BACKGROUND: Assessment of phosphatase and tensin homolog deleted from chromosome
      10 (PTEN) might be an important tool in identifying human epidermal growth factor
      receptor 2 (HER2)-positive breast cancer patients unlikely to derive benefit from
      anti-HER2 therapies. However, studies to date have failed to demonstrate its
      predictive role in any treatment setting. PATIENTS AND METHODS: Prospectively
      collected baseline core biopsies from 429 early-stage HER2-positive breast cancer
      patients treated with trastuzumab, lapatinib, or their combination in the Neo
      ALTTO study were stained using two anti-PTEN monoclonal antibodies (CST and
      DAKO). The association of PTEN status and PI3K pathway activation (defined as
      either PTEN loss and/or PIK3CA mutation) with total pathological complete
      response (tpCR) at surgery, event-free survival (EFS), and overall survival (OS)
      was evaluated. RESULTS: PTEN loss was observed in 27% and 29% of patients (all
      arms, n = 361 and n = 363) for CST and DAKO, respectively. PTEN loss was more
      frequently observed in hormone receptor (HR)-negative (33% and 36% with CST and
      DAKO, respectively) compared with HR-positive tumours (20% and 22% with CST and
      DAKO, respectively). No significant differences in tpCR rates were observed
      according to PTEN status. PI3K pathway activation was found in 47% and 48% of
      patients (all arms, n = 302 and n = 301) for CST and DAKO, respectively.
      Similarly, tpCR rates were not significantly different for those with or without
      PI3K pathway activation. Neither PTEN status nor PI3K pathway activation were
      predictive of tpCR, EFS, or OS, independently of treatment arm or HR status. High
      inter-antibody and inter-observer agreements were found (>90%). Modification of
      scoring variables significantly affected the correlation between PTEN and HR
      status but not with tpCR. CONCLUSION: These data show that PTEN status
      determination is not a useful biomarker to predict resistance to trastuzumab and
      lapatinib-based therapies. The lack of standardization of PTEN status
      determination may influence correlations between expression and relevant clinical
      end points. CLINICAL TRIALS: This trial is registered with ClinicalTrials.gov:
      NCT00553358.

PMID- 25851629
TI  - ELYPSE-7: a randomized placebo-controlled phase IIa trial with CYT107 exploring
      the restoration of CD4+ lymphocyte count in lymphopenic metastatic breast cancer
      patients.
AB  - BACKGROUND: Lymphopenia is a predictive factor for hematological toxicity,
      progression and early death in advanced cancers including metastatic breast
      cancer (MBC). CYT107 is a recombinant interleukin 7 (IL-7) (Cytheris, now
      Revimmune), well tolerated and able to expand lymphocyte pool in humans. The aims
      of this study were to determine the optimal schedule to deliver CYT107 and to
      assess its effect on clinical end points. PATIENT AND METHODS: This placebo
      controlled, double blind, phase IIa was conducted in MBC patients with <1500/ul
      lymphocytes treated with capecitabine. Using a 2-by-2 factorial design, 20
      patients were randomly allocated to four arms to receive (i) before chemotherapy:
      CYT107 or placebo; then (ii) during chemotherapy: CYT107 or placebo. The primary
      end point was CD4+ count changes before and during chemotherapy. Secondary end
      points were hematological toxicity, safety, overall response, progression-free
      survival (PFS) and overall survival (OS). Quantification and functional
      competence of circulating immune cells were also assessed. RESULTS: When
      administered before chemotherapy, CYT107 induced a significant increase of CD4+
      [+148.1% in CYT107 versus +9.9% in placebo groups, (Wilcoxon, P = 0.002)] and
      CD8+ T-cell counts, including both naive and memory subsets. When CYT107 was
      administered during chemotherapy, the magnitude of CD4+ and CD8+ increase was
      less important. No modulation of immune cell functional competence was observed.
      CYT107 was well tolerated with no related >=grade 3 adverse events except 1 fatal
      suspected unexpected serious adverse reaction (SUSAR) of uncertain relationship.
      Of the 12 cases evaluable for response, 6 of 7 patients (86%) receiving CYT107
      before chemotherapy achieved a response or stabilization, whereas two of five
      patients (40%) receiving placebo achieved the same result. No significant
      difference was observed for PFS or OS. CONCLUSION: In lymphopenic MBC, CYT107
      increases CD4+ and other T-cell subset counts without altering their function. A
      larger clinical trial to demonstrate its impact on clinical outcome is warranted.
      CLINICALTRIALSGOV IDENTIFIER: NCT01362107.

PMID- 25851631
TI  - Determining the indications for post mastectomy radiotherapy: moving from 20th
      century clinical staging to 21st century biological criteria.

PMID- 25851630
TI  - Heterogeneity of KRAS, NRAS, BRAF and PIK3CA mutations in metastatic colorectal
      cancer and potential effects on therapy in the CAPRI GOIM trial.
AB  - BACKGROUND: Evidence suggests that metastatic colorectal carcinoma (mCRC) has a
      high level of intratumor heterogeneity. We carried out a quantitative assessment
      of tumor heterogeneity for KRAS, NRAS, BRAF and PIK3CA mutations, in order to
      assess potential clinical implications. PATIENTS AND METHODS: Tumor samples (n =
      182) from the CAPRI-GOIM trial of first-line cetuximab + FOLFIRI in KRAS exon-2
      wild-type mCRC patients were assessed by next-generation sequencing that allows
      quantitative assessment of mutant genes. Mutant allelic frequency was normalized
      for the neoplastic cell content and, assuming that somatic mutations usually
      affect one allele, the Heterogeneity Score (HS) was calculated by multiplying by
      2 the frequency of mutant alleles in neoplastic cells. Therefore, HS virtually
      corresponds to the fraction of neoplastic cells carrying a specific mutation.
      RESULTS: The KRAS HS ranged between 12 and 260 with mean value of 87.1 and median
      value of 84.4, suggesting that in most CRC, the majority of neoplastic cells
      carry mutant KRAS. Similar findings were observed for NRAS (HS range 35.5-146.7;
      mean 102.8; median 117.1). In contrast, in BRAF (HS range 17.1-120; mean 54.8;
      median 54.3) and PIK3CA (HS range 14.3-120; mean 59.5; median 47.3) mutant cases,
      only a fraction of neoplastic cells seem to carry the mutant allele. The response
      rate was 70% in KRAS mutant patients with an HS <33 (low KRAS; n = 10) and 45.7%
      in KRAS HS >33 patients (high KRAS; n = 35); median progression-free survival
      were 7.97 and 8.37 months, respectively. Low-KRAS tumors had a higher frequency
      of additional mutations in PIK3CA when compared with high-KRAS (6/10 versus
      8/35). CONCLUSIONS: KRAS and NRAS mutations are usually present in the majority
      of neoplastic cells, whereas BRAF and PIK3CA mutations often affect a limited
      fraction of transformed cells. Resistance to cetuximab in low-KRAS patients might
      be driven by the complex mutational profile rather than KRAS mutation load.

PMID- 25851632
TI  - RECORD-2: phase II randomized study of everolimus and bevacizumab versus
      interferon alpha-2a and bevacizumab as first-line therapy in patients with
      metastatic renal cell carcinoma.
AB  - BACKGROUND: The open-label, phase II RECORD-2 trial compared efficacy and safety
      of first-line everolimus plus bevacizumab (EVE/BEV) with interferon plus
      bevacizumab (IFN/BEV) in patients with metastatic renal cell carcinoma. PATIENTS
      AND METHODS: Previously untreated patients were randomized 1:1 to bevacizumab 10
      mg/kg every 2 weeks with either everolimus 10 mg/day (EVE/BEV) or interferon (9
      MIU 3 times/week, if tolerated) (IFN/BEV). Tumor assessments occurred every 12
      weeks. The primary objective was the assessment of treatment effect on
      progression-free survival (PFS), based on an estimate of the chance of a
      subsequent phase III trial success (50% threshold for phase II success). RESULTS:
      Baseline characteristics were balanced between the EVE/BEV (n = 182) and IFN/BEV
      (n = 183) arms. The median PFS was 9.3 and 10.0 months in the EVE/BEV and IFN/BEV
      arms, respectively (P = 0.485). The predicted probability of phase III success
      was 5.05% (hazard ratio = 0.91; 95% confidence interval 0.69-1.19). The median
      duration of exposure was 8.5 and 8.3 months for EVE/BEV and IFN/BEV,
      respectively. The percentage of patients discontinuing because of adverse events
      (AEs) was 23.4% for EVE/BEV and 26.9% for IFN/BEV. Common grade 3/4 AEs included
      proteinuria (24.4%), stomatitis (10.6%), and anemia (10.6%) for EVE/BEV and
      fatigue (17.1%), asthenia (14.4%), and proteinuria (10.5%) for IFN/BEV. The
      median overall survival was 27.1 months in both arms. CONCLUSIONS: The efficacy
      of EVE/BEV and IFN/BEV appears similar. No new or unexpected safety findings were
      identified and, with the exception of proteinuria in about one-fourth of the
      population, EVE/BEV was generally well tolerated. CLINICAL TRIAL REGISTRY AND
      TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT00719264.

PMID- 25851633
TI  - The effect of filgrastim or pegfilgrastim on survival outcomes of patients with
      cancer receiving myelosuppressive chemotherapy.
AB  - BACKGROUND: Primary prophylaxis with granulocyte colony-stimulating factor (G
      CSF) is associated with higher chemotherapy relative dose intensity, which may
      lead to improved outcomes; however, the association between G-CSF primary
      prophylaxis and overall survival (OS) is not well characterized. This study
      assessed the effect of G-CSF primary prophylaxis on patient outcomes in
      randomized, controlled, registrational clinical trials of filgrastim and
      pegfilgrastim. PATIENTS AND METHODS: Three placebo-controlled and two non
      inferiority clinical trials of filgrastim and/or pegfilgrastim in patients
      receiving myelosuppressive chemotherapy for lung, breast, or colorectal cancer
      were included. The median OS, 6- and 12-month survival rates, and hazard ratios
      [HRs; unadjusted Cox model with 95% confidence intervals (CIs)] were estimated
      for patients receiving >=1 dose of filgrastim, pegfilgrastim, or placebo.
      Comparisons were based on a log-rank test. A fixed-effect meta-analysis assessed
      the effect of primary prophylaxis with filgrastim/pegfilgrastim on OS in the
      placebo-controlled trials. RESULTS: In patients with lung cancer receiving
      filgrastim versus placebo, the median OS was 14.1 versus 11.1 months (HR, 0.81;
      95% CI 0.48-1.35; P = 0.412); in patients who crossed over to filgrastim from
      placebo after cycle 1, the median OS was 16.9 months (HR, 0.75; 95% CI 0.43-1.28;
      P = 0.286). The median OS was inestimable in at least one treatment arm in the
      other studies because of the small number of OS events. Where estimable, 6- and
      12-month survival rates were generally greater among patients receiving
      filgrastim/pegfilgrastim versus placebo. In the meta-analysis of placebo
      controlled studies comparing G-CSF primary prophylaxis with placebo in the as
      treated analysis sets, the HR (95% CI) for OS was 0.77 (0.58-1.03). CONCLUSIONS:
      In this retrospective analysis, OS point estimates were greater among patients
      receiving filgrastim versus placebo, but the differences were not statistically
      significant. Further studies evaluating patient outcomes with G-CSF prophylaxis
      are warranted. CLINICAL TRIAL REGISTRATION: NCT00035594, NCT00094809.

PMID- 25851634
TI  - Potential of polymerase chain reaction and galactomannan for the diagnosis of
      invasive aspergillosis in patients with febrile neutropenia.
AB  - The incidence of invasive aspergillosis (IA) has increased over the last years,
      especially in immuncompromised patients with high mortality rates. Because of
      difficulties about the diagnosis; serological methods [galactomannan (GM) antigen
      test] and polymerase chain reaction (PCR) developed in recent years. MycAssay
      Aspergillus PCR performance in the diagnosis of IA was evaluated and compared
      with the GM and in-house PCR. This study was conducted with 358 serum samples
      obtained from 99 patient with febrile neutropenic episodes who were followed in
      haematology and bone marrow transplantation units. Patients were classified by
      the European Organization for the Research and Treatment of Cancer/Mycoses Study
      Group criteria, 18 of them is proven and probable IA. GM antigen test and two
      different real-time PCR; one of them is fist commercial PCR for IA; Mycassay
      Aspergillus and the other one is in-house real-time PCR performed. Sensitivity
      values were Mycassay Aspergillus PCR, in-house PCR, and GM 65.38%, 11.53% and
      23.07%, respectively. The high sensitivity obtained from Mycassay Aspergillus PCR
      and sensitivity is increased by using a combination of diagnostic methods. GM
      antigen test and real-time PCR could be beneficial for early diagnosis and
      treatment of IA. For routine usage of PCR as diagnostic assay more studies needed
      in future. 

PMID- 25851635
TI  - Acute effects of calcium citrate with or without a meal, calcium-fortified juice
      and a dairy product meal on serum calcium and phosphate: a randomised cross-over
      trial.
AB  - Ca supplements, but not dietary Ca, have been associated with increased
      cardiovascular risk. This difference could be related to differences in their
      acute effects on serum Ca. We therefore examined the effects of Ca from different
      sources on serum Ca and phosphate in a randomised, cross-over trial of ten women
      (mean age of 69 years). Fasting participants received a single dose of 500 mg of
      Ca as citrate, citrate with a meal, fortified juice or a dairy product meal, with
      at least 6 d between each intervention. Blood was sampled before and 1, 2, 4 and
      6 h after each intervention was ingested. Serum ionised and total Ca increased
      significantly from baseline over 6 h. Using calcium citrate fasting as a
      comparator, the elevations in ionised and total Ca were similar after fortified
      juice, delayed after calcium citrate with a meal and smaller after a dairy
      product meal. Serum phosphate and calcium-phosphate product increased from
      baseline after calcium citrate with a meal and after a dairy product meal, and
      they declined after calcium citrate fasting and after fortified juice. The
      elevations in serum Ca in the present study were only slightly different from
      those observed after the administration of 1000 mg of Ca in a previous study.
      These data indicate that different sources of Ca have different acute effects on
      serum Ca and support recommendations that dietary Ca might be safer than
      supplements. Whether these differences contribute to differences in
      cardiovascular risk requires further study.

PMID- 25851636
TI  - The selective dopamine D3 receptor antagonist SB-277011A attenuates drug- or food
      deprivation reactivation of expression of conditioned place preference for
      cocaine in male Sprague-Dawley rats.
AB  - We determined the effect of the selective dopamine D3 receptor antagonist SB
      277011A on reactivation of conditioned place preference (CPP) to cocaine elicited
      by priming injections of cocaine or exposure to food deprivation stress (21 h) in
      male Sprague-Dawley rats. Animals paired with the cocaine-associated chamber
      displayed a robust and consistent CPP response. This CPP was extinguished after
      repeated pairings of the conditioned stimuli (cocaine-paired chamber contextual
      cues) in the absence of the unconditioned stimulus (cocaine). Twenty-four hours
      later, the administration of 5 mg kg(-1) i.p. of cocaine (immediately before the
      test) or exposure to 21 h of food deprivation reactivated the expression of the
      cocaine-induced CPP. In contrast, administration of 1 ml kg(-1) i.p. of vehicle
      did not reactivate the CPP response. Administration of the selective dopamine D3
      receptor antagonist SB-277011A (3-24 mg kg(-1) i.p.) 30 min before cocaine
      administration on the test day produced a significant attenuation of CPP
      reactivation. Reactivation of the CPP response produced by food deprivation was
      also significantly attenuated by SB-277011A (6 or 12 mg kg(-1) i.p.) given 30 min
      before the test session. SB-277011A (12 or 24 mg kg(-1) i.p.) did not itself
      produce reactivation of the CPP response. Overall, these results suggest that the
      reactivation of the incentive value of drug-associated cues by cocaine or food
      deprivation is attenuated by selective antagonism of D3 receptors.

PMID- 25851638
TI  - Clinical assessment of drug-drug interactions of tasimelteon, a novel dual
      melatonin receptor agonist.
AB  - Tasimelteon ([1R-trans]-N-[(2-[2,3-dihydro-4-benzofuranyl] cyclopropyl) methyl]
      propanamide), a novel dual melatonin receptor agonist that demonstrates
      specificity and high affinity for melatonin receptor types 1 and 2 (MT1 and MT2
      receptors), is the first treatment approved by the US Food and Drug
      Administration for Non-24-Hour Sleep-Wake Disorder. Tasimelteon is rapidly
      absorbed, with a mean absolute bioavailability of approximately 38%, and is
      extensively metabolized primarily by oxidation at multiple sites, mainly by
      cytochrome P450 (CYP) 1A2 and CYP3A4/5, as initially demonstrated by in vitro
      studies and confirmed by the results of clinical drug-drug interactions presented
      here. The effects of strong inhibitors and moderate or strong inducers of CYP1A2
      and CYP3A4/5 on the pharmacokinetics of tasimelteon were evaluated in humans.
      Coadministration with fluvoxamine resulted in an approximately 6.5-fold increase
      in tasimelteon's area under the curve (AUC), whereas cigarette smoking decreased
      tasimelteon's exposure by approximately 40%. Coadministration with ketoconazole
      resulted in an approximately 54% increase in tasimelteon's AUC, whereas rifampin
      pretreatment resulted in a decrease in tasimelteon's exposure of approximately
      89%. 

PMID- 25851639
TI  - Living Legends: students' responses to an intergenerational life review writing
      program.
AB  - The purpose of the study was to examine the effects of participation in the
      Living Legends program upon health science students' image of older adults and
      interest in working with older people. A multisite quasi-experimental control
      group design with a connected qualitative component was used. Program sites
      included three Naturally Occurring Retirement Communities (NORCs) and one senior
      center. Health science students (n = 43) from two universities and two community
      colleges and community-dwelling seniors (n = 39) participated in the program. A
      baseline questionnaire was used to ascertain demographic characteristics and
      prior type and amount of contact with older adults. The Image of Aging Scale and
      Likert-style questions to measure interest in working with older adults were the
      primary outcome measures. Written responses to program experiences were also
      collected. Analysis of covariance was used to compare changes in Image of Aging
      subscale scores from pre- to posttest. Mean change in positive image of older
      adults subscale scores was 4.6 (SD = 4.4) for the intervention group and -0.6 (SD
      = 4.8) for the control group. The difference between groups was significant (F =
      22.0, P < .001), and the effect size was large (Cohen's d = 1.07). Nine of the 22
      students in the intervention group had a greater interest in working with seniors
      after the program. Qualitative themes that emerged included a positive and
      beneficial experience, life lessons, seeing the person beyond the visible, power
      of the written word, and shared lives. Living Legends is an effective program to
      enhance positive images of older adults in future healthcare professionals and
      may have a positive impact on some students with regard to interest in working
      with older adults.

PMID- 25851640
TI  - Prolonged flare-up of testosterone after administration of a gonadotrophin
      agonist to a sex offender: an under-recognised risk?

PMID- 25851641
TI  - Negative ion gas-phase chemistry of arenes.
AB  - Reactions of aromatic and heteroaromatic compounds involving anions are of great
      importance in organic synthesis. Some of these reactions have been studied in the
      gas phase and are occasionally mentioned in reviews devoted to gas-phase negative
      ion chemistry, but no reviews exist that collect all existing information about
      these reactions. This work is intended to fill this gap. In the first part of
      this review, methods for generating arene anions in the gas phase and studying
      their physicochemical properties and fragmentation reactions are presented. The
      main topics in this part are as follows: processes in which gas-phase arene
      anions are formed, measurements and calculations of the proton affinities of
      arene anions, proton exchange reactions, and fragmentation processes of
      substituted arene anions, especially phenide ions. The second part is devoted to
      gas-phase reactions of arene anions. The most important of these are reactions
      with electrophiles such as carbonyl compounds and alpha,beta-unsaturated carbonyl
      and related compounds (Michael acceptors). Other reactions including oxidation of
      arene anions and halogenophilic reactions are also presented. In the last part of
      the review, reactions of electrophilic arenes with nucleophiles are discussed.
      The best known of these is the aromatic nucleophilic substitution (SN Ar)
      reaction; however, other processes that lead to the substitution of a hydrogen
      atom in the aromatic ring are also very important. Aromatic substrates in these
      reactions are usually but not always nitroarenes bearing other substituents in
      the ring. The first step in these reactions is the formation of an anionic sigma
      adduct, which, depending on the substituents in the aromatic ring and the
      structure of the attacking nucleophile, is either an intermediate or a transition
      state in the reaction path. In the present review, we attempted to collect the
      results of both experimental and computational studies of the aforementioned
      reactions conducted since the very beginning of gas-phase negative ion chemistry.

PMID- 25851642
TI  - Comparison of High-Fidelity Simulation Versus Didactic Instruction as a
      Reinforcement Intervention in a Comprehensive Curriculum for Radiology Trainees
      in Learning Contrast Reaction Management: Does It Matter How We Refresh?
AB  - RATIONALE AND OBJECTIVES: Simulation-based training has been shown to be a useful
      adjunct to standard didactic lecture in teaching residents appropriate management
      of adverse contrast reactions. In addition, it has been suggested that a biannual
      refresher is needed; however, the type of refresher education has not been
      assessed. MATERIALS AND METHODS: This was a prospective study involving 31
      radiology residents across all years in a university program. All residents
      underwent standard didactic lecture followed by high-fidelity simulation-based
      training. At approximately 6 months, residents were randomized into a didactic
      versus simulation group for a refresher. At approximately 9 months, all residents
      returned to the simulation center for performance testing. Knowledge and
      confidence assessments were obtained from all participants before and after each
      phase. Performance testing was obtained at each simulation session and scored
      based on predefined critical actions. RESULTS: There was significant improvement
      in knowledge (P < .002) and confidence (P < .001) after baseline education of
      combined didactic and simulation-based training. There was no statistical
      difference between the simulation and didactic groups in knowledge or confidence
      at any phase of the study. There was no significant difference in tested
      performance between the groups in either performance testing session.
      CONCLUSIONS: This study suggests that a curriculum consisting of an annual
      didactic lecture combined with simulation-based training followed by a didactic
      refresher at 6 months is an effective and efficient (both cost-effective and time
      effective) method of educating radiology residents in the management of adverse
      contrast reactions.

PMID- 25851644
TI  - Could Blood Pressure Phobia Go Beyond the White Coat Effect?
AB  - BACKGROUND: While it is known that excessive anxiety surrounding the measuring of
      blood pressure may preclude an accurate measurement, it is not known whether it
      could also lead to phobic avoidance behavior. METHODS: Self-reported information
      was collected on 125 individuals who made postings on 5 internet-based medical
      forums. RESULTS: Qualitative thematic analysis revealed that these individuals
      reported experiencing intense fear associated with the measuring of blood
      pressure, that was excessive or irrational and which contributed to avoidance of
      medical treatment and interference with life decisions. CONCLUSIONS: Based on
      these preliminary observations, we are speculating that these symptoms could be
      considered consistent with a diagnosis of a Specific Phobia. Investigations using
      quantitative methods, representative samples, and standardized clinical
      instruments need to be conducted before definitive conclusions can be reached.

PMID- 25851643
TI  - Advanced Breast Imaging Availability by Screening Facility Characteristics.
AB  - RATIONALE AND OBJECTIVES: To determine the relationship between screening
      mammography facility characteristics and on-site availability of advanced breast
      imaging services required for supplemental screening and the diagnostic
      evaluation of abnormal screening findings. MATERIALS AND METHODS: We analyzed
      data from all active imaging facilities across six regional registries of the
      National Cancer Institute-funded Breast Cancer Surveillance Consortium offering
      screening mammography in calendar years 2011-2012 (n = 105). We used generalized
      estimating equations regression models to identify associations between facility
      characteristics (eg, academic affiliation, practice type) and availability of on
      site advanced breast imaging (eg, ultrasound [US], magnetic resonance imaging
      [MRI]) and image-guided biopsy services. RESULTS: Breast MRI was not available at
      any nonradiology or breast imaging-only facilities. A combination of breast US,
      breast MRI, and imaging-guided breast biopsy services was available at 76.0% of
      multispecialty breast centers compared to 22.2% of full diagnostic radiology
      practices (P = .0047) and 75.0% of facilities with academic affiliations compared
      to 29.0% of those without academic affiliations (P = .04). Both supplemental
      screening breast US and screening breast MRI were available at 28.0% of
      multispecialty breast centers compared to 4.7% of full diagnostic radiology
      practices (P < .01) and 25.0% of academic facilities compared to 8.5% of
      nonacademic facilities (P = .02). CONCLUSIONS: Screening facility characteristics
      are strongly associated with the availability of on-site advanced breast imaging
      and image-guided biopsy service. Therefore, the type of imaging facility a woman
      attends for screening may have important implications on her timely access to
      supplemental screening and diagnostic breast imaging services.

PMID- 25851646
TI  - The ethics of global clinical trials: In developing countries, participation in
      clinical trials is sometimes the only way to access medical treatment. What
      should be done to avoid exploitation of disadvantaged populations?

PMID- 25851645
TI  - Access to human tissues for research and product development: From EU regulation
      to alarming legal developments in Belgium.

PMID- 25851647
TI  - Excellence and the new social contract for science: In search for scientific
      excellence in a changing environment.

PMID- 25851648
TI  - Wnt directs the endosomal flux of LDL-derived cholesterol and lipid droplet
      homeostasis.
AB  - The Wnt pathway, which controls crucial steps of the development and
      differentiation programs, has been proposed to influence lipid storage and
      homeostasis. In this paper, using an unbiased strategy based on high-content
      genome-wide RNAi screens that monitored lipid distribution and amounts, we find
      that Wnt3a regulates cellular cholesterol. We show that Wnt3a stimulates the
      production of lipid droplets and that this stimulation strictly depends on
      endocytosed, LDL-derived cholesterol and on functional early and late endosomes.
      We also show that Wnt signaling itself controls cholesterol endocytosis and flux
      along the endosomal pathway, which in turn modulates cellular lipid homeostasis.
      These results underscore the importance of endosome functions for LD formation
      and reveal a previously unknown regulatory mechanism of the cellular programs
      controlling lipid storage and endosome transport under the control of Wnt
      signaling. 

PMID- 25851650
TI  - The use of omega-3 Fatty acids in nonalcoholic Fatty liver disease: the end of
      the road or a new beginning?

PMID- 25851649
TI  - Healthy rabbits are susceptible to Epstein-Barr virus infection and infected
      cells proliferate in immunosuppressed animals.
AB  - BACKGROUND: Epstein-Barr virus (EBV) is an oncogenic virus implicated in the
      pathogenesis of several human malignancies. However, due to the lack of a
      suitable animal model, a number of fundamental questions pertaining to the
      biology of EBV remain poorly understood. Here, we explore the potential of
      rabbits as a model for EBV infection and investigate the impact of
      immunosuppression on viral proliferation and gene expression. METHODS: Six
      healthy New Zealand white rabbits were inoculated intravenously with EBV and
      blood samples collected prior to infection and for 7 weeks post-infection. Three
      weeks after the last blood collection, animals were immunosuppressed with daily
      intramuscular injections of cyclosporin A at doses of 20 mg/kg for 15 days and
      blood collected twice a week from each rabbit. The animals were subsequently
      sacrificed and tissues from all major organs were collected for subsequent
      analysis. RESULTS: Following intravenous inoculation, all 6 rabbits seroconverted
      with raised IgG and IgM titres to EBV, but viral DNA in peripheral blood
      mononuclear cells (PBMCs) could only be detected intermittently. Following
      immunosuppression however, EBV DNA could be readily detected in PBMCs from all 4
      rabbits that survived the treatment. Quantitative PCR indicated an increase in
      EBV viral load in PBMCs as the duration of immunosuppression increased. At
      autopsy, splenomegaly was seen in 3/4 rabbits, but spleens from all 4 rabbit were
      EBV PCR positive. EBER-in situ hybridization and immunoshistochemistry revealed
      the presence of a large number of EBER-positive and LMP-1 positive lymphoblasts
      in the spleens of 3/4 rabbits. To a lesser extent, EBER-positive cells were also
      seen in the portal tract regions of the liver of these rabbits. Western blotting
      indicated that EBNA-1 and EBNA-2 were also expressed in the liver and spleen of
      infected animals. CONCLUSION: EBV can infect healthy rabbits and the infected
      cells proliferate when the animals are immunocompromised. The infected cells
      expressed several EBV-latent gene products which are probably driving the
      proliferation, reminiscent of what is seen in immunocompromised individuals.
      Further work is required to explore the potential of rabbits as an animal model
      for studying EBV biology and tumorigenesis.

PMID- 25851651
TI  - Visceral fat necrosis in a newborn after whole body hypothermia.

PMID- 25851652
TI  - Abdominoscrotal hydrocele presenting as abdominal pain and mass after trans
      scrotal hydrocelectomy.

PMID- 25851653
TI  - Large-Scale Examination of Factors Influencing Phosphopeptide Neutral Loss during
      Collision Induced Dissociation.
AB  - Collision-induced dissociation (CID) remains the predominant mass spectrometry
      based method for identifying phosphorylation sites in complex mixtures.
      Unfortunately, the gas-phase reactivity of phosphoester bonds results in MS/MS
      spectra dominated by phosphoric acid (H3PO4) neutral loss events, suppressing
      informative peptide backbone cleavages. To understand the major drivers of H3PO4
      neutral loss, we performed robust nonparametric statistical analysis of local and
      distal sequence effects on the magnitude and variability of neutral loss, using a
      collection of over 35,000 unique phosphopeptide MS/MS spectra. In contrast to
      peptide amide dissociation pathways, which are strongly influenced by adjacent
      amino acid side chains, we find that neutral loss of H3PO4 is affected by both
      proximal and distal sites, most notably basic residues and the peptide N-terminal
      primary amine. Previous studies have suggested that protonated basic residues
      catalyze neutral loss through direct interactions with the phosphate. In
      contrast, we find that nearby basic groups decrease neutral loss regardless of
      mobility class, an effect only seen by stratifying spectra by charge-mobility.
      The most inhibitory bases are those immediately N-terminal to the phosphate,
      presumably because of steric hindrances in catalyzing neutral loss. Further
      evidence of steric effects is shown by the presence of proline, which can
      dramatically reduce the presence of neutral loss when between the phosphate and a
      possible charge donor. In mobile proton spectra, the N-terminus is the strongest
      predictor of high neutral loss, with proximity to the N-terminus essential for
      peptides to exhibit the highest levels of neutral loss.

PMID- 25851654
TI  - Ion-to-Neutral Ratios and Thermal Proton Transfer in Matrix-Assisted Laser
      Desorption/Ionization.
AB  - The ion-to-neutral ratios of four commonly used solid matrices, alpha-cyano-4
      hydroxycinnamic acid (CHCA), 2,5-dihydroxybenzoic acid (2,5-DHB), sinapinic acid
      (SA), and ferulic acid (FA) in matrix-assisted laser desorption/ionization
      (MALDI) at 355 nm are reported. Ions are measured using a time-of-flight mass
      spectrometer combined with a time-sliced ion imaging detector. Neutrals are
      measured using a rotatable quadrupole mass spectrometer. The ion-to-neutral
      ratios of CHCA are three orders of magnitude larger than those of the other
      matrices at the same laser fluence. The ion-to-neutral ratios predicted using the
      thermal proton transfer model are similar to the experimental measurements,
      indicating that thermal proton transfer reactions play a major role in generating
      ions in ultraviolet-MALDI.

PMID- 25851656
TI  - Penile rehabilitation following prostate cancer treatment: review of current
      literature.
AB  - Radical prostatectomy (RP) and radiotherapy (RT) are highly effective in
      improving prostate cancer survival. However, both have a detrimental effect on
      erectile function (EF). Penile rehabilitation consists of understanding the
      mechanisms that cause erectile dysfunction (ED) and utilizing pharmacologic
      agents, devices or interventions to promote male sexual function. For the past
      decade, many researchers have pursued to define effective treatment modalities to
      improve ED after prostate cancer treatment. Despite the understanding of the
      mechanisms and well-established rationale for postprostate treatment penile
      rehabilitation, there is still no consensus regarding effective rehabilitation
      programs. This article reviews a contemporary series of trials that assess penile
      rehabilitation and explore treatment modalities that might play a role in the
      future. Published data and trials related to penile rehabilitation after RP and
      RT were reviewed and presented. Although recent trials have shown that most
      therapies are well-tolerated and aid in some degree on EF recovery, we currently
      do not have tangible evidence to recommend an irrefutable penile rehabilitation
      algorithm. However, advancements in research and technology will ultimately
      create and refine management options for penile rehabilitation. 

PMID- 25851655
TI  - Peroxisome proliferator-activated receptor gamma signaling in human sperm
      physiology.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) is a member of the
      PPARs, which are transcription factors of the steroid receptor superfamily.
      PPARgamma acts as an important molecule for regulating energy homeostasis,
      modulates the hypothalamic-pituitary-gonadal (HPG) axis, and is reciprocally
      regulated by HPG. In the human, PPARgamma protein is highly expressed in
      ejaculated spermatozoa, implying a possible role of PPARgamma signaling in
      regulating sperm energy dissipation. PPARgamma protein is also expressed in
      Sertoli cells and germ cells (spermatocytes). Its activation can be induced
      during capacitation and the acrosome reaction. This mini-review will focus on how
      PPARgamma signaling may affect fertility and sperm quality and the potential
      reversibility of these adverse effects. 

PMID- 25851657
TI  - Androgen-deprivation therapy alone versus combined with radiation therapy or
      chemotherapy for nonlocalized prostate cancer: a systematic review and meta
      analysis.
AB  - In this paper, we reviewed the long-term survival outcomes, safety, and quality
      of-life of androgen-deprivation therapy (ADT) alone versus combined with
      radiation therapy (RT) or chemotherapy for locally advanced and metastatic
      prostate cancer (PCa). A literature search was performed using OvidSP. Randomized
      controlled trials (RCTs) that met the following criteria were included: including
      locally advanced or metastatic PCa, comparing ADT alone versus combined with any
      treatment method and reporting quantitative data of disease control or survival
      outcomes. Finally, eight RCTs met the inclusion criteria. Among these, three
      compared ADT versus ADT plus RT (n = 2344) and one compared ADT versus ADT plus
      docetaxel-estramustine (n = 413) in locally advanced PCa; two compared ADT versus
      ADT plus docetaxel (n = 1175) and two compared ADT versus ADT plus estramustine
      (n = 114) in metastatic PCa. For locally advanced PCa, the addition of RT to long
      term ADT can improve the outcomes of survival and tumor control with fully
      acceptable adverse effects. Specially, the pooled odds ratio (OR) of overall
      survival (OS) was 1.43 (95% confidence interval 1.20-1.71) when compared ADT plus
      RT with ADT alone (P < 0.0001). For metastatic hormonally sensitive PCa, the
      concurrent use of docetaxel plus ADT was effective and safe (pooled OR of OS:
      1.29 [1.01-1.65]: P = 0.04). In all, long-term ADT plus RT and long-term ADT plus
      docetaxel should be considered as proper treatment option in locally advanced and
      metastatic hormonally sensitive PCa, respectively. The major limitation for the
      paper was that only eight RCTs were available. 

PMID- 25851658
TI  - Is serum sex hormone-binding globulin a dominant risk factor for metabolic
      syndrome?
AB  - This multi-center, cross-sectional study investigated the association between
      serum testosterone (T) levels, serum sex hormone-binding globulin (SHBG) levels,
      and the risk of metabolic syndrome (MS) in 3332 adult Chinese men. The prevalence
      of MS was 34.7%, and men with MS had lower serum levels of total T (TT) and SHBG
      than those without MS (P < 0.001). There was no significant difference in serum
      free T (FT) levels between subjects with and without MS (P = 0.627). In logistic
      regression analysis, the association between MS and serum SHBG levels persisted
      after adjusting for age, body mass index (BMI), smoking and drinking status, and
      serum TT (odds ratio [OR] 0.962, 95% confidence interval [95% CI] 0.954-0.969, P<
      0.01). However, the association between serum TT level and the risk of MS was
      weak after adjusting for age, BMI, SHBG level, and smoking and drinking status
      (OR 0.981, 95% CI 0.960-1.007). Our study reveals that both serum TT and SHBG
      levels, but not serum FT, are inversely associated with the prevalence of MS and
      that serum SHBG is an independent and dominant risk factor for MS. 

PMID- 25851659
TI  - The hazardous effects of tobacco smoking on male fertility.
AB  - The substantial harmful effects of tobacco smoking on fertility and reproduction
      have become apparent but are not generally appreciated. Tobacco smoke contains
      more than 4000 kinds of constituents, including nicotine, tar, carbonic monoxide,
      polycyclic aromatic hydrocarbons, and heavy metals. Because of the complexity of
      tobacco smoke components, the toxicological mechanism is notably complicated.
      Most studies have reported reduced semen quality, reproductive hormone system
      dysfunction and impaired spermatogenesis, sperm maturation, and spermatozoa
      function in smokers compared with nonsmokers. Underlying these effects, elevated
      oxidative stress, DNA damage, and cell apoptosis may play important roles
      collaboratively in the overall effect of tobacco smoking on male fertility. In
      this review, we strive to focus on both the phenotype of and the molecular
      mechanism underlying these harmful effects, although current studies regarding
      the mechanism remain insufficient. 

PMID- 25851660
TI  - RNA binding proteins in spermatogenesis: an in depth focus on the Musashi family.
AB  - Controlled gene regulation during gamete development is vital for maintaining
      reproductive potential. During the complex process of mammalian spermatogenesis,
      male germ cells experience extended periods of the inactive transcription despite
      heavy translational requirements for continued growth and differentiation. Hence,
      spermatogenesis is highly reliant on mechanisms of posttranscriptional regulation
      of gene expression, facilitated by RNA binding proteins (RBPs), which remain
      abundantly expressed throughout this process. One such group of proteins is the
      Musashi family, previously identified as critical regulators of testis germ cell
      development and meiosis in Drosophila, and also shown to be vital to sperm
      development and reproductive potential in the mouse. This review describes the
      role and function of RBPs within the scope of male germ cell development,
      focusing on our recent knowledge of the Musashi proteins in spermatogenesis. The
      functional mechanisms utilized by RBPs within the cell are outlined in depth, and
      the significance of sub-cellular localization and stage-specific expression in
      relation to the mode and impact of posttranscriptional regulation is also
      highlighted. We emphasize the historical role of the Musashi family of RBPs in
      stem cell function and cell fate determination, as originally characterized in
      Drosophila and Xenopus, and conclude with our current understanding of the
      differential roles and functions of the mammalian Musashi proteins, Musashi-1 and
      Musashi-2, with a primary focus on our findings in spermatogenesis. This review
      highlights both the essential contribution of RBPs to posttranscriptional
      regulation and the importance of the Musashi family as master regulators of male
      gamete development. 

PMID- 25851661
TI  - The epididymis re-visited: a personal view.
AB  - The sperm maturation and storage functions of the epididymis are important
      determinants of ejaculate quality, and perhaps provide an avenue to male
      contraception. In the last 50 years, the creation of epididymal fertility
      profiles in laboratory animals was followed by recognition of new sperm
      maturation-related parameters (organization of the acrosome, of the sperm
      plasmalemma, and -S-S- -based structural change) which made it possible to
      confirm that a similar pattern of sperm maturation obtains in man. The novel
      sperm storage function of the cauda epididymidis in therian mammals is regulated
      by androgen, usually in conjunction with the low temperature of the scrotum. The
      temperature-dependence of the scrotal cauda is reflected in the secretory and ion
      transport functions of the epithelium, in its duct dimensions and so in sperm
      storage capacity. Moreover, a variety of indirect evidence suggests that an
      elevated temperature of the cauda created by clothing may be compromising its
      function in man. The pattern of change in the sperm plasmalemma involving
      sterols, and also glycosylphosphatidylinositol-linked macromolecules as
      spermatozoa enter the cauda region, may underlie the need for their capacitation
      subsequently in the female tract. Further, in a variety of taxa the anatomy of
      the scrotum, together with the U-shaped configuration of the epididymis/vas
      deferens, suggests that the cauda's storage function may also underlie the
      evolution of the scrotum. Finally, despite the still relative paucity of
      comparative evidence, we can consider now why the epididymis has come to be
      organized as it is.

PMID- 25851662
TI  - Mechanisms of fertilization elucidated by gene-manipulated animals.
AB  - Capacitation and the acrosome reaction are key phenomena in mammalian
      fertilization. These phenomena were found more than 60 years ago. However,
      fundamental questions regarding the nature of capacitation and the timing of the
      acrosome reaction remain unsolved. Factors were postulated over time, but as
      their roles were not verified by gene-disruption experiments, widely accepted
      notions concerning the mechanism of fertilization are facing modifications.
      Today, although in vitro fertilization systems remain our central research tool,
      the importance of in vivo observations must be revisited. Here, primarily
      focusing on our own research, I summarize how in vivo observations using gene
      manipulated animals have elucidated new concepts in the mechanisms of
      fertilization. 

PMID- 25851664
TI  - Short-term impacts of sodium/glucose co-transporter 2 inhibitors in Japanese
      clinical practice: considerations for their appropriate use to avoid serious
      adverse events.
AB  - Sodium/glucose co-transporter 2 inhibitors (SGLT2i) represent a novel class of
      glucose-lowering agents that lower plasma glucose levels through pharmacological
      inhibition of glucose reuptake from the kidney, independent of insulin secretion
      and action. Clinical trials of SGLT2i demonstrated therapeutic benefits on
      glycemic control and bodyweight in individuals with type 2 diabetes, with few
      cases of serious adverse events (SAEs). However, a considerable number of SAEs
      were reported in patients receiving SGLT2i clinically in Japan during the first 3
      months of their use. These included urogenital infections, hypoglycemia and
      dehydration. Unexpectedly, serious skin and subcutaneous disorders, mainly
      reported as generalized rash or skin eruption, were prominent in patients
      receiving SGLT2i, but with unknown mechanisms. There is also concern for
      potential SAEs associated with chronic SGLT2i administration, especially in the
      non-obese type 2 diabetes characterized by reduced insulin secretion often seen
      in East Asia. Chronic SAEs may include severe hypoglycemia due to depletion of
      hepatic glycogen storage, acceleration of diabetes-associated sarcopenia and
      ketosis/ketoacidosis. The current information on acute SAEs confirms the
      importance of caution in the appropriate use of SGLT2i. Furthermore, careful long
      term observation of patients receiving SGLT2i is essential to avoid SAEs and for
      better clinical use of this drug class. 

PMID- 25851665
TI  - Vascular causes of sudden death in infancy, childhood, and adolescence.
AB  - Vascular causes of sudden death in infancy, childhood, and adolescence range from
      primary disorders of the vasculature involving structural compromise, as in
      anomalous coronary arteries, to vascular problems that may arise as secondary
      phenomena, such as the infectious arteritides. The etiology of the underlying
      condition may be understood, as in fatal pulmonary thromboembolism, or it may be
      shrouded in mystery, as in idiopathic arterial calcinosis. The absence of a
      clinical history indicating an underlying vascular problem in a number of
      disorders that may cause sudden childhood death underlines the importance of a
      meticulous autopsy examination in such cases. 

PMID- 25851663
TI  - Tamoxifen stimulates calcitonin-producing thyroid C-cells and prevents trabecular
      bone loss in a rat model of androgen deficiency.
AB  - Thyroid C-cells produce calcitonin (CT), a hypocalcemic hormone, that acts as an
      inhibitor of bone resorption. In this study, we investigated the effects of
      tamoxifen (TAM) as a selective estrogen receptor modulator on thyroid C-cells,
      trabecular bone and biochemical markers of bone metabolism in an animal model of
      androgen deficiency, represented by middle-aged orchidectomized (Orx) rats.
      Fifteen-month-old male Wistar rats were divided into: Orx and sham-operated (SO)
      groups. Rats from one Orx group were injected subcutaneously with TAM citrate
      (Orx + TAM; 0.3 mg kg(-1) b.w.), while the rats from SO and a second Orx group
      received vehicle alone, once a day for 3 weeks. The peroxidase-antiperoxidase
      method was applied for localization of CT in C-cells. Thyroid C-cells were
      morphometrically and ultrastructurally analyzed. An ImageJ image-processing
      program was used to measure bone histomorphometric parameters. Blood serum
      samples were analyzed for CT, osteocalcin (OC), calcium (Ca2+ ) and phosphorus
      (P). Urinary Ca2+ concentrations were measured. TAM treatment significantly
      increased thyroid C-cell volume (Vc ) and serum CT when compared with vehicle
      treated Orx rats. Analysis of trabecular microarchitecture of the tibia showed
      that administration of TAM significantly increased cancellous bone area,
      trabecular thickness and trabecular number, whereas trabecular separation was
      significantly decreased compared with vehicle-treated Orx rats. Serum OC and
      urinary Ca2+ concentrations were significantly lower in comparison with the
      control Orx group. These results indicate that in our rat model of androgen
      deficiency, TAM stimulated calcitonin-producing thyroid C-cells and increased
      trabecular bone mass.

PMID- 25851666
TI  - Microscopic findings associated with blood pressure indices in postmortem human
      aorta samples from young people (ages 15-34).
AB  - Standardized postmortem samples of thoracic and abdominal aortas from traumatic
      death victims (aged 15-34 inclusive) were selected according to renal indices of
      estimated blood pressure. Half of the males had renal small-artery evidence of
      elevated blood pressure, and half did not. The group consisted of an
      approximately equal number of black and white males. All of the individuals were
      nonsmokers and had similar age, cholesterol, and HDL distribution. Lipid
      deposition in the thoracic and abdominal aorta sections was determined
      quantitatively by means of computer micromorphometry in sections stained with Oil
      Red O. Results showed that there is a marked increase in extracellular lipid
      deposition in the intima for those arteries studied with elevated renal indices
      of hypertension. In addition, there is significantly more extracellular lipid in
      the abdominal aortas in black males than in white males. Also notable was the
      finding that the thoracic aorta samples exhibited significantly thicker intimas
      and larger intimal areas in the high blood pressure index groups than in the low
      blood pressure index groups. These results suggest that the development of
      atherosclerotic lesions may be due to an increased deposition of extracellular
      lipid in the matrix of the arterial intima. 

PMID- 25851667
TI  - Analysis of atherosclerotic plaques obtained by coronary atherectomy: Foam cells
      correlated positively with subsequent restenosis.
AB  - Restenosis following coronary intervention is a complex process the mechanisms of
      which remains mostly unknown. Tissue obtained by atherectomy is an important
      means to study restenosis. Previous studies on atherectomy-retrieved tissue have
      not identified histologic features that correlate with restenosis. We performed
      an histopathologic evaluation on atherosclerotic plaque tissue obtained by
      atherectomy from 58 patients, all of whom had a 6-month angiographic follow-up.
      We identified macrophages and lymphocytes and localized tumor necrosis factor
      alpha expression in the tissue by immunohistochemistry. Histopathology was
      correlated with late angiographic outcomes. Of 10 histologic features evaluated
      in the plaque tissue, only the presence of foam cells, identified in paraffin
      sections, correlated positively with restenosis (p = 0.04). Immunohistochemistry
      showed that macrophages (p = .07), tumor necrosis factor-alpha (p = .07), and
      lymphocytes (p = .14) were more prominent, but not significantly so, in lesions
      from patients with foam cells and restenosis than in lesions from patients
      without foam cells or restenosis. Thus the presence of foam cells in primary
      lesions obtained by atherectomy as identified in paraffin-embedded tissue appears
      to be a marker for restenosis. 

PMID- 25851669
TI  - The center for cardiovascular diseases and comparative medicine opens at the Pig
      Research Institute, Taiwan, Republic of China.

PMID- 25851668
TI  - Cardiomegaly in a young infant.

PMID- 25851670
TI  - Cardiovascular pathology in the land of doges.

PMID- 25851671
TI  - Minimally Invasive Plate Osteosynthesis in Open Pediatric Tibial Fractures.
AB  - OBJECTIVES: The aim of this study is to investigate the effectiveness and
      reliability of limited-contact locking plates in minimally invasive percutaneous
      osteosynthesis (MIPO) of the lateral tibia. DESIGN: A retrospective study.
      PATIENTS AND METHODS: The retrospective study included 14 patients who were
      operatively treated with an MIPO technique due to open tibial fractures between
      2006 and 2012. The patients were 11 males and 3 females with a mean age of 13.2
      (range, 9 to 16) years. The patients were followed up for a mean period of 2.4
      (range, 1 to 5) years. The mechanism of the injuries included a motor vehicle
      accident (n=11), a shotgun injury (n=2), and a fall from height (n=1). According
      to the Gustilo-Anderson classification, 10 patients had type I (72%), 2 had type
      II (14%), and 2 had type III (14%) open fractures. RESULTS: The mean time to
      radiologic union was 18 (range, 11 to 32) weeks. No infection was detected that
      would require implant removal. No complications such as early epiphyseal closure,
      angulation, or limb-length inequality were observed. CONCLUSIONS: Limited-contact
      locking plates in MIPO of the lateral tibia is an effective alternative method in
      the treatment of open pediatric tibial fractures. LEVEL OF EVIDENCE: Level IV
      therapeutic.

PMID- 25851672
TI  - Validity and Comprehensibility of Physical Activity Scales for Children With
      Sport Injuries.
AB  - BACKGROUND: Adult physical activity scales are used with children but may not be
      valid in this population. This study assesses the appropriateness and
      comprehensibility of currently used physical activity scales in children,
      identifies sources of response errors, and suggests scale modifications. METHODS:
      Cognitive interviews were conducted with 30 children who had a lower extremity
      injury, purposefully sampled based on age and sex. Interviews were conducted to
      identify children's comprehension of 6 physical activity questionnaires: Tegner
      activity scale, Cincinnati Knee Rating System, KOOS-Child, Marx activity scale,
      HSS Pedi-FABS, and KOS sports activity scale. RESULTS: The Tegner scale uses
      complex activity level descriptions (eg, competitive vs. recreational sports,
      types of sports and inclusion of work-related physical activity). Activity
      frequency, description of movement, and sport type in the Cincinnati Knee Rating
      System led to response mapping issues in many children. Most children felt the
      KOOS-Child pictures depicting activities were helpful, but not all found the 7
      day timeframe relevant. Whereas, most children found the Marx scale and HSS Pedi
      FABS items clear, concise, and easy to answer. Children reported difficulties
      differentiating between endurance and duration items used in the HSS Pedi-FABS.
      The consistent response format of the KOS sports activity scale was considered a
      positive attribute although children had trouble comprehending terms such as
      grating and grinding. CONCLUSIONS: Children found some scales too difficult to
      answer, whereas others required modifications, particularly in general
      instruction, language, question format, and mapping (matching an answer to
      potential options) to adapt to the specific needs of children. LEVEL OF EVIDENCE:
      Level II.

PMID- 25851673
TI  - Arthroscopic Lateral Retinacular Release in Adolescents With Medial
      Patellofemoral Ligament-centered Knee Pain.
AB  - BACKGROUND: The medial patellofemoral ligament (MPFL) has been implicated as a
      common pain generator in adolescents with anterior knee pain. The purpose of this
      study is to report the clinical outcomes of arthroscopic lateral retinacular
      release (ALRR) for refractory MPFL-centered pain and to identify risk factors for
      poor outcomes and surgical failures. METHODS: A single-surgeon database was
      queried to identify all patients undergoing ALRR. Inclusion criteria included
      minimum 12-month follow-up and ALRR performed for MPFL pain rather than for
      generalized anterior knee pain or patellar instability. All patients had
      persistent MPFL-centered pain despite participating in a nonsurgical protocol
      before surgery. Primary outcomes included International Knee Documentation
      Committee (IKDC) subjective score and need for further surgery, typically tibial
      tubercle osteotomy (TTO). RESULTS: Eighty-eight knees in 71 patients [66 female,
      5 male; average age, 15.7 y (range, 8.4 to 20.2 y)] were included. Average follow
      up was 59 months (range, 12 to 138 mo). Average preoperative IKDC score was 41.9
      (range, 18.4 to 67.8), whereas average postoperative IKDC score was 77.8 (range,
      11.5 to 98.9; P<0.01). Postoperative IKDC scores were worse in patients with a
      preoperative sulcus angle of <134 degrees than those with sulcus angle of >=134
      degrees (69.9+/-22.1 vs. 82.0+/-12.5, P=0.04). Lower preoperative IKDC score
      correlated negatively with improvement of IKDC score postoperatively (r=-0.40,
      P<0.05). Seventeen knees (19.3%) subsequently underwent TTO for persistent
      symptoms. Patients who ultimately required TTO were younger than patients who did
      not (14.8+/-1.5 vs. 15.9+/-2.1; P=0.04) and had lower mean preoperative
      Blackburne-Peel ratio (0.95+/-0.25 vs. 1.11+/-0.24; P=0.02). CONCLUSIONS: This
      study demonstrates that patients with refractory MPFL-centered knee pain had
      significant improvements in clinical outcomes after undergoing ALRR at mean 5
      years' follow-up. Poor outcomes and surgical failures were associated with lower
      preoperative IKDC score, younger age, lower preoperative Blackburne-Peel ratio,
      and sulcus angle of <134 degrees. Outcomes were not recorded prospectively, but
      mean IKDC scores <60 months postoperatively were similar to those collected >=60
      months after surgery (80.4 vs. 78.3, P=0.15). LEVEL OF EVIDENCE: Level IV.

PMID- 25851674
TI  - Early Career Experience of Pediatric Orthopaedic Fellows: What to Expect and Need
      for Their Services.
AB  - INTRODUCTION: A dramatic increase in the number of pediatric orthopaedic fellows
      being trained has led to concerns that there may be an oversupply of pediatric
      orthopaedists. The purpose of this study was to determine whether this perception
      is accurate and whether the practice expectations of recent pediatric fellowship
      graduates are being met by surveying recent pediatric fellowship graduates about
      their early practice experiences. METHODS: A 36-question survey approved by the
      Pediatric Orthopaedic Society of North America (POSNA) leadership was
      electronically distributed to 120 recent graduates of pediatric orthopaedic
      fellowships; 81 responses were ultimately obtained (67.5% response rate).
      RESULTS: Almost all (91%) of the respondents were very or extremely satisfied
      with their fellowship experience. Half of the respondents had at least 1 job
      offer before they entered their fellowships. After completion of fellowships, 35%
      received 1 job offer and 62.5% received >=2 job offers; only 2.5% did not receive
      a job offer. Most reported a practice consisting almost entirely of pediatric
      orthopaedics, and 93.5% thought this was in line with their expectations; 87%
      indicated satisfaction with their current volume of pediatric orthopaedics, and
      85% with the complexity of their pediatric orthopaedic cases. Despite the high
      employment percentages and satisfaction with practice profiles, nearly a third
      (28%) of respondents replied that too many pediatric orthopaedists are being
      trained. CONCLUSIONS: Positive messages from this survey include the satisfaction
      of graduates with their fellowship training, the high percentage of graduates who
      readily found employment, and the satisfaction of graduates with their current
      practice environments; this indicates that the pediatric orthopaedic job
      environment is not completely saturated and there are continued opportunities for
      graduating pediatric fellows despite the increased number of fellows being
      trained. Although not determined by this study, it may be that the stable demand
      for pediatric orthopaedic services is being driven by the expansion of the scope
      of practice as well as subspecialization within the practice of pediatric
      orthopaedics.

PMID- 25851675
TI  - A Preliminary Study to Assess Whether Spinal Fusion for Scoliosis Improves Carer
      assessed Quality of Life for Children With GMFCS Level IV or V Cerebral Palsy.
AB  - BACKGROUND: Scoliosis affects 50% of children with Gross Motor Function
      Classification System (GMFCS) level IV or V cerebral palsy (CP). In children with
      complex neurodisability following intervention, the WHO considers quality of life
      (QoL) should be assessed to aid decision-making and assess the effects. This
      study assesses whether scoliosis surgery improves carer-assessed QoL for children
      with severe CP. METHODS: Retrospective review of 33 children (16 male:17 female)
      with GMFCS level IV/V CP and significant scoliosis. Fifteen underwent
      observational treatment during childhood, and 18 underwent surgery. Questionnaire
      and radiographic data were recorded over a 2-year period. The carer-completed
      Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD)
      questionnaire was used to assess QoL. RESULTS: In the observational group, Cobb
      angle and pelvic obliquity increased from 46 (40 to 60) and 8 degrees (0 to 28)
      to 62 (42 to 94) and 12 degrees (1 to 35). Mean CPCHILD score decreased from 50
      (30 to 69) to 48 (27 to 69) (P<0.05). In the operative group, Cobb angle and
      pelvic obliquity decreased from 78 (52 to 125) and 14 degrees (1 to 35) to 44 (16
      to 76) and 9 degrees (1 to 24). Mean CPCHILD score increased from 45 (20 to 60)
      to 58 (37 to 76) (P<0.05). Change in pain, and not presence of associated
      impairments, was the most significant factor affecting QoL changes for children
      in both groups. There was no difference in mobility, GMFCS level, feeding, or
      communication in either group before and after treatment. CONCLUSIONS:
      Nonoperative treatment for children with GMFCS level IV/V CP and a significant
      scoliosis was associated with a small decrease in carer-assessed QoL over 2
      years. Spinal fusion was associated with an increase in QoL. Change in pain was
      the most significant factor affecting QoL changes, and is therefore an important
      factor to consider when deciding upon surgery. LEVEL OF EVIDENCE: Level III
      therapeutic retrospective study.

PMID- 25851676
TI  - Sonographic Assessment of Hip Swaddling Techniques in Infants With and Without
      DDH.
AB  - BACKGROUND: The purpose of this single-examination pilot study was to confirm the
      ability to perform hip sonography while swaddled and to ascertain whether the
      various swaddling techniques influenced hip position and dynamics. METHODS:
      Dynamic sonography was used to evaluate 30 infants in both swaddled and
      unswaddled positions who were being seen in clinic for suspected or documented
      developmental dysplasia of the hip. A "treatment group" of 16 infants (32 hips)
      treated in a Pavlik harness and a "nontreatment group" of 14 untreated infants
      (28 hips) were studied.Criteria for comparing sonographic results between
      swaddled and unswaddled hip positions included femoral head position,
      instability, and range-of-motion restriction. RESULTS: Tight swaddling with a
      blanket was applied in 11 "nontreatment group" cases (20 hips; in 2 cases, only 1
      hip studied) and produced limited flexion and abduction. One unstable left hip
      dislocated when tightly swaddled. Safe swaddling technique in 12 cases (24 hips)
      showed no limitation of flexion and abduction of the legs and no change in
      stability by sonography. Commercial swaddling products appeared to mildly
      restrict leg motion in 14 hips, but there was no change in hip position in the
      "nontreatment group." However, the commercial swaddling products changed the hip
      position in 3 Pavlik harness cases. CONCLUSIONS: Swaddling techniques that allow
      a free range of leg motion may not affect hip stability in normal infants or
      those being treated with Pavlik harness. Swaddling with restricted leg motion
      increases potential for hip instability. Tight swaddling dislocated 1 unstable
      hip, and commercial swaddling products judged to apply only mild restriction of
      leg motion negatively impacted 3 cases being treated for developmental dysplasia
      of the hip with Pavlik harness. On the basis of this pilot study, we advise
      caution when swaddling infants, especially with techniques that restrict leg
      motion. Further study of the long-term effects of swaddling is warranted. LEVEL
      OF EVIDENCE: Level II.

PMID- 25851677
TI  - Risk Factors of Refracture and Morbidity During Removal of Titanium Pediatric
      Proximal Femoral Locking Plates in Children With Cerebral Palsy.
AB  - BACKGROUND: Pediatric proximal femoral locking plates (PFLPs) are widely used
      when performing proximal femoral osteotomy in children with cerebral palsy (CP).
      The purpose of this study is to report the difficulties and risk factors of
      titanium PFLPs removal in CP. METHODS: PFLP removal was performed in 58 hips of
      33 patients (17 males, 16 females). The mean age at the time of surgery (plate
      removal) was 10.9 (range, 5.7 to 19.2) years. The patients were divided into 2
      groups as group 1 and 2, if any difficulty was observed during surgery or not.
      RESULTS: Difficulty was not detected in 42 (72.4%) hips (group 1). Difficulties
      were encountered in 16 (27.6%) hips (group 2). A total of 364 screws were used
      (259 in group 1, 105 in group 2). The mean plate screw density ratios were 0.88
      in group 1 and 0.94 in group 2. The difference between group 1 and 2 was
      statistically significant. The mean duration between the insertion and removal of
      the PFLP was 14.9 months (11.9 mo in group 1, 22.7 mo in group 2). The difference
      between group 1 and 2 was statistically significant. The screw heads were cut and
      the shafts were left in the bone in 4 hips (4 screws); 3 of these 4 screws were
      calcar screws. Therefore, calcar screw application can be accepted as a handicap
      for screw removal. CONCLUSIONS: As a conclusion, this study suggested that
      difficulty in titanium PFLP removal in CP is common and PFLP removal is not a
      harmless procedure. A longer time from internal fixation to removal, increased
      plate screw density ratio, and calcar screw application are risk factors for
      difficulties in titanium PFLP removal in CP. LEVEL OF EVIDENCE: Level III.

PMID- 25851678
TI  - First 50 Pediatric and Adolescent Elbow Arthroscopies: Analysis of Indications
      and Complications.
AB  - BACKGROUND: Elbow arthroscopy is a challenging, yet extremely productive
      procedure in orthopaedic sports medicine. The severely confined anatomy of the
      pediatric and adolescent elbow is particularly prone for perioperative
      complications. This study focuses on the indications and complications of the
      first 50 elbow arthroscopies in skeletally immature patients done in a
      specialized pediatric orthopaedic department. PURPOSE: To review analysis of
      indications and complications in pediatric and adolescent elbow arthroscopy. We
      hypothesized that the complication rate in these patients is similar to adults.
      METHODS: Data on 50 consecutive elbow arthroscopies were prospectively gathered
      in a dedicated database and retrospectively analyzed for indications and
      perioperative complications. All procedures were performed by a surgeon trained
      in orthopaedic sports medicine. RESULTS: A total of 26 boys and 24 girls with a
      mean age of 13.6+/-3.3 years at the time of surgery and a minimum follow-up of 1
      year were included.Fifty-eight percent were treated for osteochondritis
      dissecans, 24% for arthrofibrosis, 14% for a congenital disorder, and 4% for a
      posttraumatic problem other than arthrofibrosis. The complication rate was 8%,
      including 3 cases of transient neuropraxia and 1 superficial wound infection.
      There were no major complications such as septic arthritis, vascular injury, or
      permanent nerve damage. All complications resolved fully with conservative
      treatment, no revision were required. DISCUSSION: Although osteochondritis
      dissecans is still the leading reason for such surgery, fractures and
      posttraumatic conditions are becoming more important. With a rate of 5% to 8% of
      minor, fully resolving complications such an increase is not a reason for
      concerns. LEVEL OF EVIDENCE: Level IV-case series.

PMID- 25851679
TI  - Are Orthopaedic Residents Competent at Performing Basic Nonoperative Procedures
      in an Unsupervised Setting? A "Pop Quiz" of Casting, Knee Arthrocentesis, and
      Pressure Checks for Compartment Syndrome.
AB  - BACKGROUND: Many patient care procedures are routinely performed by orthopaedic
      residents while not directly supervised by attending physicians. However,
      resident competence to perform these procedures is often presumed and not
      confirmed by objective measures. The purpose of this study was to formally
      evaluate 3 basic pediatric orthopaedic procedures commonly performed without
      attending supervision. METHODS: All orthopaedic residents (n=20) were asked to
      complete 3 procedures (placement and removal of a short arm cast, aspiration of a
      knee joint, and compartment pressure checks of a leg) under direct attending
      supervision. Attending faculty developed a checklist for each procedure, listing
      the appropriate steps required and criteria with which to assess the final
      results. Scores were calculated, including means and SDs. Change in score by
      postgraduate year level was determined by simple linear regression. RESULTS: The
      mean score for short arm cast application and removal was 6.2 of a total possible
      score of 8, with an average 1.1 increase in score per year of training (P<0.001).
      Uneven cast padding and lack of full thumb motion were the most common reasons
      for losing points. Knee joint aspiration had an average score of 6.2 of 7, with
      an average increase in score of 0.3 per year of training (P=0.046). Lack of
      equipment preparation and not donning gloves in a sterile manner were the most
      common reasons for losing points. Measure of leg compartment pressures had an
      average score of 9.7 of 12, with an average increase in score of 0.5 per increase
      in year of training (P=0.087). Injecting an inappropriate amount of fluid and not
      recording measurements were the most common reasons for losing points.
      CONCLUSIONS: The ability of a resident to appropriately perform certain
      procedures without direct supervision improves with advancing level of training.
      The most junior residents might not appropriately be placing short arm casts,
      aspirating knee joints, or checking compartment pressures of the leg. LEVEL OF
      EVIDENCE: Level II-Diagnostic.

PMID- 25851680
TI  - Stuffed Animals in the Operating Room: A Reservoir of Bacteria With a Simple
      Solution.
AB  - BACKGROUND: Despite hand washing and other protocols surgical-site infections
      (SSIs) have not been eliminated. This implies that either current measures are
      not effective or there are alternative sources of bacterial exposure to the
      surgical wound. In this study we tested the hypothesis that stuffed animals or
      other items allowed to accompany pediatric patients to the operating room as a
      way to ease anxiety may represent a reservoir of bacteria. METHODS: Stuffed
      animals brought into the operating room and stuffed animals that were washed and
      dried in a conventional washer/dryer and placed in clean sealable plastic bags
      were swabbed and bacterial colonies were quantified. Results were reported as no
      growth, light growth, moderate growth, and heavy growth. RESULTS: All stuffed
      animals showed bacterial growth. A total of 79% of stuffed animals were
      effectively "sterilized" by a single wash and dry cycle in a conventional home
      washer/dryer. Sterilized stuffed animals remained sterile after being packed in a
      sealed bag for 24 hours. CONCLUSIONS: These results indicate that items of
      comfort, such as stuffed animals, brought into the operating room with a
      benevolent purpose may represent a reservoir of bacteria that could lead to
      unwanted SSI. Washing an item of comfort 1 day before surgery effectively
      sterilizes that item of comfort. Future studies will be needed to determine a
      correlation between "culture positive" stuffed animals and SSI or if providing a
      child with a "sterile" stuffed animal reduces SSI.

PMID- 25851681
TI  - Outcomes of Orthopaedic Surgery With and Without an External Femoral Derotational
      Osteotomy in Children With Cerebral Palsy.
AB  - BACKGROUND: Ambulatory children with cerebral palsy (CP) often present with
      multiple deviations in all planes including increased internal hip rotation
      during gait. Excessive femoral anteversion is a common cause of deviation managed
      surgically with an external femoral derotational osteotomy (FDO). The purpose of
      this study was to evaluate the gait and functional outcomes of a group of
      subjects with CP who underwent surgical intervention that included an FDO
      compared with a match group with indications of internal hip rotation that did
      not receive an FDO. METHODS: For this retrospective study, subjects were
      identified from the Motion Analysis Laboratory database that had orthopaedic
      surgery including an FDO (FDO group). A control group was established from a
      chart review identifying subjects that had indications for an FDO, but did not
      have this surgery (No-FDO group). All subjects had preoperative and postoperative
      gait studies. Subjects categorized as Gross Motor Function Classification System
      (GMFCS) levels I and II in both FDO and No-FDO groups were combined for analysis.
      Subjects rated as GMFCS level III were analyzed separately. Preoperative to
      postoperative kinematic and kinetic variables, Gait Deviation Index, net oxygen
      cost, and PODCI scores were analyzed with paired t tests. RESULTS: Typical
      sagittal plane kinematic variables improved significantly by equivalent
      magnitudes for both FDO and No-FDO groups (GMFCS I/II and III). Transverse plane
      improvements were only seen for the FDO group (GMFCS I/II and III). The Gait
      Deviation Index, an overall index of kinematics, improved by a significantly
      greater amount for the FDO group across GMFCS levels I/II and III. Net oxygen
      cost improved for both FDO and No-FDO for GMFCS I/II. PODCI scores improved for
      FDO and No-FDO in GMFCS I/II, but only the FDO group for GMFCS III. CONCLUSIONS:
      For children with CP, inclusion of an FDO in the surgical intervention, when
      indicated, resulted in improved outcomes. Overall gait kinematic improvements
      were significantly greater when an FDO was included in the surgical management.
      LEVEL OF EVIDENCE: Level III-retrospective comparative study.

PMID- 25851682
TI  - Fractures at Diagnosis in Infants and Children With Osteogenesis Imperfecta.

PMID- 25851683
TI  - Characterization of Hip Morphology in Children With Mucopolysaccharidosis Types I
      and II.
AB  - BACKGROUND: The purpose of this study is to describe the natural history of hip
      morphology in patients with mucopolysaccharidoses (MPS) I and MPS II.
      METHODOLOGY: This is a retrospective radiographic analysis of 88 hips in 44
      children with MPS I and II. Radiographs were examined to determine hip migration,
      femoral head sphericity, and acetabular dysplasia at different ages throughout
      childhood. In individual hips, change in morphology and rate of change were
      analyzed. RESULTS: There was a high rate of hip migration and femoral head
      dysplasia in both MPS I and MPS II. Progressive migration was seen in three
      quarters of hips and progressive femoral head deformity in over half of hips.
      Acetabular dysplasia was variable, ranging from normal to severely dysplastic,
      but did not change with time. Overall, hips were more dysplastic in MPS I than
      MPS II. CONCLUSIONS: Hip morphology is variable in MPS I and MPS II ranging from
      almost normal to severely dysplastic. Some hips do not deteriorate with time and
      thus surgical intervention may not be necessary in all cases. Deterioration is
      slow allowing time to plan a holistic approach to treatment. LEVEL OF EVIDENCE:
      Level IV-case series.

PMID- 25851684
TI  - Utilizing the "Stable-to-be Vertebra" Saves Motion Segments in Growing Rods
      Treatment for Early-Onset Scoliosis.
AB  - BACKGROUND: There is no consensus on the selection of distal instrumentation
      levels in growing rod surgery. Many surgeons utilize the stable zone of
      Harrington, but there is not overwhelming evidence to support this preference.
      The aim of this study was to determine the value of bending/traction radiographs
      in selection of distal instrumentation levels of a growing rod construct in
      children with idiopathic or idiopathic-like early-onset scoliosis (EOS). METHODS:
      Twenty-three consecutive patients with idiopathic or idiopathic-like EOS who
      underwent growing rod surgery at 2 separate institutions between 2006 and 2011
      were included. Lengthening procedures were performed periodically at 6-month
      intervals. Analyses were performed retrospectively for age at index surgery,
      follow-up period, and radiographic measurements. Lower instrumented levels,
      neutral vertebra, stable vertebrae (SV), and stable-to-be vertebrae (StbV) were
      identified on the preoperative radiographs. Coronal Cobb angles, tilt of lower
      instrumented vertebra (LIV) and LIV+1, and disk wedging under the LIV and LIV+1
      were measured on the early postoperative and latest follow-up radiographs.
      RESULTS: Average age at index surgery was 83.6 months. Mean follow-up period was
      68.1 months. Initial analysis showed that the relationship of LIV to the StbV was
      a better predictive of LIV+1 tilt than the SV at the final follow-up. Therefore,
      the patients were grouped according to the relationship of the LIV to the StbV.
      LIV was the StbV in 9 patients, proximal to the StbV in 8 patients, and distal to
      the StbV in 6 patients. At the latest follow-up, tilt of LIV+1 exceeded 10
      degrees in 7 of the 8 patients where LIV was proximal to the StbV, whereas only
      in 1 of 9 patients where LIV was StbV, and in none of the 6 patients where LIV
      was distal to the StbV. The data indicate that selection of the StbV as the LIV
      could spare an average of 1.8 vertebral segments when compared with the SV, as
      StbV is never distal but almost always proximal to the SV. CONCLUSIONS: Choosing
      the StbV as the LIV saves motion segments and prevents distal adding on, while
      providing satisfactory deformity correction in idiopathic and idiopathic-like
      EOS. LEVEL OF EVIDENCE: Level III-retrospective comparative study.

PMID- 25851685
TI  - Do Surgical Times and Efficiency Differ Between Inpatient and Ambulatory Surgery
      Centers That are Both Hospital Owned?
AB  - PURPOSE: The aim of this study was to examine the differences in primary anterior
      cruciate ligament reconstruction (ACLR) surgical time and operation room (OR)
      work efficiency between inpatient and ambulatory facilities within the same
      institution. METHODS: Patients studied included those who underwent primary ACLR
      at either the inpatient hospital or the ambulatory facility by a single
      orthopaedic surgeon on elective surgery days. Time variables were calculated for
      ACLR to compare the 2 facilities. The OR work efficiency was calculated as the
      percentage of work that was completed before mid-day that was determined by the
      midpoint of the surgical day at each facility. RESULTS: Two hundred twenty-seven
      ACLR surgeries were performed on 187 elective surgery days, 153 surgeries at the
      inpatient facility and 74 at the outpatient facility. The mean age at the time of
      surgery was 14.9+/-2.2 years. The ACLR surgeries at the ambulatory facility were
      of shorter duration than those at the inpatient facility (P<0.0001). One OR was
      most commonly utilized and 2 to 3 surgeries were performed on most surgery days
      at both facilities. Seven nurses served as alternating circulators at the
      ambulatory facility compared with 41 nurses serving in the same capacity at the
      inpatient facility. The median turnover time was longer at the inpatient facility
      compared with the ambulatory facility. OR work efficiency (work done before mid
      day) was 72.5% at the ambulatory facility and 49.5% at the inpatient facility,
      P<0.0001. If 2 ACLR surgeries were performed consecutively, the surgery day
      lasted for 6 hours at the hospital-owned ambulatory surgery center compared with
      9 hours at the inpatient hospital. CONCLUSIONS: Despite the common variables of
      the same surgeon performing the same surgery at facilities owned by the same
      institution primarily working in a single OR, differences exist in OR procedure
      time and work efficiency. LEVEL OF EVIDENCE: Level III.

PMID- 25851686
TI  - Disproportionate Participation of Males and Females in Academic Pediatric
      Orthopaedics: An Analysis of Abstract Authorship at POSNA 2009-2013.
AB  - BACKGROUND: Despite increasing numbers of female orthopaedic surgeons, we
      hypothesized that women were not actively participating at national and
      international meetings in numbers proportional to their membership. METHODS: A
      retrospective review of the 2009-2013 POSNA Annual Meeting Final Programs was
      performed. The following information was recorded for all members: name, sex,
      membership level, years of membership, and if the individual was an author on at
      least 1 abstract. To compare proportion of abstract authorship between sexes
      across years, while controlling for years of membership, general estimating
      equations with a binomial model and logit link were used. The study population
      was limited to candidate and active POSNA members only, as this group represents
      the most active practicing pediatric orthopaedic surgeons. RESULTS: Over the 5
      year period studied, females comprised 16.6% (204/1227) of the total POSNA
      membership and 20.9% (184/880) of members at candidate and active status. The
      percentage of females with candidate or active member status in POSNA who had at
      least 1 abstract presentation during the 5 years was 37% and this was
      significantly lower (P=0.003) than the percentage of men (49%) who presented at
      least 1 abstract. Analysis across the 5 years showed a consistent difference
      between the sexes with no trend of convergence in abstract rates (P=0.65).
      Controlling for years membership, female members still presented abstracts at
      lower rates than their male colleagues (P=0.002). CONCLUSIONS: Female members of
      POSNA, in the most active part of their careers, participated at significantly
      lower rates than their male peers as accepted abstract authors for the 2009-2013
      POSNA meetings than would be expected for their proportional size of total
      membership.

PMID- 25851687
TI  - Compartment Pressures in Children With Normal and Fractured Forearms: A
      Preliminary Report.
AB  - INTRODUCTION: Acute compartment syndrome (ACS) can lead to irreversible damage if
      fasciotomy is not performed in a timely manner. Needle manometry is a tool to
      confirm suspected ACS. The threshold for compartment pressures that can be
      tolerated has been debated. The aim of this study is to assess the normal
      compartment pressures in noninjured forearms of children. Further, we sought to
      quantify the maximum tolerable compartment pressures in fractured forearms of
      children, thus establishing a baseline and providing guidance in evidence-based
      decision making to evaluate children with suspected ACS. METHODS: This
      prospective study included children up to the age of 16 years with forearm
      fractures that needed reduction with or without osteosynthesis. Between June 2009
      and March 2013, 41 children were included. Mean age was 9.25 years (range, 4 to
      15.4 y). We used needle manometry to measure the pressures in the superficial and
      deep volar as well as in the dorsal compartments (DCs) on both the forearms. The
      mean pressures between compartments in healthy versus injured arms were analyzed
      using a 1-sided, paired t test. RESULTS: On the injured side, the mean
      compartment pressure was 19.12 mm Hg (range, 3 to 49 mm Hg) in the deep volar
      compartment, 15.56 mm Hg (range, 5 to 37 mmHg) in the DC, and 14.8 mm Hg (range,
      2 to 35 mm Hg) in the superficial volar compartment. On the noninjured side, the
      mean compartment pressure was 12.9 mm Hg (range, 6 to 31 mm Hg) in the DC, 10.22
      mm Hg (range, 3 to 22 mm Hg) in the deep volar compartment, and 9.66 mm Hg
      (range, 3 to 21 mm Hg) in the superficial volar compartment. We measured an
      absolute compartment pressure of >30 mm Hg in 15 patients on the fractured side.
      Three of them had an absolute compartment pressure of >45 mm Hg. Only 1 had ACS.
      This patient underwent fasciotomy and was excluded for further analysis. On
      follow-up (mean, 24.84 mo), no patient was found to have any sequelae of ACS.
      DISCUSSION: This is the first study to report normal compartment pressure
      measurements in noninjured forearms and in fractured forearms without clinical
      suspicion of ACS in children.The mean compartment pressure measured in the deep
      volar compartment (DVC) in healthy children was 10.22 mm Hg (range, 3 to 22 mm
      Hg) and therefore slightly higher than in adults. Some children with fractures
      tolerated absolute compartment pressures >30 mm Hg without clinical signs of ACS.
      Fasciotomy in children under close observation could eventually be delayed
      despite surpassing the accepted pressure limits for adults. LEVEL OF EVIDENCE:
      Level I-prognostic.

PMID- 25851688
TI  - Reliability and Effectiveness of Smartphone Technology for the Diagnosis and
      Treatment Planning of Pediatric Elbow Trauma.
AB  - BACKGROUND: Mobile imaging, such as viewing radiographs as text messages, is
      increasingly prevalent in clinical settings. The purpose of this study was to
      determine whether remote diagnosis of pediatric elbow fractures using smartphone
      technology is reliable. In addition, this study aimed to determine whether the
      assessment regarding the decision for operative treatment is affected by
      evaluation of images on a mobile device as opposed to standard picture archiving
      and communication system (PACS). METHODS: Standard anteroposterior and lateral
      radiographs of 50 pediatric elbow trauma cases were evaluated by 2 fellowship
      trained pediatric orthopaedic surgeons and 2 senior orthopaedic residents. Raters
      were asked to classify the case as any of 6 diagnoses: supracondylar humerus,
      lateral condyle, medial epicondyle, radial neck fracture, positive posterior fat
      pad sign, or normal pediatric elbow. Raters were asked to choose operative or
      conservative treatment. After 1 week, photographs of the same images were taken
      from a standardized distance from a computer monitor with an iPhone 5 camera and
      transmitted by multimedia messaging to each rater. The same questions were again
      posed to raters. Interobserver and intraobserver reliabilities were calculated by
      Cohen kappa-statistics with bootstrapped 95% confidence intervals. RESULTS:
      Intraobserver reliability of classification of injuries on PACS compared with
      smartphone images was excellent, with an overall kappa of 0.91. Treatment
      decision also demonstrated excellent intraobserver reliability (PACS vs.
      smartphones) with a kappa of 0.86 for all raters. CONCLUSIONS: Diagnosis of
      pediatric elbow injuries can be made equally reliably based on either PACS or
      transmitted multimedia messaging images taken with an iPhone camera from a
      computer screen and viewed on a smartphone. Treatment decisions can also be made
      reliably based on either image modality. CLINICAL RELEVANCE: Using smartphones to
      transmit and display radiographs, which is common in current clinical practice,
      is effective and reliable for diagnosis and treatment planning of pediatric elbow
      injuries.

PMID- 25851689
TI  - Doctor-to-doctor communication of prognosis in metastatic cancer: a review of
      letters from medical oncologists to referring doctors.
AB  - BACKGROUND: Shared understanding of prognosis is vital for optimal,
      multidisciplinary, clinical decision making. AIMS: This study aims to determine
      the frequency and nature of prognostic information in medical oncologists'
      letters to referring doctors for patients with metastatic cancer. METHODS: We
      reviewed all consultation letters (to June 2014) for new patients with metastatic
      cancer presenting to medical oncologists at Concord and Macarthur Cancer Centres
      between June 2012 and June 2013. We recorded the presence and nature of
      prognostic information in the letters, patients' characteristics and survival.
      Characteristics associated with inclusion of prognostic information were
      explored. RESULTS: We analysed 1344 letters pertaining to 272 patients with a
      median survival of 13 months. The median number of letters per patient was 4
      (interquartile range 1-7), with 50% written by trainees. The terms 'metastatic'
      or 'stage IV cancer' were included in letters for 253 patients (93%), treatment
      was described as 'palliative' for 174 patients (64%) and the word 'incurable' was
      included for 93 (34%). Only 31 patients (11%) had a quantitative estimate of
      prognosis in any correspondence: median or average survival in 14, general time
      frame in 12 and, best case, typical and worst case scenarios in 5. Inclusion of
      quantitative prognostic information was not associated with patient age, cancer
      type, treatment plan, trainee authoring letter or shorter survival. CONCLUSION:
      Inclusion of quantitative prognostic information in written correspondence from
      medical oncologists regarding patients with metastatic cancer was infrequent.
      Encouraging oncologists to include quantitative prognostic information in their
      letters could improve communication between oncologists, referring doctors and
      patients.

PMID- 25851690
TI  - Two Years of Cinacalcet Hydrochloride Treatment Decreased Parathyroid Gland
      Volume and Serum Parathyroid Hormone Level in Hemodialysis Patients With Advanced
      Secondary Hyperparathyroidism.
AB  - The long-term effect of cinacalcet hydrochloride treatment on parathyroid gland
      (PTG) volume has been scarcely investigated in patients with moderate to advanced
      secondary hyperparathyroidism (SHPT). The present study was a prospective
      observational study to determine the effect of cinacalcet treatment on PTG volume
      and serum biochemical parameters in 60 patients with renal SHPT, already treated
      with intravenous vitamin D receptor activator (VDRA). Measurement of biochemical
      parameters and PTG volumes were performed periodically, which were analyzed by
      stratification into tertiles across the baseline parathyroid hormone (PTH) level
      or PTG volume. We also determined the factors that can estimate the changes in
      PTG volume and the achievement of the target PTH range by multivariable analyses.
      Two years of cinacalcet treatment significantly decreased the serum levels of
      PTH, calcium, and phosphate, followed by the improvement of achieving the target
      ranges for these parameters recommended by the Japanese Society for Dialysis
      Therapy. Cinacalcet decreased the maximal and total PTG volume by about 30%, and
      also decreased the serum PTH level independent of the baseline serum PTH level
      and PTG volume. Ten out of 60 patients showed 30% increase in maximal PTG after 2
      years. Multivariable analysis showed that patients with nodular PTG at baseline
      and patients with higher serum calcium and PTH levels at 1 year were likely to
      exceed the target range of PTH at two years. In conclusion, cinacalcet treatment
      with intravenous VDRA therapy decreased both PTG volume and serum intact PTH
      level, irrespective of the pretreatment PTG status and past treatment history. 

PMID- 25851691
TI  - Effect of lopinavir/ritonavir on the pharmacokinetics of selexipag an oral
      prostacyclin receptor agonist and its active metabolite in healthy subjects.
AB  - AIMS: This study investigated the effect of a fixed dose combination of
      lopinavir/ritonavir on the pharmacokinetics (PK) of selexipag and its active
      metabolite ACT-333679. METHODS: This was an open label, randomized, single
      centre, two way, crossover study. Twenty healthy male subjects were treated with
      a single dose of 400 ug selexipag alone and in combination with multiple doses of
      lopinavir/ritonavir (400/100 mg) twice daily. RESULTS: The results showed that
      lopinavir/ritonavir approximately doubled the exposure to selexipag. The area
      under the plasma concentration-time curve from time zero to infinity
      (AUC(0,infinity) and the maximum plasma concentration (Cmax) of selexipag were
      2.2- and 2.1-fold higher, respectively, than under selexipag alone, with a 90%
      confidence interval (CI) of the geometric mean ratio (GMR) of 1.9, 2.7 and 1.7,
      2.6, respectively. For ACT-333679, the clinically more relevant component of
      selexipag, systemic exposure was increased by 8% (GMR of AUC(0,infinity) 1.1, 90%
      CI 0.9, 1.3), when lopinavir/ritonavir was co-administered with selexipag. The
      most frequently reported adverse event (AE) was headache. A single dose of
      selexipag, administered either alone or together with multiple doses of
      lopinavir/ritonavir, was safe and well tolerated. CONCLUSIONS:
      Lopinavir/ritonavir does not affect the PK parameters of selexipag and ACT-333679
      to a clinically relevant extent. Therefore, adaptation of the selexipag dose is
      not required when co-administered with inhibitors of the organic anion
      transporting polypeptide (OATP) 1B1/ 1B3, P-glycoprotein (P-gp) and/or CYP3A4.

PMID- 25851692
TI  - Transcriptional refractoriness is dependent on core promoter architecture.
AB  - Genes are often transcribed in random bursts followed by long periods of
      inactivity. Here we employ the light-activatable white collar complex (WCC) of
      Neurospora to study the transcriptional bursting with a population approach.
      Activation of WCC by a light pulse triggers a synchronized wave of transcription
      from the frequency promoter followed by an extended period (~1 h) during which
      the promoter is refractory towards restimulation. When challenged by a second
      light pulse, the newly activated WCC binds to refractory promoters and has the
      potential to recruit RNA polymerase II (Pol II). However, accumulation of Pol II
      and phosphorylation of its C-terminal domain repeats at serine 5 are impaired.
      Our results suggest that refractory promoters carry a physical memory of their
      recent transcription history. Genome-wide analysis of light-induced transcription
      suggests that refractoriness is rather widespread and a property of promoter
      architecture.

PMID- 25851694
TI  - Reviewing post-publication peer review.
AB  - Post-publication peer review (PPPR) is transforming how the life sciences
      community evaluates published manuscripts and data. Unsurprisingly, however, PPPR
      is experiencing growing pains, and some elements of the process distinct from
      standard pre-publication review remain controversial. I discuss the rapid
      evolution of PPPR, its impact, and the challenges associated with it. 

PMID- 25851695
TI  - Detection of manipulations on printed images to address crime scene analysis: A
      case study.
AB  - Photographic documents both in digital and in printed format plays a fundamental
      role in crime scene analysis. Photos are crucial to reconstruct what happened and
      also to freeze the fact scenario with all the different present objects and
      evidences. Consequently, it is immediate to comprehend the paramount importance
      of the assessment of the authenticity of such images, to avoid that a possible
      malicious counterfeiting leads to a wrong evaluation of the circumstance. In this
      paper, a case study in which some printed photos, brought as documental evidences
      of a familiar murder, had been fraudulently modified to bias the final judgement
      is presented. In particular, the usage of CADET image forensic tool, to verify
      printed photos integrity, is introduced and discussed. 

PMID- 25851693
TI  - Formation and activation of thermogenic fat.
AB  - Thermogenic fat cells that convert chemical energy into heat are present in both
      mice and humans. Recent years have witnessed great advances in our understanding
      of the regulation of these adipocytes and an increased appreciation of the
      potential these cells have to counteract obesity. We summarize recent efforts to
      understand the formation of these fat cells and critically review genetic models
      and other experimental tools currently available to further investigate the
      development and activation of both classical brown and inducible beige fat cells.
      We also discuss recent discoveries about the epigenetic regulation of these
      adipocytes, and finally present emerging evidence revealing the metabolic impacts
      of thermogenic fat in humans. 

PMID- 25851696
TI  - REPORT-HF: the unique blend of global heart failure registry and longitudinal
      cohort study.

PMID- 25851697
TI  - The relationship between serum 25(OH)D and bone density and microarchitecture as
      measured by HR-pQCT.
AB  - The relation between serum 25-hydroxy vitamin D [25(OH)D] and bone quality is not
      well understood, particularly for high levels. We measured bone microarchitecture
      in three groups of people stratified by their serum 25(OH)D. There was a weak
      association of serum 25(OH)D and microarchitecture for this cross-sectional
      population, suggesting possible benefits to bone quality. INTRODUCTION: Vitamin D
      plays an important role in bone and mineral metabolism, but the relation between
      serum 25(OH)D and bone quality is not well understood. Here, we present a cross
      sectional study that investigated a convenience group of participants from an
      ongoing health initiative in Alberta, Canada, who have been receiving daily
      vitamin D supplementation. METHODS: A total of 105 participants were organized
      into three groups based on their serum 25(OH)D levels: low (<75 nmol/L), medium
      (75-175 nmol/L), and high (>175 nmol/L). They were also assessed with 25(OH)D as
      a continuous variable. Average daily supplementation was 7670 +/- 438 IU, and the
      change in 25(OH)D ranged from 22 to 33 % during the period of receiving
      supplements. We used high-resolution peripheral quantitative computed tomography
      measurements at the radius and tibia to assess bone microarchitecture. RESULTS:
      Microarchitectural parameters were not strongly associated with serum 25(OH)D. In
      the tibia, there were fewer trabeculae (TbN; p = 0.015) and a non-significant
      trend toward thicker trabeculae (p = 0.067) of the high group. Body mass index
      (BMI) was negatively associated with serum 25(OH)D levels (p < 0.001) and PTH
      levels (p < 0.001). There was no clinically significant relationship detected
      between high serum 25(OH)D and high serum calcium. CONCLUSION: These data suggest
      a weak relationship between serum 25(OH)D and bone microarchitecture in this
      population of mostly vitamin-D-sufficient participants, and there were no
      indications of negative effects related to the high supplementation levels. These
      data provided a basis to design and implement our 3-year dose-dependent
      randomized controlled trial investigating the effects of vitamin D
      supplementation on bone health outcomes.

PMID- 25851698
TI  - A tuber calcanei avulsion fracture developed on the basis of idiopathic
      osteoporosis in a young male: a case report.
AB  - Calcaneus fractures constitute 1.2 % of all fractures. Tuber calcanei avulsion
      fractures constitute 1.3-2.7 % of calcaneus fractures. Osteoporosis,
      osteomalacia, and diabetes mellitus have been reported to increase the risk of
      development of these fractures. It has been reported that tuber calcanei avulsion
      fractures in elderly females might develop due to osteoporosis. As far as we
      know, no tuber calcanei avulsion fracture developing on the basis of osteoporosis
      without presence of a trauma has been reported in young males in the literature.
      In the current case report, a 41-year-old male patient who was admitted with
      complaints of pain in the left heel and diagnosed with calcaneal avulsion
      fracture that developed on the basis of idiopathic osteoporosis and who was
      treated with conservative methods was presented. 

PMID- 25851699
TI  - Prior ankle fractures in postmenopausal women are associated with low areal bone
      mineral density and bone microstructure alterations.
AB  - In a cross-sectional analysis in postmenopausal women, prior ankle fractures were
      associated with lower areal bone mineral density (BMD) and trabecular bone
      alterations compared to no fracture history. Compared to women with forearm
      fractures, microstructure alterations were of lower magnitude. These data suggest
      that ankle fractures are another manifestation of bone fragility. INTRODUCTION:
      Whether ankle fractures represent fragility fractures associated with low areal
      bone mineral density (aBMD) and volumetric bone mineral density (vBMD) and/or
      bone microstructure alterations remains unclear, in contrast to the well
      recognised association between forearm fractures and osteoporosis. The objective
      of this study was to investigate aBMD, vBMD and bone microstructure in
      postmenopausal women with prior ankle fracture in adulthood, compared with women
      without prior fracture or with women with prior forearm fractures, considered as
      typically of osteoporotic origin. METHODS: In a cross-sectional analysis in the
      Geneva Retirees Cohort study, 63 women with ankle fracture and 59 with forearm
      fracture were compared to 433 women without fracture (mean age, 65 +/- 1 years).
      aBMD was measured by dual-energy X-ray absorptiometry; distal radius and tibia
      vBMD and bone microstructure were measured by high-resolution peripheral
      quantitative computed tomography. RESULTS: Compared with women without fracture,
      those with ankle fractures had lower aBMD, radius vBMD (-7.9%), trabecular
      density (-10.7%), number (-7.3%) and thickness (-4.6%) and higher trabecular
      spacing (+14.5%) (P < 0.05 for all). Tibia trabecular variables were also
      altered. For 1 standard deviation decrease in total hip aBMD or radius trabecular
      density, odds ratios for ankle fractures were 2.2 and 1.6, respectively, vs 2.2
      and 2.7 for forearm fracture, respectively (P <= 0.001 for all). Compared to
      women with forearm fractures, those with ankle fractures had similar spine and
      hip aBMD, but microstructure alterations of lower magnitude. CONCLUSION: Women
      with ankle fractures have lower aBMD and vBMD and trabecular bone alterations,
      suggesting that ankle fractures are another manifestation of bone fragility.

PMID- 25851701
TI  - Ventricular Fibrillation due to Automated Atrial Threshold Testing in a Patient
      with an Implantable Cardioverter Defibrillator.

PMID- 25851700
TI  - Small molecule ice recrystallization inhibitors enable freezing of human red
      blood cells with reduced glycerol concentrations.
AB  - In North America, red blood cells (RBCs) are cryopreserved in a clinical setting
      using high glycerol concentrations (40% w/v) with slow cooling rates (~1 degrees
      C/min) prior to storage at -80 degrees C, while European protocols use reduced
      glycerol concentrations with rapid freezing rates. After thawing and prior to
      transfusion, glycerol must be removed to avoid intravascular hemolysis. This is a
      time consuming process requiring specialized equipment. Small molecule ice
      recrystallization inhibitors (IRIs) such as beta-PMP-Glc and beta-pBrPh-Glc have
      the ability to prevent ice recrystallization, a process that contributes to
      cellular injury and decreased cell viability after cryopreservation. Herein, we
      report that addition of 110 mM beta-PMP-Glc or 30 mM beta-pBrPh-Glc to a 15%
      glycerol solution increases post-thaw RBC integrity by 30-50% using slow cooling
      rates and emphasize the potential of small molecule IRIs for the preservation of
      cells. 

PMID- 25851702
TI  - Cost-Effectiveness of Long-Term Every Three-Year Versus Annual Postoperative
      Surveillance for Low-Risk Papillary Thyroid Cancer.
AB  - BACKGROUND: Patients with low-risk papillary thyroid cancer (PTC) who demonstrate
      an excellent response to initial therapy have a 2% recurrence rate and 100%
      disease-specific survival within 10 years. Thus, annual surveillance may be
      excessive. We hypothesized that less frequent postoperative surveillance in these
      patients is cost effective. METHODS: A Markov discrete time state transition
      model was created to compare postoperative surveillance tapered to 3-year
      intervals after 5 years of annual surveillance versus conventional annual
      surveillance in low-risk PTC patients with negative neck ultrasound and
      stimulated thyroglobulin less than 2 ng/mL 1 year postoperatively. Outcome
      probabilities, utilities, and costs were determined via literature review, the
      Medicare Physician Fee Schedule, and Healthcare Cost and Utilization Project
      data. Sensitivity analyses were performed to assess areas of uncertainty.
      RESULTS: The cost of annual surveillance was $5,239 per patient and yielded 22.49
      quality-adjusted life-years (QALYs). The 3-year strategy cost $2,601 less, but
      also yielded 0.01 less QALYs. Thus, the incremental cost per QALY of annual
      surveillance was $260,100. Probabilistic sensitivity analysis demonstrated that
      less frequent surveillance was more cost effective in 99.98% of 10,000 simulated
      patients. One-way sensitivity analysis revealed that annual surveillance would be
      cost effective if the total cost of neck ultrasound could be reduced to $23 or
      less. CONCLUSION: Extending postoperative surveillance to 3-year intervals after
      5 years of annual surveillance in patients with low-risk PTC with excellent
      response to therapy is more cost effective than annual surveillance.

PMID- 25851703
TI  - Role of Apoptosis in the Development of Uterine Leiomyoma: Analysis of Expression
      Patterns of Bcl-2 and Bax in Human Leiomyoma Tissue With Clinical Correlations.
AB  - To describe gene expression patterns of the apoptotic regulatory genes Bcl and
      Bax in human uterine leiomyoma tissue. To investigate the relationship between
      alterations of gene expression patterns and several relevant clinical parameters.
      We obtained samples from 101 cases undergoing surgery for uterine leiomyoma for
      gene expression analysis of the Bcl-2 and Bax genes. Gene expression was
      quantified using RT-PCR technique. In the leiomyoma group, the Bcl-2 gene was
      significantly overexpressed compared with the control group although there was no
      such difference in the gene expression of Bax. Gene activity of Bcl-2 positively
      correlated with the tumor number in individual uterine leiomyoma cases. Although
      there was no significant correlation between the length of the cumulative
      lactation period before the development of uterine leiomyoma and Bcl-2 gene
      expression in the leiomyoma tissue, we observed a trend for a shorter cumulative
      lactation period to be associated with overexpression of the Bcl-2 gene.
      Overexpression of the antiapoptotic Bcl-2 gene appeared to be a factor in the
      development of uterine leiomyoma, whereas gene activity of the proapoptotic Bax
      gene did not seem to play a role in the process. 

PMID- 25851704
TI  - Endometrial Carcinomas With Clear Cells: A Study of a Heterogeneous Group of
      Tumors Including Interobserver Variability, Mutation Analysis, and
      Immunohistochemistry With HNF-1beta.
AB  - Endometrial clear cell carcinoma (CC) is an uncommon tumor and often carries a
      poor prognosis. It has histologic features that overlap with other endometrial
      carcinomas and is frequently misclassified. Accurate classification is crucial,
      however, to improve treatment options. The objectives of this study were (1) to
      assess diagnostic interobserver variability among 5 gynecologic pathologists for
      tumors originally diagnosed as CC or with a component of CC (n=44); (2) to
      determine the utility of immunohistochemical markers estrogen receptor and HNF
      1beta; and (3) to detect mutations in select genes. Clinical data and morphologic
      features were also recorded. Agreement among reviewers was only moderate: only
      46% of the original CC remained classified as such. After reclassification,
      estrogen receptor was positive in 8% of CC, 67% of endometrioid carcinomas (EC),
      and 47% of serous carcinomas (SC). Sensitivities of HNF-1beta in CC, SC, and EC
      were 62%, 27%, and 17%, respectively, whereas specificity for CC versus EC or SC
      was 78%. Mutations in PIK3CA, PIK3R1, PTEN, KRAS, and NRAS were detected in 41%
      of 37 cases that had adequate material for study. At least 1 mutation was
      identified in 33% of CC, 67% of EC, and 33% of SC. This group of patients had
      poor outcomes: 72% of the patients with follow-up information had died of
      disease. In summary, this study suggests that the current pool of CC is a
      heterogeneous group of tumors from the morphologic, immunophenotypic, and
      molecular point of views and that only a percentage of them represent true CC. 

PMID- 25851705
TI  - Giant Cell Tumor of the Uterus: A Report of 3 Cases With a Spectrum of
      Morphologic Features.
AB  - Giant cell tumors, a well-recognized neoplasm of bone, can rarely be found in the
      uterus. Such tumors are characterized by a dual population of mononuclear and
      osteoclast-like giant cells that lack epithelial and specific mesenchymal
      differentiation. In this study, the clinicopathologic features of 3 giant cell
      tumors of the uterus were reviewed. Immunohistochemistry for CD68, CD163, h
      caldesmon, desmin, SMA, AE1/AE3, CD10, ER, PR, cyclin D1, CD1a, CD34, CD30, S100,
      myogenin/myoglobin, and Ki-67 was performed in all tumors, along with
      ultrastructural analysis in one. The patients were 47, 57, and 59 yr and the
      tumors measured 2.5, 7.5, and 16.0 cm. One neoplasm was confined to the
      endometrium, whereas the other 2 were myometrial. All 3 tumors showed a nodular
      growth comprised of mononuclear and osteoclast-like giant cells. The endometrial
      confined tumor consisted of histologically benign mononuclear cells, whereas the
      others exhibited marked atypia. Mitotic activity was up to 5/10 HPF in the benign
      tumor and up to 22/10 HPF in the malignant. No cytologic atypia or mitoses were
      observed in the giant cells. CD68 and CD10 were strongly and diffusely expressed
      in both components of 3 and 2 neoplasms, respectively. Cyclin D1 was focal in the
      mononuclear cells and focal to diffuse in the giant cells. CD163 was diffuse in
      the mononuclear cells, but absent to focal in the giant cells. Ultrastructural
      analysis lacked diagnostic features of epithelial or specific mesenchymal
      differentiation. Both malignant tumors demonstrated an aggressive behavior. In
      summary, although rare, giant cell tumor of the uterus should be included in the
      differential diagnosis of benign or malignant tumors containing osteoclast-like
      giant cells. 

PMID- 25851706
TI  - Sclerosing Stromal Tumors With Prominent Luteinization During Pregnancy: A Report
      of 8 Cases Emphasizing Diagnostic Problems.
AB  - Ovarian tumors encountered during pregnancy can pose a diagnostic challenge due
      to an abundance of luteinized cells and other changes. We report 8 sclerosing
      stromal tumors with massive luteinization discovered in pregnant patients. The
      tumors ranged from 3.1 to 21 cm (mean=8.8 cm) in size and were typically solid
      and yellow; the neoplasm was bilateral in 1 case. On microscopic examination, the
      lutein cells, a feature of sclerosing stromal tumor, had more copious
      eosinophilic cytoplasm and were more numerous than is usually seen in nonpregnant
      patients and to varying degrees obscured the typical pseudolobular pattern. This
      resulted in particular diagnostic difficulty in 3 cases, especially when
      associated with other changes including irregular shapes of tumor cell nests,
      edema, and/or myxoid change. However, classic features of these tumors: ectatic
      vessels and admixed luteinized and nonluteinized cells were still focally
      evident, allowing for accurate classification. The tumors were cytologically
      bland and with 1 exception had rare mitoses. As sclerosing stromal tumors have
      been invariably benign, it is important that they not be confused with other
      tumors, such as steroid cell tumor, which can occasionally be malignant. 

PMID- 25851707
TI  - Placental Molar Disease: What are the Benefits and Barriers to the Adoption of a
      Comprehensive Diagnostic Service?
AB  - The molecular cytogenetic analysis of specimens (genotyping) suspicious for
      hydatidiform mole (HM) significantly improves diagnostic accuracy over
      histopathology and immunohistochemical analysis alone, particularly in the
      classification of partial mole. However, the implementation of this advance in
      diagnostics has been slow. This study sought to identify the major benefit and
      potential barriers to the adoption of genotyping. A pilot Placental Molar
      Diagnostic (PMD) Service was established combining histopathology, p57
      immunohistochemistry, and molecular genotyping analysis for both in-house and
      referred-in cases suspicious for HM or with a preliminary diagnosis of HM. A
      retrospective analysis of 117 cases received in the first 16 mo was conducted to
      identify the utility of the PMD Service and factors or barriers which precluded
      optimal results. A final diagnosis of HM was made in 73 cases (37 complete HMs
      and 36 partial HMs). The remaining 44 cases were hydropic abortuses. Three
      potential barriers were identified that could lead to less than optimal results
      from a PMD Service: prevalence of noninformative genotyping, lack of any
      available or appropriate paraffin blocks, and inappropriate deferral of
      genotyping. The major utility of this pilot PMD Service was to increase the
      specificity of a diagnosis of HM, and avoid unnecessary clinical follow-up in 37%
      of cases with an initial suspicion or diagnosis of HM. Measures can be undertaken
      to address potential barriers to the implementation of a comprehensive placental
      diagnostic platform. Underutilization of molecular genotyping in the diagnosis of
      HM likely leads to inappropriate management and "downstream" costs in a
      significant proportion of patients suspected of having HM. 

PMID- 25851708
TI  - A Case of Vulval Extramammary Paget Disease With Dermal Invasion Showing Mucinous
      Carcinoma.
AB  - We report a case of vulval extramammary Paget disease (EMPD) with dermal invasion
      showing mucinous carcinoma (MC). An 80-year-old woman presented with vulvar
      itching and pain. A physical examination showed a pigmented vulvar, perianal
      erythematous plague, and a subcutaneous nodule in the left major labia. No
      internal malignancy, such as colorectal or genitourinary carcinoma, was
      identified in any of the clinical examinations. A histological examination of the
      resected specimen revealed Pagetoid tumor cells that had spread widely through
      the epidermis and invaded the dermis forming a solid nest with mucous lake-like
      MC. Immunohistochemical examination revealed that the tumor cells in the
      epidermis and dermis were positive for CK7, CEA, GCDFP-15, MUC5AC, and MUC2, but
      negative for CK20, MUC6, and CDX2. Only the invasive component showed
      overexpression of p53. A diagnosis of primary EMPD with dermal invasion showing
      MC of the vulva was made. This is an extremely rare diagnosis, and we suggest
      that immunohistochemical evaluations in addition to systemic work-ups are helpful
      in distinguishing between these cases and those involving vulvar or perianal skin
      invasion of underlying colorectal or genitourinary carcinomas, which are referred
      to as secondary EMPD. 

PMID- 25851709
TI  - Ovarian Hemangiomas Do Not Harbor EWSR1 Rearrangements: Clinicopathologic
      Characterization of 10 Cases.
AB  - Hemangiomas of the ovary are rare with a majority described as individual reports
      of unusual clinical presentations or morphologic findings. Both the expected and
      unexpected pathologic features of these tumors in the ovary are not well
      detailed. Therefore, we collected the largest series of ovarian hemangiomas to
      comprehensively define their clinicopathologic associations and examine the
      significance of hormone receptors in their pathogenesis. In addition, a novel
      EWSR1-NFATC1 fusion has recently been described in a case of hemangioma of bone.
      To our knowledge, EWSR1 rearrangement has not been evaluated in hemangiomas of
      other sites or in a case series. Accordingly, we used fluorescence in situ
      hybridization to investigate EWSR1 status in a majority of our cases. Clinical
      presentation was variable and dependent on tumor size. Patient age ranged 48 to
      87 yr (median 63 yr). Tumors involved the right (n=6) and left (n=3) ovaries with
      laterality unknown in 1 case, and size ranged from 0.2 to 5.0 cm (median 1.0 cm).
      Three of 4 radiologic reports were either equivocal or could not exclude
      malignancy. Seven cases were of the cavernous type and 3 were mixed cavernous and
      capillary type. All lesions formed a single discrete, circumscribed mass that
      displaced the surrounding cortical stroma. The cavernous type showed dilated,
      thin-walled vessels and vascular thrombi, some of which were associated with
      dystrophic calcification. In addition to cavernous morphology, the mixed form
      exhibited features of capillary hemangioma such as lobulated growth of capillary
      sized vascular spaces that lacked atypia or multilayering and were linked to a
      larger feeding vessel. Each tumor expressed CD31, CD34, FLI-1, ERG, but not D240.
      The hemangioma stromal cells, but not endothelium, expressed estrogen and
      progesterone receptors in every case. Stromal luteinization was seen in 2 cases.
      Follow-up ranged 1 to 139 mo and all patients were disease free. All cases were
      negative for EWSR1 rearrangement; however, 2 cases demonstrated additional intact
      copies of EWSR1 indicating aneusomy 22 or a structural abnormality of chromosome
      22 resulting in apparent duplication of the EWSR1 gene region (at 22q12).
      Although an uncommon entity, awareness of ovarian hemangioma's unique and diverse
      clinical presentation as well as its potential to radiologically imitate
      malignant ovarian neoplasms are important. 

PMID- 25851710
TI  - "Pseudomyxoma Endometrii": Endometrial Deposition of Acellular Mucin from a Low
      Grade Appendiceal Mucinous Neoplasm as a Rare Mimic of Myxoid Uterine Tumors.
AB  - Low-grade appendiceal mucinous neoplasms (LAMNs) are commonly associated with
      deposition of mucin, with or without admixed low-grade epithelium, on peritoneal
      surfaces (pseudomyxoma peritonei). We describe a very rare presentation of LAMN
      as extensive mucin deposition in the endometrium of a 43-yr-old woman initially
      mistaken for a primary uterine myxoid neoplasm. The patient underwent endometrial
      curettage that demonstrated abundant myxoid/mucoid material interspersed with
      small vessels, bland eosinophilic spindled cells, scattered foci of typical
      endometrial stroma, and occasional endometrioid glands. The endometrial stroma
      was positive for CD10, and the eosinophilic spindled cells were positive for
      actin. The lesion was interpreted as "myxoid/mucinous neoplasm, most likely of
      smooth muscle/endometrial stromal origin." Subsequent laparotomy revealed
      peritoneal mucin in the anterior cul-de-sac and a dilated appendix. Pathologic
      review confirmed appendiceal LAMN and multifocal peritoneal mucinosis. The uterus
      contained scant residual mucoid material. On review of all pathologic material at
      our institution, the endometrial lesion was consistent with organizing mucin
      derived from the LAMN with entrapped benign endometrium. "Pseudomyxoma
      endometrii" is readily mistaken for a primary uterine myxoid neoplasm,
      particularly myxoid endometrial stromal tumor. A key to diagnosis is recognition
      that the material is mucin rather than myxoid stroma. This is evidenced by the
      absence of embedded stromal cells and presence of myofibroblastic, vascular, and
      macrophage infiltration associated with organization. Epithelium containing
      goblet cells is an important clue if present. The presence of rare endometrial
      glands within the endometrial stroma suggests that the latter is entrapped rather
      than neoplastic. 

PMID- 25851711
TI  - Differential Expression Patterns of GATA3 in Uterine Mesonephric and
      Nonmesonephric Lesions.
AB  - GATA binding protein 3 (GATA3) is a recently described immunohistochemical marker
      that has proven useful in the characterization of breast and urothelial
      carcinomas. However, the expression pattern of GATA3 in mesonephric
      proliferations is largely unknown. The aim of this study was to examine the
      immunohistochemical expression of GATA3 in cervicovaginal mesonephric lesions and
      compare it to its expression in endocervical and endometrial adenocarcinomas and
      cervicovaginal endometriosis. A cohort of 107 cases, including 33 cases of
      mesonephric lesions and 74 cases of nonmesonephric lesions, was selected for the
      study. Of 33 mesonephric lesions, 31 (94%) cases (16 remnants, 12 hyperplasias,
      and 3 adenocarcinomas) were strongly and diffusely positive in tumor cell nuclei
      for GATA3. The remaining 2 mesonephric carcinosarcomas showed focal nuclear
      staining and rare nuclear positivity, respectively. Of 36 endocervical
      adenocarcinomas, 33 (92%) were negative for GATA3 and the remaining revealed
      focal weak nuclear staining. Of 34 endometrial adenocarcinomas, 32 (94%) were
      negative, whereas 2 showed rare nuclear positivity. All 4 cases of endometriosis
      were negative. The benign endocervical epithelium and the benign endometrium in
      most cases lacked GATA3 expression, whereas the benign squamous epithelium in the
      majority exhibited nuclear basal and parabasal staining pattern. Our study
      demonstrates that GATA3 protein is expressed in most mesonephric lesions,
      regardless of them being benign or malignant. In contrast, GATA3 is absent in the
      majority of endometrial and endocervical adenocarcinomas. These results support
      that GATA3 immunostain can be a useful tool in differentiating mesonephric
      lesions from endocervical and endometrial adenocarcinomas. 

PMID- 25851712
TI  - Vulvar Myxoid Liposarcoma and Well Differentiated Liposarcoma With Molecular
      Cytogenetic Confirmation: Case Reports With Review of Malignant Lipomatous Tumors
      of the Vulva.
AB  - Malignant lipomatous tumors of the vulva are uncommon. We present 2 cases of
      liposarcoma arising in the vulva: a myxoid liposarcoma harboring DDIT3 and FUS
      rearrangements and a well differentiated liposarcoma/atypical lipomatous tumor
      harboring MDM2 amplification detected by fluorescence in situ hybridization. Both
      cases are the first liposarcomas of this site to be confirmed by molecular
      cytogenetic analysis. We also review the literature's cases of liposarcoma to
      further examine the clinicopathologic features of these tumors. 

PMID- 25851713
TI  - Defective DNA Mismatch Repair Influences Expression of Endometrial Carcinoma
      Biomarkers.
AB  - Endometrial endometrioid carcinomas are related to estrogen excess and express
      estrogen and progesterone receptors. However, hormone receptor expression can be
      variable from tumor to tumor, and this variability is not always explained by
      differences in tumor grade. Variable expression of other biomarkers that may be
      used in the diagnostic work-up of endometrial cancer has also been noted. We
      hypothesized that mismatch repair (MMR) defects may contribute to this
      variability. A total of 411 unselected endometrial carcinomas were evaluated for
      immunohistochemical expression of DNA MMR proteins and MLH1 methylation. Loss of
      immunohistochemical expression of MLH1, MSH2, MSH6, or PMS2 was defined as MMR
      deficient; positive expression was defined as MMR intact. A case-control cohort
      of 80 Grade 2 endometrioid carcinomas was selected from this set (40 MMR
      deficient, 40 MMR intact). Cases were matched for histotype, grade, and age.
      Estrogen receptor, progesterone receptor, CK7(+), CK20, and Pax-8
      immunohistochemistry was evaluated. The median percentage of CK7 tumor cells was
      significantly lower in the MMR deficient group compared with the MMR intact
      group. The mean percentage of tumor cells exhibiting estrogen receptor expression
      was similar in both the MMR-deficient and MMR intact groups. However, there was
      greater variability in the MMR-deficient group. Our study shows that MMR defects
      influence the expression of clinically important biomarkers for endometrioid-type
      endometrial carcinoma as decreased cytokeratin 7 expression is more commonly
      associated with MMR deficiency.

PMID- 25851714
TI  - Identifying palliative care issues in inpatients dying following stroke.
AB  - BACKGROUND: Stroke leads to high mortality and morbidity but often there is a
      conflict between need for palliative care and avoidance of 'therapeutic
      nihilism'. AIMS: We aimed to elicit the palliative care needs of stroke patients
      at the end of their lives in our unit with a low overall mortality rate (1 month:
      8.8 %, inpatient: 12.9 %). METHODS: We identified consecutive stroke patients who
      died over 2 years. Their clinical records were used for data collection. RESULTS:
      Of 54 deaths, 33 (61.1 %) were females, mean (SD) age at death was 79.3 +/- 12.9
      years. 41 (75.9 %) died after first stroke, 9 (16.7 %) were inpatient strokes, 7
      (13.0 %) thrombolysed and 7 (13.0 %) had strokes as treatment complication. There
      were clear statements recorded in 26 (48.1 %) that patients were dying and death
      was thought to be due primarily to extent of brain injury in 24 (44.4 %).
      Palliative needs identified included dyspnoea 21 (38.9 %), pain 17 (31.5 %),
      respiratory secretions 17 (31.5 %), agitation 14 (25.9 %) and psychological
      distress 1 (1.9 %). Symptoms were due to premorbid diseases in 6 (11.1 %).
      Palliative care expertise were sought in 13 (24.1 %) and continuous subcutaneous
      infusion was used in 18 (33.3 %) to control symptoms. 4 (7.4 %) subjects
      underwent cardiac arrest calls and 9 (16.7 %) deaths occurred in ICU/HDU. The
      median Stroke-Death interval was 20 days (range 0-389). Do Not Attempt
      Resuscitation (DNAR) orders were in place in 86.8 % of patients. The median DNAR
      Death interval was 7 days (range 0-311) with 7-day DNAR-Death rate of 53.2 % and
      30-day of 78.7 % of the total deaths. CONCLUSIONS: Dyspnoea, pain and respiratory
      secretions were identified as the main palliative care needs.

PMID- 25851716
TI  - Stepwise optimization of a low-temperature Bacillus subtilis expression system
      for "difficult to express" proteins.
AB  - In order to improve the overproduction of "difficult to express" proteins, a low
      temperature expression system for Bacillus subtilis based on the cold-inducible
      promoter of the desaturase-encoding des gene was constructed. Selected regulatory
      DNA sequence elements from B. subtilis genes known to be cold-inducible were
      fused to different model genes. It could be demonstrated that these regulatory
      elements are able to mediate increased heterologous gene expression, either by
      improved translation efficiency or by higher messenger RNA (mRNA) stability. In
      case of a cold-adapted beta-galactosidase from Pseudoalteromonas haloplanktis
      TAE79A serving as the model, significantly higher expression was achieved by
      fusing its coding sequence to the so-called "downstream box" sequence of cspB
      encoding the major B. subtilis cold-shock protein. The combination of this fusion
      with a cspB 5'-UTR stem-loop structure resulted in further enhancement of the
      beta-galactosidase expression. In addition, integration of the transcription
      terminator of the B. subtilis cold-inducible bkd operon downstream of the target
      genes caused a higher mRNA stability and enabled thus a further significant
      increase in expression. Finally, the fully optimized expression system was
      validated by overproducing a B. subtilis xylanase as well as an alpha-glucosidase
      from Saccharomyces cerevisiae, the latter known for tending to form inclusion
      bodies. These analyses verified the applicability of the engineered expression
      system for extracellular and intracellular protein synthesis in B. subtilis,
      thereby confirming the suitability of this host organism for the overproduction
      of critical, poorly soluble proteins. 

PMID- 25851717
TI  - Reconstruction of the carnitine biosynthesis pathway from Neurospora crassa in
      the yeast Saccharomyces cerevisiae.
AB  - Industrial synthesis of L-carnitine is currently performed by whole-cell
      biotransformation of industrial waste products, mostly D-carnitine and
      cronobetaine, through specific bacterial species. No comparable system has been
      established using eukaryotic microorganisms, even though there is a significant
      and growing international demand for either the pure compound or carnitine
      enriched consumables. In eukaryotes, including the fungus Neurospora crassa, L
      carnitine is biosynthesized through a four-step metabolic conversion of
      trimethyllysine to L-carnitine. In contrast, the industrial yeast, Saccharomyces
      cerevisiae lacks the enzymes of the eukaryotic biosynthesis pathway and is unable
      to synthesize carnitine. This study describes the cloning of all four of the N.
      crassa carnitine biosynthesis genes and the reconstruction of the entire pathway
      in S. cerevisiae. The engineered yeast strains were able to catalyze the
      synthesis of L-carnitine, which was quantified using hydrophilic interaction
      liquid chromatography electrospray ionization mass spectrometry (HILIC-ESI-MS)
      analyses, from trimethyllysine. Furthermore, the yeast threonine aldolase Gly1p
      was shown to effectively catalyze the second step of the pathway, fulfilling the
      role of a serine hydroxymethyltransferase. The analyses also identified yeast
      enzymes that interact with the introduced pathway, including Can1p, which was
      identified as the yeast transporter for trimethyllysine, and the two yeast serine
      hydroxymethyltransferases, Shm1p and Shm2p. Together, this study opens the
      possibility of using an engineered, carnitine-producing yeast in various
      industrial applications while providing insight into possible future strategies
      aimed at tailoring the production capacity of such strains. 

PMID- 25851715
TI  - Enhanced C30 carotenoid production in Bacillus subtilis by systematic
      overexpression of MEP pathway genes.
AB  - Creating novel biosynthetic pathways and modulating the synthesis of important
      compounds are one of the hallmarks of synthetic biology. Understanding the key
      parameters controlling the flux of chemicals throughout a metabolic pathway is
      one of the challenges ahead. Isoprenoids are the most functionally and
      structurally diverse group of natural products from which numerous medicines and
      relevant fine chemicals are derived. The well-characterized and broadly used
      production organism Bacillus subtilis forms an ideal background for creating and
      studying novel synthetic routes. In comparison to other bacteria, B. subtilis
      emits the volatile compound isoprene, the smallest representative of isoprenoids,
      in high concentrations and thus represents an interesting starting point for an
      isoprenoid cell factory. In this study, the effect of systematic overexpression
      of the genes involved in the methylerythritol phosphate (MEP) pathway on
      isoprenoid production in B. subtilis was investigated. B. subtilis strains
      harboring a plasmid containing C30 carotenoid synthetic genes, crtM and crtN,
      were combined with pHCMC04G plasmids carrying various synthetic operons of the
      MEP pathway genes. The levels of produced carotenoids, diaponeurosporene and
      diapolycopene, were used as indication of the role of the various enzymes on the
      flux of the MEP pathway. It was shown that the production of carotenoids can be
      increased significantly by overexpressing the MEP pathway enzymes. More broadly,
      the strains developed in this study can be used as a starting point for various
      isoprenoid cell factories. 

PMID- 25851718
TI  - Metabolic engineering of Clostridium tyrobutyricum for n-butanol production:
      effects of CoA transferase.
AB  - The overexpression of CoA transferase (ctfAB), which catalyzes the reaction:
      acetate/butyrate + acetoacetyl-CoA -> acetyl/butyryl-CoA + acetoacetate, was
      studied for its effects on acid reassimilation and butanol biosynthesis in
      Clostridium tyrobutyricum (Deltaack, adhE2). The plasmid pMTL007 was used to co
      express adhE2 and ctfAB from Clostridium acetobutylicum ATCC 824. In addition,
      the sol operon containing ctfAB, adc (acetoacetate decarboxylase), and ald
      (aldehyde dehydrogenase) was also cloned from Clostridium beijerinckii NCIMB 8052
      and expressed in C. tyrobutyricum (Deltaack, adhE2). Mutants expressing these
      genes were evaluated for their ability to produce butanol from glucose in batch
      fermentations at pH 5.0 and 6.0. Compared to C. tyrobutyricum (Deltaack, adhE2)
      without expressing ctfAB, all mutants with ctfAB overexpression produced more
      butanol, with butanol yield increased to 0.22 - 0.26 g/g (vs. 0.10 - 0.13 g/g)
      and productivity to 0.35 g/l h (vs. 0.13 g/l h) because of the reduced acetate
      and butyrate production. The expression of ctfAB also resulted in acetone
      production from acetoacetate through a non-enzymatic decarboxylation. 

PMID- 25851719
TI  - Characterization of a bioflocculant from potato starch wastewater and its
      application in sludge dewatering.
AB  - A bioflocculant was produced by using potato starch wastewater; its potential in
      sludge dewatering and potato starch wastewater treatment was investigated.
      Production of this bioflocculant was positively associated with cell growth, and
      a highest value of 0.81 g/L was obtained. When incubated with this bioflocculant,
      dry solids (DS) and specific resistance to filtration (SRF) of typical wastewater
      activated sludge reached 20.8% and 3.9 * 10(12) m/kg, respectively, which were
      much better than the ones obtained with conventional chemical flocculants. Sludge
      dewatering was further improved when both the bioflocculant and conventional
      polyacrylamide (PAM) were used simultaneously. With potato starch wastewater,
      chemical oxygen demand (COD) and turbidity removal rates could reach 52.4 and
      81.7%, respectively, at pH value of 7.5 when the bioflocculant dose was adjusted
      to 30 mg/L; from a practical standpoint, the removal of COD and turbidity reached
      48.3 and 72.5%, respectively, without pH value adjustment.

PMID- 25851720
TI  - The British Society for Haematology: 'What have the Romans ever done for us?'.
AB  - '....Alright, but apart from the sanitation, medicine, education, wine, public
      order, irrigation, the roads, fresh water and public health..................what
      have the Romans ever done for us?' From Monty Python's Life of Brian An
      organizational review of the British Society for Haematology (BSH) was started in
      November 2013 and completed in June 2014. Many members of the Society
      participated in the surveys and have given their views, including those on the
      Shape of Training Greenaway report. Members' views were incorporated in the
      review and these have informed the eight strategic aims agreed at the Board
      meeting on 10 June 2014. The BSH will aim to realise these strategic aims over
      the next three to five years.

PMID- 25851722
TI  - Correlation between the molecular structure and the kinetics of decomposition of
      azamacrocyclic copper(ii) complexes.
AB  - The formation of copper(ii) complexes with symmetrical dinucleating macrocyclic
      ligands containing two either monomethylated () or trimethylated ()
      diethylenetriamine (Medien or Me3dien) subunits linked by pyridine spacers has
      been studied by potentiometry. Potentiometric studies show that has larger
      basicity than as well as higher stability of its mono- and binuclear complexes.
      The crystal structures of .6HCl (), [Cu2(L1)Cl2](CF3SO3)2 (),
      [Cu2(L1)(OH)](ClO4)3.3H2O () and [Cu(L1)](ClO4)2 () show that adopts different
      coordination modes when bound to copper(ii). Whereas in , each copper(ii) is
      bound to one Medien subunit and to one pyridine group, in each metal center is
      coordinated to one 2,6-di(aminomethyl)pyridine moiety (damp) and to one
      aminomethyl group. The mononuclear complex shows pseudo-octahedral coordination
      with two weakly coordinated axial nitrogens. Kinetic studies indicate that
      complex decomposition is strongly dependent on the coordination mode of . Upon
      addition of an acid excess, all the species except [Cu2(L1)](4+) convert very
      rapidly to an intermediate that decomposes more slowly to copper(ii) and a
      protonated ligand. In contrast, [Cu2(L1)](4+) decomposes directly without the
      formation of any detectable intermediate. These results can be rationalized by
      considering that the crystal structures are maintained in solution and that the
      weakest Cu-N bonds are broken first, thus indicating that kinetic measurements on
      complex decomposition can be used to provide information about structural
      reorganizations in the complexes. In any case, complete decomposition of the
      complexes takes place in a maximum of two kinetically resolvable steps. However,
      minor changes in the structure of the complexes can lead to drastic changes in
      the kinetics of decomposition and the complexes decompose with polyphasic
      kinetics in which up to four different steps associated with the successive
      breaking of the different Cu-N bonds can be resolved. 

PMID- 25851721
TI  - Impact of medical education program on COPD patients: a cohort prospective study.
AB  - BACKGROUND: The main objective of this study was to assess the effects of
      intensive medical education courses on chronic obstructive pulmonary disease
      (COPD)-related rehospitalizations and emergency department visits and the
      secondary aim was to monitor quality of life. METHODS: This cohort prospective
      study included 76 group D COPD patients (pts.). Patients from the intervention
      group (IG, 52 pts.) underwent a program comprising two components: a
      comprehensive medical education program (1h/day for 5 days) and a specific drug
      therapy. Control group (CG, 24 pts.) received only drug therapy. Patients
      underwent spirometry and completed St. George's Respiratory Questionnaire (SGRQ)
      at the time of inclusion and at periodical evaluations performed every three
      months for a year. RESULTS: Patients included in a medical education program
      showed significant decrease of exacerbation rate compared with the CG. Patients
      from the IG group had fewer emergency department visits within a year compared
      with the CG. Patients from the IG had significantly better quality of life scores
      (both at 3 and 6 months) compared with the CG. CONCLUSIONS: This study reveals
      that an adequate medical education program is associated with a decreased rate of
      COPD-related hospitalizations. The implementation of a medical education program
      as an integrated part of therapy could lead to a more accurate self-management of
      the disease.

PMID- 25851723
TI  - JAGN1 Deficient Severe Congenital Neutropenia: Two Cases from the Same Family.
AB  - Recently autosomal recessively inherited mutations in the gene encoding Jagunal
      homolog 1 (JAGN1) was described as a novel disease-causing gene of severe
      congenital neutropenia (SCN) JAGN1-mutant neutrophils were characterized by
      abnormality in endoplasmic reticulum structure, absence of granules, abnormal N
      glycosylation of proteins and susceptibility to apoptosis. These findings imply
      the role of JAGN1 in neutrophil survival. Here, we report two siblings with a
      homozygous mutation in JAGN1 gene, exhibiting multisystemic involvement. 

PMID- 25851725
TI  - Diversity and antifungal activity of the endophytic fungi associated with the
      native medicinal cactus Opuntia humifusa (Cactaceae) from the United States.
AB  - The endophytic fungal community associated with the native cactus Opuntia
      humifusa in the United States was investigated and its potential for providing
      antifungal compounds. A hundred-eight endophytic fungal isolates were obtained
      and identified by molecular methods into 17 different taxa of the genera
      Alternaria, Aureobasidium, Biscogniauxia, Cladosporium, Cryptococcus, Curvularia,
      Diaporthe, Epicoccum, Paraconiothyrium, Pestalotiopsis and Phoma. The most
      frequent species associated with O. humifusa were Alternaria sp. 3, Aureobasidium
      pullulans and Diaporthe sp. The fungal community of O. humifusa had a high
      richness and diversity; additionally, the species richness obtained indicates
      that the sample effort was enough to recover the diversity pattern obtained. Six
      extracts of endophytes showed antifungal properties and (1)H NMR analyses of the
      extracts of Alternaria sp. 5 Ohu 8B2, Alternaria sp. 3 Ohu 30A, Cladosporium
      funiculosum Ohu 17C1 and Paraconiothyrium sp. Ohu 17A indicated the presence of
      functional groups associated with unsaturated fatty-acid olefinic protons and
      fatty acid methylene and methyl protons. GC-FID analysis of these extracts
      confirmed the presence of a mixture of different fatty acids. The (1)H NMR
      analyses of Biscogniauxia mediterranea Ohu 19B extracts showed the presence of
      aromatic compounds. From the extract of B. mediterranea we isolated the compound
      5-methylmellein that displayed moderate antifungal activity against the
      phytopathogenic fungi Phomopsis obscurans. Our results suggest that native
      medicinal cacti of the United States can live symbiotically with rich and diverse
      endophytic communities and may be a source of bioactive molecules, including
      those able to inhibit or control plant disease pathogens. 

PMID- 25851726
TI  - Alterations in the expression of genes related to contractile function and
      hypertrophy of the left ventricle in chronically paced patients from the right
      ventricular apex.
AB  - AIM: Long-term right ventricular apical (RVA) pacing may lead to left ventricular
      (LV) remodelling and heart failure. This study assessed changes in the expression
      of genes regulating LV contractile function and hypertrophy, after permanent RVA
      pacing and investigated whether such changes proceed or even predict LV
      remodelling. METHODS AND RESULTS: We enrolled 52 consecutive patients (age 79.1
      +/- 7.7 years, 34 males) who underwent pacemaker implantation for bradycardic
      indications: Group A, 24 individuals with atrioventricular conduction
      disturbances and group B, 28 patients with sinus node disease. In group A,
      peripheral blood mRNA levels of gene sarcoplasmic reticulum calcium ATPase
      decreased at 3, 6, and 12 months' follow-up, while alpha-myosin heavy chain (MHC)
      decreased and beta-MHC increased until 6 months follow-up. In this group, 25% of
      patients demonstrated significant LV remodelling. At 4 years, LV end-systolic
      diameter increased from 29.67 +/- 3.39 mm at baseline to 35.38 +/- 4.22 mm, LV
      end-diastolic diameter increased from 50 +/- 4.95 to 56.71 +/- 5.52 mm, and
      ejection fraction declined from 63.04 +/- 10.22 to 52.83 +/- 10.81%. Early
      alterations in gene expression were associated with a deterioration in LV
      function and geometry that became apparent months later. In group B,
      echocardiographic indexes and mRNA levels of the evaluated genes demonstrated no
      statistically significant changes. CONCLUSIONS: Permanent RVA pacing in patients
      with preserved ejection fraction is associated with alterations in the expression
      of genes regulating LV contractile function and hypertrophy, measured in the
      peripheral blood. These alterations are traceable at an early stage, before
      echocardiographic changes are apparent and are associated with LV remodelling
      that becomes evident in the long term.

PMID- 25851727
TI  - Why Accurate Knowledge of Zygosity is Important to Twins.
AB  - All same-sex dizygotic (DZ) twins and approximately one-third of monozygotic (MZ)
      twin pairs have separate placentas, making it impossible to use the number of
      placentas to determine zygosity. Zygosity determination is further complicated
      because incorrect assumptions are often made, such as that only DZ pairs have two
      placentas and that all MZ pairs are phenotypically identical. These assumptions,
      by twins, their families and health professionals, along with the lack of
      universal zygosity testing for same-sex twins, has led to confusion within the
      twin community, yet little research has been conducted with twins about their
      understanding and assumptions about zygosity. We aimed to explore and quantify
      understanding and assumptions about zygosity using twins attending an Australian
      twin festival. We recruited 91 twin pairs younger than 18 years of age and their
      parents, and 30 adult twin pairs who were all uncertain of their zygosity, to
      complete one pen and paper questionnaire and one online questionnaire about their
      assumed zygosity, reasons for their assumptions and the importance of accurate
      zygosity knowledge. Responses were compared with their true zygosity measured
      using a genetic test. We found a substantial proportion of parents and twins had
      been misinformed by their own parents or medical professionals, and that
      knowledge of their true zygosity status provided peace of mind and positive
      emotional responses. For these reasons we propose universal zygosity testing of
      same-sex twins as early in life as possible and an increase in education of
      medical professionals, twins and families of twins about zygosity issues. 

PMID- 25851728
TI  - The microbiota and microbiome in aging: potential implications in health and age
      related diseases.
AB  - Advances in bacterial deoxyribonucleic acid sequencing allow for characterization
      of the human commensal bacterial community (microbiota) and its corresponding
      genome (microbiome). Surveys of healthy adults reveal that a signature composite
      of bacteria characterizes each unique body habitat (e.g., gut, skin, oral cavity,
      vagina). A myriad of clinical changes, including a basal proinflammatory state
      (inflamm-aging), that directly interface with the microbiota of older adults and
      enhance susceptibility to disease accompany aging. Studies in older adults
      demonstrate that the gut microbiota correlates with diet, location of residence
      (e.g., community dwelling, long-term care settings), and basal level of
      inflammation. Links exist between the microbiota and a variety of clinical
      problems plaguing older adults, including physical frailty, Clostridium difficile
      colitis, vulvovaginal atrophy, colorectal carcinoma, and atherosclerotic disease.
      Manipulation of the microbiota and microbiome of older adults holds promise as an
      innovative strategy to influence the development of comorbidities associated with
      aging. 

PMID- 25851729
TI  - A minimal standardization setting for language mapping tests: an Italian example.
AB  - During awake surgery, picture-naming tests are administered to identify brain
      structures related to language function (language mapping), and to avoid
      iatrogenic damage. Before and after surgery, naming tests and other
      neuropsychological procedures aim at charting naming abilities, and at detecting
      which items the subject can respond to correctly. To achieve this goal,
      sufficiently large samples of normed and standardized stimuli must be available
      for preoperative and postoperative testing, and to prepare intraoperative tasks,
      the latter only including items named flawlessly preoperatively. To discuss
      design, norming and presentation of stimuli, and to describe the minimal
      standardization setting used to develop two sets of Italian stimuli, one for
      object naming and one for verb naming, respectively. The setting includes a
      naming study (to obtain picture-name agreement ratings), two on-line
      questionnaires (to acquire age-of-acquisition and imageability ratings for all
      test items), and the norming of other relevant language variables. The two sets
      of stimuli have >80 % picture-name agreement, high levels of internal consistency
      and reliability for imageability and age of acquisition ratings. They are normed
      for psycholinguistic variables known to affect lexical access and retrieval, and
      are validated in a clinical population. This framework can be used to increase
      the probability of reliably detecting language impairments before and after
      surgery, to prepare intraoperative tests based on sufficient knowledge of pre
      surgical language abilities in each patient, and to decrease the probability of
      false positives during surgery. Examples of data usage are provided. Normative
      data can be found in the supplementary materials.

PMID- 25851730
TI  - An inverse association between serum vitamin D levels with the presence and
      severity of impaired nerve conduction velocity and large fiber peripheral
      neuropathy in diabetic subjects.
AB  - Diabetic neuropathy (DN) is the most common complication of diabetes mellitus
      (DM) and also the major cause of morbidity and mortality in diabetic patients.
      There have been recent speculations that circulating 25-hydroxyvitamin D (25(OH)
      D) could be involved in DN development and progression. This study explored the
      association between serum 25(OH)-D and DN in diabetic subjects by performing
      strict matching of possible confounders. Overall, 33 diabetic subjects with DN
      and 29 controls matched in terms of age, sex, BMI, height and disease duration
      entered this study. Nerve conduction velocity (NCV) was performed to determine
      the existence and severity of large fiber neuropathy. 25(OH)-D had significantly
      lower value in DN group (21.2 +/- 11.5 vs. 13.5 +/- 5.1 ng/mL, P = 0.001). None
      of the other observed variables showed a significant association with existence
      and severity of DN. After adjustment for all studied variables, serum vitamin D
      had an independent and inverse association with both DN presence and severity, as
      each 1 ng/mL increase in serum 25(OH)-D was correlated with 2.2 and 3.4 %
      decrease in the presence and severity of NCV impairment, respectively. While
      adjusted for demographic variables, comorbidities and treatment of DM, our
      results imply that decreased levels of circulating 25(OH)-D may contribute to
      increased risk of large fiber neuropathy in type 2 diabetic subjects.

PMID- 25851731
TI  - Usual coffee intake in Brazil: results from the National Dietary Survey 2008-9.
AB  - Coffee is central to the economy of many developing countries, as well as to the
      world economy. However, despite the widespread consumption of coffee, there are
      very few available data showing the usual intake of this beverage. Surveying
      usual coffee intake is a way of monitoring one aspect of a population's usual
      dietary intake. Thus, the present study aimed to characterise the usual daily
      coffee intake in the Brazilian population. We used data from the National Dietary
      Survey collected in 2008-9 from a probabilistic sample of 34,003 Brazilians aged
      10 years and older. The National Cancer Institute method was applied to obtain
      the usual intake based on two nonconsecutive food diaries, and descriptive
      statistical analyses were performed by age and sex for Brazil and its regions.
      The estimated average usual daily coffee intake of the Brazilian population was
      163 (SE 2.8) ml. The comparison by sex showed that males had a 12% greater usual
      coffee intake than females. In addition, the highest intake was recorded among
      older males. Among the five regions surveyed, the North-East had the highest
      usual coffee intake (175 ml). The most common method of brewing coffee was
      filtered/instant coffee (71%), and the main method of sweetening beverages was
      with sugar (87%). In Brazil, the mean usual coffee intake corresponds to 163 ml,
      or 1.5 cups/d. Differences in usual coffee intake according to sex and age
      differed among the five Brazilian regions.

PMID- 25851732
TI  - Performance status and depressive symptoms as predictors of quality of life in
      cancer patients. A structural equation modeling analysis.
AB  - OBJECTIVE: This study aimed to examine whether depressive symptoms and
      performance status are independent predictors of both the physical and
      psychological domains of health-related quality of life (HRQoL) in cancer
      patients. METHODS: A sample of 4020 cancer patients (mean age 58 years, 51%
      women) was evaluated. Depressive symptoms were measured with the patient health
      questionnaire and HRQoL with the European Organisation for Research and Treatment
      of Cancer quality of life questionnaire core 30. The impact of the illness on
      everyday activities was assessed with physician ratings of both the Karnofsky
      performance status and the Eastern Cooperative Oncology Group performance status.
      The simultaneous effects of depression and performance status on quality of life
      outcomes were estimated using structural equation modeling. RESULTS: Both
      depressive symptoms and performance status independently predicted the physical
      and psychological domains of HRQoL. However, the impact of depressive symptoms on
      the physical HRQoL was stronger than the impact of performance status on the
      psychological HRQoL. CONCLUSION: Our results suggest that comorbid depressive
      symptoms are independently associated with both physical and psychological HRQoL
      in cancer patients after controlling for the physician-rated performance status.
      Thus, comorbid depression should be taken into account when evaluating reduced
      HRQoL in cancer patients. To support a causal impact of depression on HRQoL,
      intervention studies are needed to show that improving depression enhances cancer
      patients' HRQoL.

PMID- 25851733
TI  - Making big communities small: using network science to understand the ecological
      and behavioral requirements for community social capital.
AB  - The concept of social capital is becoming increasingly common in community
      psychology and elsewhere. However, the multiple conceptual and operational
      definitions of social capital challenge its utility as a theoretical tool. The
      goals of this paper are to clarify two forms of social capital (bridging and
      bonding), explicitly link them to the structural characteristics of small world
      networks, and explore the behavioral and ecological prerequisites of its
      formation. First, I use the tools of network science and specifically the concept
      of small-world networks to clarify what patterns of social relationships are
      likely to facilitate social capital formation. Second, I use an agent-based model
      to explore how different ecological characteristics (diversity and segregation)
      and behavioral tendencies (homophily and proximity) impact communities' potential
      for developing social capital. The results suggest diverse communities have the
      greatest potential to develop community social capital, and that segregation
      moderates the effects that the behavioral tendencies of homophily and proximity
      have on community social capital. The discussion highlights how these findings
      provide community-based researchers with both a deeper understanding of the
      contextual constraints with which they must contend, and a useful tool for
      targeting their efforts in communities with the greatest need or greatest
      potential.

PMID- 25851734
TI  - Effect of hepatic insulin expression on lipid metabolism in diabetic mice.
AB  - BACKGROUND: Hypertriglyceridemia is a common lipid disorder that is characterized
      by elevated plasma levels of triglyceride (TG)-rich particles, such as very low
      density lipoprotein (VLDL), in poorly controlled diabetes. The aim of the present
      study was to determine the potential therapeutic effect of hepatic insulin
      production on hypertriglyceridemia in mice. METHODS: Mice were induced diabetic
      and hypertriglyceridemic by streptozotocin (STZ) treatment. Using an adenovirus
      mediated gene transfer approach, we delivered rat preproinsulin cDNA into the
      liver of diabetic mice and then determined plasma TG metabolism. To investigate
      the mechanism by which hepatic insulin improves TG metabolism, we determined
      hepatic expression of apolipoprotein C-III (ApoC-III), a structural moiety and
      functional inhibitor of VLDL-TG catabolism. RESULTS: Plasma VLDL-TG levels were
      markedly elevated in STZ-treated mice, and were accompanied by hyperglycemia and
      hypertriglyceridemia. These metabolic abnormalities were restored to near normal
      following hepatic insulin production in insulin vector-treated diabetic mice. In
      contrast, hypertriglyceridemia and hyperglycemia persisted in control vector
      treated diabetic animals. Hepatic ApoC-III expression became deregulated
      secondary to insulin deficiency, contributing to impaired TG metabolism in
      diabetic mice. Hepatic insulin production suppressed excessive hepatic ApoC-III
      production to basal levels. CONCLUSION: Hepatic insulin production is efficacious
      in correcting hypertriglyceridemia associated with insulin deficiency in diabetic
      mice.

PMID- 25851735
TI  - Parasite host range and the evolution of host resistance.
AB  - Parasite host range plays a pivotal role in the evolution and ecology of hosts
      and the emergence of infectious disease. Although the factors that promote host
      range and the epidemiological consequences of variation in host range are
      relatively well characterized, the effect of parasite host range on host
      resistance evolution is less well understood. In this study, we tested the impact
      of parasite host range on host resistance evolution. To do so, we used the host
      bacterium Pseudomonas fluorescens SBW25 and a diverse suite of coevolved viral
      parasites (lytic bacteriophage Phi2) with variable host ranges (defined here as
      the number of host genotypes that can be infected) as our experimental model
      organisms. Our results show that resistance evolution to coevolved phages
      occurred at a much lower rate than to ancestral phage (approximately 50% vs.
      100%), but the host range of coevolved phages did not influence the likelihood of
      resistance evolution. We also show that the host range of both single parasites
      and populations of parasites does not affect the breadth of the resulting
      resistance range in a naive host but that hosts that evolve resistance to single
      parasites are more likely to resist other (genetically) more closely related
      parasites as a correlated response. These findings have important implications
      for our understanding of resistance evolution in natural populations of bacteria
      and viruses and other host-parasite combinations with similar underlying
      infection genetics, as well as the development of phage therapy.

PMID- 25851736
TI  - Examining the 16-year trajectories of mental health and wellbeing through the
      transition into widowhood.
AB  - BACKGROUND: Becoming widowed is a significant event. There is considerable
      evidence that surviving partners report substantial changes in their wellbeing
      and mental health. Changes can occur prior to partner's death as an anticipatory
      effect and consequently during the period after partner's death. For most,
      declines in wellbeing and mental health dissipate over time. However, there is a
      limited long-term evidence to compare age-normative trajectories in mental health
      and wellbeing with the trajectories of those who transition into widowhood.
      METHODS: Participants (n = 652) were older adults (aged 65-94 years at baseline)
      from the 16-year Melbourne Longitudinal Studies on Healthy Ageing project who
      were either married or de facto (n = 577), or recently widowed (n = 75).
      Generalized Estimating Equations (GEE) examined the immediate and long-term
      impact of widowhood. GEE piecewise regression analyses examined the trajectories
      of wellbeing and mental health in those who transitioned into widowed with time
      centered at time of partner's death. Analyses were stratified by gender. RESULTS:
      For both men and women, becoming widowed was strongly related to a strong decline
      in positive affect post partner's death. Otherwise, no long-term impact of
      widowhood on negative affect or depressive symptomology was reported.
      CONCLUSIONS: The impact of widowhood reports differential impacts on different
      indicators of wellbeing and mental health, which were inconsistent between men
      and women.

PMID- 25851737
TI  - An ultrasensitive electrochemical immunosensor for the detection of CD146 based
      on TiO2 colloidal sphere laden Au/Pd nanoparticles.
AB  - An ultrasensitive electrochemical immunosensor for the detection of cluster of
      differentiation 146 antigen (CD146) based on TiO2 colloidal sphere laden Au/Pd
      nanoparticles (Au/Pd@TiO2) was developed. In this work, reduced graphene oxide
      tetraethylene pentamine (rGO-TEPA) was applied as an electrode modifying material
      to modify the surface of a glassy carbon electrode (GCE). Au/Pd@TiO2 was used as
      the secondary-antibody (Ab2) label for the fabrication of the immunosensor.
      Amperometric response of the immunosensor for electrocatalytic reduction of
      hydrogen peroxide (H2O2) was recorded. Electrochemical impedance spectroscopy
      (EIS) proved that fabrication of the immunosensor was successful. The anti-CD146
      primary antibody (Ab1) was immobilized on the rGO-TEPA modified GCE by a cross
      linking reagent of glutaraldehyde (GA). With Ab1 immobilized onto the rGO-TEPA
      modified GCE and Ab2 linked with Au/Pd@TiO2, the immunosensor displayed a wide
      linear range (0.0050-20 ng mL(-1)), a low detection limit (1.6 pg mL(-1)), good
      reproducibility, good selectivity and acceptable stability. The designed sensing
      strategy may provide a potential application in the detection of other tumor
      markers. 

PMID- 25851738
TI  - Evaluating clinical implications of 15-mega-sub-pixel liquid-crystal display in
      phase-contrast mammography.
AB  - BACKGROUND: Phase-contrast mammography (PCM) systems characteristically yield
      sharp images with edge enhancement and high-resolution 25-MUm/pixel mammograms.
      However, not all PCM image information can be shown on the display at a
      resolution of 5-megapixel (5-MP), although 5-MP monitors are recommended for
      interpretation of digital mammograms. Therefore, we investigated the potential
      utility of a 15-mega-sub-pixel (15-MsP) display for PCM images. METHODS: We used
      a monitor that offered both 5-MP and 15-MsP displays by using a sub-pixel drive
      (SPD) technique to increase the spatial resolution of the monitor by threefold in
      the direction of the sub-pixels. Contrast-detail mammography phantom images were
      evaluated visually by four radiologic technologists. In this study, four display
      magnification ratios were used and the calculated image quality figures (IQFs)
      were compared with those of a 5-MP display. RESULTS: The detection capability of
      the 15-MsP display was significantly better than that of the 5-MP display at
      magnification ratios of 49 and 100 %. At other magnification ratios, the
      detection capability of the 15-MsP display was higher than that of the 5-MP
      display, but the difference was not significant. CONCLUSIONS: A 15-MsP display
      has the potential to provide better detection than that provided by conventional
      5-MP displays. A 15-MsP display using SPD technology is suitable for high
      resolution digital mammograms, such as those produced by PCM systems.

PMID- 25851739
TI  - Latent tuberculosis infection screening in immigrants to low-incidence countries:
      a meta-analysis.
AB  - BACKGROUND: Immigration from regions with a high incidence of tuberculosis (TB)
      has slowed the decline of TB in low-incidence regions. Targeted screening of new
      immigrants and treatment for latent TB infection (LTBI) is needed to reinvigorate
      this decline. This meta-analysis compares LTBI diagnostic tests by positive test
      prevalence and proportion of positive tests by TB incidence. METHODS: A
      systematic literature search was performed and data extracted based on tuberculin
      skin test (TST) and/or interferon-gamma release assay (IGRA) use in immigrants.
      For the eight studies performing tests concurrently, data were compared by
      positive tests and concordance, while other studies comparing individual tests
      were analyzed based on demographic factors. Data were analyzed via meta-analysis.
      RESULTS: Forty-five studies with a combined sample size of 93,249 individuals
      were included in the analyses, 2206 of which were from the eight concurrent
      studies. Odds of a positive TST were significantly higher than an IGRA (odds
      ratio 1.46; 95% confidence interval 1.07-2.01) and test agreement was moderate.
      Proportion of positive TST and IGRA tests increased with TB incidence, although
      not linearly. CONCLUSION: TST and IGRA data relating to immigrants are lacking,
      especially long-term follow-up and comparative data. Further data are urgently
      needed to determine TB risks after immigration, long-term TB development, and
      treatment outcomes.

PMID- 25851741
TI  - The effect of sirolimus-based immunosuppression vs. conventional prophylaxis
      therapy on cytomegalovirus infection after liver transplantation.
AB  - OBJECTIVE: The aim of this study was to assess the efficacy of sirolimus-based
      immunosuppression vs. conventional prophylaxis therapy in preventing
      cytomegalovirus (CMV) infection or disease in liver transplantation recipients.
      METHODS: One hundred and twenty-seven consecutive liver transplant recipients,
      with a minimum of one-yr follow-up from 2008 to 2013 in the first affiliated
      hospital of Nanchang University, were retrospectively divided into the sirolimus
      treated (n = 51) and ganciclovir-treated (n = 76) groups. The CMV incidence,
      rejection events, and survival rate were compared. RESULTS: The overall
      incidences of CMV events were decreased but did not reach statistical
      significance in the sirolimus arm compared with the ganciclovir arm (p > 0.05) at
      one yr after liver transplantation. There was no significant difference in the
      rejection incidence and survival rates between the two groups. CONCLUSIONS:
      Sirolimus-based immunosuppression had a lower incidence of CMV infection compared
      with conventional prophylaxis therapy and did not increase rejection risks and
      mortality after liver transplantation, indicating that with the use of an
      mammalian target-of-rapamycin (mTOR)-inhibitor, CMV prophylaxis may be
      dispensable.

PMID- 25851742
TI  - Ocular motor measures of cognitive dysfunction in multiple sclerosis II: working
      memory.
AB  - Our companion paper documents pervasive inhibitory deficits in multiple sclerosis
      (MS) using ocular motor (OM) measures. Here we investigated the utility of an OM
      working memory (WMem) task in characterising WMem deficits in these patients as a
      function of disease status and disease duration. 22 patients with CIS, 22 early
      clinically definite MS patients (CDMS: <7 years of diagnosis), 22 late CDMS
      patients (>7 years from diagnosis), and 22 healthy controls participated. All
      participants completed the ocular motor WMem task, the paced auditory serial
      addition test (PASAT), and the symbol digit modalities test (SDMT). Clinical
      disability was characterised in CDMS patients using the Expanded Disability
      Severity Scale (EDSS). WMem performance was measured as proportion of errors
      (WMem errors), saccade latency, and relative sensitivity to WMem loading (WMem
      effect), an indicator of WMem capacity. All patient groups performed more WMem
      errors than controls with proportion of WMem errors, and degree of WMem effect
      increasing with increasing disease duration. A larger WMem effect, reflecting
      poorer WMem capacity, corresponded to poorer performance on neuropsychological
      measures, and a higher disability score for CDMS patients with the longest
      disease duration; an observation that suggests wider implication of WMem
      executive processes with advancing disease. Conspicuously, performance decrements
      on standard neuropsychological testing did not similarly increase commensurate
      with disease duration. The ocular motor WMem task appears to meaningfully
      dissociate WMem deficit from healthy individuals as well as a function of
      increasing disease duration. Potentially, this task represents a highly
      informative and objective method by which to ascertain progressive WMem changes
      from the earliest inception of MS.

PMID- 25851744
TI  - High-risk prostate cancer and radical prostatectomy in the setting and context of
      multidisciplinary care.

PMID- 25851743
TI  - Ocular motor measures of cognitive dysfunction in multiple sclerosis I:
      inhibitory control.
AB  - Our ability to control and inhibit behaviours that are inappropriate, unsafe, or
      no longer required is crucial for functioning successfully in complex
      environments. Here, we investigated whether a series of ocular motor (OM)
      inhibition tasks could dissociate deficits in patients with multiple sclerosis
      (MS), including patients with only a probable diagnosis (clinically isolated
      syndrome: CIS), from healthy individuals as well as a function of increasing
      disease duration. 25 patients with CIS, 25 early clinically definite MS patients
      (CDMS: <=7 years of diagnosis), 24 late CDMS patients (>7 years from diagnosis),
      and 25 healthy controls participated. All participants completed a series of
      classic OM inhibition tasks [antisaccade (AS) task, memory-guided (MG) task,
      endogenous cue task], and a neuropsychological inhibition task [paced auditory
      serial addition test (PASAT)]. Clinical disability was characterised in CDMS
      patients using the Expanded Disability Severity Scale (EDSS). OM (latency and
      error) and PASAT performance were compared between patient groups and controls,
      as well as a function of disease duration. For CDMS patients only, results were
      correlated with EDSS score. All patient groups made more errors than controls on
      all OM tasks; error rate did not increase with increasing disease duration. In
      contrast, saccade latency (MG and endogenous cue tasks) was found to worsen with
      increasing disease duration. PASAT performance did not discriminate patient
      groups or disease duration. The EDSS did not correlate with any measure. These OM
      measures appear to dissociate deficit between patients at different disease
      durations. This suggests their utility as a measure of progression from the
      earliest inception of the disease.

PMID- 25851745
TI  - Prevalence of gastrointestinal parasites in captive non-human primates of twenty
      four zoological gardens in China.
AB  - Captive primates are susceptible to gastrointestinal (GIT) parasitic infections,
      which are often zoonotic and can contribute to morbidity and mortality. Fecal
      samples were examined by the means of direct smear, fecal flotation, fecal
      sedimentation, and fecal cultures. Of 26.51% (317/1196) of the captive primates
      were diagnosed gastrointestinal parasitic infections. Trichuris spp. were the
      most predominant in the primates, while Entamoeba spp. were the most prevalent in
      Old World monkeys (P < 0.05). These preliminary data will improve the management
      of captive primates and the safety of animal keepers and visitors. 

PMID- 25851746
TI  - Copper oxide and zinc oxide nanomaterials act as inhibitors of multidrug
      resistance transport in sea urchin embryos: their role as chemosensitizers.
AB  - The ability of engineered nanomaterials (NMs) to act as inhibitors of ATP-binding
      cassette (ABC) efflux transporters in embryos of white sea urchin (Lytechinus
      pictus) was studied. Nanocopper oxide (nano-CuO), nanozinc oxide (nano-ZnO), and
      their corresponding metal ions (CuSO4 and ZnSO4) were used as target chemicals.
      The results showed that nano-CuO, nano-ZnO, CuSO4, and ZnSO4, even at relatively
      low concentrations (0.5 ppm), significantly increased calcein-AM (CAM, an
      indicator of ABC transporter activity) accumulation in sea urchin embryos at
      different stages of development. Exposure to nano-CuO, a very low solubility NM,
      at increasing times after fertilization (>30 min) decreased CAM accumulation, but
      nano-ZnO (much more soluble NM) did not, indicating that metal ions could cross
      the hardened fertilization envelope, but not undissolved metal oxide NMs.
      Moreover, nontoxic levels (0.5 ppm) of nano-CuO and nano-ZnO significantly
      increased developmental toxicity of vinblastine (an established ABC transporter
      substrate) and functioned as chemosensitizers. The multidrug resistance
      associated protein (MRP, one of ABC transporters) inhibitor MK571 significantly
      increased copper concentrations in embryos, indicating ABC transporters are
      important in maintaining low intracellular copper levels. We show that low
      concentrations of nano-CuO and nano-ZnO can make embryos more susceptible to
      other contaminants, representing a potent amplification of nanomaterial-related
      developmental toxicity. 

PMID- 25851747
TI  - Towards the resolution of a long-standing evolutionary question: muscle identity
      and attachments are mainly related to topological position and not to primordium
      or homeotic identity of digits.
AB  - Signaling for limb bone development usually precedes that for muscle development,
      such that cartilage is generally present before muscle formation. It remains
      obscure, however, if: (i) tetrapods share a general, predictable spatial
      correlation between bones and muscles; and, if that is the case, if (ii) such a
      correlation would reflect an obligatory association between the signaling
      involved in skeletal and muscle morphogenesis. We address these issues here by
      using the results of a multidisciplinary analysis of the appendicular muscles of
      all major tetrapod groups integrating dissections, muscle antibody stainings,
      regenerative and ontogenetic analyses of fluorescently-labeled (GFP) animals, and
      studies of non-pentadactyl human limbs related to birth defects. Our synthesis
      suggests that there is a consistent, surprising anatomical pattern in both normal
      and abnormal phenotypes, in which the identity and attachments of distal limb
      muscles are mainly related to the topological position, and not to the
      developmental primordium (anlage) or even the homeotic identity, of the digits to
      which they are attached. This synthesis is therefore a starting point towards the
      resolution of a centuries-old question raised by authors such as Owen about the
      specific associations between limb bones and muscles. This question has crucial
      implications for evolutionary and developmental biology, and for human medicine
      because non-pentadactyly is the most common birth defect in human limbs. In
      particular, this synthesis paves the way for future developmental experimental
      and mechanistic studies, which are needed to clarify the processes that may be
      involved in the elaboration of the anatomical patterns described here, and to
      specifically test the hypothesis that distal limb muscle identity/attachment is
      mainly related to digit topology. 

PMID- 25851748
TI  - Deviant early pregnancy maternal triglyceride levels and increased risk of
      congenital anomalies: a prospective community-based cohort study.
AB  - OBJECTIVE: The maternal lipid profile could be of importance in congenital
      anomaly development. This study therefore investigates whether the maternal lipid
      profile during early pregnancy is associated with major nonsyndromic congenital
      anomalies (MNCA). DESIGN: Prospective community-based cohort study. SETTING:
      Amsterdam Born Children and their Development (ABCD) study. POPULATION: A cohort
      of 3074 pregnant women recruited in 2003-2004 and their offspring. METHODS: Non
      fasting blood samples from pregnant women participating in the ABCD-study (median
      12.9 weeks of gestation) were analysed for triglycerides (TG), cholesterol (TC),
      free fatty acids (FFA), apolipoprotein B (ApoB), and apolipoprotein A1 (ApoA) (n
      = 3074). The perinatal outcome (MNCA) was obtained from the Youth Health Care
      Registration and two questionnaires. Adjustment was made for ethnicity. MAIN
      OUTCOME MEASURE: MNCA prevalence. RESULTS: The prevalence of MNCA was 2.2% (n =
      68: 20 cardiovascular, 25 bone and muscle, and 23 other single anomalies). A
      nonlinear association was found between maternal TG levels and MNCA prevalence.
      With a lower or higher level of maternal TG, the estimated probability increased:
      a TG level of 0.73 mmol/l (5th percentile), of 1.28 mmol/l (50th percentile), and
      of 2.35 mmol/l (95th percentile) corresponded with an estimated probability of
      3.6, 2.1, and 2.9%, respectively. Unadjusted subgroup analyses showed that the U
      shaped association was most prominent for cardiovascular congenital anomalies.
      Other lipids were not associated with MNCA. CONCLUSIONS: Both low and high
      maternal TG levels during early pregnancy were associated with an increased risk
      of MNCA in offspring. This suggests that an attempt should be made to normalise
      TG levels before or during early pregnancy; however, replication of our results
      is necessary before clinical practice recommendations can be made.

PMID- 25851749
TI  - A highly sensitive square wave voltammetry based biosensor for kinase activity
      measurements.
AB  - An electrochemical biosensor has been developed for ultrasensitive, label-free
      determination of protein kinase activity. The sensor is composed of a unique
      peptide monolayer on a gold electrode. It identifies the order change in the
      monolayer upon phosphorylation, via square wave voltametry (SWV) measurements.
      Disorder caused by the introduction of the phosphate groups onto the middle of
      the peptide sequence results in pinhole formation and therefore an increase in
      the electrochemical signal. The measured sensitivity was 100 nM of kinase and the
      dynamic range was 100 nM up to 11 MUM. Sensitivity was an order of magnitude
      higher, and the dynamic range wider by two orders of magnitude, as compared to
      our previously reported impedimetric method, in which the sensitivity was 1 MUM,
      and the dynamic range was 1-20 MUM.

PMID- 25851750
TI  - Serum antibody levels correlate with oral fungal cell numbers and influence the
      patients' response to chronic paracoccidioidomycosis.
AB  - Paracoccidioidomycosis (PCM) is a neglected fungal disease that elicits an
      important granulomatous inflammatory reaction which aims to isolate the fungi and
      resolve the infection; besides the innate cellular response, the patients' sera
      may contain different levels of antibodies directed against PCM's pathogenic
      agent: Paracoccidioides brasiliensis (Pb). The aim of the study was to assess the
      distinct serum antibody levels of 19 chronic PCM patients and to associate these
      levels to the granulomatous inflammatory response and presence of fungi in oral
      lesions caused by Pb. The presence of Pb was detected and counted within oral
      tissues using immunohistochemistry; antibody levels were classified as negative,
      low-grade, moderate or high-grade groups. The Kruskal-Wallis and Dunn's test were
      used to verify possible associations among the groups. Interestingly, lower
      antibody titres were associated with lesser numbers of Pb, which favours the
      cellular response over the humoral response to fight PCM. On the other hand,
      negative serological results were linked to a higher presence of Pb in the
      tissues, indicating that a deficient humoral response supports the fungal
      proliferation. The number of Pb was conveniently associated with the level of
      serum antibodies, showing that the humoral immune response is required, however,
      not solely responsible to restrain the dissemination of Pb. 

PMID- 25851751
TI  - Vortioxetine, a multimodal antidepressant for generalized anxiety disorder: a
      systematic review and meta-analysis.
AB  - Vortioxetine has a beneficial pharmacological profile for reducing anxiety and
      depression. Recently, a number of randomized, double-blind, placebo-controlled
      clinical trials (RCTs) of vortioxetine have been conducted in patients with
      generalized anxiety disorder (GAD); however, the results from GAD RCTs are
      inconsistent. With an extensive search of databases and clinical trial
      registries, four published short-term RCTs were identified and included in the
      present meta-analysis. The mean change in total scores on the Hamilton Anxiety
      Rating Scale (HAMA) from baseline was the primary endpoint. The secondary
      endpoints included the response and remission rates, as defined by a >=50%
      reduction in HAMA total scores and a <=7 change in the HAMA total score at the
      end of treatment. In addition, the mean change in the HAMA total score from
      baseline in the subgroup with a HAMA total score >=25 at baseline was included.
      Vortioxetine was significantly more effective than was placebo, with a
      standardized mean difference (SMD) of -0.118 (95% CIs, -0.203 to -0.033, P =
      0.007). In particular, those with severe GAD (HAMA total score >=25 at baseline)
      had a significantly greater benefit from vortioxetine than those without (SMD = 
      0.338, 95% CIs = -0.552 to -0.124, p = 0.002). The odds ratios (ORs) for
      vortioxetine for response and remission were 1.221 (95% CIs, 1.027 to 1.452, P =
      0.024) and 1.052 (95% CIs, 0.853 to 1.296, P = 0.637), respectively.
      Discontinuation due to adverse events (AEs) (OR = 1.560, 1.006 to 2.419, p =
      0.047) was marginally higher in vortioxetine than placebo treatment, whereas
      discontinuation due to any reason (OR = 0.971, 0.794 to 1.187, p = 0.771) and
      inefficacy (OR = 0.687, 0.380 to 1.243, p = 0.215) were not significantly
      different among treatment groups. Although our results suggest that vortioxetine
      may have a potential as an another treatment option for GAD (especially for
      severe GAD), they should be interpreted and translated into clinical practice
      with caution, as the meta-analysis was based on a limited number of RCTs. 

PMID- 25851752
TI  - Interstitial granulomatous dermatitis due to borreliosis.

PMID- 25851753
TI  - Acquired linear Becker's nevus on lower limb in blaschkoid pattern.

PMID- 25851755
TI  - Clinical and dermoscopic features of eccrine poroma.

PMID- 25851754
TI  - Novel transglutaminase 1 mutations in a Chinese patient with severe lamellar
      ichthyosis phenotype.

PMID- 25851756
TI  - Weekly azathioprine pulse versus daily azathioprine in the treatment of
      Parthenium dermatitis: A non-inferiority randomized controlled study.
AB  - BACKGROUND: Azathioprine in daily doses has been shown to be effective and safe
      in the treatment of Parthenium dermatitis. Weekly pulses of azathioprine (WAP)
      are also effective, but there are no reports comparing the effectiveness and
      safety of these two regimens in this condition. AIMS: To study the efficacy and
      safety of WAP and daily azathioprine in Parthenium dermatitis. METHODS: Sixty
      patients with Parthenium dermatitis were randomly assigned to treatment with
      azathioprine 300 mg weekly pulse or azathioprine 100 mg daily for 6 months.
      Patients were evaluated every month to assess the response to treatment and side
      effects. RESULTS: The study included 32 patients in the weekly azathioprine group
      and 28 in the daily azathioprine group, of whom 25 and 22 patients respectively
      completed the study. Twenty-three (92%) patients on WAP and 21 (96%) on daily
      azathioprine had a good or excellent response. The mean pretreatment clinical
      severity score decreased from 26.4+/-14.5 to 4.7+/-5.1 in the WAP group, and from
      36.1+/-18.1 to 5.7+/-6.0 in the daily azathioprine group, which was statistically
      significant and comparable (P=0.366). Patients on WAP had a higher incidence of
      adverse effects (P=0.02). LIMITATIONS: The study had a small sample size and the
      amount of clobetasol propionate used in each patient was not determined, though
      it may not have affected the study outcome due to its comparable use in both
      groups. CONCLUSIONS: Azathioprine 300 mg weekly pulse and 100 mg daily dose are
      equally effective and safe in the treatment of Parthenium dermatitis.

PMID- 25851757
TI  - Histopathological evidence of efficacy of microneedle radiofrequency for
      treatment of axillary hyperhidrosis.

PMID- 25851758
TI  - Progressive cribriform and zosteriform hyperpigmentation.

PMID- 25851759
TI  - Bullous eosinophilic cellulitis with subcorneal pustules.

PMID- 25851760
TI  - Leser-Trelat sign with primary hepatic carcinoma.

PMID- 25851761
TI  - Evaluation of the effect of Block Level Awareness Campaign on performance
      indicators of National Leprosy Elimination Program in Vadodara district, Gujarat,
      India.
AB  - BACKGROUND: Leprosy is probably the oldest disease afflicting mankind and a
      public health problem for centuries. Many cases are hidden or undiagnosed,
      especially due to social stigma, and neglect of painless patches. Between years
      2001 and 2005, during which time active surveillance for detection of leprosy was
      in practice, a steep fall in the prevalence rate (PR) of leprosy was observed.
      However, during later years, leprosy program discontinued active surveillance for
      detection of leprosy cases. Presently block level awareness campaign (BLAC) is a
      special measure undertaken in a campaign mode during September-November in
      priority areas, (PR>1/10000 population), during which information, education and
      communication (IEC) activities and active surveillance of leprosy cases is done.
      AIMS: To evaluate the effect of Block Level Awareness Campaign on performance
      indicators of national leprosy elimination program (NLEP) in Vadodara district.
      METHODS: The campaign was carried out for 6 days in 12 talukas of Vadodara
      district by the district leprosy office, Vadodara. Trained teams of health
      workers carried out information, education and communication (IEC) activity and
      active surveillance by undertaking house to house survey in each primary health
      centre (PHC) area. Suspected cases were identified by the team and confirmed
      clinically by medical officers in the primary health centre of the corresponding
      areas. A district nucleus team (DNT) validated these confirmed cases. These data
      were compared with the district's national leprosy eradication programme (NLEP)
      data for the same year, 2012 and the previous year, 2011. RESULTS: A total of
      1,574,586 persons, comprising 76%of the population surveyed, were screened for
      leprosy, which resulted in detection of 358 clinically confirmed new cases of
      leprosy, out of which 225 (62.8%) were paucibacillary (PB) and 133 (37.2%) were
      multibacillary (MB) leprosy. Of these cases, 14 (4%) had deformities, and 37
      (10.3%) were children. LIMITATIONS: Only 76% of the population could be covered.
      Histopathological confirmation of the diagnosis was not undertaken. Because of
      the large number of health workers invovled, variations in their skills may have
      influenced the diagnosis of suspected cases. CONCLUSIONS: Active surveillance
      linked to focused block level campaigns can be useful tools to detect new hidden
      leprosy cases.

PMID- 25851762
TI  - Pemphigus vulgaris localised exclusively to the penis.

PMID- 25851763
TI  - Clinical and histological patterns of dermatofibroma without gross skin surface
      change: A comparative study with conventional dermatofibroma.
AB  - BACKGROUND: Dermatofibroma sometimes clinically presents as a nodular lesion
      without gross skin surface change. Clinicopathologic features of this variant of
      dermatofibroma have not been evaluated. AIMS: To assess clinicopathologic
      features of dermatofibroma presenting as a subcutaneous nodule. METHODS: This
      study reviewed the clinical and histological features of 42 cases of subcutaneous
      dermatofibromas and compared them with 95 cases of conventional dermatofibroma.
      RESULTS: Dermatofibroma without gross skin surface change was associated with a
      shorter pre-diagnosis duration than conventional dermatofibroma. Increase in size
      during the pre-diagnosis period was significantly more frequent in the
      conventional type. In addition, these dermatofibromas were more likely than the
      conventional type to occur in the head and neck region. Although tumor depth was
      deeper than in the conventional type, less than half of the dermatofibromas
      without gross skin surface change were found histologically to be "subcutaneous"
      or "deep-penetrating dermatofibroma". Subcutaneous extension was more frequent in
      these dermatofibromas while focal stromal hyalinization and hemosiderin deposits
      were more common in the conventional type. LIMITATIONS: This study is a
      retrospective, single center design. CONCLUSION: The present study suggests that
      dermatofibroma without gross skin surface change is a variant type with distinct
      clinical and histological features that distinguish them from conventional
      dermatofibroma.

PMID- 25851764
TI  - Onychomycosis: A study of self-recognition by patients and quality of life.
AB  - BACKGROUND: Onychomycosis accounts for approximately half of all nail disorders
      and is usually asymptomatic. OBJECTIVES: To evaluate patients' recognition of
      fungal nail disease, concomitant fungal skin diseases, complications, and quality
      of life. METHODS: Patients from the fungal nail clinic were enrolled between May
      2011 and April 2012. Patients' awareness of diseased nails was evaluated and the
      Dermatology Life Quality Index (DLQI) questionnaire was used to evaluate the
      impact of dermatologic disease on quality of life. RESULTS: A total of 110
      patients with onychomycosis were enrolled in the study, of which 64 (58.2%) were
      female and the mean age was  60.8 years. The number of patients who were able to
      recognize the presence of onychomycosis was 71 (64.5%), while 32 (29.1%) and 7
      (6.4%) were diagnosed by a dermatologist and other physicians, respectively.
      Multivariate analysis showed that patient recognition of the disease was
      significantly associated with female sex and young age. The mean DLQI score was 
      3.6. LIMITATION: Patient recall bias including the duration of fungal nail
      infection, long-term past history and previous treatment was a limitation of this
      study that affected DLQI scores. CONCLUSION: About half of onychomycosis
      patients, especially elderly males, could not recognize the disease by
      themselves. It is important for physicians to educate patients with risk factors
      for onychomycosis to recognize this condition early to prevent concomitant
      infection and complications, and to improve patients' well-being.

PMID- 25851765
TI  - Chalazion clamp in dermatology revisited.

PMID- 25851766
TI  - Type of anesthesia and differences in clinical outcome after intra-arterial
      treatment for ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Intra-arterial treatment (IAT) in patients with acute
      ischemic stroke (AIS) can be performed with or without general anesthesia (GA).
      Previous studies suggested that IAT without the use of GA (non-GA) is associated
      with better clinical outcome. Nevertheless, no consensus exists about the
      anesthetic management during IAT of AIS patients. This study investigates the
      association between type of anesthesia and clinical outcome in a large cohort of
      patients with AIS treated with IAT. METHODS: All consecutive patients with AIS of
      the anterior circulation who received IAT between 2002 and 2013 in 16 Dutch
      hospitals were included in the study. Primary outcome was functional outcome on
      the modified Rankin Scale at discharge. Difference in primary outcome between GA
      and non-GA was estimated using multiple ordinal regression analysis, adjusting
      for age, stroke severity, occlusion of the internal carotid artery terminus,
      previous stroke, atrial fibrillation, and diabetes mellitus. RESULTS: Three
      hundred forty-eight patients were included in the analysis; 70 patients received
      GA and 278 patients did not receive GA. Non-GA was significantly associated with
      good clinical outcome (odds ratio 2.1, 95% confidence interval 1.02-4.31). After
      adjusting for prespecified prognostic factors, the point estimate remained
      similar; statistical significance, however, was lost (odds ratio 1.9, 95%
      confidence interval 0.89-4.24). CONCLUSIONS: Our study suggests that patients
      with AIS of the anterior circulation undergoing IAT without GA have a higher
      probability of good clinical outcome compared with patients treated with general
      anesthesia.

PMID- 25851768
TI  - Endovascular treatment for ischemic strokes with large vessel occlusion: proven
      therapy and bright future.

PMID- 25851767
TI  - Hospital costs associated with atrial fibrillation for patients with ischemic
      stroke aged 18-64 years in the United States.
AB  - BACKGROUND AND PURPOSE: Hospital costs associated with atrial fibrillation (AFib)
      among patients with stroke have not been well-studied, especially among people
      aged <65 years. We estimated the AFib-associated hospital costs in US patients
      aged 18 to 64 years. METHODS: We identified hospital admissions with a primary
      diagnosis of ischemic stroke from the 2010 to 2012 MarketScan Commercial Claims
      and Encounters inpatient data sets, excluding those with capitated health
      insurance plans, aged <18 or >64 years, missing geographic region, hospital costs
      below the 1st or above 99th percentile, and having carotid intervention (n=40
      082). We searched the data for AFib and analyzed the costs for nonrepeat and
      repeat stroke admissions separately. We estimated the AFib-associated costs using
      multivariate regression models controlling for age, sex, geographic region, and
      Charlson comorbidity index. RESULTS: Of the 33 500 nonrepeat stroke admissions,
      2407 (7.2%) had AFib. Admissions with AFib cost $4991 more than those without
      AFib ($23 770 versus $18 779). For the 6582 repeat stroke admissions, 397 (6.0%)
      had AFib. The costs were $3260 more for those with AFib than those without ($24
      119 versus $20 929). After controlling for potential confounders, AFib-associated
      costs for nonrepeat stroke admissions were $4905, representing 20.6% of the total
      costs for the admissions. Both the hospital costs and the AFib-associated costs
      were associated with age, but not with sex. AFib-associated costs for repeat
      stroke admissions were not significantly higher than for non-AFib patients,
      except for those aged 55 to 64 years ($3537). CONCLUSIONS: AFib increased the
      hospital cost of ischemic stroke substantially. Further investigation on AFib
      associated costs for repeat stroke admissions is needed.

PMID- 25851769
TI  - Prognostications of fibrillations.

PMID- 25851770
TI  - Delayed Administration of Tat-HA-NR2B9c Promotes Recovery After Stroke in Rats.
AB  - BACKGROUND AND PURPOSE: Previous studies reported that Tat-NR2B9c, a peptide
      disrupting the N-methyl-d-aspartate receptor-postsynaptic density protein-95
      interaction, reduced ischemic damage in the acute phase after stroke. However,
      its effect in the subacute phase is unknown. The aim of this study is to
      determine whether disrupting the N-methyl-d-aspartate receptor-postsynaptic
      density protein-95 interaction in the subacute phase promotes recovery after
      stroke. METHODS: Studies were performed on Sprague-Dawley rats or nNOS(-/-) mice,
      and experimental ischemic stroke was induced by middle cerebral artery occlusion.
      Animals were treated with drugs starting at day 4 after ischemia. Sensorimotor
      functions and spatial learning and memory ability were assessed after drug
      treatment. Then, rats were euthanized for morphological observation and
      biochemical tests. RESULTS: Disrupting the N-methyl-d-aspartate receptor
      postsynaptic density protein-95 interaction with Tat-HA-NR2B9c significantly
      ameliorated the ischemia-induced impairments of spatial memory and sensorimotor
      functions in rats during subacute stage but did not improve stroke outcome in
      nNOS(-/-) mice. Consistent with the functional recovery, Tat-HA-NR2B9c
      substantially increased neurogenesis in the dentate gyrus and dendritic spine
      density of mature neurons in the motor cortex of rats, meanwhile, reversed the
      ischemia-induced formation of S-nitrosylation-cyclin-dependent kinase 5 and
      increased cyclin-dependent kinase 5 activity in ipsilateral hippocampus. However,
      directly blocking N-methyl-d-aspartate receptors with MK-801 or Ro 25-6981 did
      not show the beneficial effects above. CONCLUSIONS: Dissociating N-methyl-d
      aspartate receptor-postsynaptic density protein-95 coupling by Tat-HA-NR2B9c in
      the subacute phase after stroke promotes functional recovery, probably because of
      that it increases neurogenesis and dendritic spine density of mature neurons via
      regulating cyclin-dependent kinase 5 in the ischemic brain.

PMID- 25851771
TI  - Predictors of finding occult atrial fibrillation after cryptogenic stroke.
AB  - BACKGROUND AND PURPOSE: Occult paroxysmal atrial fibrillation (AF) is found in a
      substantial minority of patients with cryptogenic stroke. Identifying reliable
      predictors of paroxysmal AF after cryptogenic stroke would allow clinicians to
      more effectively use outpatient cardiac monitoring and ultimately reduce
      secondary stroke burden. METHODS: We analyzed a retrospective cohort of
      consecutive patients who underwent 28-day mobile cardiac outpatient telemetry
      after cryptogenic stroke or transient ischemic stroke. Univariate and
      multivariable analyses were performed to identify clinical, echocardiographic,
      and radiographic features associated with the detection of paroxysmal AF.
      RESULTS: Of 227 patients with cryptogenic stroke (179) or transient ischemic
      stroke (48), 14% (95% confidence interval, 9%-18%) had AF detected on mobile
      cardiac outpatient telemetry, 58% of which was >=30 seconds in duration. Age >60
      years (odds ratio, 3.7; 95% confidence interval, 1.3-11) and prior cortical or
      cerebellar infarction seen on neuroimaging (odds ratio, 3.0; 95% confidence
      interval, 1.2-7.6) were independent predictors of AF. AF was detected in 33% of
      patients with both factors, but only 4% of patients with neither. No other
      clinical features (including demographics, CHA2DS2-VASc [combined stroke risk
      score: congestive heart failure, hypertension, age, diabetes, prior
      stroke/transient ischemic attack, vascular disease, sex] score, or stroke
      symptoms), echocardiographic findings (including left atrial size or ejection
      fraction), or radiographic characteristics of the acute infarction (including
      location, topology, or number) were associated with AF detection. CONCLUSIONS:
      Mobile cardiac outpatient telemetry detects AF in a substantial proportion of
      cryptogenic stroke patients. Age >60 years and radiographic evidence of prior
      cortical or cerebellar infarction are robust indicators of occult AF. Patients
      with neither had a low prevalence of AF.

PMID- 25851772
TI  - Time trends in incidence and case fatality of ischemic stroke: the tromso study
      1977-2010.
AB  - BACKGROUND AND PURPOSE: Ischemic stroke incidence has declined in industrialized
      countries the last decades, with possible exception for the youngest age groups.
      We estimated age- and sex-specific trends in incidence and case fatality of first
      ever ischemic stroke between 1977 and 2010 in a Norwegian municipality. METHODS:
      Age-adjusted time trends in incidence from 1977 to 2010 were estimated by
      fractional polynomial and Poisson regression, and case fatality by logistic
      regression in 36 575 participants of the population-based Tromso Study. RESULTS:
      There were 1214 first-ever ischemic strokes within a total follow-up time of 611
      176 person-years. The overall age- and sex-adjusted incidence decreased by 24% in
      1995 to 2010. In women aged 30 to 49 years, the incidence increased significantly
      from 1980 to 2010. In men aged 30 to 49 years, there was a nonsignificant, rising
      trend from 1977 to 2010. Men aged 50 to 64 years had similar incidence in 2010
      compared with 1989. From the mid-1990s to 2010, the incidence declined
      significantly in women aged 50 to 74 years and in men aged 65 to 74 years, but
      remained stable in those aged >=75 years. Case fatality decreased significantly
      in men aged 30 to 84 years from 1995 to 2010, whereas there was no significant
      change in women. CONCLUSIONS: Age-adjusted incidence of first-ever ischemic
      stroke increased in young women, declined in women aged 50 to 74 years and men
      aged 65 to 74 years and remained stable among the oldest. Case fatality declined
      in men aged 30 to 84 years, but not in women.

PMID- 25851773
TI  - Left phrenic nerve anatomy relative to the coronary venous system: Implications
      for phrenic nerve stimulation during cardiac resynchronization therapy.
AB  - The objective of this study was to quantitatively characterize anatomy of the
      human phrenic nerve in relation to the coronary venous system, to reduce
      undesired phrenic nerve stimulation during left-sided lead implantations. We
      obtained CT scans while injecting contrast into coronary veins of 15 perfusion
      fixed human heart-lung blocs. A radiopaque wire was glued to the phrenic nerve
      under CT, then we created three-dimensional models of anatomy and measured
      anatomical parameters. The left phrenic nerve typically coursed over the basal
      region of the anterior interventricular vein, mid region of left marginal veins,
      and apical region of inferior and middle cardiac veins. There was large variation
      associated with the average angle between nerve and veins. Average angle across
      all coronary sinus tributaries was fairly consistent (101.3 degrees -111.1
      degrees ). The phrenic nerve coursed closest to the middle cardiac vein and left
      marginal veins. The phrenic nerve overlapped a left marginal vein in >50% of
      specimens.

PMID- 25851774
TI  - Red meat intolerance in patients submitted to gastric bypass: a 4-year follow-up
      study.
AB  - BACKGROUND: Bariatric surgery provides significant weight reduction; however, it
      may result in food intolerance followed by gastrointestinal complications that
      may lead to nutritional deficiencies. This study evaluated the influence of red
      meat intolerance on the dietary pattern, biochemical indicators, and clinical
      symptoms after Roux-en-Y gastric bypass (RYGB). METHODS: This retrospective study
      evaluated patients 4 years after RYGB. The patients were divided into 2 groups:
      patients with and without red meat intolerance, and data for the following were
      collected: food intake, anthropometric data, biochemical data, and presence of
      nausea, vomiting, weakness, weak nails, and hair loss. The difference between
      groups in the times postoperative was determined by ANOVA. RESULTS: Of the 72
      patients included in the study, 63 were evaluated during the first postoperative
      year, 45 during the second, 56 during the third, and 41 during the fourth. Red
      meat intolerance was observed in 49.2%, 42.2%, 46.4%, and 39% of the patients
      after 1, 2, 3, and 4 years, respectively. After 1 year, the intolerant group
      showed lower calorie, carbohydrate, and iron intake. After 3 years, tolerant
      patients showed weight regain (2.9 +/- 5.3 kg), while the intolerant ones
      remained stable. There was no difference in the presence of clinical symptoms or
      biochemical indicators between groups. CONCLUSION: Red meat intolerance is
      frequent after bariatric surgery and may alter energy, iron intake, and weight
      loss; however, it is not associated with the presence of clinical symptoms and
      biochemical profile.

PMID- 25851775
TI  - Comparison of the incidence of cholelithiasis after sleeve gastrectomy and Roux
      en-Y gastric bypass in obese patients: a prospective study.
AB  - BACKGROUND: Although the risk of cholelithiasis (CL) increases in patients after
      Roux-en-Y gastric bypass (RYGB), no prospective study has yet assessed the
      incidence of CL after sleeve gastrectomy (SG). OBJECTIVES: To compare,
      prospectively, the incidence and predictive factors for CL after both procedures.
      METHODS: A postoperative abdominal ultrasound follow-up was proposed to all
      patients with an intact gallbladder and who underwent RYGB or SG in Hopital Louis
      Mourier from 2008 onward. RESULTS: At least one ultrasound was performed on one
      hundred and sixty patients between 6 and 12 months postsurgery, 43 after SG and
      117 after RYGB. Age, gender, initial body-mass index, co-morbidities were similar
      in both groups. Weight loss (WL) at 6 months was significantly lower after SG
      than after RYGB (26.9 +/- 9.2 and 31.3 +/- 7.5 kg, respectively = .001). The
      incidences of CL after SG and RYGB were similar (28% versus 34% respectively, P =
      .57). Most cases of CL occurred in the first year post surgery. During the follow
      up, 12% and 13% of patients who underwent SG and RYGB, respectively, became
      symptomatic. WL of>30 kg at 6 months was a risk factor for CL after bariatric
      surgery, but we did not find any preoperative predictive factor for gallstone
      formation. CONCLUSIONS: Despite lower WL after SG, the incidence of CL after SG
      and RYGB was similar at 2 years. Our results suggest that rapid WL is the main
      element leading to gallstone formation after both procedures.

PMID- 25851776
TI  - Does perioperative nutrition and oral carbohydrate load sustainably preserve
      muscle mass after bariatric surgery? A randomized control trial.
AB  - BACKGROUND: Perioperative nutrition and preoperative oral carbohydrate loading
      (CHL) have a beneficial impact on the outcomes of gastrointestinal oncological
      surgery. However no data exists on their effect on morbidly obese patients.
      OBJECTIVES: Our aim was to establish the short-term and long-term impact of these
      modalities, notably on metabolically active lean body mass (LBM) - an important
      factor in maintaining long-term weight loss. METHODS: Patients undergoing
      laparoscopic Roux-en-Y gastric bypass were randomized to standard management or
      intervention: CHL drinks consumed 12 and 2 hours presurgery, and immediate
      postoperative peripheral parenteral nutrition. The primary outcome measured was
      LBM, measured by Bioelectrical Impedance Analysis (BIA), one and 12 months
      postsurgery. Secondary outcomes included excess weight loss (EBWL), 30-day
      complication rate, and length of stay. RESULTS: Of the 203 randomized patients,
      198 were included in the analysis. All 101 patients in the control group
      completed the one-year follow up and 76 completed the BIA. In the intervention
      group, 93 of 97 patients completed the one-year follow-up and 71 completed the
      BIA. At one and 12 months follow-up, body composition, LBM, or EBWL were
      comparable. There was no difference in operative outcomes, complications rates,
      or length of stay. There was no adverse effect in the intervention group.
      CONCLUSIONS: In a highly homogeneous group of morbidly obese patients with one
      year follow-up, CHL and short-term parenteral nutrition did not lead to
      significant or sustained LBM preservation or modification in EBWL. There was no
      significant decrease in complications or length of stay. Our study confirms the
      safety of these interventions, even in previously unstudied Type 2 diabetic
      patients.

PMID- 25851778
TI  - Effects of cytomegalovirus infection in human neural precursor cells depend on
      their differentiation state.
AB  - Cytomegalovirus (CMV) is the most common cause of congenital infection in
      developed countries and a major cause of neurological disability in children.
      Although CMV can affect multiple organs, the most important sequelae of
      intrauterine infection are related to lesions of the central nervous system.
      However, little is known about the pathogenesis and the cellular events
      responsible for neuronal damage in infants with congenital infection. Some
      studies have demonstrated that neural precursor cells (NPCs) show the greatest
      susceptibility to CMV infection in the developing brain. We sought to establish
      an in vitro model of CMV infection of the developing brain in order to analyze
      the cellular events associated with invasion by this virus. To this end, we
      employed two cell lines as a permanent source of NPC, avoiding the continuous use
      of human fetal tissue, the human SK-N-MC neuroblastoma cell line, and an
      immortalized cell line of human fetal neural origin, hNS-1. We also investigated
      the effect of the differentiation stage in relation to the susceptibility of
      these cell lines by comparing the neuroblastoma cell line with the multipotent
      cell line hNS-1. We found that the effects of the virus were more severe in the
      neuroblastoma cell line. Additionally, we induced hNS-1 to differentiate and
      evaluated the effect of CMV in these differentiated cells. Like SK-N-MC cells,
      hNS-1-differentiated cells were also susceptible to infection. Viability of
      differentiated hNS-1 cells decreased after CMV infection in contrast to
      undifferentiated cells. In addition, differentiated hNS-1 cells showed an
      extensive cytopathic effect whereas the effect was scarce in undifferentiated
      cells. We describe some of the effects of CMV in neural stem cells, and our
      observations suggest that the degree of differentiation is important in the
      acquisition of susceptibility. 

PMID- 25851777
TI  - Hypoalbuminemia is disproportionately associated with adverse outcomes in obese
      elective surgical patients.
AB  - BACKGROUND: Protein deficiency (PD) is a known risk factor for surgical
      complications; however, the risks of PD by weight class have not been well
      described. It was hypothesized that the combination of obesity and PD is
      associated with increased surgical complications compared with normal weight and
      normoalbuminemic patients. METHODS: A total of 85,833 general surgery patients
      undergoing elective operations within the 2011 National Surgical Quality
      Improvement Program were analyzed. Patients with conditions that could
      potentially confound serum albumin (SA) were excluded. Patients were stratified
      by normal (>3.0 g/dL) versus low (<3.0 g/dL) SA. The relative impact of SA and
      body mass index (BMI) (as individual and as combined variables) on surgical
      morbidity and mortality were assessed. Multivariate analyses were performed to
      identify independent risk factors for morbidity and mortality. RESULTS: Overall,
      2,088 (2.43%) patients had low preoperative SA. 587 (28.1%) patients with low
      preoperative SA were obese (BMI>30), versus 39,299 (46.9%) with normal
      preoperative SA. Importantly, the interaction of hypoalbuminemia and BMI was
      independently associated with all complications among hypoalbuminemic patients
      with BMI>40, and mortality for patients with BMI>30 after controlling for
      appropriate demographic characteristics, co-morbidities, surgical wound
      classification, operation type, and complexity (c-statistic: .803 and .874
      respectively). CONCLUSION: PD and obesity appear to synergistically increase the
      risk of surgical complications. Paradoxically, malnutrition may be less easily
      recognized in obese individuals and surgeons may need to more carefully evaluate
      this population before surgery. Future studies should investigate therapy to
      correct PD specifically among obese patients before surgery.

PMID- 25851779
TI  - Adult-onset subacute sclerosing panencephalitis manifesting as slowly progressive
      dementia.

PMID- 25851780
TI  - Class III PI3K-mediated prolonged activation of autophagy plays a critical role
      in the transition of cardiac hypertrophy to heart failure.
AB  - Pathological cardiac hypertrophy often leads to heart failure. Activation of
      autophagy has been shown in pathological hypertrophic hearts. Autophagy is
      regulated positively by Class III phosphoinositide 3-kinase (PI3K). However, it
      is unknown whether Class III PI3K plays a role in the transition of cardiac
      hypertrophy to heart failure. To address this question, we employed a previously
      established cardiac hypertrophy model in heat shock protein 27 transgenic mice
      which shares common features with several types of human cardiomyopathy. Age
      matched wild-type mice served as control. Firstly, a prolonged activation of
      autophagy, as reflected by autophagosome accumulation, increased LC3 conversion
      and decreased p62 protein levels, was detected in hypertrophic hearts from
      adaptive stage to maladaptive stage. Moreover, morphological abnormalities in
      myofilaments and mitochondria were presented in the areas accumulated with
      autophagosomes. Secondly, activation of Class III PI3K Vacuolar protein sorting
      34 (Vps34), as demonstrated by upregulation of Vps34 expression, increased
      interaction of Vps34 with Beclin-1, and deceased Bcl-2 expression, was
      demonstrated in hypertrophic hearts from adaptive stage to maladaptive stage.
      Finally, administration with Wortmaninn, a widely used autophagy inhibitor by
      suppressing Class III PI3K activity, significantly decreased autophagy activity,
      improved morphologies of intracellular apartments, and most importantly,
      prevented progressive cardiac dysfunction in hypertrophic hearts. Collectively,
      we demonstrated that Class III PI3K plays a central role in the transition of
      cardiac hypertrophy to heart failure via a prolonged activation of autophagy in
      current study. Class III PI3K may serve as a potential target for the treatment
      and management of maladaptive cardiac hypertrophy. 

PMID- 25851782
TI  - Poly(alpha-Peptoid)s Revisited: Synthesis, Properties, and Use as Biomaterial.
AB  - Polypeptoids have been of great interest in the polymer science community since
      the early half of the last century; however, they had been basically forgotten
      materials until the last decades in which they have enjoyed an exciting revival.
      In this mini-review, we focus on the recent developments in polypeptoid
      chemistry, with particular focus on polymers synthesized by the ring-opening
      polymerization (ROP) of amino acid N-carboxyanhydrides (NCAs). Specifically, we
      will review traditional monomer synthesis (such as Leuchs, Katchalski, and
      Kricheldorf) and recent advances in polymerization methods to yield both linear,
      cyclic, and functional polymers, solution and bulk thermal properties, and
      preliminary results on the use of polypeptoids as biomaterials (i.e
      immunogenicity, biodistribution, degradability, and drug delivery). 

PMID- 25851781
TI  - Serum levels of apolipoprotein A-I and high-density lipoprotein can predict organ
      failure in acute pancreatitis.
AB  - INTRODUCTION: Predicting severity of pancreatitis is an important goal.
      Clinicians are still searching for novel and simple biomarkers that can better
      predict persistent organ failure (OF). Lipoproteins, especially high-density
      lipoprotein (HDL), and apolipoprotein A-I (APO A-I), have been shown to have anti
      inflammation effects in various clinical settings. Severe acute pancreatitis
      (SAP) is associated with hypo-lipoproteinemia. We studied whether the
      concentrations of HDL and APO A-I can predict persistent OF in patients with
      predicted SAP admitted to the ICU. METHODS: In 66 patients with predicted SAP, we
      prospectively evaluated the relationship between lipid levels, inflammatory
      cytokines and clinical outcomes, including persistent OF and hospital mortality.
      Blood samples were obtained within 24 hours of admission to the ICU. RESULTS: HDL
      and APO A-I levels were inversely correlated with various disease severity
      scores. Patients with persistent OF had lower levels of HDL and APO A-I, while
      those with transient OF had lower levels of interleukin-6, tumor necrosis factor
      alpha and lower rates of hospital mortality. Meanwhile, hospital non-survivors
      had lower concentrations of HDL, and APO A-I compared to the survivors. By using
      the area under the receiver operating characteristic (AUROC) curve, both HDL and
      APO A-I demonstrated an excellent discriminative power for predicting persistent
      OF among all patients (AUROC 0.912 and 0.898 respectively) and among those with
      OF (AUROC 0.904 and 0.895 respectively). Pair-wise comparison of AUROC showed
      that both HDL and APO A-I had better discriminative power than C-reactive protein
      to predict persistent OF. CONCLUSIONS: Serum levels of HDL and APO A-I at
      admission to the ICU are inversely correlated with disease severity in patients
      with predicted SAP and can predict persistent OF in this clinical setting.

PMID- 25851783
TI  - The unprecedented recurrent diploid/tetraploid mosaicism of trisomy-18
      (mixoploidy; 4n+18/2n+18): clinical report.
AB  - We report on a 32-year-old woman who presented at gestational age of 14 weeks.
      During ultrasonographic examination, we discovered that her fetus had several
      important abnormalities, including a cystic hygroma, craniofacial defects (low
      set ears, broad nose), heart defects (single atrium, single ventricle), agenesis
      of corpus callosum, limb defects (clenched hands, pes equinovarus). Chorionic
      villus sampling and karyotyping revealed diploid/tetraploid mosaicism with
      trisomy 18 (mixoploidy; 4n+18/2n+18). Her second pregnancy was terminated because
      of the same clinical manifestations 1 year prior. Her first pregnancy resulted in
      the birth of an entirely healthy boy. As far as know, no other similar case has
      been presented in the literature.

PMID- 25851784
TI  - Evaluating Ketoreductase Exchanges as a Means of Rationally Altering Polyketide
      Stereochemistry.
AB  - Modular polyketide synthases (PKSs) are multidomain multienzymes responsible for
      the biosynthesis in bacteria of a wide range of polyketide secondary metabolites
      of clinical value. The stereochemistry of these molecules is an attractive target
      for genetic engineering in attempts to produce analogues exhibiting novel
      therapeutic properties. The exchange of ketoreductase (KR) domains in model PKSs
      has been shown in several cases to predictably alter the configuration of the
      beta-hydroxy functionalities but not of the alpha-methyl groups. By systematic
      screening of a broad panel of KR domains, we have identified two donor KRs that
      afford modification of alpha-methyl group stereochemistry. To the best of our
      knowledge, this provides the first direct in vivo evidence of KR-catalyzed
      epimerization. However, none of the introduced KRs afforded simultaneous
      alteration of methyl and hydroxy configurations in high yield. Therefore,
      swapping of whole modules might be necessary to achieve such changes in
      stereochemistry. 

PMID- 25851786
TI  - Rosette-forming glioneuronal tumour in a patient with multiple sclerosis.

PMID- 25851787
TI  - Systemic, cerebral, and pulmonary segmental mediolytc arteriopathy: Villainous
      masqueraders of vasculitis.
AB  - Segmental mediolytic arteriopathy (SMA) is a newly described and uncommon variant
      of arterial fibromuscular dysplasia that affects principally visceral small and
      medium sized arteries. SMA is characterized by myolytic dysplasia of the arterial
      media, intramural dissection, and thrombosis or ruptured aneurysms resulting in
      visceral hemorrhage and infarction as the dire consequences. Because of its
      relative obscurity and frequent angiographic manifestation of microaneurysms,
      clinically SMA mimics polyarteritis nodosa, and the patient so diagnosed had been
      treated with immunosuppressive therapy with a catastrophic outcome. Five new
      cases of unsuspected SMA are described herein, three involving visceral arteries
      and, for the first time, one case each affecting the cerebral and pulmonary
      parenchymal arteries. Three of the five patients did not survive because SMA
      remained unrecognized until after death and a subsequent review of the biopsy and
      autopsy specimens. Death in each of the three patients was directly attributable
      to complications of SMA or indirectly to septic complications of the
      immunosuppressive therapy for the misdiagnosed vasculitis. Clinicians and
      pathologists alike should become better acquainted with this unusual form of
      noninflammatory arteriopathy, so as not to misdiagnose it as vasculitis. 

PMID- 25851788
TI  - Extensive myocytolysis as a marker of sudden cardiac death.
AB  - Colliquative myocytolysis, an intracellular vacuolization of myocardial cells, is
      considered an indicator of acute myocardial ischemia. Although often present in
      ischemic cardiac death, this lesion is often either overlooked, or not utilized
      as a criterion for diagnosing ischemia. This study reports light microscopic and
      ultrastructural studies of six autopsied patients who died suddenly and showed
      extensive myocytolysis as the only pathologic finding. In two of these patients,
      the clinical history and electrocardiogram findings documented an acute ischemic
      episode 1 to 3 hours antemortem. Six control patients with matched age and
      postmortem intervals did not show the intracellular vacuolization characteristic
      of myocytolysis. The postmortem intervals ranged from 2 to 12 hours.
      Ultrastructurally, myocytolysis was seen as a well-defined large intracellular
      vacuole without any lining membrane and associated with disrupted myofibrils,
      prominent Z band degeneration, and a few fat droplets. The mitochondria showed
      swelling and disruption, as well as electron dense amorphous inclusions. The
      swelling and disruption of mitochondria are well-known postmortem artefacts, and
      the mitochondrial amorphous inclusions, large intracellular vacuoles, prominent Z
      band degeneration, and fat droplets are not seen with autolysis. We conclude that
      myocytolysis, especially if extensive and restricted to an area supplied by a
      major coronary artery, can be a helpful pathologic marker of myocardial ischemia,
      particularly in sudden deaths without any other histologic findings. 

PMID- 25851789
TI  - Matrix metalloproteinases in the pathology of natural and bioprosthetic cardiac
      valves.
AB  - Degenerative dysfunction of cardiac valves may be accounted for by uncontrolled
      extracellular matrix degradation processes in which matrix metalloproteinases
      could play a major role. In this study, 24 pathologic human valves and 26
      pericardial-derived bioprostheses were analysed for metalloproteinases by gelatin
      zymography. Compared to controls, human stenotic valves and bioprostheses
      explanted because of either calcifying or noncalcifying degeneration revealed
      three notable biochemical aspects: (1) an amplification in the levels of
      metalloproteinase 9 (gelatinase B), suggestive of its active role in valvular
      pathology; (2) minimal modifications in the gelatinolytic levels of
      metalloproteinase 2 (gelatinase A), indicative of a constitutive secretion; and
      (3) activation products derived from both gelatinase A and B. All gelatinolytic
      activities identified in pathologic specimens were inhibited in vitro by zinc and
      calcium chelators (captopril, doxycycline, dithiothreitol, and
      ethylenediaminotetraacetic acid), suggesting potential therapeutic approaches.
      High levels of beta-glucuronidase (a lysosomal marker enzyme for phagocytic
      cells) were found in human calcified stenotic valves and in ruptured and
      calcified pericardial-derived bioprostheses. Mononuclear recruitment was minimal
      to moderate in pathologic human valves, and in noncalcified ruptured
      bioprostheses infiltrating mononuclear cells were concentrated in large numbers
      at the cuspal free edge. These findings suggest the involvement of infiltrating
      phagocytic cells and putative common mechanisms in the degeneration of both the
      natural and the bioprosthetic valvular extracellular matrix (ECM). 

PMID- 25851790
TI  - Myocardial extramedullary hematopoiesis following myocardial infarction.
AB  - Extramedullary hematopoiesis (EMH) usually accompanies a chronic hematologic
      disease in adults or prematurity in neonates. We observed a striking case of EMH
      in the explanted heart of a 13-year-old boy who underwent transplantation after
      extensive myocardial infarction. The florid myeloid proliferation raised the
      possibility of a leukemic process. To our knowledge, extensive myocardial EMH
      subsequent to myocardial infarction has not been previously reported. Possible
      mechanisms underlying EMH in the myocardium are presented. 

PMID- 25851791
TI  - Pharmacology and controlled release of hirudin for cardiovascular disorders.
AB  - Hirudin is the most potent specific inhibitor of thrombin known. Hirudin was
      originally isolated from leeches, but it is now also available in synthetic form
      (recombinant hirudin). The inhibitor is currently undergoing clinical trials as a
      potential replacement for the extensively used thrombin inhibitor heparin. In
      this review, the biochemical and pharmacokinetic characteristics of hirudin
      (native and recombinant) and the efficacy of hirudin in treating and preventing
      cardiovascular disorders is discussed. The advantages of local controlled
      delivery of hirudin for treating cardiovascular disorders are then presented.
      Several implantable polymers applicable for controlled delivery system also are
      introduced. Finally, the feasibility of controlled delivery of r-hirudin for
      local therapy of cardiovascular disorders is addressed. 

PMID- 25851792
TI  - Nationwide survey of Cockayne syndrome in Japan: Incidence, clinical course and
      prognosis.
AB  - In the first nationwide survey of Cockayne syndrome (CS) in Japan, the incidence
      of CS was estimated to be 2.77 per million births (95%CI: 2.19-3.11) and the
      prevalence was approximately 1 in 2,500,000. A total of 47 CS patients (24
      surviving and 23 deceased) were identified. Based on clinical course, these 47
      patients were classified into CS type 1 (n = 41; 21 surviving, 20 deceased), CS
      type 2 (n = 2; all deceased), CS type 3 (n = 3; all surviving), and CS/xeroderma
      pigmentosum type D (n = 1, deceased). In the 41 CS type 1 patients, seven
      findings (i.e. failure to thrive; photosensitivity; deafness; characteristic
      facial appearance of CS [sunken eyes]; foot joint contracture; intellectual
      disability; and basal ganglia calcification on computed tomography [CT]) were
      observed in >90% of patients. Of these, failure to thrive, photosensitivity, and
      intellectual disability (language delays) developed before 2 or 3 years of age,
      whereas deafness, sunken eyes, and basal ganglia calcification on CT occurred
      later. Features such as bodyweight and height stagnation, language delay,
      abnormal nutritional pathways (tube feeding), and renal failure were more
      prominent in the 20 deceased CS type 1 patients than in the 21 surviving CS type
      1 patients. Of the 20 deceased CS type 1 patients, nine developed severe renal
      failure during the terminal stages of their condition. The present findings
      suggest that the clinical course of CS includes a diverse range of symptoms, but
      each type has characteristic symptoms. In addition, the management of renal
      failure and nutrition are very important for ensuring good quality of life
      throughout the long-term course of CS.

PMID- 25851793
TI  - A novel autonomous real-time position method based on polarized light and
      geomagnetic field.
AB  - Many animals exploit polarized light in order to calibrate their magnetic
      compasses for navigation. For example, some birds are equipped with biological
      magnetic and celestial compasses enabling them to migrate between the Western and
      Eastern Hemispheres. The Vikings' ability to derive true direction from polarized
      light is also widely accepted. However, their amazing navigational capabilities
      are still not completely clear. Inspired by birds' and Vikings' ancient
      navigational skills. Here we present a combined real-time position method based
      on the use of polarized light and geomagnetic field. The new method works
      independently of any artificial signal source with no accumulation of errors and
      can obtain the position and the orientation directly. The novel device simply
      consists of two polarized light sensors, a 3-axis compass and a computer. The
      field experiments demonstrate device performance. 

PMID- 25851794
TI  - Evidence That High Catecholamine Levels Produced by Pheochromocytoma May be
      Responsible for Tako-Tsubo Cardiomyopathy.
AB  - Tako-tsubo cardiomyopathy (TC) is a novel form of acute heart failure,
      characterized by regional left ventricular dysfunction without coronary artery
      obstruction, and usually triggered by a stressful event. Excessive circulating
      catecholamines have been implicated in the pathophysiology of this condition.
      This report documents the unusual occurrence of acute TC events in 2 male
      subjects of disparate ages, 16 and 66 years, for whom subsequent investigation in
      both led to the unexpected discovery of catecholamine-producing pheochromocytoma.
      Marked elevation of plasma catecholamines (epinephrine, norepinephrine, and
      dopamine) was present in both subjects and were remarkably similar to those
      previously reported in female patients with TC triggered by emotional stress.
      These observations show a common link between TC occurrence and elevated
      catecholamine levels in both male and female patients and, therefore, support the
      hypothesis that excessive levels of catecholamines may be involved in the
      pathophysiology of TC independent of age or gender. 

PMID- 25851795
TI  - Outcomes and computed tomography scan follow-up of bioresorbable vascular
      scaffold for the percutaneous treatment of chronic total coronary artery
      occlusion.
AB  - Everolimus-eluting bioresorbable vascular scaffold (BVS) implantation in chronic
      total occlusion (CTO) could provide theoretical advantages at follow-up compared
      with metallic stents. This study aimed to assess the feasibility of BVS use for
      the percutaneous treatment of CTO by analyzing clinical outcomes and patency at
      midterm follow-up. From February 2013 to June 2014, 42 patients with 46 CTOs were
      treated by BVS implantation. Once the guidewire reached the distal lumen, all the
      occluded segments were predilated. Postdilation was performed in all patients. A
      multislice computed tomography was scheduled for all patients at 6 months. The
      mean age was 58 +/- 9 years, 41 (98%) were men and 14 (33%) diabetic. The target
      vessel was predominantly the left anterior descending artery (22, 48%). According
      to the Japanese-CTO score, 21 CTOs (46%) were difficult or very difficult. Most
      cases were treated with an anterograde strategy (34 lesions, 74%). A hybrid
      procedure with a drug-eluting stent at the distal segment was the applied
      treatment in 7 CTOs (15%). The mean scaffold length was 43 +/- 21 mm. Technical
      success was achieved in 45 lesions (98%), and 1 patient (2.4%) presented a non-Q
      periprocedural myocardial infarction. Re-evaluation was obtained in all patients
      at 6 +/- 1 months. Two re-occlusions and a focal restenosis were identified.
      After 13 +/- 5 months of follow-up, there were 2 repeat revascularizations
      (4.8%). Neither death nor myocardial infarction was documented. In conclusion,
      BVS for CTO seems to be an interesting strategy with a high rate of technical
      success and low rate of cardiac events at midterm follow-up in selected patients.

PMID- 25851796
TI  - Usefulness of cardiac meta-iodobenzylguanidine imaging to identify patients with
      chronic heart failure and left ventricular ejection fraction <35% at low risk for
      sudden cardiac death.
AB  - Patients with chronic heart failure (CHF) at risk of sudden cardiac death (SCD)
      are often treated with implantable cardiac defibrillators (ICDs). However,
      current criteria for device use that is based largely on left ventricular
      ejection fraction (LVEF) lead to many patients receiving ICDs that never deliver
      therapy. It is of clinical significance to identify patients who do not require
      ICDs. Although cardiac I-123 meta-iodobenzylguanidine (MIBG) imaging provides
      prognostic information about CHF, whether it can identify patients with CHF who
      do not require an ICD remains unclear. We studied 81 patients with CHF and LVEF
      <35%, assessed by cardiac MIBG imaging at enrollment. The heart-to-mediastinal
      ratio (H/M) in delayed images and washout rates were divided into 6 grades from 0
      to 5, according to the degree of deviation from control values. The study
      patients were classified into 3 groups: low (1 to 4), intermediate (5 to 7), and
      high (8 to 10), according to the MIBG scores defined as the sum of the H/M and
      washout rate scores. Sixteen patients died of SCD during a follow-up period.
      Patients with low MIBG score had a significantly lower risk of SCD than those
      with intermediate and high scores (low [n = 19], 0%; intermediate [n = 37], 19%;
      high [n = 25], 36%; p = 0.001). The positive predictive value of low MIBG score
      for identifying patients without SCD was 100%. In conclusion, the MIBG score can
      identify patients with CHF and LVEF <35% who have low risk of developing SCD. 

PMID- 25851797
TI  - Irregular Rhythms and Wide QRS Complexes.

PMID- 25851798
TI  - Multiple biomarkers including cardiac troponins T and I measured by high
      sensitivity assays, as predictors of long-term mortality in patients with chronic
      renal failure who underwent dialysis.
AB  - There is a high cardiac mortality in patients on long-term renal dialysis. No
      studies have reported long-term outcomes relating to both high-sensitivity
      cardiac troponin T (hs-cTnT) and high-sensitivity cardiac troponin I (hs-cTnI) in
      these patients. Patients who underwent long-term dialysis at the Canberra
      Hospital had blood samples collected for both cardiac and other biomarkers.
      Samples were stored at -80 degrees C until analysis. Mortality data were
      collected at 5 years, and univariate and multivariate analyses were performed to
      identify which biomarkers were predictive of mortality at 5 years. After
      multivariate analysis, albumin, C-reactive protein (CRP), and hs-cTnT remained
      independently predictive of all-cause mortality, with hs-cTnT having the highest
      hazard ratio. If hs-cTnT was excluded from the analysis, then hs-cTnI was
      independently predictive of mortality. For hs-cTnT, for both genders, the ninety
      ninth percentile, derived from a population with subjects with subclinical
      disease excluded, served as an excellent partition between survivors and
      nonsurvivors. Receiver-operating characteristic curve analysis for hs-cTnT had
      area under the curve of 0.798 and for hs-cTnI of 0.774. Kaplan-Meier curves for
      the aggregation of albumin, CRP, and hs-cTnT showed a stronger predictive power
      with receiver-operating characteristic area under the curve of 0.805. The
      addition of echocardiographic data in an analysis of all patients who had an
      echocardiogram for clinical reasons (n = 105) did not alter the final
      observations in this subgroup. In conclusion, hs-cTnT retains a superior
      predictive power in a dialysis-dependent population for identifying those at risk
      for death and when aggregated with albumin and CRP also has substantial additive
      value for identifying mortality risk in a renal-dialysis population. 

PMID- 25851799
TI  - National Voluntary Public Health Accreditation: Are More Local Health Departments
      Intending to Take Part?
AB  - OBJECTIVE: This article examines local health department (LHD) participation and
      intentions to participate in national voluntary accreditation and reasons for not
      seeking accreditation. Specifically, it compares the results of national surveys
      among LHDs in 2010, 2013, and 2014. DESIGN: Longitudinal cohort study. SETTING:
      United States. PARTICIPANTS: LHDs that responded to the 2014 Forces of Change
      Survey and the 2010 and 2013 National Association of County and City Health
      Officials Profile studies. MAIN OUTCOME MEASURES: LHD level of engagement in
      Public Health Accreditation Board (PHAB) accreditation. RESULTS: Data of 2014
      indicated that 1% of LHDs achieved accreditation and 11% had submitted an
      application or a statement of intent, compared with 6% of LHDs that submitted an
      application or a statement of intent in 2013. The percent of LHDs that indicated
      they planned to apply for accreditation but had not submitted a statement of
      intent declined from 27% in 2013 to 22% in 2014. In multivariate models,
      controlling for governance category and jurisdiction population size, LHDs in
      states where the state health department (SHD) participated in e-PHAB had higher
      odds of being favorably inclined toward accreditation than those located in
      states where the SHD was not in the e-PHAB system (odds ratio = 2.82, 95%
      confidence interval: 1.81-4.41). Across 2013 and 2014, and across small and large
      LHDs, the top 2 reasons for deciding not to apply for accreditation were the
      time/effort required exceeded the benefits (67%) and fees were too high (46%).
      CONCLUSIONS: SHDs are powerful mediators of LHDs' perceptions of the PHAB
      accreditation program. Health department governance structure and jurisdiction
      population size are associated with LHD accreditation participation decisions.
      With the launch of PHAB's program, fewer LHDs are undecided about accreditation
      participation and many have taken affirmative steps to become accredited. The top
      2 reasons LHDs indicated for not proceeding with accreditation were time/effort
      exceed benefit and fees perceived as too high.

PMID- 25851800
TI  - Dabigatran versus warfarin major bleeding in practice: an observational
      comparison of patient characteristics, management and outcomes in atrial
      fibrillation patients.
AB  - Data comparing the patient characteristics, management and outcomes for
      dabigatran versus warfarin major bleeding in the practice setting are limited. We
      performed a retrospective single health system study of atrial fibrillation
      patients with dabigatran or warfarin major bleeding from October 2010 through
      September 2012. Patient identification occurred through both an internal adverse
      event reporting system and a structured stepwise data filtering approach using
      the International Classification of Diseases diagnosis codes. Thirty-five
      dabigatran major bleeding patients were identified and compared to 70 warfarin
      major bleeding patients. Intracranial bleed occurred in 4.3 % of warfarin
      patients and 8.6 % of dabigatran patients. Dabigatran patients tended to be older
      (79.9 vs. 76 years) and were more likely to have a creatinine clearance of 15-30
      mL/min (40 vs. 18.6 %, p = 0.02). Over one-third of dabigatran patients had an
      excessive dose based on renal function. More dabigatran patients required a
      procedure for bleed management (37.1 vs. 17.1 %, p = 0.03) and received a
      hemostatic agent for reversal (11.4 vs. 1.4 %, p = 0.04). Dabigatran patients
      were twice as likely to spend time in an ICU (45.7 vs. 27.1 %, p = 0.06), be
      placed in hospice/comfort care (14.3 vs. 7.1 %, p = 0.24), expire during
      hospitalization (14.3 vs. 7.1 %, p = 0.24), and expire within 30-days (22.9 vs.
      11.4 %, p = 0.28). In a single hospital center practice setting, as compared to
      warfarin, patients with dabigatran major bleeding were more likely to be older,
      have renal impairment, require a procedure for bleed management and receive a
      hemostatic agent. Patients with dabigatran major bleeding had an excessive dose
      for renal function in more than one-third of cases.

PMID- 25851801
TI  - Regarding: Ko JH, et al.: Clinical features and risk factors for development of
      Bacillus bacteremia among adult patients with cancer: a case-control study. Supp
      Care Cancer 2015;23(2):377-84.

PMID- 25851802
TI  - Aprepitant as an add-on therapy in children receiving highly emetogenic
      chemotherapy: a randomized, double-blind, placebo-controlled trial.
AB  - BACKGROUND: Aprepitant, a neurokinin-1 receptor antagonist, in combination with 5
      HT-3 antagonist and dexamethasone is recommended in adults receiving moderately
      and highly emetogenic chemotherapy to reduce chemotherapy-induced vomiting (CIV).
      Data for use of aprepitant in children is limited and hence aprepitant is not
      recommended by Pediatric Oncology Group of Ontario guidelines for prevention of
      CIV in children <12 years. METHODS: A randomized, double-blind, placebo
      controlled trial was conducted at a single center in chemotherapy naive children
      (5-18 years) receiving highly emetogenic chemotherapy. All patients received
      intravenous ondansetron (0.15 mg/kg) and dexamethasone (0.15 mg/kg) prior to
      chemotherapy followed by oral ondansetron and dexamethasone. Patients randomly
      assigned to aprepitant arm received oral aprepitant (15-40 kg = days 1-3, 80 mg;
      41-65 kg = day 1, 125 mg and days 2-3, 80 mg) 1 h before chemotherapy. Control
      group received placebo as add-on therapy. Primary outcome measure was the
      incidence of acute moderate to severe vomiting, which was defined as more than
      two vomiting episodes within 24 h after the administration of the first
      chemotherapy dose until 24 h after the last chemotherapy dose in the block.
      Complete response (CR) was defined as absence of vomiting and retching during the
      specified phase. RESULTS: Of the 96 randomized patients, three were excluded from
      analysis; 93 patients were analyzed (50 in aprepitant arm and 43 in placebo arm).
      Acute moderate and severe vomiting was reported in 72 % patients receiving
      placebo and 38 % patients receiving aprepitant (p = 0.001). Complete response
      rates during acute phase were significantly higher in aprepitant arm (48 vs. 12
      %, p < 0.001). No major adverse effects were reported by patients/guardians.
      CONCLUSIONS: This double-blind, randomized, placebo-controlled trial shows that
      aprepitant significantly decreases the incidence of CIV during acute phase when
      used as an add-on drug with ondansetron and dexamethasone in children receiving
      highly emetogenic chemotherapy.

PMID- 25851803
TI  - Head and neck cancer patients' perceptions of swallowing following
      chemoradiotherapy.
AB  - PURPOSE: The study aims to describe patients' experiences of swallowing
      difficulties following (chemo)radiotherapy for head and neck cancer and to
      explore any changes over time. METHODS: A purposive sample of patients with
      swallowing difficulties was selected at a range of time points, from 3 to 18
      months following treatment. Ethnographic observations of 12 patients were
      conducted in their own homes, over a mealtime situation. Nine new patients were
      interviewed about changes to their eating and drinking from pre- to post
      treatment. Thematic analysis was used to code and analyse the data. RESULTS:
      Patients' reports of swallowing function were divided into four time zones: pre
      treatment, during radiotherapy, early (0-3 months) and late (6-18 months) time
      points following treatment. The majority reported minimal problems at diagnosis,
      but marked impairment during and after radiotherapy, without a return to pre
      treatment functioning. The focus was on severe physical side effects and changes
      to food preparation during radiotherapy and in the early phase of recovery. By 6
      months, side effects began to subside, but swallowing was still difficult,
      leading to major changes to family life, socialisation and lifestyle.
      CONCLUSIONS: Swallowing problems after (chemo)radiotherapy are multi-faceted and
      highly individualised and restrict lives in the long term. Swallowing ability may
      improve in time, but does not appear to return to pre-treatment function. Further
      work is required to find ways of being able to best support patients living with
      this long-term condition.

PMID- 25851804
TI  - The eating experience in long-term survivors of head and neck cancer: a mixed
      methods study.
AB  - PURPOSE: This study explored the eating experience in long-term survivors of head
      and neck cancer (HNC) >=3 years post concurrent chemoradiation. Quality of life
      (QOL) and the meanings and perceptions survivors had as it related to the eating
      experience were explored. METHODS: Purposive sampling was utilized; 10 long-term
      survivors of HNC participated in the study. A mixed-methods approach was used;
      exploratory qualitative research using content analysis and summary statistics
      was used to describe demographic and clinical characteristics and the Vanderbilt
      Head and Neck Symptom Survey version 2.0 scores (VHNSS 2.0). RESULTS: Four
      categories (psychological, social impact, functional status, and the current
      eating experience) containing 15 subthemes and 1 overarching theme (adaptation)
      emerged. Current health status, QOL, and QOL related to eating were viewed
      favorably despite the impact of treatment late effects on participants' daily
      lives. Adaptation and maladaptation in regard to food choice and downplaying of
      symptoms were recognized. Interviews as well as the VHNSS 2.0 scores indicated
      that xerostomia, mucosal sensitivity, swallowing difficulty, length of time
      required to eat, and dysgeusia remained problematic. CONCLUSION: Psychological,
      functional, and social losses associated with eating were identified.
      Participants modify or avoid foods that are challenging yet report enjoyment with
      eating. Challenges with eating were downplayed. Due to the potential negative
      nutritional and social implications of avoiding specific food/food groups,
      standard of care in long-term survivors of HNC should include assessment of the
      eating experience and functional challenges. Nutrition professional can help
      patients optimize dietary intake and the eating experience.

PMID- 25851805
TI  - Developmental trajectories for attention and working memory in healthy Japanese
      school-aged children.
AB  - OBJECTIVE: The aim of this study was to investigate the developmental
      trajectories of attention, short-term memory, and working memory in school-aged
      children using a 10 min test battery of cognitive function. METHODS: Participants
      comprised 144 typically developing children (TDC) aged 7-12 years and 24 healthy
      adults, divided according to age into seven groups (12 males and 12 females for
      each age group). Participants were assessed using CogHealth, which is a computer
      based measure composed of five tasks. We measured attention, short-term memory,
      and working memory (WM) with visual stimulation. Each task was analyzed for age
      related differences in reaction time and accuracy rate. RESULTS: Attention tasks
      were faster in stages from the age of 7-10 years. Accuracy rate of short-term
      memory gradually increased from 12 years of age and suddenly increased and
      continued to increase at 22 years of age. Accuracy rate of working memory
      increased until 12 years of age. Correlations were found between the ages and
      reaction time, and between ages and accuracy rate of the tasks. CONCLUSION: These
      results indicate that there were rapid improvements in attention, short-term
      memory, and WM performance between 7 and 10 years of age followed by gradual
      improvement until 12 years of age. Increase in short-term memory continued until
      22 years of age. In our experience CogHealth was an easy and useful measure for
      the evaluation of cognitive function in school-age children.

PMID- 25851806
TI  - Five Chinese patients with 5-oxoprolinuria due to glutathione synthetase and 5
      oxoprolinase deficiencies.
AB  - OBJECTIVE: 5-Oxoprolinuria is a rare inherited metabolic disorder caused by a
      defective gamma-glutamyl cycle resulting from mutations in the genes encoding 5
      oxoprolinase (OPLAH) and glutathione synthetase (GSS). No inherited 5
      oxoprolinuria case has been reported in mainland China until now. In this study,
      clinical, biochemical, and genetic aspects of five Chinese 5-oxoprolinuria
      patients with OPLAH or GSS gene mutations were investigated. METHODS: Three boys
      and two girls from five unrelated Chinese families with symptomatic 5
      oxoprolinuria were identified within the past 3years in Peking University First
      Hospital. OPLAH and GSS genes were analyzed. RESULTS: Patients were hospitalized
      between the age of 13days to 1year and 3months for hypersomnia, developmental
      retardation, feeding deficiency, vomiting, icterus and recurrent pneumonia. All
      patients had significantly elevated urine 5-oxoproline. Three novel mutations
      (c.1904G>A and c.2813_2815delGGG in Patient 1, c.2978G>T in Patient 2) on OPLAH,
      on GSS, one novel mutation (c.1252C>T in Patient 3) and a reported mutation
      (c.491G>A in Patients 3-5) were detected. Patient 4 has homozygous mutation
      c.491G>A, the others are heterozygous. After treatment by l-carnitine, vitamin E,
      B1, B2 and coenzyme Q10, three patients with GSS deficiency improved, but the two
      5-oxoprolinase-deficient patients did not respond to treatment. CONCLUSIONS: 5
      Oxoprolinase deficiency and GSS deficiency share some clinical and biochemical
      features. Genetic analysis is important for the deferential diagnosis. In this
      study, five Chinese patients had severe central nervous system damage.
      Antioxidant treatments were proved effective for the three patients with GSS
      deficiency but not for the two patients with 5-oxoprolinase deficiency.

PMID- 25851807
TI  - Aerobic sludge granulation at high temperatures for domestic wastewater
      treatment.
AB  - With inoculum sludge from a conventional activated sludge wastewater treatment
      plant, three sequencing batch reactors (SBRs) fed with synthetic wastewater were
      operated at different high temperatures (30, 40 and 50+/-1 degrees C) to study
      the formation of aerobic granular sludge (AGS) for simultaneous organics and
      nutrients removal with a complete cycle time of 3h. The AGS were successfully
      cultivated with influent loading rate of 1.6CODg(Ld)(-1). The COD/N ratio of the
      influent wastewater was 8. The results revealed that granules developed at 50
      degrees C have the highest average diameter, (3.36mm) with 98.17%, 94.45% and
      72.46% removal efficiency observed in the system for COD, ammonia and phosphate,
      respectively. This study also demonstrated the capabilities of AGS formation at
      high temperatures which is suitable to be applied for hot climate conditions. 

PMID- 25851808
TI  - Therapeutic plasma exchange as a steroid-sparing therapy in a patient with limbic
      encephalitis due to antibodies to voltage-gated potassium channels.
AB  - Autoantibodies to the voltage-gated potassium channel (VGKC) complex cause a
      spectrum of non-paraneoplastic neurologic syndromes including limbic encephalitis
      (LE). We report a case of a man with LE who underwent a course of therapeutic
      plasma exchange (TPE) in addition to other immunomodulatory therapies and
      experienced sustained clinical resolution of his symptoms. This report adds to
      the existing literature supporting TPE in cases of LE due to VGKC complex
      autoantibodies.

PMID- 25851809
TI  - First report of inhibitory von Willebrand factor alloantibodies in type 2B von
      Willebrand disease.

PMID- 25851811
TI  - Cyst infection in autosomal dominant polycystic kidney disease: causative
      microorganisms and susceptibility to lipid-soluble antibiotics.
AB  - Cyst infection is a frequent and serious complication of autosomal dominant
      polycystic kidney disease (ADPKD). Lipid-soluble antibiotics like
      fluoroquinolones show good penetration into cysts and are recommended for cyst
      infection, but causative microorganisms are often resistant to these agents. This
      study investigated the profile of the microorganisms causing cyst infection in
      ADPKD, their susceptibility to lipid-soluble antibiotics, and clinical outcomes.
      This retrospective study reviewed all ADPKD patients admitted to Toranomon
      Hospital with a diagnosis of cyst infection from January 2004 to March 2014. All
      patients who underwent cyst drainage and had positive cyst fluid cultures were
      enrolled. Patients with positive blood cultures who satisfied our criteria for
      cyst infection or probable infection were also enrolled. There were 99 episodes
      with positive cyst fluid cultures and 93 episodes with positive blood cultures.
      The majority of patients were on dialysis. The death rate was high when infection
      was caused by multiple microorganisms or when there were multiple infected cysts.
      Gram-negative bacteria accounted for 74-79 % of the isolates in all groups,
      except for patients with positive hepatic cyst fluid cultures. The susceptibility
      of Escherichia coli to fluoroquinolones was very low in patients with hepatic
      cyst infection, especially those with frequent episodes and those with
      hepatomegaly. Fungi were detected in two episodes. Fluoroquinolone-resistant
      microorganisms showed a high prevalence in cyst infection. It is important to
      identify causative microorganisms to avoid the overuse of fluoroquinolones and to
      improve the outcome of cyst infection in ADPKD. 

PMID- 25851810
TI  - The E3 ubiquitin ligase Trim7 mediates c-Jun/AP-1 activation by Ras signalling.
AB  - The c-Jun/AP-1 transcription factor controls key cellular behaviours, including
      proliferation and apoptosis, in response to JNK and Ras/MAPK signalling. While
      the JNK pathway has been well characterized, the mechanism of activation by Ras
      was elusive. Here we identify the uncharacterized ubiquitin ligase Trim7 as a
      critical component of AP-1 activation via Ras. We found that MSK1 directly
      phosphorylates Trim7 in response to direct activation by the Ras-Raf-MEK-ERK
      pathway, and this modification stimulates Trim7 E3 ubiquitin ligase activity.
      Trim7 mediates Lys63-linked ubiquitination of the AP-1 co-activator RACO-1,
      leading to RACO-1 protein stabilization. Consequently, Trim7 depletion reduces
      RACO-1 levels and AP-1-dependent gene expression. Moreover, transgenic
      overexpression of Trim7 increases lung tumour burden in a Ras-driven cancer
      model, and knockdown of Trim7 in established xenografts reduces tumour growth.
      Thus, phosphorylation-ubiquitination crosstalk between MSK1, Trim7 and RACO-1
      completes the long sought-after mechanism linking growth factor signalling and AP
      1 activation. 

PMID- 25851812
TI  - Design and validation of a qPCR assay for accurate detection and initial
      serogrouping of Legionella pneumophila in clinical specimens by the ESCMID Study
      Group for Legionella Infections (ESGLI).
AB  - Prompt detection of Legionella pneumophila is essential for rapid investigation
      of legionellosis. Furthermore, as the majority of L. pneumophila infections are
      caused by serogroup 1 (sg1) strains, rapid identification of such strains can be
      critical in both routine and outbreak scenarios. The ESCMID Study Group for
      Legionella Infections (ESGLI) was established in 2012 and immediately identified
      as a priority the validation of a reliable, easy to perform and interpret, cost
      effective qPCR assay to standardise the detection of L. pneumophila DNA amongst
      members. A novel L. pneumophila assay targeting the mip gene was designed and
      combined with previously published methodologies amplifying the sg1 marker (wzm)
      and the green fluorescent protein gene (gfp) internal process control. The
      resulting triplex assay was validated internationally on the three qPCR platforms
      used by the majority of European Legionella reference laboratories: ABI 7500
      (Life Technologies), LightCycler 480 Instrument II (Roche) and Rotor-Gene Q
      (Qiagen). Clinical and EQA specimens were tested together with a large panel of
      strains (251 in total) to validate the assay. The assay proved to be 100%
      specific for L. pneumophila and sg1 DNA both in silico and in vitro. Efficiency
      values for mip and wzm assays ranged between 91.97 and 97.69%. Limit of detection
      values estimated with 95% confidence were adopted for mip and wzm assays on all
      three qPCR platforms. Inhibition was not observed. This study describes a robust
      assay that could be widely implemented to standardise the molecular detection of
      L. pneumophila among ESGLI laboratories and beyond.

PMID- 25851813
TI  - Spontaneous Parahisian Accessory Pathway Activity.

PMID- 25851816
TI  - From bacteria to mollusks: the principles underlying the biomineralization of
      iron oxide materials.
AB  - Various organisms possess a genetic program that enables the controlled formation
      of a mineral, a process termed biomineralization. The variety of biological
      material architectures is mind-boggling and arises from the ability of organisms
      to exert control over crystal nucleation and growth. The structure and
      composition of biominerals equip biomineralizing organisms with properties and
      functionalities that abiotically formed materials, made of the same mineral,
      usually lack. Therefore, elucidating the mechanisms underlying biomineralization
      and morphogenesis is of interdisciplinary interest to extract design principles
      that will enable the biomimetic formation of functional materials with similar
      capabilities. Herein, we summarize what is known about iron oxides formed by
      bacteria and mollusks for their magnetic and mechanical properties. We describe
      the chemical and biological machineries that are involved in controlling mineral
      precipitation and organization and show how these organisms are able to form
      highly complex structures under physiological conditions. 

PMID- 25851818
TI  - Impact of early haemodynamic goal-directed therapy in patients undergoing
      emergency surgery: an open prospective, randomised trial.
AB  - Haemodynamic goal-directed therapies (GDT) may improve outcome following elective
      major surgery. So far, few data exist regarding haemodynamic optimization during
      emergency surgery. In this randomized, controlled trial, 50 surgical patients
      with hypovolemic or septic conditions were enrolled and we compared two
      algorithms of GDTs based either on conventional parameters and pressure pulse
      variation (control group) or on cardiac index, global end-diastolic volume index
      and stroke volume variation as derived from the PiCCO monitoring system
      (optimized group). Postoperative outcome was estimated by a composite index
      including major complications and by the Sequential Organ Failure Assessment
      (SOFA) Score within the first 3 days after surgery (POD1, POD2 and POD3). Data
      from 43 patients were analyzed (control group, N = 23; optimized group, N = 20).
      Similar amounts of fluid were given in the two groups. Intraoperatively,
      dobutamine was given in 45 % optimized patients but in no control patients. Major
      complications occurred more frequently in the optimized group [19 (95 %) versus
      10 (40 %) in the control group, P < 0.001]. Likewise, SOFA scores were higher in
      the optimized group on POD1 (10.2 +/- 2.5 versus 6.6 +/- 2.2 in the control
      group, P = 0.001), POD2 (8.4 +/- 2.6 vs 5.0 +/- 2.4 in the control group, P =
      0.002) and POD 3 (5.2 +/- 3.6 and 2.2 +/- 1.3 in the control group, P = 0.01).
      There was no significant difference in hospital mortality (13 % in the control
      group and 25 % in the optimized group). Haemodynamic optimization based on
      volumetric and flow PiCCO-derived parameters was associated with a less favorable
      postoperative outcome compared with a conventional GDT protocol during emergency
      surgery. 

PMID- 25851819
TI  - Metabolic activation of furan moiety makes Diosbulbin B hepatotoxic.
AB  - Diosbulbin B (DIOB), a furanoid, is a major constituent of herbal medicine
      Dioscorea bulbifera L. Exposure to DIOB caused liver injury in humans and
      experimental animals. The mechanisms of DIOB-induced hepatotoxicities remain
      unknown. The present study demonstrated that DIOB induced hepatotoxicities in a
      time- and dose-dependent manner in mice. H&E stained histopathologic image showed
      the occurrence of necrosis in the liver obtained from the mice treated with DIOB
      at dose of 200 mg/kg. Pretreatment with KTC protected the animals from
      hepatotoxicities and hepatic GSH depletion induced by DIOB, increased area under
      the concentration-time curve of blood DIOB, decreased urinary excretion of GSH
      conjugates derived from DIOB, and increased urinary excretion of parent drug.
      Pretreatment with BSO exacerbated DIOB-induced hepatotoxicities. In order to
      define the role of furan moiety in DIOB-induced liver toxicities, we replaced the
      furan of DIOB with a tetrahydrofuran group by chemical hydrogenation of the furan
      ring of DIOB. No liver injury was observed in the animals given the same doses of
      tetrahydro-DIOB. The furan moiety was essential for DIOB-induced
      hepatotoxicities. The results implicate the cis-enedial reactive metabolite of
      DIOB was responsible for the observed toxicities. The observed modest depletion
      of hepatic GSH in DIOB-treated animals suggests the actions of one or more
      reactive metabolites, and the hepatic injury observed could be due at least in
      part to reactions of these metabolites with crucial biomolecules. Cytochrome P450
      3A enzymes are implicated in DIOB-induced hepatotoxicities by catalyzing the
      formation of the reactive metabolite of DIOB. 

PMID- 25851820
TI  - From smoking guns to footprints: mining for critical events of toxicity pathways
      in transcriptome data.

PMID- 25851822
TI  - Developing tools for defining and establishing pathways of toxicity.

PMID- 25851821
TI  - MPTP's pathway of toxicity indicates central role of transcription factor SP1.
AB  - Deriving a Pathway of Toxicity from transcriptomic data remains a challenging
      task. We explore the use of weighted gene correlation network analysis (WGCNA) to
      extract an initial network from a small microarray study of MPTP toxicity in
      mice. Five modules were statistically significant; each module was analyzed for
      gene signatures in the Chemical and Genetic Perturbation subset of the Molecular
      Signatures Database as well as for over-represented transcription factor binding
      sites and WGCNA clustered probes by function and captured pathways relevant to
      neurodegenerative disorders. The resulting network was analyzed for transcription
      factor candidates, which were narrowed down via text-mining for relevance to the
      disease model, and then combined with the large-scale interaction FANTOM4
      database to generate a genetic regulatory network. Modules were enriched for
      transcription factors relevant to Parkinson's disease. Transcription factors
      significantly improved the number of genes that could be connected in a given
      component. For each module, the transcription factor that had, by far, the
      highest number of interactions was SP1, and it also had substantial experimental
      evidence of interactions. This analysis both captures much of the known biology
      of MPTP toxicity and suggests several candidates for further study. Furthermore,
      the analysis strongly suggests that SP1 plays a central role in coordinating the
      cellular response to MPTP toxicity.

PMID- 25851824
TI  - Jejunal Intussusception in Peutz-Jeghers Syndrome Mimicking Acute Appendicitis.

PMID- 25851823
TI  - Tuberculous Epididymitis: A Case of Tuberculous Epididymitis That Was the
      Presenting Manifestation of Extrapulmonary and Pulmonary Tuberculoses.

PMID- 25851825
TI  - Cystic Adventitial Disease.

PMID- 25851826
TI  - Bodily pain intensity in nursing home residents with pressure ulcers: analysis of
      national minimum data set 3.0.
AB  - Clinical reports suggest that superficial pressure ulcers produce pain, but that
      pain decreases as the wound advances in stage. This study of the relationship
      between pressure ulcer stage and bodily pain intensity in nursing home residents
      was a secondary analysis of the national Minimum Data Set 3.0 assessment data in
      long-term care facilities, collected from nursing home residents at least 65
      years of age. Data were examined from residents with pressure ulcers who
      completed a bodily pain intensity interview between January and March 2012 (N =
      41,680) as part of the MDS comprehensive assessment. After adjusting for other
      variables (e.g., cognition, functional impairment, presence of comorbidities, use
      of scheduled pain medication, and sociodemographic variables), bodily pain
      intensity for those with more severe pressure ulcers in comparison to those with
      Stage I ulcers was higher by 11% (Stage II), 14% (Stage III), 24% (Stage IV), and
      22% (suspected deep tissue injury). Because multivariate analysis showed that
      greater bodily pain intensity was associated with an advanced stage of pressure
      ulcer, health care providers should assess bodily pain intensity and order
      appropriate pain management for nursing home residents with pressure ulcers,
      particularly for those with advanced pressure ulcers who are vulnerable to
      greater bodily pain intensity.

PMID- 25851827
TI  - Identification of a novel TMEM106B-ROS1 fusion variant in lung adenocarcinoma by
      comprehensive genomic profiling.
AB  - OBJECTIVES: ROS1-rearranged non-small cell lung cancer (NSCLC) is a unique
      molecularly defined yet heterogeneous subset of NSCLC. To date 12 known fusion
      partners of ROS1 in NSCLC have been reported. While crizotinib, a multi-targeted
      ALK/ROS1/MET tyrosine kinase inhibitor (TKI), has demonstrated significant
      clinical activity in ROS1-rearranged NSCLC, no companion diagnostic assay has
      been approved for the detection of ROS1-rearrange NSCLC by the US FDA.
      Comprehensive genomic profiling (CGP), a subtype of clinical next-generation
      sequencing (NGS), offers a uniquely comprehensive and convenient approach to
      detect the ever-increasing and "druggable" receptor-kinase rearrangements being
      discovered in lung cancer. MATERIALS AND METHODS: We identified a novel ROS1
      fusion variant (TMEM106B-ROS1) in a stage IV adenocarcinoma of the lung never
      smoker female patient during routine genomic profiling (FoundationOne). This
      novel TMEM106B-ROS1 fusion variant is generated by the fusion of exons 1-3 of
      TMEMB106B on chromosome 7p21 to the exons 35-43 of ROS1 on chromosome 6q22. The
      predicted TMEM106-ROS1 protein product contains 540 amino acids comprising of the
      N-terminal amino acids 1-73 of TMEMB106 and C-terminal amino acids of 1881-2341
      of ROS1. Although there is no predicted "coiled-coil" domain in the N-terminal
      domain of TMEM106B, the N-terminal domain of TMEM106B is involved in homo- and
      hetero-dimerization with other TMEM106 family members. CONCLUSIONS: TMEM106B-ROS1
      is a novel ROS1 fusion variant in NSCLC identified by comprehensive genomic
      profiling and should be included in any ROS1 detecting assay that depends on
      identifying the corresponding fusion partners such as reverse transcriptase
      polymerase chain reaction (RT-PCR).

PMID- 25851828
TI  - Do sleep complaints predict persistent fatigue in older adults?
AB  - OBJECTIVES: To examine the association between sleep complaints, use of sleep
      promoting medications, and persistent severe fatigue (PSF). DESIGN: Analysis of
      data from the National Health Aging Trends Study. SETTING: Contiguous United
      States. PARTICIPANTS: A representative sample of Medicare beneficiaries aged 65
      and older. MEASUREMENTS: Difficulty initiating sleep, difficulty staying asleep,
      use of sleep-promoting medications, demographic characteristics, presence of
      pain, use of pain medications, depression, chronic medical disease, physical
      activity level, and Short Physical Performance Battery score measured at
      baseline. The outcome of interest was PSF (fatigue that limits daily activities
      reported at baseline and 12-month follow-up). RESULTS: Of 8,245 participants at
      baseline, 7,075 completed 12-month follow-up; 31% reported severe fatigue at
      baseline and 31% at follow-up, and 19% reported PSF. In a logistic regression
      model, difficulty staying asleep some nights (odds ratio (OR) = 1.32, 95%
      confidence interval (CI) = 1.08-1.60) and most nights or every night (OR = 1.40,
      95% CI = 1.09-1.79) and use of sleep-promoting medications most nights or every
      night (OR = 1.35, 95% CI = 1.08-1.67) independently predicted PSF. CONCLUSION:
      The results indicate greater risk of PSF in older adults with difficulty staying
      asleep and those who use sleep-promoting medications. These findings underscore
      the significance of sleep problems and present potential targets for
      interventional studies that aim to improve fatigue in older adults.

PMID- 25851829
TI  - Increased risk of second primary malignancy in pediatric and young adult patients
      treated with radioactive iodine for differentiated thyroid cancer.
AB  - INTRODUCTION: The long-term sequelae of radioactive iodine (RAI) for
      differentiated thyroid cancer (DTC) in pediatric and young adult patients are not
      well-defined. Epidemiologic analyses of second primary malignancy (SPM) risk have
      only been performed in the adult population. Existing data are limited to case
      series with limited follow-up. The objective of this study was to analyze the
      elevated risk of SPM attributable to RAI in young patients treated for DTC.
      METHODS: Population-based analysis of 3850 pediatric and young adult patients
      (<25 years old) undergoing treatment with surgery with/without RAI for DTC,
      followed in the Surveillance, Epidemiology, and End Results cancer registry (1973
      2008), equating to 54,727 person-years at risk (PYR). The excess risk of SPM was
      calculated relative to a reference population and expressed as standardized
      incidence ratio (SIR) and excess absolute risk (EAR) per 10,000 PYR. Excess risk
      was compared in RAI-treated and non-RAI-treated patients. RESULTS: A total of
      1571 patients (40%) received RAI. The percentage of patients treated with RAI
      increased over time, from 4% in 1973 to 62% in 2008 (p<0.001). Among patients who
      received RAI, 26 SPMs were observed, and 18.3 were expected. The relative risk of
      SPM at any site was significantly elevated (SIR=1.42), corresponding to 4.4
      excess cases per 10,000 PYR. SPM risk was not elevated in the non-RAI-treated
      cohort (SIR=1.01, EAR=0). Patients treated with RAI were at dramatically elevated
      risk for development of a salivary malignancy (SIR=34.1), corresponding to 1.7
      excess cases per 10,000 PYR. The risk of leukemia in RAI-treated patients was
      elevated (SIR=4.0, EAR=0.9) but did not reach statistical significance. There was
      no elevated risk of salivary cancer or leukemia in the non-RAI-treated cohort.
      CONCLUSIONS: Pediatric and young adult patients who receive RAI for DTC
      experience an elevated risk of SPM, mainly salivary gland cancer. These risks
      appear to be only slightly higher than in adult patients. Over a decade,
      approximately 1 in 227 RAI-treated patients will develop an SPM, and 1 in 588 RAI
      treated patients will develop a salivary cancer, attributable to RAI. Because the
      expected survival time for young DTC patients is long, it is critical to weigh
      the benefits of RAI carefully against the small, but real, increase in SPM risk.

PMID- 25851830
TI  - Prediabetes, diagnosed and undiagnosed diabetes, their risk factors and
      association with knowledge of diabetes in rural Bangladesh: The Bangladesh
      Population-based Diabetes and Eye Study.
AB  - BACKGROUND: The aim of the present study was to determine the prevalence and risk
      factors of prediabetes and diagnosed and undiagnosed diabetes mellitus (DM) in
      rural Bangladesh. METHODS: Using a population-based cluster random sampling
      strategy, 3104 adults aged >=30 years were recruited. Fasting capillary blood
      glucose, blood pressure, height, weight, waist circumference, and knowledge,
      attitudes, and practice related to diabetes were recorded. Diabetes was defined
      as fasting glucose (FG) >=7.0 mmol/L or a self-reported diagnosis of diabetes;
      impaired FG (IFG) was defined as FG >= 6.1 and <7.0 mmol/L. RESULTS: The overall
      crude prevalence of DM was 7.2% (95% confidence interval [CI] 6.3%-8.1%; n =
      222), of which 55% (n = 123) was previously undiagnosed (UDM). The prevalence of
      IFG was 5.3% (95% CI 4.5%-6.1%; n = 163). The age-standardized prevalence of DM
      and IFG was 6.6% and 5.0%, respectively. The prevalence of UDM was higher in
      people of lower socioeconomic status (59% vs. 31%; P < 0.001). Of those with
      known DM, 56% had poor glycemic control (FG >= 7.0 mmol/L) and 37% were not on
      medication. Overall knowledge of DM was poor; only 16.3%, 17.8%, and 13.4% of
      those with UDM, IFG, and normal FG knew that diabetes causes eye disease,
      compared with 55.6% of those with known DM (Ptrend  < 0.001). CONCLUSIONS: In
      this rural Bangladeshi community, UDM was high. Lower socioeconomic status was
      associated with a higher risk of UDM. Overall knowledge of DM was poor. Public
      health programmes should target those of low socioeconomic status and aim to
      increase knowledge of DM in rural Bangladesh.

PMID- 25851831
TI  - Synthesis, characterization and gas sensing properties of novel homo and hetero
      dinuclear ball-type phthalocyanines.
AB  - New ball-type homodinuclear Co(ii)-Co(ii) phthalocyanine () and ball-type
      heterodinuclear Co(ii)-Fe(ii) phthalocyanine () were synthesized from the
      corresponding [2,10,16,24-tetrakis{4,4'-cyclohexylidenebis(2
      cyclohexyphenoxyphthalonitrile)}phthalocyaninatocobalt(ii)] (). The novel
      compounds have been characterized by elemental analysis, IR, UV-Vis and MALDI-TOF
      mass spectroscopy. Gas sensing capability of the spin coated film of and were
      studied using amperometric technique at various temperatures. For a better
      understanding of the interaction of and films with organic compounds, two
      different groups of compounds (aromatics and alcohols) were selected as test
      analytes. It was observed that the operating temperature had a considerable
      effect on the gas sensing performance of the sensors investigated. The
      experimental results show that film offers a promising perspective as a sensing
      material for the detection of relatively low aromatic vapours even at room
      temperature. This suggests that aromatics might be distinguished from alcohols.
      The obtained data were analysed using two different adsorption kinetic models:
      the pseudo first order equation and Elovich equation to determine the best fit
      equation for the adsorption of toluene vapor onto and films. The first-order
      equation was the best of the various kinetic models studied to describe the
      adsorption kinetic of toluene on Pc films at higher concentrations, as evidenced
      by the highest correlation coefficients. In addition, it was observed that
      Elovich equation generates a straight line that best fit to the data of
      adsorption of lower concentrations of toluene. 

PMID- 25851832
TI  - Surface-based chondroblastoma of the tibia: a unique presentation.
AB  - BACKGROUND: Chondroblastoma is a benign tumor classically located within the
      epiphysis of the long bones. The tumor is believed to arise from immature cells
      of the epiphyseal plate. Purely metaphyseal or diaphyseal chondroblastoma is
      exceedingly uncommon, occurring in approximately 2% of chondroblastoma cases. In
      all of these non-epiphyseal-based cases, the tumor has been intramedullary.
      METHODS: We describe the histologic and imaging features of the first detailed
      description of a surface-based chondroblastoma. RESULTS: The tumor was located in
      the anteromedial midshaft of the tibia in a 47-year-old male. CONCLUSION: We
      discuss the diagnostic considerations and possible etiology of chondroblastoma
      given this unusual location.

PMID- 25851834
TI  - Antifeedant activity of xanthohumol and supercritical carbon dioxide extract of
      spent hops against stored product pests.
AB  - Xanthohumol, a prenylated flavonoid from hops, and a supercritical carbon dioxide
      extract of spent hops were studied for their antifeedant activity against stored
      product insect pests: Sitophilus granarius L., Tribolium confusum Duv. and
      Trogoderma granarium Everts. Xanthohumol exhibited medium deterrent activity
      against the adults of S. granarius L. and larvae of T. confusum Duv. The spent
      hops extract was more active than xanthohumol towards the adults of T. confusum
      Duv. The potential application of the crude spent hops extract as a feeding
      deterrent against the stored product pests is proposed. 

PMID- 25851837
TI  - The development of modern approaches to aphasia: a concise overview.
AB  - The aim of this article is to review the rationale on which modern aphasia test
      batteries are based. Since the mid-1950s, a starting point chosen because the
      discipline of speech (language) pathology was created during that period, a
      corpus of English aphasia tests was identified through searches of electronic
      databases. The tests were critically evaluated in terms of their theoretical
      roots and influences. During the past 50 years, the fundamentals of aphasia
      assessment remained basically unchanged, that is, to identify and gain insight
      into the nature and the degree of a language disturbance. However, the way in
      which the assessment has taken place has shifted back and forth from a purely
      medical approach to a more neurolinguistic or social approach depending on the
      influence exerted by different scientific fields. Not a single model on which
      aphasia assessments rely covers the many and multifaceted problems of individuals
      with aphasia. At several points in time during the rehabilitation process, the
      clinician and the patient will encounter a crossroad, where it has to be decided
      which path to follow next and how to evaluate the covered path. Besides
      application of formal test batteries, observations in different natural settings,
      evaluations of functional communication and insights into psychosocial coping
      contribute towards a holistic approach to aphasia. 

PMID- 25851835
TI  - Lentibacillus garicola sp. nov., isolated from myeolchi-aekjeot, a Korean
      fermented anchovy sauce.
AB  - A Gram-stain positive, aerobic and moderately halophilic bacterium, designated
      strain SL-MJ1(T), was isolated from myeolchi-aekjeot, a Korean traditionally
      fermented anchovy sauce. Cells were observed to be non-spore-forming rods showing
      oxidase-negative and catalase-positive reactions. Growth of strain SL-MJ1(T) was
      observed at 15-40  degrees C (optimum, 30  degrees C) and pH 6.5-8.0 (optimum, pH
      7.0) and in the presence of 0-20 % (w/v) NaCl (optimum, 6 %). Chemotaxonomic data
      (major isoprenoid quinone: menaquinone-7; DNA G + C content: 42.8 mol%; cell wall
      type: meso-diaminopimelic acid; major fatty acids: anteiso-C15:0, anteiso-C17:0
      and iso-C16:0) support the affiliation of the isolate to the genus Lentibacillus.
      Phosphatidylglycerol, diphosphatidylglycerol and an unidentified phospholipid
      were identified as the major cellular polar lipids. Comparative 16S rRNA gene
      sequence analysis showed that strain SL-MJ1(T) is most closely related to
      Lentibacillus juripiscarius IS40-3(T) with a 95.3 % similarity. Phylogenetic
      analysis based on 16S rRNA gene sequences also support the conclusion that strain
      SL-MJ1(T) forms a phylogenetic lineage with members of the genus Lentibacillus
      within the family Bacillaceae. Given its phylogenetic, phenotypic and
      chemotaxonomic features, we conclude that strain SL-MJ1(T) represents a novel
      species of the genus Lentibacillus, for which the name Lentibacillus garicola sp.
      nov. is proposed. The type strain is SL-MJ1(T) (=KACC 18130(T) = JCM 30131(T)). 

PMID- 25851838
TI  - Development and validity of the Outdoor Falls Questionnaire.
AB  - The aim of this study was to develop and examine the content and face validity of
      the Outdoor Falls Questionnaire. The initial questionnaire was developed by the
      primary investigator on the basis of the existing literature on outdoor falls. A
      rating scale was used to obtain feedback from content experts to ascertain the
      validity of each question and the questionnaire as a whole. Cognitive
      interviewing of community-dwelling seniors was performed to ensure accurate
      interpretation of each question. An expert in questionnaire design reviewed the
      questions for language and structure. Content experts rated the questionnaire as
      a whole as 'quite relevant' or 'very relevant' to outdoor falls. The majority of
      individual questions (22 of 32) were rated by experts as either quite relevant or
      very relevant. Feedback from reviewers and older adults on specific questions
      were incorporated into the revised questionnaire. Preliminary testing
      demonstrates that the Outdoor Falls Questionnaire has good content and face
      validity. Further testing is needed to examine factor structure, to establish
      reliability, internal consistency, and interclass correlations. 

PMID- 25851836
TI  - Sporadic Creutzfeldt-Jakob Disease MM1+2C and MM1 are Identical in Transmission
      Properties.
AB  - The genotype (methionine, M or valine, V) at polymorphic codon 129 of the PRNP
      gene and the type (1 or 2) of abnormal prion protein in the brain are the major
      determinants of the clinicopathological features of sporadic Creutzfeldt-Jakob
      disease (CJD), thus providing molecular basis for classification of sporadic CJD,
      that is, MM1, MM2, MV1, MV2, VV1 or VV2. In addition to these "pure" cases,
      "mixed" cases presenting mixed neuropathological and biochemical features have
      also been recognized. The most frequently observed mixed form is the co
      occurrence of MM1 and MM2, namely MM1+2. However, it has remained elusive whether
      MM1+2 could be a causative origin of dura mater graft-associated CJD (dCJD), one
      of the largest subgroups of iatrogenic CJD. To test this possibility, we
      performed transmission experiments of MM1+2 prions and a systematic
      neuropathological examination of dCJD patients in the present study. The
      transmission properties of the MM1+2 prions were identical to those of MM1 prions
      because MM2 prions lacked transmissibility. In addition, the neuropathological
      characteristics of MM2 were totally absent in dCJD patients examined. These
      results suggest that MM1+2 can be a causative origin of dCJD and causes
      neuropathological phenotype similar to that of MM1. 

PMID- 25851839
TI  - Synergism of antioxidant action of vitamins E, C and quercetin is related to
      formation of molecular associations in biomembranes.
AB  - Vitamins E, C and polyphenols (flavonoids and non-flavonoids) are major natural
      antioxidants capable of preventing damage generated by oxidative stress. Here we
      show the capacity of these antioxidants to form non-covalent association within
      lipid bilayers close to the membrane/cytosol interface. Antioxidant regeneration
      is significantly enhanced in these complexes. 

PMID- 25851840
TI  - Does albuminuria correlate with silent myocardial ischemia and delayed heart rate
      recovery in hypertensive men without diabetes mellitus.
AB  - BACKGROUND: In diabetes patients, albuminuria has been proven to be an
      independent predictor for SMI and delayed heart rate recovery (HRR). However, in
      hypertensive patients without diabetes the correlation is still unclear. AIM: To
      determine the correlation between albuminuria to SMI and delayed HRR in
      hypertensive patients without diabetes. METHODS: Fourty consecutive asymptomatic
      primary hypertensive men, aged 40-60 years, without diabetes were included. They
      underwent treadmill stress testing (TST) and collection of spot urine to measure
      albumin urine to creatinine ratio (ACR). SMI and HRR at first, second, and third
      minute were then recorded. SMI was diagnosed if positive ischemic criteria of TST
      was met without anginal symptom. Albuminuria and delayed HRR were diagnosed based
      on the treshold value respectively. RESULTS: SMI was diagnosed in 15 % patients.
      The prevalence of delayed HRR at the first-, second-, and third-minute after
      exercise were 60, 80, and 52.5 % respectively. Albuminuria was significantly
      associated with SMI [OR 13.889 (95 % CI 1.423-135.544), p = 0.014]. ROC curve
      analysis demonstrated the area under the curve (AUC) = 0.784 [(95 % CI 0.588
      0.98), p = 0.028], with subsequent calculated sensitivity, specificity, positive-
      and negative-predictive value of albuminuria to predict SMI were 83.3, 73.5,
      35.7, and 96.2 % respectively. Those were no significant correlation between
      albuminuria and delayed HRR at first, second, and third minute. CONCLUSION:
      Albuminuria is a potential marker for excluding SMI in asymptomatic hypertensive
      men without diabetes.

PMID- 25851842
TI  - Efficacy of communication skills training on colorectal cancer screening by GPs:
      a cluster randomised controlled trial.
AB  - Colorectal cancer (CRC) mass screening has been implemented in France since 2008.
      Participation rates remain too low. The objective of this study was to test if
      the implementation of a training course focused on communication skills among
      general practitioners (GP) would increase the delivery of gaiac faecal occult
      blood test and CRC screening participation among the target population of each
      participating GP. A cluster randomised controlled trial was conducted with GP's
      practice as a cluster unit. GPs from practices in the control group were asked to
      continue their usual care. GPs of the intervention group received a 4-h
      educational training, built with previous qualitative data on CRC screening
      focusing on doctor-patient communication with a follow-up of 7 months for both
      groups. The primary outcome measure was the patients' participation rate in the
      target population for each GP. Seventeen GPs (16 practices) in intervention group
      and 28 GPs (19 practices) in control group participated. The patients'
      participation rate in the intervention group were 36.7% vs. 24.5% in the control
      group (P = 0.03). Doctor-patient communication should be developed and appear to
      be one of the possible targets of improvement patients adherence and
      participation rate in the target population for CRC mass screening.

PMID- 25851843
TI  - Psychometric properties of the Musculoskeletal Function Assessment and the Short
      Musculoskeletal Function Assessment: a systematic review.
AB  - OBJECTIVES: To investigate the psychometric properties of the Musculoskeletal
      Function Assessment (MFA) and Short Musculoskeletal Function Assessment (SMFA).
      DATA SOURCES: A systematic search of the following databases was undertaken
      concerning psychometric evidence of the MFA and SMFA: PubMed, Embase, Scopus and
      Cinahl. References of retrieved articles were inspected for additional data.
      REVIEW METHOD: Articles evaluating the validity, reliability or responsiveness of
      the MFA or SMFA in patients with musculoskeletal disorders were included in this
      systematic review. The methodological quality of included articles was critically
      appraised and the psychometric data were extracted using standardized forms. An
      established set of criteria were used to synthetize the evidence in order to
      highlight the strengths and weaknesses of included questionnaires and the gaps in
      the literature. RESULTS: Nine articles on MFA and 24 articles on SMFA met the
      inclusion criteria. The SMFA fulfilled 75% of the psychometric criteria analyzed,
      while the MFA fulfilled only 50%. MFA and SMFA have excellent content validity
      and relative reliability (weighted average intraclass correlation coefficient ?
      0.87), and are moderately to highly responsive (standardized response mean
      between 0.65 and 1.13). Absolute reliability and clinically important difference
      of both questionnaires need to be defined, while the construct validity of MFA
      still needs to be established. CONCLUSION: MFA and SMFA are reliable and
      responsive tools for monitoring the function of patients with various
      musculoskeletal disorders. Still, research is needed to justify their usage in a
      clinical setting.

PMID- 25851844
TI  - Find-A-Code: how accurate is the international classification of diseases coding
      system for aplastic anemia?

PMID- 25851845
TI  - Fetal malposition: impact and management.
AB  - Fetal malposition, either occiput posterior or transverse (OT), leads to greater
      risk of cesarean delivery, prolonged labor, and increased perinatal morbidity.
      Historically, there is a known association between epidural use and malposition
      that was assumed to be due to the increased discomfort of laboring with a fetus
      in the occiput posterior position. However, evidence now suggests that the
      epidural itself may contribute to fetal malposition by impacting the probability
      of internal rotation. Fetal malposition may be impacted by manual rotation.
      Manual rotation has been associated with greater rates of delivering in the
      occiput anterior position and lower rates of cesarean delivery. 

PMID- 25851846
TI  - Transition to Office-based Obstetric and Gynecologic Procedures: Safety,
      Technical, and Financial Considerations.
AB  - Office-based surgery is increasingly desired by patients and providers due to
      ease of access, overall efficiency, reimbursement, and satisfaction. The adoption
      of office-based surgery requires careful consideration of safety, efficacy, cost,
      and feasibility within a providers practice. This article reviews the currently
      available data regarding patient and provider satisfaction as well as practical
      considerations of staffing, equipment, and supplies. To aid the practitioner,
      issues of office-based anesthesia and safety with references to currently
      available national guidelines and protocols are provided. Included is a brief
      review of billing, coding, and reimbursement. Technical procedural aspects with
      information and recommendations are summarized. 

PMID- 25851847
TI  - Management of twins: vaginal or cesarean delivery?
AB  - Recent level I evidence from a single randomized-controlled trial has shown that
      there is no difference in fetal or neonatal outcomes (composite of fetal/neonatal
      death or serious neonatal morbidity) between planned cesarean delivery and
      planned vaginal delivery for twins between 32 and 38 6/7 weeks. As long as the
      presenting twin is vertex, vaginal delivery should be considered regardless of
      the presentation of the second twin. To avoid unnecessary cesarean deliveries and
      maternal morbidity, it is important to continue to train residents to perform
      obstetrics maneuvers necessary for vaginal delivery of twins such as vaginal
      breech extraction. 

PMID- 25851848
TI  - The Safe Prevention of the Primary Cesarean.

PMID- 25851849
TI  - Promise and challenges of maternal health collaboratives.
AB  - Quality-improvement collaboratives are just one of many tools used by health care
      delivery systems to address quality and safety gaps. These initiatives usually
      encompass specific aims, multidisciplinary teams, and information sharing. In the
      recent years, there has been a significant increase in the number of maternal
      health collaboratives with 31 states having a State Perinatal Quality
      Collaborative. These programs have shown promise with significant gains in the
      reduction of early elective deliveries. Further investments by stakeholders can
      help contribute the resources needed to evaluate the effectiveness and cost
      savings of maternal health collaboratives. 

PMID- 25851850
TI  - Induction of Labor and Cesarean: What is the True Relationship?
AB  - It is a commonly held belief that labor induction increases the risk of cesarean
      delivery; women who are induced are at higher risk of cesarean as compared with
      those in spontaneous labor. This comparison group is inaccurate, however, as
      women and providers cannot choose spontaneous labor as the alternative to labor
      induction. With expectant management, spontaneous labor may occur, but as
      gestation advances, pregnancy complications may occur, or women may progress
      postterm requiring induction at a later gestation. Using the proper comparison
      group, studies find that labor induction is actually associated with a small
      decreased risk of cesarean delivery. 

PMID- 25851851
TI  - Second stage of labor.
AB  - Current American College of Obstetricians and Gynecologists' definition of
      prolonged second stage diagnoses 10% to 14% of nulliparous and 3% to 3.5% of
      multiparous women as having a prolonged second stage. The progression of labor in
      modern obstetrics may have deviated from the current labor norms established in
      the 1950s, likely due to differences in obstetric population characteristics and
      variation in clinical practice. Optimal management of the second stage in women
      with and without epidural remains debatable. Although prolonged second stage is
      associated with increased risk of maternal morbidity, conflicting data exist
      regarding the duration of second stage and associated neonatal morbidity and
      mortality. 

PMID- 25851852
TI  - The association of elevated trough serum vancomycin concentrations with obesity.
AB  - BACKGROUND: Obese patients display differences in vancomycin drug disposition,
      which may complicate attainment of appropriate serum vancomycin concentrations
      (SVCs). This study was conducted to determine if obesity leads to trough SVCs
      above the therapeutic range. METHODS: This retrospective cohort study sought to
      determine the rate and predictors of high (i.e. >20 mg/L) serum trough levels
      according to level of obesity. RESULTS: Increasing BMI predicted SVCs > 20 mg/L
      after controlling for dose, age, and serum creatinine. Obese patients had
      significantly higher mean trough SVCs compared to non-obese patients (16.5 mg/L
      vs 12.1 mg/L, p = 0.004) and a significantly higher proportion of obese patients
      had trough SVCs > 20 mg/L (18.9% vs 4.2%, p = 0.03). CONCLUSION: Increasing
      obesity predicted higher probabilities of SVCs > 20 mg/L. Development of
      alternative dosing and management strategies for vancomycin may be necessary to
      account for pharmacokinetic changes associated with obesity.

PMID- 25851853
TI  - Early measurement of urinary N-acetyl-beta-glucosaminidase helps predict severe
      hyponatremia associated with cisplatin-containing chemotherapy.
AB  - BACKGROUND: Although cisplatin is a widely used anticancer drug for treating
      various types of cancer, its clinical application is limited by severe systemic
      toxicities, such as nephropathy, hematologic toxicity, and gastrointestinal
      toxicity. There are no reliable and validated biomarkers to predict adverse
      events caused by cisplatin. METHODS: Sixty-six patients who underwent cisplatin
      containing first-line chemotherapy between June 2010 and November 2013 were
      retrospectively analyzed. Data on urinary N-acetyl-beta-glucosaminidase
      activities measured 24-48 h after cisplatin infusion were retrieved, and adverse
      events during the first course of chemotherapy were recorded according to the
      Common Terminology Criteria for Adverse Events version 4.0. RESULTS: Patient
      characteristics were: male/female 60/6, median age 65 (range 36-78) years,
      esophageal/gastric/other cancer 60/4/2, chemotherapy regimen docetaxel-cisplatin
      fluorouracil/fluorouracil-cisplatin/S-1-cisplatin 54/8/4, cisplatin dose (mg/sm)
      60/70/80 16/43/7. Grade 3/4 adverse events were leukopenia (40.9%), neutropenia
      (54.4%), febrile neutropenia (37.9%), hyponatremia (28.8%), and acute kidney
      injury (37.9%). Patients with 20 units/gram creatinine or higher urinary N-acetyl
      beta-glucosaminidase developed statistically lower minimum serum sodium
      concentration (median 126 vs. 134 mEq/L, p = 0.0053). There were no significant
      correlations between urinary N-acetyl-beta-glucosaminidase and the development of
      other severe adverse events. CONCLUSION: Early significant increase in urinary N
      acetyl-beta-glucosaminidase predicts subsequent development of severe
      hyponatremia after cisplatin-containing chemotherapy.

PMID- 25851854
TI  - Emotional symptoms among adolescents: epidemiological analysis of individual-,
      classroom- and school-level factors.
AB  - BACKGROUND: Large proportions of schoolchildren suffer from emotional symptoms
      and there are large variations across schools. It is unknown to what degree this
      variation is due to composition of schoolchildren in each school or to contextual
      factors. Objectives are to identify factors at individual, classroom and school
      levels associated with emotional symptoms. METHOD: Data stem from the Danish
      contribution to the international Health Behaviour in School-aged Children study
      2010 including 4922 schoolchildren aged 11-15-years from a random sample of
      schools and including data from school leaders. Emotional symptoms are defined as
      daily presence of at least one of four symptoms: feeling low, irritable or bad
      tempered, nervous and having difficulties falling asleep. Multilevel
      multivariable logistic regression analyses are applied to identify and quantify
      factors at individual, classroom and school level. RESULTS: Schoolchildren from
      low (odds ratio (OR) 1.70, 95% CI: 1.33-2.17) and medium (OR 1.50, 95% CI: 1.22
      1.85) occupational social class (OSC), girls (OR 1.32, 95% CI: 1.13-1.56) and
      schoolchildren exposed to bullying (OR 3.82, 95% CI: 2.71-5.40), had increased
      odds for emotional symptoms. A negative classroom climate was associated with
      emotional symptoms (OR 1.29, 95% CI: 0.99-1.69) and so was being part of
      classrooms with a high prevalence of bullying (OR 1.28, 95% CI: 1.0-1.60).
      CONCLUSION: Female sex, low OSC, single parent family, exposure to bullying and a
      high prevalence of bullying within a class are all associated with emotional
      symptoms. Most variation across schools is explained by individual-level factors
      but psychosocial aspects of the classroom environment also play a role.

PMID- 25851856
TI  - Targeting backup DNA repair in cancer.
AB  - New research shows that DNA polymerase theta is a key player in PARP-mediated DNA
      damage repair and essential for the survival of cancer cells where homologous
      recombination is compromised. Poltheta could be a biomarker for PARP-inhibitor
      response, and is a potential therapeutic target for overcoming resistance to
      these drugs. 

PMID- 25851857
TI  - Philanthropies team up to fund young scientists.
AB  - The Howard Hughes Medical Institute, the Bill & Melinda Gates Foundation, and the
      Simons Foundation announced an initiative to support talented, early-career
      scientists working in biology and biomedical research. They plan to invest $148
      million in the program over the next 5 years. 

PMID- 25851858
TI  - Breast cancer susceptibility genes pile up.
AB  - A large genome-wide association analysis has revealed 15 more SNPs associated
      with breast cancer, which could provide additional genetic markers for risk
      analysis. 

PMID- 25851859
TI  - Dinutuximab approved for high-risk neuroblastoma.
AB  - The FDA approved the use of dinutuximab, in combination with three other agents,
      for high-risk neuroblastoma, offering patients the first major new treatment in
      more than a decade. 

PMID- 25851860
TI  - Accurate evaluation of relationships among serum lipoprotein lipase mass,
      visceral fat and retinal nerve fiber layer thickness.

PMID- 25851861
TI  - Accurate evaluation of relationships among serum lipoprotein lipase mass,
      visceral fat, and retinal nerve fiber layer thickness.

PMID- 25851862
TI  - Vascular endothelial growth factor plasma levels before and after treatment of
      retinopathy of prematurity with ranibizumab.
AB  - PURPOSE: To evaluate vascular endothelial growth factor (VEGF) plasma levels
      before and after intravitreal injection of ranibizumab in patients with
      retinopathy of prematurity (ROP). METHODS: Case series study. Eleven infants with
      type 1 pre-threshold ROP were treated with intravitreal ranibizumab 0.5 mg. Blood
      samples were collected before intravitreal injection of ranibizumab and 1 day, 1
      week, 2 weeks, and 4 weeks after injection. Concentration of plasma VEGF was
      measured by enzyme-linked immunosorbent assays (ELISA). RESULTS: The mean +/-
      standard deviation of plasma VEGF concentration of the available samples before
      and 1 day, 1 week, 2 weeks, and 4 weeks after a total of 0.5 mg ranibizumab
      injection were 46.07 +/- 9.40 pg/ml (n = 11), 10.59 +/- 7.32 pg/ml (n = 5), 45.76
      +/- 6.75 pg/ml (n = 5), 62.44 +/- 15.51 pg/ml (n = 5), and 56.82 +/- 12.78 pg/ml
      (n = 4) respectively. A significant reduction was found in the plasma VEGF levels
      1 day after intravitreal injection of ranibizumab (P = 0.002). No significant
      differences were found between before and 1 week, 2 weeks, and 4 weeks after the
      injection. CONCLUSIONS: Intravitreal ranibizumab reduced plasma VEGF levels 1 day
      after injection in infants with ROP. This effect disappeared 1 week after the
      injection. Intravitreal ranibizumab did not induce prolonged systemic VEGF
      suppression.

PMID- 25851863
TI  - Comment on: Park SW, Byon IS, Kim HY, Lee JE, Oum BS (2015) Analysis of the
      ganglion cell layer and photoreceptor layer using optical coherence tomography
      after idiopathic epiretinal membrane surgery. Graefes Arch Clin Exp Ophthalmol
      253:207-14.

PMID- 25851864
TI  - Erratum to: Effect of gravity in long-term vitreous tamponade: in vivo
      investigation using perfluorocarbon liquids and semi-fluorinated alkanes.

PMID- 25851865
TI  - Maternal and neonatal outcomes after implementation of a hospital policy to limit
      low-risk planned caesarean deliveries before 39 weeks of gestation: an
      interrupted time-series analysis.
AB  - OBJECTIVE: To evaluate the extent to which implementing a hospital policy to
      limit planned caesarean deliveries before 39 weeks of gestation improved neonatal
      health, maternal health, and healthcare costs. DESIGN: Retrospective cohort
      study. SETTING: British Columbia Women's Hospital, Vancouver, Canada, in the
      period 2005-2012. POPULATION: Women with a low-risk planned repeat caesarean
      delivery. METHODS: An interrupted time series design was used to evaluate the
      policy to limit planned caesarean deliveries before 39 weeks of gestation,
      introduced on 1 April 2008. MAIN OUTCOME MEASURES: Composite adverse neonatal
      health outcome (respiratory morbidity, 5-minute Apgar score of <7, neonatal
      intensive care unit admission, mortality), postpartum haemorrhage, obstetrical
      wound infection, out-of-hour deliveries, length of stay, and healthcare costs.
      RESULTS: Between 2005 and 2008, 60% (1204/2021) of low-risk planned caesarean
      deliveries were performed before 39 weeks of gestation. After the introduction of
      the policy, the proportion of planned caesareans dropped by 20 percentage points
      (adjusted risk difference of 20 fewer cases per 100 deliveries; 95% CI -25.8, 
      14.3) to 41% (1033/2518). The policy had no detectable impact on adverse neonatal
      outcomes (2.2 excess cases per 100; 95% CI -0.4, 4.8), maternal complications, or
      healthcare costs, but increased the risk of out-of-hours delivery from 16.2 to
      21.1% (adjusted risk difference 6.3 per 100; 95% CI 1.6, 10.9). CONCLUSIONS: We
      found little evidence that a hospital policy to limit planned caesareans before
      39 weeks of gestation reduced adverse neonatal outcomes. Hospital administrators
      intending to introduce such policies should anticipate, and plan for, modest
      increases in out-of-hours and emergency-timing.

PMID- 25851866
TI  - Review insights into the interactions of amino acids and peptides with inorganic
      materials using single molecule force spectroscopy.
AB  - Understanding the interactions between proteins and inorganic surfaces is
      important for the development of new biomaterials and implants as they interface
      with the immune response by proteins. In addition, the adsorption of proteins to
      inorganic surfaces leads to the formation of a conditioning layer that
      facilitates bacterial attachments and biofilm formation. As biofilm provides
      bacterial resistance to antibiotics, biofilm formation is an undesirable process
      that could be prevented by resisting protein interactions with the substrate.
      Moreover, the interaction between proteins and inorganic materials is the basis
      for the formation of composite materials in nature. Understanding the underlying
      forces that governs these interactions would lead to the design of new and unique
      composite materials in vitro. This review focuses on the insights gained using
      single-molecule force spectroscopy by AFM on these interactions. This tool
      provides molecular information, at the single molecule level, on the interaction
      between a molecule on the AFM tip and a substrate.

PMID- 25851889
TI  - Neuromuscular ultrasound of cranial nerves.
AB  - Ultrasound of cranial nerves is a novel subdomain of neuromuscular ultrasound
      (NMUS) which may provide additional value in the assessment of cranial nerves in
      different neuromuscular disorders. Whilst NMUS of peripheral nerves has been
      studied, NMUS of cranial nerves is considered in its initial stage of research,
      thus, there is a need to summarize the research results achieved to date.
      Detailed scanning protocols, which assist in mastery of the techniques, are
      briefly mentioned in the few reference textbooks available in the field. This
      review article focuses on ultrasound scanning techniques of the 4 accessible
      cranial nerves: optic, facial, vagus and spinal accessory nerves. The relevant
      literatures and potential future applications are discussed. 

PMID- 25851890
TI  - Chasing tics in the human brain: development of open, scheduled and closed loop
      responsive approaches to deep brain stimulation for tourette syndrome.
AB  - Tourette syndrome is a childhood-onset disorder characterized by a combination of
      motor and vocal tics, often associated with psychiatric comorbidities including
      attention deficit and hyperactivity disorder and obsessive-compulsive disorder.
      Despite an onset early in life, half of patients may present symptoms in
      adulthood, with variable degrees of severity. In select cases, the syndrome may
      lead to significant physical and social impairment, and a worrisome risk for self
      injury. Evolving research has provided evidence supporting the idea that the
      pathophysiology of Tourette syndrome is directly related to a disrupted circuit
      involving the cortex and subcortical structures, including the basal ganglia,
      nucleus accumbens, and the amygdala. There has also been a notion that a
      dysfunctional group of neurons in the putamen contributes to an abnormal
      facilitation of competing motor responses in basal ganglia structures ultimately
      underpinning the generation of tics. Surgical therapies for Tourette syndrome
      have been reserved for a small group of patients not responding to behavioral and
      pharmacological therapies, and these therapies have been directed at modulating
      the underlying pathophysiology. Lesion therapy as well as deep brain stimulation
      has been observed to suppress tics in at least some of these cases. In this
      article, we will review the clinical aspects of Tourette syndrome, as well as the
      evolution of surgical approaches and we will discuss the evidence and clinical
      responses to deep brain stimulation in various brain targets. We will also
      discuss ongoing research and future directions as well as approaches for open,
      scheduled and closed loop feedback-driven electrical stimulation for the
      treatment of Tourette syndrome. 

PMID- 25851891
TI  - A consensus in Korea regarding a protocol to reduce preanalytical sources of
      variability in the measurement of the cerebrospinal fluid biomarkers of
      Alzheimer's disease.
AB  - Cerebrospinal fluid (CSF) can provide vital informative about pathological
      processes occurring in the brain. In particular, the CSF concentrations of
      Abeta42, tTau, and pTau181 are useful for the early diagnosis of Alzheimer's
      disease (AD). However, many studies have demonstrated that confounding factors
      related to the preanalytical processing of CSF can seriously influence
      measurements of these AD biomarkers. It is therefore important to develop a
      standardized protocol for the acquisition and handling of CSF, particularly with
      regard to the types of tube used for collection and storage, the proper aliquot
      volume, blood contamination, and the number of tube transfers and freeze-thaw
      cycles, because these aspects of the procedure have been shown to affect AD
      biomarker measurements. A survey of the impact of several individual
      preanalytical procedures on the measurement of AD biomarkers in CSF was conducted
      for this review article, and the implications of the differences among them are
      discussed. Furthermore, following a review of the procedures used in Korean and
      international biomarker laboratories, a consensus was reached among a cooperative
      Korean multicenter research group regarding a standardized protocol for the
      analysis of AD biomarkers in CSF. All efforts were made to be stringent regarding
      the controversial issues associated with this protocol, thus minimizing the
      confounding influence of various factors on current investigations using
      established AD biomarkers and on future studies using novel biomarkers of AD and
      other neurodegenerative disorders. 

PMID- 25851892
TI  - Feasibility of using a mobile application for the monitoring and management of
      stroke-associated risk factors.
AB  - BACKGROUND AND PURPOSE: Recent advances in information technology have created
      opportunities for advances in the management of stroke. The objective of this
      study was to test the feasibility of using a smartphone software application
      (app) for the management of vascular risk factors in patients with stroke.
      METHODS: This prospective clinical trial developed a smartphone app, the 'Korea
      University Health Monitoring System for Stroke: KUHMS2,' for use by patients with
      stroke. During a 6-month follow-up period, its feasibility was assessed by
      measuring the changes in their vascular risk-factor profiles and the number of
      days per patient with data registration into the app. The effect of the app on
      the achievement rate of risk-factor targets was assessed by classifying subjects
      into compliant and noncompliant groups. RESULTS: At the end of the trial, data on
      48 patients were analyzed. The number of days on which data were registered into
      the app was 60.42+/-50.17 (mean+/-standard deviation). Among predefined vascular
      risk factors, the target achievement rate for blood pressure and glycated
      hemoglobin (Hb(A1c)) improved significantly from baseline to the final
      measurement. The serial changes in achievement rates for risk-factor targets did
      not differ between the compliant and noncompliant groups. CONCLUSIONS: Many
      challenges must be overcome before mobile apps can be used for patients with
      stroke. Nevertheless, the app tested in this study induced a shift in the risk
      profiles in a favorable direction among the included stroke patients.

PMID- 25851893
TI  - Effect of carotid artery stenting on cognitive function in patients with carotid
      artery stenosis: a prospective, 3-month-follow-up study.
AB  - BACKGROUND AND PURPOSE: Carotid artery stenting (CAS) is emerging as an
      alternative to carotid endarterectomy for the treatment of carotid artery
      stenosis (CS), but the effect of CAS on the cognitive function of patients with
      severe CS has not been fully investigated. The aim of this study was to use
      comprehensive neuropsychological tests to determine the effect of CAS on
      cognitive function from baseline to 3 months postprocedure in patients with
      severe CS. METHODS: Thirty-one patients due to undergo CAS due to high-grade CS
      (>=70%) and 11 control subjects who were diagnosed with CS, but who did not
      undergo CAS, and who visited the clinic or emergency room between February 2009
      and February 2012 were recruited consecutively at baseline (i.e., pre-CAS).
      Follow-up neuropsychological evaluations after 3 months were completed by 23 of
      the 31 patients who underwent CAS, and by 10 of the 11 control subjects. The
      primary cognitive outcome was assessed using a neuropsychological test containing
      subcategories designed to test general cognitive function, attention,
      visuospatial function, language and related functions, memory, and frontal
      lobe/executive function. RESULTS: Of the 23 patients undergoing CAS who completed
      the 3-month follow-up tests, 12 had asymptomatic CS. During the 3-month follow-up
      period, the patients who underwent CAS and those with asymptomatic CS achieved
      similar results to the control group on all cognitive tests. However, symptomatic
      CS patients (n=11) who underwent CAS exhibited improvements in visuospatial
      function (p=0.046) and total Seoul Neuropsychological Screening Battery-Dementia
      Version scores (p=0.010) in comparison with both the asymptomatic CS patients and
      the control group. CONCLUSIONS: The findings of this study suggest that CAS has a
      positive effect on cognitive function in patients with symptomatic CS over a 3
      month follow-up period. A long-term, multicenter, prospective case-control study
      would be helpful to predict quality of life and prognoses for patients undergoing
      CAS.

PMID- 25851894
TI  - The Persian Version of a Participation Scale: Is It Valid and Reliable Enough for
      Use among Iranian Patients with Multiple Sclerosis?
AB  - BACKGROUND AND PURPOSE: The aim of this study was to determine the face and
      criterion validity, stability reliability, and internal consistency of the
      Persian version of the Impact on Participation and Autonomy (IPA-p) scale among
      Iranian people with multiple sclerosis (MS). METHODS: Trained experts interviewed
      364 MS patients and their relatives to assess the criterion validity, stability
      reliability, and internal consistency of the IPA-p scale. Ten specialists from
      different disciplines were also recruited to assess its face validity. A consent
      form was completed by the patients and their relatives. Internal consistency
      reliability was measured using Cronbach's alpha and stability reliability was
      assessed using interclass correlation coefficients (ICCs). The test-retest method
      was used to detect the reliability of the questioner. The study subjects
      completed the IPA-p scale on two occasions separated by an interval of 30-45
      days. Study checklists were also used to assess the face validity, stability
      reliability, and internal consistency of the IPA-p scale. RESULTS: About 50% of
      the respondents reported their perceived overall participation to be "good" or
      "very good" and 60% of the specialists rated the ability of the IPA-p scale to
      measure what it was designed for as "excellent." Spearman correlation
      coefficients were >0.8 for all but one IPA-p domain. Cronbach's alpha between the
      mean IPA-p scale scores achieved on two separate occasions ranged from 0.858 to
      0.913. The highest and lowest internal consistencies belonged to the "social
      relationships" and "education and learning" domains, respectively. The test
      retest ICCs for the nine domains were between 0.789 and 0.919, and all were
      significant at p<0.001. CONCLUSIONS: The IPA-p questionnaire can be considered a
      valid and reliable instrument for assessing self-reported participation among
      Iranian MS patients.

PMID- 25851895
TI  - Granulocyte colony-stimulating factor for amyotrophic lateral sclerosis: a
      randomized, double-blind, placebo-controlled study of Iranian patients.
AB  - BACKGROUND AND PURPOSE: The aim of this study was to determine the efficacy and
      tolerability of granulocyte colony-stimulating factor (G-CSF) in subjects with
      amyotrophic lateral sclerosis (ALS). METHODS: Forty subjects with ALS were
      randomly assigned to two groups, which received either subcutaneous G-CSF (5
      MUg/kg/q12h) or placebo for 5 days. The subjects were then followed up for 3
      months using the ALS Functional Rating Scale-Revised (ALSFRS-R), manual muscle
      testing, ALS Assessment Questionnaire-40, and nerve conduction studies.
      CD34+/CD133+ cell count and monocyte chemoattractant protein-1 (MCP-1) levels
      were evaluated at baseline. RESULTS: The rate of disease progression did not
      differ significantly between the two groups. The reduction in ALSFRS-R scores was
      greater in female subjects in the G-CSF group than in their counterparts in the
      placebo group. There was a trend toward a positive correlation between baseline
      CSF MCP-1 levels and the change in ALSFRS-R scores in both groups (Spearman's
      rho=0.370, p=0.070). CONCLUSIONS: With the protocol implemented in this study, G
      CSF is not a promising option for the treatment of ALS. Furthermore, it may
      accelerate disease progression in females.

PMID- 25851896
TI  - Preclinical assessment of the anticancer drug response of plexiform neurofibroma
      tissue using primary cultures.
AB  - BACKGROUND AND PURPOSE: Individualized drug testing for tumors using a strategy
      analogous to antibiotic tests for infectious diseases would be highly desirable
      for personalized and individualized cancer care. METHODS: Primary cultures
      containing tumor and nontumor stromal cells were utilized in a novel strategy to
      test drug responses with respect to both efficacy and specificity. The strategy
      tested in this pilot study was implemented using four primary cultures derived
      from plexiform neurofibromas. Responses to two cytotoxic drugs (nilotinib and
      imatinib) were measured by following dose-dependent changes in the proportions of
      tumor and nontumor cells, determined by staining them with cell-type-specific
      antibodies. The viability of the cultured cells and the cytotoxic effect of the
      drugs were also measured using proliferation and cytotoxicity assays. RESULTS:
      The total number of cells decreased after the drug treatment, in accordance with
      the observed reduction in proliferation and increased cytotoxic effect upon
      incubation with the two anticancer drugs. The proportions of Schwann cells and
      fibroblasts changed dose-dependently, although the patterns of change varied
      between the tumor samples (from different sources) and between the two drugs. The
      highly variable in vitro drug responses probably reflect the large variations in
      the responses of tumors to therapies between individual patients in vivo.
      CONCLUSIONS: These preliminary results suggest that the concept of assessing in
      vitro drug responses using primary cultures is feasible, but demands the
      extensive further development of an application for preclinical drug selection
      and drug discovery.

PMID- 25851897
TI  - The usefulness of proximal radial motor conduction in acute compressive radial
      neuropathy.
AB  - BACKGROUND AND PURPOSE: The objective of this study was to determine diagnostic
      and prognostic values of proximal radial motor conduction in acute compressive
      radial neuropathy. METHODS: Thirty-nine consecutive cases of acute compressive
      radial neuropathy with radial conduction studies-including stimulation at Erb's
      point-performed within 14 days from clinical onset were reviewed. The radial
      conduction data of 39 control subjects were used as reference data. RESULTS:
      Thirty-one men and eight women (age, 45.2+/-12.7 years, mean+/-SD) were enrolled.
      All 33 patients in whom clinical follow-up data were available experienced
      complete recovery, with a recovery time of 46.8+/-34.3 days. Partial conduction
      block was found frequently (17 patients) on radial conduction studies. The
      decrease in the compound muscle action potential area between the arm and Erb's
      point was an independent predictor for recovery time. CONCLUSIONS: Proximal
      radial motor conduction appears to be a useful method for the early detection and
      prediction of prognosis of acute compressive radial neuropathy.

PMID- 25851898
TI  - PEX7 Mutations Cause Congenital Cataract Retinopathy and Late-Onset Ataxia and
      Cognitive Impairment: Report of Two Siblings and Review of the Literature.

PMID- 25851899
TI  - Utility of oblique coronal images in elderly and cognitively impaired patients.

PMID- 25851900
TI  - Reconsidering the detection of tolerance to individualize immunosuppression
      minimization and to improve long-term kidney graft outcomes.
AB  - In kidney transplantation, minimizing the side effects of the immunosuppressive
      regimen and inducing tolerance to allograft are the two main objectives to
      improve outcome. At present, these objectives are far from being achieved and
      remain elusive for the majority of transplant recipients. Rejection rate and
      mortality on the long term are still unacceptable. There is thus a pressing need
      to improve this situation. Therefore, some spontaneously tolerant kidney
      recipients are described in clinics, and recent advances in immunological and
      molecular techniques have led to a resurgence of interest in studying those rare
      transplanted recipients through coordinated efforts from international consortia.
      Indeed, they offer, on the one hand, the possibility to develop specific
      biomarkers indicative of this state that would constitute a major advantage in
      the care of the patients allowing personalized minimization of drugs, so reducing
      related costs and side effects. On the other hand, they represent a unique model
      of study to understand the mechanisms of regulation implicated in this state that
      may help the development of inducing therapies. Recent efforts, concentrated on
      noninvasive analyses of peripheral blood, identified a predominance of several B
      cell subsets, some of which harbouring regulatory functions, and related marker
      genes. These findings, validated in independent multicentric cohorts, led
      credence to an unsuspected role for the B-cell compartment in tolerance to kidney
      allograft. The identification of patients, harbouring these markers, among
      immunosuppressed recipients with stable graft function and the existence of drugs
      with selective effect on B cell pave the way for the possibility to improve long
      term graft outcomes. Therefore, before routine application, these findings need
      to be confirmed in large prospective studies in the context of planned reduced
      immunosuppression. 

PMID- 25851901
TI  - Methylosome Protein 50 and PKCdelta/p38delta Protein Signaling Control
      Keratinocyte Proliferation via Opposing Effects on p21Cip1 Gene Expression.
AB  - Protein arginine methyltransferase 5 (PRMT5) is a key epigenetic regulator that
      symmetrically dimethylates arginine residues on histones H3 and H4 to silence
      gene expression. PRMT5 is frequently observed in a complex with the cofactor
      methylosome protein 50 (MEP50), which is required for PRMT5 activity.
      PKCdelta/p38delta signaling, a key controller of keratinocyte proliferation and
      differentiation, increases p21(Cip1) expression to suppress keratinocyte
      proliferation. We now show that MEP50 enhances keratinocyte proliferation and
      survival via mechanisms that include silencing of p21(Cip1) expression. This is
      associated with enhanced PRMT5-MEP50 interaction at the p21(Cip1) promoter and
      enhanced arginine dimethylation of the promoter-associated histones H3 and H4. It
      is also associated with a MEP50-dependent reduction in the level of p53, a key
      controller of p21(Cip1) gene expression. We confirm an important biological role
      for MEP50 and PRMT5 in regulating keratinocyte proliferation using a stratified
      epidermal equivalent model that mimics in vivo epidermal keratinocyte
      differentiation. In this model, PRMT5 or MEP50 knockdown results in reduced
      keratinocyte proliferation. We further show that PKCdelta/p38delta signaling
      suppresses MEP50 expression, leading to reduced H3/H4 arginine dimethylation at
      the p21(Cip1) promoter, and that this is associated with enhanced p21(Cip1)
      expression and reduced cell proliferation. These findings describe an opposing
      action between PKCdelta/p38delta MAPK signaling and PRMT5/MEP50 epigenetic
      silencing mechanisms in regulating cell proliferation. 

PMID- 25851902
TI  - Thiobenzothiazole-modified Hydrocortisones Display Anti-inflammatory Activity
      with Reduced Impact on Islet beta-Cell Function.
AB  - Glucocorticoids signal through the glucocorticoid receptor (GR) and are
      administered clinically for a variety of situations, including inflammatory
      disorders, specific cancers, rheumatoid arthritis, and organ/tissue
      transplantation. However, glucocorticoid therapy is also associated with
      additional complications, including steroid-induced diabetes. We hypothesized
      that modification of the steroid backbone is one strategy to enhance the
      therapeutic potential of GR activation. Toward this goal, two commercially
      unavailable, thiobenzothiazole-containing derivatives of hydrocortisone (termed
      MS4 and MS6) were examined using 832/13 rat insulinoma cells as well as rodent
      and human islets. We found that MS4 had transrepression properties but lacked
      transactivation ability, whereas MS6 retained both transactivation and
      transrepression activities. In addition, MS4 and MS6 both displayed anti
      inflammatory activity. Furthermore, MS4 displayed reduced impact on islet beta
      cell function in both rodent and human islets. Similar to dexamethasone, MS6
      promoted adipocyte development in vitro, whereas MS4 did not. Moreover, neither
      MS4 nor MS6 activated the Pck1 (Pepck) gene in primary rat hepatocytes. We
      conclude that modification of the functional groups attached to the D-ring of the
      hydrocortisone steroid molecule produces compounds with altered structure
      function GR agonist activity with decreased impact on insulin secretion and
      reduced adipogenic potential but with preservation of anti-inflammatory activity.

PMID- 25851903
TI  - Essential Role for Zinc Transporter 2 (ZnT2)-mediated Zinc Transport in Mammary
      Gland Development and Function during Lactation.
AB  - The zinc transporter ZnT2 (SLC30A2) imports zinc into vesicles in secreting
      mammary epithelial cells (MECs) and is critical for zinc efflux into milk during
      lactation. Recent studies show that ZnT2 also imports zinc into mitochondria and
      is expressed in the non-lactating mammary gland and non-secreting MECs,
      highlighting the importance of ZnT2 in general mammary gland biology. In this
      study we used nulliparous and lactating ZnT2-null mice and characterized the
      consequences on mammary gland development, function during lactation, and milk
      composition. We found that ZnT2 was primarily expressed in MECs and to a limited
      extent in macrophages in the nulliparous mammary gland and loss of ZnT2 impaired
      mammary expansion during development. Secondly, we found that lactating ZnT2-null
      mice had substantial defects in mammary gland architecture and MEC function
      during secretion, including fewer, condensed and disorganized alveoli, impaired
      Stat5 activation, and unpolarized MECs. Loss of ZnT2 led to reduced milk volume
      and milk containing less protein, fat, and lactose compared with wild-type
      littermates, implicating ZnT2 in the regulation of mammary differentiation and
      optimal milk production during lactation. Together, these results demonstrate
      that ZnT2-mediated zinc transport is critical for mammary gland function,
      suggesting that defects in ZnT2 not only reduce milk zinc concentration but may
      compromise breast health and increase the risk for lactation insufficiency in
      lactating women. 

PMID- 25851904
TI  - Alteration of Electrostatic Surface Potential Enhances Affinity and Tumor Killing
      Properties of Anti-ganglioside GD2 Monoclonal Antibody hu3F8.
AB  - Ganglioside GD2 is highly expressed on neuroectodermal tumors and an attractive
      therapeutic target for antibodies that have already shown some clinical efficacy.
      To further improve the current antibodies, which have modest affinity, we sought
      to improve affinity by using a combined method of random mutagenesis and in
      silico assisted design to affinity-mature the anti-GD2 monoclonal antibody hu3F8.
      Using yeast display, mutants in the Fv with enhanced binding over the parental
      clone were FACS-sorted and cloned. In silico modeling identified the minimal key
      interacting residues involved in the important charged interactions with the
      sialic acid groups of GD2. Two mutations, D32H (L-CDR1) and E1K (L-FR1) altered
      the electrostatic surface potential of the antigen binding site, allowing for an
      increase in positive charge to enhance the interaction with the negatively
      charged GD2-pentasaccharide headgroup. Purified scFv and IgG mutant forms were
      then tested for antigen specificity by ELISA, for tissue specificity by
      immunohistochemistry, for affinity by BIACORE, for antibody-dependent cell
      mediated cytotoxicity (ADCC) and complement-mediated cytotoxicity in vitro, and
      for anti-tumor efficacy in xenografted humanized mice. The nearly 7-fold
      improvement in affinity of hu3F8 with a single D32H (L-CDR1) mutation translated
      into a ~12-fold improvement in NK92MI-transfected CD16-mediated ADCC, a 6-fold
      improvement in CD32-mediated ADCC, and a 2.5-fold improvement in complement
      mediated cytotoxicity while maintaining restricted normal tissue cross-reactivity
      and achieving substantial improvement in tumor ablation in vivo. Despite
      increasing GD2 affinity, the double mutation D32H (L-CDR1) and E1K (L-FR1) did
      not further improve anti-tumor efficacy. 

PMID- 25851905
TI  - Organization of Subunits in the Membrane Domain of the Bovine F-ATPase Revealed
      by Covalent Cross-linking.
AB  - The F-ATPase in bovine mitochondria is a membrane-bound complex of about 30
      subunits of 18 different kinds. Currently, ~85% of its structure is known. The
      enzyme has a membrane extrinsic catalytic domain, and a membrane intrinsic domain
      where the turning of the enzyme's rotor is generated from the transmembrane
      proton-motive force. The domains are linked by central and peripheral stalks. The
      central stalk and a hydrophobic ring of c-subunits in the membrane domain
      constitute the enzyme's rotor. The external surface of the catalytic domain and
      membrane subunit a are linked by the peripheral stalk, holding them static
      relative to the rotor. The membrane domain contains six additional subunits named
      ATP8, e, f, g, DAPIT (diabetes-associated protein in insulin-sensitive tissues),
      and 6.8PL (6.8-kDa proteolipid), each with a single predicted transmembrane alpha
      helix, but their orientation and topography are unknown. Mutations in ATP8
      uncouple the enzyme and interfere with its assembly, but its roles and the roles
      of the other five subunits are largely unknown. We have reacted accessible amino
      groups in the enzyme with bifunctional cross-linking agents and identified the
      linked residues. Cross-links involving the supernumerary subunits, where the
      structures are not known, show that the C terminus of ATP8 extends ~70 A from the
      membrane into the peripheral stalk and that the N termini of the other
      supernumerary subunits are on the same side of the membrane, probably in the
      mitochondrial matrix. These experiments contribute significantly toward building
      up a complete structural picture of the F-ATPase. 

PMID- 25851907
TI  - [Gender inequality in the authorship of medical articles: Analysis of Medicina
      Clinica, 1999 and 2014].

PMID- 25851906
TI  - Kruppel-like Factor 4 Promotes Esophageal Squamous Cell Carcinoma Differentiation
      by Up-regulating Keratin 13 Expression.
AB  - Squamous cell differentiation requires the coordinated activation and repression
      of genes specific to the differentiation process; disruption of this program
      accompanies malignant transformation of epithelium. The exploration of genes that
      control epidermal proliferation and terminal differentiation is vital to better
      understand esophageal carcinogenesis. KLF4 is a member of the KLF family of
      transcription factors and is involved in both cellular proliferation and
      differentiation. This study using immunohistochemistry analysis of KLF4 in
      clinical specimens of esophageal squamous cell carcinoma (ESCC) demonstrated that
      decreased KLF4 was substantially associated with poor differentiation. Moreover,
      we determined that both KLF4 and KRT13 levels were undoubtedly augmented upon
      sodium butyrate-induced ESCC differentiation and G1 phase arrest. Conversely,
      silencing of KLF4 and KRT13 abrogated the inhibition of G1-S transition induced
      by sodium butyrate. Molecular investigation demonstrated that KLF4
      transcriptionally regulated KRT13 and the expression of the two molecules
      appreciably correlated in ESCC tissues and cell lines. Collectively, these
      results suggest that KLF4 transcriptionally regulates KRT13 and is invovled in
      ESCC cell differentiation. 

PMID- 25851908
TI  - [First case of bacteremia by Sphingomonas anadarae in an patient with cancer].

PMID- 25851909
TI  - [Autoimmune endocrinopathies induced by immunomodulating antibodies in the
      treatment of cancer].

PMID- 25851910
TI  - [Follicular mycosis fungoides, a rare and aggressive variant].

PMID- 25851911
TI  - [Symmetrical polyarthritis in a patient with multicentric reticulohistiocytosis].

PMID- 25851912
TI  - [Vaccination of patients with non-Hodgkin lymphoma under rituximab or other
      immunosuppressive drugs].

PMID- 25851913
TI  - [Central neurogenic hyperventilation in a patient with post-vaccination acute
      disseminated encephalomyelitis].

PMID- 25851914
TI  - [Ocular thelaziosis, an emergent zoonosis in Spain].

PMID- 25851915
TI  - [The current role of autopsy in current clinical practice].

PMID- 25851916
TI  - A hypothesis for reactivation of pulmonary tuberculosis: How thoracic wall shape
      affects the epidemiology of tuberculosis.
AB  - This study was aimed at determining the cause for the high incidence of
      tuberculosis (TB) reactivation occurring in males with a low body mass index
      (BMI). Current thinking about pulmonary TB describes infection in the lung apex
      resulting in cavitation after reactivation. A different hypothesis is put forward
      for TB infection, suggesting that this occurs in subclinical apical cavities
      caused by increased pleural stress due to a low BMI body habitus. A finite
      element analysis (FEA) model of a lung was constructed including indentations for
      the first rib guided by paramedian sagittal CT reconstructions, and simulations
      were conducted with varying antero-posterior (AP) diameters to mimic chests with
      a different thoracic index (ratio of AP to the transverse chest diameters). A
      Pubmed search was conducted about gender and thoracic index, and the effects of
      BMI on TB. FEA modeling revealed a tenfold increase in stress levels at the lung
      apex in low BMI chests, and a four-fold increase with a low thoracic index, r(2) 
      = 0.9748 P < 0.001. Low thoracic index was related to BMI, P = 0.001. The mean
      thoracic index was statistically significantly lower in males, P = 0.001, and
      increased with age in both genders. This article is the first to suggest a
      possible mechanism linking pulmonary TB reactivation to low BMI due to the
      flattened thoracic wall shape of young male adults. The low thoracic index in
      young males may promote TB reactivation due to tissue destruction in the lung
      apex from high pleural stress levels.

PMID- 25851917
TI  - The experiences of emergency nurses in providing end-of-life care to patients in
      the emergency department.
AB  - BACKGROUND: Managing death in the emergency department is a challenge. Emergency
      nurses are expected to provide care to numerous patient groups in an often fast
      paced, life-saving environment. The purpose of this study was to describe the
      experiences of emergency nurses in providing end-of-life care, which is the care
      delivered to a patient during the time directly preceding death. METHOD: Data
      were collected from 25 emergency nurses during three focus group interviews. The
      interviews were transcribed and analysed using the qualitative techniques of
      grounded theory. RESULTS: Ten categories emerged from the data that described a
      social process for managing death in the emergency department. The categories
      were linked via the core category labelled 'dying in the emergency department is
      not ideal', which described how the emergency department was an inappropriate
      place for death to occur. To help manage the influence of the environment on end
      of-life care, nurses reported strategies that included moving dying patients out
      of the emergency department and providing the best care that they could.
      CONCLUSION: The results of this study highlight nurses' belief that the emergency
      department was not an appropriate place for death to occur. Despite being
      frequently exposed to death and dying, the actions and attitudes of emergency
      nurses implied the need or desire to avoid death in the emergency department.

PMID- 25851918
TI  - Human performance on random ratio and random interval schedules, performance
      awareness and verbal instructions.
AB  - Humans responded on multiple random-ratio (RR) random-interval (RI) schedules,
      and their verbalized performance awareness (PA; i.e., their ability to accurately
      describe what they did) was measured in three experiments. In Experiment 1,
      instructions informed participants that to earn points, either sometimes rapid
      responding and sometimes slow responding would work best (accurate instructions);
      rapid responding would work best (go fast instructions); spaced responding would
      work best (go slow instructions); or no advice was provided (minimal
      instructions). In Experiments 2 and 3, participants received either accurate or
      minimal instructions and were subject to extinction after a multiple RR-RI
      schedule. In all experiments, both performance awareness, and receiving accurate
      instructions, were related to schedule-sensitive responding, but were unrelated
      to one another - participants receiving accurate-rate instructions were not more
      likely to show performance awareness than those exposed to minimal instructions.
      Both higher performance awareness and exposure to accurate instructions predicted
      faster extinction in Experiment 2 but not in Experiment 3. The current results
      suggest that performance awareness rather than contingency awareness is more
      strongly related to humans displaying schedule-typical behavior and that this is
      not strongly related to any explicit verbal instructions that are given. 

PMID- 25851919
TI  - Strain-dependent variations in visceral sensitivity: relationship to stress,
      anxiety and spinal glutamate transporter expression.
AB  - Responses to painful stimuli differ between populations, ethnic groups, sexes and
      even among individuals of a family. However, data regarding visceral pain are
      still lacking. Thus, we investigated differences in visceral nociception across
      inbred and outbred mouse strains using colorectal distension. Anxiety and
      depression-like behaviour were assessed using the open field and forced swim test
      as well as the corticosterone stress response. Possible mechanistic targets
      [excitatory amino acid transporter (EAAT-1), brain-derived neurotrophic factor
      (BDNF) and 5HT1A receptor] were also assessed using quantitative real-time
      polymerase chain reaction. Adult, male, inbred and outbred mouse strains were
      used in all assays (inbred strains; CBA/J Hsd, C3H/HeNHsd, BALB/c OlaHsd, C57
      BL/6JOlaHsd, DBA/2J RccHsd, CAST/EiJ, SM/J, A/J OlaHsd, 129P2/OlaHsd, FVB/NHan
      Hsd and outbred strains: Swiss Webster, CD-1). mRNA expression levels of EAAT-1,
      BDNF and 5HT1A receptor (HTR1A) were quantified in the lumbosacral spinal cord,
      amygdala and hippocampus. A significant effect of strain was found in visceral
      sensitivity, anxiety and depressive-like behaviours. Strain differences were also
      seen in both baseline and stress-induced corticosterone levels. CBA/J mice
      consistently exhibited heightened visceral sensitivity, anxiety behaviour and
      depression-like behaviour which were associated with decreased spinal EAAT-1 and
      hippocampal BDNF and HTR1A. Our results show the CBA/J mouse strain as a novel
      mouse model to unravel the complex mechanisms of brain-gut axis disorders such as
      irritable bowel syndrome, in particular the underlying mechanisms of visceral
      hypersensitivity, for which there is great need. Furthermore, this study
      highlights the importance of genotype and the consequences for future development
      of transgenic strains in pain research. 

PMID- 25851920
TI  - Detection of Dirofilaria immitis and other arthropod-borne filarioids by an HRM
      real-time qPCR, blood-concentrating techniques and a serological assay in dogs
      from Costa Rica.
AB  - BACKGROUND: Canine filarioids are important nematodes transmitted to dogs by
      arthropods. Diagnosis of canine filariosis is accomplished by the microscopic
      identification of microfilariae, serology or PCR for filarial-DNA. The aim of
      this study was to evaluate a molecular assay for the detection of canine filariae
      in dog blood, to compare its performance to other diagnostic techniques, and to
      determine the relationship between microfilarial concentration and infection with
      other vector-borne pathogens. METHODS: Blood samples from 146 dogs from Costa
      Rica were subjected to the detection of canine filarioids by four different
      methods: the microhematocrit tube test (MCT), Knott's modified test, serology and
      a high resolution melt and quantitative real-time PCR (HRM-qPCR). Co-infection
      with other vector-borne pathogens was also evaluated. RESULTS: Fifteen percent of
      the dogs were positive to Dirofilaria immitis by at least one of the methods. The
      HRM-qPCR produced distinctive melting plots for the different filarial worms and
      revealed that 11.6% of dogs were infected with Acanthocheilonema reconditum. The
      latter assay had a limit of detection of 2.4x10-4 mf/MUl and detected infections
      with lower microfilarial concentrations in comparison to the microscopic
      techniques and the serological assay. The MCT and Knott's test only detected dogs
      with D. immitis microfilaremias above 0.7 mf/MUl. Nevertheless, there was a
      strong correlation between the microfilarial concentration obtained by the
      Knott's modified test and the HRM-qPCR (r = 0.906, p < 0.0001). Interestingly,
      one dog was found infected with Cercopithifilaria bainae infection. Moreover, no
      association was found between microfilaremia and co-infection and there was no
      significant difference in microfilarial concentration between dogs infected only
      with D. immitis and dogs co-infected with Ehrlichia canis, Anaplasma platys or
      Babesia vogeli. CONCLUSIONS: This is the first report of A. reconditum and C.
      bainae in Costa Rica and Central America. Among the evaluated diagnostic
      techniques, the HRM-qPCR showed the most sensitive and reliable performance in
      the detection of blood filaroids in comparison to the Knott's modified test, the
      MCT test and a serological assay.

PMID- 25851921
TI  - Molecular cytogenetic characterization of a 2q35-q37 duplication and a 4q35.1
      q35.2 deletion in two cousins: a genotype-phenotype analysis.
AB  - The 2q3 duplication and 4q3 deletion are two distinct conditions with variable
      phenotypes including developmental delay, intellectual disability, Pierre Robin
      sequence (PRS), and cardiovascular, craniofacial, digital and skeletal anomalies.
      We describe two cousins, a 37-year-old man (Patient 1) and a 17-year-old girl
      (Patient 2), with a derivative chromosome leading to a 4q35 deletion-2q35q37
      duplication. Conventional karyotype showed in both patients the same
      rearrangement derived from unbalanced segregation of a parental reciprocal
      translocation involving the long arms of chromosome 2 and 4. Patient 1's father
      and Patient 2's mother were identified as the carriers of a balanced
      translocation t(2;4)(q35;q35). Array-CGH analysis, performed to characterize the
      rearrangement, documented in both patients the presence of a 26 Mb duplication of
      the 2q35-q37.3 region of chromosome 2 and a 6.3 Mb deletion of the 4q35.1-q35.2
      region of chromosome 4. Both patients showed intellectual disability, minor
      facial, and digital anomalies, hearing, ocular, and genitourinary abnormalities.
      The comparison of their features with those of published cases of 2q3 duplication
      and 4q3 deletion allowed us to further delineate the genotype-phenotype
      correlation as well as the combined effect of partial 2q duplication and 4q
      deletion syndromes in adulthood.

PMID- 25851922
TI  - Ultrasensitive Molecular Beacon Designed with Totally Serinol Nucleic Acid (SNA)
      for Monitoring mRNA in Cells.
AB  - An artificial nucleic acid based on acyclic serinol building blocks and termed
      "serinol nucleic acid" (SNA) was used to construct a fluorescent probe for RNA
      visualization in cells. The molecular beacon (MB) composed of only SNA with a
      fluorophore at one terminus and a quencher at the other was resistant to
      enzymatic digestion, due to its unnatural acyclic scaffold. The SNA-MB could
      detect its complementary RNA with extremely high sensitivity; the signal-to
      background (S/B) ratio was as high as 930 when perylene and anthraquinone were
      used as the fluorophore and quencher pair. A high S/B ratio was also achieved
      with SNA-MB tethering the conventional Cy3 fluorophore, and this probe enabled
      selective visualization of target mRNA in fixed cells. Thus, SNA-MB has potential
      for use as a biological tool capable of visualizing RNA in living cells. 

PMID- 25851923
TI  - High-grade fetal adenocarcinoma of the lung is a tumour with a fetal phenotype
      that shows diverse differentiation, including high-grade neuroendocrine
      carcinoma: a clinicopathological, immunohistochemical and mutational study of 20
      cases.
AB  - AIMS: High-grade fetal adenocarcinoma (H-FLAC) is a rare variant of pulmonary
      adenocarcinoma; this study aims to elucidate its clinicopathological features and
      genetic abnormalities. METHODS AND RESULTS: Clinicopathological,
      immunohistochemical and mutational analyses were performed on 20 surgically
      resected lung cancers that showed H-FLAC histology in various proportions. These
      tumours predominantly occurred in elderly males and in 10 patients who were heavy
      smokers. Four cases were pure H-FLAC, and 16 cases were mixed H-FLAC, which were
      found to be combined with conventional-type adenocarcinoma (15 cases), large-cell
      neuroendocrine carcinoma (three cases), small-cell carcinoma (one case), enteric
      adenocarcinoma (two cases), choriocarcinoma (two cases), and a solid-clear cell
      pattern (seven cases). The fetal phenotype and diverse differentiation were
      supported by the immunoexpression of alpha-fetoprotein (95%), thyroid
      transcription factor-1 (TTF-1) (50%), neuroendocrine markers (30-45%), proneural
      markers (50-69%), and CDX2 (40%). Except for TTF-1 expression (pure H-FLACs, 0%;
      mixed H-FLACs, 63%), there were no significant differences in histological or
      immunohistochemical findings between pure and mixed H-FLACs. EGFR, KRAS, BRAF and
      PIK3CA mutations were identified in 20%, 0%, 0% and 7% of the tumours,
      respectively. CONCLUSIONS: Lung adenocarcinomas with H-FLAC features possess the
      potential for multidirectional differentiation, and are not strongly associated
      with known major driver gene mutations.

PMID- 25851924
TI  - Sanfilippo syndrome: Overall review.
AB  - Mucopolysaccharidosis type III (MPS III, Sanfilippo syndrome) is a lysosomal
      storage disorder, caused by a deficiency in one of the four enzymes involved in
      the catabolism of glycosaminoglycan heparan sulfate. It is characterized by
      progressive cognitive decline and severe hyperactivity, with relatively mild
      somatic features. This review focuses on clinical features, diagnosis, treatment,
      and follow-up of MPS III, and provides information about supplementary tests and
      differential diagnosis. Given that few reviews of MPS III have been published,
      several studies were compiled to establish diagnostic recommendations.
      Quantitative urinary glycosaminoglycan analysis is strongly recommended, and
      measurement of disaccharides, heparin cofactor II-thrombin complex and
      gangliosides is also used. Enzyme activity of the different enzymes in blood
      serum, leukocytes or fibroblasts, and mutational analysis for SGSH, NAGLU, HGSNAT
      or GNS genes are required to confirm diagnosis and differentiate four subtypes of
      MPS III. Although there is no global consensus for treatment, enzyme replacement
      therapy and gene therapy can provide appropriate results. In this regard, recent
      publications on treatment and follow-up are discussed. 

PMID- 25851925
TI  - Acute aortic syndromes: current status.
AB  - The term acute aortic syndrome comprises aortic dissection, intramural hematoma,
      and penetrating atherosclerotic ulcer. The most recent developments in acute
      aortic syndromes include (1) a change in the mindset that each entity is
      pathologically distinct, with a shift toward considering the acute aortic
      syndromes as points along a spectrum of aortic disease, (2) the optimization of
      aortic imaging quality and radiation dose, and (3) surgical or endovascular
      management. This review article focuses on how these developments pertain to
      thoracic radiologists. 

PMID- 25851926
TI  - Diet inclusion of devil fish (Plecostomus spp.) silage and its impacts on ruminal
      fermentation and growth performance of growing lambs in hot regions of Mexico.
AB  - The aim of this study was to evaluate the inclusion of devil fish (Plecostomus
      spp.-DF) silage in Criollo * Blackbelly lamb diets in hot region of Guerrero
      state of Mexico. Rumen fermentation including pH, volatile fatty acids (VFA) and
      ammonia-N (NH3-N) and productive variables including feed intake (FI), average
      daily gain (ADG), and feed conversion were determined. Twenty lambs with 18 +/-
      1.2 kg body weight in a completely randomized design were fed a total mixed
      ration (TMR) of concentrate (based on soybean meal, whole oat hay, ground corn
      cob, vitamins-minerals supplement) with DF silage at 0 % (DF0), 9 % (DF9), 18 %
      (DF18), and 27 % (DF27) of the TMR for 75 days. The ruminal pH showed no
      difference (P > 0.05) between treatments: ranging between 6.21 and 6.36.
      Propionic acid molar proportions showed an irregular pattern between experimental
      groups, which only differed (P < 0.05) between DF9 and DF27, without differences
      between the other treatments. A greater molar proportion of butyric acid was
      noted (P < 0.05) in DF27 when compared to the other treatments. The ruminal
      concentration of NH3-N showed some insignificant differences (P > 0.05) among
      treatments. The daily FI was increased (P < 0.01) in DF27 (1.131 g) when compared
      with DF0, while DF9 and DF18 showed intermediate consumption with no differences
      (P > 0.05) among them. The ADG showed only difference (cubic effect, P = 0.02)
      between DF9 and DF18. The highest feed conversion was observed (cubic effect, P <
      0.01) with DF18, with a value of 4.7 kg of feed to gain 1 kg of body weight. It
      could be concluded that the inclusion of up to 18 % of DF silage in the TMR of
      growing lamb diets, in hot regions of Mexico, may improve productive performance
      and ruminal fermentation kinetics, without any negative effects. 

PMID- 25851927
TI  - Effects of processing corn on the carcass traits and meat quality of feedlot
      lambs.
AB  - The objectives of this study were to evaluate and compare the effect of the corn
      grain processing (whole grain, dry beans ground, and wet grain) on carcass
      characteristics and meat quality in lambs. Twenty-two Dorper vs. Santa Ines
      uncastrated lambs (27 +/- 4 kg BW; +/-3 months old) were distributed in a
      randomized complete block (initial BW). The diets were composed of 20 % protein
      mineral pellet, 5 % hay, and 75 % corn in the form of whole grain, ground grain,
      or wet grain. The harvest weight of animals fed whole corn (50.2 kg) and ground
      (49.03 kg) were equal and higher than the moisture corn fed lambs (44.89 kg);
      therefore, the same differences were expected to be seen in the cold vs hot
      carcass comparison. However, there was no difference between treatments comparing
      hot or cold carcass performance, averaging 47 and 46 %, respectively. Also
      unaffected by the treatments were subcutaneous fat thickness values, loin muscle
      area, pH, temperature, drip loss, water loss by cooking, color, and tenderness.
      It can be concluded that the shape and size of corn grain in diets of high
      concentrate resulted in no measurable influence on carcass traits, but whole
      grain is more easily managed by the producer. 

PMID- 25851928
TI  - Relationships between heat stress and metabolic and milk parameters in dairy cows
      in Southern Brazil.
AB  - This study approached the relationships between heat stress and metabolic and
      milk parameters in a commercial herd of Holstein cows located in southern Brazil.
      A total of 50 multiparous cows at different lactations and lactation stages were
      selected in order to obtain 450 samples during two consecutive years (2011 and
      2012). The animals were fed a partial mixed ration along with ryegrass pasture in
      a semi-confinement system. Blood, milk, and urine samples were taken during the
      summer and winter for a total of eight samples. Three intervals of temperature
      humidity index (THI) were established during the summer months (January and
      February) as follows: low group (LOW), THI between 75 and 81 (N = 100); moderate
      group (MOD), THI between 81 and 82 (N = 150); and severe group (SEV), THI between
      83 and 90 (N = 150). The group of cows sampled during winter (July) constituted
      the control group (CON; THI = 59, N = 50). Increased total protein, albumin,
      glucose, and cholesterol occurred in heat-stressed cows. Increased AST activity
      was also observed in heat-stressed cows, but triglycerides and beta-OH-butyrate
      did not show any difference among groups. Lower lactate and higher pO2 were seen
      in cows with heat stress than CON. Cows in SEV had a 21 % milk yield decrease,
      while lactose and protein decreased with fat not being affected. Heat stress had
      strong effects on metabolic, clinical, and performance parameters in Holstein
      cows. 

PMID- 25851929
TI  - "Ormilo disease" a disorder of zebu cattle in Tanzania: bovine cerebral
      theileriosis or new protozoan disease?
AB  - "Ormilo" disease is a neurological disorder of cattle described by Maasai herders
      in Tanzania. It is attributed to infection by Theileria species, although no
      detailed data are available in the literature. The authors describe the
      macroscopical and histological changes observed in 30 brains of indigenous short
      horn zebu cattle from Northern Tanzania, aged 2-9 years, with the characteristic
      neurological signs of "Ormilo". Moreover, the ultrastructural details observed in
      14 selected brain samples were reported. Areas of congestion and hemorrhages,
      associated with the obstruction of the cerebral vessels with large numbers of
      parasitized lymphoid cells, were observed. Electron microscopy showed the
      presence of intralymphocytic parasites morphologically comparable to flagellated
      protozoa, not previously described in the lymphoid cells of cattle, but only
      reported during the sexual stages within the vector. Theileria taurotragi was
      detected by polymerase chain reaction (PCR) and reverse line blot (RLB) in nine
      samples. The authors hypothesize that the parasite detected by electron
      microscopy could be a strain of a Theileria endemic to this region till now not
      investigated, having an intralymphocytic phase and being associated with other
      Theileria spp. infestation. Further studies are needed to better understand the
      etiology of "Ormilo" disease and to characterize the morphology of the observed
      parasite, clarifying its role in the disease in Tanzania. 

PMID- 25851930
TI  - Improving rumen ecology and microbial population by dried rumen digesta in beef
      cattle.
AB  - Four Thai native beef cattle with initial body weight (BW) of 91.8 +/- 4.75 kg
      were randomly assigned according to a 4 * 4 Latin square design to receive four
      concentrates replacement levels of soybean meal (SBM) by dried rumen digesta
      (DRD) at 0, 33, 67, and 100 % on dry matter (DM) basis. All cattle were fed rice
      straw ad libitum while additional concentrate was fed at 0.5 % BW daily. The
      experiment was conducted for four periods of 21 days. Rumen fluid was analyzed
      for predominant cellulolytic bacterial population by using real-time PCR
      technique. Increasing levels of DRD did not alter total feed intake, ruminal pH
      and temperature, and plasma urea nitrogen (P > 0.05). Protozoa and fungal
      population were not differed by DRD supplementation while population of bacteria
      at 4 h post feeding was increased when SBM was replaced with DRD at 66 and 100 %
      DM. Population of total bacteria and R. flavefaciens at 4 h post feeding were
      significantly highest with inclusion of 100 % of DRD in the ration. The
      experimental diets has no effect on excretion and absorption of purine
      derivatives (P > 0.05), while microbial crude protein and efficiency of microbial
      N synthesis were significantly increased with DRD inclusion in the diet and
      highest with 100 % DRD replacement (P > 0.05). Replacement of SBM by DRD at 100 %
      DM improved the rumen ecology and microbial population in beef cattle fed on rice
      straw. 

PMID- 25851931
TI  - Factors affecting response to proton pump inhibitor therapy in patients with
      gastroesophageal reflux disease: a multicenter prospective observational study.
AB  - BACKGROUND: Proton pump inhibitor (PPI) therapy, the first-line treatment for
      gastroesophageal reflux disease (GERD), is not always effective. This study aimed
      to examine the effect of pretreatment patient characteristics on response to PPI
      therapy. METHODS: Japanese outpatients with symptomatic GERD scheduled to receive
      endoscopy and PPI therapy were enrolled in this multicenter prospective
      observational study. The patients' characteristics, including GERD and dyspeptic
      symptoms, anxiety, depression, and quality of life, were assessed using
      questionnaires before and 2 and 4 weeks after the start of PPI therapy. Factors
      affecting therapeutic response were examined by simple and multiple regression
      analyses using three patient-reported outcome measures as objective variables.
      RESULTS: Data from 182 patients were analyzed. In multiple regression analysis
      using the residual symptom rate as an objective variable, lower GERD symptom
      score (p < 0.05), absence of erosive esophagitis (p < 0.05), higher epigastric
      pain/burning symptom score (p < 0.05), and higher depression subscale score (p <
      0.05) accompanied poorer therapeutic response. In analyses using the patient's
      impression of therapy, lower GERD symptom score (p < 0.05) and absence of erosive
      esophagitis (p < 0.05) accompanied poorer therapeutic response. In analyses using
      the relative GERD symptom intensity evaluated using a numeric rating scale, lower
      GERD symptom score (p < 0.05), higher epigastric pain/burning symptom score (p <
      0.1), and lower body mass index (p < 0.05) accompanied poorer therapeutic
      response. CONCLUSIONS: Patients who complained of milder GERD symptoms before
      treatment were likely to have poorer response to PPI therapy. Association of
      absence of erosive esophagitis, severer epigastric pain/burning symptoms, lower
      body mass index, and severer depression with poorer therapeutic response was also
      suggested.

PMID- 25851933
TI  - Estimating time-varying RSA to examine psychophysiological linkage of marital
      dyads.
AB  - One of the primary tenets of polyvagal theory dictates that parasympathetic
      influence on heart rate, often estimated by respiratory sinus arrhythmia (RSA),
      shifts rapidly in response to changing environmental demands. The current
      standard analytic approach of aggregating RSA estimates across time to arrive at
      one value fails to capture this dynamic property within individuals. By utilizing
      recent methodological developments that enable precise RSA estimates at smaller
      time intervals, we demonstrate the utility of computing time-varying RSA for
      assessing psychophysiological linkage (or synchrony) in husband-wife dyads using
      time-locked data collected in a naturalistic setting. 

PMID- 25851932
TI  - Ultrasound molecular imaging: Moving toward clinical translation.
AB  - Ultrasound is a widely available, cost-effective, real-time, non-invasive and
      safe imaging modality widely used in the clinic for anatomical and functional
      imaging. With the introduction of novel molecularly-targeted ultrasound contrast
      agents, another dimension of ultrasound has become a reality: diagnosing and
      monitoring pathological processes at the molecular level. Most commonly used
      ultrasound molecular imaging contrast agents are micron sized, gas-containing
      microbubbles functionalized to recognize and attach to molecules expressed on
      inflamed or angiogenic vascular endothelial cells. There are several potential
      clinical applications currently being explored including earlier detection,
      molecular profiling, and monitoring of cancer, as well as visualization of
      ischemic memory in transient myocardial ischemia, monitoring of disease activity
      in inflammatory bowel disease, and assessment of arteriosclerosis. Recently, a
      first clinical grade ultrasound contrast agent (BR55), targeted at a molecule
      expressed in neoangiogenesis (vascular endothelial growth factor receptor type 2;
      VEGFR2) has been introduced and safety and feasibility of VEGFR2-targeted
      ultrasound imaging is being explored in first inhuman clinical trials in various
      cancer types. This review describes the design of ultrasound molecular imaging
      contrast agents, imaging techniques, and potential future clinical applications
      of ultrasound molecular imaging.

PMID- 25851934
TI  - Hematopoietic progenitor cells collection in pediatric patients with brain tumor.
AB  - AIM: To analyze the efficacy and safety of hematopoietic progenitor cells (HPC)
      collections by leukapheresis in pediatric patients with brain tumors. RESULTS:
      Between 2003 and 2014, we collected HPC from 19 children (12 boys/7 girls),
      median age at the diagnosis of 5 years old (<1-15 years old) and weight of 16.8
      Kg (6.7-42). Diagnoses were Medulloblastoma (n = 10), Primitive Neuroectodermal
      Tumor (n = 5), Atypical Teratoid Rhabdoid Tumor (n = 3) and Secreting Germ Cell
      Tumor (n = 1). All patients performed leukapheresis by a central venous catheter,
      at the fifth day of mobilization with G-CSF (median dose 11.7 ug/Kg/day), 9 of
      them with COBE(r) Spectra and 10 with Spectra Optia(r). The anticoagulant used
      was ACD-A, ratio of 14:1 or ACD-A plus heparin, ratio 25:1. The tubing set was
      primed with a compatible, irradiated, leukodepleted and hematocrit adjusted
      packed red cells for all children <30 kg (n = 17). A median of 1.5 (1-3)
      leukapheresis per patient was performed with an average of 3 (1.5-5.4) blood
      volumes processed; 3 children did a second mobilization and one additional
      leukapheresis. The median number of CD34+ cells collected was 4.6 * 10(6) /Kg
      (0.18-22.6) of patient body weight; 12 children collected for a tandem
      transplant. The median time between cell collection and infusion was 3 (0.6-9.1)
      months. CONCLUSIONS: HPC collection in children is an efficient and well
      tolerated technique, performed as an outpatient procedure. With the new
      mobilization schemes and leukapheresis technology, we can collect a high number
      of HPC allowing pediatric oncologist to establish more aggressive chemotherapy
      protocols hoping to improve patient outcome.

PMID- 25851936
TI  - Osteocytes and Homeostasis of Remote Organs : Bone-Buried Osteocytes Talk to
      Remote Organs.
AB  - The study of bones has attracted researchers from many medical fields. To
      understand bone-organ interactions, hematologists were challenged to investigate
      bone marrow (BM), the core of bone where hematopoiesis takes place. Through
      studies of the hematopoietic stem cells niche, hematologists contributed to the
      discovery of unexpected functions of bone-forming osteoblasts and bone-buried
      osteocytes. In particular, the recent findings about osteocytes, as the
      regulatory system of lympho-hematopoiesis and fat metabolism, highlighted the
      central role of skeletal tissue in inter-organ communication. The cross-cutting
      consideration including hematology and many other fields will expand the bone
      research. 

PMID- 25851935
TI  - GNAS Spectrum of Disorders.
AB  - The GNAS complex locus encodes the alpha-subunit of the stimulatory G protein
      (Gsalpha), a ubiquitous signaling protein mediating the actions of many hormones,
      neurotransmitters, and paracrine/autocrine factors via generation of the second
      messenger cAMP. GNAS gives rise to other gene products, most of which exhibit
      exclusively monoallelic expression. In contrast, Gsalpha is expressed
      biallelically in most tissues; however, paternal Gsalpha expression is silenced
      in a small number of tissues through as-yet-poorly understood mechanisms that
      involve differential methylation within GNAS. Gsalpha-coding GNAS mutations that
      lead to diminished Gsalpha expression and/or function result in Albright's
      hereditary osteodystrophy (AHO) with or without hormone resistance, i.e.,
      pseudohypoparathyroidism type-Ia/Ic and pseudo-pseudohypoparathyroidism,
      respectively. Microdeletions that alter GNAS methylation and, thereby, diminish
      Gsalpha expression in tissues in which the paternal Gsalpha allele is normally
      silenced also cause hormone resistance, which occurs typically in the absence of
      AHO, a disorder termed pseudohypoparathyroidism type-Ib. Mutations of GNAS that
      cause constitutive Gsalpha signaling are found in patients with McCune-Albright
      syndrome, fibrous dysplasia of bone, and different endocrine and non-endocrine
      tumors. Clinical features of these diseases depend significantly on the parental
      allelic origin of the GNAS mutation, reflecting the tissue-specific paternal
      Gsalpha silencing. In this article, we review the pathogenesis and the phenotypes
      of these human diseases.

PMID- 25851937
TI  - Disease characteristics, treatment patterns, prognosis, outcomes and lymphoma
      related mortality in elderly follicular lymphoma in the United States.
AB  - Data from the National LymphoCare Study (a prospective, multicentre registry that
      enrolled follicular lymphoma (FL) patients from 2004 to 2007) were used to
      determine disease characteristics, treatment patterns, outcomes and prognosis for
      elderly FL (eFL) patients. Of 2650 FL patients, 209 (8%) were aged >80 years;
      these eFL patients more commonly had grade 3 disease, less frequently received
      chemoimmunotherapy and anthracyclines, and had lower response rates when compared
      to younger patients. With a median follow-up of 6.9 years, 5-year overall
      survival (OS) for eFL patients was 59%; 38% of deaths were lymphoma-related. No
      treatment produced superior OS among eFL patients. In multivariate Cox models,
      anaemia, B-symptoms and male sex predicted worse OS (P < 0.01); a prognostic
      index of these factors (0, 1 or >= 2 present) predicted OS [hazard ratio (95%
      CI): >= 2 vs. 0, 4.72 (2.38-9.33); 1 vs. 0, 2.63 (1.39-4.98)], with a higher
      concordance index (0.63) versus the Follicular Lymphoma International Prognostic
      Index (0.55). The index was validated in an independent cohort. In the largest
      prospective US-based eFL cohort, no optimal therapy was identified and nearly 40%
      of deaths were lymphoma-related, representing baseline outcomes in the modern
      era.

PMID- 25851939
TI  - Structural insight of glitazone for hepato-toxicity: Resolving mystery by PASS.
AB  - Troglitazone causes severe hepatic injury in certain individuals and multiple
      mechanisms related to hepato-toxicity has been reported creating confusion. In
      the present study, the mechanism for the hepatic injury of glitazones was
      investigated by PASS. The results suggest that chromane containing glitazones are
      apoptic agonist (activating p53 by intrinsic pathway leading to the apoptosis)
      and those which do not contain the chromane are devoid of this. In case of hepato
      toxicity by non-chromane glitazone and their metabolite such as M-3, RM-3,
      rosiglitazone and pioglitazone; PASS suggest that these chemicals are not apoptic
      agonist but they are the substrate for CYP enzyme (Phase-I Oxidative Enzyme) and
      Phase-II conjugating enzymes; interfering with bile acid metabolism rendering
      bile acid more toxic (cholestasis). This unmetabolised bile salt further
      initiates the process apoptosis via intrinsic and extrinsic pathway leading to
      the apoptosis. Immunoblot analysis further confirm our hypothesis that
      troglitazone (chromane containing glitazone), but not rosiglitazone and
      pioglitazone (non-chromane containing glitazone) increased the levels of p53 in a
      time-dependent manner. Hence our prediction related to the mechanism of hepato
      toxicity by apoptosis and structural insight of glitazone can be helpful in
      improving the drug profile of this category. 

PMID- 25851938
TI  - Tricyclic 1,5-naphthyridinone oxabicyclooctane-linked novel bacterial
      topoisomerase inhibitors as broad-spectrum antibacterial agents-SAR of left-hand
      side moiety (Part-2).
AB  - Novel bacterial topoisomerase inhibitors (NBTIs) represent a new class of broad
      spectrum antibacterial agents targeting bacterial Gyrase A and ParC and have
      potential utility in combating antibiotic resistance. A series of novel
      oxabicyclooctane-linked NBTIs with new tricyclic-1,5-naphthyridinone left hand
      side moieties have been described. Compounds with a (R)-hydroxy-1,5
      naphthyridinone moiety (7) showed potent antibacterial activity (e.g.,
      Staphylococcus aureus MIC 0.25 MUg/mL), acceptable Gram-positive and Gram
      negative spectrum with rapidly bactericidal activity. The compound 7 showed
      intravenous and oral efficacy (ED50) at 3.2 and 27 mg/kg doses, respectively, in
      a murine model of bacteremia. Most importantly they showed significant
      attenuation of functional hERG activity (IC50 >170 MUM). In general, lower logD
      attenuated hERG activity but also reduced Gram-negative activity. The co-crystal
      structure of a hydroxy-tricyclic NBTI bound to a DNA-gyrase complex exhibited a
      binding mode that show enantiomeric preference for R isomer and explains the
      activity and SAR. The discovery, synthesis, SAR and X-ray crystal structure of
      the left-hand-side tricyclic 1,5-naphthyridinone based oxabicyclooctane linked
      NBTIs are described.

PMID- 25851940
TI  - Development of methyl isoxazoleazepines as inhibitors of BET.
AB  - In this report we detail the evolution of our previously reported thiophene
      isoxazole BET inhibitor chemotype exemplified by CPI-3 to a novel bromodomain
      selective chemotype (the methyl isoxazoleazepine chemotype) exemplified by
      carboxamide 23. The methyl isoxazoleazepine chemotype provides potent inhibition
      of the bromodomains of the BET family, excellent in vivo PK across species, low
      unbound clearance, and target engagement in a MYC PK-PD model. 

PMID- 25851941
TI  - Making water-soluble integral membrane proteins in vivo using an amphipathic
      protein fusion strategy.
AB  - Integral membrane proteins (IMPs) play crucial roles in all cells and represent
      attractive pharmacological targets. However, functional and structural studies of
      IMPs are hindered by their hydrophobic nature and the fact that they are
      generally unstable following extraction from their native membrane environment
      using detergents. Here we devise a general strategy for in vivo solubilization of
      IMPs in structurally relevant conformations without the need for detergents or
      mutations to the IMP itself, as an alternative to extraction and in vitro
      solubilization. This technique, called SIMPLEx (solubilization of IMPs with high
      levels of expression), allows the direct expression of soluble products in living
      cells by simply fusing an IMP target with truncated apolipoprotein A-I, which
      serves as an amphipathic proteic 'shield' that sequesters the IMP from water and
      promotes its solubilization. 

PMID- 25851943
TI  - Linearly tunable emission colors obtained from a fluorescent-phosphorescent dual
      emission compound by mechanical stimuli.
AB  - Organic mechanoluminochromic materials are mechano/piezo-responsive and promising
      for applications in sensors, displays, and data storage devices. However, their
      switching range of emission is seriously impeded by only one kind of emission
      (either a fluorescent or phosphorescent peak) in the spectrum of single organic
      compounds. This study presents a design strategy for pure organic compounds with
      excellent room-temperature fluorescent-phosphorescent dual-emission (rFPDE)
      properties, which combines the effective factors of dipenylsulfone group,
      crystalline state, and heavy atom effect. Following the principle of color
      mixing, myriad emission colors with a wide range from orange to purple and across
      white zone in a straight line in the chromaticity diagram of the Commission
      Internationale de l'Eclairage (CIE) can be obtained by simply mechanical grinding
      the compound. The unique properties could be concentrated on a pure organic
      compound through this design strategy, which provides a new efficient channel for
      the discovery of efficient mechano-responsive organic materials. 

PMID- 25851942
TI  - A phase II study of perioperative S-1 combined with weekly docetaxel in patients
      with locally advanced gastric carcinoma: clinical outcomes and
      clinicopathological and pharmacogenetic predictors for survival.
AB  - BACKGROUND: We conducted a phase II study to evaluate the efficacy and safety of
      perioperative S-1 plus docetaxel in locally advanced gastric cancer (LAGC) and to
      investigate the association between CYP2A6 genotype and outcome. METHODS:
      Patients with LAGC [clinical stage III-IV (M0) by the Japanese staging system]
      received three cycles of pre- and postoperative chemotherapy (S-1 40 mg/m(2)
      twice daily on days 1-14; intravenous docetaxel 35 mg/m(2) on days 1 and 8, every
      3 weeks) followed by gastrectomy with D2 dissection. We also performed a
      pharmacokinetic and CYP2A6 genotyping study (*1, *4, *7, *9, *10) for S-1.
      RESULTS: From October 2006 to June 2008, 44 patients entered the study. 43
      eligible patients completed preoperative chemotherapy and 40 completed
      postoperative chemotherapy. The most common G3/4 toxicities during pre- and
      postoperative chemotherapy were neutropenia, stomatitis, and abdominal pain. The
      clinical response rate by RECIST was 74.4 % (95 % CI, 61.4-87.4 %), and the R0
      resection rate was 97.7 %. Clinical downstaging in T or N occurred in 41.9 % of
      patients. The 3-year progression-free survival (PFS) rate was 62.8 % and 5-year
      overall survival (OS) rate was 69.6 %. PFS and OS differed significantly
      according to clinical response, clinical downstaging, and CYP2A6 genotype.
      Patients with CYP2A6 variant/variant genotypes had a higher tegafur C max and
      worse survival than those with wild/wild or wild/variant genotypes. CONCLUSION:
      Perioperative S-1 plus docetaxel is active with a manageable toxicity in patients
      with LAGC receiving D2 surgery. Clinical tumor response, clinical downstaging,
      and CYP2A6 genotype may predict efficacy.

PMID- 25851944
TI  - Cell type-specific in vivo expression of genes encoding signalling molecules in
      the brain in response to chronic mild stress and chronic treatment with
      fluoxetine.
AB  - RATIONALE: Previously, we reported that chronic treatment with fluoxetine
      increased gene expression of 5-hydroxytryptamine receptor 2B (5-HT2BR), cytosolic
      phospholipase 2alpha (cPLA2alpha), glutamate receptor, ionotropic kainate 2
      (GluK2) and adenosine deaminase acting on RNA 2 (ADAR2), in cultured astrocytes
      and astrocytes freshly isolated from transgenic mice tagged with an astrocyte
      specific marker. In contrast, neurones isolated from transgenic mice tagged with
      a neurone-specific marker and exposed to fluoxetine showed an increase in gene
      expression of glutamate receptor, ionotropic kainate 4 (GluK4) and 5
      hydroxytryptamine receptor 2C (5-HT2CR). In a mouse model of anhedonia, the
      downregulation of 5-HT2BR, cPLA2alpha, ADAR2 and GluK4 but not GluK2 and 5-HT2CR
      was detected. OBJECTIVE: To investigate the effects of chronic mild stress (CMS)
      and/or fluoxetine treatment on gene expression of 5-HT2BR, 5-HT2CR, cPLA2alpha,
      ADAR2, GluK2 and GluK4 specifically in astrocytes and neurones. METHODS:
      Transgenic mice tagged with either astrocyte- or neurone-specific markers were
      exposed to the CMS. Real-time PCR was applied to determine expression of
      messenger RNA (mRNA). RESULTS: We found that (i) mRNAs of the 5-HT2BR and
      cPLA2alpha in astrocytes and GluK4 in neurones were significantly reduced in mice
      that became anhedonic; the mRNA levels were restored by fluoxetine treatment;
      (ii) ADAR2 in astrocytes was decreased by the CMS but showed no response to
      fluoxetine in anhedonic animals; (iii) neither GluK2 expression in astrocytes nor
      5-HT2CR expression in neurones were affected in anhedonic animals, although
      expression of 5-HT2CR mRNA was upregulated by fluoxetine. CONCLUSIONS: Our
      results indicate that the effects of chronic treatment with fluoxetine are not
      only dependent on the cell type studied but also on the development of anhedonia.
      This suggests that fluoxetine may affect major depression (MD) patients and
      healthy people in a different manner.

PMID- 25851946
TI  - Cecal diverticulitis is a challenging diagnosis: a report of 3 cases.
AB  - BACKGROUND: Cecal diverticulitis is an uncommon cause of acute abdominal pain and
      presents clinically similar to acute appendicitis. There are many perspectives
      concerning the management of this condition, ranging from different types of
      surgical resections to conservative treatment with antibiotics. CASE REPORT: We
      present 3 cases of cecal diverticulitis. One of the patients was treated
      conservatively with intravenous antibiotics and the other 2 were treated with
      surgical resection. CONCLUSIONS: Conservative treatment with intravenous
      antibiotics can be used in uncomplicated cecal diverticulitis. Complicated cecal
      diverticulitis is managed surgically and the type of resection depends mainly on
      the extent of inflammation.

PMID- 25851945
TI  - Knowledge, Attitudes, and Practice Regarding Genetic Testing and Genetic
      Counselors in Jordan: A Population-Based Survey.
AB  - Genetic testing has a potential in the prevention of genetic diseases,
      particularly in communities with high rates of consanguineous marriage.
      Therefore, knowledge, practice, and attitudes of the public in Jordan regarding
      genetic testing were investigated. Individuals (N = 3,196) were questioned about
      the concepts of genetic testing and genetic counselors, if they underwent any
      genetic tests, the type of test, the method of consenting to the test, as well as
      their level of satisfaction with the privacy of the genetic testing service. The
      likelihood of pursuing predictive genetic testing for cancer was also
      investigated. Although almost 70 % of respondents knew the term "genetic
      testing," only 18 % had undergone genetic testing, primarily the mandatory
      premarital test. In addition, there was a lack of general knowledge about genetic
      counselors. Many of those who had genetic testing (45 %) indicated they did not
      go through a consent process, and a lack of consent was significantly related to
      dissatisfaction with the privacy of the service. Approximately 55 % of
      respondents indicated they would potentially pursue predictive genetic testing
      for cancer. Going for routine health checkups was not significantly correlated
      with either actual or potential uptake of genetic testing, suggesting health care
      providers do not play an influential role in patients' testing decisions. Our
      results show a gap between the knowledge and uptake of genetic testing and may
      help to guide the design of effective strategies to initiate successful genetic
      counseling and testing services.

PMID- 25851947
TI  - A call for statistical editors in ecology.

PMID- 25851948
TI  - Managing older adults with ground-level falls admitted to a trauma service: the
      effect of frailty.
AB  - OBJECTIVES: To determine whether frail elderly adults are at greater risk of
      fracture after a ground-level fall (GLF) than those who are not frail. DESIGN:
      Prospective observational study. SETTING: Level 1 trauma center. PARTICIPANTS:
      All elderly (>=65) adults presenting after a GLF over 1 year (N = 110; mean age
      +/- SD 79.5 +/- 8.3, 54% male). MEASUREMENT: A Frailty Index (FI) was calculated
      using 50 preadmission frailty variables. Participants with a FI of 0.25 or
      greater were considered to be frail. The primary outcome measure was a new
      fracture; 40.1% (n = 45) of participants presented with a new fracture. The
      secondary outcome was discharge to an institutional facility (rehabilitation
      center or skilled nursing facility). Multivariate logistic regression was
      performed. RESULTS: Forty-three (38.2%) participants were frail. The median
      Injury Severity Score was 14 (range 9-17), and the mean FI was 0.20 +/- 0.12.
      Frail participants were more likely than those who were not frail to have
      fractures (odds ratio (OR) = 1.8, 95% confidence interval (CI) = 1.2-2.3, P =
      .01). Thirty-six (32.7%) participants were discharged to an institutional
      facility. Frail participants were more likely to be discharged to an
      institutional facility (OR = 1.42, 95% CI = 1.08-3.09, P = .03) after a GLF.
      CONCLUSION: Frail individuals have a higher likelihood of fractures and discharge
      to an institutional facility after a GLF than those who are not frail. The FI may
      be used as an adjunct for decision-making when developing a discharge plan for an
      elderly adult after a GLF.

PMID- 25851949
TI  - PROVEAN web server: a tool to predict the functional effect of amino acid
      substitutions and indels.
AB  - We present a web server to predict the functional effect of single or multiple
      amino acid substitutions, insertions and deletions using the prediction tool
      PROVEAN. The server provides rapid analysis of protein variants from any
      organisms, and also supports high-throughput analysis for human and mouse
      variants at both the genomic and protein levels. AVAILABILITY AND IMPLEMENTATION:
      The web server is freely available and open to all users with no login
      requirements at http://provean.jcvi.org. CONTACT: achan@jcvi.org SUPPLEMENTARY
      INFORMATION: Supplementary data are available at Bioinformatics online.

PMID- 25851950
TI  - Characterization of a flavin-containing monooxygenase from Corynebacterium
      glutamicum and its application to production of indigo and indirubin.
AB  - OBJECTIVE: To examine the role of a gene encoding flavin-containing monooxygenase
      (cFMO) from Corynebacterium glutamicum ATCC13032 when cloned and expressed in
      Escherichia coli for the production of indigo pigments. RESULTS: The blue
      pigments produced by recombinant E. coli were identified as indigo and indirubin.
      The cFMO was purified as a fused form with maltose-binding protein (MBP). The
      enzyme was optimal at 25  degrees C and pH 8. From absorption spectrum analysis,
      the cFMO was classified as a flavoprotein. FMO activity was strongly inhibited by
      1 mM Cu(2+) and recovered by adding 1-10 mM EDTA. The enzyme catalyzed the
      oxidation of TMA, thiourea, and cysteamine, but not glutathione or cysteine. MBP
      cFMO had an indole oxygenase activity through oxygenation of indole to indoxyl.
      The recombinant E. coli produced 685 mg indigo l(-1) and 103 mg indirubin l(-1)
      from 2.5 g L-tryptophan l(-1). CONCLUSION: The results suggest the cFMO can be
      used for the microbial production of both indigo and indirubin.

PMID- 25851951
TI  - Activin A can induce definitive endoderm differentiation from human
      parthenogenetic embryonic stem cells.
AB  - OBJECTIVES: As activin/nodal signaling plays a key role in definitive endoderm
      (DE) differentiation, we have explored activin A-induced differentiation of DE
      from human parthenogenetic embryonic stem cells (hPESCs). RESULTS: Administration
      of 5 ng activin A/ml had no effect on the expression of markers of DE
      differentiation. However, higher concentrations of activin A (50 and 100 ng/ml)
      upregulated Sox17 and Cxcr4, as well upregulating the mesendodermal precursor
      marker, Brachyury. CONCLUSIONS: These findings demonstrate that low dose activin
      A can maintain the undifferentiated potency of hPESCs, whereas higher doses
      induce DE differentiation; 50 ng/ml is the optimal concentration for inducing DE
      from hPESCs.

PMID- 25851952
TI  - Enzymatic synthesis of aroma acetoin fatty acid esters by immobilized Candida
      antarctica lipase B.
AB  - OBJECTIVE: To enzymatically synthesize aroma acetoin fatty acid esters, useful as
      flavor and fragrance ingredients in foods. RESULTS: Immobilized Candida
      antarctica lipase B (CALB), performed significantly better than lipases from
      Rhizopus niveus and Candida rugosa in carrying out the esterification of acetoin
      and fatty acids. C4-C12 straight chain fatty acids were suitable acyl donors and
      CALB had a strong preference for longer straight chains up to ten carbon atoms.
      Higher temperatures, 40-60  degrees C, and higher acetoin/fatty acid molar ratios
      favored the conversion. The maximum yield of acetoin octanoate obtained was (51
      +/- 1) % after 24 h reaction time in hexane with 0.25 M octanoic acid, 5:1 excess
      acetoin and an enzyme concentration of 6 g/mol fatty acid at 60  degrees C. The
      enzyme activity declined at a steady rate during reuse at 60  degrees C and after
      the 10th cycle, 65 % of initial activity was still be retained. CONCLUSION: This
      is the first report of acetoin fatty acid ester synthesis by biological method
      and CALB has been shown to be effective for the lipase-catalyzed esterification
      of acetion and C4-C12 straight chain fatty acids.

PMID- 25851953
TI  - Whole genome sequences in pulse crops: a global community resource to expedite
      translational genomics and knowledge-based crop improvement.
AB  - Unprecedented developments in legume genomics over the last decade have resulted
      in the acquisition of a wide range of modern genomic resources to underpin
      genetic improvement of grain legumes. The genome enabled insights direct
      investigators in various ways that primarily include unearthing novel structural
      variations, retrieving the lost genetic diversity, introducing novel/exotic
      alleles from wider gene pools, finely resolving the complex quantitative traits
      and so forth. To this end, ready availability of cost-efficient and high-density
      genotyping assays allows genome wide prediction to be increasingly recognized as
      the key selection criterion in crop breeding. Further, the high-dimensional
      measurements of agronomically significant phenotypes obtained by using new
      generation screening techniques will empower reference based resequencing as well
      as allele mining and trait mapping methods to comprehensively associate genome
      diversity with the phenome scale variation. Besides stimulating the forward
      genetic systems, accessibility to precisely delineated genomic segments reveals
      novel candidates for reverse genetic techniques like targeted genome editing. The
      shifting paradigm in plant genomics in turn necessitates optimization of crop
      breeding strategies to enable the most efficient integration of advanced omics
      knowledge and tools. We anticipate that the crop improvement schemes will be
      bolstered remarkably with rational deployment of these genome-guided approaches,
      ultimately resulting in expanded plant breeding capacities and improved crop
      performance. 

PMID- 25851954
TI  - Efficient and simple electro-transformation of intact cells for the
      basidiomycetous fungus Pseudozyma hubeiensis.
AB  - OBJECTIVE: An electroporation procedure for the species was investigated to
      develop an efficient transformation method for the basidiomycetous fungus
      Pseudozyma hubeiensis SY62, a strong biosurfactant-producing host. RESULTS: A
      plasmid, pUXV1emgfp including green fluorescence protein as a reporter gene, was
      constructed to determine the transformation and expression of foreign genes.
      Optimal electroporation conditions achieved 44.8 transformants MUg(-1) plasmid
      competency (intact cells) without protoplast treatment. Lithium acetate
      treatments increased the efficiency to approx. Twice that of control experiments.
      Almost all transformants demonstrated green fluorescence expressed in the
      transformant cells. CONCLUSION: The optimal method, successfully applied to
      several related species, yields sufficient transformant colonies to engineer the
      host strain.

PMID- 25851955
TI  - Assessing the treatment effect in a randomized controlled trial with extensive
      non-adherence: the EVOLVE trial.
AB  - Intention-to-treat (ITT) analysis is widely used to establish efficacy in
      randomized clinical trials. However, in a long-term outcomes study where non
      adherence to study drug is substantial, the on-treatment effect of the study drug
      may be underestimated using the ITT analysis. The analyses presented herein are
      from the EVOLVE trial, a double-blind, placebo-controlled, event-driven
      cardiovascular outcomes study conducted to assess whether a treatment regimen
      including cinacalcet compared with placebo in addition to other conventional
      therapies reduces the risk of mortality and major cardiovascular events in
      patients receiving hemodialysis with secondary hyperparathyroidism. Pre-specified
      sensitivity analyses were performed to assess the impact of non-adherence on the
      estimated effect of cinacalcet. These analyses included lag-censoring, inverse
      probability of censoring weights (IPCW), rank preserving structural failure time
      model (RPSFTM) and iterative parameter estimation (IPE). The relative hazard
      (cinacalcet versus placebo) of mortality and major cardiovascular events was 0.93
      (95% confidence interval 0.85, 1.02) using the ITT analysis; 0.85 (0.76, 0.95)
      using lag-censoring analysis; 0.81 (0.70, 0.92) using IPCW; 0.85 (0.66, 1.04)
      using RPSFTM and 0.85 (0.75, 0.96) using IPE. These analyses, while not providing
      definitive evidence, suggest that the intervention may have an effect while
      subjects are receiving treatment. The ITT method remains the established method
      to evaluate efficacy of a new treatment; however, additional analyses should be
      considered to assess the on-treatment effect when substantial non-adherence to
      study drug is expected or observed.

PMID- 25851957
TI  - Paternal Transmission of a Secondary Symbiont during Mating in the Viviparous
      Tsetse Fly.
AB  - Sodalis glossinidius, a maternally inherited secondary symbiont of the tsetse
      fly, is a bacterium in the early/intermediate state of the transition toward
      symbiosis, representing an important model for investigating establishment and
      evolution of insect-bacteria symbiosis. The absence of phylogenetic congruence in
      tsetse-Sodalis coevolution and the existence of Sodalis genotypic diversity in
      field flies are suggestive for a horizontal transmission route. However, to date
      no natural mechanism for the horizontal transfer of this symbiont has been
      identified. Using novel methodologies for the stable fluorescent-labeling and
      introduction of modified Sodalis in tsetse flies, we unambiguously show that male
      borne Sodalis is 1) horizontally transferred to females during mating and 2)
      subsequently vertically transmitted to the progeny, that is, paternal
      transmission. This mixed mode of transmission has major consequences regarding
      Sodalis' genome evolution as it can lead to coinfections creating opportunities
      for lateral gene transfer which in turn could affect the interaction with the
      tsetse host. 

PMID- 25851958
TI  - New Genetic Evidence Resolves Origins of Modern Japanese.

PMID- 25851956
TI  - Adaptive Modifications of Muscle Phenotype in High-Altitude Deer Mice Are
      Associated with Evolved Changes in Gene Regulation.
AB  - At high-altitude, small mammals are faced with the energetic challenge of
      sustaining thermogenesis and aerobic exercise in spite of the reduced O2
      availability. Under conditions of hypoxic cold stress, metabolic demands of
      shivering thermogenesis and locomotion may require enhancements in the oxidative
      capacity and O2 diffusion capacity of skeletal muscle to compensate for the
      diminished tissue O2 supply. We used common-garden experiments involving highland
      and lowland deer mice (Peromyscus maniculatus) to investigate the transcriptional
      underpinnings of genetically based population differences and plasticity in
      muscle phenotype. We tested highland and lowland mice that were sampled in their
      native environments as well as lab-raised F1 progeny of wild-caught mice.
      Experiments revealed that highland natives had consistently greater oxidative
      fiber density and capillarity in the gastrocnemius muscle. RNA sequencing
      analyses revealed population differences in transcript abundance for 68 genes
      that clustered into two discrete transcriptional modules, and a large suite of
      transcripts (589 genes) with plastic expression patterns that clustered into five
      modules. The expression of two transcriptional modules was correlated with the
      oxidative phenotype and capillarity of the muscle, and these phenotype-associated
      modules were enriched for genes involved in energy metabolism, muscle plasticity,
      vascular development, and cell stress response. Although most of the individual
      transcripts that were differentially expressed between populations were
      negatively correlated with muscle phenotype, several genes involved in energy
      metabolism (e.g., Ckmt1, Ehhadh, Acaa1a) and angiogenesis (Notch4) were more
      highly expressed in highlanders, and the regulators of mitochondrial biogenesis,
      PGC-1alpha (Ppargc1a) and mitochondrial transcription factor A (Tfam), were
      positively correlated with muscle oxidative phenotype. These results suggest that
      evolved population differences in the oxidative capacity and capillarity of
      skeletal muscle involved expression changes in a small suite of coregulated
      genes. 

PMID- 25851959
TI  - Real-time teleophthalmology in rural Western Australia.
AB  - OBJECTIVE: This study aims to assess the current utilisation of a real-time
      teleophthalmology service for rural Western Australia (WA). DESIGN: Service
      evaluation by prospective audit. SETTING: Includes general practices,
      optometrists, hospitals in rural WA and the Lions Eye Institute in Perth.
      PARTICIPANTS: Eighty-five patients from rural WA participating. INTERVENTIONS:
      Video consultation (VC) with a general ophthalmologist. MAIN OUTCOME MEASURES:
      Number of referring practitioners and their locations, software and imaging
      equipment used as well as the presentation, working diagnosis and follow-up plan
      for each consultation. RESULTS: Eighty-five participants took part in a total of
      100 VCs in the 5-month data collection period. There were 49 men (58%); age range
      7-92 years; 31 identified as Indigenous Australian (37%). Participants were
      referred by optometrists (59%), hospital district medical officers (23%) and GPs
      (18%). Karratha (41%), Albany (20%) and Broome (14%) were the main VC locations.
      There were 31 different eye conditions managed; red eye, acute vision loss, known
      glaucoma and abnormal retinal photographs were the main presentations. Skype was
      the commonly used software (71%). Images were provided in 63% of all VCs. The
      main equipment used included digital retinal cameras (56%), smartphones (25%) and
      digital slit lamps (13%). An outpatient appointment with the ophthalmologist was
      recommended following 35 VCs. CONCLUSIONS: Optometrists used this service most
      frequently, despite a lack of financial incentive. Digital retinal cameras and
      smartphones were the most commonly used imaging modalities. Overall, real-time
      teleophthalmology was used in the management of a broad range of eye conditions
      and was a useful supplement to outreach ophthalmology services.

PMID- 25851960
TI  - Use of narrow-diameter implants in the posterior jaw: a systematic review.
AB  - STATEMENT OF PROBLEM: Evidence is limited on the efficacy of narrow-diameter
      implants (NDIs) in the posterior jaw. PURPOSE: The purpose of this systematic
      review was to assess the survival of NDIs and provide guidelines for their safe
      use. MATERIALS AND METHODS: Electronic search of the English-language literature
      enriched by hand search to identify suitable publications was made. Only peer
      reviewed clinical studies published from January 1990 through March 2014 were
      included. RESULTS: Seventeen studies with a total of 1644 implants met the
      inclusion criteria, with an observation period from 1 up to 12 years. The mean
      survival rate of 98.6% was reported. Technical and other complications were
      observed. CONCLUSION: Short-term clinical data suggest that NDIs may serve in the
      posterior jaw as an alternative to standard-diameter implants. However, certain
      clinical conditions must be observed to assure long-term success.

PMID- 25851961
TI  - Successful emergency combined therapy with partial splenic arterial embolization
      and endoscopic injection therapy against a bleeding duodenal varix in a child.
AB  - There is no consensus guidelines for treating duodenal variceal bleeding, which
      is a rare and life-threatening complication of portal hypertension. Here we
      report an exceedingly unusual case in a 9-year-old boy who had developed left
      sided portal hypertension after surgical treatment for pancreatoblastoma followed
      by a duodenal variceal bleeding with massive melena, severe anemia (hemoglobin
      4.5 g/dL) and hypovolemic shock. Emergency partial splenic arterial embolization
      (PSE) provided a reduction of variceal bleeding and improved blood pressure.
      Endoscopic injection sclerotherapy (EIS) was subsequently performed and stopped
      the duodenal variceal bleeding without the complication of portal vein thrombosis
      caused by injected sclerosant under hepatopetal flow. Our case demonstrates that
      emergency combined therapy with PSE and EIS can be considered as the therapeutic
      option for the management of left-sided portal hypertension-induced ectopic
      variceal bleedings in order to avoid the complication of portal embolization by
      EIS and provide effective hematostasis. 

PMID- 25851962
TI  - Mechanism of DNA assembly as revealed by energy barriers.
AB  - The mechanism of DNA assembly is revealed by analyzing the energy barriers during
      nucleation and growth. The assembly is controlled by two competing parameters:
      the conformation adjustment rate of DNA strands and the spreading rate of new
      strands on the nuclei surface, both of which are temperature dependent and can be
      tuned by sequence design. 

PMID- 25851963
TI  - An unusual presentation of erythema multiforme in a paediatric patient.
AB  - BACKGROUND: Erythema multiforme (EM) is an acute, vesiculobullous disease of skin
      and mucous membranes with symptoms ranging from mild to severe. A complex
      interaction of different factors has been implicated the condition; the majority
      with a preceding herpes simplex infection. This report describes an unusual
      presentation of erythema multiforme affecting the lips and oral mucosa of a
      healthy 7-year-old boy in the form of lip adherence. CASE REPORT: Two weeks
      following eruption of oral ulcerations, a 7-year-old healthy boy developed severe
      erosive ulceration of both lips, causing complete lip adherence. This was
      accompanied by marked bilateral submandibular and cervical lymphadenopathy,
      tremor and sweating. Clinical and laboratory investigations led to a diagnosis of
      erythema multiforme. The patient was treated initially with gentle application of
      Vaseline between the lips using cotton buds in an attempt to release lip
      adhesion, followed by surgical release of the lips under general anaesthesia.
      Analgesics and topical steroid mouthwash were provided. FOLLOW-UP: Seven months
      later, the patient presented with a recurrence of his EM which included lesions
      on the skin. The patient was treated with antivirals, topical and systematic
      steroids to suppress the recurrent attacks of EM. Eighteen months following the
      initial presentation the patient and parent reported considerable decrease in the
      frequency, severity and duration of the occurrence of intra-oral ulcers, with no
      major episode of target lesions on the skin. CONCLUSION: Erythema multiforme is
      rare in children, however it should be considered in the differential diagnosis
      of recurrent erosive oral ulcerative lesions especially when the oral lesions
      resemble those of primary herpetic gingivostomatitis.

PMID- 25851964
TI  - Maternal attitudes towards tooth decay in children aged 12-18 months in Pelotas,
      Brazil.
AB  - AIM: This was to assess mothers' attitudes towards dental caries in children aged
      12-18 months. METHODS: This study targeted mothers of children aged 12-18 months.
      Data about demographic and socioeconomic status were collected by interviews with
      each mother. In addition, the mother was asked about her attitudes regarding
      caries in her child's primary teeth. A dental examination of each child was also
      conducted. Chi-square, bivariate, and multiple logistic regression analyses were
      performed. RESULTS: A total of 262 mother-child pairs were included, and 18.7 %
      of the children had dental caries. If a child presented with dental caries in
      their primary teeth, 93.5 % of the mothers reported that they would take the
      child to a dentist. Mothers who had only one child and those who had children
      with dental caries were more likely to report that they did not expect primary
      dental caries treatment by the dentist. CONCLUSION: Most mothers reported that
      they would take their children to a dentist when they presented with dental
      caries. Despite this positive result, educational measures should continue to be
      emphasised, especially among mothers of children at a higher risk of caries and
      among first-time mothers.

PMID- 25851966
TI  - Older people living alone at home with terminal cancer.
AB  - This study describes the lived experiences of older people coping with terminal
      cancer and living alone, focusing on how they face challenges of the biographical
      life changes from their disease progression. Face-to-face semi-structured
      interviews were conducted in two phases with palliative care clients of a
      community-based service in Western Australia (2009-2011): Brief interviews with
      43 cancer patients who live alone and then in-depth interviews with 8 of them.
      Using biographical disruption as the analytical framework for interpreting the
      qualitative data, four main themes emerged: Biographical disruption: adjusting to
      change; Biographical continuity: preserving normality; Biographical
      reconstruction: redefining normality; and Biographical closure: facing the end.
      Biographical disruption was a suitable framework for analysis, permitting
      identification of the biographical disruptions of the individual's world and the
      reframing that is undertaken by the individual to maintain autonomy and
      independence while acknowledging and accepting their closeness to death.
      Understanding the factors associated with the individual's need to maintain their
      own identity will enable nurses working with this population to tailor support
      plans that meet the individuals' needs while maintaining or restoring the
      person's sense of self. Interventions that directly address end-of-life suffering
      and bolster sense of dignity and personhood need to be considered. 

PMID- 25851968
TI  - [The pathogenesis of Ebola virus disease].

PMID- 25851967
TI  - Evaluation of advanced multiplex short tandem repeat systems in pairwise kinship
      analysis.
AB  - The AmpFLSTR Identifiler Kit, comprising 15 autosomal short tandem repeat (STR)
      loci, is commonly employed in forensic practice for calculating match
      probabilities and parentage testing. The conventional system exhibits
      insufficient estimation for kinship analysis such as sibship testing because of
      shortness of examined loci. This study evaluated the power of the PowerPlex
      Fusion System, GlobalFiler Kit, and PowerPlex 21 System, which comprise more than
      20 autosomal STR loci, to estimate pairwise blood relatedness (i.e., parent
      child, full siblings, second-degree relatives, and first cousins). The genotypes
      of all 24 STR loci in 10,000 putative pedigrees were constructed by simulation.
      The likelihood ratio for each locus was calculated from joint probabilities for
      relatives and non-relatives. The combined likelihood ratio was calculated
      according to the product rule. The addition of STR loci improved separation
      between relatives and non-relatives. However, these systems were less effectively
      extended to the inference for first cousins. In conclusion, these advanced
      systems will be useful in forensic personal identification, especially in the
      evaluation of full siblings and second-degree relatives. Moreover, the additional
      loci may give rise to two major issues of more frequent mutational events and
      several pairs of linked loci on the same chromosome. 

PMID- 25851969
TI  - [How to improve the diagnosis rate of early gastric cancer in China].
AB  - China has great burden of gastric cancer, and the diagnosis rate of early gastric
      cancer is relatively low (<10%). To perform screening, early endoscopic diagnosis
      and treatment of gastric cancer in high-risk population is a feasible and
      efficient way to change the current status. Therefore, the Chinese Society of
      Digestive Endoscopy recently issued Consensus on screening, "Endoscopic diagnosis
      and treatment of early gastric cancer screening in China". The consensus suggests
      a feasible and efficient strategy for early detection of gastric cancer:
      screening with non-invasive procedures, followed by intensive endoscopic
      examination for screened high-risk population. In this article, we also describe
      the current status, the causes, high-risk population and early diagnosis of
      gastric cancer in China; and review the new development of serology and
      endoscopic techniques for early diagnosis.

PMID- 25851970
TI  - [Efficacy of epigallocatechin gallate in treatment of alkali burn injury of
      murine cornea].
AB  - OBJECTIVE: To evaluate the efficacy of epigallocatechin gallate (EGCG) in
      treatment of corneal alkali burn injury in mice. METHODS: Corneal alkali burn
      injury was induced by sodium hydroxide method in C57BL/6J mice. The mice with
      cornea burns were treated intraperitoneally with EGCG solution or phosphate
      buffer solution (PBS) respectively. The healing of corneal epithelium, the
      formation of corneal neovascularization (CNV) and the inflammation reaction were
      assessed by slit -lamp microscopy and histological examination. Expression of
      vascular endothelial growth factor (VEGF) mRNA and protein in cornea was
      evaluated by real -time reverse transcription polymerase chain reaction (RT-PCR)
      and immunohistochemistry, respectively. Myeloperoxidase (MPO) assay was used to
      quantitatively evaluate the polymorphonuclear neutrophils (PMNs) infiltration in
      the corneas. RESULTS: The healing rate of corneal epithelium in EGCG group was
      significantly higher than that of PBS group at d1, d3 and d7 after treatment (d1:
      41.0%+/-13.0% vs 23.8%+/-7.6%; d3: 76.6%+/-7.5% vs 61.2%+/-6.8%; d7: 87.8%+/-8.5%
      vs 74.0%+/-9.1%; all P <0.05). The CNV scores and the number of CNV in the
      corneal sections of EGCG group were significantly lower than those of PBS group
      at d3, d7 and d14 after treatment (CNV score: d3: 1.1+/-0.5 vs 6.6+/-1.0; d7:
      1.3+/-0. 3 vs 8.1+/-1.0; d14: 0.9+/-0.2 vs 9.2+/-1.1; CNV number: d3: 1.68+/-0.61
      vs 2.92+/-0.95; d7: 4.80+/-1.36 vs 7.92+/-1.28; d14: 3.64+/-0.71 vs 5.88+/-0.76;
      all P<0.05) . The expression of VEGF protein at d3 (0.19+/-0.05 vs 0.45+/-0.08)
      and d7 (0.42+/-0.07 vs 0.84+/-0.09), the expression of VEGF mRNA at d1, d3 and d7
      in EGCG group were significantly lower than those in PBS group (all P <0.05).
      Compared to PBS group, the inflammatory index at d3 (3.2+/-0.4 vs 3.7+/-0.5) and
      d7 (2.3+/-0.5 vs 4.0+/-0.0), the number of PMNs in the corneal sections and the
      MPO values at d3, d7 and d14 in EGCG group were significantly decreased (PMNs:
      d3: 34.5+/-15.7 vs 90.0+/-28.8; d7: 17.1+/-11.4 vs 54.9+/-25.9; d14: 12. 8+/-4.6
      vs 39.0+/-17.9; all P <0.05). CONCLUSION: In the murine corneal alkali burn
      model, intraperitoneal injection of EGCG solution can promote the healing of
      corneal epithelium, inhibit the formation of CNV and reduce the inflammatory cell
      infiltration in the corneas.

PMID- 25851971
TI  - [Protective effect of grape seed proanthocyanidin on cultured RGC-5 cells against
      CoCl2-induced hypoxic injury].
AB  - OBJECTIVE: To investigate the protective effects of grape seed proanthocyanidin
      extracts (GSPE) against CoCl2-induced hypoxic injury in cultured RGC-5 cells.
      METHODS: CoCl2(400 MUmol/L) was used to induce hypoxic injury in cultured RGC-5
      cells; the cells were pretreated with 0,100,200,400 and 800MUmol/L GSPE for 24h.
      The cell viability was assayed by MTT; the apoptosis was detected by Hoechst
      33342 staining; the intracellular reactive oxygen species (ROS) was measured by
      H2DCFDA oxidative reaction. The mRNA expression of Bcl-2, caspase 9 and caspase 3
      was determined by real-time PCR. RESULTS: Compared to hypoxic control group,
      pretreatment with GSPE significantly increased viability of RGC-5 cells
      (P<0.001), reduced cell apoptosis (P<0 .001) and intracellular ROS(P <0 .001). In
      addition, GSPE significantly increased the mRNA expression of Bcl-2(P<0 .001) and
      decreased mRNA expression of caspase 9(P<0 .001) and caspase 3(P<0 .001) compared
      to hypoxic control group. CONCLUSION: GSPE may have a protective effect against
      CoCl2-induced hypoxic injury in cultured RGC-5 cells. The decrease of
      intercellular ROS, up-regulation of Bcl-2 and down-regulation of caspase 9 and
      caspase 3 may be involved in the mechanism of the protective effect of GSPE.

PMID- 25851972
TI  - [Neuroprotective effects of paeonol in a cell model of Parkinson disease].
AB  - OBJECTIVE: To investigate the effects of paeonol on neuron cell model of
      Parkinson disease (PD). METHODS: The cell model of Parkinson disease was induced
      by treatment of 1-Methyl-4-phenylpyridinium (MPP+) in PC12 cells, the PD model
      cells were treated with 1 MUmol/L, 3 MUmol/L or 9 MUmol/L paeonol for 24h,
      respectively. Cell viability and LDH leakage were detected by MTT and lactate
      dehydrogenase (LDH) assay; the apoptosis of PC12 cells was assessed by Hoechst
      33258 staining and flow cytometry; reactive oxygen species (ROS) production was
      detected by DCFH-DA method; and the ratio of Bax/Bcl-2 and activation of caspase
      3 were determined by Western blotting. RESULTS: MPP+ treatment significantly
      reduced cell viability, increased LDH leakage, enhanced the proportion of
      apoptotic cells and ROS production. In addition, MPP+ treatment dramatically
      increased the Bax/Bcl-2 ratio, and the activation of caspase-3. Compared to PD
      model group, paeonol treatment significantly enhanced cell viability, decreased
      LDH leakage, inhibited the proportion of apoptotic cells and ROS production,
      reduced the Bax/Bcl-2 ratio and the activated caspase-3 protein. CONCLUSION:
      Paeonol can prevent PC12 cells from apoptosis induced by MPP+, and the mechanism
      may be associated with the down-regulation of ROS production, Bax/Bcl-2 ratio and
      Caspase-3 activation.

PMID- 25851973
TI  - [Effect of licorice flavonoids on kainic acid-induced seizure in mice].
AB  - OBJECTIVE: To investigate the effect of licorice flavonoid (LF) on kainic acid
      (KA)-induced seizure in mice and its mechanism. METHODS: Male adult ICR mice were
      injected with 25 mg/kg KA to induce temporal lobe seizure. LF was administrated 7
      d before seizure induction (pre-treatment) or 24 h after seizure induction (post
      treatment) for 7 d. Acute seizure latency, seizure stage and duration were
      observed and compared between LF- and vehicle-treated mice. From d2 on, mice with
      status epilepticus were video-monitored for spontaneous seizures, 10 h/d for 6 w.
      Immunohistochemical analysis of BrdU and Timm staining was conducted to detect
      the neurogenesis and mossy fiber sprouting, respectively. RESULTS: No significant
      difference was observed in acute seizure latency, seizure stage and duration
      between LF-and vehicle-treated mice. KA-induced acute seizure resulted in
      spontaneous seizure in mice, and the seizure frequency was increased with time.
      Pre- and post-treatment with LF decreased seizure frequency from w3 after
      modeling [(0.58+/-0.15)/d, (0.38+/-0.38)/d vs (1.23+/-0.23)/d, P <0.05].
      Furthermore, KA-induced seizure resulted in robust neurogenesis and mossy fiber
      sprouting, while treatment with LF both pre- and post- KA injection significantly
      inhibited neurogenesis (15.6+/-2.6, 17.1+/-3.1 vs 28.9+/-3.5, P <0.05) and mossy
      fiber sprouting (1.33+/-0.31, 1.56+/-0.42 vs 3.0+/-0.37, P <0.05). CONCLUSION: LF
      has no significant anti-seizure effect. However, it can decrease epileptogenesis
      through inhibition of neurogenesis and mossy fiber sprouting.

PMID- 25851974
TI  - [Treatment of rheumatoid arthritis with flavonoids of Echinps latifolius Tausch
      in rat model].
AB  - OBJECTIVE: To investigate the effect of Flavonoids extracted from Echinps
      latifolius Tausch(FELT) on rheumatoid arthritis (RA) in rat model. METHOD: Fifty
      SD rats were randomly divided into model group, control group, and low, medium,
      and high-dose FELT groups (n=10 in each group). Complete Freund's adjuvant (0.1
      mL) was used to induce RA in rats. FELT in doses of 50 mg/kg, 100 mg/kg, 150
      mg/kg was given to rats in low, medium and high-dose FELT groups by gavage, and
      same volume of PBS was given to rats in control group. The arthritis score and
      the paw swelling score were measured to evaluate the therapeutic effect of FELT.
      Real time qPCR was used to detect the mRNA expression of fibronectin and MMP3 in
      synovial tissue and the mRNA expression of caspase 3, Bcl-2 and Bcl-2 associated
      X protein (Bax) in fibroblast-like synoviocytes (FLS). RESULTS: The arthritis
      score and the paw swelling score were significantly decreased in three FELT
      groups compared to RA model rats (P <0.05). The relative expression levels of FN
      and MMP3 mRNA in synovium of three FELT-treatment groups were significantly lower
      than those in model group (1.80, 1.76 and 1.67 vs 2.53; 1.69, 1.46 and 1.45 vs
      2.67, respectively, all P <0.05). The relative expression levels of Bax and
      caspase 3 mRNA in FLSs of three FELT groups were higher than those in model group
      (0.56, 0.58 and 0.60 vs 0.30; 0.54, 0.56 and 0.59 vs 0.29, respectively, all P
      <0.05); while the relative expression levels of Bcl-2 mRNA in FELT groups were
      lower than that in model group (2.20, 2.08 and 2.08 vs 4.04, respectively, P
      <0.05). CONCLUSION: FELT may inhibit the synovium proliferation in RA model rats
      through promoting the FLS apoptosis.

PMID- 25851975
TI  - [Hypouricemic effect of ethanol extracts from Dioscoreae Nipponicae Rhizoma].
AB  - OBJECTIVE: To investigate the effect of ethanol extracts from Dioscoreae
      Nipponicae Rhizoma on hyperuricemic mice. METHODS: The hyperuricemia was induced
      by gavage of hypoxanthine and subcutaneous injection of potassium oxonate (model
      A) or subcutaneous injection of uric acid (model B) in ICR male mice. The mice in
      ethanol extracts groups were administrated with Dioscoreae Nipponicae Rhizoma
      ethanol extracts 5.4 g/kg by gavage, the positive control groups were given with
      10 mg/ml allopurinol or 5 mg/ml benzbromarone by gavage, respectively. The plasma
      uric acid levels were measured by using HPLC. RESULTS: The plasma uric acid
      levels of model group, control group and ethanol extract group in model A mice
      were (40.03+/-27.24), (4.08+/-1.47) and (18.10+/-8.87) g/mL (compared with model
      group, P <0.05), respectively. The plasma uric acid levels of model group,
      control group and ethanol extract group in model B mice were (18.57+/-3.83),
      (4.29+/-2.36) and (15.36+/-2.71) g/mL (compared with model group, P <0.05),
      respectively. CONCLUSION: The ethanol extracts from Dioscoreae Nipponicae Rhizoma
      have certain hypouricemic effect in hyperuricemic mice induced by hypoxanthine
      and potassium oxonate or by uric acid.

PMID- 25851976
TI  - [Factors related to therapeutic outcomes of intravenous thrombolysis in stroke
      patients with different severity].
AB  - OBJECTIVE: To investigate the factors related to therapeutic outcomes of
      intravenous thrombolysis in patients with acute ischemic stroke (AIS) of
      different severity. METHODS: Clinical data of patients with AIS treated with
      intravenous thrombolysis in the Second Affiliated Hospital, Zhejiang University
      School of Medicine between June 2009 and December 2013 were retrospectively
      reviewed. According to National Institutes of Health Stroke Scale (NIHSS),
      patients were categorized as mild stroke (<=8, n=134), moderate stroke (9-15,
      n=121) and severe stroke(>=16, n=110). The good outcome was defined as modified
      Rankin Scale <= 2. The factors related to functional outcomes and hemorrhagic
      transformation (HT) were analyzed and compared among 3 groups. RESULTS: Among 365
      enrolled patients, good outcomes in 3 groups were 78.4% (105/134), 47.9% (58/121)
      and 24.5%(27/110), respectively. In patients with mild stroke, age (OR=0.937,
      95%CI: 0.898-0.978; P=0.003), baseline NIHSS (OR=0.732, 95%CI:0.564-0.950;
      P=0.019), onset to needle time (ONT) within 270 min (OR=4.109, 95%CI:1.441
      11.719; P=0.008) independently predicted good outcome, while baseline glucose
      (OR=1.326, 95%CI:1.009-1.743; P=0.043) was independently associated with
      parenchymal hematoma (PH). In patients with moderate stroke, age (OR=0.954,
      95%CI: 0.924-0.984; P=0.003) and baseline NIHSS (OR=0.760, 95%CI: 0.619-0.933;
      P=0.009) independently predicted good outcome, while atrial fibrillation
      (OR=3.307, 95%CI: 1.140~9.596; P=0.028) and systolic pressure (OR=0.967, 95%CI:
      0.943~0.991; P=0.008) was independently associated with hemorrhagic infaction.
      Atrial fibrillation (OR=36.972, 95%CI: 1.770-772.462; P=0.02) was independently
      associated with PH. In patients with severe stroke, baseline NIHSS (OR=0.808,
      95%CI:0.677-0.963; P=0.018) independently predicted good outcome, while no
      independent risk factors of HT was found. CONCLUSION: For different severity of
      AIS patients, the related factors of functional outcome and HT after thrombolysis
      were different.

PMID- 25851977
TI  - [Nutritional status in acute stage ischemic stroke and its relation to disease
      severity and prognosis of patients].
AB  - OBJECTIVE: To investigate the nutritional status in acute stage ischemic stroke
      and its relation to disease severity and prognosis of patients. METHODS: Fifty
      patients with ischemic stroke were admitted in hospital within 48 h after onset.
      National Institute of Health stroke scale (NIHSS) was used to assess the severity
      of stroke. Physical index and laboratory index were measured on d1, d7 and d14
      after admission. Physical index included body weight, body mass index, triceps
      skin folds, upper arm circumference and arm muscle circumference. Laboratory
      index included prealbumin, high sensitivity C-reactive protein (hs-CRP),
      complement C3 and cortisol. The severity of metabolic disturbance was expressed
      as the difference of biochemical indexes between the d7 and d1. All cases were
      followed up for 6 months. The prognosis of stroke was evaluated with modified
      Rankin (mRankin) scores. RESULTS: No significant changes of physical indexes were
      found between d7 and d1. The levels of prealbumin and complement C3 on d7 after
      admission were significantly decreased compared to d1 (198.8 mg/L+/-20.3 mg/L vs
      286.7 mg/L+/-23.8 mg/L and 0.6 g/L+/-0.1 g/L vs 1.0 g/L+/-0.1 g/L, respectively,
      both P<0.05). The levels of hs-CRP and cortisol at d7 were significantly
      increased compared to d1 (495.2 nmol/L+/-39.5 nmol/L vs 24.1 mg/L+/-5.2 mg/L and
      396.4 nmol/L+/-41.3 nmol/L vs 5.1 mg/L+/-1.2 mg/L, respectively, both P<0.05). On
      d14 after admission hs-CRP (13.2 mg/L+/-4.5 mg/L) and cortisol levels (463.4
      nmol/L+/-32.1 nmol/L) were still significantly higher than d1 (both P<0.05).
      However, there were no difference in prealbumin (259.2 mg/L+/-22.8 mg/L) and
      complement C3 (0.8 g/L+/-0.2 g/L) levels between d1 and d14 after admission.
      Correlation analysis revealed that the NIHSS scores and mRankin scores were
      correlated with nutrition metabolism disturbances (P<0.05). CONCLUSION: Nutrition
      metabolism disturbances in patients with acute ischemic stroke are related to the
      disease duration, the severity and prognosis of stroke.

PMID- 25851978
TI  - [Inhibition of gap junctional intercellular communication protects astrocytes
      from hypoxia/reoxygenation injury].
AB  - OBJECTIVE: To investigate the effects of inhibiting gap junctional intercellular
      communication on hypoxia/reoxygenation injury in astrocytes. METHODS: Primary
      cultured cerebral cortical astrocytes of neonate rats were divided into normal
      control group, hypoxia reoxygenation injury group and 18-alpha-glycyrrhetinic
      acid and oleamide (gap junctional intercellular channel inhibitors) group. The
      gap junction intercellular communication was determined by Parachute assay. The
      viability of astrocyes was detected by MTT assay. The apoptosis of astrocytes
      were detected with annexin V/PI and Hoechst 33258 staining. RESULTS: Compared
      with the normal control group, the gap junctional function of astrocytes was
      increased significantly in ischemia/reperfusion group (P<0.01), the surviving
      fraction of astrocytes decreased significantly (P<0.01) and its cell apoptosis
      ratio increased significantly (P<0.01). Compared with the ischemia/reperfusion
      group, the gap junctional function of astrocytes in18-alpha-glycyrrhetinic acid
      and oleamide group decreased significantly (P<0.01), the viability of astrocytes
      increased significantly (P<0.01), while cell apoptosis decreased significantly
      (P<0.01). CONCLUSION: Inhibition of intercellular gap junction has protective
      effect against hypoxia/reoxygenation injury in astrocytes.

PMID- 25851979
TI  - [Laparoscopic anti-reflux surgery with biological mesh in treatment of
      gastroesophageal reflux disease].
AB  - OBJECTIVE: To evaluate the application of biological mesh in laparoscopic anti
      reflux procedure for gastroesophageal reflux disease (GERD). METHODS: The
      clinical data of 20 consecutive GERD patients underwent anti-reflux surgery in
      Sir Run Run Shaw Hospital from December 2012 to April 2014 were retrospectively
      analyzed. The laparoscopic hiatal repair with 360 fundoplicaiton was performed
      and the biological mesh (BiodesignTM, Surgsis) was implanted for reinforcement of
      hiatal repair. RESULTS: All laparoscopic procedures were successful, no
      conversion and no intra-operative complications occurred. The pre-operative
      complains were relieved in all patients, and no recurrence was observed during 3
      18 month of follow-up. Six patients got dysphagia after operation; 5 of them were
      controlled through medication and psychological induction; 1 received esophageal
      dilatation by bougie. CONCLUSION: The application of biological mesh in
      laparoscopic anti-reflux procedure for gastroesophageal reflux disease is
      satisfactory.

PMID- 25851980
TI  - [Single-incision laparoscopic surgery with self-made port for totally
      extraperitoneal hernioplasty: a report of 7 cases].
AB  - OBJECTIVE: To explore the feasibility of single-incision laparoscopic totally
      extraperitoneal hernioplasty (SILS-TEP) with self-made port for repairing of
      inguinal hernia. METHODS: SILS-TEP was performed in 7 inguinal hernia patients (9
      sides) with conventional laparoscopic instruments and self-made port, which
      composed of a wound retractor, surgical gloves and 3 ordinary trocars. The
      clinical data and follow-up results of 7 cases were retrospectively collected and
      analyzed. RESULTS: The self-made port was applied for SILS-TEP uneventfully
      without the need of additional ports in all 7 patients (9 inguinal hernias). The
      median operating time was 90. 0 (70-125) min, intraoperative blood loss was 10. 0
      (5. 0-20. 0) mL and postoperative hospital stay was 2.0 (2. 0-4. 0) d. The median
      pain scores of visual analog scale (VAS) at 6 h,12 h, 24 h and 14 d were 3(2~4),
      2(1~2), 1(0~2) and 0(0~1), respectively. There were no intraoperative
      complications reported, and all patients were satisfied with wound healing. No
      hernia recurrence was observed during the 3-months of follow-up. CONCLUSION: Our
      initial experiences show that SILS-TEP with self-made port is a safe and feasible
      surgery, which can simplify the procedure with available equipments and reduce
      the cost, therefore can be applied in grass-root hospitals.

PMID- 25851981
TI  - [Correlation between follicle-stimulating hormone and total procollagen I N
      terminal propeptide in perimenopausal women].
AB  - OBJECTIVE: To investigate the correlation between serum levels of follicle
      stimulating hormone (FSH) and total procollagen I N-terminal propeptide (TP1NP)
      in perimenopausal women. METHODS: Total 274 women aged 33~60 y with
      perimenopausal period were enrolled in this study. Serum levels of FSH and TP1NP
      were detected by electrochemiluminescence. RESULTS: In 274 perimenopausal women,
      the average level of TP1NP was (48.99+/-20.31) ng/mL, which was positively
      correlated with FSH level (r=0.159, P=0.009). In 40-50 age group, TP1NP level in
      women with FSH<40 mIU/mL was lower than that in those with FSH>=40mIU/mL
      [(35.05+/-18.11) ng/mL vs (51.33+/-24.67) ng/mL; t=-2.954, P=0.004]. However, in
      <40 and 50-60 age groups, there were no significant differences in TP1NP levels
      between patients with FSH<40 mIU/mL and those with FSH>=40 mIU/mL (t=-0.063,
      P=0.950; t=1.177, P=0.242). Multiple linear regression analysis showed that
      standardized coefficients of age variable was 0.047 (P=0.448) and standardized
      coefficients of FSH variable was 0.146 (P=0.019). CONCLUSION: TP1NP levels showed
      a certain correlation with FSH in perimenopausal women, especially for women aged
      40-50, indicating that high FSH levels may be important factors for osteoporosis
      in postmenopausal women.

PMID- 25851982
TI  - [Effect of occlusal reconstruction on cerebral blood flow and cerebral oxygen
      saturation in patients with malocclusion].
AB  - OBJECTIVE: To investigate the effect of occlusal reconstruction on blood flow
      velocity and cerebral oxygen saturation in patients with malocclusion. METHODS:
      Thirty-three patients with malocclusion treated with occlusal reconstruction in
      Department of Stomatology, Medical School of Huzhou Normal College from Feb 2011
      to Oct 2013 were enrolled in the study. The systolic peak flow velocity (vs), end
      diastolic peak flow (vd) , mean peak flow velocity (vm) of middle cerebral artery
      and the oxygen saturation (rScO2) in the brain were detected at rest or chewing
      status by using transcranial Doppler color ultrasonography and near-infrared
      spectroscopy, respectively. RESULTS: In rest state, vm was significantly
      increased on 3 months after treatment, while vs and vd were significantly
      increased on 6 months after treatment and rScO2 were increased on 12 months after
      treatment (P<0.05). In chewing state, vs, vm, and rScO2 were increased on 3
      months after treatment, and vd was increased on 6 months after treatment
      (P<0.05). CONCLUSION: Occlusal reconstruction can increase blood flow velocity of
      middle cerebral artery and cerebral oxygen saturation and improve oxygen supply
      of the brain in patients with malocclusion.

PMID- 25851983
TI  - [Progress on matrix metalloproteinase in axonal regeneration].
AB  - Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases. MMPs can
      degrade and remodel extracellular matrix, also active or inactive many molecules
      attaching to matrix including receptors, growth factors and cytokines, so that
      injury-induced MMPs can change the extracellular environment to affect the axonal
      regeneration in central nervous system. In this review, with spinal cord injury
      (SCI) as an example we discuss the effects of MMPs on inflammation, neuronal
      viability, extracellular molecules, glial scar and axonal remyelination, which
      are all important to axonal regeneration.

PMID- 25851984
TI  - [Progress on association between low-density lipoprotein receptor and metabolic
      syndrome].
AB  - Low-density lipoprotein receptor (LDLR) and metabolic syndrome (MS) are closely
      correlated. Changes in LDLR expression, feedback regulation and degradation,
      impacts of LDLR deficiency on blood lipid levels, roles of LDLR in islet beta
      cell dysfunction and cholesterol homeostasis dysregulation, expression of LDLR
      gene nuclear transcription factors and polymorphism of LDLR gene segments are all
      involved in the development of specific components of MS. In recent years, a
      variety of targets and intervention mechanisms in relation to LDLR and MS have
      been extensively studied. Knowledge about association between LDLR and MS may
      contribute to the development of strategies for prevention and treatment of MS.
      This article reviews the update on the association between LDLR and MS.

PMID- 25851985
TI  - [Bioelectric-technology in tumor minimally invasive therapy--from the 11th
      International Bioelectrics Symposium].

PMID- 25851986
TI  - [Highlights of the 19th congress of Asia-Pacific Blood and Marrow
      Transplantation].

PMID- 25851987
TI  - Engineered microstructure granules for tailored drug release rate.
AB  - Biomaterials developed for controlled drug delivery have demonstrated excellent
      results in the present study. A biomaterial prepared using hydroxyapatite (HAp)
      was shown to have a hollow structure with the presence of interconnected pores to
      house drug carriers. The poly(lactic-co-glycolic acid) particles were used as
      drug carriers loaded with dexamethasone, a corticosteroid that is known to
      promote osteoinduction. The surface of the drug carriers was modified using
      polyethyleneimine, and then conjugated to the surface of HAp granules. The hollow
      HAp granules had drug carriers on both their inner and outer surfaces and showed
      a controlled drug release rate that was comparable to that of granules containing
      drug carriers on their outer surface alone. The pores were designed for insertion
      of drug carriers and preosteoblasts. Consequently, the biomaterials influenced
      cellular behavior by first promoting cell proliferation and then inducing early
      stage osteogenic differentiation. The effects of controlled release rate were
      evidenced for up to two weeks after cell seeding, resulting in an increase of
      osteogenic differentiation. In summary, drug carriers loaded onto hollow HAp
      granules were shown to be suitable for patients who require replacement of
      missing bone for repair of bone fractures that are extremely complex, pose a
      significant health risk to the patient, or fail to heal properly.

PMID- 25851990
TI  - Embolic stroke associated with intra-carotid injection of buprenorphine.

PMID- 25851993
TI  - Diagnosis of allergy against beta-lactams in primary care: prevalence and
      diagnostic criteria.
AB  - BACKGROUND: Secondary care studies showed that a recorded allergy to beta-lactams
      could not be confirmed by valid allergy testing in >85% of cases. In daily
      practice, recorded beta-lactam allergies probably cause prescription of secondary
      choice antibiotics. This overrating of beta-lactam allergy hampers appropriate
      use of narrow spectrum antibiotic and generates unnecessary cost and bacterial
      resistance. OBJECTIVE: To assess registration and over diagnosis of allergies
      against beta-lactams in Dutch primary care. METHODS: A retrospective cohort study
      in 8288 primary care subjects was performed. Patients with recorded allergy were
      identified through International Classification for Primary Care coding. Signs
      and symptoms of the recorded allergic reaction and patient's characteristics were
      extracted from patient's files and patients were sent a questionnaire. The
      probability of allergy was based on a composite reference standard that was
      scored by two authors independently. RESULTS: One hundred sixty-three subjects
      had a recorded allergy (2.0%). In 51.5% of cases, no characteristics of the
      recorded allergic reaction were reported in patients' medical files. Based on our
      composite reference standard, allergy was excluded in 19 subjects (11.7%). Risk
      factors for allergy registration were female gender, age <4 years, and the
      comorbidities-asthma, allergies and skin disorders. CONCLUSIONS: The prevalence
      of recorded allergy against beta-lactam antibiotics in a large Dutch primary care
      centre was 2%. Due to lack of registration of accompanying signs and symptoms of
      the recorded allergy, this diagnosis is uncertain in most patients. Better
      documentation and classification by a screening algorithm of future possible
      allergic reactions to beta-lactams are needed in primary care.

PMID- 25851992
TI  - Testing the waters: Ethical considerations for including PrEP in a phase IIb HIV
      vaccine efficacy trial.
AB  - BACKGROUND: The field of HIV prevention research has recently experienced some
      mixed results in efficacy trials of pre-exposure prophylaxis, vaginal
      microbicides, and HIV vaccines. While there have been positive trial results in
      some studies, in the near term, no single method will be sufficient to quell the
      epidemic. Improved HIV prevention methods, choices among methods, and coverage
      for all at-risk populations will be needed. The emergence of partially effective
      prevention methods that are not uniformly available raises complex ethical and
      scientific questions regarding the design of ongoing prevention trials. METHODS:
      We present here an ethical analysis regarding inclusion of pre-exposure
      prophylaxis in an ongoing phase IIb vaccine efficacy trial, HVTN 505. This is the
      first large vaccine efficacy trial to address the issue of pre-exposure
      prophylaxis, and the decisions made by the protocol team were informed by
      extensive stakeholder consultations. The key ethical concerns are analyzed here,
      and the process of stakeholder engagement and decision-making described.
      DISCUSSION: This discussion and analysis will be useful as current and future
      research teams grapple with ethical and scientific study design questions
      emerging with the rapidly expanding evidence base for HIV prevention.

PMID- 25851994
TI  - MiR-107 down-regulates SIAH1 expression in human breast cancer cells and
      silencing of miR-107 inhibits tumor growth in a nude mouse model of triple
      negative breast cancer.
AB  - We have reported that SIAH1 is down-regulated and associated with apoptosis and
      invasion in human breast cancer. However, the molecular mechanisms leading to
      SIAH1 down-regulation remain to be elucidated. Here, we demonstrated that miR-107
      directly down-regulates SIAH1 expression in human breast cancer cells. Over-
      expression of miR-107 reduced SIAH1 expression, promoted human breast cancer cell
      proliferation, colony formation, migration and invasion, and inhibited apoptosis.
      On the contrary, silencing of miR-107 increased SIAH1 expression and inhibited
      the tumor growth of MDA-MB-231 cells, a kind of triple-negative breast cancer
      (TNBC) cells, in vitro and in vivo. Our results reveal that miR-107 is an
      upstream regulator for SIAH1 down-regulation in human breast cancer cells and miR
      107 provides a potential effective target for the treatment of TNBC.

PMID- 25851995
TI  - Response to hydroxyurea among Kuwaiti patients with sickle cell disease and
      elevated baseline HbF levels.

PMID- 25851996
TI  - [Use of cold and cough medications prescribed in Primary Care clinics for
      children less than 14 years].
AB  - OBJECTIVE: To evaluate cold and cough medications and their suitability in
      children in Primary Health Care in Area V of the Asturian Health Service.
      MATERIAL AND METHODS: A cross-sectional, descriptive and retrospective study was
      conducted in which an analysis was performed of the respiratory diseases and the
      prescriptions of 6 Primary Health Care paediatricians who worked in Area V of the
      Asturian Health Service in 2011. An evaluation was made on the suitability of
      these medications. An analysis was also made of the drug datasheet and clinical
      recommendations (clinical guidelines, protocols or reports). RESULTS: A total of
      424 cold and cough drugs: 249 antitussives, 155 mucolytics, and 20 "others" were
      analyzed. The mean age was 5 years old. There was a total of 85.1% unsuitable
      prescriptions. Off-label drugs were used in 11.6%. The prescribing was considered
      unsuitable in 82.8% of prescriptions associated with R74, and 73% of R05. All of
      the prescription drugs in children under 6 years old were unsuitable.
      Mucolytics/"others" were not suitable in 99.4%, nor antitussives in 75.1%.
      CONCLUSIONS: There is a high level of cold and cough drugs being prescribed in
      children, with 85% of these being unsuitable. Children should only receive drugs
      with a good risk and benefit ratio. Pediatricians should try to improve the
      information about pediatric drug use and spread this information to parents,
      doctors and nurses.

PMID- 25851997
TI  - Solitary orange-yellow scalp lesion.

PMID- 25851999
TI  - Multifunctional MgO Layer in Perovskite Solar Cells.
AB  - A multifunctional magnesium oxide (MgO) layer was successfully introduced into
      perovskite solar cells (PSCs) to enhance their performance. MgO was coated onto
      the surface of mesoporous TiO(2) by the decomposition of magnesium acetate and,
      therefore, could block contact between the perovskite and TiO(2). X-ray
      photoelectron spectroscopy and infrared spectroscopy showed that the amount of
      H(2)O/hydroxyl absorbed on the TiO(2) decreased after MgO modification. The
      UV/Vis absorption spectra of the perovskite with MgO modification revealed an
      enhanced photoelectric performance compared with that of unmodified perovskite
      after UV illumination. In addition to the photocurrent, the photovoltage and fill
      factor also showed an enhancement after modification, which resulted in an
      increase in the overall efficiency of the cell from 9.6 to 13.9 %.
      Electrochemical impedance spectroscopy (EIS) confirmed that MgO acts as an
      insulating layer to reduce charge recombination.

PMID- 25851998
TI  - A germline MTOR mutation in Aboriginal Australian siblings with intellectual
      disability, dysmorphism, macrocephaly, and small thoraces.
AB  - We report on three Aboriginal Australian siblings with a unique phenotype which
      overlaps with known megalencephaly syndromes and RASopathies, including Costello
      syndrome. A gain-of-function mutation in MTOR was identified and represents the
      first reported human condition due to a germline, familial MTOR mutation. We
      describe the findings in this family to highlight that (i) the path to
      determination of pathogenicity was confounded by the lack of genomic reference
      data for Australian Aboriginals and that (ii) the disease biology, functional
      analyses in this family, and studies on the tuberous sclerosis complex support
      consideration of an mTOR inhibitor as a therapeutic agent.

PMID- 25852000
TI  - A Synthetic Route to Chiral Dihydrobenzothiazines through Ring Opening of
      Activated Aziridines with 2-Halothiophenols/Copper-Powder-Mediated C-N
      Cyclization.
AB  - A simple protocol for the synthesis of dihydrobenzothiazines through regio- and
      stereoselective S(N)2-type ring opening of N-tosylaziridines with sulfur
      nucleophiles followed by copper-powder-mediated intramolecular C-N cyclization in
      excellent yields (up to 95%) with high diastereo- and enantioselectivity (up to
      >99%) is reported.

PMID- 25852001
TI  - Mitochondrial oxidative stress mediates high-phosphate-induced secretory defects
      and apoptosis in insulin-secreting cells.
AB  - Inorganic phosphate (Pi) plays an important role in cell signaling and energy
      metabolism. In insulin-releasing cells, Pi transport into mitochondria is
      essential for the generation of ATP, a signaling factor in metabolism-secretion
      coupling. Elevated Pi concentrations, however, can have toxic effects in various
      cell types. The underlying molecular mechanisms are poorly understood. Here, we
      have investigated the effect of Pi on secretory function and apoptosis in INS-1E
      clonal beta-cells and rat pancreatic islets. Elevated extracellular Pi (1~5 mM)
      increased the mitochondrial membrane potential (DeltaPsim), superoxide
      generation, caspase activation, and cell death. Depolarization of the DeltaPsim
      abolished Pi-induced superoxide generation. Butylmalonate, a nonselective blocker
      of mitochondrial phosphate transporters, prevented DeltaPsim hyperpolarization,
      superoxide generation, and cytotoxicity caused by Pi. High Pi also promoted the
      opening of the mitochondrial permeability transition (PT) pore, leading to
      apoptosis, which was also prevented by butylmalonate. The mitochondrial
      antioxidants mitoTEMPO or MnTBAP prevented Pi-triggered PT pore opening and
      cytotoxicity. Elevated extracellular Pi diminished ATP synthesis, cytosolic
      Ca(2+) oscillations, and insulin content and secretion in INS-1E cells as well as
      in dispersed islet cells. These parameters were restored following preincubation
      with mitochondrial antioxidants. This treatment also prevented high-Pi-induced
      phosphorylation of ER stress proteins. We propose that elevated extracellular Pi
      causes mitochondrial oxidative stress linked to mitochondrial hyperpolarization.
      Such stress results in reduced insulin content and defective insulin secretion
      and cytotoxicity. Our data explain the decreased insulin content and secretion
      observed under hyperphosphatemic states.

PMID- 25852002
TI  - Lipid-induced insulin resistance does not impair insulin access to skeletal
      muscle.
AB  - Elevated plasma free fatty acids (FFA) induce insulin resistance in skeletal
      muscle. Previously, we have shown that experimental insulin resistance induced by
      lipid infusion prevents the dispersion of insulin through the muscle, and we
      hypothesized that this would lead to an impairment of insulin moving from the
      plasma to the muscle interstitium. Thus, we infused lipid into our anesthetized
      canine model and measured the appearance of insulin in the lymph as a means to
      sample muscle interstitium under hyperinsulinemic euglycemic clamp conditions.
      Although lipid infusion lowered the glucose infusion rate and induced both
      peripheral and hepatic insulin resistance, we were unable to detect an impairment
      of insulin access to the lymph. Interestingly, despite a significant, 10-fold
      increase in plasma FFA, we detected little to no increase in free fatty acids or
      triglycerides in the lymph after lipid infusion. Thus, we conclude that
      experimental insulin resistance induced by lipid infusion does not reduce insulin
      access to skeletal muscle under clamp conditions. This would suggest that the
      peripheral insulin resistance is likely due to reduced cellular sensitivity to
      insulin in this model, and yet we did not detect a change in the tissue
      microenvironment that could contribute to cellular insulin resistance. 

PMID- 25852004
TI  - Positive long-term outcomes from presuckling calcium supplementation in lactating
      rats and the offspring.
AB  - Adequate dietary calcium intake and the enhanced intestinal calcium absorption in
      lactating mothers have long been postulated to prevent maternal bone loss and
      benefit neonatal bone growth. We recently showed that calcium supplementation
      just before breastfeeding efficiently alleviated lactation-induced bone loss in
      dams as well as increased milk calcium concentration, which led to higher bone
      mineral density (BMD) in the newborns. Herein, we further elaborated in detail
      how presuckling calcium supplements worked in lactating rats and how they
      benefited bone growth in the offspring. As revealed by bone histomorphometry,
      presuckling supplement with calcium alone reduced the osteoclast surface and
      active erosion surface, leading to an increase in trabecular thickness without
      changes in trabecular separation or number in dams. The beneficial effects of
      presuckling calcium supplements, particularly the regimen containing glucose and
      galactose that enhanced intestinal calcium absorption, were found to last for 3
      mo postweaning, although it could not restore estrogen-deficient osteopenia
      induced by ovariectomy. Regarding the neonatal benefits, pups nursed by calcium
      supplemented dams exhibited increases in trabecular BMD, which could be observed
      even at the age of 27 wk. Bone elongation was also greater in pups of calcium
      supplemented dams, which was due possibly to accelerated growth plate chondrocyte
      turnover. It could be concluded that calcium supplements markedly diminished the
      lactation-induced osteopenia in dams and positively affected BMD and bone
      elongation in growing rats. Therefore, presuckling calcium supplementation in
      lactating mothers is an effective strategy for promoting a long-lasting high bone
      density for both mother and the offspring. 

PMID- 25852003
TI  - Systemic alterations in the metabolome of diabetic NOD mice delineate increased
      oxidative stress accompanied by reduced inflammation and hypertriglyceremia.
AB  - Nonobese diabetic (NOD) mice are a commonly used model of type 1 diabetes (T1D).
      However, not all animals will develop overt diabetes despite undergoing similar
      autoimmune insult. In this study, a comprehensive metabolomic approach,
      consisting of gas chromatography time-of-flight (GC-TOF) mass spectrometry (MS),
      ultra-high-performance liquid chromatography-accurate mass quadruple time-of
      flight (UHPLC-qTOF) MS and targeted UHPLC-tandem mass spectrometry-based
      methodologies, was used to capture metabolic alterations in the metabolome and
      lipidome of plasma from NOD mice progressing or not progressing to T1D. Using
      this multi-platform approach, we identified >1,000 circulating lipids and
      metabolites in male and female progressor and nonprogressor animals (n = 71).
      Statistical and multivariate analyses were used to identify age- and sex
      independent metabolic markers, which best differentiated metabolic profiles of
      progressors and nonprogressors. Key T1D-associated perturbations were related
      with 1) increases in oxidation products glucono-delta-lactone and galactonic acid
      and reductions in cysteine, methionine and threonic acid, suggesting increased
      oxidative stress; 2) reductions in circulating polyunsaturated fatty acids and
      lipid signaling mediators, most notably arachidonic acid (AA) and AA-derived
      eicosanoids, implying impaired states of systemic inflammation; 3) elevations in
      circulating triacylglyercides reflective of hypertriglyceridemia; and 4)
      reductions in major structural lipids, most notably lysophosphatidylcholines and
      phosphatidylcholines. Taken together, our results highlight the systemic
      perturbations that accompany a loss of glycemic control and development of overt
      T1D. 

PMID- 25852005
TI  - An index of parameter reproducibility accounting for estimation uncertainty:
      theory and case study on beta-cell responsivity and insulin sensitivity.
AB  - Parameter reproducibility is necessary to perform longitudinal studies where
      parameters are assessed to monitor disease progression or effect of therapy but
      are also useful in powering the study, i.e., to define how many subjects should
      be studied to observe a given effect. The assessment of parameter reproducibility
      is usually accomplished by methods that do not take into account the fact that
      these parameters are estimated with uncertainty. This is particularly relevant in
      physiological and clinical studies where usually reproducibility cannot be
      assessed by multiple testing and is usually assessed from a single replication of
      the test. Working in a suitable stochastic framework, here we propose a new index
      (S) to measure reproducibility that takes into account parameter uncertainty and
      is particularly suited to handle the normal testing conditions of physiological
      and clinical investigations. Simulation results prove that S, by properly taking
      into account parameter uncertainty, is more accurate and robust than the methods
      available in the literature. The new metric is applied to assess reproducibility
      of insulin sensitivity and beta-cell responsivity of a mixed-meal tolerance test
      from data obtained in the same subjects retested 1 wk apart. Results show that
      the indices of insulin sensitivity and beta-cell responsivity to glucose are well
      reproducible. We conclude that the oral minimal models provide useful indices
      that can be used safely in prospective studies or to assess the efficacy of a
      given therapy. 

PMID- 25852006
TI  - Estradiol-mediated hepatocyte growth factor is involved in the implantation of
      endometriotic cells via the mesothelial-to-mesenchymal transition in the
      peritoneum.
AB  - The pathogenesis of endometriosis, a chronic painful gynecological disease
      characterized by the presence of endometrial tissue located outside of the uterus
      and often adhering to the peritoneum, is known to be estrogen dependent. However,
      the precise pathophysiology of endometriosis remains elusive. Recent studies
      indicate that the epithelial-to-mesenchymal transition (EMT) of human endometrial
      cells is important for the progression of endometriosis, and another previous
      study has implicated hepatocyte growth factor (HGF) in endometriosis progression.
      The aim of the present study was to examine the role of estradiol in the
      regulation of HGF production and progression of peritoneal endometriosis,
      focusing on the interactions between the peritoneum and endometriotic cells.
      Consequently, estradiol was found to promote the proliferation, invasion, and
      migration of immortalized human endometrial epithelial cells (hEECs) via HGF
      upregulation, and the estradiol-induced direct binding of estrogen receptor-alpha
      to the HGF promoter was confirmed on a chromatin immunoprecipitation (ChIP)
      assay. Estradiol also induced the EMT in hEECs by promoting HGF production.
      Furthermore, human mesothelial cells underwent the mesothelial-to-mesenchymal
      transition (MMT) during culture with estradiol-stimulated hEEC conditioned
      medium. Importantly, estradiol itself did not induce the MMT, and the estradiol
      stimulated hEEC-conditioned medium in the presence of HGF antibodies reversed the
      MMT process. These results, which were obtained using immortalized hEECs,
      indicate that estradiol-induced HGF production may play a crucial role in the
      peritoneal implantation of human endometriotic cells by exerting proliferative
      and invasive effects via the EMT in hEECs and promoting the MMT in mesothelial
      cells. 

PMID- 25852007
TI  - ATGL-mediated triglyceride turnover and the regulation of mitochondrial capacity
      in skeletal muscle.
AB  - Emerging evidence indicates that skeletal muscle lipid droplets are an important
      control point for intracellular lipid homeostasis and that regulating fatty acid
      fluxes from lipid droplets might influence mitochondrial capacity. We used
      pharmacological blockers of the major triglyceride lipases, adipose triglyceride
      lipase (ATGL) and hormone-sensitive lipase, to show that a large proportion of
      the fatty acids that are transported into myotubes are trafficked through the
      intramyocellular triglyceride pool. We next tested whether increasing lipolysis
      from intramyocellular lipid droplets could activate transcriptional responses to
      enhance mitochondrial and fatty acid oxidative capacity. ATGL was overexpressed
      by adenoviral and adenoassociated viral infection in C2C12 myotubes and the
      tibialis anterior muscle of C57Bl/6 mice, respectively. ATGL overexpression in
      C2C12 myotubes increased lipolysis, which was associated with increased
      peroxisome proliferator-activated receptor (PPAR)-? activity, transcriptional
      upregulation of some PPAR? target genes, and enhanced mitochondrial capacity. The
      transcriptional responses were specific to ATGL actions and not a generalized
      increase in fatty acid flux in the myotubes. Marked ATGL overexpression (20-fold)
      induced modest molecular changes in the skeletal muscle of mice, but these
      effects were not sufficient to alter fatty acid oxidation. Together, these data
      demonstrate the importance of lipid droplets for myocellular fatty acid
      trafficking and the capacity to modulate mitochondrial capacity by enhancing
      lipid droplet lipolysis in vitro; however, this adaptive program is of minor
      importance when superimposing the normal metabolic stresses encountered in free
      moving animals. 

PMID- 25852009
TI  - Prognostic significance of autocrine motility factor receptor expression by
      colorectal cancer and lymph node metastases.
AB  - BACKGROUND: Autocrine motility factor receptor (AMFR) has been linked to
      metastasis and tumorigenicity. The aim of this study was to evaluate expression
      and prognostic significance of AMFR in colorectal carcinoma. METHODS: AMFR
      expression was evaluated in 127 colon cancer specimens, 131 rectal cancer
      specimens, and 47 colonic and 25 rectal corresponding lymph node metastases.
      Clinicopathological correlates of prognostic significance were established by
      univariate and multivariate analysis. Spearman's correlation determined the
      association of expression between cancers and their metastases. RESULTS: AMFR was
      over-expressed by 22% of colon cancers and 18% of rectal cancers. AMFR over
      expression correlated significantly with improved disease-free survival (DFS) (P
      < .05) in colon cancer and decreased DFS in corresponding nodal metastases. In
      rectal cancer, AMFR over-expression significantly correlated with decreased
      overall survival, DFS, and disease-specific survival (P < .001, P = .031, P =
      .005, respectively) and decreased overall survival in corresponding metastases.
      CONCLUSION: AMFR may serve as a molecular prognosticator for colon cancer and
      rectal cancer.

PMID- 25852008
TI  - Long-chain acylcarnitines activate cell stress and myokine release in C2C12
      myotubes: calcium-dependent and -independent effects.
AB  - Acylcarnitines, important lipid biomarkers reflective of acyl-CoA status, are
      metabolites that possess bioactive and inflammatory properties. This study
      examined the potential for long-chain acylcarnitines to activate cellular
      inflammatory, stress, and death pathways in a skeletal muscle model.
      Differentiated C2C12 myotubes treated with l-C14, C16, C18, and C18:1 carnitine
      displayed dose-dependent increases in IL-6 production with a concomitant rise in
      markers of cell permeability and death, which was not observed for shorter chain
      lengths. l-C16 carnitine, used as a representative long-chain acylcarnitine at
      initial extracellular concentrations >=25 MUM, increased IL-6 production 4.1-,
      14.9-, and 31.4-fold over vehicle at 25, 50, and 100 MUM. Additionally, l-C16
      carnitine activated c-Jun NH2-terminal kinase, extracellular signal-regulated
      kinase, and p38 mitogen-activated protein kinase between 2.5- and 11-fold and
      induced cell injury and death within 6 h with modest activation of the apoptotic
      caspase-3 protein. l-C16 carnitine rapidly increased intracellular calcium, most
      clearly by 10 MUM, implicating calcium as a potential mechanism for some
      activities of long-chain acylcarnitines. The intracellular calcium chelator BAPTA
      AM blunted l-C16 carnitine-mediated IL-6 production by >65%. However, BAPTA-AM
      did not attenuate cell permeability and death responses, indicating that these
      outcomes are calcium independent. The 16-carbon zwitterionic compound
      amidosulfobetaine-16 qualitatively mimicked the l-C16 carnitine-associated cell
      stress outcomes, suggesting that the effects of high experimental concentrations
      of long-chain acylcarnitines are through membrane disruption. Herein, a model is
      proposed in which acylcarnitine cell membrane interactions take place along a
      spectrum of cellular concentrations encountered in physiological-to
      pathophysiological conditions, thus regulating function of membrane-based systems
      and impacting cell biology. 

PMID- 25852010
TI  - Prognostic value of volume-based measurements on (11)C-methionine PET in glioma
      patients.
AB  - PURPOSE: (11)C-methionine (MET) PET is an established diagnostic tool for glioma.
      Studies have suggested that MET uptake intensity in the tumor is a useful index
      for predicting patient outcome. Because MET uptake is known to reflect tumor
      expansion more accurately than MRI, we aimed to elucidate the association between
      volume-based tumor measurements and patient prognosis. METHODS: The study
      population comprised 52 patients with newly diagnosed glioma who underwent PET
      scanning 20 min after injection of 370 MBq MET. The tumor was contoured using a
      threshold of 1.3 times the activity of the contralateral normal cortex. Metabolic
      tumor volume (MTV) was defined as the total volume within the boundary. Total
      lesion methionine uptake (TLMU) was defined as MTV times the mean standardized
      uptake value (SUVmean) within the boundary. The tumor-to-normal ratio (TNR),
      calculated as the maximum standardized uptake value (SUVmax) divided by the
      contralateral reference value, was also recorded. All patients underwent surgery
      (biopsy or tumor resection) targeting the tissue with high MET uptake. The Kaplan
      Meier method was used to estimate the predictive value of each measurement.
      RESULTS: Grade II tumor was diagnosed in 12 patients (3 diffuse astrocytoma, 2
      oligodendroglioma, and 7 oligoastrocytoma), grade III in 18 patients (8
      anaplastic astrocytoma, 6 anaplastic oligodendroglioma, and 4 anaplastic
      oligoastrocytoma), and grade IV in 22 patients (all glioblastoma). TNR, MTV and
      TLMU were 3.1 +/- 1.2, 51.6 +/- 49.9 ml and 147.7 +/- 153.3 ml, respectively.
      None of the three measurements was able to categorize the glioma patients in
      terms of survival when all patients were analyzed. However, when only patients
      with astrocytic tumor (N = 33) were analyzed (i.e., when those with
      oligodendroglial components were excluded), MTV and TLMU successfully predicted
      patient outcome with higher values associated with a poorer prognosis (P < 0.05
      and P < 0.01, respectively), while the predictive ability of TNR did not reach
      statistical significance (P = NS). CONCLUSION: MTV and TLMU may be useful for
      predicting outcome in patients with astrocytic tumor.

PMID- 25852012
TI  - European and international links.

PMID- 25852011
TI  - Thoracic staging of non-small-cell lung cancer using integrated (18)F-FDG PET/MR
      imaging: diagnostic value of different MR sequences.
AB  - PURPOSE: To compare the accuracy of different MR sequences in simultaneous PET/MR
      imaging for T staging in non-small-cell lung cancer in relation to
      histopathology. METHODS: The study included 28 patients who underwent dedicated
      thoracic PET/MR imaging before tumour resection. Local tumour staging was
      performed separately by three readers with each of the following MR sequences
      together with PET: transverse T2 BLADE, transverse non-enhanced and contrast
      enhanced T1 FLASH, T1 3D Dixon VIBE in transverse and coronal orientation,
      coronal T2 HASTE, and coronal TrueFISP. The staging results were compared with
      histopathology after resection as the reference standard. Differences in the
      accuracy of T staging among the MR sequences were evaluated using McNemar's test.
      Due to multiple testing, Bonferroni correction was applied to prevent
      accumulation of alpha errors; p < 0.0024 was considered statistically
      significant. RESULTS: Compared with histopathology, T-staging accuracy was 69%
      with T2 BLADE, 68% with T2 HASTE, 59% with contrast-enhanced T1 FLASH, 57% with
      TrueFISP, 50 % with non-enhanced T1 FLASH, and 45% and 48% with T1 3D Dixon VIBE
      in transverse and coronal orientation, respectively. Staging accuracy with T2
      BLADE was significantly higher than with non-enhanced T1 FLASH and with T1 3D
      Dixon VIBE in transverse and coronal orientations (p < 0.0024). T2 HASTE had a
      significantly higher T-staging accuracy than transverse T1 3D-Dixon-VIBE (p <
      0.0024). CONCLUSION: Transverse T2 BLADE images provide the highest accuracy for
      local tumour staging and should therefore be included in dedicated thoracic
      PET/MR protocols. As T1 3D Dixon VIBE images acquired for attenuation correction
      performed significantly worse, this sequence cannot be considered sufficiently
      accurate for local tumour staging in the thorax.

PMID- 25852013
TI  - Commentary on Singh et al. Nonunion after trapeziometacarpal arthrodesis:
      comparison between K-wire and internal fixation and Smeraglia et al.
      Trapeziometacarpal arthrodesis: is bone union necessary for a good outcome?

PMID- 25852014
TI  - Re: Renfree KJ. Percutaneous in situ versus open arthrodesis of the distal
      interphalangeal joint. J Hand Surg Eur. Epub ahead of print 18 March 2014. DOI:
      10.1177/1753193414527387.

PMID- 25852015
TI  - Re: Tonkin, M. A. On the classification of congenital thumb hypoplasia. J Hand
      Surg Eur. 2014, 39: 948-55.

PMID- 25852016
TI  - Re: Wong J. and McGrouther D. A. Minimizing trauma over 'no man's land' for
      flexor tendon retrieval. J Hand Surg Eur. 2014, 39: 1004-6.

PMID- 25852017
TI  - The lost art of single-stage flexor tendon grafting.

PMID- 25852021
TI  - Keratinising cystitis with intestinal metaplasia following a Crohn's vesico
      intestinal fistula.

PMID- 25852020
TI  - Hormone Use, Reproductive History, and Risk of Lung Cancer: The Women's Health
      Initiative Studies.
AB  - INTRODUCTION: Results from the Women's Health Initiative clinical trials
      demonstrated no increase in the risk of lung cancer in postmenopausal women
      treated with hormone therapy (HT). We conducted a joint analysis of the Women's
      Health Initiative observational study data and clinical trials data to further
      explore the association between estrogen and estrogen-related reproductive
      factors and lung cancer risk. METHODS: Reproductive history, oral contraceptive
      use, and postmenopausal HT were evaluated in 160,855 women with known HT
      exposures. Follow-up for lung cancer was through September 17, 2012; 2467
      incident lung cancer cases were ascertained, with median follow-up of 14 years.
      RESULTS: For all lung cancers, women with previous use of estrogen plus progestin
      of less than 5 years (hazard ratio = 0.84; 95% confidence interval = 0.71-0.99)
      were at reduced risk. A limited number of reproductive factors demonstrated
      associations with risk. There was a trend toward decreased risk with increasing
      age at menopause (ptrend = 0.04) and a trend toward increased risk with
      increasing number of live births (ptrend = 0.03). Reduced risk of non-small-cell
      lung cancer was associated with age 20-29 years at first live birth. Risk
      estimates varied with smoking history, years of HT use and previous bilateral
      oophorectomy. CONCLUSIONS: Indirect measures of estrogen exposure to lung tissue,
      as used in this study, provide only weak evidence for an association between
      reproductive history or HT use and risk of lung cancer. More detailed mechanistic
      studies and evaluation of risk factors in conjunction with estrogen receptor
      expression in the lung should continue as a role for estrogen cannot be ruled out
      and may hold potential for prevention and treatment strategies.

PMID- 25852022
TI  - Advantages of single-puncture transperineal saturation biopsy of prostate:
      analysis of outcomes in 125 patients using our scheme.
AB  - PURPOSE: Stereotactic biopsy has improved prostate cancer detection. Although the
      new approach is superior, standard procedure is still useful in a cohort of
      patients in whom MRI is not available. The standard saturation biopsy technique
      is still debatable. We describe our technique and analyze its outcomes. MATERIALS
      AND METHODS: One hundred twenty-five patients underwent saturation biopsy through
      a single transperineal access. Mean age was 64.73 year, mean PSA was 9.49 ng/ml,
      mean PSA density was 0.184, and mean prostate volume was 57.95 g. All patients
      underwent at least one previous prostatic biopsy: 24.8% of cases had diagnosis of
      atypical small acinar proliferation, 39.2% of cases had multifocal high-grade
      prostatic intraepithelial neoplasia, and 36% of cases had inflammation or benign
      prostatic hyperplasia. RESULTS: The detection rate was 38.4%. Prostate cancer
      occurred in 61.3% of patients with previous ASAP (p < 0.007). Cancer detection
      rate decreased with increasing number of previous biopsy and with increasing
      prostate volume (p < 0.001) and increased with increasing PSA density (p = 0.03).
      No major complications were reported. CONCLUSION: The traditional saturation
      biopsy may be useful when targeted biopsy cannot be used. Our technique is
      accurate for cancer detection. It can offer some advantages in comparison with
      other approaches.

PMID- 25852023
TI  - Aeromonas aquatica sp. nov., Aeromonas finlandiensis sp. nov. and Aeromonas lacus
      sp. nov. isolated from Finnish waters associated with cyanobacterial blooms.
AB  - Three groups of Aeromonas strains isolated from Finland lakes experiencing
      cyanobacterial blooms could not be assigned to any known species of this genus on
      the basis of 16S rRNA and rpoD gene sequences. The Multilocus Phylogenetic
      Analysis (MLPA) of the concatenated sequence of seven genes (gyrB, rpoD, recA,
      dnaJ, gyrA, dnaX and atpD; 4093bp) showed that the three groups of strains did
      not cluster with any known Aeromonas spp. and formed three independent lineages.
      This was confirmed by performing the analysis with their closest relatives using
      15 genes (the latter 7 and cpn60, dnaK, gltA, mdh, radA, rpoB, tsf, zipA;
      8751bp). Furthermore, ANI results between the genomes of the type strains of the
      three potential new species and those of their close relatives were all <96%
      which is the previously proposed cutoff value for differentiating species within
      this genus. The in silico DDH values of the three type strains of the new species
      also showed a similarity<70% with the most closely related species indicating
      they belong to different taxa. The three groups of strains could be
      differentiated from each other and from other known Aeromonas species on the
      basis of several phenotypic characters. This polyphasic study revealed that the 3
      groups of strains represent 3 novel Aeromonas species for which the names
      Aeromonas aquatica sp. nov. (type strain AE235T=CECT 8025T=LMG 26712T), Aeromonas
      finlandiensis sp. nov. (type strain 4287DT=CECT 8028T=LMG 26709T) and Aeromonas
      lacus sp. nov. (type strain AE122T=CECT 8024T=LMG 26710T) are proposed.

PMID- 25852024
TI  - Validity of GT3X and Actiheart to estimate sedentary time and breaks using
      ActivPAL as the reference in free-living conditions.
AB  - Sedentary time, specifically sitting/reclining, is a risk factor for many non
      communicable diseases and premature mortality. Inclinometers have been used as a
      valid measurement of sedentary time and its patterns; however, there is a lack of
      information regarding the validity of alternative accelerometry and heart rate
      methods. The validity of GT3X and Actiheart in estimating changes in daily
      sedentary time and breaks, during free-living settings, using ActivPAL as the
      reference was examined. A crossover randomized control trial of an intervention
      that aimed to reduce ~3 h/day of sitting time included 10 overweight/obese adults
      (37-65 years). Participants had a total of 74 valid days for the three devices
      (29 controls; 45 interventions). For ActivPAL, sedentary time was measured
      directly based upon posture (sitting/reclining); Actiheart, the presumed MET
      cutpoint for sedentary time (<1.5 METs) based on accelerometry+heart rate; GT3X,
      the traditional <100countsmin(-1). A break in sedentary time was defined as when
      the participants were above the aforementioned cutoffs. GT3X overestimated and
      Actiheart underestimated sedentary time (bias=135min; bias=-156min, respectively)
      and both methods overestimated breaks in sedentary time (bias=78; bias=235
      breaks, respectively). The GT3X method was in better agreement with the ActivPAL
      sedentary time (r2=0.70; concordance correlation coefficient (CCC)=0.56) than the
      Actiheart (r2=0.24; CCC=0.31). The present results highlight the magnitude of
      potential errors in estimating sedentary time and breaks from common alternative
      methods other than ActivPAL. Because misclassification errors from the commonly
      used surrogates are potentially large, this raises concern that alternative
      methods used in many epidemiological observations may have underestimated the
      true effects caused by too much sitting (ClinicalTrials.govID:NCT02007681).

PMID- 25852025
TI  - Plasma glucose kinetics and response of insulin and GIP following a cereal
      breakfast in female subjects: effect of starch digestibility.
AB  - BACKGROUND/OBJECTIVES: Foods with high contents of slowly digestible starch (SDS)
      elicit lower glycemic responses than foods with low contents of SDS but there has
      been debate on the underlying changes in plasma glucose kinetics, that is,
      respective contributions of the increase in the rates of appearance and
      disappearance of plasma glucose (RaT and RdT), and of the increase in the rate of
      appearance of exogenous glucose (RaE) and decrease in endogenous glucose
      production (EGP). SUBJECTS/METHODS: Sixteen young healthy females ingested in
      random order four types of breakfasts: an extruded cereal (0.3% SDS: Lo-SDS
      breakfast) or one of three biscuits (39-45% SDS: Hi-SDS breakfasts). The flour in
      the cereal products was labeled with (13)C, and plasma glucose kinetics were
      measured using [6,6-(2)H2]glucose infusion, along with the response of plasma
      glucose, insulin and glucose-dependent insulinotropic peptide (GIP)
      concentrations. RESULTS: When compared with the Lo-SDS breakfast, after the three
      Hi-SDS breakfasts, excursions in plasma glucose, the response of RaE, RaT and
      RdT, and the reduction in EGP were significantly lower (P<0.05). The amount of
      exogenous glucose absorbed over the 4.5-h postprandial period was also
      significantly lower by ~31% (P<0.001). These differences were associated with
      lower responses of GIP and insulin concentrations. CONCLUSIONS: Substituting
      extruded cereals with biscuits slows down the availability of glucose from the
      breakfast and its appearance in peripheral circulation, blunts the changes in
      plasma glucose kinetics and homeostasis, reduces excursions in plasma glucose,
      and possibly distributes the glucose ingested over a longer period following the
      meal.

PMID- 25852027
TI  - Prenatal exposure to vitamin-D from fortified margarine and milk and body size at
      age 7 years.
AB  - BACKGROUND/OBJECTIVES: Prenatal vitamin-D deficiency may be associated with
      increased risk of obesity later in life. Using two national vitamin-D
      fortification programs as the setting for a societal experiment, we investigated
      whether exposure to vitamin-D from fortified margarine and low-fat milk during
      foetal life was associated with body size at 7 years of age. SUBJECTS/METHODS:
      Vitamin-D fortification of margarine was mandatory in Denmark from 1961 to 1985,
      and voluntary fortification of low-fat milk was permitted from 1972 to 1976.
      Using information on body mass index (BMI) Z-score at the age of 7 years of
      54,270 children, who were measured during the mandatory Copenhagen School Health
      examination, we compared children according to whether the mothers were pregnant
      during the fortification programs or not. The comparisons were performed for
      children born just before and after initiation or termination of margarine and
      milk fortification periods, respectively. In total four sets of analyses were
      performed. RESULTS: We observed no difference in mean BMI Z-score between
      children exposed to vitamin-D fortification in utero and non-exposed children.
      Similar results were observed for overweight and obesity. CONCLUSIONS: Prenatal
      exposure to vitamin-D from fortification of margarine and low-fat milk showed no
      association with body size at 7 years.

PMID- 25852026
TI  - Colors of fruits and vegetables and 3-year changes of cardiometabolic risk
      factors in adults: Tehran lipid and glucose study.
AB  - BACKGROUND/OBJECTIVES: We aimed to investigate the associations of colors of
      fruit and vegetable (FV) subgroups, with 3-year changes of cardiometabolic risk
      factors. SUBJECTS/METHODS: This longitudinal study was conducted in the framework
      of Tehran Lipid and Glucose Study, between 2006-2008 and 2009-2011, on 1272
      adults. Total intake of FV and their subgroups have been assessed by a validated
      semi-quantitative food frequency questionnaire at baseline (2006-2008) and again
      at the second examination (2009-2011). Demographics, anthropometrics and
      biochemical measures were evaluated at baseline and 3 years later. The
      associations of anthropometric and lipid profile changes with FV subgroups were
      estimated. RESULTS: The mean age of men and women at baseline was 39.8+/-12.7 and
      37.3+/-12.1 years, respectively. Mean total intake of FV, red/purple, yellow,
      green, orange and white FV was 706+/-337, 185+/-95, 141+/-91, 152+/-77, 141+/-87
      and 22+/-18 g/day, respectively. In men, 3-year changes of weight (beta=-0.13,
      P=0.01) and waist circumference (beta=-0.14, P=0.01) were related to intake of
      red/purple FV; the yellow group was inversely associated with 3-year changes of
      total cholesterol (beta=-0.09, P=0.03) and High-density lipoprotein cholesterol
      (beta=-0.11, P=0.03). Consumption of green and white FV was inversely related to
      abdominal fat gain, and atherogenic lipid parameters in men (P<0.05). In women,
      higher intake of red/purple FV was associated to lower weight and abdominal fat
      gain, fasting serum glucose and total cholesterol (P<0.05); yellow FV was also
      related to 3-year weight gain (beta=-0.11, P=0.01). CONCLUSIONS: Various colors
      of FV subgroups had different effects on cardiometabolic risk factors; higher
      intake of red/purple FV may be related to lower weight and abdominal fat gain,
      and yellow, green and white FV may be related to lipid parameters.

PMID- 25852028
TI  - Preliminary validation and principal components analysis of the Control of Eating
      Questionnaire (CoEQ) for the experience of food craving.
AB  - BACKGROUND/OBJECTIVES: The Control of Eating Questionnaire (CoEQ) comprises 21
      items that are designed to assess the severity and type of food cravings an
      individual experiences over the previous 7 days. The CoEQ has been used in
      clinical trials as a multi-dimensional measure of appetite, craving and mood
      regulation however its underlying component structure has yet to be determined.
      The current paper has two aims; (1) to examine the psychometric properties, and
      internal consistency of the CoEQ; and (2) to provide a preliminary examination of
      the underlying components by exploring their construct and predictive validity.
      SUBJECTS/METHODS: Data were pooled from four studies in which a total 215 adults
      (80% women; Age=29.7 +/- 10.3; BMI=26.5 +/- 5.2) had completed the CoEQ alongside
      measures of psychometric eating behaviour traits, ad libitum food intake, and
      body composition. A principal components analysis (PCA) and parallel analysis was
      conducted to examine the underlying structure of the questionnaire. The resulting
      subscales were tested for internal consistency (Cronbach's alpha=0.66-0.88).
      RESULTS: PCA revealed four components that explained 54.5% of the variance. The
      components were identified as: Craving Control, Positive Mood, Craving for Sweet,
      and Craving for Savoury. Associations between the underlying CoEQ subscales and
      measures of body composition and eating behaviour traits confirmed construct
      validity of the subscales. The associations between the subscales and snack food
      selection and intake of palatable snack foods supported the CoEQ's predictive
      validity. CONCLUSIONS: The CoEQ has good psychometric properties with a clear
      component structure and acceptable internal consistency. This preliminary
      validation supports the CoEQ as a measure of the experience of food cravings.

PMID- 25852029
TI  - Hexasomy 13q31.3q34 due to two marker chromosomes with inverted duplication in a
      fetus with increased nuchal translucency.
AB  - BACKGROUND: Small supernumerary marker chromosomes are structurally rearranged
      chromosomes that can be formed from different chromosomal fragments and cannot be
      identified using chromosomal banding analysis. Their examination has to be
      complemented by additional analyses like fluorescent in situ hybridization or
      array comparative genomic hybridization. METHODS: We report on partial hexasomy
      of chromosome 13q in a fetus of a pregnant woman referred to genetic counseling
      because of increased fetal nuchal translucency and increased risk of trisomy 21
      and trisomy 18 in first-trimester combined prenatal screening. Using chromosome
      banding analysis, in situ hybridization and array comparative hybridization we
      revealed the presence of two marker chromosomes with inverted duplication
      resulting in hexasomy of a 22.6 Mbp fragment in chromosomal region 13q31.3-13q34
      with the lack of chromosome 13 centromere. RESULTS: The fetus presented
      dysmorphic facial features, head and body disproportion, wide neck, ambiguous
      genitalia, incorrect position of the anus, and symmetrical shortening of the long
      bones were present in our described case. Some of these features were in
      accordance with other published cases. Other most often described features in
      tetrasomy were: microphtalmia or other major eye defects, ear abnormalities and
      deafness, hemangiomata, hypotelorism, severe learning disability and seizures.
      Despite a low risk of recurrence for small supernumerary marker chromosomes the
      possibility of germ line mosaicism exists, thus genetic counseling was offered to
      the examined family. CONCLUSION: A full characterization of small supernumerary
      marker chromosomes in fetal karyotype is necessary for pregnancy prognosis and
      genetic counseling.

PMID- 25852031
TI  - What isn't said.

PMID- 25852030
TI  - Construction and validation of the My Medicines and Me Questionnaire for
      assessment of the self-reported side effects of psychotropic medication.
AB  - We aimed to construct and assess the psychometric properties of the My Medicines
      and Me Questionnaire (M3Q), a self-report side-effect questionnaire for mental
      health patients. Thirty individuals taking a psychotropic medication completed
      the M3Q side-effect checklist along with the Liverpool University Neuroleptic
      Side Effect Rating Scale. Thirty healthy comparison individuals also completed
      the M3Q checklist. Data were analyzed using factorial analysis. Psychometric
      evaluations including validity and reliability testing were carried out on the
      questionnaire's checklist. The original 54-item checklist of the M3Q was
      shortened to include only those items found to be significant in the factorial
      analysis. The revised 32-item checklist of the M3Q was found to be valid and
      reliable. The M3Q is a simple, valid and reliable questionnaire that can be used
      routinely in clinical practice for detecting bothersome side effects of a range
      of psychotropic medications. This will provide a platform for improved
      communication between the clinician and the patient. 

PMID- 25852032
TI  - Doctors urged to improve Aboriginal child health.

PMID- 25852033
TI  - Advancing social media in medical education.

PMID- 25852034
TI  - Nova Scotia sets direction on GPS monitoring of patients.

PMID- 25852035
TI  - Health professionalism must be ensured online and offline.

PMID- 25852036
TI  - Peanut and fish allergy due to platelet transfusion in a child.

PMID- 25852037
TI  - Elder abuse: an approach to identification, assessment and intervention.

PMID- 25852038
TI  - The resurgence of pertussis.

PMID- 25852039
TI  - Is Canada's drug safety network effective?

PMID- 25852041
TI  - Catalysts of worker-to-worker violence and incivility in hospitals.
AB  - AIMS AND OBJECTIVES: To identify common catalysts of worker-to-worker violence
      and incivility in hospital settings. BACKGROUND: Worker-to-worker violence and
      incivility are prevalent forms of mistreatment in healthcare workplaces. These
      are forms of counterproductive work behaviour that can lead to negative outcomes
      for employees, patients and the organisation overall. Identifying the factors
      that lead to co-worker mistreatment is a critical first step in the development
      of interventions targeting these behaviours. DESIGN: Retrospective descriptive
      study. METHODS: Qualitative content analysis was conducted on the total sample (n
      = 141) of employee incident reports of worker-to-worker violence and incivility
      that were documented in 2011 at a large American hospital system. RESULTS: More
      than 50% of the incidents involved nurses, and the majority of incidents did not
      involve physical violence. Two primary themes emerged from the analysis: Work
      Behaviour and Work Organisation. Incidents in the Work Behaviour category were
      often sparked by unprofessional behaviour, disagreement over responsibilities for
      work tasks or methods of patient care, and dissatisfaction with a co-worker's
      performance. Incidents in the Work Organisation category involved conflicts or
      aggression arising from failure to following protocol, patient assignments,
      limited resources and high workload. CONCLUSION: Incidents of worker-to-worker
      violence and incivility stemmed from dissatisfaction with employee behaviour or
      from organisational practices or work constraints. These incident descriptions
      reflect worker dissatisfaction and frustration, resulting from poor communication
      and collaboration between employees, all of which threaten work productivity.
      RELEVANCE TO CLINICAL PRACTICE: Violence and incivility between hospital
      employees can contribute to turnover of top performers, hinder effective teamwork
      and jeopardise the quality of patient care. Identification of common catalysts
      for worker-to-worker violence and incivility informs the development of
      mistreatment prevention programmes that can be used to educate hospital staff.

PMID- 25852042
TI  - Complex surgical therapy of multiple trichoepitheliomas.

PMID- 25852043
TI  - Atom-precise polyoxometalate-ag2 s core-shell nanoparticles.
AB  - Atomically precise polyoxometalate-Ag2 S core-shell nanoparticles were generated
      in a top-down approach under solvothermal conditions and structurally confirmed
      by X-ray single-crystal diffraction as an interesting core-shell structure
      comprising an in situ generated Mo6 O22 (8-) polyoxometalate core and a mango
      like Ag58 S38 shell. This result demonstrates the possibility to integrate
      polyoxometalate and Ag2 S nanoparticles into a core-shell heteronanostructure
      with precisely controlled atomical compositions of both core and shell. 

PMID- 25852044
TI  - Chronic helminth infection and helminth-derived egg antigens promote adipose
      tissue M2 macrophages and improve insulin sensitivity in obese mice.
AB  - Chronic low-grade inflammation associated with obesity contributes to insulin
      resistance and type 2 diabetes. Helminth parasites are the strongest natural
      inducers of type 2 immune responses, and short-lived infection with rodent
      nematodes was reported to improve glucose tolerance in obese mice. Here, we
      investigated the effects of chronic infection (12 weeks) with Schistosoma
      mansoni, a helminth that infects millions of humans worldwide, on whole-body
      metabolic homeostasis and white adipose tissue (WAT) immune cell composition in
      high-fat diet-induced obese C57BL/6 male mice. Our data indicate that chronic
      helminth infection reduced body weight gain (-62%), fat mass gain (-89%), and
      adipocyte size; lowered whole-body insulin resistance (-23%) and glucose
      intolerance (-16%); and improved peripheral glucose uptake (+25%) and WAT insulin
      sensitivity. Analysis of immune cell composition by flow cytometry and
      quantitative PCR (qPCR) revealed that S. mansoni promoted strong increases in WAT
      eosinophils and alternatively activated (M2) macrophages. Importantly, injections
      with S. mansoni-soluble egg antigens (SEA) recapitulated the beneficial effect of
      parasite infection on whole-body metabolic homeostasis and induced type 2 immune
      responses in WAT and liver. Taken together, we provide novel data suggesting that
      chronic helminth infection and helminth-derived molecules protect against
      metabolic disorders by promoting a T helper 2 (Th2) response, eosinophilia, and
      WAT M2 polarization.

PMID- 25852045
TI  - Alcohol Prevention and School Students: Findings From an Australian 2-Year Trial
      of Integrated Harm Minimization School Drug Education.
AB  - The Drug Education in Victorian Schools program provided integrated education
      about licit and illicit drugs, employed a harm minimization approach that
      incorporated participatory, critical thinking and skill-based teaching methods,
      and engaged parental influence through home activities. A cluster-randomized,
      controlled trial of the program was conducted with a student cohort during Year 8
      (13 years) and Year 9 (14 years). Twenty-one secondary schools in Victoria,
      Australia, were randomly allocated to the Drug Education in Victorian Schools
      program (14 schools, n = 1,163) or their usual drug education program (7 schools,
      n = 589). This study reports program effects for alcohol. There was a greater
      increase in the intervention students' knowledge about drugs, including alcohol;
      there was a greater increase in communication with parents about alcohol; they
      recalled receiving more alcohol education; their alcohol consumption increased
      less; and they experienced a lesser increase in alcohol-related harms. Among
      intervention group risky drinkers, consumption and harm increased less. There
      were no differences between study groups in attitudes toward alcohol or in the
      proportion of drinkers or risky drinkers. While the program did not stop students
      taking up drinking, it did reduce their consumption and harm. 

PMID- 25852046
TI  - Complex abdominopelvic endometriosis: the radiologist's perspective.
AB  - Endometriosis is a multifocal gynecological disorder affecting approximately 6%
      10% of women during their reproductive years (Giudice and Kao in: Lancet 364:1789
      1799, 2004). Presenting symptomatology often relates to the anatomical structures
      involved. Given the complexity of both the management and pain control of
      patients with complex endometriosis, the British Society of Gynaecological
      Endoscopy has issued guidelines on the establishment of a multidisciplinary team
      approach to these cases (http://www.bsge.org.uk/ec-requirements-BSGE-accredited
      endometriosis-centre.php). The ovaries are the most common site affected, but the
      gastrointestinal, genitourinary tract, chest and other soft tissues are not
      infrequently involved. Less well-recognized features of the disease include the
      deep infiltrative form of endometriosis, malignant transformation and
      decidualization of endometriomas under progesterone. In this pictorial essay, we
      will discuss the clinical presentation and review the imaging features of these
      complex and under appreciated forms of endometriotic disease.

PMID- 25852047
TI  - CT-based assessment of renal function impairment in patients with acute
      unilateral ureteral obstruction by urinary stones.
AB  - PURPOSE: The purpose of our study was to evaluate computed tomography (CT)
      imaging factors related to renal function impairment in patients with acute
      unilateral ureteral obstruction by urinary stones. MATERIALS AND METHODS: The
      study included 94 patients who had acute unilateral ureteral obstruction due to a
      urinary stone and a normal contralateral kidney. We retrospectively investigated
      the serum creatinine (SCr) levels immediately prior to CT examination and at
      least 1 week after treatment. CT examinations were performed using a CT urography
      protocol, including pre- and post-contrast images. The 67 patients with a SCr
      change of less than 0.3 mg/dL constituted group A. The other 27 patients with a
      SCr decrease of more than 0.3 mg/dL constituted group B. To evaluate factors
      related to renal function impairment, differences in CT imaging factors between
      the two groups, including the cortical and medullary density, renal and pelvic
      anteroposterior diameter, and perinephric fluid, were statistically analyzed.
      RESULTS: The SCr immediately prior to CT examination significantly differed
      between the two groups. The follow-up SCr after resolution did not significantly
      differ between the two groups. The difference in the mean cortical and medullary
      HU on the nephrographic phase between the obstructed kidney and normal kidney was
      higher in group B than in group A (27.1 +/- 23.1 and 69.4 +/- 59.1 vs. 5.7 +/-
      8.8 and 31.8 +/- 34.8; p < 0.001 and p = 0.004, respectively). The cut-off point
      for the difference in the mean cortical HU on the nephrographic phase between the
      obstructed kidney and normal kidney for renal function impairment was 15 HU, as
      determined by a receiver operating characteristic curve analysis. CONCLUSIONS:
      Patients with significantly impaired renal function due to an acute unilateral
      ureteral obstruction may show a decreased nephrogram of the affected kidney and a
      significant difference in the HU on the nephrographic phase between the
      obstructed and normal kidney.

PMID- 25852048
TI  - Herlyn-Werner-Wunderlich syndrome: pre- and post-surgical MRI and US findings.
AB  - Herlyn-Werner-Wunderlich syndrome (HWWS) is a rare congenital anomaly of the
      female urogenital tract that associates Mullerian duct anomalies with mesonephric
      duct anomalies. The triad of uterus didelphys, obstructed hemivagina, and
      ipsilateral renal agenesis characterizes this syndrome. Patients generally
      present with non-specific symptoms after menarche. Pelvic pain, dysmenorrhea, and
      palpable mass due to hematocolpos or hematometra are the most common findings.
      Pyohematocolpos and pyosalpinx may appear as acute complications, while
      endometriosis and pelvic adhesions constitute potential long-term complications.
      When a prenatal diagnosis of unilateral renal agenesis in newborn girls is known,
      a gynecological imaging study should be performed to exclude uterine and vaginal
      abnormalities. These patients should be followed up to ensure that a timely
      surgical correction is performed. The diagnosis of HWWS is difficult due to the
      lack of specific symptoms or findings upon physical examination. An accurate
      imaging description of these congenital anomalies is crucial to guide patients
      toward surgical treatment, relieving acute complications, and preserving the
      normal fertility. The authors provide a pictorial review of the magnetic
      resonance imaging and ultrasonography findings of the HWWS with correlation to
      embryological, clinical, and surgical features. 

PMID- 25852049
TI  - Employers' attitudes on hiring workers with intellectual disabilities in small
      and medium enterprises: an Italian research.
AB  - Employers play a significant role in the process of hiring workers with
      intellectual disability. Through an in-depth interview, this research aims to
      investigate the attitudes of 30 representatives of small and medium-sized Italian
      companies involved in a process of recruitment. The data were analyzed using a
      phenomenological approach. The results show that attitudes toward the disabled
      employee are influenced by three areas, namely, personal characteristics of
      employers, selection process, and concerns and opinions of employers. 

PMID- 25852050
TI  - Cumulative dose of hydroxychloroquine is associated with a decrease of resting
      heart rate in patients with systemic lupus erythematosus: a pilot study.
AB  - INTRODUCTION: The use of hydroxychloroquine (HCQ) in patients with systemic lupus
      erythematosus (SLE) offers a wide range of benefits. However, there are evidence
      in favour of cardiotoxicity, including heart conduction disturbances and
      congestive heart failure. OBJECTIVE: To determine the effects of HCQ in the
      resting heart rate (RHR) of SLE patients. PATIENTS AND METHODS: Included were
      patients with non active SLE, with a sedentary lifestyle and treated with HCQ.
      Excluded were patients on beta blocker treatment, trained patients, pacemaker's
      users and patients with clinical or analytical evidence of anemia, renal disease,
      obstructive pulmonary disease, obesity, uncontrolled thyroid disease, fever or
      current infection. Standard 12-lead electrocardiogram was performed in the
      resting condition (supine decubitus and orthostatic position). Comparison between
      groups was performed using Mann-Whitney U test. A multiple linear regression was
      performed. A p value <0.05 was considered statistically significant. RESULTS: 42
      patients were included. Patients were divided in two groups based on the
      cumulative dose of HCQ (CD-HCQ), considering 365 g as cut-off. There were 24
      patients with low-HCQ (<365 g) and 18 patients with high-HCQ (>365 g). Non
      significant differences were found in age, sex, prednisone dose or SLEDAI. The
      mean RHR was 73 +/- 6 beats/min in the low-HCQ and 65 +/- 7 beats/min in the high
      HCQ, with a significant decrease of 11% (p = 0.003). In multiple linear
      regressions, there were non significant association between the decrease of RHR
      and prednisone dose, age, SLEDAI or TSH, but there was significant association
      between RHR and CD-HCQ (p = 0.024) and RHR and time of exposure to HCQ (p =
      0.029). CONCLUSION: CD-HCQ higher than 365 g was associated with a significant
      decrease (11%) in RHR in non-active SLE patients, although a larger prospective
      study is required to allow more definitive conclusions.

PMID- 25852051
TI  - Ach1 is involved in shuttling mitochondrial acetyl units for cytosolic C2
      provision in Saccharomyces cerevisiae lacking pyruvate decarboxylase.
AB  - Acetyl-coenzyme A (acetyl-CoA) is not only an essential intermediate in central
      carbon metabolism, but also an important precursor metabolite for native or
      engineered pathways that can produce many products of commercial interest such as
      pharmaceuticals, chemicals or biofuels. In the yeast Saccharomyces cerevisiae,
      acetyl-CoA is compartmentalized in the cytosol, mitochondrion, peroxisome and
      nucleus, and cannot be directly transported between these compartments. With the
      acetyl-carnitine or glyoxylate shuttle, acetyl-CoA produced in peroxisomes or the
      cytoplasm can be transported into the cytoplasm or the mitochondria. However,
      whether acetyl-CoA generated in the mitochondria can be exported to the cytoplasm
      is still unclear. Here, we investigated whether the transfer of acetyl-CoA from
      the mitochondria to the cytoplasm can occur using a pyruvate decarboxylase
      negative, non-fermentative yeast strain. We found that mitochondrial Ach1 can
      convert acetyl-CoA in this compartment into acetate, which crosses the
      mitochondrial membrane before being converted into acetyl-CoA in the cytosol.
      Based on our finding we propose a model in which acetate can be used to exchange
      acetyl units between mitochondria and the cytosol. These results will increase
      our fundamental understanding of intracellular transport of acetyl units, and
      also help to develop microbial cell factories for many kinds of acetyl-CoA
      derived products. 

PMID- 25852052
TI  - Comparative analysis of human ex vivo-generated platelets vs megakaryocyte
      generated platelets in mice: a cautionary tale.
AB  - Thrombopoiesis is the process by which megakaryocytes release platelets that
      circulate as uniform small, disc-shaped anucleate cytoplasmic fragments with
      critical roles in hemostasis and related biology. The exact mechanism of
      thrombopoiesis and the maturation pathways of platelets released into the
      circulation remain incompletely understood. We showed that ex vivo-generated
      murine megakaryocytes infused into mice release platelets within the pulmonary
      vasculature. Here we now show that infused human megakaryocytes also release
      platelets within the lungs of recipient mice. In addition, we observed a
      population of platelet-like particles (PLPs) in the infusate, which include
      platelets released during ex vivo growth conditions. By comparing these 2
      platelet populations to human donor platelets, we found marked differences:
      platelets derived from infused megakaryocytes closely resembled infused donor
      platelets in morphology, size, and function. On the other hand, the PLP was a
      mixture of nonplatelet cellular fragments and nonuniform-sized, preactivated
      platelets mostly lacking surface CD42b that were rapidly cleared by macrophages.
      These data raise a cautionary note for the clinical use of human platelets
      released under standard ex vivo conditions. In contrast, human platelets released
      by intrapulmonary-entrapped megakaryocytes appear more physiologic in nature and
      nearly comparable to donor platelets for clinical application. 

PMID- 25852053
TI  - The role of stem cell transplantation for chronic myelogenous leukemia in the
      21st century.
AB  - The introduction of tyrosine kinase inhibitors (TKIs), a treatment of chronic
      myelogenous leukemia (CML), has largely replaced curative strategies based on
      allogeneic stem cell transplantation (SCT). Nevertheless, SCT still remains an
      option for accelerated/blastic-phase and selected chronic-phase CML. Transplant
      outcomes can be optimized by peritransplant TKIs, conditioning regimen, BCR-ABL
      monitoring, and relapse management. Controversies exist in transplant timing,
      pediatric CML, alternative donors, and economics. SCT continues to serve as a
      platform of "operational cure" for CML with TKIs and immunotherapies. 

PMID- 25852054
TI  - CMV reactivation drives posttransplant T-cell reconstitution and results in
      defects in the underlying TCRbeta repertoire.
AB  - Although cytomegalovirus (CMV) reactivation has long been implicated in
      posttransplant immune dysfunction, the molecular mechanisms that drive this
      phenomenon remain undetermined. To address this, we combined multiparameter flow
      cytometric analysis and T-cell subpopulation sorting with high-throughput
      sequencing of the T-cell repertoire, to produce a thorough evaluation of the
      impact of CMV reactivation on T-cell reconstitution after unrelated-donor
      hematopoietic stem cell transplant. We observed that CMV reactivation drove a >50
      fold specific expansion of Granzyme B(high)/CD28(low)/CD57(high)/CD8(+) effector
      memory T cells (Tem) and resulted in a linked contraction of all naive T cells,
      including CD31(+)/CD4(+) putative thymic emigrants. T-cell receptor beta
      (TCRbeta) deep sequencing revealed a striking contraction of CD8(+) Tem diversity
      due to CMV-specific clonal expansions in reactivating patients. In addition to
      querying the topography of the expanding CMV-specific T-cell clones, deep
      sequencing allowed us, for the first time, to exhaustively evaluate the
      underlying TCR repertoire. Our results reveal new evidence for significant
      defects in the underlying CD8 Tem TCR repertoire in patients who reactivate CMV,
      providing the first molecular evidence that, in addition to driving expansion of
      virus-specific cells, CMV reactivation has a detrimental impact on the integrity
      and heterogeneity of the rest of the T-cell repertoire. This trial was registered
      at www.clinicaltrials.gov as #NCT01012492. 

PMID- 25852056
TI  - How I treat refractory and early relapsed acute myeloid leukemia.
AB  - Between 10% and 40% of newly diagnosed patients with acute myeloid leukemia (AML)
      do not achieve complete remission with intensive induction therapy and are
      therefore categorized as primary refractory or resistant. Few of these patients
      can be cured with conventional salvage therapy. They need to be evaluated
      regarding eligibility for allogeneic hematopoietic stem cell transplantation
      (HSCT) as this is currently the treatment with the highest probability of cure.
      To reduce the leukemia burden prior to transplantation, salvage chemotherapy
      regimens need to be employed. Whenever possible, refractory/relapsed patients
      should be enrolled in clinical trials as we do not have highly effective and
      standardized treatments for this situation. Novel therapies include tyrosine
      kinase inhibitors, small-molecule inhibitors (e.g., for Polo-like kinase 1 and
      aminopeptidase), inhibitors of mutated isocitrate dehydrogenase (IDH) 1 and IDH2,
      antibody-based therapies, and cell-based therapies. Although the majority of
      these therapies are still under evaluation, they are likely to enter clinical
      practice rapidly as a bridge to transplant and/or in older, unfit patients who
      are not candidates for allogeneic HSCT. In this review, we describe our approach
      to refractory/early relapsed AML, and we discuss treatment options for patients
      with regard to different clinical conditions and molecular profiles.

PMID- 25852055
TI  - Characteristic repartition of monocyte subsets as a diagnostic signature of
      chronic myelomonocytic leukemia.
AB  - Chronic myelomonocytic leukemia (CMML) is a myelodysplastic syndrome/
      myeloproliferative neoplasm whose diagnosis is currently based on the elevation
      of peripheral blood monocytes to >1 * 10(9)/L, measured for >=3 months. Diagnosis
      can be ambiguous; for example, with prefibrotic myelofibrosis or reactive
      monocytosis. We set up a multiparameter flow cytometry assay to distinguish
      CD14(+)/CD16(-) classical from CD14(+)/CD16(+) intermediate and CD14(low)/CD16(+)
      nonclassical monocyte subsets in peripheral blood mononucleated cells and in
      total blood samples. Compared with healthy donors and patients with reactive
      monocytosis or another hematologic malignancy, CMML patients demonstrate a
      characteristic increase in the fraction of CD14(+)/CD16(-) cells (cutoff value,
      94.0%). The associated specificity and sensitivity values were 95.1% and 90.6% in
      the learning cohort (175 samples) and 94.1% and 91.9% in the validation cohort
      (307 samples), respectively. The accumulation of classical monocytes, which
      demonstrate a distinct gene expression pattern, is independent of the mutational
      background. Importantly, this increase disappears in patients who respond to
      hypomethylating agents. We conclude that an increase in the fraction of classical
      monocytes to >94.0% of total monocytes is a highly sensitive and specific
      diagnostic marker that rapidly and accurately distinguishes CMML from confounding
      diagnoses. 

PMID- 25852057
TI  - Targeting Syk-activated B cells in murine and human chronic graft-versus-host
      disease.
AB  - Novel therapies for chronic graft-versus-host disease (cGVHD) are needed.
      Aberrant B-cell activation has been demonstrated in mice and humans with cGVHD.
      Having previously found that human cGVHD B cells are activated and primed for
      survival, we sought to further evaluate the role of the spleen tyrosine kinase
      (Syk) in cGVHD in multiple murine models and human peripheral blood cells. In a
      murine model of multiorgan system, nonsclerodermatous disease with bronchiolitis
      obliterans where cGVHD is dependent on antibody and germinal center (GC) B cells,
      we found that activation of Syk was necessary in donor B cells, but not T cells,
      for disease progression. Bone marrow-specific Syk deletion in vivo was effective
      in treating established cGVHD, as was a small-molecule inhibitor of Syk,
      fostamatinib, which normalized GC formation and decreased activated CD80/86(+)
      dendritic cells. In multiple distinct models of sclerodermatous cGVHD, clinical
      and pathological disease manifestations were not eliminated when mice were
      therapeutically treated with fostamatinib, though both clinical and immunologic
      effects could be observed in one of these scleroderma models. We further
      demonstrated that Syk inhibition was effective at inducing apoptosis of human
      cGVHD B cells. Together, these data demonstrate a therapeutic potential of
      targeting B-cell Syk signaling in cGVHD. 

PMID- 25852059
TI  - On the Road to Precision Cancer Medicine: Analysis of Genomic Biomarker
      Actionability in 439 Patients.
AB  - Despite the increased use of molecular diagnostics, the extent to which patients
      who have these tests harbor potentially actionable aberrations is unclear. We
      retrospectively reviewed 439 patients with diverse cancers, for whom next
      generation sequencing (mostly 236-gene panel) had been performed. Data pertaining
      to the molecular alterations identified, as well as associated treatment
      suggestions (on- or off-label, or experimental), were extracted from molecular
      diagnostic reports. Most patients (420/439; 96%) had at least one molecular
      alteration: 1,813 alterations (in 207 distinct genes) were identified [the
      majority being mutations (62%) or amplifications (29%)]. The three most common
      gene abnormalities were TP53 (44%), KRAS (16%), and PIK3CA (12%). The median
      number of alterations per patient was 3 (range, 0-16). Nineteen patients (4%) had
      no alterations; 48 patients (11%) had only one alteration; and 372 patients had
      two or more abnormalities (85%). The median number of potentially actionable
      anomalies per patient was 2 (range, 0-8). Most patients (393/439; 90%) had at
      least one potentially actionable alteration, and in all these cases the
      aberration could at least be targeted by an experimental drug in a clinical
      trial. A total of 307 patients (70%) had an alteration that was actionable with
      an approved drug, but in only 89 patients (20%) was the drug approved for their
      disease (on-label). Next-generation sequencing identified theoretically
      actionable aberrations in 90% of our patients. Many of the drugs are, however,
      experimental or would require off-label use. Strategies to address drug access
      for patients harboring potentially actionable mutations are needed.

PMID- 25852058
TI  - CDKN2A/p16 Loss Implicates CDK4 as a Therapeutic Target in Imatinib-Resistant
      Dermatofibrosarcoma Protuberans.
AB  - Dermatofibrosarcoma protuberans (DFSP) is an aggressive PDGFB-dependent cutaneous
      sarcoma characterized by infiltrative growth and frequent local recurrences. Some
      DFSP progress to a higher-grade fibrosarcomatous form, with rapid growth and
      increased risk of metastasis. Imatinib provides clinical benefit in approximately
      50% of patients with unresectable or metastatic DFSP. However, efficacious
      medical therapies have not been developed for imatinib-resistant DFSP. We
      established a model of imatinib-resistant DFSP and evaluated CDK4/6 inhibition as
      a genomically credentialed targeted therapy. DFSP105, an imatinib-resistant human
      cell line, was established from a fibrosarcomatous DFSP (FS-DFSP), and was
      studied by SNP arrays and sequencing to identify targetable genomic alterations.
      Findings were validated in vitro and in vivo, and confirmed in a series including
      12 DFSP and 6 FS-DFSP. SNP analysis of DFSP105 revealed a homozygous deletion
      encompassing CDKN2A and CDKN2B. The resultant p16 loss implicated CDK4/6 as a
      potential therapeutic target in DFSP. We further demonstrated CDKN2A homozygous
      deletion in 1 of 12 conventional DFSP and 2 of 6 FS-DFSP, whereas p16 expression
      was lost in 4 of 18 DFSP. In vitro treatment of DFSP105 with two structurally
      distinct selective CDK4/6 inhibitors, PD-0332991 and LEE011, led to inhibition of
      RB1 phosphorylation and inhibition of proliferation (GI50 160 nmol/L and 276
      nmol/L, respectively). In vivo treatment of DFSP105 with PD-0332991 (150 mg/kg)
      inhibited xenograft growth in mice, in comparison with imatinib-treated or 
      untreated tumors. In conclusion, CDKN2A deletion can contribute to DFSP
      progression. CDK4/6 inhibition is a preclinically effective treatment against p16
      negative, imatinib-resistant FS-DFSP, and should be evaluated as a therapeutic
      strategy in patients with unresectable or metastatic imatinib-resistant DFSP.

PMID- 25852060
TI  - Effective Targeting of Estrogen Receptor-Negative Breast Cancers with the Protein
      Kinase D Inhibitor CRT0066101.
AB  - Invasive ductal carcinomas (IDC) of the breast are associated with altered
      expression of hormone receptors (HR), amplification or overexpression of HER2, or
      a triple-negative phenotype. The most aggressive cases of IDC are characterized
      by a high proliferation rate, a great propensity to metastasize, and their
      ability to resist to standard chemotherapy, hormone therapy, or HER2-targeted
      therapy. Using progression tissue microarrays, we here demonstrate that the
      serine/threonine kinase protein kinase D3 (PKD3) is highly upregulated in
      estrogen receptor (ER)-negative (ER(-)) tumors. We identify direct binding of the
      ER to the PRKD3 gene promoter as a mechanism of inhibition of PKD3 expression.
      Loss of ER results in upregulation of PKD3, leading to all hallmarks of
      aggressive IDC, including increased cell proliferation, migration, and invasion.
      This identifies ER(-) breast cancers as ideal for treatment with the PKD
      inhibitor CRT0066101. We show that similar to a knockdown of PKD3, treatment with
      this inhibitor targets all tumorigenic processes in vitro and decreases growth of
      primary tumors and metastasis in vivo. Our data strongly support the development
      of PKD inhibitors for clinical use for ER(-) breast cancers, including the triple
      negative phenotype.

PMID- 25852061
TI  - Recruitment of Oligoclonal Viral-Specific T cells to Kill Human Tumor Cells Using
      Single-Chain Antibody-Peptide-HLA Fusion Molecules.
AB  - Tumor progression is often associated with the development of diverse immune
      escape mechanisms. One of the main tumor escape mechanism is HLA loss, in which
      human solid tumors exhibit alterations in HLA expression. Moreover, tumors that
      present immunogenic peptides via class I MHC molecules are not susceptible to CTL
      mediated lysis, because of the relatively low potency of the tumor-specific CLTs.
      Here, we present a novel cancer immunotherapy approach that overcomes these
      problems by using the high affinity and specificity of antitumor antibodies to
      recruit potent antiviral memory CTLs to attack tumor cells. We constructed a
      recombinant molecule by genetic fusion of a cytomegalovirus (CMV)-derived peptide
      pp65 (NLVPMVATV) to scHLA-A2 molecules that were genetically fused to a single
      chain Fv Ab fragment specific for the tumor cell surface antigen mesothelin. This
      fully covalent fusion molecule was expressed in E. coli as inclusion bodies and
      refolded in vitro. The fusion molecules could specifically bind mesothelin
      expressing cells and mediate their lysis by NLVPMVATV-specific HLA-A2-restricted
      human CTLs. More importantly, these molecules exhibited very potent antitumor
      activity in vivo in a nude mouse model bearing preestablished human tumor
      xenografts that were adoptively transferred along with human memory CTLs. These
      results represent a novel and powerful approach to immunotherapy for solid
      tumors, as demonstrated by the ability of the CMV-scHLA-A2-SS1(scFv) fusion
      molecule to mediate specific and efficient recruitment of CMV-specific CTLs to
      kill tumor cells.

PMID- 25852062
TI  - Enhanced GAB2 Expression Is Associated with Improved Survival in High-Grade
      Serous Ovarian Cancer and Sensitivity to PI3K Inhibition.
AB  - Identification of genomic alterations defining ovarian carcinoma subtypes may aid
      the stratification of patients to receive targeted therapies. We characterized
      high-grade serous ovarian carcinoma (HGSC) for the association of amplified and
      overexpressed genes with clinical outcome using gene expression data from 499
      HGSC patients in the Ovarian Tumor Tissue Analysis cohort for 11 copy number
      amplified genes: ATP13A4, BMP8B, CACNA1C, CCNE1, DYRK1B, GAB2, PAK4, RAD21, TPX2,
      ZFP36, and URI. The Australian Ovarian Cancer Study and The Cancer Genome Atlas
      datasets were also used to assess the correlation between gene expression,
      patient survival, and tumor classification. In a multivariate analysis, high GAB2
      expression was associated with improved overall and progression-free survival (P
      = 0.03 and 0.02), whereas high BMP8B and ATP13A4 were associated with improved
      progression-free survival (P = 0.004 and P = 0.02). GAB2 overexpression and copy
      number gain were enriched in the AOCS C4 subgroup. High GAB2 expression
      correlated with enhanced sensitivity in vitro to the dual PI3K/mTOR inhibitor PF
      04691502 and could be used as a genomic marker for identifying patients who will
      respond to treatments inhibiting PI3K signaling.

PMID- 25852063
TI  - Selective Delivery of PEGylated Compounds to Tumor Cells by Anti-PEG Hybrid
      Antibodies.
AB  - Polyethylene glycol (PEG) is attached to many peptides, proteins, liposomes, and
      nanoparticles to reduce their immunogenicity and improve their pharmacokinetic
      and therapeutic properties. Here, we describe hybrid antibodies that can
      selectively deliver PEGylated medicines, imaging agents, or nanomedicines to
      target cells. Human IgG1 hybrid antibodies alphaPEG:alphaHER2 and
      alphaPEG:alphaCD19 were shown by ELISA, FACS, and plasmon resonance to bind to
      both PEG and HER2 receptors on SK-BR-3 breast adenocarcinoma and BT-474 breast
      ductal carcinoma cells or CD19 receptors on Ramos and Raji Burkitt's lymphoma
      cells. In addition, alphaPEG:alphaHER2 specifically targeted PEGylated proteins,
      liposomes, and nanoparticles to SK-BR-3 cells that overexpressed HER2, but not to
      HER2-negative MCF-7 breast adenocarcinoma cells. Endocytosis of PEGylated
      nanoparticles into SK-BR-3 cells was induced specifically by the
      alphaPEG:alphaHER2 hybrid antibody, as observed by confocal imaging of the
      accumulation of Qdots inside SK-BR-3 cells. Treatment of HER2(+) SK-BR-3 and BT
      474 cancer cells with alphaPEG:alphaHER2 and the clinically used chemotherapeutic
      agent PEGylated liposomal doxorubicin for 3 hours enhanced the in vitro
      effectiveness of PEGylated liposomal doxorubicin by over two orders of magnitude.
      Hybrid anti-PEG antibodies offer a versatile and simple method to deliver
      PEGylated compounds to cellular locations and can potentially enhance the
      therapeutic efficacy of PEGylated medicines.

PMID- 25852064
TI  - Physical therapy is as effective as surgery for lumbar spinal stenosis, study
      finds.

PMID- 25852065
TI  - Aquatic burst locomotion by hydroplaning and paddling in common eiders (Somateria
      mollissima).
AB  - Common eiders (Somateria mollissima) are heavy sea-ducks that spend a large
      portion of their time swimming at the water surface. Surface swimming generates a
      bow and hull wave that can constructively interfere and produce wave drag. The
      speed at which the wavelengths of these waves equal the waterline length of the
      swimming animal is the hull speed. To increase surface swimming speed beyond the
      hull speed, an animal must overtake the bow wave. This study found two distinct
      behaviors that eider ducks used to exceed the hull speed: (1) 'steaming', which
      involved rapid oaring with the wings to propel the duck along the surface of the
      water, and (2) 'paddle-assisted flying', during which the ducks lifted their
      bodies out of the water and used their feet to paddle against the surface while
      flapping their wings in the air. An average hull speed (0.732+/-0.046 m s(-1))
      was calculated for S. mollissima by measuring maximum waterline length from
      museum specimens. On average, steaming ducks swam 5.5 times faster and paddle
      assisted flying ducks moved 6.8 times faster than the hull speed. During
      steaming, ducks exceeded the hull speed by increasing their body angle and
      generating dynamic lift to overcome wave drag and hydroplane along the water
      surface. During paddle-assisted flying, ducks kept their bodies out of the water,
      thereby avoiding the limitations of wave drag altogether. Both behaviors provided
      alternatives to flight for these ducks by allowing them to exceed the hull speed
      while staying at or near the water surface. 

PMID- 25852066
TI  - Mechanisms and costs of mitochondrial thermal acclimation in a eurythermal
      killifish (Fundulus heteroclitus).
AB  - Processes acting at the level of the mitochondria have been suggested to affect
      the thermal limits of organisms. To determine whether changes in mitochondrial
      properties could underlie shifts in thermal limits, we examined how mitochondrial
      properties are affected by thermal acclimation in the eurythermal killifish,
      Fundulus heteroclitus - a species with substantial plasticity in whole-organism
      thermal limits. We hypothesized that thermal acclimation would result in
      functional changes in the mitochondria that could result in trade-offs in
      function during acute thermal shifts. We measured the mitochondrial respiration
      rate (VO2 ) through multiple complexes of the electron transport system following
      thermal acclimation (to 5, 15, 33 degrees C) and assessed maintenance of
      mitochondrial membrane potential (Deltap) and rates of reactive oxygen species
      (ROS) production as an estimate of costs. Acclimation to 5 degrees C resulted in
      a modest compensation of mitochondrial respiration at low temperatures, but these
      mitochondria were able to maintain Deltap with acute exposure to high
      temperatures, and ROS production did not differ between acclimation groups,
      suggesting that these increases in mitochondrial capacity do not alter
      mitochondrial thermal sensitivity. Acclimation to 33 degrees C suppressed
      mitochondrial respiration as a result of effects on NADH dehydrogenase (complex
      I). These high-temperature acclimated fish nonetheless maintained levels of
      Deltap and ROS production similar to those of the other acclimation groups. This
      work demonstrates that killifish mitochondria can successfully acclimate to a
      wide range of temperatures without incurring major functional trade-offs during
      acute thermal shifts and that high-temperature acclimation results in a
      suppression of metabolism, consistent with patterns observed at the organismal
      level. 

PMID- 25852067
TI  - Behaviour of the plathelminth Symsagittifera roscoffensis under different light
      conditions and the consequences for the symbiotic algae Tetraselmis convolutae.
AB  - Symsagittifera roscoffensis is a plathelminth living in symbiosis with the green
      algae Tetraselmis convolutae. Host and symbiont are a model system for the study
      of endosymbiosis, which has so far mainly focused on their biochemical
      interactions. Symsagittifera roscoffensis is well known for its positive
      phototaxis that is hypothesized to optimize the symbiont's light perception for
      photosynthesis. In this study, we conducted a detailed analysis of phototaxis
      using light sources of different wavelength and brightness by videotracking.
      Furthermore, we compared the behavioural data with the electron transfer rate of
      the photosystem from cultured symbiotic cells. The symbiotic algae is adapted to
      low light conditions, showing a positive electron transfer rate at a
      photosynthetically active radiation of 0.112 umol photons m(-2) s(-1), and S.
      roscoffensis showed a positive phototactic behaviour for light intensities up to
      459.17 umol photons m(-2) s(-1), which is not optimal regarding the needs of the
      symbiotic cells and may even harm host and symbiont. Red light cannot be detected
      by the animals and therefore their eyes seem not to be suitable for measuring the
      exact photosynthetically active radiation to the benefit of the photosymbionts. 

PMID- 25852068
TI  - Body mass affects seasonal variation in sickness intensity in a seasonally
      breeding rodent.
AB  - Species that display seasonal variation in sickness intensity show the most
      intense response in the season during which they have the highest body mass,
      suggesting that sickness intensity may be limited by an animal's energy stores.
      Siberian hamsters (Phodopus sungorus) display lower body masses and less intense
      sickness when housed in short, winter-like days as opposed to long, summer-like
      days. To determine whether reduced sickness intensity displayed by short-day
      hamsters is a product of seasonal changes in body mass, we food restricted long
      day hamsters so that they exhibited body mass loss that mimicked the natural
      photoperiod-induced loss of body mass in short-day hamsters. We then
      experimentally induced sickness with lipopolysaccharide (LPS) and compared
      sickness responses among long-day food-restricted and long- and short-day ad
      libitum fed groups, predicting that long-day food-restricted hamsters would show
      sickness responses comparable to those of short-day ad libitum fed hamsters and
      attenuated in comparison to long-day ad libitum fed hamsters. We found that long
      day food-restricted hamsters showed attenuated LPS-induced anorexia, loss of body
      mass and hypothermia compared with long-day ad libitum fed animals; however,
      anorexia remained elevated in long-day food-restricted animals compared with
      short-day ad libitum fed animals. Additionally, LPS-induced anhedonia and
      decreases in nest building were not influenced by body mass. Results of hormone
      assays suggest that cortisol levels could play a role in the attenuation of
      sickness in long-day food-restricted hamsters, indicating that future research
      should target the roles of glucocorticoids and natural variation in energy stores
      in seasonal sickness variation. 

PMID- 25852069
TI  - Vocal performance affects metabolic rate in dolphins: implications for animals
      communicating in noisy environments.
AB  - Many animals produce louder, longer or more repetitious vocalizations to
      compensate for increases in environmental noise. Biological costs of increased
      vocal effort in response to noise, including energetic costs, remain empirically
      undefined in many taxa, particularly in marine mammals that rely on sound for
      fundamental biological functions in increasingly noisy habitats. For this
      investigation, we tested the hypothesis that an increase in vocal effort would
      result in an energetic cost to the signaler by experimentally measuring oxygen
      consumption during rest and a 2 min vocal period in dolphins that were trained to
      vary vocal loudness across trials. Vocal effort was quantified as the total
      acoustic energy of sounds produced. Metabolic rates during the vocal period were,
      on average, 1.2 and 1.5 times resting metabolic rate (RMR) in dolphin A and B,
      respectively. As vocal effort increased, we found that there was a significant
      increase in metabolic rate over RMR during the 2 min following sound production
      in both dolphins, and in total oxygen consumption (metabolic cost of sound
      production plus recovery costs) in the dolphin that showed a wider range of vocal
      effort across trials. Increases in vocal effort, as a consequence of increases in
      vocal amplitude, repetition rate and/or duration, are consistent with behavioral
      responses to noise in free-ranging animals. Here, we empirically demonstrate for
      the first time in a marine mammal, that these vocal modifications can have an
      energetic impact at the individual level and, importantly, these data provide a
      mechanistic foundation for evaluating biological consequences of vocal
      modification in noise-polluted habitats.

PMID- 25852070
TI  - Controlled feeding trials with ungulates: a new application of in vivo dental
      molding to assess the abrasive factors of microwear.
AB  - Microwear, the quantification of microscopic scratches and pits on the occlusal
      surfaces of tooth enamel, is commonly used as a paleodietary proxy. For ungulates
      (hoofed mammals), scratch-dominant microwear distinguishes modern grazers from
      browsers, presumably as a result of abrasion from grass phytoliths (biogenic
      silica). However, it is also likely that exogenous grit (i.e. soil, dust) is a
      contributing factor to these scratch-dominant patterns, which may reflect soil
      ingestion that varies with feeding height and/or environmental conditions (e.g.
      dust production in open and/or arid habitats). This study assessed the
      contribution of exogenous grit to tooth wear by measuring the effects of fine-
      and medium-grained silica sand on tooth enamel using a novel live-animal tooth
      molding technique. It therefore constitutes the first controlled feeding
      experiment using ungulates and the first in vivo experiment using abrasives of
      different sizes. Four sheep were fed three diet treatments: (1) a mixture of
      Garrison and Brome hay (control), (2) hay treated with fine-grained silica sand
      (180-250 um) and (3) hay treated with medium-grained silica sand (250-425 um). We
      found a significant increase in pit features that was correlated with an increase
      in grain size of grit, corroborating earlier chewing simulation experiments that
      produced pits through grit-induced abrasion (i.e. the 'grit effect'). Our results
      support an interpretation of large silica grains fracturing to create smaller,
      more abundant angular particles capable of abrasion, with jaw movement defining
      feature shape (i.e. scratch or pit). 

PMID- 25852071
TI  - Brainstem brain-derived neurotrophic factor signaling is required for histone
      deacetylase inhibitor-induced pain relief.
AB  - Our previous study demonstrated that persistent pain can epigenetically suppress
      the transcription of Gad2 [encoding glutamic acid decarboxylase 65 (GAD65)] and
      consequently impair the inhibitory function of GABAergic synapses in central pain
      modulating neurons. This contributes to the development of persistent pain
      sensitization. Histone deacetylase (HDAC) inhibitors increased GAD65 activity
      considerably, restored GABA synaptic function, and rendered sensitized pain
      behavior less pronounced. However, the molecular mechanisms by which HDAC
      regulates GABAergic transmission through GAD65 under pain conditions are unknown.
      This work showed that HDAC inhibitor-induced increases in colocalization of GAD65
      and synaptic protein synapsin I on the presynaptic axon terminals of the nucleus
      raphe magnus (NRM) were blocked by a TrkB receptor antagonist K252a [(9S,10R,12R)
      2,3,9,10,11,12-hexahydro-10-hydroxy-9-methyl-1-oxo-9,12-epoxy-1H-diindolo[1,2,3
      fg:3',2',1'-kl]pyrrolo[3,4-i][1,6]benzodiazocine-10-carboxylic acid methyl
      ester], indicating that BDNF-TrkB signaling may be required in GAD65 modulation
      of GABA synaptic function. At the brain-derived neurotrophic factor (BDNF)
      promoter, HDAC inhibitors induced significant increases in H3 hyperacetylation,
      consistent with the increase in BDNF mRNA and total proteins. Although exogenous
      BDNF facilitated GABA miniature inhibitory postsynaptic currents and GAD65
      accumulation in NRM neuronal synapses in normal rats, it failed to do so in
      animals subjected to persistent inflammation. In addition, blockade of the TrkB
      receptor with K252a has no effect on miniature inhibitory postsynaptic currents
      and synaptic GAD65 accumulation under normal conditions. In addition, the
      analgesic effects of HDAC inhibitors on behavior were blocked by NRM infusion of
      K252a. These findings suggest that BDNF-TrkB signaling is required for drugs that
      reverse the epigenetic effects of chronic pain at the gene level, such as HDAC
      inhibitors. 

PMID- 25852072
TI  - Intentional Large Insulin Overdose Captured on a Continuous Glucose Monitor: A
      Novel Case Report.

PMID- 25852073
TI  - Holistic Impact of Closed-Loop Technology on People With Type 1 Diabetes.

PMID- 25852074
TI  - Rate-of-Change Dependence of the Performance of Two CGM Systems During Induced
      Glucose Swings.
AB  - INTRODUCTION: The accuracy of continuous glucose monitoring (CGM) systems is
      often assessed with respect to blood glucose (BG) readings. CGM readings are
      affected by a physiological and a technical time delay when compared to BG
      readings. In this analysis, the dependence of CGM performance parameters on the
      BG rate of change was investigated for 2 CGM systems. METHODS: Data from a
      previously published study were retrospectively analyzed. An established CGM
      system (Dexcom G4, Dexcom, San Diego, CA; system A) and a prototype system (Roche
      Diagnostics GmbH, Mannheim, Germany; system B) with 2 sensors each were worn by
      10 subjects in parallel. Glucose swings were induced to achieve rapidly changing
      BG concentrations. Mean absolute relative differences (MARD) were calculated in
      different BG rate-of-change categories. In addition, sensor-to-sensor precision
      was assessed. RESULTS: At BG rates of change of -1 mg/dl/min to 0 mg/dl/min and 0
      mg/dl/min to +1 mg/dl/min, MARD results were 12.6% and 11.3% for system A and
      8.2% and 10.0% for system B. At rapidly changing BG concentrations (<-3 mg/dl/min
      and >=+3 mg/dl/min), higher MARD results were found for both systems, but system
      B was less affected (system A: 24.9% and 29.6%, system B: 10.6% and 16.3%). The
      impact of rate of change on sensor-to-sensor precision was less pronounced.
      CONCLUSIONS: Both systems were affected by rapidly changing BG concentrations to
      some degree, although system B was mostly unaffected by decreasing BG
      concentrations. It would seem that technological advancements in CGM systems
      might allow for a more precise tracking of BG concentrations even at rapidly
      changing BG concentrations.

PMID- 25852075
TI  - How to Assess the Quality of Glucose Clamps? Evaluation of Clamps Performed With
      ClampArt, a Novel Automated Clamp Device.
AB  - BACKGROUND: There are no widely accepted parameters to assess the quality of
      glucose clamps. Thus, we selected different parameters describing clamp quality.
      These parameters were then evaluated in glucose clamps carried out with ClampArt,
      a novel CE-marked, state-of-the-art fully automated glucose clamp device
      employing continuous blood glucose (BG) measurements and minute-by-minute
      adaptations of glucose infusion rate (GIR). METHODS: Thirty-nine glucose clamps
      were performed in 10 healthy and 29 subjects with type 1 diabetes (T1DM) (total
      duration 583 h). ClampArt-based BG measurements were compared with those obtained
      with a laboratory reference method. Clamp quality was assessed by 5 parameters:
      (1) difference (mg/dl) of all paired BG measurements of ClampArt versus reference
      method ("trueness"), (2) coefficient of variation (CV, %) of ClampArt's BG
      measurements at target clamp level ("precision"), (3) mean absolute relative
      difference (MARD, %) at target clamp level ("accuracy"), (4) difference (mg/dl)
      between ClampArt and target BG ("control deviation"), and (5) percentage
      operational time ("utility"). RESULTS: ClampArt-based BG measurements showed a
      trueness of 1.2 +/- 2.5 mg/dl. CV and MARD at target BG were 5.5 +/- 2.1% and 5.3
      +/- 2.3%, respectively. There were only small deviations from target level (1.2
      +/- 1.6 mg/dl). Operational time was as high as 95.4% +/- 4.1% (means +/- SD).
      CONCLUSIONS: The selected parameters seem to be adequate to characterize clamp
      quality. The novel, fully automated clamp device ClampArt achieves high clamp
      quality, which in future trials should be compared with other (automated and
      manual) clamp methods.

PMID- 25852076
TI  - Employment and disability pension after central nervous system infections in
      adults.
AB  - In this nationwide population-based cohort study using national Danish
      registries, in the period 1980-2008, our aim was to study employment and receipt
      of disability pension after central nervous system infections. All patients
      diagnosed between 20 and 55 years of age with meningococcal (n = 451),
      pneumococcal (n = 553), or viral (n = 1,433) meningitis or with herpes simplex
      encephalitis (n = 115), who were alive 1 year after diagnosis, were identified.
      Comparison cohorts were drawn from the general population, and their members were
      individually matched on age and sex to patients. Five years after diagnosis, the
      differences in probability of being employed as a former patient with
      pneumococcal meningitis or herpes simplex encephalitis versus being a member of
      the comparison cohorts were -19.9% (95% confidence interval (CI): -24.7, -15.1)
      and -21.1% (95% CI: -33.0, -9.3), respectively, and the corresponding differences
      in probability of receiving disability pension were 20.2% (95% CI: 13.7, 26.7)
      and 16.2% (95% CI: 6.2, 26.3). The differences in probability of being employed
      or receiving disability pension in former meningococcal or viral meningitis
      patients versus members of the comparison cohorts were small. In conclusion,
      pneumococcal meningitis and herpes simplex encephalitis were associated with
      substantially decreased employment and increased need for disability pension.
      These associations did not seem to apply to meningococcal meningitis or viral
      meningitis. 

PMID- 25852077
TI  - Obesity and Prostate Cancer Risk According to Tumor TMPRSS2:ERG Gene Fusion
      Status.
AB  - The T2E gene fusion, formed by fusion of the transmembrane protease, serine 2,
      gene (TMPRSS2) with the erythroblast transformation-specific (ETS)-related gene
      (ERG), is found in approximately 50% of prostate cancers and may characterize
      distinct molecular subtypes of prostate cancer with different etiologies. We
      investigated the relationship between body mass index (BMI; weight (kg)/height
      (m)(2)) and prostate cancer risk by T2E status. Study participants were residents
      of King County, Washington, recruited for 2 population-based case-control studies
      conducted in 1993-1996 and 2002-2005. Tumor T2E status was determined for 563
      prostate cancer patients who underwent radical prostatectomy. Information on
      weight, height, and covariables was obtained through in-person interviews. We
      performed polytomous logistic regression to calculate odds ratios and 95%
      confidence intervals for T2E-positive and -negative prostate cancer. Comparing
      the highest BMI quartile with the lowest, inverse associations were observed
      between recent (>=29.7 vs. <24.5: odds ratio = 0.66, 95% confidence interval:
      0.45, 0.97) and maximum (>=31.8 vs. <25.9: odds ratio = 0.69, 95% confidence
      interval: 0.47, 1.02) BMI and the risk of T2E-positive prostate cancer. No
      significant associations were seen for men with T2E-negative tumors. This study
      provides evidence that obesity is specifically associated with reduced risk of
      developing androgen-responsive T2E fusion-positive tumors. The altered steroid
      hormone profile in obese men may contribute to this inverse association. 

PMID- 25852078
TI  - Reconstructing Past Admixture Processes from Local Genomic Ancestry Using Wavelet
      Transformation.
AB  - Admixture between long-separated populations is a defining feature of the genomes
      of many species. The mosaic block structure of admixed genomes can provide
      information about past contact events, including the time and extent of
      admixture. Here, we describe an improved wavelet-based technique that better
      characterizes ancestry block structure from observed genomic patterns. principal
      components analysis is first applied to genomic data to identify the primary
      population structure, followed by wavelet decomposition to develop a new
      characterization of local ancestry information along the chromosomes. For testing
      purposes, this method is applied to human genome-wide genotype data from
      Indonesia, as well as virtual genetic data generated using genome-scale
      sequential coalescent simulations under a wide range of admixture scenarios. Time
      of admixture is inferred using an approximate Bayesian computation framework,
      providing robust estimates of both admixture times and their associated levels of
      uncertainty. Crucially, we demonstrate that this revised wavelet approach, which
      we have released as the R package adwave, provides improved statistical power
      over existing wavelet-based techniques and can be used to address a broad range
      of admixture questions. 

PMID- 25852079
TI  - Can Medical Diagnosis Benefit from "Unconscious Thought"?
AB  - The unconscious thought theory argues that making complex decisions after a
      period of distraction can lead to better decision quality than deciding either
      immediately or after conscious deliberation. Two studies have tested this
      unconscious thought effect (UTE) in clinical diagnosis with conflicting results.
      The studies used different methodologies and had methodological weaknesses. We
      attempted to replicate the UTE in medical diagnosis by providing favorable
      conditions for the effect while maintaining ecological validity. Family
      physicians (N= 116) diagnosed 3 complex cases in 1 of 3 thinking modes:
      immediate, unconscious (UT), and conscious (CT). Cases were divided into short
      sentences, which were presented briefly and sequentially on computer. After each
      case presentation, the immediate response group gave a diagnosis, the UT group
      performed a 2-back distraction task for 3 min before giving a diagnosis, and the
      CT group could take as long as necessary before giving a diagnosis. We found no
      differences in diagnostic accuracy between groups (P= 0.95). The CT group took a
      median of 7 s to diagnose, which suggests that physicians were able to diagnose
      "online," as information was being presented. The lack of a difference between
      the immediate and UT groups suggests that the distraction had no additional
      effect on performance. To assess the decisiveness of the evidence of this null
      result, we computed a Bayes factor (BF01) for the 2 comparisons of interest. We
      found a BF01of 5.76 for the UT versus immediate comparison and of 3.61 for the UT
      versus CT comparison. Both BFs provide substantial evidence in favor of the null
      hypothesis: physicians' diagnoses made after distraction are no better than
      diagnoses made either immediately or after self-paced deliberation.

PMID- 25852080
TI  - Empirical Treatment Effectiveness Models for Binary Outcomes.
AB  - Randomized trials provide strong evidence regarding efficacy of interventions but
      are limited in their capacity to address potential heterogeneity in effectiveness
      within broad clinical populations. For example, a treatment that on average is
      superior may be distinctly worse in certain patients. We propose a technique for
      using large electronic health registries to develop and validate decision models
      that measure-for distinct combinations of covariate values-the difference in
      predicted outcomes among 2 alternative treatments. We demonstrate the methodology
      in a prototype analysis of in-hospital mortality under alternative
      revascularization treatments. First, we developed prediction models for a binary
      outcome of interest for each treatment. Decision criteria were then defined based
      on the treatment-specific model predictions. Patients were then classified as
      receiving concordant or discordant care (in relation to the model
      recommendation), and the association between discordance and outcomes was
      evaluated. We then present alternative decision criteria and validation
      methodologies, as well as sensitivity analyses that investigate 1) the imbalance
      between treatments on observed covariates and 2) the aggregate impact of
      unobserved covariates. Our methodology supplements population-average clinical
      trial results by modeling heterogeneity in outcomes according to specific
      covariate values. It thus allows for assessment of current practice, from which
      cogent hypotheses for improved care can be derived. Newly emerging large
      population registries will allow for accurate predictions of outcome risk under
      competing treatments, as complex functions of predictor variables. Whether or not
      the models might be used to inform decision making depends on the extent to which
      important predictors are available. Further work is needed to understand the
      strengths and limitations of this approach, particularly in relation to those
      based on randomized trials.

PMID- 25852081
TI  - In vivo cardiac role of migfilin during experimental pressure overload.
AB  - AIMS: Increased myocardial wall strain triggers the cardiac hypertrophic response
      by increasing cardiomyocyte size, reprogramming gene expression, and enhancing
      contractile protein synthesis. The LIM protein, migfilin, is a cytoskeleton
      associated protein that was found to translocate in vitro into the nucleus in a
      Ca(2+)-dependent manner, where it co-activates the pivotal cardiac transcription
      factor Csx/Nkx2.5. However, the in vivo role of migfilin in cardiac function and
      stress response is unclear. METHODS AND RESULTS: To define the role of migfilin
      in cardiac hypertrophy, we induced hypertension by transverse aortic constriction
      (TAC) and compared cardiac morphology and function of migfilin knockout (KO) with
      wild-type (WT) hearts. Heart size and myocardial contractility were comparable in
      untreated migfilin KO and WT hearts, but migfilin-null hearts presented a reduced
      extent of hypertrophic remodelling in response to chronic hypertensile stress.
      Migfilin KO mice maintained their cardiac function for a longer time period
      compared with WT mice, which presented extensive fibrosis and death due to heart
      failure. Migfilin translocated into the nucleus of TAC-treated cardiomyocytes,
      and migfilin KO hearts showed reduced Akt activation during the early response to
      pressure overload. CONCLUSIONS: Our findings indicate an important role of
      migfilin in the regulation of cardiac hypertrophy upon experimental TAC.

PMID- 25852083
TI  - DNA-dependent protein kinase (DNA-PK) permits vascular smooth muscle cell
      proliferation through phosphorylation of the orphan nuclear receptor NOR1.
AB  - AIMS: Being central part of the DNA repair machinery, DNA-dependent protein
      kinase (DNA-PK) seems to be involved in other signalling processes, as well. NOR1
      is a member of the NR4A subfamily of nuclear receptors, which plays a central
      role in vascular smooth muscle cell (SMC) proliferation and in vascular
      proliferative processes. We determined putative phosphorylation sites of NDA-PK
      in NOR1 and hypothesized that the enzyme is able to modulate NOR1 signalling and,
      this way, proliferation of SMC. METHODS AND RESULTS: Cultured human aortic SMC
      were treated with the specific DNA-PK inhibitor NU7026 (or siRNA), which resulted
      in a 70% inhibition of FCS-induced proliferation as measured by BrdU
      incorporation. Furthermore, FCS-stimulated up-regulation of NOR1 protein as well
      as the cell-cycle promoting proteins proliferating cell nuclear antigen (PCNA),
      cyclin D1, and hyperphosphorylation of the retinoblastoma protein were prevented
      by DNA-PK inhibition. Co-immunoprecipitation studies from VSM cell lysates
      demonstrated that DNA-PK forms a complex with NOR1. Mutational analysis and
      kinase assays demonstrated that NOR1 is a substrate of DNA-PK and is
      phosphorylated in the N-terminal domain. Phosphorylation resulted in post
      transcriptional stabilization of the protein through prevention of its
      ubiquitination. Active DNA-PK and NOR1 were found predominantly expressed within
      the neointima of human atherosclerotic tissue specimens. In mice, inhibition of
      DNA-PK significantly attenuated neointimal lesion size 3 weeks after wire-injury.
      CONCLUSION: DNA-PK directly phosphorylates NOR-1 and, this way, modulates SMC
      proliferation. These data add to our understanding of vascular remodelling
      processes and opens new avenues for treatment of vascular proliferative diseases.

PMID- 25852082
TI  - A novel human R25C-phospholamban mutation is associated with super-inhibition of
      calcium cycling and ventricular arrhythmia.
AB  - AIMS: Depressed sarcoplasmic reticulum (SR) Ca(2+) cycling, a universal
      characteristic of human and experimental heart failure, may be associated with
      genetic alterations in key Ca(2+)-handling proteins. In this study, we identified
      a novel PLN mutation (R25C) in dilated cardiomyopathy (DCM) and investigated its
      functional significance in cardiomyocyte Ca(2+)-handling and contractility.
      METHODS AND RESULTS: Exome sequencing identified a C73T substitution in the
      coding region of PLN in a family with DCM. The four heterozygous family members
      had implantable cardiac defibrillators, and three developed prominent ventricular
      arrhythmias. Overexpression of R25C-PLN in adult rat cardiomyocytes significantly
      suppressed the Ca(2+) affinity of SR Ca(2+)-ATPase (SERCA2a), resulting in
      decreased SR Ca(2+) content, Ca(2+) transients, and impaired contractile
      function, compared with WT-PLN. These inhibitory effects were associated with
      enhanced interaction of R25C-PLN with SERCA2, which was prevented by PKA
      phosphorylation. Accordingly, isoproterenol stimulation relieved the depressive
      effects of R25C-PLN in cardiomyocytes. However, R25C-PLN also elicited increases
      in the frequency of Ca(2+) sparks and waves as well as stress-induced
      aftercontractions. This was accompanied by increased Ca(2+)/calmodulin-dependent
      protein kinase II activity and hyper-phosphorylation of RyR2 at serine 2814.
      CONCLUSION: The findings demonstrate that human R25C-PLN is associated with super
      inhibition of SERCA2a and Ca(2+) transport as well as increased SR Ca(2+) leak,
      promoting arrhythmogenesis under stress conditions. This is the first mechanistic
      evidence that increased PLN inhibition may impact both SR Ca(2+) uptake and
      Ca(2+) release activities and suggests that the human R25C-PLN may be a
      prognostic factor for increased ventricular arrhythmia risk in DCM carriers.

PMID- 25852084
TI  - Lymphatic vascular integrity is disrupted in type 2 diabetes due to impaired
      nitric oxide signalling.
AB  - AIMS: Lymphatic vessel dysfunction is an emerging component of metabolic diseases
      and can lead to tissue lipid accumulation, dyslipidaemia, and oedema. While lymph
      leakage has been implicated in obesity and hypercholesterolaemia, whether similar
      lymphatic dysfunction exists in diabetes has not been investigated. METHODS AND
      RESULTS: To measure the lymphatic integrity of transgenic mice, we developed a
      new assay that quantifies the solute permeability of murine collecting lymphatic
      vessels. Compared with age-matched wild-type (WT) controls, the permeability of
      collecting lymphatics from diabetic, leptin receptor-deficient (db/db) mice was
      elevated >130-fold. Augmenting nitric oxide (NO) production by suffusion of l
      arginine rescued this defect. Using pharmacological tools and eNOS(-/-) mice, we
      found that NO increased WT lymphatic permeability, but reduced db/db lymphatic
      permeability. These conflicting actions of NO were reconciled by the finding that
      phosphodiesterase 3 (PDE3), normally inhibited by NO signalling, was active in
      db/db lymphatics and inhibition of this enzyme restored barrier function.
      CONCLUSION: In conclusion, we identified the first lymphatic vascular defect in
      type 2 diabetes, an enhanced permeability caused by low NO bioavailability.
      Further, this demonstrates that PDE3 inhibition is required to maintain lymphatic
      vessel integrity and represents a viable therapeutic target for lymphatic
      endothelial dysfunction in metabolic disease.

PMID- 25852086
TI  - UK death rates in children's heart surgery have almost halved over past decade.

PMID- 25852085
TI  - Inhibition of type 5 phosphodiesterase counteracts beta2-adrenergic signalling in
      beating cardiomyocytes.
AB  - AIMS: Compartmentalization of cAMP and PKA activity in cardiac muscle cells plays
      a key role in maintaining basal and enhanced contractility stimulated by
      sympathetic nerve activity. In cardiomyocytes, activation of adrenergic receptor
      increases cAMP production, which is countered by the hydrolytic activity of
      selective phosphodiesterases (PDEs). The intracellular regional dynamics of cAMP
      production and hydrolysis modulate downstream signals resulting in different
      biological responses. The interplay between beta receptors (betaARs) signalling
      and phosphodiesterase 5 (PDE5) activity remains to be addressed. METHODS AND
      RESULTS: Using combined strategies with pharmacological inhibitors and genetic
      deletion of PDEs and betaAR isoforms, we revealed a specific pool of cAMP that is
      under dual regulation by PDE2 and, indirectly, PDE5 activity. Inhibition of PDE5
      with sildenafil produces a cGMP-dependent activation of PDE2 that attenuates cAMP
      generation induced by betaAR agonists, with concomitant modulation of stimulated
      contraction rate and calcium transients. PDE2 haploinsufficiency abolished the
      effects of sildenafil. The negative chronotropic effect of PDE5 inhibition
      through PDE2 activation was also observed in sinoatrial node tissue from adult
      mice. PDE5 inhibition selectively lowered contraction rate stimulated by beta2AR,
      but not beta1AR activation, supporting a compartmentalization of the cGMP
      modulated pool of cAMP. CONCLUSION: These data identify a new effect of PDE5
      inhibitors on the modulation of cardiomyocyte response to adrenergic stimulation
      via PDE5-PDE2-mediated cross-talk.

PMID- 25852087
TI  - Drought-induced tree mortality: from discrete observations to comprehensive
      research.

PMID- 25852088
TI  - Is nitrous oxide a genotoxic carcinogen?
AB  - Nitrous oxide (N2O) has been widely used as a dental and surgical anaesthetic for
      over 150 years. However, results from a recent study suggested that increased DNA
      damage was seen in lymphocytes from surgical patients and this led to its
      continued clinical use to be questioned. The data can be challenged on technical
      grounds and must be considered with other studies in order to assess any possible
      risk. There are other studies indicating that N2O has weak genotoxicity in man,
      but these are confused by exposure of the populations to other anaesthetic gases
      including isoflurane and sevoflurane, both of which have also been reported to
      increase DNA damage. It should be noted that the suggested genotoxic mechanisms
      are all indirect, including folate deficiency, oxidative stress and homocysteine
      toxicity. Further, results from in vitro studies indicate that N2O has no direct
      DNA reactivity as negative results were obtained in a bacterial mutation (Ames)
      test and an assay for mutation at the hprt locus in Chinese hamster lung cells.
      Although not performed to definitive study designs, no evidence of
      carcinogenicity was seen in two long-term tests in mice and another in rats.
      Although there is some evidence that N2O is weakly genotoxic in humans, this
      appears to be similar to that reported for isoflurane and sevoflurane and all the
      postulated mechanisms have clear thresholds with no evidence of direct DNA
      reactivity. Because any potential genotoxic mechanism would have a threshold, it
      seems reasonable to conclude that neither occasional high exposure to patients as
      an anaesthetic nor low-level exposure to staff within published recommended
      exposure limits presents any significant carcinogenic risk. 

PMID- 25852089
TI  - Pityriasis versicolor.

PMID- 25852090
TI  - CCR4+ Regulatory T Cells Accumulate in the Very Elderly and Correlate With
      Superior 8-Year Survival.
AB  - CD4(+) regulatory T cells (Tregs) are a distinct population of T cells involved
      in maintaining peripheral tolerance to self-antigens. Several studies have shown
      increased frequency and number of Tregs in the elderly. Whether such an increase
      has any clinical relevance has not been addressed. Here, we have analyzed
      circulating Tregs in 114 donors between the ages of 18 and 89 years and assessed
      their implications for survival of the very elderly. In line with previously
      published data, we observed higher proportions of Tregs in the elderly.
      Expression of chemokine receptor 4 (CCR4) by Tregs has been shown to characterize
      antigen-primed activated Tregs with immediate suppressive function. Thus we
      further analyzed Tregs expressing or lacking this chemokine receptor. There were
      more CCR4(+) and CCR4(-) Tregs in the elderly than the young. Finally, using a
      subset of 48 elderly donors participating in the Leiden 85-plus study we
      documented that people with greater median frequencies of CCR4(+) Tregs enjoyed a
      better 8-year survival rate than those with lower frequencies of these cells. Our
      data, demonstrating for the first time a positive correlation between increased
      frequency of Tregs and survival in the elderly, imply an increasing importance of
      controlling inappropriate immune responses and inflammation as we grew old.

PMID- 25852091
TI  - Cancer in a gerontological context.

PMID- 25852092
TI  - Prevalence of abuse in mentally ill patients visiting outpatient setting in a
      tertiary care hospital in India.
AB  - AIM: In a developing country such as India, the abuse of patients suffering from
      psychiatric disorders has been underreported. The aim of this study was to detect
      abuse in chronically ill psychiatric patients visiting a psychiatric outpatient
      setting in a tertiary care hospital in Delhi, India. MATERIAL AND METHODS: A
      cross-sectional descriptive written survey was carried out on 406 patients. A
      self-administered questionnaire for patient abuse was developed in Hindi based on
      the World Health Organization's Domestic Violence Questionnaire that encompassed
      questions regarding physical, emotional and sexual abuse. RESULTS: Of the 406
      patients, 294 (72%) suffered from abuse, with 64% experiencing emotional abuse,
      39% physical abuse and 21% sexual abuse. In chronically ill psychiatric patients,
      a significant association was found between education and abuse, with most abuse
      occurring among senior secondary pass outs (i.e. 11-12 years of education) and
      least among junior high school pass outs (6-8 years of education). A majority
      (74%) of these patients lived in urban areas (p = .020). A significant
      association was also found between abuse and the psychiatric diagnosis of the
      patient, with 53% suffering from depression, 66% anxiety disorder, 81% bipolar
      disorder, 94% psychotic disorder, 86% obsessive compulsive disorder, 44% sexual
      disorder and 12% other psychiatric disorders. CONCLUSIONS: There is a need to
      create awareness in society in order to prevent abuse. Screening for abuse in
      routine psychiatric practice is of utmost importance so that timely interventions
      can be given, thereby preventing its deleterious health consequences.

PMID- 25852093
TI  - Benefit of STR-based chimerism analysis to identify TA-GVHD as a cause of death:
      Utility of various biological specimens.
AB  - Transfusion-associated graft-versus-host disease (TA-GVHD) is a rare condition.
      It can occur after blood transfusion in immune-compromised and occasionally even
      in immune-competent patients, and is associated with a mortality rate of >90%.
      The diagnosis of TA-GVHD is often delayed because of its non-specific clinical
      features. A case of an immune-competent child who developed TA-GVHD is reported
      here. DNA profiling (short tandem repeat analysis), a technique that has a wide
      application in forensic medicine, was performed to detect the presence of donor
      cells in this patient. The findings suggest that more studies are needed with
      this tool, and the diagnostic potential of using other multiple biological
      specimens for DNA profiling such as the hair follicle and buccal swab should be
      evaluated. This is the first case report where the donor's DNA fingerprinting
      pattern was substantiated from a patient's hair follicle sample. Chimerism was
      also present in the blood and buccal swab specimens. 

PMID- 25852094
TI  - Health Research Symposium 2014: translating health research into policy for
      health of the population.

PMID- 25852095
TI  - Stigma towards people with psychiatric disorders.

PMID- 25852096
TI  - Epidemiology and natural history of depressive disorders in primary care.

PMID- 25852097
TI  - Early intervention versus standard care for psychosis in Hong Kong: a 10-year
      study.

PMID- 25852098
TI  - Three-year community case management for early psychosis: a randomised controlled
      study.

PMID- 25852099
TI  - Perceived stigmatisation of patients with mental illness and its psychosocial
      correlates: a prospective cohort study.

PMID- 25852100
TI  - Health outcomes, community resources for health, and support strategies 12 months
      after discharge in patients with severe mental illness.

PMID- 25852101
TI  - Assertive community treatment for psychiatric patients with frequent
      hospitalisation.

PMID- 25852102
TI  - Pathway of psychiatric care in Hong Kong.

PMID- 25852103
TI  - Use of the Historical, Clinical, Risk Management-20 to assess the risk of
      violence by discharged psychiatric patients.

PMID- 25852105
TI  - A curious case of facial swelling in the night-time.

PMID- 25852104
TI  - RBM7 subunit of the NEXT complex binds U-rich sequences and targets 3'-end
      extended forms of snRNAs.
AB  - The Nuclear Exosome Targeting (NEXT) complex is a key cofactor of the mammalian
      nuclear exosome in the removal of Promoter Upstream Transcripts (PROMPTs) and
      potentially aberrant forms of other noncoding RNAs, such as snRNAs. NEXT is
      composed of three subunits SKIV2L2, ZCCHC8 and RBM7. We have recently identified
      the NEXT complex in our screen for oligo(U) RNA-binding factors. Here, we
      demonstrate that NEXT displays preference for U-rich pyrimidine sequences and
      this RNA binding is mediated by the RNA recognition motif (RRM) of the RBM7
      subunit. We solved the structure of RBM7 RRM and identified two phenylalanine
      residues that are critical for interaction with RNA. Furthermore, we showed that
      these residues are required for the NEXT interaction with snRNAs in vivo.
      Finally, we show that depletion of components of the NEXT complex alone or
      together with exosome nucleases resulted in the accumulation of mature as well as
      extended forms of snRNAs. Thus, our data suggest a new scenario in which the NEXT
      complex is involved in the surveillance of snRNAs and/or biogenesis of snRNPs. 

PMID- 25852106
TI  - Stress and Negative Relationship Quality among Older Couples: Implications for
      Blood Pressure.
AB  - OBJECTIVES: The cardiovascular system may represent a significant pathway by
      which marriage and stress influence health, but research has focused on married
      individuals cross-sectionally. This study examined associations among chronic
      stress, negative spousal relationship quality, and systolic blood pressure over
      time among middle-aged and older husbands and wives. METHOD: Participants were
      from the nationally representative longitudinal Health and Retirement Study. A
      total of 1,356 (N = 2,712) married and cohabitating couples completed
      psychosocial and biomeasure assessments in waves 2006 and 2010. Analyses examined
      whether Wave 1 (2006) relationship quality and stress were associated with
      changes in blood pressure over time. RESULTS: The effects of stress and negative
      relationship quality were dyadic and varied by gender. Husbands had increased
      blood pressure when wives reported greater stress, and this link was exacerbated
      by negative spousal relationship quality. Negative relationship quality predicted
      increased blood pressure when both members of the couple reported negative
      quality relations. DISCUSSION: Findings support the dyadic biopsychosocial model
      of marriage and health indicating: (a) stress and relationship quality directly
      effect the cardiovascular system, (b) relationship quality moderates the effect
      of stress, and (c) the dyad rather than only the individual should be considered
      when examining marriage and health.

PMID- 25852107
TI  - Paradoxical effect of capecitabine in 5-fluorouracil-induced cardiotoxicity: A
      case vignette and literature review.
AB  - 5-fluorouracil is a chemotherapeutic agent that plays an important role in the
      treatment of various cancers including head and neck and gastrointestinal
      malignancies. Therapy with 5-fluorouracil is rarely associated with cardiotoxic
      effects including angina, heart failure, myocardial infarction and cardiac
      arrest, resulting in discontinuation at the expense of sub-optimal treatment of
      the targeted malignancy. In this article, we review the literature reported on 5
      fluorouracil-associated cardiotoxicity and present a case of a patient who
      experienced chest pain on 5-fluorouracil. The cardiac symptoms subsided after
      initiation of capecitabine, the oral formulation of 5-fluorouracil. To our
      knowledge, this is only the second reported case where 5-fluorouracil was
      successfully replaced by capecitabine without recurrence of cardiac symptoms.
      Capecitabine may be a viable option for patients who develop 5-fluorouracil
      induced chest pain. However, large clinical trials are warranted to confirm these
      findings. Currently, there is insufficient evidence to recommend an optimal
      approach for safe and effective alternative treatment for patients who experience
      5-fluorouracil-induced cardiac adverse events. 

PMID- 25852108
TI  - Ultrasound for internists: changing bedside examination.

PMID- 25852109
TI  - Lung ultrasound: routine practice for the next generation of internists.
AB  - BACKGROUND: The lung is at the crossroads of ventilation and circulation and can
      provide a wealth of diagnostic information. In the past, lung ultrasound (LUS)
      was considered impossible. However, the interplay between air, fluid and pleurae
      creates distinctive artefacts. Combinations of these artefacts can help
      differentiate between various pathological processes, including pulmonary oedema,
      pneumonia, pulmonary embolism, obstructive airway disease and pneumothorax. LUS,
      when used by experienced physicians, is superior to chest X-ray and comparable to
      computed tomography for establishing a diagnosis in acutely dyspnoeic patients.
      LUS allows for rapid, non-invasive and bedside patient assessment. It is
      therefore unfortunate that unlike many other medical specialists in the
      Netherlands, internists have not yet incorporated LUS into their daily practice.
      OBJECTIVES: This review aims to be the starting point for internists wanting to
      acquire competence in LUS. REVIEW CONTENT: This narrative review describes the
      principles of ultrasound equipment, LUS artefacts, gives practical guidance to
      perform LUS and provides a road map towards LUS competence. Furthermore, it
      presents a decision tree to differentiate between causes of acute dyspnoea.
      AUTHORS CONCLUSIONS: LUS is a promising diagnostic technique that can be of great
      help for the internist. It can be applied directly at the bedside and can also be
      used to follow up on disease progression and therapy. It is our belief that it
      will replace the stethoscope and that it will be the most used imaging technique
      in the near future, especially in dyspnoeic patients.

PMID- 25852110
TI  - Hepcidin in chronic kidney disease: not an anaemia management tool, but promising
      as a cardiovascular biomarker.
AB  - Hepcidin is a key regulator of iron homeostasis and plays a role in the
      pathogenesis of anaemia of chronic disease. Its levels are increased in patients
      with chronic kidney disease (CKD) due to diminished renal clearance and an
      inflammatory state. Increased hepcidin levels in CKD patients are supposed to be
      responsible for functional iron deficiency in these patients and contribute to
      renal anaemia and resistance to erythropoiesis-stimulating agents. Therefore,
      hepcidin was purported to be useful as a management tool guiding treatment of
      renal anaemia. Furthermore, since hepcidin is associated with iron accumulation
      in macrophages in the vessel wall inducing oxidative stress and atherosclerosis,
      it has been speculated that hepcidin might function as a biomarker of
      cardiovascular disease. In this descriptive review, the merits of hepcidin with
      respect to its role in the pathophysiology of renal anaemia in CKD patients, its
      presumptive role as a practical diagnostic tool guiding management of renal
      anaemia, and its possible usefulness as a prognostic biomarker will be discussed.

PMID- 25852111
TI  - The standardised mortality ratio: the proper quality indicator in acute
      leukaemia?
AB  - BACKGROUND: The standardised mortality ratio (SMR) is a quality indicator used to
      measure quality of care in the Netherlands. It is subject to much criticism,
      which was the reason to study the value of the SMR as a quality indicator for the
      treatment of acute leukaemia. METHODS: A retrospective analysis was performed in
      patients with acute leukaemia admitted to a Santeon hospital during the period
      2005-2009. SMR values were calculated and compared with the overall survival
      (OS). RESULTS: During the study period, 455 unique patients were admitted with
      acute leukaemia. SMR calculation was based on 992 admissions. SMR analysis
      yielded a high mortality ratio in hospital 1, 2, 3 and 4 in comparison with the
      national average (100), significant for hospital 1 and 4 (180 [CI 95% 126-257]
      and 187 [CI 95% 134-261], respectively) OS analysis also showed a significantly
      different outcome between hospitals. However, using OS as outcome parameter,
      hospital 2 and 6 showed the lowest performance as compared with hospital 1 and 4
      using SMR as parameter. After multivariate analysis, age (HR 1.04; CI 95% 1.03
      1.05; p < 0.001) and hospital (hospital 5 compared with 6: HR 0.54; CI 95% 0.30-
      .98; p = 0.043; hospital 2 compared with 1: HR 1.51; CI 95% 1.02-2.23; p = 0.039)
      were the only significant variables that influenced OS. CONCLUSION: Outcome
      according to SMR is not equivalent to outcome according to OS. This study shows
      that the use of the SMR as a quality indicator for the treatment of acute
      leukaemia does not appear to be justified.

PMID- 25852112
TI  - Prevalence and correction of severe hypovitaminosis D in patients over 50 years
      with a low-energy fracture.
AB  - PURPOSE/INTRODUCTION: To examine the increase in serum 25(OH) vitamin D levels
      after supplementation with 800 IU/day of vitamin D in patients with low vitamin D
      levels and which factors affected the increase in vitamin D levels. METHODS: The
      study included patients > 50 years with a low-energy fracture and a vitamin D
      level < 30 nmol/l. This was a retrospective study and was carried out at a large
      non-teaching hospital in the Netherlands. RESULTS: 82 patients were included,
      mean basal 25(OH) vitamin D level was 21.2 nmol/l. After a mean of 9.8 weeks, the
      mean increase in vitamin D was 48.5 nmol/l. Only 45.1% reached the target level
      of > 50 nmol/l. The increase was correlated with the basal level of vitamin D (p
      < 0.05), and the time interval between the two vitamin D measurements (p < 0.05)
      and was inversely related to body weight (p < 0.05), but was not related to age,
      gender or renal function. CONCLUSIONS: We found that the generally recommended
      dosage of 800 IU of vitamin D per day resulted in suboptimal serum levels after
      ten weeks of treatment in more than half of the patients. The increase in vitamin
      D levels was higher in patients with low body weight and in patients with very
      low basal vitamin D levels. These data suggest that these patients should
      initially be treated with higher dosages of vitamin D. If not possible, vitamin D
      measurements should be performed after at least six months of supplementation
      with dosage adjustment.

PMID- 25852113
TI  - Hypercholesterolaemia and hepatosplenomegaly: two manifestations of cholesteryl
      ester storage disease.
AB  - Cholesteryl ester storage disease (CESD) is a rare autosomal recessive disease
      caused by mutations in LIPA. Here we describe two different clinical
      presentations of this disease: one case with a clear phenotype of familial
      hypercholesterolaemia and one case with hepatosplenomegaly from childhood
      onwards. These two cases exemplify the diversity of clinical phenotypes of
      patients with CESD. Knowledge on the phenotypic variability of the disease is of
      clinical relevance in light of enzyme replacement therapy (sebelipase alpha) for
      patients with mutations in LIPA, which is currently under development. 

PMID- 25852114
TI  - Life-threatening acute lung injury after gamma butyrolactone ingestion.
AB  - We describe a case of a 44-year-old woman with a borderline personality disorder
      and chronic gamma- butyrolactone (GBL) use who presented with progressive
      dyspnoea and an altered mental status. A high anion gap metabolic acidosis and
      acute lung injury was diagnosed. We hypothesise this was caused by GBL. In this
      case report we describe the diagnostic process and possible pathophysiological
      mechanisms that may have led to this life-threatening condition. 

PMID- 25852115
TI  - Ticagrelor-induced renal failure leading to statin-induced rhabdomyolysis.
AB  - Renal function deterioration is a rather frequent side effect of ticagrelor; this
      is especially so in patients over the age of 75, with pre-existent mild renal
      failure and/or taking an angiotensin receptor inhibitor. We describe a patient in
      whom deterioration of renal function due to ticagrelor led to a rise in serum
      concentration of rosuvastatin which resulted in rhabdomyolysis. The presented
      case emphasises the importance to check renal function routinely before and one
      month after starting ticagrelor and to screen carefully for possible interactions
      with other drugs.

PMID- 25852116
TI  - An immunocompromised woman with a lung tumour.

PMID- 25852117
TI  - Intermittent abdominal pain and melaena in a 64-year-old man.

PMID- 25852118
TI  - Should we put pressure on using lower levels of PEEP in patients without ARDS in
      The Netherlands?

PMID- 25852119
TI  - Investigation that may have contributed to GP's suicide was carried out
      correctly, report says.

PMID- 25852120
TI  - Quantitative Assessment of Multiorgan Sequestration of Parasites in Fatal
      Pediatric Cerebral Malaria.
AB  - Children in sub-Saharan Africa continue to acquire and die from cerebral malaria,
      despite efforts to control or eliminate the causative agent, Plasmodium
      falciparum. We present a quantitative histopathological assessment of the
      sequestration of parasitized erythrocytes in multiple organs obtained during a
      prospective series of 103 autopsies performed between 1996 and 2010 in Blantyre,
      Malawi, on pediatric patients who died from cerebral malaria and controls. After
      the brain, sequestration of parasites was most intense in the gastrointestinal
      tract, both in patients with cerebral malaria and those with parasitemia in other
      organs. Within cases of histologically defined cerebral malaria, which includes
      phenotypes termed "sequestration only" (CM1) and "sequestration with
      extravascular pathology" (CM2), CM1 was associated with large parasite numbers in
      the spleen and CM2 with intense parasite sequestration in the skin. A striking
      histological finding overall was the marked sequestration of parasitized
      erythrocytes across most organs in patients with fatal cerebral malaria,
      supporting the hypothesis that the disease is, in part, a result of a high level
      of total-body parasite sequestration. 

PMID- 25852121
TI  - Des agents de sante communautaires pour la promotion de la sante des pasteurs
      nomades au Mali.
AB  - Au Mali, les nomades (des Maures, Touaregs et Peulhs) representent environ 1,25
      million de personnes. Les services de sante leur sont peu accessibles en raison
      de leur mobilite, liee a leur activite d'elevage. La question que se posent
      plusieurs intervenants en sante publique des pays ou vivent ces nomades est de
      savoir comment ameliorer leur sante. Dans ce commentaire, apres un bref expose
      des problemes lies a l'acces aux services de sante, nous proposons une approche
      innovante et holistique de la sante, qui soutient que des agents de sante
      communautaires (ASC) pourraient contribuer a ameliorer la sante des nomades en
      offrant conjointement des services de sante aux nomades et a leurs animaux (le
      concept " One Health " [d'Une Seule Sante]). Des pistes de reflexion sont
      degagees, quant aux principaux defis pour leur efficacite et durabilite, qui sont
      la conception et gestion du programme, leur soutien par les communautes et leur
      integration aux services de sante publique et veterinaire.

PMID- 25852123
TI  - Editorial commentary: what constitutes appropriate treatment of post-Lyme disease
      symptoms and other pain and fatigue syndromes?

PMID- 25852124
TI  - Unorthodox alternative therapies marketed to treat Lyme disease.
AB  - BACKGROUND: Some patients with medically unexplained symptoms or alternative
      medical diagnoses suspect that they chronically suffer from the tick-borne
      infection Lyme disease. These patients are commonly targeted by providers of
      alternative therapies. This study was designed to identify and characterize the
      range of unorthodox alternative therapies advertised to patients with a diagnosis
      of Lyme disease. METHODS: Internet searches using the Google search engine were
      performed to identify the websites of clinics and services that marketed
      nonantimicrobial therapies for Lyme disease. We subsequently used the PubMed
      search engine to identify any scientific studies evaluating such treatments for
      Lyme disease. Websites were included in our review so long as they advertised a
      commercial, nonantimicrobial product or service that specifically mentioned
      utility for Lyme disease. Websites with patient testimonials (such as discussion
      groups) were excluded unless the testimonial appeared as marketing on a
      commercial site. RESULTS: More than 30 alternative treatments were identified,
      which fell into several broad categories: these included oxygen and reactive
      oxygen therapy; energy and radiation-based therapies; nutritional therapy;
      chelation and heavy metal therapy; and biological and pharmacological therapies
      ranging from certain medications without recognized therapeutic effects on
      Borrelia burgdorgeri to stem cell transplantation. Review of the medical
      literature did not substantiate efficacy or, in most cases, any rationale for the
      advertised treatments. CONCLUSIONS: Providers of alternative therapies commonly
      target patients who believe they have Lyme disease. The efficacy of these
      unconventional treatments for Lyme disease is not supported by scientific
      evidence, and in many cases they are potentially harmful.

PMID- 25852125
TI  - Low risk of lamivudine-resistant HBV and hepatic flares in treated HIV-HBV
      coinfected patients from Cote d'Ivoire.
AB  - BACKGROUND: In HIV-HBV-coinfected patients from sub-Saharan Africa, incidence of
      antiviral resistant HBV-mutations after initiating long-term antiretroviral
      therapy (ART) has only been evaluated in limited patient populations. METHODS: In
      this nested, prospective cohort study from two randomized controlled trials in
      Cote d'Ivoire, 168 ART-naive HIV-HBV-coinfected patients, starting lamivudine
      (LAM, n=82) or tenofovir/emtricitabine (TDF/FTC, n=86) containing ART were
      included. HBV DNA viral load (VL) was quantified using an in-house assay
      (detection limit: <12 copies/ml) while pol and preS/S regions of positive samples
      were sequenced. RESULTS: At ART-initiation, 39 (23.2%) were hepatitis B e antigen
      positive, 53 (31.5%) had alanine or aspartate aminotransferase levels >40 IU/ml
      and 98/100 (98.0%) harboured genotype E. Among the 127 (75.6%) patients with
      detectable baseline HBV VL (median 4.27 log10 copies/ml, IQR 3.14-7.64),
      cumulative percentage achieving undetectable HBV DNA was 74.2% for patients
      undergoing LAM-containing ART and 94.2% for TDF/FTC-containing ART after a median
      35.5 months (IQR 24.3-36.5). No baseline antiviral resistance mutations were
      observed. Among 28/127 (22.1%) patients with low-level persistent viraemia (last
      HBV VL: between 12 to <10(5) copies/ml), no incident amino acid changes
      associated with antiviral resistance were observed. Among 11/127 (8.7%) patients
      with high-level persistent viraemia (last HBV VL: >=10(5) copies/ml), only two
      harboured incident LAM-resistance mutations at positions rtV173L+rtL180M+rtM204V
      with no patient exhibiting TDF/FTC-resistance. Two patients had transaminase
      flares >120 IU/ml (incidence rate =0.5/100 person-years). CONCLUSIONS: Antiviral
      resistance, particularly to LAM, was remarkably rare in this cohort of HIV-HBV
      coinfected patients. Further research is needed to determine which coinfected
      populations might benefit from LAM-containing ART with low risk of resistance.

PMID- 25852127
TI  - Lipoprotein (a) upregulates ABCA1 in liver cells via scavenger receptor-B1
      through its oxidized phospholipids.
AB  - Elevated levels of lipoprotein (a) [Lp(a)] are a well-established risk factor for
      developing CVD. While Lp(a) levels are thought to be independent of other plasma
      lipoproteins, some trials have reported a positive association between Lp(a) and
      HDL. Whether Lp(a) has a direct effect on HDL is not known. Here we investigated
      to determine whether Lp(a) had any effect on the ABCA1 pathway of HDL production
      in liver cells. Incubation of HepG2 cells with Lp(a) upregulated the PPARgamma
      protein by 1.7-fold and the liver X receptor alpha protein by 3-fold. This was
      accompanied by a 1.8-fold increase in ABCA1 protein and a 1.5-fold increase in
      cholesterol efflux onto apoA1. We showed that Lp(a) was internalized by HepG2
      cells, however, the ABCA1 response to Lp(a) was mediated by the selective uptake
      of oxidized phospholipids (oxPLs) from Lp(a) via the scavenger receptor-B1 and
      not by Lp(a) internalization per se. We conclude that there is a biological
      connection between Lp(a) and HDL through the ability of Lp(a)'s oxPLs to
      upregulate HDL biosynthesis. 

PMID- 25852128
TI  - Environmental Risk Factors for Developing Catheter-Related Bloodstream Infection
      in Home Parenteral Nutrition Patients: A 6-Year Follow-up Study.
AB  - BACKGROUND: Tunneled, cuffed, central venous catheters, including Hickman
      catheters and peripherally inserted central venous catheters (PICCs), are the
      most commonly used venous access for home parenteral nutrition (HPN) therapy.
      Catheter-related bloodstream infection is the most prevalent and severe
      complication. This study investigated whether environmental risk factors,
      including smoking, catheter management by a home care nurse, colectomy with
      stoma, number of infusion days per week, and C-reactive protein at catheter
      insertion day, influenced the time to first catheter-related bloodstream
      infection (CRBSI). MATERIALS AND METHODS: In this 6-year (2008-2014)
      observational cohort study, adult patients with intestinal failure receiving HPN
      through either Hickman catheters or PICCs were included. Data were obtained by
      reviewing medical records, and the environmental risk factors were analyzed with
      the Cox proportional hazards model. RESULTS: A total of 295 catheters (Hickman
      catheters: n = 169 and PICCs: n = 126) inserted into 136 patients were
      registered. Using the PICCs, 1 additional infusion day per week showed to
      significantly decrease the time to first CRBSI by a factor of 2.47. Hickman
      catheters managed by a home care nurse had a significantly increased mean (SD)
      incidence of CRBSI of 1.45 (0.68) per 1000 catheter days. Hickman catheters not
      managed by a home care nurse had a mean (SD) incidence of 0.56 (0.24).
      CONCLUSION: Using the PICC, 1 additional infusion day per week decreased the time
      to first CRBSI, while having the Hickman catheter managed by a home care nurse
      increased the mean CRBSI incidence. No other risk factors were found.

PMID- 25852130
TI  - Evidence for iron deficiency screening "inadequate," US panel concludes.

PMID- 25852129
TI  - Effect of left ventricular ejection fraction on postoperative outcome in patients
      with severe aortic stenosis undergoing aortic valve replacement.
AB  - BACKGROUND: In asymptomatic patients with severe aortic stenosis, guidelines
      recommend left ventricular ejection fraction (LVEF) of <50% as the threshold for
      referral for aortic valve replacement. We investigated the importance of LVEF on
      long-term outcome after aortic valve replacement in symptomatic and asymptomatic
      patients with severe aortic stenosis. METHODS AND RESULTS: We retrospectively
      identified 2017 patients with severe aortic stenosis (aortic valve area<1 cm(2),
      mean gradient>=40 mm Hg, or indexed aortic valve area<0.6 cm(2)/m(2)) who
      underwent surgical aortic valve replacement from January 1995 to June 2009.
      Patients were divided into 4 groups depending on preoperative LVEF (<50% in 300
      [15%] patients, 50%-59% in 331 [17%], 60%-69% in 908 [45%], and >=70% in 478
      [24%]). During follow-up of 5.3+/-4.4 years, 1056 (52%) patients died. A decrease
      in mortality was observed with increasing LVEF, P<0.0001; 5-year mortality
      estimates (95% confidence interval) were 0.41 (0.35-0.47), LVEF<50%; 0.35 (0.29
      0.41), LVEF 50% to 59%; 0.26 (0.23-0.29), LVEF 60% to 69%; and 0.22 (0.18-0.26),
      LVEF>=70%. Compared with patients with LVEF>=60%, patients with LVEF 50% to 59%
      had increased mortality (hazard ratio [HR], 1.58; P<0.001), with similar risk
      increase in both symptomatic (HR, 1.56; P<0.001) and asymptomatic patients (HR,
      1.58; P=0.006). Correcting for risk factors, LV mass index, aortic valve area,
      and stroke volume index, LVEF was independently predictive of mortality (HR, 0.88
      per 10%; P<0.001). When this analysis was repeated in the subset of 1333 patients
      without history of coronary artery disease, LVEF remained associated with
      mortality (HR, 0.90 per 10%; P=0.009). CONCLUSIONS: LVEF is a powerful predictor
      of outcome in patients with severe aortic stenosis undergoing aortic valve
      replacement, independent of the presence of valve-related symptoms.

PMID- 25852132
TI  - The pilot, depression, and the salacious headlines that feed stigma.

PMID- 25852131
TI  - Potential role of electrostimulation in augmentation of venous blood flow after
      total knee replacement: A pilot study.
AB  - AIM: To investigate the potential role of a novel electrostimulation device in
      augmenting the femoral vein venous blood flow following total knee replacement
      surgery. MATERIAL AND METHODS: A total of 30 consecutive patients undergoing
      total knee replacement were allocated to receive either peroneal nerve
      electrostimulation plus low molecular weight heparin and below-knee compression
      stockings (Group 1, electrostimulation group, n = 15, mean age: 63.40 +/- 5.91
      years, male: female ratio 9:6) or low molecular weight heparin and below-knee
      compression stockings alone (Group 2, control group, n = 15, mean age: 63.86 +/-
      7.47 years, male: female ratio 8:7). Electrostimulation was performed for 1 h in
      every 4 h after the operation. Peak blood velocity in the femoral vein was
      evaluated with Duplex ultrasonongraphy in supine position. Presence of leg edema
      and calf diameter was also taken into consideration as outcome measures, which
      were recorded both before surgery and at the time of discharge from hospital.
      RESULTS: Postoperative peak blood flow velocity in the femoral vein was
      significantly higher in electrostimulation group compared to control group (17.46
      +/- 2.86 cm/s vs. 13.84 +/- 3.58 cm/s, p < 0.02). Electrostimulation group
      achieved a significant increase in peak blood flow velocity in the femoral vein
      after the operation (mean increase 67.48 +/- 17.38%, p < 0.001). CONCLUSION:
      Electrostimulation of the common peroneal nerve enhanced venous flow in the lower
      limb and may potentially be of use as a supplementary technique in deep venous
      prophylaxis following lower limb orthopedic operations.

PMID- 25852133
TI  - Cardiovascular effects of dipeptidyl peptidase-4 inhibitors in patients with type
      2 diabetes.
AB  - Cardiovascular (CV) disease is the leading cause of mortality and morbidity in
      patients with type 2 diabetes mellitus (T2DM). However, improving glycaemic
      control alone has not decreased CV events. Therapies that improve glycaemic
      control, CV disease risk factors and CV function are more likely to be
      successful. Dipeptidyl peptidase-4 (DPP-4) inhibitors prevent breakdown of
      incretin hormones glucagon-like peptide-1(GLP-1) and glucose-dependent
      insulinotropic peptide and improve glycaemic control in patients with T2DM. DPP-4
      acts on other substrates, many associated with cardioprotection. Thus, inhibition
      of DPP-4 may lead to elevations in these potentially beneficial substrates. Data
      from animal studies and small observational studies in humans suggest that DPP-4
      inhibitors may potentially reduce CV risk. However, recently completed CV outcome
      trials in patients with T2DM and CV disease or at high risk of adverse CV events
      have shown that the DPP-4 inhibitors saxagliptin and alogliptin neither increased
      nor decreased major adverse CV events. 

PMID- 25852134
TI  - Effect of heating rate on highly heat-resistant spore-forming microorganisms.
AB  - Highly heat-resistant spore-forming Bacillus cause nonsterility problems in
      canned food and reduce the shelf life of many processed foods. The aim of this
      research was to evaluate the thermal inactivation of Bacillus sporothermodurans
      IIC65, Bacillus subtilis IC9, and Geobacillus stearothermophilus T26 under
      isothermal and nonisothermal conditions. The data obtained showed that B.
      sporothermodurans and B. subtilis were more heat resistant than G.
      stearothermophilus. The survival curves of B. sporothermodurans and B. subtilis
      showed shoulders, while the survival curves of G. stearothermophilus showed
      tails. Under nonisothermal treatment, at heating rates of 1 and 20 C/min, time
      needed to completely inactivate G. stearothermophilus was shorter than that
      required for B. sporothermodurans and B. subtilis. In complex heat treatments
      (heating-holding-cooling), the survival curves of B. sporothermodurans and B.
      subtilis showed the same activation shoulders than those obtained under
      isothermal treatments and the activation shoulders were again absent in the case
      of G. stearothermophilus. Predictions fitted quite well the data obtained for B.
      sporothermodurans. In contrast, the data for B. subtilis showed half a log cycle
      more survival than expected and in the case of G. stearothermophilus, the
      survival curve obtained showed much higher inactivation than expected.

PMID- 25852135
TI  - l-Theanine prevents carbon tetrachloride-induced liver fibrosis via inhibition of
      nuclear factor kappaB and down-regulation of transforming growth factor beta and
      connective tissue growth factor.
AB  - Here we evaluated the ability of L-theanine in preventing experimental hepatic
      cirrhosis and investigated the roles of nuclear factor-kappaB (NF-kappaB)
      activation as well as transforming growth factor beta (TGF-beta) and connective
      tissue growth factor (CTGF) regulation. Experimental hepatic cirrhosis was
      established by the administration of carbon tetrachloride (CCl4) to rats (0.4
      g/kg, intraperitoneally, three times per week, for 8 weeks), and at the same
      time, adding L-theanine (8.0 mg/kg) to the drinking water. Rats had ad libitum
      access to water and food throughout the treatment period. CCl4 treatment promoted
      NF-kappaB activation and increased the expression of both TGF-beta and CTGF. CCl4
      increased the serum activities of alanine aminotransferase and gamma-glutamyl
      transpeptidase and the degree of lipid peroxidation, and it also induced a
      decrease in the glutathione and glutathione disulfide ratio. L-Theanine prevented
      increased expression of NF-kappaB and down-regulated the pro-inflammatory
      (interleukin (IL)-1beta and IL-6) and profibrotic (TGF-beta and CTGF) cytokines.
      Furthermore, the levels of messenger RNA encoding these proteins decreased in
      agreement with the expression levels. L-Theanine promoted the expression of the
      anti-inflammatory cytokine IL-10 and the fibrolytic enzyme metalloproteinase-13.
      Liver hydroxyproline contents and histopathological analysis demonstrated the
      anti-fibrotic effect of l-theanine. In conclusion, L-theanine prevents CCl4
      induced experimental hepatic cirrhosis in rats by blocking the main pro
      inflammatory and pro-fibrogenic signals.

PMID- 25852136
TI  - Metabolic changes in the urine of andrographolide sodium bisulfite-treated rats.
AB  - In recent years, andrographolide sodium bisulfite (ASB) has been reported to
      cause acute renal failure frequently in clinical practice. We hypothesized that
      changes in metabolic profile could have occurred after administration of ASB. To
      investigate the metabolic changes caused by ASB-induced nephrotoxicity,
      metabonomics method was utilized to depict the urine metabolic characteristics
      and find the specific urine biomarkers associated with ASB-induced
      nephrotoxicity. Sprague-Dawley rats were randomly assigned into three
      experimental groups. They received a single daily injection of vehicle (0.9%
      sodium chloride solution) or ASB at a dose of 100 or 600 mg kg(-1) day(-1) for 7
      days. Twelve-hour urine was collected after the last administration. The routine
      urinalysis was measured by a urine automatic analyzer while urinary metabolites
      were evaluated using gas chromatography/mass spectrometry. The acquired data were
      processed by multivariate principal component analysis (PCA), partial least
      squares discriminant analysis (PLS-DA), and orthogonal PLS-DA. After 7-day
      administration of ASB, the positive urine samples in protein, occult blood, and
      ketones were increased, presenting dose dependence. The PCA and PLS-DA models
      were capable of distinguishing the difference between ASB-treated group and
      control. Biomarkers such as 1,5-anhydroglucitol, d-erythro-sphingosine, and 2
      ketoadipate were identified as the most influential factors in ASB-induced
      nephrotoxicity. 

PMID- 25852137
TI  - Science and culture: Using fiction to make the case for basic research.

PMID- 25852139
TI  - Potential and challenges of patient-generated health data for high-quality cancer
      care.

PMID- 25852140
TI  - Patient Centeredness and Engagement in Quality-of-Care Oncology Research.
AB  - More than a decade after the Institute of Medicine (IOM) first studied the
      quality of cancer care, obstacles to achieving high-quality care remain, and
      studies suggest that cancer care is often not as patient centered, accessible,
      coordinated, or evidence based as it could be. Patients, their families, and
      clinicians face a wide range of complex and often confusing choices regarding
      their health and health care concerns and require trustworthy information to
      decide which options are best for them. The Patient-Centered Outcomes Research
      Institute (PCORI) strives to fund clinical comparative effectiveness research,
      guided by patients, caregivers, and the broader health care community, that will
      provide high-integrity, evidence-based information to help people make informed
      health care decisions. This mission is well aligned with the IOM's recent
      conceptual framework and corresponding recommendations that recognize that
      addressing the needs of patients with cancer and their families is the most
      important component of a high-quality cancer care delivery system. PCORI seeks
      the opportunity to partner with diverse interdisciplinary research teams who
      demonstrate a strong commitment to the inclusion and engagement of patients and
      stakeholders as they work to develop high-quality cancer care delivery systems.
      We see rich opportunities for such partnership in the cancer care community,
      given the wealth of well-established patient advocacy groups and organizations
      and cutting-edge research institutions, all of which are working toward the
      common goal of improving the quality of cancer care for patients and their
      families. This article and the project it describes provide an example of an
      avenue for advancing this goal. 

PMID- 25852141
TI  - Implementing a user-driven online quality improvement toolkit for cancer care.
AB  - PURPOSE: Peer-to-peer collaboration within integrated health systems requires a
      mechanism for sharing quality improvement lessons. The Veterans Health
      Administration (VA) developed online compendia of tools linked to specific cancer
      quality indicators. We evaluated awareness and use of the toolkits, variation
      across facilities, impact of social marketing, and factors influencing toolkit
      use. METHODS: A diffusion of innovations conceptual framework guided the
      collection of user activity data from the Toolkit Series SharePoint site and an
      online survey of potential Lung Cancer Care Toolkit users. RESULTS: The VA
      Toolkit Series site had 5,088 unique visitors in its first 22 months; 5% of users
      accounted for 40% of page views. Social marketing communications were correlated
      with site usage. Of survey respondents (n = 355), 54% had visited the site, of
      whom 24% downloaded at least one tool. Respondents' awareness of the lung cancer
      quality performance of their facility, and facility participation in quality
      improvement collaboratives, were positively associated with Toolkit Series site
      use. Facility-level lung cancer tool implementation varied widely across tool
      types. CONCLUSION: The VA Toolkit Series achieved widespread use and a high
      degree of user engagement, although use varied widely across facilities. The most
      active users were aware of and active in cancer care quality improvement. Toolkit
      use seemed to be reinforced by other quality improvement activities. A
      combination of user-driven tool creation and centralized toolkit development
      seemed to be effective for leveraging health information technology to spread
      disease-specific quality improvement tools within an integrated health care
      system.

PMID- 25852142
TI  - Supporting models to transition breast cancer survivors to primary care:
      formative evaluation of a cancer care Ontario initiative.
AB  - PURPOSE: Many breast cancer (BC) survivors continue to be seen by specialists for
      routine follow-up care despite growing evidence that transitioning appropriate BC
      survivors to primary care is safe and effective. We describe the formative
      evaluation of an initiative involving the development and implementation of
      sustainable models of follow-up care for BC survivors across 14 Regional Cancer
      Centers (RCC) in Ontario, Canada. METHODS: After extensive consultation, each RCC
      received catalyst funding for the initiative. Detailed work plans were developed
      locally and submitted to Cancer Care Ontario. Each region had a designated lead
      and support from primary care. Funding could be used to develop any aspect of the
      model. Formative evaluation of each model was conducted with descriptive analysis
      of the model created, including summative description of how resources were used,
      the number of survivors transitioned, and preliminary results from patient
      surveys of experience at transition. RESULTS: Each region developed a unique
      model that included clearly identified structures and processes of care. All
      regions used survivorship care plans and patient education materials. Three main
      models of follow-up care were developed: (1) direct to primary care, (2)
      transition clinic, and (3) shared care. A total of 3,418 BC survivors
      transitioned between March 2012 and September 2013. Patient experience surveys
      were distributed by 12 regions, gathering responses from 752 BC survivors, with
      85% reporting that they felt adequately prepared for the transition. CONCLUSION:
      Using the approach described, wide-scale transition of appropriate BC survivors
      from oncology-led practice is feasible over a fairly short timeframe.

PMID- 25852143
TI  - Variation in positron emission tomography use after colon cancer resection.
AB  - PURPOSE: Colon cancer surveillance guidelines do not routinely include positron
      emission tomography (PET) imaging; however, its use after surgical resection has
      been increasing. We evaluated the secular patterns of PET use after surgical
      resection of colon cancer among elderly patients and identified factors
      associated with its increasing use. PATIENTS AND METHODS: We used the SEER-linked
      Medicare database (July 2001 through December 2009) to establish a retrospective
      cohort of patients age >= 66 years who had undergone surgical resection for colon
      cancer. Postoperative PET use was assessed with the test for trends. Patient,
      tumor, and treatment characteristics were analyzed using univariable and
      multivariable logistic regression analyses. RESULTS: Of the 39,221 patients with
      colon cancer, 6,326 (16.1%) had undergone a PET scan within 2 years after
      surgery. The use rate steadily increased over time. The majority of PET scans had
      been performed within 2 months after surgery. Among patients who had undergone a
      PET scan, 3,644 (57.6%) had also undergone preoperative imaging, and 1,977
      (54.3%) of these patients had undergone reimaging with PET within 2 months after
      surgery. Marriage, year of diagnosis, tumor stage, preoperative imaging,
      postoperative visit to a medical oncologist, and adjuvant chemotherapy were
      significantly associated with increased PET use. CONCLUSION: PET use after colon
      cancer resection is steadily increasing, and further study is needed to
      understand the clinical value and effectiveness of PET scans and the reasons for
      this departure from guideline-concordant care.

PMID- 25852144
TI  - Random sampling of skewed distributions implies Taylor's power law of fluctuation
      scaling.
AB  - Taylor's law (TL), a widely verified quantitative pattern in ecology and other
      sciences, describes the variance in a species' population density (or other
      nonnegative quantity) as a power-law function of the mean density (or other
      nonnegative quantity): Approximately, variance = a(mean)(b), a > 0. Multiple
      mechanisms have been proposed to explain and interpret TL. Here, we show
      analytically that observations randomly sampled in blocks from any skewed
      frequency distribution with four finite moments give rise to TL. We do not claim
      this is the only way TL arises. We give approximate formulae for the TL
      parameters and their uncertainty. In computer simulations and an empirical
      example using basal area densities of red oak trees from Black Rock Forest, our
      formulae agree with the estimates obtained by least-squares regression. Our
      results show that the correlated sampling variation of the mean and variance of
      skewed distributions is statistically sufficient to explain TL under random
      sampling, without the intervention of any biological or behavioral mechanisms.
      This finding connects TL with the underlying distribution of population density
      (or other nonnegative quantity) and provides a baseline against which more
      complex mechanisms of TL can be compared. 

PMID- 25852145
TI  - Extended synaptotagmins (E-Syts): Architecture and dynamics of membrane contact
      sites revealed.

PMID- 25852146
TI  - A cytosolic heat shock protein 90 and cochaperone CDC37 complex is required for
      RIP3 activation during necroptosis.
AB  - Receptor-interacting protein kinase 3, RIP3, and a pseudokinase mixed lineage
      kinase-domain like protein, MLKL, constitute the core components of the
      necroptosis pathway, which causes programmed necrotic death in mammalian cells.
      Latent RIP3 in the cytosol is activated by several upstream signals including the
      related kinase RIP1, which transduces signals from the tumor necrosis factor
      (TNF) family of cytokines. We report here that RIP3 activation following the
      induction of necroptosis requires the activity of an HSP90 and CDC37 cochaperone
      complex. This complex physically associates with RIP3. Chemical inhibitors of
      HSP90 efficiently block necroptosis by preventing RIP3 activation. Cells with
      knocked down CDC37 were unable to respond to necroptosis stimuli. Moreover, an
      HSP90 inhibitor that is currently under clinical development as a cancer therapy
      was able to prevent systemic inflammatory response syndrome in rats treated with
      TNF-alpha. HSP90 and CDC37 cochaperone complex-mediated protein folding is thus
      an important part of the RIP3 activation process during necroptosis. 

PMID- 25852147
TI  - High-spin Mn-oxo complexes and their relevance to the oxygen-evolving complex
      within photosystem II.
AB  - The structural and electronic properties of a series of manganese complexes with
      terminal oxido ligands are described. The complexes span three different
      oxidation states at the manganese center (III-V), have similar molecular
      structures, and contain intramolecular hydrogen-bonding networks surrounding the
      Mn-oxo unit. Structural studies using X-ray absorption methods indicated that
      each complex is mononuclear and that oxidation occurs at the manganese centers,
      which is also supported by electron paramagnetic resonance (EPR) studies. This
      gives a high-spin Mn(V)-oxo complex and not a Mn(IV)-oxy radical as the most
      oxidized species. In addition, the EPR findings demonstrated that the Fermi
      contact term could experimentally substantiate the oxidation states at the
      manganese centers and the covalency in the metal-ligand bonding. Oxygen-17
      labeled samples were used to determine spin density within the Mn-oxo unit, with
      the greatest delocalization occurring within the Mn(V)-oxo species (0.45 spins on
      the oxido ligand). The experimental results coupled with density functional
      theory studies show a large amount of covalency within the Mn-oxo bonds. Finally,
      these results are examined within the context of possible mechanisms associated
      with photosynthetic water oxidation; specifically, the possible identity of the
      proposed high valent Mn-oxo species that is postulated to form during turnover is
      discussed. 

PMID- 25852148
TI  - Robust and sustained immune activation in human Ebola virus infection.

PMID- 25852149
TI  - Enzymatic functionalization of a nanobody using protein insertion technology.
AB  - Antibody-based products constitute one of the most attractive biological
      molecules for diagnostic, medical imagery and therapeutic purposes with very few
      side effects. Their development has become a major priority of biotech and
      pharmaceutical industries. Recently, a growing number of modified antibody-based
      products have emerged including fragments, multi-specific and conjugate
      antibodies. In this study, using protein engineering, we have functionalized the
      anti-hen egg-white lysozyme (HEWL) camelid VHH antibody fragment (cAb-Lys3), by
      insertion into a solvent-exposed loop of the Bacillus licheniformis beta
      lactamase BlaP. We showed that the generated hybrid protein conserved its
      enzymatic activity while the displayed nanobody retains its ability to inhibit
      HEWL with a nanomolar affinity range. Then, we successfully implemented the
      functionalized cAb-Lys3 in enzyme-linked immunosorbent assay, potentiometric
      biosensor and drug screening assays. The hybrid protein was also expressed on the
      surface of phage particles and, in this context, was able to interact
      specifically with HEWL while the beta-lactamase activity was used to monitor
      phage interactions. Finally, using thrombin-cleavage sites surrounding the
      permissive insertion site in the beta-lactamase, we reported an expression system
      in which the nanobody can be easily separated from its carrier protein.
      Altogether, our study shows that insertion into the BlaP beta-lactamase
      constitutes a suitable technology to functionalize nanobodies and allows the
      creation of versatile tools that can be used in innovative biotechnological
      assays. 

PMID- 25852150
TI  - Radioprotective effects of Sipunculus nudus L. polysaccharide combined with WR
      2721, rhIL-11 and rhG-CSF on radiation-injured mice.
AB  - This study investigated the radioprotective effect of Sipunculus nudus L.
      polysaccharide (SNP) in combination with WR-2721, rhIL-11 and rhG-CSF on
      irradiated mice. A total of 70 Imprinting Control Region (ICR) mice were divided
      into seven groups: the control group, the model group and five administration
      groups. All groups, except the control group, were exposed to a 5 Gy (60)Co gamma
      ray beam. Blood parameters [including white blood cell (WBC), red blood cell
      (RBC) and platelet counts and hemoglobin level] were assessed three days before
      irradiation, and the on the 3rd, 7th and 14th days after irradiation. Spleen,
      thymus and testicular indices, DNA contents of bone marrow cells, bone marrow
      nucleated cells, sperm counts, superoxide dismutase (SOD), malondialdehyde (MDA),
      testosterone and estradiol levels in the serum were assessed on the 14th day
      after irradiation. The combined administration of SNP, WR-2721, rhIL-11 and rhG
      CSF exerted synergistic recovery effects on peripheral blood WBC, RBC and
      platelet counts and hemoglobin levels in irradiated mice, and synergistic
      promotion effects on spleen, thymus, testicle, bone marrow nucleated cells and
      sperm counts in irradiated mice. The synergistic administration increased the
      serum SOD activities and serum testosterone content of irradiated mice, but
      synergy decreased the content of serum MDA and estradiol in irradiated mice.
      These results suggest that the combined administration of SNP, WR-2721, rhIL-11
      and rhG-CSF should increase the efficacy of these drugs for acute radiation
      sickness, protect immunity, hematopoiesis and the reproductive organs of
      irradiated-damaged mice, and improve oxidation resistance in the body. 

PMID- 25852152
TI  - Aortic root ring sign: multimodality imaging of aortic root abscess.

PMID- 25852151
TI  - Caudal epidural anesthesia during intracavitary brachytherapy for cervical
      cancer.
AB  - It has been suggested that pain control during intracavitary brachytherapy for
      cervical cancer is insufficient in most hospitals in Japan. Our hospital began
      using caudal epidural anesthesia during high-dose-rate (HDR) intracavitary
      brachytherapy in 2011. The purpose of the present study was to retrospectively
      investigate the effects of caudal epidural anesthesia during HDR intracavitary
      brachytherapy for cervical cancer patients. Caudal epidural anesthesia for 34
      cervical cancer patients was performed during HDR intracavitary brachytherapy
      between October 2011 and August 2013. We used the patients' self-reported Numeric
      Rating Scale (NRS) score at the first session of HDR intracavitary brachytherapy
      as a subjective evaluation of pain. We compared NRS scores of the patients with
      anesthesia with those of 30 patients who underwent HDR intracavitary
      brachytherapy without sacral epidural anesthesia at our hospital between May 2010
      and August 2011. Caudal epidural anesthesia succeeded in 33 patients (97%), and
      the NRS score was recorded in 30 patients. The mean NRS score of the anesthesia
      group was 5.17 +/- 2.97, significantly lower than that of the control group's
      6.80 +/- 2.59 (P = 0.035). The caudal epidural block resulted in no side-effects.
      Caudal epidural anesthesia is an effective and safe anesthesia option during HDR
      intracavitary brachytherapy for cervical cancer. 

PMID- 25852153
TI  - Lung metastasis and pheochromocytomas: Detection using FDG PET/CT.

PMID- 25852154
TI  - Long-term use of tamoxifen reduces the risk of dementia: a nationwide population
      based cohort study.
AB  - BACKGROUND: To assess the possible association between tamoxifen treatment and
      the subsequent risk of dementia in patients with breast cancer, a population
      based cohort study was conducted using the Taiwanese National Health Insurance
      Research Database. METHODS: The study cohort contained 24 197 patients diagnosed
      with breast cancer between 1 January 2000 and 31 December 2004. Among them, 16
      556 cases received tamoxifen treatment and 7641 did not. Four women without
      breast cancer were frequency matched to each case by age and index-year as the
      cancer-free group. The outcome of the analysis of is dementia. Hazard ratios
      (HRs) and 95% confidence intervals (CIs) were estimated using multivariate Cox
      proportional hazards regression models. RESULTS: Patients with breast cancer
      exhibited a similar risk of developing dementia (adjusted HR = 0.95, 95% CI =
      0.86-1.04) compared with the cancer-free group. In addition, among women
      diagnosed with breast cancer, tamoxifen users exhibited a significant 17% lower
      risk of dementia compared with those not using tamoxifen (adjusted HR = 0.83, 95%
      CI = 0.69-0.98), but the significant difference was limited to 5 years or more
      use (adjusted HR = 0.47, 95% CI = 0.32-0.69). Both tamoxifen and aromatase
      inhibitor use had a joint effect, with a significantly lower risk of dementia
      among patients. CONCLUSION: The results of this population-based cohort study
      suggest that long-term use of tamoxifen in patients with breast cancer is
      associated with a lower risk of dementia.

PMID- 25852155
TI  - MicroRNAs and DNA methylation as epigenetic regulators of mitosis, meiosis and
      spermiogenesis.
AB  - Spermatogenesis is composed of three distinctive phases, which include self
      renewal of spermatogonia via mitosis, spermatocytes undergoing meiosis I/II and
      post-meiotic development of haploid spermatids via spermiogenesis.
      Spermatogenesis also involves condensation of chromatin in the spermatid head
      before transformation of spermatids to spermatozoa. Epigenetic regulation refers
      to changes of heritably cellular and physiological traits not caused by
      modifications in the DNA sequences of the chromatin such as mutations. Major
      advances have been made in the epigenetic regulation of spermatogenesis. In this
      review, we address the roles and mechanisms of epigenetic regulators, with a
      focus on the role of microRNAs and DNA methylation during mitosis, meiosis and
      spermiogenesis. We also highlight issues that deserve attention for further
      investigation on the epigenetic regulation of spermatogenesis. More importantly,
      a thorough understanding of the epigenetic regulation in spermatogenesis will
      provide insightful information into the etiology of some unexplained infertility,
      offering new approaches for the treatment of male infertility. 

PMID- 25852156
TI  - Cell lineage allocation in equine blastocysts produced in vitro under varying
      glucose concentrations.
AB  - Equine embryos develop in vitro in the presence of high glucose concentrations,
      but little is known about their requirements for development. We evaluated the
      effect of glucose concentrations in medium on blastocyst development after ICSI.
      In experiment 1, there were no significant differences in rates of blastocyst
      formation among embryos cultured in our standard medium (DMEM/F-12), which
      contained >16 mM glucose, and those cultured in a minimal-glucose embryo culture
      medium (<1 mM; Global medium, GB), with either 0 added glucose for the first 5
      days, then 20 mM (0-20) or 20 mM for the entire culture period (20-20). In
      experiment 2, there were no significant differences in the rates of blastocyst
      development (31-46%) for embryos cultured in four glucose treatments in GB (0-10,
      0-20, 5-10, or 5-20). Blastocysts were evaluated by immunofluorescence for
      lineage-specific markers. All cells stained positively for POU5F1. An inner
      cluster of cells was identified that included presumptive primitive endoderm
      cells (GATA6-positive) and presumptive epiblast (EPI) cells. The 5-20 treatment
      resulted in a significantly lower number of presumptive EPI-lineage cells than
      the 0-20 treatment did. GATA6-positive cells appeared to be allocated to the
      primitive endoderm independent of the formation of an inner cell mass, as was
      previously hypothesized for equine embryos. These data demonstrate that equine
      blastocyst development is not dependent on high glucose concentrations during
      early culture; rather, environmental glucose may affect cell allocation. They
      also present the first analysis of cell lineage allocation in in vitro-fertilized
      equine blastocysts. These findings expand our understanding of the factors that
      affect embryo development in the horse. 

PMID- 25852157
TI  - Glycolytic dependency of high-level nitric oxide resistance and virulence in
      Staphylococcus aureus.
AB  - Staphylococcus aureus is a prolific human pathogen capable of causing severe
      invasive disease with a myriad of presentations. The ability of S. aureus to
      cause infection is strongly linked with its capacity to overcome the effects of
      innate immunity, whether by directly killing immune cells or expressing factors
      that diminish the impact of immune effectors. One such scenario is the induction
      of lactic acid fermentation by S. aureus in response to host nitric oxide (NO.).
      This fermentative activity allows S. aureus to balance redox during NO.-induced
      respiration inhibition. However, little is known about the metabolic substrates
      and pathways that support this activity. Here, we identify glycolytic hexose
      catabolism as being essential for S. aureus growth in the presence of high levels
      of NO.. We determine that glycolysis supports S. aureus NO. resistance by
      allowing for ATP and precursor metabolite production in a redox-balanced and
      respiration-independent manner. We further demonstrate that glycolysis is
      required for NO. resistance during phagocytosis and that increased levels of
      extracellular glucose limit the effectiveness of phagocytic killing by enhancing
      NO. resistance. Finally, we demonstrate that S. aureus glycolysis is essential
      for virulence in both sepsis and skin/soft tissue models of infection in a time
      frame consistent with the induction of innate immunity and host NO. production.
      IMPORTANCE: Staphylococcus aureus is a leading human bacterial pathogen capable
      of causing a wide variety of diseases that, as a result of antibiotic resistance,
      are very difficult to treat. The frequency of S. aureus tissue invasion suggests
      that this bacterium has evolved to resist innate immunity and grow using the
      nutrients present in otherwise sterile host tissue. We have identified glycolysis
      as an essential component of S. aureus virulence and attribute its importance to
      promoting nitric oxide resistance and growth under low oxygen conditions. Our
      data suggest that diabetics, a patient population characterized by excess serum
      glucose, may be more susceptible to S. aureus as a result of increased glucose
      availability. Furthermore, the essential nature of S. aureus glycolysis indicates
      that a newly developed glycolysis inhibitor may be a highly effective treatment
      for S. aureus infections.

PMID- 25852158
TI  - Coupled positive and negative feedbacks produce diverse gene expression patterns
      in colonies.
AB  - Formation of patterns is a common feature in the development of multicellular
      organism as well as of microbial communities. To investigate the formation of
      gene expression patterns in colonies, we build a mathematical model of two
      dimensional colony growth, where cells carry a coupled positive-and-negative
      feedback circuit. We demonstrate that the model can produce sectored, target
      (concentric), uniform, and scattered expression patterns of regulators, depending
      on gene expression dynamics and nutrient diffusion. We reconstructed the same
      regulatory structure in Escherichia coli cells and found gene expression patterns
      on the surface of colonies similar to the ones produced by the computer
      simulations. By comparing computer simulations and experimental results, we
      observed that very simple rules of gene expression can yield a spectrum of well
      defined patterns in a growing colony. Our results suggest that variations of the
      protein content among cells lead to a high level of heterogeneity in colonies.
      IMPORTANCE: Formation of patterns is a common feature in the development of
      microbial communities. In this work, we show that a simple genetic circuit
      composed of a positive-feedback loop and a negative-feedback loop can produce
      diverse expression patterns in colonies. We obtained similar sets of gene
      expression patterns in the simulations and in the experiments. Because the
      combination of positive feedback and negative feedback is common in intracellular
      molecular networks, our results suggest that the protein content of cells is
      highly diversified in colonies.

PMID- 25852159
TI  - Genetic basis of persister tolerance to aminoglycosides in Escherichia coli.
AB  - Persisters are dormant variants that form a subpopulation of drug-tolerant cells
      largely responsible for the recalcitrance of chronic infections. However, our
      understanding of the genetic basis of antibiotic tolerance remains incomplete. In
      this study, we applied transposon sequencing (Tn-Seq) to systematically
      investigate the mechanism of aminoglycoside tolerance in Escherichia coli. We
      constructed a highly saturated transposon library that covered the majority of E.
      coli genes and promoter regions and exposed a stationary-phase culture to a
      lethal dose of gentamicin. Tn-Seq was performed to evaluate the survival of each
      mutant to gentamicin exposure. We found that the disruption of several distinct
      pathways affected gentamicin tolerance. We identified 105 disrupted gene/promoter
      regions with a more than 5-fold reduction in gentamicin tolerance and 37 genes
      with a more than 5-fold increased tolerance. Functional cluster analysis suggests
      that deficiency in motility and amino acid synthesis significantly diminished
      persisters tolerant to gentamicin, without changing the MIC. Amino acid
      auxotrophs, including serine, threonine, glutamine, and tryptophan auxotrophs,
      exhibit strongly decreased tolerance to gentamicin, which cannot be restored by
      supplying the corresponding amino acids to the culture. Interestingly, supplying
      these amino acids to wild-type E. coli sensitizes stationary-phase cells to
      gentamicin, possibly through the inhibition of amino acid synthesis. In addition,
      we found that the deletion of amino acid synthesis genes significantly increases
      gentamicin uptake in stationary phase, while the deletion of flagellar genes does
      not affect gentamicin uptake. We conclude that activation of motility and amino
      acid biosynthesis contributes to the formation of persisters tolerant to
      gentamicin. IMPORTANCE: Persisters are responsible for the recalcitrance of
      chronic infections to antibiotics. The pathways of persister formation in E. coli
      are redundant, and our understanding of the mechanism of persister formation is
      incomplete. Using a highly saturated transposon insertion library, we
      systematically analyzed the contribution of different cellular processes to the
      formation of persisters tolerant to aminoglycosides. Unexpectedly, we found that
      activation of amino acid synthesis and motility strongly contributes to persister
      formation. The approach used in this study leads to an understanding of
      aminoglycoside tolerance and provides a general method to identify genes
      affecting persister formation.

PMID- 25852160
TI  - Characterization of H5N1 influenza virus variants with hemagglutinin mutations
      isolated from patients.
AB  - A change in viral hemagglutinin (HA) receptor binding specificity from alpha2,3-
      to alpha2,6-linked sialic acid is necessary for highly pathogenic avian influenza
      (AI) virus subtype H5N1 to become pandemic. However, details of the human
      adaptive change in the H5N1 virus remain unknown. Our database search of H5N1
      clade 2.2.1 viruses circulating in Egypt identified multiple HA mutations that
      had been selected in infected patients. Using reverse genetics, we found that
      increases in both human receptor specificity and the HA pH threshold for membrane
      fusion were necessary to facilitate replication of the virus variants in human
      airway epithelia. Furthermore, variants with enhanced replication in human cells
      had decreased HA stability, apparently to compensate for the changes in viral
      receptor specificity and membrane fusion activity. Our findings showed that H5N1
      viruses could rapidly adapt to growth in the human airway microenvironment by
      altering their HA properties in infected patients and provided new insights into
      the human-adaptive mechanisms of AI viruses. IMPORTANCE: Circulation between bird
      and human hosts may allow H5N1 viruses to acquire amino acid changes that
      increase fitness for human infections. However, human-adaptive changes in H5N1
      viruses have not been adequately investigated. In this study, we found that
      multiple HA mutations were actually selected in H5N1-infected patients and that
      H5N1 variants with some of these HA mutations had increased human-type receptor
      specificity and increased HA membrane fusion activity, both of which are
      advantageous for viral replication in human airway epithelia. Furthermore, HA
      mutants selected during viral replication in patients were likely to have less HA
      stability, apparently as a compensatory mechanism. These results begin to clarify
      the picture of the H5N1 human-adaptive mechanism.

PMID- 25852162
TI  - Reply to '"Mycobacterium indicus pranii" is a strain of Mycobacterium
      intracellulare': "M. indicus pranii" is a distinct strain, not derived from M.
      intracellulare, and is an organism at an evolutionary transition point between a
      fast grower and slow grower.

PMID- 25852161
TI  - Over 150 years of long-term fertilization alters spatial scaling of microbial
      biodiversity.
AB  - Spatial scaling is a critical issue in ecology, but how anthropogenic activities
      like fertilization affect spatial scaling is poorly understood, especially for
      microbial communities. Here, we determined the effects of long-term fertilization
      on the spatial scaling of microbial functional diversity and its relationships to
      plant diversity in the 150-year-old Park Grass Experiment, the oldest continuous
      grassland experiment in the world. Nested samples were taken from plots with
      contrasting inorganic fertilization regimes, and community DNAs were analyzed
      using the GeoChip-based functional gene array. The slopes of microbial gene-area
      relationships (GARs) and plant species-area relationships (SARs) were estimated
      in a plot receiving nitrogen (N), phosphorus (P), and potassium (K) and a control
      plot without fertilization. Our results indicated that long-term inorganic
      fertilization significantly increased both microbial GARs and plant SARs.
      Microbial spatial turnover rates (i.e., z values) were less than 0.1 and were
      significantly higher in the fertilized plot (0.0583) than in the control plot
      (0.0449) (P < 0.0001). The z values also varied significantly with different
      functional genes involved in carbon (C), N, P, and sulfur (S) cycling and with
      various phylogenetic groups (archaea, bacteria, and fungi). Similarly, the plant
      SARs increased significantly (P < 0.0001), from 0.225 in the control plot to
      0.419 in the fertilized plot. Soil fertilization, plant diversity, and spatial
      distance had roughly equal contributions in shaping the microbial functional
      community structure, while soil geochemical variables contributed less. These
      results indicated that long-term agricultural practice could alter the spatial
      scaling of microbial biodiversity. IMPORTANCE: Determining the spatial scaling of
      microbial biodiversity and its response to human activities is important but
      challenging in microbial ecology. Most studies to date are based on different
      sites that may not be truly comparable or on short-term perturbations, and hence,
      the results observed could represent transient responses. This study examined the
      spatial patterns of microbial communities in response to different fertilization
      regimes at the Rothamsted Research Experimental Station, which has become an
      invaluable resource for ecologists, environmentalists, and soil scientists. The
      current study is the first showing that long-term fertilization has dramatic
      impacts on the spatial scaling of microbial communities. By identifying the
      spatial patterns in response to long-term fertilization and their underlying
      mechanisms, this study makes fundamental contributions to predictive
      understanding of microbial biogeography.

PMID- 25852163
TI  - Intrahost dynamics of antiviral resistance in influenza A virus reflect complex
      patterns of segment linkage, reassortment, and natural selection.
AB  - Resistance following antiviral therapy is commonly observed in human influenza
      viruses. Although this evolutionary process is initiated within individual hosts,
      little is known about the pattern, dynamics, and drivers of antiviral resistance
      at this scale, including the role played by reassortment. In addition, the short
      duration of human influenza virus infections limits the available time window in
      which to examine intrahost evolution. Using single-molecule sequencing, we
      mapped, in detail, the mutational spectrum of an H3N2 influenza A virus
      population sampled from an immunocompromised patient who shed virus over a 21
      month period. In this unique natural experiment, we were able to document the
      complex dynamics underlying the evolution of antiviral resistance. Individual
      resistance mutations appeared weeks before they became dominant, evolved
      independently on cocirculating lineages, led to a genome-wide reduction in
      genetic diversity through a selective sweep, and were placed into new
      combinations by reassortment. Notably, despite frequent reassortment,
      phylogenetic analysis also provided evidence for specific patterns of segment
      linkage, with a strong association between the hemagglutinin (HA)- and matrix (M)
      encoding segments that matches that previously observed at the epidemiological
      scale. In sum, we were able to reveal, for the first time, the complex
      interaction between multiple evolutionary processes as they occur within an
      individual host. IMPORTANCE: Understanding the evolutionary forces that shape the
      genetic diversity of influenza virus is crucial for predicting the emergence of
      drug-resistant strains but remains challenging because multiple processes occur
      concurrently. We characterized the evolution of antiviral resistance in a single
      persistent influenza virus infection, representing the first case in which
      reassortment and the complex patterns of drug resistance emergence and evolution
      have been determined within an individual host. Deep-sequence data from multiple
      time points revealed that the evolution of antiviral resistance reflects a
      combination of frequent mutation, natural selection, and a complex pattern of
      segment linkage and reassortment. In sum, these data show how immunocompromised
      hosts may help reveal the drivers of strain emergence.

PMID- 25852164
TI  - The transcription factor FoxK participates with Nup98 to regulate antiviral gene
      expression.
AB  - Upon infection, pathogen recognition leads to a rapidly activated gene expression
      program that induces antimicrobial effectors to clear the invader. We recently
      found that Nup98 regulates the expression of a subset of rapidly activated
      antiviral genes to restrict disparate RNA virus infections in Drosophila by
      promoting RNA polymerase occupancy at the promoters of these antiviral genes. How
      Nup98 specifically targets these loci was unclear; however, it is known that
      Nup98 participates with transcription factors to regulate developmental-gene
      activation. We reasoned that additional transcription factors may facilitate the
      Nup98-dependent expression of antiviral genes. In a genome-wide RNA interference
      (RNAi) screen, we identified a relatively understudied forkhead transcription
      factor, FoxK, as active against Sindbis virus (SINV) in Drosophila. Here we find
      that FoxK is active against the panel of viruses that are restricted by Nup98,
      including SINV and vesicular stomatitis virus (VSV). Mechanistically, we show
      that FoxK coordinately regulates the Nup98-dependent expression of antiviral
      genes. Depletion of FoxK significantly reduces Nup98-dependent induction of
      antiviral genes and reduces the expression of a forkhead response element
      containing luciferase reporter. Together, these data show that FoxK-mediated
      activation of gene expression is Nup98 dependent. We extended our studies to
      mammalian cells and found that the mammalian ortholog FOXK1 is antiviral against
      two disparate RNA viruses, SINV and VSV, in human cells. Interestingly, FOXK1
      also plays a role in the expression of antiviral genes in mammals: depletion of
      FOXK1 attenuates virus-inducible interferon-stimulated response element (ISRE)
      reporter expression. Overall, our results demonstrate a novel role for FOXK1 in
      regulating the expression of antiviral genes, from insects to humans. IMPORTANCE:
      Innate immunity is characterized by rapid gene expression programs, from insects
      to mammals. Furthermore, we find that Nup98, known for its roles in the nuclear
      pore, plays a noncanonical role in binding the promoters and poising a subset of
      loci for rapid antiviral gene induction. It was unclear how Nup98 accesses these
      specific genes, and we here demonstrate that Nup98 cooperates with the
      transcription factor FoxK to regulate this gene expression program. Depletion of
      FoxK specifically reduces the induction of Nup98-dependent genes. Further, we
      find that the antiviral function of FoxK is conserved, as the human ortholog
      FOXK1 is also antiviral and regulates gene expression from virus-induced
      promoters. Although other forkhead transcription factors have been implicated in
      immunity, a role for FoxK in antiviral defense was previously unappreciated. Our
      findings reveal a conserved and novel role for FoxK in coordinating with Nup98 to
      promote a robust and complex antiviral transcriptional response.

PMID- 25852165
TI  - USA300 and USA500 clonal lineages of Staphylococcus aureus do not produce a
      capsular polysaccharide due to conserved mutations in the cap5 locus.
AB  - The surface capsular polysaccharide (CP) is a virulence factor that has been used
      as an antigen in several successful vaccines against bacterial pathogens. A
      vaccine has not yet been licensed against Staphylococcus aureus, although two
      multicomponent vaccines that contain CP antigens are in clinical trials. In this
      study, we evaluated CP production in USA300 methicillin-resistant S. aureus
      (MRSA) isolates that have become the predominant community-associated MRSA clones
      in the United States. We found that all 167 USA300 MRSA and 50 USA300 methicillin
      susceptible S. aureus (MSSA) isolates were CP negative (CP(-)). Moreover, all 16
      USA500 isolates, which have been postulated to be the progenitor lineage of
      USA300, were also CP(-). Whole-genome sequence analysis of 146 CP(-) USA300 MRSA
      isolates revealed they all carry a cap5 locus with 4 conserved mutations compared
      with strain Newman. Genetic complementation experiments revealed that three of
      these mutations (in the cap5 promoter, cap5D nucleotide 994, and cap5E nucleotide
      223) ablated CP production in USA300 and that Cap5E75 Asp, located in the
      coenzyme-binding domain, is essential for capsule production. All but three
      USA300 MSSA isolates had the same four cap5 mutations found in USA300 MRSA
      isolates. Most isolates with a USA500 pulsotype carried three of these four
      USA300-specific mutations, suggesting the fourth mutation occurred in the USA300
      lineage. Phylogenetic analysis of the cap loci of our USA300 isolates as well as
      publicly available genomes from 41 other sequence types revealed that the USA300
      specific cap5 mutations arose sequentially in S. aureus in a common ancestor of
      USA300 and USA500 isolates. IMPORTANCE: The USA300 MRSA clone emerged as a
      community-associated pathogen in the United States nearly 20 years ago. Since
      then, it has rapidly disseminated and now causes health care-associated
      infections. This study shows that the CP-negative (CP(-)) phenotype has persisted
      among USA300 isolates and is a universal and characteristic trait of this highly
      successful MRSA lineage. It is important to note that a vaccine consisting solely
      of CP antigens would not likely demonstrate high efficacy in the U.S. population,
      where about half of MRSA isolates comprise USA300. Moreover, conversion of a
      USA300 strain to a CP-positive (CP(+)) phenotype is unlikely in vivo or in vitro
      since it would require the reversion of 3 mutations. We have also established
      that USA300 MSSA isolates and USA500 isolates are CP(-) and provide new insight
      into the evolution of the USA300 and USA500 lineages.

PMID- 25852166
TI  - Effect of Weight Loss on Postural Changes in Pulmonary Function in Obese
      Subjects: A Longitudinal Study.
AB  - BACKGROUND: Postural changes are known to affect normal lung volumes. A reduction
      in sitting to supine functional residual capacity (FRC) is well-described in non
      obese subjects adopting a supine position. However, postural changes in lung
      volumes in the obese require further exploration. We aimed to longitudinally
      address the effects of weight loss on postural changes in lung volumes and
      pulmonary function in obese subjects. We tested the hypothesis that supine
      reduction in FRC would be absent in morbid obesity and recovered upon weight
      loss. METHODS: This was a prospective, observational, longitudinal study.
      Consecutive morbidly obese adults (N = 12, age: 44 +/- 14 y, body mass index: 45
      +/- 5 kg/m(2)) enrolled in a bariatric surgery program were included. Standard
      pulmonary function tests and blood gas analysis were performed both before and 1
      y after surgery. Pulmonary function was assessed in both the sitting and supine
      position using spirometry and multi-breath helium dilution. Parameters recorded
      before and after weight loss were compared. The main outcome measure was FRC.
      RESULTS: Ten subjects were retested 1 y after surgery (body mass index: 31 +/- 5
      kg/m(2)). FRC was not affected by change in posture before surgery. Supine
      reduction in FRC was observed after weight loss (DeltaFRC: -0.6 +/- 0.4 L,
      sitting vs supine, P = .002). Pulmonary gas exchange improved (alveolar-to
      arterial oxygen partial pressure difference: -8 +/- 11 mm Hg, P = .035).
      CONCLUSIONS: Although postural change in FRC is absent when the morbidly obese
      adopt a supine position, supine reduction in FRC can be recovered following
      gastroplasty-induced weight loss, despite residual mild to moderate obesity. This
      also shows that mild to moderate obesity may affect supine FRC more than morbid
      obesity. (ClinicalTrials.gov registration NCT02207192.).

PMID- 25852168
TI  - Bronchoconstriction in response to deep inhalation during spirometry testing.

PMID- 25852167
TI  - Use of Accelerometry to Monitor Physical Activity in Critically Ill Subjects: A
      Systematic Review.
AB  - Medical management of critically ill patients often incorporates prolonged bed
      rest, which, in combination with the underlying illness, results in global muscle
      weakness and atrophy. Recent evidence has demonstrated improvements in clinical
      and functional outcomes when exercise and physical activity are incorporated
      early in the management of ICU patients. Accurate monitoring of ICU patients'
      physical activity is essential for proper prescription and escalation of activity
      levels. Accelerometry is a technique used to measure physical activity and has
      been validated in several ambulatory populations. However, its use in critically
      ill, hospitalized patients with poor functional mobility is limited. In this
      review, we focus on the few studies assessing the use of accelerometry to measure
      physical activity in the care of mechanically ventilated adult ICU patients. The
      selected literature demonstrates that accelerometry correlates well with direct
      observation in reporting frequency and duration of various types of physical
      activity (rolling, sitting up, transferring, walking), but cannot differentiate
      various intensities of activity or whether movements are voluntary or involuntary
      with respect to effort. Thus, although accelerometry may serve as a useful
      adjunct in reporting temporality of physical activity in critically ill patients,
      other objective information may be needed to accurately record frequency,
      duration, and intensity of activity in this population.

PMID- 25852169
TI  - Concordant dysregulation of miR-5p and miR-3p arms of the same precursor microRNA
      may be a mechanism in inducing cell proliferation and tumorigenesis: a lung
      cancer study.
AB  - A precursor microRNA (miRNA) has two arms: miR-5p and miR-3p (miR-5p/-3p).
      Depending on the tissue or cell types, both arms can become functional. However,
      little is known about their coregulatory mechanisms during the tumorigenic
      process. Here, by using the large-scale miRNA expression profiles of five cancer
      types, we revealed that several of miR-5p/-3p arms were concordantly dysregulated
      in each cancer. To explore possible coregulatory mechanisms of concordantly
      dysregulated miR-5p/-3p pairs, we developed a robust computational framework and
      applied it to lung cancer data. The framework deciphers miR-5p/-3p coregulated
      protein interaction networks critical to lung cancer development. As a novel part
      in the method, we uniquely applied the second-order partial correlation to
      minimize false-positive regulations. Using 279 matched miRNA and mRNA expression
      profiles extracted from tumor and normal lung tissue samples, we identified 17
      aberrantly expressed miR-5p/-3p pairs that potentially modulate the gene
      expression of 35 protein complexes. Functional analyses revealed that these
      complexes are associated with cancer-related biological processes, suggesting the
      oncogenic potential of the reported miR-5p/-3p pairs. Specifically, we revealed
      that the reduced expression of miR-145-5p/-3p pair potentially contributes to
      elevated expression of genes in the "FOXM1 transcription factor network" pathway,
      which may consequently lead to uncontrolled cell proliferation. Subsequently, the
      regulation of miR-145-5p/-3p in the FOXM1signaling pathway was validated by a
      cohort of 104 matched miRNA and protein (reverse-phase protein array) expression
      profiles in lung cancer. In summary, our computational framework provides a novel
      tool to study miR-5p/-3p coregulatory mechanisms in cancer and other diseases. 

PMID- 25852171
TI  - Identification of stable reference genes in differentiating human pluripotent
      stem cells.
AB  - Reference genes, often referred to as housekeeping genes (HKGs), are frequently
      used to normalize gene expression data based on the assumption that they are
      expressed at a constant level in the cells. However, several studies have shown
      that there may be a large variability in the gene expression levels of HKGs in
      various cell types. In a previous study, employing human embryonic stem cells
      (hESCs) subjected to spontaneous differentiation, we observed that the expression
      of commonly used HKG varied to a degree that rendered them inappropriate to use
      as reference genes under those experimental settings. Here we present a
      substantially extended study of the HKG signature in human pluripotent stem cells
      (hPSC), including nine global gene expression datasets from both hESC and human
      induced pluripotent stem cells, obtained during directed differentiation toward
      endoderm-, mesoderm-, and ectoderm derivatives. Sets of stably expressed genes
      were compiled, and a handful of genes (e.g., EID2, ZNF324B, CAPN10, and RABEP2)
      were identified as generally applicable reference genes in hPSCs across all cell
      lines and experimental conditions. The stability in gene expression profiles was
      confirmed by reverse transcription quantitative PCR analysis. Taken together, the
      current results suggest that differentiating hPSCs have a distinct HKG signature,
      which in some aspects is different from somatic cell types, and underscore the
      necessity to validate the stability of reference genes under the actual
      experimental setup used. In addition, the novel putative HKGs identified in this
      study can preferentially be used for normalization of gene expression data
      obtained from differentiating hPSCs. 

PMID- 25852170
TI  - Exoelectrogenic capacity of host microbiota predicts lymphocyte recruitment to
      the gut.
AB  - Electrotaxis, directional cell movement in response to an electric potential, has
      been demonstrated in a wide range of cell types including lymphocytes.
      Exoelectrogens, microorganisms capable of generating electrical currents, have
      been identified in microbial fuel cells. However, no studies have investigated
      exoelectrogenic microbes in fresh feces or the effects of an exoelectrogenic
      microbiota on the host organism. Here we show that commensal gut microbial
      populations differ in their capacity for electrical current production by
      exoelectrogens and that those differences are predictive of increased lymphocyte
      trafficking to the gut in vivo, despite the lack of increased production of
      canonical lymphocyte-specific chemokines. Additionally, we demonstrate that the
      difference in current production between mice purchased from different commercial
      sources correlates reproducibly with the presence or absence of segmented
      filamentous bacteria, and while our data do not support a direct role for
      segmented filamentous bacteria in ex vivo current production, an exoelectrogenic
      microbiota can be transferred in vivo via mucosa-associated bacteria present in
      the ileum. Moreover, we detect upregulation of microbial genes associated with
      extracellular electron transfer in feces of mice colonized with exoelectrogenic
      microbiota containing segmented filamentous bacteria. While still correlative,
      these results suggest a novel means by which the gut microbiota modulates the
      recruitment of cells of the immune system to the gut.

PMID- 25852173
TI  - Influenza vaccine efficacy.

PMID- 25852174
TI  - Better treatment for depression.

PMID- 25852175
TI  - Better treatment for depression.

PMID- 25852176
TI  - Better treatment for depression.

PMID- 25852177
TI  - Penicillin VK oral suspension.

PMID- 25852178
TI  - Figure caption.

PMID- 25852179
TI  - Forum.

PMID- 25852180
TI  - Traumatization in Deaf and Hard-of-Hearing Adult Psychiatric Outpatients.
AB  - Deaf and hard-of-hearing persons are at risk for experiencing traumatic events
      and such experiences are associated with symptoms of mental disorder. We
      investigated the prevalence of traumatic events and subsequent traumatization in
      adults referred to specialized psychiatric outpatient units for deaf and hard-of
      hearing patients. Sixty-two patients were diagnosed with mental disorders and
      assessed for potential traumatic experiences in their preferred language and mode
      of communication using instruments translated into Norwegian Sign Language. All
      patients reported traumatic events, with a mean of 6.2 different types; 85%
      reported subsequent traumatization not significantly associated with either
      residential school setting or communicative competence of childhood caregivers.
      Traumatization patterns in both sexes were similar to those in hearing clinical
      samples. Findings indicate that psychiatric intake interviews should routinely
      assess potentially traumatic events and their impacts, and that mental health
      professionals working with deaf and hard-of-hearing patients should be able to
      treat trauma-related disorders. 

PMID- 25852181
TI  - Radiation doses in chest, abdomen and pelvis CT procedures.
AB  - Computed tomography (CT) scanning is recognised as a high-radiation dose modality
      and estimated to be 17 % of the radiological procedure and responsible for 70 %
      of medical radiation exposure. Although diagnostic X rays provide great benefits,
      their use involves some risk for developing cancer. The objectives of this study
      are to estimate radiation doses during chest, abdomen and pelvis CT. A total of
      51 patients were examined for the evaluation of metastasis of a diagnosed primary
      tumour during 4 months. A calibrated CT machine from Siemens 64 slice was used.
      The mean age was 48.0 +/- 18.6 y. The mean patient weight was 73.8 +/- 16.1 kg.
      The mean dose-length product was 1493.8 +/- 392.1 mGy cm, Volume CT dose index
      (CTDI vol) was 22.94 +/- 5.64 mGy and the mean effective dose was 22.4 +/- 5.9
      mSv per procedure. The radiation dose per procedure was higher as compared with
      previous studies. Therefore, the optimisation of patient's radiation doses is
      required in order to reduce the radiation risk.

PMID- 25852182
TI  - Radiation dose levels for conventional chest and abdominal X-ray procedures in
      elected hospitals in Sudan.
AB  - This study aimed to assess patient entrance surface air kerma (ESAK) during chest
      and abdominal X-ray procedures in screen film radiography (SFR) and computed
      radiography (CR) to establish dose reference levels. Patients' doses were
      measured in five hospitals for a total of 196 patients. ESAK was calculated from
      exposure parameters using DosCal software. The X-ray tube output (mGy mAs(-1)),
      accuracy of exposure factors, linearity and reproducibility were measured using
      an Unfors Xi dosimeter. The overall mean and range of ESAK during chest X-ray
      were 0.6 +/- 0.3 (0.1-1.3) mGy, while for abdominal X-rays they were 4.0 +/- 3.2
      (1.3-9.2) mGy. Hospital with a CR system was found to use relatively higher
      doses. Dose values for abdominal X-ray procedures were comparable with previous
      studies. The dose for chest X-ray procedure was higher by a factor of 2-3
      compared with the current international reference levels.

PMID- 25852183
TI  - Examination of the relevance of using radiochromic films in measuring entrance
      skin dose distribution in conventional digital mammography.
AB  - Based on manufacturer specifications, radiochromic films are sensitive enough to
      be used for dosimetry in digital mammography (DM). The aim of this work was to
      study the feasibility of measuring entrance surface dose (ESD) distribution using
      Gafchromic XR-QA2 films. The films were irradiated following a standard clinical
      two-view screening mammography protocol using a full-field digital mammography
      (FFDM) imaging system. The films were then digitised using a flatbed scanner. The
      calibration curve relating the readings from a calibrated ionisation chamber and
      the films' net optical density (NOD) could not be obtained. The examination of
      the calibration data revealed non-sensitivity of the films to resolve dose
      differences below 20 mGy at 28 kVp. Therefore, radiochromic films were found not
      to be suitable for measuring ESD profiles in DM. A 2D map of the NOD of the
      irradiated films obtained using in-house developed MATLAB computer program is
      presented. 

PMID- 25852184
TI  - Focus issue: Tackling reproducibility and accuracy in cell signaling experiments.
AB  - With contributions from the Board of Reviewing Editors and the Chief Scientific
      Editor, Science Signaling highlights some common concerns surrounding
      reproducibility and issues related to appropriate methodological considerations
      for accurately quantifying and then modeling regulatory phenomena. Specific
      topics include sources of error, understanding biological "n" and the application
      of appropriate statistical analyses, quantitative Western blotting, quantitative
      mass spectrometry-based proteomics, and parameterization for establishing
      quantitative models of cellular networks. 

PMID- 25852185
TI  - Reproducibility in science.
AB  - The issue of reproducibility and reliability in science has come to the forefront
      in light of several high-profile studies that could not be reproduced. Whereas
      some errors in reliability can be attributed to the application of new techniques
      that have unappreciated caveats, some problems with reproducibility lie in the
      climate of intense pressure for funding and to publish faced by many researchers.

PMID- 25852186
TI  - Criteria for biological reproducibility: what does "n" mean?
AB  - This Focus tackles the issue of technical versus biological replicates, what
      constitutes appropriate biological replicates, and appropriate statistical
      analysis for data with small sample sizes. 

PMID- 25852187
TI  - Good practices for building dynamical models in systems biology.
AB  - Dynamic models can offer deep understanding of information processing mechanisms
      in physiology, cell signaling, and biological regulation when they are
      appropriately detailed. Here, we describe some of the key aspects of the model
      building process, including proper parameterization and error analysis, as well
      as common mistakes, such as model-tweaking and oversimplification, which can
      decrease the value of the models. 

PMID- 25852188
TI  - Quantitative mass spectrometry of posttranslational modifications: keys to
      confidence.
AB  - Posttranslational modifications (PTMs) of proteins represent an important level
      of cellular control. They participate in the efficient transduction of signals
      and form the basis of long-term cellular memory, allowing cells to adapt to a
      rapidly changing environment. More than 200 different PTMs have been described
      that affect many aspects of protein functions, and the importance of these
      modifications is evident from the number of diseases that arise from their
      deregulation. The proteome-wide analysis of certain PTMs, such as
      phosphorylation, acetylation, glycosylation, methylation, ubiquitination, and
      sumoylation, has become a standard procedure in many laboratories. We highlight
      and discuss some important aspects of systems-wide PTM analyses using mass
      spectrometry-based methods. 

PMID- 25852189
TI  - An analysis of critical factors for quantitative immunoblotting.
AB  - Immunoblotting (also known as Western blotting) combined with digital image
      analysis can be a reliable method for analyzing the abundance of proteins and
      protein modifications, but not every immunoblot-analysis combination produces an
      accurate result. I illustrate how sample preparation, protocol implementation,
      detection scheme, and normalization approach profoundly affect the quantitative
      performance of immunoblotting. This study implemented diagnostic experiments that
      assess an immunoblot-analysis workflow for accuracy and precision. The results
      showed that ignoring such diagnostics can lead to pseudoquantitative immunoblot
      data that markedly overestimate or underestimate true differences in protein
      abundance. 

PMID- 25852190
TI  - Integrative analysis of kinase networks in TRAIL-induced apoptosis provides a
      source of potential targets for combination therapy.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an endogenous
      secreted peptide and, in preclinical studies, preferentially induces apoptosis in
      tumor cells rather than in normal cells. The acquisition of resistance in cells
      exposed to TRAIL or its mimics limits their clinical efficacy. Because kinases
      are intimately involved in the regulation of apoptosis, we systematically
      characterized kinases involved in TRAIL signaling. Using RNA interference (RNAi)
      loss-of-function and cDNA overexpression screens, we identified 169 protein
      kinases that influenced the dynamics of TRAIL-induced apoptosis in the colon
      adenocarcinoma cell line DLD-1. We classified the kinases as sensitizers or
      resistors or modulators, depending on the effect that knockdown and
      overexpression had on TRAIL-induced apoptosis. Two of these kinases that were
      classified as resistors were PX domain-containing serine/threonine kinase (PXK)
      and AP2-associated kinase 1 (AAK1), which promote receptor endocytosis and may
      enable cells to resist TRAIL-induced apoptosis by enhancing endocytosis of the
      TRAIL receptors. We assembled protein interaction maps using mass spectrometry
      based protein interaction analysis and quantitative phosphoproteomics. With these
      protein interaction maps, we modeled information flow through the networks and
      identified apoptosis-modifying kinases that are highly connected to regulated
      substrates downstream of TRAIL. The results of this analysis provide a resource
      of potential targets for the development of TRAIL combination therapies to
      selectively kill cancer cells. 

PMID- 25852192
TI  - Limbic pathway lesions in patients with multiple sclerosis.
AB  - BACKGROUND: Multiple sclerosis (MS) is a well-known demyelinating disease to
      cause cognitive dysfunction. The limbic system, relevant to memory, can be easily
      overlooked in conventional magnetic resonance imaging (MRI). PURPOSE: To
      investigate the distribution and frequency of demyelinating lesions affecting
      white matter connections of the limbic system based on localization with
      diffusion tensor imaging (DTI)-derived fractional anisotropy (FA) color maps
      compared to three-dimensional T2-weighted (T2W) and FLAIR volumes in MS patients.
      MATERIAL AND METHODS: One hundred and fifty patients with a known diagnosis of MS
      were identified for this Health Insurance Portability and Accountability (HIPAA)
      compliant retrospective cross-sectional study. DTI-derived FA color maps, co
      registered to T2W and FLAIR images, were analyzed for lesions affecting the three
      white matter tracts of the limbic system including cingulum, fornix, and
      mammilothalamic tracts by two investigators. The approximate location of the
      lesions on FLAIR was always confirmed on the co-registered DTI-derived FA color
      maps. RESULTS: Of the 150 patients analyzed, 14.6% had cingulum lesions, 2.6% had
      fornix lesions, and 2.6% had mammilothalamic tract lesions; 21.3% of patients had
      at least one of the three tracts affected. CONCLUSION: A relatively high
      frequency of lesions involving the limbic tracts may explain memory deficits and
      emotional dysfunction commonly experienced by patients with MS. The combined
      information from T2W, FLAIR, and DTI-derived FA color map allowed for more
      accurate localization of lesions affecting the major white matter tracts of the
      limbic system.

PMID- 25852194
TI  - Estimating effective dose from 3D imaging with interventional fluoroscopy systems
      using limited exposure data.
AB  - BACKGROUND: Estimations of the effective dose from three-dimensional (3D)
      rotational imaging with interventional fluoroscopy systems are hampered by the
      fact that not all systems provide individual exposure values for each projection
      image included in the examination. PURPOSE: To investigate the error in resulting
      effective dose introduced by not using individual exposure values for each
      projection image in the dose calculations for 3D rotational imaging with
      interventional fluoroscopy systems. MATERIAL AND METHODS: An interventional
      fluoroscopy system was used to acquire images of two anthropomorphic phantoms.
      Calculations of the effective dose were performed using two different methods: 1,
      using individual exposure values for each projection image; and 2, using the mean
      tube voltage and the total dose-area product (DAP), evenly distributed over a
      selection of projection images. The second method was also tested in hypothetical
      examinations to investigate the effects of worst-case scenarios regarding the
      effect of exposure asymmetry on the error. RESULTS: The error in resulting
      effective dose obtained when simplifying the dose calculations by using Method 2
      instead of Method 1 was within +/-14%. The error increased slightly for the worst
      case scenarios but was still smaller than +/-20%, regardless of anatomical
      region, tube voltage variation, and patient size. CONCLUSION: Given the
      uncertainties associated with the effective dose concept as well as of reported
      DAP values, the present study indicates that dose calculations based on average
      exposure values distributed over a smaller selection of projection angles can
      provide reasonably accurate estimations of the radiation doses from 3D imaging
      using interventional fluoroscopy systems.

PMID- 25852193
TI  - Computed tomography in trauma patients using iterative reconstruction: reducing
      radiation exposure without loss of image quality.
AB  - BACKGROUND: Rising numbers of computed tomography (CT) examinations worldwide
      have led to a focus on dose reduction in the latest developments in CT
      technology. Iterative reconstruction (IR) models bear the potential to
      effectively reduce dose while maintaining adequate image quality. PURPOSE: To
      assess the impact of adaptive statistical iterative reconstruction (ASIR)
      technique on dose reduction and image quality in a dedicated whole body CT (WBCT)
      protocol for trauma patients. MATERIAL AND METHODS: A total of 122 subjects with
      multiple trauma was prospectively included in our study. Subjects who had to
      undergo a WBCT following a severe trauma were randomly assigned to two different
      groups: Group A was examined with an ASIR protocol for the body series (n = 64),
      group B (n = 58) was examined using a standard filtered back projection (FBP)
      protocol. Image quality was assessed both quantitatively by calculating signal-to
      noise ratio (SNR) and contrast-to-noise ratios (CNRs) and qualitatively by two
      observers who evaluated image quality using a 5-point scale system. Applied dose
      was analyzed as CTDIvol (mGy), total DLP (mGyxcm), and effective dose (mSv).
      RESULTS: Applied dose for the body series in group A was about 23% lower than in
      group B (P < 0.05). SNR and CNRs for different tissues were not significantly
      different. Subjective image quality ratings were excellent and showed no
      significant difference, with a high inter-reader agreement. CONCLUSION: ASIR
      contributes to a relevant dose reduction without any loss of image quality in a
      dedicated WBCT protocol for patients with multiple trauma.

PMID- 25852195
TI  - Lack of genetic association between TREM2 and Alzheimer's disease in East Asian
      population: a systematic review and meta-analysis.
AB  - PURPOSE: Large-scale genome-wide association studies have identified TREM2
      variants to be significantly associated with Alzheimer's disease (AD) in
      caucasian population. The goal of this systematic study and meta-analysis was to
      assess the association between Triggering receptor expressed on myeloid cells 2
      (TREM2) variants and AD in East Asian population. METHODS: In this study,
      literatures were searched in PubMed, MEDLINE, EMBASE, and the Cochrane library to
      screen citations from January 1990 to June 2014. Data analysis was done by using
      the Stata 12 software. RESULTS: Twelve studies were considered for analysis. A
      total of 13 535 patients with AD and 22 976 healthy controls were studied. The
      results showed that rs75932628 variant was significantly associated with AD in
      caucasian population (P < .001, odds ratio 1/4 3.17, 95% confidence interval 2.45
      4.09). However, the association was not found in East Asian population.
      CONCLUSION: In our study, we found that TREM2 variant is likely not associated
      with AD in East Asian population.

PMID- 25852196
TI  - Developing peer review.

PMID- 25852197
TI  - Lysophosphatidic acid signalling in development.
AB  - Lysophosphatidic acid (LPA) is a bioactive phospholipid that is present in all
      tissues examined to date. LPA signals extracellularly via cognate G protein
      coupled receptors to mediate cellular processes such as survival, proliferation,
      differentiation, migration, adhesion and morphology. These LPA-influenced
      processes impact many aspects of organismal development. In particular, LPA
      signalling has been shown to affect fertility and reproduction, formation of the
      nervous system, and development of the vasculature. Here and in the accompanying
      poster, we review the developmentally related features of LPA signalling. 

PMID- 25852198
TI  - Dynamic stem cell heterogeneity.
AB  - Recent lineage-tracing studies based on inducible genetic labelling have
      emphasized a crucial role for stochasticity in the maintenance and regeneration
      of cycling adult tissues. These studies have revealed that stem cells are
      frequently lost through differentiation and that this is compensated for by the
      duplication of neighbours, leading to the consolidation of clonal diversity.
      Through the combination of long-term lineage-tracing assays with short-term in
      vivo live imaging, the cellular basis of this stochastic stem cell loss and
      replacement has begun to be resolved. With a focus on mammalian spermatogenesis,
      intestinal maintenance and the hair cycle, we review the role of dynamic
      heterogeneity in the regulation of adult stem cell populations. 

PMID- 25852199
TI  - Glucagon is essential for alpha cell transdifferentiation and beta cell
      neogenesis.
AB  - The interconversion of cell lineages via transdifferentiation is an adaptive mode
      of tissue regeneration and an appealing therapeutic target. However, its clinical
      exploitation is contingent upon the discovery of contextual regulators of cell
      fate acquisition and maintenance. In murine models of diabetes, glucagon
      secreting alpha cells transdifferentiate into insulin-secreting beta cells
      following targeted beta cell depletion, regenerating the form and function of the
      pancreatic islet. However, the molecular triggers of this mode of regeneration
      are unknown. Here, using lineage-tracing assays in a transgenic zebrafish model
      of beta cell ablation, we demonstrate conserved plasticity of alpha cells during
      islet regeneration. In addition, we show that glucagon expression is upregulated
      after injury. Through gene knockdown and rescue approaches, we also find that
      peptides derived from the glucagon gene are necessary for alpha-to-beta cell fate
      switching. Importantly, whereas beta cell neogenesis was stimulated by glucose,
      alpha-to-beta cell conversion was not, suggesting that transdifferentiation is
      not mediated by glucagon/GLP-1 control of hepatic glucose production. Overall,
      this study supports the hypothesis that alpha cells are an endogenous reservoir
      of potential new beta cells. It further reveals that glucagon plays an important
      role in maintaining endocrine cell homeostasis through feedback mechanisms that
      govern cell fate stability. 

PMID- 25852200
TI  - Genome-wide identification of phospho-regulators of Wnt signaling in Drosophila.
AB  - Evolutionarily conserved intercellular signaling pathways regulate embryonic
      development and adult tissue homeostasis in metazoans. The precise control of the
      state and amplitude of signaling pathways is achieved in part through the kinase-
      and phosphatase-mediated reversible phosphorylation of proteins. In this study,
      we performed a genome-wide in vivo RNAi screen for kinases and phosphatases that
      regulate the Wnt pathway under physiological conditions in the Drosophila wing
      disc. Our analyses have identified 54 high-confidence kinases and phosphatases
      capable of modulating the Wnt pathway, including 22 novel regulators. These
      candidates were also assayed for a role in the Notch pathway, and numerous
      phospho-regulators were identified. Additionally, each regulator of the Wnt
      pathway was evaluated in the wing disc for its ability to affect the
      mechanistically similar Hedgehog pathway. We identified 29 dual regulators that
      have the same effect on the Wnt and Hedgehog pathways. As proof of principle, we
      established that Cdc37 and Gilgamesh/CK1gamma inhibit and promote signaling,
      respectively, by functioning at analogous levels of these pathways in both
      Drosophila and mammalian cells. The Wnt and Hedgehog pathways function in tandem
      in multiple developmental contexts, and the identification of several shared
      phospho-regulators serve as potential nodes of control under conditions of
      aberrant signaling and disease. 

PMID- 25852201
TI  - The Rac1 regulator ELMO controls basal body migration and docking in
      multiciliated cells through interaction with Ezrin.

PMID- 25852202
TI  - Japanese Bereaved Family Members' Perspectives of Palliative Care Units and
      Palliative Care: J-HOPE Study Results.
AB  - The study purpose was to understand the perspectives of bereaved family members
      regarding palliative care unit (PCU) and palliative care and to compare
      perceptions of PCU before admission and after bereavement. A cross-sectional
      questionnaire survey was conducted, and the perceptions of 454 and 424 bereaved
      family members were obtained regarding PCU and palliative care, respectively.
      Family members were significantly more likely to have positive perceptions after
      bereavement (ranging from 73% to 80%) compared to before admission (ranging from
      62% to 71%). Bereaved family members who were satisfied with medical care in the
      PCU had a positive perception of the PCU and palliative care after bereavement.
      Respondents younger than 65 years of age were significantly more likely to have
      negative perceptions of PCU and palliative care. 

PMID- 25852203
TI  - Is There a Need for Early Palliative Care in Patients With Life-Limiting
      Illnesses? Interview Study With Patients About Experienced Care Needs From
      Diagnosis Onward.
AB  - The early integration of specialist palliative care has been shown to benefit the
      quality of life of patients with advanced cancer. In order to explore whether
      other seriously ill people and people at even earlier phases would also benefit
      from early palliative care, we conducted 18 qualitative interviews with people
      having cancer, chronic obstructive lung disease, heart failure, or dementia at
      different phases of the illness trajectory about how they experienced care needs
      related to their disease from diagnosis onward. Respondents experienced needs
      within the different domains of palliative care at different stages of the
      illness and different illness types or duration of the illness. This study
      contributes to the understanding of primary care needs of patients for whom
      palliative care (not necessarily specialized palliative care) could be
      beneficial. 

PMID- 25852204
TI  - Improving Diabetes Care for Hospice Patients.
AB  - Although type 2 diabetes guidelines recommend less aggressive glycemic control
      for patients with limited life expectancy, many hospice patients continue their
      glucose-lowering medications, resulting in an increased risk of hypoglycemia.
      Three common reasons for overly tight glycemic control in hospice patients
      include (1) discussions about reducing or stopping chronic medications are
      uncomfortable; (2) many patients and families believe that mild hyperglycemia can
      cause symptoms; and (3) until 2014, Healthcare Information and Data Information
      Set (HEDIS) quality indicators for glycemic control included hospice patients. To
      address these issues, we recommend (1) providers discuss with patients and
      families upon hospice enrollment that diabetes medications can be reduced or
      discontinued as their life-limiting disease progresses; (2) keeping blood glucose
      levels between 200 and 300 mg/dL; and (3) educate providers that HEDIS measures
      now exclude hospice patients. Implementing these recommendations should decrease
      the risk of hypoglycemia in hospice patients and improve their quality of life. 

PMID- 25852205
TI  - Prevalence of and Racial Disparities in Risk Factor Control in Older Adults With
      Diabetes: The Atherosclerosis Risk in Communities Study.
AB  - OBJECTIVE: Controversy surrounds appropriate risk factor targets in older adults
      with diabetes. We evaluated the proportion of older adults with diabetes meeting
      different targets, focusing on possible differences by race, and assessed whether
      demographic and clinical characteristics explained disparities. RESEARCH DESIGN
      AND METHODS: We conducted a cross-sectional study of 5,018 participants aged 67
      90 years (1,574 with and 3,444 without diagnosed diabetes) who attended visit 5
      of the Atherosclerosis Risk in Communities (ARIC) study (2011-2013). Risk factor
      targets were defined using both stringent (and less stringent) goals: hemoglobin
      A1c (HbA1c) <7%, <53 mmol/mol (<8%, <64 mmol/mol); LDL cholesterol (LDL-c) <100
      mg/dL (<130 mg/dL); and blood pressure (BP) <140/90 mmHg (<150/90 mmHg). We used
      Poisson regression to obtain prevalence ratios (PRs). RESULTS: Most older adults
      with diabetes met stringent (and less stringent) targets: 72% (90%) for HbA1c,
      63% (86%) for LDL-c, and 73% (87%) for BP; but only 35% (68%) met all three. A
      higher proportion of whites than blacks met targets, however defined. Among
      people treated for risk factors, racial disparities in prevalence of meeting
      stringent targets persisted even after adjustment: PRs (whites vs. blacks) were
      1.03 (95% CI 0.91, 1.17) for HbA1c, 1.21 (1.09, 1.35) for LDL-c, 1.10 (1.00,
      1.21) for BP, and 1.28 (0.99, 1.66) for all three. Results were similar but
      slightly attenuated using less stringent goals. Black women were less likely than
      white women to meet targets for BP and all three risk factors; this disparity was
      not observed in men. CONCLUSIONS: Black-white disparities in risk factor control
      in older adults with diabetes were not fully explained by demographic or clinical
      characteristics and were greater in women than men. Further study of determinants
      of these disparities is important.

PMID- 25852207
TI  - Prevalence of Prediabetes and Undiagnosed Diabetes in Canada (2007-2011)
      According to Fasting Plasma Glucose and HbA1c Screening Criteria.
AB  - OBJECTIVE: To provide the first population-based estimates of prediabetes and
      undiagnosed type 2 diabetes prevalence in Canada. RESEARCH DESIGN AND METHODS: We
      combined two fasting subsamples of the Canadian Health Measures Survey, which
      were restricted to nonpregnant adults >=20 years of age (N = 3,494). Undiagnosed
      diabetes was defined as not having self-reported type 2 diabetes but having blood
      glucose measures that met Canadian guidelines (i.e., fasting plasma glucose [FPG]
      level of >=7.0 mmol/L or hemoglobin A1c [HbA1c] level of >=6.5% [>=48 mmol/mol]).
      Prediabetes was defined as an FPG level of >=6.1 and <7.0 mmol/L or an HbA1c
      level of >=6.0% and <6.5% (>=42 and <48 mmol/mol). All estimates were weighted
      using survey sampling weights. CIs were calculated with the bootstrap method.
      RESULTS: According to FPG levels, the prevalence of undiagnosed type 2 diabetes
      in Canadian adults was 1.13% (95% CI 0.79, 1.62), contributing to ~20% of total
      type 2 diabetes prevalence (5.62 [95% CI 4.52, 6.95]). Compared with FPG levels,
      the undiagnosed prevalence was greater using HbA1c level as a criterion (3.09%
      [95% CI 1.97, 4.81]), ~41% of the total number of cases of diabetes (7.55 [95% CI
      5.98, 9.49]). The HbA1c-only criterion resulted in a threefold increase in
      prediabetes prevalence overall and a sixfold increase among females (FPG 2.22%,
      HbA1c 13.31%). Screening based on FPG only identified older undiagnosed case
      patients, with a mean age of 58.7 years (95% CI 59.9, 63.4). Similarly, using
      HbA1c identified younger individuals with prediabetes, with reduced BMI and waist
      circumference compared with FPG levels. CONCLUSIONS: In this first study of a
      nationally representative sample with biospecimen measures, we found that the
      prevalence of undiagnosed type 2 diabetes and prediabetes was significantly
      higher using HbA1c levels compared with FPG levels. Further evaluation is needed
      to fully assess the impact of using the HbA1c criterion.

PMID- 25852206
TI  - Effects of Dietary n-3 Fatty Acids on Hepatic and Peripheral Insulin Sensitivity
      in Insulin-Resistant Humans.
AB  - OBJECTIVE: Dietary n-3 polyunsaturated fatty acids, including eicosapentaenoic
      acid (EPA) and docosahexaenoic acid (DHA), prevent insulin resistance and
      stimulate mitochondrial biogenesis in rodents, but the findings of translational
      studies in humans are thus far ambiguous. The aim of this study was to evaluate
      the influence of EPA and DHA on insulin sensitivity, insulin secretion, and
      muscle mitochondrial function in insulin-resistant, nondiabetic humans using a
      robust study design and gold-standard measurements. RESEARCH DESIGN AND METHODS:
      Thirty-one insulin-resistant adults received 3.9 g/day EPA+DHA or placebo for 6
      months in a randomized double-blind study. Hyperinsulinemic-euglycemic clamp with
      somatostatin was used to assess hepatic and peripheral insulin sensitivity.
      Postprandial glucose disposal and insulin secretion were measured after a meal.
      Measurements were performed at baseline and after 6 months of treatment.
      Abdominal fat distribution was evaluated by MRI. Muscle oxidative capacity was
      measured in isolated mitochondria using high-resolution respirometry and
      noninvasively by magnetic resonance spectroscopy. RESULTS: Compared with placebo,
      EPA+DHA did not alter peripheral insulin sensitivity, postprandial glucose
      disposal, or insulin secretion. Hepatic insulin sensitivity, determined from the
      suppression of endogenous glucose production by insulin, exhibited a small but
      significant improvement with EPA+DHA compared with placebo. Muscle mitochondrial
      function was unchanged by EPA+DHA or placebo. CONCLUSIONS: This study
      demonstrates that dietary EPA+DHA does not improve peripheral glucose disposal,
      insulin secretion, or skeletal muscle mitochondrial function in insulin-resistant
      nondiabetic humans. There was a modest improvement in hepatic insulin sensitivity
      with EPA+DHA, but this was not associated with any improvements in clinically
      meaningful outcomes.

PMID- 25852208
TI  - Dapagliflozin's Effects on Glycemia and Cardiovascular Risk Factors in High-Risk
      Patients With Type 2 Diabetes: A 24-Week, Multicenter, Randomized, Double-Blind,
      Placebo-Controlled Study With a 28-Week Extension.
AB  - OBJECTIVE: To assess the efficacy and safety of dapagliflozin, a selective sodium
      glucose cotransporter 2 inhibitor, compared with placebo in patients with type 2
      diabetes (T2D), documented pre-existing cardiovascular disease (CVD), and a
      history of hypertension. RESEARCH DESIGN AND METHODS: Patients (N = 922) were
      randomized to receive 10 mg dapagliflozin or placebo in a double-blind trial for
      24 weeks, followed by a 28-week extension period. In patients receiving insulin,
      the insulin dose was reduced by 25% at randomization. Patients were stratified by
      age, insulin use, and time from the most recent qualifying cardiovascular (CV)
      event. Co-primary end points were a change from baseline in hemoglobin A1c
      (HbA1c) and the proportion of patients achieving a combined reduction in HbA1c of
      >=0.5% (5.5 mmol/mol), body weight (BW) of >=3%, and systolic blood pressure
      (SBP) of >=3 mmHg. RESULTS: At 24 weeks, dapagliflozin significantly reduced
      HbA1c (-0.38% [-4.2 mmol/mol]) from baseline (8.18%) compared with a slight
      increase with placebo from baseline (8.08%) (0.08% [0.9 mmol/mol]). Significantly
      more patients met the three-item end point with treatment with dapagliflozin than
      with placebo (11.7% vs. 0.9%, respectively). Changes were maintained over 52
      weeks. Although ~42% of patients were >=65 years old, similar results were
      observed in both age-stratified groups. Serious adverse events, hypoglycemia,
      urinary tract infections, and cardiac disorders were similar between groups.
      Adverse events of hypotension, dehydration, hypovolemia, genital infection, and
      renal failure or impairment occurred more often with dapagliflozin treatment.
      CONCLUSIONS: In this study that evaluated T2D patients who were at high risk for
      future CVD events, dapagliflozin administration had significantly greater effects
      in reducing HbA1c, BW, and SBP, without adversely impacting CV safety when
      compared with placebo treatment.

PMID- 25852209
TI  - Genetic Predisposition to Central Obesity and Risk of Type 2 Diabetes: Two
      Independent Cohort Studies.
AB  - OBJECTIVE: Abdominal obesity is a major risk factor for type 2 diabetes (T2D). We
      aimed to examine the association between the genetic predisposition to central
      obesity, assessed by the waist-to-hip ratio (WHR) genetic score, and T2D risk.
      RESEARCH DESIGN AND METHODS: The current study included 2,591 participants with
      T2D and 3,052 participants without T2D of European ancestry from the Nurses'
      Health Study (NHS) and the Health Professionals Follow-up Study (HPFS). Genetic
      predisposition to central obesity was estimated using a genetic score based on 14
      established loci for the WHR. RESULTS: We found that the central obesity genetic
      score was linearly related to higher T2D risk. Results were similar in the NHS
      (women) and HPFS (men). In combined results, each point of the central obesity
      genetic score was associated with an odds ratio (OR) of 1.04 (95% CI 1.01-1.07)
      for developing T2D, and the OR was 1.24 (1.03-1.45) when comparing extreme
      quartiles of the genetic score after multivariate adjustment. CONCLUSIONS: The
      data indicate that genetic predisposition to central obesity is associated with
      higher T2D risk. This association is mediated by central obesity.

PMID- 25852210
TI  - Longitudinal Association Between Endothelial Dysfunction, Inflammation, and
      Clotting Biomarkers With Subclinical Atherosclerosis in Type 1 Diabetes: An
      Evaluation of the DCCT/EDIC Cohort.
AB  - OBJECTIVE: There is considerable interest in identifying biomarkers that predict
      high risk for the development of macrovascular complications in patients with
      diabetes. Therefore, the longitudinal association between subclinical
      atherosclerosis as measured by internal carotid artery intima-media thickness
      (IMT) and acute-phase reactants, cytokines/adipokines, thrombosis, and adhesion
      molecules was examined. RESEARCH DESIGN AND METHODS: Biomarkers were measured at
      four time points over 20 years in 886 DCCT/EDIC participants with type 1
      diabetes. Four composite scores were created by combining z scores generated from
      within the data set of individual biomarkers: acute-phase reactants (fibrinogen,
      C-reactive protein), thrombosis (fibrinogen, active and total plasminogen
      activator inhibitor [PAI]-1), cytokines/adipokines (tumor necrosis factor
      receptor-1 and -2, active and total PAI-1, IL-6), and endothelial dysfunction
      (soluble intracellular adhesion molecule-1, soluble vascular cell adhesion
      molecule-1, and soluble E-selectin). Internal carotid IMT was measured at EDIC
      years 1, 6, and 12, with elevated IMT defined at each time point as being in the
      upper quintile of its distribution. RESULTS: Logistic regression models indicate
      that while individual biomarkers were not predictive of or associated with
      subclinical atherosclerosis, composite scores of acute-phase reactants (odds
      ratio [OR] 2.78 [95% CI 1.42, 5.42]), thrombolytic factors (OR 2.83 [95% CI 1.45,
      5.52]), and cytokines/adipokines (OR 2.83 [95% CI 1.48, 5.41]) measured at our
      final time point EDIC years 8-11 were associated with higher levels of
      atherosclerosis at EDIC year 12, but findings were not consistent at early time
      points. The endothelial dysfunction score was not appreciably predictive of or
      associated with subclinical atherosclerosis at any of the time points measured.
      CONCLUSIONS: The pathophysiologic relationship between higher biomarker levels
      and progression of subclinical atherosclerosis remains unclear.

PMID- 25852211
TI  - Platelet-to-Lymphocyte Ratio Predicts Contrast-Induced Nephropathy in Patients
      With Non-ST-Segment Elevation Acute Coronary Syndrome.
AB  - We assessed the relation between platelet-to-lymphocyte ratio (PLR) on admission
      and contrast-induced nephropathy (CIN) in patients with non-ST-segment elevation
      acute coronary syndrome (NSTE-ACS). A total of 488 patients with NSTE-ACS who
      underwent urgent coronary angiography were enrolled. Levels of PLR and creatinine
      were measured before angiography and at 72 hours after angiography. Patients were
      divided into 2 groups, namely, the CIN group, 80 patients (16.3%; age 65.3 +/-
      12.5years; 66.7% men) and the non-CIN group, 408 patients (83.7%; age 61.2 +/-
      12.3 years; 72.5% men). Patients in the CIN group had significantly higher PLR
      than those in the non-CIN group (152.9 +/- 99.6 vs 120.4 +/- 66.1, P < .001). In
      logistic regression analysis, PLR (odds ratio [OR] 1.004, 95% confidence interval
      [CI] 1.001-1.007, P = .02), diabetes mellitus (OR 1.75, 95% CI 1.02-2.98, P =
      .03), and ST-segment depression on admission electrocardiogram (OR 1.68, 95% CI
      1.00-2.81, P = .04) were independent predictors of CIN. The PLR was an
      independent predictor of CIN after angiography in patients with NSTE-ACS. 

PMID- 25852212
TI  - Importance of Uric Acid Levels and Comorbidities Affecting Renal Function.

PMID- 25852213
TI  - Microbiome Disturbances and Autism Spectrum Disorders.
AB  - Autism spectrum disorders (ASDs) are considered a heterogenous set of
      neurobehavioral diseases, with the rates of diagnosis dramatically increasing in
      the past few decades. As genetics alone does not explain the underlying cause in
      many cases, attention has turned to environmental factors as potential
      etiological agents. Gastrointestinal disorders are a common comorbidity in ASD
      patients. It was thus hypothesized that a gut-brain link may account for some
      autistic cases. With the characterization of the human microbiome, this concept
      has been expanded to include the microbiota-gut-brain axis. There are mounting
      reports in animal models and human epidemiologic studies linking disruptive
      alterations in the gut microbiota or dysbiosis and ASD symptomology. In this
      review, we will explore the current evidence that gut dysbiosis in animal models
      and ASD patients correlates with disease risk and severity. The studies to date
      have surveyed how gut microbiome changes may affect these neurobehavioral
      disorders. However, we harbor other microbiomes in the body that might impact
      brain function. We will consider microbial colonies residing in the oral cavity,
      vagina, and the most recently discovered one in the placenta. Based on the
      premise that gut microbiota alterations may be causative agents in ASD, several
      therapeutic options have been tested, such as diet modulations, prebiotics,
      probiotics, synbiotics, postbiotics, antibiotics, fecal transplantation, and
      activated charcoal. The potential benefits of these therapies will be considered.
      Finally, the possible mechanisms by which changes in the gut bacterial
      communities may result in ASD and related neurobehavioral disorders will be
      examined.

PMID- 25852214
TI  - In situ simulation as a quality improvement initiative.
AB  - Simulation-based learning has gained recent recognition as a means of improving
      patient safety. In situ simulation, that is conducting simulation training in
      actual clinical environment, is a novel approach to detecting deficiencies in
      healthcare systems, termed as latent safety threats (LSTs). We implemented in
      situ simulation training as a quality improvement initiative and were able to
      detect several LSTs, thus improving patient safety. 

PMID- 25852215
TI  - A rare case of left internal mammary artery disease before bypass surgery.

PMID- 25852216
TI  - Cardiovascular morbidity and mortality related to orthostatic hypotension: a meta
      analysis of prospective observational studies.
AB  - BACKGROUND: Whether orthostatic hypotension (OH) is a risk factor for
      cardiovascular morbidity and death is uncertain. Currently available evidence
      derives from non-homogeneous and partly ambiguous studies. OBJECTIVE: We aimed at
      assessing the relationship between OH and death or major adverse cardiac and
      cerebrovascular events (MACCEs) by integrating results of previous studies.
      METHODS: We performed a meta-analysis of prospective observational studies
      reporting on the association between prevalent OH, mortality, and incident MACCE,
      published from 1966 through 2013. Mantel-Haenszel pooled estimates of relative
      risk (RR) and 95% confidence intervals (CIs) for all-cause death were assessed as
      the primary endpoint at the longest follow-up; incident coronary heart disease
      (CHD), heart failure (HF), and stroke were assessed as secondary endpoints. We
      also performed post hoc subgroup analyses stratified by age and a meta-regression
      analysis. RESULTS: We identified a total of 13 studies, including an overall
      population of 121 913 patients, with a median follow-up of 6 years. Compared with
      the absence of OH, the occurrence of OH was associated with a significantly
      increased risk of all-cause death (RR 1.50; 95% CI 1.24-1.81), incident CHD (RR
      1.41; 95% CI 1.22-1.63), HF (RR 2.25; 95% CI 1.52-3.33), and stroke (RR 1.64; 95%
      CI 1.13-2.37). When analysed according to age, pooled estimates of RR (95% CI)
      for all-cause death were 1.78 (1.25-2.52) for patients <65 years old, and 1.26
      (0.99-1.62) in the older subgroup. CONCLUSION: Orthostatic hypotension is
      associated with a significantly increased risk of all-cause death, incident CHD,
      HF, and stroke.

PMID- 25852217
TI  - When everything is not everywhere but species evolve: an alternative method to
      model adaptive properties of marine ecosystems.
AB  - The functional and taxonomic biogeography of marine microbial systems reflects
      the current state of an evolving system. Current models of marine microbial
      systems and biogeochemical cycles do not reflect this fundamental organizing
      principle. Here, we investigate the evolutionary adaptive potential of marine
      microbial systems under environmental change and introduce explicit Darwinian
      adaptation into an ocean modelling framework, simulating evolving phytoplankton
      communities in space and time. To this end, we adopt tools from adaptive dynamics
      theory, evaluating the fitness of invading mutants over annual timescales,
      replacing the resident if a fitter mutant arises. Using the evolutionary
      framework, we examine how community assembly, specifically the emergence of
      phytoplankton cell size diversity, reflects the combined effects of bottom-up and
      top-down controls. When compared with a species-selection approach, based on the
      paradigm that "Everything is everywhere, but the environment selects", we show
      that (i) the selected optimal trait values are similar; (ii) the patterns
      emerging from the adaptive model are more robust, but (iii) the two methods lead
      to different predictions in terms of emergent diversity. We demonstrate that
      explicitly evolutionary approaches to modelling marine microbial populations and
      functionality are feasible and practical in time-varying, space-resolving
      settings and provide a new tool for exploring evolutionary interactions on a
      range of timescales in the ocean.

PMID- 25852218
TI  - Serum creatinine level: a supplemental index to distinguish Duchenne muscular
      dystrophy from Becker muscular dystrophy.
AB  - BACKGROUND: To improve assessment of dystrophinopathy, the aim of this study was
      to identify whether serum creatinine (Crn) level reflects disease severity.
      METHODS: Biochemical, Vignos score, and genetic data were collected on 212 boys
      with dystrophinopathy. RESULTS: Serum Crn level had a strong inverse correlation
      with Vignos score by simple correlation (r = -0.793) and partial correlation
      analysis after adjustment for age, height, and weight (r = -0.791; both P <
      0.01). Serum Crn level was significantly higher in patients with in-frame than
      out-of-frame mutations (Z = -4.716,  P < 0.01) and in Becker muscular dystrophy
      (BMD) patients than Duchenne muscular dystrophy (DMD) patients at ages 4, 5, 7,
      and 9 yr (all P < 0.0125). After adjusting for age, height, and weight, BMD
      patients still had a significantly higher serum Crn level than DMD patients (beta
      = 7.140,  t = 6.277,  P < 0.01). CONCLUSIONS: Serum Crn level reflected disease
      severity and may serve as a supplemental index to distinguish DMD from BMD in
      clinical practice.

PMID- 25852219
TI  - Vascular effects of advanced glycation end-products: content of
      immunohistochemically detected AGEs in radial artery samples as a predictor for
      arterial calcification and cardiovascular risk in asymptomatic patients with
      chronic kidney disease.
AB  - OBJECTIVES: Our aim was to determine whether vascular deposition of advanced
      glycation end-products (AGEs) is associated with arterial calcification and
      cardiovascular mortality in chronic kidney disease (CKD) patients and to assess
      the relationships between vascular content of AGEs and selected clinical and
      biochemical parameters. MATERIALS AND METHODS: The study comprised 54 CKD
      patients (33 hemodialyzed, 21 predialyzed). Examined parameters included BMI,
      incidence of diabetes, plasma fasting glucose, AGEs, soluble receptor for AGEs
      and 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging, serum C-reactive protein
      (hsCRP), plasminogen activator inhibitor-1 (PAI-1), and fetuin-A. Fragments of
      radial artery obtained during creation of hemodialysis access were stained for
      calcifications using alizarin red. AGEs deposits were identified
      immunohistochemically and their relative content was quantified. RESULTS:
      Vascular content of AGEs was positively correlated with BMI, hsCRP, fetuin-A, PAI
      1, and DPPH scavenging in simple regression; only fetuin-A was an independent
      predictor in multiple regression. There was a significant positive trend in the
      intensity of AGEs immunostaining among patients with grades 1, 2, and 3
      calcifications. AGEs immunostaining intensity predicted 3-year cardiovascular
      mortality irrespective of patient's age. CONCLUSIONS: The present study
      demonstrates an involvement of AGEs in the development of medial arterial
      calcification and the impact of arterial AGE deposition on cardiovascular
      mortality in CKD patients.

PMID- 25852220
TI  - The apolipoprotein B/apolipoprotein A-I ratio as a potential marker of plasma
      atherogenicity.
AB  - BACKGROUND: The apolipoprotein (apo) B/apoA-I ratio represents the balance
      between apoB-rich atherogenic particles and apoA-I-rich antiatherogenic
      particles, and this ratio is considered to be a marker of cardiovascular risk.
      Although many studies have demonstrated the importance of the apoB/apoA-I ratio
      in predicting the presence or absence of cardiovascular disease, less is known
      about apoB/apoA-I ratio as a marker of plasma atherogenicity. METHODS: A total of
      157 normolipidemic men aged 20-59 years were included in the study. The plasma
      levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein
      cholesterol (HDL-C), apoA-I, apoB, and apoE were determined after a 12 h fasting
      period. RESULTS: The median of the apoB/apoA-I ratio in the studied
      normolipidemic subjects was 0.52, with values ranging from 0.19 to 2.60. The
      percentage of subjects with the apoB/apoA-I ratio exceeding 0.9 (the accepted
      risk value of cardiovascular disease) was 19.1%. The subjects with apoB/apoA
      I>0.9 were characterized by higher TG levels and atherogenic index of plasma
      (AIP) and lower values of ratio of low-density lipoprotein cholesterol (LDL-C) to
      apoB (LDL-C/apoB) and apoE levels compared with men with apoB/apoA-I<0.9.
      CONCLUSION: Despite normolipidemia, the subjects with the unfavorable apoB/apoA-I
      ratio had more atherogenic lipid profile.

PMID- 25852221
TI  - Procalcitonin levels in gram-positive, gram-negative, and fungal bloodstream
      infections.
AB  - Procalcitonin (PCT) can discriminate bacterial from viral systemic infections and
      true bacteremia from contaminated blood cultures. The aim of this study was to
      evaluate PCT diagnostic accuracy in discriminating Gram-positive, Gram-negative,
      and fungal bloodstream infections. A total of 1,949 samples from patients with
      suspected bloodstream infections were included in the study. Median PCT value in
      Gram-negative (13.8 ng/mL, interquartile range (IQR) 3.4-44.1) bacteremias was
      significantly higher than in Gram-positive (2.1 ng/mL, IQR 0.6-7.6) or fungal
      (0.5 ng/mL, IQR 0.4-1) infections (P < 0.0001). Receiver operating characteristic
      analysis showed an area under the curve (AUC) for PCT of 0.765 (95% CI 0.725
      0.805, P < 0.0001) in discriminating Gram-negatives from Gram-positives at the
      best cut-off value of 10.8 ng/mL and an AUC of 0.944 (95% CI 0.919-0.969, P <
      0.0001) in discriminating Gram-negatives from fungi at the best cut-off of 1.6
      ng/mL. Additional results showed a significant difference in median PCT values
      between Enterobacteriaceae and nonfermentative Gram-negative bacteria (17.1
      ng/mL, IQR 5.9-48.5 versus 3.5 ng/mL, IQR 0.8-21.5; P < 0.0001). This study
      suggests that PCT may be of value to distinguish Gram-negative from Gram-positive
      and fungal bloodstream infections. Nevertheless, its utility to predict different
      microorganisms needs to be assessed in further studies.

PMID- 25852222
TI  - Immunohistochemical expression of nuclear factor erythroid-2-related factor 2 and
      heme oxygenase 1 in normal bovine lung and bovine lung infected with Mannheimia
      haemolytica.
AB  - Mannheimia haemolytica is an important cause of pneumonia in feedlot cattle.
      Nuclear factor erythroid-2-related factor 2 (Nrf2) is a redox-sensitive
      transcription factor responsible for the induction of antioxidant enzymes, such
      as heme oxygenase 1 (HO-1), within the lung. The expression of Nrf2 and HO-1 was
      immunohistochemically evaluated in 4 calves 24 h after experimental infection
      with M. haemolytica. Calves receiving normal saline served as controls. In the
      infected lungs, cytoplasmic Nrf2 expression was high in macrophages and
      bronchioles and low in alveolar epithelium, whereas nuclear expression was high
      in endothelial cells, macrophages, and bronchioles and lowest in alveolar
      epithelium. Normal lung samples displayed only faint Nrf2 cytoplasmic staining
      within bronchiolar epithelium. Expression of HO-1 was detected within the
      cytoplasm of macrophages and bronchiolar epithelial cells in all infected lung
      samples, whereas normal lungs displayed only weak cytoplasmic staining in
      bronchiolar epithelial cells. These findings suggest that bronchiolar epithelial
      cells and macrophages up-regulate Nrf2 expression early in the course of
      infection, which results in increased expression of HO-1 within these cells. 

PMID- 25852223
TI  - Avian reovirus replication in mononuclear phagocytes in chicken footpad and
      spleen after footpad inoculation.
AB  - Circulating monocytes and tissue macrophages were suggested to be susceptible to
      avian reovirus (ARV) infection. To determine if ARV infects and replicates in
      mononuclear phagocytes (KUL01-positive cells), we infected 3-day-old specific
      pathogen-free chickens with ARV strain 2408 by inoculation of the left footpad.
      The left footpads and spleens were collected for analysis at 1.5 and 2.5 d after
      inoculation. Replication of ARV in the footpad and spleen was demonstrated by
      detection of the viral protein sigmaNS using immunohistochemical testing and
      viral S1 RNA expression by real-time quantitative polymerase chain reaction
      (qPCR). Furthermore, immunofluorescent double-staining assay of cytocentrifuged
      cells and cryosections of the footpad and spleen for the viral protein sigmaNS
      and the surface marker recognized by monoclonal antibody (MAb) KUL01 indicated
      that KUL01-positive cells costained with MAb H1E1, which recognizes ARV protein
      sigmaNS. In addition, more ARV S1 RNA was measured by qPCR in the KUL01-positive
      cell samples prepared from the footpad or spleen 1.5 d after inoculation compared
      with non-KUL01-positive cell samples. The amounts of ARV S1 RNA in the spleen
      were significantly lower (P < 0.05) than the amounts in the footpad 1.5 d after
      inoculation. The results suggest that ARV infects mononuclear phagocytes and then
      replicates within these cells before migrating to the spleen, where it infects
      and replicates in KUL01-positive cells. 

PMID- 25852224
TI  - The anesthetic interaction of propofol and sevoflurane on the minimum alveolar
      concentration preventing motor movement (MACNM) in dogs.
AB  - The objective of this study was to determine the effects of propofol on the
      minimum alveolar concentration of sevoflurane needed to prevent motor movement
      (MAC(NM)) in dogs subjected to a noxious stimulus using randomized crossover
      design. Six, healthy, adult beagles (9.2 +/- 1.3 kg) were used. Dogs were
      anesthetized with sevoflurane on 3 occasions, at weekly intervals, and baseline
      MAC(NM) (MAC(NM-B)) was determined on each occasion. Propofol treatments were
      administered as loading dose (LD) and constant rate infusion (CRI) as follows:
      Treatment 1 (T1) was 2 mg/kg body weight (BW) and 4.5 mg/kg BW per hour; T2 was 4
      mg/kg BW and 9 mg/kg BW per hour; T3 was 8 mg/kg BW and 18 mg/kg BW per hour,
      respectively. Treatment MAC(NM) (MAC(NM-T)) determination was initiated 60 min
      after the start of the CRI. Two venous blood samples were collected and combined
      at each MAC(NM-T) determination for measurement of blood propofol concentration
      using high-performance liquid chromatography method (HPLC). Data were analyzed
      using a mixed-model ANOVA and are presented as least square means (LSM) +/-
      standard error of means (SEM). Propofol infusions in the range of 4.5 to 18 mg/kg
      BW per hour resulted in mean blood concentrations between 1.3 and 4.4 MUg/mL, and
      decreased (P < 0.05) sevoflurane MAC(NM) in a concentration-dependent manner. The
      percentage decrease in MAC(NM) was 20.5%, 43.0%, and 68.3%, with corresponding
      blood propofol concentrations of 1.3 +/- 0.3 MUg/mL, 2.5 +/- 0.3 MUg/mL, and 4.4
      +/- 0.3 MUg/mL, for T1, T2, and T3, respectively. Venous blood propofol
      concentrations were strongly correlated (r = 0.855, P < 0.0001) with the decrease
      in MAC(NM). In dogs, propofol decreased the sevoflurane MAC(NM) in a
      concentration-dependent manner.

PMID- 25852225
TI  - Osteogenic potential of sorted equine mesenchymal stem cell subpopulations.
AB  - The objectives of this study were to use non-equilibrium gravitational field-flow
      fractionation (GrFFF), an immunotag-less method of sorting mesenchymal stem cells
      (MSCs), to sort equine muscle tissue-derived mesenchymal stem cells (MMSCs) and
      bone marrow-derived mesenchymal stem cells (BMSC) into subpopulations and to
      carry out assays in order to compare their osteogenic capabilities. Cells from 1
      young adult horse were isolated from left semitendinosus muscle tissue and from
      bone marrow aspirates of the fourth and fifth sternebrae. Aliquots of 800 * 10(3)
      MSCs from each tissue source were sorted into 5 fractions using non-equilibrium
      GrFFF (GrFFF proprietary system). Pooled fractions were cultured and expanded for
      use in osteogenic assays, including flow cytometry, histochemistry, bone nodule
      assays, and real-time quantitative polymerase chain reaction (qPCR) for gene
      expression of osteocalcin (OCN), RUNX2, and osterix. Equine MMSCs and BMSCs were
      consistently sorted into 5 fractions that remained viable for use in further
      osteogenic assays. Statistical analysis confirmed strongly significant
      upregulation of OCN, RUNX2, and osterix for the BMSC fraction 4 with P < 0.00001.
      Flow cytometry revealed different cell size and granularity for BMSC fraction 4
      and MMSC fraction 2 compared to unsorted controls and other fractions.
      Histochemisty and bone nodule assays revealed positive staining nodules without
      differences in average nodule area, perimeter, or stain intensity between tissues
      or fractions. As there are different subpopulations of MSCs with different
      osteogenic capacities within equine muscle- and bone marrow-derived sources,
      these differences must be taken into account when using equine stem cell therapy
      to induce bone healing in veterinary medicine. 

PMID- 25852226
TI  - The effect of dystocia on physiological and behavioral characteristics related to
      vitality and passive transfer of immunoglobulins in newborn Holstein calves.
AB  - The objective of this study was to examine the effect of calving difficulty or
      dystocia on the vitality of newborn calves and its association with blood pH, the
      apparent efficiency of immunoglobulin G (IgG) absorption (AEA), and weight gain.
      A total of 45 calving events (N = 48 calves) were monitored from the first sight
      of fetal membranes. All calves were assessed at the time of first attaining
      sternal recumbency (SR), at 2 and 24 h, and at 7 and 14 d of age. Measurements
      included time to SR, rectal temperature, respiration and heart rate, analysis of
      blood gases and other blood measures, suckling response, time to standing,
      passive transfer of IgG, and weight gain. Calves were separated from their dam 2
      h after birth and fed a commercial colostrum replacer containing 180 g of IgG by
      esophageal tube feeder. Calves born following dystocia had lower venous blood pH
      and took longer to attain SR and attempt to stand than those born unassisted.
      Duration of calving interacted with the number of people required to extract the
      calf by pulling as a significant predictor of pH at SR. No association was found
      between pH at SR and AEA. However, reduced AEA was found in calves that were
      female and in calves that did not achieve SR within 15 min of birth. A longer
      calving duration, being born in July or August rather than June, and a shorter
      time spent standing in the first 2 d of life were significantly associated with
      reduced weight gain to 14 d. It was concluded that factors at calving impact the
      physiology, vitality, and subsequent weight gain of newborn calves. 

PMID- 25852227
TI  - Identification of Escherichia coli F4ac-binding proteins in porcine milk fat
      globule membrane.
AB  - F4ac-positive enterotoxigenic Escherichia coli (ETEC) must attach to the
      intestinal mucosa to cause diarrhea in piglets. Prevention of bacterial
      attachment to the intestinal mucosa is the most effective defense against ETEC
      induced diarrhea. Porcine milk fat globule membranes (MFGM) were shown to be able
      to inhibit attachment of ETEC to the intestinal brush border; however, the
      specific components of porcine MFGM that inhibited attachment of ETEC to
      enterocytes were not identified. Accordingly, the purpose of this study was to
      identify F4ac-binding MFGM proteins by overlay Western blot and affinity
      chromatography. The proteome of porcine MFGM was characterized and the following
      F4ac-binding proteins were detected by overlay Western blot and affinity
      chromatography: lactadherin, butyrophilin, adipophilin, acyl-CoA synthetase 3,
      and fatty acid-binding protein 3. The biological function of these proteins was
      not investigated but it is possible that their interaction with F4ac fimbria
      interferes with bacterial attachment and colonization. 

PMID- 25852228
TI  - Staphylococcus spp., Streptococcus canis, and Arcanobacterium phocae of healthy
      Canadian farmed mink and mink with pododermatitis.
AB  - Pododermatitis is a disease of concern for mink breeders in Canada and worldwide,
      as it causes discomfort and lowers the breeding rates on farms affected by the
      disease. Unfortunately, the etiology and pathogenesis of pododermatitis are still
      unknown. In this study, we compared Staphylococcus spp. and Streptococcus canis
      isolates from healthy mink with isolates from animals with pododermatitis on 2
      farms in Ontario. Almost all hemolytic Staphylococcus spp. isolated were shown to
      be Staphylococcus delphini Group A by 16S ribosomal ribonucleic acid (rRNA)
      sequence analysis and polymerase chain reaction (PCR). Pulsed-field gel
      electrophoresis (PFGE) did not reveal any S. delphini or S. canis clonal lineages
      specifically associated with pododermatitis, which suggests that these bacteria
      do not act as primary pathogens, but does not dismiss their potential roles as
      opportunistic pathogens. While S. delphini and S. canis were the most prevalent
      bacterial pathogens in mink pododermatitis, they were also present in samples
      from healthy mink. Arcanobacterium phocae is occasionally isolated from
      pododermatitis cases, but is difficult to recover with conventional culture
      methods due to its slow growth. A quantitative real-time PCR was developed for
      the detection of A. phocae and was tested on 138 samples of footpad tissues from
      14 farms. The bacterium was detected only in pododermatitis-endemic farms in
      Canada and was at higher concentrations in tissues from infected footpads than in
      healthy tissues. This finding suggests that A. phocae is involved in the
      pathogenesis of pododermatitis. 

PMID- 25852229
TI  - Assessment of a correlation between Canine Atopic Dermatitis Extent and Severity
      Index (CADESI-03) and selected biophysical skin measures (skin hydration, pH, and
      erythema intensity) in dogs with naturally occurring atopic dermatitis.
AB  - Atopic dermatitis is a common allergic skin disease in dogs. The aim of this
      study was to examine the possibility of a correlation between biophysical skin
      variables: skin hydration (SH), skin pH, and erythema intensity measured in 10
      different body regions and both total Canine Atopic Dermatitis Extent and
      Severity Index (CADESI-03) and CADESI measured in a given region (CADESI L). The
      study was conducted using 33 dogs with atopic dermatitis. The assessment of the
      biophysical variables was done in 10 body regions: the lumbar region, right
      axillary fossa, right inguinal region, ventral abdominal region, right lateral
      thorax region, internal surface of the auricle, interdigital region of right
      forelimb, cheek, bridge of nose, and lateral site of antebrachum. Positive
      correlations were found between SH and CADESI L for the following regions: the
      inguinal region (r = 0.73) and the interdigital region (r = 0.82), as well as
      between total CADESI and SH on digital region (r = 0.52). Also, positive
      correlations were reported for skin pH and CADESI L in the lumbar region (r =
      0.57), the right lateral thorax region (r = 0.40), and the lateral antebrachum (r
      = 0.35). Positive correlations were found in the interdigital region between
      erythema intensity and the total CADESI-03 (r = 0.60) as well as the CADESI L (r
      = 0.7). The results obtained suggest that it may be possible to use skin
      hydration, pH, and erythema intensity to assess the severity of skin lesion but
      positive correlation was only found in < 13.3% of possible correlations and usage
      of these measures in dogs is limited. 

PMID- 25852230
TI  - Role of the capsular polysaccharide as a virulence factor for Streptococcus suis
      serotype 14.
AB  - Streptococcus suis is an important swine pathogen and a zoonotic agent causing
      meningitis and septicemia. Although serotype 2 is the most virulent type,
      serotype 14 is emerging, and understanding of its pathogenesis is limited. To
      study the role of the capsular polysaccharide (CPS) of serotype 14 as a virulence
      factor, we constructed knockout mutants devoid of either cps14B, a highly
      conserved regulatory gene, or neu14C, a gene coding for uridine diphospho-N
      acetylglucosamine 2-epimerase, which is involved in sialic acid synthesis. The
      mutants showed total loss of the CPS with coagglutination assays and electron
      microscopy. Phagocytosis assays showed high susceptibility of mutant Deltacps14B.
      An in vivo murine model was used to demonstrate attenuated virulence of this non
      encapsulated mutant. Despite the difference in the CPS composition of different
      serotypes, this study has demonstrated for the first time that the CPS of a
      serotype other than 2 is also an important antiphagocytic factor and a critical
      virulence factor. 

PMID- 25852231
TI  - Sequence and phylogenetic analysis of M-class genome segments of novel duck
      reovirus NP03.
AB  - We report the sequence and phylogenetic analysis of the entire M1, M2, and M3
      genome segments of the novel duck reovirus (NDRV) NP03. Alignment between the
      newly determined nucleotide sequences as well as their deduced amino acid
      sequences and the published sequences of avian reovirus (ARV) was carried out
      with DNASTAR software. Sequence comparison showed that the M2 gene had the most
      variability among the M-class genes of DRV. Phylogenetic analysis of the M-class
      genes of ARV strains revealed different lineages and clusters within DRVs. The 5
      NDRV strains used in this study fall into a well-supported lineage that includes
      chicken ARV strains, whereas Muscovy DRV (MDRV) strains are separate from NDRV
      strains and form a distinct genetic lineage in the M2 gene tree. However, the
      MDRV and NDRV strains are closely related and located in a common lineage in the
      M1 and M3 gene trees, respectively. 

PMID- 25852232
TI  - Relationship between vaginal mucus conductivity and time of ovulation in weaned
      sows.
AB  - This study investigated whether changes in the vaginal electrical resistance
      (VER) of vaginal mucus of weaned sows during the first 7 d post-weaning are
      associated with time of ovulation. Time of ovulation was determined by ovarian
      ultrasound carried out from 91 to 146 h after weaning and at different seasons.
      Vaginal electrical resistance was measured at 20, 44, 68, 91, 96, 102, 115, 120,
      126, 140, 146, and 164 h post-weaning and was found to decrease between 120 h and
      31 h before ovulation and then increase until 40 to 50 h after ovulation.
      Duration and timing of the nadir was affected by the season (P < 0.01). Estrus
      was observed from day 4 after the lowest VER values. Ovulation occurred between
      late day 5 and late day 6, while VER values were still increasing. Ovulation was
      earlier in lower parity sows (P < 0.001). Compared to 0 h (ovulation time), VER
      was significantly lower from 50 to 5 h before ovulation in autumn and from 40 to
      21 h in winter, but such differences were not seen in spring. Lowest VER value
      was not correlated with time of ovulation. It was concluded that VER increases
      before ovulation and, although this increase is influenced by the season, it
      cannot be used to accurately predict ovulation in weaned sows. 

PMID- 25852233
TI  - Equid herpesvirus 9 (EHV-9) isolates from zebras in Ontario, Canada, 1989 to
      2007.
AB  - The objective of this study was to identify and partially characterize 3 equid
      herpesviruses that were isolated postmortem from zebras in Ontario, Canada in
      1989, 2002, and 2007. These 3 virus isolates were characterized by plaque
      morphology, restriction fragment length polymorphism (RFLP) of their genomic
      deoxyribonucleic acid (DNA), real-time polymerase chain reaction (PCR) assay, and
      sequence analyses of the full length of the glycoprotein G (gG) gene (ORF70) and
      a portion of the DNA polymerase gene (ORF30). The isolates were also compared to
      3 reference strains of equid herpesvirus 1 (EHV-1). Using rabbit kidney cells,
      the plaques for the isolates from the zebras were found to be much larger in size
      than the EHV-1 reference strains. The RFLP patterns of the zebra viruses differed
      among each other and from those of the EHV-1 reference strains. Real-time PCR and
      sequence analysis of a portion of the DNA polymerase gene determined that the
      herpesvirus isolates from the zebras contained a G at nucleotide 2254 and a
      corresponding N at amino acid position 752, which suggested that they could be
      neuropathogenic EHV-1 strains. However, subsequent phylogenetic analysis of the
      gG gene suggested that they were EHV-9 and not EHV-1. 

PMID- 25852234
TI  - Sleep duration and sleep quality following acute mild traumatic brain injury: a
      propensity score analysis.
AB  - INTRODUCTION: Mild traumatic brain injury (mTBI) has been widely studied and the
      effects of injury can be long term or even lifelong. This research aims to
      characterize the sleep problems of patients following acute mTBI. METHODS: A
      total of 171 patients with mTBI within one month and 145 non-mTBI controls were
      recruited in this study. The questionnaire, Pittsburgh Sleep Quality Index
      (PSQI), was used to evaluate seven aspects of sleep problems. A propensity score
      method was used to generate a quasirandomized design to account for the
      background information, including gender, age, Beck's Anxiety Index, Beck's
      Depression Index, and Epworth Sleepiness Scale. The effect was evaluated via
      cumulative logit regression including propensity scores as a covariate. RESULTS:
      Before adjustment, about 60% mTBI patients and over three quarters of control
      subjects had mild sleep disturbance while one third mTBI patients had moderate
      sleep disturbance. After adjusting by the propensity scores, the scores of sleep
      quality and duration were significant between mTBI and control groups.
      CONCLUSION: Our study supports that sleep problem is common in mTBI group. After
      adjusting the confounders by propensity score, sleep duration and subjective
      sleep quality are the most frequently reported problems in mTBI patients within
      one month after the injury.

PMID- 25852235
TI  - Corrigendum to "hypothermia reduces toll-like receptor 3-activated microglial
      interferon-beta and nitric oxide production".

PMID- 25852236
TI  - Editorial comment: preventing sudden death with implantable defibrillators in
      octogenarians: too much too late?

PMID- 25852238
TI  - Editorial Comment: Over, Under, or Just Right? How do we interpret ICD
      utilization in the modern era?

PMID- 25852237
TI  - Implantable cardioverter defibrillators in octogenarians: clinical outcomes from
      a single center.
AB  - AIMS: Limited data exist on outcomes in very elderly ICD recipients. We describe
      outcomes in new ICD and Cardiac Resynchronisation Therapy with Defibrillator (CRT
      D) implants in octogenarians at our institution. METHODS: Patients aged 80 years
      and above who underwent de novo ICD or CRT-D implantation from January 2006 to
      July 2012 were identified. Clinical data were collected from the procedural
      record, medical and ICD notes. Baseline characteristics were compared using
      independent sample t test for continuous variables and Fisher's exact test for
      categorical variables. Kaplan-Meier curves were constructed. RESULTS: Ten per
      cent of all new ICD/CRT-D implants were aged 80 years and over. Median age was
      83.0 years. Median follow-up was 29 months. Death occurred in 17 (34%). Median
      time to death was 23 months. Three deaths (6%) occurred within 12 months of ICD
      implantation. Appropriate therapy (ATP or shock) occurred in 19 (38%).
      Inappropriate therapy occurred in 6 (12%). Rates of appropriate shocks and
      inappropriate therapy (shocks and ATP) and significant valvular incompetence were
      higher amongst deceased patients (P=0.03 OR 5.9 95% CI 1.3-27) and (P=0.02 OR 12
      95% CI 1.3-112). Univariate analysis identified diuretic use (P=0.008 95% C.I.
      0.05 to 0.63) and appropriate shock (P= 0.025 95% C.I. 1.25 to 26.3) as
      predictors of mortality. CONCLUSION: Octogenarians make up a small but increasing
      number of ICD recipients. This study highlights high survival rates at one year
      with acceptable rates of appropriate and inappropriate device therapy. Ongoing
      debate regarding the appropriateness of ICD in very elderly patients is
      warranted.

PMID- 25852240
TI  - Editorial comment: syncope with heart disease - provoke and see or wait and watch
      ?

PMID- 25852239
TI  - Under-Utilization of Implantable Cardioverter Defibrillators in Patients with
      Heart Failure - The Current State of Sudden Cardiac Death Prophylaxis.
AB  - BACKGROUND: Despite ACC/AHA guidelines indicating implantable cardioverter
      defibrillator (ICD) as class I therapy for primary prevention of sudden cardiac
      death in patients with EF<=35%, ICD utilization rates in real world practice have
      been low. OBJECTIVE: To determine the rate of ICD implantation at a tertiary care
      academic center and to assess the reasons for under-utilization of the same.
      METHODS: Review of a prospectively collected database which included all patients
      diagnosed with an EF<=35% was performed to assess the rate of ICD implantation
      and mortality. Reasons for non-implantation of ICD were then assessed from
      detailed chart review. RESULTS: A total of 707 patients (age 69.4 +/- 14.1 years)
      with mean EF of 26+/-7% were analyzed. Only 28% (200/707) of patients had ICDs
      implanted. Mortality was lower in the group with ICD (25% vs 37%, p=0.004). When
      patients who either died or were lost to follow-up prior to 2005 were excluded,
      ICD utilization rate was still low at 37.6%. The most common reason for non
      implantation of ICD was physicians not discussing this option with their
      patients. Patient refusal was the second most common reason. CONCLUSIONS: ICD
      Implantation rates for primary prevention of SCD in patients with EF<=35% is low.
      Physician and patient education should be addressed to improve the utilization
      rates.

PMID- 25852241
TI  - What is The Utility of Electrophysiological Study in Elderly Patients with
      Syncope and Heart Disease?
AB  - BACKGROUND: Syncope in elderly patients with heart disease is a growing problem.
      Its aetiological diagnosis is often difficult. We intended to investigate the
      value of the electrophysiological study (EPS) in old patients with syncope and
      heart disease. METHODS: EPS was performed in 182 consecutive patients with
      syncope and heart disease, among whom 62 patients were >=75 years old and 120
      patients <75. RESULTS: Left ventricular ejection fraction was 43.9+/-11.7% in
      patients >=75 and 41.1+/-12.6% in patients <75. During EPS, induced sustained
      ventricular arrhythmias were as frequent in both groups (27.4% in patients >=75
      versus 27.5% in patients <75, p=0.99) whereas AV conduction abnormalities were
      more frequent in older patients (37.1% in patients >=75 versus 18.3% in patients
      <75, p<0.005). Syncope remained unexplained in 35.5% of patients >=75 and in
      51.7% of patients <75 (p>0.04). ICD was more likely to be implanted in younger
      patients than in patients >=75 years (37.5% vs 21% respectively, p<0.009). During
      a mean follow-up period of 3.3+/-3 years, the 4-year-survival rate was 66.9+/-6.8
      % in patients >=75 and 75.9+/-6.2 % in patients <75 years. The main cause of
      death was heart failure in both groups. The factors related to a worse outcome in
      a multivariate analysis were low LVEF and higher age. CONCLUSION: Complete EPS
      allows the identification of treatable causes in a high proportion of elderly
      patients with syncope and heart disease. Yet, the prognosis of these patients is
      mainly related to LVEF and age.

PMID- 25852242
TI  - Channelopathies - emerging trends in the management of inherited arrhythmias.
AB  - In spite of their relative rarity, inheritable arrhythmias have come to the
      forefront as a group of potentially fatal but preventable cause of sudden cardiac
      death in children and (young) adults. Comprehensive management of inherited
      arrhythmias includes diagnosing and treating the proband and identifying and
      protecting affected family members. This has been made possible by the vast
      advances in the field of molecular biology enabling better understanding of the
      genetic underpinnings of some of these disease groups, namely congenital long QT
      syndrome, catecholaminergic polymorphic ventricular tachycardia and Brugada
      syndrome. The ensuing knowledge of the genotype-phenotype correlations enables us
      to risk-stratify, prognosticate and treat based on the genetic test results. The
      various diagnostic modalities currently available to us, including clinical tools
      and genetic technologies, have to be applied judiciously in order to promptly
      identify those affected and to spare the emotional burden of a potentially lethal
      disease in the unaffected individuals. The therapeutic armamentarium of inherited
      arrhythmias includes pharmacological agents, device therapies and surgical
      interventions. A treatment strategy keeping in mind the risk profile of the
      patients, the local availability of drugs and the expertise of the treating
      personnel is proving effective. While opportunities for research are numerous in
      this expanding field of medicine, there is also tremendous scope for
      incorporating the emerging trends in managing patients and families with
      inherited arrhythmias in the Indian subcontinent. 

PMID- 25852243
TI  - Antegrade and retrograde decremental conduction properties of an accessory
      pathway associated with the coronary sinus musculature.
AB  - A 32-year-old man underwent catheter ablation of an orthodromic atrioventricular
      reentrant tachycardia. The sinus rhythm electrocardiogram exhibited a normal PQ
      interval and no delta waves, but atrial pacing produced a prolonged PQ interval
      and wide QRS morphology with right bundle-branch block due to antegrade accessory
      pathway (AP) conduction. During the tachycardia, atrial double potentials
      consisting of the coronary sinus musculature (CSM) and left atrial (LA)
      potentials were observed. Ventricular extrastimulation exhibited retrograde
      decremental conduction with an identical atrial activation sequence as during the
      tachycardia. A radiofrequency application within the posterolateral CS during
      ventricular pacing eliminated the CSM-LA conduction and concomitantly the
      ventriculoatrial conduction via the AP was abolished. In this case, the CSM was
      associated with the bidirectional decremental conduction properties of the AP,
      and the antegrade slow conduction resulted in the absence of a shortening of the
      PQ interval and delta waves during sinus rhythm despite the continuous presence
      of antegrade AP conduction. 

PMID- 25852244
TI  - Successful Implant of a Subcutaneous ICD System in a Patient with an Ipsilateral
      Epicardial Pacemaker.

PMID- 25852245
TI  - Novel use of the midas rex neurosurgical drill to release silicone glue entrapped
      pacing leads.

PMID- 25852247
TI  - Jumping across the gap - a series of atrial extrastimuli.
AB  - The "gap phenomenon" is an interesting phenomenon in electrophysiology arising
      from the differences in refractory periods at two or more levels of the
      atrioventricular (AV) conduction system. We present a patient with dual AV nodal
      physiology in whom the AH jump mediates the gap phenomenon. We also briefly
      discuss the other mechanisms of gap phenomenon that have been described in this
      setting. 

PMID- 25852246
TI  - Partial unroofed coronary sinus associated with upper septal ventricular
      tachycardia and atrioventricular nodal reentrant tachycardia.
AB  - A 58 year old gentleman with complaints of palpitations and documented
      tachycardia was found to have a dilated right atrium, right ventricle and
      coronary sinus, which were due to partial unroofed coronary sinus without a left
      superior vena cava. He had upper septal ventricular tachycardia and atrio
      ventricular nodal reentrant tachycardia, which was successfully treated by
      radiofrequency ablation. 

PMID- 25852248
TI  - Peeling off the Mask: Pseudo Myocardial Infarction Pattern on Electrocardiogram
      During AICD Implantation.
AB  - Lead induced transient right bundle branch block is not uncommon during pacemaker
      implantation. We describe a patient with old anterior wall myocardial infarction
      with severe left ventricular dysfunction presenting with recurrent ventricular
      tachycardia who developed transient right bundle branch block and
      pseudomyocardial infacrction pattern during AICD implantation. 

PMID- 25852249
TI  - First Case of Automatic His Potential Detection With a Novel Ultra High-density
      Electroanatomical Mapping System for AV Nodal Ablation.
AB  - A 74-year old was considered for atrioventricular (AV) nodal ablation in view of
      atrial fibrillation (AF) with poorly controlled ventricular rate despite being on
      amiodarone. Targeted AV nodal ablation was successfully performed after
      identifying the target site for ablation by reviewing an ultra high-density map
      of the His region produced by automatic electrogram annotation. 

PMID- 25852250
TI  - Ventricular arrhythmias in arrhythmogenic right ventricular dysplasia.

PMID- 25852251
TI  - Using aripiprazole to reduce antipsychotic-induced hyperprolactinemia: meta
      analysis of currently available randomized controlled trials.
AB  - BACKGROUND: Hyperprolactinemia (HPL) is a common side effect of antipsychotic
      medications. Recent reports suggest that aripiprazole can ameliorate
      antipsychotic-induced HPL, but results are inconsistent and the single available
      systematic review only considered five studies. AIM: Conduct an updated meta
      analysis of all randomized controlled trials (RCTs) about the efficacy and safety
      of aripiprazole as an adjunctive treatment for antipsychotic-induced
      hyperprolactinemia. METHODS: English and Chinese databases were searched for RCTs
      about the use of aripiprazole in treating antipsychotic-induced HPL published by
      January 20, 2015. Studies were selected using pre-defined inclusion and exclusion
      criteria. The Cochrane Risk of Bias tool was used to evaluate risk of biases, the
      Cochrane GRADE measure was used to assess the quality of evidence, and Review
      Manager 5.3 software was used for data analysis. RESULTS: A total of 21 studies,
      19 of which were conducted in mainland China, were included in the analysis. Meta
      analysis of data from 8 of the studies with a pooled sample of 604 individuals
      found that compared to the control condition adjunctive aripiprazole
      significantly increased the proportion of participants who experienced HPL
      recovery (risk ratio [RR]=19.2, 95%CI=11.0-33.5). The proportion who experienced
      any adverse effect during follow-up did not differ between the two groups, but
      the aripiprazole group was more likely to report somnolence (RR=2.76, 95%CI=1.34
      5.69) and headaches (RR=2.31, 95%CI=1.08-4.92). High-dose aripiprazole (>5mg/day)
      was more effective than low-dose (<5mg/day) aripiprazole (RR=30.0, 95%CI=10.2
      120.7 v. RR=15.1, 95%CI=8.1-28.1), but this difference was not statistically
      significant. The risk of bias in the studies was rated as 'high' in 6 of the
      studies and 'unclear' in 15 studies, and the quality of evidence was rated as
      'high' for only 7 of the 57 outcome measures assessed. CONCLUSIONS: This study
      systematically reviewed and evaluated all relevant RCTs and found that adjunctive
      aripiprazole is effective and safe to use in the treatment of antipsychotic
      induced HPL. However, the low quality of some of the studies, the incomplete
      methodological information provided for most of the studies, and the relatively
      short follow-up time of the studies raises question about the validity of the
      results. Further work that resolves these methodological and reporting issues is
      needed.

PMID- 25852252
TI  - Cross-sectional evaluation of the adequacy of guardianship by family members of
      community-residing persons with mental disorders in Changning District, Shanghai.
AB  - BACKGROUND: The disease burden associated with chronic psychiatric illnesses is
      high and is projected to grow rapidly. A community-based management system for
      persons with mental illness was established in Shanghai in 2012 based on the
      Shanghai Mental Health Regulations that were developed to conform with China's
      new mental health law. AIM: Evaluate the guardianship services provided by family
      members to persons with mental illnesses living in the Changning District of
      Shanghai. METHODS: The legal guardians of 4034 of the 4283 community-dwelling
      persons with psychiatric disorders living in Changning District who are
      registered in the Shanghai Information Management System of Mental Health were
      interviewed by local community health doctors and local neighborhood committee
      officials. The adequacy of guardianship was assessed based on standardized
      criteria (including the guardian's regular attendance at mental health training
      sessions, and their level of assistance in the treatment, daily life, and
      rehabilitation of the patient) and the main reasons for inadequate guardianship
      were recorded. RESULTS: The majority of guardians (3331, 83.6%) adequately
      fulfilled their guardianship duties. Advanced age and ill-health of the guardian
      was the main contributing factor in 87% of the 703 cases in which the
      guardianship was classified as inadequate. Other factors associated with
      inadequate guardianship included the patient's unstable clinical condition or
      failure to adhere to medication, and when the guardian did not live in the same
      household as the patient. The patient's diagnosis, the guardian's level of
      education, and the relationship between the guardian and patient were also
      associated with the adequacy of guardianship. CONCLUSIONS: The guardianship-based
      community services for mentally ill individuals in urban China works reasonably
      well. But the rapid aging of China's population may gradually decrease the
      ability of China's families to continue to assume this heavy burden. Alternative
      models of providing high-quality, community-based services for persons with
      mental disorders need to be developed as part of the roll-out of China's new
      mental health law.

PMID- 25852253
TI  - Social media and suicide prevention: findings from a stakeholder survey.
AB  - BACKGROUND: Suicide is a leading cause of death, particularly among young adults.
      The rapid growth of social media and its heavy use by young adults presents new
      challenges and opportunities for suicide prevention. Social media sites are
      commonly used for communicating about suicide-related behavior with others, which
      raises the possibility of using social media to help prevent suicide. However,
      the use of social media varies widely between different suicide prevention
      advocates. The role this type of intervention should play in a community's
      overall suicide prevention strategy remains a matter of debate. AIM: Explore the
      ways in which stakeholders use social media for suicide prevention and assess
      their views about the potential utility of social media as a suicide prevention
      tool. METHODS: A 12-week stakeholder consultation that involved the online
      administration and completion of surveys by 10 individuals who conduct research
      about suicide and social media, 13 organizations that use social media for
      suicide prevention purposes, and 64 users of social media. RESULTS: Social media
      was seen as a useful means of delivering a range of suicide prevention
      activities. Respondents reported that the key benefits of social media were the
      opportunity to obtain emotional support from others, to express one's feelings,
      to talk to others with similar problems, and to provide help to others. The
      social media site believed to hold most potential for delivering suicide
      prevention activities was Facebook. There were concerns about potential risks of
      social media, but respondents felt the potential benefits outweighed the risks.
      CONCLUSIONS: Social media was recognized by different types of stakeholders as
      holding potential for delivering suicide prevention activities. More research is
      required to establish the efficacy and safety of potential social media-based
      interventions and ethical standards and protocols to ensure that such
      interventions are delivered safely need to be developed and implemented.

PMID- 25852254
TI  - Comparison of the personality and other psychological factors of students with
      internet addiction who do and do not have associated social dysfunction.
AB  - BACKGROUND: There is ongoing controversy about whether or not internet addiction
      should be considered a non-substance behavioral addiction (like gambling
      disorder) and, if so, what diagnostic criteria should be used to define the
      condition. Current criteria for internet addiction give equal diagnostic weight
      to the physiological symptoms and the social consequences of internet addiction.
      AIM: Assess the psychological correlates of social dysfunction among individuals
      with internet addiction. METHODS: A total of 133 students who sought treatment at
      the Guangji Psychiatric Hospital from July 2011 to December 2013 for
      psychological problems related to excessive internet use and who currently met
      Young criteria for internet addiction were identified; 31 of the 38 students who
      meet rigorous criteria for concurrent internet-related social dysfunction and a
      random sample of 44 of the 95 students without concurrent social dysfunction
      completed a battery of psychosocial measures: seven supplementary scales of the
      Minnesota Multiphasic Personality Inventory (MMPI), the Egna Minnen av Barndoms
      Uppfostran perceived parenting scale, the Perceived Social Support Scale, the
      Trait Coping Style Questionnaire, and the Symptom Checklist 90. RESULTS: Compared
      to persons with internet addiction without accompanying social dysfunction, those
      with social dysfunction had higher levels of interpersonal sensitivity,
      hostility, and paranoia; lower levels of social responsibility, anxiety, self
      control, and family social support; and they were more likely to employ negative
      coping strategies. There were however, no differences in perceived parenting
      styles between the two groups. CONCLUSIONS: A relatively small proportion of
      individuals who meet the physiological markers of internet addiction
      simultaneously report significant internet-related social dysfunction. There are
      several psychosocial measures that distinguish persons with internet addiction
      who do or do not have concurrent social dysfunction. Further research is needed
      to determine whether or not these are two distinct subtypes of internet addiction
      and whether or not persons with internet addiction without concurrent social
      dysfunction should be classified as suffering from a 'mental disorder'.

PMID- 25852255
TI  - Psychosis risk syndrome is not prodromal psychosis.
AB  - One of the most exciting trends in schizophrenia research is the shift in focus
      from treatment studies to studies about the early identification and prevention
      of schizophrenia. These studies have primarily focused on adolescents or young
      adults with prodromal symptoms or on clinically high-risk individuals who show
      similar impairments in cognitive and social functioning to those seen in
      individuals with schizophrenia and, thus, are considered at high risk of
      developing schizophrenia or other psychotic disorders. Some researchers have
      labeled this condition as psychosis risk syndrome (PRS). There are moves in some
      circles to re-define the condition as a disorder in its own right: the American
      Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders
      5(th) edition (DSM-5), lists 'attenuated psychosis syndrome' (APS) in the
      appendix as a condition for further study. Individuals with PRS are certainly at
      higher risk of developing a psychotic disorder than those without PRS, but the
      majority of those with PRS do not subsequently develop a psychotic disorder, so
      we argue against the inclusion of PRS or APS as a subtype of schizophrenia
      spectrum disorder. 

PMID- 25852256
TI  - Challenges in the early detection and intervention of the psychosis-risk
      syndrome.
AB  - The concept of a clinical high-risk state for psychosis has been used to describe
      individuals who have prodromal symptoms of psychosis and, thus, are at high-risk
      of developing psychosis. This high-risk concept promotes a more detailed
      developmental understanding of the evolution of psychosis and provides a
      theoretical basis for providing necessary mental health services to people at
      clinically high-risk of developing psychosis. Early detection and intervention
      can potentially change the course of psychotic conditions and, thus, prevent or
      minimize the associated disability. This is a relatively new area of interest, so
      more studies are needed to fully understand this high-risk condition. 

PMID- 25852257
TI  - Attenuated psychosis syndrome: benefits of explicit recognition.
AB  - Given the unique characteristics of people who meet criteria for attenuated
      psychosis syndrome (APS) and the growing literature on the clinical benefits of
      providing services to individuals who meet these criteria, the APS diagnosis
      serves an important, and previously missing, role in psychiatry. The promotion of
      the APS diagnosis should help reduce the over-diagnosis and over-treatment of
      individuals with prodromal psychotic conditions and it should also encourage
      expanded training about attenuated psychosis among clinicians who primarily
      provide services to youth (a primary group who are diagnosed with APS). Only some
      of the individuals with APS subsequently develop psychosis, but all have existing
      clinical needs - regardless of subsequent conversion. The formal recognition of
      APS in DSM-5 will facilitate the research needed to identify and meet those
      needs. 

PMID- 25852258
TI  - Case report of rabies-induced persistent mental symptoms.
AB  - Rabies is a viral infection with a high case fatality rate. Typical symptoms of
      rabies include hydrophobia, pharynx muscle spasms, and progressive paralysis.
      Rabies-induced persistent mental disturbances are rare. Here we report a 22-year
      old male who was infected with rabies after being attacked by a dog. He did not
      receive rabies vaccine immediately after the incident and was only provided with
      non-standard treatment at a local clinic. A week later he became disorientated,
      paranoid, and aggressive. One month after the attack, rabies antibody was found
      in his cerebrospinal fluid and a Magnetic Resonance Imaging (MRI) examination of
      his head revealed abnormal signals in the putamina, caudate nucleus, and insula.
      His mental symptoms persisted for six years and his daily functioning was
      severely impaired, but his vital signs were stable without signs of brain stem
      damage. Six years after the incident, a repeat MRI showed brain atrophy. 

PMID- 25852259
TI  - Brief Chinese version of the Family Experience Interview Schedule to assess
      caregiver burden of family members of individuals with mental disorders.
AB  - BACKGROUND: Caregiver burden is an important issue that needs to be addressed
      when developing management programs for persons with chronic mental illnesses,
      but there is, as yet, no reliable way for assessing this in China. AIM: Assess
      the validity and reliability of a brief adapted Chinese version of the Family
      Experience Interview Schedule (FEIS) among caregivers of inpatients with mental
      disorders in China. METHODS: We first translated and back-translated the original
      114-item FEIS and administered it to 606 primary caregivers of psychiatric
      inpatients. After excluding 9 items about sociodemographic variables and 9 items
      that over 15% of respondents were unable to answer, we conducted an exploratory
      factor analysis using a random half of the sample on the remaining 96 items and,
      based on the results of the factor analysis, selected the items to be included in
      the final shortened scale. Correlation analysis, confirmatory factor analysis,
      and internal consistency measures were used to assess the reliability and
      validity of the final scale using data from the second half of the sample.
      RESULTS: The final scale included 28 items that loaded on five dimensions: (a)
      patients' violent behavior; (b) patients' suicidal tendency; (c) caregivers'
      depression and anxiety; (d) disruption of caregivers' daily routines; and (e)
      caregivers' satisfaction with health services. These five dimensions explained
      50.5% of the total variance. Confirmatory factor analysis found reasonable fit of
      this 5-factor model (chi (2) /df=2.94, p<0.001, goodness-of-fit index [GFI]=0.85,
      comparative fit index [CFI]=0.85, root-mean-square error of approximation
      [RMSEA]=0.08). The correlation coefficients between each item and the
      corresponding factor were all above 0.5. The Cronbach alpha coefficient of the
      entire scale was 0.76 and that for the five dimensions varied between 0.71 and
      0.84. CONCLUSION: The five dimensions of family burden assessed by the 28-item
      brief Chinese version of FEIS have good internal consistency and, thus, appear to
      assess valid dimensions of family burden in Chinese caregivers of persons with
      serious mental illnesses. Further work is needed to assess the test-retest
      reliability of this scale and its sensitivity to change over time.

PMID- 25852260
TI  - Kappa coefficient: a popular measure of rater agreement.
AB  - In mental health and psychosocial studies it is often necessary to report on the
      between-rater agreement of measures used in the study. This paper discusses the
      concept of agreement, highlighting its fundamental difference from correlation.
      Several examples demonstrate how to compute the kappa coefficient - a popular
      statistic for measuring agreement - both by hand and by using statistical
      software packages such as SAS and SPSS. Real study data are used to illustrate
      how to use and interpret this coefficient in clinical research and practice. The
      article concludes with a discussion of the limitations of the coefficient. 

PMID- 25852261
TI  - Field cancerisation in colorectal cancer: a new frontier or pastures past?
AB  - Despite considerable advances in our understanding of cancer biology, early
      diagnosis of colorectal cancer remains elusive. Based on the adenoma-carcinoma
      sequence, cancer develops through the progressive accumulation of mutations in
      key genes that regulate cell growth. However, recent mathematical modelling
      suggests that some of these genetic events occur prior to the development of any
      discernible histological abnormality. Cells acquire pro-tumourigenic mutations
      that are not able to produce morphological change but predispose to cancer
      formation. These cells can grow to form large patches of mucosa from which a
      cancer arises. This process has been termed "field cancerisation". It has
      received little attention in the scientific literature until recently. Several
      studies have now demonstrated cellular, genetic and epigenetic alterations in the
      macroscopically normal mucosa of colorectal cancer patients. In some reports,
      these changes were effectively utilised to identify patients with a neoplastic
      lesion suggesting potential application in the clinical setting. In this article,
      we present the scientific evidence to support field cancerisation in colorectal
      cancer and discuss important limitations that require further investigation.
      Characterisation of the field defect is necessary to enable early diagnosis of
      colorectal cancer and identify molecular targets for chemoprevention. Field
      cancerisation offers a promising prospect for experimental cancer research and
      has potential to improve patient outcomes in the clinical setting. 

PMID- 25852262
TI  - Helicobacter pylori eradication in gastric diffuse large B cell lymphoma.
AB  - Diffuse large B cell lymphoma (DLBCL) of the stomach is a heterogenous disease.
      There are tumors without histological evidence of mucosa-associated lymphoid
      tissue (MALT) lymphoma, which are classified as pure or de novo DLBCL and those
      with evidence of MALT, which are classified as DLBCL (MALT). The association
      between Helicobacter pylori (H. pylori) and gastric MALT lymphoma and remission
      with H. pylori eradication was shown in the 1990s. In recent years, scientists
      from Taiwan and others have shown that high-grade gastric lymphomas may be
      dependent on H. pylori and eradication of this microorganism is effective in
      these cases. This entity is biologically distinct from H. pylori (-) cases and
      has a better clinical outcome. There are sufficient data about the complete
      remission in some of these cases with brief treatment with antibiotics. With this
      strategy, it is possible to save some of these cases from the harmful effects of
      standard chemotherapy. It is time to treat these cases with H. pylori
      eradication. However, strict histopathological follow-up is crucial and
      histopathological response must be evaluated according to the scoring system
      proposed by Groupe d'Etude des Lymphomes de l'Adulte. If there is no sufficient
      response, chemotherapy must be given immediately. These results suggest that H.
      pylori dependency and high-grade transformation in gastric MALT lymphomas are
      distinct events. 

PMID- 25852263
TI  - Current pharmacological therapies for nonalcoholic fatty liver
      disease/nonalcoholic steatohepatitis.
AB  - Nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) is
      considered to be a hepatic manifestation of metabolic syndrome, and its incidence
      is rapidly increasing worldwide. It is currently the most common chronic liver
      disease. NASH can progress to liver cirrhosis and hepatocellular carcinoma, and
      may result in liver-related death. Currently, the principal treatment for
      NAFLD/NASH is lifestyle modification by diet and exercise. However,
      pharmacological therapy is indispensable because obese patients with NAFLD often
      have difficulty maintaining improved lifestyles. The pathogenesis of NAFLD/NASH
      has not been completely elucidated. However, insulin resistance, inflammatory
      cytokines, and oxidative stress are thought to be important in the development
      and/or progression of the disease. Currently, insulin sensitizers
      (thiazolidinediones) and antioxidants (vitamin E) seem to be the most promising
      therapeutic agents for NAFLD/NASH, and lipid-lowering drugs, pentoxifylline,
      angiotensin receptor blockers, and n-3 polyunsaturated fatty acids also have
      promise. However, there is a lack of consensus regarding the most effective and
      appropriate pharmacotherapy for NAFLD/NASH. Animal experiments suggest that
      herbal medicines and natural products may be promising therapeutic agents for
      NAFLD/NASH, but their efficacy and safety are yet to be investigated in human
      studies. In this paper, we review the existing and potential pharmacological
      therapies for NAFLD/NASH. 

PMID- 25852265
TI  - Gastrointestinal Behcet's disease: a review.
AB  - Behcet's disease (BD) is an idiopathic, chronic, relapsing, multi-systemic
      vasculitis characterized by recurrent oral and genital aphthous ulcers, ocular
      disease and skin lesions. Prevalence of BD is highest in countries along the
      ancient silk road from the Mediterranean basin to East Asia. By comparison, the
      prevalence in North American and Northern European countries is low.
      Gastrointestinal manifestations of Behcet's disease are of particular importance
      as they are associated with significant morbidity and mortality. Although
      ileocecal involvement is most commonly described, BD may involve any segment of
      the intestinal tract as well as the various organs within the gastrointestinal
      system. Diagnosis is based on clinical criteria - there are no pathognomonic
      laboratory tests. Methods for monitoring disease activity on therapy are
      available but imperfect. Evidence-based treatment strategies are lacking.
      Different classes of medications have been successfully used for the treatment of
      intestinal BD which include 5-aminosalicylic acid, corticosteroids,
      immunomodulators, and anti-tumor necrosis factor alpha monoclonal antibody
      therapy. Like inflammatory bowel disease, surgery is reserved for those who are
      resistant to medical therapy. A subset of patients have a poor disease course.
      Accurate methods to detect these patients and the optimal strategy for their
      treatment are not known at this time. 

PMID- 25852264
TI  - Hepatitis C virus and antiviral innate immunity: who wins at tug-of-war?
AB  - Hepatitis C virus (HCV) is a major human pathogen of chronic hepatitis and
      related liver diseases. Innate immunity is the first line of defense against
      invading foreign pathogens, and its activation is dependent on the recognition of
      these pathogens by several key sensors. The interferon (IFN) system plays an
      essential role in the restriction of HCV infection via the induction of hundreds
      of IFN-stimulated genes (ISGs) that inhibit viral replication and spread.
      However, numerous factors that trigger immune dysregulation, including viral
      factors and host genetic factors, can help HCV to escape host immune response,
      facilitating viral persistence. In this review, we aim to summarize recent
      advances in understanding the innate immune response to HCV infection and the
      mechanisms of ISGs to suppress viral survival, as well as the immune evasion
      strategies for chronic HCV infection. 

PMID- 25852266
TI  - New gene therapy strategies for hepatic fibrosis.
AB  - The liver is the largest internal organ of the body, which may suffer acute or
      chronic injury induced by many factors, leading to cirrhosis and hepatocarcinoma.
      Cirrhosis is the irreversible end result of fibrous scarring and hepatocellular
      regeneration, characterized by diffuse disorganization of the normal hepatic
      structure, regenerative nodules and fibrotic tissue. Cirrhosis is associated with
      a high co-morbidity and mortality without effective treatment, and much research
      has been aimed at developing new therapeutic strategies to guarantee recovery.
      Liver-based gene therapy has been used to downregulate specific genes, to block
      the expression of deleterious genes, to delivery therapeutic genes, to prevent
      allograft rejection and to augment liver regeneration. Viral and non-viral
      vectors have been used, with viral vectors proving to be more efficient. This
      review provides an overview of the main strategies used in liver-gene therapy
      represented by non-viral vectors, viral vectors, novel administration methods
      like hydrodynamic injection, hybrids of two viral vectors and blocking molecules,
      with the hope of translating findings from the laboratory to the patient's bed
      side.

PMID- 25852268
TI  - Hepatic artery infusion chemotherapy for advanced hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide.
      Surgery, percutaneous ablation and liver transplantation are the only curative
      treatment modalities for HCC. However, the majority of patients have unresectable
      disease at diagnosis. Therefore, effective treatment options for patients with
      advanced HCC are required. In advanced HCC, according to current international
      guidelines, sorafenib, a molecular targeted agent, is the standard treatment.
      However, alternative treatment modalities are required because of the low
      response rates and unsuitability of molecular agents in real practice. In various
      treatment modalities, mostly in Asia, hepatic arterial infusion chemotherapy
      (HAIC) has been applied to advanced HCC with a view to increasing the therapeutic
      efficacy. HAIC provides direct drug delivery into the tumor feeding vessels and
      also minimizes systemic toxicities through a greater first-pass effect in the
      liver. However, the sample sizes of studies on HAIC have been small and large
      randomized trials are still lacking. In this article, we describe the treatment
      efficacy of HAIC for advanced stage HCC and discuss future therapeutic
      possibilities. 

PMID- 25852267
TI  - Current management of hepatocellular carcinoma: an Eastern perspective.
AB  - Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death,
      especially in Eastern areas. With advancements in diagnosis and treatment
      modalities for HCC, the survival and prognosis of HCC patients are improving.
      However, treatment patterns are not uniform between areas despite efforts to
      promote a common protocol. Although many hepatologists in Asian countries may
      adopt the principles of the Barcelona Clinic Liver Cancer staging system, they
      are also independently making an effort to expand the indications of each
      treatment and to combine therapies for better outcomes. Several expanded criteria
      for liver transplantation in HCC have been developed in Asian countries. Living
      donor liver transplantation is much more commonly performed in these countries
      than deceased donor liver transplantation, and it may be preceded by other
      treatments such as the down-staging of tumors. Local ablation therapies are often
      combined with transarterial chemoembolization (TACE) and the outcome is
      comparable to that of surgical resection. The indications of TACE are expanding,
      and there are new types of transarterial therapies. Although data on drug-eluting
      beads, TACE, and radioembolization in Asian countries are still relatively sparse
      compared with Western countries, these methods are gradually gaining popularity
      because of better tolerability and the possibility of improved response rates.
      Hepatic arterial infusion chemotherapy and radiotherapy are not included in
      Western guidelines, but are currently being used actively in several Asian
      countries. For more advanced HCCs, appropriate combinations of TACE,
      radiotherapy, and sorafenib can be considered, and emerging data indicate
      improved outcomes of combination therapies compared with single therapies. To
      include these paradigm shifts into newer treatment guidelines, more studies may
      be needed, but they are certainly in progress. 

PMID- 25852269
TI  - Adjuvant therapy for gastric cancer: what have we learned since INT0116?
AB  - Gastric cancer is one of the main cancer-related causes of death worldwide. The
      curative treatment of gastric cancer consists of tumor resection and
      lymphadenectomy. However, surgical treatment alone is associated with high
      recurrence rates. Adjuvant treatment strategies have been studied over the last
      decades, but there have been controversial results from the initial studies. The
      pivotal INT0116 study demonstrated that the use of adjuvant chemoradiotherapy
      with 5-fluorouracil increases relapse-free and overall survival, and it has been
      adopted across the Western world. The high toxicity of radiochemotherapy and
      suboptimal surgical treatment employed, with fewer than 10% of the patients
      submitted to D2 lymphadenectomy, were the main study limitations. Since its
      publication, other adjuvant treatment modalities have been studied, and
      radiochemotherapy is being refined to improve its efficacy and safety. A
      multimodal approach has been demonstrated to significantly increase relapse-free
      and overall survival, and it can be offered in the form of perioperative
      chemotherapy, adjuvant chemoradiotherapy or adjuvant chemotherapy, regardless of
      the extent of lymphadenectomy. The objective of the present review is to report
      the major advances obtained in the last decades in the adjuvant treatment of
      gastric cancer as well as the perspectives of treatment based on recent knowledge
      of the molecular biology of the disease. 

PMID- 25852270
TI  - Antiviral therapies for hepatitis B virus-related hepatocellular carcinoma.
AB  - Chronic hepatitis B virus (HBV) infection is a critical risk factor for the
      carcinogenesis and progression of hepatocellular carcinoma (HCC). It promotes HCC
      development by inducing liver fibrogenesis, genetic and epigenetic alterations,
      and the expression of active viral-coded proteins. Effective antiviral treatments
      inhibit the replication of HBV, reduce serum viral load and accelerate hepatitis
      B e antigen serum conversion. Timely initiation of antiviral treatment is not
      only essential for preventing the incidence of HCC in chronic hepatitis B
      patients, but also important for reducing HBV reactivation, improving liver
      function, reducing or delaying HCC recurrence, and prolonging overall survival of
      HBV-related HCC patients after curative and palliative therapies. The selection
      of antiviral drugs, monitoring of indicators such as HBV DNA and hepatitis B
      surface antigen, and timely rescue treatment when necessary, are essential in
      antiviral therapies for HBV-related HCC. 

PMID- 25852272
TI  - Fucosylation is a common glycosylation type in pancreatic cancer stem cell-like
      phenotypes.
AB  - AIM: To evaluate/isolate cancer stem cells (CSCs) from tissue or cell lines
      according to various definitions and cell surface markers. METHODS: Lectin
      microarray analysis was conducted on CSC-like fractions of the human pancreatic
      cancer cell line Panc1 by establishing anti-cancer drug-resistant cells. Changes
      in glycan structure of CSC-like cells were also investigated in sphere-forming
      cells as well as in CSC fractions obtained from overexpression of CD24 and CD44.
      RESULTS: Several types of fucosylation were increased under these conditions, and
      the expression of fucosylation regulatory genes such as fucosyltransferases, GDP
      fucose synthetic enzymes, and GDP-fucose transporters were dramatically enhanced
      in CSC-like cells. These changes were significant in gemcitabine-resistant cells
      and sphere cells of a human pancreatic cancer cell line, Panc1. However,
      downregulation of cellular fucosylation by knockdown of the GDP-fucose
      transporter did not alter gemcitabine resistance, indicating that increased
      cellular fucosylation is a result of CSC-like transformation. CONCLUSION:
      Fucosylation might be a biomarker of CSC-like cells in pancreatic cancer.

PMID- 25852271
TI  - Insulin-like growth factor-1 mRNA isoforms and insulin-like growth factor-1
      receptor mRNA expression in chronic hepatitis C.
AB  - AIM: To evaluate the expression of different insulin-like growth factor (IGF)-1
      mRNA isoforms and IGF-1 receptor (IGF-1R) mRNA in hepatitis C virus (HCV)
      infected livers. METHODS: Thirty-four liver biopsy specimens from chronic
      hepatitis C (CH-C) patients were obtained before anti-viral therapy. Inflammatory
      activity (grading) and advancement of fibrosis (staging) were evaluated using a
      modified point scale of METAVIR. The samples were analyzed using quantitative
      real-time PCR technique. From fragments of liver biopsies and control liver that
      were divided and ground in liquid nitrogen, RNA was isolated using RNeasy Fibrous
      Tissue Mini Kit according to the manufacturer's instruction. Expression levels of
      IGF-1 mRNA isoforms (IGF-1A, IGF-1B, IGF-1C, P1, and P2) and IGF-1R mRNA were
      determined through normalization of copy numbers in samples as related to
      reference genes: glyceraldehyde-3-phosphate dehydrogenase and hydroxymethylbilane
      synthase. Results on liver expression of the IGF-1 mRNA isoforms and IGF-1R
      transcript were compared to histological alterations in liver biopsies and with
      selected clinical data in the patients. Statistical analysis was performed using
      Statistica PL v. 9 software. RESULTS: The study showed differences in
      quantitative expression of IGF-1 mRNA variants in HCV-infected livers, as
      compared to the control. Higher relative expression of total IGF-1 mRNA and of
      IGF-1 mRNAs isoforms (P1, A, and C) in HCV-infected livers as compared to the
      control were detected. Within both groups, expression of the IGF-1A mRNA isoform
      significantly prevailed over expressions of B and C isoforms. Expression of P1
      mRNA was higher than that of P2 only in CH-C. Very high positive correlations
      were detected between reciprocal expressions of IGF-1 mRNA isoforms P1 and P2 (r
      = 0.876). Expression of P1 and P2 mRNA correlated with IGF-1A mRNA (r = 0.891; r
      = 0.821, respectively), with IGF-1B mRNA (r = 0.854; r = 0.813, respectively),
      and with IGF-1C mRNA (r = 0.839; r = 0.741, respectively). Expression of IGF-1A
      mRNA significantly correlated with isoform B and C mRNA (r = 0.956; r = 0.869,
      respectively), and B with C isoforms (r = 0.868) (P < 0.05 in all cases). Lower
      expression of IGF-1A and B transcripts was noted in the more advanced liver
      grading (G2) as compared to G1. Multiple negative correlations were detected
      between expression of various IGF-1 transcripts and clinical data (e.g., alpha
      fetoprotein, HCV RNA, steatosis, grading, and staging). Expression of IGF-1R mRNA
      manifested positive correlation with grading and HCV-RNA. CONCLUSION: Differences
      in quantitative expression of IGF-1 mRNA isoforms in HCV-infected livers, as
      compared to the control, suggest that HCV may induce alteration of IGF-1 splicing
      profile.

PMID- 25852273
TI  - Esophageal variceal pressure influence on the effect of ligation.
AB  - AIM: To explore the effect of in vitro porcine esophageal variceal pressure on
      complete ligation degree for polycyclic ligators. METHODS: An in vitro model of
      experimental porcine venous vessels was used to test various venous pressures.
      Three treatment groups were designated according to the preset pressure range: P1
      = 25-30 cmH2O; P2 = 35-40 cmH2O; P3 = 45-50 cmH2O. The effect of pressure on
      ligation was assessed and compared among the groups. RESULTS: Complete ligation
      was achieved at a rate of 56.25% (18/32) in group P1, 37.5% (12/32) in group P2,
      and 33.33% (11/33) in group P3 (chi (2) = 3.6126; P = 0.0573). CONCLUSION: Higher
      variceal pressures impair the ligation completion rate. Therefore, measuring
      variceal pressure may help predict the effect of endoscopic ligation and guide
      treatment choice.

PMID- 25852274
TI  - Caffeic acid phenethyl ester inhibits liver fibrosis in rats.
AB  - AIM: To investigate the hepatoprotective effects and antioxidant activity of
      caffeic acid phenethyl ester (CAPE) in rats with liver fibrosis. METHODS: A total
      of 75 male Sprague-Dawley rats were randomly assigned to seven experimental
      groups: a normal group (n = 10), a vehicle group (n = 10), a model group (n =
      15), a vitamin E group (n = 10), and three CAPE groups (CAPE 3, 6 and 12 mg/kg, n
      = 10, respectively). Liver fibrosis was induced in rats by injecting CCl4
      subcutaneously, feeding with high fat forage, and administering 30% alcohol
      orally for 10 wk. Concurrently, CAPE (3, 6 and 12 mg/kg) was intraperitoneally
      administered daily for 10 wk. After that, serum total bilirubin (TBil),
      aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured
      to assess hepatotoxicity. To investigate antioxidant activity of CAPE,
      malondialdehyde (MDA), glutathione (GSH) levels, catalase (CAT) and superoxide
      dismutase (SOD) activities in liver tissue were determined. Moreover, the effect
      of CAPE on alpha-smooth muscle actin (alpha-SMA), a characteristic hallmark of
      activated hepatic stellate cells (HSCs), and NF-E2-related factor 2 (Nrf2), a key
      transcription factor for antioxidant systems, was investigated by
      immunohistochemistry. RESULTS: Compared to the model group, intraperitoneal
      administration of CAPE decreased TBil, ALT, and AST levels in liver fibrosis rats
      (P < 0.05), while serum TBil was decreased by CAPE in a dose-dependent manner. In
      addition, the liver hydroxyproline contents in both the 6 and 12 mg/kg CAPE
      groups were markedly lower than that in the model group (P < 0.05 and P < 0.001,
      respectively). CAPE markedly decreased MDA levels and, in turn, increased GSH
      levels, as well as CAT and SOD activities in liver fibrosis rats compared to the
      model group (P < 0.05). Moreover, CAPE effectively inhibited alpha-SMA expression
      while increasing Nrf2 expression compared to the model group (P < 0.01).
      CONCLUSION: The protective effects of CAPE against liver fibrosis may be due to
      its ability to suppress the activation of HSCs by inhibiting oxidative stress.

PMID- 25852275
TI  - Interferon-lambda3 polymorphisms in pegylated-interferon-alpha plus ribavirin
      therapy for genotype-2 chronic hepatitis C.
AB  - AIM: To evaluate interferon-lambda3 (IFNL3) polymorphisms in response-guided
      pegylated interferon-alpha plus ribavirin (Peg-IFNalpha/RBV) therapy for genotype
      2 (G2) chronic hepatitis C. METHODS: Between January 2006 and June 2012, a total
      of 180 patients with chronic infections of G2 hepatitis C virus (HCV) were
      treated with response-guided Peg-IFNalpha/RBV therapy. The treatment duration was
      24 wk for patients who achieved rapid virologic response (RVR), and 36 or 48 wk
      for patients who did not. Then, the impact of the IFNL3 single nucleotide
      polymorphism genotype (TT/non-TT at rs8099917) on treatment outcomes was
      evaluated in the 180 patients, and between patients infected with either HCV sub
      genotype 2a or 2b. RESULTS: Of the 180 patients evaluated, 111 achieved RVR,
      while the remaining 69 patients did not. In RVR patients, the sustained virologic
      response (SVR) rate was 96.4%, and the IFNL3 genotype did not influence the SVR
      rate (96.6% vs 95.8% in IFNL3 genotype TT vs non-TT). However, in non-RVR
      patients, the SVR rate decreased to 72.5% (P < 0.0001), and this rate was
      significantly different between the IFNL3 genotype TT and non-TT groups (80.0% vs
      42.9%, P = 0.0146). Multivariate regression analysis in non-RVR patients
      identified the IFNL3 genotype TT as the only baseline-significant factor
      associated with SVR (OR = 5.39, 95%CI: 1.29-22.62; P = 0.0189). In analysis
      according to HCV sub-genotype, no significant difference in the SVR rate was
      found between HCV sub-genotypes 2a and 2b. CONCLUSION: In response-guided Peg
      IFNalpha/RBV combination therapy for chronically HCV G2-infected patients, the
      impact of the IFNL3 genotype on SVR was limited to non-RVR patients.

PMID- 25852276
TI  - Hepatitis C virus recurrence after liver transplantation: a 10-year evaluation.
AB  - AIM: To evaluate the predictors of 10-year survival of patients with hepatitis C
      recurrence. METHODS: Data from 358 patients transplanted between 1989 and 2010 in
      two Italian transplant centers and with evidence of hepatitis C recurrence were
      analyzed. A chi(2), Fisher's exact test and Kruskal Wallis' test were used for
      categorical and continuous variables, respectively. Survival analysis was
      performed at 10 years after transplant using the Kaplan-Meier method, and a log
      rank test was used to compare groups. A P level less than 0.05 was considered
      significant for all tests. Multivariate analysis of the predictive role of
      different variables on 10-year survival was performed by a stepwise Cox logistic
      regression. RESULTS: The ten-year survival of the entire population was 61.2%.
      Five groups of patients were identified according to the virological response or
      lack of a response to antiviral treatment and, among those who were not treated,
      according to the clinical status (mild hepatitis C recurrence, "too sick to be
      treated" and patients with comorbidities contraindicating the treatment). While
      the 10-year survival of treated and untreated patients was not different (59.1%
      vs 64.7%, P = 0.192), patients with a sustained virological response had a higher
      10-year survival rate than both the "non-responders" (84.7% vs 39.8%, P < 0.0001)
      and too sick to be treated (84.7% vs 0%, P < 0.0001). Sustained virological
      responders had a survival rate comparable to patients untreated with mild
      recurrence (84.7% vs 89.3%). A sustained virological response and young donor age
      were independent predictors of 10-year survival. CONCLUSION: Sustained
      virological response significantly increased long-term survival. Awaiting the
      interferon-free regimen global availability, antiviral treatment might be
      questionable in selected subjects with mild hepatitis C recurrence.

PMID- 25852277
TI  - Clinical and computed tomography findings of appendiceal diverticulitis vs acute
      appendicitis.
AB  - AIM: To study the clinical features and computed tomography (CT) findings of
      appendiceal diverticulitis vs acute appendicitis. METHODS: We retrospectively
      reviewed the records of 451 patients who had undergone appendectomy in our
      institution from January 2007 to September 2012. Patient demographics, clinical
      features, pathological findings, and surgical outcomes were analyzed. We also
      compared preoperative CT images of 25 patients with appendiceal diverticulitis
      with those of 25 patients with acute appendicitis. RESULTS: Among 451 patients,
      44 (9.7%) were diagnosed to have appendiceal diverticulitis and 398 (86.9%) to
      have acute appendicitis. Patients with appendiceal diverticulitis were older (59
      vs 37 years, P < 0.001) and had a longer duration of the illness (4.0 d vs 1.0 d,
      P < 0.001). Perforation rates in patients with appendiceal diverticulitis were
      higher (68% vs 27%, P < 0.001). The appendix could be visualized in only 13
      patients (52%) among the appendiceal diverticulitis cases, but in all acute
      appendicitis cases. CT findings suggestive of appendiceal diverticulitis included
      the absence of fluid collection in the appendix (84% vs 12%, P < 0.001), absence
      of appendicolith (92% vs 52%, P = 0.005), and formation of abscess (68% vs 16%, P
      < 0.001). Appendiceal diverticula were identified in 6 patients (24%).
      CONCLUSION: Among patients who had undergone appendectomy, 9.7% had appendiceal
      diverticulitis. Patients with appendiceal diverticulitis had different clinical
      features and CT findings from patients with acute appendicitis.

PMID- 25852278
TI  - Diagnostic value of PIVKA-II and alpha-fetoprotein in hepatitis B virus
      associated hepatocellular carcinoma.
AB  - AIM: To determine the cutoff values and to compare the diagnostic role of alpha
      fetoprotein (AFP) and prothrombin induced by vitamin K absence-II (PIVKA-II) in
      chronic hepatitis B (CHB). METHODS: A total of 1255 patients with CHB, including
      157 patients with hepatocellular carcinoma (HCC), 879 with non-cirrhotic CHB and
      219 with cirrhosis without HCC, were retrospectively enrolled. The areas under
      the receiver operating characteristic (AUROC) curves of PIVKA-II, AFP and their
      combination were calculated and compared. RESULTS: The optimal cutoff values for
      PIVKA-II and AFP were 40 mAU/mL and 10 ng/mL, respectively, for the
      differentiation of HCC from nonmalignant CHB. The sensitivity and specificity
      were 73.9% and 89.7%, respectively, for PIVKA-II and 67.5% and 90.3% for AFP,
      respectively. The AUROC curves of both PIVKA-II and AFP were not significantly
      different (0.854 vs 0.853, P = 0.965) for the differentiation of HCC from
      nonmalignant CHB, whereas the AUROC of PIVKA-II was significantly better than
      that of AFP in patients with cirrhosis (0.870 vs 0.812, P = 0.042). When PIVKA-II
      and AFP were combined, the diagnostic power improved significantly compared to
      either AFP or PIVKA-II alone for the differentiation of HCC from nonmalignant CHB
      (P < 0.05), especially when cirrhosis was present (P < 0.05). CONCLUSION: Serum
      PIVKA-II might be a better tumor marker than AFP, and its combination with AFP
      may enhance the early detection of HCC in patients with CHB.

PMID- 25852279
TI  - Eradication rate and histological changes after Helicobacter pylori eradication
      treatment in gastric cancer patients following subtotal gastrectomy.
AB  - AIM: To investigate the eradication rate and histological changes after
      Helicobacter pylori (H. pylori) eradication treatment following subtotal
      gastrectomy for gastric cancer. METHODS: A total of 610 patients with H. pylori
      infection who had undergone surgery for either early or advanced gastric
      adenocarcinoma between May 2004 and December 2010 were retrospectively studied. A
      total of 584 patients with proven H. pylori infection after surgery for gastric
      cancer were enrolled in this study. Patients received a seven day standard triple
      regimen as first-line therapy and a 10 d bismuth-containing quadruple regimen as
      second-line therapy in cases of eradication failure. The patients underwent an
      esophagogastroduodenoscopy (EGD) between six and 12 mo after surgery, followed by
      annual EGDs. A further EGD was conducted 12 mo after confirming the result of the
      eradication and the histological changes. A gastric biopsy specimen for
      histological examination and Campylobacter-like organism testing was obtained
      from the lesser and greater curvature of the corpus of the remnant stomach.
      Histological changes in the gastric mucosa were assessed using the updated Sydney
      system before eradication therapy and at follow-up after 12 mo. RESULTS:
      Eradication rates with the first-line and second-line therapies were 78.4%
      (458/584) and 90% (36/40), respectively, by intention-to-treat analysis and 85.3%
      (458/530) and 92.3% (36/39), respectively, by per-protocol analysis. The
      univariate and multivariate analyses revealed that Billroth II surgery was an
      independent factor predictive of eradication success in the eradication success
      group (OR = 1.53, 95%CI: 1.41-1.65, P = 0.021). The atrophy and intestinal
      metaplasia (IM) scores 12 mo after eradication were significantly lower in the
      eradication success group than in the eradication failure group (0.25 +/- 0.04 vs
      0.47 +/- 0.12, P = 0.023; 0.27 +/- 0.04 vs 0.51 +/- 0.12, P = 0.015,
      respectively). The atrophy and IM scores 12 mo after successful eradication were
      significantly lower in the Billroth II group than in the Billroth I group (0.13
      +/- 0.09 vs 0.31 +/- 0.12, P = 0.029; 0.32 +/- 0.24 vs 0.37 +/- 0.13, P = 0.034,
      respectively). CONCLUSION: Patients with H. pylori following subtotal gastrectomy
      had a similar eradication rate to patients with an intact stomach. H. pylori
      eradication is recommended after subtotal gastrectomy.

PMID- 25852280
TI  - Is endoscopic submucosal dissection safe for papillary adenocarcinoma of the
      stomach?
AB  - AIM: To identify the clinicopathological predictors of lymph node (LN) metastasis
      and evaluate the outcomes of endoscopic submucosal dissection (ESD) in papillary
      adenocarcinoma-type early gastric cancers (EGCs). METHODS: From January 2005 to
      May 2013, 49 patients who underwent surgical operation and 24 patients who
      underwent ESD for papillary adenocarcinoma-type EGC were enrolled to identify
      clinicopathological characteristics and predictive factors of LN metastasis and
      to evaluate the outcomes of ESD for papillary adenocarcinoma-type EGC. RESULTS:
      Most papillary adenocarcinoma-type EGCs were located in the lower third of the
      stomach and had an elevated macroscopic shape. The overall prevalence of LN
      metastasis was 18.3% (9/49). The presence of lymphovascular invasion was found to
      be a predictor of LN metastasis (P = 0.016). According to current indication
      criteria of ESD, 6 and 11 of the 49 patients had absolute and expanded
      indications for ESD, respectively. Two patients (11.8%) with expanded indication
      for ESD had LN metastasis. Of the 24 patients who underwent ESD, 13 (54%)
      achieved out-of-ESD indication, with 9 of those 13 patients undergoing surgical
      operation due to non-curative resection. CONCLUSION: The use of ESD should be
      carefully considered for papillary adenocarcinoma-type EGC with suspected ESD
      indication after pre-treatment work-up because of the higher frequency of LN
      metastasis and additional surgeries.

PMID- 25852281
TI  - Differentiation of acute and chronic hepatitis B in IgM anti-HBc positive
      patients.
AB  - AIM: To identify the factors that differentiate acute hepatitis B (AHB) from
      chronic hepatitis B with acute exacerbation (CHB-AE). METHODS: From 2004 to 2013,
      a total of 82 patients (male n = 52, 63.4%; female n = 30, 36.6%) with clinical
      features of acute hepatitis with immunoglobulin M antibodies to the hepatitis B
      core antigen (IgM anti-HBc) were retrospectively enrolled and divided into two
      groups; AHB (n = 53) and CHB-AE (n = 29). The AHB group was defined as patients
      without a history of hepatitis B virus (HBV) infection before the episode and
      with loss of hepatitis B surface antigen within 6 mo after onset of acute
      hepatitis. Biochemical and virological profiles and the sample/cutoff (S/CO)
      ratio of IgM anti-HBc were compared to determine the differential diagnostic
      factors. RESULTS: The multivariate analysis demonstrated that, the S/CO ratio of
      IgM anti-HBc and HBV DNA levels were meaningful factors. The S/CO ratio of IgM
      anti-HBc was significantly higher in the AHB group, while the HBV DNA level was
      significantly higher in the CHB-AE group. The optimal cutoff values of IgM anti
      HBc and HBV DNA levels for differentiating the two conditions were 8 S/CO ratio
      and 5.5 log10 IU/mL, respectively. The sensitivity and specificity were 96.2% and
      89.7% for the S/CO ratio of IgM anti-HBc and 81.1% and 72.4% for HBV DNA levels,
      respectively. The area under receiver operating characteristic curves of both the
      S/CO ratio of IgM anti-HBc and HBV DNA levels were not significantly different
      (0.933 vs 0.844, P = 0.105). When combining IgM anti-HBc and HBV DNA, the
      diagnostic power significantly improved compared to HBV DNA alone (P = 0.0056).
      The combination of these factors yielded a sensitivity and specificity of 98.1%
      and 86.2%, respectively. CONCLUSION: The combination of the S/CO ratio of IgM
      anti-HBc and HBV DNA levels was a useful tool for differentiating AHB from CHB-AE
      in patients with positive IgM anti-HBc.

PMID- 25852282
TI  - Methylation of IRAK3 is a novel prognostic marker in hepatocellular carcinoma.
AB  - AIM: To examine the methylation levels of interleukin-1 receptor-associated
      kinase 3 (IRAK3) and GLOXD1 and their potential clinical applications in
      hepatocellular carcinoma (HCC). METHODS: mRNA expression and promoter methylation
      of IRAK3 and GLOXD1 in HCC cells were analyzed by reverse transcription
      polymerase chain reaction (RT-PCR) and methylation-specific PCR (MSP),
      respectively. Using pyrosequencing results, we further established a quantitative
      MSP (Q-MSP) system for the evaluation of IRAK3 and GLOXD1 methylation in 29
      normal controls and 160 paired HCC tissues and their adjacent nontumor tissues.
      We also calculated Kaplan-Meier survival curves to determine the applications of
      gene methylation in the prognosis of HCC. RESULTS: IRAK3 and GLOXD1 expression
      was partially restored in several HCC cell lines after treatment with 5-aza-2'
      deoxycytidine (DNA methyltransferase inhibitor; 5DAC). A partial decrease in the
      methylated band was also observed in the HCC cell lines after 5DAC treatment.
      Using GLOXD1 as an example, we found a significant correlation between the data
      obtained from the methylation array and from pyrosequencing. The methylation
      frequency of IRAK3 and GLOXD1 in HCC tissues was 46.9% and 63.8%, respectively.
      Methylation of IRAK3 was statistically associated with tumor stage. Moreover, HCC
      patients with IRAK3 methylation had a trend toward poor 3-year disease-free
      survival (P < 0.05). CONCLUSION: IRAK3 and GLOXD1 were frequently methylated in
      HCC tissues compared to normal controls and nontumor tissues. IRAK3 methylation
      was associated with tumor stage and poor prognosis of patients. These data
      suggest that IRAK3 methylation is a novel prognostic marker in HCC.

PMID- 25852284
TI  - Endoscopic transpancreatic septotomy as a precutting technique for difficult bile
      duct cannulation.
AB  - AIM: To evaluate the technique of transpancreatic septotomy (TS) for cannulating
      inaccessible common bile ducts in endoscopic retrograde cholangiopancreatography
      (ERCP). METHODS: Between May 2012 and April 2013, 1074 patients were referred to
      our department for ERCP. We excluded 15 patients with previous Billroth II
      gastrectomy, Roux-en-Y anastomosis, duodenal stenosis, or duodenal papilla tumor.
      Among 1059 patients who underwent ERCP, there were 163 patients with difficult
      bile duct cannulation. Pancreatic guidewire or pancreatic duct plastic stent
      assistance allowed for successful ERCP completion in 94 patients. We
      retrospectively analyzed clinical data from 69 failed patients (36
      transpancreatic septotomies and 33 needle-knife sphincterotomies). RESULTS: Of
      the 69 patients who underwent precut papillotomy, common bile duct cannulation
      was successfully achieved in 67. The success rates in the TS and needle knife
      sphincterotomy (NKS) groups were 97.2% (35/36) and 96.9% (32/33), respectively,
      which were not significantly different (P > 0.05). Complications occurred in 11
      cases, including acute pancreatitis (n = 6), bleeding (n = 2), and cholangitis (n
      = 3). The total frequency of complications in the TS group was lower than that in
      the NKS group (8.3% vs 24.2%, P < 0.05). CONCLUSION: Pancreatic guidewire or
      pancreatic duct plastic stent assistance improves the success rate of selective
      bile duct cannulation in ERCP. TS and NKS markedly improve the success rate of
      selective bile duct cannulation in ERCP. TS precut is safer as compared with NKS.

PMID- 25852283
TI  - Oxaliplatin and 5-fluorouracil hepatic infusion with lipiodolized
      chemoembolization in large hepatocellular carcinoma.
AB  - AIM: To investigate transarterial chemoembolization (TACE) with hepatic infusion
      of oxaliplatin and 5-fluorouracil and Lipiodol chemoembolization in large
      hepatocellular carcinoma (HCC). METHODS: In this retrospective study, 132
      patients with unresectable HCCs larger than 10 cm were treated with hepatic
      infusion of oxaliplatin and 5-fluorouracil followed by Lipiodol
      chemoembolization. The primary endpoint was overall survival (OS). Sixteen-week
      disease-control rate, time to progression (TTP), and major complications were
      also studied. Univariate and multivariate analyses were performed to identify
      prognostic factors affecting OS and TTP. RESULTS: A total of 319 procedures were
      performed in the 132 patients. Eleven (8.3%) patients received radical resection
      following TACE treatment (median time to initial TACE 4.3 +/- 2.3 mo). The median
      OS and TTP were 10.3 and 3.0 mo respectively, with a 50.0% 16-wk disease-control
      rate. Major complications were encountered in 6.0% (8/132) of patients following
      TACE and included serious jaundice in 1.5% (2/132) patients, aleukia in 1.5%
      (2/132), and hepatic failure in 3.0% (4/132). One patient died within one month
      due to serious hepatic failure and severe sepsis after receiving the second TACE.
      The risk factor associated with TTP was baseline alpha-fetoprotein level, and
      vascular invasion was an independent factor related to OS. CONCLUSION: Hepatic
      infusion of oxaliplatin and 5-fluorouracil followed by lipiodolized
      chemoembolization is a safe and promising treatment for patients with HCCs larger
      than 10 cm in diameter.

PMID- 25852285
TI  - Decreased STAT4 indicates poor prognosis and enhanced cell proliferation in
      hepatocellular carcinoma.
AB  - AIM: To investigate the role of signal transduction and activation of
      transcription 4 (STAT4) in the development and progression of human
      hepatocellular carcinoma (HCC). METHODS: Recent genetic investigations have
      identified that a genetic variant of STAT4 is associated with hepatitis B virus
      (HBV)-related HCC. The level of STAT4 in 90 HCC patients was examined via Western
      blot and immunohistochemical analyses. The correlation between STAT4 expression
      and the clinicopathological characteristics of the patients was analyzed. The
      level of STAT4 expression in the HCC liver tissues was significantly lower than
      that in the non-HCC liver tissues and correlated with tumor size, histological
      grade of HCC and serum hepatitis B surface antigen level in HCC patients. The
      data were statistically analyzed using SPSS. Furthermore, siRNA oligos targeting
      STAT4 were employed to investigate the influence of STAT4 RNA interference on HCC
      cell physiology. Based on Cell Counting Kit-8 and flow cytometric assays, we
      found that depletion of STAT4 expression significantly enhanced the proliferation
      of L02 cells. RESULTS: STAT4 protein expression was significantly lower in HCC
      tissues than in normal liver tissues. Immunohistochemistry followed by
      statistical analysis revealed that the expression of STAT4 negatively correlated
      with Ki67 expression (r = 0.851; P < 0.05) and positively correlated with maximal
      tumor size (P < 0.05), HBV (P = 0.012) and histological grade (P < 0.05). Kaplan
      Meier analysis revealed significant differences in the survival curves between
      HCC patients expressing low and high levels of STAT4 and Ki67 (P < 0.05). Based
      on a multivariate Cox proportional hazard model, STAT4 expression was an
      independent prognostic indicator for HCC patients who underwent curative
      resection. In vitro, following the release of L02 cell lines from serum
      starvation, the expression of STAT4 was downregulated, and transfection of L02
      cells with siRNA targeting STAT4 inhibited cell proliferation. CONCLUSION: Our
      data indicate that STAT4 may inhibit HCC development by modulating HCC cell
      proliferation.

PMID- 25852286
TI  - Importance of reporting segmental bowel preparation scores during colonoscopy in
      clinical practice.
AB  - AIM: To evaluate the impact of reporting bowel preparation using Boston Bowel
      Preparation Scale (BBPS) in clinical practice. METHODS: The study was a
      prospective observational cohort study which enrolled subjects reporting for
      screening colonoscopy. All subjects received a gallon of polyethylene glycol as
      bowel preparation regimen. After colonoscopy the endoscopists determined quality
      of bowel preparation using BBPS. Segmental scores were combined to calculate
      composite BBPS. Site and size of the polyps detected was recorded. Pathology
      reports were reviewed to determine advanced adenoma detection rates (AADR).
      Segmental AADR's were calculated and categorized based on the segmental BBPS to
      determine the differential impact of bowel prep on AADR. RESULTS: Three hundred
      and sixty subjects were enrolled in the study with a mean age of 59.2 years,
      36.3% males and 63.8% females. Four subjects with incomplete colonoscopy due BBPS
      of 0 in any segment were excluded. Based on composite BBPS subjects were divided
      into 3 groups; Group-0 (poor bowel prep, BBPS 0-3) n = 26 (7.3%), Group-1
      (Suboptimal bowel prep, BBPS 4-6) n = 121 (34%) and Group-2 (Adequate bowel prep,
      BBPS 7-9) n = 209 (58.7%). AADR showed a linear trend through Group-1 to 3; with
      an AADR of 3.8%, 14.8% and 16.7% respectively. Also seen was a linear increasing
      trend in segmental AADR with improvement in segmental BBPS. There was statistical
      significant difference between AADR among Group 0 and 2 (3.8% vs 16.7%, P <
      0.05), Group 1 and 2 (14.8% vs 16.7%, P < 0.05) and Group 0 and 1 (3.8% vs 14.8%,
      P < 0.05). chi(2) method was used to compute P value for determining statistical
      significance. CONCLUSION: Segmental AADRs correlate with segmental BBPS. It is
      thus valuable to report segmental BBPS in colonoscopy reports in clinical
      practice.

PMID- 25852287
TI  - Rectal tone and compliance affected in patients with fecal incontinence after
      fistulotomy.
AB  - AIM: To investigate the anal sphincter and rectal factors that may be involved in
      fecal incontinence that develops following fistulotomy (FIAF). METHODS: Eleven
      patients with FIAF were compared with 11 patients with idiopathic fecal
      incontinence and with 11 asymptomatic healthy subjects (HS). All of the study
      participants underwent anorectal manometry and a barostat study (rectal
      sensitivity, tone, compliance and capacity). The mean time since surgery was 28
      +/- 26 mo. The postoperative continence score was 14 +/- 2.5 (95%CI: 12.4-15.5,
      St Mark's fecal incontinence grading system). RESULTS: Compared with the HS, the
      FIAF patients showed increased rectal tone (42.63 +/- 27.69 vs 103.5 +/- 51.13, P
      = 0.002) and less rectal compliance (4.95 +/- 3.43 vs 11.77 +/- 6.9, P = 0.009).
      No significant differences were found between the FIAF patients and the HS with
      respect to the rectal capacity; thresholds for the non-noxious stimuli of first
      sensation, gas sensation and urge-to-defecate sensation or the noxious stimulus
      of pain; anal resting pressure or squeeze pressure; or the frequency or
      percentage of relaxation of the rectoanal inhibitory reflex. No significant
      differences were found between the FIAF patients and the patients with idiopathic
      fecal incontinence. CONCLUSION: In patients with FIAF, normal motor anal
      sphincter function and rectal sensitivity are preserved, but rectal tone and
      compliance are impaired. The results suggest that FIAF is not due to alterations
      in rectal sensitivity and that the rectum is more involved than the anal
      sphincters in the genesis of FIAF.

PMID- 25852288
TI  - Interferon-lambda-related genes and therapeutic response in Chinese hepatitis C
      patients.
AB  - AIM: To determine the association between rapid viral response and IL28B, IL28RA,
      IL10RB and MxA polymorphisms in the Chinese Han population. METHODS: The study
      cohort consisted of 238 chronic hepatitis C patients treated with interferon
      (IFN)-alpha-2b and ribavirin. Six single nucleotide polymorphisms were genotyped
      using the ABI TaqMan allelic discrimination assay. Biochemical indices were
      measured at baseline. Serum hepatitis C virus (HCV) RNA was detected at weeks 0,
      4, 12 and 24 of therapy. RESULTS: Only IL28B rs12980275 was associated with
      treatment response in the Chinese Han population. Patients carrying AG/GG
      genotypes had a reduced rapid viral response compared with patients carrying the
      AA genotype (additive model: adjusted OR = 0.43, 95%CI: 0.24-0.75). It took less
      time for patients with the AA genotype to achieve a viral load < 500 copies/mL
      (log-rank test, P = 0.004). In addition, the protective effect of genotype AA was
      independent of baseline viral load. HCV genotype, and baseline white blood cell
      count, alpha-fetoprotein and viral load might also help predict treatment
      response. The area under the receiver-operating characteristic curve was 0.726.
      CONCLUSION: IL28B rs12980275 AA genotype is a strong predictor of positive
      response to IFN therapy in Chinese Han patients with hepatitis C.

PMID- 25852289
TI  - Endoscopic ultrasound elastography strain histograms in the evaluation of
      patients with pancreatic masses.
AB  - AIM: To investigate the accuracy of the strain histogram endoscopic ultrasound
      (EUS)-based method for the diagnostic differentiation of patients with pancreatic
      masses. METHODS: In a prospective single center study, 149 patients were
      analyzed, 105 with pancreatic masses and 44 controls. Elastography images were
      recorded using commercially available ultrasound equipment in combination with
      EUS linear probes. Strain histograms (SHs) were calculated by machine integrated
      software in regions of interest and mean values of the strain histograms were
      expressed as Mode 1 (over the mass) and Mode 2 (over an adjacent part of
      pancreatic tissue, representing the reference area). The ratio between Mode 2 and
      Mode 1 was calculated later, representing a new variable, the strain histogram
      ratio. After the final diagnosis was established, two groups of patients were
      formed: a pancreatic cancer group with positive cytology achieved by fine needle
      aspiration puncture or histology after surgery (58 patients), and a mass-forming
      pancreatitis group with negative cytology and follow-up after 3 and 6 mo (47
      patients). All statistical analyses were conducted in SPSS 14.0 (SPSS Inc.,
      Chicago, IL, United States). RESULTS: Results were obtained with software for
      strain histograms with reversed hue scale (0 represents the hardest tissue
      structure and 255 the softest). Based on the receiver operating characteristics
      (ROC) curve coordinates, the cut-off point for Mode 1 was set at the value of 86.
      Values under the cut-off point indicated the presence of pancreatic malignancy.
      Mode 1 reached 100% sensitivity and 45% specificity with overall accuracy of 66%
      (95%CI: 61%-66%) in detection of pancreatic malignant tumors among the patients
      with pancreatic masses. The positive and negative predictive values were 54% and
      100%, respectively. The cut-off for the new calculated variable, the SH ratio,
      was set at the value 1.153 based on the ROC curve coordinates. Values equal or
      above the cut-off value were indicative of pancreatic malignancy. The SH ratio
      reached 98% sensitivity, 50% specificity and an overall accuracy of 69% (95%CI:
      63%-70%). The positive and negative predictive values were 92% and 100%,
      respectively. CONCLUSION: SH showed high sensitivity in pancreatic malignant
      tumor detection but disappointingly low specificity. Slight improvements in
      specificity and accuracy were achieved using the SH ratio.

PMID- 25852290
TI  - PERFACT procedure: a new concept to treat highly complex anal fistula.
AB  - AIM: To check the efficacy of the PERFACT procedure in highly complex fistula-in
      ano. METHODS: The PERFACT procedure (proximal superficial cauterization, emptying
      regularly fistula tracts and curettage of tracts) entails two steps: superficial
      cauterization of mucosa at and around the internal opening and keeping all the
      tracts clean. The principle is to permanently close the internal opening by
      granulation tissue. This is achieved by superficial electrocauterization at and
      around the internal opening and subsequently allowing the wound to heal by
      secondary intention. Along with this, all the tracts are curetted and it is
      ensured that they remain empty and clean in the postoperative period until they
      heal completely. The latter step also facilitates the closure of the internal
      opening by preventing collected fluid in the tracts from entering the internal
      opening and thus not letting it close. Objective incontinence scoring was done
      preoperatively and 3 mo after the operation. RESULTS: Fifty-one patients with
      complex fistula-in-ano were prospectively enrolled. The median follow-up was 9 mo
      (5-14 mo). The mean age was 42.7 +/- 11.3 years. Male:female ratio was 43:8.
      Fistula was recurrent in 76.5% (39/51), horseshoe in 50.1% (26/51), had multiple
      tracts in 52.9% (27/51), had an associated abscess in 41.2% (21/51), was anterior
      in 33.3% (17/51), the internal opening was not found in 15.7% (8/51) and 9.8%
      (5/51) of fistulas had a supralevator extension. Seven patients were excluded (5
      lost to follow up, 2 with tuberculosis leading to/associated with fistula-in
      ano). The success rate was 79.5% (35/44) and the recurrence rate was 20.5%
      (9/44). Out of these recurrences, three underwent reoperation (2 PERFACT
      procedure, 1 fistulotomy) and all three were successful. Thus, the overall
      success rate was 86.4%. The only complication was a non-healing tract in 9.1%
      (4/44) of patients. There was no significant change in objective incontinence
      scores three months after the operation. The pain was minimal, with all patients
      resuming their normal activities within 72 h of the operation. CONCLUSION: The
      PERFACT procedure is a new effective method for complex fistula-in-ano, effective
      even in fistula associated with abscess, supralevator fistula-in-ano and where
      the internal opening is non-localizable.

PMID- 25852291
TI  - Lower gastrointestinal bleeding: role of 64-row computed tomographic angiography
      in diagnosis and therapeutic planning.
AB  - AIM: To determine the value of computed tomographic angiography (CTA) for
      diagnosis and therapeutic planning in lower gastrointestinal (GI) bleeding.
      METHODS: Sixty-three consecutive patients with acute lower GI bleeding underwent
      CTA before endovascular or surgical treatment. CTA was used to determine whether
      the lower GI bleeding was suitable for endovascular treatment, surgical
      resection, or conservative treatment in each patient. Treatment planning with CTA
      was compared with actual treatment decisions or endovascular or surgical
      treatment that had been carried out in each patient based on CTA findings.
      RESULTS: 64-row CTA detected active extravasation of contrast material in 57
      patients and six patients had no demonstrable active bleeding, resulting in an
      accuracy of 90.5% in the detection of acute GI bleeding (57 of 63). In three of
      the six patients with no demonstrable active bleeding, active lower GI bleeding
      recurred within one week after CTA, and angiography revealed acute bleeding. The
      overall location-based accuracy, sensitivity, specificity, positive predictive
      value (PPV) and negative predictive value (NPV) for the detection of GI bleeding
      by 64-row CTA were 98.8% (249 of 252), 95.0% (57 of 60), 100% (192 of 192), 100%
      (57 of 57), and 98.5% (192 of 195), respectively. Treatment planning was
      correctly established on the basis of 64-row CTA with an accuracy, sensitivity,
      specificity, PPV and NPV of 98.4% (248 of 252), 93.3% (56 of 60), 100% (192 of
      192), 100% (56 of 56), and 97.5% (192 of 196), respectively, in a location-based
      evaluation. CONCLUSION: 64-row CTA is safe and effective in making decisions
      regarding treatment, without performing digital subtraction angiography or
      surgery, in the majority of patients with lower GI bleeding.

PMID- 25852292
TI  - Osteoporosis and bone fractures in alcoholic liver disease: a meta-analysis.
AB  - AIM: To evaluate the association between alcoholic liver disease (ALD) and bone
      fractures or osteoporosis. METHODS: Non-randomized studies were identified from
      databases (PubMed, EMBASE, and the Cochrane Library). The search was conducted
      using Boolean operators and keywords, which included "alcoholic liver diseases",
      "osteoporosis", or "bone fractures". The prevalence of any fractures or
      osteoporosis, and bone mineral density (BMD) were extracted and analyzed using
      risk ratios and standardized mean difference (SMD). A random effects model was
      applied. RESULTS: In total, 15 studies were identified and analyzed. Overall, ALD
      demonstrated a RR of 1.944 (95%CI: 1.354-2.791) for the development of bone
      fractures. However, ALD showed a RR of 0.849 (95%CI: 0.523-1.380) for the
      development of osteoporosis. BMD was not significantly different between the ALD
      and control groups, although there was a trend toward lower BMD in patients with
      ALD (SMD in femur-BMD: -0.172, 95%CI: -0.453-0.110; SMD in spine-BMD: -0.169,
      95%CI: -0.476-0.138). Sensitivity analyses showed consistent results. CONCLUSION:
      Current publications indicate significant associations between bone fractures and
      ALD, independent of BMD or the presence of osteoporosis.

PMID- 25852294
TI  - Urea cycle disorders: a case report of a successful treatment with liver
      transplant and a literature review.
AB  - The urea cycle is the final pathway for nitrogen metabolism. Urea cycle disorders
      (UCDs) include a variety of genetic defects, which lead to inefficient urea
      synthesis. Elevated blood ammonium level is usually dominant in the clinical
      pattern and the primary manifestations affect the central nervous system. Herein,
      we report the case of a 17-year-old girl who was diagnosed with UCD at the age of
      3. Despite a controlled diet, she was hospitalized several times for acute
      attacks with recurrent life risk. She came to our attention for a hyperammonemic
      episode. We proposed an orthotopic liver transplant (OLT) as a treatment; the
      patient and her family were in complete agreement. On February 28, 2007, she
      successfully received a transplant. Following the surgery, she has remained well,
      and she is currently leading a normal life. Usually for UCDs diet plays the
      primary therapeutic role, while OLT is often considered as a last resort. Our
      case report and the recent literature data on the quality of life and prognosis
      of traditionally treated patients vs OLT patients, support OLT as a primary
      intervention to prevent life-threatening acute episodes and chronic mental
      impairment. 

PMID- 25852293
TI  - Resolution of Crohn's disease and complex regional pain syndrome following
      treatment of paratuberculosis.
AB  - A cohort of family members with various chronic diseases including Crohn's
      disease, asthma, complex regional pain syndrome, hypothyroidism, type 1 diabetes
      mellitus, and lymphangiomatosis and/or evidence of infection by Mycobacterium
      avium subsp. paratuberculosis (MAP) are described in this series of case reports.
      MAP was cultured from the blood of three members affected by the first five
      diseases and there was accompanying elevated anti-MAP IgG in two members. The
      patient affected by the sixth disease has a markedly elevated anti-MAP titer. The
      two patients affected by the first four diseases have been treated with a
      combination of anti-MAP antibiotics and ultraviolet blood irradiation therapy
      with resolution of the disease symptomatology and inability to culture MAP in
      post treatment blood samples. These case reports of patients with MAP infections
      provide supportive evidence of a pathogenic role of MAP in humans. 

PMID- 25852296
TI  - Treatment of Crohn's disease and familial Mediterranean fever by leukopheresis:
      single shot for two targets.
AB  - Coexistence of Crohn's disease (CD) and familial Mediterranean fever (FMF) is a
      rare condition and knowledge about this clinical situation is limited with a few
      case reports in the literature. The treatment of both diseases depends on their
      individual therapies. However, it is very hard to deal with this coexistence when
      CD is refractory to standard therapies. Ongoing activity of CD triggers the
      clinical attacks of FMF and the symptoms like abdominal pain interfere with both
      disease presentations which can cause problems about diagnostic and therapeutic
      approach. The main therapeutic agent for FMF is colchicine and diarrhea is the
      most common side effect of this drug. This side effect also causes problems about
      management of these diseases when both of them are clinically active. Here we
      report probably the first case in the literature with coexisting CD and FMF who
      was successfully treated by leukopheresis since he was refractory to conventional
      therapies for CD. 

PMID- 25852295
TI  - Gastroenterology case report of mesalazine-induced cardiopulmonary
      hypersensitivity.
AB  - Mesalazine is a 5-aminosalicylic acid derivative that has been widely used to
      treat patients with inflammatory bowel disease. Accumulating evidence indicates
      that mesalazine has a very low rate of adverse drug reactions and is well
      tolerated by patients. However, a few cases of pulmonary and cardiac disease
      related to mesalazine have been reported in the past, though infrequently,
      preventing clinicians from diagnosing the conditions early. We describe the case
      of a 32-year-old man with ulcerative colitis who was admitted with a two-month
      history of persistent fever following mesalazine treatment initiated 14 mo
      earlier. At the time of admission, mesalazine dose was increased from 1.5 to 3.0
      g/d, and antibiotic therapy was started with no improvement. Three weeks after
      admission, the patient developed dyspnea, non-productive cough, and chest pain.
      Severe eosinophilia was detected in laboratory tests, and a computed tomography
      scan revealed interstitial infiltrates in both lungs, as well as a large
      pericardial effusion. The bronchoalveolar lavage reported a CD4/CD8 ratio of 0.5,
      and an increased eosinophil count. Transbronchial biopsy examination showed a
      severe eosinophilic infiltrate of the lung tissue. Mesalazine-induced
      cardiopulmonary hypersensitivity was suspected after excluding other possible
      etiologies. Consequently, mesalazine treatment was suspended, and corticosteroid
      therapy was initiated, resulting in resolution of symptoms and radiologic
      abnormalities. We conclude that mesalazine-induced pulmonary and cardiac
      hypersensitivity should always be considered in the differential diagnosis of
      unexplained cardiopulmonary symptoms and radiographic abnormalities in patients
      with inflammatory bowel disease. 

PMID- 25852297
TI  - Adenocarcinoma arising from heterotopic pancreas at the third portion of the
      duodenum.
AB  - A 62-year-old Japanese man presented to our hospital with a history of weight
      loss of 6 kg in 4 mo. Imaging examinations revealed a tumor located on the third
      portion of the duodenum with stenosis. We suspected duodenal carcinoma and
      performed pancreas-preserving segmental duodenectomy. Adenocarcinoma arising from
      a heterotopic pancreas at the third portion of the duodenum was finally diagnosed
      by immunohistochemical staining. Malignant transformation in the duodenum arising
      from a heterotopic pancreas is extremely rare; to our knowledge, only 13 cases
      have been reported worldwide, including the present case. The most common
      location of malignancy is the proximal duodenum at the first and descending
      portion. Herein, we describe the first case of adenocarcinoma arising from a
      heterotopic pancreas, which was located in the third portion of the duodenum,
      with a review of the literature. 

PMID- 25852298
TI  - Lymphoepithelioma-like cholangiocarcinoma: a mimic of hepatocellular carcinoma on
      imaging features.
AB  - Primary lymphoepithelioma-like carcinoma in the liver is extremely rare. A few
      cases of lymphoepithelioma-like cholangiocarcinoma have been reported, but few
      radiologic features were described. We reviewed 23 cases of lymphoepithelioma
      like cholangiocarcinoma reported between 1996 and 2014 and describe a rare case
      of a 35-year-old woman in our hospital who was diagnosed with lymphoepithelioma
      like cholangiocarcinoma of the liver and was a hepatitis B carrier. The tumor
      (1.6 cm) in our patient appeared to be hypoechoic in sonographic images and
      hypodense in computed tomography (CT) images. In addition, it was homogeneous
      hypointense in T1-weighted magnetic resonance (MR) images (MRI) and hyperintense
      in T2-weighted MRI. Dynamic gadolinium-enhanced MRI showed typical image pattern
      of hepatocellular carcinoma (HCC). The patient underwent a laparoscopic left
      hepatic lobectomy, and the resected tumor consisted of well-differentiated
      glandular cells with extensive lymphocytic infiltration that were immunoreactive
      to CK (AE1/AE3), CD3, and CD20. In addition, the tumor was positive for Epstein
      Barr virus-encoded RNA in situ hybridization. Finally, lymphoepithelioma-like
      cholangiocarcinoma was diagnosed. In previous studies, the incidence is highest
      among middle-aged people. Most tumors appeared to be hypodense with either
      hypovascular or hypervascular patterns in CT images. This case report is the
      first study to address sonography, CT, and MRI observations and delineate
      pathologic correlations. We suggest that the imaging pattern of lymphoepithelioma
      like cholangiocarcinoma, either the typical cholangiocarcinoma pattern or a mimic
      of HCC, should be considered in the differential lists for HCC. 

PMID- 25852299
TI  - Segmental small bowel necrosis associated with antiphospholipid syndrome: a case
      report.
AB  - Antiphospholipid syndrome is a multi-system disease characterized by the
      formation of thromboembolic complications and/or pregnancy morbidity, and with
      persistently increased titers of antiphospholipid antibodies. We report the case
      of a 50-year-old, previously healthy man who presented with fever and new-onset,
      dull abdominal pain. A contrast-enhanced computed tomography scan showed
      segmental small bowel obstruction, for which an emergency laparotomy was
      performed. Histopathologic examination of resected tissues revealed multiple
      intestinal and mesenteric thromboses of small vessels. Laboratory tests for serum
      antiphospholipid (anticardiolipin IgM) and anti-beta2-glycoprotein I antibodies
      were positive. Despite proactive implementation of anticoagulation, steroid, and
      antibiotic therapies, the patient's condition rapidly deteriorated, and he died
      22 d after admission. This case highlights that antiphospholipid syndrome should
      be suspected in patients with unexplainable ischemic bowel and intestinal
      necrosis presenting with insidious clinical features that may be secondary to the
      disease, as early diagnosis is critical to implement timely treatments in order
      to ameliorate the disease course. 

PMID- 25852300
TI  - Lower folate levels in gastric cancer: is it a cause or a result?
AB  - Folate deficiency and its association with cancer have been studied in the
      literature, but its clinical impact is still unknown. Folate deficiency and its
      result on gastric cancer is a mysterious part of oncology, with ongoing studies
      hopefully clarifying its impact on gastric cancer management. Lee et al studied
      folate deficiency and its impact on staging and clinical results. Here we try to
      contribute to the field by expressing our own thoughts about the paper. 

PMID- 25852301
TI  - Temporal trends and current practice patterns for intraoperative ventilation at
      U.S. academic medical centers: a retrospective study.
AB  - BACKGROUND: Lung protective ventilation strategies utilizing lower tidal volumes
      per predicted body weight (PBW) and positive end-expiratory pressure (PEEP) have
      been suggested to be beneficial in a variety of surgical populations. Recent
      clinical studies have used control groups ventilated with high tidal volumes
      without PEEP based on the assumption that this reflects current clinical
      practice. We hypothesized that ventilation strategies have changed over time,
      that most anesthetics in U.S. academic medical centers are currently performed
      with lower tidal volumes, and that most receive PEEP. METHODS: Intraoperative
      data were pooled for adults undergoing general anesthesia with tracheal
      intubation. Median tidal volumes per kilogram of PBW were categorized as > 10, 8
      10 and < 8 mL per kg of PBW. The percentages of cases in 2013 that were performed
      with median tidal volumes < 8 mL per kg of PBW and PEEP were determined. As a
      secondary analysis, a proportional odds model using institution, year, height,
      weight and gender determined the relative associations of these factors using
      categorical and interquartile odds ratios. RESULTS: 295,540 cases were analyzed
      from 5 institutions over a period of 10 years. In 2013, 59.3% of cases used
      median tidal volumes < 8 mL per kg of PBW, 83.3% used PEEP, and 51.0% used both.
      Of those cases with PEEP, 60.9% used a median pressure of >= 5 cmH2O. Predictors
      of lower categories of tidal volumes included height (odds ratio (OR) 10.83, 95%
      confidence interval [10.50, 11.16]), institution (lowest OR 0.98 [0.96, 1.00],
      highest OR 9.63 [9.41, 9.86]), year (lowest OR 1.32 [1.21, 1.44], highest OR 6.31
      [5.84, 6.82]), male gender (OR 1.10 [1.07, 1.12]), and weight (OR 0.30 [0.29,
      0.31]). CONCLUSION: Most general anesthetics with tracheal intubation at the
      institutions surveyed are currently performed with a median tidal volume < 8 mL
      per kg of PBW, most are managed with PEEP of >= 5 cmH2O and approximately half
      utilize both. Given the diversity of the institutions included, this is likely
      reflective of practice in U.S. academic medical centers. The utilization of
      higher tidal volumes without PEEP in control groups for clinical research studies
      should be reconsidered.

PMID- 25852302
TI  - Bim and VDAC1 are hierarchically essential for mitochondrial ATF2 mediated cell
      death.
AB  - BACKGROUND: ATF2 mediated cytochrome c release is the formation of a channel with
      some unknown factors larger than that of the individual proteins. BHS-only
      proteins (BH3s), such as Bim, could induce BAX and VDAC, forming a new channel.
      According to this facts, we can speculated that there is possible signal
      relationship with BH3s and ATF2, which is associated with mitochondrial-based
      death programs. METHODS: The growth inhibitory effects of mitochondrial ATF2 were
      tested in cancer cell lines B16F10, A549, EG7, and LL2. Apoptosis was measured by
      flow cytometry. The effects of ATF2 and levels of apoptosis regulatory proteins
      were measured by Western blotting. The interaction of proteins were evaluated by
      immunoprecipitation analysis. The in vivo antitumor activity of mitochondrial
      ATF2 were tested in xenograft B16F10 models. RESULTS: Genotoxic stress enabled
      mitochondrial ATF2 accumulation, perturbing the HK1-VDAC1 complex, increasing
      mitochondrial permeability, and promoting apoptosis. ATF2 inhibition strongly
      reduced the conformational activation of Bim, suggesting that Bim acts downstream
      of ATF2. Although Bim downregulation had no effect on ATF2 activation, Bim
      knockdown abolished VDAC1 activation; the failure of VDAC1 activation in Bim
      depleted cells could be reversed by the BH3-only protein mimic ABT-737. We also
      demonstrate that silencing of ATF2 in B16F10 cells increases both the incidence
      and prevalence of tumor xenografts in vivo, whereas stably mitochondrial ATF2
      transfection inhibited B16F10 tumor xenografts growth. CONCLUSIONS: Altogether,
      these results show that ATF2 is a component of the apoptosis machinery that
      involves a hierarchical contribution of ATF2, Bim, and VDAC1. Our data offer new
      insight into the mechanism of mitochondrial ATF2 in mitochondrial apoptosis.

PMID- 25852304
TI  - Propargylic substitution reactions with various nucleophilic compounds using
      efficient and recyclable mesoporous silica spheres embedded with FeCo/graphitic
      shell nanocrystals.
AB  - Phosphomolybdic acid (PMA, H3PMo12O40) functioned as a catalyst for reactions of
      secondary propargylic alcohols and nucleophiles. Highly stable and magnetically
      recyclable mesoporous silica spheres (MMS) embedded with FeCo-graphitic carbon
      shell nanocrystals (FeCo/GC@MSS) were fabricated by a modified Stober process and
      chemical vapor deposition (CVD) method. The FeCo/GC@MSS were loaded with
      phosphomolybdic acid (PMA@FeCo/GC@MSS), and their catalytic activity was
      investigated. Propargylic reactions of 1,3-diphenyl-2-propyn-1-ol with a wide
      range of nucleophiles bearing activating substituents were catalyzed under mild
      conditions. It was found that the MMS possess mesoporosities and have enough
      inner space to load FeCo and phosphomolybdic acid. The FeCo/GC@MSS were found to
      be chemically stable against acid etching and oxidation. This suggests that the
      nanocrystals can be used as a support for an acid catalyst. Moreover, the
      magnetic property of the nanocrystals enabled the facile separation of catalysts
      from the products. 

PMID- 25852303
TI  - Differential effects of dopamine signalling on long-term memory formation and
      consolidation in rodent brain.
AB  - BACKGROUND: Using auditory discrimination learning in gerbils, we have previously
      shown that activation of auditory-cortical D1/D5 dopamine receptors facilitates
      mTOR-mediated, protein synthesis-dependent mechanisms of memory consolidation and
      anterograde memory formation. To understand molecular mechanisms of this
      facilitatory effect, we tested the impact of local pharmacological activation of
      different D1/D5 dopamine receptor signalling modes in the auditory cortex. To
      this end, protein patterns in soluble and synaptic protein-enriched fractions
      from cortical, hippocampal and striatal brain regions of ligand- and vehicle
      treated gerbils were analysed by 2D gel electrophoresis and mass spectrometry 24
      h after intervention. RESULTS: After auditory-cortical injection of SKF38393 - a
      D1/D5 dopamine receptor-selective agonist reported to activate the downstream
      effectors adenylyl cyclase and phospholipase C - prominent proteomic alterations
      compared to vehicle-treated controls appeared in the auditory cortex, striatum,
      and hippocampus, whereas only minor changes were detectable in the frontal
      cortex. In contrast, auditory-cortical injection of SKF83959 - a D1/D5 agonist
      reported to preferentially stimulate phospholipase C - induced pronounced changes
      in the frontal cortex. At the molecular level, we detected altered regulation of
      cytoskeletal and scaffolding proteins, changes in proteins with functions in
      energy metabolism, local protein synthesis, and synaptic signalling.
      Interestingly, abundance and/or subcellular localisation of the predominantly
      presynaptic protein alpha-synuclein displayed dopaminergic regulation. To assess
      the role of alpha-synuclein for dopaminergic mechanisms of memory modulation, we
      tested the impact of post-conditioning systemic pharmacological activation of
      different D1/D5 dopamine receptor signalling modes on auditory discrimination
      learning in alpha-synuclein-mutant mice. In C57BL/6JOlaHsd mice, bearing a
      spontaneous deletion of the alpha-synuclein-encoding gene, but not in the related
      substrains C57BL/6JCrl and C57BL/6JRccHsd, adenylyl cyclase-mediated signalling
      affected acquisition rates over future learning episodes, whereas phospholipase C
      mediated signalling affected final memory performance. CONCLUSIONS: Dopamine
      signalling modes via D1/D5 receptors in the auditory cortex differentially impact
      protein profiles related to rearrangement of cytomatrices, energy metabolism, and
      synaptic neurotransmission in cortical, hippocampal, and basal brain structures.
      Altered dopamine neurotransmission in alpha-synuclein-deficient mice revealed
      that distinct D1/D5 receptor signalling modes may control different aspects of
      memory consolidation.

PMID- 25852305
TI  - Targeted images of KB cells using folate-conjugated gold nanoparticles.
AB  - Mercaptosuccinic acid-coated gold (GM) nanoparticles were prepared and
      characterized by transmission electron microscopy and dynamic light scattering.
      Folic acid (F) was then conjugated to the GM to preferentially target oral
      squamous cancer (KB) cells with folate receptors expressed on their membranes and
      facilitate the transit of the nanoparticles across the cell membrane. Finally, a
      fluorescence dye (Atto) was conjugated to the nanoparticles to visualize their
      internalization into KB cells. After culture of the cells in a medium containing
      GM and folate-conjugated GM (GF), the interaction of surface-modified gold
      nanoparticles with KB cells was studied. 

PMID- 25852306
TI  - High electron mobility and low carrier concentration of hydrothermally grown ZnO
      thin films on seeded a-plane sapphire at low temperature.
AB  - Hydrothermal zinc oxide (ZnO) thick films were successfully grown on the chemical
      vapor deposition (CVD)-grown thick ZnO seed layers on a-plane sapphire substrates
      using the aqueous solution of zinc nitrate dehydrate (Zn(NO3)2). The use of the
      CVD ZnO seed layers with the flat surfaces seems to be a key technique for
      obtaining thick films instead of vertically aligned nanostructures as reported in
      many literatures. All the hydrothermal ZnO layers showed the large grains with
      hexagonal end facets and were highly oriented towards the c-axis direction.
      Photoluminescence (PL) spectra of the hydrothermal layers were composed of the
      ultraviolet (UV) emission (370 to 380 nm) and the visible emission (481 to 491
      nm), and the intensity ratio of the former emission (I UV) to the latter emission
      (I VIS) changed, depending on both the molarity of the solution and temperature.
      It is surprising that all the Hall mobilities for the hydrothermal ZnO layers
      were significantly larger than those for their corresponding CVD seed films. It
      was also found that, for the hydrothermal films grown at 70 degrees C to 90
      degrees C, the molarity dependences of I UV/I VIS resembled those of mobilities,
      implying that the mobility in the film is affected by the structural defects. The
      highest mobility of 166 cm(2)/Vs was achieved on the hydrothermal film with the
      carrier concentration of 1.65 * 10(17) cm(-3) grown from the aqueous solution of
      40 mM at 70 degrees C. 

PMID- 25852307
TI  - Effects of architectures and H2O2 additions on the photocatalytic performance of
      hierarchical Cu2O nanostructures.
AB  - Cu2O hierarchical nanostructures with different morphologies were successfully
      synthesized by a solvothermal method using copper (II) nitrate trihydrate
      (Cu(NO3)2?3H2O) and ethylene glycol (EG) as initial reagents. The obtained
      nanostructures were characterized by X-ray diffraction (XRD), scanning electron
      microscopy (SEM), Brunauer-Emmett-Teller (BET) specific surface area test, and UV
      vis spectroscopy. The synthesis conditions (copper source, temperature, and
      reaction time) dominated the compositions and the formation of crystals with
      different morphologies. The visible light photocatalytic properties of as
      prepared Cu2O nanostructures were investigated with and without hydrogen peroxide
      (H2O2), and the effect of H2O2 were evaluated by monitoring the degradation of
      methyl orange (MO) with various amounts of H2O2. It was revealed that the degree
      of the photodegradation of MO depends on the amount of H2O2 and the morphology of
      Cu2O. 

PMID- 25852308
TI  - Seed/catalyst-free growth of zinc oxide on graphene by thermal evaporation:
      effects of substrate inclination angles and graphene thicknesses.
AB  - A seed/catalyst-free growth of ZnO on graphene by thermal evaporation of Zn in
      the presence of O2 gas was further studied. The effects of substrate positions
      and graphene thicknesses on the morphological, structural, and optical properties
      were found to be very pronounced. By setting the substrate to be inclined at 90
      degrees , the growth of ZnO nanostructures, namely, nanoclusters and nanorods, on
      single-layer (SL) graphene was successfully realized at temperatures of 600
      degrees C and 800 degrees C, respectively. For the growth on multilayer (ML)
      graphene at 600 degrees C with an inclination angle of 90 degrees , the grown
      structures show extremely thick and continuous cluster structures as compared to
      the growth with substrate's inclination angle of 45 degrees . Moreover, the base
      of nanorod structures grown at 800 degrees C with an inclination angle of 90
      degrees  also become thicker as compared to 45 degrees , even though their
      densities and aspect ratios were almost unchanged. Photoluminescence (PL) spectra
      of the grown ZnO structures were composed of the UV emission (378-386 nm) and the
      visible emission (517-550 nm), and the intensity ratio of the former emission (I
      UV) to the latter emission (I VIS) changed, depending on the temperature. The
      structures grown at a low temperature of 600 degrees C show the highest value of
      I UV/I VIS of 16.2, which is almost two times higher than the structures grown on
      SL graphene, indicating fewer structural defects. The possible growth mechanism
      was proposed and described which considered both the nucleation and oxidation
      processes. From the results obtained, it can be concluded that temperature below
      800 degrees C, substrate position inclined at 90 degrees  towards the gas flow,
      and ML graphene seems to be preferable parameters for the growth of ZnO
      structures by thermal evaporation because these factors can be used to overcome
      the problem of graphene's oxidation that takes place during the growth. 

PMID- 25852309
TI  - Morphological engineering of self-assembled nanostructures at nanoscale on
      faceted GaAs nanowires by droplet epitaxy.
AB  - Fabrication of advanced artificial nanomaterials is a long-term pursuit to
      fulfill the promises of nanomaterials and it is of utter importance to manipulate
      materials at nanoscale to meet urgent demands of nanostructures with designed
      properties. Herein, we demonstrate the morphological tailoring of self-assembled
      nanostructures on faceted GaAs nanowires (NWs). The NWs are deposited on
      different kinds of substrates. Triangular and hexagonal prism morphologies are
      obtained, and their corresponding {110} sidewalls act as platforms for the
      nucleation of gallium droplets (GDs). We demonstrate that the morphologies of the
      nanostructures depend not only on the annealing conditions but also on the
      morphologies of the NWs' sidewalls. Here, we achieve morphological engineering in
      the form of novel quantum dots (QDs), 'square' quantum rings (QRs), 'rectangular'
      QRs, 3D QRs, crescent-shaped QRs, and nano-antidots. The evolution mechanisms for
      the peculiar morphologies of both NWs and nanostructures are modeled and
      discussed in detail. This work shows the potential of combining nano-structural
      engineering with NWs to achieve multifunctional properties and applications. 

PMID- 25852310
TI  - Gene expression profile of human lung epithelial cells chronically exposed to
      single-walled carbon nanotubes.
AB  - A rapid increase in utility of engineered nanomaterials, including carbon
      nanotubes (CNTs), has raised a concern over their safety. Based on recent
      evidence from animal studies, pulmonary exposure of CNTs may lead to nanoparticle
      accumulation in the deep lung without effective clearance which could interact
      with local lung cells for a long period of time. Physicochemical similarities of
      CNTs to asbestos fibers may contribute to their asbestos-like carcinogenic
      potential after long-term exposure, which has not been well addressed. More
      studies are needed to identify and predict the carcinogenic potential and
      mechanisms for promoting their safe use. Our previous study reported a long-term
      in vitro exposure model for CNT carcinogenicity and showed that 6-month sub
      chronic exposure of single-walled carbon nanotubes (SWCNT) causes malignant
      transformation of human lung epithelial cells. In addition, the transformed cells
      induced tumor formation in mice and exhibited an apoptosis resistant phenotype, a
      key characteristic of cancer cells. Although the potential role of p53 in the
      transformation process was identified, the underlying mechanisms of oncogenesis
      remain largely undefined. Here, we further examined the gene expression profile
      by using genome microarrays to profile molecular mechanisms of SWCNT oncogenesis.
      Based on differentially expressed genes, possible mechanisms of SWCNT-associated
      apoptosis resistance and oncogenesis were identified, which included activation
      of pAkt/p53/Bcl-2 signaling axis, increased gene expression of Ras family for
      cell cycle control, Dsh-mediated Notch 1, and downregulation of apoptotic genes
      BAX and Noxa. Activated immune responses were among the major changes of
      biological function. Our findings shed light on potential molecular mechanisms
      and signaling pathways involved in SWCNT oncogenic potential. 

PMID- 25852311
TI  - Unusual structural and electronic properties of porous silicene and germanene:
      insights from first-principles calculations.
AB  - Using first-principles calculations, we investigate the geometric structures and
      electronic properties of porous silicene and germanene nanosheets, which are the
      Si and Ge analogues of alpha-graphyne (referred to as silicyne and germanyne). It
      is found that the elemental silicyne and germanyne sheets are energetically
      unfavourable. However, after the C-substitution, the hybrid graphyne-like sheets
      (c-silicyne/c-germanyne) possess robust energetic and dynamical stabilities.
      Different from silicene and germanene, c-silicyne is a flat sheet, and c
      germanyne is buckled with a distinct half-hilled conformation. Such asymmetric
      buckling structure causes the semiconducting behaviour into c-germanyne. While in
      c-silicyne, the semimetallic Dirac-like property is kept at the nonmagnetic
      state, but a spontaneous antiferromagnetism produces the massive Dirac fermions
      and opens a sizeable gap between Dirac cones. A tensile strain can further
      enhance the antiferromagnetism, which also linearly modulates the gap value
      without altering the direct-bandgap feature. Through strain engineering, c
      silicyne can form a type-II band alignment with the MoS 2 sheet. The combined c
      silicyne/MoS 2 nanostructure has a high power conversion efficiency beyond 20%
      for photovoltaic solar cells, enabling a fascinating utilization in the fields of
      solar energy and nano-devices. 

PMID- 25852312
TI  - The enhanced anticoagulation for graphene induced by COOH(+) ion implantation.
AB  - Graphene may have attractive properties for some biomedical applications, but its
      potential adverse biological effects, in particular, possible modulation when it
      comes in contact with blood, require further investigation. Little is known about
      the influence of exposure to COOH(+)-implanted graphene (COOH(+)/graphene)
      interacting with red blood cells and platelets. In this paper, COOH(+)/graphene
      was prepared by modified Hummers' method and implanted by COOH(+) ions. The
      structure and surface chemical and physical properties of COOH(+)/graphene were
      characterized by scanning electron microscopy (SEM), X-ray photoelectron
      spectroscopy (XPS), and contact angle measurement. Systematic evaluation of
      anticoagulation, including in vitro platelet adhesion assays and hemolytic
      assays, proved that COOH(+)/graphene has significant anticoagulation. In
      addition, at the dose of 5 * 10(17) ions/cm(2), COOH(+)/graphene responded best
      on platelet adhesion, aggregation, and platelet activation. 

PMID- 25852313
TI  - Reduction of breakdown threshold by metal nanoparticle seeding in a DC
      microdischarge.
AB  - Significant reduction of the breakdown threshold in a DC microdischarge via
      seeding metal nanoparticles has been demonstrated. Compared to standard Paschen
      curves in dry air, reductions in the breakdown voltage of 5% to 25% were obtained
      for PD values (the product of pressure and electrode gap distance) ranging from
      20 to 40 Torr-cm by seeding aluminum and iron nanoparticles with mean sizes of 75
      nm and 80 nm, respectively. No secondary energy source was required to achieve
      this breakdown threshold reduction. From high-speed chemiluminescence imaging of
      the discharge evolution, breakdown was shown to be initiated at reduced voltages.
      Following breakdown, the increase in temperature ignited some of the
      nanoparticles near the cathode. Results suggest that possible charging of the
      nanoparticles within the gap may reduce the effective transient distance, leading
      to the threshold reduction. 

PMID- 25852314
TI  - NH3-treated WO3 as low-cost and efficient counter electrode for dye-sensitized
      solar cells.
AB  - A novel low-cost and efficient counter electrode (CE) was obtained by treating
      catalytic inert tungsten trioxide (WO3) nanomaterial in NH3 atmosphere at
      elevated temperatures. The formation of tungsten oxynitride from WO3 after NH3
      treatment, as evidenced by X-ray photoelectron spectroscopy and X-ray
      diffraction, increases the catalytic activity of the CE. Correspondingly, the
      power conversion efficiency (PCE) of the DSC is significantly increased from 0.9%
      for pristine WO3 CE to 5.9% for NH3-treated WO3 CE. The photovoltaic performance
      of DSC using NH3-treated WO3 CE is comparable to that of DSC using standard Pt CE
      (with a PCE of 6.0%). In addition, it is also shown that NH3 treatment is more
      efficient than H2 or N2 treatment in enhancing the catalytic performance of WO3
      CE. This work highlights the potential of NH3-treated WO3 for the application in
      DSCs and provides a facile method to get highly efficient and low-cost CEs from
      catalytic inert metal oxides. 

PMID- 25852315
TI  - Nanosphere-in-a-nanoegg: damping the high-order modes induced by symmetry
      breaking.
AB  - We study the optical properties of the nanosphere-in-a-nanoegg structure (NSNE)
      by the three-dimensional finite difference time domain method. We demonstrate the
      suppression of the high-order plasmon modes in NSNE, which is induced by the
      plasmon interaction between the inner nanosphere and the outer nanoegg shell. A
      two-layer plasmon hybridization model is presented to explain this mechanism. The
      results we showed for plasmon mode suppression would be important to the design
      of the metal plasmonic devices. In addition, due to high tunable plasmon
      resonances in the near-infrared region (700 to 1,300 nm) with sub-100-nm size,
      NSNE can serve as a good substitute for the Au-silica-Au multilayer nanoshells in
      biological applications. Furthermore, compared with the Au-silica-Au nanoshells,
      NSNE has the advantage that the strong field enhancement can be achieved at the
      outer surface of the Au shell. 

PMID- 25852316
TI  - Real-time detection of chlorine gas using Ni/Si shell/core nanowires.
AB  - We demonstrate the selective adsorption of Ni/Si shell/core nanowires (Ni-Si NWs)
      with a Ni outer shell and a Si inner core on molecularly patterned substrates and
      their application to sensors for the detection of chlorine gas, a toxic halogen
      gas. The molecularly patterned substrates consisted of polar SiO2 regions and
      nonpolar regions of self-assembled monolayers of octadecyltrichlorosilane (OTS).
      The NWs showed selective adsorption on the polar SiO2 regions, avoiding assembly
      on the nonpolar OTS regions. Utilizing these assembled Ni-Si NWs, we demonstrate
      a sensor for the detection of chlorine gas. The utilization of Ni-Si NWs resulted
      in a much larger sensor response of approximately 23% to 5 ppm of chlorine gas
      compared to bare Ni NWs, due to the increased surface-to-volume ratio of the Ni
      Si shell/core structure. We expect that our sensor will be utilized in the future
      for the real-time detection of halogen gases including chlorine with high
      sensitivity and fast response. 

PMID- 25852317
TI  - In situ growth of ZnO nanoparticles in precursor-insensitive water-in-oil
      microemulsion as soft nanoreactors.
AB  - Zinc oxide (ZnO) nanostructures of uniform shapes and sizes (spherical, needle
      like, and acicular) were directly synthesized using a relatively precursor
      insensitive water-in-n-heptane microemulsion system stabilized by a mixture of
      cationic and non-ionic surfactants. With this colloidal system, the synthesized
      ZnO possesses the highest reported surface area (76 m(2) g(-1)) among the
      published reports utilizing other microemulsion systems. Such precursor
      insensitivity allowed studying the effect of Zn precursor:precipitating agent
      molar ratio (as high as 1:8) on the particle size, specific surface area,
      porosity, and morphology of the synthesized nanoparticles. The interaction of the
      cationic surfactant head groups and their Br(-) counter ions with Zn(2+) and OH(
      ) ions is believed to play a major role in controlling the ZnO characteristics.
      Due to such interactions, it is believed that the nucleation processes are
      retarded while the growth is more dominating if compared with other microemulsion
      systems. 

PMID- 25852318
TI  - Effect of grain size on thermal transport in post-annealed antimony telluride
      thin films.
AB  - The effects of grain size and strain on the temperature-dependent thermal
      transport of antimony telluride (Sb2Te3) thin films, controlled using post
      annealing temperatures of 200 degrees C to 350 degrees C, were investigated using
      the 3-omega method. The measured total thermal conductivities of 400-nm-thick
      thin films annealed at temperatures of 200 degrees C, 250 degrees C, 300 degrees
      C, 320 degrees C, and 350 degrees C were determined to be 2.0 to 3.7 W/m . K in
      the 20 to 300 K temperature range. We found that the film grain size, rather than
      the strain, had the most prominent effect on the reduction of the total thermal
      conductivity. To confirm the effect of grain size on temperature-dependent
      thermal transport in the thin films, the experimental results were analyzed using
      a modified Callaway model approach. 

PMID- 25852319
TI  - Electrical transport properties of an isolated CdS microrope composed of twisted
      nanowires.
AB  - CdS is one of the important II-VI group semiconductors. In this paper, the
      electrical transport behavior of an individual CdS microrope composed of twisted
      nanowires is studied. It is found that the current-voltage (I-V) characteristics
      show two distinct power law regions from 360 down to 60 K. Space-charge-limited
      current (SCLC) theory is used to explain these temperature- and electric-field
      dependent I-V curves. The I-V data can be well fitted by this theory above 100 K,
      and the corresponding carrier mobility, trap energy, and trap concentration are
      also obtained. However, the I-V data exhibit some features of the Coulomb
      blockade effect below 80 K. 

PMID- 25852320
TI  - Axially connected nanowire core-shell p-n junctions: a composite structure for
      high-efficiency solar cells.
AB  - A composite nanostructure for high-efficiency solar cells that axially connects
      nanowire core-shell p-n junctions is proposed. By axially connecting the p-n
      junctions in one nanowire, the solar spectrum is separated and absorbed in the
      top and bottom cells with respect to the wavelength. The unique structure of
      nanowire p-n junctions enables substantial light absorption along the nanowire
      and efficient radial carrier separation and collection. A coupled three
      dimensional optoelectronic simulation is used to evaluate the performance of the
      structure. With an excellent current matching, a promising efficiency of 19.9%
      can be achieved at a low filling ratio of 0.283 (the density of the nanowire
      array), which is much higher than the tandem axial p-n junctions. 

PMID- 25852321
TI  - Mechanical properties of carbyne: experiment and simulations.
AB  - The results of the high-field technique for obtaining and testing the carbyne
      strength in situ are presented. By using molecular dynamics simulation and ab
      initio calculations, a comprehensive analysis of the results is executed. High
      field technique for experimental measurement of the carbyne strength in situ is
      briefly described. It is shown that the technique used gives a lower estimation
      for strength of carbyne, which equals 251 GPa at T = 77 K. This value is close to
      the strength 7.85 nN (250 GPa) of contact atomic bond between carbyne and
      graphene sheet, from which the monatomic chain is pulled. The strength of carbyne
      itself is determined by strength of an edge atomic bond and it is ~ 12.35 nN (393
      GPa) at T = 0 K. For carbynes containing more than 10 to 12 atoms, the
      coefficient of elasticity (k Y  = 145.40 nN) and the elastic modulus (Y = 4631
      GPa) are ascertain. 

PMID- 25852322
TI  - Inductive crystallization effect of atomic-layer-deposited Hf0.5Zr0.5O2 films for
      ferroelectric application.
AB  - Ferroelectric Hf x Zr1-x O2 thin films are considered promising candidates for
      future lead-free CMOS-compatible ferroelectric memory application. The inductive
      crystallization behaviors and the ferroelectric performance of Hf0.5Zr0.5O2 thin
      films prepared by atomic layer deposition were investigated. Inductive
      crystallization can be induced by the film growth condition and appropriate top
      electrode selection. In this work, a Ni/Hf0.5Zr0.5O2/Ru/Si stack annealed at 550
      degrees C for 30 s in N2 ambient after the Ni top electrode has been deposited
      was manufactured, and it shows the best ferroelectric hysteresis loop in the
      dielectric thickness of 25 nm, with a remanent polarization value of 6 MUC/cm(2)
      and a coercive field strength of 2.4 MV/cm measured at 10 kHz. Endurance,
      retention, and domain switching current characteristics were evaluated well for
      potential application in the field of ferroelectric field effect transistor
      (FeFET) and nonvolatile ferroelectric memories (FeRAM). 

PMID- 25852323
TI  - Investigation of monolithic passively mode-locked quantum dot lasers with
      extremely low repetition frequency.
AB  - The dynamical regimes and performance optimization of quantum dot monolithic
      passively mode-locked lasers with extremely low repetition rate are investigated
      using the numerical method. A modified multisection delayed differential equation
      model is proposed to accomplish simulations of both two-section and three-section
      passively mode-locked lasers with long cavity. According to the numerical
      simulations, it is shown that fundamental and harmonic mode-locking regimes can
      be multistable over a wide current range. These dynamic regimes are studied, and
      the reasons for their existence are explained. In addition, we demonstrate that
      fundamental pulses with higher peak power can be achieved when the laser is
      designed to work in a region with smaller differential gain. 

PMID- 25852324
TI  - Studies on the mechanical stretchability of transparent conductive film based on
      graphene-metal nanowire structures.
AB  - Transparent electrodes with superior flexibility and stretchability as well as
      good electrical and optical properties are required for applications in wearable
      electronics with comfort designs and high performances. Here, we present hybrid
      nanostructures as stretchable and transparent electrodes based on graphene and
      networks of metal nanowires, and investigate their optical, electrical, and
      mechanical properties. High electrical and optical characteristics, superb
      bendability (folded in half), excellent stretchability (10,000 times in
      stretching cycles with 100% in tensile strain toward a uniaxial direction and 30%
      in tensile strain toward a multi-axial direction), strong robustness against
      electrical breakdown and thermal oxidation were obtained through comprehensive
      study. We believe that these results suggest a substantial promise application in
      future electronics. 

PMID- 25852325
TI  - Human-like collagen protein-coated magnetic nanoparticles with high magnetic
      hyperthermia performance and improved biocompatibility.
AB  - Human-like collagen (HLC)-coated monodispersed superparamagnetic Fe3O4
      nanoparticles have been successfully prepared to investigate its effect on heat
      induction property and cell toxicity. After coating of HLC, the sample shows a
      faster rate of temperature increase under an alternating magnetic field although
      it has a reduced saturation magnetization. This is most probably a result of the
      effective heat conduction and good colloid stability due to the high charge of
      HLC on the surface. In addition, compared with Fe3O4 nanoparticles before coating
      with HLC, HLC-coated Fe3O4 nanoparticles do not induce notable cytotoxic effect
      at higher concentration which indicates that HLC-coated Fe3O4 nanoparticles has
      improved biocompatibility. Our results clearly show that Fe3O4 nanoparticles
      after coating with HLC not only possess effective heat induction for cancer
      treatment but also have improved biocompatibility for biomedicine applications. 

PMID- 25852326
TI  - Enhanced efficiency of inverted polymer solar cells by using solution-processed
      TiOx/CsOx cathode buffer layer.
AB  - In this work, a double-buffer film of TiOx coated with CsOx (TiOx/CsOx) was
      solution prepared to be applied in poly(3-hexylthiophene):indene-C60 bisadduct
      (P3HT:ICBA) and P3HT:[6,6]-phenyl-C61-butyric acid methyl ester (PCBM) inverted
      polymer solar cells (PSCs). Compared with TiOx films and CsOx films, the
      TiOx/CsOx double-buffer film exhibited a favorable energy-level alignment among
      TiOx, CsOx, and the electron acceptor of PCBM or ICBA a better surface
      morphology; and an enhanced wetting and adhesion property with a contact angle of
      21.0 degrees , leading to a higher electron mobility of 5.52 * 10(-3) cm(2) V(
      1).s(-1). Moreover, the P3HT:ICBA and P3HT:PCBM photovoltaic devices with the
      double-buffer film showed the best power conversion efficiency up to 5.65% and
      3.76%, respectively. Our results not only present that the double-buffer film is
      superior than the single film of TiOx and CsOx, but also imply that the solution
      processed film has a potential to be generally used in roll-to-roll processed
      organic photovoltaic devices. 

PMID- 25852327
TI  - Microstructure, optical properties, and catalytic performance of Cu2O-modified
      ZnO nanorods prepared by electrodeposition.
AB  - Cu2O-modified ZnO nanorods are prepared by a two-step electrodeposition method on
      ITO substrates, and the deposition time of Cu2O is 0, 1, 5, and 10 min,
      respectively. Cu2O particles are embedded in the interspaces of the ZnO nanorods,
      and the amounts of the Cu2O particles increase obviously when the deposition time
      lasts longer. The peaks corresponding to ZnO nanorods and Cu2O particles are
      detected from scanning electron microscope (SEM) and X-ray diffraction (XRD)
      results. UV-vis absorption spectra measurements have shown the bandgaps of ZnO
      nanorods shift from 3.22 to 2.75 eV. The methyl orange (MO) concentration can be
      reduced to around 15% in 100 min with Cu2O electrodeposition time for 10 min. 

PMID- 25852328
TI  - Strong localization effect and carrier relaxation dynamics in self-assembled
      InGaN quantum dots emitting in the green.
AB  - Strong localization effect in self-assembled InGaN quantum dots (QDs) grown by
      metalorganic chemical vapor deposition has been evidenced by temperature
      dependent photoluminescence (PL) at different excitation power. The integrated
      emission intensity increases gradually in the range from 30 to 160 K and then
      decreases with a further increase in temperature at high excitation intensity,
      while this phenomenon disappeared at low excitation intensity. Under high
      excitation, about 40% emission enhancement at 160 K compared to that at low
      temperature, as well as a higher internal quantum efficiency (IQE) of 41.1%, was
      observed. A strong localization model is proposed to describe the possible
      processes of carrier transport, relaxation, and recombination. Using this model,
      the evolution of excitation-power-dependent emission intensity, shift of peak
      energy, and linewidth variation with elevating temperature is well explained.
      Finally, two-component decays of time-resolved PL (TRPL) with various excitation
      intensities are observed and analyzed with the biexponential model, which enables
      us to further understand the carrier relaxation dynamics in the InGaN QDs. 

PMID- 25852329
TI  - Optical properties and bandgap evolution of ALD HfSiOx films.
AB  - Hafnium silicate films with pure HfO2 and SiO2 samples as references were
      fabricated by atomic layer deposition (ALD) in this work. The optical properties
      of the films as a function of the film composition were measured by vacuum
      ultraviolet (VUV) ellipsometer in the energy range of 0.6 to 8.5 eV, and they
      were investigated systematically based on the Gaussian dispersion model.
      Experimental results show that optical constants and bandgap of the hafnium
      silicate films can be tuned by the film composition, and a nonlinear change
      behavior of bandgap with SiO2 fraction was observed. This phenomenon mainly
      originates from the intermixture of d-state electrons in HfO2 and Si-O
      antibonding states in SiO2. 

PMID- 25852330
TI  - Influence of the local structure in phase-change materials on their dielectric
      permittivity.
AB  - Ge-Sb-Te alloys, which belong to the phase-change materials, are promising
      materials for data storage and display and data visualization applications due to
      their unique properties. This includes a remarkable difference of their
      electrical and optical properties in the amorphous and crystalline state.
      Pronounced change of optical properties for Ge-Sb-Te alloys is linked to the
      different bonding types and different atomic arrangements in amorphous and
      crystalline states. The dielectric function of phase-change materials has been
      investigated in the far infrared (FIR) range. Phonons have been detected by FTIR
      spectroscopy. Difference of the dispersion of the dielectric permittivity of
      amorphous and crystalline samples is caused by different structures in different
      states which contribute to the dielectric permittivity. 

PMID- 25852331
TI  - Preparation of silver colloids with improved uniformity and stable surface
      enhanced Raman scattering.
AB  - Silver colloids of uniform shape and size are prepared by a two-step reduction.
      Small silver particles form initially by the rapid reduction of silver nitrate
      with sodium citrate at 100 degrees C and then grow at 92 degrees C. The reaction
      processes and resulting silver colloids are characterized by transmission
      electron microscopy, ultraviolet-visible absorption spectrophotometry, zeta
      potential measurements, and Ag(+) concentration analysis. The surface-enhanced
      Raman scattering (SERS) activity of the silver colloids is then investigated,
      using crystal violet (CV) as a SERS probe. The silver colloids exhibit uniform
      shape and size and stable SERS activity. The average size of the silver particles
      is 47 nm (14% relative standard deviation), while the average sizes of the silver
      colloids prepared at 100 degrees C and 92 degrees C are 41 (30%) and 71 nm (33%),
      respectively. 

PMID- 25852333
TI  - Fe-Al-C carbide phase nano-layer investigation as a substrate for epitaxial
      diamond growth.
AB  - Calculations of electron structure of supercells consisting of several layers of
      ordinary stoichiometric K-phase and modified K-phase, on which according to our
      assumptions epitaxial growth of diamonds is possible, were conducted. Stability
      of calculated cells was considered, and optimal number of layers of the
      stoichiometric K-phase in the supercell was determined in order for it to be
      thermodynamically stable. Electronic structure of carbon in the modified K-phase
      layer was considered and compared to electron structure of carbon in diamond. 

PMID- 25852332
TI  - Multidimensional effects of biologically synthesized silver nanoparticles in
      Helicobacter pylori, Helicobacter felis, and human lung (L132) and lung carcinoma
      A549 cells.
AB  - Silver nanoparticles (AgNPs) are prominent group of nanomaterials and are
      recognized for their diverse applications in various health sectors. This study
      aimed to synthesize the AgNPs using the leaf extract of Artemisia princeps as a
      bio-reductant. Furthermore, we evaluated the multidimensional effect of the
      biologically synthesized AgNPs in Helicobacter pylori, Helicobacter felis, and
      human lung (L132) and lung carcinoma (A549) cells. UV-visible (UV-vis)
      spectroscopy confirmed the synthesis of AgNPs. X-ray diffraction (XRD) indicated
      that the AgNPs are specifically indexed to a crystal structure. The results from
      Fourier transform infrared spectroscopy (FTIR) indicate that biomolecules are
      involved in the synthesis and stabilization of AgNPs. Dynamic light scattering
      (DLS) studies showed the average size distribution of the particle between 10 and
      40 nm, and transmission electron microscopy (TEM) confirmed that the AgNPs were
      significantly well separated and spherical with an average size of 20 nm. AgNPs
      caused dose-dependent decrease in cell viability and biofilm formation and
      increase in reactive oxygen species (ROS) generation and DNA fragmentation in H.
      pylori and H. felis. Furthermore, AgNPs induced mitochondrial-mediated apoptosis
      in A549 cells; conversely, AgNPs had no significant effects on L132 cells. The
      results from this study suggest that AgNPs could cause cell-specific apoptosis in
      mammalian cells. Our findings demonstrate that this environmentally friendly
      method for the synthesis of AgNPs and that the prepared AgNPs have
      multidimensional effects such as anti-bacterial and anti-biofilm activity against
      H. pylori and H. felis and also cytotoxic effects against human cancer cells.
      This report describes comprehensively the effects of AgNPs on bacteria and
      mammalian cells. We believe that biologically synthesized AgNPs will open a new
      avenue towards various biotechnological and biomedical applications in the near
      future. 

PMID- 25852334
TI  - Synthesis and detection the oxidization of Co cores of Co@SiO2 core-shell
      nanoparticles by in situ XRD and EXAFS.
AB  - In this paper, the Co@SiO2 core-shell nanoparticles were prepared by the sol-gel
      method. The oxidization of Co core nanoparticles was studied by the synchrotron
      radiation-based techniques including in situ X-ray diffraction (XRD) and X-ray
      absorption fine structure (XAFS) up to 800 degrees C in air and N2 protection
      conditions, respectively. It was found that the oxidization of Co cores is
      undergoing three steps regardless of being in air or in N2 protection condition.
      In the first step ranging from room temperature to 200 degrees C, the Co cores
      were dominated by Co(0) state as well as small amount of Co(2+) ions. When
      temperature was above 300 degrees C, the interface between Co cores and SiO2
      shells was gradually oxidized into Co(2+), and the CoO layer was observed. As the
      temperature increasing to 800 degrees C, the Co cores were oxidized to Co3O4 or
      Co3O4/CoO. Nevertheless, the oxidization kinetics of Co cores is different for
      the Co@SiO2 in air and N2 gas conditions. Generally, the O2 in the air could get
      through the SiO2 shells easily onto the Co core surface and induce the
      oxidization of the Co cores due to the mesoporous nature of the SiO2 shells.
      However, in N2 gas condition, the O atoms can only be from the SiO2 shells, so
      the diffusion effect of O atoms in the interface between Co core and SiO2 shell
      plays a key role. 

PMID- 25852335
TI  - Hot plasmonic electrons for generation of enhanced photocurrent in gold-TiO2
      nanocomposites.
AB  - In this manuscript, for the first time, we report a combination of
      electrophoretic and sintering approaches for introducing gold nanoparticles into
      nanoporous TiO2 films to generate 'hot' electrons resulting in a strong
      enhancement of photocurrent. The Au-TiO2 nanocomposite material was prepared by
      the electrophoretic deposition of gold nanoparticles into a porous
      nanoparticulate titanium dioxide film, creating a photoactive electrode. The
      composite film demonstrates a significant increase in the short circuit current
      (I sc) compared to unmodified TiO2 when excited at or close to the plasmon
      resonance of the gold nanoparticles. Then, we employed a thermal ripening process
      as a method of increasing the I sc of these electrodes and also as a method of
      tuning the plasmon peak position, with a high degree of selectivity. Photo
      electrochemical investigations revealed that the increase in photocurrent is
      attributed to the generation and separation of plasmonically generated hot
      electrons at the gold/TiO2 interface and also the inter-band generation of holes
      in gold nanoparticles by photons with lambda < 520 nm. Theoretical modelling
      outputs perfectly match our results obtained from photo-physical studies of the
      processes leading to enhanced photocurrent. 

PMID- 25852336
TI  - Impact of program/erase operation on the performances of oxide-based resistive
      switching memory.
AB  - Further performance improvement is necessary for resistive random access memory
      (RRAM) to realize its commercialization. In this work, a novel pulse operation
      method is proposed to improve the performance of RRAM based on Ti/HfO2/Pt
      structure. In the DC voltage sweep of the RRAM device, the SET transition is
      abrupt under positive bias. If current sweep with positive bias is utilized in
      SET process, the SET switching will become gradual, so SET is current controlled.
      In the negative voltage sweep for RESET process, the change of current with
      applied voltage is gradual, so RESET is voltage controlled. Current sweep SET and
      voltage sweep RESET shows better controllability on the parameter variation.
      Considering the SET/RESET characteristics in DC sweep, in the corresponding pulse
      operation, the width and height of the pulse series can be adjusted to control
      the SET and RESET process, respectively. Our new method is different from the
      traditional pulse operation in which both the width and height of program/erase
      pulse are simply kept constant which would lead to unnecessary damage to the
      device. In our new method, in each program or erase operation, a series of pulses
      with the width/height gradually increased are made use of to fully finish the
      SET/RESET switching but no excessive stress is generated at the same time, so
      width/height-controlled accurate SET/RESET can be achieved. Through the
      operation, the uniformity and endurance of the RRAM device has been significantly
      improved. 

PMID- 25852337
TI  - Performance evaluation of multi-junction solar cells by spatially resolved
      electroluminescence microscopy.
AB  - An electroluminescence microscopy combined with a spectroscopy was developed to
      visually analyze multi-junction solar cells. Triple-junction solar cells with
      different conversion efficiencies were characterized by using this system. The
      results showed that the mechanical damages and material defects in solar cells
      can be clearly distinguished, indicating a high-resolution imaging. The external
      quantum efficiency (EQE) measurements demonstrated that different types of
      defects or damages impacted cell performance in various degrees and the electric
      leakage mostly degraded the EQE. Meanwhile, we analyzed the relationship between
      electroluminescence intensity and short-circuit current density J SC. The results
      indicated that the gray value of the electroluminescence image corresponding to
      the intensity was almost proportional to J SC. This technology provides a
      potential way to evaluate the current matching status of multi-junction solar
      cells. 

PMID- 25852338
TI  - Morphology and electronic structure of nanoscale powders of calcium
      hydroxyapatite.
AB  - Atomic force microscopy, infrared spectroscopy and NMR studied morphological and
      physicochemical properties of calcium hydroxyapatite powders produced by changing
      the temperature parameters of synthesis. Features of morphology formation of
      calcium hydroxyapatite nanoparticles with an annealing temperature within 200
      degrees C to 1,100 degrees C were determined. It is shown that the particle size
      of the apatite obtained that annealed 700 degrees C is 40 nm corresponding to the
      particle size of apatite in native bone. The effect of dimension factor on
      structural parameters of calcium hydroxyapatite is manifested in a more local
      symmetry of the PO4 (3-) tetrahedra at nanodispersed calcium hydroxyapatite. 

PMID- 25852339
TI  - Synthesis of copper micro-rods with layered nano-structure by thermal
      decomposition of the coordination complex Cu(BTA)2.
AB  - Porous metallic copper was successfully prepared by a simple thermal
      decomposition strategy. A coordination compound of Cu(BTA)2 with the morphology
      of micro-rod crystal was synthesized as the precursor. The precursor to copper
      transformation was performed and annealed at 600 degrees C with the shape
      preserved. The copper micro-rods are assembled from unique thin lamellar layers,
      each with the thickness of approximately 200 nm and nano-pores of approximately
      20 to 100 nm. This morphology is highly related to the crystal structure of the
      precursor. The mechanism of the morphology formation is proposed, which would be
      able to offer a guideline toward porous metals with controllable macro/micro/nano
      structures by the precursor crystal growth and design. 

PMID- 25852340
TI  - Folic-acid-conjugated pullulan/poly(DL-lactide-co-glycolide) graft copolymer
      nanoparticles for folate-receptor-mediated drug delivery.
AB  - BACKGROUND: Nanoparticles have been extensively investigated for targeted
      delivery of anticancer drugs. Since the folate receptor is universally over
      expressed on the tumor cell membrane, folic acid is often used to modify the fate
      of nanoparticles in biologicals. METHODS: To fabricate targetable nanoparticles,
      folic acid was conjugated to a pullulan backbone and poly(DL-lactide-co
      glycolide) (PLGA) (abbreviated as FAPuLG) was conjugated. KB cells and NIH3T3
      cell-bearing mice were prepared to prove folate receptor targeting of FAPuLG
      nanoparticles. RESULTS AND DISCUSSION: Nanoparticles of FAPuLG copolymer that
      self-assembled in water were small with diameters <200 nm. Doxorubicin (DOX) as a
      model drug was incorporated into the FAPuLG nanoparticles that were used to treat
      folate receptor over-expressing KB human carcinoma cells. Fluorescence microscopy
      revealed that DOX-incorporated FAPuLG nanoparticles induced strong red
      fluorescence in the KB cells in the absence of folic acid. However, fluorescence
      intensity was decreased by blocking folate receptors. Antitumor activity of
      FAPuLG nanoparticles against KB cells in vitro was also decreased by blocking
      folate receptors. In animal study using near-infrared dye-conjugated FAPuLG
      nanoparticles, fluorescence intensity was significantly higher at KB solid tumor
      than that of NIH3T3. CONCLUSIONS: The results indicate that FAPuLG nanoparticles
      can target the folate receptor of tumor cells. FAPuLG nanoparticles are a
      promising candidate for active targeting of anticancer agents.

PMID- 25852341
TI  - Atomic layer deposition for fabrication of HfO2/Al2O3 thin films with high laser
      induced damage thresholds.
AB  - Previous research on the laser damage resistance of thin films deposited by
      atomic layer deposition (ALD) is rare. In this work, the ALD process for thin
      film generation was investigated using different process parameters such as
      various precursor types and pulse duration. The laser-induced damage threshold
      (LIDT) was measured as a key property for thin films used as laser system
      components. Reasons for film damaged were also investigated. The LIDTs for thin
      films deposited by improved process parameters reached a higher level than
      previously measured. Specifically, the LIDT of the Al2O3 thin film reached 40
      J/cm(2). The LIDT of the HfO2/Al2O3 anti-reflector film reached 18 J/cm(2), the
      highest value reported for ALD single and anti-reflect films. In addition, it was
      shown that the LIDT could be improved by further altering the process parameters.
      All results show that ALD is an effective film deposition technique for
      fabrication of thin film components for high-power laser systems. 

PMID- 25852342
TI  - Polarized Raman spectroscopy with differing angles of laser incidence on single
      layer graphene.
AB  - Chemical vapor deposition (CVD)-grown single-layer graphene samples, transferred
      onto a transmission electron microscope (TEM) grid and onto a quartz plate, were
      studied using polarized Raman spectroscopy with differing angles of laser
      incidence (theta). Two different polarization configurations are used. In an in
      plane configuration, the polarization direction of both incident and scattered
      light is parallel to the graphene plane. In an out-of-plane configuration, the
      angle between the polarization vector and the graphene plane is the same as the
      angle of laser incidence (theta). The normalized Raman intensity of the G-band
      measured in the out-of-plane configuration, with respect to that in the in-plane
      configuration, was analyzed as a function of theta. The normalized Raman
      intensity showed approximately cos(2) theta-dependence up to theta = 70 degrees ,
      which can be explained by the fact that only the electric field component of the
      incident and the scattered photon in the out-of-plane configuration projected
      onto the graphene plane can contribute to the Raman scattering process because of
      the perfect confinement of the electrons to the graphene plane. 

PMID- 25852343
TI  - The impact of thickness and thermal annealing on refractive index for aluminum
      oxide thin films deposited by atomic layer deposition.
AB  - The aluminum oxide (Al2O3) thin films with various thicknesses under 50 nm were
      deposited by atomic layer deposition (ALD) on silicon substrate. The surface
      topography investigated by atomic force microscopy (AFM) revealed that the
      samples were smooth and crack-free. The ellipsometric spectra of Al2O3 thin films
      were measured and analyzed before and after annealing in nitrogen condition in
      the wavelength range from 250 to 1,000 nm, respectively. The refractive index of
      Al2O3 thin films was described by Cauchy model and the ellipsometric spectra data
      were fitted to a five-medium model consisting of Si substrate/SiO2 layer/Al2O3
      layer/surface roughness/air ambient structure. It is found that the refractive
      index of Al2O3 thin films decrease with increasing film thickness and the
      changing trend revised after annealing. The phenomenon is believed to arise from
      the mechanical stress in ALD-Al2O3 thin films. A thickness transition is also
      found by transmission electron microscopy (TEM) and SE after 900 degrees C
      annealing. 

PMID- 25852344
TI  - Magnetic and electric properties of stoichiometric BiMnO3 thin films.
AB  - It has been suggested that BiMnO3 is a material exhibiting both ferromagnetism
      and ferroelectricity. Stoichiometry is rather easily achieved in a
      polycrystalline sample, and ferromagnetic properties have been well documented
      for bulk samples. Stoichiometry in thin films has been difficult to obtain, and
      many physical properties have exhibit wide distributions mainly due to the
      stoichiometry problem. Thin film studies on BiMnO3 have not shown clear evidence
      of ferroelectricity, while other physical properties measured for the BiMnO3
      films showed wide spectra, which has been attributed to cation and/or oxygen
      vacancies. We fabricated BiMnO3 thin films with good stoichiometry and with
      ferromagnetic properties comparable to those reported for stoichiometric BiMnO3:
      Tc ~ 105 K and M sat ~ 3.6 MUB/Mn. The charge-electric field (Q-E) curve measured
      at 5 K was fairly linear and free from hysteresis and showed no ferroelectric
      order. This finding is consistent with the centrosymmetric crystal structure
      recently suggested by theoretical calculations and structural studies on ceramic
      samples of stoichiometric BiMnO3. 

PMID- 25852345
TI  - Quality and high yield synthesis of Ag nanowires by microwave-assisted
      hydrothermal method.
AB  - Silver nanowires (Ag-NWs) were obtained using microwave-assisted hydrothermal
      method (MAH). The main advantage of the method is its high NWs production which
      is greater than 90%. It is also easy, fast, and highly reproducible process. One
      of the drawbacks presented so far in the synthesis of nanostructures by polyol
      path is the high temperature used in the process, which is superior than the
      boiling point of solvent (ethylene glycol), and also its excessive reaction time.
      Here, Ag-NWs with diameters of 70 to 110 nm were synthesized in 5 min in large
      quantities. Results showed that dimensions and shape of nanowires were very
      susceptible to changes with reaction parameters. The reactor power and reactor
      fill capacity were important for the synthesis. It was found that the reaction
      time needs to be decreased because of the NWs which start to deform and break up
      due to significant increase in the pressure's system. Energy-dispersive X-ray
      spectroscopy and electron diffraction analysis (SAED) did not show corresponding
      phases of AgO. Some aspects about synthesis parameters which are related to the
      percent yield and size of nanowires are also discussed. 

PMID- 25852346
TI  - 'Cold' crystallization in nanostructurized 80GeSe2-20Ga2Se3 glass.
AB  - 'Cold' crystallization in 80GeSe2-20Ga2Se3 chalcogenide glass nanostructurized
      due to thermal annealing at 380 degrees C for 10, 25, 50, 80, and 100 h are
      probed with X-ray diffraction, atomic force, and scanning electron microscopy, as
      well as positron annihilation spectroscopy performed in positron annihilation
      lifetime and Doppler broadening of annihilation line modes. It is shown that
      changes in defect-related component in the fit of experimental positron lifetime
      spectra for nanocrystallized glasses testify in favor of structural fragmentation
      of larger free-volume entities into smaller ones. Nanocrystallites of Ga2Se3
      and/or GeGa4Se8 phases and prevalent GeSe2 phase extracted mainly at the surface
      of thermally treated samples with preceding nucleation and void agglomeration in
      the initial stage of annealing are characteristic features of cold
      crystallization. 

PMID- 25852347
TI  - Single-crystalline chromium silicide nanowires and their physical properties.
AB  - In this work, chromium disilicide nanowires were synthesized by chemical vapor
      deposition (CVD) processes on Si (100) substrates with hydrous chromium chloride
      (CrCl3 . 6H2O) as precursors. Processing parameters, including the temperature of
      Si (100) substrates and precursors, the gas flow rate, the heating time, and the
      different flow gas of reactions were varied and studied; additionally, the
      physical properties of the chromium disilicide nanowires were measured. It was
      found that single-crystal CrSi2 nanowires with a unique morphology were grown at
      700 degrees C, while single-crystal Cr5Si3 nanowires were grown at 750 degrees C
      in reducing gas atmosphere. The crystal structure and growth direction were
      identified, and the growth mechanism was proposed as well. This study with
      magnetism, photoluminescence, and field emission measurements demonstrates that
      CrSi2 nanowires are attractive choices for future applications in magnetic
      storage, photovoltaic, and field emitters. 

PMID- 25852348
TI  - High-resolution X-ray diffraction analysis of strain distribution in GaN
      nanowires on Si(111) substrate.
AB  - In this work, the influence of micro- and macro-deformation profiles in GaN
      nanowires (NWs) on the angular intensity distribution of X-ray diffraction are
      studied theoretically. The calculations are performed by using kinematical theory
      of X-ray diffraction and assuming the deformation decays exponentially from the
      NW/substrate interface. Theoretical modeling of X-ray scattering from NWs with
      different deformation profiles are carried out. We show that the shape of the
      (002) 2theta/omega X-ray diffraction profile (XDP) is defined by initial
      deformation at the NW's bottom and its relaxation depth given by the decay depth
      of the exponential deformation profile. Also, we demonstrate that macro
      deformation leads to XDP shift, whereas micro-deformations are the cause of XDP's
      asymmetry and its symmetrical broadening. A good correlation between calculated
      and experimental XDP from self-assembled GaN NWs on Si(111) substrate was
      achieved by taking into account all parameters of micro- and macro-deformation
      profiles. 

PMID- 25852349
TI  - Vanadia supported on nickel manganese oxide nanocatalysts for the catalytic
      oxidation of aromatic alcohols.
AB  - Vanadia nanoparticles supported on nickel manganese mixed oxides were synthesized
      by co-precipitation method. The catalytic properties of these materials were
      investigated for the oxidation of benzyl alcohol using molecular oxygen as
      oxidant. It was observed that the calcination temperature and the size of
      particles play an important role in the catalytic process. The catalyst was
      evaluated for its oxidation property against aliphatic and aromatic alcohols,
      which was found to display selectivity towards aromatic alcohols. The samples
      were characterized by employing scanning electron microscopy, transmission
      electron microscopy, X-ray diffraction, Brunauer-Emmett-Teller analysis,
      thermogravimetric analysis, and X-ray photoelectron spectroscopy. 

PMID- 25852350
TI  - Metal phthalocyanine: fullerene composite nanotubes via templating method for
      enhanced properties.
AB  - The use of templating method to synthesize the vanadyl 2,9,16,23-tetraphenoxy
      29H,31H-phthalocyanine (VOPcPhO):[6,6]-phenyl C71 butyric acid methyl ester
      (PC71BM) composite nanotubes is presented here. VOPcPhO is a p-type material and
      PC71BM is an n-type material which acts as an electron donor and electron
      acceptor, respectively. Both materials have been studied due to their potential
      applications as solar energy converter and organic electronics. High-resolution
      transmission electron microscope (HRTEM) and field emission scanning electron
      microscope (FESEM) images have shown the replication of the porous template
      diameter of approximately 200 nm with a superior incorporation of both VOPcPhO
      and PC71BM. VOPcPhO:PC71BM composite nanotubes showed the significant properties
      improvement if compared over their bulk heterojunction counterpart. UV-vis
      spectra of composite nanotubes show a shift to a longer wavelength at the
      absorption peaks. Significant quenching has been attained by the
      photoluminescence spectra of VOPcPhO:PC71BM composite nanotubes which supports
      the redshift of UV-vis absorption spectra. Presumably, the photo-induced charge
      transfer and charge carrier dissociation can be enhanced from the VOPcPhO:PC71BM
      composite nanotubes rather than the bulk heterojunction. 

PMID- 25852351
TI  - Enhanced photoelectrochemical and photocatalytic activity of WO3-surface modified
      TiO2 thin film.
AB  - Development of nanostructured photocatalysts for harnessing solar energy in
      energy-efficient and environmentally benign way remains an important area of
      research. Pure and WO3-surface modified thin films of TiO2 were prepared by
      magnetron sputtering on indium tin oxide glass, and photoelectrochemical and
      photocatalytic activities of these films were studied. TiO2 particles were <50
      nm, while deposited WO3 particles were <20 nm in size. An enhancement in the
      photocurrent was observed when the TiO2 surface was modified WO3 nanoparticles.
      Effect of potential, WO3 amount, and radiations of different wavelengths on the
      photoelectrochemical activity of TiO2 electrodes was investigated. Photocatalytic
      activity of TiO2 and WO3-modified TiO2 for the decolorization of methyl orange
      was tested. Graphical abstractWO3-surface modified TiO2 film showing better
      photocatalytic and photoelectrocatalytic activity. 

PMID- 25852352
TI  - Controllable size-selective method to prepare graphene quantum dots from graphene
      oxide.
AB  - We demonstrated one-step method to fabricate two different sizes of graphene
      quantum dots (GQDs) through chemical cutting from graphene oxide (GO), which had
      many advantages in terms of simple process, low cost, and large scale in
      manufacturing with higher production yield comparing to the reported methods.
      Several analytical methods were employed to characterize the composition and
      morphology of the resultants. Bright blue luminescent GQDs were obtained with a
      produced yield as high as 34.8%. Moreover, how the different sizes affect
      fluorescence wavelength mechanism was investigated in details. 

PMID- 25852353
TI  - Surface properties and biocompatibility of nanostructured TiO2 film deposited by
      RF magnetron sputtering.
AB  - Nanostructured TiO2 films are deposited on a silicon substrate using 150-W power
      from the RF magnetron sputtering at working pressures of 3 to 5 Pa, with no
      substrate bias, and at 3 Pa with a substrate bias of -50 V. X-ray diffraction
      (XRD) analysis reveals that TiO2 films deposited on unbiased as well as biased
      substrates are all amorphous. Surface properties such as surface roughness and
      wettability of TiO2 films, grown in a plasma environment, under biased and
      unbiased substrate conditions are reported according to the said parameters of RF
      power and the working pressures. Primary rat osteoblasts (MC3T3-E1) cells have
      been cultured on nanostructured TiO2 films fabricated at different conditions of
      substrate bias and working pressures. The effects of roughness and hydrophilicity
      of nanostructured TiO2 films on cell density and cell spreading have been
      discussed. 

PMID- 25852355
TI  - Lithium ionic conduction and relaxation dynamics of spark plasma sintered
      Li5La3Ta2O12 garnet nanoceramics.
AB  - In the present work, nanoceramics of Li5La3Ta2O12 (LLT) lithium ion conductors
      with the garnet-like structure are fabricated by spark plasma sintering (SPS)
      technique at different temperatures of 850 degrees C, 875 degrees C, and 900
      degrees C (SPS-850, SPS-875, and SPS-900). The grain size of the SPS nanoceramics
      is in the 50 to 100 nm range, indicating minimal grain growth during the SPS
      experiments. The ionic conduction and relaxation properties of the current
      garnets are studied by impedance spectroscopy (IS) measurements. The SPS-875
      garnets exhibit the highest total Li ionic conductivity of 1.25 * 10(-6) S/cm at
      RT, which is in the same range as the LLT garnets prepared by conventional
      sintering technique. The high conductivity of SPS-875 sample is due to the
      enhanced mobility of Li ions by one order of magnitude compared to SPS-850 and
      SPS-900 ceramics. The concentration of mobile Li(+) ions, n c, and their mobility
      are estimated from the analysis of the conductivity spectra at different
      temperatures. n c is found to be independent of temperature for the SPS
      nanoceramics, which implies that the conduction process is controlled by the
      Li(+) mobility. Interestingly, we found that only a small fraction of lithium
      ions of 3.9% out of the total lithium content are mobile and contribute to the
      conduction process. Moreover, the relaxation dynamics in the investigated
      materials have been studied through the electric modulus formalism. 

PMID- 25852354
TI  - Chances and limitations of nanosized titanium dioxide practical application in
      view of its physicochemical properties.
AB  - Nanotechnology is a field of science that is nowadays developing in a dynamic
      way. It seems to offer almost endless opportunities of contribution to many areas
      of economy and human activity, in general. Thanks to nanotechnology, the so
      called nanomaterials can be designed. They present structurally altered
      materials, with their physical, chemical and biological properties entirely
      differing from properties of the same materials manufactured in microtechnology.
      Nanotechnology creates a unique opportunity to modify the matter at the level of
      atoms and particles. Therefore, it has become possible to obtain items displaying
      new, useful properties, i.e. self-disinfecting and self-cleaning surfaces. Those
      surfaces are usually covered by a thin layer of a photocatalyst. The role of the
      photocatalyst is most of the time performed by the nanosized titanium dioxide
      (nano-TiO2). Excitation of nano-TiO2 by ultraviolet radiation initiates advanced
      oxidation processes and reactions leading to the creation of oxygen vacancies
      that bind water particles. As a result, photocatalytic surfaces are given new
      properties. Those properties can then be applied in a variety of disciplines,
      such as medicine, food hygiene, environmental protection or building industry.
      Practically, the applications include inactivation of microorganisms, degradation
      of toxins, removing pollutants from buildings and manufacturing of fog-free
      windows or mirrors. 

PMID- 25852356
TI  - Nano- and microsized zeolites as a perspective material for potentiometric
      biosensors creation.
AB  - A number of potentiometric biosensors based on coimmobilization of enzymes with
      different types of zeolite on pH-ion-sensitive field-effect transistor (ISFET)
      have been developed. Their working characteristics have been determined and
      compared. It was shown that clinoptilolite and zeolite Beta polymorph A (BEA) are
      more promising for creating biosensors than zeolite A. Changing the concentration
      of zeolite BEA in membranes, it is possible to extend the biosensor linear
      measurement range. The two-layer method of deposition of the enzyme with
      clinoptilolite was found to provide a significant increase in the biosensor
      sensitivity to substrates, whereas thermal modification of the zeolite BEA
      crystals can improve analytical characteristics of potentiometric biosensors for
      detection of toxic substances. These results show that it is possible to regulate
      the ISFET characteristics for different enzyme-based biosensors by tailoring the
      electrode surfaces via different zeolites. This makes zeolites strong candidates
      for integration into biosensors as ISFET modifiers. 

PMID- 25852357
TI  - Catalytic activities of noble metal atoms on WO3 (001): nitric oxide adsorption.
AB  - Using first-principles density functional theory calculations within the
      generalized gradient approximation, we investigate the adsorption of NO molecule
      on a clean WO3(001) surface as well as on the noble metal atom (Cu, Ag, and Au)
      deposited WO3(001) surfaces. We find that on a clean WO3 (001) surface, the NO
      molecule binds to the W atom with an adsorption energy (E ads) of -0.48 eV. On
      the Cu- and Ag-deposited WO3(001) surface where such noble metal atoms prefer to
      adsorb on the hollow site, the NO molecule also binds to the W atom with E ads = 
      1.69 and -1.41 eV, respectively. This relatively stronger bonding of NO to the W
      atom is found to be associated with the larger charge transfer of 0.43 e (Cu) and
      0.33 e (Ag) from the surface to adsorbed NO. However, unlike the cases of Cu
      WO3(001) and Ag-WO3(001), Au atoms prefer to adsorb on the top of W atom. On such
      an Au-WO3(001) complex, the NO molecule is found to form a bond to the Au atom
      with E ads = -1.32 eV. Because of a large electronegativity of Au atom, the
      adsorbed NO molecule captures the less electrons (0.04 e) from the surface
      compared to the Cu and Ag catalysts. Our findings not only provide useful
      information about the NO adsorption on a clean WO3(001) surface as well as on the
      noble metal atoms deposited WO3(001) surfaces but also shed light on a higher
      sensitive WO3 sensor for NO detection employing noble metal catalysts. 

PMID- 25852358
TI  - Investigation of LRS dependence on the retention of HRS in CBRAM.
AB  - The insufficient retention prevents the resistive random access memory from
      intended application, such as code storage, FPGA, encryption, and others. The
      retention characteristics of high resistance state (HRS) switching from different
      low resistance state (LRS) were investigated in a 1-kb array with one transistor
      and one resistor configuration. The HRS degradation was found strongly dependent
      on the LRS: the lower the resistance of the LRS (R LRS) is, the worse HRS
      retention will be. According to the quantum point contact model, the HRS
      corresponds to a tiny tunnel gap or neck bridge with atomic size in the filament.
      The degradation of HRS is due to the filling or widening of the neck point by the
      diffusion of copper species from the residual filament. As the residual filament
      is stronger in case of the lower R LRS, the active area around the neck point for
      copper species diffusion is larger, resulting in higher diffusion probability and
      faster degradation of HRS during the temperature-accelerated retention
      measurement. 

PMID- 25852359
TI  - Influence of post-annealing on the off current of MoS2 field-effect transistors.
AB  - Two-dimensional materials have recently been spotlighted, due to their unique
      properties in comparison with conventional bulk and thin-film materials. Among
      those materials, MoS2 is one of the promising candidates for the active layer of
      electronic devices because it shows high electron mobility and pristine band gap.
      In this paper, we focus on the evolution of the electrical property of the MoS2
      field-effect transistor (FET) as a function of post-annealing temperature. The
      results indicate that the off current drastically decreased at 200 degrees C and
      increased at 400 degrees C while other factors, such as the mobility and
      threshold voltage, show little variation. We consider that the decreasing off
      current comes from the rearrangement of the MoS2 film and the elimination of the
      surface residue. Then, the increasing off current was caused by the change of the
      material's composition and adsorption of H2O and O2. 

PMID- 25852360
TI  - Conical islands of TiO2 nanotube arrays in the photoelectrode of dye-sensitized
      solar cells.
AB  - Ti conical island structures were fabricated using photolithography and the
      reactive ion etching method. The resulting conical island structures were
      anodized in ethylene glycol solution containing 0.25 wt% NH4F and 2 vol% H2O, and
      conical islands composed of TiO2 nanotubes were successfully formed on the Ti
      foils. The conical islands composed of TiO2 nanotubes were employed in
      photoelectrodes for dye-sensitized solar cells (DSCs). DSC photoelectrodes based
      on planar Ti structures covered with TiO2 nanotubes were also fabricated as a
      reference. The short-circuit current (J sc) and efficiency of DSCs based on the
      conical island structures were higher than those of the reference samples. The
      efficiency of DSCs based on the conical island structures reached up to 1.866%.
      From electrochemical impedance spectroscopy and open-circuit voltage (V oc) decay
      measurements, DSCs based on the conical island structures exhibited a lower
      charge transfer resistance at the counter cathode and a longer electron lifetime
      at the interface of the photoelectrode and electrolyte compared to the reference
      samples. The conical island structure was very effective at improving
      performances of DSCs based on TiO2 nanotubes. Graphical AbstractConical islands
      of TiO2 nanotube arrays are fabricated by an anodizing process with Ti protruding
      dots which have a conical shape. The conical islands are applied for use in DSC
      photoelectrodes. DSCs based on the conical islands of TiO2 nanotube arrays have
      the potential to achieve higher efficiency levels compared to DSCs based on
      normal TiO2 nanotubes and TiO2 nanoparticles because the conical islands of TiO2
      nanotube arrays enlarge the surface area for dye adsorption. 

PMID- 25852361
TI  - Organic-inorganic materials containing nanoparticles of zirconium hydrophosphate
      for baromembrane separation.
AB  - Organic-inorganic membranes were obtained by stepwise modification of
      poly(ethyleneterephthalate) track membrane with nanoparticles of zirconium
      hydrophosphate. The modifier was inserted inside pores of the polymer, a size of
      which is 0.33 MUm. Inner active layer was formed by this manner. Evolution of
      morphology and functional properties of the membranes were investigated using
      methods of porosimetry, potentiometry and electron microscopy. The nanoparticles
      (4 to 10 nm) were found to form aggregates, which block pores of the polymer.
      Pores between the aggregates (4 to 8 nm) as well as considerable surface charge
      density provide significant transport numbers of counter ions (up to 0.86 for
      Na(+)). The materials were applied to baromembrane separation of corn distillery.
      It was found that precipitate is formed mainly inside the pores of the pristine
      membrane. In the case of the organic-inorganic material, the deposition occurs
      onto the outer surface and can be removed by mechanical way. Location of the
      active layer inside membranes protects it against damage. 

PMID- 25852362
TI  - Thermochemically activated carbon as an electrode material for supercapacitors.
AB  - The results of electrochemical studies of nanoporous carbon as electrode material
      for electrochemical capacitors (EC) are presented in this work. Nanoporous carbon
      material (NCM) was obtained from the raw materials of plant origin by
      carbonization and subsequent activation in potassium hydroxide. It is established
      that there is an optimal ratio of 1:1 between content of KOH and carbon material
      at chemical activation, while the maximum specific capacity of NCM is 180 F/g. An
      equivalent electrical circuit, which allows modeling of the impedance spectra in
      the frequency range of 10(-2) to 10(5) Hz, is proposed, and a physical
      interpretation of each element of the electrical circuit is presented. 

PMID- 25852363
TI  - Influence of semiconductor and metal nanoparticles on the dielectric properties
      of ionic matrix cadmium octanoate.
AB  - Dielectric properties of ionic composites consisted of cadmium octanoate matrix
      and semiconductor or metal nanoparticles have been investigated. The
      nanoparticles of different nature (semiconductor CdS, metal Au, and metal core
      semiconductor shell Au-CdS) were chemically synthesized in the smectic A phase of
      (Cd(+2)(C7H15COO)(-2), CdC8) that was used as a nanoreactor. These nanocomposites
      are very stable and well ordered; the size and shape of the nanoparticles (NPs)
      are well controlled during the synthesis. The main aim of the research was to
      examine the influence of nanoparticles on the dielectric properties of ionic
      matrix, which has smectic A ordered structure. Electrical characteristics were
      investigated at different temperatures, which correspond to different phases of
      the material. The conductivity of nanocomposites has an activation nature. The
      electrical conductivity anisotropy confirms the structural anisotropy of the
      nanocomposites. The conductivity of the nanocomposite along the cation-anion
      layers is higher by 2 orders of magnitude than that across the cation-anion
      layers. Basing on the experimental data, we proposed the simple model of the
      charge carriage process. 

PMID- 25852364
TI  - Dynamics of mass transport during nanohole drilling by local droplet etching.
AB  - Local droplet etching (LDE) utilizes metal droplets during molecular beam epitaxy
      for the self-assembled drilling of nanoholes into III/V semiconductor surfaces.
      An essential process during LDE is the removal of the deposited droplet material
      from its initial position during post-growth annealing. This paper studies the
      droplet material removal experimentally and discusses the results in terms of a
      simple model. The first set of experiments demonstrates that the droplet material
      is removed by detachment of atoms and spreading over the substrate surface.
      Further experiments establish that droplet etching requires a small arsenic
      background pressure to inhibit re-attachment of the detached atoms. Surfaces
      processed under completely minimized As pressure show no hole formation but
      instead a conservation of the initial droplets. Under consideration of these
      results, a simple kinetic scaling model of the etching process is proposed that
      quantitatively reproduces experimental data on the hole depth as a function of
      the process temperature and deposited amount of droplet material. Furthermore,
      the depth dependence of the hole side-facet angle is analyzed. 

PMID- 25852365
TI  - Biosensor for human IgE detection using shear-mode FBAR devices.
AB  - Film bulk acoustic resonators (FBARs) have been evaluated for use as biosensors
      because of their high sensitivity and small size. This study fabricated a novel
      human IgE biosensor using shear-mode FBAR devices with c-axis 23 degrees -tilted
      AlN thin films. Off-axis radio frequency (RF) magnetron sputtering method was
      used for deposition of c-axis 23 degrees -tilted AlN thin films. The deposition
      parameters were adopted as working pressure of 5 mTorr, substrate temperature of
      300 degrees C, sputtering power of 250 W, and 50 mm distance between off-axis and
      on-axis. The characteristics of the AlN thin films were investigated by X-ray
      diffraction and scanning electron microscopy. The frequency response was measured
      with an HP8720 network analyzer with a CASCADE probe station. The X-ray
      diffraction revealed (002) preferred wurtzite structure, and the cross-sectional
      image showed columnar structure with 23 degrees -tilted AlN thin films. In the
      biosensor, an Au/Cr layer in the FBAR backside cavity was used as the detection
      layer and the Au surface was modified using self-assembly monolayers (SAMs)
      method. Then, the antigen and antibody were coated on biosensor through their
      high specificity property. Finally, the shear-mode FBAR device with k t (2) of
      3.18% was obtained, and the average sensitivity for human IgE detection of about
      1.425 * 10(5) cm(2)/g was achieved. 

PMID- 25852366
TI  - High-performance HfO x /AlO y -based resistive switching memory cross-point array
      fabricated by atomic layer deposition.
AB  - Resistive switching memory cross-point arrays with TiN/HfO x /AlO y /Pt structure
      were fabricated. The bi-layered resistive switching films of 5-nm HfO x and 3-nm
      AlO y were deposited by atomic layer deposition (ALD). Excellent device
      performances such as low switching voltage, large resistance ratio, good cycle-to
      cycle and device-to-device uniformity, and high yield were demonstrated in the
      fabricated 24 by 24 arrays. In addition, multi-level data storage capability and
      robust reliability characteristics were also presented. The achievements
      demonstrated the great potential of ALD-fabricated HfO x /AlO y bi-layers for the
      application of next-generation nonvolatile memory. 

PMID- 25852367
TI  - Pure electron-electron dephasing in percolative aluminum ultrathin film grown by
      molecular beam epitaxy.
AB  - We have successfully grown ultrathin continuous aluminum film by molecular beam
      epitaxy. This percolative aluminum film is single crystalline and strain free as
      characterized by transmission electron microscopy and atomic force microscopy.
      The weak anti-localization effect is observed in the temperature range of 1.4 to
      10 K with this sample, and it reveals that, for the first time, the dephasing is
      purely caused by electron-electron inelastic scattering in aluminum. 

PMID- 25852368
TI  - Metal nanoparticle-enhanced photocurrent in GaAs photovoltaic structures with
      microtextured interfaces.
AB  - The photocurrent enhancement effect caused by Au and Ag nanoparticles for GaAs
      based photovoltaic structures of surface barrier or p-n junction type with
      microtextured interfaces has been investigated in dependence on the conditions of
      nanoparticles deposition and, respectively, on the shape and local dielectric
      environment of obtained nanoparticle arrays. Three nanoparticle deposition
      methods have been checked: 1) photoinduced chemical deposition of Au from aqueous
      AuCl3 solution forming nanowires on the ridges of quasigrating-type surface
      microrelief, 2) deposition of Ag nanoparticles from colloidal suspension on the
      GaAs substrate covered with poly(vinylpyridine), and 3) drop and dry deposition
      of Au/SiO2 core-shell nanoparticles from aqueous colloid solution. The
      comprehensive investigation of optical reflectance, photoelectric, and electrical
      characteristics of the fabricated barrier structures has shown the highest
      photovoltaic parameters for surface microrelief of quasigrating-type and
      electroless Au nanoparticle deposition. The analysis of characteristics obtained
      allowed us also to define the mechanisms of the total photocurrent enhancement. 

PMID- 25852369
TI  - Influence of crystal structure of nanosized ZrO2 on photocatalytic degradation of
      methyl orange.
AB  - Nanosized ZrO2 powders with near pure monoclinic, tetragonal, and cubic
      structures synthesized by various methods were used as catalysts for
      photocatalytic degradation of methyl orange. The structural and textural
      properties of the samples were analyzed by X-ray diffraction, Raman spectroscopy,
      TEM, UV-vis, X-ray photoelectron spectroscopy (XPS), and N2 adsorption
      measurements. The performance of synthesized ZrO2 nanoparticles in the
      photocatalytic degradation of methyl orange under UV light irradiation was
      evaluated. The photocatalytic activity of the pure monoclinic ZrO2 sample is
      higher than that of the tetragonal and cubic ZrO2 samples under optimum identical
      conditions. The characterization results revealed that monoclinic ZrO2
      nanoparticles possessed high crystallinity and mesopores with diameter of 100 A.
      The higher activity of the monoclinic ZrO2 sample for the photocatalytic
      degradation of methyl orange can be attributed to the combining effects of
      factors including the presence of small amount of oxygen-deficient zirconium
      oxide phase, high crystallinity, large pores, and high density of surface
      hydroxyl groups. 

PMID- 25852370
TI  - A facile approach to prepare silicon-based Pt-Ag tubular dendritic nano-forests
      (tDNFs) for solar-light-enhanced methanol oxidation reaction.
AB  - In this paper, a facile two-step Galvanic replacement reaction (GRR) is proposed
      to prepare Pt-Ag tubular dendritic nano-forests (tDNFs) in ambient condition for
      enhancing methanol oxidation reaction (MOR) under solar illumination. In the
      first GRR, a homogeneous layer of silver dendritic nano-forests (DNFs) with 10
      MUm in thickness was grown on Si wafer in 5 min in silver nitride (AgNO3) and
      buffer oxide etchant (BOE) solution. In the second GRR, we utilized
      chloroplatinic acid (H2PtCl6) as the precursor for platinum (Pt) deposition to
      further transform the prepared Ag DNFs into Pt-Ag tDNFs. The catalytic
      performance and solar response of the Pt-Ag tDNFs toward methanol electro
      oxidation are also studied by cyclic voltammetry (CV) and chronoamperometry (CA).
      The methanol oxidation current was boosted by 6.4% under solar illumination on
      the Pt-Ag tDNFs due to the induced localized surface plasmon resonance (LSPR) on
      the dendritic structure. Current results provide a cost-effective and facile
      approach to prepare solar-driven metallic electrodes potentially applicable to
      photo-electro-chemical fuel cells. 

PMID- 25852371
TI  - Effects of doping and annealing on properties of ZnO films grown by atomic layer
      deposition.
AB  - Undoped and Al-doped ZnO films were synthesized by atomic layer deposition at 150
      degrees C and then annealed at 350 degrees C in different atmospheres. Effects of
      doping and annealing on the film growth mode and properties were investigated.
      The undoped film has strong UV emission and weak Zn interstitial emission.
      Annealing introduces O vacancies, decreases Zn interstitials, and results in
      weakening and blue-shifting of the UV emission which is sensitive to annealing
      atmosphere. Al doping induces the film growing with its c-axis parallel to the
      substrate surface. It also introduces non-radiative centers and weakens the UV
      emission. Al doping widens the film bandgap, which has a quadratic dependence on
      Al content. Al doping decreases the film resistivity to 5.3 * 10(-3) Omega . cm.
      Annealing has little effect on photoluminescence of the doped films, but it
      degrades undoped and doped ZnO film conductivity dramatically; and the
      degradation depends on the annealing ambient. 

PMID- 25852372
TI  - Transparent and flexible capacitors based on nanolaminate Al2O3/TiO2/Al2O3.
AB  - Transparent and flexible capacitors based on nanolaminate Al2O3/TiO2/Al2O3
      dielectrics have been fabricated on indium tin oxide-coated polyethylene
      naphthalate substrates by atomic layer deposition. A capacitance density of 7.8
      fF/MUm(2) at 10 KHz was obtained, corresponding to a dielectric constant of 26.3.
      Moreover, a low leakage current density of 3.9 * 10(-8) A/cm(2) at 1 V has been
      realized. Bending test shows that the capacitors have better performances in
      concave conditions than in convex conditions. The capacitors exhibit an average
      optical transmittance of about 70% in visible range and thus open the door for
      applications in transparent and flexible integrated circuits. 

PMID- 25852373
TI  - Positronics of subnanometer atomistic imperfections in solids as a high
      informative structure characterization tool.
AB  - Methodological possibilities of positron annihilation lifetime (PAL) spectroscopy
      applied to characterize different types of nanomaterials treated within three
      term fitting procedure are critically reconsidered. In contrast to conventional
      three-term analysis based on admixed positron- and positronium-trapping modes,
      the process of nanostructurization is considered as substitutional positron
      positronium trapping within the same host matrix. Developed formalism allows
      estimate interfacial void volumes responsible for positron trapping and
      characteristic bulk positron lifetimes in nanoparticle-affected inhomogeneous
      media. This algorithm was well justified at the example of thermally induced
      nanostructurization occurring in 80GeSe2-20Ga2Se3 glass. 

PMID- 25852374
TI  - Local structure and paramagnetic properties of the nanostructured carbonaceous
      material shungite.
AB  - Using a scanning electron microscopy, elemental analysis, electron paramagnetic
      resonance, and Raman scattering methods, two types of the shungite materials (Sh
      II from Zazhogino deposit and shungite from a commercial filter (ShF)), with
      different carbon content and porosity, are studied in this work. It was
      established by scanning electron microscopy data that the structure of the
      shungite samples is formed by a micron-size agglomeration of carbon and silicon
      dioxide clusters. It is found from the Raman data that carbon fraction is formed
      from sp(2)-hybridized clusters, size of which increases from 9 up to 12 nm after
      annealing of the samples. High conductivity of shungite is found to belong to the
      carbon nanoclusters of different sizes. Big clusters give the conduction electron
      spin resonance signal with a Dysonian line shape with variable g-factor and line
      width. The careful search of the nature of two other narrow electron paramagnetic
      resonance signals in shungite, which used to be prescribed to fullerene-like
      molecules, is fulfilled. Here, it is shown that the oxygen-deficient E'gamma
      centers are responsible for these signals. A strong correlation is revealed
      between the concentration of E'gamma centers and the line width of conduction
      electron spin resonance signal, which occurs under annealing process of the
      samples at T = 570 K. The correlation reasons are a spin-spin coupling between
      two spin subsystems and time dependent of the E'gamma concentration during
      annealing process. 

PMID- 25852375
TI  - Study of parasitic resistance effects in nanowire and nanoribbon biosensors.
AB  - In this work, we investigate sensor design approaches for eliminating the effects
      of parasitic resistance in nanowire and nanoribbon biosensors. Measurements of pH
      with polysilicon nanoribbon biosensors are used to demonstrate a reduction in
      sensitivity as the sensor length is reduced. The sensitivity (normalised
      conductance change) is reduced from 11% to 5.5% for a pH change from 9 to 3 as
      the sensing window length is reduced from 51 to 11 MUm. These results are
      interpreted using a simple empirical model, which is also used to demonstrate how
      the sensitivity degradation can be alleviated by a suitable choice of sensor
      window length. Furthermore, a differential sensor design is proposed that
      eliminates the detrimental effects of parasitic resistance. Measurements on the
      differential sensor give a sensitivity of 15%, which is in good agreement with
      the predicted maximum sensitivity obtained from modeling. 

PMID- 25852376
TI  - Nucleation and growth of primary nanostructures in SrTiO3 homoepitaxy.
AB  - SrTiO3 nanoislands on SrTiO3 (001) in a diffusion-limited growth regime were
      studied using in situ scanning tunneling microscopy (STM). The STM images
      revealed two characteristic features of nucleation stages. First, the minimum
      lateral size of the one-unit-cell (uc)-high SrTiO3 islands was 4 * 4 uc (2).
      Second, one-dimensional SrTiO3 islands of a 4 uc width grew along the crystal
      symmetry directions. These observations suggest that 4 * 4-uc (2) islands act as
      a minimum nucleation seed, and the addition of SrTiO3 molecular species of the
      same width is the primary and dominant growth process in SrTiO3 homoepitaxy. A
      close inspection of the surface of the substrate during the deposition process
      revealed possible connections between surface reconstruction and energetically
      favorable nucleation of SrTiO3 islands. 

PMID- 25852377
TI  - Enhancement of polymer endurance to UV light by incorporation of semiconductor
      nanoparticles.
AB  - Improvement of polyvinyl alcohol stability against ultraviolet (UV) illumination
      is achieved by introducing cadmium sulfide (CdS) nanoparticles into the polymeric
      matrix. Enhancement of stability is analyzed by optical characterization methods.
      UV protection is achieved by diminishing the probability of photo-activated
      formation of defects in polymer. The sources of polymer protection are the
      lowering of the efficiency of polymer excitation via partial absorption of
      incident light by the embedded nanoparticles as well as the de-excitation of the
      macromolecules that have already absorbed UV quanta via energy drain to
      nanoparticles. Within the nanoparticles, the energy is either dissipated by
      conversion to the thermal energy or reemitted as visible-range photoluminescence
      quanta. 

PMID- 25852378
TI  - Composites of silica with immobilized cholinesterase incorporated into polymeric
      shell.
AB  - Synthetic approaches for new nanocomposite materials with relatively high
      cholinesterase activity have been developed. The peculiarity of the formation of
      such systems is the introduction of cholinesterase into polymer with subsequent
      incorporation on the ready-made silica particles and into the polysiloxane
      matrixes during sol-gel synthesis. Evaluation of the cholinesterase activity has
      been fulfilled through the imitation of the acetylcholine chloride decomposition
      reaction. Values of activity for cholinesterase nanocomposites demonstrated in
      this work are higher than those for the native cholinesterase. The higher
      activity of cholinesterase contained in nanocomposites was found for those
      prepared using highly dispersed silica. 

PMID- 25852379
TI  - The nanostructuring of surfaces and films using interference lithography and
      chalcogenide photoresist.
AB  - The reversible and transient photostimulated structural changes in annealed
      chalcogenide glass (ChG) layers were used to form interference periodic
      structures on semiconductor surfaces and metal films. It was shown that negative
      action etchants based on amines dissolve illuminated parts of a chalcogenide
      film, i.e., act as positive etchants. The diffraction gratings and 2-D
      interference structures on germanium ChGs - more environmentally acceptable
      compounds than traditionally used arsenic chalcogenides - were recorded, and
      their characteristics were studied. 

PMID- 25852380
TI  - Bimetallic core/shell nanoparticle-decorated 3D urchin-like hierarchical TiO2
      nanostructures with magneto-responsive and decolorization characteristics.
AB  - The semiconductors decorated with noble metals or magnetic metals have attracted
      increasing attention due to multifunctional properties. In this article, we
      prepare novel bimetallic core/shell nanoparticle (Co@Au and Co@Ag)-decorated 3D
      urchin-like hierarchical TiO2 nanostructures through combining electroless
      plating and in situ replacement processes. The morphology and structure are
      characterized by scanning electron microscopy, transmission electron microscopy,
      energy-dispersive spectroscopy, and a surface area analyzer. It demonstrates that
      Co@Au and Co@Ag nanoparticles are uniformly decorated on urchin-like TiO2
      nanostructures. The composite nanostructures show not only surface plasmon
      absorption band from Au or Ag but also a magneto-responsive characteristic from
      Co. This allows composite nanostructures to exhibit advantages including enhanced
      decolorization efficiency compared to pure TiO2 nanostructures and facile
      separation from a solution by magnetic field. 

PMID- 25852381
TI  - Fabrication and characterization of GaN-based light-emitting diodes without pre
      activation of p-type GaN.
AB  - We fabricated GaN-based light-emitting diodes (LEDs) without pre-activation of p
      type GaN. During the fabrication process, a 100-nm-thick indium tin oxide film
      was served as the p-type contact layer and annealed at 500 degrees C in N2
      ambient for 20 min to increase its transparency as well as to activate the p-type
      GaN. The electrical measurements showed that the LEDs were featured by a lower
      forward voltage and higher wall-plug efficiency in comparison with LEDs using pre
      activation of p-type GaN. We discussed the mechanism of activation of p-type GaN
      at 500 degrees C in N2 ambient. Furthermore, x-ray photoemission spectroscopy
      examinations were carried out to study the improved electrical performances of
      the LEDs without pre-activation of p-type GaN. 

PMID- 25852382
TI  - The phase transformation of CuInS2 from chalcopyrite to wurtzite.
AB  - In the present work, CuInS2 nanoparticles have been successfully synthesized by
      water-bath method with deionized water as solvent and thioglycolic acid as
      complexing agent at 80 degrees C. The phase transition of CuInS2 from
      chalcopyrite to wurtzite was realized by adjusting the pH value of reaction
      solution. The emergence of Cu2S in the condition of higher pH value of reaction
      solution led to the formation of wurtzite CuInS2. This facile method that
      controls the phase structure by adjusting the solution pH value could open a new
      way to synthesize other I-III-VI2 ternary semiconductor compounds. 

PMID- 25852383
TI  - Synthesis and adsorption properties of chitosan-silica nanocomposite prepared by
      sol-gel method.
AB  - A hybrid nanocomposite material has been obtained by in situ formation of an
      inorganic network in the presence of a preformed organic polymer. Chitosan
      biopolymer and tetraethoxysilane (TEOS), which is the most common silica
      precursor, were used for the sol-gel reaction. The obtained composite chitosan
      silica material has been characterized by physicochemical methods such as
      differential thermal analyses (DTA); carbon, hydrogen, and nitrogen (CHN)
      elemental analysis; nitrogen adsorption/desorption isotherms, scanning electron
      microscopy (SEM); and Fourier transform infrared (FTIR) spectroscopy to determine
      possible interactions between silica and chitosan macromolecules. Adsorption of
      microquantities of V(V), Mo(VI), and Cr(VI) oxoanions from the aqueous solutions
      by the obtained composite has been studied in comparison with the chitosan beads,
      previously crosslinked with glutaraldehyde. The adsorption capacity and kinetic
      sorption characteristics of the composite material were estimated. 

PMID- 25852384
TI  - Investigations of ripple pattern formation on Germanium surfaces using 100-keV
      Ar(+) ions.
AB  - We have investigated the formation of nanoripples on the surface of germanium,
      Ge(100), due to the effect of 100-keV Ar (+) ion irradiation. The irradiation was
      carried out at different incidence angles from 0 degrees  to 75 degrees  in steps
      of 15 degrees  with respect to the surface normal with a fixed ion fluence of
      approximately 3 * 10(17) ions/cm(2). Atomic force micrographs show an increase in
      surface roughness from 0.5 to 4.3 nm for the pristine sample and the sample
      irradiated at 60 degrees  incidence angle due to cos(-1)(theta) dependence on
      sputtering yield. With increase in angle of incidence, there is transition
      observed from nanodots to aligned nanodots perpendicular to the direction of the
      beam. There is an increase in size of the nanostructures observed from 44 to 103
      nm with angle of incidence. The formation of nanoripples initiates at an angle of
      theta ~ 45 degrees . Ripple pattern formation has taken place on the Ge surface
      in the energy regime of 100 keV as compared to the other reports which had been
      carried out using very low energy ions. Raman spectra reveal that the near
      surface of crystalline Ge samples becomes amorphous due to interaction of Ar(+)
      ions due to creation of defects through collision cascades. 

PMID- 25852385
TI  - Phase-change properties of GeSbTe thin films deposited by plasma-enchanced atomic
      layer depositon.
AB  - Phase-change access memory (PCM) appears to be the strongest candidate for next
      generation high-density nonvolatile memory. The fabrication of ultrahigh-density
      PCM depends heavily on the thin-film growth technique for the phase-changing
      chalcogenide material. In this study, Ge2Sb2Te5 (GST) and GeSb8Te thin films were
      deposited by plasma-enhanced atomic layer deposition (ALD) method using Ge
      [(CH3)2 N]4, Sb [(CH3)2 N]3, Te(C4H9)2 as precursors and plasma-activated H2 gas
      as reducing agent of the metallorganic precursors. Compared with GST-based
      device, GeSb8Te-based device exhibits a faster switching speed and reduced reset
      voltage, which is attributed to the growth-dominated crystallization mechanism of
      the Sb-rich GeSb8Te films. These results show that ALD is an attractive method
      for preparation of phase-change materials. 

PMID- 25852386
TI  - High-performance flexible Ag nanowire electrode with low-temperature atomic-layer
      deposition fabrication of conductive-bridging ZnO film.
AB  - As material for flexible transparent electrodes for organic photoelectric
      devices, the silver nanowires (AgNWs) have been widely studied. In this work, we
      propose a hybrid flexible anode with photopolymer substrate, which is composed of
      spin-coating-processed AgNW meshes and of zinc oxide (ZnO) prepared by low
      temperature (60 degrees C) atomic layer deposition. ZnO effectively fills in the
      voids of the AgNW mesh electrode, which is thus able to contact to the device all
      over the active area, to allow for efficient charge extraction/injection.
      Furthermore, ZnO grown by low temperature mainly relies on hole conduction to
      make the anode play a better role. Hole-only devices are fabricated to certify
      the functionality of the low-temperature ZnO film. Finally, we confirm that the
      ZnO film grown at a low temperature bring a significant contribution to the
      performance of the modified AgNW anode. 

PMID- 25852387
TI  - The function of a 60-nm-thick AlN buffer layer in n-ZnO/AlN/p-Si(111).
AB  - ZnO films were prepared on p-Si (111) substrates by using atomic layer
      deposition. High-resolution x-ray diffraction (XRD), scanning electron microscopy
      (SEM), x-ray photoelectron spectroscopy (XPS), photoluminescence (PL), and I-V
      measurements were carried out to characterize structural, electrical, and optical
      properties. After introducing a 60-nm-thick AlN buffer layer, the growth
      direction of the ZnO films was changed from [10] to [0002]. Meanwhile, the ZnO
      crystalline quality was significantly improved as verified by both XRD and PL
      analyses. It has been demonstrated that the reverse leakage current was greatly
      reduced with the AlN buffer layer. The valence band offsets have been determined
      to be 3.06, 2.95, and 0.83 eV for ZnO/Si, ZnO/AlN, and AlN/Si heterojunctions,
      respectively, and the band alignment of ZnO/Si heterojunction was modified to be
      0.72 eV after introducing the AlN buffer layer. Our work offered a potential way
      to fabricate Si-based ultraviolet light-emitting diodes and improve the device
      performances. 

PMID- 25852388
TI  - Combination of inverted pyramidal nanovoid with silver nanoparticles to obtain
      further enhancement and its detection for ricin.
AB  - We have obtained the surface-enhanced Raman scattering substrate by depositing
      silver nanoparticles on the surface of the inverted pyramidal nanovoid in order
      to improve the enhance effects. Experimental results showed that the combined
      substrate exhibited greater enhancement than the nanovoid substrate or
      nanoparticles. In order to test the SERS activity of the combined substrates,
      Rh6G and ricin toxin were used as Raman probes. Finite element method was
      employed to simulate electric field and induced charge distribution of the
      substrates, which have been used to explore the interaction between nanoparticles
      and nanovoid as well as mechanism of the great enhancement. 

PMID- 25852389
TI  - Investigation on the passivated Si/Al2O3 interface fabricated by non-vacuum
      spatial atomic layer deposition system.
AB  - Currently, aluminum oxide stacked with silicon nitride (Al2O3/SiNx:H) is a
      promising rear passivation material for high-efficiency P-type passivated emitter
      and rear cell (PERC). It has been indicated that atomic layer deposition system
      (ALD) is much more suitable to prepare high-quality Al2O3 films than plasma
      enhanced chemical vapor deposition system and other process techniques. In this
      study, an ultrafast, non-vacuum spatial ALD with the deposition rate of around 10
      nm/min, developed by our group, is hired to deposit Al2O3 films. Upon post
      annealing for the Al2O3 films, the unwanted delamination, regarded as blisters,
      was found by an optical microscope. This may lead to a worse contact within the
      Si/Al2O3 interface, deteriorating the passivation quality. Thin stoichiometric
      silicon dioxide films prepared on the Si surface prior to Al2O3 fabrication
      effectively reduce a considerable amount of blisters. The residual blisters can
      be further out-gassed when the Al2O3 films are thinned to 8 nm and annealed above
      650 degrees C. Eventually, the entire PERC with the improved triple-layer
      SiO2/Al2O3/SiNx:H stacked passivation film has an obvious gain in open-circuit
      voltage (V oc) and short-circuit current (J sc) because of the increased minority
      carrier lifetime and internal rear-side reflectance, respectively. The electrical
      performance of the optimized PERC with the V oc of 0.647 V, J sc of 38.2
      mA/cm(2), fill factor of 0.776, and the efficiency of 19.18% can be achieved. 

PMID- 25852390
TI  - A new strategy for TiO2 whiskers mediated multi-mode cancer treatment.
AB  - Traditional Chinese medicine (TCM) which functions as chemotherapeutic or
      adjuvantly chemotherapeutic agents has been drawing a great many eyeballs for its
      easy obtain and significant antitumor effects accompanied with less toxic and
      side effects. PDT (photodynamic therapy) utilizes the fact that certain compounds
      coined as photosensitizers, when exposed to light of a specific wavelength, are
      capable of generating cytotoxic reactive oxygen species (ROS) such as hydroxyl
      radical, hydrogen peroxide, and superoxide to kill cancer cells. Combinations of
      cancer therapeutic modalities are studied to improve the efficacy of treatment.
      This study aimed to explore a new strategy of coupling of titanium dioxide
      whiskers (TiO2 Ws) with the anticancer drug gambogic acid (GA) in photodynamic
      therapy. The nanocomposites were coined as GA-TiO2. The combination of TiO2 Ws
      with GA induced a remarkable enhancement in antitumor activity estimated by MTT
      assay, nuclear DAPI staining, and flow cytometry. Furthermore, the possible
      signaling pathway was explored by reverse transcription polymerase chain reaction
      (RT-PCR) and Western blot assay. These results identify TiO2 Ws of good
      biocompatibility and photocatalytic activity. In human leukemia cells (K562
      cells), TiO2 Ws could obviously increase the intracellular concentration of GA
      and enhance its potential antitumor efficiency, suggesting that TiO2 Ws could act
      as an efficient drug delivery carrier targeting GA to carcinoma cells. Moreover,
      photodynamic GA-TiO2 nanocomposites could induce an evident reinforcement in
      antitumor activity with UV illumination. These results reveal that such modality
      combinations put forward a promising proposal in cancer therapy. 

PMID- 25852391
TI  - Structure and photoluminescence of the TiO2 films grown by atomic layer
      deposition using tetrakis-dimethylamino titanium and ozone.
AB  - TiO2 films were grown on silicon substrates by atomic layer deposition (ALD)
      using tetrakis-dimethylamino titanium and ozone. Amorphous TiO2 film was
      deposited at a low substrate temperature of 165 degrees C, and anatase TiO2 film
      was grown at 250 degrees C. The amorphous TiO2 film crystallizes to anatase TiO2
      phase with annealing temperature ranged from 300 degrees C to 1,100 degrees C in
      N2 atmosphere, while the anatase TiO2 film transforms into rutile phase at a
      temperature of 1,000 degrees C. Photoluminescence from anatase TiO2 films
      contains a red band at 600 nm and a green band at around 515 nm. The red band
      exhibits a strong correlation with defects of the under-coordinated Ti(3+) ions,
      and the green band shows a close relationship with the oxygen vacancies on (101)
      oriented anatase crystal surface. A blue shift of the photoluminescence spectra
      reveals that the defects of under-coordinated Ti(3+) ions transform to surface
      oxygen vacancies in the anatase TiO2 film annealing at temperature from 800
      degrees C to 900 degrees C in N2 atmosphere. 

PMID- 25852392
TI  - Crystallographic orientation-dependent pattern replication in direct imprint of
      aluminum nanostructures.
AB  - In the present work, we perform molecular dynamics simulations corroborated by
      experimental validations to elucidate the underlying deformation mechanisms of
      single-crystalline aluminum under direct imprint using a rigid silicon master. We
      investigate the influence of crystallographic orientation on the microscopic
      deformation behavior of the substrate materials and its correlation with the
      macroscopic pattern replications. Furthermore, the surface mechanical properties
      of the patterned structures are qualitatively characterized by nanoindentation
      tests. Our results reveal that dislocation slip and deformation twinning are two
      primary plastic deformation modes of single-crystalline aluminum under the direct
      imprint. However, both the competition between the individual deformation
      mechanisms and the geometry between activated dislocation slip systems and
      imprinted surface vary with surface orientation, which in turn leads to a strong
      crystallographic orientation dependence of the pattern replications. It is found
      that the (010) orientation leads to a better quality of pattern replication of
      single-crystalline aluminum than the (111) orientation. 

PMID- 25852393
TI  - Angular shaping of fluorescence from synthetic opal-based photonic crystal.
AB  - Spectral, angular, and temporal distributions of fluorescence as well as specular
      reflection were investigated for silica-based artificial opals. Periodic
      arrangement of nanosized silica globules in the opal causes a specific dip in the
      defect-related fluorescence spectra and a peak in the reflectance spectrum. The
      spectral position of the dip coincides with the photonic stop band. The latter is
      dependent on the size of silica globules and the angle of observation. The
      spectral shape and intensity of defect-related fluorescence can be controlled by
      variation of detection angle. Fluorescence intensity increases up to two times at
      the edges of the spectral dip. Partial photobleaching of fluorescence was
      observed. Photonic origin of the observed effects is discussed. 

PMID- 25852394
TI  - The effect of silver nanoparticles (AgNPs) on proliferation and apoptosis of in
      ovo cultured glioblastoma multiforme (GBM) cells.
AB  - Recently, it has been shown that silver nanoparticles (AgNPs) provide a unique
      approach to the treatment of tumors, especially those of neuroepithelial origin.
      Thus, the aim of this study was to evaluate the impact of AgNPs on proliferation
      and activation of the intrinsic apoptotic pathway of glioblastoma multiforme
      (GBM) cells cultured in an in ovo model. Human GBM cells, line U-87, were placed
      on chicken embryo chorioallantoic membrane. After 8 days, the tumors were divided
      into three groups: control (non-treated), treated with colloidal AgNPs (40
      MUg/ml), and placebo (tumors supplemented with vehicle only). At the end of the
      experiment, all tumors were isolated. Assessment of cell proliferation and cell
      apoptosis was estimated by histological, immunohistochemical, and Western blot
      analyses. The results show that AgNPs can influence GBM growth. AgNPs inhibit
      proliferation of GBM cells and seem to have proapoptotic properties. Although
      there were statistically significant differences between control and AgNP groups
      in the AI and the levels of active caspase 9 and active caspase 3, the level of
      these proteins in GBM cells treated with AgNPs seems to be on the border between
      the spontaneous apoptosis and the induced. Our results indicate that the
      antiproliferative properties of silver nanoparticles overwhelm proapoptotic ones.
      Further research focused on the cytotoxic effect of AgNPs on tumor and normal
      cells should be conducted. 

PMID- 25852395
TI  - Au nanostructure arrays for plasmonic applications: annealed island films versus
      nanoimprint lithography.
AB  - This paper attempts to compare the main features of random and highly ordered
      gold nanostructure arrays (NSA) prepared by thermally annealed island film and
      nanoimprint lithography (NIL) techniques, respectively. Each substrate possesses
      different morphology in terms of plasmonic enhancement. Both methods allow such
      important features as spectral tuning of plasmon resonance position depending on
      size and shape of nanostructures; however, the time and cost is quite different.
      The respective comparison was performed experimentally and theoretically for a
      number of samples with different geometrical parameters. Spectral characteristics
      of fabricated NSA exhibited an expressed plasmon peak in the range from 576 to
      809 nm for thermally annealed samples and from 606 to 783 nm for samples prepared
      by NIL. Modelling of the optical response for nanostructures with typical shapes
      associated with these techniques (parallelepiped for NIL and semi-ellipsoid for
      annealed island films) was performed using finite-difference time-domain
      calculations. Mathematical simulations have indicated the dependence of electric
      field enhancement on the shape and size of the nanoparticles. As an important
      point, the distribution of electric field at so-called 'hot spots' was
      considered. Parallelepiped-shaped nanoparticles were shown to yield maximal
      enhancement values by an order of magnitude greater than their semi-ellipsoid
      shaped counterparts; however, both nanoparticle shapes have demonstrated
      comparable effective electrical field enhancement values. Optimized Au
      nanostructures with equivalent diameters ranging from 85 to 143 nm and height
      equal to 35 nm were obtained for both techniques, resulting in the largest
      electrical field enhancement. The application of island film thermal annealing
      method for nanochips fabrication can be considered as a possible cost-effective
      platform for various surface-enhanced spectroscopies; while the NIL-fabricated
      NSA looks like more effective for sensing of small-size objects. 

PMID- 25852396
TI  - Room-temperature electrically pumped near-infrared random lasing from high
      quality m-plane ZnO-based metal-insulator-semiconductor devices.
AB  - Epitaxial m-plane ZnO thin films have been deposited on m-plane sapphire
      substrates at a low temperature of 200 degrees C by atomic layer deposition. A 90
      degrees  in-plane rotation is observed between the m-plane ZnO thin films and the
      sapphire substrates. Moreover, the residual strain along the ZnO [-12-10]
      direction is released. To fabricate metal-insulator-semiconductor devices, a 50
      nm Al2O3 thin film is deposited on the m-plane ZnO thin films. It is interesting
      to observe the near-infrared random lasing from the metal-insulator-semiconductor
      devices. 

PMID- 25852397
TI  - Photoinduced refractive index variation within picosecond laser pulses excitation
      as the indicator of oxyorthosilicates single crystals composition modification.
AB  - For the first time, the diagnostics of oxyorthosilicates single crystals based on
      self-action of picosecond range laser pulses at 1,064 nm (1.17 eV) has been
      performed. High sensitivity of the photoinduced refractive index variation to the
      substitution of the Lu atoms by Gd in the LSO/LGSO crystalline host as well as to
      the admixture of Ce was found. The effect can be explained with different
      electron detrapping-recombination process efficiencies due to the resonant
      electron excitation from the deep traps in the gap attributed to intrinsic oxygen
      vacancies. 

PMID- 25852398
TI  - Enhanced performance of photonic crystal GaN light-emitting diodes with graphene
      transparent electrodes.
AB  - The two-dimensional (2D) triangle lattice air hole photonic crystal (PC) GaN
      based light-emitting diodes (LED) with double-layer graphene transparent
      electrodes (DGTE) have been produced. The current spreading effect of the double
      layer graphene (GR) on the surface of the PC structure of the LED has been
      researched. Specially, we found that the part of the graphene suspending over the
      air hole of the PC structure was of much higher conductivity, which reduced the
      average sheet resistance of the graphene transparent conducting electrode and
      improved the current spreading of the PC LED. Therefore, the work voltage of the
      DGTE-PC LED was obviously decreased, and the output power was greatly enhanced.
      The COMSOL software was used to simulate the current density distribution of the
      samples. The results show that the etching of PC structure results in the
      degradation of the current spreading and that the graphene transparent conducting
      electrode can offer an uniform current spreading in the DGTE-PC LED. PACS:
      85.60.Jb; 68.65.Pq; 42.70.Qs.

PMID- 25852399
TI  - Nitrogen-doped, FeNi alloy nanoparticle-decorated graphene as an efficient and
      stable electrode for electrochemical supercapacitors in acid medium.
AB  - Nitrogen-doped graphene decorated by iron-nickel alloy is introduced as a
      promising electrode material for supercapacitors. Compared to pristine and Ni
      decorated graphene, in acid media, the introduced electrode revealed excellent
      specific capacitance as the corresponding specific capacitance was multiplied
      around ten times with capacity retention maintained at 94.9% for 1,000 cycles.
      Briefly, iron acetate, nickel acetate, urea, and graphene oxide were
      ultrasonicated and subjected to MW heating and then sintered with melanin in Ar.
      The introduced N-doped FeNi@Gr exhibits remarkable electrochemical behavior with
      long-term stability. 

PMID- 25852400
TI  - Acute oral toxicity and biodistribution study of zinc-aluminium-levodopa
      nanocomposite.
AB  - Layered double hydroxide (LDH) is an inorganic-organic nano-layered material that
      harbours drug between its two-layered sheets, forming a sandwich-like structure.
      It is attracting a great deal of attention as an alternative drug delivery
      (nanodelivery) system in the field of pharmacology due to their relative low
      toxic potential. The production of these nanodelivery systems, aimed at improving
      human health through decrease toxicity, targeted delivery of the active compound
      to areas of interest with sustained release ability. In this study, we
      administered zinc-aluminium-LDH-levodopa nanocomposite (ZAL) and zinc-aluminium
      nanocomposite (ZA) to Sprague Dawley rats to evaluate for acute oral toxicity
      following OECD guidelines. The oral administration of ZAL and ZA at a limit dose
      of 2,000 mg/kg produced neither mortality nor acute toxic signs throughout 14
      days of the observation. The percentage of body weight gain of the animals showed
      no significant difference between control and treatment groups. Animal from the
      two treated groups gained weight continuously over the study period, which was
      shown to be significantly higher than the weight at the beginning of the study (P
      < 0.05). Biochemical analysis of animal serum showed no significant difference
      between rats treated with ZAL, ZA and controls. There was no gross lesion or
      histopathological changes observed in vital organs of the rats. The results
      suggested that ZAL and ZA at 2,000 mg/kg body weight in rats do not induce acute
      toxicity in the animals. Elemental analysis of tissues of treated animals
      demonstrated the wider distribution of the nanocomposite including the brain. In
      summary, findings of acute toxicity tests in this study suggest that zinc
      aluminium nanocomposite intercalated with and the un-intercalated were safe when
      administered orally in animal models for short periods of time. It also
      highlighted the potential distribution ability of Tween-80 coated nanocomposite
      after oral administration. 

PMID- 25852401
TI  - Ag nanoparticles-decorated ZnO nanorod array on a mechanical flexible substrate
      with enhanced optical and antimicrobial properties.
AB  - Heteronanostructured zinc oxide nanorod (ZnO NR) array are vertically grown on
      polydimethylsiloxane (PDMS) through a hydrothermal method followed by an in situ
      deposition of silver nanoparticles (Ag NPs) through a photoreduction process. The
      Ag-ZnO heterostructured nanorods on PDMS are measured with an average diameter of
      160 nm and an average length of 2 MUm. ZnO NRs measured by high-resolution
      transmission electron microscope (HRTEM) shows highly crystalline with a lattice
      fringe of 0.255 nm, which corresponds to the (0002) planes in ZnO crystal
      lattice. The average diameter of the Ag NPs in situ deposited on the ZnO NRs is
      estimated at 22 +/- 2 nm. As compared to the bare ZnO NRs, the heterostructured
      Ag-ZnO nanorod array shows enhanced ultraviolet (UV) absorption at 440 nm, and
      significant emission in the visible region (lambdaem = 542 nm). In addition, the
      antimicrobial efficiency of Ag-ZnO heterostructured nanorod array shows obvious
      improvement as compared to bare ZnO nanorod array. The cytotoxicity of ZnO
      nanorod array with and without Ag NPs was studied by using 3 T3 mouse fibroblast
      cell line. No significant toxic effect is imposed on the cells. 

PMID- 25852402
TI  - Anisotropic micro-cloths fabricated from DNA-stabilized carbon nanotubes: one
      stop manufacturing with electrode needles.
AB  - Among a variety of solution-based approaches to fabricate anisotropic films of
      aligned carbon nanotubes (CNTs), we focus on the dielectrophoretic assembly
      method using AC electric fields in DNA-stabilized CNT suspensions. We demonstrate
      that a one-stop manufacturing system using electrode needles can draw anisotropic
      DNA-CNT hybrid films of 10 to 100 um in size (i.e., free-standing DNA-CNT micro
      cloths) from the remaining suspension into the atmosphere while maintaining
      structural order. It has been found that a maximal degree of polarization (ca.
      40%) can be achieved by micro-cloths fabricated from a variety of DNA-CNT
      mixtures. Our results suggest that the one-stop method can impart
      biocompatibility to the downsized CNT films and that the DNA-stabilized CNT micro
      cloths directly connected to an electrode could be useful for biofuel cells in
      terms of electron transfer and/or enzymatic activity. 

PMID- 25852403
TI  - Evolution of morphology and microstructure of GaAs/GaSb nanowire
      heterostructures.
AB  - In this paper, we successfully grow GaAs/GaSb core-shell heterostructure
      nanowires (NWs) by molecular beam epitaxy (MBE). The as-grown GaSb shell layer
      forms a wurtzite structure instead of the zinc blende structure that has been
      commonly reported. Meanwhile, a bulgy GaSb nanoplate also appears on top of
      GaAs/GaSb core-shell NWs and possesses a pure zinc blende phase. The growth mode
      for core-shell morphology and underlying mechanism for crystal phase selection of
      GaAs/GaSb nanowire heterostructures are discussed in detail. 

PMID- 25852404
TI  - AlGaN/GaN MISHEMTs with AlN gate dielectric grown by thermal ALD technique.
AB  - Recently, AlN plasma-enhanced atomic layer deposition (ALD) passivation technique
      had been proposed and investigated for suppressing the dynamic on-resistance
      degradation behavior of high-electron-mobility transistors (HEMTs). In this
      paper, a novel gate dielectric and passivation technique for GaN-on-Si AlGaN/GaN
      metal-insulator-semiconductor high-electron-mobility transistors (MISHEMTs) is
      presented. This technique features the AlN thin film grown by thermal ALD at 400
      degrees C without plasma enhancement. A 10.6-nm AlN thin film was grown upon the
      surface of the HEMT serving as the gate dielectric under the gate electrode and
      as the passivation layer in the access region at the same time. The MISHEMTs with
      thermal ALD AlN exhibit enhanced on/off ratio, reduced channel sheet resistance,
      reduction of gate leakage by three orders of magnitude at a bias of 4 V, reduced
      threshold voltage hysteresis of 60 mV, and suppressed current collapse
      degradation. 

PMID- 25852405
TI  - Anatase TiO2 nanotube powder film with high crystallinity for enhanced
      photocatalytic performance.
AB  - We report on the synthesis of TiO2 nanotube (NT) powders using anodic oxidation
      and ultrasonication. Compared to free-standing NT array films, the powder-type
      NTs can be easily fabricated in a cost-effective way. Particularly, without the
      substrate effect arising from underlying Ti metals, highly crystallized NT
      powders with intact tube structures and pure anatase phase can be obtained using
      high-temperature heat treatment. The application of NTs with different
      crystallinity for the photocatalytic decomposition of methylene blue (MB) was
      then demonstrated. The results showed that with increasing annealing temperature,
      the photocatalytic decomposition rate was gradually enhanced, and the NT powder
      electrode annealed at 650 degrees C showed the highest photoactivity. Compared to
      typical NTs annealed at 450 degrees C, the rate constant increased by 2.7-fold,
      although the surface area was 21% lower. These findings indicate that the better
      photocatalytic activity was due to the significantly improved crystallinity of
      anatase anodic NTs in powder form, resulting in a low density of crystalline
      defects. This simple and efficient approach is applicable for scaled-up water
      purification and other light utilization applications. 

PMID- 25852406
TI  - Investigation of GaInAs strain reducing layer combined with InAs quantum dots
      embedded in Ga(In)As subcell of triple junction GaInP/Ga(In)As/Ge solar cell.
AB  - The InAs/GaAs quantum dots structure embedded in GaInP/Ga(In)As/Ge triple
      junction solar cell with and without Ga0.90In0.10As strain reducing layer was
      investigated. Conversion efficiency of 33.91% at 1,000 suns AM 1.5D with
      Ga0.90In0.10As strain reducing layer was demonstrated. A 1.19% improvement of the
      conversion efficiency was obtained via inserting the Ga0.90In0.10As strain
      reducing layer. The main contribution of this improvement was from the increase
      of the short-circuit current, which is caused by the reduction of the Shockley
      Read-Hall recombination centers. Consequently, there was a decrease in open
      circuit voltage due to the lower thermal activation energy of confined carriers
      in Ga0.9In0.1As than GaAs and a reduction in the effective band gap of quantum
      dots. 

PMID- 25852407
TI  - Structure and properties of Co-doped ZnO films prepared by thermal oxidization
      under a high magnetic field.
AB  - The effect of a high magnetic field applied during oxidation on the structure,
      optical transmittance, resistivity, and magnetism of cobalt (Co)-doped zinc oxide
      (ZnO) thin films prepared by oxidizing evaporated Zn/Co bilayer thin films in
      open air was studied. The relationship between the structure and properties of
      films oxidized with and without an applied magnetic field was analyzed. The
      results show that the high magnetic field obviously changed the structure and
      properties of the Co-doped ZnO films. The Lorentz force of the high magnetic
      field suppressed the oxidation growth on nanowhiskers. As a result, ZnO nanowires
      were formed without a magnetic field, whereas polyhedral particles formed under a
      6 T magnetic field. This morphology variation from dendrite to polyhedron caused
      the transmittance below 1,200 nm of the film oxidized under a magnetic field of 6
      T to be much lower than that of the film oxidized without a magnetic field. X-ray
      photoemission spectroscopy indicated that the high magnetic field suppressed Co
      substitution in the ZnO lattice, increased the concentration of oxygen vacancies,
      and changed the chemical state of Co. The increased concentration of oxygen
      vacancies affected the temperature dependence of the resistivity of the film
      oxidized under a magnetic field of 6 T compared with that of the film oxidized
      without a magnetic field. The changes of oxygen vacancy concentration and Co
      state caused by the application of the high magnetic field also increase the
      ferromagnetism of the film at room temperature. All of these results indicate
      that a high magnetic field is an effective tool to modify the structure and
      properties of ZnO thin films. 

PMID- 25852408
TI  - Thermal conductivity enhancement in thermal grease containing different CuO
      structures.
AB  - Different cupric oxide (CuO) structures have attracted intensive interest because
      of their promising applications in various fields. In this study, three kinds of
      CuO structures, namely, CuO microdisks, CuO nanoblocks, and CuO microspheres, are
      synthesized by solution-based synthetic methods. The morphologies and crystal
      structures of these CuO structures are characterized by field-emission scanning
      electron microscope and X-ray diffractometer, respectively. They are used as
      thermal conductive fillers to prepare silicone-based thermal greases, giving rise
      to great enhancement in thermal conductivity. Compared with pure silicone base,
      the thermal conductivities of thermal greases with CuO microdisks, CuO
      nanoblocks, and CuO microspheres are 0.283, 0256, and 0.239 W/mK, respectively,
      at filler loading of 9 vol.%, which increases 139%, 116%, and 99%, respectively.
      These thermal greases present a slight descendent tendency in thermal
      conductivity at elevated temperatures. These experimental data are compared with
      Nan's model prediction, indicating that the shape factor has a great influence on
      thermal conductivity improvement of thermal greases with different CuO
      structures. Meanwhile, due to large aspect ratio of CuO microdisks, they can form
      thermal networks more effectively than the other two structures, resulting in
      higher thermal conductivity enhancement. 

PMID- 25852409
TI  - Structural and optical properties of position-retrievable low-density GaAs
      droplet epitaxial quantum dots for application to single photon sources with
      plasmonic optical coupling.
AB  - The position of a single GaAs quantum dot (QD), which is optically active, grown
      by low-density droplet epitaxy (DE) (approximately 4 QDs/MUm(2)), was directly
      observed on the surface of a 45-nm-thick Al0.3Ga0.7As capping layer. The thin
      thickness of AlGaAs capping layer is useful for single photon sources with
      plasmonic optical coupling. A micro-photoluminescence for GaAs DE QDs has shown
      exciton/biexciton behavior in the range of 1.654 to 1.657 eV. The direct
      observation of positions of low-density GaAs DE QDs would be advantageous for
      mass fabrication of devices that use a single QD, such as single photon sources. 

PMID- 25852410
TI  - A high-performance complementary inverter based on transition metal
      dichalcogenide field-effect transistors.
AB  - For several years, graphene has been the focus of much attention due to its
      peculiar characteristics, and it is now considered to be a representative 2
      dimensional (2D) material. Even though many research groups have studied on the
      graphene, its intrinsic nature of a zero band-gap, limits its use in practical
      applications, particularly in logic circuits. Recently, transition metal
      dichalcogenides (TMDs), which are another type of 2D material, have drawn
      attention due to the advantage of having a sizable band-gap and a high mobility.
      Here, we report on the design of a complementary inverter, one of the most basic
      logic elements, which is based on a MoS2 n-type transistor and a WSe2 p-type
      transistor. The advantages provided by the complementary metal-oxide
      semiconductor (CMOS) configuration and the high-performance TMD channels allow us
      to fabricate a TMD complementary inverter that has a high-gain of 13.7. This work
      demonstrates the operation of the MoS2 n-FET and WSe2 p-FET on the same
      substrate, and the electrical performance of the CMOS inverter, which is based on
      a different driving current, is also measured. 

PMID- 25852411
TI  - Microstructure inhomogeneity of Fe-31%Ni alloy and stabilization of austenite.
AB  - Srystal structure and mechanism of crystallization of Fe-Ni alloys were studied
      by methods of X-ray diffraction and metallography. It has been found that macro-
      and microstructure of austenitic alloy was essentially heterogeneous at the
      contact and free surfaces and in the volume of a ribbon. The indentified
      peculiarities of the austenitic phase in different areas of the ribbon are
      attributed to different cooling rates and the melt crystallization conditions. 

PMID- 25852412
TI  - Enhanced and tunable photoluminescence of polyphenylenevinylenes confined in
      nanocomposite films.
AB  - Conformation of macromolecules and interchain interactions determine spectral
      properties of conjugated polymers (CP). An achievement of spatial confinement of
      isolated chains is one of the routes to use this feature of CP for their
      purposeful usage. In the present work, CP/O300 nanocomposites based on CP -
      poly(p-phenylenevinylene) and poly(2-methoxy-5-(2'-ethylhexyloxy)-1,4
      phenylenevinylene) - and silica nanoparticles (O300) are prepared. In comparison
      with many previously known hybrid nanomaterials synthesized with the similar
      purpose, CP/O300 nanocomposites are characterized by the essentially enhanced and
      tunable photoluminescence. The greatest change of color coordinates is observed
      for poly(p-phenylenevinylene)-based nanocomposites due to specific preparation
      method and interaction with the inorganic component. The main emission from CP in
      the CP/O300 nanocomposites is owing to 0-0 transitions, while 0-1 transitions,
      associated with aggregate states of the CP chains, are suppressed. 

PMID- 25852413
TI  - Preparation of NiO two-dimensional grainy films and their high-performance gas
      sensors for ammonia detection.
AB  - Semiconductor NiO two-dimensional grainy films on glass substrates are shown to
      be an ammonia-sensing devices with excellent comprehensive performance, such as
      the good stability, short response time, outstanding recovery performance,
      excellent sensitivity, and selectivity. The morphology and structure analysis of
      gas sensing materials indicated that the as-fabricated NiO films was uniform and
      highly ordered porous structure on substrates, which composed of small size
      particles with diameters ranging from 8 to 30 nm. The shells of these particles
      were ultrathin amorphous NiO plates, and the core of each particle was face
      centered cubic single crystal structure. In the gas sensing performance tests, we
      found that the excellent electron transport and interconnection properties of
      sensing films improved the stability and recovery performance of sensors, and
      porous surface structure increased the specific surface area of sensing films
      leading to fast response and excellent sensitivity for sensors. Meanwhile, this
      sensors owned outstanding selectivity toward ammonia which could be because NiO
      sensing films had higher binding affinity for the electron-donating ammonia. 

PMID- 25852414
TI  - Primary structure of proteins as a nanowire for metabolic electronic transport.
AB  - It is considered that the major process in an organism is the synthesis of the
      adenosine triphosphate (ATP) molecules (its resumption from the adenosine
      diphosphate (ADP) molecules). These molecules are the basic (if not unique)
      energy resource of an organism. For the completion of process of the ATP
      synthesis in mitochondria, it is necessary to transfer to it a pair of electrons
      from places where electrons rise up as a result of oxidizing processes. Research
      of mechanisms of such transfer is important therefore, in particular, from the
      point of regulative influence on them in medical aims. Various proteins, the
      primary structure of which can provide the transport of electrons between donors
      and acceptors, saturate a volume and membranes of cages. A question about a
      possibility to examine this primary structure of proteins as a nanowire of a
      semiconductor nature is analyzed. The possibility of active transport of
      electrons through its conductivity band is analyzed also. In this paper, it was
      shown that a heterogeneous protein system is possible to be considered as a
      semiconductor with an average-nitrogen nuclear subsystem and with an average
      oxygen electronic subsystem. Also, it was shown that in the potential energy of
      interaction between the electron and the nuclear subsystem indeed exists non
      compensated contributions. These contributions are related to the radicals and
      provide the active transport of electrons along the primary structure of protein
      molecules. It was demonstrated also that external fields can have local
      regulative influence on the transport of electron in proteins by compensating the
      remaining field or strengthening it. Fulfilled analysis gives a possibility in
      zero approximation of the application of representation of numbers of filling to
      the protein molecule, considering it as the nanowire. 

PMID- 25852416
TI  - Nanoprocessing of layered crystalline materials by atomic force microscopy.
AB  - By taking advantage of the mechanical anisotropy of crystalline materials,
      processing at a single-layer level can be realized for layered crystalline
      materials with periodically weak bonds. Mica (muscovite), graphite, molybdenum
      disulfide (MoS2), and boron nitride have layered structures, and there is little
      interaction between the cleavage planes existing in the basal planes of these
      materials. Moreover, it is easy to image the atoms on the basal plane, where the
      processed shape can be observed on the atomic level. This study reviews research
      evaluating the nanometer-scale wear and friction as well as the nanometer-scale
      mechanical processing of muscovite using atomic force microscopy (AFM). It also
      summarizes recent AFM results obtained by our research group regarding the atomic
      scale mechanical processing of layered materials including mica, graphite, MoS2,
      and highly oriented pyrolytic graphite. 

PMID- 25852415
TI  - Synthesis of CuInS2 quantum dots using polyetheramine as solvent.
AB  - This paper presents a facile solvothermal method of synthesizing copper indium
      sulfide (CuInS2) quantum dots (QDs) via a non-coordinated system using
      polyetheramine as a solvent. The structural and optical properties of the
      resulting CuInS2 QDs were investigated using composition analysis, absorption
      spectroscopy, and emission spectroscopy. We employed molar ratios of I, III, and
      VI group elements to control the structure of CuInS2 QDs. An excess of group VI
      elements facilitated precipitation, whereas an excess of group I elements
      resulted in CuInS2 QDs with high photoluminescence quantum yield. The emission
      wavelength and photoluminescence quantum yield could also be modulated by
      controlling the composition ratio of Cu and In in the injection stock solution.
      An increase in the portion of S shifted the emission wavelength of the QDs to a
      shorter wavelength and increased the photoluminescence quantum yield. Our results
      demonstrate that the band gap of the CuInS2 QDs is tunable with size as well as
      the composition of the reactant. The photoluminescence quantum yield of the
      CuInS2 QDs ranged between 0.7% and 8.8% at 250 degrees C. We also determined some
      important physical parameters such as the band gaps and energy levels of this
      system, which are crucial for the application of CuInS2 nanocrystals. 

PMID- 25852417
TI  - Intriguing photo-control of exchange bias in BiFeO3/La2/3Sr1/3MnO3 thin films on
      SrTiO3 substrates.
AB  - To date, electric fields have been widely used to control the magnetic properties
      of BiFeO3-based antiferromagnet/ferromagnet heterostructures through application
      of an exchange bias. To extend the applicability of exchange bias, however, an
      alternative mechanism to electric fields is required. Here, we report the photo
      control of exchange bias in BiFeO3/La2/3Sr1/3MnO3 thin films on an SrTiO3
      substrate. Through an ex situ pulsed laser deposition technique, we successfully
      synthesized epitaxial BiFeO3/La2/3Sr1/3MnO3 thin films on SrTiO3 substrates. By
      measuring magnetoresistance under light illumination, we investigated the effect
      of light illumination on resistance, exchange bias, and coercive field in
      BiFeO3/La2/3Sr1/3MnO3 thin films. After illumination of red and blue lights, the
      exchange bias was sharply reduced compared to that measured in the dark. With
      increasing light intensity, the exchange bias under red and blue lights initially
      decreased to zero and then appeared again. It is possible to reasonably explain
      these behaviors by considering photo-injection from SrTiO3 and the photo
      conductivity of La2/3Sr1/3MnO3. This study may provide a fundamental
      understanding of the mechanism underlying photo-controlled exchange bias, which
      is significant for the development of new functional spintronic devices. 

PMID- 25852418
TI  - First-principles calculations of perpendicular magnetic anisotropy in Fe1-x Co x
      /MgO(001) thin films.
AB  - The perpendicular magnetic anisotropy (PMA) of Fe1-x Co x thin films on MgO(001)
      was investigated via first-principles density-functional calculations. Four
      different configurations were considered based on their ground states: Fe/MgO,
      Fe12Co4/MgO, Fe10Co6/MgO, and Fe8Co8/MgO. As the Co composition increases, the
      amplitude of PMA increases first from Fe/MgO to Fe12Co4/MgO, and then decreases
      in Fe10Co6/MgO; finally, the magnetic anisotropy becomes horizontal in
      Fe8Co8/MgO. Analysis based on the second-order perturbation of the spin-orbit
      interaction was carried out to illustrate the contributions from Fe and Co atoms
      to PMA, and the differential charge density was calculated to give an intuitive
      comparison of 3d orbital occupancy. The enhanced PMA in Fe12Co4/MgO is ascribed
      to the optimized combination of occupied and unoccupied 3d states around the
      Fermi energy from both interface Fe and Co atoms, while the weaker PMA in
      Fe10Co6/MgO is mainly attributed to the modulation of the interface Co-d xy
      orbital around the Fermi energy. By adjusting the Co composition in Fe1-x Co x ,
      the density of states of transitional metal atoms will be modulated to optimize
      PMA for future high-density memory application. 

PMID- 25852419
TI  - Direct patterning of gold nanoparticles using flexographic printing for
      biosensing applications.
AB  - In this paper, we have presented the use of flexographic printing techniques in
      the selective patterning of gold nanoparticles (AuNPs) onto a substrate. Highly
      uniform coverage of AuNPs was selectively patterned on the substrate surface,
      which was subsequently used in the development of a glucose sensor. These AuNPs
      provide a biocompatible site for the attachment of enzymes and offer high
      sensitivity in the detection of glucose due to their large surface to volume
      ratio. The average size of the printed AuNPs is less than 60 nm. Glucose sensing
      tests were performed using printed carbon-AuNP electrodes functionalized with
      glucose oxidase (GOx). The results showed a high sensitivity of 5.52 MUA mM(-1)
      cm(-2) with a detection limit of 26 MUM. We have demonstrated the fabrication of
      AuNP-based biosensors using flexographic printing, which is ideal for low-cost,
      high-volume production of the devices. 

PMID- 25852420
TI  - Uniformity and passivation research of Al2O3 film on silicon substrate prepared
      by plasma-enhanced atom layer deposition.
AB  - Plasma-enhanced atom layer deposition (PEALD) can deposit denser films than those
      prepared by thermal ALD. But the improvement on thickness uniformity and the
      decrease of defect density of the films deposited by PEALD need further research.
      A PEALD process from trimethyl-aluminum (TMA) and oxygen plasma was investigated
      to study the influence of the conditions with different plasma powers and
      deposition temperatures on uniformity and growth rate. The thickness and
      refractive index of films were measured by ellipsometry, and the passivation
      effect of alumina on n-type silicon before and after annealing was measured by
      microwave photoconductivity decay method. Also, the effects of deposition
      temperature and annealing temperature on effective minority carrier lifetime were
      investigated. Capacitance-voltage and conductance-voltage measurements were used
      to investigate the interface defect density of state (D it) of Al2O3/Si. Finally,
      Al diffusion P(+) emitter on n-type silicon was passivated by PEALD Al2O3 films.
      The conclusion is that the condition of lower substrate temperature accelerates
      the growth of films and that the condition of lower plasma power controls the
      films' uniformity. The annealing temperature is higher for samples prepared at
      lower substrate temperature in order to get the better surface passivation
      effects. Heavier doping concentration of Al increased passivation quality after
      annealing by the effective minority carrier lifetime up to 100 MUs. 

PMID- 25852421
TI  - A flexible transparent gas barrier film employing the method of mixing ALD/MLD
      grown Al2O3 and alucone layers.
AB  - Atomic layer deposition (ALD) has been widely reported as a novel method for thin
      film encapsulation (TFE) of organic light-emitting diodes and organic
      photovoltaic cells. Both organic and inorganic thin films can be deposited by ALD
      with a variety of precursors. In this work, the performances of Al2O3 thin films
      and Al2O3/alucone hybrid films have been investigated. The samples with a 50 nm
      Al2O3 inorganic layer deposited by ALD at a low temperature of 80 degrees C
      showed higher surface roughness (0.503 +/- 0.011 nm), higher water vapor
      transmission rate (WVTR) values (3.77 * 10(-4) g/m(2)/day), and lower
      transmittance values (61%) when compared with the Al2O3 (inorganic)/alucone
      (organic) hybrid structure under same conditions. Furthermore, a bending test
      upon single Al2O3 layers showed an increased WVTR of 1.59 * 10(-3) g/m(2)/day.
      However, the film with a 4 nm alucone organic layer inserted into the center
      displayed improved surface roughness, barrier performance, and transmittance.
      After the bending test, the hybrid film with 4 nm equally distributed alucone
      maintained better surface roughness (0.339 +/- 0.014 nm) and barrier properties
      (9.94 * 10(-5) g/m(2)/day). This interesting phenomenon reveals that multilayer
      thin films consisting of inorganic layers and decentralized alucone organic
      components have the potential to be useful in TFE applications on flexible
      optical electronics. 

PMID- 25852422
TI  - A novel method to fabricate CoFe2O4/SrFe12O19 composite ferrite nanofibers with
      enhanced exchange coupling effect.
AB  - Nanocomposite of CoFe2O4/SrFe12O19 has been synthesized by the electrospinning
      and calcination process. A novel method that cobalt powder was used to replace
      traditional cobalt salt in the precursor sol-gel for electrospinning was
      proposed. The crystal structures, morphologies, and magnetic properties of these
      samples have been characterized in detail. Moreover, when the average crystallite
      size of the hard/soft phases reached up to an optimal value, the CoFe2O4 have an
      enhanced saturation magnetization of 62.8 emu/g and a coercivity of 2,290 Oe.
      Significantly, the hysteresis loops for the nanocomposites show a single-phase
      magnetization behavior, and it has been found that the exchange coupling
      interaction strongly exists in the CoFe2O4/SrFe12O19 magnetic nanocomposite
      nanofibers. 

PMID- 25852423
TI  - Hydrothermal-assisted exfoliation of Y/Tb/Eu ternary layered rare-earth
      hydroxides into tens of micron-sized unilamellar nanosheets for highly oriented
      and color-tunable nano-phosphor films.
AB  - Efficient exfoliation of well-crystallized (Y0.96Tb x Eu0.04-x )2(OH)5NO3 . nH2O
      (0 <= x <= 0.04) layered rare-earth hydroxide (LRH) crystals into tens of micron
      sized unilamellar nanosheets has been successfully achieved by inserting water
      insoluble oleate anions (C17H33COO(-)) into the interlayer of the LRH via
      hydrothermal anion exchange at 120 degrees C, followed by delaminating in
      toluene. The intercalation of oleate anions led to extremely expanded interlayer
      distances (up to approximately 5.2 nm) of the LRH crystals and accordingly
      disordered stacking of the ab planes along the c-axis and also weakened
      interlayer interactions, without significantly damaging the ab plane. As a
      consequence, the thickness of the LRH crystals increased from approximately 1 to
      10 MUm, exhibiting a behavior similar to that observed from the smectite clay in
      water. Highly [111]-oriented and approximately 100-nm thick oxide films of
      (Y0.96Tb x Eu0.04-x ) 2O3 (0 <= x <= 0.04) have been obtained through spin
      coating of the exfoliated colloidal nanosheets on quartz substrate, followed by
      annealing at 800 degrees C. Upon UV excitation at 266 nm, the oxide transparent
      films exhibit bright luminescence, with the color-tunable emission from red to
      orange, yellow, and then green by increasing the Tb(3+) content from x = 0 to
      0.04. 

PMID- 25852424
TI  - The synthesis of controlled shape nanoplasmonic silver-silica structures by
      combining sol-gel technique and direct silver reduction.
AB  - In this work, we have obtained nanoplasmonic silver structures deposited on the
      glass substrates by combining sol-gel technology and direct silver ion reduction
      on the film surfaces. The key point of the work was the usage of polyethylene
      glycol 400 (PEG 400) both as the pore former and reducing agent for silver ions.
      We have investigated the influence of PEG 400 amount on the formation of silver
      nanoparticles on the film surface. It was found that control of PEG 400 amount in
      the sols allows the creation of porous films with specific organized silver
      nanoparticles or clusters on the surface. Optical, morphological and structural
      characteristics of the structures were measured and studied. Atomic force
      microscopy (AFM) and scanning electron microscopy (SEM) were used for
      nanostructure size and shape characterization. We were able to form a 40- to 200
      nm-diameter ring-type, spherical and self-assembled nanoparticles on the film
      surface. The results of UV-vis absorbance spectra have shown the high quality of
      plasmonic structures with plasmon resonance wavelength in the region between 470
      and 480 nm. The synthesized silica films decorated with silver nanoparticles were
      tested as substrates for the surface-enhanced Raman spectroscopy (SERS) and
      showed an enhancement relative to micro-Raman of more than 200 times. 

PMID- 25852425
TI  - Protamine nanoparticles for improving shRNA-mediated anti-cancer effects.
AB  - Protamine nanoparticles were designed by encapsulating small hairpin RNA (shRNA)
      expressing plasmid DNA targeting the Bcl-2 gene (shBcl-2) to silence apoptosis
      related Bcl-2 protein for improving the transfection efficiency and cytotoxicity
      in cancer therapy. Our findings demonstrated that the obtained protamine
      nanoparticles possessed excellent characterizations of small particle size,
      homogenous distribution, positive charge, and high encapsulation efficiency of
      gene. shBcl-2 loaded in nanoparticles (NPs) was protected effectively from the
      degradation of DNase I and serum. More importantly, it significantly improved the
      efficiency of transfection of shRNA in vitro in A549 cells and increased its
      cytotoxicity and induced more cell apoptosis by silencing Bcl-2. 

PMID- 25852426
TI  - Excellent resistive switching properties of atomic layer-deposited
      Al2O3/HfO2/Al2O3 trilayer structures for non-volatile memory applications.
AB  - We have demonstrated a flexible resistive random access memory unit with trilayer
      structure by atomic layer deposition (ALD). The device unit is composed of
      Al2O3/HfO2/Al2O3-based functional stacks on TiN-coated Si substrate. The cross
      sectional HRTEM image and XPS depth profile of Al2O3/HfO2/Al2O3 on TiN-coated Si
      confirm the existence of interfacial layers between trilayer structures of
      Al2O3/HfO2/Al2O3 after 600 degrees C post-annealing. The memory units of
      Pt/Al2O3/HfO2/Al2O3/TiN/Si exhibit a typical bipolar, reliable, and reproducible
      resistive switching behavior, such as stable resistance ratio (>10) of OFF/ON
      states, sharp distribution of set and reset voltages, better switching endurance
      up to 10(3) cycles, and longer data retention at 85 degrees C over 10 years. The
      possible switching mechanism of trilayer structure of Al2O3/HfO2/Al2O3 has been
      proposed. The trilayer structure device units of Al2O3/HfO2/Al2O3 on TiN-coated
      Si prepared by ALD may be a potential candidate for oxide-based resistive random
      access memory. 

PMID- 25852427
TI  - Soft magnetic properties of nanocrystalline Fe73B7Si16Nb3Cu1 alloy after rapid
      heating under tensile stress.
AB  - Amorphous Fe73B7Si16Nb3Cu1 ribbon was crystallized rapidly by electric current
      heating under simultaneously applied tensile stress along the ribbon axis. As a
      result, strong transverse magnetic anisotropy was induced in the ribbon. Dynamic
      magnetic properties of the ribbons rapidly heated either under the tensile stress
      or without tensile stress were measured using toroidal cores. Optimal electric
      current heating regime that provides maximum improvement of the initial magnetic
      permeability and core loss was determined. Tensile stress increase from 0 to 180
      MPa was shown to result in the decrease of the initial magnetic permeability down
      to 400 and core loss at frequencies from 0.4 to 200 kHz. Comparative analysis of
      magnetic properties of the cut core (with non-magnetic gap) and the cores heated
      under tensile stress was carried out. The magnetic properties of the latter cores
      are advantageous for manufacturing the reactors and linear chokes of switch-mode
      power supplies. 

PMID- 25852428
TI  - Oxidation precursor dependence of atomic layer deposited Al2O3 films in a
      Si:H(i)/Al2O3 surface passivation stacks.
AB  - In order to obtain a good passivation of a silicon surface, more and more stack
      passivation schemes have been used in high-efficiency silicon solar cell
      fabrication. In this work, we prepared a-Si:H(i)/Al2O3 stacks on KOH solution
      polished n-type solar grade mono-silicon(100) wafers. For the Al2O3 film
      deposition, both thermal atomic layer deposition (T-ALD) and plasma enhanced
      atomic layer deposition (PE-ALD) were used. Interface trap density spectra were
      obtained for Si passivation with a-Si films and a-Si:H(i)/Al2O3 stacks by a non
      contact corona C-V technique. After the fabrication of a-Si:H(i)/Al2O3 stacks,
      the minimum interface trap density was reduced from original 3 * 10(12) to 1 *
      10(12) cm(-2) eV(-1), the surface total charge density increased by nearly one
      order of magnitude for PE-ALD samples and about 0.4 * 10(12) cm(-2) for a T-ALD
      sample, and the carrier lifetimes increased by a factor of three (from about 10
      MUs to about 30 MUs). Combining these results with an X-ray photoelectron
      spectroscopy analysis, we discussed the influence of an oxidation precursor for
      ALD Al2O3 deposition on Al2O3 single layers and a-Si:H(i)/Al2O3 stack surface
      passivation from field-effect passivation and chemical passivation perspectives.
      In addition, the influence of the stack fabrication process on the a-Si film
      structure was also discussed in this study. 

PMID- 25852429
TI  - Spray cooling characteristics of nanofluids for electronic power devices.
AB  - The performance of a single spray for electronic power devices using deionized
      (DI) water and pure silver (Ag) particles as well as multi-walled carbon nanotube
      (MCNT) particles, respectively, is studied herein. The tests are performed with a
      flat horizontal heated surface using a nozzle diameter of 0.5 mm with a definite
      nozzle-to-target surface distance of 25 mm. The effects of nanoparticle volume
      fraction and mass flow rate of the liquid on the surface heat flux, including
      critical heat flux (CHF), are explored. Both steady state and transient data are
      collected for the two-phase heat transfer coefficient, boiling curve/ cooling
      history, and the corresponding CHF. The heat transfer removal rate can reach up
      to 274 W/cm(2) with the corresponding CHF enhancement ratio of 2.4 for the
      Ag/water nanofluids present at a volume fraction of 0.0075% with a low mass flux
      of 11.9 * 10(-4) kg/cm(2)s. 

PMID- 25852430
TI  - Nanosized silver (II) pyridoxine complex to cause greater inflammatory response
      and less cytotoxicity to RAW264.7 macrophage cells.
AB  - With advancements in nanotechnology, silver has been engineered into a nanometre
      size and has attracted great research interest for use in the treatment of
      wounds. Silver nanoparticles (AgNPs) have emerged as a potential alternative to
      conventional antibiotics because of their potential antimicrobial property.
      However, AgNPs also induce cytotoxicity, generate reactive oxygen species (ROS),
      and cause mitochondrial damage to human cells. Pyridoxine possesses antioxidant
      and cell proliferation activity. Therefore, in the present investigation, a
      nanosilver-pyridoxine complex (AgPyNP) was synthesized, and its cytotoxicity and
      immune response was compared with AgNPs in macrophage RAW264.7 cells. Results
      revealed that AgPyNPs showed less cytotoxicity compared with AgNPs by producing a
      smaller amount of ROS in RAW264.7 cells. Surprisingly, however, AgPyNPs caused
      macrophage RAW264.7 cells to secrete a larger amount of interleukin-8 (IL-8) and
      generate a more active inflammatory response compared to AgNPs. It activated TNF
      alpha, NF-kappaB p65, and NF-kappaB p50 to generate a more vigorous immune
      protection that produces a greater amount of IL-8 compared to AgNPs. Overall
      findings indicate that AgPyNPs exhibited less cytotoxicity and evoked a greater
      immune response in macrophage RAW264.7 cells. Thus, it can be used as a better
      wound-healing agent than AgNPs. Graphical AbstractFigurative representation of
      the comparison of AgNPs and AgPyNPs in macrophage RAW264.7 cells in terms of
      cytotoxicity and immune response. 

PMID- 25852431
TI  - Numerical study of natural convection in a horizontal cylinder filled with water
      based alumina nanofluid.
AB  - Natural heat convection of water-based alumina (Al2O3/water) nanofluids (with
      volume fraction 1% and 4%) in a horizontal cylinder is numerically investigated.
      The whole three-dimensional computational fluid dynamics (CFD) procedure is
      performed in a completely open-source way. Blender, enGrid, OpenFOAM and ParaView
      are employed for geometry creation, mesh generation, case simulation and post
      process, respectively. Original solver 'buoyantBoussinesqSimpleFoam' is selected
      for the present study, and a temperature-dependent solver
      'buoyantBoussinesqSimpleTDFoam' is developed to ensure the simulation is more
      realistic. The two solvers are used for same cases and compared to corresponding
      experimental results. The flow regime in these cases is laminar (Reynolds number
      is 150) and the Rayleigh number range is 0.7 * 10(7) ~ 5 * 10(7). By comparison,
      the average natural Nusselt numbers of water and Al2O3/water nanofluids are found
      to increase with the Rayleigh number. At the same Rayleigh number, the Nusselt
      number is found to decrease with nanofluid volume fraction. The temperature
      dependent solver is found better for water and 1% Al2O3/water nanofluid cases,
      while the original solver is better for 4% Al2O3/water nanofluid cases.
      Furthermore, due to strong three-dimensional flow features in the horizontal
      cylinder, three-dimensional CFD simulation is recommended instead of two
      dimensional simplifications. 

PMID- 25852432
TI  - Nucleation mechanism of nano-sized NaZn13-type and alpha-(Fe,Si) phases in La-Fe
      Si alloys during rapid solidification.
AB  - The nucleation mechanism involving rapid solidification of undercooled La-Fe-Si
      melts has been studied experimentally and theoretically. The classical nucleation
      theory-based simulations show a competitive nucleation process between the alpha
      (Fe,Si) phase (size approximately 10 to 30 nm) and the cubic NaZn13-type phase
      (hereinafter 1:13 phase, size approximately 200 to 400 nm) during rapid
      solidification, and that the undercooled temperature change ?T plays an important
      factor in this process. The simulated results about the nucleation rates of the
      alpha-(Fe,Si) and 1:13 phases in La-Fe-Si ribbons fabricated by a melt-spinner
      using a copper wheel with a surface speed of 35 m/s agree well with the XRD, SEM,
      and TEM studies of the phase structure and microstructure of the ribbons. Our
      study paves the way for designing novel La-Fe-Si materials for a wide range of
      technological applications. 

PMID- 25852433
TI  - A facile hydrothermal approach to the synthesis of nanoscale rare earth
      hydroxides.
AB  - Nanosized rare earth (RE) hydroxides including La(OH)3, Nd(OH)3, Pr(OH)3,
      Sm(OH)3, Gd(OH)3, and Er(OH)3 with rod-like morphology are fabricated via a
      convenient hydrothermal approach. This strategy calls for the first preparation
      of metal complexes between RE precursors and dodecylamine (DDA) in water/ethanol
      mixture at room temperature and subsequent thermal decomposition at elevated
      temperature. The influence of reaction time and water/ethanol volume ratios on
      the morphology and size of as-prepared RE hydroxides are investigated. CeO2
      nanoparticles with spherical shape could be directly obtained by hydrothermal
      treatment of complexes formed between Ce precursors and DDA. In addition, by
      further calcinating the RE hydroxides at high temperature in air, RE oxide
      nanorods could be readily produced. 

PMID- 25852434
TI  - Bright, stable, and water-soluble CuInS2/ZnS nanocrystals passivated by
      cetyltrimethylammonium bromide.
AB  - We report a highly bright and stable aqueous dispersion of CuInS2/ZnS (CIS/ZnS)
      nanocrystals (NCs) using surfactant-assisted microemulsion and cold treatment.
      CIS/ZnS NCs were facilely synthesized via a stepwise, consecutive hybrid flow
      reactor approach. To stabilize the optical properties of hydrophobic CIS/ZnS NCs,
      cetyltrimethylammonium bromide (CTAB) was chosen as a matrix for aqueous phase
      transfer. As the result, a high quantum yield (QY) of 56.0% and excellent
      photostability were acquired in aqueous media. For removing excessive
      surfactants, cold treatment (4 degrees C) of the CTAB-water solution was adopted
      to prevent further agglomeration of CIS/ZnS NCs, which could secure high
      stability over 6 months (less 2% reduction in QY). The optical features and
      structure of the obtained CTAB stabilized CIS/ZnS (CTAB-CIS/ZnS) NCs have been
      characterized by UV-vis and photoluminescence (PL) spectroscopies, XRD, XPS, EDX,
      and TEM. The high stability and PL of water soluble CTAB-CIS/ZnS NCs suggest
      their potential in nanoelectronics and bioapplications. 

PMID- 25852435
TI  - Quantum dot-sensitized solar cells having 3D-TiO2 flower-like structures on the
      surface of titania nanorods with CuS counter electrode.
AB  - The photovoltaic performance of a quantum dot (QD)-sensitized solar cell
      consisting of CdS/CdSe/ZnS QDs loaded onto the surface of the three-dimensional
      (3D) flower-like TiO2 structure grown on an array (1D) of TiO2 nanorods (FTiR) is
      studied. The flower-like structure on the rod-shaped titania was synthesized
      using a double-step hydrothermal process. The FTiR array exhibited a 3D/1D
      composite structure with a specific surface area of 81.87 m(2)/g. Using CuS as
      the counter electrode instead of Pt offers the best performance and leads to an
      increase in the conversion efficiency (eta). The efficiency of the CdS/CdSe/ZnS
      QD-loaded FTiR assembling CuS counter electrode cell improved from eta = 2.715%
      (Voc = 0.692 V, Jsc = 5.896 mA/cm(2), FF = 0.665) to eta = 0.703% (Voc = 0.665 V,
      Jsc = 2.108 mA/cm(2), FF = 0.501) for the QD-loaded FTiR assembling Pt counter
      electrode cell. These studies reveal a synergistically beneficial effect on the
      solar-to-current conversion of these QD-sensitized solar cells when a CuS counter
      electrode is used instead of the usual Pt counter electrode. 

PMID- 25852436
TI  - Biosynthesis of gold nanoparticles assisted by the intracellular protein extract
      of Pycnoporus sanguineus and its catalysis in degradation of 4-nitroaniline.
AB  - The development of green procedure for the synthesis of gold nanoparticles
      (AuNPs) has gained great interest in the field of nanotechnology. Biological
      synthetic routes are considered to be environmentally benign and cost-effective.
      In the present study, the feasibility of AuNPs' synthesis via intracellular
      protein extract (IPE) of Pycnoporus sanguineus was explored. The characteristics
      of generated particles of formation, crystalline nature, and morphology and
      dimension were analyzed by UV-vis spectroscopy, X-ray diffraction (XRD) and
      transmission electron microscopy (TEM), respectively. UV-vis spectra exhibited
      strong absorption peaks in 520 to 560 nm, indicating the formation of AuNPs. XRD
      analysis revealed that the formed AuNPs were purely crystalline in nature. TEM
      observation showed that AuNPs with various shapes including spherical, pseudo
      spherical, triangular, truncated triangular, pentagonal, and hexagonal, ranging
      from several to several hundred nanometers, were synthesized under different
      conditions. The average size of AuNPs decreased from 61.47 to 29.30 nm as the IPE
      addition increased from 10 to 80 mL. When the initial gold ion concentration
      changed from 0.5 to 2.0 mM, the average size rose from 25.88 to 51.99 nm. As in
      the case of solution pH, the average size was 84.29 nm with solution pH of 2.0,
      which diminished to 6.07 nm with solution pH of 12.0. Fourier transform infrared
      (FTIR) analysis implied that the functional groups including hydroxyl, amine, and
      carboxyl were involved in the reduction of gold ions and stabilization of AuNPs.
      The catalysis results showed that 0.019 mg of AuNPs with average size of 6.07 nm
      could catalyze the complete degradation of 12.5 MUmol of 4-nitroaniline within 6
      min and the degradation rate increased drastically with the addition of AuNPs.
      All the results suggested that the IPE of P. sanguineus could be potentially
      applied for the eco-friendly synthesis of AuNPs. 

PMID- 25852437
TI  - Preparation of PEDOT/GO, PEDOT/MnO2, and PEDOT/GO/MnO2 nanocomposites and their
      application in catalytic degradation of methylene blue.
AB  - The nanocomposite materials of poly(3,4-ethylenedioxythiophene)/graphene oxide
      (PEDOT/GO), poly(3,4-ethylenedioxythiophene)/MnO2 (PEDOT/MnO2), and poly(3, 4
      ethylenedioxythiophene)/graphene oxide/MnO2 (PEDOT/GO/MnO2) were successfully
      prepared by facile and template-free solution method. The structure and
      morphology of nanonanocomposites were characterized by Fourier transform infrared
      spectroscopy (FTIR), ultraviolet-visible absorption spectra (UV-vis), field
      emission scanning electron microscope (FESEM), X-ray diffraction (XRD), and
      energy-dispersive X-ray spectroscopy (EDX), respectively. The catalytic
      activities of nanocomposites were investigated through the degradation processes
      of methylene blue (MB) solution under dark, UV light, and nature sunlight
      irradiation, respectively. The results displayed that nanocomposites were
      successfully synthesized, and PEDOT/GO had higher conjugation length and doped
      degree than pure PEDOT. However, the introduction of MnO2 could lead to the
      reduction of conjugation length and doped degree in PEDOT/MnO2 and PEDOT/GO/MnO2
      nanocomposites. The field emission scanning electron microscope (FESEM) analysis
      also showed that both MnO2 and GO had some effect on the morphology of
      nanocomposites. The catalytic activities of pure PEDOT and nanocomposites were in
      the order of PEDOT/GO/MnO2 > PEDOT/MnO2 > PEDOT/GO > pure PEDOT. Besides, the
      catalytic results also showed that the highest degradation efficiency of MB after
      7 h occurred in the PEDOT/GO/MnO2 composite in three irradiation. 

PMID- 25852438
TI  - Effect of single-walled carbon nanotubes on tumor cells viability and formation
      of multicellular tumor spheroids.
AB  - ABSTRACT: This paper describes the impact of different concentrations of single
      walled carbon nanotubes (SWCNTs) on cell viability of breast adenocarcinoma, MCF
      7 line, and formation of multicellular tumor spheroids (MTS). Chemical
      composition and purity of nanotubes is controlled by Fourier transform infrared
      spectroscopy. The strength and direction of the influence of SWCNTs on the tumor
      cell population was assessed by cell counting and measurement of the volume of
      multicellular tumor spheroids. Effect of SWCNTs on the formation of multicellular
      spheroids was compared with the results obtained by culturing tumor cells with
      ultra dispersed diamonds (UDDs). Our results demonstrated that SWCNTs at
      concentrations ranging from 12.5 to 50 MUg/ml did not have cytotoxic influence on
      tumor cells; instead, they had weak cytostatic effect. The increasing of SWCNTs
      concentration to 100 to 200 MUg/ml stimulated proliferation of tumor cells,
      especially in suspension fractions. The result of this influence was in formation
      of more MTS in cell culture with SWCNTs compared with UDDs and control samples.
      In result, the median volume of MTS after cultivation with SWCNTs at 100 to 200
      MUg/ml concentrations is 3 to 5 times greater than that in samples which were
      incubated with the UDDs and is 2.5 times greater than that in control cultures.
      So, if SWCNTs reduced cell adhesion to substrate and stimulated formation of
      tumor cell aggregates volume near 7 . 10(-3) mm(3), at the same time, UDDs
      reduced adhesion and cohesive ability of cells and stimulated generation of cell
      spheroids volume no more than 4 . 10(-3) mm(3). Our results could be useful for
      the control of cell growth in three-dimensional culture. PACS: 61. 46 + w; 61.48
      + c; 61.48De; 87.15-v; 87.64-t.

PMID- 25852439
TI  - Random nanostructured metallic films for environmental monitoring and optical
      sensing: experimental and computational studies.
AB  - Nanostructured silver films are studied using computational and experimental
      methods. Surface plasmon resonance-related phenomena are emphasized. Resonant
      optical absorption band changes due to the influence of noxious gases are
      investigated. Amplification of light at the film surface due to local
      electromagnetic field enhancement at the nanoscale is discussed based on finite
      difference time domain calculations. 

PMID- 25852440
TI  - Structural transformations in austenitic stainless steel induced by deuterium
      implantation: irradiation at 100 K.
AB  - Deuterium thermal desorption spectra were investigated on the samples of
      austenitic stainless steel 18Cr10NiTi preimplanted at 100 K with deuterium ions
      in the dose range from 3 * 10(15) to 5 * 10(18) D/cm(2). The kinetics of
      structural transformation development in the implantation steel layer was traced
      from deuterium thermodesorption spectra as a function of implanted deuterium
      concentration. At saturation of austenitic stainless steel 18Cr10NiTi with
      deuterium by means of ion implantation, structural-phase changes take place,
      depending on the dose of implanted deuterium. The maximum attainable
      concentration of deuterium in steel is C = 1 (at.D/at.met. = 1/1). The increase
      in the implanted dose of deuterium is accompanied by the increase in the retained
      deuterium content, and as soon as the deuterium concentration attains C ~ 0.5 the
      process of shear martensitic structural transformation in steel takes place. It
      includes the formation of bands, body-centered cubic (bcc) crystal structure, and
      the ferromagnetic phase. Upon reaching the deuterium concentration C > 0.5, the
      presence of these molecules causes shear martensitic structural transformations
      in the steel, which include the formation of characteristic bands, bcc crystal
      structure, and the ferromagnetic phase. At C >= 0.5, two hydride phases are
      formed in the steel, the decay temperatures of which are 240 and 275 K. The
      hydride phases are formed in the bcc structure resulting from the martensitic
      structural transformation in steel. 

PMID- 25852441
TI  - SHANK Mutations May Disorder Brain Development.

PMID- 25852442
TI  - Genomic sequencing and the impact of molecular diagnosis on patient care.
AB  - Evolving sequencing technologies allow more accurate, efficient and affordable
      genomic analysis. As a result, these technologies are increasingly available,
      especially to provide molecular diagnoses for patients with suspected genetic
      disorders. However, there are many challenges to using genomic sequencing to
      benefit patients, including concerns that there is insufficient evidence that
      identifying an underlying molecular explanation may positively impact a patient's
      healthcare. This concern has many repercussions, including funding and/or (in
      some countries and healthcare systems) insurance reimbursement for genomic
      sequencing. To investigate this concern, all monogenic disorders were analyzed
      based on the impact of achieving molecular diagnosis. Of the 2,849 individual
      genes in which germline mutations cause disorders (not including contiguous gene
      syndromes or what may be categorized as susceptibility alleles), our analyses
      showed a specific, available intervention related to at least one affected organ
      system for 1,419 (49.8%) genes. In 95.6% of these genes, the intervention(s)
      would be recommended during the pediatric time frame. 

PMID- 25852444
TI  - Whole-Exome Sequencing in the Clinic: Lessons from Six Consecutive Cases from the
      Clinician's Perspective.
AB  - Whole-exome sequencing (WES) is being used clinically to diagnose rare Mendelian
      disorders, especially when standard tests have failed. The diagnostic yield from
      WES is reported to be ~15-30%; however, data regarding the clinical utility and
      interpretative challenges from the clinician's perspective are lacking. Here, we
      present a series of the first 6 unselected consecutive cases seen over a period
      of 6 months where WES was employed in clinical labs via trio-based testing
      (proband and parents). While we do not discount the value of WES in the clinical
      setting, our cases and experience illustrate the significant clinical challenges
      of WES, even when a diagnosis may be achieved. 

PMID- 25852443
TI  - Connecting the CNTNAP2 Networks with Neurodevelopmental Disorders.
AB  - Based on genomic rearrangements and copy number variations, the contactin
      associated protein-like 2 gene (CNTNAP2) has been implicated in
      neurodevelopmental disorders such as Gilles de la Tourette syndrome, intellectual
      disability, obsessive compulsive disorder, cortical dysplasia-focal epilepsy
      syndrome, autism, schizophrenia, Pitt-Hopkins syndrome, and attention deficit
      hyperactivity disorder. To explain the phenotypic pleiotropy of CNTNAP2
      alterations, several hypotheses have been put forward. Those include gene
      disruption, loss of a gene copy by a heterozygous deletion, altered regulation of
      gene expression due to loss of transcription factor binding and DNA methylation
      sites, and mutations in the amino acid sequence of the encoded protein which may
      provoke altered interactions of the CNTNAP2-encoded protein, Caspr2, with other
      proteins. Also exome sequencing, which covers <0.2% of the CNTNAP2 genomic DNA,
      has revealed numerous single nucleotide variants in healthy individuals and in
      patients with neurodevelopmental disorders. In some of these disorders,
      disruption of CNTNAP2 may be interpreted as a susceptibility factor rather than a
      directly causative mutation. In addition to being associated with impaired
      development of language, CNTNAP2 may turn out to be a central node in the
      molecular networks controlling neurodevelopment. This review discusses the impact
      of CNTNAP2 mutations on its functioning at multiple levels of the combinatorial
      genetic networks that govern brain development. In addition, recommendations for
      genomic testing in the context of clinical genetic management of patients with
      neurodevelopmental disorders and their families are put forward. 

PMID- 25852446
TI  - Cleft lip/palate, short stature, and developmental delay in a boy with a 5.6-mb
      interstitial deletion involving 10p15.3p14.
AB  - The chromosome interval 10p15.3p14 harbors about a dozen genes. This region has
      been implicated in a few well-known human phenotypes, namely HDR syndrome
      (hypoparathyroidism, sensorineural deafness, and renal dysplasia) and DGS2
      (DiGeorge syndrome 2), but a number of variable phenotypes have also been
      reported. Cleft lip/palate seems to be a very unusual finding within the clinical
      spectrum of patients with this deletion. Here, we report a male child born with
      short stature, cleft lip/palate, and feeding problems who was found to have a 5.6
      Mb deletion at 10p15.3p14. 

PMID- 25852447
TI  - A novel mutation in the endothelin B receptor gene in a moroccan family with shah
      waardenburg syndrome.
AB  - Waardenburg syndrome (WS) is a neurocristopathy disorder combining sensorineural
      deafness and pigmentary abnormalities. The presence of additional signs defines
      the 4 subtypes. WS type IV, also called Shah-Waardenburg syndrome (SWS), is
      characterized by the association with congenital aganglionic megacolon
      (Hirschsprung disease). To date, 3 causative genes have been related to this
      congenital disorder. Mutations in the EDNRB and EDN3 genes are responsible for
      the autosomal recessive form of SWS, whereas SOX10 mutations are inherited in an
      autosomal dominant manner. We report here the case of a 3-month-old Morrocan girl
      with WS type IV, born to consanguineous parents. The patient had 3 cousins who
      died in infancy with the same symptoms. Molecular analysis by Sanger sequencing
      revealed the presence of a novel homozygous missense mutation c.1133A>G
      (p.Asn378Ser) in the EDNRB gene. The proband's parents as well as the parents of
      the deceased cousins are heterozygous carriers of this likely pathogenic
      mutation. This molecular diagnosis allows us to provide genetic counseling to the
      family and eventually propose prenatal diagnosis to prevent recurrence of the
      disease in subsequent pregnancies. 

PMID- 25852445
TI  - Clinical and molecular heterogeneity in brazilian patients with sotos syndrome.
AB  - Sotos syndrome (SoS) is a multiple anomaly, congenital disorder characterized by
      overgrowth, macrocephaly, distinctive facial features and variable degree of
      intellectual disability. Haploinsufficiency of the NSD1 gene at 5q35.3, arising
      from 5q35 microdeletions, point mutations, and partial gene deletions, accounts
      for a majority of patients with SoS. Recently, mutations and possible
      pathogenetic rare CNVs, both affecting a few candidate genes for overgrowth, have
      been reported in patients with Sotos-like overgrowth features. To estimate the
      frequency of NSD1 defects in the Brazilian SoS population and possibly reveal
      other genes implicated in the etiopathogenesis of this syndrome, we collected a
      cohort of 21 Brazilian patients, who fulfilled the diagnostic criteria for SoS,
      and analyzed the NSD1 and PTEN genes by means of multiplex ligation-dependent
      probe amplification and mutational screening analyses. We identified a classical
      NSD1 microdeletion, a novel missense mutation (p.C1593W), and 2 previously
      reported truncating mutations: p.R1984X and p.V1760Gfs*2. In addition, we
      identified a novel de novo PTEN gene mutation (p.D312Rfs*2) in a patient with a
      less severe presentation of SoS phenotype, which did not include pre- and
      postnatal overgrowth. For the first time, our study implies PTEN in the
      pathogenesis of SoS and further emphasizes the existence of ethno-geographical
      differences in NSD1 molecular alterations between patients with SoS from
      Europe/North America (70-93%) and those from South America (10-19%). 

PMID- 25852448
TI  - A Glutamine Repeat Variant of the RUNX2 Gene Causes Cleidocranial Dysplasia.
AB  - Cleidocranial dysplasia (CCD), an autosomal dominant skeletal dysplasia
      characterized by hypoplastic clavicles and delayed closure of the cranial
      sutures, is caused by mutations of the runt-related transcription factor 2
      (RUNX2) gene. The RUNX2 gene consists of a glutamine and alanine repeat domain
      (Q/A domain, 23Q/17A), a DNA-binding Runt domain and a proline/serine/threonine
      rich domain. We report on a familial case of CCD with a novel mutation within the
      Q/A domain of the RUNX2 gene, which is an insertion in exon 1 (p.Q71_E72insQQQQ)
      representing the Q-repeat variant (27Q/17A). Functional analysis of the 27Q
      variant revealed abolished transactivation capacity of the mutated RUNX2 protein.
      This is the first case report that demonstrated a glutamine repeat variant of the
      RUNX2 gene causes CCD. 

PMID- 25852449
TI  - Structural brain abnormalities in postural tachycardia syndrome: A VBM-DARTEL
      study.
AB  - Postural tachycardia syndrome (PoTS), a form of dysautonomia, is characterized by
      orthostatic intolerance, and is frequently accompanied by a range of symptoms
      including palpitations, lightheadedness, clouding of thought, blurred vision,
      fatigue, anxiety, and depression. Although the estimated prevalence of PoTS is
      approximately 5-10 times as common as the better-known condition orthostatic
      hypotension, the neural substrates of the syndrome are poorly characterized. In
      the present study, we used magnetic resonance imaging (MRI) with voxel-based
      morphometry (VBM) applying the diffeomorphic anatomical registration through
      exponentiated lie algebra (DARTEL) procedure to examine variation in regional
      brain structure associated with PoTS. We recruited 11 patients with established
      PoTS and 23 age-matched normal controls. Group comparison of gray matter volume
      revealed diminished gray matter volume within the left anterior insula, right
      middle frontal gyrus and right cingulate gyrus in the PoTS group. We also
      observed lower white matter volume beneath the precentral gyrus and paracentral
      lobule, right pre- and post-central gyrus, paracentral lobule and superior
      frontal gyrus in PoTS patients. Subsequent ROI analyses revealed significant
      negative correlations between left insula volume and trait anxiety and depression
      scores. Together, these findings of structural differences, particularly within
      insular and cingulate components of the salience network, suggest a link between
      dysregulated physiological reactions arising from compromised central autonomic
      control (and interoceptive representation) and increased vulnerability to
      psychiatric symptoms in PoTS patients. 

PMID- 25852450
TI  - Amyloid-beta oligomers unveil a novel primate model of sporadic Alzheimer's
      disease.

PMID- 25852452
TI  - Cognitive mechanisms underlying instructed choice exploration of small city maps.
AB  - We investigated the cognitive mechanisms underlying the exploration and decision
      making in realistic and novel environments. Twelve human subjects were shown
      small circular U.S. city maps with two locations highlighted on the
      circumference, as possible choices for a post office ("targets"). At the
      beginning of a trial, subjects fixated a spot at the center of the map and
      ultimately chose one of the two locations. A space syntax analysis of the map
      paths (from the center to each target) revealed that the chosen location was
      associated with the less convoluted path, as if subjects navigated mentally the
      paths in an "ant's way," i.e., by staying within street boundaries, and
      ultimately choosing the target that could be reached from the center in the
      shortest way, and the fewest turns and intersections. The subjects' strategy for
      map exploration and decision making was investigated by monitoring eye position
      during the task. This revealed a restricted exploration of the map delimited by
      the location of the two alternative options and the center of the map.
      Specifically, subjects explored the areas around the two target options by
      repeatedly looking at them before deciding which one to choose, presumably
      implementing an evaluation and decision-making process. The ultimate selection of
      a specific target was significantly associated with the time spent exploring the
      area around that target. Finally, an analysis of the sequence of eye fixations
      revealed that subjects tended to look systematically toward the target ultimately
      chosen even from the beginning of the trial. This finding indicates an early
      cognitive selection bias for the ensuing decision process. 

PMID- 25852451
TI  - The ecology of human fear: survival optimization and the nervous system.
AB  - We propose a Survival Optimization System (SOS) to account for the strategies
      that humans and other animals use to defend against recurring and novel threats.
      The SOS attempts to merge ecological models that define a repertoire of
      contextually relevant threat induced survival behaviors with contemporary
      approaches to human affective science. We first propose that the goal of the
      nervous system is to reduce surprise and optimize actions by (i) predicting the
      sensory landscape by simulating possible encounters with threat and selecting the
      appropriate pre-encounter action and (ii) prevention strategies in which the
      organism manufactures safe environments. When a potential threat is encountered
      the (iii) threat orienting system is engaged to determine whether the organism
      ignores the stimulus or switches into a process of (iv) threat assessment, where
      the organism monitors the stimulus, weighs the threat value, predicts the actions
      of the threat, searches for safety, and guides behavioral actions crucial to
      directed escape. When under imminent attack, (v) defensive systems evoke fast
      reflexive indirect escape behaviors (i.e., fight or flight). This cascade of
      responses to threat of increasing magnitude are underwritten by an interconnected
      neural architecture that extends from cortical and hippocampal circuits, to
      attention, action and threat systems including the amygdala, striatum, and hard
      wired defensive systems in the midbrain. The SOS also includes a modulatory
      feature consisting of cognitive appraisal systems that flexibly guide perception,
      risk and action. Moreover, personal and vicarious threat encounters fine-tune
      avoidance behaviors via model-based learning, with higher organisms bridging data
      to reduce face-to-face encounters with predators. Our model attempts to unify the
      divergent field of human affective science, proposing a highly integrated nervous
      system that has evolved to increase the organism's chances of survival. 

PMID- 25852453
TI  - Estradiol-sensitive projection neurons in the female rat preoptic area.
AB  - Electrical stimulation of the preoptic area (POA) interrupts the lordosis reflex,
      a combined contraction of back muscles, in response to male mounts and the major
      receptive component of sexual behavior in female rat in estrus, without
      interfering with the proceptive component of this behavior or solicitation. Axon
      sparing POA lesions with an excitotoxin, on the other hand, enhance lordosis and
      diminish proceptivity. The POA effect on the reflex is mediated by its estrogen
      sensitive projection to the ventral tegmental area (VTA) as shown by the
      behavioral effect of VTA stimulation as well as by the demonstration of an
      increased threshold for antidromic activation of POA neurons from the VTA in
      ovariectomized females treated with estradiol benzoate (EB). EB administration
      increases the antidromic activation threshold in ovariectomized females and
      neonatally castrated males, but not in neonatally androgenized females; the EB
      effect is limited to those that show lordosis in the presence of EB. EB causes
      behavioral disinhibition of lordosis through an inhibition of POA neurons with
      axons to the VTA, which eventually innervate medullospinal neurons innervating
      spinal motoneurons of the back muscle. The EB-induced change in the threshold or
      the axonal excitability may be a result of EB-dependent induction of BK channels.
      Recordings from freely moving female rats engaging in sexual interactions
      revealed separate subpopulations of POA neurons for the receptive and proceptive
      behaviors. Those POA neurons engaging in the control of proceptivity are EB
      sensitive and project to the midbrain locomotor region (MLR). EB thus enhances
      lordosis by reducing excitatory neural impulses from the POA to the VTA. An
      augmentation of the POA effect to the MLR may culminate in an increased
      locomotion that embodies behavioral estrus in the female rat. 

PMID- 25852454
TI  - Spinal primitives and intra-spinal micro-stimulation (ISMS) based prostheses: a
      neurobiological perspective on the "known unknowns" in ISMS and future prospects.
AB  - The current literature on Intra-Spinal Micro-Stimulation (ISMS) for motor
      prostheses is reviewed in light of neurobiological data on spinal organization,
      and a neurobiological perspective on output motor modularity, ISMS maps,
      stimulation combination effects, and stability. By comparing published data in
      these areas, the review identifies several gaps in current knowledge that are
      crucial to the development of effective intraspinal neuroprostheses. Gaps can be
      categorized into a lack of systematic and reproducible details of: (a) Topography
      and threshold for ISMS across the segmental motor system, the topography of
      autonomic recruitment by ISMS, and the coupling relations between these two types
      of outputs in practice. (b) Compositional rules for ISMS motor responses tested
      across the full range of the target spinal topographies. (c) Rules for ISMS
      effects' dependence on spinal cord state and neural dynamics during naturally
      elicited or ISMS triggered behaviors. (d) Plasticity of the compositional rules
      for ISMS motor responses, and understanding plasticity of ISMS topography in
      different spinal cord lesion states, disease states, and following
      rehabilitation. All these knowledge gaps to a greater or lesser extent require
      novel electrode technology in order to allow high density chronic recording and
      stimulation. The current lack of this technology may explain why these prominent
      gaps in the ISMS literature currently exist. It is also argued that given the
      "known unknowns" in the current ISMS literature, it may be prudent to adopt and
      develop control schemes that can manage the current results with simple
      superposition and winner-take-all interactions, but can also incorporate the
      possible plastic and stochastic dynamic interactions that may emerge in fuller
      analyses over longer terms, and which have already been noted in some simpler
      model systems. 

PMID- 25852455
TI  - Effect of social odor context on the emission of isolation-induced ultrasonic
      vocalizations in the BTBR T+tf/J mouse model for autism.
AB  - An important diagnostic criterion for social communication deficits in autism
      spectrum disorders (ASD) are difficulties in adjusting behavior to suit different
      social contexts. While the BTBR T+tf/J (BTBR) inbred strain of mice is one of the
      most commonly used mouse models for ASD, little is known about whether BTBR mice
      display deficits in detecting changes in social context and their ability to
      adjust to them. Here, it was tested therefore whether the emission of isolation
      induced ultrasonic vocalizations (USV) in BTBR mouse pups is affected by the
      social odor context, in comparison to the standard control strain with high
      sociability, C57BL/6J (B6). It is known that the presence of odors from mothers
      and littermates leads to a calming of the isolated mouse pup, and hence to a
      reduction in isolation-induced USV emission. In accordance with their behavioral
      phenotypes with relevance to all diagnostic core symptoms of ASD, it was
      predicted that BTBR mouse pups would not display a calming response when tested
      under soiled bedding conditions with home cage bedding material containing
      maternal odors, and that similar isolation-induced USV emission rates would be
      seen in BTBR mice tested under clean and soiled bedding conditions. Unexpectedly,
      however, the present findings show that BTBR mouse pups display such a calming
      response and emit fewer isolation-induced USV when tested under soiled as
      compared to clean bedding conditions, similar to B6 mouse pups. Yet, in contrast
      to B6 mouse pups, which emitted isolation-induced USV with shorter call durations
      and lower levels of frequency modulation under soiled bedding conditions, social
      odor context had no effect on acoustic call features in BTBR mouse pups. This
      indicates that the BTBR mouse model for ASD does not display deficits in
      detecting changes in social context, but has a limited ability and/or reduced
      motivation to adjust to them. 

PMID- 25852456
TI  - Outer brain barriers in rat and human development.
AB  - Complex barriers at the brain's surface, particularly in development, are poorly
      defined. In the adult, arachnoid blood-cerebrospinal fluid (CSF) barrier
      separates the fenestrated dural vessels from the CSF by means of a cell layer
      joined by tight junctions. Outer CSF-brain barrier provides diffusion restriction
      between brain and subarachnoid CSF through an initial radial glial end feet layer
      covered with a pial surface layer. To further characterize these interfaces we
      examined embryonic rat brains from E10 to P0 and forebrains from human embryos
      and fetuses (6-21st weeks post-conception) and adults using immunohistochemistry
      and confocal microscopy. Antibodies against claudin-11, BLBP, collagen 1, SSEA-4,
      MAP2, YKL-40, and its receptor IL-13Ralpha2 and EAAT1 were used to describe
      morphological characteristics and functional aspects of the outer brain barriers.
      Claudin-11 was a reliable marker of the arachnoid blood-CSF barrier. Collagen 1
      delineated the subarachnoid space and stained pial surface layer. BLBP defined
      radial glial end feet layer and SSEA-4 and YKL-40 were present in both
      leptomeningeal cells and end feet layer, which transformed into glial limitans.
      IL-13Ralpha2 and EAAT1 were present in the end feet layer illustrating
      transporter/receptor presence in the outer CSF-brain barrier. MAP2 immunostaining
      in adult brain outlined the lower border of glia limitans; remnants of end feet
      were YKL-40 positive in some areas. We propose that outer brain barriers are
      composed of at least 3 interfaces: blood-CSF barrier across arachnoid barrier
      cell layer, blood-CSF barrier across pial microvessels, and outer CSF-brain
      barrier comprising glial end feet layer/pial surface layer. 

PMID- 25852457
TI  - Functional significance of the electrocorticographic auditory responses in the
      premotor cortex.
AB  - Other than well-known motor activities in the precentral gyrus, functional
      magnetic resonance imaging (fMRI) studies have found that the ventral part of the
      precentral gyrus is activated in response to linguistic auditory stimuli. It has
      been proposed that the premotor cortex in the precentral gyrus is responsible for
      the comprehension of speech, but the precise function of this area is still
      debated because patients with frontal lesions that include the precentral gyrus
      do not exhibit disturbances in speech comprehension. We report on a patient who
      underwent resection of the tumor in the precentral gyrus with
      electrocorticographic recordings while she performed the verb generation task
      during awake brain craniotomy. Consistent with previous fMRI studies, high-gamma
      band auditory activity was observed in the precentral gyrus. Due to the location
      of the tumor, the patient underwent resection of the auditory responsive
      precentral area which resulted in the post-operative expression of a
      characteristic articulatory disturbance known as apraxia of speech (AOS). The
      language function of the patient was otherwise preserved and she exhibited intact
      comprehension of both spoken and written language. The present findings
      demonstrated that a lesion restricted to the ventral precentral gyrus is
      sufficient for the expression of AOS and suggest that the auditory-responsive
      area plays an important role in the execution of fluent speech rather than the
      comprehension of speech. These findings also confirm that the function of the
      premotor area is predominantly motor in nature and its sensory responses is more
      consistent with the "sensory theory of speech production," in which it was
      proposed that sensory representations are used to guide motor-articulatory
      processes. 

PMID- 25852458
TI  - Effects of diethylstilbestrol exposure during gestation on both maternal and
      offspring behavior.
AB  - Endocrine disruption during gestation impairs the physical and behavioral
      development of offspring. However, it is unclear whether endocrine disruption
      also impairs maternal behavior and in turn further contributes to the
      developmental and behavioral dysfunction of offspring. We orally administered the
      synthetic non-steroidal estrogen diethylstilbestrol (DES) to pregnant female
      C57BL/6J mice from gestation day 11-17 and then investigated the maternal
      behavior of mothers. In addition, we examined the direct effects of in utero DES
      exposure and the indirect effects of aberrant maternal behavior on offspring
      using the cross-fostering method. In mothers, endocrine disruption during
      gestation decreased maternal behavior. In addition, endocrine disruption of
      foster mother influenced anxiety-related behavior and passive avoidance learning
      of pups regardless of their exposure in utero. The influence of DES exposure in
      utero, irrespective of exposure to the foster mother, was also shown in female
      offspring. These results demonstrate the risks of endocrine disruptors on both
      mother as well as offspring and suggest that developmental deficits may stem from
      both in utero toxicity and aberrant maternal care. 

PMID- 25852459
TI  - Local modulation of steroid action: rapid control of enzymatic activity.
AB  - Estrogens can induce rapid, short-lived physiological and behavioral responses,
      in addition to their slow, but long-term, effects at the transcriptional level.
      To be functionally relevant, these effects should be associated with rapid
      modulations of estrogens concentrations. 17beta-estradiol is synthesized by the
      enzyme aromatase, using testosterone as a substrate, but can also be degraded
      into catechol-estrogens via hydroxylation by the same enzyme, leading to an
      increase or decrease in estrogens concentration, respectively. The first evidence
      that aromatase activity (AA) can be rapidly modulated came from experiments
      performed in Japanese quail hypothalamus homogenates. This rapid modulation is
      triggered by calcium-dependent phosphorylations and was confirmed in other
      tissues and species. The mechanisms controlling the phosphorylation status, the
      targeted amino acid residues and the reversibility seem to vary depending of the
      tissues and is discussed in this review. We currently do not know whether the
      phosphorylation of the same amino acid affects both aromatase and/or hydroxylase
      activities or whether these residues are different. These processes provide a new
      general mechanism by which local estrogen concentration can be rapidly altered in
      the brain and other tissues. 

PMID- 25852460
TI  - The role of metabotropic glutamate receptor 5 in the pathogenesis of mood
      disorders and addiction: combining preclinical evidence with human Positron
      Emission Tomography (PET) studies.
AB  - In the present review, we deliver an overview of the involvement of metabotropic
      glutamate receptor 5 (mGluR5) activity and density in pathological anxiety, mood
      disorders and addiction. Specifically, we will describe mGluR5 studies in humans
      that employed Positron Emission Tomography (PET) and combined the findings with
      preclinical animal research. This combined view of different methodological
      approaches-from basic neurobiological approaches to human studies-might give a
      more comprehensive and clinically relevant view of mGluR5 function in mental
      health than the view on preclinical data alone. We will also review the current
      research data on mGluR5 along the Research Domain Criteria (RDoC). Firstly, we
      found evidence of abnormal glutamate activity related to the positive and
      negative valence systems, which would suggest that antagonistic mGluR5
      intervention has prominent anti-addictive, anti-depressive and anxiolytic
      effects. Secondly, there is evidence that mGluR5 plays an important role in
      systems for social functioning and the response to social stress. Finally,
      mGluR5's important role in sleep homeostasis suggests that this glutamate
      receptor may play an important role in RDoC's arousal and modulatory systems
      domain. Glutamate was previously mostly investigated in non-human studies,
      however initial human clinical PET research now also supports the hypothesis
      that, by mediating brain excitability, neuroplasticity and social cognition,
      abnormal metabotropic glutamate activity might predispose individuals to a broad
      range of psychiatric problems. 

PMID- 25852461
TI  - Spatiotemporal analyses of neural lineages after embryonic and postnatal
      progenitor targeting combining different reporters.
AB  - Genetic lineage tracing with electroporation is one of the most powerful
      techniques to target neural progenitor cells and their progeny. However, the
      spatiotemporal relationship between neural progenitors and their final phenotype
      remain poorly understood. One critical factor to analyze the cell fate of progeny
      is reporter integration into the genome of transfected cells. To address this
      issue, we performed postnatal and in utero co-electroporations of different
      fluorescent reporters to label, in both cerebral cortex and olfactory bulb, the
      progeny of subventricular zone neural progenitors. By comparing fluorescent
      reporter expression in the adult cell progeny, we show a differential expression
      pattern within the same cell lineage, depending on electroporation stage and cell
      identity. Further, while neuronal lineages arise from many progenitors in
      proliferative zones after few divisions, glial lineages come from fewer
      progenitors that accomplish many cell divisions. Together, these data provide a
      useful guide to select a strategy to track the cell fate of a specific cell
      population and to address whether a different proliferative origin might be
      correlated with functional heterogeneity. 

PMID- 25852462
TI  - Collaborative mining of public data resources in neuroinformatics.

PMID- 25852465
TI  - Corrigendum: Hypothalamic miRNAs: emerging roles in energy balance control.
AB  - [This corrects the article on p. 41 in vol. 9, PMID: 25729348.]. 

PMID- 25852464
TI  - Neurotoxic effects of AZT on developing and adult neurogenesis.
AB  - Azidothymidine (AZT) is a synthetic, chain-terminating nucleoside analog used to
      treat HIV-1 infection. While AZT is not actively transported across the blood
      brain barrier, it does accumulate at high levels in cerebrospinal fluid, and
      subsequently diffuses into the overlying parenchyma. Due to the close anatomical
      proximity of the neurogenic niches to the ventricular system, we hypothesize that
      diffusion from CSF exposes neural stem/progenitor cells and their progeny to
      biologically relevant levels of AZT sufficient to perturb normal cell functions.
      We employed in vitro and in vivo models of mouse neurogenesis in order to assess
      the effects of AZT on developing and adult neurogenesis. Using in vitro assays we
      show that AZT reduces the population expansion potential of neural
      stem/progenitor cells by inducing senescence. Additionally, in a model of in
      vitro neurogenesis AZT severely attenuates neuroblast production. These effects
      are mirrored in vivo by clinically-relevant animal models. We show that in utero
      AZT exposure perturbs both population expansion and neurogenesis among neural
      stem/progenitor cells. Additionally, a short-term AZT regimen in adult mice
      suppresses subependymal zone neurogenesis. These data reveal novel negative
      effects of AZT on neural stem cell biology. Given that the sequelae of HIV
      infection often include neurologic deficits-subsumed under AIDS Dementia Complex
      (Brew, 1999)-it is important to determine to what extent AZT negatively affects
      neurological function in ways that contribute to, or exacerbate, ADC in order to
      avoid attributing iatrogenic drug effects to the underlying disease process, and
      thereby skewing the risk/benefit analysis of AZT therapy. 

PMID- 25852463
TI  - GLP-1 based therapeutics: simultaneously combating T2DM and obesity.
AB  - Glucagon-like peptide-1 (GLP-1) enhances meal-related insulin secretion, which
      lowers blood glucose excursions. In addition to its incretin action, GLP-1 acts
      on the GLP-1 receptor (GLP-1R) in the brain to suppress feeding. These combined
      actions of GLP-1R signaling cause improvements in glycemic control as well as
      weight loss in type II diabetes (T2DM) patients treated with GLP-1R agonists.
      This is a superior advantage of GLP-1R pharmaceuticals as many other drugs used
      to treat T2DM are weight neutral or actual cause weight gain. This review
      summarizes GLP-1R action on energy and glucose metabolism, the effectiveness of
      current GLP-1R agonists on weight loss in T2DM patients, as well as GLP-1R
      combination therapies. 

PMID- 25852466
TI  - Proteoglycans and neuronal migration in the cerebral cortex during development
      and disease.
AB  - Chondroitin sulfate proteoglycans and heparan sulfate proteoglycans are major
      constituents of the extracellular matrix and the cell surface in the brain.
      Proteoglycans bind with many proteins including growth factors, chemokines, axon
      guidance molecules, and cell adhesion molecules through both the
      glycosaminoglycan and the core protein portions. The functions of proteoglycans
      are flexibly regulated due to the structural variability of glycosaminoglycans,
      which are generated by multiple glycosaminoglycan synthesis and modifying
      enzymes. Neuronal cell surface proteoglycans such as PTPzeta, neuroglycan C and
      syndecan-3 function as direct receptors for heparin-binding growth factors that
      induce neuronal migration. The lectican family, secreted chondroitin sulfate
      proteoglycans, forms large aggregates with hyaluronic acid and tenascins, in
      which many signaling molecules and enzymes including matrix proteases are
      preserved. In the developing cerebrum, secreted chondroitin sulfate proteoglycans
      such as neurocan, versican and phosphacan are richly expressed in the areas that
      are strategically important for neuronal migration such as the striatum, marginal
      zone, subplate and subventricular zone in the neocortex. These proteoglycans may
      anchor various attractive and/or repulsive cues, regulating the migration routes
      of inhibitory neurons. Recent studies demonstrated that the genes encoding
      proteoglycan core proteins and glycosaminoglycan synthesis and modifying enzymes
      are associated with various psychiatric and intellectual disorders, which may be
      related to the defects of neuronal migration. 

PMID- 25852468
TI  - Non-additive modulation of synaptic transmission by serotonin, adenosine, and
      cholinergic modulators in the sensory thalamus.
AB  - The thalamus relays sensory information to the cortex. Oscillatory activities of
      the thalamocortical network are modulated by monoamines, acetylcholine, and
      adenosine, and could be the key features characteristic of different vigilance
      states. Although the thalamus is almost always subject to the actions of more
      than just one neuromodulators, reports on the modulatory effect of coexisting
      neuromodulators on thalamic synaptic transmission are unexpectedly scarce. We
      found that, if present alone, monoamine or adenosine decreases retinothalamic
      synaptic strength and short-term depression, whereas cholinergic modulators
      generally enhance postsynaptic response to presynaptic activity. However,
      coexistence of different modulators tends to produce non-additive effect, not
      predictable based on the action of individual modulators. Acetylcholine, acting
      via nicotinic receptors, can interact with either serotonin or adenosine to
      abolish most short-term synaptic depression. Moreover, the coexistence of
      adenosine and monoamine, with or without acetylcholine, results in robustly
      decreased synaptic strength and transforms short-term synaptic depression to
      facilitation. These findings are consistent with a view that acetylcholine is
      essential for an "enriched" sensory flow through the thalamus, and the flow is
      trimmed down by concomitant monoamine or adenosine (presumably for the
      wakefulness and rapid-eye movement, or REM, sleep states, respectively). In
      contrast, concomitant adenosine and monoamine would lead to a markedly "deprived"
      (and high-pass filtered) sensory flow, and thus the dramatic decrease of
      monoamine may constitute the basic demarcation between non-REM and REM sleep. The
      collective actions of different neuromodulators on thalamic synaptic transmission
      thus could be indispensable for the understanding of network responsiveness in
      different vigilance states. 

PMID- 25852469
TI  - Polarity transitions during neurogenesis and germinal zone exit in the developing
      central nervous system.
AB  - During neural development, billions of neurons differentiate, polarize, migrate
      and form synapses in a precisely choreographed sequence. These precise
      developmental events are accompanied by discreet transitions in cellular
      polarity. While radial glial neural stem cells are highly polarized, transiently
      amplifying neural progenitors are less polarized after delaminating from their
      parental stem cell. Moreover, preceding their radial migration to a final laminar
      position neural progenitors re-adopt a polarized morphology before they embarking
      on their journey along a glial guide to the destination where they will fully
      mature. In this review, we will compare and contrast the key polarity transitions
      of cells derived from a neuroepithelium to the well-characterized polarity
      transitions that occur in true epithelia. We will highlight recent advances in
      the field that shows that neuronal progenitor delamination from germinal zone
      (GZ) niche shares similarities to an epithelial-mesenchymal transition. Moreover,
      studies in the cerebellum suggest the acquisition of radial migration and
      polarity in transiently amplifying neural progenitors share similarities to
      mesenchymal-epithelial transitions. Where applicable, we will compare and
      contrast the precise molecular mechanisms used by epithelial cells and neuronal
      progenitors to control plasticity in cell polarity during their distinct
      developmental programs. 

PMID- 25852470
TI  - Contribution of sublinear and supralinear dendritic integration to neuronal
      computations.
AB  - Nonlinear dendritic integration is thought to increase the computational ability
      of neurons. Most studies focus on how supralinear summation of excitatory
      synaptic responses arising from clustered inputs within single dendrites result
      in the enhancement of neuronal firing, enabling simple computations such as
      feature detection. Recent reports have shown that sublinear summation is also a
      prominent dendritic operation, extending the range of subthreshold input-output
      (sI/O) transformations conferred by dendrites. Like supralinear operations,
      sublinear dendritic operations also increase the repertoire of neuronal
      computations, but feature extraction requires different synaptic connectivity
      strategies for each of these operations. In this article we will review the
      experimental and theoretical findings describing the biophysical determinants of
      the three primary classes of dendritic operations: linear, sublinear, and
      supralinear. We then review a Boolean algebra-based analysis of simplified neuron
      models, which provides insight into how dendritic operations influence neuronal
      computations. We highlight how neuronal computations are critically dependent on
      the interplay of dendritic properties (morphology and voltage-gated channel
      expression), spiking threshold and distribution of synaptic inputs carrying
      particular sensory features. Finally, we describe how global (scattered) and
      local (clustered) integration strategies permit the implementation of similar
      classes of computations, one example being the object feature binding problem. 

PMID- 25852467
TI  - A network of RNA and protein interactions in Fronto Temporal Dementia.
AB  - Frontotemporal dementia (FTD) is a neurodegenerative disorder characterized by
      degeneration of the fronto temporal lobes and abnormal protein inclusions. It
      exhibits a broad clinicopathological spectrum and has been linked to mutations in
      seven different genes. We will provide a picture, which connects the products of
      these genes, albeit diverse in nature and function, in a network. Despite the
      paucity of information available for some of these genes, we believe that RNA
      processing and post-transcriptional regulation of gene expression might
      constitute a common theme in the network. Recent studies have unraveled the role
      of mutations affecting the functions of RNA binding proteins and regulation of
      microRNAs. This review will combine all the recent findings on genes involved in
      the pathogenesis of FTD, highlighting the importance of a common network of
      interactions in order to study and decipher the heterogeneous clinical
      manifestations associated with FTD. This approach could be helpful for the
      research of potential therapeutic strategies. 

PMID- 25852471
TI  - The neural stem cell fate determinant TRIM32 regulates complex behavioral traits.
AB  - In mammals, new neurons are generated throughout the entire lifespan in two
      restricted areas of the brain, the dentate gyrus (DG) of the hippocampus and the
      subventricular zone (SVZ)-olfactory bulb (OB) system. In both regions newborn
      neurons display unique properties that clearly distinguish them from mature
      neurons. Enhanced excitability and increased synaptic plasticity enables them to
      add specific properties to information processing by modulating the existing
      local circuitry of already established mature neurons. Hippocampal neurogenesis
      has been suggested to play a role in spatial-navigation learning, spatial memory,
      and spatial pattern separation. Cumulative evidences implicate that adult-born OB
      neurons contribute to learning processes and odor memory. We recently
      demonstrated that the cell fate determinant TRIM32 is upregulated in
      differentiating neuroblasts of the SVZ-OB system in the adult mouse brain. The
      absence of TRIM32 leads to increased progenitor cell proliferation and less cell
      death. Both effects accumulate in an overproduction of adult-generated OB
      neurons. Here, we present novel data from behavioral studies showing that such an
      enhancement of OB neurogenesis not necessarily leads to increased olfactory
      performance but in contrast even results in impaired olfactory capabilities. In
      addition, we show at the cellular level that TRIM32 protein levels increase
      during differentiation of neural stem cells (NSCs). At the molecular level,
      several metabolic intermediates that are connected to glycolysis, glycine, or
      cysteine metabolism are deregulated in TRIM32 knockout mice brain tissue. These
      metabolomics pathways are directly or indirectly linked to anxiety or depression
      like behavior. In summary, our study provides comprehensive data on how the
      impairment of neurogenesis caused by the loss of the cell fate determinant TRIM32
      causes a decrease of olfactory performance as well as a deregulation of
      metabolomic pathways that are linked to mood disorders. 

PMID- 25852472
TI  - Astrocyte heterogeneity in the brain: from development to disease.
AB  - In the last decades, astrocytes have risen from passive supporters of neuronal
      activity to central players in brain function and cognition. Likewise, the
      heterogeneity of astrocytes starts to become recognized in contrast to the
      homogeneous population previously predicted. In this review, we focused on
      astrocyte heterogeneity in terms of their morphological, protein expression and
      functional aspects, and debate in a historical perspective the diversity
      encountered in glial progenitors and how they may reflect mature astrocyte
      heterogeneity. We discussed data that show that different progenitors may have
      unsuspected roles in developmental processes. We have approached the functions of
      astrocyte subpopulations on the onset of psychiatric and neurological diseases. 

PMID- 25852473
TI  - Alteration of synaptic connectivity of oligodendrocyte precursor cells following
      demyelination.
AB  - Oligodendrocyte precursor cells (OPCs) are a major source of remyelinating
      oligodendrocytes in demyelinating diseases such as Multiple Sclerosis (MS). While
      OPCs are innervated by unmyelinated axons in the normal brain, the fate of such
      synaptic contacts after demyelination is still unclear. By combining
      electrophysiology and immunostainings in different transgenic mice expressing
      fluorescent reporters, we studied the synaptic innervation of OPCs in the model
      of lysolecithin (LPC)-induced demyelination of corpus callosum. Synaptic
      innervation of reactivated OPCs in the lesion was revealed by the presence of
      AMPA receptor-mediated synaptic currents, VGluT1+ axon-OPC contacts in 3D
      confocal reconstructions and synaptic junctions observed by electron microscopy.
      Moreover, 3D confocal reconstructions of VGluT1 and NG2 immunolabeling showed the
      existence of glutamatergic axon-OPC contacts in post-mortem MS lesions.
      Interestingly, patch-clamp recordings in LPC-induced lesions demonstrated a
      drastic decrease in spontaneous synaptic activity of OPCs early after
      demyelination that was not caused by an impaired conduction of compound action
      potentials. A reduction in synaptic connectivity was confirmed by the lack of
      VGluT1+ axon-OPC contacts in virtually all rapidly proliferating OPCs stained
      with EdU (50-ethynyl-20-deoxyuridine). At the end of the massive proliferation
      phase in lesions, the proportion of innervated OPCs rapidly recovers, although
      the frequency of spontaneous synaptic currents did not reach control levels. In
      conclusion, our results demonstrate that newly-generated OPCs do not receive
      synaptic inputs during their active proliferation after demyelination, but gain
      synapses during the remyelination process. Hence, glutamatergic synaptic inputs
      may contribute to inhibit OPC proliferation and might have a physiopathological
      relevance in demyelinating disorders. 

PMID- 25852474
TI  - PPARbeta/delta and PPARgamma maintain undifferentiated phenotypes of mouse adult
      neural precursor cells from the subventricular zone.
AB  - The subventricular zone (SVZ) is one of the main niches of neural stem cells in
      the adult mammalian brain. Stem and precursor cells in this region are the source
      for neurogenesis and oligodendrogesis, mainly in the olfactory bulb and corpus
      callosum, respectively. The identification of the molecular components regulating
      the decision of these cells to differentiate or maintain an undifferentiated
      state is important in order to understand the modulation of neurogenic processes
      in physiological and pathological conditions. PPARs are a group of transcription
      factors, activated by lipid ligands, with important functions in cellular
      differentiation and proliferation in several tissues. In this work, we
      demonstrate that mouse adult neural precursor cells (NPCs), in situ and in vitro,
      express PPARbeta/delta and PPARgamma. Pharmacological activation of both PPARs
      isoforms induces proliferation and maintenance of the undifferentiated phenotype.
      Congruently, inhibition of PPARbeta/delta and PPARgamma results in a decrease of
      proliferation and loss of the undifferentiated phenotype. Interestingly,
      PPARgamma regulates the level of EGFR in adult NPCs, concurrent with it is
      function described in embryonic NPCs. Furthermore, we describe for the first time
      that PPARbeta/delta regulates SOX2 level in adult NPCs, probably through a direct
      transcriptional regulation, as we identified two putative PPAR response elements
      in the promoter region of Sox2. EGFR and SOX2 are key players in neural
      stem/precursor cells self-renewal. Finally, rosiglitazone, a PPARgamma ligand,
      increases PPARbeta/delta level, suggesting a possible cooperation between these
      two PPARs in the control of cell fate behavior. Our work contributes to the
      understanding of the molecular mechanisms associated to neural cell fate decision
      and places PPARbeta/delta and PPARgamma as interesting new targets of modulation
      of mammalian brain homeostasis. 

PMID- 25852475
TI  - Identification and characterization of mouse otic sensory lineage genes.
AB  - Vertebrate embryogenesis gives rise to all cell types of an organism through the
      development of many unique lineages derived from the three primordial germ
      layers. The otic sensory lineage arises from the otic vesicle, a structure formed
      through invagination of placodal non-neural ectoderm. This developmental lineage
      possesses unique differentiation potential, giving rise to otic sensory cell
      populations including hair cells, supporting cells, and ganglion neurons of the
      auditory and vestibular organs. Here we present a systematic approach to identify
      transcriptional features that distinguish the otic sensory lineage (from early
      otic progenitors to otic sensory populations) from other major lineages of
      vertebrate development. We used a microarray approach to analyze otic sensory
      lineage populations including microdissected otic vesicles (embryonic day 10.5)
      as well as isolated neonatal cochlear hair cells and supporting cells at
      postnatal day 3. Non-otic tissue samples including periotic tissues and whole
      embryos with otic regions removed were used as reference populations to evaluate
      otic specificity. Otic populations shared transcriptome-wide correlations in
      expression profiles that distinguish members of this lineage from non-otic
      populations. We further analyzed the microarray data using comparative and
      dimension reduction methods to identify individual genes that are specifically
      expressed in the otic sensory lineage. This analysis identified and ranked top
      otic sensory lineage-specific transcripts including Fbxo2, Col9a2, and Oc90, and
      additional novel otic lineage markers. To validate these results we performed
      expression analysis on select genes using immunohistochemistry and in situ
      hybridization. Fbxo2 showed the most striking pattern of specificity to the otic
      sensory lineage, including robust expression in the early otic vesicle and
      sustained expression in prosensory progenitors and auditory and vestibular hair
      cells and supporting cells. 

PMID- 25852476
TI  - PKCepsilon and allopregnanolone: functional cross-talk at the GABAA receptor
      level.
AB  - Changes in GABAergic inhibition occur during physiological processes, during
      response to drugs and in various pathologies. These changes can be achieved
      through direct allosteric modifications at the gamma-amino butyric acid (GABA)
      type A (GABAA) receptor protein level, or by altering the synthesis, trafficking
      and stability of the receptor. Neurosteroids (NSs) and protein kinase C (PKC) are
      potent modulators of GABAA receptors and their effects are presumably
      intermingled, even though evidence for this hypothesis is only partially
      explored. However, several PKC isoforms are able to phosphorylate the GABAA
      receptor, producing different functional effects. We focused on the epsilon
      isoform, that has been correlated to the sensitivity of the GABAA receptor to
      allosteric modulators and whose expression may be regulated in peripheral sensory
      neurons by NSs. The cross-talk between PKC-epsilon and NSs, leading to changes in
      GABAA receptor functionality, is considered and discussed in this perspective. 

PMID- 25852477
TI  - Cellular targets for neuropeptide Y-mediated control of adult neurogenesis.
AB  - Neuropeptides are emerging as key regulators of stem cell niche activities in
      health and disease, both inside and outside the central nervous system (CNS).
      Among them, neuropeptide Y (NPY), one of the most abundant neuropeptides both in
      the nervous system and in non-neural districts, has become the focus of much
      attention for its involvement in a wide range of physiological and pathological
      conditions, including the modulation of different stem cell activities. In
      particular, a pro-neurogenic role of NPY has been evidenced in the neurogenic
      niche, where a direct effect on neural progenitors has been demonstrated, while
      different cellular types, including astrocytes, microglia and endothelial cells,
      also appear to be responsive to the peptide. The marked modulation of the NPY
      system during several pathological conditions that affect neurogenesis, including
      stress, seizures and neurodegeneration, further highlights the relevance of this
      peptide in the regulation of adult neurogenesis. In view of the considerable
      interest in understanding the mechanisms controlling neural cell fate, this
      review aims to summarize and discuss current data on NPY signaling in the
      different cellular components of the neurogenic niche in order to elucidate the
      complexity of the mechanisms underlying the modulatory properties of this
      peptide. 

PMID- 25852479
TI  - Differential temporal expression of S100beta in developing rat brain.
AB  - Radial glial cells (RGs) originally considered to provide scaffold to the
      radially migrating neurons constitute a heterogeneous population of the
      regionally variable precursor cells that generate both neurons as well as glia
      depending upon the location and the timing of development. Hence specific
      immunohistochemical markers are required to specify their spatiotemporal location
      and fate in the neurogenic and gliogenic zones. We hypothesize S100beta as a
      potential and unified marker for both primary and secondary progenitors. To
      achieve this, cryocut sections from rat brains of varied embryonic and postnatal
      ages were immunolabeled with a combination of antibodies, i.e., S100beta +
      Nestin, Nestin + GFAP and S100beta + GFAP. A large population of the primary and
      secondary progenitors, lining the VZ and SVZ, simultaneously co-expressed
      S100beta and nestin establishing their progenitor nature. A downregulation of
      both S100beta and nestin noticed by the end of the 1st postnatal week marks their
      differentiation towards neuronal or glial lineage. In view of the absence of co
      expression of GFAP (glial fibrillary acidic protein) either with S100beta or
      nestin, the suitability of accepting GFAP as an early marker of RG's was
      eliminated. Thus the dynamic expression of S100beta in both the neural stem cells
      (NSCs) and RGs during embryonic and early neonatal life is associated with its
      proliferative potential and migration of undifferentiated neuroblasts and
      astrocytes. Once they lose their potential for proliferation, the S100beta
      expression is repressed with its reemergence in mature astrocytes. This study
      provides the first clear evidence of S100beta expression throughout the period of
      neurogenesis and early gliogenesis, suggesting its suitability as a radial
      progenitor cell marker. 

PMID- 25852478
TI  - Cancer as a channelopathy: ion channels and pumps in tumor development and
      progression.
AB  - Increasing evidence suggests that ion channels and pumps not only regulate
      membrane potential, ion homeostasis, and electric signaling in excitable cells
      but also play important roles in cell proliferation, migration, apoptosis and
      differentiation. Consistent with a role in cell signaling, channel proteins and
      ion pumps can form macromolecular complexes with growth factors, and cell
      adhesion and other signaling molecules. And while cancer is still not being
      cataloged as a channelopathy, as the non-traditional roles of ion pumps and
      channels are being recognized, it is increasingly being suggested that ion
      channels and ion pumps contribute to cancer progression. Cancer cell migration
      requires the regulation of adhesion complexes between migrating cells and
      surrounding extracellular matrix (ECM) proteins. Cell movement along solid
      surfaces requires a sequence of cell protrusions and retractions that mainly
      depend on regulation of the actin cytoskeleton along with contribution of
      microtubules and molecular motor proteins such as mysoin. This process is
      triggered and modulated by a combination of environmental signals, which are
      sensed and integrated by membrane receptors, including integrins and cadherins.
      Membrane receptors transduce these signals into downstream signaling pathways,
      often involving the Rho GTPase protein family. These pathways regulate the
      cytoskeletal rearrangements necessary for proper timing of adhesion, contraction
      and detachment of cells in order to find their way through extracellular spaces.
      Migration and adhesion involve continuous modulation of cell motility, shape and
      volume, in which ion channels and pumps play major roles. Research on cancer
      cells suggests that certain ion channels may be involved in aberrant tumor growth
      and channel inhibitors often lead to growth arrest. This review will describe
      recent research into the role of ion pumps and ion channels in cell migration and
      adhesion, and how they may contribute to tumor development. 

PMID- 25852480
TI  - An epigenetic hypothesis for the genomic memory of pain.
AB  - Chronic pain is accompanied with long-term sensory, affective and cognitive
      disturbances. What are the mechanisms that mediate the long-term consequences of
      painful experiences and embed them in the genome? We hypothesize that alterations
      in DNA methylation, an enzymatic covalent modification of cytosine bases in DNA,
      serve as a "genomic" memory of pain in the adult cortex. DNA methylation is an
      epigenetic mechanism for long-term regulation of gene expression. Neuronal
      plasticity at the neuroanatomical, functional, morphological, physiological and
      molecular levels has been demonstrated throughout the neuroaxis in response to
      persistent pain, including in the adult prefrontal cortex (PFC). We have
      previously reported widespread changes in gene expression and DNA methylation in
      the PFC many months following peripheral nerve injury. In support of this
      hypothesis, we show here that up-regulation of a gene involved with synaptic
      function, Synaptotagmin II (syt2), in the PFC in a chronic pain model is
      associated with long-term changes in DNA methylation. The challenges of
      understanding the contributions of epigenetic mechanisms such as DNA methylation
      within the PFC to pain chronicity and their therapeutic implications are
      discussed. 

PMID- 25852481
TI  - Differential modulation of repetitive firing and synchronous network activity in
      neocortical interneurons by inhibition of A-type K(+) channels and Ih.
AB  - GABAergic interneurons provide the main source of inhibition in the neocortex and
      are important in regulating neocortical network activity. In the presence 4
      aminopyridine (4-AP), CNQX, and D-APV, large amplitude GABAA-receptor mediated
      depolarizing responses were observed in the neocortex. GABAergic networks are
      comprised of several types of interneurons, each with its own protein expression
      pattern, firing properties, and inhibitory role in network activity. Voltage
      gated ion channels, especially A-type K(+) channels, differentially regulate
      passive membrane properties, action potential (AP) waveform, and repetitive
      firing properties in interneurons depending on their composition and
      localization. HCN channels are known modulators of pyramidal cell intrinsic
      excitability and excitatory network activity. Little information is available
      regarding how HCN channels functionally modulate excitability of individual
      interneurons and inhibitory networks. In this study, we examined the effect of 4
      AP on intrinsic excitability of fast-spiking basket cells (FS-BCs) and Martinotti
      cells (MCs). 4-AP increased the duration of APs in both FS-BCs and MCs. The
      repetitive firing properties of MCs were differentially affected compared to FS
      BCs. We also examined the effect of Ih inhibition on synchronous GABAergic
      depolarizations and synaptic integration of depolarizing IPSPs. ZD 7288 enhanced
      the amplitude and area of evoked GABAergic responses in both cell types.
      Similarly, the frequency and area of spontaneous GABAergic depolarizations in
      both FS-BCs and MCs were increased in presence of ZD 7288. Synaptic integration
      of IPSPs in MCs was significantly enhanced, but remained unaltered in FS-BCs.
      These results indicate that 4-AP differentially alters the firing properties of
      interneurons, suggesting MCs and FS-BCs may have unique roles in GABAergic
      network synchronization. Enhancement of GABAergic network synchronization by ZD
      7288 suggests that HCN channels attenuate inhibitory network activity. 

PMID- 25852483
TI  - Dendritic patch-clamp recordings from cerebellar granule cells demonstrate
      electrotonic compactness.
AB  - Cerebellar granule cells (GCs), the smallest neurons in the brain, have on
      average four short dendrites that receive high-frequency mossy fiber inputs
      conveying sensory information. The short length of the dendrites suggests that
      GCs are electrotonically compact allowing unfiltered integration of dendritic
      inputs. The small average diameter of the dendrites (~0.7 um), however, argues
      for dendritic filtering. Previous studies based on somatic recordings and
      modeling indicated that GCs are electrotonically extremely compact. Here, we
      performed patch-clamp recordings from GC dendrites in acute brain slices of mice
      to directly analyze the electrotonic properties of GCs. Strikingly, the input
      resistance did not differ significantly between dendrites and somata of GCs.
      Furthermore, spontaneous excitatory postsynaptic potentials (EPSP) were similar
      in amplitude at dendritic and somatic recording sites. From the dendritic and
      somatic input resistances we determined parameters characterizing the
      electrotonic compactness of GCs. These data directly demonstrate that cerebellar
      GCs are electrotonically compact and thus ideally suited for efficient high
      frequency information transfer. 

PMID- 25852484
TI  - Shank3-mutant mice lacking exon 9 show altered excitation/inhibition balance,
      enhanced rearing, and spatial memory deficit.
AB  - Shank3 is a postsynaptic scaffolding protein implicated in synapse development
      and autism spectrum disorders. The Shank3 gene is known to produce diverse splice
      variants whose functions have not been fully explored. In the present study, we
      generated mice lacking Shank3 exon 9 (Shank3 (Delta9) mice), and thus missing
      five out of 10 known Shank3 splice variants containing the N-terminal ankyrin
      repeat region, including the longest splice variant, Shank3a. Our X-gal staining
      results revealed that Shank3 proteins encoded by exon 9-containing splice
      variants are abundant in upper cortical layers, striatum, hippocampus, and
      thalamus, but not in the olfactory bulb or cerebellum, despite the significant
      Shank3 mRNA levels in these regions. The hippocampal CA1 region of Shank3
      (Delta9) mice exhibited reduced excitatory transmission at Schaffer collateral
      synapses and increased frequency of spontaneous inhibitory synaptic events in
      pyramidal neurons. In contrast, prelimbic layer 2/3 pyramidal neurons in the
      medial prefrontal cortex displayed decreased frequency of spontaneous inhibitory
      synaptic events, indicating alterations in the ratio of excitation/inhibition
      (E/I ratio) in the Shank3 (Delta9) brain. These mice displayed a mild increase in
      rearing in a novel environment and mildly impaired spatial memory, but showed
      normal social interaction and repetitive behavior. These results suggest that
      ankyrin repeat-containing Shank3 splice variants are important for E/I balance,
      rearing behavior, and spatial memory. 

PMID- 25852482
TI  - Researching glutamate - induced cytotoxicity in different cell lines: a
      comparative/collective analysis/study.
AB  - Although glutamate is one of the most important excitatory neurotransmitters of
      the central nervous system, its excessive extracellular concentration leads to
      uncontrolled continuous depolarization of neurons, a toxic process called,
      excitotoxicity. In excitotoxicity glutamate triggers the rise of intracellular
      Ca(2+) levels, followed by up regulation of nNOS, dysfunction of mitochondria,
      ROS production, ER stress, and release of lysosomal enzymes. Excessive calcium
      concentration is the key mediator of glutamate toxicity through over activation
      of ionotropic and metabotropic receptors. In addition, glutamate accumulation can
      also inhibit cystine (CySS) uptake by reversing the action of the CySS/glutamate
      antiporter. Reversal of the antiporter action reinforces the aforementioned
      events by depleting neurons of cysteine and eventually glutathione's reducing
      potential. Various cell lines have been employed in the pursuit to understand the
      mechanism(s) by which excitotoxicity affects the cells leading them ultimately to
      their demise. In some cell lines glutamate toxicity is exerted mainly through
      over activation of NMDA, AMPA, or kainate receptors whereas in other cell lines
      lacking such receptors, the toxicity is due to glutamate induced oxidative
      stress. However, in the greatest majority of the cell lines ionotropic glutamate
      receptors are present, co-existing to CySS/glutamate antiporters and metabotropic
      glutamate receptors, supporting the assumption that excitotoxicity effect in
      these cells is accumulative. Different cell lines differ in their responses when
      exposed to glutamate. In this review article the responses of PC12, SH-SY5Y, HT
      22, NT-2, OLCs, C6, primary rat cortical neurons, RGC-5, and SCN2.2 cell systems
      are systematically collected and analyzed. 

PMID- 25852485
TI  - Imbalance of excitation and inhibition at threshold level in the auditory cortex.
AB  - The interplay of cortical excitation and inhibition is a fundamental feature of
      cortical information processing. Excitation and inhibition in single cortical
      neurons are balanced in their response to optimal sensory stimulation due to
      thalamocortical feedforward microcircuitry. It is unclear whether the balance
      between cortical excitation and inhibition is maintained at the threshold
      stimulus level. Using in vivo whole-cell patch-clamp recording of thalamocortical
      recipient neurons in the primary auditory cortex of mice, we examined the tone
      evoked excitatory and inhibitory postsynaptic currents at threshold levels.
      Similar to previous reports, tone induced excitatory postsynaptic currents when
      the membrane potentials were held at 70 mV and inhibitory postsynaptic currents
      when the membrane potentials were held at 0 mV on single cortical neurons. This
      coupled excitation and inhibition is not demonstrated when threshold-level tone
      stimuli are presented. In most cases, tone induced only excitatory postsynaptic
      current. The best frequencies of excitatory and inhibitory responses were often
      different and thresholds of inhibitory responses were mostly higher than those of
      excitatory responses. Our data suggest that the excitatory and inhibitory inputs
      to single cortical neurons are imbalanced at the threshold level. This imbalance
      may result from the inherent dynamics of thalamocortical feedforward
      microcircuitry. 

PMID- 25852486
TI  - Glycine and GABAA receptors mediate tonic and phasic inhibitory processes that
      contribute to prepulse inhibition in the goldfish startle network.
AB  - Prepulse inhibition (PPI) is understood as a sensorimotor gating process that
      attenuates sensory flow to the startle pathway during early stages (20-1000 ms)
      of information processing. Here, we applied in vivo electrophysiology and
      pharmacology to determine if PPI is mediated by glycine receptors (GlyRs) and/or
      GABAA receptors (GABAARs) in the goldfish auditory startle circuit. Specifically,
      we used selective antagonists to dissect the contributions of target receptors on
      sound-evoked postsynaptic potentials (PSPs) recorded in the neurons that initiate
      startle, the Mauthner-cells (M-cell). We found that strychnine, a GlyR
      antagonist, disrupted a fast-activated (5 ms) and rapidly (<50 ms) decaying (feed
      forward) inhibitory process that contributes to PPI at 20 ms prepulse/pulse inter
      stimulus intervals (ISI). Additionally we observed increases of the evoked
      postsynaptic potential (PSP) peak amplitude (+87.43 +/- 21.53%, N = 9) and
      duration (+204 +/- 48.91%, N = 9). In contrast, treatment with bicuculline, a
      GABAAR antagonist, caused a general reduction in PPI across all tested
      interstimulus intervals (ISIs) (20-500 ms). Bicuculline also increased PSP peak
      amplitude (+133.8 +/- 10.3%, N = 5) and PSP duration (+284.95 +/- 65.64%, N = 5).
      Treatment with either antagonist also tonically increased post-synaptic
      excitability in the M-cells, reflected by an increase in the magnitude of
      antidromically-evoked action potentials (APs) by 15.07 +/- 3.21%, N = 7 and 16.23
      +/- 7.08%, N = 5 for strychnine and bicuculline, respectively. These results
      suggest that GABAARs and GlyRs are functionally segregated to short- and longer
      lasting sound-evoked (phasic) inhibitory processes that contribute to PPI, with
      the mediation of tonic inhibition by both receptor systems being critical for
      gain control within the M-cell startle circuit. 

PMID- 25852487
TI  - Exciting times for inhibition: GABAergic synaptic transmission in dentate gyrus
      interneuron networks.

PMID- 25852488
TI  - Localization of mutant ubiquitin in the brain of a transgenic mouse line with
      proteasomal inhibition and its validation at specific sites in Alzheimer's
      disease.
AB  - Loss of protein quality control by the ubiquitin-proteasome system (UPS) during
      aging is one of the processes putatively contributing to cellular stress and
      Alzheimer's disease (AD) pathogenesis. Recently, pooled Genome Wide Association
      Studies (GWAS), pathway analysis and proteomics identified protein ubiquitination
      as one of the key modulators of AD. Mutations in ubiquitin B mRNA that result in
      UBB(+1) dose-dependently cause an impaired UPS, subsequent accumulation of
      UBB(+1) and most probably depositions of other aberrant proteins present in
      plaques and neurofibrillary tangles. We used specific immunohistochemical probes
      for a comprehensive topographic mapping of the UBB(+1) distribution in the brains
      of transgenic mouse line 3413 overexpressing UBB(+1). We also mapped the
      expression of UBB(+1) in brain areas of AD patients selected based upon the
      distribution of UBB(+1) in line 3413. Therefore, we focused on the olfactory
      bulb, basal ganglia, nucleus basalis of Meynert, inferior colliculus and raphe
      nuclei. UBB(+1) distribution was compared with established probes for pre-tangles
      and tangles and Abeta plaques. UBB(+1) distribution found in line 3413 is partly
      mirrored in the AD brain. Specifically, nuclei with substantial accumulations of
      tangle-bearing neurons, such as the nucleus basalis of Meynert and raphe nuclei
      also present high densities of UBB(+1) positive tangles. Line 3413 is useful for
      studying the contribution of proteasomal dysfunction in AD. The findings are
      consistent with evidence that areas outside the forebrain are also affected in
      AD. Line 3413 may also be predictive for other conformational diseases, including
      related tauopathies and polyglutamine diseases, in which UBB(+1) accumulates in
      their cellular hallmarks. 

PMID- 25852489
TI  - A new scenario of hypothalamic organization: rationale of new hypotheses
      introduced in the updated prosomeric model.
AB  - In this essay, we aim to explore in depth the new concept of the hypothalamus
      that was presented in the updated prosomeric model (Puelles et al., 2012b; Allen
      Developing Mouse Brain Atlas). Initial sections deal with the antecedents of
      prosomeric ideas represented by the extensive literature centered on the
      alternative columnar model of Herrick (1910), Kuhlenbeck (1973) and Swanson
      (1992, 2003); a detailed critique explores why the columnar model is not helpful
      in the search for causal developmental explanations. In contrast, the emerging
      prosomeric scenario visibly includes many possibilities to propose causal
      explanations of hypothalamic structure relative to both anteroposterior and
      dorsoventral patterning mechanisms, and insures the possibility to compare
      hypothalamic histogenesis with that of more caudal parts of the brain. Next the
      four major changes introduced in the organization of the hypothalamus on occasion
      of the updated model are presented, and our rationale for these changes is
      explored in detail. It is hoped that this example of morphological theoretical
      analysis may be useful for readers interested in brain models, or in
      understanding why models may need to change in the quest for higher consistency. 

PMID- 25852490
TI  - Synaptic connectivity of the cholinergic axons in the olfactory bulb of the
      cynomolgus monkey.
AB  - The olfactory bulb (OB) of mammals receives cholinergic afferents from the
      horizontal limb of the diagonal band of Broca (HDB). At present, the synaptic
      connectivity of the cholinergic axons on the circuits of the OB has only been
      investigated in the rat. In this report, we analyze the synaptic connectivity of
      the cholinergic axons in the OB of the cynomolgus monkey (Macaca fascicularis).
      Our aim is to investigate whether the cholinergic innervation of the bulbar
      circuits is phylogenetically conserved between macrosmatic and microsmatic
      mammals. Our results demonstrate that the cholinergic axons form synaptic
      contacts on interneurons. In the glomerular layer, their main targets are the
      periglomerular cells, which receive axo-somatic and axo-dendritic synapses. In
      the inframitral region, their main targets are the granule cells, which receive
      synaptic contacts on their dendritic shafts and spines. Although the cholinergic
      boutons were frequently found in close vicinity of the dendrites of principal
      cells, we have not found synaptic contacts on them. From a comparative
      perspective, our data indicate that the synaptic connectivity of the cholinergic
      circuits is highly preserved in the OB of macrosmatic and microsmatic mammals. 

PMID- 25852492
TI  - The nasal cavity and its olfactory sensory territories.

PMID- 25852491
TI  - Cadherins mediate sequential roles through a hierarchy of mechanisms in the
      developing mammillary body.
AB  - Expression of intricate combinations of cadherins (a family of adhesive membrane
      proteins) is common in the developing central nervous system. On this basis, a
      combinatorial cadherin code has long been proposed to underlie neuronal sorting
      and to be ultimately responsible for the layers, columns and nuclei of the brain.
      However, experimental proof of this particular function of cadherins has proven
      difficult to obtain and the question is still not clear. Alternatively, non
      specific, non-combinatorial, purely quantitative adhesive differentials have been
      proposed to explain neuronal sorting in the brain. Do cadherin combinations
      underlie brain cytoarchitecture? We approached this question using as model a
      well-defined forebrain nucleus, the mammillary body (MBO), which shows strong,
      homogeneous expression of one single cadherin (Cdh11) and patterned,
      combinatorial expression of Cdh6, -8 and -10. We found that, besides the known
      combinatorial Cdh pattern, MBO cells are organized into a second, non-overlapping
      pattern grouping neurons with the same date of neurogenesis. We report that, in
      the Foxb1 mouse mutant, Cdh11 expression fails to be maintained during MBO
      development. This disrupted the combination-based as well as the birthdate-based
      sorting in the mutant MBO. In utero RNA interference (RNAi) experiments knocking
      down Cdh11 in MBO-fated migrating neurons at one specific age showed that Cdh11
      expression is required for chronological entrance in the MBO. Our results suggest
      that neuronal sorting in the developing MBO is caused by adhesion-based, non
      combinatorial mechanisms that keep neurons sorted according to birthdate
      information (possibly matching them to target neurons chronologically sorted in
      the same manner). Non-specific adhesion mechanisms would also prevent cadherin
      combinations from altering the birthdate-based sorting. Cadherin combinations
      would presumably act later to support specific synaptogenesis through specific
      axonal fasciculation and final target recognition. 

PMID- 25852493
TI  - Acute oral administration of low doses of methylphenidate targets calretinin
      neurons in the rat septal area.
AB  - Methylphenidate (MPD) is a commonly administered drug to treat children suffering
      from attention deficit hyperactivity disorder (ADHD). Alterations in septal
      driven hippocampal theta rhythm may underlie attention deficits observed in these
      patients. Amongst others, the septo-hippocampal connections have long been
      acknowledged to be important in preserving hippocampal function. Thus, we wanted
      to ascertain if MPD administration, which improves attention in patients, could
      affect septal areas connecting with hippocampus. We used low and orally
      administered MPD doses (1.3, 2.7 and 5 mg/Kg) to rats what mimics the dosage
      range in humans. In our model, we observed no effect when using 1.3 mg/Kg MPD;
      whereas 2.7 and 5 mg/Kg induced a significant increase in c-fos expression
      specifically in the medial septum (MS), an area intimately connected to the
      hippocampus. We analyzed dopaminergic areas such as nucleus accumbens and
      striatum, and found that only 5 mg/Kg induced c-fos levels increase. In these
      areas tyrosine hydroxylase correlated well with c-fos staining, whereas in the MS
      the sparse tyrosine hydroxylase fibers did not overlap with c-fos positive
      neurons. Double immunofluorescence of c-fos with neuronal markers in the septal
      area revealed that co-localization with choline acethyl transferase, parvalbumin,
      and calbindin with c-fos did not change with MPD treatment; whereas, calretinin
      and c-fos double labeled neurons increased after MPD administration. Altogether,
      these results suggest that low and acute doses of methylphenidate primary target
      specific populations of caltretinin medial septal neurons. 

PMID- 25852494
TI  - Remotely-supervised transcranial direct current stimulation (tDCS) for clinical
      trials: guidelines for technology and protocols.
AB  - The effect of transcranial direct current stimulation (tDCS) is cumulative.
      Treatment protocols typically require multiple consecutive sessions spanning
      weeks or months. However, traveling to clinic for a tDCS session can present an
      obstacle to subjects and their caregivers. With modified devices and headgear,
      tDCS treatment can be administered remotely under clinical supervision,
      potentially enhancing recruitment, throughput, and convenience. Here we propose
      standards and protocols for clinical trials utilizing remotely-supervised tDCS
      with the goal of providing safe, reproducible and well-tolerated stimulation
      therapy outside of the clinic. The recommendations include: (1) training of staff
      in tDCS treatment and supervision; (2) assessment of the user's capability to
      participate in tDCS remotely; (3) ongoing training procedures and materials
      including assessments of the user and/or caregiver; (4) simple and fail-safe
      electrode preparation techniques and tDCS headgear; (5) strict dose control for
      each session; (6) ongoing monitoring to quantify compliance (device preparation,
      electrode saturation/placement, stimulation protocol), with corresponding
      corrective steps as required; (7) monitoring for treatment-emergent adverse
      effects; (8) guidelines for discontinuation of a session and/or study
      participation including emergency failsafe procedures tailored to the treatment
      population's level of need. These guidelines are intended to provide a minimal
      level of methodological rigor for clinical trials seeking to apply tDCS outside a
      specialized treatment center. We outline indication-specific applications
      (Attention Deficit Hyperactivity Disorder, Depression, Multiple Sclerosis,
      Palliative Care) following these recommendations that support a standardized
      framework for evaluating the tolerability and reproducibility of remote
      supervised tDCS that, once established, will allow for translation of tDCS
      clinical trials to a greater size and range of patient populations. 

PMID- 25852495
TI  - Modulating pathological oscillations by rhythmic non-invasive brain stimulation-a
      therapeutic concept?
AB  - A large amount of studies of the last decades revealed an association between
      human behavior and oscillatory activity in the human brain. Alike, abnormalities
      of oscillatory activity were related with pathological behavior in many
      neuropsychiatric disorders, such as in Parkinson's disease (PD) or in
      schizophrenia (SCZ). As a therapeutic tool, non-invasive brain stimulation (NIBS)
      has demonstrated the potential to improve behavioral performance in patients
      suffering from neuropsychiatric disorders. Since evidence accumulates that NIBS
      might be able to modulate oscillatory activity and related behavior in a
      scientific setting, this review focuses on discussing potential interventional
      strategies to target abnormalities in oscillatory activity in neuropsychiatric
      disorders. In particular, we will review oscillatory changes described in
      patients after stroke, with PD or suffering from SCZ. Potential ways of targeting
      interventionally the underlying pathological oscillations to improve related
      pathological behavior will be further discussed. 

PMID- 25852497
TI  - A new measure for the revised reinforcement sensitivity theory: psychometric
      criteria and genetic validation.
AB  - Jeffrey Gray's Reinforcement Sensitivity Theory (RST) represents one of the most
      influential biologically-based personality theories describing individual
      differences in approach and avoidance tendencies. The most prominent self-report
      inventory to measure individual differences in approach and avoidance behavior to
      date is the BIS/BAS scale by Carver and White (1994). As Gray and McNaughton
      (2000) revised the RST after its initial formulation in the 1970/80s, and given
      the Carver and White measure is based on the initial conceptualization of RST,
      there is a growing need for self-report inventories measuring individual
      differences in the revised behavioral inhibition system (BIS), behavioral
      activation system (BAS) and the fight, flight, freezing system (FFFS). Therefore,
      in this paper we present a new questionnaire measuring individual differences in
      the revised constructs of the BIS, BAS and FFFS in N = 1814 participants (German
      sample). An English translated version of the new measure is also presented and
      tested in N = 299 English language participants. A large number of German
      participants (N = 1090) also filled in the BIS/BAS scales by Carver and White
      (1994) and the correlations between these measures are presented. Finally, this
      same subgroup of participants provided buccal swaps for the investigation of the
      arginine vasopressin receptor 1a (AVPR1a) gene. Here, a functional genetic
      polymorphism (rs11174811) on the AVPR1a gene was shown to be associated with
      individual differences in both the revised BIS and classic BIS dimensions. 

PMID- 25852498
TI  - The cognitive thalamus.

PMID- 25852496
TI  - Theta variation and spatiotemporal scaling along the septotemporal axis of the
      hippocampus.
AB  - Hippocampal theta has been related to locomotor speed, attention, anxiety,
      sensorimotor integration and memory among other emergent phenomena. One
      difficulty in understanding the function of theta is that the hippocampus (HPC)
      modulates voluntary behavior at the same time that it processes sensory input.
      Both functions are correlated with characteristic changes in theta indices. The
      current review highlights a series of studies examining theta local field
      potential (LFP) signals across the septotemporal or longitudinal axis of the HPC.
      While the theta signal is coherent throughout the entirety of the HPC, the
      amplitude, but not the frequency, of theta varies significantly across its three
      dimensional expanse. We suggest that the theta signal offers a rich vein of
      information about how distributed neuronal ensembles support emergent function.
      Further, we speculate that emergent function across the long axis varies with
      respect to spatiotemporal scale. Thus, septal HPC processes details of the
      proximal spatiotemporal environment while more temporal aspects process larger
      spaces and wider time-scales. The degree to which emergent functions are
      supported by the synchronization of theta across the septotemporal axis is an
      open question. Our working model is that theta synchrony serves to bind ensembles
      representing varying resolutions of spatiotemporal information at interdependent
      septotemporal areas of the HPC. Such synchrony and cooperative interactions along
      the septotemporal axis likely support memory formation and subsequent
      consolidation and retrieval. 

PMID- 25852499
TI  - A pavlovian model of the amygdala and its influence within the medial temporal
      lobe.
AB  - Recent advances in neuroscience give us a better view of the inner structure of
      the amygdala, of its relations with other regions in the Medial Temporal Lobe
      (MTL) and of the prominent role of neuromodulation. They have particularly shed
      light on two kinds of neurons in the basal nucleus of the amygdala, the so-called
      fear neurons and extinction neurons. Fear neurons mediate context-dependent fear
      by receiving contextual information from the hippocampus, whereas extinction
      neurons are linked with the medial prefrontal cortex (mPFC) and involved in fear
      extinction. The computational model of the amygdala that we describe in this
      paper is primarily a model of pavlovian conditioning, but its architecture also
      emphasizes the central role of the amygdala in the MTL memory processes through
      three main information flows. (i) Thalamic and higher order sensory cortical
      inputs including from the perirhinal cortex are received in the lateral amygdalar
      nucleus, where CS-US associations can be acquired. (ii) These associations are
      subsequently modulated, in the basal nucleus of the amygdala, by contextual
      inputs coming from the hippocampus and the mPFC. Basal fear and extinction
      neurons indicate the currently valid association to their main targets including
      in the MTL and the mPFC. (iii) The competition for the choice of the pavlovian
      response is ultimately performed by projection of these amygdalar neurons in the
      central nucleus of the amygdala where, beyond motor responding, a hormonal
      response, including cholinergic modulation, is also triggered via the basal
      forebrain. In turn, acetylcholine modulates activation in the basal nucleus and
      facilitates learning in the hippocampus. Based on biologically founded arguments,
      our model replicates a number of biological experiments, proposes some
      predictions about the role of amygdalar regions and describes pavlovian
      conditioning as a distributed systemic learning, binding memory processes in the
      MTL. 

PMID- 25852501
TI  - Editorial for research topic "Autism: the movement perspective".

PMID- 25852500
TI  - Individual differences in approach-avoidance aptitude: some clues from research
      on Parkinson's disease.
AB  - Approach and avoidance are two basic behavioral aptitudes of humans whose correct
      balance is critical for successful adaptation to the environment. As the
      expression of approach and avoidance tendencies may differ significantly between
      healthy individuals, different psychobiological factors have been posited to
      account for such variability. In this regard, two main issues are still open that
      refers to (i) the role played by dopamine neurotransmission; and (ii) the
      possible influence of cognitive characteristics, particularly executive
      functioning. The aim of the present paper was to highlight the contribution of
      research on Parkinson's disease (PD) to our understanding of the above issues. In
      particular, we here reviewed PD literature to clarify whether neurobiological and
      neuropsychological modifications due to PD are associated to changes in approach
      avoidance related personality features. Available data indicate that PD patients
      may show and approach-avoidance imbalance as documented by lower novelty-seeking
      and higher harm-avoidance behaviors, possibly suggesting a relationship with
      neurobiological and neurocognitive PD-related changes. However, the literature
      that directly investigated this issue is still sparse and much more work is
      needed to better clarify it. 

PMID- 25852503
TI  - Commentary on: An exploration of sensory and movement differences from the
      perspective of individuals with autism.

PMID- 25852502
TI  - The addicted brain: understanding the neurophysiological mechanisms of addictive
      disorders.

PMID- 25852504
TI  - Neuromodulation and the mind-brain relation.

PMID- 25852505
TI  - Perception of biological motion from size-invariant body representations.
AB  - The visual recognition of action is one of the socially most important and
      computationally demanding capacities of the human visual system. It combines
      visual shape recognition with complex non-rigid motion perception. Action
      presented as a point-light animation is a striking visual experience for anyone
      who sees it for the first time. Information about the shape and posture of the
      human body is sparse in point-light animations, but it is essential for action
      recognition. In the posturo-temporal filter model of biological motion perception
      posture information is picked up by visual neurons tuned to the form of the human
      body before body motion is calculated. We tested whether point-light stimuli are
      processed through posture recognition of the human body form by using a typical
      feature of form recognition, namely size invariance. We constructed a point-light
      stimulus that can only be perceived through a size-invariant mechanism. This
      stimulus changes rapidly in size from one image to the next. It thus disrupts
      continuity of early visuo-spatial properties but maintains continuity of the body
      posture representation. Despite this massive manipulation at the visuo-spatial
      level, size-changing point-light figures are spontaneously recognized by naive
      observers, and support discrimination of human body motion. 

PMID- 25852506
TI  - Impact of an additional chronic BDNF reduction on learning performance in an
      Alzheimer mouse model.
AB  - There is increasing evidence that brain-derived neurotrophic factor (BDNF) plays
      a crucial role in Alzheimer's disease (AD) pathology. A number of studies
      demonstrated that AD patients exhibit reduced BDNF levels in the brain and the
      blood serum, and in addition, several animal-based studies indicated a potential
      protective effect of BDNF against Abeta-induced neurotoxicity. In order to
      further investigate the role of BDNF in the etiology of AD, we created a novel
      mouse model by crossing a well-established AD mouse model (APP/PS1) with a mouse
      exhibiting a chronic BDNF deficiency (BDNF(+/-)). This new triple transgenic
      mouse model enabled us to further analyze the role of BDNF in AD in vivo. We
      reasoned that in case BDNF has a protective effect against AD pathology, an AD
      like phenotype in our new mouse model should occur earlier and/or in more
      severity than in the APP/PS1-mice. Indeed, the behavioral analysis revealed that
      the APP/PS1-BDNF(+/-)-mice show an earlier onset of learning impairments in a two
      way active avoidance task in comparison to APP/PS1- and BDNF(+/-)-mice. However
      in the Morris water maze (MWM) test, we could not observe an overall aggrevated
      impairment in spatial learning and also short-term memory in an object
      recognition task remained intact in all tested mouse lines. In addition to the
      behavioral experiments, we analyzed the amyloid plaque pathology in the APP/PS1
      and APP/PS1-BDNF(+/-)-mice and observed a comparable plaque density in the two
      genotypes. Moreover, our results revealed a higher plaque density in prefrontal
      cortical compared to hippocampal brain regions. Our data reveal that higher
      cognitive tasks requiring the recruitment of cortical networks appear to be more
      severely affected in our new mouse model than learning tasks requiring mainly sub
      cortical networks. Furthermore, our observations of an accelerated impairment in
      active avoidance learning in APP/PS1-BDNF(+/-)-mice further supports the
      hypothesis that BDNF deficiency amplifies AD-related cognitive dysfunctions. 

PMID- 25852507
TI  - The alteration of gray matter volume and cognitive control in adolescents with
      internet gaming disorder.
AB  - OBJECTIVE: Internet gaming disorder (IGD) has been investigated by many
      behavioral and neuroimaging studies, for it has became one of the main behavior
      disorders among adolescents. However, few studies focused on the relationship
      between alteration of gray matter volume (GMV) and cognitive control feature in
      IGD adolescents. METHODS: Twenty-eight participants with IAD and twenty-eight
      healthy age and gender matched controls participated in the study. Brain
      morphology of adolescents with IGD and healthy controls was investigated using an
      optimized voxel-based morphometry (VBM) technique. Cognitive control performances
      were measured by Stroop task, and correlation analysis was performed between
      brain structural change and behavioral performance in IGD group. RESULTS: The
      results showed that GMV of the bilateral anterior cingulate cortex (ACC),
      precuneus, supplementary motor area (SMA), superior parietal cortex, left dorsal
      lateral prefrontal cortex (DLPFC), left insula, and bilateral cerebellum
      decreased in the IGD participants compared with healthy controls. Moreover, GMV
      of the ACC was negatively correlated with the incongruent response errors of
      Stroop task in IGD group. CONCLUSION: Our results suggest that the alteration of
      GMV is associated with the performance change of cognitive control in adolescents
      with IGD, which indicating substantial brain image effects induced by IGD.

PMID- 25852508
TI  - Glycogen synthase kinase-3beta inhibition in the medial prefrontal cortex
      mediates paradoxical amphetamine action in a mouse model of ADHD.
AB  - Psychostimulants show therapeutic efficacy in the treatment of attention-deficit
      hyperactivity disorder (ADHD). It is generally assumed that they ameliorate ADHD
      symptoms via interfering with monoaminergic signaling. We combined behavioral
      pharmacology, neurochemistry and molecular analyses to identify mechanisms
      underlying the paradoxical calming effect of amphetamine in low trait anxiety
      behavior (LAB) mice, a novel multigenetic animal model of ADHD. Amphetamine (1
      mg/kg) and methylphenidate (10 mg/kg) elicited similar dopamine and
      norepinephrine release in the medial prefrontal cortex (mPFC) and in the striatum
      of LAB mice. In contrast, amphetamine decreased, while methylphenidate increased
      locomotor activity. This argues against changes in dopamine and/or norepinephrine
      release as mediators of amphetamine paradoxical effects. Instead, the calming
      activity of amphetamine corresponded to the inhibition of glycogen synthase
      kinase 3beta (GSK3beta) activity, specifically in the mPFC. Accordingly, not only
      systemic administration of the GSK3beta inhibitor TDZD-8 (20 mg/kg), but also
      local microinjections of TDZD-8 and amphetamine into the mPFC, but not into the
      striatum, decreased locomotor activity in LAB mice. Amphetamine effects seem to
      depend on NMDA receptor signaling, since pre- or co-treatment with MK-801 (0.3
      mg/kg) abolished the effects of amphetamine (1 mg/kg) on the locomotion and on
      the phosphorylation of GSK3beta at the level of the mPFC. Taken together, the
      paradoxical calming effect of amphetamine in hyperactive LAB mice concurs with a
      decreased GSK3beta activity in the mPFC. This effect appears to be independent of
      dopamine or norepinephrine release, but contingent on NMDA receptor signaling. 

PMID- 25852509
TI  - Can electrical stimulation of the human bed nucleus of the stria terminalis
      reduce contextual anxiety? An unanswered question.

PMID- 25852510
TI  - Binding in working memory and frontal lobe in normal aging: is there any
      similarity with autism?
AB  - Some studies highlight similarities between Autism Spectrum Disorder (ASD) and
      healthy aging. Indeed, the decline in older individuals' ability to create a
      unified representation of the individual features of an event is thought to arise
      from a disruption of binding within the episodic buffer of working memory (WM) as
      the same way as observed in ASD. In both cases, this deficit may result from an
      abnormal engagement of a frontohippocampal network. The objective of the present
      study is to identify both cognitive processes and neural substrates associated
      with the deficit of binding in WM in healthy aging. We studied the capacity of
      binding and the cognitive processes that might subtend its decline in 72 healthy
      participants aged 18-84 years. We examined the behavioral data in relation to the
      changes in brain metabolism associated with the age-related decline in a subgroup
      of 34 healthy participants aged 20-77 years using the resting-state [(18)F]
      fluorodeoxyglucose positron emission tomography ((18)F-FDG PET). Forward stepwise
      regression analyses showed that the age-related decline in binding was partially
      explained by a decline in inhibition and processing speed. PET correlation
      analyses indicated that metabolism of the frontal regions, anterior and middle
      cingulate cortices is implicated in this phenomenon. These data suggest that
      executive functions and processing speed may play a crucial role in the capacity
      to integrate unified representations in memory in aging. Possible implications
      are discussed in ASD. 

PMID- 25852511
TI  - Altered baseline brain activity in experts measured by amplitude of low frequency
      fluctuations (ALFF): a resting state fMRI study using expertise model of
      acupuncturists.
AB  - It is well established that expertise modulates evoked brain activity in response
      to specific stimuli. Recently, researchers have begun to investigate how
      expertise influences the resting brain. Among these studies, most focused on the
      connectivity features within/across regions, i.e., connectivity
      patterns/strength. However, little concern has been given to a more fundamental
      issue whether or not expertise modulates baseline brain activity. We investigated
      this question using amplitude of low-frequency (<0.08 Hz) fluctuation (ALFF) as
      the metric of brain activity and a novel expertise model, i.e., acupuncturists,
      due to their robust proficiency in tactile perception and emotion regulation.
      After the psychophysical and behavioral expertise screening procedure, 23
      acupuncturists and 23 matched non-acupuncturists (NA) were enrolled. Our results
      explicated higher ALFF for acupuncturists in the left ventral medial prefrontal
      cortex (VMPFC) and the contralateral hand representation of the primary
      somatosensory area (SI) (corrected for multiple comparisons). Additionally, ALFF
      of VMPFC was negatively correlated with the outcomes of the emotion regulation
      task (corrected for multiple comparisons). We suggest that our study may reveal a
      novel connection between the neuroplasticity mechanism and resting state
      activity, which would upgrade our understanding of the central mechanism of
      learning. Furthermore, by showing that expertise can affect the baseline brain
      activity as indicated by ALFF, our findings may have profound implication for
      functional neuroimaging studies especially those involving expert models, in that
      difference in baseline brain activity may either smear the spatial pattern of
      activations for task data or introduce biased results into connectivity-based
      analysis for resting data. 

PMID- 25852512
TI  - Must analysis of meaning follow analysis of form? A time course analysis.
AB  - Many models of word recognition assume that processing proceeds sequentially from
      analysis of form to analysis of meaning. In the context of morphological
      processing, this implies that morphemes are processed as units of form prior to
      any influence of their meanings. Some interpret the apparent absence of
      differences in recognition latencies to targets (SNEAK) in form and semantically
      similar (sneaky-SNEAK) and in form similar and semantically dissimilar (sneaker
      SNEAK) prime contexts at a stimulus onset asynchrony (SOA) of 48 ms as consistent
      with this claim. To determine the time course over which degree of semantic
      similarity between morphologically structured primes and their targets influences
      recognition in the forward masked priming variant of the lexical decision
      paradigm, we compared facilitation for the same targets after semantically
      similar and dissimilar primes across a range of SOAs (34-100 ms). The effect of
      shared semantics on recognition latency increased linearly with SOA when long
      SOAs were intermixed (Experiments 1A and 1B) and latencies were significantly
      faster after semantically similar than dissimilar primes at homogeneous SOAs of
      48 ms (Experiment 2) and 34 ms (Experiment 3). Results limit the scope of form
      then-semantics models of recognition and demonstrate that semantics influences
      even the very early stages of recognition. Finally, once general performance
      across trials has been accounted for, we fail to provide evidence for individual
      differences in morphological processing that can be linked to measures of reading
      proficiency. 

PMID- 25852513
TI  - Transcranial direct current stimulation modulates efficiency of reading
      processes.
AB  - Transcranial direct current stimulation (tDCS) is a neuromodulatory technique
      that offers promise as an investigative method for understanding complex
      cognitive operations such as reading. This study explores the ability of a single
      session of tDCS to modulate reading efficiency and phonological processing
      performance within a group of healthy adults. Half the group received anodal or
      cathodal stimulation, on two separate days, of the left temporo-parietal junction
      while the other half received anodal or cathodal stimulation of the right
      homologue area. Pre- and post-stimulation assessment of reading efficiency and
      phonological processing was carried out. A larger pre-post difference in reading
      efficiency was found for participants who received right anodal stimulation
      compared to participants who received left anodal stimulation. Further, there was
      a significant post-stimulation increase in phonological processing speed
      following right hemisphere anodal stimulation. Implications for models of reading
      and reading impairment are discussed. 

PMID- 25852514
TI  - Similarity hypothesis: understanding of others with autism spectrum disorders by
      individuals with autism spectrum disorders.
AB  - Individuals with an autism spectrum disorder (ASD) are generally thought to lack
      empathy. However, according to recent empirical and self-advocacy studies,
      individuals with ASD identify with others with ASD. Based on mutual
      understanding, individuals with ASD respond empathically to others with these
      disorders. Results have shown that typically developing (TD) adults identify with
      TD fictional characters, and that such identification plays a critical role in
      social cognition. TD individuals retrieve episodes involving TD individuals
      faster than they retrieve episodes involving ASD individuals. Individuals with
      ASD also show a "similarity effect" whereby they retrieve stories involving ASD
      individuals more effectively when the stories have consistent outcomes than when
      they have inconsistent outcomes. In this context, I hypothesized that
      similarities between a perceiver and a target facilitate cognitive processing.
      This hypothesis was named the "similarity hypothesis". Perceivers empathize with
      targets similar to themselves, which facilitates subsequent cognitive processing.
      Behavioral and neuroimaging studies are reviewed based on the similarity
      hypothesis. 

PMID- 25852516
TI  - Objective and personalized longitudinal assessment of a pregnant patient with
      post severe brain trauma.
AB  - BACKGROUND: Following severe trauma to the brain (whether internally generated by
      seizures, tumors or externally caused by collision with or penetration of
      objects) individuals may experience initial coma state followed by slow recovery
      and rehabilitation treatment. At present there is no objective biometric to track
      the daily progression of the person for extended periods of time. OBJECTIVE: We
      introduce new analytical techniques to process data from physically wearable
      sensors and help track the longitudinal progression of motions and physiological
      states upon the brain trauma. Setting and Participant: The data used to
      illustrate the methods were collected at the hospital settings from a pregnant
      patient in coma state. The patient had brain trauma from a large debilitating
      seizure due to a large tumor in the right pre-frontal lobe. MAIN MEASURES: We
      registered the wrist motions and the surface-skin-temperature across several
      daily sessions in four consecutive months. A new statistical technique is
      introduced for personalized analyses of the rates of change of the stochastic
      signatures of these patterns. RESULTS: We detected asymmetries in the wrists'
      data that identified in the dominant limb critical points of change in
      physiological and motor control states. These patterns could blindly identify the
      time preceding the baby's delivery by C-section when the patient systematically
      brought her hand to her abdominal area. Changes in temperature were sharp and
      accompanied by systematic changes in the statistics of the motions that rendered
      her dominant wrist's micro-movements more systematically reliable and predictable
      than those of the non-dominant writst. CONCLUSIONS: The new analytics paired with
      wearable sensing technology may help track the day-by-day individual progression
      of a patient with post brain trauma in clinical settings and in the home
      environment.

PMID- 25852515
TI  - Solving the detour problem in navigation: a model of prefrontal and hippocampal
      interactions.
AB  - Adapting behavior to accommodate changes in the environment is an important
      function of the nervous system. A universal problem for motile animals is the
      discovery that a learned route is blocked and a detour is required. Given the
      substantial neuroscience research on spatial navigation and decision-making it is
      surprising that so little is known about how the brain solves the detour problem.
      Here we review the limited number of relevant functional neuroimaging, single
      unit recording and lesion studies. We find that while the prefrontal cortex (PFC)
      consistently responds to detours, the hippocampus does not. Recent evidence
      suggests the hippocampus tracks information about the future path distance to the
      goal. Based on this evidence we postulate a conceptual model in which: Lateral
      PFC provides a prediction error signal about the change in the path, frontopolar
      and superior PFC support the re-formulation of the route plan as a novel subgoal
      and the hippocampus simulates the new path. More data will be required to
      validate this model and understand (1) how the system processes the different
      options; and (2) deals with situations where a new path becomes available (i.e.,
      shortcuts). 

PMID- 25852517
TI  - The social life of voices: studying the neural bases for the expression and
      perception of the self and others during spoken communication.

PMID- 25852518
TI  - A pilot study on the effect of cognitive training on BDNF serum levels in
      individuals with Parkinson's disease.
AB  - Parkinson's disease (PD) patients, besides motor dysfunctions, may also display
      mild cognitive deficits (MCI) which increase with disease progression. The
      neurotrophin brain-derived neurotrophic factor (BDNF) plays a role in the
      survival of dopaminergic neurons and in the regulation of synaptic connectivity.
      Moreover, the brain and peripheral level of this protein may be significantly
      reduced in PD patients. These data suggest that a cognitive rehabilitation
      protocol aimed at restoring cognitive deficits in PD patients may also involve
      changes in this neurotrophin. Thus, in this pilot study we evaluated the effect
      of a cognitive rehabilitation protocol focused on the training of executive
      functioning and measured BDNF serum levels in a group of PD patients with mild
      cognitive impairment, as compared to the effect of a placebo treatment (n = 7/8
      group). The results showed that PD patients undergoing the cognitive
      rehabilitation, besides improving their cognitive performance as measured with
      the Zoo Map Test, also displayed increased serum BDNF levels as compared to the
      placebo group. These findings suggest that BDNF serum levels may represent a
      biomarker of the effects of cognitive rehabilitation in PD patients affected by
      MCI. However, the functional significance of this increase in PD as well as other
      neuropathological conditions remains to be determined. 

PMID- 25852519
TI  - Plasma oxytocin explains individual differences in neural substrates of social
      perception.
AB  - The neuropeptide oxytocin plays a critical role in social cognition and behavior.
      A number of studies using intranasal administration have demonstrated that
      oxytocin improves social perception. However, little is known about the
      relationship between individual differences in endogenous levels of oxytocin and
      social cognition. In the current study, we assessed the relationship between
      endogenous oxytocin and brain activity during an animacy perception paradigm.
      Thirty-seven male participants underwent scanning and provided a blood sample for
      oxytocin analysis. In line with previous research, perception of animacy was
      associated with activations in superior temporal sulcus, inferior frontal gyrus,
      and medial prefrontal cortex (mPFC). Notably, participants' levels of plasma
      oxytocin robustly predicted activation in areas critical for social cognitive
      processes, such that higher oxytocin levels were related to increased activity in
      dorsal mPFC, ventral mPFC, dorsolateral PFC, superior temporal gyrus, and
      temporoparietal junction (TPJ), suggesting differential processing of social
      stimuli. Together these results show that stable variations in endogenous
      oxytocin levels explain individual differences in social perception. 

PMID- 25852522
TI  - A real-life illusion of assimilation in the human face: eye size illusion caused
      by eyebrows and eye shadow.
AB  - Does an assimilative illusion like the Delboeuf illusion occur in the human face?
      We investigated factors that might influence the perceived size of the eyes in a
      realistic face. Experiment 1 manipulated the position of the eyebrows (high or
      low), the presence/absence of eye shadow, and the viewing distance (0.6 m or 5
      m), then measured the perceived eye size using a psychophysical method. The
      results showed that low eyebrows (i.e., closer to the eyes) make the eyes appear
      larger, suggesting that the assimilation of eyes into the eyebrows is stronger
      when the eye-eyebrow distance is shorter. The results also demonstrated that the
      application of eye shadow also makes the eyes look larger. Moreover, the effect
      of eye shadow is more pronounced when viewed from a distance. In order to
      investigate the mechanism of the eye size illusion demonstrated in Experiment 1,
      Experiment 2 measured the magnitude of the Delboeuf illusion at a viewing
      distance of 0.6 m or 5 m, with or without gray gradation simulating the eye
      shadow that was used in Experiment 1. The experiment demonstrated that the
      Delboeuf illusion is modulated by viewing distance and gradation in the same way
      as the eye size illusion. These results suggest that the eye size illusion
      induced by the eyebrows and the Delboeuf illusion involve the same mechanism, and
      that eye shadow causes the assimilation of the eyes into itself and enhances
      assimilation between the eyes and the eyebrows. 

PMID- 25852521
TI  - Greater widespread functional connectivity of the caudate in older adults who
      practice kripalu yoga and vipassana meditation than in controls.
AB  - There has been a growing interest in understanding how contemplative practices
      affect brain functional organization. However, most studies have restricted their
      exploration to predefined networks. Furthermore, scientific comparisons of
      different contemplative traditions are largely lacking. Here we explored
      differences in whole brain resting state functional connectivity between
      experienced yoga practitioners, experienced meditators, and matched controls.
      Analyses were repeated in an independent sample of experienced meditators and
      matched controls. Analyses utilizing Network-Based Statistics (Zalesky et al.,
      2010) revealed difference components for yoga practitioners > controls and
      meditators > controls in which the right caudate was a central node. Follow up
      analyses revealed that yoga practitioners and meditators had significantly
      greater degree centrality in the caudate than controls. This greater degree
      centrality was not driven by single connections but by greater connectivity
      between the caudate and numerous brain regions. Findings of greater caudate
      connectivity in meditators than in controls was replicated in an independent
      dataset. These findings suggest that yoga and meditation practitioners have
      stronger functional connectivity within basal ganglia cortico-thalamic feedback
      loops than non-practitioners. Although we could not provide evidence for its
      mechanistic role, this greater connectivity might be related to the often
      reported effects of meditation and yoga on behavioral flexibility, mental health,
      and well-being. 

PMID- 25852520
TI  - Aberrant cerebellar connectivity in motor and association networks in
      schizophrenia.
AB  - Schizophrenia is a devastating illness characterized by disturbances in multiple
      domains. The cerebellum is involved in both motor and non-motor functions, and
      the "cognitive dysmetria" and "dysmetria of thought" models propose that
      abnormalities of the cerebellum may contribute to schizophrenia signs and
      symptoms. The cerebellum and cerebral cortex are reciprocally connected via a
      modular, closed-loop network architecture, but few schizophrenia neuroimaging
      studies have taken into account the topographical and functional heterogeneity of
      the cerebellum. In this study, using a previously defined 17-network cerebral
      cortical parcellation system as the basis for our functional connectivity seeds,
      we systematically investigated connectivity abnormalities within the cerebellum
      of 44 schizophrenia patients and 28 healthy control participants. We found
      selective alterations in cerebro-cerebellar functional connectivity.
      Specifically, schizophrenia patients showed decreased cerebro-cerebellar
      functional connectivity in higher level association networks (ventral attention,
      salience, control, and default mode networks) relative to healthy control
      participants. Schizophrenia patients also showed increased cerebro-cerebellar
      connectivity in somatomotor and default mode networks, with the latter showing no
      overlap with the regions found to be hypoconnected within the same default mode
      network. Finally, we found evidence to suggest that somatomotor and default mode
      networks may be inappropriately linked in schizophrenia. The relationship of
      these dysconnectivities to schizophrenia symptoms, such as neurological soft
      signs and altered sense of agency, is discussed. We conclude that the cerebellum
      ought to be considered for analysis in all future studies of network
      abnormalities in SZ, and further suggest the cerebellum as a potential target for
      further elucidation, and possibly treatment, of the underlying mechanisms and
      network abnormalities producing symptoms of schizophrenia. 

PMID- 25852523
TI  - The Two-Wrongs model explains perception-action dissociations for illusions
      driven by distortions of the egocentric reference frame.
AB  - Several studies have demonstrated a dissociation of the effects of illusion on
      perception and action, with perception generally reported to be susceptible to
      illusions, while actions are seemingly immune. These findings have been
      interpreted to support Milner and Goodale's Two Visual Systems model, which
      proposes the existence of separate visual processing streams for perception and
      action. However, an alternative interpretation suggests that this type of
      behavioral dissociation will occur for any illusion that is caused by a
      distortion of the observer's egocentric reference frame, without requiring the
      existence of separate perception and action systems that are differently affected
      by the illusion. In this scenario, movements aimed at illusory targets will be
      accurate if they are guided within the same distorted reference frame used for
      target encoding, since the error of motor guidance will cancel with the error of
      encoding (hence, for actions, two wrongs do make a right). We further test this
      Two-Wrongs model by examining two illusions for which the hypothesis makes very
      different predictions: the rod-and-frame illusion (which affects perception but
      not actions) and the simultaneous-tilt illusion (which affects perception and
      actions equally). We demonstrate that the rod-and-frame illusion is caused by a
      distortion of the observer's egocentric reference frame suitable for the
      cancellation of errors predicted by the Two-Wrongs model. In contrast, the
      simultaneous-tilt illusion is caused by local interactions between stimulus
      elements within an undistorted reference frame, precluding the cancellation of
      errors associated with the Two-Wrongs model such that the illusion is reflected
      in both perception and actions. These results provide evidence for a class of
      illusions that lead to dissociations of perception and action through distortions
      of the observer's spatial reference frame, rather than through the actions of
      functionally separate visual processing streams. 

PMID- 25852525
TI  - A commentary on: Affective coding: the emotional dimension of agency.

PMID- 25852526
TI  - Cardiovascular and nervous system changes during meditation.
AB  - BACKGROUND: A number of benefits have been described for the long-term practice
      of meditation, yet little is known regarding the immediate neurological and
      cardiovascular responses to meditation. Wireless sensor technology allows, for
      the first time, multi-parameter and quantitative monitoring of an individual's
      responses during meditation. The present study examined inter-individual
      variations to meditation through continuous monitoring of EEG, blood pressure,
      heart rate and its variability (HRV) in novice and experienced meditators.
      METHODS: Participants were 20 experienced and 20 novice meditators involved in a
      week-long wellness retreat. Monitoring took place during meditation sessions on
      the first and last full days of the retreat. All participants wore a patch that
      continuously streamed ECG data, while half of them also wore a wireless EEG
      headset plus a non-invasive continuous blood pressure monitor. RESULTS:
      Meditation produced variable but characteristic EEG changes, significantly
      different from baseline, even among novice meditators on the first day. In
      addition, although participants were predominately normotensive, the mean
      arterial blood pressure fell a small (2-3 mmHg) but significant (p < 0.0001)
      amount during meditation. The effect of meditation on HRV was less clear and
      influenced by calculation technique and respiration. No clear relationship
      between EEG changes, HRV alterations, or mean blood pressure during meditation
      was found. CONCLUSION: This is the first study to investigate neurological and
      cardiovascular responses during meditation in both novice and experienced
      meditators using novel, wearable, wireless devices. Meditation produced varied
      inter-individual physiologic responses. These results support the need for
      further investigation of the short- and long-term cardiovascular effects of
      mental calm and individualized ways to achieve it.

PMID- 25852524
TI  - Over my fake body: body ownership illusions for studying the multisensory basis
      of own-body perception.
AB  - Which is my body and how do I distinguish it from the bodies of others, or from
      objects in the surrounding environment? The perception of our own body and more
      particularly our sense of body ownership is taken for granted. Nevertheless,
      experimental findings from body ownership illusions (BOIs), show that under
      specific multisensory conditions, we can experience artificial body parts or fake
      bodies as our own body parts or body, respectively. The aim of the present paper
      is to discuss how and why BOIs are induced. We review several experimental
      findings concerning the spatial, temporal, and semantic principles of crossmodal
      stimuli that have been applied to induce BOIs. On the basis of these principles,
      we discuss theoretical approaches concerning the underlying mechanism of BOIs. We
      propose a conceptualization based on Bayesian causal inference for addressing how
      our nervous system could infer whether an object belongs to our own body, using
      multisensory, sensorimotor, and semantic information, and we discuss how this can
      account for several experimental findings. Finally, we point to neural network
      models as an implementational framework within which the computational problem
      behind BOIs could be addressed in the future. 

PMID- 25852527
TI  - Synchrony between sensory and cognitive networks is associated with subclinical
      variation in autistic traits.
AB  - Individuals with autistic spectrum disorders exhibit distinct personality traits
      linked to attentional, social, and affective functions, and those traits are
      expressed with varying levels of severity in the neurotypical and subclinical
      population. Variation in autistic traits has been linked to reduced functional
      and structural connectivity (i.e., underconnectivity, or reduced synchrony) with
      neural networks modulated by attentional, social, and affective functions. Yet,
      it remains unclear whether reduced synchrony between these neural networks
      contributes to autistic traits. To investigate this issue, we used functional
      magnetic resonance imaging to record brain activation while neurotypical
      participants who varied in their subclinical scores on the Autism-Spectrum
      Quotient (AQ) viewed alternating blocks of social and nonsocial stimuli (i.e.,
      images of faces and of landscape scenes). We used independent component analysis
      (ICA) combined with a spatiotemporal regression to quantify synchrony between
      neural networks. Our results indicated that decreased synchrony between the
      executive control network (ECN) and a face-scene network (FSN) predicted higher
      scores on the AQ. This relationship was not explained by individual differences
      in head motion, preferences for faces, or personality variables related to social
      cognition. Our findings build on clinical reports by demonstrating that reduced
      synchrony between distinct neural networks contributes to a range of subclinical
      autistic traits. 

PMID- 25852528
TI  - Evidence for an inhibitory-control theory of the reasoning brain.
AB  - In this article, we first describe our general inhibitory-control theory and,
      then, we describe how we have tested its specific hypotheses on reasoning with
      brain imaging techniques in adults and children. The innovative part of this
      perspective lies in its attempt to come up with a brain-based synthesis of Jean
      Piaget's theory on logical algorithms and Daniel Kahneman's theory on intuitive
      heuristics. 

PMID- 25852530
TI  - Deep networks for motor control functions.
AB  - The motor system generates time-varying commands to move our limbs and body.
      Conventional descriptions of motor control and learning rely on dynamical
      representations of our body's state (forward and inverse models), and control
      policies that must be integrated forward to generate feedforward time-varying
      commands; thus these are representations across space, but not time. Here we
      examine a new approach that directly represents both time-varying commands and
      the resulting state trajectories with a function; a representation across space
      and time. Since the output of this function includes time, it necessarily
      requires more parameters than a typical dynamical model. To avoid the problems of
      local minima these extra parameters introduce, we exploit recent advances in
      machine learning to build our function using a stacked autoencoder, or deep
      network. With initial and target states as inputs, this deep network can be
      trained to output an accurate temporal profile of the optimal command and state
      trajectory for a point-to-point reach of a non-linear limb model, even when
      influenced by varying force fields. In a manner that mirrors motor babble, the
      network can also teach itself to learn through trial and error. Lastly, we
      demonstrate how this network can learn to optimize a cost objective. This
      functional approach to motor control is a sharp departure from the standard
      dynamical approach, and may offer new insights into the neural implementation of
      motor control. 

PMID- 25852531
TI  - Neural dynamics based on the recognition of neural fingerprints.
AB  - Experimental evidence has revealed the existence of characteristic spiking
      features in different neural signals, e.g., individual neural signatures
      identifying the emitter or functional signatures characterizing specific tasks.
      These neural fingerprints may play a critical role in neural information
      processing, since they allow receptors to discriminate or contextualize incoming
      stimuli. This could be a powerful strategy for neural systems that greatly
      enhances the encoding and processing capacity of these networks. Nevertheless,
      the study of information processing based on the identification of specific
      neural fingerprints has attracted little attention. In this work, we study (i)
      the emerging collective dynamics of a network of neurons that communicate with
      each other by exchange of neural fingerprints and (ii) the influence of the
      network topology on the self-organizing properties within the network. Complex
      collective dynamics emerge in the network in the presence of stimuli. Predefined
      inputs, i.e., specific neural fingerprints, are detected and encoded into
      coexisting patterns of activity that propagate throughout the network with
      different spatial organization. The patterns evoked by a stimulus can survive
      after the stimulation is over, which provides memory mechanisms to the network.
      The results presented in this paper suggest that neural information processing
      based on neural fingerprints can be a plausible, flexible, and powerful strategy.

PMID- 25852529
TI  - Dysfunctional Activation and Brain Network Profiles in Youth with Obsessive
      Compulsive Disorder: A Focus on the Dorsal Anterior Cingulate during Working
      Memory.
AB  - Brain network dysfunction is emerging as a central biomarker of interest in
      psychiatry, in large part, because psychiatric conditions are increasingly seen
      as disconnection syndromes. Understanding dysfunctional brain network profiles in
      task-active states provides important information on network engagement in an
      experimental context. This in turn may be predictive of many of the cognitive and
      behavioral deficits associated with complex behavioral phenotypes. Here we
      investigated brain network profiles in youth with obsessive-compulsive disorder
      (OCD), contrasting them with a group of age-comparable controls. Network
      interactions were assessed during simple working memory: in particular, we
      focused on the modulation by the dorsal anterior cingulate cortex (dACC) of
      cortical, striatal, and thalamic regions. The focus on the dACC was motivated by
      its hypothesized role in the pathophysiology of OCD. However, its task-active
      network signatures have not been investigated before. Network interactions were
      modeled using psychophysiological interaction, a simple directional model of seed
      to target brain interactions. Our results indicate that OCD is characterized by
      significantly increased dACC modulation of cortical, striatal, and thalamic
      targets during working memory, and that this aberrant increase in OCD patients is
      maintained regardless of working memory demand. The results constitute compelling
      evidence of dysfunctional brain network interactions in OCD and suggest that
      these interactions may be related to a combination of network inefficiencies and
      dACC hyper-activity that has been associated with the phenotype. 

PMID- 25852532
TI  - On the relationship among different motor processes: a computational modeling
      approach.

PMID- 25852533
TI  - RM-SORN: a reward-modulated self-organizing recurrent neural network.
AB  - Neural plasticity plays an important role in learning and memory. Reward
      modulation of plasticity offers an explanation for the ability of the brain to
      adapt its neural activity to achieve a rewarded goal. Here, we define a neural
      network model that learns through the interaction of Intrinsic Plasticity (IP)
      and reward-modulated Spike-Timing-Dependent Plasticity (STDP). IP enables the
      network to explore possible output sequences and STDP, modulated by reward,
      reinforces the creation of the rewarded output sequences. The model is tested on
      tasks for prediction, recall, non-linear computation, pattern recognition, and
      sequence generation. It achieves performance comparable to networks trained with
      supervised learning, while using simple, biologically motivated plasticity rules,
      and rewarding strategies. The results confirm the importance of investigating the
      interaction of several plasticity rules in the context of reward-modulated
      learning and whether reward-modulated self-organization can explain the amazing
      capabilities of the brain. 

PMID- 25852534
TI  - Detection of epileptiform activity in EEG signals based on time-frequency and non
      linear analysis.
AB  - We present a new technique for detection of epileptiform activity in EEG signals.
      After preprocessing of EEG signals we extract representative features in time,
      frequency and time-frequency domain as well as using non-linear analysis. The
      features are extracted in a few frequency sub-bands of clinical interest since
      these sub-bands showed much better discriminatory characteristics compared with
      the whole frequency band. Then we optimally reduce the dimension of feature space
      to two using scatter matrices. A decision about the presence of epileptiform
      activity in EEG signals is made by quadratic classifiers designed in the reduced
      two-dimensional feature space. The accuracy of the technique was tested on three
      sets of electroencephalographic (EEG) signals recorded at the University Hospital
      Bonn: surface EEG signals from healthy volunteers, intracranial EEG signals from
      the epilepsy patients during the seizure free interval from within the seizure
      focus and intracranial EEG signals of epileptic seizures also from within the
      seizure focus. An overall detection accuracy of 98.7% was achieved. 

PMID- 25852535
TI  - How the credit assignment problems in motor control could be solved after the
      cerebellum predicts increases in error.
AB  - We present a cerebellar architecture with two main characteristics. The first one
      is that complex spikes respond to increases in sensory errors. The second one is
      that cerebellar modules associate particular contexts where errors have increased
      in the past with corrective commands that stop the increase in error. We analyze
      our architecture formally and computationally for the case of reaching in a 3D
      environment. In the case of motor control, we show that there are synergies of
      this architecture with the Equilibrium-Point hypothesis, leading to novel ways to
      solve the motor error and distal learning problems. In particular, the presence
      of desired equilibrium lengths for muscles provides a way to know when the error
      is increasing, and which corrections to apply. In the context of Threshold
      Control Theory and Perceptual Control Theory we show how to extend our model so
      it implements anticipative corrections in cascade control systems that span from
      muscle contractions to cognitive operations. 

PMID- 25852537
TI  - The chronic challenge-new vistas on long-term multisite contacts to the central
      nervous system.

PMID- 25852536
TI  - A scalable neuroinformatics data flow for electrophysiological signals using
      MapReduce.
AB  - Data-driven neuroscience research is providing new insights in progression of
      neurological disorders and supporting the development of improved treatment
      approaches. However, the volume, velocity, and variety of neuroscience data
      generated from sophisticated recording instruments and acquisition methods have
      exacerbated the limited scalability of existing neuroinformatics tools. This
      makes it difficult for neuroscience researchers to effectively leverage the
      growing multi-modal neuroscience data to advance research in serious neurological
      disorders, such as epilepsy. We describe the development of the Cloudwave data
      flow that uses new data partitioning techniques to store and analyze
      electrophysiological signal in distributed computing infrastructure. The
      Cloudwave data flow uses MapReduce parallel programming algorithm to implement an
      integrated signal data processing pipeline that scales with large volume of data
      generated at high velocity. Using an epilepsy domain ontology together with an
      epilepsy focused extensible data representation format called Cloudwave Signal
      Format (CSF), the data flow addresses the challenge of data heterogeneity and is
      interoperable with existing neuroinformatics data representation formats, such as
      HDF5. The scalability of the Cloudwave data flow is evaluated using a 30-node
      cluster installed with the open source Hadoop software stack. The results
      demonstrate that the Cloudwave data flow can process increasing volume of signal
      data by leveraging Hadoop Data Nodes to reduce the total data processing time.
      The Cloudwave data flow is a template for developing highly scalable neuroscience
      data processing pipelines using MapReduce algorithms to support a variety of user
      applications. 

PMID- 25852538
TI  - A case of dermatomyositis with esophageal fistula in whom blind mucosal biopsy
      detected occult oropharyngeal carcinoma.
AB  - We present a case of anti-transcription intermediary factor 1 (anti-TIF-1)
      antibody-positive dermatomyositis with concomitant esophageal fistula and
      extensive truncal erythema. The characteristic cutaneous features and presence of
      anti-TIF-1 antibodies were predictive for internal malignancy. However, repeated
      examinations for internal malignancy showed none, and blind mucosal biopsy was
      needed to diagnose oropharyngeal carcinoma. We should note the possibility of
      occult nasopharyngeal carcinoma and consider performing blind mucosal biopsy in
      dermatomyositis with esophageal fistula, especially with extensive truncal
      erythema. 

PMID- 25852539
TI  - Modified muscle transposition procedure for a case of inferior rectus muscle
      aplasia.
AB  - PURPOSE: We report a case of inferior rectus muscle aplasia in a 65-year-old
      woman. METHODS: Images were obtained using ocular motility photography and
      magnetic resonance imaging (MRI), and operative findings were analyzed. RESULTS:
      A 65-year-old woman presented with marked right hypertropia. The right eye also
      had microcornea, iris coloboma, and completely restricted downward movement. MRI
      showed absence of the inferior rectus muscle in both eyes. During surgery, it was
      confirmed that the right inferior rectus muscle was absent. The patient underwent
      a muscle transposition procedure without tenotomy or muscle splitting. A superior
      rectus muscle tenotomy was also performed. Postoperatively, the right eye showed
      hypotropia and improved downward movement. CONCLUSION: Muscle transposition
      without tenotomy or tendon splitting is a surgical option for the unusual
      abnormality presented in this paper.

PMID- 25852540
TI  - Compartmental distribution of GABAB receptor-mediated currents along the
      somatodendritic axis of hippocampal principal cells.
AB  - Activity of cortical principal cells is controlled by the GABAergic system
      providing inhibition in a compartmentalized manner along their somatodendritic
      axis. While GABAAR-mediated inhibitory synaptic transmission has been extensively
      characterized in hippocampal principal cells, little is known about the
      distribution of postsynaptic effects of GABABRs. In the present study, we have
      investigated the functional localization of GABABRs and their effector inwardly
      rectifying potassium (Kir3) channels by combining electrophysiological recordings
      in acute rat hippocampal slices, high-resolution immunoelectron microscopic
      analysis and single cell simulations. Pharmacologically isolated slow inhibitory
      postsynaptic currents were elicited in the three major hippocampal principal cell
      types by endogenous GABA released by electrical stimulation, photolysis of caged
      GABA, as well as the canonical agonist baclofen, with the highest amplitudes
      observed in the CA3. Spatially restricted currents were assessed along the axis
      of principal cells by uncaging GABA in the different hippocampal layers. GABABR
      mediated currents were present along the entire somatodendritic axis of principal
      cells, but non-uniformly distributed: largest currents and the highest
      conductance densities determined in the simulations were consistently found on
      the distal apical dendrites. Finally, immunocytochemical localization of GABABRs
      and Kir3 channels showed that distributions overlap but their densities diverge,
      particularly on the basal dendrites of pyramidal cells. GABABRs current
      amplitudes and the conductance densities correlated better with Kir3 density,
      suggesting a bottlenecking effect defined by the effector channel. These data
      demonstrate a compartmentalized distribution of the GABABR-Kir3 signaling cascade
      and suggest differential control of synaptic transmission, dendritic integration
      and synaptic plasticity at afferent pathways onto hippocampal principal cells. 

PMID- 25852541
TI  - Impaired emotional autobiographical memory associated with right amygdalar
      hippocampal atrophy in Alzheimer's disease patients.
AB  - We studied the influence of emotions on autobiographical memory (AbM) in patients
      with Alzheimer's disease (AD), characteristically triggering atrophy in the
      hippocampus and the amygdala, two crucial structures sustaining memory and
      emotional processing. Our first aim was to analyze the influence of emotion on
      AbM in AD patients, on both the proportion and the specificity of emotional
      memories. Additionally, we sought to determine the relationship of emotional AbM
      to amygdalar-hippocampal volumes. Eighteen prodromal to mild AD patients and 18
      age-matched healthy controls were included. We obtained 30 autobiographical
      memories per participant using the modified Crovitz test (MCT). Analyses were
      performed on global scores, rates and specificity scores of the emotional vs.
      neutral categories of memories. Amygdalar-hippocampal volumes were extracted from
      3D T1-weighted MRI scans and tested for correlations with behavioral data.
      Overall, AD patients displayed a deficit in emotional AbMs as they elicited less
      emotional memories than the controls, however, the specificity of those memories
      was preserved. The deficit likely implied retrieval or storage as it was extended
      in time and without reminiscence bump effect. Global scores and rates of
      emotional memories, but not the specificity scores, were correlated to right
      amygdalar and hippocampal volumes, indicating that atrophy in these structures
      has a central role in the deficit observed. Conversely, emotional memories were
      more specific than neutral memories in both groups, reflecting an enhancement
      effect of emotion that could be supported by other brain regions that are spared
      during the early stages of the disease. 

PMID- 25852542
TI  - 'Kitchen and cooking,' a serious game for mild cognitive impairment and
      Alzheimer's disease: a pilot study.
AB  - Recently there has been a growing interest in employing serious games (SGs) for
      the assessment and rehabilitation of elderly people with mild cognitive
      impairment (MCI), Alzheimer's disease (AD), and related disorders. In the present
      study we examined the acceptability of 'Kitchen and cooking' - a SG developed in
      the context of the EU project VERVE (http://www.verveconsortium.eu/) - in these
      populations. In this game a cooking plot is employed to assess and stimulate
      executive functions (such as planning abilities) and praxis. The game is
      installed on a tablet, to be flexibly employed at home and in nursing homes.
      Twenty one elderly participants (9 MCI and 12 AD, including 14 outpatients and 7
      patients living in nursing homes, as well as 11 apathetic and 10 non-apathetic)
      took part in a 1-month trail, including a clinical and neuropsychological
      assessment, and 4-week training where the participants were free to play as long
      as they wanted on a personal tablet. During the training, participants met once a
      week with a clinician in order to fill in self-report questionnaires assessing
      their overall game experience (including acceptability, motivation, and perceived
      emotions). The results of the self reports and of the data concerning game
      performance (e.g., time spent playing, number of errors, etc) confirm the overall
      acceptability of Kitchen and cooking for both patients with MCI and patients with
      AD and related disorders, and the utility to employ it for training purposes.
      Interestingly, the results confirm that the game is adapted also to apathetic
      patients. 

PMID- 25852543
TI  - The influence of aging on the number of neurons and levels of non-phosporylated
      neurofilament proteins in the central auditory system of rats.
AB  - In the present study, an unbiased stereological method was used to determine the
      number of all neurons in Nissl stained sections of the inferior colliculus (IC),
      medial geniculate body (MGB), and auditory cortex (AC) in rats (strains Long
      Evans and Fischer 344) and their changes with aging. In addition, using the
      optical fractionator and western blot technique, we also evaluated the number of
      SMI-32-immunoreactive (-ir) neurons and levels of non-phosphorylated
      neurofilament proteins in the IC, MGB, AC, and visual cortex of young and old
      rats of the two strains. The SMI-32 positive neuronal population comprises about
      10% of all neurons in the rat IC, MGB, and AC and represents a prevalent
      population of large neurons with highly myelinated and projecting processes. In
      both Long Evans and Fischer 344 rats, the total number of neurons in the IC was
      roughly similar to that in the AC. With aging, we found a rather mild and
      statistically non-significant decline in the total number of neurons in all three
      analyzed auditory regions in both rat strains. In contrast to this, the absolute
      number of SMI-32-ir neurons in both Long Evans and Fischer 344 rats significantly
      decreased with aging in all the examined structures. The western blot technique
      also revealed a significant age-related decline in the levels of non
      phosphorylated neurofilaments in the auditory brain structures, 30-35%. Our
      results demonstrate that presbycusis in rats is not likely to be primarily
      associated with changes in the total number of neurons. On the other hand, the
      pronounced age-related decline in the number of neurons containing non
      phosphorylated neurofilaments as well as their protein levels in the central
      auditory system may contribute to age-related deterioration of hearing function. 

PMID- 25852544
TI  - Differences in temporal order memory among young, middle-aged, and older adults
      may depend on the level of interference.
AB  - Age-related changes in temporal order memory have been well documented in older
      adults; however, little is known about this ability during middle age. We tested
      healthy young, middle-aged, and older adults on a previously published
      visuospatial temporal order memory test involving high and low interference
      conditions. When interference was low, young and middle-aged adults did not
      differ, but both groups significantly outperformed older adults. However, when
      interference was high, significant differences were found among all three age
      groups. The data provide evidence that temporal order memory may begin to decline
      in middle age, particularly when temporal interference is high. 

PMID- 25852545
TI  - Regional and sub-regional differences in hippocampal GABAergic neuronal
      vulnerability in the TgCRND8 mouse model of Alzheimer's disease.
AB  - Hippocampal network activity is predominantly coordinated by gamma-amino-butyric
      acid (GABA)ergic neurons. We have previously hypothesized that the altered
      excitability of hippocampal neurons in Alzheimer's disease (AD), which manifests
      as increased in vivo susceptibility to seizures in the TgCRND8 mouse model of AD,
      may be related to disruption of hippocampal GABAergic neurons. In agreement, our
      previous study in TgCRND8 mice has shown that hippocampal GABAergic neurons are
      more vulnerable to AD-related neuropathology than other types of neurons. To
      further explore the mechanisms behind the observed decrease of GABAergic neurons
      in 6 month-old TgCRND8 mice, we assessed the relative proportion of somatostatin
      (SOM), neuropeptide Y (NPY) and paravalbumin (PV) sub-types of GABAergic neurons
      at the regional and sub-regional level of the hippocampus. We found that NPY
      expressing GABAergic neurons were the most affected, as they were decreased in
      CA1-CA2 (pyramidal-, stratum oriens, stratum radiatum and molecular layers), CA3
      (specifically in the stratum oriens) and dentate gyrus (specifically in the
      polymorphic layer) in TgCRND8 mice as compared to non-transgenic controls. SOM
      expressing GABAergic neurons were decreased in CA1-CA2 (specifically in the
      stratum oriens) and in the stratum radiatum of CA3, whereas PV neurons were
      significantly altered in stratum oriens sub-region of CA3. Taken together, these
      data provide new evidence for the relevance of hippocampal GABAergic neuronal
      network disruption as a mechanism underlying AD sequelae such as aberrant
      neuronal excitability, and further point to complex hippocampal regional and sub
      regional variation in susceptibility to AD-related neuronal loss. 

PMID- 25852546
TI  - Transforming growth factor beta1 inhibition protects from noise-induced hearing
      loss.
AB  - Excessive exposure to noise damages the principal cochlear structures leading to
      hearing impairment. Inflammatory and immune responses are central mechanisms in
      cochlear defensive response to noise but, if unregulated, they contribute to
      inner ear damage and hearing loss. Transforming growth factor beta (TGF-beta) is
      a key regulator of both responses and high levels of this factor have been
      associated with cochlear injury in hearing loss animal models. To evaluate the
      potential of targeting TGF-beta as a therapeutic strategy for preventing or
      ameliorating noise-induced hearing loss (NIHL), we studied the auditory function,
      cochlear morphology, gene expression and oxidative stress markers in mice exposed
      to noise and treated with TGF-beta1 peptidic inhibitors P17 and P144, just before
      or immediately after noise insult. Our results indicate that systemic
      administration of both peptides significantly improved both the evolution of
      hearing thresholds and the degenerative changes induced by noise-exposure in
      lateral wall structures. Moreover, treatments ameliorated the inflammatory state
      and redox balance. These therapeutic effects were dose-dependent and more
      effective if the TGF-beta1 inhibitors were administered prior to inducing the
      injury. In conclusion, inhibition of TGF-beta1 actions with antagonistic peptides
      represents a new, promising therapeutic strategy for the prevention and repair of
      noise-induced cochlear damage. 

PMID- 25852547
TI  - Inner ear hair cells deteriorate in mice engineered to have no or diminished
      innervation.
AB  - The innervation of the inner ear critically depends on the two neurotrophins Ntf3
      and Bdnf. In contrast to this molecularly well-established dependency, evidence
      regarding the need of innervation for long-term maintenance of inner ear hair
      cells is inconclusive, due to experimental variability. Mutant mice that lack
      both neurotrophins could shed light on the long-term consequences of innervation
      loss on hair cells without introducing experimental variability, but do not
      survive after birth. Mutant mice with conditional deletion of both neurotrophins
      lose almost all innervation by postnatal day 10 and show an initially normal
      development of hair cells by this stage. No innervation remains after 3 weeks and
      complete loss of all innervation results in near complete loss of outer and many
      inner hair cells of the organ of Corti within 4 months. Mutants that retain one
      allele of either neurotrophin have only partial loss of innervation of the organ
      of Corti and show a longer viability of cochlear hair cells with more profound
      loss of inner hair cells. By 10 months, hair cells disappear with a base to apex
      progression, proportional to the residual density of innervation and similar to
      carboplatin ototoxicity. Similar to reports of hair cell loss after
      aminoglycoside treatment, blobbing of stereocilia of apparently dying hair cells
      protrude into the cochlear duct. Denervation of vestibular sensory epithelia for
      several months also resulted in variable results, ranging from unusual hair cells
      resembling the aberrations found in the organ of Corti, to near normal hair cells
      in the canal cristae. Fusion and/or resorption of stereocilia and loss of hair
      cells follows a pattern reminiscent of Myo6 and Cdc42 null mice. Our data support
      a role of innervation for long-term maintenance but with a remarkable local
      variation that needs to be taken into account when attempting regeneration of the
      organ of Corti. 

PMID- 25852548
TI  - Longitudinal assessment of neuropsychological and temporal/spatial gait
      characteristics of elderly fallers: taking it all in stride.
AB  - Gait abnormalities are linked to cognitive decline and an increased fall risk
      within older adults. The present study addressed gaps from cross-sectional
      studies in the literature by longitudinally examining the interplay between
      temporal and spatial aspects of gait, cognitive function, age, and lower
      extremity strength in elderly "fallers" and "non-fallers". Gait characteristics,
      neuropsychological and physical test performance were examined at two time points
      spaced a year apart in cognitively intact individuals aged 60 and older (N =
      416). Mixed-model repeated-measure ANCOVAs examined temporal (step time) and
      spatial (stride length) gait characteristics during a simple and cognitive-load
      walking task in fallers as compared to non-fallers. Fallers consistently
      demonstrated significant alterations in spatial, but not temporal, aspects of
      gait as compared to non-fallers during both walking tasks. Step time became
      slower as stride length shortened amongst all participants during the dual task.
      Shorter strides and slower step times during the dual task were both predicted by
      worse executive attention/processing speed performance. In summary, divided
      attention significantly impacts spatial aspects of gait in "fallers", suggesting
      stride length changes may precede declines in other neuropsychological and gait
      characteristics, thereby selectively increasing fall risk. Our results indicate
      that multimodal intervention approaches that integrate physical and cognitive
      remediation strategies may increase the effectiveness of fall risk interventions.

PMID- 25852549
TI  - Differences in cognitive aging: typology based on a community structure detection
      approach.
AB  - The current study investigated the extent and patterns of cognitive variability
      in younger and older adults. An important novelty of this study is the use of
      graph-based community structure detection analysis to map performance in a mixed
      population of 79 young and 76 older adults, without separating the age groups a
      priori. We identified six subgroups, with distinct patterns of neuropsychological
      performance. The stability of the identified subgroups was confirmed by employing
      a cross-validation support vector machine based analysis. The majority of these
      subgroups comprised either young or older adults, confirming the expected role of
      aging in cognitive performance. In addition, we identified a subgroup of young
      and older adults who performed at a similar cognitive level of overall good
      cognitive performance with slightly decreased processing speed. This result
      showed that older age is not necessarily associated with general lower cognitive
      performance and that being young is not necessarily associated with superior
      cognitive performance. Moreover, cognitively better performing elderly had a
      significantly higher level of education attainment and higher crystallized
      intelligence than the other elderly, which suggests that older adults with higher
      cognitive reserve may be able to cope better with age-related neurobiological
      change. 

PMID- 25852550
TI  - Lower limb progressive resistance training improves leg strength but not gait
      speed or balance in Parkinson's disease: a systematic review and meta-analysis.
AB  - The use of progressive resistance training (PRT) to improve gait and balance in
      people with Parkinson's disease (PD) is an emerging area of interest. However,
      the main effects of PRT on lower limb functions such as gait, balance, and leg
      strength in people with PD remain unclear. Therefore, the aim of the meta
      analysis is to evaluate the evidence surrounding the use of PRT to improve gait
      and balance in people with PD. Five electronic databases, from inception to
      December 2014, were searched to identify the relevant studies. Data extraction
      was performed by two independent reviewers and methodological quality was
      assessed using the PEDro scale. Standardized mean differences (SMD) and 95%
      confidence intervals (CIs) of fixed and random effects models were used to
      calculate the effect sizes between experimental and control groups and I (2)
      statistics were used to determine levels of heterogeneity. In total, seven
      studies were identified consisting of 172 participants (experimental n = 84;
      control n = 88). The pooled results showed a moderate but significant effect of
      PRT on leg strength (SMD 1.42, 95% CI 0.464-2.376); however, no significant
      effects were observed for gait speed (SMD 0.418, 95% CI -0.219 to 1.055). No
      significant effects were observed for balance measures included in this review.
      In conclusion, our results showed no discernable effect of PRT on gait and
      balance measures, although this is likely due to the lack of studies available.
      It may be suggested that PRT be performed in conjunction with balance or task
      specific functional training to elicit greater lower limb functional benefits in
      people with PD. 

PMID- 25852552
TI  - Peptide ligand recognition by G protein-coupled receptors.
AB  - The past few years have seen spectacular progress in the structure determination
      of G protein-coupled receptors (GPCRs). We now have structural representatives
      from classes A, B, C, and F. Within the rhodopsin-like class A, most structures
      belong to the alpha group, whereas fewer GPCR structures are available from the
      beta, gamma, and delta groups, which include peptide GPCRs such as the receptors
      for neurotensin (beta group), opioids, chemokines (gamma group), and protease
      activated receptors (delta group). Structural information on peptide GPCRs is
      restricted to complexes with non-peptidic drug-like antagonists with the
      exception of the chemokine receptor CXCR4 that has been crystallized in the
      presence of a cyclic peptide antagonist. Notably, the neurotensin receptor 1 is
      to date the only peptide GPCR whose structure has been solved in the presence of
      a peptide agonist. Although limited in number, the current peptide GPCR
      structures reveal great diversity in shape and electrostatic properties of the
      ligand binding pockets, features that play key roles in the discrimination of
      ligands. Here, we review these aspects of peptide GPCRs in view of possible
      models for peptide agonist binding. 

PMID- 25852553
TI  - IL-1 interacts with ethanol effects on GABAergic transmission in the mouse
      central amygdala.
AB  - Neuroinflammation is hypothesized to enhance alcohol consumption and contribute
      to the development of alcoholism. GABAergic transmission in the central amygdala
      (CeA) plays an important role in the transition to alcohol dependence. Therefore,
      we studied the effects of interleukin-1beta (IL-1beta), a proinflammatory
      cytokine mediating ethanol-induced neuroinflammation, and its interaction with
      ethanol on CeA GABAegic transmission in B6129SF2/J mice. We also assessed ethanol
      intake in B6129SF2/J mice. Intake with unlimited (24 h) ethanol access was 9.2
      12.7 g/kg (3-15% ethanol), while limited (2 h) access produced an intake of 4.1
      +/- 0.5 g/kg (15% ethanol). In our electrophysiology experiments, we found that
      recombinant IL-1beta (50 and 100 ng/ml) significantly decreased the amplitude of
      evoked inhibitory postsynaptic potentials (eIPSPs), with no significant effects
      on paired-pulse facilitation (PPF). IL-1beta (50 ng/ml) had dual effects on
      spontaneous miniature inhibitory postsynaptic currents (mIPSCs): increasing mIPSC
      frequencies in most CeA neurons, but decreasing both mIPSC frequencies and
      amplitudes in a few cells. The IL-1beta receptor antagonist (IL-1ra; 100 ng/ml)
      also had dual effects on mIPSCs and prevented the actions of IL-1beta on mIPSC
      frequencies. These results suggest that IL-1beta can alter CeA GABAergic
      transmission at pre- and postsynaptic sites. Ethanol (44 mM) significantly
      increased eIPSP amplitudes, decreased PPFs, and increased mIPSC frequencies. IL
      1beta did not alter ethanol's enhancement of the eIPSP amplitude, but, in IL
      1beta-responsive neurons, the ethanol effects on mIPSC frequencies were lost.
      Overall, our data suggest that the IL-1 system is involved in basal GABAergic
      transmission and that IL-1beta interacts with the ethanol-induced facilitation of
      CeA GABAergic transmission. 

PMID- 25852551
TI  - Central serotonin-2A (5-HT2A) receptor dysfunction in depression and epilepsy:
      the missing link?
AB  - 5-Hydroxytryptamine 2A receptors (5-HT2A-Rs) are G-protein coupled receptors. In
      agreement with their location in the brain, they have been implicated not only in
      various central physiological functions including memory, sleep, nociception,
      eating and reward behaviors, but also in many neuropsychiatric disorders.
      Interestingly, a bidirectional link between depression and epilepsy is suspected
      since patients with depression and especially suicide attempters have an
      increased seizure risk, while a significant percentage of epileptic patients
      suffer from depression. Such epidemiological data led us to hypothesize that both
      pathologies may share common anatomical and neurobiological alteration of the 5
      HT2A signaling. After a brief presentation of the pharmacological properties of
      the 5-HT2A-Rs, this review illustrates how these receptors may directly or
      indirectly control neuronal excitability in most networks involved in depression
      and epilepsy through interactions with the monoaminergic, GABAergic and
      glutamatergic neurotransmissions. It also synthetizes the preclinical and
      clinical evidence demonstrating the role of these receptors in antidepressant and
      antiepileptic responses. 

PMID- 25852555
TI  - NK cell tolerance as the final endorsement of prenatal tolerance after in utero
      hematopoietic cellular transplantation.
AB  - The primary benefits of in utero hematopoietic cellular transplantation (IUHCT)
      arise from transplanting curative cells prior to the immunologic maturation of
      the fetus. However, this approach has been routinely successful only in the
      treatment of congenital immunodeficiency diseases that include an inherent NK
      cell deficiency despite the existence of normal maternal immunity in either
      setting. These observations raise the possibility that fetal NK cells function as
      an early barrier to allogeneic IUHCT. Herein, we summarize the findings of
      previous studies of prenatal NK cell allospecific tolerance in mice and in
      humans. Cumulatively, this new information reveals the complexity of the fetal
      immune response in the setting of rejection or tolerance and illustrates the role
      for fetal NK cells in the final endorsement of allospecific prenatal tolerance. 

PMID- 25852554
TI  - Rodent models to study the metabolic effects of shiftwork in humans.
AB  - Our current 24-h society requires an increasing number of employees to work
      nightshifts with millions of people worldwide working during the evening or
      night. Clear associations have been found between shiftwork and the risk to
      develop metabolic health problems, such as obesity. An increasing number of
      studies suggest that the underlying mechanism includes disruption of the
      rhythmically organized body physiology. Normally, daily 24-h rhythms in
      physiological processes are controlled by the central clock in the brain in close
      collaboration with peripheral clocks present throughout the body. Working
      schedules of shiftworkers greatly interfere with these normal daily rhythms by
      exposing the individual to contrasting inputs, i.e., at the one hand (dim)light
      exposure at night, nightly activity and eating and at the other hand daytime
      sleep and reduced light exposure. Several different animal models are being used
      to mimic shiftwork and study the mechanism responsible for the observed
      correlation between shiftwork and metabolic diseases. In this review we aim to
      provide an overview of the available animal studies with a focus on the four most
      relevant models that are being used to mimic human shiftwork: altered timing of
      (1) food intake, (2) activity, (3) sleep, or (4) light exposure. For all studies
      we scored whether and how relevant metabolic parameters, such as bodyweight,
      adiposity and plasma glucose were affected by the manipulation. In the
      discussion, we focus on differences between shiftwork models and animal species
      (i.e., rat and mouse). In addition, we comment on the complexity of shiftwork as
      an exposure and the subsequent difficulties when using animal models to
      investigate this condition. In view of the added value of animal models over
      human cohorts to study the effects and mechanisms of shiftwork, we conclude with
      recommendations to improve future research protocols to study the causality
      between shiftwork and metabolic health problems using animal models. 

PMID- 25852556
TI  - Genetic determinants for methotrexate response in juvenile idiopathic arthritis.
AB  - Juvenile idiopathic arthritis (JIAs) is the most common chronic rheumatic disease
      of childhood and is an important cause of disability. The folic acid analog
      methotrexate is the first choice disease-modifying anti-rheumatic drug in this
      disease, however, 35-45% of patients fail to respond. Molecular elements, such as
      variants in genes of pharmacological relevance, influencing response to
      methotrexate in JIA, would be important to individualize treatment strategies.
      Several studies have evaluated the effects of candidate genetic variants in the
      complex pathway of genes involved in methotrexate pharmacodynamics and
      pharmacokinetics, however, results are still contrasting and no definitive
      genetic marker of methotrexate response useful for the clinician to tailor
      therapy of children with JIA has been identified. Recently, genome-wide
      approaches have been applied, identifying new potential biological processes
      involved in methotrexate response in JIA such as TGF-beta signaling and calcium
      channels. If these genomic results are properly validated and integrated with
      innovative analyses comprising deep sequencing, epigenetics, and
      pharmacokinetics, they will greatly contribute to personalize therapy with
      methotrexate in children with JIA. 

PMID- 25852557
TI  - M2 polarization enhances silica nanoparticle uptake by macrophages.
AB  - While silica nanoparticles have enabled numerous industrial and medical
      applications, their toxicological safety requires further evaluation. Macrophages
      are the major cell population responsible for nanoparticle clearance in vivo. The
      prevailing macrophage phenotype largely depends on the local immune status of the
      host. Whereas M1-polarized macrophages are considered as pro-inflammatory
      macrophages involved in host defense, M2 macrophages exhibit anti-inflammatory
      and wound-healing properties, but also promote tumor growth. We employed
      different models of M1 and M2 polarization: granulocyte-macrophage colony
      stimulating factor/lipopolysaccharide (LPS)/interferon (IFN)-gamma was used to
      generate primary human M1 cells and macrophage colony-stimulating factor (M
      CSF)/interleukin (IL)-10 to differentiate M2 monocyte-derived macrophages (MDM).
      PMA-differentiated THP-1 cells were polarized towards an M1 type by LPS/IFN-gamma
      and towards M2 by IL-10. Uptake of fluorescent silica nanoparticles (O26 and 41
      nm) and microparticles (O1.75 MUm) was quantified. At the concentration used (50
      MUg/ml), silica nanoparticles did not influence cell viability as assessed by MTT
      assay. Nanoparticle uptake was enhanced in M2-polarized primary human MDM
      compared with M1 cells, as shown by flow cytometric and microscopic approaches.
      In contrast, the uptake of microparticles did not differ between M1 and M2
      phenotypes. M2 polarization was also associated with increased nanoparticle
      uptake in the macrophage-like THP-1 cell line. In accordance, in vivo polarized
      M2-like primary human tumor-associated macrophages obtained from lung tumors took
      up more nanoparticles than M1-like alveolar macrophages isolated from the
      surrounding lung tissue. In summary, our data indicate that the M2 polarization
      of macrophages promotes nanoparticle internalization. Therefore, the phenotypical
      differences between macrophage subsets should be taken into consideration in
      future investigations on nanosafety, but might also open up therapeutic
      perspectives allowing to specifically target M2 polarized macrophages. 

PMID- 25852558
TI  - Effect of ultra violet irradiation on the interplay between Th1 and Th2
      lymphocytes.
AB  - Although ultraviolet (UV) radiation is used to treat several types of diseases,
      including rickets, psoriasis, eczema, and jaundice, the prolonged exposure to its
      radiation may result in acute and chronic health effects particularly on the
      skin, eyes, and the immune system. AIM: This study was carried out to show the
      effect of UV on both of the lymphoproliferative response and their capacity to
      produce IL-12 and IL-10 in mice. METHODS: Mice were exposed to whole body UVB and
      tested for the effect of recovery times on lymphocyte proliferation and cytokine
      production. In addition, direct irradiation of spleens and lymphocyte suspension
      was carried out. Basal and mitogens-stimulated lymphocyte proliferation was
      assessed by MTT assay while IL-10 and IL-12 were measured using ELISA. RESULTS:
      There was a significant suppression in lymphocyte proliferation in comparison
      with control. IL-12 level was significantly reduced while the level of IL-10 was
      increased. Con A and PWM mitogens had no significant changes in IL-10 while Con A
      caused a highly significant increase in IL-12 at day 6 of recovery in UVB body
      irradiation. CONCLUSION: Exposure to UVB radiation could cause a state of immune
      suppression and shifts Th1/Th2 cell response. This effect is closely associated
      with the reduction of Th1 cytokines' expression and increase in Th2 cytokines'
      levels.

PMID- 25852560
TI  - A new classifier-based strategy for in-silico ion-channel cardiac drug safety
      assessment.
AB  - There is currently a strong interest in using high-throughput in-vitro ion
      channel screening data to make predictions regarding the cardiac toxicity
      potential of a new compound in both animal and human studies. A recent FDA think
      tank encourages the use of biophysical mathematical models of cardiac myocytes
      for this prediction task. However, it remains unclear whether this approach is
      the most appropriate. Here we examine five literature data-sets that have been
      used to support the use of four different biophysical models and one statistical
      model for predicting cardiac toxicity in numerous species using various
      endpoints. We propose a simple model that represents the balance between
      repolarisation and depolarisation forces and compare the predictive power of the
      model against the original results (leave-one-out cross-validation). Our model
      showed equivalent performance when compared to the four biophysical models and
      one statistical model. We therefore conclude that this approach should be further
      investigated in the context of early cardiac safety screening when in-vitro
      potency data is generated. 

PMID- 25852561
TI  - 7alpha, 25-dihydroxycholesterol-mediated activation of EBI2 in immune regulation
      and diseases.
AB  - EBI2, aka GPR183, is a G-couple receptor originally identified in 1993 as one of
      main genes induced in Burkitt's lymphoma cell line BL41 by Epstein-Barr virus
      (EBV) infection. After it was reported in 2009 that the receptor played a key
      role in regulating B cell migration and responses, we initiated an effort in
      looking for its endogenous ligand. In 2011 we and another group reported the
      identification of 7alpha, 25-dihydroxyxcholesterol (7alpha, 25-OHC), an
      oxysterol, as the likely physiological ligand of EBI2. A few subsequently
      published studies further elucidated how 7alpha, 25-OHC bound to EBI2, and how a
      gradient of 7alpha, 25-OHC could be generated in vivo and regulated migration,
      activation, and functions of B cells, T cells, dendritic cells (DCs),
      monocytes/macrophages, and astrocytes. The identification of 7alpha, 25-OHC as a
      G protein-coupled receptor ligand revealed a previously unknown signaling system
      of oxysterols, a class of molecules which exert profound biological functions.
      Dysregulation of the synthesis or functions of these molecules is believed to
      contribute to inflammation and autoimmune diseases, cardiovascular diseases,
      neurodegenerative diseases, cancer as well as metabolic diseases such as
      diabetes, obesity, and dyslipidemia. Therefore EBI2 may represent a promising
      target for therapeutic interventions for human diseases. 

PMID- 25852559
TI  - Progress in antiandrogen design targeting hormone binding pocket to circumvent
      mutation based resistance.
AB  - Androgen receptor (AR) plays a critical role in the development and progression
      of prostate cancer (PCa). Current clinically used antiandrogens such as
      flutamide, bicalutamide, and newly approved enzalutamide mainly target the
      hormone binding pocket (HBP) of AR. However, over time, drug resistance
      invariably develops and switches these antiandrogens from antagonist to agonist
      of the AR. Accumulated evidence indicates that AR mutation is an important cause
      for the drug resistance. This review will give an overview of the mutation based
      resistance of the current clinically used antiandrogens and the rational drug
      design to overcome the resistance, provides a promising strategy for the
      development of the new generation of antiandrogens targeting HBP. 

PMID- 25852562
TI  - Mapping residual organics and carbonate at grain boundaries and the amorphous
      interphase in mouse incisor enamel.
AB  - Dental enamel has evolved to resist the most grueling conditions of mechanical
      stress, fatigue, and wear. Adding insult to injury, it is exposed to the
      frequently corrosive environment of the oral cavity. While its hierarchical
      structure is unrivaled in its mechanical resilience, heterogeneity in the
      distribution of magnesium ions and the presence of Mg-substituted amorphous
      calcium phosphate (Mg-ACP) as an intergranular phase have recently been shown to
      increase the susceptibility of mouse enamel to acid attack. Herein we investigate
      the distribution of two important constituents of enamel, residual organic matter
      and inorganic carbonate. We find that organics, carbonate, and possibly water
      show distinct distribution patterns in the mouse enamel crystallites, at simple
      grain boundaries, and in the amorphous interphase at multiple grain boundaries.
      This has implications for the resistance to acid corrosion, mechanical
      properties, and the mechanism by which enamel crystals grow during amelogenesis. 

PMID- 25852563
TI  - The pathophysiology of intestinal lipoprotein production.
AB  - Intestinal lipoprotein production is a multistep process, essential for the
      absorption of dietary fats and fat-soluble vitamins. Chylomicron assembly begins
      in the endoplasmic reticulum with the formation of primordial, phospholipids-rich
      particles that are then transported to the Golgi for secretion. Several classes
      of transporters play a role in the selective uptake and/or export of lipids
      through the villus enterocytes. Once secreted in the lymph stream, triglyceride
      rich lipoproteins (TRLs) are metabolized by Lipoprotein lipase (LPL), which
      catalyzes the hydrolysis of triacylglycerols of very low density lipoproteins
      (VLDLs) and chylomicrons, thereby delivering free fatty acids to various tissues.
      Genetic mutations in the genes codifying for these proteins are responsible of
      different inherited disorders affecting chylomicron metabolism. This review
      focuses on the molecular pathways that modulate the uptake and the transport of
      lipoproteins of intestinal origin and it will highlight recent findings on TRLs
      assembly. 

PMID- 25852564
TI  - Physiology of pericardial fluid production and drainage.
AB  - The pericardium is one of the serosal cavities of the mammals. It consists of two
      anatomical structures closely connected, an external sac of fibrous connective
      tissue, that is called fibrous pericardium and an internal that is called serous
      pericardium coating the internal surface of the fibrous pericardium (parietal
      layer) and the heart (visceral layer) forming the pericardial space. Between
      these two layers a small amount of fluid exists that is called pericardial fluid.
      The pericardial fluid is a product of ultrafiltration and is considered to be
      drained by lymphatic capillary bed mainly. Under normal conditions it provides
      lubrication during heart beating while the mesothelial cells that line the
      membrane may also have a role in the absorption of the pericardial fluid along
      with the pericardial lymphatics. Here, we provide a review of the the current
      literature regarding the physiology of the pericardial space and the regulation
      of pericardial fluid turnover and highlight the areas that need to be further
      investigated. 

PMID- 25852565
TI  - Leucine minimizes denervation-induced skeletal muscle atrophy of rats through
      akt/mtor signaling pathways.
AB  - The aim of the present study was to evaluate the effect of leucine treatment
      (0.30 mM) on muscle weight and signaling of myoproteins related to synthesis and
      degradation pathways of soleus muscle following seven days of complete sciatic
      nerve lesion. Wistar rats (n = 24) of 3-4 months of age (192 +/- 23 g) were used.
      The animals were randomly distributed into four experimental groups (n =
      6/group): control, treated with leucine (L), denervated (D) and denervated
      treated with leucine (DL). Dependent measures were proteins levels of AKT, AMPK,
      mTOR, and ACC performed by Western blot. Leucine induced a reduction in the
      phosphorylation of AMPK (p < 0.05) by 16% in the L and by 68% in the DL groups as
      compared with control group. Denervation increased AMPK by 24% in the D group as
      compared with the control group (p < 0.05). AKT was also modulated by denervation
      and leucine treatment, highlighted by the elevation of AKT phosphorylation in the
      D (65%), L (98%) and DL (146%) groups as compared with the control group (p <
      0.05). AKT phosphorylation was 49% higher in the D group as compared with the DL
      group. Furthermore, denervation decreased mTOR phosphorylation by 29% in the D
      group as compared with the control group. However, leucine treatment induced an
      increase of 49% in the phosphorylation of mTOR in the L group as compared with
      the control group, and an increase of 154% in the DL as compared with the D group
      (p < 0.05). ACC phosphorylation was 20% greater in the D group than the control
      group. Furthermore, ACC in the soleus was 22% lower in the in the L group and 50%
      lower in the DL group than the respective control group (p < 0.05). In
      conclusion, leucine treatment minimized the deleterious effects of denervation on
      rat soleus muscle by increasing anabolic (AKT and mTOR) and decreasing catabolic
      (AMPK) pathways. These results may be interesting for muscle recovery following
      acute denervation, which may contribute to musculoskeletal rehabilitation after
      denervation. 

PMID- 25852566
TI  - Novel insights into mechanisms for Pak1-mediated regulation of cardiac Ca(2+)
      homeostasis.
AB  - A series of recent studies report novel roles for Pak1, a key member of the
      highly conserved family of serine-threonine protein kinases regulated by Ras
      related small G-proteins, Cdc42/Rac1, in cardiac physiology and cardioprotection.
      Previous studies had identified Pak1 in the regulation of hypertrophic remodeling
      that could potentially lead to heart failure. This article provides a review of
      more recent findings on the roles of Pak1 in cardiac Ca(2+) homeostasis. These
      findings identified crucial roles for Pak1 in cardiomyocyte Ca(2+) handling and
      demonstrated that it functions through unique mechanisms involving regulation of
      the post-transcriptional activity of key Ca(2+)-handling proteins, including the
      expression of Ca(2+)-ATPase SERCA2a, along with the speculative possibility of an
      involvement in the maintenance of transverse (T)-tubular structure. They
      highlight important regulatory functions of Pak1 in Ca(2+) homeostasis in cardiac
      cells, and identify novel potential therapeutic strategies directed at
      manipulation of Pak1 signaling for the management of cardiac disease,
      particularly heart failure. 

PMID- 25852567
TI  - Abnormal calcium homeostasis in heart failure with preserved ejection fraction is
      related to both reduced contractile function and incomplete relaxation: an
      electromechanically detailed biophysical modeling study.
AB  - Heart failure with preserved ejection fraction (HFpEF) accounts for about 50% of
      heart failure cases. It has features of incomplete relaxation and increased
      stiffness of the left ventricle. Studies from clinical electrophysiology and
      animal experiments have found that HFpEF is associated with impaired calcium
      homeostasis, ion channel remodeling and concentric left ventricle hypertrophy
      (LVH). However, it is still unclear how the abnormal calcium homeostasis, ion
      channel and structural remodeling affect the electro-mechanical dynamics of the
      ventricles. In this study we have developed multiscale models of the human left
      ventricle from single cells to the 3D organ, which take into consideration HFpEF
      induced changes in calcium handling, ion channel remodeling and concentric LVH.
      Our simulation results suggest that at the cellular level, HFpEF reduces the
      systolic calcium level resulting in a reduced systolic contractile force, but
      elevates the diastolic calcium level resulting in an abnormal residual diastolic
      force. In our simulations, these abnormal electro-mechanical features of the
      ventricular cells became more pronounced with the increase of the heart rate.
      However, at the 3D organ level, the ejection fraction of the left ventricle was
      maintained due to the concentric LVH. The simulation results of this study mirror
      clinically observed features of HFpEF and provide new insights toward the
      understanding of the cellular bases of impaired cardiac electromechanical
      functions in heart failure. 

PMID- 25852570
TI  - The calcium-ROS-pH triangle and mitochondrial permeability transition: challenges
      to mimic cardiac ischemia-reperfusion.

PMID- 25852571
TI  - Commentary on: "Tissue engineering: How to build a heart".

PMID- 25852569
TI  - TGF-beta/Smad signaling in renal fibrosis.
AB  - TGF-beta (transforming growth factor-beta) is well identified as a central
      mediator in renal fibrosis. TGF-beta initiates canonical and non-canonical
      pathways to exert multiple biological effects. Among them, Smad signaling is
      recognized as a major pathway of TGF-beta signaling in progressive renal
      fibrosis. During fibrogenesis, Smad3 is highly activated, which is associated
      with the down-regulation of an inhibitory Smad7 via an ubiquitin E3-ligases
      dependent degradation mechanism. The equilibrium shift between Smad3 and Smad7
      leads to accumulation and activation of myofibroblasts, overproduction of ECM
      (extracellular matrix), and reduction in ECM degradation in the diseased kidney.
      Therefore, overexpression of Smad7 has been shown to be a therapeutic agent for
      renal fibrosis in various models of kidney diseases. In contrast, another
      downstream effecter of TGF-beta/Smad signaling pathway, Smad2, exerts its renal
      protective role by counter-regulating the Smad3. Furthermore, recent studies
      demonstrated that Smad3 mediates renal fibrosis by down-regulating miR-29 and miR
      200 but up-regulating miR-21 and miR-192. Thus, overexpression of miR-29 and miR
      200 or down-regulation of miR-21 and miR-192 is capable of attenuating Smad3
      mediated renal fibrosis in various mouse models of chronic kidney diseases (CKD).
      Taken together, TGF-beta/Smad signaling plays an important role in renal
      fibrosis. Targeting TGF-beta/Smad3 signaling may represent a specific and
      effective therapy for CKD associated with renal fibrosis. 

PMID- 25852568
TI  - Is it time to turn our attention toward central mechanisms for post-exertional
      recovery strategies and performance?
AB  - Key PointsCentral fatigue is accepted as a contributor to overall athletic
      performance, yet little research directly investigates post-exercise recovery
      strategies targeting the brainCurrent post-exercise recovery strategies likely
      impact on the brain through a range of mechanisms, but improvements to these
      strategies is neededResearch is required to optimize post-exercise recovery with
      a focus on the brain Post-exercise recovery has largely focused on peripheral
      mechanisms of fatigue, but there is growing acceptance that fatigue is also
      contributed to through central mechanisms which demands that attention should be
      paid to optimizing recovery of the brain. In this narrative review we assemble
      evidence for the role that many currently utilized recovery strategies may have
      on the brain, as well as potential mechanisms for their action. The review
      provides discussion of how common nutritional strategies as well as physical
      modalities and methods to reduce mental fatigue are likely to interact with the
      brain, and offer an opportunity for subsequent improved performance. We aim to
      highlight the fact that many recovery strategies have been designed with the
      periphery in mind, and that refinement of current methods are likely to provide
      improvements in minimizing brain fatigue. Whilst we offer a number of
      recommendations, it is evident that there are many opportunities for improving
      the research, and practical guidelines in this area. 

PMID- 25852572
TI  - AMP-activated protein kinase controls exercise training- and AICAR-induced
      increases in SIRT3 and MnSOD.
AB  - The mitochondrial protein deacetylase sirtuin (SIRT) 3 may mediate exercise
      training-induced increases in mitochondrial biogenesis and improvements in
      reactive oxygen species (ROS) handling. We determined the requirement of AMP
      activated protein kinase (AMPK) for exercise training-induced increases in
      skeletal muscle abundance of SIRT3 and other mitochondrial proteins. Exercise
      training for 6.5 weeks increased SIRT3 (p < 0.01) and superoxide dismutase 2
      (MnSOD; p < 0.05) protein abundance in quadriceps muscle of wild-type (WT; n = 13
      15), but not AMPK alpha2 kinase dead (KD; n = 12-13) mice. We also observed a
      strong trend for increased MnSOD abundance in exercise-trained skeletal muscle of
      healthy humans (p = 0.051; n = 6). To further elucidate a role for AMPK in
      mediating these effects, we treated WT (n = 7-8) and AMPK alpha2 KD (n = 7-9)
      mice with 5-amino-1-beta-D-ribofuranosyl-imidazole-4-carboxamide (AICAR). Four
      weeks of daily AICAR injections (500 mg/kg) resulted in AMPK-dependent increases
      in SIRT3 (p < 0.05) and MnSOD (p < 0.01) in WT, but not AMPK alpha2 KD mice. We
      also tested the effect of repeated AICAR treatment on mitochondrial protein
      levels in mice lacking the transcriptional coactivator peroxisome proliferator
      activated receptor gamma-coactivator 1alpha (PGC-1alpha KO; n = 9-10). Skeletal
      muscle SIRT3 and MnSOD protein abundance was reduced in sedentary PGC-1alpha KO
      mice (p < 0.01) and AICAR-induced increases in SIRT3 and MnSOD protein abundance
      was only observed in WT mice (p < 0.05). Finally, the acetylation status of SIRT3
      target lysine residues on MnSOD (K122) or oligomycin-sensitivity conferring
      protein (OSCP; K139) was not altered in either mouse or human skeletal muscle in
      response to acute exercise. We propose an important role for AMPK in regulating
      mitochondrial function and ROS handling in skeletal muscle in response to
      exercise training. 

PMID- 25852573
TI  - Chemical coding and chemosensory properties of cholinergic brush cells in the
      mouse gastrointestinal and biliary tract.
AB  - The mouse gastro-intestinal and biliary tract mucosal epithelia harbor choline
      acetyltransferase (ChAT)-positive brush cells with taste cell-like traits. With
      the aid of two transgenic mouse lines that express green fluorescent protein
      (EGFP) under the control of the ChAT promoter (EGFP (ChAT) ) and by using in situ
      hybridization and immunohistochemistry we found that EGFP (ChAT) cells were
      clustered in the epithelium lining the gastric groove. EGFP (ChAT) cells were
      numerous in the gall bladder and bile duct, and found scattered as solitary cells
      along the small and large intestine. While all EGFP (ChAT) cells were also ChAT
      positive, expression of the high-affinity choline transporter (ChT1) was never
      detected. Except for the proximal colon, EGFP (ChAT) cells also lacked detectable
      expression of the vesicular acetylcholine transporter (VAChT). EGFP (ChAT) cells
      were found to be separate from enteroendocrine cells, however they were all
      immunoreactive for cytokeratin 18 (CK18), transient receptor potential melastatin
      like subtype 5 channel (TRPM5), and for cyclooxygenases 1 (COX1) and 2 (COX2).
      The ex vivo stimulation of colonic EGFP (ChAT) cells with the bitter substance
      denatonium resulted in a strong increase in intracellular calcium, while in other
      epithelial cells such an increase was significantly weaker and also timely
      delayed. Subsequent stimulation with cycloheximide was ineffective in both cell
      populations. Given their chemical coding and chemosensory properties, EGFP (ChAT)
      brush cells thus may have integrative functions and participate in induction of
      protective reflexes and inflammatory events by utilizing ACh and prostaglandins
      for paracrine signaling. 

PMID- 25852574
TI  - Demystifying cognitive science: explaining cognition through network-based
      modeling.

PMID- 25852577
TI  - Socio-Economic Status Determines Risk of Receptive Syringe Sharing Behaviors
      among Iranian Drug Injectors; A National Study.
AB  - BACKGROUND: Although needle and syringe sharing is one of the main routs of
      transmission of HIV in several countries in the middle east, very little is known
      about how socio-economic status of injecting drug users (IDUs) is linked to the
      receptive syringe sharing behaviors in these countries. AIM: To study socio
      economic correlates of receptive needle and syringe sharing among IDUs in Iran.
      METHODS: The study used data from the Unhide Risk Study, a national survey of
      IDUs. This study sampled 636 IDUs (91% male) via snowball sampling from eight
      provinces in Iran in 2009. Socio-demographic and drug use characteristics were
      collected. We used a logistic regression to determine factors associated with
      receptive needle and syringe sharing during the past 6 months. RESULTS: From 636
      IDUs enrolled in this study, 68% (n = 434) reported receptive needle and syringe
      sharing behaviors in the past 6 months. Odds of receptive needle and syringe
      sharing in the past 6 months was lower among IDUs who were male [odds ratios (OR)
      = 0.29, 95% confidence interval (CI) = 0.12-0.70], had higher education (OR =
      0.74, 95% CI = 0.64-0.86) but higher among those who were unemployed (OR = 4.05,
      95% CI = 1.50-10.94), and were single (OR = 1.47, 95% CI = 1.02-2.11).
      CONCLUSION: This study presented factors associated with risk of receptive needle
      and syringe sharing among Iranian IDUs. This information may be used for HIV
      prevention and harm reduction purposes. Socio-economic status of Iranian IDUs may
      be closely linked to high-risk injecting behaviors among them.

PMID- 25852575
TI  - Organization and dynamics of SNARE proteins in the presynaptic membrane.
AB  - Our view of the lateral organization of lipids and proteins in the plasma
      membrane has evolved substantially in the last few decades. It is widely accepted
      that many, if not all, plasma membrane proteins and lipids are organized in
      specific domains. These domains vary widely in size, composition, and stability,
      and they represent platforms governing diverse cell functions. The presynaptic
      plasma membrane is a well-studied example of a membrane which undergoes
      rearrangements, especially during exo- and endocytosis. Many proteins and lipids
      involved in presynaptic function are known, and major efforts have been made to
      understand their spatial organization and dynamics. Here, we focus on the
      mechanisms underlying the organization of SNAREs, the key proteins of the fusion
      machinery, in distinct domains, and we discuss the functional significance of
      these clusters. 

PMID- 25852576
TI  - Tetraspanins as therapeutic targets in hematological malignancy: a concise
      review.
AB  - Tetraspanins belong to a family of transmembrane proteins which play a major role
      in the organization of the plasma membrane. While all immune cells express
      tetraspanins, most of these are present in a variety of other cell types. There
      are a select few, such as CD37 and CD53, which are restricted to hematopoietic
      lineages. Tetraspanins associate with numerous partners involved in a diverse set
      of biological processes, including cell activation, survival, proliferation,
      adhesion, and migration. The historical view has assigned them a scaffolding
      role, but recent discoveries suggest some tetraspanins can directly participate
      in signaling through interactions with cytoplasmic proteins. Given their
      potential roles in supporting tumor survival and immune evasion, an improved
      understanding of tetraspanin activity could prove clinically valuable. This
      review will focus on emerging data in the study of tetraspanins, advances in the
      clinical development of anti-CD37 therapeutics, and the future prospects of
      targeting tetraspanins in hematological malignancy. 

PMID- 25852578
TI  - "Diagnosis by behavioral observation" home-videosomnography - a rigorous
      ethnographic approach to sleep of children with neurodevelopmental conditions.
AB  - INTRODUCTION: Advanced video technology is available for sleep-laboratories.
      However, low-cost equipment for screening in the home setting has not been
      identified and tested, nor has a methodology for analysis of video recordings
      been suggested. METHODS: We investigated different combinations of
      hardware/software for home-videosomnography (HVS) and established a process for
      qualitative and quantitative analysis of HVS-recordings. A case vignette (HVS
      analysis for a 5.5-year-old girl with major insomnia and several co-morbidities)
      demonstrates how methodological considerations were addressed and how HVS added
      value to clinical assessment. RESULTS: We suggest an "ideal set of
      hardware/software" that is reliable, affordable (~$500) and portable (=2.8 kg) to
      conduct non-invasive HVS, which allows time-lapse analyses. The equipment
      consists of a net-book, a camera with infrared optics, and a video capture
      device. (1) We present an HVS-analysis protocol consisting of three steps of
      analysis at varying replay speeds: (a) basic overview and classification at 16*
      normal speed; (b) second viewing and detailed descriptions at 4-8* normal speed,
      and (c) viewing, listening, and in-depth descriptions at real-time speed. (2) We
      also present a custom software program that facilitates video analysis and note
      taking (Annotator((c))), and Optical Flow software that automatically quantifies
      movement for internal quality control of the HVS-recording. The case vignette
      demonstrates how the HVS-recordings revealed the dimension of insomnia caused by
      restless legs syndrome, and illustrated the cascade of symptoms, challenging
      behaviors, and resulting medications. CONCLUSION: The strategy of using HVS,
      although requiring validation and reliability testing, opens the floor for a new
      "observational sleep medicine," which has been useful in describing discomfort
      related behavioral movement patterns in patients with communication difficulties
      presenting with challenging/disruptive sleep/wake behaviors.

PMID- 25852580
TI  - Using historical accounts of harpsichord touch to empirically investigate the
      production and perception of dynamics on the 1788 Taskin.
AB  - This article investigates the extent of production and perception of dynamic
      differences on a French historical harpsichord, extensively revised in 1788 by
      Pascal Taskin. A historical review reports on the descriptions of two different
      types of touch found in treatises of the 18th century. These two touches
      (loud/struck and soft/pressed) were used to perform single tones on the lower,
      upper, peau de buffle (PDB) registers (the last of which Taskin is credited with
      having invented) and the coupled 8-foot registers to investigate differences in
      dynamics. Acoustic measurements show varied differences of up to 11 dB for the
      two types of touch over different pitches in each register. The strongest
      difference is measured in the first harmonic of note F2 on the PDB. A listening
      experiment was conducted to test whether these differences are perceivable.
      Participants performed a discrimination task using pairs of single tones.
      Participants were able to perform significantly better than chance in correctly
      identifying whether pairs of single tones were same or different with respect to
      loudness [t(24) = 12.01, p < 0.001]. Accuracies were influenced by pitch and
      register, the PDB providing the strongest accuracies over the four registers
      tested. 

PMID- 25852579
TI  - Could vagus nerve stimulation target hippocampal hyperactivity to improve
      cognition in schizophrenia?

PMID- 25852581
TI  - Impact of dialect use on a basic component of learning to read.
AB  - Can some black-white differences in reading achievement be traced to differences
      in language background? Many African American children speak a dialect that
      differs from the mainstream dialect emphasized in school. We examined how use of
      alternative dialects affects decoding, an important component of early reading
      and marker of reading development. Behavioral data show that use of the
      alternative pronunciations of words in different dialects affects reading aloud
      in developing readers, with larger effects for children who use more African
      American English (AAE). Mechanisms underlying this effect were explored with a
      computational model, investigating factors affecting reading acquisition. The
      results indicate that the achievement gap may be due in part to differences in
      task complexity: children whose home and school dialects differ are at greater
      risk for reading difficulties because tasks such as learning to decode are more
      complex for them. 

PMID- 25852582
TI  - Perceiving fingers in single-digit arithmetic problems.
AB  - In this study, we investigate in children the neural underpinnings of finger
      representation and finger movement involved in single-digit arithmetic problems.
      Evidence suggests that finger representation and finger-based strategies play an
      important role in learning and understanding arithmetic. Because different
      operations rely on different networks, we compared activation for subtraction and
      multiplication problems in independently localized finger somatosensory and motor
      areas and tested whether activation was related to skill. Brain activations from
      children between 8 and 13 years of age revealed that only subtraction problems
      significantly activated finger motor areas, suggesting reliance on finger-based
      strategies. In addition, larger subtraction problems yielded greater
      somatosensory activation than smaller problems, suggesting a greater reliance on
      finger representation for larger numerical values. Interestingly, better
      performance in subtraction problems was associated with lower activation in the
      finger somatosensory area. Our results support the importance of fine-grained
      finger representation in arithmetical skill and are the first neurological
      evidence for a functional role of the somatosensory finger area in proficient
      arithmetical problem solving, in particular for those problems requiring quantity
      manipulation. From an educational perspective, these results encourage
      investigating whether different finger-based strategies facilitate arithmetical
      understanding and encourage educational practices aiming at integrating finger
      representation and finger-based strategies as a tool for instilling stronger
      numerical sense. 

PMID- 25852583
TI  - Up or down? Reading direction influences vertical counting direction in the
      horizontal plane - a cross-cultural comparison.
AB  - Most adults and children in cultures where reading text progresses from left to
      right also count objects from the left to the right side of space. The reverse is
      found in cultures with a right-to-left reading direction. The current set of
      experiments investigated whether vertical counting in the horizontal plane is
      also influenced by reading direction. Participants were either from a left-to
      right reading culture (UK) or from a mixed (left-to-right and top-to-bottom)
      reading culture (Hong Kong). In Experiment 1, native English-speaking children
      and adults and native Cantonese-speaking children and adults performed three
      object counting tasks. Objects were presented flat on a table in a horizontal,
      vertical, and square display. Independent of culture, the horizontal array was
      mostly counted from left to right. While the majority of English-speaking
      children counted the vertical display from bottom to top, the majority of the
      Cantonese-speaking children as well as both Cantonese- and English-speaking
      adults counted the vertical display from top to bottom. This pattern was
      replicated in the counting pattern for squares: all groups except the English
      speaking children started counting with the top left coin. In Experiment 2,
      Cantonese-speaking adults counted a square array of objects after they read a
      text presented to them either in left-to-right or in top-to-bottom reading
      direction. Most Cantonese-speaking adults started counting the array by moving
      horizontally from left to right. However, significantly more Cantonese-speaking
      adults started counting with a top-to-bottom movement after reading the text
      presented in a top-to-bottom reading direction than in a left-to-right reading
      direction. Our results show clearly that vertical counting in the horizontal
      plane is influenced by longstanding as well as more recent experience of reading
      direction. 

PMID- 25852584
TI  - Arbitrary numbers counter fair decisions: trails of markedness in card
      distribution.
AB  - Converging evidence from controlled experiments suggests that the mere processing
      of a number and its attributes such as value or parity might affect free choice
      decisions between different actions. For example the spatial numerical
      associations of response codes (SNARC) effect indicates the magnitude of a digit
      to be associated with a spatial representation and might therefore affect spatial
      response choices (i.e., decisions between a "left" and a "right" option). At the
      same time, other (linguistic) features of a number such as parity are embedded
      into space and might likewise prime left or right responses through feature words
      [odd or even, respectively; markedness association of response codes (MARC)
      effect]. In this experiment we aimed at documenting such influences in a natural
      setting. We therefore assessed number-space and parity-space association effects
      by exposing participants to a fair distribution task in a card playing scenario.
      Participants drew cards, read out loud their number values, and announced their
      response choice, i.e., dealing it to a left vs. right player, indicated by
      Playmobil characters. Not only did participants prefer to deal more cards to the
      right player, the card's digits also affected response choices and led to a
      slightly but systematically unfair distribution, supported by a regular SNARC
      effect and counteracted by a reversed MARC effect. The experiment demonstrates
      the impact of SNARC- and MARC-like biases in free choice behavior through verbal
      and visual numerical information processing even in a setting with high external
      validity. 

PMID- 25852585
TI  - Regulatory focus and generalized trust: the impact of prevention-focused self
      regulation on trusting others.
AB  - The current research suggests that taking self-regulatory mechanisms into account
      provides insights regarding individuals' responses to threats in social
      interactions. In general, based on the notion that a prevention-focused
      orientation of self-regulation is associated with a need for security and a
      vigilant tendency to avoid losses and other types of negative events we advocate
      that a prevention-focused orientation, both as a disposition as well as a
      situationally induced state, lowers generalized trust, thus hindering cooperation
      within social interactions that entail threats. Specifically, we found that the
      more individuals' habitual self-regulatory orientation is dominated by a
      prevention focus, the less likely they are to score high on a self-report measure
      of generalized trust (Study 1), and to express trust in a trust game paradigm as
      manifested in lower sums of transferred money (Studies 2 and 3). Similar findings
      were found when prevention focus was situationally manipulated (Study 4).
      Finally, one possible factor underlying the impact of prevention-focused self
      regulation on generalized trust was demonstrated as individuals with a special
      sensitivity to negative information were significantly affected by a subtle
      prevention focus manipulation (versus control condition) in that they reacted
      with reduced trust in the trust game (Study 5). In sum, the current findings
      document the crucial relevance of self-regulatory orientations as conceptualized
      in regulatory focus theory regarding generalized trust and responses to threats
      within a social interaction. The theoretical and applied implications of the
      findings are discussed. 

PMID- 25852586
TI  - Catecholamine responses to virtual combat: implications for post-traumatic stress
      and dimensions of functioning.
AB  - Posttraumatic stress disorder (PTSD) symptoms can result in functional impairment
      among service members (SMs), even in those without a clinical diagnosis. The
      variability in outcomes may be related to underlying catecholamine mechanisms.
      Individuals with PTSD tend to have elevated basal catecholamine levels, though
      less is known regarding catecholamine responses to trauma-related stimuli. We
      assessed whether catecholamine responses to a virtual combat environment impact
      the relationship between PTSD symptom clusters and elements of functioning.
      Eighty-seven clinically healthy SMs, within 2 months after deployment to Iraq or
      Afghanistan, completed self-report measures, viewed virtual-reality (VR) combat
      sequences, and had sequential blood draws. Norepinephrine responses to VR combat
      exposure moderated the relationship between avoidance symptoms and scales of
      functioning including physical functioning, physical-role functioning, and
      vitality. Among those with high levels of avoidance, norepinephrine change was
      inversely associated with functional status, whereas a positive correlation was
      observed for those with low levels of avoidance. Our findings represent a novel
      use of a virtual environment to display combat-related stimuli to returning SMs
      to elucidate mind-body connections inherent in their responses. The insight
      gained improves our understanding of post-deployment symptoms and quality of life
      in SMs and may facilitate enhancements in treatment. Further research is needed
      to validate these findings in other populations and to define the implications
      for treatment effectiveness. 

PMID- 25852587
TI  - Disagreeing in context.
AB  - This paper argues for contextualism about predicates of personal taste and
      evaluative predicates in general, and offers a proposal of how apparently
      resilient disagreements are to be explained. The present proposal is
      complementary to others that have been made in the recent literature. Several
      authors, for instance (Lopez de Sa, 2008; Sundell, 2011; Huvenes, 2012; Marques
      and Garcia-Carpintero, 2014; Marques, 2014a), have recently defended semantic
      contextualism for those kinds of predicates from the accusation that it faces the
      problem of lost disagreement. These authors have proposed that a proper account
      of the resilient disagreement in the cases studied is to be achieved by an appeal
      to pragmatic processes, and to conflicting non-doxastic attitudes. It is argued
      here that the existing contextualist solutions are incomplete as they stand, and
      are subject to objections because of this. A supplementation of contextualism is
      offered, together with an explanation of why failed presuppositions of
      commonality (Lopez de Sa), disputes over the appropriateness of a contextually
      salient standard (Sundell), and differences in non-doxastic attitudes (Sundell,
      Huvenes, Marques, and Garcia-Carpintero) give rise to conflicts. This paper
      claims that conflicts of attitudes are the reason why people still have
      impressions of disagreement in spite of failed commonality presuppositions, that
      those conflicts drive metalinguistic disputes over the selection of appropriate
      standards, and hence conflicting non-doxastic attitudes demand an explanation
      that is independent of those context dependent pragmatic processes. The paper
      further argues that the missing explanation is 2-fold: first, disagreement
      prevails where the properties expressed by taste and value predicates are
      response-dependent properties, and, secondly, it prevails where those response
      dependent properties are involved in evolved systems of coordination that respond
      to evolutionarily recurrent situations. 

PMID- 25852588
TI  - The relationship between deferred imitation, associative memory, and
      communication in 14-months-old children. Behavioral and electrophysiological
      indices.
AB  - The present study combines behavioral observations of memory (deferred imitation,
      DI, after a brief delay of 30 min and after a long delay of 2-3 weeks) and
      electrophysiological (event-related potentials, ERPs) measures of associative
      memory, as well as parental reports of non-verbal and verbal communication in
      sixteen 14-months-old children. Results show that for DI, the children remembered
      the stimulus after the brief but not after the long delay. There was a clear
      electrophysiological response indicating associative memory. Furthermore, a
      correlation between DI and ERP suggests that both measures of memory (DI and
      associative memory) tap into similar mechanisms in 14-months-old children. There
      was also a statistically significant relation between parental report of
      receptive (verbal) language and the ERP, showing an association between receptive
      language skills and associative memory. 

PMID- 25852589
TI  - The complex duration perception of emotional faces: effects of face direction.
AB  - The perceived duration of emotional face stimuli strongly depends on the
      expressed emotion. But, emotional faces also differ regarding a number of other
      features like gaze, face direction, or sex. Usually, these features have been
      controlled by only using pictures of female models with straight gaze and face
      direction. Doi and Shinohara (2009) reported that an overestimation of angry
      faces could only be found when the model's gaze was oriented toward the observer.
      We aimed at replicating this effect for face direction. Moreover, we explored the
      effect of face direction on the duration perception sad faces. Controlling for
      the sex of the face model and the participant, female and male participants rated
      the duration of neutral, angry, and sad face stimuli of both sexes photographed
      from different perspectives in a bisection task. In line with current findings,
      we report a significant overestimation of angry compared to neutral face stimuli
      that was modulated by face direction. Moreover, the perceived duration of sad
      face stimuli did not differ from that of neutral faces and was not influenced by
      face direction. Furthermore, we found that faces of the opposite sex appeared to
      last longer than those of the same sex. This outcome is discussed with regards to
      stimulus parameters like the induced arousal, social relevance, and an
      evolutionary context. 

PMID- 25852590
TI  - Empathy and nonattachment independently predict peer nominations of prosocial
      behavior of adolescents.
AB  - There is a plethora of research showing that empathy promotes prosocial behavior
      among young people. We examined a relatively new construct in the mindfulness
      literature, nonattachment, defined as a flexible way of relating to one's
      experiences without clinging to or suppressing them. We tested whether
      nonattachment could predict prosociality above and beyond empathy. Nonattachment
      implies high cognitive flexibility and sufficient mental resources to step out of
      excessive self-cherishing to be there for others in need. Multilevel Poisson
      models using a sample of 15-year olds (N = 1831) showed that empathy and
      nonattachment independently predicted prosocial behaviors of helpfulness and
      kindness, as judged by same-sex and opposite-sex peers, except for when boys
      nominated girls. The effects of nonattachment remained substantial in more
      conservative models including self-esteem and peer nominations of liking. 

PMID- 25852591
TI  - Number word structure in first and second language influences arithmetic skills.
AB  - Languages differ in how they represent numerical information, and specifically
      whether the verbal notation of numbers follows the same order as the symbolic
      notation (in non-inverted languages, e.g., Hebrew, "25, twenty-five") or whether
      the two notations diverge (in inverted languages, e.g., Arabic, "25, five-and
      twenty"). We examined how the structure of number-words affects how arithmetic
      operations are processed by bilingual speakers of an inverted and a non-inverted
      language. We examined Arabic-Hebrew bilinguals' performance in the first
      language, L1 (inverted) and in the second language, L2 (non-inverted). Their
      performance was compared to that of Hebrew L1 speakers, who do not speak an
      inverted language. Participants judged the accuracy of addition problems
      presented aurally in L1, aurally in L2 or in visual symbolic notation. Problems
      were presented such that they matched or did not match the structure of number
      words in the language. Arabic-Hebrew bilinguals demonstrated both flexibility in
      processing and adaptation to the language of aural-verbal presentation - they
      were more accurate for the inverted order of presentation in Arabic, but more
      accurate for non-inverted order of presentation in Hebrew, thus exhibiting the
      same pattern found for native Hebrew speakers. In addition, whereas native Hebrew
      speakers preferred the non-inverted order in visual symbolic presentation as
      well, the Arabic-Hebrew bilinguals showed enhanced flexibility, without a
      significant preference for one order over the other, in either speed or accuracy.
      These findings suggest that arithmetic processing is sensitive to the linguistic
      representations of number words. Moreover, bilinguals exposed to inverted and non
      inverted languages showed influence of both systems, and enhanced flexibility in
      processing. Thus, the L1 does not seem to have exclusive power in shaping
      numerical mental representations, but rather the system remains open to
      influences from a later learned L2. 

PMID- 25852592
TI  - New drugs and polydrug use: implications for clinical psychology.

PMID- 25852593
TI  - Turn-timing in signed conversations: coordinating stroke-to-stroke turn
      boundaries.
AB  - In spoken interactions, interlocutors carefully plan, and time their utterances,
      minimizing gaps and overlaps between consecutive turns. Cross-linguistic
      comparison has indicated that spoken languages vary only minimally in terms of
      turn-timing, and language acquisition research has shown pre-linguistic vocal
      turn-taking in the first half year of life. These observations suggest that the
      turn-taking system may provide a fundamental basis for our linguistic capacities.
      The question remains, however, to what extent our capacity for rapid turn-taking
      is determined by modality constraints. The avoidance of overlapping turns could
      be motivated by the difficulty of hearing and speaking at the same time. If so,
      turn-taking in sign might show greater toleration for overlap. Alternatively,
      signed conversations may show a similar distribution of turn-timing as spoken
      languages, thus avoiding both gaps and overlaps. To address this question we look
      at turn-timing in question-answer sequences in spontaneous conversations of Sign
      Language of the Netherlands. The findings indicate that although there is
      considerable overlap in two or more signers' articulators in conversation, when
      proper allowance is made for onset preparation, post-utterance retraction and the
      intentional holding of signs for response, turn-taking latencies in sign look
      remarkably like those reported for spoken language. This is consistent with the
      possibility that, at least with regard to responses to questions, speakers and
      signers follow similar time courses in planning and producing their utterances in
      on-going conversation. This suggests that turn-taking systems may well be a
      shared cognitive infrastructure underlying all modern human languages, both
      spoken and signed. 

PMID- 25852595
TI  - The precedence of syntax in the rapid emergence of human language in evolution as
      defined by the integration hypothesis.
AB  - Our core hypothesis is that the emergence of human language arose very rapidly
      from the linking of two pre-adapted systems found elsewhere in the animal world
      an expression system, found, for example, in birdsong, and a lexical system,
      suggestively found in non-human primate calls (Miyagawa et al., 2013, 2014). We
      challenge the view that language has undergone a series of gradual changes-or a
      single preliminary protolinguistic stage-before achieving its full character. We
      argue that a full-fledged combinatorial operation Merge triggered the integration
      of these two pre-adapted systems, giving rise to a fully developed language. This
      goes against the gradualist view that there existed a structureless,
      protolinguistic stage, in which a rudimentary proto-Merge operation generated
      internally flat words. It is argued that compounds in present-day language are a
      fossilized form of this prior stage, a point which we will question. 

PMID- 25852594
TI  - Does long-term object priming depend on the explicit detection of object identity
      at encoding?
AB  - It is currently unclear whether objects have to be explicitly identified at
      encoding for reliable behavioral long-term object priming to occur. We conducted
      two experiments that investigated long-term object and non-object priming using a
      selective-attention encoding manipulation that reduces explicit object
      identification. In Experiment 1, participants either counted dots flashed within
      an object picture (shallow encoding) or engaged in an animacy task (deep
      encoding) at study, whereas, at test, they performed an object-decision task.
      Priming, as measured by reaction times (RTs), was observed for both types of
      encoding, and was of equivalent magnitude. In Experiment 2, non-object priming
      (faster RTs for studied relative to unstudied non-objects) was also obtained
      under the same selective-attention encoding manipulation as in Experiment 1, and
      the magnitude of the priming effect was equivalent between experiments. In
      contrast, we observed a linear decrement in recognition memory accuracy across
      conditions (deep encoding of Experiment 1 > shallow encoding Experiment 1 >
      shallow encoding of Experiment 2), suggesting that priming was not contaminated
      by explicit memory strategies. We argue that our results are more consistent with
      the identification/production framework than the perceptual/conceptual
      distinction, and we conclude that priming of pictures largely ignored at encoding
      can be subserved by the automatic retrieval of two types of instances: one at the
      motor level and another at an object-decision level. 

PMID- 25852596
TI  - LIFESPAN: A tool for the computer-aided design of longitudinal studies.
AB  - Researchers planning a longitudinal study typically search, more or less
      informally, a multivariate space of possible study designs that include
      dimensions such as the hypothesized true variance in change, indicator
      reliability, the number and spacing of measurement occasions, total study time,
      and sample size. The main search goal is to select a research design that best
      addresses the guiding questions and hypotheses of the planned study while heeding
      applicable external conditions and constraints, including time, money,
      feasibility, and ethical considerations. Because longitudinal study selection
      ultimately requires optimization under constraints, it is amenable to the general
      operating principles of optimization in computer-aided design. Based on power
      equivalence theory (MacCallum et al., 2010; von Oertzen, 2010), we propose a
      computational framework to promote more systematic searches within the study
      design space. Starting with an initial design, the proposed framework generates a
      set of alternative models with equal statistical power to detect hypothesized
      effects, and delineates trade-off relations among relevant parameters, such as
      total study time and the number of measurement occasions. We present LIFESPAN
      (Longitudinal Interactive Front End Study Planner), which implements this
      framework. LIFESPAN boosts the efficiency, breadth, and precision of the search
      for optimal longitudinal designs. Its initial version, which is freely available
      at http://www.brandmaier.de/lifespan, is geared toward the power to detect
      variance in change as specified in a linear latent growth curve model. 

PMID- 25852598
TI  - How to enhance the well-being of healthcare service providers and their patients?
      A mindfulness proposal.

PMID- 25852597
TI  - The neural substrates of response inhibition to negative information across
      explicit and implicit tasks in GAD patients: electrophysiological evidence from
      an ERP study.
AB  - BACKGROUND: It has been established that the inability to inhibit a response to
      negative stimuli is the genesis of anxiety. However, the neural substrates of
      response inhibition to sad faces across explicit and implicit tasks in general
      anxiety disorder (GAD) patients remain unclear. METHODS: Electrophysiological
      data were recorded when subjects performed two modified emotional go/no-go tasks
      in which neutral and sad faces were presented: one task was explicit (emotion
      categorization), and the other task was implicit (gender categorization).
      RESULTS: In the explicit task, electrophysiological evidence showed decreased
      amplitudes of no-go/go difference waves at the N2 interval in the GAD group
      compared to the control group. However, in the implicit task, the amplitudes of
      no-go/go difference waves at the N2 interval showed a reversed trend. Source
      localization analysis on no-go/N2 components revealed a decreased current source
      density (CSD) in the right dorsal lateral prefrontal cortex in GAD individuals
      relative to controls. In the implicit task, the left superior temporal gyrus and
      the left inferior parietal lobe showed enhanced activation in GAD individuals and
      may compensate for the dysfunction of the right dorsal lateral prefrontal cortex.
      CONCLUSION: These findings indicated that the processing of response inhibition
      to socially sad faces in GAD individuals was interrupted in the explicit task.
      However, this processing was preserved in the implicit task. The neural
      substrates of response inhibition to sad faces were dissociated between implicit
      and explicit tasks.

PMID- 25852599
TI  - Affective valence facilitates spatial detection on vertical axis: shorter time
      strengthens effect.
AB  - Affective concepts can be described in terms of space, which is known as the
      valence-space metaphor. Previous studies have not investigated either the
      specifics of this metaphor on the transverse and vertical axes or the time course
      of this metaphoric association. With Chinese participants, we used a spatial cue
      task to study the valence-space metaphor on the transverse (left-and-right;
      Experiment 1A) and vertical (upper-and-lower; Experiment 1B) axes. After being
      shown an affective word and asked to keep it in mind, the participants were given
      a spatial target detection task. The results revealed that the metaphoric
      association was only found on the vertical axis. More specifically, keeping a
      positive word in mind facilitated the detection of the upper target, but no such
      effect was found in the detection of the lower target. Furthermore, in Experiment
      2, we manipulated the duration of time (100, 500, and 1000 ms) between the offset
      of the affective word and the onset of the spatial target (i.e., interstimulus
      intervals, ISI), to test the dynamic time course of the valence-space metaphor on
      the vertical axis. The results showed that when ISI was 100 ms, keeping a
      positive word in mind facilitated the detection of the upper target and keeping a
      negative word in mind facilitated the detection of the lower target. However,
      when the ISI was 500 or 1000 ms, keeping a positive word in mind facilitated the
      detection of the upper target and no such effect was found in the detection of
      the lower target, indicating that ISI might be important in the valence-space
      metaphoric association. In sum, we found that the processing of affective valence
      activated the vertical spatial axis but not the transverse axis. Further, the
      association might be modulated by ISI, indicating that it may be related to
      attention allocation. 

PMID- 25852600
TI  - Children's looking preference for biological motion may be related to an affinity
      for mathematical chaos.
AB  - Recognition of biological motion is pervasive in early child development.
      Further, viewing the movement behavior of others is a primary component of a
      child's acquisition of complex, robust movement repertoires, through imitation
      and real-time coordinated action. We theorize that inherent to biological
      movements are particular qualities of mathematical chaos and complexity. We
      further posit that this character affords the rich and complex inter-dynamics
      throughout early motor development. Specifically, we explored whether children's
      preference for biological motion may be related to an affinity for mathematical
      chaos. Cross recurrence quantification analysis (cRQA) was used to investigate
      the coordination of gaze and posture with various temporal structures (periodic,
      chaotic, and aperiodic) of the motion of an oscillating visual stimulus. Children
      appear to competently perceive and respond to chaotic motion, both in rate (cRQA
      percent determinism) and duration (cRQA-maxline) of coordination. We interpret
      this to indicate that children not only recognize chaotic motion structures, but
      also have a preference for coordination with them. Further, stratification of our
      sample (by age) uncovers the suggestion that this preference may become refined
      with age. 

PMID- 25852601
TI  - Predicting who takes music lessons: parent and child characteristics.
AB  - Studies on associations between music training and cognitive abilities typically
      focus on the possible benefits of music lessons. Recent research suggests,
      however, that many of these associations stem from niche-picking tendencies,
      which lead certain individuals to be more likely than others to take music
      lessons, especially for long durations. Because the initial decision to take
      music lessons is made primarily by a child's parents, at least at younger ages,
      we asked whether individual differences in parents' personality predict young
      children's duration of training. Children between 7 and 9 years of age (N = 170)
      with varying amounts of music training completed a measure of IQ. Their parents
      provided demographic information as well as ratings of their own and their
      child's Big Five personality dimensions. Children's personality traits predicted
      duration of music training even when demographic variables and intelligence were
      held constant, replicating findings reported previously with 10- to 12-year-olds
      and 17-year-olds. A novel finding was that parents' openness-to-experience
      predicted children's duration of training, even when characteristics that
      pertained to children (demographic variables, intelligence, and personality) were
      controlled statistically. Our findings are indicative of passive and active gene
      environment correlations, whereby genetic predispositions influence the
      likelihood that a child will have certain experiences, such as music training. 

PMID- 25852602
TI  - Dreams as a source of supernatural agent concepts.
AB  - We present a theory of the creativity of dreams as well as psychopathology of
      religious delusions with respect to production of fundamental forms of religious
      cognition-specifically supernatural agent (SA) cognitions. We suggest that dream
      cognitions are particularly efficient at producing highly memorable and impactful
      experiences with SAs because dreams involve three processes that are
      prerequisites for the generation of god concepts: (1) mental simulations of
      alternative realities, (2) theory of mind attributions to the extra-natural dream
      characters and divine beings, and (3) attribution of ultimate value (exemplified
      by 'good spirit beings'), and dis-value (exemplified by demonic monsters) to the
      supernatural dream characters. Because prefrontal cortex is deactivated during
      rapid eye movements (REM) sleep agentic impulses and internally generated ideas
      are not reliably attributed to Self or dreamer. Instead an exaggerated degree of
      agency is attributed to these supernatural dream characters who are then embedded
      in stories in dreams and in myths of waking life which explain their supernatural
      abilities. These dream-based SAs are salient characters that are processed in
      sleep-related memory systems according to rules of Lleweelyn's ancient art of
      memory model and therefore more easily remembered and reflected upon during
      waking life. When REM sleep intrudes into waking consciousness, as is the case
      with some forms of schizophrenia, religious delusions are more likely to emerge. 

PMID- 25852603
TI  - Evaluation of a differentiation model of preschoolers' executive functions.
AB  - Despite the prominent role of executive functions in children's emerging
      competencies, there remains debate regarding the structure and development of
      executive functions. In an attempt to reconcile these discrepancies, a
      differentiation model of executive function development was evaluated in the
      early years using 6-month age groupings. Specifically, 281 preschoolers completed
      measures of working memory, inhibition, and shifting. Results contradicted
      suggestions that executive functions follow a single trajectory of progressive
      separation in childhood, instead suggesting that these functions may undergo a
      period of integration in the preschool years. These results highlight potential
      problems with current practices and theorizing in executive function research. 

PMID- 25852604
TI  - Musical plus phonological input for young foreign language readers.
AB  - Based on previous studies showing that phonological awareness is related to
      reading abilities and that music training improves phonological processing, the
      aim of the present study was to test for the efficiency of a new method for
      teaching to read in a foreign language. Specifically, we tested the efficacy of a
      phonological training program, with and without musical support that aimed at
      improving early reading skills in 7-8-year-old Spanish children (n = 63) learning
      English as a foreign language. Of interest was also to explore the impact of this
      training program on working memory and decoding skills. To achieve these goals we
      tested three groups of children before and after training: a control group, an
      experimental group with phonological non-musical intervention (active control),
      and an experimental group with musical intervention. Results clearly point to the
      beneficial effects of the phonological teaching approach but the further impact
      of the music support was not demonstrated. Moreover, while children in the music
      group showed low musical aptitudes before training, they nevertheless performed
      better than the control group. Therefore, the phonological training program with
      and without music support seem to have significant effects on early reading
      skills. 

PMID- 25852605
TI  - Are the deficits in navigational abilities present in the Williams syndrome
      related to deficits in the backward inhibition?
AB  - Williams syndrome (WS) is associated with a distinct profile of relatively
      proficient skills within the verbal domain compared to the severe impairment of
      visuo-spatial processing. Abnormalities in executive functions and deficits in
      planning ability and spatial working memory have been described. However, to date
      little is known about the influence of executive function deficits on
      navigational abilities in WS. This study aimed at analyzing in WS individuals a
      specific executive function, the backward inhibition (BI) that allows individuals
      to flexibly adapt to continuously changing environments. A group of WS
      individuals and a mental age- and gender-matched group of typically developing
      children were subjected to three task-switching experiments requiring
      visuospatial or verbal material to be processed. Results showed that WS
      individuals exhibited clear BI deficits during visuospatial task-switching
      paradigms and normal BI effect during verbal task-switching paradigm. Overall,
      the present results suggest that the BI involvement in updating environment
      representations during navigation may influence WS navigational abilities. 

PMID- 25852606
TI  - Impact on children of a parent with ALS: a case-control study.
AB  - BACKGROUND: Numerous studies have explored how patients and their caregivers cope
      with amyotrophic lateral sclerosis (ALS), but the literature completely lacks
      research on the psychological impact of the disease on patients' children. The
      aim of our study was to investigate the emotional and psychological impact of a
      parent with ALS on school-age children and adolescents in terms of problem
      behavior, adjustment, and personality characteristics. METHODS: The study
      involved 23 children (mean age = 10.62 years, six females) with a parent
      suffering from ALS, and both their parents. Children were matched for age,
      gender, and birth-order with a control group of children with healthy parents.
      They were administered the Youth Self Report (YSR) questionnaire and the
      Rorschach Comprehensive System, and their healthy parent completed the Child
      Behavior Checklist (CBCL). RESULTS: Findings clearly showed that, compared with
      controls, children with a parent who had ALS had several clinically significant
      adverse emotional and behavioral consequences, with emotional and behavioral
      problems, internalizing problems, anxiety and depressive symptoms. Children of a
      parent with ALS scored higher than controls for the Total Problems, Internalizing
      Problems, Anxious/Depressed and Withdrawn/Depressed scales in the YSR. A relevant
      percentage of children fell within the clinical range (42.9%) and borderline
      range (28.6%) for Internalizing Problems. The Rorschach CS confirmed the
      substantial impact of ALS in a parent on their offspring in terms of
      internalizing behavior and depression, with adjustment difficulties,
      psychological pain, and thought problems. CONCLUSION: Our findings indicate that
      school-aged children and adolescents with a parent who has ALS are vulnerable and
      carry a substantially higher risk of internalizing behavior, depressive symptoms,
      and reactive problems than children with healthy parents. Families affected may
      need support to cope with such an overwhelming disease.

PMID- 25852607
TI  - Clinical TVA-based studies: a general review.
AB  - In combination with whole report and partial report tasks, the theory of visual
      attention (TVA) can be used to estimate individual differences in five basic
      attentional parameters: the visual processing speed, the storage capacity of
      visual short-term memory, the perceptual threshold, the efficiency of top-down
      selectivity, and the spatial bias of attentional weighting. TVA-based assessment
      has been used in about 30 studies to investigate attentional deficits in a range
      of neurological and psychiatric conditions: (a) neglect and simultanagnosia, (b)
      reading disturbances, (c) aging and neurodegenerative diseases, and most recently
      (d) neurodevelopmental disorders. The article introduces TVA based assessment,
      discusses its methodology and psychometric properties, and reviews the progress
      made in each of the four research fields. The empirical results demonstrate the
      general usefulness of TVA-based assessment for many types of clinical
      neuropsychological research. The method's most important qualities are cognitive
      specificity and theoretical grounding, but it is also characterized by good
      reliability and sensitivity to minor deficits. The review concludes by pointing
      to promising new areas for clinical TVA-based research. 

PMID- 25852608
TI  - Facial feedback affects valence judgments of dynamic and static emotional
      expressions.
AB  - The ability to judge others' emotions is required for the establishment and
      maintenance of smooth interactions in a community. Several lines of evidence
      suggest that the attribution of meaning to a face is influenced by the facial
      actions produced by an observer during the observation of a face. However,
      empirical studies testing causal relationships between observers' facial actions
      and emotion judgments have reported mixed findings. This issue was investigated
      by measuring emotion judgments in terms of valence and arousal dimensions while
      comparing dynamic vs. static presentations of facial expressions. We presented
      pictures and videos of facial expressions of anger and happiness. Participants (N
      = 36) were asked to differentiate between the gender of faces by activating the
      corrugator supercilii muscle (brow lowering) and zygomaticus major muscle (cheek
      raising). They were also asked to evaluate the internal states of the stimuli
      using the affect grid while maintaining the facial action until they finished
      responding. The cheek raising condition increased the attributed valence scores
      compared with the brow-lowering condition. This effect of facial actions was
      observed for static as well as for dynamic facial expressions. These data suggest
      that facial feedback mechanisms contribute to the judgment of the valence of
      emotional facial expressions. 

PMID- 25852609
TI  - Starting off on the right foot: strong right-footers respond faster with the
      right foot to positive words and with the left foot to negative words.
AB  - Recent studies have provided evidence for an association between valence and
      left/right modulated by handedness, which is predicted by the body-specificity
      hypothesis (Casasanto, 2009) and also reflected in response times. We
      investigated whether such a response facilitation can also be observed with foot
      responses. Right-footed participants classified positive and negative words
      according to their valence by pressing a key with their left or right foot. A
      significant interaction between valence and foot only emerged in the by-items
      analysis. However, when dividing participants into two groups depending on the
      strength of their footedness, an interaction between valence and left/right was
      observed for strong right-footers, who responded faster with the right foot to
      positive words, and with the left foot to negative words. No interaction emerged
      for weak right-footers. The results strongly support the assumption that fluency
      lies at the core of the association between valence and left/right. 

PMID- 25852610
TI  - Limitless capacity: a dynamic object-oriented approach to short-term memory.
AB  - The notion of capacity-limited processing systems is a core element of cognitive
      accounts of limited and variable performance, enshrined within the short-term
      memory construct. We begin with a detailed critical analysis of the conceptual
      bases of this view and argue that there are fundamental problems - ones that go
      to the heart of cognitivism more generally - that render it untenable. In place
      of limited capacity systems, we propose a framework for explaining performance
      that focuses on the dynamic interplay of three aspects of any given setting: the
      particular task that must be accomplished, the nature and form of the material
      upon which the task must be performed, and the repertoire of skills and
      perceptual-motor functions possessed by the participant. We provide empirical
      examples of the applications of this framework in areas of performance typically
      accounted for by reference to capacity-limited short-term memory processes. 

PMID- 25852611
TI  - The intelligibility of r or r (2) as an effect size statistic: dichotomous
      variables.

PMID- 25852612
TI  - Methodological aspects to be considered when measuring the approximate number
      system (ANS) - a research review.
AB  - According to a dominant view, the approximate number system (ANS) is the
      foundation of symbolic math abilities. Due to the importance of math abilities
      for education and career, a lot of research focuses on the investigation of the
      ANS and its relationship with math performance. However, the results are
      inconsistent. This might be caused by studies differing greatly regarding the
      operationalization of the ANS (i.e., tasks, dependent variables). Moreover, many
      methodological aspects vary from one study to the next. In the present review, we
      discuss commonly used ANS tasks and dependent variables regarding their
      theoretical foundation and psychometric features. We argue that the inconsistent
      findings concerning the relationship between ANS acuity and math performance may
      be partially explained by differences in reliability. Furthermore, this review
      summarizes methodological aspects of ANS tasks having important impacts on the
      results, including stimulus range, visual controls, presentation duration of the
      stimuli and feedback. Based on this review, we give methodological
      recommendations on how to assess the ANS most reliably and most validly. All
      important methodological aspects to be considered when designing an ANS task or
      comparing results of different studies are summarized in two practical
      checklists. 

PMID- 25852613
TI  - Attachment style predicts affect, cognitive appraisals, and social functioning in
      daily life.
AB  - The way in which attachment styles are expressed in the moment as individuals
      navigate their real-life settings has remained an area largely untapped by
      attachment research. The present study examined how adult attachment styles are
      expressed in daily life using experience sampling methodology (ESM) in a sample
      of 206 Spanish young adults. Participants were administered the Attachment Style
      Interview (ASI) and received personal digital assistants that signaled them
      randomly eight times per day for 1 week to complete questionnaires about their
      current experiences and social context. As hypothesized, participants' momentary
      affective states, cognitive appraisals, and social functioning varied in
      meaningful ways as a function of their attachment style. Individuals with an
      anxious attachment, as compared with securely attached individuals, endorsed
      experiences that were congruent with hyperactivating tendencies, such as higher
      negative affect, stress, and perceived social rejection. By contrast, individuals
      with an avoidant attachment, relative to individuals with a secure attachment,
      endorsed experiences that were consistent with deactivating tendencies, such as
      decreased positive states and a decreased desire to be with others when alone.
      Furthermore, the expression of attachment styles in social contexts was shown to
      be dependent upon the subjective appraisal of the closeness of social contacts,
      and not merely upon the presence of social interactions. The findings support the
      ecological validity of the ASI and the person-by-situation character of
      attachment theory. Moreover, they highlight the utility of ESM for investigating
      how the predictions derived from attachment theory play out in the natural flow
      of real life. 

PMID- 25852614
TI  - Enhancing behavioral change with motivational interviewing: a case study in a
      Cardiac Rehabilitation Unit.
AB  - BACKGROUND: Psychological interventions in cardiac rehabilitation programs appear
      relevant in as much they significantly contribute to achieve the goals of
      rehabilitation, to reduce the risk of relapses and to improve patients' adherence
      to therapy. To this aim, motivational interviewing (MI) has shown promising
      results in improving motivation to change and individuals' confidence in their
      ability to do so. OBJECTIVE: The purpose of this article is to integrate theory
      with practice by describing a three-session case scenario. It illustrates how
      MI's skills and strategies can be used to enhance heart-healthy habits. MI may be
      synergistic with other treatment approaches and it is used here in conjunction
      with brief strategic therapy. CONCLUSION: By the use of MI principles and
      techniques, the patient reported an increase in his motivation and ability to
      change, developing a post discharge plan that incorporates self-care behaviors.
      CLINICAL IMPLICATIONS: MI may be effective in motivating and facilitating health
      behavior change among obese patients suffering from heart failure.

PMID- 25852615
TI  - Absolute and proportional measures of potential markers of rehearsal, and their
      implications for accounts of its development.
AB  - Previous studies of the development of phonological similarity and word length
      effects in children have shown that these effects are small or absent in young
      children, particularly when measured using visual presentation of the memoranda.
      This has often been taken as support for the view that young children do not
      rehearse. The current paper builds on recent evidence that instead suggests that
      absent phonological similarity and word length effects in young children reflects
      the same proportional cost of these effects in children of all ages. Our aims are
      to explore the conditions under which this proportional scaling account can
      reproduce existing developmental data, and in turn suggest ways that future
      studies might measure and model phonological similarity and word length effects
      in children. To that end, we first fit a single mathematical function through
      previously reported data that simultaneously captures absent and negative
      proportional effects of phonological similarity in young children plus constant
      proportional similarity effects in older children. This developmental function
      therefore provides the benchmark that we seek to re-produce in a series of
      subsequent simulations that test the proportional scaling account. These
      simulations reproduce the developmental function well, provided that they take
      into account the influence of floor effects and of measurement error. Our
      simulations suggest that future empirical studies examining these effects in the
      context of the development of rehearsal need to take into account proportional
      scaling. They also provide a demonstration of how proportional costs can be
      explored, and of the possible developmental functions associated with such an
      analysis. 

PMID- 25852616
TI  - Many faces of bankers' identity: how (not) to study dishonesty.

PMID- 25852617
TI  - The (un)suitability of modern liquid crystal displays (LCDs) for vision research.
AB  - Psychophysical and physiological studies of vision have traditionally used
      cathode ray tube (CRT) monitors to present stimuli. These monitors are no longer
      easily available, and liquid crystal display (LCD) technology is continually
      improving; therefore, we characterized a number of LCD monitors to determine if
      newer models are suitable replacements for CRTs in the laboratory. We compared
      the spatial and temporal characteristics of a CRT with five LCDs, including
      monitors designed with vision science in mind (ViewPixx and Display++),
      "prosumer" gaming monitors, and a consumer-grade LCD. All monitors had sufficient
      contrast, luminance range and reliability to support basic vision experiments
      with static images. However, the luminance of all LCDs depended strongly on
      viewing angle, which in combination with the poor spatial uniformity of all
      monitors except the VPixx, caused up to 80% drops in effective luminance in the
      periphery during central fixation. Further, all monitors showed significant
      spatial dependence, as the luminance of one area was modulated by the luminance
      of other areas. These spatial imperfections are most pronounced for experiments
      that use large or peripheral visual stimuli. In the temporal domain, the gaming
      LCDs were unable to generate reliable luminance patterns; one was unable to reach
      the requested luminance within a single frame whereas in the other the luminance
      of one frame affected the luminance of the next frame. The VPixx and Display++
      were less affected by these problems, and had good temporal properties provided
      stimuli were presented for 2 or more frames. Of the consumer-grade and gaming
      displays tested, and if problems with spatial uniformity are taken into account,
      the Eizo FG2421 is the most suitable alternative to CRTs. The specialized
      ViewPixx performed best among all the tested LCDs, followed closely by the
      Display++; both are good replacements for a CRT, provided their spatial
      imperfections are considered. 

PMID- 25852618
TI  - The self in conflict: actors and agency in the mediated sequential Simon task.
AB  - Executive control refers to the ability to withstand interference in order to
      achieve task goals. The effect of conflict adaptation describes that after
      experiencing interference, subsequent conflict effects are weaker. However,
      changes in the source of conflict have been found to disrupt conflict adaptation.
      Previous studies indicated that this specificity is determined by the degree to
      which one source causes episodic retrieval of a previous source. A virtual
      reality version of the Simon task was employed to investigate whether changes in
      a visual representation of the self would similarly affect conflict adaptation.
      Participants engaged in a mediated Simon task via 3D "avatar" models that either
      mirrored the participants' movements, or were presented statically. A retrieval
      cue was implemented as the identity of the avatar: switching it from a male to a
      female avatar was expected to disrupt the conflict adaptation effect (CAE). The
      results show that only in static conditions did the CAE depend on the avatar
      identity, while in dynamic conditions, changes did not cause disruption. We also
      explored the effect of conflict and adaptation on the degree of movement made
      with the task-irrelevant hand and replicated the reaction time pattern. The
      findings add to earlier studies of source-specific conflict adaptation by showing
      that a visual representation of the self in action can provide a cue that
      determines episodic retrieval. Furthermore, the novel paradigm is made openly
      available to the scientific community and is described in its significance for
      studies of social cognition, cognitive psychology, and human-computer
      interaction. 

PMID- 25852619
TI  - Commentary on: "The body social: an enactive approach to the self". A tool for
      merging bodily and social self in immobile individuals.

PMID- 25852620
TI  - What you see is what you get: webcam placement influences perception and social
      coordination.
AB  - Building on a well-established link between elevation and social power, we
      demonstrate that-when perceptual information is limited-subtle visual cues can
      shape people's representations of others and, in turn, alter strategic social
      behavior. A cue to elevation (unrelated to physical size) provided by the
      placement of web cameras in a video chat biased individuals' perceptions of a
      partner's height (Experiment 1) and shaped the extent to which they made
      decisions in their own self-interest: participants tended to coordinate their
      behavior in a manner that benefitted the preferences of a partner pictured from a
      low camera angle during a game of asymmetric coordination (Experiment 2). Our
      results suggest that people are vulnerable to the influence of a limited
      viewpoint when forming representations of others in a manner that shapes their
      strategic choices. 

PMID- 25852621
TI  - Problematic assumptions have slowed down depression research: why symptoms, not
      syndromes are the way forward.
AB  - Major depression (MD) is a highly heterogeneous diagnostic category. Diverse
      symptoms such as sad mood, anhedonia, and fatigue are routinely added to an
      unweighted sum-score, and cutoffs are used to distinguish between depressed
      participants and healthy controls. Researchers then investigate outcome variables
      like MD risk factors, biomarkers, and treatment response in such samples. These
      practices presuppose that (1) depression is a discrete condition, and that (2)
      symptoms are interchangeable indicators of this latent disorder. Here I review
      these two assumptions, elucidate their historical roots, show how deeply
      engrained they are in psychological and psychiatric research, and document that
      they contrast with evidence. Depression is not a consistent syndrome with clearly
      demarcated boundaries, and depression symptoms are not interchangeable indicators
      of an underlying disorder. Current research practices lump individuals with very
      different problems into one category, which has contributed to the remarkably
      slow progress in key research domains such as the development of efficacious
      antidepressants or the identification of biomarkers for depression. The recently
      proposed network framework offers an alternative to the problematic assumptions.
      MD is not understood as a distinct condition, but as heterogeneous symptom
      cluster that substantially overlaps with other syndromes such as anxiety
      disorders. MD is not framed as an underlying disease with a number of equivalent
      indicators, but as a network of symptoms that have direct causal influence on
      each other: insomnia can cause fatigue which then triggers concentration and
      psychomotor problems. This approach offers new opportunities for constructing an
      empirically based classification system and has broad implications for future
      research. 

PMID- 25852622
TI  - Shifting goals: effects of active and observational experience on infants'
      understanding of higher order goals.
AB  - Action perception links have been argued to support the emergence of action
      understanding, but their role in infants' perception of distal goals has not been
      fully investigated. The current experiments address this issue. During the
      development of means-end actions, infants shift their focus from the means of the
      action to the distal goal. In Experiment One, we evaluated whether this same
      shift in attention (from the means to the distal goal) when learning to produce
      multi-step actions is reflected in infants' perception of others' means-end
      actions. Eight-months-old infants underwent active training in means-end action
      production and their subsequent analysis of an observed means-end action was
      assessed in a visual habituation paradigm. Infants' degree of success in the
      training paradigm was related to their subsequent interpretation of the observed
      action as directed at the means versus the distal goal. In Experiment Two,
      observational and control manipulations provided evidence that these effects
      depended on the infants' active engagement in the means-end actions. These
      results suggest that the processes that give rise to means-end structure in
      infants' motor behavior also support the emergence of means-end structure in
      their analysis of others' goals. 

PMID- 25852623
TI  - Working memory differences in long-distance dependency resolution.
AB  - There is a wealth of evidence showing that increasing the distance between an
      argument and its head leads to more processing effort, namely, locality effects;
      these are usually associated with constraints in working memory (DLT: Gibson,
      2000; activation-based model: Lewis and Vasishth, 2005). In SOV languages,
      however, the opposite effect has been found: antilocality (see discussion in Levy
      et al., 2013). Antilocality effects can be explained by the expectation-based
      approach as proposed by Levy (2008) or by the activation-based model of sentence
      processing as proposed by Lewis and Vasishth (2005). We report an eye-tracking
      and a self-paced reading study with sentences in Spanish together with measures
      of individual differences to examine the distinction between expectation- and
      memory-based accounts, and within memory-based accounts the further distinction
      between DLT and the activation-based model. The experiments show that (i)
      antilocality effects as predicted by the expectation account appear only for high
      capacity readers; (ii) increasing dependency length by interposing material that
      modifies the head of the dependency (the verb) produces stronger facilitation
      than increasing dependency length with material that does not modify the head;
      this is in agreement with the activation-based model but not with the expectation
      account; and (iii) a possible outcome of memory load on low-capacity readers is
      the increase in regressive saccades (locality effects as predicted by memory
      based accounts) or, surprisingly, a speedup in the self-paced reading task; the
      latter consistent with good-enough parsing (Ferreira et al., 2002). In sum, the
      study suggests that individual differences in working memory capacity play a role
      in dependency resolution, and that some of the aspects of dependency resolution
      can be best explained with the activation-based model together with a prediction
      component. 

PMID- 25852624
TI  - The relational responding task: toward a new implicit measure of beliefs.
AB  - We introduce the Relational Responding Task (RRT) as a tool for capturing beliefs
      at the implicit level. Flemish participants were asked to respond as if they
      believed that Flemish people are more intelligent than immigrants (e.g., respond
      "true" to the statement "Flemish people are wiser than immigrants") or to respond
      as if they believed that immigrants are more intelligent than Flemish people
      (e.g., respond "true" to the statement "Flemish people are dumber than
      immigrants"). The difference in performance between these two tasks correlated
      with ratings of the extent to which participants explicitly endorsed the belief
      that Flemish people are more intelligent than immigrants and with questionnaire
      measures of subtle and blatant racism. The current study provides a first step
      toward validating RRT effects as a viable measure of implicit beliefs. 

PMID- 25852625
TI  - Grounding context in face processing: color, emotion, and gender.
AB  - In recent years, researchers have become interested in the way that the affective
      quality of contextual information transfers to a perceived target. We therefore
      examined the effect of a red (vs. green, mixed red/green, and achromatic)
      background - known to be valenced - on the processing of stimuli that play a key
      role in human interactions, namely facial expressions. We also examined whether
      the valenced-color effect can be modulated by gender, which is also known to be
      valenced. Female and male adult participants performed a categorization task of
      facial expressions of emotion in which the faces of female and male posers
      expressing two ambiguous emotions (i.e., neutral and surprise) were presented
      against the four different colored backgrounds. Additionally, this task was
      completed by collecting subjective ratings for each colored background in the
      form of five semantic differential scales corresponding to both discrete and
      dimensional perspectives of emotion. We found that the red background resulted in
      more negative face perception than the green background, whether the poser was
      female or male. However, whereas this valenced-color effect was the only effect
      for female posers, for male posers, the effect was modulated by both the nature
      of the ambiguous emotion and the decoder's gender. Overall, our findings offer
      evidence that color and gender have a common valence-based dimension. 

PMID- 25852627
TI  - Commentary on: "Agency, time, and causality".

PMID- 25852626
TI  - Semantic memory as the root of imagination.

PMID- 25852628
TI  - Prospect theory and body mass: characterizing psychological parameters for weight
      related risk attitudes and weight-gain aversion.
AB  - We developed a novel decision-making paradigm that allows us to apply prospect
      theory in behavioral economics to body mass. 67 healthy young adults completed
      self-report measures and two decision-making tasks for weight-loss, as well as
      for monetary rewards. We estimated risk-related preference and loss aversion
      parameters for each individual, separately for weight-loss and monetary rewards
      choice data. Risk-seeking tendency for weight-loss was positively correlated with
      body mass index in individuals who desired to lose body weight, whereas the risk
      seeking for momentary rewards was not. Risk-seeking for weight-loss was
      correlated to excessive body shape preoccupations, while aversion to weight-gain
      was correlated with self-reports of behavioral involvement for successful weight
      loss. We demonstrated that prospect theory can be useful in explaining the
      decision-making process related to body mass. Applying prospect theory is
      expected to advance our understanding of decision-making mechanisms in obesity,
      which might prove helpful for improving healthy choices. 

PMID- 25852629
TI  - The processing of raising and nominal control: an eye-tracking study.
AB  - According to some views of sentence processing, the memory retrieval processes
      involved in dependency formation may differ as a function of the type of
      dependency involved. For example, using closely matched materials in a single
      experiment, Dillon et al. (2013) found evidence for retrieval interference in
      subject-verb agreement, but not in reflexive-antecedent agreement. We report four
      eye-tracking experiments that examine examine reflexive-antecedent dependencies,
      combined with raising (e.g., "John seemed to Tom to be kind to himself..."), or
      nominal control (e.g., "John's agreement with Tom to be kind to himself..."). We
      hypothesized that dependencies involving raising would (a) be processed more
      quickly, and (b) be less subject to retrieval interference, relative to those
      involving nominal control. This is due to the fact that the interpretation of
      raising is structurally constrained, while the interpretation of nominal control
      depends crucially on lexical properties of the control nominal. The results
      showed evidence of interference when the reflexive-antecedent dependency was
      mediated by raising or nominal control, but very little evidence that could be
      interpreted in terms of interference for direct reflexive-antecedent dependencies
      that did not involve raising or control. However, there was no evidence either
      for greater interference, or for quicker dependency formation, for raising than
      for nominal control. 

PMID- 25852630
TI  - Testing normative and self-appraisal feedback in an online slot-machine pop-up in
      a real-world setting.
AB  - Over the last few years, there have been an increasing number of gaming operators
      that have incorporated on-screen pop-up messages while gamblers play on slot
      machines and/or online as one of a range of tools to help encourage responsible
      gambling. Coupled with this, there has also been an increase in empirical
      research into whether such pop-up messages are effective, particularly in
      laboratory settings. However, very few studies have been conducted on the utility
      of pop-up messages in real-world gambling settings. The present study
      investigated the effects of normative and self-appraisal feedback in a slot
      machine pop-up message compared to a simple (non-enhanced) pop-up message. The
      study was conducted in a real-world gambling environment by comparing the
      behavioral tracking data of two representative random samples of 800,000 gambling
      sessions (i.e., 1.6 million sessions in total) across two conditions (i.e.,
      simple pop-up message versus an enhanced pop-up message). The results indicated
      that the additional normative and self-appraisal content doubled the number of
      gamblers who stopped playing after they received the enhanced pop-up message
      (1.39%) compared to the simple pop-up message (0.67%). The data suggest that pop
      up messages influence only a small number of gamblers to cease long playing
      sessions and that enhanced messages are slightly more effective in helping
      gamblers to stop playing in-session. 

PMID- 25852631
TI  - Bench-to-Bedside and Bedside Back to the Bench; Seeking a Better Understanding of
      the Acute Pathophysiological Process in Severe Traumatic Brain Injury.
AB  - Despite substantial investments, traumatic brain injury (TBI) remains one of the
      major disorders that lack specific pharmacotherapy. To a substantial degree, this
      situation is due to lack of understanding of the pathophysiological process of
      the disease. Experimental TBI research offers controlled, rapid, and cost
      effective means to identify the pathophysiology but translating experimental
      findings into clinical practice can be further improved by using the same or
      similar outcome measures and clinically relevant time points. The pathophysiology
      during the acute phase of severe TBI is especially poorly understood. In this
      Mini review, I discuss some of the incongruences between current clinical
      practices and needs versus information provided by experimental TBI research as
      well as the benefits of designing animal experiments with translation into
      clinical practice in mind. 

PMID- 25852633
TI  - Ubiquitin carboxy-terminal hydrolase-l1 as a serum neurotrauma biomarker for
      exposure to occupational low-level blast.
AB  - Repeated exposure to low-level blast is a characteristic of a few select
      occupations and there is concern that such occupational exposures present risk
      for traumatic brain injury. These occupations include specialized military and
      law enforcement units that employ controlled detonation of explosive charges for
      the purpose of tactical entry into secured structures. The concern for negative
      effects from blast exposure is based on rates of operator self-reported headache,
      sleep disturbance, working memory impairment, and other concussion-like symptoms.
      A challenge in research on this topic has been the need for improved assessment
      tools to empirically evaluate the risk associated with repeated exposure to blast
      overpressure levels commonly considered to be too low in magnitude to cause acute
      injury. Evaluation of serum-based neurotrauma biomarkers provides an objective
      measure that is logistically feasible for use in field training environments.
      Among candidate biomarkers, ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1) has
      some empirical support and was evaluated in this study. We used daily blood draws
      to examine acute change in UCH-L1 among 108 healthy military personnel who were
      exposed to repeated low-level blast across a 2-week period. These research
      volunteers also wore pressure sensors to record blast exposures, wrist actigraphs
      to monitor sleep patterns, and completed daily behavioral assessments of
      symptomology, postural stability, and neurocognitive function. UCH-L1 levels were
      elevated as a function of participating in the 2-week training with explosives,
      but the correlation of UCH-L1 elevation and blast magnitude was weak and
      inconsistent. Also, UCH-L1 elevations did not correlate with deficits in
      behavioral measures. These results provide some support for including UCH-L1 as a
      measure of central nervous system effects from exposure to low-level blast.
      However, the weak relation observed suggests that additional indicators of blast
      effect are needed. 

PMID- 25852634
TI  - The Role of fMRI to Assess Plasticity of the Motor System in MS.

PMID- 25852632
TI  - Vascular and inflammatory factors in the pathophysiology of blast-induced brain
      injury.
AB  - Blast-related traumatic brain injury (TBI) has received much recent attention
      because of its frequency in the conflicts in Iraq and Afghanistan. This renewed
      interest has led to a rapid expansion of clinical and animal studies related to
      blast. In humans, high-level blast exposure is associated with a prominent
      hemorrhagic component. In animal models, blast exerts a variety of effects on the
      nervous system including vascular and inflammatory effects that can be seen with
      even low-level blast exposures which produce minimal or no neuronal pathology.
      Acutely, blast exposure in animals causes prominent vasospasm and decreased
      cerebral blood flow along with blood-brain barrier breakdown and increased
      vascular permeability. Besides direct effects on the central nervous system,
      evidence supports a role for a thoracically mediated effect of blast; whereby,
      pressure waves transmitted through the systemic circulation damage the brain.
      Chronically, a vascular pathology has been observed that is associated with
      alterations of the vascular extracellular matrix. Sustained microglial and
      astroglial reactions occur after blast exposure. Markers of a central and
      peripheral inflammatory response are found for sustained periods after blast
      injury and include elevation of inflammatory cytokines and other inflammatory
      mediators. At low levels of blast exposure, a microvascular pathology has been
      observed in the presence of an otherwise normal brain parenchyma, suggesting that
      the vasculature may be selectively vulnerable to blast injury. Chronic immune
      activation in brain following vascular injury may lead to neurobehavioral changes
      in the absence of direct neuronal pathology. Strategies aimed at preventing or
      reversing vascular damage or modulating the immune response may improve the
      chronic neuropsychiatric symptoms associated with blast-related TBI. 

PMID- 25852635
TI  - Measuring Gray Matter and White Matter Damage in MS: Why This is Not Enough.

PMID- 25852636
TI  - Left atrial septal pouch in cryptogenic stroke.
AB  - BACKGROUND: The left atrial septal pouch (LASP), an anatomic variant of the
      interatrial septum, has uncertain clinical significance. We examined the
      association between LASP and ischemic stroke subtypes in patients undergoing
      transesophageal echocardiography (TEE). METHODS: We determined the prevalence of
      LASP among consecutive patients who underwent TEE at our institution. Patients
      identified with ischemic strokes were further evaluated for stroke subtype using
      standard and modified criteria from the Trial of Org 10172 in Acute Stroke
      Treatment (TOAST). We compared the prevalence of LASP in ischemic stroke,
      cryptogenic stroke, and non-stroke patients using prevalence ratios (PR).
      RESULTS: The mean age of all 212 patients (including stroke and non-stroke
      patients) was 57 years. The overall prevalence of LASP was 17% (n = 35). Of the
      75 patients who were worked-up for stroke at our institution during study period,
      we classified 31 as cryptogenic using standard TOAST criteria. The prevalence of
      LASP among cryptogenic stroke patients (using standard and modified TOAST
      criteria) was increased compared to the prevalence among other ischemic stroke
      patients (26 vs. 9%, p = 0.06; PR = 1.8, 95% CI = 1.1-3.1, and 30 vs. 10%, p =
      0.04; PR = 2.2, 95% CI = 1.2-4.1, respectively). CONCLUSION: In this population
      of relatively young patients, prevalence of LASP was increased in cryptogenic
      stroke compared to stroke patients of other subtypes. These findings suggest LASP
      is associated with cryptogenic stroke, which should be verified by future large
      scale studies.

PMID- 25852637
TI  - Horizontal Eye Position Affects Measured Vertical VOR Gain on the Video Head
      Impulse Test.
AB  - BACKGROUND/HYPOTHESIS: With the video head impulse test (vHIT), the vertical VOR
      gain is defined as (vertical eye velocity/vertical head velocity), but
      compensatory eye movements to vertical canal stimulation usually have a torsional
      component. To minimize the contribution of torsion to the eye movement
      measurement, the horizontal gaze direction should be directed 40 degrees  from
      straight ahead so it is in the plane of the stimulated canal plane pair.
      HYPOTHESIS: as gaze is systematically moved horizontally away from canal plane
      alignment, the measured vertical VOR gain should decrease. STUDY DESIGN: Ten
      healthy subjects, with vHIT measuring vertical eye movement to head impulses in
      the plane of the left anterior-right posterior (LARP) canal plane, with gaze at
      one of five horizontal gaze positions [40 degrees (aligned with the LARP plane),
      20 degrees , 0 degrees , -20 degrees , -40 degrees ]. METHODS: Every head impulse
      was in the LARP plane. The compensatory eye movement was measured by the vHIT
      prototype system. The one operator delivered every impulse. RESULTS: The canal
      stimulus remained identical across trials, but the measured vertical VOR gain
      decreased as horizontal gaze angle was shifted away from alignment with the LARP
      canal plane. CONCLUSION: In measuring vertical VOR gain with vHIT the horizontal
      gaze angle should be aligned with the canal plane under test.

PMID- 25852638
TI  - Neuroplasticity and motor rehabilitation in multiple sclerosis.

PMID- 25852639
TI  - Cannabinoid CB1 Receptor Agonists Do Not Decrease, but may Increase Acoustic
      Trauma-Induced Tinnitus in Rats.
AB  - Tinnitus has been suggested to arise from neuronal hyperactivity in auditory
      areas of the brain, and anti-epileptic drugs are sometimes used to provide relief
      from tinnitus. Recently, the anti-epileptic properties of the cannabinoid drugs
      have gained increasing interest; however, the use of cannabinoids as a form of
      treatment for tinnitus is controversial. In this study, we tested whether a
      combination of delta-9-tetrahydrocannabinol (delta-9-THC) and cannabidiol (CBD),
      delivered in a 1:1 ratio, could affect tinnitus perception in a rat model of
      acoustic trauma-induced tinnitus. Following sham treatment or acoustic trauma,
      the animals were divided into the following groups: (1) sham (i.e., no acoustic
      trauma) with vehicle treatment; (2) sham with drug treatment (i.e., delta-9-THC +
      CBD); (3) acoustic trauma-exposed exhibiting tinnitus, with drug treatment; and
      (4) acoustic trauma-exposed exhibiting no tinnitus, with drug treatment. The
      animals received either the vehicle or the cannabinoid drugs every day, 30 min
      before the tinnitus behavioral testing. Acoustic trauma caused a significant
      increase in the auditory brainstem response (ABR) thresholds in the exposed
      animals, indicating hearing loss; however, there was a partial recovery over 6
      months. Acoustic trauma did not always result in tinnitus; however, among those
      that did exhibit tinnitus, some of them had tinnitus at multiple frequencies
      while others had it only at a single frequency. The cannabinoids significantly
      increased the number of tinnitus animals in the exposed-tinnitus group, but not
      in the sham group. The results suggest that cannabinoids may promote the
      development of tinnitus, especially when there is pre-existing hearing damage. 

PMID- 25852640
TI  - Biochemical response to hyperbaric oxygen treatment of a transhemispheric
      penetrating cerebral gunshot injury.
AB  - Hyperbaric oxygen (HBO) therapy has been suggested a treatment option in order to
      reduce the development of secondary insults succeeding traumatic brain injury.
      This case report studied the course of a 23-year-old gentleman with a close range
      transhemispheric gunshot wound. The biochemical parameters, using a multi-modal
      monitoring in the neuro-intensive care unit, improved following HBO treatment. 

PMID- 25852641
TI  - Demyelinating and thrombotic diseases of the central nervous system: common
      pathogenic and triggering factors.

PMID- 25852642
TI  - Ethnic differences in bone health.
AB  - There are differences in bone health between ethnic groups in both men and in
      women. Variations in body size and composition are likely to contribute to
      reported differences. Most studies report ethnic differences in areal bone
      mineral density (aBMD), which do not consistently parallel ethnic patterns in
      fracture rates. This suggests that other parameters beside aBMD should be
      considered when determining fracture risk between and within populations,
      including other aspects of bone strength: bone structure and microarchitecture,
      as well as muscle strength (mass, force generation, anatomy) and fat mass. We
      review what is known about differences in bone-densitometry-derived outcomes
      between ethnic groups and the extent to which they account for the differences in
      fracture risk. Studies are included that were published primarily between 1994
      and 2014. A "one size fits all approach" should definitely not be used to
      understand better ethnic differences in fracture risk. 

PMID- 25852643
TI  - Diabetes, diet-health behavior, and obesity.
AB  - High-quality diets play an important role in diabetes prevention. Appropriate
      dietary adherence can improve insulin sensitivity and glycemic control, and thus
      contribute to lifestyle improvement. However, previous research suggests that
      dietary adherence is arguably among the most difficult cornerstones of diabetes
      management. The objectives of this study are (1) to estimate whether and to what
      extent individuals diagnosed with diabetes show significant differences in diet
      quality [healthy eating index (HEI)] compared to healthy individuals, (2) to
      quantify whether and to what extent diabetics experience significantly higher
      outcomes of body mass index (BMI), and (3) to estimate whether and to what extent
      dietary supplementation impacts diabetes patient's diet quality and/or BMI
      outcomes. We use data from the 2007-2008 U.S. National Health and Nutrition
      Examination Survey (NHANES). The NHANES is the primary, randomized, and
      nationally representative survey used to assess the health and nutritional status
      in the U.S. We apply propensity score matching (PSM) to account for selection
      bias and endogeneity between self-reported diet and health behavir (treatment)
      and BMI outcomes. We control for an individual's BMI as to capture the impact of
      past dietary behavior in its impact on HEI. Matching results suggest that regular
      dietary supplement consumption is associated with significant lower BMI outcomes
      of almost 1 kg/m(2). The close relationship between diabetes and obesity has been
      at the center of the diet-health policy debate across Canada and the U.S.
      Knowledge about this linkage may help to improve the understanding of the factors
      that impact dietary choices and their overall health outcomes, which may lead to
      a more efficient and effective promotion of dietary guidelines, healthy food
      choices, and targeted consumer health and lifestyle policies. 

PMID- 25852645
TI  - Ubiquitin-fold modifier 1 acts as a positive regulator of breast cancer.
AB  - Estrogen receptor-alpha (ERalpha) is a steroid hormone-sensitive transcription
      factor that plays a critical role in development of breast cancer. The binding of
      estrogen to ERalpha triggers the recruitment of transcriptional co-activators as
      well as chromatin remodeling factors to estrogen-responsive elements (ERE) of
      ERalpha target genes. This process is tightly associated with post-translational
      modifications (PTMs) of ERalpha and its co-activators for promotion of
      transcriptional activation, which leads to proliferation of a large subset of
      breast tumor cells. These PTMs include phosphorylation, acetylation, methylation,
      and conjugation by ubiquitin and ubiquitin-like proteins. Ubiquitin-fold modifier
      1 (UFM1), one of ubiquitin-like proteins, has recently been shown to be ligated
      to activating signal co-integrator 1 (ASC1), which acts as a transcriptional co
      activator of nuclear receptors. Here, we discuss the mechanistic connection
      between ASC1 modification by UFM1 and ERalpha transactivation, and highlight how
      the interplay of these processes is involved in development of breast cancer. We
      also discuss potential use of UFM1-conjugating system as therapeutic targets
      against not only breast cancer but also other nuclear receptor-mediated cancers. 

PMID- 25852646
TI  - Nuclear progestin receptor (pgr) knockouts in zebrafish demonstrate role for pgr
      in ovulation but not in rapid non-genomic steroid mediated meiosis resumption.
AB  - Progestins, progesterone derivatives, are the most critical signaling steroid for
      initiating final oocyte maturation (FOM) and ovulation, in order to advance fully
      grown immature oocytes to become fertilizable eggs in basal vertebrates. It is
      well-established that progestin induces FOM at least partly through a membrane
      receptor and a non-genomic steroid signaling process, which precedes progestin
      triggered ovulation that is mediated through a nuclear progestin receptor (Pgr)
      and genomic signaling pathway. To determine whether Pgr plays a role in a non
      genomic signaling mechanism during FOM, we knocked out Pgr in zebrafish using
      transcription activator-like effector nucleases (TALENs) and studied the oocyte
      maturation phenotypes of Pgr knockouts (Pgr-KOs). Three TALENs-induced mutant
      lines with different frame shift mutations were generated. Homozygous Pgr-KO
      female fish were all infertile while no fertility effects were evident in
      homozygous Pgr-KO males. Oocytes developed and underwent FOM normally in vivo in
      homozygous Pgr-KO female compared to the wild-type controls, but these mature
      oocytes were trapped within the follicular cells and failed to ovulate from the
      ovaries. These oocytes also underwent normal germinal vesicle breakdown (GVBD)
      and FOM in vitro, but failed to ovulate even after treatment with human chronic
      gonadotropin (HCG) or progestin (17alpha,20beta-dihydroxyprogesterone or DHP),
      which typically induce FOM and ovulation in wild-type oocytes. The results
      indicate that anovulation and infertility in homozygous Pgr-KO female fish was,
      at least in part, due to a lack of functional Pgr-mediated genomic progestin
      signaling in the follicular cells adjacent to the oocytes. Our study of Pgr-KO
      supports previous results that demonstrate a role for Pgr in steroid-dependent
      genomic signaling pathways leading to ovulation, and the first convincing
      evidence that Pgr is not essential for initiating non-genomic progestin signaling
      and triggering of meiosis resumption. 

PMID- 25852644
TI  - Manipulating the circadian and sleep cycles to protect against metabolic disease.
AB  - Modernization of human society parallels an epidemic of metabolic disorders
      including obesity. Apart from excess caloric intake, a 24/7 lifestyle poses
      another important challenge to our metabolic health. Recent research under both
      laboratory and epidemiological settings has indicated that abnormal temporal
      organization of sleep and wakeful activities including food intake is a
      significant risk factor for metabolic disease. The circadian clock system is our
      intrinsic biological timer that regulates internal rhythms such as the sleep/wake
      cycle and also responses to external stimuli including light and food. Initially
      thought to be mainly involved in the timing of sleep, the clock, and/or clock
      genes may also play a role in sleep architecture and homeostasis. Importantly, an
      extensive body of evidence has firmly established a master regulatory role of the
      clock in energy balance. Together, a close relationship between well-timed
      circadian/sleep cycles and metabolic health is emerging. Exploiting this
      functional connection, an important holistic strategy toward curbing the epidemic
      of metabolic disorders (e.g., obesity) involves corrective measures on the
      circadian clock and sleep. In addition to behavioral and environmental
      interventions including meal timing and light control, pharmacological agents
      targeting sleep and circadian clocks promise convenient and effective
      applications. Recent studies, for example, have reported small molecules
      targeting specific clock components and displaying robust beneficial effects on
      sleep and metabolism. Furthermore, a group of clock-amplitude-enhancing small
      molecules (CEMs) identified via high-throughput chemical screens are of
      particular interest for future in vivo studies of their metabolic and sleep
      efficacies. Elucidating the functional relationship between clock, sleep, and
      metabolism will also have far-reaching implications for various chronic human
      diseases and aging. 

PMID- 25852647
TI  - Micro CT Analysis of Spine Architecture in a Mouse Model of Scoliosis.
AB  - OBJECTIVE: Mice homozygous for targeted deletion of the gene encoding fibroblast
      growth factor receptor 3 (FGFR3(-/-)) develop kyphoscoliosis by 2 months of age.
      The first objective of this study was to use high resolution X-ray to
      characterize curve progression in vivo and micro CT to quantify spine
      architecture ex vivo in FGFR3(-/-) mice. The second objective was to determine if
      slow release of the bone anabolic peptide parathyroid hormone related protein
      (PTHrP-1-34) from a pellet placed adjacent to the thoracic spine could inhibit
      progressive kyphoscoliosis. MATERIALS AND METHODS: Pellets loaded with placebo or
      PTHrP-1-34 were implanted adjacent to the thoracic spine of 1-month-old FGFR3(-/
      ) mice obtained from in house breeding. X rays were captured at monthly intervals
      up to 4 months to quantify curve progression using the Cobb method. High
      resolution post-mortem scans of FGFR3(-/-) and FGFR3(+/+) spines, from C5/6 to
      L4/5, were captured to evaluate the 3D structure, rotation, and micro
      architecture of the affected vertebrae. Un-decalcified and decalcified histology
      were performed on the apical and adjacent vertebrae of FGFR3(-/-) spines, and the
      corresponding vertebrae from FGFR3(+/+) spines. RESULTS: The mean Cobb angle was
      significantly greater at all ages in FGFR3(-/-) mice compared with wild type mice
      and appeared to stabilize around skeletal maturity at 4 months. 3D
      reconstructions of the thoracic spine of 4-month-old FGFR3(-/-) mice treated with
      PTHrP-1-34 revealed correction of left/right asymmetry, vertebral rotation, and
      lateral displacement compared with mice treated with placebo. Histologic analysis
      of the apical vertebrae confirmed correction of the asymmetry in PTHrP-1-34
      treated mice, in the absence of any change in bone volume, and a significant
      reduction in the wedging of intervertebral disks (IVD) seen in placebo treated
      mice. CONCLUSION: Local treatment of the thoracic spine of juvenile FGFR3(-/-)
      mice with a bone anabolic agent inhibited progression of scoliosis, but with
      little impact on kyphosis. The significant improvement in IVD integrity suggests
      PTHrP-1-34 might also be considered as a therapeutic agent for degenerative disk
      disorders.

PMID- 25852648
TI  - The Hypoxia-Inducible Factor Pathway in Adipocytes: The Role of HIF-2 in Adipose
      Inflammation and Hypertrophic Cardiomyopathy.
AB  - Under obese conditions, adipose tissue can become oxygen-deficient or hypoxic.
      Extensive work has been done using various diet-induced obesity models to
      demonstrate an important role of hypoxia-induced signaling in adipose tissue and
      its impact on adipose functions related to adipogenesis, insulin sensitivity, and
      inflammation. We have recently identified a new mechanism connecting activation
      of the hypoxia-sensing pathway manifested by hypoxia-inducible factor (HIF)
      2alpha to adipose tissue inflammation and hypertrophic cardiomyopathy.
      Interestingly, this observation is consistent with the clinical evidence showing
      that obesity is often associated with ventricular hypertrophy and dysfunction as
      well as congestive heart failure independent of other well-established risk
      factors including diabetes, hypertension, and coronary artery disease. This brief
      review will discuss the currently published genetic mouse models to determine the
      role of the HIF pathway in adipose tissue-associated diseases with a focus on the
      newly identified role of adipocyte HIF-2 in the development of hypertrophic
      cardiomyopathy. 

PMID- 25852650
TI  - Transcriptome analyses to investigate symbiotic relationships between marine
      protists.
AB  - Rhizaria are an important component of oceanic plankton communities worldwide. A
      number of species harbor eukaryotic microalgal symbionts, which are horizontally
      acquired in the environment at each generation. Although these photosymbioses are
      determinant for Rhizaria ability to thrive in oceanic ecosystems, the mechanisms
      for symbiotic interactions are unclear. Using high-throughput sequencing
      technology (i.e., 454), we generated large Expressed Sequence Tag (EST) datasets
      from four uncultured Rhizaria, an acantharian (Amphilonche elongata), two
      polycystines (Collozoum sp. and Spongosphaera streptacantha), and one phaeodarian
      (Aulacantha scolymantha). We assessed the main genetic features of the
      host/symbionts consortium (i.e., the holobiont) transcriptomes and found rRNA
      sequences affiliated to a wide range of bacteria and protists in all samples,
      suggesting that diverse microbial communities are associated with the holobionts.
      A particular focus was then carried out to search for genes potentially involved
      in symbiotic processes such as the presence of c-type lectins-coding genes, which
      are proteins that play a role in cell recognition among eukaryotes. Unigenes
      coding putative c-type lectin domains (CTLD) were found in the species bearing
      photosynthetic symbionts (A. elongata, Collozoum sp., and S. streptacantha) but
      not in the non-symbiotic one (A. scolymantha). More particularly, phylogenetic
      analyses group CTLDs from A. elongata and Collozoum sp. on a distinct branch from
      S. streptacantha CTLDs, which contained carbohydrate-binding motifs typically
      observed in other marine photosymbiosis. Our data suggest that similarly to other
      well-known marine photosymbiosis involving metazoans, the interactions of glycans
      with c-type lectins is likely involved in modulation of the host/symbiont
      specific recognition in Radiolaria. 

PMID- 25852649
TI  - Coupling Signals between the Osteoclast and Osteoblast: How are Messages
      Transmitted between These Temporary Visitors to the Bone Surface?

PMID- 25852651
TI  - Endocytotic uptake of FITC-labeled anti-H. pylori egg yolk immunoglobulin Y in
      Candida yeast for detection of intracellular H. pylori.
AB  - Intracellular life of Helicobacter pylori inside Candida yeast vacuole describes
      the establishment of H. pylori in yeast as a pre-adaptation to life in human
      epithelial cells. IgY-Hp conjugated with fluorescein isothiocyanate (FITC) has
      been previously used for identification and localization of H. pylori inside the
      yeast vacuole. Here we examined whether FITC-IgY-Hp internalization into yeast
      follows the endocytosis pathway in yeast. Fluorescent microscopy was used to
      examine the entry of FITC-IgY-Hp into Candida yeast cells at different time
      intervals. The effect of low temperature, H2O2 or acetic acid on the
      internalization of labeled antibody was also examined. FITC-IgY-Hp
      internalization initiated within 0-5 min in 5-10% of yeast cells, increased to 20
      40% after 30 min-1 h and reached >70% before 2 h. FITC-IgY-Hp traversed the pores
      of Candida yeast cell wall and reached the vacuole where it bound with H. pylori
      antigens. Internalization of FITC-IgY-Hp was inhibited by low temperature, H2O2
      or acetic acid. It was concluded that internalization of FITC-IgY-Hp into yeast
      cell is a vital phenomenon and follows the endocytosis pathway. Furthermore, it
      was proposed that FITC-IgY-Hp internalization could be recruited for localization
      and identification of H. pylori inside the vacuole of Candida yeast. 

PMID- 25852653
TI  - Identification of a Novel Small Non-Coding RNA Modulating the Intracellular
      Survival of Brucella melitensis.
AB  - Bacterial small non-coding RNAs (sRNAs) are gene expression modulators respond to
      environmental changes, stressful conditions, and pathogenesis. In this study, by
      using a combined bioinformatic and experimental approach, eight novel sRNA genes
      were identified in intracellular pathogen Brucella melitensis. BSR0602, one sRNA
      that was highly induced in stationary phase, was further examined and found to
      modulate the intracellular survival of B. melitensis. BSR0602 was present at very
      high levels in vitro under stresses similar to those encountered during infection
      in host macrophages. Furthermore, BSR0602 was found to be highly expressed in the
      spleens of infected mice, suggesting its potential role in the control of
      pathogenesis. BSR0602 targets the mRNAs coding for gntR, a global transcriptional
      regulator, which is required for B. melitensis virulence. Overexpression of
      BSR0602 results in distinct reduction in the gntR mRNA level. B. melitensis with
      high level of BSR0602 is defective in bacteria intracellular survival in
      macrophages and defective in growth in the spleens of infected mice. Therefore,
      BSR0602 may directly inhibit the expression of gntR, which then impairs Brucellae
      intracellular survival and contributes to Brucella infection. Our findings
      suggest that BSR0602 is responsible for bacterial adaptation to stress conditions
      and thus modulate B. melitensis intracellular survival. 

PMID- 25852652
TI  - The genus Weissella: taxonomy, ecology and biotechnological potential.
AB  - Bacteria assigned to the genus Weissella are Gram-positive, catalase-negative,
      non-endospore forming cells with coccoid or rod-shaped morphology (Collins et
      al., 1993; Bjorkroth et al., 2009, 2014) and belong to the group of bacteria
      generally known as lactic acid bacteria. Phylogenetically, the Weissella belong
      to the Firmicutes, class Bacilli, order Lactobacillales and family
      Leuconostocaceae (Collins et al., 1993). They are obligately heterofermentative,
      producing CO2 from carbohydrate metabolism with either d(-)-, or a mixture of d(
      )- and l(+)- lactic acid and acetic acid as major end products from sugar
      metabolism. To date, there are 19 validly described Weissella species known.
      Weissella spp. have been isolated from and occur in a wide range of habitats,
      e.g., on the skin and in the milk and feces of animals, from saliva, breast milk,
      feces and vagina of humans, from plants and vegetables, as well as from a variety
      of fermented foods such as European sourdoughs and Asian and African traditional
      fermented foods. Thus, apart from a perceived technical role of certain Weissella
      species involved in such traditional fermentations, specific Weissella strains
      are also receiving attention as potential probiotics, and strain development of
      particularly W. cibaria strains is receiving attention because of their high
      probiotic potential for controlling periodontal disease. Moreover, W. confusa and
      W. cibaria strains are known to produce copius amounts of novel, non-digestible
      oligosaccharides and extracellular polysaccharides, mainly dextran. These
      polymers are receiving increased attention for their potential application as
      prebiotics and for a wide range of industrial applications, predominantly for
      bakeries and for the production of cereal-based fermented functional beverages.
      On the detrimental side, strains of certain Weissella species, e.g., of W.
      viridescens, W. cibaria and W. confusa, are known as opportunistic pathogens
      involved in human infections while strains of W. ceti have been recently
      recongnized as etiological agent of "weissellosis," which is a disease affecting
      farmed rainbow trouts. Bacteria belonging to this species thus are important both
      from a technological, as well as from a medical point of view, and both aspects
      should be taken into account in any envisaged biotechnological applications. 

PMID- 25852654
TI  - A new high-performance heterologous fungal expression system based on regulatory
      elements from the Aspergillus terreus terrein gene cluster.
AB  - Recently, the Aspergillus terreus terrein gene cluster was identified and
      selected for development of a new heterologous expression system. The cluster
      encodes the specific transcription factor TerR that is indispensable for terrein
      cluster induction. To identify TerR binding sites, different recombinant versions
      of the TerR DNA-binding domain were analyzed for specific motif recognition. The
      high affinity consensus motif TCGGHHWYHCGGH was identified from genes required
      for terrein production and binding site mutations confirmed their essential
      contribution to gene expression in A. terreus. A combination of TerR with its
      terA target promoter was tested as recombinant expression system in the
      heterologous host Aspergillus niger. TerR mediated target promoter activation was
      directly dependent on its transcription level. Therefore, terR was expressed
      under control of the regulatable amylase promoter PamyB and the resulting
      activation of the terA target promoter was compared with activation levels
      obtained from direct expression of reporters from the strong gpdA control
      promoter. Here, the coupled system outcompeted the direct expression system. When
      the coupled system was used for heterologous polyketide synthase expression high
      metabolite levels were produced. Additionally, expression of the Aspergillus
      nidulans polyketide synthase gene orsA revealed lecanoric acid rather than
      orsellinic acid as major polyketide synthase product. Domain swapping experiments
      assigned this depside formation from orsellinic acid to the OrsA thioesterase
      domain. These experiments confirm the suitability of the expression system
      especially for high-level metabolite production in heterologous hosts. 

PMID- 25852655
TI  - RNA shotgun metagenomic sequencing of northern California (USA) mosquitoes
      uncovers viruses, bacteria, and fungi.
AB  - Mosquitoes, most often recognized for the microbial agents of disease they may
      carry, harbor diverse microbial communities that include viruses, bacteria, and
      fungi, collectively called the microbiota. The composition of the microbiota can
      directly and indirectly affect disease transmission through microbial
      interactions that could be revealed by its characterization in natural
      populations of mosquitoes. Furthermore, the use of shotgun metagenomic sequencing
      (SMS) approaches could allow the discovery of unknown members of the microbiota.
      In this study, we use RNA SMS to characterize the microbiota of seven individual
      mosquitoes (species include Culex pipiens, Culiseta incidens, and Ochlerotatus
      sierrensis) collected from a variety of habitats in California, USA. Sequencing
      was performed on the Illumina HiSeq platform and the resulting sequences were
      quality-checked and assembled into contigs using the A5 pipeline. Sequences
      related to single stranded RNA viruses of the Bunyaviridae and Rhabdoviridae were
      uncovered, along with an unclassified genus of double-stranded RNA viruses.
      Phylogenetic analysis finds that in all three cases, the closest relatives of the
      identified viral sequences are other mosquito-associated viruses, suggesting
      widespread host-group specificity among disparate viral taxa. Interestingly, we
      identified a Narnavirus of fungi, also reported elsewhere in mosquitoes, that
      potentially demonstrates a nested host-parasite association between virus, fungi,
      and mosquito. Sequences related to 8 bacterial families and 13 fungal families
      were found across the seven samples. Bacillus and Escherichia/Shigella were
      identified in all samples and Wolbachia was identified in all Cx. pipiens
      samples, while no single fungal genus was found in more than two samples. This
      study exemplifies the utility of RNA SMS in the characterization of the natural
      microbiota of mosquitoes and, in particular, the value of identifying all
      microbes associated with a specific host. 

PMID- 25852658
TI  - Stable microbial community composition on the Greenland Ice Sheet.
AB  - The first molecular-based studies of microbes in snow and on glaciers have only
      recently been performed on the vast Greenland Ice Sheet (GrIS). Aeolian microbial
      seeding is hypothesized to impact on glacier surface community compositions.
      Localized melting of glacier debris (cryoconite) into the surface ice forms
      cryoconite holes, which are considered 'hot spots' for microbial activity on
      glaciers. To date, few studies have attempted to assess the origin and evolution
      of cryoconite and cryoconite hole communities throughout a melt season. In this
      study, a range of experimental approaches was used for the first time to study
      the inputs, temporal and structural transformations of GrIS microbial communities
      over the course of a whole ablation season. Small amounts of aeolian (wind and
      snow) microbes were potentially seeding the stable communities that were already
      present on the glacier (composed mainly of Proteobacteria, Cyanobacteria, and
      Actinobacteria). However, the dominant bacterial taxa in the aeolian samples
      (Firmicutes) did not establish themselves in local glacier surface communities.
      Cryoconite and cryoconite hole community composition remained stable throughout
      the ablation season following the fast community turnover, which accompanied the
      initial snow melt. The presence of stable communities in cryoconite and
      cryoconite holes on the GrIS will allow future studies to assess glacier surface
      microbial diversity at individual study sites from sampling intervals of short
      duration only. Aeolian inputs also had significantly different organic delta(13)C
      values (-28.0 to -27.00/00) from the glacier surface values (-25.7 to -23.60/00),
      indicating that in situ microbial processes are important in fixing new organic
      matter and transforming aeolian organic carbon. The continuous productivity of
      stable communities over one melt season makes them important contributors to
      biogeochemical nutrient cycling on glaciers. 

PMID- 25852657
TI  - Archaeal type IV pili and their involvement in biofilm formation.
AB  - Type IV pili are ancient proteinaceous structures present on the cell surface of
      species in nearly all bacterial and archaeal phyla. These filaments, which are
      required for a diverse array of important cellular processes, are assembled
      employing a conserved set of core components. While type IV pilins, the
      structural subunits of pili, share little sequence homology, their signal
      peptides are structurally conserved allowing for in silico prediction. Recently,
      in vivo studies in model archaea representing the euryarchaeal and crenarchaeal
      kingdoms confirmed that several of these pilins are incorporated into type IV
      adhesion pili. In addition to facilitating surface adhesion, these in vivo
      studies also showed that several predicted pilins are required for additional
      functions that are critical to biofilm formation. Examples include the subunits
      of Sulfolobus acidocaldarius Ups pili, which are induced by exposure to UV light
      and promote cell aggregation and conjugation, and a subset of the Haloferax
      volcanii adhesion pilins, which play a critical role in microcolony formation
      while other pilins inhibit this process. The recent discovery of novel pilin
      functions such as the ability of haloarchaeal adhesion pilins to regulate
      swimming motility may point to novel regulatory pathways conserved across
      prokaryotic domains. In this review, we will discuss recent advances in our
      understanding of the functional roles played by archaeal type IV adhesion pili
      and their subunits, with particular emphasis on their involvement in biofilm
      formation. 

PMID- 25852656
TI  - Redox regulation by reversible protein S-thiolation in bacteria.
AB  - Low molecular weight (LMW) thiols function as thiol-redox buffers to maintain the
      reduced state of the cytoplasm. The best studied LMW thiol is the tripeptide
      glutathione (GSH) present in all eukaryotes and Gram-negative bacteria.
      Firmicutes bacteria, including Bacillus and Staphylococcus species utilize the
      redox buffer bacillithiol (BSH) while Actinomycetes produce the related redox
      buffer mycothiol (MSH). In eukaryotes, proteins are post-translationally modified
      to S-glutathionylated proteins under conditions of oxidative stress. S
      glutathionylation has emerged as major redox-regulatory mechanism in eukaryotes
      and protects active site cysteine residues against overoxidation to sulfonic
      acids. First studies identified S-glutathionylated proteins also in Gram-negative
      bacteria. Advances in mass spectrometry have further facilitated the
      identification of protein S-bacillithiolations and S-mycothiolation as BSH- and
      MSH-mixed protein disulfides formed under oxidative stress in Firmicutes and
      Actinomycetes, respectively. In Bacillus subtilis, protein S-bacillithiolation
      controls the activities of the redox-sensing OhrR repressor and the methionine
      synthase MetE in vivo. In Corynebacterium glutamicum, protein S-mycothiolation
      was more widespread and affected the functions of the maltodextrin phosphorylase
      MalP and thiol peroxidase (Tpx). In addition, novel bacilliredoxins (Brx) and
      mycoredoxins (Mrx1) were shown to function similar to glutaredoxins in the
      reduction of BSH- and MSH-mixed protein disulfides. Here we review the current
      knowledge about the functions of the bacterial thiol-redox buffers glutathione,
      bacillithiol, and mycothiol and the role of protein S-thiolation in redox
      regulation and thiol protection in model and pathogenic bacteria. 

PMID- 25852659
TI  - Green materials science and engineering reduces biofouling: approaches for
      medical and membrane-based technologies.
AB  - Numerous engineered and natural environments suffer deleterious effects from
      biofouling and/or biofilm formation. For instance, bacterial contamination on
      biomedical devices pose serious health concerns. In membrane-based technologies,
      such as desalination and wastewater reuse, biofouling decreases membrane
      lifetime, and increases the energy required to produce clean water.
      Traditionally, approaches have combatted bacteria using bactericidal agents.
      However, due to globalization, a decline in antibiotic discovery, and the
      widespread resistance of microbes to many commercial antibiotics and metallic
      nanoparticles, new materials, and approaches to reduce biofilm formation are
      needed. In this mini-review, we cover the recent strategies that have been
      explored to combat microbial contamination without exerting evolutionary pressure
      on microorganisms. Renewable feedstocks, relying on structure-property
      relationships, bioinspired/nature-derived compounds, and green processing methods
      are discussed. Greener strategies that mitigate biofouling hold great potential
      to positively impact human health and safety. 

PMID- 25852660
TI  - The transcriptional response of microbial communities in thawing Alaskan
      permafrost soils.
AB  - Thawing of permafrost soils is expected to stimulate microbial decomposition and
      respiration of sequestered carbon. This could, in turn, increase atmospheric
      concentrations of greenhouse gasses, such as carbon dioxide and methane, and
      create a positive feedback to climate warming. Recent metagenomic studies suggest
      that permafrost has a large metabolic potential for carbon processing, including
      pathways for fermentation and methanogenesis. Here, we performed a pilot study
      using ultrahigh throughput Illumina HiSeq sequencing of reverse transcribed
      messenger RNA to obtain a detailed overview of active metabolic pathways and
      responsible organisms in up to 70 cm deep permafrost soils at a moist acidic
      tundra location in Arctic Alaska. The transcriptional response of the permafrost
      microbial community was compared before and after 11 days of thaw. In general,
      the transcriptional profile under frozen conditions suggests a dominance of
      stress responses, survival strategies, and maintenance processes, whereas upon
      thaw a rapid enzymatic response to decomposing soil organic matter (SOM) was
      observed. Bacteroidetes, Firmicutes, ascomycete fungi, and methanogens were
      responsible for largest transcriptional response upon thaw. Transcripts
      indicative of heterotrophic methanogenic pathways utilizing acetate, methanol,
      and methylamine were found predominantly in the permafrost table after thaw.
      Furthermore, transcripts involved in acetogenesis were expressed exclusively
      after thaw suggesting that acetogenic bacteria are a potential source of acetate
      for acetoclastic methanogenesis in freshly thawed permafrost. Metatranscriptomics
      is shown here to be a useful approach for inferring the activity of permafrost
      microbes that has potential to improve our understanding of permafrost SOM
      bioavailability and biogeochemical mechanisms contributing to greenhouse gas
      emissions as a result of permafrost thaw. 

PMID- 25852661
TI  - Isolation and characterization of plant growth-promoting rhizobacteria from wheat
      rhizosphere and their effect on plant growth promotion.
AB  - The present study was conducted to characterize the native plant growth promoting
      (PGP) bacteria from wheat rhizosphere and root-endosphere in the Himalayan region
      of Rawalakot, Azad Jammu and Kashmir (AJK), Pakistan. Nine bacterial isolates
      were purified, screened in vitro for PGP characteristics and evaluated for their
      beneficial effects on the early growth of wheat (Triticum aestivum L.). Among
      nine bacterial isolates, seven were able to produce indole-3- acetic acid in
      tryptophan-supplemented medium; seven were nitrogen fixer, and four were able to
      solubilize inorganic phosphate in vitro. Four different morphotypes were
      genotypically identified based on IGS-RFLP fingerprinting and representative of
      each morphotype was identified by 16S rRNA gene sequencing analysis except Gram
      positive putative Bacillus sp. Based on 16S rRNA gene sequence analysis,
      bacterial isolates AJK-3 and AJK-9 showing multiple PGP-traits were identified as
      Stenotrophomonas spp. while AJK-7 showed equal homologies to Acetobacter
      pasteurianus and Stenotrophomonas specie. Plant inoculation studies indicated
      that these Plant growth-promoting rhizobacteria (PGPR) strains provided a
      significant increase in shoot and root length, and shoot and root biomass. A
      significant increase in shoot N contents (up to 76%) and root N contents (up to
      32%) was observed over the un-inoculated control. The study indicates the
      potential of these PGPR for inoculums production or biofertilizers for enhancing
      growth and nutrient content of wheat and other crops under field conditions. The
      study is the first report of wheat associated bacterial diversity in the
      Himalayan region of Rawalakot, AJK. 

PMID- 25852663
TI  - Microbial methane formation in deep aquifers of a coal-bearing sedimentary basin,
      Germany.
AB  - Coal-bearing sediments are major reservoirs of organic matter potentially
      available for methanogenic subsurface microbial communities. In this study the
      specific microbial community inside lignite-bearing sedimentary basin in Germany
      and its contribution to methanogenic hydrocarbon degradation processes was
      investigated. The stable isotope signature of methane measured in groundwater and
      coal-rich sediment samples indicated methanogenic activity. Analysis of 16S rRNA
      gene sequences showed the presence of methanogenic Archaea, predominantly
      belonging to the orders Methanosarcinales and Methanomicrobiales, capable of
      acetoclastic or hydrogenotrophic methanogenesis. Furthermore, we identified
      fermenting, sulfate-, nitrate-, and metal-reducing, or acetogenic Bacteria
      clustering within the phyla Proteobacteria, complemented by members of the
      classes Actinobacteria, and Clostridia. The indigenous microbial communities
      found in the groundwater as well as in the coal-rich sediments are able to
      degrade coal-derived organic components and to produce methane as the final
      product. Lignite-bearing sediments may be an important nutrient and energy source
      influencing larger compartments via groundwater transport. 

PMID- 25852664
TI  - Disruption of mycorrhizal extraradical mycelium and changes in leaf water status
      and soil aggregate stability in rootbox-grown trifoliate orange.
AB  - Arbuscular mycorrhizas possess well developed extraradical mycelium (ERM) network
      that enlarge the surrounding soil for better acquisition of water and nutrients,
      besides soil aggregation. Distinction in ERM functioning was studied under a
      rootbox system, which consisted of root+hyphae and root-free hyphae compartments
      separated by 37-MUm nylon mesh with an air gap. Trifoliate orange (Poncirus
      trifoliata) seedlings were inoculated with Funneliformis mosseae in root+hyphae
      compartment, and the ERM network was established between the two compartments.
      The ERM network of air gap was disrupted before 8 h of the harvest (one time
      disruption) or multiple disruptions during seedlings acclimation. Our results
      showed that mycorrhizal inoculation induced a significant increase in growth
      (plant height, stem diameter, and leaf, stem, and root biomass) and physiological
      characters (leaf relative water content, leaf water potential, and transpiration
      rate), irrespective of ERM status. Easily-extractable glomalin-related soil
      protein (EE-GRSP) and total GRSP (T-GRSP) concentration and mean weight diameter
      (MWD, an indicator of soil aggregate stability) were significantly higher in
      mycorrhizosphere of root+hyphae and root-free hyphae compartments than non
      mycorrhizosphere. One time disruption of ERM network did not influence plant
      growth and soil properties but only notably decreased leaf water. Periodical
      disruption of ERM network at weekly interval markedly inhibited the mycorrhizal
      roles on plant growth, leaf water, GRSP production, and MWD in root+hyphae and
      hyphae chambers. EE-GRSP was the most responsive GRSP fraction to changes in leaf
      water and MWD under root+hyphae and hyphae conditions. It suggests that effect of
      peridical disruption of ERM network was more impactful than one-time disruption
      of ERM network with regard to leaf water, plant growth, and aggregate stability
      responses, thereby, implying ERM network aided in developing the host plant
      metabolically more active. 

PMID- 25852662
TI  - Genomic characteristics and environmental distributions of the uncultivated Far
      T4 phages.
AB  - Viral metagenomics (viromics) is a tremendous tool to reveal viral taxonomic and
      functional diversity across ecosystems ranging from the human gut to the world's
      oceans. As with microbes however, there appear vast swaths of "dark matter" yet
      to be documented for viruses, even among relatively well-studied viral types.
      Here, we use viromics to explore the "Far-T4 phages" sequence space, a neighbor
      clade from the well-studied T4-like phages that was first detected through PCR
      study in seawater and subsequently identified in freshwater lakes through 454
      sequenced viromes. To advance the description of these viruses beyond this single
      marker gene, we explore Far-T4 genome fragments assembled from two deeply
      sequenced freshwater viromes. Single gene phylogenetic trees confirm that the Far
      T4 phages are divergent from the T4-like phages, genome fragments reveal largely
      collinear genome organizations, and both data led to the delineation of five Far
      T4 clades. Three-dimensional models of major capsid proteins are consistent with
      a T4-like structure, and highlight a highly conserved core flanked by variable
      insertions. Finally, we contextualize these now better characterized Far-T4
      phages by re-analyzing 196 previously published viromes. These suggest that Far
      T4 are common in freshwater and seawater as only four of 82 aquatic viromes
      lacked Far-T4-like sequences. Variability in representation across the five newly
      identified clades suggests clade-specific niche differentiation may be occurring
      across the different biomes, though the underlying mechanism remains
      unidentified. While complete genome assembly from complex communities and the
      lack of host linkage information still bottleneck virus discovery through
      viromes, these findings exemplify the power of metagenomics approaches to assess
      the diversity, evolutionary history, and genomic characteristics of novel
      uncultivated phages. 

PMID- 25852665
TI  - Insights into the environmental reservoir of pathogenic Vibrio parahaemolyticus
      using comparative genomics.
AB  - Vibrio parahaemolyticus is an aquatic halophilic bacterium that occupies
      estuarine and coastal marine environments, and is a leading cause of seafood
      borne food poisoning cases. To investigate the environmental reservoir and
      potential gene flow that occurs among V. parahaemolyticus isolates, the virulence
      associated gene content and genome diversity of a collection of 133 V.
      parahaemolyticus isolates were analyzed. Phylogenetic analysis of housekeeping
      genes, and pulsed-field gel electrophoresis, demonstrated that there is genetic
      similarity among V. parahaemolyticus clinical and environmental isolates. Whole
      genome sequencing and comparative analysis of six representative V.
      parahaemolyticus isolates was used to identify genes that are unique to the
      clinical and environmental isolates examined. Comparative genomics demonstrated
      an O3:K6 environmental isolate, AF91, which was cultured from sediment collected
      in Florida in 2006, has significant genomic similarity to the post-1995 O3:K6
      isolates. However, AF91 lacks the majority of the virulence-associated genes and
      genomic islands associated with these highly virulent post-1995 O3:K6 genomes.
      These findings demonstrate that although they do not contain most of the known
      virulence-associated regions, some V. parahaemolyticus environmental isolates
      exhibit significant genetic similarity to clinical isolates. This highlights the
      dynamic nature of the V. parahaemolyticus genome allowing them to transition
      between aquatic and host-pathogen states. 

PMID- 25852666
TI  - Silver linings: a personal memoir about Hurricane Katrina and fungal volatiles.
AB  - In the aftermath of Hurricane Katrina, the levees protecting New Orleans,
      Louisiana failed. Because approximately 80% of the city was under sea level,
      widespread flooding ensued. As a resident of New Orleans who had evacuated before
      the storm and a life-long researcher on filamentous fungi, I had known what to
      expect. After the hurricane I traveled home with a suitcase full of Petri dishes
      and sampling equipment so as to study the fungi that were "eating my house." Not
      only were surfaces covered with fungal growth, the air itself was full of
      concentrated mold odor, a smell that was orders of magnitude more funky than any
      damp, musty basement I had ever encountered. The smell made me feel bad and I had
      to take regular breaks as I sampled. Being a mycotoxin expert, I knew a fair
      amount about "sick building syndrome" but believed that it was difficult to get
      enough respiratory exposure to toxins to cause the array of symptoms associated
      with the syndrome. So why was I feeling sick? Some Scandinavian experts had
      hypothesized that mold volatile organic compounds (VOCs) might be the fungal
      metabolites to blame for sick building syndrome and the time in my smelly, mold
      infested home made me think they might be right. After securing a new job and
      establishing a new laboratory, I endeavored to test the hypothesis that some
      volatile mold metabolites might be toxic. My laboratory at Rutgers University has
      interrogated the role of VOCs in possible interkingdom toxicity by developing
      controlled microcosms for exposing simple genetic model organisms to the vapor
      phase of growing fungi. Both Arabidopsis thaliana and Drosophila melanogaster
      exhibit a range of toxic symptoms that vary with the species of fungus, the
      duration of exposure, and other experimental parameters. Moreover, low
      concentrations of chemical standards of individual fungal VOCs such as 1-octen-3
      ol also exhibit varying toxicity and cause neurotoxicity in a Drosophila model.
      Collectively, these data suggest that fungal VOCs may contribute to some of the
      adverse health effects reported by people exposed to damp indoor environments and
      that biogenic gas phase molecules deserve increased attention by the research
      community. 

PMID- 25852667
TI  - Isolation and identification of indigenous plant growth promoting rhizobacteria
      from Himalayan region of Kashmir and their effect on improving growth and
      nutrient contents of maize (Zea mays L.).
AB  - Introduction and exploitation of plant growth promoting rhizobacteria (PGPR) in
      agro-ecosystems enhance plant-microbes interactions that may affect ecosystems
      sustainability, agricultural productivity, and environmental quality. The present
      study was conducted to isolate and identify PGPRs associated with maize (Zea mays
      L.) from twenty sites of Himalayan region of Hajira-Rawalakot, Azad Jammu and
      Kashmir (AJK), Pakistan. A total of 100 isolates were isolated from these sites,
      out of which eight (HJR1, HJR2, HJR3, HJR4, HJR5, MR6, HJR7, HJR8) were selected
      in vitro for their plant growth promoting ability (PGPA) including phosphorus
      solubilization, indole-3-acetic acid (IAA) production and N2 fixation. The 16S
      rRNA gene sequencing technique was used for molecular identity and
      authentication. Isolates were then further tested for their effects on growth and
      nutrient contents of maize (Z. mays L.) under pouch and pot conditions. The 16S
      rRNA gene sequencing and phylogenetic analysis identified these isolates belong
      to Pseudomonas and Bacillus genera. The isolates promoted plant growth by
      solubilizing soil P which ranged between 19.2 and 35.6 MUg mL(-1). The isolates
      HJR1, HJR2, HJR3, and HJR5 showed positive activity in acetylene reduction assay
      showing their N2-fixation potential. All eight isolates showed the potential to
      produce IAA in the range of 0.9-5.39 MUg mL(-1) and promote plant growth. Results
      from a subsequent pot experiment indicated PGPRs distinctly increased maize shoot
      and root length, shoot and root dry weight, root surface area, leaf surface area,
      shoot and root N and P contents. Among the eight isolates, HR3 showed a marked P
      solubilizing activity, plant growth-promoting attributes, and the potential to be
      developed as a biofertilizers for integrated nutrient management strategies. 

PMID- 25852669
TI  - Development of a bacterial bioassay for atrazine and cyanuric acid detection.
AB  - The s-triazine herbicides are compounds which can disseminate into soils and
      water. Due to their toxic effects on living organisms, their concentrations in
      drinking water are legislated by WHO recommendations. Here we have developed for
      the first time, to the best of our knowledge, an alternative method for
      physicochemical quantification using two bioluminescent bacterial biosensors: E.
      coli SM003 for cyanuric acid detection and E. coli SM004 for both atrazine and
      cyanuric acid detection. The concentration of cyanuric acid detection for E. coli
      SM003 ranges from 7.83 MUM to 2.89 mM, and for E. coli SM004 ranges from 0.22 to
      15 MUM. Moreover, atrazine detection by E. coli SM004 ranges from 1.08 to 15 MUM.
      According to WHO recommendations, the cyanuric acid detection range is sensitive
      enough to discriminate between polluted and drinking water. Nevertheless, the
      detection of atrazine by E. coli SM004 is only applicable for high concentrations
      of contaminants. 

PMID- 25852668
TI  - Influence of Martian regolith analogs on the activity and growth of methanogenic
      archaea, with special regard to long-term desiccation.
AB  - Methanogenic archaea have been studied as model organisms for possible life on
      Mars for several reasons: they can grow lithoautotrophically by using hydrogen
      and carbon dioxide as energy and carbon sources, respectively; they are
      anaerobes; and they evolved at a time when conditions on early Earth are believed
      to have looked similar to those of early Mars. As Mars is currently dry and cold
      and as water might be available only at certain time intervals, any organism
      living on this planet would need to cope with desiccation. On Earth there are
      several regions with low water availability as well, e.g., permafrost
      environments, desert soils, and salt pans. Here, we present the results of a set
      of experiments investigating the influence of different Martian regolith analogs
      (MRAs) on the metabolic activity and growth of three methanogenic strains exposed
      to culture conditions as well as long-term desiccation. In most cases,
      concentrations below 1 wt% of regolith in the media resulted in an increase of
      methane production rates, whereas higher concentrations decreased the rates, thus
      prolonging the lag phase. Further experiments showed that methanogenic archaea
      are capable of producing methane when incubated on a water-saturated sedimentary
      matrix of regolith lacking nutrients. Survival of methanogens under these
      conditions was analyzed with a 400 day desiccation experiment in the presence of
      regolith analogs. All tested strains of methanogens survived the desiccation
      period as it was determined through reincubation on fresh medium and via qPCR
      following propidium monoazide treatment to identify viable cells. The survival of
      long-term desiccation and the ability of active metabolism on water-saturated
      MRAs strengthens the possibility of methanogenic archaea or physiologically
      similar organisms to exist in environmental niches on Mars. The best results were
      achieved in presence of a phyllosilicate, which provides insights of possible
      positive effects in habitats on Earth as well. 

PMID- 25852672
TI  - Commentary on: "Detection of Toxoplasma gondii in raw caprine, ovine, buffalo,
      bovine, and camel milk using cell cultivation, cat bioassay, capture ELISA, and
      PCR methods in Iran".

PMID- 25852671
TI  - Systems modeling approaches for microbial community studies: from metagenomics to
      inference of the community structure.
AB  - Microbial communities play important roles in health, industrial applications and
      earth's ecosystems. With current molecular techniques we can characterize these
      systems in unprecedented detail. However, such methods provide little mechanistic
      insight into how the genetic properties and the dynamic couplings between
      individual microorganisms give rise to their dynamic activities. Neither do they
      give insight into what we call "the community state", that is the fluxes and
      concentrations of nutrients within the community. This knowledge is a
      prerequisite for rational control and intervention in microbial communities.
      Therefore, the inference of the community structure from experimental data is a
      major current challenge. We will argue that this inference problem requires
      mathematical models that can integrate heterogeneous experimental data with
      existing knowledge. We propose that two types of models are needed. Firstly,
      mathematical models that integrate existing genomic, physiological, and
      physicochemical information with metagenomics data so as to maximize information
      content and predictive power. This can be achieved with the use of constraint
      based genome-scale stoichiometric modeling of community metabolism which is
      ideally suited for this purpose. Next, we propose a simpler coarse-grained model,
      which is tailored to solve the inference problem from the experimental data. This
      model unambiguously relate to the more detailed genome-scale stoichiometric
      models which act as heterogeneous data integrators. The simpler inference models
      are, in our opinion, key to understanding microbial ecosystems, yet until now,
      have received remarkably little attention. This has led to the situation where
      the modeling of microbial communities, using only genome-scale models is
      currently more a computational, theoretical exercise than a method useful to the
      experimentalist. 

PMID- 25852670
TI  - Surfactants tailored by the class Actinobacteria.
AB  - Globally the change towards the establishment of a bio-based economy has resulted
      in an increased need for bio-based applications. This, in turn, has served as a
      driving force for the discovery and application of novel biosurfactants. The
      class Actinobacteria represents a vast group of microorganisms with the ability
      to produce a diverse range of secondary metabolites, including surfactants.
      Understanding the extensive nature of the biosurfactants produced by
      actinobacterial strains can assist in finding novel biosurfactants with new
      potential applications. This review therefore presents a comprehensive overview
      of the knowledge available on actinobacterial surfactants, the chemical
      structures that have been completely or partly elucidated, as well as the
      identity of the biosurfactant-producing strains. Producer strains of not yet
      elucidated compounds are discussed, as well as the original habitats of all the
      producer strains, which seems to indicate that biosurfactant production is
      environmentally driven. Methodology applied in the isolation, purification and
      structural elucidation of the different types of surface active compounds, as
      well as surfactant activity tests, are also discussed. Overall, actinobacterial
      surfactants can be summarized to include the dominantly occurring trehalose
      comprising surfactants, other non-trehalose containing glycolipids, lipopeptides
      and the more rare actinobacterial surfactants. The lack of structural information
      on a large proportion of actinobacterial surfactants should be considered as a
      driving force to further explore the abundance and diversity of these compounds.
      This would allow for a better understanding of actinobacterial surface active
      compounds and their potential for biotechnological application. 

PMID- 25852673
TI  - Drugs of Abuse in HIV infection and neurotoxicity.

PMID- 25852674
TI  - Beyond the iron age: the ecological relevance of non-ferrous bioactive trace
      metals and organic growth factors in aquatic systems.

PMID- 25852676
TI  - Effect of Puumala hantavirus infection on human umbilical vein endothelial cell
      hemostatic function: platelet interactions, increased tissue factor expression
      and fibrinolysis regulator release.
AB  - Puumala virus (PUUV) infection causes over 5000 cases of hemorrhagic fever in
      Europe annually and can influence the hemostatic balance extensively. Infection
      might lead to hemorrhage, while a recent study showed an increased risk of
      myocardial infarction during or shortly after PUUV infection. The mechanism by
      which this hantavirus influences the coagulation system remains unknown.
      Therefore we aimed to elucidate mechanisms explaining alterations seen in primary
      and secondary hemostasis during PUUV infection. By using low passage PUUV
      isolates to infect primary human umbilical vein endothelial cells (HUVECs) we
      were able to show alterations in the regulation of primary- and secondary
      hemostasis and in the release of fibrinolysis regulators. Our main finding was an
      activation of secondary hemostasis due to increased tissue factor (TF) expression
      leading to increased thrombin generation in a functional assay. Furthermore, we
      showed that during infection platelets adhered to HUVEC and subsequently
      specifically to PUUV virus particles. Infection of HUVEC with PUUV did not result
      in increased von Willebrand factor while they produced more plasminogen activator
      inhibitor type-1 (PAI-1) compared to controls. The PAI-1 produced in this model
      formed complexes with vitronectin. This is the first report that reveals a
      potential mechanism behind the pro-coagulant changes in PUUV patients, which
      could be the result of increased thrombin generation due to an increased TF
      expression on endothelial cells during infection. Furthermore, we provide insight
      into the contribution of endothelial cell responses regarding hemostasis in PUUV
      pathogenesis. 

PMID- 25852675
TI  - The composition of the global and feature specific cyanobacterial core-genomes.
AB  - Cyanobacteria are photosynthetic prokaryotes important for many ecosystems with a
      high potential for biotechnological usage e.g., in the production of bioactive
      molecules. Either asks for a deep understanding of the functionality of
      cyanobacteria and their interaction with the environment. This in part can be
      inferred from the analysis of their genomes or proteomes. Today, many
      cyanobacterial genomes have been sequenced and annotated. This information can be
      used to identify biological pathways present in all cyanobacteria as proteins
      involved in such processes are encoded by a so called core-genome. However,
      beside identification of fundamental processes, genes specific for certain
      cyanobacterial features can be identified by a holistic genome analysis as well.
      We identified 559 genes that define the core-genome of 58 analyzed cyanobacteria,
      as well as three genes likely to be signature genes for thermophilic and 57 genes
      likely to be signature genes for heterocyst-forming cyanobacteria. To get
      insights into cyanobacterial systems for the interaction with the environment we
      also inspected the diversity of the outer membrane proteome with focus on beta
      barrel proteins. We observed that most of the transporting outer membrane beta
      barrel proteins are not globally conserved in the cyanobacterial phylum. In turn,
      the occurrence of beta-barrel proteins shows high strain specificity. The core
      set of outer membrane proteins globally conserved in cyanobacteria comprises
      three proteins only, namely the outer membrane beta-barrel assembly protein
      Omp85, the lipid A transfer protein LptD, and an OprB-type porin. Thus, we
      conclude that cyanobacteria have developed individual strategies for the
      interaction with the environment, while other intracellular processes like the
      regulation of the protein homeostasis are globally conserved. 

PMID- 25852677
TI  - A pandemic Vibrio parahaemolyticus O3:K6 clone causing most associated diarrhea
      cases in the Pacific Northwest coast of Mexico.
AB  - Between September and October of 2004, more than 1230 cases of gastroenteritis
      due to pandemic O3:K6 strains of Vibrio parahaemolyticus (V. parahaemolyticus)
      were reported in the relatively small geographical area of Southern Sinaloa, a
      state located in Northwest Mexico. Since then, V. parahaemolyticus-associated
      gastroenteritis cases have gradually increased in prevalence spreading from south
      to north. The present study conducted an epidemiological surveillance of V.
      parahaemolyticus strains in both environmental and clinical samples along the
      Pacific coast of Sinaloa from 2011 to 2013. The genetic relatedness, serotype
      dominance and antibiotic resistance of isolates were investigated. A total of 46
      strains were isolated from environmental samples (e.g., sediment, seawater and
      shrimp), whereas 249 strains were obtained from stools of patients with
      gastroenteritis. Nine different O serogroups and 16 serovars were identified.
      Serovars O3:K6 and O6:K46 were identified in both environmental and clinical
      strains. Whereas most environmental isolates carried the tdh gene (71.74%,
      33/46), only three (6.52%) belonged to pandemic clones (O3:K6, O3:KUT and
      OUT:KUT). In contrast, 81.1% (202/249) of clinical isolates belonged to pandemic
      serotypes, with O3:K6 (tdh, toxRS/new, and/or orf8) representing the predominant
      serovar (97%, 196/202). This prevalence of pathogenic (tdh and/or trh positive)
      and O3:K6 pandemic V. parahaemolyticus isolates in this study were similar to
      those found from 2004 to 2010. As investigated by REP-PCR, genetic lineages of
      selected O3:K6 strains isolated in this study and some isolated earlier were
      nearly identical. Antimicrobial susceptibility testing showed that most strains
      (93.8%) were resistant to ampicillin but sensitive to chloramphenicol (98.8%).
      Multidrug resistance significantly increased from 8.6% (2004-2010) to 22.93%
      (2011-2013; p < 0.05). Our data indicate that pandemic O3:K6 clone has
      endemically established in the Pacific Coast of Mexico. 

PMID- 25852678
TI  - Microbial abundance in surface ice on the Greenland Ice Sheet.
AB  - Measuring microbial abundance in glacier ice and identifying its controls is
      essential for a better understanding and quantification of biogeochemical
      processes in glacial ecosystems. However, cell enumeration of glacier ice samples
      is challenging due to typically low cell numbers and the presence of interfering
      mineral particles. We quantified for the first time the abundance of microbial
      cells in surface ice from geographically distinct sites on the Greenland Ice
      Sheet (GrIS), using three enumeration methods: epifluorescence microscopy (EFM),
      flow cytometry (FCM), and quantitative polymerase chain reaction (qPCR). In
      addition, we reviewed published data on microbial abundance in glacier ice and
      tested the three methods on artificial ice samples of realistic cell (10(2)-10(7)
      cells ml(-1)) and mineral particle (0.1-100 mg ml(-1)) concentrations, simulating
      a range of glacial ice types, from clean subsurface ice to surface ice to
      sediment-laden basal ice. We then used multivariate statistical analysis to
      identify factors responsible for the variation in microbial abundance on the ice
      sheet. EFM gave the most accurate and reproducible results of the tested
      methodologies, and was therefore selected as the most suitable technique for cell
      enumeration of ice containing dust. Cell numbers in surface ice samples,
      determined by EFM, ranged from ~ 2 * 10(3) to ~ 2 * 10(6) cells ml(-1) while dust
      concentrations ranged from 0.01 to 2 mg ml(-1). The lowest abundances were found
      in ice sampled from the accumulation area of the ice sheet and in samples
      affected by fresh snow; these samples may be considered as a reference point of
      the cell abundance of precipitants that are deposited on the ice sheet surface.
      Dust content was the most significant variable to explain the variation in the
      abundance data, which suggests a direct association between deposited dust
      particles and cells and/or by their provision of limited nutrients to microbial
      communities on the GrIS. 

PMID- 25852679
TI  - rpoN1, but not rpoN2, is required for twitching motility, natural competence,
      growth on nitrate, and virulence of Ralstonia solanacearum.
AB  - The plant pathogen Ralstonia solanacearum has two genes encoding for the sigma
      factor sigma(54): rpoN1, located in the chromosome and rpoN2, located in a
      distinct "megaplasmid" replicon. In this study, individual mutants as well as a
      double mutant of rpoN were created in R. solanacearum strain GMI1000 in order to
      determine the extent of functional overlap between these two genes. By virulence
      assay we observed that rpoN1 is required for virulence whereas rpoN2 is not. In
      addition rpoN1 controls other important functions such twitching motility,
      natural transformation and growth on nitrate, unlike rpoN2. The rpoN1 and rpoN2
      genes have different expression pattern, the expression of rpoN1 being
      constitutive whereas rpoN2 expression is induced in minimal medium and in the
      presence of plant cells. Moreover, the expression of rpoN2 is dependent upon
      rpoN1. Our work therefore reveals that the two rpoN genes are not functionally
      redundant in R. solanacearum. A list of potential sigma(54) targets was
      identified in the R. solanacearum genome and suggests that multiple traits are
      under the control of these regulators. Based on these findings, we provide a
      model describing the functional connection between RpoN1 and the PehR
      pathogenicity regulator and their dual role in the control of several R.
      solanacearum virulence determinants. 

PMID- 25852680
TI  - Structural and molecular determinants of HIV-1 Gag binding to the plasma
      membrane.
AB  - Targeting of the Gag polyprotein to the plasma membrane (PM) for assembly is a
      critical event in the late phase of immunodeficiency virus type-1 (HIV-1)
      infection. Gag binding to the PM is mediated by interactions between the
      myristoylated matrix (MA) domain and PM lipids. Despite the extensive biochemical
      and in vitro studies of Gag and MA binding to membranes over the last two
      decades, the discovery of the role of phosphatidylinositol-4,5-bisphosphate
      [PI(4,5)P2] in Gag binding to the PM has sparked a string of studies aimed at
      elucidating the molecular mechanism of retroviral Gag-PM binding. Electrostatic
      interactions between a highly conserved basic region of MA and acidic
      phospholipids have long been thought to be the main driving force for Gag
      membrane interactions. However, recent studies suggest that the mechanism is
      rather complex since other factors such as the hydrophobicity of the membrane
      interior represented by the acyl chains and cholesterol also play important
      roles. Here we summarize the current understanding of HIV-1 Gag-membrane
      interactions at the molecular and structural levels and briefly discuss the
      underlying forces governing interactions of other retroviral MA proteins with the
      PM. 

PMID- 25852681
TI  - Environmental and metabolic sensors that control T cell biology.
AB  - The T lymphocyte response to pathogens is shaped by the microenvironment.
      Environmental sensors in T cells include the nutrient-sensing serine/threonine
      kinases, adenosine monophosphate-activated protein kinase and mammalian target of
      rapamycin complex 1. Other environmental sensors are transcription factors such
      as hypoxia-inducible factor-1 and the aryl hydrocarbon receptor. The present
      review explores the molecular basis for the impact of environmental signals on
      the differentiation of conventional T cell receptor alphabeta T cells and how the
      T cell response to immune stimuli can coordinate the T cell response to
      environmental cues. 

PMID- 25852684
TI  - The genomic load of deleterious mutations: relevance to death in infancy and
      childhood.
AB  - The human diploid genome has approximately 40,000 functioning conserved genes
      distributed within 6 billion base pairs of DNA. Most individuals carry a few
      heterozygous deleterious mutations and this leads to an increased risk of
      recessive disease in the offspring of cousin unions. Rare recessive disease is
      more common in the children of cousin marriages than in the general population,
      even though <1% of marriages in the Western World are between first cousins. But
      more than 90% of the children of cousin marriages do not have recessive disease
      and are as healthy as the rest of the population. A mathematical model based on
      these observations generates simultaneous equations linking the mean number of
      deleterious mutations in the genome of adults (M), the mean number of new
      deleterious mutations arising in gametogenesis and passed to the next generation
      (N) and the number of genes in the human diploid genome (L). The best estimates
      are that M is <7 and N is approximately 1. The nature of meiosis indicates that
      deleterious mutations in zygotes will have a Poisson distribution with a mean of
      M + N. There must be strong selective pressure against zygotes at the upper end
      of the Poisson distribution otherwise the value of M would rise with each
      generation. It is suggested that this selection is based on synergistic
      interaction of heterozygous deleterious mutations acting in large complex highly
      redundant and robust genetic networks. To maintain the value of M in single
      figures over many thousands of generations means that the zygote loss must be of
      the order of 30%. Most of this loss will occur soon after conception but some
      will occur later; during fetal development, in infancy and even in childhood.
      Selection means genetic death and this is caused by disease to which the
      deleterious mutations predispose. In view of this genome sequencing should be
      undertaken in all infant deaths in which the cause of death is not ascertained by
      standard techniques. 

PMID- 25852683
TI  - Innate immune activation by tissue injury and cell death in the setting of
      hematopoietic stem cell transplantation.
AB  - Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) with donor
      lymphocyte infusion is the mainstay of treatment for many types of hematological
      malignancies, but the therapeutic effect and prevention of relapse is complicated
      by donor T-cell recognition and attack of host tissue in a process known as graft
      versus-host disease (GvHD). Cytotoxic myeloablative conditioning regimens used
      prior to Allo-HSCT result in the release of endogenous innate immune activators
      that are increasingly recognized for their role in creating a pro-inflammatory
      milieu. This increased inflammatory state promotes allogeneic T-cell activation
      and the induction and perpetuation of GvHD. Here, we review the processes of
      cellular response to injury and cell death that are relevant following Allo-HSCT
      and present the current evidence for a causative role of a variety of endogenous
      innate immune activators in the mediation of sterile inflammation following Allo
      HSCT. Finally, we discuss the potential therapeutic strategies that target the
      endogenous pathways of innate immune activation to decrease the incidence and
      severity of GvHD following Allo-HSCT. 

PMID- 25852685
TI  - Commentary on: Antibody and B Cell Responses to Plasmodium Sporozoites.

PMID- 25852687
TI  - DFS70/LEDGFp75: An Enigmatic Autoantigen at the Interface between Autoimmunity,
      AIDS, and Cancer.
AB  - Clinical and diagnostic laboratories often encounter patient sera containing
      antinuclear antibodies (ANAs) that produce a nuclear dense fine speckled
      immunofluorescence pattern on HEp-2 cells. These autoantibodies usually target
      the dense fine speckled protein of 70 kDa (DFS70), commonly known as lens
      epithelium-derived growth factor p75 (LEDGFp75). Anti-DFS70/LEDGFp75
      autoantibodies have recently attracted much interest because of their relatively
      common occurrence in sera from patients with positive ANA tests with no clinical
      evidence of systemic autoimmune rheumatic disease (SARD). Their presence has been
      documented primarily in patients with diverse non-SARD inflammatory conditions
      and "apparently healthy" individuals. While there is circumstantial evidence that
      depending on the context these autoantibodies could play protective, pathogenic,
      or sensor roles, their significance remains elusive. DFS70/LEDGFp75 has emerged
      during the past decade as a stress transcription co-activator relevant to HIV
      integration, cancer, and inflammation. It is not clear, however, what makes this
      protein the target of such a common autoantibody response. We suggest that a
      better understanding of DFS70/LEDGFp75 biology is key to elucidating the
      significance of its associated autoantibodies. Here, we discuss briefly our
      current understanding of this enigmatic autoantigen and potential scenarios
      leading to its targeting by the immune system. 

PMID- 25852686
TI  - An evolutionary history of defensins: a role for copy number variation in
      maximizing host innate and adaptive immune responses.
AB  - Defensins represent an evolutionary ancient family of antimicrobial peptides that
      play diverse roles in human health and disease. Defensins are cationic cysteine
      containing multifunctional peptides predominantly expressed by epithelial cells
      or neutrophils. Defensins play a key role in host innate immune responses to
      infection and, in addition to their classically described role as antimicrobial
      peptides, have also been implicated in immune modulation, fertility, development,
      and wound healing. Aberrant expression of defensins is important in a number of
      inflammatory diseases as well as modulating host immune responses to bacteria,
      unicellular pathogens, and viruses. In parallel with their role in immunity, in
      other species, defensins have evolved alternative functions, including the
      control of coat color in dogs. Defensin genes reside in complex genomic regions
      that are prone to structural variations and some defensin family members exhibit
      copy number variation (CNV). Structural variations have mediated, and continue to
      influence, the diversification and expression of defensin family members. This
      review highlights the work currently being done to better understand the genomic
      architecture of the beta-defensin locus. It evaluates current evidence linking
      defensin CNV to autoimmune disease (i.e., Crohn's disease and psoriasis) as well
      as the contribution CNV has in influencing immune responses to HIV infection. 

PMID- 25852688
TI  - A Highly Focused Antigen Receptor Repertoire Characterizes gammadelta T Cells
      That are Poised to Make IL-17 Rapidly in Naive Animals.
AB  - Interleukin (IL)-17 plays a key role in immunity. In acute infections, a rapid IL
      17 response must be induced without prior antigen exposure, and gammadelta T
      cells are the major initial IL-17 producers. In fact, some gammadelta T cells
      make IL-17 within hours after an immune challenge. These cells appear to acquire
      the ability to respond to IL-1 and IL-23 and to make IL-17 naturally in naive
      animals. They are known as the natural Tgammadelta17 (nTgammadelta17) cells. The
      rapidity of the nTgammadelta17 response, and the apparent lack of explicit T cell
      receptor (TCR) engagement for its induction have led to the view that this is a
      cytokine (IL-1, IL-23)-mediated response. However, pharmacological inhibition or
      genetic defects in TCR signaling drastically reduce the nTgammadelta17 response
      and/or their presence. To better understand antigen recognition in this rapid IL
      17 response, we analyzed the antigen receptor repertoire of IL-1R(+)/IL-23R(+)
      gammadelta T cells, a proxy for nTgammadelta17 cells in naive animals directly ex
      vivo, using a barcode-enabled high throughput single-cell TCR sequence analysis.
      We found that regardless of their anatomical origin, these cells have a highly
      focused TCR repertoire. In particular, the TCR sequences have limited V gene
      combinations, little or no junctional diversity and much reduced or no N region
      diversity. In contrast, IL-23R(-) cells at mucosal sites similar to most of the
      splenic gammadelta T cells and small intestine epithelial gammadelta lymphocytes
      expressed diverse TCRs. This remarkable commonality and restricted repertoire of
      IL-1R(+)/IL-23R(+) gammadelta T cells underscores the importance of antigen
      recognition in their establishment/function. 

PMID- 25852682
TI  - Vitamin D Actions on CD4(+) T Cells in Autoimmune Disease.
AB  - This review summarizes and integrates research on vitamin D and CD4(+) T
      lymphocyte biology to develop new mechanistic insights into the molecular
      etiology of autoimmune disease. A deep understanding of molecular mechanisms
      relevant to gene-environment interactions is needed to deliver etiology-based
      autoimmune disease prevention and treatment strategies. Evidence linking
      sunlight, vitamin D, and the risk of multiple sclerosis and type 1 diabetes is
      summarized to develop the thesis that vitamin D is the environmental factor that
      most strongly influences autoimmune disease development. Evidence for CD4(+) T
      cell involvement in autoimmune disease pathogenesis and for paracrine calcitriol
      signaling to CD4(+) T lymphocytes is summarized to support the thesis that
      calcitriol is sunlight's main protective signal transducer in autoimmune disease
      risk. Animal modeling and human mechanistic data are summarized to support the
      view that vitamin D probably influences thymic negative selection, effector Th1
      and Th17 pathogenesis and responsiveness to extrinsic cell death signals,
      FoxP3(+)CD4(+) T-regulatory cell and CD4(+) T-regulatory cell type 1 (Tr1) cell
      functions, and a Th1-Tr1 switch. The proposed Th1-Tr1 switch appears to bridge
      two stable, self-reinforcing immune states, pro- and anti-inflammatory, each with
      a characteristic gene regulatory network. The bi-stable switch would enable T
      cells to integrate signals from pathogens, hormones, cell-cell interactions, and
      soluble mediators and respond in a biologically appropriate manner. Finally,
      unanswered questions and potentially informative future research directions are
      highlighted to speed delivery of etiology-based strategies to reduce autoimmune
      disease. 

PMID- 25852689
TI  - Adeno-Associated Viral Vectors at the Frontier between Tolerance and Immunity.

PMID- 25852690
TI  - Killer B lymphocytes and their fas ligand positive exosomes as inducers of immune
      tolerance.
AB  - Induction of immune tolerance is a key process by which the immune system is
      educated to modulate reactions against benign stimuli such as self-antigens and
      commensal microbes. Understanding and harnessing the natural mechanisms of immune
      tolerance may become an increasingly useful strategy for treating many types of
      allergic and autoimmune diseases, as well as for improving the acceptance of
      solid organ transplants. Our laboratory and others have been interested in the
      natural ability of some B lymphocytes to express the death-inducing molecule Fas
      ligand (FasL), and their ability to kill T helper (TH) lymphocytes. We have
      recently shown that experimental transformation of human B cells by a non
      replicative variant of Epstein-Barr virus (EBV) consistently resulted in high
      expression of functional FasL protein. The production and release of FasL(+)
      exosomes that co-expressed major histocompatibility complex (MHC) class II
      molecules and had the capacity to kill antigen-specific TH cells was also
      observed. Several lines of evidence indicate that FasL+ B cells and
      FasL(+)MHCII(+) exosomes have important roles in natural immune tolerance and
      have a great deal of therapeutic potential. Taken together, these findings
      suggest that EBV-immortalized human B lymphoblastoid cell lines could be used as
      cellular factories for FasL(+) exosomes, which would be employed to
      therapeutically establish and/or regain immune tolerance toward specific
      antigens. The goals of this review are to summarize current knowledge of the
      roles of FasL(+) B cells and exosomes in immune regulation, and to suggest
      methods of manipulating killer B cells and FasL(+) exosomes for clinical
      purposes. 

PMID- 25852692
TI  - A New Scientific Paradigm may be Needed to Finally Develop an HIV Vaccine.
AB  - The bulk of current HIV vaccine research is conducted within the infectious
      disease paradigm that has been very successful in developing vaccines against
      many other viral diseases. Different HIV vaccine concepts, based on the induction
      of neutralizing antibodies and/or cell mediated immunity, have been developed and
      clinically tested over the last 30 years, resulting in a few small successes and
      many disappointments. As new scientific knowledge is obtained, HIV vaccine
      concepts are constantly modified with the hope that the newly introduced tweaks
      (or paradigm drifts) will provide the solution to one of the most difficult
      challenges that modern biomedical research is confronting. Efficacy trials have
      been critical in guiding HIV vaccine development. However, from the five phase
      III efficacy trials conducted to date, only one (RV144) resulted in modest
      efficacy. The results from RV144 were surprising in many ways, including the
      identified putative correlates of protection (or risk), which did not include
      neutralizing antibodies or cytotoxic T-cells. The solution to the HIV vaccine
      challenge may very well come from approaches based on the current paradigm.
      However, at the same time, out-of-the-paradigm ideas should be systematically
      explored to complement the current efforts. New mechanisms are needed to identify
      and support the innovative research that will hopefully accelerate the
      development of an urgently needed HIV vaccine. 

PMID- 25852691
TI  - 4-methylumbelliferone treatment and hyaluronan inhibition as a therapeutic
      strategy in inflammation, autoimmunity, and cancer.
AB  - Hyaluronan (HA) is a prominent component of the extracellular matrix at many
      sites of chronic inflammation, including type 1 diabetes (T1D), multiple
      sclerosis, and numerous malignancies. Recent publications have demonstrated that
      when HA synthesis is inhibited using 4-methylumbelliferone (4-MU), beneficial
      effects are observed in several animal models of these diseases. Notably, 4-MU is
      an already approved drug in Europe and Asia called "hymecromone" where it is used
      to treat biliary spasm. However, there is uncertainty regarding how 4-MU
      treatment provides benefit in these animal models and the potential long-term
      consequences of HA inhibition. Here, we review what is known about how HA
      contributes to immune dysregulation and tumor progression. Then, we review what
      is known about 4-MU and hymecromone in terms of mechanism of action,
      pharmacokinetics, and safety. Finally, we review recent studies detailing the use
      of 4-MU to treat animal models of cancer and autoimmunity. 

PMID- 25852693
TI  - Liver-Stage Specific Response among Endemic Populations: Diet and Immunity.
AB  - Developing effective anti-malarial vaccine has been a challenge for long. Various
      factors including complex life cycle of parasite and lack of knowledge of stage
      specific critical antigens are some of the reasons. Moreover, inadequate
      understanding of the immune responses vis-a-vis sterile protection induced
      naturally by Plasmodia infection has further compounded the problem. It has been
      shown that people living in endemic areas take years to develop protective
      immunity to blood stage infection. But hardly anyone believes that immunity to
      liver-stage infection could be developed. Various experimental model studies
      using attenuated parasite suggest that liver-stage immunity might exist among
      endemic populations. This could be induced because of the attenuation of parasite
      in liver by various compounds present in the diet of endemic populations. 

PMID- 25852694
TI  - A Diverse Repertoire of Human Immunoglobulin Variable Genes in a Chicken B Cell
      Line is Generated by Both Gene Conversion and Somatic Hypermutation.
AB  - Chicken immune responses to human proteins are often more robust than rodent
      responses because of the phylogenetic relationship between the different species.
      For discovery of a diverse panel of unique therapeutic antibody candidates,
      chickens therefore represent an attractive host for human-derived targets. Recent
      advances in monoclonal antibody technology, specifically new methods for the
      molecular cloning of antibody genes directly from primary B cells, has ushered in
      a new era of generating monoclonal antibodies from non-traditional host animals
      that were previously inaccessible through hybridoma technology. However, such
      monoclonals still require post-discovery humanization in order to be developed as
      therapeutics. To obviate the need for humanization, a modified strain of chickens
      could be engineered to express a human-sequence immunoglobulin variable region
      repertoire. Here, human variable genes introduced into the chicken immunoglobulin
      loci through gene targeting were evaluated for their ability to be recognized and
      diversified by the native chicken recombination machinery that is present in the
      B-lineage cell line DT40. After expansion in culture the DT40 population
      accumulated genetic mutants that were detected via deep sequencing. Bioinformatic
      analysis revealed that the human targeted constructs are performing as expected
      in the cell culture system, and provide a measure of confidence that they will be
      functional in transgenic animals. 

PMID- 25852695
TI  - The known unknowns of the human dendritic cell network.
AB  - Dendritic cells (DCs) initiate and orient immune responses and comprise several
      subsets that display distinct phenotypes and properties. Most of our knowledge of
      DC subsets biology is based on mouse studies. In the past few years, the
      alignment of the human DC network with the mouse DC network has been the focus of
      much attention. Although comparative phenotypic and transcriptomic analysis have
      shown a high level of homology between mouse and human DC subsets, significant
      differences in phenotype and function have also been evidenced. Here, we review
      recent advances in our understanding of the human DC network and discuss some
      remaining gaps and future challenges of the human DC field. 

PMID- 25852696
TI  - Induction of Protective Immune Responses Against Schistosomiasis haematobium in
      Hamsters and Mice Using Cysteine Peptidase-Based Vaccine.
AB  - One of the major lessons we learned from the radiation-attenuated cercariae
      vaccine studies is that protective immunity against schistosomiasis is dependent
      on the induction of T helper (Th)1-/Th2-related immune responses. Since most
      schistosome larval and adult-worm-derived molecules used for vaccination
      uniformly induce a polarized Th1 response, it was essential to include a type 2
      immune response-inducing molecule, such as cysteine peptidases, in the vaccine
      formula. Here, we demonstrate that a single subcutaneous injection of Syrian
      hamsters with 200 MUg active papain, 1 h before percutaneous exposure to 150
      cercariae of Schistosoma haematobium, led to highly significant (P < 0.005)
      reduction of >50% in worm burden and worm egg counts in intestine. Immunization
      of hamsters with 20 MUg recombinant glyceraldehyde 3-phosphate dehydrogenase
      (rSG3PDH) and 20 MUg 2-cys peroxiredoxin-derived peptide in a multiple antigen
      peptide construct (PRX MAP) together with papain (20 MUg/hamster), as adjuvant
      led to considerable (64%) protection against challenge S. haematobium infection,
      similar to the levels reported with irradiated cercariae. Cysteine peptidases
      based vaccination was also effective in protecting outbred mice against a
      percutaneous challenge infection with S. haematobium cercariae. In two
      experiments, a mixture of Schistosoma mansoni cathepsin B1 (SmCB1) and Fasciola
      hepatica cathepsin L1 (FhCL1) led to highly significant (P < 0.005) reduction of
      70% in challenge S. haematobium worm burden and 60% reduction in liver egg
      counts. Mice vaccinated with SmCB1/FhCL1/rSG3PDH mixture and challenged with S.
      haematobium cercariae 3 weeks after the second immunization displayed highly
      significant (P < 0.005) reduction of 72% in challenge worm burden and no eggs in
      liver of 8-10 mice/group, as compared to unimmunized mice, associated with
      production of a mixture of type 1- and type 2-related cytokines and antibody
      responses. 

PMID- 25852697
TI  - Behcet's Disease: Do Natural Killer Cells Play a Significant Role?
AB  - Behcet's disease (BD) is a complex inflammatory disease, of unknown etiology.
      While disease pathogenesis remains unclear, a strong relationship between BD and
      HLA-B*51 has been established over the last 30 years. A number of theories exist
      regarding the cause of BD; however, few are able to account for the increased
      rates of HLA-B*51 positive individuals, particularly around the Mediterranean
      basin and Middle-East where the prevalence is highest. This review outlines
      current immunogenetic data on BD and the immunoregulatory role natural killer
      cells may play. It also describes the interaction of the killer immunoglobulin
      like receptor - KIR3DL1 with its ligand Bw4, which is found on HLA-B51. Finally,
      CD94/NKG2D, MICA, and ERAP are outlined with regard to their potential roles in
      BD. 

PMID- 25852699
TI  - Introgression of a rare haplotype from Southeastern Africa to breed California
      blackeyes with larger seeds.
AB  - Seed size distinguishes most crops from their wild relatives and is an important
      quality trait for the grain legume cowpea. In order to breed cowpea varieties
      with larger seeds we introgressed a rare haplotype associated with large seeds at
      the Css-1 locus from an African buff seed type cultivar, IT82E-18 (18.5 g/100
      seeds), into a blackeye seed type cultivar, CB27 (22 g/100 seed). Four
      recombinant inbred lines derived from these two parents were chosen for marker
      assisted breeding based on SNP genotyping with a goal of stacking large seed
      haplotypes into a CB27 background. Foreground and background selection were
      performed during two cycles of backcrossing based on genome-wide SNP markers. The
      average seed size of introgression lines homozygous for haplotypes associated
      with large seeds was 28.7g/100 seed and 24.8 g/100 seed for cycles 1 and 2,
      respectively. One cycle 1 introgression line with desirable seed quality was
      selfed for two generations to make families with very large seeds (28-35 g/100
      seeds). Field-based performance trials helped identify breeding lines that not
      only have large seeds but are also desirable in terms of yield, maturity, and
      plant architecture when compared to industry standards. A principal component
      analysis was used to explore the relationships between the parents relative to a
      core set of landraces and improved varieties based on high-density SNP data. The
      geographic distribution of haplotypes at the Css-1 locus suggest the haplotype
      associated with large seeds is unique to accessions collected from Southeastern
      Africa. Therefore this quantitative trait locus has a strong potential to develop
      larger seeded varieties for other growing regions which is demonstrated in this
      work using a California pedigree. 

PMID- 25852698
TI  - Transcriptomic profiling of linolenic acid-responsive genes in ROS signaling from
      RNA-seq data in Arabidopsis.
AB  - Linolenic acid (Ln) released from chloroplast membrane galactolipids is a
      precursor of the phytohormone jasmonic acid (JA). The involvement of this hormone
      in different plant biological processes, such as responses to biotic stress
      conditions, has been extensively studied. However, the role of Ln in the
      regulation of gene expression during abiotic stress situations mediated by
      cellular redox changes and/or by oxidative stress processes remains poorly
      understood. An RNA-seq approach has increased our knowledge of the interplay
      among Ln, oxidative stress and ROS signaling that mediates abiotic stress
      conditions. Transcriptome analysis with the aid of RNA-seq in the absence of
      oxidative stress revealed that the incubation of Arabidopsis thaliana cell
      suspension cultures (ACSC) with Ln resulted in the modulation of 7525 genes, of
      which 3034 genes had a 2-fold-change, being 533 up- and 2501 down-regulated
      genes, respectively. Thus, RNA-seq data analysis showed that an important set of
      these genes were associated with the jasmonic acid biosynthetic pathway including
      lypoxygenases (LOXs) and Allene oxide cyclases (AOCs). In addition, several
      transcription factor families involved in the response to biotic stress
      conditions (pathogen attacks or herbivore feeding), such as WRKY, JAZ, MYC, and
      LRR were also modified in response to Ln. However, this study also shows that Ln
      has the capacity to modulate the expression of genes involved in the response to
      abiotic stress conditions, particularly those mediated by ROS signaling. In this
      regard, we were able to identify new targets such as galactinol synthase 1
      (GOLS1), methionine sulfoxide reductase (MSR) and alkenal reductase in ACSC. It
      is therefore possible to suggest that, in the absence of any oxidative stress, Ln
      is capable of modulating new sets of genes involved in the signaling mechanism
      mediated by additional abiotic stresses (salinity, UV and high light intensity)
      and especially in stresses mediated by ROS. 

PMID- 25852700
TI  - Production of genetically and developmentally modified seaweeds: exploiting the
      potential of artificial selection techniques.
AB  - Plant feedstock with specific, modified developmental features has been a quest
      for centuries. Since the development and spread of agriculture, there has been a
      desire for plants producing disproportionate-or more abundant and more
      nutritional-biomass that meet human needs better than their native counterparts.
      Seaweed aquaculture, targeted for human consumption and the production of various
      raw materials, is a rapidly expanding field and its stakeholders have increasing
      vested interest for cost-effective and lucrative seaweed cultivation processes.
      Thus, scientific research on seaweed development is particularly timely: the
      potential for expansion of seaweed cultivation depends on the sector's capacity
      to produce seaweeds with modified morphological features (e.g., thicker blades),
      higher growth rates or delayed (or even no) fertility. Here, we review the
      various technical approaches used to modify development in macroalgae, which have
      attracted little attention from developmental biologists to date. Because seaweed
      (or marine macroalgae) anatomy is much less complex than that of land plants and
      because seaweeds belong to three different eukaryotic phyla, the mechanisms
      controlling their morphogenesis are key to understanding their development. Here,
      we present efficient sources of developmentally and genetically modified seaweeds
      somatic variants, artificial hybrids and mutants-as well as the future potential
      of these techniques. 

PMID- 25852701
TI  - Proteome readjustments in the apoplastic space of Arabidopsis thaliana ggt1
      mutant leaves exposed to UV-B radiation.
AB  - Ultraviolet-B radiation acts as an environmental stimulus, but in high doses it
      has detrimental effects on plant metabolism. Plasma membranes represent a major
      target for Reactive Oxygen Species (ROS) generated by this harmful radiation.
      Oxidative reactions occurring in the apoplastic space are counteracted by
      antioxidative systems mainly involving ascorbate and, to some extent,
      glutathione. The occurrence of the latter and its exact role in the extracellular
      space are not well documented, however. In Arabidopsis thaliana, the gamma
      glutamyl transferase isoform (GGT1) bound to the cell wall takes part in the so
      called gamma-glutamyl cycle for extracellular glutathione degradation and
      recovery, and may be implicated in redox sensing and balance. In this work,
      oxidative conditions were imposed with Ultraviolet-B radiation (UV-B) and studied
      in redox altered ggt1 mutants. The response of ggt1 knockout Arabidopsis leaves
      to UV-B radiation was assessed by investigating changes in extracellular
      glutathione and ascorbate content and their redox state, and in apoplastic
      protein composition. Our results show that, on UV-B exposure, soluble
      antioxidants respond to the oxidative conditions in both genotypes.
      Rearrangements occur in their apoplastic protein composition, suggesting an
      involvement of Hydrogen Peroxide (H2O2), which may ultimately act as a signal.
      Other important changes relating to hormonal effects, cell wall remodeling, and
      redox activities are discussed. We argue that oxidative stress conditions imposed
      by UV-B and disruption of the gamma-glutamyl cycle result in similar stress
      induced responses, to some degree at least. Data are available via
      ProteomeXchange with identifier PXD001807. 

PMID- 25852702
TI  - Stable heterologous expression of biologically active terpenoids in green plant
      cells.
AB  - Plants biosynthesize a great diversity of biologically active small molecules of
      interest for fragrances, flavors, and pharmaceuticals. Among specialized
      metabolites, terpenoids represent the greatest molecular diversity. Many
      terpenoids are very complex, and total chemical synthesis often requires many
      steps and difficult chemical reactions, resulting in a low final yield or
      incorrect stereochemistry. Several drug candidates with terpene skeletons are
      difficult to obtain by chemical synthesis due to their large number of chiral
      centers. Thus, biological production remains the preferred method for industrial
      production for many of these compounds. However, because these chemicals are
      often found in low abundance in the native plant, or are produced in plants which
      are difficult to cultivate, there is great interest in engineering increased
      production or expression of the biosynthetic pathways in heterologous hosts.
      Although there are many examples of successful engineering of microbes such as
      yeast or bacteria to produce these compounds, this often requires extensive
      changes to the host organism's metabolism. Optimization of plant gene expression,
      post-translational protein modifications, subcellular localization, and other
      factors often present challenges. To address the future demand for natural
      products used as drugs, new platforms are being established that are better
      suited for heterologous production of plant metabolites. Specifically, direct
      metabolic engineering of plants can provide effective heterologous expression for
      production of valuable plant-derived natural products. In this review, our
      primary focus is on small terpenoids and we discuss the benefits of plant
      expression platforms and provide several successful examples of stable production
      of small terpenoids in plants. 

PMID- 25852703
TI  - Biofortification and phytoremediation of selenium in China.
AB  - Selenium (Se) is an essential trace element for humans and animals but at high
      concentrations, Se becomes toxic to organisms due to Se replacing sulfur in
      proteins. Selenium biofortification is an agricultural process that increases the
      accumulation of Se in crops, through plant breeding, genetic engineering, or use
      of Se fertilizers. Selenium phytoremediation is a green biotechnology to clean up
      Se-contaminated environments, primarily through phytoextraction and
      phytovolatilization. By integrating Se phytoremediation and biofortification
      technologies, Se-enriched plant materials harvested from Se phytoremediation can
      be used as Se-enriched green manures or other supplementary sources of Se for
      producing Se-biofortified agricultural products. Earlier studies primarily aimed
      at enhancing efficacy of phytoremediation and biofortification of Se based on
      natural variation in progenitor or identification of unique plant species. In
      this review, we discuss promising approaches to improve biofortification and
      phytoremediation of Se using knowledge acquired from model crops. We also
      explored the feasibility of applying biotechnologies such as inoculation of
      microbial strains for improving the efficiency of biofortification and
      phytoremediation of Se. The key research and practical challenges that remain in
      improving biofortification and phytoremediation of Se have been highlighted, and
      the future development and uses of Se-biofortified agricultural products in China
      has also been discussed. 

PMID- 25852704
TI  - Cottonseed protein, oil, and mineral status in near-isogenic Gossypium hirsutum
      cotton lines expressing fuzzy/linted and fuzzless/linted seed phenotypes under
      field conditions.
AB  - Cotton is an important crop in the world and is a major source of oil for human
      consumption and cotton meal for livestock. Cottonseed nutrition (seed
      composition: protein, oil, and minerals) determines the quality of seeds.
      Therefore, maintaining optimum levels of cottonseed nutrition is critical.
      Physiological and genetic mechanisms controlling the levels of these constituents
      in cottonseed are still largely unknown. Our previous research conducted under
      greenhouse conditions showed that seed and leaf nutrition differed between
      fuzzless and fuzzy seed isolines. Therefore, the objective of this research was
      to investigate the seed fuzz phenotype (trait) effects on seed protein, oil, N,
      C, S, and minerals in five sets of near-isogenic mutant cotton lines for seed
      fuzz in a 2-year experiment under field condition to evaluate the stability of
      the effect of the trait on seed nutrition. The isolines (genotypes) in each set
      differ for the seed fuzz trait (fuzzless/linted seed line, N lines, and
      fuzzy/linted seed line, F lines). Results showed that seed protein was higher in
      the fuzzy genotype in all sets, but seed oil was higher in fuzzless genotype in
      all sets. The concentrations of seed Ca and C were higher in all fuzzless
      genotypes, but N, S, B, Fe, and Zn were higher in most of the fuzzy genotypes.
      Generally, minerals were higher in leaves of F lines, suggesting the
      translocation of minerals from leaves to seeds was limited. The research
      demonstrated that fiber development could be involved in cottonseed composition.
      This may be due to the involvement of fiber development in carbon and nitrogen
      metabolism, and the mobility of nutrients from leaves (source) to seed (sink).
      This information is beneficial to breeders to consider fuzzless cottonseed for
      potential protein and oil use and select for higher oil or higher protein
      content, and to physiologists to further understand the mobility of minerals to
      increase the quality of cottonseed nutrition for food and feed. 

PMID- 25852705
TI  - Understanding litter decomposition in semiarid ecosystems: linking leaf traits,
      UV exposure and rainfall variability.
AB  - Differences in litter quality, microbial activity or abiotic conditions cannot
      fully account for the variability in decomposition rates observed in semiarid
      ecosystems. Here we tested the role of variation in litter quality, water supply,
      and UV radiation as drivers of litter decomposition in arid lands. And show that
      carry-over effects of litter photodegradation during dry periods can regulate
      decomposition during subsequent wet periods. We present data from a two-phase
      experiment, where we first exposed litter from a drought-deciduous and an
      evergreen shrub to natural UV levels during five, rainless summer months and,
      subsequently, in the laboratory, we assessed the carry-over effects of
      photodegradation on biomass loss under different irrigation treatments
      representing the observed range of local rainfall variation among years (15-240
      mm). Photodegradation of litter in the field produced average carbon losses of
      12%, but deciduous Proustia pungens lost >25%, while evergreen Porlieria
      chilensis less than 5%. Natural exposure to UV significantly reduced carbon-to
      nitrogen and lignin:N ratios in Proustia litter but not in Porlieria. During the
      subsequent wet phase, remaining litter biomass was lower in Proustia than in
      Porlieria. Indeed UV exposure increased litter decomposition of Proustia under
      low and medium rainfall treatments, whereas no carry-over effects were detected
      under high rainfall treatment. Consequently, for deciduous Proustia carry-over
      effects of UV exposure were negligible under high irrigation. Litter
      decomposition of the evergreen Porlieria depended solely on levels of rainfall
      that promote microbial decomposers. Our two-phase experiment revealed that both
      the carry-over effects of photodegradation and litter quality, modulated by inter
      annual variability in rainfall, can explain the marked differences in
      decomposition rates and the frequent decoupling between rainfall and litter
      decomposition observed in semiarid ecosystems. 

PMID- 25852706
TI  - Uncovering the genetic architecture of Colletotrichum lindemuthianum resistance
      through QTL mapping and epistatic interaction analysis in common bean.
AB  - Colletotrichum lindemuthianum is a hemibiotrophic fungal pathogen that causes
      anthracnose disease in common bean. Despite the genetics of anthracnose
      resistance has been studied for a long time, few quantitative trait loci (QTLs)
      studies have been conducted on this species. The present work examines the
      genetic basis of quantitative resistance to races 23 and 1545 of C.
      lindemuthianum in different organs (stem, leaf and petiole). A population of 185
      recombinant inbred lines (RIL) derived from the cross PMB0225 * PHA1037 was
      evaluated for anthracnose resistance under natural and artificial photoperiod
      growth conditions. Using multi-environment QTL mapping approach, 10 and 16 main
      effect QTLs were identified for resistance to anthracnose races 23 and 1545,
      respectively. The homologous genomic regions corresponding to 17 of the 26 main
      effect QTLs detected were positive for the presence of resistance-associated gene
      cluster encoding nucleotide-binding and leucine-rich repeat (NL) proteins. Among
      them, it is worth noting that the main effect QTLs detected on linkage group 05
      for resistance to race 1545 in stem, petiole and leaf were located within a 1.2
      Mb region. The NL gene Phvul.005G117900 is located in this region, which can be
      considered an important candidate gene for the non-organ-specific QTL identified
      here. Furthermore, a total of 39 epistatic QTL (E-QTLs) (21 for resistance to
      race 23 and 18 for resistance to race 1545) involved in 20 epistatic interactions
      (eleven and nine interactions for resistance to races 23 and 1545, respectively)
      were identified. None of the main and epistatic QTLs detected displayed
      significant environment interaction effects. The present research provides
      essential information not only for the better understanding of the plant-pathogen
      interaction but also for the application of genomic assisted breeding for
      anthracnose resistance improvement in common bean through application of marker
      assisted selection (MAS). 

PMID- 25852707
TI  - Protein profile of Beta vulgaris leaf apoplastic fluid and changes induced by Fe
      deficiency and Fe resupply.
AB  - The fluid collected by direct leaf centrifugation has been used to study the
      proteome of the sugar beet apoplastic fluid as well as the changes induced by Fe
      deficiency and Fe resupply to Fe-deficient plants in the protein profile. Plants
      were grown in Fe-sufficient and Fe-deficient conditions, and Fe resupply was
      carried out with 45 MUM Fe(III)-EDTA for 24 h. Protein extracts of leaf
      apoplastic fluid were analyzed by two-dimensional isoelectric focusing-SDS-PAGE
      electrophoresis. Gel image analysis revealed 203 consistent spots, and proteins
      in 81% of them (164) were identified by nLC-MS/MS using a custom made reference
      repository of beet protein sequences. When redundant UniProt entries were
      deleted, a non-redundant leaf apoplastic proteome consisting of 109 proteins was
      obtained. TargetP and SecretomeP algorithms predicted that 63% of them were
      secretory proteins. Functional classification of the non-redundant proteins
      indicated that stress and defense, protein metabolism, cell wall and C metabolism
      accounted for approximately 75% of the identified proteome. The effects of Fe
      deficiency on the leaf apoplast proteome were limited, with only five spots
      (2.5%) changing in relative abundance, thus suggesting that protein homeostasis
      in the leaf apoplast fluid is well-maintained upon Fe shortage. The
      identification of three chitinase isoforms among proteins increasing in relative
      abundance with Fe-deficiency suggests that one of the few effects of Fe
      deficiency in the leaf apoplast proteome includes cell wall modifications. Iron
      resupply to Fe deficient plants changed the relative abundance of 16 spots when
      compared to either Fe-sufficient or Fe-deficient samples. Proteins identified in
      these spots can be broadly classified as those responding to Fe-resupply, which
      included defense and cell wall related proteins, and non-responsive, which are
      mainly protein metabolism related proteins and whose changes in relative
      abundance followed the same trend as with Fe-deficiency. 

PMID- 25852709
TI  - Auxin metabolism rates and implications for plant development.
AB  - Studies of auxin metabolism rarely express their results as a metabolic rate,
      although the data obtained would often permit such a calculation to be made. We
      analyze data from 31 previously published papers to quantify the rates of auxin
      biosynthesis, conjugation, conjugate hydrolysis, and catabolism in seed plants.
      Most metabolic pathways have rates in the range 10 nM/h-1 MUM/h, with the
      exception of auxin conjugation, which has rates as high as ~100 MUM/h. The high
      rates of conjugation suggest that auxin metabolic sinks may be very small,
      perhaps as small as a single cell. By contrast, the relatively low rate of auxin
      biosynthesis requires plants to conserve and recycle auxin during long-distance
      transport. The consequences for plant development are discussed. 

PMID- 25852708
TI  - An update on polygalacturonase-inhibiting protein (PGIP), a leucine-rich repeat
      protein that protects crop plants against pathogens.
AB  - Polygalacturonase inhibiting proteins (PGIPs) are cell wall proteins that inhibit
      the pectin-depolymerizing activity of polygalacturonases secreted by microbial
      pathogens and insects. These ubiquitous inhibitors have a leucine-rich repeat
      structure that is strongly conserved in monocot and dicot plants. Previous
      reviews have summarized the importance of PGIP in plant defense and the
      structural basis of PG-PGIP interaction; here we update the current knowledge
      about PGIPs with the recent findings on the composition and evolution of pgip
      gene families, with a special emphasis on legume and cereal crops. We also update
      the information about the inhibition properties of single pgip gene products
      against microbial PGs and the results, including field tests, showing the
      capacity of PGIP to protect crop plants against fungal, oomycetes and bacterial
      pathogens. 

PMID- 25852710
TI  - Genetic diversity and genomic resources available for the small millet crops to
      accelerate a New Green Revolution.
AB  - Small millets are nutrient-rich food sources traditionally grown and consumed by
      subsistence farmers in Asia and Africa. They include finger millet (Eleusine
      coracana), foxtail millet (Setaria italica), kodo millet (Paspalum
      scrobiculatum), proso millet (Panicum miliaceum), barnyard millet (Echinochloa
      spp.), and little millet (Panicum sumatrense). Local farmers value the small
      millets for their nutritional and health benefits, tolerance to extreme stress
      including drought, and ability to grow under low nutrient input conditions, ideal
      in an era of climate change and steadily depleting natural resources. Little
      scientific attention has been paid to these crops, hence they have been termed
      "orphan cereals." Despite this challenge, an advantageous quality of the small
      millets is that they continue to be grown in remote regions of the world which
      has preserved their biodiversity, providing breeders with unique alleles for crop
      improvement. The purpose of this review, first, is to highlight the diverse
      traits of each small millet species that are valued by farmers and consumers
      which hold potential for selection, improvement or mechanistic study. For each
      species, the germplasm, genetic and genomic resources available will then be
      described as potential tools to exploit this biodiversity. The review will
      conclude with noting current trends and gaps in the literature and make
      recommendations on how to better preserve and utilize diversity within these
      species to accelerate a New Green Revolution for subsistence farmers in Asia and
      Africa. 

PMID- 25852711
TI  - Antioxidant response and related gene expression in aged oat seed.
AB  - To evaluate deterioration of oat seeds during storage, we analyzed oxygen
      radicals, antioxidant enzyme activity, proline content, and gene transcript
      levels in oat seeds with different moisture contents (MCs; 4, 16, and 28% w/w)
      during storage for 0, 6, and 12 months (CK, LT-6, and LT-12 treatments,
      respectively) at 4 degrees C. The germination percentage decreased significantly
      with higher seed MCs and longer storage duration. The concentrations of
      superoxide radical and hydrogen peroxide increased with seed MC increasing. The
      activities of catalase (CAT), ascorbate peroxidase (APX), and superoxide
      dismutase (SOD) may have had a complementary or interacting role to scavenge
      reactive oxygen species. As the storage duration extended, the proline content
      decreased in seeds with 4 and 16% MC and increased in 28%. These findings suggest
      that proline played the main role in adaptation to oxidative stress in seeds with
      higher MC (28%), while antioxidant enzymes played the main role in seeds with
      lower MCs (4%, 16%). In the gene transcript analyses, SOD1 transcript levels were
      not consistent with total SOD activity. The transcript levels of APX1 and CAT1
      showed similar trends to those of APX and CAT activity. The transcript levels of
      P5CS1, which encodes a proline biosynthetic enzyme, increased with seed MC
      increasing in CK. Compared with changing of proline content in seeds stored 12
      months, PDH1 transcript levels showed the opposite trend and maintained the lower
      levels in seeds of 16 and 28% MCs. The transcript level of P5CS1 was
      significantly affected by MC, and PDH1 could improve stress resistance for seed
      aging and maintain seed vigor during long-term storage. 

PMID- 25852712
TI  - Arabidopsis histone demethylases LDL1 and LDL2 control primary seed dormancy by
      regulating DELAY OF GERMINATION 1 and ABA signaling-related genes.
AB  - Seed dormancy controls germination and plays a critical role in regulating the
      beginning of the life cycle of plants. Seed dormancy is established and
      maintained during seed maturation and is gradually broken during dry storage
      (after-ripening). The plant hormone abscisic acid (ABA) and DELAY OF GERMINATION1
      (DOG1) protein are essential regulators of seed dormancy. Recent studies revealed
      that chromatin modifications are also involved in the transcription regulation of
      seed dormancy. Here, we showed that two Arabidopsis histone demethylases,
      LYSINESPECIFIC DEMETHYLASE LIKE 1 and 2 (LDL1 and LDL2) act redundantly in
      repressing of seed dormancy. LDL1 and LDL2 are highly expressed in the early
      silique developing stage. The ldl1 ldl2 double mutant displays increased seed
      dormancy, whereas overexpression of LDL1 or LDL2 in Arabidopsis causes reduced
      dormancy. Furthermore, we showed that LDL1 and LDL2 repress the expression of
      seed dormancy-related genes, including DOG1, ABA2 and ABI3 during seed dormancy
      establishment. Furthermore, genetic analysis revealed that the repression of seed
      dormancy by LDL1 and LDL2 requires DOG1, ABA2, and ABI3. Taken together, our
      findings revealed that LDL1 and LDL2 play an essential role in seed dormancy. 

PMID- 25852713
TI  - The use of the ph1b mutant to induce recombination between the chromosomes of
      wheat and barley.
AB  - Intensive breeding has led to a narrowing in the genetic base of our major crops.
      In wheat, access to the extensive gene pool residing in its many and varied
      relatives (some cultivated, others wild) is hampered by the block on
      recombination imposed by the Ph1 (Pairing homoeologous 1) gene. Here, the ph1b
      mutant has been exploited to induced allosyndesis between wheat chromosomes and
      those of both Hordeum vulgare (cultivated barley) and H. chilense (a wild
      barley). A number of single chromosome Hordeum sp. substitution and addition
      lines in wheat were crossed and backcrossed to the ph1b mutant to produce plants
      in which pairing between the wheat and the non-wheat chromosomes was not
      suppressed by the presence of Ph1. Genomic in situ hybridization was applied to
      almost 500 BC1F2 progeny as a screen for allosyndetic recombinants. Chromosome
      rearrangements were detected affecting H. chilense chromosomes 4H (ch) , 5H (ch)
      , 6H (ch) , and 7H (ch) and H. vulgare chromosomes 4H (v) , 6H (v) , and 7H (v) .
      Two of these were clearly the product of a recombination event involving
      chromosome 4H (ch) and a wheat chromosome. 

PMID- 25852714
TI  - Dynamics of long-distance signaling via plant vascular tissues.
AB  - Plant vascular systems are constructed by specific cell wall modifications
      through which cells are highly specialized to make conduits for water and
      nutrients. Xylem vessels are formed by thickened cell walls that remain after
      programmed cell death, and serve as water conduits from the root to the shoot. In
      contrast, phloem tissues consist of a complex of living cells, including sieve
      tube elements and their neighboring companion cells, and translocate
      photosynthetic assimilates from mature leaves to developing young tissues.
      Intensive studies on the content of vascular flow fluids have unveiled that plant
      vascular tissues transport various types of gene product, and the transport of
      some provides the molecular basis for the long-distance communications. Analysis
      of xylem sap has demonstrated the presence of proteins in the xylem transpiration
      stream. Recent studies have revealed that CLE and CEP peptides secreted in the
      roots are transported to above ground via the xylem in response to plant-microbe
      interaction and soil nitrogen starvation, respectively. Their leucine-rich repeat
      transmembrane receptors localized in the shoot phloem are required for relaying
      the signal from the shoot to the root. These findings well-fit to the current
      scenario of root-to-shoot-to-root feedback signaling, where peptide transport
      achieves the root-to-shoot signaling, the first half of the signaling process.
      Meanwhile, it is now well-evidenced that proteins and a range of RNAs are
      transported via the phloem translocation system, and some of those can exert
      their physiological functions at their destinations, including roots. Thus, plant
      vascular systems may serve not only as conduits for the translocation of
      essential substances but also as long-distance communication pathways that allow
      plants to adapt to changes in internal and external environments at the whole
      plant level. 

PMID- 25852716
TI  - Metabolic engineering of medium-chain fatty acid biosynthesis in Nicotiana
      benthamiana plant leaf lipids.
AB  - Various research groups are investigating the production of oil in non-seed
      biomass such as leaves. Recently, high levels of oil accumulation have been
      achieved in plant biomass using a combination of biotechnological approaches
      which also resulted in significant changes to the fatty acid composition of the
      leaf oil. In this study, we were interested to determine whether medium-chain
      fatty acids (MCFA) could be accumulated in leaf oil. MCFA are an ideal feedstock
      for biodiesel and a range of oleochemical products including lubricants,
      coatings, and detergents. In this study, we explore the synthesis, accumulation,
      and glycerolipid head-group distribution of MCFA in leaves of Nicotiana
      benthamiana after transient transgenic expression of C12:0-, C14:0-, and C16:0
      ACP thioesterase genes. We demonstrate that the production of these MCFA in leaf
      is increased by the co-expression of the WRINKLED1 (WRI1) transcription factor,
      with the lysophosphatidic acid acyltransferase (LPAAT) from Cocos nucifera being
      required for the assembly of tri-MCFA TAG species. We also demonstrate that the
      newly-produced MCFA are incorporated into the triacylglycerol of leaves in which
      WRI1 + diacylglycerol acyltransferase1 (DGAT1) genes are co-expressed for
      increased oil accumulation. 

PMID- 25852717
TI  - Sensitivity of cold acclimation to elevated autumn temperature in field-grown
      Pinus strobus seedlings.
AB  - Climate change will increase autumn air temperature, while photoperiod decrease
      will remain unaffected. We assessed the effect of increased autumn air
      temperature on timing and development of cold acclimation and freezing resistance
      in Eastern white pine (EWP, Pinus strobus) under field conditions. For this
      purpose we simulated projected warmer temperatures for southern Ontario in a
      Temperature Free-Air-Controlled Enhancement (T-FACE) experiment and exposed EWP
      seedlings to ambient (Control) or elevated temperature (ET, +1.5 degrees C/+3
      degrees C during day/night). Photosynthetic gas exchange, chlorophyll
      fluorescence, photoprotective pigments, leaf non-structural carbohydrates (NSC),
      and cold hardiness were assessed over two consecutive autumns. Nighttime
      temperature below 10 degrees C and photoperiod below 12 h initiated
      downregulation of assimilation in both treatments. When temperature further
      decreased to 0 degrees C and photoperiod became shorter than 10 h, downregulation
      of the light reactions and upregulation of photoprotective mechanisms occurred in
      both treatments. While ET seedlings did not delay the timing of the
      downregulation of assimilation, stomatal conductance in ET seedlings was
      decreased by 20-30% between August and early October. In both treatments leaf NSC
      composition changed considerably during autumn but differences between Control
      and ET seedlings were not significant. Similarly, development of freezing
      resistance was induced by exposure to low temperature during autumn, but the
      timing was not delayed in ET seedlings compared to Control seedlings. Our results
      indicate that EWP is most sensitive to temperature changes during October and
      November when downregulation of photosynthesis, enhancement of photoprotection,
      synthesis of cold-associated NSCs and development of freezing resistance occur.
      However, we also conclude that the timing of the development of freezing
      resistance in EWP seedlings is not affected by moderate temperature increases
      used in our field experiments. 

PMID- 25852718
TI  - Transcriptomic insights into antagonistic effects of gibberellin and abscisic
      acid on petal growth in Gerbera hybrida.
AB  - Petal growth is central to floral morphogenesis, but the underlying genetic basis
      of petal growth regulation is yet to be elucidated. In this study, we found that
      the basal region of the ray floret petals of Gerbera hybrida was the most
      sensitive to treatment with the phytohormones gibberellin (GA) and abscisic acid
      (ABA), which regulate cell expansion during petal growth in an antagonistic
      manner. To screen for differentially expressed genes (DEGs) and key regulators
      with potentially important roles in petal growth regulation by GA or/and ABA, the
      RNA-seq technique was employed. Differences in global transcription in petals
      were observed in response to GA and ABA and target genes antagonistically
      regulated by the two hormones were identified. Moreover, we also identified the
      pathways associated with the regulation of petal growth after application of
      either GA or ABA. Genes relating to the antagonistic GA and ABA regulation of
      petal growth showed distinct patterns, with genes encoding transcription factors
      (TFs) being active during the early stage (2 h) of treatment, while genes from
      the "apoptosis" and "cell wall organization" categories were expressed at later
      stages (12 h). In summary, we present the first study of global expression
      patterns of hormone-regulated transcripts in G. hybrida petals; this dataset will
      be instrumental in revealing the genetic networks that govern petal morphogenesis
      and provides a new theoretical basis and novel gene resources for ornamental
      plant breeding. 

PMID- 25852719
TI  - Recent developments in fast spectroscopy for plant mineral analysis.
AB  - Ideal fertilizer management to optimize plant productivity and quality is more
      relevant than ever, as global food demands increase along with the rapidly
      growing world population. At the same time, sub-optimal or excessive use of
      fertilizers leads to severe environmental damage in areas of intensive crop
      production. The approaches of soil and plant mineral analysis are briefly
      compared and discussed here, and the new techniques using fast spectroscopy that
      offer cheap, rapid, and easy-to-use analysis of plant nutritional status are
      reviewed. The majority of these methods use vibrational spectroscopy, such as
      visual-near infrared and to a lesser extent ultraviolet and mid-infrared
      spectroscopy. Advantages of and problems with application of these techniques are
      thoroughly discussed. Spectroscopic techniques considered having major potential
      for plant mineral analysis, such as chlorophyll a fluorescence, X-ray
      fluorescence, and laser-induced breakdown spectroscopy are also described. 

PMID- 25852715
TI  - Osmotin: a plant sentinel and a possible agonist of mammalian adiponectin.
AB  - Osmotin is a stress responsive antifungal protein belonging to the pathogenesis
      related (PR)-5 family that confers tolerance to both biotic and abiotic stresses
      in plants. Protective efforts of osmotin in plants range from high temperature to
      cold and salt to drought. It lyses the plasma membrane of the pathogens. It is
      widely distributed in fruits and vegetables. It is a differentially expressed and
      developmentally regulated protein that protects the cells from osmotic stress and
      invading pathogens as well, by structural or metabolic alterations. During stress
      conditions, osmotin helps in the accumulation of the osmolyte proline, which
      quenches reactive oxygen species and free radicals. Osmotin expression results in
      the accumulation of storage reserves and increases the shelf-life of fruits. It
      binds to a seven-transmembrane-domain receptor-like protein and induces
      programmed cell death in Saccharomyces cerevisiae through RAS2/cAMP signaling
      pathway. Adiponectin, produced in adipose tissues of mammals, is an insulin
      sensitizing hormone. Strangely, osmotin acts like the mammalian hormone
      adiponectin in various in vitro and in vivo models. Adiponectin and osmotin, the
      two receptor binding proteins do not share sequence similarity at the amino acid
      level, but interestingly they have a similar structural and functional
      properties. In experimental mice, adiponectin inhibits endothelial cell
      proliferation and migration, primary tumor growth, and reduces atherosclerosis.
      This retrospective work examines the vital role of osmotin in plant defense and
      as a potential targeted therapeutic drug for humans. 

PMID- 25852721
TI  - Crown traits of coniferous trees and their relation to shade tolerance can differ
      with leaf type: a biophysical demonstration using computed tomography scanning
      data.
AB  - Plant light interception and shade tolerance are intrinsically related in that
      they involve structural, morphological and physiological adaptations to manage
      light capture for photosynthetic utilization, in order to sustain survival,
      development and reproduction. At the scale of small-size trees, crown traits
      related to structural geometry of branching pattern and space occupancy through
      phyllotaxis can be accurately evaluated in 3D, using computed tomography (CT)
      scanning data. We demonstrate this by scrutinizing the crowns of 15 potted
      miniature conifers of different species or varieties, classified in two groups
      based on leaf type (10 needlelike, 5 scalelike); we also test whether mean values
      of crown traits measured from CT scanning data and correlations with a shade
      tolerance index (STI) differ between groups. Seven crown traits, including
      fractal dimensions (FD1: smaller scales, FD2: larger scales) and leaf areas, were
      evaluated for all 15 miniature conifers; an average silhouette-to-total-area
      ratio was also calculated for each of the 10 needlelike-leaf conifers. Between
      group differences in mean values are significant (P < 0.05) for STI, FD1, FD2,
      and the average leaf area displayed (AD). Between-group differences in sign and
      strength of correlations are observed. For example, the correlation between STI
      and FD1 is negative and significant (P < 0.10) for the needlelike-leaf group, but
      is positive and significant (P < 0.05) for the miniature conifers with scalelike
      leaves, which had lower STI and higher FD1 on average in our study; the positive
      correlation between STI and AD is significant (P < 0.05) for the scalelike-leaf
      group, and very moderate for the needlelike-leaf one. A contrasting physical
      attachment of the leaves to branches may explain part of the between-group
      differences. Our findings open new avenues for the understanding of fundamental
      plant growth processes; the information gained could be included in a multi-scale
      approach to tree crown modeling. 

PMID- 25852720
TI  - Salicylic acid and reactive oxygen species interplay in the transcriptional
      control of defense genes expression.
AB  - It is well established that salicylic acid (SA) plays a critical role in the
      transcriptional reprograming that occurs during the plant defense response
      against biotic and abiotic stress. In the course of the defense response, the
      transcription of different sets of defense genes is controlled in a spatio
      temporal manner via SA-mediated mechanisms. Interestingly, different lines of
      evidence indicate that SA interplays with reactive oxygen species (ROS) and
      glutathione (GSH) in stressed plants. In this review we focus on the evidence
      that links SA, ROS, and GSH signals to the transcriptional control of defense
      genes. We discuss how redox modifications of regulators and co-regulators
      involved in SA-mediated transcriptional responses control the temporal patterns
      of gene expression in response to stress. Finally, we examine how these redox
      sensors are coordinated with the dynamics of cellular redox changes occurring in
      the defense response to biotic and abiotic stress. 

PMID- 25852722
TI  - The male germline of angiosperms: repertoire of an inconspicuous but important
      cell lineage.
AB  - The male germline of flowering plants constitutes a specialized lineage of
      diminutive cells initiated by an asymmetric division of the initial microspore
      cell that sequesters the generative cell from the pollen vegetative cell. The
      generative cell subsequently divides to form the two male gametes (non-motile
      sperm cells) that fuse with the two female gametophyte target cells (egg and
      central cells) to form the zygote and endosperm. Although these male gametes can
      be as little as 1/800th of the volume of their female counterpart, they encode a
      highly distinctive and rich transcriptome, translate proteins, and display a
      novel suite of gamete-distinctive control elements that create a unique chromatin
      environment in the male lineage. Sperm-expressed transcripts also include a high
      proportion of transposable element-related sequences that may be targets of non
      coding RNA including miRNA and silencing elements from peripheral cells. The
      number of sperm-encoded transcripts is somewhat fewer than the number present in
      the egg cell, but are remarkably distinct compared to other cell types according
      to principal component and other analyses. The molecular role of the male germ
      lineage cells is just beginning to be understood and appears more complex than
      originally anticipated. 

PMID- 25852724
TI  - Analysis of genetic variation and diversity of Rice stripe virus populations
      through high-throughput sequencing.
AB  - Plant RNA viruses often generate diverse populations in their host plants through
      error-prone replication and recombination. Recent studies on the genetic
      diversity of plant RNA viruses in various host plants have provided valuable
      information about RNA virus evolution and emergence of new diseases caused by RNA
      viruses. We analyzed and compared the genetic diversity of Rice stripe virus
      (RSV) populations in Oryza sativa (a natural host of RSV) and compared it with
      that of the RSV populations generated in an infection of Nicotiana benthamiana,
      an experimental host of RSV, using the high-throughput sequencing technology.
      From infected O. sativa and N. benthamiana plants, a total of 341 and 1675 site
      substitutions were identified in the RSV genome, respectively, and the average
      substitution ratio in these sites was 1.47 and 7.05 %, respectively, indicating
      that the RSV populations from infected N. benthamiana plant are more diverse than
      those from infected O. sativa plant. Our result gives a direct evidence that
      virus might allow higher genetic diversity for host adaptation. 

PMID- 25852723
TI  - Interconnection between flowering time control and activation of systemic
      acquired resistance.
AB  - The ability to avoid or neutralize pathogens is inherent to all higher organisms
      including plants. Plants recognize pathogens through receptors, and mount
      resistance against the intruders, with the help of well-elaborated defense
      arsenal. In response to some localinfections, plants develop systemic acquired
      resistance (SAR), which provides heightened resistance during subsequent
      infections. Infected tissues generate mobile signaling molecules that travel to
      the systemic tissues, where they epigenetically modify expression o a set of
      genes to initiate the manifestation of SAR in distant tissues. Immune responses
      are largely regulated at transcriptional level. Flowering is a developmental
      transition that occurs as a result of the coordinated action of large numbers of
      transcription factors that respond to intrinsic signals and environmental
      conditions. The plant hormone salicylic acid (SA) which is required for SAR
      activation positively regulates flowering. Certain components of chromatin
      remodeling complexes that are recruited for suppression of precocious flowering
      are also involved in suppression of SAR in healthy plants. FLOWERING LOCUS D, a
      putative histone demethylase positively regulates SAR manifestation and flowering
      transition in Arabidopsis. Similarly, incorporation of histone variant H2A.Z in
      nucleosomes mediated by PHOTOPERIOD-INDEPENDENT EARLY FLOWERING 1, an ortholog of
      yeast chromatin remodeling complex SWR1, concomitantly influences SAR and
      flowering time. SUMO conjugation and deconjugation mechanisms also similarly
      affect SAR and flowering in an SA-dependent manner. The evidences suggest a
      common underlying regulatory mechanism for activation of SAR and flowering in
      plants. 

PMID- 25852725
TI  - Lathyrus sativus transcriptome resistance response to Ascochyta lathyri
      investigated by deepSuperSAGE analysis.
AB  - Lathyrus sativus (grass pea) is a temperate grain legume crop with a great
      potential for expansion in dry areas or zones that are becoming more drought
      prone. It is also recognized as a potential source of resistance to several
      important diseases in legumes, such as ascochyta blight. Nevertheless, the lack
      of detailed genomic and/or transcriptomic information hampers further
      exploitation of grass pea resistance-related genes in precision breeding. To
      elucidate the pathways differentially regulated during ascochyta-grass pea
      interaction and to identify resistance candidate genes, we compared the early
      response of the leaf gene expression profile of a resistant L. sativus genotype
      to Ascochyta lathyri infection with a non-inoculated control sample from the same
      genotype employing deepSuperSAGE. This analysis generated 14.387 UniTags of which
      95.7% mapped to a reference grass pea/rust interaction transcriptome. From the
      total mapped UniTags, 738 were significantly differentially expressed between
      control and inoculated leaves. The results indicate that several gene classes
      acting in different phases of the plant/pathogen interaction are involved in the
      L. sativus response to A. lathyri infection. Most notably a clear up-regulation
      of defense-related genes involved in and/or regulated by the ethylene pathway was
      observed. There was also evidence of alterations in cell wall metabolism
      indicated by overexpression of cellulose synthase and lignin biosynthesis genes.
      This first genome-wide overview of the gene expression profile of the L. sativus
      response to ascochyta infection delivered a valuable set of candidate resistance
      genes for future use in precision breeding. 

PMID- 25852726
TI  - The soybean GmDi19-5 interacts with GmLEA3.1 and increases sensitivity of
      transgenic plants to abiotic stresses.
AB  - Drought-induced (Di19) proteins played important roles in plant growth,
      development, and abiotic stress responses. In the present study, a total of seven
      Di19 genes were identified in soybean. Each soybean Di19 gene showed specific
      responses to salt, drought, oxidative, and ABA stresses based on expression
      profiles. With a relatively higher transcript level among Di19 members under four
      stress treatments, GmDi19-5 was selected for detailed analysis. Inhibitor assays
      revealed that ABA inhibitor (Fluridone) or H2O2 inhibitor (DMTU) was involved in
      the drought- or salt-induced transcription of GmDi19-5. The GUS activity driven
      by the GmDi19-5 promoter was induced by salt, PEG, ABA, and MV treatments and
      tended to be accumulated in the vascular bundles and young leaves. A subcellular
      localization assay showed that GmDi19-5 protein localized in the nucleus. Further
      investigation showed that GmDi19-5 protein was involved in the interaction with
      GmLEA3.1. Overexpression of GmDi19-5 increased sensitivity of transgenic
      Arabidopsis plants to salt, drought, oxidative, and ABA stresses and regulated
      expression of several ABA/stress-associated genes. This present investigation
      showed that GmDi19-5 functioned as a negative factor under abiotic stresses and
      was involved in ABA and SOS signaling pathway by altering transcription of stress
      associated genes. 

PMID- 25852727
TI  - Fructan and hormone connections.

PMID- 25852728
TI  - Copper-induced activation of TRP channels promotes extracellular calcium entry,
      activation of CaMs and CDPKs, copper entry and membrane depolarization in Ulva
      compressa.
AB  - In order to identify channels involved in membrane depolarization, Ulva compressa
      was incubated with agonists of TRP channels C5, A1 and V1, and the level of
      intracellular calcium was detected. Agonists of TRPC5, A1 and V1 induced
      increases in intracellular calcium at 4, 9, and 11 min of exposure, respectively,
      and antagonists of TRPC5, A1, and V1 corresponding to SKF-96365 (SKF), HC-030031
      (HC), and capsazepin (CPZ), respectively, inhibited calcium increases indicating
      that functional TRPs exist in U. compressa. In addition, copper excess induced
      increases in intracellular calcium at 4, 9, and 12 min which were inhibited by
      SKF, HC, and CPZ, respectively, indicating that copper activate TRPC5, A1, and V1
      channels. Moreover, copper-induced calcium increases were inhibited by EGTA, a
      non-permeable calcium chelating agent, but not by thapsigargin, an inhibitor of
      endoplasmic reticulum (ER) calcium ATPase, indicating that activation of TRPs
      leads to extracellular calcium entry. Furthermore, copper-induced calcium
      increases were not inhibited by W-7, an inhibitor of CaMs, and staurosporine, an
      inhibitor of CDPKs, indicating that extracellular calcium entry did not require
      activation of CaMs and CDPKs. In addition, copper induced membrane depolarization
      events at 4, 8, and 11 min and these events were inhibited by SKF, HC, CPZ, and
      bathocuproine, a specific copper chelating agent, indicating that copper entry
      through TRP channels leads to membrane depolarization. Moreover, membrane
      depolarization events were inhibited by W-7 and staurosporine, indicating that
      activation of CaMs and CDPKs is required to allow copper entry through TRPs.
      Interestingly, copper-induced calcium increases and depolarization events were
      light-dependent and were inhibited by DCMU, an inhibitor of photosystem II, and
      ATP-gamma-S, a non-hydrolizable analog of ATP, suggesting that ATP derived from
      photosynthesis is required to activate TRPs. Thus, light-dependent copper-induced
      activation TRPC5, A1 and V1 promotes extracellular calcium entry leading to
      activation of CaMs and CDPKs which, in turn, promotes copper entry through TRP
      channels and membrane depolarization. 

PMID- 25852729
TI  - MALDI-TOF MS profiling approach: how much can we get from it?

PMID- 25852730
TI  - MicroRNA399 is involved in multiple nutrient starvation responses in rice.
AB  - The increasing evidences have revealed that microRNAs (miRNAs) play significant
      role in nutrient stress response. Previously, miR399 was documented to be induced
      by phosphorus (P) starvation and involved in regulating P starvation responses.
      To further investigate the function of miR399 in rice (Oryza sativa L.), we
      performed GeneChip analysis with OsmiR399 over-expressing plants. Interestingly,
      our results showed that, besides P starvation responsive genes, the expression of
      a number of genes involved in iron (Fe), potassium (K), sodium (Na), and calcium
      (Ca) absorption was dramatically up-regulated in OsmiR399 over-expressing plants.
      Consistently, the concentrations of Fe, K, Na, and Ca were also increased in
      OsmiR399 over-expressing plants. The expression of OsmiR399 was also up-regulated
      by these nutrient starvations, respectively. Moreover, the loss-of-function of
      LTN1, the down-stream target of OsmiR399, also resulted in the increase of
      multiple metal elements and the up-regulation of the absorption related genes.
      These results indicated that OsmiR399 participates in the regulation of multiple
      nutrient starvation responses, which also gives new view on understanding the
      interaction among different nutrients mediated by miR399. 

PMID- 25852731
TI  - Anosognosia in people with cognitive impairment: association with cognitive
      deficits and behavioral disturbances.
AB  - AIMS: To investigate, in a group of subjects at an early stage of cognitive
      impairment, the relationship between anosognosia and both cognitive and
      behavioral symptoms by exploring the various domains of insight. METHODS: One
      hundred and eight subjects affected by cognitive impairment were consecutively
      enrolled. The level of awareness was evaluated by means of the Clinical Insight
      Rating Scale (CIRS). Psychiatric symptoms were evaluated using the Italian
      version of the Neuropsychiatric Inventory (NPI), whereas memory (memory index,
      MI) and executive (executive index, EI) functions were explored using a battery
      of neuropsychological tests and qualified by means of a single composite
      cognitive index score for each function. RESULTS: A significant positive
      correlation between the total NPI score and global anosognosia score was found.
      Furthermore, both the MI and EI scores were lower in subjects with anosognosia
      than in those without anosognosia (p < 0.001 and p < 0.007, respectively). When
      the single domains of the CIRS were considered, anosognosia of reason of visit
      correlated with the EI score (r = -0.327, p = 0.01) and night-time behavioral
      disturbances (r = 0.225; p = 0.021); anosognosia of cognitive deficit correlated
      with depression (r = -0.193; p = 0.049) and the MI score (r = -0.201; p = 0.040);
      anosognosia of functional deficit correlated with the MI score (r = -0.257; p =
      0.008), delusions (r = 0.232; p = 0.015) and aberrant motor behavior (r = 0.289;
      p = 0.003); anosognosia of disease progression correlated with the MI score (r = 
      0.236; p = 0.015), agitation (r = 0.247; p = 0.011), aberrant motor behavior (r =
      0.351; p = 0.001) and night-time behavioral disturbances (r = 0.216; p = 0.027).
      CONCLUSIONS: Our study suggests that, in the early stage of cognitive impairment,
      anosognosia is associated with both cognitive deficits and behavioral disorders
      according to the specific functional anatomy of the symptoms.

PMID- 25852732
TI  - Effects of pioglitazone or exercise in older adults with mild cognitive
      impairment and insulin resistance: a pilot study.
AB  - AIMS: To examine the effects of pioglitazone or endurance exercise training on
      cognitive function in older adults with mild cognitive impairment (MCI) and
      insulin resistance. METHODS: Seventy-eight adults (mean age +/- SD: 65 +/- 7
      years) with central obesity and MCI were randomized to 6 months of endurance
      exercise, pioglitazone or control. RESULTS: Sixty-six participants completed the
      study. Exercise training did not significantly increase peak oxygen uptake
      compared to control (p = 0.12). Compared to control, insulin resistance improved
      in the pioglitazone group (p = 0.002) but not in the exercise group (p = 0.25).
      There was no measureable effect of pioglitazone or exercise on cognitive
      performance compared to control. CONCLUSION: In this pilot study, pioglitazone
      improved insulin resistance but not cognitive performance in older adults with
      MCI and insulin resistance.

PMID- 25852734
TI  - Lipid levels and renal function decline in pre-dialysis patients.
AB  - BACKGROUND: Little is known about the effect of low-density lipoprotein (LDL)
      cholesterol, triglyceride (TG), and high-density lipoprotein (HDL) cholesterol
      levels on renal function decline in patients receiving specialized pre-dialysis
      care. METHODS: In the prospective PREPARE-2 study, incident patients starting pre
      dialysis care were included when referred to one of the 25 participating Dutch
      specialized pre-dialysis outpatient clinics (2004-2011). Clinical and laboratory
      data were collected every 6 months. A linear mixed model was used to compare
      renal function decline between patients with LDL cholesterol, TG, or HDL
      cholesterol levels above and below the target goals (LDL cholesterol: <2.50
      mmol/l, TG: <2.25 mmol/l, and HDL cholesterol: >=1.00 mmol/l). Additionally the
      HDL/LDL cholesterol ratio was investigated (>=0.4). RESULTS: In our study
      population (n = 306), the median age was 69 years and 70% were male. Patients
      with LDL cholesterol levels above the target of 2.50 mmol/l experienced an
      accelerated renal function decline compared to patients with levels below the
      target (crude additional decline: 0.10 ml/min/1.73 m(2)/month, 95% CI 0.00-0.20;
      p < 0.05). A similar trend was found for TG levels above the target of 2.25
      mmol/l (0.05 ml/min/1.73 m(2)/month, 95% CI -0.06 to 0.16) and for a HDL/LDL
      cholesterol ratio below 0.4 (0.06 ml/min/1.73 m(2)/month, 95% CI -0.05 to 0.18).
      Adjustment for potential confounders resulted in similar results, and the
      exclusion of patients who were prescribed lipid-lowering medication (statin,
      fibrate, or cholesterol absorption inhibitor) resulted in a slightly larger
      estimated effect. CONCLUSION: High levels of LDL cholesterol were associated with
      an accelerated renal function decline, independent of the prescription of lipid
      lowering medication.

PMID- 25852733
TI  - Effects of Tumor Necrosis Factor-alpha on Podocyte Expression of Monocyte
      Chemoattractant Protein-1 and in Diabetic Nephropathy.
AB  - BACKGROUND/AIMS: Tumor necrosis factor (TNF)-alpha is believed to play a role in
      diabetic kidney disease. This study explores the specific effects of TNF-alpha
      with regard to nephropathy-relevant parameters in the podocyte. METHODS: Cultured
      mouse podocytes were treated with recombinant TNF-alpha and assayed for
      production of monocyte chemoattractant protein-1 (MCP-1) by enzyme-linked
      immunosorbent assay (ELISA). TNF-alpha signaling of MCP-1 was elucidated by
      antibodies against TNF receptor (TNFR) 1 or TNFR2 or inhibitors of nuclear factor
      kappaB (NF-kappaB), phosphatidylinositol 3-kinase (PI3K) or Akt. In vivo studies
      were done on male db/m and type 2 diabetic db/db mice. Levels of TNF-alpha and
      MCP-1 were measured by RT-qPCR and ELISA in the urine, kidney and plasma of the
      two cohorts and correlated with albuminuria. RESULTS: Podocytes treated with TNF
      alpha showed a robust increase (~900%) in the secretion of MCP-1, induced in a
      dose- and time-dependent manner. Signaling of MCP-1 expression occurred through
      TNFR2, which was inducible by TNF-alpha ligand, but did not depend on TNFR1. TNF
      alpha then proceeded via the NF-kappaB and the PI3K/Akt systems, based on the
      effectiveness of the inhibitors of those pathways. For in vivo relevance to
      diabetic kidney disease, TNF-alpha and MCP-1 levels were found to be elevated in
      the urine of db/db mice but not in the plasma. CONCLUSION: TNF-alpha potently
      stimulates podocytes to produce MCP-1, utilizing the TNFR2 receptor and the NF
      kappaB and PI3K/Akt pathways. Both TNF-alpha and MCP-1 levels were increased in
      the urine of diabetic db/db mice, correlating with the severity of diabetic
      albuminuria.

PMID- 25852735
TI  - Mapping the global mRNA transcriptome during development of the murine first
      molar.
AB  - The main objective of this study was to map global gene expression in order to
      provide information about the populations of mRNA species participating in murine
      tooth development at 24 h intervals, starting at the 11th embryonic day (E11.5)
      up to the 7th post-natal day (P7). The levels of RNA species expressed during
      murine tooth development were mesured using a total of 58 deoxyoligonucleotide
      microarrays. Microarray data was validated using real-time RT-PCR. Differentially
      expressed genes (p < 0.05) were subjected to bioinformatic analysis to identify
      cellular activities significantly associated with these genes. Using ANOVA the
      microarray data yielded 4362 genes as being differentially expressed from the
      11th embryonic day (E11.5) up to 7 days post-natal (P7), 1921 of these being
      genes without known functions. The remaining 2441 genes were subjected to further
      statistical analysis using a supervised procedure. Bioinformatic analysis results
      for each time-point studied suggests that the main molecular functions associated
      with genes expressed at the early pre-natal stages (E12.5-E18.5) were cell cycle
      progression, cell morphology, lipid metabolism, cellular growth, proliferation,
      senescence and apoptosis, whereas most genes expressed at post-natal and
      secretory stages (P0-P7) were significantly associated with regulation of cell
      migration, biosynthesis, differentiation, oxidative stress, polarization and cell
      death. Differentially expressed genes (DE) not described earlier during murine
      tooth development; Inositol 1, 4, 5-triphosphate receptor 3 (Itpr3),
      metallothionein 1(Mt1), cyclin-dependent kinase 4 (Cdk4), cathepsin D (Ctsd),
      keratin complex 2, basic, gene 6a (Krt2-6a), cofilin 1, non-muscle (Cfl1), cyclin
      2 (Ccnd2), were verified by real-time RT-PCR. 

PMID- 25852736
TI  - Integrated genomic and BMI analysis for type 2 diabetes risk assessment.
AB  - Type 2 Diabetes (T2D) is a chronic disease arising from the development of
      insulin absence or resistance within the body, and a complex interplay of
      environmental and genetic factors. The incidence of T2D has increased throughout
      the last few decades, together with the occurrence of the obesity epidemic. The
      consideration of variants identified by Genome Wide Association Studies (GWAS)
      into risk assessment models for T2D could aid in the identification of at-risk
      patients who could benefit from preventive medicine. In this study, we build
      several risk assessment models, evaluated with two different classification
      approaches (Logistic Regression and Neural Networks), to measure the effect of
      including genetic information in the prediction of T2D. We used data from to the
      Original and the Offspring cohorts of the Framingham Heart Study, which provides
      phenotypic and genetic information for 5245 subjects (4306 controls and 939
      cases). Models were built by using several covariates: gender, exposure time,
      cohort, body mass index (BMI), and 65 SNPs associated to T2D. We fitted Logistic
      Regressions and Bayesian Regularized Neural Networks and then assessed their
      predictive ability by using a ten-fold cross validation. We found that the
      inclusion of genetic information into the risk assessment models increased the
      predictive ability by 2%, when compared to the baseline model. Furthermore, the
      models that included BMI at the onset of diabetes as a possible effector, gave an
      improvement of 6% in the area under the curve derived from the ROC analysis. The
      highest AUC achieved (0.75) belonged to the model that included BMI, and a
      genetic score based on the 65 established T2D-associated SNPs. Finally, the
      inclusion of SNPs and BMI raised predictive ability in all models as expected;
      however, results from the AUC in Neural Networks and Logistic Regression did not
      differ significantly in their prediction accuracy. 

PMID- 25852738
TI  - Telomeric aging: mitotic clock or stress indicator?

PMID- 25852737
TI  - Mucin glycan foraging in the human gut microbiome.
AB  - The availability of host and dietary carbohydrates in the gastrointestinal (GI)
      tract plays a key role in shaping the structure-function of the microbiota. In
      particular, some gut bacteria have the ability to forage on glycans provided by
      the mucus layer covering the GI tract. The O-glycan structures present in mucin
      are diverse and complex, consisting predominantly of core 1-4 mucin-type O
      glycans containing alpha- and beta- linked N-acetyl-galactosamine, galactose and
      N-acetyl-glucosamine. These core structures are further elongated and frequently
      modified by fucose and sialic acid sugar residues via alpha1,2/3/4 and alpha2,3/6
      linkages, respectively. The ability to metabolize these mucin O-linked
      oligosaccharides is likely to be a key factor in determining which bacterial
      species colonize the mucosal surface. Due to their proximity to the immune
      system, mucin-degrading bacteria are in a prime location to influence the host
      response. However, despite the growing number of bacterial genome sequences
      available from mucin degraders, our knowledge on the structural requirements for
      mucin degradation by gut bacteria remains fragmented. This is largely due to the
      limited number of functionally characterized enzymes and the lack of studies
      correlating the specificity of these enzymes with the ability of the strain to
      degrade and utilize mucin and mucin glycans. This review focuses on recent
      findings unraveling the molecular strategies used by mucin-degrading bacteria to
      utilize host glycans, adapt to the mucosal environment, and influence human
      health. 

PMID- 25852740
TI  - Genetic improvement of Pacific white shrimp [Penaeus (Litopenaeus) vannamei]:
      perspectives for genomic selection.
AB  - The uses of breeding programs for the Pacific white shrimp [Penaeus (Litopenaeus)
      vannamei] based on mixed linear models with pedigreed data are described. The
      application of these classic breeding methods yielded continuous progress of
      great value to increase the profitability of the shrimp industry in several
      countries. Recent advances in such areas as genomics in shrimp will allow for the
      development of new breeding programs in the near future that will increase
      genetic progress. In particular, these novel techniques may help increase disease
      resistance to specific emerging diseases, which is today a very important
      component of shrimp breeding programs. Thanks to increased selection accuracy,
      simulated genetic advance using genomic selection for survival to a disease
      challenge was up to 2.6 times that of phenotypic sib selection. 

PMID- 25852739
TI  - On the road with WRAP53beta: guardian of Cajal bodies and genome integrity.
AB  - The WRAP53 gene encodes both an antisense transcript (WRAP53alpha) that
      stabilizes the tumor suppressor p53 and a protein (WRAP53beta) involved in
      maintenance of Cajal bodies, telomere elongation and DNA repair. WRAP53beta is
      one of many proteins containing WD40 domains, known to mediate a variety of
      cellular processes. These proteins lack enzymatic activity, acting instead as
      platforms for the assembly of large complexes of proteins and RNAs thus
      facilitating their interactions. WRAP53beta mediates site-specific interactions
      between Cajal body factors and DNA repair proteins. Moreover, dysfunction of this
      protein has been linked to premature aging, cancer and neurodegeneration. Here we
      summarize the current state of knowledge concerning the multifaceted roles of
      WRAP53beta in intracellular trafficking, formation of the Cajal body, DNA repair
      and maintenance of genomic integrity and discuss potential crosstalk between
      these processes. 

PMID- 25852741
TI  - Nuclear envelope and genome interactions in cell fate.
AB  - The eukaryotic cell nucleus houses an organism's genome and is the location
      within the cell where all signaling induced and development-driven gene
      expression programs are ultimately specified. The genome is enclosed and
      separated from the cytoplasm by the nuclear envelope (NE), a double-lipid
      membrane bilayer, which contains a large variety of trans-membrane and associated
      protein complexes. In recent years, research regarding multiple aspects of the
      cell nucleus points to a highly dynamic and coordinated concert of efforts
      between chromatin and the NE in regulation of gene expression. Details of how
      this concert is orchestrated and how it directs cell differentiation and disease
      are coming to light at a rapid pace. Here we review existing and emerging
      concepts of how interactions between the genome and the NE may contribute to
      tissue specific gene expression programs to determine cell fate. 

PMID- 25852743
TI  - Metatranscriptomic analyses of honey bee colonies.
AB  - Honey bees face numerous biotic threats from viruses to bacteria, fungi,
      protists, and mites. Here we describe a thorough analysis of microbes harbored by
      worker honey bees collected from field colonies in geographically distinct
      regions of Turkey. Turkey is one of the World's most important centers of
      apiculture, harboring five subspecies of Apis mellifera L., approximately 20% of
      the honey bee subspecies in the world. We use deep ILLUMINA-based RNA sequencing
      to capture RNA species for the honey bee and a sampling of all non-endogenous
      species carried by bees. After trimming and mapping these reads to the honey bee
      genome, approximately 10% of the sequences (9-10 million reads per library)
      remained. These were then mapped to a curated set of public sequences containing
      ca. Sixty megabase-pairs of sequence representing known microbial species
      associated with honey bees. Levels of key honey bee pathogens were confirmed
      using quantitative PCR screens. We contrast microbial matches across different
      sites in Turkey, showing new country recordings of Lake Sinai virus, two
      Spiroplasma bacterium species, symbionts Candidatus Schmidhempelia bombi,
      Frischella perrara, Snodgrassella alvi, Gilliamella apicola, Lactobacillus spp.),
      neogregarines, and a trypanosome species. By using metagenomic analysis, this
      study also reveals deep molecular evidence for the presence of bacterial
      pathogens (Melissococcus plutonius, Paenibacillus larvae), Varroa destructor-1
      virus, Sacbrood virus, and fungi. Despite this effort we did not detect KBV,
      SBPV, Tobacco ringspot virus, VdMLV (Varroa Macula like virus), Acarapis spp.,
      Tropilaeleps spp. and Apocephalus (phorid fly). We discuss possible impacts of
      management practices and honey bee subspecies on microbial retinues. The
      described workflow and curated microbial database will be generally useful for
      microbial surveys of healthy and declining honey bees. 

PMID- 25852742
TI  - Regulators of homologous recombination repair as novel targets for cancer
      treatment.
AB  - To cope with DNA damage, cells possess a complex signaling network called the
      'DNA damage response', which coordinates cell cycle control with DNA repair. The
      importance of this network is underscored by the cancer predisposition that
      frequently goes along with hereditary mutations in DNA repair genes. One
      especially important DNA repair pathway in this respect is homologous
      recombination (HR) repair. Defects in HR repair are observed in various cancers,
      including hereditary breast, and ovarian cancer. Intriguingly, tumor cells with
      defective HR repair show increased sensitivity to chemotherapeutic reagents,
      including platinum-containing agents. These observations suggest that HR
      proficient tumor cells might be sensitized to chemotherapeutics if HR repair
      could be therapeutically inactivated. HR repair is an extensively regulated
      process, which depends strongly on the activity of various other pathways,
      including cell cycle pathways, protein-control pathways, and growth factor
      activated receptor signaling pathways. In this review, we discuss how the
      mechanistic wiring of HR is controlled by cell-intrinsic or extracellular
      pathways. Furthermore, we have performed a meta-analysis on available genome-wide
      RNA interference studies to identify additional pathways that control HR repair.
      Finally, we discuss how these HR-regulatory pathways may provide therapeutic
      targets in the context of radio/chemosensitization. 

PMID- 25852744
TI  - Long-term survival in a child with severe encephalopathy, multiple respiratory
      chain deficiency and GFM1 mutations.
AB  - BACKGROUND: Mitochondrial diseases due to deficiencies in the mitochondrial
      oxidative phosphorylation system (OXPHOS) can be associated with nuclear genes
      involved in mitochondrial translation, causing heterogeneous early onset and
      often fatal phenotypes. CASE REPORT: The authors describe the clinical features
      and diagnostic workup of an infant who presented with an early onset severe
      encephalopathy, spastic-dystonic tetraparesis, failure to thrive, seizures and
      persistent lactic acidemia. Brain imaging revealed thinning of the corpus
      callosum and diffuse alteration of white matter signal. Genetic investigation
      confirmed two novel mutations in the GFM1 gene, encoding the mitochondrial
      translation elongation factor G1 (mtEFG1), resulting in combined deficiencies of
      OXPHOS. DISCUSSION: The patient shares multiple clinical, laboratory and
      radiological similarities with the 11 reported patients with mutations involving
      this gene, but presents with a stable clinical course without metabolic
      decompensations, rather than a rapidly progressive fatal course. Defects in GFM1
      gene confer high susceptibility to neurologic or hepatic dysfunction and this is,
      to the best of our knowledge, the first described patient who has survived beyond
      early childhood. Reporting of such cases is essential so as to delineate the key
      clinical and neuroradiological features of this disease and provide a more
      comprehensive view of its prognosis.

PMID- 25852745
TI  - The foundation of precision medicine: integration of electronic health records
      with genomics through basic, clinical, and translational research.

PMID- 25852746
TI  - Fecal egg counts for gastrointestinal nematodes are associated with a
      polymorphism in the MHC-DRB1 gene in the Iranian Ghezel sheep breed.
AB  - Genetic variation among sheep breeds in resistance to gastrointestinal nematodes
      (GIN) has been demonstrated in several production environments. Relationships
      between the ovine major histocompatibility complex and resistance to GIN have
      been studied, but few studies have systematically examined this issue in less
      developed and semi-arid regions. The aim of the current study was to explore
      associations between fecal worm egg counts (FEC) for several GIN and
      polymorphisms in the DRB1 gene. One hundred male lambs were selected at 4-6
      months of age from weaned animals in five flocks (n = 20 per flock). Body weights
      were determined, FAMACHA scores based on color of the ocular mucous membranes
      were assigned as an indicator of anemia, and blood and fecal samples were
      collected twice to evaluate FEC and blood packed cell volume (PCV) and for DNA
      isolation. A repeated-measures analysis of variance was used to test effects of
      genotype on FEC. The model included fixed effects of flock, genotype, time of
      measurement (1 or 2), and flock * time and genoype * time interactions, and a
      random (repeated) effect of lamb. Two genotypes (A1A1 and A1A2) were observed
      following digestion of Region 1 of Ovar-DRB1 with PstI. Genotypic frequencies
      were 0.73 for A1A1 and 0.27 for A1A2. FEC differed between Ovar_DRB1 genotypes
      A1A1 and A1A2 for Marshallagia marshalli, Strongyle, and total nematode FEC.
      Observed FEC were 30-41% lower for genotype A1A1. Differences among genotypes
      were consistent across measurement times, with no effect of genotype *
      measurement time interaction for any parasite class (P >= 0.34). A significant
      association was observed between FAMACHA scores and lamb PCV, and the residual
      correlation between these two variables was -0.51 (P < 0.001). FAMACHA scores can
      thus be used to detect differences among lambs in PCV, and polymorphic markers of
      Ovar-DRB1 have potential value as an indicator of parasite resistance in applied
      animal breeding programs on sheep farms in this region. 

PMID- 25852748
TI  - SNeP: a tool to estimate trends in recent effective population size trajectories
      using genome-wide SNP data.
AB  - Effective population size (Ne ) is a key population genetic parameter that
      describes the amount of genetic drift in a population. Estimating Ne has been
      subject to much research over the last 80 years. Methods to estimate Ne from
      linkage disequilibrium (LD) were developed ~40 years ago but depend on the
      availability of large amounts of genetic marker data that only the most recent
      advances in DNA technology have made available. Here we introduce SNeP, a
      multithreaded tool to perform the estimate of Ne using LD using the standard
      PLINK input file format (.ped and.map files) or by using LD values calculated
      using other software. Through SNeP the user can apply several corrections to take
      account of sample size, mutation, phasing, and recombination rate. Each variable
      involved in the computation such as the binning parameters or the chromosomes to
      include in the analysis can be modified. When applied to published datasets, SNeP
      produced results closely comparable with those obtained in the original studies.
      The use of SNeP to estimate Ne trends can improve understanding of population
      demography in the recent past, provided a sufficient number of SNPs and their
      physical position in the genome are available. Binaries for the most common
      operating systems are available at
      https://sourceforge.net/projects/snepnetrends/. 

PMID- 25852747
TI  - DNA polymerase gamma and disease: what we have learned from yeast.
AB  - Mip1 is the Saccharomyces cerevisiae DNA polymerase gamma (Pol gamma), which is
      responsible for the replication of mitochondrial DNA (mtDNA). It belongs to the
      family A of the DNA polymerases and it is orthologs to human POLGA. In humans,
      mutations in POLG(1) cause many mitochondrial pathologies, such as progressive
      external ophthalmoplegia (PEO), Alpers' syndrome, and ataxia-neuropathy syndrome,
      all of which present instability of mtDNA, which results in impaired
      mitochondrial function in several tissues with variable degrees of severity. In
      this review, we summarize the genetic and biochemical knowledge published on
      yeast mitochondrial DNA polymerase from 1989, when the MIP1 gene was first
      cloned, up until now. The role of yeast is particularly emphasized in (i)
      validating the pathological mutations found in human POLG and modeled in MIP1,
      (ii) determining the molecular defects caused by these mutations and (iii)
      finding the correlation between mutations/polymorphisms in POLGA and mtDNA
      toxicity induced by specific drugs. We also describe recent findings regarding
      the discovery of molecules able to rescue the phenotypic defects caused by
      pathological mutations in Mip1, and the construction of a model system in which
      the human Pol gamma holoenzyme is expressed in yeast and complements the loss of
      Mip1. 

PMID- 25852749
TI  - Mutations of mitochondrial genome in carotid atherosclerosis.
AB  - With aim of detection the spectrum of mitochondrial DNA mutations in patients
      with carotid atherosclerosis from Moscow Region, we used a Roche 454 high
      throughput sequencing of the whole mitochondrial genome. We have found that the
      presence of a number of homoplasmic mitochondrial DNA mutations in genes of 16S
      ribosomal RNA, subunits 2, 4, and 5 NADH dehydrogenase, subunits 1 and 2
      cytochrome C oxidase, subunit 6 ATP-synthase, tRNA- Leu 2 and cytochrome B
      differed between conventionally healthy participants of the study and patients
      with carotid atherosclerosis. We also found heteroplasmic mutations, including
      insertions one or several nucleotides, that occurred more frequently in
      mitochondrial DNA of conventionally healthy participants of the study or patients
      with atherosclerotic lesions. 

PMID- 25852750
TI  - The phenotypic expression of mitochondrial tRNA-mutations can be modulated by
      either mitochondrial leucyl-tRNA synthetase or the C-terminal domain thereof.
AB  - Mutations in mitochondrial (mt) DNA determine important human diseases. The
      majority of the known pathogenic mutations are located in transfer RNA (tRNA)
      genes and are responsible for a wide range of currently untreatable disorders.
      Experimental evidence both in yeast and in human cells has shown that the
      detrimental effects of mt-tRNA point mutations can be attenuated by increasing
      the expression of the cognate mt-aminoacyl-tRNA synthetases (aaRSs). In addition,
      constitutive high levels of isoleucyl-tRNA syntethase have been shown to reduce
      the penetrance of a homoplasmic mutation in mt-tRNA(Ile) in a small kindred. More
      recently, we showed that the isolated carboxy-terminal domain of human mt-leucyl
      tRNA synthetase (LeuRS-Cterm) localizes to mitochondria and ameliorates the
      energetic defect in transmitochondrial cybrids carrying mutations either in the
      cognate mt-tRNA(Leu(UUR)) or in the non-cognate mt-tRNA(Ile) gene. Since the mt
      LeuRS-Cterm does not possess catalytic activity, its rescuing ability is most
      likely mediated by a chaperon-like effect, consisting in the stabilization of the
      tRNA structure altered by the mutation. All together, these observations open
      potential therapeutic options for mt-tRNA mutations-associated diseases. 

PMID- 25852753
TI  - A comparison of two invagination techniques for pancreatojejunostomy after
      pancreatoduodenectomy.
AB  - Background. The aim of the study was to compare two invagination techniques for
      pancreatojejunostomy after pancreatoduodenectomy. Methods. For effective
      prevention of the development of pancreatic leakage, we modified invagination
      technique that we term the "serous touch." We analysed the diameter of the main
      pancreatic duct, the texture of the remnant pancreas, the method of the
      reconstruction, pancreatic external drainage, anastomotic procedure time,
      histopathological examination, and postoperative complications. Results. Fifty
      two patients underwent pancreatoduodenectomy with pancreatojejunostomy using
      "serous touch" technique (ST group) and 52 classic pancreatojejunostomy (C
      group). In the ST group one patient (1.9%) was diagnosed as grade B pancreatic
      fistula, and no patient experienced fistula grade A or C. In the C group 6
      patients (11.5%) were diagnosed as fistula grade A, 1 (1.9%) patient as fistula
      grade B, and 1 (1.9%) patient as fistula grade C. There was a significant
      statistical difference in incidents of pancreatic fistula (P < 0.05) and no
      statistical difference in other postoperative complications or mortality in
      comparison group. Anastomosis time was statistically shorter in the ST group.
      Conclusions. "Serous touch" technique appeared to be easy, safe, associated with
      fewer incidences of pancreatic fistulas, and less time consuming in comparison
      with classical pancreatojejunostomy. 

PMID- 25852751
TI  - Mononuclear cells and vascular repair in HHT.
AB  - Hereditary hemorrhagic telangiectasia (HHT) or Rendu-Osler-Weber disease is a
      rare genetic vascular disorder known for its endothelial dysplasia causing
      arteriovenous malformations and severe bleedings. HHT-1 and HHT-2 are the most
      prevalent variants and are caused by heterozygous mutations in endoglin and
      activin receptor-like kinase 1, respectively. An undervalued aspect of the
      disease is that HHT patients experience persistent inflammation. Although
      endothelial and mural cells have been the main research focus trying to unravel
      the mechanism behind the disease, wound healing is a process with a delicate
      balance between inflammatory and vascular cells. Inflammatory cells are part of
      the mononuclear cells (MNCs) fraction, and can, next to eliciting an immune
      response, also have angiogenic potential. This biphasic effect of MNC can hold a
      promising mechanism to further elucidate treatment strategies for HHT patients.
      Before MNC are able to contribute to repair, they need to home to and retain in
      ischemic and damaged tissue. Directed migration (homing) of MNCs following tissue
      damage is regulated by the stromal cell derived factor 1 (SDF1). MNCs that
      express the C-X-C chemokine receptor 4 (CXCR4) migrate toward the tightly
      regulated gradient of SDF1. This directed migration of monocytes and lymphocytes
      can be inhibited by dipeptidyl peptidase 4 (DPP4). Interestingly, MNC of HHT
      patients express elevated levels of DPP4 and show impaired homing toward damaged
      tissue. Impaired homing capacity of the MNCs might therefore contribute to the
      impaired angiogenesis and tissue repair observed in HHT patients. This review
      summarizes recent studies regarding the role of MNCs in the etiology of HHT and
      vascular repair, and evaluates the efficacy of DPP4 inhibition in tissue
      integrity and repair. 

PMID- 25852754
TI  - Ebola virus disease 2013-2014 outbreak in west Africa: an analysis of the
      epidemic spread and response.
AB  - The Ebola virus epidemic burst in West Africa in late 2013, started in Guinea,
      reached in a few months an alarming diffusion, actually involving several
      countries (Liberia, Sierra Leone, Nigeria, Senegal, and Mali). Guinea and
      Liberia, the first nations affected by the outbreak, have put in place measures
      to contain the spread, supported by international organizations; then they were
      followed by the other nations affected. In the present EVD outbreak, the
      geographical spread of the virus has followed a new route: the achievement of
      large urban areas at an early stage of the epidemic has led to an unprecedented
      diffusion, featuring the largest outbreak of EVD of all time. This has caused
      significant concerns all over the world: the potential reaching of far countries
      from endemic areas, mainly through fast transports, induced several countries to
      issue information documents and health supervision for individuals going to or
      coming from the areas at risk. In this paper the geographical spread of the
      epidemic was analyzed, assessing the sequential appearance of cases by geographic
      area, considering the increase in cases and mortality according to affected
      nations. The measures implemented by each government and international
      organizations to contain the outbreak, and their effectiveness, were also
      evaluated. 

PMID- 25852752
TI  - Drosophila melanogaster Hsp22: a mitochondrial small heat shock protein
      influencing the aging process.
AB  - Mitochondria are involved in many key cellular processes and therefore need to
      rely on good protein quality control (PQC). Three types of mechanisms are in
      place to insure mitochondrial protein integrity: reactive oxygen species
      scavenging by anti-oxidant enzymes, protein folding/degradation by molecular
      chaperones and proteases and clearance of defective mitochondria by mitophagy.
      Drosophila melanogaster Hsp22 is part of the molecular chaperone axis of the PQC
      and is characterized by its intra-mitochondrial localization and preferential
      expression during aging. As a stress biomarker, the level of its expression
      during aging has been shown to partially predict the remaining lifespan of flies.
      Since over-expression of this small heat shock protein increases lifespan and
      resistance to stress, Hsp22 most likely has a positive effect on mitochondrial
      integrity. Accordingly, Hsp22 has recently been implicated in the mitochondrial
      unfolding protein response of flies. This review will summarize the key findings
      on D. melanogaster Hsp22 and emphasis on its links with the aging process. 

PMID- 25852755
TI  - Beneficial effects of coculturing synovial derived mesenchymal stem cells with
      meniscus fibrochondrocytes are mediated by fibroblast growth factor 1: increased
      proliferation and collagen synthesis.
AB  - Meniscus reconstruction is in great need for orthopedic surgeons. Meniscal
      fibrochondrocytes transplantation was proposed to regenerate functional meniscus,
      with limited donor supply. We hypothesized that coculture of synovial mesenchymal
      stem cells (SSC) with meniscal fibrochondrocytes (me-CH) can support matrix
      production of me-CH, thus reducing the number of me-CH needed for meniscus
      reconstruction. A pellet coculture system of human SSC and me-CH was used in this
      study. Enhanced glycosaminoglycans (GAG) in coculture pellets were demonstrated
      by Alcian blue staining and GAG quantification, when compared to monoculture.
      More collagen synthesis was shown in coculture pellets by hydroxyproline assay.
      Increased proliferation of me-CH was observed in coculture. Data from BrdU
      staining and ELISA demonstrated that conditioned medium of SSCs enhanced the
      proliferation and collagen synthesis of me-CH, and this effect was blocked by
      neutralizing antibody against fibroblast growth factor 1 (FGF1). Western blot
      showed that conditioned medium of SSCs can activate mitogen-activated protein
      kinase (MAPK) signaling pathways by increasing the phosphorylation of mitogen
      activated regulated protein kinase 1/2 (MEK) and extracellular-signal-regulated
      kinases 1/2 (ERK). Overall, this study provided evidence that synovial MSCs can
      support proliferation and collagen synthesis of fibrochondrocytes, by secreting
      FGF1. Coimplantation of SSC and me-CH could be a useful strategy for
      reconstructing meniscus. 

PMID- 25852756
TI  - Anthracosis of the lungs: etiology, clinical manifestations and diagnosis: a
      review.
AB  - Anthracosis of the lungs is black discoloration of bronchial mucosa that can
      occlude bronchial lumen and is associated with bronchial anthracofibrosis (BAF).
      This disease usually presents with a chronic course of dyspnea and or cough in an
      elderly non-smoker woman or man. In addition, concomitant exposure to dust and
      wood smoke is the most postulated etiology for anthracosis. Pulmonary function
      tests usually show an obstructive pattern with no response to bronchodilators and
      normal DLCO, but some cases with restrictive pattern have also been seen.
      Computed tomography (CT) may show more specific findings such as lymph node or
      bronchial calcification and mass lesions. Final diagnosis can be made by
      bronchoscopy when obtaining samples for tuberculosis (TB), which is the most
      common disease associated with BAF. Endobronchial ultrasound shows a hypoechoic
      scattered nodular pattern in adjacent lymph nodes, which is unique to
      anthracosis. Treatment is very similar to that of chronic obstructive pulmonary
      disease (COPD) with a chronic course and low mortality. This review discusses
      this disease as a separate entity; hence, anthracosis should be added to the list
      of obstructive lung diseases and benign mass lesions and differentiated from
      biomass induced COPD. 

PMID- 25852757
TI  - Clinical and radiographic manifestations and treatment outcome of pulmonary
      tuberculosis in the elderly in khuzestan, southwest iran.
AB  - BACKGROUND: Presentation of pulmonary tuberculosis (PTB) in the elderly is
      expected to be different from that in younger patients because of the
      debilitating factors and comorbidities. This issue should be considered in the
      national tuberculosis programs of countries. The purpose of this study was to
      evaluate the differences in the clinical and radiographic manifestations and
      treatment outcomes of PTB between the elderly and young patients. MATERIALS AND
      METHODS: This study was conducted as part of a mega project on tuberculosis by
      the Infectious and Tropical Diseases Research Centre affiliated to Ahvaz
      Jundishapur University of Medical Sciences. We retrospectively analyzed the
      medical records of 2,080 relatively young (18-64 years old at the time of
      diagnosis) and 346 elderly (>=65 years) PTB patients, who had been recently
      diagnosed and treated in the TB unit of Khuzestan Health Center from 2005 to
      2010. RESULTS: Dyspnea and hemoptysis were the most common symptoms and the
      frequency of positive sputum smear -AFB was lower in the elderly PTB patients. On
      chest X-ray, elderly patients were less likely to have cavitation in comparison
      with younger patients. The frequency of favourable treatment outcome in the
      elderly was significantly lower than that in younger patients (64% vs. 77%, P =
      0.003). CONCLUSION: Dyspnea, weight loss and hemoptysis were more common in the
      elderly PTB patients. Chest X-ray showed less frequent typical findings of active
      PTB such as cavitation; and microscopic examination showed fewer sputum smear AFB
      positive cases in the elderly. The treatment outcome was less favorable in the
      elderly compared to younger TB patients.

PMID- 25852758
TI  - Predictors of non-invasive ventilation failure in severe respiratory failure due
      to community acquired pneumonia.
AB  - BACKGROUND: Non-invasive ventilation (NIV) has been used for acute respiratory
      failure to avoid endotracheal intubation and intensive care admission. Few
      studies have assessed the usefulness of NIV in patients with severe community
      acquired pneumonia (CAP). The use of NIV in severe CAP is controversial because
      there is a greater variability in success compared to other pulmonary conditions.
      MATERIALS AND METHODS: We retrospectively followed 130 patients with CAP and
      severe acute respiratory failure (PaO2/FiO2 < 250) admitted to a Respiratory
      Monitoring Unit (RMU) and underwent NIV. We assessed predictors of NIV failure
      and hospital mortality using univariate and multivariate analyses. RESULTS: NIV
      failed in 26 patients (20.0%). Higher chest X-ray score at admission, higher
      heart rate after 1 hour of NIV, and a higher alveolar-arteriolar gradient (A
      aDO2) after 24 hours of NIV each independently predicted NIV failure. Higher
      chest X ray score, higher LDH at admission, higher heart rate after 24 hours of
      NIV and higher A-aDO2 after 24 hours of NIV were directly related to hospital
      mortality. CONCLUSION: NIV treatment had high rate of success. Successful
      treatment is related to less lung involvement and to early good response to NIV
      and continuous improvement in clinical response.

PMID- 25852760
TI  - Qualification study of two genomic DNA extraction methods in different clinical
      samples.
AB  - INTRODUCTION: The purity of genomic DNA (gDNA) extracted from different clinical
      specimens optimizes sensitivity of polymerase chain reaction (PCR) assays. This
      study attempted to compare two different DNA extraction techniques namely salting
      out and classic phenol-chloroform. MATERIALS AND METHODS: Qualification of two
      different DNA extraction techniques for 634 clinical specimens highly suspected
      of having mycobacterial infection was performed. Genomic DNA was extracted from
      330 clinical samples using phenol-chloroform and 304 by non-toxic salting-out.
      Qualification of obtained gDNA was done through amplification of internal
      controls, beta-actin and beta-globin. RESULTS: beta-actin-positive was detected
      in 279/330 (84%) and 272/304 (89%) samples by phenol-chloroform technique and
      salting-out, respectively. PCR inhibitor was found for the gDNA of 13/304 (4%)
      patient samples were negative by beta-actin and beta-globin tests via salting-out
      technique in comparison with gDNAs from 27/330 (8.5%) samples extracted by phenol
      chloroform procedure. No statistically significant difference was found between
      phenol-chloroform technique and salting-out for 385 sputum, 29 bronchoalveolar
      lavage (BAL), 105 gastric washing, and 38 body fluid (P=0.04) samples. This
      illustrates that both techniques have the same quality for extracting gDNA.
      CONCLUSION: This study discloses salting-out as a non-toxic DNA extraction
      procedure with a superior time-efficiency and cost-effectiveness in comparison
      with phenol-chloroform and it can be routinely used in resource-limited
      laboratory settings.

PMID- 25852759
TI  - Diagnostic Accuracy of Chest Ultrasonography versus Chest Radiography for
      Identification of Pneumothorax: A Systematic Review and Meta-Analysis.
AB  - BACKGROUND: Early detection of pneumothorax is critically important. Several
      studies have shown that chest ultrasonography (CUS) is a highly sensitive and
      specific tool. The present systematic review and meta-analysis was designed to
      evaluate the diagnostic accuracy of CUS and chest radiography (CXR) for detection
      of pneumothorax. MATERIALS AND METHODS: The literature search was conducted using
      PubMed, EMBASE, Cochrane, CINAHL, SUMSearch, Trip databases, and review article
      references. Eligible articles were defined as diagnostic studies on patients
      suspected for pneumothorax who underwent chest computed tomography (CT) scan and
      those assessing the screening role of CUS and CXR. RESULTS: The analysis showed
      the pooled sensitivity and specificity of CUS were 0.87 (95% CI: 0.81-0.92; I2=
      88.89, P<0.001) and 0.99 (95% CI: 0.98-0.99; I2= 86.46, P<0.001), respectively.
      The pooled sensitivity and specificity of CXR were 0.46 (95% CI: 0.36-0.56; I2=
      85.34, P<0.001) and 1.0 (95% CI: 0.99-1.0; I2= 79.67, P<0.001), respectively. The
      Meta regression showed that the sensitivity (0.88; 95% CI: 0.82 - 0.94) and
      specificity (0.99; 95% CI: 0.98 - 1.00) of ultrasound performed by the emergency
      physician was higher than by non-emergency physician. Non-trauma setting was
      associated with higher pooled sensitivity (0.90; 95% CI: 0.83 - 0.98) and lower
      specificity (0.97; 95% CI: 0.95 - 0.99). CONCLUSION: The present meta-analysis
      showed that the diagnostic accuracy of CUS was higher than supine CXR for
      detection of pneumothorax. It seems that CUS is superior to CXR in detection of
      pneumothorax, even after adjusting for possible sources of heterogeneity.

PMID- 25852761
TI  - Evaluation of bronchoscopy complications in a tertiary health care center.
AB  - BACKGROUND: Bronchoscopy is a technique of visualizing the inside of the airways
      for diagnostic and therapeutic purposes. This study was performed to determine
      the complications of bronchoscopy in a tertiary health-care center. MATERIALS AND
      METHODS: This study had as descriptive cross sectional design. Four hundred adult
      patients between 16 to 85 years, who underwent bronchoscopy with a same method
      and same device and had no underlying disease, were consecutively enrolled.
      RESULTS: Bronchoscopy complications were seen in 13 patients (3.25%) including
      bleeding (four cases), pneumothorax (three cases), collapse (four cases), and
      infection (two cases). There was no association between complications and age,
      sex, bronchoscopy indications and findings (P > 0.05). CONCLUSION: According to
      the obtained results, it may be concluded that bronchoscopy can be performed
      safely whenever indicated. Complications occurred were minor and self limiting.

PMID- 25852762
TI  - A piece of broken metal from intubation stylet retained in tracheobronchial tree:
      a case report.
AB  - Intubation stylets are still being used in many medical centers for difficult
      intubations. Although very rare, it may break inside the trachea during
      endotracheal intubation despite routine pre-assessments by anesthesiologists and
      may surprisingly move deep into the tracheobronchial tree. In this case report,
      we describe a rare complication after stylet or guide-wire intubation in a
      patient in whom, a broken piece of metal guide remained in his tracheobronchial
      tree for 3 days. A 62 year-old man was admitted to our hospital with the chief
      complaint of functional class 3 dyspnea. The patient was a known case of chronic
      obstructive pulmonary disease (COPD) from 3 years ago with a history of heavy
      smoking (40 p/y) and oral opioid usage. We report a case with an unrecognized
      broken piece of stylet in his trachea and left main bronchus, which was later
      detected by CT scan and extracted before causing pressure rise symptoms in the
      airway. Despite precise evaluation before use, signs of breakage in the stylet
      may be missed and consequently, it may break inside the trachea and result in
      serious complications. It is strongly recommended that the anesthesiologists pay
      attention to the sounds and movements of the instruments. This article also
      briefly reviews the most serious reported complications due to stylet breakage. 

PMID- 25852763
TI  - Huge hilar carcinoid tumor resected by transsternal pneumonectomy: a case
      presentation.
AB  - Carcinoid tumors comprise an uncommon group of pulmonary neoplasms with
      neuroendocrine origin. In comparison with typical carcinoid tumors, atypical
      tumors are less common and more aggressive. We present a 35-year old female with
      atypical carcinoid tumor. The mass was located centrally and transsternal
      pneumonectomy was performed to resect the tumor. 

PMID- 25852764
TI  - Unilateral pulmonary artery agenesis in an adult patient with cough and
      hemoptysis: a case report.
AB  - Unilateral pulmonary artery agenesis (UPAA) is an uncommon congenital anomaly and
      most patients present in neonatal period with respiratory symptoms. Left-sided
      pulmonary artery agenesis is less frequent than right-sided and is sometimes
      associated with cardiac anomalies. We report a patient with a history of repaired
      ventricular septal defect, who presented with cough and hemoptysis and the
      diagnosis of UPAA was made. 

PMID- 25852765
TI  - Erratum to "Ameliorating Adriamycin-Induced Chronic Kidney Disease in Rats by
      Orally Administrated Cardiotoxin from Naja naja atra Venom".
AB  - [This corrects the article DOI: 10.1155/2014/621756.]. 

PMID- 25852766
TI  - Oldenlandia diffusa Promotes Antiproliferative and Apoptotic Effects in a Rat
      Hepatocellular Carcinoma with Liver Cirrhosis.
AB  - Oldenlandia diffusa (OD) is commonly used with various diseases such as cancer,
      arthritis, and autoimmune disease. Liver cirrhosis is a predominant risk factor
      for hepatocellular carcinoma (HCC). Here, we show that the therapeutic effect of
      OD, which was investigated both in vitro and chemically, induced HCC model. OD
      significantly enhanced apoptosis and antiproliferative activity and reduced
      migration ability of HCC cells. In vivo, OD was treated twice a day for 28 days
      after confirmed HCC model through 2-[(18)F]-fluoro-2-deoxy-D-glucose ((18)F-FDG)
      imaging. The survival in OD treated groups was shown to have a greater
      therapeutic effect than the control group. 28 days after OD treatment, OD treated
      groups resulted in a significant reduction in tumor number, size, (18)F-FDG
      uptake, and serum levels such as alanine transaminase, aspartate transaminase,
      and alkaline phosphate compared to the control group. Also, proliferated cells in
      tumor sites by OD were reduced compared to the control group. Furthermore,
      several rats in OD treated group survived over 60 days and liver morphology of
      these rats showed the difference between tumor mass and normal tissue. These
      results suggest that OD may have antiproliferative activity, inhibition of
      metastasis, and apoptotic effects in chemically induced HCC model and can have
      the potential use for clinical application as anticancer drug of the herbal
      extract. 

PMID- 25852767
TI  - Vitis vinifera (Muscat Variety) Seed Ethanolic Extract Preserves Activity Levels
      of Enzymes and Histology of the Liver in Adult Male Rats with Diabetes.
AB  - The effect of V. vinifera seeds on carbohydrate metabolizing enzymes and other
      enzymes of the liver in diabetes is currently unknown. We therefore investigated
      changes in the activity levels of these enzymes following V. vinifera seed
      extract administration to diabetic rats. Methods. V. vinifera seed ethanolic
      extract (250 and 500 mg/kg/day) or glibenclamide (600 MUg/kg/day) was
      administered to streptozotocin-induced male diabetic rats for 28 consecutive
      days. At the end of treatment, liver was harvested and activity levels of various
      liver enzymes were determined. Levels of thiobarbituric acid reactive substances
      (TBARS) were measured in liver homogenates and liver histopathological changes
      were observed. Results. V. vinifera seed ethanolic extract was able to prevent
      the decrease in ICDH, SDH, MDH, and G-6-PDH and the increase in LDH activity
      levels in liver homogenates. The seed extract also caused serum levels of ALT,
      AST, ALP, ACP, GGT, and total bilirubin to decrease while causing total proteins
      to increase. Additionally, the levels of ALT, AST, and TBARS in liver homogenates
      were decreased. Histopathological changes in the liver were reduced. Conclusion.
      Near normal activity levels of various enzymes and histology of the liver
      following V. vinifera seed ethanolic extract administration may be due to
      decrease in liver oxidative stress in diabetes. 

PMID- 25852768
TI  - Multidetector CT with 3-dimensional volume rendering in the evaluation of the
      spine in patients with Neurofibromatosis type 1: a retrospective review in 73
      patients.
AB  - INTRODUCTION: Neurofibromatosis type 1 (NF-1) may involve the spine as various
      abnormalities including bony dysplasia, scoliosis, and nerve sheath tumors.
      Surgery may be performed for stabilization of the spine. We have seen an increase
      in requests for multidetector CT (MDCT) imaging with the (three-dimensional) 3D
      volume rendered (VR) images in patients evaluated at our institution. We,
      therefore, investigated how MDCT could be best utilized in this patient
      population. METHODS: Seventy-three patients with NF-1 were identified in whom
      MDCT imaging was performed for diagnostic, pre-operative, or post-operative
      evaluation of spinal abnormalities. True axial source images and two dimensional
      (2D) orthogonal reconstructed MDCT images, as well as the VR images, were
      compared with plain radiographs and MRI. In addition, the MDCT study was compared
      to the VR images. These studies were reviewed to compare assessment of A) bony
      abnormalities such as remodeling from dural ectasia, dysplasia, and fusion, B)
      abnormal spinal curvature, C) nerve sheath tumors, and D) surgical
      instrumentation. RESULTS: When compared to plain radiographs, the MDCT and VR
      images were rated as helpful for evaluating the abnormalities of the spine in 19
      of 24 patients for a total of 30 findings. This included the following categories
      A) (n = 6), B) (n = 5), C) (n = 7), and D) (n = 12). Compared to MR, the MDCT and
      VR study was helpful in evaluating the findings of NF-1 in 24 of 36 patients for
      a total of 40 findings. This included the following categories A) (n = 12), B) (n
      = 10), C) (n = 3), and D) (n = 15). When the VR images were compared to the
      orthogonal MDCT, the VR images was rated as helpful in 41 of 73 patients for a
      total of 60 findings, including the following categories: A) (n = 11), B) (n =
      24), C) (n = 0), and D) (n = 25). CONCLUSION: MDCT has distinct advantages over
      plain radiographs and MR imaging, and the VR images over MDCT in the evaluation
      of the spine in patients with NF-1, especially for the assessment of bony
      abnormalities, abnormal spinal curvature, and spinal instrumentation.

PMID- 25852769
TI  - Nutritional, chemical and microbiological changes during fermentation of tarhana
      formulated with different flours.
AB  - BACKGROUND: Tarhana is a fermented cereal product that is used for the
      preparation of one of the favourite soups in Turkish cuisine. Tarhana is a
      mixture of wheat flour, yoghurt, baker's yeast, salt, and various vegetables,
      spices and seasonings. It is obtained by mixing all ingredients in the recipe and
      afterwards the mixture is let to ferment at room temperature. Following
      fermentation tarhana is dried or frozen for long term storage. In this study, to
      improve the nutritional benefits of tarhana, whole wheat and chickpea flours were
      used as the sole source of flour. The changes in the phytic acid content,
      proteins and fermentation products were investigated in addition to some
      microbiological and chemical characteristics. RESULTS: The effect of flour type
      on the phytic acid content was significant. No differences were observed in the
      glutenin band patterns of the wheat and whole wheat flours and their tarhana
      samples. Conversely, for the gliadin fractions, the bands of the wheat and whole
      wheat flours were more intense than their tarhana samples. The changes in the
      glutelin and prolamin fractions of the chickpea flour and the resultant tarhana
      dough were similar to the glutenin and gliadin fractions of wheat and whole wheat
      flours and their tarhana samples. In all samples, the yeasts displayed an
      undulant growth pattern and the effect of flour type and fermentation time on
      yeast growth was significant (P < 0.01). The effect of flour type (P < 0.01) and
      fermentation time (P < 0.05) on mesophilic LAB was significant. Similar
      behaviours were observed with the mesophilic LAB in all samples and their numbers
      remained closed to their initial numbers. The growth of thermophilic LAB was not
      influenced by the flour type, but the effect of fermentation time was significant
      (P < 0.01). CONCLUSIONS: The whole wheat and chickpea tarhana are found to be
      good alternatives to classical tarhana with their higher nutritional benefits but
      further investigations are needed for the assessment of their sensory properties.

PMID- 25852770
TI  - The neurotoxic effects of ampicillin-associated gut bacterial imbalances compared
      to those of orally administered propionic acid in the etiology of persistent
      autistic features in rat pups: effects of various dietary regimens.
AB  - HYPOTHESIS: A healthy gut with normal intestinal microflora is completely
      disrupted by oral antibiotics. The byproducts of harmful gut bacteria can
      interfere with brain development and may contribute to autism. Strategies to
      improve the gut microflora profile through dietary modification may help to
      alleviate gut disorders in autistic patients. METHOD: Sixty young male western
      albino rats were divided into six equal groups. The first group served as the
      control; the second group was given an oral neurotoxic dose of propionic (PPA)
      (250 mg/kg body weight/day) for three days. The third group received an
      orogastric dose of ampicillin (50 mg/kg for three weeks) with a standard diet.
      Groups 4, 5 and 6 were given an orogastric dose of ampicillin and fed high
      carbohydrate, high-protein and high-lipid diets, respectively, for 10 weeks.
      Biochemical parameters related to oxidative stress were investigated in brain
      homogenates from each group. RESULT: The microbiology results revealed
      descriptive changes in the fecal microbiota of rats treated with ampicillin
      either alone or with the three dietary regimens. The results of PPA acid and
      ampicillin treatment showed significant increases in lipid peroxidation and
      catalase with decreases in glutathione and potassium compared with levels in the
      control group. A protein-rich diet was effective at restoring the glutathione
      level, while the carbohydrate-rich diet recovered lipid peroxidation and catalase
      activity. In addition, the three dietary regimens significantly increase the
      potassium level in the brain tissue of the test animals. Lactate dehydrogenase
      was remarkably elevated in all groups relative to the control. No outstanding
      effects were observed in glutathione S-transferase and creatine kinase.
      CONCLUSION: The changes observed in the measured parameters reflect the
      neurotoxic effects of PPA and ampicillin. Lipid peroxide and catalase activity
      and the levels of glutathione and potassium are satisfactory biomarkers of PPA
      and ampicillin neurotoxicity. Based on the effects of the three dietary regimens,
      a balanced diet can protect against PPA or ampicillin-induced neurotoxicity that
      might induce autistic traits. These outcomes will help efforts directed at
      controlling the prevalence of autism, a disorder that has recently been
      associated with PPA neurotoxicity.

PMID- 25852771
TI  - Establishing research priorities for patient safety in emergency medicine: a
      multidisciplinary consensus panel.
AB  - BACKGROUND: Patient safety in the context of emergency medicine is a relatively
      new field of study. To date, no broad research agenda for patient safety in
      emergency medicine has been established. The objective of this study was to
      establish patient safety-related research priorities for emergency medicine.
      These priorities would provide a foundation for high-quality research, important
      direction to both researchers and health-care funders, and an essential step in
      improving health-care safety and patient outcomes in the high-risk emergency
      department (ED) setting. METHODS: A four-phase consensus procedure with a
      multidisciplinary expert panel was organized to identify, assess, and agree on
      research priorities for patient safety in emergency medicine. The 19-member panel
      consisted of clinicians, administrators, and researchers from adult and pediatric
      emergency medicine, patient safety, pharmacy, and mental health; as well as
      representatives from patient safety organizations. In phase 1, we developed an
      initial list of potential research priorities by electronically surveying a
      purposeful and convenience sample of patient safety experts, ED clinicians,
      administrators, and researchers from across North America using contact lists
      from multiple organizations. We used simple content analysis to remove
      duplication and categorize the research priorities identified by survey
      respondents. Our expert panel reached consensus on a final list of research
      priorities through an in-person meeting (phase 3) and two rounds of a modified
      Delphi process (phases 2 and 4). RESULTS: After phases 1 and 2, 66 unique
      research priorities were identified for expert panel review. At the end of phase
      4, consensus was reached for 15 research priorities. These priorities represent
      four themes: (1) methods to identify patient safety issues (five priorities), (2)
      understanding human and environmental factors related to patient safety (four
      priorities), (3) the patient perspective (one priority), and (4) interventions
      for improving patient safety (five priorities). CONCLUSION: This study
      established expert, consensus-based research priorities for patient safety in
      emergency medicine. This framework could be used by researchers and health-care
      funders and represents an essential guiding step towards enhancing quality of
      care and patient safety in the ED.

PMID- 25852772
TI  - A pilot study to identify clinical predictors for wrist fractures in adult
      patients with acute wrist injury.
AB  - BACKGROUND: To date, no clinical decision rules for acute wrist injuries are
      available. In the past, clinical decision rules for the knee, ankle and spine
      injuries have been developed and validated. Implementation of these rules
      resulted in standardised clinical assessment at the emergency department and a
      substantial reduction of radiographic diagnostics. The objective of the study was
      to identify predictors for wrist fractures in patients with acute wrist injury
      which might potentiate a clinical decision rule in the future. This is a
      prospective pilot study in adult patients presenting with acute wrist injury at
      the emergency department of the Canisius-Wilhelmina Hospital in the Netherlands.
      METHODS: Clinical variables were collected in a case report file by emergency
      physicians. Radiography was ordered according to common practice to confirm or
      rule out the presence of fractures. Independent associations between the presence
      of clinical variables and wrist fractures were calculated. Multivariable analysis
      was performed in order to quantify sensitivity and specificity for fracture
      prediction. RESULTS: A total of 63 wrist fractures were detected in the study
      population of 95. Age over 55 years, inability to carry weight directly after
      trauma, support of injured wrist by the contralateral hand for pain relief,
      presence of swelling and/or hematoma, visible wrist deformity and reduced range
      of motion were associated with the presence of a wrist fracture. CONCLUSIONS: Our
      study identified clinical predictors for wrist fractures in patients with acute
      wrist injury. Future studies are needed for justification of evidence-based wrist
      assessment and identification of a 100% sensitive decision rule for wrist
      fractures.

PMID- 25852773
TI  - Radiologic diagnostic procedures in severely injured patients - is only whole
      body multislice computed tomography the answer?
AB  - BACKGROUND: Whole-body multislice computed tomography (WB-MSCT) has become an
      important diagnostic tool in the early treatment phase of severely injured
      patients. The optimal moment of WB-MSCT's use during this treatment phase remains
      unclear. Many trauma centers use WB-MSCT in addition to conventional radiographs,
      while some trauma centers use WB-MSCT as the only radiological tool. The aim of
      this study was to determine the differences between these two protocols and to
      answer the question of whether conventional radiographs can still be used in the
      safe treatment of polytrauma patients. METHODS: Patients from the TraumaRegister
      DGU(r) with an injury severity score (ISS) of >=16 were included. Group I
      received conventional radiographs and focused assessment with sonography in
      trauma (FAST) prior to a WB-MSCT, and group II received an initial WB-MSCT and
      FAST. Both groups were compared concerning treatment time and outcome. RESULTS: A
      total of 3,995 patients in group I were compared to 4,025 patients in group II.
      There were no differences in ISS (29.97 vs. 29.94), gender (male: 73.5% vs.
      72.8%), age (45.47 vs. 45.12 years), or calculated mortality (21.41% vs. 21.44%).
      Time needed in the resuscitation room was slightly longer in group I (72 vs. 64
      min); the durations until admittance to the ICU and arrival to the OR were not
      significantly different between the groups. There was no difference in mortality
      (18.2% vs. 18.4%) or the standardized mortality ratio (SMR) (0.85 vs. 0.86).
      CONCLUSIONS: WB-MSCT plays an inherent role in the treatment of multiple-injured
      patients. However, the use of WB-MSCT as the only diagnostic method in the
      resuscitation room is not needed. Conventional radiographs and FAST followed by
      WB-MSCT can be performed in the early resuscitation phase without impairing
      patient outcomes. This approach enables the emergency room team to perform life
      saving procedures - chest-tube insertion, laparotomy, cardiopulmonary
      resuscitation -immediately and simultaneous. Nevertheless, randomized multi
      center trials are needed to determine the comparability and effectiveness of
      these algorithms.

PMID- 25852774
TI  - A retrospective observational study of medical incident command and decision
      making in the 2011 Oslo bombing.
AB  - BACKGROUND: A core task for commanders in charge of an emergency response
      operation is to make decisions. The purposes of the study were to describe what
      critical decisions the ambulance commander and the medical commander make in a
      mass casualty incident response and to explore what the underlying conditions
      affecting decision-making are. The study was conducted in the context of the 2011
      government district terrorist bombing in Norway. METHODS: The study was a
      retrospective, descriptive observational study collecting data through
      participating observation, semi-structured interviews, and recordings of
      emergency medical services' radio communications. Analysis was conducted using
      systematic text condensation. The ambulance commander was interviewed using the
      critical decision method. RESULTS: The medical emergency response lasted 6.5 h,
      with little clinical activity after 2 h. Most critical decisions were made within
      the first 30 min, with the ambulance commander making the bulk of decisions.
      Situation assessment and underlying uncertainties strongly affected decision
      making, but there was a mutual interaction between these three factors that
      developed throughout the different stages of the operation. Knowledge and
      experience were major determinants of how easily commanders picked up sensory
      cues and translated them into situation assessments. The number and magnitude of
      uncertainties were largest in the development stage, after most of the critical
      decisions had been made. CONCLUSIONS: In the studied mass casualty incident, the
      commanders made most critical decisions in the early stages of the emergency
      response when resources did not meet demand. Decisions were made under
      significant uncertainty and time pressure. Ambulance and medical commanders
      should be prepared to make situation assessments and decisions early and be ready
      to adjust as uncertainties are reduced.

PMID- 25852775
TI  - 'Need-to-Know' emergency medicine articles of 2014.
AB  - Every year, thousands of articles are published in numerous medical journals that
      relate to the clinical practice of medicine. However, it is impossible for a
      single clinician to stay abreast of the literature, let alone to determine which
      articles should change daily practice. Physicians in our department have searched
      the emergency medicine and the specialty literature of 2014 to determine which
      articles are most relevant to the clinical practice of emergency medicine,
      summarized them, and listed key take-home points from these 'need-to-know'
      articles. 

PMID- 25852776
TI  - Multi-organ dysfunction secondary to severe wasp envenomation.
AB  - Wasp sting is not an uncommon incident. Around 56% to 94% of the population is
      stung at least once in their lifetime by a member of the order Hymenoptera which
      includes wasps, bees, and ants. The response to a wasp sting may vary from mild
      local reaction to severe systemic and anaphylactic reactions. The clinical
      picture and mortality rate tend to be more severe in adults compared to children.
      We present a 32-year-old agricultural worker who was bitten by multiple wasps
      while on a coconut tree. In spite of the heavy load of venom due to the multiple
      bites, the patient did not develop anaphylaxis. However, a delayed reaction did
      occur within 48 h in the form of severe multi-organ dysfunction. There was
      significant improvement by around 2 weeks; but it took another 6 months for the
      serum creatinine to normalize. This case highlights the occupational risk of
      Hymenoptera envenomation, the life-threatening complications that may follow and
      which may even be delayed as was the case with this patient, and the value of
      emergency care and intensive management which can result in a favorable clinical
      outcome. 

PMID- 25852777
TI  - Erratum: Emerging topics in FXTAS.
AB  - [This corrects the article DOI: 10.1186/1866-1955-6-31.]. 

PMID- 25852778
TI  - Improving N1 classification by grouping EEG trials with phases of pre-stimulus
      EEG oscillations.
AB  - A reactive brain-computer interface using electroencephalography (EEG) relies on
      the classification of evoked ERP responses. As the trial-to-trial variation is
      evitable in EEG signals, it is a challenge to capture the consistent
      classification features distribution. Clustering EEG trials with similar features
      and utilizing a specific classifier adjusted to each cluster can improve EEG
      classification. In this paper, instead of measuring the similarity of ERP
      features, the brain states during image stimuli presentation that evoked N1
      responses were used to group EEG trials. The correlation between momentary phases
      of pre-stimulus EEG oscillations and N1 amplitudes was analyzed. The results
      demonstrated that the phases of time-frequency points about 5.3 Hz and 0.3 s
      before the stimulus onset have significant effect on the ERP classification
      accuracy. Our findings revealed that N1 components in ERP fluctuated with
      momentary phases of EEG. We also further studied the influence of pre-stimulus
      momentary phases on classification of N1 features. Results showed that linear
      classifiers demonstrated outstanding classification performance when training and
      testing trials have close momentary phases. Therefore, this gave us a new
      direction to improve EEG classification by grouping EEG trials with similar pre
      stimulus phases and using each to train unit classifiers respectively. 

PMID- 25852779
TI  - Psychomotor functions at various weeks of chronic renal failure in rats.
AB  - In chronic renal failure there is a gradual retention of substances in the
      tissues and body fluids, called as uremic retention toxins, which can bring about
      a number of biochemical activities in the body. Chronic renal insufficiency also
      leads to progressive behavioural conflict. Uremic toxins can affect both the
      central and the peripheral nervous system. Uremic encephalopathy is also
      associated with problems in cognition and memory. To study the psychomotor
      functional disorders in rats with progressive chronic renal failure surgical
      nephrectomy was done by resection method. The animals were grouped into two
      control groups, Sham control (SC) and normal control (NC) and two uremic groups,
      moderate uremia (GM) and severe uremia (GS). Psychomotor analysis was done by
      passive avoidance and open field in these animals at 4, 8, 12, and 16 weeks.
      After the incubation period, the nephrectomised groups (GM and GS) showed
      significant changes in exploratory, locomotor and emotional behaviour when
      compared to the controls (NC and SC). Psychomotor changes involve poor cognition,
      reduced memory, reduced locomotor activity and decreased exploratory drive and
      emotional disturbance like increased fear during the initial stages. During the
      later stages a restless behaviour was noticed, associated with diminished fear. 

PMID- 25852780
TI  - Bifurcation dynamics and determination of alternate cell fates in bipotent
      progenitor cells.
AB  - The gene regulatory networks in which two lineage-affiliated transcription
      factors, such as GATA1 and PU.1, inhibit each other but activate themselves so as
      to regulate the choice between alternative cell fates have been extensively
      studied. These simple networks can generate bistability and explain the
      transitions between the alternative cell fates. The commitment of a progenitor
      cell to a new fate corresponds to the occurrence of different types of
      bifurcations, depending on if a system is symmetrical and how perturbations
      affect the system. Here we take a general modeling and analyzing approach and
      show that the lateral inhibition with symmetry and asymmetry can lead to
      different bifurcation dynamics. Especially, if cell fate decision-making is
      initiated with asymmetry or symmetry-breaking perturbations, a progenitor cell
      pre-patterns itself into a polarized cell, depending on the asymmetry or symmetry
      breaking perturbations. This study may help us understand the fundamental
      features of binary cell fate decisions more clearly and further apply to a wider
      range of decision-making processes. 

PMID- 25852781
TI  - EEG-based investigation of brain connectivity changes in psychotic patients
      undergoing the primitive expression form of dance therapy: a methodological pilot
      study.
AB  - Primitive expression (PE) is a form of dance therapy (DT) that involves an
      interaction of ethologically and socially based forms which are supplied for re
      enactment. There exist very few studies of DT applications including in their
      protocol the measurement of neurophysiological parameters. The present pilot
      study investigates the use of the correlation coefficient (rho) and mutual
      information (MI), and of novel measures extracted from rho and MI, on
      electroencephalographic (EEG) data recorded in patients with schizophrenia while
      they undergo PE DT, in order to expand the set of neurophysiology-based
      approaches for quantifying possible DT effects, using parameters that might
      provide insights about any potential brain connectivity changes in these patients
      during the PE DT process. Indication is provided for an acute potentiation
      effect, apparent at late-stage PE DT, on the inter-hemispheric connectivity in
      frontal areas, as well as for attenuation of the inter-hemispheric connectivity
      of left frontal and right central areas and for potentiation of the intra
      hemispheric connectivity of frontal and central areas, bilaterally, in the
      transition from early to late-stage PE DT. This pilot study indicates that by
      using EEG connectivity measures based on rho and MI, the set of useful
      neurophysiology-based approaches for quantifying possible DT effects is expanded.
      In the framework of the present study, the causes of the observed connectivity
      changes cannot be attributed with certainty to PE DT, but indications are
      provided that these measures may contribute to a detailed assessment of
      neurophysiological mechanisms possibly being affected by this therapeutic
      process. 

PMID- 25852782
TI  - An improved localization algorithm based on genetic algorithm in wireless sensor
      networks.
AB  - Wireless sensor network (WSN) are widely used in many applications. A WSN is a
      wireless decentralized structure network comprised of nodes, which autonomously
      set up a network. The node localization that is to be aware of position of the
      node in the network is an essential part of many sensor network operations and
      applications. The existing localization algorithms can be classified into two
      categories: range-based and range-free. The range-based localization algorithm
      has requirements on hardware, thus is expensive to be implemented in practice.
      The range-free localization algorithm reduces the hardware cost. Because of the
      hardware limitations of WSN devices, solutions in range-free localization are
      being pursued as a cost-effective alternative to more expensive range-based
      approaches. However, these techniques usually have higher localization error
      compared to the range-based algorithms. DV-Hop is a typical range-free
      localization algorithm utilizing hop-distance estimation. In this paper, we
      propose an improved DV-Hop algorithm based on genetic algorithm. Simulation
      results show that our proposed algorithm improves the localization accuracy
      compared with previous algorithms. 

PMID- 25852783
TI  - 3D DWT-DCT and Logistic MAP Based Robust Watermarking for Medical Volume Data.
AB  - Applying digital watermarking technique for the security protection of medical
      information systems is a hotspot of research in recent years. In this paper, we
      present a robust watermarking algorithm for medical volume data using 3D DWT-DCT
      and Logistic Map. After applying Logistic Map to enhance the security of
      watermarking, the visual feature vector of medical volume data is obtained using
      3D DWT-DCT. Combining the feature vector, the third party concept and Hash
      function, a zero-watermarking scheme can be achieved. The proposed algorithm can
      mitigate the illogicality between robustness and invisibility. The experiment
      results show that the proposed algorithm is robust to common and geometrical
      attacks. 

PMID- 25852784
TI  - Study on bayes discriminant analysis of EEG data.
AB  - OBJECTIVE: In this paper, we have done Bayes Discriminant analysis to EEG data of
      experiment objects which are recorded impersonally come up with a relatively
      accurate method used in feature extraction and classification decisions. METHODS:
      In accordance with the strength of alpha wave, the head electrodes are divided
      into four species. In use of part of 21 electrodes EEG data of 63 people, we have
      done Bayes Discriminant analysis to EEG data of six objects. Results In use of
      part of EEG data of 63 people, we have done Bayes Discriminant analysis, the
      electrode classification accuracy rates is 64.4%. CONCLUSIONS: Bayes Discriminant
      has higher prediction accuracy, EEG features (mainly alphawave) extract more
      accurate. Bayes Discriminant would be better applied to the feature extraction
      and classification decisions of EEG data.

PMID- 25852785
TI  - Ontological Security in Nursing Homes for Older Persons - Person-Centred Care is
      the Power of Balance.
AB  - INTRODUCTION: The Swedish national guidelines for elderly care describe how older
      persons should be able to trust that their care is permeated with security.
      Different theoretical perspectives can be found that describe what creates
      security. Many studies have been done about security. However, few studies have
      explicitly asked older persons what security in nursing homes means to them. AIM:
      The aim of the study was to describe how older persons in nursing homes talked
      and reflected about security in their daily lives. METHOD: Nine older persons
      were interviewed in, in-depth interviews one to three times and the resulting
      data was analysed using content analysis. RESULTS: The older persons adapted to
      having their own needs and those of the other older persons met and to the staff
      routines which created a sense of security. At the same time, they longed for
      security in which they could trust themselves and create their own daily life.
      Further to have a sense of belonging and of being liked for created an internal,
      interpersonal and external security. This can be linked to an ontological
      security which means having a sense of confidence in the continuity of self
      identity and order in events, a being in the world. CONCLUSION: Person-centred
      instead of institution- centred care can provide the balance of power that allows
      the older person to obtain ontological security in which the staff's ability to
      create a relationship with the older persons becomes crucial.

PMID- 25852786
TI  - Prevalence of latent tuberculosis infection and associated risk factors among
      1557 nursing students in a context of low endemicity.
AB  - INTRODUCTION: The risk of tuberculosis (TBC) in nurses is related to its
      incidence in the general population. Nursing students involved in clinical
      training could be exposed to occupational risks similar to those of healthcare
      workers (HCWs). To better understand the epidemiology of nosocomial TBC among
      nurses in a context of low endemicity, we recruited a cohort of young nursing
      trainees at the Second University of Naples. METHODS: A screening programme for
      LTBI in nursing students was conducted between January 2012 and December 2013, at
      the Second University of Naples, with clinical evaluations, tuberculin skin test
      (TST) and, in positive TST student, the interferon-g release assays (IGRA).
      Putative risk factors for LTBI were assessed by a standardized questionnaire.
      RESULTS: 1577 nursing students attending the Second University of Naples have
      been submitted to screening programme for TBC. 1575 have performed TST as first
      level test and 2 Quantiferon test (QFT). 19 students were TST positive and
      continued the diagnostic workup practicing QFT, that was positive in 1 student.
      Of the 2 subjects that have practiced QFT as first level test only 1 was
      positive. In 2 students positive to QFT test we formulated the diagnosis of LTBI
      by clinical and radiographic results. CONCLUSION: The prevalence of LTBI among
      nursing students in our study resulted very low. In countries with a low
      incidence of TBC, the screening programs of healthcare students can be useful for
      the early identification and treatment of the sporadic cases of LTBI.

PMID- 25852787
TI  - Omental pregnancy: case report and review of literature.
AB  - Pregnancy, the implantation of a fertilized ovum outside the endometrial cavity,
      occurs in 1.5%-2% of pregnancies. It is one of the major causes (about 6%) of
      maternal death during the first trimester of pregnancy. The remaining 5% implant
      in the ovary, peritoneal cavity, within the cervix, and the omental pregnancy is
      the least common form of abdominal pregnancies. A review of the literature on
      Medline for the period 1958-2012 reported only 16 cases of omental pregnancy.
      Here we report a case of primary omental pregnancy in a nulliparous woman. A 24
      year-old woman gravid 1, para 0, with lower abdominal pain. Her last menstrual
      period occurred 8 weeks before the visit. The physical examination revealed
      abdominal tenderness in the lower quadrants, she was not bleeding. Transvaginal
      ultrasound showed: a free anechoic/hypoechoic area of 30 x 57 mm in the pouch of
      Douglas and the endometrium was homogeneus with a thickness of 12 mm and no
      evidence of gestational sac in the uterine cavity. Laboratory data revealed a
      normal cell blood count and beta hcg levels of 8047 IU / L. Because of continuing
      abdominal pain and a diagnosis of ectopic pregnancy a diagnostic laparoscopy was
      performed, which showed hemoperitoneum. Further inspection of abdominal cavity
      revealed a bloody lesion that was tenaciously adherent to the omentum, using non
      traumatic laparoscopic forceps and bipolar scissors we carefully removed a
      friable mass of about 30 mm from the omental attachments. Histological
      examination showed the presence of blood clot material mixed with trophoblastic
      tissue. Ultrasound evaluation and and hCG assessment are important to determine
      the extrauterine location of the ectopic pregnancy but the early diagnosis of
      abdominal pregnancy requires also a laparoscopic evaluation and, as our case has
      highlighted, thorough abdominal exploration especially in the absence of adnexal
      findings when ectopic pregnancy is highly suspected. Early diagnosis of omental
      pregnancy is difficult but essential to reduce the high mortality risk for the
      mother. 

PMID- 25852788
TI  - [Management of cervical cancer during pregnancy: report of 05 cases].

PMID- 25852789
TI  - Management of a rare case of arrhythmogenic right ventricular dysplasia in
      pregnancy: a case report.
AB  - Arrhythmogenic right ventricular dysplasia is a rare but not exceptional
      inherited cardiomyopathy characterized by fibrofatty replacement of the
      myocardium of the right ventricular which could lead to serious arrhythmia and
      sudden death. Only a few cases of pregnancies with ARVD have been reported. The
      aim of this case presentation is to describe the clinical characteristics and
      anesthetics specificities in management of this disease in pregnancy and in
      delivery. We report the case of a young woman aged 28 years old with a past
      history of ARVD treated by medical treatment with radiofrequency ablation. This
      patient was pregnant and it was scheduled for cesarean section delivery.
      Preoperative evaluation showed a well tolerated pregnancy inspite of the severity
      of the ARVD. It was a severe form of ARVD because of RV dilation, the spread of
      the disease to LV and the history of ventricular tachycardia during an attempted
      of ablation by radio frequency. The treatment received by the patient was kept
      until the day of surgery. The act took place under general anesthesia. The
      postoperative period was uneventful and morphine titration was used for pain
      relief. The patient exits the hospital 3 days after delivery and breastfeeding
      was forbidden. We should pay attention on this disease witch is not yet well
      known and witch is highly risky in the peri-partum period. Even if pregnancy may
      be tolerated in moderate forms of ARVD, conception and delivery sould be
      discouraged especially in severe forms. 

PMID- 25852790
TI  - [A neuroleptic malignant syndrome complicated by subarachnoid hemorrhage and
      revealing cerebral vasculitis].

PMID- 25852791
TI  - [Sero-epidemiological study of canine leishmaniasis in central Morocco].

PMID- 25852792
TI  - [Pure tibiotalar dislocation: about a case with review of the literature].

PMID- 25852793
TI  - [General medicine perceived by the students of the Faculty of Medicine of Sousse
      (Tunisia)].

PMID- 25852794
TI  - An unusual manifestation of hyperkalemia.

PMID- 25852795
TI  - [A saccular aneurysm of the abdominal aorta revealing Behcet disease: when to
      operate?].

PMID- 25852796
TI  - Menstrual hygiene management amongst schoolgirls in the Rukungiri district of
      Uganda and the impact on their education: a cross-sectional study.
AB  - INTRODUCTION: An increasing number of studies have found that girls in low-income
      settings miss or struggle at school during menstruation if they are unable to
      manage their menstrual hygiene effectively. This study explores the menstrual
      hygiene practices and knowledge of girls at rural government primary schools in
      the Rukungiri district in Uganda and assesses the extent to which poor menstrual
      hygiene management (MHM) affects their education. METHODS: A self-administered
      questionnaire was completed by schoolgirls in six government-run primary schools
      in the Rukungiri district. Focus groups were held with girls from each school and
      semi-structured interviews were conducted with headteachers and female teachers
      from the participating schools. A toilet assessment was also conducted in each
      school. RESULTS: One hundred and forty schoolgirls completed the questionnaire.
      The girls reported a lack of access to adequate resources, facilities and
      accurate information to manage their menstrual hygiene effectively at school.
      They reported that, as a result, during menstruation they often struggle at
      school or miss school. Eighty-six girls (61.7%) reported missing school each
      month for menstrual-related reasons (mean 1.64, range 0-10, SD. 1.84).
      CONCLUSION: It is common for girls who attend government-run primary schools in
      the Rukungiri district to miss school or struggle in lessons during menstruation
      because they do not have access to the resources, facilities, or information they
      need to manage for effective MHM. This is likely to have detrimental effects on
      their education and future prospects. A large-scale study is needed to explore
      the extent of this issue.

PMID- 25852797
TI  - Severe Klippel-Feil syndrome with Mondini malformation of inner ear.
AB  - Klippel-Feil syndrome is defined as the fusion of cervical vertebra with
      associated congenital anomalies but was rarely reported to be associated with
      Mondini Malformation. We report a newborn girl with severe neck extension,
      computed tomography (CT) of the neck after birth showed fusion of the fifth,
      sixth, and seventh cervical vertebrae, compatible with Klippel-Feil Syndrome and
      CT temporal bone showed choclear dysplasia with incomplete number of turns that
      is compatible with Mondini Malformation. 

PMID- 25852798
TI  - Knowledge and practices towards rabies and determinants of dog rabies vaccination
      in households: a cross sectional study in an area with high dog bite incidents in
      Kakamega County, Kenya, 2013.
AB  - INTRODUCTION: An estimated 55,000 people die from rabies annually. Factors
      promoting dog vaccination, estimates of vaccination coverage and knowledge on
      rabies are important for effective rabies control. We sought to establish these
      estimates at household (HH) level and whether rabies knowledge is associated with
      proper control practices. METHODS: Cross-sectional cluster survey with two-stage
      sampling was employed in Kakamega County to enroll HH members above 18 years. A
      set of questions related to rabies knowledge and practice were used to score
      participant response. Score above the sample mean was equated to adequate
      knowledge and proper practices respectively. Independent t-test was used to
      evaluate the differences of sample mean scores based on dog vaccination status.
      Bivariate analysis was used to associate knowledge to practices. RESULTS: Three
      hundred and ninety HHs enrolled and had a population of 754 dogs with 35% (n =
      119) HH having vaccinated dogs within past 12 months. Overall mean score for
      knowledge was 7.0 (+/-2.8) with range (0-11) and 6.3 (+/-1.2) for practice with
      range (0-8). There was a statistically significant difference in mean knowledge
      (DF = 288, p < 0.01) and practice (DF = 283, p = 0.001) of HH with vaccinated
      dogs compared to ones with unvaccinated dogs. Participants with adequate rabies
      knowledge were more likely to have proper health seeking practices 139 (80%) (OR
      = 3.0, 95% CI = 1.4-6.8) and proper handling practices of suspected rabid dog 327
      (88%) (OR = 5.4, 95% CI = 2.7-10.6). CONCLUSION: Rabies vaccination below the 80%
      recommended for herd immunity. Mass vaccination campaign needed. More innovative
      ways of translating knowledge into proper rabies control practice are warranted.

PMID- 25852799
TI  - Collateral benefits arising from mass administration of azithromycin in the
      control of active trachoma in resource limited settings.
AB  - INTRODUCTION: The benefits of the use of antibiotics in the mass treatment for
      active trachoma and other diseases have been documented, but the secondary
      effects arising from such a programme have not been fully elucidated. The purpose
      of this study was to investigate the potential secondary benefits arising from
      the use of azithromycin in mass treatment of active trachoma in an economically
      challenged Kenyan nomadic community. METHODS: Health information reports for
      January 2005 to December 2010 were reviewed to determine the annual trends of
      infectious diseases in the two districts, Narok and Transmara. The year 2007 was
      considered as the baseline for mass drug administration (MDA). Odds ratios (OR)
      were used to describe the association. RESULTS: The mass distribution coverage in
      Narok was 83% in 2008, 74% in 2009 and 63% in 2010. The odds for malaria (OR =
      1.13; 95% CI 1.12-1.14), diarrhoeal diseases (OR = 1.04; 95% CI 1.01-1.06),
      urinary tract infections (UTIs) (OR = 1.21; 95% CI 1.17-1.26), intestinal worms
      (OR, 4.98; 95% CI 4.68-5.3), and respiratory diseases other than pneumonia (OR,
      1.15; 95% CI 1.13-1.16) were higher after three rounds of mass treatment,
      indicating a better outcome. Before the intervention, there was a reducing trend
      in the odds for respiratory diseases. In Transmara (control), there was an
      increase in odds for malaria, respiratory infections, UTIs and intestinal worms.
      The odds for diarrhoeal diseases, skin diseases and pneumonia decreased
      throughout the study period. CONCLUSION: Mass distribution of azithromycin may
      have contributed to the decrease in the prevalence of the respiratory infections
      in Narok District.

PMID- 25852800
TI  - Comparative functional exercise capacity of patients with type 2-diabetes and
      healthy controls: a case control study.
AB  - INTRODUCTION: Functional Exercise Capacity (FEC) is a valid measure of physical
      fitness in health and disease. However, there is paucity of studies on FEC in
      African patients with Type-2 Diabetes (T2D). This study compared FEC between
      patients with T2D and healthy controls. METHODS: Thirty five patients with T2D
      (18 men, 17 women) and 35 (16 men, 19 women) age-sex matched healthy controls
      participated in this case-control study. Anthropometric and demographic
      characteristics and cardiovascular parameters were measured following standard
      procedures. A glucometer was used to determine the Fasting Blood Glucose (FBG)
      level following at least 8 hours of overnight fasting. FEC was assessed using the
      Six-Minute Walk Test (6MWT) while Hand Grip Strength (HGS) test was measured with
      an electronic dynamometer. Data were analyzed using descriptive and inferential
      statistics. Alpha level was set at p< 0.05. RESULTS: Patients with T2D and
      controls were similar in age (p > 0.05). There were significant differences in
      the distance covered during 6MWT between patients and controls (t= 0.329; p
      =0.03), exercise capacity (t = 0.329; p = 0.03), FBG (t = 7.403; p = 0.001),
      systolic and diastolic blood pressure (t = 12.56; p = 0.001 and t = 27.23; p =
      0.001) respectively. There were significant inverse relationships between 6MWD
      and Body mass index (r = -0.39; p = 0.02) and FBS(r = -0.51; p = 0.02) in
      patients with type-2 respectively. No significant association was found between
      exercise capacity and HGS (p > 0.05). CONCLUSION: Patients with type-2 diabetes
      demonstrated lower functional exercise capacity than healthy controls. High body
      mass index and fasting blood glucose were significantly associated with lower
      functional exercise capacity.

PMID- 25852801
TI  - [Hoffa ligament ossification: final evolution of the Hoffa disease (about a case
      with review of the literature)].

PMID- 25852802
TI  - Awareness, treatment, control of hypertension and utilization of health care
      services following screening in the North-central region of Burkina Faso.
AB  - INTRODUCTION: In Africa, a non-urban area is affected by hypertension. But in
      Burkina Faso, no study on factors associated with awareness, treatment and
      control of hypertension has not yet been published. The objectives of this report
      are to: (i) identify the factors associated with awareness, treatment, and
      control of hypertension in the adult population of Kaya health and demographic
      surveillance system (Kaya HDSS) and (ii) estimate health care services
      utilization by participant newly screened as hypertensive. METHODS: A screening
      survey for hypertension was conducted on 1481 adults in Kaya HDSS in late 2012.
      Hypertensive individuals provided information relating to "awareness",
      "treatment" and "control" of their hypertension. After approximately two months,
      unaware hypertensive individuals were interviewed to know whether they had sought
      treatment. RESULTS: During the screening survey, 123 individuals (9.4%) were
      identified as having hypertension. Among them, 33 (26.8%, 95% CI: 18.9-34.8) were
      aware of their condition, 25 (75.8%, 95% CI: 60.3-91.2) of them were receiving
      medication. Among those receiving treatment, 15 (60.0%, 95% CI: 39.4-80.6) had
      their blood pressure controlled. Semi-urban residence, presence of chronic
      diseases and physical inactivity were significantly associated with awareness of
      hypertension. Seventy two of the 90 participants who were classified as unaware
      were interviewed two months later. Out of them, 37 individuals had consulted a
      health worker and 28 received a diagnosis of hypertension. CONCLUSION: Awareness
      was low but treatment and control of those who knew they were hypertensive were
      relatively high. These results could be used to improve management of
      hypertension in Burkina Faso.

PMID- 25852803
TI  - [Epidemiological, clinical and etiological chest pain in outpatient cardiology
      consultations Ouagadougou].

PMID- 25852804
TI  - Correlates for cardiovascular diseases among diabetic/hypertensive patients
      attending outreach clinics in two Nairobi slums, Kenya.
AB  - INTRODUCTION: Cardiovascular diseases (CVD) are the leading cause of death in the
      world. Over 80% of CVD related deaths occur in low- and middle-income countries
      (LMICs). Diabetes and hypertension, whose prevalence in Kenya is on the rise, are
      major risk factors for CVD. Despite this, studies indicate that awareness on the
      management of risk factors for CVD among diabetic/hypertensive patients in
      African populations is generally low. The aim of the study was to determine the
      risk factors for CVD among diabetic and/or hypertensive patients attending
      diabetes and hypertension management clinics in Korogocho and Viwandani slums of
      Nairobi. METHODS: Data were collected using questionnaires administered to 206
      diabetic/hypertensive patients attending the clinics between July 2010 and
      February 2011. A review of these patients' medical records was done to determine
      the history of CVD outcomes such as hypertensive heart diseases, stroke and
      peripheral arterial diseases. RESULTS: Majority (66.5%) of the study participants
      were females mainly in the 51-65 age category. The study findings revealed that
      73 (33.4%) respondents had CVD outcomes. In addition, 41.8% of the respondents
      were not aware of the causes of diabetes/hypertension. Age category 51-65 years
      had the highest (43.8%) number of respondents with CVD. Sex of the respondents
      and awareness of the link between hypertension and CVD were significantly
      associated with CVD outcomes (p<0.05) among the respondents. CONCLUSION: Measures
      to improve awareness levels among patients at high risk of CVD outcomes are
      needed to complement other measures to reduce CVD risk among such patients.

PMID- 25852805
TI  - [Upper gastrointestinal endoscopy in 2795 patients at the university campus
      hospital of Lome: peculiarities according to sex].

PMID- 25852806
TI  - Acceptance of temporal artery thermometry by Nigerian mothers: a comparison with
      the traditional methods.
AB  - INTRODUCTION: Temporal artery thermometry may be viewed as a suitable alternative
      to the traditional thermometry because of its safety and time efficiency.
      However, it is yet to gain wide acceptance in African settings because it is
      relatively new. The aim of this study was to compare the choices of Nigerian
      mothers between the traditional methods (axillary and rectal thermometry) and the
      temporal artery thermometry. METHODS: Rectal, axillary and forehead temperatures
      were measured in 113 children using rectal and axillary mercury in glass
      thermometers and infrared temporal artery thermometer respectively. The
      thermometry method preferred by each mother and the reason(s) were documented
      using a semi structured questionnaire. The data was analysed using SPSS version
      19. RESULTS: The highest number of mothers 44(38.9%) preferred the axillary route
      while 42(37.2%) and 27(23.9%) preferred the temporal and rectal routes
      respectively. Temporal artery thermometry was the most popular among the mothers
      with tertiary education 27(39.7%), whereas axillary thermometry was most
      preferred among mothers with primary and secondary education, although this
      difference was not statistically significant (chi(2)=0.62,p = 0.96). Mothers
      27(33.9%) who preferred rectal thermometry did so because they felt that since
      the thermometer is inserted inside the body, it will detect fever better.
      CONCLUSION: Nigerian mothers do not have any particular thermometry preference
      between the temporal artery thermometry and the traditional methods, so medical
      personnel in our environment may resort to any method that is convenient,
      accurate, fast and cost effective.

PMID- 25852807
TI  - Screening of fetal alcohol syndrome using the T-ACE questionnaire in semi-rural
      areas around Lubumbashi: lessons learned.

PMID- 25852808
TI  - The assessment of job satisfaction for the healthcare providers in university
      clinics of Lubumbashi, Democratic Republic of Congo.
AB  - INTRODUCTION: In the world, the health policies are necessary to satisfy with
      efficiency the requirements of the quality management in the health sector. The
      laboratory of the academic clinics of Lubumbashi in Africa was inspired by the
      EFQM model to improve its performance and the quality of its services offered to
      the community. The aim of this survey is to evaluate the level of job
      satisfaction of the healthcare providers after implementation of the model.
      METHODS: Qualitative study used an anonymous questionnaire consisted of 16 semi
      directional dichotomous and 12 according to four modality of the Likert's scale;
      to evaluate the job satisfaction of the healthcare providers. 40 workers are
      concerned and their informed consent is obtained. Epi Info 3.5.3 and SPSS 19.0
      software, the Student t test and Chi-square test and the threshold set at p <=
      0.05 were used. The mean score was calculated. Cronbach's ' coefficient and
      principal component analysis allowed the validity measurement of the
      questionnaire, and the correlations has been calculated. RESULTS: This survey had
      a rate of answer of 80% on a set of all questionnaires. The Cronbach's
      coefficient of reliability is 0.72 on 40 complete observations with 12 questions.
      The Kaiser Meyer Olkin (0.564) and the Bartlett test is significant (chi(2)= 57,
      30, p=0.001). The Physicians are very dissatisfied (2.363) against the nurses,
      and the biologists who are moderately dissatisfied (3 and 3.312). The relative
      results to the global satisfaction of the workers show a meaningful difference
      between the workers satisfied versus those non satisfied (p = 0.003). More of the
      half of the workers is satisfied after the setting up of the EFQM model.
      CONCLUSION: A certain number of the factors act together and simultaneously on
      the satisfaction of the workers particular in the health sector. The EFQM model
      permits the job satisfaction in the hospital because it combines several factors
      acting on the individuals.

PMID- 25852809
TI  - Yearly Burden of Skin Cancer in Non-Caucasian and Caucasian Solid-organ
      Transplant Recipients.
AB  - OBJECTIVE: To examine the skin cancer tumor accrual rates in non-Caucasian and
      Caucasian post-transplant recipients. DESIGN/SETTING/PARTICIPANTS: Retrospective
      chart review of solid-organ transplant patients who presented to the outpatient
      dermatology clinic at the University of Chicago and have had at least one skin
      biopsy to rule in/out skin cancer in the 10-year period from January 1, 2003, to
      December 31, 2012. One hundred fifty-two solid-organ transplant recipients were
      identified through a natural language search in CoPathPlus. MEASUREMENTS: Each
      transplant patient's skin cancer accrual rates, defined as the number of skin
      cancers per person per year, were examined. The average accrual rates for non
      Caucasians and Caucasians were compared and analyzed. RESULTS: Of the 152 post
      transplant patients identified, 58 were non-Caucasian and 94 were Caucasian.
      Eight (13.8%) non-Caucasians developed skin cancer, compared to 61 (64.9%)
      Caucasians (P< 0.001). Non-Caucasian post-transplant patients had lower skin
      cancer accrual rates with an overall skin cancer accrual rate of 0.13, squamous
      cell carcinoma accrual rate of 0.10, and basal cell carcinoma accrual rate of
      0.01 versus 1.13 (P< 0.001), 0.96 (P< 0.001), and 0.15 (P< 0.001), respectively,
      for Caucasian patients. Comparison of post-transplant non-Caucasian and Caucasian
      patients who developed skin cancer revealed lower overall (0.96 vs. 1.74;
      P=0.25), squamous cell carcinoma (0.75 vs. 1.49; P=0.16), and basal cell
      carcinoma (0.06 vs. 0.24; P=0.13) accrual rates in non-Caucasians. CONCLUSION:
      The authors' findings highlight the importance of annual total body skin exams
      for post-transplant patients and the need to identify and further educate those
      transplant patients with a higher risk for skin cancer development.

PMID- 25852810
TI  - Negative predictive value of pigmented lesion evaluation by multispectral digital
      skin lesion analysis in a community practice setting.
AB  - OBJECTIVE: To determine if the high negative predictive value of a multispectral
      digital skin lesion analysis that has been previously found in an academic-based
      trial would be similar in a community-based setting with its expected different
      distribution of pigmented lesions. DESIGN: Data were collected from patients
      undergoing routine skin examinations over a one-year period at a community-based
      practice in Florida. All lesions that were selected for biopsy to rule out
      melanoma were also imaged with multispectral digital skin lesion analysis prior
      to biopsy. Histopathological diagnoses and multispectral digital skin lesion
      analysis results were reviewed and compared with findings from a prior primarily
      academic center-based multispectral digital skin lesion analysis trial.
      SETTING/PARTICIPANTS: Community-based clinical setting in Florida. MEASUREMENTS:
      Negative predictive value, sensitivity, and specificity. RESULTS: One hundred
      thirty-seven consecutive lesions were selected for biopsy and also analyzed via
      multispectral digital skin lesion analysis. All 21 cases with multispectral
      digital skin lesion analysis "Low Disorganization" readings were all
      histologically benign (100% negative predictive value, 95% lower confidence
      boundary = 96.9%). The negative predictive value and the sensitivity were not
      significantly different than what was found in the prior academic-based
      multispectral digital skin lesion analysis trial. Multispectral digital skin
      lesion analysis also correctly identified all high-risk lesions, which were
      subsequently confirmed via histology to be one invasive melanoma and 15
      moderately dysplastic nevi (100% sensitivity). Specificity with multispectral
      digital skin lesion analysis was significantly higher than reported in the
      academic-based multispectral digital skin lesion analysis trial (18% vs. 10%,
      p=0.02). CONCLUSION: Because of the high negative predictive value achieved by
      multispectral digital skin lesion analysis, lesions with readings of "Low
      Disorganization" may be considered for observation versus biopsy. Similar to what
      was noted in the academic center setting, multispectral digital skin lesion
      analysis may help dermatologists reduce the number of unnecessary biopsies while
      improving diagnostic accuracy.

PMID- 25852811
TI  - Tanning Bed Perception Survey: A Questionnaire-based Study.
AB  - OBJECTIVE: This study was intended to investigate the perception of tanning bed
      use among college students. DESIGN: A 15-question survey was given to young
      adults regarding tanning perceptions. SETTING: Rochester Community College in
      Rochester, Minnesota. PARTICIPANTS: Forty-four respondents between 18 and 51
      years of age. MEASUREMENTS: Data was collected via a self-reported questionnaire.
      RESULTS: In this study, 50 percent of participants were not educated on the risks
      of melanoma, and 68 percent were not interested in receiving information on
      melanoma and completing a follow-up survey. More specifically, 63 percent versus
      89 percent of participants with no tanning bed versus some tanning bed use did
      not want information regarding melanoma, respectively. This study also shows that
      more tanning bed users believe tanning helps prevent burning than non-tanning bed
      users. Fifty-seven percent of the 35 participants who had never used a tanning
      bed thought that they never prevent sunburn, while only 11 percent of the nine
      participants who had used a tanning bed in the past thought that they never
      prevent sunburn, which was statistically significant.

PMID- 25852812
TI  - Treatment of Age-related Mid-face Atrophy by Injection of Cohesive Polydensified
      Matrix Hyaluronic Acid Volumizer.
AB  - OBJECTIVE: Cohesive Polydensified Matrix(r) Hyaluronic Acid Volumizer is designed
      to be injected subcutaneously or in deeper soft tissue layers to restore facial
      volumes. This post-marketing clinical follow-up was performed to confirm the
      safety and effectiveness of the product up to 18 months. DESIGN: Injections were
      performed according to standard clinical practice and patients were followed-up
      at Months 1, 3, 6, 9, 12, and optionally at Month 18. Effectiveness measures
      included facial volume loss scale, global aesthetic improvement scale and
      patients' satisfaction. Injection site reactions were recorded to evaluate
      safety. RESULTS: Twenty patients with intermediate-to-severe volume loss in the
      lateral cheek hollows and/or cheekbone area were treated. Facial volume loss
      scale scores dropped significantly from a mean value of 3.1 at baseline to 1.3 at
      Day 1. Significant volume enhancement was maintained at each follow-up visit with
      mean scores ranging from 1.3 at Month 1 to 1.8 at Month 12. Investigators' global
      aesthetic improvement scale assessment showed that up to Month 6 at least 94
      percent of patients were rated as "very much improved" or "much improved." At
      Month 9, all patients still showed a benefit of treatment with 81 percent rated
      as "very much" or "much improved" and 19 percent as "improved." Patients'
      evaluation was consistent with investigators' results. A few expected transient
      injection site reactions of mild-to-moderate intensity were reported immediately
      after treatment. These reactions were considered related to the injection
      procedure, rather than the product. CONCLUSION: Cohesive Polydensified Matrix
      Hyaluronic Acid Volumizer is safe and effective for mid-face volume augmentation
      lasting up to Month 12 and most probably up to Month 18. The aesthetic effect was
      demonstrated by the effectiveness evaluations and high patient satisfaction.

PMID- 25852813
TI  - Scalp micropigmentation: a concealer for hair and scalp deformities.
AB  - BACKGROUND: Cosmetic deformities, resulting from some dermatologic diseases or
      deformities caused by hair restoration surgeries, have had few, if any, good,
      permanent solutions. Most of these patients have learned to live with their
      problems. OBJECTIVE: A cosmetic tattoo technique has been developed to address
      unsightly scalp and hair conditions. MATERIALS AND METHODS: The technique called
      scalp micropigmentation uses specialized techniques and conventional cosmetic
      tattoo instruments and pigments in a stippling pattern on the scalp. RESULTS: A
      variety of alopecias, refractory to treatment and hair transplant deformities,
      impact millions of men and women. Many of these deformities can be concealed with
      scalp micropigmentation, making the deformities minimally detectable. Included
      are the results of treatment. Patient satisfaction is very high. CONCLUSION:
      Scalp micropigmentation offers a good nonsurgical alternative treatment for hair
      and scalp deformities. This paper demonstrates scalp micropigmentation results
      and discusses the histology, physiology, and pathology of tattoo pigments in the
      skin. The regulation of the tattoo process by the United States Food and Drug
      Administration and state governments is summarized. Unlike medical devices, scalp
      micropigmentation offers a tattoo-based, non-medical "cover-up" that effectively
      hides unsightly conditions on the scalp and creates the illusion of thicker hair.
      The authors believe that scalp micropigmentation is destined to become a
      standardized offering for physicians specializing in cosmetic office procedures.

PMID- 25852814
TI  - Nonalcoholic Fatty liver disease and psoriasis: what a dermatologist needs to
      know.
AB  - Psoriasis is a systemic inflammatory disease associated with a variety of
      comorbidities. It has been shown that psoriasis patients have an increased
      incidence of nonalcoholic fatty liver disease over controls. Patients with
      nonalcoholic fatty liver disease and psoriasis have more severe skin disease and
      are at higher risk of severe liver fibrosis than patients without psoriasis. The
      authors will review the diagnosis of nonalcoholic fatty liver disease and also
      discuss lifestyle changes and treatments for psoriasis that may benefit or worsen
      nonalcoholic fatty liver disease. 

PMID- 25852815
TI  - Phototherapy-induced Purpuric Eruption in a Neonate.
AB  - Phototherapy is commonly utilized in the treatment of neonatal jaundice. The
      authors observed a rare cutaneous complication of visible blue light phototherapy
      in a neonate with hyperbilirubinemia. A three-day-old neonate was evaluated for a
      purpuric rash after initiation of phototherapy for treatment of
      hyperbilirubinemia. Cutaneous examination revealed purpuric, nonblanching, well
      demarcated lesions on the chest, abdomen, arms, and chin with sparing at shielded
      sites. The history, physical examination, and laboratory results support the
      diagnosis of purpuric phototherapy-induced eruption. The authors present a case
      report of this uncommon cutaneous eruption in a transfused neonate undergoing
      phototherapy for treatment of hemolytic disease of the newborn. 

PMID- 25852817
TI  - Hallmarks of epithelial to mesenchymal transition are detectable in Crohn's
      disease associated intestinal fibrosis.
AB  - BACKGROUND: Intestinal fibrosis and subsequent stricture formation represent
      frequent complications of Crohn's disease (CD). In many organs, fibrosis develops
      as a result of epithelial to mesenchymal transition (EMT). Recent studies
      suggested that EMT could be involved in intestinal fibrosis as a result of
      chronic inflammation. Here, we investigated whether EMT might be involved in
      stricture formation in CD patients. METHODS: Human colonic tissue specimens from
      fibrotic areas of 18 CD and 10 non-IBD control patients were studied.
      Immunohistochemical staining of CD68 (marker for monocytes/macrophages),
      transforming growth factor-beta1 (TGFbeta1), beta-catenin, SLUG, E-.cadherin,
      alpha-smooth muscle actin and fibroblast activation protein (FAP) were performed
      using standard techniques. RESULTS: In fibrotic areas in the intestine of CD
      patients, a large number of CD68-positive mononuclear cells was detectable
      suggesting an inflammatory character of the fibrosis. We found stronger
      expression of TGFbeta1, the most powerful driving force for EMT, in and around
      the fibrotic lesions of CD patients than in non-IBD control patients. In CD
      patients membrane staining of beta-catenin was generally weaker than in control
      patients and more cells featured nuclear staining indicating transcriptionally
      active beta-catenin, in fibrotic areas. In these regions we also detected nuclear
      localisation of the transcription factor, SLUG, which has also been implicated in
      EMT pathogenesis. Adjacent to the fibrotic tissue regions, we observed high
      levels of FAP, a marker of reactive fibroblasts. CONCLUSIONS: We demonstrate the
      presence of EMT-associated molecules in fibrotic lesions of CD patients. These
      findings support the hypothesis that EMT might play a role for the development of
      CD-associated intestinal fibrosis.

PMID- 25852816
TI  - Intracellular oxidant activity, antioxidant enzyme defense system, and cell
      senescence in fibroblasts with trisomy 21.
AB  - Down's syndrome (DS) is characterized by a complex phenotype associated with
      chronic oxidative stress and mitochondrial dysfunction. Overexpression of genes
      on chromosome-21 is thought to underlie the pathogenesis of the major phenotypic
      features of DS, such as premature aging. Using cultured fibroblasts with trisomy
      21 (T21F), this study aimed to ascertain whether an imbalance exists in
      activities, mRNA, and protein expression of the antioxidant enzymes SOD1, SOD2,
      glutathione-peroxidase, and catalase during the cell replication process in
      vitro. T21F had high SOD1 expression and activity which led to an interenzymatic
      imbalance in the antioxidant defense system, accentuated with replicative
      senescence. Intracellular ROS production and oxidized protein levels were
      significantly higher in T21F compared with control cells; furthermore, a
      significant decline in intracellular ATP content was detected in T21F. Cell
      senescence was found to appear prematurely in DS cells as shown by SA-beta-Gal
      assay and p21 assessment, though not apoptosis, as neither p53 nor the
      proapoptotic proteins cytochrome c and caspase 9 were altered in T21F. These
      novel findings would point to a deleterious role of oxidatively modified
      molecules in early cell senescence of T21F, thereby linking replicative and
      stress-induced senescence in cultured cells to premature aging in DS. 

PMID- 25852820
TI  - Biomarkers of fatigue related to adjuvant chemotherapy for breast cancer:
      evaluation of plasma and lymphocyte expression.
AB  - BACKGROUND: Fatigue is common in cancer patients receiving adjuvant chemotherapy.
      To further understand the mechanism of fatigue and search for potential
      biomarkers, we conducted this prospective study. Methods We enrolled breast
      cancer (BC) patients before their first adjuvant Adriamycin-based chemotherapy
      cycle. Patients responded to the brief fatigue inventory (BFI) and Chalder
      fatigue questionnaires and had their blood drawn for both plasma evaluation and
      evaluation of the peripheral mononuclear cell fraction (PMNCF) mRNA expression of
      various biomarkers. We evaluated FSH, LH, estradiol, DHEA, DHEAS, IL6, IL2,
      ILIRA, IL1beta, CRP, Cortisol in the plasma and IL2, IL10, IL6, TGF-beta, KLRC1,
      TNF, BTP, SNCA, SOD1, BLNK, PTGS2 and INF gamma expression in the PMNCF. RESULTS:
      11 patients did not exhibit an increase in their BFI scores and served as
      controls, whereas 32 patients exhibited an increase in their BFI scores compared
      with the baseline scores. From the biomarkers we evaluated in the PMNCF, the only
      one significantly associated with fatigue was TGF-beta (p = 0.0343), while there
      was a trend towards significance with KLRC1 (p = 0.0627). We observed no evidence
      of significant associations of any plasma biomarkers with the development of
      fatigue. However when we analyzed patients with more severe fatigue, plasma IL1
      RA levels correlated directly with higher fatigue scores (p = 0.0136).
      CONCLUSIONS: We conclude that fatigue induced by chemotherapy in BC patients is
      associated with changes in IL1-ra plasma levels and in TGF-beta lymphocyte
      expression. Its mechanism may be different than that observed in long-term BC
      survivors or that induced by radiation therapy. TRIAL REGISTRATION: NCT02041364
      [ClinicalTrials.gov].

PMID- 25852819
TI  - Vaccination in children with allergy to non active vaccine components.
AB  - Childhood immunisation is one of the greatest public health successes of the last
      century. Vaccines contain an active component (the antigen) which induces the
      immune response. They may also contain additional components such as
      preservatives, additives, adjuvants and traces of other substances. This review
      provides information about risks of hypersensitivity reactions to components of
      vaccines. Furthermore, recommendations to avoid or reduce reactions to vaccine
      components have been detailed. 

PMID- 25852821
TI  - Clinical significance of monocyte heterogeneity.
AB  - Monocytes are primitive hematopoietic cells that primarily arise from the bone
      marrow, circulate in the peripheral blood and give rise to differentiated
      macrophages. Over the past two decades, considerable attention to monocyte
      diversity and macrophage polarization has provided contextual clues into the role
      of myelomonocytic derivatives in human disease. Until recently, human monocytes
      were subdivided based on expression of the surface marker CD16. "Classical"
      monocytes express surface markers denoted as CD14(++)CD16(-) and account for
      greater than 70% of total monocyte count, while "non-classical" monocytes express
      the CD16 antigen with low CD14 expression (CD14(+)CD16(++)). However, recognition
      of an intermediate population identified as CD14(++)CD16(+) supports the new
      paradigm that monocytes are a true heterogeneous population and careful
      identification of specific subpopulations is necessary for understanding monocyte
      function in human disease. Comparative studies of monocytes in mice have yielded
      more dichotomous results based on expression of the Ly6C antigen. In this review,
      we will discuss the use of monocyte subpopulations as biomarkers of human disease
      and summarize correlative studies in mice that may yield significant insight into
      the contribution of each subset to disease pathogenesis. 

PMID- 25852818
TI  - The significance of macrophage polarization subtypes for animal models of tissue
      fibrosis and human fibrotic diseases.
AB  - The systemic and organ-specific human fibrotic disorders collectively represent
      one of the most serious health problems world-wide causing a large proportion of
      the total world population mortality. The molecular pathways involved in their
      pathogenesis are complex and despite intensive investigations have not been fully
      elucidated. Whereas chronic inflammatory cell infiltration is universally present
      in fibrotic lesions, the central role of monocytes and macrophages as regulators
      of inflammation and fibrosis has only recently become apparent. However, the
      precise mechanisms involved in the contribution of monocytes/macrophages to the
      initiation, establishment, or progression of the fibrotic process remain largely
      unknown. Several monocyte and macrophage subpopulations have been identified,
      with certain phenotypes promoting inflammation whereas others display profibrotic
      effects. Given the unmet need for effective treatments for fibroproliferative
      diseases and the crucial regulatory role of monocyte/macrophage subpopulations in
      fibrogenesis, the development of therapeutic strategies that target specific
      monocyte/macrophage subpopulations has become increasingly attractive. We will
      provide here an overview of the current understanding of the role of
      monocyte/macrophage phenotype subpopulations in animal models of tissue fibrosis
      and in various systemic and organ-specific human fibrotic diseases. Furthermore,
      we will discuss recent approaches to the design of effective anti-fibrotic
      therapeutic interventions by targeting the phenotypic differences identified
      between the various monocyte and macrophage subpopulations. 

PMID- 25852824
TI  - A reply to the commentary on "Animal models of chronic tympanic membrane
      perforation: in response to plasminogen initiates and potentiates the healing of
      acute and chronic tympanic membrane perforations in mice" by Wang AY, Shen Y,
      Wang JT, Eikelboom RH and Dilley RJ; Clin Translat Med, 2014; 3:5.

PMID- 25852822
TI  - EMT and tumor metastasis.
AB  - EMT and MET comprise the processes by which cells transit between epithelial and
      mesenchymal states, and they play integral roles in both normal development and
      cancer metastasis. This article reviews these processes and the molecular
      pathways that contribute to them. First, we compare embryogenesis and development
      with cancer metastasis. We then discuss the signaling pathways and the
      differential expression and down-regulation of receptors in both tumor cells and
      stromal cells, which play a role in EMT and metastasis. We further delve into the
      clinical implications of EMT and MET in several types of tumors, and lastly, we
      discuss the role of epigenetic events that regulate EMT/MET processes. We
      hypothesize that reversible epigenetic events regulate both EMT and MET, and
      thus, also regulate the development of different types of metastatic cancers. 

PMID- 25852823
TI  - Understanding the MIND phenotype: macrophage/microglia inflammation in
      neurocognitive disorders related to human immunodeficiency virus infection.
AB  - Tissue macrophages play important roles in maintaining homeostasis in most organs
      of the body including the brain where microglia represent the resident phagocytic
      cells of this compartment. The possibility of one day harnessing macrophage
      plasticity to treat or ameliorate disorders including obesity, cancer, organ
      damage, intestinal disorders, neurodegeneration, and cardiovascular disease in
      which these cells play a role, is a very exciting prospect. Inflammatory
      signaling is required for regenerative repair, healing, and pathogen clearance
      functions. However, when the inflammatory response persists in a chronic fashion
      over an extended period of time, damage to neurons is followed by neuronal injury
      and dysfunction. Macrophages in the brain are heterogeneous arising from tissues
      during embryogenesis, and in the adult, from bone marrow derived monocytes that
      enter through the blood-brain-barrier. While much of our insight regarding
      macrophage functional subtypes has been garnered through elegant studies in mice,
      which are amenable to genetic manipulation, far less is known about such cells in
      human tissues, and particularly in the brain under normal, disease, or injurious
      conditions. In this regard, non-human primate models for human immunodeficiency
      virus have been extremely useful for understanding the contribution of bone
      marrow-derived monocytes in neurological disease and their interaction and impact
      on the activation state of resident microglia in the brain. This review will
      focus on what has been learned from the rhesus macaque models about the types of
      macrophages present in the brains of animals with encephalitis. In vitro studies,
      which have used human blood monocytes differentiated into macrophages to address
      the question of macrophage subsets in HIV infection will be highlighted. Recent
      insights on macrophage phenotype and persistent inflammation in the brain in HIV
      associated neurocognitive disorder from immunohistochemical studies on human
      autopsy tissue will be examined. 

PMID- 25852826
TI  - MELK-a conserved kinase: functions, signaling, cancer, and controversy.
AB  - Maternal embryonic leucine zipper kinase (MELK) is a highly conserved
      serine/threonine kinase initially found to be expressed in a wide range of early
      embryonic cellular stages, and as a result has been implicated in embryogenesis
      and cell cycle control. Recent evidence has identified a broader spectrum of
      tissue expression pattern for this kinase than previously appreciated. MELK is
      expressed in several human cancers and stem cell populations. Unique spatial and
      temporal patterns of expression within these tissues suggest that MELK plays a
      prominent role in cell cycle control, cell proliferation, apoptosis, cell
      migration, cell renewal, embryogenesis, oncogenesis, and cancer treatment
      resistance and recurrence. These findings have important implications for our
      understanding of development, disease, and cancer therapeutics. Furthermore
      understanding MELK signaling may elucidate an added dimension of stem cell
      control. 

PMID- 25852825
TI  - An engineered micropattern to reduce bacterial colonization, platelet adhesion
      and fibrin sheath formation for improved biocompatibility of central venous
      catheters.
AB  - BACKGROUND: Catheter-related bloodstream infections (CRBSIs) and catheter-related
      thrombosis (CRT) are common complications of central venous catheters (CVC),
      which are used to monitor patient health and deliver medications. CVCs are
      subject to protein adsorption and platelet adhesion as well as colonization by
      the natural skin flora (i.e. Staphylococcus aureus and Staphylococcus
      epidermidis). Antimicrobial and antithrombotic drugs can prevent infections and
      thrombosis-related complications, but have associated resistance and safety
      risks. Surface topographies have shown promise in limiting platelet and bacterial
      adhesion, so it was hypothesized that an engineered Sharklet micropattern,
      inspired by shark-skin, may provide a combined approach as it has wide reaching
      anti-fouling capabilities. To assess the feasibility for this micropattern to
      improve CVC-related healthcare outcomes, bacterial colonization and platelet
      interactions were analyzed in vitro on a material common for vascular access
      devices. METHODS: To evaluate bacterial inhibition after simulated vascular
      exposure, micropatterned thermoplastic polyurethane surfaces were preconditioned
      with blood proteins in vitro then subjected to a bacterial challenge for 1 and 18
      h. Platelet adhesion was assessed with fluorescent microscopy after incubation of
      the surfaces with platelet-rich plasma (PRP) supplemented with calcium. Platelet
      activation was further assessed by monitoring fibrin formation with fluorescent
      microscopy after exposure of the surfaces to platelet-rich plasma (PRP)
      supplemented with calcium in a flow-cell. Results are reported as percent
      reductions and significance is based on t-tests and ANOVA models of log
      reductions. All experiments were replicated at least three times. RESULTS: Blood
      and serum conditioned micropatterned surfaces reduced 18 h S. aureus and S.
      epidermidis colonization by 70% (p <= 0.05) and 71% (p < 0.01), respectively,
      when compared to preconditioned unpatterned controls. Additionally, platelet
      adhesion and fibrin sheath formation were reduced by 86% and 80% (p < 0.05),
      respectively, on the micropattern, when compared to controls. CONCLUSIONS: The
      Sharklet micropattern, in a CVC-relevant thermoplastic polyurethane,
      significantly reduced bacterial colonization and relevant platelet interactions
      after simulated vascular exposure. These results suggest that the incorporation
      of the Sharklet micropattern on the surface of a CVC may inhibit the initial
      events that lead to CRBSI and CRT.

PMID- 25852827
TI  - Neuropathic caner pain: is it linked to the recurrence of cancer?

PMID- 25852828
TI  - What is the Role of Epidural Injections in the Treatment of Lumbar Discogenic
      Pain: A Systematic Review of Comparative Analysis with Fusion.
AB  - BACKGROUND: Lumbar discogenic pain without pain mediated by a disc herniation,
      facet joints, or the sacroiliac joints, is common and often results in chronic,
      persistent pain and disability. After conservative treatment failure, injection
      therapy, such as an epidural injection, is frequently the next step considered in
      managing discogenic pain. The objective of this systematic review is to determine
      the efficacy of lumbar epidural injections in managing discogenic pain without
      radiculopathy, and compare this approach to lumbar fusion or disc arthroplasty
      surgery. METHODS: A systematic review of randomized trials published from 1966
      through October 2014 of all types of epidural injections and lumbar fusion or
      disc arthroplasty in managing lumbar discogenic pain was performed with
      methodological quality assessment and grading of evidence. The level of evidence
      was based on the grading of evidence criteria which, was conducted using 5 levels
      of evidence ranging from levels I to V. RESULTS: Based on a qualitative
      assessment of the evidence for both approaches, there is Level II evidence for
      epidural injections, either caudal or lumbar interlaminar. CONCLUSIONS: The
      available evidence suggests fluoroscopically directed epidural injections provide
      long-term improvement in back and lower extremity pain for patients with lumbar
      discogenic pain. There is also limited evidence showing the potential
      effectiveness of surgical interventions compared to nonsurgical treatments.

PMID- 25852829
TI  - Reducing Irrational Beliefs and Pain Severity in Patients Suffering from Non
      Cardiac Chest Pain (NCCP): A Comparison of Relaxation Training and Metaphor
      Therapy.
AB  - BACKGROUND: Patients suffering from non-cardiac chest pain (NCCP) can interpret
      their chest pain wrongly despite having received a correct diagnosis. The
      objective of this study was to compare the efficacy of the relaxation method with
      metaphor therapy for reducing irrational beliefs and pain severity in patients
      with NCCP. METHODS: Using a randomized controlled trial, 33 participants were
      randomly divided into a relaxation training group (n= 13), a metaphor therapy
      group (n = 10), and a control group (n = 10), and were studied for 4 weeks. The
      two tools used in this research were the Brief Pain Inventory (BPI) index for
      determining the degree of pain and the short version of the Jones Irrational
      Belief Test. Metaphor therapy and a relaxation technique based on Ost's treatment
      were used as the interventions. The collected data were analyzed with a
      multivariate analysis of covariance (MANCOVA), a Chi-square test, and the
      Bonferroni procedure of post-hoc analysis. RESULTS: The relaxation training
      method was significantly more effective than both metaphor therapy and the lack
      of treatment in reducing the patients' beliefs of hopelessness in the face of
      changes and emotional irresponsibility, as well as the pain severity. Metaphor
      therapy was not effective on any of these factors. In fact, the results did not
      support the effectiveness of metaphor therapy. CONCLUSIONS: Regarding the
      effectiveness of the relaxation method as compared with metaphor therapy and the
      lack of treatment in the control group, this study suggests that relaxation
      should be paid greater attention as a method for improving the status of
      patients. In addition, more studies are needed to determine the effectiveness of
      metaphor therapy in this area.

PMID- 25852830
TI  - Anti-allodynic Efficacy of NMDA Antagonist Peptide and Noradrenaline Alone and in
      Combination in Rodent Neuropathic Pain Model.
AB  - BACKGROUND: The present experiment was conducted to identify the cooperative
      effect of serine histogranin (SHG) and noradrenaline in alleviating peripheral
      neuropathic pain. METHODS: Chronic constriction injury of the right sciatic nerve
      was used to induce chronic neuropathic pain. For drug delivery, a PE10 tube was
      inserted into the subarachnoid space. Acetone drops and a 44C water bath were
      used to evaluate the cold and heat allodynia, respectively. Placing and grasping
      reflexes were used to assess the locomotor system. RESULTS: SHG at 0.5 and 1 ug
      significantly (P < 0.05) decreased the thermal allodynia. The cold allodynia was
      also significantly reduced by intrathecal injections of 0.5 (P < 0.05) and 1 ug
      (P < 0.001) of SHG. 1 ug of noradrenaline, but not 0.5 ug, significantly
      alleviated the cold (P < 0.01) and thermal (P < 0.05) allodynia. The ameliorating
      effect of noradrenaline or SHG disappeared when the two compounds were
      administrated in equal concentrations. A significant difference (P < 0.01 in the
      acetone and P < 0.05 in the heat) was observed in the groups under equal doses of
      the two compounds, with a lower effectiveness of the combination therapy.
      CONCLUSIONS: Our findings suggest that the simultaneous administrations of
      noradrenaline and SHG do not result in synergistic analgesia, and combination
      therapy may not be a good approach to the treatment of chronic neuropathic pain
      syndrome.

PMID- 25852831
TI  - Detection Rate of Intravascular Injections during Cervical Medial Branch Blocks:
      A Comparison of Digital Subtraction Angiography and Static Images from
      Conventional Fluoroscopy.
AB  - BACKGROUND: The most definitive diagnosis of neck pain caused by facet joints can
      be obtained through cervical medial branch blocks (CMBBs). However, intravascular
      injections need to be carefully monitored, as they can increase the risk of false
      negative blocks when diagnosing cervical facet joint syndrome. In addition,
      intravascular injections can cause neurologic deficits such as spinal infarction
      or cerebral infarction. Digital subtraction angiography (DSA) is a radiological
      technique that can be used to clearly visualize the blood vessels from
      surrounding bones or dense soft tissues. The purpose of this study was to compare
      the rate of detection of intravascular injections during CMBBs using DSA and
      static images obtained through conventional fluoroscopy. METHODS: Seventy-two
      patients were included, and a total of 178 CMBBs were performed. The respective
      incidences of intravascular injections during CMBBs using DSA and static images
      from conventional fluoroscopy were measured. RESULTS: A total of 178 CMBBs were
      performed on 72 patients. All cases of intravascular injections evidenced by the
      static images were detected by the DSAs. The detection rate of intravascular
      injections was higher from DSA images than from static images (10.7% vs. 1.7%, P
      < 0.001). CONCLUSIONS: According to these findings, the use of DSA can improve
      the detection rate of intravascular injections during CMBBs. The use of DSA may
      therefore lead to an increase in the diagnostic and therapeutic value of CMBBs.
      In addition, it can decrease the incidence of potential side effects during
      CMBBs.

PMID- 25852832
TI  - Alternative Method of Retrocrural Approach during Celiac Plexus Block Using a
      Bent Tip Needle.
AB  - BACKGROUND: This study sought to determine safe ranges of oblique angle, skin
      entry point and needle length by reviewing computed tomography (CT) scans and to
      evaluate the usefulness of a bent tip needle during celiac plexus block (CPB).
      METHODS: CT scans of 60 CPB patients were reviewed. Image of the uppermost margin
      of L2 vertebral body was used to measure the minimal and maximal oblique angles
      and the distances from the midline to skin puncture point. The imaginary needle
      trajectory distance was calculated by three-dimensional measurement. When the
      procedure was performed by using a 10 degrees  bent tip needle under a 20 degrees
      oblique X-ray fluoroscopic view, the distance (GF/G'F) from the midline to the
      actual puncture site was measured. RESULTS: The imaginary safe oblique angle
      range was 26.4-34.2 degrees  and 27.7-36.0 degrees  on the right and left,
      respectively. The distance from the midline to skin puncture point was 6.1-7.6 cm
      on the right and 6.3-7.6 cm on the left. The needle trajectory distance at
      minimal angle was 9.6-11.6 cm on the right and 9.5-11.5 cm on the left. The
      distance of GF/G'F was 5.1-6.5 cm and 5.0-6.4 cm on the right and left,
      respectively. All imaginary parameters were correlated with BMI except for
      GF/G'F. All complications were mild and transient. CONCLUSIONS: We identified
      safe values of angles and distances using a straight needle. Furthermore, using a
      bent tip needle under a 20 degrees  oblique fluoroscopic view, we could safely
      perform CPB with smaller parameter values.

PMID- 25852833
TI  - Persistent Post-radiotherapy Pain and Locoregional Recurrence in Head and Neck
      Cancer-Is There a Hidden Link?
AB  - BACKGROUND: To explore the relationship between persistent post-radiotherapy pain
      and locoregional recurrence in head and neck cancer patients. METHODS: Five year
      retrospective data was reviewed of 86 patients of head and neck cancer treated
      with radiotherapy who continued to have pain at 6 weeks after completion of
      treatment. At follow-up after 3 months, these patients were stratified into:
      Group A (n = 39) constituted of patients whose pain subsided and Group B (n = 47)
      were patients who continued to have persistent pain. RESULTS: At median follow-up
      time of 25 months (range: 8-47), one patient (2.6%) and 18 (38.3%) patients in
      group A and group B had locoregional recurrence respectively (P < 0.0001).
      Furthermore, group B patients had higher mean pain score levels as compared to
      group A (P = 0.03). Patients in whom pain subsided within 3 months had
      statistically much greater disease-free survival in comparison to those with
      persistent pain (P < 0.0001). CONCLUSIONS: Pain in head and neck cancer is an
      important symptom and should be considered a poor prognostic factor. In the
      current study, the majority of the patients with persistent pain had recurrent
      disease as compared to those in whom pain subsided within 3 months of post
      treatment. It is suggested that patients with persistent pain need more intense
      follow-up and should be investigated thoroughly to detect recurrence at an early
      stage to provide a better quality of life.

PMID- 25852834
TI  - A Comparison of Two Techniques for Ultrasound-guided Caudal Injection: The
      Influence of the Depth of the Inserted Needle on Caudal Block.
AB  - BACKGROUND: Caudal epidural injections have been commonly performed in patients
      with low back pain and radiculopathy. Although caudal injection has generally
      been accepted as a safe procedure, serious complications such as inadvertent
      intravascular injection and dural puncture can occur. The present prospective
      study was designed to investigate the influence of the depth of the inserted
      needle on the success rate of caudal epidural blocks. METHODS: A total of 49
      adults scheduled to receive caudal epidural injections were randomly divided into
      2 groups: Group 1 to receive the caudal injection through a conventional method,
      i.e., caudal injection after advancement of the needle 1 cm into the sacral canal
      (n = 25), and Group 2 to receive the injection through a new method, i.e.,
      injection right after penetrating the sacrococcygeal ligament (n = 24).
      Ultrasound was used to identify the sacral hiatus and to achieve accurate needle
      placement according to the allocated groups. Contrast dyed fluoroscopy was
      obtained to evaluate the epidural spread of injected materials and to monitor the
      possible complications. RESULTS: The success rates of the caudal injections were
      68.0% in Group 1 and 95.8% in Group 2 (P = 0.023). The incidences of
      intravascular injections were 24.0% in Group 1 and 0% in Group 2 (P = 0.022). No
      intrathecal injection was found in either of the two groups. CONCLUSIONS: The new
      caudal epidural injection technique tested in this study is a reliable
      alternative, with a higher success rate and lower risk of accidental
      intravascular injection than the conventional technique.

PMID- 25852835
TI  - Evaluation of pain and its effect on quality of life and functioning in men with
      spinal cord injury.
AB  - BACKGROUND: Pain is one of the most important consequences of spinal cord injury
      (SCI). It may affect several aspects of life, especially the quality of life
      (QoL). Hence, this study was conducted to establish an understanding of pain and
      its correlates and effects on patients with SCI in our community. METHODS: In a
      cross-sectional study, 58 male veterans suffering from SCI were admitted to our
      center for a regular follow-up. Demographic and SCI-related descriptive
      information were gathered using a self-reported questionnaire. To evaluate the
      patients' pain quality and the effect of pain on daily life, a questionnaire in 3
      parts of lumbar, cervical and shoulder pain was administered. EuroQoL
      questionnaire and General Health Questionnaire (GHQ) 12 were also used to assess
      the patients' QoL. RESULTS: The mean age of the participants was 45.91 +/- 6.69
      with mean injury time of 25.54 +/- 5.91. forty-four patients (75.9%) reported
      pain, including lumbar pain (63%), cervical pain (39%) and shoulder pain (51%).
      The presence of pain was associated with lower QoL. Patients with lumbar pain
      reported a significant amount of pain affecting their daily life and this effect
      was higher in patients with lower GHQ score or anxiety/depressive disorder.
      CONCLUSIONS: Musculoskeletal pain, is a common complaint in veterans with SCI and
      is inversely associated with functioning and general health status. Lumbar and
      shoulder pain affects patient's daily living more than cervical pain.

PMID- 25852836
TI  - Risk factors associated with clinical insomnia in chronic low back pain: a
      retrospective analysis in a university hospital in Korea.
AB  - BACKGROUND: Insomnia is becoming increasingly recognized as a clinically
      important symptom in patients with chronic low back pain (CLBP). In this
      retrospective study, we have determined risk factors associated with clinical
      insomnia in CLBP patients in a university hospital in Korea. METHODS: Data from
      four-hundred and eighty one CLBP patients was analyzed in this study. The
      Insomnia Severity Index (ISI) was used to determine the presence of clinical
      insomnia (ISI score >= 15). Patients' demographics and pain-related factors were
      evaluated by logistic regression analysis to identify risk factors of clinical
      insomnia in CLBP. RESULTS: It was found that 43% of patients reported mild to
      severe insomnia after the development of back pain. In addition, 20% of patients
      met the criteria for clinically significant insomnia (ISI score >= 15). In a
      stepwise multivariate analysis, high pain intensity, the presence of comorbid
      musculoskeletal pain and neuropathic pain components, and high level of
      depression were strongly associated with clinical insomnia in CLBP. Among these
      factors, the presence of comorbid musculoskeletal pain other than back pain was
      the strongest determinant, with the highest odds ratio of 8.074 (95% CI 4.250 to
      15.339) for predicting clinical insomnia. CONCLUSIONS: Insomnia should be
      addressed as an integral part of pain management in CLBP patients with these risk
      factors, especially in patients suffering from CLBP with comorbid musculoskeletal
      pain.

PMID- 25852837
TI  - Acute motor weakness of opposite lower extremity after percutaneous epidural
      neuroplasty.
AB  - Recently, percutaneous epidural neuroplasty has become widely used to treat
      radicular pain caused by spinal stenosis or a herniated intervertebral disc. A 19
      year-old female patient suffering from left radicular pain caused by an L4-L5
      intervertebral disc herniation underwent percutaneous epidural neuroplasty of the
      left L5 nerve root using a Racz catheter. After the procedure, the patient
      complained of acute motor weakness in the right lower leg, on the opposite site
      to where the neuroplasty was conducted. Emergency surgery was performed, and
      swelling of the right L5 nerve root was discovered. The patient recovered her
      motor and sensory functions immediately after the surgery. Theoretically, the
      injection of a large volume of fluid in a patient with severe spinal stenosis
      during epidural neuroplasty can increase the pressure on the opposite side of the
      epidural space, which may cause injury of the opposite nerve by barotrauma from a
      closed compartment. Practitioners should be aware of this potential complication.

PMID- 25852838
TI  - Paraplegia following intercostal nerve neurolysis with alcohol and thoracic
      epidural injection in lung cancer patient.
AB  - The goal of cancer treatment is generally pain reduction and function recovery.
      However, drug therapy does not treat pain adequately in approximately 43% of
      patients, and the latter may have to undergo a nerve block or neurolysis. In the
      case reported here, a 42-year-old female patient with lung cancer
      (adenocarcinoma) developed paraplegia after receiving T8-10 and 11(th)
      intercostal nerve neurolysis and T9-10 interlaminar epidural steroid injections.
      An MRI results revealed extensive swelling of the spinal cord between the T4
      spinal cord and conus medullaris, and T5, 7-11, and L1 bone metastasis. Although
      steroid therapy was administered, the paraplegia did not improve. 

PMID- 25852839
TI  - Delayed allergic reaction to secondary administrated epidural hyaluronidase.
AB  - We are reporting a rare case of a delayed hypersensitivity reaction caused by
      hyaluronidase allergy following a lumbar transforaminal epidural block. Using an
      intradermal skin test, we have provided evidence that the systemic allergic
      reaction resulted from hypersensitivity to hyaluronidase. To our knowledge, this
      is a rare case of a delayed hypersensitivity reaction to epidural hyaluronidase,
      comprised of an initial exposure to hyaluronidase with no subsequent allergic
      response in prior block followed by a subsequent delayed reaction to
      hyaluronidase during a second epidural block. 

PMID- 25852840
TI  - Combined use of intrathecal opioids and dexmedetomidine in the management of
      neuropathic pain.

PMID- 25852841
TI  - An update on the management of diabetic neuropathic pain: a few comments.

PMID- 25852842
TI  - Bedside ultrasound training using web-based e-learning and simulation early in
      the curriculum of residents.
AB  - BACKGROUND: Focused bedside ultrasound is rapidly becoming a standard of care to
      decrease the risks of complications related to invasive procedures. The purpose
      of this study was to assess whether adding to the curriculum of junior residents
      an educational intervention combining web-based e-learning and hands-on training
      would improve the residents' proficiency in different clinical applications of
      bedside ultrasound as compared to using the traditional apprenticeship teaching
      method alone. METHODS: Junior residents (n = 39) were provided with two
      educational interventions (vascular and pleural ultrasound). Each intervention
      consisted of a combination of web-based e-learning and bedside hands-on training.
      Senior residents (n = 15) were the traditionally trained group and were not
      provided with the educational interventions. RESULTS: After the educational
      intervention, performance of the junior residents on the practical tests was
      superior to that of the senior residents. This was true for the vascular
      assessment (94% +/- 5% vs. 68% +/- 15%, unpaired student t test: p < 0.0001, mean
      difference: 26 (95% CI: 20 to 31)) and even more significant for the pleural
      assessment (92% +/- 9% vs. 57% +/- 25%, unpaired student t test: p < 0.0001, mean
      difference: 35 (95% CI: 23 to 44)). The junior residents also had a significantly
      higher success rate in performing ultrasound-guided needle insertion compared to
      the senior residents for both the transverse (95% vs. 60%, Fisher's exact test p
      = 0.0048) and longitudinal views (100% vs. 73%, Fisher's exact test p = 0.0055).
      CONCLUSIONS: Our study demonstrated that a structured curriculum combining web
      based education, hands-on training, and simulation integrated early in the
      training of the junior residents can lead to better proficiency in performing
      ultrasound-guided techniques compared to the traditional apprenticeship model.

PMID- 25852843
TI  - Case report: an unrecognized etiology of transient gallbladder pain in heart
      failure diagnosed with internist-performed point-of-care ultrasound.
AB  - The excellent sensitivity and specificity of right upper quadrant (RUQ)
      ultrasound for gallbladder pathology in patients with abdominal pain is heavily
      relied upon in routine diagnostic evaluation. The hour-to-hour timing of this
      test in a patient with fluctuating symptoms is not widely recognized as having a
      significant impact on its sensitivity. However, we present a case report
      describing the essential role of symptom-timed point-of-care ultrasound in making
      an elusive diagnosis of transient cholecystalgia in a patient with RUQ pain and
      congestive heart failure (CHF). This case also demonstrates an important etiology
      of RUQ pain in patients with CHF beyond that of congestive hepatopathy. A review
      of the related entities of acalculous cholecystitis, congestive hepatopathy, and
      diffuse gallbladder wall thickening is provided. 

PMID- 25852844
TI  - A rare cause of acquired immune deficiency syndrome related pancytopenia.
AB  - A 21-year-old male with acquired immune deficiency syndrome, not on highly active
      antiretroviral treatment (HAART) was admitted after complaining of headache and
      intermittent diarrhea, found to have Cryptococcal meningitis. During the course
      of his hospitalization, patient developed pancytopenia. Anemia panel, serologies
      including Epstein barr virus, cytomegalovirus, and parvovirus were negative.
      Patient then developed high grade fever with elevated liver enzymes. Blood
      cultures, urine cultures, stool cultures, and repeat cerebrospinal fluid cultures
      remained negative. Patient subsequently developed skin lesions which on biopsy
      showed Kaposi's sarcoma, and upon endoscopy, noted to have gastrointestinal
      Kaposi's sarcoma involvement. Human herpes virus 8 was positive. Bone marrow
      biopsy revealed hemophagocytic lymphohistiocytosis. Despite having a concern for
      patient developing immune reconstitution syndrome which may worsen his
      meningitis, HAART was initiated and patient's symptoms improved including
      resolution of fevers and hematological as well as liver abnormalities. Kaposi's
      sarcoma improved as well. 

PMID- 25852845
TI  - Interferon alpha Therapy in Patients with Chronic Hepatitis C Infection: Quality
      of Life and Depression.
AB  - Health-related quality of life was examined in 49 patients with hepatitis C virus
      with no psychiatric history who received interferon (IFN)-alpha treatment.
      Quality of life was assessed at baseline, at 3-time points during IFN-alpha
      therapy and at 1-6 month follow-up, using SF-36. Hepatitis C virus patients
      showed poorer physical functioning and better social and mental functioning than
      a normal population. Significant decreases from baseline SF-36 scores were
      observed at an early phase of treatment. Six patients developed major depression
      during IFN-alpha treatment. At baseline, they had reported more bodily pain than
      patients who did not develop depression during treatment. Planned contrasts
      revealed that worsening in some dimensions of quality of life at 2 months was
      greater in depressed than in non-depressed patients. Results suggest that
      depressive symptoms should be accurately monitored during IFN-alpha therapy even
      in patients with no psychiatric history, especially if they present with bodily
      pain. 

PMID- 25852846
TI  - Acute iatrogenic polycythemia induced by massive red blood cell transfusion
      during subtotal abdominal colectomy.
AB  - A 46 year old man was transfused ten units of packed red blood cells during
      subtotal colectomy after intraoperative point-of-care testing values demonstrated
      hemoglobin values less than seven grams per deciliter (g/dL). A postoperative
      hemoglobin analyzed in a standard hematologic laboratory revealed a hemoglobin
      value of 27.8 g/dL. He underwent emergent red blood cell depletion therapy which
      decreased his hemoglobin to 7.5 g/dL. The physiologic consequences of iatrogenic
      polycythemia caused by massive transfusion during major abdominal surgery must
      take into account the fluid shifts that interplay between the osmotic load,
      viscosity of blood, and postoperative third spacing of fluid. Treatment of acute
      iatrogenic polycythemia can be effectively accomplished by red blood cell
      depletion therapy. However, fluid shifts caused by massive transfusion followed
      by rapid red cell depletion produce a unique physiologic state that is without a
      well-described algorithm for management. 

PMID- 25852847
TI  - Emergency management of major bleeding in a case of maxillofacial trauma and
      anticoagulation: utility of prothrombin complex concentrates in the shock room.
AB  - Life-threatening bleeding in anticoagulation with Warfarin is an emergency
      challenging issue. Several approaches are available to treat bleeding in either
      over-anticoagulation or proper-anticoagulation, including vitamin K, fresh frozen
      plasma and prothrombin complex concentrates (PCC) administration. In coexisting
      trauma-induced bleeding and anticoagulation, reversal of anticoagulation must be
      a rapid and highly effective procedure. Furthermore the appropriate treatment
      must be directly available in each shock rooms to guarantee the rapid management
      of the emergency. PCC require a simple storage, rapid accessibility, fast
      administration procedures and high effectiveness. Here we report the utility of
      PCC in management of a craniofacial trauma in proper-anticoagulation. 

PMID- 25852848
TI  - Feasibility of romiplostim discontinuation in adult thrombopoietin-receptor
      agonist responsive patients with primary immune thrombocytopenia: an
      observational retrospective report in real life clinical practice.
AB  - Thrombopoietin mimetics are new treatment options for patients with immune throm
      bocytopenia (ITP). Because of their mechanism of action, long-term administration
      was envisioned in order to maintain effective thrombopoiesis. We report on 30
      romiplostim treated patients: 13/27 responders (48%) achieved stable platelet
      counts on a mean romiplostim dose of 2.43 ug/kg and were able to stop romiplostim
      after a mean of 44.3 weeks (range 12-122) on therapy with sustained response
      maintained at a mean of 26 months (range 12-52). No bleeding events occurred
      during the observational period. No specific patient's features nor pattern of
      early response seemed to predict for sustained response. However, patients
      achieving safe platelet counts at lower dosages are probably worth a try of
      therapy tapering and discontinuation. Our observations support feasibility of
      romiplostim safe suspension in a relevant proportion of ITP patients. 

PMID- 25852849
TI  - Complex karyotype with novel translocation in pure erythroid leukemia patient.
AB  - Pure erythroid leukemia (PEL) is rare hematopoietic neoplasm characterized by
      uncontrolled proliferation of immature erythroid precursors - mainly abnormal
      proery-throblasts - comprising at least 80% of bone marrow cells. In this paper,
      I present a case of 48 years old patient, who presented with pancytopenia and
      circulating erythroblast in peripheral blood after long history of alcohol abuse.
      Bone marrow examination revealed hypercellular marrow which is markedly
      infiltrated with immature erythroid precursors. An expanded panel of
      immunophenotyping markers has confirmed the diagnosis of PEL. Cytogenetics
      analysis detected a complex karyotype with multiple chromosomal abnormalities and
      a novel translocation, t(8;9) (p11.2;q12), which has not been reported in acute
      myeloid leukemia (AML) in the past. The patient was treated with standard AML
      chemotherapy but he did not show an optimal response and passed away. An updated
      and short review about various aspects of PEL has been made with special focus on
      immunophenotyping and genetic studies. 

PMID- 25852850
TI  - Central neurotoxicity of immunomodulatory drugs in multiple myeloma.
AB  - Immunomodulatory drugs (IMiDs) currently used in the treatment of multiple
      myeloma, are thalidomide, lenalidomide and pomalidomide. One of the most common
      side effects of thalidomide is neurotoxicity, predominantly in the form of
      peripheral neuropathy. We report 6 cases of significant central neurotoxicity
      associated with IMiD therapy. Treatment with thalidomide (1 patient),
      lenalidomide (4 patients), and pomalidomide (1 patient) was associated with
      various clinical manifestations of central neurotoxicity, including reversible
      coma, amnesia, expressive aphasia, and dysarthria. Central neurotoxicity should
      be recognized as an important side effect of IMiD therapy. 

PMID- 25852851
TI  - Pulmonary extramedullary hematopoiesis involving the pulmonary artery.
AB  - Extramedullary hematopoiesis (EMH) occurs as a complication of hematologic
      disorders such as myelofibrosis, sickle cell anemia and thalassemia. The
      extramedullary tissue usually involves liver, spleen and lymph nodes, less
      frequently the chest. We present a recent case of a man with myeloproliferative
      neoplasm who developed pulmonary hemorrhage secondary to EMH in the lung and
      pulmonary artery. Radiation therapy was considered the best approach, but it
      didn't work and the patient died a week after radiation therapy was completed. We
      also review herein the present literature. 

PMID- 25852852
TI  - CLO: The cell line ontology.
AB  - BACKGROUND: Cell lines have been widely used in biomedical research. The
      community-based Cell Line Ontology (CLO) is a member of the OBO Foundry library
      that covers the domain of cell lines. Since its publication two years ago,
      significant updates have been made, including new groups joining the CLO
      consortium, new cell line cells, upper level alignment with the Cell Ontology
      (CL) and the Ontology for Biomedical Investigation, and logical extensions.
      CONSTRUCTION AND CONTENT: Collaboration among the CLO, CL, and OBI has
      established consensus definitions of cell line-specific terms such as 'cell
      line', 'cell line cell', 'cell line culturing', and 'mortal' vs. 'immortal cell
      line cell'. A cell line is a genetically stable cultured cell population that
      contains individual cell line cells. The hierarchical structure of the CLO is
      built based on the hierarchy of the in vivo cell types defined in CL and tissue
      types (from which cell line cells are derived) defined in the UBERON cross
      species anatomy ontology. The new hierarchical structure makes it easier to
      browse, query, and perform automated classification. We have recently added
      classes representing more than 2,000 cell line cells from the RIKEN BRC Cell Bank
      to CLO. Overall, the CLO now contains ~38,000 classes of specific cell line cells
      derived from over 200 in vivo cell types from various organisms. UTILITY AND
      DISCUSSION: The CLO has been applied to different biomedical research studies.
      Example case studies include annotation and analysis of EBI ArrayExpress data,
      bioassays, and host-vaccine/pathogen interaction. CLO's utility goes beyond a
      catalogue of cell line types. The alignment of the CLO with related ontologies
      combined with the use of ontological reasoners will support sophisticated
      inferencing to advance translational informatics development.

PMID- 25852854
TI  - Rodent models of osteoporosis.
AB  - The aim of this protocol is to provide a detailed description of male and female
      rodent models of osteoporosis. In addition to indications on the methods of
      performing the surgical procedures, the choice of reliable and safe anaesthetics
      is also described. Post-operative care, including analgesia administration for
      pain management, is also discussed. Ovariectomy in rodents is a procedure where
      ovaries are surgically excised. Hormonal changes resulting from ovary removal
      lead to an oestrogen-deprived state, which enhances bone remodelling, causes bone
      loss and increases bone fracture risk. Therefore, ovariectomy has been considered
      as the most common preclinical model for understanding the pathophysiology of
      menopause-associated events and for developing new treatment strategies for
      tackling post-menopausal osteoporosis. This protocol also provides a detailed
      description of orchidectomy, a model for androgen-deficient osteoporosis in
      rodents. Endocrine changes following testes removal lead to hypogonadism, which
      results in accelerated bone loss, increasing osteoporosis risk. Orchidectomised
      rodent models have been proposed to mimic male osteoporosis and therefore remain
      a valuable tool for understanding androgen deficiency in aged men. Although it
      would have been particularly difficult to assemble an internationally acceptable
      description of surgical procedures, here we have attempted to provide a
      comprehensive guide for best practice in performing ovariectomy and orchidectomy
      in laboratory rodents. Research scientists are reminded that they should follow
      their own institution's interpretation of such guidelines. Ultimately, however,
      all animal procedures must be overseen by the local Animal Welfare and Ethical
      Review Body and conducted under licences approved by a regulatory ethics
      committee. 

PMID- 25852853
TI  - Pollen Allergies in Humans and their Dogs, Cats and Horses: Differences and
      Similarities.
AB  - Both humans and their most important domestic animals harbor IgE and a similar
      IgE receptor repertoire and expression pattern. The same cell types are also
      involved in the triggering or regulation of allergies, such as mast cells,
      eosinophils or T-regulatory cells. Translational clinical studies in domestic
      animals could therefore help cure animal allergies and at the same time gather
      knowledge relevant to human patients. Dogs, cats and horses may spontaneously and
      to different extents develop immediate type symptoms to pollen allergens. The
      skin, nasal and bronchial reactions, as well as chronic skin lesions due to
      pollen are in principle comparable to human patients. Pollen of various species
      most often causes allergic rhinitis in human patients, whereas in dogs it elicits
      predominantly eczematous lesions (canine atopic dermatitis), in horses recurrent
      airway obstruction or hives as well as pruritic dermatitis, and in cats bronchial
      asthma and so-called cutaneous reactive patterns (eosinophilic granuloma complex,
      head and neck pruritus, symmetric self-induced alopecia). In human allergy
      specific IgE detection, skin tests or other allergen provocation tests should be
      completed. In contrast, in animals IgE and dermal tests are regarded as equally
      important and may even replace each other. However, for practical and economic
      reasons intradermal tests are most commonly performed in a specialized practice.
      As in humans, in dogs, cats and horses allergen immunotherapy leads to
      significant improvement of the clinical symptoms. The collected evidence suggests
      that canines, felines and equines, with their spontaneous allergies, are
      attractive model patients for translational studies. 

PMID- 25852855
TI  - Magnesium: a renewed player of vascular ageing in diabetic CKD patients?

PMID- 25852856
TI  - Amyloid nephropathy.
AB  - Amyloidosis is an uncommon disease that is characterized by abnormal
      extracellular deposition of misfolded protein fibrils leading to organ
      dysfunction. The deposited proteins display common chemical and histologic
      properties but can vary dramatically in their origin. Kidney disease is a common
      manifestation in patients with systemic amyloidosis with a number of
      amyloidogenic proteins discovered in kidney biopsy specimens. The emergence of
      mass spectrometry-based proteomics has added to the diagnostic accuracy and
      overall understanding of amyloidosis. This in-depth review discusses the general
      histopathologic features of renal amyloidosis and includes an in-depth discussion
      of specific forms of amyloid affecting the kidney. 

PMID- 25852857
TI  - Clinicopathological assessment of the nephron number.
AB  - Recent studies have demonstrated much larger variability in the total number of
      nephrons in normal populations than previously suspected. In addition, it has
      been suggested that individuals with a low nephron number may have an increased
      lifetime risk of hypertension or renal insufficiency, emphasizing the importance
      of evaluating the nephron number in each individual. In view of the fact that all
      previous reports of the nephron number were based on analyses of autopsy kidneys,
      the identification of surrogate markers detectable in living subjects is needed
      in order to enhance understanding of the clinical significance of this parameter.
      In this review, we summarize the clinicopathological factors and findings
      indicating a reduction in the nephron number, focusing particularly on those
      found at the time of a preserved renal function. 

PMID- 25852858
TI  - Oedema, solid organ transplantation and mammalian target of rapamycin
      inhibitor/proliferation signal inhibitors (mTOR-I/PSIs).
AB  - Mammalian target of rapamycin inhibitor (mTOR-I)/proliferation signal inhibitors
      (PSI) including sirolimus and everolimus represent a new class of drugs
      increasingly used in solid-organ transplantation as alternatives to calcineurin
      inhibitors for patients with renal dysfunction, transplant coronary arterial
      vasculopathy or malignancy. The most frequently occurring mTOR-I/PSI-related
      adverse events are similar to those associated with other immunosuppressive
      therapies, but some side effects are more characteristic of proliferation signal
      inhibitors (e.g. lymphocele, arthralgia, oedema and hyperlipidaemia). The present
      paper review incidence, clinical presentation and mechanism of oedema within the
      clinical experience of mTOR-I/PSI in solid organ transplantation. 

PMID- 25852859
TI  - HIV medication-based urolithiasis.
AB  - Drug-induced renal calculi represent 1-2% of all renal calculi. In the last
      decade, drugs used for the treatment of HIV-infected patients have become the
      most frequent cause of drug-containing urinary calculi. Among these agents,
      protease inhibitors (PIs) are well known to induce kidney stones, especially
      indinavir and atazanavir, and more recently darunavir. Urolithiasis attributable
      to other PIs has also been reported in clinical cases such as those during non-PI
      use. Antiretroviral drug-induced calculi deserve consideration because most of
      them are potentially preventable. This article summarizes the diagnosis,
      epidemiology, prevention and management of antiretroviral drug-induced
      urolithiasis. 

PMID- 25852860
TI  - Severe hyperkalaemia: demographics and outcome.
AB  - BACKGROUND: Few studies have evaluated the prevalence of severe hyperkalaemia in
      unselected patient populations. We identified all episodes of severe
      hyperkalaemia occurring in 1 year, and described patient demographics, clinical
      response and outcome. We also assessed junior doctor knowledge of its causes and
      significance. MATERIALS AND METHODS: A retrospective interrogation of the
      database of the regional biochemical laboratory identified all episodes of severe
      hyperkalaemia (K>= 6.5 mmol/L) occurring in 2011. The understanding of trainee
      doctors of the importance, causes and treatment of severe hyperkalaemia was
      assessed by structured questionnaire. RESULTS: Severe hyperkalaemia was recorded
      in 433 samples (365 patients) giving a prevalence of 0.11%. Thirty-six per cent
      of episodes occurred in patients under the care of a nephrologist, who were
      significantly younger than those not under the care of a nephrologist. In the
      nephrology cohort, 86% occurred in patients with chronic kidney disease (CKD),
      the majority of which had CKD Stage 5. In the non-nephrology cohort, only 65%
      occurred in the context of CKD, which was equally distributed between Stages 3
      and 5 CKD. In both patient groups, roughly 50% of episodes occurred in
      association with acute kidney injury (AKI). Acute mortality (death within 48 h of
      documented severe hyperkalaemia) was higher in the non-nephrology compared with
      the nephrology cohort. Time to repeat serum potassium was influenced by the
      clinical setting with shorter time to repeat for acute care compared with ward
      settings. Assessment of trainee doctor's knowledge suggested significant
      deficiencies in relation to severe hyperkalaemia. CONCLUSIONS: The prevalence of
      severe hyperkalaemia was low and occurred predominantly in the context of CKD
      and/or AKI. The majority of episodes occurred in patients not under the care of a
      nephrologist. Variability in time to repeat serum potassium levels suggested
      deficiencies in care, and assessment of trainee doctor's knowledge suggests the
      need for further educational initiatives to highlight its importance.

PMID- 25852861
TI  - Renal manifestations of tuberous sclerosis among children: an Indian experience
      and review of the literature.
AB  - OBJECTIVE: The objective of this study was to describe the renal manifestations
      in children 0-18 years of age diagnosed with tuberous sclerosis complex (TSC) at
      a tertiary hospital in South India. METHODS: Data of children with TSC, who
      presented to Christian Medical College Vellore Hospital from January 2008 to
      January 2013, were analysed by a retrospective chart review. The cases were
      identified from outpatient records and underwent ultrasonography, urine analysis
      and examination of serum creatinine to recognize renal involvement. RESULTS:
      Twenty-five children with TSC were identified. Two children did not have imaging
      studies available and were excluded from the analysis. The age of the included
      children ranged from 5 days to 15 years with a median age of 8 years. Seventy
      four per cent (17/23) were males. Ten of the 23 children had evidence of renal
      involvement (43.5%). Of the 10 children with renal involvement, 6 had
      angiomyolipoma (60%), 5 had renal cysts (50%) and 1 had suspected renal cell
      carcinoma. In two children both angiomyolipoma (AML) and cysts were noted. One
      child was found to have proteinuria. The rest of the children had no evidence of
      proteinuria and had normal creatinine clearance. CONCLUSION: We conclude that all
      children with TSC should be screened for renal involvement and regular follow-up
      should be arranged.

PMID- 25852862
TI  - Polycystic kidney size and outcomes on peritoneal dialysis: comparison with
      haemodialysis.
AB  - BACKGROUND: For many nephrologists, patients with polycystic kidney disease (PKD)
      have an increased risk of complications and technique failure on peritoneal
      dialysis (PD) due to enlarged kidneys. The literature showed that PD can be as
      good a therapeutic option as haemodialysis (HD) for patients with PKD. However,
      no study has focused on the impact of polycystic kidney size on outcomes for
      patients on PD. METHODS: This is a retrospective monocentric study. Fifty-eight
      patients with PKD started dialysis between January 2000 and December 2010: 24 on
      PD and 34 on HD. Kidney size assessed by abdominal computed tomography scans was
      available for 45 patients (19 on PD and 26 on HD). PD technique survival,
      specific PKD complications and mechanical and infectious PD complications, as
      need for pre-transplant nephrectomy and kidney transplantation, were considered.
      RESULTS: The two cohorts were similar in terms of age and body surface area. The
      median kidney size was not significantly different between PD and HD patients
      [19.1 cm (12.5-32.5) versus 16.5 cm (11.8-33.8), respectively, P = 0.13].
      However, we identified an increased number of PD patients with larger kidneys
      [(>25 cm) (27.8% on PD versus 7.7% on HD (P = 0.07)]. Neither cystic (infection
      or haemorrhage) nor mechanical complications (hernias and leaks) were different
      in PD or HD. Ten patients experienced PD-related peritonitis, mainly due to non
      enteric bacterial pathogens. The main reason for stopping PD and HD was
      transplantation. Six PD patients underwent nephrectomy in order to access the
      transplant programme. Among them, five were maintained on PD after surgical
      procedure with good adequacy dialysis criteria. CONCLUSIONS: We observed no
      deleterious impact of kidney size on outcomes on PD when compared with HD. A
      large kidney size in patients with PKD is not a contraindication to PD. Patients
      for whom a pre-transplant nephrectomy is mandatory can also safely opt for PD as
      a dialysis method.

PMID- 25852863
TI  - How good are we at managing acute kidney injury in hospital?
AB  - INTRODUCTION: Acute kidney injury (AKI) is a common clinical problem associated
      with adverse outcomes. This study identifies the incidence of AKI in two UK
      district general hospitals' without on-site renal services and assesses AKI
      management and level of nephrologist input. METHODS: The AKIN classification was
      used to identify 1020 AKI patients over 6 months. Data were collated on patient
      demographics, AKI management and referral to nephrology and intensive care
      services. Short/long-term renal outcomes were investigated. Patients were
      followed up for 14 months post-discharge. RESULTS: Incidence of hospital-based
      AKI was 6.4%. Mean patient age was 73 years. There was 28.1% acute in-hospital
      mortality with a further 21.6% 14-month mortality. Only 8.3% of patients were
      referred to nephrology services for in-hospital review, and only 8.1% had
      outpatient nephrology follow-up. Compliance with the AKI National Confidential
      Enquiry into Patient Outcomes and Deaths (NCEPOD) recommendations was poor with
      32.8% of patients having renal imaging and 15% of patients having acid-base
      status assessed. NCEPOD compliance improved with nephrology input. Patients
      referred to nephrology were likely to be younger with pre-existing CKD and severe
      AKI. 10.5% of AKI episodes were unrecognized. Forty percent of those with
      unrecognized AKI, (compared with 15% of recognized AKI) developed de novo or
      progression of pre-existing CKD. CONCLUSION: AKI in DGHs is mostly managed
      without nephrology input. There are significant shortcomings in AKI recognition
      and management in this setting. This is associated with poor mortality and long
      term CKD. This study supports a need to improve the teaching and training of
      front-line medical staff in identifying AKI. Additionally, implementation of AKI
      e-alert systems may encourage early recognition and provide a prompt for renal
      referral.

PMID- 25852864
TI  - Low serum sodium is associated with protein energy wasting and increased
      interdialytic weight gain in haemodialysis patients.
AB  - BACKGROUND: Low serum sodium (Na) has been associated with decreased body mass
      index and increased cardiovascular mortality in haemodialysis (HD) patients. We
      examined the relationship between serum Na and selected nutritional parameters of
      protein energy wasting that are not affected from the hydration status in a
      cohort of HD patients. METHODS: Triceps skinfold thickness (TSF), mid-arm
      circumference (MAC), mid-arm muscle circumference (MAMC), handgrip strength (HGS)
      and subjective global assessment (SGA) were assessed in maintenance HD patients
      using standard techniques. MAMC was calculated with the formula MAMC (cm) = MAC
      (cm) -3.142 * TSF cm. Pre-dialysis serum Na values from routine monthly
      laboratory measurements were averaged for the last 6 months prior to the
      nutritional assessment. RESULTS: Altogether 172 patients with anthropometric data
      were included in the final analysis. Mean age was 66 +/- 14, females 62 (36%) and
      diabetics 48 (28.9%). Patients with pre-dialysis serum Na below the mean value
      (136.2 mEq/L) had lower MAMC, HGS, SGA scores and albumin levels (23.50 +/- 3.16
      cm versus 24.58 +/- 3.71 cm, P = 0.048; 21.7 +/- 13.6 kg versus 28.0 +/- 12.4 kg,
      P = 0.030; 5.1 +/- 1.2 versus 5.7 +/- 1.0, P = 0.012 and 31.65 +/- 4.73 mg/L
      versus 32.25 +/- 3.91 mg/L, P = 0.022, respectively) and higher interdialytic
      weight gains. Pre-dialysis serum Na correlated positively with MAMC, handgrip and
      SGA (Pearson's correlation r = 0.165, P = 0.031, r = 0.237, P = 0.022 and r =
      0.195, P = 0.011, respectively). CONCLUSION: This study demonstrates that low
      serum sodium is associated with protein energy wasting and increased
      interdialytic weight gain in HD patients.

PMID- 25852866
TI  - The significance of tubuloreticular inclusions as a marker of systemic
      stimulation by interferons in a case of focal and segmental glomerulosclerosis
      associated with cytomegalovirus (CMV) infection.
AB  - The identification of large numbers of tubuloreticular inclusions (TRIs) in renal
      biopsies may be useful to raise diagnostic suspicion for certain clinical
      entities, particularly autoimmune diseases and viral infections. We report a case
      of a 65-year-old female with a 2-week history of malaise, massive proteinuria and
      lower extremity edema of acute onset. A renal biopsy was performed and the
      diagnosis of non-human immunodeficiency virus (HIV) tip-located, early focal
      segmental glomerulosclerosis (FSGS) was established. The electron microscopy
      examination was remarkable for the presence of diffuse foot process effacement
      and frequent TRIs in the endothelial cells of the glomerular capillary loops,
      endothelium of arterioles and cytoplasm of fibroblasts in the interstitium,
      highly suggestive of an underlying etiology. Patient clinical and laboratory
      workup revealed the absence of an autoimmune disease but the presence of a
      subclinical cytomegalovirus (CMV) infection. Therefore, we highlight that the
      identification of TRIs is a useful indicator of systemic interferon activity. In
      the present case, the unusual location of numerous TRIs was associated with a
      subclinical CMV infection in an immunocompetent patient. 

PMID- 25852865
TI  - Magnesium and FGF-23 are independent predictors of pulse pressure in pre-dialysis
      diabetic chronic kidney disease patients.
AB  - BACKGROUND: The aim of our study was to evaluate the relevance of magnesium and
      FGF-23 in terms of cardiovascular disease in a population of type 2 diabetic
      patients with nephropathy. METHODS: In a cross-sectional study, we included 80
      type 2 diabetic patients with chronic kidney disease (CKD) stages 2, 3 and 4. We
      analysed mineral metabolism, inflammation, oxidative stress and insulin
      resistance. Our population was divided into two groups according to their pulse
      pressure (PP) as follows: G-1 with PP < 50 mmHg (n = 34) and G-2 with PP >= 50
      mmHg (n = 46). RESULTS: We found that G-2 patients showed lower calcium (P =
      0.004), eGFR (P = 0.001), magnesium (P = 0.0001), osteocalcin (P = 0.0001) and
      25(OH)D3 (P = 0.001), and higher iPTH (P = 0.001), FGF-23 (P = 0.0001),
      malonaldehyde (P = 0.0001), interleukin 6 (P = 0.001) and HOMA-IR (P = 0.033). No
      differences were found between the two groups regarding age, duration of disease,
      haemoglobin, HgA1c and phosphorus. In a multivariate analysis, we found that FGF
      23 and magnesium independently influenced the PP [OR = 1.239 (1.001-2.082), P =
      0.039 and OR = 0.550 (0.305-0.727), P = 0.016, respectively]. CONCLUSIONS: In our
      diabetic population with early stages of CKD, FGF-23 as well as lower magnesium
      levels were significantly and independently associated with higher PP levels, an
      established marker of cardiovascular morbidity and mortality.

PMID- 25852867
TI  - Touch not the cat bot a glove*: ANCA-positive pauci-immune necrotizing
      glomerulonephritis secondary to Bartonella henselae.
AB  - A 36-year-old male presented with a secondary, but anti-neutrophil cytoplasmic
      antibody (ANCA) (proteinase-3) positive, vasculitis with renal insufficiency due
      to a pauci-immune necrotizing glomerulonephritis. An infective process was
      initially excluded by blood cultures and an echocardiogram prior to
      immunosuppression. The patient's condition failed to improve and re-evaluation
      confirmed infective endocarditis requiring valve replacement. Subsequent tissue
      cultures identified Bartonella henselae. Antibiotic treatment led to full
      resolution of physical, biochemical and immunological markers. This is the first
      case of B. henselae endocarditis-associated ANCA positivity with a pauci-immune
      glomerulonephritis. It demonstrates the importance of revisiting standard
      investigations in patients not improving expectantly on conventional therapy. 

PMID- 25852868
TI  - Sarcoid-like lung granulomas in a hemodialysis patient treated with a dipeptidyl
      peptidase-4 inhibitor.
AB  - It has been reported that the inhibition of dipeptidyl peptidase-4 (DPP-4)/CD26
      on T-cells by DPP-4 enzymatic inhibitors suppresses lymphocyte proliferation and
      reduces the production of various cytokines, including tumor necrosis factor
      (TNF)-alpha. A 72-year-old female with diabetic nephropathy on hemodialysis
      developed multiple lung nodules following the administration of vildagliptin. A
      biopsy demonstrated the histology of granulomas without caseous necrosis. The
      discontinuation of vildagliptin resulted in the disappearance of the granulomas
      within 4 months. As granulomatosis often develops in patients under anti-TNF
      alpha therapy, the accumulation of DPP-4 inhibitors or its metabolites is
      possibly linked to unrecognized complications, such as sarcoid-like lung
      granulomas. 

PMID- 25852869
TI  - Tumor-induced osteomalacia with normal systemic fibroblast growth factor-23
      level.
AB  - A 38-year-old man presenting with long bone/rib fractures was diagnosed with
      tumor-induced osteomalacia (TIO) caused by a giant cell tumor in the right foot
      with normal systemic fibroblast growth factor-23 (FGF23) levels. Multiple imaging
      modalities done initially and one year later were unable to localize the tumor.
      New-onset foot pain discovered a right foot mass with resolution of metabolic
      abnormalities post-surgery. Sampling from both femoral veins showed an elevated
      FGF23 value on the right side. This case is unique in that the patient had a
      normal systemic FGF23 level even with severe clinical manifestations of TIO. 

PMID- 25852870
TI  - Nephrotic-range proteinuria on interferon-beta treatment: immune-induced
      glomerulonephritis or other pathway?
AB  - We present a case report of a 37-year-old woman with multiple sclerosis (MS) who
      developed nephrotic-range proteinuria secondary to membrano proliferative
      glomerulonephritis (MPGN)-like disease with mesangial C3 deposition without
      evidence of immune-complex deposition in the context of long-term interferon-beta
      (IFN-beta) therapy. The complete remission of proteinuria following cessation of
      IFN-beta, strongly suggests causality. To our knowledge, this is the second case
      report of MPGN associated with IFN-beta use. This being the case, the negative
      immune screen, normal inflammatory markers and the absence of immune complex
      deposits would imply a different pathway to that previously suggested. 

PMID- 25852871
TI  - Rare complication of a dialysis catheter insertion.
AB  - Insertion of a dialysis catheter is a very common procedure in renal medicine,
      which is associated with one or more complications in ~15% of patients. Central
      venous catheter vascular erosion is a rare but serious complication, the
      incidence appears to be between 0.4 and 1% which can be difficult to diagnose,
      leading to increased morbidity and mortality. We report a case of a persistent
      left-sided superior vena cava (PLSVC) and a possible central venous catheter
      vascular erosion following insertion of a left-sided internal jugular dialysis
      catheter. We discuss the mechanisms, diagnosis and measures to limit vascular
      erosion and also briefly discuss PLSVC. 

PMID- 25852872
TI  - Membrane and centrifugal therapeutic plasma exchange: practical difficulties in
      anticoagulating the extracorporeal circuit.
AB  - Therapeutic plasma exchange (TPE) is a well-established treatment modality for
      nephrology patients, using two conventional methods: membrane (mTPE) or
      centrifugal TPE (cTPE). Although the efficacy of both treatments has been
      described, there are few reports that compare these methodologies. Here we
      describe three nephrology patients who were treated with both mTPE and cTPE. The
      mTPE method, but not the cTPE method, was associated with persistent difficulty
      anticoagulating the extracorporeal circuit in all three patients. In mTPE
      procedures, the doses of heparin bolus and infusion rate were important
      determinants of whether the circuit clotted. With a heparin bolus at or below
      2000 IU, clotting occurred in 67% of treatments, dropping to 25% with a bolus of
      >2000 IU. Likewise, a heparin infusion rate during the procedure was indicative
      of clotting. With a maintenance infusion of <2000 IU/h, most circuits clotted. No
      clotting was observed during cTPE procedures using acid citrate dextrose formula
      A solution as an anticoagulant of the extracorporeal circuit. Overall,
      difficulties maintaining the extracorporeal circuit in mTPE required the use of
      additional disposable sets, high doses of heparin and nursing time. In addition,
      mTPE procedures took longer to perform than cTPE. 

PMID- 25852873
TI  - Hemodialysis-associated endovascular device infection.

PMID- 25852874
TI  - Ganciclovir-resistant cytomegalovirus infection in renal transplantation.

PMID- 25852875
TI  - Hypomagnesemia and hypokalemia: a successful oral therapeutic approach after 16
      years of potassium and magnesium intravenous replacement therapy.

PMID- 25852876
TI  - Nephrocalcinosis in primary Sjogren's syndrome.

PMID- 25852877
TI  - Colchicine-resistant familial Mediterranean fever in a renal transplantation
      patient: successful treatment with anakinra.

PMID- 25852878
TI  - Acute interstitial nephritis following viper bite: a rare association.

PMID- 25852879
TI  - Influenza and pneumococcal vaccinations in dialysis patients.

PMID- 25852880
TI  - The 20th anniversary of BANTAO (Balkan Cities Association of Nephrology,
      Dialysis, Transplantation and Artificial Organs).

PMID- 25852882
TI  - Insulin for the treatment of hyperkalemia: a double-edged sword?

PMID- 25852881
TI  - Renal replacement therapy in Europe: a summary of the 2011 ERA-EDTA Registry
      Annual Report.
AB  - BACKGROUND: This article provides a summary of the 2011 ERA-EDTA Registry Annual
      Report (available at www.era-edta-reg.org). METHODS: Data on renal replacement
      therapy (RRT) for end-stage renal disease (ESRD) from national and regional renal
      registries in 30 countries in Europe and bordering the Mediterranean Sea were
      used. From 27 registries, individual patient data were received, whereas 17
      registries contributed data in aggregated form. We present the incidence and
      prevalence of RRT, and renal transplant rates in 2011. In addition, survival
      probabilities and expected remaining lifetimes were calculated for those
      registries providing individual patient data. RESULTS: The overall unadjusted
      incidence rate of RRT in 2011 among all registries reporting to the ERA-EDTA
      Registry was 117 per million population (pmp) (n = 71.631). Incidence rates
      varied from 24 pmp in Ukraine to 238 pmp in Turkey. The overall unadjusted
      prevalence of RRT for ESRD on 31 December 2011 was 692 pmp (n = 425 824). The
      highest prevalence was reported by Portugal (1662 pmp) and the lowest by Ukraine
      (131 pmp). Among all registries, a total of 22 814 renal transplantations were
      performed (37 pmp). The highest overall transplant rate was reported from Spain,
      Cantabria (81 pmp), whereas the highest rate of living donor transplants was
      reported from Turkey (39 pmp). For patients who started RRT between 2002 and
      2006, the unadjusted 5-year patient survival on RRT was 46.8% [95% confidence
      interval (CI) 46.6-47.0], and on dialysis 39.3% (95% CI 39.2-39.4). The
      unadjusted 5-year patient survival after the first renal transplantation
      performed between 2002 and 2006 was 86.7% (95% CI 86.2-87.2) for kidneys from
      deceased donors and 94.3% (95% CI 93.6-95.0) for kidneys from living donors.

PMID- 25852883
TI  - Central vasopressin: dendritic and axonal secretion and renal actions.

PMID- 25852884
TI  - Hypoglycemia in the treatment of hyperkalemia with insulin in patients with end
      stage renal disease.
AB  - BACKGROUND: Hypoglycemia is common in patients with end-stage renal disease
      (ESRD). We identified the incidence and timing of hypoglycemia and its risk
      factors in hospitalized patients with ESRD after the treatment of hyperkalemia
      with insulin. METHODS: We conducted a retrospective study of all hospitalized
      adult patients treated with hemodialysis who received intravenous insulin to
      treat hyperkalemia between 1 January 2011 and 31 December 2011. We identified
      patients who became hypoglycemic [blood glucose <3.3 mmol/L (60 mg/dL)] after
      insulin administration. RESULTS: Two hundred and twenty-one episodes of
      hyperkalemia were treated with insulin, resulting in 29 episodes of hypoglycemia
      (13%). Factors associated with a higher risk of hypoglycemia included no prior
      diagnosis of diabetes [odds ratio (OR) 2.3, 95% confidence interval (CI) 1.0-5.1,
      P = 0.05], no use of diabetes medication prior to admission [OR 3.6, 95% CI 1.2
      10.7, P = 0.02] and a lower pretreatment glucose level [mean 5.8 +/- 0.7 mmol/L
      (104 +/- 12 mg/dL) versus 9.0 +/- 0.6 mmol/L (162 +/- 11 mg/dL), P = 0.04].
      Hypoglycemia occurred at a median of 2 h after insulin administration and
      persisted for a median of 2 h. CONCLUSIONS: The treatment of hyperkalemia with
      insulin in hospitalized patients with ESRD may be complicated by hypoglycemia.
      Patients with a history of diabetes are less susceptible to this complication.
      Our study supports the use of a protocol to provide dextrose support and blood
      glucose monitoring for at least 3 h after insulin treatment of hyperkalemia.

PMID- 25852885
TI  - Multiple kidney cysts in thin basement membrane disease with proteinuria and
      kidney function impairment.
AB  - BACKGROUND: Some patients with thin basement membrane disease (TBMD) develop
      proteinuria, hypertension and different degrees of CKD, besides the persistent
      microhaematuria characteristic of the disease. Little is known about factors
      associated with this unfavourable outcome. METHODS: We reviewed clinical,
      pathological and radiological features of 32 patients with biopsy-proven TBMD.
      Patients were divided in two groups: those with persistent normal kidney function
      and negative or minimal proteinuria (n = 16) and those with persistent
      proteinuria >0.5 g/day (n = 16). RESULTS: Patients with proteinuria had a worse
      kidney function at baseline than those with negative proteinuria. Global or
      segmental glomerulosclerosis, together with interstitial fibrosis, was found in
      37% of patients with proteinuria. All proteinuric patients were treated with
      renin-angiotensin system blockers. At the end of follow-up (198 months in
      proteinuric patients and 210 months in patients with negative proteinuria) the
      prevalence of hypertension was 68% in proteinuric patients (12% at baseline),
      compared with 12 and 6%, respectively, in non-proteinuric patients. A slow
      decline of renal function was observed in proteinuric patients, although no
      patient developed end-stage kidney disease. Ultrasound studies showed bilateral
      kidney cysts in nine patients (56%) with proteinuria. Cysts were bilateral and
      countless in six patients, and bilateral but with a limited number of cysts in
      the three remaining patients. No cysts were found in patients with negative
      proteinuria. CONCLUSIONS: Some patients with TBMD develop hypertension,
      proteinuria and CKD. Multiple bilateral kidney cysts were found in a majority
      (56%) of these patients. Further studies are needed to investigate the
      pathogenesis and the influence on long-term outcome of this TBMD-associated
      multiple kidney cysts.

PMID- 25852887
TI  - Minimally invasive fluoroscopic percutaneous peritoneal dialysis catheter
      salvage.
AB  - BACKGROUND: Peritoneal dialysis catheter (PDC) dysfunction can often be treated
      fluoroscopically by manipulation with wire, balloon or stiff stylet, saving
      surgical intervention for refractory cases. We describe an enhanced percutaneous
      approach to PDC salvage that can lead to a more definitive intervention and
      salvage for cases refractory to fluoroscopic manipulation. METHODS: In five cases
      of PD catheter malfunction, the deep cuff was dissected free after a 0.035
      hydrophilic wire was passed into the peritoneum through the PDC. Only the
      intraperitoneal portion of the PDC was explanted. The PDC was cleared of
      obstruction and omentum. The intraperitoneal portion of the PDC was reimplanted
      over wire via a peel-away sheath and the deep cuff sutured. RESULTS: Omental
      entrapment was present in three of five patients and fibrin occlusion in four of
      the five cases. All catheters were repaired successfully by the described
      technique. Post procedure, 3-5 days of lower volume, recumbent PD exchanges were
      performed prior to full-dose PD. No perioperative complications or leaks were
      noted. All PDCs were patent at 6 months. One patient required laparoscopy for
      recurrent omental wrapping 3 months post intervention. CONCLUSIONS: PDC salvage
      in this manner is a cost-effective alternative to laparoscopic repair of PDCs
      failing catheter manipulation. The infection barrier afforded by the original
      superficial cuff and subcutaneous tunnel is maintained. PD can be resumed
      immediately. Only refractory cases need laparoscopy. This procedure allows for a
      more definitive correction of catheter migration and obstruction, avoids
      placement of a new PDC or temporary hemodialysis, is cost-effective and expands
      percutaneous options for dysfunctional PD catheters.

PMID- 25852886
TI  - Falls among hemodialysis patients: potential opportunities for prevention?
AB  - BACKGROUND: Falls among patients undergoing maintenance hemodialysis (HD) have
      significant consequences for quality of life and functional independence,
      morbidity, healthcare utilization and even mortality, but studies on the etiology
      of falls within large HD cohorts are limited. METHODS: Falls during the past 12
      months were ascertained for a prevalent multi-center HD cohort (n = 762) aged 20
      92 years, and associations with demographic and treatment characteristics,
      comorbidities, cognitive function, prescribed medications, balance tests, frailty
      and depressive symptoms were assessed. RESULTS: Falls were sustained by 28.4% of
      participants. In multivariable-adjusted analyses, participants classified as
      frail were over two times more likely to report falls [odds ratio (OR): 2.39, 95%
      confidence interval (CI): 1.22-4.71, P = 0.01], and participants with a CES-D
      score 18+ and/or prescribed antidepressants were over 80% more likely to be
      fallers (OR: 1.83, 95% CI: 1.23-2.74, P = 0.003) than were participants with a
      CES-D score <18 and no prescribed antidepressants. CONCLUSIONS: Frailty and
      depressed mood, factors that are potentially modifiable, are prominently
      associated with falls.

PMID- 25852888
TI  - Distinct cytokine mRNA expression pattern in immunoglobulin G4-related kidney
      disease associated with renal cell carcinoma.
AB  - We treated a 61-year-old man with immunoglobulin (Ig)G4-related kidney disease
      (IgG4-RKD). He had a history of allergic diseases and an allergic reaction and
      had received a diagnosis of autoimmune pancreatitis (AIP). He had also received a
      diagnosis of renal cell carcinoma (RCC) and had undergone segmental resection of
      the left kidney at 59 years of age. His serum amylase level and number of
      peripheral eosinophils increased after RCC development. We hypothesized that the
      RCC may have induced AIP and IgG4-RKD and we therefore examined the excised RCC
      tissue; typical findings of IgG4-RKD associated with RCC were recognized. We next
      evaluated the mRNA expression of cytokines in the excised tissues of this case
      and ten other ordinary RCC cases. In all cases, notable levels of IL-10 mRNA and
      high levels of TGF-beta mRNA were seen. Although prominent differences were not
      observed in the mRNA expression of Th1, Th17 and Treg cytokines in all cases, the
      present case alone showed increased production of the Th2 cytokines IL-4 and IL
      5, which were not detected in ordinary RCC cases. Although the mechanism
      underlying IgG4-RKD development has not yet been determined, Th2 and Treg cells
      are thought to play a prominent role in the pathogenesis. It is therefore likely
      that in this case, the association of these two diseases was not coincidental,
      and a distinct immune response against RCC may trigger IgG4-RKD development. 

PMID- 25852889
TI  - Delta-He: a novel marker of inflammation predicting mortality and ESA response in
      peritoneal dialysis patients.
AB  - BACKGROUND: Inflammation impairs erythropoiesis, iron availability and is
      associated with a higher mortality risk in patients with end-stage renal disease.
      We studied the associations between Delta-He [the difference between the
      reticulocyte haemoglobin content (Ret-He) and erythrocyte haemoglobin content], a
      suggested marker of iron availability, and markers of inflammation, iron status,
      response to erythropoiesis-stimulating agents (ESAs) and mortality in prevalent
      peritoneal dialysis (PD) patients. METHODS: Eighty-two PD patients were followed
      weekly for 12 weeks with an additional follow-up of 36 months. Delta-He, Ret-He
      and high-sensitivity C-reactive protein (hs-CRP) were measured weekly and
      interleukin-6 (IL-6) and iron markers every fourth week. Mortality risk was
      assessed by Cox proportional hazards model adjusting for potential confounding
      factors. The relationships between ESA response, inflammatory markers, iron
      markers and Delta-He were evaluated in the PD patients. The relationship between
      Delta-He and iron markers was analysed in 87 healthy subjects. RESULTS: Delta-He
      correlated with IL-6 (rho = 0.48, P < 0.001), hs-CRP (rho = 0.36, P < 0.001) and
      ESA hyporesponsivess index (EHRI; rho = -0.44, P < 0.001) in the PD patients.
      Delta-He did not correlate with iron markers in PD patients nor in healthy
      subjects. The mean Delta-He levels were significantly different between the
      tertiles of EHRI (P < 0.01). Delta-He was associated with all-cause mortality
      risk in PD patients after adjusting for age, gender, hs-CRP, comorbidity and
      nutritional status [OR 0.70 (0.51-0.96), P < 0.05]. CONCLUSIONS: Delta-He
      independently predicts all-cause mortality in PD patients after adjusting for
      potential confounders and is a predictor of ESA response in PD patients.

PMID- 25852890
TI  - Two novel mutations of the CLDN16 gene cause familial hypomagnesaemia with
      hypercalciuria and nephrocalcinosis.
AB  - Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis is an autosomal
      recessive disease caused by mutations in the CLDN16 or CLDN19 genes, which encode
      tight junction-associated proteins, claudin-16 and -19. The resultant tubulopathy
      leads to urinary loss of Mg(2+) and Ca(2+), with subsequent nephrocalcinosis and
      end-stage renal disease (ESRD). An 18-year-old boy presented with chronic kidney
      disease and proteinuria, as well as hypomagnesaemia, hypercalciuria and
      nephrocalcinosis. A kidney biopsy revealed tubular atrophy, interstitial fibrosis
      and segmental sclerosis of some glomeruli. Two novel mutations in the CLDN16 gene
      were identified: c.340C>T (nonsense) and c.427+5G>A (splice site). The patient
      reached ESRD at 23 and benefited from kidney transplantation. 

PMID- 25852891
TI  - Allograft adenovirus nephritis.
AB  - We present an uncommon case of allograft adenovirus tubulointerstitial nephritis
      in a 63-year-old male 6 weeks following cadaveric renal transplantation for end
      stage renal failure secondary to hypertensive nephrosclerosis. The patient
      presented with acute onset of fevers, dysuria, haematuria and diarrhoea with
      acute graft dysfunction. A renal biopsy demonstrated necrotizing
      tubulointerstitial nephritis with viral cytopathic changes and no evidence of
      rejection. Adenovirus was identified as the pathogen. Treatment involved the
      reduction in the patient's usual immunosuppression, intravenous immunoglobulin,
      piperacillin-tazobactam and ganciclovir. We present the clinical and pathological
      findings of necrotizing adenoviral nephropathy, highlighting the importance of
      considering this diagnosis in renal transplant recipients presenting with
      interstitial nephritis in the setting of a systemic illness. 

PMID- 25852892
TI  - Sustained complete remission of steroid- and cyclophosphamide-resistant minimal
      change disease with a single course of rituximab therapy.
AB  - We report a case of steroid- and cyclophosphamide-resistant nephrotic syndrome
      secondary to minimal-change disease occurring in an otherwise healthy 19-year-old
      female, responding rapidly to two doses of rituximab therapy. Complete disease
      remission has been sustained up to last follow-up (32 months) despite CD19
      recovery. Literature review suggests emerging evidence that rituximab may have a
      role to play in recurrent and/or refractory minimal-change disease. 

PMID- 25852893
TI  - Crystalloid glomerulopathy in monoclonal gammopathy of renal significance (MGRS).
AB  - We report a case of monoclonal gammopathy of renal significance in a 63-year-old
      man who presented with nephrotic-range proteinuria and renal insufficiency. The
      kidney biopsy showed a membranoproliferative glomerulonephritis pattern with
      extensive crystalloid deposits in the glomerular capillary endothelial cells and
      very few in the tubular epithelial cells. The immunoperoxidase staining showed
      kappa light chain restriction. Subsequently, the bone marrow showed 6% plasma
      cells which confirmed the diagnosis of monoclonal gammopathy of renal
      significance. He responded well to bortezomib treatment with resolution of the
      nephrotic syndrome and normalization of renal function after 7 months. 

PMID- 25852894
TI  - Metabolic acidosis-induced hypercalcemia in an azotemic patient with primary
      hyperparathyroidism.
AB  - A 58-year-old man with Stage 3b chronic kidney disease and primary
      hyperparathyroidism treated with cinacalcet was admitted for acute cholecystitis.
      A cholecystostomy tube was placed, estimated glomerular filtration rate
      decreased, metabolic acidosis developed and ionized calcium increased from 1.33
      to 1.76 mM despite cinacalcet administration. A sodium bicarbonate infusion
      corrected the metabolic acidosis restoring ionized calcium to normal despite no
      improvement in renal function. The correlation between the increase in serum
      bicarbonate and decrease in ionized calcium was r = -0.93, P < 0.001. In summary,
      severe hypercalcemia was attributable to metabolic acidosis increasing calcium
      efflux from bone while renal failure decreased the capacity to excrete calcium. 

PMID- 25852895
TI  - Steroid-resistant nephrotic syndrome with mutations in NPHS2 (podocin): report
      from a three-generation family.
AB  - Genetic causes of steroid-resistant nephrotic syndrome are being increasingly
      recognized. Mutations in NPHS2, which encodes the glomerular protein podocin,
      account for up to 17% of sporadic and 40% of familial cases, where they display
      an autosomal-recessive pattern of inheritance. This report describes a non
      consanguineous family with three generations of individuals who are either
      compound heterozygotes for mutations in NPHS2 or who have inherited a mutation
      and a non-neutral polymorphism (R229Q). As well as providing an aetiological
      explanation, identifying pathogenic mutations and considering genotype-phenotype
      correlations can provide prognostic information and lead to changes in genetic
      counselling and management. 

PMID- 25852896
TI  - A severe phenotype of Gitelman syndrome with increased prostaglandin excretion
      and favorable response to indomethacin.
AB  - Our understanding of Gitelman syndrome (GS) and Bartter syndrome has continued to
      evolve with the use of genetic testing to more precisely define the tubular
      defects responsible. GS is caused by mutations in the SLC12A3 gene encoding the
      Na(+)-Cl(-) co-transporter of the distal convoluted tubule (NCCT) and tends to be
      associated with a milder salt-losing phenotype. We describe two female siblings
      presenting in infancy with a severe salt-losing tubulopathy and failure to thrive
      due to compound heterozygous mutations in the SLC12A3 gene encoding the NCCT.
      Both children were treated with indomethacin resulting in improved linear growth
      and polyuria. Some atypical biochemical findings in our cases are discussed
      including raised urinary prostaglandin (PGE2) excretion that normalized with
      intravenous fluid repletion. 

PMID- 25852897
TI  - Renal-limited thrombotic microangiopathy and acute interstitial nephritis with a
      single dose of quinine.
AB  - Quinine has been reported to cause acute kidney injury by various mechanisms. The
      response to quinine can result in a spectrum of problems ranging from isolated
      thrombocytopenia to thrombotic microangiopathy (TMA) to disseminated
      intravascular coagulation. Quinine has also been reported to cause acute
      interstitial nephritis (AIN). We report an unusual presentation where both of
      these entities of renal-limited TMA and AIN were precipitated by a single dose of
      quinine. 

PMID- 25852898
TI  - Fever of unknown origin in a haemodialysis patient: a late diagnosis requiring a
      novel treatment.

PMID- 25852899
TI  - A day in the zoo.

PMID- 25852900
TI  - High anion gap metabolic acidosis: use the proper acronym, discard the red
      herrings and thou shall find the culprit.

PMID- 25852901
TI  - Cyclophosphamide-induced toxic epidermal necrolysis: vigilance needed.

PMID- 25852902
TI  - Nutcracker phenomenon in IgA nephropathy.

PMID- 25852903
TI  - Adult orthostatic proteinuria.

PMID- 25852904
TI  - Trimethylamine generation in patients receiving hemodialysis treated with l
      carnitine.

PMID- 25852905
TI  - Renal replacement therapy in Ukraine: epidemiology and international comparisons.
AB  - BACKGROUND: Little is known about the status of renal replacement therapy (RRT)
      in the post-Soviet countries. We therefore investigated the epidemiology and
      treatment outcomes of RRT in Ukrainian patients and put the results into an
      international perspective. METHODS: Data from the Ukrainian National Renal
      Registry for patients on RRT between 1 January 2010 and 31 December 2012 were
      selected. We calculated the incidence and prevalence of RRT per million
      population (pmp) and the 3-, 12- and 24-month patient survival using the Kaplan
      Meier method and Cox regression. RESULTS: There were 5985 prevalent patients on
      RRT on 31 December 2012 (131.2 pmp). Mean age was 46.5 +/- 13.8 years, 56% men
      and 74% received haemodialysis (HD), while peritoneal dialysis and kidney
      transplantation both represented 13%. The most common cause of end-stage renal
      disease was glomerulonephritis (51%), while only 12% had diabetes. In 2012, 1129
      patients started dialysis (incidence 24.8 pmp), with 80% on HD. Mean age was 48
      +/- 14 years, 58% men and 20% had diabetes. Three, 12- and 24-month patient
      survival on dialysis was 95.1%, 86.0% and 76.4%, respectively. The transplant
      rate in 2012 was 2.1 pmp. CONCLUSIONS: The incidence and prevalence of RRT and
      the transplantation rate in Ukraine are among the lowest in Europe, suggesting
      that the need for RRT is not being met. Strategies to reduce the RRT deficit
      include the development and improvement of transplantation and home-based
      dialysis programmes. Further evaluation of the quality of Ukrainian RRT care is
      needed.

PMID- 25852906
TI  - The eye: a window on kidney diseases.

PMID- 25852907
TI  - Erdheim-Chester disease: from palliative care to targeted treatment.
AB  - Erdheim-Chester disease (ECD) is a life-threatening multi-systemic non-Langerhans
      histiocytosis with cardiovascular complications as the leading cause of death.
      ECD affects the kidneys in up to 30% of cases, with fibrotic tissue deposition in
      the perirenal fat and renal hilum. Diagnosis is usually based on histological
      analysis of the pathologic tissue, which typically shows xanthogranulomatous
      infiltrates of foamy CD68+/CD1a- histiocytes surrounded by fibrosis. A consistent
      percentage of patients affected by ECD develop renal failure and hypertension as
      a consequence of renal artery stenosis and hydronephrosis. These conditions have
      been generally treated with the placement of stents and nephrostomies that
      frequently led to disappointing outcomes. Before the introduction of interferon
      alpha (IFNalpha) treatment, the mortality rate was as high as 57% in the long
      term. Recent studies have granted new insights into the pathogenesis of ECD,
      which seems to bear a dual component of clonal and inflammatory disease. These
      advances led to use specific therapies targeting either the oncogenes
      (BRAF(V600E)) or the effectors of the immune response implicated in ECD (IL-1,
      TNFalpha). Drugs such as anakinra (recombinant human IL-1 receptor antagonist),
      infliximab (monoclonal antibody against TNFalpha) and vemurafenib (inhibitor of
      mutant BRAF) showed promising results in small single-centre series. Although
      larger trials will be needed to address the impact of these drugs on ECD
      prognosis and to select the most effective treatment, targeted therapies hold the
      premises to drastically change the outcome of this condition. 

PMID- 25852908
TI  - Dent-Wrong disease and other rare causes of the Fanconi syndrome.
AB  - Dent-Wrong disease, an X-linked recessive disorder of the proximal tubules,
      presents with hypercalciuria, nephrocalcinosis, nephrolithiasis, renal
      insufficiency, low-molecular-weight proteinuria, rickets and/or osteomalacia.
      Dent and Friedman initially characterized the disorder in 1964 following studies
      of two patients with rickets who presented with hypercalciuria,
      hyperphosphaturia, proteinuria and aminoaciduria. Since then, extensive
      investigation identified two genetic mutations (CLCN5 and OCRL1) to be associated
      with Dent-Wrong disease. Clinical features supported by laboratory findings
      consistent with proximal tubule dysfunction help diagnose Dent-Wrong disease.
      Genetic analysis supports the diagnosis; however, these two genes can be normal
      in a small subset of patients. The differential diagnosis includes other forms of
      the Fanconi syndrome, which can be hereditary or acquired (e.g. those related to
      exposure to exogenous substances). Treatment is supportive with special attention
      to the prevention of nephrolithiasis and treatment of hypercalciuria. We review
      the rare forms of Fanconi syndrome with special attention to Dent-Wrong disease. 

PMID- 25852909
TI  - Urinary angiotensinogen as a potential biomarker of diabetic nephropathy.
AB  - BACKGROUND: Activation of the renin-angiotensin-aldosterone system (RAAS) is an
      important mediator of diabetic nephropathy. Urinary angiotensinogen, a novel
      biomarker of the intrarenal RAAS, is associated with progressive kidney injury.
      In this study, the authors investigated the determinants of urinary
      angiotensinogen and its associations with staging of diabetic nephropathy.
      METHODS: Random urine samples were collected from the patients with type 2
      diabetes with normoalbuminuria (n = 52), microalbuminuria (n = 52) and
      macroalbuminuria (n = 51) for the measurement of angiotensinogen by sensitive and
      specific ELISAs. Control samples were collected from healthy volunteers (n = 20)
      who had normal albuminuria and renal function. RESULTS: Urinary angiotensinogen
      was higher in microalbuminuric and macroalbuminuric diabetes than in controls
      [63.44 (interquartile range, IQR: 22.08, 174.8) versus 398.38 (IQR: 205.03,
      673.68) versus 9.12 (IQR: 3.76, 23.82) ng/mg creatinine, respectively, P <
      0.001]. In diabetes with normoalbuminuria, urinary angiotensinogen was also
      higher than in controls [16.42 (IQR: 7.69, 34.71) versus 9.12 (IQR: 3.76, 23.82)
      ng/mg creatinine, P = 0.047]. The performance of the biomarker in differentiating
      each stage of type 2 diabetes from controls was illustrated by receiver-operating
      characteristic curves. The areas under the curve for the diagnosis of established
      normoalbuminuric, microalbuminuric and macroalbuminuric type 2 diabetes using
      urine angiotensinogen (ng/mg creatinine) were 0.62 (95% CI: 0.48-0.77), 0.85 (95%
      CI: 0.76-0.94) and 0.96 (95% CI: 0.92-1.00), respectively. In addition, the cut
      off levels were 9.30 ng/mg (sensitivity 65.4%, specificity 55.0%), 12.32 ng/mg
      (sensitivity 55.8%, specificity 65.0%) and 17.44 ng/mg (sensitivity 44.2%,
      specificity 70.0%), respectively, for distinguishing normoalbuminuric type 2
      diabetes from healthy controls. CONCLUSIONS: The authors propose that
      angiotensinogen could be one of the potential urinary biomarkers for diagnosis in
      established diabetic nephropathy. It appeared even before the significant
      albuminuria in diabetic nephropathy. It might be useful as an early biomarker of
      activation of the renin-angiotensin system in diabetic nephropathy.

PMID- 25852910
TI  - Measuring pain in patients undergoing hemodialysis: a review of pain assessment
      tools.
AB  - BACKGROUND: Patients undergoing hemodialysis frequently report pain with
      multifactorial causes, not limited to that experienced directly from hemodialysis
      treatment. Their pain may be nociceptive, neuropathic, somatic or visceral in
      nature. Despite this, pain in this population remains under-recognized and under
      treated. Although several tools have been used to measure pain in patients
      undergoing hemodialysis as reported in the literature, none of them have been
      validated specifically in this population. The objective for this review was to
      compare and contrast these pain assessment tools and discuss their clinical
      utility in this patient population. METHODS: To identify pain assessment tools
      studied in patients undergoing hemodialysis, a literature search was performed in
      PubMed and Medline. An expert panel of dialysis and pain clinicians reviewed each
      tool. Each pain assessment tool was assessed on how it is administered and
      scored, its psychometric properties such as reliability, validity and
      responsiveness to change, and its clinical utility in a hemodialysis population.
      Brief Pain Inventory, McGill Pain Questionnaire, Pain Management Index, Edmonton
      Symptom Assessment System, Visual Analogue Scale and Faces Pain Scale were
      evaluated and compared. RESULTS: This assessment will help clinicians practicing
      in nephrology to determine which of these pain assessment tools is best suited
      for use in their individual clinical practice.

PMID- 25852911
TI  - Three-month variation of plasma pentraxin 3 compared with C-reactive protein,
      albumin and homocysteine levels in haemodialysis patients.
AB  - BACKGROUND: Inflammatory markers vary considerably over time in haemodialysis
      (HD) patients, yet the variability is poorly defined. The aim of the study was to
      assess changes of plasma levels of pentraxin-3 (PTX-3), C-reactive protein (CRP),
      albumin and homocysteine (Hcy) over 3 months and the association between the
      changes in these biomarkers and mortality. METHODS: In 188 prevalent HD patients,
      inflammatory markers were measured at inclusion and after 3 months. Mortality was
      recorded during a median follow-up of 41 months. The changes of the biomarker
      levels were categorized according to change in tertile for the specific
      biomarker. The variation was calculated as the intra-class correlation (ICC).
      Mortality was analysed by Kaplan-Meier and Cox proportional hazards model. The
      predictive strength was calculated for single measurements and for the variation
      of each inflammatory marker. RESULTS: The intra-individual variation (low ICC)
      was largest for PTX-3 [ICC 0.44; 95% confidence interval (CI): 0.33-0.55],
      albumin (ICC 0.58; 95% CI: 0.49-0.67) and CRP (ICC 0.59; 95% CI: 0.51-0.68) and
      lowest for Hcy (ICC 0.81; 95% CI: 0.77-0.86). During follow-up, 88 patients died.
      CONCLUSIONS: PTX-3 measurements are less stable and show higher variation within
      patients than CRP, albumin and Hcy. Persistently elevated PTX-3 levels are
      associated with high mortality. Moreover, in multivariate logistic regression we
      found that stable high PTX-3 adds to the mortality risk, even after inclusion of
      clinical factors and the three other biomarkers. The associations of decreasing
      albumin levels as well as low Hcy levels with worse outcome reflect protein
      energy wasting.

PMID- 25852912
TI  - Acute kidney injury due to decompression illness.
AB  - Decompression illness is a rare but serious complication of diving caused by
      intravascular or extravascular gas bubble formation. We report the first case of
      acute kidney injury in a 27-year-old diver following three rapid ascents. He
      presented with transient neurological symptoms and abdominal pain followed by
      rapidly progressive acute kidney injury (creatinine peak 1210 umol/L) due to
      arterial air emboli. He received supportive care and 100% oxygen followed by
      hyperbaric therapy and recovered fully. Arterial air emboli caused by rapid
      decompression can affect multiple organs including the kidneys. Early transfer to
      a hyperbaric unit is important as complications may present delayed. 

PMID- 25852913
TI  - Sarcoidosis presenting as severe renin-dependent hypertension due to kidney
      vascular injury.
AB  - Renal sarcoidosis embraces a wide variety of clinical patterns. Renal vascular
      involvement has seldom been reported and usually in the setting of systemic
      vasculitis. We report the case of a 22-year-old patient in whom inaugural
      manifestation of renal sarcoidosis consisted of severe hypertension associated
      with bilateral perfusion defects and tumour-like nodules. In the setting of renal
      sarcoidosis, our case suggests that renin-dependant hypertension may arise from
      renal ischaemia as a result of extrinsic compression of kidney blood vessels due
      to severe granulomatous inflammation. 

PMID- 25852914
TI  - Hypotension-induced blindness in haemodialysis patients.
AB  - Hypotension is a commonly encountered complication in haemodialysis patients and
      is a significant cause of morbidity and mortality. Bilateral visual loss in
      dialysis induced hypotension remains poorly recognized as a complication by both
      renal physicians and ophthalmologists. We report 2 cases of patients on renal
      dialysis who suffered severe longstanding hypotension with bilateral non
      arteritic anterior ischaemic optic neuropathy. Both patients experienced
      bilateral loss of vision over a short time period. We feel that physicians must
      be aware of patients complaining of painless visual loss in this high risk group,
      as control of blood pressure may be the most important factor in prevention of
      this visually devastating condition. 

PMID- 25852915
TI  - Membranoproliferative glomerulonephritis and Pott's disease.
AB  - The reports of glomerular lesions of kidney due to tuberculosis are sparse. A 48
      year-old gentleman, presented with swelling of feet of 3 months duration. As he
      had renal impairment, proteinuria and normal-sized kidneys, he was subjected to
      renal biopsy. The light microscopy and immunofluorescence revealed the diagnosis
      was membrano-proliferative glomerulonephritis. During hospital stay, the patient
      complained fever and stiffness at thoracic spine. The MRI of thoraco-lumbo-sacral
      spine revealed paravertebral abscess at D11-D12. The pus aspirated was positive
      for Mycobacterium tuberculosis. He was started on anti-tuberculous medication.
      After 8 weeks of therapy, the serum creatinine was 1.5 mg/dL and 24 h urine
      protein 250 mg. 

PMID- 25852916
TI  - Neurofibromatosis type 1-associated hypertension secondary to coarctation of the
      thoracic aorta.
AB  - Neurofibromatosis type 1 (NF-1), also known as von Recklinghausen's disease, is
      an autosomal dominant genetic disorder. NF-I vasculopathy has been used to
      describe various vascular malformations associated with NF-1. Secondary
      hypertension related to NF-1 vasculopathy has been reported because of renal
      artery stenosis, coarctation of the abdominal aorta and other vascular lesions;
      however, coarctation of the thoracic aorta has seldom been reported. We report
      the first case, to our knowledge, of isolated coarctation of thoracic aorta in a
      pregnant female with NF-1. Healthcare providers caring for patients with NF-1
      should be aware of associated vascular complications. 

PMID- 25852917
TI  - Long-term outcome of kidney transplantation in a patient with coexisting
      lipoprotein glomerulopathy and fibrillary glomerulonephritis.
AB  - Both lipoprotein glomerulopathy (LPG) and fibrillary glomerulonephritis (FGN) are
      rare causes of end-stage renal disease (ESRD), and the literature concerning the
      outcome of kidney transplant in patients with LPG or FGN is scarce. We report a
      patient who suffered from ESRD with coexisting FGN and LPG and received deceased
      kidney transplant >10 years ago did not reveal any clinical features of disease
      recurrence during follow-up. Our case shows that the prognosis of patients with
      LPG component who received kidney transplant can be good. Kidney transplantation
      remains a viable therapeutic option for patients with ESRD secondary to FGN with
      LPG. 

PMID- 25852918
TI  - Necrotizing pancreatitis due to hypercalcemia in a hemodialysis patient with
      pica.
AB  - Pica refers to the persistent, compulsive craving for and ingestion of nonfood
      items and certain food items. Pica is quite common among dialysis patients. The
      nutrient composition of some of the substances ingested may contribute to severe
      metabolic and mineral disturbances and other serious medical complications. We
      report the first case of a hemodialysis patient with chalk pica associated
      hypercalcemia who developed acute necrotizing pancreatitis. Hydration,
      nutritional support and hemodialysis treatments with low-calcium bath led to
      clinical improvement and correction of his calcium. This case illustrates the
      dangers of pica in dialysis patients and describes modalities of treatment and
      detection of this high risk behavior. 

PMID- 25852919
TI  - Erdheim-Chester disease and knee pain in a dialysis patient.
AB  - Erdheim-Chester disease is a rare inflammatory condition characterized by a non
      Langerhans histiocytic infiltration, involving the skeleton, nervous system,
      viscera, retroperitoneum and elsewhere. The aetiology is unknown. Positron
      emission tomography shows areas of involvement. We managed a dialysis patient
      with knee pain; a bone marrow specimen showed typical CD68 positive, but CD1a
      negative cells. We initiated interferon-alpha therapy although other options
      remain open. In our patient, the simultaneous presence of secondary
      hyperparathyroidism with tumorous calcifications provided an interesting
      additional differential diagnostic possibility regarding skeletal pain. 

PMID- 25852920
TI  - Exudative detachment as a masquerader in hypoalbuminaemic patients.

PMID- 25852921
TI  - Asymptomatic proteinuria, renal cysts and dorsal pancreas agenesis.

PMID- 25852922
TI  - Polycystic horseshoe kidney: dealing with double trouble.

PMID- 25852923
TI  - Mucormycosis with diabetic and lupus nephropathy.

PMID- 25852924
TI  - Generalized aneurysmal disease in association with autosomal dominant polycystic
      disease.

PMID- 25852925
TI  - Uremic frost.

PMID- 25852926
TI  - Tubulointerstitial nephritis and uveitis syndrome in an elderly woman.

PMID- 25852927
TI  - Spontaneous tumor lysis syndrome in a case of B-cell non-Hodgkin's lymphoma.

PMID- 25852928
TI  - Nephrotic syndrome in acute promyelocytic leukemia.

PMID- 25852929
TI  - Early Enterococcus-associated acute postinfectious glomerulonephritis after
      kidney transplant.

PMID- 25852930
TI  - Combined pulmonary venous thromboembolism and renal artery thrombosis in a
      patient with non-small cell lung cancer.

PMID- 25852931
TI  - Membrane and centrifugal therapeutic plasma exchange: practical difficulties in
      anticoagulating the extracorporeal circuit.

PMID- 25852932
TI  - Treatment of acute non-anion gap metabolic acidosis.
AB  - Acute non-anion gap metabolic acidosis, also termed hyperchloremic acidosis, is
      frequently detected in seriously ill patients. The most common mechanisms leading
      to this acid-base disorder include loss of large quantities of base secondary to
      diarrhea and administration of large quantities of chloride-containing solutions
      in the treatment of hypovolemia and various shock states. The resultant acidic
      milieu can cause cellular dysfunction and contribute to poor clinical outcomes.
      The associated change in the chloride concentration in the distal tubule lumen
      might also play a role in reducing the glomerular filtration rate. Administration
      of base is often recommended for the treatment of acute non-anion gap acidosis.
      Importantly, the blood pH and/or serum bicarbonate concentration to guide the
      initiation of treatment has not been established for this type of metabolic
      acidosis; and most clinicians use guidelines derived from studies of high anion
      gap metabolic acidosis. Therapeutic complications resulting from base
      administration such as volume overload, exacerbation of hypertension and
      reduction in ionized calcium are likely to be as common as with high anion gap
      metabolic acidosis. On the other hand, exacerbation of intracellular acidosis due
      to the excessive generation of carbon dioxide might be less frequent than in high
      anion gap metabolic acidosis because of better tissue perfusion and the ability
      to eliminate carbon dioxide. Further basic and clinical research is needed to
      facilitate development of evidence-based guidelines for therapy of this important
      and increasingly common acid-base disorder. 

PMID- 25852933
TI  - Parathyroid gland autotransplantation after total thyroidectomy in surgical
      management of hypopharyngeal and laryngeal carcinomas: A case series.
AB  - BACKGROUND AND OBJECTIVES: Total thyroidectomy is indicated in most cases with
      postcricoid carcinoma, circumferential hypopharyngeal carcinoma and in advanced
      laryngeal carcinoma. Persistent hypoparathyroidism is a frequent complication
      after total thyroidectomy which is difficult to manage unlike hypothyroidism.
      This study was to assess the feasibility of parathyroid gland autotranplantation
      after total thyroidectomy in advanced carcinomas and their effectiveness in
      preventing persistent hypoparathyroidism. METHODS: This study included 26
      patients with hypopharyngeal and laryngeal carcinoma presented to National Cancer
      Institute, Cairo University. Total thyroidectomy and total parathyroid gland
      excision were performed as a part of adequate oncologic surgical procedure. The
      parathyroid glands were identified, resected and stored in iced saline.
      Histological confirmation was necessary before implantation into separated muscle
      pockets in the anterior forearm muscles. Regular samples were drawn to assess
      serum parathormone and calcium levels. RESULTS: All patients experienced
      hypocalcaemia within 1-5 days after operation. Only one patient experienced
      parathyroid graft failure while the remaining patients were normocalcemic during
      follow up after surgery, indicating functioning parathyroid grafts. CONCLUSIONS:
      Parathyroid gland autotranplantation is a simple safe technique with high success
      rate in preventing persistent hypoparathyroidism after total thyroidectomy in
      surgical management of advanced hypopharyngeal and laryngeal carcinomas.

PMID- 25852934
TI  - Recurrent lung atelectasis from fibrin plugs as a very early complication of
      bronchial thermoplasty: a case report.
AB  - BACKGROUND: Bronchial thermoplasty (BT) is a new therapeutic option for severe
      refractory asthma not controlled despite high dose inhaled corticosteroids plus
      long-acting bronchodilators and omalizumab in selected cases. Risk of pulmonary
      atelectasis after BT in severe asthma has been described in literature, but no
      details have been reported on the possible mechanisms of the complication. CASE
      PRESENTATION: A 49-year-old male with severe uncontrolled asthma was referred to
      BT. One hour after the first procedure, acute respiratory failure occurred with
      PaO2/FiO2 < 300. A CT scan showed atelectasis of the right lower and middle
      lobes. A new bronchoscopy was performed under non-invasive ventilation; the right
      lower and middle lobe bronchus were occluded by bronchus-shaped plugs, that were
      very difficult to remove despite repeated saline washings and fragmentation with
      forceps. The patient had a rapid resolution of respiratory failure. Four weeks
      later, 6 hours after the second session of BT, severe bronchospasm occurred with
      respiratory failure. Chest X-Ray showed atelectasis of the left lower lobe,
      prompting to perform a new flexible bronchoscopy on non-invasive ventilation. The
      exam showed again a plug occluding the left lower lobar bronchus, removed with
      forceps and washings. The histological analysis of the plugs demonstrated the
      massive presence of fibrin with mucus debris, rare Charcot-Leyden crystals,
      scattered macrophages, neutrophils, eosinophils and bronchial epithelial cells.
      CONCLUSION: The originality of our case report is related to the recurrence of
      bronchial plugging with lobar atelectasis within one and five hours respectively,
      after two sequential BT procedures. At the histological evaluation the bronchial
      plugs appeared very different from the typical mucoid asthma plugs, being
      composed prevalently by fibrin. It can be hypothesized that intense thermal
      stimulation of the bronchial mucosa may represent a strong boost for inflammation
      in susceptible patients, with microvascular alteration induced directly by heat
      or through the release of mediators. Although in severe asthma a risk of
      atelectasis from the classical asthma mucoid plugs may be expected, the
      peculiarity of our case resides in the formation of fibrin plugs whose direct
      correlation with BT should be considered.

PMID- 25852935
TI  - Co morbidities of Myofascial Neck Pain among Information Technology
      Professionals.
AB  - OBJECTIVES: The objective of this study was to identify the musculoskeletal co
      morbidities of neck pain of myofascial origin among IT professionals. METHODS: A
      retrospective report analysis of 5357 IT professionals from various IT companies
      in India was conducted. Demographic details, type and intensity of the
      musculoskeletal problems, employee feedbacks on status of musculoskeletal health
      and physician's diagnosis were analysed. Descriptive statistics were used to
      describe the age, gender, body area affected and nature of work. Chi square test
      was used to find the association between musculoskeletal co-morbidities and
      myofascial neck pain (MNP). RESULTS: The study participants were predominantly
      males (71%). 41% of the population used laptops, 35% desktops and 24% both. Neck
      pain was the commonest reported symptom, followed by low back, shoulder and arm
      pain respectively. Statistical analysis also revealed that low back pain and
      shoulder pain, had a significant association with neck pain. Further analysis
      revealed that there was a significant association between the presence of MNP and
      thoracic outlet syndrome (p < 0.001) and fibromyalgia syndrome (p < 0.001). Other
      than the listed co-morbidities, eye strain was also found to be associated with
      MNP. CONCLUSIONS: Low back pain and shoulder pain was found to be co morbid
      symptoms noted among IT professionals with MNP. Thoracic outlet syndrome and
      fibromyalgia were found to be the most commonly associated disorders with MNP
      among IT professionals.

PMID- 25852936
TI  - Musculoskeletal disorders of the upper extremities due to extensive usage of hand
      held devices.
AB  - OBJECTIVE: The use of hand held devices (HHD) such as mobile phones, game
      controls, tablets, portable media players and personal digital assistants have
      increased dramatically in past decade. While sending a text message or using the
      controls of the HHD the users need to use their thumb and other palm muscles
      extensively. The objective of this study was to describe the risk factors and
      clinical features of the musculoskeletal disorders (MSDs) arising due to usage of
      hand held devices and to evaluate the effectiveness of a sequenced rehabilitation
      protocol. METHODS: A retrospective report analysis of 70 subjects, who were
      diagnosed to have a MSD affecting the upper extremities, was conducted. Medical
      charts from a tertiary level rehabilitation centre from 2005-2013 were analysed.
      All the subjects reported pain in their upper extremities following extensive
      usage of HHD and were examined and diagnosed to have a MSD by an orthopaedic and
      rehabilitation physician. After the assessment and diagnosis, all the patients
      underwent rehabilitation using a sequenced protocol. RESULTS: All the subjects
      reported pain in the thumb and forearm with associated burning, numbness and
      tingling around the thenar aspect of the hand, and stiffness of wrist and hand.
      43 subjects had symptoms on the right side; 9 on left and 18 had bilateral
      symptoms. Correlation was found between hand dominance and MSD. 33 subjects
      complained of onset of symptoms following extensive text messaging. All the
      subjects were diagnosed to have tendinosis of Extensor Pollicis Longus and
      Myofascial Pain Syndrome affecting the 1st interossei, thenar group of muscles
      and Extensor Digitorum Communis. 23 of the subjects were senior executives, among
      these 7 were CEO's of major multinational companies in India. All the subjects
      recovered completely following the rehabilitation. CONCLUSIONS: The study
      concluded that mobile phones and gadgets that promoted the predominant usage of
      thumb or only one finger while texting or using the controls were associated with
      a higher prevalence of MSDs. Treatment using a sequenced rehabilitation protocol
      was found to be effective.

PMID- 25852937
TI  - Relationship between Psychosocial Risk Factors and Work-Related Musculoskeletal
      Disorders among Public Hospital Nurses in Malaysia.
AB  - OBJECTIVE: This study examined the relationships between psychosocial work
      factors and risk of WRMSDs among public hospital nurses in the Klang Valley,
      Malaysia. METHODS: We conducted a cross-sectional study among 660 public hospital
      nurses. A self-administered questionnaire was used to collect data on the
      occurrence of WRMSDs according to body regions, socio-demographic profiles,
      occupational information and psychosocial risk factors. 468 questionnaires were
      returned (response rate of 71%), and 376 questionnaires qualified for subsequent
      analysis. Univariate analyses were applied to test for mean and categorical
      differences across the WRMSDs; multiple logistic regression was applied to
      predict WRMSDs based on the Job Strain Model's psychosocial risk factors.
      RESULTS: Over two thirds of the sample of nurses experienced discomfort or pain
      in at least one site of the musculoskeletal system within the last year. The neck
      was the most prevalent site (48.94%), followed by the feet (47.20%), the upper
      back (40.69%) and the lower back (35.28%). More than 50% of the nurses complained
      of having discomfort in region one (neck, shoulders and upperback) and region
      four (hips, knees, ankles, and feet). The results also revealed that
      psychological job demands, job strain and iso-strain ratio demonstrated
      statistically significant mean differences (p < 0.05) between nurses with and
      without WRMSDs. According to univariate logistic regression, all psychosocial
      risk factors illustrated significant association with the occurrence of WRMSDs in
      various regions of the body (OR: 1.52-2.14). Multiple logistic regression showed
      all psychosocial risk factors were significantly associated with WRMSDs across
      body regions (OR: 1.03-1.19) except for region 1 (neck, shoulders and upper back)
      and region 4 (hips, knees, ankles, and feet). All demographic variables except
      for years of employment were statistically and significantly associated with
      WRMSDs (p < 0.05). CONCLUSIONS: The findings indicated the high prevalence of
      WRMSDs in many body regions, and the risks of developing WRMSDs according to the
      various body regions were associated with important psychosocial risk factors
      based on the job strain model. These findings have implications for the
      management of WRMSDs among public hospital nurses in the Klang Valley, Malaysia.

PMID- 25852938
TI  - Effect of Long Working Hours on Self-reported Hypertension among Middle-aged and
      Older Wage Workers.
AB  - OBJECTIVES: Many studies have reported an association between overwork and
      hypertension. However, research on the health effects of long working hours has
      yielded inconclusive results. The objective of this study was to identify an
      association between overtime work and hypertension in wage workers 45 years and
      over of age using prospective data. METHODS: Wage workers in Korea aged 45 years
      and over were selected for inclusion in this study from among 10,254 subjects
      from the Korean Longitudinal Study of Ageing. Workers with baseline hypertension
      and those with other major diseases were excluded. In the end, a total of 1,079
      subjects were included. A Cox proportional hazards model was used to calculate
      hazard ratios and adjust for baseline characteristics such as sex, age,
      education, income, occupation, form of employment, body mass index, alcohol
      habit, smoking habit, regular exercise, and number of working days per week.
      Additional models were used to calculate hazard ratios after gender
      stratification. RESULTS: Among the 1,079 subjects, 85 workers were diagnosed with
      hypertension during 3974.2 person-months. The average number of working hours per
      week for all subjects was 47.68. The proportion of overtime workers was 61.0%
      (cutoff, 40 h per week). Compared with those working 40 h and less per week, the
      hazard ratio of subjects in the final model, which adjusted for all selected
      variables, working 41-50 h per week was 2.20 (95% confidence interval [CI], 1.19
      4.06), that of subjects working 51-60 h per week was 2.40 (95% CI, 1.07-5.39),
      and that of subjects working 61 h and over per week was 2.87 (95% CI, 1.33-6.20).
      In gender stratification models, the hazard ratio of the females tended to be
      higher than that of the males. CONCLUSION: As the number of working hours per
      week increased, the hazard ratio for diagnosis of hypertension significantly
      increased. This result suggests a positive association between overtime work and
      the risk of hypertension.

PMID- 25852939
TI  - Vitamin D status and associated occupational factors in Korean wage workers: data
      from the 5th Korea national health and nutrition examination survey (KNHANES 2010
      2012).
AB  - OBJECTIVES: Vitamin D deficiency is increasing worldwide. However, few studies
      have attempted to examine the vitamin D status of wage workers and the
      correlation between vitamin D deficiency and working conditions. Hence, we aimed
      to evaluate the prevalence of vitamin D deficiency and the association between
      occupational conditions and vitamin D deficiency among Korean wage workers.
      METHODS: Wage workers aged 20-65 years from the 5th Korea National Health and
      Nutrition Examination Survey (KNHANES 2010-2012; n = 5409) were included in our
      analysis. We measured the prevalence of vitamin D deficiency and identified the
      correlations with the working conditions of these subjects. RESULTS: The
      prevalence of vitamin D deficiency in male and female subjects was 69.5% and
      83.1%, respectively. Among the male subjects, a significant correlation between
      vitamin D deficiency and working conditions was observed among shift workers,
      office workers, and permanent workers. No significant correlation with any type
      of working conditions was observed among female subjects. CONCLUSION: The
      prevalence of vitamin D deficiency among Korean wage workers was very high and
      was found to correlate significantly with working conditions, likely because of
      insufficient exposure to sunlight associated with certain types of work. Wage
      workers require more frequent outdoor activity and nutrition management to
      maintain sufficient vitamin D level.

PMID- 25852940
TI  - Acute health effects of accidental chlorine gas exposure.
AB  - OBJECTIVES: This study was conducted to report the course of an accidental
      release of chlorine gas that occurred in a factory in Gumi-si, South Korea, on
      March 5, 2013. We describe the analysis results of 2 patients hospitalized
      because of chlorine-induced acute health problems, as well as the clinical
      features of 209 non-hospitalized patients. METHODS: We analyzed the medical
      records of the 2 hospitalized patients admitted to the hospital, as well as the
      medical records and self-report questionnaires of 209 non-hospitalized patients
      completed during outpatient treatment. RESULTS: Immediately after the exposure,
      the 2 hospitalized patients developed acute asthma-like symptoms such as cough
      and dyspnea, and showed restrictive and combined pattern ventilatory defects on
      the pulmonary function test. The case 1 showed asthma-like symptoms over six
      months and diurnal variability in peak expiratory flow rate was 56.7%. In case 2,
      his FEV1 after treatment (93%) increased by 25% compared to initial FEV1 (68%).
      Both cases were diagnosed as chlorine-induced reactive airways dysfunction
      syndrome (RADS) on the basis of these clinical features. The most frequent chief
      complaints of the 209 non-hospitalized patients were headache (22.7%), followed
      by eye irritation (18.2%), nausea (11.2%), and sore throat (10.8%), with
      asymptomatic patients accounting for 36.5%. The multiple-response analysis of
      individual symptom revealed headache (42.4%) to be the most frequent symptom,
      followed by eye irritation (30.5%), sore throat (30.0%), cough (29.6%), nausea
      (27.6%), and dizziness (27.3%). CONCLUSIONS: The 2 patients hospitalized after
      exposure to chlorine gas at the leakage site showed a clinical course
      corresponding to RADS. All of the 209 non-hospitalized patients only complained
      of symptoms of the upper airways and mucous membrane irritation.

PMID- 25852941
TI  - The association between concealing emotions at work and medical utilization in
      Korea.
AB  - OBJECTIVES: We aimed to investigate the association between concealing emotions
      at work and medical utilization. METHODS: Data from the 2007-2009 4th Korea
      National Health and Nutrition Examination Survey (KNHANES IV) was used, 7,094
      participants (3,837 males, 3,257 females) aged between 20 and 54 who were
      economically active and completed all necessary questionnaire items were
      included. Odds ratios (ORs) and 95% confidence intervals (95% CI) for differences
      in hospitalization, outpatient visits, and pharmaceutical drug use between those
      who concealed their emotions and those who did not were investigated using
      logistic regression models with and without gender stratification. RESULTS: Among
      those who concealed their emotions (n = 2,763), 47.4% were females, and 50.1% had
      chronic disease. In addition, 9.7% of the concealing emotions group had been
      hospitalized within the last year, 24.8% had been outpatients in the last two
      weeks, and 28.3% had used pharmaceutical drugs in the last two weeks. All ORs
      represent the odds of belonging to the concealing emotions group over the non
      concealing emotions group. After adjustment for individual, occupational,
      socioeconomic and disease factors, the adjusted ORs (95% CI) in hospitalization
      are 1.29 (1.08 ~ 1.53) in the total population, 1.25 (0.98 ~ 1.60) in males and
      1.30 (1.02 ~ 1.66) in females, in outpatient visits are 1.15 (1.02 ~ 1.29) in the
      total population, 1.05 (0.88 ~ 1.24) in males and 1.25 (1.06 ~ 1.47) in females
      and in pharmaceutical drug use are 1.12 (1.01 ~ 1.25) in the total population,
      1.08 (0.92 ~ 1.27) in males and 1.14 (0.98 ~ 1.33) in females. CONCLUSIONS: Those
      who concealed their emotions at work were more likely to use medical services.
      Moreover, the health effects of concealing emotions at work might be more
      detrimental in women than in men.

PMID- 25852942
TI  - Presenteeism among self-employed workers: Korean working conditions survey.
AB  - OBJECTIVE: Presenteeism has become a public concern recently. Thus, we aimed to
      understand the relationship between self-employed workers and presenteeism using
      a nationally representative sample of Korean workers. METHODS: Using data from
      the Korean Working Conditions Survey conducted in 2011, a total of 43,392 workers
      including paid employees and self-employed workers were analyzed. The effect of
      employment status on presenteeism was analyzed using logistic regression
      analysis. The independent variables were socioeconomic characteristics, working
      conditions, and working environments. RESULTS: Among the 43,392 workers, 34,783
      were paid and 8,609 were self-employed. Self-employed workers were more likely to
      exhibit presenteeism than were paid workers. An elevated odds ratio of 1.27 (95%
      CI 1.19-1.36) was found for presenteeism among self-employed workers. CONCLUSION:
      Being self-employed was significantly related with exhibiting presenteeism.
      Additional research should investigate whether other factors mediate the
      relationship between employment status and presenteeism as well as ways to reduce
      presenteeism among self-employed workers.

PMID- 25852943
TI  - Workers' experiences with compensated sick leave due to musculoskeletal disorder:
      a qualitative study.
AB  - OBJECTIVES: The most common occupational disease that is compensated by
      Industrial Accident Compensation Insurance (IACI) in Korea is musculoskeletal
      disease (MSD). Although complaints about the workers' compensation system have
      been raised by injured workers with MSD, studies that examine workers'
      experiences with the Korean system are rare. This paper is a qualitative study
      designed to examine injured workers' experiences with the workers' compensation
      system in Korea. The aim of this study is to explore the drawbacks of the
      workers' compensation system and to suggest ways to improve this system. METHODS:
      All workers from an automobile parts factory in Anseong, GyeongGi province who
      were compensated for MSD by IACI from January 2003 to August 2013 were invited to
      participate. Among these 153 workers, 142 workers completed the study. Semi
      structured open-ended interviews and questionnaires were administered by
      occupational physicians. The responses of 131 workers were analyzed after
      excluding 11 workers, 7 of whom provided incomplete answers and 4 of whom were
      compensated by accidental injury. Based on their age, disease, department of
      employment, and compensation time, 16 of these 131 workers were invited to
      participate in an individual in-depth interview. In-depth interviews were
      conducted by one of 3 occupational physicians until the interview contents were
      saturated. RESULTS: Injured workers with MSD reported that the workers'
      compensation system was intimidating. These workers suffered more emotional
      distress than physical illness due to the workers' compensation system. Injured
      workers reported that they were treated inadequately and remained isolated for
      most of the recuperation period. The compensation period was terminated without
      ample guidance or a plan for an appropriate rehabilitation process. CONCLUSIONS:
      Interventions to alleviate the negative experiences of injured workers, including
      quality control of the medical care institutions and provisions for mental and
      psychological care for injured workers, are needed to help injured workers return
      to work earlier and more healthy.

PMID- 25852944
TI  - The relationship between working condition factors and well-being.
AB  - OBJECTIVES: Working conditions can exert influence on the physical, mental, and
      even social health of workers. Well-being is an appropriate index for the
      evaluation of a person's overall health. This paper investigated the association
      between various working conditions and worker's well-being. METHODS: Data from
      10,019 interviews were collected from the second wave of the Korean Working
      Conditions Survey (2010) conducted by the Korea Occupational Safety and Health
      Agency between June and October 2010. The data from 5,995 employed workers were
      examined in this study. Well-being was measured through the WHO Five Well-Being
      Index (1998 version). Sociodemographic and working conditions were analyzed.
      Adjusted odds ratios for well-being were calculated with adjusted
      sociodemographic factors, working condition factors, or both. RESULTS: Workers'
      well-being was significantly higher when they were satisfied with their working
      conditions (OR = 1.656, 95% CI = 1.454-1.885), when their actual working hours
      were the same as their anticipated working hours (OR = 1.366, 95% CI: 1.120
      1.666) or exceeding less than 10 hours (OR = 1.245, 95% CI: 1.004-1.543), and
      when their employment was stable (OR = 1.269, 95% CI: 1.098-1.467). CONCLUSIONS:
      This study supports the association between working condition factors and well
      being in workers.

PMID- 25852945
TI  - Predicting risk of COPD in primary care: development and validation of a clinical
      risk score.
AB  - OBJECTIVES: To develop and validate a clinical risk score to identify patients at
      risk of chronic obstructive pulmonary disease (COPD) using clinical factors
      routinely recorded in primary care. DESIGN: Case-control study of patients
      containing one incident COPD case to two controls matched on age, sex and general
      practice. Candidate risk factors were included in a conditional logistic
      regression model to produce a clinical score. Accuracy of the score was estimated
      on a separate external validation sample derived from 20 purposively selected
      practices. SETTING: UK general practices enrolled in the Clinical Practice
      Research Datalink (1 January 2000 to 31 March 2006). PARTICIPANTS: Development
      sample included 340 practices containing 15 159 newly diagnosed COPD cases and 28
      296 controls (mean age 70 years, 52% male). Validation sample included 2259 cases
      and 4196 controls (mean age 70 years, 50% male). MAIN OUTCOME MEASURES: Area
      under the receiver operator characteristic curve (c statistic), sensitivity and
      specificity in the validation practices. RESULTS: The model included four
      variables including smoking status, history of asthma, and lower respiratory
      tract infections and prescription of salbutamol in the previous 3 years. It had a
      high average c statistic of 0.85 (95% CI 0.83 to 0.86) and yielded a sensitivity
      of 63.2% (95% CI 63.1 to 63.3) and specificity 87.4% (95% CI 87.3 to 87.5).
      CONCLUSIONS: Risk factors associated with COPD and routinely recorded in primary
      care have been used to develop and externally validate a new COPD risk score.
      This could be used to target patients for case finding.

PMID- 25852946
TI  - The effect of macrobiotic Ma-Pi 2 diet on systemic inflammation in patients with
      type 2 diabetes: a post hoc analysis of the MADIAB trial.
AB  - INTRODUCTION: Current guidelines for the management of type 2 diabetes (T2D)
      emphasize diet as essential therapy. However, the effect of diet on systemic
      inflammation remains unclear. We investigated the effects of consuming a
      macrobiotic Ma-Pi 2 diet versus a standard recommended diet (control diet) on
      markers of inflammation in patients with T2D. METHODS: This was a post hoc
      analysis of the MADIAB trial, a 21-day randomized controlled trial conducted in
      51 patients (25 males and 26 females) with T2D. Patients were randomized 1:1 to
      the Ma-Pi 2 macrobiotic diet or a control diet based on dietary guidelines for
      T2D. Biological antioxidant potential of plasma and circulating levels of high
      sensitivity C reactive protein, interleukin-6, tumor necrosis factor-alpha, and
      insulin-like growth factor-1 were assessed. RESULTS: After 21 days on the Ma-Pi 2
      or control diet, markers of inflammation were reduced in both groups. The
      antioxidant potential of plasma improved significantly in the Ma-Pi group. A
      significant reduction in insulin growth factor-1 was observed in the Ma-Pi group
      versus control group (p<0.001). CONCLUSIONS: Findings of this post hoc analysis
      demonstrated that the Ma-Pi 2 diet is a safe dietary strategy to reduce levels of
      the markers of insulin resistance and inflammation, compared with baseline
      values, in the short term. Furthermore, the Ma-Pi 2 diet was superior to the
      control diet in reducing insulin growth factor-1 and may be beneficial for
      patients with T2D. TRIAL REGISTRATION NUMBER: Current Controlled Trials
      ISRCTN10467793.

PMID- 25852947
TI  - The role of cardiac biomarkers for predicting left ventricular dysfunction and
      cardiovascular mortality in acute exacerbations of COPD.
AB  - The presence of cardiovascular comorbidities is frequently associated with poor
      outcomes in chronic obstructive pulmonary disease (COPD). No clear role has been
      defined for cardiac biomarkers in acute exacerbations of COPD (AECOPD). The aim
      of this systematic review was to examine the prognostic value of brain
      natriuretic peptide (BNP) and troponins in patients with AECOPD. Two independent
      authors searched the PubMed and Cochrane Library to collect clinical trials,
      observational studies and meta-analyses studying the prognostic value of cardiac
      biomarkers in AECOPD. The reference lists of all the included studies were also
      reviewed. A total of 14 studies were included in the review, of which 10 measured
      troponins, 7 measured BNP or NT-proBNP, and 3 measured both. Of the studies that
      used mortality in AECOPD as an end point, some but not all found that elevated
      BNP and/or troponins were associated with increased mortality. Of the studies
      that used left ventricular (LV) dysfunction in AECOPD as an end point, all found
      a significant association between elevated BNP and troponins in the diagnosis of
      LV dysfunction. In summary, it appears that there may be a link between an
      elevated level of BNP or NT-proBNP and increased cardiovascular mortality in
      AECOPD, although the data currently available are not conclusive. The
      inconsistencies in biomarkers measured, time points of measurements and the
      variability in outcome measured preclude more robust analysis. 

PMID- 25852948
TI  - The no-touch vein graft for coronary artery bypass surgery preserves the left
      ventricular ejection fraction at 16 years postoperatively: long-term data from a
      longitudinal randomised trial.
AB  - OBJECTIVES: To assess the left ventricular heart function and the clinical
      outcome 16 years after coronary artery bypass surgery. DESIGN: In a randomised
      trial, the no-touch (NT) vein graft in coronary artery bypass surgery has shown a
      superior patency rate, a slower progression of atherosclerosis and better
      clinical outcome compared to the conventional (C) vein graft at 8.5 years. All
      patients at mean time 16 years were offered an echocardiographic and clinical
      examination. RESULTS: In the NT-group 34 patients and in the C-group 31 patients
      underwent an echocardiography examination. A significantly better left ventricle
      ejection fraction was seen in the NT-group compared to the C-group (57.9% vs
      49.4%; p=0.011). The size of the left atrium in NT was 21.7 cm(2) compared to
      23.9 cm(2) in C; p=0.034. No patient in NT had atrial fibrillation compared to
      five patients in C (p=0.021). Patients with a brain natriuretic peptide value
      (BNP) >=150 was 30% in NT compared to 38% in C. Total mortality was 25% in NT vs
      27% in C. Cardiac-related deaths were 8% and 12% in NT and C respectively.
      CONCLUSIONS: The NT vein graft preserves the left ventricular ejection fraction
      after 16 years. A smaller left atrium, a lower BNP and no atrial fibrillation
      indicates an improved diastolic left ventricular function in the NT-group. TRIAL
      REGISTRATION: The study is registered with clinicaltrials.gov (NCT01686100) and
      The Research and Development registry in Sweden (no. 102841).

PMID- 25852949
TI  - Impact of proctoring on success rates for percutaneous revascularisation of
      coronary chronic total occlusions.
AB  - OBJECTIVE: To assess the impact of proctoring for chronic total occlusion (CTO)
      percutaneous coronary intervention (PCI) in six UK centres. METHODS: We
      retrospectively analysed 587 CTO procedures from six UK centres and compared
      success rates of operators who had received proctorship with success rates of the
      same operators before proctorship (pre-proctored) and operators in the same
      institutions who had not been proctored (non-proctored). There were 232 patients
      in the pre-proctored/non-proctored group and 355 patients in the post-proctored
      group. Complexity was assessed by calculating the Japanese CTO (JCTO) score for
      each case. RESULTS: CTO PCI success was greater in the post-proctored compared
      with the pre-proctored/non-proctored group (77.5% vs 62.1%, p<0.0001). In more
      complex cases where JCTO>=2, the difference in success was greater (70.7% vs
      49.5%, p=0.0003). After proctoring, there was an increase in CTO PCI activity in
      centres from 2.5% to 3.5%, p<0.0001 (as a proportion of total PCI), and the
      proportion of very difficult cases with JCTO score >=3 increased from 15.3%
      (35/229) to 29.7% (105/354), p<0.0001. CONCLUSIONS: Proctoring resulted in an
      increase in procedural success for CTO PCI, an increase in complex CTO PCI and an
      increase in total CTO PCI activity. Proctoring may be a valuable way to improve
      access to CTO PCI and the likelihood of procedural success.

PMID- 25852950
TI  - Breathing difficulty in a middle-aged woman - a dangerous cause?
AB  - Temporal lobe epilepsy is a rare but treatable cause of apnoea. 

PMID- 25852951
TI  - The US hospital standardised mortality ratio: Retrospective database study of
      Massachusetts hospitals.
AB  - OBJECTIVES: To present a case-mix adjustment model that can be used to calculate
      Massachusetts hospital standardised mortality ratios and can be further adapted
      for other state-wide data-sets. DESIGN: We used binary logistic regression models
      to predict the probability of death and to calculate the hospital standardised
      mortality ratios. Independent variables were patient sociodemographic
      characteristics (such as age, gender) and healthcare details (such as admission
      source). Statistical performance was evaluated using c statistics, Brier score
      and the Hosmer-Lemeshow test. SETTING: Massachusetts hospitals providing care to
      patients over financial years 2005/6 to 2007/8. PATIENTS: 1,073,122 patients
      admitted to Massachusetts hospitals corresponding to 36 hospital standardised
      mortality ratio diagnosis groups that account for 80% of in-hospital deaths
      nationally. MAIN OUTCOME MEASURES: Adjusted in-hospital mortality rates and
      hospital standardised mortality ratios. RESULTS: The significant factors
      determining in-hospital mortality included age, admission type, primary
      diagnosis, the Charlson index and do-not-resuscitate status. The Massachusetts
      hospital standardised mortality ratios for acute (non-specialist) hospitals
      ranged from 60.3 (95% confidence limits 52.7-68.6) to 130.3 (116.1-145.8). The
      reference standard hospital standardised mortality ratio is 100 with the values
      below and above 100 suggesting either random or special cause variation. The
      model was characterised by excellent discrimination (c statistic 0.87), high
      accuracy (Brier statistics 0.03) and close agreement between predicted and
      observed mortality rates. CONCLUSIONS: We have developed a case-mix model to give
      insight into mortality rates for patients served by hospitals in Massachusetts.
      Our analysis indicates that this technique would be applicable and relevant to
      Massachusetts hospital care as well as to other US hospitals.

PMID- 25852952
TI  - Trends in hospital admissions for Varicella and Zoster viruses in England,
      2001/2002-2010/2011: time trend study.
AB  - OBJECTIVES: Varicella and Herpes Zoster are common infectious diseases. Various
      studies have estimated rates of infection for both manifestations of these
      infections; however rates of hospital admissions across the country have not
      previously been described. This paper presents data on hospital admissions in
      England for Varicella and Herpes Zoster from 2001/2002 to 2010/2011. DESIGN: Time
      trends study of all hospital admissions for Varicella and Herpes Zoster from
      2001/2002 to 2010/2011 in England. SETTING: Hospital admissions across England
      from 2001/2002 to 2010/2011. PARTICIPANTS: We included all patients admitted to
      hospital from 2001/2002 to 2010/2011 diagnosed with Varicella and Zoster
      according to the International Classification of Diseases version 10 (ICD-10).
      MAIN OUTCOME MEASURES: The main outcome measures were admission rates by year and
      diagnosis and age-specific admission rates for Varicella and Zoster from
      2001/2002 to 2010/2011. METHODS: We analysed data from Hospital Episode
      Statistics which include patient characteristics such as age which was used here
      in order to standardise rates to the relevant population. We also used mid-year
      population estimates from the Office for National Statistics for standardisation
      purposes. All analyses were conducted using Stata v12.0. RESULTS: The hospital
      admission rate for Varicella cases has risen by 1.8% over the 10-year study
      period. While the overall admission rates for Herpes Zoster have decreased by 4%
      from 2001/2002 levels. The vast majority of Varicella and Zoster admissions were
      not associated with any complications. CONCLUSION: The introduction of Herpes
      Zoster vaccine is anticipated to decrease hospital admissions in older age groups
      further. A repeat of this study after a further period of time would help to
      evaluate the impact of the introduction of Herpes Zoster vaccine in England on
      hospital admissions.

PMID- 25852953
TI  - The Risotto sign - a severe inflammatory bursitis with rice body formation,
      complicating a rotator cuff repair with a bioabsorbable suture anchor.
AB  - There is an association between inflammatory bursitis with rice body formation
      and use of bioabsorbable suture anchors. 

PMID- 25852954
TI  - Raised intracranial pressure following abdominal closure in a polytrauma patient.
AB  - We report a polytrauma case requiring simultaneous neurosurgery and laparotomy.
      Upon abdominal closure, raised intracranial pressure occurred. This illustrates
      the important physiological interplay between body compartments in critical care
      patients. 

PMID- 25852955
TI  - The bunkie test: descriptive data for a novel test of core muscular endurance.
AB  - The Bunkie test, a functional performance test consisting of 5 test positions
      (performed bilaterally), has been used to assess aspects of muscular function.
      Current performance measures are based on clinical recommendations. The purpose
      of this study was to report normative data for a healthy population. One hundred
      and twelve subjects (mean age 25.9 +/- 4.5 years) were recruited from a
      university setting. Subjects completed a demographic questionnaire prior to
      testing. Hold times for each position was measured in seconds. Subjects were able
      to hold many of the positions for a mean score of approximately 40 seconds. There
      were no side-to-side differences in test position hold times per gender. Males
      were able to hold some positions significantly longer than their female
      counterparts. Males with a lower BMI were able to hold 8 of the 10 positions
      significantly longer than those with a higher BMI. Bunkie test scores in subjects
      with a prior history of musculoskeletal injury were similar to those with no
      history of injury. The normative data presented in this study may be used by
      rehabilitation professionals when assessing and rehabilitating their patients. 

PMID- 25852956
TI  - An ovarian pregnancy in a patient with a history of bilateral salpingectomies: a
      rare case.
AB  - Background. 1 in 200 ectopic pregnancies are true ovarian pregnancies that
      fulfill the Spiegelberg criteria. Despite being rare, multiple case reports and
      series have been reported. Few cases have been published in which the event was
      preceded by salpingectomy. Case. The patient is a 32-year-old female who
      presented to the emergency room with abdominal pain. She was found to be
      pregnant, despite a history of two previous ectopic pregnancies treated with
      salpingectomies. Sonography confirmed a left adnexal mass and free fluid. Surgery
      revealed a ruptured ovarian pregnancy which was also confirmed by pathology.
      Conclusion. This is a case of an ovarian pregnancy in a patient with two previous
      salpingectomies. It underscores the importance of searching for an ectopic
      pregnancy in patients with abdominal pain after fertility impairing surgery. 

PMID- 25852957
TI  - Management of Dysphagia Pre- and Postoperatively in a Case of Eagle's Syndrome.
AB  - Eagle's syndrome (ES) is rare condition, most frequently described within the
      context of case study presentation. ES results from elongation of the styloid
      process, contributing to symptoms such as globus sensation in the throat, as well
      as pain localized to the ear, neck, face, or tongue. Additional symptoms can
      include hypersalivation, change in vocal quality, submandibular swelling, and
      dysphagia. This report discusses evaluation, diagnosis, and surgical intervention
      with respect to Eagle's Syndrome in a patient presenting with moderate-severe
      dysphagia. 

PMID- 25852958
TI  - Laparoscopic treatment of a spontaneously ruptured kidney (wunderlich syndrome).
AB  - Spontaneous, nontraumatic retroperitoneal hemorrhage or Wunderlich syndrome (WS)
      is a rare but potential life-threatening condition. In most patients a bleeding
      renal neoplasm is the cause of the retroperitoneal hematoma. The management of
      this condition includes a conservative approach in the hemodynamically stable
      patients and active treatment in the unstable patients. Active treatment includes
      angioembolization or surgery. If angioembolization is not available open surgery
      is in most cases the preferred approach. We present a patient with a
      spontaneously ruptured kidney due to a central renal angiomyolipoma, which was
      treated by laparoscopic nephrectomy. 

PMID- 25852959
TI  - p40 as a Basal Cell Marker in the Diagnosis of Prostate Glandular Proliferations:
      A Comparative Immunohistochemical Study with 34betaE12.
AB  - Immunohistochemistry is important for the accurate diagnosis of basal cells in
      atypical glandular proliferations of the prostate. p40, an isoform of p63, may be
      an adjunct to a marker panel in this setting. Biopsies of 68 patients were
      analyzed by immunohistochemistry using antibodies to 34betaE12 and p40. Basal
      cell staining was classified as negative, partial (<60%), or diffuse (>=60%);
      irregular staining was defined as discordant staining patterns. In acinar
      proliferations (N = 41), partial staining for both markers was seen in 42%, and
      diffuse staining in 46% of reactive cases. An irregular reactivity was noted in
      one case only (2%). Finally, these lesions were signed out as benign. Acinar
      proliferations negative for both markers and limited amount of glands (<=4) were
      termed atypical small acinar proliferations (ASAP). Out of six PIN lesions two
      cases showed partial, three cases showed diffuse reactivity for both markers, and
      one case was stained irregular. All cases diagnosed as prostate carcinomas (N =
      20) had no evidence of basal cell staining for neither of the markers. p40
      expression is closely correlated to 34betaE12 with respect to demonstration of
      basal cells of prostate glands and may provide further information on the dignity
      of glandular proliferations of the prostate. 

PMID- 25852960
TI  - Corrigendum to "the studies of chlorogenic Acid antitumor mechanism by gene chip
      detection: the immune pathway gene expression".
AB  - [This corrects the article DOI: 10.1155/2013/617243.]. 

PMID- 25852961
TI  - Late evaluation of upper limb arterial flow in patients after long radial
      (PiCCOTM) catheter placement.
AB  - BACKGROUND: The purpose of the study was to assess blood flow in the upper limb
      arteries after prolonged catheterization with long radial artery catheters (LRC)
      which reach the subclavian artery compared to catheterization with standard short
      radial artery catheters (SRC) and a group of upper limb flow without any catheter
      placement (NOCATH), with both SRC and NOCATH as control groups. METHODS:
      Prospective observational study with 20 patients admitted to ICU (40 upper limbs)
      with LRC and/or SRC inserted >48 h for hemodynamic monitoring. More than 45 days
      after catheter withdrawal, patients underwent a Doppler ultrasound study of both
      upper limbs. Arterial flows of arms with LRC (FlowLRC) were compared with
      arterial flows of arms with SRC (FlowSRC) and those without any catheter
      (FlowNOCATH). RESULTS: Flow in the ulnar, brachial, and subclavian arteries did
      not show any significant difference between the two types of catheters. The only
      significant difference was in the radial arteries, showing a lower mean flow in
      the arms with LRC than in the arms with SRC (2.2 vs. 8.5 cc/min; p = 0.041). Flow
      reduction in the radial artery (74%) in the arms with LRC compared to the SRC
      arms showed a tendency to increase ulnar flow as a compensatory mechanism. None
      of the patients with LRC included in our study had any ischemic events, in spite
      of observing complete flow occlusion in three radial arteries (18%) from the
      Doppler study. CONCLUSIONS: In this sample, the use of PiCCO long radial
      catheters reaching the subclavian artery did not produce chronic significant
      changes in brachial or subclavian flows. However, LRC produces a significant
      reduction in radial flow and a tendency to increase ulnar flow. When comparing
      these blood flow changes with those produced by SRC use, only the radial flow
      reduction was significantly lower, whereas the other arterial flow changes did
      not significantly differ.

PMID- 25852962
TI  - End-tidal carbon dioxide monitoring using a naso-buccal sensor is not appropriate
      to monitor capnia during non-invasive ventilation.
AB  - BACKGROUND: In acute respiratory failure, arterial blood gas analysis (ABG) is
      used to diagnose hypercapnia. Once non-invasive ventilation (NIV) is initiated,
      ABG should at least be repeated within 1 h to assess PaCO2 response to treatment
      in order to help detect NIV failure. The main aim of this study was to assess
      whether measuring end-tidal CO2 (EtCO2) with a dedicated naso-buccal sensor
      during NIV could predict PaCO2 variation and/or PaCO2 absolute values. The
      additional aim was to assess whether active or passive prolonged expiratory
      maneuvers could improve the agreement between expiratory CO2 and PaCO2. METHODS:
      This is a prospective study in adult patients suffering from acute hypercapnic
      respiratory failure (PaCO2 >= 45 mmHg) treated with NIV. EtCO2 and expiratory CO2
      values during active and passive expiratory maneuvers were measured using a
      dedicated naso-buccal sensor and compared to concomitant PaCO2 values. The
      agreement between two consecutive values of EtCO2 (delta EtCO2) and two
      consecutive values of PaCO2 (delta PaCO2) and between PaCO2 and concomitant
      expiratory CO2 values was assessed using the Bland and Altman method adjusted for
      the effects of repeated measurements. RESULTS: Fifty-four datasets from a
      population of 11 patients (8 COPD and 3 non-COPD patients), were included in the
      analysis. PaCO2 values ranged from 39 to 80 mmHg, and EtCO2 from 12 to 68 mmHg.
      In the observed agreement between delta EtCO2 and deltaPaCO2, bias was -0.3 mmHg,
      and limits of agreement were -17.8 and 17.2 mmHg. In agreement between PaCO2 and
      EtCO2, bias was 14.7 mmHg, and limits of agreement were -6.6 and 36.1 mmHg.
      Adding active and passive expiration maneuvers did not improve PaCO2 prediction.
      CONCLUSIONS: During NIV delivered for acute hypercapnic respiratory failure,
      measuring EtCO2 using a dedicating naso-buccal sensor was inaccurate to predict
      both PaCO2 and PaCO2 variations over time. Active and passive expiration
      maneuvers did not improve PaCO2 prediction. TRIAL REGISTRATION:
      ClinicalTrials.gov: NCT01489150.

PMID- 25852964
TI  - Failed noninvasive positive-pressure ventilation is associated with an increased
      risk of intubation-related complications.
AB  - BACKGROUND: Noninvasive positive-pressure ventilation (NIPPV) use has increased
      in the treatment of patients with respiratory failure. However, despite
      decreasing the need for intubation in some patients, there are no data regarding
      the risk of intubation-related complications associated with delayed intubation
      in adult patients who fail NIPPV. The objective of this study is to evaluate the
      odds of a composite complication of intubation following failed NIPPV compared to
      patients intubated primarily in the medical intensive care unit (ICU). METHODS:
      This is a single-center retrospective cohort study of 235 patients intubated
      between 1 January 2012 and 30 June 2013 in a medical ICU of a university medical
      center. A total of 125 patients were intubated after failing NIPPV, 110 patients
      were intubated without a trial of NIPPV. Intubation-related data were collected
      prospectively through a continuous quality improvement (CQI) program and
      retrospectively extracted from the medical record on all patients intubated on
      the medical ICU. A propensity adjustment for the factors expected to affect the
      decision to initially use NIPPV was used, and the adjusted multivariate
      regression analysis was performed to evaluate the odds of a composite
      complication (desaturation, hypotension, or aspiration) with intubation following
      failed NIPPV versus primary intubation. RESULTS: A propensity-adjusted
      multivariate regression analysis revealed that the odds of a composite
      complication of intubation in patients who fail NIPPV was 2.20 (CI 1.14 to 4.25),
      when corrected for the presence of pneumonia or acute respiratory distress
      syndrome (ARDS), and adjusted for factors known to increase complications of
      intubation (total attempts and operator experience). When a composite
      complication occurred, the unadjusted odds of death in the ICU were 1.79 (95% CI
      1.03 to 3.12). CONCLUSIONS: After controlling for potential confounders, this
      propensity-adjusted analysis demonstrates an increased odds of a composite
      complication with intubation following failed NIPPV. Further, the presence of a
      composite complication during intubation is associated with an increased odds of
      death in the ICU.

PMID- 25852963
TI  - Sleeping on a problem: the impact of sleep disturbance on intensive care patients
      - a clinical review.
AB  - Sleep disturbance is commonly encountered amongst intensive care patients and has
      significant psychophysiological effects, which protract recovery and increases
      mortality. Bio-physiological monitoring of intensive care patients reveal
      alterations in sleep architecture, with reduced sleep quality and continuity. The
      etiological causes of sleep disturbance are considered to be multifactorial,
      although environmental stressors namely, noise, light and clinical care
      interactions have been frequently cited in both subjective and objective studies.
      As a result, interventions are targeted towards modifiable factors to ameliorate
      their impact. This paper reviews normal sleep physiology and the impact that
      sleep disturbance has on patient psychophysiological recovery, and the
      contribution that the clinical environment has on intensive care patients' sleep.

PMID- 25852965
TI  - Development and usability testing of a Web-based decision aid for families of
      patients receiving prolonged mechanical ventilation.
AB  - BACKGROUND: Web-based decision aids are increasingly important in medical
      research and clinical care. However, few have been studied in an intensive care
      unit setting. The objectives of this study were to develop a Web-based decision
      aid for family members of patients receiving prolonged mechanical ventilation and
      to evaluate its usability and acceptability. METHODS: Using an iterative process
      involving 48 critical illness survivors, family surrogate decision makers, and
      intensivists, we developed a Web-based decision aid addressing goals of care
      preferences for surrogate decision makers of patients with prolonged mechanical
      ventilation that could be either administered by study staff or completed
      independently by family members (Development Phase). After piloting the decision
      aid among 13 surrogate decision makers and seven intensivists, we assessed the
      decision aid's usability in the Evaluation Phase among a cohort of 30 surrogate
      decision makers using the Systems Usability Scale (SUS). Acceptability was
      assessed using measures of satisfaction and preference for electronic
      Collaborative Decision Support (eCODES) versus the original printed decision aid.
      RESULTS: The final decision aid, termed 'electronic Collaborative Decision
      Support', provides a framework for shared decision making, elicits relevant
      values and preferences, incorporates clinical data to personalize prognostic
      estimates generated from the ProVent prediction model, generates a printable
      document summarizing the user's interaction with the decision aid, and can
      digitally archive each user session. Usability was excellent (mean SUS, 80 +/-
      10) overall, but lower among those 56 years and older (73 +/- 7) versus those who
      were younger (84 +/- 9); p = 0.03. A total of 93% of users reported a preference
      for electronic versus printed versions. CONCLUSIONS: The Web-based decision aid
      for ICU surrogate decision makers can facilitate highly individualized
      information sharing with excellent usability and acceptability. Decision aids
      that employ an electronic format such as eCODES represent a strategy that could
      enhance patient-clinician collaboration and decision making quality in intensive
      care.

PMID- 25852966
TI  - Immunoglobulin Resistance in Kawasaki Disease.
AB  - Background: The aim of this study was to identify risk factors for immunoglobulin
      resistance, including clinical symptoms such as arthritis and the pH of
      intravenous immunoglobulin. Methods: The data of children with Kawasaki disease
      who had received immunoglobulin were evaluated. Data regarding the brand of
      immunoglobulin administered were abstracted from the pharmacy records. Results:
      Eighty consecutive children with Kawasaki disease were evaluated (Mdnage=28
      months, 66% male). The prevalence of immunoglobulin resistance was 30%. Arthritis
      was a presenting symptom in the acute phase of Kawasaki disease in 8% (6/80, all
      male) and was seen in significant association with immunoglobulin resistance in
      comparison to those without arthritis (16.7% vs. 0.2%, p=0.008). Next, the
      immunoglobulin brand types were divided into two groups: the relatively high pH
      group (n=16), including Carimune (pH 6.6+/-0.2), and the low pH group (n=63),
      including Gamunex (pH 4-4.5) or Privigen (pH 4.6-5). Overall, no significant
      difference in immunoglobulin responsiveness was found between the low pH and the
      high pH groups (73% vs. 56%, p=0.193), although the low pH group showed a trend
      toward a larger decrease in erythrocyte sedimentation rate (p=0.048), lower
      steroid use (p=0.054), and lower coronary involvement (p=0.08) than those in the
      high pH group. Conclusions: Children presenting with arthritis in the acute phase
      of Kawasaki disease may be at risk for immunoglobulin resistance.

PMID- 25852967
TI  - The Impact of Parent's Health Literacy on Pediatric Asthma Outcomes.
AB  - Background: Health literacy has been associated with health disparities in many
      disease outcomes, including children's asthma. Parents are responsible for most
      of children's healthcare. Therefore, parents' health literacy may impact
      children's health outcomes, including asthma control. This study sought to
      determine the association between parent health literacy and children's asthma
      control among a cohort of predominately minority urban children aged between 6
      and 12 years. Methods: This cross-sectional study assessed children with asthma
      and their parents at a single outpatient visit. English-speaking parents and
      their children, aged between 6 and 12 years with physician-diagnosed asthma, were
      eligible for this study. Healthcare providers assessed asthma control and
      severity, and parents completed demographic, health literacy, asthma control, and
      asthma knowledge measures. Children completed a pulmonary function test as part
      of the Asthma Control Questionnaire (ACQ) scoring. Results: A total of 281 parent
      child dyads provided data, with the majority of parents being mothers and African
      American, with a high school level education or less. Lower parent health
      literacy was associated with worse asthma control as rated both by the provider
      (p=0.007) and the ACQ (p=0.013), despite only moderate concordance between
      ratings (rho=0.408, p<0.0001). Lower parent health literacy also was associated
      with less asthma knowledge, which was associated with worse asthma control.
      Conclusions: Higher parent health literacy was associated with more parent asthma
      knowledge and better child asthma control. Pediatric providers should consider
      tailoring education or treatment plans or utilizing universal precautions for low
      health literacy.

PMID- 25852969
TI  - Vitamin D and Asthma: Association, Causality, or Intervention?
AB  - Many observational studies have investigated the potential association between
      vitamin D and asthma. However, it is difficult to find a temporal causal
      relationship in cross-sectional or observational studies. This review presents
      recent clinical trials and the evidence of association between vitamin D and
      asthma in different patient populations and asthma status. Well-designed clinical
      trials are warranted in order to define the optimal level of vitamin D, as well
      as dosing and duration of vitamin D supplementation, in pediatric patients.

PMID- 25852968
TI  - Median Household Income: Association with Mortality in Children on Chronic
      Ventilation at Home Secondary to Bronchopulmonary Dysplasia.
AB  - Objective: The aim of this study was to determine if living in a lower income
      neighborhood is associated with mortality of patients with bronchopulmonary
      dysplasia (BPD) on home ventilation. Methods: Patients were divided into two
      groups by their ZIP code-based annual household income (Z-AHI), their year of
      birth, and the median state household income. Survival, liberation from
      ventilation, and decannulation rates were analyzed between the groups. Results:
      Over 27 years, 94 patients met our inclusion criteria: 58 (61.7%) were in the
      group with lower Z-AHI, and 36 (38.3%) were in the group with the Z-AHI above the
      median state household. Of the patients who died, 14/15 were in the lower Z-AHI
      group (p=0.003). Survival probability at 60 months of age showed no significant
      difference between the two groups: 81% [95% CI 70.9, 91.1] for the group with the
      Z-AHI below the median state household, and 100% [95% CI 100.0, 90.3] for the
      group with higher Z-AHI (p=0.31). Conclusions: The results of this study are
      descriptive, as the cause of the association between mortality rate and living in
      an area with lower household income is not yet understood. The difference in
      mortality rates between groups above and below the median state income suggests a
      serious health disparity, which warrants further study. Additional understanding
      of this effect requires more complete and direct measurement of socioeconomic
      status and individual characteristics, and better understanding of local
      environmental conditions.

PMID- 25852970
TI  - Teenage and Young Adult Cancer-Related Fatigue Is Prevalent, Distressing, and
      Neglected: It Is Time to Intervene. A Systematic Literature Review and Narrative
      Synthesis.
AB  - PURPOSE: Cancer-related fatigue in adults has been the subject of considerable
      recent research, confirming its importance as a common and debilitating symptom,
      and establishing a number of evidence-based interventions. There has, however,
      been limited focus on the fatigue suffered by teenagers and young adults with
      cancer, a group recognized as having unique experiences and developmental needs.
      We have undertaken a systematic review of the literature to provide a
      comprehensive overview of studies evaluating fatigue in this younger patient
      group in order to guide clinical practice and future research. METHOD: We
      searched MEDLINE, EMBASE, PsycINFO, and CINAHL databases for literature
      containing data relating to any aspect of fatigue in patients aged 13-24 at
      cancer diagnosis or treatment. RESULTS: Sixty articles were identified, of which
      five described interventional clinical trials. Cancer-related fatigue was
      consistently one of the most prevalent, severe, and distressing symptoms, and it
      persisted long-term in survivors. It was associated with a number of factors,
      including poor sleep, depression, and chemotherapy. There was little evidence for
      the effectiveness of any intervention, although exercise appears to be the most
      promising. Importantly, fatigue was itself a significant barrier to physical and
      social activities. CONCLUSION: Cancer-related fatigue is a major and disabling
      problem in young cancer patients. Effective management strategies are needed to
      avoid compounding the dependence and social isolation of this vulnerable patient
      group. Future research should focus on providing evidence for the effectiveness
      of interventions, of which activity promotion and management of concurrent
      symptoms are the most promising.

PMID- 25852971
TI  - Family Functioning Mediates the Association Between Neurocognitive Functioning
      and Health-Related Quality of Life in Young Adult Survivors of Childhood Brain
      Tumors.
AB  - PURPOSE: Childhood brain tumor (BT) survivors experience significant
      neurocognitive sequelae that affect health-related quality of life (HRQOL). A
      model of neurodevelopmental late effects and family functioning in childhood
      cancer survivors suggests associations between survivor neurocognitive
      functioning, family functioning, and survivor HRQOL. This study examines the
      concurrent associations between survivor neurocognitive functioning, family
      functioning, and survivor emotional HRQOL, and the indirect effects of
      neurocognitive functioning on survivor emotional HRQOL through family
      functioning. METHODS: Participants included young adult-aged childhood BT
      survivors (18-30 years old; N=34) who were on average 16 years post-diagnosis,
      and their mothers. A brief neuropsychological battery assessed working and verbal
      memory, processing speed, and executive functioning. Survivors and mothers
      completed measures of family functioning, and mothers completed a proxy-report
      measure of survivor HRQOL. RESULTS: Spearman bivariate correlations examined the
      associations between indices of survivor neurocognitive functioning and
      concurrent family functioning and survivor emotional HRQOL. Poorer survivor
      processing speed, working memory, verbal memory, and executive function were
      significantly associated with worse survivor- and mother-reported family
      functioning (r's range: 0.36-0.58). Additionally, worse survivor processing speed
      and executive function were significantly associated with poorer survivor
      emotional HRQOL (r's range: 0.44-0.48). Bootstrapping analyses provided evidence
      for the indirect effects of neurocognitive functioning on survivor emotional
      HRQOL through family functioning. CONCLUSION: These findings suggest that family
      functioning is an important variable that might mitigate the negative influence
      of neurocognitive late effects on survivors and is a potential target in future
      interventions.

PMID- 25852973
TI  - Suicide attempts among men and women with partner violence according to
      borderline personality status.

PMID- 25852974
TI  - Multimodal approach to identifying malingered posttraumatic stress disorder: a
      review.
AB  - The primary aim of this article is to aid clinicians in differentiating true
      posttraumatic stress disorder from malingered posttraumatic stress disorder.
      Posttraumatic stress disorder and malingering are defined, and prevalence rates
      are explored. Similarities and differences in diagnostic criteria between the
      fourth and fifth editions of the Diagnostic and Statistical Manual of Mental
      Disorders are described for posttraumatic stress disorder. Possible motivations
      for malingering posttraumatic stress disorder are discussed, and common
      characteristics of malingered posttraumatic stress disorder are described. A
      multimodal approach is described for evaluating posttraumatic stress disorder,
      including interview techniques, collection of collateral data, and psychometric
      and physiologic testing, that should allow clinicians to distinguish between
      those patients who are truly suffering from posttraumatic disorder and those who
      are malingering the illness. 

PMID- 25852972
TI  - Exploring Mediators of Physical Activity in Young Adult Cancer Survivors:
      Evidence from a Randomized Trial of a Facebook-Based Physical Activity
      Intervention.
AB  - PURPOSE: This study examined the effects of a physical activity (PA) intervention
      for young adult cancer survivors on changes in self-efficacy, social support, and
      self-monitoring and determined whether changes in these social cognitive theory
      constructs mediated the relationship between the intervention and changes in PA.
      METHODS: A 12-week randomized trial compared a Facebook-based intervention
      (FITNET) aimed at increasing moderate-to-vigorous intensity PA to a Facebook
      based self-help comparison group. Young adult cancer survivors (N=86, aged 21-39)
      were randomly assigned to one of the two groups. Self-report measures of PA and
      psychosocial variables were collected at baseline and after 12 weeks. RESULTS:
      The FITNET group reported lower self-efficacy for sticking to exercise (mean
      change=-0.38; 95% CI: -0.62 to -0.12; p=0.025) and social support from friends on
      social networking websites (mean change=-0.47; 95% CI: -1.45 to 0.65; p=0.039)
      relative to the self-help comparison group over time. Changes in social support
      from friends on social networking websites partially mediated the intervention
      effects on moderate-to-vigorous PA (mean indirect effect=-22.4; 95% CI: -62.0 to 
      2.8) in the unexpected direction. Across both groups, social support from friends
      and self-monitoring were positively associated with changes in moderate-to
      vigorous PA. CONCLUSION: The proposed mediators did not explain the positive
      effects of the FITNET intervention on mild PA. The lack of significant
      improvements in psychosocial constructs among FITNET participants may partly
      explain why the intervention did not increase moderate-to-vigorous PA relative to
      the self-help comparison group. Future PA interventions with young adult cancer
      survivors should examine targeting social support from friends and self
      monitoring.

PMID- 25852975
TI  - Lurasidone: a new treatment option for bipolar depression-a review.
AB  - Depressive episodes in bipolar disorder contribute to significant morbidity and
      mortality. Until recently, only quetiapine and an olanzapine-fluoxetine
      combination were approved to treat bipolar depression. Recently, lurasidone was
      approved to treat bipolar depression either as monotherapy or adjunctively with
      lithium or valproate. Lurasidone was well- tolerated, and commonly observed
      adverse reactions (incidence >=5% and at least twice the rate for placebo) were
      akathisia, extrapyramidal symptoms, and somnolence. There were no significant
      metabolic or electrocardiogram abnormalities. It is taken with food to ensure
      maximal absorption, and dose should be adjusted in patients who receive moderate
      CYP450 inhibitors or inducers and in patients with renal disease. 

PMID- 25852976
TI  - Functional cortical and cerebellar reorganization in a case of moyamoya disease.
AB  - BACKGROUND: Functional studies have been previous reported in stroke patients,
      but no studies of functional magnetic resonance imaging have been performed in
      Moyamoya disease. OBJECTIVE: To assess the cortical and cerebellar reorganization
      in a moyamoya patient. METHODS: We reported a case of a patient suffering from
      moyamoya disease, undergoing a neuropsychological assessment, a neurocognitive
      rehabilitative treatment, an electroencephalogram evaluation, and a functional
      magnetic resonance imaging examination. RESULTS: The subject showed a cognitive
      impairment, a slow electroencephalogram activity, and the ipsi- and controlateral
      motor cortex and cerebellar functional magnetic resonance imaging activation.
      CONCLUSIONS: This is the first functional magnetic resonance imaging case study
      reported in moyamoya disease. We showed a cortical reorganization, which could
      play an important role in clinical evaluation and motor recovery. The cerebellar
      activation, showed after cognitive and motor rehabilitation, could support the
      idea that the cerebellum contains several cognitive-related subregions involved
      in different functional networks in moyamoya disease.

PMID- 25852977
TI  - Use of ketamine in acute cases of suicidality.
AB  - Ketamine is an N-methyl-D- aspartate antagonist with rapid antidepressant
      effects. Research shows that ketamine has a fast onset of reduction in depressive
      symptoms and shows sustained remission of suicidal ideation in some patients.
      This article provides a brief review of the literature on the use of ketamine for
      depression and in acute cases of suicidality. The authors conclude that, while
      further investigation is needed, ketamine may be a useful treatment option for
      acute suicidality in emergency room settings. 

PMID- 25852978
TI  - Workplace bullying: a tale of adverse consequences.
AB  - Workplace bullying is defined as the repetitive and systematic engagement of
      interpersonally abusive behaviors that negatively affect both the targeted
      individual and the work organization. According to the findings of 12 studies,
      being bullied in the workplace affects approximately 11 percent of workers.
      Victims are frequently blue-collar and unskilled workers. However, there also
      appear to be gender and milieu/management factors. Emotional/psychological
      consequences of workplace bullying may include increased mental distress, sleep
      disturbances, fatigue in women and lack of vigor in men, depression and anxiety,
      adjustment disorders, and even work-related suicide. Medical consequences of
      workplace bullying may include an increase in health complaints such as neck
      pain, musculoskeletal complaints, acute pain, fibromyalgia, and cardiovascular
      symptoms. Finally, socioeconomic consequences of workplace bullying may include
      absenteeism due to sick days and unemployment. Clinicians in both mental health
      and primary care settings need to be alert to the associations between bullying
      in the workplace and these potential negative consequences, as patients may not
      disclose workplace maltreatment due to embarrassment or fears of retribution. 

PMID- 25852979
TI  - Path-integral methods for analyzing the effects of fluctuations in stochastic
      hybrid neural networks.
AB  - We consider applications of path-integral methods to the analysis of a stochastic
      hybrid model representing a network of synaptically coupled spiking neuronal
      populations. The state of each local population is described in terms of two
      stochastic variables, a continuous synaptic variable and a discrete activity
      variable. The synaptic variables evolve according to piecewise-deterministic
      dynamics describing, at the population level, synapses driven by spiking
      activity. The dynamical equations for the synaptic currents are only valid
      between jumps in spiking activity, and the latter are described by a jump Markov
      process whose transition rates depend on the synaptic variables. We assume a
      separation of time scales between fast spiking dynamics with time constant
      [Formula: see text] and slower synaptic dynamics with time constant tau. This
      naturally introduces a small positive parameter [Formula: see text], which can be
      used to develop various asymptotic expansions of the corresponding path-integral
      representation of the stochastic dynamics. First, we derive a variational
      principle for maximum-likelihood paths of escape from a metastable state (large
      deviations in the small noise limit [Formula: see text]). We then show how the
      path integral provides an efficient method for obtaining a diffusion
      approximation of the hybrid system for small epsilon. The resulting Langevin
      equation can be used to analyze the effects of fluctuations within the basin of
      attraction of a metastable state, that is, ignoring the effects of large
      deviations. We illustrate this by using the Langevin approximation to analyze the
      effects of intrinsic noise on pattern formation in a spatially structured hybrid
      network. In particular, we show how noise enlarges the parameter regime over
      which patterns occur, in an analogous fashion to PDEs. Finally, we carry out a
      [Formula: see text]-loop expansion of the path integral, and use this to derive
      corrections to voltage-based mean-field equations, analogous to the modified
      activity-based equations generated from a neural master equation. 

PMID- 25852980
TI  - A Mathematical Model of a Midbrain Dopamine Neuron Identifies Two Slow Variables
      Likely Responsible for Bursts Evoked by SK Channel Antagonists and Terminated by
      Depolarization Block.
AB  - Midbrain dopamine neurons exhibit a novel type of bursting that we call "inverted
      square wave bursting" when exposed to Ca(2+)-activated small conductance (SK)
      K(+) channel blockers in vitro. This type of bursting has three phases:
      hyperpolarized silence, spiking, and depolarization block. We find that two slow
      variables are required for this type of bursting, and we show that the three
      dimensional bifurcation diagram for inverted square wave bursting is a folded
      surface with upper (depolarized) and lower (hyperpolarized) branches. The
      activation of the L-type Ca(2+) channel largely supports the separation between
      these branches. Spiking is initiated at a saddle node on an invariant circle
      bifurcation at the folded edge of the lower branch and the trajectory spirals
      around the unstable fixed points on the upper branch. Spiking is terminated at a
      supercritical Hopf bifurcation, but the trajectory remains on the upper branch
      until it hits a saddle node on the upper folded edge and drops to the lower
      branch. The two slow variables contribute as follows. A second, slow component of
      sodium channel inactivation is largely responsible for the initiation and
      termination of spiking. The slow activation of the ether-a-go-go-related (ERG)
      K(+) current is largely responsible for termination of the depolarized plateau.
      The mechanisms and slow processes identified herein may contribute to bursting as
      well as entry into and recovery from the depolarization block to different
      degrees in different subpopulations of dopamine neurons in vivo. 

PMID- 25852981
TI  - A formalism for evaluating analytically the cross-correlation structure of a
      firing-rate network model.
AB  - We introduce a new formalism for evaluating analytically the cross-correlation
      structure of a finite-size firing-rate network with recurrent connections. The
      analysis performs a first-order perturbative expansion of neural activity
      equations that include three different sources of randomness: the background
      noise of the membrane potentials, their initial conditions, and the distribution
      of the recurrent synaptic weights. This allows the analytical quantification of
      the relationship between anatomical and functional connectivity, i.e. of how the
      synaptic connections determine the statistical dependencies at any order among
      different neurons. The technique we develop is general, but for simplicity and
      clarity we demonstrate its efficacy by applying it to the case of synaptic
      connections described by regular graphs. The analytical equations so obtained
      reveal previously unknown behaviors of recurrent firing-rate networks, especially
      on how correlations are modified by the external input, by the finite size of the
      network, by the density of the anatomical connections and by correlation in
      sources of randomness. In particular, we show that a strong input can make the
      neurons almost independent, suggesting that functional connectivity does not
      depend only on the static anatomical connectivity, but also on the external
      inputs. Moreover we prove that in general it is not possible to find a mean-field
      description a la Sznitman of the network, if the anatomical connections are too
      sparse or our three sources of variability are correlated. To conclude, we show a
      very counterintuitive phenomenon, which we call stochastic synchronization,
      through which neurons become almost perfectly correlated even if the sources of
      randomness are independent. Due to its ability to quantify how activity of
      individual neurons and the correlation among them depends upon external inputs,
      the formalism introduced here can serve as a basis for exploring analytically the
      computational capability of population codes expressed by recurrent neural
      networks. 

PMID- 25852983
TI  - Path integral methods for stochastic differential equations.
AB  - Stochastic differential equations (SDEs) have multiple applications in
      mathematical neuroscience and are notoriously difficult. Here, we give a self
      contained pedagogical review of perturbative field theoretic and path integral
      methods to calculate moments of the probability density function of SDEs. The
      methods can be extended to high dimensional systems such as networks of coupled
      neurons and even deterministic systems with quenched disorder. 

PMID- 25852982
TI  - Modeling focal epileptic activity in the Wilson-cowan model with depolarization
      block.
AB  - Measurements of neuronal signals during human seizure activity and evoked
      epileptic activity in experimental models suggest that, in these pathological
      states, the individual nerve cells experience an activity driven depolarization
      block, i.e. they saturate. We examined the effect of such a saturation in the
      Wilson-Cowan formalism by adapting the nonlinear activation function; we
      substituted the commonly applied sigmoid for a Gaussian function. We discuss
      experimental recordings during a seizure that support this substitution. Next we
      perform a bifurcation analysis on the Wilson-Cowan model with a Gaussian
      activation function. The main effect is an additional stable equilibrium with
      high excitatory and low inhibitory activity. Analysis of coupled local networks
      then shows that such high activity can stay localized or spread. Specifically, in
      a spatial continuum we show a wavefront with inhibition leading followed by
      excitatory activity. We relate our model simulations to observations of spreading
      activity during seizures. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version
      of this article (doi:10.1186/s13408-015-0019-4) contains supplementary material
      1.

PMID- 25852984
TI  - Unraveling the kinetic diversity of microbial 3-dehydroquinate dehydratases of
      shikimate pathway.
AB  - 3-Dehydroquinate dehydratase (DHQase) catalyzes the conversion of 3-dehydroquinic
      acid to 3-dehydroshikimic acid of the shikimate pathway. In this study, 3180
      prokaryotic genomes were examined and 459 DHQase sequences were retrieved. Based
      on sequence analysis and their original hosts, 38 DHQase genes were selected for
      chemical synthesis. The selected DHQases were translated into new DNA sequences
      according to the genetic codon usage bias by both Escherichia coli and
      Corynebacterium glutamicum. The new DNA sequences were customized for synthetic
      biological applications by adding Biobrick adapters at both ends and by removal
      of any related restriction endonuclease sites. The customized DHQase genes were
      successfully expressed in E. coli, and functional DHQases were obtained. Kinetic
      parameters of Km, kcat, and Vmax of DHQases were determined with a newly
      established high-throughput method for DHQase activity assay. Results showed that
      DHQases possessed broad strength of substrate affinities and catalytic
      capacities. In addition to the DHQase kinetic diversities, this study generated a
      DHQase library with known catalytic constants that could be applied to design
      artificial modules of shikimate pathway for metabolic engineering and synthetic
      biology. 

PMID- 25852985
TI  - Fe(III) mineral reduction followed by partial dissolution and reactive oxygen
      species generation during 2,4,6-trinitrotoluene transformation by the aerobic
      yeast Yarrowia lipolytica.
AB  - Understanding the factors that influence pollutant transformation in the presence
      of ferric (oxyhydr)oxides is crucial to the efficient application of different
      remediation strategies. In this study we determined the effect of goethite,
      hematite, magnetite and ferrihydrite on the transformation of 2,4,6
      trinitrotoluene (TNT) by Yarrowia lipolytica AN-L15. The presence of ferric
      (oxyhydr)oxides led to a small decrease in the rate of TNT removal. In all cases,
      a significant release of NO2 (-) from TNT and further NO2 (-) oxidation to NO3 (
      ) was observed. A fraction of the released NO2 (-) was abiotically decomposed to
      NO and NO2, and then NO was likely oxidized abiotically to NO2 by O2. ESR
      analysis revealed the generation of superoxide in the culture medium; its further
      protonation at low pH resulted in the formation of hydroperoxyl radical.
      Presumably, a fraction of NO released during TNT degradation reacted with
      superoxide and formed peroxynitrite, which was further rearranged to NO3 (-) at
      the acidic pH values observed in this study. A transformation and reduction of
      ferric (oxyhydr)oxides followed by partial dissolution (in the range of 7-86% of
      the initial Fe(III)) were observed in the presence of cells and TNT. Mossbauer
      spectroscopy showed some minor changes for goethite, magnetite and ferrihydrite
      samples during their incubation with Y. lipolytica and TNT. This study shows that
      i) reactive oxygen and nitrogen species generated during TNT transformation by Y.
      lipolytica participate in the abiotic conversion of TNT and ii) the presence of
      iron(III) minerals leads to a minor decrease in TNT transformation. 

PMID- 25852986
TI  - Surface functionalization by covalent immobilization of an innovative carvacrol
      derivative to avoid fungal biofilm formation.
AB  - Carvacrol, an aromatic terpenic compound, known to be antimicrobial was grafted
      onto gold surfaces via two strategies based on newly-synthesized cross-linkers
      involving either an ester bond which can be cleaved by microbial esterases, or a
      covalent ether link. Surface functionalizations were characterized at each step
      by reflection absorption infrared spectroscopy (RAIRS). The two functionalized
      gold samples both led to a loss of culturability of the yeast Candida albicans,
      higher than 65%, indicating that the activity of the freshly-designed surfaces
      was probably due to still covalently immobilized carvacrol. On the contrary, when
      a phenyl group replaced the terpenic moiety, the yeast culturability increased by
      about 30%, highlighting the specific activity of carvacrol grafted on the
      surfaces. Confocal microscopy analyses showed that the mode of action of the
      functionalized surfaces with the ester or the ether of carvacrol was, in both
      cases, fungicidal and not anti-adhesive. Finally, this study shows that
      covalently immobilization of terpenic compounds can be used to design promising
      antimicrobial surfaces. 

PMID- 25852987
TI  - Contribution of soil esterase to biodegradation of aliphatic polyester
      agricultural mulch film in cultivated soils.
AB  - The relationship between degradation speed of soil-buried biodegradable polyester
      film in a farmland and the characteristics of the predominant polyester-degrading
      soil microorganisms and enzymes were investigated to determine the BP-degrading
      ability of cultivated soils through characterization of the basal microbial
      activities and their transition in soils during BP film degradation. Degradation
      of poly(butylene succinate-co-adipate) (PBSA) film was evaluated in soil samples
      from different cultivated fields in Japan for 4 weeks. Both the degradation speed
      of the PBSA film and the esterase activity were found to be correlated with the
      ratio of colonies that produced clear zone on fungal minimum medium-agarose plate
      with emulsified PBSA to the total number colonies counted. Time-dependent change
      in viable counts of the PBSA-degrading fungi and esterase activities were
      monitored in soils where buried films showed the most and the least degree of
      degradation. During the degradation of PBSA film, the viable counts of the PBSA
      degrading fungi and the esterase activities in soils, which adhered to the PBSA
      film, increased with time. The soil, where the film was degraded the fastest,
      recorded large PBSA-degrading fungal population and showed high esterase activity
      compared with the other soil samples throughout the incubation period. Meanwhile,
      esterase activity and viable counts of PBSA-degrading fungi were found to be
      stable in soils without PBSA film. These results suggest that the higher the
      distribution ratio of native PBSA-degrading fungi in the soil, the faster the
      film degradation is. This could be due to the rapid accumulation of secreted
      esterases in these soils. 

PMID- 25852988
TI  - Alkyl hydroperoxide reductase enhances the growth of Leuconostoc mesenteroides
      lactic acid bacteria at low temperatures.
AB  - Lactic acid bacteria (LAB) can cause deterioration of food quality even at low
      temperatures. In this study, we investigated the cold-adaptation mechanism of a
      novel food spoilage LAB, Leuconostoc mesenteroides NH04 (NH04). L. mesenteroides
      was isolated from several spoiled cooked meat products at a high frequency in our
      factories. NH04 grew rapidly at low temperatures within the shelf-life period and
      resulted in heavy financial losses. NH04 grew more rapidly than related strains
      such as Leuconostoc mesenteroides NBRC3832 (NBRC3832) at 10 degrees C. Proteome
      analysis of NH04 demonstrated that this strain produces a homolog of alkyl
      hydroperoxide reductase--AhpC--the expression of which can be induced at low
      temperatures. The expression level of AhpC in NH04 was approximately 6-fold
      higher than that in NBRC3832, which was grown under the same conditions. Although
      AhpC is known to have an anti-oxidative role in various bacteria by catalyzing
      the reduction of alkyl hydroperoxide and hydrogen peroxide, the involvement of
      AhpC in cold adaptation of food spoilage bacteria was unclear. We introduced an
      expression plasmid containing ahpC into NBRC3832, which grows slower than NH04 at
      10 degrees C, and found that expression of AhpC enhanced growth. These results
      demonstrated that AhpC, which likely increases anti-oxidative capacity of LAB,
      plays an important role in their rapid growth at low temperatures. 

PMID- 25852989
TI  - Overexpression of PAD1 and FDC1 results in significant cinnamic acid
      decarboxylase activity in Saccharomyces cerevisiae.
AB  - The S. cerevisiae PAD1 gene had been suggested to code for a cinnamic acid
      decarboxylase, converting trans-cinnamic acid to styrene. This was suggested for
      the reason that the over-expression of PAD1 resulted in increased tolerance
      toward cinnamic acid, up to 0.6 mM. We show that by over-expression of the PAD1
      together with the FDC1 the cinnamic acid decarboxylase activity can be increased
      significantly. The strain over-expressing PAD1 and FDC1 tolerated cinnamic acid
      concentrations up to 10 mM. The cooperation of Pad1p and Fdc1p is surprising
      since the PAD1 has a mitochondrial targeting sequence and the FDC1 codes for a
      cytosolic protein. The cinnamic acid decarboxylase activity was also seen in the
      cell free extract. The activity was 0.019 MUmol per minute and mg of extracted
      protein. The overexpression of PAD1 and FDC1 resulted also in increased activity
      with the hydroxycinnamic acids ferulic acid, p-coumaric acid and caffeinic acid.
      This activity was not seen when FDC1 was overexpressed alone. An efficient
      cinnamic acid decarboxylase is valuable for the genetic engineering of yeast
      strains producing styrene. Styrene can be produced from endogenously produced L
      phenylalanine which is converted by a phenylalanine ammonia lyase to cinnamic
      acid and then by a decarboxylase to styrene. 

PMID- 25852990
TI  - Microbial production of Propionic and Succinic acid from Sorbitol using
      Propionibacterium acidipropionici.
AB  - Three sequential fermentative batches were carried out with cell recycle in four
      simultaneously operating bioreactors maintained at pH 6.5, 30 degrees C, and 100
      rpm. P. acidipropionici ATCC 4875 was able to produce propionic and succinic acid
      from sorbitol. The concentration of propionic acid decreased slightly from 39.5
      +/- 5.2 g L(-1) to 34.4 +/- 1.9 g L(-1), and that of succinic acid increased
      significantly from 6.1 +/- 2.1 g L(-1) to 14.8 +/- 0.9 g L(-1) through the
      sequential batches. In addition, a small amount of acetic acid was produced that
      decreased from 3.3 +/- 0.4 g L(-1) to 2.0 +/- 0.3 g L(-1) through the batches.
      The major yield for propionic acid was 0.613 g g(-1) in the first batch and
      succinic acid it was 0.212 g g(-1) in the third batch. The minor yield of acetic
      acid was 0.029 g g(-1), in the second and third batches. 

PMID- 25852991
TI  - Engineering of Saccharomyces cerevisiae for the production of poly-3-d
      hydroxybutyrate from xylose.
AB  - Poly-3-d-hydroxybutyrate (PHB) is a promising biopolymer naturally produced by
      several bacterial species. In the present study, the robust baker's yeast
      Saccharomyces cerevisiae was engineered to produce PHB from xylose, the main
      pentose found in lignocellulosic biomass. The PHB pathway genes from the well
      characterized PHB producer Cupriavidus necator were introduced in recombinant S.
      cerevisiae strains already capable of pentose utilization by introduction of the
      fungal genes for xylose utilization from the yeast Scheffersomyces stipitis. PHB
      production from xylose was successfully demonstrated in shake-flasks experiments,
      with PHB yield of 1.17 +/- 0.18 mg PHB g(-1) xylose. Under well-controlled fully
      aerobic conditions, a titer of 101.7 mg PHB L(-1) was reached within 48 hours,
      with a PHB yield of 1.99 +/- 0.15 mg PHB g(-1) xylose, thereby demonstrating the
      potential of this host for PHB production from lignocellulose. 

PMID- 25852992
TI  - Isolation of cellulolytic bacteria from the intestine of Diatraea saccharalis
      larvae and evaluation of their capacity to degrade sugarcane biomass.
AB  - As a strategy to find efficient lignocellulose degrading enzymes/microorganisms
      for sugarcane biomass pretreatment purposes, 118 culturable bacterial strains
      were isolated from intestines of sugarcane-fed larvae of the moth Diatraea
      saccharalis. All strains were tested for cellulolytic activity using soluble
      carboxymethyl cellulose (CMC) degrading assays or by growing bacteria on
      sugarcane biomass as sole carbon sources. Out of the 118 strains isolated thirty
      eight were found to possess cellulose degrading activity and phylogenetic studies
      of the 16S rDNA sequence revealed that all cellulolytic strains belonged to the
      phyla gamma-Proteobacteria, Actinobacteria and Firmicutes. Within the three
      phyla, species belonging to five different genera were identified (Klebsiella,
      Stenotrophomonas, Microbacterium, Bacillus and Enterococcus). Bacterial growth on
      sugarcane biomass as well as extracellular endo-glucanase activity induced on
      soluble cellulose was found to be highest in species belonging to genera Bacillus
      and Klebsiella. Good cellulolytic activity correlated with high extracellular
      protein concentrations. In addition, scanning microscopy studies revealed
      attachment of cellulolytic strains to different sugarcane substrates. The results
      of this study indicate the possibility to find efficient cellulose degrading
      enzymes and microorganisms from intestines of insect larvae feeding on sugarcane
      and their possible application in industrial processing of sugarcane biomass such
      as second generation biofuel production. 

PMID- 25852993
TI  - Enhanced xylose fermentation and ethanol production by engineered Saccharomyces
      cerevisiae strain.
AB  - We have recently demonstrated that heterologous expression of a bacterial xylose
      isomerase gene (xylA) of Burkholderia cenocepacia enabled a laboratorial
      Saccharomyces cerevisiae strain to ferment xylose anaerobically, without xylitol
      accumulation. However, the recombinant yeast fermented xylose slowly. In this
      study, an evolutionary engineering strategy was applied to improve xylose
      fermentation by the xylA-expressing yeast strain, which involved sequential batch
      cultivation on xylose. The resulting yeast strain co-fermented glucose and xylose
      rapidly and almost simultaneously, exhibiting improved ethanol production and
      productivity. It was also observed that when cells were grown in a medium
      containing higher glucose concentrations before being transferred to fermentation
      medium, higher rates of xylose consumption and ethanol production were obtained,
      demonstrating that xylose utilization was not regulated by catabolic repression.
      Results obtained by qPCR demonstrate that the efficiency in xylose fermentation
      showed by the evolved strain is associated, to the increase in the expression of
      genes HXT2 and TAL1, which code for a low-affinity hexose transporter and
      transaldolase, respectively. The ethanol productivity obtained after the
      introduction of only one genetic modification and the submission to a one-stage
      process of evolutionary engineering was equivalent to those of strains submitted
      to extensive metabolic and evolutionary engineering, providing solid basis for
      future applications of this strategy in industrial strains. 

PMID- 25852994
TI  - Characterization of the Kluyveromyces marxianus strain DMB1 YGL157w gene product
      as a broad specificity NADPH-dependent aldehyde reductase.
AB  - The open reading frame YGL157w in the genome of the yeast Kluyveromyces marxianus
      strain DMB1 encodes a putative uncharacterized oxidoreductase. However, this
      protein shows 46% identity with the Saccharomyces cerevisiae S288c NADPH
      dependent methylglyoxal reductase, which exhibits broad substrate specificity for
      aldehydes. In the present study, the YGL157w gene product (KmGRE2) was purified
      to homogeneity from overexpressing Escherichia coli cells and found to be a
      monomer. The enzyme was strictly specific for NADPH and was active with a wide
      variety of substrates, including aliphatic (branched-chain and linear) and
      aromatic aldehydes. The optimal pH for methylglyoxal reduction was 5.5. With
      methylglyoxal as a substrate, the optimal temperature for enzyme activity at pH
      5.5 was 45 degrees C. The enzyme retained more than 70% of its activity after
      incubation for 30 min at temperatures below 35 degrees C or at pHs between 5.5
      and 9.0. In addition, the KmGRE2-overexpressing E. coli showed improved growth
      when cultivated in cedar hydrolysate, as compared to cells not expressing the
      enzyme. Taken together, these results indicate that KmGRE2 is potentially useful
      as an inhibit decomposer in E. coli cells. 

PMID- 25852995
TI  - Strain and process development for poly(3HB-co-3HP) fermentation by engineered
      Shimwellia blattae from glycerol.
AB  - Poly(3-hydroxybytyrate-co-3-hydroxypropionate), poly(3HB-co-3HP), is a possible
      alternative to synthetic polymers such as polypropylene, polystyrene and
      polyethylene due to its low crystallinity and fragility. We already reported that
      recombinant strains of Shimwellia blattae expressing 1,3-propanediol
      dehydrogenase DhaT as well as aldehyde dehydrogenase AldD of Pseudomonas putida
      KT2442, propionate-CoA transferase Pct of Clostridium propionicum X2 and PHA
      synthase PhaC1 of Ralstonia eutropha H16 are able to accumulate up to 14.5%
      (wtPHA/wtCDW) of poly(3-hydroxypropionate), poly(3HP), homopolymer from glycerol
      as a sole carbon source (Appl Microbiol Biotechnol 98:7409-7422, 2014a). However,
      the cell density was rather low. In this study, we optimized the medium aiming at
      a more efficient PHA synthesis, and we engineered a S. blattae strain
      accumulating poly(3HB-co-3HP) with varying contents of the constituent 3
      hydroxypropionate (3HP) depending on the cultivation conditions. Consequently,
      7.12, 0.77 and 0.32 gPHA/L of poly(3HB-co-3HP) containing 2.1, 8.3 and 18.1 mol%
      3HP under anaerobic/aerobic (the first 24 hours under anaerobic condition,
      thereafter, aerobic condition), low aeration/agitation (the minimum stirring rate
      required in medium mixing and small amount of aeration) and anaerobic conditions
      (the minimum stirring rate required in medium mixing without aeration),
      respectively, were synthesized from glycerol by the genetically modified S.
      blattae ATCC33430 strains in optimized culture medium. 

PMID- 25852996
TI  - Induction, expression and characterisation of laccase genes from the marine
      derived fungal strains Nigrospora sp. CBMAI 1328 and Arthopyrenia sp. CBMAI 1330.
AB  - The capability of the fungi Nigrospora sp. CBMAI 1328 and Arthopyrenia sp. CBMAI
      1330 isolated from marine sponge to synthesise laccases (Lcc) in the presence of
      the inducer copper (1-10 MUM) was assessed. In a liquid culture medium
      supplemented with 5 MUM of copper sulphate after 5 days of incubation, Nigrospora
      sp. presented the highest Lcc activity (25.2 U.L(-1)). The effect of copper on
      Lcc gene expression was evaluated by reverse transcriptase polymerase chain
      reaction. Nigrospora sp. showed the highest gene expression of Lcc under the same
      conditions of Lcc synthesis. The highest Lcc expression by the Arthopyrenia sp.
      was detected at 96 h of incubation in absence of copper. Molecular approaches
      allowed the detection of Lcc isozymes and suggest the presence of at least two
      undescribed putative genes. Additionally, Lcc sequences from the both fungal
      strains clustered with other Lcc sequences from other fungi that inhabit marine
      environments. 

PMID- 25852997
TI  - Recombinant glucagon: a differential biological activity.
AB  - In Brazil, there is a growing demand for specialised pharmaceuticals, and the
      high cost of their importation results in increasing costs, reaching US$ 1.34
      billion in 2012 and US$ 1.61 billion in 2013. Worldwide expenses related to drugs
      could reach US$ 1.3 trillion in 2018, especially due to new treatments for
      hepatitis C and cancer. Specialised or high-cost pharmaceutical drugs used for
      the treatment of viral hepatitis, multiple sclerosis, HIV and diabetes are
      distributed free of charge by the Brazilian government. The glucagon peptide was
      included in this group of high-cost biopharmaceuticals in 2008. Although its main
      application is the treatment of hypoglycaemia in diabetic patients, it can also
      be used with patients in an alcoholic coma, for those patients with biliary tract
      pain, and as a bronchodilator. Therefore, in order to reduce biopharmaceutical
      production costs, the Brazilian government passed laws focusing on the
      development and increase of a National Pharmaceutical Industrial Centre,
      including the demand for the national production of glucagon. For that reason and
      given the importance and high cost of recombinant glucagon, the purpose of this
      study was to develop methods to improve production, purification and performance
      of the biological activity of recombinant glucagon. Glucagon was recombined into
      a plasmid vector containing a Glutathione S-transferase tag, and the peptide was
      expressed in a heterologous Escherichia coli system. After purification
      procedures and molecular analyses, the biological activity of this recombinant
      glucagon was examined using in vivo assays and showed a highly significant (p <
      0.00001) and prolonged effect on glucose levels when compared with the standard
      glucagon. The experimental procedure described here facilitates the high level
      production of recombinant glucagon with an extended biological activity. 

PMID- 25852998
TI  - Foam-free production of Surfactin via anaerobic fermentation of Bacillus subtilis
      DSM 10(T).
AB  - Surfactin is one of the most popular biosurfactants due to its numerous potential
      applications. The usually aerobic production via fermentation of Bacillus
      subtilis is accompanied by vigorous foaming which leads to complex constructions
      and great expense. Therefore it is reasonable to search for alternative foam-free
      production processes. The current study introduces a novel approach to produce
      Surfactin in a foam-free process applying a strictly anaerobic bioreactor
      cultivation. The process was performed several times with different glucose
      concentrations in mineral salt medium. The fermentations were analyzed regarding
      specific (qSurfactin, vol. qSurfactin) and overall product yields (YP/X, YP/S) as
      well as substrate utilization (YX/S). Fermentations in which 2.5 g/L glucose were
      employed proofed to be the most effective, reaching product yields of YP/X =
      0.278 g/g. Most interesting, the product yields exceeded classical aerobic
      fermentations, in which foam fractionation was applied. Additionally, values for
      specific production rate qSurfactin (0.005 g/(g?h)) and product yield per
      consumed substrate (YP/S = 0.033 g/g) surpass results of comparable foam-free
      processes. The current study introduces an alternative to produce a biosurfactant
      that overcomes the challenges of severe foaming and need for additional
      constructions. 

PMID- 25852999
TI  - The social and economic determinants of suicide in Canadian provinces.
AB  - BACKGROUND: In this paper we investigate the causal relationship between suicide
      and a variety of socioeconomic variables. We use a panel data set of Canadian
      provinces, 2000 - 2008, and a set of recent panel econometric techniques in order
      to account for a variety of statistical specification issues. RESULTS: We find
      that the social and economic determinants of suicide in Canadian provinces vary
      across total, male, and female counts (natural logarithms) and rates. We also
      find that the results vary depending on the econometric method employed. As such,
      separate analyses for males and females is necessary for a better understanding
      of the factors that impact suicide (consistent with previous research) and that
      the choice of statistical method impacts the results. Lastly, it is important to
      note the particular provinces are driving the results for particular
      socioeconomic variables. CONCLUSIONS: Such a result, if generalizable, has
      significant implications for suicide prevention policy.

PMID- 25853000
TI  - Socio-economic determinants of life expectancy in Nigeria (1980 - 2011).
AB  - Attainment of 70 years life expectancy by 2020 is one of the millennium
      development goals in Nigeria. This study examined the socio-economic determinants
      of life expectancy in Nigeria using data from 1980-2011. Judging from the
      endogeneity feature of the variables, A VAR and VECM frameworks were employed.
      Socio-economic features were proxy by secondary school enrolment, government
      expenditure on health, per capita income, unemployment rate and the Naira foreign
      exchange rate. It was found that, the conventional socio-economic variables such
      as per capita income, education and government expenditure on health considered
      to be highly effective in determining life expectancy of developing countries are
      not significant in the case of Nigeria. The study however suggests that, life
      expectancy in Nigeria could be improved if attention is given to quality of
      government health expenditure, unemployment and measures to halt the depreciation
      of the Nigerian Naira against major foreign currency. 

PMID- 25853001
TI  - Is healthcare a 'Necessity' or 'Luxury'? an empirical evidence from public and
      private sector analyses of South-East Asian countries?
AB  - South-East Asian Regional (SEAR) countries range from low- to middle-income
      countries and have considerable differences in mix of public and private sector
      expenditure on health. This study intends to estimate the income-elasticities of
      healthcare expenditure in public and private sectors separately for investigating
      whether healthcare is a 'necessity' or 'luxury' for citizens of these countries.
      Panel data from 9 SEAR countries over 16 years (1995-2010) were employed. Fixed-
      and random-effect models were fitted to estimate income-elasticity of public,
      private and total healthcare expenditure. Results showed that one percent point
      increase in GDP per capita increased private expenditure on healthcare by 1.128%,
      while public expenditure increased by only 0.412%. Inclusion of three-year lagged
      variables of GDP per capita in the models did not have remarkable influence on
      the findings. The citizens of SEAR countries consider healthcare as a necessity
      while provided through public sector and a luxury when delivered by private
      sector. By increasing the public provisions of healthcare, more redistribution of
      healthcare resources can be ensured, which can accelerate the journey of SEAR
      countries towards universal health coverage. 

PMID- 25853002
TI  - A reconstruction of a medical history from administrative data: with an
      application to the cost of skin cancer.
AB  - The medical record is a repository of clinical data, which can greatly enhance
      the quality of health and healthcare analysis. Administrative data are collected
      for the purpose of billing and reimbursement, and are valued by health
      researchers because the data are routinely audited to maintain accurate financial
      records. However, the quantity of incorporated clinical data can be variable. In
      this paper we reconstruct the medical record from health service invoices to
      estimate the cost of treating keratinocytic cancer (KC). The data from an
      epidemiological survey were linked to an administrative data set supplied by the
      national health insurer. A matched sampling technique with multivariable analysis
      was used to estimate cost. A KC treatment was identified with 42 service codes
      which explicitly nominated treatment of a KC. Algorithms identifying comorbities
      potentially correlated with KC were constructed from the service codes. The
      annual cost of a KC treatment was estimated to be AU$667 per individual. The
      average cost of explicit KC treatments was AU$231, while the cost of generic
      procedures used to treat KC was AU$436. Our ability to accurately control for the
      medical history enabled our analysis to quantify and describe the constituent
      costs of KC treatment. 

PMID- 25853003
TI  - The Nigeria wealth distribution and health seeking behaviour: evidence from the
      2012 national HIV/AIDS and reproductive health survey.
AB  - BACKGROUND: Recently, Nigeria emerged as the largest economy in Africa and the
      26th in the world. However, a pertinent question is how this new economic status
      has impacted on the wealth and health of her citizens. There is a dearth of
      empirical study on the wealth distribution in Nigeria which could be important in
      explaining the general disparities in their health seeking behavior. An adequate
      knowledge of Nigeria wealth distribution will no doubt inform policy makers in
      their decision making to improve the quality of life of Nigerians. METHOD: This
      study is a retrospective analysis of the assets of household in Nigeria collected
      during the 2012 National HIV/AIDS and Reproductive Health Survey (NARHS Plus 2).
      We used the principal component analysis methods to construct wealth quintiles
      across households in Nigeria. At 5% significance level, we used ANOVA to
      determine differences in some health outcomes across the WQs and chi-square test
      to assess association between WQs and some reproductive health seeking
      behaviours. RESULT: The wealth quintiles were found to be internally valid and
      coherent. However, there is a wide gap in the reproductive health seeking
      behavior of household members across the wealth quintiles with members of
      households in lower quintiles having lesser likelihood (33.0%) to receive
      antenatal care than among those in the highest quintiles (91.9%). While only 3%
      were currently using modern contraceptives in the lowest wealth quintile, it was
      17.4% among the highest wealth quintile (p < 0.05). CONCLUSION: The wealth
      quintiles showed a great disparity in the standard of living of Nigerian
      households across geo-political zones, states and rural-urban locations which had
      greatly influenced household health seeking behavior.

PMID- 25853004
TI  - Binge drinking and alcohol prices: a systematic review of age-related results
      from econometric studies, natural experiments and field studies.
AB  - BACKGROUND: Heavy episodic ("binge") drinking of alcohol has serious public
      health implications, especially for youth and young adults. Previous summaries
      and surveys have failed to address in a comprehensive manner the effects of
      alcohol prices on binge drinking by gender or age group. METHODS: A qualitative
      systematic review is performed for effects of alcohol prices (or tax surrogates)
      on binge drinking for three age groups: youth, young adults, and adults. Outcomes
      examined include binge participation, intensity and frequency. Criteria for data
      collection and potential sources of bias are discussed, including adequacy of
      price data. Price-binge relationships are judged using a 95% confidence interval
      (p <= 0.05) for statistical significance. RESULTS: Fifty-six relevant econometric
      studies were found, with studies and results distributed equally among three age
      groups. Also found were five natural experiments for tax reductions and six field
      studies. Null results or mixed results are found in more than half of the
      studies. The body of evidence indicates that binge drinkers are not highly
      responsive to increased prices. Non-responsiveness holds generally for younger
      and older drinkers and for male and female binge drinkers alike. A limitation of
      the current literature is that results are only available for higher-income
      countries. CONCLUSIONS: Increased alcohol taxes or prices are unlikely to be
      effective as a means to reduce binge drinking, regardless of gender or age group.

PMID- 25853005
TI  - The Role of decision-analytic modelling in German health technology assessments.
AB  - BACKGROUND: Decision-analytic modelling (DAM) has become a widespread method in
      health technology assessments (HTA), but the extent to which modelling is used
      differs among international HTA institutions. In Germany, the use of DAM is
      optional within HTAs of the German Institute of Medical Documentation and
      Information (DIMDI). Our study examines the use of DAM in DIMDI HTA reports and
      its effect on the quality of information provided for health policies. METHODS: A
      review of all DIMDI HTA reports (from 1998 to September 2012) incorporating an
      economic assessment was performed. All included reports were divided into two
      groups: HTAs with DAM and HTAs without DAM. In both groups, reports were
      categorized according to the quality of information provided for healthcare
      decision making. RESULTS: Of the sample of 107 DIMDI HTA reports, 17 (15.9%) used
      DAM for economic assessment. In the group without DAM, conclusions were limited
      by the quality of economic information in 51.1% of the reports, whereas we did
      not find limited conclusions in the group with DAM. Furthermore, 24 reports
      without DAM (26.7%) stated that using DAM would likely improve the quality of
      information of the economic assessment. CONCLUSION: The use of DAM techniques can
      improve the quality of HTAs in Germany. When, after a systematic review of
      existing literature within a HTA, it is clear that DAM is likely to positively
      affect the quality of the economic assessment DAM should be used.

PMID- 25853006
TI  - Effect of timely initiation of breastfeeding on child health in Ghana.
AB  - BACKGROUND: Early initiation of breastfeeding and exclusive breastfeeding
      practices have been argued to be one of the important ways of ensuring child
      health. Unfortunately, owing to modernization, most nursing mothers fail to
      adhere to such practices. This is believed to be a factor contributory to poor
      child health in Ghana. Thus, this study investigated the effect of timely
      initiation of breastfeeding on child health in Ghana. METHODS: Cross sectional
      data using secondary data based on the positivism approach to research was
      employed. The Ordinary least squares and the Instrumental variables approach were
      used in estimating the effect of breastfeeding and other socio demographic
      indicators on the health of the child. Data for the study was sourced from the
      2008 round of the Ghana Demographic and Health Survey. RESULTS: The results
      indicate that timely initiation of breastfeeding, both immediately and hours
      after birth are important factors that influence the child's health.
      Additionally, factors such as the wealth of the household, mother's education,
      age and size of the child at birth and age of the mother are important factors
      that also influence the health of the child in Ghana. CONCLUSION: The findings
      imply that efforts should be made on encouraging appropriate breastfeeding
      practices among nursing mothers to ensure proper child development and growth in
      Ghana.

PMID- 25853007
TI  - Transcriptional response in normal mouse tissues after i.v. (211)At
      administration - response related to absorbed dose, dose rate, and time.
AB  - BACKGROUND: In cancer radiotherapy, knowledge of normal tissue responses and
      toxicity risks is essential in order to deliver the highest possible absorbed
      dose to the tumor while maintaining normal tissue exposure at non-critical
      levels. However, few studies have investigated normal tissue responses in vivo
      after (211)At administration. In order to identify molecular biomarkers of
      ionizing radiation exposure, we investigated genome-wide transcriptional
      responses to (very) low mean absorbed doses from (211)At in normal mouse tissues.
      METHODS: Female BALB/c nude mice were intravenously injected with 1.7 kBq (211)At
      and killed after 1 h, 6 h, or 7 days or injected with 105 or 7.5 kBq and killed
      after 1 and 6 h, respectively. Controls were mock-treated. Total RNA was
      extracted from tissue samples of kidney cortex and medulla, liver, lungs, and
      spleen and subjected to microarray analysis. Enriched biological processes were
      categorized after cellular function based on Gene Ontology terms. RESULTS:
      Responses were tissue-specific with regard to the number of significantly
      regulated transcripts and associated cellular function. Dose rate effects on
      transcript regulation were observed with both direct and inverse trends. In
      several tissues, Angptl4, Per1 and Per2, and Tsc22d3 showed consistent transcript
      regulation at all exposure conditions. CONCLUSIONS: This study demonstrated
      tissue-specific transcriptional responses and distinct dose rate effects after
      (211)At administration. Transcript regulation of individual genes, as well as
      cellular responses inferred from enriched transcript data, may serve as
      biomarkers in vivo. These findings expand the knowledge base on normal tissue
      responses and may help to evaluate and limit side effects of radionuclide
      therapy.

PMID- 25853008
TI  - Molecular imaging of angiogenesis after myocardial infarction by (111)In-DTPA
      cNGR and (99m)Tc-sestamibi dual-isotope myocardial SPECT.
AB  - BACKGROUND: CD13 is selectively upregulated in angiogenic active endothelium and
      can serve as a target for molecular imaging tracers to non-invasively visualise
      angiogenesis in vivo. Non-invasive determination of CD13 expression can
      potentially be used to monitor treatment response to pro-angiogenic drugs in
      ischemic heart disease. CD13 binds peptides and proteins through binding to
      tripeptide asparagine-glycine-arginine (NGR) amino acid residues. Previous
      studies using in vivo fluorescence microscopy and magnetic resonance imaging
      indicated that cNGR tripeptide-based tracers specifically bind to CD13 in
      angiogenic vasculature at the border zone of the infarcted myocardium. In this
      study, the CD13-binding characteristics of an (111)In-labelled cyclic NGR peptide
      (cNGR) were determined. To increase sensitivity, we visualised (111)In-DTPA-cNGR
      in combination with (99m)Tc-sestamibi using dual-isotope SPECT to localise CD13
      expression in perfusion-deficient regions. METHODS: Myocardial infarction (MI)
      was induced in Swiss mice by ligation of the left anterior descending coronary
      artery (LAD). (111)In-DTPA-cNGR and (99m)Tc-sestamibi dual-isotope SPECT imaging
      was performed 7 days post-ligation in MI mice and in control mice. In addition,
      ex vivo SPECT imaging on excised hearts was performed, and biodistribution of
      (111)In-DTPA-cNGR was determined using gamma counting. Binding specificity of
      (111)In-DTPA-cNGR to angiogenic active endothelium was determined using the
      Matrigel model. RESULTS: Labelling yield of (111)In-DTPA-cNGR was 95% to 98% and
      did not require further purification. In vivo, (111)In-DTPA-cNGR imaging showed a
      rapid clearance from non-infarcted tissue and a urinary excretion of 82% of the
      injected dose (I.D.) 2 h after intravenous injection in the MI mice. Specific
      binding of (111)In-DTPA-cNGR was confirmed in the Matrigel model and, moreover,
      binding was demonstrated in the infarcted myocardium and infarct border zone.
      CONCLUSIONS: Our newly designed and developed angiogenesis imaging probe (111)In
      DTPA-cNGR allows simultaneous imaging of CD13 expression and perfusion in the
      infarcted myocardium and the infarct border zone by dual-isotope micro-SPECT
      imaging.

PMID- 25853009
TI  - Role of CD8-positive cells in radioimmunotherapy utilizing (177)Lu-mAbs in an
      immunocompetent rat colon carcinoma model.
AB  - BACKGROUND: CD8-positive cells might play a crucial role in the therapeutic
      response to radiation, which has however not been investigated in
      radioimmunotherapy (RIT). The aim of this study was to evaluate whether cytotoxic
      T cells affect the response of established tumors and, above all, if they delay
      or prevent the development of distant metastases after RIT, using an
      immunocompetent syngeneic rat colon carcinoma model. METHODS: The cytotoxic T
      cells were depleted in 15 rats by anti-CD8 before the injection of the
      radioimmunoconjugate (400 MBq/kg body weight (177)Lu-BR96, which binds to the
      tumor-associated antigen Lewis Y). Fifteen other rats were treated with RIT only.
      Both groups were followed for 99 days. Blood samples were collected at least once
      weekly, and tumors were monitored twice weekly. RESULTS: Twenty-nine of the 30
      animals exhibited local complete response. The non-responder was treated with
      anti-CD8 and RIT but succumbed later due to metastases. Five animals in the group
      given anti-CD8 + RIT were sacrificed due to metastatic disease, and 4 additional
      animals were found to have metastases at autopsy. In the group given RIT, 4
      animals developed metastatic disease, but no metastases were found in the
      remaining 11 animals at autopsy. Thus, at the end of the study, 6 animals in the
      anti-CD8 + RIT group were free from metastases, while 11 were free from
      metastases in the group receiving RIT. CD3(+)CD4(-)CD8(+) lymphocytes were
      consistently depleted by the anti-CD8 treatment. The myelosuppression was
      otherwise similar in the two groups. The initial depletion of CD8-positive cells
      in our syngeneic rat colon carcinoma model resulted in a higher frequency of
      animals developing metastases. CONCLUSIONS: Depletion of CD8-positive cells
      during RIT in an immunocompetent rat tumor model might influence the number of
      animals developing metastases, indicating that the immune system may be important
      in the long-term outcome of RIT.

PMID- 25853010
TI  - Identifying erlotinib-sensitive non-small cell lung carcinoma tumors in mice
      using [(11)C]erlotinib PET.
AB  - BACKGROUND: Non-small cell lung carcinoma (NSCLC) represents approximately 80% of
      lung cancer cases, and over 60% of these tumors express the epidermal growth
      factor receptor (EGFR). Activating mutations in the tyrosine kinase (TK) domain
      of the EGFR are detected in 10% to 30% of NSCLC patients, and evidence of their
      presence is a prerequisite for initiation of first-line therapy with selective TK
      inhibitors (TKIs), such as gefitinib and erlotinib. To date, the selection of
      candidate patients for first-line treatment with EGFR TKIs requires an invasive
      tumor biopsy to affirm the mutational status of the receptor. This study was
      designed to evaluate whether positron emission tomography (PET) of NSCLC tumor
      bearing mice using [(11)C]erlotinib could distinguish erlotinib-sensitive from
      erlotinib-insensitive or erlotinib-resistant tumors. METHODS: Four human NSCLC
      cell lines were employed, expressing either of the following forms of the EGFR:
      (i) the wild-type receptor (QG56 cells), (ii) a mutant with an exon 19 in-frame
      deletion (HCC827 cells), (iii) a mutant with the exon 21 L858R point mutation
      (NCI-H3255 cells), and (iv) a double mutant harboring the L858R and T790M
      mutations (NCI-H1975 cells). Sensitivity of each cell line to the anti
      proliferative effect of erlotinib was determined in vitro. In vivo PET imaging
      studies following i.v. injection of [(11)C]erlotinib were carried out in nude
      mice bearing subcutaneous (s.c.) xenografts of the four cell lines. RESULTS:
      Cells harboring activating mutations in the EGFR TK domain (HCC827 and NCI-H3255)
      were approximately 1,000- and 100-fold more sensitive to erlotinib treatment in
      vitro, respectively, compared to the other two cell lines. [(11)C]Erlotinib PET
      scans could differentiate erlotinib-sensitive tumors from insensitive (QG56) or
      resistant (NCI-H1975) tumors already at 12 min after injection. Nonetheless, the
      uptake in HCC827 tumors was significantly higher than that in NCI-H3255, possibly
      reflecting differences in ATP and erlotinib affinities between the EGFR mutants.
      CONCLUSIONS: [(11)C]Erlotinib imaging in mice differentiates erlotinib-sensitive
      NSCLC tumors from erlotinib-insensitive or erlotinib-resistant ones.

PMID- 25853011
TI  - The ultimate radiochemical nightmare: upon radio-iodination of Botulinum
      neurotoxin A, the introduced iodine atom itself seems to be fatal for the
      bioactivity of this macromolecule.
AB  - BACKGROUND: Botulinum neurotoxin A (BoNT-A) is a highly neurotoxic drug and
      frequently used in patients. Knowledge on the optimal way of administration of
      BoNT-A and its subsequent distribution is still rather limited. An accurate
      method for monitoring these processes might be the use of radiolabelled BoNT-A.
      In this paper, we report our feasibility study on labelling BoNT-A with high-dose
      iodine-125 ((125)I) via IODOGEN-coated BoNT-A method. METHODS: Using cetuximab as
      model substrate for BoNT-A, a miniaturization of the IODOGEN-coated mAb method
      was developed with special attention to the minimum required amount of the
      oxidant IODOGEN, while the amount of substrate, reaction volume and reaction time
      were downsized. Labelling efficiency and radiochemical purity were determined by
      TLC, integrity by SDS-PAGE and HPLC and immunoreactivity by cell-binding assay.
      BoNT-A (50 MUg) was labelled with (125)I by coating with 2.5 MUg IODOGEN, in a
      total reaction volume of 250 MUL and a reaction time of 90 s. (125)I-BoNT-A was
      purified by size exclusion chromatography (PD10 column) using ascorbic acid
      solution (5 mg/ml, pH = 5) as eluent. Quality analysis of (125)I-BoNT-A was
      performed by an in vitro bladder strip model, an electrochemiluminescence assay
      and an Endopep assay. RESULTS: Cetuximab (50 MUg) labelling with (125)I (15 to
      150 MBq) resulted in a labelling efficiency of 70% to 80%, a radiochemical purity
      of >99%, an immunoreactivity of >95% and a retained integrity on SDS; HPLC
      analysis revealed partly affected integrity when 110 to 150 MBq (125)I was used,
      i.e. when the averaged I/mAb molar ratio exceeded 3. Addition of HEPES (20 mM)
      and lactose (1.25%) (lyophilized BoNT-A contains HEPES and lactose) decreased the
      labelling efficiency to 44% to 54%. BoNT-A (50 MUg) labelling with (125)I (97.2
      to 98.3 MBq) resulted in labelling efficiency of 51% to 52% with a radiochemical
      purity >98.5%, a specific activity of 150.5 to 152.9 MBq/nmol and an I/BoNT-A
      molar ratio of 1.86 to 1.90. The in vitro bladder strip model showed no
      bioactivity of (125)I-BoNT-A when compared to unlabelled BoNT-A. The
      electrochemiluminescence and Endopep assay demonstrated around 10% and 15%
      bioactivity of (125)I-BoNT-A compared to unlabelled BoNT-A, respectively. The
      remaining bioactivity correlates within the Poisson distribution with the amount
      of BoNT-A molecules that does not bear an iodine atom. CONCLUSIONS: BoNT-A was
      successfully radio-iodinated with an activity high enough to enable in vivo
      measurement of nanograms of BoNT-A, which could be used in studying optimization
      of administration techniques of BoNT-A. The bioactivity of a BoNT-A molecule is,
      however, lost upon the introduction of an iodine atom into the tyrosine moiety of
      this sensitive molecule.

PMID- 25853012
TI  - An assessment of the characteristics and quality of diagnostic accuracy studies
      for positron emission tomography conducted in Japan: a systematic review.
AB  - BACKGROUND: Systematic evaluations of the diagnostic accuracy of positron
      emission tomography (PET) imaging have been widely conducted in many countries.
      Although Japan's total number of PET units is the second highest in the world,
      very limited effort has been made to systematically assess the methodological
      quality of PET studies in Japan. We performed a systematic review to assess the
      characteristics and quality of PET diagnostic accuracy studies conducted in Japan
      and to analyze the factors related to their quality. METHODS: All PET studies
      conducted in Japan were identified using MEDLINE and the Japan Medical Abstract
      Society Database. The characteristics of the Japanese studies were examined and
      their methodological quality evaluated by the standardized quality assessment of
      diagnostic accuracy studies (QUADAS) tool. We compared the quality of studies
      indexed in MEDLINE with non-indexed studies, followed by a comparison of the
      studies' conclusions with those of international health technology assessment
      (HTA) reports. RESULTS: A total of 138 studies were identified. Half of them were
      not indexed in MEDLINE. The mean quality score of the Japanese studies was 6.7
      and the proportion of high-quality studies (with a quality score higher than 8)
      was 32.6%. A significant difference was observed in several quality items between
      MEDLINE-indexed and non-indexed studies, although there was no difference in
      total quality score. Three variables (i.e., target diseases, publication year,
      and study type) were identified as factors related to the quality of the studies.
      Conclusions of Japanese studies relating to several target diseases were
      relatively consistent with international assessments. CONCLUSIONS: Although a
      considerable number of diagnostic accuracy studies of PET have been conducted in
      Japan, a substantial proportion of high-quality studies were not indexed in
      international databases. High-quality Japanese studies, therefore, should be
      searched using Japanese databases and assessed by systematic reviews and HTA
      conducted internationally.

PMID- 25853013
TI  - Comparison of 4'-[methyl-(11)C]thiothymidine ((11)C-4DST) and 3'-deoxy-3'
      [(18)F]fluorothymidine ((18)F-FLT) PET/CT in human brain glioma imaging.
AB  - BACKGROUND: 3'-deoxy-3'-[(18)F]fluorothymidine ((18)F-FLT) has been used to
      evaluate tumor malignancy and cell proliferation in human brain gliomas. However,
      (18)F-FLT has several limitations in clinical use. Recently, (11)C-labeled
      thymidine analogue, 4'-[methyl-(11)C]thiothymidine ((11)C-4DST), became available
      as an in vivo cell proliferation positron emission tomography (PET) tracer. The
      present study was conducted to evaluate the usefulness of (11)C-4DST PET in the
      diagnosis of human brain gliomas by comparing with the images of (18)F-FLT PET.
      METHODS: Twenty patients with primary and recurrent brain gliomas underwent (18)F
      FLT and (11)C-4DST PET scans. The uptake values in the tumors were evaluated
      using the maximum standardized uptake value (SUVmax), the tumor-to-normal tissue
      uptake (T/N) ratio, and the tumor-to-blood uptake (T/B) ratio. These values were
      compared among different glioma grades. Correlation between the Ki-67 labeling
      index and the uptake values of (11)C-4DST and (18)F-FLT in the tumor was
      evaluated using linear regression analysis. The relationship between the
      individual (18)F-FLT and (11)C-4DST uptake values in the tumors was also
      examined. RESULTS: (11)C-4DST uptake was significantly higher than that of (18)F
      FLT in the normal brain. The uptake values of (11)C-4DST in the tumor were
      similar to those of (18)F-FLT resulting in better visualization with (18)F-FLT.
      No significant differences in the uptake values of (18)F-FLT and (11)C-4DST were
      noted among different glioma grades. Linear regression analysis showed a
      significant correlation between the Ki-67 labeling index and the T/N ratio of
      (11)C-4DST (r = 0.50, P < 0.05) and (18)F-FLT (r = 0.50, P < 0.05). Significant
      correlations were also found between the Ki-67 labeling index and the T/B ratio
      of (11)C-4DST (r = 0.52, P < 0.05) and (18)F-FLT (r = 0.55, P < 0.05). A highly
      significant correlation was observed between the individual T/N ratio of (11)C
      4DST and (18)F-FLT in the tumor (r = 0.79, P = 0.0001). CONCLUSIONS: The present
      study demonstrates that (11)C-4DST is useful for the imaging of human brain
      gliomas with PET. A relatively higher background uptake of (11)C-4DST in the
      normal brain compared to (18)F-FLT limits the detection of low-tracer-uptake
      tumors. Moreover, no superiority was found in (11)C-4DST over (18)F-FLT in the
      evaluation of cell proliferation.

PMID- 25853014
TI  - (64)Cu-DOTA-trastuzumab PET imaging and HER2 specificity of brain metastases in
      HER2-positive breast cancer patients.
AB  - BACKGROUND: The purpose of this study was to determine whether brain metastases
      from HER2-positive breast cancer could be detected noninvasively using positron
      emission tomography (PET) with (64)Cu-1,4,7,10-tetraazacyclododecane-1,4,7,10
      tetraacetic acid (DOTA)-trastuzumab. METHODS: PET was performed on five patients
      with brain metastases from HER2-positive breast cancer, at 24 or 48 h after the
      injection of approximately 130 MBq of the probe (64)Cu-DOTA-trastuzumab.
      Radioactivity in metastatic brain tumors was evaluated based on PET images in
      five patients. Autoradiography, immunohistochemistry (IHC), and liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) analysis were performed in one
      surgical case to confirm HER2 specificity of (64)Cu-DOTA-trastuzumab. RESULTS:
      Metastatic brain lesions could be visualized by (64)Cu-DOTA-trastuzumab PET in
      all of five cases, which might indicated that trastuzumab passes through the
      blood-brain barrier (BBB). The HER2 specificity of (64)Cu-DOTA-trastuzumab was
      demonstrated in one patient by autoradiography, immunohistochemistry, and LC
      MS/MS. CONCLUSIONS: Cu-DOTA-trastuzumab PET could be a potential noninvasive
      procedure for serial identification of metastatic brain lesions in patients with
      HER2-positive breast cancer. TRIAL REGISTRATION: UMIN000004170.

PMID- 25853015
TI  - SPECT imaging of glioma with radioiodinated CLINDE: evidence from a mouse GL26
      glioma model.
AB  - BACKGROUND: Recent research has demonstrated the potential of 18-kDa translocator
      protein (TSPO) to serve as a target for nuclear imaging of gliomas. The aim of
      this study was to evaluate SPECT imaging of GL26 mouse glioma using
      radioiodinated CLINDE, a TSPO-specific tracer. METHODS: GL26 cells, previously
      transfected with an enhanced green fluorescent protein (EGFP)-expressing
      lentivirus, were stereotactically implanted in the striatum of C57/Bl6 mice. At 4
      weeks post-injection, dynamic SPECT scans with [(123)I]CLINDE were performed. A
      displacement study assessed specificity of tracer binding. SPECT images were
      compared to results of autoradiography, fluorescence microscopy, in situ nucleic
      acid hybridization, histology, and immunohistochemistry. Western blotting was
      performed to verify TSPO production by the tumor. RESULTS: Specific uptake of
      tracer by the tumor is observed with a high signal-to-noise ratio. Tracer uptake
      by the tumor is indeed 3.26 +/- 0.32 times higher than that of the contralateral
      striatum, and 78% of the activity is displaceable by unlabeled CLINDE. Finally,
      TSPO is abundantly expressed by the GL26 cells. CONCLUSIONS: The present study
      demonstrates the feasibility of [(123)I]CLINDE SPECT in translational studies and
      underlines its potential for clinical glioma SPECT imaging.

PMID- 25853016
TI  - Heterogeneity of intratumoral (111)In-ibritumomab tiuxetan and (18)F-FDG
      distribution in association with therapeutic response in radioimmunotherapy for B
      cell non-Hodgkin's lymphoma.
AB  - BACKGROUND: The purpose of this study was to quantitatively evaluate the tumor
      accumulation and heterogeneity of (111)In-ibritumomab tiuxetan (Zevalin(r)) and
      tumor accumulation of (18)F-fluoro-deoxyglucose (FDG) and compare them to the
      tumor response in B-cell non-Hodgkin's lymphoma patients receiving (90)Y
      ibritumomab tiuxetan (Zevalin(r)) therapy. METHODS: Sixteen patients with
      histologically confirmed non-Hodgkin's B-cell lymphoma who underwent (90)Y
      ibritumomab tiuxetan therapy along with (111)In-ibritumomab tiuxetan single
      photon emission computerized tomography (SPECT)/CT and FDG positron emission
      tomography (PET)/CT were enrolled in this retrospective study. On pretherapeutic
      FDG PET/CT images, the maximum standardized uptake value (SUVmax) was measured.
      On SPECT/CT images, a percentage of the injected dose per gram (%ID/g) and SUVmax
      of (111)In-ibritumomab tiuxetan were measured at 48 h after its administration.
      The skewness and kurtosis of the voxel distribution were calculated to evaluate
      the intratumoral heterogeneity of tumor accumulation. As another intratumoral
      heterogeneity index, cumulative SUV-volume histograms describing the percentage
      of the total tumor volume above the percentage thresholds of pretherapeutic FDG
      and (111)In-ibritumomab tiuxetan SUVmax (area under the curve of the cumulative
      SUV histograms (AUC-CSH)) were calculated. All lesions (n = 42) were classified
      into responders and non-responders lesion-by-lesion on pre- and post-therapeutic
      CT images. RESULTS: A positive correlation was observed between the FDG SUVmax
      and accumulation of (111)In-ibritumomab tiuxetan in lesions. A significant
      difference in pretherapeutic FDG SUVmax was observed between responders and non
      responders, while no significant difference in (111)In-ibritumomab tiuxetan
      SUVmax was observed between the two groups. In contrast, voxel distribution of
      FDG demonstrated no significant differences in the three heterogeneity indices
      between responders and non-responders, while (111)In-ibritumomab tiuxetan
      demonstrated skewness of 0.58 +/- 0.16 and 0.73 +/- 0.24 (p < 0.05), kurtosis of
      2.39 +/- 0.32 and 2.78 +/- 0.53 (p < 0.02), and AUC-CSH of 0.37 +/- 0.04 and 0.34
      +/- 0.05 (p < 0.05) for responders and non-responders. CONCLUSIONS:
      Pretherapeutic FDG accumulation was predictive of the tumor response in (90)Y
      ibritumomab tiuxetan therapy. The heterogeneity of the intratumoral distribution
      rather than the absolute level of (111)In-ibritumomab tiuxetan was correlated
      with the tumor response.

PMID- 25853017
TI  - The effect of radiation exposure on multidrug resistance: in vitro and in vivo
      studies using non-small lung cancer cells.
AB  - BACKGROUND: Technetium-99m methoxyisobutylisonitrile (Tc MIBI) is a substrate
      with the same uptake kinetics as doxorubicin. Multidrug resistance (MDR) is a
      mechanism that impedes chemotherapy of non-small cell lung cancer (NSCLC). We
      examined the effect of radiation exposure on MDR in NSCLC and the synergy between
      an MDR modulator, GG918, and radiation, using (99m)Tc MIBI in vitro and
      doxorubicin in vivo. METHODS: In vitro NSCLC cells (H1299) were exposed to
      radiation (3-, 6-, and 9-Gy-irradiated groups) alongside a not-irradiated (0 Gy)
      group. Technetium-99 metastable methoxyisobutylisonitrile ((99m)Tc MIBI) was
      administered to cell suspensions at 48 h after irradiation. Cell radioactivity
      was measured, and C in/C out ratios were calculated and compared. NSCLC cells
      were also subcutaneously transplanted into the left thigh of nude mice, which
      were subsequently raised for 2 weeks. Two groups of mice were used: mice exposed
      to irradiation (9-Gy-irradiated) and those that were not (not-irradiated).
      Doxorubicin was administered through the caudal vein at 48 h after the
      irradiation. Using an in vivo imaging system, intratumoural photon counts were
      measured. To determine the synergy between the MDR modulator and 3- or 6-Gy
      irradiation, the final GG918 concentration was determined: 0.1 MUM (N-H, 3-H, and
      6-H groups), 0.001 MUM (N-L, 3-L, and 6-L groups), and 0 MUM (N-0, 3-0, and 6-0
      groups). C in/C out ratios were calculated and compared among the groups.
      RESULTS: C in/C out after 6- or 9-Gy irradiation was significantly higher than
      that of the not-irradiated group (0 Gy). In vivo, fluorescence photon counts were
      significantly higher in the tumours of 9-Gy-irradiated mice, up to 270 min after
      administration of doxorubicin, as compared to the not-irradiated mice. The C in/C
      out ratio in the N-H, 3-H, and 6-H groups was significantly higher than that in
      the N-0, 3-0, and 6-0 groups. There was no significant difference between C in/C
      out in the N-L group and that of the N-0 group. However, the C in/C out ratio in
      the 3-L and 6-L groups was significantly higher than that in the 3-0 and 6-0
      groups. CONCLUSIONS: Irradiation decreased MDR in NSCLC cells. In combination
      with a low-dose MDR modulator, GG918, MDR transport function was synergistically
      reduced 48 h post-irradiation.

PMID- 25853018
TI  - The diagnostic accuracy of dopamine transporter SPECT imaging to detect
      nigrostriatal cell loss in patients with Parkinson's disease or clinically
      uncertain parkinsonism: a systematic review.
AB  - In specialized movement disorder centers, Parkinson's disease (PD) is wrongly
      diagnosed in 6 to 25% of cases. To improve the accuracy of the clinical
      diagnosis, it is necessary to have a reliable and practical reference standard.
      Dopamine transporter single-photon emission computed tomography (DAT SPECT)
      imaging might have the potential (high diagnostic accuracy and practical to use)
      to act as reference standard in detecting nigrostriatal cell loss in patients
      with (early stage) parkinsonism. We performed a systematic review to evaluate if
      DAT SPECT imaging can be used as such. Relevant studies were searched in the
      MEDLINE and EMBASE databases. Studies were selected when they met the following
      criteria: (1) all patients were adults with a clinical diagnosis of PD or
      clinically uncertain parkinsonism and (2) the study reported original data. In
      addition, studies needed to fulfill one of the two following criteria: (1)
      patients underwent at least one DAT SPECT and had a neuropathological confirmed
      diagnosis and (2) patients underwent at least two DAT SPECT scans, performed at
      least 2 years apart. The search identified 1,649 articles. Eight studies
      fulfilled our selection criteria and were included in this review. There was only
      one study including patients with diagnostic uncertainty. Sensitivity and
      specificity of DAT SPECT imaging to detect nigrostriatal cell loss were 98%. The
      other studies included patients with a diagnosis of PD in whom there was no
      uncertainty. In these studies, sensitivity was 100%. Our systematic review
      indicates that DAT SPECT imaging seems to be accurate to detect nigrostriatal
      cell loss in patients with parkinsonism. 

PMID- 25853019
TI  - [(18)F]FDG-6-P as a novel in vivo tool for imaging staphylococcal infections.
AB  - BACKGROUND: Management of infection is a major clinical problem. Staphylococcus
      aureus is a Gram-positive bacterium which colonises approximately one third of
      the adult human population. Staphylococcal infections can be life-threatening and
      are frequently complicated by multi-antibiotic resistant strains including
      methicillin-resistant S. aureus (MRSA). Fluorodeoxyglucose ([(18)F]FDG) imaging
      has been used to identify infection sites; however, it is unable to distinguish
      between sterile inflammation and bacterial load. We have modified [(18)F]FDG by
      phosphorylation, producing [(18)F]FDG-6-P to facilitate specific uptake and
      accumulation by S. aureus through hexose phosphate transporters, which are not
      present in mammalian cell membranes. This approach leads to the specific uptake
      of the radiopharmaceutical into the bacteria and not the sites of sterile
      inflammation. METHODS: [(18)F]FDG-6-P was synthesised from [(18)F]FDG. Yield,
      purity and stability were confirmed by RP-HPLC and iTLC. The specificity of
      [(18)F]FDG-6-P for the bacterial universal hexose phosphate transporter (UHPT)
      was confirmed with S. aureus and mammalian cell assays in vitro. Whole body
      biodistribution and accumulation of [(18)F]FDG-6-P at the sites of bioluminescent
      staphylococcal infection were established in a murine foreign body infection
      model. RESULTS: In vitro validation assays demonstrated that [(18)F]FDG-6-P was
      stable and specifically transported into S. aureus but not mammalian cells.
      [(18)F]FDG-6-P was elevated at the sites of S. aureus infection in vivo compared
      to uninfected controls; however, the increase in signal was not significant and
      unexpectedly, the whole-body biodistribution of [(18)F]FDG-6-P was similar to
      that of [(18)F]FDG. CONCLUSIONS: Despite conclusive in vitro validation,
      [(18)F]FDG-6-P did not behave as predicted in vivo. However at the site of known
      infection, [(18)F]FDG-6-P levels were elevated compared with uninfected controls,
      providing a higher signal-to-noise ratio. The bacterial UHPT can transport hexose
      phosphates other than glucose, and therefore alternative sugars may show
      differential biodistribution and provide a means for specific bacterial
      detection.

PMID- 25853020
TI  - A comparative PET imaging study with the reversible and irreversible EGFR
      tyrosine kinase inhibitors [(11)C]erlotinib and [(18)F]afatinib in lung cancer
      bearing mice.
AB  - BACKGROUND: Tyrosine kinase inhibitors (TKIs) have experienced a tremendous boost
      in the last decade, where more than 15 small molecule TKIs have been approved by
      the FDA. Unfortunately, despite their promising clinical successes, a large
      portion of patients remain unresponsive to these targeted drugs. For non-small
      cell lung cancer (NSCLC), the effectiveness of TKIs is dependent on the
      mutational status of epidermal growth factor receptor (EGFR). The exon 19
      deletion as well as the L858R point mutation lead to excellent sensitivity to
      TKIs such as erlotinib and gefitinib; however, despite initial good response,
      most patients invariably develop resistance against these first-generation
      reversible TKIs, e.g., via T790M point mutation. Second-generation TKIs that
      irreversibly bind to EGFR wild-type and mutant isoforms have therefore been
      developed and one of these candidates, afatinib, has now reached the market.
      Whether irreversible TKIs differ from reversible TKIs in their in vivo tumor
      targeting properties is, however, not known and is the subject of the present
      study. METHODS: Erlotinib was labeled with carbon-11 and afatinib with fluorine
      18 without modifying the structure of these compounds. A preclinical positron
      emission tomography (PET) study was performed in mice bearing NSCLC xenografts
      with a representative panel of mutations: an EGFR-WT xenograft cell line (A549),
      an acquired treatment-resistant L858R/T790M mutant (H1975), and a treatment
      sensitive exon 19 deleted mutant (HCC827). PET imaging was performed in these
      xenografts with both tracers. Additionally, the effect of drug efflux transporter
      permeability glycoprotein (P-gp) on the tumor uptake of tracers was explored by
      therapeutic blocking with tariquidar. RESULTS: Both tracers only demonstrated
      selective tumor uptake in the HCC827 xenograft line (tumor-to-background ratio,
      [(11)C]erlotinib 1.9 +/- 0.5 and [(18)F]afatinib 2.3 +/- 0.4), thereby showing
      the ability to distinguish sensitizing mutations in vivo. No major differences
      were observed in the kinetics of the reversible and the irreversible tracers in
      each of the xenograft models. Under P-gp blocking conditions, no significant
      changes in tumor-to-background ratio were observed; however, [(18)F]afatinib
      demonstrated better tumor retention in all xenograft models. CONCLUSIONS: TKI-PET
      provides a method to image sensitizing mutations and can be a valuable tool to
      compare the distinguished targeting properties of TKIs in vivo.

PMID- 25853021
TI  - Evaluation of elastix-based propagated align algorithm for VOI- and voxel-based
      analysis of longitudinal (18)F-FDG PET/CT data from patients with non-small cell
      lung cancer (NSCLC).
AB  - BACKGROUND: Deformable image registration allows volume of interest (VOI)- and
      voxel-based analysis of longitudinal changes in fluorodeoxyglucose (FDG) tumor
      uptake in patients with non-small cell lung cancer (NSCLC). This study evaluates
      the performance of the elastix toolbox deformable image registration algorithm
      for VOI and voxel-wise assessment of longitudinal variations in FDG tumor uptake
      in NSCLC patients. METHODS: Evaluation of the elastix toolbox was performed using
      (18)F-FDG PET/CT at baseline and after 2 cycles of therapy (follow-up) data in
      advanced NSCLC patients. The elastix toolbox, an integrated part of the IMALYTICS
      workstation, was used to apply a CT-based non-linear image registration of follow
      up PET/CT data using the baseline PET/CT data as reference. Lesion statistics
      were compared to assess the impact on therapy response assessment. Next, CT-based
      deformable image registration was performed anew on the deformed follow-up PET/CT
      data using the original follow-up PET/CT data as reference, yielding a realigned
      follow-up PET dataset. Performance was evaluated by determining the correlation
      coefficient between original and realigned follow-up PET datasets. The intra- and
      extra-thoracic tumors were automatically delineated on the original PET using a
      41% of maximum standardized uptake value (SUVmax) adaptive threshold. Equivalence
      between reference and realigned images was tested (determining 95% range of the
      difference) and estimating the percentage of voxel values that fell within that
      range. RESULTS: Thirty-nine patients with 191 tumor lesions were included. In
      37/39 and 12/39 patients, respectively, thoracic and non-thoracic lesions were
      evaluable for response assessment. Using the EORTC/SUVmax-based criteria, 5/37
      patients had a discordant response of thoracic, and 2/12 a discordant response of
      non-thoracic lesions between the reference and the realigned image. FDG uptake
      values of corresponding tumor voxels in the original and realigned reference PET
      correlated well (R (2)=0.98). Using equivalence testing, 94% of all the voxel
      values fell within the 95% range of the difference between original and realigned
      reference PET. CONCLUSIONS: The elastix toolbox impacts lesion statistics and
      therefore therapy response assessment in a clinically significant way. The
      elastix toolbox is therefore not applicable in its current form and/or standard
      settings for PET response evaluation. Further optimization and validation of this
      technique is necessary prior to clinical implementation.

PMID- 25853022
TI  - Optimisation of quantitative lung SPECT applied to mild COPD: a software phantom
      simulation study.
AB  - BACKGROUND: The amount of inhomogeneities in a (99m)Tc Technegas single-photon
      emission computed tomography (SPECT) lung image, caused by reduced ventilation in
      lung regions affected by chronic obstructive pulmonary disease (COPD), is
      correlated to disease advancement. A quantitative analysis method, the CVT
      method, measuring these inhomogeneities was proposed in earlier work. To detect
      mild COPD, which is a difficult task, optimised parameter values are needed.
      METHODS: In this work, the CVT method was optimised with respect to the parameter
      values of acquisition, reconstruction and analysis. The ordered subset
      expectation maximisation (OSEM) algorithm was used for reconstructing the lung
      SPECT images. As a first step towards clinical application of the CVT method in
      detecting mild COPD, this study was based on simulated SPECT images of an
      advanced anthropomorphic lung software phantom including respiratory and cardiac
      motion, where the mild COPD lung had an overall ventilation reduction of 5%.
      RESULTS: The best separation between healthy and mild COPD lung images as
      determined using the CVT measure of ventilation inhomogeneity and 125 MBq (99m)Tc
      was obtained using a low-energy high-resolution collimator (LEHR) and a power 6
      Butterworth post-filter with a cutoff frequency of 0.6 to 0.7 cm(-1). Sixty-four
      reconstruction updates and a small kernel size should be used when the whole lung
      is analysed, and for the reduced lung a greater number of updates and a larger
      kernel size are needed. CONCLUSIONS: A LEHR collimator and 125 (99m)Tc MBq
      together with an optimal combination of cutoff frequency, number of updates and
      kernel size, gave the best result. Suboptimal selections of either cutoff
      frequency, number of updates and kernel size will reduce the imaging system's
      ability to detect mild COPD in the lung phantom.

PMID- 25853023
TI  - Fluorescence-guided development of a tricistronic vector encoding bimodal optical
      and nuclear genetic reporters for in vivo cellular imaging.
AB  - BACKGROUND: In vivo imaging using genetic reporters is a central supporting tool
      in the development of cell and gene therapies affording us the ability to
      selectively track the therapeutic indefinitely. Previous studies have
      demonstrated the utility of the human norepinephrine transporter (hNET) as a
      positron emission tomography/single photon emission computed tomography
      (PET/SPECT) genetic reporter for in vivo cellular imaging. Here, our aim was to
      extend on this work and construct a tricistronic vector with dual optical
      (firefly luciferase) and nuclear (hNET) in vivo imaging and ex vivo histochemical
      capabilities. Guiding this development, we describe how a fluorescent substrate
      for hNET, 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP(+)), can be used to
      optimise vector design and serve as an in vitro functional screen. METHODS:
      Vectors were designed to co-express a bright red-shifted firefly luciferase
      (FLuc), hNET and a small marker gene RQR8. Genes were co-expressed using 2A
      peptide linkage, and vectors were transduced into a T cell line, SupT1. Two
      vectors were constructed with different gene orientations; FLuc.2A.RQR8.2A.hNET
      and hNET.2A.FLuc.2A.RQR8. hNET function was assessed using ASP(+)-guided flow
      cytometry. In vivo cellular conspicuity was confirmed using sequential
      bioluminescence imaging (BLI) and SPECT imaging of transduced SupT1 cells
      injected into the flanks of mice. RESULTS: SupT1/FLuc.2A.RQR8.2A.hNET cells
      resulted in >4-fold higher ASP(+) uptake compared to SupT1/hNET.2A.FLuc.2A.RQR8,
      suggesting that 2A orientation effected hNET function. SupT1/FLuc.2A.RQR8.2A.hNET
      cells were readily visualised with both BLI and SPECT, demonstrating high signal
      to noise at 24 h post (123)I-meta-iodobenzylguanidine (MIBG) administration.
      CONCLUSIONS: In this study, a pre-clinical tricistronic vector with flow
      cytometry, BLI, SPECT and histochemical capabilities was constructed, which can
      be widely applied in cell tracking studies supporting the development of cell
      therapies. The study further demonstrates that hNET function in engineered cells
      can be assessed using ASP(+)-guided flow cytometry in place of costly
      radiosubstrate methodologies. This fluorogenic approach is unique to the hNET
      PET/SPECT reporter and may prove valuable when screening large numbers of cell
      lines or vector/mutant constructs.

PMID- 25853024
TI  - Reconstruction of productivity signal and deep-water conditions in Moroccan
      Atlantic margin (~35 degrees N) from the last glacial to the Holocene.
AB  - In order to assess the changes in sea-surface hydrology and productivity signal
      from the last glacial to the Holocene; a set of isotopic, geochemical and
      microgranulometric proxies was used for this study. Former studies revealed that
      the reconstruction of paleoproductivity from ocean sediment gives different
      results depending the measurement used. The comparison between our productivity
      proxies (total organic carbon, carbonate and planktonic delta(13)C) as well as
      previous results in nearby location indicates that the planktonic delta(13)C
      responds better to marine productivity changes and represents therefore a
      suitable proxy for paleoproductivity reconstruction in our studied area. The
      productivity signal reveals two main enrichments during the Young Dryas (YD) and
      the Heinrich Event 1 (HE 1) and correlates perfectly with upwelling activity
      mentioned by an increasing trend of aeolian proxies. In addition, our results
      show that biogenic components in the sediment have a marine origin and the
      proportion of organic matter preserved depends on the total sediment accumulation
      rate. 

PMID- 25853025
TI  - Case study to assess the safety of irreversible electroporation near the heart.
AB  - INTRODUCTION: Irreversible electroporation (IRE) is a promising technique for the
      focal treatment of soft tissue tumors. Even though the local application of an
      excessive electric field is a potential cause of cardiac arrhythmias, initial
      clinical studies have shown that IRE is generally safe when cardiac gating is
      employed. CASE DESCRIPTION: In this case report, we observed an episode of
      ventricular extrasystoles without hemodynamic changes during which time the
      synchronization device failed to operate properly, with pulses delivered not in
      the absolute refractory period but in the relative refractory period. DISCUSSION
      AND EVALUATION: At present, persons performing IRE must keep in mind that there
      is a small but real risk of synchronization failure even when a cardiac
      synchronization device is used. CONCLUSION: It is advisable to err on the side of
      caution when treating lesions near the heart.

PMID- 25853026
TI  - Iron, manganese, cadmium, chromium, zinc and arsenic groundwater contents of
      Agbor and Owa communities of Nigeria.
AB  - Iron, manganese, zinc, cadmium, and chromium heavy metals and arsenic contents of
      groundwater in area and surrounding environment, of Ika land in the Delta state,
      Nigeria was studied. Groundwater without any treatment is the predominant source
      of drinking water by inhabitants of these communities. However, the quality of
      this water source is not immediately known, raising questions of its safety.
      Results of a regional composite of groundwater obtained, shows high iron (27%)
      and zinc (36%) contents in Boji-Boji Agbor area, manganese (31%) was highest in
      Boji-Boji Owa. Alihame recorded the lowest value of zinc (8%), while manganese
      was lowest in Agbor Obi area (12%). Arsenic, cadmium, and chromium were below
      detection limit in all the sample sites. Correlational matrix analysis revealed
      no significant relationships between metal types studied. Analyses of chronic
      daily dose intake (CDI), and hazard index were all very low. A hazard index of
      0.01 was obtained. One-way ANOVA show significant statistical difference in the
      mean concentrations of the heavy metals for the different sample sites, which
      indicate that different sites contribute differently to the mean concentrations
      of the groundwater in the study area. Four conclusions are drawn from this study.
      Indications are that the heavy metals present in the Nigerian aquifer are very
      much below the maximum concentration levels and guideline values of national and
      WHO standards. Secondly, there is a heavier load of these metals in the city
      centre than in the suburbs; with Boji-Boji area Agbor/Owa urban areas accounting
      for 27 and 20 percent of load respectively. Thirdly, the below detection limit
      results for some of the metal ions and the very low concentrations of those
      detected are pointers to the absence of industrial activities and mining.
      Finally, the groundwater in the study area is considered to be generally safe
      with respect to the contaminants studied and results posted for the composite
      samples. Inhabitants are therefore under no illusion of immediate or remote
      health challenges with regards to the heavy metals analyzed. More individual
      sampling, however, is recommended. 

PMID- 25853027
TI  - Selective pruning in pineapple plants as means to reduce heterogeneity in fruit
      quality.
AB  - Heterogeneity in fruit quality (size and taste) is a major problem in pineapple
      production chains. The possibilities were investigated of reducing the
      heterogeneity in pineapple in the field by pruning slips on selected plants, in
      order to promote the fruit growth on these plants. Slips are side shoots that
      develop just below the pineapple fruit during fruit development. Two on-farm
      experiments were carried out in commercial fields in Benin with a cultivar
      locally known as Sugarloaf, to determine (a) the effect of slip pruning on fruit
      quality; (b) whether the effect of slip pruning depends on the pruning time; and
      (c) whether slip pruning from the plants with the smallest infructescences
      results in more uniformity in fruit quality. A split-plot design was used with
      pruning time (2 or 3 months after inflorescence emergence) as main factor and
      fraction of pruned plants (no plants pruned (control); pruning on the one-third
      plants with the smallest infructescences; pruning on the two-thirds plants with
      the smallest infructescences; pruning on all plants) as sub-factor. Fruit quality
      characteristics measured at harvest were the fruit (infructescence + crown)
      weight and length, the infructescence weight and length, the crown weight and
      length, the ratio crown length: infructescence length, the total soluble solids,
      the juice pH and the flesh translucency. Results indicated that pruning of slips
      of any fraction of the plants at 2 or 3 months after inflorescence emergence did
      not lead to a consistent improvement in quality or uniformity. Consequently it is
      not recommended to farmers in Benin to prune the slips. 

PMID- 25853028
TI  - A population-based analysis of outcomes for small cell carcinoma of the breast by
      tumor stage and the use of radiation therapy.
AB  - PURPOSE: Primary small cell carcinomas of the breast (SCCB) are rare tumors with
      limited data on outcomes and treatment strategies. Using a population based
      approach, we aimed to study outcomes of SCCB and determine whether the use of
      radiation therapy is associated with better survival among patients with SCCB.
      METHODS: Using the Surveillance, Epidemiology and End Results (SEER) registry, we
      identified patients with SCCB between1973 and 2010. We examined the stage
      specific survival of these patients and compared it to the stage specific
      survival of small cell lung cancer (SCLC) from the SEER database over the same
      accrual period. We further analyzed the impact of radiation therapy on overall
      survival for SCCB patients using a univariate and multivariate approach. RESULTS:
      A total of 199 patients with primary SCCB with staging were identified during the
      study period. Eighty-four patients (42%) had localized disease, 77 (39%) had
      regional disease and 38 (19%) had distant disease. For comparison, 81,933
      patients with SCLC were identified. Outcomes were superior for patients with SCCB
      with localized (150 vs. 16 months, p < 0.01) and regional disease (56 vs. 13
      months, p < 0.01), but not distant disease (7 vs. 7 months, p = 0.43). Use of
      radiation therapy was not associated with a significant difference in OS for
      patients with either localized (202 vs. 147 months, p = 0.48) or regional (52 vs.
      75 months, p = 0.650) disease. CONCLUSIONS: SCCB has a more favorable prognosis
      by stage for localized and regional disease than SCLC. Adjuvant radiation is not
      associated with an improvement in survival for patients with localized or
      regional SCCB in this dataset.

PMID- 25853029
TI  - Finite element/percolation theory modelling of the micromechanical behavior of
      clayey soils.
AB  - A hybrid model for soils, which combines percolation theory and finite element
      method is presented. The internal soil structure is modelled via the finite
      element method, and percolation networks are used for analyzing its mechanical
      behaviour. Through a microscopic characterization of elastic properties of soil
      grains, the model is generated. The effective percolation threshold obtained is
      lower than that of the network geometric percolation. The effective mechanical
      properties predicted are successfully compared to published experimental results.

PMID- 25853031
TI  - Within field spatial variation in methane emissions from lowland rice in Myanmar.
AB  - An assessment of within field spatial variations in grain yield and methane (CH4)
      emission was conducted in lowland rice fields of Myanmar. Two successive rice
      fields (1(st) field and 2(nd) field) were divided into fertilized and non
      fertilized parts and CH4 measurements were conducted at the inlet, middle and
      outlet positions of each field. The results showed that CH4 emissions at non
      fertilized parts were higher than those at fertilized part in both rice fields.
      The average CH4 emissions ranged from 8.7 to 26.6 mg m(-2) h(-1) in all positions
      in both rice fields. The spatial variation in CH4 emission among the positions
      was high in both rice fields with the highest emissions in the outlet of the
      1(st) field and the inlet of the 2(nd) field. The CH4 emissions at these two
      positions showed 2 - 2.5 times higher than those at other positions in both rice
      fields. Stepwise regression analysis indicates that soil total carbon content is
      the primary factor for CH4 emission. The average CH4 emissions during rice
      growing season were 13.5 mg m(-2) h(-1) for the 1(st) field and 15.7 mg m(-2) h(
      1) for the 2(nd) field. Spearman rank order correlation analysis showed that CH4
      emission was significantly and positively correlated with soil temperature,
      surface water depth and negatively correlated with soil redox potential. The
      result indicated that high within field spatial variation in CH4 emissions
      required different site specific management practices to mitigate CH4 emissions
      in lowland paddy rice soil. 

PMID- 25853030
TI  - Effects of six months of Yoga on inflammatory serum markers prognostic of
      recurrence risk in breast cancer survivors.
AB  - Yoga-based exercise has proven to be beneficial for practitioners, including
      cancer survivors. This study reports on the effect on inflammatory biological
      markers for 20 breast cancer survivors who participated in a six-month yoga-based
      (YE) exercise program. Results are compared to a comprehensive exercise (CE)
      program group and a comparison (C) exercise group who chose their own exercises.
      "Pre" and "post" assessments included measures of anthropometrics,
      cardiorespiratory capacity, and inflammatory markers interleukin 6 (IL-6),
      interleukin 8 (IL-8), tumor necrosis factor alpha (TNFalpha) and C-reactive
      protein (CRP). Descriptive statistics, effect size (d), and dependent sample 't'
      tests for all outcome measures were calculated for the YE group. Significant
      improvements were seen in decreased % body fat, (-3.00%, d = -0.44, p = <.001)
      but not in cardiorespiratory capacity or in inflammatory serum markers. To
      compare YE outcomes with the other two groups, a one-way analysis of co-variance
      (ANCOVA) was used, controlling for age, BMI, cardiorespiratory capacity and serum
      marker baseline values. We found no differences between groups. Moreover, we did
      not see significant changes in any inflammatory marker for any group. Our results
      support the effectiveness of yoga-based exercise modified for breast cancer
      survivors for improving body composition. Larger studies are needed to determine
      if there are significant changes in inflammatory serum markers as a result of
      specific exercise modalities. 

PMID- 25853033
TI  - An emergentist vs a linear approach to social change processes: a gender look in
      contemporary India between modernity and Hindu tradition.
AB  - Using Census of India data from 1901 to 2011 and national and international
      reports on women's condition in India, beginning with sex ratio trends according
      to regional distribution up to female infanticides and sex-selective abortions
      and dowry deaths, this study examines the sociological aspects of the gender
      imbalance in modern contemporary India. Gender inequality persistence in India
      proves that new values and structures do not necessarily lead to the
      disappearance of older forms, but they can co-exist with mutual adaptations and
      reinforcements. Data analysis suggests that these unexpected combinations are not
      comprehensible in light of a linear concept of social change which is founded, in
      turn, on a concept of social systems as linear interaction systems that relate to
      environmental perturbations according to proportional cause and effect
      relationships. From this perspective, in fact, behavioral attitudes and
      interaction relationships should be less and less proportionally regulated by
      traditional values and practices as exposure to modernizing influences increases.
      And progressive decreases should be found in rates of social indicators of gender
      inequality like dowry deaths (the inverse should be found in sex ratio trends).
      However, data does not confirm these trends. This finding leads to emphasize a
      new theoretical and methodological approach toward social systems study, namely
      the conception of social systems as complex adaptive systems and the
      consequential emergentist, nonlinear conception of social change processes.
      Within the framework of emergentist theory of social change is it possible to
      understand the lasting strength of the patriarchal tradition and its problematic
      consequences in the modern contemporary India. 

PMID- 25853032
TI  - Expression and functional validation of heat-labile enterotoxin B (LTB) and
      cholera toxin B (CTB) subunits in transgenic rice (Oryza sativa).
AB  - We expressed the heat-labile enterotoxin B (LTB) subunit from enterotoxigenic
      Escherichia coli and the cholera toxin B (CTB) subunit from Vibrio cholerae under
      the control of the rice (Oryza sativa) globulin (Glb) promoter. Binding of
      recombinant LTB and CTB proteins was confirmed based on GM1-ganglioside binding
      enzyme-linked immunosorbent assays (GM1-ELISA). Real-time PCR of three
      generations (T3, T4, and T5) in homozygous lines (LCI-11) showed single copies of
      LTB, CTB, bar and Tnos. LTB and CTB proteins in rice transgenic lines were
      detected by Western blot analysis. Immunogenicity trials of rice-derived CTB and
      LTB antigens were evaluated through oral and intraperitoneal administration in
      mice, respectively. The results revealed that LTB- and CTB-specific IgG levels
      were enhanced in the sera of intraperitoneally immunized mice. Similarly, the
      toxin-neutralizing activity of CTB and LTB in serum of orally immunized mice was
      associated with elevated levels of both IgG and IgA. The results of the present
      study suggest that the combined expression of CTB and LTB proteins can be
      utilized to produce vaccines against enterotoxigenic strains of Escherichia coli
      and Vibrio cholera, for the prevention of diarrhea. 

PMID- 25853034
TI  - In-home occupational therapy for a patient with stage IV lung cancer: changes in
      quality of life and analysis of causes.
AB  - INTRODUCTION: We tracked and analyzed the changes in the quality of life (QOL) of
      a stage 4 lung cancer patient receiving occupational therapy at home. CASE
      DESCRIPTION: In a longitudinal study consisting of 4 evaluations over 9 months, a
      66-year-old female with lung cancer was assessed using the Philadelphia Geriatric
      Center (PGC) Morale Scale and the 100-Point Satisfaction Scale. The QOL scores
      over time and factors influencing changes in these scores were analyzed.
      DISCUSSION AND EVALUATION: A histogram of QOL scores demonstrated a rapid
      increase followed by a mild decrease and then stable level. Interviews revealed
      the patient's response to knowing her life expectancy, meeting a qualified
      occupational therapist, increasing her leisure activity, changing her family
      relationships and facing the prospect of death. We also confirmed that
      occupational therapy, such as writing letters or keeping a diary, reminded her of
      her late parents, hometown and childhood and helped her accept death.
      CONCLUSIONS: For a terminal lung cancer patient, meeting an occupational
      therapist to discuss fear or self-loathing improved QOL. Further, an active
      lifestyle played an important role in helping the patient accept death and lead a
      peaceful and stable life.

PMID- 25853035
TI  - Study of circulating IgG antibodies to peptide antigens derived from BIRC5 and
      MYC in cervical cancer.
AB  - The present study was undertaken to detect circulating IgG antibodies to peptide
      antigens derived from baculoviral IAP repeat-containing protein 5 isoform 2
      (BIRC5) and myc proto-oncogene protein (MYC) in cervical cancer. A total of 107
      female patients with cervical cancer of stages I and II, and 130 healthy female
      subjects were recruited for analysis of circulating IgG antibodies to BIRC5 and
      MYC. Student's t-test showed significant differences in circulating levels of
      anti-BIRC5 IgG (t = -4.27, df = 235, P < 0.0001) and anti-MYC IgG (t = 3.51, df =
      232, P = 0.0005) between the patient group and the control group. Receiver
      operating characteristic (ROC) analysis showed an area under the ROC curve (AUC)
      of 0.67 with sensitivity of 23.4% against specificity of 90% for the anti-BIRC5
      IgG assay and an AUC of 0.66 with sensitivity of 9.4% against specificity of
      90.6% for the anti-MYC IgG assay. Analysis of quality control samples gave an
      inter-assay deviation of 8.9% in the anti-BIRC5 IgG assay and 9.0% in the anti
      MYC IgG assay. This work suggests that anti-BIRC5 IgG could serve as a biomarker
      for early diagnosis of cervical cancer although a panel of such tumor-associated
      antigens is needed to develop a highly sensitive test. 

PMID- 25853036
TI  - Design and evaluation of a peptide-based immunotoxin for breast cancer
      therapeutics.
AB  - Immunotoxins are chimeric proteins comprising a specific cellular targeting
      domain linked to a cytotoxic factor. Here we describe the design and use of a
      novel, peptide-based immunotoxin that can initiate selective cytotoxicity on
      ErbB2-positive cells. ErbB2 is a receptor tyrosine kinase that is overexpressed
      in the tumor cells of approximately 30% of breast cancer patients. Immunotoxin
      candidates were designed to incorporate a targeting ligand with affinity for
      ErbB2 along with a membrane lysin-based toxin domain. One particular peptide
      candidate, NL1.1-PSA, demonstrated selective cytotoxicity towards ErbB2
      overexpressing cell lines. We utilized a bioengineering strategy to show that
      recombinant NL1.1-PSA immunotoxin expression by Escherichia coli also conferred
      selective cytotoxicity towards ErbB2-overexpressing cells. Our findings hold
      significant promise for the use of effective immunotoxins in cancer therapeutics.

PMID- 25853039
TI  - Nano-science and dentistry.

PMID- 25853037
TI  - Biochemical and spectroscopic properties of Brucella microti glutamate
      decarboxylase, a key component of the glutamate-dependent acid resistance system.
AB  - In orally acquired bacteria, the ability to counteract extreme acid stress (pH ?
      2.5) ensures survival during transit through the animal host stomach. In several
      neutralophilic bacteria, the glutamate-dependent acid resistance system (GDAR) is
      the most efficient molecular system in conferring protection from acid stress. In
      Escherichia coli its structural components are either of the two glutamate
      decarboxylase isoforms (GadA, GadB) and the antiporter, GadC, which imports
      glutamate and exports gamma-aminobutyrate, the decarboxylation product. The
      system works by consuming protons intracellularly, as part of the decarboxylation
      reaction, and exporting positive charges via the antiporter. Herein, biochemical
      and spectroscopic properties of GadB from Brucella microti (BmGadB), a Brucella
      species which possesses GDAR, are described. B. microti belongs to a group of
      lately described and atypical brucellae that possess functional gadB and gadC
      genes, unlike the most well-known "classical" Brucella species, which include
      important human pathogens. BmGadB is hexameric at acidic pH. The pH-dependent
      spectroscopic properties and activity profile, combined with in silico sequence
      comparison with E. coli GadB (EcGadB), suggest that BmGadB has the necessary
      structural requirements for the binding of activating chloride ions at acidic pH
      and for the closure of its active site at neutral pH. On the contrary, cellular
      localization analysis, corroborated by sequence inspection, suggests that BmGadB
      does not undergo membrane recruitment at acidic pH, which was observed in EcGadB.
      The comparison of GadB from evolutionary distant microorganisms suggests that for
      this enzyme to be functional in GDAR some structural features must be preserved. 

PMID- 25853038
TI  - Impaired respiratory function in MELAS-induced pluripotent stem cells with high
      heteroplasmy levels.
AB  - Mitochondrial diseases are heterogeneous disorders, caused by mitochondrial
      dysfunction. Mitochondria are not regulated solely by nuclear genomic DNA but by
      mitochondrial DNA. It is difficult to develop effective therapies for
      mitochondrial disease because of the lack of mitochondrial disease models.
      Mitochondrial myopathy, encephalomyopathy, lactic acidosis, and stroke-like
      episodes (MELAS) is one of the major mitochondrial diseases. The aim of this
      study was to generate MELAS-specific induced pluripotent stem cells (iPSCs) and
      to demonstrate that MELAS-iPSCs can be models for mitochondrial disease. We
      successfully established iPSCs from the primary MELAS-fibroblasts carrying 77.7%
      of m.3243A>G heteroplasmy. MELAS-iPSC lines ranged from 3.6% to 99.4% of
      m.3243A>G heteroplasmy levels. The enzymatic activities of mitochondrial
      respiratory complexes indicated that MELAS-iPSC-derived fibroblasts with high
      heteroplasmy levels showed a deficiency of complex I activity but MELAS-iPSC
      derived fibroblasts with low heteroplasmy levels showed normal complex I
      activity. Our data indicate that MELAS-iPSCs can be models for MELAS but we
      should carefully select MELAS-iPSCs with appropriate heteroplasmy levels and
      respiratory functions for mitochondrial disease modeling. 

PMID- 25853040
TI  - Glucometric assessment of gingival crevicular blood in diabetic and non-diabetic
      patients: A randomized clinical trial.
AB  - BACKGROUND: Diabetes mellitus is one of the most incessant metabolic afflictions
      with high prevalence rate in Indians. Diagnosis of diabetics in the initial stage
      helps to prevent its long term complications that are responsible for high
      morbidity and mortality. The aim of the present study was to assess whether
      glucometric analysis using Gingival Crevicular Blood (GCB) can be used for
      screening of diabetic patients in dental chair. MATERIALS AND METHODS: Present
      study was a double blinded randomized controlled trial. A total of 50 patients,
      25 diabetic and 25 non-diabetic with chronic periodontitis were enrolled in the
      study. Blood oozing from the gingival crevices after periodontal pocket probing
      of anterior teeth and Finger Prick Blood (FPB) was taken and analysed by
      glucometer. RESULT: Mean +/- S.D was 195.84 +/- 27.19 and 138.78 +/- 29.95 for
      GCB and FPB respectively in diabetic group. For non-diabetic group Mean +/- S.D
      was 103.84 +/- 12.56 and 84.36 +/- 10.36 respectively for GCB and FPB. A Karl
      Pearson correlation coefficient value of r = +0.735 for diabetic and r = +0.802
      for non-diabetic group comparing GCB and FPB. CONCLUSION: GCB cannot be used for
      screening blood glucose during periodontal examination.

PMID- 25853041
TI  - Antibacterial activity of clove, gall nut methanolic and ethanolic extracts on
      Streptococcus mutans PTCC 1683 and Streptococcus salivarius PTCC 1448.
AB  - INTRODUCTION: Antimicrobial compounds from herbal sources have good therapeutic
      potential. In this study, the antibacterial effects of clove and gall nut,
      methanolic and ethanolic extractions, were evaluated for their effect on
      Streptococcus mutans PTCC 1683 and Streptococcus salivarius PTCC 1448, as both
      the two cause oral diseases. METHOD: The clove and gall nut methanolic and
      ethanolic extracts were prepared and antibacterial activity was evaluated for S.
      mutans and S. salivarius in the base of inhibition zone diameter using agar
      diffusion method. In this part minimum inhibitory concentration (MIC) and minimal
      bactericidal concentration (MBC) were assessed. RESULTS: These extracts showed
      effective antibacterial activity on bacteria. Antibacterial activity of
      Methanolic extract of clove was more than that of ethanolic extract, and
      ethanolic extracts of gall nut had antibacterial activity more than that of
      methanolic extracts. MIC and MBC results for clove methanolic extract were 1.5
      mg/ml and 3 mg/ml for S. mutans and 6.25 mg/ml and 12.5 mg/ml for S. salivarius,
      respectively. These results for clove ethanolic extracts were 12.5 mg/ml and 25
      mg/ml for S. mutans and 25 mg/ml and 50 mg/ml for S. salivarius, respectively.
      MIC and MBC results for gall nut methanolic extract were 25 mg/ml and 50 mg/ml
      for S. mutans and 12.5 mg/ml and 25 mg/ml for S. salivarius, respectively. These
      results for gall nut ethanolic extracts were 3.1 mg/ml and 6.2 mg/ml for S.
      mutans and 25 mg/ml and 50 mg/ml for S. salivarius, respectively. DISCUSSION: The
      results showed effective antibacterial activity using clove and gall nut
      methanolic extracts. If other properties such as tolerance of tissue can also be
      studied, these extracts can be used as a mouthwash.

PMID- 25853042
TI  - Comparative evaluation of natural antioxidants spirulina and aloe vera for the
      treatment of oral submucous fibrosis.
AB  - AIM: Oral submucous fibrosis (OSMF) is a high risk premalignant condition
      predominantly seen in the Indian subcontinent. The aim of the present study was
      to compare the efficacy of spirulina and aloe vera in the management of OSMF.
      MATERIAL AND METHODS: 42 subjects with clinico-pathologically diagnosed OSMF were
      included in the study and divided equally in 2 groups, Group A (spirulina group)
      and Group B (aloe vera group). Group A was administered 500 mg spirulina in 2
      divided doses for 3 months and Group B was given 5 mg aloe vera gel to be applied
      topically thrice daily for 3 months. Evaluation for different clinical parameters
      was done at regular intervals and data was analyzed using the Chi-square test. P
      value <0.05 was considered to be statistically significant. RESULTS: The patients
      in Group A showed significant clinical improvement in mouth opening and
      ulcers/erosions/vesicles (p < 0.05). However, there was no significant
      improvement in burning sensation (p = 0.06) and pain associated with the lesion
      (p = 0.04) among the 2 groups. CONCLUSION: Both the drugs showed improvement in
      the condition; however spirulina can bring about significant clinical
      improvements in the symptoms like mouth opening and ulcers/erosion/vesicles.
      Thus, spirulina appears to be more promising when compared to aloe vera for the
      treatment of OSMF.

PMID- 25853043
TI  - Prevalence and predictors of tobacco use among general public of Gorakhpur
      district, India.
AB  - OBJECTIVES: The present study was undertaken to determine the prevalence and
      demographic correlates of tobacco use in the adult population. METHOD: The sample
      selection was based on stratified random sampling technique selecting a total of
      1635 persons from different parts of Gorakhpur district of Uttar Pradesh, India.
      The demographic details of participants along with prevalence of tobacco use were
      recorded. RESULTS: The prevalence of tobacco use among the subpopulation studied
      was 31.1% for males and 6.1 for females. Both smoking and chewing tobacco were
      found to be associated with various demographic parameters. The rural population
      showed a higher prevalence of tobacco use among both males and females; the male
      smoking prevalence was higher in the urban population (23.0%) than its rural
      counterpart (18.1%). Also the prevalence of tobacco use was directly
      proportionate to age increasing upto the age of approximately 60 years, then
      declined. Stepwise Regression analysis showed gender as the strongest predictor
      for smoking followed by area of residence, education and age. Whereas education
      was the most significant predictors for chewing tobacco, followed by gender and
      age. CONCLUSION: The results of this study clearly indicate an association
      between tobacco prevalence and various demographic factors. To reduce the cancer
      burden, intervention measures to control tobacco use should specifically target
      those socio-demographic predictors of the subpopulation which are more
      susceptible to tobacco consumption.

PMID- 25853044
TI  - Pre-emptive effect of dexamethasone injection and consumption on post-operative
      swelling, pain, and trismus after third molar surgery. A prospective, double
      blind and randomized study.
AB  - AIM: To evaluate the preventative effect of intravenous 4 mg of dexamethasone and
      8 mg oral dexamethasone on post-operative pain, swelling and trismus after the
      surgical extraction of mandibular third molars. MATERIALS AND METHODS: A
      randomized clinical trial comprised of 200 patients (control group I intravenous
      and experimental group II orally) with impacted lower third molars, average age
      20.8 years with no local or systemic problems, with bilateral impacted lower
      third molars, were operated under local anesthesia. Group I was given 4 mg IV and
      group II was given 8 mg orally of dexamethasone 1 h before procedure. The choice
      of which side to operate first and the amount of concentration of medication to
      use was made randomly and double-blindly. Post-operative pain was evaluated using
      a visual analog scale (VAS) and the degree of swelling was evaluated through
      facial reference points' variation. The presence of trismus was analyzed through
      measurement of the interincisal distance (IID). These assessments were obtained
      before the operation and 24 h, 48 h and 7th POD. RESULTS: No significant
      difference was found in facial swelling and trismus between IV 4 mg injection and
      oral 8 mg consumption after lower third molar surgery (student t test P > 0.05).
      The visual analogue scale scores for pain assessment showed no significant
      difference between IV injection and oral route of dexamethasone (student t test P
      > 0.05). CONCLUSION: Patients can be administered 8 mg oral dexamethasone is as
      effective as 4 mg intra venous route without much difference in final outcome at
      any given point of time.

PMID- 25853045
TI  - The role of salivary caffeine clearance in the diagnosis of chronic liver
      disease.
AB  - BACKGROUND: Chronic liver diseases (CLD) are quite prevalent throughout the
      globe. Its early and correct diagnosis is always a concern among physicians,
      especially the residual liver function. For this various substrates like caffeine
      are being investigated in body fluids like serum and saliva. Saliva as a study
      sample has its own advantages due to its non invasiveness; it can be very useful
      study sample. METHODS: 30 Subjects with CLD and 15 healthy controls were
      administered 200 mg of caffeine. Subjects classified into severity groups (class
      A-mild-n = 9, B-moderate-n = 11, and C-severe-n = 10) based on "Child-pugh
      classification" of severity of liver disease. After 17 h of dietary caffeine
      restriction and before drug administration, 0 h salivary sample was taken. After
      the dose of caffeine, 4 and 16 h saliva sample was taken. Blood sample was taken
      from controls only at same time points. These samples were analyzed on semi
      automated analyzer using Enzyme Multiplied Immunoassay Technique (EMIT) by
      spectrophotometric method. Caffeine clearance values were calculated and results
      were statistically analyzed. RESULTS: Significant correlation was found between
      serum caffeine clearance and salivary caffeine clearance (SCC). Controls showed
      higher mean of SCC value of 1.6 +/- 0.2 ml/min/kg while SCC values of subjects
      were less, with mean of 0.5 +/- 0.2 ml/min/kg. Significant correlation was found
      between degree of hepatic dysfunction and SCC values. CONCLUSION: Saliva can be
      used for diagnosis of CLD and assessment of residual liver function in CLD as
      alternative to serum.

PMID- 25853046
TI  - Evaluation of effects of a preoperative 2-hour fast with glutamine and
      carbohydrate rich drink on insulin resistance in maxillofacial surgery.
AB  - INTRODUCTION: The aim of this prospective, randomized, single-blinded study was
      to compare the effects of preoperative fast for clear fluids on insulin
      resistance and hemodynamic stability on patient undergoing maxillofacial surgery.
      METHOD: In this study 20 patients undergoing maxillofacial surgery were
      randomized into four groups i.e. - group I patients with standard 08 h fasting
      before anesthesia, group-II patients were given 400 ml and 200 ml of water 08 h
      and 2 h respectively before anesthesia, group III patients were given 400 ml
      water with 50 gms of glucose and 40 gm of glutamine 08 h before anesthesia and
      200 ml water with 25 gms of glucose and 10 gm of glutamine 2 h before anesthesia,
      group IV patients were given 400 ml water with 50 gms of glucose 08 h before
      anesthesia and 200 ml water with 25 gms of glucose 2 h before anesthesia. Blood
      samples were collected pre-operatively and post-operatively. RESULTS: Overall
      results suggest that Post-operative insulin resistance was greater in control
      patients (2.0 [0.3]) compared with the other 3 groups (placebo = 1.8 [0.9]);
      glutamine = (1.8 [0.6]); carbohydrate = (1.9 [0.6]). DISCUSSION: This study shows
      that shortening of pre-operative fasting time for clear fluids until 2- h prior
      to anesthesia may induce a favorable environment for the post-operative course.
      In conclusion, Glutamine with carbohydrate drink can be used safely in surgical
      patients.

PMID- 25853047
TI  - Relationship of the lingual frenum to the mandibular central incisors.
AB  - CLINICAL IMPLICATION: The purpose of this study is to record the vertical
      distance between anterior attachment of lingual frenum and incisal edge of
      mandibular central incisors in dentulous subjects and then determine the mean
      vertical distance and to suggest guidelines for positioning of mandibular central
      incisors in complete dentures. METHOD: In this study, 150 dentulous subjects (75
      males and 75 females) were chosen based on predecided inclusion criteria. A
      mandibular cast was obtained from irreversible hydrocolloid impression in
      modified stock trays for each subject. All subjects were instructed to elevate
      the tongue while the impressions were made. The vertical distance between the
      anterior attachment of the lingual frenum and incisal edges of mandibular central
      incisors was measured on the casts and then the values were statistically
      analyzed. RESULT: The distance between anterior attachment of lingual frenum
      (AALF) mesioincisal edge of mandibular central incisor (CI) in male, female and
      total (male + female) subjects was measured. In males it ranged from 7.3 to 8.9
      mm with mean (+/-SD) 8.29 +/- 0.36 mm while in females it ranged from 7.1 to 9.0
      mm with mean (+/-SD) 8.21 +/- 0.38 mm. CONCLUSION: It is believed that the
      application of this anatomic relation can provide a reliable point for arranging
      and checking the position of the mandibular central incisors for complete
      dentures in patients with class I ridge relationship.

PMID- 25853048
TI  - Proteomics - The research frontier in periodontics.
AB  - Periodontitis is an inflammatory condition resulting from the interplay between
      the infectious agents and host factors. Various protein molecules play a vital
      role in the initiation, progression and severity of periodontal diseases. The
      study of proteins as biomarkers in periodontal diseases has been highlighted
      during the last few years. In periodontitis multiple bacteria derived (e.g.
      collagen degrading enzymes, elastase like enzymes etc) and host derived mediators
      (eg. PGE2, TNF, IL1, IL6, MMP's etc) expressed in the saliva and gingival
      crevicular fluid, can be utilized as diagnostic markers for the disease. Another
      significant development regarding human genes and proteins has been the discovery
      of potential new drugs for the treatment of periodontal diseases. Therefore the
      information of the proteins involved in the pathogenesis of periodontal diseases
      can be utilized for its diagnosis, prevention and treatment. 

PMID- 25853049
TI  - Sturge-Weber syndrome - A case report.
AB  - Sturge-Weber syndrome (SWS), also called as encephalotrigeminal angiomatosis is
      an uncommon congenital neurological disorder & frequent among the neurocutaneous
      syndromes specifically with vascular predominance. This disorder is characterized
      by facial capillary malformation & other neurological condition. The oral
      manifestations are gingival hemangiomatosis restricting to either side in upper
      and lower jaw, sometimes bilateral. We report a case of SWS with oral, ocular and
      neurological features. 

PMID- 25853050
TI  - Intestinal coccidiosis of anadromous and landlocked alewives, Alosa
      pseudoharengus, caused by Goussia ameliae n. sp. and G. alosii n. sp.
      (Apicomplexa: Eimeriidae).
AB  - Anadromous alewives, Alosa pseudoharengus, have experienced significant
      population level declines caused by factors including habitat destruction.
      Alewives occur in two different life histories, anadromous and landlocked forms.
      The landlocked alewife evolved from ancestral anadromous populations, resulting
      in an exclusively freshwater and phenotypically unique form. The occurrence of
      parasites in a host is linked to the environment, making alewives an ideal model
      to compare parasitology within a single species with contrasting life histories.
      Currently, little information exists on the presence and impacts of parasites in
      these fish populations; the present study sets out to better understand
      coccidiosis in the threatened anadromous populations and to understand how
      coccidian parasites compare in both life history forms. The intestinal coccidian,
      Goussia ameliae n. sp., was described infecting the pyloric cecum of 76% and 86%
      of young-of-the-year and adult anadromous alewives, respectively, from the
      Maurice River, New Jersey, USA. The coccidian was found in landlocked alewife
      populations with a prevalence of 92% and 34% in YOY and adult fish, respectively.
      An analysis of the small subunit 18S ribosomal RNA gene of G. ameliae from both
      life history forms demonstrated that the coccidian had 100% sequence identity,
      confirming the same parasite species in both forms. Though genetic analysis
      demonstrated G. ameliae to be identical, some differences were observed in
      sporulation and morphology of the parasite within the two populations. The
      sporocysts in anadromous populations were shorter and wider, and sporulation
      timing differed from that of landlocked fish. These differences may either be
      attributed to differences in the host type or to the sporulation environment.
      Lastly, alewives from landlocked populations were frequently co-infected with a
      second coccidian species in the posterior intestine, which occurred at a lower
      prevalence. This species, G. alosii n. sp., was described based on morphological
      characters of the sporulated oocysts in fresh parasitological preparations. 

PMID- 25853052
TI  - Parasites of wildlife - Special issue.

PMID- 25853053
TI  - Epidemiology and molecular phylogeny of Babesia sp. in Little Penguins Eudyptula
      minor in Australia.
AB  - Blood parasites are potential threats to the health of penguins and to their
      conservation and management. Little penguins Eudyptula minor are native to
      Australia and New Zealand, and are susceptible to piroplasmids (Babesia),
      hemosporidians (Haemoproteus, Leucocytozoon, Plasmodium) and kinetoplastids
      (Trypanosoma). We studied a total of 263 wild little penguins at 20 sites along
      the Australian southeastern coast, in addition to 16 captive-bred little
      penguins. Babesia sp. was identified in seven wild little penguins, with positive
      individuals recorded in New South Wales, Victoria and Tasmania. True prevalence
      was estimated between 3.4% and 4.5%. Only round forms of the parasite were
      observed, and gene sequencing confirmed the identity of the parasite and
      demonstrated it is closely related to Babesia poelea from boobies (Sula spp.) and
      B. uriae from murres (Uria aalge). None of the Babesia-positive penguins
      presented signs of disease, confirming earlier suggestions that chronic
      infections by these parasites are not substantially problematic to otherwise
      healthy little penguins. We searched also for kinetoplastids, and despite
      targeted sampling of little penguins near the location where Trypanosoma
      eudyptulae was originally reported, this parasite was not detected. 

PMID- 25853051
TI  - Species of Angiostrongylus (Nematoda: Metastrongyloidea) in wildlife: A review.
AB  - Twenty-one species of Angiostrongylus plus Angiostrongylus sp. (Nematoda:
      Metastrongyloidea) are known currently in wildlife. These occur naturally in
      rodents, tupaiids, mephitids, mustelids, procyonids, felids, and canids, and
      aberrantly in a range of avian, marsupial and eutherian hosts including humans.
      Adults inhabit the pulmonary arteries and right atrium, ventricle and vena cava,
      bronchioles of the lung or arteries of the caecum and mesentery. All species pass
      first-stage larvae in the faeces of the host and all utilise slugs and/or aquatic
      or terrestrial snails as intermediate hosts. Gastropods are infected by ingestion
      or penetration of first-stage larvae; definitive hosts by ingestion of gastropods
      or gastropod slime. Transmission of at least one species may involve ingestion of
      paratenic hosts. Five developmental pathways are identified in these life cycles.
      Thirteen species, including Angiostrongylus sp., are known primarily from the
      original descriptions suggesting limited geographic distributions. The remaining
      species are widespread either globally or regionally, and are continuing to
      spread. Small experimental doses of infective larvae (ca. 20) given to normal or
      aberrant hosts are tolerated, although generally eliciting a granulomatous
      histopathological response; large doses (100-500 larvae) often result in clinical
      signs and/or death. Two species, A. cantonensis and A. costaricensis, are
      established zoonoses causing neurological and abdominal angiostrongliasis
      respectively. The zoonotic potential of A. mackerrasae, A. malaysiensis and A.
      siamensis particularly warrant investigation. Angiostrongylus cantonensis occurs
      in domestic animals, mammalian and avian wildlife and humans in the metropolitan
      areas of Brisbane and Sydney, Australia, where it has been suggested that tawny
      frogmouths and brushtail possums may serve as biosentinels. A major conservation
      issue is the devastating role A. cantonensis may play around zoos and fauna parks
      where captive rearing of endangered species programmes may exist and where Rattus
      spp. are invariably a problem. 

PMID- 25853054
TI  - Evidence for Natural Selection in Nucleotide Content Relationships Based on
      Complete Mitochondrial Genomes: Strong Effect of Guanine Content on Separation
      between Terrestrial and Aquatic Vertebrates.
AB  - The complete vertebrate mitochondrial genome consists of 13 coding genes. We used
      this genome to investigate the existence of natural selection in vertebrate
      evolution. From the complete mitochondrial genomes, we predicted nucleotide
      contents and then separated these values into coding and non-coding regions. When
      nucleotide contents of a coding or non-coding region were plotted against the
      nucleotide content of the complete mitochondrial genomes, we obtained linear
      regression lines only between homonucleotides and their analogs. On every plot
      using G or A content purine, G content in aquatic vertebrates was higher than
      that in terrestrial vertebrates, while A content in aquatic vertebrates was lower
      than that in terrestrial vertebrates. Based on these relationships, vertebrates
      were separated into two groups, terrestrial and aquatic. However, using C or T
      content pyrimidine, clear separation between these two groups was not obtained.
      The hagfish (Eptatretus burgeri) was further separated from both terrestrial and
      aquatic vertebrates. Based on these results, nucleotide content relationships
      predicted from the complete vertebrate mitochondrial genomes reveal the existence
      of natural selection based on evolutionary separation between terrestrial and
      aquatic vertebrate groups. In addition, we propose that separation of the two
      groups might be linked to ammonia detoxification based on high G and low A
      contents, which encode Glu rich and Lys poor proteins. 

PMID- 25853055
TI  - A facile method for simultaneously measuring neuronal cell viability and neurite
      outgrowth.
AB  - Neurite outgrowth is an important morphological phenotype of neuronal cells that
      correlates with their function and cell health, yet there are limited methods
      available for measuring this phenomenon. Current approaches to measuring neurite
      outgrowth are laborious and time-consuming, relying largely upon
      immunocytochemical staining of neuronal markers (e.g., beta-III tubulin or MAP2)
      followed by manual or automated microscopy for image acquisition and analysis.
      Here we report the development of a quick and simple dual-color fluorescent dye
      based staining method that allows for the simultaneous measurement of neuronal
      cell health and relative neurite outgrowth from the same sample. An orangered
      fluorescent dye that stains cell membrane surfaces is used as an indirect
      reporter of changes in relative neurite outgrowth due to alterations in the
      number or length of membrane projections emanating from neuronal cell bodies.
      Cell viability is assessed simultaneously via the use of a cell-permeant dye that
      is converted by intracellular esterase activity from a non-fluorescent substrate
      to a green-fluorescent product. Using Neuroscreen-1 cells (a PC-12 subclone),
      primary rat cortex neurons, and human induced pluripotent stem cell (iPSC)
      derived neurons, we demonstrate that this multiplex assay allows for rapid
      visualization and unbiased, quantitative plate reader analysis of neuronal cell
      health and neurite outgrowth. 

PMID- 25853056
TI  - Association of ADIPOQ, OLR1 and PPARGC1A gene polymorphisms with growth and
      carcass traits in Nelore cattle.
AB  - In beef cattle farming, growth and carcass traits are important for genetic
      breeding programs. Molecular markers can be used to assist selection and increase
      genetic gain. The ADIPOQ, OLR1 and PPARGC1A genes are involved in lipid synthesis
      and fat accumulation in adipose tissue. The objective of this study was to
      identify polymorphisms in these genes and to assess the association with growth
      and carcass traits in Nelore cattle. A total of 639 animals were genotyped by PCR
      RFLP for rs208549452, rs109019599 and rs109163366 in ADIPOQ, OLR1 and PPARGC1A
      gene, respectively. We analyzed the association of SNPs identified with birth
      weight, weaning weight, female yearling weight, female hip height, male yearling
      weight, male hip height, loin eye area, rump fat thickness, and backfat
      thickness. The OLR1 marker was associated with rump fat thickness and weaning
      weight (P < 0.05) and the PPARGC1 marker was associated with female yearling
      weight. 

PMID- 25853057
TI  - IRF6 polymorphisms in Mexican patients with non-syndromic cleft lip.
AB  - Cleft lip with or without cleft palate (CL/P) is one of the most common birth
      defects; it is a multifactorial disease affecting > 1/1,000 live births in
      Europe, and its etiology is largely unknown, although it is very likely genetic
      and environmental factors contribute to this malformation. Orofacial development
      is a complex process involving many genes and signaling pathways. Mutations in
      the gene for the interferon regulatory factor 6 (IRF6) cause a hereditary
      dominant malformation syndrome including CL/P, and polymorphisms are associated
      with non-syndromic CL/P (MIM 119530). Five SNPs at the locus with high
      heterozygosity in Caucasian populations were chosen for the present research due
      to their very strong association with CL/P. A case-parent trio study was
      performed using 292 samples from Mexico. Association with the rs1319435-C/C
      genotype (P = 0.02) was found in patients (73) as compared to pseudocontrols
      (219), while the genotype rs1319435-T/C was related with protection (P = 0.041)
      in the triad design. Significant over-transmission of the G allele for marker
      rs2235375 (P = 0.049) was found. Only the TACGT haplotype was diminished in the
      affected child, either in single (P = 0.0208) or double (P = 0.0208) dose. The
      pairwise analysis showed rs2235543 and rs2235371 were in strong linkage
      disequilibrium. These results point to a substantial contribution of IRF6 in the
      etiology of non-syndromic CL/P in a sample of the Mexican population. 

PMID- 25853058
TI  - Mitochondrial COI and nuclear RAG1 DNA sequences and analyses of specimens of the
      three morphologically established species in the genus Trichopsis (Perciformes:
      Osphronemidae) reveal new/cryptic species.
AB  - Air-breathing fish species of the genus Trichopsis have been reported in
      Cambodia, Lao PDR, Indonesia, Malaysia, Singapore, Thailand and Vietnam. It is
      only in Thailand that all three recognized species (Trichopsis vittata,
      Trichopsis schalleri and Trichopsis pumila), as judged by distinct external
      features, are found. Cambodia and Lao PDR harbor two species each. The present
      work involves first-time DNA sequencing and analysis based on mitochondrial (COI)
      and nuclear (RAG1) DNA of numerous specimens of these species and specimens of a
      controversial Phetchaburi (Thailand) fish population with a mixed outward
      appearance. In addition to confirming the morphologically clear-cut taxonomic
      division of the three fish species, our DNA results show that whereas the T.
      pumila populations form one single species, there are cryptic species in the T.
      vittata and T. schalleri populations and possibly a new one in the latter.
      Members of the putative Phetchaburi fish population have been proven to be
      hybrids between T. pumila and T. vittata. In addition, a new the phylogenetic
      tree indicating ancestral relationships is also presented. This study should
      generate further research to find new/cryptic species of the genus Trichopsis in
      all countries harboring the fish. 

PMID- 25853059
TI  - Characterization of KfrA proteins encoded by a plasmid of Paenibacillus popilliae
      ATCC 14706(T).
AB  - A scaffold obtained from whole-genome shotgun sequencing of Paenibacillus
      popilliae ATCC 14706(T) shares partial homology with plasmids found in other
      strains of P. popilliae. PCR and sequencing for gap enclosure indicated that the
      scaffold originated from a 15,929-bp circular DNA. The restriction patterns of a
      plasmid isolated from P. popilliae ATCC 14706(T) were identical to those expected
      from the sequence; thus, this circular DNA was identified as a plasmid of ATCC
      14706(T) and designated pPOP15.9. The plasmid encodes 17 putative open reading
      frames. Orfs 1, 5, 7, 8, and 9 are homologous to Orfs 11, 12, 15, 16, and 17,
      respectively. Orf1 and Orf11 are annotated as replication initiation proteins.
      Orf8 and Orf16 are homologs of KfrA, a plasmid-stabilizing protein in Gram
      negative bacteria. Recombinant Orf8 and Orf16 proteins were assessed for the
      properties of KfrA. Indeed, they formed multimers and bound to inverted repeat
      sequences in upstream regions of both orf8 and orf16. A phylogenetic tree based
      on amino acid sequences of Orf8, Orf16 and Kfr proteins did not correlate with
      species lineage. 

PMID- 25853060
TI  - Association of novel SNPs in the candidate genes affecting caprine milk fatty
      acids related to human health.
AB  - In the present investigation, 618 milk samples of Sirohi breed of goat were
      collected, and analyzed for conjugated linoleic acid (CLA, C18:2) and other fatty
      acids. The CLA in studied goat milk samples was 4.87 mg/g of milk fat and C18:2
      cis-9, trans-11 contributes 2.9 mg/g of milk fat and trans10 cis12 contributes
      0.82 mg/g of milk fat. The saturated fatty acids in the milk accounted for 69.55%
      and unsaturated fatty acid accounted for 28.50%. The unsaturated fatty acid was
      constituted by monounsaturated fatty acid (24.57%) and polyunsaturated fatty
      acids (3.96%.). The major contribution (45.56%) in total fatty acid was of C12:0,
      C14:0 and C16:0. C18:0 and short chain ones (C4:0, C6:0, C8:0, and C10:0) have a
      neutral or cholesterol-decreasing effect. The DNA sequence analysis of the genes
      (DGAT1, SCAP, PPARG, OLR, FABP3 and PRL) in a random panel of 8 Sirohi goats
      revealed 38 SNPs across the targeted regions. Out of the studied SNPs (38) across
      these genes, 22 SNPs had significant effect on one or a group of fatty acids
      including CLA. The genotypes at these loci showed significant differences in the
      least square means of a particular fatty acid or a group of fatty acids including
      CLA and its isomers. 

PMID- 25853061
TI  - KIR genotype distribution among Lebanese patients with Hodgkin's lymphoma.
AB  - INTRODUCTION: In addition to their important role in fighting infection, natural
      killer cells are cytotoxic to cancer cells. Studies demonstrated that some KIR
      genes were responsible for the reduction of the risk of Hodgkin's lymphoma (HL)
      while others were associated with an increased risk of HL. AIM: The aim of this
      study is to assess KIR genotypic distribution in Lebanese patients with Hodgkin's
      lymphoma. METHODS: KIR genotype was analyzed in 41 HL patients and 120 healthy
      Lebanese individuals using the KIR Genotyping SSP kit. RESULTS: No significant
      association between HL and any KIR gene was found. Among HL patients, the AA, AB,
      and BB genotype frequencies were, respectively, 41.46%, 43.9% and 14.63% with an
      A:B ratio of 1.73:1. As for the controls, the AA, AB, and BB genotype frequencies
      were, respectively, 39.17%, 50%, and 10.83% with an A:B ratio of 1.79:1.
      CONCLUSION: In this first study from the Mediterranean region, KIR genotype does
      not seem to be associated with Hodgkin's lymphoma. Further clinical and
      translational research is needed to rule out the protective or predisposing role
      of KIR genes in this important clinical entity.

PMID- 25853063
TI  - Synthesis and Antimicrobial Activity of 6-Thioxo-6,7-dihydro-2H
      [1,2,4]triazino[2,3-c]-quinazolin-2-one Derivatives.
AB  - Potassium 8-R(1)-9-R(2)-10-R(3)-3-R-2-oxo-2H-[1,2,4]triazino[2,3-c]quinazoline-6
      thiolates 2.1-2.26 were synthesized via cyclocondensation of 6-R-3-(3-R(1)-4-R(2)
      5-R(3)-aminophenyl)-1,2,4-triazin-5-ones 1.1-1.26 with carbon disulfide,
      potassium hydroxide, and ethanol or with potassium O-ethyl dithiocarbonate in 2
      propanol. The corresponding thiones 3.1-3.26 were obtained by treatment of 2.1
      2.26 with hydrochloric acid. It was found that the nature of the substituents in
      positions 3, 4, and 5 of the corresponding 6-R-3-(3-R(1)-4-R(2)-5-R(3)
      aminophenyl)-1,2,4-triazin-5-ones were affected on the terms of the reaction. The
      structures of compounds were proven by a complex of physicochemical methods
      ((1)H, (13)C NMR, LC-MS, and EI-MS). The results of the antibacterial and
      antifungal activity assay allowed the determination of the high sensitivity of
      Staphylococcus aureus ATCC 25923 (MIC 6.25-100 MUg/mL, MBC 12.5-200 MUg/mL) to
      the synthesized compounds.

PMID- 25853062
TI  - Selective Phosphodiesterase 4B Inhibitors: A Review.
AB  - Phosphodiesterase 4B (PDE4B) is a member of the phosphodiesterase family of
      proteins that plays a critical role in regulating intracellular levels of cyclic
      adenosine monophosphate (cAMP) by controlling its rate of degradation. It has
      been demonstrated that this isoform is involved in the orchestra of events which
      includes inflammation, schizophrenia, cancers, chronic obstructive pulmonary
      disease, contractility of the myocardium, and psoriatic arthritis.
      Phosphodiesterase 4B has constituted an interesting target for drug development.
      In recent years, a number of PDE4B inhibitors have been developed for their use
      as therapeutic agents. In this review, an up-to-date status of the inhibitors
      investigated for the inhibition of PDE4B has been given so that this rich source
      of structural information of presently known PDE4B inhibitors could be helpful in
      generating a selective and potent inhibitor of PDE4B.

PMID- 25853064
TI  - Short and Efficient Synthesis of Alkyl- and Aryl-Ortho-Hydroxy-Anilides and their
      Antibiotic Activity.
AB  - Ortho-hydroxy-anilides are part of natural products like the new antibiotics
      platencin (A) and platensimycin (B). An important step in the total synthesis of
      these antibiotics or their derivatives is the preparation of the o-hydroxy
      anilide partial structure. The presented method allows the preparation of o
      hydroxy-anilides and o-dihydroxy-anilides from 2-nitrophenol esters in a one-step
      synthesis without protecting the hydroxy group. Aryl- and alkyl-anilides were
      prepared following this method as simple analogues of platensimycin (A). The
      resulting compounds were tested in an agar diffusion assay for their antibiotic
      potency.

PMID- 25853065
TI  - Quality by Design-Based Development of a Stability-Indicating RP-HPLC Method for
      the Simultaneous Determination of Methylparaben, Propylparaben, Diethylamino
      Hydroxybenzoyl Hexyl Benzoate, and Octinoxate in Topical Pharmaceutical
      Formulation.
AB  - A stability-indicating RP-HPLC method has been developed and validated for the
      simultaneous determination of methylparaben (MP), propylparaben (PP),
      diethylamino hydroxybenzoyl hexyl benzoate (DAHHB), and octinoxate (OCT) in
      topical pharmaceutical formulation. The desired chromatographic separation was
      achieved on the Kinetex(TM) C18 (250 * 4.6 mm, 5 MUm) column using gradient
      elution at 257 nm detection wavelength. The optimized mobile phase consisted of a
      buffer : acetonitrile : tetrahydrofuran (60 : 30 : 10, v/v/v) as solvent A and
      acetonitrile : tetrahydrofuran (70 : 30, v/v) as solvent B. The method showed
      linearity over the range of 0.19-148.4 MUg/mL, 0.23-15.3 MUg/mL, 1.97-600.5
      MUg/mL, and 1.85-451.5 MUg/mL for MP, PP, DAHHB, and OCT, respectively. Recovery
      for all the components was found to be in the range of 98-102%. The stability
      indicating capability of the developed method was established by analysing the
      forced degradation samples in which the spectral purity of MP, PP, DAHHB, and
      OCT, along with the separation of the degradation products from the analyte
      peaks, was achieved. The proposed method was successfully applied for the
      quantitative determination of MP, PP, DAHHB, and OCT in the lotion sample. The
      design expert with ANOVA software with the linear model was applied and a 2(4)
      full factorial design was employed to estimate the model coefficients and also to
      check the robustness of the method. Results of the two-level full factorial
      design, 2(4) with 20 runs including four centrepoint analysis based on the
      variance analysis (ANOVA), demonstrated that all four factors, as well as the
      interactions of resolution between DAHHB and OCT are statistically significant.

PMID- 25853066
TI  - Validated Stability-Indicating RP-HPLC Method for the Simultaneous Determination
      of Azelnidipine and Olmesartan in Their Combined Dosage Form.
AB  - A simple, rapid, and highly selective RP-HPLC method was developed for the
      simultaneous determination of Azelnidipine (AZL) and Olmesartan (OLM) drug
      substances in the fixed dosage strength of 16 mg and 20 mg, respectively.
      Effective chromatographic separation was achieved using a Hypersil GOLD C18
      column (150 mm * 4.6 mm internal diameter, 5 um particle size) with a mobile
      phase composed of methanol, acetonitrile, and water in the ratio of 40:40:20 (by
      volume). The mobile phase was pumped using a gradient HPLC system at a flow rate
      of 0.5 mL/min, and quantification of the analytes was based on measuring their
      peak areas at 260 nm. The retention times for Azelnidipine and Olmesartan were
      about 8.56 and 3.04 min, respectively. The reliability and analytical performance
      of the proposed HPLC procedure were statistically validated with respect to
      system suitability, linearity, ranges, precision, accuracy, specificity,
      robustness, detection, and quantification limits. Calibration curves were linear
      in the ranges of 2-48 MUg/mL for Azelnidipine and 2.5-60 MUg/mL for Olmesartan
      with correlation coefficients >0.990. The proposed method proved to be selective
      and stability-indicating by the resolution of the two analytes from the forced
      degradation (hydrolysis, oxidation, and photolysis) products. The validated HPLC
      method was successfully applied to the analysis of AZL and OLM in their combined
      dosage form.

PMID- 25853067
TI  - Reflections on Decisions Made on the Well-Established Use of Medicinal Products
      by EU Regulators and the ECJ.
AB  - BACKGROUND: In the European Union (EU), a medicinal product needs a marketing
      authorization (MA) to be placed on the market. The EU's medicinal products'
      legislative framework allows for a reduced application for medicines outside
      their data exclusivity. One such type of application is the well-established use
      (WEU) medicinal product application (i.e. bibliographic applications). Recently,
      these MA applications have been subject to arbitration procedures at the European
      Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) because
      of disagreements between member states during the authorisation process. This
      paper reflects on these cases and highlights their potential impact on future WEU
      applications. METHODS: Decisions adopted by the European Commission on WEU
      applications between 2009 and 2012 were identified from the EU Community Register
      on medicinal products for human use. Subsequently, decisions were reviewed to
      understand the potential serious risk to public health (PSRPH) that EU regulators
      raised during MA application procedures. RESULTS: Four decisions were adopted by
      the EU commission between 2009 and 2012. Three followed disagreements between
      member states on PSRPH grounds. One decision was the outcome of a centralised
      marketing authorisation application. Six key messages were identified from the
      four cases reviewed and presented. CONCLUSION: A guideline on WEU to implement
      the technical specifications to fulfil Annex I of Directive 2001/83/EC for MA
      applications is not available. Thus, reflections on recent decisions on WEU
      applications provide scientific direction to the industry as well as the
      medicinal product regulators on the documentation required to successfully file
      and obtain a WEU MA.

PMID- 25853068
TI  - HPLC-DAD Method for the Pharmacokinetic Interaction Study of Atorvastatin with
      Pioglitazone and Cholestyramine in Wistar Rats.
AB  - Carotid intima-media thickness is used as a surrogate marker for cardiovascular
      complications in diabetes mellitus. The combination of atorvastatin and
      pioglitazone was found to be effective in reducing the thickness of the carotid
      intima-media layer. The method of RP-HPLC coupled with a diode array detector
      (DAD) was developed for the pharmacokinetic interaction study of atorvastatin
      with pioglitazone and cholestyramine, respectively, in Wistar rats. Atorvastatin
      (ATR) and pioglitazone (PIO) were resolved on a C18 column with a mobile phase
      composed of 48% methanol, 19% acetonitrile, and 33% 10 mM ammonium formate
      (v/v/v; pH 3.5+/-0.3, by formic acid) and a 260 nm detection wavelength on the
      diode array detector. The method was validated according to international
      standards with good reproducibility and linear response; mean (r) 0.9987 and
      0.9972 to ATR and PIO, respectively. The coefficients of variation of intra- and
      interassay precision ranged between 4.95-8.12 and 7.29-9.67, respectively.
      Pharmacokinetic parameters were determined in rats following an oral
      administration of atorvastatin in the presence and absence of pioglitazone and
      also with cholestyramine. Compared with the control given atorvastatin alone, the
      Cmax and AUC of atorvastatin were merely unchanged in rats with the co
      administration of pioglitazone, while they decreased by nearly 21 and 15%,
      respectively, with the concurrent use of cholestyramine. There were no
      significant changes in Tmax and the plasma half-life (T1/2 ) of atorvastatin in
      both cases. The performed experiment demonstrated that the presented method was
      suitable for the estimation and pharmacokinetic interaction study of atorvastatin
      with pioglitazone and cholestyramine in Wistar rat plasma.

PMID- 25853069
TI  - Development and validation of a liquid chromatography-mass spectrometry method
      for the determination of zileuton in human plasma.
AB  - A selective and sensitive liquid chromatography-tandem mass spectrometric method
      (LC-MS/MS) has been developed and validated for the quantification of zileuton in
      human plasma. Deuterated internal standard (zileuton D4) was used as the internal
      standard (ISTD). Zileuton was extracted by liquid-liquid extraction using methyl
      tert-butyl ether and separated by isocratic elution on a C18 column (100 * 4.6
      mm, 5 MUm, Discovery C18) with the mobile phase consisting of 1 mM ammonium
      acetate buffer and methanol in the ratio of 10:90. A flow rate of 1.0 ml/min was
      used with isocratic elution. Multiple reaction monitoring transitions in positive
      mode for zileuton and the internal standard were 237.3/161.2 and 241.2/161.1,
      respectively. The method was validated within the linearity range of 50.5
      10,012.7 ng/ml for the bioanalytical method validation parameters like
      selectivity, accuracy, precision, recovery, stability, and matrix effect.

PMID- 25853070
TI  - Development and Validation of a LC-MS/MS Method for the Simultaneous Estimation
      of Amlodipine and Valsartan in Human Plasma: Application to a Bioequivalence
      Study.
AB  - A reliable, simple, and robust liquid chromatography-tandem mass spectro-metric
      (LC-MS/MS) method has been developed and validated that employs solid-phase
      extraction for the simultaneous estimation of amlodipine and valsartan in human
      K3EDTA plasma using amlodipine-d4 and valsartan-d9 as internal standards.
      Chromatographic separation of amlodipine and valsartan was achieved on the Luna
      C18 (2)100A (150 * 4.6 mm, 5 MUm) column using acetonitrile: 5 mM ammonium
      formate solution (80:20, v/v) as the mobile phase at a flow rate of 0.8 mL/min in
      isocratic mode. Quantification was achieved using an electrospray ion interface
      operating in positive mode, under multiple reaction monitoring (MRM) conditions.
      The assay was found to be linear over the range of 0.302-20.725 ng/mL for
      amlodipine and 6.062-18060.792 ng/mL for valsartan. The method has shown good
      reproducibility, as intra- and interday precisions were within 10% and accuracies
      were within 8% of nominal values for both analytes. The method was successfully
      applied for the bioequivalence study of amlodipine and valsartan after oral
      administration of a fixed dose of the combination. Additionally, as required by
      the current regulatory bodies, incurred sample reanalysis was performed and found
      to be acceptable.

PMID- 25853071
TI  - New Chemometrics Mode Based on Adjacent Data Points' Differences for the
      Simultaneous Determination of Clopidogrel, Atorvastatin, and Aspirin in their
      Combined Ternary Drug Formulation.
AB  - A new method is proposed for the analysis of a ternary mixture composed of
      clopidogrel, atorvastatin, and aspirin without prior separation steps. The method
      combines the advantages of the mean centering of ratio spectra and derivative
      spectrophotometric methods. It is based on using the difference between adjacent
      data points in the absorbance spectra. The principal advantage of this method is
      the use of absorbance data, and not derivative data; hence the signal-to-noise
      ratio is not diminished. The mathematical explanation of the procedure is
      illustrated. Beer's law was valid in the concentration range 0.3-35 MUg.mL(-1)
      for CLOP, 0.5-30 MUg.mL(-1) for ATOR, and 1-40 MUg.mL(-1) for ASP. Mean
      recoveries were obtained as 100.2, 100.1, and 100.2% for CLOP, ATOR, and ASP,
      respectively, in the prepared synthetic mixtures. The method has been
      successfully applied to the simultaneous determination of ternary mixtures of
      aspirin, clopidogrel bisulphate, and atorvastatin calcium. The analytical
      characteristics of the method were calculated. The results showed that the new
      method is simple, rapid, accurate, and precise.

PMID- 25853072
TI  - An Experimental Design Approach for Impurity Profiling of Valacyclovir-Related
      Products by RP-HPLC.
AB  - Impurity profiling has become an important phase of pharmaceutical research where
      both spectroscopic and chromatographic methods find applications. The analytical
      methodology needs to be very sensitive, specific, and precise which will separate
      and determine the impurity of interest at the 0.1% level. Current research
      reports a validated RP-HPLC method to detect and separate valacyclovir-related
      impurities (Imp-E and Imp-G) using the Box-Behnken design approach of response
      surface methodology. A gradient mobile phase (buffer: acetonitrile as mobile
      phase A and acetonitrile: methanol as mobile phase B) was used. Linearity was
      found in the concentration range of 50-150 MUg/mL. The mean recovery of
      impurities was 99.9% and 103.2%, respectively. The %RSD for the peak areas of Imp
      E and Imp-G were 0.9 and 0.1, respectively. No blank interferences at the
      retention times of the impurities suggest the specificity of the method. The LOD
      values were 0.0024 MUg/mL for Imp-E and 0.04 MUg/mL for Imp-G and the LOQ values
      were obtained as 0.0082 MUg/mL and 0.136 MUg/mL, respectively, for the
      impurities. The S/N ratios in both cases were within the specification limits.
      Proper peak shapes and satisfactory resolution with good retention times
      suggested the suitability of the method for impurity profiling of valacyclovir
      related drug substances.

PMID- 25853073
TI  - Lack of Association between the Serotonin Transporter (5-HTT) and Serotonin
      Receptor (5-HT2A) Gene Polymorphisms with Smoking Behavior among Malaysian
      Malays.
AB  - An insertion/deletion polymorphism in the promoter region of the serotonin
      transporter gene (5-HTTLPR) and a polymorphism (rs6313) in the serotonin 2A
      receptor gene (5-HT2A) have previously been linked to smoking behavior. The
      objective of this study was to determine the possible association of the 5-HTTLPR
      and 5-HT2A gene polymorphisms with smoking behavior within a population of
      Malaysian male smokers (n=248) and non-smokers (n=248). The 5-HTTLPR genotypes
      were determined using the polymerase chain reaction (PCR) and were classified as
      short (S) alleles or long (L) alleles. The 5HT2A genotypes were determined using
      PCR-restriction fragment length polymorphisms (PCR-RFLP). No significant
      differences in the distribution frequencies of the alleles were found between the
      smokers and the non-smokers for the 5-HTTLPR polymorphism (x(2) = 0.72, P>0.05)
      or the 5HT2A polymorphism (x(2) = 0.73, P>0.05). This is the first study
      conducted on Malaysian Malay males regarding the association of 5-HTTLPR and
      5HT2A polymorphisms and smoking behavior. However, the genes were not found to be
      associated with smoking behavior in our population.

PMID- 25853074
TI  - Evaluation of the anticonvulsant and anxiolytic potentials of methyl jasmonate in
      mice.
AB  - Methyl jasmonate (MJ) is one of the most well-studied plant stress hormones
      belonging to the jasmonate family. Previous studies have shown that MJ
      potentiated pentobarbitone sleeping time and enhanced GABA-mediated inhibitory
      neurotransmission, suggesting potential benefits in disorders associated with
      hyperactivity of the brain. This study was carried out to evaluate whether MJ has
      anticonvulsant and anxiolytic properties in mice. The anticonvulsant effect was
      assessed based on the prevention of tonic-clonic seizures induced by
      chemoconvulsant agents in mice. The anxiolytic property was evaluated utilizing
      the elevated plus maze (EPM) and light/dark transition paradigms. The effect of
      MJ on spontaneous locomotor activity (SMA) was also assessed. Mice received
      intraperitoneal (i.p.) injections of MJ 30 min before the tests were carried out
      and diazepam (2 mg/kg, i.p.) was used as the reference drug. MJ (50-400 mg/kg)
      did not protect the mice against tonic-clonic convulsions induced by picrotoxin
      (10 mg/kg, i.p.) or strychnine (3 mg/kg, i.p.). However, MJ (100, 200, and 400
      mg/kg) offered 20, 60, and 100% protection against pentylenetetrazole (100 mg/kg,
      i.p.)-induced convulsions. In a similar manner to diazepam (2 mg/kg), MJ (400
      mg/kg) produced a marked sedative effect as shown by decreases in the number of
      lines crossed and the duration of ambulation in the open field test. In contrast
      to diazepam (2 mg/kg), MJ (5-50 mg/kg) did not show anxiolytic effects in the EPM
      and light/dark transition paradigms. These findings suggest that methyl jasmonate
      at high doses possessed anticonvulsant properties in the pentylenetetrazole
      animal model of epilepsy, but did not produce anxiolytic activity in mice.

PMID- 25853075
TI  - Preparation, in vitro characterization, and in vivo pharmacokinetic evaluation of
      respirable porous microparticles containing rifampicin.
AB  - This study aimed to prepare and evaluate rifampicin microparticles for the lung
      delivery of rifampicin as respirable powder. The microparticles were prepared
      using chitosan by the spray-drying method and evaluated for aerodynamic
      properties and pulmonary drug absorption. To control the drug release, tripoly
      phosphate in different concentrations 0.6, 0.9, 1.2, and 1.5 was employed to get
      a sustained drug release profile. The microparticles were evaluated for drug
      loading, % entrapment efficiency, tapped density, morphological characteristics,
      and in vitro drug release studies. Aerosol properties were determined using the
      Andersen cascade impactor. Porous microparticles with particle sizes (d0.5) less
      than 10 MUm were obtained. The entrapment of rifampicin in microparticles was up
      to 72%. In vitro drug release suggested that the crosslinked microparticles
      showed sustained release for more than 12 hrs. The drug release rate was found to
      be decreased as the TPP concentration was increased. The microparticles showed a
      fine particle fraction in the range of 55-63% with mass median aerodynamic
      diameter (MMAD) values below 3 MUm. The in vivo pulmonary absorption of the
      chitosan microparticles suggested a sustained drug release profile up to 72 hrs
      with an elimination rate of 0.010 per hr. The studies revealed that the spray
      dried porous microparticles have suitable properties to be used as respirable
      powder in rifampicin delivery to the lungs.

PMID- 25853076
TI  - Release kinetics of papaverine hydrochloride from tablets with different
      excipients.
AB  - The influence of excipients on the disintegration times of tablets and the
      release of papaverine hydrochloride (PAP) from tablets were studied. Ten
      different formulations of tablets with PAP were prepared by direct powder
      compression. Different binders, disintegrants, fillers, and lubricants were used
      as excipients. The release of PAP was carried out in the paddle apparatus using
      0.1 N HCl as a dissolution medium. The results of the disintegration times of
      tablets showed that six formulations can be classified as fast dissolving tablets
      (FDT). FDT formulations contained Avicel PH 101, Avicel PH 102, mannitol, (3
      lactose, PVP K 10, gelatinized starch (CPharmGel), Prosolv Easy Tab, Prosolv SMCC
      90, magnesium stearate, and the addition of disintegrants such as AcDiSol and
      Kollidon CL. Drug release kinetics were estimated by the zero- and first-order,
      Higuchi release rate, and Korsmeyer-Peppas models. Two formulations of the
      tablets containing PVP (K10) (10%), CPharmGel (10% and 25%), and Prosolv Easy Tab
      (44% and 60%) without the addition of a disintegrant were well-fitted to the
      kinetics models such as the Higuchi and zero-order, which are suitable for
      controlled- or sustained-release.

PMID- 25853077
TI  - Oral Immunization Against Candidiasis Using Lactobacillus casei Displaying
      Enolase 1 from Candida albicans.
AB  - Candidiasis is a common fungal infection that is prevalent in immunocompromised
      individuals. In this study, an oral vaccine against Candida albicans was
      developed by using the molecular display approach. Enolase 1 protein (Eno1p) of
      C. albicans was expressed on the Lactobacillus casei cell surface by using poly
      gamma-glutamic acid synthetase complex A from Bacillus subtilis as an anchoring
      protein. The Eno1p-displaying L. casei cells were used to immunize mice, which
      were later challenged with a lethal dose of C. albicans. The data indicated that
      the vaccine elicited a strong IgG response and increased the survival rate of the
      vaccinated mice. Furthermore, L. casei acted as a potent adjuvant and induced
      high antibody titers that were comparable to those induced by strong adjuvants
      such as the cholera toxin. Overall, the molecular display method can be used to
      rapidly develop vaccines that can be conveniently administered and require
      minimal processing.

PMID- 25853078
TI  - The role of magnetic resonance imaging techniques in the diagnosis, surgical
      treatment and biological understanding of epilepsy.

PMID- 25853079
TI  - Post-processing of structural MRI for individualized diagnostics.
AB  - Currently, a relevant proportion of all histopathologically proven focal cortical
      dysplasia (FCD) escape visual detection; this shows the need for additional
      improvements in analyzing MRI data. A positive MRI is still the strongest
      prognostic factor for postoperative freedom of seizures. Among several post
      processing methods voxel-based morphometry (VBM) of T1- and T2-weighted sequences
      and T2 relaxometry are routinely applied in pre-surgical diagnostics of
      cryptogenic epilepsy in epilepsy centers. VBM is superior to conventional visual
      analysis with 9-15% more identified epileptogenic foci, while T2 relaxometry has
      its main application in (mesial) temporal lobe epilepsy. Further methods such as
      surface-based morphometry (SBM) or diffusion tensor imaging are promising but
      there is a lack of current studies comparing their individual diagnostic value.
      Post-processing methods represent an important addition to conventional visual
      analysis but need to be interpreted with expertise and experience so that they
      should be apprehended as a complementary tool within the context of the multi
      modal evaluation of epilepsy patients. This review will give an overview of
      existing post-processing methods of structural MRI and outline their clinical
      relevance in detection of epileptogenic structural changes. 

PMID- 25853081
TI  - Quantifying the deficit-imaging neurobehavioural impairment in childhood
      epilepsy.
AB  - BACKGROUND: Neurobehavioral impairments such as learning difficulty, autism,
      attention deficit hyperactivity disorder (ADHD) and mood or behavioural problems
      are known to be increased in children with epilepsy; however, they remain under
      recognised and often cause considerable morbidity. Quantitative neuroimaging
      techniques offer a potential avenue to improving our understanding of the
      underlying pathological basis for these disorders, aiding with diagnosis and risk
      stratification. METHODS: A systematic review was undertaken for original research
      articles involving magnetic resonance imaging in children with epilepsy and one
      or more neurobehavioural impairments. Studies were reviewed with respect to
      patient population, methodology and magnetic resonance imaging (MRI) findings.
      RESULTS: A total of 25 studies were identified and included in this review. The
      majority of studies looked at single impairments, commonly cognitive impairment
      or ADHD, with few studies reporting on other impairments. Reductions in cortical
      grey matter and disruptions of functional and structural brain networks were
      associated with poorer cognitive performance and disruptions of grey and white
      matter within a fronto-striatal-cerebellar network associated with ADHD.
      Insufficient studies were available to report on other impairments. CONCLUSIONS:
      Relatively few studies exist in this field and those that do are methodologically
      diverse. Further investigation is required to determine if the changes reported
      to date are epilepsy syndrome specific or have broader applicability.

PMID- 25853082
TI  - The effects of antiepileptic drugs on cognitive functional magnetic resonance
      imaging.
AB  - The cognitive dysfunction caused by antiepileptic drugs (AEDs) has been
      extensively described, although the mechanisms underlying such collateral effects
      are still poorly understood. The combination of functional magnetic resonance
      imaging (fMRI) studies with pharmacological intervention (pharmaco-MRI or ph-MRI)
      offers the opportunity to investigate the effect of drugs such as AEDs on brain
      activity, including cognitive tasks. Here we review the studies that investigated
      the effects of AEDs [topiramate (TPM), lamotrigine (LMT), carbamazepine (CBZ),
      pregabalin (PGB), valproate (VPA) and levetiracetam (LEV)] on cognitive fMRI
      tasks. Despite the scarcity of fMRI studies focusing on the impact of AEDs on
      cognitive task, the results of recent work have provided important information
      about specific drug-related changes of brain function. 

PMID- 25853080
TI  - Quantitative MRI in refractory temporal lobe epilepsy: relationship with surgical
      outcomes.
AB  - Medically intractable temporal lobe epilepsy (TLE) remains a serious health
      problem. Across treatment centers, up to 40% of patients with TLE will continue
      to experience persistent postoperative seizures at 2-year follow-up. It is
      unknown why such a large number of patients continue to experience seizures
      despite being suitable candidates for resective surgery. Preoperative
      quantitative MRI techniques may provide useful information on why some patients
      continue to experience disabling seizures, and may have the potential to develop
      prognostic markers of surgical outcome. In this article, we provide an overview
      of how quantitative MRI morphometric and diffusion tensor imaging (DTI) data have
      improved the understanding of brain structural alterations in patients with
      refractory TLE. We subsequently review the studies that have applied quantitative
      structural imaging techniques to identify the neuroanatomical factors that are
      most strongly related to a poor postoperative prognosis. In summary, quantitative
      imaging studies strongly suggest that TLE is a disorder affecting a network of
      neurobiological systems, characterized by multiple and inter-related limbic and
      extra-limbic network abnormalities. The relationship between brain alterations
      and postoperative outcome are less consistent, but there is emerging evidence
      suggesting that seizures are less likely to remit with surgery when presurgical
      abnormalities are observed in the connectivity supporting brain regions serving
      as network nodes located outside the resected temporal lobe. Future work,
      possibly harnessing the potential from multimodal imaging approaches, may further
      elucidate the etiology of persistent postoperative seizures in patients with
      refractory TLE. Furthermore, quantitative imaging techniques may be explored to
      provide individualized measures of postoperative seizure freedom outcome. 

PMID- 25853083
TI  - What does diffusion tensor imaging (DTI) tell us about cognitive networks in
      temporal lobe epilepsy?
AB  - Diffusion tensor imaging (DTI) has provided considerable insight into our
      understanding of epilepsy as a network disorder, revealing subtle alterations in
      white matter microstructure both proximal and distal to the epileptic focus.
      These white matter changes have been shown to assist with lateralizing the
      seizure focus, as well as delineating the location/anatomy of key white matter
      tracts (i.e., optic radiations) for surgical planning. However, only recently
      have studies emerged describing the utility of DTI for probing cognitive networks
      in patients with epilepsy and for examining the structural plasticity within
      these networks both before and after epilepsy surgery. Here, we review the
      current literature describing the use of DTI for understanding language and
      memory networks in patients with temporal lobe epilepsy (TLE), as well as the
      extant literature on networks associated with executive functioning and global
      intelligence. Studies of memory and language reveal a complex network of
      frontotemporal fibers that contribute to naming and fluency performance in TLE,
      and demonstrate that these networks appear to undergo adaptive changes in
      response to surgical intervention. Although studies of executive functioning and
      global intelligence have been less conclusive, there is accumulating evidence
      that aberrant communication between frontoparietal and medial temporal networks
      may underlie working memory impairment in TLE. More recently, multimodal imaging
      studies have provided evidence that disruptions within these white matter
      networks co-localize with functional changes observed on functional MRI. However,
      structure-function associations are not entirely coherent and may breakdown in
      patients with TLE, especially those with a left-sided seizure focus. Although the
      reasons for discordant findings are unclear, small sample sizes, heterogeneity
      within patient populations and limitations of the current tensor model may
      account for contradictory and null findings. Improvements in imaging hardware and
      higher field strengths have now paved the way for the implementation of advanced
      diffusion techniques, and these advanced models show great promise for improving
      our understanding of how network dysfunction contributes to cognitive morbidity
      in TLE. 

PMID- 25853085
TI  - The potential role of novel diffusion imaging techniques in the understanding and
      treatment of epilepsy.
AB  - Epilepsy is a common neurological disorder in which magnetic resonance imaging
      plays a key role. Diffusion imaging based on the molecular diffusion of water has
      been widely used clinically and in research for patients with epilepsy. Diffusion
      tensor imaging (DTI), the most common model, has been used for around two
      decades. Several parameters can be derived from DTI that are sensitive, but non
      specific, to underlying structural changes. DTI assumes a single diffusion
      process following a Gaussian distribution within each voxel and is thus an overly
      simplistic representation of tissue microstructure. Several more advanced models
      of diffusion are now available that may have greater utility in the understanding
      of the effects of epilepsy on tissue microstructure. In this review, I summarise
      the principles, applications in epilepsy and future potential of three such
      techniques. Diffusion kurtosis imaging (DKI) characterises the degree to which
      diffusion deviates from Gaussian behaviour and gives an idea of the underlying
      tissue complexity. It has been used in both focal and generalised epilepsy and
      seems more sensitive than DTI. Multi-compartment models separate the signal from
      extra- and intra-axonal compartments in each voxel. The Composite Hindered and
      Restricted Model of Diffusion (CHARMED) can characterise axonal density but has
      not yet been applied in patients with epilepsy. The Neurite Orientation
      Dispersion and Density Imaging (NODDI) model can determine the intracellular
      volume fraction (ICVF) and degree of dispersion of neurite orientation.
      Preliminary data suggest it may more sensitive than conventional and diffusion
      imaging in localising focal epilepsy. 

PMID- 25853086
TI  - Strengths and limitations of tractography methods to identify the optic radiation
      for epilepsy surgery.
AB  - Diffusion tensor imaging (DTI) tractography (TG) can visualize Meyer's loop (ML),
      providing important information for the epilepsy surgery team, both for
      preoperative counseling and to reduce the frequency of visual field defects after
      temporal lobe resection (TLR). This review highlights significant steps in the TG
      process, specifically the processing of raw data including choice of TG algorithm
      and the interpretation and validation of results. A lack of standardization of TG
      of the optic radiation makes study comparisons challenging. We discuss results
      showing differences between studies and uncertainties large enough to be of
      clinical relevance and present implications of this technique for temporal lobe
      epilepsy surgery. Recent studies in temporal lobe epilepsy patients, employing TG
      intraoperatively, show promising results in reduction of visual field defects,
      with maintained seizure reduction. 

PMID- 25853084
TI  - White matter in temporal lobe epilepsy: clinico-pathological correlates of water
      diffusion abnormalities.
AB  - Using magnetic resonance imaging, it is possible to measure the behavior of
      diffusing water molecules, and the metrics derived can be used as indirect
      markers of tissue micro-architectural properties. Numerous reports have
      demonstrated that patients with temporal lobe epilepsy (TLE) have water diffusion
      abnormalities in several white matter structures located within and beyond the
      epileptogenic temporal lobe, showing that TLE is not a focal disorder, but rather
      a brain network disease. Differences in severity and spatial extent between
      patients with or without mesial temporal sclerosis (MTS), as well as differences
      related to hemispheric seizure onset, are suggestive of different
      pathophysiological mechanisms behind different forms of TLE, which in turn result
      in specific cognitive disabilities. The biological interpretation of diffusion
      abnormalities is based on a wealth of information from animal models of white
      matter damage, and is supported by recent reports that directly correlate
      diffusion metrics with histological characteristics of surgical specimens of TLE
      patients. Thus, there is now more evidence showing that the increased mean
      diffusivity (MD) and concomitant reductions of diffusion anisotropy that are
      frequently observed in several white matter bundles in TLE patients reflect
      reduced axonal density (increased extra-axonal space) due to smaller-caliber
      axons, and abnormalities in the myelin sheaths of the remaining axons. Whether
      these histological and diffusion features are a predisposing factor for epilepsy
      or secondary to seizures is still uncertain; some reports suggest the latter.
      This article summarizes recent findings in this field and provides a synopsis of
      the histological features seen most frequently in post-surgical specimens of TLE
      patients in an effort to aid the interpretation of white matter diffusion
      abnormalities. 

PMID- 25853089
TI  - Modeling cytomegalovirus infection in mouse tumor models.
AB  - The hypothesis that cytomegalovirus (CMV) modulates cancer is evolving.
      Originally discovered in glioblastoma in 2002, the number of cancers, where
      intratumoral CMV antigen is detected, has increased in recent years suggesting
      that CMV actively affects the pathobiology of certain tumors. These findings are
      controversial as several groups have also reported inability to replicate these
      results. Regardless, several clinical trials for glioblastoma are underway or
      have been completed that target intratumoral CMV with anti-viral drugs or
      immunotherapy. Therefore, a better understanding of the possible pathobiology of
      CMV in cancer needs to be ascertained. We have developed genetic, syngeneic, and
      orthotopic malignant glioma mouse models to study the role of CMV in cancer
      development and progression. These models recapitulate for the most part
      intratumoral CMV expression as seen in human tumors. Additionally, we discovered
      that CMV infection in Trp53(-/+) mice promotes pleomorphic rhabdomyosarcomas.
      These mouse models are not only a vehicle for studying pathobiology of the viral
      tumor interaction but also a platform for developing and testing cancer
      therapeutics. 

PMID- 25853087
TI  - Methods and utility of EEG-fMRI in epilepsy.
AB  - Brain activity data in general and more specifically in epilepsy can be
      represented as a matrix that includes measures of electrophysiology, anatomy and
      behaviour. Each of these sub-matrices has a complex interaction depending upon
      the brain state i.e., rest, cognition, seizures and interictal periods. This
      interaction presents significant challenges for interpretation but also potential
      for developing further insights into individual event types. Successful
      treatments in epilepsy hinge on unravelling these complexities, and also on the
      sensitivity and specificity of methods that characterize the nature and
      localization of underlying physiological and pathological networks. Limitations
      of pharmacological and surgical treatments call for refinement and elaboration of
      methods to improve our capability to localise the generators of seizure activity
      and our understanding of the neurobiology of epilepsy. Simultaneous
      electroencephalography and functional magnetic resonance imaging (EEG-fMRI), by
      potentially circumventing some of the limitations of EEG in terms of sensitivity,
      can allow the mapping of haemodynamic networks over the entire brain related to
      specific spontaneous and triggered epileptic events in humans, and thereby
      provide new localising information. In this work we review the published
      literature, and discuss the methods and utility of EEG-fMRI in localising the
      generators of epileptic activity. We draw on our experience and that of other
      groups, to summarise the spectrum of information provided by an increasing number
      of EEG-fMRI case-series, case studies and group studies in patients with
      epilepsy, for its potential role to elucidate epileptic generators and networks.
      We conclude that EEG-fMRI provides a multidimensional view that contributes
      valuable clinical information to localize the epileptic focus with potential
      important implications for the surgical treatment of some patients with drug
      resistant epilepsy, and insights into the resting state and cognitive network
      dynamics. 

PMID- 25853088
TI  - Utility of magnetic resonance spectroscopic imaging for human epilepsy.
AB  - This review discusses the potential utility of broad based use of magnetic
      resonance (MR) spectroscopic imaging for human epilepsy and seizure localization.
      The clinical challenges are well known to the epilepsy community, intrinsic in
      the variability of location, volumetric size and network extent of epileptogenic
      tissue in individual patients. The technical challenges are also evident, with
      high performance requirements in multiple steps, including magnet homogeneity,
      detector performance, sequence design, speed of acquisition in addition to large
      territory spectral processing. We consider how MR spectroscopy and spectroscopic
      imaging has been informative for epilepsy thus far, with specific attention to
      what is measured, the interpretation of such measurements and technical
      performance challenges. Examples are shown from medial temporal lobe and
      neocortical epilepsies are considered from 4T, 7T and most recently 3T. 

PMID- 25853090
TI  - Hereditary cancer risk assessment: challenges for the next-gen sequencing era.

PMID- 25853091
TI  - Cancer-associated fibroblasts connect metastasis-promoting communication in
      colorectal cancer.
AB  - Colorectal cancer (CRC) progression and eventually metastasis is directed in many
      aspects by a circuitous ecosystem consisting of an extracellular matrix scaffold
      populated by cancer-associated fibroblasts (CAFs), endothelial cells, and diverse
      immune cells. CAFs are recruited from local tissue-resident fibroblasts or
      pericryptal fibroblasts and distant fibroblast precursors. CAFs are highly
      abundant in CRC. In this review, we apply the metastasis-promoting communication
      of colorectal CAFs to 10 cancer hallmarks described by Hanahan and Weinberg. CAFs
      influence innate and adaptive tumor immune responses. Using datasets from
      previously published work, we re-explore the potential messages implicated in
      this process. Fibroblasts present in metastasis (metastasis-associated
      fibroblasts) from CRC may have other characteristics and functional roles than
      CAFs in the primary tumor. Since CAFs connect metastasis-promoting communication,
      CAF markers are potential prognostic biomarkers. CAFs and their products are
      possible targets for novel therapeutic strategies. 

PMID- 25853092
TI  - Image-guided radiotherapy and -brachytherapy for cervical cancer.
AB  - Conventional radiotherapy for cervical cancer relies on clinical examination, 3
      dimensional conformal radiotherapy (3D-CRT), and 2-dimensional intracavitary
      brachytherapy. Excellent local control and survival have been obtained for small
      early stage cervical cancer with definitive radiotherapy. For bulky and locally
      advanced disease, the addition of chemotherapy has improved the prognosis but
      toxicity remains significant. New imaging technology such as positron-emission
      tomography and magnetic resonance imaging has improved tumor delineation for
      radiotherapy planning. Image-guided radiotherapy (IGRT) may decrease treatment
      toxicity of whole pelvic radiation because of its potential for bone marrow,
      bowel, and bladder sparring. Tumor shrinkage during whole pelvic IGRT may
      optimize image-guided brachytherapy (IGBT), allowing for better local control and
      reduced toxicity for patients with cervical cancer. IGRT and IGBT should be
      integrated in future prospective studies for cervical cancer. 

PMID- 25853093
TI  - Stereotactic ablative radiosurgery for locally advanced or recurrent skull base
      malignancies with prior external beam radiation therapy.
AB  - PURPOSE: Stereotactic ablative radiotherapy (SABR) is an attractive modality to
      treat malignancies invading the skull base as it can deliver a highly conformal
      dose with minimal toxicity. However, variation exists in the prescribed dose and
      fractionation. The purpose of our study is to examine the local control,
      survival, and toxicities in SABR for the treatment of previously irradiated
      malignant skull base tumors. MATERIALS AND METHODS: A total of 31 patients and 40
      locally advanced or recurrent head and neck malignancies involving the skull base
      treated with a common SABR regimen, which delivers a radiation dose of 44 Gy in 5
      fractions from January 1st, 2004 to December 31st, 2013, were retrospectively
      reviewed. The local control rate (LC), progression-free survival rate, overall
      survival (OS) rate, and toxicities were reported. RESULTS: The median follow-up
      time of all patients was 11.4 months (range: 0.6-67.2 months). The median tumor
      volume was 27 cm(3) (range: 2.4-205 cm(3)). All patients received prior external
      beam radiation therapy with a median radiation dose of 64 Gy (range: 24-75.6 Gy)
      delivered in 12-42 fractions. Twenty patients had surgeries prior to SABR.
      Nineteen patients received chemotherapy. Specifically, eight patients received
      concurrent cetuximab (ErbituxTM) with SABR. The median time-to-progression (TTP)
      was 3.3 months (range: 0-16.9 months). For the 29 patients (93.5%) who died, the
      median time from the end of first SABR to death was 10.3 months (range: 0.5-41.4
      months). The estimated 1-year OS rate was 35%. The estimated 2-year OS rate was
      12%. Treatment was well-tolerated without grade 4 or 5 treatment-related
      toxicities. CONCLUSION: Stereotactic ablative radiotherapy has been shown to
      achieve low toxicities in locally advanced or recurrent, previously irradiated
      head and neck malignancies invading the skull base.

PMID- 25853094
TI  - Cardiovascular toxicities of breast cancer treatment: emerging issues in cardio
      oncology.

PMID- 25853095
TI  - Correlation of hemorrhage, axonal damage, and blood-tissue barrier disruption in
      brain and retina of Malawian children with fatal cerebral malaria.
AB  - BACKGROUND: The retinal and brain histopathological findings in children who died
      from cerebral malaria (CM) have been recently described. Similar changes occur in
      both structures, but the findings have not been directly compared in the same
      patients. In this study, we compared clinical retinal findings and retinal and
      cerebral histopathological changes in a series of patients in Blantyre, Malawi,
      who died of CM. METHODS: The features systematically compared in the same patient
      were: (1) clinical, gross and microscopic retinal hemorrhages with microscopic
      cerebral hemorrhages, (2) retinal and cerebral hemorrhage-associated and 
      unassociated axonal damage, and fibrinogen leakage, and (3) differences in the
      above features between the pathological categories of CM without microvascular
      pathology (CM1) and CM with microvascular pathology (CM2) in retina and brain.
      RESULTS: Forty-seven patients were included: seven CM1, 28 CM2, and 12 controls.
      In the 35 malaria cases retinal and cerebral pathology correlated in all features
      except for non-hemorrhage associated fibrinogen leakage. Regarding CM1 and CM2
      cases, the only differences were in the proportion of patients with hemorrhage
      associated cerebral pathology, and this was expected, based on the definitions of
      CM1 and CM2. The retina did not show this difference. Non-hemorrhage associated
      pathology was similar for the two groups. COMMENT: As postulated,
      histopathological features of hemorrhages, axonal damage and non-hemorrhage
      associated fibrinogen leakage correlated in the retina and brain of individual
      patients, although the difference in hemorrhages between the CM1 and CM2 groups
      was not consistently observed in the retina. These results help to underpin the
      utility of ophthalmoscopic examination and fundus findings to help in diagnosis
      and assessment of cerebral malaria patients, but may not help in distinguishing
      between CM1 and CM2 patients during life.

PMID- 25853097
TI  - Correction.
AB  - [This corrects the article DOI: 10.7860/JCDR/2014/9827.5191.]. 

PMID- 25853098
TI  - Primary cancer prevention by green tea, and tertiary cancer prevention by the
      combination of green tea catechins and anticancer compounds.
AB  - Green tea is a daily beverage, a non-oxidized non-fermented product containing at
      least four green tea catechins. Considering our first results when repeated
      applications of (-)-epigallocatechin gallate (EGCG) prevented tumor promotion in
      mouse skin, we have continued to look at green tea as a possible cancer
      preventive agent. 1) The 10-year prospective cohort study by Drs. K. Nakachi and
      K. Imai revealed that drinking 10 Japanese-size cups (120 mL/cup) of green tea
      per day delayed cancer onset in humans by 7.3 years among females and by 3.2
      years among males. The delay of cancer onset is of course significant evidence of
      primary cancer prevention in humans. 2) In collaboration with Dr. H. Moriwaki's
      group we successfully presented a prototype of tertiary cancer prevention showing
      that 10 Japanese-size cups of green tea daily, supplemented with tablets of green
      tea extract (G.T.E), reduced recurrence of colorectal adenomas in polypectomy
      patients by 51.6% (from 31% to 15%). 3) In 1999, we first reported that the
      combination of green tea catechins and non-steroidal anti-inflammatory drugs
      showed synergistic anticancer effects in both in vitro and in vivo experiments,
      along with elucidation of the mechanism. 4) Further studies by other
      investigators have revealed that various combinations of EGCG or green tea
      extract and anticancer compounds inhibit tumor volume in xenograft mouse models
      implanted with various human cancer cell lines. Green tea is a cancer preventive,
      and green tea catechins act as synergists with anticancer compounds. 

PMID- 25853096
TI  - Approaches to treatment of emerging Shiga toxin-producing Escherichia coli
      infections highlighting the O104:H4 serotype.
AB  - Shiga toxin-producing Escherichia coli (STEC) are a group of diarrheagenic
      bacteria associated with foodborne outbreaks. Infection with these agents may
      result in grave sequelae that include fatality. A large number of STEC serotypes
      has been identified to date. E. coli serotype O104:H4 is an emerging pathogen
      responsible for a 2011 outbreak in Europe that resulted in over 4000 infections
      and 50 deaths. STEC pathogenicity is highly reliant on the production of one or
      more Shiga toxins that can inhibit protein synthesis in host cells resulting in a
      cytotoxicity that may affect various organ systems. Antimicrobials are usually
      avoided in the treatment of STEC infections since they are believed to induce
      bacterial cell lysis and the release of stored toxins. Some antimicrobials have
      also been reported to enhance toxin synthesis and production from these
      organisms. Various groups have attempted alternative treatment approaches
      including the administration of toxin-directed antibodies, toxin-adsorbing
      polymers, probiotic agents and natural remedies. The utility of antibiotics in
      treating STEC infections has also been reconsidered in recent years with certain
      modalities showing promise. 

PMID- 25853099
TI  - Small Molecule Inhibitors to Disrupt Protein-protein Interactions of Heat Shock
      Protein 90 Chaperone Machinery.
AB  - Heat shock protein 90 (Hsp90) is an adenosine triphosphate dependent molecular
      chaperone in eukaryotic cells that regulates the activation and maintenance of
      numerous regulatory and signaling proteins including epidermal growth factor
      receptor, human epidermal growth factor receptor 2, mesenchymal-epithelial
      transition factor, cyclin-dependent kinase-4, protein kinase B, hypoxia-inducible
      factor 1alpha, and matrix metalloproteinase-2. Since many of Hsp90 clients are
      oncogenic proteins, Hsp90 has become an attractive therapeutic target for
      treatment of cancer. To discover small molecule inhibitors targeting Hsp90
      chaperone machinery, several strategies have been employed, which results in
      three classes of inhibitors such as N-terminal inhibitors, C-terminal inhibitors,
      and inhibitors disrupting protein-protein interactions of Hsp90 chaperone
      machinery. Developing small molecule inhibitors that modulate protein-protein
      interactions of Hsp90 is a challenging task, although it offers many alternative
      opportunities for therapeutic intervention. The lack of well-defined binding
      pocket and starting points for drug design challenges medicinal chemists to
      discover small molecule inhibitors disrupting protein-protein interactions of
      Hsp90. The present review will focus on the current studies on small molecule
      inhibitors disrupting protein-protein interactions of Hsp90 chaperone machinery,
      provide biological background on the structure, function and mechanism of Hsp90's
      protein-protein interactions, and discuss the challenges and promise of its small
      molecule modulations. 

PMID- 25853100
TI  - Endocrine-disrupting Chemicals: Review of Toxicological Mechanisms Using
      Molecular Pathway Analysis.
AB  - Endocrine disruptors are known to cause harmful effects to human through various
      exposure routes. These chemicals mainly appear to interfere with the endocrine or
      hormone systems. As importantly, numerous studies have demonstrated that the
      accumulation of endocrine disruptors can induce fatal disorders including obesity
      and cancer. Using diverse biological tools, the potential molecular mechanisms
      related with these diseases by exposure of endocrine disruptors. Recently,
      pathway analysis, a bioinformatics tool, is being widely used to predict the
      potential mechanism or biological network of certain chemicals. In this review,
      we initially summarize the major molecular mechanisms involved in the induction
      of the above mentioned diseases by endocrine disruptors. Additionally, we provide
      the potential markers and signaling mechanisms discovered via pathway analysis
      under exposure to representative endocrine disruptors, bisphenol,
      diethylhexylphthalate, and nonylphenol. The review emphasizes the importance of
      pathway analysis using bioinformatics to finding the specific mechanisms of toxic
      chemicals, including endocrine disruptors. 

PMID- 25853102
TI  - Carnosic Acid Inhibits Lipid Accumulation in 3T3-L1 Adipocytes Through
      Attenuation of Fatty Acid Desaturation.
AB  - BACKGROUND: Excess body fat accumulation contributes to the development of
      metabolic disorders that can cause adverse health effects. Carnosic acid (CA), a
      major bioactive component of rosemary (Rosemarinus officinalis), has been
      suggested to possess anti-adipogenic properties. The present study was conducted
      to elucidate the mechanism underlying the anti-adipogenic effects of CA. METHODS:
      3T3-L1 pre-adipocytes were treated with CA (0.1, 1, and 10 MUM) from day 0 to day
      8 of differentiation. On day 8, biochemical markers of lipid accumulation and the
      degree of fatty acid desaturation were measured. RESULTS: Oil Red O staining
      results, triglyceride (TG) accumulation, and glycerol 3-phosphate dehydrogenase
      activity suggested that CA significantly inhibited lipid accumulation in 3T3-L1
      adipocytes. CA significantly decreased mRNA expression of peroxisome proliferator
      activated receptor-gamma, sterol regulatory element-binding protein 1, and
      CCAAT/enhancer binding protein-alpha in a dose-dependent manner. Moreover, it
      decreased the ratio of both C16:1/C16:0 and C18:1/C18:0, with reduced expression
      of stearoyl CoA desaturase 1 mRNA and protein. CONCLUSIONS: These results suggest
      that CA efficiently suppressed adipogenesis in 3T3-L1 adipocytes and its action,
      at least in part, is associated with the downregulation of adipogenesis-related
      genes and the fatty acid composition of TG accumulated in adipocytes.

PMID- 25853101
TI  - Review of atrophic gastritis and intestinal metaplasia as a premalignant lesion
      of gastric cancer.
AB  - Atrophic gastritis (AG) and intestinal metaplasia (IM) are the main precursor
      lesions of gastric cancer as the incidence of gastric cancer increases in the
      gastric mucosa involved with AG and IM. The prevalence of AG and IM vary
      depending on countries, even it represents diverse results in the same nation.
      Usually AG is antecedent of IM but the etiologies of AG and IM are not always the
      same. The sensitivity and specificity of diagnostic methods to detect AG and IM
      are different. Furthermore, the management strategy of AG and IM has not been
      established, yet. Helicobacter pylori infection has been proved as the most
      important cause of AG and IM. Thus the eradication of H. pylori is very important
      to prevent the progression to gastric cancer which is still placed in the high
      rank in morbidity and mortality among cancers. However, the reversibility of AG
      and IM by eradication of H. pylori which was assumed to be certain by meta
      analysis is; however, controversial now. Therefore, the understanding and early
      diagnosis of AG and IM are very important, especially, in high incidence area of
      gastric cancer such as Republic of Korea. 

PMID- 25853103
TI  - Anthocyanins From the Fruit of Vitis coignetiae Pulliat Potentiate the Cisplatin
      Activity by Inhibiting PI3K/Akt Signaling Pathways in Human Gastric Cancer Cells.
AB  - BACKGROUND: Cisplatin (cis-diaminedichloroplatinum, CDDP) is a widely used
      chemotherapeutic agent for the treatment of many cancers. However, initial
      resistance to CDDP is a serious problem in treating these cancers. Vitis
      coignetiae Pulliat (Meoru in Korea) have shown anti-nuclear factor kappa B and
      anti-epidermal growth factor receptor activities in cancer cells. METHODS: In
      this study, in order to seeking an approach to increase the anti-cancer effects
      of CDDP with natural products. Here, we investigated anthocyanins isolated from
      Vitis coignetiae Pulliat (anthocyanidins isolated from meoru, AIMs) can enhance
      anti-cancer effects of cisplatin (CDDP) in stomach cancer cells. The cell
      viability of SNU-1 and SNU-16 cells after treated with AIMs and CDDP were
      analyzed by MTT assay. The expressions of Akt and X-linked inhibitor of apoptosis
      protein (XIAP) proteins were examined by western blot in AIMs- and CDDP-treated
      cells. RESULTS: We found that AIMs enhanced anticancer effects of CDDP, which
      activity was additive but not synergistic. AIMs suppressed Akt activity of the
      cancer cells activated by CDDP. AIMs also suppressed in XIAP an anti-apoptotic
      protein. CONCLUSIONS: This study suggests that the anthocyanins isolated from
      fruits of Vitis coignetiae Pulliat enhanced anti-cancer effects of CDDP by
      inhibiting Akt activity activated by CDDP.

PMID- 25853104
TI  - Inhibition of Ubiquitin-specific Peptidase 8 Suppresses Growth of Gefitinib
      resistant Non-small Cell Lung Cancer Cells by Inducing Apoptosis.
AB  - BACKGROUND: Therapeutic approach by treatment with epidermal growth factor
      receptor-tyrosine kinase inhibitors (EGFR-TKIs) like gefitinib or erlotinib to
      non-small cell lung cancer (NSCLC) patients has been limited due to emergence of
      acquired drug resistance. Our study was aimed to investigate whether the
      inhibition of ubiquitin-specific peptidase 8 (USP8) could be an alternative
      strategy capable of overcoming acquired resistance to EGFR-TKIs for treatment of
      NSCLCs. METHODS: The anticancer effect of USP8 inhibitor was determined by
      testing anchorage-dependent or independent growth of gefitinib-sensitive or
      resistant NSCLCs. The immunoprecipitation and western blotting were conducted to
      check molecular interaction and signaling pathway followed by USP8 inhibition.
      RESULTS: Inhibition of USP8 induced overall degradation of oncogenic receptor
      tyrosine kinases including EGFR and Met, leading to a suppression of anchorage
      dependent or independent cell growth of gefitinib-sensitive or resistant NSCLCs.
      Also, treatment with the USP8 inhibitor markedly induced apoptosis in HCC827GR
      cells. Notably, treatment with the USP8 inhibitor was more effective in
      suppressing cell growth and inducing apoptosis in gefitinib-resistant HCC827GR
      cells than that of gefitinib-sensitive HCC827 cells. CONCLUSIONS: Inhibition of
      USP8 could be an effective strategy for overcoming gefitinib resistance in
      NSCLCs.

PMID- 25853105
TI  - A Controlled, Randomized, Double-blind Trial to Evaluate the Effect of Vegetables
      and Whole Grain Powder That Is Rich in Dietary Fibers on Bowel Functions and
      Defecation in Constipated Young Adults.
AB  - BACKGROUND: This study evaluated the effect of vege-powder (VP), mainly consisted
      of chicory, broccoli, and whole grains, on bowel habit improvement and
      constipation alleviation. METHODS: Using the Roman standard II, 96 male and
      female subjects in their twenties with constipation symptoms were divided into a
      control group or VP group. Subjects in a control group were supplied with rice
      flakes-powder (RFP) and subjects in the VP group were provided with 30 g of VP
      twice daily for 4 weeks. Constipation relief effectiveness was surveyed on 5
      point Likert scales depending on stool hardness, amount of stool, sensation of
      incomplete evacuation, and straining to defecate at day 0, 14, and 28 of RFP or
      VP intake. RESULTS: Repeated measures analysis of variance analysis revealed that
      VP intake caused significant temporal changes in stool hardness, amount,
      sensation of incomplete evacuation, and straining to defecate. In addition,
      significant differences between control and VP groups were found in stool
      hardness, amount, sensation of incomplete evacuation, and straining to defecate
      at day 14 and 28 of experimental diet consumption. VP supplement for 2 weeks
      significantly increased the evacuation frequency (1.04 +/- 0.71), compared to
      control group (0.41 +/- 0.64) and this increase was maintained at 4 week of diet
      supplements. CONCLUSIONS: This result showed that constipated subjects who
      consumed VP, mainly consisting of chicory, broccoli, and whole grains, improved
      constipation symptoms at 2 and 4 weeks of consumption compared to those of
      control group who were provided with RFP.

PMID- 25853106
TI  - Clinical Implication of p16, Ki-67, and Proliferating Cell Nuclear Antigen
      Expression in Cervical Neoplasia: Improvement of Diagnostic Accuracy for High
      grade Squamous Intraepithelial Lesion and Prediction of Resection Margin
      Involvement on Conization Specimen.
AB  - BACKGROUND: Cervical intraepithelial neoplasia (CIN) grading is subjective and
      affected by substantial rates of discordance among pathologists. Although the use
      of p16INK4a (p16) staining has been proven to improve diagnostic accuracy for
      high-grade squamous intraepithelial lesion (HSIL), the clinical evidence for use
      of Ki-67 and proliferating cell nuclear antigen (PCNA) is insufficient to make an
      independent recommendation for use, alone or in combination. The primary
      objective was to evaluate clinical utility of Ki-67 and PCNA in combination with
      p16 in diagnosing HSIL. Also, we assessed the correlation between expressions of
      three biomarkers and resection margin status of conization specimen. METHODS: The
      expressions of p16, Ki-67, and PCNA were evaluated by immunohistochemical methods
      in 149 cervical tissues encompassing 17 negative lesion, 31 CIN 1, 25 CIN 2, 41
      CIN 3, and 35 invasive squamous cell carcinoma. The immunohistochemical staining
      results were classified into four grades: 0, 1+, 2+ and 3+. RESULTS: The
      expression of three biomarkers was positively associated with CIN grade. Ki-67
      immunostaining did not increase the accuracy of HSIL diagnosis when combined with
      p16 immunostaining compared with p16 immunostaining alone. In contrast, combining
      the staining results for p16 and PCNA (p16 = 3+ and PCNA >=2+) increased its
      specificity (66.7% vs. 75.0%, P = 0.031) without decrease of its sensitivity
      (98.7% vs. 98.7%) for diagnosis of CIN 3 and more sever lesion. Subgroup analysis
      for conization specimen with CIN 2 and CIN 3 showed that positive Ki-67
      immunostaining was an independent risk factor for predicting resection margin
      positivity (odds ratio = 6.52, 95% confidence interval 1.07-39.64). CONCLUSIONS:
      We found that the combined use of p16 and PCNA immunostaining enhanced diagnostic
      accuracy for HSIL. Positive Ki-67 immunostaining was associated with incomplete
      excision.

PMID- 25853107
TI  - Identification of a new selective chemical inhibitor of mutant isocitrate
      dehydrogenase-1.
AB  - BACKGROUND: Recent genome-wide sequencing studies have identified unexpected
      genetic alterations in cancer. In particular, missense mutations in isocitrate
      dehydrogenase-1 (IDH1) at arginine 132, mostly substituted into histidine (IDH1
      R132H) were observed to frequently occur in glioma patients. METHODS: We have
      purified recombinant IDH1 and IDH1-R132H proteins and monitored their catalytic
      activities. In parallel experiments, we have attempted to find new selective IDH1
      R132H chemical inhibitor(s) from a fragment-based chemical library. RESULTS: We
      have found that IDH1, but not IDH1-R132H, can catalyze the conversion of
      isocitrate into alpha-ketoglutarate (alpha-KG). In addition, we have observed
      that IDH1-R132H was more efficient than IDH1 in converting alpha-KG into (R)-2
      hydroxyglutarate (R-2HG). Moreover, we have identified a new hit molecule, e.g.,
      2-(3-trifluoromethylphenyl)isothioazol-3(2H)-one as a new selective IDH1-R132H
      inhibitor. CONCLUSIONS: We have observed an underlying biochemical mechanism
      explaining how a heterozygous IDH1 mutation contributes to the generation of R
      2HG and increases cellular histone H3 trimethylation levels. We have also
      identified a novel selective IDH1-R132H chemical hit molecule, e.g., 2-(3
      trifluoromethylphenyl)isothioazol-3(2H)-one, which could be used for a future
      lead development against IDH1-R132H.

PMID- 25853108
TI  - Do the Benefits of Male Circumcision Outweigh the Risks? A Critique of the
      Proposed CDC Guidelines.
AB  - The Centers for Disease Control and Prevention (CDC) have announced a set of
      provisional guidelines concerning male circumcision, in which they suggest that
      the benefits of the surgery outweigh the risks. I offer a critique of the CDC
      position. Among other concerns, I suggest that the CDC relies more heavily than
      is warranted on studies from Sub-Saharan Africa that neither translate well to
      North American populations nor to circumcisions performed before an age of sexual
      debut; that it employs an inadequate conception of risk in its benefit vs. risk
      analysis; that it fails to consider the anatomy and functions of the penile
      prepuce (i.e., the part of the penis that is removed by circumcision); that it
      underestimates the adverse consequences associated with circumcision by focusing
      on short-term surgical complications rather than long-term harms; that it
      portrays both the risks and benefits of circumcision in a misleading manner,
      thereby undermining the possibility of obtaining informed consent; that it
      evinces a superficial and selective analysis of the literature on sexual outcomes
      associated with circumcision; and that it gives less attention than is desirable
      to ethical issues surrounding autonomy and bodily integrity. I conclude that
      circumcision before an age of consent is not an appropriate health-promotion
      strategy. 

PMID- 25853109
TI  - Atresia of the aortic arch in 4-year-old child: a clinical case study.
AB  - Atresia of the aortic arch is a rare congenital heart defect with a high
      mortality when associated with other intracardiac defects. Cardiac magnetic
      resonance (CMR) provides the exact anatomy of the aortic arch and collateral
      circulation and is useful to diagnose-associated aortic arch anomalies. This
      report describes the case of a 4-year-old child with atresia of the aortic arch,
      referred to our institution with the diagnosis of aortic coarctation and bicuspid
      aortic valve. On clinical exam, the femoral pulses were not palpable and there
      was a significant differential blood pressure between the upper and lower limbs.
      The echocardiography showed a severely stenotic bicuspid aortic valve but was
      limited for the exact description of the aortic arch. CMR showed absence of lumen
      continuity between the ascending and descending aorta distal to the left
      subclavian artery, extending over 5 mm, with the presence of a bend in the arch
      and diverticulum on either side of the zone of discontinuity, suggesting the
      diagnosis atresia of the aortic arch rather than coarctation or interruption. The
      patient benefited from a successful surgical commissurotomy of the aortic valve
      and reconstruction of the aortic arch with a homograft. The post-operative CMR
      confirmed the good surgical result. This case emphasizes the utility of CMR to
      provide good anatomical information to establish the exact diagnosis and the
      operative strategy. 

PMID- 25853110
TI  - Closed catheter access system implementation in reducing the bloodstream
      infection rate in low birth weight preterm infants.
AB  - BACKGROUND: Bloodstream infection (BSI) is one of the significant causes of
      morbidity and mortality encountered in a neonatal intensive care unit, especially
      in developing countries. Despite the implementation of infection control
      practices, such as strict hand hygiene, the BSI rate in our hospital is still
      high. The use of a closed catheter access system to reduce BSI related to
      intravascular catheter has hitherto never been evaluated in our hospital.
      OBJECTIVE: To determine the effects of closed catheter access system
      implementation in reducing the BSI rate in preterm neonates with low birth
      weight. METHODS: Randomized clinical trial was conducted on 60 low birth weight
      preterm infants hospitalized in the neonatal unit at Cipto Mangunkusumo Hospital,
      Jakarta, Indonesia from June to September 2013. Randomized subjects either
      received a closed or non-closed catheter access system. Subjects were monitored
      for 2 weeks for the development of BSI based on clinical signs, abnormal
      infection parameters, and blood culture. RESULTS: Closed catheter access system
      implementation gave a protective effect toward the occurrence of culture-proven
      BSI (relative risk 0.095, 95% CI 0.011-0.85, p = 0.026). Risk of culture-proven
      BSI in the control group was 10.545 (95% CI 1.227-90.662, p = 0.026). BSI
      occurred in 75% of neonates without risk factors of infection in the control
      group compared to none in the study group. CONCLUSION: The use of a closed
      catheter access system reduced the BSI in low birth weight preterm infants.
      Choosing the right device design, proper disinfection of device, and appropriate
      frequency of connector change should be done simultaneously.

PMID- 25853112
TI  - New treatment perspectives in autism spectrum disorders.

PMID- 25853111
TI  - Should we consider alternatives to universal well-child behavioral-developmental
      screening?
AB  - The prevalence of developmental disabilities in the young age is of the order of
      15%. When behavioral and social-emotional disorders, physical impairments, and
      sensory disorders are included, the need for special intervention increases to
      one out of four children. As the sensitivity and specificity of the best
      screening tests are in the range of 70-80%, their predictive value is
      controversial. The cost of conducting definitive tests and repeat screening for
      those who fail the screening tests is high. Children with severe disorders can be
      identified clinically without a screening test. The poor predictability,
      difficulty in implementation, and the high costs of developmental testing suggest
      that children, particularly those in high-risk communities, might be better
      served by implementing intervention programs for all, instead of trying to
      identify the outliers through screening. 

PMID- 25853113
TI  - New records of mosquitoes (Diptera: culicidae) from bolivar state in South
      eastern Venezuela, with 27 new species for the state and 5 of them new in the
      country.
AB  - This is the first part of a series of studies related to mosquito ecological and
      biogeographic aspects. A total of 69 mosquito species (Diptera: Culicidae) was
      collected in 16 localities sampled in the Gran Sabana Municipality, Canaima
      National Park, and Venezuela. Twenty-seven mosquito species are recorded for the
      first time from Bolivar State, Venezuela. Five of them species are reported for
      the first time in Venezuela: Anopheles malefactor Dyar and Knab (1907); Chagasia
      bonneae Root (1927); Chagasia ablusa Harbach (2009); Culex anduzei Lane (1944),
      and Uranotaenia leucoptera Theobald (1907). Their medical importance is
      commented, and ecological and epidemiological aspects are discussed. A checklist
      of the mosquito species reported in the Gran Sabana County is given. 

PMID- 25853114
TI  - Promoting public health through state cancer control plans: a review of capacity
      and sustainability.
AB  - The Centers for Disease Prevention and Control's National Comprehensive Cancer
      Control (CCC) Program oversee CCC programs designed to develop and implement CCC
      plans via CCC coalitions, alliances, or consortia of program stakeholders. We
      reviewed 40 up-to-date plans for states and the District of Columbia in order to
      assess how capacity building and sustainability, two evidence-based practices
      necessary for organizational readiness, positive growth, and maintenance are
      addressed. We employed an electronic key word search, supplemented by full text
      reviews of each plan to complete a content analysis of the CCC plans. Capacity is
      explicitly addressed in just over half of the plans (53%), generally from a
      conceptual point of view, with few specifics as to how capacity will be developed
      or enhanced. Roles and responsibilities, timelines for action, and measurements
      for evaluation of capacity building are infrequently mentioned. Almost all (92%)
      of the 40 up-to-date plans address sustainability on at least a cursory level,
      through efforts aimed at funding or seeking funding, policy initiatives, and/or
      partnership development. However, few details as to how these strategies will be
      implemented are found in the plans. We present the Texas plan as a case study
      offering detailed insight into how one plan incorporated capacity building and
      sustainability into its development and implementation. Training, technical
      assistance, templates, and tools may help CCC coalition members address capacity
      and sustainability in future planning efforts and assure the inclusion of
      capacity building and sustainability approaches in CCC plans at the state,
      tribal, territorial, and jurisdiction levels. 

PMID- 25853115
TI  - Corrigendum: use of emerging technologies to assess differences in outdoor
      physical activity in st. Louis, missouri.
AB  - [This corrects the article on p. 41 in vol. 2, PMID: 24904908.]. 

PMID- 25853117
TI  - Additional Evaluation of the Point-of-Contact Circulating Cathodic Antigen Assay
      for Schistosoma mansoni Infection.
AB  - Studies of the urine-based point-of-contact cathodic circulating antigen test
      (POC-CCA) in Schistosoma mansoni-endemic settings in Africa indicate it has good
      sensitivity in detecting infections, but in areas of low prevalence, the POC-CCA
      can be positive for persons who are egg-negative by Kato-Katz stool assays. We
      examined the POC-CCA assay for: (a) batch-to-batch stability; (b) intra-reader
      and inter-reader variability; (c) day-to-day variability compared to Kato-Katz
      stool assays, and (d) to see if praziquantel (PZQ) treatment converted Kato-Katz
      negative/POC-CCA positive individuals to POC-CCA negativity. We found essentially
      no batch-to-batch variation, negligible intra-reader variability (2%), and
      substantial agreement for inter-reader reliability. Some day-to-day variation was
      observed over 5 days of urine collection, but less than the variation in Kato
      Katz stool assays over 3 days. To evaluate the effect of treatment on Kato-Katz(
      )/POC-CCA(+) children, 149 children in an area of 10-15% prevalence who were Kato
      Katz(-) based on 3 stool samples but POC-CCA(+) were enrolled. Seven days after
      treatment (PZQ 40 mg/kg) samples were again collected and tested. Almost half
      (47%) POC-CCA positive children turned negative. Those still POC-CCA positive
      received a second treatment, and 34% of them turned POC-CCA negative upon this
      second treatment. Most who remained POC-CCA positive shifted each time to a
      "lesser" POC-CCA "level of positivity." The data suggest that most Kato-Katz
      negative/POC-CCA positive individuals harbor low-intensity infections, and each
      treatment kills all or some of their adult worms. The data also suggest that when
      evaluated by a more sensitive assay, the effective cure rates for PZQ are
      significantly less than those inferred from fecal testing. These findings have
      public health significance for the mapping and monitoring of Schistosoma
      infections and in planning the transition from schistosomiasis morbidity control
      to elimination of transmission. 

PMID- 25853116
TI  - The Association between Depressive Symptoms and Physical Diseases in Switzerland:
      A Cross-Sectional General Population Study.
AB  - OBJECTIVE: To estimate the association between depressive symptoms and physical
      diseases in Switzerland, as respective findings might inform about future
      estimates of mental and physical health care costs. METHODS: A population-based
      study, using data from the Swiss Health Survey collected by computer-assisted
      telephone interviews and additional written questionnaires during the year 2007
      (n = 18,760) in Switzerland. The multistage stratified random sample included
      subjects aged 15 years and older, living in a private Swiss household with a
      telephone connection. Complete data were available for 14,348 subjects (51% of
      all subjects reached by telephone). Logistic regression analyses were used to
      estimate the associations between depressive symptoms and any physical disease,
      or a specific physical disease out of 13 non-communicable physical diseases
      assessed with a self-report checklist on common physical diseases. Analyses were
      adjusted for sex, age, education, occupation, and household income. RESULTS: In
      the adjusted models, depressive symptoms were associated with arthrosis and
      arthritis [Odds Ratio (OR) = 1.79, 95% confidence interval (CI) = 1.28-2.50] and
      any physical disease (OR = 1.67, 95% CI = 1.33-2.10) after controlling for
      multiple testing. CONCLUSION: Our findings contribute to a better understanding
      of the comorbidity of depressive symptoms and arthrosis and arthritis in
      Switzerland and might have implications for more precise future estimates of
      mental and physical health care costs.

PMID- 25853118
TI  - Economic Impact of Leading Prosperity Diseases: COPD in South East Europe.

PMID- 25853120
TI  - Radiation-induced formation of purine lesions in single and double stranded DNA:
      revised quantification.
AB  - The formation of oxidative lesions arising from double stranded DNA damage is of
      major significance to chemical biology from the perspective of application to
      human health. The quantification of purine lesions arising from gamma-radiation
      induced hydroxyl radicals (HO(*)) has been the subject of numerous studies, with
      discrepancies on the measured 5',8-cyclo-2'-deoxyadenosine (cdA) and 5',8-cyclo
      2'-deoxyguanosine (cdG) lesions reported by different groups. Here we applied an
      ameliorative protocol for the analysis of DNA damage with quantitative
      determination of these lesions via isotope dilution liquid chromatography coupled
      with tandem mass spectrometry. Tandem-type purine lesions were quantified along
      with 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxo-dG) and 7,8-dihydro-8-oxo-2'
      deoxyadenosine (8-oxo-dA) in single and double stranded DNA, generated during DNA
      exposure to diffusible HO(*) radicals in the absence or presence of physiological
      levels of oxygen. The cdA and cdG lesions in absence of oxygen were found ~2
      times higher in single than double stranded DNA, with 5'R being ~6.5 and ~1.5
      times more predominant than 5'S in cdG and cdA, respectively. Interestingly, in
      the presence of 5% molecular oxygen the R/S ratios are retained with
      substantially decreased yields for cdA and cdG, whereas 8-oxo-dA and 8-oxo-dG
      remain nearly constant. The overall lesion formation follows the order: 8-oxo-dG
      >> 8-oxo-dA > 5'R-cdG > 5'R-cdA > 5'S-cdA > 5'S-cdG. By this method, there was a
      conclusive evaluation of radiation-induced DNA purine lesions. 

PMID- 25853119
TI  - The elusive nature and diagnostics of misfolded Abeta oligomers.
AB  - Amyloid-beta (Abeta) peptide oligomers are believed to be the causative agents of
      Alzheimer's disease (AD). Though post-mortem examination shows that insoluble
      fibrils are deposited in the brains of AD patients in the form of intracellular
      (tangles) and extracellular (plaques) deposits, it has been observed that
      cognitive impairment is linked to synaptic dysfunction in the stages of the
      illness well before the appearance of these mature deposits. Increasing evidence
      suggests that the most toxic forms of Abeta are soluble low-oligomer ligands
      whose amounts better correlate with the extent of cognitive loss in patients than
      the amounts of fibrillar insoluble forms. Therefore, these ligands hold the key
      to a better understanding of AD prompting the search for clearer correlations
      between their structure and toxicity. The importance of such correlations and
      their diagnostic value for the early diagnosis of AD is discussed here with a
      particular emphasis on the transient nature and structural plasticity of
      misfolded Abeta oligomers. 

PMID- 25853121
TI  - Total synthesis of the putative structure of the proposed Banyasin A.
AB  - The first total synthesis of four possible isomers of a molecule possessing the
      configuration proposed for Banyasin A is described. The structure synthesized
      appears to be different from that of the natural product. 

PMID- 25853122
TI  - Unveiling the potential of novel yeast protein extracts in white wines
      clarification and stabilization.
AB  - Fining agents derived from animal and mineral sources are widely used to clarify
      and stabilize white wines. Nevertheless, health and environmental problems are
      being raised, concerning the allergenic and environmental impact of some of those
      fining products. In this study, our aim is to validate the potential of yeast
      protein extracts, obtained from an alternative and safe source, naturally present
      in wine: oenological yeasts. Three untreated white wines were used in this work
      in order to evaluate the impact of these novel yeast protein extracts (YPE) in
      terms of the wine clarification and stabilization improvement. Two separated
      fining trials were thus conducted at laboratory scale and the yeast alternatives
      were compared with reference fining agents, obtained from mineral, animal and
      vegetable origins. Our results indicate that YPE were capable to promote (i)
      brilliance/color improvement, (ii) turbidity reduction (76-89% comparing with the
      untreated wines), and (iii) production of compact and homogeneous lees (44%
      smaller volume than obtained with bentonite). Additionally, after submitting
      wines to natural and forced oxidations, YPE treatments revealed (iv) different
      forms of colloidal stabilization, by presenting comparable or superior effects
      when particularly compared to casein. Altogether, this study reveals that YPE
      represent a promising alternative for white wine fining, since they are resultant
      from a natural and more sustainable origin, at present not regarded as potential
      allergenic according to Regulation (EC) No. 1169/2011. 

PMID- 25853123
TI  - An easy microwave-assisted synthesis of C8-alkynyl adenine pyranonucleosides as
      novel cytotoxic antitumor agents.
AB  - We describe the synthesis of C8-alkynyl adenine pyranonucleosides 4, 5, and 8
      phenylethynyl-adenine (II), via Sonogashira cross-coupling reaction under
      microwave irradiation. Compounds 4e and II were less cytostatic than 5
      fluorouracil (almost an order of magnitude) against murine leukemia (L1210) and
      human cervix carcinoma (HeLa) cells, while the same compounds proved to be more
      active than 5-fluorouracil against human lymphocyte (CEM) cells. 

PMID- 25853124
TI  - A computational analysis of bone formation in the cranial vault in the mouse.
AB  - Bones of the cranial vault are formed by the differentiation of mesenchymal cells
      into osteoblasts on a surface that surrounds the brain, eventually forming
      mineralized bone. Signaling pathways causative for cell differentiation include
      the actions of extracellular proteins driven by information from genes. We assume
      that the interaction of cells and extracellular molecules, which are associated
      with cell differentiation, can be modeled using Turing's reaction-diffusion
      model, a mathematical model for pattern formation controlled by two interacting
      molecules (activator and inhibitor). In this study, we hypothesize that regions
      of high concentration of an activator develop into primary centers of
      ossification, the earliest sites of cranial vault bone. In addition to the Turing
      model, we use another diffusion equation to model a morphogen (potentially the
      same as the morphogen associated with formation of ossification centers)
      associated with bone growth. These mathematical models were solved using the
      finite volume method. The computational domain and model parameters are
      determined using a large collection of experimental data showing skull bone
      formation in mouse at different embryonic days in mice carrying disease causing
      mutations and their unaffected littermates. The results show that the relative
      locations of the five ossification centers that form in our model occur at the
      same position as those identified in experimental data. As bone grows from these
      ossification centers, sutures form between the bones. 

PMID- 25853125
TI  - Statistical approaches to detecting and analyzing tandem repeats in genomic
      sequences.
AB  - Tandem repeats (TRs) are frequently observed in genomes across all domains of
      life. Evidence suggests that some TRs are crucial for proteins with fundamental
      biological functions and can be associated with virulence, resistance, and
      infectious/neurodegenerative diseases. Genome-scale systematic studies of TRs
      have the potential to unveil core mechanisms governing TR evolution and TR roles
      in shaping genomes. However, TR-related studies are often non-trivial due to
      heterogeneous and sometimes fast evolving TR regions. In this review, we discuss
      these intricacies and their consequences. We present our recent contributions to
      computational and statistical approaches for TR significance testing, sequence
      profile-based TR annotation, TR-aware sequence alignment, phylogenetic analyses
      of TR unit number and order, and TR benchmarks. Importantly, all these methods
      explicitly rely on the evolutionary definition of a tandem repeat as a sequence
      of adjacent repeat units stemming from a common ancestor. The discussed work has
      a focus on protein TRs, yet is generally applicable to nucleic acid TRs, sharing
      similar features. 

PMID- 25853126
TI  - Microchamber device for detection of transporter activity of adherent cells.
AB  - We present a method to detect the transporter activity of intact adherent cells
      using a microchamber device. When adherent cells are seeded onto the poly-di
      methyl siloxane substrate having microchambers with openings smaller than the
      size of a cell, the cells form a confluent layer that covers the microchambers,
      creating minute, confined spaces. As substances exported across the cell membrane
      accumulate, transporter activity can be detected by observing the fluorescence
      intensity increase in the microchamber. We tested the microchamber device with
      HeLa cells over-expressing MDR1, an ATP-binding cassette transporter, and
      succeeded in detecting the transport of fluorescence-conjugated paclitaxel, the
      anti-cancer drug, at the single-cell level. 

PMID- 25853127
TI  - Heterogeneity of alkane chain length in freshwater and marine cyanobacteria.
AB  - The potential utilization of cyanobacteria for the biological production of
      alkanes represents an exceptional system for the next generation of biofuels.
      Here, we analyzed a diverse group of freshwater and marine cyanobacterial
      isolates from Indian culture collections for their ability to produce both
      alkanes and alkenes. Among the 50 cyanobacterial isolates screened, 32 isolates;
      14 freshwater and 18 marine isolates; produced predominantly alkanes. The GC
      MS/MS profiles revealed a higher percentage of pentadecane and heptadecane
      production for marine and freshwater strains, respectively. Oscillatoria species
      were found to be the highest producers of alkanes. Among the freshwater isolates,
      Oscillatoria CCC305 produced the maximum alkane level with 0.43 MUg/mg dry cell
      weight, while Oscillatoria formosa BDU30603 was the highest producer among the
      marine isolates with 0.13 MUg/mg dry cell weight. Culturing these strains under
      different media compositions showed that the alkane chain length was not
      influenced by the growth medium but was rather an inherent property of the
      strains. Analysis of the cellular fatty acid content indicated the presence of
      predominantly C16 chain length fatty acids in marine strains, while the
      proportion of C18 chain length fatty acids increased in the majority of
      freshwater strains. These results correlated with alkane chain length specificity
      of marine and freshwater isolates indicating that alkane chain lengths may be
      primarily determined by the fatty acid synthesis pathway. Moreover, the
      phylogenetic analysis showed clustering of pentadecane-producing marine strains
      that was distinct from heptadecane-producing freshwater strains strongly
      suggesting a close association between alkane chain length and the cyanobacteria
      habitat. 

PMID- 25853128
TI  - Learning to Classify Organic and Conventional Wheat - A Machine Learning Driven
      Approach Using the MeltDB 2.0 Metabolomics Analysis Platform.
AB  - We present results of our machine learning approach to the problem of classifying
      GC-MS data originating from wheat grains of different farming systems. The aim is
      to investigate the potential of learning algorithms to classify GC-MS data to be
      either from conventionally grown or from organically grown samples and
      considering different cultivars. The motivation of our work is rather obvious
      nowadays: increased demand for organic food in post-industrialized societies and
      the necessity to prove organic food authenticity. The background of our data set
      is given by up to 11 wheat cultivars that have been cultivated in both farming
      systems, organic and conventional, throughout 3 years. More than 300 GC-MS
      measurements were recorded and subsequently processed and analyzed in the MeltDB
      2.0 metabolomics analysis platform, being briefly outlined in this paper. We
      further describe how unsupervised (t-SNE, PCA) and supervised (SVM) methods can
      be applied for sample visualization and classification. Our results clearly show
      that years have most and wheat cultivars have second-most influence on the
      metabolic composition of a sample. We can also show that for a given year and
      cultivar, organic and conventional cultivation can be distinguished by machine
      learning algorithms. 

PMID- 25853129
TI  - Photosynthetic constraints on fuel from microbes.

PMID- 25853130
TI  - RobOKoD: microbial strain design for (over)production of target compounds.
AB  - Sustainable production of target compounds such as biofuels and high-value
      chemicals for pharmaceutical, agrochemical, and chemical industries is becoming
      an increasing priority given their current dependency upon diminishing
      petrochemical resources. Designing these strains is difficult, with current
      methods focusing primarily on knocking-out genes, dismissing other vital steps of
      strain design including the overexpression and dampening of genes. The design
      predictions from current methods also do not translate well-into successful
      strains in the laboratory. Here, we introduce RobOKoD (Robust, Overexpression,
      Knockout and Dampening), a method for predicting strain designs for
      overproduction of targets. The method uses flux variability analysis to profile
      each reaction within the system under differing production percentages of target
      compound and biomass. Using these profiles, reactions are identified as potential
      knockout, overexpression, or dampening targets. The identified reactions are
      ranked according to their suitability, providing flexibility in strain design for
      users. The software was tested by designing a butanol-producing Escherichia coli
      strain, and was compared against the popular OptKnock and RobustKnock methods.
      RobOKoD shows favorable design predictions, when predictions from these methods
      are compared to a successful butanol-producing experimentally-validated strain.
      Overall RobOKoD provides users with rankings of predicted beneficial genetic
      interventions with which to support optimized strain design. 

PMID- 25853131
TI  - Blood disorders typically associated with renal transplantation.
AB  - Renal transplantation has become one of the most common surgical procedures
      performed to replace a diseased kidney with a healthy kidney from a donor. It can
      help patients with kidney failure live decades longer. However, renal
      transplantation also faces a risk of developing various blood disorders. The
      blood disorders typically associated with renal transplantation can be divided
      into two main categories: (1) Common disorders including post-transplant anemia
      (PTA), post-transplant lymphoproliferative disorder (PTLD), post-transplant
      erythrocytosis (PTE), and post-transplant cytopenias (PTC,
      leukopenia/neutropenia, thrombocytopenia, and pancytopenia); and (2) Uncommon but
      serious disorders including hemophagocytic syndrome (HPS), thrombotic
      microangiopathy (TMA), therapy-related myelodysplasia (t-MDS), and therapy
      related acute myeloid leukemia (t-AML). Although many etiological factors involve
      the development of post-transplant blood disorders, immunosuppressive agents, and
      viral infections could be the two major contributors to most blood disorders and
      cause hematological abnormalities and immunodeficiency by suppressing
      hematopoietic function of bone marrow. Hematological abnormalities and
      immunodeficiency will result in severe clinical outcomes in renal transplant
      recipients. Understanding how blood disorders develop will help cure these life
      threatening complications. A potential therapeutic strategy against post
      transplant blood disorders should focus on tapering immunosuppression or
      replacing myelotoxic immunosuppressive drugs with lower toxic alternatives,
      recognizing and treating promptly the etiological virus, bacteria, or protozoan,
      restoring both hematopoietic function of bone marrow and normal blood counts, and
      improving kidney graft survival. 

PMID- 25853132
TI  - Introduction to radiobiology of targeted radionuclide therapy.
AB  - During the last decades, new radionuclide-based targeted therapies have emerged
      as efficient tools for cancer treatment. Targeted radionuclide therapies (TRTs)
      are based on a multidisciplinary approach that involves the cooperation of
      specialists in several research fields. Among them, radiobiologists investigate
      the biological effects of ionizing radiation, specifically the molecular and
      cellular mechanisms involved in the radiation response. Most of the knowledge
      about radiation effects concerns external beam radiation therapy (EBRT) and
      radiobiology has then strongly contributed to the development of this therapeutic
      approach. Similarly, radiobiology and dosimetry are also assumed to be ways for
      improving TRT, in particular in the therapy of solid tumors, which are
      radioresistant. However, extrapolation of EBRT radiobiology to TRT is not
      straightforward. Indeed, the specific physical characteristics of TRT
      (heterogeneous and mixed irradiation, protracted exposure, and low absorbed dose
      rate) differ from those of conventional EBRT (homogeneous irradiation, short
      exposure, and high absorbed dose rate), and consequently the response of
      irradiated tissues might be different. Therefore, specific TRT radiobiology needs
      to be explored. Determining dose-effect correlation is also a prerequisite for
      rigorous preclinical radiobiology studies because dosimetry provides the
      necessary referential to all TRT situations. It is required too for developing
      patient-tailored TRT in the clinic in order to estimate the best dose for tumor
      control, while protecting the healthy tissues, thereby improving therapeutic
      efficacy. Finally, it will allow to determine the relative contribution of
      targeted effects (assumed to be dose-related) and non-targeted effects (assumed
      to be non-dose-related) of ionizing radiation. However, conversely to EBRT where
      it is routinely used, dosimetry is still challenging in TRT. Therefore, it
      constitutes with radiobiology, one of the main challenges of TRT in the future. 

PMID- 25853133
TI  - A case report of adrenocorticotropic hormone to treat recurrent focal segmental
      glomerular sclerosis post-transplantation and biomarker monitoring.
AB  - BACKGROUND: Recurrent focal segmental glomerular sclerosis (rFSGS) in renal
      transplant recipients (RTR) is difficult to predict and treat. Early rFSGS is
      likely from circulating factors and preformed antibodies. METHODS: We present the
      case of a 23-year-old white man who presented with rFSGS and acute renal failure,
      requiring dialysis 9-months after a 1-haplotype matched living-related
      transplant. We retrospectively analyzed serum samples from various clinical
      stages for rFSGS biomarkers: serum glomerular albumin permeability (Palb),
      soluble urokinase-type plasminogen activator receptor (suPAR) serum level with
      suPAR-beta3 integrin signaling on human podocytes, and angiotensin II type I
      receptor-antibody (AT1R-Ab) titer. RESULTS: All biomarkers were abnormal at 1
      year pre-transplant prior to initiation of dialysis and at the time of
      transplant. After initiation of hemodialysis, beta3 integrin activity on human
      podocytes, in response to patient serum, as well as AT1R-Ab were further
      elevated. At the time of biopsy-proven recurrence, all biomarkers were abnormally
      high. One week after therapy with aborted plasmapheresis (secondary to
      intolerance), and high dose steroids, the Palb and suPAR-beta3 integrin activity
      remained significantly positive. After 12-weeks of treatment with high-dose
      steroids, rituximab, and galactose, the patient remained hemodialysis-dependent.
      Three-months after his initial presentation, we commenced adrenocorticotropic
      hormone (ACTH, Acthar((r)) Gel), 80 units subcutaneously twice weekly. Four-weeks
      later, he was able to discontinue dialysis. After 8-months of maintenance ACTH
      therapy, his serum creatinine stabilized at 1.79 mg/dL with <1 g of proteinuria.
      CONCLUSION: ACTH therapy was associated with improvement in renal function within
      4 weeks. The use of rFSGS biomarkers may aid in predicting development of rFSGS.

PMID- 25853134
TI  - Neuroinflammation induced by intracerebroventricular injection of microbial
      neuraminidase.
AB  - In the present paper, we describe the facts that took place in the rat brain
      after a single injection of the enzyme neuraminidase from Clostridium perfringens
      into the right lateral ventricle. After injection, it diffused through the
      cerebrospinal fluid of the ipsilateral ventricle and the third ventricle, and
      about 400 MUm into the periventricular brain parenchyma. The expression of ICAM1
      in the endothelial cells of the periventricular vessels, IBA1 in microglia, and
      GFAP in astrocytes notably increased in the regions reached by the injected
      neuraminidase. The subependymal microglia and the ventricular macrophages begun
      to express IL1beta and some appeared to cross the ependymal layer. After about 4
      h of the injection, leukocytes migrated from large venules of the affected
      choroid plexus, the meninges and the local subependyma, and infiltrated the
      brain. The invading cells arrived orderly: first neutrophils, then macrophage
      monocytes, and last CD8alpha-positive T-lymphocytes and B-lymphocytes. Leukocytes
      in the ventricles and the perivascular zones penetrated the brain parenchyma
      passing through the ependyma and the glia limitans. Thus, it is likely that a
      great part of the damage produced by microorganism invading the brain may be due
      to their neuraminidase content. 

PMID- 25853135
TI  - The beneficial role of retinoids in glomerular disease.
AB  - The primary etiology of CKD is a direct consequence of initial dysfunction and
      injury of the glomerulus, the main filtration system. Podocytes are terminally
      differentiated epithelial cells in the glomerulus, whose major function is the
      maintenance of this renal filtration barrier. Podocyte injury is implicated in
      many glomerular diseases including focal segmental glomerular sclerosis and HIV
      associated nephropathy. In many of these diseased conditions, the podocyte can
      either undergo dedifferentiation and proliferation, apoptosis, or cell
      detachment. Regardless of the initial type of injury, the podocyte ultimately
      loses its functional capacity to maintain the glomerular filtration barrier.
      Significant injury resulting in a loss of the podocytes and failure to maintain
      the renal filtration barrier contributes to progressive kidney disease.
      Consequently, therapies that prevent podocyte injury and promote their
      regeneration will have a major clinical impact on glomerular disease. Retinoic
      acid (RA), which is a derivative of vitamin A, has many cellular functions
      including induction of cell differentiation, regulation of apoptosis, and
      inhibition of inflammation and proliferation. RA is required for kidney
      development and is essential for cellular differentiation in the setting of
      podocyte injury. The mechanism by which RA directs its beneficial effects is
      multifactorial, ranging from its anti-inflammatory and anti-fibrotic effects to a
      direct effect of upregulating podocyte differentiation markers in the podocyte.
      The focus of this review is to provide an overview of RA in kidney development
      and glomerular disease. We also highlight the key mechanism(s) by which RA
      restores podocyte differentiation markers and ameliorates glomerular disease. 

PMID- 25853136
TI  - The importance of evaluating primary midwifery care for improving the health of
      women and infants.
AB  - In most countries, maternal and newborn care is fragmented and focused on
      identification and treatment of pathology that affects only the minority of women
      and babies. Recently, a framework for quality maternal and newborn care was
      developed, which encourages a system-level shift to provide skilled care for all.
      This care includes preventive and supportive care that works to strengthen
      women's capabilities and focuses on promotion of normal reproductive processes
      while ensuring access to emergency treatment when needed. Midwifery care is
      pivotal in this framework, which contains several elements that resonate with the
      main dimensions of primary care. Primary health care is the first level of
      contact with the health system where most of the population's curative and
      preventive health needs can be fulfilled as close as possible to where people
      live and work. In this paper, we argue that midwifery as described in the
      framework requires the application of a primary care philosophy for all
      childbearing women and infants. Evaluation of the implementation of the framework
      should therefore include tools to monitor the performance of primary midwifery
      care. 

PMID- 25853137
TI  - A review of the nonpressor and nonantidiuretic actions of the hormone
      vasopressin.
AB  - The pressor and antidiuretic actions of arginine vasopressin (AVP) have been well
      documented. This review focuses on the less widely appreciated actions of AVP
      which also have important physiologic functions and when better understood may
      provide important insights into common disease states. These actions include
      effects on pain perception and bone structure as well as important relationships
      to the varied components of metabolic syndrome. These include effects on blood
      glucose, lipid levels, and blood pressure. AVP may also play a role in the
      progression of chronic kidney disease and effect physiologic changes relating to
      aging, abnormal social behavior, and cognitive function. Important cellular
      responses including cell proliferation, inflammation, and control of infection
      and their relationship to AVP are described. Finally, the effects of AVP on
      hemostasis and the hypothalamic-pituitary-adrenal axis are noted. The goal of
      this summary of the various actions of AVP is to direct attention to the
      potential benefits of research in these underemphasized areas of importance. 

PMID- 25853138
TI  - Molecular cloning and characterization of novel phytocystatin gene from turmeric,
      Curcuma longa.
AB  - Phytocystatin, a type of protease inhibitor (PI), plays major roles in plant
      defense mechanisms and has been reported to show antipathogenic properties and
      plant stress tolerance. Recombinant plant PIs are gaining popularity as potential
      candidates in engineering of crop protection and in synthesizing medicine. It is
      therefore crucial to identify PI from novel sources like Curcuma longa as it is
      more effective in combating against pathogens due to its novelty. In this study,
      a novel cDNA fragment encoding phytocystatin was isolated using degenerate PCR
      primers, designed from consensus regions of phytocystatin from other plant
      species. A full-length cDNA of the phytocystatin gene, designated CypCl, was
      acquired using 5'/3' rapid amplification of cDNA ends method and it has been
      deposited in NCBI database (accession number KF545954.1). It has a 687 bp long
      open reading frame (ORF) which encodes 228 amino acids. BLAST result indicated
      that CypCl is similar to cystatin protease inhibitor from Cucumis sativus with
      74% max identity. Sequence analysis showed that CypCl contains most of the motifs
      found in a cystatin, including a G residue, LARFAV-, QxVxG sequence, PW
      dipeptide, and SNSL sequence at C-terminal extension. Phylogenetic studies also
      showed that CypCl is related to phytocystatin from Elaeis guineensis. 

PMID- 25853139
TI  - Neuronal nitric oxide synthase is dislocated in type I fibers of myalgic muscle
      but can recover with physical exercise training.
AB  - Trapezius myalgia is the most common type of chronic neck pain. While physical
      exercise reduces pain and improves muscle function, the underlying mechanisms
      remain unclear. Nitric oxide (NO) signaling is important in modulating cellular
      function, and a dysfunctional neuronal NO synthase (nNOS) may contribute to an
      ineffective muscle function. This study investigated nNOS expression and
      localization in chronically painful muscle. Forty-one women clinically diagnosed
      with trapezius myalgia (MYA) and 18 healthy controls (CON) were included in the
      case-control study. Subsequently, MYA were randomly assigned to either 10 weeks
      of specific strength training (SST, n = 18), general fitness training (GFT, n =
      15), or health information (REF, n = 8). Distribution of fiber type, cross
      sectional area, and sarcolemmal nNOS expression did not differ between MYA and
      CON. However, MYA showed increased sarcoplasmic nNOS localization (18.8 +/- 12
      versus 12.8 +/- 8%, P = 0.049) compared with CON. SST resulted in a decrease of
      sarcoplasm-localized nNOS following training (before 18.1 +/- 12 versus after
      12.0 +/- 12%; P = 0,027). We demonstrate that myalgic muscle displays altered
      nNOS localization and that 10 weeks of strength training normalize these
      disruptions, which supports previous findings of impaired muscle oxygenation
      during work tasks and reduced pain following exercise. 

PMID- 25853140
TI  - Imbalance of the nerve growth factor and its precursor as a potential biomarker
      for diabetic retinopathy.
AB  - Our previous studies have demonstrated that diabetes-induced oxidative stress
      alters homeostasis of retinal nerve growth factor (NGF) resulting in accumulation
      of its precursor, proNGF, at the expense of NGF which plays a critical role in
      preserving neuronal and retinal function. This imbalance coincided with retinal
      damage in experimental diabetes. Here we test the hypothesis that alteration of
      proNGF and NGF levels observed in retina and vitreous will be mirrored in serum
      of diabetic patients. Blood and vitreous samples were collected from patients
      (diabetic and nondiabetic) undergoing vitrectomy at Georgia Regents University
      under approved IRB. Levels of proNGF, NGF, and p75(NTR) shedding were detected
      using Western blot analysis. MMP-7 activity was also assayed. Diabetes-induced
      proNGF expression and impaired NGF expression were observed in vitreous and
      serum. Vitreous and sera from diabetic patients (n = 11) showed significant 40.8
      fold and 3.6-fold increases, respectively, compared to nondiabetics (n = 9). In
      contrast, vitreous and sera from diabetic patients showed significant 44% and 64%
      reductions in NGF levels, respectively, compared to nondiabetics. ProNGF to NGF
      ratios showed significant correlation between vitreous and serum. Further
      characterization of diabetes-induced imbalance in the proNGF to NGF ratio will
      facilitate its utility as an early biomarker for diabetic complications. 

PMID- 25853143
TI  - Retracted: Variations in stable carbon isotope composition and leaf traits of
      Picea schrenkiana var. tianschanica along an altitude gradient in Tianshan
      Mountains, Northwest China.
AB  - [This retracts the article DOI: 10.1155/2014/243159.]. 

PMID- 25853142
TI  - Cost-effectiveness of anticoagulation in patients with nonvalvular atrial
      fibrillation with edoxaban compared to warfarin in Germany.
AB  - We compared the cost-utility analysis for edoxaban at both doses with that of
      dabigatran at both doses, rivaroxaban, and apixaban (non vitamin K antagonist
      oral anticoagulants, NOAC) in a German population. Data of clinical outcome
      events were taken from edoxaban's ENGAGE-AF, dabigatran's RE-LY, rivaroxaban's
      ROCKET, and apixaban's ARISTOTLE trials. The base-case analyses of a 65-year-old
      person with a CHADS2 score >1 gained 0.17 and 0.21 quality-adjusted life years
      over warfarin for 30 mg od and 60 mg od edoxaban, respectively. The incremental
      cost-effectiveness ratio was 50.000 and 68.000 euro per quality-adjusted life
      years for the higher and lower dose of edoxaban (Monte Carlo simulation). These
      findings were also similar to those for apixaban and more cost-effective than the
      other NOAC regimens. The current market costs for direct oral anticoagulants are
      high in relation to the quality of life gained from a German public health care
      insurance perspective. The willingness-to-pay threshold was lowest for 60 mg
      edoxaban compared to all direct oral anticoagulants and for 30 mg edoxaban
      compared to dabigatran and rivaroxaban. 

PMID- 25853144
TI  - Physiological responses of Kosteletzkya virginica to coastal wetland soil.
AB  - Effects of salinity on growth and physiological indices of Kosteletzkya virginica
      seedlings were studied. Plant height, fresh weight (FW), dry weight (DW), and net
      photosynthetic rate (Pn) increased at 100 mM NaCl and slightly declined at 200
      mM, but higher salinity induced a significant reduction. Chlorophyll content,
      stomatal conductance (Gs), intercellular CO2 concentration (Ci), and
      transpiration rate (E) were not affected under moderate salinities, while
      markedly decreased at severe salinities except for the increased Ci at 400 mM
      NaCl. Furthermore, no significant differences of Fv/Fm and PhiPSII were found at
      lower than 200 mM NaCl, whereas higher salinity caused the declines of Fv/Fm,
      PhiPSII, and qP similar to Pn, accompanied with higher NPQ. Besides, salt stress
      reduced the leaf RWC, but caused the accumulation of proline to alleviate osmotic
      pressure. The increased activities of antioxidant enzymes maintained the normal
      levels of MDA and relative membrane permeability. To sum up, Kosteletzkya
      virginica seedlings have good salt tolerance and this may be partly attributed to
      its osmotic regulation and antioxidant capacity which help to maintain water
      balance and normal ROS level to ensure the efficient photosynthesis. These
      results provided important implications for Kosteletzkya virginica acting as a
      promising multiuse species for reclaiming coastal soil.

PMID- 25853141
TI  - Modulation of microRNAs by phytochemicals in cancer: underlying mechanisms and
      translational significance.
AB  - MicroRNAs (miRNAs) are small, endogenous noncoding RNAs that regulate a variety
      of biological processes such as differentiation, development, and survival.
      Recent studies suggest that miRNAs are dysregulated in cancer and play critical
      roles in cancer initiation, progression, and chemoresistance. Therefore,
      exploitation of miRNAs as targets for cancer prevention and therapy could be a
      promising approach. Extensive evidence suggests that many naturally occurring
      phytochemicals regulate the expression of numerous miRNAs involved in the
      pathobiology of cancer. Therefore, an understanding of the regulation of miRNAs
      by phytochemicals in cancer, their underlying molecular mechanisms, and
      functional consequences on tumor pathophysiology may be useful in formulating
      novel strategies to combat this devastating disease. These aspects are discussed
      in this review paper with an objective of highlighting the significance of these
      observations from the translational standpoint. 

PMID- 25853145
TI  - Formulation and evaluation of galantamine gel as drug reservoir in transdermal
      patch delivery system.
AB  - Galantamine hydrobromide is formulated in tablets and capsules prescribed through
      oral delivery for the treatment of Alzheimer's disease. However, oral delivery of
      drugs can cause severe side effects such as nausea, vomiting, and
      gastrointestinal disturbance. Transdermal delivery of galantamine hydrobromide
      could avoid these unwanted side effects. In this work, galantamine hydrobromide
      was formulated in gel drug reservoir which was then fabricated in the transdermal
      patch. The in vitro drug release studies revealed that the drug release from the
      donor chamber to receptor chamber of Franz diffusion cell was affected by the
      amount of polymer, amount of neutralizer, amount of drug, types of permeation
      enhancer, and amount of permeation enhancer. Visual observations of the gels
      showed that all formulated gels are translucent, homogeneous, smooth, and stable.
      These gels have pH in the suitable range for skin. The gel also showed high drug
      content uniformity. Hence, this formulation can be further used in the
      preparation of transdermal patch drug delivery system. 

PMID- 25853147
TI  - Covalent incorporation of the surfactant into high internal phase emulsion
      templated polymeric foams.
AB  - High internal phase emulsions of water in cyclooctene stabilised by sorbitan
      monooleate (Span 80) were cured by ring-opening metathesis polymerisation to
      release fully open macroporous polymer foams wherein the surfactant was
      covalently incorporated into the poly(cyclooctene) strands via chain transfer
      reactions. 

PMID- 25853148
TI  - Porous ZrO2 sheets synthesized using an ionothermal method and their absorption
      properties.
AB  - In this study, porous ZrO2 sheets were synthesized using an ionothermal method
      combined with heat treatments at 400, 600 and 800  degrees C. Following
      ionothermal synthesis, NH4Zr2F9 with a sheet-like structure was obtained. After
      heat treatment, the NH4Zr2F9 was transformed into monoclinic ZrO2 with a porous
      sheet structure. The ZrO2 was characterized using XRD, FT-IR, FE-SEM TEM, TG-DTA,
      BET, and zeta potential analysis. The specific surface area of the samples
      increased with heat treatment temperature, being 12, 17, and 19 m(2) g(-1) for
      400, 600, and 800  degrees C, respectively. In addition, measurement of the zeta
      potential of the samples in KCl solution showed that all samples were negatively
      charged at pH 7, and had different isoelectric points. Adsorption was evaluated
      using methylene blue and methyl orange and the results indicated that samples
      heated at different temperatures possessed different selectivities for cationic
      and anionic dyes. 

PMID- 25853146
TI  - Fibrin gel as an injectable biodegradable scaffold and cell carrier for tissue
      engineering.
AB  - Due to the increasing needs for organ transplantation and a universal shortage of
      donated tissues, tissue engineering emerges as a useful approach to engineer
      functional tissues. Although different synthetic materials have been used to
      fabricate tissue engineering scaffolds, they have many limitations such as the
      biocompatibility concerns, the inability to support cell attachment, and
      undesirable degradation rate. Fibrin gel, a biopolymeric material, provides
      numerous advantages over synthetic materials in functioning as a tissue
      engineering scaffold and a cell carrier. Fibrin gel exhibits excellent
      biocompatibility, promotes cell attachment, and can degrade in a controllable
      manner. Additionally, fibrin gel mimics the natural blood-clotting process and
      self-assembles into a polymer network. The ability for fibrin to cure in situ has
      been exploited to develop injectable scaffolds for the repair of damaged cardiac
      and cartilage tissues. Additionally, fibrin gel has been utilized as a cell
      carrier to protect cells from the forces during the application and cell delivery
      processes while enhancing the cell viability and tissue regeneration. Here, we
      review the recent advancement in developing fibrin-based biomaterials for the
      development of injectable tissue engineering scaffold and cell carriers. 

PMID- 25853149
TI  - Metastatic prostate cancer mimicking thrombotic thrombocytopenic purpura.

PMID- 25853151
TI  - World: Industry confronted with child labour issue.

PMID- 25853150
TI  - Early or late antibiotic intervention prevents Helicobacter pylori-induced
      gastric cancer in a mouse model.
AB  - H. pylori infection causes gastritis, peptic ulcers and gastric cancer.
      Eradicating H. pylori prevents ulcers, but to what extent this prevents cancer
      remains unknown, especially if given after intestinal metaplasia has developed.
      H. pylori infected wild-type (WT) mice do not develop cancer, but mice lacking
      the tumor suppressor p27 do so, thus providing an experimental model of H. pylori
      induced cancer. We infected p27-deficient mice with H. pylori strain SS1 at 6-8
      weeks of age. Persistently H. pylori-infected WT C57BL/6 mice served as controls.
      Mice in the eradication arms received antimicrobial therapy (omeprazole,
      metronidazole and clarithromycin) either "early" (at 15 weeks post infection,
      WPI) or "late" at 45 WPI. At 70 WPI, mice were euthanized for H. pylori
      determination, histopathology and cytokine/chemokine expression. Persistently
      infected mice developed premalignant lesions including high-grade dysplasia,
      whereas those given antibiotics did not. Histologic activity scores in the
      eradication groups were similar to each other, and were significantly decreased
      compared with controls for inflammation, epithelial defects, hyperplasia,
      metaplasia, atrophy and dysplasia. IP-10 and MIG levels in groups that received
      antibiotics were significantly lower than controls. There were no significant
      differences in expression of IFN-gamma, TNF-alpha, IL-1beta, RANTES, MCP-1, MIP
      1alpha or MIP-1beta among the three groups. Thus, H. pylori eradication given
      either early or late after infection significantly attenuated gastric
      inflammation, gastric atrophy, hyperplasia, and dysplasia in the p27-deficient
      mice model of H. pylori-induced gastric cancer, irrespective of the timing of
      antibiotic administration. This was associated with reduced expression of IP-10
      and MIG.

PMID- 25853152
TI  - USA: Red Cross tobacco funding risks global brand.

PMID- 25853153
TI  - Indonesia: Warnings need stronger enforcement.

PMID- 25853155
TI  - Enantioselective radical addition to ketimines: a synthetic route towards
      alpha,alpha-disubstituted alpha-amino acids.

PMID- 25853154
TI  - Membrane trafficking. Preface.

PMID- 25853156
TI  - Comments.

PMID- 25853157
TI  - Erratum regarding "Pulmonary Hypertension in CKD" (Am J Kidney Dis.
      2013;61[4]:612-622).
AB  - In the Narrative Review entitled "Pulmonary Hypertension in CKD" that appeared in
      the April 2013 issue ofAJKD (Bolignano et al, volume 61, issue 4, pages 612-622),
      Fig 1 contained labeling errors, panel B appeared in duplicate, and panel A was
      missing.

PMID- 25853158
TI  - [Bulletin editorial for Issue 2].

PMID- 25853159
TI  - [ Appointments at service centers -- conflicts of interest and predetermined
      breaking points].

PMID- 25853160
TI  - [Looking into the SHI VSG: pending bills].

PMID- 25853161
TI  - [Love in the workplace -- depart or stay?].

PMID- 25853162
TI  - Increasing pressure on nurses a major challenge--Trim.

PMID- 25853163
TI  - The making of the MECA.

PMID- 25853164
TI  - [Canadian advertising on food and beverages to children. New nutrient criteria].

PMID- 25853165
TI  - [Osteoarthritis. Eat better, suffer less].

PMID- 25853166
TI  - [Liquid sugar].

PMID- 25853167
TI  - [Rotavirus].

PMID- 25853168
TI  - [A passionate relief].

PMID- 25853169
TI  - [From 1932 to 1972. Colony Nurses. Two authors relate how these women have marked
      the history of nursing in Quebec].

PMID- 25853170
TI  - [Crimes justified by honor. Act to support potential victims].

PMID- 25853171
TI  - [Drugs for children. We need more studies].

PMID- 25853172
TI  - The impact of note taking style and note availability at retrieval on mock
      jurors' recall and recognition of trial information.
AB  - Jurors forget critical trial information and what they do recall can be
      inaccurate. Jurors' recall of trial information can be enhanced by permitting
      them to take notes during a trial onto blank sheets of paper (henceforth called
      freestyle note taking). A recent innovation is the trial-ordered-notebook (TON)
      for jurors, which is a notebook containing headings outlining the trial
      proceedings and which has space beneath each heading for notes. In a direct
      comparison, TON note takers recalled more trial information than freestyle note
      takers. This study investigated whether or not note taking improves recall as a
      result of enhanced encoding or as a result of note access at retrieval. To assess
      this, mock jurors watched and freely recalled a trial video with one-fifth taking
      no notes, two-fifths taking freestyle notes and two-fifths using TONs. During
      retrieval, half of the freestyle and TON note takers could access their notes.
      Note taking enhanced recall, with the freestyle note takers and TON note takers
      without note access performing equally as well. Note taking therefore enhances
      encoding. Recall was greatest for the TON note takers with note access,
      suggesting a retrieval enhancement unique to this condition. The theoretical and
      applied implications of these findings are discussed. 

PMID- 25853173
TI  - Early neurone loss in Alzheimer's disease: cortical or subcortical?
AB  - Alzheimer's disease (AD) is a degenerative disorder where the distribution of
      pathology throughout the brain is not random but follows a predictive pattern
      used for pathological staging. While the involvement of defined functional
      systems is fairly well established for more advanced stages, the initial sites of
      degeneration are still ill defined. The prevailing concept suggests an origin
      within the transentorhinal and entorhinal cortex (EC) from where pathology
      spreads to other areas. Still, this concept has been challenged recently
      suggesting a potential origin of degeneration in nonthalamic subcortical nuclei
      giving rise to cortical innervation such as locus coeruleus (LC) and nucleus
      basalis of Meynert (NbM). To contribute to the identification of the early site
      of degeneration, here, we address the question whether cortical or subcortical
      degeneration occurs more early and develops more quickly during progression of
      AD. To this end, we stereologically assessed neurone counts in the NbM, LC and EC
      layer-II in the same AD patients ranging from preclinical stages to severe
      dementia. In all three areas, neurone loss becomes detectable already at
      preclinical stages and is clearly manifest at prodromal AD/MCI. At more advanced
      AD, cell loss is most pronounced in the NbM > LC > layer-II EC. During early AD,
      however, the extent of cell loss is fairly balanced between all three areas
      without clear indications for a preference of one area. We can thus not rule out
      that there is more than one way of spreading from its site of origin or that
      degeneration even occurs independently at several sites in parallel.

PMID- 25853175
TI  - The effects of amphotericin B on angiogenesis in chick chorioallantoic membrane.
AB  - OBJECTIVE: Amphotericin B (AmB) is widely used as a mainstay in the treatment of
      sight-threatening fungal endophthalmitis. From the time that itraconazole was
      discovered to have a previously unknown anti-angiogenic activity, we have
      suspected that AmB may have possible effects on ocular angiogenesis. The purpose
      of this study was to evaluate the in vivo anti-angiogenic effect of AmB in the
      chick chorioallantoic membrane (CAM) model. MATERIALS AND METHODS: Atak-S type
      fertilized eggs obtained from the Poultry Institution were used. The eggs were
      kept under 37  degrees C at 85-90% relative humidity throughout the experiment.
      Amphotericin B was prepared in two different concentrations (AmB 125 MUg/1 mL and
      0.125 MUg/1 mL). The CAMs treated with sterile distilled water was specified as
      controls. About 0.1 mL of each containing 12.5 and 0.0125 ug of AmB,
      respectively, were dropped to CAM surface. Thirteen eggs were used for each
      group. The results were evaluated at the 48th hour of the administration of the
      drugs and recorded by digital camera. RESULTS: A reduction of angiogenesis in CAM
      area which treated with 125 MUg/1 mL of AmB was appreciable macroscopically. The
      affected areas showed impaired radial arrangement of small vessels with the
      presence of avascular zone at periphery. The dose of 0.125 MUg/1 mL AmB did not
      show any visible anti-angiogenic effect. Numerous blood vessels with a radially
      arranged pattern developed toward the periphery after 48 h of treatment. In the
      CAMs that treated with distilled water, physiological angiogenesis was observed
      in allantoic vessels. Vessel formation seems to be similar in CAMs treated with
      0.125 MUg/1 mL AmB with the presence of visibly non-malformed alive embryos.
      CONCLUSIONS: The present study gives the impression that AmB has the capacity to
      serve as an anti-angiogenic treatment. As it is a preliminary CAM study only,
      further studies on both animals and humans are required.

PMID- 25853174
TI  - Amyloid accelerates tau propagation and toxicity in a model of early Alzheimer's
      disease.
AB  - INTRODUCTION: In early stages of Alzheimer's disease (AD), neurofibrillary
      tangles (NFT) are largely restricted to the entorhinal cortex and medial temporal
      lobe. At later stages, when clinical symptoms generally occur, NFT involve
      widespread limbic and association cortices. At this point in the disease, amyloid
      plaques are also abundantly distributed in the cortex. This observation from
      human neuropathological studies led us to pose two alternative hypotheses: that
      amyloid in the cortex is permissive for the spread of tangles from the medial
      temporal lobe, or that these are co-occurring but not causally related events
      simply reflecting progression of AD pathology. RESULTS: We now directly test the
      hypothesis that cortical amyloid acts as an accelerant for spreading of tangles
      beyond the medial temporal lobe. We crossed rTgTauEC transgenic mice that
      demonstrate spread of tau from entorhinal cortex to other brain structures at
      advanced age with APP/PS1 mice, and examined mice with either NFTs, amyloid
      pathology, or both. We show that concurrent amyloid deposition in the cortex 1)
      leads to a dramatic increase in the speed of tau propagation and an extraordinary
      increase in the spread of tau to distal brain regions, and 2) significantly
      increases tau-induced neuronal loss. CONCLUSIONS: These data strongly support the
      hypothesis that cortical amyloid accelerates the spread of tangles throughout the
      cortex and amplifies tangle-associated neural system failure in AD.

PMID- 25853176
TI  - Effects of isotretinoin on the inflammatory markers and the platelet counts in
      patients with acne vulgaris.
AB  - OBJECTIVE: Oral isotretinoin is an efficient treatment used commonly in treating
      the moderate and severe acne. It has various side effects that affect many
      systems in the body. In this study, we are planning to examine the possible
      effects of the oral isotretinoin on platelet density, mean platelet volume,
      neutrophil lymphocyte rate, platelet lymphocyte rate, and red-blood-cell
      distribution width level. METHODS: Twenty-eight males and 84 females, 112
      patients in total, diagnosed with acne vulgaris and receiving oral isotretinoin
      treatment were examined retrospectively. The full blood parameters of the
      patients before the treatment and in the third month of the treatment were
      recorded. RESULTS: A statistically meaningful increase was observed in the
      platelet density, hemoglobin levels. And a statistically significant decrease has
      been determined in the red-blood-cell distribution width level while no
      meaningful differences were detected in the mean platelet volume, neutrophil
      lymphocyte rate, platelet lymphocyte rate, and white blood cell count.
      CONCLUSIONS: The oral isotretinoin treatment has been demonstrated as having
      increased the platelet density, hemoglobin levels and having decreased red-blood
      cell distribution width level significantly.

PMID- 25853177
TI  - The ocular surface side effects of an anti-psychotic drug, clozapine.
AB  - PURPOSE: The purpose of this study is to investigate the effects of long-term
      clozapine usage on tear film stability and corneal topographic parameters.
      MATERIAL AND METHODS: The study was conducted between March 2014 and November
      2014. Thirty patients who were diagnosed of schizophrenia and have been under
      clozapine treatment for 2.73 +/- 0.73 years (range 2-4 years) were involved in
      this study (group 1). Thirty healthy subjects (group 2) who have statistically
      similar demographic features compared with the group 1, were involved as a
      control group. Full ophthalmologic examination with biomicroscopy and indirect
      ophthalmoscopy was applied. Corneal topographic parameters were measured using
      the Pentacam HR and Schirmer test was done. Statistical analysis of the subjects
      was evaluated by using SPSS (for Windows version 16.0; SPSS Inc., Chicago, IL)
      program. RESULTS: K1 value was measured as 43.39 +/- 0.17 D (43-43.50 D) and K2
      value was measured as 43.39 +/- 0.06 D (43.30-43.50 D) in groups 1 and 2,
      respectively. In groups 1 and 2, K2 values were noted as 43.86 +/- 0.27 D (43.50
      44.50 D) and 43.72 +/- 0.18 D (43.50-44.00 D), respectively. Central corneal
      thickness was found to be 523.93 +/- 15.66 um (495-554 um) and 550.13 +/- 1.03 um
      (520-580 um) in groups 1 and 2, respectively. Corneal apex thickness was 525.86
      +/- 15.75 um (497-556 um) in group 1 and 551.60 +/- 14.99 um (521-581 um) in
      group 2. The corneal thickness of thinnest location was 520.93 +/- 15.60 um (492
      551 um) and 548.06 +/- 15.17 um (518-578 um) in groups 1 and 2, respectively.
      Corneal volume was determined as 58.13 +/- 3.46 mm(3) (52-64 mm(3)) in group 1
      and 60.73 +/- 3.76 mm(3) (54-66 mm(3)) in group 2. The Schirmer test showed
      thickness of 3.33 +/- 0.72 mm (2-4 mm) and 13.60 +/- 1.59 mm (11-16 mm) in groups
      1 and 2, respectively. The mean fluorescein break-up time was 5.40 +/- 1.50 s (3
      8 s) and 12.46 +/- 1.40 s (10-14 s) in groups 1 and 2, respectively. There was a
      statistically significant difference in the Schirmer test, fluorescein break-up
      time, central corneal thickness, corneal apex, and the thinnest corneal location
      thickness between the two groups. CONCLUSION: Clozapine may induce dry eye
      syndrome and thus may lead to morphological alterations in corneal parameters
      through its anticholinergic and antidopaminergic activities. Because of these
      corneal alterations, one should be aware of evaluating patients having diseases
      like glaucoma or preoperative selection of corneal refractive surgery candidates.

PMID- 25853179
TI  - Vapor Phase Processing of alpha-Fe2O3 Photoelectrodes for Water Splitting: An
      Insight into the Structure/Property Interplay.
AB  - Harvesting radiant energy to trigger water photoelectrolysis and produce clean
      hydrogen is receiving increasing attention in the search of alternative energy
      resources. In this regard, hematite (alpha-Fe2O3) nanostructures with controlled
      nano-organization have been fabricated and investigated for use as anodes in
      photoelectrochemical (PEC) cells. The target systems have been grown on
      conductive substrates by plasma enhanced-chemical vapor deposition (PE-CVD) and
      subjected to eventual ex situ annealing in air to further tailor their structure
      and properties. A detailed multitechnique approach has enabled to elucidate the
      interrelations between system characteristics and the generated photocurrent. The
      present alpha-Fe2O3 systems are characterized by a high purity and hierarchical
      morphologies consisting of nanopyramids/organized dendrites, offering a high
      contact area with the electrolyte. PEC data reveal a dramatic response
      enhancement upon thermal treatment, related to a more efficient electron
      transfer. The reasons underlying such a phenomenon are elucidated and discussed
      by transient absorption spectroscopy (TAS) studies of photogenerated charge
      carrier kinetics, investigated on different time scales for the first time on PE
      CVD Fe2O3 nanostructures. 

PMID- 25853181
TI  - 25(th) anniversary state-of-the-art expert discussion with Steven S. Rothenberg,
      MD, on the evolution of thoracic surgery.

PMID- 25853180
TI  - Wheat rusts never sleep but neither do sequencers: will pathogenomics transform
      the way plant diseases are managed?
AB  - Field pathogenomics adds highly informative data to surveillance surveys by
      enabling rapid evaluation of pathogen variability, population structure and host
      genotype. 

PMID- 25853178
TI  - Potent effects of dioscin against liver fibrosis.
AB  - We previously reported the promising effects of dioscin against liver injury, but
      its effect on liver fibrosis remains unknown. The present work investigated the
      activities of dioscin against liver fibrosis and the underlying molecular
      mechanisms. Dioscin effectively inhibited the cell viabilities of HSC-T6, LX-2
      and primary rat hepatic stellate cells (HSCs), but not hepatocytes. Furthermore,
      dioscin markedly increased peroxisome proliferator activated receptor-gamma (PPAR
      gamma) expression and significantly reduced a-smooth muscle actin (alpha-SMA),
      transforming growth factor-beta1 (TGF-beta1), collagen alpha1 (I) (COL1A1) and
      collagen alpha1 (III) (COL3A1) levels in vitro. Notably, dioscin inhibited HSCs
      activation and induced apoptosis in activated HSCs. In vivo, dioscin
      significantly improved body weight and hydroxylproline, laminin, alpha-SMA, TGF
      beta1, COL1A1 and COL3A1 levels, which were confirmed by histopathological
      assays. Dioscin facilitated matrix degradation, and exhibited hepatoprotective
      effects through the attenuation of oxidative stress and inflammation, in addition
      to exerting anti-fibrotic effects through the modulation of the TGF-beta1/Smad,
      Wnt/beta-catenin, mitogen-activated protein kinase (MAPK) and mitochondrial
      signaling pathways, which triggered the senescence of activated HSCs. In
      conclusion, dioscin exhibited potent effects against liver fibrosis through the
      modulation of multiple targets and signaling pathways and should be developed as
      a novel candidate for the treatment of liver fibrosis in the future. 

PMID- 25853182
TI  - Robotic-assisted laparoscopic surgery of urachal anomalies: a single-center
      experience.
AB  - OBJECTIVES: Urachal anomalies typically arise from abnormalities in the process
      of urachal closure. Urachal pathology causes morbidity (pain, umbilical drainage)
      and may harbor malignancy. Robotic-assisted laparoscopic surgery may be an
      attractive alternative to the open approach, which has only been studied in rare
      case reports. Herein, we report our experience with robotic surgery for benign
      urachal anomalies. MATERIALS AND METHODS: From 2007 to 2013, we identified 11
      patients (8 adult, 3 pediatric) who underwent robotic-assisted laparoscopic
      surgery for urachal pathology. Surgery was performed with a transperitoneal
      approach with careful dissection starting lateral to the median umbilical
      vessels, ensuring removal of all urachal tissue from the umbilicus to the
      bladder. When necessary, cystoscopic evaluation was performed to assist with the
      intravesical dissection. Patient demographics, postoperative narcotic use
      (morphine milligram equivalents), pathologic data, and operative time were
      evaluated. RESULTS: There were 4 female and 7 male patients with a median age of
      51 years (range, 12-72 years). Median operative time was 85 minutes (range, 51
      224 minutes), and median blood loss was 20 mL (range, 5-400 mL). Only 6 patients
      required narcotics for pain control postoperatively, with a median of 7.5 mg of
      peroral morphine used. Median length of hospital stay was 1 day (range, 1-2
      days), and median duration of catheterization was 5.5 days (range, 1-10 days).
      One patient underwent concurrent robotic prostatectomy. Pathology was benign in
      all cases. Median follow-up was 15.5 months (range, 1-18 months). Surgery was
      well tolerated as only 1 patient had a complication (Clavien class 1; a urinary
      tract infection treated with oral antibiotics). CONCLUSIONS: Urachal pathology is
      well suited to robotic-assisted laparoscopic surgery. The urachus is immediately
      visualized upon entry into the abdomen. The procedure can be performed safely,
      with short hospitalization and minimal narcotic pain control required.

PMID- 25853183
TI  - A novel spherical magnetic compression device for colorectal anastomosis in a
      Swine model.
AB  - BACKGROUND: We designed a novel, spherical magnetic compression colorectal
      anastomosis device and established a swine model to assess the feasibility and
      safety, as well as advantages, of the device. METHODS AND MATERIALS: Fifteen
      animals were divided into five groups (sacrificed on Days 3, 5 7, 9, and 14) with
      3 in each group. In each group, a magnetic compression device was used in 2
      animals (experimental animals), and a stapled device was used in 1 animal
      (control animal). Feeding status, bowel movements, the discharge time of the
      magnetic anastomosis device, burst pressure, and magnetic field strength were
      recorded. Gross anatomical and histological examinations were performed. RESULTS:
      The average device discharge time was 7.5 days. The burst pressure increased over
      time for both the experimental and control animals. Both the gross anatomical and
      histological examinations suggested that the inflammatory reaction was milder.
      Healing occurred more quickly, and the incidence of complications was lower for
      the experimental animals than for the control animals. CONCLUSIONS: The potential
      benefits of the spherical magnetic compression colorectal anastomosis device,
      relative to the stapled device, were in terms of effectiveness and complication
      incidence, which encourages us to further study its application in
      gastrointestinal anastomosis.

PMID- 25853184
TI  - Sex, violence and HIV on the inside: cultures of violence, denial, gender
      inequality and homophobia negatively influence the health outcomes of those in
      closed settings.
AB  - To map the context of HIV in closed settings in Papua New Guinea (PNG), semi
      structured interviews were undertaken with 56 prisoners and detainees and 60 key
      stakeholders. The nature of HIV-related risk differs for detained women and men,
      and reflects important gender-based issues present in PNG society more broadly.
      Women in detention are vulnerable to sexual violence and exploitation and at
      greatest risk of HIV while detained in police holding cells, where they are
      typically supervised by male officers, in contrast to prisons, where they have
      little contact with male staff. HIV risk for men in prison is associated with
      consensual and non-consensual sex; this risk is perpetuated by a pervasive
      culture of denial and institutionalised homophobia. The illegal nature of sodomy
      and male-to-male sex provides Correctional Services the legal grounds by which to
      refuse access to condoms for prisoners. Addressing HIV risk among detained men
      and women in PNG requires the reform of legislation, police and prison practices
      and an understanding of broader structural problems of gender-based violence and
      stigma and discrimination. 

PMID- 25853187
TI  - Image of the month: Caroli syndrome: central dot sign on CT.

PMID- 25853189
TI  - Image of the month: Intraperitoneal abscess drainage using
      esophagogastroduodenoscopy.

PMID- 25853188
TI  - Image of the month: Hepatic visceral larva migrans.

PMID- 25853190
TI  - Image of the month: Heterotopic gastric mucosa of the rectum presenting as rectal
      bleeding.

PMID- 25853185
TI  - Combinatorial activities of SHORT VEGETATIVE PHASE and FLOWERING LOCUS C define
      distinct modes of flowering regulation in Arabidopsis.
AB  - BACKGROUND: The initiation of flowering is an important developmental transition
      as it marks the beginning of the reproductive phase in plants. The MADS-box
      transcription factors (TFs) FLOWERING LOCUS C (FLC) and SHORT VEGETATIVE PHASE
      (SVP) form a complex to repress the expression of genes that initiate flowering
      in Arabidopsis. Both TFs play a central role in the regulatory network by
      conferring seasonal patterns of flowering. However, their interdependence and
      biological relevance when acting as a complex have not been extensively studied.
      RESULTS: We characterized the effects of both TFs individually and as a complex
      on flowering initiation using transcriptome profiling and DNA-binding occupancy.
      We find four major clusters regulating transcriptional responses, and that DNA
      binding scenarios are highly affected by the presence of the cognate partner.
      Remarkably, we identify genes whose regulation depends exclusively on
      simultaneous action of both proteins, thus distinguishing between the specificity
      of the SVP:FLC complex and that of each TF acting individually. The downstream
      targets of the SVP:FLC complex include a higher proportion of genes regulating
      floral induction, whereas those bound by either TF independently are biased
      towards floral development. Many genes involved in gibberellin-related processes
      are bound by the SVP:FLC complex, suggesting that direct regulation of
      gibberellin metabolism by FLC and SVP contributes to their effects on flowering.
      CONCLUSIONS: The regulatory codes controlled by SVP and FLC were deciphered at
      the genome-wide level revealing substantial flexibility based on dependent and
      independent DNA binding that may contribute to variation and robustness in the
      regulation of flowering.

PMID- 25853191
TI  - Video of the month. Modified peroral endoscopic myotomy.

PMID- 25853196
TI  - Combination therapy with sorafenib and radiofrequency ablation for BCLC stage 0
      B1 hepatocellular carcinoma.

PMID- 25853197
TI  - Response to Yang et al.

PMID- 25853198
TI  - Is polyethylene glycol superior to miralax-gatorade in bowel preparations for
      colonoscopy?

PMID- 25853199
TI  - Response to Zhang.

PMID- 25853200
TI  - Response to Marasco et al.

PMID- 25853201
TI  - Dysbiosis in Celiac disease patients with persistent symptoms on gluten-free
      diet: a condition similar to that present in irritable bowel syndrome patients?

PMID- 25853202
TI  - Focal liver lesions suspected of being cholangiocarcinomas.

PMID- 25853203
TI  - Response to Zanini et al.

PMID- 25853204
TI  - Frozen encapsulated stool in recurrent Clostridium difficile: exploring the role
      of pills in the treatment hierarchy of fecal microbiota transplant nonresponders.

PMID- 25853205
TI  - Assessment of sexual function among inflammatory bowel disease patients.

PMID- 25853206
TI  - A rare case of rapid patency capsule disintegration.

PMID- 25853207
TI  - Serial fecal microbiota transplantation alters mucosal gene expression in
      pediatric ulcerative colitis.

PMID- 25853209
TI  - Corrigendum: quality indicators for ERCP.

PMID- 25853210
TI  - Corrigendum: methotrexate in chronic active Crohn's disease: a double-blind,
      randomized, israeli multicenter trial.

PMID- 25853211
TI  - Corrigendum: development of the NIH Patient-Reported Outcomes Measurement
      Information System (PROMIS) gastrointestinal symptom scales.

PMID- 25853213
TI  - Synthesis of substituted dihydrobenzofurans via tandem S(N)Ar/5-exo-trig
      cyclization.
AB  - A tandem SNAr/5-exo-trig cyclization reaction is reported that converts N-alkyl-
      and -arylimines derived from o-fluorobenzaldehydes into 3-amino-2,3-dihydro-2,2
      diarylbenzofurans in moderate to good yields. Diarylmethoxide coupling partners
      serve the dual role of nucleophile in the SNAr step and catalytic base in the
      cyclization step. With a subset of the substrates, a further base-induced
      elimination of the 3-amino-2,3-dihydro-2,2-diarylbenzofuran to a phenolic enamine
      was observed. 

PMID- 25853214
TI  - Development of a Hybrid Tracer for SPECT and Optical Imaging of Bacterial
      Infections.
AB  - In trauma and orthopedic surgery, infection of implants has a major impact on the
      outcome for patients. Infections may develop either during the initial
      implantation or during the lifetime of an implant. Both infections, as well as
      aseptic loosening of the implant, are reasons for revision of the implants.
      Therefore, discrimination between aseptic-mechanical-loosening and septic
      bacterial-loosening of implants is critical during selection of a patient
      tailored treatment policy. Specific detection and visualization of infections is
      a challenge because it is difficult to discriminate infections from inflammation.
      An imaging tracer that facilitates bacterial identification in a pre- and
      intraoperative setting may aid the workup for patients suspicious of bacterial
      infections. In this study we evaluated an antimicrobial peptide conjugated to a
      hybrid label, which contains both a radioisotope and a fluorescent dye. After
      synthesis of DTPA-Cy5-UBI29-41 and-when necessary-radiolabeling with (111)In
      (yield 96.3 +/- 2.7%), in vitro binding to various bacterial strains was
      evaluated using radioactivity counting and confocal fluorescence microscopy.
      Intramuscular bacterial infections (S. aureus or K. pneumoniae) were also
      visualized in vivo using a combined nuclear and fluorescence imaging system. The
      indium-111 was chosen as label as it has a well-defined coordination chemistry,
      and in pilot studies labeling DTPA-Cy5-UBI29-41 with technetium-99m, we
      encountered damage to the Cy5 dye after the reduction with SnCl2. As a reference,
      we used the validated tracer (99m)Tc-UBI29-41. Fast renal excretion of (111)In
      DTPA-Cy5-UBI29-41 was observed. Target to nontarget (T/NT) ratios were highest at
      2 h post injection: radioactivity counting yielded T/NT ratios of 2.82 +/- 0.32
      for S. aureus and 2.37 +/- 0.05 for K. pneumoniae. Comparable T/NT ratios with
      fluorescence imaging of 2.38 +/- 0.09 for S. aureus and 3.55 +/- 0.31 for K.
      pneumoniae were calculated. Ex vivo confocal microscopy of excised infected
      tissues showed specific binding of the tracer to bacteria. Using a combination of
      nuclear and fluorescence imaging techniques, the hybrid antimicrobial peptide
      conjugate DTPA-Cy5-UBI29-41 was shown to specifically accumulate in bacterial
      infections. This hybrid tracer may facilitate integration of noninvasive
      identification of infections and their extent as well as real-time fluorescence
      guidance during surgical resection of infected areas. 

PMID- 25853215
TI  - Comes Digital Pathology.

PMID- 25853216
TI  - Association between small for gestational age and intrauterine fetal death:
      comparing a customized South Korean growth standard versus a population-based
      fetal growth chart.
AB  - OBJECTIVE: To determine if a customized growth standard developed for an
      ethnically homogeneous South Korean population is better at identifying (SGA)
      fetuses at risk for intra-uterine fetal death (IUFD), compared with a current
      population based-growth standard. STUDY DESIGN: A retrospective cohort study
      comparing the identification of SGA fetuses at risk for IUFD using a customized
      versus a population based-chart. The association between a SGA infant defined as
      a birth weight <10th percentile using the South Korean population chart versus
      the customized chart and IUFD were compared. Intrauterine fetal death was defined
      as fetal demise occurring after 20 weeks gestation. Statistical analyses
      including OR, 95% confidence interval (CI), and screening accuracy using each
      chart were performed. RESULTS: The customized singleton chart identified 11
      (8.2%) of the SGA pregnancies detected by the population chart and classified 15
      additional fetuses as SGA. Those identified as SGA using the customized chart had
      an OR for IUFD that was approximately 15 times as high as those identified using
      the population chart. The customized chart also showed a higher sensitivity and
      specificity for identifying SGA pregnancies at risk for IUFD. CONCLUSION: In this
      ethnically homogenous population, the customized growth chart showed improved
      discrimination in identifying SGA pregnancies at risk for fetal death than the
      population-based growth chart.

PMID- 25853217
TI  - Human ACAP2 is a homolog of C. elegans CNT-1 that promotes apoptosis in cancer
      cells.
AB  - Activation of caspases is an integral part of the apoptotic cell death program.
      Collectively, these proteases target hundreds of substrates, leading to the
      hypothesis that apoptosis is "death by a thousand cuts". Recent work, however,
      has demonstrated that caspase cleavage of only a subset of these substrates
      directs apoptosis in the cell. One such example is C. elegans CNT-1, which is
      cleaved by CED-3 to generate a truncated form, tCNT-1, that acquires a potent
      phosphoinositide-binding activity and translocates to the plasma membrane where
      it inactivates AKT survival signaling. We report here that ACAP2, a homolog of C.
      elegans CNT-1, has a pro-apoptotic function and an identical phosphoinositide
      binding pattern to that of tCNT-1, despite not being an apparent target of
      caspase cleavage. We show that knockdown of ACAP2 blocks apoptosis in cancer
      cells in response to the chemotherapeutic antimetabolite 5-fluorouracil and that
      ACAP2 expression is down-regulated in some esophageal cancers, leukemias and
      lymphomas. These results suggest that ACAP2 is a functional homolog of C. elegans
      CNT-1 and its inactivation or downregulation in human cells may contribute to
      cancer development. 

PMID- 25853218
TI  - In vitro evaluation of genotoxic effects under magnetic resonant coupling
      wireless power transfer.
AB  - Wireless power transfer (WPT) technology using the resonant coupling phenomenon
      has been widely studied, but there are very few studies concerning the possible
      relationship between WPT exposure and human health. In this study, we
      investigated whether exposure to magnetic resonant coupling WPT has genotoxic
      effects on WI38VA13 subcloned 2RA human fibroblast cells. WPT exposure was
      performed using a helical coil-based exposure system designed to transfer power
      with 85.4% efficiency at a 12.5-MHz resonant frequency. The magnetic field at the
      positions of the cell culture dishes is approximately twice the reference level
      for occupational exposure as stated in the International Commission on Non
      Ionizing Radiation Protection (ICNIRP) guidelines. The specific absorption rate
      at the positions of the cell culture dishes matches the respective reference
      levels stated in the ICNIRP guidelines. For assessment of genotoxicity, we
      studied cell growth, cell cycle distribution, DNA strand breaks using the comet
      assay, micronucleus formation, and hypoxanthine-guanine phosphoribosyltransferase
      (HPRT) gene mutation, and did not detect any significant effects between the WPT
      exposed cells and control cells. Our results suggest that WPT exposure under the
      conditions of the ICNIRP guidelines does not cause detectable cellular
      genotoxicity. 

PMID- 25853219
TI  - Healthy vinton: a health impact assessment focused on water and sanitation in a
      small rural town on the US-Mexico border.
AB  - We conducted a Health Impact Assessment (HIA) focused on water and sanitation in
      Vinton, TX, a small rural town on the U.S./Mexico Border. We present the Vinton
      HIA as a case study to inform the practice of HIA in rural limited resource
      communities with higher than average levels of unemployment and poverty, and
      limited infrastructure. Household surveys, focus groups, and interviews provided
      quantitative and qualitative data on water sources and quality, sanitation
      practices, and community health. We found that some of the current water sources
      in Vinton did not meet drinking water standards for total dissolved solids and
      arsenic; the majority of septic tanks were not managed properly; and there was a
      short-term risk of water scarcity due to prolonged drought in the region.
      Prevalent ailments reported by participants included stomach problems, diarrhea,
      and skin problems. These ailments can be related to arsenic and/or biological
      organisms in water. The positive direct and indirect health impacts of improved
      water and sanitation in Vinton included: reduced gastrointestinal illnesses and
      skin disorders; improved water quality, quantity, and pressure; reduced risks
      from failing septic systems; increased property value; potential economic growth;
      and enhanced quality of life. The negative direct and indirect impacts included:
      residents' initial and monthly costs; increased property taxes; increased debt by
      local government; and the need for ongoing support from changing elected decision
      makers. The unique challenges in completing this HIA included: (a) limited
      available data; (b) a culture of fear and distrust among residents; (c)
      residents' lack of education, awareness, and civic discourse regarding water and
      sanitation issues and their impact on public health; and (d) lack of civic
      discourse and participation in the democratic process. An important outcome of
      the HIA was the characterization of local water supplies, which motivated and
      empowered the community members to become more involved in civic discourse
      concerning their water supplies. Results are transferable to similar low-income
      rural communities worldwide where residents are lacking in information about
      their water supplies and in political "voice". 

PMID- 25853220
TI  - Dual-gated topological insulator thin-film device for efficient Fermi-level
      tuning.
AB  - Observations of novel quantum phenomena expected for three-dimensional
      topological insulators (TIs) often require fabrications of thin-film devices and
      tuning of the Fermi level across the Dirac point. Since thin films have both top
      and bottom surfaces, an effective control of the surface chemical potential
      requires dual gating. However, a reliable dual-gating technique for TI thin films
      has not yet been developed. Here we report a comprehensive method to fabricate a
      dual-gated TI device and demonstrate tuning of the chemical potential of both
      surfaces across the Dirac points. The most important part of our method is the
      recipe for safely detaching high-quality, bulk-insulating (Bi(1-x)Sb(x))2Te3 thin
      films from sapphire substrates and transferring them to Si/SiO2 wafers that allow
      back gating. Fabrication of an efficient top gate by low-temperature deposition
      of a SiN(x) dielectric complements the procedure. Our dual-gated devices are
      shown to be effective in tuning the chemical potential in a wide range
      encompassing the Dirac points on both surfaces.

PMID- 25853223
TI  - Modelling catheter-vein biomechanical interactions during an intravenous
      procedure.
AB  - A reliable intravenous (IV) access into the upper extremity veins requires the
      insertion of a temporary short peripheral catheter (SPC). This so common
      procedure is, however, associated with a risk of developing short peripheral
      catheter thrombophlebitis (SPCT) which causes distress and potentially prolongs
      patient hospitalization. We have developed and studied a biomechanical SPC-vein
      computational model during an IV procedure, and explored the biomechanical
      effects of repeated IV episodes on onset and reoccurrences of SPCT. The model was
      used to determine the effects of different insertion techniques as well as inter
      patient biological variability on the catheter-vein wall contact pressures and
      wall deformations. We found that the maximal pressure exerted upon the vein wall
      was inhomogeneously distributed, and that the bending region was exposed to
      significantly greater pressures and deformations. The maximal exerted contact
      pressure on the inner vein's wall was 2938 Pa. The maximal extent of the SPC
      penetration into the vein wall reached 3.6 MUm, which corresponds to
      approximately 100% of the average height of the inner layer, suggesting local
      squashing of endothelial cells at the contact site. The modelling describes a
      potential biomechanical damage pathway that can explain the reoccurrence of SPCT.

PMID- 25853224
TI  - Children's judgements of social withdrawal behaviours.
AB  - Ding et al. (Brit. J. Dev. Psychol., 2015; 33, 159-173) demonstrated that Chinese
      children discriminate between the three subtypes of social withdrawal: Shyness,
      unsociability, and social avoidance. This commentary on the Ding et al.'s paper
      highlights the need to further explore the following: (1) children's
      understanding of the implications of being shy, unsociable, or socially avoidant,
      including assessing these which we know are associated with outcomes for socially
      withdrawn children; (2) what additional subtypes might exist naturally within the
      Chinese culture; and (3) consider the implications of social withdrawal on
      children's developing social skills. 

PMID- 25853228
TI  - Easy To Synthesize, Robust Organo-osmium Asymmetric Transfer Hydrogenation
      Catalysts.
AB  - Asymmetric transfer hydrogenation (ATH) is an important process in organic
      synthesis for which the Noyori-type Ru(II) catalysts [(arene)Ru(Tsdiamine)] are
      now well established and widely used. We now demonstrate for the first time the
      catalytic activity of the osmium analogues. X-ray crystal structures of the 16
      electron Os(II) catalysts are almost identical to those of Ru(II). Intriguingly
      the precursor complex was isolated as a dichlorido complex with a monodentate
      amine ligand. The Os(II) catalysts are readily synthesised (within 1 h) and
      exhibit excellent enantioselectivity in ATH reactions of ketones.

PMID- 25853229
TI  - Effects of a worksite program to improve the cardiovascular health of female
      health care workers.
AB  - PURPOSE: Reducing cardiovascular risk for female health care workers supports
      self-care and facilitates a culture of health promotion. We examined the effect
      of individualized motivational communications on risk and measured program
      participation at a busy hospital, utilizing cardiac rehabilitation resources.
      METHODS: Women (40-65 years old) who self-identified as having increased
      cardiovascular risk and ready for change were randomly assigned to weekly
      motivational counseling or control. All participants were offered classes
      (weight/diet, stress, exercise, and smoking cessation) and gym access. Physical
      and perceptual measures were recorded before and after the 6-month program to
      measure change. Followup 1 year later measured current weight, stress, and
      physical activity. RESULTS: Participants (n = 57) ranked weight as their greatest
      concern (42%). Compared with control, the intervention group resulted in greater:
      weight loss (7.2 vs 3.8 pounds); stress reduction (6.5 vs 4.7; Cohen stress
      scale); and exercise days per week (1.4 vs 1.2). Differences were not
      statistically significant in this small sample, but all changes consistently
      favored the intervention. Program participation was low, as was participation in
      the 1-year followup, although those responding indicated maintenance or further
      improvement. CONCLUSIONS: These consistent and positive findings are promising
      but only suggestive because of the small sample size. Future studies should focus
      on how to get more buy-in from employees, to help insure persistence toward
      health goals. Study results assisted development of a comprehensive Web-based
      employee wellness motivational program to address the issues of on-site
      participation. Attention to health risks in health care workers remains an
      important area of study.

PMID- 25853230
TI  - Theoretical Analysis of the Relative Significance of Thermodynamic and Kinetic
      Dispersion in the dc and ac Voltammetry of Surface-Confined Molecules.
AB  - Commonly, significant discrepancies are reported in theoretical and experimental
      comparisons of dc voltammograms derived from a monolayer or close to monolayer
      coverage of redox-active surface-confined molecules. For example, broader-than
      predicted voltammetric wave shapes are attributed to the thermodynamic or kinetic
      dispersion derived from distributions in reversible potentials (E(0)) and
      electrode kinetics (k(0)), respectively. The recent availability of
      experimentally estimated distributions of E(0) and k(0) values derived from the
      analysis of data for small numbers of surface-confined modified azurin
      metalloprotein molecules now allows more realistic modeling to be undertaken,
      assuming the same distributions apply under conditions of high surface coverage
      relevant to voltammetric experiments. In this work, modeling based on
      conventional and stochastic kinetic theory is considered, and the computationally
      far more efficient conventional model is shown to be equivalent to the stochastic
      one when large numbers of molecules are present. Perhaps unexpectedly, when
      experimentally determined distributions of E(0) and k(0) are input into the
      model, thermodynamic dispersion is found to be unimportant and only kinetic
      dispersion contributes significantly to the broadening of dc voltammograms.
      Simulations of ac voltammetric experiments lead to the conclusion that the ac
      method, particularly when the analysis of kinetically very sensitive higher-order
      harmonics is undertaken, are far more sensitive to kinetic dispersion than the dc
      method. ac methods are therefore concluded to provide a potentially superior
      strategy for addressing the inverse problem of determining the k(0) distribution
      that could give rise to the apparent anomalies in surface-confined voltammetry. 

PMID- 25853232
TI  - Screening Strategies for Pancreatic Cancer in High-Risk Patients: Opportunities
      to Make a Real Impact But Many Questions and Challenges Still Ahead.

PMID- 25853234
TI  - Remarkably stable chelating bis-N-heterocyclic carbene adducts of phosphorus(i)
      cations.
AB  - A convenient one-pot synthesis of chelating bis-N-heterocyclic carbene-ligated
      P(I) salts is described. The solid state structures of these remarkably stable
      phosphamethine cyanine dyes with various N-alkyl groups and counter-anions are
      reported, and initial reactivity results are discussed. 

PMID- 25853231
TI  - mTORC1 maintains the tumorigenicity of SSEA-4(+) high-grade osteosarcoma.
AB  - Inactivation of p53 and/or Rb pathways restrains osteoblasts from cell-cycle exit
      and terminal differentiation, which underpins osteosarcoma formation coupled with
      dedifferentiation. Recently, the level of p-S6K was shown to independently
      predict the prognosis for osteosarcomas, while the reason behind this is not
      understood. Here we show that in certain high-grade osteosarcomas, immature SSEA
      4(+) tumor cells represent a subset of tumor-initiating cells (TICs) whose pool
      size is maintained by mTORC1 activity. mTORC1 supports not only SSEA-4(+) cell
      self-renewal through S6K but also the regeneration of SSEA-4(+) TICs by SSEA-4(-)
      osteosarcoma cell dedifferentiation. Mechanistically, active mTORC1 is required
      to prevent a likely upregulation of the cell-cycle inhibitor p27 independently of
      p53 or Rb activation, which otherwise effectively drives the terminal
      differentiation of SSEA-4(-) osteosarcoma cells at the expense of
      dedifferentiation. Thus, mTORC1 is shown to critically regulate the retention of
      tumorigenicity versus differentiation in discrete differentiation phases in SSEA
      4(+) TICs and their progeny. 

PMID- 25853235
TI  - We Pledge to Change iPLEDGE.

PMID- 25853236
TI  - A Single-Center, Open-Label, 3-Way Crossover Trial to Determine the
      Pharmacokinetic and Pharmacodynamic Interaction Between Nebivolol and Valsartan
      in Healthy Volunteers at Steady State.
AB  - Combining different classes of antihypertensives is more effective for reducing
      blood pressure (BP) than increasing the dose of monotherapies. The aims of this
      phase I study were to investigate pharmacokinetic and pharmacodynamic
      interactions between nebivolol, a vasodilatory beta1-selective blocker, and
      valsartan, an angiotensin II receptor blocker, and to assess safety and
      tolerability of the combination. This was a single-center, randomized, open
      label, multiple-dose, 3-way crossover trial in 30 healthy adults aged 18-45
      years. Participants were randomized into 1 of 6 treatment sequences (1:1:1:1:1:1)
      consisting of three 7-day treatment periods followed by a 7-day washout. Once
      daily oral treatments comprised nebivolol (20 mg), valsartan (320 mg), and
      nebivolol-valsartan combination (20/320 mg). Outcomes included AUC0-tau,ss,
      Cmax,ss, Tmax,ss, changes in BP, pulse rate, plasma angiotensin II, plasma renin
      activity, 24-hour urinary aldosterone, and adverse events. Steady-state
      pharmacokinetic interactions were observed but deemed not clinically significant.
      Systolic and diastolic BP reduction was significantly greater with nebivolol
      valsartan combination than with either monotherapy. The mean pulse rate
      associated with nebivolol and nebivolol-valsartan treatments was consistently
      lower than that associated with valsartan monotherapy. A sharp increase in mean
      day 7 plasma renin activity and plasma angiotensin II that occurred in valsartan
      treated participants was significantly attenuated with concomitant nebivolol
      administration. Mean 24-hour urine aldosterone at day 7 was substantially
      decreased after combined treatment, as compared with either monotherapy. All
      treatments were safe and well tolerated. In conclusion, nebivolol and valsartan
      coadministration led to greater reductions in BP compared with either
      monotherapy; nebivolol and valsartan lower BP through complementary mechanisms. 

PMID- 25853237
TI  - Low-Molecular-Weight Heparins as Immunomodulators in Dermatology Practice.
AB  - Low-molecular-weight heparins (LMWHs) have some effects on cell proliferation and
      inflammation beyond mere anticoagulation. They have been tried on treatment of a
      few dermatological disorders such as lichen planus, skin wound healing, recurrent
      aphtous stomatitis, chronic urticaria, and contact hypersensitivity. LMWHs are
      generally well-tolerated drugs, rarely can lead to severe reactions. In this
      article, we will review the novel indications of LMWHs in dermatology practice
      and common skin reactions associated with their use.

PMID- 25853238
TI  - A monocrystal graphene domain biosensor array with differential output for real
      time monitoring of glucose and normal saline.
AB  - A biosensor array with differential output based on a monocrystal graphene domain
      is proposed to realize high resolution measurements. The differential output
      structure can eliminate the noise that comes from graphene crystal orientation
      and grain boundary, as well as the fluctuation that comes from the contact
      resistance and experiment process, so as to improve resolution in the lower
      concentration. We have fabricated a high quality monocrystal graphene domain that
      has millimeter size by the chemical vapor deposition method. Two identical
      graphene ribbons that are cut from the same domain are used as field effect
      transistor source-to-drain channels for the reference and the test of
      differential output, respectively. The experimental results show that the source
      to-drain current has a fast response shorter than 0.5 second in glucose, normal
      saline and pH buffer solutions of different concentrations. Sensitivity increases
      exponentially with the increase of concentration of the tested liquid and the
      high resolution range is 0.01-2 wt% in glucose and 0.0009-0.018 wt% in saline,
      and the highest resolutions of glucose and saline are 0.01 wt% and 0.0009 wt%,
      respectively. We have fabricated a 1 * 4 array structure with differential
      outputs that pave the way for rapidly detecting ultra-low concentration of
      analytes. 

PMID- 25853239
TI  - Reduced gaze following and attention to heads when viewing a "live" social scene.
AB  - Social stimuli are known to both attract and direct our attention, but most
      research on social attention has been conducted in highly controlled laboratory
      settings lacking in social context. This study examined the role of social
      context on viewing behaviour of participants whilst they watched a dynamic social
      scene, under three different conditions. In two social groups, participants
      believed they were watching a live webcam of other participants. The socially
      engaged group believed they would later complete a group task with the people in
      the video, whilst the non-engaged group believed they would not meet the people
      in the scene. In a third condition, participants simply free-viewed the same
      video with the knowledge that it was pre-recorded, with no suggestion of a later
      interaction. Results demonstrated that the social context in which the stimulus
      was viewed significantly influenced viewing behaviour. Specifically, participants
      in the social conditions allocated less visual attention towards the heads of the
      actors in the scene and followed their gaze less than those in the free-viewing
      group. These findings suggest that by underestimating the impact of social
      context in social attention, researchers risk coming to inaccurate conclusions
      about how we attend to others in the real world. 

PMID- 25853240
TI  - Associations between renal hyperfiltration and serum alkaline phosphatase.
AB  - Renal hyperfiltration, which is associated with renal injury, occurs in diabetic
      or obese individuals. Serum alkaline phosphatase (ALP) level is also elevated in
      patients with diabetes (DM) or metabolic syndrome (MS), and increased urinary
      excretion of ALP has been demonstrated in patients who have hyperfiltration and
      tubular damage. However, little was investigated about the association between
      hyperfiltration and serum ALP level. A retrospective observational study of the
      21,308 adults in the Korea National Health and Nutrition Examination Survey IV-V
      databases (2008-2011) was performed. Renal hyperfiltration was defined as
      exceeding the age- and sex-specific 97.5th percentile. We divided participants
      into 4 groups according to their estimated glomerular filtration rate (eGFR):
      >120, 90-119, 60-89, and <60 mL/min/1.73 m2. The participants with eGFR >120
      mL/min/1.73 m2 showed the highest risk for MS, in the highest ALP quartiles
      (3.848, 95% CI, 1.876-7.892), compared to the lowest quartile. Similarly, the
      highest risk for DM, in the highest ALP quartiles, was observed in participants
      with eGFR >120 ml/min/1.73 m2 (2.166, 95% CI, 1.084-4.329). ALP quartiles were
      significantly associated with albuminuria in participants with eGFR >= 60
      ml/min/1.73m2. The highest ALP quartile had a 1.631-fold risk elevation for
      albuminuria with adjustment of age and sex. (95% CI, 1.158-2.297, P = 0.005).
      After adjustment, the highest ALP quartile had a 1.624-fold risk elevation, for
      renal hyperfiltration (95% CI, 1.204-2.192, P = 0.002). In addition,
      hyperfiltration was significantly associated with hemoglobin, triglyceride, white
      blood cell count, DM, smoking, and alcohol consumption (P<0.05). The relationship
      between serum ALP and metabolic disorders is stronger in participants with an
      upper-normal range of eGFR. Higher ALP levels are significantly associated with
      renal hyperfiltration in Korean general population. 

PMID- 25853241
TI  - The efficacy of Shugan Jianpi Zhixie therapy for diarrhea-predominant irritable
      bowel syndrome: a meta-analysis of randomized, double-blind, placebo-controlled
      trials.
AB  - BACKGROUND: Shugan Jianpi Zhixie therapy (SJZT) has been widely used to treat
      diarrhea-predominant irritable bowel syndrome (IBS-D), but the results are still
      controversial. A meta-analysis of randomized, double-blind, placebo-controlled
      trials was performed to assess the efficacy and tolerability of SJZT for IBS-D.
      METHODS: The MEDLINE, EMBASE, Cochrane Library, the China National Knowledge
      Infrastructure database, the Chinese Biomedical Literature database and the
      Wanfang database were searched up to June 2014 with no language restrictions.
      Summary estimates, including 95% confidence intervals (CI), were calculated for
      global symptom improvement, abdominal pain improvement, and Symptom Severity
      Scale (BSS) score. RESULTS: Seven trials (N=954) were included. The overall risk
      of bias assessment was low. SJZT showed significant improvement for global
      symptom compared to placebo (RR 1.61; 95% CI 1.24, 2.10; P =0.0004; therapeutic
      gain = 33.0%; number needed to treat (NNT) = 3.0). SJZT was significantly more
      likely to reduce overall BSS score (SMD -0.67; 95% CI -0.94, -0.40; P < 0.00001)
      and improve abdominal pain (RR 4.34; 95% CI 2.64, 7.14; P < 0.00001) than
      placebo. The adverse events of SJZT were no different from those of placebo.
      CONCLUSIONS: This meta-analysis suggests that SJZT is an effective and safe
      therapy option for patients with IBS-D. However, due to the high clinical
      heterogeneity and small sample size of the included trials, further standardized
      preparation, large-scale and rigorously designed trials are needed.

PMID- 25853242
TI  - High sodium and low potassium intake among Italian children: relationship with
      age, body mass and blood pressure.
AB  - BACKGROUND: Hypertension is the leading cause of death in developed countries and
      reduction of salt intake is recommended as a key preventive measure. OBJECTIVE:
      To assess the dietary sodium and potassium intakes in a national sample of
      Italian children and adolescents and to examine their relationships with BMI and
      blood pressure (BP) in the framework of the MINISAL survey, a program supported
      by the Italian Ministry of Health. POPULATION AND METHODS: The study population
      included 1424 healthy subjects (766 boys, 658 girls) aged 6-18 years (mean age:
      10.1+/-2.9) who were consecutively recruited in participating National Health
      Service centers in 10 Italian regions. Electrolyte intake was estimated from 24
      hour urine collections tested for completeness by the concomitant measurement of
      creatinine content. Anthropometric indices and BP were measured with standardized
      procedures. RESULTS: The average estimated sodium intake was 129 mmol (7.4 g of
      salt) per day among boys and 117 mmol (6.7 g of salt) among girls. Ninety-three
      percent of the boys and 89% of the girls had a consumption higher than the
      recommended age-specific standard dietary target. The estimated average daily
      potassium intakes were 39 mmol (1.53 g) and 36 mmol (1.40 g), respectively, over
      96% of the boys and 98% of the girls having a potassium intake lower than the
      recommended adequate intake. The mean sodium/potassium ratio was similar among
      boys and girls (3.5 and 3.4, respectively) and over 3-fold greater than the
      desirable level. Sodium intake was directly related to age, body mass and BP in
      the whole population. CONCLUSIONS: The Italian pediatric population is
      characterized by excessive sodium and deficient potassium intake. These data
      suggest that future campaigns should focus on children and adolescents as a major
      target in the framework of a population strategy of cardiovascular prevention.

PMID- 25853244
TI  - Solar radiation during rewarming from torpor in elephant shrews: supplementation
      or substitution of endogenous heat production?
AB  - Many small mammals bask in the sun during rewarming from heterothermy, but the
      implications of this behaviour for their energy balance remain little understood.
      Specifically, it remains unclear whether solar radiation supplements endogenous
      metabolic thermogenesis (i.e., rewarming occurs through the additive effects of
      internally-produced and external heat), or whether solar radiation reduces the
      energy required to rewarm by substituting (i.e, replacing) metabolic heat
      production. To address this question, we examined patterns of torpor and
      rewarming rates in eastern rock elephant shrews (Elephantulus myurus) housed in
      outdoor cages with access to either natural levels of solar radiation or levels
      that were experimentally reduced by means of shade cloth. We also tested whether
      acclimation to solar radiation availability was manifested via phenotypic
      flexibility in basal metabolic rate (BMR), non-shivering thermogenesis (NST)
      capacity and/or summit metabolism (Msum). Rewarming rates varied significantly
      among treatments, with elephant shrews experiencing natural solar radiation
      levels rewarming faster than conspecifics experiencing solar radiation levels
      equivalent to approximately 20% or 40% of natural levels. BMR differed
      significantly between individuals experiencing natural levels of solar radiation
      and conspecifics experiencing approximately 20% of natural levels, but no between
      treatment difference was evident for NST capacity or Msum. The positive
      relationship between solar radiation availability and rewarming rate, together
      with the absence of acclimation in maximum non-shivering and total heat
      production capacities, suggests that under the conditions of this study solar
      radiation supplemented rather than substituted metabolic thermogenesis as a
      source of heat during rewarming from heterothermy. 

PMID- 25853243
TI  - Lysosomal trafficking of TGFBIp via caveolae-mediated endocytosis.
AB  - Transforming growth factor-beta-induced protein (TGFBIp) is ubiquitously
      expressed in the extracellular matrix (ECM) of various tissues and cell lines.
      Progressive accumulation of mutant TGFBIp is directly involved in the
      pathogenesis of TGFBI-linked corneal dystrophy. Recent studies reported that
      mutant TGFBIp accumulates in cells; however, the trafficking of TGFBIp is poorly
      understood. Therefore, we investigated TGFBIp trafficking to determine the route
      of its internalization and secretion and to elucidate its roles in the
      pathogenesis of granular corneal dystrophy type 2 (GCD2). Our data indicate that
      newly synthesized TGFBIp was secreted via the endoplasmic reticulum/Golgi
      dependent secretory pathway, and this secretion was delayed in the corneal
      fibroblasts of patients with GCD2. We also found that TGFBIp was internalized by
      caveolae-mediated endocytosis, and the internalized TGFBIp accumulated after
      treatment with bafilomycin A1, an inhibitor of lysosomal degradation. In
      addition, the proteasome inhibitor MG132 inhibits the endocytosis of TGFBIp. Co
      immunoprecipitation revealed that TGFBIp interacted with integrin alphaVbeta3.
      Moreover, treatment with arginine-glycine-aspartic acid (RGD) tripeptide
      suppressed the internalization of TGFBIp. These insights on TGFBIp trafficking
      could lead to the identification of novel targets and the development of new
      therapies for TGFBI-linked corneal dystrophy. 

PMID- 25853245
TI  - Behaviour and locomotor activity of a migratory catostomid during fishway
      passage.
AB  - Fishways have been developed to restore longitudinal connectivity in rivers.
      Despite their potential for aiding fish passage, fishways may represent a source
      of significant energetic expenditure for fish as they are highly turbulent
      environments. Nonetheless, our understanding of the physiological mechanisms
      underpinning fishway passage of fish is still limited. We examined swimming
      behaviour and activity of silver redhorse (Moxostoma anisurum) during its upriver
      spawning migration in a vertical slot fishway. We used an accelerometer-derived
      instantaneous activity metric (overall dynamic body acceleration) to estimate
      location-specific swimming activity. Silver redhorse demonstrated progressive
      increases in activity during upstream fishway passage. Moreover, location
      specific passage duration decreased with an increasing number of passage
      attempts. Turning basins and the most upstream basin were found to delay fish
      passage. No relationship was found between basin-specific passage duration and
      activity and the respective values from previous basins. The results demonstrate
      that successful fishway passage requires periods of high activity. The resultant
      energetic expenditure may affect fitness, foraging behaviour and increase
      susceptibility to predation, compromising population sustainability. This study
      highlights the need to understand the physiological mechanisms underpinning
      fishway passage to improve future designs and interpretation of biological
      evaluations. 

PMID- 25853246
TI  - Health service utilization for mental, behavioural and emotional problems among
      conflict-affected population in Georgia: a cross-sectional study.
AB  - BACKGROUND: There is large gap in mental illness treatment globally and
      potentially especially so in war-affected populations. The study aim was to
      examine health care utilization patterns for mental, behavioural and emotional
      problems among the war-affected adult population in the Republic of Georgia.
      METHODS: A cross-sectional household survey was conducted among 3600 adults
      affected by 1990s and 2008 armed conflicts in Georgia. Service use was measured
      for the last 12 months for any mental, emotional or behavioural problems. TSQ,
      PHQ-9 and GAD-7 were used to measure current symptoms of PTSD, depression and
      anxiety. Descriptive and regression analyses were used. RESULTS: Respondents were
      predominantly female (65.0%), 35.8% were unemployed, and 56.0% covered by the
      government insurance scheme. From the total sample, 30.5% had symptoms of at
      least one current mental disorder. Among them, 39.0% sought care for mental
      problems, while 33.1% expressed facing barriers to accessing care and so did not
      seek care. General practitioners (29%) and neurologists (26%) were consulted by
      the majority of those with a current mental disorder who accessed services, while
      use of psychiatric services was far more limited. Pharmacotherapy was the
      predominant type of care (90%). Female gender (OR 1.50, 95% CI: 1.25, 1.80),
      middle-age (OR 1.83, 95% CI: 1.48, 2.26) and older-age (OR 1.62, 95% CI: 1.19,
      2.21), possession of the state insurance coverage (OR 1.55, 95% CI: 1.30, 1.86),
      current PTSD symptoms (OR 1.56, 95% CI: 1.29, 1.90) and depression (OR 2.12, 95%
      CI: 1.70, 2.65) were associated with higher rates of health service utilization,
      while employed were less likely to use services (OR 0.71, 95% CI: 0.55, 0.89).
      CONCLUSIONS: Reducing financial access barriers and increasing awareness and
      access to local care required to help reduce the burden of mental disorders among
      conflict-affected persons in Georgia.

PMID- 25853248
TI  - Correction: Hexon modification to improve the activity of oncolytic adenovirus
      vectors against neoplastic and stromal cells in pancreatic cancer.

PMID- 25853247
TI  - Corneal confocal microscopy detects neuropathy in patients with type 1 diabetes
      without retinopathy or microalbuminuria.
AB  - OBJECTIVE: Corneal innervation is increasingly used as a surrogate marker of
      human diabetic peripheral neuropathy (DPN) however its temporal relationship with
      the other microvascular complications of diabetes is not fully established. In
      this cross-sectional, observational study we aimed to assess whether neuropathy
      occurred in patients with type 1 diabetes, without retinopathy or
      microalbuminuria. MATERIALS AND METHODS: All participants underwent detailed
      assessment of peripheral neuropathy [neuropathy disability score (NDS), vibration
      perception threshold (VPT), peroneal motor nerve conduction velocity (PMNCV),
      sural sensory nerve conduction velocity (SSNCV) and in vivo corneal confocal
      microscopy (IVCCM)], retinopathy (digital fundus photography) and albuminuria
      status [albumin: creatinine ratio (ACR)]. RESULTS: 53 patients with Type 1
      diabetes with (n=37) and without retinopathy (n=16) were compared to control
      subjects (n=27). SSNCV, corneal nerve fibre (CNFD) and branch (CNBD) density and
      length (CNFL) were reduced significantly (p<0.001) in diabetic patients without
      retinopathy compared to control subjects. Furthermore, CNFD, CNBD and CNFL were
      also significantly (p<0.001) reduced in diabetic patients without
      microalbuminuria (n=39), compared to control subjects. Greater neuropathic
      severity was associated with established retinopathy and microalbuminuria.
      CONCLUSIONS: IVCCM detects early small fibre damage in the absence of retinopathy
      or microalbuminuria in patients with Type 1 diabetes.

PMID- 25853250
TI  - An observational study examining the relationship between respiratory symptoms,
      airway inflammation and bacteriology in children with severe neurodisability.
AB  - BACKGROUND: Children with severe neurodisability (ND) commonly suffer from
      chronic respiratory symptoms that impact greatly on quality of life, and lead to
      recurrent hospital admissions. This morbidity (and its causes) is poorly
      described, despite being well recognised by paediatricians. In this study, we
      characterised respiratory symptoms in children with ND at times of stability and
      deterioration. We also assessed the relationship between respiratory symptoms,
      lower airway inflammatory markers and levels of infection/colonisation. METHODS:
      ND children were recruited upon admission for elective surgery (Elective-ND [n =
      16]), or acutely upon admission to Intensive Care (PICU-ND [n = 19]), and
      compared to healthy control children [n = 12]. Parents completed a validated
      respiratory symptom questionnaire in which symptoms associated with activity were
      removed (total maximal score of 108). Bronchoalveolar lavage (BAL) was collected,
      and BAL neutrophil counts, IL-8 and TGFbeta-1 levels measured. BAL microbial
      analysis was performed using a 16S/18S rRNA gene based assay and Pseudomonas
      aeruginosa PCR. RESULTS: All ND children had high levels of respiratory symptoms
      (median [IQR] symptom score PICU-ND, 55[38-64]; Elective-ND, 26[7-45]; Control,
      4[0-7]: p<0.01), which affected their families, particularly at nighttime.
      Elective-ND patients with a total respiratory symptom score >20 invariably had
      BAL neutrophilia. Elective patients with 16S/18S microbial rDNA positive BAL had
      higher neutrophil counts (positive, 33[18-70]%; negative, 8[4-38]%: p<0.05) and
      generally higher symptom scores (positive, 17[5-32]; negative, 5[0-9]: p =
      0.097). Streptococcus mitis was commonly identified in BAL from ND children;
      Pseudomonas aeruginosa was not identified in any sample. CONCLUSIONS: Children
      with severe ND often have high levels of chronic respiratory symptoms, which may
      relate to lower airway inflammation. Bacterial airway colonisation, particularly
      with oral commensals, may play a role in both symptom generation and
      inflammation.

PMID- 25853251
TI  - The palaeoenvironmental impact of prehistoric settlement and proto-historic
      urbanism: tracing the emergence of the Oppidum of Corent, Auvergne, France.
AB  - Early human societies and their interactions with the natural world have been
      extensively explored in palaeoenvironmental studies across Central and Western
      Europe. Yet, despite an extensive body of scholarship, there is little
      consideration of the environmental impacts of proto-historic urbanisation.
      Typically palaeoenvironmental studies of Bronze and Iron Age societies discuss
      human impact in terms of woodland clearance, landscape openness and evidence for
      agriculture. Although these features are clearly key indicators of human
      settlement, and characterise Neolithic and early to Middle Bronze Age impacts at
      Corent, they do not appear to represent defining features of a protohistoric
      urban environment. The Late Iron Age Gallic Oppidum of Corent is remarkable for
      the paucity of evidence for agriculture and strong representation of apophytes
      associated with disturbance. Increased floristic diversity - a phenomenon also
      observed in more recent urban environments - was also noted. The same, although
      somewhat more pronounced, patterns are noted for the Late Bronze Age and hint at
      the possibility of a nascent urban area. High percentages of pollen from non
      native trees such as Platanus, Castanea and Juglans in the late Bronze Age and
      Gallic period also suggest trade and cultural exchange, notably with the
      Mediterranean world. Indeed, these findings question the validity of applying
      Castanea and Juglans as absolute chronological markers of Romanisation. These
      results clearly indicate the value of local-scale palaeoecological studies and
      their potential for tracing the phases in the emergence of a proto-historic urban
      environment. 

PMID- 25853249
TI  - Is that me or my twin? Lack of self-face recognition advantage in identical
      twins.
AB  - Despite the increasing interest in twin studies and the stunning amount of
      research on face recognition, the ability of adult identical twins to
      discriminate their own faces from those of their co-twins has been scarcely
      investigated. One's own face is the most distinctive feature of the bodily self,
      and people typically show a clear advantage in recognizing their own face even
      more than other very familiar identities. Given the very high level of
      resemblance of their faces, monozygotic twins represent a unique model for
      exploring self-face processing. Herein we examined the ability of monozygotic
      twins to distinguish their own face from the face of their co-twin and of a
      highly familiar individual. Results show that twins equally recognize their own
      face and their twin's face. This lack of self-face advantage was negatively
      predicted by how much they felt physically similar to their co-twin and by their
      anxious or avoidant attachment style. We speculate that in monozygotic twins, the
      visual representation of the self-face overlaps with that of the co-twin. Thus,
      to distinguish the self from the co-twin, monozygotic twins have to rely much
      more than control participants on the multisensory integration processes upon
      which the sense of bodily self is based. Moreover, in keeping with the notion
      that attachment style influences perception of self and significant others, we
      propose that the observed self/co-twin confusion may depend upon insecure
      attachment. 

PMID- 25853252
TI  - Both fasting and glucose-stimulated proinsulin levels predict hyperglycemia and
      incident type 2 diabetes: a population-based study of 9,396 Finnish men.
AB  - BACKGROUND: Hyperproinsulinemia is an indicator of beta-cell dysfunction, and
      fasting proinsulin levels are elevated in patients with hyperglycemia. It is not
      known whether proinsulin levels after a glucose load are better predictors of
      hyperglycemia and type 2 diabetes than fasting proinsulin. METHODS: Participants
      were 9,396 Finnish men (mean+/-SD, age 57.3+/-7.1 years, BMI 27.0+/-4.0 kg/m2) of
      the population-based METabolic Syndrome In Men Study who were non-diabetic at the
      recruitment, and who participated in a 6-year follow-up study. Proinsulin and
      insulin levels were measured in the fasting state and 30 and 120 min after an
      oral glucose load. Area under the curve (AUC) and proinsulin to insulin ratios
      were calculated. RESULTS: Fasting proinsulin, proinsulin at 30 min and proinsulin
      AUC during the first 30 min of an oral glucose tolerance test significantly
      predicted both the worsening of hyperglycemia and type 2 diabetes after
      adjustment for confounding factors. Further adjustment for insulin sensitivity
      (Matsuda index) or insulin secretion (Disposition index) weakened these
      associations. Insulin sensitivity had a major impact on these associations.
      CONCLUSION: Our results suggest that proinsulin in the fasting state and after an
      oral glucose load similarly predict the worsening of hyperglycemia and conversion
      to type 2 diabetes.

PMID- 25853253
TI  - Features of the retinotopic representation in the visual wulst of a laterally
      eyed bird, the zebra finch (Taeniopygia guttata).
AB  - The visual wulst of the zebra finch comprises at least two retinotopic maps of
      the contralateral eye. As yet, it is not known how much of the visual field is
      represented in the wulst neuronal maps, how the organization of the maps is
      related to the retinal architecture, and how information from the ipsilateral eye
      is involved in the activation of the wulst. Here, we have used autofluorescent
      flavoprotein imaging and classical anatomical methods to investigate such
      characteristics of the most posterior map of the multiple retinotopic
      representations. We found that the visual wulst can be activated by visual
      stimuli from a large part of the visual field of the contralateral eye.
      Horizontally, the visual field representation extended from -5 degrees  beyond
      the beak tip up to +125 degrees  laterally. Vertically, a small strip from -10
      degrees  below to about +25 degrees  above the horizon activated the visual
      wulst. Although retinal ganglion cells had a much higher density around the fovea
      and along a strip extending from the fovea towards the beak tip, these areas were
      not overrepresented in the wulst map. The wulst area activated from the foveal
      region of the ipsilateral eye, overlapped substantially with the middle of the
      three contralaterally activated regions in the visual wulst, and partially with
      the other two. Visual wulst activity evoked by stimulation of the frontal visual
      field was stronger with contralateral than with binocular stimulation. This
      confirms earlier electrophysiological studies indicating an inhibitory influence
      of the activation of the ipsilateral eye on wulst activity elicited by
      stimulating the contralateral eye. The lack of a foveal overrepresentation
      suggests that identification of objects may not be the primary task of the zebra
      finch visual wulst. Instead, this brain area may be involved in the processing of
      visual information necessary for spatial orientation. 

PMID- 25853254
TI  - Molecular detection of Leishmania in phlebotomine sand flies (Diptera:
      Psychodidae) from a cutaneous leishmaniasis focus atXakriaba Indigenous Reserve,
      Brazil.
AB  - Autochthonous cases of American cutaneous leishmaniasis (ACL) have been reported
      since 2001 in the Xakriaba Indigenous Reserve located in the municipality of Sao
      Joao das Missoes in northern Minas Gerais state, Brazil. In order to study the
      presence of Leishmania DNA in phlebotomine sand flies, six entomological
      collections were carried out from July 2008 through July 2009, using 40 light
      traps placed in peridomicile areas of 20 randomly selected houses. From October
      2011 through August 2012, another six collections were carried out with 20 light
      traps distributed among four trails (five traps per trail) selected for a
      previous study of wild and synanthropic hosts of Leishmania. A total of 4,760
      phlebotomine specimens were collected belonging to ten genera and twenty-three
      species. Single female specimens or pools with up to ten specimens of the same
      locality, species and date, for Leishmania detection by molecular methods.
      Species identification of parasites was performed with ITS1 PCR-RFLP using HaeIII
      enzyme and genetic sequencing for SSU rRNA target. The presence of Leishmania DNA
      was detected in eleven samples from peridomicile areas: Lu. longipalpis (two),
      Nyssomyia intermedia (four), Lu. renei (two), Lu. ischnacantha, Micropygomyia
      goiana and Evandromyia lenti (one pool of each specie). The presence of
      Leishmania DNA was detected in twelve samples from among the trails: Martinsmyia
      minasensis (six), Ny. intermedia (three), Mi. peresi (two) and Ev. lenti (one).
      The presence of Leishmania infantum DNA in Lu. longipalpis and Leishmania
      braziliensis DNA in Ny. intermediasupport the epidemiological importance of these
      species of sand flies in the cycle of visceral and cutaneous leishmaniasis,
      respectively. The results also found other species associated with Leishmania
      DNA, such as Mt. minasensis and Ev. lenti, which may participate in a wild and/or
      synanthropic cycle of Leishmania transmission in the studied area. 

PMID- 25853255
TI  - Ciprofloxacin-eluting nanofibers inhibits biofilm formation by Pseudomonas
      aeruginosa and a methicillin-resistant Staphylococcus aureus.
AB  - Pseudomonas aeruginosa and Staphylococcus aureus are commonly associated with
      hospital-acquired infections and are known to form biofilms. Ciprofloxacin (CIP),
      which is normally used to treat these infections, is seldom effective in killing
      cells in a biofilm. This is mostly due to slow or weak penetration of CIP to the
      core of biofilms. The problem is accentuated by the release of CIP below MIC
      (minimal inhibitory concentration) levels following a rapid (burst) release. The
      aim of this study was to develop a drug carrier that would keep CIP above MIC
      levels for an extended period. Ciprofloxacin was suspended into poly(D,L-lactide)
      (PDLLA) and poly(ethylene oxide) (PEO), and electrospun into nanofibers (CIP-F).
      All of the CIP was released from the nanofibers within 2 h, which is typical of a
      burst release. However, 99% of P. aeruginosa PA01 cells and 91% of S. aureus Xen
      30 cells (a methicillin-resistant strain) in biofilms were killed when exposed to
      CIP-F. CIP levels remained above MIC for 5 days, as shown by growth inhibition of
      the cells in vitro. The nanofibers were smooth in texture with no bead formation,
      as revealed by scanning electron and atomic force microscopy. A single vibration
      peak at 1632 cm-1, recorded with Fourier transform infrared spectroscopy,
      indicated that CIP remained in crystal form when incorporated into PDLLA: PEO. No
      abnormalities in the histology of MCF-12A breast epithelial cells were observed
      when exposed to CIP-F. This is the first report of the inhibition of biofilm
      formation by CIP released from PDLLA: PEO nanofibers. 

PMID- 25853256
TI  - Informational needs and the quality of life of patients in their first year after
      metastatic breast cancer diagnosis.
AB  - BACKGROUND: Little is known about the informational needs and quality of life
      (QOL) of patients with metastatic breast cancer (MBC) within the first year of
      their diagnosis. OBJECTIVES: To describe the informational needs and QOL of
      patients with MBC within the first year of diagnosis, and to identify
      sociodemographic and medical factors that may be associated with informational
      needs and QOL. METHODS: 52 patients (50 women, 2 men) enrolled within a year of
      diagnosis of MBC completed a cross-sectional, self-administered paper survey that
      included patient demographics, the Toronto Informational Needs Questionnaire
      Breast Cancer (TINQ), the Hospital Anxiety and Depression Scale (HADS), and
      Medical Outcomes Study Short Form-36 (SF-36). High informational need was defined
      as a TINQ score of >= 200. RESULTS: Of the total 52 patients, 69% (35/52) had
      high informational needs, 20% met the criteria for anxiety (HADS-Anxiety score,
      >= 11), and 8% met the criteria for depression. SF-36 scores were lower in all 8
      subscales compared with the general population. Multivariate analyses showed that
      patients who were married or living as married (OR, 6.1; 95% CI, 1.4-28.9) and
      patients with de novo MBC (OR, 2.8; 95% CI, 0.5-14.3) or a shorter disease-free
      interval (DFI; < 5 years; OR, 24.2; 95% CI, 3.1-187.4) were more likely to have
      more informational needs (C statistic, 0.824) than were patients with a longer
      DFI (>= 5 years). LIMITATIONS: This is a small cross-sectional study of a single
      academic institution. CONCLUSIONS: Patients with recently diagnosed MBC have high
      informational needs and decreased overall QOL. Additional research and supportive
      services meeting the informational and psychosocial needs of patients living with
      MBC are warranted.

PMID- 25853257
TI  - Weight change associated with third-generation adjuvant chemotherapy in breast
      cancer patients.
AB  - BACKGROUND: Studies have shown that breast cancer treatment can cause an increase
      in weight. Weight gain during chemotherapy is usually significant and may be
      associated with poor survival. However, the role of third- generation
      chemotherapy regimens and weight gain is not well reviewed. METHODS: We
      retrospectively analyzed the mean percentage weight change during the first year
      after breast cancer diagnosis in 246 patients at West Virginia University during
      September 2007 and October 2010. Kruskal-Wallis test and post hoc pairwise
      comparisons were used to assess the influence of age, histology, stage,
      ER/PR/HER2/neu status, menopausal status, and types of therapeutic modalities
      received on the percentage weight change. Kaplan-Meier method with log-rank test
      was used to evaluate recurrence-free survival (RFS). Local or distant recurrence
      and disease progression were events for RFS analysis and disease-free patients
      were censored at last follow-up. RESULTS: Mean weight gain was 0.39% (SD, 0.40)
      of baseline body weight, 1 year after diagnosis of breast cancer. Premenopausal
      status was the only factor associated with significant weight gain (+1.67% vs 
      0.10% for postmenopausal patients; P = .02). Stages >= III was associated with
      significant weight loss (-1.64% for stages III, IV vs +0.85% for stages 0, I, II;
      P = .02) and a lower RFS at 3 years and 5 years (P < .0001). Higher baseline
      weight (> 90th percentile) did not have any significant impact on RFS (0.84 vs
      0.91; P = .19). There was no significant change in weight relative to other
      factors. CONCLUSIONS: Our study in patients receiving third-generation adjuvant
      chemotherapy regimens did not show any significant change in percentage weight
      with chemotherapy. Premenopausal status was the only significant factor
      associated with weight gain. As expected, stage III or higher disease was
      associated with significant weight loss and lower RFS.

PMID- 25853258
TI  - Quality of supportive care for patients with advanced lung cancer in the Veterans
      Health Administration.
AB  - BACKGROUND: Morbidity related to cancer and its treatment remains a significant
      source of human suffering and a challenge to the delivery of high-quality care.
      OBJECTIVES: To develop and apply quality indicators to evaluate quality of
      supportive care for advanced lung cancer in the Veterans Health Administration
      (VHA) and examine facility-level predictors of quality. METHODS: We evaluated
      supportive care quality using 12 quality indicators. Data were taken from VHA
      electronic health records for incident lung cancer cases occurring during 2007.
      Organizational characteristics of 111 VHA facilities were examined for
      association with receipt of care. LIMITATIONS: Not all supportive care was
      evaluated. Care processes identified as present at facilities may not have been
      applied to cohort patients. Facility-level results may be influenced by errors in
      attributing a patient's care to the correct facility. CONCLUSIONS: Quality
      indicators for supportive cancer care can be developed and applied in large
      evaluations using electronic health record review. This study confirmed high
      quality supportive care, while identifying significant facility-level variation
      in VHA.

PMID- 25853259
TI  - Patient and provider concordance on symptoms during the oncology outpatient
      clinic visit.
AB  - BACKGROUND: Cancer patients experience multiple symptoms, with specific symptoms
      varying by cancer type. Problems in communication between patients and health
      care providers (HCPs) can interfere with effective symptom assessment and
      management. OBJECTIVE: To address gaps in previous research by prospectively
      examining concordance between HCPs and patients on identifying patients' symptoms
      by using an identical tool for patients and HCPs at the time of the oncology
      clinic visit. METHODS: 94 patients completed measures of symptom experience and
      medical comorbidities before seeing their oncology medical team. HCPs were
      informed of a patient's participation in the study before seeing the patient in
      clinic. Immediately after the clinic visit, HCPs completed a symptom survey in
      which they noted the patient's symptoms. RESULTS: Patients reported more symptoms
      than the HCPs endorsed. The highest level of concordance for any symptom fell in
      the moderate agreement range. Kappa values reflecting concordance between
      patients and HCPs were not significantly different between the various patient
      HCP pairs. No demographic or clinical variables for patients were found to be
      statistically related to the level of agreement on patients' symptoms.
      LIMITATIONS: The use of a small convenience sample size drawn from 3 specialty
      oncology outpatient clinics may limit the generalizability of the results to
      other types of cancer. The distribution of cancer stage was weighted toward
      stages III and IV, likely contributing to the number of symptoms. CONCLUSIONS:
      The level of agreement between HCPs and oncology patients on patient symptoms is
      weak. Concordance levels were similar, regardless of the type of HCP.

PMID- 25853260
TI  - Breast cancer with brain metastases in pregnancy.
AB  - Breast cancer during pregnancy is a therapeutic challenge. Evidence to guide
      management in metastatic breast cancer during pregnancy is limited, mainly
      because of a lack of randomized trials. Care needs to be individualized with
      interdisciplinary collaboration. Various case reports and case series in the
      literature have shown the safety of some chemotherapeutic agents during the
      second and third trimesters of pregnancy. Surgery is also safe after the first
      trimester. Brain metastasis from breast cancer during pregnancy is an especially
      challenging clinical situation and has been reported only in one other case. We
      present the case of a young woman with HER2/neu overexpressed inflammatory breast
      cancer who became pregnant while on treatment, refused termination of pregnancy,
      and developed brain metastasis during the second trimester of pregnancy, posing a
      management dilemma. 

PMID- 25853261
TI  - The WRKY transcription factor genes in eggplant (Solanum melongena L.) and Turkey
      Berry (Solanum torvum Sw.).
AB  - WRKY transcription factors, which play critical roles in stress responses, have
      not been characterized in eggplant or its wild relative, turkey berry. The recent
      availability of RNA-sequencing data provides the opportunity to examine WRKY
      genes from a global perspective. We identified 50 and 62 WRKY genes in eggplant
      (SmelWRKYs) and turkey berry (StorWRKYs), respectively, all of which could be
      classified into three groups (I-III) based on the WRKY protein structure. The
      SmelWRKYs and StorWRKYs contain ~76% and ~95% of the number of WRKYs found in
      other sequenced asterid species, respectively. Positive selection analysis
      revealed that different selection constraints could have affected the evolution
      of these groups. Positively-selected sites were found in Groups IIc and III.
      Branch-specific selection pressure analysis indicated that most WRKY domains from
      SmelWRKYs and StorWRKYs are conserved and have evolved at low rates since their
      divergence. Comparison to homologous WRKY genes in Arabidopsis revealed several
      potential pathogen resistance-related SmelWRKYs and StorWRKYs, providing possible
      candidate genetic resources for improving stress tolerance in eggplant and
      probably other Solanaceae plants. To our knowledge, this is the first report of a
      genome-wide analyses of the SmelWRKYs and StorWRKYs. 

PMID- 25853263
TI  - Serum selenium and ceruloplasmin in nigerians with peripartum cardiomyopathy.
AB  - The study aimed to determine if selenium deficiency, serum ceruloplasmin and
      traditional birth practices are risk factors for peripartum cardiomyopathy
      (PPCM), in Kano, Nigeria. This is a case-control study carried out in three
      hospitals, and PPCM patients were followed up for six months. Critically low
      serum selenium concentration was defined as <70 ug/L. A total of 39 PPCM patients
      and 50 controls were consecutively recruited after satisfying the inclusion
      criteria. Mean serum selenium in patients (61.7 +/- 14.9 ug/L) was significantly
      lower than in controls (118.4 +/- 45.6 ug/L) (p < 0.001). The prevalence of serum
      selenium <70 ug/L was significantly higher among patients (76.9%) than controls
      (22.0%) (p < 0.001). The mean ceruloplasmin and prevalence of socio-economic
      indices, multiparity, pregnancy-induced hypertension, obesity and twin pregnancy
      were not different between the groups (p > 0.05). Logistic regression showed that
      rural residency significantly increased the odds for serum selenium <70 ug/L by
      2.773-fold (p = 0.037). Baseline serum levels of selenium and ceruloplasmin were
      not associated with six-month mortality. This study has shown that selenium
      deficiency is a risk factor for PPCM in Kano, Nigeria, and is related to rural
      residency. However, serum ceruloplasmin, customary birth practices and some other
      characteristics were not associated with PPCM in the study area. 

PMID- 25853262
TI  - Phenotypic and molecular convergence of 2q23.1 deletion syndrome with other
      neurodevelopmental syndromes associated with autism spectrum disorder.
AB  - Roughly 20% of autism spectrum disorders (ASD) are syndromic with a well
      established genetic cause. Studying the genes involved can provide insight into
      the molecular and cellular mechanisms of ASD. 2q23.1 deletion syndrome (causative
      gene, MBD5) is a recently identified genetic neurodevelopmental disorder
      associated with ASD. Mutations in MBD5 have been found in ASD cohorts. In this
      study, we provide a phenotypic update on the prevalent features of 2q23.1
      deletion syndrome, which include severe intellectual disability, seizures,
      significant speech impairment, sleep disturbance, and autistic-like behavioral
      problems. Next, we examined the phenotypic, molecular, and network/pathway
      relationships between nine neurodevelopmental disorders associated with ASD:
      2q23.1 deletion Rett, Angelman, Pitt-Hopkins, 2q23.1 duplication, 5q14.3
      deletion, Kleefstra, Kabuki make-up, and Smith-Magenis syndromes. We show
      phenotypic overlaps consisting of intellectual disability, speech delay,
      seizures, sleep disturbance, hypotonia, and autistic-like behaviors. Molecularly,
      MBD5 possibly regulates the expression of UBE3A, TCF4, MEF2C, EHMT1 and RAI1.
      Network analysis reveals that there could be indirect protein interactions,
      further implicating function for these genes in common pathways. Further, we show
      that when MBD5 and RAI1 are haploinsufficient, they perturb several common
      pathways that are linked to neuronal and behavioral development. These findings
      support further investigations into the molecular and pathway relationships among
      genes linked to neurodevelopmental disorders and ASD, which will hopefully lead
      to common points of regulation that may be targeted toward therapeutic
      intervention. 

PMID- 25853264
TI  - In Utero exposure to low-dose alcohol induces reprogramming of mammary
      development and tumor risk in MMTV-erbB-2 transgenic mice.
AB  - There is increasing evidence that prenatal exposure to environmental factors may
      modify breast cancer risk later in life. This study aimed to investigate the
      effects of in utero exposure to low-dose alcohol on mammary development and tumor
      risk. Pregnant MMTV-erbB-2 mice were exposed to alcohol (6 g/kg/day) between day
      13 and day 19 of gestation, and the female offspring were examined for tumor
      risk. Whole mount analysis indicated that in utero exposure to low-dose alcohol
      induced significant increases in ductal extension at 10 weeks of age. Molecular
      analysis showed that in utero alcohol exposure induced upregulation of ERalpha
      signaling and activation of Akt and Erk1/2 in pubertal mammary glands. However,
      enhanced signaling in the EGFR/erbB-2 pathway appeared to be more prominent in 10
      week-old glands than did signaling in the other pathways. Interestingly, tumor
      development in mice with in utero exposure to low-dose alcohol was slightly
      delayed compared to control mice, but tumor multiplicity was increased. The
      results indicate that in utero exposure to low-dose alcohol induces the
      reprogramming of mammary development by mechanisms that include altered signaling
      in the estrogen receptor (ER) and erbB-2 pathways. The intriguing tumor
      development pattern might be related to alcohol dose and exposure conditions, and
      warrants further investigation. 

PMID- 25853265
TI  - Design of an osteoinductive extracellular fibronectin matrix protein for bone
      tissue engineering.
AB  - Integrin-mediated cell-matrix interactions play an important role in
      osteogenesis. Here, we constructed a novel osteoinductive fibronectin matrix
      protein (oFN) for bone tissue engineering, designed to combine the integrin
      binding modules from fibronectin (iFN) and a strong osteoinductive growth factor,
      bone morphogenetic protein-2. Compared with iFN, the purified oFN matrix protein
      caused a significant increase in cell adhesion and osteogenic differentiation of
      pre-osteoblast MC3T3-E1 cells (p < 0.05). 

PMID- 25853266
TI  - Interactive effects of dietary lipid and phenotypic feed efficiency on the
      expression of nuclear and mitochondrial genes involved in the mitochondrial
      electron transport chain in rainbow trout.
AB  - A 2 * 3 factorial study was conducted to evaluate the effects of dietary lipid
      level on the expression of mitochondrial and nuclear genes involved in electron
      transport chain in all-female rainbow trout Oncorhynchus mykiss. Three practical
      diets with a fixed crude protein content of 40%, formulated to contain 10%
      (40/10), 20% (40/20) and 30% (40/30) dietary lipid, were fed to apparent satiety
      to triplicate groups of either low-feed efficient (F120; 217.66 +/- 2.24 g
      initial average mass) or high-feed efficient (F136; 205.47 +/- 1.27 g) full-sib
      families of fish, twice per day, for 90 days. At the end of the experiment, the
      results showed that there is an interactive effect of the dietary lipid levels
      and the phenotypic feed efficiency (growth rate and feed efficiency) on the
      expression of the mitochondrial genes nd1 (NADH dehydrogenase subunit 1), cytb
      (Cytochrome b), cox1 (Cytochrome c oxidase subunits 1), cox2 (Cytochrome c
      oxidase subunits 2) and atp6 (ATP synthase subunit 6) and nuclear genes ucp2alpha
      (uncoupling proteins 2 alpha), ucp2beta (uncoupling proteins 2 beta), pparalpha
      (peroxisome proliferator-activated receptor alpha), pparbeta (peroxisome
      proliferatoractivated receptor beta) and ppargc1alpha (proliferator-activated
      receptor gamma coactivator 1 alpha) in fish liver, intestine and muscle, except
      on ppargc1alpha in the muscle which was affected by the diet and the family
      separately. Also, the results revealed that the expression of mitochondrial genes
      is associated with that of nuclear genes involved in electron transport chain in
      fish liver, intestine and muscle. Furthermore, this work showed that the
      expression of mitochondrial genes parallels with the expression of genes encoding
      uncoupling proteins (UCP) in the liver and the intestine of rainbow trout. This
      study for the first time presents the molecular basis of the effects of dietary
      lipid level on mitochondrial and nuclear genes involved in mitochondrial electron
      transport chain in fish. 

PMID- 25853267
TI  - Combined enzymatic and mechanical cell disruption and lipid extraction of green
      alga Neochloris oleoabundans.
AB  - Microalgal biodiesel is one of the most promising renewable fuels. The wet
      technique for lipids extraction has advantages over the dry method, such as
      energy-saving and shorter procedure. The cell disruption is a key factor in wet
      oil extraction to facilitate the intracellular oil release. Ultrasonication, high
      pressure homogenization, enzymatic hydrolysis and the combination of enzymatic
      hydrolysis with high-pressure homogenization and ultrasonication were employed in
      this study to disrupt the cells of the microalga Neochloris oleoabundans. The
      cell disruption degree was investigated. The cell morphology before and after
      disruption was assessed with scanning and transmission electron microscopy. The
      energy requirements and the operation cost for wet cell disruption were also
      estimated. The highest disruption degree, up to 95.41%, assessed by accounting
      method was achieved by the combination of enzymatic hydrolysis and high-pressure
      homogenization. A lipid recovery of 92.6% was also obtained by the combined
      process. The combined process was found to be more efficient and economical
      compared with the individual process. 

PMID- 25853268
TI  - [Position paper to the aut idem substitution obligation on inhalators].

PMID- 25853269
TI  - [Aex - the area under the expiratory flow-volume loop].
AB  - Preschool children often show total expiration times of less than one second in
      pulmonary function tests. Therefore, FEV1 cannot be used for evaluation of
      obstructive pulmonary diseases in small children. Aex, the area under the
      expiratory flow-volume loop, does not depend on the expiration time. The Aex
      value varies according to the convex or concave shape of the flow volume loop,
      can be quantified and is a valuable parameter in the diagnosis of obstructive
      airway diseases.In this study FEV1 und Aex values of 19882 flow-volume loops were
      measured and compared. The comparison shows a very high correlation coefficient
      of r = 0.99.The changes of both parameters in an individual after provocation or
      bronchospasmolysis also demonstrate a strong correlation. A 20 % change of FEV1
      equals an Aex change of 36 %.We conclude that measuring Aex is a good alternative
      to measuring FEV1 especially if the FEV1 cannot be obtained due to short
      expiration times.

PMID- 25853270
TI  - [Angiogenin, bFGF and VEGF: angiogenic markers in breath condensate of patients
      with pulmonary hypertension].
AB  - Pulmonary arterial hypertension (PAH) is associated with a change in vascular
      architecture. A characteristic histological feature is the plexiform lesion.
      Similar alterations are observed in the pulmonary vascular bed of patients with
      chronic thromboembolic pulmonary hypertension (CTEPH). Cytokines involved in
      angiogenesis were found in both serum and lung tissue of patients with PAH and
      CTEPH, although their role in the formation of plexiform lesions remains unclear.
      The examination of breath condensate is a noninvasive technique to analyse
      proteins possibly associated with the pathogenesis of various lung
      diseases.Breath condensate of 22 patients with pulmonary hypertension (PAH: n =
      12; CTEPH: n = 10) and 7 healthy volunteers was examined using a multiplex
      fluorescent bead immunoassay to determine the concentrations of the biomarkers
      angiogenin, bFGF, VEGF, IL-8, and TNF-alpha. Significantly higher levels of
      angiogenin, bFGF and TNF-alpha were observed in breath condensate of patients
      with pulmonary hypertension in comparison to healthy controls. Similarly, breath
      condensate levels of VEGF were elevated in patients with PAH as against healthy
      volunteers. However, IL-8 levels in breath condensate did not differ between the
      two groups. The data suggest that breath condensate of patients with pulmonary
      hypertension is characterized by increased levels of the angiogenic factors
      angiogenin, VEGF and bFGF as well as TNF-alpha, but not IL-8. A larger study is
      needed to confirm these results and to determine the prognostic and therapeutic
      implications of these findings.

PMID- 25853271
TI  - [Availability and integration of palliative medicine at certified lung cancer
      centers].
AB  - BACKGROUND: It is the aim of the certification system for Organ Cancer Centers of
      the German Cancer Society to ensure that oncology patients receive therapy
      meeting high quality standards. Lung cancer patients require comprehensive
      palliative care due to their high symptom load. The purpose of the present study
      was to identify the existing palliative care structures at 39 certified lung
      cancer centers. METHODS: The survey tool used was an 18-question questionnaire
      sent by surface mail to the respective centers. RESULTS: A total of 30 centers
      took part in the survey. A physician with the additional qualification
      'palliative care' was employed at 21 of the centers, a certified palliative care
      nurse worked at 24 centers. A palliative care unit was available at 9 centers.
      The cited obstacles to the delivery of palliative care included a shortage of
      qualified palliative care staff, a lack of refinancing, and the concern that the
      suggestion of palliative care might cause negative emotions in the respective
      patients. CONCLUSIONS: Certified lung cancer centers had a wide range of
      palliative care structures. Openness to and interest in extending existing
      palliative care services were most commonly identified. A number of serious
      obstacles in achieving this goal were nevertheless cited.

PMID- 25853274
TI  - Charge-coupled substituted garnets (Y3-xCa0.5xM0.5x)Fe5O12 (M = Ce, Th):
      structure and stability as crystalline nuclear waste forms.
AB  - The garnet structure has been proposed as a potential crystalline nuclear waste
      form for accommodation of actinide elements, especially uranium (U). In this
      study, yttrium iron garnet (YIG) as a model garnet host was studied for the
      incorporation of U analogs, cerium (Ce) and thorium (Th), incorporated by a
      charge-coupled substitution with calcium (Ca) for yttrium (Y) in YIG, namely,
      2Y(3+) = Ca(2+) + M(4+), where M(4+) = Ce(4+) or Th(4+). Single-phase garnets Y3
      xCa0.5xM0.5xFe5O12 (x = 0.1-0.7) were synthesized by the citrate-nitrate
      combustion method. Ce was confirmed to be tetravalent by X-ray absorption
      spectroscopy and X-ray photoelectron spectroscopy. X-ray diffraction and (57)Fe
      Mossbauer spectroscopy indicated that M(4+) and Ca(2+) cations are restricted to
      the c site, and the local environments of both the tetrahedral and the octahedral
      Fe(3+) are systematically affected by the extent of substitution. The charge
      coupled substitution has advantages in incorporating Ce/Th and in stabilizing the
      substituted phases compared to a single substitution strategy. Enthalpies of
      formation of garnets were obtained by high temperature oxide melt solution
      calorimetry, and the enthalpies of substitution of Ce and Th were determined. The
      thermodynamic analysis demonstrates that the substituted garnets are entropically
      rather than energetically stabilized. This suggests that such garnets may form
      and persist in repositories at high temperature but might decompose near room
      temperature. 

PMID- 25853273
TI  - Scalable synthesis of Fmoc-protected GalNAc-threonine amino acid and T(N) antigen
      via nickel catalysis.
AB  - The highly alpha-selective and scalable synthesis of the Fmoc-protected GalNAc
      threonine amino acid and TN antigen in gram scale (0.5-1 g) is described. The
      challenging 1,2-cis-2-amino glycosidic bond is addressed through a coupling of
      threonine residues with C(2)-N-ortho-(trifluoromethyl)benzylidenamino
      trihaloacetimidate donors mediated by Ni(4-F-PhCN)4(OTf)2. The desired 1,2-cis-2
      amino glycoside was obtained in 66% yield (3.77 g) with alpha-only selectivity
      and subsequently transformed into the Fmoc-protected GalNAc-threonine and TN
      antigen. This operationally simple procedure no longer requires utilization of
      the commonly used C(2)-azido donors and overcomes many of the limitations
      associated with the synthesis of 1,2-cis linkage. 

PMID- 25853275
TI  - Gibbs excess and the calculation of the absolute surface composition of liquid
      binary mixtures.
AB  - Adsorption at the liquid-vapor interphase of a liquid binary mixture is
      traditionally quantified by means of the Gibbs solute excess. Despite several
      theoretical reviews on the meaning of Gibbs excess defined by the Gibbs dividing
      surface, it is still misinterpreted as the excess concentration under
      Guggenheim's finite-depth surface layer approach. In this work, both concepts are
      clarified in a practical way, aided by a graphical representation without loss of
      generality. The understanding of both quantities led to the development of a
      thermodynamic procedure for the calculation of the actual number of solute and
      solvent molecules at a finite-depth surface layer (not a monolayer), what is
      called the absolute surface composition. From surface tension and density data,
      the absolute surface composition of the binary aqueous mixtures of methanol,
      ethanol, 1-propanol, and 1-butanol was calculated. Results show thermodynamic
      consistency and agree with experimental reports and with an empirical mixing
      rule. The increasing alcohol surface concentration throughout the entire
      concentration range casts doubt on the formation of an alcohol monolayer, as was
      suggested by other authors. Furthermore, the use of Guggenheim's monolayer model
      does not reproduce the experimental data, nor does it show thermodynamic
      consistency. 

PMID- 25853276
TI  - Combined Effects of Cadmium and UVB Radiation on Sea Urchin Embryos: Skeleton
      Impairment Parallels p38 MAPK Activation and Stress Genes Overexpression.
AB  - Human and natural activities release many pollutants in the marine environment.
      The mixture of pollutants can affect many organisms concurrently. We used
      Paracentrotus lividus as a model to analyze the effects on signal transduction
      pathways and stress gene expression in embryos exposed continuously to double
      stress, i.e., cadmium (Cd) from fertilization and UVB at cleavage (Cd/UVB
      embryos). By microscopical inspection, we evaluated embryonic morphology after 72
      h of development. Tissue-specific markers were used to assess mesoderm
      differentiation by immunofluorescence. We analyzed p38MAPK, ERK1/2, and JNK
      activation by Western blot and mRNA profiles of Pl-MT, Pl-14-3-3epsilon, and Pl
      jun genes by real-time quantitative polymerase chain reaction (qPCR) and the
      localization of their transcripts by whole mount in situ hybridization (WMISH).
      We found that the Cd/UVB combined exposure induced morphological malformations in
      76% of pluteus embryos, mainly affecting the development of the skeleton,
      including the normal branching of skeletal roads. In Cd/UVB-embryos, p38MAPK was
      activated 1 h after UVB exposure and a remarkable overexpression of the Pl-MT, Pl
      14.3.3epsilon, and Pl-jun genes 24 h after UVB exposure. Pl-MT and Pl
      14.3.3epsilon mRNAs were misexpressed as they were localized in a position
      different from that observed in wild-type embryos, i.e., the intestine. On the
      contrary, Pl-jun mRNA has remained localized in the skeletogenic cells despite
      their displacement in exposed embryos. In conclusion, Cd/UVB exposure affected
      skeletal patterning producing alternative morphologies in which p38MAPK
      activation and Pl-MT, Pl-14.3.3epsilon, and Pl-jun gene overexpression seem
      linked to a protective role against the stress response induced by Cd/UVB. 

PMID- 25853277
TI  - Improvement in PbS-based Hybrid Bulk-Heterojunction Solar Cells through Band
      Alignment via Bismuth Doping in the Nanocrystals.
AB  - We introduce dopants in lead sulfide (PbS) quantum dots (QDs) in forming hybrid
      bulk-heterojunction (BHJ) solar cells. Because an increase in the content of
      bismuth as dopants in PbS QDs transforms the intrinsic p-type semiconductor into
      an n-type one, the band alignment between a conjugated polymer and the doped QDs
      changes upon doping affecting performance of BHJ solar cells. From scanning
      tunneling spectroscopy (STS) of the doped QDs, we observe a shift in their Fermi
      energy leading to formation of a type II band alignment in the polymer:doped-QD
      interface. We also show that the dopants improve electron-conduction process
      through the QDs. With the dopants controlling both band alignments at the
      interface and the conduction process, we show that the dopant concentration in
      QDs influences open-circuit voltage unfavorably and short-circuit current in a
      beneficial manner. The device performance of hybrid BHJ solar cells is hence
      maximized at an optimum concentration of bismuth in PbS QDs. 

PMID- 25853278
TI  - Thermal activation of superheated lipid-coated perfluorocarbon drops.
AB  - This study explored the thermal conditions necessary for the vaporization of
      superheated perfluorocarbon nanodrops. Droplets C3F8 and C4F10 coated with a
      homologous series of saturated diacylphosphatidylcholines were formed by
      condensation of 4 MUm diameter microbubbles. These drops were stable at room
      temperature and atmospheric pressure, but they vaporized back into microbubbles
      at higher temperatures. The vaporization transition was measured as a function of
      temperature by laser light extinction. We found that C3F8 and C4F10 drops
      experienced 90% vaporization at 40 and 75  degrees C, respectively, near the
      theoretical superheat limits (80-90% of the critical temperature). We therefore
      conclude that the metastabilty of these phase-change agents arises not from the
      droplet Laplace pressure altering the boiling point, as previously reported, but
      from the metastability of the pure superheated fluid to homogeneous nucleation.
      The rate of C4F10 drop vaporization was quantified at temperatures ranging from
      55 to 75  degrees C, and an apparent activation energy barrier was calculated
      from an Arrhenius plot. Interestingly, the activation energy increased linearly
      with acyl chain length from C14 to C20, indicating that lipid interchain cohesion
      plays an important role in suppressing the vaporization rate. The vaporized drops
      (microbubbles) were found to be unstable to dissolution at high temperatures,
      particularly for C14 and C16. However, proper choice of the fluorocarbon and
      lipid species provided a nanoemulsion that could undergo at least ten reversible
      condensation/vaporization cycles. The vaporization properties presented in this
      study may facilitate the engineering of tunable phase-shift particles for
      diagnostic imaging, targeted drug delivery, tissue ablation, and other
      applications. 

PMID- 25853279
TI  - Superelastic and superhydrophobic nanofiber-assembled cellular aerogels for
      effective separation of oil/water emulsions.
AB  - Many applications proposed for functional nanofibers require their assembly into
      a monolithic cellular structure. The ability to maintain structural integrity
      upon large deformation is essential to ensure a macroscopic cellular material
      that functions reliably. However, it remains a great challenge to achieve high
      elasticity in three-dimensional (3D) nanofibrous networks. Here, we report a
      strategy to create fibrous, isotropically bonded elastic reconstructed (FIBER)
      aerogels with a hierarchical cellular structure and superelasticity by combining
      electrospun nanofibers and the freeze-shaping technique. Our approach allows the
      intrinsically lamellar deposited electrospun nanofibers to assemble into elastic
      bulk aerogels with tunable porous structure and wettability on a large scale. The
      resulting FIBER aerogels exhibit the integrated properties of ultralow density
      (<30 mg cm(-3)), rapid recovery from 80% compression strain, superhydrophobic
      superoleophilic wettability, and high pore tortuosity. More interestingly, the
      FIBER aerogels can effectively separate surfactant-stabilized water-in-oil
      emulsions, solely using gravity, with high flux (maximum of 8140 +/- 220 L m(-2)
      h(-1)) and high separation efficiency, which match well with the requirements for
      treating the real emulsions. The synthesis of FIBER aerogels also provides a
      versatile platform for exploring the applications of nanofibers in a self
      supporting, structurally adaptive, and 3D macroscopic form. 

PMID- 25853280
TI  - (68)Ga-labeled 3PRGD2 for dual PET and Cerenkov luminescence imaging of
      orthotopic human glioblastoma.
AB  - beta-Emitters can produce Cerenkov radiation that is detectable by Cerenkov
      luminescence imaging (CLI), allowing the combination of PET and CLI with one
      radiotracer for both tumor diagnosis and visual guidance during surgery.
      Recently, the clinical feasibility of CLI with the established therapeutic
      reagent Na(131)I and the PET tracer (18)F-FDG was demonstrated. (68)Ga possesses
      a higher Cerenkov light output than (18)F and (131)I, which would result in
      higher sensitivity for CLI and improve the outcome of CLI in clinical
      applications. However, the research on (68)Ga-based tumor-specific tracers for
      CLI is limited. In this study, we examined the use of (68)Ga-radiolabeled DOTA
      3PRGD2 ((68)Ga-3PRGD2) for dual PET and CLI of orthotopic U87MG human
      glioblastoma. For this purpose, the Cerenkov efficiencies of (68)Ga and (18)F
      were measured with the IVIS Spectrum system (PerkinElmer, USA). The CLI signal
      intensity of (68)Ga was 15 times stronger than that of (18)F. PET and CLI of
      (68)Ga-3PRGD2 were performed in U87MG human glioblastoma xenografts. Both PET and
      CLI revealed a remarkable accumulation of (68)Ga-3PRGD2 in the U87MG human
      glioblastoma xenografts at 1 h p.i. with an extremely low background in the brain
      when compared with (18)F-FDG. Furthermore, (68)Ga-3PRGD2 was used for dual PET
      and CLI of orthotopic human glioblastoma. The orthotopic human glioblastoma was
      clearly visualized by both imaging modalities. In addition, the biodistribution
      of (68)Ga-3PRGD2 was assessed in normal mice to estimate the radiation dosimetry.
      The whole-body effective dose is 20.1 +/- 3.3 MUSv/MBq, which is equal to 3.7 mSv
      per whole-body PET scan with a 5 mCi injection dose. Thus, (68)Ga-3PRGD2 involves
      less radiation exposure in patients when compared with (18)F-FDG (7.0 mSv). The
      use of (68)Ga-3PRGD2 in dual PET and CLI shows great promise for tumor diagnosis
      and image-guided surgery. 

PMID- 25853282
TI  - New bioinformatic tool for quick identification of functionally relevant
      endogenous retroviral inserts in human genome.
AB  - Endogenous retroviruses (ERVs) and LTR retrotransposons (LRs) occupy ~8% of human
      genome. Deep sequencing technologies provide clues to understanding of functional
      relevance of individual ERVs/LRs by enabling direct identification of
      transcription factor binding sites (TFBS) and other landmarks of functional
      genomic elements. Here, we performed the genome-wide identification of human
      ERVs/LRs containing TFBS according to the ENCODE project. We created the first
      interactive ERV/LRs database that groups the individual inserts according to
      their familial nomenclature, number of mapped TFBS and divergence from their
      consensus sequence. Information on any particular element can be easily extracted
      by the user. We also created a genome browser tool, which enables quick mapping
      of any ERV/LR insert according to genomic coordinates, known human genes and
      TFBS. These tools can be used to easily explore functionally relevant individual
      ERV/LRs, and for studying their impact on the regulation of human genes. Overall,
      we identified ~110,000 ERV/LR genomic elements having TFBS. We propose a
      hypothesis of "domestication" of ERV/LR TFBS by the genome milieu including
      subsequent stages of initial epigenetic repression, partial functional release,
      and further mutation-driven reshaping of TFBS in tight coevolution with the
      enclosing genomic loci. 

PMID- 25853283
TI  - Voxel-wise meta-analyses of brain blood flow and local synchrony abnormalities in
      medication-free patients with major depressive disorder.
AB  - BACKGROUND: Published meta-analyses of resting-state regional cerebral blood flow
      (rCBF) studies of major depressive disorder (MDD) have included patients
      receiving antidepressants, which might affect brain activity and thus bias the
      results. To our knowledge, no meta-analysis has investigated regional homogeneity
      changes in medication-free patients with MDD. Moreover, an association between
      regional homogeneity and rCBF has been demonstrated in some brain regions in
      healthy controls. We sought to explore to what extent resting-state rCBF and
      regional homogeneity changes co-occur in the depressed brain without the
      potential confound of medication. METHODS: Using the effect-size signed
      differential mapping method, we conducted 2 meta-analyses of rCBF and regional
      homogeneity studies of medication-free patients with MDD. RESULTS: Our systematic
      search identified 14 rCBF studies and 9 regional homogeneity studies. We
      identified conjoint decreases in resting-state rCBF and regional homogeneity in
      the insula and superior temporal gyrus in medication-free patients with MDD
      compared with controls. Other changes included altered resting-state rCBF in the
      precuneus and in the frontal-limbic-thalamic-striatal neural circuit as well as
      altered regional homogeneity in the uncus and parahippocampal gyrus. Meta
      regression revealed that the percentage of female patients with MDD was
      negatively associated with resting-state rCBF in the right anterior cingulate
      cortex and that the age of patients with MDD was negatively associated with rCBF
      in the left insula and with regional homogeneity in the left uncus. LIMITATIONS:
      The analysis techniques, patient characteristics and clinical variables of the
      included studies were heterogeneous. CONCLUSION: The conjoint alterations of rCBF
      and regional homogeneity in the insula and superior temporal gyrus may be core
      neuropathological changes in medication-free patients with MDD and serve as a
      specific region of interest for further studies on MDD.

PMID- 25853286
TI  - Assessing infertility-related stress: the factor structure of the Fertility
      Problem Inventory in Italian couples undergoing infertility treatment.
AB  - The factor structure of the Fertility Problem Inventory (FPI) and its invariance
      across gender were examined in Italian couples undergoing infertility treatment.
      About 1000 subjects (both partners of 500 couples) completed two questionnaires
      prior to commencing infertility treatment at a private Clinic in Palermo, Italy.
      Confirmatory Factor Analysis demonstrated that the original factor structure of
      the FPI was partially confirmed. Two correlated factors (Infertility Life Domains
      and Importance of Parenthood) were obtained via a post hoc Exploratory Factor
      Analysis. Finally, the invariance of this factor structure across gender was
      confirmed. The study supported the relevance of two interrelated factors specific
      to infertility stress which could help clinicians to focus on the core
      infertility-related stress domains of infertile couples. 

PMID- 25853285
TI  - Microstructural abnormalities of the brain white matter in attention
      deficit/hyperactivity disorder.
AB  - BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is an early-onset
      neurodevelopmental disorder with multiple behavioural problems and executive
      dysfunctions for which neuroimaging studies have reported a variety of
      abnormalities, with inconsistencies partly owing to confounding by medication and
      concurrent psychiatric disease. We aimed to investigate the microstructural
      abnormalities of white matter in unmedicated children and adolescents with pure
      ADHD and to explore the association between these abnormalities and behavioural
      symptoms and executive functions. METHODS: We assessed children and adolescents
      with ADHD and healthy controls using psychiatric interviews. Behavioural problems
      were rated using the revised Conners' Parent Rating Scale, and executive
      functions were measured using the Stroop Colour-Word Test and the Wisconsin Card
      Sorting test. We acquired diffusion tensor imaging data using a 3 T MRI system,
      and we compared diffusion parameters, including fractional anisotropy (FA) and
      mean, axial and radial diffusivities, between the 2 groups. RESULTS: Thirty-three
      children and adolescents with ADHD and 35 healthy controls were included in our
      study. In patients compared with controls, FA was increased in the left posterior
      cingulum bundle as a result of both increased axial diffusivity and decreased
      radial diffusivity. In addition, the averaged FA of the cluster in this region
      correlated with behavioural measures as well as executive function in patients
      with ADHD. LIMITATIONS: This study was limited by its cross-sectional design and
      small sample size. The cluster size of the significant result was small.
      CONCLUSION: Our findings suggest that white matter abnormalities within the
      limbic network could be part of the neural underpinning of behavioural problems
      and executive dysfunction in patients with ADHD.

PMID- 25853284
TI  - Using structural MRI to identify individuals at genetic risk for bipolar
      disorders: a 2-cohort, machine learning study.
AB  - BACKGROUND: Brain imaging is of limited diagnostic use in psychiatry owing to
      clinical heterogeneity and low sensitivity/specificity of between-group
      neuroimaging differences. Machine learning (ML) may better translate neuroimaging
      to the level of individual participants. Studying unaffected offspring of parents
      with bipolar disorders (BD) decreases clinical heterogeneity and thus increases
      sensitivity for detection of biomarkers. The present study used ML to identify
      individuals at genetic high risk (HR) for BD based on brain structure. METHODS:
      We studied unaffected and affected relatives of BD probands recruited from 2
      sites (Halifax, Canada, and Prague, Czech Republic). Each participant was
      individually matched by age and sex to controls without personal or family
      history of psychiatric disorders. We applied support vector machines (SVM) and
      Gaussian process classifiers (GPC) to structural MRI. RESULTS: We included 45
      unaffected and 36 affected relatives of BD probands matched by age and sex on an
      individual basis to healthy controls. The SVM of white matter distinguished
      unaffected HR from control participants (accuracy = 68.9%, p = 0.001), with
      similar accuracy for the GPC (65.6%, p = 0.002) or when analyzing data from each
      site separately. Differentiation of the more clinically heterogeneous affected
      familiar group from healthy controls was less accurate (accuracy = 59.7%, p =
      0.05). Machine learning applied to grey matter did not distinguish either the
      unaffected HR or affected familial groups from controls. The regions that most
      contributed to between-group discrimination included white matter of the
      inferior/middle frontal gyrus, inferior/middle temporal gyrus and precuneus.
      LIMITATIONS: Although we recruited 126 participants, ML benefits from even larger
      samples. CONCLUSION: Machine learning applied to white but not grey matter
      distinguished unaffected participants at high and low genetic risk for BD based
      on regions previously implicated in the pathophysiology of BD.

PMID- 25853288
TI  - The Influence of Interfaces on Properties of Thin-Film Inorganic Structural
      Isomers Containing SnSe-NbSe2 Subunits.
AB  - Inorganic isomers
      ([SnSe]1+delta)m(NbSe2)n([SnSe]1+delta)p(NbSe2)q([SnSe]1+delta)r(NbSe2)s where m,
      n, p, q, r, and s are integers and m + p + r = n + q + s = 4 were prepared using
      the modulated elemental reactant technique. This series of all six possible
      isomers provides an opportunity to study the influence of interface density on
      properties while maintaining the same unit cell size and composition. As
      expected, all six compounds were observed to have the same atomic compositions
      and an almost constant c-axis lattice parameter of ~4.90(5) nm, with a slight
      trend in the c-axis lattice parameter correlated with the different number of
      interfaces in the isomers: two, four and six. The structures of the constituents
      in the ab-plane were independent of one another, confirming the nonepitaxial
      relationship between them. The temperature dependent electrical resistivities
      revealed metallic behavior for all the six compounds. Surprisingly, the
      electrical resistivity at room temperature decreases with increasing number of
      interfaces. Hall measurements suggest this results from changes in carrier
      concentration, which increases with increasing thickness of the thickest SnSe
      block in the isomer. Carrier mobility scales with the thickness of the thickest
      NbSe2 block due to increased interfacial scattering as the NbSe2 blocks become
      thinner. The observed behavior suggests that the two constituents serve different
      purposes with respect to electrical transport. SnSe acts as a charge donor and
      NbSe2 acts as the charge transport layer. This separation of function suggests
      that such heterostructures can be designed to optimize performance through choice
      of constituent, layer thickness, and layer sequence. A simplistic model, which
      predicts the properties of the complex isomers from a weighted sum of the
      properties of building blocks, was developed. A theoretical model is needed to
      predict the optimal compound for specific properties among the many potential
      compounds that can be prepared. 

PMID- 25853287
TI  - Antioxidant capacity and phenolic composition of leaves from 10 Bene (Pistacia
      atlantica subsp. kurdica) genotypes.
AB  - Leaves of 10 Bene genotypes were collected from six provinces (West Azerbaijan,
      Kurdistan, Kermanshah, Ilam, Hamedan and Lorestan) in Iran. This study was
      carried out to better characterise the total phenolic and flavonoid contents,
      antioxidant capacity and phenolic composition, as well as to evaluate the
      correlation between content of phenolic compounds and antioxidant activity in 10
      genotypes of Bene. The antioxidant activity of leaf extracts was measured using
      different assays: ferric reducing antioxidant power, nitric oxide radical
      scavenging and 2,2-diphenyl-1-picrylhydrazyl. The results indicated that the
      antioxidant capacity can be related to total phenolic and flavonoid content, so
      that among all the genotypes studied here, the highest and the lowest phenolic
      content and antioxidant activity were observed in B2 and B10 genotypes,
      respectively. Analysing the phenolic composition using high performance liquid
      chromatography, caffeic acid, vanillic acid, ferulic acid and sinapic acid were
      found in all investigated genotypes. 

PMID- 25853289
TI  - Optical diagnosis of the progression and reversal of CCl4-induced liver injury in
      rodent model using minimally invasive autofluorescence spectroscopy.
AB  - Worldwide, liver cancer is the fifth most common cancer in men and seventh most
      common cancer in women. Intoxicant-induced liver injury is one of the major
      causes for severe structural damage with fibrosis and functional derangement of
      the liver leading to cancer in its later stages. This report focuses on the
      minimally invasive autofluorescence spectroscopic (AFS) studies on intoxicant,
      carbon tetrachloride (CCl4)-induced liver damage in a rodent model. Different
      stages of liver damage, including the reversed stage, on stoppage of the
      intoxicant are examined. Emission from prominent fluorophores, such as collagen,
      nicotinamide adenine dinucleotide (NADH), and flavin adenine dinucleotide (FAD),
      and variations in redox ratio have been studied. A direct correlation between the
      severity of the disease and the levels of collagen and redox ratio was observed.
      On withdrawal of the intoxicant, a gradual reversal of the disease to normal
      conditions was observed as indicated by the decrease in collagen levels and redox
      ratio. Multivariate statistical techniques and principal component analysis
      followed by linear discriminant analysis (PC-LDA) were used to develop diagnostic
      algorithms for distinguishing different stages of the liver disease based on
      spectral features. The PC-LDA modeling on a minimally invasive AFS dataset
      yielded diagnostic sensitivities of 93%, 87% and 87% and specificities of 90%,
      98% and 98% for pairwise classification among normal, fibrosis, cirrhosis and
      reversal conditions. We conclude that AFS along with PC-LDA algorithm has the
      potential for rapid and accurate minimally invasive diagnosis and detection of
      structural changes due to liver injury resulting from various intoxicants. 

PMID- 25853290
TI  - Survival of Microencapsulated Probiotic Bacteria after Processing and during
      Storage: A Review.
AB  - The use of live probiotic bacteria as food supplement has become popular.
      Capability of probiotic bacteria to be kept at room temperature becomes necessary
      for customer's convenience and manufacturer's cost reduction. Hence, production
      of dried form of probiotic bacteria is important. Two common drying methods
      commonly used for microencapsulation are freeze drying and spray drying. In spite
      of their benefits, both methods have adverse effects on cell membrane integrity
      and protein structures resulting in decrease in bacterial viability.
      Microencapsulation of probiotic bacteria has been a promising technology to
      ensure bacterial stability during the drying process and to preserve their
      viability during storage without significantly losing their functional properties
      such acid tolerance, bile tolerance, surface hydrophobicity, and enzyme
      activities. Storage at room temperatures instead of freezing or low temperature
      storage is preferable for minimizing costs of handling, transportation, and
      storage. Concepts of water activity and glass transition become important in
      terms of determination of bacterial survival during the storage. The
      effectiveness of microencapsulation is also affected by microcapsule materials.
      Carbohydrate- and protein-based microencapsulants and their combination are
      discussed in terms of their protecting effect on probiotic bacteria during
      dehydration, during exposure to harsh gastrointestinal transit and small
      intestine transit and during storage. 

PMID- 25853291
TI  - The effects of the frequency of the initial treatment with intravitreal
      bevacizumab on macular volume and visual acuity.
AB  - PURPOSE: The ideal notion of monthly intravitreal injections is difficult to
      achieve when it comes to real-life scenarios. In reality, patients often are
      treated with larger intervals due to circumstances. The purpose of this study was
      to compare the results of intravitreal bevacizumab injections with shorter
      intervals versus longer intervals for the treatment of choroidal
      neovascularization (CNV) in age-related macular degeneration (AMD) in a real-life
      clinic. METHODS: A retrospective, consecutive cohort study of naive eyes of
      patients with CNV secondary to AMD treated with intravitreal bevacizumab.
      Patients included underwent at least 3 consecutive injections with intervals <45
      days in between them (Group A) or >45 days (Group B). Best corrected visual
      acuity (BCVA) and optical coherence tomography were performed before the initial
      intravitreal injections and after the last injection. RESULTS: Group A consisted
      of 24 eyes of 18 patients and Group B 30 eyes of 25 patients. There was a
      significantly larger mean of consecutive (5.0 vs. 3.78, P = 0.013) and total
      (9.44 vs. 7.2, P = 0.021) injections in Group B. There was a significant
      improvement in average BCVA in Group A only (0.65-0.52, P=0.006). However, a
      significant and similar improvement in retinal volume was found in both groups (P
      < 0.05). CONCLUSION: This study emphasizes the importance of achieving
      consecutive injections with short intervals. Practitioners and decision makers
      should be mindful that providing additional resources to accomplish proper
      frequency may be more effective (visual outcome), cost effective (less
      injections), and safer (less exposure) for the patient.

PMID- 25853292
TI  - Classification of solid dispersions: correlation to (i) stability and solubility
      (ii) preparation and characterization techniques.
AB  - Solid dispersion has been a topic of interest in recent years for its potential
      in improving oral bioavailability, especially for poorly water soluble drugs
      where dissolution could be the rate-limiting step of oral absorption.
      Understanding the physical state of the drug and polymers in solid dispersions is
      essential as it influences both the stability and solubility of these systems.
      This review emphasizes on the classification of solid dispersions based on the
      physical states of drug and polymer. Based on this classification, stability
      aspects such as crystallization tendency, glass transition temperature (Tg), drug
      polymer miscibility, molecular mobility, etc. and solubility aspects have been
      discussed. In addition, preparation and characterization methods for binary solid
      dispersions based on the classification have also been discussed. 

PMID- 25853293
TI  - A dimensionless variable for the scale up and transfer of a roller compaction
      formulation.
AB  - Roller compaction is the most commonly employed dry granulation process in the
      pharmaceutical industry. While this process is increasingly used as an
      alternative to wet granulation, there are no parameter sets or system of
      equations to quickly scale up or transfer a formulation between two pieces of
      equipment. In this work, dimensionless variable was examined as a method to
      transfer the operating parameters of a formulation between two different pieces
      of equipment. This work was completed to establish the ground work for the
      development of a dimensionless relationship relating the operating parameters of
      the equipment to the porosity of the ribbon. The working hypothesis was three
      fold, namely (i) that ribbons of the same porosity made with different equipment
      will have similar properties, (ii) that it is possible to establish an objective
      relationship between ribbon porosity and a combination of operating parameters
      and raw material attributes and (iii) that by expressing such parameter
      combination as a dimensionless variable, it will be possible to use the same
      relationship for different pieces of roller compaction equipment. The
      dimensionless variable RP/RS*HFS*True Density*D2 was found to correlate well with
      the ribbon porosity for the formulations and equipment used in these experiments.
      Depending on the formulation, the average difference in ribbon porosity between
      the two units varied between 0.012 and 0.024.

PMID- 25853294
TI  - Construction and in vitro/in vivo evaluation of 17-allylamino-17
      demethoxygeldanamycin (17AAG)-loaded PEGylated nanostructured lipid carriers.
AB  - In this study, the PEGylated nanostructured lipid carriers (PEG-NLC) were
      constructed for the intravenous delivery of 17-allylamino-17
      demethoxygeldanamycin (17AAG). 17AAG-PEG-NLC was successfully prepared by the
      method of emulsion evaporation at a high temperature and solidification at a low
      temperature using a mixture of glycerol monostearate and PEG2000-stearate as
      solid lipids, and medium-chain triglyceride as the liquid lipid. The results
      revealed that the morphology of the NLC was spheroidal. The particle size, zeta
      potential and entrapment efficiency for 17AAG-PEG-NLC were observed as 189.4 nm, 
      20.2 mV and 83.42%, respectively. X-ray diffraction analysis revealed that 17AAG
      existed as amorphous structures in the nanoparticles. In the in vitro release
      study, the 17AAG from 17AAG-PEG-NLC exhibited a biphasic release pattern with
      burst release initially and sustained release afterwards. In addition, 17AAG-PEG
      NLC showed a significantly higher in vitro antitumor efficacy and longer
      retention time in vivo than 17AAG solution. These results indicated that 17AAG
      PEG-NLC may offer a promising alternative to the current 17AAG formulations for
      the treatment of solid tumors.

PMID- 25853297
TI  - Influence of emulsification process on the properties of Pickering emulsions
      stabilized by layered double hydroxide particles.
AB  - This paper reports the influence of emulsification process on the packing of
      layered double hydroxide (LDH) particles at the aqueous/oil phase interface and
      the properties of the resulting Pickering emulsions. Emulsions prepared by
      ultrasonication display superior long-term stability and gel-like characteristics
      at the dispersed phase volume fraction well below the random close packing limit,
      whereas emulsions with same compositions prepared by vortex mixing show some
      extent of sedimentation and liquid-like behaviors. Rheological measurements
      demonstrate that the zero-shear elastic modulus and yield stress of gel-like
      emulsions exhibit power-law dependences on particle concentration and
      independence on aqueous/oil phase ratio. The microstructural origin of this
      behavior is investigated by optical microscopy, revealing the droplets become
      strongly adhesive and a heterogeneous percolating network is formed among
      neighboring droplets. Fluorescent confocal microscopy measurements further
      confirm that the droplet adhesion is due to particle layers bridging opposite
      interfaces. In contrast, homogeneous, isolated, and densely packed droplets are
      present in emulsions prepared by vortex mixing, which results in these systems
      being dominantly viscous like the suspending fluid. This study shows that the
      emulsification process can be used as a trigger to modify long-term stability and
      rheology of solid-stabilized multiphase mixtures, which greatly expands their
      potential technological applications. 

PMID- 25853295
TI  - Unraveling heterogeneous susceptibility and the evolution of breast cancer using
      a systems biology approach.
AB  - BACKGROUND: An essential question in cancer is why individuals with the same
      disease have different clinical outcomes. Progress toward a more personalized
      medicine in cancer patients requires taking into account the underlying
      heterogeneity at different molecular levels. RESULTS: Here, we present a model in
      which there are complex interactions at different cellular and systemic levels
      that account for the heterogeneity of susceptibility to and evolution of ERBB2
      positive breast cancers. Our model is based on our analyses of a cohort of mice
      that are characterized by heterogeneous susceptibility to ERBB2-positive breast
      cancers. Our analysis reveals that there are similarities between ERBB2 tumors in
      humans and those of backcross mice at clinical, genomic, expression, and
      signaling levels. We also show that mice that have tumors with intrinsically high
      levels of active AKT and ERK are more resistant to tumor metastasis. Our findings
      suggest for the first time that a site-specific phosphorylation at the serine 473
      residue of AKT1 modifies the capacity for tumors to disseminate. Finally, we
      present two predictive models that can explain the heterogeneous behavior of the
      disease in the mouse population when we consider simultaneously certain genetic
      markers, liver cell signaling and serum biomarkers that are identified before the
      onset of the disease. CONCLUSIONS: Considering simultaneously tumor
      pathophenotypes and several molecular levels, we show the heterogeneous behavior
      of ERBB2-positive breast cancer in terms of disease progression. This and similar
      studies should help to better understand disease variability in patient
      populations.

PMID- 25853296
TI  - PGC-1alpha activity in nigral dopamine neurons determines vulnerability to alpha
      synuclein.
AB  - INTRODUCTION: Mitochondrial dysfunction and oxidative stress are critical factors
      in the pathogenesis of age-dependent neurodegenerative diseases. PGC-1alpha, a
      master regulator of mitochondrial biogenesis and cellular antioxidant defense,
      has emerged as a possible therapeutic target for Parkinson's disease, with
      important roles in the function and survival of dopaminergic neurons in the
      substantia nigra. The objective of this study is to determine if the loss of PGC
      1alpha activity contributes to alpha-synuclein-induced degeneration. RESULTS: We
      explore the vulnerability of PGC-1alpha null mice to the accumulation of human
      alpha-synuclein in nigral neurons, and assess the neuroprotective effect of AAV
      mediated PGC-1alpha expression in this experimental model. Using neuronal
      cultures derived from these mice, mitochondrial respiration and production of
      reactive oxygen species are assessed in conditions of human alpha-synuclein
      overexpression. We find ultrastructural evidence for abnormal mitochondria and
      fragmented endoplasmic reticulum in the nigral dopaminergic neurons of PGC-1alpha
      null mice. Furthermore, PGC-1alpha null nigral neurons are more prone to
      degenerate following overexpression of human alpha-synuclein, an effect more
      apparent in male mice. PGC-1alpha overexpression restores mitochondrial
      morphology, oxidative stress detoxification and basal respiration, which is
      consistent with the observed neuroprotection against alpha-synuclein toxicity in
      male PGC-1alpha null mice. CONCLUSIONS: Altogether, our results highlight an
      important role for PGC-1alpha in controlling the mitochondrial function of nigral
      neurons accumulating alpha-synuclein, which may be critical for gender-dependent
      vulnerability to Parkinson's disease.

PMID- 25853298
TI  - Aqueous Eu(II)-Containing Complex with Bright Yellow Luminescence.
AB  - Eu(II)-containing materials have unique luminescence, redox, and magnetic
      properties that have potential applications in optoelectronics, sensors, and
      imaging. Here, we report the synthesis and characterization of Eu(II)-containing
      aza-222 cryptate that displays yellow luminescence and a quantum yield of 26% in
      aqueous media. The crystal structure reveals a staggered hula-hoop geometry. Both
      solid-state and solution-phase data are presented that indicate that the high
      quantum yield is a result of the absence of OH oscillators in the inner sphere of
      the complex. We expect that Eu(II)-containing aza-222 cryptate is a step toward
      Eu(II)-containing luminescent materials that can be used in a variety of
      applications including biological imaging. 

PMID- 25853299
TI  - A de novo FOXP1 variant in a patient with autism, intellectual disability and
      severe speech and language impairment.
AB  - FOXP1 (forkhead box protein P1) is a transcription factor involved in the
      development of several tissues, including the brain. An emerging phenotype of
      patients with protein-disrupting FOXP1 variants includes global developmental
      delay, intellectual disability and mild to severe speech/language deficits. We
      report on a female child with a history of severe hypotonia, autism spectrum
      disorder and mild intellectual disability with severe speech/language impairment.
      Clinical exome sequencing identified a heterozygous de novo FOXP1 variant
      c.1267_1268delGT (p.V423Hfs*37). Functional analyses using cellular models show
      that the variant disrupts multiple aspects of FOXP1 activity, including
      subcellular localization and transcriptional repression properties. Our findings
      highlight the importance of performing functional characterization to help
      uncover the biological significance of variants identified by genomics
      approaches, thereby providing insight into pathways underlying complex
      neurodevelopmental disorders. Moreover, our data support the hypothesis that de
      novo variants represent significant causal factors in severe sporadic disorders
      and extend the phenotype seen in individuals with FOXP1 haploinsufficiency. 

PMID- 25853301
TI  - Albumin: the next-generation delivery technology.

PMID- 25853302
TI  - 'Close-to-ideal' tumor boron targeting for boron neutron capture therapy is
      possible with 'less-than-ideal' boron carriers approved for use in humans.

PMID- 25853303
TI  - The potential use of trigeminal nerve stimulation in the treatment of epilepsy.

PMID- 25853300
TI  - PIAS4 is associated with macro/microcephaly in the novel interstitial 19p13.3
      microdeletion/microduplication syndrome.
AB  - Array comparative genomic hybridization (aCGH) is a powerful genetic tool that
      has enabled the identification of novel imbalances in individuals with
      intellectual disability (ID), autistic disorders and congenital malformations.
      Here we report a 'genotype first' approach using aCGH on 13 unrelated patients
      with 19p13.3 submicroscopic rearrangement (11 deletions and 2 duplications) and
      review cases in the literature and in public databases. Shared phenotypic
      features suggest that these patients represent an interstitial
      microdeletion/microduplication syndrome at 19p13.3. Common features consist of
      abnormal head circumference in most patients (macrocephaly with the deletions and
      microcephaly with the duplications), ID with developmental delay (DD), hypotonia,
      speech delay and common dysmorphic features. The phenotype is associated with at
      least a ~0.113 Mb critical region harboring three strong candidate genes probably
      associated with DD, ID, speech delay and other dysmorphic features: MAP2K2,
      ZBTB7A and PIAS4, an E3 ubiquitin ligase involved in the ubiquitin signaling
      pathways, which we hypothesize for the first time to be associated with head size
      in humans. 

PMID- 25853305
TI  - Subcutaneous formulation of tocilizumab for treatment of rheumatoid arthritis.
AB  - Tocilizumab (TCZ) is a humanized monoclonal antibody against the IL-6 receptor
      that is indicated for the treatment of rheumatoid arthritis (RA), juvenile
      idiopathic arthritis and Castleman's disease. TCZ was developed as an intravenous
      (IV) formulation and approved for RA treatment in Japan (2008), the EU (2009) and
      the USA (2010). Recently, a subcutaneous (SC) formulation of TCZ was developed
      and approved for RA treatment. Efficacy and safety of TCZ-SC were reported
      through three randomized trials: MUSASHI, SUMMACTA and BREVACTA. Clinical
      efficacy and overall safety of TCZ-SC was comparable to that of TCZ-IV. However
      TCZ-SC, which is provided in a fixed dose, the efficacy was affected by patient
      weight. The frequencies of injection site reactions and anti-TCZ antibodies were
      increased with TCZ-SC compared with TCZ-IV, although differences were minimal and
      at a negligible level for daily clinical practice. This review highlights the
      potential of TCZ-SC in RA treatment. 

PMID- 25853306
TI  - Pulmonary delivery of anorectic oxyntomodulin in rats: food intake suppression,
      reduced body weight gain and pharmacokinetics.
AB  - BACKGROUND: Oxyntomodulin (OXM1-37) is an anorectic gut-secreting peptide with a
      promise to treat obesity, but its needle-free delivery has yet to be successful.
      RESULTS: Pulmonary delivery of OXM1-37, but not its C-terminal octapeptides,
      caused dose-related, transient 4-6 h food intake suppression in rats. At 0.5
      mg/kg, its 30-38% food intake suppression led to 46% reduction in body weight
      gain by day 8. Its lung absorption was fast, elevating the systemic level
      rapidly, yet the bioavailability was low at 13%. In the brain, twofold neuronal c
      fos activation was seen in the hypothalamus arcuate nucleus and brainstem area
      postrema. CONCLUSION: Pulmonary delivery is a promising needle-free systemic
      delivery option for OXM1-37 to treat obesity, as enabling effective lung
      absorption and brain interaction.

PMID- 25853307
TI  - Gold nanoparticle-enhanced photodynamic therapy: effects of surface charge and
      mitochondrial targeting.
AB  - AIM: The authors aimed to further improve the efficiency and selectivity of gold
      nanoparticle (Au NP)-assisted photodynamic therapy by modulating the surface
      charge of Au NPs and delivering Au NPs particularly to mitochondria of breast
      cancer cells. METHODS: Solid gold nanospheres (~50 nm) with negative and positive
      surface charge were synthesized respectively, and mitochondria-targeting Au NPs
      were prepared by conjugating with triphenylphosphonium molecules. CONCLUSION:
      Positively charged Au NPs were preferably taken up by breast cancer cells.
      Combination of positive surface charge with mitochondria-targeting domain onto Au
      NPs allowed their accumulation in the mitochondria of breast cancer cells to
      significantly elevate reactive oxygen species formation in 5-aminolevulinic-acid
      enabled photodynamic therapy and improve selective destruction of breast cancer
      cells.

PMID- 25853308
TI  - miRNA therapy targeting cancer stem cells: a new paradigm for cancer treatment
      and prevention of tumor recurrence.
AB  - Cancer stem cells (CSCs) are a small subpopulation of cells within tumors that
      retain the properties of self-renewal and tumorigenicity in vivo. Although CSCs
      have been reported in multiple cancers, the regulation of CSCs has not been
      described at the molecular level. miRNAs are endogenous small noncoding RNAs that
      post-transcriptionally regulate the expression of their target genes via RNA
      interference and are involved in almost all cellular processes. Since aberrant
      miRNA expression occurs in CSCs, such dysregulated miRNAs may be promising
      therapeutic targets. In this review, we summarize the current knowledge regarding
      miRNAs that regulate CSC properties and discuss an in vivo delivery system for
      synthetic miRNA mimics and miRNA inhibitors for the development of innovative
      miRNA therapy against CSCs. 

PMID- 25853309
TI  - Theory and practice of supersaturatable formulations for poorly soluble drugs.
AB  - Candidate compounds with high activity do not always possess adequate
      physicochemical properties to be developed as commercial products. Notably, the
      development of candidates with poor aqueous solubility has been a great challenge
      in the past two decades. Formulations that offer supersaturated state during the
      dissolution process are considered effective for increasing the oral
      bioavailability of such candidates. Representative supersaturatable dosage forms
      include amorphous solid dispersions, nanocrystal formulations and self
      (micro)emulsifying drug delivery systems. This review describes the
      characteristics of these formulations, with emphasis on the suitability of the
      candidates for each type of formulation, from a physicochemical viewpoint.
      Influence of developmental strategy on the formulation selection is also
      discussed. This review aims to provide guidance for selecting formulations for
      poorly soluble drugs based on both academic and practical backgrounds. 

PMID- 25853311
TI  - Macrophages as nanoparticle delivery vectors for photothermal therapy of brain
      tumors.
AB  - Certain types of stem and immune cells, which have an innate ability to target
      and infiltrate tumors, can be utilized as vectors to deliver several types of
      anticancer agents. In particular monocytes have the advantage of carrying
      relatively large payloads of therapeutic nanomaterials, can be patient derived in
      large numbers and are able to actively infiltrate tumors despite many barriers
      often present in the microenvironment. Monocytes can selectively cross the
      compromised blood-brain barrier surrounding brain tumors and are known to
      actively migrate to hypoxic tumor regions. Of particular interest is the
      observation that, following near-infrared exposure of tumors containing gold
      nanoshell-loaded macrophages, sufficient hyperthermia can be generated to
      suppress tumor growth. Collectively, these findings demonstrate the potential of
      monocytes as nanoparticle delivery vectors for several types of site specific
      light-based cancer therapies. 

PMID- 25853310
TI  - Delivery of local therapeutics to the brain: working toward advancing treatment
      for malignant gliomas.
AB  - Malignant gliomas, including glioblastoma and anaplastic astrocytomas, are
      characterized by their propensity to invade surrounding brain parenchyma, making
      curative resection difficult. These tumors typically recur within two centimeters
      of the resection cavity even after gross total removal. As a result, there has
      been an emphasis on developing therapeutics aimed at achieving local disease
      control. In this review, we will summarize the current developments in the
      delivery of local therapeutics, namely direct injection, convection-enhanced
      delivery and implantation of drug-loaded polymers, as well as the application of
      these therapeutics in future methods including microchip drug delivery and local
      gene therapy. 

PMID- 25853313
TI  - The general AMBER force field (GAFF) can accurately predict thermodynamic and
      transport properties of many ionic liquids.
AB  - We have applied molecular dynamics to calculate thermodynamic and transport
      properties of a set of 19 room-temperature ionic liquids. Since accurately
      simulating the thermophysical properties of solvents strongly depends upon the
      force field of choice, we tested the accuracy of the general AMBER force field,
      without refinement, for the case of ionic liquids. Electrostatic point charges
      were developed using ab initio calculations and a charge scaling factor of 0.8 to
      more accurately predict dynamic properties. The density, heat capacity, molar
      enthalpy of vaporization, self-diffusivity, and shear viscosity of the ionic
      liquids were computed and compared to experimentally available data, and good
      agreement across a wide range of cation and anion types was observed. Results
      show that, for a wide range of ionic liquids, the general AMBER force field, with
      no tuning of parameters, can reproduce a variety of thermodynamic and transport
      properties with similar accuracy to that of other published, often IL-specific,
      force fields. 

PMID- 25853312
TI  - Potent and tumor specific: arming bacteria with therapeutic proteins.
AB  - Bacteria are perfect vessels for targeted cancer therapy. Conventional
      chemotherapy is limited by passive diffusion, and systemic administration causes
      severe side effects. Bacteria can overcome these obstacles by delivering
      therapeutic proteins specifically to tumors. Bacteria have been modified to
      produce proteins that directly kill cells, induce apoptosis via signaling
      pathways, and stimulate the immune system. These three modes of bacterial
      treatment have all been shown to reduce tumor growth in animal models. Bacteria
      have also been designed to convert nontoxic prodrugs to active therapeutic
      compounds. The ease of genetic manipulation enables creation of arrays of
      bacteria that release many new protein drugs. This versatility will allow
      targeting of multiple cancer pathways and will establish a platform for
      individualized cancer medicine. 

PMID- 25853314
TI  - Rates of chemical cleavage of DNA and RNA oligomers containing guanine oxidation
      products.
AB  - The nucleobase guanine in DNA (dG) and RNA (rG) has the lowest standard reduction
      potential of the bases, rendering it a major site of oxidative damage in these
      polymers. Mapping the sites at which oxidation occurs in an oligomer via chemical
      reagents utilizes hot piperidine for cleaving oxidized DNA and aniline (pH 4.5)
      for cleaving oxidized RNA. In the present studies, a series of time-dependent
      cleavages of DNA and RNA strands containing various guanine lesions were examined
      to determine the strand scission rate constants. The guanine base lesions 8-oxo
      7,8-dihydroguanine (OG), spiroiminodihydantoin (Sp), 5-guanidinohydantoin (Gh),
      2,2,4-triamino-2H-oxazol-5-one (Z), and 5-carboxamido-5-formamido-2
      iminohydantoin (2Ih) were evaluated in piperidine-treated DNA and aniline-treated
      RNA. These data identified wide variability in the chemical lability of the
      lesions studied in both DNA and RNA. Further, the rate constants for cleaving
      lesions in RNA were generally found to be significantly smaller than for lesions
      in DNA. The OG nucleotides were poorly cleaved in DNA and RNA; Sp nucleotides
      were slowly cleaved in DNA and did not cleave significantly in RNA; Gh and Z
      nucleotides cleaved in both DNA and RNA at intermediate rates; and 2Ih
      oligonucleotides cleaved relatively quickly in both DNA and RNA. The data are
      compared and contrasted with respect to future experimental design.

PMID- 25853315
TI  - Site-specific bioconjugation of an organometallic electron mediator to an enzyme
      with retained photocatalytic cofactor regenerating capacity and enzymatic
      activity.
AB  - Photosynthesis consists of a series of reactions catalyzed by redox enzymes to
      synthesize carbohydrates using solar energy. In order to take the advantage of
      solar energy, many researchers have investigated artificial photosynthesis
      systems mimicking the natural photosynthetic enzymatic redox reactions. These
      redox reactions usually require cofactors, which due to their high cost become a
      key issue when constructing an artificial photosynthesis system. Combining a
      photosensitizer and an Rh-based electron mediator (RhM) has been shown to
      photocatalytically regenerate cofactors. However, maintaining the high
      concentration of cofactors available for efficient enzymatic reactions requires a
      high concentration of the expensive RhM; making this process cost prohibitive. We
      hypothesized that conjugation of an electron mediator to a redox enzyme will
      reduce the amount of electron mediators necessary for efficient enzymatic
      reactions. This is due to photocatalytically regenerated NAD(P)H being readily
      available to a redox enzyme, when the local NAD(P)H concentration near the enzyme
      becomes higher. However, conventional random conjugation of RhM to a redox enzyme
      will likely lead to a substantial loss of cofactor regenerating capacity and
      enzymatic activity. In order to avoid this issue, we investigated whether
      bioconjugation of RhM to a permissive site of a redox enzyme retains cofactor
      regenerating capacity and enzymatic activity. As a model system, a RhM was
      conjugated to a redox enzyme, formate dehydrogenase obtained from Thiobacillus
      sp. KNK65MA (TsFDH). A RhM-containing azide group was site-specifically
      conjugated to p-azidophenylalanine introduced to a permissive site of TsFDH via a
      bioorthogonal strain-promoted azide-alkyne cycloaddition and an appropriate
      linker. The TsFDH-RhM conjugate exhibited retained cofactor regenerating capacity
      and enzymatic activity. 

PMID- 25853316
TI  - Potential of Start Codon Targeted (SCoT) markers to estimate genetic diversity
      and relationships among Chinese Elymus sibiricus accessions.
AB  - Elymus sibiricus as an important forage grass and gene pool for improving cereal
      crops, that is widely distributed in West and North China. Information on its
      genetic diversity and relationships is limited but necessary for germplasm
      collection, conservation and future breeding. Start Codon Targeted (SCoT) markers
      were used for studying the genetic diversity and relationships among 53 E.
      sibiricus accessions from its primary distribution area in China. A total of 173
      bands were generated from 16 SCoT primers, 159 bands of which were polymorphic
      with the percentage of polymorphic bands (PPB) of 91.91%. Based upon population
      structure analysis five groups were formed. The cluster analysis separated the
      accessions into two major clusters and three sub-clusters, similar to results of
      principal coordinate analysis (PCoA). The molecular variance analysis (AMOVA)
      showed that genetic variation was greater within geographical regions (50.99%)
      than between them (49.01%). Furthermore, the study also suggested that collecting
      and evaluating E. sibiricus germplasm for major geographic regions and special
      environments broadens the available genetic base and illustrates the range of
      variation. The results of the present study showed that SCoT markers were
      efficient in assessing the genetic diversity among E. sibiricus accessions. 

PMID- 25853317
TI  - Organic-inorganic hybrid nanoparticles for bacterial inhibition: synthesis and
      characterization of doped and undoped ONPs with Ag/Au NPs.
AB  - Organic nanoparticles (ONPs) of lipoic acid and its doped derivatives ONPs/Ag and
      ONPs/Au were prepared and characterized by UV-Visible, EDS, and TEM analysis. The
      antibacterial properties of the ONPs ONPs/Ag and ONPs/Au were tested against
      bacterial strains (Staphylococcus aureus, Bacillus cereus, Escherichia coli and
      Salmonella typhi). Minimal Inhibitory Concentration (MIC) and bacterial growth
      inhibition tests show that ONPs/Ag are more effective in limiting bacterial
      growth than other NPs, particularly, for Gram positive than for Gram-negative
      ones. The order of bacterial cell growth inhibition was ONPs/Ag > ONPs > ONPs/Au.
      The morphology of the cell membrane for the treated bacteria was analyzed by SEM.
      The nature of bond formation of LA with Ag or Au was analyzed by molecular
      orbital and density of state (DOS) using DFT. 

PMID- 25853319
TI  - Ring-opening graft polymerization of propylene carbonate onto xylan in an ionic
      liquid.
AB  - The amidine organocatalyst 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) is an
      effective nucleophilic catalyst. Biocomposites with tuneable properties were
      successfully synthesized by ring-opening graft polymerization (ROGP) of propylene
      carbonate (PC) onto xylan using DBU as a catalyst in the ionic liquid (IL) 1
      allyl-3-methylimidazolium chloride ([Amim]Cl). The effects of reaction
      temperature, reaction time and the molar ratio of PC to anhydroxylose units (AXU)
      in xylan were investigated. The physico-chemical properties of xylan-graft
      poly(propylene carbonate) (xylan-g-PPC) copolymers were characterised by FT-IR,
      NMR, TGA/DTG, AFM and tensile analysis. The FT-IR and NMR results indicated the
      successful attachment of PPC onto xylan. TGA/DTG suggested the increased thermal
      stability of xylan after the attachment of PPC side chains. AFM analysis revealed
      details about the molecular aggregation of xylan-g-PPC films. The results also
      showed that with the increased DS of xylan-g-PPC copolymers, the tensile strength
      and Young's modulus of the films decreased, while the elongation at break
      increased. 

PMID- 25853318
TI  - Nanocapsular dispersion of cinnamaldehyde for enhanced inhibitory activity
      against aflatoxin production by Aspergillus flavus.
AB  - Cinnamaldehyde (CA) is marginally soluble in water, making it challenging to
      evenly disperse it in foods, and resulting in lowered anti-A. flavus efficacy. In
      the present study, nano-dispersed CA (nano-CA) was prepared to increase its
      aqueous solubility. Free and nano-dispersed CA were compared in terms of their
      inhibitory activity against fungal growth and aflatoxin production of A. flavus
      both in Sabouraud Dextrose (SD) culture and in peanut butter. Our results
      indicated that free CA inhibited the mycelia growth and aflatoxin production of
      A. flavus with a minimal inhibitory concentration (MIC) value of 1.0 mM, but
      promoted the aflatoxin production at some concentrations lower than the MIC. Nano
      CA had a lower MIC value of 0.8 mM against A. flavus, and also showed improved
      activity against aflatoxin production without the promotion at lower dose. The
      solidity of peanut butter had an adverse impact on the antifungal activity of
      free CA, whereas nano-dispersed CA showed more than 2-fold improved activity
      against the growth of A. flavus. Free CA still promoted AFB1 production at the
      concentration of 0.25 mM, whereas nano-CA showed more efficient inhibition of
      AFB1 production in the butter. 

PMID- 25853320
TI  - Two methods for increased specificity and sensitivity in loop-mediated isothermal
      amplification.
AB  - The technique of loop-mediated isothermal amplification (LAMP) utilizes four (or
      six) primers targeting six (or eight) regions within a fairly small segment of a
      genome for amplification, with concentration higher than that used in traditional
      PCR methods. The high concentrations of primers used leads to an increased
      likelihood of non-specific amplification induced by primer dimers. In this study,
      a set of LAMP primers were designed targeting the prfA gene sequence of Listeria
      monocytogenes, and dimethyl sulfoxide (DMSO) as well as Touchdown LAMP were
      employed to increase the sensitivity and specificity of the LAMP reactions. The
      results indicate that the detection limit of this novel LAMP assay with the newly
      designed primers and additives was 10 fg per reaction, which is ten-fold more
      sensitive than a commercial Isothermal Amplification Kit and hundred-fold more
      sensitive than previously reported LAMP assays. This highly sensitive LAMP assay
      has been shown to detect 11 strains of Listeria monocytogenes, and does not
      detect other Listeria species (including Listeria innocua and Listeria
      invanovii), providing some advantages in specificity over commercial Isothermal
      Amplification Kits and previously reported LAMP assay. 

PMID- 25853321
TI  - Thermal Decomposition of NCN: Shock-Tube Study, Quantum Chemical Calculations,
      and Master-Equation Modeling.
AB  - The thermal decomposition of cyanonitrene, NCN, was studied behind reflected
      shock waves in the temperature range 1790-2960 K at pressures near 1 and 4 bar.
      Highly diluted mixtures of NCN3 in argon were shock-heated to produce NCN, and
      concentration-time profiles of C atoms as reaction product were monitored with
      atomic resonance absorption spectroscopy at 156.1 nm. Calibration was performed
      with methane pyrolysis experiments. Rate coefficients for the reaction (3)NCN + M
      -> (3)C + N2 + M (R1) were determined from the initial slopes of the C atom
      concentration-time profiles. Reaction R1 was found to be in the low-pressure
      regime at the conditions of the experiments. The temperature dependence of the
      bimolecular rate coefficient can be expressed with the following Arrhenius
      equation: k1(bim) = (4.2 +/- 2.1) * 10(14) exp[-242.3 kJ mol(-1)/(RT)] cm(3) mol(
      1) s(-1). The rate coefficients were analyzed by using a master equation with
      specific rate coefficients from RRKM theory. The necessary molecular data and
      energies were calculated with quantum chemical methods up to the
      CCSD(T)/CBS//CCSD/cc-pVTZ level of theory. From the topography of the potential
      energy surface, it follows that reaction R1 proceeds via isomerization of NCN to
      CNN and subsequent C-N bond fission along a collinear reaction coordinate without
      a tight transition state. The calculations reproduce the magnitude and
      temperature dependence of the rate coefficient and confirm that reaction R1 is in
      the low-pressure regime under our experimental conditions. 

PMID- 25853322
TI  - From pair quadruple- to single-stranded helices to lines in a mixed ligand system
      via adjusting the N-substituent of L-Glu.
AB  - Utilizing the mixed-ligand strategy, a novel fourfold-interpenetrated 3D
      homochiral metal-organic framework (1) with rare pair quadruple-stranded helices
      was assembled from bpee (1,2-bis(4-pyridyl)ethylene) and NCG (N-carbamyl-l
      glutamate). Changing the carbamyl substituent of NCG with benzoyl group (NBzG: N
      benzoyl-l-glutamate), a non-interpenetrated 3D homochiral coordination polymer
      (2) composed of alternate right-handed and left-handed single helix was obtained.
      When p-tolylsulfonyl substituent was used instead, an interesting homochiral
      linear structure (3) was formed from mixed-ligand bpee and NTsG (N-p
      tolylsulfonyl-l-glutamate), with all individual NTsG being lined up orderly. The
      steric hindrance of N-substituent of l-glu has a tremendous impact on the
      construction of these diverse frameworks. Complexes 1-3 display second harmonic
      generation (SHG) efficiencies, which are approximately 0.32, 0.45, and 0.55 times
      as much as that of KDP powder. 

PMID- 25853323
TI  - [25 years after the Wall came down: psychiatry in East Germany revisited].

PMID- 25853324
TI  - [The psychiatrist's white coat is outdated - pro].

PMID- 25853325
TI  - [The psychiatrist's white coat is outdated - contra].

PMID- 25853326
TI  - [Reports from the Federal Directors' Conference].

PMID- 25853327
TI  - SNES: single nucleus exome sequencing.
AB  - Single-cell genome sequencing methods are challenged by poor physical coverage
      and high error rates, making it difficult to distinguish real biological variants
      from technical artifacts. To address this problem, we developed a method called
      SNES that combines flow-sorting of single G1/0 or G2/M nuclei, time-limited
      multiple-displacement-amplification, exome capture, and next-generation
      sequencing to generate high coverage (96%) data from single human cells. We
      validated our method in a fibroblast cell line, and show low allelic dropout and
      false-positive error rates, resulting in high detection efficiencies for single
      nucleotide variants (92%) and indels (85%) in single cells. 

PMID- 25853329
TI  - Development and Application of alpha-Heteroatom Ketones in Asymmetric Michael
      Reaction with beta-trans-Nitroalkenes.
AB  - The successful design and application of a new type of N-phenyl-imidazole
      modified alpha-heteroatom ketones in asymmetric anti-selective Michael reactions
      with beta-trans-nitroalkenes is reported. High yields and enantioselectivities
      could be obtained, and the corresponding conjugate adducts could be further
      transformed into related chiral esters and cyclopropane derivatives with
      excellent enantioselectivities. 

PMID- 25853328
TI  - Interaction of prion protein with acetylcholinesterase: potential pathobiological
      implications in prion diseases.
AB  - INTRODUCTION: The prion protein (PrP) binds to various molecular partners, but
      little is known about their potential impact on the pathogenesis of prion
      diseases RESULTS: Here, we show that PrP can interact in vitro with
      acetylcholinesterase (AChE), a key protein of the cholinergic system in neural
      and non-neural tissues. This heterologous association induced aggregation of
      monomeric PrP and modified the structural properties of PrP amyloid fibrils.
      Following its recruitment into PrP fibrils, AChE loses its enzymatic activity and
      enhances PrP-mediated cytotoxicity. Using several truncated PrP variants and
      specific tight-binding AChE inhibitors (AChEis), we then demonstrate that the PrP
      AChE interaction requires two mutually exclusive sub-sites in PrP N-terminal
      domain and an aromatic-rich region at the entrance of AChE active center gorge.
      We show that AChEis that target this site impair PrP-AChE complex formation and
      also limit the accumulation of pathological prion protein (PrPSc) in prion
      infected cell cultures. Furthermore, reduction of AChE levels in prion-infected
      heterozygous AChE knock-out mice leads to slightly but significantly prolonged
      incubation time. Finally, we found that AChE levels were altered in prion
      infected cells and tissues, suggesting that AChE might be directly associated
      with abnormal PrP. CONCLUSION: Our results indicate that AChE deserves
      consideration as a new actor in expanding pathologically relevant PrP morphotypes
      and as a therapeutic target.

PMID- 25853330
TI  - Functionalization of the PEG Corona of Nanoparticles by Clip Photochemistry in
      Water: Application to the Grafting of RGD Ligands on PEGylated USPIO Imaging
      Agent.
AB  - The fast development of nanomedicines requires more and more reliable chemical
      tools in order to accurately design materials and control the surface properties
      of the nano-objects used in biomedical applications. In this study we describe a
      smooth and simple photografting technique, i.e., the clip photochemistry, that
      allows the introduction of molecules of interest in inert polymers or on stealth
      nanoparticles directly in aqueous solution. First we developed the methodology on
      polyethylene glycol (PEG) and looked for critical parameters of the process
      (irradiation times, concentrations, washings) by using several molecular probes
      and adapted analytical techniques ((19)F qNMR, EA, LSC). We found that the clip
      photochemistry in water is a robust and efficient method to functionalize PEG.
      Second we applied it on PEGylated USPIO (USPIO-PEG) magnetic resonance imaging
      agent and succeeded in introducing RGD peptide and homemade peptidomimetics on
      their PEG segments. The magnetic abilities of the conjugated nanoparticles were
      unchanged by the derivatization process as evidenced by their relaxometric
      properties and their NMRD profile. When tested on Jurkat lymphocyte T Cells,
      which express alphavbeta3 integrins, the USPIO conjugated with RGD ligands leads
      to an increase of the transverse relaxation rate (R2) by a factor 10 to 14 as
      compared to USPIO-PEG. Consequently, it makes them good candidates for targeted
      imaging technology in cancer therapy. 

PMID- 25853331
TI  - Ischemic brain injury in hemodialysis patients: which is more dangerous,
      hypertension or intradialytic hypotension?
AB  - Abnormalities of cognitive function and high levels of depression incidence are
      characteristic of hemodialysis patients. Although previously attributed to the
      humoral effects of uremia, it is becoming increasingly appreciated that many
      elements of the overall disease state in CKD patients contribute to functional
      disturbances and physical brain injury. These factors range from those associated
      with the underlying primary diseases (cardiovascular, diabetes etc.) to those
      specifically associated with the requirement for dialysis (including consequences
      of the hemodialysis process itself). They are, however, predominantly ischemic
      threats to the integrity of brain tissue. These evolving insights are starting to
      allow nephrologists to appreciate the potential biological basis of dependency
      and depression in our patients, as well as develop and test new therapeutic
      approaches to this increasingly prevalent and important issue. This review aims
      to summarize the current understanding of brain injury in this setting, as well
      as examine recent advances being made in the modification of dialysis-associated
      brain injury. 

PMID- 25853332
TI  - APOL1 toxin, innate immunity, and kidney injury.
AB  - The discovery that two common APOL1 alleles were strongly associated with
      nondiabetic kidney diseases in African descent populations led to hope for
      improved diagnosis and treatment. Unfortunately, we still do not have a clear
      understanding of the biological function played by APOL1 in podocytes or other
      kidney cells, nor how the renal risk alleles initiate the development of
      nephropathies. Important clues for APOL1 function may be gleaned from the natural
      defense mechanism of APOL1 against trypanosome infections and from similar
      proteins (e.g., diphtheria toxin, mammalian Bcl-2 family members). This review
      provides an update on the biological functions for circulating (trypanosome
      resistance) and intracellular (emerging role for autophagy) APOL1. Further, we
      introduce a multimer model for APOL1 in kidney cells that reconciles the gain-of
      function variants with the recessive inheritance pattern of APOL1 renal risk
      alleles. 

PMID- 25853333
TI  - Phenotype standardization for drug-induced kidney disease.
AB  - Drug-induced kidney disease is a frequent cause of renal dysfunction; however,
      there are no standards to identify and characterize the spectrum of these
      disorders. We convened a panel of international, adult and pediatric,
      nephrologists and pharmacists to develop standardized phenotypes for drug-induced
      kidney disease as part of the phenotype standardization project initiated by the
      International Serious Adverse Events Consortium. We propose four phenotypes of
      drug-induced kidney disease based on clinical presentation: acute kidney injury,
      glomerular, tubular, and nephrolithiasis, along with the primary and secondary
      clinical criteria to support the phenotype definition, and a time course based on
      the KDIGO/AKIN definitions of acute kidney injury, acute kidney disease, and
      chronic kidney disease. Establishing causality in drug-induced kidney disease is
      challenging and requires knowledge of the biological plausibility for the
      specific drug, mechanism of injury, time course, and assessment of competing risk
      factors. These phenotypes provide a consistent framework for clinicians,
      investigators, industry, and regulatory agencies to evaluate drug nephrotoxicity
      across various settings. We believe that this is the first step to recognizing
      drug-induced kidney disease and developing strategies to prevent and manage this
      condition. 

PMID- 25853334
TI  - Common histological patterns in glomerular epithelial cells in secondary focal
      segmental glomerulosclerosis.
AB  - Parietal epithelial cells (PECs) are involved in the development of sclerotic
      lesions in primary focal and segmental glomerulosclerosis (FSGS). Here, the role
      of PECs was explored in the more common secondary FSGS lesions in 68 patient
      biopsies, diagnosed with 11 different frequently or rarely encountered glomerular
      pathologies and additional secondary FSGS lesions. For each biopsy, one section
      was quadruple stained for PECs (ANXA3), podocytes (synaptopodin), PEC matrix
      (LKIV69), and Hoechst (nuclei), and a second was quadruple stained for activated
      PECs (CD44 and cytokeratin-19), PEC matrix, and nuclei. In all lesions, cellular
      adhesions (synechiae) between Bowman's capsule and the tuft were formed by cells
      expressing podocyte and/or PEC markers. Cells expressing PEC markers were
      detected in all FSGS lesions independent of the underlying glomerular disease and
      often stained positive for markers of activation. Small FSGS lesions, which were
      hardly identified on PAS sections previously, were detectable by
      immunofluorescent staining using PEC markers, potentially improving the
      diagnostic sensitivity to identify these lesions. Thus, similar patterns of cells
      expressing podocyte and/or PEC markers were found in the formation of secondary
      FSGS lesions independent of the underlying glomerular disease. Hence, our
      findings support the hypothesis that FSGS lesions follow a final cellular pathway
      to nephron loss that includes involvement of cells expressing PEC markers. 

PMID- 25853336
TI  - Biotin-triggered decomposable immunomagnetic beads for capture and release of
      circulating tumor cells.
AB  - Isolation of rare, pure, and viable circulating tumor cells (CTCs) provides a
      significant insight in early cancer diagnosis, and release of captured CTCs
      without damage for ex vivo culture may offer an opportunity for personalized
      cancer therapy. In this work, we described a biotin-triggered decomposable
      immunomagnetic system, in which peptide-tagged antibody designed by chemical
      conjugation was specifically immobilized on engineered protein-coated magnetic
      beads. The interaction between peptide and engineered protein can be reversibly
      destroyed by biotin treatment, making capture and release of CTCs possible.
      Furthermore, the peptide could mediate multiple antibodies' coimmobilization on
      engineered protein-coated magnetic beads, by which capture efficiency for CTCs
      was obviously improved. Quantitative results showed that 70% of captured cells
      could be released by biotin addition, and 85% of released cells remained viable.
      In addition, 79% of cancer cells spiked in human whole blood were captured and
      could also be successfully released for culture. Finally, immunomagnetic beads
      simultaneously loaded with anti-EpCAM, anti-HER2, and anti-EGFR were successfully
      applied to isolate and detect CTCs in 17 cancer patients' peripheral blood
      samples, and 2-215 CTCs were identified with high purity. These results suggest
      that our method is reliable and has great potential in CTC detection for CTC
      based molecular profiling, diagnosis, and therapy. 

PMID- 25853335
TI  - Deceased donor multidrug resistance protein 1 and caveolin 1 gene variants may
      influence allograft survival in kidney transplantation.
AB  - Variants in donor multidrug resistance protein 1 (ABCB1) and caveolin 1 (CAV1)
      genes are associated with renal allograft failure after transplantation in
      Europeans. Here we assessed transplantation outcomes of kidneys from 368 African
      American (AA) and 314 European American (EA) deceased donors based on 38 single
      nucleotide polymorphisms (SNPs) spanning ABCB1 and 16 SNPs spanning CAV1,
      including previously associated index and haplotype-tagging SNPs. Tests for
      association with time to allograft failure were performed for the 1233 resultant
      kidney transplantations, adjusting for recipient age, sex, ethnicity, cold
      ischemia time, panel reactive antibody, human leukocyte antigen match, expanded
      criteria donation, and APOL1-nephropathy variants in AA donors. Interaction
      analyses between APOL1 with ABCB1 and CAV1 were performed. In a meta-analysis of
      all transplantations, ABCB1 index SNP rs1045642 was associated with time to
      allograft failure and other ABCB1 SNPs were nominally associated, but not CAV1
      SNPs. ABCB1 SNP rs1045642 showed consistent effects with the 558 transplantations
      from EA donors, but not with the 675 transplantations from AA donors. ABCB1 SNP
      rs956825 and CAV1 SNP rs6466583 interacted with APOL1 in transplants from AA
      donors. Thus, the T allele at ABCB1 rs1045642 is associated with shorter renal
      allograft survival for kidneys from American donors. Interactions between ABCB1
      and CAV1 with APOL1 may influence allograft failure for transplanted kidneys from
      AA donors. 

PMID- 25853338
TI  - Treatment of Collagen-Induced Arthritis Using Immune Modulatory Properties of
      Human Mesenchymal Stem Cells.
AB  - Mesenchymal stem cells (MSCs) have immune modulatory properties. We investigated
      the potential therapeutic effects of human bone marrow (BM)-, adipose tissue (AD)
      , and cord blood (CB)-derived MSCs in an experimental animal model of rheumatoid
      arthritis (RA) and explored the mechanism underlying immune modulation by MSCs.
      We evaluated the therapeutic effect of clinically available human BM-, AD-, and
      CB-derived MSCs in DBA/1 mice with collagen-induced arthritis (CIA). CIA mice
      were injected intraperitoneally with three types of MSCs. Treatment control
      animals were injected with 35 mg/kg methotrexate (MTX) twice weekly. Clinical
      activity in CIA mice, degree of inflammation, cytokine expression in the joint,
      serum cytokine levels, and regulatory T cells (Tregs) were evaluated. Mice
      treated with human BM-, AD-, and CB-MSCs showed significant improvement in
      clinical joint score, comparable to MTX-treated mice. Histologic examination
      showed greatly reduced joint inflammation and damage in MSC-treated mice compared
      with untreated mice. Microcomputed tomography also showed little joint damage in
      the MSC-treated group. MSCs significantly decreased serum interleukin (IL)-1beta,
      tumor necrosis factor (TNF)-alpha, IL-6, and interferon-gamma and increased IL-10
      and transforming growth factor-beta levels. Tregs were increased in mice treated
      with MSCs compared to untreated or MTX-treated mice. Human BM-, AD-, and CB-MSCs
      significantly suppressed joint inflammation in CIA mice. The cells decreased
      proinflammatory cytokines and upregulated anti-inflammatory cytokines and induced
      Tregs. Therefore, our study suggests that the use of human BM-, AD-, and CB-MSCs
      could be an effective therapeutic approach for RA.

PMID- 25853337
TI  - Macroscopic and macromolecular specificity of alkylphenol anesthetics for
      neuronal substrates.
AB  - We used a photoactive general anesthetic called meta-azi-propofol (AziPm) to test
      the selectivity and specificity of alkylphenol anesthetic binding in mammalian
      brain. Photolabeling of rat brain sections with [(3)H]AziPm revealed widespread
      but heterogeneous ligand distribution, with [(3)H]AziPm preferentially binding to
      synapse-dense areas compared to areas composed largely of cell bodies or myelin.
      With [(3)H]AziPm and propofol, we determined that alkylphenol general anesthetics
      bind selectively and specifically to multiple synaptic protein targets. In
      contrast, the alkylphenol anesthetics do not bind to specific sites on abundant
      phospholipids or cholesterol, although [(3)H]AziPm shows selectivity for
      photolabeling phosphatidylethanolamines. Together, our experiments suggest that
      alkylphenol anesthetic substrates are widespread in number and distribution,
      similar to those of volatile general anesthetics, and that multi-target
      mechanisms likely underlie their pharmacology. 

PMID- 25853339
TI  - Diacerein niosomal gel for topical delivery: development, in vitro and in vivo
      assessment.
AB  - The purpose of this study was to load diacerein (DCR) in niosomes by applying
      response surface methodology and incorporate these niosomes in gel base for
      topical delivery. Box-Behnken design was used to investigate the effect of charge
      inducing agent (X1), surfactant HLB (X2) and sonication time (X3) on the vesicle
      size (Y1), entrapment efficiency (Y2) and cumulative drug released (Y3). DCR
      niosomal formulations were prepared by thin film hydration method. The optimized
      formula was incorporated in different gel bases. DCR niosomal gels were evaluated
      for homogeneity, rheological behavior; in vitro release and pharmacodynamic
      activity by carrageenan-induced hind paw edema method in the rat compared with
      DCR commercial gel. The results revealed that the mean vesicle sizes of the
      prepared niosomes ranged from 7.33 to 23.72 um and the entrapment efficiency
      ranged from 9.52% to 58.43% with controlled release pattern over 8 h. DCR
      niosomal gels exhibited pseudoplastic flow with thixotropic behavior. The
      pharmacodynamic activity of DCR niosomal gel in 3% HPMC showed significant,
      37.66%, maximum inhibition of edema size in comparison with 20.83% for the
      commercial gel (p < 0.05). These results recommended the incorporation of DCR
      niosomes in 3% HPMC for topical application as a potent anti-inflammatory drug
      for the treatment of osteoarthritis. 

PMID- 25853340
TI  - PEGylated liposomes of anastrozole for long-term treatment of breast cancer: in
      vitro and in vivo evaluation.
AB  - The aim of present study was to develop conventional and PEGylated (long
      circulating), liposomes containing anastrozole (ANS) for effective treatment of
      breast cancer. ANS is a third-generation non-steroidal aromatase inhibitor of the
      triazole class used for the treatment of advanced and late-stage breast cancer in
      post-menopausal women. Under such disease conditions the median duration of
      therapy should be prolonged until tumor regression ends (>31 months). Liposomes
      were prepared by the thin film hydration method by using ANS and various lipids
      such as soyaphosphatidyl choline, cholesterol and methoxy polyethylene glycol
      distearoyl ethanolamine in different concentration ratios and evaluated for
      physical characteristics, in vitro drug release and stability. Optimized
      formulations of liposome were studied for in vitro cytotoxic activity against the
      BT-549 and MCF-7 cell lines and in vivo behavior in Wistar rats. Preformulation
      studies, both Fourier transform infrared study and differential scanning
      calorimetry analysis showed no interaction between the drug and the excipients
      used in the formulations. The optimized formulations AL-07 and AL-09 liposomes
      showed encapsulation efficiencies in the range 65.12 +/- 1.05% to 69.85 +/- 3.2%
      with desired mean particle size distribution of 101.1 +/- 5.9 and 120.2 +/- 2.8
      nm and zeta potentials of -43.7 +/- 4.7 and -62.9 +/- 3.5 mV. All the optimized
      formulations followed Higuchi-matrix release kinetics and when plotted in
      accordance with the Korsemeyer-Peppas method, the n-value 0.5 < n < 1.0 suggests
      an anomalous (non-Fickian) transport. Likewise, the PEGylated liposomes showed
      greater tumor growth inhibition on BT-549 and MCF-7 cell lines from in vitro
      cytotoxicity studies (p < 0.05). Pharmacokinetic study of conventional and
      PEGylated liposomes in Wistar rats demonstrated a 3.33- and 20.28-fold increase
      in AUC(0-infinity) values when compared to pure drug (p < 0.001). Among the
      formulations, PEGylated liposomes showed encouraging results by way of their long
      circulation and sustained delivery properties for effective treatment of breast
      cancer. 

PMID- 25853341
TI  - Study of permeation and blocker binding in TMEM16A calcium-activated chloride
      channels.
AB  - We studied the effects of mutations of positively charged amino acid residues in
      the pore of X. tropicalis TMEM16A calcium-activated chloride channels: K613E,
      K628E, K630E; R646E and R761E. The activation and deactivation kinetics were not
      affected, and only K613E showed a lower current density. K628E and R761E affect
      anion selectivity without affecting Na(+) permeation, whereas K613E, R646E and
      the double mutant K613E + R646E affect anion selectivity and permeability to
      Na(+). Furthermore, altered blockade by the chloride channel blockers anthracene
      9-carboxylic acid (A-9-C), 4, 4'-Diisothiocyano-2,2'-stilbenedisulfonic acid
      (DIDS) and T16inh-A01 was observed. These results suggest the existence of 2
      binding sites for anions within the pore at electrical distances of 0.3 and 0.5.
      These sites are also relevant for anion permeation and blockade. 

PMID- 25853342
TI  - Using a sequential regimen to eliminate bacteria at sublethal antibiotic dosages.
AB  - We need to find ways of enhancing the potency of existing antibiotics, and, with
      this in mind, we begin with an unusual question: how low can antibiotic dosages
      be and yet bacterial clearance still be observed? Seeking to optimise the
      simultaneous use of two antibiotics, we use the minimal dose at which clearance
      is observed in an in vitro experimental model of antibiotic treatment as a
      criterion to distinguish the best and worst treatments of a bacterium,
      Escherichia coli. Our aim is to compare a combination treatment consisting of two
      synergistic antibiotics to so-called sequential treatments in which the choice of
      antibiotic to administer can change with each round of treatment. Using
      mathematical predictions validated by the E. coli treatment model, we show that
      clearance of the bacterium can be achieved using sequential treatments at
      antibiotic dosages so low that the equivalent two-drug combination treatments are
      ineffective. Seeking to treat the bacterium in testing circumstances, we
      purposefully study an E. coli strain that has a multidrug pump encoded in its
      chromosome that effluxes both antibiotics. Genomic amplifications that increase
      the number of pumps expressed per cell can cause the failure of high-dose
      combination treatments, yet, as we show, sequentially treated populations can
      still collapse. However, dual resistance due to the pump means that the
      antibiotics must be carefully deployed and not all sublethal sequential
      treatments succeed. A screen of 136 96-h-long sequential treatments determined
      five of these that could clear the bacterium at sublethal dosages in all
      replicate populations, even though none had done so by 24 h. These successes can
      be attributed to a collateral sensitivity whereby cross-resistance due to the
      duplicated pump proves insufficient to stop a reduction in E. coli growth rate
      following drug exchanges, a reduction that proves large enough for appropriately
      chosen drug switches to clear the bacterium. 

PMID- 25853344
TI  - An end to the culture of silence in the NHS: the Francis review.

PMID- 25853345
TI  - Calling time on the Cancer Drugs Fund? Funding the NHS in the age of austerity.

PMID- 25853346
TI  - The Five year forward view: issues of funding and the ageing population still
      need addressing.

PMID- 25853347
TI  - A clinician's guide to cardiopulmonary exercise testing 1: an introduction.
AB  - Compared to standard exercise tolerance testing, cardiopulmonary exercise testing
      is a reliable and powerful tool that can be used for risk stratification,
      exercise prescription and clinical diagnosis. 

PMID- 25853343
TI  - Cytosolic Hsp70 and co-chaperones constitute a novel system for tRNA import into
      the nucleus.
AB  - tRNAs are unique among various RNAs in that they shuttle between the nucleus and
      the cytoplasm, and their localization is regulated by nutrient conditions.
      Although nuclear export of tRNAs has been well documented, the import machinery
      is poorly understood. Here, we identified Ssa2p, a major cytoplasmic Hsp70 in
      Saccharomyces cerevisiae, as a tRNA-binding protein whose deletion compromises
      nuclear accumulation of tRNAs upon nutrient starvation. Ssa2p recognizes several
      structural features of tRNAs through its nucleotide-binding domain, but prefers
      loosely-folded tRNAs, suggesting that Ssa2p has a chaperone-like activity for
      RNAs. Ssa2p also binds Nup116, one of the yeast nucleoporins. Sis1p and Ydj1p,
      cytoplasmic co-chaperones for Ssa proteins, were also found to contribute to the
      tRNA import. These results unveil a novel function of the Ssa2p system as a tRNA
      carrier for nuclear import by a novel mode of substrate recognition. Such Ssa2p
      mediated tRNA import likely contributes to quality control of cytosolic tRNAs. 

PMID- 25853348
TI  - Assessment of an incidental finding of left bundle-branch block.
AB  - Incidental left bundle-branch block occurs in up to 1.5% of healthy adults
      without symptoms or signs of cardiovascular disease. It may be found during
      investigation for non-cardiac disease, during preoperative assessment, private
      health screening or inpatient monitoring. This article outlines how to assess
      these patients. 

PMID- 25853349
TI  - Obstructive sleep apnoea associated with syringomyelia.
AB  - Coexistence of obstructive sleep apnoea and syringomyelia is quite rare. This
      article discusses three cases of coexisting obstructive sleep apnoea and
      syringomyelia and looks at the possible mutual influences between the two
      diseases. 

PMID- 25853351
TI  - Breast reconstruction: one size does not fit all.

PMID- 25853350
TI  - Splenic injury: diagnosis and management.
AB  - Better understanding of the dual functionality of the spleen has led to a
      conservative approach to splenic trauma. With accurate assessment and vigilant
      clinical examination up to two thirds of splenic injuries can be managed
      expectantly; when surgery is unavoidable, splenic preserving techniques may be
      used to maintain function. 

PMID- 25853352
TI  - Implant-based breast reconstruction with meshes and matrices: biological vs
      synthetic.
AB  - This article presents an overview of the different acellular dermal matrices and
      synthetic meshes used in modern-day primary and secondary implant-based breast
      reconstruction. Case examples are given, along with a description of the senior
      author's pioneering direct-to-implant reconstruction. 

PMID- 25853353
TI  - PICOTM incision closure in oncoplastic breast surgery: a case series.
AB  - Single-use negative pressure wound therapy (PICOTM) has been used on high-risk
      surgically incised wounds with encouraging results, but there is no evidence for
      its use in oncoplastic breast surgery. This article reports a case series with
      closed incisions in oncoplastic breast procedures following the introduction of
      PICOTM. 

PMID- 25853354
TI  - Deprivation of Liberty Safeguards: ethical and clinical implications.
AB  - The Deprivation of Liberty Safeguards were introduced in 2009 as an addition to
      the Mental Capacity Act 2005. This review discusses the legal impact of the
      Deprivation of Liberty Safeguards in the management of incapacitated patients. 

PMID- 25853355
TI  - Medical students' perceptions of the situational judgement test: a mixed methods
      study.
AB  - The situational judgement test is a UK-based assessment tool for determining job
      allocation for exiting medical students which has been shown to be reliable and
      valid. This study assessed medical students' perceptions of the situational
      judgement test, having undergone the assessment, and reviewed the findings. 

PMID- 25853356
TI  - Clinical leadership effectiveness, change and complexity.
AB  - This article explores how an understanding of approaches to leading and managing
      change and complexity science can help clinical leaders engage with and manage
      change in complex environments and systems more effectively. 

PMID- 25853357
TI  - Successful intravenous thrombolysis following full dose rivaroxaban 5 hours
      before ictus.

PMID- 25853358
TI  - Metastatic renal carcinoma: a question of management.

PMID- 25853359
TI  - Absent inferior vena cava: an unusual cause of recurrent deep vein thrombosis.

PMID- 25853360
TI  - Sir John Tomes: father of modern dental surgery in England.

PMID- 25853361
TI  - The Five year forward view: issues of funding and the ageing population still
      need addressing.

PMID- 25853362
TI  - Tramadol-related hypoglycaemia and tramadol-induced anorexia.

PMID- 25853363
TI  - Should we be cooling patients after out of hospital cardiac arrest?

PMID- 25853364
TI  - The pupillary examination.

PMID- 25853365
TI  - A guide to magnetic resonance imaging in clinical practice.

PMID- 25853366
TI  - Overview of pancreatic resections: postoperative management.

PMID- 25853368
TI  - Photodynamic therapy: a review of applications in neurooncology and
      neuropathology.

PMID- 25853367
TI  - Dressing up Nanoparticles: A Membrane Wrap to Induce Formation of the Virological
      Synapse.
AB  - Next-generation nanoparticle-based drug delivery systems require the ability to
      target specific organelles or subcellular regions in selected target cells. Human
      immunodeficiency virus type I (HIV-1) particles are evolutionarily optimized
      nanocarriers that have evolved to avoid intracellular degradation and achieve
      enrichment at the synapse between mature dendritic cells (mDCs) and T cells by
      subverting cellular trafficking mechanisms. This study demonstrates that
      integration of the glycosphingolipid, GM3, in a membrane around a solid
      nanoparticle (NP) core is sufficient to recapitulate key aspects of the virus
      particle trafficking in mDCs. GM3-presenting artificial virus NPs (GM3-AVNs)
      accumulate in CD169(+) and CD81(+) nonlysosomal compartments in an actin
      dependent process that mimics the sequestration of HIV-1. Live-cell optical
      tracking studies reveal a preferential recruitment and arrest of surface scanning
      CD4(+) T cells in direct vicinity to the AVN-enriched compartments. The formed
      mDC-T cell conjugates exhibit strong morphological similarities between the GM3
      AVN-containing mDC-T cell synapse and the HIV-1 virological synapse, indicating
      that GM3-CD169 interactions alone are sufficient for establishing the mDC-T cell
      virological synapse. These results emphasize the potential of the GM3-AVN
      approach for providing therapeutic access to a key step of the host immune
      response--formation of the synaptic junction between an antigen-presenting cell
      (mDC) and T cells--for modulating and controlling immune responses.

PMID- 25853369
TI  - Short-term Results of a Magnetic Resonance Imaging-Based Swedish Screening
      Program for Individuals at Risk for Pancreatic Cancer.
AB  - IMPORTANCE: Pancreatic cancer is the fourth leading cause of cancer-related death
      in Western countries. In approximately 10% of all patients with pancreatic
      cancer, it is possible to define a positive family history for pancreatic cancer
      or for one of the other related genetic syndromes. A screening program for
      individuals at risk is recommended; however, surveillance modalities have not
      been defined yet. OBJECTIVE: To analyze the short-term results of a prospective
      clinical surveillance program for individuals at risk for pancreatic cancer using
      a noninvasive magnetic resonance imaging (MRI)-based screening protocol. DESIGN,
      SETTING AND PARTICIPANTS: A prospective observational study of all patients with
      a genetic risk for developing pancreatic cancer who were referred to Karolinska
      University Hospital between January 1, 2010, and January 31, 2013, using an MRI
      based surveillance program. All patients were investigated for the most common
      genetic mutations associated with pancreatic cancer. EXPOSURE: A noninvasive MRI
      based screening protocol. MAIN OUTCOMES AND MEASURES: The ability of MRI to
      identify potential precancerous or early cancers in individuals at risk for
      pancreatic cancer. RESULTS: Forty patients (24 women and 16 men) were enrolled.
      The mean age was 49.9 years. The mean length of follow-up was 12.9 months. The
      numbers of relatives affected by pancreatic cancer were 5 in 2 patients (5%), 4
      in 5 patients (12.5%), 3 in 17 patients (42.5%), 2 in 14 patients (35%), and 1 in
      2 patients (5%). In 4 patients (10%), a p16 mutation was found; in 3, a BRCA2
      mutation (7.5%); and in 1, a BRCA1 mutation (2.5%). In 16 patients (40%), MRI
      revealed a pancreatic lesion: intraductal papillary mucinous neoplasia (14
      patients, 35%) and pancreatic ductal adenocarcinoma (2 patients, 5%). One patient
      had a synchronous intraductal papillary mucinous neoplasia and pancreatic ductal
      adenocarcinoma. Five patients (12.5%) required surgery (3 for pancreatic ductal
      adenocarcinoma and 2 for intraductal papillary mucinous neoplasia), while the
      remaining 35 are under continued surveillance. CONCLUSIONS AND RELEVANCE: During
      a median follow-up of approximately 1 year, pancreatic lesions were detected in
      40% of the patients, of whom 5 underwent surgery. Although the study time was
      relatively short, the surveillance program in individuals at risk seems to be
      effective.

PMID- 25853370
TI  - Effects of acute doses of prosocial drugs methamphetamine and alcohol on plasma
      oxytocin levels.
AB  - Many drugs, including alcohol and stimulants, demonstrably increase sociability
      and verbal interaction and are recreationally consumed in social settings. One
      drug, 3,4-methylenedioxymethamphetamine (MDMA, ecstasy), seems to produce its
      prosocial effects by increasing plasma oxytocin levels, and the oxytocin system
      has been implicated in responses to several other drugs of abuse. Here, we sought
      to investigate the effects of 2 other "social" drugs on plasma oxytocin levels-
      methamphetamine and alcohol. Based on their shared capacity to enhance
      sociability, we hypothesized that both methamphetamine and alcohol would increase
      plasma oxytocin levels. In study 1, 11 healthy adult volunteers attended 3
      sessions during which they received methamphetamine (10 mg or 20 mg) or placebo
      under double-blind conditions. Subjective drug effects, cardiovascular effects,
      and plasma oxytocin levels were measured at regular intervals throughout the
      sessions. In study 2, 8 healthy adult volunteers attended a single session during
      which they received 1 beverage containing placebo, and then a beverage containing
      alcohol (0.8 g/kg). Subjective effects, breath alcohol levels, and plasma
      oxytocin levels were measured at regular intervals. Both methamphetamine and
      alcohol produced their expected physiological and subjective effects, but neither
      of these drugs increased plasma oxytocin levels. The neurobiological mechanisms
      mediating the prosocial effects of drugs such as alcohol and methamphetamine
      remain to be identified.

PMID- 25853371
TI  - The prevalence of lithium-associated hyperparathyroidism in a large Swedish
      population attending psychiatric outpatient units.
AB  - OBJECTIVE: This retrospective study determined the prevalence of lithium
      associated hyperparathyroidism (LHPT) in 2 geographically defined, equivalent
      populations in Sweden, with no other selection bias. METHODS: The medical
      journals of all patients receiving lithium treatment were examined specifically
      regarding their biochemistry: calcium, parathyroid hormone (PTH), creatinine, and
      vitamin D. The condition LHPT was defined biochemically. All patient data were
      noted, and the prevalence of the condition could thereby be calculated. RESULTS:
      A total of 423 patients were included (251 women and 172 men; 3:2), treated over
      a mean of 13.5 years (range, 1-46 years), aged 19 to 92. 77 patients (18%) were
      identified with LHTP whose median serum calcium was 2.55 mmol/L and PTH was 99
      ng/L. A further 21% showed tendencies toward hypercalcemia. Forty-three percent
      had vitamin D insufficiency. Five patients (approximately 1%) had undergone
      parathyroidectomy. CONCLUSION: The prevalence of LHPT is high and often goes
      undetected. Vitamin D insufficiency is common as is polypharmacy. Surgery, for
      unclear reasons, has not been performed extensively, possibly because of limited
      knowledge of the underlying pathophysiology or surgery's significance. We present
      standard recommendations on patient management and suggest continual, specific
      follow-up including the monitoring of calcium, PTH, and vitamin D at least
      annually. Surgery should be considered with intention to improve psychiatric well
      being and provide multiorgan protection.

PMID- 25853372
TI  - Rapid Fingerprint Analysis of Plant Extracts for Ellagitannins, Gallic Acid, and
      Quinic Acid Derivatives and Quercetin-, Kaempferol- and Myricetin-Based Flavonol
      Glycosides by UPLC-QqQ-MS/MS.
AB  - This paper describes the development of a rapid method with ultraperformance
      liquid chromatography-triple-quadrupole mass spectrometry that can specifically
      measure group-specific fingerprints from plant extracts for the following
      polyphenol groups: (1) ellagitannins, (2) gallic acid derivatives, (3) quinic
      acid derivatives, (4) quercetin-based flavonol glycosides, (5) kaempferol-based
      flavonol glycosides, and (6) myricetin-based flavonol glycosides. In addition,
      the method records simultaneously diode array and full scan mass spectrometry
      data that can be used to later characterize and quantify the main individual
      polyphenols if necessary. All of this is achieved within the 10 min period of
      analysis, which makes the presented method a significant addition to the
      chemistry tools currently available for the rapid analysis of complex polyphenol
      mixtures from plant extracts. 

PMID- 25853373
TI  - Indeed, why wound care?

PMID- 25853374
TI  - Nutrition 411: Exercising to improve body composition.

PMID- 25853375
TI  - The alliance of wound care stakeholders: advocating for wound care.

PMID- 25853376
TI  - A cross-sectional pilot study to examine food sufficiency and assess nutrition
      among low-income patients with injection-related venous ulcers.
AB  - Adequate nutrition has long been considered a critical component for wound
      healing, but literature regarding the relationship between nutrition and venous
      ulcer (VU) healing is limited. A person's nutrition is affected by the
      availability of food as well as his/her overall health. Food sufficiency and
      nutrition are important concerns in the care of persons of low income with
      injection-related VUs, which tend to be large and slow to heal. A cross-sectional
      pilot study was conducted to explore the relationship between food
      sufficiency/security and nutrition with regard to demographic, wound, quality-of
      life, physical activity, falls, and fall risk variables. Nutrition was examined
      using 2 well-developed instruments that measure food sufficiency/security and
      assess nutrition--the United States Department of Agriculture's Adult Food
      Sufficiency Questionnaire (FSQ) and the Nestle Mini Nutritional Assessment (MNA).
      All participants (N = 31, 54% men, mean age 56.1 +/- 3.6 years, all African
      American) were recruited from an outpatient clinic. All had injection-related VUs
      from a history of injecting illicit substances. In terms of food
      sufficiency/security, most participants (26, 84%) reported having enough food in
      the house, but 10 (32%) worried about running out of food. From 16% to 22.6% of
      participants expressed concern with food sufficiency/security in terms of cutting
      meal size, eating less, hunger, and weight loss. Food sufficiency/security was
      high for 19 (61.3%), but 12 (39%) had marginal or lower food
      sufficiency/security. MNA scores showed 16 participants (52%) were at risk of
      malnutrition or malnourished. Low food sufficiency/security was significantly (P
      <0.05) associated with less motivation for activity (r = -0.40) and less walking
      (r = -0.36). Better nutrition assessment scores were significantly associated (P
      <0.01) with fewer comorbidities (r = -0.57) and falls (r = -0.46) and with higher
      quality of life (r = 0.50), motivation for physical activity (r = 0.59), and
      balance confidence (r = 0.60). Both food security and nutrition assessment are
      important to assess in low-income persons with injection-related VUs. A number of
      significant relationships of the FSQ and MNA to other variables was found but
      needs further investigation with a larger sample.

PMID- 25853377
TI  - Pressure ulcer prevention algorithm content validation: a mixed-methods,
      quantitative study.
AB  - Translating pressure ulcer prevention (PUP) evidence-based recommendations into
      practice remains challenging for a variety of reasons, including the perceived
      quality, validity, and usability of the research or the guideline itself.
      Following the development and face validation testing of an evidence-based PUP
      algorithm, additional stakeholder input and testing were needed. Using
      convenience sampling methods, wound care experts attending a national wound care
      conference and a regional wound ostomy continence nursing (WOCN) conference
      and/or graduates of a WOCN program were invited to participate in an Internal
      Review Board-approved, mixed-methods quantitative survey with qualitative
      components to examine algorithm content validity. After participants provided
      written informed consent, demographic variables were collected and participants
      were asked to comment on and rate the relevance and appropriateness of each of
      the 26 algorithm decision points/steps using standard content validation study
      procedures. All responses were anonymous. Descriptive summary statistics, mean
      relevance/appropriateness scores, and the content validity index (CVI) were
      calculated. Qualitative comments were transcribed and thematically analyzed. Of
      the 553 wound care experts invited, 79 (average age 52.9 years, SD 10.1; range 23
      73) consented to participate and completed the study (a response rate of 14%).
      Most (67, 85%) were female, registered (49, 62%) or advanced practice (12, 15%)
      nurses, and had > 10 years of health care experience (88, 92%). Other health
      disciplines included medical doctors, physical therapists, nurse practitioners,
      and certified nurse specialists. Almost all had received formal wound care
      education (75, 95%). On a Likert-type scale of 1 (not relevant/appropriate) to 4
      (very relevant and appropriate), the average score for the entire algorithm/all
      decision points (N = 1,912) was 3.72 with an overall CVI of 0.94 (out of 1). The
      only decision point/step recommendation with a CVI of <= 0.70 was the
      recommendation to provide medical-grade sheepskin for patients at high risk for
      friction/shear. Many positive and substantive suggestions for minor modifications
      including color, flow, and algorithm orientation were received. The high overall
      and individual item rating scores and CVI further support the validity and
      appropriateness of the PUP algorithm with the addition of the minor
      modifications. The generic recommendations facilitate individualization, and
      future research should focus on construct validation testing.

PMID- 25853378
TI  - Predictive validity and reliability of the Turkish version of the risk assessment
      pressure sore scale in intensive care patients: results of a prospective study.
AB  - Multiple pressure ulcer (PU) risk assessment instruments have been developed and
      tested, but there is no general consensus on which instrument to use for specific
      patient populations and care settings. The purpose of this study was to determine
      the reliability and predictive validity of the Turkish version of the Risk
      Assessment Pressure Sore (RAPS) instrument, which includes 12 variables--5 from
      the modified Norton Scale, 3 from the Braden Scale, and 3 from other research
      results--for use in intensive care unit (ICU) patients. The English version of
      the RAPS instrument was translated into Turkish and tested for internal
      consistency and predictive validity (sensitivity, specificity, positive
      predictive value, and negative predictive value) using a convenience sample of
      122 patients consecutively admitted to an ICU unit in Turkey. The patients were
      assessed within 24 hours of admission, and after that, once a week until the
      development of a PU or discharge from the unit. The incidence of PUs in this
      population was 23%. The majority of ulcers that developed were Stage I. Internal
      consistency of the RAPS tool was adequate (Cronbach's alpha = 0.81). The best
      balance between sensitivity and specificity for ICU patients was reached at a cut
      off point of <= 27 (ie, sensitivity = 74.2%, specificity = 31.8%, positive
      predictive value = 38.7%, and negative predictive value 91.3%). This is lower
      than the cut-off point reported in other studies of the RAPS scale. In this
      population of ICU patients, the RAPS scale was found to have acceptable
      reliability and poor validity. Additional studies to evaluate the predictive
      validity and reliability of the RAPS scale in other patient populations and care
      settings are needed.

PMID- 25853379
TI  - Using active Leptospermum honey in the debridement process: 6 challenging cases
      from the inner city.
AB  - The use of honey-based dressings has been documented for thousands of years.
      Recent studies suggest their effectiveness may be, in part, related to their
      ability to facilitate autolytic debridement. Six patients who presented with
      multiple comorbidities and risk factors for delayed healing whose wounds required
      debridement were managed with active Leptospermum honey (ALH) to evaluate the
      safety and effectiveness of this treatment modality. The 6 patients ranged in age
      from 39 to 81 years. The ALH was covered with a foam dressing; both dressings
      were changed approximately every 3 days. After 9 to 20 days of use, wounds were
      completely, or almost completely, debrided, and a 75% concomitant average
      increase in the amount of granulation tissue in the wound bed was observed. No
      adverse events were noted. The use of ALH in this case series was effective, and
      no surgical debridement was needed. Research to compare the efficacy of ALH to
      other debridement methods is warranted. 

PMID- 25853381
TI  - Incidence and survival of gynecologic sarcomas in England.
AB  - OBJECTIVE: Gynecologic sarcomas account for approximately 3% to 4% of all
      gynecologic malignancies and are associated with poor outcomes compared with
      gynecologic carcinomas. The aim of this study is to report the incidence and
      survival rates of the main gynecologic sarcomas using national English cancer
      registration data. METHODS/MATERIALS: Records of gynecologic sarcomas diagnosed
      between 1985 and 2008 were extracted from the English National Cancer Data
      Repository. ICD-O3 morphology codes were used to assign tumor records to specific
      histologic subgroups. Incidence and 5-year relative survival rates were
      calculated. RESULTS: There were 5316 new cases of gynecologic sarcoma diagnosed
      in England between 1985 and 2008. Incidence rates increased significantly in the
      early 1990s, probably due to coding changes. Age-specific incidence rates were
      highest in women aged between 45 and 64 years. In the most recent period studied
      (2001-2008), incidence rates fluctuated between 8 and 9.6 per million. The most
      common anatomical site was the uterus (83% of all diagnoses), and the most common
      histologic diagnosis was leiomyosarcoma (52% of all diagnoses). Overall 5-year
      relative survival increased significantly between 1985-1989 and 2000-2004, from
      34% to 48%. CONCLUSIONS: Gynecologic sarcoma incidence rates have varied little
      since 1993, whereas survival has improved significantly. These results are
      consistent with previously published small series and case studies, and provide a
      more complete picture of gynecologic sarcoma incidence and survival patterns in
      England.

PMID- 25853380
TI  - HIV Status and Acute Hematologic Toxicity Among Patients With Cervix Cancer
      Undergoing Radical Chemoradiation.
AB  - INTRODUCTION: Women infected with the human immunodeficiency virus (HIV) have a
      higher risk of developing cervix carcinoma than do other women who are thought to
      be more vulnerable to acute toxicities during chemoradiation. We compared HIV
      positive/HIV-negative patients with cervix carcinoma at a single institution with
      respect to cancer treatment toxicities. METHODS AND MATERIALS: Among patients
      with stage Ib1-IIIb invasive cervical carcinoma who received radiation or
      chemoradiation with curative intent, we evaluated demographic and clinical
      characteristics of HIV-positive and HIV-negative patients. Treatment regimens
      were documented and toxicities scored as per Radiation Therapy Oncology Group
      guidelines. We developed logistic regression models for the associations of grade
      3/4 toxicities with HIV status. RESULTS: Complete data were available on 213
      patients, including 36 (16.8%) who were HIV positive. More than 85% of both HIV
      positive and HIV-negative patients received a minimum of 68-Gy equivalent dose in
      2-Gy-fraction external beam and high-dose-rate brachytherapy. More HIV-positive
      than HIV-negative patients were prescribed radiation alone (38.9% vs 24.29%, P =
      0.01), experienced at least 1 grade 3/4 toxicity (38.9% vs 26.6%), or developed
      grade 3/4 leucopenia (30.6% vs 10.2%, P = 0.003).In a multivariable model,
      patients who developed a grade 3/4 toxicity were 4 times as likely to have
      received chemotherapy (odds ratio, 4.41 [95% confidence interval, 1.76-11.1]; P =
      0.023) and twice as likely to be HIV positive (odds ratio 2.16 [95% confidence
      interval, 0.98-4.8]; P = 0.05) as women who did not experience such toxicities.
      CONCLUSIONS: HIV-positive patients with cervical carcinoma received adequate
      radiotherapy but were less likely than HIV-negative patients to complete
      chemotherapy. Few HIV-positive or HIV-negative patients who received radiotherapy
      without chemotherapy experienced grade 3/4 toxicity. However, among patients who
      received chemotherapy, those who were HIV positive were more likely than others
      to experience hematologic toxicity.

PMID- 25853382
TI  - Does Lymphadenectomy Improve Survival in Uterine Leiomyosarcoma?
AB  - INTRODUCTION: The role of lymphadenectomy in the management of uterine
      leiomyosarcoma (LMS) is controversial. We aimed to identify whether lymph node
      dissection (LND) has any survival benefit in uterine LMS. METHODS: Data of 95
      patients with histologically proven uterine LMS from 2 tertiary centers (1993
      through 2009) were retrospectively analyzed. Kaplan-Meier and Cox proportional
      hazards regression models were used for analyses. RESULTS: Mean age was 51.5
      years. Thirty-six (37.9%) underwent LND. The median lymph node count was 54.
      Eight (22.2%) patients had lymphatic metastasis. Median follow-up was 26 months.
      Sixty-two (65%) patients had recurrence and 48 (50.5%) died. Median disease-free
      survival (DFS) was 19 months for both group of patients who had or did not have
      LND, and median overall survival (OS) was 29 and 26 months, respectively (P =
      0.4). Five-year DFS was 35.9% vs 26.8% (P = 0.4), and 5-year OS was 45.4% vs
      43.8% (P = 0.22) for the groups. Multivariate analyses did not reveal a single
      independent prognostic factor in respect to DFS or OS. CONCLUSION: Higher rate of
      lymph node metastasis in patients with extrauterine disease indicated the
      importance of LND in LMS. However, the survival benefit of lymphadenectomy could
      not be shown.

PMID- 25853383
TI  - Pelvic Exenteration in Gynecologic Cancer: La Paz University Hospital Experience.
AB  - BACKGROUND: Pelvic exenteration is an ultraradical surgery involving the en bloc
      resection of the pelvic organs, including the internal reproductive organs, the
      distal urinary tract (ureters, bladder, urethra), and/or anorectum. It is mainly
      applied as a salvage surgery for recurrent gynecologic tumors of any origin
      (vulva, vagina, cervix, uterine, and also ovary). Our aim was to establish the
      most favorable cases for this type of surgery by means of a review of our
      institution experience. METHODS: Retrospective analyses of all patients treated
      with pelvic exenteration for recurrent gynecologic cancer from 2008 to 2014 at La
      Paz University Hospital. RESULTS: Ten patients underwent pelvic exenteration for
      recurrent gynecologic cancers including uterine, cervical, vaginal, vulvar, and
      ovarian cancer. All patients had received prior treatment: surgery, radiotherapy,
      and/or chemotherapy. Eight patients underwent total pelvic exenteration, one
      anterior and one posterior pelvic exenteration. Urinary diversions technique
      consisted of ileal conduits in all cases. Permanent colostomy was performed in
      all cases. Postoperative complications were related to the urinary diversion in
      50% of the cases, to the reconstructive technique in 30%, and to systemic or
      pelvic infections in 20%. CONCLUSIONS: Despite the high morbidity and mortality
      rates, pelvic exenteration is feasible, and in selected cases of cancer
      recurrence is the last possible treatment.

PMID- 25853384
TI  - Sentinel Lymph Node Biopsy in Endometrial Cancer--Comparison of 2 Detection
      Methods.
AB  - OBJECTIVES: Sentinel lymph node biopsy (SLNB) can identify patients with nodal
      metastases who are eligible for tailored treatment. The aim of study was to
      compare the SLN detection rates using cervical and subserosal administration of 2
      tracers. RESULTS: In group 1 (82 patients), SLNB was performed using radiocolloid
      injected to the cervix and blue dye administered to the fundus. In group 2, blue
      dye was injected to cervix and fundus (106 patients). Only SLNB was performed in
      128 (68.1%) women. In the remaining 60 (31.9%) patients, pelvic/para-aortic
      lymphadenectomy together with SLNB was performed. Groups 1 and 2 did not differ
      with regard to the frequencies of SLNB and lymphadenectomy. The detection rate
      for both groups was 90.9%. Bilateral detection was achieved in 72.5%. Para-aortic
      SLNs were found in 9.6%. Detection rates in groups 1 and 2 were 95.1% and 87.7%
      (P = 0.065). In comparison of cervical administration of radioisotope and
      subserosal injection of blue dye in group 1, we found a significant difference
      for total SLN detection (91.5% vs 74.4%, P < 0.05) and no significant difference
      for bilateral detection (73.3% vs 59.1%, P = 0.776). We did not find differences
      in the para-aortic SLN detection rates achieved after administration of a
      radiotracer and injection of a blue dye (4.9% vs 9.8%, P = 0.184). Eighteen
      patients (9.6%) presented with nodal disease, including 15 women with SLN
      involvement. The false-negative rate, calculated for patients subjected to
      lymphadenectomy, was 12.5% (1/8); using the SLNB surgical algorithm, it was 10%
      (1/10). CONCLUSIONS: Cervical administration of a tracer, especially
      radioisotope, results in high SLN detection rates. In turn, the subserosal
      injection can be used only as an adjuvant method for SLNB. Low para-aortic SLN
      detection rates observed after cervical administration of a tracer do not seem to
      be a serious limitation of this technique.

PMID- 25853385
TI  - Pretreatment Mean Apparent Diffusion Coefficient Is Significantly Correlated With
      Event-Free Survival in Patients With International Federation of Gynecology and
      Obstetrics Stage Ib to IIIb Cervical Cancer.
AB  - OBJECTIVES: To assess the prognostic impact of the pretreatment mean apparent
      diffusion coefficient (ADCmean) values of tumors obtained by diffusion-weighted
      magnetic resonance imaging. We evaluated the prognostic value of the ADCmean for
      event-free survival (EFS) and overall survival (OS) among patients with uterine
      cervical cancer. METHODS/MATERIALS: We included 171 patients diagnosed as having
      International Federation of Gynecology and Obstetrics stage Ib to IIIb cervical
      cancer by pretreatment magnetic resonance imaging scans, regardless of
      therapeutic methods. In all patients and in patients with squamous cell carcinoma
      (SCC; n = 123), the optimal cutoff values of the tumor ADCmean for EFS and for OS
      were determined, respectively. The prognostic significance of the ADCmean was
      evaluated using univariate and multivariate Cox regression analyses. RESULTS: In
      the univariate analyses, the ADCmean values were significantly associated with
      negative effects on EFS both in all patients and in patients with SCC, while not
      being significantly associated with OS in both groups. In the multivariate
      analysis, ADCmean was an independent biomarker for EFS (P < 0.05) in patients
      with SCC along with lymph node metastasis and definitive surgery, whereas ADCmean
      was not independently significant in EFS in all patients. CONCLUSIONS: The
      pretreatment ADCmean value of the tumor was an independent prognostic factor for
      EFS in International Federation of Gynecology and Obstetrics stage Ib to III SCC
      of the uterine cervix.

PMID- 25853386
TI  - VO2max Measured with a Self-selected Work Rate Protocol on an Automated
      Treadmill.
AB  - PURPOSE: The use of graded maximal exercise tests for measuring maximal oxygen
      consumption (VO2max) is common practice in both cardiopulmonary rehabilitation
      settings and in sports medicine research. Recent alterations of common testing
      protocols to allow for self-selected work rates (SPV) have elicited VO2max values
      similar to or higher than more traditional style protocols (TP). Research is
      lacking in the delivery of the SPV protocol using a treadmill modality. The
      purpose of the study was to examine the validity of an SPV using an automated
      treadmill for measuring cardiorespiratory fitness. METHODS: Thirteen experienced
      endurance runners completed three maximal exercise tests on a treadmill. Oxygen
      consumption was measured using a computerized system and averaged more than 30-s
      time periods. SPV was completed using an automated treadmill that consisted of a
      sonar range finder, microcontroller, and customized computer software. Subject
      deviations from the middle of the treadmill belt resulted in rapid, graded
      increases or decreases in speed. TP was completed on the same treadmill without
      the use of the automated software. A verification phase protocol (VP) was used to
      verify if VO2 was maximal. RESULTS: Peak work rate achieved during SPV was
      significantly greater than that achieved during TP by 1.2 METs; P < 0.05, d =
      0.564. Oxygen consumption was significantly greater in TP (64.9 +/- 8.2
      mL.kg.min) than SPV (63.4 +/- 7.8 mL.kg.min); P < 0.005, d = 0.195. CONCLUSION:
      An automated treadmill allowed for the completion of SPV similar to what has been
      reported for cycling. SPV with an automated treadmill did not provide a higher
      VO2max than TP despite higher work rates.

PMID- 25853387
TI  - Factors that affect willingness to donate blood for the purpose of biospecimen
      research in the Korean American community.
AB  - OBJECTIVE: Biorepositories have been key resources in examining genetically
      linked diseases, particularly cancer. Asian Americans contribute to
      biorepositories at lower rates than other racial groups, but the reasons for this
      are unclear. We hypothesized that attitudes toward biospecimen research mediate
      the relationship between demographic and healthcare access factors, and
      willingness to donate blood for research purposes among individuals of Korean
      heritage. METHODS: Descriptive statistics and bivariate analyses were utilized to
      characterize the sample with respect to demographic, psychosocial, and behavioral
      variables. Structural equation modeling with 5000 re-sample bootstrapping was
      used to assess each component of the proposed simple mediation models. RESULTS:
      Attitudes towards biospecimen research fully mediate associations between age,
      income, number of years lived in the United States, and having a regular
      physician and willingness to donate blood for the purpose of research.
      CONCLUSION: Participants were willing to donate blood for the purpose of research
      despite having neutral feelings towards biospecimen research as a whole.
      Participants reported higher willingness to donate blood for research purposes
      when they were older, had lived in the United States longer, had higher income,
      and had a regular doctor that they visited. Many of the significant relationships
      between demographic and health care access factors, attitudes towards biospecimen
      research, and willingness to donate blood for the purpose of research may be
      explained by the extent of acculturation of the participants in the United
      States.

PMID- 25853388
TI  - Treatment of severe ocular surface disorders with albumin eye drops.
AB  - PURPOSE: Promising healing effects by albumin eye drops (AED) on the corneal
      epithelium have been demonstrated. The aim of this study was to analyze
      retrospectively if AED are an effective treatment for severe ocular surface
      defects and if recurrences can be reduced. METHODS: Seventeen patients with
      persistent epithelial defects (PED) and 30 patients with sterile corneal ulcers
      (CU) were treated either with 5% AED or 0.1% hyaluronan eye drops (HED) 8 times
      daily until complete epithelium closure. Sizes of the corneal defects, length of
      treatment and follow-up period, as well as recurrence rate were evaluated. Follow
      up of PED was carried out for 126 +/- 21 days in the AED group and 142 +/- 39
      days in the HED group. For CU cases, regular follow-up visits were performed for
      117 +/- 15 days in the AED group and 112 +/- 28 days in the HED group. RESULTS:
      Nine patients in PED group were treated for 11 +/- 4 days with AED and the HED
      group (8 patients) was treated for 10 +/- 3 days until corneal epithelium was
      closed, with only one recurrence in the HED group (P = 0.67). Fifteen patients in
      CU group were treated for 18 +/- 6 days with AED and the HED group (15 patients)
      was treated for 21 +/- 7 days until epithelial closure, with 1 recurrence in the
      AED group and 8 in the HED group (P = 0.03). CONCLUSION: This comparative
      retrospective case-control study showed that AED are able to close corneal
      epithelial defects like CU and PED as good as HED. Even though times of healing
      were similar for both treatments, AED seem to reduce the recurrence of sterile
      CU. Our findings suggest that AED might be beneficial in the management of ocular
      surface epithelial damage; however, further larger studies are necessary to
      confirm these results.

PMID- 25853390
TI  - Synthetic cannabinoids pharmacokinetics and detection methods in biological
      matrices.
AB  - Synthetic cannabinoids (SC), originally developed as research tools, are now
      highly abused novel psychoactive substances. We present a comprehensive
      systematic review covering in vivo and in vitro animal and human pharmacokinetics
      and analytical methods for identifying SC and their metabolites in biological
      matrices. Of two main phases of SC research, the first investigated therapeutic
      applications, and the second abuse-related issues. Administration studies showed
      high lipophilicity and distribution into brain and fat tissue. Metabolite
      profiling studies, mostly with human liver microsomes and human hepatocytes,
      structurally elucidated metabolites and identified suitable SC markers. In
      general, SC underwent hydroxylation at various molecular sites, defluorination of
      fluorinated analogs and phase II metabolites were almost exclusively
      glucuronides. Analytical methods are critical for documenting intake, with
      different strategies applied to adequately address the continuous emergence of
      new compounds. Immunoassays have different cross-reactivities for different SC
      classes, but cannot keep pace with changing analyte targets. Gas chromatography
      and liquid chromatography mass spectrometry assays - first for a few, then
      numerous analytes - are available but constrained by reference standard
      availability, and must be continuously updated and revalidated. In blood and oral
      fluid, parent compounds are frequently present, albeit in low concentrations; for
      urinary detection, metabolites must be identified and interpretation is complex
      due to shared metabolic pathways. A new approach is non-targeted HRMS screening
      that is more flexible and permits retrospective data analysis. We suggest that
      streamlined assessment of new SC's pharmacokinetics and advanced HRMS screening
      provide a promising strategy to maintain relevant assays. 

PMID- 25853389
TI  - Targeting class I histone deacetylase 2 in MYC amplified group 3 medulloblastoma.
AB  - INTRODUCTION: Medulloblastoma (MB) is the most frequent malignant brain tumor in
      children. Four subgroups with distinct genetic, epigenetic and clinical
      characteristics have been identified. Survival remains particularly poor in
      patients with Group 3 tumors harbouring a MYC amplification. We herein explore
      the molecular mechanisms and translational implications of class I histone
      deacetylase (HDAC) inhibition in MYC driven MBs. MATERIAL AND METHODS: Expression
      of HDACs in primary MB subgroups was compared to normal brain tissue. A panel of
      MB cell lines, including Group 3 MYC amplified cell lines, were used as model
      systems. Cells were treated with HDAC inhibitors (HDACi) selectively targeting
      class I or IIa HDACs. Depletion of HDAC2 was performed. Intracellular HDAC
      activity, cellular viability, metabolic activity, caspase activity, cell cycle
      progression, RNA and protein expression were analyzed. RESULTS: HDAC2 was found
      to be overexpressed in MB subgroups with poor prognosis (SHH, Group 3 and Group
      4) compared to normal brain and the WNT subgroup. Inhibition of the enzymatic
      activity of the class I HDACs reduced metabolic activity, cell number, and
      viability in contrast to inhibition of class IIa HDACs. Increased sensitivity to
      HDACi was specifically observed in MYC amplified cells. Depletion of HDAC2
      increased H4 acetylation and induced cell death. Simulation of clinical
      pharmacokinetics showed time-dependent on target activity that correlated with
      binding kinetics of HDACi compounds. CONCLUSIONS: We conclude that HDAC2 is a
      valid drug target in patients with MYC amplified MB. HDACi should cover HDAC2 in
      their inhibitory profile and timing and dosing regimen in clinical trials should
      take binding kinetics of compounds into consideration.

PMID- 25853391
TI  - Phase separation kinetics in amorphous solid dispersions upon exposure to water.
AB  - The purpose of this study was to develop a novel fluorescence technique employing
      environment-sensitive fluorescent probes to study phase separation kinetics in
      hydrated matrices of amorphous solid dispersions (ASDs) following storage at high
      humidity and during dissolution. The initial miscibility of the ASDs was
      confirmed using infrared (IR) spectroscopy and differential scanning calorimetry
      (DSC). Fluorescence spectroscopy, as an independent primary technique, was used
      together with conventional confirmatory techniques including DSC, X-ray
      diffraction (XRD), fluorescence microscopy, and IR spectroscopy to study phase
      separation phenomena. By monitoring the emission characteristics of the
      environment-sensitive fluorescent probes, it was possible to successfully monitor
      amorphous-amorphous phase separation (AAPS) as a function of time in probucol
      poly(vinylpyrrolidone) (PVP) and ritonavir-PVP ASDs after exposure to water. In
      contrast, a ritonavir-hydroxypropylmethylcellulose acetate succinate (HPMCAS)
      ASD, did not show AAPS and was used as a control to demonstrate the capability of
      the newly developed fluorescence method to differentiate systems that showed no
      phase separation following exposure to water versus those that did. The results
      from the fluorescence studies were in good agreement with results obtained using
      various other complementary techniques. Thus, fluorescence spectroscopy can be
      utilized as a fast and efficient tool to detect and monitor the kinetics of phase
      transformations in amorphous solid dispersions during hydration and will help
      provide mechanistic insight into the stability and dissolution behavior of
      amorphous solid dispersions. 

PMID- 25853392
TI  - A coherent approach for analysis of the Illumina HumanMethylation450 BeadChip
      improves data quality and performance in epigenome-wide association studies.
AB  - DNA methylation plays a fundamental role in the regulation of the genome, but the
      optimal strategy for analysis of genome-wide DNA methylation data remains to be
      determined. We developed a comprehensive analysis pipeline for epigenome-wide
      association studies (EWAS) using the Illumina Infinium HumanMethylation450
      BeadChip, based on 2,687 individuals, with 36 samples measured in duplicate. We
      propose new approaches to quality control, data normalisation and batch
      correction through control-probe adjustment and establish a null hypothesis for
      EWAS using permutation testing. Our analysis pipeline outperforms existing
      approaches, enabling accurate identification of methylation quantitative trait
      loci for hypothesis driven follow-up experiments. 

PMID- 25853393
TI  - Outcome of complete intrastromal ring implantation using femtosecond laser in
      pellucid marginal degeneration.
AB  - PURPOSE: To evaluate the effect of complete intrastromal corneal ring
      implantations on patients with pellucid marginal degeneration (PMD). DESIGN:
      Prospective interventional case series. PATIENTS AND METHODS: Thirty-three eyes
      with PMD were included into the study. After pocket creation with femtosecond
      laser (Femtec; 20/10 PerfectVision), MyoRing implantation was performed.
      Uncorrected and corrected distance visual acuity (UDVA, CDVA), subjective
      refraction, keratometry, central corneal thickness, corneal biomechanical profile
      (Ocular Response Analysis), and whole-eye wavefront aberrometry (iTrace) were
      evaluated preoperatively and also postoperatively, 1 month, 3 months, 6 months,
      and 1 year after the operation. RESULTS: One month after surgery, significant
      improvements were observed in UDVA (ANOVA; P=0.02), mean keratometry, sphere
      (ANOVA; P <0.001), and cylinder (ANOVA; P=0.04) with no significant changes
      afterwards. No significant change occurred in the corneal biomechanical profile.
      Primary coma and trefoil reduced after 1 year (ANOVA; P values were 0.02 and
      0.06, respectively). Primary spherical aberration significantly increased
      according to the 1-year follow-up (ANOVA; P<0.001). No significant complication
      was observed. CONCLUSION: MyoRing is considered as a treatment modality for
      spherocylindrical correction in patients with PMD, with an acceptable safety and
      efficacy profile.

PMID- 25853394
TI  - Ethnic variation in rhegmatogenous retinal detachments.
AB  - PURPOSE: We aimed to investigate the clinical variation of rhegmatogenous retinal
      detachments (RD) in patients of different ethnicities. METHODS: Patients
      presenting with a primary RD from two ethnic groups were recruited from our
      tertiary referral hospital between August 2010 and December 2012. Patients who
      self-reported their ethnic origin either as European Caucasian (EC) or South
      Asian (SA) were included. Exclusion criteria included trauma, previous
      vitreoretinal procedures, age under 18 years, complicated cataract surgery and
      the presence of syndromes known to be associated with a high prevalence of RD.
      Detailed phenotypic data were collected. Descriptive and comparative statistical
      analyses were undertaken. RESULTS: 1269 Patients were recruited. 1173 (92.4%)
      were EC. Mean age of onset was 58.3 years (EC) and 54.5 years (SA) (P=0.006).
      75.3% EC and 58.4% SA were phakic (P<0.001). 12.8% of EC and 19.4% of SA patients
      had a lattice retinal degeneration in the affected eye (P=0.003). Refractive
      myopia was greater in SA patients (mean: -6.1DS) than EC (-4.2DS) (P=0.032).
      Additionally, SA patients had a greater mean axial length (25.65 mm) than EC
      (25.06 mm) (P=0.014). No differences were demonstrated in laterality, family
      history, type of retinal break or macular status. CONCLUSIONS: SA patients
      present with RD at an earlier age and have a more severe phenotype than ECs.
      Future management strategies for RD may need to reflect these differences.

PMID- 25853395
TI  - Results of conservative management for consecutive esotropia after intermittent
      exotropia surgery.
AB  - PURPOSE: To examine the clinical course of consecutive esotropia (ET) using
      conservative management, after intermittent exotropia (IXT) surgery. METHODS:
      This study included 149 out of 151 consecutive patients with ET after IXT
      surgery, who were managed conservatively. The clinical course of consecutive ET
      was examined and the patients were classified into two groups based on the
      duration of esodeviation: (1) >3 weeks (persistent ET group, n=56) and (2) <3
      weeks (transient ET group, n=93). Patient characteristics and treatment outcomes,
      including the recurrence of exotropia and stereopsis, were compared between the
      two groups. RESULTS: All patients with ET were managed with full-time alternate
      occlusion and/or with a Fresnel prism. In 149 patients out of 151 consecutive
      patients, 82% of ET disappeared at 12-month follow-up and all at the last follow
      up visit (31.4+/-23.5 months). At the final visit, a recurrence of exotropia of
      >10 prism dioptres was significantly less frequent in the persistent ET group
      than in the transient ET group (25% vs 62%, respectively; P=0.01). However,
      stereopsis outcome was not significantly different between the two groups, and
      stereopsis change was not affected by age. CONCLUSIONS: By using conservative
      management only, persistent consecutive ET after IXT surgery disappeared in most
      cases by the 1-year follow-up visit after surgery. Recurrence of exotropia was
      significantly less frequent in patients with persistent ET, yet the sensory
      outcome was not affected by the duration of consecutive ET or age.

PMID- 25853396
TI  - Evaluation of choroidal thickness using enhanced depth imaging by spectral-domain
      optical coherence tomography in patients with pseudoexfoliation syndrome.
AB  - PURPOSE: To investigate the choroidal thickness using optical coherence
      tomography in the eyes of patients with unilateral and bilateral
      pseudoexfoliation syndrome and to compare them with healthy controls. METHODS: We
      studied four groups: (1) affected eyes from 30 patients with unilateral PEX
      syndrome affecting the right eye of 17 patients and the left eye of 13 patients;
      (2) clinically unaffected eyes of 30 patients with unilateral PEX syndrome; (3)
      the eyes of 30 patients with bilateral PEX syndrome; and (4) the eyes of 30
      normal healthy subjects. Choroidal thickness was evaluated using high-speed, high
      resolution enhanced depth imaging by spectral-domain optical coherence
      tomography. Optical coherence tomography features were compared in all groups
      using the statistical package SPSS v 15.0. RESULTS: The mean subfoveal choroidal
      thicknesses were 237.35+/-58.01 MUm in group 1; 330.75+/-47.84 MUm in group 2;
      206.3+/-86.75 MUm in group 3; and 311.8+/-51.42 MUm in group 4. Significant
      differences in the mean subfoveal choroidal thickness were found between groups 1
      and 2 (P<0.001), groups 1 and 4 (P=0.004), groups 2 and 3 (P<0.001), and groups 3
      and 4 (P<0.001). CONCLUSION: In this study, it was observed that clinically
      affected eyes of patients with PEX syndrome have significantly thinner choroids
      compared with the clinically unaffected eyes of patients with unilateral PEX
      syndrome and eyes of healthy controls.

PMID- 25853397
TI  - Vitiligo iridis and glaucoma: a rare sequelae of small pox.
AB  - PURPOSE: Vitiligo iridis refers to focal areas of iris atrophy as sequelae of
      small pox infection. We report a series of patients with unilateral vitiligo
      iridis, some of whom presented with secondary open-angle glaucoma. METHODS: Three
      patients with vitiligo iridis underwent a comprehensive ophthalmic examination
      including intraocular pressure (IOP) measurement, slit lamp biomicroscopy,
      gonioscopy, and fundus evaluation. Patients' facial features were also documented
      and photographed. RESULTS: All patients were in their sixth decade. Two out the
      three had elevated IOP (52 mm Hg and 36 mm Hg) in the same eye as vitiligo
      iridis, at initial presentation. Gonioscopy showed patchy iris hyperpigmentation
      and fundus evaluation showed glaucomatous optic disc changes in the involved eye.
      One patient responded favourably to topical antiglaucoma medications, whereas the
      other was taken up for combined phacoemulsification-trabeculectomy with good
      results. The third patient had normal IOP in the involved eye. All three patients
      gave a history of small pox in childhood and had pitted facial scars typical of
      previous small pox infection. CONCLUSIONS: Vitiligo iridis may be associated with
      the secondary glaucoma as a long-term sequelae of small pox. It may be prudent to
      periodically follow-up such patients for development of raised IOP in the future.

PMID- 25853398
TI  - Where is the junction of zone 2 and zone 3 temporal retina in RetCam images of
      acute retinopathy of prematurity?

PMID- 25853399
TI  - Storage stability of bevacizumab in polycarbonate and polypropylene syringes.
AB  - PURPOSE: To compare and examine the storage stability of compounded bevacizumab
      in polycarbonate (PC) and polypropylene (PP) syringes over a 6-month period. PC
      syringes have been used in a recent clinical study and bevacizumab stability has
      not been reported for this type of syringe. METHODS: Repackaged bevacizumab was
      obtained from Moorfields Pharmaceuticals in PC and PP syringes. Bevacizumab from
      the stored syringes was analysed at monthly time points for a 6-month period and
      compared with bevacizumab from a freshly opened vial at each time point. SDS-PAGE
      electrophoresis and size-exclusion chromatography (SEC) was used to observe
      aggregation and degradation. Dynamic light scattering (DLS) provided information
      about the hydrodynamic size and particle size distribution of bevacizumab in
      solution. VEGF binding and the active concentration of bevacizumab was determined
      by surface plasmon resonance (SPR) using Biacore. RESULTS: SDS-PAGE and SEC
      analysis did not show any changes in the presence of higher molecular weight
      species (HMWS) or degradation products in PC and PP syringes from T0 to T6
      compared with bevacizumab sampled from a freshly opened vial. The hydrodynamic
      diameter of bevacizumab in the PC syringe after 6 months of storage was not
      significantly different to bevacizumab taken from a freshly opened vial. Using
      SPR, the VEGF binding activity of bevacizumab in the PC syringe was comparable to
      bevacizumab taken from a freshly opened vial. CONCLUSION: No significant
      difference over a 6-month period was observed in the quality of bevacizumab
      repackaged into prefilled polycarbonate and polypropylene syringes when compared
      with bevacizumab that is supplied from the vial.

PMID- 25853400
TI  - Evaluation of the retinal nerve fibre layer and ganglion cell complex thickness
      in pituitary macroadenomas without optic chiasmal compression.
AB  - PURPOSE: The aim of this prospective study was to measure the thickness of the
      circumpapillary retinal nerve fibre layer (cpRNFL) and the ganglion cell complex
      (GCC) using spectral domain optical coherence tomography (SD-OCT) in a cohort of
      consecutive de novo patients with pituitary macroadenomas without chiasmal
      compression. PATIENTS AND METHODS: Twenty-two consecutive patients with pituitary
      macroadenoma without chiasmal compression (16 men, 6 women, aged 45.2+/-14.6
      years, 43 eyes) entered the study between September 2011 and June 2013. Among
      them, 31.8% harboured a growth hormone-secreting pituitary adenoma, 27.3% a
      prolactin-secreting pituitary adenoma, 27.3% a corticotrophin-secreting pituitary
      adenoma, and 13.6% a non-secreting pituitary tumour. Eighteen subjects (nine
      females, nine males, mean age 36.47+/-6.37 years; 33 eyes) without pituitary
      adenoma, with normal ophthalmic examination, served as controls. In both patients
      and controls, cpRNFL and GCC thicknesses were measured by SD-OCT. RESULTS:
      Patients were significantly older (P=0.02) than controls. Best corrected visual
      acuity, intraocular pressure, colour fundus photography, and automatic perimetry
      test were within the normal range in patients and controls. Conversely, cpRNFL
      (P=0.009) and GCC (P<0.0001) were significantly thinner in patients than in
      controls. The average GCC (r=0.306, P=0.046) significantly correlated with the
      presence of arterial hypertension. OCT parameters did not differ significantly
      between patients with a tumour volume above the median and those with a tumour
      volume below the median. CONCLUSION: Pituitary macroadenomas, even in the absence
      of chiasmal compression, may induce GCC and retinal nerve fibre layer thinning.
      SD-OCT may have a role in the early diagnosis and management of patients with
      pituitary tumours.

PMID- 25853401
TI  - The role of computerised tomography in predicting visual outcome in ocular trauma
      patients.
AB  - PURPOSE: Ocular blast injuries in the military setting are particularly
      associated with significant maxillofacial trauma and/or brain injury. The
      opportunity to perform a comprehensive ophthalmic evaluation is frequently
      limited in the acute multiple trauma scenario. We aim to describe the
      relationship between the clinical effects of acute ocular and orbital blast
      trauma with the findings on computerised tomography (CT). METHODS: This was a
      retrospective consecutive case series of all soldiers with facial and/or
      suspected ocular injuries. A total of 80 eyes that had suffered blast injuries of
      varying severity were studied. Assessment of orbital and ocular CT images were
      performed by military consultant radiologists. A comparison was made with actual
      clinical findings. Statistical analysis was performed using Fisher's exact test.
      RESULTS: No pathological findings were described in 37 of the 80 eyes imaged by
      orbital and ocular CT scans. Clinically, these eyes and orbits were all found to
      be intact, or had minor trauma. All foreign bodies and penetrating eye injuries
      were successfully diagnosed by CT. Absence of an orbital fracture did not rule
      out a globe injury. However, a corneal or scleral defect was less likely when an
      orbital fracture was absent. CONCLUSION: The eye is a delicate structure prone to
      injury that requires urgent repair if breached. It is difficult to assess
      thoroughly in the unconscious or distressed patient. In this context, CT imaging
      is invaluable to be able to make a relatively confident prediction of clinical
      findings and decide upon the necessity for acute ophthalmic surgical
      intervention.

PMID- 25853403
TI  - Recrossing and Tunneling in the Kinetics Study of the OH + CH4 -> H2O + CH3
      Reaction.
AB  - Thermal rate constants and several kinetic isotope effects were evaluated for the
      OH + CH4 hydrogen abstraction reaction using two kinetics approaches, ring
      polymer molecular dynamics (RPMD) and variational transition state theory with
      multidimensional tunneling (VTST/MT), based on a refined full-dimensional
      analytical potential energy surface, PES-2014, in the temperature range 200-2000
      K. For the OH + CH4 reaction, at low temperatures, T = 200 K, where the quantum
      tunneling effect is more important, RPMD overestimates the experimental rate
      constants due to problems associated with PES-2014 in the deep tunneling regime
      and to the known overestimation of this method in asymmetric reactions, while
      VTST/MT presents a better agreement, differences about 10%, due to compensation
      of several factors, inaccuracy of PES-2014, and ignoring anharmonicity. In the
      opposite extreme, T = 1000 K, recrossing effects play the main role, and the
      difference between both methods is now smaller, by a factor of 1.5. Given that
      RPMD results are exact in the high-temperature limit, the discrepancy is due to
      the approaches used in the VTST/MT method, such as ignoring the anharmonicity of
      the lowest vibrational frequencies along the reaction path, which leads to an
      incorrect location of the dividing surface between reactants and products. The
      analysis of several kinetic isotope effects, OH + CD4, OD + CH4, and OH +
      (12)CH4/(13)CH4, sheds light on these problems and confirms the previous
      conclusions. In general, the agreement with the available experimental data is
      reasonable, although discrepancies persist, and they have been analyzed as a
      function of the many factors affecting the theoretical calculations: limitations
      of the kinetics methods and of the potential energy surface, and uncertainties in
      the experimental measurements. Finally, in the absence of full-dimensional
      quantum mechanics calculations, this study represents an additional step in
      understanding this seven-atom hydrogen abstraction reaction. 

PMID- 25853402
TI  - Focal choroidal excavation in patients with central serous chorioretinopathy.
AB  - PURPOSE: To evaluate the prevalence and clinical features of focal choroidal
      excavation (FCE) in patients presenting with central serous chorioretinopathy
      (CSC). METHODS: This is a retrospective consecutive case series of consecutive
      patients with CSC who were referred for spectral domain optical coherence
      tomography (SD-OCT) between January 2010 and December 2011. Medical records were
      reviewed and clinical features including presence of FCE in SD-OCT, fluorescence
      angiography (FA), and indocyanine green angiography (ICGA) were studied. RESULTS:
      Among the 116 CSC patients assessed, FCE was found in 11 eyes of 7 (6.0%)
      patients. FCE was associated with subretinal fluid in six eyes of six patients
      and serous pigment epithelial detachment in three eyes of two patients. The mean
      central subfield retinal thickness of CSC eyes with FCE was 283.7 MUm, compared
      with 377.5 MUm for CSC eyes without FCE (Mann-Whitney U-test, P=0.020). Five FCE
      eyes of five patients had focal leakage on FA. Choroidal hyperpermeability on
      ICGA was found in seven CSC eyes with FCE, with four eyes showing hypofluorescent
      spot corresponding to the FCE. After a mean follow-up of 16 months, visual acuity
      of all 11 eyes with FCE remained stable or improved at the last follow-up.
      CONCLUSION: FCE is not an uncommon feature in patients with CSC and might be
      associated with choroidal hemodynamic disturbances.

PMID- 25853405
TI  - Hysteresis analysis and positioning control for a magnetic shape memory actuator.
AB  - Magnetic shape memory alloys (MSM alloys), a new kind of smart materials, have
      become a potential candidate in many engineering fields. MSMs have the advantage
      of bearing a huge strain, much larger than other materials. In addition, they
      also have fast response. These characteristics make MSM a good choice in micro
      engineering. However, MSMs display the obvious hysteresis phenomenon of nonlinear
      behavior. Thus the difficulty in using the MSM element as a positioning actuator
      is increased due to the hysteresis. In this paper, the hysteresis phenomenon of
      the MSM actuator is analyzed, and the closed-loop positioning control is also
      implemented experimentally. For that, a modified fuzzy sliding mode control
      (MFSMC) is proposed. The MFSMC and the PID control are used to design the
      controllers for realizing the positioning control. The experimental results are
      compared under different experimental conditions, such as different frequency,
      amplitude, and loading. The experimental results show that the precise
      positioning control of MFSMC can be achieved satisfactorily. 

PMID- 25853404
TI  - Experimental and numerical characterization of a hybrid Fabry-Perot cavity for
      temperature sensing.
AB  - A hybrid Fabry-Perot cavity sensing head based on a four-bridge microstructured
      fiber is characterized for temperature sensing. The characterization of this
      cavity is performed numerically and experimentally in the L-band. The sensing
      head output signal presents a linear variation with temperature changes, showing
      a sensitivity of 12.5 pm/ degrees C. Moreover, this Fabry-Perot cavity exhibits
      good sensitivity to polarization changes and high stability over time. 

PMID- 25853406
TI  - Nonlinear optimization-based device-free localization with outlier link
      rejection.
AB  - Device-free localization (DFL) is an emerging wireless technique for estimating
      the location of target that does not have any attached electronic device. It has
      found extensive use in Smart City applications such as healthcare at home and
      hospitals, location-based services at smart spaces, city emergency response and
      infrastructure security. In DFL, wireless devices are used as sensors that can
      sense the target by transmitting and receiving wireless signals collaboratively.
      Many DFL systems are implemented based on received signal strength (RSS)
      measurements and the location of the target is estimated by detecting the changes
      of the RSS measurements of the wireless links. Due to the uncertainty of the
      wireless channel, certain links may be seriously polluted and result in erroneous
      detection. In this paper, we propose a novel nonlinear optimization approach with
      outlier link rejection (NOOLR) for RSS-based DFL. It consists of three key
      strategies, including: (1) affected link identification by differential RSS
      detection; (2) outlier link rejection via geometrical positional relationship
      among links; (3) target location estimation by formulating and solving a
      nonlinear optimization problem. Experimental results demonstrate that NOOLR is
      robust to the fluctuation of the wireless signals with superior localization
      accuracy compared with the existing Radio Tomographic Imaging (RTI) approach. 

PMID- 25853407
TI  - Detection of steel fatigue cracks with strain sensing sheets based on large area
      electronics.
AB  - Reliable early-stage damage detection requires continuous monitoring over large
      areas of structure, and with sensors of high spatial resolution. Technologies
      based on Large Area Electronics (LAE) can enable direct sensing and can be scaled
      to the level required for Structural Health Monitoring (SHM) of civil structures
      and infrastructure. Sensing sheets based on LAE contain dense arrangements of
      thin-film strain sensors, associated electronics and various control circuits
      deposited and integrated on a flexible polyimide substrate that can cover large
      areas of structures. This paper presents the development stage of a prototype
      strain sensing sheet based on LAE for crack detection and localization. Two types
      of sensing-sheet arrangements with size 6 * 6 inch (152 * 152 mm) were designed
      and manufactured, one with a very dense arrangement of sensors and the other with
      a less dense arrangement of sensors. The sensing sheets were bonded to steel
      plates, which had a notch on the boundary, so the fatigue cracks could be
      generated under cyclic loading. The sensors within the sensing sheet that were
      close to the notch tip successfully detected the initialization of fatigue crack
      and localized the damage on the plate. The sensors that were away from the crack
      successfully detected the propagation of fatigue cracks based on the time history
      of the measured strain. The results of the tests have validated the general
      principles of the proposed sensing sheets for crack detection and identified
      advantages and challenges of the two tested designs. 

PMID- 25853408
TI  - Sensing properties of Pd-loaded Co3O4 film for a ppb-level NO gas sensor.
AB  - We prepared 0.1 wt%-30 wt% Pd-loaded Co3O4 by a colloidal mixing method and
      investigated the sensing properties of a Pd-loaded Co3O4 sensor element, such as
      the sensor response, 90% response time, 90% recovery time, and signal-to-noise
      (S/N) ratio, toward low nitric oxide (NO) gas levels in the range from 50 to 200
      parts per billion. The structural properties of the Pd-loaded Co3O4 powder were
      investigated using X-ray diffraction analysis and transmission electron
      microscopy. Pd in the powder existed as PdO. The sensor elements with 0.1 wt%-10
      wt% Pd content have higher sensor properties than those without any Pd content.
      The response of the sensor element with a 30 wt% Pd content decreased markedly
      because of the aggregation and poor dispersibility of the PdO particles. High
      sensor response and S/N ratio toward the NO gas were achieved when a sensor
      element with 10 wt% Pd content was used. 

PMID- 25853409
TI  - The ethical importance of safety.

PMID- 25853410
TI  - Cobalt(II) coordination polymer exhibiting single-ion-magnet-type field-induced
      slow relaxation behavior.
AB  - A one-dimensional cobalt(II) coordination polymer, [Co(btm)2(SCN)2.H2O]n [btm =
      bis(1H-1,2,4-triazol-1-yl)methane], was synthesized and magnetically
      characterized. The isolated slightly distorted octahedral Co(II) ion displays
      field-induced slow relaxation with a big positive axial and a negative rhombic
      magnetic anisotropy (D = 93.9 cm(-1) and E = -10.5 cm(-1)), and the anisotropy
      energy barrier is 45.4 K. 

PMID- 25853411
TI  - Sequential push-pull pumping mechanism for washing and evacuation of an
      immunoassay reaction chamber on a microfluidic CD platform.
AB  - A centrifugal compact disc (CD) microfluidic platform with reservoirs, micro
      channels, and valves can be employed for implementing a complete immunoassay.
      Detection or biosensor chambers are either coated for immuno-interaction or a
      biosensor chip is inserted in them. On microfluidic CDs featuring such multi-step
      chemical/biological processes, the biosensor chamber must be repeatedly filled
      with fluids such as enzymes solutions, buffers, and washing solutions. After each
      filling step, the biosensor chamber needs to be evacuated by a passive siphoning
      process to prepare it for the next step in the assay. However, rotational speed
      dependency and limited space on a CD are two big obstacles to performing such
      repetitive filling and siphoning steps. In this work, a unique thermo-pneumatic
      (TP) Push-Pull pumping method is employed to provide a superior alternative
      biosensor chamber filling and evacuation technique. The proposed technique is
      demonstrated on two CD designs. The first design features a simple two-step
      microfluidic process to demonstrate the evacuation technique, while the second
      design shows the filling and evacuation technique with an example sequence for an
      actual immunoassay. In addition, the performance of the filling and evacuation
      technique as a washing step is also evaluated quantitatively and compared to the
      conventional manual bench top washing method. The two designs and the performance
      evaluation demonstrate that the technique is simple to implement, reliable, easy
      to control, and allows for repeated push-pulls and thus filling and emptying of
      the biosensor chamber. Furthermore, by addressing the issue of rotational speed
      dependency and limited space concerns in implementing repetitive filling and
      evacuation steps, this newly introduced technique increases the flexibility of
      the microfluidic CD platform to perform multi-step biological and chemical
      processes. 

PMID- 25853413
TI  - The evolutionary origins of the southern ocean Philobryid bivalves: hidden
      biodiversity, ancient persistence.
AB  - Philobryids (Bivalvia: Arcoida) are one of the most speciose marine bivalve
      families in the Southern Ocean and are common throughout the Southern Hemisphere.
      Considering this diversity and their brooding reproductive mode (limiting long
      distance dispersal), this family may have been present in the Southern Ocean
      since its inception. However Philobrya and Adacnarca appear only in the
      Quaternary fossil record of the Antarctic, suggesting a much more recent
      incursion. Molecular dating provides an independent means of measuring the time
      of origin and radiation of this poorly known group. Here we present the first
      combined molecular and morphological investigation of the Philobryidae in the
      Southern Ocean. Two nuclear loci (18S and 28S) were amplified from 35 Southern
      Ocean Adacnarca and Philobrya specimens, with a combined sequence length of 2,282
      base pairs (bp). Adacnarca specimens (A. nitens and A. limopsoides) were resolved
      as a strongly supported monophyletic group. Genus Philobrya fell into two
      strongly supported groups ('sublaevis' and 'magellanica/wandelensis'),
      paraphyletic with Adacnarca. The A. nitens species complex is identified as at
      least seven morpho-species through morphological and genetic analysis of taxon
      clustering. Phylogenetic analyses resolve Philobryidae as a strongly supported
      monophyletic clade and sister taxon to the Limopsidae, as anticipated by their
      classification into the superfamily Limopsoidea. Bayesian relaxed clock analyses
      of divergence times suggest that genus Adacnarca radiated in the Southern Ocean
      from the Early Paleogene, while P. sublaevis and P. wandelensis clades radiated
      in the late Miocene, following the formation of the Antarctic Circumpolar
      Current. 

PMID- 25853412
TI  - Phylogenetic molecular species delimitations unravel potential new species in the
      pest genus Spodoptera Guenee, 1852 (Lepidoptera, Noctuidae).
AB  - Nowadays molecular species delimitation methods promote the identification of
      species boundaries within complex taxonomic groups by adopting innovative species
      concepts and theories (e.g. branching patterns, coalescence). As some of them can
      efficiently deal with large single-locus datasets, they could speed up the
      process of species discovery compared to more time consuming molecular methods,
      and benefit from the existence of large public datasets; these methods can also
      particularly favour scientific research and actions dealing with threatened or
      economically important taxa. In this study we aim to investigate and clarify the
      status of economically important moths species belonging to the genus Spodoptera
      (Lepidoptera, Noctuidae), a complex group in which previous phylogenetic analyses
      and integrative approaches already suggested the possible occurrence of cryptic
      species and taxonomic ambiguities. In this work, the effectiveness of innovative
      (and faster) species delimitation approaches to infer putative species boundaries
      has been successfully tested in Spodoptera, by processing the most comprehensive
      dataset (in terms of number of species and specimens) ever achieved; results are
      congruent and reliable, irrespective of the set of parameters and phylogenetic
      models applied. Our analyses confirm the existence of three potential new species
      clusters (for S. exigua (Hubner, 1808), S. frugiperda (J.E. Smith, 1797) and S.
      mauritia (Boisduval, 1833)) and support the synonymy of S. marima (Schaus, 1904)
      with S. ornithogalli (Guenee, 1852). They also highlight the ambiguity of the
      status of S. cosmiodes (Walker, 1858) and S. descoinsi Lalanne-Cassou & Silvain,
      1994. This case study highlights the interest of molecular species delimitation
      methods as valuable tools for species discovery and to emphasize taxonomic
      ambiguities. 

PMID- 25853414
TI  - Correction: prevalence and risk factors of anaemia among children aged between 6
      months and 14 years in Kenya.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0113756.]. 

PMID- 25853416
TI  - Back to the roots: the integration of a constructed wetland into a recirculating
      hatchery - a case study.
AB  - Aquaculture is currently one of the fastest growing food-producing sectors,
      accounting for around 50% of the world's food fish. Limited resources, together
      with climatic change, have stimulated the search for solutions to support and
      sustain the production of fish as a nutritious food. The integration of a
      constructed wetland (CW) into a recirculating hatchery (RHS) was evaluated with
      respect to its economic feasibility and environmental impact. The outcome of
      eight production cycles showed the potential of CW integration for expanded
      production without increased operation costs or environmental load. Concretely,
      the use of constructed wetland allows the rearing about 40% more fish biomass,
      resulting in higher production and profitability. The low requirements for space,
      fresh water, and energy enable the establishment of such systems almost anywhere.
      Constructed wetlands could enhance the productivity of existing small scale
      facilities, as well as larger systems, to address economic and environmental
      issues in aquaculture. Such systems have potential to be sustainable in the
      context of possible future climate change and resource limitations. 

PMID- 25853417
TI  - Alternating antibiotics render resistant bacteria beatable.

PMID- 25853415
TI  - Domain-swapped dimer of Pseudomonas aeruginosa cytochrome c551: structural
      insights into domain swapping of cytochrome c family proteins.
AB  - Cytochrome c (cyt c) family proteins, such as horse cyt c, Pseudomonas aeruginosa
      cytochrome c551 (PA cyt c551), and Hydrogenobacter thermophilus cytochrome c552
      (HT cyt c552), have been used as model proteins to study the relationship between
      the protein structure and folding process. We have shown in the past that horse
      cyt c forms oligomers by domain swapping its C-terminal helix, perturbing the Met
      heme coordination significantly compared to the monomer. HT cyt c552 forms dimers
      by domain swapping the region containing the N-terminal alpha-helix and heme,
      where the heme axial His and Met ligands belong to different protomers. Herein,
      we show that PA cyt c551 also forms domain-swapped dimers by swapping the region
      containing the N-terminal alpha-helix and heme. The secondary structures of the
      M61A mutant of PA cyt c551 were perturbed slightly and its oligomer formation
      ability decreased compared to that of the wild-type protein, showing that the
      stability of the protein secondary structures is important for domain swapping.
      The hinge loop of domain swapping for cyt c family proteins corresponded to the
      unstable region specified by hydrogen exchange NMR measurements for the monomer,
      although the swapping region differed among proteins. These results show that the
      unstable loop region has a tendency to become a hinge loop in domain-swapped
      proteins. 

PMID- 25853418
TI  - Reduced adolescent-age spatial learning ability associated with elevated juvenile
      age superoxide levels in complex I mouse mutants.
AB  - Large-scale, heteroplasmic and generally pathogenic mtDNA defects (as induced by
      defective mitochondrial DNA polymerase, clonal mutations or DNA deletions) are
      known to negatively impact on life span and can result in apoptosis and tissue
      loss in, e.g., skeletal muscle or reduce learning abilities. The functional
      impact of homoplasmic specific mtDNA point mutations, e.g., in genes coding for
      the electron transport chain, however, remains a matter of debate. The present
      study contributes to this discussion and provides evidence that a single point
      mutation in complex I of the respiratory chain is associated with impairment of
      spatial navigation in adolescent (6-month-old) mice, i.e., reduced performance in
      the Morris Water Maze, which goes along with increased production of reactive
      oxygen species (ROS) in juvenile mice (3 months) but not at the age of phenotype
      expression. A point mutation in complex III goes along with only a mild and non
      significant negative effect on cognitive performance and no significant changes
      in ROS production. These findings suggest to also consider the ontogenetic
      development of phenotypes when studying mtDNA mutations and highlights a possible
      impact of complex I dysfunction on the emergence of neurological deficits. 

PMID- 25853420
TI  - Analysis of the Causes of Failed Antireflux Surgery and the Principles of
      Treatment: A Review.
AB  - IMPORTANCE: Although the diagnostic evaluation and technical elements for a
      successful laparoscopic fundoplication have been clearly identified, 10% to 20%
      of patients will eventually experience recurrence of their symptoms. The
      management of patients who fail antireflux surgery is complex and not well
      codified. OBJECTIVE: To provide an evidence- and experience-based analysis of the
      causes of failed antireflux surgery and to underscore the principles of
      treatment. EVIDENCE REVIEW: PubMed was searched for articles published between
      1980 and 2014. The search terms included were the following: heartburn,
      regurgitation, dysphagia, gastroesophageal reflux disease, cough, aspiration,
      laryngitis, GERD, GORD, endoscopy, manometry, pH monitoring, proton pump
      inhibitors, and Nissen fundoplication. FINDINGS: Before planning therapy, a
      careful workup is necessary to determine whether the symptoms are due to
      recurrent reflux and to understand what caused the recurrence. Subsequently,
      therapy needs to be individualized based on the symptoms and on the findings of
      the workup. In some patients, a nonesophageal cause will be identified. Among
      patients with recurrent reflux, some will do well with acid-reducing medications
      and others will need another operation. CONCLUSIONS AND RELEVANCE: Laparoscopic
      antireflux surgery is a very effective and long-lasting treatment for
      gastroesophageal reflux disease. Its success is based on a careful preoperative
      evaluation and on the performance of a fundoplication that respects the key
      technical elements. Patients who are still symptomatic postoperatively must be
      thoroughly evaluated to identify the cause of failure, and treatment must be
      individualized.

PMID- 25853419
TI  - Modulation of sweet taste by umami compounds via sweet taste receptor subunit
      hT1R2.
AB  - Although the five basic taste qualities-sweet, sour, bitter, salty and umami-can
      be recognized by the respective gustatory system, interactions between these
      taste qualities are often experienced when food is consumed. Specifically, the
      umami taste has been investigated in terms of whether it enhances or reduces the
      other taste modalities. These studies, however, are based on individual
      perception and not on a molecular level. In this study we investigated umami
      sweet taste interactions using umami compounds including monosodium glutamate
      (MSG), 5'-mononucleotides and glutamyl-dipeptides, glutamate-glutamate (Glu-Glu)
      and glutamate-aspartic acid (Glu-Asp), in human sweet taste receptor hT1R2/hT1R3
      expressing cells. The sensitivity of sucrose to hT1R2/hT1R3 was significantly
      attenuated by MSG and umami active peptides but not by umami active nucleotides.
      Inhibition of sweet receptor activation by MSG and glutamyl peptides is obvious
      when sweet receptors are activated by sweeteners that target the extracellular
      domain (ECD) of T1R2, such as sucrose and acesulfame K, but not by cyclamate,
      which interact with the T1R3 transmembrane domain (TMD). Application of umami
      compounds with lactisole, inhibitory drugs that target T1R3, exerted a more
      severe inhibitory effect. The inhibition was also observed with F778A sweet
      receptor mutant, which have the defect in function of T1R3 TMD. These results
      suggest that umami peptides affect sweet taste receptors and this interaction
      prevents sweet receptor agonists from binding to the T1R2 ECD in an allosteric
      manner, not to the T1R3. This is the first report to define the interaction
      between umami and sweet taste receptors. 

PMID- 25853421
TI  - EBNA2 binds to genomic intervals associated with multiple sclerosis and overlaps
      with vitamin D receptor occupancy.
AB  - Epstein-Barr virus (EBV) is a non-heritable factor that associates with multiple
      sclerosis (MS). However its causal relationship with the disease is still
      unclear. The virus establishes a complex co-existence with the host that includes
      regulatory influences on gene expression. Hence, if EBV contributes to the
      pathogenesis of MS it may do so by interacting with disease predisposing genes.
      To verify this hypothesis we evaluated EBV nuclear antigen 2 (EBNA2, a protein
      that recent works by our and other groups have implicated in disease development)
      binding inside MS associated genomic intervals. We found that EBNA2 binding
      occurs within MS susceptibility sites more than expected by chance (factor of
      observed vs expected overlap [O/E] = 5.392-fold, p < 2.0e-05). This remains
      significant after controlling for multiple genomic confounders. We then asked
      whether this observation is significant per se or should also be viewed in the
      context of other disease relevant gene-environment interactions, such as those
      attributable to vitamin D. We therefore verified the overlap between EBNA2
      genomic occupancy and vitamin D receptor (VDR) binding sites. EBNA2 shows a
      striking overlap with VDR binding sites (O/E = 96.16-fold, p < 2.0e-05), even
      after controlling for the chromatin accessibility state of shared regions (p
      <0.001). Furthermore, MS susceptibility regions are preferentially targeted by
      both EBNA2 and VDR than by EBNA2 alone (enrichment difference = 1.722-fold, p =
      0.0267). Taken together, these findings demonstrate that EBV participates in the
      gene-environment interactions that predispose to MS. 

PMID- 25853422
TI  - Clinical evaluation of a loop-mediated isothermal amplification (LAMP) assay for
      rapid detection of Neisseria meningitidis in cerebrospinal fluid.
AB  - BACKGROUND: Neisseria meningitidis (Nm) is a leading causative agent of bacterial
      meningitis in humans. Traditionally, meningococcal meningitis has been diagnosed
      by bacterial culture. However, isolation of bacteria from patients' cerebrospinal
      fluid (CSF) is time consuming and sometimes yields negative results. Recently,
      polymerase chain reaction (PCR)-based diagnostic methods of detecting Nm have
      been considered the gold standard because of their superior sensitivity and
      specificity compared with culture. In this study, we developed a loop-mediated
      isothermal amplification (LAMP) method and evaluated its ability to detect Nm in
      cerebrospinal fluid (CSF). METHODOLOGY/PRINCIPAL FINDINGS: We developed a
      meningococcal LAMP assay (Nm LAMP) that targets the ctrA gene. The primer
      specificity was validated using 16 strains of N. meningitidis (serogroup A, B, C,
      D, 29-E, W-135, X, Y, and Z) and 19 non-N. meningitidis species. Within 60 min,
      the Nm LAMP detected down to ten copies per reaction with sensitivity 1000-fold
      more than that of conventional PCR. The LAMP assays were evaluated using a set of
      1574 randomly selected CSF specimens from children with suspected meningitis
      collected between 1998 and 2002 in Vietnam, China, and Korea. The LAMP method was
      shown to be more sensitive than PCR methods for CSF samples (31 CSF samples were
      positive by LAMP vs. 25 by PCR). The detection rate of the LAMP method was
      substantially higher than that of the PCR method. In a comparative analysis of
      the PCR and LAMP assays, the clinical sensitivity, specificity, positive
      predictive value, and negative predictive value of the LAMP assay were 100%,
      99.6%, 80.6%, and 100%, respectively. CONCLUSIONS/SIGNIFICANCE: Compared to PCR,
      LAMP detected Nm with higher analytical and clinical sensitivity. This sensitive
      and specific LAMP method offers significant advantages for screening patients on
      a population basis and for diagnosis in clinical settings.

PMID- 25853423
TI  - Inequalities in maternal health care utilization in sub-Saharan African
      countries: a multiyear and multi-country analysis.
AB  - To assess social inequalities in the use of antenatal care (ANC), facility based
      delivery (FBD), and modern contraception (MC) in two contrasting groups of
      countries in sub-Saharan Africa divided based on their progress towards maternal
      mortality reduction. Six countries were included in this study. Three countries
      (Ethiopia, Madagascar, and Uganda) had <350 MMR in 2010 with >4.5% average annual
      reduction rate while another three (Cameroon, Zambia, and Zimbabwe) had >550 MMR
      in 2010 with only <1.5% average annual reduction rate. All of these countries had
      at least three rounds of Demographic and Health Surveys (DHS) before 2012. We
      measured rate ratios and differences, as well as relative and absolute
      concentration indices in order to examine within-country geographical and wealth
      based inequalities in the utilization of ANC, FBD, and MC. In the countries which
      have made sufficient progress (i.e. Ethiopia, Madagascar, and Uganda), ANC use
      increased by 8.7, 9.3 and 5.7 percent, respectively, while the utilization of FBD
      increased by 4.7, 0.7 and 20.2 percent, respectively, over the last decade. By
      contrast, utilization of these services either plateaued or decreased in
      countries which did not make progress towards reducing maternal mortality, with
      the exception of Cameroon. Utilization of MC increased in all six countries but
      remained very low, with a high of 40.5% in Zimbabwe and low of 16.1% in Cameroon
      as of 2011. In general, relative measures of inequalities were found to have
      declined overtime in countries making progress towards reducing maternal
      mortality. In countries with insufficient progress towards maternal mortality
      reduction, these indicators remained stagnant or increased. Absolute measures for
      geographical and wealth-based inequalities remained high invariably in all six
      countries. The increasing trend in the utilization of maternal care services was
      found to concur with a steady decline in maternal mortality. Relative inequality
      declined overtime in countries which made progress towards reducing maternal
      mortality. 

PMID- 25853424
TI  - Peripheral blood mononuclear cells HIV DNA levels impact intermittently on
      neurocognition.
AB  - OBJECTIVES: To determine the contribution of peripheral blood mononuclear cells'
      (PBMCs) HIV DNA levels to HIV-associated dementia (HAD) and non-demented HIV
      associated neurocognitive disorders (HAND) in chronically HIV-infected adults
      with long-term viral suppression on combined antiretroviral treatment (cART).
      METHODS: Eighty adults with chronic HIV infection on cART (>97% with plasma and
      CSF HIV RNA <50 copies/mL) were enrolled into a prospective observational cohort
      and underwent assessments of neurocognition and pre-morbid cognitive ability at
      two visits 18 months apart. HIV DNA in PBMCs was measured by real-time PCR at the
      same time-points. RESULTS: At baseline, 46% had non-demented HAND; 7.5% had HAD.
      Neurocognitive decline occurred in 14% and was more likely in those with HAD
      (p<.03). Low pre-morbid cognitive ability was uniquely associated with HAD
      (p<.05). Log10 HIV DNA copies were stable between study visits (2.26 vs. 2.22 per
      106 PBMC). Baseline HIV DNA levels were higher in those with lower pre-morbid
      cognitive ability (p<.04), and higher in those with no ART treatment during HIV
      infection 1st year (p = .03). Baseline HIV DNA was not associated with overall
      neurocognition. However, % ln HIV DNA change was associated with decline in
      semantic fluency in unadjusted and adjusted analyses (p = .01-.03), and motor
      coordination (p = .02-.12) to a lesser extent. CONCLUSIONS: PBMC HIV DNA plays a
      role in HAD pathogenesis, and this is moderated by pre-morbid cognitive ability
      in the context of long-term viral suppression. While the HIV DNA levels in PBMC
      are not associated with current non-demented HAND, increasing HIV DNA levels were
      associated with a decline in neurocognitive functions associated with HAND
      progression.

PMID- 25853425
TI  - Correction: a tale of two recent spills-comparison of 2014 Galveston Bay and 2010
      Deepwater Horizon Oil Spill Residues.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0118098.].

PMID- 25853426
TI  - Abundant genetic overlap between blood lipids and immune-mediated diseases
      indicates shared molecular genetic mechanisms.
AB  - Epidemiological studies suggest a relationship between blood lipids and immune
      mediated diseases, but the nature of these associations is not well understood.
      We used genome-wide association studies (GWAS) to investigate shared single
      nucleotide polymorphisms (SNPs) between blood lipids and immune-mediated
      diseases. We analyzed data from GWAS (n~200,000 individuals), applying new False
      Discovery Rate (FDR) methods, to investigate genetic overlap between blood lipid
      levels [triglycerides (TG), low density lipoproteins (LDL), high density
      lipoproteins (HDL)] and a selection of archetypal immune-mediated diseases
      (Crohn's disease, ulcerative colitis, rheumatoid arthritis, type 1 diabetes,
      celiac disease, psoriasis and sarcoidosis). We found significant polygenic
      pleiotropy between the blood lipids and all the investigated immune-mediated
      diseases. We discovered several shared risk loci between the immune-mediated
      diseases and TG (n = 88), LDL (n = 87) and HDL (n = 52). Three-way analyses
      differentiated the pattern of pleiotropy among the immune-mediated diseases. The
      new pleiotropic loci increased the number of functional gene network nodes
      representing blood lipid loci by 40%. Pathway analyses implicated several novel
      shared mechanisms for immune pathogenesis and lipid biology, including
      glycosphingolipid synthesis (e.g. FUT2) and intestinal host-microbe interactions
      (e.g. ATG16L1). We demonstrate a shared genetic basis for blood lipids and immune
      mediated diseases independent of environmental factors. Our findings provide
      novel mechanistic insights into dyslipidemia and immune-mediated diseases and may
      have implications for therapeutic trials involving lipid-lowering and anti
      inflammatory agents. 

PMID- 25853427
TI  - A novel pore-forming toxin in type A Clostridium perfringens is associated with
      both fatal canine hemorrhagic gastroenteritis and fatal foal necrotizing
      enterocolitis.
AB  - A role for type A Clostridium perfringens in acute hemorrhagic and necrotizing
      gastroenteritis in dogs and in necrotizing enterocolitis of neonatal foals has
      long been suspected but incompletely characterized. The supernatants of an
      isolate made from a dog and from a foal that died from these diseases were both
      found to be highly cytotoxic for an equine ovarian (EO) cell line. Partial genome
      sequencing of the canine isolate revealed three novel putative toxin genes
      encoding proteins related to the pore-forming Leukocidin/Hemolysin Superfamily;
      these were designated netE, netF, and netG. netE and netF were located on one
      large conjugative plasmid, and netG was located with a cpe enterotoxin gene on a
      second large conjugative plasmid. Mutation and complementation showed that only
      netF was associated with the cytotoxicity. Although netE and netG were not
      associated with cytotoxicity, immunoblotting with specific antisera showed these
      proteins to be expressed in vitro. There was a highly significant association
      between the presence of netF with type A strains isolated from cases of canine
      acute hemorrhagic gastroenteritis and foal necrotizing enterocolitis. netE and
      netF were found in all cytotoxic isolates, as was cpe, but netG was less
      consistently present. Pulsed-field gel electrophoresis showed that netF-positive
      isolates belonged to a clonal population; some canine and equine netF-positive
      isolates were genetically indistinguishable. Equine antisera to recombinant Net
      proteins showed that only antiserum to rNetF had high supernatant cytotoxin
      neutralizing activity. The identifica-tion of this novel necrotizing toxin is an
      important advance in understanding the virulence of type A C. perfringens in
      specific enteric disease of animals. 

PMID- 25853428
TI  - Antioxidant and angiostatic effect of Spirulina platensis suspension in complete
      Freund's adjuvant-induced arthritis in rats.
AB  - BACKGROUND: Currently, natural products have built a well-recognized role in the
      management of many degenerative diseases, mainly rheumatoid arthritis. Recent
      studies suggest that Spirulina, a unicellular blue-green alga, may have a variety
      of health benefits and curative properties and is also competent of acting as an
      anti-inflammatory, antioxidant and recently anti-angiogenic agent. In the present
      study, the antioxidant and the immunomodulatory effect of Spirulina platensis as
      well as its anti-angiogenic effect against complete Freund's adjuvant-induced
      arthritis (AIA) in rat model were tested. RESULTS: We found that the development
      of arthritis was concealed; moreover it successfully inhibited the development of
      macroscopic as well as microscopic and histopathological lesions in AIA rats when
      compared to control. Spirulina treated group showed a higher survival rate and
      moreover, it reduced the clinical score of RA in a dose dependent manner.
      Furthermore, Spirulina decreased serum levels of COX-2, TNF-alpha, IL-6, TBARS,
      VEGF and increased serum levels of GSH compared to the RA non-treated group.
      CONCLUSIONS: The present study concluded that Spirulina is able to restrain the
      changes produced through adjuvant-induced arthritis. The suppressing effect of
      Spirulina could be attributed, at least in part, to anti-inflammatory,
      antioxidant and anti-angiogenic properties.

PMID- 25853429
TI  - Testing pancreatic islet function at the single cell level by calcium influx with
      associated marker expression.
AB  - Studying the response of islet cells to glucose stimulation is important for
      understanding cell function in healthy and disease states. Most functional assays
      are performed on whole islets or cell populations, resulting in averaged
      observations and loss of information at the single cell level. We demonstrate
      methods to examine calcium fluxing in individual cells of intact islets in
      response to multiple glucose challenges. Wild-type mouse islets predominantly
      contained cells that responded to three (out of three) sequential high glucose
      challenges, whereas cells of diabetic islets (db/db or NOD) responded less
      frequently or not at all. Imaged islets were also immunostained for endocrine
      markers to associate the calcium flux profile of individual cells with gene
      expression. Wild-type mouse islet cells that robustly fluxed calcium expressed
      beta cell markers (INS/NKX6.1), whereas islet cells that inversely fluxed at low
      glucose expressed alpha cell markers (GCG). Diabetic mouse islets showed a higher
      proportion of dysfunctional beta cells that responded poorly to glucose
      challenges. Most of the failed calcium influx responses in beta cells were
      observed in the second and third high glucose challenges, emphasizing the
      importance of multiple sequential glucose challenges for assessing the full
      function of islet cells. Human islet cells were also assessed and showed
      functional alpha and beta cells. This approach to analyze islet responses to
      multiple glucose challenges in correlation with gene expression assays expands
      the understanding of beta cell function and the diseased state. 

PMID- 25853430
TI  - A water-stable lanthanide-functionalized MOF as a highly selective and sensitive
      fluorescent probe for Cd(2.).
AB  - A highly selective and sensitive fluorescent sensor for Cd(2+) in aqueous
      solution based on a lanthanide post-functionalized metal-organic framework was
      developed. 

PMID- 25853431
TI  - Coupling between Pentachlorophenol Dechlorination and Soil Redox As Revealed by
      Stable Carbon Isotope, Microbial Community Structure, and Biogeochemical Data.
AB  - Carbon isotopic analysis and molecular-based methods were used in conjunction
      with geochemical data sets to assess the dechlorination of pentachlorophenol
      (PCP) when coupled to biogeochemical processes in a mangrove soil having no prior
      history of anthropogenic contamination. The PCP underwent 96% dechlorination in
      soil amended with acetate, compared to 21% dehalogenation in control soil. Carbon
      isotope analysis of residual PCP demonstrated an obvious enrichment of 13C
      (epsilonC, -3.01+/-0.1%). Molecular and statistical analyses demonstrated that
      PCP dechlorination and Fe(III) reduction were synergistically combined electron
      accepting processes. Microbial community analysis further suggested that enhanced
      dechlorination of PCP during Fe(III) reduction was mediated by members of the
      multifunctional family of Geobacteraceae. In contrast, PCP significantly
      suppressed the growth of SO4(2-) reducers, which, in turn, facilitated the
      production of CH4 by diversion of electrons from SO4(2-) reduction to
      methanogenesis. The integrated data regarding stoichiometric alterations in this
      study gives direct evidence showing PCP, Fe(III), and SO4(2-) reduction, and CH4
      production are coupled microbial processes during changes in soil redox.

PMID- 25853432
TI  - Practice explains abolished behavioural adaptation after human dorsal anterior
      cingulate cortex lesions.
AB  - The role of mid-cingulate cortex (MCC), also referred to as dorsal anterior
      cingulate cortex, in regulating cognitive control is a topic of primary
      importance in cognitive neuroscience. Although many studies have shown that MCC
      responds to cognitive demands, lesion studies in humans are inconclusive
      concerning the causal role of the MCC in the adaptation to these demands. By
      elegantly combining single-cell recordings with behavioural methods, Sheth et al.
      [Sheth, S. et al. Human dorsal anterior cingulate cortex neurons mediate ongoing
      behavioural adaptation. Nature 488, 218-22 (2012).] recently were able to show
      that neurons in MCC encode cognitive demand. Importantly, this study also claimed
      that focal lesions of the MCC abolished behavioural adaptation to cognitive
      demands. Here we show that the absence of post-cingulotomy behavioural adaptation
      reported in this study may have been due to practice effects. We run a control
      condition where we tested subjects before and after a dummy treatment, which
      substituted cingulotomy with a filler task (presentation of a documentary). The
      results revealed abolished behavioural adaptation following the dummy treatment.
      Our findings suggest that future work using proper experimental designs is needed
      to advance the understanding of the causal role of the MCC in behavioural
      adaptation. 

PMID- 25853434
TI  - Pdots, a new type of nanoparticle, bind to mTHPC via their lipid modified surface
      and exhibit very high FRET efficiency between the core and the sensitizer.
AB  - Pdots are a new type of nanoparticle which exhibit strong potential for future
      applications in biophysics and cell biology. They are composed of organic
      chromophoric polymers, whose surfaces can be modified with different amphiphilic
      polymers, such as PEGylated lipids to make them very stable as colloids in water.
      We demonstrate in this manuscript that the lipid nano-coating around the Pdot can
      bind very efficiently to amphiphilic molecules, such as photosensitizers e.g.
      meso-tetrahydroxyphenylchlorin (mTHPC). As a result the sensitizer is brought
      into very close contact with the cores of the Pdots, and resonance energy
      transfer from the core to the sensitizer is very efficient; in some cases it is
      close to 1. We show the spectroscopic properties of two types of Pdots; their
      sizes, which are in the 13-47 nm range, depend on the kind of polymer and the
      length of the PEGylated lipid chains that wrap it. We measured the efficiency of
      FRET by investigating the decrease in donor intensity or its lifetime upon
      binding with mTHPC. We also show the relative yields of singlet oxygen that are
      obtained via two pathways: by exciting the Pdots which transfer the energy to the
      attached sensitizer, or by exciting the sensitizer directly. This methodology
      could be used to enhance the use of a photosensitizer by employing both pathways
      in parallel. 

PMID- 25853433
TI  - Deleterious effects of endocrine disruptors are corrected in the mammalian
      germline by epigenome reprogramming.
AB  - BACKGROUND: Exposure to environmental endocrine-disrupting chemicals during
      pregnancy reportedly causes transgenerationally inherited reproductive defects.
      We hypothesized that to affect the grandchild, endocrine-disrupting chemicals
      must alter the epigenome of the germ cells of the in utero-exposed G1 male fetus.
      Additionally, to affect the great-grandchild, the aberration must persist in the
      germ cells of the unexposed G2 grandchild. RESULTS: Here, we treat gestating
      female mice with vinclozolin, bisphenol A, or di-(2-ethylhexyl)phthalate during
      the time when global de novo DNA methylation and imprint establishment occurs in
      the germ cells of the G1 male fetus. We map genome-wide features in purified G1
      and G2 prospermatogonia, in order to detect immediate and persistent epigenetic
      aberrations, respectively. We detect changes in transcription and methylation in
      the G1 germline immediately after endocrine-disrupting chemicals exposure, but
      changes do not persist into the G2 germline. Additional analysis of genomic
      imprints shows no persistent aberrations in DNA methylation at the differentially
      methylated regions of imprinted genes between the G1 and G2 prospermatogonia, or
      in the allele-specific transcription of imprinted genes between the G2 and G3
      soma. CONCLUSIONS: Our results suggest that endocrine-disrupting chemicals exert
      direct epigenetic effects in exposed fetal germ cells, which are corrected by
      reprogramming events in the next generation. Avoiding transgenerational
      inheritance of environmentally-caused epigenetic aberrations may have played an
      evolutionary role in the development of dual waves of global epigenome
      reprogramming in mammals.

PMID- 25853435
TI  - ABHD4 regulates multiple classes of N-acyl phospholipids in the mammalian central
      nervous system.
AB  - N-Acyl phospholipids are atypical components of cell membranes that bear three
      acyl chains and serve as potential biosynthetic precursors for lipid mediators
      such as endocannabinoids. Biochemical studies have implicated ABHD4 as a brain N
      acyl phosphatidylethanolamine (NAPE) lipase, but in vivo evidence for this
      functional assignment is lacking. Here, we describe ABHD4(-/-) mice and their
      characterization using untargeted lipidomics to discover that ABHD4 regulates
      multiple classes of brain N-acyl phospholipids. In addition to showing reductions
      in brain glycerophospho-NAEs (GP-NAEs) and plasmalogen-based lyso-NAPEs (lyso
      pNAPEs), ABHD4(-/-) mice exhibited decreases in a distinct set of brain lipids
      that were structurally characterized as N-acyl lysophosphatidylserines (lyso
      NAPSs). Biochemical assays confirmed that NAPS lipids are direct substrates of
      ABHD4. These findings, taken together, designate ABHD4 as a principal regulator
      of N-acyl phospholipid metabolism in the mammalian nervous system.

PMID- 25853436
TI  - An anti-B7-H4 antibody-drug conjugate for the treatment of breast cancer.
AB  - B7-H4 has been implicated in cancers of the female reproductive system and
      investigated for its possible use as a biomarker for cancer, but there are no
      preclinical studies to demonstrate that B7-H4 is a molecular target for
      therapeutic intervention of cancer. We provide evidence that the prevalence and
      expression levels of B7-H4 are high in different subtypes of breast cancer and
      that only a few normal tissues express B7-H4 on the cell membrane. These profiles
      of low normal expression and upregulation in cancer provide an opportunity for
      the use of antibody-drug conjugates (ADCs), cytotoxic drugs chemically linked to
      antibodies, for the treatment of B7-H4 positive cancers. We have developed an ADC
      specific to B7-H4 that uses a linker drug consisting of a potent antimitotic,
      monomethyl auristatin E (MMAE), linked to engineered cysteines (THIOMAB) via a
      protease labile linker. We will refer to ADCs that use the THIOMAB format as TDCs
      to help distinguish the format from standard MC-vc-MMAE ADCs that are conjugated
      to the interchain disulfide bonds. Anti-B7-H4 (h1D11)-MC-vc-PAB-MMAE (h1D11 TDC)
      produced durable tumor regression in cell line and patient-derived xenograft
      models of triple-negative breast cancer. It also binds rat B7-H4 with similar
      affinity to human and allowed us to test for target dependent toxicity in rats.
      We found that our anti-B7-H4 TDC has toxicity findings similar to untargeted TDC.
      Our results validate B7-H4 as an ADC target for breast cancer and support the
      possible use of this TDC in the treatment of B7-H4(+) breast cancer. 

PMID- 25853437
TI  - Outpatient Cervical and Lumbar Spine Surgery is Feasible and Safe: A Consecutive
      Single Center Series of 1449 Patients.
AB  - BACKGROUND: There is an increasing demand for surgery of degenerative spinal
      disease. Limited healthcare resources draw attention to the need for cost
      effective treatments. Outpatient surgery, when safe and feasible, is more cost
      effective than inpatient surgery. OBJECTIVE: To study types and rates of
      complications after outpatient lumbar and cervical spine decompressions. METHODS:
      Complications were recorded prospectively in 1449 (1073 lumbar, 376 cervical)
      outpatients undergoing microsurgical decompression for degenerative spinal
      disease at the private Oslofjord Clinic from 2008 to 2013. RESULTS: Surgical
      mortality was 0%. A total of 51 (3.5%) minor and major complications were
      recorded in 51 patients. Three (0.2%) patients had to be admitted to a hospital
      the day of surgery. Twenty-two (1.5%) patients were admitted to a hospital within
      3 months due to surgery-related events. The encountered complications were
      postoperative hematoma (0.6%), neurological deterioration (0.3%), deep wound
      infection (0.9%), dural lesions with cerebrospinal fluid leakage (1.0%),
      persistent dysphagia (0.1%), persistent hoarseness (0.1%), and severe
      pain/headache (0.4%). All of the life-threatening hematomas were detected within
      6 and 3 hours after cervical and lumbar surgery, respectively. CONCLUSION: This
      series of 1449 consecutive outpatient microsurgical spine decompressions adds to
      the growing literature in favor of outpatient spinal surgery in properly selected
      patients. In our study, 99.8% of the patients were successfully discharged either
      to their homes or to a hotel on the day of surgery. The overall complication rate
      was 3.5%, surgical mortality was 0%, and only 1.5% had to be admitted to a
      hospital within 3 months after surgery.

PMID- 25853438
TI  - Size-optimized galactose-capped gold nanoparticles for the colorimetric detection
      of heat-labile enterotoxin at nanomolar concentrations.
AB  - The development of a galactose-capped gold nanoparticle-based colorimetric sensor
      for the detection of the lectin heat-labile enterotoxin is reported. Heat-labile
      enterotoxin is one of the pathogenic agents responsible for the intestinal
      disease called 'traveller's diarrhoea'. By means of specific interaction between
      galactose moieties attached to the surface of gold nanoparticles and receptors on
      the B-subunit of heat-labile enterotoxin (LTB), the gold nanoparticles reported
      here act as an efficient colorimetric sensor, which can detect the toxin at
      nanomolar concentrations. The effect of gold nanoparticle size on the detection
      sensitivity was investigated in detail. Amongst the various sizes of gold
      nanoparticles studied (2, 7, 12, and 20 nm), the 12 nm sized gold nanoparticles
      were found to be the most efficient, with a minimum heat-labile enterotoxin
      detection concentration of 100 nM. The red to purple colour change of the gold
      nanoparticle solution occurred within two minutes, indicating rapid toxin
      sensing. 

PMID- 25853439
TI  - Plasmon enhancement of luminescence upconversion.
AB  - Frequency conversion has always been an important topic in optics. Nonlinear
      optics has traditionally focused on frequency conversion based on nonlinear
      susceptibility but with the recent development of upconversion nanomaterials,
      luminescence upconversion has begun to receive renewed attention. While
      upconversion nanomaterials open doors to a wide range of new opportunities, they
      remain too inefficient for most applications. Incorporating plasmonic
      nanostructures provides a promising pathway to highly efficient upconversion.
      Naturally, a plethora of theoretical and experimental studies have been published
      in recent years, reporting enhancements up to several hundred. It is however
      difficult to make meaningful comparisons since the plasmonic fields are highly
      sensitive to the local geometry and excitation condition. Also, many luminescence
      upconversion processes involve multiple steps via different physical mechanisms
      and the overall output is often determined by a delicate interplay among them.
      This review is aimed at offering a comprehensive framework for plasmon enhanced
      luminescence upconversion. We first present quantum electrodynamics descriptions
      for all the processes involved in luminescence upconversion, which include
      absorption, emission, energy transfer and nonradiative transitions. We then
      present a bird's eye view of published works on plasmon enhanced upconversion,
      followed by more detailed discussion on comparable classes of nanostructures, the
      effects of spacer layers and local heating, and the dynamics of the plasmon
      enhanced upconversion process. Plasmon enhanced upconversion is a challenging and
      exciting field from the fundamental scientific perspective and also from
      technological standpoints. It offers an excellent system to study how optical
      processes are affected by the local photonic environment. This type of research
      is particularly timely as the plasmonics is placing heavier emphasis on
      nonlinearity. At the same time, efficient upconversion could make a significant
      impact on many applications including solar energy conversion and biomedical
      imaging. The marriage of luminescent materials research with nanophotonics
      currently being initiated with plasmon enhanced upconversion research explores a
      new frontier in photonics that could potentially spawn many exciting new fields. 

PMID- 25853440
TI  - Selectfluor-Promoted Sequential Reactions via Allene Intermediates: Metal-Free
      Construction of Fused Polycyclic Skeletons.
AB  - Polycyclic skeletons are present in numerous important compounds, such as
      synthetic intermediates and target molecules of biological interest. In this
      paper, a Selectfluor-promoted construction of polycyclic skeletons with high
      synthetic efficiency was developed. 

PMID- 25853441
TI  - Comparision of surgical outcomes of intraocular lens refixation and intraocular
      lens exchange with perfluorocarbon liquid and fibrin glue-assisted sutureless
      scleral fixation.
AB  - AIM: The purpose of this study was to compare the surgical outcomes of
      intraocular lens (IOL) refixation with intraocular lens exchange using
      perfluorocarbon liquid (PFCL) and fibrin glue-assisted sutureless scleral
      fixation surgery in patients with dislocation of the IOL. METHODS: Twenty-five
      eyes of 25 patients who underwent surgery for dislocated IOLs with PFCL and
      fibrin glue-assisted scleral fixation were studied; 13 eyes experienced IOL
      refixation (in-the-bag and out-of-the-bag), and 12 eyes experienced IOL exchange.
      Preoperative and postoperative clinical features from patient charts and 25 eyes
      with >6 months' follow-up information were reviewed and analyzed. RESULTS: At
      postoperative 6 months, best-corrected visual acuity (BCVA) and spherical
      equivalent of IOL refixation and exchange were significantly improved (P=0.042,
      P=0.001), and endothelial cell density was significantly decreased in the two
      groups with no significant difference between them. Surgically induced
      astigmatism of IOL refixation improved from 0.90+/-0.47 to 0.61+/-0.37 (P=0.012),
      and IOL exchange improved from 1.17+/-0.64 to 0.73+/-0.37 (P=0.037) at
      postoperative 6 months, with no significant difference between the two groups.
      Complications occurred in four eyes in the IOL refixation group and in three eyes
      in the IOL exchange group. CONCLUSION: PFCL and fibrin glue-assisted IOL
      sutureless scleral refixation or exchanged fixation was an effective surgical
      treatment for IOL dislocation. Also, because postoperative BCVA, surgical
      outcomes, and complications did not differ significantly between IOL refixation
      and exchange surgery, if IOL exchange surgery is not indicated, IOL refixation
      surgical techniques should be considered.

PMID- 25853443
TI  - Incidence and indications for pars plana vitrectomy following the treatment of
      posterior uveal melanomas in Scotland.
AB  - BACKGROUND: Globe-sparing treatments such as plaque brachytherapy, local or
      endoresection, and proton beam therapy (PBT) are the treatments of choice for
      posterior uveal melanoma. However, both early and late complications can arise
      from these techniques, including vitreous haemorrhage (VH) and retinal detachment
      (RD). Choroidal melanomas in Scotland are managed by a single unit, the Scottish
      Ocular Oncology Service (SOOS). METHODS: Indications and outcomes from surgery
      were analysed for patients undergoing vitrectomy following treatment for uveal
      melanoma in the SOOS between 1998 and 2013. RESULTS: Seventeen from 715 cases
      (2.4%) required vitrectomy, of which 8/445 (1.8%) followed plaque brachytherapy,
      7/43 (16.3%) combined local resection and brachytherapy, and 2/227 (0.9%) PBT.
      Case notes were reviewed for 16/17 cases, with surgery indicated for VH in 10
      (63%), RD in 5 (31%), and combined VH/RD in 1 (6%). The median interval from
      initial tumour treatment to vitrectomy was 5.8 months (range 10 days to 8.8
      years). Ten (63%) required early vitrectomy (within 6 months), of which the
      majority (70%) followed combined resection/brachytherapy. Six (37%) required late
      vitrectomy (after 6 months), of which all were non-clearing VH following plaque
      brachytherapy, with proliferative retinopathy in 4/6 (67%), and tumour recurrence
      in 2/6 (33%). Overall vision improved in 8 eyes (50%), remained the same in 2
      (12.5%), and deteriorated in 6 (37.5%). CONCLUSIONS: Early vitrectomy was most
      commonly indicated for RD following local resection, and late vitrectomy for VH
      due to radiation retinopathy. The majority of patients undergoing vitrectomy
      gained or maintained vision.

PMID- 25853442
TI  - Association of histone acetylation at the ACTA2 promoter region with epithelial
      mesenchymal transition of lens epithelial cells.
AB  - PURPOSE: Epithelial mesenchymal transition (EMT) plays a central role in the
      development of fibrotic complications of the lens. The current study is designed
      to check whether EMT of lens epithelial cells (LECs) is regulated by epigenetic
      modifications and to evaluate the effect of Trichostatin-A (TSA) on the
      transforming growth factor-beta (TGF-beta)-induced EMT. METHODS: Fetal human LECs
      (FHL124) were treated with TGF-beta2 in the presence or absence of TSA. Levels of
      mRNA, protein, as well as localization of alpha-smooth muscle actin (alphaSMA)
      were studied along with migration of LECs. Acetylation of histone H4 was analyzed
      and chromatin immunoprecipitation (ChIP) was carried out to study the level of
      acetylated histone H4 at the promoter of alphaSMA gene (ACTA2). Student's t-test
      was used for statistical analysis. RESULTS: TGF-beta2 treatment resulted in
      myofibroblast-like changes and increased migratory capacity of FHL124. Protein
      and mRNA expression of alphaSMA increased, and immunofluorescence revealed
      presence of extensive stress fibers. TSA treatment preserved epithelial
      morphology, retarded cell migration, and abrogated an increase in alphaSMA
      levels. TSA led to the accumulation of acetylated histone H4 that was reduced on
      TGF-beta2 treatment. However, increased level of histone H4 acetylation was found
      at the ACTA2 promoter region during TGF-beta treatment. CONCLUSIONS: The
      increased level of alphaSMA, a hallmark of EMT in LECs, is associated with
      increased level of histone H4 acetylation at its promoter region, and TSA helps
      in suppressing EMT by epigenetically reducing this level. TSA thus shows
      promising potential in management of fibrotic conditions of the lens.

PMID- 25853444
TI  - Apolipoprotein B: novel indicator of elevated intraocular pressure.
AB  - PURPOSE: Many studies have reported associations between elevated intraocular
      pressure (IOP) and systemic health parameters, which suggest a common mechanism
      links IOP elevation and various related cardiometabolic risk factors.
      Furthermore, according to a recent study, serum apolipoprotein B (APO B) level is
      a predictor of coronary artery disease. This study was undertaken to analyse the
      relationship between serum apolipoprotein levels and IOP. METHODS: Healthy people
      (28,852) who attended a community hospital for a health checkup between January
      2011 and December 2013 were enroled in the study. We measured age, body mass
      index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), serum
      levels of total cholesterol (TC), triglyceride (TG), high-density lipoprotein
      cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and
      apolipoprotein A1 (APO A1) and APO B, APO B/APO A1 ratios, and IOP. RESULTS:
      Univariate regression analysis showed IOP was positively correlated with BMI,
      SBP, DBP, TC, LDL-C, TG, APO B, and APO B/APO A1 (P<0.001), and negatively
      correlated with HDL-C (P<0.001). On the other hand, multivariate regression
      analysis adjusted for age, BMI, SBP, and DBP, revealed IOP was positive
      correlated with TC, TG, LDL-C, APO B, and APO B/APO A1, and negatively correlated
      with HDL-C (all <0.05). CONCLUSIONS: Among the various lipid profiles
      investigated, APO B was found to be most strongly correlated with IOP, regardless
      of sex. Additional studies are required to confirm the validity of apolipoprotein
      level as an index for predicting IOP.

PMID- 25853445
TI  - The usefulness of the Retinomax autorefractor for childhood screening validated
      against a Danish preterm cohort examined at the age of 4 years.
AB  - BACKGROUND AND PURPOSE: Refractometers have gained a foothold in childhood
      screening for ophthalmic disorders. Given the results of an ophthalmic follow-up
      of an extremely preterm Danish cohort, the results of the Retinomax autorefractor
      were further evaluated. MATERIALS AND METHODS: A nationwide cohort of infants
      born before gestational age 28 weeks (n=178) and 56 term controls were examined
      at the age of 4 years. Refraction was given as the cycloplegic Retinomax value.
      For this study, we analysed the equipment's confidence value on the printout and
      equipment-induced myopization (as the difference between refraction measured
      before and after topical cyclopentholate 1%), both items hypothetical with a view
      to having identified factual ophthalmic deviations. RESULTS: Thirty-two of 42
      eyes with visual acuity <=0.4 had high Retinomax confidence values (8-9); the
      Retinomax values were also high in 10 of 12 children with strabismus and lack of
      stereopsis. Low values (1-6) were recorded in 11 single eyes, 5 of which were
      normal (false positives). Three children already known to have low vision were
      unable to cooperate. The overall mean value for equipment-induced myopization was
      1.9 D (range, 0-6.87 D). Myopization showed no correlation with visual acuity and
      corneal curvature, and a weak positive correlation with refractive value
      disappeared when the myopic outliers were excluded. CONCLUSIONS: The hand-held
      Retinomax seemed to be reliable for assessing refraction in 4-year-old children,
      provided a cycloplegic agent is applied; if used alone, the Retinomax would have
      missed several cases of ophthalmic deviation during screening. Equipment-induced
      myopization was not indicative.

PMID- 25853446
TI  - Corneal collagen crosslinking for keratoconus or corneal ectasia without
      epithelial debridement.
AB  - PURPOSE: Corneal collagen crosslinking (CXL) is a relatively new technique to
      reduce the progression of keratoconus. The technique can be performed with or
      without complete debridement of the corneal epithelium. We describe a novel
      intermediate technique involving mechanical disruption of the epithelium, and
      evaluate its safety and efficacy. METHODS: The case notes of 128 eyes with
      progressive keratoconus or iatrogenic corneal ectasia who had undergone CXL using
      the epithelial disruption technique were retrospectively reviewed. Thin corneas
      were treated with hypotonic riboflavin. All others were treated with an isotonic
      solution. Note was made of preoperative and postoperative parameters, including
      uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA),
      refraction, endothelial cell count, and corneal tomography. Occurrence of
      procedure-related complications was recorded. Statistical analyses were performed
      using the paired sample t-test and Wilcoxon signed-rank test, with a level of
      P<0.05 being accepted as statistically significant. RESULTS: At 12 months, 41.8%
      of patients treated with isotonic riboflavin had improved UCVA and 29.7% had
      improved BSCVA. Only 13.4% lost lines of UCVA and 14.9% lost BSCVA. Of the
      patients treated with hypotonic riboflavin, at 12 months, 75% demonstrated
      stability of BSCVA and 25% had stable Kmax. In addition, 25% showed improved
      visual acuity at 12 months, and 58.3% showed regression of their Kmax. Our rate
      of short-term complications was comparable to studies using complete epithelial
      removal. CONCLUSIONS: CXL with epithelial disruption is a safe and effective
      treatment for keratoconus or iatrogenic corneal ectasia, and may be better
      tolerated by patients than the epithelium-off technique.

PMID- 25853447
TI  - Anatomical and functional recurrence after dexamethasone intravitreal implants: a
      6-month prospective study.
AB  - PURPOSE: To evaluate the efficacy, safety, and delay of anatomical and functional
      recurrence after a first intravitreal injection of dexamethasone implant in eyes
      with cystoid macular edema (CME) secondary to retinal vein occlusion (RVO).
      METHODS: A 6-month prospective, monocentric and noncomparative case-series of 26
      eyes of 26 patients. Best-corrected visual acuity (BCVA) and central subfield
      thickness (CST) were measured at baseline and each visit at 1 week, and months 1,
      2, 3, 4, 5, and 6 after a first treatment. Primary efficacy outcome was the
      proportion of eyes with a minimum three-line improvement from baseline BCVA at
      each visit and at 6 months. We also defined different patterns of recurrence:
      qualitative anatomical recurrence, quantitative anatomical recurrence and
      functional recurrence. A P-value <5% was considered statistically significant.
      RESULTS: Mean population age was 69.3 years (SD=12.2; range=42-94 years). Mean ME
      duration before treatment was ~9.2 months (SD=11.43; range=0.4-40 months). Eighty
      eight percent of eyes achieved a three-line improvement from baseline at 2 months
      (P=0.02). The mean delay from baseline until qualitative anatomical, functional,
      or quantitative anatomical recurrence was 4.11 months (+/-0.86), 4.31 months (+/
      1.33), and 4.40 months (+/-1.14), respectively. Qualitative anatomical recurrence
      occurred on average 14.4 days (SD=42.18) before a minimum of one-line BCVA
      impairment (functional recurrence). CONCLUSION: Dexamethasone intravitreal
      treatment seems to be effective for ME after RVO even with long-duration ME or
      poor visual acuity before treatment. Other longer studies should assess the delay
      of recurrence after second and further treatments with DEX implants or combined
      therapies for ME after RVO.

PMID- 25853448
TI  - Ameliorative Effect of Adjunct Therapy of Metformin with Atorvastatin on
      Streptozotocin-induced Diabetes Mellitus in Rats.
AB  - Metformin has been used for the treatment of diabetes, whereas atorvastatin
      reduces the incidence of atherosclerosis and ischemic heart disease. Therefore,
      combined treatment with meformin plus atorvastatin may be beneficial in diabetic
      patients associated with cardiac disease. The present study was designed to
      evaluate the combination therapy of metformin and atorvastatin on streptozotocin
      induced diabetes mellitus in rats. Blood pressure, serum insulin, glucose, lipid
      profiles and antioxidant enzymes in pancreatic tissues were measured.
      Histopathological examination of pancreatic tissues was performed. Streptozotocin
      treated rats showed significant decrease in body weight and body mass index.
      Streptozotocin-treated rats showed a significant increase in the levels of blood
      pressure, serum glucose, triglycerides, total cholesterol and thiobarbituric acid
      reactive substance as well as a significant decrease in the levels of serum
      insulin, high density lipoprotein and reduced glutathione in pancreatic tissues.
      Administration of metformin plus atorvastatin for a period of 14 days
      significantly improved these biochemical parameters near to normal. The
      protective effect of metformin plus atorvaststin against streptozotocin-induced
      diabetes was further confirmed by histopathological examination. The results of
      present study suggest that metformin plus atorvastatin possess antioxidant
      activity and has a significant protective effect against streptozotocin-induced
      diabetes mellitus. 

PMID- 25853449
TI  - Chinese version of the Aging Perceptions Questionnaire (C-APQ): assessment of
      reliability and validity.
AB  - OBJECTIVES: To assess the reliability and validity of the Chinese version of
      Aging Perceptions Questionnaire (C-APQ). METHOD: Participants aged 65 years and
      over were recruited from February 2012 to November 2012. The Aging Perceptions
      Questionnaire was translated into Chinese version professionally. Content
      validity was examined by a panel of seven experts; item reliabilities were
      assessed by test-retest; internal consistency was assessed by Cronbach's alpha
      coefficient; half of the sample (N = 379) was selected to explore factorial
      structure of the C-APQ by exploratory factor analysis (EFA) and another half of
      the sample (N = 379) was selected to confirm the findings from the EFA by
      confirmatory factor analysis (CFA). Statistical package SPSS version 18.0 and
      Amos 17.0 were used for the analysis. RESULTS: The Cronbach's alpha coefficient
      of the C-APQ was 0.884. The test-retest reliability was satisfactory, with all
      intraclass correlation coefficients greater than 0.4. The overall content
      validity index was greater than 0.99. Seven factors (timeline acute/chronic,
      timeline cyclical, emotional representations, control positive, control negative,
      consequences positive and consequences negative) were identified in EFA and
      confirmed in CFA. CONCLUSION: The C-APQ could be a reliable and a valid measure
      of the self-perceptions of aging in the elderly in China, which may help to
      improve the life quality and extend longevity of the elderly.

PMID- 25853450
TI  - Effects of morphine and midazolam on pharyngeal function, airway protection, and
      coordination of breathing and swallowing in healthy adults.
AB  - BACKGROUND: Drugs used for sedation in anesthesia and intensive care may cause
      pharyngeal dysfunction and increased risk for aspiration. In this study, the
      authors investigate the impact of sedative doses of morphine and midazolam on
      pharyngeal function during swallowing and coordination of breathing and
      swallowing. METHODS: Pharyngeal function, coordination of breathing and
      swallowing, and level of sedation were assessed by manometry, videoradiography,
      measurements of respiratory airflow, and a visual analog scale in 32 healthy
      volunteers (age 19 to 35 yr). After baseline recordings, morphine (0.1 mg/kg) or
      midazolam (0.05 mg/kg) was administered intravenously for 20 min, followed by
      recordings at 10 and 30 min after the end of infusion. RESULTS: Pharyngeal
      dysfunction, seen as misdirected or incomplete swallowing or penetration of bolus
      to the airway, increased after morphine infusion to 42 and 44% of swallows
      compared with 17% in baseline recordings. Midazolam markedly increased incidence
      of pharyngeal dysfunction from 16 to 48% and 59%. Morphine prolonged apnea before
      swallowing, and midazolam increased the number of swallows followed by
      inspiration. CONCLUSION: Morphine and midazolam in dosages that produce sedation
      are associated with increased incidence of pharyngeal dysfunction and
      discoordinated breathing and swallowing, a combination impairing airway
      protection and potentially increasing the risk for pulmonary aspirations.

PMID- 25853451
TI  - What would a proper explanation of anesthesia look like?

PMID- 25853454
TI  - Everyone's got it ... it must be familial.

PMID- 25853455
TI  - A quick review of the cutaneous findings of the deadly scourge Ebola virus.

PMID- 25853456
TI  - Frostbite and chilblains in Upton Sinclair's The Jungle.

PMID- 25853457
TI  - Scurvy: curse and cure in new France.

PMID- 25853459
TI  - Electron-Withdrawing beta-Substituent, Ring-Strain, and Ortho Effects on
      Reactivity, Selectivity, and Stability of o-Alkoxybenzyl Carbocations.
AB  - o-Alkoxybenzyl carbocations 1 and 2 were generated by laser flash photolysis of
      the corresponding o-alkoxybenzyl alcohols 3 and 4 to understand how the electron
      withdrawing beta-substituent, the ring-strain, and the ortho effects affect the
      reactivity (electrophilicity), selectivity, and stability of 1 and 2, and to fit
      the electrophilicity of 1 and 2 into the current carbocation electrophilicity
      scale (E). Our finding is that both the electron-withdrawing beta-substituent and
      the ring-strain effects make 1 less stable than 2 by 3.0 kcal/mol. These effects
      plus the ortho effect of 2 make 1 more reactive than 2, but the selectivity of 1
      and 2 toward amine nucleophiles is almost the same within experimental errors.
      The electrophilicity of 1 and 2 has been fit into the current carbocation
      electrophilicity scale (E) quite well. 

PMID- 25853460
TI  - Mandatory Naptimes in Child Care and Children's Nighttime Sleep.
AB  - OBJECTIVES: To examine the relationship between mandatory naptimes in child care
      and children's nighttime sleep duration, both concurrently and 12 months later
      once in school. METHODS: A sample of 168 children (50-72 months; 55% males)
      attending licensed child care centers were observed across their morning and
      throughout their scheduled naptime. Mandatory naptime was determined as the
      period in which children were not permitted any alternative activity except lying
      on their bed. Teachers reported each child's napping in child care. Nighttime and
      total sleep duration was reported by parents at 2 time points, in child care and
      in the second semester of their first school year. General linear models were
      used to examine group differences in sleep duration between children experiencing
      0 to 60 minutes and >60 minutes of mandatory naptime, adjusting for key
      confounders. Path analysis was conducted to test a mediation model in which
      mandatory naptime is associated with nighttime sleep duration through increased
      napping in child care. RESULTS: Children who experienced >60 minutes of mandatory
      naptime in child care had significantly less nighttime sleep than those with 0 to
      60 minutes of mandatory naptime. This difference persisted at 12-month follow-up,
      once children were in school. Napping in child care mediated the relationship
      between mandatory naptime and duration of nighttime sleep. CONCLUSIONS: Exposure
      to mandatory naptimes of >60 minutes in child care is associated with decreased
      duration of nighttime sleep that endures beyond child care attendance. Given the
      large number of children who attend child care, sleep practices within these
      settings present an important focus for child health.

PMID- 25853461
TI  - Implementing quality by design for biotech products: Are regulators on track?
AB  - Quality by design (QbD) is an innovative approach to drug development that has
      started to be implemented into the regulatory framework, but currently mainly for
      chemical drugs. The recent marketing authorization of the first monoclonal
      antibody developed using extensive QbD concepts in the European Union paves the
      way for future further regulatory approvals of complex products employing this
      cutting-edge technological concept. In this paper, we report and comment on
      insights and lessons learnt from the non-public discussions in the European
      Medicines Agency's Biologicals Working Party and Committee for Medicinal Products
      for Human Use on the key issues during evaluation related to the implementation
      of an extensive QbD approach for biotechnology-derived medicinal products.
      Sharing these insights could prove useful for future developments in QbD for
      biotech products in general and monoclonal antibodies in particular. 

PMID- 25853458
TI  - A novel mutation P112H in the TARDBP gene associated with frontotemporal lobar
      degeneration without motor neuron disease and abundant neuritic amyloid plaques.
AB  - INTRODUCTION: Although TDP-43 is the main constituent of the ubiquitinated
      cytoplasmic inclusions in the most common forms of frontotemporal lobar
      degeneration, TARDBP mutations are not a common cause of familial frontotemporal
      dementia, especially in the absence of motor neuron disease. RESULTS: We describe
      a pedigree presenting with a complex autosomal dominant disease, with a
      heterogeneous clinical phenotype, comprising unspecified dementia, parkinsonism,
      frontotemporal dementia and motor neuron disease. Genetic analyses identified a
      novel P112H TARDBP double variation located in exon 3 coding for the first RNA
      recognition motif of the protein (RRM1). This double mutation is probably
      pathogenic based on neuropathological findings, in silico prediction analysis and
      exome sequencing. The two autopsied siblings described here presented with
      frontotemporal dementia involving multiple cognitive domains and behavior but
      lacking symptoms of motor neuron disease throughout the disease course. The
      siblings presented with strikingly similar, although atypical, neuropathological
      features, including an unclassifiable TDP-43 inclusion pattern, a high burden of
      tau-negative beta-amyloid neuritic plaques with an AD-like biochemical profile,
      and an unclassifiable 4-repeat tauopathy. The co-occurrence of multiple protein
      inclusions points to a pathogenic mechanism that facilitates misfolded protein
      interaction and aggregation or a loss of TDP-43 function that somehow impairs
      protein clearance. CONCLUSIONS: TARDBP mutation screening should be considered in
      familial frontotemporal dementia cases, even without signs or symptoms of motor
      neuron disease, especially when other more frequent causes of genetic
      frontotemporal dementia (i.e. GRN, C9ORF72, MAPT) have been excluded and when
      family history is complex and includes parkinsonism, motor neuron disease and
      frontotemporal dementia. Further investigations in this family may provide
      insight into the physiological functions of TARDBP.

PMID- 25853462
TI  - Efficient microfluidic negative enrichment of circulating tumor cells in blood
      using roughened PDMS.
AB  - Efficient isolation strategies not based on epithelial biomarker expression are
      required to enable non-biased enrichment of circulating tumor cells (CTCs). CTCs
      undergoing epithelial-mesenchymal transition (EMT) may be prognostically
      relevant, and importantly are not detected with conventional epithelial based
      approaches such as CellSearch(r). A method for the non-biased isolation of cancer
      cells within a peripheral blood sample utilizing microfluidic mixing PDMS devices
      functionalized with anti-CD45 is reported. The introduction of micro and
      nanoscale roughness using a single step treatment with sulfuric acid
      significantly increases the binding yield of white blood cells (WBCs) to the anti
      CD45 conjugated surfaces. Up to 99.99% WBC depletion is achieved with a tumor
      cell recovery yield of 50%. This high level of CTC enrichment is expected to
      facilitate the detailed characterization of CTCs using for instance, imaging flow
      cytometry as demonstrated here. 

PMID- 25853463
TI  - Raman Characterization of Nanoparticle Transport in Microfluidic Paper-Based
      Analytical Devices (MUPADs).
AB  - There is great interest in the use of microfluidic paper-based analytical devices
      (MUPADs) for low-cost diagnostics. In this contribution, we illustrate the
      utility of Raman spectral imaging for both MUPAD characterization and for
      quantification of the transport of applied reagents and analytes within these
      devices. We evaluated the transport of nanoscale particles within MUPADs using a
      suite of differentially functionalized gold (AuNP) and silver (AgNP)
      nanoparticles with diameters of 8-64 nm. Nanoparticle transport within the
      cellulose matrix was characterized by collection of both Raman and surface
      enhanced Raman spectroscopy (SERS) spectral maps that enabled differentiation of
      cellulose fibers and characterization of analyte deposition patterns. The
      transport of citrate (cit), BSA, PEG, PVP, and DNA functionalized AuNP and AgNP
      in wax-printed MUPADs was primarily affected by nanoparticle surface chemistry
      rather than particle size or core composition. Sample pH (3-10) influenced the
      transport of 15 nm BSA-cit-AuNP, but not 15 nm cit-AuNP, because of the effects
      of solution pH on the charge and conformation of BSA. Derjaguin, Landau, Verwey,
      and Overbeek theory (DLVO) and extended DLVO (xDLVO) theory are used to explain
      the collected experimental results. 

PMID- 25853465
TI  - A growing interest for intellectual property in universities.

PMID- 25853464
TI  - microRNA-155, induced by interleukin-1beta, represses the expression of
      microphthalmia-associated transcription factor (MITF-M) in melanoma cells.
AB  - Loss of expression of surface antigens represents a significant problem for
      cancer immunotherapy. Microphthalmia-associated transcription factor (MITF-M)
      regulates melanocyte fate by driving expression of many differentiation genes,
      whose protein products can be recognized by cytolytic T lymphocytes. We
      previously reported that interleukin-1beta (IL-1beta) can downregulate MITF-M
      levels. Here we show that downregulation of MITF-M expression by IL-1beta was
      paralleled by an upregulation of miR-155 expression in four melanoma lines. We
      confirmed that miR-155 was able to target endogenous MITF-M in melanoma cells and
      demonstrated a role for miR-155 in the IL-1beta-induced repression of MITF-M by
      using an antagomiR. Notably, we also observed a strong negative correlation
      between MITF-M and miR-155 levels in a mouse model of melanoma. Taken together,
      our results indicate that MITF-M downregulation by inflammatory stimuli might be
      partly due to miR-155 upregulation. This could represent a novel mechanism of
      melanoma immune escape in an inflammatory microenvironment. 

PMID- 25853466
TI  - Will purple become the new orange? The new FDA purple book for biologics: what
      does the future hold?

PMID- 25853468
TI  - Transient receptor potential ankyrin 1 (TRPA1) antagonists.
AB  - The transient receptor potential ankyrin 1 (TRPA1) channel is an irritant sensor
      highly expressed on nociceptive neurons. The clinical use of TRPA1 antagonists is
      based on the concept that TRPA1 is active during disease states like neuropathic
      pain. Indeed, in Phase 2a proof-of-concept studies the TRPA1 antagonist GRC17536
      has shown efficacy in patients with painful diabetic neuropathy. Moreover, animal
      studies suggest that the therapeutic value of TRPA1 antagonists extends beyond
      pain to pruritus, asthma and cough with limited safety concerns. This review
      provides a comprehensive overview of the patent literature (since 2007) on small
      molecule inhibitors of the TRPA1 channel. Despite the clear progress, many
      unanswered questions remain. Future advancement to Phase 3 studies will assess
      the real translational potential of this research field. 

PMID- 25853469
TI  - Melanocortin-4 receptor modulators for the treatment of obesity: a patent
      analysis (2008-2014).
AB  - The central melanocortin system and particularly the melanocortin-4 receptor
      (MC4R) subtype, plays an important role in the regulation of body weight. The
      discovery of orally active MC4R agonists suitable for evaluation in human
      clinical trials as weight loss agents has attracted considerable interest over
      the past decade, but has proved challenging, in part because of cardiovascular
      and behavioral side effects. Currently, the only MC4R agonist in clinical trials
      is a peptide identified as RM-493. To avoid some of the undesirable side effects
      associated with MC4R activation, new pharmacological approaches for modulating
      the MC system have been investigated. In this article, we provide a review of the
      MC4R patent landscape from 2008 to 2014 and analyze the physicochemical
      properties of compounds described herein. 

PMID- 25853470
TI  - Click chemistry patents and their impact on drug discovery and chemical biology.
AB  - First introduced by K Barry Sharpless in 2001, the term 'click chemistry' soon
      became a widely used description of chemical reactions that proceed rapidly,
      cleanly and in a manner that is often compatible with aqueous solutions. Click
      chemistry is frequently employed throughout the process of drug discovery, and
      greatly helps advance research programs in the pharmaceutical industry. It
      facilitates library synthesis to support medicinal chemistry optimization, helps
      identify the targets and off-targets of drug candidates, and can facilitate the
      determination of drug efficacy in clinical trials. In the last decade, a large
      number of patent applications covering the various types and utilities of click
      chemistry have been filed. In this review, we provide the first analysis of click
      chemistry applications. 

PMID- 25853471
TI  - Corrigendum.

PMID- 25853472
TI  - Engelmann spruce site index models: a comparison of model functions and
      parameterizations.
AB  - Engelmann spruce (Picea engelmannii Parry ex Engelm.) is a high-elevation species
      found in western Canada and western USA. As this species becomes increasingly
      targeted for harvesting, better height growth information is required for good
      management of this species. This project was initiated to fill this need. The
      objective of the project was threefold: develop a site index model for Engelmann
      spruce; compare the fits and modelling and application issues between three model
      formulations and four parameterizations; and more closely examine the grounded
      Generalized Algebraic Difference Approach (g-GADA) model parameterization. The
      model fitting data consisted of 84 stem analyzed Engelmann spruce site trees
      sampled across the Engelmann Spruce - Subalpine Fir biogeoclimatic zone. The
      fitted models were based on the Chapman-Richards function, a modified Hossfeld IV
      function, and the Schumacher function. The model parameterizations that were
      tested are indicator variables, mixed-effects, GADA, and g-GADA. Model evaluation
      was based on the finite-sample corrected version of Akaike's Information Criteria
      and the estimated variance. Model parameterization had more of an influence on
      the fit than did model formulation, with the indicator variable method providing
      the best fit, followed by the mixed-effects modelling (9% increase in the
      variance for the Chapman-Richards and Schumacher formulations over the indicator
      variable parameterization), g-GADA (optimal approach) (335% increase in the
      variance), and the GADA/g-GADA (with the GADA parameterization) (346% increase in
      the variance). Factors related to the application of the model must be considered
      when selecting the model for use as the best fitting methods have the most
      barriers in their application in terms of data and software requirements. 

PMID- 25853473
TI  - Early intervention in thyroidectomy scars: demographics, symptoms, and
      prevention.
AB  - OBJECTIVE: Although hypertrophic scars are cosmetically problematic for patients
      following thyroidectomy, the associated risk factors are not well defined. Our
      objective was to determine the factors associated with hypertrophic scar
      development following thyroidectomy. METHOD: A retrospective chart review was
      performed collecting data on sex, age, body mass index (BMI), operation site,
      skin characteristics (pigmentation, erythema, elasticity, and hydration), and
      clinical scar characteristics (itching, tightening, induration, adhesion, and
      oedema). It was also noted if the patient had early scar intervention with
      intralesional steroid injection or non-ablative fractional laser irradiation, and
      preventive topical treatment agents. The effects of these factors were analysed
      using univariate and multivariate analyses. RESULTS: Data from 1141 patients
      showed the incidence of hypertrophic scars was 13.9%. Significant variables in
      univariate analysis were combined for multivariate analysis. Young age, high BMI,
      itching, tightening, induration, and adhesion were associated with hypertrophic
      scar formation. Early scar intervention, as well as the use of preventive topical
      agents, were associated with decreased hypertrophic scar formation. CONCLUSION:
      Based on our results, we suggest that dermatologists consider using non-ablative
      fractional laser, intralesional steroid injection, and topical preventive agents
      to lower the incidence of hypertrophic scars, especially in young patients or
      those with high BMI and/or clinical symptoms such as itching, tightening,
      induration, and adhesion.

PMID- 25853474
TI  - Use of an autologous leucocyte and platelet-rich fibrin patch on hard-to-heal
      DFUs: a pilot study.
AB  - OBJECTIVE: Leucopatch is a leukocyte and platelet-rich fibrin patch that provides
      concentrated blood cells and signal substances to the surface of an ulcer. It is
      produced by centrifugation of the patient's own venous blood. The aim of this
      pilot multicentre cohort study was to evaluate effects of the leucocyte patch in
      patients with hard-to-heal diabetic foot ulcers (DFUs). METHOD: Non-ischaemic
      Wagner grade 1 or 2 DFUs with a duration of more than 6 weeks and a maximal area
      of 10cm2 were included. Patients with >40% ulcer area change during a two-week
      run-in period were excluded. The treatment was applied once a week for up to 19
      treatments or until the foot ulcer was completely epithelialised. The primary
      endpoint was healing within 20 weeks. RESULTS: Of the 60 patients who gave
      consent 16 were excluded during run-in period, 44 patients initiated study
      treatment and 39 were included in the per-protocol analysis. Complete
      epithelisation was achieved in 34% (per-protocol analysis 36%) at 12 weeks and
      52% (59%) at 20 weeks. In patients with ulcer duration less than 6 months, 73% of
      ulcers healed within 20 weeks. Patients with healed ulcers had larger ulcer area
      reduction during the first two treatment weeks compared to non-healers. Adverse
      events were mild and rare. CONCLUSION: The leucocyte patch is well-tolerated,
      easy to use and has potential in the armamentarium of the DFU treatment, provided
      this outcome is confirmed in an appropriately powered randomised clinical trial.

PMID- 25853475
TI  - The prevention and management of pressure ulcers: summary of updated NICE
      guidance.

PMID- 25853476
TI  - Single-dose attenuated Vesiculovax vaccines protect primates against Ebola Makona
      virus.
AB  - The family Filoviridae contains three genera, Ebolavirus (EBOV), Marburg virus,
      and Cuevavirus. Some members of the EBOV genus, including Zaire ebolavirus
      (ZEBOV), can cause lethal haemorrhagic fever in humans. During 2014 an
      unprecedented ZEBOV outbreak occurred in West Africa and is still ongoing,
      resulting in over 10,000 deaths, and causing global concern of uncontrolled
      disease. To meet this challenge a rapid-acting vaccine is needed. Many vaccine
      approaches have shown promise in being able to protect nonhuman primates against
      ZEBOV. In response to the current ZEBOV outbreak several of these vaccines have
      been fast tracked for human use. However, it is not known whether any of these
      vaccines can provide protection against the new outbreak Makona strain of ZEBOV.
      One of these approaches is a first-generation recombinant vesicular stomatitis
      virus (rVSV)-based vaccine expressing the ZEBOV glycoprotein (GP) (rVSV/ZEBOV).
      To address safety concerns associated with this vector, we developed two
      candidate, further-attenuated rVSV/ZEBOV vaccines. Both attenuated vaccines
      produced an approximately tenfold lower vaccine-associated viraemia compared to
      the first-generation vaccine and both provided complete, single-dose protection
      of macaques from lethal challenge with the Makona outbreak strain of ZEBOV. 

PMID- 25853477
TI  - A smart tumor targeting peptide-drug conjugate, pHLIP-SS-DOX: synthesis and
      cellular uptake on MCF-7 and MCF-7/Adr cells.
AB  - Doxorubicin (DOX) is a potent anticancer drug for the treatment of tumors, but
      the poor specificity and multi-drug resistance (MDR) on tumor cells have
      restricted its application. Here, a pH and reduction-responsive peptide-drug
      conjugate (PDC), pHLIP-SS-DOX, was synthesized to overcome these drawbacks. pH
      low insertion peptide (pHLIP) is a cell penetrating peptide (CPP) with pH
      dependent transmembrane ability. And because of the unique cell membrane
      insertion pattern, it might reverse the MDR. The cellular uptake study showed
      that on both drug-sensitive MCF-7 and drug-resistant MCF-7/Adr cells, pHLIP-SS
      DOX obviously facilitated the uptake of DOX at pH 6.0 and the uptake level on MCF
      7/Adr cells was similar with that on MCF-7 cells, indicating that pHLIP-SS-DOX
      had the ability to target acidic tumor cells and reverse MDR. In vitro
      cytotoxicity study mediated by GSH-OEt demonstrated that the cytotoxic effect of
      pHLIP-SS-DOX was reduction responsive, with obvious cytotoxicity at pH 6.0; while
      it had poor cytotoxicity at pH 7.4, no matter with or without GSH-OEt
      pretreatment. This illustrated that pHLIP could deliver DOX into tumor cells with
      acidic microenvironment specifically and could not deliver drugs into normal
      cells with neutral microenvironment. In summary, pHLIP-SS-DOX is a promising
      strategy to target drugs to tumors and provides a possibility to overcome MDR. 

PMID- 25853478
TI  - Development and in vitro/in vivo evaluation of Zn-pectinate microparticles
      reinforced with chitosan for the colonic delivery of progesterone.
AB  - The colon is a promising target for drug delivery owing to its long transit time
      of up to 78 h, which is likely to increase the time available for drug
      absorption. Progesterone has a short elimination half-life and undergoes
      extensive first-pass metabolism, which results in very low oral bioavailability
      (~25%). To overcome these shortcomings, we developed an oral multiparticulate
      system for the colonic delivery of progesterone. Zn-pectinate/chitosan
      microparticles were prepared by ionotropic gelation and characterized for their
      size, shape, weight, drug entrapment efficiency, mucoadhesion and swelling
      behavior. The effect of cross-linking pH, cross-linking time and chitosan
      concentration on progesterone release were also studied. Spherical microparticles
      having a diameter of 580-720 um were obtained. Drug entrapment efficiency of ~75
      100% was obtained depending on the microparticle composition. Microparticle
      mucoadhesive properties were dependent on the pectin concentration, as well as
      the cross-linking pH. Progesterone release in simulated gastric fluids was
      minimal (3-9%), followed by burst release at pH 6.8 and a sustained phase at pH
      7.4. The in vivo study revealed that the microparticles significantly increased
      progesterone residence time in the plasma and increased its relative
      bioavailability to ~168%, compared to the drug alone. This study confirms the
      potential of Zn-pectinate/chitosan microparticles as a colon-specific drug
      delivery system able to enhance the oral bioavailability of progesterone or
      similar drugs.

PMID- 25853479
TI  - Pharmacokinetics and tissue distribution study in mice of triptolide-loaded lipid
      emulsion and accumulation effect on pancreas.
AB  - Triptolide (TP) shows strong anti-tumor activities on various cancer cells,
      especially on pancreatic cancer. TP inhibits HSP70 expression leading to cell
      death in pancreatic cancer cells and induces cell death by apoptotic and
      autophagic pathways. In order to increase the therapeutic index of TP, a novel
      intravenous TP-loaded delivery system, TP-loaded lipid emulsion (TP-LE), has been
      developed to treat solid tumor. In the present study, the preparation and
      characterization of TP-LE were described. The pharmacokinetics and tissue
      distribution study of TP-LE in mice were also evaluated. Results demonstrated
      that TP-LE had an average particle size of 154.6 nm, entrapment efficiency (EE%)
      of 87%, zeta potential of -0.903 mV and autoclaved stability. The pharmacokinetic
      study showed that blood concentrations of both TP-LE and TP reached a maximum at
      the end of intravenous administration (1.25 mg/kg) and declined rapidly within
      the first 10 min with a mean residence time (MRT) of about 10 min. In the tissue
      distribution study, a preferential accumulation and longer residence time of drug
      in pancreas were found in TP-LE. The AUC0-60min of TP-LE in pancreas was 2.19
      times in comparison to free TP, suggesting that the use of TP-LE conferred
      improvements in biodistribution, accumulation and therapeutic efficacy in
      pancreas. Moreover, the concentrations of TP-LE in heart, lung and kidney were
      lower than that of the TP group, indicating the potential for reduced toxicity of
      TP-LE. Together, all the results show that TP-LE appears to be a promising
      formulation for using TP in treating cancer, and more specifically pancreatic
      cancer. 

PMID- 25853480
TI  - Preparation of sodium cholate-based micelles through non-covalent ibonding
      interaction and application as oral delivery systems for paclitaxel.
AB  - In present study, two types of micelles based on sodium cholate (NaC) were
      prepared through non-covalent bonding interaction and the potential of micelles
      as oral drug delivery systems for paclitaxel (PTX) was evaluated. Pluronic
      chitosan (F127-CS) and Pluronic-poly (acrylic acid) (F127-PAA) copolymers were
      synthesized. Electrostatic interaction and hydrogen bond were used to prepare
      F127-CS/NaC micelles and F127-PAA/NaC micelles, respectively. The physicochemical
      characteristics of micelles were determined. An average diameter of 67.5 nm and
      unimodal pattern of size distribution were observed for F127-CS/NaC micelles.
      While for F127-PAA/NaC micelles, an average diameter of 85.89 nm and non-unimodal
      pattern of size distribution were observed. The results revealed that F127-CS/NaC
      micelles were more integrated than F127-PAA/NaC micelles. Further experiments
      showed that the F127-CS/NaC micelles had a higher drug-loading content of 12.8%
      and a lower critical micelle concentration (CMC) of 2.5 * 10-3 mol/L compared
      with F127-PAA/NaC micelles. In vitro cytotoxicity analysis demonstrated that the
      PTX-loaded F127-CS/NaC micelles were of great efficiency in inhibiting the growth
      of drug-resistant breast cancer MCF-7 cells (MCF-7/Adr). The intragastric
      administration of the PTX-loaded F127-CS/NaC micelles in rats provided a 4.33
      fold higher absolute bioavailability compared to commercial Taxol(r), indicating
      an efficient oral absorption of PTX delivered by micelles. These findings signify
      that F127-CS/NaC micelle may be a promising carrier for the delivery of PTX.

PMID- 25853481
TI  - Use of Amniotic Microparticles Coated With Fibroblasts Overexpressing SDF-1alpha
      to Create an Environment Conducive to Neovascularization for Repair of Full
      Thickness Skin Defects.
AB  - As angiogenesis and vasculogenesis involve the complex network structures of
      various types of cells, extracellular matrix components, and cytokines, it is
      still difficult to exactly mimic the microenvironment of vascularization in vivo.
      In our study, we constructed a complex containing highly proliferative
      fibroblasts that can secrete extracellular matrix components and growth factors
      to chemotaxize endothelial progenitor cells (EPCs) in an attempt to create an
      ideal microenvironment for quick vascularization. Amniotic membrane
      microparticles (mAM) rich in type IV collagen (COL IV) and laminin (LN) were
      prepared, and human dermal fibroblasts (HDF) were infected with lentivirus (LV)
      of overexpression of SDF-1alpha to construct SDF-1alpha(ov)HDF. Using the rotary
      cell culture system (RCCS), mAM was loaded with HDF or SDF-1alpha(ov)HDF to
      construct HDF-mAM and SDF-1alpha(ov)HDF-mAM complexes. The complexes were able to
      secrete various types of active peptides (IL-6, IL-8, TGF-beta, and bFGF) during
      in vitro culture. In addition, SDF-1alpha(ov)HDF-mAM complex highly expressed SDF
      1alpha. Transwell assay showed SDF-1alpha(ov)HDF-mAM complex had an apparent
      chemotactic effect on EPCs. Transplantation of complexes onto full-thickness skin
      defects of C57BL mice further demonstrated that SDF-1alpha expression and the
      number of peripheral EPCs at days 3, 5, and 7 in the SDF-1alpha(ov)HDF-mAM group
      were significantly higher than that in other groups (p < 0.01). The local
      microvascular density at day 10 of transplantation showed that the microvascular
      density in the SDF-1alpha(ov)HDF-mAM group was significantly higher than that in
      HDF-mAM group (p < 0.01). In conclusion, HDF-mAM had a strong proliferative
      activity and could be used to create a sound microenvironment for quick
      vascularization by secreting multiple cytokines and extracellular matrix
      components. Overexpression of SDF-1alpha could chemotaxize EPCs to reach local
      wounds, thus further accelerating angiogenesis in the transplant site. The
      technique described may prove to be a new model for accelerating vascularization
      of tissue and organ transplants and chronic ischemic wounds. 

PMID- 25853482
TI  - A comparison of disease burden in rheumatoid arthritis, psoriatic arthritis and
      axial spondyloarthritis.
AB  - OBJECTIVE: The main objective of this study was to compare disease burden in
      rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis
      (ax-SpA). METHODS: In this cross-sectional study, all the RA (1093), PsA (365)
      and ax-SpA (333) patients who visited the out-patient clinic of the Hospital of
      Southern Norway Trust during the year 2013 were included; the RA patients all had
      a RA diagnosis verified by the treating rheumatologist, the PsA patients all
      fulfilled the ClASsification for Psoriatic ARthritis (CASPAR) criteria and the ax
      SpA patients all fulfilled the Assessment of SpondyloArthritis international
      Society (ASAS) classification criteria for ax-SpA. Patient-reported health
      status, demographic variables, medications, and composite scores of disease
      activity were assessed. The main analyses were performed using General Linear
      Models adjusted for age, sex and multiple comparisons. Correlation analyses were
      performed using Spearman's rho. RESULTS: The reported pain, joint pain, patient's
      global assessment and fatigue were similar in PsA and ax-SpA, but significantly
      lower in RA. The 28-joint Disease Activity Score (DAS28) (0.3+/-0.1, p = 0.003),
      Clinical Disease Activity Index (CDAI) (1.0+/-0.4, p = 0.028) and Routine
      Assessment of Patient Index Data 3 (RAPID3) (0.4+/-0.1, p = 0.004) were all
      significantly higher in PsA vs. RA. RAPID3 showed moderate to high correlation
      with DAS28 (rho = 0.521, p<0.001) and CDAI (rho = 0.768, p<0.001) in RA and PsA,
      and with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (rho =
      0.902, p<0.001) and Bath Ankylosing Spondylitis Functional Index (BASFI) (0.865,
      p<0.001) in ax-SpA and PsA. CONCLUSION: In conclusion, patient- reported outcome
      measures were similar in our population of PsA and ax-SpA patients, but
      significantly lower for the RA patients. Composite disease activity measures were
      lower in RA than in PsA and ax-SpA, but the magnitude of these differences was
      small and probably not of clinical significance. Our study indicates that disease
      burden in RA, PsA and ax-SpA may be more similar than previously demonstrated.

PMID- 25853485
TI  - Supramolecular polymerization: a coarse grained molecular dynamics study.
AB  - A coarse-grained (CG) force field to model the self-assembly of benzene-1,3,5
      tricarboxamide (BTA) class of compounds in nonpolar solvents has been developed.
      The model includes an intrinsic point dipole embedded on one of the CG beads so
      as to impart a macrodipole moment to the oligomer, one of its characteristic
      feature. Chemical specificity has been preserved by benchmarking against results,
      including dimerization and solvation free energies, obtained from an all-atom
      representation. Starting from a well-dispersed configuration in n-nonane, BTA
      molecules self-assemble to form one-dimensional stacks. Free energy (FE) changes
      for the various manner in which short oligomers can exchange between the
      assembled and the dispersed states have been calculated. These calculations show
      BTA to self-assemble via a downhill cooperative mechanism with a nucleus size of
      three. 

PMID- 25853484
TI  - A suggested new bacteriophage genus, "Kp34likevirus", within the
      Autographivirinae subfamily of Podoviridae.
AB  - Klebsiella pneumoniae phages vB_KpnP_SU503 (SU503) and vB_KpnP_SU552A (SU552A)
      are virulent viruses belonging to the Autographivirinae subfamily of Podoviridae
      that infect and kill multi-resistant K. pneumoniae isolates. Phages SU503 and
      SU552A show high pairwise nucleotide identity to Klebsiella phages KP34
      (NC_013649), F19 (NC_023567) and NTUH-K2044-K1-1 (NC_025418). Bioinformatic
      analysis of these phage genomes show high conservation of gene arrangement and
      gene content, conserved catalytically active residues of their RNA polymerase, a
      common and specific lysis cassette, and form a joint cluster in phylogenetic
      analysis of their conserved genes. Also, we have performed biological
      characterization of the burst size, latent period, host specificity (together
      with KP34 and NTUH-K2044-K1-1), morphology, and structural genes as well as
      sensitivity testing to various conditions. Based on the analyses of these phages,
      the creation of a new phage genus is suggested within the Autographivirinae,
      called "Kp34likevirus" after their type phage, KP34. This genus should encompass
      the recently genome sequenced Klebsiella phages KP34, SU503, SU552A, F19 and NTUH
      K2044-K1-1.

PMID- 25853486
TI  - Anthocyanin Accumulation and Molecular Analysis of Correlated Genes in Purple
      Kohlrabi (Brassica oleracea var. gongylodes L.).
AB  - Kohlrabi (Brassica oleracea var. gongylodes L.) is an important dietary vegetable
      cultivated and consumed widely for the round swollen stem. Purple kohlrabi shows
      abundant anthocyanin accumulation in the leaf and swollen stem. Here, different
      kinds of anthocyanins were separated and identified from the purple kohlrabi
      cultivar (Kolibri) by high-performance liquid chromatography-electrospray
      ionization tandem mass spectrometry. In order to study the molecular mechanism of
      anthocyanin biosynthesis in purple kohlrabi, the expression of anthocyanin
      biosynthetic genes and regulatory genes in purple kohlrabi and a green cultivar
      (Winner) was examined by quantitative PCR. In comparison with the colorless parts
      in the two cultivars, most of the anthocyanin biosynthetic genes and two
      transcription factors were drastically upregulated in the purple tissues. To
      study the effects of light shed on the anthocyanin accumulation of kohlrabi,
      total anthocyanin contents and transcripts of associated genes were analyzed in
      sprouts of both cultivars grown under light and dark conditions. 

PMID- 25853488
TI  - Ulcerated Plaque With Lymphocutaneous Spread.

PMID- 25853487
TI  - Deep transcriptome sequencing provides new insights into the structural and
      functional organization of the wheat genome.
AB  - BACKGROUND: Because of its size, allohexaploid nature, and high repeat content,
      the bread wheat genome is a good model to study the impact of the genome
      structure on gene organization, function, and regulation. However, because of the
      lack of a reference genome sequence, such studies have long been hampered and our
      knowledge of the wheat gene space is still limited. The access to the reference
      sequence of the wheat chromosome 3B provided us with an opportunity to study the
      wheat transcriptome and its relationships to genome and gene structure at a level
      that has never been reached before. RESULTS: By combining this sequence with RNA
      seq data, we construct a fine transcriptome map of the chromosome 3B. More than
      8,800 transcription sites are identified, that are distributed throughout the
      entire chromosome. Expression level, expression breadth, alternative splicing as
      well as several structural features of genes, including transcript length, number
      of exons, and cumulative intron length are investigated. Our analysis reveals a
      non-monotonic relationship between gene expression and structure and leads to the
      hypothesis that gene structure is determined by its function, whereas gene
      expression is subject to energetic cost. Moreover, we observe a recombination
      based partitioning at the gene structure and function level. CONCLUSIONS: Our
      analysis provides new insights into the relationships between gene and genome
      structure and function. It reveals mechanisms conserved with other plant species
      as well as superimposed evolutionary forces that shaped the wheat gene space,
      likely participating in wheat adaptation.

PMID- 25853489
TI  - HIV Infection Leads to Redistribution of Leaky Claudin-2 in the Intestine of
      Humanized SCID IL-2R(-/-) Hu-PBMC Mice.

PMID- 25853490
TI  - A Bayesian model of category-specific emotional brain responses.
AB  - Understanding emotion is critical for a science of healthy and disordered brain
      function, but the neurophysiological basis of emotional experience is still
      poorly understood. We analyzed human brain activity patterns from 148 studies of
      emotion categories (2159 total participants) using a novel hierarchical Bayesian
      model. The model allowed us to classify which of five categories--fear, anger,
      disgust, sadness, or happiness--is engaged by a study with 66% accuracy (43-86%
      across categories). Analyses of the activity patterns encoded in the model
      revealed that each emotion category is associated with unique, prototypical
      patterns of activity across multiple brain systems including the cortex,
      thalamus, amygdala, and other structures. The results indicate that emotion
      categories are not contained within any one region or system, but are represented
      as configurations across multiple brain networks. The model provides a precise
      summary of the prototypical patterns for each emotion category, and demonstrates
      that a sufficient characterization of emotion categories relies on (a)
      differential patterns of involvement in neocortical systems that differ between
      humans and other species, and (b) distinctive patterns of cortical-subcortical
      interactions. Thus, these findings are incompatible with several contemporary
      theories of emotion, including those that emphasize emotion-dedicated brain
      systems and those that propose emotion is localized primarily in subcortical
      activity. They are consistent with componential and constructionist views, which
      propose that emotions are differentiated by a combination of perceptual,
      mnemonic, prospective, and motivational elements. Such brain-based models of
      emotion provide a foundation for new translational and clinical approaches.

PMID- 25853491
TI  - Parasite prevalence corresponds to host life history in a diverse assemblage of
      afrotropical birds and haemosporidian parasites.
AB  - Avian host life history traits have been hypothesized to predict rates of
      infection by haemosporidian parasites. Using molecular techniques, we tested this
      hypothesis for parasites from three haemosporidian genera (Plasmodium,
      Haemoproteus, and Leucocytozoon) collected from a diverse sampling of birds in
      northern Malawi. We found that host life history traits were significantly
      associated with parasitism rates by all three parasite genera. Nest type and nest
      location predicted infection probability for all three parasite genera, whereas
      flocking behavior is an important predictor of Plasmodium and Haemoproteus
      infection and habitat is an important predictor of Leucocytozoon infection.
      Parasite prevalence was 79.1% across all individuals sampled, higher than that
      reported for comparable studies from any other region of the world. Parasite
      diversity was also exceptionally high, with 248 parasite cytochrome b lineages
      identified from 152 host species. A large proportion of Plasmodium, Haemoproteus,
      and Leucocytozoon parasite DNA sequences identified in this study represent new,
      previously undocumented lineages (n = 201; 81% of total identified) based on
      BLAST queries against the avian malaria database, MalAvi. 

PMID- 25853492
TI  - Extremely low microsatellite diversity but distinct population structure in a
      long-lived threatened species, the Australian lungfish Neoceratodus forsteri
      (Dipnoi).
AB  - The Australian lungfish is a unique living representative of an ancient dipnoan
      lineage, listed as 'vulnerable' to extinction under Australia's Environment
      Protection and Biodiversity Conservation Act 1999. Historical accounts indicate
      this species occurred naturally in two adjacent river systems in Australia, the
      Burnett and Mary. Current day populations in other rivers are thought to have
      arisen by translocation from these source populations. Early genetic work
      detected very little variation and so had limited power to answer questions
      relevant for management including how genetic variation is partitioned within and
      among sub-populations. In this study, we use newly developed microsatellite
      markers to examine samples from the Burnett and Mary Rivers, as well as from two
      populations thought to be of translocated origin, Brisbane and North Pine. We
      test whether there is significant genetic structure among and within river
      drainages; assign putatively translocated populations to potential source
      populations; and estimate effective population sizes. Eleven polymorphic
      microsatellite loci genotyped in 218 individuals gave an average within
      population heterozygosity of 0.39 which is low relative to other threatened taxa
      and for freshwater fishes in general. Based on FST values (average over loci =
      0.11) and STRUCTURE analyses, we identify three distinct populations in the
      natural range, one in the Burnett and two distinct populations in the Mary. These
      analyses also support the hypothesis that the Mary River is the likely source of
      translocated populations in the Brisbane and North Pine rivers, which agrees with
      historical published records of a translocation event giving rise to these
      populations. We were unable to obtain bounded estimates of effective population
      size, as we have too few genotype combinations, although point estimates were
      low, ranging from 29 - 129. We recommend that, in order to preserve any local
      adaptation in the three distinct populations that they be managed separately. 

PMID- 25853494
TI  - Aflatoxin M1: Prevalence and decontamination strategies in milk and milk
      products.
AB  - Aflatoxin M1 (AFM1) in milk is among the most carcinogenic compounds, relatively
      high levels being consumed, especially by the most vulnerable age groups, i.e.
      infants and the elderly. Reports on its prevalence are constantly being received
      from various parts of the world compelling nations to establish their own
      standard limits for AFM1. Global review of the literature indicates the existence
      of methods of partial decontamination of AFM1, however; evidence based studies do
      not suggest that any single strategy as a coherent and complete solution to the
      issue. Microbial decontamination of AFM1 has emerged as the most suitable method
      up to now but the stability of toxin-microbial cell complexes still remains
      questionable. This review discusses the chemical nature, established maximum
      permissible limits and prevalence of AFM1 in various countries from 2009 to 2014.
      Moreover, the possible mechanisms for AFM1 reduction mainly the microbial
      decontamination and the stability and bioaccessibility of microbial-AFM1
      complexes are also discussed. 

PMID- 25853493
TI  - Protective role of PGC-1alpha in diabetic nephropathy is associated with the
      inhibition of ROS through mitochondrial dynamic remodeling.
AB  - The overproduction of mitochondrial reactive oxygen species (ROS) plays a key
      role in the pathogenesis of diabetic nephropathy (DN). However, the underlying
      molecular mechanism remains unclear. Our aim was to investigate the role of PGC
      1alpha in the pathogenesis of DN. Rat glomerular mesangial cells (RMCs) were
      incubated in normal or high glucose medium with or without the PGC-1alpha
      overexpressing plasmid (pcDNA3-PGC-1alpha) for 48 h. In the diabetic rats,
      decreased PGC-1alpha expression was associated with increased mitochondrial ROS
      generation in the renal cortex, increased proteinuria, glomerular hypertrophy,
      and higher glomerular 8-OHdG (a biomarker for oxidative stress). In vitro,
      hyperglycemia induced the downregulation of PGC-1alpha, which led to increased
      DRP1 expression, increased mitochondrial fragmentation and damaged network
      structure. This was associated with an increase in ROS generation and mesangial
      cell hypertrophy. These pathological changes were reversed in vitro by the
      transfection of pcDNA3-PGC-1alpha. These data suggest that PGC-1alpha may protect
      DN via the inhibition of DRP1-mediated mitochondrial dynamic remodeling and ROS
      production. These findings may assist the development of novel therapeutic
      strategies for patients with DN. 

PMID- 25853495
TI  - Pathogenic microbes manipulate cofilin activity to subvert actin cytoskeleton.
AB  - Actin-depolymerizing factor (ADF)/cofilin proteins are key players in controlling
      the temporal and spatial extent of actin dynamics, which is crucial for mediating
      host-pathogen interactions. Pathogenic microbes have evolved molecular mechanisms
      to manipulate cofilin activity to subvert the actin cytoskeletal system in host
      cells, promoting their internalization into the target cells, modifying the
      replication niche and facilitating their intracellular and intercellular
      dissemination. The study of how these pathogens exploit cofilin pathways is
      crucial for understanding infectious disease and providing potential targets for
      drug therapies. 

PMID- 25853483
TI  - The evolution of poxvirus vaccines.
AB  - After Edward Jenner established human vaccination over 200 years ago, attenuated
      poxviruses became key players to contain the deadliest virus of its own family:
      Variola virus (VARV), the causative agent of smallpox. Cowpox virus (CPXV) and
      horsepox virus (HSPV) were extensively used to this end, passaged in cattle and
      humans until the appearance of vaccinia virus (VACV), which was used in the final
      campaigns aimed to eradicate the disease, an endeavor that was accomplished by
      the World Health Organization (WHO) in 1980. Ever since, naturally evolved
      strains used for vaccination were introduced into research laboratories where
      VACV and other poxviruses with improved safety profiles were generated.
      Recombinant DNA technology along with the DNA genome features of this virus
      family allowed the generation of vaccines against heterologous diseases, and the
      specific insertion and deletion of poxvirus genes generated an even broader
      spectrum of modified viruses with new properties that increase their
      immunogenicity and safety profile as vaccine vectors. In this review, we
      highlight the evolution of poxvirus vaccines, from first generation to the
      current status, pointing out how different vaccines have emerged and approaches
      that are being followed up in the development of more rational vaccines against a
      wide range of diseases. 

PMID- 25853496
TI  - A new method of detecting pulmonary nodules with PET/CT based on an improved
      watershed algorithm.
AB  - BACKGROUND: Integrated 18F-fluorodeoxyglucose positron emission
      tomography/computed tomography (18F-FDG PET/CT) is widely performed for staging
      solitary pulmonary nodules (SPNs). However, the diagnostic efficacy of SPNs based
      on PET/CT is not optimal. Here, we propose a method of detection based on PET/CT
      that can differentiate malignant and benign SPNs with few false-positives.
      METHOD: Our proposed method combines the features of positron-emission tomography
      (PET) and computed tomography (CT). A dynamic threshold segmentation method was
      used to identify lung parenchyma in CT images and suspicious areas in PET images.
      Then, an improved watershed method was used to mark suspicious areas on the CT
      image. Next, the support vector machine (SVM) method was used to classify SPNs
      based on textural features of CT images and metabolic features of PET images to
      validate the proposed method. RESULTS: Our proposed method was more efficient
      than traditional methods and methods based on the CT or PET features alone
      (sensitivity 95.6%; average of 2.9 false positives per scan).

PMID- 25853497
TI  - Genital herpes: oral antiviral treatments.
AB  - INTRODUCTION: Genital herpes is an infection with herpes simplex virus type 1
      (HSV-1) or type 2 (HSV-2), and is among the most common sexually transmitted
      diseases. METHODS AND OUTCOMES: We conducted a systematic review and aimed to
      answer the following clinical questions: What are the effects of different oral
      antiviral treatments versus each other for a first episode of genital herpes in
      HIV-negative people? What are the effects of different antiviral treatments for
      genital herpes in HIV-positive people? We searched: Medline, Embase, The Cochrane
      Library, and other important databases up to October 2013 (Clinical Evidence
      reviews are updated periodically; please check our website for the most up-to
      date version of this review). We included harms alerts from relevant
      organisations such as the US Food and Drug Administration (FDA) and the UK
      Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found
      eight studies that met our inclusion criteria. We performed a GRADE evaluation of
      the quality of evidence for interventions. CONCLUSIONS: In this systematic review
      we present information relating to the effectiveness and safety of the following
      interventions: aciclovir, famciclovir, and valaciclovir.

PMID- 25853499
TI  - Rapid and simple preparation of remarkably stable binary nanoparticle planet
      satellite assemblies.
AB  - We demonstrate a straightforward nonbiomolecular approach for self-assembly of
      binary NP planet-satellite superstructures, which display remarkable colloidal
      and structural stability under variations in temperature, pH, ionic strength and
      solvent. The readily scalable process produces highly homogeneous samples and is
      tolerant to variations in building block size and shape, giving rapid access to a
      structurally diverse range of robust binary NP assemblies. 

PMID- 25853498
TI  - A PHF8 homolog in C. elegans promotes DNA repair via homologous recombination.
AB  - PHF8 is a JmjC domain-containing histone demethylase, defects in which are
      associated with X-linked mental retardation. In this study, we examined the roles
      of two PHF8 homologs, JMJD-1.1 and JMJD-1.2, in the model organism C. elegans in
      response to DNA damage. A deletion mutation in either of the genes led to
      hypersensitivity to interstrand DNA crosslinks (ICLs), while only mutation of
      jmjd-1.1 resulted in hypersensitivity to double-strand DNA breaks (DSBs). In
      response to ICLs, JMJD-1.1 did not affect the focus formation of FCD-2, a homolog
      of FANCD2, a key protein in the Fanconi anemia pathway. However, the dynamic
      behavior of RPA-1 and RAD-51 was affected by the mutation: the accumulations of
      both proteins at ICLs appeared normal, but their subsequent disappearance was
      retarded, suggesting that later steps of homologous recombination were defective.
      Similar changes in the dynamic behavior of RPA-1 and RAD-51 were seen in response
      to DSBs, supporting a role of JMJD-1.1 in homologous recombination. Such a role
      was also supported by our finding that the hypersensitivity of jmjd-1.1 worms to
      ICLs was rescued by knockdown of lig-4, a homolog of Ligase 4 active in
      nonhomologous end-joining. The hypersensitivity of jmjd-1.1 worms to ICLs was
      increased by rad-54 knockdown, suggesting that JMJD-1.1 acts in parallel with RAD
      54 in modulating chromatin structure. Indeed, the level of histone H3 Lys9 tri
      methylation, a marker of heterochromatin, was higher in jmjd-1.1 cells than in
      wild-type cells. We conclude that the histone demethylase JMJD-1.1 influences
      homologous recombination either by relaxing heterochromatin structure or by
      indirectly regulating the expression of multiple genes affecting DNA repair. 

PMID- 25853500
TI  - A New Mechanism in Electrochemical Process for Arsenic Oxidation: Production of
      H2O2 from Anodic O2 Reduction on the Cathode under Automatically Developed
      Alkaline Conditions.
AB  - Electrochemical cathodes are often used to reduce contaminants or produce
      oxidizing substances (i.e., H2O2). Alkaline conditions develop automatically
      around the cathode in electrochemical processes, and O2 diffuses onto the cathode
      easily. However, limited attention is paid to contaminant transformation by the
      reactive species produced on the cathode under oxic and alkaline conditions due
      to the inapplicability of pH for Fenton reaction. In this study, a new oxidation
      mechanism on the cathode is presented for contaminant transformation under
      automatically developed alkaline conditions. In an electrochemical sand column,
      6.67 MUM As(III) was oxidized by 36% when it passed through the cathode under the
      conditions of 30 mA current, an initial pH of 7.5 and a flow rate of 2 mL/min.
      Under the alkaline conditions (pH 10.0-11.0) that developed automatically around
      the cathode, the reduction potential of As(III) decreased greatly, allowing a
      pronounced oxidation by the small quantities of H2O2 produced from O2 reduction
      on the cathode. As(III) oxidation was further increased by the presence of soil
      pore water and groundwater solutes of HCO3-, Ca2+, Mg2+ and humic acid. The new
      oxidation mechanism found for the cathode under localized alkaline conditions
      supplements the fundamentals of contaminant transformation in electrochemical
      processes.

PMID- 25853501
TI  - A Ferric-Peroxo Intermediate in the Oxidation of Heme by IsdI.
AB  - The canonical heme oxygenases (HOs) catalyze heme oxidation via a heme-bound
      hydroperoxo intermediate that is stabilized by a water cluster at the active site
      of the enzyme. In contrast, the hydrophobic active site of IsdI, a heme-degrading
      enzyme from Staphylococcus aureus, lacks a water cluster and is expected to
      oxidize heme by an alternative mechanism. Reaction of the IsdI-heme complex with
      either H2O2 or m-chloroperoxybenzoic acid fails to produce a specific oxidized
      heme iron intermediate, suggesting that ferric-hydroperoxo or ferryl derivatives
      of IsdI are not involved in the catalytic mechanism of this enzyme. IsdI lacks a
      proton-donating group in the distal heme pocket, so the possible involvement of a
      ferric-peroxo intermediate has been evaluated. Density functional theory (DFT)
      calculations indicate that heme oxidation involving a ferric-peroxo intermediate
      is energetically accessible, whereas the energy barrier for a reaction involving
      a ferric-hydroperoxo intermediate is too great in the absence of a proton donor.
      We propose that IsdI catalyzes heme oxidation through nucleophilic attack by the
      heme-bound peroxo species. This proposal is consistent with our previous
      demonstration by nuclear magnetic resonance spectroscopy that heme ruffling
      increases the susceptibility of the meso-carbon of heme to nucleophilic attack. 

PMID- 25853503
TI  - Orbital Mucormycosis Following Periorbital Cutaneous Infection.
AB  - Mucormycosis is an aggressive fungal infection characterized by rapidly
      progressive angioinvasion and tissue necrosis. When present in the orbit,
      mucormycosis can quickly lead to permanent visual loss and potentially fatal
      cerebral extension. Orbital involvement is almost universally preceded by
      infection of the paranasal sinuses. Secondary infection of the orbit via direct
      extension of neighboring cutaneous mucormycosis has not been previously
      described. The authors present a case of cutaneous mucormycosis with orbital
      extension in a poorly controlled diabetic patient.

PMID- 25853502
TI  - Gambogic acid induces apoptosis in diffuse large B-cell lymphoma cells via
      inducing proteasome inhibition.
AB  - Resistance to chemotherapy is a great challenge to improving the survival of
      patients with diffuse large B-cell lymphoma (DLBCL), especially those with
      activated B-cell-like DLBCL (ABC-DLBCL). Therefore it is urgent to search for
      novel agents for the treatment of DLBCL. Gambogic acid (GA), a small molecule
      derived from Chinese herb gamboges, has been approved for Phase II clinical trial
      for cancer therapy by Chinese FDA. In the present study, we investigated the
      effect of GA on cell survival and apoptosis in DLBCL cells including both GCB-
      and ABC-DLBCL cells. We found that GA induced growth inhibition and apoptosis of
      both GCB- and ABC-DLBCL cells in vitro and in vivo, which is associated with
      proteasome malfunction. These findings provide significant pre-clinical evidence
      for potential usage of GA in DLBCL therapy particularly in ABC-DLBCL treatment. 

PMID- 25853504
TI  - Granulocytic Sarcoma of the Orbit Presenting as a Fulminant Orbitopathy in an
      Adult With Acute Myeloid Leukemia.
AB  - A 64-year-old woman with relapsed acute myelogenous leukemia (AML) undergoing
      salvage chemotherapy developed rapid onset of right-sided ophthalmoplegia,
      proptosis, optic neuropathy, and vision loss from 20/30 to hand motions over a 3
      hour period on day 4 of her treatment. CT scan of her orbits revealed a
      superolateral orbital mass and periocular edema. She underwent immediate
      canthotomy and cantholysis, and lateral orbitotomy with debulking of the mass
      later the same day. The histopathology was consistent with aggregates of myeloid
      blasts. Her vision recovered to 20/20 on postoperative day 1. Orbital
      granulocytic sarcoma is a rare condition often concurrent with AML, typically in
      the pediatric population and rarely in adults. Presentation as a fulminant
      orbitopathy with rapidly progressive optic neuropathy and vision loss over
      several hours has not been previously reported.

PMID- 25853505
TI  - Topical Imiquimod in the Treatment of Conjunctival Actinic Keratosis.
AB  - Conjunctival actinic keratosis is rare and difficult to treat, as recurrences are
      common. Imiquimod, an immune response modulator, is currently Food and Drug
      Administration-approved for cutaneous actinic keratosis and superficial basal
      cell carcinomas. Emerging reports have shown it to be effective in treating some
      periocular and conjunctival lesions. The authors present a case of a 68-year-old
      white man with recurrent actinic keratosis involving the pretarsal conjunctiva,
      which was successfully treated with 5% topical imiquimod following previous
      failure with cryotherapy and interferon alpha-2b. The patient had ocular
      irritation that resolved on cessation of treatment. To the authors' knowledge,
      this is the first report of conjunctival actinic keratosis being treated with and
      successfully eradicated by topical imiquimod.

PMID- 25853506
TI  - Diode Laser-Assisted Endocanalicular Dacryocystorhinostomy: A Prospective Study.
AB  - PURPOSE: To evaluate the efficacy of the diode laser in endocanalicular
      dacryocystorhinostomy. METHODS: A prospective, noncomparative, interventional
      case series using the diode laser for endocanalicular dacryocystorhinostomy in
      patients with tearing and nasolacrimal duct obstruction. Outcome measures
      included subjective tearing complaints and objective patency of the nasolacrimal
      system. Success was defined as improvement of symptoms with patency of
      nasolacrimal drainage. Patients were followed for 12 months. Institutional review
      board approval was obtained. RESULTS: Forty eyes (28 unilateral, 6 bilateral)
      underwent surgery. Five cases were excluded because of inadequate follow-up.
      Patients ranged in age from 27 to 88 years (66.7 +/- 15.7). Seventy-seven percent
      were female and 23% were male. At 1 week, 88% had improvement in tearing, 12% had
      no change or worsening of symptoms, and all patients were patent on irrigation.
      At 1 month, 86% had improvement, 14% had no change, and all patients were patent
      on irrigation. At 3 months, 83% had improvement and were patent on irrigation.
      Seventeen percent had no change or worsening with reflux and were considered
      failures. At 6 months, 77% had improvement and were patent on irrigation. Five
      additional patients had no change, reflux on exam and were failed surgeries. At
      12 months, 74% had complete resolution and were patent. One additional patient
      failed. Nine surgeries in 35 cases were considered failures by 12 months.
      CONCLUSIONS: Subjective complaints of tearing correlated with patency of the
      nasolacrimal system after 3 months. A success rate of 74.3% (26 out of 35 cases)
      was observed by 12 months.

PMID- 25853507
TI  - The Quantitated Internal Suture Browpexy: Comparison of Two Brow-Lifting
      Techniques in Patients Undergoing Upper Blepharoplasty.
AB  - PURPOSE: To describe and evaluate 1) the quantitated internal suture browpexy
      (ISB), which combines the advantages of a browpexy and "brassiere suture," 2) the
      endoscopic Endotine browplasty, and 3) to compare these two techniques in
      patients undergoing simultaneous upper blepharoplasty. METHODS: Retrospective
      review of patients undergoing bilateral upper blepharoplasty alone, bilateral ISB
      with upper blepharoplasty, and bilateral Endotine (MicroAire, Charlottesville,
      VA, U.S.A.) browplasty with upper blepharoplasty by one surgeon was performed.
      ImageJ 1.47v software (Wayne Rasband, National Institutes of Health, Bethesda,
      MD, U.S.A.) and standardized photographs were used to measure pre- and
      postoperative brow position at three positions (central, medial, lateral).
      Statistical analysis was performed using Sigmaplot version 12.5 for Windows
      (Systat Software, Inc., San Jose, CA, U.S.A.). RESULTS: Thirty-three patients
      undergoing ISB with blepharoplasty, 33 undergoing Endotine browplasty with
      blepharoplasty, and 30 patients undergoing blepharoplasty alone were included.
      The 3 groups were matched for age and gender. Patients undergoing upper
      blepharoplasty alone showed statistically significant brow descent at all three
      brow positions (mean: -1.7 mm [p <= 0.04]). The quantitated ISB prevented brow
      descent but provided minimal brow elevation (mean lateral elevation: right eye
      (OD) +1.3 mm [p = 0.03]; OS +0.9 mm [p = 0.08]). Endotine browplasty with upper
      blepharoplasty provided significant brow elevation at all brow positions,
      particularly laterally (OD +4.0 mm [p < 0.001]; OS +3.5 mm [p < 0.001]). There
      were no complications. CONCLUSIONS: Upper blepharoplasty alone is associated with
      brow descent; performing ISB simultaneously effectively prevents this descent.
      Endotine browplasty with upper blepharoplasty achieves significant brow
      elevation. Quantitation of the browpexy allows reproducible placement of the
      suture thereby producing consistent and symmetrical results.

PMID- 25853508
TI  - C5-azobenzene-functionalized locked nucleic acid uridine: isomerization
      properties, hybridization ability, and enzymatic stability.
AB  - Oligonucleotides (ONs) modified with a locked nucleic acid (LNA) are widely used
      in the fields of therapeutics, diagnosis, and nanotechnology. There have been
      significant efforts towards developing LNA analogues bearing modified bridges to
      improve their hybridization ability, nuclease resistance, and pharmacokinetic
      profiles. Moreover, nucleobase modifications of LNA are useful strategies for the
      functionalization of ONs. Modifications of the C5-position of pyrimidine
      nucleobases are particularly interesting because they enable predictable
      positioning of functional groups in the major groove of the duplex. Here we
      report the synthesis of C5-azobenzene-functionalized LNA uridine (LNA-U(Az)) and
      properties of LNA-U(Az)-modified ONs, including isomerization properties,
      hybridization ability, and enzyme stability. LNA-U(Az) in ON is photo-isomerized
      effectively and reversibly by irradiation at 365 nm (trans to cis) and 450 nm
      (cis to trans). LNA-U(Az)-modified ONs show RNA-selective hybridization ability
      despite the large hydrophobic azobenzene moiety extending into the major groove
      of the duplex. The enzymatic stability of LNA-U(Az)-modified ONs is higher than
      that of natural and LNA-modified ONs with or without photo-irradiation. Our
      results indicate that LNA-U(Az) holds promise for RNA targeting and photo
      switchable technologies.

PMID- 25853509
TI  - Therapeutic effects of topical netrin-4 inhibits corneal neovascularization in
      alkali-burn rats.
AB  - Netrins are secreted molecules involved in axon guidance and angiogenesis.
      However, the role of netrins in the vasculature remains unclear. Netrin-4 and
      netrin-1 have been found to be either pro- or antiangiogenic factors. Previously,
      we found that netrin-1 acts as an anti-angiogenic factor in rats by inhibiting
      alkali burn-induced corneal neovascularization. Here, we further investigate the
      effects of netrin-4, another member of the same netrin family, on
      neovascularization in vitro and in vivo. We found that netrin-4 functions
      similarly as netrin-1 in angiogenesis. In vitro angiogenesis assay shows that
      netrin-4 affected human umbilical vein endothelial cell (HUVEC) tube formation,
      viability and proliferation, apoptosis, migration, and invasion in a dose
      dependent manner. Netrin-4 was topically applied in vivo to alkali-burned rat
      corneas on day 0 (immediately after injury) and/or day 10 post-injury. Netrin-4
      subsequently suppressed and reversed corneal neovascularization. Netrin-4
      inhibited corneal epithelial and stromal cell apoptosis, inhibited vascular
      endothelial growth factor (VEGF), but promoted pigment epithelium-derived factor
      (PEDF) expression, decreased NK-KB p65 expression, and inhibits neutrophil and
      macrophage infiltration. These results indicate that netrin-4 shed new light on
      its potential roles in treatmenting for angiogenic diseases that affect the
      ocular surface, as well as other tissues. 

PMID- 25853510
TI  - Expectant parents' understanding of the implications and management of fever in
      the neonate.
AB  - OBJECTIVE: We estimated the extent to which Canadian expectant parents would seek
      medical care in a febrile neonate (age 30 days or less). We also evaluated
      expectant parents' knowledge of signs and symptoms of fever in a neonate, and
      explored the actions Canadian expectant parents would take to optimize the health
      of their child. METHODS: We conducted a cross-sectional survey of a sample of
      expectant parents from a large urban center in Canada. We recruited participants
      from waiting rooms in an obstetrical ultrasound clinic located in an urban
      tertiary care hospital in Montreal, Canada. We asked participants nine questions
      about fever in neonates including if, and how, they would seek care for their
      neonate if they suspected he/she were febrile. RESULTS: Among the 355
      respondents, (response rate 87%) we found that 75% of parents reported that they
      would take their febrile neonate for immediate medical assessment, with nearly
      one fifth of the sample reporting that they would not seek medical care. We found
      no significant associations between the choice to seek medical care and expectant
      parents socio-demographic characteristics. CONCLUSIONS: Despite universal access
      to high quality health care in Canada, our study highlights concerning gaps in
      the knowledge of the care of the febrile infant in one fifth of expectant
      parents. Physicians and health providers should strive to provide early education
      to expectant parents about how to recognize signs of fever in the neonate and how
      best to seek medical care. This may improve neonatal health outcomes in Canada.

PMID- 25853511
TI  - The Maternal and Child Health (MCH) handbook in Mongolia: a cluster-randomized,
      controlled trial.
AB  - OBJECTIVE: To assess the effectiveness of the Maternal and Child Health (MCH)
      handbook in Mongolia to increase antenatal clinic attendance, and to enhance
      health-seeking behaviors and other health outcomes. METHODS: A cluster randomized
      trial was conducted using the translated MCH handbook in Bulgan, Mongolia to
      assess its effectiveness in promoting antenatal care attendance. Pregnant women
      were recruited from 18 randomly allocated districts using shuffled, sealed
      envelopes. The handbook was implemented immediately for women at their first
      antenatal visit in the intervention group, and nine months later in the control
      group. The primary outcome was the number of antenatal care visits of all women
      residing in the selected districts. Cluster effects were adjusted for using
      generalized estimation equation. Masking was not possible among care providers,
      pregnant women and assessors. FINDINGS: Nine districts were allocated to the
      intervention group and the remainder to the control group. The intervention group
      (253 women) attended antenatal clinics on average 6*9 times, while the control
      group (248 women) attended 6*2 times. Socioeconomic status affected the frequency
      of clinic attendance: women of higher socioeconomic status visited antenatal
      clinics more often. Pregnancy complications were more likely to be detected among
      women using the handbook. CONCLUSION: The MCH handbook promotes continuous care
      and showed an increase in antenatal visits among the intervention group. The
      intervention will help to identify maternal morbidities during pregnancy and
      promote health-seeking behaviors. TRIAL REGISTRATION: UMIN Clinical Trial
      Registry UMIN000001748.

PMID- 25853512
TI  - Tribenzodecacyclene and hexabenzodecacyclene.
AB  - High-temperature, TiCl4-catalyzed, triple aldol condensations of aceanthrenone 5
      and acenaphthacenone 6 gave tribenzodecacyclene 3 and hexabenzodecacyclene 4,
      respectively, in yields of 16 and 0.8%, respectively. Compound 3 is a red,
      crystalline solid that is stable under ordinary conditions; its X-ray structure
      reveals it to be a strongly pitched, C3-symmetric, molecular propeller. In
      contrast, the more highly strained compound 4 is a blue-black solid whose
      solutions are unstable to air and light. Its simple NMR spectra, as well as HDFT
      calculations, indicate that it is a D3-symmetric molecular propeller. 

PMID- 25853513
TI  - Comparative analysis of cystatin superfamily in platyhelminths.
AB  - The cystatin superfamily is comprised of cysteine proteinase inhibitors and
      encompasses at least 3 subfamilies: stefins, cystatins and kininogens. In this
      study, the platyhelminth cystatin superfamily was identified and grouped into
      stefin and cystatin subfamilies. The conserved domain of stefins (G, QxVxG) was
      observed in all members of platyhelminth stefins. The three characteristics of
      cystatins, the cystatin-like domain (G, QxVxG, PW), a signal peptide, and one or
      two conserved disulfide bonds, were observed in platyhelminths, with the
      exception of cestodes, which lacked the conserved disulfide bond. However, it is
      noteworthy that cestode cystatins had two tandem repeated domains, although the
      second tandem repeated domain did not contain a cystatin-like domain, which has
      not been previously reported. Tertiary structure analysis of Taenia solium
      cystatin, one of the cestode cystatins, demonstrated that the N-terminus of T.
      solium cystatin formed a five turn alpha-helix, a five stranded beta-pleated
      sheet and a hydrophobic edge, similar to the structure of chicken cystatin.
      Although no conserved disulfide bond was found in T. solium cystatin, the models
      of T. solium cystatin and chicken cystatin corresponded at the site of the first
      disulfide bridge of the chicken cystatin. However, the two models were not
      similar regarding the location of the second disulfide bridge of chicken
      cystatin. These results showed that T. solium cystatin and chicken cystatin had
      similarities and differences, suggesting that the biochemistry of T. solium
      cystatin could be similar to chicken cystatin in its inhibitory function and that
      it may have further functional roles. The same results were obtained for other
      cestode cystatins. Phylogenetic analysis showed that cestode cystatins
      constituted an independent clade and implied that cestode cystatins should be
      considered to have formed a new clade during evolution. 

PMID- 25853514
TI  - Lucy Montoro Rehabilitation Network mobile unit: an alternative public healthcare
      policy.
AB  - PURPOSE: The aim is to analyze rehabilitation services provided by a mobile
      rehabilitation clinic (MU) in nine regions of the State of Sao Paulo,
      demonstrating the distribution of orthoses, prostheses and other mobility aids
      for persons with physical disabilities according to age groups and impairments,
      as well as the number of persons with physical disabilities as estimated by
      Brazilian official data sources. METHOD: The number of persons with disabilities
      in each region was obtained through estimations from the 2010 Brazilian IBGE
      Census. The number of assistive technologies suppliers and technicians were
      provided by the Brazilian Technical Orthopedics Association (ABOTEC). Patients
      were referred to the MU by Regional Health Departments. After examination of a
      multidisciplinary team, assistive devices are prescribed and delivered according
      to patients' needs. Data on patients were also assessed according to
      questionnaires on their age, diagnosis, gender, marital status and education
      level. RESULTS: From 2009 to 2011, the MU went through 15,000 km providing
      rehabilitation services through the Public Health System to 1801 patients.
      Additionally, 3328 devices were delivered in this period. Different age,
      diagnosis, gender, marital status and schooling profiles are highlighted in each
      of the analyzed regions. CONCLUSION: Data on patients' profiles were made
      available through services provided by the MU--including the average index of
      1.85 devices delivered to each patient and demand projections--which can be used
      in the planning of public policies. The MU made rehabilitation services more
      accessible, trained professionals, raised awareness on the correct delivery and
      use of assistive devices, and identified and organized people's demand in each
      region. Implications for Rehabilitation Delivering prostheses, orthoses and other
      mobility aids fulfills the rights of persons with disabilities to personal
      mobility with the greatest possible independence, as foreseen by the Convention
      on the Rights of Persons with Disabilities, increasing their participation in
      society on an equal basis with others. The direct impact of actively reaching out
      into the community to provide quality rehabilitation services and assistive
      devices increases the level of access of persons with disabilities to health
      services and equalizes opportunities. Outreach initiatives to deliver
      rehabilitation services in the community must include a capacity-building
      component. Building the capacities of local practitioners and health personnel
      will further empower both these professionals and persons with disabilities,
      diminishing attitudinal barriers. Reaching out into the community allows
      gathering data on the prevalence of health conditions, local need and demand for
      assistive devices and rehabilitation services, and informs decision-making.

PMID- 25853515
TI  - Functional genomics screening utilizing mutant mouse embryonic stem cells
      identifies novel radiation-response genes.
AB  - Elucidating the genetic determinants of radiation response is crucial to
      optimizing and individualizing radiotherapy for cancer patients. In order to
      identify genes that are involved in enhanced sensitivity or resistance to
      radiation, a library of stable mutant murine embryonic stem cells (ESCs), each
      with a defined mutation, was screened for cell viability and gene expression in
      response to radiation exposure. We focused on a cancer-relevant subset of over
      500 mutant ESC lines. We identified 13 genes; 7 genes that have been previously
      implicated in radiation response and 6 other genes that have never been
      implicated in radiation response. After screening, proteomic analysis showed
      enrichment for genes involved in cellular component disassembly (e.g. Dstn and
      Pex14) and regulation of growth (e.g. Adnp2, Epc1, and Ing4). Overall, the best
      targets with the highest potential for sensitizing cancer cells to radiation were
      Dstn and Map2k6, and the best targets for enhancing resistance to radiation were
      Iqgap and Vcan. Hence, we provide compelling evidence that screening mutant ESCs
      is a powerful approach to identify genes that alter radiation response.
      Ultimately, this knowledge can be used to define genetic variants or therapeutic
      targets that will enhance clinical therapy. 

PMID- 25853516
TI  - Prevalence of asthma and allergic rhinitis among adults in Yaounde, Cameroon.
AB  - BACKGROUND: Population-based estimates of asthma and allergic rhinitis in sub
      Saharan African adults are lacking. We assessed the prevalence and determinants
      of asthma and allergic rhinitis in urban adult Cameroonians. METHODS: A community
      based survey was conducted from December 2013 to April 2014 among adults aged 19
      years and above (N = 2,304, 57.3% women), selected through multilevel stratified
      random sampling across all districts of Yaounde (Capital city). Internationally
      validated questionnaires were used to investigate the presence of allergic
      diseases. Logistic regressions were employed to investigate the determinants of
      allergic conditions. RESULTS: Prevalence rates were 2.7% (95% CI: 2.1-3.4) for
      asthma-ever, 6.9% (5.9-7.9) for lifetime wheezing, 2.9% (92.2-3.6) for current
      wheezing and 11.4% (10.1-12.7) for self-reported lifetime allergic rhinitis;
      while 240 (10.4%) participants reported current symptoms of allergic rhinitis,
      and 125 (5.4%) had allergic rhino-conjunctivitis. The prevalence of current
      asthma medication use and self-reported asthma attack was 0.8 (0.4-1.2) and 1
      (0.6-1.4) respectively. Multivariable adjusted determinants of current wheezing
      were signs of atopic eczema [2.91 (1.09-7.74)] and signs of allergic rhinitis
      [3.24 (1.83-5.71)]. Age group 31-40 years [0.27(0.09-0.78), p = 0.016] was an
      independent protective factor for wheezing. Determinants of current rhinitis
      symptoms were active smoking [2.20 (1.37-3.54), p<0.001], signs of atopic eczema
      [2.84 (1.48-5.46)] and current wheezing [3.02 (1.70-5.39)]. CONCLUSION:
      Prevalence rates for asthma and allergic rhinitis among adults in this population
      were at the lower tails of those reported in other regions of the world. Beside
      the classical interrelation between allergic diseases found in this study, active
      smoking was an independent determinant of allergic rhinitis symptoms. Nationwide
      surveys are needed to investigate regional variations.

PMID- 25853517
TI  - Phosphine resistance in India is characterised by a dihydrolipoamide
      dehydrogenase variant that is otherwise unobserved in eukaryotes.
AB  - Phosphine (PH3) fumigation is the primary method worldwide for controlling insect
      pests of stored commodities. Over-reliance on phosphine, however, has led to the
      emergence of strong resistance. Detailed genetic studies previously identified
      two loci, rph1 and rph2, that interact synergistically to create a strong
      resistance phenotype. We compared the genetics of phosphine resistance in strains
      of Rhyzopertha dominica and Tribolium castaneum from India and Australia,
      countries having similar pest species but widely differing in pest management
      practices. Sequencing analysis of the rph2 locus, dihydrolipoamide dehydrogenase
      (dld), identified two structurally equivalent variants, Proline49>Serine (P49S)
      in one R. dominica strain and P45S in three strains of T. castaneum from India.
      These variants of the DLD protein likely affect FAD cofactor interaction with the
      enzyme. A survey of insects from storage facilities across southern India
      revealed that the P45/49S variant is distributed throughout the region at very
      high frequencies, in up to 94% of R. dominica and 97% of T. castaneum in the
      state of Tamil Nadu. The abundance of the P45/49S variant in insect populations
      contrasted sharply with the evolutionary record in which the variant was absent
      from eukaryotic DLD sequences. This suggests that the variant is unlikely to
      provide a strong selective advantage in the absence of phosphine fumigation. 

PMID- 25853518
TI  - Chromosomal patterns of diversity and differentiation in creepers: a next-gen
      phylogeographic investigation of Certhia americana.
AB  - With methods for sequencing thousands of loci for many individuals,
      phylogeographic studies have increased inferential power and the potential for
      applications to new questions. In songbirds, strong patterns of inter-chromosomal
      synteny, the published genome of a songbird and the ability to obtain thousands
      of genetic loci for many individuals permit the investigation of differentiation
      between and diversity within lineages across chromosomes. Here, we investigate
      patterns of differentiation and diversity in Certhia americana, a widespread
      North American songbird, using next-generation sequencing. Additionally, we
      reassess previous phylogeographic studies within the group. Based on ~30 million
      sequencing reads and more than 16,000 single-nucleotide polymorphisms in 41
      individuals, we identified a strong positive relationship between genetic
      differentiation and chromosome size, with a negative relationship between genetic
      diversity and chromosome size. A combination of selection and drift may explain
      these patterns, although we found no evidence for selection. Because the observed
      genomic patterns are very similar between widespread, allopatric clades, it is
      unlikely that selective pressures would be so similar across such different
      ecological conditions. Alternatively, the accumulation of fixed differences
      between lineages and loss of genetic variation within lineages due to genetic
      drift alone may explain the observed patterns. Due to relatively higher
      recombination rates on smaller chromosomes, larger chromosomes would, on average,
      accumulate fixed differences between lineages and lose genetic variation within
      lineages faster, leading to the patterns observed here in C. americana.

PMID- 25853519
TI  - Incidence of type 2 diabetes in pre-diabetic Japanese individuals categorized by
      HbA1c levels: a historical cohort study.
AB  - OBJECTIVE: Reported incidence of type 2 diabetes estimated at the pre-diabetic
      stage differs widely (2.3-18.1% per year). Because clinicians need to know the
      risk of incident diabetes after a diagnosis of pre-diabetes, our objective was to
      estimate precise incidence of diabetes using baseline HbA1c levels. METHODS: A
      historical cohort study using electronic medical record data obtained between
      January 2008 and December 2013. A total of 52,781 individuals with HbA1c < 6.5%
      were assigned to one of six groups categorized by baseline HbA1c level: <= 5.5%
      (n=34,616), 5.6-5.7% (n=9,388), 5.8-5.9% (n=4,664), 6.0-6.1% (n= 2,338), 6.2-6.3%
      (n=1,257), and 6.4% (n=518). Participants were tracked until a subsequent
      diagnosis of diabetes or end of follow-up during a period of 5 years. RESULTS:
      During the follow-up period (mean 3.7 years), 4,369 participants developed
      diabetes. The incidence of diabetes in the first year was 0.7, 1.5, 2.9, 9.2,
      30.4, and 44.0% in the six HbA1c groups, respectively. At five years the
      incidence was 3.6, 8.9, 13.8, 27.5, 51.6, and 67.8%, respectively (p < 0.0001
      comparing the HbA1c <=5.5% group to the other groups). After adjustment for
      confounding factors, the hazard ratios compared with the HbA1c <=5.5% group were
      significantly elevated: 2.3 (95%CI 2.0-2.5), 3.4 (95%CI 2.9-3.7), 8.8 (95%CI 8.0
      10.1), 26.3 (95%CI 23.3-30.1), and 48.7 (95%CI 40.8-58.1) in the five HbA1c
      groups (p < 0.0001). CONCLUSION: By fractionating baseline HbA1c levels into
      narrower HbA1c range groups, accuracy of estimating the incidence of type 2
      diabetes in subsequent years was increased. The risk of developing diabetes
      increased with increasing HbA1c levels, especially with the HbA1c level >= 6.2%
      in the first follow-up year.

PMID- 25853520
TI  - Economic behavior under the influence of alcohol: an experiment on time
      preferences, risk-taking, and altruism.
AB  - We report results from an incentivized laboratory experiment undertaken with the
      purpose of providing controlled evidence on the causal effects of alcohol
      consumption on risk-taking, time preferences and altruism. Our design
      disentangles the pharmacological effects of alcohol intoxication from those
      mediated by expectations, as we compare the behavior of three groups of subjects:
      those who participated in an experiment with no reference to alcohol, those who
      were exposed to the possibility of consuming alcohol but were given a placebo and
      those who effectively consumed alcohol. All subjects participated in a series of
      economic tasks administered in the same sequence across treatments. After
      controlling for both the willingness to pay for an object and the potential
      misperception of probabilities as elicited in the experiment, we detect no effect
      of alcohol in depleting subjects' risk tolerance. However, we find that alcohol
      intoxication increases impatience and makes subjects less altruistic. 

PMID- 25853522
TI  - The effect of lentiviral vector-mediated RNA interference targeting hypoxia
      inducible factor 1alpha on the uptake of fluorodeoxyglucose ((18)f) in the human
      pancreatic cancer cell line, patu8988.
AB  - Hypoxia can stimulate (18)F-fluorodeoxyglucose ((18)F-FDG) uptake in cultured
      tumor cells. This study has investigated the effect of lentiviral vector-mediated
      RNA interference (RNAi) targeting hypoxia-inducible factor 1alpha (HIF-1alpha) on
      the changes in HIF-1 and glucose transporter 1 (Glut-1) expression, the cell
      growth, and the uptake of (18)F-FDG in the human pancreatic cancer cell line,
      Patu8988. Lentiviral RNAi vector targeting the HIF-1alpha gene (LV-HIF
      1alphaRNAi) was constructed and used to treat cells at various concentrations (25
      200 nM). The expression changes of HIF-1alpha and Glut-1 in hypoxic Patu8988
      cells after RNAi treatment were determined using real time reverse transcription
      polymerase chain reaction (real-time PCR). The inhibition rate of cell
      proliferation 48 hours after the addition of 10 MUL of different concentrations
      of LV-HIF-1alphaRNAi (25-200 nM) was assayed using the MTT method. Meanwhile, the
      cell uptake of (18)F-FDG was also assessed. After RNAi transfection, the relative
      expression levels of HIF-1alpha mRNA and Glut-1 under hypoxia were reduced and
      the relative expression levels of HIF-1alpha protein also decreased. Compared
      with the control group, the inhibition rates of cell proliferation under
      different viral dosages were 5.98%, 15.65%, 26.42%, and 40.81%, respectively,
      positively correlated with the viral doses (r=0.558, p<0.05). Under hypoxia, Glut
      1 mRNA expression in Patu8988 cells treated with 200 nM of LV-HIF-1alphaRNAi for
      24, 48, and 72 hours, respectively, was positively correlated with the inhibition
      rate of cell proliferation (r=0.618, p<0.05) as well as the inhibition rate of
      (18)F-FDG uptake (r=0.664, p<0.05), while the latter two displayed a positive
      correlation with each other too (r=0.582, p<0.05). Under hypoxia, RNAi targeting
      HIF-1alpha significantly inhibited the expression of Glut-1 mRNA in Patu8988
      pancreatic cancer cells and their uptake of (18)F-FDG. These results suggest that
      LV-HIF-1alphaRNAi may form a new treatment for pancreatic cancer, and the
      effectiveness of the treatment can be readily assessed with (18)F-FDG imaging. 

PMID- 25853523
TI  - Serotonin's many meanings elude simple theories.

PMID- 25853521
TI  - Coxsackievirus A16 elicits incomplete autophagy involving the mTOR and ERK
      pathways.
AB  - Autophagy is an important homeostatic process for the degradation of cytosolic
      proteins and organelles and has been reported to play an important role in
      cellular responses to pathogens and virus replication. However, the role of
      autophagy in Coxsackievirus A16 (CA16) infection and pathogenesis remains
      unknown. Here, we demonstrated that CA16 infection enhanced autophagosome
      formation, resulting in increased extracellular virus production. Moreover,
      expression of CA16 nonstructural proteins 2C and 3C was sufficient to trigger
      autophagosome accumulation by blocking the fusion of autophagosomes with
      lysosomes. Interestingly, we found that Immunity-related GTPase family M (IRGM)
      was crucial for the activation of CA16 infection-induced autophagy; in turn,
      reducing IRGM expression suppressed autophagy. Expression of viral protein 2C
      enhanced IRGM promoter activation, thereby increasing IRGM expression and
      inducing autophagy. CA16 infection inhibited Akt/mTOR signaling and activated
      extracellular signal-regulated kinase (ERK) signaling, both of which are
      necessary for autophagy induction. In summary, CA16 can use autophagy to enhance
      its own replication. These results raise the possibility of targeting the
      autophagic pathway for the treatment of hand, foot, and mouth disease (HFMD). 

PMID- 25853524
TI  - Plasma Kallikrein Inhibitors in Cardiovascular Disease: An Innovative Therapeutic
      Approach.
AB  - Plasma prekallikrein is the liver-derived precursor of the trypsin-like serine
      protease plasma kallikrein, and circulates in plasma bound to high molecular
      weight kininogen. Plasma prekallikrein is activated to plasma kallikrein by
      activated factor XII or prolylcarboxypeptidase. Plasma kallikrein regulates the
      activity of multiple proteolytic cascades in the cardiovascular system such as
      the intrinsic pathway of coagulation, the kallikrein-kinin system, the
      fibrinolytic system, the renin-angiotensin system, and the complement pathways.
      As such, plasma kallikrein plays a central role in the pathogenesis of
      thrombosis, inflammation, and blood pressure regulation. Under physiological
      conditions, plasma kallikrein serves as a cardioprotective enzyme. However, its
      increased plasma concentration or hyperactivity perpetuates cardiovascular
      disease (CVD). In this article, we review the biochemistry and cell biology of
      plasma kallikrein and summarize data from preclinical and clinical studies that
      have established important functions of this serine protease in CVD states.
      Finally, we propose plasma kallikrein inhibitors as a novel class of drugs with
      potential therapeutic applications in the treatment of CVDs. 

PMID- 25853526
TI  - Income disparity and student career choice.

PMID- 25853527
TI  - Family medicine resident billing and lost revenue: a regional cross-sectional
      study.
AB  - BACKGROUND AND OBJECTIVES: The financial margins for primary care clinics and
      residencies are narrow. It is important that residents bill properly for
      educational and financial purposes as well as for compliance. This study compares
      resident and attending Evaluation and Management (E&M) coding from family
      medicine residency programs across a five-state region, with established billing
      benchmarks. METHODS: We collected established visit E&M codes for faculty and
      residents from a network of family medicine residencies in the Northwest United
      States over a 6-month period. Aggregated codes were compared to billing
      benchmarks from the Medical Group Management Association (MGMA) to estimate
      effects on revenue from these visits. RESULTS: We obtained coding data for
      131,788 established problem-focused visits from 353 residents and 186 faculty
      physicians in 16 of 18 eligible family medicine residencies. Both residents and
      faculty billed lower numbers of high complexity codes than MGMA benchmarks. PGY
      1s coded higher numbers of high complexity codes than PGY-3s. Annual estimated
      revenue loss was $481,654 for the programs overall. CONCLUSIONS: Residents do not
      bill established visits at the level of generally accepted benchmarks, which
      contributes to significant financial losses for programs and carries regulatory
      implications. The reasons for incorrect billing need to be established and
      interventions developed to overcome these barriers.

PMID- 25853525
TI  - Epileptogenic but MRI-normal perituberal tissue in Tuberous Sclerosis Complex
      contains tuber-specific abnormalities.
AB  - INTRODUCTION: Recent evidence has implicated perituberal, MRI-normal brain tissue
      as a possible source of seizures in tuberous sclerosis complex (TSC). Data on
      aberrant structural features in this area that may predispose to the initiation
      or progression of seizures are very limited. We used immunohistochemistry and
      confocal microscopy to compare epileptogenic, perituberal, MRI-normal tissue with
      cortical tubers. RESULTS: In every sample of epileptogenic, perituberal tissue,
      we found many abnormal cell types, including giant cells and cytomegalic neurons.
      The majority of giant cells were surrounded by morphologically abnormal
      astrocytes with long processes typical of interlaminar astrocytes. Perituberal
      giant cells and astrocytes together formed characteristic "microtubers". A
      parallel analysis of tubers showed that many contained astrocytes with features
      of both protoplasmic and gliotic cells. CONCLUSIONS: Microtubers represent a
      novel pathognomonic finding in TSC and may represent an elementary unit of
      cortical tubers. Microtubers and cytomegalic neurons in perituberal parenchyma
      may serve as the source of seizures in TSC and provide potential targets for
      therapeutic and surgical interventions in TSC.

PMID- 25853528
TI  - Beyond diagnoses: family medicine core themes in student reflective writing.
AB  - BACKGROUND AND OBJECTIVES: We share qualitative study results of third-year
      medical student writings during their family medicine clerkship utilizing a
      reflective writing exercise from 2005 and 2013. METHODS: For this paper, 50
      student writings were randomly selected from the 2005 cohort in addition to 50
      student writings completed by the 2013 cohort. Deductive thematic analysis
      utilizing Atlas.ti software was completed utilizing the Future of Family Medicine
      core attributes of family physicians as the a priori coding template. RESULTS:
      Student writings actively reflect key attributes of family physicians as
      described by the Future of Family Medicine Report: a deep understanding of the
      dynamics of the whole person, a generative impact on patients' lives, a talent
      for humanizing the health care experience, and a natural command of complexity
      and multidimensional access to care. CONCLUSIONS: We discuss how to lead the
      writing exercise and provide suggestions for facilitating the discussion to bring
      out these important aspects of family medicine care.

PMID- 25853529
TI  - Are nonphysician health care providers prepared and supported to teach in family
      medicine?
AB  - BACKGROUND AND OBJECTIVES: Understanding how nonphysician health care providers
      (NPHCPs) teach medical trainees is integral to optimizing family medicine
      education. The objective of this study was to examine the teaching roles, level
      of preparation and support, and the challenges encountered by NPHCPs. METHODS: A
      cross-sectional web-based survey of NPHCPs was conducted across academic teaching
      units affiliated with the University of Toronto's Department of Family and
      Community Medicine (DFCM). The level of preparation for educational roles,
      perceived support, challenges encountered, and educational training needs of
      NPHCPs were examined. Variables associated with preparedness to teach were also
      identified. RESULTS: Of the 193 NPHCPs surveyed, 166 (86%) completed the
      questionnaire. A total of 126 (82%) of NPHCP educators (nurses, social workers,
      dietitians, and pharmacists) reported teaching medical trainees. Most did not
      hold faculty appointments. The majority had no formal training in teaching, and
      less than half felt prepared for their academic responsibilities. NPHCPs
      perceived a lack of support for their teaching. NPHCPs also identified
      predictable challenges such as lack of time and lack of funding. Challenges
      specific to cross-professional teaching were also identified. NPHCPs expressed an
      interest in receiving continuing education to improve their teaching skills.
      NPHCPs' self-reported level of preparedness to teach was variable and associated
      with years of teaching experience, information received about trainees,
      challenges faced, and continuing education needs. CONCLUSIONS: NPHCPs are
      extensively involved in teaching medical trainees. There is variability in their
      preparation level, and they encounter significant challenges. To advance
      effective and sustainable inter-professional education (IPE) within family
      medicine, addressing these issues is crucial.

PMID- 25853530
TI  - Personality profiles of rural longitudinal integrated clerkship students who
      choose family medicine.
AB  - BACKGROUND AND OBJECTIVES: Physician workforce projections fuel interest in
      addressing the shortage of family physicians. Copious research has investigated
      personality as a variable influencing specialty intention. Medical school rural
      longitudinal integrated clerkships (LICs) nurture interest in family medicine.
      This study examined whether rural LIC students who intended to and eventually
      matched into family medicine portrayed a personality trait profile different from
      rural LIC students who intended or matched to all other specialities. The
      profiles of four successive cohorts are described in relation to their intended
      and eventual specialty match. METHODS: A cross-sectional design sampled 145 third
      year students from 2008--2011. A survey measured demographics, temperament and
      character personality traits, and Other-Oriented Empathy. Multivariate analysis
      compared family medicine versus all other specialty matches and original
      specialty intention with eventual match. RESULTS: Match groups did not differ in
      gender, age, or marital status. Rural LIC students who matched in family medicine
      had lower levels of Harm Avoidance, higher Reward Dependence, and nonsignificant
      higher levels of every other personality trait in comparison to other matches.
      Rural LIC students who intended and matched to family medicine showed the highest
      levels of Reward Dependence (warm sociability) and Other-Oriented Empathy
      compared to any other specialty. CONCLUSIONS: Lower levels of Harm Avoidance are
      conducive to less anxiety, more composure and confidence in making decisions, and
      being relaxed in accepting a degree of risk and uncertainty. Such calm optimism
      along with higher Reward Dependence showing social warmth and empathy are
      desirable traits for family physicians regularly confronted with a wide range of
      presentations from the obvious to complex. Further investigation of what
      influences sustainability of the intention to enter family medicine may be useful
      to educators for counseling.

PMID- 25853531
TI  - Microblog use and student engagement in the large-classroom setting.
AB  - BACKGROUND AND OBJECTIVES: Encouraging student engagement in the large-classroom
      setting can be difficult. Challenges include the depersonalized nature of the
      environment and the fact that students frequently find asking questions and
      participating in class discussion intimidating. Social media has the potential to
      address these barriers, but this has not yet been formally evaluated. Our study
      analyzed the impact of microblog use on students' question-asking behaviors (an
      indicator of student engagement) in a large-classroom setting. METHODS: Formative
      evaluation of a large-classroom medical humanities course identified microblog
      use as a potential tool to facilitate greater student engagement. A microblog was
      thereafter incorporated into the course. Student engagement was operationalized
      as question-asking behaviors before and after microblog incorporation. RESULTS:
      Paired t tests showed that the total number of questions asked was significantly
      greater in the microblog-available classes, t (2)=12.12. In addition,
      significantly more individual students asked questions in the microblog-available
      classes, t (2)=17.39. CONCLUSIONS: Our study, demonstrating an increase in
      question-asking behavior after incorporation of a microblog, has important
      implications for educators who seek to enhance student engagement and learning in
      the large-classroom setting. In addition, innovative use of emerging technologies
      (such as microblogs) as educational tools requires continuous assessment and
      iterative change to maximize benefit. More research is needed to evaluate what
      specific barriers to engagement are overcome by microblog use and whether
      microblog use can similarly benefit other courses.

PMID- 25853532
TI  - What providers want from the Primary Care Extension Service to facilitate
      practice transformation.
AB  - BACKGROUND AND OBJECTIVES: While several experts have shared their visions of the
      Primary Care Extension Service (PCES) as called for in the Affordable Care Act
      (ACA), little is known about providers' perspective. We aimed to identify the
      most and least desired resources that primary care providers want from the PCES.
      METHODS: A 70-question survey was administered to primary care providers (n=556)
      in Pennsylvania, one of four initial states chosen to develop the PCES
      infrastructure. Analysis focused on the highest and lowest ranked questions.
      RESULTS: The most desired PCES services include (1) identifying and coordinating
      mental health services, (2) improving office efficiency, (3) increasing overall
      revenues, and (4) strategies to help implement evidence-based clinical
      guidelines. The least desired PCES services include (1) implementing e
      prescribing, (2) implementing an electronic medical record (EMR) system, (3)
      implementing group visits, (4) recruiting new patients, and (5) implementing open
      or advanced access scheduling. CONCLUSIONS: Despite expert models presented for
      the PCES, there is a critical need to ask primary care providers what they need
      from such a service. Our findings identified some divergences from key patient
      centered medical home (PCMH) components, including the low ranking of services
      related to EMRs and increasing patient access. With interest growing in
      developing a PCES that would help spread innovation as outlined in the ACA, it's
      important to take a demand-side approach to the services providers most desire
      versus the more traditional supply-side approach that assumes the assistance
      providers need.

PMID- 25853533
TI  - Newborn well-child visits in the home setting: a pilot study in a family medicine
      residency.
AB  - BACKGROUND: The purpose of our study was to pilot a home visit program targeting
      neonates conducted by family medicine residents. While the literature shows that
      home visit programs are successful at preventing adverse outcomes for young
      children, such as improving parenting practices and promoting breastfeeding, no
      data exist about newborn home visits conducted by resident physicians. METHODS:
      Residents conducted newborn home visits precepted by a family medicine faculty
      member from June 2012--May 2013. Subjects were recruited from the residency
      continuity practice and randomized to receive two home visits (which replaced two
      office visits) or routine office-based newborn care. All participants were
      surveyed using the validated WHOQOL-BREF quality of life scale and a patient
      satisfaction instrument. Metrics were also obtained from the electronic medical
      record. Mothers and resident physicians completed an open-ended questionnaire
      about their experience. RESULTS: All patients, whether receiving office-based or
      home-based care, rated their care highly. Significant differences were seen in
      usage of acute care in the first 6 months of life, and mothers in the home visit
      group trended toward initiating breastfeeding at a higher rate. The home visit
      group ranked their quality of life higher across all domains when compared to the
      control group, approaching statistical significance in two domains. Residents
      providing home visits reported increased connectedness to patients and improved
      confidence in anticipatory guidance delivery. CONCLUSIONS: Home visits are
      valuable for families with newborns, in terms of minimizing acute care service
      usage, breastfeeding promotion, and perhaps increasing maternal perceptions of
      well-being. A home visit program has the potential to enhance resident education
      and the doctor-patient relationship.

PMID- 25853534
TI  - Social media beliefs and usage among family medicine residents and practicing
      family physicians.
AB  - BACKGROUND AND OBJECTIVES: Incorporation of social media (SM) use in medicine is
      gaining support. The Internet is now a popular medium for people to solicit
      medical information. Usage of social networks, such as Facebook and Twitter, is
      growing daily and provides physicians with nearly instantaneous access to large
      populations for both marketing and patient education. The benefits are myriad,
      but so are the inherent risks. We investigated the role providers' age and
      medical experience played in their beliefs and use of SM in medicine. METHODS:
      Using multiple state-wide and national databases, we assessed social media use by
      family medicine residents, faculty, and practicing family physicians with a 24
      question online survey. Descriptive data is compared by age and level of medical
      experience. RESULTS: A total of 61 family medicine residents and 192 practicing
      family physicians responded. There is a trend toward higher SM utilization in the
      younger cohort, with 90% of resident respondents reporting using SM, half of them
      daily. A total of 64% of family physician respondents over the age of 45 have a
      SM account. An equal percentage of senior physicians use SM daily or not at all.
      Practicing physicians, more than residents, agree that SM can be beneficial in
      patient care. The vast majority of residents and physicians polled believe that
      SM should be taught early in medical education. CONCLUSIONS: The high utilization
      of SM by younger providers, high prevalence of patient use of the Internet, and
      the countless beneficial opportunities SM offers should be catalysts to drive
      curriculum development and early implementation in medical education. This
      curriculum should focus around four pillars: professional standards for SM use,
      SM clinical practice integration, professional networking, and research.

PMID- 25853535
TI  - Students do not reduce patient satisfaction in a family medicine clinic as
      measured by a nationally used patient satisfaction instrument.
AB  - BACKGROUND AND OBJECTIVES: Patient satisfaction surveys are widely used to give
      physicians feedback on their treatment of patients, included in physician
      performance evaluation and payment, and correlated with better health outcomes.
      Our research uses industry-standard satisfaction measures to gauge the impact on
      patient satisfaction of having students involved in a patient's medical care at
      the family medicine clinic of a large southwestern osteopathic medical school.
      METHODS: A retrospective cohort study was conducted using the Press-Ganey Survey,
      a national survey commonly used by hospitals and clinics. The survey was modified
      to indicate the presence of a learner in the patient's treatment room. The survey
      provided data on patient satisfaction with the office, the visit, and the care
      received. RESULTS: Overall, 730 survey responses were used in the study, 434 from
      patients with whose visit included a student. There were no statistically
      significant differences in patient satisfaction scores, including overall
      satisfaction with the visit. CONCLUSIONS: Our findings indicate that student
      doctors do not decrease patient satisfaction and that satisfaction scores may be
      useful in student evaluations. This finding should encourage outpatient
      physicians who teach medical students that their patient satisfaction scores on
      the most widely used patient satisfaction survey will not be impacted by teaching
      students.

PMID- 25853536
TI  - Time to change our paradigm for faculty recruitment; old rules are failing us: we
      need to recruit new faculty before they graduate.

PMID- 25853538
TI  - Updating indicators for scaling the socioeconomic level of families for health
      research.
AB  - BACKGROUND: Socioeconomic position is a community-used concept in health
      research. The social level is related to numerous exposures, resources, and
      susceptibilities that may affect health. AIM: To update and validate a tool for
      scaling the socioeconomic level of families for health research. PARTICIPANTS AND
      METHODS: A multistage stratified cluster sampling technique was used to select
      900 families (one index person per family) from urban and rural areas in the
      Alexandria governorate using the proportional allocation method. Ten variables
      reflecting parental education, parental occupation, family characteristics,
      financial status as well as home sanitation were reduced to a single
      socioeconomic status (SES) index using two methods: the Sigma scoring method and
      factor analysis. Reliability and validity were assessed for the developed scale.
      Factor scores were classified into three categories (low, medium, high) using
      cluster analysis, and then different cut-off points for the Sigma scoring method
      were used and compared with the cluster solution using the kappa statistic.
      RESULTS: Results showed that the developed scale was both reliable (Cronbach's
      alpha coefficient alpha=0.79) and valid [8 out of the 10 items had high loading
      (>0.5) for SES]. The best cut-off points for SES classification using the
      proposed scoring system that yielded the highest agreement with the cluster
      solution (kappa=0.77) were less than 40%, 40 to <70%, and at 70% or more, with an
      overall correct classification of 84.7%. CONCLUSION AND RECOMMENDATION: The new
      scale proved to be valid and reliable. This scale is recommended for use for
      scaling the socioeconomic level of families for health research.

PMID- 25853537
TI  - Dual Emission of a Novel (P,N) Re(I) Complex: A Computational and Experimental
      Study on [P,N-{(C6H5)2(C5H4N)P}Re(CO)3Br].
AB  - The spectroscopic, electrochemical, and photophysical properties of the new
      complex [P,N-{(C6H5)2(C5H4N)P}Re(CO)3Br] are reported. The UV-vis spectrum in
      dichloromethane shows an absorption maximum centered at 315 nm and a shoulder at
      350 nm. These absorption bands have been characterized to have MLCT character.
      Excitation at both wavelengths (maximum and shoulder) leads to an emission band
      centered at 550 nm. Cyclic voltammetry experiments show two ill-defined
      irreversible oxidation waves around +1.50 and 1.80 V that are assigned to
      Re(I)/Re(II) and Re(II)/Re(III) couples whereas an irreversible reduction signal
      centered at -1.80 V is likewise assigned to a ligand reduction process. These
      results support the proposal of the MLCT nature of the states implied by the
      emission of the complex. The luminescent decay fits to a biexponential function,
      where the lifetimes and emission quantum yields are dependent on the solvent
      polarity. DFT calculations suggest that dpi -> pi*pyridine and dpi -> pi*phenyl
      excited states may account for the existence of two decay lifetimes. 

PMID- 25853539
TI  - Effects of a training program about breast cancer and breast self-examination
      among female students at Taif University.
AB  - BACKGROUND: Breast cancer is the most common type of cancer in Saudi women. It is
      spreading three times faster in the Kingdom than in other countries. One-third of
      breast cancers are preventable through healthy life styles. OBJECTIVE: This study
      aimed to assess the impact of a training program on breast cancer and breast self
      examination (BSE) among female students at Taif University. PARTICIPANTS AND
      METHODS: This study was carried out using a pre-post test design on a sample of
      female university students from seven colleges in Taif University (Faculty of
      Science, Faculty of Economics and Management, Faculty of Art, Faculty of
      Education, Faculty of Medicine, Faculty of Pharmacy, and the Faculty of Applied
      Medical Sciences) in the academic year 2012-2013. RESULTS: None of the
      participants had ever practiced BSE before training, and only 16% of them
      believed that BSE is necessary, whereas 8.7% were willing to teach others BSE.
      There was limited knowledge of breast cancer. After the training program, a
      significant improvement was observed in all knowledge items, and 83.6% of the
      students practiced BSE compared with 0% practice before training. CONCLUSION:
      This study showed the effectiveness of the intervention program in improving
      students' knowledge of breast cancer and their practice of BSE. Thus, campaigns
      focusing on females in this age group should be carried out in the Saudi society.

PMID- 25853540
TI  - Factors associated with health-related quality of life among patients with liver
      cirrhosis in Egypt.
AB  - BACKGROUND: Although the disease burden of liver cirrhosis in Egypt is high and
      there are few resources for its management, there is limited research on the
      health-related quality of life (HRQOL) of Egyptian patients with liver cirrhosis.
      AIMS: To describe the HRQOL of liver cirrhotic patients in Egypt and to analyse
      factors associated with this construct. PATIENTS AND METHODS: A cross-sectional
      study with a convenience sample of 401 patients from three hospitals in Cairo,
      Egypt, was carried out in June-August 2011. Patients were interviewed to complete
      a background data form, Short Form-36, the Liver Disease Symptom Index-2.0 and
      the Multidimensional Scale of Perceived Social Support. RESULTS: Patients had low
      HRQOL, with mental health perceived to be poorer than physical health. In
      regression analyses, severity of symptoms, disease stage, comorbidities and
      employment status were associated significantly with physical health, accounting
      for 19% of the variance. For mental health, 31.7% of the variation was explained
      by severity of symptoms, employment status and perceived spouse and family
      support. CONCLUSION AND RECOMMENDATIONS: These findings highlight the needs of
      patients with liver cirrhosis in Egypt. Engaging the patients' family in care
      planning may decrease patients' burden and improve their HRQOL. This study also
      provides a rationale to develop future research in symptom management to enhance
      HRQOL.

PMID- 25853541
TI  - Interleukin-4 -590 T>C and interleukin-4 receptor Q551R A>G gene polymorphisms in
      Saudi cases with alopecia areata.
AB  - OBJECTIVES: Immunogenetic factors are known to play a role in the pathogenesis of
      alopecia areata (AA). This study aimed at investigating the association between
      AA with the polymorphisms of interleukin-4 (IL-4) promoter and receptor (IL-4R)
      genes. PATIENTS AND METHODS: This work is a case-control study that was conducted
      on 76 AA patients from Qassim region, Saudi Arabia. Patients were compared with
      93 normal healthy controls from the same locality. Genomic DNA was extracted and
      processed using real-time PCR amplification for characterization of IL-4 -590 T>C
      and IL-4R Q551R A>G gene polymorphisms. RESULTS: Cases of AA showed a higher
      frequency of the IL-4 -590 CC homozygous genotype compared with controls (63.2
      vs. 53.8%, P>0.05) with a lower frequency of the TT genotype (5.3 vs. 10.8%);
      yet, both were statistically nonsignificant (P>0.05). Regarding the IL-4R Q551R
      A>G polymorphism, cases and controls showed nearly equal frequencies of all
      variants, that is, with no significant difference. Although the frequency of the
      IL-4 C and the IL-4R A alleles was higher among cases than among controls (78.9
      vs. 71.5% and 78.8 vs. 72.6%, respectively), this was also statistically
      nonsignificant (P>0.05). Comparing case subgroups in terms of their age of onset,
      sex, disease severity, consanguinity, and family history showed no statistically
      significant difference regarding the studied genetic variant. CONCLUSION: IL-4 
      590 and IL-4R Q551R gene polymorphisms are not associated with the susceptibility
      and the clinical pattern of AA in Saudi patients. We recommend further research
      studies involving the estimation of cytokines both in the serum and in the local
      skin lesions or in cultured skin cells to figure out whether Th1 or Th2 pathways
      play a specific role in the pathogenesis of AA.

PMID- 25853542
TI  - Predictors of drug resistance in tuberculosis patients in the Eastern Province,
      Saudi Arabia.
AB  - BACKGROUND: Management of patients with drug-resistant tuberculosis is highly
      complicated because of the longer treatment time, lesser effectiveness of second
      line antituberculosis drugs, more side-effects, and a significant financial
      burden on tuberculosis control programs. This study aimed to identify predictors
      of drug-resistant tuberculosis. MATERIALS AND METHODS: It was a case-control
      record study conducted in an antituberculosis center in a government hospital in
      the Eastern Province of Saudi Arabia. Cases were pulmonary tuberculosis patients
      with antituberculosis drug resistance (n=80), and controls were pulmonary
      tuberculosis patients without drug resistance (n=101). Data were collected from
      patients' records during the period from January 2008 to February 2013. RESULTS:
      Male sex [odds ratio (OR)=5.764; 95% confidence interval (CI) 2.024-16.421],
      smoking (OR=4.605; 95% CI 1.864-11.378), and positive Acid Fast Bacilli smear on
      admission (OR=40.149; 95% CI 9.010-178.914) were the risk factors for developing
      drug resistance (P<0.05 for each) in the sample. CONCLUSION AND RECOMMENDATIONS:
      Positive AFB smear on admission, male sex, and smoking are risk factors for
      developing drug-resistant TB. These predictors should be used to formulate a
      health policy to monitor tuberculosis patients so as to prevent drug resistance.

PMID- 25853543
TI  - Health-promoting lifestyle behaviors among nurses in private hospitals in Al
      Khobar, Saudi Arabia.
AB  - BACKGROUND: An individual's lifestyle influences health, and health-promoting
      behaviors and a healthy lifestyle are crucial means to maintain health. Nurses
      play a significant role as models in health-promoting activities. OBJECTIVE: The
      aim of this study was to describe the current health-promoting lifestyle of
      nurses in private hospitals and investigate possible associations between health
      behaviors and demographic characteristics. PARTICIPANTS AND METHODS: This was a
      cross-sectional study. A total of 420 nurses were assessed using the Health
      Promotion Lifestyle Profile (HPLP-II) scale as a self-administered questionnaire.
      RESULTS: The mean age of about 78% women and 22% men was 33.12+/-8.52 years. Most
      of them (98%) were non-Saudi, and 50% had a diploma; 38% had 5-10 years of
      experience, 50% were married, 49% had children, and 64% had a monthly income of
      less than 3000 Saudi Riyal. 'Spiritual growth' showed the highest mean score and
      'physical activity' showed the lowest mean score. Significant differences in
      nurses' health-promoting lifestyle behaviors and significant correlations were
      found between the HPLP-II and demographic variables. CONCLUSION: Nurses' display
      of health responsibility, nutrition, interpersonal relations, and stress
      management behaviors was moderate. Although their physical activity was low,
      their spiritual growth was high. For older, married, and those nurses whose
      monthly income was more than 3000 Saudi Riyal, the nutrition score was higher.
      Age, marital, and economic status were associated significantly with nutritional
      health behavior. RECOMMENDATION: Development and training programs should be
      performed to raise awareness of the importance of health education and health
      promotion, and the necessary facilities should be provided at the work place to
      encourage healthy behavior.

PMID- 25853544
TI  - Prevalence of cardiovascular disease risk factors among Egyptian and Saudi
      medical students: a comparative study.
AB  - BACKGROUND: Results from recent reports suggest that the mortality and the
      morbidity from coronary heart disease (CHD) is leveling, especially in younger
      adults. Studies conducted in both Saudi Arabia and Egypt, aiming at the
      estimation of the prevalence of cardiovascular risk factors among the young
      population, demonstrated a high prevalence of risk factors. OBJECTIVE: The aim of
      this study was to compare the prevalence of cardiovascular risk factors among
      medical students aged 18-25 years in two Middle East countries (Egypt and Saudi
      Arabia). PARTICIPANTS AND METHODS: This was a cross-sectional comparative study
      involving a sample of 360 medical students of both sexes randomly selected from
      students enrolled into two medical colleges in Saudi Arabia and Egypt. RESULTS:
      The prevalence of risk factors for cardiovascular disease was relatively high
      among both Saudi and Egyptian medical students, particularly a sedentary life
      style, obesity, and abdominal obesity. Smoking was practiced by 29.7% of both
      populations. A significantly higher prevalence of obesity and a reported family
      history of premature CHD were observed among the Saudi students and a
      significantly higher prevalence of hypertension was found among male Egyptian
      students as compared with male Saudi students. A relatively high proportion of
      both populations (23.9% of Saudi students and 16.7% of the Egyptian students) was
      at an increased risk of developing fatal cardiovascular disease within 10 years.
      CONCLUSION: Apart from the higher prevalence of obesity and reported family
      history of premature CHD among the Saudi students and the significantly higher
      prevalence of hypertension among the Egyptian students, there was no
      statistically significant difference between the risk profiles of both
      populations. Participatory behavior change programs in medical schools for the
      adoption of healthy lifestyles, particularly involvement in regular physical
      activity and smoking cessation are highly recommended.

PMID- 25853545
TI  - Mild ammonium stress increases chlorophyll content in Arabidopsis thaliana.
AB  - Nitrate (NO3(-)) and ammonium (NH4(+)) are the main forms of nitrogen available
      in the soil for plants. Excessive NH4(+) accumulation in tissues is toxic for
      plants and exclusive NH4(+)-based nutrition enhances this effect. Ammonium
      toxicity syndrome commonly includes growth impairment, ion imbalance and
      chlorosis among others. In this work, we observed high intraspecific variability
      in chlorophyll content in 47 Arabidopsis thaliana natural accessions grown under
      1 mM NH4(+) or 1 mM NO3(-) as N-source. Interestingly, chlorophyll content
      increased in every accession upon ammonium nutrition. Moreover, this increase was
      independent of ammonium tolerance capacity. Thus, chlorosis seems to be an
      exclusive effect of severe ammonium toxicity while mild ammonium stress induces
      chlorophyll accumulation. 

PMID- 25853546
TI  - Vertically-aligned carbon nanotubes on aluminum as a light-weight positive
      electrode for lithium-polysulfide batteries.
AB  - A light-weight, high specific surface current collector made of vertically
      aligned carbon nanotubes grown on an aluminum substrate was fabricated and
      studied as a positive electrode in a semi-liquid lithium/polysulfide battery.
      This simple system delivered stable capacities over 1000 mA h gS(-1) and 2 mA h
      cm(-2) with almost no capacity loss over 50 cycles. 

PMID- 25853547
TI  - Orientated Guidance of Peripheral Nerve Regeneration Using Conduits with a
      Microtube Array Sheet (MTAS).
AB  - Material surface topography has been shown to affect the biological behavior of
      cells in vitro; however, the in vivo effect on peripheral nerve regeneration has
      not been explored. Here, we studied the potential of a microtube array sheet
      (MTAS) with a unique longitudinal surface topography to promote peripheral nerve
      regeneration efficiency, both in vivo and in vitro. Schwann cells, spinal cord
      motor neurons, and dorsal root ganglion neurons were seeded on the MTAS to study
      the effect of the construct on the biological properties and behaviors of neural
      cells. The MTAS guided the oriented migration of Schwann cells without affecting
      other critical biological properties, such as proliferation and neurotrophin
      expression. In addition, the MTAS guided the directed extension of neurites from
      both types of neurons. Next, we tested the capability of the MTAS to facilitate
      peripheral nerve regeneration by bridging a 10 mm sciatic nerve defect in rats
      with a nerve conduit equipped with an MTAS lining. The MTAS significantly
      promoted peripheral nerve regeneration, as suggested by the greater fiber caliber
      in the midconduit and the greater abundance of fibers in nerve segment distal to
      the conduit. Moreover, scanning electron microscopy (SEM) analysis suggested the
      orientated guidance of nerve regeneration by the MTAS, as indicated by the
      smaller eccentricity of the nerve fibers and the concordant arrangement of the
      collagen fiber in both the fibers and the matrix in the MTAS group. Our results
      collectively suggest that the conduits with the MTAS developed in this study have
      significant potential for facilitating peripheral nerve regeneration by modifying
      critical biological behaviors and guiding orientated nerve growth. 

PMID- 25853548
TI  - Aptamer-conjugated polymeric nanoparticles for the detection of cancer cells
      through "turn-on" retro-self-quenched fluorescence.
AB  - We have developed a simple, sensitive, and rapid fluorescence assay for the
      detection of cancer cells, based on "turn-on" retro-self-quenched fluorescence
      inside the cells. 1,3-Phenylenediamine resin (DAR) nanoparticles (NPs) containing
      rhodamine 6G (R6G) are conjugated with aptamer (apt) sgc8c to prepare sgc8c
      R6GDAR NPs, while that containing rhodamine 101 (R101) are conjugated with TD05
      for the preparation of TD05-R101DAR NPs. The sgc8c-R6GDAR and TD05-R101DAR NPs
      separately recognize CCRF-CEM and Ramos cells. The fluorescence intensities of
      the two apt-DAR NPs are both weak due to self-quenching, but they increase inside
      the cells as a result of release of the fluorophores from the apt-DAR NPs. The
      apt-DAR NPs' structure becomes less compact at low pH value, leading to the
      release of the fluorophores. The sgc8c-R6GDAR and TD05-R101DAR NPs allow
      detection of as low as 44 CCRF-CEM cells and 79 Ramos cells mL(-1), respectively,
      using a commercial reader within 10 min. Practicality of the two probes have been
      validated by the quantitation and identification of CCRF-CEM and Ramos cells
      spiked in blood samples through conventional fluorescence and flow cytometry
      analysis, with advantages of sensitivity, selectivity, and rapidity. 

PMID- 25853549
TI  - Detection of mitochondrial COII DNA sequences in ant guts as a method for
      assessing termite predation by ants.
AB  - Termites and ants contribute more to animal biomass in tropical rain forests than
      any other single group and perform vital ecosystem functions. Although ants prey
      on termites, at the community level the linkage between these groups is poorly
      understood. Thus, assessing the distribution and specificity of ant termitophagy
      is of considerable interest. We describe an approach for quantifying ant-termite
      food webs by sequencing termite DNA (cytochrome c oxidase subunit II, COII) from
      ant guts and apply this to a soil-dwelling ant community from tropical rain
      forest in Gabon. We extracted DNA from 215 ants from 15 species. Of these, 17.2 %
      of individuals had termite DNA in their guts, with BLAST analysis confirming the
      identity of 34.1 % of these termites to family level or better. Although ant
      species varied in detection of termite DNA, ranging from 63 % (5/7; Camponotus
      sp. 1) to 0 % (0/7; Ponera sp. 1), there was no evidence (with small sample
      sizes) for heterogeneity in termite consumption across ant taxa, and no evidence
      for species-specific ant-termite predation. In all three ant species with
      identifiable termite DNA in multiple individuals, multiple termite species were
      represented. Furthermore, the two termite species that were detected on multiple
      occasions in ant guts were in both cases found in multiple ant species,
      suggesting that ant-termite food webs are not strongly compartmentalised.
      However, two ant species were found to consume only Anoplotermes-group termites,
      indicating possible predatory specialisation at a higher taxonomic level. Using a
      laboratory feeding test, we were able to detect termite COII sequences in ant
      guts up to 2 h after feeding, indicating that our method only detects recent
      feeding events. Our data provide tentative support for the hypothesis that
      unspecialised termite predation by ants is widespread and highlight the use of
      molecular approaches for future studies of ant-termite food webs. 

PMID- 25853550
TI  - Characterization of the immunophenotypes and antigenomes of colorectal cancers
      reveals distinct tumor escape mechanisms and novel targets for immunotherapy.
AB  - BACKGROUND: While large-scale cancer genomic projects are comprehensively
      characterizing the mutational spectrum of various cancers, so far little
      attention has been devoted to either define the antigenicity of these mutations
      or to characterize the immune responses they elicit. Here we present a strategy
      to characterize the immunophenotypes and the antigen-ome of human colorectal
      cancer. RESULTS: We apply our strategy to a large colorectal cancer cohort (n =
      598) and show that subpopulations of tumor-infiltrating lymphocytes are
      associated with distinct molecular phenotypes. The characterization of the
      antigenome shows that a large number of cancer-germline antigens are expressed in
      all patients. In contrast, neo-antigens are rarely shared between patients,
      indicating that cancer vaccination requires individualized strategy. Analysis of
      the genetic basis of the tumors reveals distinct tumor escape mechanisms for the
      patient subgroups. Hypermutated tumors are depleted of immunosuppressive cells
      and show upregulation of immunoinhibitory molecules. Non-hypermutated tumors are
      enriched with immunosuppressive cells, and the expression of immunoinhibitors and
      MHC molecules is downregulated. Reconstruction of the interaction network of
      tumor-infiltrating lymphocytes and immunomodulatory molecules followed by a
      validation with 11 independent cohorts (n = 1,945) identifies BCMA as a novel
      druggable target. Finally, linear regression modeling identifies major
      determinants of tumor immunogenicity, which include well-characterized modulators
      as well as a novel candidate, CCR8, which is then tested in an orthologous
      immunodeficient mouse model. CONCLUSIONS: The immunophenotypes of the tumors and
      the cancer antigenome remain widely unexplored, and our findings represent a step
      toward the development of personalized cancer immunotherapies.

PMID- 25853552
TI  - Increased isolation frequency of toxigenic Vibrio cholerae O1 from environmental
      monitoring sites in Haiti.
AB  - Since the identification of the first cholera case in 2010, the disease has
      spread in epidemic form throughout the island nation of Haiti; as of 2014, about
      700,000 cholera cases have been reported, with over 8,000 deaths. While case
      numbers have declined, the more fundamental question of whether the causative
      bacterium, Vibrio cholerae has established an environmental reservoir in the
      surface waters of Haiti remains to be elucidated. In a previous study conducted
      between April 2012 and March 2013, we reported the isolation of toxigenic V.
      cholerae O1 from surface waters in the Ouest Department. After a second year of
      surveillance (April 2013 to March 2014) using identical methodology, we observed
      a more than five-fold increase in the number of water samples containing
      culturable V. cholerae O1 compared to the previous year (1.7% vs 8.6%), with
      double the number of sites having at least one positive sample (58% vs 20%). Both
      seasonal water temperatures and precipitation were significantly related to the
      frequency of isolation. Our data suggest that toxigenic V. cholerae O1 are
      becoming more common in surface waters in Haiti; while the basis for this
      increase is uncertain, our findings raise concerns that environmental reservoirs
      are being established. 

PMID- 25853553
TI  - Identification of novel adipokines in the joint. Differential expression in
      healthy and osteoarthritis tissues.
AB  - OBJECTIVES: Emerging data suggest that several metabolic factors, released mainly
      by white adipose tissue (WAT) and joint tissues, and collectively named
      adipokines, might have a role in the pathophysiology of OA. Recently, novel
      adipokines such as SERPINE2, WISP2, GPNMB and ITIH5 have been identified in WAT.
      The main goal of this study was to analyse the expression of these novel
      adipokines in synovium, infrapatellar fat pad and chondrocytes and to compare the
      expression of these molecules in healthy and OA tissues. METHODS: Synovial
      tissues, infrapatellar fat pad and chondrocytes were obtained from 36 OA patients
      (age 52-85; mean BMI 28.9) who underwent total knee replacement surgery. Healthy
      synovial tissues and infrapatellar fat pad were obtained from 15 traumatic knee
      patients (age 23-53; mean BMI 23.5). mRNA and protein expression were determined
      by qRT-PCR and western blot analysis respectively. RESULTS: All the novel
      adipokines, matter of our study, are expressed in OA synovium, infrapatellar fat
      pad and chondrocytes. Moreover, we detected a differential expression of SERPINE2
      and ITIH5 in OA synovial tissues as compared to healthy samples. Finally, we also
      observed an increased expression of WISP2 in OA infrapatellar fat pad in
      comparison to healthy controls. CONCLUSIONS: In this study we demonstrated for
      the first time the expression of four novel adipokines in different joint tissues
      and how these molecules are differentially expressed in healthy and OA joint
      tissues.

PMID- 25853555
TI  - Density of Trap States and Auger-mediated Electron Trapping in CdTe Quantum-Dot
      Solids.
AB  - Charge trapping is an ubiquitous process in colloidal quantum-dot solids and a
      major limitation to the efficiency of quantum dot based devices such as solar
      cells, LEDs, and thermoelectrics. Although empirical approaches led to a
      reduction of trapping and thereby efficiency enhancements, the exact chemical
      nature of the trapping mechanism remains largely unidentified. In this study, we
      determine the density of trap states in CdTe quantum-dot solids both
      experimentally, using a combination of electrochemical control of the Fermi level
      with ultrafast transient absorption and time-resolved photoluminescence
      spectroscopy, and theoretically, via density functional theory calculations. We
      find a high density of very efficient electron traps centered ~0.42 eV above the
      valence band. Electrochemical filling of these traps increases the electron
      lifetime and the photoluminescence quantum yield by more than an order of
      magnitude. The trapping rate constant for holes is an order of magnitude lower
      that for electrons. These observations can be explained by Auger-mediated
      electron trapping. From density functional theory calculations we infer that the
      traps are formed by dicoordinated Te atoms at the quantum dot surface. The
      combination of our unique experimental determination of the density of trap
      states with the theoretical modeling of the quantum dot surface allows us to
      identify the trapping mechanism and chemical reaction at play during charge
      trapping in these quantum dots. 

PMID- 25853557
TI  - 3D bite modeling and feeding mechanics of the largest living amphibian, the
      Chinese giant salamander Andrias davidianus (Amphibia:Urodela).
AB  - Biting is an integral feature of the feeding mechanism for aquatic and
      terrestrial salamanders to capture, fix or immobilize elusive or struggling prey.
      However, little information is available on how it works and the functional
      implications of this biting system in amphibians although such approaches might
      be essential to understand feeding systems performed by early tetrapods. Herein,
      the skull biomechanics of the Chinese giant salamander, Andrias davidianus is
      investigated using 3D finite element analysis. The results reveal that the prey
      contact position is crucial for the structural performance of the skull, which is
      probably related to the lack of a bony bridge between the posterior end of the
      maxilla and the anterior quadrato-squamosal region. Giant salamanders perform
      asymmetrical strikes. These strikes are unusual and specialized behavior but
      might indeed be beneficial in such sit-and-wait or ambush-predators to capture
      laterally approaching prey. However, once captured by an asymmetrical strike,
      large, elusive and struggling prey have to be brought to the anterior jaw region
      to be subdued by a strong bite. Given their basal position within extant
      salamanders and their "conservative" morphology, cryptobranchids may be useful
      models to reconstruct the feeding ecology and biomechanics of different members
      of early tetrapods and amphibians, with similar osteological and myological
      constraints. 

PMID- 25853556
TI  - Combined biomarker analysis for risk of acute kidney injury in patients with ST
      segment elevation myocardial infarction.
AB  - BACKGROUND: Acute kidney injury (AKI) complicating ST-segment elevation
      myocardial infarction (STEMI) increases subsequent morbidity and mortality. We
      combined the biomarkers of heart failure (HF; B-type natriuretic peptide [BNP]
      and soluble ST2 [sST2]) and renal injury (NGAL [neutrophil gelatinase-associated
      lipocalin] and cystatin C) in predicting the development of AKI in patients with
      STEMI undergoing primary percutaneous coronary intervention (PCI). METHODS AND
      RESULTS: From March 2010 to September 2013, 189 STEMI patients were sequentially
      enrolled and serum samples were collected at presentation for BNP, sST2, NGAL and
      cystatin C analysis. 37 patients (19.6%) developed AKI of varying severity within
      48 hours of presentation. Univariate analysis showed age, Killip class >=2,
      hypertension, white blood cell counts, hemoglobin, estimated glomerular
      filtration rate, blood urea nitrogen, creatinine, and all the four biomarkers
      were predictive of AKI. Serum levels of the biomarkers were correlated with risk
      of AKI and the Acute Kidney Injury Network (AKIN) stage and all significantly
      discriminated AKI (area under the receiver operating characteristic [ROC] curve:
      BNP: 0.86, sST2: 0.74, NGAL: 0.75, cystatin C: 0.73; all P < 0.05). Elevation of
      >=2 of the biomarkers higher than the cutoff values derived from the ROC analysis
      improved AKI risk stratification, regardless of the creatine level (creatinine <
      1.24 mg/dL: odds ratio [OR] 11.25, 95% confidence interval [CI] 1.63-77.92, P =
      0.014; creatinine >= 1.24: OR 15.0, 95% CI 1.23-183.6, P = 0.034). CONCLUSIONS:
      In this study of STEMI patients undergoing primary PCI, the biomarkers of heart
      failure (BNP and sST2) and renal injury (NGAL and cystatin C) at presentation
      were predictive of AKI. High serum levels of the biomarkers were associated with
      an elevated risk and more advanced stage of AKI. Regardless of the creatinine
      level, elevation of >=2 of the biomarkers higher than the cutoff values indicated
      a further rise in AKI risk. Combined biomarker approach may assist in risk
      stratification of AKI in patients with STEMI.

PMID- 25853558
TI  - Bacteria isolated from bats inhibit the growth of Pseudogymnoascus destructans,
      the causative agent of white-nose syndrome.
AB  - Emerging infectious diseases are a key threat to wildlife. Several fungal skin
      pathogens have recently emerged and caused widespread mortality in several
      vertebrate groups, including amphibians, bats, rattlesnakes and humans. White
      nose syndrome, caused by the fungal skin pathogen Pseudogymnoascus destructans,
      threatens several hibernating bat species with extinction and there are few
      effective treatment strategies. The skin microbiome is increasingly understood to
      play a large role in determining disease outcome. We isolated bacteria from the
      skin of four bat species, and co-cultured these isolates with P. destructans to
      identify bacteria that might inhibit or kill P. destructans. We then conducted
      two reciprocal challenge experiments in vitro with six bacterial isolates (all in
      the genus Pseudomonas) to quantify the effect of these bacteria on the growth of
      P. destructans. All six Pseudomonas isolates significantly inhibited growth of P.
      destructans compared to non-inhibitory control bacteria, and two isolates
      performed significantly better than others in suppressing P. destructans growth
      for at least 35 days. In both challenge experiments, the extent of suppression of
      P. destructans growth was dependent on the initial concentration of P.
      destructans and the initial concentration of the bacterial isolate. These results
      show that bacteria found naturally occurring on bats can inhibit the growth of P.
      destructans in vitro and should be studied further as a possible probiotic to
      protect bats from white-nose syndrome. In addition, the presence of these
      bacteria may influence disease outcomes among individuals, populations, and
      species. 

PMID- 25853559
TI  - A coding variant in TMC8 (EVER2) is associated with high risk HPV infection and
      head and neck cancer risk.
AB  - HPV infection is a causal agent in many epithelial cancers, yet our understanding
      of genetic susceptibility to HPV infection and resultant cancer risk is limited.
      Epidermodysplasia Verruciformis is a rare condition of extreme susceptibility to
      cutaneous HPV infection primarily attributable to mutations in TMC6 and TMC8.
      Genetic variation in the TMC6/TMC8 region has been linked to beta-type HPV
      infection and squamous cell carcinoma of the skin, cervical cancer, HPV
      persistence and progression to cervical cancer. Here, we have tested the
      hypothesis that the common TMC8 SNP rs7208422 is associated with high-risk HPV
      infection and risk of head and neck squamous cell carcinoma (HNSCC).
      Seropositivity to the HPV L1 protein (HPV16, 18, 11, 31, 33, 35, 45, 52, 58) was
      measured in 514 cases and 452 population-based controls. Genotype was
      significantly associated with seropositivity to HPV18 L1 (OR TT vs AA = 0.48, 95%
      CI = 0.22-0.99) and borderline significantly associated with HPV16 L1 (OR TT vs
      AA = 0.58, 95% CI = 0.22-1.17). There was a consistent inverse association
      between TMC8 genotype and infection with other HPV types, including statistically
      significant associations for HPV31 and HPV52. Consistent with these results, the
      variant T genotype was associated with a reduced risk of HNSCC (ORAT: 0.63, 95%
      CI 0.45-0.89, ORTT: 0.54, 95% CI 0.36-0.81), even among subjects seronegative for
      all HPV types (ORAT: 0.71, 95% CI 0.45-1.11, ORTT: 0.54, 95% CI 0.31-0.93). Our
      data indicate that common genetic variation in TMC8 is associated with high-risk
      HPV infection and HNSCC etiology. 

PMID- 25853560
TI  - A DIseAse MOdule Detection (DIAMOnD) algorithm derived from a systematic analysis
      of connectivity patterns of disease proteins in the human interactome.
AB  - The observation that disease associated proteins often interact with each other
      has fueled the development of network-based approaches to elucidate the molecular
      mechanisms of human disease. Such approaches build on the assumption that protein
      interaction networks can be viewed as maps in which diseases can be identified
      with localized perturbation within a certain neighborhood. The identification of
      these neighborhoods, or disease modules, is therefore a prerequisite of a
      detailed investigation of a particular pathophenotype. While numerous heuristic
      methods exist that successfully pinpoint disease associated modules, the basic
      underlying connectivity patterns remain largely unexplored. In this work we aim
      to fill this gap by analyzing the network properties of a comprehensive corpus of
      70 complex diseases. We find that disease associated proteins do not reside
      within locally dense communities and instead identify connectivity significance
      as the most predictive quantity. This quantity inspires the design of a novel
      Disease Module Detection (DIAMOnD) algorithm to identify the full disease module
      around a set of known disease proteins. We study the performance of the algorithm
      using well-controlled synthetic data and systematically validate the identified
      neighborhoods for a large corpus of diseases. 

PMID- 25853561
TI  - A 9-year retrospective evaluation of 102 pressure ulcer reconstructions.
AB  - OBJECTIVE: Several pressure ulcer (PU) risk factors including paralysis and age
      greater than 70 have been identified, while others such as nutrition are debated.
      The object of this study is to identify perioperative risk factors that may
      predict improved outcomes and reduced complications in primary and recurrent PU
      reconstructions. METHOD: A retrospective chart review of patients treated
      surgically for PUs from 2004 to 2013 at the University of Toledo Medical Center,
      Toledo, Ohio, US, was completed. Data collected included ulcer and medical
      history, as well as risk factors, complications and postoperative outcome. Data
      were statistically analysed for perioperative variances between primary and
      recurrent ulcers and closure status. RESULTS: A total of 49 patients with 102
      reconstructions were reviewed. Spinal cord injured patients accounted for 90%
      receiving flap coverage of ulcers. Numerous differences between primary and
      recurrent ulcers were identified, including ulcer location, patient nutritional
      status, wound infection, postoperative course and recurrence. Multivariate
      analysis revealed a flap reconstruction prediction model using creatinine,
      haematocrit, haemoglobin, and prealbumin that is able to successfully predict
      closure outcome in 83.6% of cases. CONCLUSION: Many factors play a role in the
      development, course and treatment of PUs. It is vital to understand the role of
      patient risk factors in the development of PUs, to direct subsequent management
      and reconstruction, and to prevent future recurrences. DECLARATION OF INTEREST:
      The authors have no conflicts of interest to disclose.

PMID- 25853563
TI  - Clinical evaluation of a silver-impregnated foam dressing in paediatric partial
      thickness burns.
AB  - OBJECTIVE: Mepilex Ag, a silver-impregnated foam dressing, was introduced to our
      institution in 2007 and our outcomes in the treatment of paediatric burns were
      observed to improve significantly. In order to confirm these observations, we
      wanted to evaluate the results of using the silver-impregnated foam dressing in
      partial-thickness paediatric burns. METHOD: In this retrospective study, the St.
      Christopher's Hospital burn registry was used to identify subjects, who were
      otherwise in excellent health at baseline, over an18-month period. Outcomes
      included length of stay, intravenous narcotic use, and time to healing. No direct
      comparative studies were performed. This was followed by a non-comparative
      prospective study involving 22 paediatric patients, aged 1-4 years, with partial
      thickness burns. This was a sub-study of a larger randomised controlled trial
      involving adults with partial-thickness burns, comparing the silver-impregnated
      foam dressing with Silvadene. RESULTS: In the retrospective part of the study,
      the silver-impregnated foam dressing was used successfully for the treatment of
      partial-thickness paediatric burns, with few complications and infections,
      allowing a shorter hospital stay, fewer dressings, and less pain medication than
      for historical controls. In the non-comparative prospective study, of 22
      paediatric patients 50% healed completely within 1 week of treatment. The mean
      length of stay was 3.77 days and the mean number of dressings used was 1.64.
      Although narcotic usage was not assessed, patient surveys showed stinging or
      burning to be recorded as 'never' in 13 patients, 'rarely' in 8 patients, and
      'sometimes' in 1 patient. CONCLUSION: The silver-impregnated foam dressing is
      effective and safe for use in partial-thickness paediatric burns, eliminating the
      need for daily dressings. DECLARATION OF INTEREST: The study was supported by an
      educational grant from Molnlycke Health Care.

PMID- 25853564
TI  - Functional characterization of the spf/ash splicing variation in OTC deficiency
      of mice and man.
AB  - The spf/ash mouse model of ornithine transcarbamylase (OTC) deficiency, a severe
      urea cycle disorder, is caused by a mutation (c.386G>A; p.R129H) in the last
      nucleotide of exon 4 of the Otc gene, affecting the 5' splice site and resulting
      in partial use of a cryptic splice site 48 bp into the adjacent intron. The
      equivalent nucleotide change and predicted amino acid change is found in OTC
      deficient patients. Here we have used liver tissue and minigene assays to dissect
      the transcriptional profile resulting from the "spf/ash" mutation in mice and
      man. For the mutant mouse, we confirmed liver transcripts corresponding to
      partial intron 4 retention by the use of the c.386+48 cryptic site and to
      normally spliced transcripts, with exon 4 always containing the c.386G>A
      (p.R129H) variant. In contrast, the OTC patient exhibited exon 4 skipping or
      c.386G>A (p.R129H)-variant exon 4 retention by using the natural or a cryptic
      splice site at nucleotide position c.386+4. The corresponding OTC tissue enzyme
      activities were between 3-6% of normal control in mouse and human liver. The use
      of the cryptic splice sites was reproduced in minigenes carrying murine or human
      mutant sequences. Some normally spliced transcripts could be detected in
      minigenes in both cases. Antisense oligonucleotides designed to block the murine
      cryptic +48 site were used in minigenes in an attempt to redirect splicing to the
      natural site. The results highlight the relevance of in depth investigations of
      the molecular mechanisms of splicing mutations and potential therapeutic
      approaches. Notably, they emphasize the fact that findings in animal models may
      not be applicable for human patients due to the different genomic context of the
      mutations. 

PMID- 25853565
TI  - Regiospecific Hetero-Assembly of DNA-Functionalized Plasmonic Upconversion
      Superstructures.
AB  - We report a novel strategy for regiospecific hetero-assembly of DNA-modified gold
      nanoparticles (DNA-AuNPs) onto upconversion nanoparticles (UCNPs) into hybrid lab
      on-a-particle systems. The DNA-AuNPs have been assembled onto the hexagonal plate
      like UCNPs with well-regulated stoichiometry and controlled organization onto the
      different facets of UCNP, forming various addressable superstructures. The fine
      tuning of stoichiometry and organization is realized by biorecognition
      specificity of DNA toward specific crystal facets of UCNPs. Such a hetero
      assembled DNA-AuNP/UCNP system maintains both plasmonic resonance of AuNPs and
      fluorescent properties of UCNPs, allowing targeted dual-modality imaging of
      cancer cells using an aptamer. 

PMID- 25853567
TI  - Rhodopseudomonas palustris CGA010 Proteome Implicates Extracytoplasmic Function
      Sigma Factor in Stress Response.
AB  - Rhodopseudomonas palustris encodes 16 extracytoplasmic function (ECF) sigma
      factors. To begin to investigate the regulatory network of one of these ECF sigma
      factors, the whole proteome of R. palustris CGA010 was quantitatively analyzed by
      tandem mass spectrometry from cultures episomally expressing the ECF
      sigma(RPA4225) (ecfT) versus a WT control. Among the proteins with the greatest
      increase in abundance were catalase KatE, trehalose synthase, a DPS-like protein,
      and several regulatory proteins. Alignment of the cognate promoter regions
      driving expression of several upregulated proteins suggested a conserved binding
      motif in the -35 and -10 regions with the consensus sequence GGAAC-18N-TT.
      Additionally, the putative anti-sigma factor RPA4224, whose gene is contained in
      the same predicted operon as RPA4225, was identified as interacting directly with
      the predicted response regulator RPA4223 by mass spectrometry of affinity
      isolated protein complexes. Furthermore, another gene (RPA4226) coding for a
      protein that contains a cytoplasmic histidine kinase domain is located
      immediately upstream of RPA4225. The genomic organization of orthologs for these
      four genes is conserved in several other strains of R. palustris as well as in
      closely related alpha-Proteobacteria. Taken together, these data suggest that ECF
      sigma(RPA4225) and the three additional genes make up a sigma factor mimicry
      system in R. palustris. 

PMID- 25853566
TI  - Salinity regulation of the interaction of halovirus SNJ1 with its host and
      alteration of the halovirus replication strategy to adapt to the variable
      ecosystem.
AB  - Halovirus is a major force that affects the evolution of extreme halophiles and
      the biogeochemistry of hypersaline environments. However, until now, the
      systematic studies on the halovirus ecology and the effects of salt concentration
      on virus-host systems are lacking. To provide more valuable information for
      understanding ecological strategies of a virus-host system in the hypersaline
      ecosystem, we studied the interaction between halovirus SNJ1 and its host
      Natrinema sp.J7-2 under various NaCl concentrations. We found that the adsorption
      rate and lytic rate increased with salt concentration, demonstrating that a
      higher salt concentration promoted viral adsorption and proliferation. Contrary
      to the lytic rate, the lysogenic rate decreased as the salt concentration
      increased. Our results also demonstrated that cells incubated at a high salt
      concentration prior to infection increased the ability of the virus to adsorb and
      lyse its host cells; therefore, the physiological status of host cells also
      affected the virus-host interaction. In conclusion, SNJ1 acted as a predator,
      lysing host cells and releasing progeny viruses in hypersaline environments; in
      low salt environments, viruses lysogenized host cells to escape the damage from
      low salinity. 

PMID- 25853569
TI  - An in vitro study comparing two dose regimes of fresh frozen plasma on
      conventional and thromboelastographic tests of coagulation after major hepatic
      resection.
AB  - BACKGROUND: After hepatic resection, post-operative increases in international
      normalised ratio (INR) are frequent, but rarely associated with bleeding
      complication. Coagulation as assessed by thrombin generation may be normal,
      despite the increased INR. This study tests the hypothesis that viscoelastic
      tests (VET) of coagulation remain normal, despite mild elevations in INR,
      examines the efficacy of fresh frozen plasma (FFP) in reversing prolongation of
      INR in such patients and determines the effect of FFP on VET. METHODS: A
      prospective cohort study of 47 patients undergoing major hepatectomy. In vitro
      spiking with FFP (7.5 and 15 mL kg(-1)) was carried out if post-operative day 2
      (POD2) INR levels were >=1.5. Thromboelastography (TEG(r)) and INR were measured
      before and after FFP spiking. RESULTS: Blood from patients with an INR  >= 1.5 on
      POD2 was spiked with FFP. There was a significant reduction in the INR from 1.94
      [standard deviation (SD): 0.59] to 1.46 (SD: 0.27, P = 0.005) and 1.36 (SD: 0.18,
      P = 0.0007) with FFP 7.5 or 15 mL kg(-1), respectively. At baseline, the TEG R
      time [6.17 min (NR, 9-27 min)] and maximum amplitude (MA) [66.9 mm (NR, 44-64
      mm)] were hypercoagulable, and remained so on POD2 for the R-time (6.7 min), but
      fell to within the normal range for the MA (54.0 mm). FFP spiking had no
      significant effect on TEG variables. CONCLUSIONS: Despite the rise in INR after
      hepatectomy, VET do not show evidence of hypocoagulability. In vitro addition of
      FFP had no significant effect on TEG parameters. Clinical use of FFP in this
      situation is questionable.

PMID- 25853570
TI  - Response of moose hunters to predation following wolf return in Sweden.
AB  - BACKGROUND: Predation and hunter harvest constitute the main mortality factors
      affecting the size and dynamics of many exploited populations. The re
      colonization by wolves (Canis lupus) of the Scandinavian Peninsula may therefore
      substantially reduce hunter harvest of moose (Alces alces), the main prey of
      wolves. METHODOLOGY/PRINCIPAL FINDINGS: We examined possible effects of wolf
      presence on hunter harvest in areas where we had data before and after wolf
      establishment (n = 25), and in additional areas that had been continuously
      exposed to wolf predation during at least ten years (n = 43). There was a general
      reduction in the total number of moose harvested (n = 31,827) during the ten year
      study period in all areas irrespective of presence of wolves or not. However, the
      reduction in hunter harvest was stronger within wolf territories compared to
      control areas without wolves. The reduction in harvest was larger in small (500
      800 km2) compared to large (1,200-1,800 km2) wolf territories. In areas with
      newly established wolf territories moose management appeared to be adaptive with
      regard to both managers (hunting quotas) and to hunters (actual harvest). In
      these areas an instant reduction in moose harvest over-compensated the estimated
      number of moose killed annually by wolves and the composition of the hunted
      animals changed towards a lower proportion of adult females.
      CONCLUSIONS/SIGNIFICANCE: We show that the re-colonization of wolves may result
      in an almost instant functional response by another large predator-humans-that
      reduced the potential for a direct numerical effect on the density of wolves'
      main prey, the moose. Because most of the worlds' habitat that will be available
      for future colonization by large predators are likely to be strongly influenced
      by humans, human behavioural responses may constitute a key trait that govern the
      impact of large predators on their prey.

PMID- 25853568
TI  - FRESCo: finding regions of excess synonymous constraint in diverse viruses.
AB  - BACKGROUND: The increasing availability of sequence data for many viruses
      provides power to detect regions under unusual evolutionary constraint at a high
      resolution. One approach leverages the synonymous substitution rate as a
      signature to pinpoint genic regions encoding overlapping or embedded functional
      elements. Protein-coding regions in viral genomes often contain overlapping RNA
      structural elements, reading frames, regulatory elements, microRNAs, and
      packaging signals. Synonymous substitutions in these regions would be selectively
      disfavored and thus these regions are characterized by excess synonymous
      constraint. Codon choice can also modulate transcriptional efficiency,
      translational accuracy, and protein folding. RESULTS: We developed a phylogenetic
      codon model-based framework, FRESCo, designed to find regions of excess
      synonymous constraint in short, deep alignments, such as individual viral genes
      across many sequenced isolates. We demonstrated the high specificity of our
      approach on simulated data and applied our framework to the protein-coding
      regions of approximately 30 distinct species of viruses with diverse genome
      architectures. CONCLUSIONS: FRESCo recovers known multifunctional regions in well
      characterized viruses such as hepatitis B virus, poliovirus, and West Nile virus,
      often at a single-codon resolution, and predicts many novel functional elements
      overlapping viral genes, including in Lassa and Ebola viruses. In a number of
      viruses, the synonymously constrained regions that we identified also display
      conserved, stable predicted RNA structures, including putative novel elements in
      multiple viral species.

PMID- 25853571
TI  - Socioeconomic inequalities in mortality and repeated measurement of explanatory
      risk factors in a 25 years follow-up.
AB  - BACKGROUND: Socioeconomic inequalities in mortality can be explained by different
      groups of risk factors. However, little is known whether repeated measurement of
      risk factors can provide better explanation of socioeconomic inequalities in
      health. Our study examines the extent to which relative educational and income
      inequalities in mortality might be explained by explanatory risk factors
      (behavioral, psychosocial, biomedical risk factors and employment) measured at
      two points in time, as compared to one measurement at baseline. METHODS AND
      FINDINGS: From the Norwegian total county population-based HUNT Study (years 1984
      86 and 1995-1997, respectively) 61 513 men and women aged 25-80 (82.5% of all
      enrolled) were followed-up for mortality in 25 years until 2009, employing a
      discrete time survival analysis. Socioeconomic inequalities in mortality were
      observed. As compared to their highest socioeconomic counterparts, the lowest
      educated men had an OR (odds ratio) of 1.41 (95% CI 1.29-1.55) and for the lowest
      income quartile OR = 1.59 (1.48-1.571), for women OR = 1.35 (1.17-1.55), and OR =
      1.40 (1.28-1.52), respectively. Baseline explanatory variables attenuated the
      association between education and income with mortality by 54% and 54% in men,
      respectively, and by 69% and 18% in women. After entering time-varying variables,
      this attainment increased to 63% and 59% in men, respectively, and to 25%
      (income) in women, with no improvement in regard to education in women. Change in
      biomedical factors and employment did not amend the explanation. CONCLUSIONS:
      Addition of a second measurement for risk factors provided only a modest
      improvement in explaining educational and income inequalities in mortality in
      Norwegian men and women. Accounting for change in behavior provided the largest
      improvement in explained inequalities in mortality for both men and women, as
      compared to measurement at baseline. Psychosocial factors explained the largest
      share of income inequalities in mortality for men, but repeated measurement of
      these factors contributed only to modest improvement in explanation. Further
      comparative research on the relative importance of explanatory pathways assessed
      over time is needed.

PMID- 25853572
TI  - Effects of maternal diet and exercise during pregnancy on glucose metabolism in
      skeletal muscle and fat of weanling rats.
AB  - Obesity during pregnancy contributes to the development of metabolic disorders in
      offspring. Maternal exercise may limit gestational weight gain and ameliorate
      these programming effects. We previously showed benefits of post-weaning
      voluntary exercise in offspring from obese dams. Here we examined whether
      voluntary exercise during pregnancy influences lipid and glucose homeostasis in
      muscle and fat in offspring of both lean and obese dams. Female Sprague-Dawley
      rats were fed chow (C) or high fat (F) diet for 6 weeks before mating. Half
      underwent voluntary exercise (CE/FE) with a running wheel introduced 10 days
      prior to mating and available until the dams delivered; others remained sedentary
      (CS/FS). Male and female pups were killed at postnatal day (PND)19 and
      retroperitoneal fat and gastrocnemius muscle were collected for gene expression.
      Lean and obese dams achieved similar modest levels of exercise. At PND1, both
      male and female pups from exercised lean dams were significantly lighter (CE
      versus CS), with no effect in those from obese dams. At PND19, maternal obesity
      significantly increased offspring body weight and adiposity, with no effect of
      maternal exercise. Exercise significantly reduced insulin concentrations in males
      (CE/FE versus CS/FS), with reduced glucose in male FE pups. In males, maternal
      obesity significantly decreased muscle myogenic differentiation 1 (MYOD1) and
      glucose transporter type 4 (GLUT4) mRNA expressions (FS vs CS); these were
      normalized by exercise. Maternal exercise upregulated adipose GLUT4, interleukin
      6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and peroxisome proliferator
      activated receptor gamma coactivator 1 alpha (PGC1alpha) mRNA expression in
      offspring of dams consuming chow. Modest voluntary exercise during pregnancy was
      associated with lower birth weight in pups from lean dams. Maternal exercise
      appeared to decrease the metabolic risk induced by maternal obesity, improving
      insulin/glucose metabolism, with greater effects in male than female offspring. 

PMID- 25853573
TI  - Postoperative metamorphopsia in macula-off rhegmatogenous retinal detachment:
      associations with visual function, vision related quality of life, and optical
      coherence tomography findings.
AB  - PURPOSE: To evaluate postoperative metamorphopsia in macula-off rhegmatogenous
      retinal detachment (RRD) and its association with visual function, vision related
      quality of life, and optical coherence tomography (OCT) findings. METHODS: 45
      patients with primary macula-off RRD were included. At 12 months postoperatively,
      data on metamorphopsia using sine amsler charts (SAC), best corrected visual
      acuity (BCVA), letter contrast sensitivity, color vision (saturated and
      desaturated color confusion indexes), critical print size, reading acuity, the 25
      item National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25), and
      OCT, were obtained. RESULTS: Metamorphopsia was present in 39 patients (88.6%),
      with most of them (n = 35, 77.8%) showing only mild metamorphopsia (SAC score =
      1). Patients with metamorphopsia had significantly worse postoperative BCVA (p =
      0.02), critical print size (p<0.0005), and reading acuity (p = 0.001) compared to
      patients without metamorphopsia. Other visual function outcomes and NEI-VFQ-25
      overall composite score were all also somewhat lower in patients with
      metamorphopsia, but this did not reach statistical significance. No association
      with OCT findings was present. CONCLUSION: The prevalence of postoperative
      metamorphopsia in macula-off RRD patients is high, however, the degree of
      metamorphopsia is relatively low. When metamorphopsia is present, visual
      functions seem to be compromised, while vision related quality of life is only
      mildly affected.

PMID- 25853574
TI  - Timely Surgical Follow-up for Melanoma Among Medicare Beneficiaries.

PMID- 25853575
TI  - Calibration of the gamma-H2AX DNA double strand break focus assay for internal
      radiation exposure of blood lymphocytes.
AB  - DNA double strand break (DSB) formation induced by ionizing radiation exposure is
      indicated by the DSB biomarkers gamma-H2AX and 53BP1. Knowledge about DSB foci
      formation in-vitro after internal irradiation of whole blood samples with
      radionuclides in solution will help us to gain detailed insights about dose
      response relationships in patients after molecular radiotherapy (MRT). Therefore,
      we studied the induction of radiation-induced co-localizing gamma-H2AX and 53BP1
      foci as surrogate markers for DSBs in-vitro, and correlated the obtained foci per
      cell values with the in-vitro absorbed doses to the blood for the two most
      frequently used radionuclides in MRT (I-131 and Lu-177). This approach led to an
      in-vitro calibration curve. Overall, 55 blood samples of three healthy volunteers
      were analyzed. For each experiment several vials containing a mixture of whole
      blood and radioactive solutions with different concentrations of isotonic NaCl
      diluted radionuclides with known activities were prepared. Leukocytes were
      recovered by density centrifugation after incubation and constant blending for 1
      h at 37 degrees C. After ethanol fixation they were subjected to two-color
      immunofluorescence staining and the average frequencies of the co-localizing
      gamma-H2AX and 53BP1 foci/nucleus were determined using a fluorescence microscope
      equipped with a red/green double band pass filter. The exact activity was
      determined in parallel in each blood sample by calibrated germanium detector
      measurements. The absorbed dose rates to the blood per nuclear disintegrations
      occurring in 1 ml of blood were calculated for both isotopes by a Monte Carlo
      simulation. The measured blood doses in our samples ranged from 6 to 95 mGy. A
      linear relationship was found between the number of DSB-marking foci/nucleus and
      the absorbed dose to the blood for both radionuclides studied. There were only
      minor nuclide-specific intra- and inter-subject deviations. 

PMID- 25853577
TI  - Edoxaban (Savaysa)--the fourth new oral anticoagulant.

PMID- 25853578
TI  - Secukinumab (Cosentyx) for psoriasis.

PMID- 25853576
TI  - Haplotype phasing and inheritance of copy number variants in nuclear families.
AB  - DNA copy number variants (CNVs) that alter the copy number of a particular DNA
      segment in the genome play an important role in human phenotypic variability and
      disease susceptibility. A number of CNVs overlapping with genes have been shown
      to confer risk to a variety of human diseases thus highlighting the relevance of
      addressing the variability of CNVs at a higher resolution. So far, it has not
      been possible to deterministically infer the allelic composition of different
      haplotypes present within the CNV regions. We have developed a novel
      computational method, called PiCNV, which enables to resolve the haplotype
      sequence composition within CNV regions in nuclear families based on SNP
      genotyping microarray data. The algorithm allows to i) phase normal and CNV
      carrying haplotypes in the copy number variable regions, ii) resolve the allelic
      copies of rearranged DNA sequence within the haplotypes and iii) infer the
      heritability of identified haplotypes in trios or larger nuclear families. To our
      knowledge this is the first program available that can deterministically phase
      null, mono-, di-, tri- and tetraploid genotypes in CNV loci. We applied our
      method to study the composition and inheritance of haplotypes in CNV regions of
      30 HapMap Yoruban trios and 34 Estonian families. For 93.6% of the CNV loci,
      PiCNV enabled to unambiguously phase normal and CNV-carrying haplotypes and
      follow their transmission in the corresponding families. Furthermore, allelic
      composition analysis identified the co-occurrence of alternative allelic copies
      within 66.7% of haplotypes carrying copy number gains. We also observed less
      frequent transmission of CNV-carrying haplotypes from parents to children
      compared to normal haplotypes and identified an emergence of several de novo
      deletions and duplications in the offspring. 

PMID- 25853579
TI  - Gardasil 9--a broader HPV vaccine.

PMID- 25853580
TI  - OTC fluticason nasal spray for allergic rhinitis.

PMID- 25853581
TI  - Spiriva Respimat--an oral inhalation spray for COPD.

PMID- 25853582
TI  - Macrophage inhibitory cytokine 1 biomarker serum immunoassay in combination with
      PSA is a more specific diagnostic tool for detection of prostate cancer.
AB  - BACKGROUND: Prostate cancer (PCa) is the most common malignancy among men in the
      United States. Though highly sensitive, the often-used prostate-specific antigen
      (PSA) test has low specificity which leads to overdiagnosis and overtreatment of
      PCa. This paper presents results of a retrospective study that indicates that
      testing for macrophage inhibitory cytokine 1 (MIC-1) concentration along with the
      PSA assay could provide much improved specificity to the assay. METHODS: The MIC
      1 serum level was determined by a novel p-Chip-based immunoassay run on 70
      retrospective samples. The assay was configured on p-Chips, small integrated
      circuits (IC) capable of storing in their electronic memories a serial number to
      identify the molecular probe immobilized on its surface. The distribution of MIC
      1 and pre-determined PSA concentrations were displayed in a 2D plot and the
      predictive power of the dual MIC-1/PSA assay was analyzed. RESULTS: MIC-1
      concentration in serum was elevated in PCa patients (1.44 ng/ml) compared to
      normal and biopsy-negative individuals (0.93 ng/ml and 0.88 ng/ml, respectively).
      In addition, the MIC-1 level was correlated with the progression of PCa. The area
      under the receiver operator curve (AUC-ROC) was 0.81 providing an assay
      sensitivity of 83.3% and specificity of 60.7% by using a cutoff of 0.494 for the
      logistic regression value of MIC-1 and PSA. Another approach, by defining high
      frequency PCa zones in a two-dimensional plot, resulted in assay sensitivity of
      78.6% and specificity of 89.3%. CONCLUSIONS: The analysis based on correlation of
      MIC-1 and PSA concentrations in serum with the patient PCa status improved the
      specificity of PCa diagnosis without compromising the high sensitivity of the PSA
      test alone and has potential for PCa prognosis for patient therapy strategies.

PMID- 25853584
TI  - Measures of respiratory function correlate with fatigue in ambulatory persons
      with multiple sclerosis.
AB  - PURPOSE: This article examines the association between measures of respiratory
      muscle function and fatigue in individuals with mild-to-moderate disability
      multiple sclerosis (MS). METHODS: This was a cross-sectional study of 37
      ambulatory volunteers with MS (28 F/9 M, 52.7 +/- 10.2 years, Expanded Disability
      Status Scale [EDSS] = 3.5 +/- 1.9). No patients withdrew from the study. Primary
      outcome variables included measures of respiratory function: maximal inspiratory
      (MIP) and expiratory pressures (MEP), forced vital capacity (FVC), forced
      expiratory volume in 1 s (FEV1), maximal voluntary ventilation (MVV12); and a
      self-reported measure of fatigue: the Modified Fatigue Impact Scale (MFIS).
      Secondary measures included 6-min walking test (6MWT), a timed stair climb, the
      Short Form (SF)-36, the Epworth Sleepiness Scale and the Physical Activity and
      Disability Scale (PADS). RESULTS: Significant correlations were shown between
      expiratory muscle strength (MEP) and the MFIS total (p < 0.03, r = -0.362) and
      between MEP and physical fatigue scores (p < 0.03, r = -0.360), as well as
      between MVV12 percent predicted (respiratory muscle endurance) and both the 6MWT
      (p = 0.045, r = 0.346) and the Epworth Sleepiness Scale (p = 0.006, r = 0.447).
      CONCLUSIONS: Respiratory muscle performance is correlated with perceived fatigue
      (MFIS), whereas respiratory endurance correlated to reductions in physical
      function and sleep quality among individuals with mild-to-moderate severity MS.
      Implications for Rehabilitation Multiple sclerosis (MS) results in peripheral and
      respiratory muscle weakness and affected individuals report fatigue as one of
      their most disabling symptoms. Expiratory muscle strength was correlated with
      self-reported physical fatigue, while respiratory muscle endurance was correlated
      with functional performance and sleepiness. Respiratory muscle strength was not
      correlated with lung spirometry testing. These findings highlight the importance
      of considering the effects of respiratory muscle weakness when evaluating causes
      of fatigue among individuals with mild-to-moderate MS.

PMID- 25853583
TI  - Chemical characterization of gallstones: an approach to explore the
      aetiopathogenesis of gallstone disease in Sri Lanka.
AB  - INTRODUCTION: Records on gallstones and associated ailments in Sri Lankan
      community are scarce, despite frequent detection of gallstone disease.
      Identification of the chemical composition of gallstones in the local setting is
      important in defining aetiopathogenic factors which in turn are useful in
      implementing therapeutic and preventive strategies. This study aimed to describe
      the chemical composition of gallstones and the socio-demographic factors of a
      cohort of Sri Lankan patients with gallstone disease. MATERIALS AND METHODS: Data
      on clinical and socio-demographic factors, and gallstones removed at surgery were
      collected from patients with cholelithiasis admitted to Teaching Hospital,
      Peradeniya, Sri Lanka from May 2011 to December 2012. External and cross
      sectional morphological features of gallstones were recorded by naked eye
      observation. Compositional analysis was carried out by Fourier Transform Infrared
      Spectroscopy, X - ray Powder Diffraction, and Atomic Absorption
      Spectrophotometry. Scanning Electron Microscopy was used to identify the
      microstructure of gallstones. RESULTS: Data of 102 patients were analyzed. Of
      them majority (n = 77, 76%) were females with a female: male ratio of 3:1. Mean
      age of the study group was 46.1+/-11.6 years. All the patients had primary
      gallbladder stones. According to the physical and chemical analysis, majority (n
      = 54, 53%) were pigment gallstones followed by mixed cholesterol gallstones (n =
      38, 37%). Only 10 (9%) had pure cholesterol gallstones. Calcium bilirubinate,
      calcium carbonate and calcium phosphate were the commonest calcium salts
      identified in pigment gallstones and core of mixed cholesterol gallstones.
      CONCLUSION: Presence of a pigment nidus in gallstones is a common feature in
      majority of Sri Lankan patients denoting the possible role of elevated
      unconjugated bilirubin in bile on the pathogenesis of GS. Hence it is imperative
      to explore this further to understand the aetiopathogenesis of GS among Sri
      Lankans.

PMID- 25853585
TI  - Surface microstructure of dental implants before and after insertion: an in vitro
      study by means of scanning probe microscopy.
AB  - INTRODUCTION: The surface microstructure of dental implants affects
      osseointegration, which makes their accurate topographic characterization
      important. We defined a procedure for evaluation of implant topography before
      (pre-) and after (post-) in vitro implantation test in bovine bone. MATERIALS AND
      METHODS: The apical morphology of ten implants was analyzed in pre- and post
      conditions using atomic force microscopy or 3D profilometry. We extracted four
      topographical parameters (two amplitude, 1 spatial, and 1 hybrid) and assessed
      the differences by analysis of variance. RESULTS AND DISCUSSION: The implant with
      coating (Spline Twist MP-1 HA) was damaged. The two implants with highest pre
      amplitude parameters (Pitt Easy VTPS, TLR3815) maintained their character on
      testing. Pitt Easy PURETEX and OT-F1 were the only nondamaged implants whose
      amplitude parameters increased. The surface area underwent minor changes even
      when the texture changed (Tri-Vent, Pitt Easy PURETEX, Exp #1). The implants that
      ranked the lowest in all parameters before implantation were DT4013TI, Tri-Vent,
      OT-F1, and Exp #2. On testing, DT4013TI showed the highest decrease in values,
      whereas Tri-Vent showed the highest increase in surface area. All the
      experimental implants showed similar topographic properties both pre- and post
      test. CONCLUSION: For most implants, no major changes occurred in surface
      topography on implantation. The procedure applied seems promising to evaluate the
      degradation of implant surface on insertion.

PMID- 25853586
TI  - Distinguishing effects of ultraviolet exposure and chlorination on the horizontal
      transfer of antibiotic resistance genes in municipal wastewater.
AB  - Growing attention has been paid to the dissemination of antibiotic resistance
      genes (ARGs) in wastewater microbial communities; however, the disinfection
      processes, as microbial control technologies, have not been evaluated for their
      impacts on ARGs transfer. In this study, the effects of ultraviolet (UV)
      disinfection and chlorination on the frequency of ARGs transfer have been
      explored based on the conjugative transfer model between Gram-negative strains of
      E. coli. The results indicated that UV disinfection and chlorination exhibit
      distinct influences on the conjugative transfer. Low UV doses (up to 8 mJ/cm2)
      had little influence on the frequency of conjugative transfer, and UV exposure
      only decreased the bacterial number but did not change the cell permeability. By
      comparison, low chlorine doses (up to 40 mg Cl min/L) significantly promoted the
      frequency of conjugative transfer by 2-5-fold. The generated chloramine
      stimulated the bacteria and improved the cell permeability. More pilus were
      induced on the surface of conjugative cells, which acted as pathways for ARGs
      transfer. The frequency of ARG transfers was greatly suppressed by high doses of
      UV (>10 mJ/cm2) or chlorine (>80 mg Cl min/L).

PMID- 25853587
TI  - Sesquiterpene Lactone Composition of Wild and Cultivated Sunflowers and
      Biological Activity against an Insect Pest.
AB  - Sesquiterpene lactones in sunflowers, Helianthus spp., are important to
      interactions with pathogens, weeds, and insects. Across a broad range of
      Helianthus annuus, differences in composition of sesquiterpene lactones extracted
      from disc florets were found between wild and cultivated sunflowers and also
      between distinct groups of inbreds used to produce sunflower hybrids.
      Discriminant function analysis showed the presence and relative abundance of
      argophyllone B, niveusin B, and 15-hydroxy-3-dehydrodesoxyfruticin were usually
      (75%) effective at classifying wild sunflowers, cultivated inbreds, and hybrids.
      Argophyllone B reduced the larval mass of the sunflower moth, Homeosoma
      electellum, by >30%, but only at a dose greater than that found in florets. Low
      doses of mixed extracts from cultivated florets produced a similar (~40%)
      reduction in larval mass, suggesting combinations of sesquiterpene lactones act
      additively. Although the results support a role for sesquiterpene lactones in
      herbivore defense of cultivated sunflowers, additional information is needed to
      use these compounds purposefully in breeding. 

PMID- 25853588
TI  - Rutile phase n- and p-type anodic titania nanotube arrays with square-shaped pore
      morphologies.
AB  - Rutile-phase TiO2 nanotube arrays without broken walls were formed by annealing
      of anodically formed nanotubes in a propane flame at 650  degrees C and in air at
      750  degrees C. An unusual morphological transformation was observed from the
      ellipsoidal pore-shapes of titania nanotubes grown in aqueous electrolyte to a
      square-shaped pore structure subsequent to the anneals. 750  degrees C annealed
      nanotubes were found to be lightly p-type, rare in TiO2. 

PMID- 25853589
TI  - Surfactant-induced assembly of enzymatically-stable peptide hydrogels.
AB  - The secondary structure of peptides in the presence of interacting additives is
      an important topic of study, having implications in the application of peptide
      science to a broad range of modern technologies. Surfactants constitute a class
      of biologically relevant compounds that are known to influence both peptide
      conformation and aggregation or assembly. We have characterized the secondary
      structure of a linear nonapeptide composed of a hydrophobic alanine/phenylalanine
      core flanked by hydrophilic acid/amine units. We show that the anionic surfactant
      sodium dodecyl sulfate (SDS) induces the formation of beta-sheets and macroscopic
      gelation in this otherwise unstructured peptide. Through comparison to related
      additives, we propose that SDS-induced secondary structure formation is the
      result of amphiphilicity created by electrostatic binding of SDS to the peptide.
      In addition, we demonstrate a novel utility of surfactants in manipulating and
      stabilizing peptide nanostructures. SDS is used to simultaneously induce
      secondary structure in a peptide and to inhibit the activity of a model enzyme,
      resulting in a peptide hydrogel that is impervious to enzymatic degradation.
      These results complement our understanding of the behavior of peptides in the
      presence of interacting secondary molecules and provide new potential pathways
      for programmable organization of peptides by the addition of such components. 

PMID- 25853590
TI  - Characteristics and Outcomes of HIV-Infected Patients With Severe Sepsis:
      Continued Risk in the Post-Highly Active Antiretroviral Therapy Era.
AB  - OBJECTIVES: Although highly active antiretroviral therapy has led to improved
      survival in HIV-infected individuals, outcomes for HIV-infected patients with
      sepsis in the post-highly active antiretroviral therapy era are conflicting.
      Access to highly active antiretroviral therapy and healthcare disparities
      continue to affect outcomes. We hypothesized that HIV-infected patients with
      severe sepsis would have worse outcomes compared with their HIV-uninfected
      counterparts in a large safety-net hospital where access to healthcare is low and
      delivery of critical care is delayed. DESIGN: Secondary analysis of an ongoing
      prospective observational study between 2006 and 2010. SETTING: Three adult ICUs
      (medical ICU, surgical ICU, and neurologic ICU) at Grady Memorial Hospital,
      Atlanta, GA. PATIENTS: Adult patients with severe sepsis in the ICU.
      INTERVENTIONS: Baseline patient characteristics and clinical outcomes were
      collected. HIV-infected and HIV-uninfected patients with sepsis were compared
      using t tests, chi-square tests, and logistic regression; p values less than 0.05
      indicated significance. MEASUREMENTS AND MAIN RESULTS: Of 1,095 patients with
      severe sepsis enrolled, 165 (15%) were positive for HIV, with a median CD4 count
      of 41 (8-167). Twenty-two percent of HIV-infected patients were on highly active
      antiretroviral therapy prior to admission, and 80% had a CD4 count less than 200.
      HIV-infected patients had a greater hospital mortality (50% vs 38%; p < 0.01).
      HIV infection (odds ratio = 1.78; p = 0.005) was an independent predictor of
      mortality by multivariate regression modeling after adjusting for age, history of
      pneumonia, history of hospital-acquired infection, and history of sepsis.
      CONCLUSIONS: HIV-infected patients with severe sepsis continue to suffer worse
      outcomes compared with HIV-uninfected patients in a large urban safety-net
      hospital caring for patients with limited access to medical care. Further studies
      need to be done to investigate the effect of socioeconomic status and mitigate
      healthcare disparities among critically ill HIV-infected patients.

PMID- 25853591
TI  - A Randomized Controlled Trial of Regional Citrate Versus Regional Heparin
      Anticoagulation for Continuous Renal Replacement Therapy in Critically Ill
      Adults.
AB  - OBJECTIVE: To determine whether regional anticoagulation of continuous renal
      replacement therapy circuits using citrate and calcium prolongs circuit life
      and/or affects circulating cytokine levels compared with regional anticoagulation
      using heparin and protamine. DESIGN: Multicenter, parallel group randomized
      controlled trial. SETTING: Seven ICUs in Australia and New Zealand. PATIENTS:
      Critically ill adults requiring continuous renal replacement therapy.
      INTERVENTIONS: Patients were randomized to receive one of two methods of regional
      circuit anticoagulation: citrate and calcium or heparin and protamine.
      MEASUREMENTS AND MAIN RESULTS: The primary outcome was functional circuit life
      measured in hours, assessed using repeated events survival analysis. In addition,
      we measured changes in interleukin-6, interleukin-8, and interleukin-10 blood
      levels. We randomized 212 subjects who were treated with 857 continuous renal
      replacement therapy circuits (median 2 circuits per patient [interquartile range,
      1-6], 390 in citrate group vs 467 in heparin group). The groups were well matched
      for baseline characteristics. Patients receiving regional continuous renal
      replacement therapy anticoagulation with heparin and protamine were more likely
      to experience circuit clotting than those receiving citrate and calcium (hazard
      ratio, 2.03 [1.36-3.03]; p < 0.0005; 857 circuits). The median lifespan of the
      first study circuit in each patient was 39.2 hours (95% CI, 32.1-48.0 hr) in the
      citrate and calcium group versus 22.8 hours (95% CI, 13.3-34.0 hr) in the heparin
      and protamine group (log rank p = 0.0037, 204 circuits). Circuit anticoagulation
      with citrate and calcium had similar effects on cytokine levels compared with
      heparin and protamine anticoagulation. There were more adverse events in the
      group assigned to heparin and protamine anticoagulation (11 vs 2; p = 0.011).
      CONCLUSIONS: Regional citrate and calcium anticoagulation prolongs continuous
      renal replacement therapy circuit life compared with regional heparin and
      protamine anticoagulation, does not affect cytokine levels, and is associated
      with fewer adverse events.

PMID- 25853592
TI  - Selenide Targets to Reperfusing Tissue and Protects It From Injury.
AB  - OBJECTIVES: Since blood selenium levels decrease after ischemia and reperfusion
      injury, and low blood selenium correlates with negative outcome, we designed and
      performed experiments to determine how selenium distribution is affected by
      ischemia reperfusion injury. Furthermore, we tested whether different chemical
      forms of selenium would affect outcome after ischemia and reperfusion injury. We
      also examined the metabolic effects of selenide administration. DESIGN:
      Laboratory investigation. SETTING: Animal research laboratory. SUBJECTS: Adult
      male C57BL/6 mice. INTERVENTIONS: To determine selenium localization, we
      administered tracer doses of radioactive selenium 75 in the form of selenite or
      selenide and measured blood and tissue selenium levels after ischemia and
      reperfusion injury. Anesthetized mice were subjected to myocardial ischemia
      reperfusion injury (coronary artery occlusion for 60 min followed by 5 min of
      reperfusion after occlusion was removed) or hindlimb ischemia reperfusion injury
      (left leg tourniquet for 90 min followed by 5 min reperfusion after tourniquet
      removal). To determine whether exogenous selenium administration could reduce
      ischemia reperfusion injury, we synthesized and administered sodium hydroselenide
      and sodium selenite solutions (0.05-2.4 mg/kg). Solutions were administered at
      the end of coronary artery occlusion but before reperfusion. In order to
      determine the metabolic effects of selenide administration, we exposed mice to
      hydrogen selenide gas (0-5 ppm) mixed into air (20.95% oxygen) for up to 3 hours.
      MEASUREMENTS AND MAIN RESULTS: In targeting assays, we measured blood and tissue
      selenium levels. We observed that blood selenium decreases after myocardial
      ischemia reperfusion and displays an inverse correlation with injury severity;
      selenium accumulation in heart correlates directly with injury severity. We also
      measured whether oxidized selenium, selenite, and reduced selenium, selenide,
      would target to injured heart tissue in myocardial ischemia reperfusion and
      injured leg muscle in a hindlimb model of ischemia reperfusion. Only selenide
      targets to injured tissue. We also measured damage after myocardial ischemia
      reperfusion injury using morphometry, neutrophil accumulation, blood cardiac
      troponin levels, and echocardiography and observed in all assays that selenide
      reduced damage to the heart; selenite was not effective. And finally, to assay
      metabolism, we measured oxygen consumption, carbon dioxide production, and body
      core temperature before, during, and after hydrogen selenide administration. All
      measurements indicate that selenide decreases metabolism. CONCLUSIONS: Selenide
      targets to reperfusing tissue and reduces reperfusion injury perhaps by affecting
      oxygen metabolism.

PMID- 25853594
TI  - Diversity goals in medicine: it's time to stop talking and start walking.

PMID- 25853593
TI  - Multiple photomorphogenic repressors work in concert to regulate Arabidopsis
      seedling development.
AB  - Light is both a source of energy and a critically important environmental signal
      for plant development. Through decades of research, 2 groups of photomorphogenic
      repressors have been identified. The first group is CONSTITUTIVE
      PHOTOMORPHOGENIC/DE-ETIOLATED/FUSCA (COP/DET/FUS), which were first identified by
      genetic screening and then by purification of protein complexes. Another group is
      the Phytochrome-Interacting Factors (PIFs), which were identified by yeast 2
      hybrid screens using phyB as bait. How so many factors work together to repress
      photomorphogenesis has long been an interesting question. Previously, we
      demonstrated that CULLIN4 (CUL4) works as a core factor connecting the COP1-SPA
      complexes, the COP9 signalosome (CSN), and the COP10-DDB1-DET1 (CDD) complex.
      Recently, we showed that DET1 represses photomorphogenesis through positively
      regulating the abundance of PIF proteins in the dark. Dr. Huq and his colleagues
      reported that PIFs may enhance the function of COP1-SPA complexes to promote the
      degradation of HY5, and thus they synergistically repress photomorphogenesis in
      the dark. Though much work still needs to be done, these recent breakthroughs
      shed light on the regulatory relationships among these multiple photomorphogenic
      repressors. 

PMID- 25853595
TI  - Poor representation of Blacks, Latinos, and Native Americans in medicine.
AB  - BACKGROUND AND OBJECTIVES: In this article, the authors discuss how various
      systems in medicine are limiting representation of blacks, Latinos, and Native
      Americans. Flat and decreasing percentages of Underrepresented Minorities in
      Medicine (URMM), especially in the black and Native American populations, is
      concerning for family medicine since members from URMM groups care for minority
      and underserved populations in greater numbers. Underrepresentation is not only
      noted in the medical community but also in our medical schools when it comes to
      numbers of URMM faculty. The changing definition of "disadvantaged" in medical
      school admissions has also played a part in limiting URMM representation. In
      addition, the Medical College Admissions Test (MCAT) excludes black, Latino, and
      Native American students in greater numbers. The authors support these arguments
      with evidence from the medical literature. Although unintentional, these systems
      effectively limit representation of blacks, Latinos, and Native Americans in
      medicine. Effective changes are suggested and can be implemented to ensure that
      URMM individuals have equal representation in careers in medicine.

PMID- 25853596
TI  - Trends in contraceptive and preconception care in United States ambulatory
      practices.
AB  - BACKGROUND AND OBJECTIVES: Since 2005, the Centers for Disease Control and
      Prevention (CDC), American Academy of Family Physicians (AAFP), and American
      College of Obstetricians and Gynecologists (ACOG) have recommended incorporating
      family planning and preconception counseling into routine primary care visits. We
      compared rates of reproductive health service provision to women aged 15--44
      years before and after these guidelines were issued and identified patient,
      physician, and visit characteristics associated with the likelihood of provision
      of preconception or contraceptive services. METHODS: The National Ambulatory
      Medical Care Survey (NAMCS) and the National Hospital Ambulatory Medical Care
      Survey (NHAMCS) collected nationally representative data on provision of
      preconception and contraceptive services in 1998--2000 and 2009--2010. We used
      multivariable logistic regression with appropriate survey weights to assess
      changes over time in provision of these services, while controlling for patient
      demographics, medical comorbidities, and physician or clinic specialty. RESULTS:
      Among ambulatory encounters with women of reproductive age, provision of
      reproductive health services increased from 9.5% to 14% between 1998--2000 and
      2009--2010, largely due to increased provision of prescription contraception.
      CONCLUSIONS: Despite CDC recommendations, a minority of ambulatory visits made by
      US women of reproductive age currently include either preconception or
      contraceptive services. Future work should focus on understanding barriers and
      developing interventions to facilitate incorporation of recommended services into
      primary care.

PMID- 25853597
TI  - The incorporation of stress management programming into family medicine
      residencies-results of a national survey of residency directors: a CERA study.
AB  - BACKGROUND AND OBJECTIVES: Residents' stress and burnout is a concern among
      family medicine residency programs. Our objective is to assess stress management
      options available to family medicine residents. METHODS: In 2012, the Council of
      Academic Family Medicine Educational Research Alliance (CERA) e-mailed a survey
      to US residency directors. Questions were asked on four types of stress
      management programming (SMP): (1) access to counselors, social workers, or mental
      health providers, (2) residency support or Balint groups, (3) stress management
      lectures or workshops, and (4) residency retreats. We assessed how many programs
      contained all four types of SMP and their relationship to the following topics:
      stress management techniques for patients, spirituality, mind/body techniques,
      and self-care for residents. RESULTS: Of the 212 responses, 29% reported having
      all four types of SMP. Eighty-three percent reported stress management lectures
      or workshops, and 79% reported residency retreats. Smaller and mid-size
      residencies (36%) and residencies in the West (36%) were more likely to have all
      four types of SMP. There was a correlation between having didactics, clinical
      rotations, and electives on stress management techniques for patient care and
      having stress management lectures or workshops for residents. There was
      statistical significance between having resident self-care curriculum and (1)
      having retreats and (2) stress management lectures or workshops. CONCLUSIONS: It
      is necessary to evaluate whether residency programs are providing appropriate
      stress management skills for residents that will improve physician wellness and
      patient outcomes.

PMID- 25853598
TI  - Pharmaceutical industry interactions in family medicine residencies decreased
      between 2008 and 2013: a CERA study.
AB  - BACKGROUND AND OBJECTIVES: Most medical residents have some interaction with the
      pharmaceutical industry. It is not known if this interaction has changed over
      time. We determined whether interactions between family medicine residencies and
      the pharmaceutical industry have changed in the past 5 years. METHODS: We
      surveyed program directors of US family medicine residencies with questions
      addressing industry-sponsored gifts, drug samples, access of industry
      representatives to trainees, and industry-sponsored residency activities. The
      questions were part of a larger 2013 survey administered by the Council of
      Academic Family Medicine Educational Research Alliance (CERA). The authors
      compared results from 2008 and 2013. RESULTS: The response rate to the 2013 CERA
      program director survey was 56% (251/445); 47% (208/445) of surveyed directors
      viewed and answered all survey questions. Between 2008 and 2013, residency
      programs that accept no gifts or industry-sponsored food increased from 48%
      (137/286) to 73% (151/208). Residencies refusing samples increased from 52%
      (148/286) to 78% (166/212), and residencies that do not allow industry
      representatives to have access to learners increased from 43% (124/286) to 74%
      (157/212). Residency programs that forbade industry-sponsored activities remained
      stable (67% versus 73%). About half (49%) (101/208)) of programs in 2013
      qualified as "pharma-free," compared to 26% (75/286) in 2008. CONCLUSIONS: In
      2013, one of two family medicine residencies disallow gifts, drug samples,
      interactions between residents and pharmaceutical sales representatives, and
      pharmaceutical industry-sponsored activities. This proportion is twice what was
      observed in 2008. Restrictions increased in all categories except industry
      sponsored activities.

PMID- 25853599
TI  - What physicians from diverse specialties know and support in health care reform.
AB  - BACKGROUND AND OBJECTIVES: The United States is in an unprecedented era of health
      care reform that is pushing medical professionals and medical educators to
      evaluate the future of their patients, careers, and the field of medicine. Our
      objectives were to describe physician familiarity and knowledge with the Patient
      Protection and Affordable Care Act (ACA) and to determine if knowledge is
      associated with support and endorsement of the ACA. METHODS: We used a cross
      sectional Internet-based survey of 559 physicians practicing in California.
      Primary outcomes were physician support and endorsement of ACA: (1) overall
      impact on the country (one item) and (2) perceived impact on physician's medical
      practice (one item). The primary predictor was knowledge of the ACA as measured
      with 10 questions. Other measures included age, gender, race-ethnicity,
      specialty, political views, provision of direct care, satisfaction with the
      practice of medicine, and compensation type. Descriptive statistics and multiple
      variable regression models were calculated. RESULTS: Respondents were 65%
      females, and the mean age was 54 years (+/- 9.7). Seventy-seven percent of
      physicians understood the ACA somewhat well/very well, and 59% endorsed the ACA,
      but 36% of physicians believed that health care reform will most likely hurt
      their practice. Primary care physicians were more likely to perceive that the new
      law will help their practice, compared to procedural specialties. Satisfaction
      with the practice of medicine, political affiliation, compensation type, and more
      knowledge of the health care law were independently associated with endorsement
      of the ACA. CONCLUSIONS: Endorsement of the ACA varied by specialty, knowledge,
      and satisfaction with the practice of medicine.

PMID- 25853600
TI  - The effect of dual accreditation on family medicine residency programs.
AB  - BACKGROUND AND OBJECTIVES: In 1985, the American Osteopathic Association (AOA)
      Board of Trustees agreed to allow residency programs to become dually accredited
      by the AOA and Accreditation Council for Graduate Medical Education (ACGME).
      Despite the increase in such programs, there has been minimal research comparing
      these programs to exclusively ACGME-accredited residencies. This study examines
      the association between dual accreditation and suggested markers of quality.
      METHODS: Standard characteristics such as regional location, program structure
      (community or university based), postgraduate year one (PGY-1) positions offered,
      and salary (PGY-1) were obtained for each residency program. In addition, the
      faculty to resident ratio in the family medicine clinic and the number of half
      days residents spent in the clinic each week were recorded. Initial Match rates
      and pass rates of new graduates on the ABFM examination from 2009 to 2013 were
      also obtained. Variables were analyzed using chi-square and Student's t test.
      Logistic regression models were then created to predict a program's 5-year
      aggregate initial Match rate and Board pass rate in the top tertile as compared
      to the lowest tertile. RESULTS: Dual accreditation was obtained by 117 (27.0%) of
      programs. Initial analyses revealed associations between dually accredited
      programs and mean year of initial ACGME program accreditation, regional location,
      program structure, tracks, and alternative medicine curriculum. When evaluated in
      logistic regression, dual accreditation status was not associated with Match
      rates or ABFM pass rates. CONCLUSIONS: By examining suggested markers of program
      quality for dually accredited programs in comparison to ACGME-only accredited
      programs, this study successfully established both differences and similarities
      among the two types.

PMID- 25853601
TI  - Collaboration versus competition: an interprofessional education experience.
AB  - BACKGROUND AND OBJECTIVES: Our purpose was to assess student, preceptor, and
      patient satisfaction with a phased pilot project to introduce interprofessional
      education teams into a clinical setting. METHODS: Focus groups with students and
      preceptors were used to evaluate acceptability with interprofessional education
      teams. We assessed pairings of second-year physician assistant students (PAS2)
      with both first- and second-year medical students (MS1, MS2) for three to eight
      clinic sessions in a university-based primary care clinic, over a period of 2
      years. RESULTS: Twenty students and seven preceptors participated in paired
      clinical placement. All students agreed that the pairing was helpful for their
      learning. MS felt that they benefitted from the clinical experience of the PAS,
      whereas PAS felt that MS brought depth of information from their didactic
      learning. All students wished that the clinic sessions could have been more
      frequent. Preceptors did not feel precepting two students was more burdensome
      than precepting one student but did feel it was important to choose appropriate
      students who were interested in working together and teaching each other.
      Preceptors felt that the MS2/PAS2 pairing was optimal. CONCLUSIONS: Students and
      preceptors were all satisfied with interprofessional teams in the clinical
      setting. This model provides one solution to the dilemma of multiple learners
      requiring training in a limited number of clinical placement sites.

PMID- 25853602
TI  - Teaching cross-cultural communication skills online: a multi-method evaluation.
AB  - BACKGROUND AND OBJECTIVES: Cultural competency education is an important and
      required part of undergraduate medical education. The objective of this study was
      to evaluate whether an online cross-cultural communication module could increase
      student use of cross-cultural communication questions that assess the patient's
      definition of the problem, the way the problem affects their life, their concerns
      about the problem, and what the treatment should be (PACT). METHODS: We used
      multi-method assessment of students assigned to family medicine clerkship blocks
      that were randomized to receive online cultural competency and PACT training
      added to their standard curriculum or to a control group receiving the standard
      curriculum only. Outcomes included comparison, via analysis of variance, of
      number of PACT questions used during an observed Standardized Patient Exercise,
      end-of-year OSCE scores, and qualitative analysis of student narratives. RESULTS:
      Students (n=119) who participated in the online module (n=60) demonstrated
      increased use of cross-cultural communication PACT questions compared to the
      control group (n=59) and generally had positive themes emerge from their
      reflective writing. The module had the biggest impact on students who later went
      on to match in high communication specialties. CONCLUSIONS: Online teaching of
      cross-cultural communication skills can be effective at changing medical student
      behavior.

PMID- 25853603
TI  - Longitudinal hyperlipidemia outcomes at three student-run free clinic sites.
AB  - BACKGROUND AND OBJECTIVES: Student-run free clinics (SRFC) aim to improve health
      outcomes of vulnerable populations by providing care to those who have difficulty
      accessing the traditional health care safety net. Reducing low density
      lipoprotein (LDL) is known to improve health outcomes, yet uninsured patients
      remain especially susceptible to poor control. This study describes
      hyperlipidemia control over time among patients who received care at three
      University of California San Diego Student-Run Free Clinic Project (SRFCP) sites.
      METHODS: The authors performed a retrospective review of clinic visits from
      August 2006--November 2010 from three sites of the SRFCP. Patients with a new
      diagnosis of hyperlipidemia, a baseline LDL level, and at least one follow-up LDL
      drawn between 6 weeks and 18 months were included in this study (n=96).
      Hyperlipidemia control was analyzed using descriptive statistics, Fisher's exact
      tests, paired t tests, and binary logistic regression. RESULTS: At the last
      visit, 58.3% (56/96) of patients had achieved LDL goal. LDL decreased from a
      baseline mean of 135.8 mg/dL to 101.3mg/dL among the cohort (P<.001). Statins
      were used in 86.5% (83/96) of patients. No significant differences were noted
      when stratified by language, gender, diabetes comorbidity, homelessness, or
      clinic site. When comparing Hispanics and Caucasians only, Hispanic patients had
      better LDL control than Caucasians. CONCLUSIONS: This study demonstrates that a
      SRFC can effectively manage hyperlipidemia over time, and rates of control can
      exceed national standards.

PMID- 25853604
TI  - A new way of hearing.

PMID- 25853605
TI  - Heart and kidney.

PMID- 25853606
TI  - Trends in patient encounters.

PMID- 25853607
TI  - Macrophage Migration Inhibitory Factor Deficiency Causes Prolonged Hearing Loss
      After Acoustic Overstimulation.
AB  - HYPOTHESIS: Macrophage migration inhibitory factor plays an important role in
      noise-induced hearing loss. BACKGROUND: Macrophage migration inhibitory factor is
      an essential factor in axis formation and neural development. Macrophage
      migration inhibitory factor is expressed in the inner ear, but its function
      remains to be elucidated. METHODS: Macrophage migration inhibitory factor
      deficient mice (MIF(-/-) mice) were used in this study. Wild-type and MIF(-/-)
      mice received noise exposure composed of octave band noise. Auditory brainstem
      response thresholds were examined before (control) and at 0, 12, and 24 hours and
      2 weeks after the intense noise exposure. Morphological findings of cochlear hair
      cells were investigated using scanning electron microscopy. Histopathological
      examination with hematoxylin and eosin staining and TUNEL assay were also
      performed. RESULTS: In both the wild-type and MIF(-/-) mice, acoustic
      overstimulation induced significant hearing loss compared with the control level.
      Two weeks after the intense noise exposure, the MIF(-/-) mice had an increased
      hearing threshold compared with the wild-type mice. Scanning electron microscopy
      demonstrated that the outer hair cells in the MIF(-/-) mice were affected 2 weeks
      after noise exposure compared with the wild-type mice. TUNEL-positive cells were
      identified in the organ of Corti of the MIF(-/-) mice. CONCLUSION: The MIF(-/-)
      mice had prolonged hearing loss and significant loss of cochlear hair cells after
      intense noise exposure. Macrophage migration inhibitory factor may play an
      important role in recovery from acoustic trauma. Management of macrophage
      migration inhibitory factor may be a novel therapeutic option for noise-induced
      hearing loss.

PMID- 25853608
TI  - Effects of Hand Placement Technique on the Video Head Impulse Test (vHIT) in
      Younger and Older Adults.
AB  - OBJECTIVE: To investigate the effects of hand placement techniques on the video
      head impulse test (vHIT) responses (i.e., gain, velocity) in older and younger
      adults and to determine intra-rater and inter-rater reliability of the horizontal
      vHIT. DESIGN: Descriptive, reliability study. SETTING: University research
      laboratory. SUBJECTS: Forty healthy adults grouped by age with negative history
      of current or previous vestibular diseases between the ages of 20 and 88 years
      (mean = 46.60, standard deviation 23.20). MAIN OUTCOME MEASURES: Three examiners
      each used two hand placement techniques (chin and head) to elicit the horizontal
      vHIT responses. Both the examiner and hand placement orders were counterbalanced
      to account for order and fatigue effects. The outcome measures of interest were
      vHIT gain and velocity. RESULTS: A two-way between-subject factorial analysis of
      variance revealed a significant main effect for hand placement technique and gain
      response. Mean values for vHIT gain were higher for head technique. Significant
      main effects were observed for the velocity response for hand placement technique
      and age group. Mean velocity values were higher for chin technique and lower
      velocities were observed in the older age group. Intra- and inter-rater
      reliability scores were consistent for gain values; however, poor to fair inter
      rater reliability scores were observed for velocity values. CONCLUSION: It is
      suggested that clinical sites select one hand placement technique for the measure
      to provide consistency of protocol. Establishing clinical norms using the one
      selected method to verify reliability within and across clinicians is suggested
      before examination with a disordered population.

PMID- 25853609
TI  - Manual Electrode Array Insertion Through a Robot-Assisted Minimal Invasive
      Cochleostomy: Feasibility and Comparison of Two Different Electrode Array
      Subtypes.
AB  - HYPOTHESIS: To evaluate the feasibility and the results of insertion of two types
      of electrode arrays in a robotically assisted surgical approach. BACKGROUND:
      Recent publications demonstrated that robot-assisted surgery allows the
      implantation of free-fitting electrode arrays through a cochleostomy drilled via
      a narrow bony tunnel (DCA). We investigated if electrode arrays from different
      manufacturers could be used with this approach. METHODS: Cone-beam CT imaging was
      performed on five-cadaveric heads after placement of fiducial screws. Relevant
      anatomical structures were segmented and the DCA trajectory, including the
      position of the cochleostomy, was defined to target the center of the scala
      tympani while reducing the risk of lesions to the facial nerve. Med-El Flex 28
      and Cochlear CI422 electrodes were implanted on both sides, and their position
      was verified by cone-beam CT. Finally, temporal bones were dissected to assess
      the occurrence of damage to anatomical structures during DCA drilling. RESULTS:
      The cochleostomy site was directed in the scala tympani in 9 of 10 cases. The
      insertion of electrode arrays was successful in 19 of 20 attempts. No facial
      nerve damage was observed. The average difference between the planned and the
      postoperative trajectory was 0.17 +/- 0.19 mm at the level of the facial nerve.
      The average depth of insertion was 305.5 +/- 55.2 and 243 +/- 32.1 degrees with
      Med-El and Cochlear arrays, respectively. CONCLUSIONS: Robot-assisted surgery is
      a reliable tool to allow cochlear implantation through a cochleostomy. Technical
      solutions must be developed to improve the electrode array insertion using this
      approach.

PMID- 25853610
TI  - Vestibular and Balance Impairment Contributes to Cochlear Implant Failure in
      Children.
AB  - OBJECTIVE: To determine the role of vestibular and balance dysfunction in
      children with cochlear implant (CI) failure. STUDY DESIGN: Retrospective case
      review. SETTING: Tertiary referral center. PATIENTS: Thirty-five children with CI
      failure were compared to 165 children who did not experience CI failure. MAIN
      OUTCOME MEASURES: Vestibular function was compared between groups by horizontal
      canal function (measured by caloric, rotational, video Head Impulse Testing
      [vHIT]), saccular function (vestibular evoked myogenic potentials [VEMP]), and
      balance (measured by Bruininks-Oseretsky Test [BOT-2]). RESULTS: Twenty-one
      patients completed vestibular and balance testing. Patients with CI failure
      demonstrated significantly more abnormal horizontal canal function than those who
      did not experience CI failure (caloric: 81 vs. 47%, p = 0.004; rotational/vHIT:
      71 vs. 35%, p = 0.001). Absence of bilateral horizontal canal function increased
      the odds of CI failure 7.6 times. A greater proportion of children with CI
      failure had abnormal saccular function compared to those without CI failure (81
      vs. 46%, p = 0.003). Children with CI failure had significantly worse balance
      (BOT-2 score: 7.8) than children who did not experience CI failure (BOT-2 score:
      12.2) (p < 0.0001). CONCLUSIONS: Vestibular end-organ dysfunction and its
      resulting balance impairment have been identified as important risk factors for
      CI failure in children. Early identification and treatment of such impairments
      may avoid or delay implant failures and prevent children from experiencing
      periods of sound deprivation that could impact speech and language acquisition.

PMID- 25853611
TI  - A Comparison Between Wireless CROS and Bone-anchored Hearing Devices for Single
      sided Deafness: A Pilot Study.
AB  - INTRODUCTION: This study compared wireless Contralateral Routing of Signals
      (CROS) hearing aid and bone-anchored hearing device (BAHD) in patients with
      single-sided deafness. METHODS: Eight adults with single-sided deafness
      previously implanted with a BAHD were given a 2-week trial with a CROS hearing
      aid and tested in unaided and aided conditions. Both devices were compared on
      head shadow effect reduction, speech perception measures in quiet and in noise,
      self-assessment questionnaires, and daily diaries. RESULTS: Both the CROS and
      BAHD significantly reduced the head shadow effect. QuickSIN scores were
      significantly better with noise presented to the poorer ear, as compared to the
      better ear, for the unaided condition, the BAHD, and the CROS. Scores showed no
      significant differences between the CROS and BAHD with noise presented to the
      better ear, but scores with the CROS were significantly poorer than in the
      unaided condition with noise presented to the poorer ear. There were no
      significant differences between BAHD and CROS for the ratings on the Bern Benefit
      in Single-Sided Deafness and Speech Spatial Qualities questionnaires. Both
      devices were worn an average of 10 hours per day. Four participants preferred the
      CROS for sound quality; three preferred the BAHD for comfort. CONCLUSION:
      Comparisons of CROS and BAHD need to be re-evaluated as both technologies have
      evolved. In our pilot study, both devices seem comparable, with the CROS avoiding
      the risks of surgery, and we recommend a trial of CROS in our center for first
      line treatment of single-sided deafness.

PMID- 25853612
TI  - Sudden Bilateral Hearing Loss After Cervical and Ocular Vestibular Evoked
      Myogenic Potentials.
AB  - OBJECTIVE: Cervical and ocular vestibular evoked myogenic potentials (cVEMPs and
      oVEMPs) are commonly used in evaluation of neurotologic disorders. We present a
      case of sudden bilateral hearing loss immediately after oVEMP and cVEMP testing.
      The hearing loss did not recover. To our knowledge, no previous case reports
      discuss sudden hearing loss, especially bilateral, associated with VEMP testing.
      PATIENT: A single patient with sudden bilateral hearing loss that has persisted
      after cVEMP and oVEMP. INTERVENTION: The patient had a history of chronic daily
      dizziness. She underwent vestibular function testing that included cVEMP and
      oVEMP testing. A significant bilateral sensorineural hearing loss was noted
      immediately after cVEMP and oVEMP testing and confirmed with audiometric testing.
      Despite the use of oral steroids, her hearing loss did not recover. MAIN OUTCOME
      MEASURES: Serial audiograms, calculated maximum total sound energies to each ear.
      RESULTS: Pre-VEMP versus post-VEMP audiograms show increased thresholds and
      decreased word recognition scores; total sound energy delivered to each ear shows
      significant sound exposure. CONCLUSION: Although VEMP testing is thought to be
      safe and well tolerated, a significant amount of sound can be delivered to the
      cochlea, and certain individuals may be susceptible to acoustic trauma at these
      levels. We recommend limits for VEMP stimuli levels and attention to total sound
      exposure when multiple trials are used.

PMID- 25853613
TI  - Long-term Compliance and Satisfaction With Percutaneous Bone Conduction Devices
      in Patients With Congenital Unilateral Conductive Hearing Loss.
AB  - OBJECTIVE: Patients with congenital unilateral conductive hearing loss (UCHL) can
      either be watchful monitored or treated surgically through the fitting of a
      percutaneous bone conduction device (BCD) or, in some cases, atresia repair. The
      current study evaluated the long-term compliance and satisfaction with a
      percutaneous BCD in this specific population. STUDY DESIGN: Fifty-three
      consecutive patients with congenital UCHL treated with a percutaneous BCD in our
      tertiary referral center between 1998 and 2011 were identified. Clinical and
      audiological data were retrospectively gathered from the patients' files. The
      patients were interviewed by telephone about their current device usage status
      and were asked to complete the Speech, Spatial and Qualities of Hearing Scale
      (SSQ). RESULTS: Compliance with the BCD was 56.6% after a mean follow-up of 7
      years. The mean age at implantation of the users (22 years) was significantly
      higher than that of the nonusers (10 years). The mean time of device usage before
      the patients stopped using the BCD was 5 years. The primary reasons mentioned for
      quitting the BCD were experiencing excess background noise and/or subjectively
      not receiving enough benefit. Objectively measured features of binaural
      processing affected by the BCD were found to correlate with long-term BCD usage.
      The SSQ revealed significant improvement in the aided condition compared with the
      nonaided condition in the users, in contrast to the nonusers. CONCLUSION: The
      current disappointing long-term compliance figures indicate the need for an even
      more careful and individualized approach with life-long follow-up when fitting
      BCDs in this specific population, especially in children.

PMID- 25853614
TI  - A Retrospective Analysis of the Contribution of Reported Factors in Cochlear
      Implantation on Hearing Preservation Outcomes.
AB  - INTRODUCTION: Preservation of residual hearing is essential to perceive acoustic
      stimulation from hybrid cochlear implants (CI). Preservation is a good marker of
      atraumatic surgery and residual hearing may be exploited further or enhanced in
      future therapies, making complete hearing preservation a desirable goal for all
      current CI surgeries. There is large variability in the amount of hearing
      preserved and the timeframe over which it is lost after CI. The increase in
      numbers of patients with high levels of residual hearing at implantation means
      that understanding the variables affecting its preservation is more important
      than ever. DATA SOURCES: An English search term with generic and specific items
      concerning hearing preservation and cochlear implantation was searched on the Web
      of Science service. The search timeframe was limited to 2000 to 2014, with no
      language limitations on results. STUDY SELECTION: Hearing preservation,
      retrospective CI outcome studies which reported pre- and post-surgical pure-tone
      audiometry (PTA) were identified and selected. DATA EXTRACTION: PTA thresholds
      were extracted from audiograms or tables and converted into a low-frequency
      hearing preservation (LFHP) score. Data for 21 factors associated with hearing
      preservation were collected from studies. DATA SYNTHESIS: Factors were included
      in a hearing preservation model if they had both a significant bivariate
      correlation with LFHP and a significant Kruskal-Wallis H test result (for ordinal
      data) or a significant multiple regression analysis result (for scale data).
      CONCLUSIONS: Seven factors were found to have a significant effect on hearing
      preservation: insertion site, progressive versus stable hearing loss, insertion
      angle of electrode, use of intraoperative topical steroids, use of steroids (via
      any route/timing), hearing etiology, and electrode array type. The best hearing
      preservation options are given.

PMID- 25853615
TI  - Analysis of Intraoperative Radiographic Electrode Placement During Cochlear
      Implantation.
AB  - OBJECTIVE: To investigate the clinical value of intraoperative plain radiographs
      in determining correct placement of cochlear implants. PATIENTS: All cochlear
      implant insertions over a 10-year period by a single surgeon. INTERVENTIONS:
      Cochlear implantation with intraoperative imaging. MAIN OUTCOME MEASURE: Whether
      intraoperative imaging affects clinical/surgical management. RESULTS: A
      consecutive retrospective review of 207 cochlear implantations performed in 187
      patients was performed. All implants performed had intraoperative plain film
      imaging. Etiology of hearing loss, surgical variations, gender, age, and implant
      type did not affect intraoperative imaging. Four cases were identified where
      variations in intraoperative imaging interpreted by the surgeon warranted further
      discussion. In one patient, the intraoperative x-ray interpretation missed an
      incorrectly placed electrode. Postoperative CT scan confirmed implant electrode
      within the superior semicircular canal. In three patients, intraoperative x-ray
      results aided management by confirming surgical findings; however, no subsequent
      clinical or surgical alterations were made based on imaging. One of these three
      patients experienced a noticeable function decline postoperatively that
      correlated with altered positioning of the cochlear implant on intraoperative
      radiographs. In all surgeries, no changes were made to the electrode placement
      based on the intraoperative radiographs. CONCLUSION: Intraoperative plain film
      imaging during cochlear implantation, although commonly employed, does not
      typically affect clinical management. For select cases, imaging may continue to
      be useful based on the surgeon's discretion and intraoperative findings for
      confirmatory purposes.

PMID- 25853617
TI  - The C-terminal heme regulatory motifs of heme oxygenase-2 are redox-regulated
      heme binding sites.
AB  - Heme oxygenase-2 (HO2), an enzyme that catalyzes the conversion of heme to
      biliverdin, contains three heme regulatory motifs (HRMs) centered at Cys127,
      Cys265, and Cys282. Previous studies using the soluble form of human HO2 spanning
      residues 1-288 (HO2sol) have shown that a disulfide bond forms between Cys265 and
      Cys282 and that, in this oxidized state, heme binds to the catalytic site of
      HO2sol via His45. However, various mutational and spectroscopic studies have
      confirmed the involvement of cysteine in Fe(3+)-heme binding upon reduction of
      the disulfide bond. In an effort to understand how the HRMs are involved in
      binding of heme to disulfide-reduced HO2sol, in the work described here, we
      further investigated the properties of Fe(3+)-heme bound to HO2. Specifically, we
      investigated binding of Fe(3+)-heme to a truncated form of soluble HO2 (residues
      213-288; HO2tail) that spans the C-terminal HRMs of HO2 but lacks the catalytic
      core. We found that HO2tail in the disulfide-reduced state binds Fe(3+)-heme and
      accounts for the spectral features observed upon binding of heme to the disulfide
      reduced form of HO2sol that cannot be attributed to heme binding at the catalytic
      site. Further analysis revealed that while HO2sol binds one Fe(3+)-heme per
      monomer of protein under oxidizing conditions, disulfide-reduced HO2sol binds
      slightly more than two. Both Cys265 and Cys282 were identified as Fe(3+)-heme
      ligands, and His256 also acts as a ligand to the Cys265-ligated heme.
      Additionally, Fe(3+)-heme binds with a much weaker affinity to Cys282 than to
      Cys265, which has an affinity much weaker than that of the His45 binding site in
      the catalytic core. In summary, disulfide-reduced HO2 has multiple binding sites
      with varying affinities for Fe(3+)-heme.

PMID- 25853616
TI  - An examination of speech reception thresholds measured in a simulated reverberant
      cafeteria environment.
AB  - OBJECTIVE: There is increasing demand in the hearing research community for the
      creation of laboratory environments that better simulate challenging real-world
      listening environments. The hope is that the use of such environments for testing
      will lead to more meaningful assessments of listening ability, and better
      predictions about the performance of hearing devices. Here we present one
      approach for simulating a complex acoustic environment in the laboratory, and
      investigate the effect of transplanting a speech test into such an environment.
      DESIGN: Speech reception thresholds were measured in a simulated reverberant
      cafeteria, and in a more typical anechoic laboratory environment containing
      background speech babble. STUDY SAMPLE: The participants were 46 listeners
      varying in age and hearing levels, including 25 hearing-aid wearers who were
      tested with and without their hearing aids. RESULTS: Reliable SRTs were obtained
      in the complex environment, but led to different estimates of performance and
      hearing-aid benefit from those measured in the standard environment. CONCLUSIONS:
      The findings provide a starting point for future efforts to increase the real
      world relevance of laboratory-based speech tests.

PMID- 25853618
TI  - Biomimetic synthesis of two salmahyrtisanes: salmahyrtisol A and hippospongide A.
AB  - Sesterterpenes with a salmahyrtisane skeleton have been synthesized for the first
      time. (-)-Sclareol has been selected as a precursor for the synthesis of two
      novel natural products: salmahyrtisol A (1) and hippospongide A (2). Our results
      represent a biomimetic approach to obtaining salmahyrtisanes from hyrtiosanes.
      Salmahyrtisol A has shown an activity comparable to that of the standard
      anticancer drugs in the cell lines A549, HBL-100, HeLa, and SW1573. 

PMID- 25853619
TI  - Salmonella ghosts expressing enterotoxigenic Escherichia coli k88ab, k88ac, k99,
      and fasa fimbrial antigens induce robust immune responses in a mouse model.
AB  - BACKGROUND: Bacterial ghosts can be developed as safe and effective vaccines
      against bacterial infectious disease such as enterotoxigenic Escherichia coli
      (ETEC)-induced diarrhea in neonatal piglets. OBJECTIVE: Immune responses against
      a Salmonella ghost expressing ETEC K88ab, K88ac, K99, and FasA antigens with
      various adjuvants and inoculation routes were evaluated in mice. ANIMALS AND
      METHODS: A ghost cell expressing K88ab, K88ac, K99, and FasA fimbrial antigens of
      ETEC on the envelope of ?asd Salmonella typhimurium was constructed as a
      candidate vaccine against ETEC infection. To optimize the immunization strategy,
      6-week-old female BALB/c mice were inoculated with the ghost and various
      adjuvants, and the immune responses against the individual fimbrial antigens were
      measured. Blood samples from caudal vein to evaluate serum IgG concentrations and
      fecal samples to evaluate mucosal IgA concentrations were collected up to 14
      weeks post-prime immunization. RESULTS: All groups with single, double, and
      triple inoculations of the ghost showed higher humoral and mucosal immune
      responses than the control group. In particular, the groups with intramuscular
      double and triple inoculations showed significantly higher immune responses. In
      addition, oral inoculation with a combination of the ghost and MONTANIDE IMS 1113
      (MI1113) resulted in high and prolonged induction of intestinal IgA levels.
      CONCLUSION: These results indicated that both systemic and mucosal immunity
      against ETEC fimbrial antigens expressed by the ghost are induced by
      intramuscular booster inoculation with the ghost, and that addition of M1113 to
      the ghost was found to result in prominent induction of mucosal immunity through
      oral inoculation.

PMID- 25853622
TI  - Errata.

PMID- 25853623
TI  - HLA-A, HLA-B, and HLA-DRB1 Allele and Haplotype Frequencies in Renal Transplant
      Candidates in a Population in Southern Brazil.
AB  - BACKGROUND: Very few studies have examined the diversity of human leukocyte
      antigens (HLA) in the Brazilian renal transplant candidates. METHODS: The
      frequencies of the HLA-A, HLA-B, and HLA-DRB1 alleles, haplotypes and phenotypes
      were studied in 522 patients with chronic renal failure, renal transplant
      candidates, registered at the Transplant Centers in north/northwestern Parana
      State, southern Brazil. Patients were classified according to the ethnic group
      (319 whites [Caucasians], 134 mestizos [mixed race descendants of Europeans,
      Africans, and Amerindians; browns or "pardos"] and 69 blacks). The HLA typing was
      performed by the polymerase chain reaction sequence-specific oligonucleotide
      method (PCR-SSO), combined with Luminex technology. RESULTS: In the analysis of
      the total samples, 20 HLA-A, 32 HLA-B, and 13 HLA-DRB1 allele groups were
      identified. The most frequent allele groups for each HLA locus were HLA-A*02
      (25.4%), HLA-B*44 (10.9%), and HLA-DRB1*13 (13.9%). The most frequent haplotypes
      were HLA-A*01-B*08-DRB1*03 (2.3%), A*02-B*44-DRB1*07 (1.2%), and A*03-B*07
      DRB1*11 (1.0%). Significant differences (P < 0.05) were observed in the HLA-A*68,
      B*08, and B*58 allele frequencies among ethnic groups. CONCLUSIONS: This study
      provides the first data on the HLA-A, HLA-B, and HLA-DRB1 allele, phenotype and
      haplotype frequencies of renal transplant candidates in a population in southern
      Brazil.

PMID- 25853625
TI  - A ruthenium complex as a single-component redox shuttle for electrochemical
      photovoltaics.
AB  - A primitive version of a ruthenium complex [Ru(bpy)3(2+)] was employed for the
      first time as a new conceptual "single-component redox shuttle" for dye
      sensitized solar cells. This single shuttle led to a large enhancement of the
      open-circuit photovoltage (VOC) to ~940 mV relative to that of conventional
      iodine-based shuttle and greatly increased the efficiency of the solar-to
      electric energy conversion at lower illumination levels by a factor of ca. 5.6. 

PMID- 25853624
TI  - IFNbeta secreted by microglia mediates clearance of myelin debris in CNS
      autoimmunity.
AB  - INTRODUCTION: Multiple sclerosis (MS) is a chronic demyelinating disorder of the
      central nervous system (CNS) leading to progressive neurological disability.
      Interferon beta (IFNbeta) represents a standard treatment for relapsing-remitting
      MS and exogenous administration of IFNbeta exhibits protective effects in
      experimentally induced CNS autoimmunity. Also, genetic deletion of IFNbeta in
      mice leads to an aggravation of disease symptoms in the MS model of experimental
      autoimmune encephalomyelitis (EAE). However, neither the underlying mechanisms
      mediating the beneficial effects nor the cellular source of IFNbeta have been
      fully elucidated. RESULTS: In this report, a subpopulation of activated microglia
      was identified as the major producers of IFNbeta in the CNS at the peak of EAE
      using an IFNbeta-fluorescence reporter mouse model. These IFNbeta expressing
      microglia specifically localized to active CNS lesions and were associated with
      myelin debris in demyelinated cerebellar organotypic slice cultures (OSCs). In
      response to IFNbeta microglia showed an enhanced capacity to phagocytose myelin
      in vitro and up-regulated the expression of phagocytosis-associated genes.
      IFNbeta treatment was further sufficient to stimulate association of microglia
      with myelin debris in OSCs. Moreover, IFNbeta-producing microglia mediated an
      enhanced removal of myelin debris when co-transplanted onto demyelinated OSCs as
      compared to IFNbeta non-producing microglia. CONCLUSIONS: These data identify
      activated microglia as the major producers of protective IFNbeta at the peak of
      EAE and as orchestrators of IFNbeta-induced clearance of myelin debris.

PMID- 25853626
TI  - The Use of Tilted Implant for Posterior Atrophic Maxilla.
AB  - PURPOSE: To retrospectively analyze the influence of implant inclination on
      marginal bone loss at freestanding implant-supported fixed partial prostheses
      (FPPs) over a medium-term period of functional loading. MATERIALS AND METHODS:
      Twenty-nine partially edentulous patients with freestanding FPDs supported by two
      implants placed in a two-stage procedure comprised the study group. The anterior
      implant was placed axially, and the posterior tilted distally. Mesial or distal
      inclination of each implant was measured in relation to the vertical axis
      perpendicular to the occlusal plane. Average bone loss was compared between
      straight and tilted implants, smokers, and nonsmokers. RESULTS: Mean angulation
      of the anterior axial-positioned implant was 3.45 degrees distally (range 0-8)
      and of the distal implants was 32.83 degrees distally (range 20-50 degrees).
      Average bone loss after 1, 3, and 5 years was 0.89 (SD = 0.73), 1.18 (SD = 0.74),
      and 1.50 (SD = 0.81), respectively, for axial implants, and 0.98 (SD = 0.69),
      1.10 (SD = 0.60) and 1.50 (SD = 0.67) for tilted implants, with no significant
      correlation between implant angulation and bone loss. A significant correlation
      between implant angulation and annual bone loss was obtained for tilted implants
      only (r = 0.52, p = .004).Using Albrektsson criteria, the success rate was 89.6%
      (26 out of 29 implants) for straight and 93.1% (27 out of 29) for tilted
      implants. CONCLUSION: The study demonstrates no effect of implant angulation on
      peri-implant bone loss in the posterior maxilla.

PMID- 25853627
TI  - Stress-related anhedonia is associated with ventral striatum reactivity to reward
      and transdiagnostic psychiatric symptomatology.
AB  - BACKGROUND: Early life stress (ELS) is consistently associated with increased
      risk for subsequent psychopathology. Individual differences in neural response to
      reward may confer vulnerability to stress-related psychopathology. Using data
      from the ongoing Duke Neurogenetics Study, the present study examined whether
      reward-related ventral striatum (VS) reactivity moderates the relationship
      between retrospectively reported ELS and anhedonic symptomatology. We further
      assessed whether individual differences in reward-related VS reactivity were
      associated with other depressive symptoms and problematic alcohol use via stress
      related anhedonic symptoms and substance use-associated coping. METHOD: Blood
      oxygen level-dependent functional magnetic resonance imaging (fMRI) was collected
      while participants (n = 906) completed a card-guessing task, which robustly
      elicits VS reactivity. ELS, anhedonic symptoms, other depressive symptoms, coping
      behavior, and alcohol use behavior were assessed with self-report questionnaires.
      Linear regressions were run to examine whether VS reactivity moderated the
      relationship between ELS and anhedonic symptoms. Structural equation models
      examined whether this moderation was indirectly associated with other depression
      symptoms and problematic alcohol use through its association with anhedonia.
      RESULTS: Analyses of data from 820 participants passing quality control
      procedures revealed that the VS * ELS interaction was associated with anhedonic
      symptoms (p = 0.011). Moreover, structural equation models indirectly linked this
      interaction to non-anhedonic depression symptoms and problematic alcohol use
      through anhedonic symptoms and substance-related coping. CONCLUSIONS: These
      findings suggest that reduced VS reactivity to reward is associated with
      increased risk for anhedonia in individuals exposed to ELS. Such stress-related
      anhedonia is further associated with other depressive symptoms and problematic
      alcohol use through substance-related coping.

PMID- 25853629
TI  - Learning from instructional explanations: effects of prompts based on the active
      constructive-interactive framework.
AB  - Although instructional explanations are commonly provided when learners are
      introduced to new content, they often fail because they are not integrated into
      effective learning activities. The recently introduced active-constructive
      interactive framework posits an effectiveness hierarchy in which interactive
      learning activities are at the top; these are then followed by constructive and
      active learning activities, respectively. Against this background, we combined
      instructional explanations with different types of prompts that were designed to
      elicit these learning activities and tested the central predictions of the active
      constructive-interactive framework. In Experiment 1, N = 83 students were
      randomly assigned to one of four combinations of instructional explanations and
      prompts. To test the active < constructive learning hypothesis, the learners
      received either (1) complete explanations and engaging prompts designed to elicit
      active activities or (2) explanations that were reduced by inferences and
      inference prompts designed to engage learners in constructing the withheld
      information. Furthermore, in order to explore how interactive learning activities
      can be elicited, we gave the learners who had difficulties in constructing the
      prompted inferences adapted remedial explanations with either (3) unspecific
      engaging prompts or (4) revision prompts. In support of the active < constructive
      learning hypothesis, we found that the learners who received reduced explanations
      and inference prompts outperformed the learners who received complete
      explanations and engaging prompts. Moreover, revision prompts were more effective
      in eliciting interactive learning activities than engaging prompts. In Experiment
      2, N = 40 students were randomly assigned to either (1) a reduced explanations
      and inference prompts or (2) a reduced explanations and inference prompts plus
      adapted remedial explanations and revision prompts condition. In support of the
      constructive < interactive learning hypothesis, the learners who received adapted
      remedial explanations and revision prompts as add-ons to reduced explanations and
      inference prompts acquired more conceptual knowledge. 

PMID- 25853628
TI  - KRAS oncogene repression in colon cancer cell lines by G-quadruplex binding
      indolo[3,2-c]quinolines.
AB  - KRAS is one of the most frequently mutated oncogenes in human cancer, yet
      remaining undruggable. To explore a new therapeutic strategy, a library of 5
      methyl-indolo[3,2-c]quinoline derivatives (IQc) with a range of alkyldiamine side
      chains was designed to target DNA and RNA G-quadruplexes (G4) in the promoter and
      5'-UTR mRNA of the KRAS gene. Biophysical experiments showed that di-substituted
      IQc compounds are potent and selective KRAS G4 stabilizers. They preferentially
      inhibit the proliferation of KRAS mutant cancer cell lines (0.22 < IC50 < 4.80
      MUM), down-regulate KRAS promoter activity in a luciferase reporter assay, and
      reduce both KRAS mRNA and p21(KRAS) steady-state levels in mutant KRAS colon
      cancer cell lines. Additionally, IQcs induce cancer cell death by apoptosis,
      explained in part by their capacity to repress KRAS expression. Overall, the
      results suggest that targeting mutant KRAS at the gene level with G4 binding
      small molecules is a promising anticancer strategy. 

PMID- 25853630
TI  - Residual metallic contamination of transferred chemical vapor deposited graphene.
AB  - Integration of graphene with Si microelectronics is very appealing by offering a
      potentially broad range of new functionalities. New materials to be integrated
      with the Si platform must conform to stringent purity standards. Here, we
      investigate graphene layers grown on copper foils by chemical vapor deposition
      and transferred to silicon wafers by wet etching and electrochemical delamination
      methods with respect to residual submonolayer metallic contaminations. Regardless
      of the transfer method and associated cleaning scheme, time-of-flight secondary
      ion mass spectrometry and total reflection X-ray fluorescence measurements
      indicate that the graphene sheets are contaminated with residual metals (copper,
      iron) with a concentration exceeding 10(13) atoms/cm(2). These metal impurities
      appear to be partially mobile upon thermal treatment, as shown by depth profiling
      and reduction of the minority charge carrier diffusion length in the silicon
      substrate. As residual metallic impurities can significantly alter electronic and
      electrochemical properties of graphene and can severely impede the process of
      integration with silicon microelectronics, these results reveal that further
      progress in synthesis, handling, and cleaning of graphene is required to advance
      electronic and optoelectronic applications. 

PMID- 25853631
TI  - Simultaneous imaging of Zn(2+) and Cu(2+) in living cells based on DNAzyme
      modified gold nanoparticle.
AB  - Trace Zn(2+) and Cu(2+) in living cells play important roles in the regulation of
      biological function. It is significant to simultaneously detect the cellular
      Zn(2+) and Cu(2+). Here, we present a novel two-color fluorescence nanoprobe
      based on the DNAzymes for simultaneous imaging of Zn(2+) and Cu(2+) in living
      cells. The probe consists of a 13 nm gold nanoparticle, DNAzymes that are
      specific for Zn(2+) and Cu(2+), and the substrate strands labeled with
      fluorophores at the 5' end and quenchers at the 3' end. The fluorescence of the
      fluoreophores is quenched both by the gold nanoparticle and the quencher. After
      the nanoprobes are transferred into the cells, the substrate strands would be
      cleaved in the presence of the Zn(2+) and Cu(2+) target, resulting in
      disassociation of the shorter DNA fragments containing fluorophores, which
      produce fluorescence signals correlated with the location and concentration of
      the Zn(2+) and Cu(2+). The nanoprobe exhibits high specificity, nuclease
      stability, and good biocompatibility. Moreover, the nanoprobe can simultaneously
      monitor the cellular Zn(2+) and Cu(2+) with an on-site manner, providing the
      information on localization and concentration of targets, which is significant to
      further research the Zn(2+)- and Cu(2+)-relative cellular events and biological
      process. The proposed method has shown great potential in the detection of
      multiple metal ions in living cells, which may help us to better understand the
      function of metal ions in the fields of biochemistry, molecular biology, and
      cellular toxicology. 

PMID- 25853632
TI  - Vitamin D3 analogs for the treatment of osteoporosis.
AB  - Vitamin D supplementation is recommended whenever patients are given therapeutic
      drugs for osteoporosis, to make their calcium (Ca) balance positive. Vitamin D is
      converted to 25-hydroxyvitamin D in the liver, and then activated to become
      1alpha,25-dihydroxyvitamin D in the kidneys. The active vitamin D acts in the
      intestine to stimulate Ca absorption and maintain the Ca balance. 2beta-(3
      Hydroxypropyloxy)-1alpha,25-dihydroxyvitamin D3 (eldecalcitol) and 2-methylene-19
      nor-(20S)-1alpha,25-dihydroxyvitamin D3 (2MD) are newly developed vitamin D
      analogs, with a substitution at the 2 position of 1alpha,25-dihydroxyvitamin D3
      (calcitriol). Eldecalcitol and 2MD share common structural and biological
      characteristics. Both compounds increase serum Ca levels more markedly than
      calcitriol, increase bone mineral density (BMD), and improve bone strength in
      ovariectomized (OVX) rats. In a randomized, placebo-controlled, double-blind, 1
      year clinical trial, eldecalcitol dose-dependently increased lumbar and hip BMD
      and suppressed bone turnover markers in patients with osteoporosis. Whereas, 2MD
      markedly increased the bone turnover markers, but it did not change the BMD of
      postmenopausal women with osteopenia in a 1 year clinical trial. After a
      randomized, double-blind, 3 year fracture-prevention trial comparing it with
      alfacalcidol, eldecalcitol was approved for the treatment of osteoporosis in
      Japan. On the other hand, the manufacturer discontinued the clinical development
      of 2MD. In this review, we discuss the similarities and differences between these
      2 compounds, and the reasons why different outcomes resulted from their clinical
      trials.

PMID- 25853633
TI  - A Survey of Experts Regarding the Treatment of Adult Vulvar Lichen Sclerosus.
AB  - OBJECTIVE: The objective of this work was to survey physician members and fellows
      of the International Society for the Study of Vulvovaginal Disease to determine
      current expert opinion regarding the management of adult vulvar lichen sclerosus.
      MATERIALS AND METHODS: A cross-sectional design was used. An electronic survey
      was emailed to all members and fellows of the International Society for the Study
      of Vulvovaginal Disease. Responses were analyzed using univariate methods.
      Subgroup analyses were performed to report treatment differences between
      gynecologists and dermatologists and between physicians in the United States and
      Europe. RESULTS: In total, 128 (42%) of 305 providers responded to the survey.
      Analysis was confined to the 114 physician respondents who treat patients with
      lichen sclerosus. Clobetasol propionate 0.05% is the most common first-line agent
      used in lichen sclerosus (85%). The most common second-line agents used are
      tacrolimus (39%), other topical steroids (28%), and intralesional steroids (13%).
      Most physicians (59%) start all patients with lichen sclerosus on drug therapy at
      an initial visit, regardless of symptoms. Dermatologists are more likely to treat
      all patients (both symptomatic and asymptomatic) than gynecologists (p < .01).
      Most physicians (64%) continue maintenance therapy in all patients. Gynecologists
      are more likely than dermatologists to treat only when patients are symptomatic
      versus using maintenance therapy (p = .03). Physicians practicing in the United
      States are more likely than those practicing in Europe to treat all patients with
      maintenance therapy (p < .01). CONCLUSIONS: Lichen sclerosus management varies
      among experts. Variations exist between physician specialties and between those
      practicing in different geographic locations. Uncertainty regarding optimal
      treatment remains, especially regarding long-term management.

PMID- 25853634
TI  - Vulvodynia and Concomitant Femoro-Acetabular Impingement: Long-Term Follow-up
      After Hip Arthroscopy.
AB  - OBJECTIVE: We hypothesized that in patients with vulvodynia and femoro-acetabular
      impingement (FAI), vulvar pain may be generated by the effect of FAI on pelvic
      floor structures, and treatment with arthroscopy may improve vulvodynia. We also
      sought to identify characteristics of patients whose vulvodynia improved after
      arthroscopy. MATERIALS AND METHODS: A case series of patients with vulvodynia and
      FAI underwent physical therapy, and, if hip symptoms did not improve,
      arthroscopy. Three to 5 years postoperatively, follow-up of outcomes after
      arthroscopy on vulvodynia was performed using chart review and patient
      questionnaire. Clinical characteristics and pain scores describing patients with
      and without vulvodynia improvement were assessed. RESULTS: Twenty-six patients
      with generalized unprovoked vulvodynia (GUV) or clitorodynia underwent
      arthroscopy for FAI. Six patients, all younger than 30 years, experienced lasting
      improvement in vulvodynia. Twenty patients, with an older mean age, longer mean
      vulvodynia duration, and mainly severe pain scores, did not experience vulvar
      pain improvement after arthroscopy. CONCLUSION: This case series describes
      improved vulvodynia outcomes after arthroscopy for FAI in women younger than 30
      years. Patients with vulvar pain and coexisting FAI had GUV and clitorodynia.

PMID- 25853635
TI  - Highly aging-resistant elastomers doped with antioxidant-loaded clay nanotubes.
AB  - A novel aging-resistant styrene-butadiene rubber (SBR) composite is prepared
      using the antioxidant N-isopropyl-N'-phenyl-p-phenylenediamine (4010NA) loaded
      inside of halloysite clay nanotubes and used as filler. Loading the antioxidant
      inside of halloysite allows for its sustained release for nine months in the
      rubber matrix. By utilizing modified halloysite, the antioxidant concentration in
      this rubber nanoformulation is tripled without causing "blooming" defects.
      Furthermore, the halloysite is silanized to enhance its miscibility with rubber.
      The aging resistance of SBR-halloysite composites is studied by comparing the
      mechanical properties before and after thermal-oxidative aging. A seven-day test
      at 90  degrees C shows preservation of mechanical properties, and no 4010NA
      blooming is observed, even after one month. Styrene-butadiene rubber with 27 wt %
      halloysite loaded with 4010NA shows marked increase in aging resistance and
      promising future of halloysite as a functional rubber filler. 

PMID- 25853637
TI  - Mapsnp: an R package to plot a genomic map for single nucleotide polymorphisms.
AB  - Single-nucleotide polymorphism (SNP) is one of the most common sources of genetic
      variations of the genome. Currently, SNPs are a main target for most genetic
      association studies. Visualizing genomic coordinates of SNPs, including their
      physical location relative to their host gene, and the structure of the relevant
      transcripts, may provide intuitive supplements to the understanding of their
      functions. Nevertheless, to date, no such easy-to-use programming tools exist.
      Therefore, we developed an R package, "mapsnp", to plot genomic map for a panel
      of SNPs within a genome region of interest, including the relative chromosome
      location and the transcripts in the region. mapsnp is a simple and flexible
      software package which can be used to visualize a genomic map for SNPs,
      integrating a chromosome ideogram, genomic coordinates, SNP locations and SNP
      labels. 

PMID- 25853636
TI  - Regional Strain Analysis with Multidetector CT in a Swine Cardiomyopathy Model:
      Relationship to Cardiac MR Tagging and Myocardial Fibrosis.
AB  - PURPOSE: To investigate the use of cine multidetector computed tomography (CT) to
      detect changes in myocardial function in a swine cardiomyopathy model. MATERIALS
      AND METHODS: All animal protocols were in accordance with the Principles for the
      Utilization and Care of Vertebrate Animals Used in Testing Research and Training
      and approved by the University of Missouri Animal Care and Use Committee. Strain
      analysis of cine multidetector CT images of the left ventricle was optimized and
      analyzed with feature-tracking software. The standard of reference for strain was
      harmonic phase analysis of tagged cardiac magnetic resonance (MR) images at 3.0
      T. An animal model of cardiomyopathy was imaged with both cardiac MR and 320
      section multidetector CT at a temporal resolution of less than 50 msec. Three
      groups were evaluated: control group (n = 5), aortic-banded myocardial
      hypertrophy group (n = 5), and aortic-banded and cyclosporine A- treated
      cardiomyopathy group (n = 5). Histologic samples of the myocardium were obtained
      for comparison with strain results. Dunnett test was used for comparisons of the
      concentric remodeling group and eccentric remodeling group against the control
      group. RESULTS: Collagen volume fraction ranged from 10.9% to 14.2%; lower
      collagen fraction values were seen in the control group than in the
      cardiomyopathy groups (P < .05). Ejection fraction and conventional metrics
      showed no significant differences between control and cardiomyopathy groups.
      Radial strain for both cardiac MR and multidetector CT was abnormal in both
      concentric (cardiac MR 25.1% +/- 4.2; multidetector CT 28.4% +/- 2.8) and
      eccentric (cardiac MR 23.2% +/- 2.0; multidetector CT 24.4% +/- 2.1) remodeling
      groups relative to control group (cardiac MR 18.9% +/- 1.9, multidetector CT
      22.0% +/- 1.7, P < .05, all comparisons). Strain values for multidetector CT
      versus cardiac MR showed better agreement in the radial direction than in the
      circumferential direction (r = 0.55, P = .03 vs r = 0.40, P = .13, respectively).
      CONCLUSION: Multidetector CT strain analysis has potential to identify regional
      wall-motion abnormalities in cardiomyopathy that is not otherwise detected using
      conventional metrics of myocardial function.

PMID- 25853638
TI  - Copper-Catalyzed Radical/Radical C(sp 3)-H/P-H Cross-Coupling: alpha
      Phosphorylation of Aryl Ketone O-Acetyloximes.
AB  - The selective radical/radical cross-coupling of two different organic radicals is
      a great challenge due to the inherent activity of radicals. In this paper, a
      copper-catalyzed radical/radical C(sp 3)-H/P-H cross-coupling has been developed.
      It provides a radical/radical cross-coupling in a selective manner. This work
      offers a simple way toward beta-ketophosphonates by oxidative coupling of aryl
      ketone o-acetyloximes with phosphine oxides using CuCl as catalyst and PCy3 as
      ligand in dioxane under N2 atmosphere at 130  degrees C for 5 h, and yields
      ranging from 47% to 86%. The preliminary mechanistic studies by electron
      paramagnetic resonance (EPR) showed that, 1) the reduction of ketone o
      acetyloximes generates iminium radicals, which could isomerize to alpha-sp(3) 
      carbon radical species; 2) phosphorus radicals were generated from the oxidation
      of phosphine oxides. Various aryl ketone o-acetyloximes and phosphine oxides were
      suitable for this transformation.

PMID- 25853639
TI  - Quantifying Insulin Therapy Requirements to Preserve Islet Graft Function
      Following Islet Transplantation.
AB  - A mathematical nonlinear regression model of several parameters (baseline insulin
      intake, posttransplant 2-h postprandial blood glucose, and stimulated C-peptide)
      from type 1 diabetics with HbA1c <6.5% who do not require insulin therapy and
      have no hypoglycemic instances was developed for accurately predicting
      supplemental insulin requirements in the posttransplant period. An insulin
      deficit threshold of 0.018 U/kg/day was defined as the average first-year
      calculated insulin deficit (CID), above which HbA1c rose to >6.5% during year 2
      of the posttransplant period. When insulin-untreated subjects were divided into
      two groups based on whether the average CID was smaller (group I) or greater
      (group II) than the insulin deficit threshold, HbA1c was found to be similar in
      the two groups in year 1, but increased significantly in group II to above 6.5%
      (with mean glucose of 121.9 mg/dl) but remained below 6.5% in group I subjects
      (with mean glucose of 108.7 mg/dl) in year 2 of the follow-up period. The greater
      insulin deficit in group II was also associated with a higher susceptibility to
      hyperglycemia during periods of low serum Rapamune and Prograf levels (combined
      levels below 11.2 and 4.7 ng/ml, respectively). Although the differences between
      predicted insulin requirement (PIR) and actual empirical insulin intake in the
      insulin-treated subjects were generally small, they were nonetheless sufficient
      to identify over- and underinsulinization at each follow-up visit for all
      subjects (n = 14 subjects, 135 observations). The newly developed model can
      effectively identify underinsulinized islet transplant recipients at risk for
      graft dysfunction due to inadequate supplemental insulin intake or those
      potentially susceptible to graft function loss due to inadequate
      immunosuppression. While less common following islet cell therapy, the model can
      also identify overinsulinized subjects who may be at risk for hypoglycemia.

PMID- 25853640
TI  - Surface-confined heterometallic triads on the basis of terpyridyl complexes and
      design of molecular logic gates.
AB  - Surface-confined heterometallic molecular triads (SURHMTs) were fabricated on
      SiOx-based solid substrates using optically rich and redox-active Fe-, Os-, and
      Ru-based terpyridyl complexes as metalloligands and Cu(2+) ions as linkers.
      Optical and electrochemical studies reveal efficient electronic intramolecular
      communication in these assemblies. The UV-vis spectra of the triads exhibit a
      superposition of the metal-to-ligand charge-transfer bands of individual
      complexes, providing a significant enlargement of the optical window, useful for
      application. Similarly, cyclic voltammograms of SURHMT layers show a variety of
      redox peaks corresponding to individual complexes as well as multi-redox states
      at a low potential. Interaction of a representative SURHMT assembly with redox
      active NOBF4 was investigated and used as a basis for configuring molecular logic
      gates. 

PMID- 25853642
TI  - Prologue: transformational healing solutions.
AB  - In recent years, the provision of wound care for patients has dramatically
      improved through the development of new therapeutic options, allowing for a wide
      range of wound care therapy choices. In June 2014, an educational International
      Surgical Wound Forum (ISWF) was held to present current options in wound care to
      a multidisciplinary group of healthcare providers. Topics included negative
      pressure wound therapy with instillation and dwell time (NPWTi-d), surgical
      incision management (SIM), use of NPWT in the management of the open abdomen,
      epidermal skin harvesting, and advanced wound dressings. This supplement provides
      in-depth discussion of some of the topics covered at the 2014 ISWF. 

PMID- 25853643
TI  - Innovation and wound healing.
AB  - Innovation in medicine requires unique partnerships between academic research,
      biotech or pharmaceutical companies, and health-care providers. While innovation
      in medicine has greatly increased over the past 100 years, innovation in wound
      care has been slow, despite the fact that chronic wounds are a global health
      challenge where there is a need for technical, process and social innovation.
      While novel partnerships between research and the health-care system have been
      created, we still have much to learn about wound care and the wound-healing
      processes. 

PMID- 25853644
TI  - The evolution of negative pressure wound therapy: negative pressure wound therapy
      with instillation.
AB  - Complex wounds pose a considerable burden to patients and the health-care system.
      The development of negative pressure wound therapy (NPWT) has revolutionised the
      treatment of these wounds. NPWT helps create a favourable wound healing
      environment by removing infectious material, decreasing oedema and promoting
      perfusion and granulation tissue formation. Additionally, NPWT has been reported
      to help reduce time to wound closure and length of hospital stay. Modifications
      of this foundation of wound care have added intermittent instillation with a
      dwell time to NPWT (NPWTi-d). This new system offers more comprehensive wound
      care through automated wound irrigation, allowing more control over the wound
      environment and the opportunity to deliver topical wound solutions directly to
      the affected tissues. A comparison between the two therapies, NPWT and NPWTi-d,
      is described, and two real-world applications of NPWTi-d are presented. 

PMID- 25853645
TI  - Incisional negative pressure wound therapy for high-risk wounds.
AB  - With an ageing population and a growing number of people with obesity and/or
      undergoing advanced cancer therapies, there is an increasing risk of surgical
      site complications including surgical site infections (SSIs). Postoperative
      shifting of large mobilised tissue flaps, such as in abdominoplasties, remains a
      dreaded complication, particularly following massive weight loss. Besides
      negative implications for the patient, surgical site complications result in an
      economic burden due to prolonged and repeated wound treatments. Preventative
      tools to reduce SSIs are needed. In selected patients at high risk of SSI and/or
      wound breakdown, use of incisional NPWT has been shown to actively manage clean,
      closed surgical incisions. This article contains a review of scientific and
      clinical research relevant to incisional NPWT use over surgical incisions, with
      particular emphasis on the common problem of wound breakdown and SSI following
      body-contouring surgery in post-bariatric patients. Although there are a growing
      number of studies describing use of incisional NPWT in a variety of applications,
      including vascular, cardiac and orthopaedic, a literature search revealed few
      studies regarding incisional NPWT use post body-contouring surgery. In a clinical
      study of seroma formation, less seroma and haematoma formation was reported in
      post-bariatric patients who received incisional NPWT, versus the control,
      following body-contouring surgery. In another study of widely applied external
      NPWT wound dressings over the ventral and lateral trunk following post-bariatric
      abdominal dermolipectomy, results showed a significant reduction in exudate
      formation, earlier drain removal, and decreased length of hospitalisation,
      compared with conventional treatment. Additional controlled studies are needed to
      validate the clinical impact of incisional NPWT following body-contouring
      surgery, and to determine proper recommendations for its use. 

PMID- 25853646
TI  - Use of epidermal grafts in wounds: a review of an automated epidermal harvesting
      system.
AB  - Chronic wounds continue to present a significant challenge to health-care
      providers across the globe. Unlike acute wounds, chronic wounds do not proceed
      through an orderly process of repair. In recent years, a number of wound healing
      treatments, such as dermal replacement scaffolds and negative pressure wound
      therapy, have promoted wound healing by stimulating the formation of granulation
      tissue. However, until recently there were few modalities designed to promote
      epithelialisation of a fully granulated wound. Split-thickness skin grafts
      (STSGs) have long been the gold standard for the management of acute wounds, but
      have not gained favour in the treatment of chronic wounds for several reasons:
      discomfort associated with the donor site, the creation of a second wound (donor
      site) in a patient with poor wound-healing potential, and a lack of documented
      efficacy for the procedure. Epidermal grafting does not have some of the
      limitations encountered with STSG; however, it has not gained wide acceptance, as
      previous harvesting techniques were cumbersome and time-consuming. A novel
      automated epidermal harvesting system, CelluTome Epidermal Harvesting System
      (KCI, an Acelity company, San Antonio, TX, USA), was commercially introduced in
      2013. The system yields up to 128 epidermal micrografts that can be easily
      harvested at the bedside without anaesthesia and transferred to the recipient
      site. The harvesting technique and the use of epidermal grafts in wounds are
      reviewed here. 

PMID- 25853647
TI  - Non-healing foot ulcers in diabetic patients: general and local interfering
      conditions and management options with advanced wound dressings.
AB  - Medical knowledge about wound management has improved as recent studies have
      investigated the healing process and its biochemical background. Despite this,
      foot ulcers remain an important clinical problem, often resulting in costly,
      prolonged treatment. A non-healing ulcer is also a strong risk factor for major
      amputation. Many factors can interfere with wound healing, including the
      patient's general health status (i.e., nutritional condition indicated by albumin
      levels) or drugs such as steroids that can interfere with normal healing.
      Diabetic complications (i.e., renal insufficiency) may delay healing and account
      for higher amputation rates observed in diabetic patients under dialysis
      treatment. Wound environment (e.g., presence of neuropathy, ischaemia, and
      infection) may significantly influence healing by interfering with the
      physiological healing cascade and adding local release of factors that may worsen
      the wound. The timely and well-orchestrated release of factors regulating the
      healing process, observed in acute wounds, is impaired in non-healing wounds that
      are blocked in a chronic inflammatory phase without progressing to healing. This
      chronic phase is characterised by elevated protease activity (EPA) of
      metalloproteinases (MMPs) and serine proteases (e.g., human neutrophil elastase)
      that interfere with collagen synthesis, as well as growth factor release and
      action. EPA (mainly MMP 9, MMP-8 and elastase) and inflammatory factors present
      in the wound bed (such as IL-1, IL-6, and TNFa) account for the catabolic state
      of non-healing ulcers. The availability of wound dressings that modulate EPA has
      added new therapeutic options for treating non-healing ulcers. The literature
      confirms advantages obtained by reducing protease activity in the wound bed, with
      better outcomes achieved by using these dressings compared with traditional ones.
      New technologies also allow a physician to know the status of the wound bed
      environment, particularly EPA, in a clinical setting. These may be helpful in
      guiding a clinician's options in treating very difficult-to-heal ulcers. 

PMID- 25853648
TI  - Analysis of Cell-Surface Receptor Dynamics through Covalent Labeling by Catalyst
      Tethered Antibody.
AB  - A general technique for introducing biophysical probes into selected receptors in
      their native environment is valuable for the study of their structure, dynamics,
      function, and molecular interactions. A number of such techniques rely on genetic
      engineering, which is not applicable for the study of endogenous proteins, and
      such approaches often suffer from artifacts due to the overexpression and bulky
      size of the probes/protein tags used. Here we designed novel catalyst-antibody
      conjugates capable of introducing small chemical probes into receptor proteins
      such as epidermal growth factor receptor (EGFR) and human epidermal growth factor
      receptor 2 (HER2) in a selective manner on the surface of living cells. Because
      of the selectivity and efficiency of this labeling technique, we were able to
      monitor the cellular dynamics and lifetime of HER2 endogenously expressed on
      cancer cells. More significantly, the current labeling technique comprises a
      stable covalent bond, which combined with a peptide mass fingerprinting analysis
      allowed epitope mapping of antibodies on living cells and identification of
      potential binding sites of anti-EGFR affibody. Although as yet unreported in the
      literature, the binding sites predicted by our labeling method were consistently
      supported by the subsequent mutation and binding assay experiments. In addition,
      this covalent labeling method provided experimental evidence that HER2 exhibits a
      more dynamic structure than expected on the basis of crystallographic analysis
      alone. Our novel catalyst-antibody conjugates are expected to provide a general
      tool for investigating the protein trafficking, fluctuation, and molecular
      interactions of an important class of cell-surface receptors on live cell
      surfaces. 

PMID- 25853650
TI  - Temperature Dependence of the Proteome Profile of the Psychrotolerant Pathogenic
      Food Spoiler Bacillus weihenstephanensis Type Strain WSBC 10204.
AB  - Bacillus weihenstephanensis is a subspecies of the Bacillus cereus sensu lato
      group of spore-forming bacteria known to cause food spoilage or food poisoning.
      The key distinguishing phenotype of B. weihenstephanensis is its ability to grow
      below 7  degrees C or, from a food safety perspective, to grow and potentially
      produce toxins in a refrigerated environment. Comparison of the proteome profile
      of B. weihenstephanensis upon its exposure to different culturing conditions can
      reveal clues to the mechanistic basis of its psychrotolerant phenotype as well as
      elucidate relevant aspects of its toxigenic profile. To this end, the genome of
      the type strain B. weihenstephanensis WSBC 10204 was sequenced and annotated.
      Subsequently, the proteome profiles of cells grown at either 6 or 30  degrees C
      were compared, which revealed considerable differences and indicated several
      hundred (uncharacterized) proteins as being subproteome- and/or temperature
      specific. In this manner, several processes were newly indicated to be dependent
      on growth temperature, such as varying carbon flux routes and a different role
      for the urea cycle. Furthermore, a possible post-translational regulatory
      function for acetylation was suggested. Toxin production was determined to be
      largely independent of growth temperature. 

PMID- 25853649
TI  - Target-dependent enrichment of virions determines the reduction of high
      throughput sequencing in virus discovery.
AB  - Viral infections cause many different diseases stemming both from well
      characterized viral pathogens but also from emerging viruses, and the search for
      novel viruses continues to be of great importance. High-throughput sequencing is
      an important technology for this purpose. However, viral nucleic acids often
      constitute a minute proportion of the total genetic material in a sample from
      infected tissue. Techniques to enrich viral targets in high-throughput sequencing
      have been reported, but the sensitivity of such methods is not well established.
      This study compares different library preparation techniques targeting both DNA
      and RNA with and without virion enrichment. By optimizing the selection of intact
      virus particles, both by physical and enzymatic approaches, we assessed the
      effectiveness of the specific enrichment of viral sequences as compared to non
      enriched sample preparations by selectively looking for and counting read
      sequences obtained from shotgun sequencing. Using shotgun sequencing of total DNA
      or RNA, viral targets were detected at concentrations corresponding to the
      predicted level, providing a foundation for estimating the effectiveness of
      virion enrichment. Virion enrichment typically produced a 1000-fold increase in
      the proportion of DNA virus sequences. For RNA virions the gain was less
      pronounced with a maximum 13-fold increase. This enrichment varied between the
      different sample concentrations, with no clear trend. Despite that less
      sequencing was required to identify target sequences, it was not evident from our
      data that a lower detection level was achieved by virion enrichment compared to
      shotgun sequencing. 

PMID- 25853651
TI  - Molten Au/Ge alloy migration in Ge nanowires.
AB  - Herein, we report time-resolved in situ transmission electron microscopy
      observation of Au particle melting at a Ge nanowire tip, subsequent forming of
      Au/Ge alloy liquid, and its migrating within the Ge nanowire. The migration
      direction and position of the Au/Ge liquid can be controlled by the applied
      voltage and the migration speed shows a linear deceleration in the nanowire. In a
      migration model proposed, the relevant dynamic mechanisms (electromigration,
      thermodiffusion, and viscous force, etc.) are discussed in detail. This work
      associated with the liquid mass transport in the solid nanowires should provide
      new insights into the crystal growth, interface engineering, and fabrication of
      the heterogeneous nanostructure-based devices. 

PMID- 25853652
TI  - DGEclust: differential expression analysis of clustered count data.
AB  - We present a statistical methodology, DGEclust, for differential expression
      analysis of digital expression data. Our method treats differential expression as
      a form of clustering, thus unifying these two concepts. Furthermore, it
      simultaneously addresses the problem of how many clusters are supported by the
      data and uncertainty in parameter estimation. DGEclust successfully identifies
      differentially expressed genes under a number of different scenarios, maintaining
      a low error rate and an excellent control of its false discovery rate with
      reasonable computational requirements. It is formulated to perform particularly
      well on low-replicated data and be applicable to multi-group data. DGEclust is
      available at http://dvav.github.io/dgeclust/. 

PMID- 25853653
TI  - Cerebrospinal fluid cytokine profiles predict risk of early mortality and immune
      reconstitution inflammatory syndrome in HIV-associated cryptococcal meningitis.
AB  - Understanding the host immune response during cryptococcal meningitis (CM) is of
      critical importance for the development of immunomodulatory therapies. We
      profiled the cerebrospinal fluid (CSF) immune-response in ninety patients with
      HIV-associated CM, and examined associations between immune phenotype and
      clinical outcome. CSF cytokine, chemokine, and macrophage activation marker
      concentrations were assayed at disease presentation, and associations between
      these parameters and microbiological and clinical outcomes were examined using
      principal component analysis (PCA). PCA demonstrated a co-correlated CSF cytokine
      and chemokine response consisting primarily of Th1, Th2, and Th17-type cytokines.
      The presence of this CSF cytokine response was associated with evidence of
      increased macrophage activation, more rapid clearance of Cryptococci from CSF,
      and survival at 2 weeks. The key components of this protective immune-response
      were interleukin (IL)-6 and interferon-gamma, IL-4, IL-10 and IL-17 levels also
      made a modest positive contribution to the PC1 score. A second component of co
      correlated chemokines was identified by PCA, consisting primarily of monocyte
      chemotactic protein-1 (MCP-1) and macrophage inflammatory protein-1alpha (MIP
      1alpha). High CSF chemokine concentrations were associated with low peripheral
      CD4 cell counts and CSF lymphocyte counts and were predictive of immune
      reconstitution inflammatory syndrome (IRIS). In conclusion CSF cytokine and
      chemokine profiles predict risk of early mortality and IRIS in HIV-associated CM.
      We speculate that the presence of even minimal Cryptococcus-specific Th1-type
      CD4+ T-cell responses lead to increased recruitment of circulating lymphocytes
      and monocytes into the central nervous system (CNS), more effective activation of
      CNS macrophages and microglial cells, and faster organism clearance; while high
      CNS chemokine levels may predispose to over recruitment or inappropriate
      recruitment of immune cells to the CNS and IRIS following peripheral immune
      reconstitution with ART. These results provide a rational basis for future
      studies of immune modulation in CM, and demonstrate the potential of baseline
      immune profiling to identify CM patients most at risk of mortality and subsequent
      IRIS. 

PMID- 25853654
TI  - Immune protection against Trypanosoma cruzi induced by TcVac4 in a canine model.
AB  - Chagas disease, caused by Trypanosoma cruzi, is endemic in southern parts of the
      American continent. Herein, we have tested the protective efficacy of a DNA
      prime/T. rangeli-boost (TcVac4) vaccine in a dog (Canis familiaris) model. Dogs
      were immunized with two-doses of DNA vaccine (pcDNA3.1 encoding TcG1, TcG2, and
      TcG4 antigens plus IL-12- and GM-CSF-encoding plasmids) followed by two doses of
      glutaraldehyde-inactivated T. rangeli epimastigotes (TrIE); and challenged with
      highly pathogenic T. cruzi (SylvioX10/4) isolate. Dogs given TrIE or empty
      pcDNA3.1 were used as controls. We monitored post-vaccination and post-challenge
      infection antibody response by an ELISA, parasitemia by blood analysis and
      xenodiagnosis, and heart function by electrocardiography. Post-mortem anatomic
      and pathologic evaluation of the heart was conducted. TcVac4 induced a strong IgG
      response (IgG2>IgG1) that was significantly expanded post-infection, and moved to
      a nearly balanced IgG2/IgG1 response in chronic phase. In comparison, dogs given
      TrIE or empty plasmid DNA only developed high IgG titers with IgG2 predominance
      in response to T. cruzi infection. Blood parasitemia, tissue parasite foci,
      parasite transmission to triatomines, electrocardiographic abnormalities were
      significantly lower in TcVac4-vaccinated dogs than was observed in dogs given
      TrIE or empty plasmid DNA only. Macroscopic and microscopic alterations, the
      hallmarks of chronic Chagas disease, were significantly decreased in the
      myocardium of TcVac4-vaccinated dogs. We conclude that TcVac4 induced immunity
      was beneficial in providing resistance to T. cruzi infection, evidenced by
      control of chronic pathology of the heart and preservation of cardiac function in
      dogs. Additionally, TcVac4 vaccination decreased the transmission of parasites
      from vaccinated/infected animals to triatomines. 

PMID- 25853655
TI  - Agreement between clinical history method, Orbscan IIz, and Pentacam in
      estimating corneal power after myopic excimer laser surgery.
AB  - The purpose of this study was to investigate the agreement between the clinical
      history method (CHM), Orbscan IIz, and Pentacam in estimating corneal power after
      myopic excimer laser surgery. Fifty five patients who had myopic LASIK/PRK were
      recruited into this study. One eye of each patient was randomly selected by a
      computer-generated process. At 6 months after surgery, postoperative corneal
      power was calculated from the CHM, Orbscan IIz total optical power at the 3.0 and
      4.0 mm zones, and Pentacam equivalent keratometric readings (EKRs) at 3.0, 4.0,
      and 4.5 mm. Statistical analyses included multilevel models, Pearson's
      correlation test, and Bland-Altman plots. The Orbscan IIz 3.0-mm and 4.0 mm total
      optical power, and Pentacam 3.0-mm, 4.0-mm, and 4.5-mm EKR values had strong
      linear positive correlations with the CHM values (r = 0.90-0.94, P = <0.001, for
      all comparisons, Pearson's correlation). However, only Pentacam 3.0-mm EKR was
      not statistically different from CHM (P = 0.17, multilevel models). The mean 3.0-
      and 4.0-mm total optical powers of the Orbscan IIz were significantly flatter
      than the values derived from CHM, while the average EKRs of the Pentacam at 4.0
      and 4.5 mm were significantly steeper. The mean Orbscan IIz 3.0-mm total optical
      power was the lowest keratometric reading compared to the other 5 values. Large
      95% LoA was observed between each of these values, particularly EKRs, and those
      obtained with the CHM. The width of the 95% LoA was narrowest for Orbscan IIz 3.0
      mm total optical power. In conclusion, the keratometric values extracted from
      these 3 methods were disparate, either because of a statistically significant
      difference in the mean values or moderate agreement between them. Therefore, they
      are not considered equivalent and cannot be used interchangeably. 

PMID- 25853656
TI  - Automated detection of soma location and morphology in neuronal network cultures.
AB  - Automated identification of the primary components of a neuron and extraction of
      its sub-cellular features are essential steps in many quantitative studies of
      neuronal networks. The focus of this paper is the development of an algorithm for
      the automated detection of the location and morphology of somas in confocal
      images of neuronal network cultures. This problem is motivated by applications in
      high-content screenings (HCS), where the extraction of multiple morphological
      features of neurons on large data sets is required. Existing algorithms are not
      very efficient when applied to the analysis of confocal image stacks of neuronal
      cultures. In addition to the usual difficulties associated with the processing of
      fluorescent images, these types of stacks contain a small number of images so
      that only a small number of pixels are available along the z-direction and it is
      challenging to apply conventional 3D filters. The algorithm we present in this
      paper applies a number of innovative ideas from the theory of directional
      multiscale representations and involves the following steps: (i) image
      segmentation based on support vector machines with specially designed multiscale
      filters; (ii) soma extraction and separation of contiguous somas, using a
      combination of level set method and directional multiscale filters. We also
      present an approach to extract the soma's surface morphology using the 3D
      shearlet transform. Extensive numerical experiments show that our algorithms are
      computationally efficient and highly accurate in segmenting the somas and
      separating contiguous ones. The algorithms presented in this paper will
      facilitate the development of a high-throughput quantitative platform for the
      study of neuronal networks for HCS applications. 

PMID- 25853657
TI  - Ecological drivers of shark distributions along a tropical coastline.
AB  - As coastal species experience increasing anthropogenic pressures there is a
      growing need to characterise the ecological drivers of their abundance and
      habitat use, and understand how they may respond to changes in their environment.
      Accordingly, fishery-independent surveys were undertaken to investigate shark
      abundance along approximately 400 km of the tropical east coast of Australia.
      Generalised linear models were used to identify ecological drivers of the
      abundance of immature blacktip Carcharhinus tilstoni/Carcharhinus limbatus,
      pigeye Carcharhinus amboinensis, and scalloped hammerhead Sphyrna lewini sharks.
      Results indicated general and species-specific patterns in abundance that were
      characterised by a range of abiotic and biotic variables. Relationships with
      turbidity and salinity were similar across multiple species, highlighting the
      importance of these variables in the functioning of communal shark nurseries. In
      particular, turbid environments were especially important for all species at
      typical oceanic salinities. Mangrove proximity, depth, and water temperature were
      also important; however, their influence varied between species. Ecological
      drivers may promote spatial diversity in habitat use along environmentally
      heterogeneous coastlines and may therefore have important implications for
      population resilience. 

PMID- 25853658
TI  - Colloidal Silver: Dangerous and Readily Available.

PMID- 25853660
TI  - Percutaneous ultrasound guided implantation of VX2 for creation of a rabbit
      hepatic tumor model.
AB  - Creation of a VX2 tumor model has traditionally required a laparotomy and
      surgical implantation of tumor fragments. Open surgical procedures are invasive
      and require long procedure times and recovery that can result in post-operative
      morbidity and mortality. The purpose of this study is to report the results of a
      percutaneous ultrasound guided method for creation of a VX2 model in rabbit
      livers. A total of 27 New Zealand white rabbits underwent a percutaneous
      ultrasound guided approach, where a VX2 tumor fragment was implanted in the
      liver. Magnetic resonance imaging was used to assess for tumor growth and
      necropsy was performed to determine rates of tract seeding and metastatic
      disease. Ultrasound guided tumor implantation was successful in all 27 rabbits.
      One rabbit died 2 days following the implantation procedure. Two rabbits had no
      tumors seen on follow-up imaging. Therefore, tumor development was seen in 24/26
      (92%) rabbits. During the follow-up period, tract seeding was seen in 8% of
      rabbits and 38% had extra-hepatic metastatic disease. Therefore, percutaneous
      ultrasound guided tumor implantation safely provides reliable tumor growth for
      establishing hepatic VX2 tumors in a rabbit model with decreased rates of tract
      seeding, compared to previously reported methods. 

PMID- 25853662
TI  - Ivermectin cream (Soolantra) for rosacea.

PMID- 25853661
TI  - Dose-dependent ATP depletion and cancer cell death following calcium
      electroporation, relative effect of calcium concentration and electric field
      strength.
AB  - BACKGROUND: Electroporation, a method for increasing the permeability of
      membranes to ions and small molecules, is used in the clinic with
      chemotherapeutic drugs for cancer treatment (electrochemotherapy).
      Electroporation with calcium causes ATP (adenosine triphosphate) depletion and
      cancer cell death and could be a novel cancer treatment. This study aims at
      understanding the relationship between applied electric field, calcium
      concentration, ATP depletion and efficacy. METHODS: In three human cell lines-
      H69 (small-cell lung cancer), SW780 (bladder cancer), and U937 (leukaemia),
      viability was determined after treatment with 1, 3, or 5 mM calcium and eight 99
      MUs pulses with 0.8, 1.0, 1.2, 1.4 or 1.6 kV/cm. Fitting analysis was applied to
      quantify the cell-killing efficacy in presence of calcium. Post-treatment
      intracellular ATP was measured in H69 and SW780 cells. Post-treatment
      intracellular ATP was observed with fluorescence confocal microscopy of
      quinacrine-labelled U937 cells. RESULTS: Both H69 and SW780 cells showed dose
      dependent (calcium concentration and electric field) decrease in intracellular
      ATP (p<0.05) and reduced viability. The 50% effective cell kill was found at 3.71
      kV/cm (H69) and 3.28 kV/cm (SW780), reduced to 1.40 and 1.15 kV/cm (respectively)
      with 1 mM calcium (lower EC50 for higher calcium concentrations). Quinacrine
      fluorescence intensity of calcium-electroporated U937 cells was one third lower
      than in controls (p<0.0001). CONCLUSIONS: Calcium electroporation dose
      dependently reduced cell survival and intracellular ATP. Increasing extracellular
      calcium allows the use of a lower electric field. GENERAL SIGNIFICANCE: This
      study supports the use of calcium electroporation for treatment of cancer and
      possibly lowering the applied electric field in future trials.

PMID- 25853663
TI  - Advice for travelers.

PMID- 25853664
TI  - In brief: severe bradycardia with sofosbuvir and amiodarone.

PMID- 25853659
TI  - Genetically determined height and coronary artery disease.
AB  - BACKGROUND: The nature and underlying mechanisms of an inverse association
      between adult height and the risk of coronary artery disease (CAD) are unclear.
      METHODS: We used a genetic approach to investigate the association between height
      and CAD, using 180 height-associated genetic variants. We tested the association
      between a change in genetically determined height of 1 SD (6.5 cm) with the risk
      of CAD in 65,066 cases and 128,383 controls. Using individual-level genotype data
      from 18,249 persons, we also examined the risk of CAD associated with the
      presence of various numbers of height-associated alleles. To identify putative
      mechanisms, we analyzed whether genetically determined height was associated with
      known cardiovascular risk factors and performed a pathway analysis of the height
      associated genes. RESULTS: We observed a relative increase of 13.5% (95%
      confidence interval [CI], 5.4 to 22.1; P<0.001) in the risk of CAD per 1-SD
      decrease in genetically determined height. There was a graded relationship
      between the presence of an increased number of height-raising variants and a
      reduced risk of CAD (odds ratio for height quartile 4 versus quartile 1, 0.74;
      95% CI, 0.68 to 0.84; P<0.001). Of the 12 risk factors that we studied, we
      observed significant associations only with levels of low-density lipoprotein
      cholesterol and triglycerides (accounting for approximately 30% of the
      association). We identified several overlapping pathways involving genes
      associated with both development and atherosclerosis. CONCLUSIONS: There is a
      primary association between a genetically determined shorter height and an
      increased risk of CAD, a link that is partly explained by the association between
      shorter height and an adverse lipid profile. Shared biologic processes that
      determine achieved height and the development of atherosclerosis may explain some
      of the association. (Funded by the British Heart Foundation and others.).

PMID- 25853665
TI  - Acute Influences of Bisphenol A Exposure on Hypothalamic Release of Gonadotropin
      Releasing Hormone and Kisspeptin in Female Rhesus Monkeys.
AB  - Bisphenol A (BPA) is an industrial compound with pervasive distribution in the
      environments of industrialized countries. The U.S. Centers for Disease Control
      recently found that greater than 90% of Americans carry detectable levels of BPA,
      raising concern over the direct influences of this compound on human physiology.
      Epidemiologic evidence links elevated BPA serum concentrations to human
      reproductive dysfunction, although controlled studies on the acute effect of BPA
      exposure on reproductive function are limited, particularly in primates. We
      evaluated the effect of direct BPA exposure on female primate hypothalamic
      peptide release. Specifically, using a microdialysis method, we examined the
      effects of BPA (0.1, 1, and 10nM) directly infused to the stalk-median eminence
      on the release of GnRH and kisspeptin (KP) in mid to late pubertal ovarian intact
      female rhesus monkeys. We found that the highest level of BPA exposure (10nM)
      suppressed both GnRH and KP release, whereas BPA at lower concentrations (0.1 and
      1nM) had no apparent effects. In addition, we measured BPA in plasma and
      hypothalamic dialysates after an iv bolus injection of BPA (100 MUg/kg). We found
      a relatively stable distribution of BPA between the blood and brain (plasma:brain
      ? 5:1) persists across a wide range of blood BPA concentrations (1-620 ng/mL).
      Findings of this study suggest that persistent, high-level exposures to BPA could
      impair female reproductive function by directly influencing hypothalamic
      neuroendocrine function. 

PMID- 25853666
TI  - The Effects of High-Fat Diet Exposure In Utero on the Obesogenic and Diabetogenic
      Traits Through Epigenetic Changes in Adiponectin and Leptin Gene Expression for
      Multiple Generations in Female Mice.
AB  - Recent studies demonstrate that epigenetic changes under malnutrition in utero
      might play important roles in transgenerational links with metabolic diseases. We
      have previously shown that exposure to a high-fat diet (HFD) in utero may cause a
      metabolic syndrome-like phenomenon through epigenetic modifications of
      Adiponectin and Leptin genes. Because an association of obesity between mother
      and offspring endured in multiple generations, we examined whether HFD exposure
      in utero might affect the metabolic status of female offspring through
      multigenerational epigenetic changes of Adiponectin and Leptin genes and whether
      a normal diet in utero for multiple generations might abolish such epigenetic
      changes after exposure to a HFD in utero using ICR mice. We observed that the
      effect of maternal HFD on offspring over multiple generations in metabolic
      syndrome-like phenomenon such as weight and fat mass gain, glucose intolerance,
      hypertriglyceridemia, abnormal adiponectin and leptin levels, and hypertension,
      were accumulated with expression and epigenetic changes in Adiponectin and Leptin
      genes. A normal diet in utero in the subsequent generations after HFD exposure in
      utero diminished, and a normal diet in utero for 3 generations completely
      abolished, the effect of HFD in utero on weight and fat mass gain, insulin
      resistance, serum triglyceride, adiponectin, and leptin levels, with epigenetic
      changes of Adiponectin and Leptin genes. Exposure to a HFD in utero might affect
      glucose and lipid metabolism of female offspring through epigenetic modifications
      to Adiponectin and Leptin genes for multiple generations. Obesogenic and
      diabetogenic traits were abolished after a maternal normal diet for 3
      generations. 

PMID- 25853668
TI  - Correction: an integrative computational approach for prioritization of genomic
      variants.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0114903.]. 

PMID- 25853667
TI  - Propranolol Attenuates Risperidone-Induced Trabecular Bone Loss in Female Mice.
AB  - Atypical antipsychotic (AA) drugs cause significant metabolic side effects, and
      clinical data are emerging that demonstrate increased fracture risk and bone loss
      after treatment with the AA, risperidone (RIS). The pharmacology underlying the
      adverse effects on bone is unknown. However, RIS action in the central nervous
      system could be responsible because the sympathetic nervous system (SNS) is known
      to uncouple bone remodeling. RIS treatment in mice significantly lowered
      trabecular bone volume fraction (bone volume/total volume), owing to increased
      osteoclast-mediated erosion and reduced osteoblast-mediated bone formation.
      Daytime energy expenditure was also increased and was temporally associated with
      the plasma concentration of RIS. Even a single dose of RIS transiently elevated
      expression of brown adipose tissue markers of SNS activity and thermogenesis,
      Pgc1a and Ucp1. Rankl, an osteoclast recruitment factor regulated by the SNS, was
      also increased 1 hour after a single dose of RIS. Thus, we inferred that bone
      loss from RIS was regulated, at least in part, by the SNS. To test this, we
      administered RIS or vehicle to mice that were also receiving the nonselective
      beta-blocker propranolol. Strikingly, RIS did not cause any changes in trabecular
      bone volume/total volume, erosion, or formation while propranolol was present.
      Furthermore, beta2-adrenergic receptor null (Adrb2(-/-)) mice were also protected
      from RIS-induced bone loss. This is the first report to demonstrate SNS-mediated
      bone loss from any AA. Because AA medications are widely prescribed, especially
      to young adults, clinical studies are needed to assess whether beta-blockers will
      prevent bone loss in this vulnerable population. 

PMID- 25853669
TI  - Computational study of a model system of enzyme-mediated [4+2] cycloaddition
      reaction.
AB  - A possible mechanistic pathway related to an enzyme-catalyzed [4+2] cycloaddition
      reaction was studied by theoretical calculations at density functional (B3LYP,
      O3LYP, M062X) and semiempirical levels (PM6-DH2, PM6) performed on a model
      system. The calculations were carried out for the key [4+2] cycloaddition step
      considering enzyme-catalyzed biosynthesis of Spinosyn A in a model reaction,
      where a reliable example of a biological Diels-Alder reaction was reported
      experimentally. In the present study it was demonstrated that the [4+2]
      cycloaddition reaction may benefit from moving along the energetically balanced
      reaction coordinate, which enabled the catalytic rate enhancement of the [4+2]
      cycloaddition pathway involving a single transition state. Modeling of such a
      system with coordination of three amino acids indicated a reliable decrease of
      activation energy by ~18.0 kcal/mol as compared to a non-catalytic
      transformation.

PMID- 25853671
TI  - Sustaining hospital financial health: A role for physician assistant leadership.

PMID- 25853670
TI  - Common and distinct impacts of autistic traits and alexithymia on social reward.
AB  - According to the social motivation hypothesis of autism, individuals with high
      levels of autistic traits experience reduced levels of reward from social
      interactions. However, empirical evidence to date has been mixed, with some
      studies reporting lower levels of social reward in individuals with Autism
      Spectrum Disorder (ASD), and others finding no difference when compared to
      typically developing controls. Alexithymia, a subclinical condition associated
      with the reduced ability to identify and describe one's own emotions, has been
      found to account for other affective difficulties observed inconsistently in
      individuals with ASD. The current study used a nonclinical sample (N = 472) to
      explore the associations between autistic traits and the value of six types of
      social reward, as measured by the Social Reward Questionnaire. In addition, we
      measured alexithymia to assess if this accounted for associations between
      autistic traits and social reward. There were three main findings. Firstly,
      higher levels of autistic traits were associated with significantly less
      enjoyment of admiration and sociability, and adding alexithymia to these models
      did not account for any additional variance. Secondly, both autistic traits and
      alexithymia were uniquely associated with reduced levels of enjoyment of
      prosocial interactions and sexual relationships. Thirdly, autistic traits were
      associated with higher levels of enjoyment of passivity and negative social
      potency, but these associations were no longer significant once alexithymia was
      taken into account, suggesting that co-occurring alexithymia accounted for these
      apparent associations. Overall, the current findings provide a novel and more
      nuanced picture of the relationship between autistic traits and social reward. 

PMID- 25853672
TI  - Handcuffs.

PMID- 25853673
TI  - Pathogenesis and management of diabetic foot ulcers.
AB  - Diabetic foot ulcers are a devastating component of diabetes progression and are
      caused by loss of glycemic control, peripheral neuropathy, peripheral vascular
      disease, and immunosuppression. An estimated 15% of patients with diabetes have
      diabetic foot ulcers. This article describes the pathogenesis, diagnosis,
      clinical management, and advances in wound treatment for diabetic foot ulcers. 

PMID- 25853674
TI  - The evolution of chronic opioid therapy and recognizing addiction.
AB  - Chronic pain is one of the most common complaints in the United States. Opioids
      have become a frequently prescribed treatment for patients with chronic
      nonmalignant pain. Concurrently, opioid use disorders have risen to epidemic
      levels. Studies investigating iatrogenic opioid addiction have been of limited
      quality. Aberrant drug-related behaviors may be warning signs of impending
      addiction. Proper screening and close monitoring are essential for managing
      patients on opioids for chronic nonmalignant pain. 

PMID- 25853675
TI  - Various chemical strategies to deceive ants in three Arhopala species
      (lepidoptera: Lycaenidae) exploiting Macaranga myrmecophytes.
AB  - Macaranga myrmecophytes (ant-plants) are generally well protected from herbivore
      attacks by their symbiotic ants (plant-ants). However, larvae of Arhopala
      (Lepidoptera: Lycaenidae) species survive and develop on specific Macaranga ant
      plant species without being attacked by the plant-ants of their host species. We
      hypothesized that Arhopala larvae chemically mimic or camouflage themselves with
      the ants on their host plant so that the larvae are accepted by the plant-ant
      species of their host. Chemical analyses of cuticular hydrocarbons showed that
      chemical congruency varied among Arhopala species; A. dajagaka matched well the
      host plant-ants, A. amphimuta did not match, and unexpectedly, A. zylda lacked
      hydrocarbons. Behaviorally, the larvae and dummies coated with cuticular
      chemicals of A. dajagaka were well attended by the plant-ants, especially by
      those of the host. A. amphimuta was often attacked by all plant-ants except for
      the host plant-ants toward the larvae, and those of A. zylda were ignored by all
      plant-ants. Our results suggested that conspicuous variations exist in the
      chemical strategies used by the myrmecophilous butterflies that allow them to
      avoid ant attack and be accepted by the plant-ant colonies. 

PMID- 25853676
TI  - Medically unexplained and explained physical symptoms in the general population:
      association with prevalent and incident mental disorders.
AB  - BACKGROUND: Clinical studies have shown that Medically Unexplained Symptoms (MUS)
      are related to common mental disorders. It is unknown how often common mental
      disorders occur in subjects who have explained physical symptoms (PHY), MUS or
      both, in the general population, what the incidence rates are, and whether there
      is a difference between PHY and MUS in this respect. AIM: To study the prevalence
      and incidence rates of mood, anxiety and substance use disorders in groups with
      PHY, MUS and combined MUS and PHY compared to a no-symptoms reference group in
      the general population. METHOD: Data were derived from the Netherlands Mental
      Health Survey and Incidence Study-2 (NEMESIS-2), a nationally representative face
      to-face survey of the general population aged 18-64 years. We selected subjects
      with explained physical symptoms only (n=1952), with MUS only (n=177), with both
      MUS and PHY (n=209), and a reference group with no physical symptoms (n=4168).
      The assessment of common mental disorders was through the Composite International
      Diagnostic Interview 3.0. Multivariate logistic regression analyses were used to
      examine the association between group membership and the prevalence and first
      incidence rates of comorbid mental disorders, adjusted for socio-demographic
      characteristics. RESULTS: MUS were associated with the highest prevalence rates
      of mood and anxiety disorders, and combined MUS and PHY with the highest
      prevalence rates of substance disorder. Combined MUS and PHY were associated with
      a higher incidence rate of mood disorder only (OR 2.9 (95%CI:1.27,6.74)).
      CONCLUSION: In the general population, PHY, MUS and the combination of both are
      related to mood and anxiety disorder, but odds are highest for combined MUS and
      PHY in relation to substance use disorder. Combined MUS and PHY are related to a
      greater incidence of mood disorder. These findings warrant further research into
      possibilities to improve recognition and early intervention in subjects with
      combined MUS and PHY.

PMID- 25853677
TI  - Different prognostic values of plasma Epstein-Barr virus DNA and maximal
      standardized uptake value of 18F-FDG PET/CT for nasopharyngeal carcinoma patients
      with recurrence.
AB  - PURPOSE: To evaluate and compare the prognostic value of Epstein-Barr virus (EBV)
      DNA and maximal standard uptake values (SUVmax ) of 18F-fluoro-2-deoxy-D-glucose
      positron emission tomography (18F-FDG-PET) in subgroups of nasopharyngeal
      carcinoma (NPC) patients with locoregional or distant recurrence. PATIENTS AND
      METHODS: A total of 194 patients with recurrent NPC (locoregional recurrence:
      107, distant recurrence: 87) were enrolled. Patients took evidence of recurrence
      performed with 18F-FDG-PET and an EBV DNA test before salvage treatment. Clinical
      parameters, the status of EBV DNA and the value of SUVmax were used for survival
      analysis using the Kaplan-Meier method and the Cox proportional hazards
      regression model. RESULTS: In the subgroup of patients with locoregional
      recurrence, patients with SUVmax<8.65 had significantly better overall survival
      (OS) (P=0.005) compared with the patients with SUVmax >=8.65. However, both
      elevated EBV DNA load (>=21,100 copies/ml) and distant SUVmax (>=13.55) were
      significantly associated with worse OS compared with the patients with EBV DNA
      <21,100 copies/ml or distant SUVmax <13.55 for the subgroup with distant
      recurrence (P=0.015 and P=0.006, respectively). The predictive ability of EBV DNA
      was superior to that of SUVmax (P=0.062). Multivariate analysis showed that
      SUVmax was only an independent prognostic factor for OS in patients with
      locoregional recurrence (P=0.042), whereas EBV DNA independently predicted OS for
      the patients with distant recurrence (P=0.007). For those patients with
      undetectable EBV DNA, SUVmax<8.65 was still an independent favorable prognostic
      factor (P=0.038). CONCLUSIONS: SUVmax is a useful biomarker for predicting OS in
      nasopharyngeal carcinoma patients with locoregional recurrence or with
      undetectable EBV DNA. Both distant SUVmax and EBV DNA appear to be independent
      predictors of OS in patients with distant recurrence; however, the predictive
      ability of EBV DNA was superior to that of SUVmax.

PMID- 25853678
TI  - Quantifying regional differences in the length of Twitter messages.
AB  - The increasing usage of social media for conversations, together with the
      availability of its data to researchers, provides an opportunity to study human
      conversations on a large scale. Twitter, which allows its users to post messages
      of up to a limit of 140 characters, is one such social media. Previous studies of
      utterances in books, movies and Twitter have shown that most of these utterances,
      when transcribed, are much shorter than 140 characters. Furthermore, the median
      length of Twitter messages was found to vary across US states. Here, we
      investigate whether the length of Twitter messages varies across different
      regions in the UK. We find that the median message length, depending on grouping,
      can differ by up to 2 characters. 

PMID- 25853679
TI  - Can persistence hunting signal male quality? A test considering digit ratio in
      endurance athletes.
AB  - Various theories have been posed to explain the fitness payoffs of hunting
      success among hunter-gatherers. 'Having' theories refer to the acquisition of
      resources, and include the direct provisioning hypothesis. In contrast, 'getting'
      theories concern the signalling of male resourcefulness and other desirable
      traits, such as athleticism and intelligence, via hunting prowess. We
      investigated the association between androgenisation and endurance running
      ability as a potential signalling mechanism, whereby running prowess, vital for
      persistence hunting, might be used as a reliable signal of male reproductive
      fitness by females. Digit ratio (2D:4D) was used as a proxy for prenatal
      androgenisation in 439 males and 103 females, while a half marathon race (21km),
      representing a distance/duration comparable with that of persistence hunting, was
      used to assess running ability. Digit ratio was significantly and positively
      correlated with half-marathon time in males (right hand: r = 0.45, p<0.001; left
      hand: r = 0.42, p<0.001) and females (right hand: r = 0.26, p<0.01; left hand: r
      = 0.23, p = 0.02). Sex-interaction analysis showed that this correlation was
      significantly stronger in males than females, suggesting that androgenisation may
      have experienced stronger selective pressure from endurance running in males. As
      digit ratio has previously been shown to predict reproductive success, our
      results are consistent with the hypothesis that endurance running ability may
      signal reproductive potential in males, through its association with prenatal
      androgen exposure. However, further work is required to establish whether and how
      females respond to this signalling for fitness. 

PMID- 25853680
TI  - A novel DNA biosensor using a ferrocenyl intercalator applied to the potential
      detection of human population biomarkers in wastewater.
AB  - A new label-free electrochemical DNA (E-DNA) biosensor using a custom synthesized
      ferrocenyl (Fc) double-stranded DNA intercalator as a redox marker is presented.
      Single-stranded DNA (ssDNA) was co-immobilized on gold electrodes with 6-mecarpto
      hexanol to control the surface density of the ssDNA probe, and hybridized with
      complementary DNA. The binding of the Fc intercalator to dsDNA was measured by
      differential pulse voltammetry. This new biosensor was optimized to allow the
      detection of single base pair mismatched sequences, able to detect as low as 10
      pM target ssDNA with a dynamic range from 10 pM to 100 nM. DNA extracted from
      wastewater was analyzed by quantitative polymerase chain reaction targeting human
      specific mitochondrial DNA (mtDNA). The aim of this approach is to enable the
      analysis of population biomarkers in wastewater for the evaluation of public
      health using wastewater-based epidemiology (WBE). The E-DNA biosensor was
      employed to detect human-specific mtDNA from wastewater before and after PCR
      amplification. The results demonstrate the feasibility of detecting human DNA
      biomarkers in wastewater using the developed biosensor, which may allow the
      further development of DNA population biomarkers for public health using WBE. 

PMID- 25853681
TI  - Risk factors for subdural haematoma in patients with spontaneous intracranial
      hypotension.
AB  - Subdural haematoma (SDH) is a potentially life-threatening complication in
      patients with spontaneous intracranial hypotension (SIH). In serious cases, SIH
      patients who present with SDHs develop neurological deficits, a decreased level
      of consciousness, or cerebral herniation, and may even require an urgent
      neurosurgical drainage. Despite numerous publications on SDHs, few report its
      potential risk factors in patients with SIH. In this study, we retrospectively
      investigated 93 consecutive SIH patients and divided them into an SDH group (n =
      25) and a non-SDH (NSDH) group (n = 68). The clinical and radiographic
      characteristics of these 93 patients were analyzed, and then univariate analysis
      and further multiple logistic regression analysis were performed to identify the
      potential risk factors for the development of SDHs. The univariate analysis
      showed that advanced age, male gender, longer clinical course, dural enhancement,
      and the venous distension sign were associated with the development of SDHs.
      However, multivariate analysis only included the latter three factors. Our study
      reveals important radiological manifestations for predicting the development of
      SDHs in patients with SIH. 

PMID- 25853682
TI  - Modular Approach to Reductive C(sp2)-H and C(sp3)-H Silylation of Carboxylic Acid
      Derivatives through Single-Pot, Sequential Transition Metal Catalysis.
AB  - We report a modular approach to catalytic reductive Csp2-H and Csp3-H silylation
      of carboxylic acid derivatives encompassing esters, ketones, and aldehydes.
      Choice of either an Ir(I)/Rh(I) or Rh(I)/Rh(I) sequence leads to either
      exhaustive reductive ester or reductive ketone/aldehyde silylation, respectively.
      Notably, a catalyst-controlled direct formation of doubly reduced silyl ethers is
      presented, specifically via Ir-catalyzed exhaustive hydrosilylation. The
      resulting silyl ethers undergo Csp2-H and benzylic Csp3-H silylation in a single
      vessel. 

PMID- 25853684
TI  - Emotions, narratives, and ethical mindfulness.
AB  - Clinical care is laden with emotions, from the perspectives of both clinicians
      and patients. It is important that emotions are addressed in health professions
      curricula to ensure that clinicians are humane healers as well as technical
      experts. Emotions have a valuable and generative role in health professional
      ethics education.The authors have previously described a narrative ethics
      pedagogy, the aim of which is to develop ethical mindfulness. Ethical mindfulness
      is a state of being that acknowledges everyday ethics and ethically important
      moments as significant in clinical care, with the aim of enabling ethical
      clinical practice. Using a sample narrative, the authors extend this concept to
      examine five features of ethical mindfulness as they relate to emotions: (1)
      being sensitized to emotions in everyday practice, (2) acknowledging and
      understanding the ways in which emotions are significant in practice, (3) being
      able to articulate the emotions at play during ethically important moments, (4)
      being reflexive and acknowledging both the generative aspects and the limitations
      of emotions, and (5) being courageous.The process of writing and engaging with
      narratives can lead to ethical mindfulness, including the capacity to understand
      and work with emotions. Strategies for productively incorporating emotions in
      narrative ethics teaching are described. This can be a challenging domain within
      medical education for both educators and health care students and thus needs to
      be addressed sensitively and responsibly. The potential benefit of educating
      health professionals in a way which addresses emotionality in an ethical
      framework makes the challenges worthwhile. 

PMID- 25853683
TI  - Pro-aggregant Tau impairs mossy fiber plasticity due to structural changes and
      Ca(++) dysregulation.
AB  - INTRODUCTION: We used an inducible mouse model expressing the Tau repeat domain
      with the pro-aggregant mutation DeltaK280 to analyze presynaptic Tau pathology in
      the hippocampus. RESULTS: Expression of pro-aggregant Tau(RDDelta) leads to
      phosphorylation, aggregation and missorting of Tau in area CA3. To test
      presynaptic pathophysiology we used electrophysiology in the mossy fiber tract.
      Synaptic transmission was severely disturbed in pro-aggregant Tau(RDDelta) and
      Tau-knockout mice. Long-term depression of the mossy fiber tract failed in pro
      aggregant Tau(RDDelta) mice. We observed an increase in bouton size, but a
      decline in numbers and presynaptic markers. Both pre-and postsynaptic structural
      deficits are preventable by inhibition of Tau(RDDelta) aggregation. Calcium
      imaging revealed progressive calcium dysregulation in boutons of pro-aggregant
      Tau(RDDelta) mice. In N2a cells we observed this even in cells without tangle
      load, whilst in primary hippocampal neurons transient Tau(RDDelta) expression
      alone caused similar Ca(++) dysregulation. Ultrastructural analysis revealed a
      severe depletion of synaptic vesicles pool in accordance with synaptic
      transmission impairments. CONCLUSIONS: We conclude that oligomer formation by
      Tau(RDDelta) causes pre- and postsynaptic structural deterioration and Ca(++)
      dysregulation which leads to synaptic plasticity deficits.

PMID- 25853685
TI  - Contemplating medicine during the Third Reich: scaffolding professional identity
      formation for medical students.
AB  - PROBLEM: The moral failures of physicians and the medical establishment in
      Germany and Austria during the Third Reich challenge medicine and medical
      education in a way few other events do. They compel medical educators to ensure
      that lessons learned from contemplating medicine during the Third Reich be
      integrated into current and future physicians' professional identities. Most
      health professions education programs, however, have not adopted this study
      domain in their curricula. APPROACH: The authors describe a new curriculum module
      "The Holocaust and Medicine"-and its implementation in October 2013 at Bar-Ilan
      University Faculty of Medicine in the Galilee, Safed, Israel, as a requirement
      for all medical students (starting with the class of 2017). This innovative
      module integrates historical facts, guided reflection, flipped classroom
      pedagogy, and program evaluation efforts. It spans 20 months of the preclinical
      curriculum, embedded within a doctoring course and a medical humanities
      longitudinal course and integrated within the clinical sciences blocks. OUTCOMES:
      The evaluation approach will seek to measure changes in learners' knowledge and
      attitudes, capture their experience with the module, and assess the module's
      contribution to their identities as future healers. NEXT STEPS: This module aims
      to sensitize learners to medicine's fundamental dilemmas (e.g., prejudice,
      assisted reproduction and suicide, physicians in war), ideally enhancing critical
      reflection on the potential danger of "slippery slopes." The authors propose that
      contemplation of medicine after the Holocaust and the implications for
      contemporary practice should be an integral component of health professions
      education to promote humanistic, ethically responsible practice.

PMID- 25853686
TI  - Comics and medicine: peering into the process of professional identity formation.
AB  - PROBLEM: Medical students experience transformative personal and professional
      changes during medical school. The medical education community has much to learn
      about how students perceive these changes, which can be dramatic and profound.
      APPROACH: Over the past six years (2009-2014), the author has taught a course on
      medical graphic narratives (or comics) to fourth-year medical students. Comics
      synergistically combine words and images to tell stories and provide an effective
      vehicle for helping students reflect on and give voice to varied experiences. In
      this course, students critically read and discuss medically themed comics and
      create their own original comic depicting a formative experience from medical
      school. OUTCOMES: To date, 58 students have taken the course, and each has
      produced an original comic. The author conducted a thematic analysis of their
      comics and identified the following themes: (1) how I found my niche, (2) the
      medical student as patient, (3) reflections on a transformative experience, (4)
      connecting with a patient, and (5) the triumphs and challenges of becoming a
      doctor. Pre/post course assessments indicate that students believe creating a
      comic can significantly improve a variety of doctoring skills and attitudes,
      including empathy, communication, clinical reasoning, writing, attention to
      nonverbal cues, and awareness of physician bias. Students' comics reveal the
      impact of formative events on their professional identity formation. NEXT STEPS:
      Medical educators should explore additional ways to effectively integrate comics
      into medical school curricula and develop robust tools for evaluating their short
      and long-term impact.

PMID- 25853687
TI  - Considering context in academic medicine: differences in demographic and
      professional characteristics and in research productivity and advancement metrics
      across seven clinical departments.
AB  - PURPOSE: To understand the disciplinary contexts in which faculty work, the
      authors examined demographics, professional characteristics, research
      productivity, and advancement across seven clinical departments at Harvard
      Medical School (HMS) and nationally. METHOD: HMS analyses included faculty from
      seven clinical departments-anesthesiology, medicine, neurology, pediatrics,
      psychiatry, radiology, and surgery-in May 2011 (N = 7,304). National analyses
      included faculty at 141 U.S. medical schools in the same seven departments as of
      December 31, 2011 (N = 91,414). The authors used chi-square and Wilcoxon Mann
      Whitney tests to compare departmental characteristics. RESULTS: Heterogeneity in
      demographics, professional characteristics, and advancement across departments
      was observed in HMS and national data. At HMS, psychiatry had the highest
      percentage of underrepresented minority faculty at 6.6% (75/1,139). In
      anesthesiology, 24.2% (128/530) of faculty were Asian, whereas in psychiatry only
      7.9% (90/1,139) were (P < .0001). Female faculty were the majority in pediatrics
      and psychiatry, whereas in surgery 26.3% (172/654) of the faculty were female (P
      < .0001). At HMS, surgery, radiology, and neurology had the shortest median times
      to promotion and the highest median number of publications, H-index, and second
      degree centrality. Neurology also had the highest percentage of faculty who had
      been principal investigators on a National Institutes of Health-funded grant.
      CONCLUSIONS: There were differences in demographics, professional
      characteristics, and advancement across clinical departments at HMS and
      nationally. The context in which faculty work, of which department is a proxy,
      should be accounted for in research on faculty career outcomes and diversity
      inclusion in academic medicine.

PMID- 25853688
TI  - Professional identity formation: creating a longitudinal framework through TIME
      (Transformation in Medical Education).
AB  - The University of Texas System established the Transformation in Medical
      Education (TIME) initiative to reconfigure and shorten medical education from
      college matriculation through medical school graduation. One of the key changes
      proposed as part of the TIME initiative was to begin emphasizing professional
      identity formation (PIF) at the premedical level. The TIME Steering Committee
      appointed an interdisciplinary task force to explore the fundamentals of PIF and
      to formulate strategies that would help students develop their professional
      identity as they transform into physicians. In this article, the authors describe
      the task force's process for defining PIF and developing a framework, which
      includes 10 key aspects, 6 domains, and 30 subdomains to characterize the
      complexity of physician identity. The task force mapped this framework onto three
      developmental phases of medical education typified by the undergraduate student,
      the clerkship-level medical student, and the graduating medical student. The task
      force provided strategies for the promotion and assessment of PIF for each
      subdomain at each of the three phases, in addition to references and resources.
      Assessments were suggested for student feedback, curriculum evaluation, and
      theoretical development. The authors emphasize the importance of longitudinal,
      formative assessment using a combination of existing assessment methods. Though
      not unique to the medical profession, PIF is critical to the practice of
      exemplary medicine and the well-being of patients and physicians. 

PMID- 25853689
TI  - The Johns Hopkins learning environment scale: measuring medical students'
      perceptions of the processes supporting professional formation.
AB  - PURPOSE: To construct a new measure to assess students' perceptions of the
      medical school learning environment (LE). METHOD: In 2012, students at Johns
      Hopkins University School of Medicine completed a survey containing 32 LE items.
      Additional questions asked about overall perception of the LE, personal growth,
      and recommending the school to a friend. Validity evidence for content, response
      process, internal structure, and relation to other variables was collected for
      interpretation of scores. RESULTS: Of 465 students surveyed, 377 (81%) completed
      all LE items. Exploratory factor analysis yielded the 28-item Johns Hopkins
      Learning Environment Scale (JHLES) with seven factors/subscales: community of
      peers, faculty relationships, academic climate, meaningful engagement, mentoring,
      inclusion and safety, and physical space. Students' overall JHLES scores ranged
      from 51 to 139, of a possible 28 to 140, with a mean (SD) of 107 (15). Overall
      scores and most subscale scores did not differ significantly by gender or
      racial/ethnic background, but did differ significantly by overall perception of
      the LE (P <= .001) and increased incrementally as overall perception improved.
      Overall JHLES scores were significantly higher for students with higher personal
      growth scores and students who would recommend the school (both P < .001).
      Subscale scores for all seven factors increased with improved overall perception
      of the LE (all P <= .005). CONCLUSIONS: The JHLES is a new measure to assess
      students' perceptions of the medical school LE, with supporting validity evidence
      and content describing the social, relational, and academic processes of medical
      school that support students' professional formation.

PMID- 25853690
TI  - A review of literature on medical students and scholarly research: experiences,
      attitudes, and outcomes.
AB  - PURPOSE: The aim of medical student research programs is to develop interest in
      and competencies related to scholarly research within future physicians. Although
      schools invest in these programs, there is currently no consensus regarding what
      benefits they confer. The goal of this review is to characterize students'
      perceptions of research programs during medical school as well as the outcomes
      attributed to these programs to provide recommendations for their optimization.
      METHOD: In June 2013, the authors reviewed the literature (1950-June 2013) and
      identified 20 reports that provided original data delineating undergraduate
      medical students' primarily self-reported experiences with, outcomes related to,
      and attitudes toward research. RESULTS: Students generally perceive their medical
      school research experiences to be positive in terms of stimulating research
      interest and developing scholarly research abilities. The majority of students
      author at least one article, and first-author publications occur more frequently
      as formal research experiences lengthen. Elective experiences do not differ from
      mandatory experiences in terms of student satisfaction or productivity. Several
      studies uncovered negative student perceptions regarding their research
      experience, including too little acknowledgment, time, and faculty interaction.
      Published studies were deficient in characterizing effects on future research
      engagement in participants. CONCLUSIONS: These findings suggest that formal
      medical student research programs can be optimized by improving the recognition
      of student effort, promoting student-mentor interaction, and allowing students
      the option to increase the duration of the research experience. Future studies
      are needed to determine whether these programs affect research participation and
      productivity later in participants' careers.

PMID- 25853691
TI  - Membrane proteome analysis of glioblastoma cell invasion.
AB  - Glioblastoma multiforme (GBM) tumor invasion is facilitated by cell migration and
      degradation of the extracellular matrix. Invadopodia are actin-rich structures
      that protrude from the plasma membrane in direct contact with the extracellular
      matrix and are proposed to participate in epithelial-mesenchymal transition. We
      characterized the invasiveness of 9 established GBM cell lines using an
      invadopodia assay and performed quantitative mass spectrometry-based proteomic
      analyses on enriched membrane fractions. All GBM cells produced invadopodia, with
      a 65% difference between the most invasive cell line (U87MG) and the least
      invasive cell line (LN229) (p = 0.0001). Overall, 1,141 proteins were identified
      in the GBM membrane proteome; the levels of 49 proteins correlated with cell
      invasiveness. Ingenuity Pathway Analysis predicted activation "cell movement" (z
      score = 2.608, p = 3.94E(-04)) in more invasive cells and generated a network of
      invasion-associated proteins with direct links to key regulators of invadopodia
      formation. Gene expression data relating to the invasion-associated proteins
      ITGA5 (integrin alpha5), CD97, and ANXA1 (annexin A1) showed prognostic
      significance in independent GBM cohorts. Fluorescence microscopy demonstrated
      ITGA5, CD97, and ANXA1 localization in invadopodia assays, and small interfering
      RNA knockdown of ITGA5 reduced invadopodia formation in U87MG cells. Thus,
      invasion-associated proteins, including ITGA5, may prove to be useful anti
      invasive targets; volociximab, a therapeutic antibody against integrin
      alpha5beta1, may be useful for treatment of patients with GBM.

PMID- 25853692
TI  - Increase in both CD14-positive and CD15-positive myeloid-derived suppressor cell
      subpopulations in the blood of patients with glioma but predominance of CD15
      positive myeloid-derived suppressor cells in glioma tissue.
AB  - Myeloid-derived suppressor cells (MDSCs), defined as CD33-positive major
      histocompatibility complex class II-negative cells, are increased in a variety of
      human tumors and are associated with immunosuppression. Myeloid-derived
      suppressor cells can be further subdivided into CD14-positive monocytic MDSC and
      CD15-positive granulocytic MDSC (polymorphonuclear MDSC) subpopulations. Here we
      analyzed MDSC subsets in the blood and tumor tissue of patients with glioma,
      including the most malignant variant, glioblastoma multiforme (GBM). CD33
      positive major histocompatibility complex class II-negative MDSCs in blood from
      21 patients with glioma and 12 healthy individuals were phenotyped and quantified
      by flow cytometry. Myeloid populations of the monocytic MDSC and
      polymorphonuclear MDSC phenotypes were both significantly increased in the blood
      of patients with GBM versus healthy controls. The myeloid activation markers CD80
      and PD-L1 could not be detected on either of these MDSC subsets; CD124, CD86, and
      CD40 were detected at similar levels on MDSCs in patients with glioma and healthy
      donors. By contrast, in tumor cell suspensions, the MDSC population consisted
      almost exclusively of CD15-positive cells. Immunohistochemistry confirmed
      infiltration of CD15-positive major histocompatibility complex class II-negative
      cells in glioma tissue samples. These data support a role for cells with an MDSC
      phenotype in the blood and tumor microenvironment of patients with GBM. 

PMID- 25853693
TI  - Neuropathologic features of suicide victims who presented with acute poststroke
      depression: significance of association with neurodegenerative disorders.
AB  - To investigate the neuropathologic characteristics of poststroke depression (PSD)
      leading to suicide, we retrospectively selected deceased subjects who had been
      diagnosed as having early PSD. Cases were divided into subjects who had committed
      suicide and those who had not. Neuropathologic examinations, including
      immunohistochemistry, were conducted. Twenty-four subjects fulfilled criteria for
      early PSD; 11 of these had committed suicide, and the other 13 had not. Lesion
      type, size of stroke, and location of stroke were variable but did not differ
      significantly between the groups. Alzheimer disease-related pathology stages also
      did not differ between the groups. Argyrophilic grain disease was found in both
      the suicide group (6 of 11) and the nonsuicide group (2 of 13); there were 2
      highly possible cases of early progressive supranuclear palsy in the suicide
      group. Together, argyrophilic grain disease and progressive supranuclear palsy
      were found significantly more frequently in suicide cases than in nonsuicide
      cases (p = 0.01). These data suggest that overlapping 4-repeat tauopathies, which
      include argyrophilic grain disease and progressive supranuclear palsy, might be
      an important aggravating factor of PSD that could lead to suicide. The presence
      of other neurodegenerative diseases does not preclude PSD because the prevalence
      of these diseases in older persons suggests that they might often occur
      concomitantly. 

PMID- 25853694
TI  - CDKN2A loss is associated with shortened overall survival in lower-grade (World
      Health Organization Grades II-III) astrocytomas.
AB  - Lower-grade (World Health Organization Grades II and III) gliomas vary widely in
      clinical behavior and are classified as astrocytic, oligodendroglial, or mixed.
      Anaplasia depends greatly on mitotic activity, with CDKN2A loss considered as the
      most common mechanism for cell cycle dysregulation. We investigated whether loss
      of the CDKN2A gene is associated with overall survival across pathologically and
      genetically defined glioma subtypes. After adjustment for IDH mutation, sex, and
      age, CDKN2A deletion was strongly associated with poorer overall survival in
      astrocytomas but not in oligodendrogliomas or oligoastrocytomas. Molecular
      classification of astrocytomas by IDH mutation, TP53 mutation, and /or ATRX loss
      of expression revealed that CDKN2A loss in IDH/TP53 mutated tumors was strongly
      associated with worse overall survival. CDKN2A loss in IDH mutated tumors with
      ATRX loss was only weakly associated with worse overall survival. These findings
      suggest that CDKN2A testing may provide further clinical aid in lower-grade
      glioma substratification beyond IDH mutation and 1p19q codeletion status,
      particularly in IDH/TP53 mutated astrocytomas. 

PMID- 25853695
TI  - Neuronal and axonal loss in normal-appearing gray matter and subpial lesions in
      multiple sclerosis.
AB  - Multiple sclerosis (MS) is a demyelinating and neurodegenerative disease of the
      CNS. Multiple sclerosis lesions include significant demyelination of the gray
      matter, which is thought to be a major contributor to both physical and cognitive
      impairment. Subpial (Type III) lesions are the most common demyelinated cortical
      lesions. We investigated neurodegenerative features of subpial lesions in
      cerebral cortex samples from 11 patients with MS and 6 nondemented non-MS
      controls. There were no significant differences in neuron and axon density
      between normally myelinated normal-appearing gray matter (NAGM) and Type III MS
      lesions. Neurons were 11.2% smaller in Type III lesions than in NAGM in the
      cingulate cortex only; Type III lesions contained 25.4% fewer NeuN-positive
      neurons compared with control cortex. Neurons in MS NAGM were 13.6% smaller than
      those in control cortex. Finally, the same regions, immunostained with anti
      SMI312 antibodies, showed reduced axon densities in Type III lesions (-31.4%) and
      NAGM (-33.0%) compared with controls. In conclusion, both NAGM and Type III
      lesions showed neurodegenerative changes, but they had no consistent differences
      in neuronal and axonal alterations. This suggests that neurodegeneration in the
      cerebral cortex of patients with MS may be independent of cortical demyelination.

PMID- 25853696
TI  - Elafin Reverses Pulmonary Hypertension via Caveolin-1-Dependent Bone
      Morphogenetic Protein Signaling.
AB  - RATIONALE: Pulmonary arterial hypertension is characterized by endothelial
      dysfunction, impaired bone morphogenetic protein receptor 2 (BMPR2) signaling,
      and increased elastase activity. Synthetic elastase inhibitors reverse
      experimental pulmonary hypertension but cause hepatotoxicity in clinical studies.
      The endogenous elastase inhibitor elafin attenuates hypoxic pulmonary
      hypertension in mice, but its potential to improve endothelial function and BMPR2
      signaling, and to reverse severe experimental pulmonary hypertension or vascular
      pathology in the human disease was unknown. OBJECTIVES: To assess elafin-mediated
      regression of pulmonary vascular pathology in rats and in lung explants from
      patients with pulmonary hypertension. To determine if elafin amplifies BMPR2
      signaling in pulmonary artery endothelial cells and to elucidate the underlying
      mechanism. METHODS: Rats with pulmonary hypertension induced by vascular
      endothelial growth factor receptor blockade and hypoxia (Sugen/hypoxia) as well
      as lung organ cultures from patients with pulmonary hypertension were used to
      assess elafin-mediated reversibility of pulmonary vascular disease. Pulmonary
      arterial endothelial cells from patients and control subjects were used to
      determine the efficacy and mechanism of elafin-mediated BMPR2 signaling.
      MEASUREMENTS AND MAIN RESULTS: In Sugen/hypoxia rats, elafin reduced elastase
      activity and reversed pulmonary hypertension, judged by regression of right
      ventricular systolic pressure and hypertrophy and pulmonary artery occlusive
      changes. Elafin improved endothelial function by increasing apelin, a BMPR2
      target. Elafin induced apoptosis in human pulmonary arterial smooth muscle cells
      and decreased neointimal lesions in lung organ culture. In normal and patient
      pulmonary artery endothelial cells, elafin promoted angiogenesis by increasing
      pSMAD-dependent and -independent BMPR2 signaling. This was linked mechanistically
      to augmented interaction of BMPR2 with caveolin-1 via elafin-mediated
      stabilization of endothelial surface caveolin-1. CONCLUSIONS: Elafin reverses
      obliterative changes in pulmonary arteries via elastase inhibition and caveolin-1
      dependent amplification of BMPR2 signaling.

PMID- 25853697
TI  - Endobronchial coils for severe emphysema are effective up to 12 months following
      treatment: medium term and cross-over results from a randomised controlled trial.
AB  - BACKGROUND: There is a clinical need for therapeutic options to reduce
      hyperinflation associated with severe emphysema. Endobronchial Coils (coils) are
      nitinol devices implanted bronchoscopically under fluoroscopic guidance to re
      tension the lung. We report the medium term effectiveness and safety of coils in
      a study of patients with emphysema. METHODS: Forty five subjects with severe
      airflow obstruction and hyperinflation received bilateral sequential treatment
      with coils (30 day interval between treatments) as part of a randomised
      controlled trial with a primary endpoint 90 days after the final treatment
      (Clinicaltrials.gov NCT01334307). Further assessments were made at 180 and 360
      days and in this study the primary outcome was the effect of coil treatment on
      the St. George's Respiratory Questionnaire (SGRQ) 360 days following treatment.
      RESULTS: At 360 days following treatment, there was an improvement in the SGRQ
      score of -6.1+/-14.0 points (p = 0.01) compared to baseline. Improvements in
      secondary outcomes were seen with increases in forced expiratory volume in the
      first second of 8.9 +/-22.2% (p = 0.002) and 6-minute walking distance of 34.1+/
      52.4m (p = 0.003). The safety profile was acceptable out to 360 days post
      treatment. CONCLUSIONS: Statistically and clinically meaningful benefits in
      quality of life, exercise capacity and pulmonary function in patients treated
      with coils are sustained twelve months after treatment. TRIAL REGISTRATION
      INFORMATION: Clinicaltrials.gov NCT01334307.

PMID- 25853698
TI  - Impact of the CFTR-potentiator ivacaftor on airway microbiota in cystic fibrosis
      patients carrying a G551D mutation.
AB  - BACKGROUND: Airway microbiota composition has been clearly correlated with many
      pulmonary diseases, and notably with cystic fibrosis (CF), an autosomal genetic
      disorder caused by mutation in the CF transmembrane conductance regulator (CFTR).
      Recently, a new molecule, ivacaftor, has been shown to re-establish the
      functionality of the G551D-mutated CFTR, allowing significant improvement in lung
      function. OBJECTIVE AND METHODS: The purpose of this study was to follow the
      evolution of the airway microbiota in CF patients treated with ivacaftor, using
      quantitative PCR and pyrosequencing of 16S rRNA amplicons, in order to identify
      quantitative and qualitative changes in bacterial communities. Three G551D
      children were followed up longitudinally over a mean period of more than one year
      covering several months before and after initiation of ivacaftor treatment.
      RESULTS: 129 operational taxonomy units (OTUs), representing 64 genera, were
      identified. There was no significant difference in total bacterial load before
      and after treatment. Comparison of global community composition found no
      significant changes in microbiota. Two OTUs, however, showed contrasting
      dynamics: after initiation of ivacaftor, the relative abundance of the anaerobe
      Porphyromonas 1 increased (p<0.01) and that of Streptococcus 1 (S. mitis group)
      decreased (p<0.05), possibly in relation to the anti-Gram-positive properties of
      ivacaftor. The anaerobe Prevotella 2 correlated positively with the pulmonary
      function test FEV-1 (r=0.73, p<0.05). The study confirmed the presumed positive
      role of anaerobes in lung function. CONCLUSION: Several airway microbiota
      components, notably anaerobes (obligate or facultative anaerobes), could be
      valuable biomarkers of lung function improvement under ivacaftor, and could shed
      light on the pathophysiology of lung disease in CF patients.

PMID- 25853701
TI  - The hypocholesterolemic and hormone modulation effects of isoflavones alone or co
      fermented with probiotic bacteria in hypercholesterolemic rats model.
AB  - This study aimed to investigate the beneficial effect of isoflavones alone or
      probiotics-co-fermented isoflavones on serum and hepatic lipid profile, serum
      steroid (SHs) and thyroid hormones (THs) of hypercholesterolemic rats (N = 48).
      Animals were fed for 8 weeks with probiotics-co-fermented isoflavones or
      isoflavones alone, beside high-fat-high-cholesterol diet. Serum was analyzed for
      cholesterols, triglycerides (TG), SHs and THs. Results demonstrated that the
      given treatments significantly decreased serum total-cholesterol (TC), low
      density-lipoprotein-cholesterol (LDL-C), high-density-lipoprotein-cholesterol
      (HDL-C), LDL/HDL ratio, and increased TG, compared to controls. The probiotics-co
      fermented isoflavones decreased TC, LDL-C and LDL/HDL ratio more effectively than
      isoflavones alone. Also, both isoflavones treatments induced a hyperthyroidism
      state, as the levels of T-T4, T-T3 and fT3 significantly increased. In addition,
      these treatments decreased testosterone and increased cortisol levels. Thus,
      isoflavones-containing-treatments, particularly probiotics-co-fermented
      isoflavones, could reduce CVD incidence by controlling lipid profile; and this
      control could in part be due to modulation of SHs and THs. 

PMID- 25853700
TI  - Caffeic acid, a phenol found in white wine, modulates endothelial nitric oxide
      production and protects from oxidative stress-associated endothelial cell injury.
AB  - INTRODUCTION: Several studies demonstrated that endothelium dependent
      vasodilatation is impaired in cardiovascular and chronic kidney diseases because
      of oxidant stress-induced nitric oxide availability reduction. The Mediterranean
      diet, which is characterized by food containing phenols, was correlated with a
      reduced incidence of cardiovascular diseases and delayed progression toward end
      stage chronic renal failure. Previous studies demonstrated that both red and
      white wine exert cardioprotective effects. In particular, wine contains Caffeic
      acid (CAF), an active component with known antioxidant activities. AIM OF THE
      STUDY: The aim of the present study was to investigate the protective effect of
      low doses of CAF on oxidative stress-induced endothelial injury. RESULTS: CAF
      increased basal as well as acetylcholine-induced NO release by a mechanism
      independent from eNOS expression and phosphorylation. In addition, low doses of
      CAF (100 nM and 1 MUM) increased proliferation and angiogenesis and inhibited
      leukocyte adhesion and endothelial cell apoptosis induced by hypoxia or by the
      uremic toxins ADMA, p-cresyl sulfate and indoxyl sulfate. The biological effects
      exerted by CAF on endothelial cells may be at least in part ascribed to
      modulation of NO release and by decreased ROS production. In an experimental
      model of kidney ischemia-reperfusion injury in mice, CAF significantly decreased
      tubular cell apoptosis, intraluminal cast deposition and leukocyte infiltration.
      CONCLUSION: The results of the present study suggest that CAF, at very low
      dosages similar to those observed after moderate white wine consumption, may
      exert a protective effect on endothelial cell function by modulating NO release
      independently from eNOS expression and phosphorylation. CAF-induced NO modulation
      may limit cardiovascular and kidney disease progression associated with oxidative
      stress-mediated endothelial injury.

PMID- 25853702
TI  - Nanostructural effects on polymer and water dynamics in cellulose biocomposites:
      (2)h and (13)c NMR relaxometry.
AB  - Improved moisture stability is desired in cellulose biocomposites. In order to
      clarify nanostructural effects, a new approach is presented where water and
      polymer matrix mobilities are characterized separately. Nanocomposites from
      cellulose nanofibers (CNF) in the xyloglucan (XG) biopolymer matrix are
      investigated at different hydration states. Films of XG, CNF, and CNF/XG
      composites are subjected to detailed (2)H and (13)C NMR relaxation studies. Since
      the (2)H NMR signal arises from heavy water and the (13)C signal from the
      polysaccharides, molecular water and polymer dynamics is for the first time
      investigated separately. In the neat components, (2)H transverse relaxation (T2)
      data are consistent with water clustering at the CNF fibril surfaces, but bulk
      spread of moisture in XG. The new method results in a description of water
      interaction with the nanoscale phases. At low hydration, water molecules at the
      CNF/XG interface exhibit higher water mobility than in neat CNF or XG, due to
      locally high water concentration. At the same time, CNF-associated interphase
      segments of XG show slower NMR-dynamics than that in neat XG. 

PMID- 25853703
TI  - External validation and calibration of IVFpredict: a national prospective cohort
      study of 130,960 in vitro fertilisation cycles.
AB  - BACKGROUND: Accurately predicting the probability of a live birth after in vitro
      fertilisation (IVF) is important for patients, healthcare providers and policy
      makers. Two prediction models (Templeton and IVFpredict) have been previously
      developed from UK data and are widely used internationally. The more recent of
      these, IVFpredict, was shown to have greater predictive power in the development
      dataset. The aim of this study was external validation of the two models and
      comparison of their predictive ability. METHODS AND FINDINGS: 130,960 IVF cycles
      undertaken in the UK in 2008-2010 were used to validate and compare the Templeton
      and IVFpredict models. Discriminatory power was calculated using the area under
      the receiver-operator curve and calibration assessed using a calibration plot and
      Hosmer-Lemeshow statistic. The scaled modified Brier score, with measures of
      reliability and resolution, were calculated to assess overall accuracy. Both
      models were compared after updating for current live birth rates to ensure that
      the average observed and predicted live birth rates were equal. The
      discriminative power of both methods was comparable: the area under the receiver
      operator curve was 0.628 (95% confidence interval (CI): 0.625-0.631) for
      IVFpredict and 0.616 (95% CI: 0.613-0.620) for the Templeton model. IVFpredict
      had markedly better calibration and higher diagnostic accuracy, with calibration
      plot intercept of 0.040 (95% CI: 0.017-0.063) and slope of 0.932 (95% CI: 0.839
      1.025) compared with 0.080 (95% CI: 0.044-0.117) and 1.419 (95% CI: 1.149-1.690)
      for the Templeton model. Both models underestimated the live birth rate, but this
      was particularly marked in the Templeton model. Updating the models to reflect
      improvements in live birth rates since the models were developed enhanced their
      performance, but IVFpredict remained superior. CONCLUSION: External validation in
      a large population cohort confirms IVFpredict has superior discrimination and
      calibration for informing patients, clinicians and healthcare policy makers of
      the probability of live birth following IVF.

PMID- 25853704
TI  - Nephropathy, but not Angiographically Proven Retinopathy, is Associated with
      Neutrophil to Lymphocyte Ratio in Patients with Type 2 Diabetes.
AB  - BACKGROUND: Type 2 Diabetes Mellitus is a leading cause of end stage renal
      disease in the worldwide. Inflammation is regarded as one of the main reasons for
      the progression of diabetes complications. We aimed to evaluate the association
      of neutrophil to lymphocyte ratio (NLR) as indicator of systemic inflammation
      with diabetic retinopathy and nephropathy. PATIENTS AND METHODS: This is a cross
      sectional study of 114 prevalent type 2 diabetic subjects. All of the patients
      underwent detailed examination for the presence of diabetic retinopathy and
      nephropathy. Diabetic retinopathy was approved and classified according to
      findings based on flouresceint fundal angiography results. Estimated glomerular
      filtration rate (eGFR) and microalbumin to creatinine ratio were calculated to
      establish the diabetic nephropathy. NLR was calculated as ratio of absolute
      neutrophil count to absolute lymphocyte count. RESULTS: Retinopathy was present
      in 55 (48.2%) out of 114 patients, whereas nephropathy was present in 62 patients
      (54.3%). NLR was significantly higher in patients with nephropathy than in
      patients without nephropathy. NLR was also positively correlated with CRP
      (p=0.017, r=0.224) and microalbuminuria (p=0.016, r=0.257) whereas negatively
      correlated with eGFR (p<0.001, r=-0.337) values in the whole cohort. NLR was
      independent predictors for diabetic nephropathy, whereas it did not appear as an
      independent associate of diabetic retinopathy. CONCLUSION: NLR and diabetic
      nephropathy have an independent association between them whereas there was no
      independent association between NLR with retinopathy in type 2 diabetic patients.

PMID- 25853705
TI  - Type 1 diabetes mellitus and exercise in competitive athletes.
AB  - AIMS: The number of patients with type 1 diabetes mellitus who are actively
      participating in competitive sports is increasing. Here, we aimed to assess
      individual experiences of competitive athletes with type 1 diabetes and to
      compare these experiences with current recommendations. METHODS: A survey of 20
      competitive athletes with type 1 diabetes, categorized as endurance (n=10) and
      non-endurance (n=10) athletes, was performed. RESULTS: Endurance and non
      endurance athletes did not differ in gender distribution, age, body mass index,
      and known diabetes duration. Self-reported target blood glucose values prior to
      exercise were lower in non-endurance than in endurance athletes (195+/-34 vs.
      137+/-28 mg/dl, P=0.001). The majority of all athletes experienced activity
      induced hypo- and hyperglycemic events, independently of exercise type. However,
      endurance athletes used additional carbohydrate units to prevent activity-induced
      hypoglycemic events more frequently without monitoring their blood glucose levels
      than non-endurance athletes (50% vs. 0%, P=0.01). The reduction of the insulin
      dose on training and competition days compared to days without exercise was
      similar for endurance and non-endurance athletes. CONCLUSION: These results point
      to a very individual adaption of the athlete's therapy during training and
      competition. However, there are distinct differences in diabetes management
      between endurance and non-endurance athletes.

PMID- 25853706
TI  - Human Islets Exhibit Electrical Activity on Microelectrode Arrays (MEA).
AB  - This study demonstrates for the first time that the microelectrode array (MEA)
      technique allows analysis of electrical activity of islets isolated from human
      biopsies. We have shown before that this method, i.e., measuring beta cell
      electrical activity with extracellular electrodes, is a powerful tool to assess
      glucose responsiveness of isolated murine islets. In the present study, human
      islets were shown to exhibit glucose-dependent oscillatory electrical activity.
      The glucose responsiveness could be furthermore demonstrated by an increase of
      insulin secretion in response to glucose. Electrical activity was increased by
      tolbutamide and inhibited by diazoxide. In human islets bursts of electrical
      activity were markedly blunted by the Na(+) channel inhibitor tetrodotoxin which
      does not affect electrical activity in mouse islets. Thus, the MEA technique
      emerges as a powerful tool to decipher online the unique features of human
      islets.Additionally, this technique will enable research with human islets even
      if only a few islets are available and it will allow a fast and easy test of
      metabolic integrity of islets destined for transplantation.

PMID- 25853707
TI  - Temporal stability of genetic variability and differentiation in the three-spined
      stickleback (Gasterosteus aculeatus).
AB  - Temporal variation in allele frequencies, whether caused by deterministic or
      stochastic forces, can inform us about interesting demographic and evolutionary
      phenomena occurring in wild populations. In spite of the continued surge of
      interest in the genetics of three-spined stickleback (Gasterosteus aculeatus)
      populations, little attention has been paid towards the temporal stability of
      allele frequency distributions, and whether there are consistent differences in
      effective size (Ne) of local populations. We investigated temporal stability of
      genetic variability and differentiation in 15 microsatellite loci within and
      among eight collection sites of varying habitat type, surveyed twice over a six
      year time period. In addition, Nes were estimated with the expectation that they
      would be lowest in isolated ponds, intermediate in larger lakes and largest in
      open marine sites. In spite of the marked differences in genetic variability and
      differentiation among the study sites, the temporal differences in allele
      frequencies, as well as measures of genetic diversity and differentiation, were
      negligible. Accordingly, the Ne estimates were temporally stable, but tended to
      be lower in ponds than in lake or marine habitats. Hence, we conclude that allele
      frequencies in putatively neutral markers in three-spined sticklebacks seem to be
      temporally stable - at least over periods of few generations - across a wide
      range of habitat types differing markedly in levels of genetic variability,
      effective population size and gene flow. 

PMID- 25853708
TI  - Comparative whole-genome analysis of clinical isolates reveals characteristic
      architecture of Mycobacterium tuberculosis pangenome.
AB  - The tubercle complex consists of closely related mycobacterium species which
      appear to be variants of a single species. Comparative genome analysis of
      different strains could provide useful clues and insights into the genetic
      diversity of the species. We integrated genome assemblies of 96 strains from
      Mycobacterium tuberculosis complex (MTBC), which included 8 Indian clinical
      isolates sequenced and assembled in this study, to understand its pangenome
      architecture. We predicted genes for all the 96 strains and clustered their
      respective CDSs into homologous gene clusters (HGCs) to reveal a hard-core, soft
      core and accessory genome component of MTBC. The hard-core (HGCs shared amongst
      100% of the strains) was comprised of 2,066 gene clusters whereas the soft-core
      (HGCs shared amongst at least 95% of the strains) comprised of 3,374 gene
      clusters. The change in the core and accessory genome components when observed as
      a function of their size revealed that MTBC has an open pangenome. We identified
      74 HGCs that were absent from reference strains H37Rv and H37Ra but were present
      in most of clinical isolates. We report PCR validation on 9 candidate genes
      depicting 7 genes completely absent from H37Rv and H37Ra whereas 2 genes shared
      partial homology with them accounting to probable insertion and deletion events.
      The pangenome approach is a promising tool for studying strain specific genetic
      differences occurring within species. We also suggest that since selecting
      appropriate target genes for typing purposes requires the expected target gene be
      present in all isolates being typed, therefore estimating the core-component of
      the species becomes a subject of prime importance. 

PMID- 25853709
TI  - The impact of antipsychotic polytherapy costs in the public health care in Sao
      Paulo, Brazil.
AB  - INTRODUCTION: Guidelines for the treatment of psychoses recommend antipsychotic
      monotherapy. However, the rate of antipsychotic polytherapy has increased over
      the last decade, reaching up to 60% in some settings. Studies evaluating the
      costs and impact of antipsychotic polytherapy in the health system are scarce.
      OBJECTIVE: To estimate the costs of antipsychotic polytherapy and its impact on
      public health costs in a sample of subjects with psychotic disorders living in
      residential facilities in the city of Sao Paulo, Brazil. METHOD: A cross
      sectional study that used a bottom-up approach for collecting costs data in a
      public health provider's perspective. Subjects with psychosis living in 20 fully
      staffed residential facilities in the city of Sao Paulo were assessed for
      clinical and psychosocial profile, severity of symptoms, quality of life, use of
      health services and pharmacological treatment. The impact of polytherapy on total
      direct costs was evaluated. RESULTS: 147 subjects were included, 134 used
      antipsychotics regularly and 38% were in use of antipsychotic polytherapy. There
      were no significant differences in clinical and psychosocial characteristics
      between polytherapy and monotherapy groups. Four variables explained 30% of
      direct costs: the number of antipsychotics, location of the residential facility,
      time living in the facility and use of olanzapine. The costs of antipsychotics
      corresponded to 94.4% of the total psychotropic costs and to 49.5% of all health
      services use when excluding accommodation costs. Olanzapine costs corresponded to
      51% of all psychotropic costs. CONCLUSION: Antipsychotic polytherapy is a huge
      economic burden to public health service, despite the lack of evidence supporting
      this practice. Great variations on antipsychotic costs explicit the need of
      establishing protocols for rational antipsychotic prescriptions and consequently
      optimising resource allocation. Cost-effectiveness studies are necessary to
      estimate the best value for money among antipsychotics, especially in low and
      middle income countries.

PMID- 25853710
TI  - Rectal application of a highly osmolar personal lubricant in a macaque model
      induces acute cytotoxicity but does not increase risk of SHIV infection.
AB  - BACKGROUND: Personal lubricant use is common during anal intercourse. Some water
      based products with high osmolality and low pH can damage genital and rectal
      tissues, and the polymer polyquaternium 15 (PQ15) can enhance HIV replication in
      vitro. This has raised concerns that lubricants with such properties may increase
      STD/HIV infection risk, although in vivo evidence is scarce. We use a macaque
      model to evaluate rectal cytotoxicity and SHIV infection risk after use of a
      highly osmolar (>8,000 mOsm/kg) water-based lubricant with pH of 4.4, and
      containing PQ15. METHODS: Cytotoxicity was documented by measuring inflammatory
      cytokines and epithelial tissue sloughing during six weeks of repeated, non
      traumatic lubricant or control buffer applications to rectum and anus. We
      measured susceptibility to SHIVSF162P3 infection by comparing virus doses needed
      for rectal infection in twenty-one macaques treated with lubricant or control
      buffer 30 minutes prior to virus exposure. RESULTS: Lubricant increased pro
      inflammatory cytokines and tissue sloughing while control buffer (phosphate
      buffered saline; PBS) did not. However, the estimated AID50 (50% animal
      infectious dose) was not different in lubricant- and control buffer-treated
      macaques (p = 0.4467; logistic regression models). CONCLUSIONS: Although the test
      lubricant caused acute cytotoxicity in rectal tissues, it did not increase
      susceptibility to infection in this macaque model. Thus neither the lubricant
      induced type/extent of inflammation nor the presence of PQ15 affected infection
      risk. This study constitutes a first step in the in vivo evaluation of lubricants
      with regards to HIV transmission.

PMID- 25853711
TI  - Snakes on the Balearic islands: an invasion tale with implications for native
      biodiversity conservation.
AB  - Biological invasions are a major conservation threat for biodiversity worldwide.
      Islands are particularly vulnerable to invasive species, especially Mediterranean
      islands which have suffered human pressure since ancient times. In the Balearic
      archipelago, reptiles represent an outstanding case with more alien than native
      species. Moreover, in the last decade a new wave of alien snakes landed in the
      main islands of the archipelago, some of which were originally snake-free. The
      identification of the origin and colonization pathways of alien species, as well
      as the prediction of their expansion, is crucial to develop effective
      conservation strategies. In this study, we used molecular markers to assess the
      allochthonous status and the putative origin of the four introduced snake species
      (Hemorrhois hippocrepis, Malpolon monspessulanus, Macroprotodon mauritanicus and
      Rhinechis scalaris) as well as ecological niche models to infer their patterns of
      invasion and expansion based on current and future habitat suitability. For most
      species, DNA sequence data suggested the Iberian Peninsula as the potential
      origin of the allochthonous populations, although the shallow phylogeographic
      structure of these species prevented the identification of a restricted source
      area. For all of them, the ecological niche models showed a current low habitat
      suitability in the Balearic, which is however predicted to increase significantly
      in the next few decades under climate change scenarios. Evidence from direct
      observations and spatial distribution of the first-occurrence records of alien
      snakes (but also lizards and worm lizards) suggest the nursery trade, and in
      particular olive tree importation from Iberian Peninsula, as the main pathway of
      introduction of alien reptiles in the Balearic islands. This trend has been
      reported also for recent invasions in NE Spain, thus showing that olive trees
      transplantation may be an effective vector for bioinvasion across the
      Mediterranean. The combination of molecular and ecological tools used in this
      study reveals a promising approach for the understanding of the complex invasion
      process, hence guiding conservation management actions. 

PMID- 25853712
TI  - Charcoal reflectance reveals early holocene boreal deciduous forests burned at
      high intensities.
AB  - Wildfire size, frequency, and severity are increasing in the Alaskan boreal
      forest in response to climate warming. One of the potential impacts of this
      changing fire regime is the alteration of successional trajectories, from black
      spruce to mixed stands dominated by aspen, a vegetation composition not
      experienced since the early Holocene. Such changes in vegetation composition may
      consequently alter the intensity of fires, influencing fire feedbacks to the
      ecosystem. Paleorecords document past wildfire-vegetation dynamics and as such,
      are imperative for our understanding of how these ecosystems will respond to
      future climate warming. For the first time, we have used reflectance measurements
      of macroscopic charcoal particles (>180MUm) from an Alaskan lake-sediment record
      to estimate ancient charring temperatures (termed pyrolysis intensity). We
      demonstrate that pyrolysis intensity increased markedly from an interval of birch
      tundra 11 ky ago (mean 1.52%Ro; 485 degrees C), to the expansion of trees on the
      landscape ~10.5 ky ago, remaining high to the present (mean 3.54%Ro; 640 degrees
      C) irrespective of stand composition. Despite differing flammabilities and
      adaptations to fire, the highest pyrolysis intensities derive from two intervals
      with distinct vegetation compositions. 1) the expansion of mixed aspen and spruce
      woodland at 10 cal. kyr BP, and 2) the establishment of black spruce, and the
      modern boreal forest at 4 cal. kyr BP. Based on our analysis, we infer that
      predicted expansion of deciduous trees into the boreal forest in the future could
      lead to high intensity, but low severity fires, potentially moderating future
      climate-fire feedbacks.

PMID- 25853713
TI  - Interstitial fluid colloid osmotic pressure in healthy children.
AB  - OBJECTIVE: The colloid osmotic pressure (COP) of plasma and interstitial fluid
      play important roles in transvascular fluid exchange. COP values for monitoring
      fluid balance in healthy and sick children have not been established. This study
      set out to determine reference values of COP in healthy children. MATERIALS AND
      METHODS: COP in plasma and interstitial fluid harvested from nylon wicks was
      measured in 99 healthy children from 2 to 10 years of age. Nylon wicks were
      implanted subcutaneously in arm and leg while patients were sedated and intubated
      during a minor surgical procedure. COP was analyzed in a colloid osmometer
      designed for small fluid samples. RESULTS: The mean plasma COP in all children
      was 25.6 +/- 3.3 mmHg. Arbitrary division of children in four different age
      groups, showed no significant difference in plasma or interstitial fluid COP
      values for patients less than 8 years, whereas patients of 8-10 years had
      significant higher COP both in plasma and interstitial fluid. There were no
      gender difference or correlation between COP in interstitial fluid sampled from
      arm and leg and no significant effect on interstitial COP of gravity. Prolonged
      implantation time did not affect interstitial COP. CONCLUSION: Plasma and
      interstitial COP in healthy children are comparable to adults and COP seems to
      increase with age in children. Knowledge of the interaction between colloid
      osmotic forces can be helpful in diseases associated with fluid imbalance and may
      be crucial in deciding different fluid treatment options. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT01044641.

PMID- 25853714
TI  - De novo RNA-Seq analysis of the venus clam, Cyclina sinensis, and the
      identification of immune-related genes.
AB  - The Venus clam, Cyclina sinensis, is one of the most important bivalves in China.
      In recent years, increasing expansive morbidity has occurred in breeding areas,
      imposing significant losses on the national economy. To understand the molecular
      mechanisms of immune-related genes, we analyzed and sequenced hemolymph samples
      that were injected with two pathogenic microorganisms using the Illumina Miseq
      system. After trimming, more than 12 M PE reads with an average length greater
      than 410 bp were assembled into 70,079 transcripts with a mean length of 980 bp.
      Using a homology analysis, 102 (135 transcripts) potentially immune-related genes
      were identified, and most of them exhibited a similar pattern in both samples.
      These data indicated that the response of the clam to both types of bacterial
      infection might follow a similar molecular mechanism. Using the TreeFam method,
      9,904 gene families and 1,031 unique families of the clam were preliminarily
      classified in comparison to five related species. A significant number of SSRs
      were identified, which could facilitate the identification of polymorphisms in
      Venus clam populations. These datasets will improve our knowledge of the
      molecular mechanisms driving the immune response to bacterial infection in clam
      populations and will provide basic data about clam breeding and disease control. 

PMID- 25853716
TI  - Peer effects in unethical behavior: standing or reputation?
AB  - Recent empirical evidence shows that working in an unsupervised, isolated
      situation under competition, can increase dishonest behavior to achieve prestige.
      However, could working in a common space, in the presence of colleagues affect
      cheating? Here, we examine how familiar-peer influence, supervision and social
      incentives affect worker performance and dishonest behavior. First, we show that
      working in the presence of peers is an effective mechanism to constrain
      honest/dishonest behavior compared to an isolated work situation (experiment 1).
      Second, we demonstrate that the mere suspicion of dishonesty from another peer is
      not enough to affect individual cheating behavior (experiment 2), suggesting that
      reputation holds great importance in a worker's self-image acting as a strong
      social incentives. Third, we show that when the suspicion of dishonesty increases
      with multiple peers behaving dishonestly, the desire to increase standing is
      sufficient to nudge individuals' behavior back to cheating at the same levels as
      isolated situations (experiment 3). 

PMID- 25853717
TI  - Multidimensional determinants of family caregiver burden in Alzheimer's disease.
AB  - BACKGROUND: Caregiver burden is a complex and multidimensional construct.
      Although previous studies have explored numerous factors associated with
      caregiver burden, these factors have not been identified with a large population
      based sample in a theory-based multidimensional way. This study explores
      multidimensional determinants associated with family caregiver burden to
      determine the main contributors of caregiver burden in Alzheimer's disease (AD)
      using a large community dataset. METHODS: A retrospective secondary data analysis
      was conducted on 1,133 patients with AD and 1,133 primary caregivers who were
      registered in a metropolitan city dementia center in South Korea. The patient
      data included socio-demographic and disease profiles. The caregiver data
      consisted of socio-demographic and caregiving profiles. RESULTS: The study
      results identified that dementia-related factors were the most significant
      factors, representing 25.6% of caregiver burden and were followed by caregiving
      related factors explaining caregiver burden significantly. Behavioral problems
      and instrumental activities of daily living (IADL) dependency of the patient,
      spousal relationship, hours of caregiving, and the number of diseases associated
      with the caregiver were found to be significant individual variables.
      CONCLUSIONS: It is vital to develop a service and support program with a greater
      emphasis on the behavioral problems and IADL deficiency of patients with AD as
      well as on improving the competence ability of caregivers to deal with such
      difficulties.

PMID- 25853718
TI  - How Parents' Lack of Awareness Could Be Associated With Foreign Body Aspiration
      in Children.
AB  - Foreign body aspiration (FBA) in preschool children is a worldwide challenging
      clinical problem that can result in life-threatening complications. Three cases
      of FBA in preschool children are presented. All the children were admitted to the
      hospital with asthma-like symptoms, without any aspiration history. Although FBA
      was considered in differential diagnosis, there was no strong evidence to support
      this diagnosis. The persistence of symptoms despite the appropriate treatment for
      the asthma symptoms was the main reason for the reconsideration of FBA. All of
      the children underwent bronchoscopy, with the successful removal of small organic
      food items from the main bronchi. The main cause of FBA was the parents' lack of
      awareness concerning the risk of FBA when small organic food items are provided
      to preschool children. These cases demonstrate that some parents are unfamiliar
      with the risk of FBA when small organic food items are provided to their
      children. It is crucial to make it understood that consideration of FBA should be
      maintained throughout the clinical course of patients with an acute onset of
      respiratory symptoms, despite the initial lack of evidence to support this
      diagnosis, and that parental education about the causes and hazards of this
      condition may be the best preventive measure to decrease its incidence. 

PMID- 25853719
TI  - Fainting Starting Parenteral Nutrition.
AB  - Complications such as mechanical accidents, infections, and thrombosis are
      commonly described in the presence of a central venous catheter. We present a
      case of a boy who had fainting episodes due to dislocation of a central venous
      catheter. 

PMID- 25853720
TI  - Extraocular cranial nerve palsies in children.
AB  - Visual disturbances resulting from acute nerve paralysis of the muscles
      controlling eye movements can be challenging to evaluate in the pediatric
      population. Children may not be capable of describing symptoms or providing an
      adequate history. Therefore, it is important to have an understanding of the
      anatomical course of the extraocular cranial nerves and clinical manifestations
      of their dysfunction. We report 2 cases of extraocular cranial nerve palsies and,
      in addition to an anatomical review, discuss the common etiologies of paralysis
      and the importance of ophthalmological and neurological follow-up to ensure
      optimal long-term visual function. 

PMID- 25853721
TI  - Where Is the Air Coming From? A Case Report of an Adolescent With Cervicofacial
      Emphysema.
AB  - Cervicofacial subcutaneous emphysema is uncommon in children and adolescents.
      When it occurs, it is often a result of trauma, surgery, or complication of
      pneumomediastinum. We report a case of an adolescent with isolated cervicofacial
      emphysema likely from an ulcer in his buccal mucosa. 

PMID- 25853722
TI  - Status Epilepticus Due to Cat Scratch Disease: Recognition, Diagnosis, and
      Thoughts on Pathogenesis.
AB  - Despite the publication of a number of case reports since the 1950s, physician
      awareness of the unique relationship between cat scratch disease (CSD) and acute
      encephalopathy remains limited. This report alerts emergency medicine physicians
      to include CSD encephalopathy (CSDE) in the differential diagnosis when a
      previously healthy child presents with status epilepticus. Prompt recognition of
      this relationship impacts the selection of initial diagnostic studies and
      antibiotic choices and permits reliable insight into prognosis. The 2 cases are
      from different eras and demonstrate the significant diagnostic advances in the
      past 3 decades for Bartonella henselae infection. Both children were treated with
      antibiotics, and both had resolution of all neurological symptoms. However, the
      role of antibiotics in the treatment and outcome of CSDE remains speculative.
      Lastly, the report suggests potential areas of investigation to address immune
      mediated mechanisms in the pathogenesis of CSDE.

PMID- 25853723
TI  - Cephalic Tetanus in an Immunized Teenager: An Unusual Case Report.
AB  - Tetanus is a rare disease in developed countries but is prevalent worldwide. It
      has significant morbidity and mortality. The causative agent Clostridium tetani
      is ubiquitous in nature. In the United States, approximately 50 to 100 cases are
      reported per year but rarely in immunocompetent, fully immunized patients. Of the
      four types of tetanus (generalized, neonatal, cephalic, and localized), cephalic
      is the least common. We present a case of cephalic tetanus in a 14-year-old boy
      who completed his primary immunizations with a video of his physical examination
      findings. 

PMID- 25853724
TI  - Three-dimensional surface-enhanced Raman scattering hotspots in spherical
      colloidal superstructure for identification and detection of drugs in human
      urine.
AB  - Rapid component separation and robust surface-enhanced Raman scattering (SERS)
      identification of drugs in real human urine remain an attractive challenge
      because of the sample complexity, low molecular affinity for metal surface, and
      inefficient use of hotspots in one- or two-dimensional (2D) geometries. Here, we
      developed a 5 min strategy of cyclohexane (CYH) extraction for separating
      amphetamines from human urine. Simultaneously, an oil-in-water emulsion method is
      used to assemble monodisperse Ag nanoparticles in the CYH phase into spherical
      colloidal superstructures in the aqueous phase. These superstructures create
      three-dimensional (3D) SERS hotspots which exist between every two adjacent
      particles in 3D space, break the traditional 2D limitation, and extend the
      hotspots into the third dimension along the z-axis. In this platform, a
      conservative estimate of Raman enhancement factor is larger than 10(7), and the
      same CYH extraction processing results in a high acceptability and enrichment of
      drug molecules in 3D hotspots which demonstrates excellent stability and
      reproducibility and is suitable for the quantitative examination of amphetamines
      in both aqueous and organic phases. Parallel ultraperformance liquid
      chromatography (UPLC) examinations corroborate an excellent performance of our
      SERS platform for the quantitative analysis of methamphetamine (MA) in both
      aqueous solution and real human urine, of which the detection limits reach 1 and
      10 ppb, respectively, with tolerable signal-to-noise ratios. Moreover, SERS
      examinations on different proportions of MA and 3,4-methylenedioxymethamphetamine
      (MDMA) in human urine demonstrate an excellent capability of multiplex
      quantification of ultratrace analytes. By virtue of a spectral classification
      algorithm, we realize the rapid and accurate recognition of weak Raman signals of
      amphetamines at trace levels and also clearly distinguish various proportions of
      multiplex components. Our platform for detecting drugs promises to be a great
      prospect for a rapid, reliable, and on-spot analyzer. 

PMID- 25853725
TI  - Opioid use in the management of diabetic peripheral neuropathy (DPN) in a large
      commercially insured population.
AB  - OBJECTIVE: To examine the proportion of diabetic peripheral neuropathy (DPN)
      patients receiving pharmacologic DPN treatments and specifically to identify the
      rates and factors associated with opioid use and first-line opioid use. METHODS:
      A 10% sample of IMS-LifeLink claims data from 1998 through 2008 was used. The
      study population consisted of diabetic patients who met DPN criteria using a
      validated DPN algorithm. Multivariable logistic regression controlling for
      demographics, comorbidities, and other clinical characteristics was used to
      identify factors associated with any DPN pharmacologic treatment, any opioid use,
      and first-line opioid treatment. Sensitivity analyses were conducted to explore
      variations in exclusion criteria as well as opioid use definitions. RESULTS: A
      total of 666 DPN patients met inclusion criteria and pharmacologic treatment was
      received by 288 patients (43.24%) and of those, 154 (53.47%) had DPN-related
      opioid use and 96 (33.33%) received opioid as first-line treatment. Persons with
      diabetic complications were more likely to use opioids (odds ratio=4.53; 95%
      confidence interval, 1.09-18.92). Food and Drug Administration-approved DPN
      agents duloxetine 1.04% (n=3) and pregabalin 5.56% (n=16) had much lower rates of
      use. DPN-related drug use and DPN-related opioid usage increased as we used less
      restrictive samples in sensitivity analyses. CONCLUSIONS: Opioids were the most
      frequently prescribed first-line agents for DPN. More than 50% of DPN patients
      remained untreated with pharmacologic agents 1 year after a DPN diagnosis.

PMID- 25853727
TI  - Correction: The pH-responsive PacC transcription factor of Aspergillus fumigatus
      governs epithelial entry and tissue invasion during pulmonary aspergillosis.
AB  - [This corrects the article DOI: 10.1371/journal.ppat.1004413.].

PMID- 25853726
TI  - Phosphorylation of mutationally introduced tyrosine in the activation loop of
      HER2 confers gain-of-function activity.
AB  - Amplification, overexpression, and somatic mutation of the HER2 gene have been
      reported to play a critical role in tumorigenesis of various cancers. The HER2
      H878Y mutation was recently reported in 11% of hepatocellular carcinoma (HCC)
      patients. However, its functional impact on the HER2 protein and its role in
      tumorigenesis has not been determined. Here, we show that HER2 H878Y is a gain-of
      function mutation. Y878 represents a phosphorylation site, and phospho-Y878
      interacts with R898 residue to stabilize the active conformation of HER2, thereby
      enhancing its kinase activity. H878Y mutant is transforming and the transformed
      cells are sensitive to HER2 kinase inhibitors. Thus, our study reveals the
      following novel mechanism underlying the tumorigenic function of the HER2 H878Y
      mutation: the introduction of a tyrosine residue into the kinase activation loop
      via mutagenesis modulates the conformation of the kinase, thereby enhancing its
      activity. 

PMID- 25853728
TI  - Effect of resource spatial correlation and hunter-fisher-gatherer mobility on
      social cooperation in Tierra del Fuego.
AB  - This article presents an agent-based model designed to explore the development of
      cooperation in hunter-fisher-gatherer societies that face a dilemma of sharing an
      unpredictable resource that is randomly distributed in space. The model is a
      stylised abstraction of the Yamana society, which inhabited the channels and
      islands of the southernmost part of Tierra del Fuego (Argentina-Chile). According
      to ethnographic sources, the Yamana developed cooperative behaviour supported by
      an indirect reciprocity mechanism: whenever someone found an extraordinary
      confluence of resources, such as a beached whale, they would use smoke signals to
      announce their find, bringing people together to share food and exchange
      different types of social capital. The model provides insight on how the spatial
      concentration of beachings and agents' movements in the space can influence
      cooperation. We conclude that the emergence of informal and dynamic communities
      that operate as a vigilance network preserves cooperation and makes defection
      very costly. 

PMID- 25853730
TI  - Correction to "Catalytic Mechanism of Hyaluronate Lyase from Streptococcus
      pneumoniae: Quantum Mechanical/Molecular Mechanical and Density Functional Theory
      Studies".

PMID- 25853731
TI  - Biopatterning of Silk Proteins for Soft Micro-optics.
AB  - Silk proteins from spiders and silkworms have been proposed as outstanding
      candidates for soft micro-optic and photonic applications because of their
      optical transparency, unique biological properties, and mechanical robustness.
      Here, we present a method to form microstructures of the two constituent silk
      proteins, fibroin and sericin for use as an optical biomaterial. Using
      photolithography, chemically modified silk protein photoresists are patterned in
      2D arrays of periodic patterns and Fresnel zone plates. Angle-dependent
      iridescent colors are produced in these periodic micropatterns because of the
      Bragg diffraction. Silk protein photolithography can used to form patterns on
      different substrates including flexible sheets with features of any shape with
      high fidelity and resolution over large areas. Finally, we show that these
      mechanically stable and transparent iridescent architectures are also completely
      biodegradable. This versatile and scalable technique can therefore be used to
      develop biocompatible, soft micro-optic devices that can be degraded in a
      controlled manner. 

PMID- 25853729
TI  - Time, monetary and other costs of participation in family-based child weight
      management interventions: qualitative and systematic review evidence.
AB  - BACKGROUND: Childhood overweight and obesity have health and economic impacts on
      individuals and the wider society. Families participating in weight management
      programmes may foresee or experience monetary and other costs which deter them
      from signing up to or completing programmes. This is recognised in the health
      economics literature, though within this sparse body of work, costs to families
      are often narrowly defined and not fully accounted for. A societal perspective
      incorporating a broader array of costs may provide a more accurate picture. This
      paper brings together a review of the health economics literature on the costs to
      families attending child weight management programmes with qualitative data from
      families participating in a programme to manage child overweight and obesity.
      METHODS: A search identified economic evaluation studies of lifestyle
      interventions in childhood obesity. The qualitative work drew on interviews with
      families who attended a weight management intervention in three UK regions.
      RESULTS: We identified four cost-effectiveness analyses that include information
      on costs to families. These were categorised as direct (e.g. monetary) and
      indirect (e.g. time) costs. Our analysis of qualitative data demonstrated that,
      for families who attended the programme, costs were associated both with
      participation on the scheme and with maintaining a healthy lifestyle afterwards.
      Respondents reported three kinds of cost: time-related, social/emotional and
      monetary. CONCLUSION: Societal approaches to measuring cost-effectiveness provide
      a framework for assessing the monetary and non-monetary costs borne by
      participants attending treatment programmes. From this perspective, all costs
      should be considered in any analysis of cost-effectiveness. Our data suggest that
      family costs are important, and may act as a barrier to the uptake, completion
      and maintenance of behaviours to reduce child obesity. These findings have
      implications for the development and implementation of child weight initiatives
      in particular, in relation to reducing inequalities in health.

PMID- 25853732
TI  - Small RNA in the acid tolerance response of Salmonella and their role in
      virulence.

PMID- 25853733
TI  - Comparative virulence of urinary and bloodstream isolates of extra-intestinal
      pathogenic Escherichia coli in a Galleria mellonella model.
AB  - Extra-intestinal pathogenic Escherichia coli (ExPEC) are a significant cause of
      urinary tract infections and bacteraemia worldwide. Currently no single virulence
      factor or ExPEC lineage has been identified as the sole contributor to severe
      extra-intestinal infection and/or urosepsis. Galleria mellonella has recently
      been established as a simple model for studying the comparative virulence of
      ExPEC. In this study we investigated the virulence of 40 well-characterized ExPEC
      strains, in G. mellonella, by measuring mortality (larvae survival), immune
      recognition/response (melanin production) and cell damage (lactate dehydrogenase
      production). Although mortality was similar between urinary and bloodstream
      isolates, it was heightened for community-associated infections, complicated UTIs
      and urinary-source bacteraemia. Isolates of ST131 and those possessing afa/dra,
      ompT and serogroup O6 were also associated with heightened virulence. 

PMID- 25853734
TI  - Peptides for specifically targeting nanoparticles to cellular organelles: quo
      vadis?
AB  - The interfacing of nanomaterials and especially nanoparticles within all aspects
      of biological research continues to grow at a nearly unabated pace with projected
      applications focusing on powerful new tools for cellular labeling, imaging, and
      sensing, theranostic materials, and drug delivery. At the most fundamental level,
      many of these nanoparticles are meant to target not only very specific cell
      types, regardless of whether they are in a culture, tissue, an animal model, or
      ultimately a patient, but also in many cases a specific subcellular organelle.
      During this process, these materials will undergo a complex journey that must
      first find the target cell of interest, then be taken up by those cells across
      the extracellular membrane, and ultimately localize to a desired subcellular
      organelle, which may include the nucleus, plasma membrane, endolysosomal system,
      mitochondria, cytosol, or endoplasmic reticulum. To accomplish these complex
      tasks in the correct sequence, researchers are increasingly interested in
      selecting for and exploiting targeting peptides that can impart the requisite
      capabilities to a given nanoparticle construct. There are also a number of
      related criteria that need careful consideration for this undertaking centering
      on the nature and properties of the peptide vector itself, the peptide
      nanoparticle conjugate characteristics, and the target cell. Here, we highlight
      some important issues and key research areas related to this burgeoning field. We
      begin by providing a brief overview of some criteria for optimal attachment of
      peptides to nanoparticles, the predominant methods by which nanoparticles enter
      cells, and some of the peptide sequences that have been utilized to facilitate
      nanoparticle delivery to cells focusing on those that engender the initial
      targeting and uptake. Because almost all materials delivered to cells by peptides
      utilize the endosomal system of vesicular transport and in many cases remain
      sequestered within the vesicles, we critically evaluate the issue of endosomal
      escape in the context of some recently reported successes in this regard.
      Following from this, peptides that have been reported to deliver nanoparticles to
      specific subcellular compartments are examined with a focus on what they
      delivered and the putative mechanisms by which they were able to accomplish this.
      The last section focuses on two areas that are critical to realizing this overall
      approach in the long term. The first is how to select for peptidyl sequences
      capable of improved or more specific cellular or subcellular targeting based upon
      principles commonly associated with drug discovery. The second looks at what has
      been done to create modular peptides that incorporate multiple desirable
      functionalities within a single, contiguous sequence. This provides a viable
      alternative to either the almost insurmountable challenge of finding one sequence
      capable of all functions or, alternatively, attaching different peptides with
      different functionalities to the same nanoparticle in different ratios when
      trying to orchestrate their net effects. Finally, we conclude with a brief
      perspective on the future evolution and broader impact of this growing area of
      bionanoscience. 

PMID- 25853736
TI  - Comparison of Two Available RNA Extraction Protocols for microRNA Amplification
      in Serum Samples.
AB  - BACKGROUND: microRNAs play a critical role in many biological processes such as
      cell proliferation and maturation, apoptosis, regulation of chronic inflammation
      and development of cancer. METHODS: In this study is described a protocol for the
      isolation of RNA from serum and subsequent determination of miRNA expression
      levels using TaqMan-based MGB Real-Time PCR detection. RNA was extracted using
      two different isolation methods including available kits RNAzol and a modified
      RNAzol protocol. In all cases, RNA was eluted in RNase free H2 O, kept frozen
      until analysis and the presence of contaminants assessed by NanoDrop
      spectrophotometry. RESULTS: Higher RNA quantity was observed in RNAzol (378.8
      ng/MUl) vs RNAzol modified protocol (226.5 ng/MUl) and a better performance in
      terms of RNA extraction yield and purity. Subsequently, measurements of
      endogenous miRNAs (RNU43), cellular miRNAs (mir155 and mir146a) and EBV miRNAs
      (mirBART2-5p, mirBART15 and mirBART22) were performed by RT-qPCR. CONCLUSION: In
      contrast to the findings in terms of purity and quantity, the amplifiable RNA was
      more abundant using RNAzol modified protocol compared to not modified protocol.

PMID- 25853735
TI  - Advanced echocardiography in adult zebrafish reveals delayed recovery of heart
      function after myocardial cryoinjury.
AB  - Translucent zebrafish larvae represent an established model to analyze genetics
      of cardiac development and human cardiac disease. More recently adult zebrafish
      are utilized to evaluate mechanisms of cardiac regeneration and by benefiting
      from recent genome editing technologies, including TALEN and CRISPR, adult
      zebrafish are emerging as a valuable in vivo model to evaluate novel disease
      genes and specifically validate disease causing mutations and their underlying
      pathomechanisms. However, methods to sensitively and non-invasively assess
      cardiac morphology and performance in adult zebrafish are still limited. We here
      present a standardized examination protocol to broadly assess cardiac performance
      in adult zebrafish by advancing conventional echocardiography with modern speckle
      tracking analyses. This allows accurate detection of changes in cardiac
      performance and further enables highly sensitive assessment of regional
      myocardial motion and deformation in high spatio-temporal resolution. Combining
      conventional echocardiography measurements with radial and longitudinal velocity,
      displacement, strain, strain rate and myocardial wall delay rates after
      myocardial cryoinjury permitted to non-invasively determine injury dimensions and
      to longitudinally follow functional recovery during cardiac regeneration. We show
      that functional recovery of cryoinjured hearts occurs in three distinct phases.
      Importantly, the regeneration process after cryoinjury extends far beyond the
      proposed 45 days described for ventricular resection with reconstitution of
      myocardial performance up to 180 days post-injury (dpi). The imaging modalities
      evaluated here allow sensitive cardiac phenotyping and contribute to further
      establish adult zebrafish as valuable cardiac disease model beyond the larval
      developmental stage. 

PMID- 25853737
TI  - Disputing Lamarckian epigenetic inheritance in mammals.
AB  - A recent study finds that changes to transcription and DNA methylation resulting
      from in utero exposure to environmental endocrine-disrupting chemicals are not
      inherited across generations. 

PMID- 25853738
TI  - Lancet dynamics in greater horseshoe bats, Rhinolophus ferrumequinum.
AB  - Echolocating greater horseshoe bats (Rhinolophus ferrumequinum) emit their
      biosonar pulses nasally, through nostrils surrounded by fleshy appendages
      ('noseleaves') that diffract the outgoing ultrasonic waves. Movements of one
      noseleaf part, the lancet, were measured in live bats using two synchronized high
      speed video cameras with 3D stereo reconstruction, and synchronized with pulse
      emissions recorded by an ultrasonic microphone. During individual broadcasts, the
      lancet briefly flicks forward (flexion) and is then restored to its original
      position. This forward motion lasts tens of milliseconds and increases the
      curvature of the affected noseleaf surfaces. Approximately 90% of the maximum
      displacements occurred within the duration of individual pulses, with 70%
      occurring towards the end. Similar lancet motions were not observed between
      individual pulses in a sequence of broadcasts. Velocities of the lancet motion
      were too small to induce Doppler shifts of a biologically-meaningful magnitude,
      but the maximum displacements were significant in comparison with the overall
      size of the lancet and the ultrasonic wavelengths. Three finite element models
      were made from micro-CT scans of the noseleaf post mortem to investigate the
      acoustic effects of lancet displacement. The broadcast beam shapes were found to
      be altered substantially by the observed small lancet movements. These findings
      demonstrate that-in addition to the previously described motions of the anterior
      leaf and the pinna-horseshoe bat biosonar has a third degree of freedom for fast
      changes that can happen on the time scale of the emitted pulses or the returning
      echoes and could provide a dynamic mechanism for the encoding of sensory
      information. 

PMID- 25853739
TI  - Expanding the forefront of strong organic Bronsted acids: proton-catalyzed
      hydroamination of unactivated alkenes and activation of Au(I) for alkyne
      hydroamination.
AB  - The synthesis of a solid, bench-stable, strong organic Bronsted acid with a
      computed pKa of 0.9 is reported. An X-ray crystal structure and DFT calculations
      are provided which offer insight into the bonding of this acid. The application
      of this strong organic Bronsted acid as a catalyst for the intermolecular
      hydroamination of unactivated alkenes and as an activator for Au(I)-catalyzed
      alkyne hydroamination with anilines is described. 

PMID- 25853740
TI  - Probing the Limits of Conventional Extended X-ray Absorption Fine Structure
      Analysis Using Thiolated Gold Nanoparticles.
AB  - We present a method for quantifying the accuracy of extended X-ray absorption
      fine structure (EXAFS) fitting models. As a test system, we consider the
      structure of bare Au147 nanoparticles as well as particles bound with thiol
      ligands, which are used to systematically vary disorder in the atomic structure
      of the nanoparticles. The accuracy of the fitting model is determined by
      comparing two distributions of bond lengths: (1) a direct average over a
      molecular dynamics (MD) trajectory using forces and energies from density
      functional theory (DFT) and (2) a fit to the theoretical EXAFS spectra generated
      from that same trajectory. Both harmonic and quasi-harmonic EXAFS fitting models
      are used to characterize the first-shell Au-Au bond length distribution. The
      harmonic model is found to significantly underestimate the coordination number,
      disorder, and bond length. The quasi-harmonic model, which includes the third
      cumulant of the first-shell bond length distribution, yields accurate bond
      lengths, but incorrectly predicts a decrease in particle size and little change
      in the disorder with increasing thiol ligands. A direct analysis of the MD data
      shows that the particle surfaces become much more disordered with ligand binding,
      and the high disorder is incorrectly interpreted by the EXAFS fitting models. Our
      DFT calculations compare well with experimental EXAFS measurements of Au
      nanoparticles, synthesized using a dendrimer encapsulation technique, showing
      that systematic errors in EXAFS fitting models apply to nanoparticles 1-2 nm in
      size. Finally we show that a combination of experimental EXAFS analysis with
      candidate models from DFT is a promising strategy for a more accurate
      determination of nanoparticle structures. 

PMID- 25853741
TI  - The next epidemic--lessons from Ebola.

PMID- 25853742
TI  - Medicare's step back from global payments--unbundling postoperative care.

PMID- 25853743
TI  - Randomized trial of primary PCI with or without routine manual thrombectomy.
AB  - BACKGROUND: During primary percutaneous coronary intervention (PCI), manual
      thrombectomy may reduce distal embolization and thus improve microvascular
      perfusion. Small trials have suggested that thrombectomy improves surrogate and
      clinical outcomes, but a larger trial has reported conflicting results. METHODS:
      We randomly assigned 10,732 patients with ST-segment elevation myocardial
      infarction (STEMI) undergoing primary PCI to a strategy of routine upfront manual
      thrombectomy versus PCI alone. The primary outcome was a composite of death from
      cardiovascular causes, recurrent myocardial infarction, cardiogenic shock, or New
      York Heart Association (NYHA) class IV heart failure within 180 days. The key
      safety outcome was stroke within 30 days. RESULTS: The primary outcome occurred
      in 347 of 5033 patients (6.9%) in the thrombectomy group versus 351 of 5030
      patients (7.0%) in the PCI-alone group (hazard ratio in the thrombectomy group,
      0.99; 95% confidence interval [CI], 0.85 to 1.15; P=0.86). The rates of
      cardiovascular death (3.1% with thrombectomy vs. 3.5% with PCI alone; hazard
      ratio, 0.90; 95% CI, 0.73 to 1.12; P=0.34) and the primary outcome plus stent
      thrombosis or target-vessel revascularization (9.9% vs. 9.8%; hazard ratio, 1.00;
      95% CI, 0.89 to 1.14; P=0.95) were also similar. Stroke within 30 days occurred
      in 33 patients (0.7%) in the thrombectomy group versus 16 patients (0.3%) in the
      PCI-alone group (hazard ratio, 2.06; 95% CI, 1.13 to 3.75; P=0.02). CONCLUSIONS:
      In patients with STEMI who were undergoing primary PCI, routine manual
      thrombectomy, as compared with PCI alone, did not reduce the risk of
      cardiovascular death, recurrent myocardial infarction, cardiogenic shock, or NYHA
      class IV heart failure within 180 days but was associated with an increased rate
      of stroke within 30 days. (Funded by Medtronic and the Canadian Institutes of
      Health Research; TOTAL ClinicalTrials.gov number, NCT01149044.).

PMID- 25853746
TI  - Effects of red-cell storage duration on patients undergoing cardiac surgery.
AB  - BACKGROUND: Some observational studies have reported that transfusion of red-cell
      units that have been stored for more than 2 to 3 weeks is associated with
      serious, even fatal, adverse events. Patients undergoing cardiac surgery may be
      especially vulnerable to the adverse effects of transfusion. METHODS: We
      conducted a randomized trial at multiple sites from 2010 to 2014. Participants 12
      years of age or older who were undergoing complex cardiac surgery and were likely
      to undergo transfusion of red cells were randomly assigned to receive leukocyte
      reduced red cells stored for 10 days or less (shorter-term storage group) or for
      21 days or more (longer-term storage group) for all intraoperative and
      postoperative transfusions. The primary outcome was the change in Multiple Organ
      Dysfunction Score (MODS; range, 0 to 24, with higher scores indicating more
      severe organ dysfunction) from the preoperative score to the highest composite
      score through day 7 or the time of death or discharge. RESULTS: The median
      storage time of red-cell units provided to the 1098 participants who received red
      cell transfusion was 7 days in the shorter-term storage group and 28 days in the
      longer-term storage group. The mean change in MODS was an increase of 8.5 and 8.7
      points, respectively (95% confidence interval for the difference, -0.6 to 0.3;
      P=0.44). The 7-day mortality was 2.8% in the shorter-term storage group and 2.0%
      in the longer-term storage group (P=0.43); 28-day mortality was 4.4% and 5.3%,
      respectively (P=0.57). Adverse events did not differ significantly between groups
      except that hyperbilirubinemia was more common in the longer-term storage group.
      CONCLUSIONS: The duration of red-cell storage was not associated with significant
      differences in the change in MODS. We did not find that the transfusion of red
      cells stored for 10 days or less was superior to the transfusion of red cells
      stored for 21 days or more among patients 12 years of age or older who were
      undergoing complex cardiac surgery. (Funded by the National Heart, Lung, and
      Blood Institute; RECESS ClinicalTrials.gov number, NCT00991341.).

PMID- 25853747
TI  - Ibrutinib in previously treated Waldenstrom's macroglobulinemia.
AB  - BACKGROUND: MYD88(L265P) and CXCR4(WHIM) mutations are highly prevalent in
      Waldenstrom's macroglobulinemia. MYD88(L265P) triggers tumor-cell growth through
      Bruton's tyrosine kinase, a target of ibrutinib. CXCR4(WHIM) mutations confer in
      vitro resistance to ibrutinib. METHODS: We performed a prospective study of
      ibrutinib in 63 symptomatic patients with Waldenstrom's macroglobulinemia who had
      received at least one previous treatment, and we investigated the effect of MYD88
      and CXCR4 mutations on outcomes. Ibrutinib at a daily dose of 420 mg was
      administered orally until disease progression or the development of unacceptable
      toxic effects. RESULTS: After the patients received ibrutinib, median serum IgM
      levels decreased from 3520 mg per deciliter to 880 mg per deciliter, median
      hemoglobin levels increased from 10.5 g per deciliter to 13.8 g per deciliter,
      and bone marrow involvement decreased from 60% to 25% (P<0.01 for all
      comparisons). The median time to at least a minor response was 4 weeks. The
      overall response rate was 90.5%, and the major response rate was 73.0%; these
      rates were highest among patients with MYD88(L265P)CXCR4(WT) (with WT indicating
      wild-type) (100% overall response rate and 91.2% major response rate), followed
      by patients with MYD88(L265P)CXCR4(WHIM) (85.7% and 61.9%, respectively) and
      patients with MYD88(WT)CXCR4(WT) (71.4% and 28.6%). The estimated 2-year
      progression-free and overall survival rates among all patients were 69.1% and
      95.2%, respectively. Treatment-related toxic effects of grade 2 or higher
      included neutropenia (in 22% of the patients) and thrombocytopenia (in 14%),
      which were more common in heavily pretreated patients; postprocedural bleeding
      (in 3%); epistaxis associated with the use of fish-oil supplements (in 3%); and
      atrial fibrillation associated with a history of arrhythmia (5%). CONCLUSIONS:
      Ibrutinib was highly active, associated with durable responses, and safe in
      pretreated patients with Waldenstrom's macroglobulinemia. MYD88 and CXCR4
      mutation status affected responses to this drug. (Funded by Pharmacyclics and
      others; ClinicalTrials.gov number, NCT01614821.).

PMID- 25853744
TI  - Surgical ablation of atrial fibrillation during mitral-valve surgery.
AB  - BACKGROUND: Among patients undergoing mitral-valve surgery, 30 to 50% present
      with atrial fibrillation, which is associated with reduced survival and increased
      risk of stroke. Surgical ablation of atrial fibrillation has been widely adopted,
      but evidence regarding its safety and effectiveness is limited. METHODS: We
      randomly assigned 260 patients with persistent or long-standing persistent atrial
      fibrillation who required mitral-valve surgery to undergo either surgical
      ablation (ablation group) or no ablation (control group) during the mitral-valve
      operation. Patients in the ablation group underwent further randomization to
      pulmonary-vein isolation or a biatrial maze procedure. All patients underwent
      closure of the left atrial appendage. The primary end point was freedom from
      atrial fibrillation at both 6 months and 12 months (as assessed by means of 3-day
      Holter monitoring). RESULTS: More patients in the ablation group than in the
      control group were free from atrial fibrillation at both 6 and 12 months (63.2%
      vs. 29.4%, P<0.001). There was no significant difference in the rate of freedom
      from atrial fibrillation between patients who underwent pulmonary-vein isolation
      and those who underwent the biatrial maze procedure (61.0% and 66.0%,
      respectively; P=0.60). One-year mortality was 6.8% in the ablation group and 8.7%
      in the control group (hazard ratio with ablation, 0.76; 95% confidence interval,
      0.32 to 1.84; P=0.55). Ablation was associated with more implantations of a
      permanent pacemaker than was no ablation (21.5 vs. 8.1 per 100 patient-years,
      P=0.01). There were no significant between-group differences in major cardiac or
      cerebrovascular adverse events, overall serious adverse events, or hospital
      readmissions. CONCLUSIONS: The addition of atrial fibrillation ablation to mitral
      valve surgery significantly increased the rate of freedom from atrial
      fibrillation at 1 year among patients with persistent or long-standing persistent
      atrial fibrillation, but the risk of implantation of a permanent pacemaker was
      also increased. (Funded by the National Institutes of Health and the Canadian
      Institutes of Health Research; ClinicalTrials.gov number, NCT00903370.).

PMID- 25853748
TI  - Cancers complicating inflammatory bowel disease.

PMID- 25853749
TI  - Images in clinical medicine. Incisional keloid.

PMID- 25853750
TI  - Case records of the Massachusetts General Hospital. Case 11-2015. A 28-year-old
      woman with headache, fever, and a rash.

PMID- 25853751
TI  - Coronary microvascular obstruction--a puzzle with many pieces.

PMID- 25853752
TI  - Surgical ablation of atrial fibrillation--when, why, and how?

PMID- 25853753
TI  - Gestational hypertension and preeclampsia in living kidney donors.

PMID- 25853754
TI  - Gestational hypertension and preeclampsia in living kidney donors.

PMID- 25853755
TI  - Gestational hypertension and preeclampsia in living kidney donors.

PMID- 25853756
TI  - Gestational hypertension and preeclampsia in living kidney donors.

PMID- 25853745
TI  - Age of transfused blood in critically ill adults.
AB  - BACKGROUND: Fresh red cells may improve outcomes in critically ill patients by
      enhancing oxygen delivery while minimizing the risks of toxic effects from
      cellular changes and the accumulation of bioactive materials in blood components
      during prolonged storage. METHODS: In this multicenter, randomized, blinded
      trial, we assigned critically ill adults to receive either red cells that had
      been stored for less than 8 days or standard-issue red cells (the oldest
      compatible units available in the blood bank). The primary outcome measure was 90
      day mortality. RESULTS: Between March 2009 and May 2014, at 64 centers in Canada
      and Europe, 1211 patients were assigned to receive fresh red cells (fresh-blood
      group) and 1219 patients were assigned to receive standard-issue red cells
      (standard-blood group). Red cells were stored a mean (+/-SD) of 6.1+/-4.9 days in
      the fresh-blood group as compared with 22.0+/-8.4 days in the standard-blood
      group (P<0.001). At 90 days, 448 patients (37.0%) in the fresh-blood group and
      430 patients (35.3%) in the standard-blood group had died (absolute risk
      difference, 1.7 percentage points; 95% confidence interval [CI], -2.1 to 5.5). In
      the survival analysis, the hazard ratio for death in the fresh-blood group, as
      compared with the standard-blood group, was 1.1 (95% CI, 0.9 to 1.2; P=0.38).
      There were no significant between-group differences in any of the secondary
      outcomes (major illnesses; duration of respiratory, hemodynamic, or renal
      support; length of stay in the hospital; and transfusion reactions) or in the
      subgroup analyses. CONCLUSIONS: Transfusion of fresh red cells, as compared with
      standard-issue red cells, did not decrease the 90-day mortality among critically
      ill adults. (Funded by the Canadian Institutes of Health Research and others;
      Current Controlled Trials number, ISRCTN44878718.).

PMID- 25853757
TI  - Esophageal carcinoma.

PMID- 25853758
TI  - Esophageal carcinoma.

PMID- 25853759
TI  - Esophageal carcinoma.

PMID- 25853760
TI  - Esophageal carcinoma.

PMID- 25853761
TI  - Esophageal carcinoma.

PMID- 25853762
TI  - Expanded access to investigational drugs.

PMID- 25853763
TI  - Expanded access to investigational drugs.

PMID- 25853764
TI  - PML in a patient without severe lymphocytopenia receiving dimethyl fumarate.

PMID- 25853765
TI  - PML in a patient with lymphocytopenia treated with dimethyl fumarate.

PMID- 25853766
TI  - Case 26-2014: A 21-month-old boy with lethargy, respiratory distress, and
      abdominal distention.

PMID- 25853767
TI  - Long-term efficacy of a hepatitis E vaccine.

PMID- 25853768
TI  - Images in clinical medicine. Epiglottitis in an adult.

PMID- 25853769
TI  - Interactive medical case. A man with diarrhea and back pain.

PMID- 25853771
TI  - Asymmetric Dearomatization of Naphthols via a Rh-Catalyzed C(sp2)-H
      Functionalization/Annulation Reaction.
AB  - A Rh-catalyzed enantioselective dearomatization of 1-aryl-2-naphthols with
      internal alkynes via C-H functionalization reaction was achieved. In the presence
      of a chiral Cp/Rh catalyst and combined oxidants of Cu(OAc)2 and air (oxygen),
      various highly enantioenriched spirocyclic enones bearing an all-carbon
      quaternary stereogenic center could be synthesized in 33-98% yields with up to
      97:3 er. 

PMID- 25853770
TI  - MK3 modulation affects BMI1-dependent and independent cell cycle check-points.
AB  - Although the MK3 gene was originally found deleted in some cancers, it is highly
      expressed in others. The relevance of MK3 for oncogenesis is currently not clear.
      We recently reported that MK3 controls ERK activity via a negative feedback
      mechanism. This prompted us to investigate a potential role for MK3 in cell
      proliferation. We here show that overexpression of MK3 induces a proliferative
      arrest in normal diploid human fibroblasts, characterized by enhanced expression
      of replication stress- and senescence-associated markers. Surprisingly, MK3
      depletion evokes similar senescence characteristics in the fibroblast model. We
      previously identified MK3 as a binding partner of Polycomb Repressive Complex 1
      (PRC1) proteins. In the current study we show that MK3 overexpression results in
      reduced cellular EZH2 levels and concomitant loss of epigenetic H3K27me3-marking
      and PRC1/chromatin-occupation at the CDKN2A/INK4A locus. In agreement with this,
      the PRC1 oncoprotein BMI1, but not the PCR2 protein EZH2, bypasses MK3-induced
      senescence in fibroblasts and suppresses P16INK4A expression. In contrast, BMI1
      does not rescue the MK3 loss-of-function phenotype, suggesting the involvement of
      multiple different checkpoints in gain and loss of MK3 function. Notably, MK3
      ablation enhances proliferation in two different cancer cells. Finally, the
      fibroblast model was used to evaluate the effect of potential tumorigenic MK3
      driver-mutations on cell proliferation and M/SAPK signaling imbalance. Taken
      together, our findings support a role for MK3 in control of proliferation and
      replicative life-span, in part through concerted action with BMI1, and suggest
      that the effect of MK3 modulation or mutation on M/SAPK signaling and,
      ultimately, proliferation, is cell context-dependent. 

PMID- 25853772
TI  - Comparison of hybrid constructs with 2-level artificial disc replacement and 2
      level anterior cervical discectomy and fusion for surgical reconstruction of the
      cervical spine: a kinematic study in whole cadavers.
AB  - BACKGROUND: Multi-level cervical degeneration of the spine is a common clinical
      pathology that is often repaired by anterior cervical discectomy and fusion
      (ACDF). The aim of this study was to investigate the kinematics of the cervical
      spine after hybrid surgery compared with 2-level ACDF. MATERIAL AND METHODS: Five
      freshly frozen, unembalmed whole human cadavers were used including 3 males and 2
      females with a mean age of 51 +/- 8 years. After evaluating the intact spine for
      range of motion (ROM), sagittal alignment and instantaneous center of rotation
      (ICR), each cadaver underwent 4 consecutive surgeries: 2-level artificial disc
      replacement (ADR) from C4 to C6 (ADR surgery); 2-level ACDF from C4 to C6 (ACDF
      surgery); hybrid C4-5 ACDF and C5-6 ADR (ACDF+ADR surgery); and hybrid C4-5 ADR
      and C5-6 ACDF (ADR+ACDF surgery). The ROM and ICR of adjacent intact segments (C3
      4; C6-7), and whole sagittal alignment were revaluated. RESULTS: Two-level ACDF
      resulted in increased ROM at C3-4 and C6-7 compared with intact spine. ROM was
      significantly different to intact spine using ACDF surgery at C3-C4 and C6-C7 and
      ROM was increased with ACDF+ADR surgery at C6-C7 (all P<0.05). No improvement in
      sagittal alignment was observed with any approach. The localization of the ICR
      shifted upwards and anteriorly at C3-C4 after reconstruction. ICR changes at C3
      C4 were greatest for ADR+ACDF surgery and were significantly different to ACDF
      surgery (P<0.05), but not between ADR surgery and ACDF+ADR surgery. At C6-C7, the
      ICR was more posterior and superior than in the intact condition. The greatest
      change in ICR was observed in ACDF surgery at the C6-C7 level, significantly
      different from the other groups (P<0.05). CONCLUSIONS: For 2-level
      reconstruction, hybrid surgery and ADR did not alter ROM and minimally changed
      ICR at the adjacent-level. The type of surgery had a significant impact on the
      ICR location. This suggests that hybrid surgery may be a viable option for 2
      level cervical surgery.

PMID- 25853774
TI  - Assessment of Low-Contrast Resolution for the American College of Radiology
      Computed Tomographic Accreditation Program: What Is the Impact of Iterative
      Reconstruction?
AB  - OBJECTIVE: To compare contrast-to-noise ratio (CNR) thresholds with visual
      assessment of low-contrast resolution (LCR) in filtered back projection (FBP) and
      iteratively reconstructed (IR) computed tomographic (CT) images. METHODS:
      American College of Radiology (ACR) CT accreditation phantom LCR images were
      acquired at CTDIvol levels of 8, 12, and 16 mGy using 2 scanner models and
      reconstructed using one FBP and 2 IR kernels. Acquisitions were repeated 100
      times. Three board-certified medical physicists blindly reviewed the LCR section
      images. Pass-percentage rates (PPRs) using previous and current ACR CT
      accreditation criteria were compared. RESULTS: Observer PPRs for FBP images were
      less than 32%. For IR images, 5 of 18 settings/dose/model configurations had PPRs
      greater than 32% (maximum 76.3%). For CNR evaluation of FBP images, PPRs for 15
      configurations were greater than 70%. For IR images, all PPRs were at least 96%.
      CONCLUSIONS: The CNR threshold used by the ACR CT accreditation program yields
      higher PPRs than visual assessment of LCR, potentially resulting in lower-quality
      images passing the ACR CNR criteria.

PMID- 25853775
TI  - Graft Kidney Torsion After Simultaneous Kidney-Pancreas Transplant: Report of 2
      Cases and Literature Review.
AB  - Torsion of an allograft kidney is an extremely rare and potentially reversible
      complication. Imaging diagnosis plays a crucial role because of the absence of
      specific clinical features. We report 2 cases in which kidney torsion after
      simultaneous kidney-pancreas transplant was diagnosed by ferumoxytol-enhanced
      magnetic resonance imaging/angiography and present a review of the relevant
      literature. Radiologists and clinicians should be aware of this entity because
      graft salvage depends on rapid diagnosis and surgical detorsion. 

PMID- 25853776
TI  - Automatic Brain Portion Segmentation From Magnetic Resonance Images of Head Scans
      Using Gray Scale Transformation and Morphological Operations.
AB  - OBJECTIVE: To develop an automatic skull stripping method for magnetic resonance
      imaging (MRI) of human head scans. METHODS: The proposed method is based on gray
      scale transformation and morphological operations. RESULTS: The proposed method
      has been tested with 20 volumes of normal T1-weighted images taken from Internet
      Brain Segmentation Repository. Experimental results show that the proposed method
      gives better results than the popular skull stripping methods Brain Extraction
      Tool and Brain Surface Extractor. The average value of Jaccard and Dice
      coefficients are 0.93 and 0.962 respectively. CONCLUSIONS: In this article, we
      have proposed a novel skull stripping method using intensity transformation and
      morphological operations. This is a low computational complexity method but gives
      competitive or better results than that of the popular skull stripping methods
      Brain Surface Extractor and Brain Extraction Tool.

PMID- 25853777
TI  - Validity of measurement of shear modulus by ultrasound shear wave elastography in
      human pennate muscle.
AB  - Ultrasound shear wave elastography is becoming a valuable tool for measuring
      mechanical properties of individual muscles. Since ultrasound shear wave
      elastography measures shear modulus along the principal axis of the probe (i.e.,
      along the transverse axis of the imaging plane), the measured shear modulus most
      accurately represents the mechanical property of the muscle along the fascicle
      direction when the probe's principal axis is parallel to the fascicle direction
      in the plane of the ultrasound image. However, it is unclear how the measured
      shear modulus is affected by the probe angle relative to the fascicle direction
      in the same plane. The purpose of the present study was therefore to examine
      whether the angle between the principal axis of the probe and the fascicle
      direction in the same plane affects the measured shear modulus. Shear modulus in
      seven specially-designed tissue-mimicking phantoms, and in eleven human in-vivo
      biceps brachii and medial gastrocnemius were determined by using ultrasound shear
      wave elastography. The probe was positioned parallel or 20 degrees  obliquely to
      the fascicle across the B-mode images. The reproducibility of shear modulus
      measurements was high for both parallel and oblique conditions. Although there
      was a significant effect of the probe angle relative to the fascicle on the shear
      modulus in human experiment, the magnitude was negligibly small. These findings
      indicate that the ultrasound shear wave elastography is a valid tool for
      evaluating the mechanical property of pennate muscles along the fascicle
      direction. 

PMID- 25853780
TI  - Microbiome: Taking advantage of quorum sensing.

PMID- 25853778
TI  - Urinary tract infections: epidemiology, mechanisms of infection and treatment
      options.
AB  - Urinary tract infections (UTIs) are a severe public health problem and are caused
      by a range of pathogens, but most commonly by Escherichia coli, Klebsiella
      pneumoniae, Proteus mirabilis, Enterococcus faecalis and Staphylococcus
      saprophyticus. High recurrence rates and increasing antimicrobial resistance
      among uropathogens threaten to greatly increase the economic burden of these
      infections. In this Review, we discuss how basic science studies are elucidating
      the molecular details of the crosstalk that occurs at the host-pathogen
      interface, as well as the consequences of these interactions for the
      pathophysiology of UTIs. We also describe current efforts to translate this
      knowledge into new clinical treatments for UTIs. 

PMID- 25853781
TI  - Bacterial evolution: Cutting out the carBs feeds a bistable switch.

PMID- 25853779
TI  - Recent functional insights into the role of (p)ppGpp in bacterial physiology.
AB  - The alarmones guanosine tetraphosphate and guanosine pentaphosphate (collectively
      referred to as (p)ppGpp) are involved in regulating growth and several different
      stress responses in bacteria. In recent years, substantial progress has been made
      in our understanding of the molecular mechanisms of (p)ppGpp metabolism and
      (p)ppGpp-mediated regulation. In this Review, we summarize these recent insights,
      with a focus on the molecular mechanisms governing the activity of the RelA/SpoT
      homologue (RSH) proteins, which are key players that regulate the cellular levels
      of (p)ppGpp. We also discuss the structural basis of transcriptional regulation
      by (p)ppGpp and the role of (p)ppGpp in GTP metabolism and in the emergence of
      bacterial persisters. 

PMID- 25853782
TI  - [Objective Criteria in the Medicinal Therapy for Type II Diabetes: An Analysis of
      the Patients' Perspective with Analytic Hierarchy Process and Best-Worst
      Scaling].
AB  - BACKGROUND: The patient's perspective with regard to decision criteria of
      alternative treatment options has hardly been analysed. The objective of any
      intervention in health-care is to increase the patient's benefit. OBJECTIVE: This
      study aimed to analyse the patient-relevant decision criteria in the medicinal
      therapy of type II diabetes. The characteristics of a drug therapy that are
      relevant for the choice of the patients should be revealed. METHOD: An
      explorative qualitative study (N=15) in combination with a quantitative survey
      (in total N=388) using Analytic Hierarchy Process and Best-Worst Scaling aimed at
      the determination of the importance of patient-relevant decision criteria.
      RESULTS: The quantitative AHP- and BWS survey resulted in a clear dominance of
      the attribute "HbA1c level" and its optimal settings, for both with oral anti
      diabetics treated patients (OAD) and insulin-treated patients. In the group of
      the OAD patients both methods independently showed the same ranking of the
      following 3 ranks: "delay of insulin therapy" (rank 2), "occurrence of
      hypoglycaemia" (rank 3) and "weight changes" (rank 4). For insulin patients "the
      occurrence of hypoglycaemia" follows in the AHP on the second rank and in the BWS
      on the 3(rd) rank. Compared to OAD patients, the relevance of the target
      criterion "weight changes" decreases in the group of the insulin patients in the
      AHP on the last rank (rank 7) and in the BWS on the second last rank (rank 6).
      CONCLUSION: For the first time the methods of AHP and BWS were combined to assess
      how patients weight between different characteristics of the treatment in type II
      diabetes and which influence those criteria of therapy have on the patient's
      benefit. Both patient groups show differences in the horizon of experience and
      thus in the ranking of the decision criteria.

PMID- 25853784
TI  - From the editor.

PMID- 25853783
TI  - Electrochemical fabrication of graphene nanomesh via colloidal templating.
AB  - A simple electrochemical fabrication of graphene nanomesh (GNM) via colloidal
      templating is reported for the first time. The process involves the arraying of
      polystyrene (PS) spheres onto a CVD-deposited graphene, electro-deposition of
      carbazole units, removal of the PS template and electrochemical oxidative
      etching. The GNM was characterized by scanning electron microscopy (SEM), atomic
      force microscopy (AFM) and Raman spectroscopy. 

PMID- 25853785
TI  - Older women with intellectual disability and the meaning of aging.
AB  - Aging with intellectual disability has become an important topic in light of the
      significant increase in life expectancy of this population. More specifically,
      the combination of gender, age, and intellectual disability raises unique social
      issues. The aim of this research was to capture and analyze the aging experience
      of women with intellectual disability from their own voice and viewpoint within
      the Israeli experience. A phenomenological qualitative method was used in this
      study. In-depth interviews were conducted with 19 women with mild-to-moderate
      intellectual disability. Four key themes arose from the interviews: (a) the
      importance of work and reluctance to retire, (b) ageism and the fear of getting
      old, (c) the importance of a significant partner in old age, and (d) today's
      positive self-perception. A meaningful aging process can be constructed within
      the context of gender and disability. It was manifested in this study as a
      disability-neutral experience. However, ageism and negative attitudes toward old
      age still need to be addressed. 

PMID- 25853788
TI  - Prurigo Pigmentosa After Bariatric Surgery.

PMID- 25853789
TI  - Ability of wild type mouse bioassay to detect bovine spongiform encephalopathy
      (BSE) in the presence of excess scrapie.
AB  - INTRODUCTION: Scrapie and bovine spongiform encephalopathy (BSE) are
      transmissible spongiform encephalopathies (TSEs) which naturally affect small and
      large ruminants respectively. However, small ruminants, which are susceptible to
      BSE under experimental conditions, have been exposed to the same or similar
      contaminated food additives as cattle. To date two natural cases of BSE in small
      ruminants have been reported. As a result surveillance projects, combined with
      appropriate control measures, have been established throughout the European Union
      (EU) to minimize the overall incidence of small ruminant TSEs. Although BSE can
      be differentiated from classical scrapie (subsequently referred to as scrapie) if
      appropriate discriminatory tests are applied, the value of these tests in
      BSE/scrapie co-infection scenarios has not been evaluated fully. Mouse bioassay
      is regarded as the gold standard regarding differentiation of distinct TSE
      strains and has been used as to resolve TSE cases were laboratory tests produced
      equivocal results. However, the ability of this method to discriminate TSE
      strains when they co-exist has not been examined systematically. To address this
      issue we prepared in vitro mixtures of ovine BSE and scrapie and used them to
      challenge RIII, C57BL/6 and VM mice. RESULTS: Disease phenotype analysis in all
      three mouse lines indicated that most phenotypic parameters (attack rates,
      incubation periods, lesion profiles and Western blots) were compatible with
      scrapie phenotypes as were immunohistochemistry (IHC) data from RIII and C57BL/6
      mice. However, in VM mice that were challenged with BSE/scrapie mixtures a single
      BSE-associated IHC feature was identified, indicating the existence of BSE in
      animals where the scrapie phenotype was dominant. CONCLUSIONS: We conclude that
      wild type mouse bioassay is of limited value in detecting BSE in the presence of
      scrapie particularly if the latter is in relative excess.

PMID- 25853790
TI  - 1',5'-Anhydro-L-ribo-hexitol Adenine Nucleic Acids (alpha-L-HNA-A): Synthesis and
      Chiral Selection Properties in the Mirror Image World.
AB  - The synthesis and a preliminary investigation of the base pairing properties of
      (6' -> 4')-linked 1',5'-anhydro-L-ribo-hexitol nucleic acids (alpha-L-HNA) have
      herein been reported through the study of a model oligoadenylate system in the
      mirror image world. Despite its considerable preorganization due to the rigidity
      of the "all equatorial" pyranyl sugar backbone, alpha-L-HNA represents a
      versatile informational biopolymer, in view of its capability to cross
      communicate with natural and unnatural complements in both enantiomeric forms.
      This seems the result of an inherent flexibility of the oligonucleotide system,
      as witnessed by the singular formation of iso- and heterochiral associations
      composed of regular, enantiomorphic helical structures. The peculiar properties
      of alpha-L-HNA (and most generally of the alpha-HNA system) provide new elements
      in our understanding of the structural prerequisites ruling the stereoselectivity
      of the hybridization processes of nucleic acids.

PMID- 25853791
TI  - Impact of PACAP and PAC1 receptor deficiency on the neurochemical and behavioral
      effects of acute and chronic restraint stress in male C57BL/6 mice.
AB  - Acute restraint stress (ARS) for 3 h causes corticosterone (CORT) elevation in
      venous blood, which is accompanied by Fos up-regulation in the paraventricular
      nucleus (PVN) of male C57BL/6 mice. CORT elevation by ARS is attenuated in PACAP
      deficient mice, but unaffected in PAC1-deficient mice. Correspondingly, Fos up
      regulation by ARS is greatly attenuated in PACAP-deficient mice, but much less so
      in PAC1-deficient animals. We noted that both PACAP- and PAC1-deficiency greatly
      attenuate CORT elevation after ARS when CORT measurements are performed on trunk
      blood following euthanasia by abrupt cervical separation: this latter observation
      is of critical importance in assessing the role of PACAP neurotransmission in
      ARS, based on previous reports in which serum CORT was sampled from trunk blood.
      Seven days of chronic restraint stress (CRS) induces non-habituating CORT
      elevation, and weight loss consequent to hypophagia, in wild-type male C57BL/6
      mice. Both CORT elevation and weight loss following 7-day CRS are severely
      blunted in PACAP-deficient mice, but only slightly in PAC1-deficient mice.
      However, longer periods of daily restraint (14-21 days) resulted in sustained
      weight loss and elevated CORT in wild-type mice, and these effects of long-term
      chronic stress were attenuated or abolished in both PACAP- and PAC1-deficient
      mice. We conclude that while a PACAP receptor in addition to PAC1 may mediate
      some of the PACAP-dependent central effects of ARS and short-term (<7 days) CRS
      on the hypothalamo-pituitary-adrenal (HPA) axis, the PAC1 receptor plays a
      prominent role in mediating PACAP-dependent HPA axis activation, and hypophagia,
      during long-term (>7 days) CRS. 

PMID- 25853792
TI  - Inflammatory and cardiometabolic risk on obesity: role of environmental
      xenoestrogens.
AB  - CONTEXT: Some chemicals used in consumer products or manufacturing (eg, plastics,
      pesticides) have estrogenic activities; these xenoestrogens (XEs) may affect
      immune responses and have recently emerged as a new risk factors for obesity and
      cardiovascular disease. However, the extent and impact on health of chronic
      exposure of the general population to XEs are still unknown. OBJECTIVE: The
      objective of the study was to investigate the levels of XEs in plasma and adipose
      tissue (AT) depots in a sample of pre- and postmenopausal obese women undergoing
      bariatric surgery and their cardiometabolic impact in an obese state. DESIGN AND
      PARTICIPANTS: We evaluated XE levels in plasma and visceral and subcutaneous AT
      samples of Portuguese obese (body mass index >= 35 kg/m(2)) women undergoing
      bariatric surgery. Association with metabolic parameters and 10-year
      cardiovascular disease risk was assessed, according to menopausal status (73 pre-
      and 48 postmenopausal). Levels of XEs were determined by gas chromatography with
      electron-capture detection. Anthropometric and biochemical data were collected
      prior to surgery. Adipocyte size was determined on tissue sections obtained
      during surgery. RESULTS: Our data show that XEs are pervasive in this obese
      population. Distribution of individual and concentration of total XEs differed
      between plasma, visceral AT, and subcutaneous AT, and the pattern of accumulation
      was different between pre- and postmenopausal women. Significant associations
      between XE levels and metabolic and inflammatory parameters were found. In
      premenopausal women, XEs in plasma seem to be a predictor of 10-year
      cardiovascular disease risk. CONCLUSIONS: Our findings point toward a different
      distribution of XE between plasma and AT in pre- and postmenopausal women, and
      reveal the association between XEs on the development of metabolic abnormalities
      in obese premenopausal women.

PMID- 25853793
TI  - ARMC5 Mutations in a Large Cohort of Primary Macronodular Adrenal Hyperplasia:
      Clinical and Functional Consequences.
AB  - CONTEXT: Primary bilateral macronodular adrenal hyperplasia (PBMAH) is a rare
      cause of primary adrenal Cushing's syndrome (CS). ARMC5 germline mutations have
      been identified recently in PBMAH. OBJECTIVE: To determine the prevalence of
      ARMC5 mutations and analyze genotype-phenotype correlation in a large cohort of
      unrelated PBMAH patients with subclinical or clinical CS. PATIENTS AND METHODS:
      ARMC5 was sequenced in 98 unrelated PBMAH index cases. PBMAH was identified by
      bilateral adrenal nodular enlargement on computed tomography scan. The effect on
      apoptosis of ARMC5 missense mutants was tested in H295R and HeLa cells. Clinical
      and hormonal data were collected including midnight and urinary free cortisol
      levels, ACTH, androgens, renin/aldosterone ratio, cortisol after overnight
      dexamethasone suppression test, cortisol and 17-hydroxyprogesterone after ACTH 1
      24 stimulation and illegitimate receptor responses. Computed tomography and
      histological reports were analyzed. RESULTS: ARMC5-damaging mutations were
      identified in 24 patients (26%). The missense mutants and the p.F700del deletion
      were unable to induce apoptosis in both H295R and HeLa cell lines, unlike the
      wild-type gene. ARMC5-mutated patients showed an overt CS more frequently,
      compared to wild-type patients: lower ACTH, higher midnight plasma cortisol,
      urinary free cortisol, and cortisol after dexamethasone suppression test (P =
      .003, .019, .006, and <.001, respectively). Adrenals of patients with mutations
      were bigger and had a higher number of nodules (P = .001 and <.001,
      respectively). CONCLUSIONS: ARMC5 germline mutations are common in PBMAH. Index
      cases of mutation carriers show a more severe hypercortisolism and larger
      adrenals. ARMC5 genotyping may help to identify clinical forms of PBMAH better
      and may also allow earlier diagnosis of this disease.

PMID- 25853794
TI  - A photochromic sensor microchip for high-performance multiplex metal ions
      detection.
AB  - Current multi-analytes chips are limited with requiring numbers of sensors,
      complex synthesis and compounds screen. It is expected to develop new principles
      and techniques to achieve high-performance multi-analytes testing with facile
      sensors. Here, we investigated the correlative multi-states properties of a
      photochromic sensor (spirooxazine), which is capable of a selective and cross
      reactive sensor array for discriminated multi-analytes (11 metal ions) detection
      by just one sensing compound. The multi-testing sensor array performed in dark,
      ultraviolet or visual stimulation, corresponding to different molecular states of
      spirooxazine metal ions coordination. The facile photochromic microchip
      contributes a multi-states array sensing method, and will open new opportunities
      for the development of advanced discriminant analysis for complex analytes. 

PMID- 25853795
TI  - A multi-center randomized controlled trial to compare a self-ligating bracket
      with a conventional bracket in a UK population: Part 1: Treatment efficiency.
AB  - OBJECTIVE: To use a two-arm parallel trial to compare treatment efficiency
      between a self-ligating and a conventional preadjusted edgewise appliance system.
      MATERIALS AND METHODS: A prospective multi-center randomized controlled clinical
      trial was conducted in three hospital orthodontic departments. Subjects were
      randomly allocated to receive treatment with either a self-ligating (3M
      SmartClip) or conventional (3M Victory) preadjusted edgewise appliance bracket
      system using a computer-generated random sequence concealed in opaque envelopes,
      with stratification for operator and center. Two operators followed a
      standardized protocol regarding bracket bonding procedure and archwire sequence.
      Efficiency of each ligation system was assessed by comparing the duration of
      treatment (months), total number of appointments (scheduled and emergency
      visits), and number of bracket bond failures. RESULTS: One hundred thirty-eight
      subjects (mean age 14 years 11 months) were enrolled in the study, of which 135
      subjects (97.8%) completed treatment. The mean treatment time and number of
      visits were 25.12 months and 19.97 visits in the SmartClip group and 25.80 months
      and 20.37 visits in the Victory group. The overall bond failure rate was 6.6% for
      the SmartClip and 7.2% for Victory, with a similar debond distribution between
      the two appliances. No significant differences were found between the bracket
      systems in any of the outcome measures. No serious harm was observed from either
      bracket system. CONCLUSIONS: There was no clinically significant difference in
      treatment efficiency between treatment with a self-ligating bracket system and a
      conventional ligation system.

PMID- 25853796
TI  - Impact of wearing fixed orthodontic appliances on quality of life among
      adolescents: Case-control study.
AB  - OBJECTIVE: To investigate the impact of wearing a fixed orthodontic appliance on
      oral health-related quality of life (OHRQoL) among adolescents. MATERIALS AND
      METHODS: A case-control study (1 ? 2) was carried out with a population-based
      randomized sample of 327 adolescents aged 11 to 14 years enrolled at public and
      private schools in the City of Brumadinho, southeast of Brazil. The case group (n
      =  109) was made up of adolescents with a high negative impact on OHRQoL, and
      the control group (n  =  218) was made up of adolescents with a low negative
      impact. The outcome variable was the impact on OHRQoL measured by the Brazilian
      version of the Child Perceptions Questionnaire (CPQ 11-14) - Impact Short Form
      (ISF:16). The main independent variable was wearing fixed orthodontic appliances.
      Malocclusion and the type of school were identified as possible confounding
      variables. Bivariate and multiple conditional logistic regressions were employed
      in the statistical analysis. RESULTS: A multiple conditional logistic regression
      model demonstrated that adolescents wearing fixed orthodontic appliances had a
      4.88-fold greater chance of presenting high negative impact on OHRQoL (95% CI:
      2.93-8.13; P < .001) than those who did not wear fixed orthodontic appliances. A
      bivariate conditional logistic regression demonstrated that malocclusion was
      significantly associated with OHRQoL (P  =  .017), whereas no statistically
      significant association was found between the type of school and OHRQoL (P  = 
      .108). CONCLUSIONS: Adolescents who wore fixed orthodontic appliances had a
      greater chance of reporting a negative impact on OHRQoL than those who did not
      wear such appliances.

PMID- 25853797
TI  - The ONIOM Method and Its Applications.

PMID- 25853798
TI  - Influence of Immunogenicity of Allogeneic Bone Marrow Mesenchymal Stem Cells on
      Bone Tissue Engineering.
AB  - Allogeneic bone marrow mesenchymal stem cell (allo-BMSC)-based tissue-engineered
      bone (TEB) has great potential for bone defect repair. However, the
      immunogenicities and biological roles of allo-BMSCs are still controversial. In
      this study, we established an animal model of critical-sized mandibular defect in
      beagle dogs and compared the repairing effects of allo-BMSC-based TEB with
      autogenic BMSC (auto-BMSC)-based TEB without the administration of
      immunosuppressants. During the first 2 weeks postimplantation, a transient immune
      response in the allo-BMSC group was detected with an increase in proinflammation
      cytokines TNF-alpha, IFN-gamma, and IL-2, a declination of anti-inflammation
      cytokine IL-10, and an increase in percentages of CD4(+) and CD8(+) T-cell
      subsets in peripheral blood. Nevertheless, there was no significant difference in
      bone union achievement, bone mineral density, and biomechanical properties
      between the two groups at 12 and 24 weeks postimplantation. Further subcutaneous
      implantation of allo-BMSCs/scaffold also exhibited the similar transient immune
      responses in the first 2 weeks postimplantation but followed by a decreased bone
      formation at 4 and 8 weeks postimplantation. These findings indicate that allo
      BMSCs can induce a transient immunoreaction, which may temporally delay the
      osteogenesis of allo-BMSC/scaffold complex in early stage of in vivo
      implantation, whereas the long-term engineered bone formation was not affected. 

PMID- 25853801
TI  - Ruling out coronary artery disease in women with atypical chest pain: results of
      calcium score combined with coronary computed tomography angiography and
      associated radiation exposure.
AB  - BACKGROUND: To assess the presence of coronary artery disease (CAD) in women with
      atypical chest pain with low or intermediate risk for significant CAD by means of
      calcium scoring (CaSc) combined with coronary computed tomography angiography
      (CCTA) and to estimate the equivalent radiation dose in women. PATIENTS AND
      METHODS: From December 2011 until July 2013, all consecutively performed cardiac
      CTs in women with atypical chest pain were included prospectively in the present
      study. Both CaSc and CCTA were obtained by a dual source flying focal spot 2*64
      slice Somatom Definition Flash. Absence of CAD was defined as CaSc 0 and absence
      of noncalcified plaques. Presence of CAD was determined as CaSc>0 and/or presence
      of noncalcified plaques. The impact on patient management was also scored within
      our patient cohort. RESULTS: A total of 1033 procedures in 1014 women (mean age
      59+/-10 years; mean BMI 26+/-8) were analyzed. In 520 (51%) women, CAD was
      absent. In 494 (49%) women, CAD was diagnosed, and in this subgroup the mean CaSc
      was 137+/-229. Thirty-seven (7%) of 494 women with CAD showed only noncalcified
      plaques. The mean equivalent radiation dose for the cardiac CTs of 1014 women was
      2.2+/-1.6 mSv. CONCLUSION: Combined CaSc and CCTA excludes CAD in approximately
      50% of women with atypical chest pain, and delivers a modest radiation dose of
      2.2+/-1.6 mSv. CCTA has a substantial impact on patient management and can thus
      be advocated as first diagnostic tool in excluding CAD in women with atypical
      chest pain in terms of latest generation equipment with emphasize on radiation
      reduction techniques.

PMID- 25853800
TI  - 5-hydroxymethylcytosine marks promoters in colon that resist DNA hypermethylation
      in cancer.
AB  - BACKGROUND: The discovery of cytosine hydroxymethylation (5hmC) as a mechanism
      that potentially controls DNA methylation changes typical of neoplasia prompted
      us to investigate its behaviour in colon cancer. 5hmC is globally reduced in
      proliferating cells such as colon tumours and the gut crypt progenitors, from
      which tumours can arise. RESULTS: Here, we show that colorectal tumours and
      cancer cells express Ten-Eleven-Translocation (TET) transcripts at levels similar
      to normal tissues. Genome-wide analyses show that promoters marked by 5hmC in
      normal tissue, and those identified as TET2 targets in colorectal cancer cells,
      are resistant to methylation gain in cancer. In vitro studies of TET2 in cancer
      cells confirm that these promoters are resistant to methylation gain
      independently of sustained TET2 expression. We also find that a considerable
      number of the methylation gain-resistant promoters marked by 5hmC in normal colon
      overlap with those that are marked with poised bivalent histone modifications in
      embryonic stem cells. CONCLUSIONS: Together our results indicate that promoters
      that acquire 5hmC upon normal colon differentiation are innately resistant to
      neoplastic hypermethylation by mechanisms that do not require high levels of 5hmC
      in tumours. Our study highlights the potential of cytosine modifications as
      biomarkers of cancerous cell proliferation.

PMID- 25853802
TI  - Proliferation of axial parenchymatic xylem cells is a key step in wound closure
      of girdled stems in Pinus canariensis.
AB  - BACKGROUND: Wounds caused by fire, herbivorism, rock impacts, etc. cause the
      direct loss of photosynthetic, storage and/or vascular tissue. In addition, they
      may entail other damages, such as desiccation of the exposed internal parts, or
      become a gateway to infection by fungi and other pathogens. To successfully
      overcome such injuries, plants must reorganize their meristems or even
      differentiate new ones, producing new traumatic tissues to cover the wound and
      restore the vascular connection. RESULTS: In this work we analyse the anatomical
      growth response in conifers after debarking and injuring the vascular cambium,
      using Pinus canariensis as model species, due to its high wound recovery ability.
      Conversely to angiosperm woody species, this process is initiated and largely
      driven by the damaged vascular cambium and not by proliferation in the wound
      surface. We have detected alterations and switches in the divisions of cambial
      cells, associated to their position relative to the surface and edges of the
      wound, resulting in disordered traumatic xylem. We also describe the formation of
      column-like structures, after girdling, which are in part formed by the
      proliferation of xylem parenchymatous cells, associated to axial resin ducts.
      CONCLUSIONS: Abundant resinosis on the wound surface, typical of conifers, is an
      efficient barrier against opportunistic fungi, insects, etc. but it also hinders
      the healing process directly from the surface. Thus, wound closure must be
      largely carried out from the wound margins, being a much slower process, which
      very often remains unconcluded for long years. This work also describes for the
      first time the proliferation of inner parenchymatous cells to form column-like
      structures, which accelerates wound closure in girdled P. canariensis.
      Irregularities in the surface of the healing edge or column-like structures
      result in the production of disordered vascular tissues, compromising their
      future functionality, and which must be overcome through the fast restoration of
      the proper polarity in vascular cambium.

PMID- 25853803
TI  - Marked seasonality and high spatial variability of protist communities in shallow
      freshwater systems.
AB  - Small eukaryotes have key roles in aquatic ecosystems, influencing their local
      environment, global biogeochemical cycles and climate. Their impact depends on
      community structure, which varies along time. However, very few studies take into
      account temporal variation. This is especially true for small, shallow freshwater
      systems, which remain largely understudied despite their wide variety, global
      surface and intense microbial activity. We have monthly followed changes in the
      community structure of small microbial eukaryotes (0.2-5 MUm cell diameter) for 2
      years in four ponds and one brook located in North-Western France based on
      massive 18S rDNA amplicon 454 pyrosequencing. We detected a total of 3742
      stringently defined operational taxonomic units (OTUs) encompassing all
      recognized eukaryotic supergroups and lineages of uncertain affiliation. Although
      geographically close, protist communities in the five ecosystems were
      contrasting, with very few shared OTUs, suggesting that environmental selection
      mainly drives community structure. The temporal dynamics of different high-rank
      taxa appeared complex and rapid at monthly scales. Despite this, a clear and
      reproducible seasonality was observed. As expected, low-abundance OTUs dominated
      the community. Although some of them appeared sporadically or remained at low
      frequencies during the survey, others occasionally reached relatively high
      abundances, sometimes recurrently. This shows that at least a fraction of low
      abundance eukaryotes constitutes a seed bank. The annual proportion of primary
      producers, free-living heterotrophs and parasites appeared remarkably constant
      among the different ecosystems, suggesting underlying trends of ecosystem
      carrying capacity for these functional groups.

PMID- 25853804
TI  - alpha2u-globulins mediate manipulation of host attractiveness in Toxoplasma
      gondii-Rattus novergicus association.
AB  - Uninfected female rats (Rattus novergicus) exhibit greater attraction to the
      males infected with protozoan parasite Toxoplasma gondii. This phenomenon is
      contrary to the aversion towards infected males observed in multitude of other
      host-parasite associations. In this report, we describe a proximate mechanism for
      this anomaly. We demonstrate that T. gondii infection enhances hepatic production
      and urinary excretion of alpha2u-globulins in rats. We further demonstrate that
      alpha2u-globulins are sufficient to recapitulate male sexual attractiveness akin
      to effects of the infection. This manipulation possibly results in greater
      horizontal transmission of this parasite between the infected male and the
      uninfected female. It supports the notion that in some evolutionary niches
      parasites can alter host sexual signaling, likely leading to an increased rate of
      sexual transmission. 

PMID- 25853805
TI  - The Trigger Tool as a Method to Measure Harmful Medication Errors in Children.
AB  - OBJECTIVES: The aim of this study was to improve medication safety for children;
      it is important to quantify the occurrence of preventable medication errors
      (MEs). A trigger tool may be an effective and time-saving strategy, but its
      measurement performance is unclear. Therefore, we aimed to estimate the
      performance of a pediatric medication-focused trigger tool in detecting harmful
      MEs. METHODS: First, we established a multifaceted method as a reference
      comparison. Second, we compared the pediatric medication-focused trigger tool
      with the multifaceted method in a new cohort of patients. All patients admitted
      in February and March 2013 were screened using the trigger tool and the
      multifaceted method to obtain full verification. Data collection was performed in
      separate teams to guarantee blinding of the test results. RESULTS: Review of the
      clinical records and the voluntary incident reports was most effective in
      detecting harmful MEs, so this approach was chosen as a reference comparison. In
      the second part of the study, 369 patients were included. The multifaceted method
      identified 33 harmful MEs. In contrast, the trigger tool did not identify any
      harm. When the 2 symptoms pain and nausea/vomiting were added to the trigger
      tool, 19 harmful MEs were identified. This extended trigger tool resulted in a
      sensitivity of 21.2 and a positive predictive value of 36.8. CONCLUSIONS: The
      original pediatric medication-focused trigger tool yielded only false-positive
      scores and left unsafe situations undiscovered. We conclude that a multifaceted
      method remains the preferred method to detect harmful MEs. The additional value
      of the trigger tool stays unclear.

PMID- 25853806
TI  - Evaluation of the Prevalence of Shielding in Patients Undergoing Conventional
      Radiological Procedures (1 Work Shift-1 X-ray Room).
AB  - OBJECTIVES: This study aimed to evaluate the prevalence of shielding in patients
      undergoing conventional radiological procedures (1 work shift-1 x-ray room).The
      increased number of patients undergoing x-ray examinations has created a global
      concern due to the stochastic and nonstochastic association with x-ray exposure.
      Shielding is an efficient method of protecting radiosensitive organs when
      performing radiological examinations. MATERIALS AND METHODS: Thirty radiography
      students were sent to conventional radiology departments to act as observers in
      the control booth of an x-ray room when a radiological procedure was being
      performed. RESULTS: Of the 30 hospitals evaluated, 13% regarded shielding of
      radiosensitive organs. The prevalence of shielding in the hospitals where
      shielding of radiosensitive organs was implemented varied from 5.2% to 14%.
      CONCLUSION: The results of this study showed that shielding of radiosensitive
      organs was not performed in the majority of hospitals. More studies are needed to
      establish the potential causes of low shielding prevalence.If these findings,
      which were obtained over 1 work shift and in 1 x-ray room, are representative of
      a large number of medical imaging centers, this raises global concerns regarding
      shielding of radiosensitive organs, in particular gonad shielding.

PMID- 25853807
TI  - Complications of Non-Operating Room Procedures: Outcomes From the National
      Anesthesia Clinical Outcomes Registry.
AB  - OBJECTIVES: This study examines the impact of procedural locations and types of
      anesthetics on patient outcomes in non-operating room anesthesia (NORA)
      locations. The National Anesthesia Clinical Outcomes Registry database was
      examined to compare OR to NORA anesthetic complications and patient demographics.
      METHODS: The National Anesthesia Clinical Outcomes Registry database was examined
      for all patient procedures from 2010 to 2013. A total of 12,252,846 cases were
      analyzed, with 205 practices contributing information, representing 1494
      facilities and 7767 physician providers. Cases were separated on the basis of
      procedure location, OR, or NORA. Subgroup analysis examined outcomes from
      specific subspecialties. RESULTS: Non-OR anesthesia procedures were performed on
      a higher percentage of patients older than 50 years (61.92% versus 55.56%, P <
      0.0001). Monitored anesthesia care (MAC) (20.15%) and sedation (2.05%) were more
      common in NORA locations. The most common minor complications were postoperative
      nausea and vomiting (1.06%), inadequate pain control (1.01%), and hemodynamic
      instability (0.62%). The most common major complications were serious hemodynamic
      instability (0.10%) and upgrade of care (0.10%). There was a greater incidence of
      complications in cardiology and radiology locations. Overall mortality was higher
      in OR versus NORA (0.04% versus 0.02%, P < 0.0001). Subcategory analysis showed
      increased incidence of death in cardiology and radiology locations (0.05%).
      CONCLUSIONS: Non-OR anesthesia procedures have lower morbidity and mortality
      rates than OR procedures, contrary to some previously published studies. However,
      the increased complication rates in both the cardiology and radiology locations
      may need to be the target of future safety investigations. Providers must ensure
      proper monitoring of patients, and NORA locations need to be held to the same
      standard of care as the main operating room. Further studies need to identify at
      risk patients and procedures that may predispose patients to complications.

PMID- 25853808
TI  - Accountability: Challenges to Getting It Right.
AB  - Patient safety experts debated accountability in health care at the 2014 annual
      National Patient Safety Foundation Congress. The debate reflected the struggles
      organizations are facing with ensuring a responsible workforce committed to
      patient safety versus the need to redesign flawed systems that are error prone.
      The question, "is it the systems or the individual?" was at issue. This article
      proposes that it is the wrong question, and the failure to apply patient safety
      science in clinical practice is contributing to the ambiguity fueling the debate.
      To transform accountability from a source of confusion to a powerful tool for
      fulfilling health care's fiduciary responsibility to protect patients from harm,
      we need to reframe our approach. This article presents the science and strategies
      to create clarity that will redirect the dialogue from a debate in which
      accountability resides to one about learning for improvement when adverse events
      occur.

PMID- 25853809
TI  - European flint landraces grown in situ reveal adaptive introgression from modern
      maize.
AB  - We have investigated the role of selection in the determination of the detected
      levels of introgression from modern maize hybrid varieties into maize landraces
      still cultivated in situ in Italy. We exploited the availability of a historical
      collection of landraces undertaken before the introduction and widespread use of
      modern maize, to analyse genomic changes that have occurred in these maize
      landraces over 50 years of co-existence with hybrid varieties. We have combined a
      previously published SSR dataset (n=21) with an AFLP loci dataset (n=168) to
      provide higher resolution power and to obtain a more detailed picture. We show
      that selection pressures for adaptation have favoured new alleles introduced by
      migration from hybrids. This shows the potential for analysis of historical
      introgression even over this short period of 50 years, for an understanding of
      the evolution of the genome and for the identification of its functionally
      important regions. Moreover, this demonstrates that landraces grown in situ
      represent almost unique populations for use for such studies when the focus is on
      the domesticated plant. This is due to their adaptation, which has arisen from
      their dynamic evolution under a continuously changing agro-ecological
      environment, and their capture of new alleles from hybridisation. We have also
      identified loci for which selection has inhibited introgression from modern
      germplasm and has enhanced the distinction between landraces and modern maize.
      These loci indicate that selection acted in the past, during the formation of the
      flint and dent gene pools. In particular, the locus showing the strongest signals
      of selection is a Misfit transposable element. Finally, molecular
      characterisation of the same samples with two different molecular markers has
      allowed us to compare their performances. Although the genetic-diversity and
      population-structure analyses provide the same global qualitative pattern, which
      thus provides the same inferences, there are differences related to their natures
      and characteristics. 

PMID- 25853811
TI  - Correction: breast cancer screening in Saudi Arabia: free but almost no takers.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0119051.]. 

PMID- 25853810
TI  - Nitric oxide sustains IL-1beta expression in human dendritic cells enhancing
      their capacity to induce IL-17-producing T-cells.
AB  - The role played by lung dendritic cells (DCs) which are influenced by external
      antigens and by their redox state in controlling inflammation is unclear. We
      studied the role played by nitric oxide (NO) in DC maturation and function. Human
      DCs were stimulated with a long-acting NO donor, DPTA NONOate, prior to exposure
      to lipopolysaccharide (LPS). Dose-and time-dependent experiments were performed
      with DCs with the aim of measuring the release and gene expression of
      inflammatory cytokines capable of modifying T-cell differentiation, towardsTh1,
      Th2 and Th17 cells. NO changed the pattern of cytokine release by LPS-matured
      DCs, dependent on the concentration of NO, as well as on the timing of its
      addition to the cells during maturation. Addition of NO before LPS-induced
      maturation strongly inhibited the release of IL-12, while increasing the
      expression and release of IL-23, IL-1beta and IL-6, which are all involved in
      Th17 polarization. Indeed, DCs treated with NO efficiently induced the release of
      IL-17 by T-cells through IL-1beta. Our work highlights the important role that NO
      may play in sustaining inflammation during an infection through the preferential
      differentiation of the Th17 lineage. 

PMID- 25853812
TI  - Mucosal-associated invariant T cell is a potential marker to distinguish
      fibromyalgia syndrome from arthritis.
AB  - BACKGROUND: Fibromyalgia (FM) is defined as a widely distributed pain. While many
      rheumatologists and pain physicians have considered it to be a pain disorder,
      psychiatry, psychology, and general medicine have deemed it to be a syndrome
      (FMS) or psychosomatic disorder. The lack of concrete structural and/or
      pathological evidence has made patients suffer prejudice that FMS is a medically
      unexplained symptom, implying inauthenticity. Furthermore, FMS often exhibits
      comorbidity with rheumatoid arthritis (RA) or spondyloarthritis (SpA), both of
      which show similar indications. In this study, disease specific biomarkers were
      sought in blood samples from patients to facilitate objective diagnoses of FMS,
      and distinguish it from RA and SpA. METHODS: Peripheral blood mononuclear cells
      (PBMCs) from patients and healthy donors (HD) were subjected to multicolor flow
      cytometric analysis. The percentage of mucosal-associated invariant T (MAIT)
      cells in PBMCs and the mean fluorescent intensity (MFI) of cell surface antigen
      expression in MAIT cells were analyzed. RESULTS: There was a decrease in the MAIT
      cell population in FMS, RA, and SpA compared with HD. Among the cell surface
      antigens in MAIT cells, three chemokine receptors, CCR4, CCR7, and CXCR1, a
      natural killer (NK) receptor, NKp80, a signaling lymphocyte associated molecule
      (SLAM) family, CD150, a degrunulation marker, CD107a, and a coreceptor, CD8beta
      emerged as potential biomarkers for FMS to distinguish from HD. Additionally, a
      memory marker, CD44 and an inflammatory chemokine receptor, CXCR1 appeared
      possible markers for RA, while a homeostatic chemokine receptor, CXCR4 deserved
      for SpA to differentiate from FMS. Furthermore, the drug treatment interruption
      resulted in alternation of the expression of CCR4, CCR5, CXCR4, CD27, CD28,
      inducible costimulatory molecule (ICOS), CD127 (IL-7 receptor alpha), CD94,
      NKp80, an activation marker, CD69, an integrin family member, CD49d, and a
      dipeptidase, CD26, in FMS. CONCLUSIONS: Combined with the currently available
      diagnostic procedures and criteria, analysis of MAIT cells offers a more
      objective standard for the diagnosis of FMS, RA, and SpA, which exhibit
      multifaceted and confusingly similar clinical manifestations.

PMID- 25853814
TI  - Transgene expression and Bt protein content in transgenic Bt maize (MON810) under
      optimal and stressful environmental conditions.
AB  - Bt protein content in transgenic insect resistant (Bt) maize may vary between
      tissues within plants and between plants growing under different environmental
      conditions. However, it is unknown whether and how Bt protein content correlates
      with transgene expression, and whether this relationship is influenced by
      stressful environmental conditions. Two Bt maize varieties containing the same
      transgene cassette (MON 810) were grown under optimal and stressful conditions.
      Before and during stress exposure, the upper leaves were analysed for transgene
      expression using quantitative RT-PCR and for Bt content using ELISA. Under
      optimal conditions there was no significant difference in the transgene
      expression between the two investigated Bt maize varieties whereas Bt protein
      content differed significantly. Transgene expression was correlated with Bt
      protein content in only one of the varieties. Under stressful environmental
      conditions we found similar transgene expressions as under optimal conditions but
      Bt content responded differently. These results suggest that Bt content is not
      only controlled by the transgene expression but is also dependent on the genetic
      background of the maize variety. Under stressful conditions the concentration of
      Bt protein is even more difficult to predict. 

PMID- 25853813
TI  - Low birth weight at term and its determinants in a tertiary hospital of Nepal: a
      case-control study.
AB  - Birth weight of a child is an important indicator of its vulnerability for
      childhood illness and chances of survival. A large number of infant deaths can be
      averted by appropriate management of low birth weight babies and prevention of
      factors associated with low birth weight. The prevalence of low birth weight
      babies in Nepal is estimated to be about 12-32%.Our study aimed at identifying
      major determinants of low birth weight among term babies in Nepal. A hospital
      based retrospective case control study was conducted in maternity ward of
      Tribhuvan University Teaching Hospital from February to July 2011. A total of 155
      LBW babies and 310 controls were included in the study. Mothers admitted to
      maternity ward during the study period were interviewed, medical records were
      assessed and anthropometric measurements were done. Risk factors, broadly
      classified into proximal and distal factors, were assessed for any association
      with birth of low-birth weight babies. Regression analysis revealed that a
      history of premature delivery (adjusted odds ratio; aOR5.24, CI 1.05-26.28), hard
      physical work during pregnancy (aOR1.48, CI 0.97-2.26), younger age of mother
      (aOR1.98, CI 1.15-3.41), mothers with haemoglobin level less than 11gm/dl
      (aOR0.51, CI0.24-1.07) and lack of consumption of nutritious food during
      pregnancy (aOR1.99, CI 1.28-3.10) were significantly associated with the birth of
      LBW babies. These factors should be addressed with appropriate measures so as to
      decrease the prevalence of low birth weight among term babies in Nepal. 

PMID- 25853815
TI  - Lonafarnib is a potential inhibitor for neovascularization.
AB  - Atherosclerosis is a common cardiovascular disease that involves the build-up of
      plaque on the inner walls of the arteries. Intraplaque neovacularization has been
      shown to be essential in the pathogenesis of atherosclerosis. Previous studies
      showed that small-molecule compounds targeting farnesyl transferase have the
      ability to prevent atherosclerosis in apolipoprotein E-deficient mice, but the
      underlying mechanism remains to be elucidated. In this study, we found that
      lonafarnib, a specific inhibitor of farnesyl transferase, elicits inhibitory
      effect on vascular endothelial capillary assembly in vitro in a dose-dependent
      manner. In addition, we showed that lonafarnib treatment led to a dose-dependent
      decrease in scratch wound closure in vitro, whereas it had little effect on
      endothelial cell proliferation. These data indicate that lonafarnib inhibits
      neovascularization via directly targeting endothelial cells and disturbing their
      motility. Moreover, we demonstrated that pharmacological inhibition of farnesyl
      transferase by lonafarnib significantly impaired centrosome reorientation toward
      the leading edge of endothelial cells. Mechanistically, we found that the
      catalytic beta subunit of farnesyl transferase associated with a cytoskeletal
      protein important for the establishment and maintenance of cell polarity.
      Additionally, we showed that lonafarnib remarkably inhibited the expression of
      the cytoskeletal protein and interrupted its interaction with farnesyl
      transferase. Our findings thus offer novel mechanistic insight into the
      protective effect of farnesyl transferase inhibitors on atherosclerosis and
      provide encouraging evidence for the potential use of this group of agents in
      inhibiting plaque neovascularization. 

PMID- 25853816
TI  - Botulinum neurotoxin type A induces TLR2-mediated inflammatory responses in
      macrophages.
AB  - Botulinum neurotoxin type A (BoNT/A) is the most potent protein toxin and causes
      fatal flaccid muscle paralysis by blocking neurotransmission. Application of
      BoNT/A has been extended to the fields of therapeutics and biodefense.
      Nevertheless, the global response of host immune cells to authentic BoNT/A has
      not been reported. Employing microarray analysis, we performed global
      transcriptional profiling of RAW264.7 cells, a murine alveolar macrophage cell
      line. We identified 70 genes that were modulated following 1 nM BoNT/A treatment.
      The altered genes were mainly involved in signal transduction, immunity and
      defense, protein metabolism and modification, neuronal activities, intracellular
      protein trafficking, and muscle contraction. Microarray data were validated with
      real-time RT-PCR for seven selected genes including tlr2, tnf, inos, ccl4, slpi,
      stx11, and irg1. Proinflammatory mediators such as nitric oxide (NO) and tumor
      necrosis factor alpha (TNFalpha) were induced in a dose-dependent manner in
      BoNT/A-stimulated RAW264.7 cells. Increased expression of these factors was
      inhibited by monoclonal anti-Toll-like receptor 2 (TLR2) and inhibitors specific
      to intracellular proteins such as c-Jun N-terminal kinase (JNK), extracellular
      signal-regulated kinase (ERK), and p38 mitogen-activated protein kinase (MAPK).
      BoNT/A also suppressed lipopolysaccharide-induced NO and TNFalpha production from
      RAW264.7 macrophages at the transcription level by blocking activation of JNK,
      ERK, and p38 MAPK. As confirmed by TLR2-/- knock out experiments, these results
      suggest that BoNT/A induces global gene expression changes in host immune cells
      and that host responses to BoNT/A proceed through a TLR2-dependent pathway, which
      is modulated by JNK, ERK, and p38 MAPK. 

PMID- 25853818
TI  - Reproducibility in echocardiographic assessment of diastolic function in a
      population based study (the STANISLAS Cohort study).
AB  - INTRODUCTION: There is limited evidence regarding intra-observer and inter
      observer variations in echocardiographic measurements of diastolic function. This
      study aimed to assess this reproducibly within a population-based cohort study.
      METHODS: Sixty subjects in sinus rhythm were randomly selected among 4th visit
      participants of the STANISLAS Cohort (Lorraine region, France). This 4th
      examination systematically included M-mode, 2-dimensional, DTI and pulsed-wave
      Doppler echocardiograms. Reproducibility of variables was studied by intra-class
      correlation coefficients (ICC) and Bland Altman plots. RESULTS: Our population
      was on average middle-aged (50 +/- 14 y), overweight (BMI = 26 +/- 6 kg/m2) and
      non-smoking (87%) with a quarter of the participants having self-declared
      hypertension or treated with anti-hypertensive medication(s). Intra-observer ICC
      were > 0.90 for all analyzed parameters except for left ventricular ejection
      fraction (LVEF) which was 0.89 (0.81-0.93). The mean relative intra-observer
      differences were small and limits of agreement of relative differences were
      narrow for all considered parameters (<5% and <15% respectively). Inter-observer
      ICC were > 0.90 for all analyzed parameters except for LVEF (ICC = 0.87) and both
      mitral and pulmonary A wave duration (0.83 and 0.73 respectively). The mean
      relative inter-observer differences were <5% for all parameters except for
      pulmonary A wave duration (mean difference = 6.5%). Limits of agreement of
      relative differences were narrow (<15%), except for mitral A wave duration and
      velocity (both <20%) as well as left ventricular mass and pulmonary A wave
      duration (both <30%). Intra-observer agreements with regard to the presence and
      severity of diastolic dysfunction were excellent (Kappa = 0.93 (0.83-1.00) and
      0.88 (0.75-0.99), respectively). CONCLUSION: In this validation study within the
      STANISLAS cohort, diastolic function echocardiographic parameters were found to
      be highly reproducible. Diastolic dysfunction consequently appears as a highly
      effective clinical and research tool.

PMID- 25853817
TI  - Distinctive patterns of evolution of the delta-globin gene (HBD) in primates.
AB  - In most vertebrates, hemoglobin (Hb) is a heterotetramer composed of two
      dissimilar globin chains, which change during development according to the
      patterns of expression of alpha- and beta-globin family members. In placental
      mammals, the beta-globin cluster includes three early-expressed genes,
      epsilon(HBE)-gamma(HBG)-psibeta(HBBP1), and the late expressed genes, delta (HBD)
      and beta (HBB). While HBB encodes the major adult beta-globin chain, HBD is
      weakly expressed or totally silent. Paradoxically, in human populations HBD shows
      high levels of conservation typical of genes under strong evolutionary
      constraints, possibly due to a regulatory role in the fetal-to-adult switch
      unique of Anthropoid primates. In this study, we have performed a comprehensive
      phylogenetic and comparative analysis of the two adult beta-like globin genes in
      a set of diverse mammalian taxa, focusing on the evolution and functional
      divergence of HBD in primates. Our analysis revealed that anthropoids are an
      exception to a general pattern of concerted evolution in placental mammals,
      showing a high level of sequence conservation at HBD, less frequent and shorter
      gene conversion events. Moreover, this lineage is unique in the retention of a
      functional GATA-1 motif, known to be involved in the control of the developmental
      expression of the beta-like globin genes. We further show that not only the mode
      but also the rate of evolution of the delta-globin gene in higher primates are
      strictly associated with the fetal/adult beta-cluster developmental switch. To
      gain further insight into the possible functional constraints that have been
      shaping the evolutionary history of HBD in primates, we calculated dN/dS (omega)
      ratios under alternative models of gene evolution. Although our results indicate
      that HBD might have experienced different selective pressures throughout primate
      evolution, as shown by different omega values between apes and Old World Monkeys
      + New World Monkeys (0.06 versus 0.43, respectively), these estimates
      corroborated a constrained evolution for HBD in Anthropoid lineages, which is
      unlikely to be related to protein function. Collectively, these findings suggest
      that sequence change at the delta-globin gene has been under strong selective
      constraints over 65 Myr of primate evolution, likely due to a regulatory role in
      ontogenic switches of gene expression. 

PMID- 25853819
TI  - The GAB2 and BDNF polymorphisms and the risk for late-onset Alzheimer's disease
      in an elderly Brazilian sample.
AB  - BACKGROUND: Evidences suggest that GAB2 and BDNF genes may be associated with
      Alzheimer's disease (AD). We aimed to investigate the GAB2 rs2373115 and BDNF
      rs6265 polymorphisms and the risk of AD in a Brazilian sample. METHODS: 269 AD
      patients and 114 controls were genotyped with Real-time PCR. Multifactor
      dimensionality reduction (MDR) was employed to explore the effects of gene-gene
      interactions. RESULTS: GAB2 and BDNF were not associated with AD in our sample.
      Nevertheless BDNF Val allele (rs6265) presented a synergic association with the
      APOE epsilon4 allele. A multiple logistic regression demonstrated that the APOE
      epsilon4 allele and years of education were the best predictors for AD. In
      epsilon4 non-carriers sex, education and hypertension were independently
      correlated with AD, while in epsilon4 carriers we did not observe any
      association. The findings were further confirmed by bootstrapping method.
      CONCLUSIONS: Our data suggest that the interaction of BDNF and APOE has
      significant effect on AD. Moreover in absence of epsilon4, female sex, low level
      of education and hypertension are independently associated with AD. Interventions
      aimed to prevent AD should focus on these factors and also taking into account
      the APOE alleles.

PMID- 25853821
TI  - Simultaneous quantification of multiple urinary naphthalene metabolites by liquid
      chromatography tandem mass spectrometry.
AB  - Naphthalene is an environmental toxicant to which humans are exposed. Naphthalene
      causes dose-dependent cytotoxicity to murine airway epithelial cells but a link
      between exposure and human pulmonary disease has not been established.
      Naphthalene toxicity in rodents depends on P450 metabolism. Subsequent
      biotransformation results in urinary elimination of several conjugated
      metabolites. Glucuronide and sulfate conjugates of naphthols have been used as
      markers of naphthalene exposure but, as the current studies demonstrate, these
      assays provide a limited view of the range of metabolites generated from the
      parent hydrocarbon. Here, we present a liquid chromatography tandem mass
      spectrometry method for measurement of the glucuronide and sulfate conjugates of
      1-naphthol as well as the mercapturic acids and N-acetyl glutathione conjugates
      from naphthalene epoxide. Standard curves were linear over 2 log orders. On
      column detection limits varied from 0.91 to 3.4 ng; limits of quantitation from
      1.8 to 6.4 ng. The accuracy of measurement of spiked urine standards was -13.1 to
      + 5.2% of target and intra-day and inter-day variability averaged 7.2 (+/- 4.5)
      and 6.8 (+/- 5.0) %, respectively. Application of the method to urine collected
      from mice exposed to naphthalene at 15 ppm (4 hrs) showed that glutathione
      derived metabolites accounted for 60-70% of the total measured metabolites and
      sulfate and glucuronide conjugates were eliminated in equal amounts. The method
      is robust and directly measures several major naphthalene metabolites including
      those derived from glutathione conjugation of naphthalene epoxide. The assays do
      not require enzymatic deconjugation, extraction or derivatization thus
      simplifying sample work up. 

PMID- 25853820
TI  - When is exposure to a natural disaster traumatic? Comparison of a trauma
      questionnaire and disaster exposure inventory.
AB  - Few studies have compared the sensitivity of trauma questionnaires to disaster
      inventories for assessing the prevalence of exposure to natural disaster or
      associated risk for post-disaster psychopathology. The objective of this analysis
      was to compare reporting of disaster exposure on a trauma questionnaire (Brief
      Trauma Questionnaire [BTQ]) to an inventory of disaster experience. Between 2011
      and 2014, a sample of 841 reproductive-aged southern Louisiana women were
      interviewed using the BTQ and completed a detailed inventory about exposure to
      hurricanes and flooding. Post-traumatic stress disorder (PTSD) symptomology was
      measured with the Post-Traumatic Stress Checklist, and depression with the
      Edinburgh Depression Scale. The single question addressing disaster exposure on
      the BTQ had a sensitivity of between 65% and 70% relative to the more detailed
      questions. Reporting disaster exposure on the BTQ was more likely for those who
      reported illness/injury due to a hurricane or flood (74%-77%) or danger (77-79%),
      compared to those who reported damage (69-71%) or evacuation (64-68%). Reporting
      disaster exposure on the BTQ was associated with depression (odds ratio [OR]
      2.29, 95% confidence interval [CI] 1.43-3.68). A single question is unlikely to
      be useful for assessing the degree of exposure to disaster across a broad
      population, and varies in utility depending on the mental health outcome of
      interest: the single trauma question is useful for assessing depression risk. 

PMID- 25853822
TI  - Unscheduled-return-visits after an emergency department (ED) attendance and
      clinical link between both visits in patients aged 75 years and over: a
      prospective observational study.
AB  - BACKGROUND: Predictors of unscheduled return visits (URV), best time-frame to
      evaluate URV rate and clinical relationship between both visits have not yet been
      determined for the elderly following an ED visit. METHODS: We conducted a
      prospective-observational study including 11,521 patients aged >=75-years and
      discharged from ED (5,368 patients (53.5%)) or hospitalized after ED visit (6,153
      patients). Logistic Regression and time-to-failure analyses including Cox
      proportional model were performed. RESULTS: Mean time to URV was 17 days; 72
      hour, 30-day and 90-day URV rates were 1.8%, 6.1% and 10% respectively.
      Multivariate analysis indicates that care-pathway and final disposition decisions
      were significantly associated with a 30-day URV. Thus, we evaluated predictors of
      30-day URV rates among non-admitted and hospitalized patient groups. By using the
      Cox model we found that, for non-admitted patients, triage acuity and diagnostic
      category and, for hospitalized patients, that visit time (day, night) and
      diagnostic categories were significant predictors (p<0.001). For URV, we found
      that 25% were due to closely related-clinical conditions. Time lapses between
      both visits constituted the strongest predictor of closely related-clinical
      conditions. CONCLUSION: Our study shows that a decision of non-admission in
      emergency departments is linked with an accrued risk of URV, and that some
      diagnostic categories are also related for non-admitted and hospitalized subjects
      alike. Our study also demonstrates that the best time frame to evaluate the URV
      rate after an ED visit is 30 days, because this is the time period during which
      most URVs and cases with close clinical relationships between two visits are
      concentrated. Our results suggest that URV can be used as an indicator or
      quality.

PMID- 25853824
TI  - Correction: Bacterial immune evasion through manipulation of host inhibitory
      immune signaling.
AB  - [This corrects the article DOI: 10.1371/journal.ppat.1004644.]. 

PMID- 25853823
TI  - Evidence for distinct coastal and offshore communities of bottlenose dolphins in
      the north east Atlantic.
AB  - Bottlenose dolphin stock structure in the northeast Atlantic remains poorly
      understood. However, fine scale photo-id data have shown that populations can
      comprise multiple overlapping social communities. These social communities form
      structural elements of bottlenose dolphin (Tursiops truncatus) [corrected]
      populations, reflecting specific ecological and behavioural adaptations to local
      habitats. We investigated the social structure of bottlenose dolphins in the
      waters of northwest Ireland and present evidence for distinct inshore and
      offshore social communities. Individuals of the inshore community had a coastal
      distribution restricted to waters within 3 km from shore. These animals exhibited
      a cohesive, fission-fusion social organisation, with repeated resightings within
      the research area, within a larger coastal home range. The offshore community
      comprised one or more distinct groups, found significantly further offshore (>4
      km) than the inshore animals. In addition, dorsal fin scarring patterns differed
      significantly between inshore and offshore communities with individuals of the
      offshore community having more distinctly marked dorsal fins. Specifically,
      almost half of the individuals in the offshore community (48%) had characteristic
      stereotyped damage to the tip of the dorsal fin, rarely recorded in the inshore
      community (7%). We propose that this characteristic is likely due to interactions
      with pelagic fisheries. Social segregation and scarring differences found here
      indicate that the distinct communities are likely to be spatially and
      behaviourally segregated. Together with recent genetic evidence of distinct
      offshore and coastal population structures, this provides evidence for bottlenose
      dolphin inshore/offshore community differentiation in the northeast Atlantic. We
      recommend that social communities should be considered as fundamental units for
      the management and conservation of bottlenose dolphins and their habitat
      specialisations.

PMID- 25853826
TI  - [The medication cycle: its impact on access to and adequate use of drugs].

PMID- 25853825
TI  - Dolphins adjust species-specific frequency parameters to compensate for
      increasing background noise.
AB  - An increase in ocean noise levels could interfere with acoustic communication of
      marine mammals. In this study we explored the effects of anthropogenic and
      natural noise on the acoustic properties of a dolphin communication signal, the
      whistle. A towed array with four elements was used to record environmental
      background noise and whistles of short-beaked common-, Atlantic spotted- and
      striped-dolphins in the Canaries archipelago. Four frequency parameters were
      measured from each whistle, while Sound Pressure Levels (SPL) of the background
      noise were measured at the central frequencies of seven one-third octave bands,
      from 5 to 20 kHz. Results show that dolphins increase the whistles' frequency
      parameters with lower variability in the presence of anthropogenic noise, and
      increase the end frequency of their whistles when confronted with increasing
      natural noise. This study provides the first evidence that the synergy among SPLs
      has a role in shaping the whistles' structure of these three species, with
      respect to both natural and anthropogenic noise. 

PMID- 25853827
TI  - [Essential medicines and the TRIPS Agreement: collision between the right to
      health and intellectual property rights].
AB  - The strengthening of pharmaceutical patent protection globally puts strains on
      access to essential medicines. According to the present paper, this process has
      led to the collision of the intellectual property rights adopted in the World
      Trade Organization (WTO) Trade-Related Aspects of Intellectual Property Rights
      (TRIPS) Agreement and the right to health stated in the International Covenant on
      Economic, Social and Cultural Rights (ICESCR). Several controversies disputed in
      the WTO illustrate the confrontation between countries with a powerful
      pharmaceutical industry and the interests of developing countries. It is
      concluded that the TRIPS-plus rules subscribed to by developing countries in free
      trade agreements which give the pharmaceutical patent holder more rights than
      those stipulated in the original TRIPS Agreement are incompatible with the
      obligations to provide access to essential medicines under the right to health of
      the ICESCR. 

PMID- 25853828
TI  - [Alternatives to the drug research and development model].
AB  - One-third of the global population lacks access to medications; the situation is
      worse in poor countries, where up to 50% of the population lacks access. The
      failure of current incentive systems based in intellectual property to offer the
      necessary pharmaceutical products, especially in the global south, is a call to
      action. Problems related to drug access cannot be solved solely through
      improvements or modifications in the existing incentive models. The intellectual
      property system model does not offer sufficient innovation for developing
      countries; new mechanisms that effectively promote innovation and drug access
      simultaneously are needed. A binding international agreement on research and
      development, negotiated under the auspices of the World Health Organization,
      could provide an adequate framework for guaranteeing priority-setting,
      coordination, and sustainable financing of drugs at reasonable prices for
      developing countries. 

PMID- 25853829
TI  - [Drug prices: how they are established and existing price control systems].
AB  - Price is one of the main barriers of access to medicines. It is therefore
      important to understand how prices are formed and what factors determine the
      amount, as well as what interventions and regulations are the most appropriate
      considering their effects on access, innovation, local production and other
      potential objectives of drug policy. Economic analysis has developed a set of
      market models that can explain the behavior of prices, although actual markets
      diverge substantially from the theoretical models. Price regulation is justified
      by the so-called "market failures." Price regulation based on the cost of
      production, the most traditional form of price control, has fallen into disuse in
      favor of systems of international reference pricing and value-based pricing. 

PMID- 25853830
TI  - [Universal ethical principles and their application in clinical drug trials].
AB  - Since 1931, and especially since the Nuremberg Code of 1947, an increasing number
      of declarations, regulations, norms, guidelines, laws, resolutions, and rules
      intended to create conditions for better protection of subjects participating in
      research studies have been published, although some have meant setbacks in the
      human rights of vulnerable populations. As such, violations of the dignity of
      experimental subjects in clinical trials continue. What researchers investigate
      and how the research is done, the quality and transparency of the data, and the
      analysis and the publication of results (of both raw and processed data) respond
      to the financial interests of the pharmaceutical companies, coming into permanent
      tension with bioethical principles and the needs of society. The active
      participation of civil society is necessary to make it so that pharmaceutical
      research, results and applications subordinate economic benefits to the
      protection of human rights. 

PMID- 25853831
TI  - [The impact of researchers loyal to Big Pharma on the ethics and quality of
      clinical trials in Latin America].
AB  - This article explains the difficulties innovative pharmaceutical firms have in
      repaying shareholders with attractive dividends. The problem is the result of the
      expiration of the patents of blockbuster drugs and the difficulties that the
      firms have in bringing new blockbuster drugs to the market. One of the solutions
      companies have found has been to accelerate the implementation of clinical trials
      in order to expedite the commercialization of new drugs. Doing so increases the
      period in which they can sell drugs at monopoly prices. We therefore discuss how
      innovative pharmaceutical firms shorten the implementation time of clinical
      trials in Latin America and the consequences such actions have on the quality of
      the collected data, the protection of human rights of the subjects of
      experimentation, and compliance with the ethical principles approved in
      international declarations. 

PMID- 25853832
TI  - [Bioethical problems in researching new vaccines: do they respond to public
      health reasons?].
AB  - The ethical problems in vaccine research have grown in frequency and magnitude in
      last decades, due to the dominant place of the pharmaceutical industry in the
      development of such studies. Traditional issues of security and efficacy have
      been aggravated by the conflicts of interests introduced by commercial
      competition in a global market worth billions of dollars. We present here a few
      examples in which the professional integrity of researchers, the moral
      responsibility of sponsors, and the public regulation and control by national
      States are put into question. The consequences of these changes represent serious
      threats to the rights of people included in these studies as well as disputable
      progress for public health. 

PMID- 25853833
TI  - [The use of placebos in phase III clinical trials in Brazil].
AB  - In 2008, Brazil's Federal Council of Medicine [Conselho Federal de Medicina]
      (CFM)--regulatory and supervisory agency on the ethical practice of medicine-
      banned the participation of Brazilian doctors in studies using placebos for
      diseases with efficient and effective treatment. This position differs with the
      Helsinki Declaration, which allows the use of placebos in methodologically
      justified conditions. To ascertain whether the CMF's ethical regulation modified
      the use of placebos in phase III clinical trials in Brazil, characteristics of
      the records in ClinicalTrials.gov were researched in the periods from 2003 to
      2007 and from 2009 to 2013. The conclusions reached were: a) the regulations
      issued by the CFM in 2008 were ineffective and the position adopted by the
      Helsinki Declaration prevails; b) there was significant sponsorship by the
      multinational pharmaceutical industry of trials with placebos; c) the research
      was predominantly on new drugs for chronic diseases, with little study done of
      the neglected diseases which are of great importance to Brazil.

PMID- 25853834
TI  - [Antipsychotics for schizophrenia: the paradigm of psychiatric drugs].
AB  - Antipsychotic drugs do not appear to reverse the causes of schizophrenia, and
      although they can relieve symptoms in the short to medium term, in the long term
      they may not be beneficial and could even be counterproductive. Their use should
      be limited to acute situations in which agitation and tension is disabling. The
      drugs have significant adverse effects, and given the refusal of a person to
      continue taking them, a harm reduction strategy to support and monitor the
      withdrawal may be preferable to coercion. There are alternatives to neuroleptics.
      Prescribers should be more vigilant and consider the assessments of users
      regarding the drugs' effects. Adherence to treatment guidelines is low, probably
      because the guidelines are based on clinical trials of deficient quality which
      consequently should be improved and extended over a greater period of time. The
      root of the problem is likely the tautology on the etiology and biological nature
      of what is known as schizophrenia, which in fact does not seem to be more than a
      commercial and ideological construct. 

PMID- 25853835
TI  - Fear of negative evaluation biases social evaluation inference: evidence from a
      probabilistic learning task.
AB  - BACKGROUND: Fear of negative evaluation (FNE) defines social anxiety yet the
      process of inferring social evaluation, and its potential role in maintaining
      social anxiety, is poorly understood. We developed an instrumental learning task
      to model social evaluation learning, predicting that FNE would specifically bias
      learning about the self but not others. METHODS: During six test blocks (3 self
      referential, 3 other-referential), participants (n = 100) met six personas and
      selected a word from a positive/negative pair to finish their social evaluation
      sentences "I think [you are / George is]...". Feedback contingencies corresponded
      to 3 rules, liked, neutral and disliked, with P[positive word correct] = 0.8, 0.5
      and 0.2, respectively. RESULTS: As FNE increased participants selected fewer
      positive words (beta = -0.4, 95% CI -0.7, -0.2, p = 0.001), which was strongest
      in the self-referential condition (FNE * condition 0.28, 95% CI 0.01, 0.54, p =
      0.04), and the neutral and dislike rules (FNE * condition * rule, p = 0.07). At
      low FNE the proportion of positive words selected for self-neutral and self
      disliked greatly exceeded the feedback contingency, indicating poor learning,
      which improved as FNE increased. CONCLUSIONS: FNE is associated with differences
      in processing social-evaluative information specifically about the self. At low
      FNE this manifests as insensitivity to learning negative self-referential
      evaluation. High FNE individuals are equally sensitive to learning positive or
      negative evaluation, which although objectively more accurate, may have
      detrimental effects on mental health.

PMID- 25853837
TI  - The economy of motion of the totally robotic gastric bypass: technique, learning
      curve, and outcomes of a fellowship-trained, robotic bariatric surgeon.
AB  - We present our technique for a totally robot-assisted laparoscopic Roux-en-Y
      gastric bypass. Moreover, data are presented in relation to a single-surgeon
      experience with use of the robotic platform in bariatric surgery. We reviewed a
      single surgeon's console and room time from 2009 to 2013 for all robot-assisted
      Roux-en-Y gastric bypasses (RARYGBs). Revision operations were excluded. There
      were in total 168 robotic bariatric operations in this time frame. The number of
      cases performed each year and the cumulative number of each operation were
      considered as well. The change in console time as related to the number of cases
      and the change in room time as related to the console time and number of cases
      were investigated. Complications during this time and their frequency were noted
      and described. The console time for RARYGB ranged from 131 +/- 46 minutes in 2010
      to 94 +/- 29 minutes in 2013 (P<.05). There were in total 22 complications, for
      an overall complication rate of 13.1%: four anastomotic strictures (2.4%), seven
      marginal ulcerations (4.2%), two gastrointestinal bleeds (1.2%), five internal
      hernias (3.0%), two abdominal pains requiring diagnostic laparoscopy (1.2%), and
      two gastrointestinal leaks (1.2%). There were no deaths. In this series, the
      console surgeon performed 168 RARYGBs and had a leak rate of 1.2% and a mortality
      of 0% within the first 66 cases and a 0% leak rate over the next 102 cases. Thus,
      we believe that the robot has a decreased caseload requirement to reach
      proficiency with comparable outcomes versus both the hybrid and purely
      laparoscopic approaches.

PMID- 25853838
TI  - Self-assembly fabrication of hollow mesoporous silica@Co-Al layered double
      hydroxide@graphene and application in toxic effluents elimination.
AB  - Here, we propose a self-assembly process to prepare hierarchical HM-SiO2@Co-Al
      LDH@graphene, with the purpose of combining their outstanding performance. Hollow
      mesoporous silica was first synthesized as the core, using a novel sonochemical
      method, followed by a controlled shell coating process and chemical reduction. As
      a result of the electrostatic potential difference among HM-SiO2, Co-Al LDH, and
      graphene oxide, the HM-SiO2 spheres were coated by Co-Al LDH and graphene.
      Subsequently, the HM-SiO2@Co-Al LDH@graphene spheres were introduced into an
      epoxy resin (EP) matrix for investigation of their toxic effluents capture and
      elimination effectiveness during combustion. The amount of toxic CO and volatile
      organic compounds from the epoxy resin decomposition significantly suppressed
      after incorporating the HM-SiO2@Co-Al LDH@graphene hybrids, implying a reduced
      toxicity. 

PMID- 25853836
TI  - Antiplatelet therapy discontinuation and the risk of serious cardiovascular
      events after coronary stenting: observations from the CREDO-Kyoto Registry Cohort
      2.
AB  - Relation of antiplatelet therapy (APT) discontinuation with the risk of serious
      cardiovascular events has not been fully addressed yet. This study is aimed to
      evaluate the risk of ischemic event after APT discontinuation based on long-term
      APT status of large cohort. In the CREDO-Kyoto Registry Cohort-2 enrolling 15939
      consecutive patients undergoing first coronary revascularization, 10470 patients
      underwent percutaneous coronary intervention either with bare-metal stents (BMS)
      only (N=5392) or sirolimus-eluting stents (SES) only (N=5078). Proportions of
      patients taking dual-APT were 67.3% versus 33.4% at 1-year, and 48.7% versus
      24.3% at 5-year in the SES and BMS strata, respectively. We evaluated daily APT
      status (dual-, single- and no-APT) and linked the adverse events to the APT
      status just 1-day before the events. No-APT as compared with dual- or single-APT
      was associated with significantly higher risk for stent thrombosis (ST) beyond 1
      month after SES implantation (cumulative incidence rates beyond 1-month: 1.23
      versus 0.15/0.29, P<0.001/P<0.001), while higher risk of no-APT for ST was
      evident only until 6-month after BMS implantation (incidence rates between 1- and
      6-month: 8.43 versus 0.71/1.20, P<0.001/P<0.001, and cumulative incidence rates
      beyond 6-month: 0.31 versus 0.11/0.08, P=0.16/P=0.08). No-APT as compared with
      dual- or single-APT was also associated with significantly higher risk for
      spontaneous myocardial infarction (MI) and stroke regardless of the types of
      stents implanted. Single-APT as compared with dual-APT was not associated with
      higher risk for serious adverse events, except for the marginally higher risk for
      ST in the SES stratum. In conclusion, discontinuation of both aspirin and
      thienopyridines was associated with increased risk for serious cardiovascular
      events including ST, spontaneous MI and stroke beyond 1-month after coronary
      stenting. 

PMID- 25853839
TI  - Correction to "Initial Events in the Degradation of Hyaluronan Catalyzed by
      Hyaluronate Lyase from Streptococcus pneumoniae: QM/MM Simulation".

PMID- 25853840
TI  - Engineering Escherichia coli into a protein delivery system for mammalian cells.
AB  - Many Gram-negative pathogens encode type 3 secretion systems, sophisticated
      nanomachines that deliver proteins directly into the cytoplasm of mammalian
      cells. These systems present attractive opportunities for therapeutic protein
      delivery applications; however, their utility has been limited by their inherent
      pathogenicity. Here, we report the reengineering of a laboratory strain of
      Escherichia coli with a tunable type 3 secretion system that can efficiently
      deliver heterologous proteins into mammalian cells, thereby circumventing the
      need for virulence attenuation. We first introduced a 31 kB region of Shigella
      flexneri DNA that encodes all of the information needed to form the secretion
      nanomachine onto a plasmid that can be directly propagated within E. coli or
      integrated into the E. coli chromosome. To provide flexible control over type 3
      secretion and protein delivery, we generated plasmids expressing master
      regulators of the type 3 system from either constitutive or inducible promoters.
      We then constructed a Gateway-compatible plasmid library of type 3 secretion
      sequences to enable rapid screening and identification of sequences that do not
      perturb function when fused to heterologous protein substrates and optimized
      their delivery into mammalian cells. Combining these elements, we found that
      coordinated expression of the type 3 secretion system and modified target protein
      substrates produces a nonpathogenic strain that expresses, secretes, and delivers
      heterologous proteins into mammalian cells. This reengineered system thus
      provides a highly flexible protein delivery platform with potential for future
      therapeutic applications. 

PMID- 25853842
TI  - Preduodenal superior mesenteric vein and Whipple procedure with vascular
      reconstruction-A case report.
AB  - INTRODUCTION: Portal vein (PV) disorders are various, but rare. Here, we report a
      preduodenal superior mesenteric vein (PDSMV) in a patient who underwent a
      pancreaticoduodenectomy. PRESENTATION OF CASE: A 67-year old woman with familial
      adenomatosis polyposis was suspicious for cancer of the papilla of vater and
      scheduled for surgery. Pre-operative diagnostic revealed a PDSMV continuing into
      the left PV. The splenic vein (SV) continued directly into the right PV without
      forming ananatomic PV confluence. Eight centimetre of the PDSMV were resected
      during the pancreaticoduodenectomy and reconnected using a
      polytetrafluoroethylene prosthesis. On day 1, early graft thrombosis was treated
      by thrombectomy and change to a larger graft. Pathology confirmed a R0-resection
      of the adenocarcinoma of the papilla of vater (pTis pN0,G2). At three-month
      follow-up, the patient was cancer-free and clinically asymptomatic, although, a
      late graft thrombosis with accompanying newly build venous collaterals passing
      mesenteric blood to the SV were found. DISCUSSION: Rare PV disorders like a PDSMV
      do not contradict pancreatic surgery, but should be treated in experienced
      centres. Skills of SMV/PV reconstruction and its peri-operative management might
      be beneficial for successful outcome. Despite late graft thrombosis no clinical
      disadvantage occurred most likely due to preservation of the SV and of potential
      venous collateral pathways. CONCLUSION: Extended surgical procedures like a
      pancreaticoduodenectomy are realisable in patients with PV disorders, but require
      awareness, adequate radiological interpretation and specific surgical experience
      for secure treatment.

PMID- 25853841
TI  - Cardio-ankle vascular index is associated with cardiovascular target organ damage
      and vascular structure and function in patients with diabetes or metabolic
      syndrome, LOD-DIABETES study: a case series report.
AB  - BACKGROUND: The cardio ankle vascular index (CAVI) is a new index of the overall
      stiffness of the artery from the origin of the aorta to the ankle. This index can
      estimate the risk of atherosclerosis. We aimed to find the relationship between
      CAVI and target organ damage (TOD), vascular structure and function, and
      cardiovascular risk factors in Caucasian patients with type 2 diabetes mellitus
      or metabolic syndrome. METHODS: We included 110 subjects from the LOD-Diabetes
      study, whose mean age was 61 +/- 11 years, and 37.3% were women. Measurements of
      CAVI, brachial ankle pulse wave velocity (ba-PWV), and ankle brachial index (ABI)
      were taken using the VaSera device. Cardiovascular risk factors, renal function
      by creatinine, glomerular filtration rate, and albumin creatinine index were also
      obtained, as well as cardiac TOD with ECG and vascular TOD and carotid intima
      media thickness (IMT), carotid femoral PWV (cf-PWV), and the central and
      peripheral augmentation index (CAIx and PAIx). The Framingham-D'Agostino scale
      was used to measure cardiovascular risk. RESULTS: Mean CAVI was 8.7 +/- 1.3. More
      than half (54%) of the participants showed one or more TOD (10% cardiac, 13%
      renal; 48% vascular), and 13% had ba-PWV >= 17.5 m/s. Patients with any TOD had
      the highest CAVI values: 1.15 (CI 95% 0.70 to 1.61, p < 0.001) and 1.14 (CI 95%
      0.68 to 1.60, p < 0.001) when vascular TOD was presented, and 1.30 (CI 95% 0.51
      to 2.10, p = 0.002) for the cardiac TOD. The CAVI values had a positive
      correlation with HbA1c and systolic and diastolic blood pressure, and a negative
      correlation with waist circumference and body mass index. The positive
      correlations of CAVI with IMT (beta = 0.29; p < 0.01), cf-PWV (beta = 0.83; p <
      0.01), ba-PWV (beta = 2.12; p < 0.01), CAIx (beta = 3.42; p < 0.01), and PAIx
      (beta = 5.05; p = 0.04) remained after adjustment for cardiovascular risk, body
      mass index, and antihypertensive, lipid-lowering, and antidiabetic drugs.
      CONCLUSIONS: The results of this study suggest that the CAVI is positively
      associated with IMT, cf-PWV, ba-PWV, CAIx, and PAIx, regardless of cardiovascular
      risk and the drug treatment used. Patients with cardiovascular TOD have higher
      values of CAVI. TRIAL REGISTRATION: Clinical Trials.gov Identifier: NCT01065155.

PMID- 25853843
TI  - Tailgut cyst: A case report and literature review.
AB  - INTRODUCTION: Tailgut cysts are rare diseases but can be challenging to manage.
      PRESENTATION OF CASE: This is a case report of a tailgut cyst, in a 42 year old
      female. The cyst was incidentally detected on imaging, and treated with Kraske
      surgical approach. DISCUSSION: Hereby, we review the relevant information present
      in the medical literature about the incidence, methods of diagnosis, treatment
      options and management plans. CONCLUSION: Surgical management should be tailored
      individually for each patient, based on the advantages and disadvantages of each
      surgical approach.

PMID- 25853844
TI  - Obscure gastrointestinal bleeding due to multifocal intestinal angiosarcoma.
AB  - INTRODUCTION: Intestinal angiosarcomas are an extremely rare and aggressive
      vascular tumors, with a few cases reported in the literature. PRESENTATION OF
      CASE: A 45 years-old male arrived to our hospital with intermittent
      gastrointestinal bleeding presenting melena and weight loss, he has antecedent of
      pelvic radiotherapy ten years before admission for an unknown pelvic tumor.
      Emergency surgery was required because of uncontrolled bleeding and hemodynamic
      instability. Histopathological findings revealed a multifocal high-grade
      epithelioid angiosarcoma, with cells reactive for CD31, keratins CKAE 1/AE3 and
      factor VIII. DISCUSSION: Angiosarcomas are aggressive tumors with a high rate of
      lymph node metastasis and peripheral organs. The diagnosis is difficult because
      it present nonspecific clinical presentation, radiological and histopathological
      findings. There are few reports of angiosarcoma involving the small intestine and
      the most common presentation are abdominal pain and gastrointestinal bleeding.
      There is not enough information for intestinal angiosarcoma secondary to
      radiation therapy, but there have been proposed criteria for diagnosis: no
      microscopic or clinical evidence of antecedent malignant lesion, angiosarcoma
      presented in the field of irradiation, long latency period between radiation and
      angiosarcoma and histological confirmation. We suspect our patient course with a
      secondary form of angiosarcoma. Therapy for bleeding angiosarcoma consists in
      control of bleeding and medical management to stabilize the patient. Once
      accomplished surgical resection is required. CONCLUSION: We should keep in mind
      this tumors as a cause of obscure intestinal bleeding in patients with medical
      history of radiation therapy.

PMID- 25853845
TI  - Transoral surgery for oropharyngeal tumors using the Medrobotics((r)) Flex((r))
      System - a case report.
AB  - INTRODUCTION: Transoral resection of pharyngeal tumors with acceptable
      oncological and functional results can be challenging due to their location in a
      narrow anatomic space. CASE PRESENTATION: In this case report, we demonstrate
      successful visualization and resection of a squamous cell carcinoma of the
      oropharynx using the novel Medrobotics((r)) Flex((r)) System. The
      Medrobotics((r)) Flex((r)) System (Medrobotics Corp., Raynham, MA, USA) is an
      operator controlled flexible endoscope system that includes a rigid endoscope and
      computer-assisted controllers, with two external channels for the use of
      compatible, 3.5mm flexible instruments. DISCUSSION: In a 74-year old female
      patient a T1 squamous cell carcinoma of the oropharynx was visualized and
      completely resected using this system. The Medrobotics((r)) Flex((r)) System is a
      promising device for transoral approaches in resection of tumors within the
      pharynx. CONCLUSION: Good visualization, access, and flexibility of the endoscope
      and instruments are hereby clear advantages of the system compared to commonly
      used systems.

PMID- 25853846
TI  - A facile solvothermal growth of single crystal mixed halide perovskite
      CH3NH3Pb(Br(1-x)Cl(x))3.
AB  - We demonstrate a facile synthetic approach for preparing mixed halide perovskite
      (CH3NH3)Pb(Br1-xClx)3 single crystals by the solvothermal growth of
      stoichiometric PbBr2 and [(1 - y)CH3NH3Br + yCH3NH3Cl] DMF precursor solutions.
      The band gap of (CH3NH3)Pb(Br1-xClx)3 single crystals increased and the unit cell
      dimensions decreased with an increase in Cl content x, consistent with previous
      theoretical predictions. Interestingly, the Cl/Br ratio in the (CH3NH3)Pb(Br1
      xClx)3 single crystals is larger than that of the precursor solution, suggesting
      an unusual crystal growth mechanism. 

PMID- 25853848
TI  - Association of APC, GSTP1 and SOCS1 promoter methylation with the risk of
      hepatocellular carcinoma: a meta-analysis.
AB  - Studies of the relationships of adenomatous polyposis coli (APC), glutathione-S
      transferase P1 (GSTP1) and suppressor of the cytokine signalling 1 (SOCS1)
      promoter region methylation with the risk of hepatocellular carcinoma (HCC) have
      yielded inconsistent results. We carried out the current meta-analysis to
      comprehensively assess the associations between APC, GSTP1 and SOCS1 promoter
      methylation frequency and the risk of HCC. All relevant reports were identified
      by searching the PubMed, Embase, Web of Science, CNKI and the Chinese BioMedical
      Literature databases before 1 March 2014, with restriction to articles published
      in the Chinese and English languages. Pooled odds ratios (ORs) and corresponding
      95% confidence intervals (CIs) were calculated to investigate the rates of APC,
      GSTP1 and SOCS1 promoter methylation and the risk of HCC. Our meta-analysis
      identified relationships of APC (12 studies with 592 HCC tumour tissues), GSTP1
      (14 studies including 646 HCC tumour tissues) and SOCS1 (11 studies with 512 HCC
      tumour tissues) promoter methylation with the risk of HCC. Compared with
      paracancerous tissues, the pooled ORs of APC, GSTP1 and SOCS1 promoter region
      methylation in HCC cancer tissues were 5.32 (95% CI=2.96-9.56), 5.65, (95%
      CI=3.41-9.35) and 2.73 (95% CI=1.37-5.44), respectively. Compared with normal
      liver tissues as controls, the pooled ORs of APC, GSTP1 and SOCS1 promoter region
      methylation in HCC cancer tissues were 20.43 (95% CI=5.56-75.08), 18.78 (95%
      CI=5.76-61.19) and 13.00 (95% CI=5.20-32.47), respectively. Subgroup analysis by
      ethnicity showed that APC, GSTP1 and SOCS1 promoter methylation was associated
      significantly with the risk of HCC in both Asian and White populations (all
      P<0.05). Our meta-analysis suggested strong associations between APC, GSTP1 and
      SOCS1 gene promoter methylation and the risk of HCC, suggesting these to be
      promising biomarkers for HCC. 

PMID- 25853847
TI  - Crotoxin from Crotalus durissus terrificus is able to down-modulate the acute
      intestinal inflammation in mice.
AB  - Inflammatory bowel diseases (IBD) is the result of dysregulation of mucosal
      innate and adaptive immune responses. Factors such as genetic, microbial and
      environmental are involved in the development of these disorders. Accordingly,
      animal models that mimic human diseases are tools for the understanding the
      immunological processes of the IBD as well as to evaluate new therapeutic
      strategies. Crotoxin (CTX) is the main component of Crotalus durissus terrificus
      snake venom and has an immunomodulatory effect. Thus, we aimed to evaluate the
      modulatory effect of CTX in a murine model of colitis induced by 2,4,6-
      trinitrobenzene sulfonic acid (TNBS). The CTX was administered intraperitoneally
      18 hours after the TNBS intrarectal instillation in BALB/c mice. The CTX
      administration resulted in decreased weight loss, disease activity index (DAI),
      macroscopic tissue damage, histopathological score and myeloperoxidase (MPO)
      activity analyzed after 4 days of acute TNBS colitis. Furthermore, the levels of
      TNF-alpha, IL-1beta and IL-6 were lower in colon tissue homogenates of TNBS-mice
      that received the CTX when compared with untreated TNBS mice. The analysis of
      distinct cell populations obtained from the intestinal lamina propria showed that
      CTX reduced the number of group 3 innate lymphoid cells (ILC3) and Th17
      population; CTX decreased IL-17 secretion but did not alter the frequency of
      CD4+Tbet+ T cells induced by TNBS instillation in mice. In contrast, increased
      CD4+FoxP3+ cell population as well as secretion of TGF-beta, prostaglandin E2
      (PGE2) and lipoxin A4 (LXA4) was observed in TNBS-colitis mice treated with CTX
      compared with untreated TNBS-colitis mice. In conclusion, the CTX is able to
      modulate the intestinal acute inflammatory response induced by TNBS, resulting in
      the improvement of clinical status of the mice. This effect of CTX is complex and
      involves the suppression of the pro-inflammatory environment elicited by
      intrarectal instillation of TNBS due to the induction of a local anti
      inflammatory profile in mice. 

PMID- 25853850
TI  - High-resolution genomic analysis: the tumor-immune interface comes into focus.
AB  - A genomic analysis of heterogeneous colorectal tumor samples has uncovered
      interactions between immunophenotype and various aspects of tumor biology, with
      implications for informing the choice of immunotherapies for specific patients
      and guiding the design of personalized neoantigen-based vaccines. 

PMID- 25853849
TI  - SaeRS-dependent inhibition of biofilm formation in Staphylococcus aureus Newman.
AB  - The SaeRS two-component regulatory system of Staphylococcus aureus is known to
      affect the expression of many genes. The SaeS protein is the histidine kinase
      responsible for phosphorylation of the response regulator SaeR. In S. aureus
      Newman, the sae system is constitutively expressed due to a point mutation in
      saeS, relative to other S. aureus strains, which results in substitution of
      proline for leucine at amino acid 18. Strain Newman is unable to form a robust
      biofilm and we report here that the biofilm-deficient phenotype is due to the
      saeSP allele. Replacement of the Newman saeSP with saeSL, or deletion of saeRS,
      resulted in a biofilm-proficient phenotype. Newman culture supernatants were
      observed to inhibit biofilm formation by other S. aureus strains, but did not
      affect biofilm formation by S. epidermidis. Culture supernatants of Newman saeSL
      or Newman DeltasaeRS had no significant effect on biofilm formation. The
      inhibitory factor was inactivated by incubation with proteinase K, but survived
      heating, indicating that the inhibitory protein is heat-stable. The inhibitory
      protein was found to affect the attachment step in biofilm formation, but had no
      effect on preformed biofilms. Replacement of saeSL with saeSP in the biofilm
      proficient S. aureus USA300 FPR3757 resulted in the loss of biofilm formation.
      Culture supernatants of USA300 FPR3757 saeSP, did not inhibit biofilm formation
      by other staphylococci, suggesting that the inhibitory factor is produced but not
      secreted in the mutant strain. A number of biochemical methods were utilized to
      isolate the inhibitory protein. Although a number of candidate proteins were
      identified, none were found to be the actual inhibitor. In an effort to reduce
      the number of potential inhibitory genes, RNA-Seq analyses were done with wild
      type strain Newman and the saeSL and DeltasaeRS mutants. RNA-Seq results
      indicated that sae regulates many genes that may affect biofilm formation by
      Newman. 

PMID- 25853851
TI  - Tether-directed bisfunctionalization reactions of c60 and c70.
AB  - Four easily isolable regio- and stereoselective bis-adducts of C60 and C70 , as
      well as a new C70 -dumbbell derivative, have been synthesized by using two
      different bismalonate tethered moieties. The derivatives that possess relatively
      long-tethered moieties show highly symmetric addition patterns, as evidenced by
      spectroscopic measurements, whereas the derivatives possessing the shorter
      tethered moiety exhibit interesting addition patterns on C60 and C70 . 

PMID- 25853852
TI  - Increased biodiversity in the environment improves the humoral response of rats.
AB  - Previous studies have compared the immune systems of wild and of laboratory
      rodents in an effort to determine how laboratory rodents differ from their
      naturally occurring relatives. This comparison serves as an indicator of what
      sorts of changes might exist between modern humans living in Western culture
      compared to our hunter-gatherer ancestors. However, immunological experiments on
      wild-caught animals are difficult and potentially confounded by increased levels
      of stress in the captive animals. In this study, the humoral immune responses of
      laboratory rats in a traditional laboratory environment and in an environment
      with enriched biodiversity were examined following immunization with a panel of
      antigens. Biodiversity enrichment included colonization of the laboratory animals
      with helminths and co-housing the laboratory animals with wild-caught rats.
      Increased biodiversity did not apparently affect the IgE response to peanut
      antigens following immunization with those antigens. However, animals housed in
      the enriched biodiversity setting demonstrated an increased mean humoral response
      to T-independent and T-dependent antigens and increased levels of "natural"
      antibodies directed at a xenogeneic protein and at an autologous tissue extract
      that were not used as immunogens. 

PMID- 25853853
TI  - Ultrastrong Mode Confinement in ZnO Surface Plasmon Nanolasers.
AB  - Nanolasers with an ultracompact footprint can provide high-intensity coherent
      light, which can be potentially applied to high-capacity signal processing,
      biosensing, and subwavelength imaging. Among various nanolasers, those with
      cavities surrounded by metals have been shown to have superior light emission
      properties because of the surface plasmon effect that provides enhanced field
      confinement capability and enables exotic light-matter interaction. In this
      study, we demonstrated a robust ultraviolet ZnO nanolaser that can operate at
      room temperature by using silver to dramatically shrink the mode volume. The
      nanolaser shows several distinct features including an extremely small mode
      volume, a large Purcell factor, and a slow group velocity, which ensures strong
      interaction with the exciton in the nanowire. 

PMID- 25853854
TI  - Correction: thermodynamics of random reaction networks.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0117312.]. 

PMID- 25853855
TI  - Investigation of genes encoding calcineurin B-like protein family in legumes and
      their expression analyses in chickpea (Cicer arietinum L.).
AB  - Calcium ion (Ca2+) is a ubiquitous second messenger that transmits various
      internal and external signals including stresses and, therefore, is important for
      plants' response process. Calcineurin B-like proteins (CBLs) are one of the plant
      calcium sensors, which sense and convey the changes in cytosolic Ca2+
      concentration for response process. A search in four leguminous plant (soybean,
      Medicago truncatula, common bean and chickpea) genomes identified 9 to 15 genes
      in each species that encode CBL proteins. Sequence analyses of CBL peptides and
      coding sequences (CDS) suggested that there are nine original CBL genes in these
      legumes and some of them were multiplied during whole genome or local gene
      duplication. Coding sequences of chickpea CBL genes (CaCBL) were cloned from
      their cDNAs and sequenced, and their annotations in the genome assemblies were
      corrected accordingly. Analyses of protein sequences and gene structures of CBL
      family in plant kingdom indicated its diverse origin but showed a remarkable
      conservation in overall protein structure with appearance of complex gene
      structure in the course of evolution. Expression of CaCBL genes in different
      tissues and in response to different stress and hormone treatment were studied.
      Most of the CaCBL genes exhibited high expression in flowers. Expression profile
      of CaCBL genes in response to different abiotic stresses and hormones related to
      development and stresses (ABA, auxin, cytokinin, SA and JA) at different time
      intervals suggests their diverse roles in development and plant defence in
      addition to abiotic stress tolerance. These data not only contribute to a better
      understanding of the complex regulation of chickpea CBL gene family, but also
      provide valuable information for further research in chickpea functional
      genomics. 

PMID- 25853856
TI  - Singing from the grave: DNA from a 180 year old type specimen confirms the
      identity of Chrysoperla carnea (Stephens).
AB  - Historically serving as repositories for morphologically-based taxonomic
      research, natural history collections are now increasingly being targeted in
      studies utilizing DNA data. The development of advanced molecular techniques has
      facilitated extraction of useable DNA from old specimens, including type
      material. Sequencing diagnostic molecular markers from type material enables
      accurate species designation, especially where modern taxonomic hypotheses
      confirm morphologically cryptic species complexes. One such example is
      Chrysoperla carnea (Stephens), which belongs to a complex of about 20 cryptic
      species, most of which can only be reliably distinguished by their pre-mating
      courtship songs or by DNA analysis. The subtle morphological variation in the
      group has led to disagreement over the previous designation of the lectotype for
      C. carnea, an issue that has been further compounded because Chrysoperla carnea
      is a highly valued biological control agent in arable crops. Archival DNA
      extraction and sequencing from the 180 year old lectotype specimen, combined with
      Bayesian and Likelihood based phylogenetic analyses of modern specimens from the
      entire complex, were used to establish unambiguously the true identity of
      Chrysoperla carnea. 

PMID- 25853857
TI  - Single administration of ultra-low-dose lipopolysaccharide in rat early pregnancy
      induces TLR4 activation in the placenta contributing to preeclampsia.
AB  - Balanced immune responses are essential for the maintenance of successful
      pregnancy. Aberrant responses of immune system during pregnancy increase the risk
      of preeclampsia. Toll-like receptor 4 (TLR4) plays a crucial role in the
      activation of immune system at the maternal-fetal interface. This study aimed to
      generate a rat model of preeclampsia by lipopolysaccharide (LPS, a TLR4 agonist)
      administration on gestational day (GD) 5 as rats are subjected to placentation
      immediately after implantation between GDs 4 and 5, and to assess the
      contribution of TLR4 signaling to the development of preeclampsia. Single
      administration of 0.5 MUg/kg LPS significantly increased blood pressure of
      pregnant rats since GD 6 (systolic blood pressure, 124.89 +/- 1.79 mmHg versus
      119.02 +/- 1.80 mmHg, P < 0.05) and urinary protein level since GD 9 (2.02 +/-
      0.29 mg versus 1.11 +/- 0.18 mg, P < 0.01), but barely affected blood pressure or
      proteinuria of virgin rats compared with those of saline-treated pregnant rats.
      This was accompanied with adverse pregnancy outcomes including fetal growth
      restriction. The expression of TLR4 and NF-kappaB p65 were both increased in the
      placenta but not the kidney from LPS-treated pregnant rats, with deficient
      trophoblast invasion and spiral artery remodeling. Furthermore, the levels of
      inflammatory cytokines were elevated systemically and locally in the placenta
      from pregnant rats treated with LPS. TLR4 signaling in the placenta was
      activated, to which that in the placenta of humans with preeclampsia changed
      similarly. In conclusion, LPS administration to pregnant rats in early pregnancy
      could elicit TLR4-mediated immune response at the maternal-fetal interface
      contributing to poor early placentation that may culminate in the preeclampsia
      like syndrome. 

PMID- 25853858
TI  - Metabolomic method: UPLC-q-ToF polar and non-polar metabolites in the healthy rat
      cerebellum using an in-vial dual extraction.
AB  - Unbiased metabolomic analysis of biological samples is a powerful and
      increasingly commonly utilised tool, especially for the analysis of bio-fluids to
      identify candidate biomarkers. To date however only a small number of metabolomic
      studies have been applied to studying the metabolite composition of tissue
      samples, this is due, in part to a number of technical challenges including
      scarcity of material and difficulty in extracting metabolites. The aim of this
      study was to develop a method for maximising the biological information obtained
      from small tissue samples by optimising sample preparation, LC-MS analysis and
      metabolite identification. Here we describe an in-vial dual extraction (IVDE)
      method, with reversed phase and hydrophilic liquid interaction chromatography
      (HILIC) which reproducibly measured over 4,000 metabolite features from as little
      as 3mg of brain tissue. The aqueous phase was analysed in positive and negative
      modes following HILIC separation in which 2,838 metabolite features were
      consistently measured including amino acids, sugars and purine bases. The non
      aqueous phase was also analysed in positive and negative modes following reversed
      phase separation gradients respectively from which 1,183 metabolite features were
      consistently measured representing metabolites such as phosphatidylcholines,
      sphingolipids and triacylglycerides. The described metabolomics method includes a
      database for 200 metabolites, retention time, mass and relative intensity, and
      presents the basal metabolite composition for brain tissue in the healthy rat
      cerebellum. 

PMID- 25853859
TI  - Synchronous rhythmic interaction enhances children's perceived similarity and
      closeness towards each other.
AB  - Inter-personal synchronization is important for performing many cooperative
      tasks. Notably, synchrony has also been shown to have considerable positive
      social influences, possibly mediated by synchrony-induced changes in social
      attitude such as an increased sense of similarity and affiliation between
      interacting individuals. This effect has been demonstrated in adults, but it is
      unknown whether synchrony might have a similar impact on the social attitudes of
      children. We thus set to directly examine the influence of synchronous rhythmic
      interaction on perceived similarity and closeness in pairs of 8-9 year old
      children. We found that children who had participated in a synchronous
      interaction regarded their interacting partner as more similar and closer to
      themselves than children who had not interacted at all or who had taken part in
      an asynchronous interaction. These findings reveal that synchronous interaction
      can positively alter social attitudes between interacting children, suggesting a
      potential mechanism by which synchrony may enhance positive social interaction
      through attitudinal shift. 

PMID- 25853861
TI  - Correction: Abiotic racemization kinetics of amino acids in marine sediments.

PMID- 25853860
TI  - Immunophenotyping of Waldenstroms macroglobulinemia cell lines reveals distinct
      patterns of surface antigen expression: potential biological and therapeutic
      implications.
AB  - Waldenstroms macroglobulinemia (WM) is a subtype of Non-Hodgkin's lymphoma in
      which the tumor cell population is markedly heterogeneous, consisting of
      immunoglobulin-M secreting B-lymphocytes, plasmacytoid lymphocytes and plasma
      cells. Due to rarity of disease and scarcity of reliable preclinical models, many
      facets of WM molecular and phenotypic architecture remain incompletely
      understood. Currently, there are 3 human WM cell lines that are routinely used in
      experimental studies, namely, BCWM.1, MWCL-1 and RPCI-WM1. During establishment
      of RPCI-WM1, we observed loss of the CD19 and CD20 antigens, which are typically
      present on WM cells. Intrigued by this observation and in an effort to better
      define the immunophenotypic makeup of this cell line, we conducted a more
      comprehensive analysis for the presence or absence of other cell surface antigens
      that are present on the RPCI-WM1 model, as well as those on the two other WM cell
      lines, BCWM.1 and MWCL-1. We examined expression of 65 extracellular and 4
      intracellular antigens, comprising B-cell, plasma cell, T-cell, NK-cell, myeloid
      and hematopoietic stem cell surface markers by flow cytometry analysis. RPCI-WM1
      cells demonstrated decreased expression of CD19, CD20, and CD23 with enhanced
      expression of CD28, CD38 and CD184, antigens that were differentially expressed
      on BCWM.1 and MWCL-1 cells. Due to increased expression of CD184/CXCR4 and CD38,
      RPCI-WM1 represents a valuable model in which to study the effects anti-CXCR4 or
      anti-CD38 targeted therapies that are actively being developed for treatment of
      hematologic cancers. Overall, differences in surface antigen expression across
      the 3 cell lines may reflect the tumor clone population predominant in the index
      patients, from whom the cell lines were developed. Our analysis defines the
      utility of the most commonly employed WM cell lines as based on their
      immunophenotype profiles, highlighting unique differences that can be further
      studied for therapeutic exploit. 

PMID- 25853862
TI  - Peripheral opioid antagonist enhances the effect of anti-tumor drug by blocking a
      cell growth-suppressive pathway in vivo.
AB  - The dormancy of tumor cells is a major problem in chemotherapy, since it limits
      the therapeutic efficacy of anti-tumor drugs that only target dividing cells. One
      potential way to overcome chemo-resistance is to "wake up" these dormant cells.
      Here we show that the opioid antagonist methylnaltrexone (MNTX) enhances the
      effect of docetaxel (Doc) by blocking a cell growth-suppressive pathway. We found
      that PENK, which encodes opioid growth factor (OGF) and suppresses cell growth,
      is predominantly expressed in diffuse-type gastric cancers (GCs). The blockade of
      OGF signaling by MNTX releases cells from their arrest and boosts the effect of
      Doc. In comparison with the use of Doc alone, the combined use of Doc and MNTX
      significantly prolongs survival, alleviates abdominal pain, and diminishes Doc
      resistant spheroids on the peritoneal membrane in model mice. These results
      suggest that blockade of the pathways that suppress cell growth may enhance the
      effects of anti-tumor drugs. 

PMID- 25853863
TI  - Glucocorticoids suppress GLP-1 secretion: possible contribution to their
      diabetogenic effects.
AB  - Evidence indicates that subtle abnormalities in GC (glucocorticoid) plasma
      concentrations and/or in tissue sensitivity to GCs are important in the metabolic
      syndrome, and it is generally agreed that GCs induce insulin resistance. In
      addition, it was recently reported that short-term exposure to GCs reduced the
      insulinotropic effects of the incretin GLP-1 (glucagon-like peptide 1). However,
      although defective GLP-1 secretion has been correlated with insulin resistance,
      potential direct effects of GCs on GLP-1-producing L-cell function in terms of
      GLP-1 secretion and apoptosis have not been studied in any greater detail. In the
      present study, we sought to determine whether GCs could exert direct effects on
      GLP-1-producing L-cells in terms of GLP-1 secretion and cell viability. We
      demonstrate that the GR (glucocorticoid receptor) is expressed in GLP-1-producing
      cells, where GR activation in response to dexamethasone induces SGK1 (serum- and
      glucocorticoid-inducible kinase 1) expression, but did not influence
      preproglucagon expression or cell viability. In addition, dexamethasone treatment
      of enteroendocrine GLUTag cells reduced GLP-1 secretion induced by glucose, 2
      deoxy-D-glucose, fructose and potassium, whereas the secretory response to a
      phorbol ester was unaltered. Furthermore, in vivo administration of dexamethasone
      to rats reduced the circulating levels of GLP-1 concurrent with induction of
      insulin resistance and glucose intolerance. We can conclude that GR activation in
      GLP-1-producing cells will diminish the secretory responsiveness of these cells
      to subsequent carbohydrate stimulation. These effects may not only elucidate the
      pathogenesis of steroid diabetes, but could ultimately contribute to the
      identification of novel molecular targets for controlling incretin secretion. 

PMID- 25853864
TI  - TDP-43 as a possible biomarker for frontotemporal lobar degeneration: a
      systematic review of existing antibodies.
AB  - Frontotemporal lobar degeneration (FTLD) is one of the leading causes of dementia
      after Alzheimer's disease. A high-ranking candidate to become a diagnostic marker
      for a major pathological subtype of FTLD is the transactive response DNA binding
      protein of 43 kDa (TDP-43). The main objective is to elucidate which antibodies
      are specific for pathological TDP-43, with special interest in its modified
      isoforms. Indeed, TDP-43 has been shown to be hyperphosphorylated and truncated
      in disease. A secondary objective is to review existing immunoassays that
      quantify TDP-43 in biofluids. A systematic review of literature was performed by
      searching PubMed and Web of Science using predefined keywords. Of considered
      research papers the methods section was reviewed to select publications that
      enabled us to answer our learning objective. After quality assessment, antibody
      characteristics and related outcomes were extracted. We identified a series of
      well-characterized antibodies based on a scoring system that assessed the ability
      of each antibody to detect TDP-43 pathology. A selection of 29 unique antibodies
      was made comprising 10 high-ranking antibodies which were reported multiple times
      to detect TDP-43 pathology in both immunostaining and immunoblotting experiments
      and 19 additional antibodies which detected TDP-43 pathology but were only scored
      once. This systematic review provides an overview of antibodies that are reported
      to detect pathological TDP-43. These antibodies can be used in future studies of
      TDP-43 proteinopathies. Additionally, selected antibodies hold the potential to
      be used in the development of novel immunoassays for the quantification of TDP-43
      in biofluids, as a possible biomarker for FTLD-TDP.

PMID- 25853865
TI  - Delay of Surgery for Melanoma Among Medicare Beneficiaries.
AB  - IMPORTANCE: Timely delivery of surgery for cancer affects health care quality and
      outcomes. However, population-based studies characterizing the delay of surgery
      for melanoma in the United States have not been performed. OBJECTIVE: To assess
      the delay of surgery for melanoma by tumor-, patient-, and physician-level
      characteristics. DESIGN, SETTING, AND PARTICIPANTS: We performed a retrospective
      cohort study of Medicare beneficiaries diagnosed as having melanoma from January
      1, 2000, through December 31, 2009, using the Surveillance, Epidemiology, and End
      Results-Medicare database. We included all patients undergoing surgical excision
      of melanoma diagnosed by means of results of skin biopsy. EXPOSURES: Anatomic
      location and stage of the tumor, patient sociodemographic characteristics, prior
      melanoma, Elixhauser comorbidities, and the specialties of the physicians who
      performed the biopsy and surgery. MAIN OUTCOMES AND MEASURES: Surgical delay,
      measured as the time from the biopsy to surgical excision. We estimated risk
      adjusted odds ratios (ORs) and marginal probabilities of delay with 95% CIs for
      each covariate using mixed-effects logistic regression. RESULTS: Our cohort
      consisted of 32 501 cases of melanoma. Most of the patients were white (95.4%),
      male (63.1%), married (47.9%), and 75 years or older (60.8%) and did not have a
      prior melanoma (93.7%). Melanomas were most frequently located on the head and
      neck (40.5%) and staged as in situ disease (48.2%). More than three-quarters of
      cases (25 269 [77.7%]) underwent excision within 1.5 months of biopsy. Among
      those treated after 1.5 months (7232 [22.3%]), 2620 (8.1% of all cases)
      experienced a delay of longer than 3 months. The incidence of a risk-adjusted
      surgical delay longer than 1.5 months was significantly increased among patients
      85 years or older compared with those younger than 65 years (odds ratio [OR],
      1.28 [95% CI, 1.05-1.55]; P = .02), those with a prior melanoma (OR, 1.20 [95%
      CI, 1.08-1.34]; P = .001), and those with an increased comorbidity burden (OR,
      1.18 [95% CI, 1.09-1.27]; P < .001). Melanomas that underwent biopsy and excision
      by dermatologists had the lowest likelihood of delay (probability, 16% [95% CI,
      14%-18%]). The highest likelihood of delay (probability, 31% [95% CI, 24%-37%])
      occurred when the biopsy was performed by a nondermatologist and excised by a
      primary care physician. Similar findings were observed for a delay longer than 3
      months. CONCLUSIONS AND RELEVANCE: Approximately 1 in 5 Medicare beneficiaries
      experience a delay of surgery for melanoma that is longer than 1.5 months. Those
      patients undergoing biopsy and surgery by dermatologists have the lowest risk for
      delay, highlighting potential opportunities for improved access to and
      coordination of dermatologic care.

PMID- 25853866
TI  - Identification and fine mapping of nuclear and nucleolar localization signals
      within the human ribosomal protein S17.
AB  - Human ribosomal protein S17 (RPS17) is mutated in Diamond-Blackfan Anemia (DBA),
      a bone marrow disorder that fails to produce sufficient red blood cells leading
      to anemia. Recently, an RPS17 protein sequence was also found to be naturally
      inserted in the genome of hepatitis E virus (HEV) from patients chronically
      infected by HEV. The role of RPS17 in HEV replication and pathogenesis remains
      unknown due to the lack of knowledge about how RPS17 functions at a molecular
      level. Understanding the biological function of RPS17 is critical for elucidating
      its role in virus infection and DBA disease processes. In this study we probed
      the subcellular distribution of normal and mutant RPS17 proteins in a human liver
      cell line (Huh7). RPS17 was primarily detected within the nucleus, and more
      specifically within the nucleoli. Using a transient expression system in which
      RPS17 or truncations were expressed as fusions with enhanced yellow fluorescent
      protein (eYFP), we were able to identify and map, for the first time, two
      separate nuclear localization signals (NLSs), one to the first 13 amino acids of
      the amino-terminus of RPS17 and the other within amino acids 30-60. Additionally,
      we mapped amino acid sequences required for nucleolar accumulation of RPS17 to
      amino acids 60-70. Amino acids 60-70 possess a di-RG motif that may be necessary
      for nucleolar retention of RPS17. The results from this study enhance our
      knowledge of RSP17 and will facilitate future mechanistic studies about the roles
      of RSP17 in hepatitis E and DBA disease processes. 

PMID- 25853867
TI  - Inhaled nitric oxide in term/late preterm neonates with hypoxic respiratory
      failure: estimating the financial impact of earlier use.
AB  - OBJECTIVE: We reported recently that early use of inhaled nitric oxide therapy
      (iNO) for term and late preterm infants with hypoxic respiratory failure (HRF) at
      an oxygenation index (OI) of >=15 and <20 is associated with earlier discharge
      from the hospital, relative to babies treated at OI >=25. The objective of the
      present analysis is to determine whether earlier use of iNO in this cohort leads
      to lower cost of medical care. METHODS: We used a decision-analytic model, which
      was developed to compare hospital resource use and costs associated with early
      versus standard use of iNO in HRF. The model population included infants with
      moderate HRF caused by primary pulmonary hypertension with an OI >=15 and <20. A
      hypothetical case population of 1000 patients was assumed and probabilistic
      sensitivity analyses were completed where all the clinical inputs into the model
      were varied. Two deterministic sensitivity analyses were also completed, one
      surrounding the hospital cost inputs and another surrounding the cost of iNO.
      RESULTS: Early iNO was associated with fewer hospital days, fewer days of
      ventilation and fewer hours on extracorporeal membrane oxygenation (ECMO). In
      probabilistic sensitivity analyses, total costs per patient were $88,518 +/-
      $7574 and $92,581 +/- $9664 for early iNO and standard iNO, respectively. The
      probability of early iNO being cost-effective was approximately 72%, based on a
      willingness to pay $100,000 or less to prevent ECMO therapy and/or death. In both
      deterministic sensitivity analyses, early iNO was cost-saving. CONCLUSION: Our
      analysis shows that early use of iNO at an OI of >=15 and <20 may be associated
      with shorter hospitalizations and a decreased cost of care for term/late preterm
      infants with HRF associated with pulmonary hypertension. Our results are based on
      clinical data from a single trial; future research using data from real-world
      practice is warranted.

PMID- 25853868
TI  - Cost-effectiveness of once daily GLP-1 receptor agonist lixisenatide compared to
      bolus insulin both in combination with basal insulin for the treatment of
      patients with type 2 diabetes in Norway.
AB  - BACKGROUND: Lixisenatide is a potent, selective and short-acting once daily
      prandial glucagon-like peptide-1 receptor agonist which lowers glycohemoglobin
      and body weight by clinically significant amounts in patients with type 2
      diabetes treated with basal insulin, with limited risk of hypoglycemia.
      OBJECTIVE: To assess the cost-effectiveness of lixisenatide versus bolus insulin,
      both in combination with basal insulin, in patients with type 2 diabetes in
      Norway. METHODS: The IMS CORE Diabetes Model, a non-product-specific and
      validated simulation model, was used to make clinical and cost projections.
      Transition probabilities, risk adjustments and the progression of complication
      risk factors were derived from the UK Prospective Diabetes Study, supplemented
      with Norwegian data. Patients were assumed to receive combination treatment with
      basal insulin, lixisenatide or bolus insulin therapy for 3 years, followed by
      intensification of a basal-bolus insulin regimen for their remaining lifetime.
      Simulated healthcare costs, taken from the public payer perspective, were derived
      from microcosting and diagnosis related groups, discounted at 4% per annum and
      reported in Norwegian krone (NOK). Productivity costs were also captured based on
      extractions from the Norwegian Labor and Welfare Administration. Health state
      utilities were derived from a systematic literature review. Sensitivity and
      scenario analyses were performed. RESULTS: Lixisenatide in combination with basal
      insulin was associated with increased quality-adjusted life years (QALYs) and
      reduced lifetime healthcare costs compared to bolus insulin in combination with
      basal insulin in patients with Type 2 diabetes, and can be considered dominant.
      The net monetary benefit of lixisenatide versus bolus insulin was NOK 39,369 per
      patient. Results were sensitive to discounting, the application of excess body
      weight associated disutility and uncertainty surrounding the changes in HbA1c.
      CONCLUSIONS: Lixisenatide may be considered an economically efficient therapy in
      combination with basal insulin in the Norwegian setting, due to cost savings,
      weight loss and associated gains in health-related quality of life.

PMID- 25853869
TI  - Finger muscle attachments for an OpenSim upper-extremity model.
AB  - We determined muscle attachment points for the index, middle, ring and little
      fingers in an OpenSim upper-extremity model. Attachment points were selected to
      match both experimentally measured locations and mechanical function (moment
      arms). Although experimental measurements of finger muscle attachments have been
      made, models differ from specimens in many respects such as bone segment ratio,
      joint kinematics and coordinate system. Likewise, moment arms are not available
      for all intrinsic finger muscles. Therefore, it was necessary to scale and
      translate muscle attachments from one experimental or model environment to
      another while preserving mechanical function. We used a two-step process. First,
      we estimated muscle function by calculating moment arms for all intrinsic and
      extrinsic muscles using the partial velocity method. Second, optimization using
      Simulated Annealing and Hooke-Jeeves algorithms found muscle-tendon paths that
      minimized root mean square (RMS) differences between experimental and modeled
      moment arms. The partial velocity method resulted in variance accounted for (VAF)
      between measured and calculated moment arms of 75.5% on average (range from 48.5%
      to 99.5%) for intrinsic and extrinsic index finger muscles where measured data
      were available. RMS error between experimental and optimized values was within
      one standard deviation (S.D) of measured moment arm (mean RMS error = 1.5 mm <
      measured S.D = 2.5 mm). Validation of both steps of the technique allowed for
      estimation of muscle attachment points for muscles whose moment arms have not
      been measured. Differences between modeled and experimentally measured muscle
      attachments, averaged over all finger joints, were less than 4.9 mm (within 7.1%
      of the average length of the muscle-tendon paths). The resulting non-proprietary
      musculoskeletal model of the human fingers could be useful for many applications,
      including better understanding of complex multi-touch and gestural movements. 

PMID- 25853870
TI  - The impact of gender norms on condom use among HIV-positive adults in KwaZulu
      Natal, South Africa.
AB  - Critical to preventing the spread of HIV is promoting condom use among HIV
      positive individuals. Previous studies suggest that gender norms (social and
      cultural constructions of the ways that women and men are expected to behave) may
      be an important determinant of condom use. However, the relationship has not been
      evaluated among HIV-positive women and men in South Africa. We examined gender
      norms and condom use at last sex among 550 partnerships reported by 530 sexually
      active HIV-positive women (372) and men (158) who had sought care, but not yet
      initiated antiretroviral therapy in a high HIV-prevalence rural setting in
      KwaZulu-Natal, South Africa between January 2009 and March 2011. Participants
      enrolled in the cohort study completed a baseline questionnaire that detailed
      their socio-demographic characteristics, socio-economic circumstances, religion,
      HIV testing history and disclosure of HIV status, stigma, social capital, gender
      norms and self-efficacy. Gender norms did not statistically differ between women
      and men (p = 0.18). Overall, condoms were used at last sex in 58% of
      partnerships. Although participants disclosed their HIV status in 66% of the
      partnerships, 60% did not have knowledge of their partner's HIV status. In
      multivariable logistic regression, run separately for each sex, women younger
      than 26 years with more equitable gender norms were significantly more likely to
      have used a condom at last sex than those of the same age group with inequitable
      gender norms (OR = 8.88, 95% CI 2.95-26.75); the association between condom use
      and gender norms among women aged 26+ years and men of all ages was not
      statistically significant. Strategies to address gender inequity should be
      integrated into positive prevention interventions, particularly for younger
      women, and supported by efforts at a societal level to decrease gender
      inequality. 

PMID- 25853871
TI  - Assay reproducibility in clinical studies of plasma miRNA.
AB  - There are increasing reports of plasma miRNAs as biomarkers of human disease but
      few standards in methodologic reporting, leading to inconsistent data. We
      systematically reviewed plasma miRNA studies published between July 2013-June
      2014 to assess methodology. Six parameters were investigated: time to plasma
      extraction, methods of RNA extraction, type of miRNA, quantification, cycle
      threshold (Ct) setting, and methods of statistical analysis. We compared these
      data with a proposed standard methodologic technique. Beginning with initial
      screening for 380 miRNAs using microfluidic array technology and validation in an
      additional cohort of patients, we compared 11 miRNAs that exhibited differential
      expression between 16 patients with benign colorectal neoplasms (advanced
      adenomas) and 16 patients without any neoplasm (controls). Plasma was isolated
      immediately, 12, 24, 48, or 72 h following phlebotomy. miRNA was extracted using
      two different techniques (Trizol LS with pre-amplification or modified miRNeasy).
      We performed Taqman-based RT-PCR assays for the 11 miRNAs with subsequent
      analyses using a variable Ct setting or a fixed Ct set at 0.01, 0.03, 0.05, or
      0.5. Assays were performed in duplicate by two different operators. RNU6 was the
      internal reference. Systematic review yielded 74 manuscripts meeting inclusion
      criteria. One manuscript (1.4%) documented all 6 methodological parameters, while
      < 5% of studies listed Ct setting. In our proposed standard technique, plasma
      extraction <=12 h provided consistent DeltaCt. miRNeasy extraction yielded higher
      miRNA concentrations and fewer non-expressed miRNAs compared to Trizol LS (1/704
      miRNAs [0.14%] vs 109/704 miRNAs [15%], not expressed, respectively). A fixed Ct
      bar setting of 0.03 yielded the most reproducible data, provided that <10% miRNA
      were non-expressed. There was no significant intra-operator variability. There
      was significant inter-operator variation using Trizol LS extraction, while this
      was negligible using modified miRNeasy. For standardized reporting, we recommend
      plasma extraction <= 12 h, using modified miRNeasy extraction and utilizing a
      0.03 Ct. 

PMID- 25853874
TI  - World gastroenterology organisation global guidelines: dysphagia--global
      guidelines and cascades update September 2014.

PMID- 25853872
TI  - Magnetization transfer imaging of suicidal patients with major depressive
      disorder.
AB  - Magnetization transfer imaging (MTI) provides a quantitative measure of the
      macromolecular structural integrity of brain tissue, as represented by
      magnetization transfer ratio (MTR). In this study, we utilized MTI to identify
      biophysical alterations in MDD patients with a history of suicide attempts
      relative to MDD patients without such history. The participants were 36
      medication-free MDD patients, with (N = 17) and without (N = 19) a history of a
      suicide attempt, and 28 healthy controls matched for age and gender. Whole brain
      voxel-based analysis was used to compare MTR across three groups and to analyze
      correlations with symptom severity and illness duration. We identified decreased
      MTR in left inferior parietal lobule and right superior parietal lobule in
      suicide attempters relative to both non-attempters and controls. Non-attempters
      also showed significantly reduced MTR in left inferior parietal lobule relative
      to controls, as well as an MTR reduction in left cerebellum. These abnormalities
      were not correlated with symptom severity or illness duration. Depressed patients
      with a history of suicide attempt showed bilateral abnormalities in parietal
      cortex compared to nonsuicidal depressed patients and healthy controls. Parietal
      lobe abnormalities might cause attentional dysfunction and impaired decision
      making to increase risk for suicidal behavior in MDD. 

PMID- 25853875
TI  - World digestive health day, heartburn: a Global Perspective and Gastro 2015!

PMID- 25853876
TI  - Short-term effect of crunch exercise frequency on abdominal muscle endurance.
AB  - Despite core exercise programs are broadly used to increase muscle function and
      to promote low back health, there is a lack of scientific evidence on some of the
      most important characteristics of trunk exercise programs, as for example
      training frequency. This study aimed to compare the short-term effect of training
      frequencies of 1, 2 and 3 days per week (d/wk) on abdominal muscle endurance in
      untrained adolescents. One hundred and eighteen high-school students (59 men and
      59 women) with no previous experience in structured abdominal exercise programs
      were assigned randomly to groups that trained 1 d/wk (G1; N.=21), 2 d/wk (G2;
      N.=27), 3 d/wk (G3; N.=23), or to a control group (CG; N.=47) that did not train.
      The training groups performed crunch and cross-crunch exercises 1, 2 or 3 d/wk
      during six weeks. Before and after the training period, the bench trunk-curl test
      (BTC test) was carried out to assess abdominal muscle endurance. Men obtained
      higher BTC test scores than women before and after training. Training frequencies
      of 1, 2 and 3 d/wk provided a significant increase in BTC test scores; however,
      no significant differences between the three groups' scores were found after
      training. Therefore, a small dose of crunch exercise training (1 d/wk) may be
      sufficient stimulus to increase abdominal endurance in untrained male and female
      adolescents, at least during the first weeks of an abdominal exercise program,
      which seems a very relevant finding in terms of time-cost efficiency. 

PMID- 25853877
TI  - Creatine supplementation alters homocysteine level in resistance trained men.
AB  - AIM: This study was conducted to investigate the effects of creatine loading and
      resistance training on the homocysteine and lipid profiles of young males.
      METHOD: Sixty male University students (22.34 +/- 2.19 years, 1.79 +/- 0.08 m,
      77.18 +/- 12.57 kg, 15.48 +/- 4.57% body fat) were randomly divided in to three
      groups; control (CG=20), creatine supplement (CEG=20) and placebo (PEG=20). Both
      CEG and PEG participated in a same resistance-training regimen and either taking
      a creatine supplement (25 g/d for the first 5 days followed 5 g/d thereafter) or
      the same amount of placebo for 8 weeks. Participants in CG did not take any
      creatine supplementation and not engage any exercise program. After the body
      composition were assessed, the homocysteine (Hcy) concentrations, blood lipids,
      folic acid and vitamin B12 levels of all the participants were measured at the
      beginning and end of the eight weeks of resistance training. RESULTS: The
      analysis of the data indicated that the Hcy levels of the CEG after resistance
      training and receiving the creatine supplement (9.33 +/- 4.60) was significantly
      lower than that of baseline (12.66 +/- 5.89) measurements, F(1,18)=12.28, P=0.00.
      No significant differences were seen in the Hcy levels of the PEG (15.01 +/-
      10.87) after 8 weeks of training and receiving a placebo (12.46 +/- 12.50),
      F(1,16)=4.65, P=0.05. Furthermore, there were no significant differences among
      groups in terms of Hcy levels, F(2,52)=1.72, P=0.19. CONCLUSION: The present
      study suggests that as well as strength gain; creatine supplementation with
      resistance training may afford some protection against emerging cardiovascular
      risk factors.

PMID- 25853878
TI  - Effects of acute total body resistance exercise on hormonal and cytokines changes
      in men and women.
AB  - AIM: Sex differences in exercise responses have implications for understanding
      sex-specific adaptations to exercise for performance and health. The purpose of
      this study was to verify the acute effects of a full body resistance exercise
      protocol on growth hormone (GH), testosterone (TT), cortisol, interleukin (IL)-6
      and IL-10 in men and women. METHODS: Fourteen healthy volunteers (7 men and 7
      women taking oral contraceptives) active and recreationally trained in resistance
      exercise were subjected to a resistance exercise session (3x8-10 RM) composed of
      10 exercises with rests periods of 90-120 seconds between sets. GH, TT, cortisol,
      IL-6 and IL-10 were assessed at pre-, immediate post- (IP) and 30 min
      postprotocol. RESULTS: Both men and women had a similar increase in GH (P<0.05)
      at IP in response to exercise. Significant effects of interaction between sex and
      time were observed for TT, cortisol and IL-6. In the men, an increase from pre
      was noted at IP and 30 min for TT, cortisol and IL-6. In the women there was no
      change in TT, cortisol and IL-6 concentration. There was no change in IL-10.
      CONCLUSION: Our findings indicate a difference between men and women taking oral
      contraceptives in TT, cortisol and IL-6 responsiveness to the same full body
      resistance exercise protocol.

PMID- 25853879
TI  - Acute exercise increases hippocampal TNF-alpha, Caspase-3 and Caspase-7
      expression in healthy young and older mice.
AB  - AIM: Regular exercise may protect against cognitive decline by preventing central
      inflammation. The effect of an acute exercise bout on central cytokine and
      apoptotic protein expression is not known. The brain may be protected from
      transient oxidative stress such as that induced by acute-exercise. The purpose of
      this exploratory study was to determine the effect of a single bout of intense
      exercise on hippocampal expression of inflammatory mediators (TNF-alpha) and
      apoptotic proteins (caspase-3, caspase-7), and to evaluate any potential age
      related differences. METHODS: Using a C57BL/6 mouse model (N.=98), we evaluated
      the effect of an acute exercise bout (90 minutes of treadmill running: 10 min
      warm-up, 30 min at 22 m.min-1, 30 min at 25 m.min-1, and 30 min at 28 m.min-1, 2
      degrees  slope) on hippocampal inflammation in young (3-4 months), middle-aged
      (13-14 months) and older (16-17 months) C57BL/6 mice. RESULTS: Our results show
      post-exercise increases in hippocampal TNF-alpha and caspase-3/7 in each age
      group (main effect of acute exercise, P<0.05). Older mice displayed higher TNF
      alpha (main effect of age, P<0.05) expression compared with younger animals at
      baseline. Young mice demonstrated greater increases in caspase-7 following acute
      exercise, compared to older mice (interaction effect for caspase-7, P<0.05).
      CONCLUSION: Given the relationship between aging, inflammation and
      neurodegenerative disease, and the protective effects of exercise, we cautiously
      propose that acute-exercise induced inflammation may be a normal physiologic
      response that elicits a favorable (anti-inflammatory) hippocampal environment.

PMID- 25853880
TI  - Solomon Islands largest hawksbill turtle rookery shows signs of recovery after
      150 years of excessive exploitation.
AB  - The largest rookery for hawksbill turtles in the oceanic South Pacific is the
      Arnavon Islands, which are located in the Manning Strait between Isabel and
      Choiseul Province, Solomon Islands. The history of this rookery is one of
      overexploitation, conflict and violence. Throughout the 1800s Roviana headhunters
      from New Georgia repeatedly raided the Manning Strait to collect hawksbill shell
      which they traded with European whalers. By the 1970s the Arnavons hawksbill
      population was in severe decline and the national government intervened,
      declaring the Arnavons a sanctuary in 1976. But this government led initiative
      was short lived, with traditional owners burning down the government
      infrastructure and resuming intensive harvesting in 1982. In 1991 routine beach
      monitoring and turtle tagging commenced at the Arnavons along with extensive
      community consultations regarding the islands' future, and in 1995 the Arnavon
      Community Marine Conservation Area (ACMCA) was established. Around the same time
      national legislation banning the sale of all turtle products was passed. This
      paper represents the first analysis of data from 4536 beach surveys and 845
      individual turtle tagging histories obtained from the Arnavons between 1991-2012.
      Our results and the results of others, reveal that many of the hawksbill turtles
      that nest at the ACMCA forage in distant Australian waters, and that nesting on
      the Arnavons occurs throughout the year with peak nesting activity coinciding
      with the austral winter. Our results also provide the first known evidence of
      recovery for a western pacific hawksbill rookery, with the number of nests laid
      at the ACMCA and the remigration rates of turtles doubling since the
      establishment of the ACMCA in 1995. The Arnavons case study provides an example
      of how changes in policy, inclusive community-based management and long term
      commitment can turn the tide for one of the most charismatic and endangered
      species on our planet. 

PMID- 25853881
TI  - Relaxation effect of abacavir on rat basilar arteries.
AB  - BACKGROUND: The use of abacavir has been linked with increased cardiovascular
      risk in patients with human immunodeficiency virus infection; however, the
      mechanism involved remains unclear. We hypothesize that abacavir may impair
      endothelial function. In addition, based on the structural similarity between
      abacavir and adenosine, we propose that abacavir may affect vascular
      contractility through endogenous adenosine release or adenosine receptors in
      blood vessels. METHODS: The relaxation effect of abacavir on rat basilar arteries
      was studied using the myograph technique. Cyclic GMP and AMP levels were measured
      by immunoassay. The effects of abacavir on nucleoside transporters were studied
      using radiolabeled nucleoside uptake experiments. Ecto-5' nucleotidase activity
      was determined by measuring the generation of inorganic phosphate using adenosine
      monophosphate as the substrate. RESULTS: Abacavir induced the relaxation of rat
      basilar arteries in a concentration-dependent manner. This relaxation was
      abolished when endothelium was removed. In addition, the relaxation was
      diminished by the nitric oxide synthase inhibitor, L-NAME, the guanylyl cyclase
      inhibitor, ODQ, and the protein kinase G inhibitor, KT5820. Abacavir also
      increased the cGMP level in rat basilar arteries. Abacavir-induced relaxation was
      also abolished by adenosine A2 receptor blockers. However, abacavir had no effect
      on ecto-5' nucleotidase and nucleoside transporters. Short-term and long-term
      treatment of abacavir did not affect acetylcholine-induced relaxation in rat
      basilar arteries. CONCLUSION: Abacavir induces acute endothelium-dependent
      relaxation of rat basilar arteries, probably through the activation of adenosine
      A2 receptors in endothelial cells, which subsequently leads to the release of
      nitric oxide, resulting in activation of the cyclic guanosine
      monophosphate/protein kinase G-dependent pathway in vascular smooth muscle cells.
      It is speculated that abacavir-induced cardiovascular risk may not be related to
      endothelial dysfunction as abacavir does not impair relaxation of blood vessels.
      The most likely explanation of increased cardiovascular risk may be increased
      platelet aggregation as suggested by other studies.

PMID- 25853882
TI  - White matter integrity supports BOLD signal variability and cognitive performance
      in the aging human brain.
AB  - Decline in cognitive performance in old age is linked to both suboptimal neural
      processing in grey matter (GM) and reduced integrity of white matter (WM), but
      the whole-brain structure-function-cognition associations remain poorly
      understood. Here we apply a novel measure of GM processing-moment-to-moment
      variability in the blood oxygenation level-dependent signal (SDBOLD)-to study the
      associations between GM function during resting state, performance on four main
      cognitive domains (i.e., fluid intelligence, perceptual speed, episodic memory,
      vocabulary), and WM microstructural integrity in 91 healthy older adults (aged 60
      80 years). We modeled the relations between whole-GM SDBOLD with cognitive
      performance using multivariate partial least squares analysis. We found that
      greater SDBOLD was associated with better fluid abilities and memory. Most of
      regions showing behaviorally relevant SDBOLD (e.g., precuneus and insula) were
      localized to inter- or intra-network "hubs" that connect and integrate segregated
      functional domains in the brain. Our results suggest that optimal dynamic range
      of neural processing in hub regions may support cognitive operations that
      specifically rely on the most flexible neural processing and complex cross-talk
      between different brain networks. Finally, we demonstrated that older adults with
      greater WM integrity in all major WM tracts had also greater SDBOLD and better
      performance on tests of memory and fluid abilities. We conclude that SDBOLD is a
      promising functional neural correlate of individual differences in cognition in
      healthy older adults and is supported by overall WM integrity. 

PMID- 25853884
TI  - Visible-light-promoted remote C(sp(3))-H amidation and chlorination.
AB  - A visible-light-promoted C(sp(3))-H amidation and chlorination of N
      chlorosulfonamides (NCSs) is reported. This remote C(sp(3))-H functionalization
      can be achieved in weak basic solution at room temperature with as little as 0.1
      mol % of a photocatalyst. A variety of nitrogen-containing heterocycles (up to
      94% yield) and chlorides (up to 93% yield) are prepared from NCSs. Late-stage
      C(sp(3))-H functionalization of complex and biologically important (-)-cis
      myrtanylamine and (+)-dehydroabietylamine derivatives can also be achieved with
      excellent yields and regioselectivity. 

PMID- 25853883
TI  - Transcript and protein expression decoupling reveals RNA binding proteins and
      miRNAs as potential modulators of human aging.
AB  - BACKGROUND: In studies of development and aging, the expression of many genes has
      been shown to undergo drastic changes at mRNA and protein levels. The connection
      between mRNA and protein expression level changes, as well as the role of
      posttranscriptional regulation in controlling expression level changes in
      postnatal development and aging, remains largely unexplored. RESULTS: Here, we
      survey mRNA and protein expression changes in the prefrontal cortex of humans and
      rhesus macaques over developmental and aging intervals of both species'
      lifespans. We find substantial decoupling of mRNA and protein expression levels
      in aging, but not in development. Genes showing increased mRNA/protein disparity
      in primate brain aging form expression patterns conserved between humans and
      macaques and are enriched in specific functions involving mammalian target of
      rapamycin (mTOR) signaling, mitochondrial function and neurodegeneration.
      Mechanistically, aging-dependent mRNA/protein expression decoupling could be
      linked to a specific set of RNA binding proteins and, to a lesser extent, to
      specific microRNAs. CONCLUSIONS: Increased decoupling of mRNA and protein
      expression profiles observed in human and macaque brain aging results in specific
      co-expression profiles composed of genes with shared functions and shared
      regulatory signals linked to specific posttranscriptional regulators. Genes
      targeted and predicted to be targeted by the aging-dependent posttranscriptional
      regulation are associated with biological processes known to play important roles
      in aging and lifespan extension. These results indicate the potential importance
      of posttranscriptional regulation in modulating aging-dependent changes in humans
      and other species.

PMID- 25853885
TI  - Effect of genome and environment on metabolic and inflammatory profiles.
AB  - Twin and family studies have established the contribution of genetic factors to
      variation in metabolic, hematologic and immunological parameters. The majority of
      these studies analyzed single or combined traits into pre-defined syndromes. In
      the present study, we explore an alternative multivariate approach in which a
      broad range of metabolic, hematologic, and immunological traits are analyzed
      simultaneously to determine the resemblance of monozygotic (MZ) twin pairs, twin
      spouse pairs and unrelated, non-cohabiting individuals. A total of 517
      participants from the Netherlands Twin Register, including 210 MZ twin pairs and
      64 twin-spouse pairs, took part in the study. Data were collected on body
      composition, blood pressure, heart rate, and multiple biomarkers assessed in
      fasting blood samples, including lipid levels, glucose, insulin, liver enzymes,
      hematological measurements and cytokine levels. For all 51 measured traits, pair
      wise Pearson correlations, correcting for family relatedness, were calculated
      across all the individuals in the cohort. Hierarchical clustering techniques were
      applied to group the measured traits into sub-clusters based on similarity. Sub
      clusters were observed among metabolic traits and among inflammatory markers. We
      defined a phenotypic profile as the collection of all the traits measured for a
      given individual. Average within-pair similarity of phenotypic profiles was
      determined for the groups of MZ twin pairs, spouse pairs and pairs of unrelated
      individuals. The average similarity across the full phenotypic profile was higher
      for MZ twin pairs than for spouse pairs, and lowest for pairs of unrelated
      individuals. Cohabiting MZ twins were more similar in their phenotypic profile
      compared to MZ twins who no longer lived together. The correspondence in the
      phenotypic profile is therefore determined to a large degree by familial, mostly
      genetic, factors, while household factors contribute to a lesser degree to
      profile similarity. 

PMID- 25853886
TI  - ALDB: a domestic-animal long noncoding RNA database.
AB  - BACKGROUND: Long noncoding RNAs (lncRNAs) have attracted significant attention in
      recent years due to their important roles in many biological processes. Domestic
      animals constitute a unique resource for understanding the genetic basis of
      phenotypic variation and are ideal models relevant to diverse areas of biomedical
      research. With improving sequencing technologies, numerous domestic-animal
      lncRNAs are now available. Thus, there is an immediate need for a database
      resource that can assist researchers to store, organize, analyze and visualize
      domestic-animal lncRNAs. RESULTS: The domestic-animal lncRNA database, named
      ALDB, is the first comprehensive database with a focus on the domestic-animal
      lncRNAs. It currently archives 12,103 pig intergenic lncRNAs (lincRNAs), 8,923
      chicken lincRNAs and 8,250 cow lincRNAs. In addition to the annotations of
      lincRNAs, it offers related data that is not available yet in existing lncRNA
      databases (lncRNAdb and NONCODE), such as genome-wide expression profiles and
      animal quantitative trait loci (QTLs) of domestic animals. Moreover, a collection
      of interfaces and applications, such as the Basic Local Alignment Search Tool
      (BLAST), the Generic Genome Browser (GBrowse) and flexible search
      functionalities, are available to help users effectively explore, analyze and
      download data related to domestic-animal lncRNAs. CONCLUSIONS: ALDB enables the
      exploration and comparative analysis of lncRNAs in domestic animals. A user
      friendly web interface, integrated information and tools make it valuable to
      researchers in their studies. ALDB is freely available from
      http://res.xaut.edu.cn/aldb/index.jsp.

PMID- 25853888
TI  - Ornaments reveal resistance of North European cultures to the spread of farming.
AB  - The transition to farming is the process by which human groups switched from
      hunting and gathering wild resources to food production. Understanding how and to
      what extent the spreading of farming communities from the Near East had an impact
      on indigenous foraging populations in Europe has been the subject of lively
      debates for decades. Ethnographic and archaeological studies have shown that
      population replacement and admixture, trade, and long distance diffusion of
      cultural traits lead to detectable changes in symbolic codes expressed by
      associations of ornaments on the human body. Here we use personal ornaments to
      document changes in cultural geography during the Mesolithic-Neolithic
      transition. We submitted a binary matrix of 224 bead-types found at 212 European
      Mesolithic and 222 Early Neolithic stratigraphic units to a series of spatial and
      multivariate analyses. Our results reveal consistent diachronic and geographical
      trends in the use of personal ornaments during the Neolithisation. Adoption of
      novel bead-types combined with selective appropriation of old attires by incoming
      farmers is identified in Southern and Central Europe while cultural resistance
      leading to the nearly exclusive persistence of indigenous personal ornaments
      characterizes Northern Europe. We argue that this pattern reflects two distinct
      cultural trajectories with different potential for gene flow. 

PMID- 25853887
TI  - Hunting for the LCT-13910*T allele between the Middle Neolithic and the Middle
      Ages suggests its absence in dairying LBK people entering the Kuyavia region in
      the 8th millennium BP.
AB  - Populations from two medieval sites in Central Poland, Stary Brzesc Kujawski-4
      (SBK-4) and Gruczno, represented high level of lactase persistence (LP) as
      followed by the LCT-13910*T allele's presence (0.86 and 0.82, respectively). It
      was twice as high as in contemporaneous Cedynia (0.4) and Srodka (0.43), both
      located outside the region, higher than in modern inhabitants of Poland (0.51)
      and almost as high as in modern Swedish population (0.9). In an attempt to
      explain the observed differences its frequency changes in time were followed
      between the Middle Neolithic and the Late Middle Ages in successive dairying
      populations on a relatively small area (radius ~60km) containing the two sites.
      The introduction of the T allele to Kuyavia 7.4 Ka BP by dairying LBK people is
      not likely, as suggested by the obtained data. It has not been found in any of
      Neolithic samples dated between 6.3 and 4.5 Ka BP. The identified frequency
      profile indicates that both the introduction and the beginning of selection could
      have taken place approx. 4 millennia after first LBK people arrived in the
      region, shifting the value of LP frequency from 0 to more than 0.8 during less
      than 130 generations. We hypothesize that the selection process of the T allele
      was rather rapid, starting just after its introduction into already milking
      populations and operated via high rates of fertility and mortality on children
      after weaning through life-threatening conditions, favoring lactose-tolerant
      individuals. Facing the lack of the T allele in people living on two great
      European Neolithization routes, the Danubian and Mediterranean ones, and based on
      its high frequency in northern Iberia, its presence in Scandinavia and estimated
      occurrence in Central Poland, we propose an alternative Northern Route of its
      spreading as very likely. None of the successfully identified nuclear alleles
      turned out to be deltaF508 CFTR. 

PMID- 25853889
TI  - MYB elongation is regulated by the nucleic acid binding of NFkappaB p50 to the
      intronic stem-loop region.
AB  - MYB transcriptional elongation is regulated by an attenuator sequence within
      intron 1 that has been proposed to encode a RNA stem loop (SLR) followed by a
      polyU tract. We report that NFkappaBp50 can bind the SLR polyU RNA and promote
      MYB transcriptional elongation together with NFkappaBp65. We identified a
      conserved lysine-rich motif within the Rel homology domain (RHD) of NFkappaBp50,
      mutation of which abrogated the interaction of NFkappaBp50 with the SLR polyU and
      impaired NFkappaBp50 mediated MYB elongation. We observed that the TAR RNA
      binding region of Tat is homologous to the NFkappaBp50 RHD lysine-rich motif, a
      finding consistent with HIV Tat acting as an effector of MYB transcriptional
      elongation in an SLR dependent manner. Furthermore, we identify the DNA binding
      activity of NFkappaBp50 as a key component required for the SLR polyU mediated
      regulation of MYB. Collectively these results suggest that the MYB SLR polyU
      provides a platform for proteins to regulate MYB and reveals novel nucleic acid
      binding properties of NFkappaBp50 required for MYB regulation. 

PMID- 25853890
TI  - A systematic review of factors influencing student ratings in undergraduate
      medical education course evaluations.
AB  - BACKGROUND: Student ratings are a popular source of course evaluations in
      undergraduate medical education. Data on the reliability and validity of such
      ratings have mostly been derived from studies unrelated to medical education.
      Since medical education differs considerably from other higher education
      settings, an analysis of factors influencing overall student ratings with a
      specific focus on medical education was needed. METHODS: For the purpose of this
      systematic review, online databases (PubMed, PsycInfo and Web of Science) were
      searched up to August 1st, 2013. Original research articles on the use of student
      ratings in course evaluations in undergraduate medical education were eligible
      for inclusion. Included studies considered the format of evaluation tools and
      assessed the association of independent and dependent (i.e., overall course
      ratings) variables. Inclusion and exclusion criteria were checked by two
      independent reviewers, and results were synthesised in a narrative review.
      RESULTS: Twenty-five studies met the inclusion criteria. Qualitative research (2
      studies) indicated that overall course ratings are mainly influenced by student
      satisfaction with teaching and exam difficulty rather than objective determinants
      of high quality teaching. Quantitative research (23 studies) yielded various
      influencing factors related to four categories: student characteristics, exposure
      to teaching, satisfaction with examinations and the evaluation process itself.
      Female gender, greater initial interest in course content, higher exam scores and
      higher satisfaction with exams were associated with more positive overall course
      ratings. CONCLUSIONS: Due to the heterogeneity and methodological limitations of
      included studies, results must be interpreted with caution. Medical educators
      need to be aware of various influences on student ratings when developing data
      collection instruments and interpreting evaluation results. More research into
      the reliability and validity of overall course ratings as typically used in the
      evaluation of undergraduate medical education is warranted.

PMID- 25853891
TI  - Expanding the species and chemical diversity of Penicillium section
      Cinnamopurpurea.
AB  - A set of isolates very similar to or potentially conspecific with an unidentified
      Penicillium isolate NRRL 735, was assembled using a BLAST search of ITS
      similarity among described (GenBank) and undescribed Penicillium isolates in our
      laboratories. DNA was amplified from six loci of the assembled isolates and
      sequenced. Two species in section Cinnamopurpurea are self-compatible sexual
      species, but the asexual species had polymorphic loci suggestive of sexual
      reproduction and variation in conidium size suggestive of ploidy level
      differences typical of heterothallism. Accordingly we use genealogical
      concordance analysis, a technique valid only in heterothallic organisms, for
      putatively asexual species. Seven new species were revealed in the analysis and
      are described here. Extrolite analysis showed that two of the new species, P.
      colei and P. monsserratidens produce the mycotoxin citreoviridin that has
      demonstrated pharmacological activity against human lung tumors. These isolates
      could provide leads in pharmaceutical research. 

PMID- 25853893
TI  - Repeated sprint performance and metabolic recovery curves: effects of aerobic and
      anaerobic characteristics.
AB  - To examine the influence of aerobic and anaerobic indices on repeated sprint (RS)
      performance and ability (RSA), 8 sprinters (SPR), 8 endurance runners (END), and
      8 active participants (ACT) performed the following tests: (i) incremental test;
      (ii) 1-min test to determine first decay time constant of pulmonary oxygen uptake
      off-kinetics and parameters related to anaerobic energy supply, lactate exchange,
      and removal abilities from blood lactate kinetics; and (iii) RS test (ten 35-m
      sprints, departing every 20 s) to determine best (RSbest) and mean (RSmean)
      sprint times and percentage of sprint decrement (%Dec). While SPR had a 98%-100%
      likelihood of having the fastest RSbest (Cohen's d of 1.8 and 1.4 for ACT and
      END, respectively) and RSmean (2.1 and 0.9 for ACT and END, respectively), END
      presented a 97%-100% likelihood of having the lowest %Dec (0.9 and 2.2 for ACT
      and SPR, respectively). RSmean was very largely correlated with RSbest (r=0.85)
      and moderately correlated with estimates of anaerobic energy supply (r=-0.40 to 
      0.49). RSmean adjusted for RSbest (which indirectly reflects RSA) was largely
      correlated with lactate exchange ability (r=0.55). Our results confirm the
      importance of locomotor- and anaerobic-related variables to RS performance, and
      highlight the importance of disposal of selected metabolic by-products to RSA.

PMID- 25853892
TI  - Apparent time interval of visual stimuli is compressed during fast hand movement.
AB  - The influence of body movements on visual time perception is receiving increased
      attention. Past studies showed apparent expansion of visual time before and after
      the execution of hand movements and apparent compression of visual time during
      the execution of eye movements. Here we examined whether the estimation of sub
      second time intervals between visual events is expanded, compressed, or
      unaffected during the execution of hand movements. The results show that hand
      movements, at least the fast ones, reduced the apparent time interval between
      visual events. A control experiment indicated that the apparent time compression
      was not produced by the participants' involuntary eye movements during the hand
      movements. These results, together with earlier findings, suggest hand movement
      can change apparent visual time either in a compressive way or in an expansive
      way, depending on the relative timing between the hand movement and visual
      stimulus. 

PMID- 25853894
TI  - A Nonclassical Monocyte Phenotype in Peripheral Blood is Associated with
      Nonalcoholic Fatty Liver Disease: A Report from an EMIL Subcohort.
AB  - Nonalcoholic fatty liver disease (NAFLD) as the prototypic hepatic manifestation
      of metabolic syndrome is an independent risk factor for cardiovascular disease.
      Our study was designed to investigate the association between NAFLD and
      alteration in monocyte subsets as hallmark of cardiovascular disease. Seventy
      three "Echinococcus Multilocularis and other medical diseases in Leutkirch"
      (EMIL) population-based cohort participants (mean observation period 11 years)
      were selected to study their monocyte phenotype by multiparameter flow cytometry.
      NAFLD was diagnosed using standard ultrasound based criteria excluding other
      causes of fatty liver disease. Three monocyte subsets ("classical" CD14++ CD16-,
      "intermediate" CD14++  CD16+, "nonclassical" CD14+CD16++  monocytes), and surface
      markers (CD36 and CD9) were determined. Classical risk markers covering
      inflammatory and dysmetabolic characters were also determined. Forty-three out of
      73 subjects revealed a stable clinical phenotype, namely 17 subjects revealed
      NAFLD, whereas 26 subjects showed no fatty liver disease. Compared to the
      nonfatty liver group, the nonclassical monocyte fraction (p=0.049), total
      monocyte fraction and count were increased in NAFLD probands (p=0.028, and 0.035,
      respectively), while classical monocyte fraction (p=0.034) was decreased. Total
      monocyte fraction, nonclassical monocyte fraction, and waist circumstance were
      independent risk factors for NAFLD. The nonclassical monocyte fraction and
      classical monocyte fraction were significantly correlated with waist-to-hip
      ratio. This pilot long-term follow-up study suggests that nonclassical monocyte
      fraction and total monocyte fraction might have potential as a prognostic and
      modifiable biomarker in NFALD patients. This novel marker set might therefore be
      of interest to monitor druggable inflammatory pathways in individuals with
      hepatic manifestation of the metabolic syndrome. 

PMID- 25853895
TI  - Gender development and sexuality in disorders of sex development.
AB  - Understanding psychological development in individuals with disorders of sex
      development (DSD) is important for optimizing their clinical care and for
      identifying paths to competence and health in all individuals. In this paper, we
      focus on psychological outcomes likely to be influenced by processes of physical
      sexual differentiation that may be atypical in DSD, particularly characteristics
      related to being male or female (those that show sex differences in the general
      population, gender identity, and sexuality). We review evidence suggesting that
      (a) early androgens facilitate several aspects of male-typed behavior, with large
      effects on activity interests, and moderate effects on some social and personal
      behaviors (including sexual orientation) and spatial ability; (b) gender
      dysphoria and gender change occur more frequently in individuals with DSD than in
      the general population, with rates varying in relation to syndrome, initial
      gender assignment, and medical treatment; and (c) sexual behavior may be affected
      by DSD through several paths related to the condition and treatment, including
      reduced fertility, physical problems associated with genital ambiguity, social
      stigmatization, and hormonal variations. We also consider limitations to current
      work and challenges to studying gender and sexuality in DSD. We conclude with
      suggestions for a research agenda and a proposed research framework. 

PMID- 25853896
TI  - Promoting Shared Decision Making in Disorders of Sex Development (DSD): Decision
      Aids and Support Tools.
AB  - Specific complaints and grievances from adult patients with disorders of sex
      development (DSD), and their advocates center around the lack of information or
      misinformation they were given about their condition and feeling stigmatized and
      shamed by the secrecy surrounding their condition and its management. Many also
      attribute poor sexual function to damaging genital surgery and/or repeated,
      insensitive genital examinations. These reports suggest the need to reconsider
      the decision-making process for the treatment of children born with DSD. This
      paper proposes that shared decision making, an important concept in adult health
      care, be operationalized for the major decisions commonly encountered in DSD care
      and facilitated through the utilization of decision aids and support tools. This
      approach may help patients and their families make informed decisions that are
      better aligned with their personal values and goals. It may also lead to greater
      confidence in decision making with greater satisfaction and less regret. A brief
      review of the past and current approach to DSD decision making is provided, along
      with a review of shared decision making and decision aids and support tools. A
      case study explores the need and potential utility of this suggested new
      approach. 

PMID- 25853897
TI  - Regioselective Synthesis of Highly Substituted Imidazoles via the Sequential
      Reaction of Allenyl Sulfonamides and Amines.
AB  - A novel synthesis of imidazoles from electron-withdrawing group-substituted
      allenyl sulfonamides with amines was developed. The 4- and 5-functionalized
      imidazoles were constructed regioselectively, which depended on the substituents
      on the nitrogen atoms. 

PMID- 25853898
TI  - Disruption of sphingolipid metabolism augments ceramide-induced autophagy in
      preeclampsia.
AB  - Bioactive sphingolipids including ceramides are involved in a variety of
      pathophysiological processes by regulating cell death and survival. The objective
      of the current study was to examine ceramide metabolism in preeclampsia, a
      serious disorder of pregnancy characterized by oxidative stress, and increased
      trophoblast cell death and autophagy. Maternal circulating and placental ceramide
      levels quantified by tandem mass spectrometry were elevated in pregnancies
      complicated by preeclampsia. Placental ceramides were elevated due to greater de
      novo synthesis via high serine palmitoyltransferase activity and reduced
      lysosomal breakdown via diminished ASAH1 expression caused by TGFB3-induced E2F4
      transcriptional repression. SMPD1 activity was reduced; hence, sphingomyelin
      degradation by SMPD1 did not contribute to elevated ceramide levels in
      preeclampsia. Oxidative stress triggered similar changes in ceramide levels and
      acid hydrolase expression in villous explants and trophoblast cells. MALDI
      imaging mass spectrometry localized the ceramide increases to the trophophoblast
      layers and syncytial knots of placentae from pregnancies complicated by
      preeclampsia. ASAH1 inhibition or ceramide treatment induced autophagy in human
      trophoblast cells via a shift of the BOK-MCL1 rheostat toward prodeath BOK.
      Pharmacological inhibition of ASAH1 activity in pregnant mice resulted in
      increased placental ceramide content, abnormal placentation, reduced fetal
      growth, and increased autophagy via a similar shift in the BOK-MCL1 system. Our
      results reveal that oxidative stress-induced reduction of lysosomal hydrolase
      activities in combination with elevated de novo synthesis leads to ceramide
      overload, resulting in increased trophoblast cell autophagy, and typifies
      preeclampsia as a sphingolipid storage disorder. 

PMID- 25853899
TI  - The paradox of high availability and low recognition of soluble HLA-G by LILRB1
      receptor in rheumatoid arthritis patients.
AB  - HLA-G is a regulatory molecule involved in immunologic tolerance. Growing
      evidence indicates that HLA-G plays a role in the regulation of inflammatory
      processes and autoimmune diseases. This study aimed at a systematic evaluation of
      soluble HLA-G (sHLA-G) in plasma of rheumatoid arthritis (RA) patients with long
      lasting chronic inflammation. RA patients (n=68) and healthy controls (n=26) had
      their plasmatic sHLA-G measured by ELISA whereas the binding capability of sHLA-G
      to its cognate LILRB1 receptor was measured by a Luminex-based assay. All
      subjects were PCR-genotyped for HLA-G 14 bp polymorphism (rs66554220).
      Significantly higher sHLA-G levels were observed in patients (p<0.001), however
      no significant differences were observed in LILRB1 binding capacity between RA
      patients and controls. Remarkably, the proportion of patients presenting specific
      binding of sHLA-G to LILRB1 was significantly decreased as compared to controls
      (56% vs. 81%, p=0.027). Patients without rheumatoid factor (RF-) were
      significantly overrepresented in the group of patients positive for LILRB1
      binding as compared to patients without LILRB1 binding (31% vs 10%, p=0.033).
      Furthermore, methotrexate treated patients (n=58) revealed significantly lower
      LILRB1 binding to sHLA-G molecules than non-treated patients (medians: 12.2 vs.
      67.7 units/ml, p=0.031). Unlike in controls, no significant differences in sHLA-G
      levels were observed among patients grouped by 14 pb genotype. Thus, in a
      substantial number of late RA patients, the circulating sHLA-G molecules are
      impaired regarding LILRB1 recognition, meaning that although increased levels are
      observed; these molecules are not qualified to exert their protective functions
      against inflammation. Our findings offer new insights into the immunopathology of
      RA patients with long-lasting anti-RA-treatment and highlight the importance to
      also measure the binding capability of sHLA-G to LILRB1.

PMID- 25853900
TI  - Effect of vitrification on the microRNA transcriptome in mouse blastocysts.
AB  - Vitrification is commonly used in the cryopreservation of mammalian blastocysts
      to overcome the temporal and spatial limitations of embryo transfer. Previous
      studies have shown that the implantation ability of vitrified blastocysts is
      impaired and that microRNAs (miRNAs) regulate the critical genes for embryo
      implantation. However, little information is available about the effect of
      vitrification on the miRNA transcriptome in blastocysts. In the present study,
      the miRNA transcriptomes in fresh and vitrified mouse blastocysts were analyzed
      by miRNA Taqman assay based method, and the results were validated using
      quantitative real-time PCR (qRT-PCR). Then, the differentially expressed miRNAs
      were assessed using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and
      Genomes (KEGG) databases. Overall, 760 known mouse miRNAs were detected in the
      vitrified and fresh mouse blastocysts. Of these, the expression levels of five
      miRNAs differed significantly: in the vitrified blastocysts, four miRNAs (mmu-miR
      199a-5p, mmu-miR-329-3p, mmu-miR-136-5p and mmu-miR-16-1-3p) were upregulated,
      and one (mmu-miR-212-3p) was downregulated. The expression levels of all miRNAs
      measured by the miRNA Taqman assay based method and qRT-PCR were consistent. The
      four upregulated miRNAs were predicted to regulate 877 candidate target genes,
      and the downregulated miRNA was predicted to regulate 231 genes. The biological
      analysis further showed that the differentially expressed miRNAs mainly regulated
      the implantation of embryos. In conclusion, the results of our study showed that
      vitrification significantly altered the miRNA transcriptome in mouse blastocysts,
      which may decrease the implantation potential of vitrified blastocysts. 

PMID- 25853901
TI  - Impaired functional connectivity within and between frontostriatal circuits and
      its association with compulsive drug use and trait impulsivity in cocaine
      addiction.
AB  - IMPORTANCE: Converging evidence has long identified both impulsivity and
      compulsivity as key psychological constructs in drug addiction. Although
      dysregulated striatal-cortical network interactions have been identified in
      cocaine addiction, the association between these brain networks and addiction is
      poorly understood. OBJECTIVES: To test the hypothesis that cocaine addiction is
      associated with disturbances in striatal-cortical communication as captured by
      resting-state functional connectivity (rsFC), measured from coherent spontaneous
      fluctuations in the blood oxygenation level-dependent functional magnetic
      resonance imaging signal, and to explore the relationships between striatal rsFC,
      trait impulsivity, and uncontrolled drug use in cocaine addiction. DESIGN,
      SETTING, AND PARTICIPANTS: A case-control, cross-sectional study was conducted at
      the National Institute on Drug Abuse Intramural Research Program outpatient
      magnetic resonance imaging facility. Data used in the present study were
      collected between December 8, 2005, and September 30, 2011. Participants included
      56 non-treatment-seeking cocaine users (CUs) (52 with cocaine dependence and 3
      with cocaine abuse) and 56 healthy individuals serving as controls (HCs) matched
      on age, sex, years of education, race, estimated intelligence, and smoking
      status. MAIN OUTCOMES AND MEASURES: Voxelwise statistical parametric analysis
      testing the rsFC strength differences between CUs and HCs in brain regions
      functionally connected to 6 striatal subregions defined a priori. RESULTS:
      Increased rsFC strength was observed predominantly in striatal-frontal circuits;
      decreased rsFC was found between the striatum and cingulate, striatal, temporal,
      hippocampal/amygdalar, and insular regions in the CU group compared with the HCs.
      Increased striatal-dorsal lateral prefrontal cortex connectivity strength was
      positively correlated with the amount of recent cocaine use (uncorrected P <
      .046) and elevated trait impulsivity in the CUs (uncorrected P < .012), and an
      index reflecting the balance between striatal-dorsal anterior cingulate cortex
      and striatal-anterior prefrontal/orbitofrontal cortex circuits was significantly
      associated with loss of control over cocaine use (corrected P < .012).
      CONCLUSIONS AND RELEVANCE: Cocaine addiction is associated with disturbed rsFC in
      several specific striatal-cortical circuits. Specifically, compulsive cocaine
      use, a defining characteristic of dependence, was associated with a balance of
      increased striatal-anterior prefrontal/orbitofrontal and decreased striatal
      dorsal anterior cingulate connectivity; trait impulsivity, both a risk factor for
      and a consequence of cocaine use, was associated with increased dorsal striatal
      dorsal lateral prefrontal cortex connectivity uniquely in CUs. These findings
      provide new insights toward the neurobiological mechanisms of addiction and
      suggest potential novel therapeutic targets for treatment.

PMID- 25853902
TI  - Honey bee workers that are pollen stressed as larvae become poor foragers and
      waggle dancers as adults.
AB  - The negative effects on adult behavior of juvenile undernourishment are well
      documented in vertebrates, but relatively poorly understood in invertebrates. We
      examined the effects of larval nutritional stress on the foraging and recruitment
      behavior of an economically important model invertebrate, the honey bee (Apis
      mellifera). Pollen, which supplies essential nutrients to developing workers, can
      become limited in colonies because of seasonal dearths, loss of foraging habitat,
      or intensive management. However, the functional consequences of being reared by
      pollen-stressed nestmates remain unclear, despite growing concern that poor
      nutrition interacts with other stressors to exacerbate colony decline. We
      manipulated nurse bees' access to pollen and then assessed differences in weight,
      longevity, foraging activity, and waggle-dance behavior of the workers that they
      reared (who were co-fostered as adults). Pollen stress during larval development
      had far-reaching physical and behavioral effects on adult workers. Workers reared
      in pollen-stressed colonies were lighter and shorter lived than nestmates reared
      with adequate access to pollen. Proportionally fewer stressed workers were
      observed foraging and those who did forage started foraging sooner, foraged for
      fewer days, and were more likely to die after only a single day of foraging.
      Pollen-stressed workers were also less likely to waggle dance than their
      unstressed counterparts and, if they danced, the information they conveyed about
      the location of food was less precise. These performance deficits may escalate if
      long-term pollen limitation prevents stressed foragers from providing
      sufficiently for developing workers. Furthermore, the effects of brief pollen
      shortages reported here mirror the effects of other environmental stressors that
      limit worker access to nutrients, suggesting the likelihood of their synergistic
      interaction. Honey bees often experience the level of stress that we created,
      thus our findings underscore the importance of adequate nutrition for supporting
      worker performance and their potential contribution to colony productivity and
      quality pollination services. 

PMID- 25853903
TI  - Role of lipocalin-2 in brain injury after intracerebral hemorrhage.
AB  - Lipocalin-2 (LCN2) is a siderophore-binding protein involved in cellular iron
      transport and neuroinflammation. Both iron and inflammation are involved in brain
      injury after intracerebral hemorrhage (ICH) and this study examined the role of
      LCN2 in such injury. Male adult C57BL/6 wild-type (WT) or LCN2-deficient (LCN2(-/
      )) mice had an intracerebral injection of autologous blood or FeCl2. Control
      animals had a sham operation or saline injection. T2-weighted magnetic resonance
      imaging and behavioral tests were performed at days 1, 3, 7, 14, and 28 after
      injection. In WT mice, brain LCN2 levels were increased in the ipsilateral basal
      ganglia after ICH or iron injection. Lipocalin-2-positive cells were astrocytes,
      microglia, neurons, and endothelial cells. Intracerebral hemorrhage resulted in a
      significant increase in ferritin expression in the ipsilateral basal ganglia.
      Compared with WT mice, ICH caused less ferritin upregulation, microglia
      activation, brain swelling, brain atrophy, and neurologic deficits in LCN2(-/-)
      mice (P<0.05). The size of the lesion induced by FeCl2 injection as well as the
      degree of brain swelling and blood-brain barrier disruption were also less in
      LCN2(-/-) mice (P<0.05). These results suggest a role of LCN2 in enhancing brain
      injury and iron toxicity after ICH. 

PMID- 25853904
TI  - Long-term test-retest reliability of striatal and extrastriatal dopamine D2/3
      receptor binding: study with [(11)C]raclopride and high-resolution PET.
AB  - We measured the long-term test-retest reliability of [(11)C]raclopride binding in
      striatal subregions, the thalamus and the cortex using the bolus-plus-infusion
      method and a high-resolution positron emission scanner. Seven healthy male
      volunteers underwent two positron emission tomography (PET) [(11)C]raclopride
      assessments, with a 5-week retest interval. D2/3 receptor availability was
      quantified as binding potential using the simplified reference tissue model.
      Absolute variability (VAR) and intraclass correlation coefficient (ICC) values
      indicated very good reproducibility for the striatum and were 4.5%/0.82,
      3.9%/0.83, and 3.9%/0.82, for the caudate nucleus, putamen, and ventral striatum,
      respectively. Thalamic reliability was also very good, with VAR of 3.7% and ICC
      of 0.92. Test-retest data for cortical areas showed good to moderate
      reproducibility (6.1% to 13.1%). Our results are in line with previous test
      retest studies of [(11)C]raclopride binding in the striatum. A novel finding is
      the relatively low variability of [(11)C]raclopride binding, providing suggestive
      evidence that extrastriatal D2/3 binding can be studied in vivo with
      [(11)C]raclopride PET to be verified in future studies. 

PMID- 25853905
TI  - Intraventricular fibrinolysis with tissue plasminogen activator is associated
      with transient cerebrospinal fluid inflammation: a randomized controlled trial.
AB  - Locally administered tissue plasminogen activator (TPA) accelerates clearance of
      intraventricular hemorrhage (IVH), but its impact on neurologic outcomes remains
      unclear and preclinical research suggests it may have pro-inflammatory effects.
      We randomly allocated patients with ruptured cerebral aneurysms and IVH, treated
      with endovascular coiling and ventricular drainage, to receive either 2-mg
      intraventricular TPA or placebo every 12 hours. Cerebrospinal fluid (CSF) and
      serum cytokine and white blood cell (WBC) concentrations were measured before
      drug administration and daily for 72 hours. Cerebrospinal fluid D-dimer levels
      were assessed 6 and 12 hours after administration to quantify fibrinolysis. Six
      patients were randomized to each group. Patients treated with TPA developed
      higher CSF cytokine concentrations compared with placebo-treated patients (P<0.05
      for tumor necrosis factor-alpha, interferon-gamma, interleukin (IL)-1alpha, IL
      1beta, IL-2, IL-4, and IL-6), as well as higher CSF WBC counts (P=0.03).
      Differences were greatest after 24 hours and decreased over 48 to 72 hours. The
      magnitude of the inflammatory response was significantly associated with peak CSF
      D-dimer concentration and extent of IVH clearance. We conclude that
      intraventricular TPA administration produces a transient local inflammatory
      response, the severity of which is strongly associated with the degree of
      fibrinolysis, suggesting it may be induced by release of hematoma breakdown
      products, rather than the drug itself.

PMID- 25853906
TI  - Amyloid beta 1-42 induces hypometabolism in human stem cell-derived neuron and
      astrocyte networks.
AB  - Alzheimer's disease (AD) is the most common form of dementia, affecting more than
      35 million people worldwide. Brain hypometabolism is a major feature of AD,
      appearing decades before cognitive decline and pathologic lesions. To date, the
      majority of studies on hypometabolism in AD have used transgenic animal models or
      imaging studies of the human brain. As it is almost impossible to validate these
      findings using human tissue, alternative models are required. In this study, we
      show that human stem cell-derived neuron and astrocyte cultures treated with
      oligomers of amyloid beta 1-42 (Abeta1-42) also display a clear hypometabolism,
      particularly with regard to utilization of substrates such as glucose, pyruvate,
      lactate, and glutamate. In addition, a significant increase in the glycogen
      content of cells was also observed. These changes were accompanied by changes in
      NAD(+)/NADH, ATP, and glutathione levels, suggesting a disruption in the energy
      redox axis within these cultures. The high energy demands associated with
      neuronal functions such as memory formation and protection from oxidative stress
      put these cells at particular risk from Abeta-induced hypometabolism. Further
      research using this model may elucidate the mechanisms associated with Abeta
      induced hypometabolism. 

PMID- 25853907
TI  - Perturbations of the cerebrovascular  matrisome: A convergent mechanism in  small
      vessel disease of the brain?
AB  - The term matrisome refers to the ensemble of proteins constituting the
      extracellular matrix (ECM) (core matrisome) as well as the proteins associated
      with the ECM. Every organ has an ECM with a unique composition that not only
      provides the support and anchorage for cells, but also controls fundamental
      cellular processes as diverse as differentiation, survival, proliferation, and
      polarity. The current knowledge of the matrisome of small brain vessels is
      reviewed with a focus on the basement membrane (BM), a specialized form of ECM
      located at the interface between endothelial cells, contractile cells (smooth
      muscle cells and pericytes), and astrocyte endfeet-a very strategic location in
      the communication pathway between the cerebral microcirculation and astrocytes.
      We discuss some of the most recent genetic data and relevant findings from
      experimental models of nonamyloid cerebral small vessel disease (SVD). We propose
      the concept that perturbations of the cerebrovascular matrisome is a convergent
      pathologic pathway in monogenic forms of SVD, and is likely relevant to the
      sporadic disease.

PMID- 25853908
TI  - Chronic cerebral hypoperfusion induces vascular plasticity and hemodynamics but
      also neuronal degeneration and cognitive impairment.
AB  - Chronic cerebral hypoperfusion (CCH) induces cognitive impairment, but the
      compensative mechanism of cerebral blood flow (CBF) is not fully understood. The
      present study mainly investigated dynamic changes in CBF, angiogenesis, and
      cellular pathology in the cortex, the striatum, and the cerebellum, and also
      studied cognitive impairment of rats induced by bilateral common carotid artery
      occlusion (BCCAO). Magnetic resonance imaging (MRI) techniques, immunochemistry,
      and Morris water maze were employed to the study. The CBF of the cortex,
      striatum, and cerebellum dramatically decreased after right common carotid artery
      occlusion (RCCAO), and remained lower level at 2 weeks after BCCAO. It returned
      to the sham level from 3 to 6 weeks companied by the dilation of vertebral
      arteries after BCCAO. The number of microvessels declined at 2, 3, and 4 weeks
      but increased at 6 weeks after BCCAO. Neuronal degeneration occurred in the
      cortex and striatum from 2 to 6 weeks, but the number of glial cells dramatically
      increased at 4 weeks after BCCAO. Cognitive impairment of ischemic rats was
      directly related to ischemic duration. Our results suggest that CCH induces a
      compensative mechanism attempting to maintain optimal CBF to the brain. However,
      this limited compensation cannot prevent neuronal loss and cognitive impairment
      after permanent ischemia. 

PMID- 25853910
TI  - Diverse functions of pericytes in cerebral blood flow regulation and ischemia.
AB  - Pericytes are mural cells with contractile properties. Here, we provide evidence
      that microvascular pericytes modulate cerebral blood flow in response to neuronal
      activity ('functional hyperemia'). Besides their role in neurovascular coupling,
      pericytes are responsive to brain damage. Cerebral ischemia is associated with
      constrictions and death of capillary pericytes, followed by fibrotic
      reorganization of the ischemic tissue. The data suggest that precapillary
      arterioles and capillaries are major sites of hemodynamic regulation in the
      brain. 

PMID- 25853909
TI  - Tibial fracture exacerbates traumatic brain injury outcomes and neuroinflammation
      in a novel mouse model of multitrauma.
AB  - Multitrauma is a common medical problem worldwide, and often involves concurrent
      traumatic brain injury (TBI) and bone fracture. Despite the high incidence of
      combined TBI and fracture, preclinical TBI research commonly employs independent
      injury models that fail to incorporate the pathophysiologic interactions
      occurring in multitrauma. Here, we developed a novel mouse model of multitrauma,
      and investigated whether bone fracture worsened TBI outcomes. Male mice were
      assigned into four groups: sham-TBI+sham-fracture (SHAM); sham-TBI+fracture (FX);
      TBI+sham-fracture (TBI); and TBI+fracture (MULTI). The injury methods included a
      closed-skull weight-drop TBI model and a closed tibial fracture. After a 35-day
      recovery, mice underwent behavioral testing and magnetic resonance imaging (MRI).
      MULTI mice displayed abnormal behaviors in the open-field compared with all other
      groups. On MRI, MULTI mice had enlarged ventricles and diffusion abnormalities
      compared with all other groups. These changes occurred in the presence of
      heightened neuroinflammation in MULTI mice at 24 hours and 35 days after injury,
      and elevated edema and blood-brain barrier disruption at 24 hours after injury.
      Together, these findings indicate that tibial fracture worsens TBI outcomes, and
      that exacerbated neuroinflammation may be an important factor that contributes to
      these effects, which warrants further investigation.

PMID- 25853912
TI  - Words and Patterns That Comprise Resistance Training Exercise Names.
AB  - Nuzzo, JL. Words and patterns that comprise resistance training exercise names. J
      Strength Cond Res 31(3): 826-830, 2017-Limited research exists on the language
      associated with resistance training. The purpose of this study was to identify
      the ways in which resistance training exercises are named. Names of 57 exercises
      were obtained from the National Strength and Conditioning Association's Exercise
      Technique Manual for Resistance Training. The analysis consisted of categorizing
      into themes all the words of the exercise names and then identifying naming
      patterns. Names of the 57 exercises were comprised 188 total words. Seven percent
      of the words described body position (e.g., "seated"), 1.1% described body
      position direction (e.g., "over"), 19.1% described a body part (e.g.,
      "shoulder"), 1.1% were body part adjectives ("stiff"), 30.3% described action
      (e.g., "row"), 5.9% described action direction (e.g., "lateral"), 23.4% described
      equipment (e.g., "barbell"), 8% described equipment position (e.g., "incline"),
      and 4.3% were considered miscellaneous (e.g., "power"). Of the 57 exercise names,
      22.8% contained a body position word, 3.5% contained a body position direction
      word, 54.4% contained a body part word, 3.5% contained a body part adjective
      word, 94.7% contained an action word, 19.3% contained an action direction word,
      61.4% contained an equipment word, 26.3% contained an equipment position word,
      and 12.3% contained a miscellaneous word. These types of words were used
      inconsistently. Additionally, 35 different naming patterns were discovered among
      the 57 exercise names. Overall, the findings reveal that current strategies for
      naming exercises are inconsistent. The strength and conditioning field can use
      this information to move toward standardizing the way in which resistance
      training exercises are named.

PMID- 25853911
TI  - Expression of the ALS-causing variant hSOD1(G93A) leads to an impaired integrity
      and altered regulation of claudin-5 expression in an in vitro blood-spinal cord
      barrier model.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder
      characterized by progressive paralysis due to the loss of primary and secondary
      motor neurons. Mutations in the Cu/Zn-superoxide dismutase (SOD1) gene are
      associated with familial ALS and to date numerous hypotheses for ALS pathology
      exist including impairment of the blood-spinal cord barrier. In transgenic mice
      carrying mutated SOD1 genes, a disrupted blood-spinal cord barrier as well as
      decreased levels of tight junction (TJ) proteins ZO-1, occludin, and claudin-5
      were detected. Here, we examined TJ protein levels and barrier function of
      primary blood-spinal cord barrier endothelial cells of presymptomatic hSOD1(G93A)
      mice and bEnd.3 cells stably expressing hSOD1(G93A). In both cellular systems, we
      observed reduced claudin-5 levels and a decreased transendothelial resistance
      (TER) as well as an increased apparent permeability. Analysis of the beta
      catenin/AKT/forkhead box protein O1 (FoxO1) pathway and the FoxO1-regulated
      activity of the claudin-5 promoter revealed a repression of the claudin-5 gene
      expression in hSOD1(G93A) cells, which was depended on the phosphorylation status
      of FoxO1. These results strongly indicate that mutated SOD1 affects the
      expression and localization of TJ proteins leading to impaired integrity and
      breakdown of the blood-spinal cord barrier. 

PMID- 25853913
TI  - Contributing Factors to Change-of-Direction Ability in Professional Rugby League
      Players.
AB  - Rugby league is an intermittent team sport in which players are regularly
      required to accelerate, decelerate, and change direction rapidly. This study
      aimed to determine the contributing factors to change-of-direction (COD) ability
      in professional rugby league players and to validate the physical and
      physiological components of a previously proposed COD ability predictor model.
      Thirty-one male professional rugby league players (age: 24.3 +/- 4.4 years;
      height: 1.83 +/- 0.06 m; body mass: 98.1 +/- 9.8 kg) were assessed for
      anthropometry, linear speed, various leg muscle qualities, and COD ability.
      Change-of-direction ability was assessed for both the dominant (D) and
      nondominant (ND) legs using the 505 test. Stepwise multiple regression analyses
      determined the combined effect of the physical and physiological variables on COD
      ability. Maximal linear speed (SpMax) and relative squat strength (squat:BM)
      explained 61% of the variance in 505-D performance, whereas measures of mass,
      unilateral, and bilateral power contributed 67% to 505-ND performance. These
      results suggest that the 505-ND task was heavily dependent on relative strength
      and power, whereas the 505-D task was best predicted by linear sprint speed.
      Second, the physical component of the COD predictor model demonstrated poor
      correlations (r = -0.1 to -0.5) between absolute strength and power measures and
      COD ability. When made relative to body mass, strength and power measures and COD
      ability shared stronger relationships (r = -0.3 to -0.7). Change-of-direction
      ability in professional rugby league players would be best improved through
      increases in an athlete's strength and power while maintaining lean muscle mass.

PMID- 25853914
TI  - Effects of Low- vs. High-Load Resistance Training on Muscle Strength and
      Hypertrophy in Well-Trained Men.
AB  - The purpose of this study was to compare the effect of low- versus high-load
      resistance training (RT) on muscular adaptations in well-trained subjects.
      Eighteen young men experienced in RT were matched according to baseline strength
      and then randomly assigned to 1 of 2 experimental groups: a low-load RT routine
      (LL) where 25-35 repetitions were performed per set per exercise (n = 9) or a
      high-load RT routine (HL) where 8-12 repetitions were performed per set per
      exercise (n = 9). During each session, subjects in both groups performed 3 sets
      of 7 different exercises representing all major muscles. Training was performed 3
      times per week on nonconsecutive days, for a total of 8 weeks. Both HL and LL
      conditions produced significant increases in thickness of the elbow flexors (5.3
      vs. 8.6%, respectively), elbow extensors (6.0 vs. 5.2%, respectively), and
      quadriceps femoris (9.3 vs. 9.5%, respectively), with no significant differences
      noted between groups. Improvements in back squat strength were significantly
      greater for HL compared with LL (19.6 vs. 8.8%, respectively), and there was a
      trend for greater increases in 1 repetition maximum (1RM) bench press (6.5 vs.
      2.0%, respectively). Upper body muscle endurance (assessed by the bench press at
      50% 1RM to failure) improved to a greater extent in LL compared with HL (16.6 vs.
      -1.2%, respectively). These findings indicate that both HL and LL training to
      failure can elicit significant increases in muscle hypertrophy among well-trained
      young men; however, HL training is superior for maximizing strength adaptations.

PMID- 25853915
TI  - Influence of Different Work and Rest Distributions on Performance and Fatigue
      During Simulated Team Handball Match Play.
AB  - This study investigated the effect of different interchange strategies on
      performance and pacing strategy during a simulated team-sport protocol. Eight
      youth male team handball players completed 2 conditions (LONG-work: 3 * 13:00
      minutes, rest: 8:00 minutes; SHORT-work: 5 * 7:48 minutes, rest: 3:45 minutes).
      Participants were tested for 20-m sprint, countermovement jump, throwing
      performance, and heart rate (HR) during conditions. Postcondition measures
      included repeated shuttle-sprint and jump ability, session rating of perceived
      exertion, blood lactate, and glucose. Faster sprint (3.87 +/- 0.27 seconds cf.
      3.97 +/- 0.24 seconds, effect size [ES] = 0.39, p = 0.03) and throwing
      performance (70.02 +/- 7.40 km.h(-1) cf. 69.04 +/- 5.57 km.h(-1), p > 0.05, ES = 
      0.15) occurred in SHORT compared with LONG by a "likely small" difference. Higher
      summated HR (157 +/- 21 cf. 150 +/- 15 AU) occurred in SHORT compared with LONG
      by a "likely small" difference (ES = 0.37, p > 0.05). SHORT resulted in lower
      session rating of perceived exertion (224 +/- 45 AU cf. 282 +/- 35 AU, ES = 1.45,
      p = 0.001) and higher blood glucose (6.06 +/- 0.69 mmol.l(-1) cf. 4.98 +/- 1.10
      mmol.l(-1), ES = -1.17, p = 0.03) by a "most likely moderate" difference compared
      with LONG. Repeated shuttle sprint was better preserved after SHORT, with
      "moderately lower" 10 and 25 m times (p <= 0.05). Interchange strategies using
      SHORT rather than LONG work and rest periods result in lower physiological load,
      leading to improved fatigue resistance and better preservation of high-intensity
      movements during matches.

PMID- 25853916
TI  - Placebo Effect: Influence on Repeated Intermittent Sprint Performance on
      Consecutive Days.
AB  - Despite the available literature addressing the placebo effect's role in
      mediating human performance, there is a paucity of research addressing the
      possibility of a placebo effect both within and between bouts of repeated sprint
      performance on consecutive days. Therefore, the purpose of this study was to
      determine whether the administration of a placebo influences recovery during
      sessions of intermittent sprinting. Ten subjects performed 4 repeated sprint
      tests under 2 different conditions; 2 while being administered a control beverage
      separated by 24 hours of recovery and the other 2 with a placebo beverage
      separated by 24 hours of recovery. Before each sprint test, subjects provided
      perceived recovery status (PRS). Ratings of perceived exertion were recorded
      within 5 seconds after each sprint. After each repeated sprint protocol, subjects
      were asked to provide a rating of perceived exertion (RPE), rate their pain, and
      provided a blood lactate sample. Power was recorded throughout each session from
      a nonmotorized treadmill to analyze changes in sprinting performance. Repeated
      measures analysis of variance was used to determine significant differences in
      peak and mean power, PRS, RPE, pain, and blood lactate. The placebo trial
      produced significantly higher peak (p < 0.001) and mean power (p = 0.002) vs. the
      control in later sprints absent of any other significant difference in metabolic
      or perceptual strain (p > 0.05). In conclusion, it seems that the administration
      of a placebo can attenuate the decline in performance as fatigue increases during
      repeated sprinting bouts.

PMID- 25853917
TI  - Muscle Activity During Unilateral vs. Bilateral Battle Rope Exercises.
AB  - High training intensity is important for efficient strength gains. Although
      battle rope training is metabolically demanding, no studies have quantified
      intensity of muscle activity during this type of training. This study analyzes
      muscle activity during unilateral alternating waves vs. bilateral waves of battle
      rope training. Twenty-one volunteers participated in a repeated-measures study on
      2 different occasions. Surface electromyographic signals were recorded from the
      anterior deltoid (AD), external oblique (OBLIQ), lumbar erector spinae (LUMB),
      and gluteus medius (GM) during bilateral waves and unilateral waves and were
      normalized to the maximum voluntary isometric contraction (MVIC). Results showed
      that muscle activity ranged from 51%MVIC to 73%MVIC for AD, OBLIQ, and LUMB,
      whereas GM muscle activity was only 14-18%MVIC. OBLIQ activation was
      significantly greater (20%MVIC; p = 0.02) with the unilateral waves compared with
      the bilateral waves, whereas LUMB signal was significantly higher (16%MVIC; p =
      0.001) with the bilateral waves compared with the unilateral waves. In
      conclusion, both wave movements can be used to provide moderate to high levels of
      muscle activity in the AD, OBLIQ, and LUMB. Fitness practitioners aiming for
      higher OBLIQ activity should perform unilateral waves, whereas the bilateral
      variation of the movement can be used for higher LUMB activity.

PMID- 25853918
TI  - Functional Movement Screen for Predicting Running Injuries in 18- to 24-Year-Old
      Competitive Male Runners.
AB  - The purpose of this study was to investigate whether the functional movement
      screen (FMS) could predict running injuries in competitive runners. Eighty-four
      competitive male runners (average age = 20.0 +/- 1.1 years) participated. Each
      subject performed the FMS, which consisted of 7 movement tests (each score range:
      0-3, total score range: 0-21), during the preseason. The incidence of running
      injuries (time lost because of injury <= 4 weeks) was investigated through a
      follow-up survey during the 6-month season. Mann-Whitney U-tests were used to
      investigate which movement tests were significantly associated with running
      injuries. The receiver-operator characteristic (ROC) analysis was used to
      determine the cutoff. The mean FMS composite score was 14.1 +/- 2.3. The ROC
      analysis determined the cutoff at 14/15 (sensitivity = 0.73, specificity = 0.54),
      suggesting that the composite score had a low predictability for running
      injuries. However, the total scores (0-6) from the deep squat (DS) and active
      straight leg raise (ASLR) tests (DS and ASLR), which were significant with the U
      test, had relatively high predictability at the cutoff of 3/4 (sensitivity =
      0.73, specificity = 0.74). Furthermore, the multivariate logistic regression
      analysis revealed that the DS and ASLR scores of <=3 significantly influenced the
      incidence of running injuries after adjusting for subjects' characteristics (odds
      ratio = 9.7, 95% confidence interval = 2.1-44.4). Thus, the current study
      identified the DS and ASLR score as a more effective method than the composite
      score to screen the risk of running injuries in competitive male runners.

PMID- 25853920
TI  - Muscle Damage Response in Female Collegiate Athletes After Repeated Sprint
      Activity.
AB  - Exercise-induced muscle damage (EIMD) is a well-investigated area, however there
      is a paucity of data surrounding the damage response in females. The aim of this
      study was to examine the damage responses from a sport-specific bout of repeated
      sprints in female athletes. Eleven well-trained females (mean +/- SD; age: 22 +/-
      3 years; height: 166.6 +/- 5.7 cm; mass: 62.7 +/- 4.5 kg) in the luteal phase of
      the menstrual cycle completed a repeated sprint protocol designed to induce EIMD
      (15 * 30 m sprints). Creatine kinase, countermovement jump height, knee extensor
      maximal voluntary isometric contraction (MVIC) force, delayed onset muscle
      soreness (DOMS), 30-m sprint time, and limb girth were recorded before, after,
      24, 48, and 72 hours after exercise. Creatine kinase was elevated at 24, 48, and
      72 hours (p <= 0.05), peaking at 24 hours (+418%) and returning toward baseline
      at 72 hours. Countermovement jump height was reduced immediately after, 24, and
      48 hours (p <= 0.05). Sprint performance was also negatively affected immediately
      after, 24, 48, and 72 hours after exercise. Muscle soreness peaked at 48 hours (p
      < 0.01) and remained significantly elevated at 72 hours after exercise (p <
      0.01). Limb girth and MVIC did not alter over time. This study provides new
      information on the EIMD response in trained females after a sport-specific bout
      of repeated sprints. Importantly, this damage response has the potential to
      negatively affect performance for several days after exercise.

PMID- 25853921
TI  - Absolute Bronsted Acidities and pH Scales in Ionic Liquids.
AB  - Although receiving large interest over the last years, some fundamental aspects
      of Bronsted acidity in ionic liquids (ILs) have up to now been insufficiently
      highlighted. In this work, standard states, activity, and activity coefficient
      definitions for IL solvent systems were developed from general thermodynamic
      considerations and then extended to a general mixed solvent standard state. By
      using the bromide/bromoaluminate systems as representative ILs, formulae for
      thermodynamically consistent pH scales for ILs with simple (Br(-) ) and complex
      ([Aln Br3n+1 ](-) ) anions were derived on the basis of the chemical potential of
      the proton. Supported by quantum chemical [ccsd(t)/MP2/DFT/COSMO-RS]
      calculations, Gibbs solvation energies of the proton were calculated, which
      allowed the ILs to be ranked in absolute acidity, that is, pHabs or MUabs (H(+) ,
      IL), and additionally allowed their acidity to be compared with molecular
      Bronsted acid systems. It was shown that bromoaluminate ILs are suited for
      reaching superacidic conditions. The complexity of autoprotolysis processes in C6
      MIM(+) [AlBr4 ](-) (C6 MIM=1-hexyl-3-methylimidazolium) with or without the
      addition of basic (i.e. Br(-) ) or acidic (AlBr3 and/or HBr) solutes was examined
      in detail by model calculations, and they indicated a large thermodynamic
      influence of small deviations from the exact stoichiometric composition. 

PMID- 25853922
TI  - Influence of CYP2D6 and CYP3A4 Phenotypes, Drug Interactions, and Vitamin D
      Status on Tamoxifen Biotransformation.
AB  - OBJECTIVE: In view of the large variability on therapeutic response and the
      multiple factors associated to tamoxifen (TAM) metabolic activation, this study
      aimed to evaluate the effect of CYP2D6 and CYP3A4 phenotypes, drug interactions,
      and vitamin D exposure on TAM metabolism in a group of breast cancer patients.
      METHODS: Trough blood samples were collected from 116 patients. TAM and
      metabolites endoxifen (EDF), N-desmethyltamoxifen, and 4-hydroxytamoxifen (HTF)
      were measured in plasma by liquid chromatography-tandem mass spectrometry. CYP2D6
      and CYP3A4 phenotyping were obtained according to
      [dextromethorphan]/[dextrorphan] and [omeprazole]/[omeprazole sulfone] metabolic
      ratios, measured by high-performance liquid chromatography in plasma collected 3
      hours after oral administration of 33 mg of dextromethorphan and 20 mg of
      omeprazole. Vitamin D3 was measured in plasma by high-performance liquid
      chromatography-ultraviolet. Data on concomitant use of drug considered as CYP2D6
      and CYP3A4 inhibitor or inducer and vitamin D supplementation were recorded.
      RESULTS: About 20% of patients had reduced CYP2D6 metabolic activity and 7%
      CYP3A4 impaired metabolism. EDF levels diminished proportionally to the reduction
      of CYP2D6 metabolic activity (poor metabolizer 2.79 ng.mL, intermediate
      metabolizer (IM) 5.36 ng.mL, and extensive metabolizer 10.65 ng.mL, P < 0.01).
      Median plasma levels of TAM (161.50 ng.mL) and HTF (1.32 ng.mL) in CYP2D6
      IM/CYP3A4 poor metabolizer patients were higher (P < 0.05) than those from CYP2D6
      IM/CYP3A4 extensive metabolizer patients (122.07 ng.mL and 0.61 ng.mL,
      respectively). Seasons contributed to the interpatient variability of EDF and HTF
      levels; summer concentrations were 24% and 42% higher compared with winter.
      Vitamin D3 was not associated to CYP3A4 metabolic activity, indicating that other
      mechanisms might be involved in the relation between TAM metabolism and vitamin D
      exposure. CONCLUSIONS: CYP3A4 contributes to the bioactivation of TAM through
      formation of HTF and becomes increasingly important in case of reduced or absent
      CYP2D6 activity. EDF and HTF exposure were associated to seasonal variations,
      with considerable higher plasma concentrations during summer.

PMID- 25853923
TI  - Routinely Established Skewed Thiopurine Metabolism Leads to a Strikingly High
      Rate of Early Therapeutic Failure in Patients With Inflammatory Bowel Disease.
AB  - BACKGROUND: The conventional thiopurines azathioprine and mercaptopurine are
      considered maintenance immunosuppressive drugs of choice in the treatment of
      inflammatory bowel disease (IBD). Unfortunately, treatment is often discontinued
      because of adverse events (AEs) or refractoriness, retrospectively associated
      with the high levels of the thiopurine metabolites 6-methylmercaptopurine
      ribonucleotides (6-MMPR). Patients with a clinically "skewed" thiopurine
      metabolism may be particularly at risk for therapy failure. We determined the
      predictive value of this pharmacological phenomenon in patients with IBD during
      regular thiopurine therapy. METHODS: Clinical effectiveness and tolerability of
      weight-based thiopurine therapy were determined in all patients with IBD
      displaying a skewed metabolism [ratio 6-MMPR/6-thioguanine nucleotide (6-TGN)
      >20]. All samples were routinely assessed between 2008 and 2012, as part of
      standard clinical follow-up after initiation of conventional thiopurine therapy.
      RESULTS: Forty-one (84%) of 49 included patients with IBD discontinued
      thiopurines (55% female, 53% with Crohn disease) with a median duration of 14
      weeks (range, 7-155). The majority of patients with a skewed metabolism
      discontinued thiopurines because of adverse events (55%) or refractoriness (12%).
      The most commonly observed adverse event was hepatotoxicity (18 patients, 37%).
      Median 6-TGN level was 159 pmol/8 * 10 RBC (range, 46-419), median 6-MMPR level
      was 11,020 pmol/8 * 10 RBC (range, 3610-43,670), and the median 6-MMPR/6-TGN
      ratio was 72 (range, 29-367). Thiopurine therapy failure was associated with a
      ratio above 50 (P < 0.03). Hepatotoxicity occurred more frequently in patients
      with an extremely skewed metabolism (6-MMPR/6-TGN ratio >100) (P < 0.01).
      CONCLUSIONS: This study demonstrates that a routinely established skewed
      metabolism is a major risk factor for future thiopurine failure in patients with
      IBD. These observations imply that routine thiopurine metabolite measurements may
      be used as a prognostic tool to identify those patients with an aberrant-skewed
      metabolism at an early stage, possibly benefitting from therapy adjustments.

PMID- 25853924
TI  - Gradient-index materials based on thiol-ene networks.
AB  - Gradient-index (GRIN) optics offer spatially varied refractive indexes that can
      enhance current imaging technologies. Current methods to fabricate GRIN optics
      are highly complex and costly. Here we report a simple and efficient method that
      utilizes commercially available reagents to fabricate polymeric GRIN optics with
      significant refractive index differences (Deltan = 0.04). First, two different
      mixtures of network precursors are layered and time allotted for molecular
      diffusion in the liquid state, prior to curing. The resulting, partially mixed
      layers are UV-cured to yield clear, glassy molecular networks with fixed
      refractive index gradients. The fully cured network resins exhibit smoothly
      varying composition and refractive index over centimeter length scales, confirmed
      by spectroscopy and interferometry. 

PMID- 25853925
TI  - Sulfur dioxide exposure and other factors affecting age at natural menopause in
      the Jinchuan cohort.
AB  - OBJECTIVE: To describe the associations between occupational exposures and age at
      natural menopause in the Jinchuan cohort. METHODS: The Jinchuan cohort consists
      of all current or retired workers of the Jinchuan Nonferrous Metals Corporation
      (JNMC) in Jinchang, Gansu, China. Our final study population consisted of 3167
      postmenopausal women. The data used for this study were derived from the
      epidemiological survey and were self-reported. Age at natural menopause (ANM) was
      defined as the age at the last period prior to 12 months of amenorrhea in women
      who experienced natural menopause. ANM was related to five commonly reported
      occupational exposures using bivariate and multivariate Cox proportional hazards
      regressions. RESULTS: Blue-collar workers have significantly earlier mean ANM
      (49.0 years) than white-collar workers (49.5 years). Sulfur dioxide exposure was
      found to be associated with earlier mean ANM in blue-collar workers. After
      stratifying both blue-collar workers and white-collar workers further by exposure
      time for each of the exposures, blue-collar workers exposed to sulfur dioxide for
      21-25 years had the earliest mean ANM (47.8 years) of any level of any exposure
      in this study. CONCLUSION: This paper is significant because it is the first
      report of an association between sulfur dioxide and menopause, and one of few
      papers to look at the determinants of ANM in an occupational cohort. Blue-collar
      workers had earlier mean ANM than white-collar workers. Blue-collar workers are
      more exposed to sulfur dioxide and other occupational exposures than white-collar
      workers, and blue-collar workers who are more exposed to sulfur dioxide have
      earlier menopause. Sulfur dioxide may be part of the reason that blue-collar
      workers experience earlier menopause than white-collar workers.

PMID- 25853926
TI  - Phosphor informatics based on confirmatory factor analysis.
AB  - The theoretical understanding of phosphor luminescence is far from complete. To
      accomplish a full understanding of phosphor luminescence, the data mining of
      existing experimental data should receive equal consideration along with
      theoretical approaches. We mined the crystallographic and luminescence data of 75
      reported Eu(2+)-doped phosphors with a single Wyckoff site for Eu(2+) activator
      accommodation, and 32 descriptors were extracted. A confirmatory factor analysis
      (CFA) based on a structural equation model (SEM) was employed since it has been
      helpful in understanding complex problems in social sciences and in
      bioinformatics. This first attempt at applying CFA to the data mining of
      engineering materials provided a better understanding of the structural and
      luminescent-property relationships for LED phosphors than what we have learnt so
      far from the conventional theoretical approaches. 

PMID- 25853927
TI  - Creating high quality Ca:TiO2-B (CaTi5O11) and TiO2-B epitaxial thin films by
      pulsed laser deposition.
AB  - We demonstrate, in great detail, a completely waterless synthesis route to
      produce highly crystalline epitaxial thin films of TiO2-B and its more stable
      variant CaTi5O11, using pulsed laser deposition (PLD). 

PMID- 25853928
TI  - Cochrane review summary: Interventions to increase influenza vaccination rates of
      those 60 years and older in the community.

PMID- 25853929
TI  - Biodegradable biliary stent in the endoscopic treatment of cystic duct leak after
      cholecystectomy: the first case report and review of literature.
AB  - BACKGROUND: The preferred therapy for simple postcholecystectomy biliary leak
      consists of percutaneous drainage and biliary stent insertion under endoscopic
      retrograde cholangiopancreatography (ERCP). With a novel endoscopic insertion
      device, a biodegradable biliary stent (BDBS) may be used in the treatment of a
      cystic duct leak without repeated endoscopy for stent removal. The objective of
      this article was to report the first case of endoscopic insertion of BDBS for
      postoperative bile leak and assess its feasibility and safety. PATIENT AND
      METHODS: A 64-year-old man with a postoperative leak from the cystic duct stump
      was treated with ERCP, biliary sphincterotomy, and insertion of a self-expandable
      40- * 8-mm polydixanone BDBS (Ella CS, Hradec Kralove, Czech Republic) after
      insertion of a percutaneous drain. RESULTS: Endoscopic insertion of BDBS was
      successful and uncomplicated. On Day 7 after ERCP, the patient was in good
      condition, no signs of bile leak or inflammation were observed, and the
      percutaneous drain was removed. At 3 months, magnetic resonance imaging showed
      that the BDBS was patent and in the right location. At 6 months, the stent had
      expectedly degraded. CONCLUSIONS: A novel endoscopic insertion device with a
      polydixanone BDBS appears feasible in treating disorders of the human biliary
      duct. BDBS now offers an encouraging option for endoscopic therapy of bile leaks.

PMID- 25853931
TI  - Increasing efficiency, speed, and responsivity of vanadium dioxide based
      photothermally driven actuators using single-wall carbon nanotube thin-films.
AB  - Vanadium dioxide (VO2)-based actuators have demonstrated great performance in
      terms of strain energy density, speed, reversible actuation, programming
      capabilities, and large deflection. The relative low phase transition temperature
      of VO2 (~68  degrees C) gives this technology an additional advantage over
      typical thermal actuators in terms of power consumption. However, this advantage
      can be further improved if light absorption is enhanced. Here we report a VO2
      based actuator technology that incorporates single-wall carbon nanotubes (SWNTs)
      as an effective light absorber to reduce the amount of photothermal energy
      required for actuation. It is demonstrated that the chemistry involved in the
      process of integrating the SWNT film with the VO2-based actuators does not alter
      the quality of the VO2 film, and that the addition of such film enhances the
      actuator performance in terms of speed and responsivity. More importantly, the
      results show that the combination of VO2 and SWNT thin films is an effective
      approach to increase the photothermal efficiency of VO2-based actuators. The
      integration of SWNT films in VO2 devices can be easily applied to other VO2-based
      phototransducers as well as to similar devices based on other phase-change
      materials. While adding a sufficiently thick layer of some arbitrary material
      with high absorption for the light used for actuation (lambda = 650 nm wavelength
      in this case) could have improved conversion of light to heat in the device, it
      could also have impeded actuation by increasing its stiffness. It is noted,
      however, that the low effective Young's modulus of SWNT film coating used in this
      work does not impair the actuation range. 

PMID- 25853930
TI  - Labour productivity losses caused by premature death associated with hepatitis C
      in Spain.
AB  - BACKGROUND AND AIMS: Hepatitis C virus (HCV) infection places a huge burden on
      healthcare systems. There is no study assessing the impact of HCV infection on
      premature deaths in Spain. The aim of this study was to estimate productivity
      losses because of premature deaths attributable to hepatitis C occurring in Spain
      during 2007-2011. MATERIALS AND METHODS: We use data from several sources
      (Registry of Deaths, Labour Force Survey and Wage Structure Survey) to develop a
      simulation model based on the human capital approach and to estimate the flows in
      labour productivity losses in the period considered. The attributable fraction
      method was used to estimate the numbers of deaths associated with HCV infection.
      Two sensitivity analyses were developed to test the robustness of the results.
      RESULTS: Our model shows total productivity losses attributable to HCV infection
      of 1054.7 million euros over the period analysed. The trend in productivity
      losses is decreasing over the period. This result is because of improvements in
      health outcomes, reflected in the reduction of the number of years of potential
      productive life lost. Of the total estimated losses, 18.6% were because of
      hepatitis C, 24.6% because of hepatocellular carcinoma, 30.1% because of
      cirrhosis, 15.9% because of other liver diseases and 10.7% because of HIV-HCV
      coinfection. CONCLUSION: The results show that premature mortality attributable
      to hepatitis C involves significant productivity losses. This highlights the need
      to extend the analysis to consider other social costs and obtain a more complete
      picture of the actual economic impact of hepatitis C infection.

PMID- 25853932
TI  - Manipulating Simple Reactive Chemical Units: Fishing for Alkaloids from Complex
      Mixtures.
AB  - This Concept article describes how key C10 molecular scaffolds, too reactive to
      be obtained through classical multistep synthesis, were targeted in the most
      simple reaction conditions, reproducing those that may be encountered in living
      cells. The rationale was that small amounts of these reactive intermediates might
      be formed in situ from cheap and abundant reactants (i.e., glutaraldehyde and
      tetrahydropyridine) resulting, upon further rearrangement in "complex mixtures"
      from which natural substances would arise. From five types of mixtures, at least
      six full carbon skeletons of known natural substances were formed spontaneously.
      This work also led to the discovery of new plausible biosynthetic achiral
      precursors in the Nitraria metabolism. 

PMID- 25853933
TI  - Motion-based threat detection using microrods: experiments and numerical
      simulations.
AB  - Motion-based chemical sensing using microscale particles has attracted
      considerable recent attention. In this paper, we report on new experiments and
      Brownian dynamics simulations that cast light on the dynamics of both passive and
      active microrods (gold wires and gold-platinum micromotors) in a silver ion
      gradient. We demonstrate that such microrods can be used for threat detection in
      the form of a silver ion source, allowing for the determination of both the
      location of the source and concentration of silver. This threat detection
      strategy relies on the diffusiophoretic motion of both passive and active
      microrods in the ionic gradient and on the speed acceleration of the Au-Pt
      micromotors in the presence of silver ions. A Langevin model describing the
      microrod dynamics and accounting for all of these effects is presented, and key
      model parameters are extracted from the experimental data, thereby providing a
      reliable estimate for the full spatiotemporal distribution of the silver ions in
      the vicinity of the source. 

PMID- 25853934
TI  - Average genome size estimation improves comparative metagenomics and sheds light
      on the functional ecology of the human microbiome.
AB  - Average genome size is an important, yet often overlooked, property of microbial
      communities. We developed MicrobeCensus to rapidly and accurately estimate
      average genome size from shotgun metagenomic data and applied our tool to 1,352
      human microbiome samples. We found that average genome size differs significantly
      within and between body sites and tracks with major functional and taxonomic
      differences. In the gut, average genome size is positively correlated with the
      abundance of Bacteroides and genes related to carbohydrate metabolism.
      Importantly, we found that average genome size variation can bias comparative
      analyses, and that normalization improves detection of differentially abundant
      genes. 

PMID- 25853935
TI  - Levosimendan and nesiritide as a combination therapy in patients with acute heart
      failure.
AB  - BACKGROUND: Individually, levosimendan and nesiritide have been associated with
      substantial clinical benefits for the treatment of acute decompensated heart
      failure (ADHF). The aim of this study was to evaluate the efficacy of the
      combination of levosimendan and nesiritide for the treatment of ADHF. METHODS:
      One hundred and twenty patients were randomly assigned to control, levosimendan,
      nesiritide or combination groups. The patients received 2 drugs: 1 was
      levosimendan or placebo A and the other was nesiritide or placebo B. The primary
      end points were rates of clinical effectiveness at 1, 3, 5 and 9 days after the
      start of therapy. RESULTS: Nine days after the initiation of drug infusion, the
      clinical effectiveness rate in the combination group was better than that in the
      control group (odds ratio: 1.43, 95% confidence interval: 0.46-2.41, P = 0.004).
      The combination treatment also resulted in higher rates of clinical effectiveness
      than individually provided levosimendan or nesiritide at 1 day (both P = 0.04) or
      placebo at 1, 3 or 5 days (P = 0.002, 0.006 and 0.009, respectively). The
      combination method was associated with fewer deaths and readmissions, as compared
      with the rate observed in the placebo group during the 3-month follow-up (hazard
      ratio: 0.43, 95% confidence interval: 0.19-0.96, P = 0.038). CONCLUSIONS: Among
      patients with ADHF, intravenous infusion of levosimendan and nesiritide was
      superior to placebo and single-drug therapies in terms of improvements in
      clinical conditions during the early stages of therapy.

PMID- 25853937
TI  - Current rectifying and resistive switching in high density BiFeO3 nanocapacitor
      arrays on Nb-SrTiO3 substrates.
AB  - Ultrahigh density well-registered oxide nanocapacitors are very essential for
      large scale integrated microelectronic devices. We report the fabrication of well
      ordered multiferroic BiFeO3 nanocapacitor arrays by a combination of pulsed laser
      deposition (PLD) method and anodic aluminum oxide (AAO) template method. The
      capacitor cells consist of BiFeO3/SrRuO3 (BFO/SRO) heterostructural nanodots on
      conductive Nb-doped SrTiO3 (Nb-STO) substrates with a lateral size of ~60 nm.
      These capacitors also show reversible polarization domain structures, and well
      established piezoresponse hysteresis loops. Moreover, apparent current
      rectification and resistive switching behaviors were identified in these
      nanocapacitor cells using conductive-AFM technique, which are attributed to the
      polarization modulated p-n junctions. These make it possible to utilize these
      nanocapacitors in high-density (>100 Gbit/inch(2)) nonvolatile memories and other
      oxide nanoelectronic devices. 

PMID- 25853938
TI  - PI3Kbeta inhibitor TGX221 selectively inhibits renal cell carcinoma cells with
      both VHL and SETD2 mutations and links multiple pathways.
AB  - We aimed to exploit novel compounds with high selectivity to clear cell renal
      cell carcinoma (ccRCC) with common mutations. Using the GDSC databases, we
      searched for compounds with high selectivity for ccRCC with VHL and/or SETD2
      mutations. Clinical impact and gene interactions were analysed using TCGA
      database. In vitro and in vivo studies were performed to validate the inhibitory
      effects of the compound. We identified the selective PI3Kbeta inhibitor TGX221 as
      a selective inhibitor for ccRCC with both VHL and SETD2 mutations. TGX221 also
      targeted cancer cells with CDKN2A and PTEN mutations. Changes in PTEN and CDKN2A
      gene sets were associated with worsened prognosis of ccRCC. TGX221 substantially
      and selectively inhibited the down stream products of VHL, SETD2, and PTEN in
      ccRCC cells with VHL and SETD2 mutations. TGX221 also exhibited significant
      selectivity in inhibiting cell motility and tumourigenesis of ccRCC cells with
      VHL and SETD2 mutations. TGX221 is a novel inhibitor with high selectivity for
      ccRCC with VHL and SETD2 mutations. It also targeted PTEN and CDKN2A mutations.
      How those genes were associated with PI3Kbeta warranted further investigations. 

PMID- 25853940
TI  - Comparison of Dermatology and Allergy Guidelines for Atopic Dermatitis
      Management.
AB  - IMPORTANCE: Atopic dermatitis (AD) is a common skin condition treated by
      dermatologists, allergists, pediatricians, and primary care physicians. Several
      treatment guidelines and therapeutic parameters exist for the management of this
      disease. Health care professionals may be unaware of guidelines created by
      specialty organizations other than their own. OBJECTIVE: To review, compare, and
      contrast the most recent AD management guidelines. EVIDENCE REVIEW: The
      guidelines for AD management published by the American Academy of Dermatology
      2014 work group were compared with those created by the 2012 Joint Task Force on
      Practice Parameters representing the American Academy of Allergy, Asthma &
      Immunology; the American College of Allergy, Asthma & Immunology; and the Joint
      Council of Allergy, Asthma & Immunology. International guidelines created by the
      2012 European Task Force on Atopic Dermatitis and the 2013 Asia-Pacific Consensus
      Group for Atopic Dermatitis were also considered. FINDINGS: Several differences
      among the guidelines suggest that there may be disparity in the perceptions of AD
      between US dermatologists and allergists and health care professionals in other
      areas of the world. There are notable differences among the guidelines regarding
      the recommendations for the use of diluted bleach baths, vitamin D, and
      environmental modifications. CONCLUSIONS AND RELEVANCE: Comparison of different
      guidelines may ultimately augment knowledge of treatment strategies and enhance
      realization of biases in the understanding and management of AD.

PMID- 25853941
TI  - [Unilateral Choroidal Folds due to Scleral Calcifications as a Result of
      Alimentary-induced Hypercalcaemia].

PMID- 25853939
TI  - Urban vs Rural Residence and the Prevalence of Depression and Mood Disorder Among
      African American Women and Non-Hispanic White Women.
AB  - IMPORTANCE: There is a paucity of research among African Americans and rural
      residents. Little is known about the association between urbanicity and
      depression or about the interaction of urbanicity, race/ethnicity, and sex on
      depression and mood disorder prevalence. OBJECTIVE: To examine the interaction of
      urbanicity and race/ethnicity on lifetime and 12-month major depressive disorder
      (MDD) and mood disorder prevalence for African American women and non-Hispanic
      white women. DESIGN, SETTING, AND PARTICIPANTS: The US National Survey of
      American Life data were used to examine the interaction of urbanicity and
      race/ethnicity on lifetime and 12-month diagnoses of DSM-IV MDD and mood disorder
      among female respondents, who included noninstitutionalized African American,
      Caribbean black, and non-Hispanic white women in the United States between
      February 2001 and June 2003. Participants included 1462 African American women
      and 341 non-Hispanic white women recruited from the South because all suburban
      and rural National Survey of American Life respondents resided in this region.
      Bivariate multiple logistic regression and adjusted prevalence analyses were
      performed. Urban, suburban, or rural location (assessed via Rural-Urban Continuum
      Codes), self-reported race/ethnicity, and sociodemographic factors (age,
      education, household income, and marital status) were included in the analysis.
      MAIN OUTCOMES AND MEASURES: Lifetime and 12-month MDD and mood disorder assessed
      via the World Mental Health Composite International Diagnostic Interview.
      RESULTS: Compared with urban African American women, rural African American women
      had a significantly lower odds of meeting criteria for lifetime (odds ratio [OR],
      0.39; 95% CI, 0.23-0.65) and 12-month (OR, 0.29; 95% CI, 0.18-0.46) MDD and for
      lifetime (F = 0.46; 95% CI, 0.29-0.73) and 12-month (F = 0.42; 95% CI, 0.26-0.66)
      mood disorder. However, the interaction of urbanicity and race/ethnicity
      suggested that rural non-Hispanic white women had a significantly higher odds of
      meeting criteria for lifetime (OR, 2.76; 95% CI, 1.22-6.24) and 12-month (OR,
      9.48; 95% CI, 4.65-19.34) MDD and for lifetime (OR, 2.27; 95% CI, 1.06-4.87) and
      12-month (OR, 5.99; 95% CI, 3.01-11.94) mood disorder than rural African American
      women. Adjusted prevalence analyses revealed significantly lower rates of
      lifetime (4.2%) and 12-month (1.5%) MDD among rural African American women than
      their urban counterparts (10.4% vs 5.3%; P <= .01). The same pattern was found
      for mood disorder, with rural African American women experiencing significantly
      lower rates of lifetime (6.7%) and 12-month (3.3%) mood disorder when compared to
      urban African American women (13.9% vs 7.6%; P <= .01) Conversely, rural non
      Hispanic white women had significantly higher rates of 12-month MDD (10.3%) and
      mood disorder (10.3%) than their urban counterparts (3.7% vs 3.8%; P <= .01).
      CONCLUSIONS AND RELEVANCE: Rural residence differentially influences MDD and mood
      disorder prevalence among African American women and non-Hispanic white women.
      These findings offer a first step toward understanding the cumulative effect of
      rural residence and race/ethnicity on women's depression prevalence, suggesting
      the need for further research in this area.

PMID- 25853942
TI  - [Binocular Fluocinolone Acetonide Intravitreal Implant for Therapy-Resistant
      Diabetic Maculopathy].

PMID- 25853943
TI  - [Central Scotoma and Testicular Pain].

PMID- 25853944
TI  - [Intraoperative Measurement of Refraction with a Hand-Held Autorefractometer].
AB  - PURPOSE: The aim of this study was to evaluate an intraoperative measurement of
      objective refraction with a hand-held retinomax instrument. METHODS: At the end
      of cataract surgery objective refraction in a lying position was measured with a
      retinomax instrument. On the first postoperative day the same measurement was
      performed with a retinomax and a standard autorefractometer. To evaluate the
      differences between measurements, the spherical equivalent (SE) and Jackson's
      cross cylinder at 0 degrees  (J0) and 45 degrees  (J45) was used. RESULTS: 103
      eyes were included. 95 of them had normal cataract surgery. Differences between
      retinomax at the operative day and the standard autorefractometer were 0.68 +/-
      2.58 D in SE, 0.05 +/- 1.4D in J0 and 0.05 +/- 1.4D in J45. There were no
      statistically significant differences between the groups. CONCLUSION:
      Intraoperative measurement of the refraction with a retinomax can predict the
      postoperative refraction. Nevertheless, in a few patients great differences may
      occur.

PMID- 25853945
TI  - [Postoperative Results after Implantation of a Toric, Aspheric Intraocular Lens].
AB  - PURPOSE: The purpose of this study was to evaluate the functional results and
      quality of vision after implantation of an aspheric, aberration-neutral,
      monofocal toric intraocular lens (IOL). PATIENTS AND METHODS: 18 eyes of 13
      patients were enrolled in this prospective clinical study. The T-flex aspheric,
      aberration-free toric IOL (Rayner Intraocular Lenses Limited, U. K.) was
      implanted after femtosecond or standard phacoemulsification. Follow-up
      examinations were performed two to four months after surgery; these included
      subjective refraction, ETDRS uncorrected (UDVA) and corrected distance visual
      acuity (CDVA), wavefront analysis, measurements of stray light (C-Quant), and a
      questionnaire. RESULTS: Median UDVA was 0.06 logMAR (range: 0.30 to - 0.18
      logMAR) postoperatively. Median CDVA increased from 0.20 logMAR (range: 0.64 to
      0.00 logMAR) preoperatively to - 0.07 logMAR (range: 0.16 to - 0.26 logMAR)
      postoperatively. The median difference between achieved versus intended spherical
      equivalent was - 0.08 D (range: - 1.25 to + 0.65 D). Median subjective cylinder
      improved from - 2.00 D (range: - 6.50 to - 0.25 D) preoperatively to - 0.50 D
      (range: - 1.25 to 0.00 D) postoperatively. The median spherical aberrations (6 mm
      pupil size) were - 0.38 um (range: - 0.69 to - 0.10 um) postoperatively.
      Measurements of stray light (C-Quant) revealed a median value of 1.28 log(s)
      (range: 0.92 to 1.61 log[s]). CONCLUSION: The T-flex aspheric toric IOL provided
      beneficial and predictable functional results after surgery. The implantation of
      the T-flex is an effective method to correct a large range of corneal
      astigmatism.

PMID- 25853946
TI  - [Diurnal Fluctuations of Intraocular Pressure, Blood Pressure, and Ocular
      Perfusion Pressure in Glaucoma Patients].
AB  - BACKGROUND: An elevated intraocular pressure remains the main risk factor for the
      development and progression of glaucoma but other factors such as fluctuations of
      the intraocular pressure, the blood pressure, and the ocular perfusion pressure
      are gaining in importance. The influence of the anti-glaucomatous therapies on
      these parameters is barely investigated. This study investigates 1) a correlation
      between the fluctuations of the intraocular pressure, the blood pressure and the
      ocular perfusion pressure with the severity of the glaucoma damage and 2) if
      these parameters can be influenced by different anti-glaucomatous therapies.
      MATERIAL AND METHODS: Data from 121 glaucoma patients who had been hospitalised
      for 24-hour measurements of the intraocular pressure and blood pressure between
      2003 and 2012 were analysed retrospectively. The patients were divided into
      groups by the severity of the glaucoma damage and by their anti-glaucomatous
      therapy. Mean values for the intraocular pressure, the blood pressure and the
      ocular perfusion pressure were calculated and correlated with the individual
      groups. The statistical analysis was performed with SPSS21.0 using Kruskal-Wallis
      and Mann-Whitney U tests for the comparison of the groups. RESULTS with p < 0.05
      were considered statistically significant. RESULTS: The severity of the glaucoma
      damage correlated significantly with higher mean values of the intraocular
      pressure and its fluctuations, as well as with a nocturnal decrease of the blood
      pressure and low mean values of the ocular perfusion pressure (p < 0.0001). The
      anti-glaucomatous therapy decreased the intraocular pressure to normal values. A
      monotherapy with carboanhydrase inhibitors correlated with the lowest
      fluctuations of the ocular perfusion pressure while a quadri-therapy was
      associated with higher values of the intraocular pressure and its fluctuations.
      The anti-glaucomatous therapy did not show an association with the blood pressure
      or the ocular perfusion pressure. CONCLUSION: Glaucoma is negatively influenced
      by high intraocular pressure, nocturnal blood pressure decreases and ocular
      perfusion pressure fluctuations. A monotherapy with carboanhydrase inhibitors
      seems to be sufficient to decrease fluctuations of the intraocular pressure.
      Patients with a quadri-therapy should be monitored regularly as they present high
      values of intraocular pressure and its fluctuations. A hospitalisation of the
      patients with 24-hour measurements of the intraocular pressure and blood pressure
      provides information needed to improve the therapy or decide about surgical
      interventions.

PMID- 25853947
TI  - [Albrecht von Graefe (1828-1870) and Ophthalmic Pathology].

PMID- 25853948
TI  - [Iatrogenic Keratectasia: A Review].
AB  - Iatrogenic corneal ectasia is a rare complication but also one of the most feared
      situations that can occur after uneventful corneal laser surgery. Ectatic changes
      can occur as early as 1 week or can be delayed up to several years after LASIK.
      The actual incidence of ectasia is undetermined, an incidence rate of 0.04 to
      almost 2.8 % has been reported. Ectasia is most common following LASIK; however,
      cases have been reported following PRK and other corneal refractive procedures.
      Keratectasia shows progressive myopia, irregular astigmatism, ghosting,
      fluctuating vision and problems with scotopic vision. The progression leads to
      severe loss of corrected visual acuity. Risk factors are thin corneas < 500 um, a
      pathological corneal topography, a residual stromal bed < 300 um, high myopia > 8
      D, young (female) age < 25 years, atopic dermatitis, allergies, family history
      for keratokonus and collagen diseases and retreatments. Treatment of choice is a
      cross-linking with riboflavin/UVA light with contact lenses. In severe cases a
      penetrating or a deep anterior lamellar graft is necessary. 

PMID- 25853950
TI  - Pulmonary vascular and airway responses to systemic vasoconstrictors in
      anesthetized BALB/c mice.
AB  - There is no systematic study in which the effects of vasoactive substances were
      investigated on pulmonary vascular resistance (PVR) in in vivo mouse by directly
      measuring cardiac output and the inflow and outflow pressures in the pulmonary
      circulation. We determined the responses of PVR, total peripheral resistance
      (TPR), and airway pressure (AWP) to angiotensin II, endothelin-1, vasopressin,
      phenylephrine, and thromboxane A2 analog U46619 in anesthetized BALB/c mice.
      Pulmonary arterial pressure, left atrial pressure (LAP), and aortic blood flow
      were measured. TPR increased dose-dependently in response to consecutive
      administration of all vasoconstrictors except vasopressin which reduced TPR at
      the highest dose of 100 nmol/kg. At high doses of vasoconstrictors, pulmonary
      arterial pressure and AWP increased due to increased LAP, as demonstrated by the
      separate LAP elevation experiments. When LAP transiently increased at high doses,
      PVR did not increase but decreased. Nonetheless, enodothelin-1, angiotensin II,
      and U46619 increased PVR. Vasopressin at 100 nmol/kg increased AWP without LAP
      elevation. In conclusion, the high doses of the vasoconstrictors studied here
      exert indirectly a transient pulmonary vasodilatory and AWP increasing actions
      due to pulmonary congestion evoked by strong systemic vasoconstriction.
      Nevertheless, enodothelin-1, angiotensin II, and U46619 cause pulmonary
      vasoconstriction, and vasopressin constricts airway in anesthetized BALB/c mice. 

PMID- 25853951
TI  - Adipose-Derived Stem Cells Accelerate Diabetic Wound Healing Through the
      Induction of Autocrine and Paracrine Effects.
AB  - Cell-based therapy is an attractive approach for the treatment of chronic
      nonhealing wounds. This study investigated whether adipose-derived stem cells
      (ASCs) can accelerate diabetic wound healing and traffic in the engraftment of
      ASCs. Dorsal full-thickness skin wound defects (6 * 5 cm) were created in a
      streptozotocin (STZ)-induced diabetes rodent model. Group I served as a
      nondiabetic normal control, group II served as a diabetic control without ASCs,
      and group III included rats that were injected subcutaneously in the wound margin
      twice with nondiabetic ASCs (1 * 10(7) ASCs/dose). The wound healing was assessed
      clinically. Histological examination and immunohistochemical analyses of
      periwound tissue were performed. Green fluorescence protein (GFP)(+)-ASCs were
      used to examine the engraftment of these cells after injection. XenoLight DiR
      labeled ASCs were implanted to detect migration ability using an IVIS imaging
      system. Results revealed that complete wound healing time statistically decreased
      in the ASC-treated group compared to the controls (p < 0.001). Histological
      examination revealed the ASC-treated group showed a significant reduction in the
      proinflammatory reaction, with significantly increased levels of EGF, VEGF, rPH,
      and Ki-67 expression compared to the controls. The populations of GFP(+)-ASCs in
      circulating blood significantly increased after ASC injection compared to those
      of controls. Immunofluorescence staining showed GFP(+)-ASCs significantly
      accumulated in the subdermal layer of the wound margin and increased angiogenesis
      via vWF and VEGF expression after injection. IVIS analysis revealed ASCs could
      exist and home into the periwound area up to 8 weeks postimplantation. In
      conclusion, ASCs significantly enhanced diabetic wound healing, engrafted into
      the local wound tissue, and implanted into circulating blood. ASC treatment
      stimulated neoangiogenesis and increased tissue regeneration through paracrine
      and autocrine mechanisms.

PMID- 25853949
TI  - Role of the sympathetic autonomic nervous system in hypoxic remodeling of the
      fetal cerebral vasculature.
AB  - Fetal hypoxia triggers compensatory angiogenesis and remodeling through
      mechanisms not fully elucidated. In response to hypoxia, hypoxia-inducible factor
      drives expression of cytokines that exert multiple effects on cerebral
      structures. Among these, the artery wall is composed of a heterogeneous cell mix
      and exhibits distinct patterns of cellular differentiation and reactivity.
      Governing these patterns are the vascular endothelium, smooth muscle (SM),
      adventitia, sympathetic perivascular nerves (SPN), and the parenchyma. Although
      an extensive literature details effects of nonneuronal factors on cerebral
      arteries, the trophic role of perivascular nerves remains unclear. Hypoxia
      increases sympathetic innervation with subsequent release of norepinephrine (NE),
      neuropeptide-Y (NPY), and adenosine triphosphate, which exert motor and trophic
      effects on cerebral arteries and influence dynamic transitions among SM
      phenotypes. Our data also suggest that the cerebrovasculature reacts very
      differently to hypoxia in fetuses and adults, and we hypothesize that these
      differences arise from age-related differences in arterial SM phenotype
      reactivity and proximity to trophic factors, particularly of neural origin. We
      provide an integration of recent literature focused on mechanisms by which SPN
      mediate hypoxic remodeling. Our recent findings suggest that trophic effects of
      SPN on cerebral arteries accelerate functional maturation through shifts in SM
      phenotype in an age-dependent manner. 

PMID- 25853952
TI  - Effect of fruit vinegars on liver damage and oxidative stress in high-fat-fed
      rats.
AB  - CONTEXT: Vinegar has long been used as a condiment and a traditional medicine
      worldwide. OBJECTIVE: The current study investigates the antioxidant effect of
      three types of fruit vinegars (FV) namely pomegranate [Punica granatum L.
      (Punicaceae)], prickly pear [Opuntia ficus-indica (L.) Mill. (Cactaceae)], and
      apple [Malus domestica Borkh. (Rosaceae)] vinegars in high-fat diet (HFD)-induced
      hyperlipidemic Wistar rats. MATERIALS AND METHODS: Fifty male Wistar rats were
      divided into five groups; HFD (80 cal/d) fed rats were orally dosed with fruit
      vinegars (7 ml/kg) once daily for 28 weeks. At the end of the experiment, lipid
      profile, lipid peroxidation products, antioxidant enzymes, and trace elements
      were assessed in serum. In addition, a liver histopathological study was
      performed. RESULTS: HFD showed a significant increase (p <= 0.05) in lipid
      profile and TBARS levels when compared with normal control. Daily oral
      administration of FV normalized various biochemical, metabolic, and
      histopathological changes. However, pomegranate vinegar exhibited a very
      significant (p <= 0.001) reduction in lipid profile levels (total cholesterol:
      165%, triglycerides: 68%, LDL-c: 76%, and atherogenic index: 80%), whereas an
      increase in antioxidant status (SOD: 7-fold, GPx: 4.81-fold, GRx: 1.66-fold, and
      TAS: 3.45-fold) when compared with hyperlipidemic control. Histopathological
      examinations also confirmed the protective effects of pomegranate vinegar against
      lipid accumulation and the improvement of hepatic lesions. DISCUSSION AND
      CONCLUSION: The fruit vinegars regulate lipid metabolism and decrease liver
      damage in high-fat fed rats as shown in this study.

PMID- 25853953
TI  - Formulation, characterization, and geno/cytotoxicity studies of galbanic acid
      loaded solid lipid nanoparticles.
AB  - CONTEXT: Galbanic acid (GBA) is a sesquiterpene coumarin with different medicinal
      properties and anticancer effects. OBJECTIVE: To improve the anticancer
      activities of GBA, in the current study, we aimed to fabricate GBA-loaded solid
      lipid nanoparticles (GBA-SLNs) and study their biological activities in vitro.
      MATERIALS AND METHODS: Hot homogenization was used for preparation of GBA-SLNs.
      The encapsulation efficiency (EE) and drug loading (DL) and in vitro release were
      determined. MTT, DAPI, DNA fragmentation, comet, and Anexin V apoptosis assays
      were used to compare the anti-cell proliferation and genotoxicity properties of
      GBA and GBA-SLNs against A549 cells and HUVEC to detect apoptosis and DNA damage
      in the final concentration of 100 uM after 48 h treatment. RESULTS: Scanning
      electron microscopy (SEM) and particle size analysis showed spherical SLNs (92
      nm), monodispersed distribution, and zeta potential of -23.39 mV. High EE (>98%)
      and long-term in vitro release were achieved. The stability of GBA-SLNs in
      aqueous medium was approved after 3 months in terms of size and polydispersity
      index. GBA was able to inhibit A549 growth with an IC50 value of 62 uM at 48 h.
      Although GBA-SLNs could also inhibit the growth rate of A549 cells, the effect is
      perceived after 48 h, as approved by the quantitative expression of Bcl-xL and
      Casp 9 genes, and also genotoxicity assays. CONCLUSION: Long-term apoptotic
      effect of GBA-SLNs compared with GBA may be due to the accumulation of GBA-SLNs
      in the tumor site because of deviant tumor pathology. Our data confirmed that
      SLNs could be exploited for sustained lipophilic GBA delivery.

PMID- 25853955
TI  - Antiglycation therapy: Discovery of promising antiglycation agents for the
      management of diabetic complications.
AB  - CONTEXT: During diabetes mellitus, non-enzymatic reaction between amino groups of
      protein and carbonyl of reducing sugars (Millard reaction) is responsible for the
      major diabetic complications. Various efforts have been made to influence the
      process of protein glycation. OBJECTIVES: This review article provides an
      extensive survey of various studies published in scientific literature to
      understand the process of protein glycation and its measurement. Moreover,
      evaluation and identification of potential inhibitors (antiglycation agents) of
      protein glycation from natural and synthetic sources and their mechanism of
      action in vitro and in vivo are also addressed. METHOD: In this review article,
      the mechanism involved in the formation of advanced glycation end products (AGEs)
      is discussed, while in second and third parts, promising antiglycation agents of
      natural and synthetic sources have been reviewed, respectively. Finally, in vivo
      studies have been addressed. This review is mainly compiled from important
      databases such as Science, Direct, Chemical Abstracts, SciFinder, and PubMed.
      RESULTS: During the last two decades, various attempts have been made to inhibit
      the process of protein glycation. New potent inhibitors of protein glycation
      belonging to different classes such as flavonoids, alkaloids, terpenes,
      benzenediol Schiff bases, substituted indol, and thio compounds have been
      identified. CONCLUSION: Antiglycation therapy will be an effective strategy in
      future to prevent the formation of AGEs for the management of late diabetic
      complications Current review article highlighted various compounds of natural and
      synthetic origins identified previously to inhibit the protein glycation and
      formation of AGEs in vitro and in vivo.

PMID- 25853954
TI  - Preparation, characterization, and pharmacokinetics study of capsaicin via
      hydroxypropyl-beta-cyclodextrin encapsulation.
AB  - CONTEXT: Capsaicin (CAP) is an effective drug in the treatment of pain and
      cancer. However, its practical administration has been limited due to poor
      aqueous solubility and bioavailability, as well as strong gastrointestinal
      irritation. OBJECTIVE: The objective of this study is to improve the solubility
      and oral bioavailability of CAP by reducing irritation via hydroxypropyl-beta
      cyclodextrin (HP-beta-CD) inclusion complex formulation, in vitro and in vivo
      analysis. MATERIALS AND METHODS: The complex (CAP-HP-beta-CD) was developed via
      the magnetic stirring method and characterized using ultraviolet (UV) absorption
      spectrometry, infrared radiation (IR) spectroscopy, and differential scanning
      calorimetry (DSC). Rats were treated with CAP (90 mg * kg(-1)) or CAP-HP-beta-CD
      (corresponding to 90 mg * kg(-1) CAP) by gavage, and all the plasma samples were
      analyzed with high performance liquid chromatography (HPLC). RESULTS: The results
      of UV, IR, and DSC showed that an acceptable CAP-HP-beta-CD (encapsulation
      efficiency, 75.83%; drug loading, 7.44%) was formulated. In vitro release study
      of CAP-HP-beta-CD revealed that the cumulative release of CAP from HP-beta-CD
      encapsulation was obviously enhanced (above 80% increases). Similarly, the in
      vivo pharmacokinetics parameters also increased, Cmax (from 737.94 to 1117.57 ng
      * mL(-1)), AUC0- (from 5285.9 to 7409.8 ng * h * mL(-1)) or relative
      bioavailability (139.38%). The gastric irritation bioassay further showed that
      the CAP-HP-beta-CD was far better than free CAP. DISCUSSION AND CONCLUSION: CAP
      exhibited significant aqueous solubility and oral bioavailability, as well as
      minimal irritation effect after forming inclusion complex with HP-beta-CD.
      Therefore, these findings could provide an equally important alternative option
      for the clinical use of CAP.

PMID- 25853956
TI  - Antioxidant and alpha-glucosidase inhibitory activities of Achillea tenorii.
AB  - CONTEXT: There is a need for the discovery of novel natural remedies to prevent
      and treat metabolic disorders such as hyperglycemia, type II non-insulin
      dependent diabetes mellitus, and obesity. Several Achillea species have been
      utilized for centuries all around the world and are generally considered
      effective as hypoglycemic. OBJECTIVE: Considering the ethnobotanical uses of
      Achillea genus, we evaluated the in vitro inhibitory activity of Achillea tenorii
      Grande (Asteraceae) extract on alpha-glucosidase, which is a valuable target to
      prevent and treat metabolic disorders. We also tested its antioxidant activity.
      Moreover, the phytochemical profile was discussed from a chemotaxonomic point of
      view. MATERIALS AND METHODS: In vitro alpha-glucosidase inhibition of crude
      ethanolic extract obtained from the aerial parts was assayed as well as the in
      vitro antioxidant activity (ABTS, DPPH, and FRAP-FZ tests) was measured. The
      extract was characterized from a phytochemical point of view by means of
      spectroscopic analysis. RESULTS: The extract results endowed with alpha
      glucosidase inhibitory activity (IC50 32 ug/mL) with a particular mechanism of
      action definable as un-competitive, which differed from the mechanism observed
      for the best-known alpha-glucosidase inhibitor (acarbose and miglitol). In
      addition, a considerable antioxidant potential has been found for A. tenorii
      extract, which resulted mainly constituted by phenolic compounds such as
      caffeoylquinic acids and flavonoids. DISCUSSION AND CONCLUSIONS: These results
      suggest the potential of A. tenorii as a possible natural remedy to prevent and
      treat metabolic disorders of carbohydrates.

PMID- 25853957
TI  - Influence of kaempferol, a flavonoid compound, on membrane-bound ATPases in
      streptozotocin-induced diabetic rats.
AB  - CONTEXT: Kaempferol is a flavonoid found in many edible plants (e.g. tea,
      cabbage, beans, tomato, strawberries, and grapes) and in plants or botanical
      products commonly used in traditional medicine. Numerous preclinical studies have
      shown that kaempferol have a wide range of pharmacological activities, including
      antioxidant, anti-inflammatory, anticancer, cardioprotective, neuroprotective,
      and antidiabetic activities. OBJECTIVE: The present study investigates the effect
      of kaempferol on membrane-bound ATPases in erythrocytes and in liver, kidney, and
      heart of streptozotocin (STZ)-induced diabetic rats. MATERIALS AND METHODS:
      Diabetes was induced into adult male albino rats of the Wistar strain, by
      intraperitoneal administration of STZ (40 mg/kg body weight (BW)). Kaempferol
      (100 mg/kg BW) or glibenclamide (600 ug/kg BW) was administered orally once daily
      for 45 d to normal and STZ-induced diabetic rats. The effects of kaempferol on
      membrane-bound ATPases (total ATPase, Na(+)/K(+)-ATPase, Ca(2+)-ATPase, and
      Mg(2+)-ATPase) activity in erythrocytes and in liver, kidney, and heart were
      determined. RESULTS: In our study, diabetic rats had significantly (p < 0.05)
      decreased activities of total ATPases, Na(+)/K(+)-ATPase, Ca(2+)-ATPase, and
      Mg(2+)-ATPase in erythrocytes and tissues. Oral administration of kaempferol (100
      mg/kg BW) or glibenclamide (600 ug/kg BW) for a period of 45 d resulted in
      significant (p < 0.05) reversal of these enzymes' activities to near normal in
      erythrocytes and tissues when compared with diabetic control rats. DISCUSSION AND
      CONCLUSION: Thus, obtained results indicate that administration of kaempferol has
      the potential to restore deranged activity of membrane-bound ATPases in STZ
      induced diabetic rats. Further detailed investigation is necessary to discover
      kaempferol's action mechanism.

PMID- 25853958
TI  - Macrophage activation induced by the polysaccharides isolated from the roots of
      Sanguisorba officinalis.
AB  - CONTEXT: Macrophage, involved at all stages of immune response, is an important
      component of the host defense system. Polysaccharides exist almost ubiquitously
      in medical plants and most of them possess immunomodulation and macrophage
      activation properties. OBJECTIVE: This study elucidates the effects on macrophage
      activation and molecular mechanism induced by the polysaccharides (SOPs) from the
      roots of Sanguisorba officinalis Linne (Rosaceae). MATERIALS AND METHODS:
      Polysaccharides (SOPs) from the roots of S. officinalis were obtained by water
      extraction and ethanol precipitation. Physicochemical characterization of SOPs
      was analyzed by phenol-sulfuric acid, m-hydroxydiphenyl, Bradford method, and gas
      chromatography. Phagocytic capacity of RAW 264.7 macrophages incubated with SOPs
      (25 and 100 MUg/ml) was determined by the aseptic neutral red method. Macrophages
      were incubated with SOPs (25 and 100 MUg/ml), and the TNF-alpha and NO the
      secretion were measured using ELISA kit and Griess reagent, respectively. In
      addition, TNF-alpha and iNOS transcripts were evaluated by semi-quantitative RT
      PCR, and NF-kappaB signaling activation was detected by Western blot assay.
      RESULTS: SOPs enhanced the phagocytosis capacity of macrophages to aseptic
      neutral red solution and increased TNF-alpha and NO secretion. The amounts of TNF
      alpha and iNOS transcript were increased significantly at the mRNA level when
      macrophages were exposed to SOPs. Meanwhile, the stimulation of macrophages by
      SOPs induced phosphorylation of p65 at serine 536 and a marked decrease of
      IkappaB expression. DISCUSSION AND CONCLUSION: These results suggested that SOPs
      exhibited significant macrophage activation properties through NF-kappaB
      signaling pathway and could be considered as a new immunopotentiator.

PMID- 25853959
TI  - Proulcerogenic effect of water extract of Boswellia sacra oleo gum resin in rats.
AB  - CONTEXT: The water extract of Boswellia sacra Flueck. (Burseraceae) is used in
      the treatment of gastric and hepatic disorders in the Arab countries. OBJECTIVE:
      The effect of Boswellia sacra water extract on gastric secretion and
      experimentally induced gastric ulcers in rats was studied. MATERIALS AND METHODS:
      Acetic acid-induced chronic gastric ulcers, pylorus ligation, aspirin-induced,
      ethanol-induced, and restraint plus cold stress-induced gastric ulcer models were
      employed. The effect on normal rats was also studied. The water extract of B.
      sacra was administered orally at doses of 2 and 5 ml/kg once daily ranging from
      single dose to 30 d treatment depending on the model. The extract was subjected
      to GC-MS analysis to determine the presence of various phytoconstituents.
      RESULTS: Boswellia sacra water extract (5 ml/kg, p.o (per os)) aggravated acetic
      acid-induced chronic ulcers, wherein an increase in ulcer index (p < 0.01) and
      ulcer score (p < 0.05) was observed. In pylorus-ligated rats, the extract
      increased gastric content volume (p < 0.01), free acidity (p < 0.01), total
      acidity (p < 0.01), ulcer index (p < 0.01), and pepsin activity (p < 0.05). There
      was no significant effect on the development of ethanol-induced and aspirin
      induced ulcers while an increase in the development of stress-induced ulcers was
      observed (p < 0.01). The extract did not produce any ulcers when administered to
      normal rats. The dose of 2 ml/kg was less proulcerogenic compared with 5 ml/kg.
      The GC-MS analysis revealed the presence of several phytoconstituents that
      included menthol, 3-cyclohexen-1-ol, and octanoic acid. CONCLUSION: Boswellia
      sacra water extract has proulcerogenic activity due to its gastric hypersecretory
      effect.

PMID- 25853960
TI  - Protective effect of centipedegrass against Abeta oligomerization and Abeta
      mediated cell death in PC12 cells.
AB  - CONTEXT: Alzheimer's disease (AD) is a neurodegenerative disorder characterized
      by the abnormal accumulation of beta-amyloid (Abeta). Multiple Abeta-aggregated
      species have been identified, and neurotoxicity appears to be correlated with the
      amount of non-fibrillar oligomers. Potent inhibitors of Abeta oligomer formation
      or Abeta-induced cell toxicity have emerged as attractive means of therapeutic
      intervention. Eremochloa ophiuroide Hack. (Poaceae), also known as centipedegrass
      (CG), originates from China and South America and is reported to contain several
      C-glycosyl flavones and phenolic constituents. OBJECTIVE: We investigated whether
      CG could suppress Abeta aggregation, BACE1 activity, and toxicity at neuronal
      cell. MATERIALS AND METHODS: The inhibitory effect of CG extracts toward
      aggregation of Abeta42 was investigated in the absence and presence of 50 ug/mL
      CG. We investigated the inhibitory effects of CG (0-5 ug/mL) on BACE1 using
      fluorescence resonance energy transfer (FRET)-based assay. The effects of CG (0
      75 ug/mL) on Abeta42-induced neurotoxicity were examined in PC12 cells in the
      presence or absence of maysin and its derivatives of CG. RESULTS: We isolated EA
      CG fraction (70% MeOH fraction from EtOAc extracts) from methanol extracts of CG,
      which contained approximately 60% maysin and its derivatives. In the present
      studies, we found that several Abeta oligomeric forms such as the monomer, dimer,
      trimer, and highly aggregated oligomeric forms were remarkably inhibited in the
      presence of 50 ug/mL of EA-CG. EA-CG also inhibited BACE1 enzyme activity in a
      dose-dependent manner. EA-CG treatment generated approximately 50% or 85%
      inhibition to the control at the tested concentrations of 1 or 5 ug/mL,
      respectively. Moreover, the neurotoxicity induced by Abeta42 was significantly
      reduced by treatment of EA-CG, and the 75 ug/mL EA-CG treatment significantly
      increased cell viability up to 82.5%. DISCUSSION AND CONCLUSION: These results
      suggested that the anti-Alzheimer's effects of CG occurred through inhibition of
      neuronal cell death by intervening with oligomeric Abeta formation and reducing
      BACE1 activity. Maysin in CG could be an excellent therapeutic candidate for the
      prevention of AD.

PMID- 25853961
TI  - Antiproliferative and apoptotic activities of extracts of Asclepias subulata.
AB  - CONTEXT: Asclepias subulata Decne. (Apocynaceae) is a shrub used in the Mexican
      traditional medicine for the treatment of cancer. OBJECTIVE: The objective of
      this study was to evaluate the antiproliferative activity of methanol extract of
      aerial parts of A. subulata and its fractions against different cancer cell
      lines. Additionally, we analyzed the mechanism of action of the active fractions.
      MATERIALS AND METHODS: Methanol extract fractions were prepared by serial
      extraction with n-hexane, ethyl acetate, and ethanol. The antiproliferative
      activity of methanol extract and its fractions was evaluated, against several
      murine (M12.C3.F6, RAW 264.7, and L929) and human (HeLa, A549, PC-3, LS 180, and
      ARPE-19) cell lines by the MTT assay, using concentrations of 0.4-400 ug/mL for
      48 h. Ethanol and residual fractions were separated using silica gel column.
      Apoptosis induction of cancer cells was evaluated by Annexin and JC-1 staining
      using flow cytometry. RESULTS: Methanol extract and its fractions showed
      antiproliferative activity against all human cancer cell lines tested. Methanol
      extract had the highest antiproliferative activity on A549 and HeLa cells (IC50
      values < 0.4 and 8.7 ug/mL, respectively). Ethanol and residual fractions exerted
      significant antiproliferative effect on A549 (IC50 < 0.4 ug/mL) and PC3 cells
      (IC50 1.4 and 5.1 ug/mL). Apoptotic assays showed that CEF7, CEF9, CRF6, and CRF5
      fractions induced mitochondrial depolarization in A549 cells, 70, 73, 77, and
      80%, respectively. Those fractions triggered the apoptosis mitochondrial pathway.
      CONCLUSION: Our data show that A. subulata extracts have potent antiproliferative
      properties on human cancer cell lines. This plant should be considered an
      important source of potent anticancer compounds.

PMID- 25853962
TI  - Artemisia arborescens "Powis Castle" extracts and alpha-thujone prevent fruit
      infestation by codling moth neonates.
AB  - CONTEXT: The codling moth, Cydia pomonella L. (Tortricidae), is a major
      cosmopolitan pest of the apple. The potential of plant-derived semiochemicals for
      codling moth control is poorly studied. OBJECTIVE: To evaluate the potential of
      crude extracts of five plants from the Asteraceae family: Artemisia absinthium
      L., Artemisia arborescens L. "Powis Castle", Artemisia annua L., and Artemisia
      ludoviciana Nutt. to prevent apple infestation by C. pomonella larvae and to
      identify the deterrent(s) in these plants. MATERIALS AND METHODS: Artemisia dried
      leaves were extracted in v/v mixture of 80% ethanol, 10% isopropanol, and 10% of
      methanol, and the extracts were analyzed using high-performance thin layer
      chromatography. Preference of fruit treated with test solutions (Artemisia
      extracts or alpha-thujone) versus fruit treated with solvent was studied using
      choice assays. RESULTS: alpha-Thujone was detected in A. arborescens extract at a
      concentration of 77.4 +/- 2.4 mg/g of dry tissue, localized between Rf 0.75 and
      0.79 and was absent from crude extracts of remaining Artemisia species. Material
      from each extract in the zone between Rf 0.75 and 0.79 was removed from
      chromatographic plates and tested for feeding deterrence. Only the material from
      A. arborescens showed feeding deterrent properties. Minimum concentrations that
      prevented fruit infestation were 10 mg/ml for alpha-thujone and 1 mg/ml for A.
      arborescens crude extract. DISCUSSION AND CONCLUSIONS: Artemisia arborescens
      contains chemicals that prevent apple infestation by codling moth neonates.
      Thujone is one of these chemicals, but it is not the only constituent of A.
      arborescens crude extract that prevents fruit infestation by codling moth
      neonates.

PMID- 25853963
TI  - Physicochemical properties and biological activities of Thai plant mucilages for
      artificial saliva preparation.
AB  - CONTEXT: Plant mucilages can be found in various parts of several Thai plants,
      which can be used as thickening, moisturizing, and lubricating agents in
      artificial saliva formulations. OBJECTIVE: The objective of this study was to
      evaluate the physicochemical properties, biological activity, and cytotoxicity of
      Thai plant mucilages. MATERIALS AND METHODS: The mucilages from Thai plants were
      extracted by various processes (temperature and pH variation, microwave oven,
      steam, and Tris-HCl buffer extraction). The viscosity and the rheology were
      evaluated using viscometer. Antioxidative activities including DPPH radical
      scavenging and metal chelating activities were investigated. The mucilages were
      determined for cytotoxicity on normal human gingival fibroblasts and anti
      adherent activity of Streptococcus mutans. RESULTS: Mucilages from Ocimum
      citriodorum Vis. (Lamiaceae), Artocarpus heterophyllus Lam. (Moraceae),
      Abelmoschus esculentus (Linn.) Moench. (Malvaceae), and Basella alba Linn.
      (Basellaceae) exhibited pseudoplastic non-Newtonian rheology. The highest DPPH
      radical-scavenging and metal-chelating activities were observed in the mucilages
      from B. alba (microwave, 3 min) and A. esculentus (microwave, 1 min) with the
      SC50 and MC50 values (50% of scavenging activity and 50% of metal chelating
      activity, respectively) of 0.71 +/- 0.32 and 1.11 +/- 0.52 mg/ml, respectively.
      Most mucilages exhibited no cytotoxicity to normal human gingival fibroblasts.
      The mucilage from A. esculentus (microwave, 5 min) gave the shortest wetting time
      of 2.75 +/- 0.51 min. The highest S. mutans adhesion inhibition was observed in
      A. esculentus (pH 11) of 5.39 +/- 9.70%. DISCUSSION AND CONCLUSION: This study
      has indicated the suitable physicochemical and biological properties and the
      potential application of mucilages from Thai plants for artificial saliva
      preparation.

PMID- 25853964
TI  - Synergistic anti-candidal activity and mode of action of Mentha piperita
      essential oil and its major components.
AB  - CONTEXT: Mentha piperita L. (Lamiaceae) has been used in folk medicine since
      antiquity. Its essential oil (mint EO) and major bioactive components have
      antimicrobial properties but their mechanism of action is still not clear.
      OBJECTIVE: The present work aims to elucidate M. piperita's anti-Candida activity
      and mode of action. MATERIALS AND METHODS: Chemical constituents of mint EO were
      identified by GC-MS by injecting 0.1 ml sample in a splitless mode. MIC was
      determined by the broth dilution method. Synergy with fluconazole (FLC) was
      evaluated by checkerboard assay and FICI. Mid log phase cells harvested from YPD
      media were used for proton extrusion measurement and the rate of glucose-induced
      H(+) efflux gives PM-ATPase activity. Cell membrane integrity was estimated by
      total ergosterol content and scanning microscopy at respective MIC and sub-MIC
      values. In vitro hemolytic activity was performed to rule out possible
      cytotoxicity of the test compounds. RESULTS: The MIC value of mint EO, carvone,
      menthol, and menthone was 225, 248, 500, and 4200 ug/ml, respectively. At their
      respective MICs, these compounds showed 47, 42, 35, and 29% decrease in PM-ATPase
      activity besides showing synergy with FLC. In case of FLC-resistant strains, the
      decrease in H(+) efflux was by 52, 48, 32, and 30%, a trend similar to the
      susceptible cases. Exposed Candida cells showed a 100% decrease in the ergosterol
      content, cell membrane breakage, and alterations in morphology. DISCUSSION AND
      CONCLUSION: Our studies suggest that mint EO and its lead compounds exert
      antifungal activity by reducing ergosterol levels, inhibiting PM-ATPase leading
      to intracellular acidification, and ultimately cell death. Our results suggest
      that mint EO and its constituents are potential antifungal agents and need to be
      further investigated.

PMID- 25853965
TI  - Cardioprotective effect of virgin coconut oil in heated palm oil diet-induced
      hypertensive rats.
AB  - CONTEXT: Virgin coconut oil (VCO) contains high antioxidant activity which may
      have protective effects on the heart in hypertensive rats. OBJECTIVES: The study
      investigated the effects of VCO on blood pressure and cardiac tissue by measuring
      angiotensin-converting enzyme (ACE) activity and its histomorphometry in rats fed
      with a heated palm oil (HPO) diet. MATERIALS AND METHODS: Thirty-two male Sprague
      Dawley rats were randomly divided into four groups: (i) control, (ii) orally
      given VCO (1.42 ml/kg), (iii) fed with a HPO (15%) diet, and (iv) fed with a HPO
      diet and supplemented with VCO (1.42 ml/kg, po) (HPO+VCO) for 16 weeks. Blood
      pressure was measured monthly. After 16 weeks, rat hearts were dissected for
      lipid peroxidation (TBARS) and ACE activity measurement and histomorphometric
      study. RESULTS: Systolic blood pressure was significantly increased in the HPO
      group compared with the control starting at week eight (112.91 +/- 1.32 versus
      98.08 +/- 3.61 mmHg, p < 0.05) which was prevented by VCO supplementation (91.73
      +/- 3.42 mmHg). The consumption of HPO increased TBARS and ACE activity in heart,
      which were inhibited by VCO supplementation. The increases in the myofiber width
      and area as well as nuclear size reduction in the HPO group were significantly
      prevented by VCO supplementation. CONCLUSION: These results suggested that VCO
      supplementation possesses a cardioprotective effect by preventing the increase in
      blood pressure via an antioxidant mechanism and remodeling in rats fed repeatedly
      with a HPO diet.

PMID- 25853966
TI  - Yacon roots (Smallanthus sonchifolius) improve oxidative stress in diabetic rats.
AB  - CONTEXT: Smallanthus sonchifolius (Poepp. and Endl.) H. Robinson, Asteraceae
      (yacon) roots are a natural product recognized by the traditional medicine to
      treat diabetes-related problems. There are no reports concerning the potential of
      yacon roots to reduce oxidative stress and ameliorate diabetes complications in
      diabetic animals. OBJECTIVE: This work analyzes the in vivo antioxidant activity
      and beneficial effects of yacon roots, using a model of streptozotocin-induced
      diabetes in rats. MATERIALS AND METHODS: Lipid peroxidation and other indicators
      of oxidative stress were determined in liver and kidney homogenates from non
      diabetic rats, untreated diabetic rats, and diabetic rats treated orally with
      yacon flour (340 mg fructooligosaccharide/kg/d) as a diet supplement for 90 d.
      Biochemical parameters were determined in liver, kidney, and blood at the end of
      the experimental period. RESULTS: Yacon supplementation to diabetic rats produced
      a significant decrease in malondialdehyde levels in both liver (-30.97%) and
      kidney (-19.15%). Hepatic superoxide dismutase and catalase activities were
      significantly lower in diabetic-treated rats (-13.46 and -64.33%, respectively)
      compared with diabetic controls. Similar results were observed in kidney. The
      treatment of diabetic rats produced an increase of glutathione peroxidase and
      glutathione levels in liver (172.50 and 35.91%, respectively) and kidney (177.78
      and 57.76%, respectively). Plasma cholesterol and triacylglycerol levels and
      liver fatty acid composition, which were altered in diabetic rats, reverted back
      to nearly normal with yacon treatment. CONCLUSIONS: These results indicate that
      yacon root flour is a potential diet supplement with high in vivo antioxidant
      activity.

PMID- 25853967
TI  - Aldose reductase and protein tyrosine phosphatase 1B inhibitory active compounds
      from Syzygium cumini seeds.
AB  - CONTEXT: Syzygium cumini (L.) Skeels (Myrtaceae), commonly known as jamun, is an
      Indian plant, traditionally well known for its medicinal properties including
      antidiabetic activity. OBJECTIVE: To isolate the antidiabetic compounds from
      Syzygium cumini seeds and evaluate their activity using aldose reductase (AR) and
      protein-tyrosine phosphatase 1B (PTP1B) inhibition assays. MATERIALS AND METHODS:
      The dried seeds were extracted with methanol and partitioned with ethyl acetate,
      butanol, and water. The extracts were screened for antidiabetic activity at a
      concentration of 100 ug/mL using in vitro AR and PTP 1B inhibition assays.
      RESULTS AND DISCUSSION: The highly enriched fractions obtained from broad ethyl
      acetate fraction yielded maslinic acid (1), 5-(hydroxymethyl) furfural (2),
      gallic acid (3), valoneic acid dilactone (4), rubuphenol (5), and ellagic acid
      (6). Structures were elucidated by (1)H-NMR and (13)C-NMR. The initial ethyl
      acetate fraction showed AR inhibitory activity with the IC50 value of 2.50 MUg/mL
      and PTP1B enzyme inhibition with the IC50 value of 26.36 MUg/mL. Compounds 3, 4,
      5, and 6 were found to inhibit AR with IC50 values of 0.77, 0.075, 0.165, and
      0.12 MUg/mL while the compounds 4, 5, and 6 inhibited PTP1B with IC50 values of
      9.37, 28.14, and 25.96 MUg/mL, respectively. CONCLUSION: The results of this
      study demonstrate that the isolated constituents show promising in vitro
      antidiabetic activity and, therefore, can be candidates for in vivo biological
      screening using relevant models to ascertain their antidiabetic activity.

PMID- 25853968
TI  - Protective effect of Convolvulus pluricaulis standardized extract and its
      fractions against 3-nitropropionic acid-induced neurotoxicity in rats.
AB  - CONTEXT: Convolvulus pluricaulis Chois. (Convolvulaceae), a well-known Ayurvedic
      "Medhya Rasayana" (nervine tonic), is extensively used for different central
      nervous system (CNS) disorders. OBJECTIVE: The objective of this study was to
      evaluate the protective effect of standardized hydro-methanol extract of C.
      pluricaulis (CPE) and its fractions, namely ethyl acetate (EAE), butanol (BE),
      and aqueous (AE), against 3-nitropropionic acid (3-NP) induced neurotoxicity in
      rats. MATERIALS AND METHODS: The extract of the whole plant was standardized on
      the basis of scopoletin content (0.014%) using thin layer chromatography
      densitometric analysis. CPE (100 and 200 mg/kg) and its fractions, namely EAE (15
      and 30 mg/kg), BE (25 and 50 mg/kg), and AE (50 and 100 mg/kg) were administered
      orally for 20 d. Their protective effect against 3-NP (10 mg/kg, i.p. for 14 d)
      was assessed by the effect on various behavioral parameters, namely body weight,
      locomotor activity, grip strength, gait pattern, and the effect on cognitive
      dysfunction. Biochemical parameters for oxidative damage were also assessed in
      the striatum and cortex regions of the brain. RESULTS: Administration of 3-NP
      induced HD-like symptoms that were indicated by reduced body weight, locomotor
      activity, memory, grip strength, and oxidative defense. CPE (200 mg/kg), EAE (30
      mg/kg), and BE (50 mg/kg) significantly (p < 0.001) attenuated 3-NP induced
      reduction in locomotor activity, grip strength, memory, body weight, and
      oxidative defense in comparison with 3-NP-treated animals on 10 and 15 d.
      CONCLUSION: The present study suggested that CPE has a protective action against
      3-NP-induced neurotoxicity and can be further explored for its efficacy against
      Huntington's disease.

PMID- 25853969
TI  - Transdermal absorption enhancing effect of the essential oil of Rosmarinus
      officinalis on percutaneous absorption of Na diclofenac from topical gel.
AB  - CONTEXT: Rosemary essential oil has been used topically for several purposes
      (analgesic, anti acne, and anti-inflammatory) in Iranian traditional medicine.
      OBJECTIVES: This investigation aimed to study the effect of essential oil of
      Rosmarinus officinalis L. (Lamiaceae) on the transdermal absorption of Na
      diclofenac from topical gel. MATERIAL AND METHODS: Diclofenac sodium topical gel
      was prepared with HPMC K4M and Carbopol 934P as a gelling agent, and several
      vehicles. The most stable gel was chosen and enhancing effects of the essential
      oil with different concentrations (0.1, 0.5, and 1.0% w/w) on the permeation of
      diclofenac were evaluated. The anti-nociceptive effect of preparations was
      evaluated based on the formalin and tail flick tests in mice. RESULTS: The major
      constituents of the essential oil were 1,8-cineol (15.96%), alpha-pinene
      (13.38%), camphor (7.87%), bornyl acetate (6.54%), verbenone (5.82%), borneol
      (5.23%), camphene (4.96%), and (E)-caryophyllene (3.8%). Topical diclofenac
      containing 0.5% essential oil showed more analgesic effect after 25, 30, and 35
      min (p < 0.001) than the reference drug in the tail flick test. The analgesic
      effect of preparation containing 1% essential oil was more than reference gel
      after 15 min (p < 0.05). This difference was observed after 20, 25, 30, 35, and
      40 min (p < 0.001) too. Rosemary essential oil 1% promoted analgesic effect of
      drug in comparison with diclofenac gel in the formalin early phase (p < 0.05).
      The enhancing effect of rosemary was observed in 0.5 and 1% concentration (p <
      0.05 and p < 0.001, respectively) in the late phase. CONCLUSION: This study
      proved the enhancing effect of 0.5 and 1% of rosemary essential oil on diclofenac
      percutaneous absorption.

PMID- 25853970
TI  - Anticancer effect of 2,7-dihydroxy-3-methylanthraquinone on human gastric cancer
      SGC-7901 cells in vitro and in vivo.
AB  - CONTEXT: 2,7-Dihydroxy-3-methylanthraquinone (DDMN) is reported to have a
      remarkable anticancer activity against gastric cancer SGC-7901 cells. OBJECTIVE:
      The objective of this study is to study the anticancer effect and mechanism of
      DDMN on SGC-7901 cells. MATERIALS AND METHODS: The MTT assay was used to
      determine the effect of DDMN on cell viability of SGC-7901 cells, and the
      cytotoxic effect was evaluated by the IC50 value. After treatment with different
      doses of DDMN (10, 20, and 40 MUM) for 48 h, flow cytometry was used to
      investigate the apoptosis of SGC-7901 cells induced by DDMN. Further, western
      blotting was performed to study anticancer mechanism by assaying apoptosis
      related proteins containing Mcl-1, Bcl-xl, Bcl-2, Bax, Bak, Bad, cytochrome c,
      caspase-3, and caspase-9. Finally, xenograft assay was used to further evaluate
      the effect of DDMN on SGC-7901 cells by determining body weight of nude mice,
      tumor volumes, and apoptosis-related proteins. RESULTS: These results suggest
      that DDMN can significantly inhibit (IC50 value = 20.92 MUM) the proliferation of
      SGC-7901 cells and induce apoptosis of SGC-7901 cells demonstrated by flow
      cytometry analysis. Additionally, the results of western blotting indicated that
      DDMN can suppress the expression of anti-apoptotic proteins Bcl-xl and Bcl-2,
      increase the expression of pro-apoptotic proteins Bax, Bad (40 MUM), caspase-3
      and caspase-9, and evidently promote the release of cytochrome c from the
      mitochondria to the cytoplasm. The xenograft assay further confirmed that DDMN
      had significant anticancer effects on SGC-7901 cells. CONCLUSION: DDMN had
      significant anticancer effect on SGC-7901 cells in vitro and in vivo related to
      mitochondria-mediated apoptosis.

PMID- 25853972
TI  - Stepwise high-throughput virtual screening of Rho kinase inhibitors from natural
      product library and potential therapeutics for pulmonary hypertension.
AB  - CONTEXT: Pulmonary hypertension (PH) is a devastating disease characterized by
      progressive elevation of pulmonary arterial pressure and vascular resistance due
      to pulmonary vasoconstriction and vessel remodeling. The activation of RhoA/Rho
      kinase (ROCK) pathway plays a central role in the pathologic progression of PH
      and thus the Rho kinase, an essential effector of the ROCK pathway, is considered
      as a potential therapeutic target to attenuate PH. OBJECTIVE: In the current
      study, a synthetic pipeline is used to discover new potent Rho inhibitors from
      various natural products. MATERIALS AND METHODS: In the pipeline, the stepwise
      high-throughput virtual screening, quantitative structure-activity relationship
      (QSAR)-based rescoring, and kinase assay were integrated. The screening was
      performed against a structurally diverse, drug-like natural product library, from
      which six identified compounds were tested to determine their inhibitory
      potencies agonist Rho by using a standard kinase assay protocol. RESULTS: With
      this scheme, we successfully identified two potent Rho inhibitors, namely
      phloretin and baicalein, with activity values of IC50 = 0.22 and 0.95 MUM,
      respectively. DISCUSSION AND CONCLUSION: Structural examination suggested that
      complicated networks of non-bonded interactions such as hydrogen bonding,
      hydrophobic forces, and van der Waals contacts across the complex interfaces of
      Rho kinase are formed with the screened compounds.

PMID- 25853971
TI  - The protective effect of atractylenolide I on systemic inflammation in the mouse
      model of sepsis created by cecal ligation and puncture.
AB  - CONTEXT: Atractylenolide I (AT-I), an active compound isolated from Atractylodes
      macrocephala Koidz (Compositae), shows several pharmacological activities.
      OBJECTIVE: Our present study is designed to investigate the protective effect of
      AT-I on systemic inflammation in the mouse model of sepsis created by cecal
      ligation and puncture (CLP), and explore the possible mechanism. MATERIALS AND
      METHODS: Sepsis mouse model was established by CLP, and the tested dosages of AT
      I were 10, 20, and 40 mg/kg (ip). Pro-inflammatory cytokines in serum (TNF-alpha,
      IL-1beta and IL-6) were determined by the ELISA method; serum lipopolysaccharide
      (LPS) level was measured by the Limulus Amebocyte Lysate (LAL) test; white blood
      cells (WBC) were counted by Blood cell analyzer; contents of alanine transaminase
      (ALT), aspartate transarninase (AST), creatinine (Cre), and blood urea nitrogen
      (BUN) in serum were determined by automatic biochemistry analyzer. For survival
      rate tests, CLP mice were observed within 7 days, and body temperature was
      measured at 0, 4, 8, 12, 24, 48 and 72 h after surgery. RESULTS: Our results
      indicated that AT-I significantly increased the survival rate of mice with sepsis
      (p < 0.05), whereas the WBCs and levels of LPS, pro-inflammatory cytokines (TNF
      alpha, IL-1beta and IL-6), ALT, AST, Cre, and BUN decreased significantly after
      treatment with AT-I (p < 0.05). CONCLUSION: In conclusion, the AT-I ameliorates
      sepsis syndrome by reduction of pro-inflammatory cytokines and LPS, and provides
      an improvement in liver and kidney functions.

PMID- 25853973
TI  - Co-administration of adjuvants along with Moringa oleifera attenuates beryllium
      induced oxidative stress and histopathological alterations in rats.
AB  - CONTEXT: Moringa oleifera Lam. (Moringaceae) is a rich source of antioxidants.
      All parts of the plant are medicinally important and have been used as
      traditional medicine for a variety of human ailments in India. OBJECTIVE:
      Therapeutic efficacy of adjuvants with M. oleifera (MO) root extract was
      investigated against beryllium-induced oxidative stress. MATERIALS AND METHODS:
      Hydroalcoholic (50% v/v) root extract of M. oleifera (150 mg/kg, p.o.) alone and
      combinations of M. oleifera with either piperine (2.5 mg/kg, p.o.) or curcumin
      (5.0 mg/kg, p.o.) daily for 1 week were administered in experimental rats against
      beryllium toxicity (1.0 mg/kg, i.p. daily for 5 weeks). Oxidative stress
      parameters including blood sugar, G-6-Pase in liver, and DNA damage were
      analyzed. Histopathological changes in liver and kidney were also observed.
      RESULTS: Beryllium enhanced lipid peroxidation (LPO), depleted reduced
      glutathione (GSH) and antioxidant enzymes activities, decreased blood sugar and G
      6-Pase activity, and did not damage DNA. Histologically, liver was observed with
      structural loss and disintegration of hepatocytes, heavy vacuolation in
      hepatocytes, and kidney was observed with constriction of glomeruli and
      hypertrophy in epithelial cells of uriniferous tubules. Therapy of M. oleifera
      with piperine was effective; however, combination of M. oleifera with curcumin
      showed better therapeutic effect by reduction of LPO, elevated GSH level,
      maintained antioxidant enzymes activities, restored blood sugar, and G-6-Pase
      activity in liver together with almost normal histoarchitecture of liver and
      kidney. DISCUSSION AND CONCLUSION: Curcumin enhanced therapeutic efficacy of M.
      oleifera root extract and showed better antioxidant potential against beryllium
      toxicity.

PMID- 25853974
TI  - Antibacterial, antioxidant, and topical anti-inflammatory activities of Bergia
      ammannioides: A wound-healing plant.
AB  - CONTEXT: Despite the traditional use of Bergia ammannioides Henye ex Roth.
      (Elatinaceae) for the treatment of wounds in India, there is a scarcity of
      scientific data supporting this use. OBJECTIVE: The objective of this study is to
      assess wound-healing potentiality of the plant, to study pharmacological
      activities that may contribute in eliminating wound complications, and to
      investigate the biologically active fractions. MATERIAL AND METHODS: The
      ethanolic extract (EtOH) of the aerial parts was fractionated to obtain n-hexane
      (HxFr), chloroform (ClFr), ethyl acetate (EtFr), and n-butanol (BuOH) fractions.
      EtOH and its fractions were formulated in strength of 5 and 10% w/w ointment and
      tested for wound-healing activity using the excision model. The topical anti
      inflammatory, in vitro antioxidant, and antibacterial activities were evaluated.
      HxFr and EtFr were chemically investigated to isolate their constituents.
      RESULTS: Application of EtOH, HxFr, and EtFr (10% w/w ointments) leads to 71.77,
      85.62, and 81.29% healing of the wounds with an increase in the collagen content.
      HxFr had the strongest anti-inflammatory (64.5% potency relative to Voltaren(r))
      and antibacterial activity (MIC = 104 MUg/ml against Staphylococcus aureus),
      while EtFr showed the strongest antioxidant activity against DPPH, ABTS(*+), and
      super oxide radical with an IC50 value of 10.25 +/- 0.01, 66.09 +/- 0.76, and
      167.33 +/- 0.91 ug/ml, respectively. beta-Sitosterol, lupeol, cyclolaudenol, and
      cycloartenol were isolated from HxFr. Quercetin, ellagic acid, kaempferol-3-O
      alpha-l-rhamnoside, and quercetin-3-O-alpha-l-rhamnoside were isolated from EtFr.
      DISCUSSION AND CONCLUSION: Our study presents scientific evidence for the
      efficacy of B. ammannioides in enhancing wound healing, and the first isolation
      of cyclolaudenol and cycloartenol from Bergia.

PMID- 25853975
TI  - The effect of lipoic acid on acrylamide-induced neuropathy in rats with reference
      to biochemical, hematological, and behavioral alterations.
AB  - CONTEXT: Acrylamide (ACR) is a well-known neurotoxicant and carcinogenic agent
      which poses a greater risk for human and animal health. OBJECTIVE: The present
      study evaluates the beneficial effects of alpha-lipoic acid (LA) on ACR-induced
      neuropathy. MATERIALS AND METHODS: A total of 40 male rats were divided into four
      groups: a placebo group; LA-treated group, administered orally 1% (w/w) LA mixed
      with diet; ACR-treated group, given 0.05% (w/v) ACR dissolved in drinking water;
      and LA + ACR-treated group, given LA 1% 7 d before and along with ACR 0.05% for
      21 d. After 28 d, blood samples were collected, the rats were decapitated, and
      the tissues were excised for the measurement of brain biomarkers, antioxidant
      status, and hematological analysis. Also, the gait score of rats was evaluated.
      RESULTS: ACR-exposed rats exhibited abnormal gait deficits with significant (p <
      0.05) decline in acetylcholine esterase (AChE) and creatine kinase in serum and
      brain tissues, respectively. However, the lactate dehydrogenase activity was
      increased in serum by 123%, although it decreased in brain tissues by -74%. ACR
      significantly (p < 0.05) increased the malondialdehyde level by 273% with
      subsequent depletion of glutathione S-transferase (GST), glutathione peroxidase
      (GPx), and glutathione reductase (GR) activities and reduced the glutathione
      (GSH) level in brain tissue. Interestingly, LA significantly (p < 0.05) improved
      brain enzymatic biomarkers, attenuated lipid peroxidation (LPO), and increased
      antioxidant activities compared with the ACR-treated group. DISCUSSION AND
      CONCLUSION: These results suggested that LA may have a role in the management of
      ACR-induced oxidative stress in brain tissues through its antioxidant activity,
      attenuation of LPO, and improvement of brain biomarkers.

PMID- 25853976
TI  - Effects of Heliopsis longipes ethanolic extract on mouse spermatozoa in vitro.
AB  - CONTEXT: Heliopsis longipes (A. Gray) Blake (Asteraceae), a plant native to
      Mexico, is used in traditional medicine as analgesic and microbicide. The main
      component in the H. longipes ethanolic extract (HLEE) is affinin, as determined
      by HPLC/UV-visible and NMR measurement. To date, there is no documented evidence
      on the spermicidal activity of this extract. OBJECTIVE: The objective of this
      study was to assess in vitro the effectiveness of HLEE as spermicide. MATERIALS
      AND METHODS: The spermicidal activity of HLEE was evaluated by the Sander-Cramer
      assay. Spermatozoa were incubated for 20 s with HLEE in concentrations ranging
      from 75 to 2000 ug/mL to determine the minimum effective concentration (MEC)
      value. The 50% effective concentration (EC50) of HLEE was estimated by assaying
      serial dilutions from the MEC. Additionally, sperms were incubated with 125, 250,
      or 500 ug/mL of HLEE to evaluate the viability and the integrity of sperm
      membrane. Lipid peroxidation was assessed by the thiobarbituric acid reactive
      substances assay. RESULTS: HLEE caused an inhibition of 100% in spermatozoa
      motility at a MEC value of 2000 ug/mL; the EC50 value was 125 ug/mL.
      Additionally, exposure to HLEE at 125, 250, or 500 ug/mL for 30 min decreased
      sperm viability to 27%, 8%, and 2% of the control value, respectively, and
      significantly increased the percentage of sperms with structurally disorganized
      membrane. HLEE also increased significantly the level of lipid peroxidation in
      sperms with respect to controls. DISCUSSION AND CONCLUSION: The results
      demonstrate the spermicidal activity of HLEE in vitro and suggest that this
      action is caused by oxidative damage and alterations in the spermatozoal
      membrane.

PMID- 25853977
TI  - The physicochemical properties of geraniin, a potential antihyperglycemic agent.
AB  - CONTEXT: Natural products play a vital role in the discovery of leads for novel
      pharmacologically active drugs. Geraniin (GE) was identified as the major
      compound in the rind of Nephelium lappaceum L. (Sapindaceae), while ellagic and
      gallic acids have been shown to be its main metabolites. GE and its metabolites
      possess a range of bioactive properties including being an anti-infective,
      anticarcinogenic, antihyperglycemic, and antihypertensive. OBJECTIVE: GE and its
      metabolites were investigated to establish its gastrointestinal absorption and
      physicochemical properties. MATERIALS AND METHODS: GE was purified from N.
      lappaceum rind extract using reverse-phase C18 column chromatography.
      Lipophilicity (log P) was determined using the 1-octanol/water shake-flask
      method. Equilibrium solubility of GE and its metabolites (20 mg) was determined
      in water and four biorelevant media: simulated gastric, simulated intestinal,
      fasted state-simulated intestinal, and fed state-simulated intestinal after 72 h.
      RESULTS AND DISCUSSION: The purification yield was 10.8%; where a 97-99% pure GE
      was obtained. Log P values for GE, ellagic, and gallic acids were established as 
      0.73 +/- 0.17, 0.11 +/- 0.06, and 0.71 +/- 0.21, respectively, establishing them
      as polar compounds. All three compounds were found to exhibit poor solubility in
      gastric (0.61-8.10 mg/mL) but good solubility in intestinal fluids (3.59-14.32
      mg/mL). CONCLUSION: The above results indicate that the compounds have limited
      gastrointestinal absorption due to its polarities. To consider these compounds as
      oral drug candidates, formulation strategies are being developed.

PMID- 25853978
TI  - Detection of plant-based adulterants in turmeric powder using DNA barcoding.
AB  - CONTEXT: In its powdered form, turmeric [Curcuma longa L. (Zingiberaceae)], a
      spice of medical importance, is often adulterated lowering its quality.
      OBJECTIVE: The study sought to detect plant-based adulterants in traded turmeric
      powder using DNA barcoding. MATERIALS AND METHODS: Accessions of Curcuma longa
      L., Curcuma zedoaria Rosc. (Zingiberaceae), and cassava starch served as
      reference samples. Three barcoding loci, namely ITS, rbcL, and matK, were used
      for PCR amplification of the reference samples and commercial samples
      representing 10 different companies. PCR success rate, sequencing efficiency,
      occurrence of SNPs, and BLAST analysis were used to assess the potential of the
      barcoding loci in authenticating the traded samples of turmeric. RESULTS: The PCR
      and sequencing success of the loci rbcL and ITS were found to be 100%, whereas
      matK showed no amplification. ITS proved to be the ideal locus because it showed
      greater variability than rbcL in discriminating the Curcuma species. The presence
      of C. zedoaria could be detected in one of the samples whereas cassava starch,
      wheat, barley, and rye in other two samples although the label claimed nothing
      other than turmeric powder in the samples. DISCUSSION AND CONCLUSION: Unlabeled
      materials in turmeric powder are considered as adulterants or fillers, added to
      increase the bulk weight and starch content of the commodity for economic gains.
      These adulterants pose potential health hazards to consumers who are allergic to
      these plants, lowering the product's medicinal value and belying the claim that
      the product is gluten free. The study proved DNA barcoding as an efficient tool
      for testing the integrity and the authenticity of commercial products of
      turmeric.

PMID- 25853979
TI  - Capillary pCO2 helps distinguishing idiopathic pulmonary arterial hypertension
      from pulmonary hypertension due to heart failure with preserved ejection
      fraction.
AB  - RATIONALE: The demographics of patients with idiopathic pulmonary arterial
      hypertension (IPAH) are changing and this diagnosis is increasingly being made in
      older patients. However, diagnostic misclassifications are common as it may be
      difficult to differentiate between IPAH and pulmonary hypertension due to heart
      failure with preserved ejection fraction (PH-HFpEF). We investigated the
      hypothesis that the capillary pCO2 (pcCO2) may help distinguishing between
      idiopathic pulmonary arterial hypertension (IPAH) and pulmonary hypertension due
      to heart failure with preserved ejection fraction (PH-HFpEF). METHODS: In a cross
      sectional study, we retrospectively assessed pcCO2 levels (obtained from
      arterialized capillary blood at the time of diagnosis) from patients with IPAH or
      PH-HFpEF, respectively. Receiver operated characteristics (ROC) were used to
      determine the pcCO2 level providing the best discrimination between these two
      conditions. PcCO2 values were considered helpful if they were associated with a
      negative predictive value >0.9 to excluded either IPAH or PH-HFpEF. RESULTS: The
      study enrolled 185 patients, 99 with IPAH (74% female; age 47 +/- 17 years; body
      mass index 26 +/- 5 kg/m2, PAPm 53 +/- 12 mmHg, PAWP 8 +/- 3 mmHg), and 86 with
      PH-HFpEF (64% female; age 69 +/- 10 years; body mass index 30 +/- 6 kg/m2, PAPm
      47 +/- 10 mmHg, PAWP 21 +/- 5 mmHg). PcCO2 at time of diagnosis was 33 +/- 4 mmHg
      in the IPAH group and 40 +/- 5 mmHg in the PH-HFpEF group (p < 0.001),
      respectively. According to ROC analysis, a pcCO2 of 36 mmHg was the best
      discriminator between both entities with an area under curve of 0.87 (p < 0.001).
      The likelihood of PH-HFpEF was <10% in patients with a PcCO2 < 34 mmHg, whereas
      the likelihood of IPAH was <10% in patients with a PcCO2 > 41 mmHg. CONCLUSIONS:
      PcCO2 levels were significantly lower in IPAH compared to PH-HFpEF and may
      provide useful information in differentiating between both conditions.

PMID- 25853980
TI  - Neuron-to-neuron alpha-synuclein propagation in vivo is independent of neuronal
      injury.
AB  - INTRODUCTION: Interneuronal propagation of alpha-synuclein has been demonstrated
      in a variety of experimental models and may be involved in disease progression
      during the course of human synucleinopathies. The aim of this study was to assess
      the role that neuronal injury or, vice versa, cell integrity could have in
      facilitating interneuronal alpha-synuclein transfer and consequent protein
      spreading in an in vivo animal model. RESULTS: Viral vectors carrying the DNA for
      human alpha-synuclein were injected into the rat vagus nerve to trigger protein
      overexpression in the medulla oblongata and consequent spreading of human alpha
      synuclein toward pons, midbrain and forebrain. Two vector preparations sharing
      the same viral construct were manufactured using identical procedures with the
      exception of methods for their purification. They were also injected at
      concentrations that induced comparable levels of alpha-synuclein
      transduction/overexpression in the medulla oblongata. alpha-Synuclein load was
      associated with damage (at 6 weeks post injection) and death (at 12 weeks) of
      medullary neurons after treatment with only one of the two vector preparations.
      Of note, neuronal injury and degeneration was accompanied by a substantial
      reduction of caudo-rostral propagation of human alpha-synuclein. CONCLUSIONS:
      Interneuronal alpha-synuclein transfer, which underlies protein spreading from
      the medulla oblongata to more rostral brain regions in this rat model, is not a
      mere consequence of passive release from damaged or dead neurons. Neuronal injury
      and degeneration did not exacerbate alpha-synuclein propagation. In fact, data
      suggest that cell-to-cell passage of alpha-synuclein may be particularly
      efficient between intact, relatively healthy neurons.

PMID- 25853981
TI  - Organic Dyes Incorporating the Dithieno[3,2-f:2',3'-h]quinoxaline Moiety for Dye
      Sensitized Solar Cells.
AB  - New donor-acceptor'-acceptor-type sensitizers (QBT dyes), comprising arylamine as
      the electron donor, dithieno[3,2-f:2',3'-h]quinoxaline as the internal acceptor,
      and 2-cyanoacrylic acid as both the acceptor and anchor, have been synthesized.
      The QBT dyes have broad absorption spectra covering the range of lambda=368-487
      nm with a highest molar extinction coefficient of up to approximately 40 000 M(
      1)  cm(-1) . The light-to-electricity conversion efficiencies of the dye
      sensitized solar cells (DSSCs) fabricated from the dyes range from 6.11 to 7.59 %
      under simulated AM 1.5 G illumination. Upon addition of a threefold concentration
      of chenodeoxycholic acid as the co-adsorbent, the best performance cell has a
      power-conversion efficiency of 8.41 %, which is higher than that of the N719
      based standard DSSC (8.27 %).

PMID- 25853983
TI  - The first zinc phosphite with remarkable structural and functional
      transformations.
AB  - A new zinc phosphite exhibited remarkable structural transformations upon heat
      stimulation to convert into a dehydrated form (NCU-2a) and a new structure, NCU
      2b. The gas adsorption properties of the materials as well as the luminescence
      properties of LED devices fabricated using these materials were also
      investigated. 

PMID- 25853982
TI  - Large cell neuroendocrine carcinoma of the lung presenting as pseudoachalasia: a
      case report.
AB  - INTRODUCTION: Pseudoachalasia is a rare disease that accounts for only a small
      percentage of patients with dysphagia. Neuroendocrine tumors are rare
      malignancies that most commonly originate within the gastrointestinal tract, with
      the next most common site being the lungs. Esophageal neuroendocrine tumors are
      the least common site within the gastrointestinal tract. Pseudoachalasia can be
      secondary to a malignant process within the body. Its typical characteristic in
      elderly patients is a short duration of symptoms with substantial weight loss.
      CASE PRESENTATION: A 68-year-old woman presented with worsening dysphagia that
      had started six months after the resection of a large cell neuroendocrine
      carcinoma of the lung in 2011. An extensive work-up in 2012, including
      esophagogastroduodenoscopy, chest computed tomography and positron emission
      tomography, was unremarkable. Esophageal manometries revealed findings
      characteristic of achalasia. A repeat esophagogastroduodenoscopy in January of
      2014 revealed a nearly circumferential ulcerated, fungating mass in her distal
      esophagus. Biopsy results confirming a recurrence of her large cell
      neuroendocrine carcinoma. CONCLUSION: We report a case of pseudoachalasia due to
      metastatic large cell neuroendocrine carcinoma of the lung. Our patient had an
      exceptionally prolonged duration of symptoms preceding the local esophageal
      recurrence, which was eventually revealed via endoscopy.

PMID- 25853984
TI  - Reprocessable squeezing electrode fabrication of olive-like Fe/Co/O
      nanoparticle@three dimensional nitrogen-doped reduced graphene oxides for high
      performance lithium batteries.
AB  - A one step in situ synthesis approach is developed to construct 3D nitrogen-doped
      reduced graphene oxides, in which olive-like multi-component metal oxides are
      homogeneously dispersed. The novel hybrid nanoarchitecture shows some particular
      properties derived from synergistic effects. The size of Fe/Co/O oxides is
      reduced and better controlled compared to that of individual oxides due to mutual
      dispersant interactions. Furthermore, the positive synergistic interaction
      between heterogeneous oxides and graphene nanosheets has effective control on the
      particle size and dispersion of nanoparticles. Taking advantage of the
      flexibility and the cohesiveness of graphene nanosheets, the obtained composite
      can be directly processed into a binder-free electrode through a unique time
      saving "squeezing" process. The obtained electrode possesses a reprocessable
      feature, which provides possibilities for convenient storage and quick
      fabrication at any time and presents attractive electrochemical performance of
      robust long-term capability retention (562 mA h g(-1) after 300 cycles at 10 A g(
      1)) and superior rate performances (1162 mA h g(-1) at 0.5 A g(-1), 737 mA h g(
      1) at 5 A g(-1), and 585 mA h g(-1) at 10 A g(-1)). 

PMID- 25853985
TI  - Cell surface-based sensing with metallic nanoparticles.
AB  - Metallic nanoparticles provide versatile scaffolds for biosensing applications.
      In this review, we focus on the use of metallic nanoparticles for cell surface
      sensings. Examples of the use of both specific recognition and array-based
      "chemical nose" approaches to cell surface sensing will be discussed. 

PMID- 25853986
TI  - Nanoparticle-lipid bilayer interactions studied with lipid bilayer arrays.
AB  - The widespread environmental presence and commercial use of nanoparticles have
      raised significant health concerns as a result of many in vitro and in vivo
      assays indicating toxicity of a wide range of nanoparticle species. Many of these
      assays have identified the ability of nanoparticles to damage cell membranes.
      These interactions can be studied in detail using artificial lipid bilayers,
      which can provide insight into the nature of the particle-membrane interaction
      through variation of membrane and solution properties not possible with cell
      based assays. However, the scope of these studies can be limited because of the
      low throughput characteristic of lipid bilayer platforms. We have recently
      described an easy to use, parallel lipid bilayer platform which we have used to
      electrically investigate the activity of 60 nm diameter amine and carboxyl
      modified polystyrene nanoparticles (NH2-NP and COOH-NP) with over 1000 lipid
      bilayers while varying lipid composition, bilayer charge, ionic strength, pH,
      voltage, serum, particle concentration, and particle charge. Our results confirm
      recent studies finding activity of NH2-NP but not COOH-NP. Detailed analysis
      shows that NH2-NP formed pores 0.3-2.3 nm in radius, dependent on bilayer and
      solution composition. These interactions appear to be electrostatic, as they are
      regulated by NH2-NP surface charge, solution ionic strength, and bilayer charge.
      The ability to rapidly measure a large number of nanoparticle and membrane
      parameters indicates strong potential of this bilayer array platform for
      additional nanoparticle bilayer studies. 

PMID- 25853988
TI  - Luminescence studies on green emitting InGaN/GaN MQWs implanted with nitrogen.
AB  - We studied the optical properties of metalorganic chemical vapour deposited
      (MOCVD) InGaN/GaN multiple quantum wells (MQW) subjected to nitrogen (N)
      implantation and post-growth annealing treatments. The optical characterization
      was carried out by means of temperature and excitation density-dependent steady
      state photoluminescence (PL) spectroscopy, supplemented by room temperature PL
      excitation (PLE) and PL lifetime (PLL) measurements. The as-grown and as
      implanted samples were found to exhibit a single green emission band attributed
      to localized excitons in the QW, although the N implantation leads to a strong
      reduction of the PL intensity. The green band was found to be surprisingly stable
      on annealing up to 1400 degrees C. A broad blue band dominates the low
      temperature PL after thermal annealing in both samples. This band is more intense
      for the implanted sample, suggesting that defects generated by N implantation,
      likely related to the diffusion/segregation of indium (In), have been optically
      activated by the thermal treatment. 

PMID- 25853989
TI  - Are Anti-inflammatory Therapies Viable Treatments for Psychiatric Disorders?:
      Where the Rubber Meets the Road.

PMID- 25853990
TI  - Painting biological low-frequency vibrational modes from small peptides to
      proteins.
AB  - Protein low-frequency vibrational modes are an important portion of a proteins'
      dynamical repertoire. Yet, it is notoriously difficult to isolate specific
      vibrational features in the spectra of proteins. Given an appropriately chosen
      model peptide, and using different experimental conditions, we can simplify the
      system and gain useful insights into the protein vibrational properties.
      Combining neutron scattering, depolarized light scattering, and molecular
      dynamics simulations, we analyse the low frequency vibrations of biological
      molecules, comparing the results from a small globular protein, lysozyme, and an
      amphiphilic peptide, NALMA, both in solution and in powder states. Lysozyme and
      NALMA present similar spectral features in the frequency range between 1 and 10
      THz. With the aid of MD simulations, we assign the spectral features to methyl
      groups' librations (1-5 THz) and hindered torsions (5-10 THz) in NALMA. Our data
      also show that, while proteins display boson peak vibrations in both powder and
      solution forms, NALMA exhibits boson peak vibrations in powder form only. This
      provides insight into the nature of this feature, suggesting a connection of BP
      collective motions to a characteristic length scale of heterogeneities present in
      the system. These results provide context for the use of model peptide systems to
      study protein dynamics; demonstrating both their utility, and the great care that
      has to be used in extrapolating results observed in powder to solutions. 

PMID- 25853991
TI  - Diuretic and Natriuretic Effects of Dipeptidyl Peptidase-4 Inhibitor
      Teneligliptin: The Contribution of Glucagon-like Peptide-1.
AB  - Glucagon-like peptide-1 receptor (GLP-1R) agonists and dipeptidyl peptidase-4
      (DPP-4) inhibitors are antidiabetic agents; however, their mechanisms of action
      are different. GLP-1R and DPP-4 are also expressed in the renal proximal tubular
      brush border, where they regulate Na reabsorption. We investigated whether the
      DPP-4 inhibitor, teneligliptin, has diuretic and natriuretic effects and whether
      these are associated with the stimulation of the GLP-1R in rats. Oral
      administration of teneligliptin resulted in a reduction of plasma DPP-4 activity
      over 6 hours, as well as an induction of diuresis and natriuresis. Although
      teneligliptin did not change the increase in blood glucose levels by glucose
      loading, percentage of urine volume and Na/K ratio with teneligliptin to vehicle
      were augmented by glucose loading. Peak levels of plasma GLP-1 did not change
      after oral administration of teneligliptin when glucose was not loaded but
      increased at least 2-fold with glucose loading. Furthermore, the natriuretic
      effect of teneligliptin was inhibited by the GLP-1R antagonist, exendin9-39,
      whereas the diuresis was not affected. These results suggest that the mechanism
      of natriuresis was different from that of diuresis, and the natriuresis is
      associated with the stimulation of GLP-1R. There may be mechanistic differences
      in DPP-4 inhibition between diuresis and natriuresis. 

PMID- 25853992
TI  - Third-hand Smoke: Impact on Hemostasis and Thrombogenesis.
AB  - Cigarette smoking is a major risk factor for acute coronary thrombosis. In fact,
      both active/first-hand smoke and passive/second-hand smoke exposure are known to
      increase the risk of coronary thrombosis. Although recently a new risk has been
      identified and termed third-hand smoke (THS), which is the residual tobacco smoke
      contaminant that remains after a cigarette is extinguished, it remains to be
      determined whether it can also enhance the risk of thrombogenesis, much like
      first-hand smoke and second-hand smoke. Therefore, the present studies
      investigated the impact of THS exposure in the context of platelet biology and
      related disease states. It was found that THS-exposed mice exhibited an enhanced
      platelet aggregation and secretion responses as well as enhanced integrin GPIIb
      IIIa activation. Furthermore, it was found that THS exposure shortens the tail
      bleeding time and the occlusion time in a model of thrombosis. Thus, our data
      demonstrate for the first time (at least in mice) that THS exposure increases the
      risk of thrombosis-based disease states, which is attributed, at least in part,
      to their hyperactive platelets. 

PMID- 25853993
TI  - Comparative Characterization of Human and Equine Mesenchymal Stromal Cells: A
      Basis for Translational Studies in the Equine Model.
AB  - Multipotent mesenchymal stromal cells (MSCs) have gained tremendous attention as
      potential therapeutic agents for the treatment of orthopedic diseases. Promising
      results have been obtained after application of MSCs for treatment of tendon and
      joint disease in the equine model, making it appear favorable to use these
      results as a basis for the translational process of the therapy. However, while
      the horse is considered a highly suitable model for orthopedic diseases,
      knowledge is lacking regarding the level of analogy of equine MSCs and their
      human counterparts. Therefore, the aim of this study was to assess the properties
      of human and equine adipose- and tendon-derived MSCs in a direct comparison.
      Basic properties of human and equine MSCs from both tissues were similar. The
      cells expressed CD29, CD44, CD90, and CD105 and lacked expression of CD73, CD14,
      CD34, CD45, CD79alpha, and MCHII/HLA-DR. No significant differences were found
      between proliferation potential of human and equine MSCs in early passages, but
      recovery of nucleated cells after tissue digestion as well as proliferation in
      later passages was higher in equine samples (p < 0.01). All samples showed a good
      migration capacity and multilineage differentiation potential. However, while
      osteogenic differentiation was achieved in all equine samples, it was only
      evident in five out of nine human tendon-derived samples. Human MSCs further
      showed a higher expression of collagen IIIA1 and tenascin-C, but lower expression
      of decorin and scleraxis (p < 0.01). Although revealing some potentially relevant
      differences, the study demonstrates a high level of analogy between human and
      equine MSCs, providing a basis for translational research in the equine model
      according to the guidelines issued by the authorities.

PMID- 25853994
TI  - A fluorescent histone deacetylase (HDAC) inhibitor for cellular imaging.
AB  - Fluorescence microscopy studies using 4-morpholinoscriptaid (4MS) demonstrated
      rapid cellular uptake of this scriptaid analogue into the cytoplasm but no
      nuclear penetration. As 4MS and scriptaid have the same in vitro activity against
      HDACs and KASUMI-1 cells; 4MS exemplifies a rational approach to subtly modify
      'profluorogenic' substrates for intracellular studies.

PMID- 25853995
TI  - Influence of electron storing, transferring and shuttling assets of reduced
      graphene oxide at the interfacial copper doped TiO2 p-n heterojunction for
      increased hydrogen production.
AB  - Herein we report simple, low-cost and scalable preparation of reduced graphene
      oxide (rGO) supported surfactant-free Cu2O-TiO2 nanocomposite photocatalysts by
      an ultrasound assisted wet impregnation method. Unlike the conventional
      preparation techniques, simultaneous reduction of Cu(2+) (in the precursor) to
      Cu(+) (Cu2O), and graphene oxide (GO) to rGO is achieved by an ultrasonic method
      without the addition of any external reducing agent; this is ascertained by X-ray
      diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) analyses. UV-visible
      diffused reflectance spectroscopy (DRS) studies (Tauc plots) provide evidence for
      the loading of Cu2O tailoring the optical band gap of the photocatalyst from 3.21
      eV to 2.87 eV. The photoreactivity of the as-prepared Cu2O-TiO2/rGO samples is
      determined via H2 evolution from water in the presence of glycerol as a hole
      (h(+)) scavenger under visible light irradiation. Very interestingly, the
      addition of rGO augments the carrier mobility at the Cu2O-TiO2 p-n
      heterojunction, which is evidenced by the significantly reduced luminescence
      intensity of the Cu2O-TiO2/rGO photocatalyst. Hence rGO astonishingly enhances
      the photocatalytic activity compared with pristine TiO2 nanoparticles (NPs) and
      Cu2O-TiO2, by factors of ~14 and ~7, respectively. A maximum H2 production rate
      of 110 968 MUmol h(-1) gcat(-1) is obtained with a 1.0% Cu and 3.0% GO
      photocatalyst composition; this is significantly higher than previously reported
      graphene based photocatalysts. Additionally, the present H2 production rate is
      much higher than those of precious/noble metal (especially Pt) assisted (as co
      catalysts) graphene based photocatalysts. Moreover, to the best of our knowledge,
      this is the highest H2 production rate (110 968 MUmol h(-1) gcat(-1)) achieved by
      a graphene based photocatalyst through the splitting of water under visible light
      irradiation. 

PMID- 25853996
TI  - Peculiar pressure effect on Poisson ratio of graphone as a strain damper.
AB  - Hydrogenation is an effective way to modify the electronic and magnetic
      properties of graphene. The semi-hydrogenated graphene, known as "graphone", has
      promising applications in nanoelectronics including field-effect transistors.
      However, the elastic limit of this two-dimensional material remains unknown
      despite its importance in applications as well as strain engineering to tailor
      functions and properties. Here we report using first-principles calculations an
      abnormal increase in the Poisson ratio of graphone in response to an increase in
      pressure. This peculiar behavior is proposed to originate from the asymmetry of
      hydrogenation and could be used to design a nanodevice of strain damper to reduce
      harmful strains in graphene-based nanoelectronics. 

PMID- 25853997
TI  - Temperature and host cell-dependent changes in virulence of Chlamydia pneumoniae
      CWL029 in an optimized mouse infection model.
AB  - The obligate intracellular bacterium Chlamydia (C.) pneumoniae causes respiratory
      infections and is associated with vascular diseases. To elucidate how temperature
      and host cells used for propagation alter chlamydial virulence, C. pneumoniae
      CWL0129 (Cpn) was cultured at 35 or 37 degrees C in two different cell lines and
      then applied to mice. These mice infected with differentially propagated
      chlamydiae showed differences in clinical score, body weight and inflammatory
      cytokines in the lung. Our study demonstrates that Cpn cultured at 37 degrees C
      in hamster fibroblast BHK-21 are able to colonize the mouse lung faster and
      better, and induce stronger symptoms and cytokine induction than bacteria
      cultured at 35 degrees C. The temperature-triggered virulence alteration could
      not be observed for Cpn propagated in HeLa cells and was independent of host cell
      protein synthesis. Transcriptome analysis did not reveal temperature-induced
      effects on chlamydial gene expression, suggesting that the observed virulence
      changes are regulated on a different, so far unknown level. Preculture close to
      the central body temperature of its warm-blooded human or murine host might
      'prepare' Cpn for subsequent in vivo infection. Our identification of culture
      dependent virulence alteration helps to establish an optimized mouse lung
      infection model for Cpn and provides the basis to further unravel the molecular
      mechanisms underlying chlamydial pathogenicity. 

PMID- 25853998
TI  - Chlamydia psittaci: update on an underestimated zoonotic agent.
AB  - Chlamydia (C.) psittaci is an economically relevant pathogen in poultry and pet
      birds, where it causes psittacosis/ornithosis, and also a human pathogen causing
      atypical pneumonia after zoonotic transmission. Despite its well-documented
      prevalence, the agent has received less attention by researchers than other
      Chlamydia spp. in the last decades. In the present paper, we review recently
      published data on C. psittaci infection and attempt to single out characteristic
      features distinguishing it from related chlamydial agents. It is remarkable that
      C. psittaci is particularly efficient in disseminating in the host organism
      causing systemic disease, which occasionally can take a fulminant course. At the
      cellular level, the pathogen's broad host cell spectrum (from epithelial cells to
      macrophages), its rapid entry and fast replication, proficient use of
      intracellular transport routes to mitochondria and the Golgi apparatus, the
      pronounced physical association of chlamydial inclusions with energy-providing
      cell compartments, as well as the subversive regulation of host cell survival
      during productive and persistent states facilitate the characteristic efficient
      growth and successful host-to-host spread of C. psittaci. At the molecular level,
      the pathogen was shown to upregulate essential chlamydial genes when facing the
      host immune response. We hypothesize that this capacity, in concert with
      expression of specific effectors of the type III secretion system and efficient
      suppression of selected host defense signals, contributes to successful
      establishment of the infection in the host. Concerning the immunology of host
      pathogen interactions, C. psittaci has been shown to distinguish itself by coping
      more efficiently than other chlamydiae with pro-inflammatory mediators during
      early host response, which can, to some extent, explain the effective evasion and
      adaptation strategies of this bacterium. We conclude that thorough analysis of
      the large number of whole-genome sequences already available will be essential to
      identify genetic markers of the species-specific features and trigger more in
      depth studies in cellular and animal models to address such vital topics as
      treatment and vaccination.

PMID- 25853999
TI  - Two more species of Chlamydia-does it make a difference?
AB  - The recent description of Chlamydia (C.) avium and C. gallinacea as new species
      of the reunited genus Chlamydia can be expected to have implications on the
      perception of avian chlamydiosis. We discuss possible effects on epidemiology,
      diagnosis and our understanding of aetiopathogenesis resulting from this
      discovery. 

PMID- 25854000
TI  - Twenty years of research into Chlamydia-like organisms: a revolution in our
      understanding of the biology and pathogenicity of members of the phylum
      Chlamydiae.
AB  - Chlamydiae are obligate intracellular bacteria that share a unique but remarkably
      conserved biphasic developmental cycle that relies on a eukaryotic host cell for
      survival. Although the phylum was originally thought to only contain one family,
      the Chlamydiaceae, a total of nine families are now recognized. These so-called
      Chlamydia-like organisms (CLOs) are also referred to as 'environmental
      chlamydiae', as many were initially isolated from environmental sources. However,
      these organisms are also emerging pathogens, as many, such as Parachlamydia sp.,
      Simkania sp. and Waddlia sp., have been associated with human disease, and
      others, such as Piscichlamydia sp. and Parilichlamydia sp., have been documented
      in association with diseases in animals. Their strict intracellular nature and
      the requirement for cell culture have been a confounding factor in characterizing
      the biology and pathogenicity of CLOs. Nevertheless, the genomes of seven CLO
      species have now been sequenced, providing new information on their potential
      ability to adapt to a wide range of hosts. As new isolation and diagnostic
      methods advance, we are able to further explore the richness of this phylum with
      further research likely to help define the true pathogenic potential of the CLOs
      while also providing insight into the origins of the 'traditional' chlamydiae. 

PMID- 25854001
TI  - Prevalence and diversity of Chlamydiales in Swiss ruminant farms.
AB  - Chlamydia and Chlamydia-related bacteria are known to infect various organisms
      and may cause a wide range of diseases, especially in ruminants. To gain insight
      into the prevalence of these bacteria in the ruminant environment, we applied a
      pan-Chlamydiales PCR followed by sequencing to 72 ruminant environmental samples
      from water, feed bunks and floors. Chlamydiales from four family-level lineages
      were detected indicating a high biodiversity of Chlamydiales in ruminant farms.
      Parachlamydiaceae were detected in all three types of environmental samples and
      was the most abundant family-level taxon (60%). In contrast, only one bacterium
      from each of the following family-level lineages was identified: Chlamydiaceae,
      Criblamydiaceae and Simkaniaceae. The observed high prevalence of
      Parachlamydiaceae in water samples may suggest water as the main source of
      contamination for ruminants as well as their environment due to spoilage. The
      absence of reported infections in the investigated ruminant farms might indicate
      that either detected Chlamydiales are of reduced pathogenicity or infective doses
      have not been reached. 

PMID- 25854003
TI  - Chlamydia psittaci in ducks: a hidden health risk for poultry workers.
AB  - Chlamydia psittaci is a zoonotic pathogen associated primarily with avian
      chlamydiosis also referred as psittacosis. Human psittacosis can lead to severe
      cases of respiratory disease. The mule duck is one of the main bird hybrids
      associated with human cases of psittacosis in France. In order to better
      understand the epidemiology of avian chlamydiosis, monitoring studies were
      performed in both breeder flocks and mule duck flocks. Surveys conducted in one
      professional duck bredding organization revealed little shedding in breeder
      flocks, whereas heavy but asymptomatic C. psittaci shedding was observed in most
      of the mule duck flocks, mostly when birds were reared in open range conditions
      on farms. Human cases of psittacosis linked to duck breeder flocks and their
      progeny led to detection of heavy shedders in all the suspected flocks despite no
      birds showing clinical signs. Offspring of one of the infected female flocks was
      analyzed and also proved to be infected by C. psittaci. Field studies suggest
      that C. psittaci infections in duck farms involve horizontal and probably
      vertical transmission but that the environment also plays an important role in
      maintaining infection on farms. In the light of the widespread occurrence of C.
      psittaci on duck farms, it has become urgent to clearly identify sources of
      contamination in order to take appropriate field management measures to minimize
      worker exposure. 

PMID- 25854002
TI  - Infection with Chlamydia pneumoniae as a cause of coronary heart disease: the
      hypothesis is still untested.

PMID- 25854004
TI  - A mouse model for Chlamydia suis genital infection.
AB  - A mouse model for Chlamydia suis genital infection was developed. Ninety-nine
      mice were randomly divided into three groups and intravaginally inoculated with
      chlamydia: 45 mice (group 1) received C. suis purified elementary bodies (EBs),
      27 (group 2) were inoculated with C. trachomatis genotype E EBs and 27 mice
      (group 3) with C. trachomatis genotype F EBs. Additionally, 10 mice were used as
      a negative control. At seven days post-infection (dpi) secretory anti-C. suis IgA
      were recovered from vaginal swabs of all C. suis inoculated mice. Chlamydia suis
      was isolated from 93, 84, 71 and 33% vaginal swabs at 3, 5, 7 and 12 dpi.
      Chlamydia trachomatis genotype E and F were isolated from 100% vaginal swabs up
      to 7 dpi and from 61 and 72%, respectively, at 12 dpi. Viable C. suis and C.
      trachomatis organisms were isolated from uterus and tubes up to 16 and 28 dpi,
      respectively. The results of the present study show the susceptibility of mice to
      intravaginal inoculation with C. suis. A more rapid course and resolution of C.
      suis infection, in comparison to C. trachomatis, was highlighted. The mouse model
      could be useful for comparative investigations involving C. suis and C.
      trachomatis species. 

PMID- 25854007
TI  - Editorial: new insights into Chlamydia: from genes to diseases in humans and
      animals.

PMID- 25854008
TI  - Patients and technology:  improving access to  healthcare.

PMID- 25854005
TI  - Andrographolide inhibits intracellular Chlamydia trachomatis multiplication and
      reduces secretion of proinflammatory mediators produced by human epithelial
      cells.
AB  - Chlamydia trachomatis is the most common sexually transmitted bacterial disease
      worldwide. Untreated C. trachomatis infections may cause inflammation and
      ultimately damage tissues. Here, we evaluated the ability of Andrographolide
      (Andro), a natural diterpenoid lactone component of Andrographis paniculata, to
      inhibit C. trachomatis infection in cultured human cervical epithelial cells. We
      found that Andro exposure inhibited C. trachomatis growth in a dose- and time
      dependent manner. The greatest inhibitory effect was observed when exponentially
      growing C. trachomatis was exposed to Andro. Electron micrographs demonstrated
      the accumulation of unusual, structurally deficient chlamydial organisms,
      correlated with a decrease in levels of OmcB expressed at the late stage of
      infection. Additionally, Andro significantly reduced the secretion of
      interleukin6, CXCL8 and interferon-gamma-induced protein10 produced by host cells
      infected with C. trachomatis. These results indicate the efficacy of Andro to
      perturb C. trachomatis transition from the metabolically active reticulate body
      to the infectious elementary body and concurrently reduce the production of a
      proinflammatory mediator by epithelial cells in vitro. Further dissection of
      Andro's anti-Chlamydia action may provide identification of novel therapeutic
      targets. 

PMID- 25854009
TI  - Fixed drug eruption due  to dexketoprofen.

PMID- 25854010
TI  - Sputum neutrophilia and severe persistent asthmatics.

PMID- 25854006
TI  - NOD1 in contrast to NOD2 functional polymorphism influence Chlamydia trachomatis
      infection and the risk of tubal factor infertility.
AB  - Intracellular pattern-recognition receptors NOD1 and NOD2 are capable of sensing
      common structural units of bacterial walls. Recognition triggers specific immune
      signalling pathways and leads to pro-inflammatory cytokine upregulation and
      adequate immune response. We investigated whether two functional polymorphisms in
      NOD1 and NOD2 exert an effect on susceptibility to (STD patients) and severity of
      (female patients visiting the fertility clinic) Chlamydia trachomatis infection
      in 807 Dutch Caucasian women. A significant association of the NOD1 +32656 GG
      insertion variant with protection against infection with C. trachomatis has been
      detected [p: 0.0057; OR: 0.52]. When comparing C. trachomatis-positive women
      without symptoms to C. trachomatis-positive women with symptoms, and to C.
      trachomatis-positive women with TFI, we observed an increasing trend in carriage
      of the GG allele [Ptrend: 0.0003]. NOD2 1007fs failed to reveal an association.
      We hypothesize that the underlying mechanism might be a functional effect of the
      GG insertion on IFN-beta-dependent regulation of immune response in the genital
      tract. The research is part of an ongoing effort of identifying key polymorphisms
      that determine the risk of TFI and effectively translating them into the clinical
      setting for the purpose of optimizing diagnostic management of women at risk for
      developing TFI. 

PMID- 25854011
TI  - [Compairison between western and Chinese acupuncture and its enlightenment].
AB  - With the wide application of acupuncture in the world, the research results of
      neurosciences have made scientific approval on some of efficacy and mechanism of
      acupuncture, and the concept of western medical acupuricture (WMA) is gradually
      developed. During the spread of Chinese acupuncture into western countries, WMA
      is an adaptive improvement when facing basic theories of western medicine
      including anatomy, physiology and pathology as well as evidence-based medicine
      system. WMA which is based on theory of muscle trigger point has obvious efficacy
      on muscular fasciae pain, which attracted wide attention. But when Chinese
      acupuncture spreads into western world, the theories of Chinese acupuncture such
      as meridian and specificity of acupoint are questioned due to the results of
      western clinical study. In this paper, the origin, theory development,
      stimulating location and method, and categories of diseases of WMA are compared
      with Chinese acupuncture, and the enlightenment of this difference on Chinese
      acupuncture research is analyzed.

PMID- 25854012
TI  - [Improvement of the oocyte quality with electroacupuncture in infertility
      patients of kidney deficiency pattern].
AB  - OBJECTIVE: To explore the impact and effect mechanism of electroacupuncture (EA)
      on oocyte quali ty in the patients with infertility of kidney deficiency pattern.
      METHODS: Sixty-six cases differentiated as kidney de ficiency and with in vitro
      fertilization-embryo transplantation (IVF-ET), aged fromnt 35 to 42 years were
      rando- mized into an observation group and a control group, 33 cases in each one.
      The IVF-ET therapy of the long proto- col with gonadotrophin releasing hormone
      agonist was adopted in the two groups. In the observation group. on the 5th day
      of menstruation in IVF cycle, EA was applied to Sanyinjiao (SP 6). Zigong (EX CA
      1), Zhongji (CV 3) and Guanyuan (CV 4). In the control group, the sham
      acupuncture was applied to the same acupoints. The treatment was given once every
      two days till the date of egg collection and the needles were retained for 30 min
      each time. The change in the score of kidney deficiency syndrome, the high
      quality oocyte rate, the high-quality embryo rate and clinical pregnant rate were
      observed in the two groups. The levels of insulin-like growth factor-i (IGF-1)
      and IGF-2 in follicular fluid and the serum beta-endorphin beta-EP) on the date
      of egg collection and the correlation with oocyte quality were compared bIetween
      the two groups. RESULTS: 1) In the observation group, the kidney deficiency
      syndrome score after treatment was reduced apparently as compared with that
      before treatment (P<0. 05), the score after treatment in the observation group
      was reduced much more apparently as compared with the control group (P<0.05). 2)
      The high-quality egg rate and the high-quality embryo rate in the observation
      group were both higher than those in the control group [81.3% (161/198) vs 57.6%
      (98/170), 59.8% (58/97) vs 37.7% (26/69), both P<0.05]. 3) Compared with the
      control group. the levels of IGF-1 and IGF-2 in follicular fluid and serum beta
      EP on the day of egg collection were all increased obviously in the observation
      group (all P<0. 05). 4) The levels of IGF-1 and IGF-2 in follicular fluid and
      serum beta-EP presented the linear positive correlation with the high-quality egg
      rate. CONCLUSION: EA effectively improves the expressions of IGF in follicular
      fluid and serum beta-EP, increases the high-quality egg rate and high-quality
      embryo rate and relieves the symptoms of kidney deficiency.

PMID- 25854013
TI  - [Infertility in polycystic ovary syndrome treated with acupuncture and
      clomiphene: a randomized controlled trial].
AB  - OBJECTIVE: To explore the best therapy for infertility caused by polycystic ovary
      syndrome (PCOS). METHODS: One hundred and twenty patients were randomized into
      three groups, a clomi-phene group (group A), an acupuncture-moxibustion + Chinese
      medicine group (group B) and a clomiphene + acupuncture-moxibustion+ Chinese
      medicine group (group C), 40 cases in each one. In the group A, since the 5th day
      of menstruation, clomiphene was prescribed for oral administration. In the group
      B, on the 5th day of menstruation, warm needling therapy was applied at Zhongji
      (CV 3), Guanyuan (CV 4), Guilai (ST 29), etc. Additionally, the Chinese herbal
      medication for tonifying the kidney and activating blood circulation was
      provided. In the group C, the therapy as the group B was combined on the basis of
      the treatment as the group A. The treatment lasted continuously for 3 menstrual
      cycles. The endometrial thickness, endometrial type and cervical mucus score on
      human chorionic gon adotropin (HCG) day, and ovulatory cycle rate, clinical
      pregnancy rate and abortion rate after treatment were observed in the patients of
      the three groups. RESULTS: 1) HCG day cervical mucus score, endometrial thickness
      and endometrial morphology (A type rate): the results in the group C were better
      than those in the group A (all P<0.01); the results in the group B were better
      than those in the group A (all P<0.05). The difference in the endometrial
      thickness was not significant in comparison between the group C and the group B
      (P>0.05). The cervical mucus score and endometrial morphology (A type rate) in
      the group C were better than those in the group B (both P<0.05). 2) The ovulatory
      cycle rates in the group A and group (C were higher than that in the group B
      (both P<0.05), the pregnancy rate in the group C was higher than that in the
      other groups (both P<0.05), and the early abortion rate in the group C was lower
      than that in the group A and group B (both P<0.01). 3) Follicle diameter from 18
      mm to 20 mm and endometrial thickness: the differences were not significant
      between the normal pregnancy patients and the early abortion patients (both
      P>0.05). The endometrial morphology A type rate in the normal pregnancy patients
      was higher than that in the early abortion patients (P<0.05). CONCLUSION: The
      combined therapy of acupuncture, herbal medicine and clomiphene improves the
      pregnancy rate and reduces early abortion rate by effectively improving HCG day
      cervical mucus, endometrial thickness and morphology. The efficacy is apparently
      superior to the simple medication with clomiphene and the combined application of
      acupuncture and herbal medicine.

PMID- 25854014
TI  - [Efficacy on post-stroke depression treated with acupuncture at the acupoints
      based on ziwuliuzhu and prozac].
AB  - OBJECTIVE: To observe the effects on post-stroke depression treated with
      acupuncture at the acu points based on ziwuliuzhu (the midnight-noon ebb-flow
      theory). METHODS: Ninety-three patients were randomized into a comprehensive
      group, a ziwuliuzhu group and a prozac group, 31 cases in each group. In the
      ziwuliuzhu group, acupuncture was applied to the acupoints based on ziwuliuzhu,
      once a day, 5 times in a week. In the prozac group, fluoxertine hydrochloride
      (prozac) was prescribed for oral administration, once a day, 20 mg each time. In
      the comprehensive group, acupuncture based on ziwuliuzhu combined with the oral
      administration of prozac were adopted and the treatment frequency was the same as
      the ziwuliuzhu group and the prozac group. The 4-week treatment was taken as one
      session in the three groups and 6 sessions were required totally. The clinical
      efficacy and the Hamilton depression rating scale (HAMD) score and the adverse
      reaction were compared among the 3 groups. RESULTS: The total effective rate was
      96.8% (30/31) in the comprehensive group, better than 83.9% (26/31) in the
      ziwuliuzhu group and 80. 6% (25/31) in the prozac group (both P<0.05). In 4, 12
      and 24 weeks of treatment, HAMD score was lower significantly than that before
      the treatment in the three groups (all P<0.05), and the score in the
      comprehensive group at each time point after treatment was lower than the other
      two groups (all P<0.05). In 4 and 12 weeks of treatment, there were not different
      significantly between the ziwuliuzhu group and the prozac group (both P>0.05). In
      24 weeks of treatment, HAMD score in the ziwuliuzhu group was lower than that in
      the prozac group (P<0.05). For the adverse reaction, there were 2 cases in the
      comprehensive group, 6 cases in the prozac group and 0 case in the ziwzuliuzhu
      group. CONCLUSION: The comprehensive therapy of acupuncture at the acupoints
      based on ziwuliuzhu and oral administration of prozac is superior to either the
      simple oral administration of prozac or the ziwuliuzhu acu-puncture in terms of
      clinical efficacy and the improvements in depressive state. Regarding the
      clinical efficacy, the impact of simple ziwuliuzhu acupuncture is not different
      significantly as compared with the simple oral administration of prozac, but it
      is better than the simple oral administration of prozac in terms of the long-term
      HAMD score and safety.

PMID- 25854015
TI  - [Clinical observasion of acupuncture in patients with depression and its impact
      on serum 5-HT].
AB  - OBJECTIVE: To observe the clinical effect of acupuncture for depression and to
      discuss its impact on the content of 5-HT in patients with depression. METHODS:
      Eighty patients with depression were randomly divided into an acupuncture group
      and a western medication group,40 cases in each one. Acupuncture was applied in
      the acupuncture group,Siman(KI 14),Shenshu(BL 23),Guanyuan(CV 4),Dazhui(GV
      14),Yinlingquan(SP 9), Zusanli(ST 36),Taichong(LR 3),Yanglingquan(GB 34) and
      Jingming(BL 1) were selected, the intensive moxibustion was applied at
      G(uanyuan(CV 4). Fluoxetine was treated with oral administration in the western
      medication group. The treatments of six weeks were required in each group. The
      Hamilton depression rating scale (HAMD) was applied to evaluate efficacy and
      serum 5-HT was detected before and after treatment in the two groups. RESULTS:
      After treatment,the scores of HAMD were decreased obviously in the two groups
      compared with those before treatment (scores in the acupuncture group: 24. 48 +/-
      0. 28 vs 8. 95 +/- 2. 24; scores in the western medication group: 24. 14+/-0. 24
      vs 10. 29+/-1. 30),and the differences were statistically significant (both P<0.
      05). Between the two groups,the scores of HAMD in the acupuncture group at the
      end of the lst,2nd,4th,6th weeks were superior to those in the western medication
      group (all P<0. 05). The content of serum 5-HT after treatment was increased
      markedly compared with that before treatment [the content in the acupuncture
      group: (26. 21 2. 36)pg/mL vs (52. 07 +/- 0. 56)pg/mL, the content in the western
      medication group:(26. 26+/-2. 31)pg/mL vs (51. 70+/-0. 52)pg/ mL, both P<0. 05].
      But there was no statistic significance between the two groups(P >0.05).
      CONCLUSION: The efficacy of acupuncture for depression is superior to that of
      western medication with fluoxetine.

PMID- 25854016
TI  - [Timeliness law on the immediate analgesia on acute migraine treated with
      electroacupuncture at shaoyang meridian points].
AB  - OBJECTIVE: To observe the differences in timely effectiveness of immediate
      analgesia on acute migraine between electroacupuncture (EA) at shaoyang meridian
      points and non-meridian points. METHODS: The randomized controlled trial method
      was adopted. One hundred and ten cases of acute migraine were randomized into two
      groups. 55 cases in each one. In the observation group, EA was applied to Fengchi
      (GB 20), Waiguan (TE 5), etc. In the control group. EA was applied to non
      meridian points. Only one treatment was given, and the nee dies were retained for
      30 min in the two groups. Separately. at 10 time points, named before
      acupuncture, in 5 min, 10 min. 20 min and 30 min (at the moment of needle
      removal), 1 h, 2 h, 4 h, 6 h and 8 h after acupuncture, the pain intensity
      numerical rating scale (PI-NRS) was adopted to evaluate the pain severity and the
      adverse reac tion was recorded. RESULTS: (1) The effective rate of imnmediate
      analgesia was 87. 3% (48/55) in the observation group. significantly higher than
      52.7% (29/55) in the control group (P<0.01). (2) NRS of each group was re duced
      at each time point, from 5 min to 8 h after acupuncture (all P<0.01). (3) NRS
      score at 30 min after acu puncture in the control group was obviously lower than
      that in the observation group (P<0.05), but the scores in 2 h, 4 h, 6 h and 8 h
      after acupuncture in the observation group were lower apparently than those in
      the control group (all P<0. 01). The differences in the scores in 5 min, 10 min,
      20 min and 1 h after acupuncture were not significant (all P>0. 05). (4) For the
      reducing amplitude of NRS score at the same time point after acupuncture, the
      results in 20 min, 30 min and 1 h in the control group were higher apparently
      than those in the observation group (all P<0. 05). But, in 2 h, 4 h, 6 h and 8 h,
      the results in the observation group were higher apparently than those in the
      control group (all F<0.05). The differences in 5 min and 10 min after acupuncture
      were not significant (both P>0. 05). (5) In 24 h after acupuncture, the
      recurrence rate of migraine was 12. 7% (7/55) in the observation group, which was
      lower obviously than 34. 5% (19/55) in the control group (P<0. 05). The adverse
      reaction was not found in the two groups. CONCLUSION: EA at the shaoyang meridian
      points achieves the definite immediate analgesia effect on acute migraine and
      presents the time effectiveness of analgesia.

PMID- 25854017
TI  - [Effects of acupuncture intervention at different stages on urinary function
      reconstruction of neurogenic bladder after spinal cord injury].
AB  - OBJECTIVE: To explore the effects of early intervention of acupuncture on urinary
      function reconstruction of neurogenic bladder after spinal cord injury, so as to
      find the optimal treatment timing of acupuncture. METHODS: Fifty-three patients
      of neurogenic bladder after spinal cord injury were randomly divided into a prior
      to-catheter group (25 cases) and a posterior-to-catheter group (28 cases). For
      the prior-to-catheter group, one week before the removal of catheter, acupoints
      on the abdomen and back such as Guanyuan (CV 4), Zhongji (CV 3), Baliao
      (Shangliao (BL 31), Ciliao (BL 32), Zhongliao (BL 33), Xialiao (BL 34), Jiaji (EX
      B 2) and acupoints at distal end such as Zusanli (ST 36) and Sanyinjiao (SP 6)
      were selected; after the catheter removal, simple method. of water column was
      used to measure bladder capacity pressure to classify the type of bladder, and
      then different acupuncture manipulations were given; intermittent catheterization
      was performed if condition was allowed. The posterior-to-catheter group applied
      identical treatment after removal of catheter as the prior-to-catheter group. The
      treatment was given 5 times per week; after one-month treatment, five aspects
      including the time of first effective urination, time of establishing reflex
      urination, average residual volume of urine, time of residual urine less than 100
      mL and quality of life (QOL) were evaluated. RESULTS: After treatment, the time
      of first effective urination, time of establishing reflex urination, average
      residual volume of urine and time of residual urineless than 100 mL in the prior
      to-catheter group were all superior to those in the posterior-to-catheter group
      (all P<0. 05) ; the score of QOL was improved in two groups after treatment (both
      P<0. 01), but the difference between two groups was not statistically significant
      (P>0. 05); each index of urination function was not significant among patients
      with different injured segments of spinal cord (all P>0. 05). CONCLUSION: The
      early intervention of acupuncture (prior to catheter) has obvious improving
      function on establishing balanced bladder in patients with neurogenic bladder
      after spinal cord injury, which is superior to acupuncture intervention after
      removal of catheter, however, the effects of different injured segments on
      establishing balanced bladder are not different.

PMID- 25854018
TI  - [Case of muscular twitching in the whole body].

PMID- 25854019
TI  - [Efficacy of acupuncture combined with auricular point sticking on the content of
      serum prostaglandin F2alpha, and plasma arginine vasopressin in patients with
      menstrual headache].
AB  - OBJECTIVE: To observe the clinical efficacy of acupuncture combined with
      auricular point sticking for menstrual headache and to discuss its mechanism.
      METHODS: Eighty-five patients with menstrual headache were randomly divided into
      an observation group (43 cases) and a control group (42 cases). The observation
      group was treated with body acupuncture combined with auricular point sticking
      and the control group was treated with flunarizine hydrochloride capsules orally.
      The treatments of 3 menstrual cycles were required. The clinical efficacy was
      observed in the two groups. The content of serum prostaglandin F2alpha,
      (PGF2alpha) and plasma arginine vasopressin (AVP) in the menstrual periods of
      some patients randomly selected in the two groups was tested before and after
      treatment and was compared with that of 20 cases in a normal group. Results The
      total effective rate was 95.4% (41/43) in the observation group which was
      obviously superior to 81.0% (34/42) in the control group (P<0.01). Before
      treatment, the content of serum PGF2alpha and plasma AVP of patients in the two
      groups was higher than that in the normal group (all P<0.01). After treatment,the
      content of serum PGF2alpha and plasma AVP was lower than that before treatment in
      the two groups (P<0.01, P<0.05). The content of serum PGF2alpha in the
      observation group was decreased significantly compared with that in the control
      group (P<0.05) and returned to the level of the normal group. CONCLUSION: Body
      acupuncture combined with auricular point sticking achieves positive efficacy for
      menstrual headache and its mechanism could be related to regulating the abnormal
      levels of serum PGF2alpha and plasma AVP.

PMID- 25854020
TI  - [Clinical controlled trial on infantile Tourette syndrome treated with integrated
      therapy of acupuncture and medicine].
AB  - OBJECTIVE: To compare the difference in the clinical efficacy on infantile
      Tourette syndrome between the integrated therapy of acupuncture and pingganjianpi
      decoction and haloperidol tablets. METHODS: Forty-seven children were randomized
      into an observation group (25 cases) and a control group (22 cases). In the
      observation group, acupuncture was applied to Taichong (LR 3), Baihui (GV 20),
      Zhongwan (CV 12), Zusanli (ST 36), etc. The needles were retained for 30 min.
      Acupuncture was given once a day and there were 5 days at intervals after 10
      times of acupuncture. Additionally, pinggan jianpi decoction was prescribed. In
      the control group, haloperidol tablets were prescribed, starting from the small
      dose, 0. 05 mg/kg per day, twice a day. The treatment of 30 days made one session
      and 3 sessions were required. Yale global tic severity scale (YGTSS) was adopted
      to observe tic time, tic frequency and tic severity score before treatment and in
      30 days, 60 days and 90 days after treatment in the two groups. The efficacy and
      adverse reactions were compared between the two groups. RESULTS: The total
      effective rates were 40. 0% (10/25), 64.0% (16/25) and 76.0% (19/25) in the
      observation group and were 59.1% (13/22), 68.2% (15/22) and 77.3% (17/22) in the
      control group in 30 days, 60 days and 90 days after treatment respectively. The
      effect in 30 days after treatment in the control group was better than that in
      the observation group (P<0. 05). The differences at the other time points were
      not significant between the two groups (all P>0. 05). The tic time, tic frequency
      and tic severity score at the each time point after treatment were reduced
      obviously as compared with those before treatment (all P<0. 05). Each item score
      in the control group was reduced obviously as compared with that in the
      observation group in 30 days after treatment (all P<0. 05). The differences at
      the other time points were not significant between the two groups (all P>0.05).
      The probability of adverse reaction in the observation group was less than that
      in the control group. CONCLUSION: The integrated therapy of acupuncture and
      medicine achieves the similar effect on infantile Tourette syndrome to
      haloperidol tablets and the side effects of it are less.

PMID- 25854021
TI  - [Impacts of electroacupuncture combined with ultraviolet therapy on cytokines of
      herpes zoster at the acute stage in patients].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) combined with
      ultraviolet therapy on herpes zoster at the acute stage and the impacts on serum
      interleukin 2 (IL-2), interleukin 6 (IL-6) and interleukin 10 (IL-10) in the
      patients. METHODS: Thirty-four patients of herpes zoster were randomized into a
      medicine group and a combined therapy group, 17 cases in each one. In the
      medicine group, the intravenous drops with acyclovir injection, muscular
      injection with cobamamide and the topical with acyclovir ointment were applied.
      Additionally, TDP was radiated locally. In the combined therapy group, on the
      basis of the treatment as the medicine group, EA and ultraviolet therapy were
      supplemented. The duration of treatment was 10 days in the two groups. Before and
      after treatment, blister relief, incrustation time and the visible analogue scale
      (VAS) were recorded in the two groups. The clinical efficacy was assessed in the
      two groups and the levels of serum IL-2, IL-6 and IL-10 were determined in the
      two groups. RESULTS: In the combined therapy group, the time of blister relief
      and incrustation was earlier apparently than that in the medicine group (both
      P<0.05). VAS score after treatment were reduced as compared with that before
      treatment in the two groups (both P<0.01), and the reducing amplitude in the
      combined therapy group was larger than that in the medicine group (P<0.01). The
      total effective rate was 94. 1% (16/17) in the combined therapy group, higher
      than 76.4% (13/17) in the medicine group (P<0.05). After treatment, IL-2 levels
      were increased as compared with those before treatment in the two groups (both
      P<0.05), the levels of IL-6 and IL-10 were reduced obviously as compared with
      those before treatment in the two groups (all P<0.01). After treatment, the
      levels of IL-6, IL-10 were reduced much more apparently in the combined therapy
      group as compared with those in the medicine group (both P<0.05). CONCLUSION: EA
      combined with ultraviolet irradiation more rapidly and effectively relief the
      symptoms of herpes zoster, significantly relief pain, shorten the duration of
      sickness, improve the body immunity and reduce nerve injury.

PMID- 25854022
TI  - [Resuscitating needling with scalp acupuncture for 36 cases of intractable
      hiccup].

PMID- 25854023
TI  - [The hidden order in chaos: another interpretation on meridian].
AB  - With chaos theory to analyze human body, and based on fractal theory and existing
      domestic and foreign fractal as well as achievements of biological holographic
      medical practice, the essence of meridians and their evolution were discussed. By
      analog of connection mode between neurons in brain and weakening the exaggerated
      correlation between acupoints, the meridians that had four-dimensional fractal
      structure were proposed, which rediscovered the meaning of the meridians, and
      hoped to provide references for direction of future meridian researches.

PMID- 25854024
TI  - [Core structure of acupoint: interactive network of immune, blood vessel and
      nerve].
AB  - The studying on interrelation and interaction among blood-vessel network, nerve
      network and immune network is considered to be the key to reveal the mechanism of
      acupuncture treatment and the essence of meridians. A strip-like compound
      structure of mast cells, blood vessel and nerve network is observed in acupoint
      area. From its systematics nature and correlation with acupuncture effect and
      meridian phenomena, it is believed that the structure of mast cells, blood vessel
      and nerve network is an interactive system with interrelation and interaction
      among each other, and is an essential site and pivot to produce and transport
      matter, energy and information, and is the core structure of acupoint.

PMID- 25854025
TI  - [Muscular needling with sticking method for 88 cases of shoulder pain].

PMID- 25854026
TI  - [Parametric optimization of electroacupuncture against bone-cancer pain in rats
      and its intervention on mRNA expression of opioid receptor and precursor].
AB  - OBJECTIVE: To observe the intervention of electroacupuncture (EA) with different
      current frequencies and treatment frequencies on pain thresholt in rats with bone
      cancer pain, so as to optimize treatment parameters of EA against bone cancer
      pain; and by measuring gene expression of opioid receptor and precursor in
      different tissues to preliminarily explore the possible mechanism of EA against
      bone cancer pain. METHODS: Ninety healthy female SD rats were randomly divided
      into a control group, a model group, EA groups (6 subgroups according to
      different frequencies) and a sham EA group, ten rats in each one. Rats in the
      control group were injected with 10 uL of amicrobic phosphate buffer solution
      (PBS) into tibial cavity; rats in the remaining groups were injected with Walker
      256 cancer cells to establish model of bone-cancer pain. No treatment was given
      to rats in the control group and model group; rats in the EA groups were treated
      with EA at bilateral "Housanli" (ST 36) and "Genduan" with 3 different current
      frequencies (2 Hz, 100 Hz and 2 Hz/100 Hz), once a day and once every other day,
      30 min per treatment (1mA for 15 min, 2 mA for 15 min); rats in the sham EA group
      were treated with identical acupoints as the EA group, but the acupoints were
      needled subcutaneously and EA was connected with power off. All the treatment was
      given for 14 days. Dynamic plantar aesthesiometer was applied to measure the paw
      withdrawal thresholds (PWTs) of the affected side before the model establishment,
      6d, 8d, 10d, 12d, 14d, 16d, 18d, and 20d after model establishment. The mRNA
      expressions of u-opioid receptor (MOR), kappa-opioid receptor (KOR), delta-opioid
      receptor (DOR), proopiomelanocortin (POMC) and prodynorphin (PDYN) in dorsal root
      ganglion (DRG) and lumbar spinal cord dorsal horn (SCDH) of L4-L6 of the affected
      side were detected by PCR method. RESULTS: There were no differences in PWTs
      among all groups before model establishment (P>0. 05). Each time point after
      model establishment, PWTs in model group were obviously lower than those in the
      control group (all P<0. 01). Compared with the model group, PWTs in each EA
      subgroup were all increased (all P<0.05), but the differences at different time
      points were not significant among EA subgroups (P>0.05). The mRNA expressions of
      MOR, KOR, POMC, and PDYN in L4-L6 DRG in the 2 Hz/100 Hz II group were
      significantly higher than those in model group (P<0. 05, P<0. 01), while the mRNA
      expressions of MOR, KOR, DOR, POMC and PDYN in SCDH were not different compared
      with the model group (P>0. 05). CONCLUSION: EA treatment has obvious analgesic
      effect on bone-cancer pain, however, its effect is not related with current
      frequency and treating frequency. EA against bone-cancer pain may be related with
      increasing the mRNA expression of some peripheral opioid receptors and precursor.

PMID- 25854027
TI  - [Professor HE Tianyou's clinical experience of acupuncture and medicine on
      intractable facial paralysis].
AB  - Professor HE Tianyou's unique understanding and treatment characteristics for
      intractahle facial paralysis are introduced. In clinical practice professor HE
      highly values acupoint selection and manipulation application, and integrates
      Chinese and western medicine to flexibly choose acupoints and formulate
      prescriptions according to syndrome differentiation and location differentiation,
      besides, he creates several specialized manipulation methods including "tug-of
      war opposite acupuncture method" and "tractive flash cupping". Based on
      strengthening body and dredging collaterals. more attention is given on
      stimulation to local paralyzed facial nerves; meanwhile acupuncture and
      medication are combined to improve clinical efficacy. During the treatment, the
      important role of psychological counseling on patient's anxiety is emphasized,
      and comprehensive treatment is given physically and psychologically in order to
      achieve the purpose of total rehabilitation.

PMID- 25854028
TI  - [Acupuncture status analysis in PROSPERO systematic review registry platform].
AB  - By searching the registry information of systematic review regarding acupuncture
      included before March 31, 2014 in PROSPERO systematic review registry platform,
      information in the project plan such as care gories of diseases, interventions,
      research team and the completion status was analyzed to make a comprehensive
      understanding on registry status of acupuncture systematic review in this
      platform. As a result, a total of 52 project plans was finally included. The
      health problem concerned was mainly painrelated diseases, and the interventions
      were mostly simple acupuncture or combination of acupuncture and moxibustion. The
      registered plan participated with Chinese team appeared comparatively late, which
      was featured with fewer independent projects and concentrated research
      organization, so its scientific research advantage in acupuncture did not
      present. In conclusion, it is believed that the consciousness on systematic
      review registry in domestic researchers needs to be improved, and researchers
      might take good advantages of the PROSPERO platform in the future.

PMID- 25854029
TI  - [Application of problem-based learning in teaching practice of Science of
      Meridians and Acupoints].
AB  - Science of Meridians and Acupoints is the bridge between basic medicine and
      clinical medicine of acupuncture and moxibustion. This teaching practice was
      conducted in reference to the teaching mode of problembased learning (PBL), in
      association with the clinical design problems, by taking as the students as the
      role and guided by teachers. In order to stimulate students' active learning
      enthusiasm, the writers implemented the class teaching in views of the typical
      questions of clinical design, presentation of study group, emphasis on drawing
      meridian running courses and acupoint locations, summarization and analysis, as
      well as comprehensive evaluation so that the comprehensive innovative ability of
      students and the teaching quality could be improved.

PMID- 25854030
TI  - [Clinical application and mechanism on the ghost points in the treatment of
      mental diseases].
AB  - In order to explore the clinical application and mechanism of the ghost points in
      the treatment of mental diseases, taking "the ghost points" and "mental diseases"
      as the theme and the key words, the literatures in recent 10 years on the
      treatment of mental diseases with the ghost points were collected from CNKI and
      Wanfang database and analyzed. It is discovered that the ghost points can treat
      schizophrenia, manic-depressive disorder, dementia, stroke, loss of
      consciousness, insomnia. anxiety, depression and hysteria and the efficacy is
      favorable. It is believed that the ghost points act on balancing yin and yang,
      regulating qi and blood, regaining consciousness and tranquilizing the mind and
      they achieve the very excellent effect on mental diseases. At present, the
      reports on this aspect are limited. Hence, it is required to promote the study on
      the clinical application and mechanism of the ghost points so as to enlarge the
      clinical indications of the ghost points and provide the powerful support on
      mechanism for the treatment of mental diseases.

PMID- 25854031
TI  - [Acupuncture mainly at Yuyao (EX-HN 4) and Shangjingming (Extra) for 35 cases of
      oculomotor nerve paralysis].

PMID- 25854032
TI  - [Jingjin and weiqi].
AB  - This is to investigate the relationship between jingjin (the meridian of muscle
      region) and weiqi (the defensive qi) by referring to relevant studies. Jingjin is
      inherent in weiqi and originated from the meridian of foot-taiyang. It receives
      weiqi from the extremities and expands to several meridians of muscle regions.
      Jingjin is where weiqi travels and distributes. When weiqi combines with
      exogenous pathogens, this leads to Bi syndrome of meridian muscle regions. The
      analysis results in that the twelve kinds of Bi syndrome of meridian muscle
      regions belong to the category of Bi syndrome, which is caused by the invasion of
      pathogenic wind-cold-dampness into the muscle. The pathogenesis is related to the
      disorder of weiqi circulation. It is summarized that jingjin is closely related
      to weiqi and reflected in physiology and pathology, etc. The study guides to the
      diagnosis and treatment of jingjin diseases.

PMID- 25854033
TI  - [Case of bronchiectasis in acute stage].

PMID- 25854034
TI  - [From manual workshop to international standard maker: exploration on production
      standard of acupuncture needle by Chengjiang acupuncture school].
AB  - ABSTRACT The exploration course on production standard of acupuncture needle by
      Chengjiang acupuncture school is reviewed in this paper. After new China was
      established, acupuncture needle standard was unified by Mr. CHENG Dan-an, which
      guided Suzhou Hua Erfang (predecessor of Suzhou Medical Supplies Factory) to make
      the quality standards and testing methods of acupuncture needle and improved the
      production process to make the modern acupuncture needle. Based on this, Suzhou
      Medical Supplies Factory followed the time development pace, ac tively introduced
      new technology, carried out technological innovation, and constantly improved the
      level of production technology, as a result, it gradually developed into one of
      the world's largest acupuncture needle production suppliers. Meanwhile, after
      establishing China's first national standard on acupuncture needle (GB 2024
      1980), the Suzhou Medical Supplies Factory took the lead to draft "ISO)
      17218:2014 the disposable use asepsis acupuncture needle", which was officially
      published as an international standard. The Suzhou Medical Supplies Factory
      developed from a manual workshop to an international standard maker.

PMID- 25854035
TI  - [Back fascitis treated with acupuncture at Jinggu (BL 64)].

PMID- 25854036
TI  - [Serving for the longevity and health of people, being the teacher with
      righteousness and charity: professor XIA Shouren, the acupuncture master in
      modern times].
AB  - Professor XIA Shouren is a famous acupuncture master in China and has devoted his
      life to clinical practice, teaching and scientific study of TCM. In his 50 years
      of medical career, he has studied Chinese and western medicine, innovated ancient
      masters' experiences, adhered to the theory of "less but highly-effective
      needling", specified at genjie points and deeply explored the specificity of
      acupoints. Additionally, the acupuncture stfudy has been firstly conducted in the
      diagnosis and treatment of trigeminal neuralgia in China and his own unique
      academic thought has been formed. Professor XIA Shouren makes the contribution to
      the theory, practice and inheritance of acupuncture and moxibustion.

PMID- 25854037
TI  - [Fifty cases of transverse process syndrome of third lumbar vertebra treated by
      acupuncture therapy according to acupotomy].

PMID- 25854038
TI  - [Opinions on electroacupuncture treatment of facial paralysis].

PMID- 25854039
TI  - [Reflections on upper crossed syndrome theory on guidance of acupuncture for
      cervical spondylosis].

PMID- 25854040
TI  - [Development on research of acupuncture effects on microcirculation].
AB  - The Chinese and English published literature regarding the effects of acupuncture
      on microcirculation in recent years were analyzed, and it was found out that the
      theory of TCM meridian had subtle connection with microcirculation on structure
      and function, which could provide a possible breakthrough for the research of
      meridian essence. Acupuncture, through multiple links, multiple paths and
      multiple levels, could regulate microcirculation under physiological or
      pathological condition, which was a bidirectional benign adjustment function, and
      reflected the characteristic of acupoint specificity. Due to many shortcomings in
      the current studies, studies with rigorous design, large sample size and
      multicenter are expected in the further to make a standard systematized research.

PMID- 25854041
TI  - [Venous thromboembolism: the "unknown"].

PMID- 25854042
TI  - [Suspicion of lower limb deep vein thrombosis: update on diagnosis and
      treatment].
AB  - Venous thromboembolism is a frequent disease with an annual incidence of 0.75
      2.69/1000 reaching 2-7/1000 > 70 years. Deep vein thrombosis (DVT) and pulmonary
      embolism are two manifestations of the same underlying disease. Most frequent
      localization of DVT is at lower limbs. The diagnostic workup begins with an
      estimation of DVT risk, a judicious use of D-Dimers, and compression venous
      ultrasound depending on DVT probability. The development of direct oral
      anticoagulants and recent data on interventional DVT treatment, in selected
      cases, have widened the therapeutic spectrum of DVT. The present article aims at
      informing the primary care physician of the optimized workup of patients with
      lower limb suspicion of DVT.

PMID- 25854043
TI  - [Upper extremity deep vein thrombosis: a particular form of venous
      thromboembolism].
AB  - The incidence of upper extremity deep vein thrombosis (UEDVT) is constantly
      increasing due to frequent insertion of intravenous devices for various
      indications. Secondary UEDVT represent more than two thirds of cases. Primary
      UEDVT generally include UEDVT occurring without any triggering factor and UEDVT
      following intense or repeated efforts or in association with the thoracic outlet
      syndrome, with a causative link that may be sometimes very difficult to
      ascertain. As opposed to lower extremity DVT, data remain very scarce and of
      limited quality in this setting. Diagnosis is mainly based on clinical
      probability assessment associated with D-dimer measurement and compression
      ultrasound as first-line imaging. Treatment still consists of therapeutic
      anticoagulation in the vast majority of cases.

PMID- 25854044
TI  - [Catheter-based treatment for acute deep vein thrombosis].
AB  - Nearly half of patients with acute lower limb deep vein thrombosis (DVT) develop
      a post-thrombotic syndrome (PTS). This risk is particularly high in case of
      proximal DVT of the common femoral and iliac vein, the major lower limbs venous
      outflow vessel. Several studies have demonstrated that PTS incidence can be
      reduced with early vein recanalisation. Currently, catheter-based recanalisation
      therapies can be offered to selected patients with acute ilio-femoral deep vein
      thrombosis. Aim of the present article is to summarize current knowledge on these
      catheter-based recanalisation therapies.

PMID- 25854045
TI  - [Non atherosclerotic arterial disease of lower limbs].
AB  - Non atherogenic peripheral arterial diseases must be taken into consideration
      whenever lower limb obstructive peripheral disease is diagnosed. This is
      particularly important in absence of classical cardiovascular risk factors.
      Management and treatment of these non atherogenic arterial disease are dependant
      on their causes.

PMID- 25854046
TI  - [Vascular anomalies].
AB  - Vascular anomalies are rare conditions that could be observed at all ages. They
      are classified, according to their histology, in vascular tumors or vascular
      malformations. The general practitioner plays a significant role in diagnosis and
      patient management, diagnosis being suspected on clinical history. In case of
      vascular anomaly, ultrasound-Doppler assessment is helpful to characterize
      morphologic and hemodynamic changes of the lesion and permits to monitor the
      evolution and to detect complications. Further investigations are often necessary
      prior to multidisciplinary management. In this article, a brief overview of
      vascular anomalies, their multidisciplinary management and the exemple of Klippel
      Trenaunay syndrome are presented.

PMID- 25854047
TI  - [Lymphatic vascular pathologies: contribution of lympho-fluoroscopy].
AB  - If clinical examination has an essential importance in lymphology disorders and
      requires experimented practitioners, lymphoscintigraphy and more recently green
      indocyanine lympho-fluoroscopy constitute precious complementary investigations
      in prevention, diagnosis, and treatment of lymphatic vascular pathologies. The
      lymphoscintigraphy interest lies in qualitative and quantitative analysis of
      macromolecules migration within lymphatic vessels and the deep lymphatic network.
      The lympho-fluoroscopy distinguishes itself from lymphoscintigraphy allowing real
      time superficial lymphatic vessels detailed mapping, gathering important
      information on their contractility, and the presence of compensatory derivations
      to be favored during manual lymphatic drainage to angiologist and
      physiotherapist.

PMID- 25854048
TI  - [Shuttle Challenger disaster: what lessons can be learned for management of
      patients in the operating room?].
AB  - For many years hospitals have been implementing crew resource management (CRM)
      programs, inspired by the aviation industry, in order to improve patient safety.
      However, while contributing to improved patient care, CRM programs are
      controversial because of their limited impact, a decrease in effectiveness over
      time, and the underinvestment by some caregivers. By analyzing the space shuttle
      Challenger accident, the objective of this article is to show the potential
      impact of the professional culture in decision-making processes. In addition, to
      present an approach by cultural factors which are an essential complement to
      current CRM programs in order to enhance the safety of care.

PMID- 25854049
TI  - [Cerebral lymphoma: a classic presentation?].

PMID- 25854050
TI  - [Toxicity of bisphenol A: total European confusion].

PMID- 25854051
TI  - [Patient choice].

PMID- 25854052
TI  - [Reduce the burden of treatment, a step towards a minimally disruptive medicine].

PMID- 25854053
TI  - [Track the alcohol (of caregivers) to the entry of operating rooms].

PMID- 25854054
TI  - [Pancreatic cancer: prediction of risk by measuring blood glucose].

PMID- 25854055
TI  - [At the time, not so long ago, when medicine bewitched].

PMID- 25854057
TI  - [Crisis in the Neuchatel hospital: the mountains revolt].

PMID- 25854056
TI  - [Flu epidemic: HUG, everyone must wear a mask].

PMID- 25854058
TI  - [The strange complicity between memory and forgetting].

PMID- 25854059
TI  - [Systems for local electrophysiological treament based on one-layer carbon
      nanotubes used for studying cell cultures].

PMID- 25854060
TI  - [Determination of optical characteristics of biological scattering medium on the
      basis of the bimodality effect].

PMID- 25854061
TI  - [Mathematical modeling of blood glucose concentration dynamics].

PMID- 25854062
TI  - [New family of pseudorandom hexagonal arrays for coding collimators of ionizing
      radiation].

PMID- 25854063
TI  - [Portable equipment for artificial blood purification].

PMID- 25854064
TI  - [Magnetic field sensors for medical diagnosis].

PMID- 25854065
TI  - [Promising nanomaterials with carbon nanotubes in biomedical applications].

PMID- 25854066
TI  - [The effect of frequency characteristics of oscillatory circuits and power source
      on the efficiency of wireless energy transfer based on inductive coupling].

PMID- 25854067
TI  - [Spectral characteristics of materials based on carbon nanotubes].

PMID- 25854068
TI  - [The investigation of nonlinear properties of carbon nanomaterials under
      threshold limiting of power laser radiation].

PMID- 25854069
TI  - [Development of left ventricular assist devices as the most effective way of
      treatment of acute cardiac insufficiency].

PMID- 25854070
TI  - [Analysis of cardiac rhythm in cardiopulmonary resuscitation].

PMID- 25854071
TI  - [Simulation of changes in the dynamics of blood flow through an implanted axial
      pump].

PMID- 25854072
TI  - [Improvement of legislation basis for occupational risk analysis in occupational
      hygiene and work safety].
AB  - One among priority trendsin health care in Russian Federation and abroad is
      minimization of occupational risks. The authors present evaluation of legislation
      basis for occupational risk analysis. The most promising trend in improvement of
      national legislation is its development on basis of internationally accepted
      documents, that-provides legislation basis for analysis of workers' health risk.
      Findings are that complete evaluation of occupational risk requires combination
      of data on work conditions and data of occupational control, and sometimes--with
      results of special research. Further improvement is needed for justifying
      hygienic norms with applying criteria of allowable risk for workers' health. Now
      development of risk analysis methodology enables quantitative evaluation of
      health risk via mathematic models including those describing risk evolution.

PMID- 25854073
TI  - [Prospects of occupational risk evaluation via modelling methods].
AB  - The article represents methodic approaches that enable quantitative evaluation of
      worker's health risk, forecast of changes in health state. Models application
      proved that integral risk of health disorders in workers exposed to occupational
      factors becomes unacceptable by the age of 45 years, without exposure to the
      factors - by 54 years. At work under existing levels of exposure to occupational
      factors, cardiovascular risk increases with length of service, and by 5 years of
      service, number of additional occupational cases in a studied group of workers
      approaches 11 per year. Solving effectively problems of health risk evaluation,
      evolution models consider specific conditions of workplaces contamination and
      describe influence of variable factors within work conditions on risk of various
      health disorders in dependence on length of service and exposure duration.
      Methodic approaches to health risk evaluation, based on evolution models of
      hazardous effects development under exposure to working environment factors,
      enable to follow dynamics of these effects development on background of natural
      ageing and to forecast health state of human and population under multi
      factorial, multi-exposure load.

PMID- 25854074
TI  - [Problems of occupational fitness conclusion on periodic medical examination].
AB  - Additional examination in Occupational Pathology Center are economic loss both
      for employer and employee, as the employee receives payment for those days when
      in the examination. Analysis of over 600 cases of occupational fitness
      examination in Occupational Pathology Center according to referrals given by
      medical institutions providing periodic medical examination shows that in most
      cases the conclusion was possible during periodic medical examination.
      Difficulties in conclusion on workers' fitness for occupation during periodic
      medical examination, according to our viewpoint, result not from limited
      diagnostic facilities for adequate examination and unfitness disclosure, but from
      lack of information in primary medical documentation and inadequacy of
      occupational factor and work characteristics presented by employer to actual
      working conditions.

PMID- 25854075
TI  - [On work conditions and occupational morbidity in Permsky area].
AB  - Permsky area is one of the most developed regions in Russia and among national
      industrial leaders. Registered level of occupational diseases in Permsky area
      does not correspond to work conditions state in industry. Over last 10 years,
      more than third of workers started having hazardous work conditions, number of
      the workers reduced more than by 200,000. Small-scale and medium business
      employers do not pay proper attention to health care for workers, and the
      situation concerning occupational hygiene in these enterprises deteriorates.
      Workers' health care is topical problem for Permsky area, necessitates systemic
      and complex actions within federal and regional goal-oriented program.

PMID- 25854076
TI  - [Evaluation and prognosis of occupational risk in workers of nonferrous
      metallurgy enterprises].
AB  - The article deals with results of a priori and a posteriori evaluation of
      occupational risk for workers' health. Categories of a priori occupational risk
      for workers are estimated as high to very high (intolerable) risk. Findings are
      that work conditions in nonferrous metallurgy workshop result in upper
      respiratory tract diseases (medium degree of occupational conditionality).
      Increased prevalence of such diseases among the workers is connected with length
      of service. The authors revealed priority factors for occupationally conditioned
      diseases. A promising approach in occupational medicine is creation of methods to
      evaluate and forecast occupational risk, that enable to specify goal parameters
      for prophylactic measures. For example, modelling the risk of occupationally
      conditioned diseases via changes in exposure to occupational factor and length of
      service proved that decrease of chemical concentrations in air of workplace to
      maximally allowable ones lowers risk of respiratory diseases from 14 to 6 cases
      per year, for length of service of 5 years and population risk.

PMID- 25854077
TI  - [Justifying genetic and immune markers of efficiency and sensitivity under
      combined exposure to risk factors in mining industry workers].
AB  - The authors evaluated and justified immunologic and genetic markers under
      combined exposure to risk factors in mining industry workers. Analysis covered
      polymorphism features of 29 genes with variant alleles possibly participating in
      occupationally conditioned diseases formation and serving as sensitivity markers
      of these diseases risk. The genes association selected demonstrates reliably
      changed polymorphism vs. the reference group (SOD2 superoxidedismutase gene,
      ANKK1 dophamine receptor gene, SULT1A1 sulphtransaminase gene, MTHFR methylene
      tetrahydrofolate reductase gene, VEGF endothelial growth factor gene, TNF-alpha
      tumor necrosis factor gene). Under combined exposure to occupational hazards
      (sylvinite dust, noise) in mining industry, this association can serve as
      adequate marking complex of sensitivity to development of occupationally
      conditioned diseases. Increased-production of immune cytokine regulation markers:
      tumor necrosis factor and vascular endothelial growth factor. Genes SOD2, ANKK1,
      SULT1A1, VEGF, TNFalpha are recommended as sensitivity markers, and the coded
      cytokines (tumor necrosis factor and endothelial growth factor) are proposed as
      effect markers in evaluation of health risk for workers in mining industry.

PMID- 25854078
TI  - [Evaluating cytogenetic and hormonal state in female workers of dyeboard industry
      of fabric preparation].
AB  - The article covers data on oxidative activity in cellular DNA, on cytogenetic
      effects, on sexual hormones levels under exposure to chemical hazards in female
      workers of dyeboard fabric preparation industry. Findings are that in such
      occupations as bleacher, mercerization and glazing operator, chemical solutions
      and dyes. supplier, flushing equipment operator demonstrate the highest serum
      levels of manganese, lead, toluene and xylene vs. the reference group parameters
      (1.5-1.8 times) due to occupational hazards. Significant differences were seen
      between the groups of exposed and unexposed workers in parameters characterizing
      negative effects development: higher activity of DNA oxidation products formation
      (according to increased urinary level of 8-OHdG), higher prevalence and
      variability of chromosomal polymorphism characterizing genetic instability of
      somatic cells, disbalance of sexual hormones (according to increased serum
      prolactine and lower FSH). These processes can result in functional disorders of
      pelvic organs, with increased prevalence of hormone-dependent gynecologic
      diseases in the female workers and remote effects in the offspring.

PMID- 25854079
TI  - [Premorbid markers of cardiovascular diseases in mining industry workers].
AB  - Functional studies of cardiovascular system in mine cutting machine operators
      with 10 years of underground length of service under exposure to occupational
      hazards (air pollution with sylvinite dust, noise, general and local vibration,
      increased humidity, absent natural illumination, work hardiness and intensity),
      helped to establish premorbid markers of cardial diseases--labile arterial
      hypertension, disordered processes of myocardial excitability, conductivity and
      automatism, higher thickness of intima-media complex in extracranial branches of
      brachiocephalic arteries. To decrease cardiovascular morbidity in mine cutting
      machine operators, the authors recommend additional blood pressure monitoring and
      ultrasound study of intima-media complex of extracranial brachiocephalic arteries
      within periodic medical examinations.

PMID- 25854080
TI  - [Treatment of occupational neurosensory deafness and noises in internal ear].
AB  - Neurosensory deafness treatment can be effective only after removal of specific
      etiologic factor--exposure toindustrial noise, that necessitates change of work
      and occupation, i.e. occupational disablement. Search for effective, complex
      methods to treat and prevent neurosensory deafness in patients exposed to
      occupational noise remains topical problem in otorhinolaryngology and
      occupational therapy. The article presents a method of treatment and prevention
      of neurosensory deafness in patients exposed to occupational noise; demonstrates
      its efficiency. Combination of medical therapy and physical therapy improves
      function of conductive pathways of hearing analyser, enables adequate
      rehabilitation of hearing in workers--that was confirmed by audiologic and
      neurofunctional parameters. The method is inexpensive, can be operative in
      medical stations at enterprises.

PMID- 25854081
TI  - [Evaluating exposure of population to dust, with consideration of components and
      dispersion contents of industrial discharges from enterprise extracting and
      processing mineral raw materials (discussion)].
AB  - The article covers results of study concerning disperse content of solid
      components of discharges from main dust- generating technologic operations in
      extraction and processing of mineral raw materials (pouring ore to conveyor,
      drying with combustion gas in fluid-bed, pouring of end product, sorting ore on
      riddle, drying on vibration dry and cool device, etc). Findings are that
      fractions under 10 and 2.5 micrometers approach 50% in general structure of dust
      discharges. Maximal share of low-disperse dust enters ambient air from vibraion
      dry and cool devices, riddles and pouring places. Exceeded reference values for
      acute and chronic exposure are registered on TSP and PM10 at a sanitary
      protection zone border and in the nearest living area points--that can forecast
      intolerable risks for health of population exposed and necessitate instrumental
      confirmation of the detected jeopardy level.

PMID- 25854082
TI  - [International scientific activity of Occupational Medicine Research Institute in
      2014].
AB  - The article presents results of international scrientific cooperation of the
      Institute in 2014, including participation in international conferences, forums,
      congresses.

PMID- 25854083
TI  - Molecular evidence for genetic distinctions between Chlamydiaceae detected in
      Siamese crocodiles (Crocodylus siamensis) and known Chlamydiaceae species.
AB  - Chlamydiosis, caused by Chlamydiaceae, is a zoonotic disease found in humans and
      several species of animals, including reptiles and amphibians. Although
      chlamydiosis in saltwater crocodiles has been previously reported in South Africa
      and Papua New Guinea, the reported strains have not been identified or confirmed.
      Therefore, the main aim of this study was to sequence and characterize
      Chamydiaceae isolated from Siamese crocodiles. Results showed the 16S ribosomal
      (r) RNA and the 16S/23S rRNA gene of the crocodile isolates were closely related
      to the genus Chlamydophila with matched identity greater than 98%. The
      phylogenetic tree constructed from the 16S/23S rRNA gene showed the crocodile
      cluster diverges far from Cp. caviae with a 100% bootstrap value. The tree based
      on the ompA gene loci distinguished the crocodile strains into genotypes I, II,
      and III. The present study is the first report on Chlamydophila detected in
      Siamese crocodiles that is genetically distinct from the known species of
      Chlamydiaceae.

PMID- 25854084
TI  - Antioxidant status, metabolic profile and immune response of lambs supplemented
      with tannin rich Ficus infectoria leaf meal.
AB  - To study the effect of supplementation of tanniferous tree leaves Ficus
      infectoria on antioxidant status and immune response, twenty four lambs were
      randomly divided into four groups of six each in a completely randomized design
      and fed either a conventional supplement (CON) or experimental supplements (FILM
      I, FILM-II and FILM-III) containing 1.0, 1.5 and 2.0% condensed tannins (CT),
      respectively by replacement of wheat bran of supplement CON with Ficus infectoria
      leaf meal (FILM). Blood biochemical profile was monitored in all lambs at 0, 45,
      90, 135, 180 days of feeding. Although haemato-biochemical parameters remained
      similar, there was significant (p < 0.05) improvement in catalase activity, total
      thiol and protein thiol groups with reduction in lipid peroxidation (LPO) in
      lambs fed FILM diet irrespective of levels. However, intracellular status of
      reduced glutathione, and superoxide dismutase activity was improved (p < 0.05)
      only in FILM-II and FILM-III supplemented lambs. The cell-mediated immune
      response was significantly (p < 0.05) improved in all the lambs fed FILM
      supplemented diets. Improved antioxidant status and immunity in FILM supplemented
      lambs increased voluntary feed intake irrespective of level. However, the average
      daily gain for a period of 180 d showed a significant (p < 0.05) increase by the
      supplementation of FILM-II diet containing 1.5% CT. The present study reveals
      that the supplementation of Ficus infectoria leaf meal up to 21.2% in the
      concentrate mixture could improve the antioxidant status and immunity in lambs.
      However, as feed efficiency was reduced at higher levels due to presence of CT,
      15.9% supplementation containing 1.5% condensed tannins in concentrate mixture is
      suggested to improve the health and production performance of lambs.

PMID- 25854085
TI  - Morphological characteristics observed during early follicular development in
      perinatal MRL/MpJ mice.
AB  - In perinatal mice, the ovary undergoes drastic morphological changes, as clusters
      of oocytes called nests break into smaller cysts and subsequently form individual
      follicles. We studied perinatal oocyte development in MRL/MpJ mice, and compared
      it to that observed in C57BL/6 mice between embryonic day 18.5 and postnatal day
      4. Throughout the observation period, compared to C57BL/6 mice, MRL/MpJ mice
      displayed significantly fewer oocytes in their ovaries. Morphologically, there
      were no clear differences between the strains at embryonic day 18.5. However, the
      beginning of folliculogenesis, as evidenced by the expression of NOBOX oogenesis
      homeobox (Nobox) transcript and protein, was more enhanced in MRL/MpJ mice than
      in C57BL/6 mice at embryonic day 18.5 and postnatal day 0. In addition, developed
      follicles were more frequently observed in MRL/MpJ mice than in C57BL/6 mice
      between postnatal days 0 and 4. In conclusion, the oocyte development during nest
      breakdown and folliculogenesis was accelerated in MRL/MpJ mice when compared to
      that observed in C57BL/6 mice.

PMID- 25854086
TI  - Quadricuspid aortic valves in Syrian hamsters and their formation according to
      current knowledge on valvulogenesis.
AB  - Occurrence of quadricuspid aortic valves has been reported in humans, in nine
      dogs and in a greater white-toothed shrew. Moreover, two cases of developing
      aortic valves with four anticipated leaflets have been described in Syrian
      hamster embryos. Currently, however, no case of quadricuspid aortic valve in
      adult hamsters has been recorded. The aim here is to present four adults of this
      rodent species, two of them with unequivocally quadricuspid aortic valves and the
      other two with quadricuspid-like aortic valves. The four anomalous aortic valves
      were detected among 4,190 Syrian hamsters examined in our laboratory,
      representing an incidence of 0.09%. None of the affected hamsters showed apparent
      signs of disease. The present findings are considered on the light of current
      empirical knowledge about the morphogenesis of quadricuspid and bicuspid aortic
      and pulmonary valves. Quadricuspid aortic valves result from the partition of one
      of the normal mesenchymal cushions which normally give rise to normal (tricuspid)
      valves, while quadricuspid-like valves might be the product of a combined
      mechanism of fusion and partition of the cushions at the onset of the
      valvulogenesis. The presence of aortic valves with four leaflets in ancient
      mammalian lineages such as insectivors and rodents suggest that quadricuspid
      aortic valves, although showing almost certainly a low incidence, may be
      widespread among the different groups of mammals, including domestic animals.

PMID- 25854087
TI  - Genetic diagnosis of band 3 deficiency using a quenching probe (QProbe)-PCR assay
      in bovine embryos.
AB  - The present study was conducted to develop a simple and rapid procedure to
      determine the genotype of band 3 deficiency in bovine embryos by a novel real
      time PCR method using a fluorescent quenching-based probe (QProbe-PCR). QProbe
      PCR successfully distinguished wild type and R664X mutant alleles by melting
      curve analysis. Minimal amounts of DNA template were required for the detection
      of wild type/wild type alleles, mutant/mutant alleles, and wild type/mutant
      alleles; their amounts were 10 pg, 25 pg, and 50 pg, respectively. When 10
      blastomeres were used as a DNA sample, accuracies of genotyping by QProbe-PCR
      were 100% and 89% in embryos homozygous for the wild type allele and heterozygous
      for the wild type and mutant alleles, respectively. QProbe-PCR takes
      approximately 2 h for genotyping and requires lesser time than the conventional
      method using PCR-RFLP, which requires digestion with a restriction enzyme and
      electrophoresis. Our data showed that QProbe-PCR is a useful method for rapid
      analysis of the genetic deficiency in preimplantation embryos. Reduction in the
      time required for genotyping enabled the transfer of genetically selected embryos
      to recipient cows on the day of embryo collection. These results suggest that
      determination of the genotype for the genetic deficiency in embryos is useful to
      select animals free from the genetic disease, and it also makes it possible to
      produce an animal model homozygous for the mutation.

PMID- 25854088
TI  - Putting women and the girl child at the Centre of Africa's Development.

PMID- 25854089
TI  - Reducing barriers to the use of the intrauterine contraceptive device as a long
      acting reversible contraceptive.
AB  - The intrauterine device (IUD) is the oldest long acting reversible contraceptive
      (LARC) method. There remain widespread barriers to its general acceptance,
      although some have been overcome, others remain. These stem from a lack of
      understanding of uterine anatomy and physiology. Uterine measuring techniques did
      not become popular, probably because of the extra effort required prior to IUD
      insertion. Unfortunately the information they provided regarding IUD design was
      also not heeded. In some countries varying sizes of other IUDs (second
      generation) are now available. The third generation hormonal carrying IUDs have
      also reduced barriers by lowering side effects and producing added health
      benefits. Fourth generation IUDs will provide added health benefits in addition
      to contraception and should further reduce barriers to IUD use. Most remaining
      IUD barriers are due to provider perceptions. Most are based on psychological,
      moral and religious prejudices. These should not be allowed to interfere with the
      provision of LARC methods of contraception. There are also acceptor barriers
      which can be modified by providing education about the method. The use of the IUD
      as a LARC method is increasing in many developed and developing countries. New
      technology should help propel the IUD into a more mainstream contraceptive.

PMID- 25854090
TI  - Perceived risk and condom use among adolescents in sub-Saharan Africa: a latent
      class analysis.
AB  - While studies have examined factors associated with condom use behaviors, few
      have assessed risk perception and condom use among SSA adolescents. This work
      sought to fill this gap. Data for this study are derived from the National Survey
      of Adolescents (2004-2005), a survey of 12-19 year olds in Burkina Faso, Ghana,
      Malawi, and Uganda. Latent class analysis was conducted. Two risk profiles
      emerged in the data. Percent of adolescents in the high perceived risk sub-groups
      ranged from 49.6% - 90.8% and moderate risk from 29.1-83.8%. Those in the high
      perceived risk class were 2.26 to 5.10 times more likely to report condom use.
      The findings provide additional information about the factors that influence
      condom use among adolescents in these four countries. Because an individual's
      development is influenced by his/her settings and systems, expanded views of
      behavior must be included in prevention efforts.

PMID- 25854091
TI  - Acceptability of the female condom by sub-Saharan African women: a literature
      review.
AB  - Sub-Saharan African women are affected disproportionately highly by AIDS, while
      experiencing lack of choice for devices which protect them against sexual
      transmitted diseases, including HIV. One should expect that global policy makers
      react positive to the female condom, a contraceptive device which offers dual
      protection. However, those policy makers often argue that the female condom is
      not acceptable to its users. Our objective is to find out whether this general
      statement is based on existing empirical data. Through a literature review we
      analysed empirical studies done between 2003 and 2013 and compared the extent to
      which female condoms were acceptable among women in sub-Saharan Africa. We found
      that acceptability was defined in different ways, along the line of two types of
      studies: intervention and non-intervention studies. The intervention studies
      defined acceptability as women who agreed to use the female condom several times.
      The non-intervention studies which were not linked to specific interventions,
      operationalized acceptability in terms of women who liked the female condom, not
      necessarily based on practical experience or use. Intervention studies led to a
      high proportion of women using the technology, rating the experiences as
      satisfactory, although recommending technical improvements. In contrast, non
      intervention studies showed low use due to non-acceptability mixed with reasons
      of unfamiliarity, unavailability or unaffordability. We concluded that women in
      sub-Saharan Africa accepted the use of the female condom when potential users
      were given access to the device, and exposed to interventions which supported the
      use of a female condom.

PMID- 25854092
TI  - Effect of school-based human papillomavirus (hpv) vaccination on adolescent
      girls' knowledge and acceptability of the HPV vaccine in Ibanda District in
      Uganda.
AB  - From 2008 to 2011, schoolgirls were vaccinated against HPV in two districts in
      Uganda following sensitization. This study assessed girls' knowledge of cervical
      cancer and HPV vaccine, and their acceptance of future vaccination of friends and
      hypothetical daughters. The cross-sectional, mixed methods comparative study was
      conducted in two districts. Univariate, bivariate, logistic regression and
      thematic analyses were done. HPV vaccination was positively associated with
      knowledge (Crude OR: 5.31, CI: 3.19-8.86; p = 0.000); but knowledge (Adjusted OR:
      1.13, CI: 0.56-2.28; p = 0.73) and HPV vaccination (Adjusted OR: 0.92, CI: 0.16
      5.36; p = 0.93) did not predict vaccine acceptability. Seemingly important
      motivations for vaccine acceptance were: its role in cancer prevention and
      advancement of reproductive health, minimal side effects, and positive peer role
      models. Major deterrents to vaccine acceptance were: rumours and misconceptions
      about possible side effects, perceived inadequate information about vaccine, and
      fear of side effects.

PMID- 25854093
TI  - Determinants of fertility intention among women living with hiv in western
      Ethiopia: implications for service delivery.
AB  - Despite increased emphasis on antiretroviral therapy for HIV infected
      individuals, issues of fertility and childbearing have received relatively little
      attention in Ethiopia. This study was conducted to assess socio-demographic,
      reproductive and HIV related characteristics of fertility intention among women
      living with HIV in Western Ethiopia. Cross sectional study was conducted from May
      I to May 26, 2012 using structured questionnaire on a sample of 456 women living
      with HIV who are on follow up care in anti-retroviral therapy clinics. Bivariate
      and multivariable logistic regression models were fitted to identify significant
      predictors of fertility desire at 95 CL. Out of 456 respondents 42.1% expressed
      intention to have children in the future. Educational attainment [AOR (95% CI) =
      0.041(0.008-0.220)], partner fertility desire [AOR (95% CI) = 0.012 (0.004
      0.034)], number of live children [AOR (95% CI) = 0.344 (0.125-0.950)] and partner
      sero-status [AOR (95% CI) = 6.578 (4.072-10.881)] were significantly associated
      with fertility intention. A large proportion of HIV-positive women in the study
      desired more children in future. Interventions to address this problem include
      integrated access to contraception methods, and counselling on reproductive
      health decision-making.

PMID- 25854094
TI  - Reproductive coercion and intimate partner violence among rural women in Cote
      d'Ivoire: a cross-sectional study.
AB  - A growing body of U.S.-based research demonstrates that reproductive coercion is
      an important consideration regarding the negative health impacts of intimate
      partner violence (IPV). However, less work on IPV and reproductive coercion has
      been done in West African settings. Cross-sectional data of 981 women who
      participated in the baseline survey of a randomized-controlled trial in rural,
      Cote d'Ivoire in October 2010 were analyzed for specific reports of reproductive
      coercion. Half (49.8%) of all women reported lifetime physical or sexual IPV, and
      nearly 1 in 5 (18.6%) reported experiencing reproductive coercion. In the final
      adjusted analyses, lifetime IPV was associated with a 3.7 increase in odds of
      reporting reproductive coercion (95% CI: 2.4-5.8) compared to women who did not
      report such victimization. Study findings underscore the importance of reducing
      IPV in order to improve reproductive health among women in rural Cote d'Ivoire.

PMID- 25854095
TI  - Audit of cervical cancer screening and colposcopy attendance in rural South
      Africa.
AB  - Women in developing countries generally lack access to cervical cancer preventive
      services. An audit was performed in rural South Africa to test the hypothesis
      that women do not follow (pre-)cancerous cervical disease treatment sufficiently,
      to understand the possible reasons for this non-attendance behavior, and to
      evaluate other published diagnostic and treatment initiatives. Based on Pap smear
      and colposcopy attendance data, including age, HIV status, month of attendance,
      and cervical intraepithelial neoplasia (CIN) staging, relatively few patients
      (54% of 928 patients) visited a colposcopy clinic following an abnormal Pap
      smear. Although these co-factors do not explain this high non-attendance rate,
      HIV status was an important co-factor; percentage-wise, HIV positivity correlated
      with a higher attendance rate. Screening methods that use mobile teams to
      successfully deliver cost-effective on-the-spot treatment warrant further
      attention.

PMID- 25854096
TI  - Sexual violence among female undergraduates in a tertiary institution in Port
      Harcourt: prevalence, pattern, determinants and health consequences.
AB  - The prevalence, pattern, determinants and health consequences of sexual violence
      on female undergraduates attending the University of Port Harcourt in the Niger
      Delta region of Nigeria was investigated. The study was a cross-sectional study
      involving 413 female students, and consisted of self-administered questionnaires.
      Data were analysed using Epi Info v6.04d and presented as frequency tables.
      Associations were tested using Chi square and Odds Ratio, p < 0.05, at 95% CI.
      Mean age was 22.1 +/- 2.8. One hundred and ninety three (46.7%) had suffered from
      one form of sexual violence or the another. Fondling/grabbing of sensitive body
      parts was the commonest 65(33.7%) form of sexual violence. Intimate partners
      topped the list of perpetrators. Year of study (p=0.006, OR 0.57, CI=0.39-0.85),
      prior victimization (p=0.049, OR=1.52, CI = 1.00-2.30) and consensual sexual
      activity (p=0.001, OR=1.92, CI = 1.29-2.84) were associated with sexual violence.
      Depression and guilt were the major health consequences reported. Sexual violence
      is high at the University of Port Harcourt, which warrants targeted preventive
      action.

PMID- 25854097
TI  - Assessment of maternal satisfaction with facility-based childbirth care in the
      rural region of Tambacouda, Senegal.
AB  - In Senegal, only 60% of mothers in rural areas deliver in health facilities.
      Mothers' satisfaction with their facility-based childbirth experience is one of
      the factors in their choosing to deliver in such facilities in subsequent
      pregnancies. The objective of this study was to assess whether compliance with
      childbirth care based on the mothers' perception of facility-based childbirth
      care contributes to the degree of maternal satisfaction. We conducted a secondary
      analysis of cross-sectional survey data collected from 259 mothers who had normal
      deliveries at facilities in rural areas of Senegal in 2011. The association
      between overall maternal satisfaction with childbirth care and 23 standard care
      survey items was assessed. The results showed that the degree of compliance with
      standard care and eight of 23 survey items were associated with maternal
      satisfaction. We conclude that to improve maternal satisfaction, facilities need
      to guarantee compliance with standard care.

PMID- 25854098
TI  - Do knowledge and cultural perceptions of modern female contraceptives predict
      male involvement in Ayete, Nigeria?
AB  - Male involvement is crucial to female contraceptive use. This study examined how
      male knowledge and cultural perceptions of modern female contraceptives influence
      involvement in contraceptive use. A cross-sectional survey of 389 men from Ayete,
      Nigeria was used to regress a continuous male involvement score on demographic
      variables, knowledge of at least one method of modern female contraception and a
      scored male perception variable using Ordinary Least Squares regression.
      Controlling for perception, the knowledge of at least one method of modern female
      contraception was not significantly associated with a change in male involvement
      (p=0.264). Increasing positive perception was associated with higher male
      involvement scores (p=0.001). Higher educated males, those with a current desire
      to have children and males whose partners were currently using a method had
      greater male involvement scores (p<0.05). Policy and intervention efforts should
      be focused on changing cultural perceptions, in addition to providing in-depth
      knowledge of contraceptive methods.

PMID- 25854099
TI  - Maternal and fetal prognosis in abruptio placentae at Korle-Bu Teaching Hospital,
      Ghana.
AB  - The study provided baseline data of abruptio placentae in Korle-Bu Teaching
      Hospital (KBTH), Ghana, and gave recommendations to minimize poor outcomes. A
      prospective cross sectional study was conducted at the Maternity Department of
      the KBTH between February 2008 and January 2010. Two hundred women with diagnosis
      of placental abruption were studied using a pretested standardized structured
      questionnaire. Statistical Package for Social Sciences (SPSS) version 17 was used
      to analyse the data. Fifteen thousand five hundred and ten (15,510) deliveries
      were recorded during the study period out of which 1.4% abruptio placentae cases
      were confirmed. The perinatal and maternal mortality rates were 65% and 2%
      respectively. The key risk factors identified were low socio-economic status,
      grandmultiparity and hypertensive disorders in pregnancy. Intrauterine foetal
      death, (IUFD) and maternal shock were significantly associated with coagulopathy
      (p=0.001 and 0.004 respectively). Early diagnoses of placental abruption will
      significantly improve foetal and maternal survival.

PMID- 25854100
TI  - Case report: A healthy live birth following icsi with retrograde ejaculated
      sperm.
AB  - Retrograde ejaculation, sometimes called dry orgasm, refers to the medical
      condition when semen enters the urinary bladder (retrograde) instead of emerging
      through the penis after orgasm (antegrade). In some instances, a very minute
      quantity of antegrade semen appears in the ejaculate and may or may not be devoid
      of spermatozoa. Complete retrograde ejaculation causes male infertility.
      Intracytoplasmic sperm injection (ICSI) has been employed to achieve
      fertilization in some cases of male subfertility, e.g., severe
      oligoasthenoteratozoospermia. Assisted reproductive techniques to aid conception
      in cases of retrograde ejaculation have been described extensively elsewhere but
      there is paucity of knowledge on the occurrence and treatment in Africa. This
      case report describes the identification and successful treatment of a couple
      where the male partner suffered from retrograde ejaculation.

PMID- 25854102
TI  - The physical state of potassium in frog skeletal muscle studied by ion-sensitive
      microelectrodes and by electron microscopy: interpretation of seemingly
      incompatible results.
AB  - According to the commonly accepted membrane pump theory most of cellular K+ ions
      are freely dissolved in free cellular water; the alternative association
      induction hypothesis postulates that the bulk of cellular K+ is adsorbed (weakly
      bound) to cellular proteins that are maintained in a specific labile state in the
      cytoplasm of a living cell. K+ activities measured with ion-sensitive
      microelectrodes in the cytoplasm of frog skeletal muscle seem to confirm the
      claim that most of cellular K+ ions are free in cellular water. On the other
      hand, it is evident from electron microscopic ion binding studies that in frog
      skeletal muscle most of cellular K+ ions are adsorbed to cellular proteins. The
      conflicting results can be explained with the assumption that a damage of the
      cytoplasm caused by the impaling microelectrode leads to a liberation of adsorbed
      ions. Using the light microscope tests the possibility that microelectrodes
      damage the muscle cytoplasm. It is found that microelectrodes produce visible
      traumas that increase with time. Electron microscopic ion binding studies with
      damaged muscle support the view that monovalent cations are liberated in the
      disturbed area of a muscle fiber. It is concluded that a K(+)-sensitive
      microelectrode is not suited to determine the concentration of free K+ ions in
      intact frog skeletal muscle.

PMID- 25854101
TI  - Can we see living structure in a cell?
AB  - Colloid chemistry (kappaomicronlambdalambdaalpha: glue, or gelatin) was
      introduced in 1861 after the discovery of protoplasm, which exhibits gelatin-like
      properties. Some 80 years later, colloid chemistry (and with it, the concept of
      protoplasm) was largely abandoned. The membrane (pump) theory, according to which
      cell water and cell solute like K+ are free as in a dilute KC1 solution, became
      dominant. Later studies revealed that rejecting the protoplasmic approach to cell
      physiology was not justified. Evidence against the membrane (pump) theory, on the
      other hand, has stood the test of time. In a new theory of the living cell called
      the association-induction (AI) hypothesis, the three major components of the
      living cell (water, proteins and K+) are closely associated; together they exist
      in a high- (negative)-energy-low entropy state called the living state. The bulk
      of cell water is adsorbed as polarized multilayers on some fully extended protein
      chains, and K+ is adsorbed singly on beta- and gamma-carboxyl groups carried on
      aspartic and glutamic residues of cell proteins. Extensive evidence in support of
      the AI hypothesis is reviewed. From an extension of the basic concepts of the AI
      hypothesis and the new knowledge on primary structure of the proteins, one begins
      to understand at long last what distinguishes gelatin from other proteins; in
      this new light, new definitions of protoplasm and of colloid chemistry have been
      introduced. With the return of the concept of protoplasm, living structure takes
      on renewed significance, linking cell anatomy to cell physiology. Finally,
      evidence is presented showing that electron microscopists have come close to
      seeing cell structure in its living state.

PMID- 25854103
TI  - [On the notes of the Xinkan Huangdimingtangjiujing (see text for symbol) in the
      possession of the National Diet Library].
AB  - This paper analyzes the notes of Xinkan huangdimingtangjiujing which are in the
      possession of the National Diet Library, particularly referring to those notes
      which include "master said", or "master's theory". Some of those are found in the
      answers from Manase Dosan (see text for symbol) to Hata Soha (see text for
      symbol) collected in the Kotei meido kyukyo hushin shosho (see text for symbol)
      which is the record of the question and answer letters between Manase Dosan and
      Hata Soha. This research indicates that this volume has a close relation to the
      acupuncture research of Dosan's or Soha's school. And it indicates that the
      "master" in the Notes of Xinkan huangdimingtangjiujing refers to Dosan.
      Acupuncture research has been flourishing since the Edo era and has compiled a
      lot of volumes on acupuncture. This volume contains some pioneering pieces of
      this research done in the Azuchi Momoyama era by Dosan and Soha, and is a
      precious material, showing that some of the state of affairs of the research done
      in that age still remains today.

PMID- 25854104
TI  - [The movement to establish a Christian medical school proposed by medical
      missionary "John C. Berry"].
AB  - John C. Berry (1847-1936) came to Japan in 1872, worked as a medical missionary
      for the American Board of Commissioners for Foreign Missions (ABCFM . He
      attempted to influence Japanese medical education toward a more Christian
      influenced approach. In early Meiji, the Japanese government adopted the German
      language and principles for its national medical program. This promoted a
      tendency towards the adoption of German concepts in Japanese medical education.
      The director of of Doshisha, Niijima, was concerned about such a tendency, which
      he considered rather science-oriented or skeptical and atheistic, according to
      his writings. The tradition of corruption among Japanese doctors also deeply
      disappointed him. Niijima sought the type of medical institution in which the
      students would learn Western medicine based on a moral base of Christianity,
      presumably in Kyoto, to take advantage of the foundation of Doshisha, which had
      already been built. Missionaries in Japan, especially Berry, supported Niijima's
      intentions. During his visit to the U.S. he promoted a mission statement in
      support of Niijima's idea in order to raise funds among Christian communities.
      This project produced a resolution among the Christian community in Philadelphia
      to establish an interdenominational foundation for establishing such a medical
      institution and it encouraged other cities to follow. However, the American Board
      of Missionaries in Japan disagreed with the idea of its being
      interdenominational, and then, along with other struggles such as the lack of
      funding in light of the economic slowdown, and the widespread social rejection of
      Christianity in Japan, the project fell apart and was suspended.

PMID- 25854105
TI  - [Tokijirou Kaji, the pioneer of socializing medical practice in Japan].

PMID- 25854106
TI  - [Council designated lectures 'progress in study of novel mechanisms for ocular
      diseases].

PMID- 25854107
TI  - [The vitreous and the macula].
AB  - The macula is a site where various vitreoretinal disorders occur. In 1983 we
      started to observe the retinal surface of postmortem eyes with a scanning
      electron microscope (SEM). We investigated the anatomy of the vitreous in
      postmortem eyes by slit lamp biomicroscopy. The novel anatomy of the premacular
      vitreous led us to conduct a clinical study of vitreomacular interface diseases.
      In 1997, time domain optical coherence tomography(OCT) became available which
      facilitated visualization of the vitreoretinal interface. Swept source OCT which
      was introduced in 2012 can depict liquefied lacunae in the vitreous. It enabled
      us to elucidate the mechanism of vitreoretinal diseases. I. SEM revealed the
      remnants of vitreous cortex at fovea with high incidence (44%), which suggests
      strong vitreoretinal attachment at the fovea and vitreous cortex origin of the
      epiretinal membrane. II. We studied the anatomy of the vitreous in postmortem
      eyes. The vitreous of bisected eye balls was stained by fluorescein and immersed
      in water and observed by slit-lamp biomicroscopy. We discovered a "posterior
      precortical vitreous pocket (PPVP)" in adult eyes without posterior vitreous
      detachment (PVD). III. We performed clinical study in various vitreoretinal
      diseases based on the novel vitreous anatomy and explained their mechanism. 1. In
      diabetic retinopathy, ring shaped fibrovascular tissue surrounding the macula is
      formed along the outer margin of the PPVP. Although PVD progresses outside the
      PPVP, its posterior wall remains attached to the retina, which causes macular
      traction or cystoid macular edema. 2. In eyes with idiopathic epimacular membrane
      (IEM), detached vitreous cortex had an oval defect corresponding to the IEM.
      Posterior wall of the PPVP that is premacular vitreous cortex appeared to be the
      framework of IEM. 3. During vitrectomy for macular hole, premacular round defect
      appears when PVD is created. The residual cortex on the macula is fibrous
      membrane with elasticity. The tangential contraction of premacular cortex may
      generate anterior traction to the fovea, which leads to macular hole. IV. Using
      time domain OCT, we demonstrated the evolution of macular hole, myopic
      foveoschisis and lamellar macular hole. After 2007, we investigated age related
      changes of vitreoretinal interface by spectral domain OCT V. We demonstrated
      whole structure of the PPVP using swept source OCT. PPVP is a boat shaped
      premacular liquefied space which has a connecting channel to Cloquet's canal.
      PPVP develops during childhood. Visualization of vitreous structure proved that
      our previous assumptions are reasonable. Although the physiological function of
      the PPVP is unclear, we speculate that the aqueous flows into the PPVP though
      Cloquet's canal and the connecting channel.

PMID- 25854108
TI  - [Battle with herpes for 37 years].
AB  - Herpes simplex virus type 1(HSV-1) remains latent in the human trigeminal
      ganglion after primarily infecting the cornea and conjunctiva. Mental stress,
      heat stimulation, ultraviolet ray and immunosuppression are among the
      reactivating factors of HSV-1, which can lead to epithelial herpetic keratitis,
      stromal herpetic keratitis, and other complications. I have been working with HSV
      1 for a long time, concentrating especially on its latency and reactivation. I
      would like to introduce some of the recent research results. 1. Herpetic
      keratitis cases at the Department of Ophthalmology, Kinki University. There were
      129 eyes of 128 patients who visited the Cornea Service in our university
      hospitals at Osayasayama, Sakai and Nara over 13 years and were diagnosed with
      herpetic keratitis and followed up for at least one year. They were investigated
      as to the type of herpetic keratitis at the initial visit and its recurrence.
      Initial types of herpetic keratitis and number of eyes of each type were:
      Epithelial type, 65 eyes (50%); Stromal type, 30 eyes (23%); Combined epithelial
      and stromal types, 18 eyes (14%). Recurrence was seen in 47% of the total 129
      eyes. Recurrent cases of the epithelial type were mostly epithelial type.
      Frequently recurrent cases of the stromal type presented with repeated
      epithelial, stromal, and combined types. 2. Effects of antiherpetics on mouse
      epithelial herpetic keratitis. Acyclovir (ACV) eye ointment is usually prescribed
      for several weeks to treat human epithelial herpetic keratitis. Our question is:
      Is this long administration really necessary? To find the answer to this
      question, we investigated time-dependent effects of antiherpetics on mouse
      epithelial herpetic keratitis. Mouse corneas were infected with HSV-1 and either
      ACV eye ointment, oral valaciclovir (VACV) or oral famciclovir (FCV) was
      administered. No virus was detected in the tear fluid examined by viral culture 4
      days after start of ACV eye ointment or oral VACV and 6 days after start of oral
      FCV. Real-time PCR revealed significant decrease of HSV DNA copy number in the
      eyeball or trigeminal ganglion compared to saline instillation 4 and 6 days after
      start. These results suggest that antivirals for 5 days could sufficiently
      decrease the HSV amount in the ocular surface and eyeball. 3. Corneal latency. In
      order to prove latency of HSV in the human cornea, virological and molecular
      biological techniques were used to ensure the following 3 prerequisites. 1)
      Positive HSV DNA in the human cornea. 2) Negative homogenate, positive explant.
      3) Only latency-associated transcript (LAT) detected and transcriptional products
      of other virus genes (alpha, beta, gamma) not detected in the cornea. As a
      result, all the 3 prerequisites have been satisfied in the 3 corneas that had a
      past history of herpetic keratitis. This result suggests that HSV could remain
      latent in the human cornea. 4. Detection of HSV-1, HHV-6, and HHV-7 DNA in the
      anterior segment and aqueous humor using multiplex real-time PCR. Multiplex real
      time PCR was applied for the first time ever in opththalmology to human herpes
      virus 6 (HHV-6) and 7(HHV-7). Samples taken from tear fluid before and 3 days
      after phacoemulsification and aspiration (PEA) or penetrating keratoplasty (PKP),
      and aqueous humor aspirated during PEA were used. The results of multiplex real
      time PCR showed HSV-1, HHV-6 and HHV-7 DNA present in tear fluid both before and
      after PEA or PKP. 5. Gene expression when reactivation is suppressed. Nuclear
      factor-kappaB (NF-kappaB) has recently been reported to be involved in
      reactivation of HSV-1. IkappaB kinase-beta (IKK2) inhibitors, which inhibit the
      activity of NF-kappaB, were used to examine gene expression during HSV
      reactivation in a mouse model. Significant decrease of HSV DNA copy number was
      observed at the trigeminal ganglion with real-time PCR in a group which was given
      IKK2 inhibitors intraperitoneally. Microarray method demonstrated 2-fold or more
      increased expression of 1812 probe. By Pathway analysis, eased immunosuppressive
      effects were observed in the group which was given IKK2 inhibitor
      intraperitoneally. 6. Immunoresponse involved in herpetic keratitis. Chemokine
      expression profiles in human corneal herpetic cases and mouse herpetic keratitis
      were analyzed. The results were similar to previously published reports: Cxcl9,
      Cxcl10, Ccl5, which are Th1 type chemokines, and Ccl20, a Th17 type chemokine,
      were observed to increase. On the other hand, Th2 type chemokine did not show an
      increase. Immunoresponse occurred mainly in the trigeminal ganglion. With these
      results, we suggest herpetic keratitis could be prevented by actively inducing
      Th17 type immunoresponse.

PMID- 25854109
TI  - [Aiming for zero blindness].
AB  - Glaucoma is the leading cause of acquired blindness in Japan. One reason that it
      often leads to blindness is that it can continue to worsen even after effective
      medical reduction of intraocular pressure (IOP), the only evidence-based
      treatment. The limitations of current treatments make it critical to identify IOP
      independent factors that can cause glaucoma and develop new drugs to target these
      factors. This is a challenging task, as the pathology of glaucoma is thought to
      be very complex, with different combinations of factors underlying its
      development and progression in different patients. Additionally, there is a
      deficiency in methods to efficiently perform clinical evaluations and reliably
      probe the state of the disease over relatively short periods. In addition, newly
      developed drugs need to be evaluated with clinical trials, for which human and
      financial resources are limited, before they can be widely used for treatment.
      Taking all these issues into consideration, it is evident that there are two
      urgent issues to consider: the development of methods to classify glaucoma in
      detail based on its pathology, and the improvement of clinical evaluation
      methods. In this review, we discuss some of our efforts to develop new
      neuroprotective agents for glaucoma, with a focus on the following three areas:
      1. Clinical research and development of methods to classify glaucoma in detail
      based on IOP-independent factors, and the exploration of possibilities for the
      improvement of clinical evaluation of glaucoma. 2. Pathology-based research and
      development of new drugs for glaucoma, focusing on comprehensive gene expression
      analysis and the development of molecule-targeting drugs, using murine optic
      nerve crush as a disease model. 3. Development of next generation in vivo imaging
      modalities and the establishment of infrastructure enabling "big-data" analysis.
      First, we discuss our clinical research and the development of methods to
      classify glaucoma in detail based on IOP-independent factors, as well as our
      investigation of ways to improve the clinical evaluation of the disease. Our
      research was prompted by the multifactorial nature of glaucoma. There is a high
      degree of variability in the pattern and speed of the progression of visual field
      defects in individual patients, presenting a major obstacle for successful
      clinical trials. To overcome this, we classified the eyes of glaucoma patients
      into 4 types, corresponding to the 4 patterns of glaucomatous optic nerve head
      morphology described: by Nicolela et al. and then tested the validity of this
      method by assessing the uniformity of clinical features in each group. We found
      that in normal tension glaucoma (NTG) eyes, each disc morphology group had a
      characteristic location in which the loss of circumpapillary retinal nerve fiber
      layer thickness (cpRNFLT; measured with optical coherence tomography: OCT) was
      most likely to occur. Furthermore, the incidence of reductions in visual acuity
      differed between the groups, as did the speed of visual field loss, the
      distribution of defective visual field test points, and the location of test
      points that were most susceptible to progressive damage, measured by Humphrey
      static perimetry. These results indicate that Nicolela's method of classifying
      eyes with glaucoma was able to overcome the difficulties caused by the diverse
      nature of the disease, at least to a certain extent. Building on these findings,
      we then set out to identify sectors of the visual field that correspond to the
      distribution of retinal nerve fibers, with the aim of detecting glaucoma
      progression with improved sensitivity. We first mapped the statistical
      correlation between visual field test points and cpRNFLT in each temporal clock
      hour sector (from 6 to 12 o'clock), using OCT data from NTG patients. The
      resulting series of maps allowed us to identify areas containing visual field
      test points that were prone to be affected together as a group. We also used a
      similar method to identify visual field sectors within a 10 x 10 grid displayed
      by an OCT map of the macula. By analyzing both the visual field and the macular
      map sectors, we anticipate that a more accurate and sensitive detection of
      glaucoma progression can become possible. We also used laser speckle flowgraphy
      (LSFG) to assess optic nerve blood flow. We found that compared to healthy eyes,
      eyes with early-stage NTG had decreased blood flow, and the peak of the blood
      flow wave form of each heartbeat was delayed. Finally, we used a method combining
      swept source OCT (SS-OCT) and newly developed analysis software to reconstruct
      the entire lamina cribrosa, a structure situated deep in the optic nerve head.
      This morphological analysis returned preliminary data suggesting that alterations
      in the morphology of the lamina cribrosa are already present in the early stages
      of glaucoma. This result indicates that axonal injury, mediated by morphological
      abnormalities of the lamina cribrosa, is involved in the pathogenesis of
      glaucoma. The next topic discussed is the pathology-based drug research and
      development, focusing on the use of comprehensive gene expression analysis and
      the development of molecule-targeting drugs in a murine model of optic nerve
      injury. Learning from clinical data on glaucoma and the lamina cribrosa, we
      carried out basic research to first determine what factors regulate axonal
      injury, and then develop drugs targeting these factors. Specifically, we
      performed a comprehensive gene expression analysis, using a next generation
      sequencer, and pathway analysis of retinal samples obtained from a murine model
      of axonal injury. This analysis revealed a characteristic upregulation of genes
      (such as Chop) that belongs to the endoplasmic reticulum stress pathway. An
      immunohistological analysis revealed that these changes in gene expression took
      place in the retinal ganglion cells, suggesting that endoplasmic reticulum stress
      molecules may be suitable therapeutic targets. Among these molecules, we chose
      CHOP as our primary target for drug development. Currently, we are in the process
      of screening a library of 1274 drugs, all of which are already used in human
      subjects, for CHOP inhibitors. The last topic of our discussion is future
      possibilities for glaucoma management. First, we discuss the development of next
      generation in vivo imaging modalities that allow detailed description of
      pathomechanisms of this multifactorial disease, glaucoma. The purpose of this
      research was to improve the efficacy of glaucoma diagnosis and to visualize its
      pathology at a cellular/molecular level and develop molecule-specific therapies.
      Currently available visual field tests are subjective, since they rely on a
      determination of the threshold of light perception, and are affected by poor
      reproducibility. The current dependence on visual field tests to ascertain the
      progression of glaucoma is thus a serious limitation on an important task of
      ophthalmologists. We, therefore, turned our focus to the establishment of an in
      vivo imaging method to detect dying retinal ganglion cells, which would highlight
      the pathologic state of glaucoma with high sensitivity. To this end, we used
      confocal scanning ophthalmoscopy to assess the usefulness of SYTOX Orange as a
      cell death probe. Our results showed that this probe could reveal dying retinal
      ganglion cells clearly, quickly and with high sensitivity. We, therefore, believe
      that the clinical application of probes that can sensitively detect dying retinal
      ganglion cells is a highly promising approach. This also applies to the use of
      molecular tools that can provide information on the molecular pathology of
      glaucoma. Finally, we would like to introduce our national collaborative work on
      the analysis of "big-data". The project aims to collect as wide a range of data
      as possible at an unprecedented scale. The data to be registered ranges from
      basic glaucoma data, such as IOP and visual field test results, to data from the
      most sophisticated comprehensive expression analyses or imaging data. This is an
      important area of research, since it promises to enable the exploration of
      targets for drug discovery and the identification of new biomarkers to
      efficiently detect glaucoma progression by applying new analysis strategies to
      the complex mass data. The project not only depends on the collaborative efforts
      of various types of clinical settings including private practices, medical
      centers and university hospitals, but also contributions of the pharmaceutical
      and the medical device industries. Thus, uniting a wide range of Japanese
      interests and resources is the key for success. In summary, in order to aim for
      ZERO BLINDNESS, a drastic improvement in the quality of our patient care, drug
      development research for unmet medical demands, and a strategic collaboration of
      various professionals in the ophthalmic industry are essential. With the deep
      appreciation we fell towards the selfless support extended during the earthquake
      disaster, we wish to translate our "gratitude" into "power" from Tohoku. In doing
      so, we as academicians are determined to keep on contributing to the society by
      making progress in the medicine.

PMID- 25854110
TI  - [Age-related macular degeneration: paradigm shift from recent findings].
AB  - This review describes recent advances in age-related macular degeneration (AMD),
      based mainly on our own research findings. First, we investigated the effect of
      choroidal abnormality and found that choroidal hyperpermeability was observed
      more often in eyes with polypoidal choroidal vasculopathy (PCV) than in eyes with
      typical AMD; however, even in eyes with typical AMD, substantial proportion of
      eyes showed hyperpermeability. Exudative AMD eyes with choroidal
      hyperpermeability showed thickened choroid more widely than previously
      demonstrated, and there were more frequent abnormalities with fundus
      autofluorescence examination. Thus, rather than classifying exudative AMD into
      PCV and typical AMD, AMD classification by choroidal hyperpermeability may be
      useful in illustrating the difference of certain clinical characteristics.
      Second, we investigated the importance of vitreomacular adhesion in the treatment
      outcome of exudative AMD. The currently prevailing hypothesis is that premacular
      VEGF concentration is lower in eyes with posterior vitreous detachment (PVD) than
      in eyes without PVD, thus leading to good treatment outcomes; however, in the
      current study, we showed that not only VEGF but also anti-angiogenic factor,
      interferon-inducible protein 10 (IP-10), is affected according to PVD. These
      results suggest that the effect of PVD on the intraocular environment is more
      complicated than previously thought, and may have diverse functions. Last, we
      explained the mechanism of AMD progression based mainly on our basic research.
      Our research showed that age-related decline of autophagic activity may, at least
      partly, contribute to the precursor lesion of AMD.

PMID- 25854111
TI  - [Novel mechanism for retinal vascular diseases].
AB  - I. A new therapeutic target for diabetic retinopathy. Recent reports state that
      succinate may be an independent retinal angiogenic factor. We evaluated
      concentrations in vitreous from proliferative diabetic retinopathy (PDR), and
      found that succinate increased significantly in PDR. Interestingly, levels of
      succinate from bevacizumab-pre-injected PDR were normal, suggesting that vascular
      endothelial growth factor (VEGF) had a positive feedback mechanism for succinate
      since succinate was previously reported to induce VEGF. II. A new understanding
      of central retinal vein occlusion (CRVO). We evaluated retinal blood flow
      velocity with laser speckle flowgraphy (LSFG) made in Japan, and found that cases
      in which both macular edema and retinal blood flow velocity improved after anti
      VEGF therapy had better prognosis. In ischemic CRVO at final visit, mean retinal
      blood velocity was less than 50% of fellow eyes after 1st anti-VEGF therapy,
      suggesting that those cases might have poor prognosis. LSFG is useful for
      evaluation and decision in CRVO treatment. III. From exploration for mechanism in
      retinal vascular diseases to re-vascularization therapy. The standard treatment
      for retinal non-perfusion area is scatter laser photocoagulation, which is both
      invasive of the peripheral retina and may prove destructive. Re-vascularization
      is an ideal strategy for treatment of retinal non-perfusion area. To develop a
      new methods for re-vascularization in retinal non-perfusion area, we have
      designed experiments using a retina without vasculature differentiated from
      induced pluripotent stem(iPS) cells.

PMID- 25854112
TI  - [Neurochemical mechanisms of a need, motivation and goal-directed behavior].
AB  - In this review is analyzed four kinds of needs, which include both humans and
      animals. These are: 1--the need to eat 2--need to drink 3--sexual need and, 4-
      the need to enhance or prolong the positive emotional state, and conversely, the
      need to dispose or avoid pain and unpleasant effects or negative emotional state.
      The centers of the first three needs are localized in the hypothalamus. The
      fourth need induced by integrative processes and determined the key role of the
      mesolimbic dopamine (DA) system of brain. Leptin and ghrelin, a hormone of
      satiety and hunger form of food motivation in neurons food center of the
      hypothalamus interacting with DA signal. Vasopressin, antidiuretic hormone, form
      drinking motivation in the neurons of hypothalamus drinking center interacting
      with DA signal. Vasopressin, oxytocin and steroid hormones form a sexual
      motivation in the neurons of the sexual center of the hypothalamus interacting
      with DA signal. Terminals of the mesolimbic DAergic system innervate hypothalamic
      neurons, amygdala, habenula and nucleus accumbens. The part of the neurons of
      amygdala and habenula respond to positive stimuli, and the other part to the
      negative stimuli. Integrative structure of mesolimbic DAergic system is the
      nucleus accumbens. GABAergic terminals of this nucleus terminate on exterior and
      interior nucleus of the ventral pallidum. Describes and discusses the emotional
      and motivational network and their interaction on the global DAergic signal.

PMID- 25854113
TI  - [Food-derived opioid peptides and their neurological impact].
AB  - In this review the up-to-date literature data about exorphins are analysed.
      Exorphins are short opioid-like food-derived peptides. Different reports about
      their physiological impact in animals and humans are reviewed with focus on
      neurotropic effects. Clinical data (case reports and clinical trials' results),
      on the one hand, and the results of experiments with animals of different taxons,
      on the other hand, are summarized. The influence of exorphins on infants'
      development is emphasized.

PMID- 25854114
TI  - [Epigenetic mechanisms in post-stress states].
AB  - There is a continued interest in the research of epigenetic mechanisms of genes
      regulation in the brain, associated with the stress-induced adaptive and
      pathological consequences during the formation of post-stress states, in
      particular post-traumatic stress disorder (PTSD). Brief overview of epigenetic
      modifications was presented, while the process of DNA methylation was discussed
      comprehensively. Key stress-induced epigenetic changes in the human and animal
      brain in response to stress were summarized. Epigenetic modifications in certain
      genes (genes of stress responses, hormones and neurotransmitters genes, NGF gene)
      while post-stress states and PTSD formation were discussed in detail.

PMID- 25854115
TI  - [Learning and memory in Drosophila: physiologic and genetic bases].
AB  - Elucidation of molecular mechanisms of cognitive functions is one of the major
      achievements in neurobiology. At most, this is due to the studies on the simple
      nervous systems, such as the CNS in Drosophila melanogaster. Many of its
      functional characteristics are pretty similar to higher vertebrates. Among these
      are: 1) evolutionary conservation of genes and molecular systems involved in the
      regulation of learning acquisition and memory formation; 2) presence of highly
      specialized and differentiated sensory, associative and motor centers; 3)
      utilization of similar modes of informational coding and analysis; 4)
      availability of major learning forms including non-associative, as well as
      associative learning; 5) diversity of different memories, including short-term-
      and protein synthesis- dependent long-term memory; 6) presence of aminergic
      reinforcement systems in the brain; 7) feed-back loops of circadian clocks,
      current organism experience and individual organism characters affecting
      cognitive process per se. In this review the main attention is paid to the two
      mostly studied Drosophila learning forms, namely to olfactory Iearning and
      courtship suppression conditioning (CCS). A separate consideration is given to
      the impacts of kynurenins and metabolite of actin remodeling signal cascade.

PMID- 25854116
TI  - [The role of introns in evolution].
AB  - The article describes the role of introns in eukaryotic evolution. Polymorhpsms
      generated in intronic regions included in the reading frame splice isoforms can
      alter the properties of the alternative product. It provides a framework to adapt
      to changing conditions of life. This is the basis for the adaptation of
      eukaryotes to changing conditions of life, that by evolution is fixed at the
      level of populations and species. The article describes the mechanisms of the
      dynamics properties of the eukaryotic genome, and the role of associative
      combinations in the genesis of multifactorial diseases.

PMID- 25854117
TI  - [Functional and phenotypic properties macrophages in acute chronic inflammation.
      Macrophages of sentinel lymph nodes].
AB  - Macrophages are some of key constituents of innate immunity. They possess marked
      phenotypic and functional diversity. Several subpopulations of "classically" and
      "alternatively" activated macrophages have been recognized. Tissue heterogeneity
      of resident macrophages are characterized by great quantity populations of these
      cells in the lymphoid andnonlymphoid tissues. Macrophages actively take part in
      responses of acute and chronic inflammation. An imbalance on the activity of
      these cells leads to cytotoxicity/tissue injury if the balance is tipped toward
      M1 macrophages, and fibrosis/cancer if it is tipped toward M2 macrophages.
      Moreover, macrophages can immediately participate in reactions of innate immunity
      during chronic inflammation.

PMID- 25854119
TI  - Arteriography after embolization before distal pancreatectomy with en bloc celiac
      axis resection.
AB  - OBJECTIVE: To evaluate hemodynamics by arteriographic examinations with and
      without CT in the stomach wall and liver after preoperative embolization to
      redistribute blood flow to the stomach and liver, which is unified to be supplied
      from the superior mesenteric artery, before distal pancreatectomy with en bloc
      celiac axis resection (DP-CAR). MATERIAL AND METHODS: In six patients with
      locally advanced cancer of the pancreatic body in whom DP-CAR was planned, the
      left gastric artery and common hepatic artery were embolized with coils. Celiac
      arteriography and superior mesenteric arteriography with and without CT were
      performed after embolization. RESULTS: In all six patients, intrahepatic arteries
      and the left gastric artery were not visualized on celiac arteriography. On both
      superior mesenteric arteriography and CT obtained while contrast medium was
      infused via the superior mesenteric artery and which was performed immediately
      after embolization procedures, the right gastric artery, gastroepiploic artery,
      gastroduodenal artery, and all hepatic arterial branches were clearly detected.
      Also the distal part of the left gastric artery close to the embolized point was
      detected with at least one of the imaging modalities. CONCLUSION: It was
      clarified radiologically that preoperative embolization results in increased
      blood supply to the stomach wall and liver through the pancreatic arcade.

PMID- 25854118
TI  - Coordinated international action to accelerate genome-to-phenome with FAANG, the
      Functional Annotation of Animal Genomes project.
AB  - We describe the organization of a nascent international effort, the Functional
      Annotation of Animal Genomes (FAANG) project, whose aim is to produce
      comprehensive maps of functional elements in the genomes of domesticated animal
      species. 

PMID- 25854120
TI  - Trends in incidence, primary treatment and survival in chronic myelomonocytic
      leukaemia: a population-based study of 1359 patients diagnosed in the Netherlands
      from 1989 to 2012.

PMID- 25854121
TI  - [Motility disorders of the small intestine].
AB  - Chronic intestinal pseudo-obstruction (CIPO) is the most severe form of
      intestinal motility disorder, which leads to chronic or intermittent symptoms and
      signs of (sub-)ileus despite the absence of an intestinal obstruction. Small
      bowel motility disturbances may occur as primary diseases or secondary to a large
      number of other diseases and disturbances including rheumatological diseases and
      neurotoxic drugs. Pathological alterations affect the nervous system, smooth
      muscles, and/or mesenchymal structures such as the interstitial cells of Cajal or
      glia cells. Clinical symptoms are unspecific so that the initially suspected
      diagnosis is almost always wrong. Thus, extensive and stepwise diagnostic
      procedures are required involving specialized centers in order to exclude
      intestinal obstruction, to search for complications and potential causes of the
      disease, to quantify the extension and severity of the motility disorder, and to
      clarify the pathomechanism if possible. General therapeutic goals include
      maintenance of adequate nutritional status, improvement of propulsive motility,
      amelioration of abdominal symptoms, and avoidance and/or therapy of
      complications. Some CIPO patients require permanent parenteral nutrition. If this
      causes intolerable complications, small bowel transplantation can be considered
      in suitable patients as ultima ratio. 

PMID- 25854122
TI  - [Erratum to: Screening for colorectal, skin, breast and prostate cancer.
      Essential knowledge for counseling].

PMID- 25854123
TI  - Safe transition to surgery: working differently to make blood transfusion process
      safer for elective surgery.
AB  - BACKGROUND: Our institutional policy allows patients who are scheduled for
      elective surgery with no history of a pregnancy or blood transfusion in the
      preceding 3 months to have a presurgical sample (PSS) collected and tested up to
      56 days before their scheduled surgery; however, our PSS TS completion rate in
      eligible patients before the morning of surgery was 83%. In 2011, a team was
      charged to develop a standardized process along with other process improvements
      while ensuring no increase in transfusion-related events. STUDY DESIGN AND
      METHODS: The team followed the DMAIC framework in appraising the effectiveness
      and efficiency of the current state process including baseline data collection
      such as PSS TS completion rate, number of eligible patients needing a PSS TS on
      the day of surgery, benchmarking, SSBO utilization, and future state mapping.
      RESULTS: First quarter (Q1) 2011 versus Q1 2012 postimplementation results showed
      significant improvements of the process including a 53% decrease in PSS TS on the
      day of surgery; a 13% increase in PSS TS completion before the morning of
      surgery; a 26% reduction in total XM RBCs; and a 58.8% reduction in XM RBCs not
      issued, plus a 47% decrease in RBC wastage. Q1 2011 versus Q1 2013 showed a 41%
      reduction in total XM RBCs and an 88.4% reduction in XM RBCs not issued but
      overall RBCs issued versus returned increased slightly and represents a future
      opportunity for improvement. CONCLUSIONS: The redesigned, transformational
      process eliminated SSBO and improved ordering process and PSS TS completion rate
      as well as blood product ordering and utilization.

PMID- 25854124
TI  - Improving access to noninstitutional long-term care for American Indian veterans.
AB  - Home-based primary care (HBPC) is an effective model of noninstitutional long
      term care developed in the Department of Veterans Affairs (VA) to provide ongoing
      care to homebound persons. Significant rural populations of American Indians have
      limited access to services designed for frail older adults. Fourteen Veterans
      Affairs Medical Centers (VAMCs) initiated efforts to expand access to HBPC in
      concert with local tribes and Indian Health Service (IHS) facilities. This study
      characterizes the resulting emerging models of HBPC and co-management. Using an
      observational design, key respondent telephone interviews (n = 37) were conducted
      with stakeholders representing the 14 VAMCs to describe these HBPC programs, and
      HBPC models were evaluated in relation to VAMC organizational culture as revealed
      on the annual VA All Employee Survey. Twelve VAMCs independently developed HBPC
      expansion programs for American Indian veterans, and six different program models
      were implemented. Two models were unique to collaborations between VAMCs and
      tribes; in these collaborations, the tribes retained primary care
      responsibilities. VAMC used the other four models for delivery of care in remote
      rural areas to all veteran populations, American Indians and non-Indians alike.
      Strategies to improve access by reducing geographic barriers occur in all models.
      Comparing mean VAMC organizational culture ratings, as defined in the Competing
      Values Framework, revealed significant group differences for one of these six
      models. Findings from this study illustrate the flexibility of the HBPC program
      and opportunities for co-management and expansion of healthcare access for
      American Indians and non-Indians, particularly in rural areas.

PMID- 25854125
TI  - Six New Polyacetylenic Alcohols from the Marine Sponges Petrosia sp. and
      Halichondria sp.
AB  - Six new polyacetylenic alcohols, termed strongylotriols A and B; pellynols J, K,
      and L; and isopellynol A, together with three known polyacetylenic alcohols,
      pellynols A, B, and C were isolated from the marine sponges Petrosia sp., and
      Halichondria sp. collected in Okinawa, Japan. Their planer structures were
      determined based on 2D-NMR and mass spectrometric analysis of the degraded
      products by RuCl3 oxidation. The absolute stereochemistry of isolates was
      examined by their Mosher's esters. The strongylotriols were found to be optically
      pure compounds, whereas the pellynols are diastereomeric mixtures at the C-6
      position. Proliferation experiments using the HeLa and K562 cell lines suggested
      that the essential structural units for activity are the "hexa-2,4-diyn-1,6-diol"
      and "pent-1-en-4-yn-3-ol" on the termini. 

PMID- 25854126
TI  - Protein-quantum dot nanohybrids for bioanalytical applications.
AB  - Quantum dots (QDs) coupled with biomolecules play an important role as optically
      and chemically stable bioimaging agents for various applications. These inorganic
      biological hybrid conjugates have been demonstrated as powerful fluorescence
      tools for sensing, diagnostics, and labeling. This review focuses on protein-QD
      nanohybrids for different types of bioanalytical applications. There are various
      strategies to modify the surface properties of QDs to produce protein-QD
      nanohybrids that are stable in biological fluids. We expect that multifunctional
      protein-QD nanohybrids can be used as a powerful optical probe for various
      biological applications. WIREs Nanomed Nanobiotechnol 2016, 8:178-190. doi:
      10.1002/wnan.1345 For further resources related to this article, please visit the
      WIREs website. 

PMID- 25854127
TI  - Lung transplantation in Portugal.

PMID- 25854128
TI  - The future of lung transplantation.

PMID- 25854129
TI  - Bronchiectasis: a retrospective study of clinical and aetiological investigation
      in a general respiratory department.
AB  - BACKGROUND: Bronchiectasis can result from many diseases, which makes the
      aetiological investigation a complex process demanding special resources and
      experience. The aetiological diagnosis has been proven to be useful for the
      therapeutic approach. OBJECTIVE: Evaluate how accurately and extensive the
      clinical and aetiological research was for adult bronchiectasis patients in
      pulmonology outpatient service which were not following a pre-existing protocol.
      METHODS: We retrospectively reviewed the records of 202 adult patients with
      bronchiectasis, including the examinations performed to explain the aetiology.
      RESULTS: The mean age of the patients was 54 +/- 15 years, there was a
      predominance of female (63.9%) and non-smoker (70%) patients. Functional
      evaluation showed a mild airway obstruction. The sputum microbiological
      examination was available for 168 patients (43.1% had 3 or more sputum
      examinations during one year). Immunoglobulins and alpha1-antitrypsin were
      measured in around 50% of the patients. The sweat test and the CF genotyping test
      were performed in 18% and 17% of the patients, respectively. The most commonly
      identified cause was post-infectious (30.3%), mostly tuberculosis (27.2%). No
      definitive aetiological diagnosis was established in 57.4% of the patients. We
      achieved a lower aetiological diagnosis if we compare our series with studies in
      which a diagnostic algorithm was applied prospectively. CONCLUSIONS: The general
      characteristics of our patients were similar with other series. Detailed
      investigation of bronchiectasis is not a standard practice in our outpatient
      service. These results suggest that the use of a predefined protocol, based on
      current guidelines, could improve the assessment of these patients and facilitate
      the achievement of a definitive aetiology.

PMID- 25854130
TI  - The overall impact of COPD (CAT) and BODE index on COPD male patients:
      correlation?
AB  - BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) will be the 5th leading
      cause of disability (DALYs) and the 4th leading cause of death by 2030. Measuring
      the real impact of COPD using CAT ("COPD Assessment Test") can complement BODE
      index, an indicator of mortality. AIMS: To assess correlation between CAT and
      BODE index in COPD patients. MATERIALS AND METHODS: A retrospective study was
      conducted in a population of patients with COPD in a Respiratory Rehabilitation
      program. We analyzed demographic variables, variables in respiratory function--6
      min walking test (6 MWT), post-BD forced expiratory volume in 1st second (FEV1%);
      dyspnea by mMRC scale; BODE Index and CAT. RESULTS: The study included 50
      patients--GOLD stage I (7), II (25), III (14) and IV (4), 48 men; mean age 62.6
      years (+/- 9.5), average BMI 25.8 kg/m(2) (+/- 4.8) and FEV1 57.1% (+/- 19.6); 6
      MWT of 443.3m (+/- 61.6); 46% patients in classes 2 and 3 of mMRC scale; 84% were
      class 2 in BODE Index. About 80% reported slight to medium impact in CAT. CAT
      score and impact were correlated with BODE index score: R=0.475, p<0.01, and
      R=0.377, p=0.004, and BODE index class: R=0.357, p=0.011, and R=0.326, p=0.021.
      CONCLUSION: As pre-existent data in the literature (exacerbations and benefit of
      rehabilitation in COPD), the positive correlations found with BODE index
      reinforce the discriminative validity of CAT as a complement in the evaluation of
      what the true impact of COPD is on a patient's daily life.

PMID- 25854131
TI  - Long-term ventilation in children: ten years later.
AB  - INTRODUCTION: Home mechanical ventilation (HMV) represents a treatment option for
      patients with chronic respiratory failure and has changed prognosis and survival
      of many disorders in children. The aim of this study was to characterize a group
      of children on long-term mechanical ventilation (LTMV) for a period longer than
      10 years. METHODS: A retrospective analysis was carried out including patients on
      LTMV for more than 10 years (LTMV-10) in a tertiary pediatric hospital.
      STATISTICAL ANALYSIS: PASW Statistics 18((r)). RESULTS: Thirty-one children (61%
      female) belong to the LTMV-10 group. Median age at the beginning of ventilatory
      support was 3 years (birth to 13 years). Main indications for assisted
      ventilation were neuromuscular disease (n=12, 39%), metabolic disease (n=7, 23%)
      and central hypoventilation (n=6, 19%). Volume ventilation was used in 2
      children, and positive pressure ventilation in the others, mainly bilevel
      positive airway pressure (n=25, 81%). Invasive ventilation via tracheostomy was
      used since the beginning in four cases, and subsequently in two other children.
      The mean time of ventilatory support was 146 months and the maximum was 219
      months. Respiratory morbidity was the most frequent cause of hospitalization and
      the annual rate of such episodes was 0.17 per child. Global mortality rate was
      19%. CONCLUSIONS: HMV programs provide necessary and safe assistance for children
      with severe chronic respiratory failure. As shown in our series, it is possible
      to be kept on this respiratory support modality for long periods with good
      compliance and a small number of hospitalizations.

PMID- 25854132
TI  - Exploratory study comparing dysautonomia between asthmatic and non-asthmatic
      elite swimmers.
AB  - BACKGROUND: Dysautonomia has been independently associated with training and
      exercise-induced bronchoconstriction. In addition, neurogenic airway inflammation
      was recently associated with swimmers-asthma. We aimed to assess the relation
      between autonomic nervous system and airway responsiveness of asthmatic elite
      swimmers. METHODS: Twenty-seven elite swimmers, 11 of whom had asthma, were
      enrolled in this exploratory cross-sectional study. All performed spirometry with
      bronchodilation, skin prick tests and methacholine challenge according to the
      guidelines. Pupillometry was performed using PLR-200TM Pupillometer. One pupil
      light response curve for each eye was recorded and the mean values of pupil's
      maximal and minimal diameters, percentage of constriction, average and maximum
      constriction velocities (parasympathetic parameters), dilation velocity, and
      total time to recover 75% of the initial size (sympathetic parameters) were used
      for analysis. Asthma was defined using IOC-MC criteria; subjects were divided
      into airway hyperesponsiveness (AHR) severity according to methacholine PD20 in:
      no AHR, borderline, mild, moderate and severe AHR. Differences for pupillary
      parameters between groups and after categorization by AHR severity were assessed
      using SPSS 20.0 (p <= 0.05). In individuals with clinically relevant AHR,
      correlation between PD20 and pupillary parameters was investigated with
      Spearman's correlation test. RESULTS: No statistically significant differences
      were observed between asthmatic and non-asthmatic swimmers regarding
      parasympathetic parameters. When stratified by AHR, maximal and minimal diameters
      and percentage of constriction were significantly lower among those with severe
      AHR. Among swimmers with clinically relevant AHR (n = 18), PD20 correlated with
      parasympathetic activity: maximal (r = 0.67, p = 0.002) and minimal diameters (r
      = 0.75, p<0.001), percentage of constriction (r = -0.59, p = 0.011) and latency
      (r = 0.490, p = 0.039). CONCLUSIONS: No significant differences were observed
      between asthmatic and non-asthmatic swimmers regarding parasympathetic
      parameters, but among those with relevant AHR an association was found. Although
      limited by the sample size, these findings support the relation between
      dysautonomia and AHR in asthmatic swimmers.

PMID- 25854133
TI  - Melatonin attenuates lung injury in a hind limb ischemia-reperfusion rat model.
AB  - OBJECTIVE: This study evaluated the protective antioxidant effect of melatonin on
      lung injury as a remote organ after skeletal muscle ischemia-reperfusion in rats.
      METHODS: Thirty male Wistar rats were allocated randomly into three experimental
      groups: operated with no ischemia (Sham) group, ischemia-reperfusion group and
      ischemia-reperfusion+melatonin group. Hind limb ischemia was induced by clamping
      the femoral artery. After 2h ischemia, the clamp was removed and the animal
      underwent 24h reperfusion. Rats in the ischemia-reperfusion + melatonin group
      received melatonin (10 mg/kg i.v.), immediately before the clamp was removed. At
      the end of the trial, animals were euthanized and the lungs were removed for
      water content determination, histopathological and biochemical studies. RESULTS:
      In the ischemia-reperfusion + melatonin group, tissues showed less intense
      histological abnormalities such as neutrophilic infiltration, intra-alveolar
      hemorrhage and edema compared with the ischemia-reperfusion group.
      Histopathologically, there was a significant difference (P < 0.05) between the
      two groups. The lung water content in the ischemia-reperfusion + melatonin group
      was significantly lower than the ischemia-reperfusion group (P < 0.05). Lung
      tissue myeloperoxidase (MPO) activity and nitric oxide (NO) level were
      significantly (P < 0.05) increased by ischemia-reperfusion. The increase in these
      parameters was reduced by melatonin. Comparing the ischemia-reperfusion+melatonin
      group with the sham group, no significant increase in all analyzed aspects of the
      research was observed. CONCLUSIONS: These findings suggest that melatonin has
      preventive effects in lung tissue injury after transient femoral artery
      occlusion.

PMID- 25854134
TI  - Postoperative surgical complications after lung transplantation.
AB  - This is a review article on the main postoperative complications after lung
      transplantation: airways complications, vascular complications, pleural
      complications, surgical wound complications, and abdominal complications.
      Incidence data, severity, and major management regimens are reported.
      Postoperative complications after lung transplantation result in a significantly
      increased morbidity and mortality, with early diagnosis and therapy being
      extremely important. 

PMID- 25854136
TI  - Drug related toxicity in lung transplant recipients.

PMID- 25854135
TI  - Idiopathic pleuroparenchymal fibroelastosis: a rare but increasingly recognized
      entity.
AB  - Idiopathic pleuroparenchymal fibroelastosis (IPPFE) is a recently described rare
      entity, characterized by pleural and subpleural parenchymal fibrosis and
      elastosis mainly in the upper lobes. The etiology and pathophysiology are
      unknown. The prognosis is poor, with no effective therapies other than lung
      transplantation. IPPFE should be properly identified so that it can be approached
      correctly. This report describes two clinical cases with clinical imaging and
      histological features compatible with IPPFE. 

PMID- 25854137
TI  - Nt-ProBNP, Anaemia and Renal function are independent predictors of
      hospitalization in outpatients with pulmonary artery hypertension.

PMID- 25854138
TI  - Evaluation of clinical presentation and outcome of patients with respiratory
      bronchiolitis-associated interstitial lung disease.

PMID- 25854139
TI  - Solitary endobronchial papilloma: a case report.

PMID- 25854142
TI  - The impact of age and race on longevity in pediatric astrocytic tumors: A
      population-based study.
AB  - OBJECTIVE: Despite improvements in pediatric brain tumor outcomes, the survivors
      of childhood brain tumor are burdened by multiple comorbidities. This work
      reports on the relative survival ratios and excess mortality rate in children
      with astrocytic tumors over the past four decades. METHODS: Survival analysis was
      conducted using flexible parametric model to estimate relative survival and
      excess mortality rate for non-white and white children (0-19 years old) using the
      Surveillance, Epidemiology & End Results (SEER) database. We incorporated age
      group and year of diagnosis into the model to estimate these indices for the
      period of 1973-2010. RESULTS: Progressive decline in relative survival ratios was
      noted over time. Non-white children had lower survival rates than white children,
      and these survival patterns persisted over the four-decade span of the study.
      Fifty percent of non-white survivors were deceased 30 years post diagnosis,
      compared to 35 years in white survivors. CONCLUSIONS: Survivors of childhood
      brain tumors have progressively lower survival rates as they get older, and this
      is higher in non-white when compared to white children. Future research efforts
      need to focus on understanding the factors mediating the effect of the tumor or
      its treatment on survival in these patients, and the ethnic variations that
      derive these survival trends.

PMID- 25854140
TI  - Issues in the Diagnosis and Treatment of Primary Aldosteronism.
AB  - Primary aldosteronism (PA) is associated with a high rate of cardio- and
      cerebrovascular complications and metabolic alterations. PA is also recognized as
      the most frequent, although often unrecognized, secondary form of hypertension.
      Guidelines have been released to assist clinicians in the diagnostic work-up and
      subtype differentiation of PA. In this review we discuss and compare the
      available guidelines in the context of our professional experience and evaluate
      diagnostic and therapeutic aspects that are still a matter of debate. 

PMID- 25854143
TI  - Management of cancer-associated disseminated intravascular coagulation: guidance
      from the SSC of the ISTH: reply.

PMID- 25854144
TI  - In silico analyses of missense mutations in coagulation factor VIII:
      identification of severity determinants of haemophilia A.
AB  - Factor VIII (FVIII) mutations cause haemophilia A (HA), an X-linked recessive
      coagulation disorder. Over 1000 missense mutations in FVIII are known and they
      lead to variable clinical phenotypes (severe, moderate and mild). The exact
      molecular basis of this phenotypic heterogeneity by FVIII missense mutations is
      elusive to date. In this study, we aimed to identify the severity determinants
      that cause phenotypic heterogeneity of HA. We compiled and curated a data set of
      766 missense mutations from the repertoire of missense mutations in FVIII. We
      analysed these mutations by computational programs (e.g. Swiss-PdbViewer) and
      different mutation analysis servers (e.g. SIFT, PROVEAN, CUPSAT, PolyPhen2,
      MutPred); and various sequence- and structure-based parameters were assessed for
      any significant distribution bias among different HA phenotypes. Our analyses
      suggest that 'mutations in evolutionary conserved residues', 'mutations in buried
      residues', mutation-induced 'steric clash' and 'surface electrostatic potential
      alteration' act as risk factors towards severe HA. We have developed a grading
      system for FVIII mutations combining the severity determinants, and the grading
      pattern correlates with HA phenotype. This study will help to correctly associate
      the HA phenotype with a mutation and aid early characterization of novel
      variants. 

PMID- 25854145
TI  - Synthesis and evaluation of derivatives of the proteasome deubiquitinase
      inhibitor b-AP15.
AB  - The ubiquitin-proteasome system (UPS) is increasingly recognized as a therapeutic
      target for the development of anticancer therapies. The success of the 20S
      proteasome core particle (20S CP) inhibitor bortezomib in the clinical management
      of multiple myeloma has raised the possibility of identifying other UPS
      components for therapeutic intervention. We previously identified the small
      molecule b-AP15 as an inhibitor of 19S proteasome deubiquitinase (DUB) activity.
      Building upon our previous data, we performed a structure-activity relationship
      (SAR) study on b-AP15 and identified VLX1570 as an analog with promising
      properties, including enhanced potency and improved solubility in aqueous
      solution. In silico modeling was consistent with interaction of VLX1570 with key
      cysteine residues located at the active sites of the proteasome DUBs USP14 and
      UCHL5. VLX1570 was found to inhibit proteasome deubiquitinase activity in vitro
      in a manner consistent with competitive inhibition. Furthermore, using active
      site-directed probes, VLX1570 also inhibited proteasome DUB activity in exposed
      cells. Importantly, VLX1570 did not show inhibitory activity on a panel of
      recombinant non-proteasome DUBs, on recombinant kinases, or on caspase-3
      activity, suggesting that VLX1570 is not an overtly reactive general enzyme
      inhibitor. Taken together, our data shows the chemical and biological properties
      of VLX1570 as an optimized proteasome DUB inhibitor. 

PMID- 25854146
TI  - Monofluorination of Organic Compounds: 10 Years of Innovation.

PMID- 25854149
TI  - Novel Advances in the Association Between Helicobacter pylori Infection,
      Metabolic Syndrome, and Related Morbidity.

PMID- 25854147
TI  - Processing of visually evoked innate fear by a non-canonical thalamic pathway.
AB  - The ability of animals to respond to life-threatening stimuli is essential for
      survival. Although vision provides one of the major sensory inputs for detecting
      threats across animal species, the circuitry underlying defensive responses to
      visual stimuli remains poorly defined. Here, we investigate the circuitry
      underlying innate defensive behaviours elicited by predator-like visual stimuli
      in mice. Our results demonstrate that neurons in the superior colliculus (SC) are
      essential for a variety of acute and persistent defensive responses to overhead
      looming stimuli. Optogenetic mapping revealed that SC projections to the lateral
      posterior nucleus (LP) of the thalamus, a non-canonical polymodal sensory relay,
      are sufficient to mimic visually evoked fear responses. In vivo electrophysiology
      experiments identified a di-synaptic circuit from SC through LP to the lateral
      amygdale (Amg), and lesions of the Amg blocked the full range of visually evoked
      defensive responses. Our results reveal a novel collicular-thalamic-Amg circuit
      important for innate defensive responses to visual threats. 

PMID- 25854150
TI  - [Lupus therapy on the move : The direction is right!].

PMID- 25854148
TI  - Genetic disruption of Smad7 impairs skeletal muscle growth and regeneration.
AB  - KEY POINTS: Smad7 is an intracellular antagonist of transforming growth factor
      beta signalling pathways and modulates muscle growth in vivo. Loss of Smad7
      results in decreased muscle mass, reduced force generation, fibre type switching
      from glycolytic towards oxidative type and delayed recovery from injury.
      Upregulated Smad2/3 signalling in Smad7(-/-) muscle results in reduced myoblast
      proliferation and differentiation. Smad7 is an important regulator of muscle
      growth and may be a potential intracellular therapeutic target for muscle
      disorders. ABSTRACT: The transforming growth factor-beta (TGF-beta) family of
      growth factors plays an essential role in mediating cellular growth and
      differentiation. Myostatin is a muscle-specific member of the TGF-beta
      superfamily and a negative regulator of muscle growth. Myostatin inhibitors are
      currently being pursued as therapeutic options for muscle disorders. Smad7
      inhibits intracellular myostatin signalling via Smad2/3, and thus presents a
      means of regulating myostatin and potentiating muscle growth. We investigated the
      functional loss of Smad7 on muscle in vivo by examining muscle growth and
      differentiation in mice deficient in Smad7 (Smad7(-/-) ). Smad7(-/-) mice showed
      reduced muscle mass, hypotrophy and hypoplasia of muscle fibres, as well as an
      increase in oxidative fibre types. Examination of muscle strength showed reduced
      force generation in vivo and ex vivo compared to wild-type controls. Analysis of
      muscle regeneration showed a delay in recovery, probably as a result of decreased
      activation, proliferation and differentiation of satellite cells, as confirmed in
      vitro. Additionally, myostatin expression was upregulated in Smad7(-/-) muscle.
      Our findings suggest that increased Smad2/3 signalling in the absence of Smad7
      inhibition impedes muscle growth and regeneration. Taken together, our
      experiments demonstrate that Smad7 is an important mediator of muscle growth in
      vivo. Our studies enhance our understanding of in vivo TGF-beta pathway
      modulation and suggest that Smad7 may be an important therapeutic target for
      muscle disorders.

PMID- 25854151
TI  - [Pathogenesis of systemic lupus erythematosus].
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease with an extremely
      complex pathogenesis. Due to a genetic predisposition the disease can be induced
      by multiple stress factors involving epigenetic mechanisms and under the
      influence of the innate immune system. Defective clearance of immune complexes
      and apoptotic material together with enhanced neutrophil extracellular trap
      formation (NETosis) as well as up-regulation of type 1 interferon in particular,
      drive the adaptive immune system to a breakdown of self-tolerance. The result is
      a B cell hyperactivity, which leads to the generation of a multitude of different
      autoantibodies that are not only directed against nuclear antigens.
      Autoantibodies are the initiators for the involvement of many organs, which
      enhances further inflammatory cells and cytokines by participation of effector T
      cells. Finally, an autoreactive immunological (plasma cell) memory is formed,
      which contributes to chronification and is associated with therapy-refractive
      courses of the disease. The depletion of the autoreactive immunological memory by
      immunoablation can lead to induction of self-tolerance and long-term remission. 

PMID- 25854152
TI  - [Antiphospholipid syndrome].
AB  - PATHOGENESIS AND CLINICAL ASPECTS: Antiphospholipid syndrome (APS) is
      characterized by recurrent arterial or venous thromboembolism or pregnancy loss
      in association with antibodies directed against anionic phospholipids or against
      plasma proteins bound to anionic phospholipids. It occurs in 15-30 % of patients
      suffering from systemic lupus erythematosus (secondary APS) but can also occur
      without an underlying connective tissue disease (primary APS). The reason for the
      huge variety of clinical manifestations is thromboembolic vaso-occlusive disease
      and not vasculitis in blood vessels of different sizes and sites (e.g. deep vein
      thrombosis, pulmonary embolism and cerebrovascular disease). Accordingly, fetal
      abortion is also caused by infarctions of blood vessels in the placenta typically
      after the tenth week of gestation. DIAGNOSTICS: Establishing the correct
      diagnosis of APS is not easy. Diagnosis should not rely on only slightly or
      temporarily elevated levels of AP antibodies as thrombosis might occur due to
      other reasons even in patients with AP antibodies. The estimation of the risk of
      thrombotic complications as well as the type and intensity of a suitable
      anticoagulation prophylaxis are challenging in the treatment of patients with
      APS. THERAPY: Antiplatelet agents (aspirin), heparin and vitamin K antagonists
      are used for therapy. Immunosuppression is not effective for the prevention of
      thromboembolic complications; therefore, not only problem issues on laboratory
      diagnostics but also current therapeutic recommendations are presented.

PMID- 25854153
TI  - [Erratum to: Relapsing polychondritis. Primary and follow-up diagnostics with
      (18)F-FDG-PET/CT].

PMID- 25854154
TI  - [Therapeutic strategies for systemic lupus erythematosus].
AB  - Therapeutic strategy means the definition of a long-term target, which should be
      reached by a chosen management. As for rheumatoid arthritis, the treat to target
      initiative recommends remission as the target for systemic lupus erythematosus
      (SLE) but the command variables of remission are not yet defined. The basis of a
      therapeutic strategy is first the analysis of those factors that may influence
      the achievement of the objectives: SLE disease activity, the differentiation of
      damage, organ manifestations, comorbidities, genetics, sex, age of onset and
      considering the pathophysiological basis are some of these factors. The next step
      is the analysis of the available substances and concepts that allow the target to
      be reached. Finally, rules for management (e.g. guidelines) are needed that
      enrich the possibility to reach the target and improve the prognosis of patients
      suffering from SLE. 

PMID- 25854155
TI  - [Biologics therapy for systemic lupus erythematosus. Current situation].
AB  - BACKGROUND: Improved understanding of the immunopathogenesis of systemic lupus
      erythematosus (SLE) has paved the way for new specific immune interventions for
      this inflammatory disease similar to those for rheumatoid arthritis and
      spondylarthritides. METHODS: New biologics were developed on this basis or are in
      the process of clinical development and open up new therapy options for patients.
      In this context belimumab is of particular importance. As an innovative biologic
      the monoclonal antibody against the cytokine BAFF/BLyS (belimumab) has been
      approved for the treatment of serologically active SLE. A number of other
      biologics against other cytokines are in the clinical development phase and
      appear to be promising for further improvement of the current therapeutic
      possibilities in SLE. This article addresses the current aspects of immune
      interventions with biologics for SLE and the specific challenges of this disease.

PMID- 25854156
TI  - [Lumbar spinal stenosis. From diagnosis to correct therapy].
AB  - The number of patients with a diagnosis of lumbar spinal stenosis (LSS) is
      steadily increasing and the expectations of patients are high; however, valid
      data for an appropriate therapy are lacking. Treatment is mostly the result of
      the surgeon's experience and the clinical focus. The findings in magnetic
      resonance imaging (MRI) often do not correlate with the patient's symptoms. It is
      proposed that treatment should start with a conservative multimodal approach.
      Increased pain with neurogenic claudication symptoms under conservative treatment
      should be treated surgically. Absolute indications for surgery, such as a conus
      cauda syndrome are rare. The goal of all surgical procedures is to decompress the
      spinal canal without compromising the stability of the motion segment. This can
      also make an additional fusion necessary. 

PMID- 25854157
TI  - [Molecular effects of physical therapy. What's new?].
AB  - Modern molecular medicine offers the possibility to investigate the potential
      influences of different methods of physical therapy on pivotal mechanisms and
      mediators of the inflammatory processes of rheumatic diseases and interactions
      between cells of the immune system and bone. Based on recent studies, it could be
      shown that modulation of these regulatory systems can be achieved by various
      physiotherapeutics. 

PMID- 25854158
TI  - [B cell therapy of rheumatoid arthritis with rituximab. Practice-relevant aspects
      for the routine].
AB  - BACKGROUND: B cells play a key role in the pathogenesis of various rheumatic
      autoimmune diseases and have therefore become an important therapeutic target.
      Rituximab is a chimeric monoclonal anti-CD20 antibody that induces a nearly
      complete, transient depletion of peripheral CD20-positive B cells. In 2006
      rituximab received approval for use in patients with rheumatoid arthritis (RA)
      and in 2013 for patients with antineutrophil cytoplasmic antibody (ANCA)
      associated vasculitis granulomatosis with polyangiitis (GPA) and microscopic
      polyangiitis (MPA). OBJECTIVES: In this review various clinically relevant
      aspects of B cell therapy in RA patients are discussed, including its role in the
      therapeutic algorithm as well as data on long-term efficacy and safety.

PMID- 25854159
TI  - Polymorphisms of MMP-1 and MMP-3 and susceptibility to rheumatoid arthritis. A
      meta-analysis.
AB  - OBJECTIVE: To determine the correlation between rheumatoid arthritis (RA) and
      polymorphisms of the matrix metalloproteinase (MMP) genes MMP-1 and MMP-3.
      BACKGROUND: The 1607 1G/2G and 1171 5A/6A polymorphisms of MMP genes MMP-1 and
      MMP-3 have been discovered to be functional, and may be conducive to RA. In order
      to determine whether MMP-1 and MMP-3 gene polymorphisms correlate with RA
      development, we performed a meta-analysis to further validate the function of
      these polymorphisms in RA. METHODS: We searched PubMed, ISI Web of Knowledge,
      MEDLINE, Embase, Google Scholar Chinese Biomedical Literature Database, and
      Wanfang Data to identify all published case-control studies on the MMP-1-1607
      1G/2G and MMP-3-1171 5A/6A polymorphisms and RA risk. Odds ratios (OR) and 95 %
      confidence intervals (CI) were used to estimate the association between these
      polymorphisms and RA risk. RESULTS: After being assessed, five articles fulfilled
      the inclusion criteria. To assess associations, the pooled OR with 95 % CIs was
      calculated. Neither the MMP-1-1607 1G/2G nor the MMP-3-1171 5A/6A polymorphism
      was statistically associated with RA in any of the five models, nor in the
      subgroup analysis models of MMP-3-1171 5A/6A in Caucasian and Asian patients.
      CONCLUSION: Our study suggests that MMP-1 and MMP-3 polymorphisms have no
      significant association with the risk of RA.

PMID- 25854160
TI  - GC-MS analysis of bioactive components and synthesis of gold nanoparticle using
      Chloroxylon swietenia DC leaf extract and its larvicidal activity.
AB  - A rapid bio-reduction of chloroauric acid (HAuCl4) was achieved by Chloroxylon
      swietenia DC leaf extract (CSLE), which resulted in the formation of well
      dispersed C. swietenia gold nanoparticles (CSGNPs). The formation of GNPs was
      confirmed by color changes from yellowish green to purple and their
      characteristic peak at 545 nm. The characterization of synthesized CSGNPs was
      made through X-ray diffraction (XRD), fourier transform infrared spectroscopy
      (FTIR), high resolution transmission electron microscopy (HRTEM) equipped with
      energy dispersive X-ray spectroscopy (EDX) followed by size and zeta potential
      analyses. The GC-MS profile of C. swietenia methanolic leaf extract (CSMLE)
      resulted 20 phytocomponents, among those heptacosanoic acid, 25-methyl-, methyl
      ester (C29H58O2) attributes highest peak area. The efficiency of the synthesized
      CSMLE, CSGNPs and CSLE were tested against fourth instar larvae of malarial and
      dengue vector, which resulted more substantial upshot than with leaf extract
      treated. The Lethal concentration (LC50) values of CSMLE, CSGNPs and CSLE were
      found to be 0.509, 0.340, 0.423 ppm and 0.602, 0.188, 0.646 ppm on Aedes aegypti
      and Anopheles stephensi, respectively. The findings form an important baseline
      information proceeding biologically innocuous biopesticide for controlling the
      malarial and dengue vectors.

PMID- 25854161
TI  - Spectroscopy and Dynamics of K Atoms on Argon Clusters.
AB  - We present a combined experimental and simulation study of the 4s -> 4p
      photoexcitation of the K atom trapped at the surface of ArN clusters made of a
      few hundred Ar atoms. Our experimental method based on photoelectron spectroscopy
      allows us to firmly establish that one single K atom is trapped at the surface of
      the cluster. The absorption spectrum is characterized by the splitting of the
      atomic absorption line into two broad bands, a Pi band associated with p orbitals
      parallel to the cluster surface and a Sigma band associated with the
      perpendicular orientation. The spectrum is consistent with observations reported
      for K atoms trapped on lighter inert gas clusters, but the splitting between the
      Pi and Sigma bands is significantly larger. We show that a large amount of K
      atoms are transiently stuck and eventually lost by the Ar cluster, in contrast
      with previous observations reported for alkaline earth metal systems. The
      excitation in the Sigma band leads systematically to the ejection of the K atom
      from the Ar cluster. On the contrary, excitation in the Pi band leads to the
      formation of a bound state. In this case, the analysis of the experimental
      photoelectron spectrum by means of nonadiabatic molecular dynamics simulation
      shows that the relaxation drives the system toward a basin where the coordination
      of the K atom is 2.2 Ar atoms on the average, in a poorly structured surface. 

PMID- 25854162
TI  - Self-diffusion and interactions in mixtures of imidazolium bis(mandelato)borate
      ionic liquids with polyethylene glycol: (1) H NMR study.
AB  - We used (1) H nuclear magnetic resonance pulsed-field gradient to study the self
      diffusion of polyethylene glycol (PEG) and ions in a mixture of PEG and
      imidazolium bis(mandelato)borate ionic liquids (ILs) at IL concentrations from 0
      to 10 wt% and temperatures from 295 to 370 K. PEG behaves as a solvent for these
      ILs, allowing observation of separate lines in (1) H NMR spectra assigned to the
      cation and anion as well as to PEG. The diffusion coefficients of PEG, as well as
      the imidazolium cation and bis(mandelato)borate (BMB) anion, differ under all
      experimental conditions tested. This demonstrates that the IL in the mixture is
      present in at least a partially dissociated state, while the lifetimes of the
      associated states of the ions and ions with PEG are less than ~30 ms. Generally,
      increasing the concentration of the IL leads to a decrease in the diffusion
      coefficients of PEG and both ions. The diffusion coefficient of the anion is less
      than that of the cation; the molecular mass dependence of diffusion of ions can
      be described by the Stokes-Einstein model. NMR chemical shift alteration analysis
      showed that the presence of PEG changes mainly the chemical shifts of protons
      belonging to imidazole ring of the cation, while chemical shifts of protons of
      anions and PEG remain unchanged. This demonstrated that the imidazolium cation
      interacts mainly with PEG, which most probably occurs through the oxygen of PEG
      and the imidazole ring. The BMB anion does not strongly interact with PEG, but it
      may be indirectly affected by PEG through interaction with the cation, which
      directly interacts with PEG.

PMID- 25854163
TI  - MRTF-A and STAT3 promote MDA-MB-231 cell migration via hypermethylating BRSM1.
AB  - Breast cancer is the leading cause of cancer death in women worldwide which is
      closely related to metastasis. But the exact molecular mechanism of metastasis is
      still not fully understood. We now report that both MRTF-A and STAT3 play
      important roles in migration of MDA-MB-231 breast cancer cells. Moreover, MRTF-A
      and STAT3 synergistically increased MDA-MB-231 cell migration by promoting the
      expression of migration markers urokinase-type plasminogen activator (uPA) and
      osteopontin (OPN) and inhibiting the expression of breast cancer metastasis
      suppressor 1 (BRMS1). Luciferase reporter assays demonstrated that MRTF-A and
      STAT3 do not affect transcription of the BRMS1 promoter. Instead, we identified a
      newly molecular mechanism by which MRTF-A and STAT3 synergistically controlled
      MDA-MB-231 cell migration by recruiting DNMT1 to hypermethylate the promoter of
      BRMS1 and thus affect the expression of BRMS1. Interestingly, physical
      interaction between MRTF-A and STAT3 synergistically promotes the transactivity
      of DNMT1 by binding to the GAS element within the DNMT1 promoter. Our data thus
      provide important and novel insights into the roles of MRTF-A and STAT3 in
      regulating MDA-MB-231 cell migration.

PMID- 25854164
TI  - In silico optimization of pharmacokinetic properties and receptor binding
      affinity simultaneously: a 'parallel progression approach to drug design' applied
      to beta-blockers.
AB  - The present work exploits the potential of in silico approaches for minimizing
      attrition of leads in the later stages of drug development. We propose a
      theoretical approach, wherein 'parallel' information is generated to
      simultaneously optimize the pharmacokinetics (PK) and pharmacodynamics (PD) of
      lead candidates. beta-blockers, though in use for many years, have suboptimal
      PKs; hence are an ideal test series for the 'parallel progression approach'. This
      approach utilizes molecular modeling tools viz. hologram quantitative structure
      activity relationships, homology modeling, docking, predictive metabolism, and
      toxicity models. Validated models have been developed for PK parameters such as
      volume of distribution (log Vd) and clearance (log Cl), which together influence
      the half-life (t1/2) of a drug. Simultaneously, models for PD in terms of
      inhibition constant pKi have been developed. Thus, PK and PD properties of beta
      blockers were concurrently analyzed and after iterative cycling, modifications
      were proposed that lead to compounds with optimized PK and PD. We report some of
      the resultant re-engineered beta-blockers with improved half-lives and pKi values
      comparable with marketed beta-blockers. These were further analyzed by the
      docking studies to evaluate their binding poses. Finally, metabolic and
      toxicological assessment of these molecules was done through in silico methods.
      The strategy proposed herein has potential universal applicability, and can be
      used in any drug discovery scenario; provided that the data used is consistent in
      terms of experimental conditions, endpoints, and methods employed. Thus the
      'parallel progression approach' helps to simultaneously fine-tune various
      properties of the drug and would be an invaluable tool during the drug
      development process. 

PMID- 25854165
TI  - The influence of FRCs reinforcement on marginal adaptation of CAD/CAM composite
      resin endocrowns after simulated fatigue loading.
AB  - To evaluate the marginal adaptation of endodontically treated molars restored
      with CAD/CAM composite resin endocrowns either with or without reinforcement by
      fibre reinforced composites (FRCs), used in different configurations. 32 human
      endodontically treated molars were cut 2 mm over the CEJ. Two interproximal boxes
      were created with the margins located 1 mm below the CEJ (distal box) and 1 mm
      over the CEJ (mesial box). All specimens were divided in four groups (n = 8). The
      pulp chamber was filled with: group 1 (control), hybrid resin composite (G-aenial
      Posterior, GC); group 2, as group 1 but covered by 3 meshes of E-glass fibres
      (EverStick NET, Stick Tech); group 3, FRC resin (EverX Posterior, GC); group 4,
      as group 3 but covered by 3 meshes of E-glass fibres. The crowns of all teeth
      were restored with CAD/CAM composite resin endocrowns (LAVA Ultimate, 3M). All
      specimens were thermo-mechanically loaded in a computer-controlled chewing
      machine (600,000 cycles, 1.6 Hz, 49 N and simultaneously 1500 thermo-cycles, 60
      s, 5-55  degrees C). Marginal analysis before and after the loading was carried
      out on epoxy replicas by SEM at 200* magnification. For all the groups, the
      percentage values of perfect marginal adaptation after loading were always
      significantly lower than before loading (p < 0.05). The marginal adaptation
      before and after loading was not significantly different between the experimental
      groups (p > 0.05). Within the limitations of this in vitro study, the use of FRCs
      to reinforce the pulp chamber of devitalized molars restored with CAD/CAM
      composite resin restorations did not significantly influenced their marginal
      quality.

PMID- 25854166
TI  - Highly efficient semitransparent polymer solar cells with color rendering index
      approaching 100 using one-dimensional photonic crystal.
AB  - Window application is the important aim for semitransparent solar cells (STPSC)
      investigation. Here, we demonstrate a method to achieve significantly improved
      color rendering index (CRI), depressed chromaticity difference (DC), and enhanced
      power conversion efficiency (PCE) simultaneously by introducing the one
      dimensional photonic crystals (1DPCs) Bragg reflector structure onto the STPSC.
      The device performance is studied from aspects of color perception, electrical
      properties, and theoretical optical simulations. The STPSCs exhibit achromatic
      transparency nature color perceptions, especially for the STPSCs with 1DPCs
      (pairs >= 3) under AM 1.5G illumination light source, standard illuminant D65,
      and standard illuminant A. The excellent CRI is approaching 97 with lower DC
      about 0.0013 for the device with 5 pairs of 1DPC illumined by AM 1.5G
      illumination light source. At the same time, the PCE of STPSC devices with 5
      pairs of 1DPC was improved from 4.87 +/- 0.14% to 5.31 +/- 0.13% compared to
      without. This method provides a facilitative approach to realizing excellent
      SPTSC window application. 

PMID- 25854167
TI  - Expression of colony-stimulating factor 1 is associated with occurrence of
      osteochondral change in pigmented villonodular synovitis.
AB  - Pigmented villonodular synovitis (PVNS) is a benign, translocation-derived
      neoplasm. Because of its high local recurrence rate after surgery and occurrence
      of osteochondral destruction, a novel therapeutic target is required. The present
      study aimed to evaluate the significance of protein expression possibly
      associated with the pathogenesis during the clinical course of PVNS. In 40 cases
      of PVNS, positivity of colony-stimulated factor 1 (CSF1), its receptor (CSF1R),
      and receptor activator of nuclear factor kappa-B ligand (RANKL) were
      immunohistochemically determined. The relationship between the positivity and
      clinical outcomes was investigated. High positivity of CSF1 staining intensity
      was associated with an increased incidence of osteochondral lesions (bone erosion
      and osteoarthritis) (p = 0.009), but not with the rate of local recurrence.
      Positivity of CSF1R and RANKL staining was not associated with any clinical
      variables. The number of giant cells was not correlated with positivity of any of
      the three proteins, or with the clinical outcome. Focusing on knee cases, CSF1
      positivity was also associated with the incidence of osteochondal change (p =
      0.02). CSF1R positivity was high in cases which had local recurrence, but not
      significantly so (p = 0.129). Determination of CSF1 and CSF1R expression may be
      useful as a prognosticator of the clinical course and/or outcomes of PVNS.

PMID- 25854168
TI  - Assessment of BRAFV600E and SMOF412E mutations in epithelial odontogenic tumours.
AB  - The classification of ameloblastoma in multicystic or unicystic variants is
      associated with its clinical behaviour. Recently, BRAF and SMO mutations have
      been reported in ameloblastomas. However, it is not clear if such mutations are
      shared by the multi- and unicystic variants of ameloblastoma or by odontogenic
      carcinomas. We assessed BRAFV600E and SMOF412E in multicystic, unicystic and
      desmoplastic ameloblastomas. In addition, we investigated whether the BRAFV600E
      mutation occurs in odontogenic carcinomas. A total of 28 formalin-fixed paraffin
      embedded samples, comprising 17 ameloblastomas and 11 odontogenic carcinomas,
      were included. The BRAFV600E mutation was assessed by real-time PCR with a
      specific TaqMan probe and confirmed by Sanger sequencing. The SMOF412E mutation
      was assessed by Sanger sequencing. Fourteen out of 17 (82 %) ameloblastomas
      showed the BRAFV600E mutation, specifically, 5/6 (83 %) unicystic, 7/9 (78 %)
      multicystic and 2/2 desmoplastic ameloblastomas. BRAFV600E mutation was detected
      in 4/11 (36 %) malignant tumours, specifically, 3/8 (38 %) ameloblastic
      carcinomas and 1/1 clear cell odontogenic carcinoma, while the two ghost cell
      odontogenic carcinomas did not harbour this mutation. The SMOF412E mutation was
      not detected in ameloblastoma. The BRAFV600E-activating mutation is a common
      event in ameloblastomas, occurring regardless of site or histological type. This
      mutation is also detected in odontogenic carcinomas. SMO somatic mutation is a
      secondary genetic event in the ameloblastoma pathogenesis. Our findings support
      the possibility for personalised, molecular-targeted therapy for ameloblastomas
      and odontogenic carcinomas harbouring the BRAFV600E mutation.

PMID- 25854169
TI  - Metformin inhibits thyroid cancer cell growth, migration, and EMT through the
      mTOR pathway.
AB  - Mammalian target of rapamycin (mTOR) signaling pathways have been shown to be
      activated in thyroid cancer. Recent evidences have demonstrated that the
      antidiabetic agent metformin, an activator of 5'-AMP-activated protein kinase,
      can impair the proliferation and migration of cancer cells via inhibition of
      mTOR. However, the underlying mechanisms remain unclear. In this study, we show
      that metformin can inhibit mTOR pathway to impair growth and migration of the
      thyroid cancer cell lines. Cyclin D1 and c-Myc are important regulators of cancer
      cell growth, and we observed that treatment of thyroid cancer cells with
      metformin reduced c-Myc and cyclin D1 expression through suppression of mTOR and
      subsequent inhibition of P70S6K1 and 4E-BP1 phosphorylation. Metformin reduced
      epithelial to mesenchymal transition (EMT) in thyroid carcinoma cells. Moreover,
      metformin regulated expression of the EMT-related markers E-cadherin, N-cadherin,
      and Snail. Additionally, knockdown of TSC2, the upstream regulatory molecule of
      mTOR pathway, or treatment of rapamycin, the mTOR inhibitor, could abolish the
      effects of metformin to regulate thyroid cancer cell proliferation, migration,
      EMT, and mTOR pathway molecules. These results indicate that metformin can
      suppress the proliferation, migration, and EMT of thyroid cancer cell lines by
      inhibiting mTOR signaling. These findings suggest that metformin and its
      molecular targets may be useful in thyroid carcinoma therapy. 

PMID- 25854170
TI  - Diagnostic accuracy of cytokeratin-19 fragment (CYFRA 21-1) for bladder cancer: a
      systematic review and meta-analysis.
AB  - Previous studies have evaluated the accuracy of serum and urinary measurements of
      cytokeratin-19 fragment (CYFRA 21-1) for the diagnosis of bladder cancer;
      however, the results have been inconsistent. The aim of this study was to
      evaluate the overall accuracy of CYFRA 21-1 for the diagnosis of bladder cancer.
      We performed a search for English-language publications reporting on the
      detection of CYFRA21-1 levels for the diagnosis of bladder cancer through
      November 2, 2014, using public medical databases, including EMBASE, Web of
      Science, and Medline. The quality of the studies was assessed by revised QUADAS
      tools. The performance characteristics were pooled and analyzed using a bivariate
      model. Publication bias was explored with the Deek's test. Sixteen studies, with
      a total 1,262 bladder-cancer patients and 1,233 non-bladder-cancer patients, were
      included in the study. The pooled sensitivities for serum and urine CYFRA 21-1
      were 0.42 (95 % confidence interval (CI), 0.33-0.51) and 0.82 (95 % CI, 0.70
      0.90), respectively. The corresponding specificities were 0.94 (95 % CI, 0.90
      0.96) and 0.80 (95 % CI, 0.73-0.86), respectively. The areas under the summary
      receiver-operating-characteristic curves for serum and urine CYFRA 21-1 were 0.88
      (95 % CI, 0.85-0.91) and 0.87 (95 % CI, 0.84-0.90), respectively. The major
      design deficiencies of the included studies were participant-selection bias,
      potential review, and verification bias. Therefore, we concluded that both serum
      and urine CYFRA 21-1 served as efficient indexes for bladder-cancer diagnosis.
      Additional, well-designed studies should be performed to rigorously evaluate the
      diagnostic value of CYFRA 21-1 for bladder cancer.

PMID- 25854171
TI  - Clinical pathological characteristics of breast cancer patients with secondary
      diabetes after systemic therapy: a retrospective multicenter study.
AB  - The objective of this study was to investigate the clinical pathological
      characteristics of breast cancer (BC) patients with secondary diabetes after
      systemic therapy without preexisting diabetes. A total of 1434 BC patients
      received systemic therapy and were analyzed retrospectively. Fasting plasma
      glucose (FPG) levels were monitored prior to the treatments, during the course of
      systemic therapy, and at the follow-up visits. Cox regression models were used to
      estimate the associations between the clinical pathological characteristics of BC
      and the cause-specific hazard of developing secondary diabetes. Among the 1434 BC
      patients, 151 had preexisting type 2 diabetes. Of the remaining 1283 patients
      with normal FPG levels prior to the systemic therapy, 59 developed secondary
      diabetes and 72 displayed secondary impaired fasting glucose (IFG) over a mean
      follow-up of 41 months. The prevalence of secondary type 2 diabetes in BC
      patients was 4.6 % (59/1283), which was obviously higher than that of the normal
      control group (1.4 %, P < 0.001). The percentage of older patients (P < 0.05),
      menopausal patients (P < 0.001), and obese patients (P < 0.01) tended to be lower
      in the secondary diabetic group. In addition, these patients with secondary
      diabetes had later pathological stages (P < 0.01), more lymph node metastasis (P
      < 0.05), negative estrogen receptor (ER) expression (P < 0.05), and smaller size
      of tumors (P < 0.05). After adjusting for age and BMI, the risk of developing
      secondary diabetes and IFG in subjects with later pathological stage BC (hazard
      ratio (HR) = 1.623; 95 % confidence interval (CI) 1.128-2.335 (P < 0.01)),
      negative progesterone receptor (PR) expression (HR = 0.530; 95 % CI 0.372-0.755
      (P < 0.001)), positive human epidermal growth factor receptor 2 (HER2) expression
      (HR = 1.822; 95 % CI 1.230-2.700 (P < 0.01)), and more lymph node metastasis (HR
      = 1.595; 95 % CI 1.128-2.258 (P < 0.01)) was significantly higher. In conclusion,
      this study shows that an increase in the incidence of diabetes among breast
      cancer survivors after systemic therapy, especially the patients with later
      pathological stages, more lymph node metastasis, negative hormone receptor
      expression, and positive HER2 expression. Our study suggests that greater
      diabetes screening and prevention strategies among breast cancer patients after
      systemic treatment are needed in China.

PMID- 25854172
TI  - Polymorphisms in the kinesin-like factor 1 B gene and risk of epithelial ovarian
      cancer in Eastern Chinese women.
AB  - The kinesin-like factor 1 B (KIF1B) gene plays an important role in the process
      of apoptosis and the transformation and progression of malignant cells. Genetic
      variations in KIF1B may contribute to risk of epithelial ovarian cancer (EOC). In
      this study of 1,324 EOC patients and 1,386 cancer-free female controls, we
      investigated associations between two potentially functional single nucleotide
      polymorphisms in KIF1B and EOC risk by the conditional logistic regression
      analysis. General linear regression model was used to evaluate the correlation
      between the number of variant alleles and KIF1B mRNA expression levels. We found
      that the rs17401966 variant AG/GG genotypes were significantly associated with a
      decreased risk of EOC (adjusted odds ratio (OR) = 0.81, 95 % confidence interval
      (CI) = 0.68-0.97), compared with the AA genotype, but no associations were
      observed for rs1002076. Women who carried both rs17401966 AG/GG and rs1002076
      AG/AA genotypes of KIF1B had a 0.82-fold decreased risk (adjusted 95 % CI = 0.69
      0.97), compared with others. Additionally, there was no evidence of possible
      interactions between about-mentioned co-variants. Further genotype-phenotype
      correlation analysis indicated that the number of rs17401966 variant G allele was
      significantly associated with KIF1B mRNA expression levels (P for GLM = 0.003 and
      0.001 in all and Chinese subjects, respectively), with GG carriers having the
      lowest level of KIF1B mRNA expression. Taken together, the rs17401966
      polymorphism likely regulates KIF1B mRNA expression and thus may be associated
      with EOC risk in Eastern Chinese women. Larger, independent studies are warranted
      to validate our findings.

PMID- 25854173
TI  - MicroRNA-144 inhibits the proliferation, apoptosis, invasion, and migration of
      osteosarcoma cell line F5M2.
AB  - This study is aimed to investigate the role of microRNA-144 (miR-144) in
      osteosarcoma cell line F5M2 proliferation, apoptosis, invasion, and metastasis.
      Between 2007 and 2014, 66 cases of osteosarcoma samples in the corresponding
      adjacent normal tissue samples were selected from surgical resection or biopsy in
      the Department of Orthopedics, Shengjing Hospital, China Medical University. MiR
      144 levels and Ezrin messenger RNA (mRNA) levels in osteosarcoma and the adjacent
      bone tissues were detected, and clinical and pathological features were analyzed.
      Exogenous miR-144 was transfected into human osteosarcoma cell lines at two
      different concentrations (low and high), and the expression levels of miR-144 and
      Ezrin protein between highly metastatic osteosarcoma cells and lowly metastatic
      osteosarcoma cells were compared. Real-time polymerase chain reaction (RT-PCR)
      and Western blot were used for detecting the expression levels of miR-144 or
      Ezrin protein, respectively. Cell proliferation was measured by methylthiazol
      tetrazolium (MTT) assay. Cell invasion and migration was evaluated by Transwell
      assays. Finally, flow cytometry was employed to determine the cell apoptosis. MiR
      144 expression in osteosarcoma tissue was significantly lower than that in the
      surrounding normal bone tissue (P < 0.001), while Ezrin mRNA expression in
      osteosarcoma tissue was significantly higher than that in the surrounding normal
      bone tissue (P < 0.001); correlation analysis showed a significant negative
      correlation between miR-144 and Ezrin mRNA levels (r = 0.982, P < 0.001). MiR-144
      and Ezrin mRNA expressions were significantly related with cell metastasis (P <
      0.05) but were not related with other clinical factors such as gender, age, tumor
      location, tumor size, Enneking staging, and Dahlin's histological classification.
      The results of RT-PCR showed that the expression level of miR-144 in osteosarcoma
      cells increased after transfected with exogenous miR-144 mimics, and this
      increase positively correlated with the transfection concentration of miR-144
      mimics. Furthermore, Western blotting revealed a significant and dose-dependent
      decrease in Ezrin protein levels in F5M2 cells transfected with miR-144. MTT and
      Transwell assays showed that the invasion and metastasis of F5M2 cells was
      significantly decreased following exogenous overexpression of miR-144. Our study
      supports the view that the miR-144 may regulate Ezrin protein expression by
      inhibiting the invasion and metastasis of osteosarcoma cells.

PMID- 25854174
TI  - Gender and plasma iron biomarkers, but not HFE gene mutations, increase the risk
      of colorectal cancer and polyps.
AB  - A cohort study of patients included in the Basque Country colorectal cancer (CRC)
      screening programme was carried out to assess the risk of adenomatous polyps and
      CRC (P-CRC) associated with HFE gene mutations, with gender and with iron
      biomarkers (serum ferritin (SF), iron (Fe) and transferrin saturation index
      (TSI)). Among 432 included patients (mean age 59.8 years), 263 were men (60.9 %)
      and 169 women (39.1 %). P-CRC were identified in 221 patients (51.2 %) and no
      polyps (NP) in 211 patients (48.8 %). HFE mutations were identified in 43.8 % of
      the patients. C282Y/wt genotypic frequency was 6.8 % in the P-CRC group and 1.4 %
      in the NP group (p < 0.05). The allelic frequency was 3.8 versus 1.2 % (p <
      0.05). For laboratory, all three iron biomarkers showed a statistically
      significant difference: mean Fe, 91.29 +/- 34 for P-CRC and 80.81 +/- 30.59 for
      NP group. Mean TSI for P-CRC was 24.95 +/- 8.90 and 22.74 +/- 8.79 for NP group.
      Mean SF 308.09 +/- 536.32 for P-CRC and 177.55 +/- 159.95 for NP group. In a
      multivariate logistic regression analysis, only male gender (odds ratio (OR) =
      2.04, 1.29-3.22), SF (OR = 1.001, 1.0004-1.003) and Fe (OR = 1.01, 1.004-1.02)
      were related with the presence of CRC and adenoma. Men gender and raised serum
      iron biomarkers increase the risk of P-CRC.

PMID- 25854175
TI  - MicroRNA-199a-3p suppresses glioma cell proliferation by regulating the AKT/mTOR
      signaling pathway.
AB  - Glioma has been investigated for decades, but the prognosis remains poor because
      of rapid proliferation, its aggressive potential, and its resistance to
      chemotherapy or radiotherapy. The mammalian target of rapamycin (mTOR) is highly
      expressed and regulates cellular proliferation and cell growth. MicroRNAs
      (miRNAs) are small non-coding RNAs that regulate gene transcription and
      translation via up-regulating or down-regulating the levels of miRNAs. This study
      was conducted to explore the molecular functions of miR-199a-3p in glioma. We
      detected the expression of miR-199a-3p in glioma samples by quantitative PCR
      (qPCR). Then, we transfected the U87 and U251 cell lines with miR-199a-3p.
      Cellular proliferation, invasion, and apoptosis were assessed to explain the
      function of miR-199a-3p. PCR confirmed that the expression of miR-199a-3p was
      lower in glioma samples combined with normal brain tissues. The over-expression
      of miR-199a-3p might target mTOR and restrained cellular growth and proliferation
      but not invasive and apoptosis capability. Results indicated that cellular
      proliferation was inhibited to regulate the AKT/mTOR signaling pathway by
      elevating levels of miR-199a-3p. MiR-199a-3p in glioma cell lines has effects
      similar to the tumor suppressor gene on cellular proliferation via the AKT/mTOR
      signaling pathway.

PMID- 25854176
TI  - Bone Marrow Mesenchymal Stem Cells Alleviate Extracellular Kynurenine Levels, as
      Detected by High-Performance Liquid Chromatography.
AB  - Endothelial cell dysfunction plays an important role in the occurrence and
      development of sepsis, which is a consequence of the interaction between
      coagulation and inflammation. Kynurenine (KYN) is an endothelium-derived relaxing
      factor that makes a large contribution to sepsis pathophysiology. In this study,
      we investigated the influence of bone marrow mesenchymal stem cells (BMSCs) on
      KYN production by cultured endothelial cells. KYN and tryptophan (TRP)
      concentrations in cell supernatants were simultaneously measured with a high
      performance liquid chromatography (HPLC) system equipped with a fluorescence
      detector (FLD) and an ultraviolet detector (UVD). Our results revealed that
      lipopolysaccharide-stimulated endothelial cells produced more KYN, which was
      accompanied by a parallel decrease in TRP. When co-cultured with BMSCs, KYN and
      TRP production were significantly decreased compared to lipopolysaccharide (LPS)
      induction alone. Our results suggest that BMSCs can attenuate endothelial cell
      damage by decreasing KYN as detected with HPLC. This method is the first to be
      capable of capturing functional changes in the cells and is simple, fast, and
      suitable for cellular level research purposes. 

PMID- 25854177
TI  - Co-treatment with the non-steroidal anti-androgen drug, flutamide and the natural
      estrogen, 17beta-estradiol does not lead to additive reproductive impairment in
      juvenile Murray rainbowfish (Melanotaenia fluviatilis).
AB  - The aim of this study was to investigate if the anti-androgen, flutamide, and the
      estrogen, 17beta-estradiol work together to feminize juvenile Murray rainbowfish
      (Melanotaenia fluviatilis). Fish (60 days post-hatch) were exposed to 25 ng/L
      17beta-estradiol (E2), 25 ug/L flutamide (Flu low), 250 ug/L flutamide (Flu
      high), E2 + Flu low and E2 + Flu high. After 35 days of exposure, concentrations
      of sex steroid hormones, 17beta-estradiol and 11-keto testosterone (11-KT), were
      determined in the head; and vitellogenin (VTG) concentration was measured in the
      tail. The abdomens were used for histological investigation of the gonads.
      Treatment with E2 + Flu high resulted in reduction in body weights and lengths in
      males and condition factor in females. Intersex was noted in Flu high and E2 +
      Flu high treatments. Exposures to E2 and/or Flu (low and high) resulted in
      precocious oocyte development but inhibited sperm development. The 17beta
      estradiol levels decreased significantly in the heads of both sexes after
      exposures to E2 and/or Flu (high and low). Flu high and E2 alone increased the 11
      KT levels in both sexes. However, E2 + Flu low decreased 11-KT levels in males
      and increased them in females. Flutamide (low and high) induced VTG protein in
      the tails of both sexes. In males, VTG was not induced in the tail after exposure
      to E2. No significant effect of flutamide on E2-induced VTG concentration was
      noted. We conclude that co-treatment with flutamide and 17beta-estradiol does not
      lead to additive reproductive impairment in juvenile Murray rainbowfish.

PMID- 25854178
TI  - The physiologic anticoagulant and anti-inflammatory role of heparins and their
      utility in the prevention of pregnancy complications.
AB  - Accumulating evidence supports the concept of increased thrombin generation,
      placental vascular lesions, and inflammation as crucial points in the development
      of the great obstetrical syndromes [preeclampsia, intrauterine growth restriction
      (IUGR), preterm labor (PTL), preterm prelabor rupture of membranes (PROM), fetal
      demise and recurrent abortions]. In light of this, the role of heparins for
      primary or secondary prevention of these syndromes is becoming more and more
      apparent, mainly due to the antithrombotic and anti-inflammatory effects of
      heparins. There is agreement regarding the use of heparin in the prevention of
      gestational complications in patients with antiphospholipid syndrome, while its
      use for other obstetrical complications is under debate. In the present review we
      will describe the physiologic role of heparins on coagulation and inflammation
      and we will discuss current evidence regarding the use of heparins for the
      prevention/treatment of obstetrical syndromes. 

PMID- 25854179
TI  - Clinical applications of dual-channel transmit MRI: A review.
AB  - This article reviews the principle of dual-channel transmit MRI and highlights
      current clinical applications which are performed primarily at 3 Tesla. The main
      benefits of dual-channel transmit compared with single-transmit systems are the
      increased image contrast homogeneity and the decreased scanning time due to the
      more accurate local specific absorption ratio estimation, meaning that less
      conservative safety limits are needed. The dual-transmit approach has been
      particularly beneficial in body imaging applications, and is also promising in
      terms of cardiac, spine, and fetal imaging. Future advances in transmit SENSE,
      the combination of dual-channel transmit with high permittivity pads, as well as
      the potential increase in the number of transmit channels are also discussed.

PMID- 25854180
TI  - Retrieval of publications addressing shared decision making: an evaluation of
      full-text searches on medical journal websites.
AB  - BACKGROUND: Full-text searches of articles increase the recall, defined by the
      proportion of relevant publications that are retrieved. However, this method is
      rarely used in medical research due to resource constraints. For the purpose of a
      systematic review of publications addressing shared decision making, a full-text
      search method was required to retrieve publications where shared decision making
      does not appear in the title or abstract. OBJECTIVE: The objective of our study
      was to assess the efficiency and reliability of full-text searches in major
      medical journals for identifying shared decision making publications. METHODS: A
      full-text search was performed on the websites of 15 high-impact journals in
      general internal medicine to look up publications of any type from 1996-2011
      containing the phrase "shared decision making". The search method was compared
      with a PubMed search of titles and abstracts only. The full-text search was
      further validated by requesting all publications from the same time period from
      the individual journal publishers and searching through the collected dataset.
      RESULTS: The full-text search for "shared decision making" on journal websites
      identified 1286 publications in 15 journals compared to 119 through the PubMed
      search. The search within the publisher-provided publications of 6 journals
      identified 613 publications compared to 646 with the full-text search on the
      respective journal websites. The concordance rate was 94.3% between both full
      text searches. CONCLUSIONS: Full-text searching on medical journal websites is an
      efficient and reliable way to identify relevant articles in the field of shared
      decision making for review or other purposes. It may be more widely used in
      biomedical research in other fields in the future, with the collaboration of
      publishers and journals toward open-access data.

PMID- 25854181
TI  - Beyond the thale: comparative genomics and genetics of Arabidopsis relatives.
AB  - For decades a small number of model species have rightly occupied a privileged
      position in laboratory experiments, but it is becoming increasingly clear that
      our knowledge of biology is greatly improved when informed by a broader diversity
      of species and evolutionary context. Arabidopsis thaliana has been the primary
      model organism for plants, benefiting from a high-quality reference genome
      sequence and resources for reverse genetics. However, recent studies have made a
      group of species also in the Brassicaceae family and closely related to A.
      thaliana a focal point for comparative molecular, genomic, phenotypic and
      evolutionary studies. In this Review, we emphasize how such studies complement
      continued study of the model plant itself, provide an evolutionary perspective
      and summarize our current understanding of genetic and phenotypic diversity in
      plants. 

PMID- 25854183
TI  - Genetic testing. ACMG guides on the interpretation of sequence variants.

PMID- 25854184
TI  - RNA. Detailed probing of RNA structure in vivo.

PMID- 25854182
TI  - High-throughput functional genomics using CRISPR-Cas9.
AB  - Forward genetic screens are powerful tools for the discovery and functional
      annotation of genetic elements. Recently, the RNA-guided CRISPR (clustered
      regularly interspaced short palindromic repeat)-associated Cas9 nuclease has been
      combined with genome-scale guide RNA libraries for unbiased, phenotypic
      screening. In this Review, we describe recent advances using Cas9 for genome
      scale screens, including knockout approaches that inactivate genomic loci and
      strategies that modulate transcriptional activity. We discuss practical aspects
      of screen design, provide comparisons with RNA interference (RNAi) screening, and
      outline future applications and challenges. 

PMID- 25854185
TI  - Effect of Diabetes Mellitus on Adipocyte-Derived Stem Cells in Rat.
AB  - Diabetes mellitus affects the adipose tissue and mesenchymal stem cells derived
      from the adipose stroma and other tissues. Previous reports suggest that bone
      morphogenetic protein 4 (BMP4) is involved in diabetic complications, at the same
      time playing an important role in the maintenance of stem cells. In this study,
      we used rats transgenic for human islet amyloid polypeptide (HIP rats), a model
      of type 2 diabetes, to study the effect of diabetes on adipocyte-derived stem
      cells, referred to as dedifferentiated fat (DFAT) cells. Our results show that
      BMP4 expression in inguinal adipose tissue is significantly increased in HIP rats
      compared to controls, whereas matrix Gla protein (MGP), an inhibitor of BMP4 is
      decreased as determined by quantitative PCR, and immunofluorescence. In addition,
      adipose vascularity and expression of multiple endothelial cell markers was
      increased in the diabetic tissue, visualized by immunofluorescence for
      endothelial markers. The endothelial markers co-localized with the enhanced BMP4
      expression, suggesting that vascular cells play a role BMP4 induction. The DFAT
      cells are multipotent stem cells derived from white mature adipocytes that
      undergo endothelial and adipogenic differentiation. DFAT cells prepared from the
      inguinal adipose tissue in HIP rats exhibited enhanced proliferative capacity
      compared to wild type. In addition, their ability to undergo both endothelial
      cell and adipogenic lineage differentiation was enhanced, as well as their
      response to BMP4, as assessed by lineage marker expression. We conclude that the
      DFAT cells are affected by diabetic changes and may contribute to the adipose
      dysfunction in diabetes.

PMID- 25854187
TI  - [Kinematic alignment in total knee arthroplasty : Concept, evidence base and
      limitations].
AB  - BACKGROUND: Against the background that 20 % of patients are dissatisfied after
      total knee arthroplasty, there is ongoing controversy about optimal alignment. In
      this context, orientating the prosthetic components to the natural kinematic axes
      of the knee appears to be an interesting new concept. METHODS: The objective of
      this paper is to provide a critical review of the current literature and our own
      research data regarding the concept of kinematically aligned total knee
      arthroplasty with the current evidence base and potential limitations. RESULTS
      AND DISCUSSION: In the recent literature faster rehabilitation, better knee
      function, and higher patient satisfaction are described compared to conventional
      alignment, even if the postoperative alignment deviates more than 3 degrees  from
      the mechanical axis. However, the technique may not be suitable for every patient
      and pathology, and further research is necessary to set the correct indication.

PMID- 25854186
TI  - Oxidative stress in fungi: its function in signal transduction, interaction with
      plant hosts, and lignocellulose degradation.
AB  - In this review article, we want to present an overview of oxidative stress in
      fungal cells in relation to signal transduction, interaction of fungi with plant
      hosts, and lignocellulose degradation. We will discuss external oxidative stress
      which may occur through the interaction with other microorganisms or plant hosts
      as well as internally generated oxidative stress, which can for instance
      originate from NADPH oxidases or "leaky" mitochondria and may be modulated by the
      peroxiredoxin system or by protein disulfide isomerases thus contributing to
      redox signaling. Analyzing redox signaling in fungi with the tools of molecular
      genetics is presently only in its beginning. However, it is already clear that
      redox signaling in fungal cells often is linked to cell differentiation (like the
      formation of perithecia), virulence (in plant pathogens), hyphal growth and the
      successful passage through the stationary phase. 

PMID- 25854188
TI  - [Objectifying results in total knee arthroplasty: Is "patient satisfaction"
      adequate].
AB  - BACKGROUND: Arthroplasty is an effective treatment for end-stage osteoarthritis
      of the knee and is one of Germany's most frequently performed orthopedic
      procedures. DISCUSSION: However, a considerable number of patient are not
      satisfied with the results after knee arthroplasty. The patient's perspective is
      particularly important for shared decision making. "Patient satisfaction" with
      the surgery is an expression of the patient's perspective, but might not be
      sufficient as the only outcome measure. There is no international consensus which
      outcome measures should be used after knee arthroplasty. CONCLUSION: Therefore,
      different measurement tools are used for the acquisition of a variety of outcome
      measures in order to quantify the results of knee arthroplasty. These tools
      should be used according to their reliability, validity, and responsiveness. This
      article provides an overview about available measurement tools.

PMID- 25854190
TI  - [Update Orthopedics - endoprosthesis].

PMID- 25854189
TI  - [Total knee arthroplasty in 2014 : Results, expectations, and complications].
AB  - BACKGROUND: Aseptic loosening seems to have become a minor problem in total knee
      arthroplasty. In contrast to that, new challenges are defined by changing
      patients' expectations. Beside reduction of pain and improving mobility, modern
      implants should not be noticed as such and should not limit sports activities.
      OBJECTIVES: In this paper, a summary of the development and the current situation
      of total knee arthroplasty (e.g., implantation numbers, hospitality, operation
      time, and infection rates) are provided. The data are compared in an
      international context. In addition, current trends and developments from recent
      years are shown and rated according to the literature. MATERIALS AND METHODS: The
      paper is based on a literature search (PubMed) and analyses of published official
      statistical data and expert recommendations. RESULTS: Implantation numbers have
      been declining gradually in Germany since 2009. In 2013, 127,077 total knee
      arthroplasties were implanted. In contrast, the number of revision operations has
      increased gradually during the last decade. In addition, hospital stay and
      operation time have declined. CONCLUSION: The development of implants,
      instruments, and operation techniques results from changing patients'
      expectations. All innovations must be compared against the results of well-proven
      techniques. The arthroplasty register may be an instrument to evaluate the
      results of new techniques and implants in a broad clinical application in terms
      of survival.

PMID- 25854191
TI  - Clinical curative effect of Mesalt combined with Mepilex dressing in
      postoperative infection of inguinal hernia.
AB  - BACKGROUND: Inguinal hernia is a common surgical disease. Tension-free
      hernioplasty is currently commonly used for its treatment, with multiple
      advantages such as simple surgical method, low recurrence rate, and ability to be
      performed in primary care hospitals, but the risk of incision infection still
      exists. Mild infection can be cured by local washing, dressing, and systemic
      antibiotics. If the infection is severe, the wound may not heal after removing
      the patch, and secondary suturing is needed. MATERIAL AND METHODS: A total of 60
      patients with postoperative infection after tension-free repair of inguinal
      hernia were randomly divided into control (n=30) and treatment (n=30) groups.
      Patients in the treatment group received Mesalt combined with Mepilex for
      dressing while the patients in the control group received conventional gauze for
      dressing. Pain degree, wound healing time, and dressing times were observed.
      RESULTS: The clinical therapeutic effect in the treatment group was significantly
      better than in the control group. The treatment group exhibited significantly
      less pain when patients receive dressing, shorter wounds healing time (15 +/- 3.5
      vs. 30 +/- 5.0), and less dressing frequency (10 +/- 2.1 vs. 20 +/- 2.4).
      CONCLUSIONS: Mesalt combined with Mepilex can effectively improve postoperative
      infection after inguinal hernia treatment, obviously reducing pain, shorting
      wound healing time, and decreasing dressing frequency. It can be widely used in
      clinical practice.

PMID- 25854192
TI  - Crater/ulcerated form of infundibular squamous cell carcinoma: A possible
      distinct entity as a malignant (or high-grade) counterpart to keratoacanthoma.
AB  - Follicular squamous cell carcinoma (SCC) with infundibular differentiation
      includes the common and crater forms of infundibular SCC. We previously
      considered the crater/ulcerated infundibular SCC to be a progressive condition of
      the common form and histopathologically studied an additional five cases of the
      crater/ulcerated infundibular SCC, the results of which suggested the following
      characteristic histopathological features and possible developmental process in
      this type of SCC: (i) a considerable number of continuous hyperplastic follicular
      infundibula, which may develop at the beginning of the disease; (ii) hyperplastic
      infundibula exhibiting an abrupt or gradual transition to the SCC component,
      which frequently change relative to the neoplastic infundibular canal; and (iii)
      the presence of multiple sites of branching of the neoplastic infundibular canals
      and/or complete involvement of large cysts in the neoplastic process over the
      center of the lesion, resulting in ulceration. Based on these histopathological
      findings, we considered that crater/ulcerated infundibular SCC involve a
      considerable number of continuous follicular infundibula from the start, although
      some cases may develop from the common form. We also emphasize the possible
      aggressive biological behavior of the crater/ulcerated form. Keratoacanthoma (KA)
      is a unique, benign or borderline malignant neoplasm exhibiting follicular
      (infundibular/isthmic) differentiation characterized by the involvement of
      continuous follicular infundibula in multiples. From this standpoint, we consider
      that crater/ulcerated infundibular SCC is possibly related to KA in terms of
      histogenesis and is a malignant (or high-grade) counterpart of KA. 

PMID- 25854193
TI  - Evaluating aquatic invertebrate vulnerability to insecticides based on intrinsic
      sensitivity, biological traits, and toxic mode of action.
AB  - In the present study, the authors evaluated the vulnerability of aquatic
      invertebrates to insecticides based on their intrinsic sensitivity and their
      population-level recovery potential. The relative sensitivity of invertebrates to
      5 different classes of insecticides was calculated at the genus, family, and
      order levels using the acute toxicity data available in the US Environmental
      Protection Agency ECOTOX database. Biological trait information was linked to the
      calculated relative sensitivity to evaluate correlations between traits and
      sensitivity and to calculate a vulnerability index, which combines intrinsic
      sensitivity and traits describing the recovery potential of populations partially
      exposed to insecticides (e.g., voltinism, flying strength, occurrence in drift).
      The analysis shows that the relative sensitivity of arthropods depends on the
      insecticide mode of action. Traits such as degree of sclerotization, size, and
      respiration type showed good correlation to sensitivity and can be used to make
      predictions for invertebrate taxa without a priori sensitivity knowledge. The
      vulnerability analysis revealed that some of the Ephemeroptera, Plecoptera, and
      Trichoptera taxa were vulnerable to all insecticide classes and indicated that
      particular gastropod and bivalve species were potentially vulnerable.
      Microcrustaceans (e.g., daphnids, copepods) showed low potential vulnerability,
      particularly in lentic ecosystems. The methods described in the present study can
      be used for the selection of focal species to be included as part of ecological
      scenarios and higher tier risk assessments.

PMID- 25854194
TI  - Preparation, structure, and versatile reactivity of pseudocyclic benziodoxole
      triflate, new hypervalent iodine reagent.
AB  - A new pseudocyclic triflate derivative of benziodoxole (IBA-OTf) was prepared and
      characterized by X-ray analysis. This highly electrophilic reagent readily reacts
      with various organic substrates to give the corresponding products in good
      yields. Furthermore, IBA-OTf can be used as a catalyst with m-chloroperoxybenzoic
      acid as the terminal oxidant. 

PMID- 25854195
TI  - Trends in nontuberculous mycobacterial disease in hospitalized subjects in Spain
      (1997-2010) according to HIV infection.
AB  - OBJECTIVES: The aim of the study was to estimate the incidence of nontuberculous
      mycobacterial (NTM) disease and the rate of NTM disease-related mortality and to
      analyse trends in these variables according to HIV infection. METHODS: We
      performed a retrospective study for the period 1997-2010 using data from the
      Minimum Basic Data Set (MBDS) provided by the Spanish Ministry of Health. The
      exposure variables were: (i) HIV infection (HIV positive versus HIV negative);
      (ii) calendar period in relation to widespread use of combination antiretroviral
      therapy (cART) [1997-1999 (early cART period), 2000-2003 (middle cART period) and
      2004-2010 (late cART period)]. The outcome variables were (i) new NTM disease
      diagnosis and (ii) mortality. RESULTS: A total of 3729 cases of incident NTM
      disease were collected in MBDS, 1795 in the HIV-negative group and 1934 in the
      HIV-positive group, among whom 602 deaths occurred, 223 in the HIV-negative group
      and 379 in the HIV-positive group. The incidence of NTM disease and the rate of
      NTM disease-related mortality were 1000-fold higher in the HIV-positive group
      than in the HIV-negative group. Regarding the incidence of NTM disease, in the
      HIV-negative group the incidence increased from 2.91 to 3.97 events per 1,000,000
      patient-years from 1997-1999 to 2004-2010 (P < 0.001), while in the HIV-positive
      group the incidence decreased from 2.29 to 0.71 events per 1000 patient-years
      from 1997-1999 to 2004-2010 (P < 0.001). Regarding mortality, in the HIV-negative
      group mortality increased from 2.63 to 4.26 events per 10,000,000 patient-years
      from 1997-1999 to 2000-2003 (P = 0.059), and then the rate stabilized at around
      3.87 events per 10,000,000 patient-years in 2004-2010 (P = 0.128), while in the
      HIV-positive group mortality decreased from 4.28 to 1.39 events per 10,000
      patient-years from 1997-1999 to 2004-2010 (P < 0.001). CONCLUSIONS: HIV infection
      was associated with a higher NTM disease incidence and higher NTM disease-related
      mortality than in the general population, but these rates decreased in the HIV
      positive group from 1997-1999 to 2004-2010, whereas the NTM disease incidence
      increased in the HIV-negative group.

PMID- 25854196
TI  - Diabetes treatment-related quality of life is associated with levels of self-care
      activities in insulin injection among Japanese patients with type 2 diabetes:
      Diabetes Distress and Care Registry at Tenri (DDCRT 8).
AB  - AIMS: We investigated the association between diabetes treatment-related quality
      of life (QOL) and levels of self-care activities in insulin injection among
      Japanese patients with type 2 diabetes. METHODS: Data from 1394 patients with
      type 2 diabetes on insulin therapy were obtained from a diabetes registry in
      Japan. We used the Diabetes Therapy-Related QOL (DTR-QOL) questionnaire and
      relative risk regression analysis to assess the independent association of high
      levels of self-care activities in insulin injection and DTR-QOL scores while
      adjusting for possible confounders. RESULTS: The mean age, BMI and HbA1c level
      were 65.8 years, 24.8 kg/m(2) and 62 mmol/mol (7.8 %), respectively. The
      frequency of insulin injection omission was associated with DTR-QOL scores. In
      the multivariable-adjusted model, the relative risks for high levels of self-care
      activities in insulin injection was 1.15 (95 % confidence interval, 1.05-1.26) in
      the highest quintile compared with those in the lowest quintile of DTR-QOL
      scores. Subgroup analysis confirmed this association in patients <65 years.
      CONCLUSIONS: DTR-QOL was associated with self-reported levels of self-care
      activities in insulin injection, particularly among Japanese patients <65 years
      with type 2 diabetes. DTR-QOL might be a useful tool to identify patients who
      consequently omit insulin. For patients with low DTR-QOL score, healthcare
      providers should discuss their treatment-related problems to prevent insulin
      injection omission.

PMID- 25854197
TI  - Magnetic/NIR-responsive drug carrier, multicolor cell imaging, and enhanced
      photothermal therapy of gold capped magnetite-fluorescent carbon hybrid
      nanoparticles.
AB  - This paper reports a type of multifunctional hybrid nanoparticle (NP) composed of
      gold nanocrystals coated on and/or embedded in a magnetite-fluorescent porous
      carbon core-shell NP template (Fe3O4@PC-CDs-Au) for biomedical applications,
      including magnetic/NIR-responsive drug release, multicolor cell imaging, and
      enhanced photothermal therapy. The synthesis of the Fe3O4@PC-CDs-Au NPs firstly
      involves the preparation of core-shell template NPs with magnetite nanocrystals
      clustered in the cores and fluorescent carbon dots (CDs) embedded in a porous
      carbon shell, followed by an in situ reduction of silver ions (Ag(+)) loaded in
      the porous carbon shell and a subsequent replacement of Ag NPs with Au NPs
      through a galvanic replacement reaction using HAuCl4 as a precursor. The Fe3O4@PC
      CDs-Au NPs can enter the intracellular region and light up mouse melanoma B16F10
      cells in multicolor mode. The porous carbon shell, anchored with hydrophilic
      hydroxyl/carboxyl groups, endows the Fe3O4@PC-CDs-Au NPs with excellent stability
      in the aqueous phase and a high loading capacity (719 mg g(-1)) for the anti
      cancer drug doxorubicin (DOX). The superparamagnetic Fe3O4@PC-CDs-Au NPs with a
      saturation magnetization of 23.26 emu g(-1) produce localized heat under an
      alternating magnetic field, which triggers the release of the loaded drug. The
      combined photothermal effects of the Au nanocrystals and the CDs on/in the carbon
      shell can not only regulate the release rate of the loaded drug, but also
      efficiently kill tumor cells under NIR irradiation. Benefitting from their
      excellent optical properties, their magnetic field and NIR light-responsive drug
      release capabilities and their enhanced photothermal effect, such nanostructured
      Fe3O4@PC-CDs-Au hybrid NPs are very promising for simultaneous imaging
      diagnostics and high efficacy therapy. 

PMID- 25854198
TI  - Photoswitchable membranes based on peptide-modified nanoporous anodic alumina:
      toward smart membranes for on-demand molecular transport.
AB  - A smart and reversibly photoswitchable membrane based on an azobenzene photo
      switch containing peptides attached inside the pores of nanoporous anodic alumina
      membranes (NAAMs) is presented. The transport of molecules of interest across the
      photoswitchable peptide (PSP) functionalized NAAMs can be effectively controlled
      and manipulated as a function of the photostationary state of the azobenzene
      group in a PSP. 

PMID- 25854199
TI  - Transcription of 4'-thioDNA templates to natural RNA in vitro and in mammalian
      cells.
AB  - Synthetic chemically modified nucleic acids, which are compatible with DNA/RNA
      polymerases, have great potential as a genetic material for synthetic biological
      studies. A comprehensive analysis of the transcription of 4'-thioDNA templates to
      natural RNA is herein reported. The modifications of DNA with 2'-deoxy-4'
      thionucleosides, so-called 4'-thioDNA, were found to act as templates for
      transcription with RNA polymerases both in vitro and in mammalian cells. 

PMID- 25854200
TI  - The reactivity of stoichiometric tungsten oxide clusters towards carbon monoxide:
      the effects of cluster sizes and charge states.
AB  - Density functional theory (DFT) calculations are employed to investigate the
      reactivity of tungsten oxide clusters towards carbon monoxide. Extensive
      structural searches show that all the ground-state structures of (WO3)n(+) (n = 1
      4) contain an oxygen radical center with a lengthened W-O bond which is highly
      active in the oxidation of carbon monoxide. Energy profiles are calculated to
      determine the reaction mechanisms and evaluate the effect of cluster sizes. The
      monomer WO3(+) has the highest reactivity among the stoichiometric clusters of
      different sizes (WO3)n(+) (n = 1-4). The reaction mechanisms for CO with mono
      nuclear stoichiometric tungsten oxide clusters with different charges (WO3(
      /0/+)) are also studied to clarify the influence of charge states. Our calculated
      results show that the ability to oxidize CO gets weaker from WO3(+) to WO3(-) as
      the negative charge accumulates progressively. 

PMID- 25854202
TI  - Kinetic study on removal of heavy metal ions from aqueous solution by using soil.
AB  - In the present study, the feasibility of soil used as a low-cost adsorbent for
      the removal of Cu(2+), Zn(2+), and Pb(2+) ions from aqueous solution was
      investigated. The kinetics for adsorption of the heavy metal ions from aqueous
      solution by soil was examined under batch mode. The influence of the contact time
      and initial concentration for the adsorption process at pH of 4.5, under a
      constant room temperature of 25 +/- 1  degrees C were studied. The adsorption
      capacity of the three heavy metal ions from aqueous solution was decreased in
      order of Pb(2+) > Cu(2+) > Zn(2+). The soil was characterized by Fourier
      transform infrared (FTIR) spectroscopy, scanning electron microscopic-energy
      dispersive X-ray (SEM-EDX), and Brunauer, Emmett, and Teller (BET) surface area
      analyzer. From the FTIR analysis, the experimental data was corresponded to the
      peak changes of the spectra obtained before and after adsorption process. Studies
      on SEM-EDX showed distinct adsorption of the heavy metal ions and the mineral
      composition in the study areas were determined to be silica (SiO2), alumina
      (Al2O3), and iron(III) oxide (FeO3). A distinct decrease of the specific surface
      area and total pore volumes of the soil after adsorption was found from the BET
      analysis. The experimental results obtained were analyzed using four adsorption
      kinetic models, namely pseudo-first-order, pseudo-second-order, Elovich, and
      intraparticle diffusion. Evaluating the linear correlation coefficients, the
      kinetic studies showed that pseudo-second-order equation described the data
      appropriable than others. It was concluded that soil can be used as an effective
      adsorbent for removing Cu(2+), Zn(2+), and Pb(2+) ions from aqueous solution. 

PMID- 25854201
TI  - Perfluoroalkyl and polyfluoroalkyl substances in consumer products.
AB  - Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are used in a wide range of
      products of all day life. Due to their toxicological potential, an emerging focus
      is directed towards their exposure to humans. This study investigated the PFAS
      load of consumer products in a broad perspective. Perfluoroalkyl sulfonic acids
      (C4, C6-C8, C10-PFSA), carboxylic acids (C4-C14-PFCA) and fluorotelomer alcohols
      (4:2, 6:2; 8:2 and 10:2 FTOH) were analysed in 115 random samples of consumer
      products including textiles (outdoor materials), carpets, cleaning and
      impregnating agents, leather samples, baking and sandwich papers, paper baking
      forms and ski waxes. PFCA and PFSA were analysed by HPLC-MS/MS, whereas FTOH were
      detected by GC/CI-MS. Consumer products such as cleaning agents or some baking
      and sandwich papers show low or negligible PFSA and PFCA contents. On the other
      hand, high PFAS levels were identified in ski waxes (up to about 2000 MUg/kg
      PFOA), leather samples (up to about 200 MUg/kg PFBA and 120 MUg/kg PFBS), outdoor
      textiles (up to 19 MUg/m(2) PFOA) and some other baking papers (up to 15 MUg/m(2)
      PFOA). Moreover, some test samples like carpet and leather samples and outdoor
      materials exceeded the EU regulatory threshold value for PFOS (1 MUg/m(2)). A
      diverse mixture of PFASs can be found in consumer products for all fields of
      daily use in varying concentrations. This study proves the importance of
      screening and monitoring of consumer products for PFAS loads and the necessity
      for an action to regulate the use of PFASs, especially PFOA, in consumer
      products.

PMID- 25854203
TI  - Phytoremediation of salt-affected soils: a review of processes, applicability,
      and the impact of climate change.
AB  - Soil salinization affects 1-10 billion ha worldwide, threatening the agricultural
      production needed to feed the ever increasing world population. Phytoremediation
      may be a cost-effective option for the remediation of these soils. This review
      analyzes the viability of using phytoremediation for salt-affected soils and
      explores the remedial mechanisms involved. In addition, it specifically addresses
      the debate over plant indirect (via soil cation exchange enhancement) or direct
      (via uptake) role in salt remediation. Analysis of experimental data for
      electrical conductivity (ECe) + sodium adsorption ratio (SAR) reduction and plant
      salt uptake showed a similar removal efficiency between salt phytoremediation and
      other treatment options, with the added potential for phytoextraction under non
      leaching conditions. A focus is also given on recent studies that indicate
      potential pathways for increased salt phytoextraction, co-treatment with other
      contaminants, and phytoremediation applicability for salt flow control. Finally,
      this work also details the predicted effects of climate change on soil
      salinization and on treatment options. The synergetic effects of extreme climate
      events and salinization are a challenging obstacle for future phytoremediation
      applications, which will require additional and multi-disciplinary research
      efforts.

PMID- 25854204
TI  - Occurrence and behaviors of fluorescence EEM-PARAFAC components in drinking water
      and wastewater treatment systems and their applications: a review.
AB  - Fluorescence excitation emission matrices-parallel factor analysis (EEM-PARAFAC)
      is a powerful tool for characterizing dissolved organic matter (DOM), and it is
      applied in a rapidly growing number of studies on drinking water and wastewater
      treatments. This paper presents an overview of recent findings about the
      occurrence and behavior of PARAFAC components in drinking water and wastewater
      treatments, as well as their feasibility for assessing the treatment performance
      and water quality including disinfection by-product formation potentials (DBPs
      FPs). A variety of humic-like, protein-like, and unique (e.g., pyrene-like)
      fluorescent components have been identified, providing valuable insights into the
      chemical composition of DOM and the effects of various treatment processes in
      engineered systems. Coagulation/flocculation-clarification preferentially removes
      humic-like components, and additional treatments such as biological activated
      carbon filtration, anion exchange, and UV irradiation can further remove DOM from
      drinking water. In contrast, biological treatments are more effective for protein
      like components in wastewater treatments. PARAFAC components have been proven to
      be valuable as surrogates for conventional water quality parameter, to track the
      changes of organic matter quantity and quality in drinking water and wastewater
      treatments. They are also feasible for assessing formations of trihalomethanes
      and other DBPs and evaluating treatment system performance. Further studies of
      EEM-PARAFAC for assessing the effects of the raw water quality and variable
      treatment conditions on the removal of DOM, and the formation potentials of
      various emerging DBPs, are essential for optimizing the treatment processes to
      ensure treated water quality.

PMID- 25854205
TI  - Basin-scale emission and multimedia fate of triclosan in whole China.
AB  - This study aimed to investigate the emission and multimedia fate as well as
      potential risks of triclosan (TCS) in all of 58 basins in China. The results
      showed that the total usage of TCS in whole China was 100 t/year, and the
      discharge to the receiving environment was estimated to be 66.1 t/year. The
      predicted TCS concentrations by the level III fugacity model were within an order
      of magnitude of the reported measured concentrations. TCS (90.8%) was discharged
      into the water compartment and 9.2% to the soil compartment. The TCS
      concentration levels in east China were found generally higher than in west
      China. In addition, the input flux for TCS to seawater was largely attributed to
      the seasonal variations in advection flows. Preliminary risk assessment showed
      that medium to high ecological risks for TCS would be expected in the eastern
      part of China due to the high population density.

PMID- 25854206
TI  - The phytotoxicity of ionic liquids from natural pool of (-)-menthol with
      tetrafluoroborate anion.
AB  - Over the last several decades, ionic liquids have become a promising alternative
      to conventional organic solvents. Initially, ionic liquids were described as
      "environmentally friendly" substances. However, the results of numerous studies
      proved that the effects of these compounds on individual ecosystems might be
      adverse. The presented paper discusses the effect of ionic salts containing
      natural chiral substituent: (1R,2S,5R)-(-)-menthol in cation and a
      tetrafluoroborate anion of a general formula of [Cn-Im-Men][BF4] of
      implementation into the soil on the growth of spring barley and common radish in
      their early development stages. The obtained results showed that the greatest
      phytotoxicity was exhibited by ionic liquids containing substituents with the
      smallest possible number of carbon atoms. The further increase in the length of
      the chain did not increase the toxicity of these salts for terrestrial plants.
      Moreover, a compound with a substituent having a chain length of 11 carbon atoms
      was found to be non-toxic to common radish. The experiment under discussion
      showed also the effect of these tetrafluoroborates, used in the form of spray, on
      the development of common sorrel, gallant soldier and white goosefoot. The tests
      carried out also showed that the most toxic were the compounds with 1 and 3
      carbon atoms. The phytotoxicity of tetrafluoroborates was positively correlated
      with the concentration of these compounds in the soil and was dependent on the
      genetic features of the genres and varieties of plants used in the experiment. 

PMID- 25854207
TI  - Household pesticide exposure and the risk of childhood acute leukemia in
      Shanghai, China.
AB  - Childhood acute leukemia (AL) is the most common malignant tumor in children, but
      its etiology remains largely unknown. We investigated the relationship between
      household exposure to pesticides and childhood AL. Between 2009 and 2010 in
      Shanghai, a total of 248 newly diagnosed cases of AL and 111 gender-, age-, and
      hospital-matched controls were included. Five nonspecific dialkyl phosphate (DAP)
      metabolites of organophosphate pesticides (OPPs) [including dimethyl phosphate
      (DMP), diethyl phosphate (DEP), dimethyl thiophosphate (DMTP), diethyl
      thiophosphate (DETP), and diethyl dithiophosphate (DEDTP)] in the urine were
      analyzed by gas chromatography. The results showed that the median DMP, DEP,
      DMTP, DETP, and DEDEP levels adjusted for creatinine (Cr) in cases (13.2, 10.0,
      31.3, 8.5, and 6.1 MUg g(-1), respectively) were all significantly elevated
      compared with those in controls (3.6, 3.6, 13.3, 2.7, and 1.7 MUg g(-1),
      respectively) (P < 0.05). The household use of mosquito repellent was
      significantly associated with an increased risk of childhood AL (odds ratio (OR)
      = 1.9; 95% confidence interval (CI) 1.2-3.1). Moreover, higher exposures were
      significantly associated with an elevated risk of childhood AL for DMs, DEs, and
      DAPs. Our findings support the notion that the household use of pesticides may
      play a role in the etiology of childhood AL and provide some evidence to warrant
      further investigation of the link between household pesticide exposures and
      childhood AL in Shanghai.

PMID- 25854208
TI  - Effect of magnetic iron oxide (Fe3O4) nanoparticles on the growth and
      photosynthetic pigment content of Picochlorum sp.
AB  - Magnetite iron oxide (Fe3O4) nanoparticles (NPs) are key materials applied in
      many different fields of modern technology. The potential environmental impact of
      these NPs is of great concern. In this study, initially the effect of Fe3O4 NPs
      size (20 and 40 nm) as well as bulk (>100 nm) at 200 mg L(-1) on Picochlorum sp.
      (Trebouxiophyceae, Chlorophyta) is investigated during the different growth
      phases. The most inhibitory NPs were then chosen to assess their effects at
      different concentrations. The 20 nm NPs at 200 mg L(-1) were found to
      significantly reduce the viable cell concentration and chlorophyll a content
      during the exponential growth phase compared to the other particle sizes.
      However, the 20 nm NPs at different concentrations were found to promote algal
      growth during the late growth stages (stationary and decline phases) compared to
      the control. Additionally, algae were found to accelerate the aggregation and
      sedimentation of nanoparticles into the medium and therefore can be considered as
      potential organisms for bioremediation of nano-pollution.

PMID- 25854209
TI  - What factors drive the variations of phytoplankton, ciliate and mesozooplankton
      communities in the polluted southern coast of Sfax, Tunisia?
AB  - We studied the spatial distribution of phytoplankton, ciliate and mesozooplankton
      communities coupled with environmental factors in the southern coast of Sfax
      (central eastern coastline of Tunisia). Phytoplankton assemblages were dominated
      by Dinophyceae (69.99%) and Bacillariophyceae (15.88%). The ciliate community
      consisted of Spirotrichea with a dominance of Tintinnopsis beroidea (57.69%). The
      mesozooplankton community was dominated by copepods representing 66.12% of the
      total zooplankton. Oithona nana showed a high frequency mainly in stations 9 and
      10 with 66.86 and 64.65%, respectively. Some toxic phytoplankton species were
      recorded in the present study site. For this reason, the pollution generated in
      this area presents a slight degradation of the water quality and can be
      responsible for the bloom generated by the high proliferation of these toxic
      microalgae. The pollution generated by industrial activities has an effect on the
      spatial distribution of phytoplankton, ciliate and copepod communities with a
      reduction of their diversity indexes.

PMID- 25854210
TI  - Occurrence of cyanobacteria and microcystin toxins in raw and treated waters of
      the Nile River, Egypt: implication for water treatment and human health.
AB  - Monitoring of cyanobacteria and their associated toxins has intensified in raw
      water sources of drinking water treatment plants (WTPs) in most countries of the
      world. However, it is not explored yet for Egyptian WTPs. Therefore, this study
      was undertaken to investigate the occurrence of cyanobacteria and their
      microcystin (MC) toxins in the Nile River source water of Damietta WTP during
      warm months (April-September 2013) and to evaluate the removal efficiency of both
      cyanobacterial cells and MCs by conventional methods used in this plant as a
      representative of Egyptian drinking WTPs. The results showed that the source
      water at the intake of Damietta WTP contained dense cyanobacterial population
      (1.1-6.6 * 107 cells L(-1)) dominated by Microcystis aeruginosa. This bloom was
      found to produce MC-RR and MC-LR. Both cyanobacterial cell density and
      intracellular MCs in the intake source water increased with the increase in
      temperature and nutrients during the study period, with maximum values obtained
      in August. During treatment processes, cyanobacterial cells were incompletely
      removed by coagulation/flocculation/sedimentation (C/F/S; 91-96.8%) or sand
      filtration (93.3-98.9%). Coagulation/flocculation induced the release of MCs into
      the ambient water, and the toxins were not completely removed or degraded during
      further treatment stages (filtration and chlorination). MCs in outflow tank water
      were detected in high concentrations (1.1-3.6 MUg L - 1), exceeding WHO
      provisional guideline value of 1 MUg L - 1 for MC-LR in drinking water. Based on
      this study, regular monitoring of cyanobacteria and their cyanotoxins in the
      intake source water and at different stages at all WTPs is necessary to provide
      safe drinking water to consumers or to prevent exposure of consumers to hazardous
      cyanobacterial metabolites.

PMID- 25854211
TI  - The use of chlorate, nitrate, and perchlorate to promote crude oil mineralization
      in salt marsh sediments.
AB  - Due to the high volume of crude oil released by the Deepwater Horizon oil spill,
      the salt marshes along the gulf coast were contaminated with crude oil.
      Biodegradation of crude oil in salt marshes is primarily limited by oxygen
      availability due to the high organic carbon content of the soil, high flux rate
      of S(2-), and saturated conditions. Chlorate, nitrate, and perchlorate were
      evaluated for use as electron acceptors in comparison to oxygen by comparing oil
      transformation and mineralization in mesocosms consisting of oiled salt marsh
      sediment from an area impacted by the BP Horizon oil spill. Mineralization rates
      were determined by measuring CO2 production and delta (13)C of the produced CO2
      and compared to transformation evaluated by measuring the alkane/hopane ratios
      over a 4-month period. Total alkane/hopane ratios decreased (~55-70 %) for all
      treatments in the following relative order: aerated ~ chlorate > nitrate >
      perchlorate. Total CO2 produced was similar between treatments ranging from 550
      700 mg CO2-C. The delta (13)C-CO2 values generally ranged between the indigenous
      carbon and oil values (-17 and -270/00, respectively). Oil mineralization was
      greatest for the aerated treatments and least for the perchlorate amended. Our
      results indicate that chlorate has a similar potential as oxygen to support oil
      mineralization in contaminated salt marshes, but nitrate and perchlorate were
      less effective. The use of chlorate as a means to promote oil mineralization in
      situ may be a promising means to remediate contaminated salt marshes while
      preventing unwanted secondary impacts related to nutrient management as in the
      case of nitrate amendments.

PMID- 25854212
TI  - The battle of health with environmental evils of Asian countries: promises to
      keep.
AB  - The objective of the study is to examine the relationship between environmental
      indicators and health expenditures in the panel of five selected Asian countries,
      over the period of 2000-2013. The study used panel cointegration technique for
      evaluating the nexus between environment and health in the region. The results
      show that energy demand, forest area, and GDP per unit use of energy have a
      significant and positive impact on increasing health expenditures in the region.
      These results have been confirmed by single equation panel cointegration
      estimators, i.e., fully modified ordinary least squares (FMOLS), dynamic OLS
      (DOLS), and canonical cointegrating regression (CCR) estimators. In addition, the
      study used robust least squares regression to confirm the generalizability of the
      results in Asian context. All these estimators indicate that environmental
      indicators escalate the health expenditures per capita in a region; therefore,
      Asian countries should have to upsurge health expenditures for safeguard from
      environmental evils in a region. 

PMID- 25854213
TI  - Enteral tube feeding for cystic fibrosis.
AB  - BACKGROUND: Enteral tube feeding is routinely used in many cystic fibrosis
      centres when oral dietary and supplement intake has failed to achieve an adequate
      nutritional status. The use of this method of feeding is assessed on an
      individual basis taking into consideration the patients age and clinical status.
      OBJECTIVES: To examine the evidence that in people with cystic fibrosis,
      supplemental enteral tube feeding improves nutritional status, respiratory
      function, and quality of life without significant adverse effects. SEARCH
      METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group
      Trials Register which comprises references identified from comprehensive
      electronic database searches and handsearches of relevant journals and abstract
      books of conference proceedings. We also contacted the companies that market
      enteral feeds and reviewed their databases.Date of the most recent search of the
      Group's Cystic Fibrosis Trials Register: 13 February 2015.Date of the most recent
      hand search of PubMed and conference abstract books: 13 February 2015. SELECTION
      CRITERIA: All randomised controlled trials comparing supplemental enteral tube
      feeding for one month or longer with no specific intervention in people with
      cystic fibrosis. DATA COLLECTION AND ANALYSIS: The searches identified 38 trials;
      however, none were eligible for inclusion in this review. MAIN RESULTS: There are
      no trials included in this review. AUTHORS' CONCLUSIONS: Supplemental enteral
      tube feeding is widely used throughout the world to improve nutritional status in
      people with cystic fibrosis. The methods mostly used, nasogastric or gastrostomy
      feeding, are expensive and may have a negative effect on self-esteem and body
      image. Reported use of enteral tube feeding suggests that it results in
      nutritional and respiratory improvement; but, efficacy has not been fully
      assessed by randomised controlled trials. It is acknowledged, however, that
      performing a randomised controlled trial would be difficult due to the ethics of
      withholding an intervention in a group of patients whose nutritional status
      necessitates it.

PMID- 25854214
TI  - Co3O4-based binder-free cathodes for lithium-oxygen batteries with improved
      cycling stability.
AB  - A novel binder-free electrode for lithium-oxygen batteries has been prepared by
      electrodepositing a Co3O4 layer onto a pretreated TiO2 fiber mesh, formed on
      nickel foam by an electrospinning method. The Co3O4 depositing layer is composed
      of Co3O4 nanoflakes, forming a uniform flower-like porous structure. The Co3O4
      nanoflakes within the depositing layer provide a large amount of catalytic active
      sites for oxygen evolution and reduction reactions. The three-dimensional porous
      network of the Co3O4 depositing layer can not only facilitate the transportation
      of ions and electrolyte within the electrode, but also provide plenty of space to
      accommodate Li2O2 species formed during the discharge process. The Co3O4 spheres
      embedded in the TiO2 fiber mesh, formed by the treatment of a suspension of
      cobaltammine precipitate, function as anchors to prevent the detachment of the
      Co3O4 layer from the current collector, resulting in excellent structural and
      cycling stability. Only a slight specific capacity decay is observed at full
      discharge/charge after 80 cycles. This work demonstrates the important factors in
      the preparation of binder-free cathodes for high performance lithium-oxygen
      batteries. 

PMID- 25854215
TI  - Typical exposure parameters, organ doses and effective doses for endovascular
      aortic aneurysm repair: Comparison of Monte Carlo simulations and direct
      measurements with an anthropomorphic phantom.
AB  - OBJECTIVES: Radiation exposure of patients during endovascular aneurysm repair
      (EVAR) procedures ranks in the upper sector of medical exposure. Thus, estimation
      of radiation doses achieved during EVAR is of great importance. MATERIAL AND
      METHODS: Organ doses (OD) and effective doses (ED) administered to 17 patients
      receiving EVAR were determined (1) from the exposure parameters by performing
      Monte Carlo simulations in mathematical phantoms and (2) by measurements with
      thermoluminescent dosimeters in a physical anthropomorphic phantom. RESULTS: The
      mean fluoroscopy time was 26 min, the mean dose area product was 24995 cGy cm2.
      The mean ED was 34.8 mSv, ODs up to 626 mSv were found. Whereas digital
      subtraction angiographies (DSA) and fluoroscopies each contributed about 50% to
      the cumulative ED, the ED rates of DSAs were found to be ten times higher than
      those of fluoroscopies. Doubling of the field size caused an ED rate enhancement
      up to a factor of 3. CONCLUSION: EVAR procedures cause high radiation exposure
      levels that exceed the values published thus far. As a consequence, (1) DSAs
      should be only performed when necessary and with a low image rate, (2)
      fluoroscopies should be kept as short as possible, and (3) field sizes should be
      minimized. KEY POINTS: * During endovascular aneurysm repair (EVAR) considerable
      patient doses are achieved. * For each EVAR procedure organ (OD) and effective
      (ED) doses were determined. * The mean ED was 34.8 mSv, the highest OD was 626
      mSv. * Number of DSAs, fluoroscopy durations and field sizes should be minimized.

PMID- 25854216
TI  - Chest Computed Tomography-Based Scoring of Thoracic Sarcoidosis: Inter-rater
      Reliability of CT Abnormalities.
AB  - PURPOSE: To determine inter-rater reliability of sarcoidosis-related computed
      tomography (CT) findings that can be used for scoring of thoracic sarcoidosis.
      MATERIALS AND METHODS: CT images of 51 patients with sarcoidosis were scored by
      five chest radiologists for various abnormal CT findings (22 in total)
      encountered in thoracic sarcoidosis. Using intra-class correlation coefficient
      (ICC) analysis, inter-rater reliability was analysed and reported according to
      the Guidelines for Reporting Reliability and Agreement Studies (GRRAS) criteria.
      A pre-specified sub-analysis was performed to investigate the effect of training.
      Scoring was trained in a distinct set of 15 scans in which all abnormal CT
      findings were represented. RESULTS: Median age of the 51 patients (36 men, 70%)
      was 43 years (range 26 - 64 years). All radiographic stages were present in this
      group. ICC ranged from 0.91 for honeycombing to 0.11 for nodular margin (sharp
      versus ill-defined). The ICC was above 0.60 in 13 of the 22 abnormal findings.
      Sub-analysis for the best-trained observers demonstrated an ICC improvement for
      all abnormal findings and values above 0.60 for 16 of the 22 abnormalities.
      CONCLUSIONS: In our cohort, reliability between raters was acceptable for 16
      thoracic sarcoidosis-related abnormal CT findings. KEY POINTS: * Thoracic
      sarcoidosis is common; knowledge on reliability of CT scoring is limited. *
      Scoring CT abnormalities in pulmonary sarcoidosis can achieve good inter-rater
      agreement. * CT scoring validation in thoracic sarcoidosis is important for
      diagnostic and prognostic studies.

PMID- 25854218
TI  - Perspective: Insight into reaction coordinates and dynamics from the potential
      energy landscape.
AB  - This perspective focuses on conceptual and computational aspects of the potential
      energy landscape framework. It has two objectives: first to summarise some key
      developments of the approach and second to illustrate how such techniques can be
      applied using a specific example that exploits knowledge of pathways. Recent
      developments in theory and simulation within the landscape framework are first
      outlined, including methods for structure prediction, analysis of global
      thermodynamic properties, and treatment of rare event dynamics. We then develop a
      connection between the kinetic transition network treatment of dynamics and a
      potential of mean force defined by a reaction coordinate. The effect of
      projection from the full configuration space to low dimensionality is illustrated
      for an atomic cluster. In this example, where a relatively successful structural
      order parameter is available, the principal change in cluster morphology is
      reproduced, but some details are not faithfully represented. In contrast, a
      profile based on configurations that correspond to the discrete path defined
      geometrically retains all the barriers and minima. This comparison provides
      insight into the physical origins of "friction" effects in low-dimensionality
      descriptions of dynamics based upon a reaction coordinate. 

PMID- 25854217
TI  - 18-F fluorodeoxyglucose uptake in positron emission tomography as a pathological
      grade predictor for renal clear cell carcinomas.
AB  - OBJECTIVES: To evaluate the usefulness of Fluorine-18 fluorodeoxyglucose positron
      emission tomography/computed tomography (18-F FDG-PET/CT) in the prediction of
      Fuhrman pathological grades of renal clear cell carcinoma (cRCC). METHODS: This
      retrospective study was approved by our institutional review board, and written
      informed consent was waived. Thirty-one patients with pathologically proven cRCC
      underwent 18-F FDG-PET/CT for tumour staging. Maximum standardized uptake value
      of cRCC (tumour SUVmax) and mean SUV of the liver and spleen (liver and spleen
      SUVmean) were measured by two independent observers. Tumour SUVmax, tumour-to
      liver SUV ratio, and tumour-to-spleen SUV ratio were correlated with the
      pathological grades. RESULTS: Logistic analysis demonstrated that only the tumour
      to-liver SUV ratio was a significant parameter for differentiating high-grade
      (Fuhrman grades 3 and 4) tumours from low-grade (Fuhrman grades 1 and 2) tumours
      (P = 0.007 and 0.010 for observers 1 and 2, respectively). Sensitivity,
      specificity, and positive and negative predictive values for detecting tumours of
      Fuhrman grades 3 and 4 were 64, 100, 100, and 77%, respectively, for observer 1,
      and 79, 88, 85, and 83%, respectively, for observer 2. CONCLUSIONS: The tumour-to
      liver SUV ratio with 18-F FDG-PET/CT appeared to be a valuable imaging biomarker
      in the prediction of high-grade cRCC. KEY POINTS: * Tumour SUV max was correlated
      with the Fuhrman grades. * High-grade tumours have significantly higher SUV max
      than low-grade tumours. * Tumour-to-liver SUV ratio is useful in the prediction
      of high-grade cRCC.

PMID- 25854219
TI  - Communication: unraveling the (4)He droplet-mediated soft-landing from ab initio
      assisted and time-resolved density functional simulations: Au@(4)He300/TiO2(110).
AB  - An ab-initio-based methodological scheme for He-surface interactions and zero
      temperature time-dependent density functional theory for superfluid (4)He
      droplets motion are combined to follow the short-time collision dynamics of the
      Au@(4)He300 system with the TiO2(110) surface. This composite approach
      demonstrates the (4)He droplet-assisted sticking of the metal species to the
      surface at low landing energy (below 0.15 eV/atom), thus providing the first
      theoretical evidence of the experimentally observed (4)He droplet-mediated soft
      landing deposition of metal nanoparticles on solid surfaces [Mozhayskiy et al.,
      J. Chem. Phys. 127, 094701 (2007) and Loginov et al., J. Phys. Chem. A 115, 7199
      (2011)]. 

PMID- 25854220
TI  - Communication: A simple full range analytical potential for H2b(3)?u (+), H-He
      (2)?(+), and He2 (1)?g (.).
AB  - The Tang-Toennies potential for the weakly interacting systems H2b(3)Sigmau (+),
      H-He (2)Sigma(+), and He2 (1)Sigmag (+) is extended down to the united atom limit
      of vanishing internuclear distance. A simple analytic expression connects the
      united atom limiting potential with the Tang-Toennies potential in the well
      region. The new potential model is compared with the most recent ab initio
      calculations for all three systems. The agreement is better than 20% (H2 and He2)
      or comparable with the differences in the available ab initio calculations (H-He)
      over six orders of magnitude corresponding to the entire range of internuclear
      distances. 

PMID- 25854221
TI  - Communication: Note on detailed balance in symmetrical quasi-classical models for
      electronically non-adiabatic dynamics.
AB  - It is noted that the recently developed symmetrical quasi-classical (SQC)
      treatment of the Meyer-Miller (MM) model for the simulation of electronically non
      adiabatic dynamics provides a good description of detailed balance, even though
      the dynamics which results from the classical MM Hamiltonian is "Ehrenfest
      dynamics" (i.e., the force on the nuclei is an instantaneous coherent average
      over all electronic states). This is seen to be a consequence of the SQC
      windowing methodology for "processing" the results of the trajectory calculation.
      For a particularly simple model discussed here, this is shown to be true
      regardless of the choice of windowing function employed in the SQC model, and for
      a more realistic full classical molecular dynamics simulation, it is seen to be
      maintained correctly for very long time. 

PMID- 25854222
TI  - Biased diffusion in three-dimensional comb-like structures.
AB  - In this paper, we study biased diffusion of point Brownian particles in a three
      dimensional comb-like structure formed by a main cylindrical tube with identical
      periodic cylindrical dead ends. It is assumed that the dead ends are thin
      cylinders whose radius is much smaller than both the radius of the main tube and
      the distance between neighboring dead ends. It is also assumed that in the main
      tube, the particle, in addition to its regular diffusion, moves with a uniform
      constant drift velocity. For such a system, we develop a formalism that allows us
      to derive analytical expressions for the Laplace transforms of the first two
      moments of the particle displacement along the main tube axis. Inverting these
      Laplace transforms numerically, one can find the time dependences of the two
      moments for arbitrary values of both the drift velocity and the dead-end length,
      including the limiting case of infinitely long dead ends, where the unbiased
      diffusion becomes anomalous at sufficiently long times. The expressions for the
      Laplace transforms are used to find the effective drift velocity and diffusivity
      of the particle as functions of its drift velocity in the main tube and the tube
      geometric parameters. As might be expected from common-sense arguments, the
      effective drift velocity monotonically decreases from the initial drift velocity
      to zero as the dead-end length increases from zero to infinity. The effective
      diffusivity is a more complex, non-monotonic function of the dead-end length. As
      this length increases from zero to infinity, the effective diffusivity first
      decreases, reaches a minimum, and then increases approaching a plateau value
      which is proportional to the square of the particle drift velocity in the main
      tube. 

PMID- 25854223
TI  - A parallel algorithm for step- and chain-growth polymerization in molecular
      dynamics.
AB  - Classical Molecular Dynamics (MD) simulations provide insight into the properties
      of many soft-matter systems. In some situations, it is interesting to model the
      creation of chemical bonds, a process that is not part of the MD framework. In
      this context, we propose a parallel algorithm for step- and chain-growth
      polymerization that is based on a generic reaction scheme, works at a given
      intrinsic rate and produces continuous trajectories. We present an implementation
      in the ESPResSo++ simulation software and compare it with the corresponding
      feature in LAMMPS. For chain growth, our results are compared to the existing
      simulation literature. For step growth, a rate equation is proposed for the
      evolution of the crosslinker population that compares well to the simulations for
      low crosslinker functionality or for short times. 

PMID- 25854224
TI  - Boltzmann-conserving classical dynamics in quantum time-correlation functions:
      "Matsubara dynamics".
AB  - We show that a single change in the derivation of the linearized semiclassical
      initial value representation (LSC-IVR or "classical Wigner approximation")
      results in a classical dynamics which conserves the quantum Boltzmann
      distribution. We rederive the (standard) LSC-IVR approach by writing the (exact)
      quantum time-correlation function in terms of the normal modes of a free ring
      polymer (i.e., a discrete imaginary-time Feynman path), taking the limit that the
      number of polymer beads N -> infinity, such that the lowest normal-mode
      frequencies take their "Matsubara" values. The change we propose is to truncate
      the quantum Liouvillian, not explicitly in powers of h(2) at h(0) (which gives
      back the standard LSC-IVR approximation), but in the normal-mode derivatives
      corresponding to the lowest Matsubara frequencies. The resulting "Matsubara"
      dynamics is inherently classical (since all terms O(h(2)) disappear from the
      Matsubara Liouvillian in the limit N -> infinity) and conserves the quantum
      Boltzmann distribution because the Matsubara Hamiltonian is symmetric with
      respect to imaginary-time translation. Numerical tests show that the Matsubara
      approximation to the quantum time-correlation function converges with respect to
      the number of modes and gives better agreement than LSC-IVR with the exact
      quantum result. Matsubara dynamics is too computationally expensive to be applied
      to complex systems, but its further approximation may lead to practical methods. 

PMID- 25854225
TI  - Efficient calculation of integrals in mixed ramp-Gaussian basis sets.
AB  - Algorithms for the efficient calculation of two-electron integrals in the newly
      developed mixed ramp-Gaussian basis sets are presented, alongside a Fortran90
      implementation of these algorithms, RampItUp. These new basis sets have
      significant potential to (1) give some speed-up (estimated at up to 20% for large
      molecules in fully optimised code) to general-purpose Hartree-Fock (HF) and
      density functional theory quantum chemistry calculations, replacing all-Gaussian
      basis sets, and (2) give very large speed-ups for calculations of core-dependent
      properties, such as electron density at the nucleus, NMR parameters, relativistic
      corrections, and total energies, replacing the current use of Slater basis
      functions or very large specialised all-Gaussian basis sets for these purposes.
      This initial implementation already demonstrates roughly 10% speed-ups in HF/R
      31G calculations compared to HF/6-31G calculations for large linear molecules,
      demonstrating the promise of this methodology, particularly for the second
      application. As well as the reduction in the total primitive number in R-31G
      compared to 6-31G, this timing advantage can be attributed to the significant
      reduction in the number of mathematically complex intermediate integrals after
      modelling each ramp-Gaussian basis-function-pair as a sum of ramps on a single
      atomic centre. 

PMID- 25854226
TI  - Roles of dynamical symmetry breaking in driving oblate-prolate transitions of
      atomic clusters.
AB  - This paper explores the driving mechanisms for structural transitions of atomic
      clusters between oblate and prolate isomers. We employ the hyperspherical
      coordinates to investigate structural dynamics of a seven-atom cluster at a
      coarse-grained level in terms of the dynamics of three gyration radii and three
      principal axes, which characterize overall mass distributions of the cluster.
      Dynamics of gyration radii is governed by two kinds of forces. One is the
      potential force originating from the interactions between atoms. The other is the
      dynamical forces called the internal centrifugal forces, which originate from
      twisting and shearing motions of the system. The internal centrifugal force
      arising from twisting motions has an effect of breaking the symmetry between two
      gyration radii. As a result, in an oblate isomer, activation of the internal
      centrifugal force that has the effect of breaking the symmetry between the two
      largest gyration radii is crucial in triggering structural transitions into
      prolate isomers. In a prolate isomer, on the other hand, activation of the
      internal centrifugal force that has the effect of breaking the symmetry between
      the two smallest gyration radii is crucial in triggering structural transitions
      into oblate isomers. Activation of a twisting motion that switches the movement
      patterns of three principal axes is also important for the onset of structural
      transitions between oblate and prolate isomers. Based on these trigger
      mechanisms, we finally show that selective activations of specific gyration radii
      and twisting motions, depending on the isomer of the cluster, can effectively
      induce structural transitions of the cluster. The results presented here could
      provide further insights into the control of molecular reactions. 

PMID- 25854227
TI  - Thermodynamics of the polaron master equation at finite bias.
AB  - We study coherent transport through a double quantum dot. Its two electronic
      leads induce electronic matter and energy transport and a phonon reservoir
      contributes further energy exchanges. By treating the system-lead couplings
      perturbatively, whereas the coupling to vibrations is treated non-perturbatively
      in a polaron-transformed frame, we derive a thermodynamic consistent low
      dimensional master equation. When the number of phonon modes is finite, a
      Markovian description is only possible when these couple symmetrically to both
      quantum dots. For a continuum of phonon modes however, also asymmetric couplings
      can be described with a Markovian master equation. We compute the electronic
      current and dephasing rate. The electronic current enables transport spectroscopy
      of the phonon frequency and displays signatures of Franck-Condon blockade. For
      infinite external bias but finite tunneling bandwidths, we find oscillations in
      the current as a function of the internal bias due to the electron-phonon
      coupling. Furthermore, we derive the full fluctuation theorem and show its
      identity to the entropy production in the system. 

PMID- 25854228
TI  - Problem-free time-dependent variational principle for open quantum systems.
AB  - Methods of quantum nuclear wave-function dynamics have become very efficient in
      simulating large isolated systems using the time-dependent variational principle
      (TDVP). However, a straightforward extension of the TDVP to the density matrix
      framework gives rise to methods that do not conserve the energy in the isolated
      system limit and the total system population for open systems where only energy
      exchange with environment is allowed. These problems arise when the system
      density is in a mixed state and is simulated using an incomplete basis. Thus, the
      basis set incompleteness, which is inevitable in practical calculations, creates
      artificial channels for energy and population dissipation. To overcome this
      unphysical behavior, we have introduced a constrained Lagrangian formulation of
      TDVP applied to a non-stochastic open system Schrodinger equation [L. Joubert
      Doriol, I. G. Ryabinkin, and A. F. Izmaylov, J. Chem. Phys. 141, 234112 (2014)].
      While our formulation can be applied to any variational ansatz for the system
      density matrix, derivation of working equations and numerical assessment is done
      within the variational multiconfiguration Gaussian approach for a two-dimensional
      linear vibronic coupling model system interacting with a harmonic bath. 

PMID- 25854229
TI  - Experimental and theoretical determination of the plasmonic responses and shape
      distribution of colloidal metallic nanoparticles.
AB  - The optical properties of gold and silver nanoparticles (NPs) dispersed in water
      and distributed in shape are investigated by introducing a shape distributed
      effective medium theory (SDEMT). This model takes into account the variation of
      depolarization parameter induced by a NP shape distribution. Simulations show
      that the shape distribution induces an inhomogeneous broadening and a decrease of
      the amplitude of the plasmon band. The number of plasmon bands and their
      positions depend on both the mean value of depolarization parameter and the NP
      material. By fitting the measured absorption spectra with the SDEMT, we
      unambiguously demonstrate that the depolarization parameter distribution, i.e.,
      the shape distribution of nanoparticles can be deduced from absorption spectra. 

PMID- 25854230
TI  - General multi-group macroscopic modeling for thermo-chemical non-equilibrium gas
      mixtures.
AB  - This paper opens a new door to macroscopic modeling for thermal and chemical non
      equilibrium. In a game-changing approach, we discard conventional theories and
      practices stemming from the separation of internal energy modes and the Landau
      Teller relaxation equation. Instead, we solve the fundamental microscopic
      equations in their moment forms but seek only optimum representations for the
      microscopic state distribution function that provides converged and time accurate
      solutions for certain macroscopic quantities at all times. The modeling makes no
      ad hoc assumptions or simplifications at the microscopic level and includes all
      possible collisional and radiative processes; it therefore retains all non
      equilibrium fluid physics. We formulate the thermal and chemical non-equilibrium
      macroscopic equations and rate coefficients in a coupled and unified fashion for
      gases undergoing completely general transitions. All collisional partners can
      have internal structures and can change their internal energy states after
      transitions. The model is based on the reconstruction of the state distribution
      function. The internal energy space is subdivided into multiple groups in order
      to better describe non-equilibrium state distributions. The logarithm of the
      distribution function in each group is expressed as a power series in internal
      energy based on the maximum entropy principle. The method of weighted residuals
      is applied to the microscopic equations to obtain macroscopic moment equations
      and rate coefficients succinctly to any order. The model's accuracy depends only
      on the assumed expression of the state distribution function and the number of
      groups used and can be self-checked for accuracy and convergence. We show that
      the macroscopic internal energy transfer, similar to mass and momentum transfers,
      occurs through nonlinear collisional processes and is not a simple relaxation
      process described by, e.g., the Landau-Teller equation. Unlike the classical
      vibrational energy relaxation model, which can only be applied to molecules, the
      new model is applicable to atoms, molecules, ions, and their mixtures. Numerical
      examples and model validations are carried out with two gas mixtures using the
      maximum entropy linear model: one mixture consists of nitrogen molecules
      undergoing internal excitation and dissociation and the other consists of
      nitrogen atoms undergoing internal excitation and ionization. Results show that
      the original hundreds to thousands of microscopic equations can be reduced to two
      macroscopic equations with almost perfect agreement for the total number density
      and total internal energy using only one or two groups. We also obtain good
      prediction of the microscopic state populations using 5-10 groups in the
      macroscopic equations. 

PMID- 25854231
TI  - Obtaining the Hessian from the force covariance matrix: Application to
      crystalline explosives PETN and RDX.
AB  - We show that for solids the effective Hessian matrix, averaged over the canonical
      ensemble, can be calculated from the force covariance matrix. This effective
      Hessian reduces to the standard Hessian as the temperature approaches zero, while
      at finite temperatures it implicitly includes anharmonic corrections. As a case
      study, we calculate the effective Hessians and the corresponding normal mode
      eigenvectors and frequencies for the crystalline organic explosives
      pentaerythritol tetranitrate and alpha-1,3,5-trinitro-1,3,5-triazacyclohexane.
      The resulting normal mode frequencies are compared to those obtained by
      diagonalizing the standard Hessian matrix of second derivatives in Cartesian
      displacements about the potential energy minimum. Effects of temperature and
      statistical noise on the effective Hessians and normal mode frequencies are
      discussed. 

PMID- 25854232
TI  - Semiclassical Wigner theory of photodissociation in three dimensions: Shedding
      light on its basis.
AB  - The semiclassical Wigner theory (SCWT) of photodissociation dynamics, initially
      proposed by Brown and Heller [J. Chem. Phys. 75, 186 (1981)] in order to describe
      state distributions in the products of direct collinear photodissociations, was
      recently extended to realistic three-dimensional triatomic processes of the same
      type [Arbelo-Gonzalez et al., Phys. Chem. Chem. Phys. 15, 9994 (2013)]. The
      resulting approach, which takes into account rotational motions in addition to
      vibrational and translational ones, was applied to a triatomic-like model of
      methyl iodide photodissociation and its predictions were found to be in nearly
      quantitative agreement with rigorous quantum results, but at a much lower
      computational cost, making thereby SCWT a potential tool for the study of
      polyatomic reaction dynamics. Here, we analyse the main reasons for this
      agreement by means of an elementary model of fragmentation explicitly dealing
      with the rotational motion only. We show that our formulation of SCWT makes it a
      semiclassical approximation to an approximate planar quantum treatment of the
      dynamics, both of sufficient quality for the whole treatment to be satisfying. 

PMID- 25854233
TI  - The variational subspace valence bond method.
AB  - The variational subspace valence bond (VSVB) method based on overlapping orbitals
      is introduced. VSVB provides variational support against collapse for the
      optimization of overlapping linear combinations of atomic orbitals (OLCAOs) using
      modified orbital expansions, without recourse to orthogonalization. OLCAO have
      the advantage of being naturally localized, chemically intuitive (to individually
      model bonds and lone pairs, for example), and transferrable between different
      molecular systems. Such features are exploited to avoid key computational
      bottlenecks. Since the OLCAO can be doubly occupied, VSVB can access very large
      problems, and calculations on systems with several hundred atoms are presented. 

PMID- 25854234
TI  - How electronic dynamics with Pauli exclusion produces Fermi-Dirac statistics.
AB  - It is important that any dynamics method approaches the correct population
      distribution at long times. In this paper, we derive a one-body reduced density
      matrix dynamics for electrons in energetic contact with a bath. We obtain a
      remarkable equation of motion which shows that in order to reach equilibrium
      properly, rates of electron transitions depend on the density matrix. Even though
      the bath drives the electrons towards a Boltzmann distribution, hole blocking
      factors in our equation of motion cause the electronic populations to relax to a
      Fermi-Dirac distribution. These factors are an old concept, but we show how they
      can be derived with a combination of time-dependent perturbation theory and the
      extended normal ordering of Mukherjee and Kutzelnigg for a general electronic
      state. The resulting non-equilibrium kinetic equations generalize the usual
      Redfield theory to many-electron systems, while ensuring that the orbital
      occupations remain between zero and one. In numerical applications of our
      equations, we show that relaxation rates of molecules are not constant because of
      the blocking effect. Other applications to model atomic chains are also presented
      which highlight the importance of treating both dephasing and relaxation.
      Finally, we show how the bath localizes the electron density matrix. 

PMID- 25854235
TI  - Comparison among Magnus/Floquet/Fer expansion schemes in solid-state NMR.
AB  - We here revisit expansion schemes used in nuclear magnetic resonance (NMR) for
      the calculation of effective Hamiltonians and propagators, namely, Magnus,
      Floquet, and Fer expansions. While all the expansion schemes are powerful methods
      there are subtle differences among them. To understand the differences, we
      performed explicit calculation for heteronuclear dipolar decoupling, cross
      polarization, and rotary-resonance experiments in solid-state NMR. As the
      propagator from the Fer expansion takes the form of a product of sub-propagators,
      it enables us to appreciate effects of time-evolution under Hamiltonians with
      different orders separately. While 0th-order average Hamiltonian is the same for
      the three expansion schemes with the three cases examined, there is a case that
      the 2nd-order term for the Magnus/Floquet expansion is different from that
      obtained with the Fer expansion. The difference arises due to the separation of
      the 0th-order term in the Fer expansion. The separation enables us to appreciate
      time-evolution under the 0th-order average Hamiltonian, however, for that
      purpose, we use a so-called left-running Fer expansion. Comparison between the
      left-running Fer expansion and the Magnus expansion indicates that the sign of
      the odd orders in Magnus may better be reversed if one would like to consider its
      effect in order. 

PMID- 25854236
TI  - Line broadening interference for high-resolution nuclear magnetic resonance
      spectra under inhomogeneous magnetic fields.
AB  - Nuclear magnetic resonance spectroscopy serves as an important tool for analyzing
      chemicals and biological metabolites. However, its performance is subject to the
      magnetic-field homogeneity. Under inhomogeneous fields, peaks are broadened to
      overlap each other, introducing difficulties for assignments. Here, we propose a
      method termed as line broadening interference (LBI) to provide high-resolution
      information under inhomogeneous magnetic fields by employing certain gradients in
      the indirect dimension to interfere the magnetic-field inhomogeneity. The
      conventional spectral-line broadening is thus interfered to be non-diagonal,
      avoiding the overlapping among adjacent resonances. Furthermore, an inhomogeneity
      correction algorithm is developed based on pattern recognition to recover the
      high-resolution information from LBI spectra. Theoretical deductions are
      performed to offer systematic and detailed analyses on the proposed method.
      Moreover, experiments are conducted to prove the feasibility of the proposed
      method for yielding high-resolution spectra in inhomogeneous magnetic fields. 

PMID- 25854237
TI  - The ionic states of iodobenzene studied by photoionization and ab initio
      configuration interaction and DFT computations.
AB  - New valence electron photoelectron spectra of iodobenzene obtained using
      synchrotron radiation have been recorded. Ionization energies (IEs) determined
      using multi-configuration SCF calculation (MCSCF) procedures confirmed the
      adiabatic IE order as: X(2)B1<A(2)A2<B(2)B2<C(2)B1. Although it is convenient to
      retain C2v labelling, there is an evidence that minor distortion to CS symmetry
      occurs at the MCSCF level for the C state. The fifth ionization process shown to
      be D(2)A1 exhibits dissociation to C6H5 (+) + I both in the experimental and
      theoretical studies. The calculated Franck-Condon vibrational spectral envelopes,
      including hot band contributions, for the first four ionic states reproduce the
      observed peak positions and intensities with reasonable accuracy. In order to
      simulate the observed spectra, different bandwidths are required for different
      states. The increase in the required bandwidths for the A(2)A2 and B(2)B2 states
      is attributed to internal conversion to lower-lying states. The presence of
      relatively high intensity sequence bands leads to asymmetry of each of the X(2)B1
      state bands. 

PMID- 25854238
TI  - Interpretation of the vacuum ultraviolet photoabsorption spectrum of iodobenzene
      by ab initio computations.
AB  - Identification of many Rydberg states in iodobenzene, especially from the first
      and fourth ionization energies (IE1 and IE4, X(2)B1 and C(2)B1), has become
      possible using a new ultraviolet (UV) and vacuum-ultraviolet (VUV) absorption
      spectrum, in the region 29 000-87 000 cm(-1) (3.60-10.79 eV), measured at room
      temperature with synchrotron radiation. A few Rydberg states based on IE2
      (A(2)A2) were found, but those based on IE3 (B(2)B2) are undetectable. The almost
      complete absence of observable Rydberg states relating to IE2 and IE3 (A(2)A2 and
      B(2)B2, respectively) is attributed to them being coupled to the near-continuum,
      high-energy region of Rydberg series converging on IE1. Theoretical studies of
      the UV and VUV spectra used both time-dependent density functional (TDDFT) and
      multi-reference multi-root doubles and singles-configuration interaction methods.
      The theoretical adiabatic excitation energies, and their corresponding
      vibrational profiles, gave a satisfactory interpretation of the experimental
      results. The calculations indicate that the UV onset contains both 1(1)B1 and
      1(1)B2 states with very low oscillator strength, while the 2(1)B1 state was found
      to lie under the lowest pipi(*) 1(1)A1 state. All three of these (1)B1 and (1)B2
      states are excitations into low-lying sigma(*) orbitals. The strongest VUV band
      near 7 eV contains two very strong pipi(*) valence states, together with other
      weak contributors. The lowest Rydberg 4b16s state (3(1)B1) is very evident as a
      sharp multiplet near 6 eV; its position and vibrational structure are well
      reproduced by the TDDFT results. 

PMID- 25854239
TI  - Superfluid response of two-dimensional parahydrogen clusters in confinement.
AB  - We study by computer simulations the effect of confinement on the superfluid
      properties of small two-dimensional (2D) parahydrogen clusters. For clusters of
      fewer than twenty molecules, the superfluid response in the low temperature limit
      is found to remain comparable in magnitude to that of free clusters, within a
      rather wide range of depth and size of the confining well. The resilience of the
      superfluid response is attributable to the "supersolid" character of these
      clusters. We investigate the possibility of establishing a bulk 2D superfluid
      "cluster crystal" phase of p-H2, in which a global superfluid response would
      arise from tunnelling of molecules across adjacent unit cells. The computed
      energetics suggests that for clusters of about ten molecules, such a phase may be
      thermodynamically stable against the formation of the equilibrium insulating
      crystal, for values of the cluster crystal lattice constant possibly allowing
      tunnelling across adjacent unit cells. 

PMID- 25854240
TI  - Simulation of the elementary evolution operator with the motional states of an
      ion in an anharmonic trap.
AB  - Following a recent proposal of L. Wang and D. Babikov [J. Chem. Phys. 137, 064301
      (2012)], we theoretically illustrate the possibility of using the motional states
      of a Cd(+) ion trapped in a slightly anharmonic potential to simulate the single
      particle time-dependent Schrodinger equation. The simulated wave packet is
      discretized on a spatial grid and the grid points are mapped on the ion motional
      states which define the qubit network. The localization probability at each grid
      point is obtained from the population in the corresponding motional state. The
      quantum gate is the elementary evolution operator corresponding to the time
      dependent Schrodinger equation of the simulated system. The corresponding matrix
      can be estimated by any numerical algorithm. The radio-frequency field which is
      able to drive this unitary transformation among the qubit states of the ion is
      obtained by multi-target optimal control theory. The ion is assumed to be cooled
      in the ground motional state, and the preliminary step consists in initializing
      the qubits with the amplitudes of the initial simulated wave packet. The time
      evolution of the localization probability at the grids points is then obtained by
      successive applications of the gate and reading out the motional state
      population. The gate field is always identical for a given simulated potential,
      only the field preparing the initial wave packet has to be optimized for
      different simulations. We check the stability of the simulation against
      decoherence due to fluctuating electric fields in the trap electrodes by applying
      dissipative Lindblad dynamics. 

PMID- 25854241
TI  - Photoelectron spectroscopy of B4O4 (-): Dual 3c-4e pi hyperbonds and rhombic 4c
      4e o-bond in boron oxide clusters.
AB  - Gas-phase anion photoelectron spectroscopy (PES) is combined with global
      structural searches and electronic structure calculations at the hybrid Becke 3
      parameter exchange functional and Lee-Yang-Parr correlation functional (B3LYP)
      and single-point coupled-cluster with single, double, and perturbative triple
      excitations (CCSD(T)) levels to probe the structural and electronic properties
      and chemical bonding of the B4O4 (0/-) clusters. The measured PES spectra of B4O4
      (-) exhibit a major band with the adiabatic and vertical detachment energies (ADE
      and VDE) of 2.64 +/- 0.10 and 2.81 +/- 0.10 eV, respectively, as well as a weak
      peak with the ADE and VDE of 1.42 +/- 0.08 and 1.48 +/- 0.08 eV. The former band
      proves to correspond to the Y-shaped global minimum of Cs B4O4 (-) ((2)A"), with
      the calculated ADE/VDE of 2.57/2.84 eV at the CCSD(T) level, whereas the weak
      band is associated with the second lowest-energy, rhombic isomer of D2h B4O4 (-)
      ((2)B2g) with the predicted ADE/VDE of 1.43/1.49 eV. Both anion structures are
      planar, featuring a B atom or a B2O2 core bonded with terminal BO and/or BO2
      groups. The same Y-shaped and rhombic structures are also located for the B4O4
      neutral cluster, albeit with a reversed energy order. Bonding analyses reveal
      dual three-center four-electron (3c-4e) pi hyperbonds in the Y-shaped B4O4 (0/-)
      clusters and a four-center four-electron (4c-4e) pi bond, that is, the so-called
      o-bond in the rhombic B4O4 (0/-) clusters. This work is the first experimental
      study on a molecular system with an o-bond. 

PMID- 25854242
TI  - Infrared rovibrational spectroscopy of OH-C2H2 in (4)He nanodroplets: Parity
      splitting due to partially quenched electronic angular momentum.
AB  - The T-shaped OH-C2H2 complex is formed in helium droplets via the sequential pick
      up and solvation of the monomer fragments. Rovibrational spectra of the a-type OH
      stretch and b-type antisymmetric CH stretch vibrations contain resolved parity
      splitting that reveals the extent to which electronic angular momentum of the OH
      moiety is quenched upon complex formation. The energy difference between the spin
      orbit coupled (2)B1 (A") and (2)B2 (A') electronic states is determined
      spectroscopically to be 216 cm(-1) in helium droplets, which is 13 cm(-1) larger
      than in the gas phase [Marshall et al., J. Chem. Phys. 121, 5845 (2004)]. The
      effect of the helium is rationalized as a difference in the solvation free
      energies of the two electronic states. This interpretation is motivated by the
      separation between the Q(3/2) and R(3/2) transitions in the infrared spectrum of
      the helium-solvated (2)Pi3/2 OH radical. Despite the expectation of a reduced
      rotational constant, the observed Q(3/2) to R(3/2) splitting is larger than in
      the gas phase by ~0.3 cm(-1). This observation can be accounted for
      quantitatively by assuming the energetic separation between (2)Pi3/2 and (2)Pi1/2
      manifolds is increased by ~40 cm(-1) upon helium solvation. 

PMID- 25854243
TI  - Evaluation of the exothermicity of the chemi-ionization reaction Sm + O -> SmO(+)
      + e(.).
AB  - The exothermicity of the chemi-ionization reaction Sm + O -> SmO(+) + e(-) has
      been re-evaluated through the combination of several experimental methods. The
      thermal reactivity (300-650 K) of Sm(+) and SmO(+) with a range of species
      measured using a selected ion flow tube-mass spectrometer apparatus is reported
      and provides limits for the bond strength of SmO(+), 5.661 eV <= D0(Sm(+)-O) <=
      6.500 eV. A more precise value is measured to be 5.725 +/- 0.07 eV, bracketed by
      the observed reactivity of Sm(+) and SmO(+) with several species using a guided
      ion beam tandem mass spectrometer (GIBMS). Combined with the established Sm
      ionization energy (IE), this value indicates an exothermicity of the title
      reaction of 0.08 +/- 0.07 eV, ~0.2 eV smaller than previous determinations. In
      addition, the ionization energy of SmO has been measured by resonantly enhanced
      two-photon ionization and pulsed-field ionization zero kinetic energy
      photoelectron spectroscopy to be 5.7427 +/- 0.0006 eV, significantly higher than
      the literature value. Combined with literature bond energies of SmO, this value
      indicates an exothermicity of the title reaction of 0.14 +/- 0.17 eV, independent
      from and in agreement with the GIBMS result presented here. The evaluated
      thermochemistry also suggests that D0(SmO) = 5.83 +/- 0.07 eV, consistent with
      but more precise than the literature values. Implications of these results for
      interpretation of chemical release experiments in the thermosphere are discussed.

PMID- 25854244
TI  - Photoelectron spectroscopy and theoretical studies of gaseous uranium
      hexachlorides in different oxidation states: UCl6 (q-) (q = 0-2).
AB  - Uranium chlorides are important in actinide chemistry and nuclear industries, but
      their chemical bonding and many physical and chemical properties are not well
      understood yet. Here, we report the first experimental observation of two gaseous
      uranium hexachloride anions, UCl6 (-) and UCl6 (2-), which are probed by
      photoelectron spectroscopy in conjunction with quantum chemistry calculations.
      The electron affinity of UCl6 is measured for the first time as +5.3 eV; its
      second electron affinity is measured to be +0.60 eV from the photoelectron
      spectra of UCl6 (2-). We observe that the detachment cross sections of the 5f
      electrons are extremely weak in the visible and UV energy ranges. It is found
      that the one-electron one-determinental molecular orbital picture and Koopmans'
      theorem break down for the strongly internally correlated U-5f(2) valence shell
      of tetravalent U(+4) in UCl6 (2-). The calculated adiabatic and vertical electron
      detachment energies from ab initio calculations agree well with the experimental
      observations. Electronic structure and chemical bonding in the uranium
      hexachloride species UCl6 (2-) to UCl6 are discussed as a function of the
      oxidation state of U. 

PMID- 25854245
TI  - Fourier-transform spectroscopy and potential construction of the (2)(1)Pi state
      in KCs.
AB  - The paper presents an empirical pointwise potential energy curve (PEC) of the
      (2)(1)Pi state of the KCs molecule constructed by applying the Inverted
      Perturbation Approach routine. The experimental term values in the energy range
      E(v', J') ? [15 407; 16 579] cm(-1) involved in the fit were based on Fourier
      Transform spectroscopy data obtained with 0.01 cm(-1) accuracy from the laser
      induced (2)(1)Pi -> X(1)Sigma(+) fluorescence spectra. Buffer gas Ar was used to
      facilitate the appearance of rotation relaxation lines in the spectra, thus
      enlarging the (2)(1)Pi data set and allowing determination of the Lambda
      splitting constants. The data set included vibrational v' ? [0, 28] and
      rotational J' ? [7, 274] quantum numbers covering about 67% of the potential
      well. The present PEC reproduces the overall set of data included in the fit with
      a standard deviation of 0.5 cm(-1). The obtained value of the Lambda-doubling
      constant q = + 1.8 * 10(-6) cm(-1) for J' > 50 and v' ? [0, 6] is in an excellent
      agreement with q = + 1.84 * 10(-6) cm(-1) reported in Kim, Lee, and Stolyarov [J.
      Mol. Spectrosc. 256, 57-67 (2009)]. 

PMID- 25854246
TI  - The energetic of (CH2F2)2 investigated by TDL IR spectroscopy and DFT
      computations: From collision induced relaxation of ro-vibrational transitions to
      non-covalent interactions.
AB  - Difluoromethane (CH2F2) is an atmospheric pollutant presenting strong absorptions
      within the 8-12 MUm atmospheric window, hence it can contribute to global
      warming. Its dimer, (CH2F2)2, is bound through weak hydrogen bonds (wHBs).
      Theoretically, wHBs are of paramount importance in biological systems, though
      their modeling at density functional theory (DFT) level requires dispersion
      correlations to be accounted for. In this work, the binding energy (3.1 +/- 0.5
      kcal mol(-1)) of (CH2F2)2 is experimentally derived from the foreign broadening
      coefficients of the monomer compound, collisionally perturbed by a range of
      damping gases. Measurements are carried out on CH2F2 ro-vibrational transitions
      by means of tunable diode laser spectroscopy. Six stationary points on the
      potential energy surface (PES) of the dimer are investigated at DFT level by
      using some of the last generation density functionals (DFs). The Minnesota M06
      suite of functionals as well as range separated DFs and DFs augmented by the non
      local (NL) van der Waals (vdW) dispersion corrections are considered. DFT results
      are compared to reference values at the estimated complete basis set (CBS) limit
      of CCSD(T) theory (coupled cluster with singles and doubles augmented by a
      perturbational estimate of connected triples) and to the experimental binding
      energy. The M06-2X, M06-HF, VV10, BLYP-NL, and B3LYP-NL DFs reproduce CCSD(T)/CBS
      binding energies with a mean absolute deviation <0.4 kcal mol(-1) and about the
      same deviation from the experimental value. The present results are of twofold
      relevance: (i) they show that binding energy of homodimers can be conveniently
      obtained from the monomer's foreign broadening coefficients and that the correct
      simulation of hydrogen bonds involved in (CH2F2)2 needs non-covalent interactions
      to be included into DFT; (ii) O2- and N2-pressure broadening parameters represent
      fundamental data for exploiting the efficacy of remote sensing measurements
      employed to retrieve temperature and concentration profiles of our atmosphere. 

PMID- 25854247
TI  - Ferroelectricity in high-density H2O ice.
AB  - The origin of longstanding anomalies in experimental studies of the dense solid
      phases of H2O ices VII, VIII, and X is examined using a combination of first
      principles theoretical methods. We find that a ferroelectric variant of ice VIII
      is energetically competitive with the established antiferroelectric form under
      pressure. The existence of domains of the ferroelectric form within anti
      ferroelectric ice can explain previously observed splittings in x-ray diffraction
      data. The ferroelectric form is stabilized by density and is accompanied by the
      onset of spontaneous polarization. The presence of local electric fields triggers
      the preferential parallel orientation of the water molecules in the structure,
      which could be stabilized in bulk using new high-pressure techniques. 

PMID- 25854248
TI  - Effects of confinement on anomalies and phase transitions of core-softened
      fluids.
AB  - We use molecular dynamics simulations to study how the confinement affects the
      dynamic, thermodynamic, and structural properties of a confined anomalous fluid.
      The fluid is modeled using an effective pair potential derived from the ST4
      atomistic model for water. This system exhibits density, structural, and
      dynamical anomalies, and the vapor-liquid and liquid-liquid critical points
      similar to the quantities observed in bulk water. The confinement is modeled both
      by smooth and structured walls. The temperatures of extreme density and diffusion
      for the confined fluid show a shift to lower values while the pressures move to
      higher amounts for both smooth and structured confinements. In the case of smooth
      walls, the critical points and the limit between fluid and amorphous phases show
      a non-monotonic change in the temperatures and pressures when the nanopore size
      is increase. In the case of structured walls, the pressures and temperatures of
      the critical points varies monotonically with the pore size. Our results are
      explained on basis of the competition between the different length scales of the
      fluid and the wall-fluid interaction. 

PMID- 25854249
TI  - Composition dependent structural organization in trihexyl(tetradecyl)phosphonium
      chloride ionic liquid-methanol mixtures.
AB  - This article reports results from the molecular dynamics simulations on the
      structural arrangement of the ions and molecules in the mixtures of
      trihexyl(tetradecyl)phosphonium chloride ([P666,14 (+)][Cl(-)]) ionic liquid (IL)
      and methanol (MeOH) over the entire composition range. Effects of composition on
      the charge and polarity orderings have been investigated via computation of X-ray
      scattering structure function, S(q), and by using a partitioning scheme proposed
      for such multi-component mixtures. Except for the neat methanol liquid, the total
      S(q) shows two peaks in its intermolecular region for all the mole-fractions. The
      lowest q peak is dominated primarily by anion-anion, cation-anion, and methanol
      anion correlations. Our results signify that the methanol bulk structure, which
      predominantly has short-distance characteristic correlations and is governed by
      polar group of methanol, is retained for xIL <= 0.1. Then, the mixture goes
      through gradual structural changes from methanol-like to the IL-like for 0.1 <
      xIL <= 0.7. The dipolar interaction between methanol molecules weakens in this
      range, and the structural landscape of the mixture is steered by strong ion-ion,
      anion-methanol, and nonpolar interactions. The IL-like structural arrangement is
      virtually recovered for xIL > 0.7. At all the compositions studied, while the
      cation head groups are predominantly solvated by anions and subsequently by
      methanol molecules, the polar hydroxyl group of methanol is preferentially
      solvated by the anions. The radial distribution functions of selected pair of
      atomic species have also confirmed these observations. 

PMID- 25854250
TI  - Thermal stability of vapor-deposited stable glasses of an organic semiconductor.
AB  - Vapor-deposited organic glasses can show enhanced kinetic stability relative to
      liquid-cooled glasses. When such stable glasses of model glassformers are
      annealed above the glass transition temperature Tg, they lose their thermal
      stability and transform into the supercooled liquid via constant velocity
      propagating fronts. In this work, we show that vapor-deposited glasses of an
      organic semiconductor, N,N'-bis(3-methylphenyl)-N,N'-diphenylbenzidine (TPD),
      also transform via propagating fronts. Using spectroscopic ellipsometry and a new
      high-throughput annealing protocol, we measure transformation front velocities
      for TPD glasses prepared with substrate temperatures (TSubstrate) from 0.63 to
      0.96 Tg, at many different annealing temperatures. We observe that the front
      velocity varies by over an order of magnitude with TSubstrate, while the
      activation energy remains constant. Using dielectric spectroscopy, we measure the
      structural relaxation time of supercooled TPD. We find that the mobility of the
      liquid and the structure of the glass are independent factors in controlling the
      thermal stability of TPD films. In comparison to model glassformers, the
      transformation fronts of TPD have similar velocities and a similar dependence on
      TSubstrate, suggesting universal behavior. These results may aid in designing
      active layers in organic electronic devices with improved thermal stability. 

PMID- 25854251
TI  - Orientational order as the origin of the long-range hydrophobic effect.
AB  - The long range attractive force between two hydrophobic surfaces immersed in
      water is observed to decrease exponentially with their separation-this distance
      dependence of effective force is known as the hydrophobic force law (HFL). We
      explore the microscopic origin of HFL by studying distance-dependent attraction
      between two parallel rods immersed in 2D Mercedes Benz model of water. This model
      is found to exhibit a well-defined HFL. Although the phenomenon is conventionally
      explained by density-dependent theories, we identify orientation, rather than
      density, as the relevant order parameter. The range of density variation is
      noticeably shorter than that of orientational heterogeneity. The latter is
      comparable to the observed distances of hydrophobic force. At large separation,
      attraction between the rods arises primarily from a destructive interference
      among the inwardly propagating oppositely oriented heterogeneity generated in
      water by the two rods. As the rods are brought closer, the interference increases
      leading to a decrease in heterogeneity and concomitant decrease in free energy of
      the system, giving rise to the effective attraction. We notice formation of
      hexagonal ice-like structures at the onset of attractive region which suggests
      that metastable free energy minimum may play a role in the origin of HFL. 

PMID- 25854252
TI  - Slip length crossover on a graphene surface.
AB  - Using equilibrium and non-equilibrium molecular dynamics simulations, we study
      the flow of argon fluid above the critical temperature in a planar nanochannel
      delimited by graphene walls. We observe that, as a function of pressure, the slip
      length first decreases due to the decreasing mean free path of gas molecules,
      reaches the minimum value when the pressure is close to the critical pressure,
      and then increases with further increase in pressure. We demonstrate that the
      slip length increase at high pressures is due to the fact that the viscosity of
      fluid increases much faster with pressure than the friction coefficient between
      the fluid and the graphene. This behavior is clearly exhibited in the case of
      graphene due to a very smooth potential landscape originating from a very high
      atomic density of graphene planes. By contrast, on surfaces with lower atomic
      density, such as an (100) Au surface, the slip length for high fluid pressures is
      essentially zero, regardless of the nature of interaction between fluid and the
      solid wall. 

PMID- 25854253
TI  - Effect of microstructure on spontaneous polarization in amorphous solid water
      films.
AB  - Amorphous solid water (ASW) films grown by vapor deposition below 110 K develop
      negative surface voltages Vs with respect to the substrate. This polarization is
      due to a partial alignment of the water molecules during condensation. Kelvin
      probe measurements show that the magnitude of the surface potential, |Vs|,
      increases linearly with film thickness at a rate that decreases with increasing
      deposition temperature. |Vs| decreases with increasing deposition temperature and
      increasing incidence angle of the vapor source. After film growth, |Vs| decreases
      irreversibly by 80% when the ice film is heated to ~30 K above the deposition
      temperature. The measurements of |Vs| as a function of film porosity indicate
      that polarization in ASW is governed by incompletely coordinated water molecules,
      dangling with unbalanced dipoles at the internal surface of the pores and weakly
      aligned by the anisotropic film-vacuum interface. This idea is supported by the
      strikingly similar behavior of |Vs| and the infrared absorption due to the most
      pliable, two-coordinated surface molecules with annealing temperature. 

PMID- 25854254
TI  - Transitions between strongly correlated and random steady-states for catalytic CO
      oxidation on surfaces at high-pressure.
AB  - We explore simple lattice-gas reaction models for CO-oxidation on 1D and 2D
      periodic arrays of surface adsorption sites with CO adsorption and desorption,
      dissociative O2 adsorption and recombinative desorption (at low rate), and CO + O
      reaction to form CO2. Adspecies interactions are neglected, and adspecies
      diffusion is effectively absent. The models are motivated by studies of CO
      oxidation on RuO2(110) at high-pressures. Despite the lack of adspecies
      interactions, negligible adspecies diffusion results in kinetically induced
      spatial correlations. A transition occurs from a random primarily CO-populated
      steady-state at high CO-partial pressure, pCO, to a strongly correlated near-O
      covered steady-state for low pCO as noted by Matera et al. [J. Chem. Phys. 134,
      064713 (2011)]. In addition, we identify a second transition to a random near-O
      covered steady-state at very low pCO. Furthermore, we identify and analyze the
      slow "diffusive dynamics" for very low pCO and provide a detailed
      characterization of the crossover to the strongly correlated O-covered steady
      state as well as of the spatial correlations in that state. 

PMID- 25854255
TI  - A transition between bistable ice when coupling electric field and
      nanoconfinement.
AB  - The effects of an electric field on the phase behavior of water confined inside a
      nanoscale space were studied using molecular dynamics simulations. It was found
      that the diffusion coefficient of water reaches its maximum when value of the
      surfaces' charge is at the threshold, qc = 0.5e. This unexpected phenomenon was
      attributed to the intermediate state between two stable ice states induced by
      nanoconfinement and the electric field generated by charged surfaces,
      respectively. Our finding is helpful to understand electromelting and
      electrofreezing of water under nanoconfinement with the electric field. 

PMID- 25854256
TI  - Solid-liquid interface free energies of pure bcc metals and B2 phases.
AB  - The solid-liquid interface (SLI) free energy was determined from molecular
      dynamics (MD) simulation for several body centered cubic (bcc) metals and B2
      metallic compounds (space group: Pm3m; prototype: CsCl). In order to include a
      bcc metal with a low melting temperature in our study, a semi-empirical potential
      was developed for Na. Two additional synthetic "Na" potentials were also
      developed to explore the effect of liquid structure and latent heat on the SLI
      free energy. The obtained MD data were compared with the empirical Turnbull,
      Laird, and Ewing relations. All three relations are found to predict the general
      trend observed in the MD data for bcc metals obtained within the present study.
      However, only the Laird and Ewing relations are able to predict the trend
      obtained within the sequence of "Na" potentials. The Laird relation provides the
      best prediction for our MD data and other MD data for bcc metals taken from the
      literature. Overall, the Laird relation also agrees well with our B2 data but
      requires a proportionality constant that is substantially different from the bcc
      case. It also fails to explain a considerable difference between the SLI free
      energies of some B2 phases which have nearly the same melting temperature. In
      contrast, this difference is satisfactorily described by the Ewing relation.
      Moreover, the Ewing relation obtained from the bcc dataset also provides a
      reasonable description of the B2 data. 

PMID- 25854257
TI  - Interfacial free energy of the NaCl crystal-melt interface from capillary wave
      fluctuations.
AB  - In this work we study, by means of molecular dynamics simulations, the solid
      liquid interface of NaCl under coexistence conditions. By analysing capillary
      waves, we obtain the stiffness for different orientations of the solid and
      calculate the interfacial free energy by expanding the dependency of the
      interfacial free energy with the solid orientation in terms of cubic harmonics.
      We obtain an average value for the solid-fluid interfacial free energy of 89 +/-
      6 mN m(-1) that is consistent with previous results based on the measure of
      nucleation free energy barriers [Valeriani et al., J. Chem. Phys. 122, 194501
      (2005)]. We analyse the influence of the simulation setup on interfacial
      properties and find that facets prepared as an elongated rectangular stripe give
      the same results as those prepared as squares for all cases but the 111 face. For
      some crystal orientations, we observe at small wave-vectors a behaviour not
      consistent with capillary wave theory and show that this behavior does not depend
      on the simulation setup. 

PMID- 25854258
TI  - The impact of the competitive adsorption of ions at surface sites on surface free
      energies and surface forces.
AB  - The relationship between surface charge and surface potential at the solid-liquid
      interface is often determined by a charge regulation process, the chemisorption
      of a potential determining ion such as H(+). A subtle ion-specific effect can be
      observed when other ions compete with the primary potential determining ion to
      bind to a surface site. Site competition may involve alternative ions competing
      for a first binding site, e.g., metals ions competing with H(+) to bind to a
      negatively charged oxide or carboxyl site. Second-binding sites with site
      competition may also be found, including amphoteric OH2 (+) sites, or anion
      binding to amine groups. In this work, a general theoretical model is developed
      to describe the competitive adsorption of ions at surface sites. Applied to the
      calculation of forces, the theory predicts a 20% increase in repulsion between
      titania surfaces in 1 mM NaCl, and a 25% reduction in repulsion between silica
      surfaces in 0.1M NaCl compared to calculations neglecting ion site competition. 

PMID- 25854259
TI  - Lattice cluster theory for dense, thin polymer films.
AB  - While the application of the lattice cluster theory (LCT) to study the
      miscibility of polymer blends has greatly expanded our understanding of the
      monomer scale molecular details influencing miscibility, the corresponding theory
      for inhomogeneous systems has not yet emerged because of considerable technical
      difficulties and much greater complexity. Here, we present a general formulation
      enabling the extension of the LCT to describe the thermodynamic properties of
      dense, thin polymer films using a high dimension, high temperature expansion.
      Whereas the leading order of the LCT for bulk polymer systems is essentially
      simple Flory-Huggins theory, the highly non-trivial leading order inhomogeneous
      LCT (ILCT) for a film with L layers already involves the numerical solution of
      3(L - 1) coupled, highly nonlinear equations for the various density profiles in
      the film. The new theory incorporates the essential "transport" constraints of
      Helfand and focuses on the strict imposition of excluded volume constraints,
      appropriate to dense polymer systems, rather than the maintenance of chain
      connectivity as appropriate for lower densities and as implemented in self
      consistent theories of polymer adsorption at interfaces. The ILCT is illustrated
      by presenting examples of the computed profiles of the density, the parallel and
      perpendicular bonds, and the chain ends for free standing and supported films as
      a function of average film density, chain length, temperature, interaction with
      support, and chain stiffness. The results generally agree with expected general
      trends. 

PMID- 25854260
TI  - Dynamic heterogeneity in the folding/unfolding transitions of FiP35.
AB  - Molecular dynamics simulations have become an important tool in studying protein
      dynamics over the last few decades. Atomistic simulations on the order of micro-
      to milliseconds are becoming feasible and are used to study the state-of-the-art
      experiments in atomistic detail. Yet, analyzing the high-dimensional-long
      temporal trajectory data is still a challenging task and sometimes leads to
      contradictory results depending on the analyses. To reveal the dynamic aspect of
      the trajectory, here we propose a simple approach which uses a time correlation
      function matrix and apply to the folding/unfolding trajectory of FiP35 WW domain
      [Shaw et al., Science 330, 341 (2010)]. The approach successfully characterizes
      the slowest mode corresponding to the folding/unfolding transitions and
      determines the free energy barrier indicating that FiP35 is not an incipient
      downhill folder. The transition dynamics analysis further reveals that the
      folding/unfolding transition is highly heterogeneous, e.g., the transition path
      time varies by ~100 fold. We identify two misfolded states and show that the
      dynamic heterogeneity in the folding/unfolding transitions originates from the
      trajectory being trapped in the misfolded and half-folded intermediate states
      rather than the diffusion driven by a thermal noise. The current results help
      reconcile the conflicting interpretations of the folding mechanism and highlight
      the complexity in the folding dynamics. This further motivates the need to
      understand the transition dynamics beyond a simple free energy picture using
      simulations and single-molecule experiments. 

PMID- 25854261
TI  - Comment on "Frequency-domain stimulated and spontaneous light emission signals at
      molecular junctions" [J. Chem. Phys. 141, 074107 (2014)].

PMID- 25854262
TI  - Response to "Comment on 'Frequency-domain stimulated and spontaneous light
      emission signals at molecular junctions'" [J. Chem. Phys. 142, 137101 (2015)].

PMID- 25854263
TI  - Imaging team of the year.

PMID- 25854264
TI  - Early pregnancy maternal and fetal angiogenic factors and fetal and childhood
      growth: the Generation R Study.
AB  - STUDY QUESTION: What are the effects of maternal and fetal soluble fms-like
      tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF) concentrations on
      fetal and childhood growth patterns? SUMMARY ANSWER: An angiogenic profile that
      is characterized by both low early pregnancy maternal sFlt-1 and PlGF
      concentrations and higher sFlt-1 concentrations, lower PlGF concentrations or a
      higher sFlt-1:PlGF ratio in umbilical cord blood is associated with a reduced
      fetal and childhood growth. WHAT IS KNOWN ALREADY: An imbalance in maternal and
      fetal sFlt-1 and PlGF concentrations has been suggested to affect pregnancy
      outcomes. However, their effects on longitudinal fetal and childhood growth
      remain largely unknown. STUDY DESIGN, SIZE, DURATION: This study was performed in
      5980 mothers and 4108 of their children, participating in the Generation R Study;
      a population-based prospective cohort study from fetal life onwards in Rotterdam,
      the Netherlands (2001-2005). PARTICIPANTS/MATERIALS, SETTING, METHODS: Blood
      samples were obtained from mothers in early and mid-pregnancy and from the
      umbilical vein at delivery. Fetal and childhood growth characteristics (weight
      and length) were measured repeatedly by ultrasound and physical examinations
      until the age of 6 years. We assessed the associations of maternal and fetal
      angiogenic factors with fetal and childhood growth using repeated measurement
      regression models. Logistic regression models were used to determine associations
      between angiogenic factors and small for gestational age at birth (SGA). MAIN
      RESULTS AND THE ROLE OF CHANCE: Compared with early pregnancy maternal sFlt-1
      concentrations in the lowest quintile, early pregnancy maternal sFlt-1
      concentrations in the highest quintile were associated with a higher fetal weight
      growth resulting in a higher birthweight (difference in birthweight 0.33 standard
      deviation score (SDS); 95% Confidence Interval (CI) 0.25-0.41), a lower risk of
      SGA (Odds Ratio (OR) 0.36; 95% CI 0.27-0.48) and a subsequent higher weight
      growth until the age of 6 years. Early pregnancy maternal PlGF concentrations in
      the lowest quintile were associated with a reduced weight growth pattern
      resulting in a smaller birthweight (difference in birthweight -0.34 SDS; 95% CI 
      0.44, -0.25), an increased risk of SGA (OR 3.48; 95% CI 2.39-5.08) and a lower
      weight growth throughout childhood. An early pregnancy maternal sFlt-1:PlGF ratio
      in the highest quintile was associated with a higher fetal weight growth pattern
      from 30 weeks onwards, resulting in a higher weight at birth (difference in
      birthweight 0.09 SDS; P-value <0.05), which remained present until the age of 2
      years. Newborns with higher umbilical cord sFlt-1 concentrations, lower PlGF
      concentrations or a higher sFlt-1:PlGF ratio showed a lower fetal and childhood
      weight growth from 30 weeks gestation onwards until the age of 6 years (P-value
      <0.05). Similar patterns were observed in relation to fetal and childhood length
      growth. LIMITATIONS, REASONS FOR CAUTION: The study is an observational study.
      Therefore, no causal relationships can be established. WIDER IMPLICATIONS OF THE
      FINDINGS: Both a maternal and fetal angiogenic imbalance may affect fetal and
      childhood growth. Changes in angiogenic profiles may be involved in the pathways
      linking fetal growth restriction with the long-term risk of vascular disease in
      adulthood. STUDY FUNDING/COMPETING INTERESTS: The first phase of the Generation R
      Study is made possible by financial support from The Erasmus Medical Centre,
      Rotterdam, the Erasmus University Rotterdam, and the Netherlands Organization for
      Health Research and Development (ZonMw 21000074). V.W.V.J. received additional
      grants from the Netherlands Organization for Health Research and Development
      (ZonMw VIDI). M.I.B.-B. is financially supported by the Bo Hjelt foundation
      (grant 2009). The authors have no competing interests.

PMID- 25854265
TI  - Does living longer in good health facilitate longer working lives? The
      relationship between disability and working lives.
AB  - BACKGROUND: Improvements in life expectancy have fuelled debates about the
      statutory retirement age in many European countries. This article contributes to
      this debate by investigating how changes in disability may influence both
      employment outcomes and disability-free life expectancy. METHODS: We used data
      from the European Community Household Panel to estimate the impact of disability
      incidence on labour supply by country using propensity score techniques. In a
      second step, we translated the estimated effects of disability incidence into
      effects on working life expectancy as well as disability-free life expectancy
      using multi-state life tables. RESULTS: Results from the matching analysis show
      that individuals who become disabled are more likely to leave the labour market.
      However, the size of the effect is much weaker than a simple descriptive analysis
      suggests and varies by country. A 10% decrease in disability incidence results in
      increases in disability-free life expectancy and working life expectancy of
      respectively 0.6 and 0.07 years on average. CONCLUSION: A large part of the
      differences in employment between disabled and non-disabled individuals is not
      due to a causal effect of disability on employment. Policies that reduce
      disability incidence increase disability-free life expectancy but have only a
      limited impact on working life expectancy.

PMID- 25854267
TI  - Incorporating Peplau's Theory of Interpersonal Relations to Promote Holistic
      Communication Between Older Adults and Nursing Students.
AB  - With the increased life expectancy, older adults will interact with multiple
      health care providers to manage acute and chronic conditions. These interactions
      include nursing students who use various health care settings to meet the
      clinical practicum requirements of their programs. Nursing faculty are charged
      with facilitating students' learning throughout the program from basic human
      needs, to holistic communication, to advanced medical surgical concepts. Despite
      educating students on holistic communication, there remains a lack of a reliable
      framework to undertake the task of teaching holistic communication skills.
      Nursing students preparing to function as licensed practitioners need to develop
      appropriate knowledge to holistically care for older adults. The purpose of this
      article is to examine Hildegard Peplau's interpersonal relations theory as a
      framework to assist nursing students to understand holistic communication skills
      during their encounters with older adults. Peplau's theory provides nursing a
      useful set of three interlocking and oftentimes overlapping working phases for
      nurses' interaction with patients in the form of the nurse-patient relationship.
      Nursing education could adopt the three phases of Peplau's interpersonal
      relations theory to educate students on holistically communicating with older
      adults. 

PMID- 25854266
TI  - Osteoprotegerin and sclerostin in chronic kidney disease prior to dialysis:
      potential partners in vascular calcifications.
AB  - BACKGROUND: Osteoprotegerin (OPG), sclerostin and DKK1 constitute opposite bone
      turnover inhibitors, OPG inhibiting osteoclastogenesis while sclerostin and DKK1
      exerting their inhibitory effects on osteoblastogenesis. Both proteins have been
      recognized as strong risk factors of vascular calcifications in non-dialysis
      chronic kidney disease (ND-CKD) patients. The aim of this study was to
      investigate the relationships between these inhibitors and coronary artery
      calcifications (CAC) in this population. METHODS: A total of 241 ND-CKD patients
      [143 males; 69.0 (25.0-95.0) years; median estimated glomerular filtration rate
      using CKD-EPI 35.1 (6.7-120.1) mL/min/1.73 m(2)] were enrolled in this cross
      sectional study. All underwent chest multidetector computed tomography for CAC
      scoring. OPG, sclerostin, DKK1 and mineral metabolism markers including PTH and
      bone alkaline phosphatase were measured. Logistic regression analyses were used
      to study the relationships between CAC and these markers. RESULTS: Decline in
      renal function was associated with a significant increase in OPG and sclerostin
      while a slight but significant decrease in DKK1 was observed. The main crude
      associations with presence of CAC were a high level of OPG [OR = 2.55 95%
      confidence interval (95% CI) (1.35-4.82) for a level ranging from 6.26 to 9.15
      pmol/L and OR = 5.74 95% CI (2.87-11.5) for a level >=9.15 pmol/L; P < 0.0001]
      and a high level of sclerostin [OR = 2.64 95% CI (1.39-5.00) for a level ranging
      from 0.748 to 1.139 ng/mL and OR = 3.78 95% CI (1.96-7.31) for a level >=1.139
      ng/mL; P = 0.0002]. A logistic regression model clearly showed that the risk to
      present CAC was significantly increased when both OPG (>=6.26 pmol/L) and
      sclerostin (>=0.748 ng/mL) levels were high [crude model: OR = 11.47 95% CI (4.54
      29.0); P < 0.0001; model adjusted for age, gender, diabetes, body mass index and
      smoking habits: OR = 5.69 95% CI (1.76-18.4); P = 0.02]. No association between
      DKK1 and presence of CAC was observed. CONCLUSIONS: Our results strongly suggest
      that bone turnover inhibitors, OPG and sclerostin, are independently associated
      with CAC with potential additive effects in ND-CKD patients.

PMID- 25854269
TI  - Life and mental health of medical students after the Great East Japan Earthquake.
AB  - Students of the Tohoku University School of Medicine experienced the Great East
      Japan Earthquake on March 11, 2011. We conducted a series of surveys to examine
      the relationships among their experiences and activities on the day of the
      earthquake, their physical, mental, and economic problems following the disaster,
      and how their problems changed over time. The initial survey was performed in
      April 2011, with three follow-up surveys in July 2011, February 2012, and April
      2013. The initial survey focused on students' experiences and living conditions
      during the disaster, which contained questions on their locations and
      circumstances, family circumstances, lives after the earthquake, voluntary works,
      physical or mental health problems, and desire for counseling. The follow-up
      surveys included new items regarding their circumstances, changes in their health
      problems, and their desire for economic assistance. Students who answered the
      first survey to the 4th one, with response rates in the following bracket, were
      as follows: 472 (28.0%), 640 (29.9%), 681 (36.0%), and 678 (39.0%), respectively.
      Six months after the earthquake, about 20% having experienced physical and/or
      mental problems. Although there was a trend toward a reduction in suffering and
      health problems over time, some students' conditions remained unchanged or
      worsened. It is notable that students who had participated in voluntary
      activities, despite their own suffering of harm and distress, were identified as
      the group that required the closest attention. Our present results can be applied
      to appropriate supports for students in future large-scale disasters. 

PMID- 25854268
TI  - Vascular calcifications on hand radiographs in rheumatoid arthritis and
      associations with autoantibodies, cardiovascular risk factors and mortality.
AB  - OBJECTIVE: To examine whether vascular calcifications on hand films in RA might
      aid in determining mortality risk. METHODS: Hand radiographs from 906 RA patients
      were scored as positive or negative for vascular calcifications. Patient
      characteristics associated with vascular calcifications were assessed using
      multivariable logistic regression, and associations with mortality were examined
      using Cox proportional hazards regression. Cytokines and multiplex ACPA were
      measured in both groups. RESULTS: A total of 99 patients (11%) demonstrated
      radiographic vascular calcifications. Factors independently associated with
      vascular calcifications included diabetes [odds ratio (OR) 2.85; 95% CI 1.43,
      5.66], cardiovascular disease at enrolment (OR 2.48; 95% CI 1.01, 6.09),
      prednisone use (OR 1.90; 95% CI 1.25, 2.91), current smoking (OR 0.06; 95% CI
      0.01, 0.23) and former smoking (OR 0.36; 95% CI 0.27, 0.48) vs never smoking. In
      cytokine and ACPA subtype analysis, IL-4 and anti-citrullinated apolipoprotein E
      were significantly increased in patients with vascular calcifications in fully
      adjusted multivariable models. After multivariable adjustment, vascular
      calcifications were associated with an increase in all-cause mortality (hazard
      ratio 1.41; 95% CI 1.12, 1.78; P = 0.004). CONCLUSION: Vascular calcifications on
      hand radiographs were independently associated with increased all-cause mortality
      in RA. Mechanisms underpinning the associations of IL-4 and select ACPA with
      vascular calcifications and their utility as biomarkers predictive of
      cardiovascular disease risk in RA merit further study.

PMID- 25854270
TI  - Tissue inhibitor of metalloproteinase-1 is responsible for residual pleural
      thickening in pleural tuberculosis.
AB  - Residual pleural thickening (RPT) is the most frequent complication associated
      with pleural tuberculosis, and may occur even after successful anti-tuberculosis
      medications. Matrix metalloproteinases (MMPs) are zinc-dependent proteinases
      capable of degrading all components of the extracellular matrix. The proteolytic
      action of MMPs may be involved in the pathogenesis of tuberculosis. MMP-9,
      secreted by monocytes and lymphocyte, may lead to long-term fibrosis. The aim of
      the present study was to determine whether MMP-2 and/or MMP-9 and their specific
      inhibitors, tissue inhibitors of metalloproteinase 1 (TIMP-1) and TIMP-2, could
      be used to predict RPT. This retrospective study enrolled 52 patients diagnosed
      with pleural tuberculosis. Levels of MMP-2, MMP-9, TIMP-1, and TIM-2 were
      determined in the pleural fluid by ELISA. The RPT was measured on chest X-ray at
      the completion of treatment and the final follow-up. The average periods of anti
      tuberculosis medication and the follow-up after completion of treatment were 6.7
      and 7.6 months, respectively. MMP-2 or MMP-9 levels had no significant
      correlation to RPT. The patients with RPT > 2 mm at the completion of anti
      tuberculosis medication and the final follow-up had higher TIMP-1 levels (p =
      0.00 and p = 0.001, respectively). However, patients with RPT > 2 mm at the
      completion of anti-tuberculosis medication had lower TIMP-2 levels (p = 0.005).
      In a logistic regression model, elevated TIMP-1 levels at the completion of anti
      tuberculosis medications were associated with RPT. In conclusion, higher TIMP-1
      levels are responsible for the development of RPT and may be helpful for
      predicting RPT in pleural tuberculosis. 

PMID- 25854271
TI  - Effects of metabolic syndrome on language functions in aging.
AB  - This study explored effects of the metabolic syndrome (MetS) on language in
      aging. MetS is a constellation of five vascular and metabolic risk factors
      associated with the development of chronic diseases and increased risk of
      mortality, as well as brain and cognitive impairments. We tested 281 English
      speaking older adults aged 55-84, free of stroke and dementia. Presence of MetS
      was based on the harmonized criteria (Alberti et al., 2009). Language performance
      was assessed by measures of accuracy and reaction time on two tasks of lexical
      retrieval and two tasks of sentence processing. Regression analyses, adjusted for
      age, education, gender, diabetes, hypertension, and heart disease, demonstrated
      that participants with MetS had significantly lower accuracy on measures of
      lexical retrieval (action naming) and sentence processing (embedded sentences,
      both subject and object relative clauses). Reaction time was slightly faster on
      the test of embedded sentences among those with MetS. MetS adversely affects the
      language performance of older adults, impairing accuracy of both lexical
      retrieval and sentence processing. This finding reinforces and extends results of
      earlier research documenting the negative influence of potentially treatable
      medical conditions (diabetes, hypertension) on language performance in aging. The
      unanticipated finding that persons with MetS were faster in processing embedded
      sentences may represent an impairment of timing functions among older individuals
      with MetS.

PMID- 25854275
TI  - Electrophoretic deposition and characterization of nanocomposites and
      nanoparticles on magnesium substrates.
AB  - This study introduces a triphasic design of biodegradable materials composed of
      nanophase hydroxyapatite (nHA), poly(lactic-co-glycolic acid) (PLGA), and
      magnesium (Mg) substrates for musculoskeletal implant applications. Specifically,
      nHA_PLGA composites and nHA nanoparticles were synthesized, deposited on three
      dimensional Mg substrates using electrophoretic deposition (EPD), and
      characterized. The three components involved, that is, nHA, PLGA, and Mg are all
      biodegradable in the human body, thus promising for biodegradable implant and
      device applications. Mg and its alloys are attractive for musculoskeletal implant
      applications due to their comparable modulus and strength to cortical bone.
      Controlling the interface of Mg with the biological environment, however, is the
      key challenge that currently limits this biodegradable metal for broad
      applications in medical implants. This article particularly focuses on creating
      nanostructured interface between the biodegradable Mg and surrounding tissue for
      the dual purposes of (1) mediating the degradation of the Mg-based substrates and
      (2) potentially enhancing osteointegration. Nanophase hydroxyapatite (nHA) is an
      excellent candidate as a coating material due to its osteoconductivity, while the
      polymer phase promotes interfacial adhesion between the nHA and Mg. Moreover, the
      degradation products of PLGA and Mg neutralize each other. Surface
      characterization showed successful deposition of nHA_PLGA composite microspheres
      and nHA nanoparticles on Mg substrates using EPD. Mg substrates coated with
      nHA_PLGA composites showed greater adhesion strength when compared with nHA
      coating, and slower corrosion rate than nHA coated Mg and non-coated Mg. The
      triphasic composites of nHA, PLGA and Mg are promising as the next-generation
      biodegradable materials for medical applications. 

PMID- 25854276
TI  - Two strikes: race and the disciplining of young students.
AB  - There are large racial disparities in school discipline in the United States,
      which, for Black students, not only contribute to school failure but also can lay
      a path toward incarceration. Although the disparities have been well documented,
      the psychological mechanisms underlying them are unclear. In two experiments, we
      tested the hypothesis that such disparities are, in part, driven by racial
      stereotypes that can lead teachers to escalate their negative responses to Black
      students over the course of multiple interpersonal (e.g., teacher-to-student)
      encounters. More generally, we argue that race not only can influence how
      perceivers interpret a specific behavior, but also can enhance perceivers'
      detection of behavioral patterns across time. Finally, we discuss the theoretical
      and practical benefits of employing this novel approach to stereotyping across a
      range of real-world settings. 

PMID- 25854277
TI  - Did Shakespeare write double falsehood? Identifying individuals by creating
      psychological signatures with text analysis.
AB  - More than 100 years after Shakespeare's death, Lewis Theobald published Double
      Falsehood, a play supposedly sourced from a lost play by Shakespeare and John
      Fletcher. Since its release, scholars have attempted to determine its true
      authorship. Using new approaches to language and psychological analysis, we
      examined Double Falsehood and the works of Theobald, Shakespeare, and Fletcher.
      Specifically, we created a psychological signature from each author's language
      and statistically compared the features of each signature with those of Double
      Falsehood's signature. Multiple analytic approaches converged in suggesting that
      Double Falsehood's psychological style and content architecture predominantly
      resemble those of Shakespeare, showing some similarity with Fletcher's signature
      and only traces of Theobald's. Closer inspection revealed that Shakespeare's
      influence is most apparent early in the play, whereas Fletcher's is most apparent
      in later acts. Double Falsehood has a psychological signature consistent with
      that expected to be present in the long-lost play The History of Cardenio,
      cowritten by Shakespeare and Fletcher. 

PMID- 25854272
TI  - Time estimation and production in HIV-associated neurocognitive disorders (HAND).
AB  - The ability to accurately perceive the passage of time relies on several
      neurocognitive abilities, including attention, memory, and executive functions,
      which are domains commonly affected in persons living with HIV disease. The
      current study examined time estimation and production and their neurocognitive
      correlates in a sample of 53 HIV+ individuals with HIV-associated neurocognitive
      disorders (HAND), 120 HIV+ individuals without HAND, and 113 HIV- individuals.
      Results revealed a moderate main effect of HAND on time estimation and a trend
      level effect on time production, but no interaction between HAND and time
      interval duration. Correlational analyses revealed that time estimation in the
      HIV+ group was associated with attention, episodic memory and time-based
      prospective memory. Findings indicate that individuals with HAND evidence
      deficits in time interval judgment suggestive of failures in basic attentional
      and memory processes.

PMID- 25854278
TI  - Cattle veterinarians' awareness and understanding of biosecurity.

PMID- 25854279
TI  - Evidence of members of the Chlamydiales in bovine abortions in England and Wales.

PMID- 25854280
TI  - Anatomical study of surgical approaches for minimally invasive transoral
      thyroidectomy: eMIT and TOPP.
AB  - OBJECTIVE: Anatomical study of surgical approaches of endoscopic minimally
      invasive thyroidectomy (eMIT) and transoral partial parathyroidectomy (TOPP) was
      conducted to evaluate their safety and feasibility. MATERIAL AND METHODS: After
      performing an eMIT- and TOPP-procedure on fresh frozen human cadavers, a layer-by
      layer dissection of the floor of the mouth and the anterior cervical region was
      carried out in five specimens. The blood vessels, nerves and muscles related to
      the surgical approach were exposed. RESULTS: The anterior region of the neck can
      be reached through the midline of the mouth floor and the suprahyoid muscles. No
      important nerves and vessels were found in the approach of eMIT. TOPP set up the
      space at the dorsal side of the thyroid gland and adjacent to the trachea. The
      hypoglossal nerve and the lingual nerve as well as their accompanying blood
      vessels were anatomically related to the approach and could be injured during the
      procedure. The surgical space is much limited in TOPP (<20 mm in diameter) and
      current surgical instruments still did not match the requirement of this
      technique. CONCLUSIONS: This study demonstrated that the transoral approach of
      eMIT is anatomically safer and more feasible than that of TOPP.

PMID- 25854281
TI  - Prevalence of palmar fibromatosis with and without contracture in asymptomatic
      patients.
AB  - BACKGROUND: This retrospective study documents the proportion of hand clinic
      patients presenting with palmar fibromatosis with and without contracture.
      METHODS: All "new" patients >18 years presenting to a single surgeon's hand
      clinic over a 16-month period were included, and information was abstracted from
      chart review regarding patient demographics, reason for presentation, presence or
      absence of palmar fibromatosis, contracture, and prior known diagnosis of
      Dupuytren's disease. The percentage of asymptomatic patients with palmar
      fibromatosis was calculated. RESULTS: Of 827 patients, 306 had palmar
      fibromatosis. Among all patients, 33% of male and 40% of female patients had
      palmar fibromatosis. Only 8% had contractures, while 92% had palmar fibromatosis
      without contracture. Among those who had contractures, 81% presented with a
      primary complaint of Dupuytren's disease (symptomatic contracture). Prevalence of
      palmar fibromatosis increased with increasing age. CONCLUSION: The findings
      demonstrate that Dupuytren's palmar fibromatosis is common and often present
      without overt contractures.

PMID- 25854282
TI  - Effect of varied recovery interventions on markers of psychophysiological stress
      in professional rugby union.
AB  - Rugby union is a physical demanding sport that requires optimum recovery between
      games to maintain performance levels. Analysis of four unique biochemical markers
      of stress is measured here to determine which recovery strategy currently in use
      by a professional team provides the necessary requirements for sustained
      performance. Urine and saliva samples were collected from 37 professional rugby
      players before, immediately after and 36 hours after five home games, and
      analysed by enzyme linked immunosorbent assay and high performance liquid
      chromatography for urinary myoglobin, total neopterin (NP; NP + 7,8
      dihydroneopterin), salivary cortisol and immunoglobulin A. Subjects completed a
      cold water immersion (CWI) or pool session (PS), donned compression garments,
      consumed protein and carbohydrate food and fluid, and slept for 8 hours post
      game. The following day subjects choose from one or a combination of CWI, PS or
      active recovery/stretching to complete. There was no difference between the
      recovery protocols for cortisol, total NP, immunoglobulin A concentration or
      myoglobin at 36 hours post-game. Immunoglobulin A secretion rate significantly
      increased above pre-game levels at 36 hours post-game for all protocols; however,
      protocol three did not increase as much (p = 0.038). Total NP was also
      significantly increased above pre-game levels at 36 hours post-game for all
      protocols. This study provides evidence that the immediate post-game recovery
      intervention following a game of professional rugby union may be the most
      important aspect of psychophysiological player recovery, irrespective of the
      "next-day" intervention. The concentrations of total NP and immunoglobulin A
      suggest these professional rugby players are still in a state of recovery 36
      hours post-game. 

PMID- 25854283
TI  - Characterization of a New DGKE Intronic Mutation in Genetically Unsolved Cases of
      Familial Atypical Hemolytic Uremic Syndrome.
AB  - BACKGROUND AND OBJECTIVES: Genetic and acquired abnormalities causing
      dysregulation of the complement alternative pathway contribute to atypical
      hemolytic uremic syndrome (aHUS), a rare disorder characterized by
      thrombocytopenia, nonimmune microangiopathic hemolytic anemia, and acute kidney
      failure. However, in a substantial proportion of patients the disease-associated
      alterations are still unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:
      Whole-exome and whole-genome sequencing were performed in two unrelated families
      with infantile recessive aHUS. Sequencing of cDNA from affected individuals was
      used to test for the presence of aberrant mRNA species. Expression of mutant
      diacylglycerol kinase epsilon (DGKE) protein was evaluated with western blotting.
      RESULTS: Whole-exome sequencing analysis with conventional variant filtering
      parameters did not reveal any obvious candidate mutation in the first family. The
      report of aHUS-associated mutations in DGKE, encoding DGKE, led to re-examination
      of the noncoding DGKE variants obtained from next-generation sequencing, allowing
      identification of a novel intronic DGKE mutation (c.888+40A>G) that segregated
      with disease. Sequencing of cDNA from affected individuals revealed aberrant
      forms of DGKE mRNA predicted to cause profound abnormalities in the protein
      catalytic site. By whole-genome sequencing, the same mutation was found in
      compound heterozygosity with a second nonsense DGKE mutation in all affected
      siblings of another unrelated family. Homozygous and compound heterozygous
      patients presented similar clinical features, including aHUS presentation in the
      first year of life, multiple relapsing episodes, and proteinuria, which are
      prototypical of DGKE-associated aHUS. CONCLUSIONS: This is the first report of a
      mutation located beyond the exon-intron boundaries in aHUS. Intronic mutations
      such as these are underreported because conventional filtering parameters used to
      process next-generation sequencing data routinely exclude these regions from
      downstream analyses in both research and clinical settings. The results suggest
      that analysis of noncoding regions of aHUS-associated genes coupled with mRNA
      sequencing might provide a tool to explain genetically unsolved aHUS cases.

PMID- 25854284
TI  - A phase I/II study of oral clofarabine plus low-dose cytarabine in previously
      treated acute myeloid leukaemia and high-risk myelodysplastic syndrome patients
      at least 60 years of age.
AB  - Outcomes for older adults with acute myeloid leukaemia (AML) and myelodysplastic
      syndrome (MDS) are generally poor, and new effective therapies are needed. We
      investigated oral clofarabine combined with low-dose cytarabine (LDAC) in
      patients aged 60 years and above with relapsed or refractory AML or high-risk MDS
      in a phase I/II trial. A 3 + 3 dose escalation of oral clofarabine was followed
      by a phase II expansion with the aim of obtaining a complete response (CR) rate
      >=30%. We identified 20 mg/d for 5 d as the maximum tolerated dose (MTD) of oral
      clofarabine. A total of 35 patients, with a median age of 72 years, were treated.
      Of 26 patients enrolled at the MTD, 4 had treatment-related grade 3-4 non
      haematological toxicities, but none died within 28 d. The observed CR rate and
      median survival were 34% [95% confidence interval (CI), 18-50%] and 6.8 months
      overall and 38% [95% CI, 19-57%] and 7.2 months at the MTD. The median disease
      free survival was 7.4 months. Fifty-two percent (23/44) of cycles administered at
      the MTD were done without hospital admission. This combination of oral
      clofarabine and LDAC demonstrated efficacy with a CR rate of >30% and acceptable
      toxicity in older patients.

PMID- 25854285
TI  - Blood markers of oxidative stress predict weaning failure from mechanical
      ventilation.
AB  - Patients undergoing mechanical ventilation (MV) often experience respiratory
      muscle dysfunction, which complicates the weaning process. There is no simple
      means to predict or diagnose respiratory muscle dysfunction because diagnosis
      depends on measurements in muscle diaphragmatic fibre. As oxidative stress is a
      key mechanism contributing to MV-induced respiratory muscle dysfunction, the aim
      of this study was to determine if differences in blood measures of oxidative
      stress in patients who had success and failure in a spontaneous breathing trial
      (SBT) could be used to predict the outcome of MV. This was a prospective analysis
      of MV-dependent patients (>=72 hrs; n = 34) undergoing a standard weaning
      protocol. Clinical, laboratory and oxidative stress analyses were performed.
      Measurements were made on blood samples taken at three time-points: immediately
      before the trial, 30 min. into the trial in weaning success (WS) patients, or
      immediately before return to MV in weaning failure (WF) patients, and 6 hrs after
      the trial. We found that blood measures of oxidative stress distinguished
      patients who would experience WF from patients who would experience WS. Before
      SBT, WF patients presented higher oxidative damage in lipids and higher
      antioxidant levels and decreased nitric oxide concentrations. The observed
      differences in measures between WF and WS patients persisted throughout and after
      the weaning trial. In conclusion, WF may be predicted based on higher
      malondialdehyde, higher vitamin C and lower nitric oxide concentration in plasma.

PMID- 25854287
TI  - The residual risk of transfusion-transmitted cytomegalovirus infection associated
      with leucodepleted blood components.
AB  - BACKGROUND AND OBJECTIVES: Cytomegalovirus poses a risk to transfusion safety as
      its transmission to an immunocompromised recipient may lead to significant
      clinical sequelae. Once infection is established, it is lifelong and generally
      asymptomatic. Strategies to reduce the risk of transfusion-transmitted CMV (TT
      CMV) include donor serological testing and blood component leucodepletion to
      deplete the transmissible reservoir. We estimate the residual risk for non-CMV
      antibody screened, leucodepleted (LD-only) fresh blood components. MATERIALS AND
      METHODS: We established an approach to estimate the risk of TT-CMV under various
      scenarios. We estimated the probability of an infectious component, for both red
      cells and platelets, as a function of the observed WBC filter failure rate and
      the probability that such a unit was also contaminated with infectious virus.
      RESULTS: Using this model, the estimated combined residual risk of LD-only red
      cell and platelet units was very low, 1 in 13 575 000 (95%CI:1 in 1 344 167 000-1
      in 1 730 000) as was the individual residual risk estimate for LD-only red cells,
      1 in 7 790 000 (95%CI: 1 in 771 307 000-1 in 993 000) and LD-only platelets,
      where a zero risk was estimated (95%CI: 0-1 in 1 074 000). CONCLUSION: We
      describe a novel approach to assess the residual risk of LD-only components. This
      can be applied generally using local data. Our risk estimate for LD-only blood
      components in Australia is below the threshold of 1 in 1 million, generally
      considered negligible. This provides a useful indicator of the relative safety of
      LD-only components to assist clinical decisions when serologically screened
      inventory is unavailable.

PMID- 25854286
TI  - Asthma control and cognitive function in a cohort of elderly adults.
AB  - OBJECTIVES: To determine whether poor asthma control is associated with cognitive
      impairment in a cohort of older, inner-city adults with asthma. DESIGN:
      Prospective observational cohort study. SETTING: Outpatient practices in New York
      City and Chicago. PARTICIPANTS: Individuals aged 60 and older with a physician
      diagnosis of asthma and without chronic obstructive pulmonary disease or a
      smoking history of 10 pack-years or more (N = 452). MEASUREMENTS: Cognitive
      assessments that included processing speed (pattern comparison, Trail-Making Test
      Part A), executive function (Trail-Making Test Part B), attention and working
      memory (letter number sequencing), immediate and delayed recall (Wechsler Memory
      Scale Story A), word fluency (animal naming), and global cognitive function (Mini
      Mental State Examination) were administered. Asthma control was measured using
      the Asthma Control Questionnaire (ACQ) and airway obstruction using spirometry as
      the predicted forced expiratory volume at 1 second (FEV1) of less than 70%.
      Cognitive measures were modeled in linear and logistic regression models
      controlling for age, race, education, English proficiency, and income. RESULTS:
      Participants had a mean age of 68; 41% had poor asthma control according to the
      ACQ, and 35% had FEV1 of less than 70%. Poor asthma control and FEV1 less than
      70% were significantly associated with all measures of cognitive function in
      univariate analyses, although these associations lost their statistical
      significance after adjusting for age, education, English proficiency, and other
      covariates. The same pattern was observed when the outcomes were below-normal
      performance on the cognitive measures based on normative data. CONCLUSION: Poor
      asthma control and airway obstruction are not associated with poor performance on
      various measures of cognitive function in older adults with asthma.

PMID- 25854288
TI  - Volaemic status and dyspepsia in end-stage renal disease patients.
AB  - AIM: Studies in animals show a relationship between extracellular volume and
      gastrointestinal motility. End-stage renal disease (ESRD) patients present fluid
      overload and frequent dyspeptic symptoms. We looked for an association between
      volaemic status and dyspepsia among ESRD patients undergoing haemodialysis (HD).
      METHODS: We studied 155 ESRD patients on HD. Their volaemic status was evaluated
      using bioimpedance analysis. Fluid overload (FO) in litres and relative fluid
      overload (rFO) in percentage were calculated. rFO > 15% was classified as
      hypervolaemia. Dyspepsia was assessed through the Porto Alegre Dyspeptic Symptoms
      Questionnaire (PADYQ). PADYQ scores equal to or greater than 6 classified
      patients as dyspeptic. Characteristics of patients with and without dyspepsia
      were compared. Pearson's test was used to test the correlation between continuous
      variables. Multivariate linear and logistic regressions were performed to test FO
      as predictor of dyspepsia score and the presence of dyspepsia. RESULTS: There
      were 64 (41.2%) patients with dyspepsia. Dyspeptics presented higher FO (2.5 +/-
      1.8 L vs 1.0 +/- 1.8 L; P < 0.001) and higher rFO (16 +/- 9.9% vs 4.8 +/- 12.0%;
      P < 0.001). Dyspepsia score was positively correlated with FO (r = 0.300; P <
      0.001) and with rFO (r = 0.256; P = 0.001). There were more patients with
      hypervolaemia among dyspeptics compared to non-dyspeptics (65.6% vs 17.6%; P <
      0.001). FO was an independent predictor of dyspepsia score (b = 1.036; P < 0.001)
      and the presence of dyspepsia (OR = 2.00, 95% CI = 1.55-2.50; P < 0.001).
      CONCLUSION: Hypervolaemia is associated with dyspepsia among ESRD patients on HD.

PMID- 25854289
TI  - Associations of glycated haemoglobin A1c and glycated albumin with subclinical
      atherosclerosis in middle-aged and elderly Chinese population with impaired
      glucose regulation.
AB  - The aim of this study was to investigate the correlations of glycated haemoglobin
      A1c (HbA1c) and glycated albumin (GA) with subclinical atherosclerosis in middle
      aged and elderly Chinese populations with impaired glucose regulation (IGR). In
      total, 640 subjects with IGR and no history of cardiovascular disease or carotid
      artery plaque were recruited for this study (256 men, 384 women; age range, 40-70
      years). The carotid intima-media thickness (C-IMT) measured by carotid
      ultrasonography was used as an indicator of subclinical atherosclerosis.
      Increased C-IMT was defined as >= 0.70 mm (upper quartile). HbA1c and GA were
      measured with high-performance liquid chromatography and enzymatic method,
      respectively. The average HbA1c and GA among all 640 subjects were 5.7 +/- 0.3%
      and 14.0 +/- 1.1%, respectively. HbA1c and GA were higher in subjects with
      increased C-IMT than in subjects with normal C-IMT (5.8 +/- 0.3% vs 5.7 +/- 0.3%
      and 14.2 +/- 1.0% vs 13.9 +/- 1.1%, respectively; both P < 0.01). Correlation
      analysis showed that both HbA1c and GA were positively correlated with C-IMT (r =
      0.135 and 0.112, respectively; both P < 0.01). Logistic regression analysis
      revealed that both HbA1c (odds ratio (OR), 2.630; 95% confidence interval (95%
      CI), 1.401-4.935; P = 0.003) and GA OR, 1.215; 95% CI, 1.008-1.466; P = 0.041)
      were independent risk factors for increased C-IMT. Both HbA1c and GA reflect the
      risk of subclinical atherosclerosis in middle-aged and elderly Chinese
      populations with IGR.

PMID- 25854290
TI  - Factor VIII products in haemophilia A: one size fits all?

PMID- 25854291
TI  - Differentiating between signs of intra-articular joint bleeding and chronic
      arthropathy in haemophilia: a narrative review of the literature.
AB  - INTRODUCTION: Elderly patients with haemophilia (PWH) suffer from both
      haemarthrosis and haemophilic arthropathy (HA). Diagnosis of haemarthrosis in PWH
      is currently based on clinical presentation. No diagnostic protocols or validated
      criteria are available to identify haemarthrosis or to differentiate
      haemarthrosis from HA. AIM: The aim of this study is to identify symptoms and
      signs that can be used to differentiate haemarthrosis from HA. METHODS: A
      narrative literature review was performed on symptoms associated with
      haemarthrosis and symptoms associated with HA. Additionally, literature on the
      diagnosis of haemarthrosis in patients without haemophilia, imaging techniques
      and biomarkers was searched. RESULTS: This review shows that there is no
      consensus about the symptoms associated with haemarthrosis and that there is
      limited literature about the symptoms associated with HA. Additionally, symptoms
      associated with haemarthrosis partly overlap with symptoms of HA, particularly
      those symptoms associated with flare-ups of HA. Due to the overlap in symptoms
      differentiating between these conditions is complex. Furthermore, differentiating
      based on imaging techniques or biomarkers causes practical difficulties.
      CONCLUSION: Despite the overlap in symptoms, differentiating between joint bleeds
      and flare-ups of HA based on clinical presentation still seems the most
      convenient and practical solution. Further research is necessary to identify
      specific symptoms that can be used to differentiate between the two conditions.

PMID- 25854292
TI  - Accelerating Improvement and Narrowing Gaps: Trends in Patients' Experiences with
      Hospital Care Reflected in HCAHPS Public Reporting.
AB  - OBJECTIVE: Measure HCAHPS improvement in hospitals participating in the second
      and fifth years of HCAHPS public reporting; determine whether change is greater
      for some hospital types. DATA: Surveys from 4,822,960 adult inpatients discharged
      July 2007-June 2008 or July 2010-June 2011 from 3,541 U.S. hospitals. STUDY
      DESIGN: Linear mixed-effect regression models with fixed effects for time,
      patient mix, and hospital characteristics (bedsize, ownership, Census division,
      teaching status, Critical Access status); random effects for hospitals and
      hospital-time interactions; fixed-effect interactions of hospital characteristics
      and patient characteristics (gender, health, education) with time predicted
      HCAHPS measures correcting for regression-to-the-mean biases. DATA COLLECTION
      METHODS: National probability sample of adult inpatients in any of four approved
      survey modes. PRINCIPAL FINDINGS: HCAHPS scores increased by 2.8 percentage
      points from 2008 to 2011 in the most positive response category. Among the middle
      95 percent of hospitals, changes ranged from a 5.1 percent decrease to a 10.2
      percent gain overall. The greatest improvement was in for-profit and larger (200
      or more beds) hospitals. CONCLUSIONS: Five years after HCAHPS public reporting
      began, meaningful improvement of patients' hospital care experiences continues,
      especially among initially low-scoring hospitals, reducing some gaps among
      hospitals.

PMID- 25854293
TI  - Mobile Phone and Tablet Apps to Support Young People's Management of Their
      Physical Long-Term Conditions: A Systematic Review Protocol.
AB  - BACKGROUND: The prevalence of long-term or chronic conditions that limit activity
      and reduce quality of life in young people aged 10-24 years is rising. This group
      has distinct health care needs and requires tailored support strategies to
      facilitate increasing personal responsibility for the management of their
      condition wherever possible, as they mature. Mobile phone and tablet mobile
      technologies featuring software program apps are already well used by young
      people for social networking or gaming. They have also been utilized in health
      care to support personal condition management, using condition-specific and
      patient-tailored software. Such apps have much potential, and there is an
      emerging body of literature on their use in a health context making this review
      timely. OBJECTIVE: The objective of this paper is to develop a systematic review
      protocol focused on identifying and assessing the effectiveness of mobile phone
      and tablet apps that support young people's management of their chronic
      conditions. METHODS: The search strategy will include a combination of
      standardized indexed search terms and free-text terms related to the key concepts
      of young people; long-term conditions and mobile technology. Peer-reviewed
      journal articles published from 2003 that meet the inclusion and exclusion
      criteria will be identified through searching the generated hits from 5
      bibliographical databases. Two independent reviewers will screen the titles and
      abstracts to determine which articles focus on testing interventions identified
      as a mobile phone or tablet apps, and that have been designed and delivered to
      support the management of long-term conditions in young people aged 10-24 years.
      Data extraction and quality assessment tools will be used to facilitate
      consistent analysis and synthesis. It is anticipated that several studies will
      meet the selection criteria but that these are likely to be heterogeneous in
      terms of study design, reported outcomes, follow-up times, participants' age, and
      health condition. Sub-group analyses will be undertaken and where possible meta
      analyses will take place. RESULTS: This review will synthesize available
      knowledge surrounding tablet and mobile phone apps that support management of
      long term physical health conditions in young people. The findings will be
      synthesized to determine which elements of the technologies were most effective
      for this population. CONCLUSIONS: This systematic review aims to synthesize
      existing literature in order to generate findings that will facilitate the
      development of an app intervention. The review will form the first phase of
      development and evaluation of a complex intervention as recommended by the United
      Kingdom Medical Research Council. The knowledge gained from the review will be
      verified in subsequent phases, which will include primary qualitative work with
      health professionals and young people with long term conditions as research
      participants. Young people living with long-term conditions will be involved as
      co-researchers and consumer advisors in all subsequent phases to develop and
      evaluate an app to support the management of long-term physical health
      conditions. TRIAL REGISTRATION: PROSPERO International prospective register of
      systematic reviews: CRD42014015418;
      http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42014015418#.VRqCpTpn
      8E (Archived by Webcite at http://www.webcitation.org/6XREcWqQY).

PMID- 25854294
TI  - Burden of stroke in Italy: an economic model highlights savings arising from
      reduced disability following thrombolysis.
AB  - BACKGROUND: The consequences of stroke must be assessed not only in terms of
      incidence and mortality rates, but also in terms of disability, which may persist
      long after the acute phase. Thrombolysis, if timely administered, can effectively
      reduce post-stroke disability. AIMS: The economic model presented herein aims to
      evaluate, in eligible patients, the effects of alteplase on post-stroke
      disability and related costs over three-years. METHODS: The economic analysis was
      developed on the basis of four key components: clinical outcomes from
      international trials, economic consequences extracted from cost of illness
      studies, regulatory data from national and international agencies, and national
      epidemiological data. A population-level model estimated the difference in
      disability costs between patients treated with standard care versus those
      receiving thrombolytic therapy within 4*5 h of acute ischemic stroke. The
      analysis covered 36 months from discharge. RESULTS: Reduced costs related to post
      stroke disability were observed in treated patients compared with those receiving
      standard care (control). The overall savings were ?2330*15 per average patient:
      ?1445*81 during the first 18 months, ?362*25 between 18 and 24 months, and
      ?522*09 in the 24-36 months period. The overall savings on 3174 Italian treated
      patients in 2013 were ?7 395 907 over three-years. CONCLUSION: Our study reveals
      that performing thrombolytic therapy in eligible patients improves economic
      outcomes compared with patients receiving standard care. This model is useful for
      decision makers, both within and outside of the Italian national context, as a
      tool to assess the cost-effectiveness of thrombolysis in both short- and long
      term period.

PMID- 25854295
TI  - Received social support and exercising: An intervention study to test the
      enabling hypothesis.
AB  - OBJECTIVES: Received social support is considered important for health-enhancing
      exercise participation. The enabling hypothesis of social support suggests an
      indirect association of social support and exercising via constructs of self
      regulation, such as self-efficacy. This study aimed at examining an expanded
      enabling hypothesis by examining effects of different kinds of social support
      (i.e., emotional and instrumental) on exercising not only via self-efficacy but
      also via self-monitoring and action planning. DESIGN AND METHODS: An 8-week
      online study was conducted. Participants were randomly assigned to an
      intervention or a control group. The intervention comprised finding and then
      exercising regularly with a new exercise companion. Intervention and control
      group effects were compared by a manifest multigroup model. RESULTS: Received
      emotional social support predicted self-efficacy, self-monitoring, and action
      planning in the intervention group. Moreover, received emotional social support
      was indirectly connected with exercise via the examined mediators. The indirect
      effect from received emotional social support via self-efficacy mainly
      contributed to the total effect. No direct or indirect effect of received
      instrumental social support on exercise emerged. In the control group, neither
      emotional nor instrumental social support was associated with any of the self
      regulation constructs nor with exercise. CONCLUSION: Actively looking for a new
      exercise companion and exercising together seems to be beneficial for the
      promotion of received emotional and instrumental social support. Emotional
      support in turn promotes exercise by enabling better self-regulation, in
      particular self-efficacy. Statement of contribution What is already known on this
      subject? With the 'enabling hypothesis', Benight and Bandura (2004, Behav. Res.
      Ther., 42, 1129) claimed that social support indirectly affects behaviour via
      self-efficacy. Research in the domain of physical exercise has provided evidence
      for this enabling hypothesis on a correlational basis only preventing causal
      inferences. What does this study add? We found evidence for the enabling
      hypothesis of received social support via self-efficacy on physical exercise in
      an intervention study. Moreover, this study demonstrated the distinct
      contribution of received emotional and instrumental social support in the context
      of the enabling hypothesis.

PMID- 25854296
TI  - Increasing rates of brain tumours in the Swedish national inpatient register and
      the causes of death register.
AB  - Radiofrequency emissions in the frequency range 30 kHz-300 GHz were evaluated to
      be Group 2B, i.e., "possibly", carcinogenic to humans by the International Agency
      for Research on Cancer (IARC) at WHO in May 2011. The Swedish Cancer Register has
      not shown increasing incidence of brain tumours in recent years and has been used
      to dismiss epidemiological evidence on a risk. In this study we used the Swedish
      National Inpatient Register (IPR) and Causes of Death Register (CDR) to further
      study the incidence comparing with the Cancer Register data for the time period
      1998-2013 using joinpoint regression analysis. In the IPR we found a joinpoint in
      2007 with Annual Percentage Change (APC) +4.25%, 95% CI +1.98, +6.57% during 2007
      2013 for tumours of unknown type in the brain or CNS. In the CDR joinpoint
      regression found one joinpoint in 2008 with APC during 2008-2013 +22.60%, 95% CI
      +9.68, +37.03%. These tumour diagnoses would be based on clinical examination,
      mainly CT and/or MRI, but without histopathology or cytology. No statistically
      significant increasing incidence was found in the Swedish Cancer Register during
      these years. We postulate that a large part of brain tumours of unknown type are
      never reported to the Cancer Register. Furthermore, the frequency of diagnosis
      based on autopsy has declined substantially due to a general decline of autopsies
      in Sweden adding further to missing cases. We conclude that the Swedish Cancer
      Register is not reliable to be used to dismiss results in epidemiological studies
      on the use of wireless phones and brain tumour risk. 

PMID- 25854298
TI  - The influence of climacteric symptoms on women's lives and activities.
AB  - In the present study, we performed an analysis of the influence of climacteric
      symptoms on women's lives and activities, i.e. their quality of life (QoL). The
      study was performed between October 2011 and February 2012. It included 148 women
      aged 44-62. The study used a diagnostic survey with questionnaires. The research
      instrument was the Blatt-Kupperman index. The respondents were asked to complete
      a questionnaire on socio-demographic data, quality of life, and the influence of
      climacteric symptoms on life and its various aspects. The respondents
      experiencing moderate or severe climacteric symptoms also had stronger feelings
      of failure (p = 0.005), feeling that opportunities are still available (p =
      0.002), of losing their youth and beauty (p < 0.0001), compared to those who had
      slight or no symptoms. The intensity of climacteric symptoms significantly
      affects women's lives and activities, i.e., their QoL. The reported intensity of
      climacteric symptoms is influenced by the respondents' education, residence,
      marital status and professional activity. The more severe the climacteric
      symptoms, the lower the women's quality of life, as evidenced for example by the
      feeling of failure and of losing one's youth, beauty and opportunities. 

PMID- 25854297
TI  - Conceptual and operational considerations in identifying socioenvironmental
      factors associated with disability among community-dwelling adults.
AB  - Disability is conceived as a person-context interaction. Physical and social
      environments are identified as intervention targets for improving social
      participation and independence. In comparison to the body of research on place
      and health, relatively few reports have been published on residential
      environments and disability in the health sciences literature. We reviewed
      studies evaluating the socioenvironmental correlates of disability. Searches were
      conducted in Medline, Embase and CINAHL databases for peer-reviewed articles
      published between 1997 and 2014. We found many environmental factors to be
      associated with disability, particularly area-level socioeconomic status and
      rurality. However, diversity in conceptual and methodological approaches to such
      research yields a limited basis for comparing studies. Conceptual inconsistencies
      in operational measures of disability and conceptual disagreement between studies
      potentially affect understanding of socioenvironmental influences. Similarly,
      greater precision in socioenvironmental measures and in study designs are likely
      to improve inference. Consistent and generalisable support for socioenvironmental
      influences on disability in the general adult population is scarce. 

PMID- 25854299
TI  - Health impact assessment: improving its effectiveness in the enhancement of
      health and well-being.
AB  - Most countries in the world have Environmental Impact Assessment (EIA) processes
      and procedures to evaluate the potential impact of development projects on the
      environment. This process, which attempts to predict the potential adverse
      effects of the proposed development project on the environment, is normally
      legislated and is part of the approval process for the project. Although these
      processes have been effective in reducing the adverse impacts on the environment
      they have been limited in their ability to provide protection for the health and
      well-being of people affected by the development. [...]. 

PMID- 25854300
TI  - Primary cutaneous adenoid cystic carcinoma arising from folliculitis decalvans.

PMID- 25854301
TI  - Effects of unstable shoes on trunk muscle activity and lumbar spine kinematics.
AB  - BACKGROUND: In patients with neuromuscular disease and a forced vital capacity
      (FVC) of <30% of the predictive value, scoliosis correction operation was
      Background. An unstable shoe was developed as a walking device to strengthen the
      lower extremity muscles and reduce joint loading. A large number of studies have
      reported increased electromyographic (EMG) activity throughout the gait cycle in
      most of the lower limb muscles, and significant kinematic changes in the lower
      extremity. However, no studies have investigated the effects of wearing unstable
      shoes on spine kinematics and trunk muscle activity during gait. AIM: To compare
      trunk muscle activity and lumbar spine range of motion (ROM) during gait using an
      unstable shoe and a conventional stable control shoe. DESIGN: Cross-sectional
      study. SETTING: A Biomechanics laboratory. POPULATION: Forty-eight healthy
      voluntary participants (24.5+/-5.6 years and 22.7+/-6.8 kg/m2). METHODS: Subjects
      underwent gait analysis while simultaneously collecting surface EMG data of
      erector spinae (ES) and rectus abdominis (RA) and lumbar spine sagittal plane ROM
      while treadmill walking wearing regular shoes and unstable shoes. RESULTS: The
      results showed that the unstable shoes resulted in significantly higher ES and RA
      EMG muscle activity levels in all gait phases compared to control shoes
      (P<0.001). In addition, the unstable shoe condition showed a significantly higher
      mean (mean difference: 3.1o; 95% CI 2.2o to 4o) and maximum (mean difference:
      4.5o; 95% CI 2.6o to 6.5o) lumbar spine extension values (P<0.001). CONCLUSIONS:
      Unstable shoes increase trunk muscle activity (ES, RA) and lumbar lordosis during
      gait compared to control shoes. CLINICAL REHABILITATION IMPACT: Based on these
      findings, the use of unstable shoes may have potential implications in promoting
      spine tissue health, particularly in strengthening trunk muscles in healthy
      population or in low back pain treatment.

PMID- 25854302
TI  - Motivation-cognition interaction: how feedback processing changes in healthy
      ageing and in Parkinson's disease.
AB  - BACKGROUND: Several studies have investigated the interaction between motivation
      and cognition in both young and older adults, but with inconsistent results. A
      recent hypothesis suggests exploring the role of dopamine to study this
      interaction. AIMS: To explore how different motivational states can modulate
      cognitive control, as well as investigate the hypothesis of a dopaminergic role
      in this phenomenon. METHODS: 27 young subjects, 15 healthy old subjects, and 15
      Parkinson's disease (PD) patients took part in this study. The motivational Simon
      task-a new paradigm in which rewards and punishments are delivered to promote
      fast and accurate responses-was employed. The participants' performance was
      evaluated by analysing their reaction times and accuracy, while employing a
      diffusion model analysis. RESULTS: The employment of positive and negative
      feedback significantly modulated performance in a conflict task. In both, the
      young and older participants, the speed-accuracy trade-off significantly changed
      in response to different motivational incentives (p < .005), although in opposite
      ways. On the contrary, PD patients showed an absence of performance modulation in
      response to positive and negative feedback. DISCUSSION AND CONCLUSIONS: In normal
      conditions, motivation interacts with cognitive control to modulate decisional
      aspects of a response in a conflict task. The elderly modulate their performance
      in response to positive and negative feedback differently from young adults,
      showing a classical positivity effect. The impairment manifested by PD patients,
      which is compatible with the literature about feedback processing deficits in
      this clinical condition, can support the hypothesis that the interaction between
      motivation and cognitive control is mediated by dopaminergic functionality.

PMID- 25854303
TI  - Short-term administration of GW501516 improves inflammatory state in white
      adipose tissue and liver damage in high-fructose-fed mice through modulation of
      the renin-angiotensin system.
AB  - High activation of the angiotensin-converting enzyme (ACE)/(angiotensin-II type 1
      receptor) AT1r axis is closely linked to pro-inflammatory effects and liver
      damage. The aim of this study was to evaluate the effects of the short-term
      administration of GW501516 on pro-inflammatory markers in white adipose tissue
      (WAT) and hepatic stellate cells (HSCs), lipogenesis and insulin resistance in
      the liver upon high-fructose diet (HFru)-induced ACE/AT1r axis activation. Three
      month-old male C57Bl/6 mice were fed a standard chow diet or a HFru for 8 weeks.
      Then, the animals were separated randomly into four groups and treated with
      GW501516 for 3 weeks. Morphological variables, systolic blood pressure, and
      plasma determinations were analyzed. In the WAT, the ACE/AT1r axis and pro
      inflammatory cytokines were assessed, and in the liver, the ACE/AT1r axis, HSCs,
      fatty acid oxidation, insulin resistance, and AMPK activation were evaluated. The
      HFru group displayed a high activation of the ACE/AT1r axis in both the WAT and
      liver; consequently, we detected inflammation and liver damage. Although GW501516
      abolished the increased activation of the ACE/AT1r axis in the WAT, no
      differences were found in the liver. GW501516 blunted the inflammatory state in
      the WAT and reduced HSC activation in the liver. In addition, GW501516 alleviates
      damage in the liver by increasing the expression of the genes that regulate beta
      oxidation and decreasing the expression of the genes and proteins that are
      involved in lipogenesis and gluconeogenesis. We conclude that GW501516 may serve
      as a therapeutic option for the treatment of a highly activated ACE/AT1r axis in
      WAT and liver. 

PMID- 25854305
TI  - The "fishnet" appearance.

PMID- 25854304
TI  - The expression of the truncated isoform of somatostatin receptor subtype 5
      associates with aggressiveness in medullary thyroid carcinoma cells.
AB  - The truncated somatostatin receptor variant sst5TMD4 associates with increased
      invasiveness and aggressiveness in breast cancer. We previously found that sst5
      activation may counteract sst2 selective agonist effects in a medullary thyroid
      carcinoma (MTC) cell line, the TT cells, and that sst5TMD4 is overexpressed in
      poorly differentiated thyroid cancers. The purpose of this study is to evaluate
      sst5TMD4 expression in a series of human MTC and to explore the functional role
      of sst5TMD4 in TT cells. We evaluated sst5TMD4 and sst5 expression in 36 MTC
      samples. Moreover, we investigated the role of sst5TMD4 in TT cells evaluating
      cell number, DNA synthesis, free cytosolic calcium concentration ([Ca(2+)]i),
      calcitonin and vascular endothelial growth factor levels, cell morphology,
      protein expression, and invasion. We found that in MTC the balance between
      sst5TMD4 and sst5 expression influences disease stage. sst5TMD4 overexpression in
      TT cells confers a greater growth capacity, blocks sst2 agonist-induced
      antiproliferative effects, modifies the cell phenotype, decreases E-cadherin and
      phosphorylated beta-catenin levels, increases vimentin, total beta-catenin and
      phosphorylated GSK3B levels (in keeping with the development of epithelial to
      mesenchymal transition), and confers a greater invasion capacity. This is the
      first evidence indicating that sst5TMD4 is expressed in human MTC cells, where it
      associates with more aggressive behavior, suggesting that sst5TMD4 might play a
      functionally relevant role. 

PMID- 25854306
TI  - Clinical significance of Candida colonization of central vascular catheters in
      patients with major burns requiring intensive care.

PMID- 25854307
TI  - An accurate method of determining a single-plane osteotomy to correct a combined
      rotational and angular deformity.
AB  - Conventional osteotomy used for the correction of deformity is performed out of
      the plane of deformity creating a wedge either opening or closing when the
      deformity is corrected. Deformity that is a combination of rotation and
      angulation exists in a single plane that is oblique to the coronal, sagittal and
      axial planes depending on the magnitude of deformity measured in each plane.
      Accurate planning and a simple method of finding this oblique plane operatively
      is presented. This method starts by finding the bisector of angulation. This is
      marked by a wire that lies in the plane of angulation and along the bisector of
      angulation. The saw blade is rotated about this bisector axis according to the
      proportion of angulation and rotation. There is no second reorientation of the
      saw blade required making the final plane much easier to define. This single
      plane oblique osteotomy allows accurate realignment of the limb. 

PMID- 25854308
TI  - Sulfasalazine-induced DRESS and severe agranulocytosis successfully treated by
      granulocyte colony-stimulating factor.
AB  - INTRODUCTION: A drug reaction with eosinophilia and systemic symptom (DRESS) is a
      severe and rare adverse-drug hypersensitivity syndrome. The evolution of DRESS is
      unpredictable and haematological abnormalities may occur in 50 % of cases.
      Sulfasalazine (SSZ) is rarely associated with DRESS. Agranulocytosis is a rare
      but recognized side-effect to SSZ. Both DRESS and agranulocytosis were not
      reported previously with SSZ. We report a case of SSZ-induced DRESS followed by
      severe agranulocytosis occurring in a 25-year-old man. The patient's general
      condition and laboratory tests gradually improved after the administration of
      granulocyte colony-stimulating factor (GCSF). DISCUSSION: In our patient, the co
      occurrence of DRESS and agranulocytosis is unlikely to be coincidental.
      Immunological mechanisms may play an important role in drug associated
      agranulocytosis in patients presenting DRESS. According to the Naranjo's
      algorithm the likelihood that our patient's DRESS and agranulocytosis occurred as
      a result of therapy with SSZ is probable. G-CSF was found to be useful in
      shortening the duration of granulocyte recovery in drug-induced agranulocytosis.
      CONCLUSION: Careful monitoring of neutrophil counts is required on SSZ therapy as
      well as in the course of DRESS.

PMID- 25854309
TI  - Implementing clinical pharmacy within undergraduate teaching in Namibia.
AB  - Clinical pharmacy is currently not practised in Namibia. To introduce the concept
      and skills pertinent to this area of practice, pharmacy undergraduates at
      Namibia's new School of Pharmacy are introduced to clinical pharmacy from their
      second year, and progress from theory to practical application on the wards. This
      approach has led to students having a greater understanding of clinical pharmacy
      and how it can be applied in practice. Introducing clinical pharmacy
      progressively at an undergraduate level may help to stimulate interest in the
      speciality for future career progression. 

PMID- 25854311
TI  - The rationale for use of progesterone in the prevention of preterm birth?

PMID- 25854310
TI  - Medication use during end-of-life care in a palliative care centre.
AB  - BACKGROUND: In end-of-life care, symptoms of discomfort are mainly managed by
      drug therapy, the guidelines for which are mainly based on expert opinions. A few
      papers have inventoried drug prescriptions in palliative care settings, but none
      has reported the frequency of use in combination with doses and route of
      administration. OBJECTIVE: To describe doses and routes of administration of the
      most frequently used drugs at admission and at day of death. Setting Palliative
      care centre in the Netherlands. METHOD: In this retrospective cohort study,
      prescription data of deceased patients were extracted from the electronic medical
      records. MAIN OUTCOME MEASURE: Doses, frequency and route of administration of
      prescribed drugs RESULTS: All regular medication prescriptions of 208 patients,
      89% of whom had advanced cancer, were reviewed. The three most prescribed drugs
      were morphine, midazolam and haloperidol, to 21, 11 and 23% of patients at
      admission, respectively. At the day of death these percentages had increased to
      87, 58 and 50%, respectively. Doses of these three drugs at the day of death were
      statistically significantly higher than at admission. The oral route of
      administration was used in 89% of patients at admission versus subcutaneous in
      94% at the day of death. CONCLUSIONS: Nearing the end of life, patients in this
      palliative care centre receive discomfort-relieving drugs mainly via the
      subcutaneous route. However, most of these drugs are unlicensed for this specific
      application and guidelines are based on low level of evidence. Thus, there is
      every reason for more clinical research on drug use in palliative care.

PMID- 25854312
TI  - Pd-catalyzed carbonylative access to aroyl phosphonates from (hetero)aryl
      bromides.
AB  - The first transition-metal catalysed carbonylation with a phosphorus nucleophile
      is presented. This transformation provides efficient and mild access to
      aroylphosphonates under mild conditions, thus ensuring a broad substrate scope.
      The utility of aroylphosphonates as useful reagents, capable of participating in
      a number of transformations, is subsequently demonstrated. Furthermore, access to
      [(13)C]-carbonyl labelled aroylphosphonates is easily realised for the first
      time, as only a near stoichiometric amount of CO is required applying this
      carbonylation. 

PMID- 25854313
TI  - Aptamer-based colorimetric biosensing of abrin using catalytic gold
      nanoparticles.
AB  - In this study we propose a simple and sensitive colorimetric aptasensor for the
      quantitative analysis of abrin by using catalytic AuNPs for the first time. AuNPs
      possess the peroxidase-like activity that can catalyse 3,3,5,5
      tetramethylbenzidine (TMB) in the presence of H2O2, leading to color change of
      the solution. It is interesting to find that the peroxidase-like activity of
      AuNPs can be improved by surface activation with a target-specific aptamer.
      However, with a target molecule, the aptamer is desorbed from the AuNPs surface,
      resulting in a decrease of the catalytic abilities of AuNPs. The color change of
      the solution is relevant to the target concentration, and this can be judged by
      the naked eye and monitored by using a UV-vis spectrometer. The linear range for
      the current analytical system was from 0.2 nM to 17.5 nM. The corresponding limit
      of detection (LOD) was 0.05 nM. Some other proteins such as thrombin (Th),
      glucose oxidase (GOx), and bovine serum albumin (BSA) all had a negligible effect
      on the determination of abrin. Furthermore, several practical samples spiked with
      abrin were analyzed using the proposed method with excellent recoveries. This
      aptamer-based colorimetric biosensor is superior to other conventional methods
      owing to its simplicity, low cost, and high sensitivity. 

PMID- 25854314
TI  - pH-Sensitive gold nanoclusters: preparation and analytical applications for urea,
      urease, and urease inhibitor detection.
AB  - Herein, we reported for the first time a facile synthetic process of gold
      nanoclusters (AuNCs) by using N-acetyl-L-cysteine both as a reducing agent and as
      a protection ligand. Based on the pH stimuli-responsive properties of the as
      prepared AuNCs, we constructed a pH-sensing platform for the detection of urea,
      urease, and urease inhibitors.

PMID- 25854315
TI  - [The National Elderly Care program 'on steam'; joining, spreading and entering
      the profits].

PMID- 25854316
TI  - Dose-dependent effect of 2-deoxy-D-glucose on glycoprotein mannosylation in
      cancer cells.
AB  - High glucose consumption due to Warburg effect is one of the metabolic hallmarks
      of cancer. Consequently, glucose antimetabolites, such as 2-deoxy-glucose (2DG),
      can induce substantial growth inhibition of cancer cells. However, the inhibition
      of metabolic pathways is not the sole effect of 2DG on cancer cells. As mannose
      mimetic molecule, 2DG is believed to interfere with normal glycosylation of
      proteins in cells. Here, we address how 2DG influences protein glycosylation in
      cancer cells and discuss possible implications of the consequences of this
      influence. In detail, six colorectal cancer cell lines were examined for
      alterations of protein glycosylation by measuring monosaccharide incorporation
      into cellular glycoproteins and cell surface glycosylation by lectin FACS. A
      significant increase in mannose incorporation was observed on treatment with 2DG
      (1 mM for 48 h), which was also reflected by an increased binding of the mannose
      binding lectin Concanavalin A in FACS analysis. This phenomenon, which could be
      reversed by external addition of mannose, was not caused by 2DG-mediated
      mannosidase inhibition, as shown by pulse-chase experiments, arguing in favor of
      the hypothesis that 2DG directly influenced the incorporation of mannose.
      Increased mannose content was generally observed in cellular glycoproteins,
      including glycoproteins isolated from the plasma membrane fraction. Our results
      indicate that 2DG at low doses, which have only a limited metabolism-related
      effect on glycosylation, induces a strong increase in mannose incorporation into
      cellular glycoproteins. On the other hand, higher 2DG concentrations (10 and 20
      mM) led to a significant decrease of absolute mannose incorporation accompanied
      by a dramatically reduced protein synthesis rate. 2DG-induced alterations of
      glycosylation may represent a novel mechanism potentially explaining the varied
      effects of 2DG on cancer cells. Moreover, 2DG treatment may open a path toward
      novel diagnostic and cancer therapeutic approaches, which specifically target
      altered glycoantigen structures induced by 2DG.

PMID- 25854317
TI  - A new mutation in the KINDLIN-3 gene ablates integrin-dependent leukocyte,
      platelet, and osteoclast function in a patient with leukocyte adhesion deficiency
      III.
AB  - Disabling mutations in integrin-mediated cell signaling have been a major focus
      of interest over the last decade for patients affected with leukocyte adhesion
      deficiency-III (LAD-III). In this study, we identified a new C>T point mutation
      in exon 13 in the FERMT3 gene in an infant diagnosed with LAD-III and showed that
      KINDLIN-3 expression is required for platelet aggregation and leukocyte function,
      but also osteoclast-mediated bone resorption. After allogeneic bone marrow
      transplant, all overt symptoms disappeared. This newly identified mutation along
      with its novel role in dysregulation of bone homeostasis extends our
      understanding of KINDLIN-3 in humans.

PMID- 25854319
TI  - Intrinsic religiousness and spirituality as predictors of mental health and
      positive psychological functioning in Latter-Day Saint adolescents and young
      adults.
AB  - We investigated the relationships between religiousness and spirituality and
      various indicators of mental health and positive psychosocial functioning in
      three separate samples of college students. A total of 898 students at Brigham
      Young University participated in the three studies. The students ranged in age
      from 17 to 26 years old, with the average age of 20.9 across all three samples.
      Our results indicate that intrinsic religiousness, spiritual maturity, and self
      transcendence were significantly predictive of better mental health and positive
      functioning, including lower levels of depression, anxiety, and obsessive
      compulsiveness, and higher levels of global self-esteem, identity integration,
      moral self-approval, and meaning in life. Intrinsic religiousness was not
      predictive of shame, perfectionism, and eating disorder symptoms. These findings
      are consistent with many prior studies that have found religiousness and
      spirituality to be positively associated with better mental health and positive
      psychosocial functioning in adolescents and young adults. 

PMID- 25854318
TI  - Computer-assisted staging of chronic rhinosinusitis correlates with symptoms.
AB  - BACKGROUND: The Lund-Mackay (LM) staging system for chronic rhinosinusitis (CRS)
      does not correlate with clinical parameters, likely due to its coarse scale. We
      developed a "Modified Lund Mackay" (MLM) system, which uses a three-dimensional
      (3D), computerized method to quantify the volume of mucosal inflammation in the
      sinuses, and sought to determine whether the MLM would correlate with symptoms
      and disease-specific quality of life. METHODS: We obtained Total Nasal Symptom
      Score (TNSS) and 22-item Sino-Nasal Outcome Test (SNOT-22) data from 55 adult
      subjects immediately prior to sinus imaging. The volume of each sinus occupied by
      mucosal inflammation was measured using MATLAB algorithms created using
      customized, image analysis software after manual outlining of each sinus. Linear
      regression was used to model the relationship between the MLM and the SNOT-22 and
      TNSS. Correlation between the LM and MLM was tested using Spearman's rank
      correlation coefficient. RESULTS: Adjusting for age, gender, and smoking, a
      higher symptom burden was associated with increased sinonasal inflammation as
      captured by the MLM (beta = 0.453, p < 0.013). As expected due to the differences
      in scales, the LM and MLM scores were significantly different (p < 0.011). No
      association between MLM and SNOT-22 scores was found. CONCLUSION: The MLM is one
      of the first imaging-based scoring systems that correlates with sinonasal
      symptoms. Further development of this custom software, including full automation
      and validation in larger samples, may yield a biomarker with great utility for
      both treatment of patients and outcomes assessment in clinical trials.

PMID- 25854320
TI  - Guest editor note.

PMID- 25854321
TI  - HSP70 expression in dentigerous cyst, odontogenic keratocyst, and ameloblastoma.
AB  - Heat shock proteins (HSPs) work as molecular chaperones that can assist cells to
      deal with stressful situations. Members of the HSP70 family can regulate cell
      growth and transformation and are involved in the maintenance of cellular
      homeostasis. In view of the distinct clinical behavior of odontogenic lesions,
      the objective of the present study was to investigate the immunohistochemical
      expression of HSP70 in these lesions. In this study, 70 formalin-fixed paraffin
      embedded tissue blocks of odontogenic lesion-16 unicystic ameloblastomas (UAs),
      17 solid ameloblastomas (SAs), 18 odontogenic keratocysts (OKCs), and 19
      dentigerous cysts (DCs)-were reviewed by immunohistochemistry for HSP70 staining.
      In this study, HSP70 immunostaining was evident in all groups of the specimen.
      Mean percentage of HSP70 staining in SAs (84.2 +/- 11.3) and OKCs (83.4 +/- 6.8)
      were significantly higher than UAs (64.4 +/- 9.8) and DCs (12.6 +/- 10.2) (p =
      0.00). But, there was no statistically significant difference between HSP70
      expression in SAs and OKCs. The result of this study proposes that high
      expression rate of HSP70 has a role in the pathogenesis of ameloblastoma and OKC
      and is one of the reasons for the aggressive behavior of ameloblastoma and high
      recurrence role of OKC, reinforcing the classification of OKC as an odontogenic
      tumor.

PMID- 25854322
TI  - Placental perfusion in uterine ischemia model as evaluated by dynamic contrast
      enhanced MRI.
AB  - BACKGROUND: To validate DCE MRI method of placental perfusion estimation and to
      demonstrate application of the method in a rabbit model of fetal antenatal
      hypoxia-ischemia. METHODS: Placental perfusion was estimated by dynamic contrast
      imaging with bolus injection of Gd-DTPA in 3 Tesla GE magnet in a rabbit model of
      placental ischemia-reperfusion in rabbit dams at embryonic day 25 gestation age.
      Placental perfusion was measured using steepest slope method on DCE MRI before
      and after intermittent 40 min uterine ischemia. Antioxidants (n = 2 dams, 9
      placentas imaged) or vehicle (n = 5 dams, 23 placenta imaged) were given
      systemically in a separate group of dams during reperfusion-reoxygenation.
      Placental perfusion was also measured in two dams from the antioxidant group (10
      placentas) and two dams from the control group (12 placentas) by fluorescent
      microspheres method. RESULTS: While placental perfusion estimates between
      fluorescent microspheres and DCE MRI were significantly correlated (R(2)  = 0.85;
      P < 0.01), there was approximately 33% systematic underestimation by the latter
      technique. DCE MRI showed a significant decrease in maternal placental perfusion
      in reperfusion-reoxygenation phase in the saline, 0.44 +/- 0.06 mL/min/g (P =
      0.012, t-test), but not in the antioxidant group, 0.62 +/- 0.06 mL/min/g,
      relative to pre-occlusion values (0.77 +/- 0.07 and 0.84 +/- 0.12 mL/min/g,
      correspondingly). CONCLUSION: Underestimation of true perfusion in placenta by
      steepest slope DCE MRI is significant and the error appears to be systematic.

PMID- 25854323
TI  - Impaired aquaporins expression in the gastrointestinal tract of rat after mercury
      exposure.
AB  - The main route of exposure to mercury in humans is through the diet.
      Consequently, the gastrointestinal mucosa is exposed to the mercurial forms,
      where they cause intestinal fluid accumulation, mucosal injuries and diarrhea.
      The relationship between inorganic mercury (HgCl2 ) and methylmercury (CH3 HgCl)
      exposure and water movement in the gastrointestinal tract is still unexplored.
      The leading role of aquaporins (AQPs) in the rapid bidirectional movement of
      fluid in the gastrointestinal tract of mammals is well established. The present
      study evaluates the effect of HgCl2 and CH3 HgCl exposure on AQP expression in
      different portions of the gastrointestinal tract of rats treated by gavage (5 mg
      kg(-1) of mercury species, single dose, 4 days). The results show that mercury
      species reduce mRNA and protein levels of AQPs in different parts of the
      gastrointestinal tract. In the stomach, treated rats show a significant reduction
      of expression of AQP3 (80-90% for mRNA and 50% for protein) and AQP4 (95-99% for
      mRNA and 20-40% for protein). In the small and large intestine, treated rats
      experience a significant reduction of AQP3 and AQP7 expression. Protein contents
      of both AQPs are reduced in similar proportions in jejunum (AQP3: 40-50%; AQP7:
      45-50%) and colon (AQP3: 35-40%; AQP7: 45-60%), regardless of the treatment. Our
      results indicate that some AQPs are downregulated in the rat gastrointestinal
      tract by mercury exposure, suggesting a possible role of AQPs in the development
      of mercury gastrointestinal symptoms.

PMID- 25854324
TI  - "Anion clamp" allows flexible protein to impose coordination geometry on metal
      ions.
AB  - X-ray crystal structures of human serum transferrin (77 kDa) with Yb(III) or
      Fe(III) bound to the C-lobe and malonate as the synergistic anion show that the
      large Yb(III) ion causes the expansion of the metal binding pocket while
      octahedral metal coordination geometry is preserved, an unusual geometry for a
      lanthanide ion. 

PMID- 25854325
TI  - Holey tungsten oxynitride nanowires: novel anodes efficiently integrate microbial
      chemical energy conversion and electrochemical energy storage.
AB  - Holey tungsten oxynitride nanowires with superior conductivity, good
      biocompatibility, and good stability achieve excellent performance as anodes for
      both asymmetric supercapacitors and microbial fuel cells. Moreover, an innovative
      system is devised based on these as-prepared tungsten oxynitride anodes, which
      can simultaneously realize both energy conversion from chemical to electric
      energy and its storage. 

PMID- 25854326
TI  - The Other Side of the RAAS: Aldosterone Improves Migration of Cardiac Progenitor
      Cells.
AB  - Stem cell therapy is a promising new option for patients suffering from heart
      failure. Though many clinical studies show encouraging results, little is known
      about the signals which cause stem cells to home to diseased but not to healthy
      hearts. We hypothesized that aldosterone as one of the main players of heart
      failure functions as an attractant for progenitor cells and stimulates their
      migration. Stem cell antigen-1 (Sca-1) positive cells were isolated from the
      hearts of wild type FVB mice via magnetic cell sorting. The migration rate of the
      cells was determined using aldosterone as an attractant in a modified Boyden
      chamber (n = 5). Aldosterone led to a dose dependent increase in migration rate
      and this effect could be prevented by adding its blocker eplerenone. The
      mineralocorticoid receptor could be detected on Sca-1+ cells via western blot and
      immunofluorescence. Therefore, aldosterone seems to play a role in stem cell
      migration and there the effect is most likely mediated by the mineralocorticoid
      receptor.

PMID- 25854327
TI  - Conservative treatment for incontinence in women in rest home care in
      Christchurch: Outcomes and cost.
AB  - AIMS: To assess if conservative therapy can reduce urinary leakage and pad usage
      and improve quality of life in elderly incontinent women living in a rest home
      setting; and if so at what additional cost. METHODS: Sixty-eight elderly women
      with urinary incontinence, and preserved cognitive ability, living in 26 rest
      homes were identified. Clinical evaluation, included bladder diary, pad weigh
      tests, pad usage, and quality of life and activities questionnaires (FIM:
      Functional Impairment Measure; EQ-5D: Euroquol 5 dimension score; ICIQ-SF:
      International Consultation on Incontinence-Short Form). A specialist Continence
      Advisor Nurse provided conservative treatment according to the needs of each
      participant. Outcomes were recorded after 12 weeks of treatment by repeating
      above evaluations, and the costs involved were measured. RESULTS: Leakage was
      reduced by a mean of 60 ml per 24 hr, and four fewer pads were required per week.
      The ICIQ-SF improved significantly. The EQ-5D did not demonstrate significant
      improvement, so a cost-utility analysis was not possible. The mean cost of the
      Advisor's time and mileage in providing the 12 week course was $247.75 per
      participant. CONCLUSION: Conservative therapies tailored to each individual, can
      improve the severity of leakage in the short term, even in this elderly group of
      women with preserved cognitive function, at modest additional cost. Measuring
      quality of life and the impact of incontinence, has challenges in this age group.
      Neurourol. Urodynam. 35:636-641, 2016. (c) 2015 Wiley Periodicals, Inc.

PMID- 25854328
TI  - Towards understanding abscisic acid-mediated leaf senescence.

PMID- 25854329
TI  - Diffusion of molecules in the bulk of a low density amorphous ice from molecular
      dynamics simulations.
AB  - The diffusion of molecules in interstellar ice is a fundamental phenomenon to
      take into account while studying the formation of complex molecules in this ice.
      This work presents a theoretical study on the diffusion of H2O, NH3, CO2, CO, and
      H2CO in the bulk of a low density amorphous (LDA) ice, while taking into account
      the physical conditions prevailing in space, i.e. temperatures below 150 K and
      extremely low pressure. This study was undertaken by means of molecular dynamics
      simulations. For CO2 for which no experimental data were available we conducted
      our own experiments. From our calculations we show that, at low temperatures, the
      diffusion of molecules in the bulk of a LDA ice is driven by the self-diffusion
      of water molecules in the ice. With this study we demonstrate that molecular
      dynamics allows the calculation of diffusion coefficients for small molecules in
      LDA ice that are convincingly comparable to experimentally measured diffusion
      coefficients. We also provide diffusion coefficients for a series of molecules of
      astrochemical interest. 

PMID- 25854330
TI  - Engineering of an all-heteronuclear 5-qubit NMR quantum computer.
AB  - The realization of an all-heteronuclear 5-qubit nuclear magnetic resonance
      quantum computer is reported, from the design and synthesis of a suitable
      molecule through the engineering of a prototype 6-channel probe head. Full
      control over the quantum computer is shown by a benchmark experiment.

PMID- 25854331
TI  - Telerehabilitation for persons with multiple sclerosis.
AB  - BACKGROUND: Telerehabilitation, an emerging method, extends rehabilitative care
      beyond the hospital, and facilitates multifaceted, often psychotherapeutic
      approaches to modern management of patients using telecommunication technology at
      home or in the community. Although a wide range of telerehabilitation
      interventions are trialed in persons with multiple sclerosis (pwMS), evidence for
      their effectiveness is unclear. OBJECTIVES: To investigate the effectiveness and
      safety of telerehabilitation intervention in pwMS for improved patient outcomes.
      Specifically, this review addresses the following questions: does
      telerehabilitation achieve better outcomes compared with traditional face-to-face
      intervention; and what types of telerehabilitation interventions are effective,
      in which setting and influence which specific outcomes (impairment, activity
      limitation and participation)? SEARCH METHODS: We performed a literature search
      using the Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous
      System Review Group Specialised Register( 9 July, 2014.) We handsearched the
      relevant journals and screened the reference lists of identified studies, and
      contacted authors for additional data. SELECTION CRITERIA: Randomised controlled
      trials (RCTs) and controlled clinical trials (CCTs) that reported
      telerehabilitation intervention/s in pwMS and compared them with some form of
      control intervention (such as lower level or different types of intervention,
      minimal intervention, waiting-list controls or no treatment (or usual care);
      interventions given in different settings) in adults with MS. DATA COLLECTION AND
      ANALYSIS: Two review authors independently selected studies and extracted data.
      Three review authors assessed the methodological quality of studies using the
      GRADEpro software (GRADEpro 2008) for best-evidence synthesis. A meta-analysis
      was not possible due to marked methodological, clinical and statistical
      heterogeneity between included trials and between measurement tools used. Hence,
      we performed a best-evidence synthesis using a qualitative analysis. MAIN
      RESULTS: Nine RCTs, one with two reports, (N = 531 participants, 469 included in
      analyses) investigated a variety of telerehabilitation interventions in adults
      with MS. The mean age of participants varied from 41 to 52 years (mean 46.5
      years) and mean years since diagnosis from 7.7 to 19.0 years (mean 12.3 years).
      The majority of the participants were women (proportion ranging from 56% to 87%,
      mean 74%) and with a relapsing-remitting course of MS. These interventions were
      complex, with more than one rehabilitation component and included physical
      activity, educational, behavioural and symptom management programmes.All studies
      scored 'low' on the methodological quality assessment. Overall, the review found
      'low-level' evidence for telerehabilitation interventions in reducing short-term
      disability and symptoms such as fatigue. There was also 'low-level' evidence
      supporting telerehabilitation in the longer term for improved functional
      activities, impairments (such as fatigue, pain, insomnia); and participation
      measured by quality of life and psychological outcomes. There were limited data
      on process evaluation (participants'/therapists' satisfaction) and no data
      available for cost effectiveness. There were no adverse events reported as a
      result of telerehabilitation interventions. AUTHORS' CONCLUSIONS: There is
      currently limited evidence on the efficacy of telerehabilitation in improving
      functional activities, fatigue and quality of life in adults with MS. A range of
      telerehabilitation interventions might be an alternative method of delivering
      services in MS populations. There is insufficient evidence to support on what
      types of telerehabilitation interventions are effective, and in which setting.
      More robust trials are needed to build evidence for the clinical and cost
      effectiveness of these interventions.

PMID- 25854332
TI  - Synthesis and characterization of heterofluorenes containing four-coordinated
      group 13 elements: theoretical and experimental analyses and comparison of
      structures, optical properties and electronic states.
AB  - Herein, we report the syntheses of dibenzoheteroles, namely, heterofluorenes,
      containing four-coordinated group 13 elements (boron Bf; aluminum Alf; gallium
      Gaf; indium Inf) and the relationship between their structures and optical
      properties. The electronic states of the compounds were considered theoretically
      by the density functional theory (DFT) calculation. In particular, we focused on
      their emission behaviors and electronic structures in the excited states.
      Initially, we confirmed that Bf and Gaf showed high stability in water and air,
      while Alf and Inf were sensitive. The structures of heterofluorenes, involving
      the heavier elements in the 13(th) group, tend to form trigonal planar structures
      even in the presence of coordination by nitrogen. Next, in their emissions,
      larger contribution from the triplet excited states was observed in the
      heterofluorenes with heavier elements. The major emission of Inf at 77 K was
      attributed to phosphorescence. These phosphorescence properties can be explained
      by the heavy atom effect. In Gaf and Inf, their excited states were deactivated
      by vibrational relaxation in their triplet excited states at room temperature. In
      Bf, Alf and Gaf when adding B(C6F5)3, the emissions oriented from the triplet
      exciplex were observed. Time-dependent DFT (TD-DFT) calculations revealed that
      the optimized structure of Bf in the excited S1 state has a considerably
      different geometry from those of Alf and Gaf. Finally, we obtained the data that
      the B-N bond could be cleaved in the excited S1 of Bf according to the B-N bond
      length and bond order. As a result, the lower intensity of the emission of Bf was
      comparable to that of Alf. This bond cleavage could be caused by an increase of
      the anti-bonding property in the B-N bond in the Franck-Condon (FC) S1 state and
      by weak electrostatic interaction between boron and nitrogen atoms. In Alf and
      Gaf, although the anti-bonding character of the M-N bonds (M = Al or Ga) in the
      FC S1 states also increases, the M-N bonds survive because of their stronger
      electrostatic interaction. The subsequent stronger emission in Alf and Gaf could
      be observed by suppressing the molecular motion in the excited states. 

PMID- 25854333
TI  - Clarification of the APJCP editorial policy.

PMID- 25854334
TI  - Recent progress in HER2 associated breast cancer.
AB  - Breast cancer is the most common cancer worldwide among women and the second most
      common cancer. Approximately 15-23% of breast cancers over-express human
      epidermal growth factor receptor2 (HER2), a 185-kDa transmembrane tyrosine
      kinase, which is mainly found at the cell surface of tumor cells. HER2-positive
      breast cancer, featuring amplification of HER2/neu and negative expression of ER
      and PR, has the three following characteristics: rapid tumor growth, lower
      survival rate, and better response to adjuvant therapies. Clinically, it is
      notable for its role in a pathogenesis that is associated with increased disease
      recurrence and acts as a worse prognosis. At the same time, it represents a good
      target for anti-cancer immunotherapy despite the prevalence of drug resistance.
      New treatments are a major topic of research, and a brighter future can be
      expected. This review discusses the role of HER2 in breast cancer, therapeutic
      modalities available and prognostic factors. 

PMID- 25854335
TI  - Biomarkers for evaluation of prostate cancer prognosis.
AB  - Prostate cancer, with a lifetime prevalence of one in six men, is the second
      cause of malignancy-related death and the most prevalent cancer in men in many
      countries. Nowadays, prostate cancer diagnosis is often based on the use of
      biomarkers, especially prostate-specific antigen (PSA) which can result in
      enhanced detection at earlier stage and decreasing in the number of metastatic
      patients. However, because of the low specificity of PSA, unnecessary biopsies
      and mistaken diagnoses frequently occur. Prostate cancer has various features so
      prognosis following diagnosis is greatly variable. There is a requirement for new
      prognostic biomarkers, particularly to differentiate between inactive and
      aggressive forms of disease, to improve clinical management of prostate cancer.
      Research continues into finding additional markers that may allow this goal to be
      attained. We here selected a group of candidate biomarkers including PSA, PSA
      velocity, percentage free PSA, TGFbeta1, AMACR, chromogranin A, IL-6, IGFBPs,
      PSCA, biomarkers related to cell cycle regulation, apoptosis, PTEN, androgen
      receptor, cellular adhesion and angiogenesis, and also prognostic biomarkers with
      Genomic tests for discussion. This provides an outline of biomarkers that are
      presently of prognostic interest in prostate cancer investigation. 

PMID- 25854336
TI  - Radiation induced lung injury: prediction, assessment and management.
AB  - Radiation induced lung injury has long been considered a treatment limiting
      factor for patients requiring thoracic radiation. This radiation induced lung
      injury happens early as well as late. Radiation induced lung injury can occur in
      two phases viz. early (<6 months) when it is called radiation pneumonitis and
      late (>6 months) when it is called radiation induced lung fibrosis. There are
      multiple factors that can be patient, disease or treatment related that predict
      the incidence and severity of radiation pneumonitis. Radiation induced damage to
      the type I pneumocytes is the triggering factor to initiate such reactions. Over
      the years, radiation therapy has witnessed a paradigm shift in radiation planning
      and delivery and successfully reduced the incidence of lung injury. Radiation
      pneumonitis is usually a diagnosis of exclusion. Steroids, ACE inhibitors and
      pentoxyphylline constitute the cornerstone of therapy. Radiation induced lung
      fibrosis is another challenging aspect. The pathophysiology of radiation fibrosis
      includes continuing inflammation and microvascular changes due to pro-angiogenic
      and pro- fibrogenic stimuli resembling those in adult bronchiectasis. General
      supportive management, mobilization of airway secretions, anti-inflammatory
      therapy and management of acute exacerbations remains the treatment option.
      Radiation induced lung injury is an inevitable accompaniment of thoracic
      radiation.

PMID- 25854337
TI  - Selenium and vitamin E for prostate cancer--justifications for the SELECT study.
AB  - There are several studies that relate oxidative damage as possible mechanism for
      many cancers. Many studies have also shown that anti-oxidants like selenium and
      vitamin E decrease the risk for prostate cancer. The main objective of the
      Selenium and Vitamin E Cancer Prevention Trial (SELECT) study was to look for the
      benefits of selenium and vitamin E supplementation on prostate cancer. The study
      had a large sample size, stringent experimental conditions, very long duration,
      standardized laboratories for biochemical analyses and other factors that
      contribute to high external validity. The SELECT study failed to show any
      significant risk reduction for prostate cancers ascribable to selenium and
      vitamin E supplementations. Because of these conflicting results, many
      researchers argue about the methods used, supplementations administered (selenium
      and vitamin E) and indicators used for assessing levels of supplementations. We
      reviewed many epidemiological studies, clinical trials, and pre-clinical studies.
      With corroborative evidences we justify that SELECT study has a sound methodology
      and rationale. In lieu of the contrary results of the select study, researchers
      should focus on the probable mechanisms for these contrary findings and continue
      their search for newer and effective agents for prevention of prostate cancer. 

PMID- 25854338
TI  - Prevention of nausea and vomiting: methods and utility after surgery in cancer
      patients?
AB  - Most cancer patients experience nausea and vomiting after surgery. Today, many
      methods of treatment have been developed and used for the control of such
      symptoms. The most important are drug therapy, relaxation, oxygen therapy and gas
      therapy. In addition, dexamethasone, massage therapy and using a Venturi mask
      have also proven effective. Due to the nature of gas consumption which leads to
      nausea it is recommended that use of N2O in the operating room be avoided or
      applied in combination with oxygen or other gases with fewer complications. 

PMID- 25854339
TI  - Predictors of progress in the stage of adoption of breast cancer screening for
      Korean women.
AB  - BACKGROUND: It has been proven that an individuals health behavior is determined
      through a series of processes. This study aimed to assess the stages of adoption
      of breast cancer screening, and to identify the factors relating to progress
      through these stages. MATERIALS AND METHODS: There were 202 female participants
      aged 20- 59 years who were living in Chungbuk, South Korea. They were informed of
      the study purpose and agreed to participate. Data were collected from October
      2010 to January 2011 by assessing the breast cancer screening stage, health
      beliefs, socio-demographic factors, and other facilitating factors. The
      participant current stage of adoption of breast cancer screening was classified
      using the Precaution Adoption Process Model (PAPM), and the various PAPM stages
      were compared with each other to identify factors likely to determine progress
      between stages. The data were analyzed using the chi2-test, ANOVA, Duncan test,
      and multiple logistic regression. RESULTS: Approximately half of all participants
      were not on-schedule for breast self-examination and mammography (unaware, 9.4%
      and 11.4%, unengaged, 8.4% and 5.0%, undecided, 20.3% and 17.8%, decided not to
      act, 1.5% and 1.0%, decided to act, 13.4% and 15.3%, respectively). The factors
      likely to determine the progress from one stage to another were age, marital
      status, exposure to media information about breast cancer, self-efficacy, and
      perceived severity. CONCLUSIONS: These results suggest that it is necessary to
      develop a tailored message for breast cancer screening behavior.

PMID- 25854340
TI  - Predictive and prognostic significance of p27, Akt, PTEN and PI3K expression in
      HER2-positive metastatic breast cancer.
AB  - BACKGROUND: The phosphatidylinositol 3'-kinase/Akt (PI3K/Akt) pathway is a key
      regulator for HER2- overexpressing breast cancer, but data about whether
      activation of PI3K/Akt is associated with poor prognosis and resistance to
      trastuzumab therapy is controversial. In this study we investigated predictive
      and prognostic significance of expression of p27, Akt, PTEN and PI3K, which are
      components of the PI3K/Akt signaling pathway, in HER2-positive metastatic breast
      cancer (MBC), retrospectively. MATERIALS AND METHODS: Fifty-four HER2- positive
      MBC patients who had received first-line trastuzumab-based therapy were recruited
      for the study group. All of the patient's breast tissue samples were examined for
      p27 and Akt expression. In addition, twenty-five patients with sufficient amount
      of tumor tissue were also examined for PTEN and PI3K expression. p27, Akt, PTEN
      and PI3K were evaluated by immunohistochemistry and their relationship with
      patient demographic features, tumor characteristics, response to trastuzumab
      based treatment and survival outcomes were analyzed. RESULTS: p27, Akt, PTEN and
      PI3K were positive in 25.9%, 70.4%, 24% and 96% of the cases, respectively. Nomne
      were significantly associated with response to trastuzumab and time to
      progression (TTP). A trend toward statistical significance for longer overall
      survival (OS) was found for PTEN-positive patients (p=0.058); there was no
      significant relationship between the other immunohistochemical variables and OS.
      When we analyzed groups regarding co-expression, the PTEN-negative/Akt-negative
      group had a significantly lower objective response rate (ORR) (20% vs 80%,
      p=0.023) and the PTEN-negative/p27-negative and PTEN-negative/Akt-negative groups
      had significantly lower median OS compared to other patients (26.4 months vs 76.1
      months, p=0.005 and 25.6 months vs 52.0 months, p=0.007, respectively).
      CONCLUSIONS: p27, Akt, PTEN and PI3K expression is not statistically
      significantly associated with ORR, TTP and OS, individually. However, the
      combined evaluation of p27, Akt and PTEN could be helpful to predict the response
      to trastuzumab-based therapy and prognosis in HER2-positive MBC.

PMID- 25854341
TI  - Nasopharyngeal carcinoma incidence in North Tunisia: negative trends in adults
      but not adolescents, 1994-2006.
AB  - Nasopharyngeal carcinoma (NPC) is the second most common neoplasm of head and
      neck in Tunisia. The distribution is bimodal with a first period occurrence
      between 15 and 20 years old and a second peak at around 50 years of age.
      Undifferentiated carcinoma of nasopharynx type III (UCNT) is the predominant
      histological type (93.4%). Data of cancer registry of North Tunisia confirmed
      that it is an intermediate risk area for NPC with overall ASRs of 3.6 and
      1.6/100,000 respectively in males and females. This study aimed to present the
      evolution of incidence rate of nasopharyngeal carcinoma over a period of 12 years
      (1994-2006). Data of cancer registry of North Tunisia (NTCR), covering half of
      the Tunisian population, were used to determine evolution of NPC incidence,
      calculated by 5 year periods. The estimated annual percentage change (EAPC) was
      used as an estimate of the trend. To best summarize the behavior or the data
      trend across years, we used a join-point regression program. Between 1994 and
      2006, we observed negative annual average change of standardized incidence in men
      and women (-3.3% and -2.7%) also for the standardized incidences which showed a
      rather important decline (26.4% in males and 22.3% in females). The truncated age
      standardized incidence rate of NPC in adults aged of 30 years old and more
      (N=1209) decreased by -0.4% per year from 1994 to 2006 over time in north Tunisia
      dropping from 6.09 to 4.14 person-years. However, the rate was relatively stable
      during this period among youths aged 0-29 years (N=233) in both sexes. NPC
      demonstrated a favorable evolution from 1994-2006 probably due to a improvement
      in socioeconomic conditions.

PMID- 25854342
TI  - Cyr61/CCN1 overexpression induces epithelial-mesenchymal transition leading to
      laryngeal tumor invasion and metastasis and poor prognosis.
AB  - BACKGROUND: To examine the expression of cysteine-rich 61 (Cyr61/CCN1) protein in
      laryngeal squamous- cell carcinoma (LSCC) tissues, and its relationship with the
      tumor epithelial-mesenchymal transition (EMT), invasion, metastasis, and
      prognosis. MATERIALS AND METHODS: Immunohistochemistry was used to detect the
      expressions of Cyr61, Vimentin (Vim), and E-cadherin (E-cad) in 88 cases of LSCC
      tissues and 30 cases of tumor-adjacent normal tissues. Vim and E-cad were used as
      mesenchymal and epithelial markers, respectively, to determine the relationship
      between Cyr61 expression and the EMT of LSCC cells. In addition, clinical and
      histopathological data were combined to analyze the relationship between the
      positive-expression rates of Cyr61, Vim and E-cad and LSCC invasion, metastasis
      and prognosis. RESULTS: In LSCC tissues, Vim expression rate was significantly
      higher than that of the tumor-adjacent tissues, whereas E-cad expression rate was
      significantly lower than that of the tumor-adjacent tissues. The Vim expression
      rate was significantly higher in stages T3 and T4 than in stages T1 and T2 LSCC
      tissues, whereas E-cad expression rate was significantly lower in stages T3 and
      T4 than in stages T1 and T2 LSCC tissues. Compared to the group without lymph
      node metastasis, the Vim expression rate was significantly higher and the E-cad
      expression rate was significantly lower in the group with lymph node metastasis.
      The expression rate of Cyr61 was significantly higher in LSCC tissues than in the
      tumor-adjacent normal tissues. In addition, the Cyr61 expression rate was higher
      in stages T3 and T4 than in stages T1 and T2 LSCC, and higher in the group with
      lymph node metastasis than in the group without lymph node metastasis. The Vim
      expression rate was significantly higher in the Cyr61 positive group than in the
      Cyr61 negative group, whereas the E-cad expression rate was significantly higher
      in the Cyr61 negative group than in the Cyr61 positive group. Survival analysis
      indicated that survival rates of Cyr61 positive, Vim positive and E-cad negative
      groups were significantly lower than that of Cyr61 negative, Vim negative and E
      cad positive groups, respectively. CONCLUSIONS: Cyr61 expression is closely
      associated with LSCC invasion and lymph node metastasis. Overexpression of Cyr61
      may induce EMT and therefore leads to LSCC invasion and metastasis and poor
      prognosis. Cyr61 may become a new maker for clinical prediction of LSCC invasion
      and metastasis and a new target for LSCC treatment.

PMID- 25854343
TI  - Tumor-derived CD4+CD25+ Tregs inhibit the maturation and antigen-presenting
      function of dendritic cells.
AB  - CD4+CD25+regulatory T cells (Tregs) play a key role in regulation of immnue
      response and maintenance of self-tolerance. Studies have found Tregs could
      suppress tumor-specific T cell-mediated immune response and promote cancer
      progression. Depletion of Tregs can enhance antitumor immunity. Dendritic cells
      (DCs) are professional antigen-presenting cells and capable of activating antigen
      specific immune responses, which make them ideal candidate for cancer
      immunotherapy. Now various DC vaccines are considered as effective treatment for
      cancers. The aim of this study was to evaluate variation of Tregs in BALB/C mice
      with hepatocellular carcinoma and investigate the interaction between tumor
      derived Tregs, effector T cells (Teff) and splenic DCs. We found the percentages
      of Tregs/CD4+ in the peripheral blood of tumor-bearing mice were higher than in
      normal mice. Tumor-derived Tregs diminished the up-regulation of costimulatory
      molecule expression on splenic DCs, even in the presence of Teff cells and
      simultaneously inhibited IL-12 and TNF-alpha secretion by DCs. 

PMID- 25854344
TI  - Mean platelet volume could be a possible biomarker for papillary thyroid
      carcinomas.
AB  - Thyroid cancer is the most prevalent endocrine cancer and is evident in nearly 5%
      of thyroid nodules. The correlation between mean platelet volume (MPV) and many
      other cancer types has been investigated previously. However, the correlation
      between papillary thyroid carcinoma (PTC) and MPV has not yet been studied in
      detail. The aim of this study was to examine whether MPV would be a useful
      inflammatory marker to differentiate PTC patients from cases of benign goiter and
      healthy controls. Preoperative MPV levels in patients with PTC were found to be
      significantly higher when compared with benign goiter patients and healthy
      controls ((respectively, 8.05 femtoliter (fl), 7.57 fl, 7.36 fl, p=0.001). After
      surgical treatment of PTC patients, a significant decrease in MPV levels was seen
      (8.05 fl versus 7.60 fl, p=0.005). ROC analysis suggested 7.81 as the cut-off
      value for MPV (AUC=0.729, sensitivity 60%, specificity 80%). In conclusion, maybe
      changes in MPV levels can be used as an easily available biomarker for monitoring
      the risk of PTC in patients with thyroid nodules, enabling early diagnosis of
      PTC. 

PMID- 25854345
TI  - Intrinsic tumour factors affecting recurrence in non muscle invasive bladder
      cancer: a hospital based study from India.
AB  - BACKGROUND: Depending on various pathological factors, non muscle invasive
      bladder cancer (NMIBC) shows varying degrees of recurrence. The aim of this study
      was to determine the incidence of recurrence of NMIBS in our centre, study the
      influence of intrinsic tumour characteristics like grade, stage, size and number,
      and compare our results with data in the published literature. MATERIALS AND
      METHODS: A hospital based retrospective study was conducted on patients who
      underwent treatment for NMIBC from 2011 to 2014. The factors studied were number,
      size, grade, stage and site for correlation with recurrence. Statistical analysis
      was performed using Medcalc version 12, using Pearson's Chi square test to
      ascertain associations between variables. RESULTS: A total of 73 patients with
      NMIBC were studied of which 48 (65.8%) had low grade and 25 (34.2%) had high
      grade tumours. Some 38 patients (52.1%) had Ta tumours, 34 (46.6%) had T1 and one
      had CIS. Mean follow up was 34.3 months. Recurrence rates were found to be 33.3%
      in low grade and 52.0% in high grade tumours. The overall recurrence rate in our
      centre was 39.7%. Significant correlations were seen between stage and
      recurrence, with a rate of 15% for Ta and 63.3% for T1 tumours. Fourteen out of
      21 bladder cancers (66.6%) with multiple tumours demonstrated recurrence
      (p=0.006). Grade, size and site had no influence. CONCLUSIONS: In our study,
      recurrence of NMIBC was found to be directly proportional to stage and number of
      primary tumours, but not grade, size and site. The incidence of recurrence of
      NMIBC both stage wise and grade wise in our centre was also low compared to the
      data in the published literature.

PMID- 25854346
TI  - Inhibitory effect of phenethyl isothiocyanate against benzo[a] pyrene-induced
      rise in CYP1A1 mRNA and apoprotein levels as its chemopreventive properties.
AB  - BACKGROUND: Phenethyl isothiocyanate (PEITC), the most comprehensively studied
      aromatic isothiocyanate, has been shown to act as an anti-cancer agent mainly
      through modulation of biotransformation enzymes responsible for metabolizing
      carcinogens in the human body. Humans are often exposed to carcinogenic factors,
      some of which through the diet, such as polycyclic aromatic hydrocarbon
      benzo[a]pyrene via the consumption of over-cooked meats. Inhibition of the
      enzymes responsible for the bioactivation of this carcinogen, for example CYP1A1,
      the major enzyme required for polycyclic aromatic hydrocarbons (PAHs)
      bioactivation, is recognized as a chemoprevention strategy. OBJECTIVE: To
      evaluate the inhibitory effects of PEITC against benzo[a]pyrene-induced rise in
      rat liver CYP1A1 mRNA and apoprotein levels. MATERIALS AND METHODS: Precision cut
      rat liver slices were treated with benzo[a]pyrene at 1 and 5 MUM in the presence
      of PEITC (1-25 MUM) for 24 hours, followed by determination of CYP1A1 mRNA and
      apoprotein levels using quantitative polymerase chain reaction and
      immunoblotting. RESULTS: Findings revealed that PEITC inhibited benzo[a]pyrene
      induced rise in rat liver CYP1A1 mRNA in a dose-dependent manner as well as the
      apoprotein levels of CYP1A. CONCLUSIONS: It was demonstrated that PEITC can
      directly inhibit the bioactivation of benzo[a]pyrene, indicating chemopreventive
      potential.

PMID- 25854347
TI  - Preoperative serum CEA and CA19-9 in gastric cancer--a single tertiary hospital
      study of 1,075 cases.
AB  - To evaluate the clinical impact of preoperative serum CEA and CA19-9 on
      resectable gastric cancer (GC), a total of 1,075 consecutive cases with gastric
      adenocarcinoma were obtained retrospectively from January 2012 and December 2013
      in a single tertiary hospital, and the relationships between serum CEA, CA19-9
      and clinicopathologic features were investigated. Positive preoperative serum
      rates of CEA and CA19-9 were 22.4% and 12.3% respectively, levels significantly
      correlating with each other and depth of invasion, lymph node involvement, pTNM
      and stage. The CEA level also presented a remarkable association with
      lymphovascular invasion. Both CEA and CA19-9 positivity significantly and
      positively correlated with depth of invasion, nodal involvement, pTNM stage,
      lymphovascular invasion, tumor size and tumor location. Stratified analyses
      according to gender or tumor location showed preoperative CEA or CA19-9 had
      different associations with clinicopathologic features in different gender
      subgroups or location subgroups. Preoperative serum CA19-9 positivity may be more
      meaningful for tumor size rather than CEA. In conclusion, preoperative serum CEA
      and CA19-9 correlate with disease progression of GC, and may have applications in
      aiding more accurate estimation of tumor stage, decision of treatment choice and
      prognosis evaluation. 

PMID- 25854348
TI  - Diagnosis value of membrane glycolipids biochemistry index in intracranial and
      gastrointestinal tumors.
AB  - The diagnostic value of membrane glycolipid biochemistry index, the lipid-bound
      sialic acid (LSA) and total sialic acid (TSA) in cerebrospinal fluid (CSF) was
      evaluated in 30 intracranial and 65 gastrointestinal tumors. The plasma LSA, TSA
      and red cell membrane sialic acid (R-SA) in were determined according to the
      method of Sevenmerhulm. Our results showed that the levels of LSA and TSA in CSF
      of intracranial tumor patients was higher than that of normal group(p<0.01). The
      concentration of TSA and LSA in patients with malignant glioma was higher than
      that of benign meningioma patients(P<0.01). No significance was found between
      intracranial halmatoma patients and normal control group for levels of membrane
      glycolipids (p>0.05). Results also found that the plasma LSA, TSA and R-SA of
      gastric carcinoma were significantly higher than those of control group (p<0.05);
      while no significant difference was found in the plasma LSA, TSA and R-SA levels
      between chronic gastritis, gastrohelcoma and normal control group (p>0.05).
      Plasma LSA, TSA and R-SA levels of gastric carcinoma patient were significantly
      higher than those of chronic gastritis patients and gastrohelcoma
      patients(p<0.05). It was also found that plasma LSA, TSA and R-SA contents were
      significantly higher in large intestine carcinoma patients than in benign in
      stestine tumor patients (p<0.05) while no significant difference was found
      between intestine benign tumor and normal control group (p>0.05). The levels of
      LSA, TSA and R-SA were obviously higher in the patients with metastasis than in
      the ones without (p<0.05.) The membrane glycolipid biochemistry index LSA and TSA
      in CSF are sensive markers for diagnosing intracranial tumors. For
      gastrointestinal malignant tumors the plasma LSA TSA and red blood cell membrane
      SA may be considered as auxiliary indicators for diagnosis. They can be used for
      distinguishing benign from malignant tumors. 

PMID- 25854349
TI  - Assessment of perception of medical students in regard to links between tobacco
      or alcohol use and cancer.
AB  - BACKGROUND: The aim of this study was to assess cancer awareness among medical
      students in Saudi Arabia toward tobacco and alcohol use as risk factors.
      MATERIALS AND METHODS: A cross-sectional survey from October to December 2014,
      covering 1200 medical students, was performed. RESULTS: Of the total, 975
      (81.25%) responded. The male to female ratio was 1.00:7.125. 96/975 (9.8%) had
      smoked tobacco in their lifetime, and 51/975 (5.23%) were alcoholic beverage
      consumers. On asking them whether tobacco smoking and alcohol consumption can
      cause cancer, only 4/975 (0.4%) and 14/975 (1.43%) answered no for smoking and
      alcohol, respectively. CONCLUSIONS: The prevalence of smoking and alcohol use is
      very low among medical students, which might be due to high female contribution
      besides social stigma. The prevalence of second-hand smoke (SHS) was found to be
      very high in Hail region.

PMID- 25854350
TI  - Effect of pulsed electromagnetic field on MMP-9 and TIMP-1 levels in
      chondrosarcoma cells stimulated with IL-1beta.
AB  - Chondrosarcoma, the second most common type of bone malignancy, is characterized
      by distant metastasis and local invasion. Previous studies have shown that
      treatment by pulsed electromagnetic field (PEMF) has beneficial effects on
      various cancer cells. In this study, we investigated the effects of PEMF applied
      for 3 and 7 days on the matrix metalloproteinase (MMP) levels in chondrosarcoma
      SW1353 cells stimulated with two different doses of IL-1beta. SW1353 cells were
      treated with (0.5 and 5 ng/ml) IL-1beta and PEMF exposure was applied either 3 or
      7 days. MMP-9 and TIMP-1 levels were measured in conditioned media by enzyme
      linked immunosorbent assay. The results were relative to protein levels.
      Statistical analyses were performed using one-way analysis of variance (ANOVA).
      P<0.05 was considered significant. PEMF treatment significantly decreased MMP-9
      protein levels in human chondrosarcoma cells stimulated with 0.5 ng/ml IL-1beta
      at day 7, whereas it did not show any effect on cells stimulated with 5 ng/ml IL
      1beta. There was no significant change in TIMP-1 protein levels either by IL
      1beta stimulation or by PEMF treatment. The results of this study showed that
      PEMF treatment suppressed IL-1beta-mediated upregulation of MMP-9 protein levels
      in a dual effect manner. This finding may offer new perspectives in the therapy
      of bone cancer. 

PMID- 25854351
TI  - Role of the MDM2 promoter polymorphism (-309T>G) in acute myeloid leukemia
      development.
AB  - BACKGROUND: The human homologue of the mouse double minute 2 (MDM2) gene is a
      negative regulator of Tp53. MDM2-309T>G a functional promoter polymorphism was
      found to be associated with overexpression thereby attenuation of Tp53 stress
      response and increased cancer susceptibility. We have planned to evaluate the
      possible role of MDM2-309T>G polymorphism with risk and response to chemotherapy
      in AML. MATERIALS AND METHODS: A total of 223 de novo AML cases and 304 age and
      sex matched healthy controls were genotyped for the MDM2-309T>G polymorphism
      through the tetra-primer amplification refractory mutation system (ARMS)-PCR
      method. In order to assess the functional relationship of -309T>G SNP with MDM2
      expression level, we quantified MDM2 mRNA in 30 primary AML blood samples through
      quantitative RT-PCR. Both the (-309T>G) genotypes and the MDM2 expression were
      correlated with disease free survival (DFS) rates among patients who have
      achieved complete remission (CR) after first induction chemotherapy. RESULTS:
      MDM2-309T>G polymorphism was significantly associated with AML development
      (p<0.0001). The presence of either GG genotype or G allele at MDM2-309 confered
      1.79 (95% CI: 1.12-2.86; p<0.001) and 1.46 fold (95%CI: 1.14-1.86; p=0.003)
      increased AML risk. Survival analysis revealed that CR+ve cases with GG genotype
      had significantly increased DFS rates (16months, p=0.05) compared to CR+ve TT (11
      months) and TG (9 months) genotype groups. Further, MDM2 expression was also
      found to be significantly elevated in GG genotype patients (p=0.0039) and among
      CR+ve cases (p=0.0036). CONCLUSIONS: The MDM2-309T>G polymorphism might be
      involved in AML development and also serve as a good prognostic indicator.

PMID- 25854352
TI  - Meta-analysis of the association between the rs8034191 polymorphism in AGPHD1 and
      lung cancer risk.
AB  - BACKGROUND: Possible associations between the single nucleotide polymorphism
      (SNP) rs8034191 in the aminoglycosidephosphotransferase domain containing 1
      (AGPHD1) gene and lung cancer risk have been studied by many researchers but the
      results have been contradictory. MATERIALS AND METHODS: A computerized search for
      publications on rs8034191 and lung cancer risk was performed. Odds ratios (ORs)
      with 95% confidence intervals (CIs) were calculated to assess the association
      between rs8034191 and lung cancer risk with 13 selected case-control studies.
      Sensitivity analysis, test of heterogeneity, cumulative meta-analysis, and
      assessment of bias were also performed. RESULTS: A significant association
      between rs8034191 and lung cancer susceptibility was found using the dominant
      genetic model (OR=1.344, 95% CI: 1.285-1.406), the additive genetic model
      (OR=1.613, 95% CI: 1.503-1.730), and the recessive genetic model (OR=1.408, 95%
      CI: 1.319-1.503). Moreover, an increased lung cancer risk was found with all
      genetic models after stratification of ethnicity. CONCLUSIONS: The association
      between rs8034191 and lung cancer risk was significant using multiple genetic
      models, suggesting that rs8034191 is a risk factor for lung cancer. Further
      functional studies of this polymorphism and lung cancer risk are warranted.

PMID- 25854353
TI  - Identification of ANXA1 as a lymphatic metastasis and poor prognostic factor in
      pancreatic ductal adenocarcinoma.
AB  - OBJECTIVE: The aim of this study was to investigate the clinical significance of
      annexin a1 (ANXA1) and provide molecular evidence to support that decreased ANXA1
      expression could enhance cancer migration and invasion in pancreatic ductal
      adenocarcinoma (PDAC). MATERIALS AND METHODS: Immunohistochemistry of a tissue
      microarray with 162 surgically resected PDAC specimens was performed to examine
      the expression of ANXA1. We also investigated the relationship between ANXA1
      expression and clinicopathological factors and prognosis of PDAC patients. We
      further studied the role of ANXA1 in PDAC cell proliferation, migration and
      invasion by cell proliferation assay, migration assay and matrigel invasion assay
      with reduced ANXA1 expression by RNAi. Western blotting was used to detect matrix
      metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinase-1 (TIMP-1)
      expression. We also detected MMP-9 enzyme activity by gelatin zymography.
      RESULTS: Decreased expression of ANXA1 was significantly associated with poor
      differentiation, lymph node metastasis and advanced TNM stage of PDAC patients
      (p<0.05). Moreover, decreased expression of ANXA1 was correlated with poor
      survival (p<0.05). Furthermore, we found that ANXA1 knockdown inhibited cell
      proliferation, induced G1 phase cell cycle arrest, increased PDAC cell migration
      and invasion capacity compared with controls. In addition, Western blotting
      showed that ANXA1 knockdown increased the MMP-9 protein level and decreased TIMP
      1 expression. Gelatin zymography showed that MMP-9 enzyme activity was also
      elevated. CONCLUSIONS: Negative ANXA1 expression is a most unfavorable prognostic
      factor for PDAC patients. ANXA1 knockdown inhibits cell proliferation by inducing
      G1 phase cell cycle arrest and increases migration and invasion of PDAC cells
      through up-regulating MMP-9 expression and activity, implying that ANXA1 may
      serve as a promising prognostic biomarker and therapeutic target for PDAC.

PMID- 25854354
TI  - S100A12 and RAGE expression in human bladder transitional cell carcinoma: a role
      for the ligand/RAGE axis in tumor progression?
AB  - BACKGROUND: Transitional cell carcinoma (TCC) and prostate cancer are the most
      frequent cancers in the male genitourinary tract. Measurement of biological
      biomarkers may facilitate clinical monitoring and aid early diagnosis of TCC. The
      aim of the present investigation was to detect the mRNA levels of S100A12 and
      RAGE (receptor for advanced glycation end products) in patients suffering from
      bladder TCC. MATERIALS AND METHODS: To explore the involvement of S100A12 and
      RAGE genes, total RNA was harvested from cancer tissues and samples obtained from
      normal non-tumorized urothelium of the same patients. Quantitative PCR (qPCR) was
      subsequently employed to determine the mRNA levels of S100A12 and RAGE. RESULTS:
      The results showed that mRNA expression of S100A12 and RAGE was significantly up
      regulated in the cancer tissue. CONCLUSIONS: According to the results presented
      in the current study, mRNA expression of S100A12 and RAGE might be as a useful
      biomarker for TCC. Therefore, this ligand-receptor axis possibly plays important
      roles in the development of TCC and may serve either as an early diagnostic
      marker or as a key factor in monitoring of response to treatment. More research
      is required concerning inhibition of the S100A12-RAGE axis in different cancer
      models.

PMID- 25854355
TI  - Public awareness of warning signs and symptoms of cancer in oman: a community
      based survey of adults.
AB  - BACKGROUND: The majority of deaths from cancer occur in low and middle income
      countries, partly due to poor public awareness of the signs and symptoms of
      cancer. MATERIALS AND METHODS: A community based survey using the Cancer
      Awareness Measure (CAM) questionnaire was conducted in three different
      communities in Oman. Omani adults aged 18 years and above were invited to
      participate in the study. RESULTS: A total of 345 responded from 450 invited
      participants (response rate=76.7%). The majority of respondents were unable to
      identify the common signs and symptoms of cancer identified in the CAM (average
      awareness was 40.6%). The most emotional barrier to seeking help was worry about
      what the doctor might find (223, 64.6%); a practical barrier was too busy to make
      an appointment (259, 75.1%) and a service barrier was difficulty talking to the
      doctor (159, 46.1%). The majority of respondents (more than 60% for seven out of
      ten symptoms) would seek medical help in two weeks for most signs or symptoms of
      cancer. Females were significantly more likely than males to be embarrassed
      (p<0.001), scared (p=0.001), and lack confidence talking about their symptoms
      (p=0.022). CONCLUSIONS: Urgent strategies are needed to improve public awareness
      of the signs and symptoms of cancer in Oman. This might leads to earlier
      diagnosis, improved prognosis and reduced mortality from cancer.

PMID- 25854356
TI  - Assessing activity limitation among cancer survivors in Korea using data from a
      nationwide survey.
AB  - BACKGROUND: More than 1 million cancer survivors reside in Korea. We here
      investigated activity limitations of cancer survivors compared to controls
      without a history of cancer. MATERIALS AND METHODS: Using the 4th and 5th Korea
      National Health and Nutrition Examination Survey (2007-2012) data, we identified
      1,155 adult cancer survivors. Activity limitations were defined as limitation in
      activities of daily living, experience of lying in a sickbed, and number of days
      lying in a sickbed during the last month. Descriptive analysis and multiple
      logistic regression compared these measures for survivors and controls by sex and
      age groups. RESULTS: Approximately 29.4% of cancer survivors reported limitation
      in activities of daily living, 14.6% experienced lying in a sickbed, and 4.3%
      experienced more than 15 days lying in a sickbed during the last month. After
      controlling for demographic and health-related factors, cancer survivors were
      more likely to report activity limitation than controls. The associations were
      similar across sex and age groups. CONCLUSIONS: Cancer survivors have increased
      activity limitation compared to controls and these limitations persist across sex
      and age. Targeted interventions and improved management are essential for
      improving cancer survivor daily life.

PMID- 25854357
TI  - PLCE1 gene in esophageal cancer and interaction with environmental factors.
AB  - OBJECTIVE: To study the PLCE1 gene rs2274223 polymorphism with regard to
      esophageal cancer and its interaction with diet, lifestyle, psychological and
      environmental factors in Southwest Shandong province. MATERIALS AND METHODS: A
      case series study (case-case) was conducted. Questionnaire data were collected
      and 3 ml-5 ml venous blood was drawn for DNA extraction among the qualified
      research subjects. PLCE1 gene polymorphism was detected after PCR amplification
      of DNA. SPSS 13.0 software was used for statistical analysis of the data.
      RESULTS: The three genotypes A/A, A/G and G/G PLCE1 gene rs2274223 was 31, 16 and
      4 cases, accounting for 60.8%, 31.4%, 0.08% respectively. The difference of three
      genotypes (AA/GA/GG) proportion between negative and positive family history of
      patients was statistically significant, chi2=6.213, p=0.045. There was no
      statistically significant relationship between PLCE1 gene rs2274223 polymorphism
      and smoking, drinking, chi2=0.119, p=0.998, and chi2=1.727, p=0.786. There was no
      linkage of the three rs2274223 PLCE1 gene genotypes (AA/GA/GG) proportion with
      eating fried, pickled, hot, mildew, overnight, smoked, excitant food, eat speed,
      salt taste or not (p>0.05). or with living environment pollution and nine risk
      factors of occupational exposure (p>0.05). There was no statistically significant
      difference in TS scores between different genotype of rs2274223 PLCE1 gene.
      CONCLUSIONS: The PLCE1 rs2274223 polymorphism has a relationship with family
      history of esophageal cancer, but does not have any significant association with
      age, gender, smoking, alcohol drinking, food hygiene, eating habits, living
      around the environment and occupation in cases.

PMID- 25854358
TI  - TRAIL suppresses human breast cancer cell migration via MADD/CXCR7.
AB  - BACKGROUND: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can
      specifically induce apoptosis limited to various cancer cells, so this reagent is
      considered a promising medicine for cancer therapy. TRAIL also exerts effects on
      non-apoptotic signals, relevant to processes such as metastasis, autophagy and
      proliferation in cancer cells. However, the mechanisms of TRAIL-regulated non
      apoptotic signals are unclear. The purpose of this study was to investigate
      MADD/CXCR7 effects in TRAIL-mediated breast cancer cell migration. MATERIALS AND
      METHODS: The ability of MADD/CXCR7 to regulate MVP signaling in TRAIL-mediated
      breast cancer cells migration was evaluated by transwell migration assay,
      quantitative RT-PCR, Western blotting and knock down experiments. RESULTS: In
      this study, we found that treatment with TRAIL resulted in induced expression
      levels of MADD and CXCR7 in breast cancer cells. Knock down of MADD followed by
      treatment with TRAIL resulted in increased cell migration compared to either
      treatment alone. Similarly, through overexpression and knockdown experiments, we
      demonstrated that CXCR7 also positively regulated TRAIL- inhibited migration.
      Surprisingly, knock down of MADD lead to inhibition of TRAIL-induced CXCR7 mRNA
      and protein expression and overexpression of CXCR7 lead to the reduction of MADD
      expression, indicating that MADD is an upstream regulatory factor of TRAIL
      triggered CXCR7 production and a negative feedback mechanism between MADD and
      CXCR7. Furthermore, we showed that CXCR7 is involved in MADD-inhibited migration
      in breast cancer cells. CONCLUSIONS: Our work defined a novel signaling pathway
      implicated in the control of breast cancer migration.

PMID- 25854359
TI  - Epidemiology characteristics and trends of incidence and morphology of stomach
      cancer in Iran.
AB  - BACKGROUND: Stomach cancer is the fourth most common cancer and the second
      leading cause of cancer- related death through the world. It is predicted that
      the number of new cancer cases will be more than 15 million cases by 2020.
      Regarding the lack of studies on this topic in the country, we have thoroughly
      examined the patho-epidemiology of stomach cancer in Iran. MATERIALS AND METHODS:
      In this cross- sectional study data were collected retrospectively reviewing all
      new stomach cancer patients in Cancer Registry Center report of health deputy for
      Iran during a 6-year period (2003-2008). The study also examined the morphology
      of common stomach cancers. Trends in incidence and morphology underwent joinpoint
      regression analysis. RESULTS: During the six-year period, a total of 35,171 cases
      of stomach cancer were registered. Average age standardized rate for females and
      males were equal to 7.1 and 15.1 per 100,000 persons, respectively. Most common
      histological type was adenocarcinoma, NOS with 21,980 cases (62.50%). The annual
      percentage change (APC) in age-standardized incidence rate (per 100,000) was
      increase in both females and males at 11.1 (CI: 4.3 to 18.3) and 9.2 (CI: 5.2 to
      13.4), respectively. CONCLUSIONS: According to our results, the incidence of
      gastric cancer is increasing in Iran, so further epidemiological studies into the
      etiology and early detection are essential.

PMID- 25854360
TI  - Antioxidant, anticancer and anticholinesterase activities of flower, fruit and
      seed extracts of Hypericum amblysepalum HOCHST.
AB  - BACKGROUND: Cancer is an unnatural type of tissue growth in which the cells
      exhibit unrestrained division, leading to a progressive increase in the number of
      dividing cells. It is now the second largest cause of death in the world. The
      present study concerned antioxidant, anticancer and anticholinesterase activities
      and protocatechuic, catechin, caffeic acid, syringic acid, p-coumaric acid and o
      coumaric concentrations in methanol extracts of flowers, fruits and seeds of
      Hypericum amblysepalum. MATERIALS AND METHODS: Antioxidant properties including
      free radical scavenging activity and reducing power, and amounts of total
      phenolic compounds were evaluated using different tests. Protocatechuic,
      catechin, caffeic acid, syringic acid, p-coumaric acid and o-coumaric
      concentrations in extracts were determined by HPLC. Cytotoxic effects were
      determined using the MTT test with human cervix cancer (HeLa) and rat kidney
      epithelium cell (NRK-52E) lines. Acetyl and butyrylcholinesterase inhibitory
      activities were measured by by Ellman method. RESULTS: Total phenolic content of
      H. amblysepalum seeds was found to be higher than in fruit and flower extracts.
      DPPH free radical scavenging activity of the obtained extracts gave satisfactory
      results versus butylated hydroxyanisole and butylated hydroxytoluene as controls.
      Reducing power activity was linearly proportional to the studied concentration
      range: 10-500 MUg/ mL LC50 values for H. amblysepalum seeds were 11.7 and 2.86
      respectively for HeLa and NRK-52E cell lines. Butyryl-cholinesterase inhibitory
      activity was 76.9+/-0.41 for seed extract and higher than with other extracts.
      CONCLUSIONS: The present results suggested that H. amblysepalum could be a
      potential candidate anti-cancer drug for the treatment of human cervical cancer,
      and good source of natural antioxidants.

PMID- 25854361
TI  - Association between ABO genotype and risk of hepatocellular carcinoma in Koreans.
AB  - BACKGROUND: Associations between ABO blood groups and risk of several
      malignancies have been reported, although there are limited data regarding
      hepatocellular carcinoma (HCC). The aim of this study was to investigate any
      possible association between the ABO genotype, especially blood group A, and HCC
      risk in Koreans. MATERIALS AND METHODS: We conducted a case-control study of
      1,538 patients with newly diagnosed HCC at Chonnam National University Hwasun
      Hospital and 1,305 randomly selected members of the general population. The ABO
      genotype was determined by multicolor real-time polymerase chain reaction (PCR)
      using displacing probes. Adjusted odds ratios (aORs) and their 95% confidence
      intervals (CIs) were calculated using logistic regression models with adjustment
      for gender, age, smoking, alcohol drinking, and hepatitis B and C status.
      RESULTS: The risk of HCC in genotype AA was significantly higher than in OO
      (aOR=1.773, 95% CI=1.161-2.705). The risk in blood group A was also higher than
      in blood group O (aOR=1.448, 95% CI=1.005 1.897). No significant difference was
      found for the AA, BO, BB, and AB genotypes, or blood group B and AB. CONCLUSIONS:
      Blood group A and genotype AA showed the highest risks of HCC in a Korean
      population. No significant difference was found for the AO, BO, BB, and AB
      genotypes, or blood group B and AB.

PMID- 25854362
TI  - Correlation of overexpression of nestin with expression of epithelial-mesenchymal
      transition-related proteins in gastric adenocarcinoma.
AB  - BACKGROUND: Nestin is associated with neoplastic transformation. However, the
      mechanisms by which nestin contributes regarding invasion and malignancy of
      gastric adenocarcinoma (GAC) remain unknown. Recent studies have shown that the
      epithelial-mesenchymal transition (EMT) is important in invasion and migration of
      cancer cells. In the present study, we aimed to investigate the expression of
      nestin and its correlation with EMT-related proteins in GAC. MATERIALS AND
      METHODS: The expression of nestin and EMT-related proteins was examined in GAC
      specimens and cell lines by immunohistochemistry and Western blotting.
      Clinicopathological features and survival outcomes were retrospectively analyzed.
      RESULTS: Positive nestin immunostaining was most obviously detected in the
      cytoplasm, nucleus or both cytoplasm and nucleus of tumor cells in 19.2% (24/125)
      of GAC tissues, which was significantly higher than that in normal gastric mucosa
      tissues (1.7%, 1/60) (p=0.001). Nestin expression was closely related to several
      clinicopathological factors and EMT-related proteins (E-cadherin, vimentin and
      Snail) and displayed a poor prognosis. Interestingly, simultaneous cytoplasmic
      and nuclear nestin expression correlated with EMT-related proteins (E-cadherin,
      vimentin and Snail) (p<0.05) and lymph node metastasis (p=0.041) and a shorter
      survival time (p<0.05), but this was not the case with cytoplasmic or nuclear
      nestin expression. CONCLUSIONS: Nestin, particularly expression in both cytoplasm
      and nucleus, might be involved in regulating EMT and malignant progression in
      GAC, with potential as an unfavorable indicator in tumor diagnosis and a target
      for clinical therapy.

PMID- 25854363
TI  - Effect of autophagy-related beclin1 on sensitivity of cisplatin-resistant ovarian
      cancer cells to chemotherapeutic agents.
AB  - The purpose of the study was to determine the effects of autophagy related gene
      Beclin1 at different levels of expression on the sensitivity of cisplatin
      resistant ovarian cancer cells (SKOV3/DDP) to different chemotherapeutics. In
      pSUPER-Beclin1 transfected cells, real-time fluorescence quantitative RT-PCR and
      Western blot analysis showed that expression was significantly inhibited. Flow
      cytometry revealed that the mean fluorescence intensity (MDC), reflecting
      autophagy, and cells in the G0/G1 phase were markedly reduced. When compared with
      the blank control group, inhibition of Beclin1 expression in SKOV3/DDP cells not
      only increased the rate of apoptosis following treatment with chemotherapeutics,
      but also increased the sensitivity. These findings suggest that Beclin1
      expression plays an important role in chemotherapeutic agent-induced death of
      SKOV3/DDP cells. Inhibition of autophagy related gene Beclin1 expression in
      SKOV3/DDP cells may increase the rate of apoptosis and elevate the sensitivity to
      chemotherapeutics. 

PMID- 25854364
TI  - Integrative meta-analysis of multiple gene expression profiles in acquired
      gemcitabine-resistant cancer cell lines to identify novel therapeutic biomarkers.
AB  - In molecular-targeted cancer therapy, acquired resistance to gemcitabine is a
      major clinical problem that reduces its effectiveness, resulting in recurrence
      and metastasis of cancers. In spite of great efforts to reveal the overall
      mechanism of acquired gemcitabine resistance, no definitive genetic factors have
      been identified that are absolutely responsible for the resistance process.
      Therefore, we performed a cross-platform meta-analysis of three publically
      available microarray datasets for cancer cell lines with acquired gemcitabine
      resistance, using the R-based RankProd algorithm, and were able to identify a
      total of 158 differentially expressed genes (DEGs; 76 up- and 82 down-regulated)
      that are potentially involved in acquired resistance to gemcitabine. Indeed, the
      top 20 up- and down-regulated DEGs are largely associated with a common process
      of carcinogenesis in many cells. For the top 50 up- and down-regulated DEGs, we
      conducted integrated analyses of a gene regulatory network, a gene co-expression
      network, and a protein-protein interaction network. The identified DEGs were
      functionally enriched via Gene Ontology hierarchy and Kyoto Encyclopedia of Genes
      and Genomes pathway analyses. By systemic combinational analysis of the three
      molecular networks, we could condense the total number of DEGs to final seven
      genes. Notably, GJA1, LEF1, and CCND2 were contained within the lists of the top
      20 up- or down-regulated DEGs. Our study represents a comprehensive overview of
      the gene expression patterns associated with acquired gemcitabine resistance and
      theoretical support for further clinical therapeutic studies. 

PMID- 25854365
TI  - Effects of perceived smoking-cancer relationship and cardiovascular health
      attitudes on childrens' views of smoking.
AB  - BACKGROUND: This study was conducted with the aim of determining how students'
      perceived smoking-cancer relationship and cardiovascular health attitudes affect
      childrens' views of smoking. MATERIALS AND METHODS: The sample of this
      descriptive-cross sectional study comprised 574 subjects between the ages of 11
      15. The data were collected using the Children's Cardiovascular Health Promotion
      Attitude Scale and the Children's Decisional Balance Measure for Assessing and
      Predicting Smoking Status. Correlation and logistic regression were used for
      analysis. RESULTS: It was determined that a statistically significant
      relationship exists between the attitudes of children towards smoking and their
      ideas about the relationship of smoking with cancer, which is negative and low
      (r=-0.223). There was also a statistically significant relationship between their
      attitudes towards cardiovascular health and their attitudes towards smoking,
      again at a low level (r=0.257). It was determined that children with ideas about
      smoking and cancer were 9.4 times less likely to have positive/negative attitudes
      towards smoking, while positive attitudes towards cardiovascular health made
      negative attitudes towards smoking 3.9 times less likely. CONCLUSIONS: It was
      determined that the attitudes of students towards cardiovascular health and their
      perceptions of smoking and cancer reduced the positive perceptions towards
      smoking.

PMID- 25854366
TI  - BmKn-2 scorpion venom peptide for killing oral cancer cells by apoptosis.
AB  - Scorpion venom peptides recently have attracted attention as alternative
      chemotherapeutic agents that may overcome the limitations of current drugs,
      providing specific cytotoxicity for cancer cells with an ability to bypass
      multidrug-resistance mechanisms, additive effects in combination therapy and
      safety. In the present study, BmKn-2 scorpion venom peptide and its derivatives
      were chosen for assessment of anticancer activities. BmKn-2 was identified as the
      most effective against human oral squamous cells carcinoma cell line (HSC-4) by
      screening assays with an IC50 value of 29 MUg/ml. The BmKn-2 peptide killed HSC-4
      cells through induction of apoptosis, as confirmed by phase contrast microscopy
      and RT-PCR techniques. Typical morphological features of apoptosis including cell
      shrinkage and rounding characteristics were observed in treated HSC-4 cells. The
      results were further confirmed by increased expression of pro-apoptotic genes
      such as caspase-3, -7, and -9 but decrease mRNA level of anti-apoptotic BCL-2 in
      BmKn-2 treated cells, as determined by RT-PCR assay. In summary, the BmKn-2
      scorpion venom peptide demonstrates specific membrane binding, growth inhibition
      and apoptogenic activity against human oral cancer cells. 

PMID- 25854367
TI  - Inhibitory effect of curcumin on invasion of skin squamous cell carcinoma A431
      cells.
AB  - OBJECTIVE: To investigate the regulatory effect of curcumin on expression of
      signal transducer and activator of transcription 3 (STAT3) in skin squamous cell
      carcinoma tissues as well as possible mechanisms of curcumin in prevention and
      treatment of skin squamous cell carcinoma. MATERIALS AND METHODS: Highly invasive
      A431 cells were treated with curcumin at various doses .The cytotoxic effects of
      treatment with 5, 10, 15, 20, 25, 30, 35, 40 and 50 umol/L curcumin for 24, 48
      and 72 hours on A431 cells were measured by MTT assay. The invasion capacity of
      cells treated with 5, 10 and 15 umol/L curcumin was measured by Transwell test,
      while adhesive ability was assessed by cell adhesion assay. The effects of 5,10
      and 15 umol/L curcumin on expression levels of STAT3 were determined by Western
      blotting and on transcription levels of STAT3 mRNA by RT-PCR. RESULTS: Treatment
      with curcumin at a doses of more than 15 umol/L for more than 24 hour inhibited
      the growth of A431 cells in a time-and dose-dependent fashion (p<0.001). The
      doses of 15 umol/L and less for 24 hours showed no significant cytotoxic effects
      on the cells, survival rates being more than 85%.The invasion and adhesive
      abilities decreased gradually with the increasing curcumin concentration, 15
      umol/L exerting the strongest inhibitory effects (p<0.05). Curcumin showed
      significant dose-dependent inhibitory effects on the transcription level of STAT3
      mRNA (p<0.05). CONCLUSIONS: Curcumin may reduce the invasive ability of A431
      cells by inhibiting the activation of STAT3 signal pathway and expression of
      STAT3 as a target gene in the pathway.

PMID- 25854368
TI  - Combined expression of metastasis related markers Naa10p, SNCG and PRL-3 and its
      prognostic value in breast cancer patients.
AB  - Combinations of multiple biomarkers representing distinct aspects of metastasis
      may have better prognostic value for breast cancer patients, especially those in
      late stages. In this study, we evaluated the protein levels of N-alpha
      acetyltransferase 10 protein (Naa10p), synuclein-gamma (SNCG), and phosphatase of
      regenerating liver-3 (PRL-3) in 365 patients with breast cancer by
      immunohistochemistry. Distinct prognostic subgroups of breast cancer were
      identified by combination of the three biomarkers. The Naa10p+SNCG-PRL-3-
      subgroup showed best prognosis with a median distant metastasis-free survival
      (DMFS) of 140 months, while the Naa10p-SNCG+PRL-3+ subgroup had the worst
      prognosis with a median DMFS of 60.5 months. Multivariate analysis indicated
      Naa10p, SNCG, PRL-3, and the TNM classification were all independent prognostic
      factors for both DMFS and overall survival (OS). The three biomarker combination
      of Naa10p, SNCG and PRL-3 performed better in patients with lymph node
      metastasis, especially those with more advanced tumors than other subgroups. In
      conclusion, the combined expression profile of Naa10p, SNCG and PRL-3, alone or
      in combination with the TNM classification system, may provide a precise estimate
      of prognosis of breast cancer patients.

PMID- 25854369
TI  - Unpolished Thai rice prevents ACF formation and dysplastic progression in AOM
      induced rats and induces apoptosis through redox alteration in CaCo-2 cells.
AB  - Oxidative stress is associated with colon carcinogenesis including aberrant crypt
      foci (ACF) formation and it plays an important role in pathophysiological changes
      in cancer cells. The aims of this study were to investigate the effects of
      dietary unpolished Thai rice (UTR) on ACF formation and dysplastic progression in
      azoxymethane (AOM)-treated rats. Anti-cancer efficacy of UTR regarding apoptotic
      induction and oxidative redox status in human colon cancer (CaCo-2) cells was
      also investigated. Rats given 20% and 70% of UTR in the diet showed significantly
      and dose-dependently decreased total number of ACF. UTR treatment also was
      strongly associated with the low percentage of dysplastic progression and mucin
      depletion. In addition, we found that UTR significantly induced cancer cell
      apoptosis, increased cellular oxidants, and decreased the level of GSH/GSSG ratio
      in CaCo-2 cells. Our study suggests that UTR supplementation may be a useful
      strategy for CRC prevention with the inhibition of precancerous progression, with
      induction of cancer cell apoptosis through redox alteration. 

PMID- 25854370
TI  - Analyses of multiple factors for determination of "selected patients" who should
      receive rechallenge treatment in metastatic colorectal cancer: a retrospective
      study from Turkey.
AB  - BACKGROUND: Repeating a prior chemotherapy (rechallenge therapy) is an option for
      selected patients with metastatic colorectal cancer, but there is very little
      evidence in the literature for this approach. Thus, we reviewed our registry to
      evaluate prognostic factors and survival of patients who received irinotecan and
      oxaliplatin- based regimens as rechallenge third and fourth-line therapy.
      MATERIALS AND METHODS: Patients who received irinotecan-based or oxaliplatin-base
      regimen as first-line had been rechallenged with third-line or fourth-line
      therapy. These patients were selected from the database of Turkish mCRC registry
      archives between October 2006 and June 2013 and evaluated retrospectively for
      factors effecting progression free survival (PFS) and overall survival (OS) by
      the Kaplan-Meir and Cox-regression methods. RESULTS: Thirty-nine patients were
      enrolled. The median duration of follow-up was 36 months (14-68 months). Thirty
      one patients (76%) died during follow-up. In terms of rechallenge treatments, 29
      patients had received third-line and 10 patients had received fourth-line.
      Response rate (RR) was found to be 12.9%, with stable disease in 19 (48.7%)
      patients. The median PFS was 6 months (95%CI=4.64-7.35 months) and the median OS
      was 11 months (95%CI=8.31-13.7 months). The factors effecting survival (PFS and
      OS) were only being PFS after first-line chemotherapy>=12 months (p=0.007, 95%
      CI=1.75-35.22 and p=0.004, 95%CI=1.44-7.11), both in univariate and multivariate
      analyses. CONCLUSIONS: This study indicates that rechallenge treatment could be a
      good option as a third or later line therapy in patients who had >=12 months PFS
      on receiving first line therapy.

PMID- 25854371
TI  - MDR1 C3435T and C1236T polymorphisms: association with high-risk childhood acute
      lymphoblastic leukemia.
AB  - BACKGROUND: MDR1, one of the most important drug-transporter genes, encodes P-
      glycoprotein (P-gp)-a transporter involved in protecting against xenobiotics and
      multi-drug resistance. The significance of the genetic background in childhood
      acute lymphoblastic leukemia (ALL) is not well understood. MATERIALS AND METHODS:
      To evaluate whether C3435T and C1236T MDR1 polymorphisms are associated with the
      occurrence and outcome of ALL, 208 children with ALL (median age 5.0 yr) and 101
      healthy Thai children were studied by polymerase chain reaction-restriction
      fragment-length polymorphism (PCR-RFLP) assay. RESULTS: C3435T and C1236T MDR1
      polymorphism are significantly associated with the high-risk group (OR=2.6,
      95%CI=1.164-5.808; P=0.028 and OR=2.231, 95%CI=1.068-4.659; p=0.047,
      respectively), indicating that both may be candidates for molecular markers in
      the high-risk group of ALL.

PMID- 25854372
TI  - IL-35 over-expression is associated with genesis of gastric cancer.
AB  - Overexpression of interleukin (IL)-35 has been found in a variety of
      malignancies, but the expression status in gastric cancer has yet to be
      elucidated clearly. In the present study, positive expression of EBI3 and p35 was
      63.3% and 70.0% of cases, respectively. EBI3 expression was strongly related with
      larger tumor size and invasion depth (P<0.05). Similarly, expression of p35 was
      also correlated with larger tumor size (P<0.05). These results indicate that IL
      35 might be involved in growth of gastric cancer. Interestingly, EBI3 and p35
      expressions were positive correlated with Ki-67 expression. Moreover, EBI3
      immunoreactivity was associated with Bcl-2 staining. Our data suggest IL-35 is
      correlated with genesis of gastric cancer by regulating growth and apoptosis.

PMID- 25854373
TI  - Upregulation and clinicopathological significance of long non-coding NEAT1 RNA in
      NSCLC tissues.
AB  - BACKGROUND: Recent reports have shown that nuclear enriched abundant transcript 1
      (NEAT1), a long non- coding RNA (lncRNA), contributes to the precise control of
      gene expression and is related to several human malignancies. However, limited
      data are available on the expression and function of NEAT1 in lung cancer. The
      major objective of the current study was to profile the expression and
      clinicopathological significance of NEAT1 in non-small cell lung cancers
      (NSCLCs). MATERIALS AND METHODS: NEAT1 expression in 125 NSCLC cases and paired
      adjacent non-cancer tissues was assessed by real-time quantitative reverse
      transcription-PCR (qRT-PCR). Relationships between NEAT1 and clinicopathological
      factors were also investigated. RESULTS: The relative level of NEAT1 was 6.98+/
      3.74 in NSCLC tissues, significantly elevated as compared to that of the adjacent
      non-cancer lung tissues (4.83+/-2.98, p<0.001). The area under curve (AUC) of
      high expression of NEAT1 to diagnose NSCLC was 0.684 (95% CI: 0.619~0.750,
      p<0.001). NEAT1 expression was positively correlated with patient age (r=-2.007,
      p=0.047), lymphatic metastasis (r=-2.731, p=0.007), vascular invasion (r=-3.617,
      p=0.001) and clinical TNM stage (r=-4.134, p<0.001). CONCLUSIONS: This study
      indicates that NEAT1 might be associated with oncogenesis and progression in
      NSCLC, and suggests application in molecular targeted therapy.

PMID- 25854374
TI  - Differences in incidence, mortality and survival of breast cancer by regions and
      countries in Asia and contributing factors.
AB  - Although the incidence of breast cancer in Asia remains lower than in North
      America, Western Europe, and Oceania, rates have been increasing rapidly during
      the past few decades, and Asian countries now account for 40% of breast cancer
      cases diagnosed worldwide. Breast cancer mortality has also increased among Asian
      women, in contrast to decreased mortality in Northern America, Western Europe,
      and Oceania. These increased rates are associated with higher prevalence of
      breast cancer risk factors (e.g., reduced parity, delayed childbirth, increased
      obesity) that have accompanied economic development throughout the region.
      However, Asian regions (western, south-central, south-eastern, and eastern) and
      countries differ in the types and magnitude of changes in breast cancer risk
      factors, and cannot be viewed as a single homogeneous group. The objective of
      this paper was to contrast the heterogeneous epidemiology of breast cancer by
      Asian regions and countries, and to suggest potential avenues for future
      research. 

PMID- 25854375
TI  - Histopathological evaluation of urothelial carcinomas in transurethral resection
      urinary bladder tumor specimens: eight years of single center experience.
AB  - BACKGROUND: Urothelial carcinoma (UC) is a malignant neoplasm that most commonly
      occurs in the urinary bladder. The primary aim of this study was to evaluate the
      clinicopathologic features, recurrence and progression in patients with bladder
      urothelial cancer. MATERIALS AND METHODS: The medical records of patients
      diagnosed with UC in the state pathology laboratory between January 2006 and July
      2014 were retrospectively included. Carcinomas were categorized according to age,
      gender, histologic grade, tumor configuration, pathologic staging, recurrence
      status, and progression. RESULTS: A total of 125 (113 men, 12 women) patients
      were examined. The mean age was 65.9 years and the male-to-female urothelial
      cancer incidence ratio was 9.4:1. Low-grade UCs were observed in 85 (68%) and
      high-grade in 40 (32%). A papillary tumor pattern was observed in 67.2% of the
      UCs. Cases were classified with the following pathological grades: 34 (27.2%)
      cases of pTa, 70 (56%) of pT1, and 21 (16.8%) of pT2. Recurrence occurred in 27
      (21.6%) patients. Ten progressed to a higher stage (pT1 to pT2), and three cases
      to higher grade (low to high). We also analyzed the results separately for 70
      (56%) patients 65 years of age and older. CONCLUSIONS: With early detection and
      diagnosis of precursor lesions in older patients, by methods such as standard
      urologic evaluation, urinary cytology, ultrasound scanning and contrast
      urography, and cystoscopy, in addition to coordinated efforts between
      pathologists and urologists, early diagnosis may reduce the morbidity and
      mortality of patients with urothelial carcinoma.

PMID- 25854376
TI  - Adult non Hodgkin's lymphoma patients: experience from a tertiary care cancer
      centre in north east India.
AB  - There is paucity of data on non Hodgkin's lymphoma (NHL) from our population in
      North-East India. In this retrospective study, patients were consecutively
      followed-up to see the clinic-pathological pattern of NHL, various responses, and
      pattern of relapses to first line treatment with chemotherapy. All patients in
      the present study received standard regimen of cyclophosphamde, doxorubicin,
      vincristine, prednisolone (CHOP) with or without rituximab (R-CHOP) as per our
      institutional protocol as first line therapy. Our study has shown that, in our
      adult population, the majority of NHL cases present with stage II and stage III
      disease and extra nodal involvement, B-cell lymphomas and diffuse large cell
      lymphomas being the most common subtypes. International prognostic index was a
      significant factor for varied responses to treatment. The majority of relapses
      after complete remission occurred in the first year. 

PMID- 25854377
TI  - S100A4 expression is closely linked to genesis and progression of glioma by
      regulating proliferation, apoptosis, migration and invasion.
AB  - BACKGROUND: The calcium-binding S100A4 protein is involved in epithelial to
      mesenchymal transition, oncogenic transformation, angiogenesis, cytoskeletal
      integrity, mobility and metastasis of cancer cells. This study aimed to clarify
      the roles of S100A4 in genesis and progression of glioma. MATERIALS AND METHODS:
      S100A4 expression was examined by real-time RT-CPR and Western blot in glioma and
      paired normal brain tissue (n=69), and compared with clinicopathological
      parameters of tumors. In addition, glioma U251 cells transfected with an S100A4
      expressing plasmid were examined for proliferation by MTT, apoptosis by Annexin V
      FITC, and migration and invasion with Transwell chambers. RESULTS: Increased
      S100A4 mRNA expression was found in gliomas, compared with paired non-tumor
      tissue (p<0.001). Gradual elevation of overexpression of S100A4 was observed with
      increasing glioma grade (p<0.001). Astrocytoma showed lower S100A4 mRNA
      expression than oligodendrogliomas, with glioblastomas having highest values
      (p<0.001). Similar results were obtained for S100A4 protein, a positive link
      being found between mRNA and protein expression in gliomas (p<0.001). There was
      higher growth, lower apoptosis, stronger migration and invasion of S100A4
      transfectants than control and mock transfected cells (p<0.001). CONCLUSIONS:
      These findings indicate that up-regulated S100A4 expression is positively linked
      to pathogenesis, progression and histogenesis of glioma by modulating
      proliferation, apoptosis, migration and invasion.

PMID- 25854378
TI  - Morphological factors and cardiac doses in whole breast radiation for left-sided
      breast cancer.
AB  - BACKGROUND: To investigate the impact of the breast size, shape, maximum heart
      depth (MDH), and chest wall hypotenuse (the distance connecting middle point of
      the sternum and the length of lung draw on the selected transverse CT slice) on
      the volumetric dose to heart with whole breast irradiation (WBI) of left-sided
      breast cancer patients. MATERIALS AND METHODS: Fifty-three patients with left
      sided breast cancer undergoing adjuvant intensity-modulated radiotherapy (IMRT)
      were enrolled in the study. The primary breast size and shape, MHD and DCWH
      (chest wall hypotenuse) were contoured on radiotherapy (RT) planning CT slices.
      The dose data of hearts were obtained from the dose-volume histograms (DVHs).
      Data were analyzed by one-way analysis of variance (ANOVA), Student's t-test and
      linear regression analysis. RESULTS: Breast size was independent of heart dose,
      whereas breast shape, MHD and DCWH were correlated with heart dose. The shapes of
      breasts were divided into four types, as the flap type, hemisphere type, cone
      type and pendulous type with heart mean dose being 491.8+/-234.6 cGy, 752.7+/
      219.0 cGy, 620.2+/-275.7 cGy, and 666.1+/-238.0 cGy, respectively. The flap type
      of breasts shows a strong statistically reduction in heart dose, compared to
      others (p=0.008 for V30 of heart). DCWH and MHD were found to be the most
      important parameters correlating with heart dose in WBI. CONCLUSIONS: More
      attention should be paid to the heart dose of non-flap type patients. The MHD was
      found to be the most important parameter to correlate with heart dose in
      tangential WBI, closely followed by the DCWH, which could help radiation
      oncologists and physicsts evaluate heart dose and design RT plan in advance.

PMID- 25854379
TI  - Knowledge, attitudes and practices regarding cervical cancer screening among
      village health volunteers.
AB  - BACKGROUND: In the years 2014, coverage rates of cervical cancer screening in
      Nakornnayok province accounted to 76.5%. This was lower than the government's
      specified goal of 80%. Community health volunteers are members of a Thai
      healthcare alliance established to help promoting healthcare service
      communication and collaboration at the primary level. Such village health
      volunteers (VHVs) are established in most villages. OBJECTIVE: To assess the
      knowledge and attitudes of cervical cancer screening among VHVs. MATERIALS AND
      METHODS: The subjects were 128 VHVs from four Nakornnayok sub-districts; namely
      KlongYai, Chomphol, Buangsan and Suksara, Thailand. The study was conducted from
      December 2014 to January 2015. The questionnaire was designed to assess the
      knowledge and attitude of cervical cancer screening provided by the VHVs. In
      addition, cervical cancer screening coverage rates of each area were collected.
      The demographic data, scores of knowledge, attitudes, practices and the cervical
      cancer screening coverage rates were analyzed by one-way ANOVA. RESULTS: The
      questionnaire reliability was assessed as 0.81. The total knowledge and attitude
      scores were 10 and 15 points. The mean knowledge scores of KlongYai, Chomphol,
      Buangsan and Suksara were 6.8, 7.0, 6.5 and 9.0 points, respectively. The VHVs
      had a high level of overall knowledge about cervical cancer screening. The mean
      attitude scores were 12.4, 13.2, 13.4 and 13.1 points. VHVs had a positive
      attitude to the promotion of cervical cancer screening at the overall level. The
      percentages of VHVs promoting cervical cancer information in respective districts
      were 72.2, 94.3, 94.9 and 50.0. However, the cervical cancer screening coverage
      rates were 62.4%, 34.7%, 80.3% and 47.3% respectively. CONCLUSIONS: The
      knowledge, attitudes and percentages of promoting information of cervical cancer
      screening among VHVs in the four sub-districts were high but did not correlate
      with the cervical screening coverage rates for each area. VHVs needed to
      understand socio-cultural beliefs of the women in the target population and
      design suitable strategies to encourage higher cervical screening coverage.

PMID- 25854380
TI  - Proximity of health care center and cervical cancer screening uptake in Thailand.
AB  - BACKGROUND: Cervical cancer is one of the most common cancers among women
      worldwide, and in Thailand is the second most common cancer among women. In 2008,
      a national cervical cancer screening programme was implemented in Thailand, but
      coverage remains relatively low. OBJECTIVES: The purpose of the study was to
      investigate whether cervical cancer screening uptake is associated with the area
      of residency in Thailand. MATERIALS AND METHODS: A case-control study was carried
      out in women aged 30 to 60 year-old, who live in Sikhiu district, Nakhon
      Ratchasima province, Thailand. Structured-questionnaires were used to interview
      226 women (cases) who had attended cervical cancer screening in the last five
      years and 226 women (controls) who had not. Multiple logistic regression was used
      to investigate the association between the area of residency and cervical cancer
      screening uptake. RESULTS: After controlling for parity, marital status and
      duration of hormonal contraceptive use, an association between the area of
      residence and cervical cancer screening uptake could not demonstrated (ORadj
      1.27, 95%CI: 0.79, 2.04). CONCLUSIONS: We found no evidence to suggest remoteness
      to health care center led to lower cervical cancer screening uptake.

PMID- 25854381
TI  - Treatment outcome for head and neck squamous cell carcinoma in a developing
      country: University Malaya Medical Centre, Malaysia from 2003-2010.
AB  - BACKGROUND: Head and neck cancer (HNC) is the eighth most common cancer as
      estimated from worldwide data. The incidence of HNC in Peninsular Malaysia was
      reported as 8.5 per 100,000 population. This study was aimed to determine the
      treatment outcomes for HNC patients treated in the Oncology Unit of University
      Malaya Medical Centre (UMMC). MATERIALS AND METHODS: All newly diagnosed patients
      with squamous cell carcinoma of head and neck (HNSCC) referred for treatment to
      the Oncology Unit at UMMC from 2003-2010 were retrospectively analyzed. Treatment
      outcomes were 5-year overall survival (OS), cause specific survival (CSS), loco
      regional control (LRC) and radiotherapy (RT) related side effects. Kaplan-Meier
      and log rank analyses were used to determine survival outcomes, stratified
      according to American Joint Committee on Cancer (AJCC) stage. RESULTS: A total of
      130 cases were analysed. Most cases (81.5%) were at late stage (AJCC III-IVB) at
      presentation. The 5-year OS for the whole study population was 34.4% with a
      median follow up of 24 months. The 5-year OS according to AJCC stage was 100%,
      48.2%, 41.4% and 22.0% for stage I, II, III and IVA-B, respectively. The 5-year
      overall CSS and LCR were 45.4% and 55.4%, respectively. Late effects of RT were
      documented in 41.4% of patients. The most common late effect was xerostomia.
      CONCLUSIONS: The treatment outcome of HNSCC at our centre is lagging behind those
      of developed nations. Efforts to increase the number of patients presenting in
      earlier stages, increase in the use of combined modality treatment, especially
      concurrent chemoradiotherapy and implementation of intensity modulated
      radiotherapy, may lead to better outcomes for our HNC patients.

PMID- 25854382
TI  - Preventive and therapeutic effects of quercetin on experimental radiation induced
      lung injury in mice.
AB  - OBJECTIVE: To investigate the protective effect of quercetin on radiation induced
      lung injury (RILI) and related mechanisms. MATERIALS AND METHODS: Mice treated
      with radiation and/or quercetin were sacrificed at 1-8 weeks after irradiation
      under anesthesia. Lung tissues were collected for histological examination.
      Immunohistochemistry (IHC) and Western blotting were performed to detect the
      protein expression of nuclear factor-kappaB (NF-kappaB) and Mitogen-activated
      protein kinases (MAPK) pathway. RESULTS: Hematoxylin and eosin (HE) staining
      showed that radiation controls displayed more severe lung damage than quercetin
      groups, either high or low dose. Results of IHC and Western blotting demonstrated
      the expression level of NF-kappaB to be decreased and that of an inhibitor of NF
      kappaB (Ikappab-alpha) to be increased by the quercetin intervention compared
      with the radiation control group. Numbers of JNK/SAPK, p38 and p44/p42 positive
      inflammatory cells were decreased in the radiation+quercetin injection group
      (P<0.05). CONCLUSIONS: Quercetin may play a radio-protective role in mice lung
      via suppression of NF-kappaB and MAPK pathways.

PMID- 25854383
TI  - Meta-analysis of seven randomized control trials to assess the efficacy and
      toxicity of combining EGFR-TKI with chemotherapy for patients with advanced NSCLC
      who failed first-line treatment.
AB  - BACKGROUND: Some recent clinical trials have been conducted to evaluate a
      combination of EGFR- TKI with chemotherapy for advanced NSCLC patients as second
      line therapy, but the results on the efficacy of such trials are inconsistent.
      The aim of this meta-analysis was to evaluate the efficacy and safety of
      combination of EGFR-TKI and chemotherapy for patients with advanced NSCLC who
      failed first-line treatment. MATERIALS AND METHODS: We searched relative trials
      from PubMed, EMBASE, ASCO Abstracts, ESMO Abstracts, Cochrane Library and
      Clinical Trials.gov. Outcomes analyzed were overall response rate (ORR),
      progression- free survival (PFS), overall survival (OS) and major toxicity.
      RESULTS: Seven trails eventually were included in this meta-analysis, covering
      1,168 patients. The results showed that the combined regimen arm had a
      significant higher ORR (RR 1.76 [1.16, 2.66], p=0.007) and longer PFS (HR 0.75
      [0.66-0.85], p<0.00001), but failed to show effects on OS (HR 0.88 [0.68- 1.15],
      p=0.36). In terms of subgroup results, continuation of EGFR-TKI in addition to
      chemotherapy after first-line EGFR-TKI resistance confered no improvement in ORR
      (RR 0.95 [0.68, 1.33], p=0.75) and PFS (HR 0.89[0.69, 1.15], p=0.38), and OS was
      even shorter (HR1.52 [1.05- 2.21], p=0.03). However, combination therapy with
      EGFR-TKI and chemotherapy after failure of first-line chemotherapy significantly
      improved the ORR (RR 2.06 [1.42, 2.99], p=0.0002), PFS (HR 0.71 [0.61, 0.82],
      p<0.00001) and OS (HR 0.74 [0.62- 0.88], p=0.0008), clinical benefit being
      restricted to combining EGFR-TKI with pemetrexed, but not docetaxel. Grade 3-4
      toxicity was found at significantly higher incidence in the combined regimen arm.
      CONCLUSIONS: Continuation of EGFR-TKI in addition to chemotherapy after first
      line EGFR-TKI resistance should be avoided. Combination therapy of EGFR-TKI and
      pemetrexed for advanced NSCLC should be further investigated for prognostic and
      predictive factors to find the group with the highest benefit of the combination
      strategy.

PMID- 25854384
TI  - Prognostic relevance of human telomerase reverse transcriptase (hTERT) expression
      in patients with gall bladder disease and carcinoma.
AB  - BACKGROUND: Gallbladder carcinoma (GBC) has been stated as an Indian disease,
      with the highest number of cases being reported from certain districts of
      northeast India, which has an ethnically distinct population. Unfortunately there
      are no scientific reports on the underlying molecular mechanisms associated with
      the pathogenesis of the disease from this region. AIM: The present study
      evaluated the role of differential expression of human telomerase reverse
      transcriptase (hTERT) in the development of gall bladder anomalies. MATERIALS AND
      METHODS: Blood and tissue samples were collected from patients undergoing routine
      surgical resection for clinically proven cases of gallbladder disease
      {cholelithiasis (CL, n=50), cholecystitis (CS, n=40) and GBC (n=30) along with
      adjacent histopathologically proved non-neoplastic controls (n=15)} with informed
      consent. Whole blood was also collected from age and sex matched healthy controls
      (n=25) for comparative analysis. Differential hTERT mRNA expression was evaluated
      by semi-quantitative rt-PCR and real-time PCR based analysis using beta-actin as
      an internal control. Evaluation of differential hTERT protein expression was
      studied by Western blot analysis and immunoflourescence. Statistical analysis for
      differential expression and co-relation was performed by SPSSv13.0 software.
      RESULTS: Gallbladder anomalies were mostly prevalent in females. The hTERT mRNA
      and protein expression increased gradiently from normal<CL<CS<GBC cases. Serum
      expression correlated statistically significantly with the tissue based mRNA
      expression pattern of hTERT, with highest expression observed in GBC cases and
      the lowest expression in normal gall bladder. CONCLUSIONS: Higher hTERT
      expression is associated with gallbladder disease susceptibility and severity;
      and may be a useful prognostic marker for gallbladder anomalies.

PMID- 25854385
TI  - G894T and 4a/b polymorphisms of NOS3 gene are not associated with cancer risk: a
      meta-analysis.
AB  - Endothelial nitric oxide synthase (eNOS or NOS3) produces nitric oxide and
      genetic polymorphisms of NOS3 gene play significant roles in various processes of
      carcinogenesis. The results from published studies on the association between
      NOS3 G894T and NOS3 intron 4 (4a/b) polymorphisms and cancer risk are conflicting
      and inconclusive. However, i n order to assess this relationship more precisely,
      a meta-analysis was performed with PubMed (Medline), EMBASE and Google web
      searches until February 2014 to select all published case- control and cohort
      studies. Genotype distribution data were collected to calculate the pooled odd
      ratios (ORs) and 95% confidence intervals (CIs) to evaluate the strength of
      association. A total of 10,546 cancer cases and 10,550 controls were included
      from twenty four case-control studies for the NOS3 G894T polymorphism. The
      results indicated no significant association with cancer risk as observed in
      allelic (T vs G: OR=1.024, 95%CI=0.954 to 1.099, p=0.508), homozygous (TT vs GG:
      OR=1.137, 95%CI=0.944 to 1.370, p=0.176), heterozygous (GT vs GG: OR=0.993,
      95%CI=0.932 to 1.059, p=0.835), recessive (TT vs GG+GT: OR=1.100, 95%CI=0.936 to
      1.293, p=0.249) and dominant (TT+GT vs GG: OR=1.012, 95%CI=0.927 to 1.105,
      p=0.789) genetic models. Similarly, a total of 3,449 cancer cases and 3,691
      controls were recruited from fourteen case-control studies for NOS3 4a/b
      polymorphism. Pooled results indicated no significant association under allelic
      (A vs B: OR=0.981, 95%CI=0.725 to 1.329, p=0.902), homozygous (AA vs BB:
      OR=1.166, 95%CI=0.524 to 2.593, p=0.707), heterozygous (BA vs BB: OR=1.129,
      95%CI=0.896 to 1.422, p=0.305), dominant (AA+BA vs BB: OR=1.046, 95%CI=0.779 to
      1.405, p=0.763) and recessive (AA vs BB+BA: OR=1.196, 95%CI=0.587 to 2.439,
      p=0.622) genetic contrast models. This meta-analysis suggests that G894T and 4a/b
      polymorphisms of NOS3 gene are not associated with increased or decreased risk of
      overall cancer. 

PMID- 25854386
TI  - Aloe vera inhibits proliferation of human breast and cervical cancer cells and
      acts synergistically with cisplatin.
AB  - Many of the anti-cancer agents currently used have an origin in natural sources
      including plants. Aloe vera is one such plant being studied extensively for its
      diverse health benefits, including cancer prevention. In this study, the
      cytotoxic potential of Aloe vera crude extract (ACE) alone or in combination with
      cisplatin in human breast (MCF-7) and cervical (HeLa) cancer cells was studied by
      cell viability assay, nuclear morphological examination and cell cycle analysis.
      Effects were correlated with modulation of expression of genes involved in cell
      cycle regulation, apoptosis and drug metabolism by RT-PCR. Exposure of cells to
      ACE resulted in considerable loss of cell viability in a dose- and time-dependent
      fashion, which was found to be mediated by through the apoptotic pathway as
      evidenced by changes in the nuclear morphology and the distribution of cells in
      the different phases of the cell cycle. Interestingly, ACE did not have any
      significant cytotoxicity towards normal cells, thus placing it in the category of
      safe chemopreventive agent. Further, the effects were correlated with the
      downregulation of cyclin D1, CYP 1A1, CYP 1A2 and increased expression of bax and
      p21 in MCF-7 and HeLa cells. In addition, low dose combination of ACE and
      cisplatin showed a combination index less than 1, indicating synergistic growth
      inhibition compared to the agents applied individually. In conclusion, these
      results signify that Aloe vera may be an effective anti-neoplastic agent to
      inhibit cancer cell growth and increase the therapeutic efficacy of conventional
      drugs like cispolatin. Thus promoting the development of plant-derived
      therapeutic agents appears warranted for novel cancer treatment strategies. 

PMID- 25854387
TI  - The BRAFT1799A mutation is not associated with occult contralateral carcinoma in
      patients with unilateral papillary thyroid microcarcinoma.
AB  - BACKGROUND: The phenomenon of occult carcinoma maybe observed in patients with
      clinically unilateral papillary thyroid microcarcinoma (PTMC). Although many
      studies have reported that the BRAFT1799A mutation is associated with aggressive
      PTMC, the relationship between BRAFT1799A mutation and occult carcinoma is
      unclear. The aim of this study was to investigate the risk factors, including
      BRAFT1799A mutation, for occult contralateral carcinoma in clinically unilateral
      PTMC accompanied by benign nodules in the contralateral lobe. MATERIALS AND
      METHODS: From January 2011 to December 2013,we prospectively enrolled 89
      consecutive PTMC patients with clinically unilateral carcinoma accompanied by
      benign nodules in the contralateral lobe who received a total thyroidectomy and
      cervical lymph node dissection. BRAFT1799A mutation was tested by pyrosequencing
      on postoperative paraffin specimens. The frequency and predictive factors for
      occult contralateral carcinoma were analyzed with respect to the following
      variables: age, gender, family history, tumor size, presence of Hashimoto
      thyroiditis, extrathyroidal extension, central lymph node metastasis,
      multifocality of primary tumor, or BRAFT1799A mutation. RESULTS: A total of 36
      patients (40.4%) had occult PTMC in the contralateral lobe. The median diameter
      of the occult tumors was 0.33+/-0.21 cm. The BRAFT1799A mutation was found in 38
      cases (42.7%). According to the univariate analysis, there were no significant
      differences between the presence of occult contralateral carcinoma and age,
      gender, family history, tumor size, presence of Hashimoto thyroiditis,
      extrathyroidal extension, central lymph node metastasis, multifocality of primary
      tumor, or BRAFT1799A mutation. CONCLUSIONS: Using current methods, it is
      difficult to preoperatively identify patients with PTMC, and further research is
      needed to determine predictive factors for the presence of occult contralateral
      carcinoma in patients with unilateral PTMC.

PMID- 25854388
TI  - Hypoxia induced high expression of thioredoxin interacting protein (TXNIP) in non
      small cell lung cancer and its prognostic effect.
AB  - Although associations between thioredoxin interacting protein (TXNIP) and cancers
      have been recognized, the effects of TXNIP on non-small cell lung cancer (NSCLC)
      prognosis remained to be determined in detail. In addition, while hypoxia is a
      key characteristic of tumor cell growth microenvironment, the effect of hypoxia
      on TXNIP expression is controversial. In this study, formaldehyde fixed and
      paraffin embedded (FFPE) samples of 70 NSCLC patients who underwent resection
      between January 2010 and December 2011 were obtained. Evaluation of TXNIP and
      hypoxia inducible factor-1alpha (HIF-1alpha) protein expression in FFPE samples
      was made by immunohistochemistry. By Kaplan-Meier method, patients with high
      TXNIP expression demonstrated a significantly shorter progression free survival
      (PFS) compared with those with low TXNIP expression (18.0 months, 95%CI: 11.7,
      24.3 versus 23.0 months, 95%CI: 17.6, 28.4, P=0.02). High TXNIP expression level
      was also identified as an independent prognostic factor by Cox regression
      analysis (adjusted hazard ratio: 2.46; 95%CI: 1.08, 5.56; P=0.03). Furthermore,
      TXNIP expression was found to be significantly correlated with HIF- 1alpha
      expression (Spearman correlation=0.67, P=0.000). To further confirm correlations,
      we established a tumor cell hypoxic culture model. Expression of TXNIP was up
      regulated in all three NSCLC cell lines (A549, SPC-A1, and H1299) under hypoxic
      conditions. This study suggests that hypoxia induces increased TXNIP expression
      in NSCLC and high TXNIP expression could be a poor prognostic marker. 

PMID- 25854389
TI  - Reproductive risk factors differ among breast cancer patients and controls in a
      public hospital of Paraiba, northeast Brazil.
AB  - The incidence and mortality rates of breast cancer in Northeast Brazil are
      increasing and little is known about prevailing reproductive factors contributing
      to this increase. A case-control study was conducted in a public hospital of
      Campina Grande, state of Paraiba, including 81 women with diagnosed invasive
      breast cancer and 162 age matched (+/-5 years) controls. Binominal logistic
      regression analysis was applied to estimate odds ratio (OR) and confidence
      intervals (CI) of risk factors. In this model, age at menarche<=12 (OR=2.120; CI:
      1.043-4.308; p=0.038), single parity (OR=3.748; CI: 1.459- 9.627; p=0.06) and
      reproductive period>10 years (OR=3.042; CI: 1.421- 6.512; p=0.04) were identified
      as independent variables that significantly increased breast cancer risk of
      parous women. Compared to parous women who never practised breastfeeding, total
      breastfeeding time>24 months decreased the risk of breast cancer (OR=0.258; CI:
      0.084- 0.787; p=0.017). The results indicated that modifiable reproductive
      factors contribute to breast cancer risk in women included in the present study.
      Women's knowledge about factors such as the protective effect of breastfeeding
      could reduce the risk of breast cancer.

PMID- 25854390
TI  - A new tool to predict survival after radiosurgery alone for newly diagnosed
      cerebral metastases.
AB  - Many patients with few cerebral metastases receive radiosurgery alone. The goal
      of this study was to create a tool to estimate the survival of such patients. To
      identify characteristics associated with survival, nine variables including
      radiosurgery dose, age, gender, Eastern cooperative oncology group performance
      score (ECOG-PS), primary tumor type, number/size of cerebral metastases, location
      of cerebral metastases, extra-cerebral metastases and time between cancer
      diagnosis and radiosurgery were analyzed in 214 patients. On multivariate
      analysis, age (p=0.03), ECOG-PS (p=0.02) and extra-cerebral metastases (p<0.01)
      had significant impacts on survival. Scoring points for each patient were
      obtained from 12-month survival rates (in %) related to the significant variables
      divided by 10. Addition of the scoring points of the three variables resulted in
      a patient's total predictive score. Two groups were designed, A (10-14 points)
      and B (16-17 points). Twelve-month survival rates were 33% and 77%, respectively
      (p<0.001). Median survival times were 8 and 20 months, respectively. Because most
      patients of group A died from extra-cerebral disease and/or new cerebral lesions,
      early systemic treatment and additional WBI should be considered. As cause of
      death in group B was mostly new cerebral metastases, additional WBI appears even
      more important for this group. 

PMID- 25854391
TI  - Lack of influence of TP53 Arg72Pro and 16bp duplication polymorphisms on risk of
      breast cancer in Iran.
AB  - TP53 is assumed to be a very important tumour suppressor gene, as illustrated by
      recent reports that have shown effects of its polymorphisms on breast cancer
      risk. Arg72Pro and PIN3(16bp duplication) polymorphisms are proposed to have an
      effective role in structural changes of p53 and have therefore attracted interest
      as a risk factor for breast cancer in different populations. The aim of this
      study was to examine and determine whether p53 codon 72 and PIN3 Ins16 bp may be
      associated with an increased risk for breast cancer in female patients from the
      northwest of Iran. Genotyping was performed by PCR-RFLP (polymerase chain
      reaction-restriction fragment length polymorphism) method for a total of 100
      women with breast cancer and 100 healthy women without any background of cancer,
      focusing on the TP53 Arg72Pro-16Del/Ins haplotypes and the combined genotypes.
      The results in this study established no statistical significant distinctions
      between the genotypes and allele frequency were found for Arg72Pro and PIN3 Ins
      16 bp polymorphisms between patients and controls. 

PMID- 25854392
TI  - Regulatory effects of WRAP53 on radiosensitivity of laryngeal squamous cell
      carcinoma cells.
AB  - BACKGROUND: Telomere length is closely associated with cellular radiosensitivity
      and WRAP53 is required for telomere addition by telomerase. In this research we
      assessed radiosensitivity of laryngeal squamous cell carcinoma Hep-2 cell lines
      after WRAP53 inhibition, and analyzed the molecular mechanisms. MATERIALS AND
      METHODS: phWRAP53-siRNA and pNeg-siRNA were constructed and transfected into Hep
      2 cells with lipofectamine. Expression of WRAP53 was analyzed by RT-PCR and
      Western-blottin, radiosensitivity of Hep-2 cells was assessed colony formation
      assay, and the relative length of telomeres was measured by QPCR. RESULTS: The
      data revealed that the plasmid of phWRAP53-siRNA was constructed successfully,
      and the mRNA and protein levels of WRAP53 were both obviously reduced in the Hep
      2 cell line transfected with phWRAP53-siRNA. After Hep-2 cells were irradiated
      with X-rays, the D0 and SF2 were 2.481 and 0.472, respectively, in the phWRAP53
      siRNA group, much lower than in the control group (D0 and SF2 of 3.213 and 0.592)
      (P<0.01). The relative telomere length in the phWRAP53-siRNA group was 0.185+/
      0.01, much lower than in the untreated group (0.523+/-0.06) and the control group
      (0.435+/-0.01). CONCLUSIONS: Decreasing the expression of WRAP53 using RNA
      interference technique can enhance the radiosensitivity of Hep-2 cell lines by
      influencing the telomere length. WRAP53 is expected to be a new target to
      regulate the radiosensitization of tumor cells.

PMID- 25854393
TI  - Serum carotenoid, retinol and tocopherol concentrations and risk of cervical
      cancer among Chinese women.
AB  - BACKGROUND: Despite many epidemiological studies on the effects of dietary
      antioxidant micronutrients on risk of cervical cancer, the findings remain
      uncertain and little evidence is available for serum nutrient markers. The
      present study aimed to examine the relationship between serum carotenoid, retinol
      and tocopherol concentrations and risk of cervical cancer among Chinese women.
      MATERIALS AND METHODS: We conducted a hospital-based case- control study in which
      358 adults (158 incident cases and 200 controls) were recruited from Xinjiang,
      China. Serum levels of carotenoids (alpha-carotene, beta-carotene, beta
      cryptoxanthin, lycopene and lutein/zeaxanthin), retinol, and tocopherols (alpha
      tocopherol and gamma-tocopherol) were assessed by reverse-phase high-performance
      liquid chromatography. RESULTS: We found inverse associations between serum
      carotenoid (alpha-carotene, beta-carotene, and lutein/zeaxanthin) and tocopherol
      (alpha-tocopherol) concentrations and the risk of cervical cancer after adjusting
      for potential confounders, but a null association for retinol. The ORs for 1-SD
      increase were 0.71 (95% CI: 0.56- 0.92; p=0.003) for total carotenoids and 0.75
      (95% CI: 0.60-0.94; p=0.008) for total tocopherols. CONCLUSIONS: These results
      show that higher serum concentrations of some carotenoids and tocopherols are
      associated with a lower risk of cervical cancer among Chinese women.

PMID- 25854394
TI  - Thyroid transcription factor-1 expression in advanced non- small cell lung
      cancer: impact on survival outcome.
AB  - BACKGROUND: The prognostic role of thyroid transcription factor-1 (TTF-1)
      expression in lung cancer has been assessed but with inconsistent results. The
      present study aimed to evaluate the prognostic value of TTF1 expression in
      advanced non-squamous non-small cell lung cancer (NSCLC). MATERIALS AND METHODS:
      In this retrospective study, patients with stage IIIB-IV non-squamous NSCLC were
      enrolled. Progression free survival (PFS) and overall survival (OS) were assessed
      according to TTF1 expression status, age categories (<=60 vs >60 years), gender,
      performance status (PS) (0-2 vs 3-4), type of 1st line chemotherapy (pemetrexed
      containing vs others) and EGFR status. RESULTS: A total of 120 patients were
      included. In univariate analysis, PFS was improved in patients with PS 0-2 (7.0
      vs 2.0 months, p=0.002) and those who received pemetrexed-containing chemotherapy
      (9.2 vs 5.8 months, p=0.004). OS was improved in female patients (23.0 vs 8.7
      months, p<0.0001), PS 0-2 (14.4 vs 2.0 months, p<0.0001), those with pemetrexed
      containing chemotherapy (17.0 vs 11.0 months, p=0.019), TTF1-positive (12.8 vs
      5.8 months, p=0.011) and EGFR- mutant patients (23.0 vs 11.7 months, p=0.006). In
      multivariate analysis, male gender (HR=2.34, p=0.025) and non-pemetrexed
      containing therapy (HR=2.24, p=0.022) were independent predictors of worse PFS.
      Wild EGFR status (HR=2.49, p=0.015) and male gender (HR=2.78, p=0.008) were
      predictors of worse OS. CONCLUSIONS: Pemetrexed-containing therapy significantly
      improved PFS while OS was improved in EGFR mutant patients. Female patients had
      better PFS and OS. TTF1 expression was not a prognostic marker in advanced non
      squamous NSCLC.

PMID- 25854395
TI  - Can induction chemotherapy before concurrent chemoradiation impact
      circumferential resection margin positivity and survival in low rectal cancers?
AB  - BACKGROUND: Distance from anal verge and abdominoperineal resection are risk
      factors for circumferential resection margin (CRM) positivity in rectal cancer.
      Induction chemotherapy (IC) before concurrent chemoradiation (CRT) has emerged as
      a new treatment modification. Impact of IC before concurrent CRT on CRM
      positivity in low rectal cancer remains to be independently studied. The
      objective of this study was to determine CRM positivity in low rectal cancer,
      with and without prior IC, and to identify predictors of disease free and overall
      survival. MATERIALS AND METHODS: Patients who underwent surgery for rectal cancer
      between 2005 and 2011 were retrospectively reviewed and divided into two groups.
      Group 1 received IC before CRT and Group 2 did not. Demographics,
      clinicopathological variables and CRM status were compared. Actuarial 5 year
      disease free survival (DFS), overall survival (OS) and independent predictors of
      survival were determined. RESULTS: Patients in the IC group presented with
      advanced stage (Stage 3=89.2% versus 75.4%) (P=0.02) but a high rate of total
      mesorectal excision (TME) (100% versus 93.4%) (P=0.01) and sphincter preservation
      surgery (54.9 % versus 22.9%) (P=0.001). Patients with low rectal cancer who
      received IC had a significantly low positive CRM rate (9.2% versus 34%)
      (P=0.002). Actuarial 5 year DFS in IC and no IC groups were 39% and 43% (P=0.9)
      and 5 year OS were 70% and 47% (P=0.003). Pathological tumor size [HR: 2.2, CI:
      1.1-4.5, P=0.01] and nodal involvement [HR: 2, CI: 1.08-4, P=0.02] were
      independent predictors of relapse while pathological nodal involvement [HR: 2.6,
      CI: 1.3-4.9, P=0.003] and IC [HR: 0.7, CI: 0.5-0.9, P=0.02] were independent
      predictors of death. CONCLUSIONS: In low rectal cancer, induction chemotherapy
      before CRT may significantly decrease CRM positivity and improve 5 year overall
      survival.

PMID- 25854396
TI  - Upper gastrointestinal tract polyps: what do we know about them?
AB  - BACKGROUND: This study aimed to evaluate upper gastrointestinal polyps detected
      during esophago- gastroduodenoscopy tests. MATERIALS AND METHODS: We conducted a
      retrospective analysis on data regarding 55,987 upper gastrointestinal endoscopy
      tests performed at the endoscopy unit of Istanbul Education and Research Hospital
      between January 2006 and June 2012. RESULTS: A total of 66 upper gastrointestinal
      polyps from 59 patients were analyzed. The most common clinical symptom was
      dyspepsia, observed in 41 cases (69.5%). The localizations of the polyps were as
      follows: 29 in the antrum (43.9%), 15 in the corpus (22.7%), 11 in the cardia
      (16.7%), 3 in the fundus (4.54%), 3 in the second portion of the duodenum
      (4.54%), 2 in the bulbus (3.03%) and 3 in the lower end of the esophagus (4.54%).
      Histopathological types of polyps included hyperplastic polyps (44) (66.7%),
      faveolar hyperplasia (8) (12.1%), fundic gland polyps (4) (6.06%), squamous cell
      polyps (4) (6.06%), hamartomatous polyps (3) (4.54%), and pyloric gland adenoma
      (3) (4.54%). Histopathological analysis of the gastric mucosa showed chronic
      atrophic gastritis in 30 cases (50.84%), HP infection in 33 cases (55.9%) and
      intestinal metaplasia in 19 cases (32.20%). In 3 cases with multiple polyps,
      adenocarcinoma was detected in hyperplastic polyps. CONCLUSIONS: Among polypoid
      lesions of the upper gastrointestinal tract, the most common histological type is
      hyperplastic polyps. Generally, HP infection is associated with chronic atrophic
      gastritis and intestinal metaplasia. The incidence of adenocarcinoma tends to be
      higher in patients with multiple hyperplastic polyps.

PMID- 25854397
TI  - Application of multiplex nested methylated specific PCR in early diagnosis of
      epithelial ovarian cancer.
AB  - OBJECTIVE: To explore the application of multiplex nested methylated specific
      polymerase chain reaction (PCR) in the early diagnosis of epithelial ovarian
      carcinoma (EOC). MATERIALS AND METHODS: Serum and fresh tissue samples were
      collected from 114 EOC patients. RUNX3, TFPI2 and OPCML served as target genes.
      Methylation levels of tissues were assessed by multiplex nested methylated
      specific PCR, the results being compared with those for carcinoma antigen 125
      (CA125). RESULTS: The serum free deoxyribose nucleic acid (DNA) methylation
      spectrum of EOC patients was completely contained in the DNA spectrum of cancer
      tissues, providing an accurate reflection of tumor DNA methylation conditions.
      Serum levels of CA125 and free DNA methylation in the EOC group were evidently
      higher than those in benign lesion and control groups (p<0.05). Patients with
      early EOC had markedly lower serum CA125 than those with advanced EOC (p<0.05),
      but there was no significant difference in free DNA methylation (p>0.05). The
      sensitivity, specificity and positive predicative value (PPV) of multiplex nested
      methylated specific PCR were significantly higher for detection of all patients
      and those with early EOC than those for CA125 (p<0.05). In the detection of
      patients with advanced EOC, the PPV of CA125 detection was obviously lower than
      that of multiplex nested methylated specific PCR (p>0.05), but there was no
      significant difference in sensitivity (p>0.05). CONCLUSIONS: Serum free DNA
      methylation can be used as a biological marker for EOC and multiplex nested
      methylated specific PCR should be considered for early diagnosis since it can
      accurately determine tumor methylation conditions.

PMID- 25854398
TI  - Association between the epidermal growth factor 61*A/G polymorphism and
      hepatocellular carcinoma risk: a meta-analysis.
AB  - The epidermal growth factor (EGF) may play a pathological role in hepatocellular
      carcinoma (HCC). However, the conclusions of published reports on the
      relationship between the EGF 61*A/G polymorphism and HCC risk remain
      controversial. To derive a more precise estimation we performed a meta-analysis
      based on 14 studies that together included 2,506 cases and 4,386 controls.
      PubMed, EMBASE, Web of Knowledge and the Chinese National Knowledge
      Infrastructure (CNKI) databases were used to retrieve articles up to August 1,
      2014. The crude odds ratios (ORs) with 95% confidence intervals (95%CIs) were
      calculated to evaluate the association. Meta-analysis results showed a
      significant association between the EGF 61*A/G polymorphism and HCC risk in all
      four genetic models (allele model: OR=1.25, 95%CI=1.12-1.40; dominant model:
      OR=1.32, 95%CI=1.14-1.54; recessive model: OR=1.33, 95%CI=1.12-1.58; homozygous
      model: OR=1.59, 95%CI=1.33- 1.90). Moreover, significant associations were
      observed when stratified by ethnicity, source of controls, etiology and genotype
      methods. Thus, this meta-analysis suggests that the G-allele of the EGF 61*A/G
      polymorphism is associated with an increased risk of HCC, especially in Asians
      and Caucasians, without influence from the source of controls or etiological
      diversity. Further studies with larger population sizes are needed to confirm
      these results.

PMID- 25854399
TI  - Factors affecting prognosis in metastatic colorectal cancer patients.
AB  - BACKGROUND: Colorectal cancer (CRC) is a major cause of mortality in developed
      countries, and it is the third most frequent malignancy in Turkey. There are many
      biological, genetic, molecular, and tissue-derived prognostic factors for CRCs.
      In this study, we evaluated prognostic factors in patients who were metastatic at
      diagnosis or progressed to metastatic disease during follow-up. PATIENTS AND
      METHODS: This study included 116 patients with malignancies either in the colon
      or rectum. Of these, 65 had metastatic disease at diagnosis, and 51 progressed to
      metastatic disease during the course of the disease. The parameters evaluated
      were age, gender, comorbidity, performance status and stage of the disease at the
      beginning, localization, history of surgery, chemotherapy regimen, response to
      first-line treatment, K-RAS status, site and number of metastases, expression of
      tumor predictors (CEA, CA19-9), and survival times. A multivariate analysis
      conducted with factors that considered statistically significant in the
      univariate analysis. FINDINGS: Median age was 56 (32-82) years and the male/
      female ratio was 80/36. Eleven patients were at stage II, 40 at stage III, and 65
      at stage IV at diagnosis. Twenty three patients had tumor in the right colon, 48
      in the left colon, and 45 in the rectum. Ninety seven patients were operated, and
      27 had surgical metastasectomy. Ninety three patients received targeted therapy.
      At the end of follow-up, 61 patients had died, and 55 survived. Metastatic period
      survival times were longer in the adjuvant group, but the difference did not
      reach the level of statistical significance (adjuvant group: median 29 months,
      metastatic group: median 22 months; p=0.285). In the adjuvant group before the
      metastatic first-line therapy, CEA and CA 19-9 levels were significiantly lower
      compared to the metastatic group (p<0.005). We also found that patients with
      elevated tumor predictor (CEA, CA 19-9) levels before the first-line therapy had
      significiantly poorer prognosis and shorter survival time. Survival was
      significiantly better with the patients who were younger than 65 years of age,
      had better initial performance status, a history of primary surgery and
      metastatectomy, and single site of metastasis. Those who benefitted from the
      first-line therapy were K-RAS wild type and whose tumor markers (CEA, CA 19-9)
      were not elevated before the first line therapy. CONCLUSIONS: Among the patients
      with metastatic CRC, those who benefited from first-line therapy, had history of
      metastasectomy, were K-RAS wild type and had low CA 19-9 levels before the first
      line therapy, showed better prognosis independent of other factors.

PMID- 25854400
TI  - Effects of EGFR, CK19, CK20 and Survinin gene expression on radiotherapy results
      in patients with locally advanced head and neck cancer.
AB  - PURPOSE: To investigate the effects of epidermal growth factor receptor (EGFR),
      cytokeratin 19 (CK19), cytokeratin 20 (CK20) and survinin gene expression on
      local control (LC) and overall survival (OS) in patients with locally advanced
      head and neck cancer (LAHNC) who were administered radiotherapy (RT). MATERIALS
      AND METHODS: Twenty-six patients who were admitted to Uludag University Medical
      Faculty Department of Radiation Oncology with a diagnosis of LAHNC (GIII-GIV)
      were included in this study. Gene expression was evaluated in tumor tissues and
      peripheral blood. RNA isolation was performed on paraffinized tumor tissues and
      peripheral blood samples obtained before RT (BR). The densities of the obtained
      RNAs were analyzed at 260/280 nm. cDNA samples obtained from total RNA,EGFR,
      CK19, CK20 and survinin gene expression levels were assessed via the Sybr Green
      method and data were analyzed with the DeltaDeltaCt method. The same process was
      repeated for peripheral blood samples taken after RT (AR). RESULTS: The
      female/male ratio was 3:23 and the mean age was 56.5 years (38-75 years). After
      radiotherapy, CK19 and CK20 levels in the peripheral blood were found to be
      correlated according to Pearson correlation analysis(p=0.049). This result
      indicates a possibility of remaining positive for CK19 and CK20 in the peripheral
      blood even after RT in patients with CK19, CK20, and EGFR positive tumors before
      RT. There was a statistically significant correlation between survinin levels
      measured BR and AR (p=0.028). CONCLUSIONS: In this study, we found that patients
      with any EGFR, CK19, CK20 or survinin positivity in their peripheral blood obtain
      less benefit from radiotherapy. A wider patient population and advanced protein
      analyses are necessary in order to increase the reliability of our findings.

PMID- 25854401
TI  - Influence of maternal environmental tobacco smoke exposure assessed by hair
      nicotine levels on birth weight.
AB  - BACKGROUND: While the perinatal outcomes of active maternal smoking are well
      documented, results of the effects of environmental tobacco smoke (ETS) exposure
      during pregnancy are inconsistent. We aimed to examine the effect of ETS
      exposure, assessed by maternal hair nicotine levels at 35th week of gestation, on
      birth weight and the risk of small for gestational age (SGA) and low birth weight
      (LBW). MATERIALS AND METHODS: A total of 871 non-smoking healthy pregnant women
      were recruited by one Korean hospital between 1 October 2006 and 31 July 2007.
      Hair samples were collected and anthropometric questionnaires administered at
      35th week of gestation. The primary outcome was birth weight and secondary
      outcomes were the risk of babies being SGA and LBW. RESULTS: Log-transformed hair
      nicotine concentrations were inversely related with birth weight after adjusting
      for confounding variables (beta=-0.077, p=0.037). After stratifying hair nicotine
      levels by tertiles (T1, low [0.0-0.28 ng/mg]; T2, medium [0.29-0.62 ng/mg]; and
      T3, high [0.63-5.99 ng/mg]), the mean birth weight in each groups were 3,342 g
      (T1) 3,296 g (T2) and 3,290 g (T3), respectively. However the difference between
      groups was not statistically significant by analysis of co-variance (ANCOVA)
      adjusting for covariates (p=0.062). In logistic regression analysis, the risk of
      SGA was higher in the T3 (OR=1.59, 95%CI 1.05-2.42) than in the reference group
      (T1), after controlling for confounding variables. The risk of low birth weight
      (<2,500 g, LBW) was not significantly higher (OR=1.44, 95%CI 0.95-2.19), but the
      risk of babies being below 3,000g birth weight was increased in the T3 group
      (OR=1.53, 95%CI 1.00-2.36) compared with that in the T1 group. CONCLUSIONS:
      Maternal ETS exposure during pregnancy was inversely related with birth weight.
      The risk of SGA increased in the highest ETS exposure group compared with in the
      low exposure group. To prevent ETS exposure during pregnancy, more comprehensive
      tobacco control policies are needed.

PMID- 25854402
TI  - Anti-proliferation effects of isorhamnetin on lung cancer cells in vitro and in
      vivo.
AB  - BACKGROUND: Isorhamnetin (Iso), a novel and essential monomer derived from total
      flavones of Hippophae rhamnoides that has long been used as a traditional Chinese
      medicine for angina pectoris and acute myocardial infarction, has also shown a
      spectrum of antitumor activity. However, little is known about the mechanisms of
      action Iso on cancer cells. OBJECTIVES: To investigate the effects of Iso on A549
      lung cancer cells and underlying mechanisms. MATERIALS AND METHODS: A549 cells
      were treated with 10~320 MUg/ml Iso. Their morphological and cellular
      characteristics were assessed by light and electronic microscopy. Growth
      inhibition was analyzed by MTT, clonogenic and growth curve assays. Apoptotic
      characteristics of cells were determined by flow cytometry (FCM), DNA
      fragmentation, single cell gel electrophoresis (comet) assay, immunocytochemistry
      and terminal deoxynucleotidyl transferase nick end labeling (TUNEL) . Tumor
      models were setup by transplanting Lewis lung carcinoma cells into C57BL/6 mice,
      and the weights and sizes of tumors were measured. RESULTS: Iso markedly
      inhibited the growth of A549 cells with induction of apoptotic changes. Iso at 20
      MUg/ml, could induce A549 cell apoptosis, up-regulate the expression of apoptosis
      genes Bax, Caspase-3 and P53, and down-regulate the expression of Bcl-2, cyclinD1
      and PCNA protein. The tumors in tumor-bearing mice treated with Iso were
      significantly smaller than in the control group. The results of apoptosis-related
      genes, PCNA, cyclinD1 and other protein expression levels of transplanted Lewis
      cells were the same as those of A549 cells in vitro. CONCLUSIONS: Iso, a natural
      single compound isolated from total flavones, has antiproliferative activity
      against lung cancer in vitro and in vivo. Its mechanisms of action may involve
      apoptosis of cells induced by down-regulation of oncogenes and up-regulation of
      apoptotic genes.

PMID- 25854403
TI  - Quantitative changes in tumor-associated M2 macrophages characterize
      cholangiocarcinoma and their association with metastasis.
AB  - The tumor microenvironment (TME) includes numerous non-neoplastic cells such as
      leukocytes and fibroblasts that surround the neoplasm and influence its growth.
      Tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs) are
      documented as key players in facilitating cancer appearance and progression.
      Alteration of the macrophage (CD68, CD163) and fibroblast (alpha-SMA, FSP-1)
      cells in Opisthorchis viverrini (Ov)-induced cholangiocarcinoma (CCA) was here
      assessed using liver tissues from an established hamster model and from 43 human
      cases using immunohistochemistry. We further investigated whether M2-activated
      TAMs influence CCA cell migration ability by wound healing assay and Western blot
      analysis. Macrophages and fibroblasts change their phenotypes to M2-TAMs (CD68+,
      CD163+) and CAFs (alpha-SMA+, FSP-1+), respectively in the early stages of
      carcinogenesis. Interestingly, a high density of the M2-TAMs CCA in patients is
      significantly associated with the presence of extrahepatic metastases (p=0.021).
      Similarly, CD163+ CCA cells are correlated with metastases (p=0.002), and they
      may be representative of an epithelial-to-mesenchymal transition (EMT) with
      increased metastatic activity. We further showed that M2-TAM conditioned medium
      can induce CCA cell migration as well as increase N-cadherin expression
      (mesenchymal marker). The present work revealed that significant TME changes
      occur at an early stage of Ov-induced carcinogenesis and that M2-TAMs are key
      factors contributing to CCA metastasis, possibly via EMT processes.

PMID- 25854404
TI  - What do Web users know about skin self-examination and melanoma symptoms?
AB  - BACKGROUND: Skin self-examination (SSE) may facilitate early diagnosis of
      melanoma at a potentially curable stage. Little data are available concerning the
      SSE frequency and knowledge about the symptoms of melanoma in non-patient
      populations. The aim of our study was to assess the performance of skin self
      examination, recognition of potential melanoma symptoms as well as behavior
      related to sun exposure among web users in Poland. MATERIALS AND METHODS: A cross
      sectional study was conducted among readers of a scientific portal. Invited
      respondents were asked to complete an online questionnaire. Finally, statistical
      analysis was conducted on 4,919 surveys towards potential clinical signs of
      melanoma and SSE performance. RESULTS: Approximately 60% of respondents had ever
      performed SSE in their life. Only 18.4% declared performance on a regular,
      monthly, basis. Factors promoting this activity were established to be bigger
      place of residence, higher education and sensitive skin phototype, higher level
      of knowledge concerning melanoma, safe tanning rules and, especially, past
      surgical excision of naevi. Declared longer use of tanning beds was linked to
      understanding better the importance of clinical features of melanoma. Awareness
      of hazardous behavior during sunbathing is associated with the attempts to change
      them. CONCLUSIONS: Regular SSE is not a common practice, whilst the knowledge
      about the clinical features of melanoma is varied. Therefore, constant pressure
      should be put on promotion of regular skin self-examination and teaching its
      proper techniques, including familiarity with the ABCD (asymmetry; border; color;
      diameter) rule and its extension of "EFG" (elevated, firm, progressive growth)
      criteria.

PMID- 25854405
TI  - Importance of the cell block technique in diagnosing patients with non-small cell
      carcinoma accompanied by pleural effusion.
AB  - BACKGROUND: Cytological examination of pleural effusions is very important in the
      diagnosis of malignant lesions. Thoracentesis is the first investigation to be
      performed in a patient with pleural effusion. In this study, we aimed to compare
      traditional with cell block methods for diagnosis of lung disease accompanied by
      pleural effusion. MATERIALS AND METHODS: A total of 194 patients with exudative
      pleural effusions were included. Ten mililiters of fresh pleural fluid were
      obtained by thoracentesis from all patients in the initial evaluation. The
      samples gathered were divided to two equal parts, one for conventional
      cytological analysis and the other for analysis with the cell block technique. In
      cytology, using conventional diagnostic criteria cases were divided into 3
      categories, benign, malignant and undetermined. The cell block sections were
      evaluated for the presence of single tumor cells, papillary or acinar patterns
      and staining with mucicarmine. In the cell block examination, in cases with
      sufficient cell counts histopathological diagnosis was performed. RESULTS: Of the
      total undergoing conventional cytological analyses, 154 (79.4%)were reported as
      benign, 33 (17%) as malignant and 7 (3.6%) as suspicious of malignancy. With the
      cell block method the results were 147 (75.8%) benign, 12 (6.2%) metastatic, 4
      (2.1%) squamous cell carcinoma, 18 (9.3%) adenocarcinoma, 5 (2.6%) large cell
      carcinoma, 2 (1%) mesothelioma, 3 (1.5%) small cell carcinoma, and 3 (1.5%)
      lymphoma. CONCLUSIONS: Our study confirmed that the cell block method increases
      the diagnostic yield with exudative pleural effusions accompanying lung cancer.

PMID- 25854406
TI  - Silencing of Rac3 inhibits proliferation and induces apoptosis of human lung
      cancer cells.
AB  - BACKGROUND: Rac3, a member of the Rac family of small guanosine triphosphatases
      (GTPases), regulates a variety of cell functions, including the organization of
      the cytoskeleton, cell migration, and invasion. Overexpression of Rac3 has been
      reported in several human cancers. However, the role of Rac3 in lung cancer (LC)
      has not been determined in detail. The purpose of this study was to investigate
      the effect of silencing of Rac3 expression in human LC cells and the consequences
      for cell survival. MATERIALS AND METHODS: Lentivirus small hairpin RNA (shRNA)
      interference techniques were utilized to knock down the Rac3 gene. Gene and
      protein expression was quantified by quantitative real-time polymerase chain
      reaction (qRT-PCR) and Western blotting. LC cell apoptosis was examined by
      annexin V-APC /propidium iodide staining. RESULTS: Efficient silencing of Rac3
      strongly inhibited A549 cell proliferation and colony formation ability, and
      significantly decreased tumor growth. Moreover, flow cytometry analysis showed
      that knockdown of Rac3 led to G2/M phase cell cycle arrest as well as an excess
      accumulation of cells in the G1 and S phase. CONCLUSIONS: Thus, functional
      analysis using shRNAs revealed a critical role for Rac3 in the tumor growth of LC
      cells. shRNA silencing of Rac3 could provide an effective strategy to treat LC.

PMID- 25854407
TI  - Survival rates of cervical cancer patients in Malaysia.
AB  - Cervical cancer is the most common malignant cancer of the female reproductive
      organs worldwide. Currently, cervical cancer can be prevented by vaccination and
      detected at an early stage via various screening methods. Malaysia, as a
      developing country faces a heavy disease burden of cervical cancer as it is the
      second most common cancer among Malaysian women. This population based study was
      carried out to fulfil the primary aim of determining the survival rates of
      Malaysian women with cervical cancer and associated factors. Data were obtained
      from two different sources namely, the Malaysian National Cancer Registry (MNCR)
      and National Health Informatics Centre (NHIC) from 1st January 2000 to 31st
      December 2005. Kaplan Meier analyses were conducted to identify the overall
      survival rates and median survival time. Differences in survival among different
      ethnic and age group were compared using the log-rank test. A total of 5,859
      patients were included. The median survival time for cervical cancer in this
      study was 65.8 months and the 5-year survival rate was 71.1%. The overall
      observed survival rates at 1, 3 and 5 years were 94.1%, 79.3% and 71.1%
      respectively. The log-rank test finding also showed that there were significant
      differences in the 5-year survival rate among different ethnic groups. Malays had
      the lowest survival rate of 59.2% followed by Indians (69.5%) and Chinese
      (73.8%). The overall 5-year survival rate among patients with cervical cancer in
      Malaysia is relatively good. Age and ethnic groups remain as significant
      determining factors for cervical cancer survival rate.

PMID- 25854408
TI  - The TP53 intron 6 G13964C polymorphism and risk of thyroid and breast cancer
      development in the Iranian Azeri population.
AB  - BACKGROUND: TP53 mutations are the most common genetic alterations in human
      cancers. There are also several polymorphisms in both exons and introns of TP53
      that may influence its anti-tumor functions and increase the risk of cancer
      development. Associations of the TP53 intron 6 G13964C polymorphism with
      increased risk of development of several cancers have been investigated in
      numerous studies, but the results were controversial and conflicting. In this
      study, we aimed to investigate the probable association of this polymorphism with
      risk of both thyroid and breast cancers among the Iranian-Azeri population.
      MATERIALS AND METHODS: We performed two separate case control studies on
      associations of the intron 6 polymorphism with two different kinds of cancer. In
      one case-control study, a total of 75 patients with thyroid carcinoma and 180
      controls were analyzed and the other study included 170 patients with breast
      cancer and 135 healthy women. The intron 6 genotype was determined by RFLP-PCR
      and the SPSS 16 program was applied for data analysis. RESULTS: For thyroid
      cancer, the frequencies of GG genotype were 96.0% in patients and 93.3% in
      controls. The GC genotype had a frequency of 4.0% in patients and 6.7% in
      controls. In the study on breast cancer, the frequency of GG and GC genotypes in
      patients were 95.3% and 4.7%, respectively. In breast related control group, the
      frequency of GG genotype was 93.3% and the frequency of GC genotype was 6.7%.
      None of the cases and controls had the CC genotype. CONCLUSIONS: There was no
      significant association between the TP53 intron 6 G13964C polymorphism and risk
      of development of both thyroid and breast cancer in Iranian-Azeri patients.

PMID- 25854409
TI  - Expression of cancer-testis antigens in stem cells: is it a potential drawback or
      an advantage in cancer immunotherapy.
AB  - Cancer-testis antigens (CTAs) are a group of tumor associated antigens with a
      restricted expression pattern in normal gametogenic tissues but expression in a
      broad range of malignancies. Their expression pattern has made them potential
      targets for immunotherapy. However, expression of some of these antigens has been
      demonstrated in normal stem cells as well as cancer stem cells (CSCs). As CSCs
      have been shown to be sources of metastasis and tumor recurrence, novel therapies
      are being focused on their eradication. On the other hand, CTA expression in
      normal stem cells raises the possibility that CTA based immunotherapies cause
      side effects in normal tissues. 

PMID- 25854410
TI  - In regard to Wang et al on long-term outcomes following D2 gastrectomy for early
      gastric cancer.

PMID- 25854411
TI  - The Pseudomonas Quinolone Signal Inhibits Biofilm Development of Streptococcus
      mutans.
AB  - Bacteria often thrive in natural environments through a sessile mode of growth,
      known as the biofilm. Biofilms are well-structured communities and their
      formation is tightly regulated. However, the mechanisms by which interspecies
      interactions alter the formation of biofilms have not yet been elucidated in
      detail. We herein demonstrated that a quorum-sensing signal in Pseudomonas
      aeruginosa (the Pseudomonas quinolone signal; PQS) inhibited biofilm formation by
      Streptococcus mutans. Although the PQS did not affect cell growth, biofilm
      formation was markedly inhibited. Our results revealed a unique role for this
      multifunctional PQS and also indicated its application in the development of
      prophylactic agents against caries-causing S. mutans. 

PMID- 25854412
TI  - Designed synthesis of aptamer-immobilized magnetic mesoporous silica/Au
      nanocomposites for highly selective enrichment and detection of insulin.
AB  - We designed and synthesized aptamer-immobilized magnetic mesoporous silica/Au
      nanocomposites (MMANs) for highly selective detection of unlabeled insulin in
      complex biological media using MALDI-TOF MS. The aptamer was easily anchored onto
      the gold nanoparticles in the mesochannels of MMANs with high capacity for highly
      efficient and specific enrichment of insulin. With the benefit from the size
      exclusion effect of the mesoporous silica shell with a narrow pore size
      distribution (~2.9 nm), insulin could be selectively detected despite
      interference from seven untargeted proteins with different size dimensions. This
      method exhibited an excellent response for insulin in the range 2-1000 ng mL(-1).
      Moreover, good recoveries in the detection of insulin in 20-fold diluted human
      serum were achieved. We anticipate that this novel method could be extended to
      other biomarkers of interest and potentially applied in disease diagnostics. 

PMID- 25854413
TI  - The effects of periodontal therapy on serum and salivary leptin levels in chronic
      periodontitis patients with normal body mass index.
AB  - SUMMARY: Leptin concentrations are altered in favour of pro health after
      periodontal therapy. BACKGROUND: Leptin, a non-glycosylated peptide hormone, not
      only maintains fat stores, but is also an integral part of host defense
      repertoire. Leptin levels have been found to be altered in an array of
      inflammatory diseases including chronic periodontitis (CP), but the role of non
      surgical periodontal therapy (NSPT) in altering the leptin concentrations in
      saliva and serum of CP patients is yet to be ascertained. The aim of the present
      study is to quantify leptin levels in CP patients having normal body mass index
      (BMI) pre-therapy as compared to periodontally healthy controls and to address
      whether successful NSPT alters leptin concentration in serum and saliva.
      MATERIALS AND METHODS: Twenty-two saliva (modified draining method) and serum
      samples (by venipuncture) were collected from CP patients with normal BMI (n =
      22), before and at 4 and 12 weeks after completion of NSPT, and periodontally
      healthy, age- and gender-matched controls (n = 22). Leptin levels were estimated
      using enzyme linked immunosorbent assay kits. RESULTS: At baseline, CP patients
      had significantly different periodontal clinical parameters and the leptin
      concentrations in saliva of CP patients were found to be significantly lower than
      periodontally healthy volunteers (4710.10 +/- 1133.21 vs 8721.10 +/- 1019.58
      pg/ml) (p < 0.05), whereas in serum the leptin concentrations were significantly
      higher than healthy controls (10749 +/- 2062.24 vs 8085.00 +/- 2859.68 pg/ml).
      Significant improvement in periodontal parameters, serum and salivary leptin
      levels were observed in CP patients at 4 and 12 weeks post-therapy (p < 0.01).
      CONCLUSION: Altered concentrations of leptin in serum and saliva are observed in
      CP patients which can be restored in favor of health after periodontal therapy.

PMID- 25854414
TI  - Comparing uni-modal and multi-modal therapies for improving writing in acquired
      dysgraphia after stroke.
AB  - Writing therapy studies have been predominantly uni-modal in nature; i.e., their
      central therapy task has typically been either writing to dictation or copying
      and recalling words. There has not yet been a study that has compared the effects
      of a uni-modal to a multi-modal writing therapy in terms of improvements to
      spelling accuracy. A multiple-case study with eight participants aimed to compare
      the effects of a uni-modal and a multi-modal therapy on the spelling accuracy of
      treated and untreated target words at immediate and follow-up assessment points.
      A cross-over design was used and within each therapy a matched set of words was
      targeted. These words and a matched control set were assessed before as well as
      immediately after each therapy and six weeks following therapy. The two
      approaches did not differ in their effects on spelling accuracy of treated or
      untreated items or degree of maintenance. All participants made significant
      improvements on treated and control items; however, not all improvements were
      maintained at follow-up. The findings suggested that multi-modal therapy did not
      have an advantage over uni-modal therapy for the participants in this study.
      Performance differences were instead driven by participant variables. 

PMID- 25854415
TI  - Acquired factor V deficiency in myeloproliferative neoplasms: a Mayo Clinic
      series of 33 patients.

PMID- 25854416
TI  - Contact properties of field-effect transistors based on indium arsenide nanowires
      thinner than 16 nm.
AB  - With the scaling down of field effect transistors (FETs) to improve performance,
      the contact between the electrodes and the channel becomes more and more
      important. Contact properties of FETs based on ultrathin InAs NWs (with the
      diameter ranging from sub-7 nm to 16 nm) are investigated here. Chromium (Cr) and
      nickel (Ni) are proven to form ohmic contact with the ultrathin InAs NWs, in
      contrast to a recent report (Razavieh A et al ACS Nano 8 6281). Furthermore, the
      contact resistance is found to depend on the NW diameter and the contact metals,
      which between Cr and InAs NWs increases more rapidly than that between Ni and
      InAs NWs when the NW diameter decreases. The origins of the contact resistance
      difference for the two kinds of metals are studied and NixInAs is believed to
      play an important role. Based on our results, it is advantageous to use Ni as
      contact metal for ultrathin NWs. We also observe that the FETs are still working
      in the diffusive regime even when the channel length is scaled down to 50 nm. 

PMID- 25854417
TI  - Donation intensity and metabolic syndrome in active whole-blood donors.
AB  - BACKGROUND AND OBJECTIVES: Increased iron and metabolic syndrome (MetS) go hand
      in hand. Frequent blood donation depletes iron stores. This study investigates
      whether high-intensity blood donation is associated with lower MetS prevalence
      compared with low-intensity blood donation, and whether iron acts as an
      intermediary factor. MATERIALS AND METHODS: A random sample of 422 male and 211
      female active whole-blood donors >=45 years of age was included in a cross
      sectional study. Lipids, glucose and iron parameters were measured after
      overnight fasting. MetS was defined according to the joint interim statement of
      the International Diabetes Federation Task Force on Epidemiology and Prevention.
      Three groups of donation intensity were created by sex-specific tertiles of
      donation frequency per year and duration of donor career. RESULTS: MetS was
      present in 22.9% of donors. Prevalence of MetS was 1.46 (95% confidence interval
      [CI]: 0.93-2.30) times higher in men with high donation intensity, whereas in
      women MetS prevalence was 2.14 (95% CI: 0.94-4.86) times higher in donors with
      high donation intensity compared with those with low donation intensity. In men,
      increased prevalence of MetS was mainly associated with higher ferritin, whereas
      high hepcidin predominantly affected MetS prevalence in women. CONCLUSION: High
      intensity blood donation is not associated with a decreased prevalence of MetS.
      In men and women, different iron parameters are associated with MetS prevalence.
      The temporal relationship between blood donation, iron and MetS, and gender
      differences herein need to be explored in future research.

PMID- 25854419
TI  - Malignant melanoma showing a rapid response to nivolumab.
AB  - Malignant melanoma is a highly aggressive skin tumour, with a recent rise in
      incidence. Nivolumab is a recently developed anti-programmed cell death-1 immune
      checkpoint inhibitor and its usage has resulted in a significant improvement in
      the overall survival of patients with metastatic melanomas. We report a case of
      advanced melanoma that showed a significant and rapid response to nivolumab
      treatment. The patient displayed multiple melanoma-associated vitiligo prior to
      treatment; this symptom was theorised to indicate potentially immunoreactive
      melanoma and the need for nivolumab. In addition, interferon-beta was injected
      prior to nivolumab treatment. The significant rapid response to nivolumab
      suggested the induction of a marked immune response against melanoma by
      interferon-beta. Therefore, interferon-beta could be a useful and effective
      adjuvant for nivolumab therapy. 

PMID- 25854418
TI  - Cardiac regenerative potential of cardiosphere-derived cells from adult dog
      hearts.
AB  - The regenerative potential of cardiosphere-derived cells (CDCs) for ischaemic
      heart disease has been demonstrated in mice, rats, pigs and a recently completed
      clinical trial. The regenerative potential of CDCs from dog hearts has yet to be
      tested. Here, we show that canine CDCs can be produced from adult dog hearts.
      These cells display similar phenotypes in comparison to previously studied CDCs
      derived from rodents and human beings. Canine CDCs can differentiate into
      cardiomyocytes, smooth muscle cells and endothelial cells in vitro. In addition,
      conditioned media from canine CDCs promote angiogenesis but inhibit cardiomyocyte
      death. In a doxorubicin-induced mouse model of dilated cardiomyopathy (DCM),
      intravenous infusion of canine CDCs improves cardiac function and decreases
      cardiac fibrosis. Histology revealed that injected canine CDCs engraft in the
      mouse heart and increase capillary density. Out study demonstrates the
      regenerative potential of canine CDCs in a mouse model of DCM. 

PMID- 25854420
TI  - Social functioning and socioeconomic changes after introduction of regular
      dialysis treatment and impact of dialysis modality: a multi-centre survey of
      Japanese patients.
AB  - AIM: Patient socialization and preservation of socioeconomic status are important
      patient-centred outcomes for those who start dialysis, and retention of
      employment is a key enabler. This study examined the influence of dialysis
      inception and modality upon these outcomes in a contemporary Japanese cohort.
      METHODS: We conducted a survey of prevalent chronic dialysis patients from 5
      dialysis centres in Japan. All patients who had been on peritoneal dialysis (PD)
      since dialysis inception were recruited, and matched with a sample of those on in
      centre haemodialysis (ICHD). We assessed patients' current social functioning
      (Short Form 36 Health Survey), and evaluated changes to patient employment
      status, annual income, and general health condition from the pre-dialysis period
      to the current time. RESULTS: A total of 179 patients were studied (102 PD and 77
      ICHD). There were no differences in social functioning by modality. Among them,
      113 were employed in the pre-dialysis period with no difference by modality. Of
      these, 22% became unemployed after dialysis inception, with a corresponding
      decline in average working hours and annual income. The odds of unemployment
      after dialysis inception were 5.02 fold higher in those on ICHD compared to those
      on PD, after adjustment for covariates. There were no changes for those who were
      already unemployed in the pre-dialysis period. CONCLUSIONS: Employment status is
      significantly hampered by dialysis inception, although PD was associated with
      superior retention of employment and greater income compared to ICHD. This
      supports a positive role for PD in preservation of socioeconomic status and
      potentially other patient-centred outcomes.

PMID- 25854421
TI  - Pharmacological evidence that 5-HT1D activation induces renal vasodilation by NO
      pathway in rats.
AB  - 5-HT is a powerful vasoconstrictor substance in renal vasculature (mainly by 5
      HT2 activation). Nevertheless, 5-HT is notable for its dual cardiovascular
      effects, producing both vasodilator and vasoconstrictor actions. This study aimed
      to investigate whether, behind the predominant serotonergic vasoconstrictor
      action, THE 5-HT system may exert renal vasodilator actions, and, if so,
      characterize the 5-HT receptors and possible indirect pathways. Renal perfusion
      pressure (PP), systemic blood pressure (SBP) and heart rate (HR) measurement in
      in situ autoperfused rat kidney was determined in phenylephrine infused rats.
      Intra arterial (i.a.) bolus administration of 5-HT (0.00000125-0.1 MUg/kg)
      decreased renal PP in the presence of a phenylephrine continuous infusion
      (phenylephrine-infusion group), without modifying SBP or HR. These vasodilator
      responses were potentiated by 5-HT2 antagonism (ritanserin, 1 mg/kg i.v.),
      whereas the responses were abolished by 5-HT1 /7 antagonist (methiothepin, 100
      MUg/kg i.v.) or 5-HT1D antagonist (LY310762, 1 mg/kg i.v.). The i.a.
      administration (0.00000125 to 0.1 MUg/kg) of 5-CT or L-694,247 (5-HT1D agonist)
      mimicked 5-HT vasodilator effect, while other agonists (1-PBG, alpha-methyl-5-HT,
      AS-19 (5-HT7), 8-OH-DPAT (5-HT1A) or CGS-12066B (5-HT1B)) did not alter baseline
      haemodynamic variables. L-694,247 vasodilation was abolished by i.v. bolus of
      antagonists LY310762 (5-HT1D, 1 mg/kg) or L-NAME (nitric oxide, 10 mg/kg), but
      not by i.v. bolus of indomethacin (cyclooxygenase, 2 mg/kg) or glibenclamide (ATP
      dependent K(+) channel, 20 mg/kg). These outcomes suggest that 5-HT1D activation
      produces a vasodilator effect in the in situ autoperfused kidney of phenylephrine
      infusion rats mediated by the NO pathway.

PMID- 25854422
TI  - Safety of radiation exposure after radiosynovectomy in paediatric patients with
      haemophilia.
AB  - Many paediatric patients with haemophilia who might benefit from radiosynovectomy
      (RS) for the control of synovitis do not undergo the procedure as there is
      controversy in the literature regarding the safety of radiation exposure after
      two cases of acute lymphocytic leukaemia in children with haemophilia treated
      with (32) P RS were reported. The purpose of this review was to analyse the
      safety of RS in paediatric patients with haemophilia and provide a risk-benefit
      assessment, which practitioners could apply to their patients. Children
      undergoing knee RS receive a radiation dose of approximately 0.74 mSv (90
      megabecquerels-MBq) and elbow and ankle RSs a dose of approximately 0.32 mSv (30
      40 MBq). The radiation dose from natural sources is approximately 2 mSv and the
      recommended limit for patients (apart from natural sources) is 1 mSv per year.
      The lifetime cancer risk increases about 0.5% per 100 mSv per year. Considering
      the risks and benefits of RS, the authors recommend that clinicians consider this
      procedure in children with inhibitors or in patients without inhibitors when
      bleeding is recurrent and persistent despite aggressive factor replacement. 

PMID- 25854423
TI  - Health Information Technology Adoption in the Emergency Department.
AB  - OBJECTIVE: To describe the trend in health information technology (IT) systems
      adoption in hospital emergency departments (EDs) and its effect on ED efficiency
      and resource use. DATA SOURCES: 2007-2010 National Hospital Ambulatory Medical
      Care Survey - ED Component. STUDY DESIGN: We assessed changes in the percent of
      visits to EDs with health IT capability and the estimated effect on waiting time
      to see a provider, visit length, and resource use. PRINCIPAL FINDINGS: The
      percent of ED visits that took place in an ED with at least a basic health IT or
      an advanced IT system increased from 25.2 and 3.1 percent in 2007 to 69.1 and
      30.6 percent in 2010, respectively (p < .05). Controlling for ED fixed effects,
      waiting times were reduced by 6.0 minutes in advanced IT-equipped EDs (p < .05),
      and the number of tests ordered increased by 9 percent (p < .01). In models using
      a 1-year lag, advanced systems also showed an increase in the number of
      medications and images ordered per visit. CONCLUSIONS: Almost a third of visits
      now occur in EDs with advanced IT capability. While advanced IT adoption may
      decrease wait times, resource use during ED visits may also increase depending on
      how long the system has been in place. We were not able to determine if these
      changes indicated more appropriate care.

PMID- 25854424
TI  - Sustained impact of UK FAST-test public education on response to stroke: a
      population-based time-series study.
AB  - BACKGROUND: Urgent assessment is essential after stroke. Several countries have
      had public education campaigns, based on the FAST (Face-Arm-Speech-Time) test to
      reduce delays in seeking attention. However, the impact of these campaigns on
      patient behavior is uncertain. METHODS: We prospectively determined patient
      behavior after incident major stroke (NIHSS > 3) in a UK population based study
      (Oxford Vascular Study) before (2002-2008) and after (2009-2013) introduction of
      the FAST TV-campaign and assessed any sustained impact of campaign continuation.
      RESULTS: Among 668 consecutive patients with major stroke, medical attention was
      sought by a bystander in 553 (89.6%). Patients were more likely to present
      directly to emergency services (OR = 2.18, 95%CI:1.54-3.09, P < 0.0001) after the
      campaign and to arrive at hospital within 3 h (OR = 2.18, 1.55-3.06, P < 0.0001).
      Median [IQR] time to seeking attention fell from 53 [15-265] to 31 [7-120]
      minutes (P = 0.005) and median time to hospital arrival from 185 [88-885] to 119
      [78-256] minutes (P < 0.0001). On time-series analysis improvements in hospital
      arrival within 3 h and use of emergency medical services were significantly
      associated to initiation of the campaign (aOR = 3.11, 1.53-6.29, P = 0.002; and
      2.22, 1.05-4.67, P = 0.036, respectively), independent of trend, age, sex,
      ethnicity, educational level, social class, prior stroke and stroke severity, and
      have been sustained to 2013. CONCLUSION: Delays to seeking and receiving medical
      attention after major stroke in the UK. fell strikingly in 2009, coinciding with
      the start of the FAST TV campaign. That medical attention was sought by a
      bystander in nearly 90% of cases illustrates the importance of mass-media public
      education rather than focused programs in high-risk groups for major stroke.

PMID- 25854425
TI  - Enzymatic synthesis of magnetic nanoparticles.
AB  - We report the first in vitro enzymatic synthesis of paramagnetic and
      antiferromagnetic nanoparticles toward magnetic ELISA reporting. With our
      procedure, alkaline phosphatase catalyzes the dephosphorylation of l-ascorbic-2
      phosphate, which then serves as a reducing agent for salts of iron, gadolinium,
      and holmium, forming magnetic precipitates of Fe45+/-14Gd5+/-2O50+/-15 and Fe42+/
      4Ho6+/-4O52+/-5. The nanoparticles were found to be paramagnetic at 300 K and
      antiferromagnetic under 25 K. Although weakly magnetic at 300 K, the room
      temperature magnetization of the nanoparticles found here is considerably greater
      than that of analogous chemically-synthesized LnxFeyOz (Ln = Gd, Ho) samples
      reported previously. At 5 K, the nanoparticles showed a significantly higher
      saturation magnetization of 45 and 30 emu/g for Fe45+/-14Gd5+/-2O50+/-15 and
      Fe42+/-4Ho6+/-4O52+/-5, respectively. Our approach of enzymatically synthesizing
      magnetic labels reduces the cost and avoids diffusional mass-transfer limitations
      associated with pre-synthesized magnetic reporter particles, while retaining the
      advantages of magnetic sensing. 

PMID- 25854426
TI  - In vitro cytotoxic evaluation of MgO nanoparticles and their effect on the
      expression of ROS genes.
AB  - Water-dispersible MgO nanoparticles were tested to investigate their cytotoxic
      effects on oxidative stress gene expression. In this in vitro study, genes
      related to reactive oxygen species (ROS), glutathione S-transferase (GST) and
      catalase, were quantified using real-time polymerase chain reactions (molecular
      level) and molecular beacon technologies (cellular level). The monodispersed MgO
      nanoparticles, 20 nm in size, were used to treat human cancer cell lines (liver
      cancer epithelial cells) at different concentrations (25, 75 and 150 ug/mL) and
      incubation times (24, 48 and 72 h). Both the genetic and cellular cytotoxic
      screening methods produced consistent results, showing that GST and catalase ROS
      gene expression was maximized at 150 ug/mL nanoparticle treatment with 48 h
      incubation. However, the genotoxic effect of MgO nanoparticles was not
      significant compared with control experiments, which indicates its significant
      potential applications in nanomedicine as a diagnostic and therapeutic tool. 

PMID- 25854427
TI  - Insulin induces phosphorylation of serine residues of translationally controlled
      tumor protein in 293T cells.
AB  - Insulin induces the activation of Na,K-ATPase while translationally controlled
      tumor protein (TCTP) inhibits this enzyme and the associated pump activity.
      Because binding of insulin with its membrane receptor is known to mediate the
      phosphorylation of multiple intracellular proteins, phosphorylation of TCTP by
      insulin might be related to the sodium pump regulation. We therefore examined
      whether insulin induces TCTP phosphorylation in embryonic kidney 293T cells.
      Using immunoprecipitation and Western blotting, we found that insulin
      phosphorylates serine (Ser) residues of TCTP. Following fractionation of the
      insulin-treated cells into cytosol and membrane fractions, phosphorylated TCTP at
      its Ser residue (p-Ser-TCTP) was detected exclusively in the cytosolic part and
      not in the membrane fraction. Phosphorylation of TCTP reached maximum in about 10
      min after insulin treatment in 293T cells. In studies of cell-type specificity of
      insulin-mediated phosphorylation of TCTP, insulin did not phosphorylate TCTP in
      HeLa cells. Computational prediction and immunoprecipitation using several
      constructs having Ser to Ala mutation at potential p-Ser sites of TCTP revealed
      that insulin phosphorylated the serine-9 and -15 residues of TCTP. Elucidations
      of how insulin-mediated TCTP phosphorylation promotes Na,K-ATPase activation, may
      offer potential therapeutic approaches to diseases associated with vascular
      activity and sodium pump dysregulation. 

PMID- 25854428
TI  - Poly-gamma-glutamic acid induces apoptosis via reduction of COX-2 expression in
      TPA-induced HT-29 human colorectal cancer cells.
AB  - Poly-gamma-glutamic acid (PGA) is one of the bioactive compounds found in
      cheonggukjang, a fast-fermented soybean paste widely utilized in Korean cooking.
      PGA is reported to have a number of beneficial health effects, and interestingly,
      it has been identified as a possible anti-cancer compound through its ability to
      promote apoptosis in cancer cells, although the precise molecular mechanisms
      remain unclear. Our findings demonstrate that PGA inhibits the pro-proliferative
      functions of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), a
      known chemical carcinogen in HT-29 human colorectal cancer cells. This inhibition
      was accompanied by hallmark apoptotic phenotypes, including DNA fragmentation and
      the cleavage of poly (ADP-ribose) polymerase (PARP) and caspase 3. In addition,
      PGA treatment reduced the expression of genes known to be overexpressed in
      colorectal cancer cells, including cyclooxygenase 2 (COX-2) and inducible nitric
      oxide synthase (iNOS). Lastly, PGA promoted activation of 5' adenosine
      monophosphate-activated protein (AMPK) in HT-29 cells. Taken together, our
      results suggest that PGA treatment enhances apoptosis in colorectal cancer cells,
      in part by modulating the activity of the COX-2 and AMPK signaling pathways.
      These anti-cancer functions of PGA make it a promising compound for future study.

PMID- 25854431
TI  - What's in this Issue?

PMID- 25854429
TI  - A new and practical synthetic method for the synthesis of 6-O-methyl
      scutellarein: one metabolite of scutellarin in vivo.
AB  - Scutellarin (1) has been used for the treatment of angina pectoris, cerebral
      infarction and coronary heart disease with a large market share in China.
      Pharmacokinetic studies on scutellarin showed that scutellarin (1) is readily
      converted into its metabolites in vivo. In this paper, a new and practical
      synthetic method for the synthesis of 6-O-methyl-scutellarein (3) (one metabolite
      of scutellarin in vivo) is reported. The benzyl bromide was firstly used to
      selectively replace the acetyl group at C-7 in 7, and was then used to protect
      the hydroxy groups at C-4' in 10, 6-O-methyl-scutellarein (3) is obtained in high
      yield through these methods. 

PMID- 25854430
TI  - Isolation and heterologous expression of a polygalacturonase produced by Fusarium
      oxysporum f. sp. cubense race 1 and 4.
AB  - Fusarium wilt (Panama disease) caused by Fusarium oxysporum f. sp. cubense (FOC)
      represents a significant threat to banana (Musa spp.) production. Musa AAB is
      susceptible to Race 1 (FOC1) and Race 4 (FOC4), while Cavendish Musa AAA is found
      to be resistant to FOC1 but still susceptible to Race 4. A polygalacturonase
      (PGC3) was purified from the supernatant of Fusarium oxysporum f. sp. cubense
      race 4 (FOC4), which is the pathogen of Fusarium wilt. PGC3 had an apparent
      molecular weight of 45 kDa according to SDS-PAGE. The enzyme hydrolyzed
      polygalacturonic acid in an exo-manner, as demonstrated by analysis of
      degradation products. The Km and Vmax values of PGC3 from FOC4 were determined to
      be 0.70 mg.mL-1 and 101.01 Units.mg.protein-1.min-1, respectively. Two pgc3 genes
      encoding PGC3 from FOC4 and FOC1, both genes of 1368 bp in length encode 456
      amino-acid residues with a predicted signal peptide sequence of 21 amino acids.
      There are 16 nucleotide sites difference between FOC4-pgc3 and FOC1-pgc3, only
      leading to four amino acid residues difference. In order to obtain adequate
      amounts of protein required for functional studies, two genes were cloned into
      the expression vector pPICZaA and then expressed in Pichia pastoris strains of
      SMD1168. The recombinant PGC3, r-FOC1-PGC3 and r-FOC4-PGC3, were expressed and
      purified as active proteins. The optimal PGC3 activity was observed at 50 
      degrees C and pH 4.5. Both recombinant PGC3 retained >40% activity at pH 3-7 and
      >50% activity in 10-50  degrees C. Both recombinant PGC3 proteins could induce a
      response but with different levels of tissue maceration and necrosis in banana
      plants. In sum, our results indicate that PGC3 is an exo-PG and can be produced
      with full function in P. pastoris. 

PMID- 25854432
TI  - Improving patient safety by innovation.

PMID- 25854433
TI  - Supporting patients' and families' religious and spiritual needs in ICU--can we
      do more?

PMID- 25854438
TI  - Cardiovascular examination in children: the risk of overdiagnosis.

PMID- 25854439
TI  - Heart rate and B-blockade in stable coronary artery disease in Greece.
AB  - INTRODUCTION: Heart rate (HR) is a strong prognostic indicator in patients with
      coronary artery disease (CAD). However, there is only limited evidence on HR and
      the use of b-blockers in patients with CAD in contemporary clinical practice.
      METHODS: CLARIFY is an international, prospective, observational, longitudinal
      registry of outpatients with stable CAD, defined as prior myocardial infarction
      or revascularization procedure, evidence of coronary stenosis >50%, or chest pain
      associated with proven myocardial ischemia. A total of 33,283 patients from 45
      countries were enrolled between November 2009 and July 2010; of these, 559
      patients were enrolled in Greece (age 62.3 +/- 10.6 years, 84.44% men). RESULTS:
      HR measured by pulse was 68.3 +/- 10.2 bpm and by electrocardiogram 67.6 +/-
      10.9, with an excellent correlation (r=0.91, p<0.001). Overall, 42.8% had HR70
      bpm. B-blockers were prescribed in 74.2% of patients. Resting HR by pulse on b
      blocker was 67.8 bpm and without b-blocker 69.6 bpm (p=0.069). HR70 bpm was
      independently associated with a lack of physical activity, higher systolic blood
      pressure, and a higher prevalence of asthma or chronic obstructive pulmonary
      disease and carotid artery disease. CONCLUSION: Despite the use of HR lowering
      agents, the percentage of patients with HR70 bpm was high. It is likely that we
      can further improve HR control in Greek patients with stable CAD by both
      increasing the prescription of b-blockers and up-titrating their dose, as well as
      by using and up-titrating other available HR lowering agents.

PMID- 25854440
TI  - Bilateral symmetry of local inflammatory activation in human carotid
      atherosclerotic plaques.
AB  - INTRODUCTION: Only a few studies have investigated the structural and functional
      characteristics of carotid arteries bilaterally. Furthermore, there is
      controversy as to whether inflammation in paired vascular beds is a local or
      systemic phenomenon. We aimed to examine, in patients with coronary artery
      disease, whether intra-subject left and right carotid arteries have similar
      inflammatory status, as determined non-invasively by microwave radiometry (MWR).
      METHODS: Consecutive patients (n=200) with significant coronary artery disease
      were evaluated via an ultrasound echo-colour Doppler (US-ECD) study of both
      carotid arteries and temperature measurements with MWR. During thermography,
      thermal heterogeneity (DeltaT) was defined as the maximum temperature along the
      carotid artery minus the minimum temperature. RESULTS: Mean T was similar between
      the left and right carotid arteries (0.78 +/- 0.48 vs. 0.84 +/- 0.52 degrees C,
      p=0.12). Mean right intima-media thickness (IMT) was greater compared to mean
      left IMT (2.16 +/- 1.20 vs. 1.93 +/- 0.94 mm, p<0.01). In all carotids, there was
      a correlation between left and right carotid plaque DeltaT (R=0.38, p<0.001) and
      between left and right IMT (R=0.48, p<0.001). Independent predictors for the
      presence of bilateral carotid plaques were found to be the extent of coronary
      artery disease, high DeltaT, and therapy with angiotensin II receptor blockers;
      predictors for the presence of high DeltaT bilaterally were bilateral carotid
      plaques, male sex, diabetes mellitus, and hypertension. CONCLUSIONS: There is
      bilateral inflammatory activation in the carotid atherosclerotic lesions of
      patients with coronary artery disease. At this stage of carotid disease, arterial
      hypertension and diabetes mellitus are more strongly correlated with bilateral
      functional abnormalities in carotid plaques than with structural changes.

PMID- 25854441
TI  - Early and late optical coherence tomography findings following everolimus-eluting
      bioresorbable vascular scaffold implantation in myocardial infarction: a
      preliminary report.
AB  - INTRODUCTION: Although bioresorbable vascular scaffolds (BVS) have been used with
      promising results in patients with stable and unstable angina, little is known
      about the acute vascular response following BVS implantation in myocardial
      infarction. We present angiographic and OCT findings from the first patients
      undergoing bioresorbable vascular scaffold (BVS) implantation for non-ST
      elevation myocardial infarction (NSTEMI) or ST-elevation myocardial infarction
      (STEMI) in our institution. METHODS: The first 5 patients with NSTEMI and the
      first 5 patients with STEMI who underwent BVS implantation in our institution,
      followed by optical coherence tomography (OCT) imaging of the treated culprit
      vessel, were included in this series. All patients underwent angiographic
      analysis pre- and post- BVS implantation, as well as OCT analysis, including
      qualitative and quantitative assessment. RESULTS: Implantation was successful in
      all cases, as assessed by angiography and OCT. There were no cases with coronary
      spasm, distal embolization or no-reflow. No adverse clinical events were recorded
      in any patient at the 6-month follow up. Specific illustrative cases
      demonstrating the challenges of BVS implantation in myocardial infarction are
      presented. CONCLUSIONS: BVS implantation can potentially be used in the setting
      of thrombotic lesions encountered in myocardial infarction; however, the role of
      this treatment approach warrants systematic evaluation in prospective studies.

PMID- 25854442
TI  - Clinical and angiographic characteristics of patients with acute coronary
      syndrome associated with sudden cardiac death.
AB  - INTRODUCTION: Sudden death (SD) is in most cases due to cardiac causes, mainly
      secondary to ischemic heart disease. However, the angiographic characteristics in
      SD survivors in the context of an acute coronary syndrome (ACS) remain
      controversial. The aim of this study was to evaluate the clinical and
      angiographic characteristics of patients who suffered cardiac arrest during an
      ACS. METHODS: We evaluated 46 patients with SD related to ACS, who were divided
      into two groups according to their presentation: an ST-elevation myocardial
      infarction (SD-STEMI) group and a non ST-elevation myocardial infarction (SD
      NSTEMI) group. Consecutive STEMI patients without SD served as a double size
      matched control group. We compared the clinical and angiographic characteristics
      and the in-hospital mortality between groups. RESULTS: Patients in the SD-NSTEMI
      group (n=13) were older and had a higher incidence of hypertension. The left
      anterior descending coronary artery was the most frequent culprit vessel in all
      groups. SD-STEMI patients (n=33) had a higher prevalence of proximal coronary
      culprit segment involvement than did the nonSD STEMI group (75% vs. 36.3%,
      p<0.001). The SD-NSTEMI group was characterized by multivessel and multi-segment
      disease. Outcomes were similar for both SD groups. CONCLUSION: SD in patients
      with NSTEMI occurred in patients who were older, with more cardiovascular risk
      factors, diffuse and multivessel coronary disease, complex coronary lesions, and
      a lower rate of angioplasty success as compared with the STEMI group. SD STEMI
      patients had a significant higher association with proximal coronary acute
      occlusion than STEMI patients without SD.

PMID- 25854443
TI  - Adding fentanyl to etomidate fails to reduce painful recall of external direct
      current cardioversion in adults: a randomised trial.
AB  - INTRODUCTION: External electrical cardioversion under hypnotics, even when
      combined with opioids, has been consistently described as distressing or painful.
      The main objective of the present study was to determine if adding an opioid to a
      hypnotic, in comparison to the same hypnotic alone, would decrease the incidence
      of unpleasant or painful recall during anaesthesia for external electrical
      cardioversion. METHODS: This was a single-centre, prospective, randomised, double
      blinded clinical trial that took place from September 2011 to March 2012. Fifty
      two adult patients with persistent atrial fibrillation, scheduled for external
      direct current cardioversion, were enrolled. Exclusion criteria were age >80
      years, previous cardiac surgery, implanted pacemaker or defibrillator, and
      haemodynamic instability. Patients received intravenously either (group EF)
      fentanyl 50 g and after 60 s etomidate 0.1 mg/kg, or (group E) only etomidate 0.1
      mg/kg. If the patients did not lose their eyelid reflex, repeated doses of
      etomidate 4 mg were given. Cardioversion was attempted with an extracardiac
      biphasic electrical shock from 200 to 300 J, at most three times. The primary
      endpoint was recall of something unpleasant or painful. Secondary outcome
      measures were predictors of the requirement for repeat doses of etomidate, and
      the number of shocks needed. RESULTS: Fifty-one patients (35 male, 16 female),
      aged 62.1 +/- 10.2 years, completed the study. There were no differences between
      group EF and group E regarding recall (unpleasant recall 0 vs. 2 patients,
      p=0.235; painful recall 1 vs. 0 patients, p=0.510). The administration of
      etomidate alone was a significant predictor for subsequent repeated doses of
      etomidate (p=0.049, odds ratio 4.312, 95% confidence interval 1.007-18.460). The
      number of shocks needed to restore sinus rhythm did not differ between the groups
      (p=0.846). CONCLUSIONS: In the present study, the addition of fentanyl to
      etomidate did not diminish distressing or painful experience during anaesthesia
      for external cardioversion.

PMID- 25854444
TI  - Assessment of nursing staff's theoretical knowledge of cardiovascular
      resuscitation in an NHS public hospital.
AB  - INTRODUCTION: The effective provision of cardiopulmonary resuscitation (CPR)
      increases patient survival and reduces in-hospital mortality. Nursing staff, as
      front-line healthcare professionals, are often the first present at
      cardiovascular arrests and respond by providing CPR. Their training has an impact
      on the efficiency of CPR and consequently on health outcomes; thus, assessment of
      their status in that respect may provide useful information for decision making.
      METHODS: A cross-sectional study was undertaken in an NHS hospital in Greece to
      assess the theoretical knowledge of nurses and assistant nurses in relation to
      CPR. The study population surveyed consisted of nurses and assistant nurses of a
      specific public hospital. RESULTS: The study revealed that nursing staff had poor
      theoretical knowledge, with a mean score for correct answers in the written test
      of 50.6 +/- 25.9% and a mean 4.1 +/- 2 correct answers. Fifty-three percent of
      participants reported taking part in a refresher course after attending a first
      course, while only 13.2% had participated in a relevant training program during
      the last 6 months prior to the study. Registered nurses who possessed a
      university (p=0.016) or a technological institution (p<0.001) diploma, achieved
      36.1% and 20.9% higher mean scores, respectively, in the written test in
      comparison to assistant nurses. The vast majority (91.9%) of the participants
      expressed their willingness to participate in CPR training courses. CONCLUSIONS:
      It is crucial for nursing staff to participate in CPR courses in order to refresh
      and update their theoretical knowledge and performance skills and consequently to
      improve the safety and effectiveness of care.

PMID- 25854445
TI  - High furosemide dose has detrimental effects on survival of patients with stable
      heart failure.
AB  - INTRODUCTION: High doses of furosemide for heart failure (HF) have been
      correlated with an increased mortality, though whether they are a marker of
      disease severity or an independent predictor is unknown. We hypothesized that, in
      patients presenting with stable HF, the likelihood of long-term major adverse
      clinical events is increased by higher furosemide doses. METHODS: We
      retrospectively recorded the doses of furosemide prescribed to 173 consecutive,
      clinically stable patients during a first ambulatory HF department visit. The low
      dose group included 103 patients treated with 80 mg and the high-dose group
      included 70 patients treated with >80 mg of furosemide daily. Proportional hazard
      regression analyses were performed with single and multiple variables in search
      of correlates of long-term adverse clinical events. Hazard ratios (HR) and 95%
      confidence intervals (CI) were calculated. RESULTS: The baseline characteristics
      of the 2 groups were similar, except for estimated glomerular filtration rate,
      which was higher in the low- than the high-dose group (72.9 +/- 19.4 vs. 60.8 +/-
      22.0 mL/min/ m2, p<0.001). The 3-year survival free from the composite endpoint
      was significantly higher in the lowdose group than in the high-dose group (93.1%
      vs. 60.0%, p<0.001). By multiple variable analysis, highdose furosemide was an
      independent predictor of an adverse outcome at 3 years (adjusted HR: 15.25; 95%
      CI:1.06-219.39, p=0.045). The incidence of deterioration of renal function and
      episodes of hypokalemia during follow up was also higher in the high furosemide
      dose (73.2% vs. 48.3, p=0.003, and 43.1% vs. 6.5%, p<0.001, respectively).
      CONCLUSIONS: High doses of furosemide administered in order to stabilize HF
      patients and continued thereafter are associated with an adverse clinical
      outcome.

PMID- 25854446
TI  - Urine NGAL as a biomarker of kidney damage after on- and off-pump coronary artery
      bypass graft surgery: a prospective pilot study.
AB  - INTRODUCTION: Acute kidney injury (AKI) is a relatively frequent complication
      after coronary artery bypass graft surgery (CABG). We compared the off- and on
      pump CABG procedures with respect to changes in renal function as reflected by
      levels of urine neutrophil gelatinase-associated lipocalin (UrNGAL). METHODS: In
      a prospective design, we studied patients who underwent CABG, off- or on-pump,
      with respect to changes in glomerular filtration rate (GFR) and UrNGAL pre- and
      postoperatively. UrNGAL was measured using a chemiluminescent microparticle
      immunoassay. We recorded patients' demographics, past medical history, cardiac
      function and laboratory findings. Patients were grouped according to the CABG
      type. RESULTS: Of 72 patients, 31 underwent off-pump and 41 on-pump CABG. The
      mean age was 65.7 +/- 8.1 years and 81.9% were males. Groups were similar with
      respect to the prevalence of hypertension, diabetes, dyslipidaemia, body mass
      index, and smoking at entry. No patient experienced acute renal failure and there
      were no deaths. At both time points, the UrNGAL levels were similar in the two
      groups. Patients in the on-pump group showed a significant improvement in renal
      function 48 hours postoperatively compared to baseline (p<0.001). UrNGAL levels
      decreased significantly 3 hours after surgery in the on-pump group (p=0.001),
      while they tended to decrease in the off-pump group (p=0.057). The overall change
      in UrNGAL did not differ significantly between groups. CONCLUSIONS: According to
      the UrNGAL measurements, neither of the two CABG techniques was superior in terms
      of their effect on postoperative renal function. Renal function significantly
      improved in the on-pump group while UrNGAL levels decreased after surgery in the
      same group.

PMID- 25854447
TI  - Imaging of acute aortic syndrome: advantages, disadvantages and pitfalls.

PMID- 25854448
TI  - Giant right atrium late after left-sided heartvalve replacement: re-do cardiac
      surgery for severe tricuspid regurgitation.

PMID- 25854449
TI  - Calcified apical intramyocardial hematoma in an asymptomatic middle-aged man: a
      multimodality imaging approach.

PMID- 25854450
TI  - Can univentricular heart be associated with "rigid body rotation"? A case from
      the threedimensional speckle-tracking echocardiographic MAGYAR-path study.

PMID- 25854451
TI  - Broad goals of the HCS for the reduction of mortality and morbidity.

PMID- 25854452
TI  - Cardiology in the next two decades: just imagine.

PMID- 25854453
TI  - A Primer for Working in Campus Mental Health: A System of Care.

PMID- 25854454
TI  - Stigma and empathy: sex workers as educators of medical students.

PMID- 25854455
TI  - Normal saline versus balanced-salt solution as intravenous fluid therapy during
      neurosurgery: effects on acid-base balance and electrolytes.
AB  - BACKGROUND: This prospective, randomized controlled study compared the changes in
      acid-base balance and serum electrolytes with the use of intravenous balanced and
      non-balanced crystalloid solutions intraoperatively during elective neurosurgery.
      METHODS: Thirty consented adult patients who underwent craniotomy were randomly
      allocated into two groups of 15 patients each. The non-balanced group received
      0.9% normal saline while the balanced group received Sterofundin(r)ISO as the
      intraoperative fluid for maintenance. Biochemical indices for acid-base balance
      and serum electrolytes were analyzed periodically. RESULTS: In the non-balanced
      group, significant changes were noted in the pH, base excess and bicarbonate
      values over time compared to its respective baseline values (P<0.01). Four
      patients (27.7%) also developed a pH<7.35 and 5 patients (33.3%) developed marked
      acidosis with base excess <-4.0 at the end of surgery. Both mean sodium and
      chloride levels were also significantly higher compared to its baseline values
      respectively (142.6+/-2.4 versus 138+/-2.7 mmol/L, P<0.01 and 105.7+/-4.1 versus
      113.2+/-3.0 mmol/L (P<0.01). CONCLUSIONS: A balanced solution (Sterofundin(r)ISO)
      provided significantly better control over acid-base balance, sodium and chloride
      levels when used as intraoperative fluid maintenance and replacement during
      elective neurosurgery.

PMID- 25854457
TI  - [Safety of polyethylene glycol conjugated L-asparaginase in patients with acute
      lymphoblastic leukemia and T cell non-Hodgkin lymphoma].
AB  - OBJECTIVE: To evaluate the safety of polyethylene glycol conjugated L
      asparaginase (PEG-Asp) for patients with adult acute lymphoblastic leukemia (ALL)
      and T cell non-Hodgkin lymphoma (T-NHL). METHODS: A retrospective analysis was
      conducted on the clinical data of 101 young patients (<=40 years old) with ALL
      and T-NHL, diagnosed at Peking Union Medical College Hospital between January
      2012 and June 2014. RESULTS: A total of 480 doses of PEG-Asp were administered in
      44 cases with ALL and 57 patients with T-NHL. Only one patient (0.2%) experienced
      mild allergic reaction. Other grade 3 or 4 toxicities of non-hematologic effects
      included low level of fibrogen (6.4%), elevated ALT (4.4%), blood glucose (2.3%),
      and triglyceridemia (2.3%), decreased albumin (0.8%) and elevated amylase (0.2%).
      Furthermore, 5 cases (1.0%) developed venous thrombosis, 9 cases (1.9%)
      hemorrage, 1 patient (0.2%) non-necrosis pancretitis. CONCLUSION: The risk of
      allergic reaction incurred by PEG-Asp is very low. It can be used safely in ALL
      and T-NHL. Coagulation status should be monitored during the treatment.

PMID- 25854458
TI  - [Impact of recombinant human thrombopoietin (rhTPO) on short-term response of
      immunosuppressive therapy in patients with newly diagnosed acquired severe
      aplastic anemia].
AB  - OBJECTIVE: To evaluate the impact of recombinant human thrombopoietin (rhTPO) on
      short-term response of immunosuppressive therapy (IST) in patients with newly
      diagnosed acquired severe aplastic anemia (SAA). METHODS: The clinical data of
      forty adult acquired SAA patients, who treated with IST combined with rhTPO, were
      retrospective analyzed and the hematologic recovery were compared with patients
      by the IST alone during the same period. The factors affecting the short-term
      response were also analyzed. RESULTS: At 3 months after IST, both the total
      response rate and CR+GPR rate in rhTPO group were much higher than those in
      control group (75.0% vs 50.0%, P=0.022; and 17.5% vs 2.5%, P=0.025). At 6 months
      after IST, there was no difference of total hematologic response rate in rhTPO
      group and control group (77.5% vs 57.5%, P=0.058), while the CR+GPR rate was
      still higher in rhTPO group (45.0% vs 22.5%, P=0.033). The median time of
      platelet transfusion independence was much shorter in rhTPO group [33(0-90) vs
      53(0-75) d, P=0.019]. Patients in rhTPO group needed less platelets transfusion
      support. The median platelet count in rhTPO group was 29(4-95)*109/L at 3 months
      after IST, which was much higher than that in control group [29(4-95)*109/L,
      P=0.006]. There was no significant difference regarding overall survival between
      the two groups (100.0% vs 91.0%, P=0.276). CONCLUSION: rhTPO is effective in
      promoting platelet recovery and improving the hematopoietic response for SAA
      patients with IST.

PMID- 25854460
TI  - [JAK2 V617F mutation burden and its clinical implications in 415 patients with
      myeloproliferative neoplasm].
AB  - OBJECTIVE: To detect JAK2 V617F mutation burden and its clinical implications in
      patients with myeloproliferative neoplasm (MPN). METHODS: JAK2 V617F mutation
      burden were detected by using MGB Taqman probes and its clinical significance
      were retrospectively studied in 415 MPN patients. RESULTS: JAK2 V617F was found
      in 56.9% of all patients [83.5% in polycythemia vera (PV), 55.9% in essential
      thrombocythemia (ET), 41.9% in primary myelofibrosis (PMF) and 64.7% in MPN
      unclassifiable)]. The majority of patients carried heterozygous JAK2 V617F
      mutation and homozygote was found only in 12 cases (4 in PV, 4 in MPN-U, 2 in
      PMF, 1 in ET, and 1 in chronic neutrophilic leukemia). Most patients (68.8%) were
      lower mutation burden (mutation burden<50%), but PV had the highest burden, the
      moderate burden in PMF and the least in ET. The patient's age and WBC count were
      significantly correlated with higher mutation burden in PV. WBC count was
      significantly related to higher mutation burden in ET. WBC count, Hb level and
      the platelet count were significantly related to higher mutation burden in PMF.
      CONCLUSION: The mutation burden of JAK2 V617F from high to low was PV, ET and
      PMF. The majority of JAK2 V617F mutation was heterozygous. JAK2 V617F mutation
      burden was positively correlated with age, WBC, Hb and platelet counts.

PMID- 25854456
TI  - Synaptic NMDA receptor activity is coupled to the transcriptional control of the
      glutathione system.
AB  - How the brain's antioxidant defenses adapt to changing demand is incompletely
      understood. Here we show that synaptic activity is coupled, via the NMDA receptor
      (NMDAR), to control of the glutathione antioxidant system. This tunes antioxidant
      capacity to reflect the elevated needs of an active neuron, guards against future
      increased demand and maintains redox balance in the brain. This control is
      mediated via a programme of gene expression changes that boosts the synthesis,
      recycling and utilization of glutathione, facilitating ROS detoxification and
      preventing Puma-dependent neuronal apoptosis. Of particular importance to the
      developing brain is the direct NMDAR-dependent transcriptional control of
      glutathione biosynthesis, disruption of which can lead to degeneration. Notably,
      these activity-dependent cell-autonomous mechanisms were found to cooperate with
      non-cell-autonomous Nrf2-driven support from astrocytes to maintain neuronal GSH
      levels in the face of oxidative insults. Thus, developmental NMDAR hypofunction
      and glutathione system deficits, separately implicated in several
      neurodevelopmental disorders, are mechanistically linked. 

PMID- 25854459
TI  - [Efficacy of continuous low-dose cyclophosphamide and prednisone regimen in
      refractory multiple myeloma patients with severe heart failure].
AB  - OBJECTIVE: To observe treatment response, survival, safety and the improvement of
      ECOG in patients with refractory multiple myeloma (MM) with serious heart failure
      after the administration of continuous low-dose of cyclophosphamide combined with
      prednisone (CP). METHODS: From January 2005 to September 2013, a total of 75
      patients were treated by metronomic chemotherapy with continuous low-dose
      cyclophosphamide (50 mg/d) and prednisone (15 mg/d). RESULTS: Among the 75
      patients, 2 were lost for follow-up. In the 73 available patients, the overall
      response was 64.4%, including 2 patients (2.7%) with complete remission (CR), 4
      cases (5.5%) very good partial remission (VGPR), and 24 patients (32.9%) partial
      remission (PR). The median survival was 12 months (1-70 months) with a median
      onset time of 90 days (16-120) and a median progressive freedom survival of 12
      months (1-60). The level of B-type natriuretic peptide in responders declined
      significantly, as compared to no responders [(336.6 +/- 30.3) ng/L vs (906.4 +/-
      104.8) ng/L, P<0.01]. Common adverse events were as follows: 32 (43.8%) cases of
      bone marrow suppression, 26 (35.6%) cases of infection, 8 cases of dizzy as well
      as sleepiness (11.0%), 7(9.6%) cases of Cushing syndrome, 4 (5.5%) cases of
      secondary diabetes mellitus, and 3 (4.1%) cases of edema respectively.
      CONCLUSION: The metronomic chemotherapy of cyclophosphamide combined with
      prednisone had satisfactory impact on the treatment outcome, including the
      improvement of cardiac functions and physical capacities, better survival and
      safety in refractory MM with serious heart failure. It provides a novel regimen
      for such patients.

PMID- 25854461
TI  - [Prognostic evaluation of comorbidities in patients with myelodysplastic
      syndrome].
AB  - OBJECTIVE: To discuss the impact of comorbidities on the outcomes of patients
      with MDS. METHODS: The clinical characteristics of 676 MDS patients with detailed
      comorbidities evaluations was analyzed retrospectively. RESULTS: There were
      395/676 cases (58.4%) with comorbidities (group 1), 281/676 cases (41.6%) without
      (group 2). Significant differences were seen in the distribution of age (>= 60
      y), bone marrow blasts, abnormal karyotype, WHO 2008 subtypes and IPSS-R risk
      cohorts (P<0.05) between the two groups. While gender, HGB concentrations, WBC
      levels, platelet levels and serum ferritin were not significantly different
      (P>0.05). Independent prognostic significance of comorbidities was seen in both
      uni-variate and multi-variate analyses (P<0.001). According to MDS-specific
      comorbidity index (MDS-CI), the median survival were 32(1-153) months, 19(2-85)
      months and 13(1-37) months in the low-risk, intermediate-risk and high-risk
      cohorts respectively, while 96(1-166) months in cohorts without any
      comorbidities, of which significant differences were seen (P<0.001). The MDS-CI
      allowed further stratification in the IPSS-R low-risk, intermediate-risk and high
      risk cohorts (P<0.001). CONCLUSION: Comorbidities provides prognostic
      stratification independently of IPSS-R for MDS patients.

PMID- 25854462
TI  - [Study on the relationship of platelet specific-autoantibodies with therapeutic
      outcomes by dexamethasone in immune thrombocytopenia purpura].
AB  - OBJECTIVE: To investigate the different outcomes by dexamethasone in adults
      immune thrombocytopenia purpura (ITP) with different types of platelet specific
      autoantibodies. METHODS: A total of 185 ITP were enrolled, 61 males and 124
      females, with a median age of 42 (18-83) years, including 117 newly diagnosed, 35
      persistent, and 33 chronic cases. All the patients received the dexamethasone at
      an initial dose of 40 mg per day for 4 days and a low dose of 5-10 mg for 3-4
      weeks. The platelet specific-autoantibodies were identified by the modified
      monoclonal antibody-specific immobilization of platelet antigen (MAIPA) assay.
      RESULTS: Among the IgG positive patients, the response rates in anti-GPIIb/IIIa
      antibody, anti-GPIbalpha antibody, both antibody positive, and both antibody
      negative were 87.5%, 50.0%, 68.0%, and 72.3% (chi2=11.489, P<0.05), respectively.
      Among the IgM positive patients, the response rates in the four groups were
      82.1%, 71.4%, 61.9%, and 68.9% (chi2=2.719, P=0.437), respectively. Among the
      GPIbalpha antibody positive patients, the response rates in IgG alone, IgM alone,
      both positive, and both negative were 52.4%, 59.1%, 76.1%, and 77.9%
      (chi2=10.811, P<0.05), respectively. Among the GPIIb/IIIa antibody positive
      patients, the response rates in the four groups were 73.3%, 71.0%, 78.6%, and
      66.3% (chi2=1.374, P=0.719), respectively. CONCLUSION: ITP patients with
      GPIbalpha-IgG antibody have worse response to dexamethasone treatment.

PMID- 25854463
TI  - [Efficacy of high-dose dexamethasone plus low-dose rituximab as a second-line
      treatment in 65 patients with primary immune thrombocytopenia].
AB  - OBJECTIVE: To observe the efficacy of high-dose dexamethasone in combination with
      low-dose rituximab as a second-line treatment for patients with immune
      thrombocytopenia (ITP). METHODS: 65 patients with ITP, previously by conventional
      dose of glucocorticoids, received high-dose dexamethasone in combination with low
      dose rituximab (dexamethasone 40 mg/d for 4 days, rituximab 100 mg, d 7, 14, 21,
      28 intravenous infusion). Treatment response, regulatory T cells (Treg),
      cytokines levels and treatment-related adverse effects were observed. RESULTS:
      Total response rate 1 month after treatment was achieved in 81.5% (53/65) of
      patients, and complete response at 3,6 and 12 months was 72.3% (47/65),
      66.2%(43/65), 63.1%(41/65). The higher efficiency and complete response rate was
      achieved in preexisting glucocorticoid-dependent patients. For patients with
      complete response, Treg cells continued to show a high level state [(3.01 +/-
      0.95)% vs (1.69 +/- 0.35)%, P=0.032], cytokines of BAFF [(648.03 +/- 79.63) ng/L
      vs (972.35 +/- 93.64) ng/L, P=0.001], IL-2 [(2.84 +/- 0.32) ng/L vs (4.18 +/-
      0.46) ng/L, P=0.012], sCD40L[(4.55 +/- 0.66) ng/L vs (7.73 +/- 1.04) ng/L,
      P=0.006] significantly lower than that before treatment. The level of IL-10 was
      increased, but without significance compared with that before treatment
      (P=0.136). All patients completed the protocol with no serious adverse reactions.
      CONCLUSION: The data show high-dose dexamethasone in combination with low-dose
      rituximab still has a satisfactory outcomes for patients previously with
      conventional dose of glucocorticoid.

PMID- 25854465
TI  - [Acquired aplastic anemia developing myelodysplastic syndrome/acute myeloid
      leukemia: clinical analysis of nineteen patients and literatures review].
AB  - OBJECTIVE: To analyze the clinical features of clonal evolution of acquired
      aplastic anemia (AA) into myelodysplastic syndrome/acute myeloid leukemia (AML)
      and review of literatures. METHODS: AA developing MDS/AML patients between
      December 1994 and December 2011 enrolled into this study to analyze their
      clinical characteristics. RESULTS: During the median follow-up of 49(15-97)
      months, 19 patients evolved to MDS/AML, of whom 10, 8 and 1 were from VSAA, SAA
      and NSAA subgroups, respectively. The median G-CSF therapy was 270(29-510) days.
      There were monosomy 7 in 11(57.9%) of 19 patients with AA evolved to MDS/AML. The
      median AA evolved to MDS/AML was 33(11-88) months. The median MDS/AML
      transformation in responders (54.2 months) was significantly longer than of non
      responders (25.7 months, P<0.01). CONCLUSION: AA patients could evolved into
      MDS/AML concomitant with abnormal karotype and worse prognosis.

PMID- 25854464
TI  - [Comparison of outcomes of adult acute lymphoblastic leukemia patients underwent
      autologous and allogeneic hematopoietic stem cell transplantation].
AB  - OBJECTIVE: To compare the outcomes of adult patients with acute lymphoblastic
      leukemia (ALL) who underwent autologous hematopoietic stem cell transplantation
      (auto-HSCT) and allogeneic hematopoietic stem cell transplantation (allo-HSCT).
      METHODS: From Jan 2007 to Dec 2010, 106 adult ALL patients were retrospectively
      divided into two groups, 50 in auto-HSCT group and 56 in allo-HSCT group. Auto
      HSCT group included 21 patients with high-risk, 46 patients in CR1 and 4 cases in
      CR2. All the 50 patients had negative minimal residual disease (MRD) prior to
      HSCT. Allo-HSCT group included 44 patients with high risk, 51 patients in CR1 and
      5 cases in CR2, 15 patients with positive MRD before allo-HSCT. response,
      regulatory T cells (Treg), cytokines levels and treatment-related adverse effects
      were observed. RESULTS: Of the total 106 patients, 29 patients relapsed at a
      medium follow-up of 22.9(0.8-63.3) months. The 3-year cumulative relapse rate
      (RR) was (29.9+/-8.0) % in auto-HSCT group and (32.7+/-6.8) % in allo-HSCT group.
      There were no significant differences in RR and overall survival (OS) between
      auto-HSCT and allo-HSCT groups, even of stratified risk groups. In standard risk
      group, 3-year OS was (77.1+/-13.2) % in auto-HSCT group and (90.9+/-8.7) % in
      allo-HSCT group (P=0.739). In high-risk group, 3-year OS was (68.7+/-10.8) %
      after auto-HSCT and (45.2+/-8.5) % after allo-HSCT (P=0.094). CONCLUSION: Due to
      acceptable RR and OS, adult ALL patients with no MRD before HSCT showed favorable
      survival. Auto-HSCT may be a considerable choice for adult ALL patients with
      negative MRD when lacking of donors for allo-HSCT.

PMID- 25854466
TI  - [Generation and identification of P210(T315I-BCR/ABL) transgenic mice].
AB  - OBJECTIVE: To construct the P210(T315I-BCR/ABL) transgenic mice model. METHODS:
      The transgenic vector in which the P210(T315I-BCR/ABL) gene and eGFP gene was
      derived by APN/CD13 promoter was constructed and microinjected into the single
      cell fertilized eggs of C57 mice. Transgene integration was conformed by PCR
      genotyping and P210(T315I-BCR/ABL) expression levels was evaluated by RT-PCR. The
      CML phenotype was confirmed by blood routine examination, Wright's staining for
      peripheral blood and bone marrow smears, HE staining for organs of transgenic
      mice. RESULTS: Three transgenic mice lines with high expression of P210(T315I
      BCR/ABL) gene and eGFP gene was selected. Compared with the wild type mice, the
      levels of WBC, platelet and neutrophil granulocyte of transgenic mice began to
      increase gradually at 2 months, and increase to 23.9*109/L, 4 136*109/L, and
      74.6% respectively at 6 months. The remarkable hyperplasia of granulocytes was
      seen in the peripheral blood and bone marrow smears with splenomegaly infiltrated
      by leukemic cells. CONCLUSION: The P210(T315I-BCR/ABL) transgenic mice was
      constructed and provided a model to explore the mechanism of T315I CML and screen
      out the drug for T315 CML patient.

PMID- 25854467
TI  - [Comparison of 10 mg/m2 or 8 mg/m2 idarubicin plus cytarabine regimen as
      induction chemotherapy for adult patients with newly diagnosed acute myeloid
      leukemia].
AB  - OBJECTIVE: To compare the efficacy and toxicity of 10 mg/m2 or 8 mg/m2 idarubicin
      (Ida) combined with cytarabine (IA"3+7"regimen) as induction chemotherapy for
      adult patients with newly diagnosed acute myeloid leukemia (AML). METHODS: From
      June 2004 to October 2013, 335 adult AML (non acute promyelocytic leukemia)
      patients receiving the IA regimen as induction chemotherapy were enrolled,
      including 198 cases with 10 mg/m2 Ida and 137 cases with 8 mg/m2 Ida for 3 days.
      We compared the hematologic response, hematologic side effects and prognosis
      between the two regimens. RESULTS: Except for 4 early deaths, the complete
      remission (CR) rate after the first cycle of induction chemotherapy was 72.5%,
      10.0% partial remission (PR) and 82.5% overall remission (OR) rate. The CR and OR
      rates were higher in the 10 mg/m2 Ida group than the 8 mg/m2 Ida group (CR: 78.9%
      vs 63.5%, P=0.003; OR: 88.2% vs 75.4%, P=0.007). Multivariate analysis showed
      that female, HGB>=100 g/L, FLT3-ITD mutation negative and 10 mg/m2 Ida were
      favorable factors for CR. All patients presented cytopenias of grade IV. There
      was no differences on the recovery time of ANC>=0.5*109/L and PLT>=20*109/L after
      induction chemotherapy. Within a median follow-up of 14 (1-118) months, 98
      (29.3%) patients relapsed, 92 (27.5%) died. The disease-free survival (DFS) and
      overall survival (OS) at 3 years were 53.2% and 58.9%, respectively. DFS and OS
      at 3-year were 34.2% and 37.4% in the chemotherapy cohort, 74.5% and 81.2% in the
      transplant cohort. 10 mg/m2 Ida was an independent favorite factor for DFS
      (P=0.040) and OS (P=0.007). CONCLUSION: As compared to 8 mg/m2, 10 mg/m2 Ida
      significantly improved the CR, with the same extent of hematological side
      effects, and was an independent favorite factor for DFS and OS.

PMID- 25854468
TI  - [Effects of decitabine against acute T lymphoblastic leukemia cell line Molt4].
AB  - OBJECTIVE: To explore the effects and possible mechanisms of decitabine on Molt4
      in vitro. METHODS: Effects of decitabine on cells proliferation were detected by
      using CCK-8, the apoptosis by Annexin V-FITC, cell cycles by propidium iodide
      FACS. Discrepancy genes were screened by RNA-seq technique. The CpG methylation
      of lactoferrin (LTF) gene in Molt4 cells were identified by Bisulfite sequencing
      PCR (BSP). The expression of LTF mRNA in Molt4 by RT-PCR and LTF protein
      expression were analyzed by Western blot. RESULTS: Decitabine effectively
      inhibited proliferation and induced apoptosis for Molt4 cells by an time- and
      dose-dependent manners. Cell cycles were arrested at the G0/G1 phase. The
      promoter methylation degree of LTF gene in Molt4 cells was 72.3% before
      decitabine treatment and decreased to 45.0% after treatment with 0.50 MUmol/L
      decitabine for 72 h. After the reduction of methylation, expression of its mRNA
      and protein increased, meanwhile caspase 3 and caspase 9 protein expression
      levels increased. CONCLUSION: The demethylating drug decitabine can induce
      apoptosis, detain cell cycle at phase G0/G1, inhibit proliferation and up
      regulate LTF gene expression in Molt4 cells. LTF may become a new target for
      acute T lymphoblastic leukemia.

PMID- 25854469
TI  - [Efficacy and safety of generic imatinib mesylate capsules produced in China for
      newly diagnosed chronic myeloid leukemia in chronic phase patients].

PMID- 25854470
TI  - [Establishment of a graft-versus-host disease mouse model for haplo-identical
      bone marrow transplantation with busulfan and fludarabine conditioning regimen].

PMID- 25854471
TI  - [A case report of Niemann-Pick disease complicated with gastric cancer].

PMID- 25854472
TI  - [Sorafenib in combination with chemotherapy as induction therapy for FLT3-ITD
      positive acute myeloid leukemia:nine cases report and literatures review].

PMID- 25854473
TI  - [Clinical analysis of 11 hematological diseases patients with gram-positive
      bacterial infection treated with daptomycin].

PMID- 25854474
TI  - [Clinical characteristics of hepatitis E virus infection in patients with
      hematological malignancies].

PMID- 25854475
TI  - [Multiple myeloma post renal transplant: one case report and literature review].

PMID- 25854476
TI  - [Bortezomib in combination with dexamethasone in the treatment of multiple
      myeloma induced rhabdomyolysis: a case report].

PMID- 25854477
TI  - [Advances in differential diagnosis and treatment of thrombotic microangiopathy].

PMID- 25854478
TI  - [Research progress in tumorigenicity of human induced pluripotent stem cells].

PMID- 25854479
TI  - [Hotspot report of 56th American Society of Hematology Annual Meeting: Hodgkin
      lymphoma].

PMID- 25854480
TI  - Determination of a Viral Load Threshold To Distinguish Symptomatic versus
      Asymptomatic Rotavirus Infection in a High-Disease-Burden African Population.
AB  - We evaluated quantitative real-time PCR to establish the diagnosis of rotavirus
      gastroenteritis in a high-disease-burden population in Malawi using enzyme
      immunoassay as the gold standard diagnostic test. In 146 children with acute
      gastroenteritis and 65 asymptomatic children, we defined a cutoff point in the
      threshold cycle value (26.7) that predicts rotavirus-attributable gastroenteritis
      in this population. These data will inform the evaluation of direct and indirect
      rotavirus vaccine effects in Africa. 

PMID- 25854481
TI  - Evaluation of a Real-Time Reverse Transcription-PCR Assay for Detection of
      Enterovirus D68 in Clinical Samples from an Outbreak in New York State in 2014.
AB  - An outbreak of severe respiratory illness associated with enterovirus D68 (EV
      D68) infection was reported in mid-August 2014 in the United States. In this
      study, we evaluated the diagnostic utility of an EV-D68-specific real-time
      reverse transcription-PCR (rRT-PCR) that was recently developed by the Centers
      for Disease Control and Prevention in clinical samples. Nasopharyngeal (NP) swab
      specimens from patients in a recent outbreak of respiratory illness in the lower
      Hudson Valley, New York State, were collected and examined for the presence of
      human rhinovirus or enterovirus using the FilmArray Respiratory Panel (RP) assay.
      Samples positive by RP were assessed using EV-D68 rRT-PCR, and the data were
      compared to results from sequencing analysis of partial VP1 and 5' untranslated
      region (5'-UTR) sequences of the EV genome. A total of 285 RP-positive NP
      specimens (260 from the 2014 outbreak and 25 from 2013) were analyzed by rRT-PCR;
      EV-D68 was detected in 74 of 285 (26.0%) specimens examined. Data for comparisons
      between rRT-PCR and sequencing analysis were obtained from 194 NP specimens. EV
      D68 detection was confirmed by sequencing analysis in 71 of 74 positive and in 1
      of 120 randomly selected negative specimens by rRT-PCR. The EV-D68 rRT-PCR showed
      diagnostic sensitivity and specificity of 98.6% and 97.5%, respectively. Our data
      suggest that the EV-D68 rRT-PCR is a reliable assay for detection of EV-D68 in
      clinical samples and has a potential to be used as a tool for rapid diagnosis and
      outbreak investigation of EV-D68-associated infections in clinical and public
      health laboratories. 

PMID- 25854482
TI  - Severe ketoalkalosis as initial presentation of imported human rabies in France.
AB  - We report a patient with an unusual initial metabolic presentation of imported
      human rabies who became symptomatic within 2 weeks of returning from Mali to
      France. This is the single case of imported human rabies identified in France
      within the past 11 years and the first report of viral RNA in bronchial
      secretions. 

PMID- 25854483
TI  - Pseudomonas aeruginosa and Periodontal Pathogens in the Oral Cavity and Lungs of
      Cystic Fibrosis Patients: a Case-Control Study.
AB  - Cystic fibrosis (CF) is the most frequent lethal genetic disease in the Caucasian
      population. Lung destruction is the principal cause of death by chronic
      Pseudomonas aeruginosa colonization. There is a high prevalence of oropharyngeal
      anaerobic bacteria in sputum of CF patients. This study was carried out due to
      the lack of results comparing subgingival periodontal pathogenic bacteria between
      the oral cavity and lungs in patients with CF in relation with P. aeruginosa
      presence. Our first goal was to detect P. aeruginosa in oral and sputum samples
      by culture and molecular methods and to determine clonality of isolates. In
      addition, subgingival periodontal anaerobic bacteria were searched for in sputum.
      A cross-sectional pilot case-control study was conducted in the CF Reference
      Center in Roscoff, France. Ten CF patients with a DeltaF508 homozygous mutation
      (5 chronically colonized [CC] and 5 not colonized [NC]) were enrolled. P.
      aeruginosa was detected in saliva, sputum, and subgingival plaque samples by real
      time quantitative PCR (qPCR). Subsequently, periodontal bacteria were also
      detected and quantified in subgingival plaque and sputum samples by qPCR. In CC
      patients, P. aeruginosa was recovered in saliva and subgingival plaque samples.
      Sixteen P. aeruginosa strains were isolated in saliva and sputum from this group
      and compared by pulsed-field gel electrophoresis (PFGE). Subgingival periodontal
      anaerobic bacteria were found in sputum samples. A lower diversity of these
      species was recovered in the CC patients than in the NC patients. The presence of
      the same P. aeruginosa clonal types in saliva and sputum samples underlines that
      the oral cavity is a possible reservoir for lung infection. 

PMID- 25854484
TI  - Unexpected Diagnosis of Cerebral Toxoplasmosis by 16S and D2 Large-Subunit
      Ribosomal DNA PCR and Sequencing.
AB  - The protozoan parasite Toxoplasma gondii causes severe opportunistic infections.
      Here, we report an unexpected diagnosis of cerebral toxoplasmosis. T. gondii was
      diagnosed by 16S and D2 large-subunit (LSU) ribosomal DNA (rDNA) sequencing of a
      cerebral biopsy specimen and confirmed by T. gondii-specific PCR and
      immunohistochemistry. The patient was later diagnosed with HIV/AIDS. 

PMID- 25854485
TI  - PhyResSE: a Web Tool Delineating Mycobacterium tuberculosis Antibiotic Resistance
      and Lineage from Whole-Genome Sequencing Data.
AB  - Antibiotic-resistant tuberculosis poses a global threat, causing the deaths of
      hundreds of thousands of people annually. While whole-genome sequencing (WGS),
      with its unprecedented level of detail, promises to play an increasingly
      important role in diagnosis, data analysis is a daunting challenge. Here, we
      present a simple-to-use web service (free for academic use at
      http://phyresse.org). Delineating both lineage and resistance, it provides state
      of-the-art methodology to life scientists and physicians untrained in
      bioinformatics. It combines elaborate data processing and quality control, as
      befits human diagnostics, with a treasure trove of validated resistance data
      collected from well-characterized samples in-house and worldwide. 

PMID- 25854486
TI  - Using new oral anticoagulants in patients undergoing major orthopedic surgery.
AB  - Four new oral anticoagulants (NOAC), apixaban, rivaroxaban, edoxaban, and
      dabigatran, are now available in the USA; however, only apixaban and rivaroxaban
      are FDA approved for the prevention of venous thromboembolism following
      orthopedic surgery. Apixaban, rivaroxaban, and edoxaban's anticoagulant activity
      can be measured using a chromogenic anti-factor Xa assay but there is no widely
      available means of measuring dabigatran blood levels. None of the NOAC has an
      antidote. Dabigatran is 80% renally excreted, and patients with atrial
      fibrillation taking dabigatran for stroke prevention should stop the drug 4-5
      days prior to major orthopedic surgery. Apixaban, rivaroxaban, and edoxaban
      should be held for 48 h preoperatively in this setting.

PMID- 25854487
TI  - Cogan's syndrome and other ocular vasculitides.
AB  - The clinical presentation of Cogan's syndrome has been classified as typical and
      atypical. Like other forms of ocular vasculitis, Cogan's syndrome has been found
      to have autoimmune origins with antibodies against the cornea, inner ear, and
      endothelial antigens. Antineutrophil cytoplasmic antibody (ANCA) and rheumatoid
      factor (RF) have been associated with Cogan's syndrome as well as ocular
      involving vasculitides not as strongly associated with the audiovestibular
      manifestations such as granulomatosis with polyangiitis and rheumatoid arthritis.
      The mainstay of therapy has been corticosteroids although other methods have been
      described in recalcitrant disease and to prevent development of systemic
      sequelae. 

PMID- 25854488
TI  - Antinuclear antibody (ANA) testing in patients treated with biological DMARDs: is
      it useful?
AB  - The appearance of biologic agents for the treatment of diverse autoimmune
      diseases in particular rheumatoid arthritis at the end of the 1990s changed the
      treatment of these patients. With the introduction of new agents in the treatment
      of rheumatic diseases, we started to notice the presence of new and sometimes
      unexpected adverse events. It is well recognized that infections are the main
      concern with these types of treatments; however, the occurrence of autoimmune
      abnormalities is also seen and its gaining perhaps more attention as the use of
      these agents is increasing. The first clinical trials of anti-tumor necrosis
      factor-alpha (anti-TNFalpha) inhibitors showed an increase of antinuclear and
      anti-double-stranded deoxyribonucleic acid (dsDNA) antibodies in patients treated
      with these agents. In this paper, we review the frequency of these autoantibodies
      in patients treated with biologic agents, particularly anti-TNF-alpha inhibitors,
      and its correlation with autoimmune processes as well as the clinical relevance
      of such findings. 

PMID- 25854489
TI  - Patient reported outcomes in rheumatoid arthritis clinical trials.
AB  - Patient reported outcomes (PRO) are at the core of assessing RA treatment
      response with patient assessments of global health or disease activity, pain, and
      physical function included in the calculation of American College of Rheumatology
      (ACR) responses. Progress has been made in assessing PROs that include additional
      patient-valued aspects of disease in recent RA randomized clinical trials (RCTs),
      particularly fatigue. Importantly, the National Institute of Health (NIH)-
      Patient Reported Outcomes Measurement Information System (PROMIS) development of
      psychometrically advanced generic health measures that span the range of symptoms
      potentially affected in RA, with high precision across the entire range of a
      symptom are undergoing additional study in RA and other rheumatologic diseases to
      establish their construct validity, responsiveness, and clinically meaningful
      cutoffs. PRO measures that are currently used and widely available can provide
      important perspectives not captured in composite clinical response criteria with
      the potential of better informing treatment decisions in clinical practice.

PMID- 25854490
TI  - Difficult clinical situations in the antiphospholipid syndrome.
AB  - Antiphospholipid syndrome (APS) is characterized by antiphospholipid antibodies
      (aPL) associated with thrombosis and/or pregnancy morbidity. However, there is a
      range of other manifestations associated with APS, called non-criteria
      manifestations that add significant morbidity to this syndrome and, some of them,
      represent difficult clinical situations to deal with. Other issues such as
      refractory treatment also represent challenging situations poorly addressed in
      the literature. Therefore, the purpose of this article is to review the
      management of difficult clinical situations in APS and provide information to
      help the readers in their decision-making process. 

PMID- 25854491
TI  - Rheumatic manifestations of scurvy.
AB  - This paper reviews the rheumatological manifestations of scurvy, based on
      articles published in English from 1965 until October 2014, with a particular
      focus on rheumatological manifestations. Scurvy is a rare, uncommon disease in
      developed countries. Due to its clinical heterogeneity, the disease can easily
      mimic rheumatologic conditions leading to a delay in diagnosis and treatment. 

PMID- 25854494
TI  - The missing piece of the puzzle: neuroinformatics at the bench.

PMID- 25854493
TI  - Automatic Dendritic Length Quantification for High Throughput Screening of Mature
      Neurons.
AB  - High-throughput automated fluorescent imaging and screening are important for
      studying neuronal development, functions, and pathogenesis. An automatic approach
      of analyzing images acquired in automated fashion, and quantifying dendritic
      characteristics is critical for making such screens high-throughput. However,
      automatic and effective algorithms and tools, especially for the images of mature
      mammalian neurons with complex arbors, have been lacking. Here, we present
      algorithms and a tool for quantifying dendritic length that is fundamental for
      analyzing growth of neuronal network. We employ a divide-and-conquer framework
      that tackles the challenges of high-throughput images of neurons and enables the
      integration of multiple automatic algorithms. Within this framework, we developed
      algorithms that adapt to local properties to detect faint branches. We also
      developed a path search that can preserve the curvature change to accurately
      measure dendritic length with arbor branches and turns. In addition, we proposed
      an ensemble strategy of three estimation algorithms to further improve the
      overall efficacy. We tested our tool on images for cultured mouse hippocampal
      neurons immunostained with a dendritic marker for high-throughput screen. Results
      demonstrate the effectiveness of our proposed method when comparing the accuracy
      with previous methods. The software has been implemented as an ImageJ plugin and
      available for use.

PMID- 25854495
TI  - A core-shell nanohollow-gamma-Fe2O3@graphene hybrid prepared through the
      Kirkendall process as a high performance anode material for lithium ion
      batteries.
AB  - We synthesized a core-shell structure with graphene as the shell and nano-hollow
      gamma-Fe2O3 as the core through a Kirkendall process at room temperature. When
      this hybrid is used as an anode material for lithium-ion batteries, it exhibits a
      remarkable electrochemical performance: a high reversible capacity of 1095, 833,
      and 551 mA h g(-1) at the current rates of 0.1 C, 1 C, and 2 C, respectively.
      When evaluated at 10 C, the capacity can still reach 504 mA h g(-1). 

PMID- 25854492
TI  - Pediatric antiphospholipid syndrome.
AB  - Antiphospholipid syndrome (APS) is a multisystem autoimmune condition
      characterized by vascular thromboses associated with persistently positive
      antiphospholipid antibodies. There is currently a paucity of data (incidence,
      prevalence, thrombosis risk, and effective treatment) in pediatric APS. The
      purpose of this report is to review the current literature on APS in children and
      neonates, identify the gaps in current knowledge, and suggest avenues for studies
      to fill those gaps. 

PMID- 25854496
TI  - Anterior cruciate ligament reconstruction-rehabilitation research methodological
      quality: a systematic review with world region comparisons.
AB  - PURPOSE: A systematic review and world region comparison of combined ACL
      reconstruction-rehabilitation studies was performed. METHODS: Studies that
      combined ACL surgical-rehabilitative management published between January 1990
      and June 2014 were evaluated. The combined terms "rehabilitation" and "anterior
      cruciate ligament reconstruction" or "ACL reconstruction" were used to search the
      CINAHL Plus, Cochrane Library, MEDLINE, PEDro, and PubMed databases. A total of
      5920 studies were initially identified. Inclusion criteria reduced this total to
      299 studies that underwent abstract review. Following this, 155 studies underwent
      full text review and 109 met all inclusion criteria for Modified Coleman
      Methodology Score (MCMS) evaluation. RESULTS: Overall, MCMS were 74.0 +/- 17
      (mean +/- standard deviation). Europe had slightly greater MCMS than North
      America (P = 0.041). Specific MCMS components that displayed significant world
      region differences included use of an independent investigator (Europe > North
      America and Asia; P = 0.047), including a patient-completed written assessment
      (Europe > North America and Asia; P = 0.009), allowing the patient to complete
      the assessment without medical, surgical, or rehabilitation personnel
      intervention (Europe > North America and Asia; P = 0.009), and use of well
      described subject selection or inclusion criteria (Europe > North America and
      Asia; P = 0.004). Tegner Activity Scale (P = 0.042) and VAS-Pain Scale (P =
      0.007) use was greater in Europe compared with other world regions. Primary
      rehabilitation theme frequency was comparable between world regions (n.s.).
      CONCLUSION: Regional research methodological quality differences were observed.
      Europe displayed a slightly greater MCMS for combined ACL reconstruction
      rehabilitation studies. With this information, research groups can design better
      team-based approaches to ensure that study findings provide sufficient
      significance to foster meaningful patient care improvements. LEVEL OF EVIDENCE:
      Systematic review, Level III.

PMID- 25854497
TI  - Alignment in knee flexion position during navigation-assisted total knee
      arthroplasty.
AB  - PURPOSE: The aim of this study was to demonstrate the lower limb alignment in
      knee flexion position after navigation-assisted total knee arthroplasty using the
      gap technique and to identify the correlative factors. METHODS: One hundred and
      twenty consecutive osteoarthritic knees (120 patients) were prospectively
      enrolled for intraoperative data collection. All TKA surgeries were performed
      using the navigation system (OrthoPilotTM, version 4.0; B. Braun Aesculap,
      Tuttlingen, Germany). Before and after final prosthesis implantation, the lower
      limb navigation alignment in both knee extension (0 degrees ) and knee flexion
      (90 degrees ) position was recorded. The knee flexion alignment was divided into
      three groups: varus, neutral and valgus alignment. To determine the factors of
      the alignment in knee flexion position, preoperative demographics, radiologic and
      intraoperative data were obtained. Pearson's correlation (r) analysis was
      performed to find the correlation. The Knee Society Score and Western Ontario and
      McMaster Universities Osteoarthritis Index were compared between groups. RESULTS:
      Although all postoperative extension alignment was within neutral position
      (between -2 degrees  and +2 degrees ), postoperative knee flexion alignment was
      divided into three groups: varus (<=-3 degrees ), 24 cases (20 %); neutral
      (between -2 degrees  and +2 degrees ), 85 cases (70.8 %) and valgus (>=+3 degrees
      ) alignment, 11 cases (9.2 %). There were a good correlation of alignment in knee
      flexion position with the rotation of femoral component relative to posterior
      condylar axis (r = -0.502, p = 0.000) and weak correlations with posterior
      femoral cut thickness (lateral condyle) (r = 0.207, p = 0.026), medial flexion
      (90 degrees ) gap after femoral component rotation adjustment (r = 0.276, p =
      0.003). Other variables did not show correlations. There were no statistical
      clinical differences between varus, neutral and valgus knee flexion alignment
      groups. CONCLUSION: About 30 % of the cases showed malalignment of more than 3
      degrees  in knee flexion position although with neutral alignment in extension
      position. The knee flexion alignment had a good correlation with the rotation of
      femoral component relative to posterior condylar axis. Neutral alignment in knee
      flexion position may be adjusted by femoral component rotation especially by the
      use of navigation system. LEVEL OF EVIDENCE: IV.

PMID- 25854498
TI  - Medial malleolar osteotomy for the treatment of talar osteochondral lesions:
      anatomical and morbidity considerations.
AB  - PURPOSE: Osteochondral lesions of the talus are often located posteromedially
      requiring open surgery to facilitate solid and complete osteochondral
      reconstruction. The aim of the study was to identify the optimal anatomical site
      for medial malleolar osteotomy based on the criteria of minimal cartilage damage
      (Study I) and to report on the morbidity in patients receiving osteotomy
      performed at the previously identified site (Study II). METHODS: For Study I,
      cartilage coverage of the tibiofibular ankle joint facet was measured in 40
      cadaveric ankles (20 cadaver specimens). In Study II, we assessed clinical (VAS
      pain score, AOFAS score, range of motion) and radiological outcome measures
      (SPECT-CT) in 17 patients (mean age, 36.8 +/- 10.8 years) undergoing medial
      malleolar osteotomy. RESULTS: The medial edge in the transition zone of the
      tibial plafond to the medial malleolus showed less than 75 % of cartilage
      coverage in 62.5 % of cadavers (Study I). Surgery resulted in lower pain levels
      (2.4 +/- 2.6 compared with 6.3 +/- 1.8 points; p < 0.001) and greater AOFAS
      scores (82.9 +/- 14.1 compared with 43.5 +/- 10.8 to points; p < 0.001) compared
      with baseline (Study II). No signs of intra-operative damage or mal- or non-union
      were found. Long-term morbidity was found in one patient. Implant removal was
      necessary in 12 of 17 patients (71 %). CONCLUSION: Anatomically, there is an
      optimal location for the medial malleolar osteotomy at the medial ankle edge
      involving minimal cartilage damage. Clinical results using this location showed
      no short- or mid-term morbidity and little long-term morbidity. However, many
      patients required re-intervention for implant removal. LEVEL OF EVIDENCE: IV.

PMID- 25854499
TI  - Early full weight-bearing versus 6-week partial weight-bearing after open wedge
      high tibial osteotomy leads to earlier improvement of the clinical results: a
      prospective, randomised evaluation.
AB  - PURPOSE: Open wedge high tibial osteotomy is a widespread treatment option in
      patients with varus malalignment and medial compartment osteoarthritis. There is
      no standardised protocol for post-operative rehabilitation available. The purpose
      of this study was to compare two post-operative rehabilitation protocols and to
      evaluate the clinical outcome of early full weight-bearing after open wedge HTO.
      METHODS: One hundred and twenty consecutive patients with varus malalignment and
      medial compartment osteoarthritis received an open wedge HTO using an angular
      locking plate fixation between December 2008 and December 2011. All patients were
      assigned randomly into one of two groups with different post-operative
      rehabilitation protocols (11-day vs. 6-week 20-kg partial weight-bearing).
      Clinical outcome was evaluated using established instruments (Lequesne, Lysholm,
      HSS and IKDC scores) preoperatively, 6, 12 and 18 months post-operatively.
      Deformity analysis was performed preoperatively and during follow-up. RESULTS:
      All clinical scores showed a significant pre- to post-operative improvement.
      After 6 months, there was a higher improvement in the group of early full weight
      bearing. The difference between preoperative and 6-month follow-up for the group
      with early full weight-bearing and for the group with 20-kg PWB for 6 weeks was
      28 +/- 26 and 18 +/- 22, respectively, for the Lysholm score and -5.0 +/- 5.1 and
      -3.0 +/- 3.6, respectively, for the Lequesne score. CONCLUSIONS: Early full
      weight-bearing (11-day 20-kg partial weight-bearing) after open wedge HTO without
      bone graft leads to earlier improvement of the clinical results and can be
      recommended for post-operative rehabilitation after open wedge HTO and fixation
      with an angular locking plate. LEVEL OF EVIDENCE: Therapeutic study, Level I.

PMID- 25854500
TI  - No difference in osteoarthritis after surgical and non-surgical treatment of ACL
      injured knees after 10 years.
AB  - PURPOSE: Aim of this study was to record and compare the functional and activity
      level as well as the manifestations of osteoarthritis after isolated ACL ruptures
      between patients with conservative treatment and ACL reconstruction with
      hamstrings tendon graft. METHODS: Thirty-two patients diagnosed with ACL rupture
      were recorded. Clinical examination included the Tegner and Lysholm activity
      scale, the International Knee Documentation Committee Subjective Form and KT-1000
      arthrometer. Narrowing of the medial and lateral joint spaces was assessed using
      the IKDC knee examination score. RESULTS: Median follow-up was 10.3 years (range
      10-11). Fifteen patients were conservatively treated (median age 33 years, range
      25-39). Seventeen patients were operated (median age 31 years, range 20-36).
      There was significant difference between the mean values of IKDC scores in favour
      of the ACL-reconstruction group of patients, 86.8 (SD 6.5) versus 77.5 (SD 13.8),
      respectively (p = 0.04). The mean value of anteroposterior tibial translation was
      1.5 mm (SD 0.2) for ACL-reconstruction group of patients, while the corresponding
      mean value for ACL-conservative group was 4.5 mm (SD 0.5), p = 0.03. Four
      patients in ACL-reconstruction group had radiological findings of grade C or D
      according to IKDC form. In ACL-conservative group, five patients presented
      similar signs (n.s.). CONCLUSIONS: ACL reconstruction using hamstrings autograft
      resulted in better functional outcome and laxity measurements than ACL
      conservative management. However, the incidence of radiological osteoarthritis
      was similar between the two groups and independent on the pre-operative grade of
      laxity and functional status of the patients. Equally, bone bruises were not
      found as a risk factor for the development of osteoarthritis after ACL rupture.
      LEVEL OF EVIDENCE: Prospective randomized study, Level II.

PMID- 25854501
TI  - Medial meniscal cyst as a cause of painful erosion of the tibial plateau.
AB  - Medial cysts are rarely encountered as a cause of bone erosion. It is thought
      meniscal cysts are present in up to 22 % of meniscal tear operations. MRI is the
      gold standard for visualisation of meniscal cysts. Decompression is often guided
      by careful study of the pre-operative MRI scans in multiple planes. This is the
      first case report demonstrating erosion of the medial tibial plateau due to an
      incarcerated meniscal cyst highlighting the potential for bone damage if left
      untreated. Level of evidence IV. 

PMID- 25854502
TI  - Robotic general surgery: current practice, evidence, and perspective.
AB  - BACKGROUND: Robotic technology commenced to be adopted for the field of general
      surgery in the 1990s. Since then, the da Vinci surgical system (Intuitive
      Surgical Inc, Sunnyvale, CA, USA) has remained by far the most commonly used
      system in this domain. The da Vinci surgical system is a master-slave machine
      that offers three-dimensional vision, articulated instruments with seven degrees
      of freedom, and additional software features such as motion scaling and tremor
      filtration. The specific design allows hand-eye alignment with intuitive control
      of the minimally invasive instruments. As such, robotic surgery appears
      technologically superior when compared with laparoscopy by overcoming some of the
      technical limitations that are imposed on the surgeon by the conventional
      approach. PURPOSE: This article reviews the current literature and the
      perspective of robotic general surgery. CONCLUSIONS: While robotics has been
      applied to a wide range of general surgery procedures, its precise role in this
      field remains a subject of further research. Until now, only limited clinical
      evidence that could establish the use of robotics as the gold standard for
      procedures of general surgery has been created. While surgical robotics is still
      in its infancy with multiple novel systems currently under development and
      clinical trials in progress, the opportunities for this technology appear
      endless, and robotics should have a lasting impact to the field of general
      surgery.

PMID- 25854503
TI  - Long-term results after in-situ split (ISS) liver resection.
AB  - PURPOSE: In-situ split (ISS) liver resection is a novel method to induce rapid
      hypertrophy of the contralateral liver lobe in patients at risk for postoperative
      liver failure due to insufficient liver remnant. So far, no data about
      oncological long-term survival after ISS liver resection is available. METHODS:
      We retrospectively analyzed our patients treated with ISS liver resection at the
      Department of Surgery of the University of Regensburg, the first center worldwide
      to perform ISS. RESULTS: Between 2007 and 2014, ISS liver resection was performed
      in 16 patients. Two patients (12.5 %) were lost in early postoperative phase (90
      days) and one was lost to follow-up. Thirteen patients with a follow-up period of
      more than 3 months were included into oncologically focused analyses. Median
      follow-up was 26.4 months (range 3.2-54.6). Seven patients had suffered from
      colorectal liver metastases (CRLM) and six from various other liver malignancies
      (non-CRLM). The ISS procedure had led to a median increase of 86.3 % of the left
      lateral liver lobe after a median of 9 days (range 4-28 days). Median disease
      free survival (DFS) was 14.6 months and median overall survival (OS) was 41.7
      months (26.4 months when including 90-days mortality). Three-year survival was
      calculated with 56.4 and 48.9 % when including perioperative mortality,
      respectively (CRLM 64.3 % vs. non-CRLM 50 %). CONCLUSION: ISS liver resection can
      provide long-term survival of selected patients with advanced liver malignancies
      that otherwise are not eligible for liver resection due to insufficient liver
      remnant.

PMID- 25854504
TI  - Euphorbia helioscopia Linn as a green source for synthesis of silver
      nanoparticles and their optical and catalytic properties.
AB  - During this study, we report the green synthesis of silver nanoparticles (Ag NPs)
      using Euphorbia helioscopia Linn leaf extract for the synthesis of
      propargylamines. Also, the structural and optical properties are studied. The
      synthesized nanoparticles are characterized by TEM, XRD, FT-IR and UV-visible
      techniques. UV-visible studies show an absorption band at 440 nm due to surface
      plasmon resonance (SPR) of the silver nanoparticles. Furthermore, the catalyst
      exhibits high catalytic activity, superior cycling stability and excellent
      substrate applicability.

PMID- 25854505
TI  - Enhancement photocatalytic activity of the graphite-like C3N4 coated hollow
      pencil-like ZnO.
AB  - The pencil-like ZnO hollow tubes with 9-12 MUm in length, 350-700 nm in width,
      200 nm in wall thickness coating with g-C3N4 have been prepared via a chemical
      deposition process. As compared with uncoated ZnO or g-C3N4, these g-C3N4/ZnO
      composites showed the enhanced photocatalytic activity which can be attributed to
      the heterojunction structure. Furthermore, it is worth pointing out that the
      weight ratios of g-C3N4 to ZnO (g-C3N4/ZnO) played a significantly influence on
      the photodegradable properties. With increasing the mass ratio, the
      photocatalytic activity increased firstly and then decreased after reaching to an
      optimal photocatalytic performance. It can be inferred that the appreciation of g
      C3N4 on the ZnO surface can improve the contact area which resulted in high
      separation of electrons and holes. However, excessive g-C3N4 may hinder the
      electrons transferring from the g-C3N4 to ZnO, and thus worse its photocatalytic
      performance. In our study, the g-C3N4/ZnO sample prepared with 10 wt% of g-C3N4
      exhibited the optimal photodegradable efficiency which 94% of Rhodamine B (RhB)
      has been degraded just in 2 h.

PMID- 25854506
TI  - Parts per billion detection of uranium with a porphyrinoid-containing
      nanoparticle and in vivo photoacoustic imaging.
AB  - Chemical tools that can report radioactive isotopes would be of interest to the
      defense community. Here we report ~250 nm polymeric nanoparticles containing
      porphyrinoid macrocycles with and without pre-complexed depleted uranium and
      demonstrate that the latter species may be detected easily and with high
      sensitivity via photoacoustic imaging. The porphyrinoid macrocycles used in the
      present study are non-aromatic in the absence of the uranyl cation, but aromatic
      after cation complexation. We solubilized both the freebase and metalated forms
      of the macrocycles in poly(lactic-co-glycolic acid) and found a peak in the
      photoacoustic spectrum at 910 nm excitation in the case of the uranyl complex.
      The signal was stable for at least 15 minutes and allowed detection of uranium
      concentrations down to 6.2 ppb (5.7 nM) in vitro and 0.57 ppm (19 fCi; 0.52 MUM)
      in vivo. To the best of our knowledge, this is the first report of a nanoparticle
      that detects an actinide cation via photoacoustic imaging. 

PMID- 25854507
TI  - First trimester dichorionic triplets: framing the choice.

PMID- 25854508
TI  - Evaluation of treatment response using integrated 18F-labeled choline positron
      emission tomography/magnetic resonance imaging in adolescents with intracranial
      non-germinomatous germ cell tumours.
AB  - The efficacy of hybrid 18F-Fluroethyl-Choline (FEC) positron emission tomography
      (PET)/magnetic resonance imaging (MRI) was investigated as an imaging modality
      for diagnosis and assessment of treatment response and remission status in four
      patients with proven or suspected intracranial non-germinomatous germ cell
      tumours (NGGCT). In two patients faint or absent choline avidity correlated with
      negative histology, whereas in other two patients, persistent choline avidity in
      the residual mass was suggestive of presence of viable tumour, subsequently
      confirmed histologically. We conclude that FEC-PET/MRI may be an effective
      imaging tool in detecting viable residual tumour in patients with intracranial
      NGGCT post treatment.

PMID- 25854509
TI  - Effect of sodium fluoride on male mouse fertility.
AB  - Sodium fluoride (NaF), an environmental pollutant, has been tested for its impact
      on fertility in several species of laboratory animals. A literature demonstrated
      that NaF adversely affects sperm motility, morphology, capacitation, and the
      acrosome reaction. However, the molecular mechanisms underlying these alterations
      have not yet been elucidated. Therefore, present study was designed to evaluate
      the regulatory pathways involved in the effect of NaF on sperm function and
      fertilization. In this in vitro study, mouse spermatozoa were incubated with a
      range of concentrations (2.5, 5, and 10 mm) of NaF for 90 min in media that
      support in vitro fertilization. Our results showed that NaF was associated with
      reduced intracellular ATP generation, motility, and motion kinematics. Likewise,
      short-term exposure of spermatozoa to NaF significantly reduced the intracellular
      calcium concentration, protein kinase-A activity, and tyrosine phosphorylation of
      sperm proteins, which were associated with a significant decrease in the rate of
      capacitation and the acrosome reaction. Finally, NaF significantly reduced the
      fertilization and blastocyst formation during early embryonic development. On the
      basis of these results, we propose that NaF reduces sperm motility, capacitation,
      and the acrosome reaction leading to poor fertilization and suppressed embryonic
      development.

PMID- 25854510
TI  - Repair of massive ventral hernias with "quilted" mesh.
AB  - INTRODUCTION: Prosthetic reinforcement is a critical component of hernia repair.
      For massive defects, mesh overlap is often limited by the dimensions of
      commercially available implants. In scenarios where larger mesh prosthetics are
      required for adequate reinforcement, it may be necessary to join several pieces
      of mesh together using non-absorbable suture. Here, we report our outcomes for
      abdominal wall reconstructions in which "quilted" mesh was utilized for fascial
      reinforcement. METHODS: Patients undergoing open incisional hernia repair
      utilizing posterior component separation and transversus abdominis muscle
      release, with use of quilted synthetic mesh placed in the retromuscular position,
      were reviewed. Main outcome measures included patient, hernia, and operative
      characteristics and post-operative outcomes, including surgical site occurrence
      (SSO), surgical site infection (SSI), and recurrence. RESULTS: Thirty-two
      patients (mean age 55.7 +/- 9.3, BMI 38.3 +/- 5.8 kg/m(2)) underwent open ventral
      hernia repair with "quilted" mesh placed in the retromuscular position. The mean
      defect area was 760.1 +/- 311.0 cm(2) with a mean width of 24.7 +/- 6.4 cm.
      Quilted meshes consisted of two-piece (69 %), three-piece (19 %) and four-piece
      (12 %) configurations. Wound morbidity consisted of eight (25 %) SSOs, including
      four (13 %) SSIs, all of which resolved without mesh excision. With mean follow
      up of 9.0 +/- 13.6 months, there were two (6.3 %) lateral recurrences, both
      unassociated with mesh-to-mesh suture line failure. CONCLUSIONS: Massive ventral
      hernias that require giant mesh prosthetics, currently not commercially
      available, may be successfully repaired using multiple mesh pieces sewn together
      in a quilt-like fashion. Such retromuscular repairs are durable, without added
      morbidity due to the mesh-to-mesh suture line. However, additional operative time
      is required for quilting the mesh together, prompting strong calls for
      manufacturing of larger mesh prosthetics.

PMID- 25854511
TI  - Feasibility of ASL spinal bone marrow perfusion imaging with optimized inversion
      time.
AB  - PURPOSE: To assess the correlation between flow-sensitive alternating inversion
      recovery (FAIR) and dynamic contrast-enhanced magnetic resonance imaging (DCE
      MRI) in the measurement of spinal bone marrow (SBM) perfusion; in addition, to
      assess for an optimized inversion time (TI) as well as the reproducibility of SBM
      FAIR perfusion. MATERIALS AND METHODS: The optimized TI of a FAIR SBM perfusion
      experiment was carried out on 14 volunteers; two adjacent vertebral bodies were
      selected from each volunteer to measure the change of signal intensity (DeltaM)
      and the signal-to-noise ratio (SNR) of FAIR perfusion MRI with five different
      TIs. Then, reproducibility of FAIR data from 10 volunteers was assessed by the
      reposition SBM FAIR experiments. Finally, FAIR and DCE-MRI were performed on 27
      subjects. The correlation between the blood flow on FAIR (BFASL ) and perfusion
      related parameters on DCE-MRI was evaluated. RESULTS: The maximum value of DeltaM
      and SNR were 36.39 +/- 12.53 and 2.38 +/- 0.97, respectively; both were obtained
      when TI was near 1200 msec. There were no significant difference between the two
      successive measurements of SBM BFASL perfusion (P = 0.879), and the within
      subject coefficients of variation (wCV) of the measurements was 3.28%. The BFASL
      showed a close correlation with K(trans) (P < 0.001) and Kep (P = 0.004), and no
      correlation with Ve (P = 0.082) was found. CONCLUSION: 1200 msec was the optimal
      TI for the SBM ASL perfusion image, which led to the maximum DeltaM and a good
      quality perfusion image. The SBM FAIR perfusion scan protocol has good
      reproducibility, and as blood flow measurement on FAIR is reliable and closely
      related with the parameters on DCE-MRI, FAIR is feasible for measuring SBM blood
      flow.

PMID- 25854512
TI  - A guide to the field of palaeo colour: Melanin and other pigments can fossilise:
      Reconstructing colour patterns from ancient organisms can give new insights to
      ecology and behaviour.
AB  - Melanin, and other pigments have recently been shown to preserve over geologic
      time scales, and are found in several different organisms. This opens up the
      possibility of inferring colours and colour patterns ranging from invertebrates
      to feathered dinosaurs and mammals. An emerging discipline is palaeo colour:
      colour plays an important role in display and camouflage as well as in
      integumental strengthening and protection, which makes possible the hitherto
      difficult task of doing inferences about past ecologies, behaviours, and
      organismal appearance. Several studies and techniques have been presented in the
      last couple of years that have described ways to characterize pigment patterns.
      Here, I will review the available methods and the likely applications to
      understand past ecologies. A golden age of colourized dinosaurs and other animals
      is now dawning upon us, which may elucidate the nature of ancient predator prey
      interactions and display structures.

PMID- 25854513
TI  - Single grain boundary break junction for suspended nanogap electrodes with
      gapwidth down to 1-2 nm by focused ion beam milling.
AB  - Single grain boundary junctions are used for the fabrication of suspended nanogap
      electrodes with a gapwidth down to 1-2 nm through the break of such junctions by
      focused ion beam (FIB) milling. With advantages of stability and no debris, such
      nanogap electrodes are suitable for single molecular electronic device
      construction. 

PMID- 25854514
TI  - Efficient co-delivery of a Pt(IV) prodrug and a p53 activator to enhance the
      anticancer activity of cisplatin.
AB  - A nanoplatform targeting DNA and p53 simultaneously is assembled. Layered double
      hydroxide nanoparticles are co-loaded with a Pt(IV) prodrug and a p53 activator.
      Once inside cells, cisplatin is released to attack genomic DNA and kill cancer
      cells; simultaneously, the p53 activator results in active p53, a key protein
      involved in the apoptotic pathways initiated by platinum drugs. The anticancer
      efficacy of cisplatin is significantly improved through this synergistic
      application.

PMID- 25854515
TI  - Giant mid-esophageal diverticula successfully treated by per-oral endoscopic
      myotomy.
AB  - BACKGROUND: Surgery is currently the preferred treatment choice for mid
      esophageal diverticula, while endoscopic therapy is rapidly establishing itself.
      METHOD: We report the first two cases of giant mid-esophageal diverticula
      presented with dysphagia successfully treated with per-oral endoscopic myotomy
      (POEM). RESULT: There were no complications during the procedure and the
      patients' conditions improved remarkably within short time of recovery.
      CONCLUSION: POEM could provide a safe, effective and less invasive treatment of
      mid-esophageal diverticula if appropriately used. Further studies on long-term
      efficacy with larger number of cases are necessary.

PMID- 25854516
TI  - Erratum to: Oncological and surgical results of laparoscopic versus open liver
      resection for HCC less than 5 cm: case-matched analysis.

PMID- 25854517
TI  - On causality and mechanisms in medical education research: an example of path
      analysis.
AB  - Studies in medical education can serve a variety of purposes. Studies that have a
      predominantly quantitative orientation may focus on estimating relations between
      variables, on estimating effects of one or more variables on some other
      variable(s), or on series of causal relations or mechanisms. Which is the focus
      of a particular study depends on the theoretical framework and research questions
      of that study. However, theory is of fundamental importance to medical education
      research, and studies focusing on series of causal relations or mechanisms can
      contribute greatly to the advancement of medical education research. This paper
      presents the potential benefits which result from adopting a path analysis
      perspective on the estimation of causal relations and conceptualization of
      mechanisms in medical education research. 

PMID- 25854518
TI  - Enlisting the power of the verb.

PMID- 25854519
TI  - Structure determination of bound nitrogen-based adducts with copper(II)
      acetylacetonato; an EPR, ENDOR and DFT study.
AB  - The adducts of bis(acetylacetonato)-copper(II), [Cu(acac)2], formed with a range
      of nitrogen heterocycles including pyridine (2), methylpyridines (3,4,5), amino
      methylpyridines (6,7) and diazines (8,9,10) were investigated in frozen solution
      using X-band EPR and 1H ENDOR spectroscopy. The small perturbations to the EPR
      spin Hamiltonian parameters (g and CuA) were consistent with the axial
      coordination of the nitrogen bases to Cu(II), and found to be dependent on both
      the basicity and steric influence of the coordinating substrate. The detailed
      structure of two adducts was then investigated by angular selective (1)H ENDOR
      and DFT. For the [Cu(acac)2](pyridine) adduct, axial coordination of the
      substrate was found to occur via the pyridine nitrogen as expected, producing a
      characteristic (1)H hyperfine coupling ((H)Ai = -2.6, -2.04, 4.7 MHz; beta = 36
      degrees ; aiso = 0.2 MHz) arising from the ortho-(1)H in the ring 2 or 6
      position. These results were confirmed by DFT. However, in the [Cu(acac)2](2
      amino-6-methyl-pyridine) adduct, the ENDOR data revealed a substantially
      different (1)H hyperfine coupling ((H)Ai = -4.52, -3.35, 6.47 MHz; beta = 14
      degrees ; aiso = -0.47 MHz) arising from the -NH2 amino protons. Analysis of this
      experimentally derived tensor in conjunction with the calculated DFT tensors,
      revealed that the 2-amino-6-methyl-pyridine substrate binds to Cu(II) via the
      exocyclic amino pyridine nitrogen, but with a tilt angle of 20 degrees  of the
      pyridine ring away from the geometry optimised structure. These results reveal
      how important structural information on the coordination geometry of Cu(II)
      adducts can be obtained by (1)H ENDOR, but only when the complete angular
      dependency profile of the ENDOR data is thoroughly considered.

PMID- 25854520
TI  - Ultrasound visualization of the lymphatic vessels in the lower leg.
AB  - BACKGROUND: Identification of lymphatic vessels for lymphaticovenular anastomosis
      (LVA), which is an effective surgical treatment for obstructive lymphedema, is
      important. Indocyanine green (ICG) lymphography is useful for that purpose, but
      is not common in many institutions. Although ultrasound is a very common
      modality, no research has yet underlined the feasibility of the device to detect
      the lymphatic vessels. METHODS: First, identification of lymphatic vessels in the
      lower legs using ultrasound was performed in non-edematous limbs with linear
      pattern on ICG lymphography (n = 12). The imaging findings and characteristic of
      the lymphatic vessels in ultrasonography were investigated on transverse scans.
      Second, to assess the ultrasound detection technique, ICG was injected to healthy
      volunteers after identification and marking of the lymphatic vessels using
      ultrasound (n = 14). Sensitivity and specificity of the examination were
      calculated. RESULTS: In the first part, the lymphatic vessels were detected by
      ultrasound in all cases. Characteristic ultrasonography findings of lymphatic
      vessels included homogeneous, hypoechoic and spicular misshapen images in all
      cases. In the second part, the overall sensitivity and specificity were 95.5 and
      92.9%, respectively. CONCLUSIONS: Ultrasonography can identify lymphatic vessels
      of the lower leg with precision and may aid lymphatic microsurgery for
      lymphedema. (c) 2015 Wiley Periodicals, Inc. Microsurgery 36:397-401, 2016.

PMID- 25854521
TI  - Simple (17) O NMR method for studying electron self-exchange reaction between UO2
      (2+) and U(4+) aqua ions in acidic solution.
AB  - (17) O NMR spectroscopy is proven to be suitable and convenient method for
      studying the electron exchange by following the decrease of (17) O-enrichment in
      U(17) OO(2+) ion in the presence of U(4+) ion in aqueous solution. The reactions
      have been performed at room temperature using I = 5 M ClO4 (-) ionic medium in
      acidic solutions in order to determine the kinetics of electron exchange between
      the U(4+) and UO2 (2+) aqua ions. The rate equation is given as R = a[H(+) ](-2) 
      + R', where R' is an acid independent parallel path. R' depends on the
      concentration of the uranium species according to the following empirical rate
      equation: R' = k1 [UO(2 +) ](1/2) [U(4 +) ](1/2)  + k2 [UO(2 +) ](3/2) [U(4 +)
      ](1/2) . The mechanism of the inverse H(+) concentration-dependent path is
      interpreted as equilibrium formation of reactive UO2 (+) species from UO2 (2+)
      and U(4+) aqua ions and its electron exchange with UO2 (2+) . The determined rate
      constant of this reaction path is in agreement with the rate constant of UO2 (2+)
      -UO2 (+) , one electron exchange step calculated by Marcus theory, match the
      range given experimentally of it in an early study. Our value lies in the same
      order of magnitude as the recently calculated ones by quantum chemical methods.
      The acid independent part is attributed to the formation of less hydrolyzed U(V)
      species, i.e. UO(3+) , which loses enrichment mainly by electron exchange with
      UO2 (2+) ions. One can also conclude that (17) O NMR spectroscopy, or in general
      NMR spectroscopy with careful kinetic analysis, is a powerful tool for studying
      isotope exchange reactions without the use of sophisticated separation processes.
      Copyright (c) 2015 John Wiley & Sons, Ltd. 

PMID- 25854522
TI  - Psychoeducation (brief) for people with serious mental illness.
AB  - BACKGROUND: Those with serious/severe mental illness, especially schizophrenia
      and schizophrenic-like disorders, often have little to no insight regarding the
      presence of their illness. Psychoeducation may be defined as the education of a
      person with a psychiatric disorder regarding the symptoms, treatments, and
      prognosis of that illness. Brief psychoeducation is a short period of
      psychoeducation; although what constitutes 'brief psychoeducation' can vary. A
      previous systematic review has shown that the median length of psychoeducation is
      around 12 weeks. In this current systematic review, we defined 'brief
      psychoeducation' as programmes of 10 sessions or less. OBJECTIVES: To assess the
      efficacy of brief psychoeducational interventions as a means of helping severely
      mentally ill people when added to 'standard' care, compared with the efficacy of
      standard care alone.The secondary objective is to investigate whether there is
      evidence that a particular kind (individual/ family/group) of brief
      psychoeducational intervention is superior to others. SEARCH METHODS: We searched
      the Cochrane Schizophrenia Group register September 2013 using the
      phrase:[*Psychoeducat* in interventions of STUDY]. Reference lists of included
      studies were also inspected for further relevant studies. We also contacted
      authors of included study for further information regarding further data or
      details of any unpublished trials. SELECTION CRITERIA: All relevant randomised
      controlled trials (RCTs) comparing brief psychoeducation with any other
      intervention for treatment of people with severe mental illness. If a trial was
      described as 'double blind' but implied randomisation, we entered such trials in
      a sensitivity analysis. DATA COLLECTION AND ANALYSIS: At least two review authors
      extracted data independently from included papers. We contacted authors of trials
      for additional and missing data. We calculated risk ratios (RR) and 95%
      confidence intervals (CI) of homogeneous dichotomous data. For continuous data,
      we calculated the mean difference (MD), again with 95% CIs. We used a fixed
      effect model for data synthesis, and also assessed data using a random-effects
      model in a sensitivity analysis. We assessed risk of bias for each included study
      and created 'Summary of findings' tables using GRADE (Grading of Recommendations
      Assessment, Development and Evaluation). MAIN RESULTS: We included twenty studies
      with a total number of 2337 participants in this review. Nineteen studies
      compared brief psychoeducation with routine care or conventional delivery of
      information. One study compared brief psychoeducation with cognitive behavior
      therapy.Participants receiving brief psychoeducation were less likely to be non
      compliant with medication than those receiving routine care in the short term (n
      = 448, 3 RCTs, RR 0.63 CI 0.41 to 0.96, moderate quality evidence) and medium
      term (n = 118, 1 RCT, RR 0.17 CI 0.05 to 0.54, low quality evidence).Compliance
      with follow-up was similar between the two groups in the short term (n = 30, 1
      RCT, RR 1.00, CI 0.24 to 4.18), medium term (n = 322, 4 RCTs, RR 0.74 CI 0.50 to
      1.09) and long term (n = 386, 2 RCTs, RR 1.19, CI 0.83 to 1.72).Relapse rates
      were significantly lower amongst participants receiving brief psychoeducation
      than those receiving routine care in the medium term (n = 406, RR 0.70 CI 0.52 to
      0.93, moderate quality evidence), but not in the long term.Data from a few
      individual studies supported that brief psychoeducation: i) can improve the long
      term global state (n = 59, 1 RCT, MD -6.70 CI -13.38 to -0.02, very low quality
      evidence); ii) promote improved mental state in short term (n = 60, 1 RCT, MD 
      2.70 CI -4.84 to -0.56,low quality evidence) and medium term; iii) can lower the
      incidence and severity of anxiety and depression.Social function such as
      rehabilitation status (n = 118, 1 RCT, MD -13.68 CI -14.85 to -12.51, low quality
      evidence) and social disability (n = 118, 1 RCT, MD -1.96 CI -2.09 to -1.83, low
      quality evidence) were also improved in the brief psychoeducation group. There
      was no difference found in quality of life as measured by GQOLI-74 in the short
      term (n = 62, 1 RCT, MD 0.63 CI -0.79 to 2.05, low quality evidence), nor the
      death rate in either groups (n = 154, 2 RCTs, RR 0.99, CI 0.15 to 6.65, low
      quality evidence). AUTHORS' CONCLUSIONS: Based on mainly low to very low quality
      evidence from a limited number of studies, brief psychoeducation of any form
      appears to reduce relapse in the medium term, and promote medication compliance
      in the short term. A brief psychoeducational approach could potentially be
      effective, but further large, high-quality studies are needed to either confirm
      or refute the use of this approach.

PMID- 25854523
TI  - Influence of substituents on cation-anion contacts in imidazolium perrhenates.
AB  - A series of imidazolium perrhenates with different substituents at the
      imidazolium ring were synthesised and characterised, including single crystal X
      ray diffraction. The effect of the substitution pattern on the state of
      aggregation of the compounds, the charge delocalisation and the ion pairing
      interaction via hydrogen bonds was studied. Particularly the substitution at the
      C2 position of the imidazolium ring was shown to be crucial to fine-tune the ion
      contacts. Fluorinated substituents appear to exhibit enhanced interionic
      interactions. The ability to tune the degree of contacts of the perrhenate anion
      allows for adjusting the nucleophilicity of this anion. 

PMID- 25854524
TI  - Patterns of use and patient characteristics: brachytherapy for localized prostate
      cancer in octo- and nonagenarians.
AB  - BACKGROUND: Brachytherapy (BT) is a widely used treatment modality for elderly
      patients with localized prostate cancer (PCa). OBJECTIVE: To describe the
      patterns of BT use in octo- and nonagenarians treated for localized PCa in the
      USA. We hypothesized that most individuals treated with BT should remain alive
      for at least 10 years. We also postulated that BT should ideally be administered
      as monotherapy. PATIENTS AND METHODS: Using the Surveillance Epidemiology and End
      Results (SEER)-Medicare-linked database, 2701 octo- and nonagenarians treated
      with BT between 1992 and 2009 were identified. Cumulative incidence rates and
      smoothed cumulative incidence plots were used. RESULTS: In patients with low-risk
      characteristics, 40 % received BT alone; 27 % received BT combined with ADT; 19 %
      received BT and EBRT; and 14 % received BT combined with both ADT and EBRT. Of
      intermediate-to-high-risk patients, 19 % received BT alone; 16 % received BT
      combined with ADT; 19 % received BT combined with EBRT; and 45 % received BT
      together with ADT and EBRT. Overall survival rate was 79 and 47 % at 5 and 10
      years. CONCLUSIONS: Less than half of elderly treated with BT remain alive at 10
      years of follow-up. Moreover, the vast majority of those individuals not only
      receives BT, but is also exposed to two or even three combined therapy
      modalities. These findings are worrisome.

PMID- 25854525
TI  - Austerity, sanctions, and the rise of food banks in the UK.

PMID- 25854526
TI  - A pilot study using carboplatin, vincristine, and temozolomide in children with
      progressive/symptomatic low-grade glioma: a Children's Oncology Group study?.
AB  - BACKGROUND: This study was initiated to test the feasibility and toxicity of a
      regimen that alternates the administration of weekly carboplatin and vincristine
      with temozolomide in the management of children with progressive and/or
      symptomatic low-grade glioma. METHODS: Eligible children received a 10-week
      induction regimen followed by six 10-week cycles of maintenance chemotherapy.
      Feasibility was evaluated with short-term and long-term endpoints. Short-term
      feasibility was evaluated by the ability to complete induction and 1 maintenance
      cycle in 24 weeks without >25% reduction in either carboplatin or temozolomide.
      Long-term feasibility was evaluated by the ability to administer induction and 4
      maintenance cycles within 60 weeks without >25% reduction in either carboplatin
      or temozolomide. Efficacy was assessed by response to initial chemotherapy and 5
      year event-free survival. Initial pathology was reviewed centrally. RESULTS:
      Sixty-six patients were enrolled on the study. It was feasible to deliver the
      regimen, and toxicity was acceptable. The only significant toxicities were
      hematologic. Both the short-term and long-term feasibility endpoints were met.
      The short-term feasibility success rate was 87% (95% CI: 77%-96%) and the long
      term feasibility success rate was 79% (95% CI: 68%-90%). The 5-year event-free
      survival was 46% (95% CI: 33%-58%) and the 5-year survival was 87% (95% CI: 75%
      93%). CONCLUSION: It was feasible to deliver the combination of weekly
      carboplatin and vincristine alternating with temozolomide to children with
      progressive/symptomatic low-grade glioma with acceptable toxicities. This
      combination appears to be effective in delaying progression. Further trials are
      needed to establish the relative efficacy of this regimen compared with other
      regimens in use.

PMID- 25854527
TI  - UDP-Glucuronosyltransferases 1A6 and 1A9 are the Major Isozymes Responsible for
      the 7-O-Glucuronidation of Esculetin and 4-Methylesculetin in Human Liver
      Microsomes.
AB  - Esculetin (6,7-dihydroxycoumarin, ET) and 4-methylesculetin (6,7-dihydroxy-4
      methylcoumarin, 4-ME) are typical coumarin derivatives that are attracting
      considerable attention because of their wide spectrum of biologic activities, but
      their metabolism remains unknown. This study aimed to elucidate the in vitro UDP
      glucuronosyltransferase (UGT) metabolism characteristics of ET and 4-ME. 7-O
      monoglucuronide esculetin (ET-G) and 7-O-monoglucuronide 4-methylesculetin (4-ME
      G) were identified by liquid chromatography-mass spectrometry (LC-MS) and (1)H
      nuclear magnetic resonance ((1)HNMR) when ET or 4-ME was incubated with human
      liver (HLM) in the presence of UDP-glucuronic acid. Screening assays with 12
      human expressed UGTs demonstrated that the formations of ET-G and 4-ME-G were
      almost exclusively catalyzed by UGT1A6 and UGT1A9. Phenylbutazone and carvacrol
      (UGT1A6 and UGT1A9 chemical inhibitors, respectively) at different concentrations
      (50, 100, and 200 MUM) significantly inhibited the formation of glucuronidates of
      ET and 4-ME in HLM, UGT1A6, and UGT1A9 when the concentrations of ET and 4-ME
      ranged from 10 to 300 MUM (P < 0.05). Clearance rates of ET in HLM, HIM, UGT1A6,
      and UGT1A9 were 0.54, 0.16, 0.69, and 0.14 ml/min/mg, respectively. Corresponding
      clearance rates values of 4-ME were 0.59, 0.03, 0.14, and 0.04 ml/min/mg,
      respectively. In conclusion, 7-O-monoglucuronidation by UGT1A6 and UGT1A9 was the
      predominant UGT metabolic pathway for both ET and 4-ME in vitro. The liver is
      probably the major contributor to the glucuronidation metabolism of ET and 4-ME.
      ET showed more rapid metabolism than 4-ME in glucuronidation. 

PMID- 25854528
TI  - Joint bleeds in von Willebrand disease patients have significant impact on
      quality of life and joint integrity: a cross-sectional study.
AB  - BACKGROUND: Joint bleeds (JB) are reported in a minority of patients with von
      Willebrand disease (VWD) but may lead to structural joint damage. Prevalence,
      severity and impact of JB in VWD are largely unknown. OBJECTIVES: The aim of this
      study was to assess JB prevalence, onset, treatment and impact on health-related
      quality of life (HR-QoL) and joint integrity in moderate and severe VWD. METHODS:
      In the Willebrand in the Netherlands study 804 moderate and severe VWD patients
      [von Willebrand factor (VWF) activity <=30U dL(-1)] completed a questionnaire on
      occurrence, sites and consequences of JB. To analyse JB number, onset, treatment
      and impact on joint integrity we additionally performed a patient-control study
      on medical file data comparing patients with JB to age, gender, factor VIII
      (FVIII)- and VWF activity matched VWD patients without JB. RESULTS: Of all VWD
      patients 23% (184/804) self-reported JB. These 184 patients reported joint damage
      more often (54% vs. 18%, P < 0.001) and had lower HR-QoL (SF36, P < 0.05)
      compared to VWD patients not reporting JB. Of 55 patients with available JB data,
      65% had the first JB before age 16. These 55 patients used more clotting factor
      concentrate (CFC; median dose 43 vs. 0 IE FVIII kg(-1) year(-1) , P < 0.001),
      more often had X-ray joint damage (44% vs. 11%, P = 0.001] and chronic joint pain
      (44% vs. 18%, P = 0.008) compared to 55 control VWD patients without JB.
      CONCLUSION: In conclusion, joint bleeds are reported by 23% of moderate and
      severe VWD patients, mostly start in childhood, are associated with more CFC use,
      joint pain, lower HR-QoL and significantly more radiological and self-reported
      joint damage.

PMID- 25854529
TI  - The effect of nutrient fortification of sauces on product stability, sensory
      properties, and subsequent liking by older adults.
AB  - There are potential nutritional and sensory benefits of adding sauces to hospital
      meals. The aim of this study was to develop nutrient fortified sauces with
      acceptable sensory properties suitable for older people at risk of
      undernutrition. Tomato, gravy, and white sauce were fortified with macro- and
      micronutrients using food ingredients rich in energy and protein as well as
      vitamin and mineral premixes. Sensory profile was assessed by a trained panel.
      Hedonic liking of fortified compared with standard sauces was evaluated by
      healthy older volunteers. The fortified sauces had higher nutritional value than
      the conventional ones, for example the energy content of the fortified tomato,
      white sauce, and gravy formulations were increased between 2.5- and 4-fold
      compared to their control formulations. Healthy older consumers preferred the
      fortified tomato sauce compared with unfortified. There were no significant
      differences in liking between the fortified and standard option for gravy. There
      were limitations in the extent of fortification with protein, potassium, and
      magnesium, as excessive inclusion resulted in bitterness, undesired flavors, or
      textural issues. This was particularly marked in the white sauce to the extent
      that their sensory characteristics were not sufficiently optimized for hedonic
      testing. It is proposed that the development of fortified sauces is a simple
      approach to improving energy intake for hospitalized older people, both through
      the nutrient composition of the sauce itself and due to the benefits of
      increasing sensorial taste and lubrication in the mouth. 

PMID- 25854531
TI  - Are There Any Racial and Ethnic Differences in Response to Medicines in Japanese
      Patients?

PMID- 25854530
TI  - Resveratrol Partially Suppresses Inflammatory Events but Does not Affect Stroke
      Onset in Stroke-Prone Spontaneously Hypertensive Rats.
AB  - AIM: Resveratrol has been shown to mimic the beneficial effects of dietary
      restriction (DR). We previously reported that DR delays stroke onset and extends
      the lifespan in Stroke-Prone Spontaneously Hypertensive rats (SHRSP). Therefore,
      we examined whether resveratrol mimics DR and delays stroke onset in SHRSP.
      METHODS: Cerebrovascular endothelial cells (CVECs) from SHRSP were treated with
      resveratrol, and the inflammatory gene expression levels and NFkappaB protein
      levels were measured. In order to address the effects of resveratrol in vivo,
      SHRSP (male, 10 weeks of age) were fed an experimental diet containing several
      doses of resveratrol (0 - 0.05% (w/w)), after which we measured the plasma
      cytokine levels and examined the stroke onset and lifespan. RESULTS: Treatment
      with resveratrol (100 MUM, 24 hours) in CVECs from SHRSP significantly decreased
      the interleukin (IL)-1beta-induced monocyte chemoattractant protein-1 (MCP-1)
      mRNA expression levels and p50 and p65 protein levels in the nuclear fraction.
      When the SHRSP were fed a diet containing resveratrol for one week, the
      resveratrol treatment did not affect the plasma lipid and glucose levels, body
      weight or weight of each tissue. Resveratrol slightly, but not significantly,
      decreased the plasma levels of IL-1beta and MCP-1 compared with that observed in
      the control group. In addition, resveratrol decreased the IL-1beta and MCP-1 mRNA
      expression levels in the brain versus the control animals. However, no doses of
      resveratrol delayed stroke onset or extended the lifespan in SHRSP. CONCLUSIONS:
      In this study, resveratrol did not delay stroke onset in SHRSP, although it
      partially suppressed systemic and cerebral inflammation. These results suggest
      that resveratrol does not mimic the beneficial effects of DR on stroke in vivo.

PMID- 25854532
TI  - Romiplostim mitigates dose-limiting thrombocytopenia of erucic acid for
      adrenomyeloneuropathy.

PMID- 25854533
TI  - Articular cartilage of the knee 3 years after ACL reconstruction. A quantitative
      T2 relaxometry analysis of 10 knees.
AB  - BACKGROUND AND PURPOSE: T1rho or T2 relaxation imaging has been increasingly used
      to evaluate the cartilage of the knee. We investigated the cartilage of ACL
      reconstructed knees 3 years after surgery using T2 relaxation times. PATIENTS AND
      METHODS: 10 patients with a clinically successful unilateral ACL reconstruction
      were examined 3 years after surgery. Multiple-TE fast-spin echo sagittal images
      of both knees were acquired using a 3T MRI scanner for T2 mapping of the
      tibiofemoral cartilage. T2 values of the superficial and deep zones of the
      tibiofemoral cartilage were analyzed in sub-compartmental areas and compared
      between the ACL-reconstructed and uninjured contralateral knees. RESULTS: Higher
      T2 values were observed in 1 or more sub-compartmental areas of each ACL
      reconstructed knee compared to the uninjured contralateral side. Most of the T2
      increases were observed at the superficial zones of the cartilage, especially at
      the medial compartment. At the medial compartment of the ACL-reconstructed knee,
      the T2 values of the femoral and tibial cartilage were increased by 3-81%
      compared to the uninjured contralateral side, at the superficial zones of the
      weight-bearing areas. T2 values in the superficial zone of the central medial
      femoral condyle differed between the 2 groups (p = 0.002). INTERPRETATION: The
      articular cartilage of ACL-reconstructed knees, although clinically satisfactory,
      had higher T2 values in the superficial zone of the central medial femoral
      condyle than in the uninjured contralateral side 3 years after surgery. Further
      studies are warranted to determine whether these patients would undergo cartilage
      degeneration over time.

PMID- 25854534
TI  - "She makes me feel that I'm not alone": linkage to Care Specialists provide
      social support to people living with HIV.
AB  - Wisconsin's Linkage to Care intervention incorporates elements of individually
      tailored patient navigation and case management designed to increase linkage and
      retention in HIV-related medical care. It is delivered by Linkage to Care
      Specialists in HIV medical clinics and community-based agencies. Researchers
      interviewed a diverse sample of clients to conduct preliminary evaluation of the
      pilot phase of this intervention. The participants' relationships with their
      Specialists emerged as a major unifying theme of the data. Comfortable and close
      relationships with Specialists served as motivation to adhere to medical care,
      mitigated negative feelings associated with HIV-related stigma, and resulted in
      increased comfort with medical care and positive health outcomes including
      engagement in care and undetectable viral load. As a result of the Specialists'
      support, many participants were reluctant to transition out of the Linkage to
      Care program. The positive effects demonstrated by Specialists are balanced
      against the costs of small caseloads that are potentially not feasible within
      traditional case management models. Future interventions to increase medical care
      engagement, among HIV+ individuals at risk of lack of engagement, should develop
      strategies to "personalize" the patient experiences within health care and
      psychosocial services delivery systems, as well as screening tools to triage
      clients into different levels of personal service provision intensity based on
      need and desire. 

PMID- 25854535
TI  - Effects of two physical education programmes on health- and skill-related
      physical fitness of Albanian children.
AB  - This study aims to evaluate the effectiveness of two school-based physical
      education (PE) programmes (exercise-based and games-based) compared with
      traditional PE, on health- and skill-related physical fitness components in
      children in Tirana, Albania. Participants were 378 first-grade (6.8 years) and
      389 fourth-grade (9.8 years) children attending four randomly selected schools in
      Tirana. Twenty-four school classes within these schools were randomly selected
      (stratified by school and school grade) to participate as exercise group (EG),
      games group (GG) and control group (CG). Both EG and GG intervention programmes
      were taught by professional PE teachers using station/circuit teaching framework
      while CG referred to traditional PE school lessons by a general teacher. All
      programmes ran in parallel and lasted 5 months, having the same frequency (twice
      weekly) and duration (45 min). Heart rate (HR) monitoring showed that intensity
      during PE lessons was significantly higher in the intervention groups compared
      with control (P < 0.001). Both PE exercise- and games programmes significantly
      improved several health- and skill-related fitness indicators compared with
      traditional PE lessons (e.g. gross motor skill summary score: 9.4 (95% CI 7.9;
      10.9) for exercise vs. control and 6.5 (95% CI 5.1; 8.1) for games vs. control,
      cardiorespiratory fitness: 2.0 ml O2 . min(-1) . kg(-1) (95% CI 1.5; 2.4) for
      exercise vs. control and 1.4 ml O2 . min(-1) . kg(-1) (95% CI 1.0; 1.8) for games
      vs. control). Furthermore, compared to games-based PE, exercise-based PE showed
      more positive changes in some gross motor coordination skills outcomes,
      coordination skills outcomes and cardiorespiratory fitness. The results from this
      study show that exercise- and games-based PE represents a useful strategy for
      improving health- and skill-related physical fitness in Albanian elementary
      school children. In addition, the study shows that exercise-based PE was more
      effective than games-based PE in improving gross motor function and
      cardiorespiratory fitness.

PMID- 25854536
TI  - Simultaneous chylothorax and chylous ascites in a patient with castration
      resistant prostate cancer after docetaxel chemotherapy: An unusual manifestation.

PMID- 25854537
TI  - TALOS: a multicenter, randomized, double-blind, placebo-controlled trial to test
      the effects of citalopram in patients with acute stroke.
AB  - RATIONALE: Selective Serotonin Reuptake Inhibitors (SSRI) are effective in the
      treatment of post-stroke depression and may have potential neuroprotective and
      vascular effects. Data from registry studies have further indicated a protective
      effect against recurrent ischemic events, but also an increased risk of bleeding
      in patients with ischemic stroke. Therefore, prospective studies are needed to
      determine the effects of SSRI treatment after acute ischemic stroke. AIMS AND
      DESIGN: TALOS is an investigator-initiated, national multicenter randomized- and
      placebo-controlled, double-blind trial testing citalopram in acute ischemic
      stroke. We hypothesize that citalopram treatment initiated in the acute phase
      after ischemic stroke will improve outcome assessed by the modified Rankin Score
      (mRS) and reduce the risk of death from vascular causes, transient ischemic
      attack (TIA)/stroke and myocardial infarction. STUDY OUTCOMES: There are two co
      primary effect variables: (i) Functional status at six-months, measured by the
      modified Rankin Scale, and (ii) Vascular death, TIA/stroke and myocardial
      infarction. Secondary effect variables include: (i) Single primary outcomes; (ii)
      The Barthel Index; (iii) Mini Mental State Examination at six-months; (iv) Final
      infarct size (Magnetic Resonance Imaging). DISCUSSION: SSRI treatment is well
      tolerated and overall beneficial in the wake of stroke; it may also be
      neuroprotective and prevent new vascular events.

PMID- 25854538
TI  - A simple genotyping procedure without DNA extraction to identify rare blood
      donors.
AB  - BACKGROUND: Transfusion-induced alloimmunization has severe clinical consequences
      including haemolytic transfusion reactions, impaired transfused RBCs longevity
      and greater difficulty in finding compatible blood. Molecular analysis of genomic
      DNA now permits prediction of blood group phenotypes based on identification of
      single nucleotide polymorphisms. Implementation of molecular technologies in
      donor centres would be helpful in finding RBC units for special patient
      populations, but DNA extraction remains an obstacle to donor genotyping.
      MATERIALS AND METHODS: We propose a simple method compatible with high throughput
      that allows blood group genotyping using a multiplex commercial kit without the
      need for DNA extraction. The principle relies on pre-PCR treatment of whole blood
      using heating/cooling procedure in association with a recombinant hotstart
      polymerase. RESULTS: In a prospective analysis, we yielded 5628 alleles
      identification and designated 63 donors with rare blood, that is either negative
      for a high-frequency antigen or with a rare combination of common antigens.
      CONCLUSION: The procedure was optimized for simplicity of use in genotyping
      platform and would allow not only to supply antigen-matched products to
      recipients but also to find rare phenotypes. This methodology could also be
      useful for establishing a donor repository for human platelet antigens (HPA)
      matched platelets since the same issues are involved for patients with neonatal
      alloimmune thrombocytopenia or post-transfusion purpura.

PMID- 25854539
TI  - Doubly-robust dynamic treatment regimen estimation via weighted least squares.
AB  - Personalized medicine is a rapidly expanding area of health research wherein
      patient level information is used to inform their treatment. Dynamic treatment
      regimens (DTRs) are a means of formalizing the sequence of treatment decisions
      that characterize personalized management plans. Identifying the DTR which
      optimizes expected patient outcome is of obvious interest and numerous methods
      have been proposed for this purpose. We present a new approach which builds on
      two established methods: Q-learning and G-estimation, offering the doubly robust
      property of the latter but with ease of implementation much more akin to the
      former. We outline the underlying theory, provide simulation studies that
      demonstrate the double-robustness and efficiency properties of our approach, and
      illustrate its use on data from the Promotion of Breastfeeding Intervention
      Trial. 

PMID- 25854540
TI  - Cobalt catalysis involving pi components in organic synthesis.
AB  - Over the last three decades, transition-metal-catalyzed organic transformations
      have been shown to be extremely important in organic synthesis. However, most of
      the successful reactions are associated with noble metals, which are generally
      toxic, expensive, and less abundant. Therefore, we have focused on catalysis
      using the abundant first-row transition metals, specifically cobalt. In this
      Account, we demonstrate the potential of cobalt catalysis in organic synthesis as
      revealed by our research. We have developed many useful catalytic systems using
      cobalt complexes. Overall, they can be classified into several broad types of
      reactions, specifically [2 + 2 + 2] and [2 + 2] cycloadditions; enyne reductive
      coupling; reductive [3 + 2] cycloaddition of alkynes/allenes with enones;
      reductive coupling of alkyl iodides with alkenes; addition of organoboronic acids
      to alkynes, alkenes, or aldehydes; carbocyclization of o-iodoaryl
      ketones/aldehydes with alkynes/electron-deficient alkenes; coupling of thiols
      with aryl and alkyl halides; enyne coupling; and C-H bond activation. Reactions
      relying on pi components, specifically cycloaddition, reductive coupling, and
      enyne coupling, mostly afford products with excellent stereo- and
      regioselectivity and superior atom economy. We believe that these cobalt
      catalyzed pi-component coupling reactions proceed through five-membered
      cobaltacyclic intermediates formed by the oxidative cyclometalation of two
      coordinated pi bonds of the substrates to the low-valent cobalt species. The high
      regio- and stereoselectivity of these reactions are achieved as a result of the
      electronic and steric effects of the pi components. Mostly, electron-withdrawing
      groups and bulkier groups attached to the pi bonds prefer to be placed near the
      cobalt center of the cobaltacycle. Most of these transformations proceed through
      low-valent cobalt complexes, which are conveniently generated in situ from air
      stable Co(II) salts by Zn- or Mn-mediated reduction. Overall, we have shown these
      reactions to be excellent substitutes for less desirable noble-metal systems.
      Recent successes in cobalt-catalyzed C-H activation have especially advanced the
      applicability of cobalt in this field. In addition to the more common low-valent
      cobalt-catalyzed C-H activation reactions, an in situ-formed cobalt(III) five
      membered complex with a 1,6-enyne effectively couples with aromatic ketones and
      esters through ortho C-H activation, opening a new window in this research area.
      Interestingly, this reaction proceeds under milder reaction conditions with broad
      substrate scope. Furthermore, many of the reactions we have developed are highly
      enantioselective, including enantioselective reductive coupling of enones and
      alkynes, addition of organoboronic acids to aldehydes, and the cyclization of 2
      iodobenzoates with aldehydes. Overall, this Account demonstrates the versatility
      and utility of cobalt catalysis in organic synthesis. 

PMID- 25854541
TI  - Relationship between vascular function indexes, renal arteriolosclerosis, and
      renal clinical outcomes in chronic kidney disease.
AB  - AIM: Hypertension contributes critically to the development of renal
      arteriolosclerosis in chronic kidney disease (CKD), but the impact of vascular
      function indexes including central blood pressure on renal arteriolosclerosis has
      not been investigated. We determined whether vascular function indexes were
      related to renal arteriolosclerosis and renal clinical outcomes in CKD. METHODS:
      This cross-sectional study was implemented in our hospital. Subjects were in
      patients with CKD aged >=20 years who underwent a renal biopsy. Vascular function
      indexes included central systolic blood pressure (SBP), cardio-ankle vascular
      index (CAVI), and renal resistive index. Central SBP was measured non-invasively
      using an automated device. Arteriolosclerosis was assessed histologically. Renal
      clinical outcomes included estimated glomerular filtration rate using serum
      creatinine (eGFRcreat) or cystatin C (eGFRcys), and the urinary albumin
      creatinine ratio. RESULTS: Among vascular function indexes, central SBP was
      weakly correlated with renal arteriolosclerosis (n = 55). Renal
      arteriolosclerosis was increased in hypertensive or hyperuricaemic patients, and
      negatively correlated with serum high-density lipoprotein (HDL) cholesterol and
      eGFRcys, which were independent risk factors for renal arteriolosclerosis in a
      stepwise multivariate regression analysis. Of the vascular function indexes, CAVI
      showed the strongest correlation with all renal clinical outcomes. Central SBP
      was correlated with only urinary albumin-creatinine ratio, while renal resistive
      index was correlated with eGFRcreat and urinary albumin-creatinine ratio.
      CONCLUSION: Decreased serum HDL cholesterol was independently and most closely
      associated with renal arteriolosclerosis. Of the vascular function indexes, CAVI
      had the greatest impact on renal clinical outcomes, although it was not
      associated with renal arteriolosclerosis.

PMID- 25854542
TI  - MicroRNA-494 promotes cyclosporine-induced nephrotoxicity and epithelial to
      mesenchymal transition by inhibiting PTEN.
AB  - A major complication associated with cyclosporine (CsA) treatment is
      nephrotoxicity. In this study, we examined whether microRNAs play a role in
      cyclosporine-induced nephrotoxicity. Treatment of mice with CsA resulted in
      nephrotoxicity that was associated with an early increase in expression of
      microRNA mmu-miR-494 (miR-494). Similarly, tubular epithelial cell epithelial
      mesenchymal transition (EMT) induced by CsA toxicity resulted in the upregulation
      of microRNA-494 and a decrease in PTEN levels in vitro. miR-494 directly targeted
      Pten and negatively regulated its expression. Preventing Pten targeting by miR
      494 was sufficient to prevent CsA induced EMT. Knockdown of miR-494 prevented the
      downregulation of PTEN in tubular epithelial cells following CsA treatment and
      also prevented CsA induced EMT. Thus, miR-494 plays a major role in promoting CsA
      induced nephrotoxicity through its ability to target Pten thereby contributing to
      EMT. We suggest that manipulating miR-494 expression may represent a novel
      approach to preventing EMT associated with CsA induced nephrotoxicity. 

PMID- 25854543
TI  - Perspectives on genetic and genomic technologies in an academic medical center:
      the duke experience.
AB  - In this age of personalized medicine, genetic and genomic testing is expected to
      become instrumental in health care delivery, but little is known about its actual
      implementation in clinical practice. METHODS: We surveyed Duke faculty and
      healthcare providers to examine the extent of genetic and genomic testing
      adoption. We assessed providers' use of genetic and genomic testing options and
      indications in clinical practice, providers' awareness of pharmacogenetic
      applications, and providers' opinions on returning research-generated genetic
      test results to participants. Most clinician respondents currently use family
      history routinely in their clinical practice, but only 18 percent of clinicians
      use pharmacogenetics. Only two respondents correctly identified the number of
      drug package inserts with pharmacogenetic indications. We also found strong
      support for the return of genetic research results to participants. Our results
      demonstrate that while Duke healthcare providers are enthusiastic about genomic
      technologies, use of genomic tools outside of research has been limited.
      Respondents favor return of research-based genetic results to participants, but
      clinicians lack knowledge about pharmacogenetic applications. We identified
      challenges faced by this institution when implementing genetic and genomic
      testing into patient care that should inform a policy and education agenda to
      improve provider support and clinician-researcher partnerships.

PMID- 25854544
TI  - Rice PCR1 influences grain weight and Zn accumulation in grains.
AB  - Proteins containing a placenta-specific 8 domain (PLAC8) function as major organ
      size regulators in Solanum lycopersicum and Zea may, and putative metal ion
      transporters in Arabidopsis thaliana, Oryza sativa and Brassica juncea. However,
      it is unknown how PLAC8 domain-containing proteins fulfill such diverse roles.
      Here, we found that plant cadmium resistance 1 (PCR1) influences both zinc (Zn)
      accumulation and grain weight in rice. OsPCR1 knockout and knockdown lines
      produced lighter grains than the wild type, while OsPCR1 overexpression lines
      produced heavier grains. Furthermore, the grains of OsPCR1 knockdown lines
      exhibited substantially higher Zn and lower cadmium (Cd) concentrations than the
      control, as did yeast heterologously expressing OsPCR1. Through sequence
      analysis, we showed that the amino acid sequence of japonica-type PCR1 was
      distinct from that of indica-type and wild rice accessions. This difference was
      correlated with distinct Zn-related phenotypes. Japonica-type PCR1 had a shorter
      N-terminus than did PCR1 in the other rice types, and yeast heterologously
      expressing japonica-type PCR1 was more sensitive to Zn than was yeast expressing
      indica-type PCR1. Furthermore, japonica-type grains accumulated less Zn than did
      indica-type grains. Our study suggests that rice PCR1 maintains metal ion
      homeostasis and grain weight and might have been selected for during
      domestication.

PMID- 25854545
TI  - Role of Peptide YY in blood vessel function and atherosclerosis in a rabbit
      model.
AB  - Cardiovascular disease remains a burden for Westernized countries. Peptide YY
      (PYY) raises blood pressure, yet its role has not yet been determined in diseased
      arteries. This study aimed at identifying PYY and eNOS in diseased blood vessels
      and to determine which blood vessels respond to PYY. New Zealand White rabbits
      were fed an atherogenic diet (n = 6, 0.5% cholesterol + 1% methionine + 5% peanut
      oil) and control animals fed a normal diet (n = 6) for 4 weeks.
      Immunohistochemistry was used to determine the localization of PYY and eNOS in
      the aorta. The aorta, carotid, renal, iliac, inferior mesenteric, and renal
      interlobular arteries were removed, mounted in organ baths, and subjected to
      doses of PYY (10(-9) -10(-7) mol/L) and then acetylcholine (10(-6) mol/L).
      Immunohistochemistry of the aorta shows PYY staining in plaque macrophages,
      smooth muscle cells and endothelium, and these cells co-expressed eNOS. PYY
      caused a minor vasoconstrictive response in all blood vessels studied but was
      blunted in arteries from control animals. Acetylcholine caused relaxation of PYY
      constricted blood vessels. This data clearly shows that PYY is present in
      atherosclerotic plaque and is a minor constrictor of the vasculature tree.
      Further studies aimed at understanding the role of PYY in cardiovascular disease
      are warranted.

PMID- 25854546
TI  - How to calculate the non-synonymous to synonymous rate ratio of protein-coding
      genes under the Fisher-Wright mutation-selection framework.
AB  - First principles of population genetics are used to obtain formulae relating the
      non-synonymous to synonymous substitution rate ratio to the selection
      coefficients acting at codon sites in protein-coding genes. Two theoretical cases
      are discussed and two examples from real data (a chloroplast gene and a virus
      polymerase) are given. The formulae give much insight into the dynamics of non
      synonymous substitutions and may inform the development of methods to detect
      adaptive evolution.

PMID- 25854547
TI  - Ultra-large scale AFM of lipid droplet arrays: investigating the ink transfer
      volume in dip pen nanolithography.
AB  - There are only few quantitative studies commenting on the writing process in dip
      pen nanolithography with lipids. Lipids are important carrier ink molecules for
      the delivery of bio-functional patters in bio-nanotechnology. In order to better
      understand and control the writing process, more information on the transfer of
      lipid material from the tip to the substrate is needed. The dependence of the
      transferred ink volume on the dwell time of the tip on the substrate was
      investigated by topography measurements with an atomic force microscope (AFM)
      that is characterized by an ultra-large scan range of 800 * 800 MUm(2). For this
      purpose arrays of dots of the phospholipid1,2-dioleoyl-sn-glycero-3
      phosphocholine were written onto planar glass substrates and the resulting
      pattern was imaged by large scan area AFM. Two writing regimes were identified,
      characterized of either a steady decline or a constant ink volume transfer per
      dot feature. For the steady state ink transfer, a linear relationship between the
      dwell time and the dot volume was determined, which is characterized by a flow
      rate of about 16 femtoliters per second. A dependence of the ink transport from
      the length of pauses before and in between writing the structures was observed
      and should be taken into account during pattern design when aiming at best
      writing homogeneity. The ultra-large scan range of the utilized AFM allowed for a
      simultaneous study of the entire preparation area of almost 1 mm(2), yielding
      good statistic results.

PMID- 25854548
TI  - Pulmonary Arteriovenous Malformations in Dyskeratosis Congenita.
AB  - Pulmonary arteriovenous malformations (PAVMs) are rare lesions known to cause
      cyanosis due to abnormal communication between the pulmonary arteries and veins.
      They are commonly seen in association with hereditary hemorrhagic telangiectasia,
      congenital heart disease, hepatopulmonary syndrome, and portopulmonary shunting,
      but rarely in patients with dyskeratosis congenita (DC). We describe a patient
      previously diagnosed with DC confirmed to have microscopic PAVMs after bone
      marrow transplantation and discuss possible pathogenic mechanisms. 

PMID- 25854549
TI  - Borealin dimerization mediates optimal CPC checkpoint function by enhancing
      localization to centromeres and kinetochores.
AB  - The chromosomal passenger complex (CPC) localizes to centromeres where it
      activates the mitotic checkpoint in response to inappropriate inter-kinetochore
      tension. This error correction function is essential for proper chromosome
      segregation. Here we define several critical features of CPC localization and
      function. First, the Borealin dimerization domain suppresses dynamic exchange at
      the centromere to allow optimal CPC function. Second, Borealin dimerization is
      essential to target a subpopulation of CPC proximal to the kinetochore when the
      mitotic spindle is disrupted. This subpopulation is also needed for full CPC
      checkpoint function. The existence of a pool of CPC at the kinetochore suggests
      that error correction is more complicated than predicted from the Aurora B
      phosphorylation gradient model. Finally, Haspin kinase plays a key role in
      maintaining the slowly exchanging centromere Borealin pool, while Aurora B and
      Mps1 play minimal roles in maintaining CPC localization once cells are in
      mitosis. 

PMID- 25854551
TI  - Post-abortion initiation of long-acting reversible contraception in New Zealand.
AB  - BACKGROUND: Post-abortion initiation of long-acting reversible contraception
      (LARC) reduces subsequent abortion rates within 24 months, but the prevalence of
      post-abortion LARC use in New Zealand is unknown. AIM: To describe post-abortion
      initiation of intrauterine and implantable LARC methods in New Zealand between
      2007 and 2012, and to determine what impact the introduction of government-funded
      (free) levonorgestrel (LNG) implants in August 2010 had on overall LARC use.
      DESIGN AND SETTING: Retrospective observational study involving New Zealand
      abortion clinic data. METHODS: Nationally collated data on post-abortion LARC
      insertions were obtained for the period 2007-2012, and individual-level discharge
      data for patients attending a large urban hospital abortion clinic were analysed
      using descriptive statistics to describe annual uptake rates, and the demographic
      profile of LARC users during this period. Logistic regression analyses examined
      whether LARC use differed by parity and/or age over time. RESULTS: Post-abortion
      LARC use increased from 20.2% in 2007 to 45.6% in 2012. Intrauterine device use
      increased from 20.2% to 31.8% during this period, with implants contributing a
      further 14% to the overall use of LARC methods by 2012. Clinic data showed that
      LARC use increased among most demographic subgroups between 2009 and 2012, with
      the greatest increase among nulliparous under-20-year-olds (from 17.2% to 42.0%).
      CONCLUSIONS: Post-abortion LARC use has been steadily increasing in New Zealand
      since 2007. Overall LARC use significantly increased following the introduction
      of government-funded implants, particularly among young and nulliparous women.
      Improving access to alternative methods of LARC may further increase uptake and
      reduce unwanted pregnancy rates.

PMID- 25854550
TI  - Intrauterine contraception in nulliparous women: a prospective survey.
AB  - BACKGROUND: Intrauterine contraception is a first-line option for young women,
      yet relatively few prospective studies have been performed in nulliparous women
      using currently available devices, and many providers are still reluctant to
      provide this option. METHODS: Between January 2012 and June 2014, 109 nulliparous
      women, aged 18-30 years, who had an intrauterine device (IUD) placed at a student
      health clinic [88 levonorgestrel-intrauterine system (LNG-IUS) users and 21 Cu T
      380A (IUD) users] were surveyed at 1, 6, 12 and 18 months after insertion.
      RESULTS: Overall satisfaction was high; at follow-up survey 83% of 100 women
      (mean use 13.4 months) were 'happy' or 'very happy' with their IUD, and there
      were no differences in satisfaction between the two IUD types. Some 75% of
      participants stated that the insertion procedure went 'very well', despite 78%
      rating insertion pain as moderate to severe, and 46% experiencing vasovagal
      symptoms. The 12-month continuation rate was 89%, with discontinuations for
      expulsion (3%), side effects (6%), lack of anticipated benefit (1%) and pregnancy
      (1%). Users of the Cu T 380A were more likely to have heavy menses (74% vs 2%;
      p<0.0001) or moderate to severe cramping (68% vs 20%; p=0.0002) compared with LNG
      IUS users. There were no uterine perforations or diagnoses of pelvic inflammatory
      disease. The rate of failed insertions during the study period was 6.2%.
      CONCLUSIONS: Despite significant symptoms with insertion, intrauterine
      contraception is safe, effective and ultimately well tolerated in nulliparous
      women and should be provided to this population in both university and community
      health settings.

PMID- 25854552
TI  - An investigation of herpes simplex virus type 1 latency in a novel mouse dorsal
      root ganglion model suggests a role for ICP34.5 in reactivation.
AB  - After a primary lytic infection at the epithelia, herpes simplex virus type 1
      (HSV-1) enters the innervating sensory neurons and translocates to the nucleus,
      where it establishes a quiescent latent infection. Periodically, the virus can
      reactivate and the progeny viruses spread back to the epithelium. Here, we
      introduce an embryonic mouse dorsal root ganglion (DRG) culture system, which can
      be used to study the mechanisms that control the establishment, maintenance and
      reactivation from latency. Use of acyclovir is not necessary in our model. We
      examined different phases of the HSV-1 life cycle in DRG neurons, and showed that
      WT HSV-1 could establish both lytic and latent form of infection in the cells.
      After reactivating stimulus, the WT viruses showed all markers of true
      reactivation. In addition, we showed that deletion of the gamma(1)34.5 gene
      rendered the virus incapable of reactivation, even though the virus was clearly
      able to replicate and persist in a quiescent form in the DRG neurons.

PMID- 25854553
TI  - Inhibition of HIV-1 infection of primary CD4+ T-cells by gene editing of CCR5
      using adenovirus-delivered CRISPR/Cas9.
AB  - CCR5 serves as an essential coreceptor for human immunodeficiency virus type 1
      (HIV-1) entry, and individuals with a CCR5(Delta32) variant appear to be healthy,
      making CCR5 an attractive target for control of HIV-1 infection. The CRISPR/Cas9,
      which functions as a naturally existing adaptive immune system in prokaryotes,
      has been recently harnessed as a novel nuclease system for genome editing in
      mammalian cells. Although CRISPR/Cas9 can be readily delivered into cell lines,
      due to the large size of the Cas9 protein, efficient delivery of CCR5-targeting
      CRISPR/Cas9 components into primary cells, including CD4(+) T-cells, the primary
      target for HIV-1 infection in vivo, remains a challenge. In the current study,
      following design of a panel of top-ranked single-guided RNAs (sgRNAs) targeting
      the ORF of CCR5, we demonstrate that CRISPR/Cas9 can efficiently mediate the
      editing of the CCR5 locus in cell lines, resulting in the knockout of CCR5
      expression on the cell surface. Next-generation sequencing revealed that various
      mutations were introduced around the predicted cleavage site of CCR5. For each of
      the three most effective sgRNAs that we analysed, no significant off-target
      effects were detected at the 15 top-scoring potential sites. More importantly, by
      constructing chimeric Ad5F35 adenoviruses carrying CRISPR/Cas9 components, we
      efficiently transduced primary CD4(+) T-lymphocytes and disrupted CCR5
      expression, and the positively transduced cells were conferred with HIV-1
      resistance. To our knowledge, this is the first study establishing HIV-1
      resistance in primary CD4(+) T-cells utilizing adenovirus-delivered CRISPR/Cas9.

PMID- 25854554
TI  - PET beyond 18F-FDG: second generation PET tracers in clinical oncology.

PMID- 25854555
TI  - Precise fusion of MRI and dual energy 111In WBC/99mTc HDP SPECT/CT in the
      diabetic foot using companion CT: an example of SPECT/MRI imaging.
AB  - AIM: The purpose of our study was to correctly fuse MRI and SPECT 111In WBC and
      99m Tc HDP images using companion CT images. The fused images could be used to
      assess proper surgical approach in treatment of the diabetic foot. METHODS: Nine
      patients who had dual energy 111In WBC/ 99m Tc HDP SPECT/CT and MRI studies
      within a week were investigated in an ongoing project. A GE Infinia SPECT/CT
      camera and Siemens MAGNETOM 1.5T MR system were used in this study. First, the
      MRI and corresponding CT images were coregistrated using a transformation based
      on normalized mutual information. The transformation was saved and used for MRI
      and 111In WBC/ 99m Tc HDP SPECT fusion. A Jaszczak phantom study was also
      performed in order to estimate accuracy of MRI/ SPECT fusion. RESULTS: The
      Jaszczak phantom study with 3.7 MBq 111In hot sphere showed that MRI/SPECT
      alignment using the approach described above produced registration with 0.7 +/-
      0.4 mm accuracy in all three dimensions (3D). The nine clinical cases were
      visually evaluated and showed 1-2 mm 3D fusion accuracy. MRI provides almost
      perfect anatomy of soft tissue and bony structures but it may exaggerate the
      extent of infection. 111In WBC/99m Tc HDP SPECT imaging is more accurate for
      infection detection but lacks anatomical reference. Combination of these images
      proved an essential adjunct to diagnosis. A clinical utility of the approach is
      illustrated in two clinical examples. CONCLUSION: The CT in dual energy 111In
      WBC/99m Tc HDP SPECT/CT studies can be used to accurately fuse and compare 111In
      WBC/99m Tc HDP SPECT and MRI images of the diabetic foot. This can significantly
      help in conservative treatment planning and limb salvage procedures in treatment
      of diabetic foot infections.

PMID- 25854556
TI  - Penetration of biomass-burning emissions from South Asia through the Himalayas:
      new insights from atmospheric organic acids.
AB  - High levels of carbonaceous aerosol exist over South Asia, the area adjacent to
      the Himalayas and Tibetan Plateau. Little is known about if they can be
      transported across the Himalayas, and as far inland as the Tibetan Plateau. As
      important constituents of aerosols, organic acids have been recognized as unique
      fingerprints to identify the atmospheric process. Here we measured dicarboxylic
      acids and related compounds in aerosols on the northern slope of Mt. Everest
      (Qomolangma, 4276 m a.s.l.). Strong positive correlations were observed for
      dicarboxylic acids with biomass burning tracers, levoglucosan and K(+),
      demonstrating that this area was evidently affected by biomass burning. The
      seasonal variation pattern of dicarboxylic acids is consistent with OC and EC,
      being characterized by a pronounced maximum in the pre-monsoon season. Molecular
      distributions of dicarboxylic acids and related compounds (malonic acid/succinic
      acid, maleic acid/fumaric acid) further support this finding. We suggest that the
      local meteorological conditions and regional atmospheric flow process could
      facilitate the penetration of the carbonaceous aerosols from South Asia
      throughout the Himalayas. With the consideration of the darkening force of
      carbonaceous aerosols, our finding has important implication for this climate
      sensitive area, where the glacier melting supplies water for billions of people
      downstream. 

PMID- 25854557
TI  - [Interleukin-37 inhibits the activation of mouse dendritic cells induced by
      lipopolysaccharides].
AB  - OBJECTIVE: To investigate the role of interleukin-37 (IL-37) in regulating the
      activation of mouse dendritic cells (DCs) induced by lipopolysaccharides (LPS).
      METHODS: The mouse bone marrow cells was induced to differentiate into DCs with
      GM-CSF and IL-4. DCs were purified with anti-CD11c immunomagnetic beads. After
      pretreated with IL-37, DCs were stimulated by LPS. Then the levels of co
      stimulatory molecules CD80 and CD86 on DCs were detected by flow cytometry. The
      mRNA levels of inflammation cytokines tumor necrosis factor alpha (TNF-alpha), IL
      6 and IL-1alpha were determined by real-time quantitative PCR. The protein levels
      of inflammatory cytokines IL-1alpha, IL-6, TNF-alpha were measured by cytometric
      beads array (CBA) kit. RESULTS: We induced successfully DCs and obtained a high
      purity of DCs (>90%) with anti-CD11c immunomagnetic beads. After stimulated by
      LPS, the levels of co-stimulating molecules CD80, CD86 on IL-37-treated DCs were
      reduced, and the expressions of the cytokines TNF-alpha, IL-6 and IL-1alpha were
      also down-regulated at both mRNA and protein levels. CONCLUSION: IL-37 plays a
      critical role in inhibiting LPS-induced DCs activation via suppressing production
      of co-stimulatory molecules CD80, CD86 and pro-inflammatory cytokines.

PMID- 25854558
TI  - [Low-dose lipopolysaccharide mediated up-regulation of Nrf2 attenuates
      inflammatory response in rats with spinal cord injury].
AB  - OBJECTIVE: To explore the neuroprotective effects of preconditioning with low
      dose lipopolysaccharide (LPS) in rats after spinal cord injury and its possible
      mechanism. METHODS: Forty-eight female SD rats were randomly divided into four
      groups as follows: empty virus (EV), LPS combined with empty virus (LPS-EV),
      nuclear factor erythroid 2-related factor 2 (Nrf2) interference virus (NIV), and
      LPS combined with Nrf2 interference virus (LPS-NIV) (n=12 per group). The model
      of traumatic spinal cord injury (TSCI) was established by the modified Allen's
      method. Hind limb motor function of the rats was assessed by the Basso, Beattie
      and Bresnahan (BBB) score 3 days after the operation. The injured spinal cord
      tissues were harvested after the operation. The pathological changes of spinal
      cord were observed by HE staining. The Nissl body and neuron survival index were
      assessed by Nissl staining. The expressions of Nrf2, NF-kappaB and associated pro
      inflammatory cytokines (IL-1beta, TNF-alpha) were detected by immunohistochemical
      staining and Western blotting. RESULTS: NIV group showed descended Nrf2 protein
      expression and ascended NF-kappaB, IL-1beta, TNF-alpha protein levels compared
      with EV group, and no significant difference from LPS-NIV group. The Nrf2 protein
      expression of LPS-EV group increased significantly compared with EV group and LPS
      NIV group, and NF-kappaB, TNF-alpha and IL-1beta protein expression decreased
      significantly at the same time. Compared with those of EV group and LPS-NIV
      group, the neuron survival index of LPS-EV group was improved. The morphological
      change of LPS-EV group was also obviously alleviated. The BBB score had no
      statistical significance among these groups. CONCLUSION: Low-dose LPS
      preconditioning had neuroprotective effects on spinal cord injury. This
      protective effect was mediated by activating the Nrf2 to down-regulate
      expressions of NF-kappaB and pro-inflammatory cytokines and alleviate
      inflammatory response.

PMID- 25854560
TI  - [Wnt3a combined with bone morphogenetic protein 9 induce C3H10T1/2 cells
      differentiation into cardiomyocyte-like cells in vitro].
AB  - OBJECTIVE: To investigate the effects of Wnt3a alone and combined with bone
      morphogenetic protein 9 (BMP9) on the differentiation of C3H10T1/2 cells into
      cardiomyocyte-like cells. METHODS: Recombinant adenovirus GFP, BMP9 and Wnt3a
      were amplified with human embryo kidney 293 cell line (HEK293 cells) and
      transferred into C3H10T1/2 cells. Three weeks after transfection, the cell
      morphology and the expression of green fluorescent protein in cells transfected
      with GFP, BMP9 and Wnt3a were observed by an inverted microscope and a
      fluorescence microscope. Flow cytometry was performed to detect cell transfection
      efficiency. The expressions of cardiac-specific proteins connexin 43 (Cx43),
      cardiac troponin T (cTnT) and genes GATA binding protein 4 (GATA4), myocyte
      enhancer factor 2C (MEF2C) were analyzed by Western blotting, immunofluorescence
      and real-time quantitative PCR (qRT-PCR). RESULTS: High-titer recombinant
      adenovirus was generated with HEK293 cells. The expressions of Cx43, cTnT, GATA4
      and MEF2C were similar among Wnt3a group, GFP group and control group, but they
      significantly increased in cells when co-induced by Wnt3a and BMP9 for 3 weeks.
      The expressions of Cx43, cTnT, GATA4 and MEF2C showed no significant difference
      between BMP9 group and Wnt3a and BMP9 co-induction group. CONCLUSION: Wnt3a can
      not promote the differentiation of C3H10T1/2 cells into cardiomyocyte-like cells
      by itself, but co-induction by Wnt3a and BMP9 can promote the differentiation.

PMID- 25854559
TI  - [Protective effect of paeoniflorin on the hippocampus in rats with cerebral
      ischemia-reperfusion through activating cannabinoid receptor 2].
AB  - OBJECTIVE: To investigate the protective effect of paeoniflorin on hippocampal
      neurons in rats subjected to cerebral ischemia and reperfusion through activating
      cannabinoid receptor 2 (CBR2). METHODS: A total of 144 male SD rats were randomly
      divided into sham-operation group, cerebral ischemia-reperfusion model group,
      menstruum group, 10 and 40 mg/kg paeoniflorin groups, 3 mg/kg CBR2 selective
      antagonist AM630 group, 40 mg/kg paeoniflorin combined with 3 mg/kg AM630 group,
      and 3 mg/kg CBR2 selective agonist HU308 treatment group. Focal cerebral ischemia
      reperfusion models were made by inserting a monofilament suture into internal
      carotid artery. The neurological scores, infarction volume and cerebral edema
      were detected carefully to find out the effect of paeoniflorin on neurons.
      Pathological changes were observed by HE staining. The expressions of caspase-3
      and cyclooxygenase 2 (COX-2) in hippocampal CA1 region were determined by
      immunohistochemistry. RESULTS: Paeoniflorin significantly decreased the
      neurological scores, infarction volume and cerebral edema. In addition,
      paeoniflorin relieved the pathological changes and inhibited the expressions of
      caspase-3 and COX-2 in hippocampus CA1 area. But injecting AM630 in advance
      obviously counteracted the neuroprotective effect of paeoniflorin. CONCLUSION:
      CBR2 may participate in the protective effect of paeoniflorin on hippocampal
      neurons of cerebral ischemia-reperfusion rat models.

PMID- 25854561
TI  - [Recombinant adenovirus of microRNA-193b inhibits proliferation of K562 cells].
AB  - OBJECTIVE: To construct a recombinant adenovirus vector containing human pre-miR
      193b and investigate its effect on the proliferation of chronic myelocytic
      leukemia K562 cells. METHODS: The cDNA of pre-miR-193b was obtained by chemical
      synthesis and inserted into the adenoviral shuttle vector pAdTrack-CMV. The
      recombinant shuttle plasmid was linearized by Pme I and transformed into AdEasier
      cells for homologous recombination in E.coli BJ5183 with the adenoviral backbone
      plasmid pAdEasy-1. The recombinant adenoviral plasmid was linearized by Pac I and
      then used for transfecting HEK293 cells. After package and amplification in
      HEK293 cells, the virus titer was determined by serial dilution assay. The
      expression level of miR-193b in K562 cells was detected by real-time quantitative
      PCR. The cell proliferation was observed by MTT assay. RESULTS: The recombinant
      plasmid named pAd-miR-193b was confirmed by restriction enzyme analysis and
      sequencing. The recombinant adenovirus could infect K562 cells efficiently.
      Compared with control group, real-time quantitative PCR revealed that the
      expression of miR-193b was significantly up-regulated in K562 cells infected with
      pAd-pre-miR-193b, and the cell proliferation was suppressed significantly in K562
      cells with up-regulated miR-193b expression. CONCLUSION: The over-expression of
      miR-193b may suppress the proliferation of K562 cells.

PMID- 25854562
TI  - [The transfection of lentiviral siRNA vectors targeting ezrin, radixin and moesin
      facilitates influenza virus replication in primary pulmonary microvascular
      endothelial cells].
AB  - OBJECTIVE: To construct lentivirus siRNA vectors targeting ezrin (E), radixin (R)
      and moesin (M), transfect rat primary pulmonary microvascular endothelial cells
      (PMVECs) with the vectors and observe the effects of the transfection on E, R, M
      gene expressions and influenza virus replication. METHODS: According to the
      principles of siRNA synthesis, siRNA sequences targeting E, R and M genes were
      synthesized and cloned into lentiviral plasmid GV248 to construct lentiviral
      siRNA vectors Lenti-E-siRNA, Lenti-R-siRNA and Lenti-M-siRNA, respectively.
      Random Lenti-control-siRNA was also constructed targeting nonsense sequences. Rat
      PMVECs were cultured by peripheral lung tissue-sticking method. Rat PMVECs were
      transfected with Lenti-E-siRNA, Lenti-R-siRNA and Lenti-M-siRNA, respectively.
      The levels of ezrin, radixin and moesin mRNA and proteins were detected by real
      time quantitative PCR and Western blotting, the distributions of ERM proteins
      were detected using confocal laser scanning microscope; After lentivirus
      transfected PMVECs were infected with influenza virus, the effects of lentiviral
      vectors on influenza virus replication were measured by real-time quantitative
      PCR. RESULTS: Lenti-E-siRNA, Lenti-R-siRNA, Lenti-M-siRNA and Lenti-control-siRNA
      were successfully constructed according to sequencing identification of
      recombinant plasmids. The infection efficacy of lentiviral siRNA vectors in rat
      PMVECs was above 80% at a multiplicity of infection (MOI) of 10. The
      transcription and expressions of ezrin, radixin and moesin in rat PMVECs were
      significantly inhibited by Lenti-E-siRNA, Lenti-R-siRNA, Lenti-M-siRNA
      respectively. Lentivirus control (containing no target genes) and Lenti-control
      siRNA inhibited influenza virus replication in influenza virus-infected PMVECs,
      while Lenti-E-siRNA, Lenti-R-siRNA and Lenti-M-siRNA increased the levels of
      influenza virus mRNA in the infected PMVECs. CONCLUSION: Lentiviral siRNA vectors
      targeting E, R and M genes were constructed successfully and could inhibit E, R
      and M gene expressions specifically and effectively. Lentiviral vectors could
      inhibit influenza virus replication whereas lentiviral siRNA vectors targeting E,
      R and M facilitated influenza virus replication.

PMID- 25854563
TI  - [Cross immunogenicity between Ia-associated invariant chains of chicken (Gallus
      domestiaus) and Muscovy duck (Cairina moschata)].
AB  - OBJECTIVE: To explore the cross immunogenicity between Ia-associated invariant
      chain (Ii) of chicken (CIi) and Ii of Muscovy duck (MDIi). METHODS: The
      immunoreactivity between mouse anti-CIi serum and the MDIi expressed by
      prokaryotic cell, and the immunoreactivity between the mouse anti-MDIi serum and
      the CIi expressed by prokaryotic cell were detected through indirect ELISA. To
      detect the immunoreactivity between the mouse anti-CIi serum and the MDIi of the
      spleen tissues of Muscovy duck, and the immunoreactivity between the mouse anti
      MDIi serum and the CIi of the liver tissues of chicken (tissular CIi), the
      fluorescence immunohistochemistry assay was performed using DyLight 488
      affiniPure goat anti-mouse IgG as the second antibody. The fluorescence intensity
      was detected in each tissue by Leica fluorescence microscopic imaging system.
      RESULTS: The titer of ELISA reactivity between mouse anti-MDIi serum and the
      expressed CIi was 1:8000. The titer of ELISA reactivity between mouse anti-CIi
      serum and the expressed MDIi was 1:16 000. The mouse anti-CIi serum and anti-MDIi
      serum could respectively react with tissular MDIi and tissular CIi, showing
      visible green fluorescence in corresponding cells of each tissue. But the
      fluorescence intensities in the above tissues were weaker than those in positive
      control tissues in which the mouse anti-MDIi serum or anti-CIi serum reacted with
      tissular MDIi or tissular CIi respectively. CONCLUSION: The cross immunogenicity
      between CIi and MDIi has been verified through the immunological experiments. The
      molecular basis of common antigen epitope formation between CIi and MDIi involves
      the conservation of the two Ii sequences, which reveals the high conservative
      property of Ii among variant birds from the perspective of immunology.

PMID- 25854564
TI  - [Detection and correlation analysis of miRNAs and myeloid-derived suppressor
      cells in ovarian cancer-bearing mice].
AB  - OBJECTIVE: To detect the levels of miR-21a-5p, miR-155-5p, miR-218-5p, miR-222
      3p, miR-494-3p in ovarian cancer tissues and the number of myeloid-derived
      suppressor cells (MDSCs) in peripheral blood and spleen in ovarian cancer-bearing
      mice, and explore their clinical significance and correlations. METHODS: The mRNA
      expressions of miR-21a-5p, miR-155a-5p, miR-218-5p, miR-222-3p, miR-494-3p were
      detected by real-time quantitative PCR (qRT-PCR) in tumor tissues and tumor
      adjacent normal tissues from 12 ovarian cancer-bearing mice. The frequency of
      MDSCs in the peripheral blood and spleen from the 12 tumor-bearing mice was
      measured by flow cytometry. Spearman correlation analysis was used to find out
      the correlations between MDSCs and miRNAs. RESULTS: Compared with the normal
      mice, the number of MDSCs in the peripheral blood and spleen of the tumor-bearing
      mice significantly increased. The levels of miR-21a-5p, miR-218-5p and miR-222-3p
      in tumor tissues were significantly higher than those in tumor-adjacent normal
      tissues; conversely, miR-155a-5p and miR-494-3p levels in the former were
      significantly lower than those in the latter. There was no correlation between
      miR-222-3p and MDSCs, but miR-494-3p had a negative correlation with MDSCs. The
      expression differences of miR-21a-5p, miR-155a-5p, miR-218-5p between tumor
      tissues and tumor-adjacent normal tissues had positive correlations with the
      number of MDSCs. CONCLUSION: The levels of miR-21a-5p, miR-155a-5p, miR-218-5p,
      miR-494-3p in tumor tissues had correlations with the number of MDSCs in the
      peripheral blood and spleen of ovarian cancer-bearing mice.

PMID- 25854565
TI  - [Whole blood leukocyte phagocytosis assay for Candida albicans based on flow
      cytometry].
AB  - OBJECTIVE: To establish a whole blood leukocyte phagocytosis assay for Candida
      albicans (C.albicans) based on flow cytometry (FCM). METHODS: C.albicans of mid
      logarithmic growth phase was labeled by fluorescence probe carboxyfluorescein
      diacetate succinimidyl ester (CFDA-SE), and then added into CD45-PC5 pre-stained
      human whole blood cells at a 10:1 multiplicity of infection (MOI) in
      37DegreesCelsius. The cells were incubated for 10, 30 and 60 minutes.
      Phagocytosis rate of C.albicans by the CD45 positive cells in the blood was
      determined by FCM. RESULTS: In yeast extract peptone dextrose medium (YPD) and
      under the conditions of 37DegreesCelsius and 50 mL/L CO2, the logarithmic growth
      phase of C.albicans SC5314 was from the 5th to 11th hour. C.albicans were well
      stained by 10 mmol/L CFDA-SE after 30-minute incubation. After 10-, 30- and 60
      minute incubation with SC5314 C.albicans with CD45+ cells, the phagocytosis rates
      measured by FCM were (80.1 +/- 6.1)%, (83.8 +/- 7.7)% and (92.3 +/- 11.2)% for
      the neutrophils, (11.2 +/- 3.6)%, (15.8 +/- 4.4)% and (27.7 +/- 6.8)% for the
      monocytes and (0.9 +/- 0.3)%, (0.8 +/- 0.4)% and (5.2 +/- 1.6)% for the
      lymphocytes. CONCLUSION: The method for measuring whole blood leukocyte
      phagocytosis of C.albicans based on FCM is successfully established, and 30
      minutes are the proper incubation time for the phagocytosis assay.

PMID- 25854566
TI  - [Prediction of epitopes of Rv1410c Mycobacterium tuberculosis protein using
      DNAStar software].
AB  - OBJECTIVE: To predict the epitopes of Rv1410c Mycobacterium tuberculosis (MTB)
      protein. METHODS: Rv1410c MTB amino acid sequence was saved and edited using
      Editseq software of DNAStar package, and then Protean software was used to
      analyze the amino acid sequence and predict the secondary structures, B cell
      epitopes and T cell epitopes of Rv1410c MTB. Finally, BLAST was utilized to
      assess its homology with human epitopes. RESULTS: The Rv1410c MTB protein had
      abundant secondary structures. It contained a higher proportion of potential B
      cell epitopes located at 1-10, 67-77, 129-137, 189-205, 222-235, 253-267, 296
      306, 330-338, 359-367, 462-467, 494-517 amino acid residues or nearby. Theses
      epitopes contained beta angle structure mostly, presenting with better
      antigenicity, higher surface probability and flexibility. There were also several
      potential T cell epitopes located at 16-37, 84-102, 108-115, 137-160, 202-207,
      219-222, 245-263, 321-325, 355-362, 387-391, 417-445, 486-494 amino acid residues
      or nearby. CONCLUSION: Rv1410c MTB protein contains both potential B cell antigen
      epitopes and potential T cell antigen epitopes.

PMID- 25854567
TI  - [The extract of blackend swallowwort root up-regulates the expressions of
      angiogenesis related proteins and promotes liver angiogenesis of mice with
      partial hepatectomy].
AB  - OBJECTIVE: To observe the effects of the extract of blackend swallowwort root
      (EBSR) on neovascularization after partial hepatectomy and explore the
      corresponding molecules and mechanism of the regulation. METHODS: Twenty mice
      were randomly divided into control group and EBSR group. Mice in the two groups
      were subjected to a one-time resection of part of the left lateral lobe of the
      liver. The mice in the experimental group were treated with EBSR by intragastric
      administration at a dose of 50 g/kg, twice per day after operation. During the
      eight days after the operation, one mouse in each group was sacrificed every day
      and the left lateral liver lobe was harvested. Immunohistochemistry was used to
      detect the expressions of vascular endothelial growth factor-C (VEGF-C), VEGF-A,
      lymphatic vessel endothelial HA receptor-1 (LYVE-1) and CD34. RESULTS: Compared
      with the control group, the significantly increased expression of CD34 in mice of
      the EBSR group was observed, as well as expanded distribution. Also, a decrease
      in the early phase but a significant increase in the latter was seen in the
      expressions of VEGF-C, VEGF-A and LYVE-1. CONCLUSION: EBSR can up-regulate the
      expressions of VEGF-C, VEGF-A and LYVE-1 so as to promote liver angiogenesis of
      mice with partial hepatectomy.

PMID- 25854568
TI  - [Saponin 6 of Anemone Taipaiensis inhibits proliferation and induces apoptosis of
      U87 MG cells].
AB  - OBJECTIVE: To investigate the effect of saponin 6 of Anemone Taipaiensis on the
      proliferation of human U87 MG glioma cells and the possible mechanism. METHODS:
      U87 MG cells were treated with different concentrations of saponin 6 (0.0, 1.6,
      3.2, 6.4, 12.8 MUg/mL) for 24 hours or 48 hours. Cell viability was measured by
      MTT assay; the apoptosis rate was detected by flow cytometry combined with
      annexin V-FITC /PI staining; Western blotting was applied to determine the
      protein level of activated caspase-3. RESULTS: Compared with control groups,
      saponin 6 significantly inhibited U87 MG cell proliferation in a time- and dose
      depended manner. Apoptosis rate of U87 MG cells and the expression of activated
      caspase-3 were raised with the increasing concentration of saponin 6. CONCLUSION:
      Saponin 6 of Anemone Taipaiensis could depress cell proliferation in a dose
      depended manner, increase the expression of activated caspase-3 and promote
      apoptosis in U87 MG cells.

PMID- 25854569
TI  - [Sodium butyrate down-regulates IFN-gamma-induced indoleamine 2, 3 dioxygenase
      and promotes its acetylation and ubiquitination in CNE2 nasopharyngeal carcinoma
      cells].
AB  - OBJECTIVE: To investigate molecular mechanisms of posttranslational regulation of
      sodium butyrate (NaB) on indoleamine 2, 3-dioxygenase (IDO) expression induced by
      interferon gamma (IFN-gamma) in CNE2 nasopharyngeal carcinoma cells. METHODS:
      Western blotting and co-immunoprecipitation assay were used to detect the
      expression, acetylation and ubiquitination of IDO in CNE2 nasopharyngeal
      carcinoma cells. RESULTS: Western blotting demonstrated that while the cells were
      treated with IFN-gamma and NaB compared with IFN-gamma treatment only, the
      expression of IDO protein increased significantly; furthermore, in the co
      immunoprecipitation assay, while the cells were treated with IFN-gamma and NaB
      compared with the ones treated with IFN-gamma only, acetylation and
      ubiquitination of IDO increased significantly. Western blotting showed that the
      cells treated with NaB and IFN-gamma presented with lower IDO protein expression
      than the ones treated with NaB, IFN-gamma and bortezomib simultaneously.
      CONCLUSION: NaB could down-regulate the expression of IDO induced by IFN-gamma in
      a dose-dependent manner, and the combined treatment of IFN-gamma and NaB could
      promote the acetylation and ubiquitination of IDO in CNE2 nasopharyngeal
      carcinoma cells.

PMID- 25854570
TI  - [Construction and application of a recombinant plasmid inducing cell death in
      hepatocytes after transfection].
AB  - OBJECTIVE: The mechanisms of mesenchymal stromal cells (MSCs)-mediated treatment
      of liver damage have been unclear. Two major mechanisms, which involve paracrine
      effects and/or direct trans-differentiation, have been proposed. To clarify which
      mechanism is more important, we planned to construct a recombinant plasmid
      expressing green fluorescent protein (GFP) driven by the cytomegalovirus (CMV)
      promoter and Pseudomonas aeruginosa exotoxin 40 (PE40) driven by the albumin
      (alb) promoter, which can induce cell death as soon as MSCs differentiate into
      hepatocytes. METHODS: To construct the recombinant eukaryotic expression vector
      pFlag-CMV-GFP-TM-albp-PE40, GFP, transmembrane domain of DLL1, alb promoter and
      PE40 were obtained by PCR and were inserted into pFlag-CMV-1. The expression of
      GFP was observed under a fluorescence microscope and the killing effect on
      hepatocytes was analyzed by flow cytometry. RESULTS: The recombinant plasmid
      inducing cell death in hepatocytes was successfully constructed, suggesting that
      the plasmid could be employed to study the mechanism of MSCs-mediated treatment
      on liver damage. CONCLUSION: This study might provide a promising tool for
      revealing the mechanism of MSCs-mediated treatment on liver diseases.

PMID- 25854571
TI  - [Etanercept inhibits synovial inflammation and reduces the expression of adhesion
      related molecules in synovial tissues of patients with rheumatoid arthritis].
AB  - OBJECTIVE: To observe the changes of synovial inflammation score and expression
      of related molecular markers in patients with rheumatoid arthritis treated with
      tumor necrosis factor (TNF) antagonist etanercept. METHODS: Sixteen patients with
      rheumatoid arthritis received synovectomy in the knee under arthroscopy, of which
      8 patients had been treated with etanercept before surgery (etanercept group) and
      the other 8 patients were given no etanercept or other biologics (non-biological
      agent group). The synovial tissues obtained from surgery were subjected to HE
      staining and immunohistochemical staining respectively, to assess Rooney's
      inflammation score and detect the expressions of proliferating cell nuclear
      antigen (PCNA), vascular cell adhesion molecule-1 (VCAM-1), intercellular
      adhesion molecule-1 (ICAM-1) and cadherin-11. RESULTS: Rooney's score in
      etanercept group was significantly lower than that in non-biological agent group.
      The expressions of PCNA and cadherin-11 in synovial lining and sublining layers
      significantly decreased in etanercept group. Expressions of VCAM-1 and ICAM-1 had
      no significant difference in either synovial lining or sublining layer between
      the two groups. Clinical inflammatory markers including erythrocyte sedimentation
      rate (ESR), C-reactive protein (CRP), platelet count (PLT) and disease activity
      score in 28 joints (DAS28) had no statistical correlation with Rooney's
      inflammation score. CONCLUSION: Etanercept could effectively inhibit
      proliferation of synoviocytes and infiltration of lymphocytes in synovium of
      rheumatoid arthritis, and decrease the expressions of proliferation-and adhesion
      related molecular markers, which histologically alleviated the synovial
      inflammation of rheumatoid arthritis. Clinical inflammatory markers might not
      fully reflect histological changes in the local synovial tissue.

PMID- 25854572
TI  - [Expressions and significance of NDRG2 and Bcl-2 in human gastric cancer
      tissues].
AB  - OBJECTIVE: To analyze the expressions of N-myc downstream regulated gene 2
      (NDRG2) and B cell lymphoma/leukemia-2 (Bcl-2) in human gastric cancer in an
      attempt to explore their correlation and clinical significance. METHODS:
      Immunohistochemical staining was used to detect the expression of NDRG2 and Bcl-2
      in human gastric cancer, para-carcinoma tissues and normal tissues. The
      correlation between their expressions and clinicopathologic data were analyzed
      using statistical software in gastric cancer tissues. RESULTS: The tissue
      microarray consisting of 64 gastric cancer and 10 normal gastric tissues showed
      NDRG2 expression in gastric cancer tissues was significantly lower than that in
      normal tissues, whereas Bcl-2 expression in gastric cancer tissues was
      significantly higher than that in normal tissues. It was also indicated that
      NDRG2 was negatively correlated with Bcl-2 in gastric cancer tissues. NDRG2 and
      Bcl-2 were further analyzed in 206 gastric cancer and paired para-carcinoma
      tissues. It was displayed that the expression levels of NDRG2 and Bcl-2 in human
      gastric cancer were not associated with age and sex, but significantly associated
      with tumor differentiation, clinical stage and lymph node metastasis. CONCLUSION:
      There is a negative correlation between NDRG2 and Bcl-2 expressions in human
      gastric cancer, suggesting they might be synergistically involved in the
      development of gastric cancer.

PMID- 25854573
TI  - [Clinical detection and significance of plasma IL-37 in patients with active
      pulmonary tuberculosis].
AB  - OBJECTIVE: To investigate the level of plasma interleukin 37 (IL-37) and explore
      the clinical significance of IL-37 in patients with active pulmonary tuberculosis
      (ATB). METHODS: ELISA was used to detect the level of plasma IL-37 from 30
      patients with ATB, 15 patients who had been treated for ATB, and 21 healthy
      volunteers as controls. RESULTS: The level of plasma IL-37 in patients with ATB
      was significantly higher than that in healthy controls. The monitoring on the 15
      patients showed that plasma IL-37 was reduced after treatment for ATB. The level
      of plasma IL-37 in patients with anti-Mycobecterium tuberculosis antibody
      positive or sputum smear positive were higher than that in patients with anti
      Mycobecterium tuberculosis antibody negative or sputum smear negative for
      Mycobecterium tuberculosis, and the level was negatively correlated with the
      number of white blood cells in peripheral blood. CONCLUSION: The patients with
      ATB present with significantly increased level of plasma IL-37, which might be an
      indicator of curative effect in ATB.

PMID- 25854574
TI  - [HLA-E gene polymorphisms and plasma soluble HLA-E levels and their relationship
      with genetic susceptibility to breast cancer].
AB  - OBJECTIVE: To investigate the association of human leukocyte antigen-E (HLA-E)
      gene polymorphisms and plasma soluble HLA-E (sHLA-E) levels with genetic
      susceptibility to breast cancer in Zhangjiakou women of Han nationality. METHODS:
      HLA-E typing was performed in 200 patients with breast cancer and 228 healthy
      controls from Zhangjiakou area by means of polymerase chain reaction-sequence
      specific priming (PCR-SSP). Simultaneously, sHLA-E was detected by ELISA.
      RESULTS: We found two alleles of HLA-E: HLA-E*0101 and HLA-E*0103, and three
      genotypes, namely HLA-E*0101/HLA-E*0101, HLA-E*0101/HLA-E*0103 and HLA-E*0103/HLA
      E*0103. The frequencies of HLA-E*0103 allele and HLA-E*0103/HLA-E*0103 genotype
      showed a significant difference between healthy controls and patients with breast
      cancer. The HLA-E*0103/HLA-E*0103 genotype significantly increased the risk for
      breast cancer. Plasma levels of sHLA-E showed no significant difference in breast
      cancer patients and controls. While in breast cancer patients with HLA-E*0103/HLA
      E*0103 genotype, plasma levels of sHLA-E were significantly elevated compared
      with those in healthy controls. HLA-E genotypes and sHLA-E levels had no obvious
      relationship with tumor grading. CONCLUSION: HLA-E gene polymorphisms are
      associated with the development of breast cancer in Zhangjiakou women of Han
      nationality. HLA-E*0103/HLA-E*0103 genotype is probably susceptible genotype for
      breast cancer, while plasma sHLA-E level probably has no association with breast
      cancer susceptibility.

PMID- 25854575
TI  - [Cefodizime increases peripheral blood CD4/CD8 and Th1/Th2 ratios in senile
      patients with bacterial pneumonia].
AB  - OBJECTIVE: To explore the influence of cefodizime on CD4/CD8 and T helper
      1(Th1)/Th2 cell ratios in peripheral blood of the senile patients with bacterial
      pneumonia. METHODS: Sixty-three senile patients with bacterial pneumonia were
      enrolled and divided into two groups randomly. Patients in the control group
      (n=31) were given intravenous infusion of ceftriaxone sodium, and patients in the
      observation group (n=32) were given intravenous infusion of cefodizime. The
      fasting venous blood was taken before and after treatment to detect CD4/CD8 and
      Th1/Th2 cell ratios with flow cytometry. At the same time, the serum interleukin
      2 (IL-2), interferon gamma (IFN-gamma), IL-4 and IL-10 contents were also
      detected with ELISA. RESULTS: Before treatment, there was no significant
      difference in the above indexes between the two groups. After treatment, CD4+
      cells and Th1 cells of the observation group increased while Th2 cells decreased;
      as a result, the CD4/CD8 and Th1/Th2 cell ratios of the observation group were
      significantly higher than those of the control group. At the same time, serum IL
      2 and IFN-gamma contents of the observation group were significantly higher than
      those of the control group, while serum IL-4 and IL-10 contents were
      significantly lower than those of the control group. CONCLUSION: Cefodizime can
      improve the cellular immune function and rectify CD4/CD8 and Th1/Th2 imbalance in
      peripheral blood of the senile patients with bacterial pneumonia.

PMID- 25854576
TI  - [NRH2 induces cell apoptosis of cerebral tissues around hematomas after
      intracerebral hemorrhage through up-regulating proNGF, sortilin and p75NTR
      expressions].
AB  - OBJECTIVE: To observe the expressions of neurotrophin receptor homolog 2 (NRH2),
      nerve growth factor precursor (proNGF), sortilin and neurotrophin receptor p75
      (p75NTR) in cerebral tissues around hematomas in the different periods after
      intracerebral hemorrhage, and explore their relationships to cell apoptosis.
      METHODS: The specimens of cerebral tissues around hematomas were collected from
      the patients undergoing hematoma removal operation after intracerebral
      hemorrhage. These specimens were divided into four groups, namely <= 6 hours, 6
      24 hours(including 24 hours), 24-72 hours (including 72 hours) and over 72 hours
      according to the time from intracerebral hemorrhage to specimen collection. At
      the same time, 10 brain tissues distant to hemorrhage that dropped in the
      operative process were collected as a control group. Apoptosis index (AI) was
      examined in brain cells by terminal deoxynucleotidyl transferase mediated
      deoxyuridine triphosphate nick end labeling (TUNEL). The expressions of NRH2,
      proNGF, sortilin and p75NTR mRNAs and proteins in brain tissues were detected
      through real-time quantitative PCR and Western blotting, respectively. Also, the
      expressions of Bcl-2 and Bax in brain tissues were analyzed using Western
      blotting. In vitro cultured astrocytes of rat cortex were transfected by NRH2
      siRNA or scramble siRNA. The expressions of proNGF, sortilin and p75NTR proteins
      were detected using Western blotting. RESULTS: AI was higher in all groups of
      hemorrhage for 6 hours or longer than that in control and <= 6 hours groups, and
      AI in the group of 24-72 hours after intracerebral hemorrhage was the highest.
      However, there was no significant difference in AI between <= 6 hours group and
      control group. With the extension of intracerebral hemorrhage time, the
      expression levels of proNGF and p75NTR mRNAs and proteins were gradually
      elevated, reached the peak in 24-72 hours, and maintained a higher level after 72
      hours, whereas there were no significant differences in the above indicators
      between <= 6 hours group and control group. In comparison with control group and
      <= 6 hours group, the expression levels of NRH2 and sortilin mRNAs and proteins
      and Bax expression started to increase in 6-24 hours, reached the peak in 24-72
      hours, and then stayed a higher level after 72 hours, whereas there were no
      significant differences in the above indicators between <= 6 hours group and
      control group. There was no obvious change in Bcl-2 expression level between <= 6
      hours group and control group. The level of Bcl-2 decreased in all groups of
      intracerebral hemorrhage for over 6 hours, and reached the nadir in 24-72 hours.
      Astrocytes transfected with NRH2 siRNA displayed a significant decrease in
      proNGF, sortilin and p75NTR protein levels as compared with scramble siRNA or
      blank control groups. CONCLUSION: The expression of NRH2 would increase in the
      cerebral tissues around hematomas after intracerebral hemorrhage. NRH2 might
      enhance the ratio of Bax/Bcl-2 by promoting the expressions of proNGF, sortilin
      and p75NTR, thereby inducing brain cell apoptosis.

PMID- 25854577
TI  - [Preparation and characterization of monoclonal antibodies against F domain of
      human progranulin].
AB  - OBJECTIVE: To prepare and characterize the monoclonal antibody (mAb) against F
      domain of human progranulin (GrnF). METHODS: Yeast expression vector containing
      GrnF gene was constructed using molecular biological technology. Then eukaryotic
      fusion protein human serum albumin (HSA)-GrnF from yeast vector was expressed and
      purified. BALB/c mice were immunized by the purified HSA-GrnF fusion protein. The
      splenocytes of the BALB/c mice were isolated from spleen and fused with Sp2/0
      myeloma cells. Indirect ELISA and limiting dilution assay were used for screening
      hybridoma cell lines. The specificity of monoclonal antibodies against GrnF was
      evaluated with indirect ELISA, Western blotting and immunohistochemistry. The
      immunoglobulin subclass was identified with mouse monoclonal antibody isotyping
      reagents. RESULTS: Two hybridoma cell lines, 1G6 and 4E8, were obtained and heavy
      chain subclasses of the two hybridoma cell lines were IgG1. CONCLUSION: The mAbs
      that can specifically recognize GrnF have been successfully prepared.

PMID- 25854578
TI  - [Preparation and identification of the polyclonal antibody against human insulin
      like growth factor 2 mRNA-binding protein 3].
AB  - OBJECTIVE: To construct the prokaryotic expression vector of insulin-like growth
      factor 2 mRNA-binding protein 3 (IGF2BP3), express and purify IGF2BP3 protein in
      E.coli, and prepare the polyclonal antibody against IGF2BP3. METHODS: The full
      open reading frame (ORF) of human IGF2BP3 was amplified by PCR, subcloned into
      pET-28a vector, and transformed into E.coli BL21(DE3), in which expression of the
      His-tagged IGF2BP3 protein was induced by IPTG. This protein was subsequently
      purified by Ni-NTA purification system, refolded by removal of urea from the
      solution. BALB/c mice were immunized with the purified IGF2BP3 protein to produce
      polyclonal antibody against IGF2BP3. The resulting anti-sera were further
      characterized by ELISA, Western blotting and immunohistochemistry. RESULTS:
      IGF2BP3 gene we amplified was consistent with the sequence reported by GenBank.
      Prokaryotic expression vector pET-28a-IGF2BP3 was constructed. His-tagged IGF2BP3
      protein was successfully expressed in BL21 (DE3) with relative molecular mass
      (Mr) about 70 000 after IPTG induction. After purified by Ni-NTA resin, the
      purity of the protein reached above 90%. After immunization, the titer of the
      IGF2BP3 mouse anti-serum was over 1:50 000 as determined by ELISA. Further,
      Western blotting and immunohistochemistry showed that the IGF2BP3 antibody could
      specifically recognize the target protein. CONCLUSION: The polyclonal antibody
      specifically recognizing IGF2BP3 has been successfully generated.

PMID- 25854579
TI  - Emerging roles for PIWI proteins in cancer.
AB  - It is generally accepted that PIWI proteins are predominately expressed in the
      germline but absent in somatic tissues. Their best-characterized role is to
      suppress transposon expression, which ensures genomic stability in the germline.
      However, increasing evidence has suggested that PIWI proteins are linked to the
      hallmarks of cancer defined by Weinberg and Hanahan, such as cell proliferation,
      anti-apoptosis, genomic instability, invasion and metastasis. This provides new
      possibilities for anticancer therapies through the targeting of PIWI proteins,
      which may have fewer side effects due to their potential classification as a CTA
      (cancer/testis antigen). Furthermore, PIWI has been proposed to act as a
      diagnostic and prognostic marker for many types of cancer, and even to
      differentiate early- and late-stage cancers. We herein summarize the latest
      progress in this exciting field, hoping to encourage new investigations of PIWIs
      in cancer biology that will help to develop new therapeutics for clinical
      application. 

PMID- 25854580
TI  - Data analysis as a source of variability of the HLA-peptide multimer assay: from
      manual gating to automated recognition of cell clusters.
AB  - Multiparameter flow cytometry is an indispensable method for assessing antigen
      specific T cells in basic research and cancer immunotherapy. Proficiency panels
      have shown that cell sample processing, test protocols and data analysis may all
      contribute to the variability of the results obtained by laboratories performing
      ex vivo T cell immune monitoring. In particular, analysis currently relies on a
      manual, step-by-step strategy employing serial gating decisions based on visual
      inspection of one- or two-dimensional plots. It is therefore operator dependent
      and subjective. In the context of continuing efforts to support inter-laboratory
      T cell assay harmonization, the CIMT Immunoguiding Program organized its third
      proficiency panel dedicated to the detection of antigen-specific CD8(+) T cells
      by HLA-peptide multimer staining. We first assessed the contribution of manual
      data analysis to the variability of reported T cell frequencies within a group of
      laboratories staining and analyzing the same cell samples with their own reagents
      and protocols. The results show that data analysis is a source of variation in
      the multimer assay outcome. To evaluate whether an automated analysis approach
      can reduce variability of proficiency panel data, we used a hierarchical
      statistical mixture model to identify cell clusters. Challenges for automated
      analysis were the need to process non-standardized data sets from multiple
      centers, and the fact that the antigen-specific cell frequencies were very low in
      most samples. We show that this automated method can circumvent difficulties
      inherent to manual gating strategies and is broadly applicable for experiments
      performed with heterogeneous protocols and reagents.

PMID- 25854581
TI  - Role of NKG2D, DNAM-1 and natural cytotoxicity receptors in cytotoxicity toward
      rhabdomyosarcoma cell lines mediated by resting and IL-15-activated human natural
      killer cells.
AB  - Children with advanced stages (relapsed/refractory and stage IV) of
      rhabdomyosarcoma (RMS) have a poor prognosis despite intensive chemotherapy and
      autologous stem cell rescue, with 5-year survival rates ranging from 5 to 35 %.
      Development of new, additional treatment modalities is necessary to improve the
      survival rate. In this preclinical study, we investigated the potential of
      resting and cytokine-activated natural killer (NK) cells to lyse RMS cell lines,
      as well as the pathways involved, to explore the eventual clinical application of
      (activated) NK cell immunotherapy. RMS cell lines (n = 3 derived from embryonal
      RMS and n = 2 derived from alveolar RMS) were susceptible to cytolysis mediated
      by resting NK cells, and this susceptibility was significantly increased using IL
      15-activated NK cells. Flow cytometry and cytolytic assays were used to define
      the activating and inhibitory pathways of NK cells involved in recognizing and
      lysing RMS cells. NKG2D and DNAM-1 receptor-ligand interactions were essential in
      cytolysis by resting NK cells, as simultaneous blocking of both pathways resulted
      in almost complete abrogation of the cytotoxicity. In contrast, combined blocking
      of DNAM-1 and NKG2D only led to partial reduction of the lytic activity of IL-15
      activated NK cells. In this respect, residual lysis was, at least partly,
      mediated by pathways involving the natural cytotoxicity receptors NKp30 and
      NKp46. These findings support further exploration of NK cell-based immunotherapy
      as adjuvant modality in current treatment strategies of RMS.

PMID- 25854582
TI  - Broadening the repertoire of melanoma-associated T-cell epitopes.
AB  - Immune therapy has provided a significant breakthrough in the treatment of
      metastatic melanoma. Despite the remarkable clinical efficacy and established
      involvement of effector CD8 T cells, the knowledge of the exact peptide-MHC
      complexes recognized by T cells on the tumor cell surface is limited. Many
      melanoma-associated T-cell epitopes have been described, but this knowledge
      remains largely restricted to HLA-A2, and we lack understanding of the T-cell
      recognition in the context of other HLA molecules. We selected six melanoma
      associated antigens (MAGE-A3, NY-ESO-1, gp100, Mart1, tyrosinase and TRP-2) that
      are frequently recognized in patients with the aim of identifying novel T-cell
      epitopes restricted to HLA-A1, -A3, -A11 and -B7. Using in silico prediction and
      in vitro confirmation, we identified 127 MHC ligands and analyzed the T-cell
      responses against these ligands via the MHC multimer-based enrichment of
      peripheral blood from 39 melanoma patients and 10 healthy donors. To dissect the
      T-cell reactivity against this large peptide library, we used combinatorial
      encoded MHC multimers and observed the T-cell responses against 17 different
      peptide-MHC complexes in the patient group and four in the healthy donor group.
      We confirmed the processing and presentation of HLA-A3-restricted T-cell epitopes
      from tyrosinase (TQYESGSMDK) and gp100 (LIYRRRLMK) and an HLA-A11-restricted T
      cell epitope from gp100 (AVGATKVPR) via the cytolytic T-cell recognition of
      melanoma cell lines and/or K562 cells expressing the appropriate antigen and HLA
      molecule. We further found T-cell reactivity against two of the identified
      sequences among tumor-infiltrating lymphocytes from melanoma patients, suggesting
      a potential clinical relevance of these sequences.

PMID- 25854583
TI  - NZ28-induced inhibition of HSF1, SP1 and NF-kappaB triggers the loss of the
      natural killer cell-activating ligands MICA/B on human tumor cells.
AB  - The activity of natural killer (NK) cells is regulated by activating and
      inhibiting receptors, whereby the C-type lectin natural killer group 2D (NKG2D)
      receptor serves as the major activating receptor on NK cells which recognizes
      major histocompatibility class I chain-related proteins A and B (MICA/B). The
      MICA/B expression has been described to be regulated by the transcription factor
      heat shock factor 1 (HSF1). Inhibition of heat shock protein 90 (Hsp90) is known
      to induce the heat shock response via activation of HSF1 which is associated with
      tumor development, metastasis and therapy resistance and also with an increased
      susceptibility to NK cell-mediated lysis. Therefore, we compared the effects of
      Hsp90 inhibitor NVP-AUY922, HSF1 inhibitor NZ28 and HSF1 knockdown on the
      sensitivity of lung (H1339) and breast (MDA-MB-231, T47D) cancer cells to NK cell
      mediated cytotoxicity and the expression of the NKG2D ligands MICA/B. Although
      NVP-AUY922 activates HSF1, neither the MICA/B surface density on tumor cells nor
      their susceptibility to NK cell-mediated lysis was affected. A single knockdown
      of HSF1 by shRNA decreased the surface expression of MICB but not that of MICA,
      and thereby, the NK cell-mediated lysis was only partially blocked. In contrast,
      NZ28 completely blocked the MICA/B membrane expression on tumor cells and thereby
      strongly inhibited the NK cell-mediated cytotoxicity. This effect might be
      explained by a simultaneous inhibition of the transcription factors HSF1, Sp1 and
      NF-kappaB by NZ28. These findings suggest that new anticancer therapeutics should
      be investigated with respect to their effects on the innate immune system.

PMID- 25854585
TI  - Response to: 'The antibody response against human and chimeric anti-TNF
      therapeutic antibodies primarily targets the TNF binding region' by Rinaudo
      Gaujous et al.

PMID- 25854584
TI  - Differential DNA methylation and expression of inflammatory and zinc transporter
      genes defines subgroups of osteoarthritic hip patients.
AB  - OBJECTIVES: We have previously shown that the cartilage DNA methylome delineates
      two clusters of osteoarthritic (OA) hip patients, characterised by differential
      methylation of inflammatory genes, while others have demonstrated a link between
      zinc homeostasis and inflammation in OA. We aimed to investigate these effects at
      the methylation and gene expression level. METHODS: We used our previously
      generated methylation data while quantitative PCR was used to measure gene
      expression using RNA from the hip cartilage of members of both clusters and from
      control individuals without hip OA. RESULTS: One of the OA clusters is
      characterised by the promoter hypomethylation and increased expression of
      inflammation-associated genes including IL1A and TNF. Furthermore, we show that
      the increase in expression of these genes is accompanied by increased expression
      of several zinc transporter genes. In addition, the zinc responsive transcription
      factor MTF1 is also upregulated, which is accompanied by an increase in the
      expression of its targets the metalloproteinases MMP13 and ADAMTS5. CONCLUSIONS:
      We have identified a subgroup of OA hip patients that are epigenetically and
      transcriptiomically characterised by a cartilage inflammatory phenotype with
      concurrent differential regulation of zinc regulators. The identification of
      subgroups enhances stratified phenotyping of OA patients and has important
      implications for future therapeutic applications.

PMID- 25854586
TI  - Repeat cycles of rituximab on clinical relapse in ANCA-associated vasculitis:
      identifying B cell biomarkers for relapse to guide retreatment decisions.
AB  - OBJECTIVE: To assess clinical and B cell biomarkers to predict relapse after
      rituximab in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis
      (AAV) using retreatment on clinical relapse strategy. METHODS: 35 patients with
      AAV received treatment with 2*1000 mg rituximab, repeated on clinical relapse (up
      to 5 cycles). Disease activity was assessed by Birmingham Vasculitis Activity
      Score (BVAS) and peripheral B cell subsets using highly sensitive flow cytometry
      (HSFC) as previously described; both performed at baseline and every 3 months.
      RESULTS: Response rates were high: >83%, with median time-to-relapse of 82 weeks
      for cycle 1 (C1) and >54 weeks for all cycles. Prior to rituximab, AAV was
      characterised by naive B-lymphopenia compared to healthy controls. This
      dysregulation was more marked in patients with raised C-reactive protein (CRP)
      (p<0.05). In C1, no clinical feature predicted relapse. However, repopulation of
      naive B cell at 6 months was associated with a reduced risk of relapse (HR:
      0.326, 95% 0.114 to 0.930, p=0.036). Relapse rates at 12 and 18 months were 0%
      and 14% with naive repopulation at 6 months, and 31% and 54% without naive
      repopulation. CONCLUSIONS: Responses to B cell depletion therapy are long-lasting
      and relapse post-treatment may be predicted by absence of naive B cell
      repopulation at 6 months. Naive B-lymphopenia may be a biomarker of disease
      activity in AAV.

PMID- 25854587
TI  - Psychosexual Characteristics of Women Reporting Sexual Aggression Against Men.
AB  - Sexual aggression as committed by women has been the target of little empirical
      research and is still regarded as a myth by many people. The aim of this study
      was to evaluate the psychosexual profile of young and educated women reporting
      sexual aggression against men. This is a cross-sectional study; a total of 260
      female college students answered to an online survey. Among them, 93 (35.8%)
      reported having committed some form of sexual aggression against men: 46.2% of
      sexually aggressive women fell into the category of sexual coercion, 34.1% fell
      into the category of sexual abuse, and 19.8% reported having used physical force.
      Findings revealed that sexually aggressive women reported significantly higher
      levels of sociosexuality, sexual fantasies of dominance and submission, sexual
      compulsivity, sexual excitation, and sexual inhibition due to the threat of
      sexual performance failure. Data are expected to affect prevention strategies for
      a relevant yet understudied social concern.

PMID- 25854588
TI  - Techniques of Neutralization and Persistent Sexual Abuse by Clergy: A Content
      Analysis of Priest Personnel Files From the Archdiocese of Milwaukee.
AB  - The sexual abuse problem in the Catholic Church has received considerable
      attention by the media in recent years and growing attention from empirical
      researchers. Despite this growth, there is a lack of theoretical research that
      uses neutralization techniques to examine clergy offending. Using Sykes and
      Matza's theory, this study examines the techniques of neutralization used by
      accused priests in the Archdiocese of Milwaukee. Priests' personnel files, which
      were made publicly available by the Archbishop of Milwaukee in July 2013, were
      analyzed retrospectively through a qualitative content analysis of all direct
      statements and correspondences from the accused. The findings indicate that many
      priests denied responsibility or injury in an effort to justify their sexually
      abusive behaviors, but that no discernible patterns of technique use emerged. The
      need for continued research using recently released personnel files from other
      dioceses is also discussed.

PMID- 25854589
TI  - Harmed? Harmful? Experiencing Abusive Adult Children With Mental Disorder Over
      the Life Course.
AB  - Older parents of an adult child coping with a mental disorder that is expressed
      by violent deviant behavior face significant parenting challenges. The purpose of
      this article is to explore the ways older parents exposed to abuse by their adult
      children with mental disorder (ACMD) perceived their child's violent deviant
      behavior along the life course. In a qualitative-phenomenological study, 16
      parents aged 58 to 90 were interviewed in depth. Three major themes emerged: (a)
      ongoing total care for the child's needs along the life course, (b) constructions
      and perceptions of the child through the years-Parents perceived their children
      over two continua, reflecting their experience of the child's deviant behavior:
      the child as more harmed versus more harmful, the child as normative versus
      pathological-and (c) the parent's emotional world toward the harmed-harmful
      child. The findings enable a deeper understanding of the various ways in which
      parents cope with living with deviant behaviors of their ACMD. Hence, this study
      can serve as a framework for developing tailored and differential intervention
      methods.

PMID- 25854591
TI  - Solvent-induced structural transitions of lysozyme in an electrospray ionization
      source.
AB  - The structural characterization of proteins using electrospray ionization mass
      spectrometry (ESI-MS) has become an important method for understanding protein
      structural dynamics. The correlation between the structures of proteins in
      solution and gas phase needs to be understood for the application of ESI-MS to
      protein structural studies. Hen egg white lysozyme (Lyz) is a small protein with
      a stable compact structure in solution. Although it was known that denatured Lyz
      in solution undergoes compaction during transfer into the gas phase via ESI,
      detailed characterization of the process was not available. In the present study,
      we show that the organic cosolvent, which denatures Lyz in solution, induces the
      collapse of the extended Lyz structure into compact structures during ESI. This
      process is further facilitated by the presence of acids, whose conjugate bases
      can interact with Lyz to reduce its charge state and the electrostatic repulsion
      between its charged residues (Analyst, 2015, 140, 661-669). Exposure of ESI
      droplets to acid and solvent vapors confirms that the overall process most
      probably occurs in the charged droplets from ESI. This study provides a detailed
      understanding of the possible influence of the solvent environment on protein
      structure during transfer into the gas phase. 

PMID- 25854592
TI  - On the importance of ferromagnetic exchange between transition metals in field
      free SMMs: examples of ring-shaped hetero-trimetallic [(LnNi2){W(CN)8}]2
      compounds.
AB  - Rare cases of genuine (i.e. field-free) SMM have been found for mixed 3d-4f-5d
      ring-shaped compounds with Tb(III) (Ueff/kB = 23.0 K) or Dy(III) (Ueff/kB = 26.4
      K). The ferromagnetic interactions between the transition metals are shown to
      play an essential role in this feature.

PMID- 25854593
TI  - Myoinositol improves sperm parameters and serum reproductive hormones in patients
      with idiopathic infertility: a prospective double-blind randomized placebo
      controlled study.
AB  - Male infertility is a multifactorial disorder that affects a significant
      percentage of couples. Its etiology and pathogenesis remain elusive in about one
      third of the cases; this is referred to as idiopathic infertility. Inositols
      mediate the sperm processes involved into oocyte fertilization, such as
      penetration of the ovum cumulus oophorus, binding with the zona pellucida and the
      acrosome reaction. The aim of this double-blind, randomized, placebo-controlled
      trial was to evaluate the efficacy and safety of myoinositol (the most abundant
      form of inositols present in nature) treatment in men with idiopathic
      infertility. To accomplish this, we evaluated the effects of myoinositol on sperm
      parameters and reproductive hormones at baseline and after 3 months of treatment
      in men with idiopathic infertility. No adverse reaction was observed. Myoinositol
      significantly increased the percentage of acrosome-reacted spermatozoa, sperm
      concentration, and total count and progressive motility compared to placebo. In
      addition, myoinositol rebalanced serum luteinizing hormone, follicle-stimulating
      hormone, and inhibin B concentrations. The clinical improvement of idiopathic
      infertile patients should encourage myoinositol use for the treatment of this
      disorder, even though its detailed mechanisms at the testicular level remain
      still unclear. 

PMID- 25854595
TI  - That's a good one! Belief in efficacy of mnemonic strategies contributes to age
      related increase in associative memory.
AB  - The development of associative memory during childhood may be influenced by
      metacognitive factors. Here, one aspect of metamemory function--belief in
      strategy efficacy-was tested for a role in the effective use of encoding
      strategies. A sample of 61 children and adults (8-25 years of age) completed an
      associative recognition memory test and were assessed on belief in the efficacy
      of encoding strategies. Independent of age, belief ratings identified two
      factors: "deep" and "shallow" encoding strategies. Although the strategy factor
      structure was stable across age, adolescents and adults were more likely to
      prefer using a deep encoding strategy, whereas children were equally likely to
      prefer a shallow strategy. Belief ratings of deep encoding strategies increased
      with age and, critically, accounted for better associative recognition.

PMID- 25854594
TI  - Is the increased risk of preterm birth following excision for cervical
      intraepithelial neoplasia restricted to the first birth post treatment?
AB  - OBJECTIVE: To explore whether the increased risk of preterm birth following
      treatment for cervical disease is limited to the first birth following
      colposcopy. DESIGN: Nested case-control study. SETTING: Twelve NHS hospitals in
      England. POPULATION: All nonmultiple births from women selected as cases or
      controls from a cohort of women with both colposcopy and a hospital birth. Cases
      had a preterm (20-36 weeks of gestation) birth. Controls had a term birth (38-42
      weeks) and no preterm. METHODS: Obstetric, colposcopy and pathology details were
      obtained. MAIN OUTCOME MEASURES: Adjusted odds ratio of preterm birth in first
      and second or subsequent births following treatment for cervical disease.
      RESULTS: A total of 2798 births (1021 preterm) from 2001 women were included in
      the analysis. The risk of preterm birth increased with increasing depth of
      treatment among first births post treatment [trend per category increase in
      depth, categories <10 mm, 10-14 mm, 15-19 mm, >=20 mm: odds ratio (OR) 1.23, 95%
      confidence interval (95% CI) 1.12-1.36, P < 0.001] and among second and
      subsequent births post treatment (trend OR 1.34, 95% CI 1.15-1.56, P < 0.001). No
      trend was observed among births before colposcopy (OR 0.98, 95% CI 0.83-1.16, P =
      0.855). The absolute risk of a preterm birth following deep treatments (>=15 mm)
      was 6.5% among births before colposcopy, 18.9% among first births and 17.2% among
      second and subsequent births post treatment. Risk of preterm birth (once depth
      was accounted for) did not differ when comparing first births post colposcopy
      with second and subsequent births post colposcopy (adjusted OR 1.15, 95% CI 0.89
      1.49). CONCLUSIONS: The increased risk of preterm birth following treatment for
      cervical disease is not restricted to the first birth post colposcopy; it remains
      for second and subsequent births. These results suggest that once a woman has a
      deep treatment she remains at higher risk of a preterm birth throughout her
      reproductive life.

PMID- 25854596
TI  - Rh(III)- or Ir(III)-catalyzed ynone synthesis from aldehydes via chelation
      assisted C-H bond activation.
AB  - A Rh(III)- or Ir(III)-catalyzed direct aldehyde C-H alkynylation was developed
      for the first time as a simple and practical method for the synthesis of ynones.
      This catalytic reaction proceeds under mild reaction conditions and tolerates a
      variety of synthetically important functional groups (e.g., chloro, bromo,
      aldehyde), thus providing a good complement to previous methods.

PMID- 25854597
TI  - Optimization of EGFR high positive cell isolation procedure by design of
      experiments methodology.
AB  - BACKGROUND: Circulating tumor cells (CTCs) in blood circulation may play a role
      in monitoring and even in early detection of metastasis patients. Due to the
      limited presence of CTCs in blood circulation, viable CTCs isolation technology
      must supply a very high recovery rate. METHODS: Here, we implement design of
      experiments (DOE) methodology in order to optimize the Bio-Ferrography (BF)
      immunomagnetic isolation (IMI) procedure for the EGFR high positive CTCs
      application. All consequent DOE phases such as screening design, optimization
      experiments and validation experiments were used. RESULTS: A significant recovery
      rate of more than 95% was achieved while isolating 100 EGFR high positive CTCs
      from 1 mL human whole blood. CONCLUSIONS: The recovery achievement in this
      research positions BF technology as one of the most efficient IMI technologies,
      which is ready to be challenged with patients' blood samples.

PMID- 25854598
TI  - Morphology and related hemodynamics of the internal carotid arteries of moyamoya
      patients.
AB  - BACKGROUND: Morphological studies investigating the intracranial-extradural
      internal carotid artery with moyamoya disease have not been reported. We designed
      this case-control study to investigate the morphological differences of the
      internal carotid artery with moyamoya disease, and to clarify the contributions
      of these differences to the resultant fluid dynamics. METHODS: Patients with
      moyamoya disease and normal controls were assigned to each group. The vascular
      tortuosity of internal carotid artery was measured with three-dimensional
      rendering using magnetic resonance angiography. By computational fluid dynamics,
      hemodynamic characteristics were simulated and compared between two groups.
      RESULTS: Distances were measured from the carotid canal to the siphon. A shorter
      actual distance was observed in the moyamoya group (p = 0.0170). Vascular
      tortuosity was significantly low in moyamoya patients showing lower curvature
      angles in the petrous and intra-cavernous segments (p = 0.0012). Less blood
      flowed (p < 0.0001) through the narrower internal carotid artery (p < 0.0001) in
      the moyamoya group at the carotid canal level. The blood flow velocities were not
      significantly different (p = 0.2332). Faster blood flow and higher wall shear
      stress in the internal carotid artery bifurcation were verified with
      computational fluid dynamics. CONCLUSIONS: Significant morphological differences
      were confirmed to exist in the intracranial-extradural internal carotid artery of
      moyamoya patients. These differences might influence the hemodynamics around the
      bifurcation of the internal carotid artery.

PMID- 25854599
TI  - Does fluorescein sodium-guided resection of cerebral metastases increase rates of
      total resections?

PMID- 25854600
TI  - Intraoperative cerebral angiosonography with ultrasound contrast agents: how I do
      it.
AB  - BACKGROUND: Intraoperative vessel visualization is highly desirable, especially
      when the target is related to or close to main vessels, such as in the skull base
      and vascular surgery. Contrast-enhanced ultrasound (CEUS) is an imaging technique
      that allows visualization of tissue perfusion and vascularization through the
      infusion of purely intravascular ultrasound contrast agents (UCA). METHODS: After
      cerebral scanning with B-mode ultrasound (US) CEUS is performed, UCA are injected
      and insonated with low mechanical index US. A UCA-specific harmonic signal is
      transduced using a contrast-specific algorithm to obtain real-time
      angiosonography (ASG). CONCLUSIONS: Real-time intraoperative ASG is a rapid,
      reliable, repeatable method for vessel visualization and evaluation of tissue
      perfusion.

PMID- 25854601
TI  - Functional co-expression of a fungal ferulic acid esterase and a beta-1,4
      endoxylanase in Festuca arundinacea (tall fescue) modifies post-harvest cell wall
      deconstruction.
AB  - MAIN CONCLUSION: Improved post-harvest cell wall deconstruction of tall fescue
      leaves has been demonstrated by in-planta co-expression of a constitutively
      expressed ferulic acid esterase together with a senescence-induced beta-1,4
      endoxylanase. Tall fescue plants (Festuca arundinacea) constitutively expressing
      vacuole- or apoplast-targeted ferulic acid esterase from Aspergillus niger were
      retransformed with a senescence-induced and apoplast-targeted beta-1,4 endo
      xylanase from Trichoderma reesei. Enzyme activities in co-expressing plants
      stabilized after repeated vegetative propagation, with xylanase activity in
      senescent leaves increasing and ferulic acid esterase activity decreasing after
      tillering. Plants co-expressing both enzymes in the apoplast, with the lowest
      levels of ferulate monomers and dimers and the lowest levels of cell wall
      arabinoxylans, released ten times more cell wall hydroxycinnamic acids and five
      times more arabinoxylan from the cell wall on autodigestion compared to
      expression of ferulic acid esterase or xylanase alone. These plants also showed a
      31 % increase in cellulase-mediated release of reducing sugars, a 5 % point
      increase in in vitro dry matter digestibility and a 23 % increase in acetyl
      bromide-soluble lignin. However, plant growth was adversely affected by
      expressing FAE in the apoplast, giving plants with narrower shorted leaves, and a
      71 % decrease in biomass.

PMID- 25854602
TI  - Biochemical characterization of caffeoyl coenzyme A 3-O-methyltransferase from
      wheat.
AB  - MAIN CONCLUSION: TaCCoAOMT1 is located in wheat chromosome 7A and highly
      expressed in stem and root. It is important for lignin biosynthesis, and
      associated with stem maturity but not lodging resistance. Caffeoyl coenzyme A 3-O
      methyltransferases (CCoAOMTs) are one important class of enzymes to carry out the
      transfer of the methyl group from S-adenosylmethionine to the hydroxyl group, and
      play important roles in lignin and flavonoids biosynthesis. In the present study,
      sequences for CCoAOMT from the wheat genome were analyzed. One wheat CCoAOMT that
      belonged to bona fide subclade involved in lignin biosynthesis, namely
      TaCCoAOMT1, was obtained by the prokaryotic expression in E. coli. The three
      dimensional structure prediction showed a highly similar structure of TaCCoAOMT1
      with MsCCoAOMT. Recombinant TaCCoAOMT1 protein could only use caffeoyl CoA and 5
      hydroxyferuloyl CoA as effective substrates and caffeoyl CoA as the best
      substrate. TaCCoAOMT1 had a narrow optimal pH and thermal stability. The
      TaCCoAOMT1 gene was highly expressed in wheat stem and root tissues, paralleled
      CCoAOMT enzyme activity. TaCCoAOMT1 mRNA abundance and enzyme activity increased
      linearly with stem maturity, but showed little difference between wheat lodging
      resistant (H4546) and lodging-sensitive (C6001) cultivars in elongation, heading
      and milky stages. These data suggest that TaCCoAOMT1 is an important CCoAOMT for
      lignin biosynthesis that is critical for stem development, but not directly
      associated with lodging-resistant trait in wheat.

PMID- 25854603
TI  - Expression platforms for producing eukaryotic proteins: a comparison of E. coli
      cell-based and wheat germ cell-free synthesis, affinity and solubility tags, and
      cloning strategies.
AB  - Vectors designed for protein production in Escherichia coli and by wheat germ
      cell-free translation were tested using 21 well-characterized eukaryotic proteins
      chosen to serve as controls within the context of a structural genomics pipeline.
      The controls were carried through cloning, small-scale expression trials, large
      scale growth or synthesis, and purification. Successfully purified proteins were
      also subjected to either crystallization trials or (1)H-(15)N HSQC NMR analyses.
      Experiments evaluated: (1) the relative efficacy of restriction/ligation and
      recombinational cloning systems; (2) the value of maltose-binding protein (MBP)
      as a solubility enhancement tag; (3) the consequences of in vivo proteolysis of
      the MBP fusion as an alternative to post-purification proteolysis; (4) the effect
      of the level of LacI repressor on the yields of protein obtained from E. coli
      using autoinduction; (5) the consequences of removing the His tag from proteins
      produced by the cell-free system; and (6) the comparative performance of E. coli
      cells or wheat germ cell-free translation. Optimal promoter/repressor and fusion
      tag configurations for each expression system are discussed. 

PMID- 25854604
TI  - Establishment of a total liquid ventilation system using saline-based oxygen
      micro/nano-bubble dispersions in rats.
AB  - Micro/nano-bubbles are practical nanomaterials designed to increase the gas
      content in liquids. We attempted to use oxygen micro/nano-bubble dispersions as
      an oxygen-rich liquid as a means for total liquid ventilation. To determine the
      oxygen content in the bubble dispersion, a new method based on a
      spectrophotometric change between oxy- and deoxy-hemoglobin was established. The
      oxygen micro/nano-bubble dispersion was supplied to an experimental total
      ventilation liquid in anesthetic rats. Though the amount of dissolving oxygen was
      as low as 6 mg/L in physiological saline, the oxygen content in the oxygen
      micro/nano-bubble dispersion was increased to 45 mg/L. The positive correlation
      between the oxygen content and the life-saving time under liquid ventilation
      clearly indicates that the life-saving time is prolonged by increasing the oxygen
      content in the oxygen micro/nano-bubble dispersion. This is the first report
      indicating that the oxygen micro/nano-bubbles containing a sufficient amount of
      oxygen are useful in producing oxygen-rich liquid for the process of liquid
      ventilation. 

PMID- 25854605
TI  - Suspected cold agglutination during mild hypothermic pediatric open heart
      surgery: a report of two cases.
AB  - Cold agglutination was suspected in 2 pediatric open heart surgery cases during
      mild hypothermic cardiopulmonary bypass. The first patient was a 2-year-old boy
      with secundum atrial septal defect. Fifteen minutes after the initiation of mild
      hypothermic cardiopulmonary bypass, the inlet pressure of oxygenator suddenly
      elevated from 250 to over 500 mmHg, whereas outlet pressure was maintained. The
      blood flow rate decreased from 140 to 85 ml/kg/min. At that time, the arterial
      blood temperature was less than 32 degrees C. Cold agglutinin was highly
      suspected, so patient was immediately warmed, and the inlet pressure of
      oxygenator decreased to 250 mmHg when the arterial blood temperature reached to
      36 degrees C. Second patient was a 3-year-old boy with secondary developed
      subvalvular pulmonary stenosis after the repair of double chambered right
      ventricle at 10 months of his age. Eighteen minutes after the initiation of mild
      hypothermic cardiopulmonary bypass, the inflow pressure suddenly elevated to 500
      mmHg and transmission flow decreased to 55 ml/kg/min. Twenty-three minutes after
      warming, the pressure fell to a normal level and transmission flow was recovered.
      The operation continued with normo-thermic cardiopulmonary bypass and crystalloid
      cardioplegia. Both cases had no postoperative complications related to cold
      agglutinin such as myocardial infarction, cerebral infarction, or renal
      insufficiency.

PMID- 25854606
TI  - Acclimatization of the gait pattern to wearing an ankle-foot orthosis in children
      with spastic cerebral palsy.
AB  - BACKGROUND: Ankle-foot orthoses can be prescribed to improve gait in children
      with cerebral palsy. Before evaluating the effects of ankle-foot orthoses on
      gait, a period to adapt or acclimatize is usually applied. It is however unknown
      whether an acclimatization period is actually needed to reliably evaluate the
      effect of a new orthosis on gait. This study aimed to investigate whether
      specific gait parameters in children with cerebral palsy would change within an
      acclimatization period after being provided with new ankle-foot orthoses.
      METHODS: Ten children with cerebral palsy, walking with excessive knee flexion in
      midstance (8 boys; mean (SD) 10.2 (1.9) years; Gross Motor Function
      Classification System levels I-II) were provided with ventral shell ankle-foot
      orthoses. The orthoses were worn in combination with the child's own shoes and
      tuned, based on ground reaction force alignment with respect to the lower limb
      joints. Directly after tuning (T0) and four weeks later (T1), 3D-gait analysis
      was performed using an optoelectronic motion capture system and a force plate.
      From this assessment, ten spatiotemporal, kinematic and kinetic gait parameters
      were derived for the most affected leg. Differences in parameters between T0 and
      T1 were analyzed using paired t-tests or Wilcoxon signed rank tests (P<0.05).
      FINDINGS: Over the course of four weeks, no significant differences (P >= 0.080)
      were observed for any investigated parameter. INTERPRETATION: These results imply
      that the biomechanical effect of ventral shell ankle-foot orthoses on gait in
      independent walking children with cerebral palsy is immediately apparent, i.e.,
      there is no further change after acclimatization.

PMID- 25854607
TI  - How exciton-vibrational coherences control charge separation in the photosystem
      II reaction center.
AB  - In photosynthesis absorbed sun light produces collective excitations (excitons)
      that form a coherent superposition of electronic and vibrational states of the
      individual pigments. Two-dimensional (2D) electronic spectroscopy allows a
      visualization of how these coherences are involved in the primary processes of
      energy and charge transfer. Based on quantitative modeling we identify the
      exciton-vibrational coherences observed in 2D photon echo of the photosystem II
      reaction center (PSII-RC). We find that the vibrations resonant with the exciton
      splittings can modify the delocalization of the exciton states and produce
      additional states, thus promoting directed energy transfer and allowing a switch
      between the two charge separation pathways. We conclude that the coincidence of
      the frequencies of the most intense vibrations with the splittings within the
      manifold of exciton and charge-transfer states in the PSII-RC is not occurring by
      chance, but reflects a fundamental principle of how energy conversion in
      photosynthesis was optimized. 

PMID- 25854608
TI  - Fabrication of liquid-infused surfaces using reactive polymer multilayers:
      principles for manipulating the behaviors and mobilities of aqueous fluids on
      slippery liquid interfaces.
AB  - The design of slippery liquid-infused porous surfaces (SLIPS) using nanoporous
      and chemically reactive polymer multilayers is reported. This approach permits
      fabrication of slippery anti-fouling coatings on complex surfaces and provides
      new means to manipulate the mobilities of contacting aqueous fluids. The results
      expand the range of tools that can be used to manipulate the behaviors of SLIPS
      and open the door to new applications of this emerging class of soft materials. 

PMID- 25854609
TI  - Spectroscopic (FT-IR/FT-Raman) and computational (HF/DFT) investigation and
      HOMO/LUMO/MEP analysis on 1,1-difluoro-2-vinyl-cyclopropane.
AB  - All the computational calculations were made in the ground state using the HF and
      DFT (B3LYP) methods with 6-31++G (d,p) and 6-311++G (d,p) basis sets. Making use
      of the recorded data, the complete vibrational assignments were made and analysis
      of the observed fundamental bands of molecule was carried out. The shifting of
      the frequencies in the vibrational pattern of the title molecule due to the
      substitutions; CHCH2 and F were deeply investigated by the vibrational analysis.
      Moreover, (13)C NMR and (1)H NMR chemical shifts were calculated by using the
      gauge independent atomic orbital (GIAO) method with HF/B3LYP methods with 6
      311++G (d,p). A study on the electronic properties, such as HOMO and LUMO
      energies, were performed by time-dependent DFT (TD-DFT) approach. Mulliken
      charges of the 1DF2VCP were also calculated and interpreted. The thermodynamic
      properties (heat capacity, entropy, and enthalpy) of the title compound at
      different temperatures were calculated in gas phase.

PMID- 25854610
TI  - A vibrational spectroscopy study on 3-aminophenylacetic acid by DFT calculations.
AB  - In this study, in which the group vibrations of 3-aminophenylacetic acid were
      investigated by electronic structure calculations based on Density Functional
      Theory (DFT), the possible stable conformers of the molecule were searched
      through a relaxed "potential energy surface scan" carried out at B3LYP/6-31G(d)
      level of theory. The corresponding equilibrium geometrical and vibrational
      spectral data for each of the determined stable conformers and for their possible
      dimer structures were obtained through "geometry optimisation" and "frequency"
      calculations carried out at B3LYP/6-31G(d) and B3LYP/6-311G++(d,p) levels of
      theory. The obtained results confirmed that anharmonic wavenumbers calculated at
      B3LYP/6-311G++(d,p) level generally quite well agree with the experimental
      wavenumbers, however, harmonic wavenumbers calculated at both levels of theory
      need an efficient refinement for a satisfactory agreement with experiment. In
      particular, the harmonic wavenumbers, IR and Raman intensities refined within
      Scaled Quantum Mechanical Force Field (SQM FF) methodology constituted the
      primary data set in the interpretation of the experimental FT-IR, FT-Raman and
      dispersive Raman spectra of 3-aminophenylacetic acid. By the help of these
      refined spectral data, the effects of conformation and intermolecular hydrogen
      bonding on the fundamental bands observed in the experimental spectra could be
      correctly predicted. 

PMID- 25854611
TI  - Study of acoustic fingerprinting of nitromethane and some triazole derivatives
      using UV 266 nm pulsed photoacoustic pyrolysis technique.
AB  - We report a comparative study of acoustic fingerprints of nitromethane,
      nitrobenzene and some nitro rich triazole derivatives using pulsed photoacoustic
      technique. UV 266 nm wavelength i.e. Fourth harmonic of Q-switched Nd: YAG laser
      having pulse duration 7 ns and 10 Hz repetition rate is employed to record the
      time resolved PA spectrum. The PA fingerprint is produced due to absorption of
      incident UV light by molecule itself and photo dissociation of nitromethane and
      nitrobenzene at room temperature while in case of triazole it is attributed to
      the combination of thermal and photo-dissociation process. The entire
      dissociation process follows the root of cleavage of C-NO2 bond to produce free
      NO, NO2 and other by product gases due to pi(*)<-n excitation. In addition, we
      have studied the thermal stability criteria of nitro rich triazoles based on the
      quality factor of acoustic resonance frequencies of the PA cavity. We have also
      studied the effect of data acquisition time to ascertain the decay behavior of
      HEMs samples.

PMID- 25854612
TI  - CRIT-LINE: a noninvasive tool to monitor hemoglobin levels in pediatric
      hemodialysis patients.
AB  - BACKGROUND: The national average for achieving the KDOQI-recommended hemoglobin
      (Hgb) target level of 11-12 g/dL is low with the current anemia management
      protocol of measuring Hgb levels every 2-4 weeks to guide intervention. The
      objective of this study was to correlate initial Hgb readings from the CRIT-LINE
      monitor with actual serum Hgb levels in pediatric patients on hemodialysis (HD).
      METHODS: Data were collected from pediatric HD patients who had Hgb tests ordered
      for routine and/or clinical reasons. Hgb concentrations were read with the CRIT
      LINE after 0.5 or 1 L of blood had been processed by HD in patients with a body
      weight of <=20 or >20 kg, respectively. Ultrafiltration was kept at a minimum
      until the CRIT-LINE Hgb was read. RESULTS: In total, 217 Hgb readings from 23 HD
      patients were analyzed. Results showed a statistically significant correlation
      between CRIT-LINE readings and laboratory Hgb measurements (r = 0.94, p < 0.0001)
      using Pearson correlation coefficients for well-distributed data. The mean Hgb
      levels measured by CRIT-LINE and the laboratory were 11.12 +/- 1.63 and 11.31 +/-
      1.69 g/dL, respectively. CONCLUSIONS: The CRIT-LINE monitor is an accurate
      instrument for monitoring Hgb levels in HD patients. Further studies will be
      needed to evaluate whether using CRIT-LINE Hgb levels to guide anemia management
      will improve the percentage of children with Hgb levels within target.

PMID- 25854613
TI  - Estimation of glomerular filtration rate with and without height: effect of age
      and renal function level.
AB  - BACKGROUND: The current glomerular filtration rate (GFR) equation (CKiD) may be
      less accurate in adolescents and children with higher GFR. METHODS: This was a
      retrospective study (n = 161, 247 (99)mTc DTPA-GFRs). Six equations were
      evaluated for bias, accuracy, and low GFR diagnosis: (1) CKiD; (2) historic
      center; (3) Hoste(age); (4) Hoste(height); (5) modified Pottel; (6) Gao. Children
      with >= vs. <90 ml/min/1.73 m(2)) and < vs. >=16 years were compared. Two adult
      equations were evaluated in children >=16 years. RESULTS: Most equations
      underestimated GFR by 1-14 % in the higher GFR group, least so for Hoste(age). In
      the low GFR group, Hoste(age) and historic center overestimated GFR significantly
      more than CKiD (p < 0.05). Accuracy (within 30 % GFR) was similar across
      equations and GFR subgroups (66-86 %). In the >=16 years group, CKiD
      underestimated GFR by ~10 %, vs. ~3 % for Hoste(height). Accuracy was 5-10 %
      lower in the older group and most equations were more sensitive than specific for
      detecting low GFR; this discrepancy was less for the Hoste equations. Adult
      equations were highly inaccurate. CONCLUSIONS: GFR estimation in older children
      and with higher GFR is suboptimal. The Hoste(height) may be an alternative GFR
      estimation method; Hoste(age) may allow for height-independent GFR estimation in
      patients with normal GFR.

PMID- 25854614
TI  - Using mixed methods to identify and answer clinically relevant research
      questions.
AB  - The need for mixed methods research in answering health care questions is
      becoming increasingly recognized because of the complexity of factors that affect
      health outcomes. In this article, we argue for the value of using a qualitatively
      driven mixed method approach for identifying and answering clinically relevant
      research questions. This argument is illustrated by findings from a study on the
      self-management practices of cancer survivors and the exploration of one
      particular clinically relevant finding about higher uptake of self-management in
      cancer survivors who had received chemotherapy treatment compared with those who
      have not. A cross-sectional study generated findings that formed the basis for
      the qualitative study, by informing the purposive sampling strategy and
      generating new qualitative research questions. Using a quantitative research
      component to supplement a qualitative study can enhance the generalizability and
      clinical relevance of the findings and produce detailed, contextualized, and rich
      answers to research questions that would be unachievable through quantitative or
      qualitative methods alone. 

PMID- 25854615
TI  - Barriers to Male Involvement in Antenatal Care in Rural Mozambique.
AB  - Low rates of antenatal care (ANC) service uptake limit the potential impact of
      mother-to-child HIV-prevention strategies. Zambezia province, Mozambique, has one
      of the lowest proportions of ANC uptake among pregnant women in the country,
      despite the availability of free services. We sought to identify factors
      influencing ANC service uptake (including HIV counseling and testing) through
      qualitative methods. In addition, we encouraged discussion about strategies to
      improve uptake of services. We conducted 14 focus groups to explore community
      views on these topics. Based on thematic coding of discourse, two main themes
      emerged: (a) gender inequality in decision making and responsibility for
      pregnancy and (b) community beliefs that uptake of ANC services, particularly, if
      supported by a male partner, reflects a woman's HIV-positive status.
      Interventions to promote ANC uptake must work to shift cultural norms through
      male partner participation. Potential strategies to promote male engagement in
      ANC services are discussed. 

PMID- 25854616
TI  - Perceptions of health professionals on pain in extremely low gestational age
      infants.
AB  - Extremely low gestational age infants (<28 weeks at birth) experience significant
      pain from repeated therapeutic procedures while hospitalized in the neonatal
      intensive care unit. As part of a program of research examining pain in preterm
      infants, we conducted a qualitatively driven mixed-methods design, supplemented
      with a qualitative and quantitative component, to understand how health care
      professionals (HCPs) assess and manage procedural pain for tiny and
      underdeveloped preterm infants. Fifty-nine HCPs from different disciplines across
      four tertiary-level neonatal units in Canada participated in individual or focus
      group interviews and completed a brief questionnaire. Four themes from the
      content analysis were (a) subtlety and unpredictability of pain indicators, (b)
      infant and caregiver attributes and contextual factors that influence pain
      response and practices, (c) the complex nature of pain assessment, and (d)
      uncertainty in the management of pain. The information gleaned from this study
      can assist in identifying gaps in knowledge and informing unit-based and
      organizational knowledge translation strategies for this vulnerable population. 

PMID- 25854617
TI  - Inside the "Black Box" of a Knowledge Translation Program in Applied Health
      Research.
AB  - In this article, we present the findings of a participatory realistic evaluation
      of a 5-year program of health care research intended to promote the translation
      of knowledge into routine clinical practice. The program was one of the nine
      pilot Collaborations for Leadership in Applied Health Research and Care funded by
      the English National Institute for Health Research between 2008 and 2013. Our aim
      was to delineate the mechanisms by which, and circumstances in which, some
      projects carried out under the program achieved success in knowledge translation
      while others were frustrated. Using qualitative methods, we examined how closer
      collaboration between academics and clinicians worked in four purposefully chosen
      case studies. In a synthesis of the findings, we produced a "black box" model of
      how knowledge translation was enabled by the activation of nine mechanisms. These
      are summarized in the form of five simple rules for promoting knowledge
      translation through collaborations based on principles of coproduction. 

PMID- 25854618
TI  - Nontraumatic Descemet Membrane Detachment with Tear in Osteogenesis Imperfecta.
AB  - We report the first case of unilateral spontaneous Descemet membrane detachment
      (DMD) with tear occurring in a patient with osteogenesis imperfecta (OI). A 20
      year-old male patient with OI presented with a history of recent primary repair
      (2 weeks prior) of left globe rupture following local finger trauma to the left
      eye. The patient had no history of other ocular surgery or trauma. The
      examination revealed a best corrected visual acuity of 20/40 in the right and no
      light perception in the left eye. Slit-lamp examination showed an oval giant
      Descemet tear extending from the 12 o'clock to the 5 o'clock area and a large DMD
      involving the upper and nasal quadrants in the right cornea. It was thought that
      monitoring the patient without intervention and only considering a surgical
      procedure if the disorder progressed was the best option, taking into account the
      patient's reasonable visual acuity and the risks of keratoplasty. The dimensions
      of the DMD and tear had remained the same at 1-year follow-up period. We believe
      that follow-up without intervention should be considered for non-progressive DMD
      with a giant tear if the patient has a single functional eye. 

PMID- 25854619
TI  - Quantitative analysis of 31P NMR spectra of soil extracts--dealing with overlap
      of broad and sharp signals.
AB  - Solution (31)P NMR analysis following extraction with a mixture of sodium
      hydroxide and ethylenediaminetetraacetic acid is the most widely used method for
      detailed characterization of soil organic P. However, quantitative analysis of
      the (31)P NMR spectra is complicated by severe spectral overlap in the monoester
      region. Various deconvolution procedures have been developed for the task, yet
      none of these are widely accepted or implemented. In this mini-review, we first
      describe and compare these varying approaches. We then review approaches to
      similar issues of spectral overlap in biomedical science applications including
      NMR-based metabolic profiling and analyzing (31)P magnetic resonance spectra of
      ex vivo and in vivo intact tissues. The greater maturity and resourcing of this
      biomedical research means that a wider variety of approaches has been developed.
      Of particular relevance are approaches to dealing with overlap of broad and sharp
      signals. Although the existence of this problem is still debated in the context
      of soil analyses, not only is it well-recognized in biomedical applications, but
      multiple approaches have been developed to deal with it, including T2 editing and
      time-domain fitting. Perhaps the most transferable concept is the incorporation
      of 'prior knowledge' in the fitting of spectra. This is well established in
      biomedical applications but barely touched in soil analyses. We argue that
      shortcuts to dealing with overlap in the monoester region (31)P NMR soil spectra
      are likely to be found in the biomedical literature, although some degree of
      adaptation will be necessary.

PMID- 25854620
TI  - A hybrid ruthenium alkynyl/zinc porphyrin "Cross Fourchee" with large cubic NLO
      properties.
AB  - A new Zn(ii) porphyrin-cored ruthenium alkynyl dendrimer (2) containing twelve
      Ru(kappa(2)-dppe)2 bis-alkynyl fragments has been prepared in two steps from
      5,10,15,20-tetra(4-ethynylphenyl)porphyrinatozinc(ii) and shown to be highly
      active for third-harmonic generation (THG) at 1907 nm. 

PMID- 25854621
TI  - Left atrial electrophysiologic feature specific for the genesis of complex
      fractionated atrial electrogram during atrial fibrillation.
AB  - Complex fractionated atrial electrogram (CFAE) has been suggested to contribute
      to the maintenance of atrial fibrillation (AF). However, electrophysiologic
      characteristics of the left atrial myocardium responsible for genesis of CFAE
      have not been clarified. Non-contact mapping of the left atrium was performed at
      37 AF onset episodes in 24 AF patients. Electrogram amplitude, width, and
      conduction velocity were measured during sinus rhythm, premature atrial
      contraction (PAC) with long- (L-PAC), short- (S-PAC) and very short-coupling
      intervals (VS-PAC). These parameters were compared between CFAE and non-CFAE
      regions. Unipolar electrogram amplitude was higher in CFAE than non-CFAE during
      sinus rhythm, L-, S- and VS-PAC (1.82 +/- 0.73 vs. 1.13 +/- 0.38, p < 0.001; 1.44
      +/- 0.54 vs. 0.92 +/- 0.35, p < 0.001; 1.09 +/- 0.40 vs. 0.70 +/- 0.27, p <
      0.001; 0.76 +/- 0.30 vs. 0.53 +/- 0.25 mV, p < 0.001). Laplacian bipolar
      electrogram amplitude was also higher in CFAE than non-CFAE during sinus rhythm,
      L-, S- and VS-PAC. Unipolar electrogram width was similar in CFAE and non-CFAE.
      Laplacian bipolar electrogram width was wider in CFAE than non-CFAE during L-, S-
      and VS-PAC (85.5 +/- 6.8 vs. 79.6 +/- 4.5, p < 0.001; 96.1 +/- 9.7 vs. 84.5 +/-
      5.9, p < 0.001; 122.4 +/- 16.0 vs. 99.6 +/- 9.6 ms, p < 0.001), but not during
      sinus rhythm. The conduction velocity was slower in CFAE during sinus rhythm, L-,
      S- and VS-PAC than non-CFAE (1.7 +/- 0.3 vs. 2.4 +/- 0.4, p < 0.001; 1.4 +/- 0.3
      vs. 2.0 +/- 0.5, p < 0.001; 1.2 +/- 0.3 vs. 1.7 +/- 0.5, p < 0.001; and 0.9 +/-
      0.3 vs. 1.4 +/- 0.4 m/s, p < 0.001). CFAE was generated in the high amplitude
      atrial myocardium with slow and non-uniform conduction properties which were
      pronounced associated with premature activation, suggesting that heterogeneous
      conduction produced in high amplitude region contributes to the genesis of CFAE. 

PMID- 25854623
TI  - Noninvasive discrimination between human normal and cancer cells by analysis of
      intracellular distribution of phase-shift data.
AB  - Aiming to establish a method for the noninvasive discrimination of cancer cells
      from normal cells in adherent culture, we investigated to employ all phase shift
      data for all pixels inside a cell. The bird's-eye views of phase shifts of human
      prostate epithelial cells (PRECs) and human prostatic carcinoma epithelial cell
      (PC-3) lines acquired by phase-shifting laser microscopy showed tableland and
      cone shapes, respectively, while treatment of PRECs with cytochalasin D resulted
      in the cone shape. So, the profile of phase shift in both sections towards the x-
      and y-axes of the views through the peaks of the phase shifts in PRECs and PC-3
      cells were trapezoid-like and triangle-like, respectively. Typical profiles of
      phase shifts in a section in PRECs or PC-3 cells were calculated by averaging
      from 10 cells and smoothing. Cancer index is defined as the deduction of sums of
      the squared difference between a real cell and the typical profiles for a PREC
      and a PC-3 cell. The cancer indices for PC-3 and hepatocellular carcinoma cell
      lines were positive, while those for PRECs and human normal cryopreserved
      hepatocytes were negative. Cancer indices along the major axis of fibroblast-like
      cells of normal mesenchymal stem cells and the osteosarcoma cell line were
      negative and positive, respectively. Consequently, several cancer cells could be
      noninvasively discriminated from normal cells by calculating the cancer index
      employing phase shift for all pixels inside the cells. 

PMID- 25854622
TI  - Bilateral internal thoracic artery grafting in octogenarians: where are the
      benefits?
AB  - The use of bilateral internal thoracic artery (BITA) grafting for myocardial
      revascularization is usually discouraged in the very elderly because of increased
      risk of perioperative complications. The aim of the study was to analyze early
      and late outcomes of BITA grafting in octogenarians. From January 1999 throughout
      February 2014, 236 consecutive octogenarians with multivessel coronary artery
      disease underwent primary isolated coronary bypass surgery at the authors'
      institution. Six of these patients underwent emergency surgery and were excluded
      from this retrospective study; consequently, 135 BITA patients were compared with
      95 single internal thoracic artery (SITA) patients according to early and late
      outcomes. Between BITA and SITA patients, there was no significant difference in
      the operative risk (EuroSCORE II: 8 +/- 7.7 vs. 7.6 +/- 6.1 %, p = 0.65). There
      was a lower aortic manipulation in BITA patients. Hospital mortality (3 vs. 4.2
      %, p = 0.44) and perioperative complications were similar except that only BITA
      patients experienced sternal wound infection (5.2 %, p = 0.022). The mean follow
      up was 4.7 +/- 3.3 years. There were no differences between the two groups in
      overall survival (p = 0.79), freedom from cardiac and cerebrovascular deaths (p =
      0.73), major adverse cardiac and cerebrovascular events (p = 0.63) and heart
      failure hospital readmission (p = 0.64). Predictors of decreased late survival
      were diabetes (p = 0.0062) and congestive heart failure (p = 0.0004). BITA
      grafting can be routinely used in octogenarians with atherosclerotic ascending
      aorta without an increase in hospital mortality or major adverse cardiac and
      cerebrovascular complications. However, there is an increased risk of sternal
      wound infection without a demonstrable long-term benefit. 

PMID- 25854624
TI  - Switching from current factor VIII (FVIII) to longer acting FVIII concentrates-
      what is the real potential benefit?

PMID- 25854625
TI  - Extractability and chromatographic characterization of wheat (triticum aestivum
      l.) bran protein.
AB  - About 70% of the protein for human consumption is derived from plants, with
      cereals as the most important source. Wheat bran protein has a more balanced
      amino acid profile than that of flour. We here for the first time report the
      amino acid, size exclusion, and SDS-PAGE profiles of bran Osborne protein
      fractions (OPFs). Moreover, we also investigated how OPFs are affected when
      physical barriers which entrap proteins in bran tissues are removed.
      Albumin/globulin is the most abundant OPF. It is richer in lysine and
      asparagine/aspartic acid than other OPF. Most bran albumin/globulin proteins have
      a molecular weight (MW) lower than 30 k and their chromatographic profiles differ
      from those of flour. The prolamin has high levels of proline and
      glutamine/glutamic acid. It is rich in proteins with a MW of 30 to 45 k and about
      66 k reflecting contamination with gliadin from endosperm. The glutelin has high
      levels of glycine, proline, and glutamine/glutamic acid. Its protein is of
      intermediate and high MW with little protein with MW lower than 30 k. The high
      (MWs from 80 to 120 k) and low (MW around 45 k) MW glutenin subunits of flour are
      also present in bran. The glutelin of wheat endosperm is named glutenin. Ball
      milling releases albumin/globulin and glutelin but not prolamin. Not all glutelin
      was endosperm glutenin as a substantial part was entrapped in the aleurone cells.

PMID- 25854626
TI  - Response, use and habituation to a mouse house in C57BL/6J and BALB/c mice.
AB  - Animal welfare depends on the possibility to express species-specific behaviours
      and can be strongly compromised in socially and environmentally deprived
      conditions. Nesting materials and refuges are very important resources to express
      these behaviours and should be considered as housing supplementation items. We
      evaluated the effects of one item of housing supplementation in standard settings
      in laboratory mice. C57BL/6JOlaHsd (B6) and BALB/cOlaHsd (BALB) young male and
      female mice, upon arrival, were housed in groups of four in standard laboratory
      cages and after 10 days of acclimatization, a red transparent plastic triangular
      shaped Mouse HouseTM was introduced into half of the home cages. Animals with or
      without a mouse house were observed in various contexts for more than one month.
      Body weight gain and food intake, home cage behaviours, emotionality and response
      to standard cage changing procedures were evaluated. The presence of a mouse
      house in the home cage did not interfere with main developmental and behavioural
      parameters or emotionality of BALB and B6 male and female mice compared with
      controls. Both strains habituated to the mouse house in about a week, but made
      use of it differently, with BALB mice using the house more than the B6 strain.
      Our results suggest that mice habituated to the mouse house rather quickly
      without disrupting their home cage activities. Scientists can thus be encouraged
      to use mouse houses, also in view of the implementation of the EU Directive
      (2010/63/EU). 

PMID- 25854627
TI  - The dynamics of adult haematopoiesis in the bone and bone marrow environment.
AB  - This review explores the dynamic relationship between bone and bone marrow in the
      genesis and regulation of adult haematopoiesis and will provide an overview of
      the haematopoietic hierarchical system. This will include the haematopoietic stem
      cell (HSC) and its niches, as well as discuss emerging evidence of the reciprocal
      interplay between bone and bone marrow, and support of the pleiotropic role
      played by bone cells in the regulation of HSC proliferation, differentiation and
      function. In addition, this review will present demineralized bone matrix as a
      unique acellular matrix platform that permits the generation of ectopic de novo
      bone and bone marrow and provides a means of investigating the temporal sequence
      of bone and bone marrow regeneration. It is anticipated that the utilization of
      this matrix-based approach will help researchers in gaining deeper insights into
      the major events leading to adult haematopoiesis in the bone marrow. Furthermore,
      this model may potentially offer new avenues to manipulate the HSC niche and
      hence influence the functional output of the haematopoietic system. 

PMID- 25854628
TI  - Timing of thrombolysis for acute ischaemic stroke: the earlier the treatment the
      better the outcome, irrespective of age or stroke severity.

PMID- 25854629
TI  - Editorial Comment from Dr Wu to Sulfoquinovosylacylpropanediol is a novel potent
      radiosensitizer in prostate cancer.

PMID- 25854630
TI  - Augmentation of water-holding and textural properties of breast meat from
      oxidatively stressed broilers by dietary antioxidant regimens.
AB  - 1. The impact of dietary antioxidants and degree of oil oxidation on textural
      attributes of chicken broiler breast meat stored in oxygen-enriched, air
      permeable polyvinylchloride and skin packaging systems during retail display at 2
      4 degrees C for up to 21 d was assessed. 2. Broilers were fed on diets either
      with a low-oxidised oil (peroxide 23 mEq O2/kg) or with a high-oxidised oil
      (peroxide 121 mEq O2/kg), with or without an algae-based antioxidant and organic
      mineral antioxidant supplement for 42 d. 3. Fatty acids and radical scavenging
      activities of the diets were estimated. Meat colour, pH, myofibrillar protein
      profile and textural traits were measured. 4. Diets with high-oxidised oil
      reduced stearic, linoleic and linolenic acid content compared to low-oxidised oil
      samples, regardless of antioxidant supplementation. Meat colour and pH varied
      among dietary treatments throughout storage. Meat samples from the antioxidant
      dietary group, irrespective of oil oxidation level, had lower amounts of purge
      and cooking losses compared to the unsupplemented diets. For all packaging
      systems, meat shear force was significantly higher for broilers fed on high
      oxidised diets. 5. The results demonstrate that dietary antioxidant
      supplementation can minimise the negative impact of oxidised oil on the quality
      of broiler meat packaged in different atmospheric environments. 

PMID- 25854631
TI  - Transfusion-associated dyspnea--shadow or substance?
AB  - New Zealand Blood Service Haemovigilance uses International Society of Blood
      Transfusion/International Haemovigilance Network definitions to categorize
      transfusion reactions (TR). Transfusion-associated dyspnoea (TAD) is a category
      for TR with respiratory features (TRRF) that do not fit definitive entities.
      TRRF, including TAD, are clinically significant. TR classified as TAD were
      reviewed. We found that many TAD may have been transfusion-associated circulatory
      overload. Better information in TR reports and refining TR diagnostic criteria
      may result in less misclassification of TRRF. TAD may represent mild, atypical or
      overlap entities, and there may be a residuum of cases with currently unexplained
      pathophysiology. 

PMID- 25854632
TI  - Instability restricts signaling of multiple fibroblast growth factors.
AB  - Fibroblast growth factors (FGFs) deliver extracellular signals that govern many
      developmental and regenerative processes, but the mechanisms regulating FGF
      signaling remain incompletely understood. Here, we explored the relationship
      between intrinsic stability of FGF proteins and their biological activity for all
      18 members of the FGF family. We report that FGF1, FGF3, FGF4, FGF6, FGF8, FGF9,
      FGF10, FGF16, FGF17, FGF18, FGF20, and FGF22 exist as unstable proteins, which
      are rapidly degraded in cell cultivation media. Biological activity of FGF1,
      FGF3, FGF4, FGF6, FGF8, FGF10, FGF16, FGF17, and FGF20 is limited by their
      instability, manifesting as failure to activate FGF receptor signal transduction
      over long periods of time, and influence specific cell behavior in vitro and in
      vivo. Stabilization via exogenous heparin binding, introduction of stabilizing
      mutations or lowering the cell cultivation temperature rescues signaling of
      unstable FGFs. Thus, the intrinsic ligand instability is an important elementary
      level of regulation in the FGF signaling system. 

PMID- 25854635
TI  - Efficacy and tolerability of levetiracetam as adjunctive therapy in Japanese
      patients with uncontrolled partial-onset seizures.
AB  - AIMS: The aim of this study was to confirm the efficacy and safety of adjunctive
      levetiracetam in adult Japanese patients with uncontrolled partial-onset
      seizures. METHODS: In a double-blind, placebo-controlled, confirmatory trial,
      eligible patients were randomized to receive levetiracetam 500, 1000, 2000, or
      3000 mg/day or placebo for 16 weeks. The primary end-point was percentage
      reduction from baseline in seizure frequency/week over a 12-week evaluation
      period. Tolerability assessments were also conducted. Findings of this and a
      previous randomized, double-blind trial were compared. RESULTS: Of 401 patients
      screened, 352 were randomized and 316 completed the study. Median percentage
      reduction in seizure frequency/week from baseline was 12.92%, 18.00%, 11.11% and
      31.67% in the levetiracetam 500, 1000, 2000 and 3000-mg groups, respectively,
      compared with 12.50% in the placebo group. Unlike the previous trial, the primary
      efficacy analysis between the levetiracetam 1000 and 3000-mg and placebo groups
      did not reach statistical significance (P = 0.067). Exploratory analyses
      demonstrated that the difference in seizure reduction versus placebo was 14.93%
      (95% confidence interval, 1.98-27.64; P = 0.025) for the levetiracetam 3000-mg
      group. All levetiracetam doses were well tolerated. The main difference between
      the two trials was a high placebo response in the present trial. CONCLUSIONS: The
      primary efficacy analysis did not reach statistical significance, a finding that
      could be attributed to an unexpectedly high placebo response. Nonetheless,
      exploratory analysis suggests that levetiracetam at 3000 mg/day may, at least
      marginally, be beneficial for patients with uncontrolled partial-onset seizures.

PMID- 25854636
TI  - Stroke prevention with rivaroxaban in higher-risk populations with atrial
      fibrillation.
AB  - BACKGROUND: Atrial fibrillation (AF), the most common cardiac arrhythmia, is a
      major risk factor for stroke. Rivaroxaban, an oral factor Xa inhibitor, is
      approved for the prevention of stroke in patients with non-valvular AF. In the
      pivotal phase III trial ROCKET AF, rivaroxaban demonstrated non-inferiority
      compared with warfarin for reducing the risk of stroke or systemic embolism (SE)
      in patients with AF (intention-to-treat analysis), without an increased risk of
      major bleeding. Superior efficacy vs. warfarin was achieved while patients were
      on study medication. Other direct oral factor Xa inhibitors have completed phase
      III clinical trials in this indication. Compared with warfarin, apixaban (in the
      ARISTOTLE trial) and edoxaban (in the ENGAGE-AF trial) were shown to be superior
      or non-inferior, respectively, for reduction in stroke or SE risk in patients
      with AF. Baseline stroke risk, as indicated by CHADS2 scores, was lower in
      patients in the ARISTOTLE and ENGAGE-AF trials than in ROCKET AF. OBJECTIVES:
      This review discusses the main findings from ROCKET AF, specifically examining
      recent subgroup analyses investigating rivaroxaban use across various patient
      types at high risk for adverse outcomes, including those with prior stroke or
      transient ischaemic attack, reduced renal function, prior myocardial infarction,
      peripheral artery disease, heart failure or patients aged >= 75 years and those
      resident in East Asia. CONCLUSIONS: These subgroup analyses demonstrate that the
      treatment effect for rivaroxaban vs. warfarin is broadly consistent across a wide
      range of patient groups, with respect to both efficacy and safety.

PMID- 25854634
TI  - Spinocerebellar ataxia type 19/22 mutations alter heterocomplex Kv4.3 channel
      function and gating in a dominant manner.
AB  - The dominantly inherited cerebellar ataxias are a heterogeneous group of
      neurodegenerative disorders caused by Purkinje cell loss in the cerebellum.
      Recently, we identified loss-of-function mutations in the KCND3 gene as the cause
      of spinocerebellar ataxia type 19/22 (SCA19/22), revealing a previously unknown
      role for the voltage-gated potassium channel, Kv4.3, in Purkinje cell survival.
      However, how mutant Kv4.3 affects wild-type Kv4.3 channel functioning remains
      unknown. We provide evidence that SCA19/22-mutant Kv4.3 exerts a dominant
      negative effect on the trafficking and surface expression of wild-type Kv4.3 in
      the absence of its regulatory subunit, KChIP2. Notably, this dominant negative
      effect can be rescued by the presence of KChIP2. We also found that all SCA19/22
      mutant subunits either suppress wild-type Kv4.3 current amplitude or alter
      channel gating in a dominant manner. Our findings suggest that altered Kv4.3
      channel localization and/or functioning resulting from SCA19/22 mutations may
      lead to Purkinje cell loss, neurodegeneration and ataxia. 

PMID- 25854633
TI  - Fat deposition and accumulation in the damaged and inflamed skeletal muscle:
      cellular and molecular players.
AB  - The skeletal muscle has the capacity to repair damage by the activation and
      differentiation of fiber sub-laminar satellite cells. Regeneration impairment due
      to reduced satellite cells number and/or functional capacity leads to fiber
      substitution with ectopic tissues including fat and fibrous tissue and to the
      loss of muscle functions. Muscle mesenchymal cells that in physiological
      conditions sustain or directly contribute to regeneration differentiate in
      adipocytes in patients with persistent damage and inflammation of the skeletal
      muscle. These cells comprise the fibro-adipogenic precursors, the PW1-expressing
      cells and some interstitial cells associated with vessels (pericytes,
      mesoangioblasts and myoendothelial cells). Resident fibroblasts that are
      responsible for collagen deposition and extracellular matrix remodeling during
      regeneration yield fibrotic tissue and can differentiate into adipose cells. Some
      authors have also proposed that satellite cells themselves could
      transdifferentiate into adipocytes, although recent results by lineage tracing
      techniques seem to put this theory to discussion. This review summarizes findings
      about muscle resident mesenchymal cell differentiation in adipocytes and
      recapitulates the molecular mediators involved in intramuscular adipose tissue
      deposition. 

PMID- 25854638
TI  - Physiological load associated with a Zumba((r)) fitness workout: a comparison
      pilot study between classes and a DVD.
AB  - The objectives were to compare the metabolic load elicited by Zumba((r)) classes
      and DVD workouts and link the physiological responses to participants'
      psychological characteristics. Fifteen women (25.4 +/- 4.3 years old; 164.9 +/-
      5.1 cm; 56.9 +/- 5.8 kg; 23.9 +/- 4.9% body fat) performed three Zumba((r))
      classes and three Zumba((r)) DVD workouts using a repeated measure design. Energy
      expenditure was assessed by extrapolating oxygen cost from heart rate (HR) using
      regressions from a preliminary incremental running test. Differences between
      Zumba((r)) classes and Zumba((r)) DVD workouts were assessed by Student's T tests
      and repeated measures analysis of variance and correlations between physiological
      and psychological variables by the Pearson's coefficient. Results showed that
      Zumba((r)) classes allowed greater energy expenditure compared to Zumba((r)) DVD
      workouts (6.8 +/- 0.9 vs 5.6 +/- 0.9 kcal . min(-1), 95% confidence interval (CI)
      limits: 0.3-2.1, P = 0.016), with significant differences in the time spent with
      a HR above 85% of HR reserve (14.7 vs 1.7%, 95% CI: 5.6-20.4, P = 0.021).
      Furthermore, women with a greater autonomy score showed a smaller difference
      between DVD and class (r = 0.511, P = 0.048), while greater differences were
      shown in women with greater interpersonal skills (r = -0.563, P = 0.028). The
      results suggest that while both types of workouts are suitable to maintain
      fitness Zumba((r)) classes allow greater energy expenditure.

PMID- 25854637
TI  - A pathological perspective on the natural history of cerebral atherosclerosis.
AB  - BACKGROUND: The natural history of intracranial large artery atherosclerosis has
      been mainly described from lumen-based imaging studies, and much of what is
      reported to be known about atherosclerosis is derived from non-cerebral arteries.
      AIMS: To test the hypothesis that atherosclerosis is only partially represented
      by stenosis and that advanced atherosclerosis is more common that severe stenosis
      in noncardioembolic infarcts. METHODS: Cerebral large arteries from 196 autopsy
      cases were studied. The revised American Heart Association classification for
      atherosclerosis was used to determine the phenotype in each available artery.
      Cross-sectional lumen stenosis was obtained as defined by the Glagov's method.
      RESULTS: As age of cases increased, there was a progressive increment in the
      frequency of atherosclerotic lesions, rising from 5% of all arteries at age 20
      40, to more than 40% at age 60 or older. Stenosis also increased with age: less
      than 3% of the arteries in those <=50 years had >40% stenosis, while one out of
      five arteries in those >80 years had >40% stenosis. In most cases (80%),
      atherosclerosis and stenosis were directly related. However, one out of five
      cases with advanced atherosclerosis had <30% stenosis. In arteries supplying
      brain areas with noncardioembolic infarcts, the majority of segments exhibiting
      advanced atherosclerosis had lumen stenosis of <40%. CONCLUSION: Although
      intracranial atherosclerosis is typically associated with stenosis, a substantial
      minority of cases shows advanced atherosclerosis in the absence of stenosis >40%.
      Definitions based solely on stenosis may underestimate the extent and role of
      intracranial large artery atherosclerosis.

PMID- 25854639
TI  - Identifying the immunomodulatory components of helminths.
AB  - Immunomodulatory components of helminths offer great promise as an entirely new
      class of biologics for the treatment of inflammatory diseases. Here, we discuss
      the emerging themes in helminth-driven immunomodulation in the context of
      therapeutic drug discovery. We broadly define the approaches that are currently
      applied by researchers to identify these helminth molecules, highlighting key
      areas of potential exploitation that have been mostly neglected thus far, notably
      small molecules. Finally, we propose that the investigation of immunomodulatory
      compounds will enable the translation of current and future research efforts into
      potential treatments for autoimmune and allergic diseases, while at the same time
      yielding new insights into the molecular interface of host-parasite biology. 

PMID- 25854640
TI  - Single CuO nanowires decorated with size-selected Pd nanoparticles for CO sensing
      in humid atmosphere.
AB  - We report on conductometric gas sensors based on single CuO nanowires and compare
      the carbon monoxide (CO) sensing properties of pristine as well as Pd
      nanoparticle decorated devices in humid atmosphere. Magnetron sputter inert gas
      aggregation combined with a quadrupole mass filter for cluster size selection was
      used for single-step Pd nanoparticle deposition in the soft landing regime.
      Uniformly dispersed, crystalline Pd nanoparticles with size-selected diameters
      around 5 nm were deposited on single CuO nanowire devices in a four point
      configuration. During gas sensing experiments in humid synthetic air,
      significantly enhanced CO response for CuO nanowires decorated with Pd
      nanoparticles was observed, which validates that magnetron sputter gas
      aggregation is very well suited for the realization of nanoparticle
      functionalized sensors with improved performance. 

PMID- 25854641
TI  - Prophylactic administration of fucoidan represses cancer metastasis by inhibiting
      vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) in
      Lewis tumor-bearing mice.
AB  - Fucoidan, a heparin-like sulfated polysaccharide, is rich in brown algae. It has
      a wide assortment of protective activities against cancer, for example, induction
      of hepatocellular carcinoma senescence, induction of human breast and colon
      carcinoma apoptosis, and impediment of lung cancer cells migration and invasion.
      However, the anti-metastatic mechanism that fucoidan exploits remains elusive. In
      this report, we explored the effects of fucoidan on cachectic symptoms, tumor
      development, lung carcinoma cell spreading and proliferation, as well as
      expression of metastasis-associated proteins in the Lewis lung carcinoma (LLC)
      cells-inoculated mice model. We discovered that administration of fucoidan has
      prophylactic effects on mitigation of cachectic body weight loss and improvement
      of lung masses in tumor-inoculated mice. These desired effects are attributed to
      inhibition of LLC spreading and proliferation in lung tissues. Fucoidan also down
      regulates expression of matrix metalloproteinases (MMPs), nuclear factor kappa
      light-chain-enhancer of activated B cells (NF-kappaB) and vascular endothelial
      growth factor (VEGF). Moreover, the tumor-bearing mice supplemented with fucoidan
      indeed benefit from an ensemble of the chemo-phylacticity. The fact is that
      fucoidan significantly decreases viability, migration, invasion, and MMPs
      activities of LLC cells. In summary, fucoidan is suitable to act as a chemo
      preventative agent for minimizing cachectic symptoms as well as inhibiting lung
      carcinoma metastasis through down-regulating metastatic factors VEGF and MMPs. 

PMID- 25854642
TI  - 3-[4-(1H-indol-3-yl)-1,3-thiazol-2-yl]-1H-pyrrolo[2,3-b]pyridines, nortopsentin
      analogues with antiproliferative activity.
AB  - A new series of nortopsentin analogues, in which the imidazole ring of the
      natural product was replaced by thiazole and the indole unit bound to position 2
      of the thiazole ring was substituted by a 7-azaindole moiety, was efficiently
      synthesized. Two of the new nortopsentin analogues showed good antiproliferative
      effect against the totality of the NCI full panel of human tumor cell lines (~60)
      having GI50 values ranging from low micromolar to nanomolar level. The mechanism
      of the antiproliferative effect of these derivatives, investigated on human
      hepatoma HepG2 cells, was pro-apoptotic, being associated with externalization of
      plasma membrane phosphatidylserine and mitochondrial dysfunction. Moreover, the
      compounds induced a concentration-dependent accumulation of cells in the
      subG0/G1phase, while confined viable cells in G2/M phase. 

PMID- 25854644
TI  - Bioactive terpenes from marine-derived fungi.
AB  - Marine-derived fungi continue to be a prolific source of secondary metabolites
      showing diverse bioactivities. Terpenoids from marine-derived fungi exhibit wide
      structural diversity including numerous compounds with pronounced biological
      activities. In this review, we survey the last five years' reports on terpenoidal
      metabolites from marine-derived fungi with particular attention on those showing
      marked biological activities. 

PMID- 25854645
TI  - Two novel antioxidant nonapeptides from protein hydrolysate of skate (Raja
      porosa) muscle.
AB  - In the current study, the preparation conditions of neutrase hydrolysate (SMH)
      from skate (Raja porosa) muscle protein were optimized using orthogonal L9(3)4
      tests, and R values indicated that pH was the most important factor affecting HO.
      scavenging activity of SMH. Under the optimum conditions of pH 7.0, enzymolysis
      temperature 60  degrees C, enzyme/substrate ratio (E/S) 2%, and enzymolysis time
      5 h, EC50 of SMH on HO. was 2.14 +/- 0.17 mg/mL. Using ultrafiltration, gel
      filtration chromatography, and RP-HPLC, two novel antioxidant nonapeptides (SP-A
      and SP-B) were isolated from SMH and their amino acid sequences were found to be
      APPTAYAQS (SP-A) and NWDMEKIWD (SP-B) with calculated molecular masses of 904.98
      Da and 1236.38 Da, respectively. Both showed strong antioxidant activities. SP-A
      and SP-B exhibited good scavenging activities on HO. (EC50 0.390 and 0.176
      mg/mL), DPPH. (EC50 0.614 and 0.289 mg/mL), and O2-. (EC50 0.215 and 0.132 mg/mL)
      in a dose-dependent manner. SP-B was also effective against lipid peroxidation in
      the model system. The aromatic (2Trp), acidic (2Asp and Glu), and basic (Lys)
      amino acid residues within the sequences of SP-B might account for its pronounced
      antioxidant activity. The results of this study suggested that protein
      hydrolysate and peptides from skate muscle might be effective as food additives
      for retarding lipid peroxidation occurring in foodstuffs. 

PMID- 25854643
TI  - Marine extremophiles: a source of hydrolases for biotechnological applications.
AB  - The marine environment covers almost three quarters of the planet and is where
      evolution took its first steps. Extremophile microorganisms are found in several
      extreme marine environments, such as hydrothermal vents, hot springs, salty lakes
      and deep-sea floors. The ability of these microorganisms to support extremes of
      temperature, salinity and pressure demonstrates their great potential for
      biotechnological processes. Hydrolases including amylases, cellulases, peptidases
      and lipases from hyperthermophiles, psychrophiles, halophiles and piezophiles
      have been investigated for these reasons. Extremozymes are adapted to work in
      harsh physical-chemical conditions and their use in various industrial
      applications such as the biofuel, pharmaceutical, fine chemicals and food
      industries has increased. The understanding of the specific factors that confer
      the ability to withstand extreme habitats on such enzymes has become a priority
      for their biotechnological use. The most studied marine extremophiles are
      prokaryotes and in this review, we present the most studied archaea and bacteria
      extremophiles and their hydrolases, and discuss their use for industrial
      applications. 

PMID- 25854647
TI  - Can oral vitamin D prevent the cardiovascular diseases among migrants in
      Australia? Provider perspective using Markov modelling.
AB  - The study was designed to model the effectiveness and cost effectiveness of oral
      Vitamin D supplementation as a primary prevention strategy for cardiovascular
      disease among a migrant population in Australia. It was carried out in the
      Community Health Service, Kensington, Melbourne. Best-case scenario analysis
      using a Markov model was employed to look at the health care providers'
      perspective. Adult migrants who were vitamin D deficient and free from
      cardiovascular disease visiting the medical centre at least once during the
      period from 1 January 2010 to 31 December 2012 were included in the study. The
      blood pressure-lowering effect of vitamin D was taken from a published meta
      analysis and applied in the Framingham 10 year cardiovascular risk algorithm
      (with and without oral vitamin D supplements) to generate the probabilities of
      cardiovascular events. A Markov decision model was used to estimate the provider
      costs associated with the events and treatments. Uncertainties were derived by
      Monte Carlo simulation. Vitamin D oral supplementation (1000 IU/day) for 10 years
      could potentially prevent 31 (interquartile range (IQR) 26 to 37) non-fatal and
      11 (IQR 10 to 15) fatal cardiovascular events in a migrant population of 10,000
      assuming 100% compliance. The provider perspective incremental cost effectiveness
      per year of life saved was AU$3,992 (IQR 583 to 8558). This study suggests
      subsidised supplementation of oral vitamin D may be a cost effective intervention
      to reduce non-fatal and fatal cardiovascular outcomes in high-risk migrant
      populations.

PMID- 25854646
TI  - Marine natural products as breast cancer resistance protein inhibitors.
AB  - Breast cancer resistance protein (BCRP) is a protein belonging to the ATP-binding
      cassette (ABC) transporter superfamily that has clinical relevance due to its
      multi-drug resistance properties in cancer. BCRP can be associated with clinical
      cancer drug resistance, in particular acute myelogenous or acute lymphocytic
      leukemias. The overexpression of BCRP contributes to the resistance of several
      chemotherapeutic drugs, such as topotecan, methotrexate, mitoxantrone,
      doxorubicin and daunorubicin. The Food and Drugs Administration has already
      recognized that BCRP is clinically one of the most important drug transporters,
      mainly because it leads to a reduction of clinical efficacy of various anticancer
      drugs through its ATP-dependent drug efflux pump function as well as its apparent
      participation in drug resistance. This review article aims to summarize the
      different research findings on marine natural products with BCRP inhibiting
      activity. In this sense, the potential modulation of physiological targets of
      BCRP by natural or synthetic compounds offers a great possibility for the
      discovery of new drugs and valuable research tools to recognize the function of
      the complex ABC-transporters. 

PMID- 25854648
TI  - Using cumulative sums of martingale residuals for model checking in nested case
      control studies.
AB  - Standard use of Cox regression requires collection of covariate information for
      all individuals in a cohort even when only a small fraction of them experiences
      the event of interest (fail). This may be very expensive for large cohorts.
      Further in biomarker studies, it will imply a waste of valuable biological
      material that one may want to save for future studies. A nested case-control
      study offers a useful alternative. For this design, covariate information is only
      needed for the failing individuals (cases) and a sample of controls selected from
      the cases' at-risk sets. Methods based on martingale residuals are useful for
      checking the fit of Cox's regression model for cohort data. But similar methods
      have so far not been developed for nested case-control data. In this article, it
      is described how one may define martingale residuals for nested case-control
      data, and it is shown how plots and tests based on cumulative sums of martingale
      residuals may be used to check model fit. The plots and tests may be obtained
      using available software. 

PMID- 25854649
TI  - Acute management of brain arteriovenous malformations.
AB  - OPINION STATEMENT: Major reasons to treat brain arteriovenous malformations
      (AVMs) are to reduce the risk of brain hemorrhage, control intractable seizure,
      and in some cases alleviate neurologic deficits. Once an AVM has hemorrhaged, the
      risk of further hemorrhage is increased and it should be treated. The treatment
      plan ideally is based on interdisciplinary discussion between neurosurgery,
      endovascular neuroradiology, and radiotherapy, moderated by neurology in an
      experienced center. Complete removal or obliteration of the malformation should
      be the goal, as partial treatment only exposes the patient to treatment risks
      with a residual hemorrhage risk. If an AVM is surgically accessible with
      acceptable treatment risk, neurosurgical removal leads to the fastest and most
      complete reduction of hemorrhage risk. Radiotherapy is best used in small AVMs
      with contraindications to surgery. Endovascular embolization can be used as an
      adjunct for both to facilitate removal or obliteration or to reduce risks from
      associated aneurysms or high-flow fistulae, and may in some cases lead to
      complete occlusion. Unbled AVMs require a thorough assessment of projected
      hemorrhage risk versus treatment risks, as the natural course is influenced by
      clinical and morphological factors. Given recent scientific evidence, those with
      low projected hemorrhage risks should be managed conservatively, receiving the
      best medical treatment of accompanying symptoms, and careful clinical and follow
      up imaging monitoring. Thorough and objective counselling of the patients about
      pros and contras of therapy, detailed explanation of recommendations, and
      possible reevaluation of treatment decisions at later timepoints are recommended.

PMID- 25854650
TI  - Update on therapy for narcolepsy.
AB  - OPINION STATEMENT: Narcolepsy is a severe, incurable, neurological disorder that
      is treated by pharmacological management of its symptoms. The main symptoms are
      excessive daytime sleepiness (EDS) and cataplexy, although addition symptoms that
      may require treatment include sleep paralysis, hypnagogic hallucinations, and
      disturbed nocturnal sleep. Sodium oxybate and modafinil/armodafinil are the first
      line treatments for EDS, and sodium oxybate for cataplexy. Sodium oxybate treats
      all the symptoms of narcolepsy, whereas modafinil is effective for EDS only.
      Alternative medications for EDS include methylphenidate or amphetamines such as
      dextroamphetamine, lisdexamfetamine, methamphetamine, or combination amphetamine
      salts. Non-FDA approved medications for cataplexy include norepinephrine reuptake
      inhibitors such as venlafaxine or atomoxetine. Combination therapy can be more
      effective for sleepiness such as sodium oxybate and modafinil/armodafinil.
      Medication for narcolepsy is generally well tolerated and usually required life
      long although does not eliminate all symptoms of narcolepsy.

PMID- 25854651
TI  - Management of pediatric traumatic brain injury.
AB  - OPINION STATEMENT: Pediatric severe traumatic brain injury continues to be a
      major cause of disability and death. Rapid initial airway and hemodynamic
      stabilization is critical, followed by the need for immediate recognition of
      intracranial pathology that requires neurosurgical intervention. Intracranial
      hypertension and cerebral hypoperfusion have been recognized as major insults
      after trauma and management should be directed at preventing both. Sedation with
      opioids, moderate hyperventilation to arterial carbon dioxide level of 35-40
      mmHg, hyperosmolar therapy with 3 % saline or mannitol, normothermia, and
      cerebrospinal fluid drainage continue to be the cornerstones of initial
      management of intracranial hypertension (intracranial pressure >20 mmHg).
      Refractory intracranial hypertension is treated with high-dose barbiturate
      therapy to achieve medical burst suppression on electroencephalography and
      decompressive craniectomy. In addition, those children require antiepileptic
      medications for seizure prophylaxis, adequate nutritional management, and early
      physical therapy and rehabilitation referrals. Most of the evidence for care of
      children with brain injury comes from center-specific practice and experience
      rather than objective data. This lack of evidence provides the ground for ongoing
      research; nevertheless, outcomes after traumatic brain injury continue to show
      improvement.

PMID- 25854652
TI  - Emergency management of ischemic stroke in children.
AB  - OPINION STATEMENT: Children who present with acute neurological symptoms
      suggestive of a stroke need immediate clinical assessment and urgent neuroimaging
      to confirm diagnosis. Magnetic resonance imaging (MRI) is the investigation of
      first choice due to limited sensitivity of computed tomography (CT) for detection
      of ischaemia. Acute monitoring should include monitoring of blood pressure and
      body temperature, and neurological observations. Surveillance in a paediatric
      high dependency or intensive care unit and neurosurgical consultation are
      mandatory in children with large infarcts at risk of developing malignant oedema
      or haemorrhagic transformation. Thrombolysis and/or endovascular treatment,
      whilst not currently approved for use in children, may be considered when stroke
      diagnosis is confirmed within 4.5 to 6 h, provided there are no contraindications
      on standard adult criteria. Standard treatment consists of aspirin, but
      anticoagulation therapy is frequently prescribed in stroke due to cardiac disease
      and extracranial dissection. Steroids and immunosuppression have a definite place
      in children with proven vasculitis, but their role in focal arteriopathies is
      less clear. Decompressive craniotomy should be considered in children with
      deteriorating consciousness or signs of raised intracranial pressure.

PMID- 25854654
TI  - Risk factors for venous thromboembolism after total hip and total knee
      arthroplasty: a meta-analysis.
AB  - INTRODUCTION: Venous thromboembolism (VTE) is a common complication after total
      hip arthroplasty (THA) or total knee arthroplasty (TKA) and may be the cause for
      a secondary PE and associated morbidity/mortality. We performed a systematic
      literature review of risk factors and risk reduction of VTE after THA or TKA.
      MATERIALS AND METHODS: A systematic search of PubMed database, the Cochrane
      Library, OVID MEDLINE and American Academy of Orthopaedic Surgeons (AAOS),
      without restriction of publication data and language, was conducted. We performed
      a meta-analysis of ten factors for VTE after THA or TKA. Four authors
      independently assessed data extraction and quality of the studies using the
      Newcastle-Ottawa Scale (NOS) as quality assessment tool. Assessment of
      heterogeneity and analysis of data were operated by Review Manager 5.2.9.
      RESULTS: Fourteen retrospective case-control or prospective cohort studies, which
      included 18,075 patients who developed VTE after THA or TKA of a total of
      1,723,350 cases, were selected. Our results demonstrated that, among all ten
      factors investigated, 3 main risk factors were significantly associated with VTE
      after THA or TKA: history of VTE (RR > 10.6), varicose vein (RR > 2.7) and
      congestive cardiac failure (RR 2). There was also an increase of VTE risk ranging
      from 8 to 30 % for female gender < age (>=80) < hypertension < (active) cancer <
      obesity (BMI >= 30) < (black) race. Data analysis revealed that diabetes mellitus
      had no significant relationship with VTE after THA or TKA. CONCLUSIONS: This
      study highlighted the role of nine significant risk factors in the development of
      VTE after THA or TKA. Among all risk factors, history of VTE seems the one main
      indication for more potent anticoagulation. All other risk factors need to be
      considered and discussed with patients individually and balanced against the risk
      of bleeding and infection. Individual patient risk assessment, rather than a
      "blanket policy", is considered the best management strategy before deciding on
      the type of chemical prophylaxis.

PMID- 25854653
TI  - A versatile nano display platform from bacterial spore coat proteins.
AB  - Dormant bacterial spores are encased in a thick protein shell, the 'coat', which
      contains ~70 different proteins. The coat protects the spore from environmental
      insults, and is among the most durable static structures in biology. Owing to
      extensive cross-linking among coat proteins, this structure has been recalcitrant
      to detailed biochemical analysis, so molecular details of how it assembles are
      largely unknown. Here, we reconstitute the basement layer of the coat atop
      spherical membranes supported by silica beads to create artificial spore-like
      particles. We report that these synthetic spore husk-encased lipid bilayers
      (SSHELs) assemble and polymerize into a static structure, mimicking in vivo
      basement layer assembly during sporulation in Bacillus subtilis. In addition, we
      demonstrate that SSHELs may be easily covalently modified with small molecules
      and proteins. We propose that SSHELs may be versatile display platforms for drugs
      and vaccines in clinical settings, or for enzymes that neutralize pollutants for
      environmental remediation. 

PMID- 25854655
TI  - What is the fate of clubfoot patients treated by posteromedial release?
AB  - INTRODUCTION: Management and long-term results of operatively treated clubfoot
      deformity still remains controversial. The aim of this study was to evaluate the
      radiological and clinical results of adult clubfoot patients treated with
      posteromedial release. MATERIALS AND METHODS: Between 2005 and 2012, we evaluated
      patients with congenital foot deformities regarding clubfoot who were operatively
      treated with complete posteromedial release. Out of 320 patients evaluated, 29
      patients (40 feet) were included the study. We also included foot radiographies
      of 40 healthy adults. Talocalcaneal angle on the dorsoplantar projection (TC-DP)
      and lateral projection (TC-L) and talus-first metatarsal angle on the
      dorsoplantar projection (TFM-DP) were measured for both clubfeet and control
      groups. Laaveg-Ponseti functional rating system was used for clinical evaluation
      and measurement of lower leg circumference was used for detection of atrophy.
      RESULTS: The average age was 21.5 years (range 19-34). The mean TC-DP angle was
      16.97 in the clubfeet group and 21.03 in the control group. The mean TC-L angle
      was 23.34 in the clubfeet group and 33.98 in the control group. The mean TFM-DP
      angle was 9.02 in the clubfeet group and 7.9 in control group. There were
      statistically significant difference between clubfoot and control groups
      regarding the TC-DP angle and the TC-L angle. The average Laaveg-Ponseti score
      was 74 points (range 42-96). While no significant correlations could be detected
      between the TC-DP angle, the TC-L angle, the TFM-DP angle and the functional
      score, a significant correlation was detected between circumferential measurement
      of lower leg and functional score (p = 0.04). CONCLUSION: Functional outcome may
      be affected by lower leg muscular atrophy instead of foot alignment disturbance.
      Lastly we believe that results for treatment of clubfoot-a three-dimensional
      deformity-need to be evaluated with three-dimensional imaging techniques.

PMID- 25854656
TI  - A quantitative approach to blastocyst quality evaluation: morphometric analysis
      and related IVF outcomes.
AB  - PURPOSE: To quantify blastocyst morphologic parameters with a feasible and
      standardized tool, investigating their predictive value on implantation outcome.
      METHOD: The study retrospectively analyzes 124 blastocysts from 75 patients.
      Quantitative measurements of blastocyst expansion, inner cell mass and
      trophoectoderm were taken using digital image analysis software. RESULT(S):
      Blastocysts areas were found to be ranging from 11626.2 up to 35076.4 MUm(2). The
      area of an early blastocyst is A <= 18500 MUm(2) with a mean diameter d = 140 +/-
      9 MUm, and the area of an expanded blastocyst is A >= 24000 with d = 190 +/- 9
      MUm. While blastocyst mean area was not related to implantation rate, more
      expanded blastocysts displayed a significantly higher implantation rate.
      Trophoectoderm cell number is a predictor of positive outcome: since a higher of
      cells (25.6 +/- 11.3 vs 16.3 +/- 12.8) 'forming a tightly knit epithelium is
      prognostic of implantation potential. Conversely, inner cell mass size is
      significantly related to implantation only in expanded blastocysts (3122.7 +/-
      739.0 vs. 2978.1 +/- 366.0 MUm(2)). CONCLUSION(S): Evaluation of blastocyst
      morphology with a digital image system could be a valuable tool to standardize
      blastocyst grading based on quantitative parameters. Therefore, digital analysis
      may be helpful in identifying the best blastocyst to transfer.

PMID- 25854658
TI  - Nursing, nurses, and ethics.

PMID- 25854657
TI  - Female offspring sired by diet induced obese male mice display impaired
      blastocyst development with molecular alterations to their ovaries, oocytes and
      cumulus cells.
AB  - PURPOSE: To investigate the impacts that a paternal high fat diet (HFD) has on
      embryology, ovarian/cumulus cell gene expression and COC metabolism from female
      offspring, using a mouse model. METHODS: Founder male mice were either fed a
      control diet (CD) or a HFD for 12 weeks. The HFD induced obesity but not
      diabetes, and founder males were then mated to normal weight CD fed female mice.
      Female offspring were maintained on a CD, super-ovulated, mated and the resultant
      zygotes were cultured to the blastocyst stage for embryo morphology, blastocyst
      cell number and apoptosis assessment. Ovaries and cumulus cells from offspring
      were collected for gene expression analysis of selected genes that maintain
      chromatin remodeling and endoplasmic reticulum (ER), metabolic and inflammatory
      homeostasis. Cumulus/oocyte complexes were also investigated for glucose uptake
      and lipid accumulation. RESULTS: Female offspring sired by obese fathers produced
      embryos with delayed development and impaired quality, displayed increases in
      ovarian expression of Glut1, Glut3 and Glut4, and an increase in cumulus cell
      expression of Glut4. Interestingly their COCs did take up more glucose, but did
      accumulate more lipid. CONCLUSIONS: A paternal HFD is associated with
      subfertility in female offspring despite the offspring being fed a CD and this
      subfertility is concomitant with ovarian/cumulus cell molecular alterations and
      increased lipid accumulation.

PMID- 25854659
TI  - Diagnosis, prevention and treatment of accidental and perioperative hypothermia.
AB  - Accidental hypothermia and its variant, perioperative hypothermia, is a rather
      common clinical phenomenon in patients. This is surprising because the negative
      effects on clinical outcomes are well described and effective patient-warming
      devices are available today. The aim of this paper is to describe the physiologic
      background of accidental and perioperative hypothermia, the clinical relevance
      and existing prophylaxis and treatment options. Patient warming techniques will
      be discussed in detail. Remaining technical and clinical challenges and the need
      for further research will be addressed. We will present existing guidelines and
      standards and analyse the impact of accidental and perioperative hypothermia on
      cost effectiveness. 

PMID- 25854660
TI  - Development of a computer-based automated pure tone hearing screening device: a
      preliminary clinical trial.
AB  - Hearing screening is important for the early detection of hearing loss. The
      requirements of specialized equipment, skilled personnel, and quiet environments
      for valid screening results limit its application in schools and health clinics.
      This study aimed to develop an automated hearing screening kit (auto-kit) with
      the capability of realtime noise level monitoring to ensure that the screening is
      performed in an environment that conforms to the standard. The auto-kit consists
      of a laptop, a 24-bit resolution sound card, headphones, a microphone, and a
      graphical user interface, which is calibrated according to the American National
      Standards Institute S3.6-2004 standard. The auto-kit can present four test tones
      (500, 1000, 2000, and 4000 Hz) at 25 or 40 dB HL screening cut-off level. The
      clinical results at 40 dB HL screening cut-off level showed that the auto-kit has
      a sensitivity of 92.5% and a specificity of 75.0%. Because the 500 Hz test tone
      is not included in the standard hearing screening procedure, it can be excluded
      from the auto-kit test procedure. The exclusion of 500 Hz test tone improved the
      specificity of the auto-kit from 75.0% to 92.3%, which suggests that the auto-kit
      could be a valid hearing screening device. In conclusion, the auto-kit may be a
      valuable hearing screening tool, especially in countries where resources are
      limited. 

PMID- 25854661
TI  - Control of a HexaPOD treatment couch for robot-assisted radiotherapy.
AB  - Moving tumors, for example in the vicinity of the lungs, pose a challenging
      problem in radiotherapy, as healthy tissue should not be irradiated. Apart from
      gating approaches, one standard method is to irradiate the complete volume within
      which a tumor moves plus a safety margin containing a considerable volume of
      healthy tissue. This work deals with a system for tumor motion compensation using
      the HexaPOD(r) robotic treatment couch (Medical Intelligence GmbH, Schwabmunchen,
      Germany). The HexaPOD, carrying the patient during treatment, is instructed to
      perform translational movements such that the tumor motion, from the beams-eye
      view of the linear accelerator, is eliminated. The dynamics of the HexaPOD are
      characterized by time delays, saturations, and other non-linearities that make
      the design of control a challenging task. The focus of this work lies on two
      control methods for the HexaPOD that can be used for reference tracking. The
      first method uses a model predictive controller based on a model gained through
      system identification methods, and the second method uses a position control
      scheme useful for reference tracking. We compared the tracking performance of
      both methods in various experiments with real hardware using ideal reference
      trajectories, prerecorded patient trajectories, and human volunteers whose
      breathing motion was compensated by the system. 

PMID- 25854662
TI  - Mechanical testing of an absorbable hybrid fusion cage for the cervical spine.
AB  - Conventional fusion devices ("cages") are often used to join two vertebrae of the
      human spine and generally remain in the body for a lifetime and can theoretically
      lead to any complications. Therefore, an absorbable hybrid fusion cage consisting
      of a magnesium skeleton infiltrated with an absorbable polymer [poly-epsilon
      caprolactone (PCL)] has been developed. The primary objective of the cage is to
      ensure an adequate stiffness of the disc space directly after the operation and
      to encourage the ingrowth of the new bone tissue to secure long life stability.
      Once a sufficiently rigid bone connection is formed, the implant should be
      absorbed. The purpose of this first study on the new absorbable fusion cage was
      to investigate the mechanical properties in vitro. Tensile tests were performed
      with tensile specimens type 1BA according to DIN EN ISO 527 made of PCL foamed
      using controlled expansion of saturated polymers (CESP). Furthermore, cyclic
      compression tests and compression tests with steady movement were performed with
      different designs of the new cage. Compression tests were also performed with
      vertebral endplates of ovine cadaveric spines. Foaming of PCL resulted in a
      modulus of elasticity of 135 MPa, which is approximately one third of unfoamed
      PCL. The results indicate that the initial compression strength of the implants
      should be adequate for the implantation in the cervical spine. 

PMID- 25854663
TI  - Determination of the frictional coefficient of the implant-antler interface:
      experimental approach.
AB  - The similar bone structure of reindeer antler to human bone permits studying the
      osseointegration of dental implants in the jawbone. As the friction is one of the
      major factors that have a significant influence on the initial stability of
      immediately loaded dental implants, it is essential to define the frictional
      coefficient of the implant-antler interface. In this study, the kinetic
      frictional forces at the implant-antler interface were measured experimentally
      using an optomechanical setup and a stepping motor controller under different
      axial loads and sliding velocities. The corresponding mean values of the static
      and kinetic frictional coefficients were within the range of 0.5-0.7 and 0.3-0.5,
      respectively. An increase in the frictional forces with increasing applied axial
      loads was registered. The measurements showed an evidence of a decrease in the
      magnitude of the frictional coefficient with increasing sliding velocity. The
      results of this study provide a considerable assessment to clarify the suitable
      frictional coefficient to be used in the finite element contact analysis of
      antler specimens. 

PMID- 25854664
TI  - Section plane selection influences the results of histomorphometric studies: the
      example of dental implants.
AB  - OBJECTIVES: This study was designed to determine and statistically analyze bone
      to-implant contact (BIC) values for human specimens segmented in at least two
      different locations. MATERIALS AND METHODS: Samples of human bone with fractured
      osseointegrated implants were obtained from six patients. Sections were prepared,
      dehydrated, and resin infiltrated. Undecalcified bone sections were produced
      using the thin-section technique according to Donath, ultimately obtaining a
      section thickness of approximately 20 MUm. Fifteen specimens were available for
      histomorphometry. The bone sections were digitized and analyzed. The bone-to
      metal contact (BMC) parameter was determined histomorphometrically. The BMC was
      returned in terms of the visibly bone-covered implant surfaces as a percentage of
      the total implant surface shown. RESULTS: The values obtained for the six
      implants were arranged as six maximum-distance pairs and tested for significance
      using the t-test for dependent samples. The mean difference in BIC was 11.69+/
      9.79%. The two-sided test showed a significant difference (p=0.033). CONCLUSION:
      The accidental or deliberate choice of section plane for a bone-implant block has
      an influence on the BIC value. To make BIC values more comparable, a
      standardization of section planes is desirable.

PMID- 25854665
TI  - Determination of fetal heart rate from abdominal signals: evaluation of beat-to
      beat accuracy in relation to the direct fetal electrocardiogram.
AB  - The main aim of our work was to assess the reliability of indirect abdominal
      electrocardiography as an alternative to the commonly used Doppler ultrasound
      monitoring technique. As a reference method, we used direct fetal
      electrocardiography. Direct and abdominal signals were acquired simultaneously,
      using dedicated instrumentation. The developed method of maternal signal
      suppression as well as fetal QRS complexes detection was presented. Recordings
      were collected during established labors, each consisted of four signals from the
      maternal abdomen and the reference signal acquired directly from the fetal head.
      After assessing the performance of the QRS detector, the accuracy of fetal heart
      rate measurement was evaluated. Additionally, to reduce the influence of
      inaccurately detected R-waves, some validation rules were proposed. The obtained
      results revealed that the indirect method is able to provide an accuracy
      sufficient for a reliable assessment of fetal heart rate variability. However,
      the method is very sensitive to recording conditions, influencing the quality of
      signals. Our investigations confirmed that abdominal electrocardiography, even in
      its current stage of development, offers an accuracy equal to or higher than an
      ultrasound method, at the same time providing some additional features. 

PMID- 25854666
TI  - Feature selection using binary particle swarm optimization and support vector
      machines for medical diagnosis.
AB  - In this article, we propose a feature selection strategy using a binary particle
      swarm optimization algorithm for the diagnosis of different medical diseases. The
      support vector machines were used for the fitness function of the binary particle
      swarm optimization. We evaluated our proposed method on four databases from the
      machine learning repository, including the single proton emission computed
      tomography heart database, the Wisconsin breast cancer data set, the Pima Indians
      diabetes database, and the Dermatology data set. The results indicate that, with
      selected less number of features, we obtained a higher accuracy in diagnosing
      heart, cancer, diabetes, and erythematosquamous diseases. The results were
      compared with the traditional feature selection methods, namely, the F-score and
      the information gain, and a superior accuracy was obtained with our method.
      Compared to the genetic algorithm for feature selection, the results of the
      proposed method show a higher accuracy in all of the data, except in one. In
      addition, in comparison with other methods that used the same data, our approach
      has a higher performance using less number of features. 

PMID- 25854667
TI  - Interoperability optimization in healthcare collaboration networks.
AB  - Interoperability is one of the most challenging concerns that face healthcare
      information system (HIS) actors. Interoperability implementation in this context
      may be a data exchange interfacing, a service oriented interaction or even a
      composition of new composite healthcare processes. In fact, optimizing efforts of
      interoperability achievement is a key requirement to effectively setup, develop
      and evolve intra- and interorganizational collaboration. To ensure
      interoperability project effectiveness, this paper proposes a modeling
      representation of health processes interoperability evolution. Interoperability
      degrees of involved automated processes are assessed using a ratio metric, taking
      into account all significant aspects, such as potentiality, compatibility and
      operational performance. Then, a particle swarm optimization algorithm (PSO) is
      used as a heuristic optimization method to find the best distribution of effort
      needed to establish an efficient healthcare collaborative network. 

PMID- 25854668
TI  - Three-dimensional image fusion across PET+MRI modalities based on the approach of
      characteristic coregistration.
AB  - BACKGROUND AND AIMS: Because there is no complete three-dimensional (3D) hybrid
      detector integrated PET+MRI internationally, this study aims to investigate a
      registration approach for a two-dimensional (2D) hybrid based on characteristic
      localization to achieve a 3D fusion from the images of PET and MRI as a whole.
      METHODS: A cubic-oriented scheme of "9-point and 3-plane" for a coregistration
      design was verified to be geometrically practical. Through 3D reconstruction and
      virtual dissection, human internal feature points were sorted to combine with
      preselected external feature points for matching process. By following the
      procedure of feature extraction and image mapping, the processes of "picking
      points to form planes" and "picking planes for segmentation" were executed.
      Eventually, the image fusion was implemented at the real-time workstation Mimics
      based on auto-fuse techniques called "information exchange" and "signal overlay".
      RESULTS: A complementary 3D image across PET+MRI modalities, which simultaneously
      present metabolic activities and anatomic structures, was created with a
      detectable rate of 56%. This is equivalent to the detectable rate of PET+CT or
      MRI+CT with no statistically significant difference, and it facilitates a 3D
      vision that is not yet functional for 2D hybrid imaging. CONCLUSIONS: This cross
      modality fusion is doubtless an essential complement for the existing toolkit of
      a 2D hybrid device. Thus, it would potentially improve the efficiency of
      diagnosis and therapy for oncology.

PMID- 25854669
TI  - Aphthous, celiac disease and other dental disorders in childhood.
AB  - BACKGROUND: Oral conditions and dental disorders are frequent in childhood.
      Recurrent aphthous stomatitis (RAS) is a common inflammatory condition
      characterized by painful recurrent, single or multiple ulcerations of the oral
      mucosa induced by genetic and environmental factors. Celiac disease (CD) is a
      chronic small intestinal immunemediated enteropathy precipitated by exposure to
      dietary gluten in genetically predisposed individuals pathogenetically related to
      oral condition. The aim of the study was to evaluate the different prevalence of
      oral conditions in CD patients compared to a control group. METHODS: From January
      2013 to June 2013, 166 patients, between 2 and 17 years of age and of both
      genders, were examined in order to evaluate the presence and the medical history
      of oral conditions. Clinical features of patients affected by CD were compared
      with those of a control group with similar socio-demographic features. RESULTS:
      We found that the more common lesions in both groups were RAS (69% in CD patients
      vs. 43% in the control group), followed by dental disorders (76% in CD patients
      vs. 65% in the control group). Prevalence of RAS between the two groups was
      significantly different (P<0.0006). Prevalences of caries and dental
      abnormalities were the same in the two groups (45% vs. 45% and 16% vs. 16%
      respectively). CONCLUSIONS: In celiac patients there was a significant higher
      prevalence of RAS compared to a control group. These findings could be possibly
      associated with common pathogenetic mechanisms.

PMID- 25854670
TI  - Treatment and prevention of paronychia using a new combination of topicals:
      report of 30 cases.
AB  - AIM: Moderate and chronic paronychia is a common disease affecting the hand.
      Treatment can be effective but the affection is often recurrent, especially as an
      occupational disease. Moreover, this condition may be complicated by a Candida
      spp or by bacterial infections. Therefore, general preventive measures can be
      useful in maintaining health. The aim of this study was to investigate the
      efficacy and tolerability of a new combination of topical medications in the
      treatment and prevention of moderate and chronic paronychia. This formulation
      includes an insulating polymer (Syn-cell barrier), two topical antifungals
      (octopirox and climbazole) and a molecule with anti-inflammatory activity
      (corticoid-like repair). METHODS: Thirty adult subjects (age, 16-78 years; 24
      females and 6 males) affected by moderate or chronic paronychia, with or without
      nail alterations, were evaluated. Included in the study were patients with
      allergic contact dermatitis (8), irritant contact dermatitis (19), psoriatic
      paronychia (2 patients), lichen planus of the nails (1 patient). Sometimes
      Candida spp or bacteria overlapped with paronychia (16 patients positive for
      Candida spp and 4 patients with bacterial paronychia), sometimes infectious
      paronychia was not associated with dermatitis of the hands. All 30 subjects were
      treated with a new cream formulation, three applications per day for 2 months. In
      8 patients with proven and severe candidiasis of the nails, oral fluconazole 100
      mg was added for 20 days. All patients with bacterial perionyxis took
      clarithromycin 500 mg twice daily for six days. Patients were then followed for 8
      weeks. RESULTS: After two months of treatment, 26 patients responded to therapy.
      In particular, the treatment evaluation at the end of the follow-up period showed
      a clinical cure in 46.6% (14 patients), improvement in 40% (12 patients), and
      failure in 13.4% (4 patients). There was a side effect (moderate skin irritation)
      in 2 patients, but the drug was not discontinued. CONCLUSION: Results of the
      present study, based on its safety, effectiveness and innovative features,
      indicate that this combination of topical cream may be considered as a new
      alternative for treatment and prevention of paronychia, especially in case of
      occupational hand disease where prolonged treatment and continuous prevention are
      needed.

PMID- 25854671
TI  - Skin and brain: itch and psychiatric disorders.
AB  - Skin diseases (atopic eczema, psoriasis, idiopathic urticaria), systemic diseases
      (chronic hepatic or renal failure, morbus Hodgkin, diabetes mellitus) and
      psychiatric disorders (obsessive compulsive disorders, depression, delusions of
      parasitosis) can occur with itching. The aim of this review is to clarify the
      link between pruritus and psychiatric morbidity and emphasize the importance of a
      psychiatric consultation for patients with a chronic itching, without a skin
      disease. In the last years, there is a growing awareness regarding psychogenic
      itch, although these types of itch are significantly less studied in comparison
      to other types of pruritus. Psychogenic pruritus is usually a diagnosis of
      exclusion. There are not controlled studies about treatment of psychogenic itch,
      but the same drugs prescribed for neuropathic pain, depression, and anxiety are
      used. There is a strong association between pruritus and psyche; so, it is
      important that the dermatologist evaluates psychosomatic dimension. According to
      the analysis of scientific literature and our clinical experience, pruritus seems
      to be a rather common phenomenon in patients suffering from depression. Future
      works should explain the basis of psychopathology of chronic itching thanks to
      studies of selected groups of patients with a particular type of chronic itching,
      highlighting the clinical features to establish appropriate and individual
      targeted care, based on the several types of pruritus. Some questions still
      unanswered could be clarified in this way. It is really important to decrease the
      symptoms "itching", because the quality of life of the patient will be improved,
      but the goal is to identify the underlying mechanisms of itch and establish a
      targeted therapy, depending on the biological changes and the underlying disease.

PMID- 25854672
TI  - Plasticity of listeriolysin O pores and its regulation by pH and unique histidine
      [corrected].
AB  - Pore formation of cellular membranes is an ancient mechanism of bacterial
      pathogenesis that allows efficient damaging of target cells. Several mechanisms
      have been described, however, relatively little is known about the assembly and
      properties of pores. Listeriolysin O (LLO) is a pH-regulated cholesterol
      dependent cytolysin from the intracellular pathogen Listeria monocytogenes, which
      forms transmembrane beta-barrel pores. Here we report that the assembly of LLO
      pores is rapid and efficient irrespective of pH. While pore diameters at the
      membrane surface are comparable at either pH 5.5 or 7.4, the distribution of pore
      conductances is significantly pH-dependent. This is directed by the unique
      residue H311, which is also important for the conformational stability of the LLO
      monomer and the rate of pore formation. The functional pores exhibit variations
      in height profiles and can reconfigure significantly by merging to other full
      pores or arcs. Our results indicate significant plasticity of large beta-barrel
      pores, controlled by environmental cues like pH. 

PMID- 25854673
TI  - Latent profile analysis and principal axis factoring of the DSM-5 dissociative
      subtype.
AB  - OBJECTIVE: A dissociative subtype has been recognized based on the presence of
      experiences of depersonalization and derealization in relation to DSM-IV
      posttraumatic stress disorder (PTSD). However, the dissociative subtype has not
      been assessed in a community sample in relation to the revised DSM-5 PTSD
      criteria. Moreover, the 20-item PTSD Checklist for DSM-5 (PCL-5) currently does
      not assess depersonalization and derealization. METHOD: We therefore evaluated
      two items for assessing depersonalization and derealization in 557 participants
      recruited online who endorsed PTSD symptoms of at least moderate severity on the
      PCL-5. RESULTS: A five-class solution identified two PTSD classes who endorsed
      dissociative experiences associated with either 1) severe or 2) moderate PTSD
      symptom severity (D-PTSD classes). Those in the severe dissociative class were
      particularly likely to endorse histories of childhood physical and sexual abuse.
      A principal axis factor analysis of the symptom list identified six latent
      variables: 1) Reexperiencing, 2) Emotional Numbing/Anhedonia, 3) Dissociation, 4)
      Negative Alterations in Cognition & Mood, 5) Avoidance, and 6) Hyperarousal.
      CONCLUSIONS: The present results further support the presence of a dissociative
      subtype within the DSM-5 criteria for PTSD.

PMID- 25854675
TI  - Effect of Trigonella foenum graecum L on the Activities of Antioxidant Enzyme and
      Their Expression in Tissues of Alloxan-Induced Diabetic Rats.
AB  - Diabetes is a life-threatening metabolic disorder. This study was undertaken to
      evaluate the antihyperglycemic and antioxidative potential of seed powder of
      Trigonella foenum-graecum L in alloxan (55 mg/kg) induced diabetic rats. The
      results obtained showed that extensive oxidative stress is generated in tissues
      of diabetic rats as evidenced by increased production of hydrogen peroxide,
      increased accumulation of malondialdehyde (MDA) and 4-hydroxynonanal (4HNE) and
      decreased activities of superoxide dismutase (SOD), glutathione peroxidase (GPx),
      and catalase (CAT) in tissues of diabetic rats. It was observed that the
      transcription of genes of SOD, GPx, and CAT was also significantly decreased when
      compared with control. Treatment of Trigonella for 15 days to diabetic rats
      showed hypoglycemic effect and improved the altered levels of H2O2, MDA, and
      4HNE, the activities of SOD, GPx, and CAT as well as transcription of these genes
      in the liver and the brain of diabetic rats. 

PMID- 25854674
TI  - Restoring large-scale brain networks in PTSD and related disorders: a proposal
      for neuroscientifically-informed treatment interventions.
AB  - BACKGROUND: Three intrinsic connectivity networks in the brain, namely the
      central executive, salience, and default mode networks, have been identified as
      crucial to the understanding of higher cognitive functioning, and the functioning
      of these networks has been suggested to be impaired in psychopathology, including
      posttraumatic stress disorder (PTSD). OBJECTIVE: 1) To describe three main large
      scale networks of the human brain; 2) to discuss the functioning of these neural
      networks in PTSD and related symptoms; and 3) to offer hypotheses for
      neuroscientifically-informed interventions based on treating the abnormalities
      observed in these neural networks in PTSD and related disorders. METHODS:
      Literature relevant to this commentary was reviewed. RESULTS: Increasing evidence
      for altered functioning of the central executive, salience, and default mode
      networks in PTSD has been demonstrated. We suggest that each network is
      associated with specific clinical symptoms observed in PTSD, including cognitive
      dysfunction (central executive network), increased and decreased
      arousal/interoception (salience network), and an altered sense of self (default
      mode network). Specific testable neuroscientifically-informed treatments aimed to
      restore each of these neural networks and related clinical dysfunction are
      proposed. CONCLUSIONS: Neuroscientifically-informed treatment interventions will
      be essential to future research agendas aimed at targeting specific PTSD and
      related symptoms.

PMID- 25854676
TI  - Influence of Verapamil on Pharmacokinetics of Triptolide in Rats.
AB  - The aim of this study was to investigate the role of P-glycoprotein (P-gp) in the
      intestinal absorption of triptolide. In this research, the bidirectional
      transport of triptolide across Caco-2 cells was studied in vitro. Moreover, the
      pharmacokinetic profiles of orally administered triptolide with and without
      pretreatment with verapamil were determined in rats. A markedly higher transport
      of triptolide across Caco-2 cells was observed in the basolateral-to-apical
      direction and was abrogated in the presence of the P-gp inhibitor, verapamil. The
      result indicated that P-gp might be involved in the absorption of triptolide.
      When the rats were pretreated with verapamil, the C max of triptolide increased
      from 423.01 +/- 19.59 to 565.33 +/- 20.27 ng/mL (33.6 %), and the AUC0-6 h
      increased by approximately 57 % when co-administered with verapamil. It was
      demonstrated that P-gp was involved in the transport of triptolide, which might
      exhibit a role in limiting its absorption and attenuating the toxicity of
      triptolide. 

PMID- 25854678
TI  - Direct lineage conversion of astrocytes to induced neural stem cells or neurons.
AB  - Since the generation of induced pluripotent stem cells in 2006, cellular
      reprogramming has attracted increasing attention as a revolutionary strategy for
      cell replacement therapy. Recent advances have revealed that somatic cells can be
      directly converted into other mature cell types, which eliminates the risk of
      neoplasia and the generation of undesired cell types. Astrocytes become reactive
      and undergo proliferation, which hampers axon regeneration following injury,
      stroke, and neurodegenerative diseases. An emerging technique to directly
      reprogram astrocytes into induced neural stem cells (iNSCs) and induced neurons
      (iNs) by neural fate determinants brings potential hope to cell replacement
      therapy for the above neurological problems. Here, we discuss the development of
      direct reprogramming of various cell types into iNs and iNSCs, then detail
      astrocyte-derived iNSCs and iNs in vivo and in vitro. Finally, we highlight the
      unsolved challenges and opportunities for improvement. 

PMID- 25854679
TI  - Zinc binds to and directly inhibits protein phosphatase 2A in vitro.
AB  - Zinc induces protein phosphatase 2A (PP2A) inactivation and tau
      hyperphosphorylation through PP2A (tyrosine 307) phosphorylation in cells and the
      brain, but whether Zn(2+) has a direct inhibitory effect on PP2A is not clear.
      Here we explored the effect of Zn(2+) on PP2A and their direct interaction in
      vitro. The results showed that Zn(2+) mimicked the inhibitory effect of okadaic
      acid on protein phosphatase and prevented tau dephosphorylation in N2a cell
      lysates. PP2A activity assays indicated that a low concentration (10 MUmol/L) of
      Zn(2+) inhibited PP2A directly. Further Zn(2+)-IDA-agarose affinity binding
      assays showed that Zn(2+) bound to and inhibited PP2Ac(51-270) but not PP2Ac(1
      50) or PP2Ac(271-309). Taken together, Zn(2+) inhibits PP2A directly through
      binding to PP2Ac(51-270) in vitro. 

PMID- 25854680
TI  - How to interpret multidimensional quality of life questionnaires for patients
      with schizophrenia?
AB  - PURPOSE: The classification of patients into distinct categories of quality of
      life (QoL) levels may be useful for clinicians to interpret QoL scores from
      multidimensional questionnaires. The aim of this study had been to define
      clusters of QoL levels from a specific multidimensional questionnaire (SQoL18)
      for patients with schizophrenia by using a new method of interpretable clustering
      and to test its validity regarding socio-demographic, clinical, and QoL
      information. METHODS: In this multicentre cross-sectional study, patients with
      schizophrenia have been classified using a hierarchical top-down method called
      clustering using unsupervised binary trees (CUBT). A three-group structure has
      been employed to define QoL levels as "high", "moderate", or "low". Socio
      demographic, clinical, and QoL data have been compared between the three clusters
      to ensure their clinical relevance. RESULTS: A total of 514 patients have been
      analysed: 78 are classified as "low", 265 as "moderate", and 171 as "high". The
      clustering shows satisfactory statistical properties, including reproducibility
      (using bootstrap analysis) and discriminancy (using factor analysis). The three
      clusters consistently differentiate patients. As expected, individuals in the
      "high" QoL level cluster report the lowest scores on the Positive and Negative
      Syndrome Scale (p = 0.01) and the Calgary Depression Scale (p < 0.01), and the
      highest scores on the Global Assessment of Functioning (p < 0.03), the SF36 (p <
      0.01), the EuroQol (p < 0.01), and the Quality of Life Inventory (p < 0.01).
      CONCLUSION: Given the ease with which this method can be applied, classification
      using CUBT may be useful for facilitating the interpretation of QoL scores in
      clinical practice.

PMID- 25854681
TI  - Identification of endogenous metabolites in human sperm cells using proton
      nuclear magnetic resonance ((1) H-NMR) spectroscopy and gas chromatography-mass
      spectrometry (GC-MS).
AB  - The objective of this study was to contribute to the first comprehensive
      metabolomic characterization of the human sperm cell through the application of
      two untargeted platforms based on proton nuclear magnetic resonance ((1) H-NMR)
      spectroscopy and gas chromatography coupled to mass spectrometry (GC-MS). Using
      these two complementary strategies, we were able to identify a total of 69
      metabolites, of which 42 were identified using NMR, 27 using GC-MS and 4 by both
      techniques. The identity of some of these metabolites was further confirmed by
      two-dimensional (1) H-(1) H homonuclear correlation spectroscopy (COSY) and (1) H
      (13) C heteronuclear single-quantum correlation (HSQC) spectroscopy. Most of the
      metabolites identified are reported here for the first time in mature human
      spermatozoa. The relationship between the metabolites identified and the
      previously reported sperm proteome was also explored. Interestingly,
      overrepresented pathways included not only the metabolism of carbohydrates, but
      also of lipids and lipoproteins. Of note, a large number of the metabolites
      identified belonged to the amino acids, peptides and analogues super class. The
      identification of this initial set of metabolites represents an important first
      step to further study their function in male gamete physiology and to explore
      potential reasons for dysfunction in future studies. We also demonstrate that the
      application of NMR and MS provides complementary results, thus constituting a
      promising strategy towards the completion of the human sperm cell metabolome. 

PMID- 25854682
TI  - Intrauterine device use and the risk of pre-eclampsia: a case-control study.
AB  - OBJECTIVE: To determine the association between intrauterine device (IUD) use,
      timing of removal prior to pregnancy, and the risk of pre-eclampsia. DESIGN: A
      case-control study within the Clinical Practice Research Datalink, UK. SETTING:
      Medical record database in the UK. SAMPLE: Cases of pre-eclampsia (n = 2744) were
      identified among pregnancies resulting in singleton deliveries from 1993 to 2010.
      Four controls, or pregnancies unaffected by pre-eclampsia, were matched to each
      case on maternal age, general practice, and year of delivery. METHODS: Data on
      IUD use were obtained from patient records. The odds ratios (ORs) for the
      association between IUD and pre-eclampsia were adjusted for covariates identified
      a priori, and analyses were stratified by BMI and number of prior deliveries.
      MAIN OUTCOME MEASURES: Odds ratios (95% confidence intervals, 95% CIs) of pre
      eclampsia in pregnancies among women with a history of IUD use, compared with
      women without a history of IUD use. RESULTS: Prior IUD use was associated with a
      reduced risk of pre-eclampsia (OR 0.76; 95% CI 0.58-0.98). The timing of removal
      in relation to the start of pregnancy showed an inverse association, with shorter
      intervals associated with a larger decrease in risk of pre-eclampsia. IUD removal
      within a year prior to pregnancy had an OR of 0.68 (95% CI 0.46-1.00). Among
      women with a prior delivery, the association between IUD use and pre-eclampsia
      was null. CONCLUSIONS: Intrauterine device use is associated with a small
      decreased risk of pre-eclampsia, specifically if removed within the year prior to
      conception. TWEETABLE ABSTRACT: A case-control study of pregnancies in the UK
      suggests a reduced risk of pre-eclampsia for former IUD users.

PMID- 25854683
TI  - A species-specific nucleosomal signature defines a periodic distribution of amino
      acids in proteins.
AB  - Nucleosomes are the basic structural units of chromatin. Most of the yeast genome
      is organized in a pattern of positioned nucleosomes that is stably maintained
      under a wide range of physiological conditions. In this work, we have searched
      for sequence determinants associated with positioned nucleosomes in four species
      of fission and budding yeasts. We show that mononucleosomal DNA follows a highly
      structured base composition pattern, which differs among species despite the high
      degree of histone conservation. These nucleosomal signatures are present in
      transcribed and non-transcribed regions across the genome. In the case of open
      reading frames, they correctly predict the relative distribution of codons on
      mononucleosomal DNA, and they also determine a periodicity in the average
      distribution of amino acids along the proteins. These results establish a direct
      and species-specific connection between the position of each codon around the
      histone octamer and protein composition. 

PMID- 25854685
TI  - The highest utilizers of care: individualized care plans to coordinate care,
      improve healthcare service utilization, and reduce costs at an academic tertiary
      care center.
AB  - BACKGROUND: High utilizers are medically and psychosocially complex, have high
      rates of emergency department (ED) visits and hospital admissions, and contribute
      to rising healthcare costs. OBJECTIVE: Develop individualized care plans to
      reduce unnecessary healthcare service utilization and hospital costs for complex,
      high utilizers of inpatient and ED care. DESIGN: Quality-improvement intervention
      with a retrospective pre/post intervention analysis. SETTING: Nine hundred twenty
      four-bed tertiary academic medical center. PATIENTS: Twenty-four medically and
      psychosocially complex patients with the highest rates of inpatient admissions
      and ED visits from August 1, 2012 to August 31, 2013. INTERVENTION: A
      multidisciplinary team developed individualized care plans integrated into our
      electronic medical record (EMR) that summarize patient histories, utilization
      patterns, and management strategies. MEASUREMENTS: Primary outcomes included
      inpatient admissions, ED visits, and corresponding variable direct costs 6 and 12
      months after care-plan implementation. Secondary outcomes include inpatient
      length of stay (LOS) and 30-day readmissions. RESULTS: Hospital admissions
      decreased by 56% (P < 0.001) and 50.5% (P = 0.003), 6 and 12 months after care
      plan implementation. Thirty-day readmissions decreased by 66% (P < 0.001) and
      51.5% (P = 0.002), 6 and 12 months after care-plan implementation. ED visits, ED
      costs, and inpatient LOS did not significantly change. Inpatient variable direct
      costs were reduced by 47.7% (P = 0.001) and 35.8% (P = 0.052), 6 and 12 months
      after care-plan implementation. CONCLUSIONS: Individualized care plans developed
      by a multidisciplinary team and integrated with the existing healthcare workforce
      and EMR reduce hospital admissions, 30-day readmissions, and hospital costs for
      complex, high-utilizing patients.

PMID- 25854686
TI  - Pipeline embolization for definitive endoluminal reconstruction of blister-type
      carotid aneurysms after clip wrapping.
AB  - BACKGROUND: Ruptured blister aneurysms of the carotid artery are difficult to
      safely treat. We present a novel strategy of microsurgical clip wrapping of
      internal carotid artery blister aneurysms in the setting of acute rupture,
      followed by delayed placement of a pipeline embolization device for definitive
      treatment. CLINICAL PRESENTATION: We present two cases of ruptured blister
      aneurysms of the internal carotid artery treated by wrapping of the diseased
      segment of the vessel, followed by delayed deployment of a flow diverting stent
      once the patient was out of the vasospasm window but during the same
      hospitalization. RESULTS: Clip wrapping followed by flow diversion in a delayed
      fashion results in anatomic remodeling of the diseased artery without a high
      morbidity. CONCLUSIONS: A combined approach of acute surgical stabilization
      followed by definitive endovascular reconstruction may reduce hemorrhagic
      complications while improving long term treatment durability.

PMID- 25854684
TI  - The peroxisomal protein import machinery displays a preference for monomeric
      substrates.
AB  - Peroxisomal matrix proteins are synthesized on cytosolic ribosomes and
      transported by the shuttling receptor PEX5 to the peroxisomal membrane
      docking/translocation machinery, where they are translocated into the organelle
      matrix. Under certain experimental conditions this protein import machinery has
      the remarkable capacity to accept already oligomerized proteins, a property that
      has heavily influenced current models on the mechanism of peroxisomal protein
      import. However, whether or not oligomeric proteins are really the best and most
      frequent clients of this machinery remain unclear. In this work, we present three
      lines of evidence suggesting that the peroxisomal import machinery displays a
      preference for monomeric proteins. First, in agreement with previous findings on
      catalase, we show that PEX5 binds newly synthesized (monomeric) acyl-CoA oxidase
      1 (ACOX1) and urate oxidase (UOX), potently inhibiting their oligomerization.
      Second, in vitro import experiments suggest that monomeric ACOX1 and UOX are
      better peroxisomal import substrates than the corresponding oligomeric forms.
      Finally, we provide data strongly suggesting that although ACOX1 lacking a
      peroxisomal targeting signal can be imported into peroxisomes when co-expressed
      with ACOX1 containing its targeting signal, this import pathway is inefficient. 

PMID- 25854687
TI  - Monotherapy with stenting in subarachnoid hemorrhage (SAH) after middle cerebral
      artery dissection.
AB  - Isolated middle cerebral artery dissection is a rare clinical entity, with
      descriptions limited to a few case reports and case series. Symptomatic
      dissection in the anterior circulation can present as an ischemic stroke in a
      young population; however, it is rarely associated with subarachnoid hemorrhage.
      We describe a young patient who presented with acute headache from a subarachnoid
      hemorrhage that was ultimately determined to be due to a vascular dissection in
      the middle cerebral artery. The initial angiogram showed vascular irregularities
      in this area with stenosis. Repeat imaging 4 days after presentation identified a
      pseudoaneurysm proximal to the stenosis. The patient was successfully treated
      with a self-expanding nitinol stent and followed up with serial angiography
      during postoperative recovery in the hospital; additional angiograms were
      performed approximately 1 and 6 months after treatment. Serial angiograms
      demonstrated incremental healing of the dissection. The patient was discharged
      and remains neurologically intact at the 6-month follow-up. 

PMID- 25854688
TI  - Venous sinus stenting for idiopathic intracranial hypertension is not associated
      with cortical venous occlusion.
AB  - BACKGROUND: The effect of dural venous sinus stenting has been investigated for
      the treatment of idiopathic intracranial hypertension (IIH) but the effect of
      stenting on the long-term patency of the cortical draining veins, especially the
      vein of Labbe (VOL), remains unknown. METHODS: We reviewed our database of 38
      patients with IIH with 41 stented dural venous sinuses between October 2006 and
      December 2014. Demographic, clinical, and radiological data were reviewed. Follow
      up catheter angiographic data were included when available. RESULTS: Stent
      placement spanned the ostium of the VOL in 35 patients (92.1%), with no immediate
      effect on the drainage of the VOL. Follow-up angiography (mean 35.1 months, range
      1.7-80.7 months) was available in 24 patients, 21 of whom had stents spanning the
      VOL ostium. The VOL remained patent without occlusion or drainage alteration in
      all 21 patients. There were no immediate or long-term intracranial complications.
      CONCLUSIONS: Dural venous sinus stenting for patients with IIH does not affect
      the immediate or long-term patency of the VOL and is not associated with
      intracranial complications.

PMID- 25854689
TI  - Critical role of eukaryotic elongation factor 1 alpha 1 (EEF1A1) in avian
      reovirus sigma-C-induced apoptosis and inhibition of viral growth.
AB  - Avian reovirus (ARV) causes viral arthritis, chronic respiratory diseases,
      retarded growth and malabsorption syndrome. It is well established that the ARV
      sigma-C protein induces apoptosis in host cells. However, the underlying
      molecular mechanism of this induction is still unclear. We report here the
      identification of eukaryotic elongation factor 1 alpha 1 (EEF1A1) as the
      interacting partner of sigmaC. We found that sigmaC-induced apoptosis in DF-1
      cells could be completely abolished by knockdown of EEF1A1 by siRNA. Furthermore,
      knockdown of EEF1A1 markedly reduced ARV-induced apoptosis associated with
      decreased caspase-9 and -3 activation and cytochrome C release, leading to
      increased ARV growth in host cells. Thus, EEF1A1 plays a critical role in sigmaC
      induced apoptosis and inhibition of viral growth.

PMID- 25854690
TI  - Molecular characterization of a novel amalgavirus from the entomopathogenic
      fungus Beauveria bassiana.
AB  - Beauveria bassiana is a ubiquitous entomopathogen infecting hundreds of insect
      species. We have determined the genomic organization and the complete nucleotide
      sequence of a novel virus isolated from the isolate A24 of B. bassiana.
      Phylogenetic analysis of the polymerase gene reveals that the virus, tentatively
      named Beauveria bassiana virus 1, belongs to the family Amalgaviridae and
      represents a distinct lineage of amalgaviruses infecting fungi.

PMID- 25854691
TI  - Adsorption of chemically synthesized mussel adhesive peptide sequences containing
      DOPA on stainless steel.
AB  - The adsorption of proteins at solid-liquid interfaces is important in biosensor
      and biomaterial applications. Marine mussels affix themselves to surfaces using a
      highly cross-linked, protein-based adhesive containing a high proportion of L-3,4
      dihydroxyphenylalanine (DOPA) residues. In this work, the effect of DOPA residues
      on protein adhesion on stainless steel surfaces was studied using a quartz
      crystal microbalance with dissipation system. The adsorption of two repetitive
      peptide motifs, KGYKYYGGSS and KGYKYY, from the mussel Mytilus edulis foot
      protein 5 on stainless steel was studied before and after chemo-enzymatic
      modification of tyrosine residues to DOPA using mushroom tyrosinase. Conversion
      from tyrosine to DOPA, evaluated by HPLC, was in the range 70-99%. DOPA-modified
      sequences showed fourfold greater adhesion than unmodified M. edulis foot protein
      5 motifs.

PMID- 25854692
TI  - Acute kidney injury after percutaneous coronary intervention: Rationale of the
      AKI-MATRIX (acute kidney injury-minimizing adverse hemorrhagic events by
      TRansradial access site and systemic implementation of angioX) sub-study.
AB  - Acute kidney injury (AKI) is an important complication of both diagnostic cardiac
      catheterization and percutaneous coronary intervention (PCI). A large body of
      evidence supports that AKI is related to volume of contrast used. Despite several
      measures are available to reduce the impact of contrast media on AKI, its
      incidence remains significant as other mechanisms of renal damage are involved. A
      new paradigm is established according to which bleeding prevention is at least as
      important as preventing recurrent ischemic events in the management of patients
      with acute coronary syndromes (ACS) undergoing an invasive approach.
      Periprocedural bleeding, which is consistently reduced by radial approach, is
      emerging as a risk factor for the development of AKI. Therefore, the role of
      vascular access as a measure to prevent AKI needs to be systematically assessed
      in randomized studies. To date, no prospective comparison on renal outcomes has
      been carried out in randomized trials between radial and femoral approach. The
      Minimizing Adverse hemorrhagic events by TRansradial access site and systemic
      Implementation of AngioX (MATRIX) trial (ClinicalTrials.gov identifier:
      NCT01433627) has been designed to test whether to minimize bleeding events by
      using radial access and bivalirudin, across the whole spectrum of patients with
      ACS undergoing PCI, will result in improved outcomes with respect to both
      ischemic and bleeding complications. The AKI-MATRIX sub-study will provide a
      unique opportunity to assess whether the advantages of radial approach may even
      contribute to the reduction of the risk of AKI in patients with ACS.

PMID- 25854694
TI  - School Health Services for Children With Special Health Care Needs in California.
AB  - Children with special health care needs (CSHCN) are at risk for school failure
      when their health needs are not met. Current studies have identified a strong
      connection between school success and health. This study attempted to determine
      (a) how schools meet the direct service health needs of children and (b) who
      provides those services. The study used the following two methods: (a) analysis
      of administrative data from the California Basic Educational Data System and (b)
      a cross-sectional online survey of 446 practicing California school nurses. Only
      43% of California's school districts employ school nurses. Unlicensed school
      personnel with a variety of unregulated training provide school health services.
      There is a lack of identification of CSHCN, and communication barriers impair the
      ability to deliver care. Study results indicate that California invests minimally
      in school health services. 

PMID- 25854693
TI  - Above-belowground interactions govern the course and impact of biological
      invasions.
AB  - Introduction of exotic organisms that subsequently become invasive is considered
      a serious threat to global biodiversity, and both scientists and nature
      conservationists attempt to find explanations and means to meet this challenge.
      This requires a thorough analysis of the invasion phenomenon in an evolutionary
      and ecological context; in the case of invasive plants, we must have a major
      focus on above-belowground interactions. Thus, we discuss different theories that
      have been proposed to explain the course of invasions through interactions
      between plants and soil organisms. Further, a thorough analysis of invasion must
      include a temporal context. Invasions will typically include an initial acute
      phase, where the invader expands its territory and a later chronic phase where
      equilibrium is re-established. Many studies fail to make this distinction, which
      is unfortunate as it makes it impossible to thoroughly understand the invasion of
      focus. Thus, we claim that invasions fall into two broad categories. Some
      invasions irreversibly change pools and pathways of matter and energy in the
      invaded system; even if the abundance of the invader is reduced or it is
      completely removed, the system will not return to its former state. We use
      earthworm invasion in North America as a particular conspicuous example of
      invasive species that irreversibly change ecosystems. However, invasions may also
      be reversible, where the exotic organism dominates the system for a period, but
      in the longer term it either disappears, declines or its negative impact
      decreases. If the fundamental ecosystem structure and flows of energy and matter
      have not been changed, the system will return to a state not principally
      different from the original. 

PMID- 25854695
TI  - A Cu-free clickable fluorescent probe for intracellular targeting of small
      biomolecules.
AB  - We synthesized a novel cyclooctyne-based clickable fluorescent probe with
      versatile properties such as high cell-membrane permeability and free
      diffusibility in the cell. Our probe "FC-DBCO" was conjugated to an azide
      modified mannose via a Cu-free click reaction in living HeLa cells and displayed
      intracellular specific fluorescence imaging with low background signals. 

PMID- 25854696
TI  - FGF19 promotes progression of prostate cancer.
AB  - BACKGROUND: Fibroblast growth factor (FGF) signaling pathways have been reported
      to play important roles in prostate cancer (PCa) progression. FGF19 is one of a
      subfamily of FGFs that circulate in serum and act in an endocrine manner. Our
      objective was to investigate its role in the progression of PCa. METHODS: The
      effect of FGF19 on the proliferation and epithelial-mesenchymal transition of
      LNCaP and PC3 cells was examined using MTT assay and Western blotting. Serum
      concentration of FGF19 was measured by ELISA in 209 patients with PCa, and the
      association between clinicopathological features and the presence of FGF19
      positive cells in tissues derived from 155 patients who undergone radical
      prostatectomy was investigated. RESULTS: Under androgen-deprived conditions
      achieved by incubation in medium with FGF19, the expression of N-cadherin in
      LNCaP cells was enhanced, that of E-cadherin and caspase 3 was suppressed, and
      the viability of LNCaP and PC3 cells was significantly enhanced. Significantly
      higher levels of PSA were recorded in the group determined by
      immunohistochemistry staining to be FGF19-positive (P = 0.0046). The 5-year
      biochemical recurrence-free survival rate after radical prostatectomy was 46.4%
      in the FGF19-positive group and 70.0% in the FGF19-negative group (P = 0.0027).
      In multivariate analysis, the presence of FGF19-positive tissues was an
      independent factor for worse prognosis after radical prostatectomy (P = 0.0052).
      Serum FGF19 levels in high Gleason grade group were higher than that in low
      Gleason grade group (P = 0.0009). CONCLUSIONS: FGF19 might be associated with
      biochemical recurrence after radical prostatectomy by promoting cell
      proliferation and epithelial-mesenchymal transition of PCa.

PMID- 25854698
TI  - Analyzing the effectiveness of using branchial NKA activity as a biomarker for
      assessing waterborne copper toxicity in tilapia (Oreochromis mossambicus): A
      damage-based modeling approach.
AB  - Branchial Na(+)-K(+)-ATPase (NKA) activity has been suggested as a promising
      biomarker for assessing metal stress in aquatic organisms. However, studies that
      systematically show the effectiveness of using NKA activity to detect metal
      exposure and toxicity at the individual level are limited. In this study, we
      aimed to determine whether branchial NKA activity mechanistically responds to the
      accumulation of waterborne copper (Cu) and accounts for observed toxicity over
      time under environmentally-relevant and aquafarming Cu exposure levels (0.2, 1
      and 2 mg L(-1)). Temporal trends in Cu accumulation and the corresponding
      responses of branchial NKA activity resulting from Cu exposure were investigated
      in laboratory experiments conducted on juvenile tilapia (Oreochromis
      mossambicus), a freshwater teleost that shows potential as a bioindicator of real
      time and historical metal pollution. We used the process-based damage assessment
      model (DAM) to inspect the time course of Cu toxicity by integrating the
      compensation process between Cu-induced inhibition and repair of branchial NKA
      activity. NKA activity acted as a sensitive biomarker for Cu exposure and
      accumulation in tilapia, which showed induced impairment of osmoregulation and
      lethality when they were exposed to environmentally relevant levels (0.2 mg L(
      1)), but not to higher exposure levels (1 and 2 mg L(-1)) in aquaculture farms or
      contaminated aquatic ecosystems. This study highlights the benefits and
      limitations of using branchial NKA activity as a sensitive biomarker to assess
      the health status of a fish population and its ecosystem.

PMID- 25854697
TI  - Molecular basis of oxidative stress in gouty arthropathy.
AB  - Gout is a disorder of urate metabolism in which persistent high urate levels in
      the extracellular fluids result in the deposition of monosodium urate (MSU)
      crystal in joints and periarticular tissues. In recent years, this disease
      represents an increasingly common health problem, so the pace of investigation in
      the field has accelerated tremendously. New research advances in the pathogenesis
      of hyperuricemia and in the understanding of how MSU crystals induce an acute
      gouty attack have been focused in this review on the processes of inflammation
      and involvement of the innate immune response; in addition, we discuss new
      knowledge about the role of the reactive oxygen species in establishing oxidative
      stress in MSU crystal-induced arthritis. 

PMID- 25854699
TI  - Ecological modelling and toxicity data coupled to assess population recovery of
      marine amphipod Gammarus locusta: Application to disturbance by chronic exposure
      to aniline.
AB  - A population agent-based model of marine amphipod Gammarus locusta was designed
      and implemented as a basis for ecological risk assessment of chemical pollutants
      impairing life-history traits at the individual level. We further used the model
      to assess the toxic effects of aniline (a priority hazardous and noxious
      substance, HNS) on amphipod populations using empirically-built dose-response
      functions derived from a chronic bioassay that we previously performed with this
      species. We observed a significant toxicant-induced mortality and adverse effects
      in reproductive performance (reduction of newborn production) in G. locusta at
      the individual level. Coupling the population model with the toxicological data
      from the chronic bioassay allowed the projection of the ecological costs
      associated with exposure to aniline that might occur in wild populations. Model
      simulations with different scenarios indicated that even low level prolonged
      exposure to the HNS aniline can have significant long-term impacts on G. locusta
      population abundance, until the impacted population returns to undisturbed
      levels. This approach may be a useful complement in ecotoxicological studies of
      chemical pollution to transfer individual-collected data to ecological-relevant
      levels. 

PMID- 25854701
TI  - Chemical genetic approach identifies microtubule affinity-regulating kinase 1 as
      a leucine-rich repeat kinase 2 substrate.
AB  - Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of
      autosomal-dominant forms of Parkinson's disease. LRRK2 is a modular, multidomain
      protein containing 2 enzymatic domains, including a kinase domain, as well as
      several protein-protein interaction domains, pointing to a role in cellular
      signaling. Although enormous efforts have been made, the exact pathophysiologic
      mechanisms of LRRK2 are still not completely known. In this study, we used a
      chemical genetics approach to identify LRRK2 substrates from mouse brain. This
      approach allows the identification of substrates of 1 particular kinase in a
      complex cellular environment. Several of the identified peptides are involved in
      the regulation of microtubule (MT) dynamics, including microtubule-associating
      protein (MAP)/microtubule affinity-regulating kinase 1 (MARK1). MARK1 is a
      serine/threonine kinase known to phosphorylate MT-binding proteins such as Tau,
      MAP2, and MAP4 at KXGS motifs leading to MT destabilization. In vitro kinase
      assays and metabolic-labeling experiments in living cells confirmed MARK1 as an
      LRRK2 substrate. Moreover, we also showed that LRRK2 and MARK1 are interacting in
      eukaryotic cells. Our findings contribute to the identification of physiologic
      LRRK2 substrates and point to a potential mechanism explaining the reported
      effects of LRRK2 on neurite morphology.

PMID- 25854702
TI  - Protein motions and dynamic effects in enzyme catalysis.
AB  - The role of protein motions in promoting the chemical step of enzyme catalysed
      reactions remains a subject of considerable debate. Here, a unified view of the
      role of protein dynamics in dihydrofolate reductase catalysis is described.
      Recently the role of such motions has been investigated by characterising the
      biophysical properties of isotopically substituted enzymes through a combination
      of experimental and computational analyses. Together with previous work, these
      results suggest that dynamic coupling to the chemical coordinate is detrimental
      to catalysis and may have been selected against during DHFR evolution. The full
      catalytic power of Nature's catalysts appears to depend on finely tuning protein
      motions in each step of the catalytic cycle. 

PMID- 25854700
TI  - Hyperhomocysteinemia suppresses bone marrow CD34+/VEGF receptor 2+ cells and
      inhibits progenitor cell mobilization and homing to injured vasculature-a role of
      beta1-integrin in progenitor cell migration and adhesion.
AB  - Hyperhomocysteinemia (HHcy) impairs re-endothelialization and accelerates
      vascular remodeling. The role of CD34(+)/VEGF receptor (VEGFR) 2(+) progenitor
      cells (PCs) in vascular repair in HHcy is unknown. We studied the effect of HHcy
      on PCs and its role in vascular repair in severe HHcy (~150 MUM), which was
      induced in cystathionine-beta synthase heterozygous mice fed a high-methionine
      diet for 8 weeks. Vascular injury was introduced by carotid air-dry endothelium
      denudation. CD34(+)/VEGFR2(+) cells were examined by flow cytometry. HHcy reduced
      bone marrow (BM) CD34(+)/VEGFR2(+) cells and suppressed replenishment of
      postinjury CD34(+)/VEGFR2(+) cells in peripheral blood (PB). Donor green
      fluorescent protein-positive PC homing to the injured vessel was reduced in HHcy
      after CD34(+) PCs from enhanced green fluorescent protein mice were adoptively
      transferred following carotid injury. CD34(+) PC transfusion partially reversed
      HHcy-suppressed re-endothelialization and HHcy-induced neointimal formation.
      Furthermore, homocysteine (Hcy) inhibited proliferation, adhesion, and migration
      and suppressed beta1-integrin expression and activity in human CD34(+)
      endothelial colony-forming cells (ECFCs) isolated from PBs in a dose-dependent
      manner. A functional-activating beta1-integrin antibody rescued Hcy-suppressed
      adhesion and migration in CD34(+) ECFCs. In conclusion, HHcy reduces BM
      CD34(+)/VEGFR2(+) generation and suppresses CD34(+)/VEGFR2(+) cell mobilization
      and homing to the injured vessel via beta1-integrin inhibition, which partially
      contributes to impaired re-endothelialization and vascular remodeling.

PMID- 25854703
TI  - Cardioprotective effect of hyperthyroidism on the stunned rat heart during
      ischaemia-reperfusion: energetics and role of mitochondria.
AB  - NEW FINDINGS: What is the central question of this study? Hyperthyroidism is a
      cardiac risk factor, but thyroid therapy is used on myocardial stunning. What is
      the consequence of hyperthyroidism for mitochondrial metabolism and Ca(2+)
      handling of the postischaemic stunned heart? What is the main finding and its
      importance? Hyperthyroidism reduced stunning and improved muscle economy of the
      postischaemic rat heart. The activities of the mitochondrial sodium-calcium
      exchanger and mitochondrial K(+) channel in hyperthyroid rat hearts were
      different from those in the euthyroid rat hearts. These findings contribute to
      the understanding of mitochondrial bioenergetics in pathology and support thyroid
      therapy in the stunning induced by ischaemia. Transient ischaemia and
      hyperthyroidism are cardiovascular risk factors. Nevertheless, 3,5,3'
      triiodothyronine/thyroxine therapy has been used to revert myocardial stunning.
      We studied the influence of hyperthyroidism on the role played by mitochondria in
      myocardial stunning consequent to ischaemia-reperfusion. Rats were injected s.c.
      daily with 20 MUg kg(-1) triiodothyronine for 15 days (HpT group). Isolated
      ventricles from either HpT or euthyroid (EuT) rats were perfused in a
      calorimeter, and left intraventricular pressure (in millimetres of mercury) and
      heat release (Ht; in milliwatts per gram) were measured. Stunning was evoked by
      20 min of no-flow ischaemia and 45 min reperfusion. The HpT hearts developed
      higher postischaemic contractile recovery (PICR) and improved total muscle
      economy (P/Ht) with lower diastolic contracture (DeltaLVEDP) than EuT hearts.
      Release of Ca(2+) from the sarcoplasmic reticulum during reperfusion with 10 mm
      caffeine in low-[Na(+) ] Krebs solution evoked a higher contracture in EuT than
      in HpT hearts. Blockade of the mitochondrial sodium-calcium exchanger with
      clonazepam increased DeltaLVEDP and reduced P/Ht and PICR in HpT but not in EuT
      hearts. The clonazepam-induced dysfunction in HpT hearts was reduced by
      ciclosporin, suggesting a dependance on activation of the mitochondrial
      permeability transition pore. Blockade of the mitochondrial Ca(2+) uniporter with
      Ru360 reduced P/Ht and PICR to ~10% in both HpT and EuT hearts. Blockade of
      mitochondrial K(+) channels with 5-hydroxydecanoate increased LVEDP and reduced
      PICR and P/Ht in HpT hearts, while it only increased LVEDP in EuT hearts. The
      results suggest that hyperthyroidism prevents the stunning with high dependence
      on the mitochondrial sodium-calcium exchanger and mitochondrial K(+) channels.
      Both HpT and EuT hearts showed a similar and critical role of the uniporter. The
      HpT hearts have a slow sarcoplasmic reticulum Ca(2+) loss and low mitochondrial
      Ca(2+) uptake.

PMID- 25854705
TI  - The use of residual dipolar coupling for conformational analysis of structurally
      related natural products.
AB  - Determining the conformational preferences of molecules in solution remains a
      considerable challenge. Recently, the use of residual dipolar coupling (RDC)
      analysis has emerged as a key method to address this. Whilst to date the majority
      of the applications have focused on biomolecules including proteins and DNA, the
      use of RDCs for studying small molecules is gaining popularity. Having said that,
      the method continues to develop, and here, we describe an early case study of the
      quantification of conformer populations in small molecules using RDC analysis.
      Having been inspired to study conformational preferences by unexpected
      differences in the NMR spectra and the reactivity of related natural products, we
      showed that the use of more established techniques was unsatisfactory in
      explaining the experimental observations. The use of RDCs provided an improved
      understanding that, following use of methods to quantify conformer populations
      using RDCs, culminated in a rationalisation of the contrasting
      diastereoselectivities observed in a ketone reduction reaction.

PMID- 25854706
TI  - The role of electron donors generated from UV photolysis for accelerating
      pyridine biodegradation.
AB  - Employing an internal circulation baffled biofilm reactor (ICBBR), we evaluated
      the mechanisms by which photolysis accelerated the biodegradation and
      mineralization of pyridine (C5 H5 N), a nitrogen-containing heterocyclic
      compound. We tested the hypothesis that pyridine oxidation is accelerated because
      a key photolysis intermediate, succinate, is as electron donor that promotes the
      initial mono-oxygenation of pyridine. Experimentally, longer photolysis time
      generated more electron-donor products (succinate), which stimulated faster
      pyridine biodegradation. This pattern was confirmed by directly adding succinate,
      and the stimulation effect occurred similarly with addition of the same
      equivalents of acetate and formate. Succinate, whether generated by UV photolysis
      or added directly, also accelerated mono-oxygenation of the first biodegradation
      intermediate, 2-hydroxyl pyridine (2HP). 2HP and pyridine were mutually
      inhibitory in that their mono-oxygenations competed for internal electron donor;
      thus, the addition of any readily biodegradable donor accelerated both mono
      oxygenation steps, as well as mineralization.

PMID- 25854707
TI  - Do nutrients influence bone health? A commentary on new findings in the field.

PMID- 25854708
TI  - Pt NPs immobilized on core-shell magnetite microparticles: novel and highly
      efficient catalysts for the selective aerobic oxidation of ethanol and glycerol
      in water.
AB  - Three core-shell structures were prepared with pyrrole, glucose, and tetraethyl
      orthosilicate (TEOS), respectively, encasing magnetic Fe3O4 microparticles,
      through three different "green" approaches without any toxic solvents. Pt
      nanoparticles (NPs) were immobilized onto these supports with NaBH4 as the
      reducing agent. The as-prepared catalysts were characterized thoroughly by TEM,
      VSM, XRD, FT-IR, ICP, and XPS. As expected, the shells remarkably affected the
      distribution of Pt NPs and catalytic activity. Pt NPs dispersed evenly on the
      surface of Fe3O4@PPy and Fe3O4@C, which were much better than Fe3O4@SiO2. Most
      attractively, the prepared catalysts exhibited better kinetics, higher activity
      and stability than Pt/Fe3O4 and Pt/C for selective oxidation of ethanol to acetic
      acid and glycerol to glyceric acid with molecular oxygen in water. Among them,
      the catalyst with a shell of polypyrrole (PPy) showed the best catalytic
      property, affording yields of 88% and 55%, respectively. Moreover, it could be
      recovered facilely from the reaction mixture and recycled four times without any
      significant loss in activity. 

PMID- 25854704
TI  - Parathyroid hormone: anabolic and catabolic actions on the skeleton.
AB  - Parathyroid hormone (PTH) is essential for the maintenance of calcium homeostasis
      through, in part, its actions to regulate bone remodeling. While PTH stimulates
      both bone formation and bone resorption, the duration and periodicity of exposure
      to PTH governs the net effect on bone mass, that is whether it is catabolic or
      anabolic. PTH receptor signaling in osteoblasts and osteocytes can increase the
      RANKL/OPG ratio, increasing both osteoclast recruitment and osteoclast activity,
      and thereby stimulating bone resorption. In contrast, PTH-induced bone formation
      is explained, at least in part, by its ability to downregulate SOST/sclerostin
      expression in osteocytes, permitting the anabolic Wnt signaling pathway to
      proceed. The two modes of administration of PTH, that is, continuous vs.
      intermittent, can regulate, in bone cells, different sets of genes;
      alternatively, the same sets of genes exposed to PTH in sustained vs. transient
      way, will favor bone resorption or bone formation, respectively. This article
      reviews the effects of PTH on bone cells that lead to these dual catabolic and
      anabolic actions on the skeleton. 

PMID- 25854709
TI  - The features of clearance in recombinant factor IX (BeneFIX((r)) ).
AB  - INTRODUCTION: Dosage adjustment is very important to perform continuous infusion
      (CI) of recombinant factor IX (rFIX) concentrates more effectively and
      economically, and clearance (CL) is strongly related to the infusion rate.
      However, previous reports have shown that the CL of rFIX concentrates varies
      widely (4.2-11.4 mL kg(-1) h(-1) ). AIM: The goal of this study was to gain a
      better understanding of the CL of the rFIX concentrate (BeneFIX((r)) ) to
      precisely set the infusion rate of rFIX concentrates. METHODS: We estimated CLs
      by five different calculation approaches: from area under the blood concentration
      time curve (AUC), from in vivo recovery (IVR) and half-life, from actual FIX
      activity value during CI, and from the simulation by one-compartment model in
      seven patients with haemophilia B. RESULTS: The mean CL calculated from AUC was
      3.8 +/- 0.4 mL kg(-1) h(-1) (range = 3.3-4.3 mL kg(-1) h(-1) ). CONCLUSION: The
      mean CL calculated from IVR and distribution half-life was 4.4 +/- 0.4 mL kg(-1)
      h(-1) (range = 4.0-5.1 mL kg(-1) h(-1) ). The mean CL calculated from IVR and
      terminal half-life was 2.1 +/- 0.5 mL kg(-1) h(-1) (range = 1.7-2.8 mL kg(-1) h(
      1) ). The mean CL during CI was 4.9 +/- 0.6 mL kg(-1) h(-1) (range = 4.2-5.6 mL
      kg(-1) h(-1) ). In addition, when we simulated the theoretical CL using a one
      compartment model, the adjusted mean CL during CI was 4.8 +/- 0.5 mL kg(-1) h(-1)
      (range = 4.0-5.4 mL kg(-1) h(-1) ). The CL obtained from distribution half-life
      was comparable to the CL during CI, while the CL calculated from terminal half
      life did not reflect actual CL. Further, the rFIX concentrate was characterized
      by a one-compartment model under certain conditions.

PMID- 25854710
TI  - Fatty Acid Profiles for Differentiating Growth Medium Formulations Used to
      Culture Bacillus cereus T-strain Spores.
AB  - Microbial biomarkers that indicate aspects of an organism's growth conditions are
      important targets of forensic research. In this study, we examined fatty acid
      composition as a signature for the types of complex nutrients in the culturing
      medium. Bacillus cereus T-strain spores were grown in medium formulations
      supplemented with one of the following: peptone (meat protein), tryptone (casein
      protein), soy protein, and brain-heart infusion. Cellular biomass was profiled
      with fatty acid methyl ester (FAME) analysis. Results showed peptone cultures
      produced spores enriched in straight-chained lipids. Tryptone cultures produced
      spores enriched in branched-odd lipids when compared with peptone, soy, and brain
      heart formulations. The observed FAME variation was used to construct a set of
      discriminant functions that could help identify the nutrients in a culturing
      recipe for an unknown spore sample. Blinded classification tests were most
      successful for spores grown on media containing peptone and tryptone, showing 88%
      and 100% correct identification, respectively. 

PMID- 25854711
TI  - Editorial Comment to Prostate-specific antigen-based prostate cancer screening:
      Past and future.

PMID- 25854712
TI  - Human Vascular Wall Mesenchymal Stromal Cells Contribute to Abdominal Aortic
      Aneurysm Pathogenesis Through an Impaired Immunomodulatory Activity and Increased
      Levels of Matrix Metalloproteinase-9.
AB  - BACKGROUND: The main histopathological features of abdominal aortic aneurysm
      (AAA) are tissue proteolysis mediated by matrix metalloproteinases (MMPs) and
      inflammation. This study aimed at verifying the presence and contribution of
      mesenchymal stromal cells (MSCs) to aneurysmal tissue remodeling. METHODS AND
      RESULTS: MSCs were successfully isolated from the AAA wall of 12 male patients
      and were found to express mesenchymal and stemness markers. MMP-2/-9 are involved
      in AAA progression and their mRNA levels in AAA-MSCs resulted higher than healthy
      MSCs (cMSCs), especially MMP-9 (400-fold increased). Moreover, MMP-9 protein and
      activity were pronounced in AAA-MSCs. Immunomodulation was tested in AAA-MSCs
      after co-culture with activated peripheral blood mononuclear cells (PBMCs) and
      revealed a weak immunosuppressive action on PBMC proliferation (bromodeoxyuridine
      incorporation, flow cytometry assay), together with a reduced expression of anti
      inflammatory molecules (HLA-G, IL-10) by AAA-MSCs compared to cMSCs. MMP-9
      expression in AAA-MSCs was shown to be negatively modulated under the influence
      of cMSCs and exogenous IL-10. CONCLUSIONS: MSCs with stemness properties are
      niched in human AAA tissues and display a dysregulation of functional activities;
      that is, upregulation of MMP-9 and ineffective immunomodulatory capacity, which
      are crucial in the AAA progression; the possibility to modulate the increased MMP
      9 expression by healthy MSCs and IL-10 suggests that novel therapeutic strategies
      are possible for slowing down AAA progression.

PMID- 25854713
TI  - Visual Assessment of Relative Apical Sparing Pattern Is More Useful Than
      Quantitative Assessment for Diagnosing Cardiac Amyloidosis in Borderline or
      Mildly Increased Left Ventricular Wall Thickness.
AB  - BACKGROUND: Relative apical sparing pattern of longitudinal strain (RapSP-LS) was
      suggested in advanced cardiac amyloidosis (CA). It is unclear whether it is
      present in less advanced CA. METHODS AND RESULTS: Patients with presumptive
      diagnosis of CA and mean left ventricular wall thickness (LVWT) <=14 mm were
      recruited. Apart from RapSP-LS visually identified, relative apical longitudinal
      strain index (RapLSI) was defined as [average apical LS/(average basal LS+average
      mid-ventricle LS)]. Among 119 patients included, 47 were finally diagnosed with
      CA. RapLSI was higher in the CA group compared to other causes of increased mean
      LVWT (P<0.001), but with a significant range of overlap noted. In contrast, RapSP
      LS visually assessed was noted in most CA patients (31/47, 66.0%) except in those
      with preserved LV ejection fraction, normal LVWT, and mildly decreased global LS,
      suggesting least advanced CA. On multivariate analysis of the added diagnostic
      role of RapSP-LS or RapLSI on top of clinical, electrocardiographic, and
      conventional echocardiographic parameters, addition of RapLSI produced only
      borderline increase in area under the curve of the multivariate model (P=0.05),
      whereas addition of RapSP-LS significantly increased it (P<0.001). CONCLUSIONS:
      Visual identification of RapSP-LS is useful in terms of added diagnostic value
      compared with quantitative calculation of RapLSI. Its clinical application,
      however, should be used with caution in patients with less advanced CA.

PMID- 25854714
TI  - Estimated pulmonary artery systolic pressure and sickle cell disease: a meta
      analysis and systematic review.
AB  - Many studies report estimated pulmonary artery systolic pressure (ePASP) in
      patients with sickle cell disease (SCD) screened by echocardiography. To better
      understand the prevalence and outcomes of elevated ePASP in clinically stable SCD
      patients, we conducted a random-effects meta-analysis. A total of 45 studies,
      representing 15 countries and including 6109 individuals, met our inclusion
      criteria. In most (70%) studies, elevated ePASP was defined by a tricuspid
      regurgitant velocity of 2.5 m/s. The prevalence of elevated ePASP was 21% (17
      26%) in children and 30% (26-35%) in adults. After adjustment for sex, SCD
      genotype, haemoglobin, hydroxycarbamide (hydroxyurea) treatment, country and
      publication year, age remained associated with elevated ePASP, yielding a 12%
      (0.4-23%) higher adjusted prevalence in adults. Few studies reported 6-min walk
      tests or mortality outcomes, and estimates were highly heterogeneous. In random
      effects meta-analyses, patients with elevated ePASP walked an estimated 30.4 (6.9
      53.9) metres less than those without elevated ePASP and had an associated
      mortality hazard ratio of 4.9 (2.4-9.7).

PMID- 25854715
TI  - A case for summary care records.

PMID- 25854719
TI  - Mobile diagnostics kit delivers test results in the community.

PMID- 25854720
TI  - Commission set up to improve urgent care for older people.

PMID- 25854721
TI  - Parkinson's carries higher risk of dying after admission.

PMID- 25854723
TI  - Campaign launched to tackle problems in Scottish hospitals.

PMID- 25854724
TI  - Domestic violence project shortlisted for national award.

PMID- 25854725
TI  - Politicians set out their stalls on the emergency care issue.

PMID- 25854726
TI  - Initiative launched to support the mental health of blue-light staff.

PMID- 25854727
TI  - Young people need our support.

PMID- 25854731
TI  - Board's eye view---Speak your mind.

PMID- 25854735
TI  - Swallowed magnets.

PMID- 25854741
TI  - How summary care records can improve patient safety.
AB  - Summary care records (SCRs), which have been created for more than 53 million
      people in England, contain clinical information from patients' GP electronic
      records and can be accessed by authorised healthcare workers in other settings.
      The information is available for viewing at any time day or night, anywhere in
      England, as long as strict information governance processes that protect
      patients' confidentiality are followed. As this article explains, enabling SCR
      viewing in an organisation is straightforward and requires no major capital
      funding. Early findings indicate that access to information in SCRs increases
      patient safety, improves the quality and effectiveness of care, and can save
      healthcare staff and their organisations time and money.

PMID- 25854742
TI  - Analgesia for people with acute ankle sprain.
AB  - Around 302,000 people with soft-tissue ankle injuries present to UK emergency
      departments every year (Ferran and Maffulli 2006). These patients are generally
      treated conservatively with analgesia, ice, compression and elevation, and rest.
      There is some discussion in the literature about whether or not people with these
      injuries should be treated with non-steroidal anti-inflammatory drugs (NSAIDs),
      with some authors claiming that the inflammatory response following injury is
      part of the healing process and should not be halted. This article examines the
      literature on the efficacy of administering NSAIDs as the first-line drug
      management for ankle sprain. It also considers cost of treatment, prescribing
      practice and contraindications of NSAIDs.

PMID- 25854743
TI  - Cardiovascular examination in emergency departments.
AB  - History taking and physical examination of patients who present with cardiac pain
      are not generally regarded as part of an emergency nurse's role in the UK.
      However, a good knowledge of the anatomy of the heart and cardiac disease, and
      the ability to undertake effective cardiovascular examination, could enable
      nurses to highlight adverse findings earlier in a patient's journey and improve
      patient outcomes. This article reviews the anatomy of the heart and
      cardiovascular disease, and describes how to pick out the subjective and
      objective information from patient histories and cardiac examination to make
      differential diagnoses. 

PMID- 25854744
TI  - Mesenchymal Stem Cells Facilitate In Vitro Development of Human Preantral
      Follicle.
AB  - Biological folliculogenesis is a lengthy and complicated process, and follicle
      growth microenvironment is poorly understood. Mesenchymal stem cells (MSCs) have
      been shown to establish a supportive microenvironment for wound repair,
      autoimmune diseases amelioration, and tumor development. Therefore, this study is
      aimed to investigate whether MSCs could help to reconstruct a microenvironment to
      facilitate the in vitro follicle development. Here we show human MSCs
      significantly promote the survival rates, increase the growth velocity, and
      improve the viability of preantral follicles in a dose-dependent manner. Further
      analyses reveal that growth differentiation factor 9 and bone morphogenetic
      protein 15 in oocytes and inhibin betaA and transforming growth factor beta1 in
      granulose cells within the follicles cocultured with MSCs express notably higher
      than those in the follicles cultured without MSCs. In summary, our findings
      demonstrate a previously unrecognized function of MSCs in promoting preantral
      follicle development and provide a useful strategy to optimize fertility
      preservation and restoration by facilitating in vitro follicle growth. 

PMID- 25854745
TI  - Failure of temporal selectivity: Electrophysiological evidence for (mis)selection
      of distractors during the attentional blink.
AB  - The attentional blink (AB) refers to the impairment in accurate report of a
      second target (T2) when presented shortly after a first target (T1) in a rapid
      serial visual presentation of distractors. The goal of the present study was to
      determine whether the AB is caused by a failure in early selection processes,
      which leads to the selection and consolidation of the wrong item in working
      memory, by measuring the frequency-related P3 to T2 and to T2 + 1. During the AB,
      an attenuation of the P3 to T2 was observed, as well as an increase in the
      amplitude of the P3 to T2 + 1. Whereas the P3 to T2 was observed only when T2 was
      correctly reported, the P3 to T2 + 1 was observed only in trials where T2 was
      incorrectly reported, and its amplitude was correlated to individual differences
      in misselection rate. These results support the claim that failure of temporal
      selection underlies the AB.

PMID- 25854746
TI  - [Sport and the Heart - not a simple connection].

PMID- 25854747
TI  - Symptom report and treatment experience of hypogonadal men with and without type
      2 diabetes in a United States health plan.
AB  - BACKGROUND: Although hypogonadism (HG) is interrelated with type 2 diabetes
      mellitus (T2DM), there is little information about men's experiences with HG,
      T2DM, and testosterone replacement therapy (TRT). We examined symptoms and TRT
      use among men with HG, with and without T2DM, who received care within a single
      United States health plan. METHODS: Men aged >= 18 years with HG, with and
      without T2DM, were identified from the 2008 to 2010 Reliant Medical Group
      electronic medical record database. Surveys responses compared by T2DM status
      using chi-square or Wilcoxon rank sum tests. RESULTS: A total of 93 men were
      included (19 with HG and T2DM, 74 with HG only). Men with both HG and T2DM were
      more frequently treated for their HG by an endocrinologist (52.6%), compared with
      men with HG only (28.4%, p = 0.058). Erectile dysfunction (ED) was the primary
      reason for seeking care among all surveyed men, although men with HG and T2DM
      reported experiencing ED more often (94.7%) than men with HG only (46.0%, p <
      0.0001). Additional reasons for seeking care were similar between cohorts and
      included loss of energy and decreased sex drive. Most men (88.2%) reported using
      TRT, primarily as injection or gel formulations. Discontinuation of TRT was
      reported slightly more frequently by men with HG and T2DM (68.4%), compared with
      men with HG only (55.4%, p > 0.05). CONCLUSIONS: This study provides information
      about symptoms and TRT utilisation among HG men with and without T2DM. Men with
      HG only were less likely than those with both HG and T2DM to report that they
      were currently experiencing key symptoms compared with when they were first
      diagnosed, regardless of TRT utilisation, and were less likely to report ED as a
      current symptom.

PMID- 25854748
TI  - Evaluation of resting state gamma power as a response marker in schizophrenia.
AB  - AIMS: An abnormal activity in the electroencephalography (EEG) gamma band (>30
      Hz) has been demonstrated in schizophrenia and this has been suggested to be
      reflecting a deficit in the development and maturation of the basic cognitive
      functions of attention, working memory and sensory processing. Hypothesizing
      gamma oscillatory activity as a potential EEG biomarker to antipsychotic response
      in schizophrenia, the present study aimed at measuring baseline spontaneous gamma
      activity in schizophrenia patients, and evaluating its response to antipsychotic
      treatment over 8 weeks. METHODS: Fifteen drug-free/naive patients were recruited,
      compared at baseline with 15 age-, sex- and education-matched healthy controls,
      and were followed up for 8 weeks' treatment on antipsychotics. Resting state EEG
      waves were recorded using high (192-channel) resolution EEG at admission, 4 weeks
      and 8 weeks. Spectral power was calculated using fast Fourier transformation,
      Hanning window. The power was averaged region-wise over nine regions in three
      frequency ranges (30-50 Hz, 50-70 Hz, 70-100 Hz). RESULTS: Patients and controls
      differed significantly at intake in terms of left temporal and parietal high (70
      100 Hz) gamma power. Consequently, no significant differences were seen over the
      course of antipsychotic treatment on gamma spectral power in any of the regions.
      CONCLUSIONS: Lack of significant effect of treatment on gamma power suggests that
      these gamma oscillations may be trait markers in schizophrenia.

PMID- 25854749
TI  - Assessment of airborne heavy metal pollution in soil and lichen in the Meric
      Ergene Basin, Turkey.
AB  - In the present study, accumulations of airborne heavy metals in lichen and soil
      samples were determined on the basis of pollutant source groups by conducting
      Zinc (Zn), Lead (Pb), Iron (Fe), Copper (Cu), Chromium (Cr), Cadmium (Cd),
      Arsenic (As), Cobalt (Co) and Manganese (Mn) analyses on a total of 48 samples
      collected in the periods of May 2014 and August 2014 from 12 sampling points in a
      heavily industrialized area, a mixed industrial and residential area, an
      agricultural area and a background area in the Meric-Ergene Basin, and pH and
      total organic carbon determination was carried out on soil samples. With the
      obtained data, heavy metal levels were statistically assessed in detail by being
      associated with each other and with their probable sources; the accumulations
      found in soil and lichen samples were compared and spatial variances were set
      forth. Based on the results, it was observed that heavy metal pollution is at
      high levels particularly in industrialized areas, and that the differences
      between the cleanest and most polluted levels determined from soil samples for
      As, Cr, Cd and Pb reach 10 folds. The highest levels of all heavy metals were
      determined in both the soil and lichen samples collected from the areas in the
      south-east part of the region, where industrial activities and particularly
      leather and chemical industries are concentrated. With the comparison of the
      indication properties of soil and lichen, it was determined that significant and
      comparable results can be observed in both matrices. 

PMID- 25854750
TI  - New approach for a reliable in vitro sun protection factor method Part I:
      Principle and mathematical aspects.
AB  - OBJECTIVE: Development of an international harmonized in vitro method for sun
      protection factor (SPF) assessment is currently in progress because of the lack
      of both reproducibility and accuracy in the current methodology. The aim of this
      article was to focus on the principle and mathematical aspects (Part I) of a new
      approach for a reproducible and correlated in vitro test method to obtain results
      similar to the in vivo SPF for labelling purposes. METHODS: The currently used in
      vitro test is based on the spectroradiometric measurement of the residual
      ultraviolet (UV) transmitted through a thin layer of sunscreen spread on a
      substrate. To reach the goals of reproducibility and accuracy, the specifications
      of the key parameters and different steps of the procedure are clearly described
      in this study. RESULTS: Once reproducibility is obtained with an ad hoc
      procedure, the accuracy of the SPF values for a large number of products can be
      demonstrated with the prerequisite of a single UV irradiation dose and a
      multisubstrate solution. Using a total of 27 samples, the mean coefficient of
      variation was found to be <10% and the coefficient of correlation with the SPF
      clinical value reached approximately 0.81. CONCLUSION: The first part of the
      article revealed a relevant tool for the in vitro SPF assessment that can be
      closely correlated to the in vivo SPF for labelling purposes. The second part
      study will focus on the practical aspects and implementation (Part II) achieved
      using the present method, will validate the robustness of the models and
      demonstrate the need to have different product categories to reach a reliable in
      vitro SPF method adaptable for all products available in the market.

PMID- 25854751
TI  - Solution phase synthesis and intense pulsed light sintering and reduction of a
      copper oxide ink with an encapsulating nickel oxide barrier.
AB  - Copper oxide nanoparticle inks sintered and reduced by intense pulsed light (IPL)
      are an inexpensive means to produce conductive patterns on a number of
      substrates. However, the oxidation and diffusion characteristics of copper are
      issues that must be resolved before it can be considered as a viable solution.
      Nickel can provide a degree of oxidation protection and act as a barrier for the
      diffusion of copper. In the present study we have for the first time synthesized
      copper oxide with an encapsulating nickel oxide nanostructure using a solution
      phase synthesis process in the presence of a surfactant at room temperature. The
      room temperature process enables us to easily prevent the formation of alloys at
      the copper-nickel interface. The synthesis results in a simple technique (easily
      commercializable, tested at a 10 g scale) with highly controllable layer
      thicknesses on a 20 nm copper oxide nanoparticle. These Cu(2)O@NiO dispersions
      were then directly deposited onto substrates and sintered/reduced using an IPL
      source. The sintering technique produces a highly conductive film with very short
      processing times. Films have been deposited onto silicon, and the copper-nickel
      structure has shown a lower copper diffusion. The nanostructures and resulting
      films were characterized using electron and x-ray spectroscopy, and the films'
      resistivity was measured.

PMID- 25854752
TI  - Synthesis, crystal structures and spectroscopic properties of triazine-based
      hydrazone derivatives; a comparative experimental-theoretical study.
AB  - We report here a comparative theoretical and experimental study of four triazine
      based hydrazone derivatives. The hydrazones are synthesized by a three step
      process from commercially available benzil and thiosemicarbazide. The structures
      of all compounds were determined by using the UV-Vis., FT-IR, NMR (1H and 13C)
      spectroscopic techniques and finally confirmed unequivocally by single crystal X
      ray diffraction analysis. Experimental geometric parameters and spectroscopic
      properties of the triazine based hydrazones are compared with those obtained from
      density functional theory (DFT) studies. The model developed here comprises of
      geometry optimization at B3LYP/6-31G (d, p) level of DFT. Optimized geometric
      parameters of all four compounds showed excellent correlations with the results
      obtained from X-ray diffraction studies. The vibrational spectra show nice
      correlations with the experimental IR spectra. Moreover, the simulated absorption
      spectra also agree well with experimental results (within 10-20 nm). The
      molecular electrostatic potential (MEP) mapped over the entire stabilized
      geometries of the compounds indicated their chemical reactivates. Furthermore,
      frontier molecular orbital (electronic properties) and first hyperpolarizability
      (nonlinear optical response) were also computed at the B3LYP/6-31G (d, p) level
      of theory. 

PMID- 25854753
TI  - The encapsulation of anthocyanins from berry-type fruits. Trends in foods.
AB  - During the last decade, many berry-type fruits have been recognised as good
      sources of anthocyanins. Nevertheless, the use of anthocyanins in the development
      of food colourants and healthy and/or functional ingredients has been limited
      because of their low stability under given environmental conditions and
      interaction with other compounds in the food matrix. This review compiles
      information about the encapsulation of anthocyanins from twelve different berry
      type fruit species as a technology for improving the stability and/or
      bioavailability of anthocyanins. Encapsulation by spray drying has been the
      primary method used to encapsulate anthocyanins, and some studies attempt to keep
      anthocyanin microparticles stable during storage. Nevertheless, more studies are
      needed to determine the stability of anthocyanin microparticles in food matrices
      over the product shelf life in the development of food colourants. Studies about
      encapsulated anthocyanins in simulated gastrointestinal models have primarily
      been conducted on the release of anthocyanins from microparticles to evaluate
      their bioavailability. However, adding anthocyanin microparticles to a food
      vehicle must guarantee the health properties attributed to the specific
      anthocyanins present in berry-type fruits. 

PMID- 25854754
TI  - Formulations, hemolytic and pharmacokinetic studies on saikosaponin a and
      saikosaponin d compound liposomes.
AB  - The aim of this study was to develop and optimise a saikosaponin a and
      saikosaponin d compound liposome (SSa-SSd-Lip) formulation with reduced hemolysis
      and enhanced bioavailability. A screening experiment was done with Plackett
      Burman design, and response surface methodology of five factors (EPC/SSa-SSd
      ratio, EPC/Chol ratio, water temperature, pH of PBS, and ultrasound time) was
      employed to optimise the mean diameter, entrapment efficiency of SSa and SSd, and
      the reduction of hemolysis for SSa-SSd-Lip. Under the optimal process conditions
      (EPC/SSa-SSd ratio, EPC/Chol ratio, water temperature and pH of PBS were 26.71,
      4, 50  degrees C and 7.4, respectively), the mean diameter, the entrapment
      efficiency of SSa, the entrapment efficiency of SSd and the hemolysis were 203
      nm, 79.87%, 86.19%, 25.16% (SSa/SSd 12.5 mg/mL), respectively. The
      pharmacokinetic studies showed that the SSa-SSd-Lip had increased circulation
      time, decreased Cl, and increased AUC, MRT and T1/2beta (p < 0.05) for both SSa
      and SSd after intravenous administration in comparison with solution. 

PMID- 25854755
TI  - Enhanced materials from nature: nanocellulose from citrus waste.
AB  - Nanocellulose is a relatively inexpensive, highly versatile bio-based renewable
      material with advantageous properties, including biodegradability and
      nontoxicity. Numerous potential applications of nanocellulose, such as its use
      for the preparation of high-performance composites, have attracted much attention
      from industry. Owing to the low energy consumption and the addition of
      significant value, nanocellulose extraction from agricultural waste is one of the
      best alternatives for waste treatment. Different techniques for the isolation and
      purification of nanocellulose have been reported, and combining these techniques
      influences the morphology of the resultant fibers. Herein, some of the extraction
      routes for obtaining nanocellulose from citrus waste are addressed. The
      morphology of nanocellulose was determined by Scanning Electron Microscopy (SEM)
      and Field Emission Scanning Electron Microscopy (FESEM), while cellulose
      crystallinity indexes (CI) from lyophilized samples were determined using solid
      state Nuclear Magnetic Resonance (NMR) and X-Ray Diffraction (XRD) measurements.
      The resultant nanofibers had 55% crystallinity, an average diameter of 10 nm and
      a length of 458 nm. 

PMID- 25854756
TI  - Carboxylated acyclonucleosides: synthesis and RNase A inhibition.
AB  - Strategically designed carboxylated acyclonucleosides have been probed as a new
      class of RNase A inhibitors. Several experimental and theoretical studies have
      been performed to compile relevant qualitative and quantitative information
      regarding the nature and extent of inhibition. The inhibition constant (Ki)
      values were determined using a UV-based kinetics experiment. The changes in the
      secondary structure of the enzyme upon binding with the inhibitors were obtained
      from circular dichroism studies. The binding constants for enzyme-inhibitor
      interactions were determined with the help of fluorescence spectroscopy. Docking
      studies were performed to reveal the possible binding sites of the inhibitors
      within the enzyme. The cytosine analogues were found to possess better inhibitory
      properties in comparison to the corresponding uracil derivatives. An increment in
      the number of carboxylic acid groups (-COOH) in the inhibitor backbone was found
      to result in better inhibition. 

PMID- 25854757
TI  - Probing the relationship between anti-Pneumocystis carinii activity and DNA
      binding of bisamidines by molecular dynamics simulations.
AB  - The anti-Pneumocystis carinii activity of 13 synthetic pentamidine analogs was
      analyzed. The experimental differences in melting points of DNA dodecamer 5'
      (CGCGAATTCGCG)2-3' complexes (DeltaTm), and in the biological activity measured
      using ATP bioluminescence assay (IC50) together with the theoretical free energy
      of DNA-ligand binding estimated by the proposed computational protocol, showed
      that the experimental activity of the tested pentamidines appeared to be due to
      the binding to the DNA minor groove with extended AT sequences. The effect of
      heteroatoms in the aliphatic linker, and the sulfonamide or methoxy substituents
      on the compound inducing changes in the interactions with the DNA minor groove
      was examined and was correlated with biological activity. In computational
      analysis, the explicit solvent approximation with the discrete water molecules
      was taken into account, and the role of water molecules in the DNA-ligand
      complexes was defined. 

PMID- 25854758
TI  - A new 9,10-dihydrophenanthrene and cell proliferative 3,4-delta
      dehydrotocopherols from Stemona tuberosa.
AB  - A new compound, 9,10-dihydro-5-methoxy-8-methyl-2,7-phenanthrenediol (1), was
      isolated from the roots of Stemona tuberosa Lour. (Stemonaceae) together with two
      new optically active compounds, (2S,4'R,8'R)-3,4-delta-dehydrotocopherol (2) and
      (2R,4'R,8'R)-3,4-delta-dehydrotocopherol (3). The structures of compounds 1-3
      were determined on the basis of spectroscopic data analysis. Compounds 2 and 3
      were each purified from a stereoisomeric mixture of 2 and 3 by preparative HPLC
      using a chiral column for the first time. The absolute configurations at C-2 of 2
      and 3 were determined by Circular Dichroism (CD) experiments. As a part of the
      research to find natural wound healing agents, all isolates and the mixture of 2
      and 3 were evaluated for their cell proliferative effects using a mouse
      fibroblast NIH3T3 and a HeLa human cervical cancer cell line. As a result, 1, 2,
      3, or the mixture of 2 and 3 showed 41.6%, 78.4%, 118.6%, 38.2% increases of cell
      proliferation in the mouse fibroblast NIH3T3 respectively, compared to 28.4%
      increase of delta-tocopherol. Moreover, none of them induced cancer cell
      proliferation. Therefore, 3,4-delta-dehydrotocopherols, especially pure isomers 2
      and 3 can be suggested as potential wound healing agents. 

PMID- 25854759
TI  - Bayesian nonlinear model selection for gene regulatory networks.
AB  - Gene regulatory networks represent the regulatory relationships between genes and
      their products and are important for exploring and defining the underlying
      biological processes of cellular systems. We develop a novel framework to recover
      the structure of nonlinear gene regulatory networks using semiparametric spline
      based directed acyclic graphical models. Our use of splines allows the model to
      have both flexibility in capturing nonlinear dependencies as well as control of
      overfitting via shrinkage, using mixed model representations of penalized
      splines. We propose a novel discrete mixture prior on the smoothing parameter of
      the splines that allows for simultaneous selection of both linear and nonlinear
      functional relationships as well as inducing sparsity in the edge selection.
      Using simulation studies, we demonstrate the superior performance of our methods
      in comparison with several existing approaches in terms of network reconstruction
      and functional selection. We apply our methods to a gene expression dataset in
      glioblastoma multiforme, which reveals several interesting and biologically
      relevant nonlinear relationships. 

PMID- 25854760
TI  - Effects of performing electrocardio-graphy in the community on overall coronary
      artery ischemia time in patients with acute myocardial infarction.

PMID- 25854762
TI  - Radical scavenging and anti-inflammatory effects of the halophyte Spergularia
      marina Griseb.
AB  - As a part of ongoing research to develop antioxidant and anti-inflammatory
      nutraceuticals, an ethanolic extract of Spergularia marina Griseb. was tested for
      its ability to scavenge radicals and suppress inflammation. The extract was able
      to scavenge 1,1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl, and superoxide
      radicals, respectively, in cell-free environments as well as intracellular
      radicals in H2O2-stimulated mouse macrophages. Inflammation in mouse macrophages
      induced by lipopolysaccharides was suppressed by S. marina according to the
      measurement of nitric oxide generation and expression of inflammatory cytokines,
      i.e. tumour necrosis factor-alpha (TNFalpha), interleukin (IL)-1beta, and IL-6.
      The anti-inflammatory effect of S. marina was substantiated by the finding that
      the expression of the inflammatory modulators, inducible nitric oxide synthase
      (iNOS) and cyclooxygenase-2 (COX-2), was significantly decreased. The chemical
      composition of S. marina was evaluated by FT-IR analysis of the extract
      indicating the presence of polyphenols and flavonoids. In conclusion, S. marina
      is suggested as a novel source for antioxidant and anti-inflammatory agents. 

PMID- 25854763
TI  - Mechanisms underlying the relaxant effect of Galetin 3,6- dimethyl ether, from
      Piptadenia stipulacea (Benth.) Ducke, on guinea-pig trachea.
AB  - Galetin 3,6-dimethyl ether (FGAL), a flavonoid from the aerial parts of
      Piptadenia stipulacea (Benth.) Ducke, was found to exert a relaxant effect on
      carbachol (CCh)-pre-contracted guinea-pig trachea. Based on cumulative
      concentration-response curves to CCh, FGAL antagonized muscarinic receptors
      pseudo-irreversibly and noncompetitively, since it inhibited and shifted these
      curves towards higher concentrations in a nonparallel manner. In addition, FGAL
      was more potent in relaxing contractions induced by 18 mM as compared to 60 mM
      KCl (pD2 = 5:50 +/-0:36 and 4.80 +/-0.07, respectively), indicating the
      participation of K+ channels. In the presence of 10 mM tetraethylammonium (TEA+)
      chloride, a nonselective K+ channel blocker, the relaxant potency of FGAL was
      reduced (from pD2 = 5:12 +/-0:07 to 4.87 +/-0.02). Among several selective
      blockers of K+ channel subtypes, only apamin, an SKCa (small-conductance Ca2+
      activated K+ channels) blocker, attenuated the relaxant potency of FGAL (pD2 =
      4:85+/-0:06), suggesting SKCa activation. FGAL was equipotent in relaxing trachea
      contracted by 60 mM KCl (pD2 =4:80 +/-0:07) or 10-6 M CCh (pD2 = 5:02 +/-0:07),
      suggesting CaV (voltage-gated calcium channel), but not ROCs (receptor-operated
      calcium channels) participation. Furthermore, aminophylline-induced relaxation
      (pD2 = 4:12 +/-0:06) was potentiated around 4-fold (pD2 = 4:80 +/-0:44) in the
      presence of FGAL. Moreover, forskolininduced relaxation (pD2 = 6:51 +/-0:06) was
      potentiated around 2.5-fold (pD2 = 6:90 +/-0:05) by FGAL. Conversely, sodium
      nitroprusside-induced relaxation was unaffected, indicating that the AC/cAMP/PKA
      pathway, but not the NO pathway, may be modulated by the flavonoid. These results
      suggest that, in guinea-pig trachea, FGAL induces relaxation by pseudo
      irreversible noncompetitive antagonism on muscarinic receptors, modulation of K+
      and Ca2+ channels, as well as activation of the AC/cAMP/PKA pathway. 

PMID- 25854764
TI  - Mechanistic studies of antiproliferative effects of Salvia triloba and Salvia
      dominica (Lamiaceae) on breast cancer cell lines (MCF7 and T47D).
AB  - Ethanol extracts obtained from two Salvia species, S. triloba and S. dominica,
      collected from the flora of Jordan, were evaluated for their antiproliferative
      activity against MCF7 and T47D breast cancer cell lines by the sulforhodamine B
      assay. The ethanol extracts were biologically active with IC50 values of (29.89
      +/-0.92) and (38.91 +/-2.44) MUg/mL for S. triloba against MCF7 and T47D cells,
      respectively, and (5.83 +/-0.51) and (12.83 +/-0.64) MUg/mL for S. dominica
      against MCF7 and T47D cells, respectively. Flow cytometry analysis and the
      annexinV-propidium iodide (PI) assay revealed apoptosismediated, and to a lesser
      extent necrosis-induced, cell death by the S. triloba and S. dominica ethanolic
      extracts in T47D cells. The mechanism of apoptosis was further investigated by
      determining the levels of p53, p21/WAF1, FasL (Fas ligand), and sFas (Fas/APO-1).
      The extract from S. triloba induced a more pronounced enrichment in cytoplasmic
      mono- and oligonucleosomes than that from S. dominica (p < 0:05) in T47D cells.
      In response to the extract from S. dominica, but not from S. triloba, the
      proapoptotic efficacy was specifically regulated by p21. Extracts from both
      Salvia spp. did not enhance p53 levels, and apoptosis induced by them was not
      caspase-8- or sFas/FasL-dependent. Thus, our findings indicate that S. triloba
      and S. dominica ethanolic extracts may be useful in breast cancer
      management/treatment via proapoptotic cytotoxic mechanisms. 

PMID- 25854761
TI  - Whole-exome SNP array identifies 15 new susceptibility loci for psoriasis.
AB  - Genome-wide association studies (GWASs) have reproducibly associated ~40
      susceptibility loci with psoriasis. However, the missing heritability is evident
      and the contributions of coding variants have not yet been systematically
      evaluated. Here, we present a large-scale whole-exome array analysis for
      psoriasis consisting of 42,760 individuals. We discover 16 SNPs within 15 new
      genes/loci associated with psoriasis, including C1orf141, ZNF683, TMC6, AIM2,
      IL1RL1, CASR, SON, ZFYVE16, MTHFR, CCDC129, ZNF143, AP5B1, SYNE2, IFNGR2 and
      3q26.2-q27 (P<5.00 * 10(-08)). In addition, we also replicate four known
      susceptibility loci TNIP1, NFKBIA, IL12B and LCE3D-LCE3E. These susceptibility
      variants identified in the current study collectively account for 1.9% of the
      psoriasis heritability. The variant within AIM2 is predicted to impact protein
      structure. Our findings increase the number of genetic risk factors for psoriasis
      and highlight new and plausible biological pathways in psoriasis.

PMID- 25854765
TI  - Regulation of growth and photosynthetic parameters by salicylic acid and calcium
      in Brassica juncea under cadmium stress.
AB  - Cadmium, a non-essential and toxic metal, negatively affects plant growth and
      productivity, and alters the plant's physiological processes necessary for its
      survival. The present study was designed to explore the individual and combined
      effects of calcium and salicylic acid (SA) on the morphology and physiology of
      Brassica juncea L. cv. Varuna under cadmium stress. The application of calcium (2
      mM) through the soil and/or SA (10-5 M) as foliar spray enhanced the growth,
      photosynthetic parameters, and proline content determined after 45 days of
      treatment. The application of cadmium (6 mg kg-1) through the soil was toxic and
      decreased both growth and the photosynthetic parameters. The application of
      calcium and SA in combination was most effective in alleviating the harmful
      effects of cadmium on growth and photosynthesis. Calcium and SA clearly induced
      plant protection mechanisms by enhancing proline and chlorophyll accumulation in
      the leaves. 

PMID- 25854766
TI  - Cardioprotective effect of saffron extracts against acute doxorubicin toxicity in
      isolated rabbit hearts submitted to ischemia-reperfusion injury.
AB  - Doxorubicin (DOX) is an anthracycline antibiotic routinely used as a
      chemotherapeutic agent for the treatment of solid tumours. However, DOX possesses
      an acute and cumulative cardiotoxicity due to free radical production. The
      present study was designed to investigate the possible protective effects of
      saffron (Crocus sativus) extracts against DOX-induced acute cardiotoxicity in
      isolated rabbit hearts submitted to 30 min global ischemia followed by 40 min
      reperfusion. DOX was delivered during reperfusion, without or with saffron given
      5 min before ischemia or at reperfusion. Cardiodynamic, biochemical, and
      histopathological parameters were determined. In addition, to determine the
      expression of the AKT/mTOR/4EBP1 pathway, the levels of p38 MAPK and cardiac
      troponin T in heart homogenates were visualized by Western blotting. DOX
      administration during 40 min of reperfusion increased ischemic tissue damage, but
      did not act synergistically. Administration of saffron extracts during the first
      minutes of reperfusion significantly reduced oxidative myocardial damage, but was
      less effective when given before ischemia. Subsequent Western blot analysis
      revealed that saffron administration preserved cardiac troponin T proteins,
      inhibited the p38 MAPK pathway, and activated the AKT/mTOR/4EBP1 pathway in
      reperfusion- and DOX-treated rabbit hearts. In conclusion, saffron extracts,
      acting through antioxidant and antiapoptotic mechanisms, exhibited a protective
      effect against DOX-induced cardiotoxicity under ischemic condition. 

PMID- 25854767
TI  - Ratjadone C-mediated nuclear accumulation of HDAC4: implications on Runx2-induced
      osteoblast differentiation of C3H10T1/2 mesenchymal stem cells.
AB  - Histone deacetylases (HDACs) are a group of enzymes that deacetylate epsilon-N
      acetyl lysine residues of histone and non-histone proteins and play an important
      role in gene regulation. HDAC4, a class-IIa HDAC, has been reported to shuttle
      between nucleus and cytoplasm in response to various cellular stimuli. The nucleo
      cytoplasmic shuttling of HDAC4 is critical, and an anomalous nuclear localization
      might affect the cellular differentiation program. While the subcellular
      localization of HDAC4 has been reported to be vital for myoblast differentiation
      and chondrocyte hypertrophy, nuclear accumulation of HDAC4 during Runx2-induced
      osteoblast differentiation of stem cells has not been characterized. Ratjadone C
      is a natural compound that inhibits the nuclear export of proteins. Here, we show
      that Runx2 is a more potent transcription factor than Osterix in inducing
      osteoblast differentiation. Under the influence of ratjadone C, HDAC4 is retained
      in the nucleus and co-localizes with Runx2. However, forced nuclear accumulation
      of HDAC4 by ratjadone C or overexpression of the nuclear resident form of HDAC4
      does not inhibit osteoblast differentiation, suggesting that the Runx2- induced
      osteogenic program of C3H10T1/2 cells is not affected by HDAC4. Even though
      phosphorylation of HDAC4 affects its compartmentalization and the stemness of
      progenitor cells, we found that total HDAC4 and phosphorylated HDAC4 remain
      cytoplasmic under both osteogenic and nonosteogenic conditions. Collectively,
      this work demonstrates that, regardless of the nucleo-cytoplasmic presence of
      HDAC4, the Runx2-induced osteoblast differentiation program of C3H10T1/2 cells
      remains unaffected. Additionally, the ratjadone C-mediated nuclear retention
      assay can potentially be used as a screening tool to identify novel regulatory
      mechanisms of HDAC4 and its functional partners in various pathophysiological
      conditions. 

PMID- 25854768
TI  - Expression and characterization of two beta-galactosidases from Klebsiella
      pneumoniae 285 in Escherichia coli and their application in the enzymatic
      synthesis of lactulose and 1-lactulose.
AB  - The two genes lacZ1 and lacZ2 from Klebsiella pneumoniae 285, encoding beta
      galactosidase isoenzymes II and III (KpBGase-II and -III), were each cloned
      downstream of a T7 promoter for expression in Escherichia coli BL21(DE3), and the
      resulting recombinant enzymes were characterized in detail. The optimum
      temperature and pH value of KpBGase-II were 40  degrees C and 7.5, and those of
      KpBGase-III were 50  degrees C and 8.0, respectively. KpBGase-III was more stable
      than KpBGase-II at higher temperature (>60 degrees C). Both beta-galactosidases
      were more active towards o-nitrophenyl-beta- D-galactopyranoside as compared to
      lactose. The enzymatic synthesis of lactulose and 1-lactulose catalyzed by
      KpBGase-II and KpBGase-III was investigated. Using 400 g/L lactose and 200 g/L
      fructose as substrates, the resulting lactulose and 1-lactulose yields with
      KpBGase-II were 6.2 and 42.3 g/L, while those with KpBGase-III were 5.1 and 23.8
      g/L, respectively. KpBGase-II has a potential for the production of 1-lactulose
      from lactose and fructose. Like other beta-galactosidases, the two isozymes
      catalyze the transgalactosylation in the presence of fructose establishing the
      beta-(1->1) linkage. 

PMID- 25854769
TI  - Central analgesic activity of the aqueous and ethanolic extracts of the leaves of
      Albizia lebbeck: role of the GABAergic and serotonergic pathways.
AB  - Albizia lebbeck Benth. is extensively used in Indian traditional medicine for
      treating several painful and inflammatory disorders. The possible central
      analgesic activity and the underlying mechanism of action of the aqueous (AE) and
      ethanolic extracts (EE) of the leaves of A. lebbeck were investigated in Wistar
      rats using Eddy's hot plate and the tail flick tests. In order to investigate the
      underlying mechanism of action, rats were pretreated with naloxone, bicuculline
      or methysergide and then were administered a per os (p.o.) dose of AE or EE. AE
      and EE caused a significant (p<0.05) elevation in the mean basal reaction time in
      the hot plate method and an increase in the latency time in the tail flick
      method. In rats pretreated with bicuculline and methysergide, a significant
      (p<0.05) reduction in the analgesic activity was observed in comparison to AE and
      EE. Thus, AE and EE exhibited significant central analgesic activity and act
      possibly via the GABAergic and serotonergic pathways. The flavonoids and saponins
      found in the leaves could be responsible for the observed effect. 

PMID- 25854772
TI  - Exercise proteinuria and hematuria: current knowledge and future directions.
AB  - INTRODUCTION: Transient proteinuria and hematuria are apparently benign sequelae
      of intensive physical activity. However, there is a need to establish underlying
      causes and reasons for progression to chronic renal damage, as well as effects of
      training in healthy individuals and in those with microalbuminuria. EVIDENCE
      ACQUISITION: The Ovid/Health Star database was searched from 1994 to November
      2014. Terms for the kidneys (adverse effects, blood supply, epidemiology,
      injuries, pathology, physiology and secretion) and proteinuria (classification,
      complications, epidemiology, etiology, mortality, physiopathology, prevention and
      control) with terms related to physical activity (physical activity/motor
      activity, exercise/exercise therapy, fitness/physical fitness, physical
      education/physical education and training, and rehabilitation). EVIDENCE
      SYNTHESIS: Review of 519 abstracts yielded 194 relevant hits, supplemented by 70
      items from other sources. This material related to both healthy adults (125
      items) and renal disease (139 items). The prevalence (18-100%) and duration (1-6
      days) of exercise proteinuria varied widely, with risks affected by exercise
      intensity, posture, age, heat load, altitude and disease. Moderate training
      reduced exercise proteinuria in healthy individuals and in chronic renal disease.
      Factors contributing to exercise proteinuria may include vascular changes,
      hypoxia, lactate accumulation, oxidant stress, hormonal changes and sepsis.
      Exercise hematuria is frequent; some potential causes are similar to those for
      proteinuria, but foot-strike and bladder trauma are probably more important.
      Progression to permanent renal damage is rare. CONCLUSIONS: Exercise proteinuria
      and hematuria are generally transient. However, there remains a need to clarify
      causation and factors leading to permanent renal damage.

PMID- 25854771
TI  - The effect of different stretching techniques on ankle joint range of motion and
      dynamic postural stability after landing.
AB  - BACKGROUND: Stretching improves the flexibility of skeletal muscles, increases
      the range of motion (ROM) of joints. Stretching is important in prevention of
      sport-related injuries and influences muscle strength and performance. The
      effects of Static Stretching (SS) and Cyclic Stretching (CS) have been assessed
      by examining ROM, muscle power, vertical jump performance. However, the effects
      on postural control after CS compared with SS does not provide evidence for
      postural control after landing. The aim of this study was to examine the effects
      of stretching on the range of motion (ROM) of the ankle joint and dynamic
      postural stability upon landing on one leg. METHODS: Twenty healthy subjects
      participated in this study. Participants were randomly assigned to SS, CS, and
      control conditions. The ankle was stretched in each condition for two minutes in
      a standing position. In the assessment of dynamic postural stability, the
      participant jumped and landed on one leg onto a force platform and the Dynamic
      Postural Stability Index (DPSI) was measured. Stability indices including those
      for medial-lateral, anterior-posterior, and vertical stability were calculated.
      The data were compared among 3 conditions with repeated measures ANOVA and the
      correlation between ankle range of motion (ROM), DPSI and the maximum vertical
      ground reaction force (vGRF max) were calculated. RESULTS: The results indicated
      that the ROM was significantly greater after SS and CS compared with the control
      condition. A significant improvement in DPSI was observed after CS. CONCLUSIONS:
      We showed that 2 minutes of CS had a positive influence on dynamic postural
      stability after landing on a single leg. Furthermore, CS may improve balance by
      increasing postural stability.

PMID- 25854773
TI  - Adverse Effects of Genistein in a Mucopolysaccharidosis Type I Mouse Model.
AB  - Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disorder
      characterized by diminished degradation of the glycosaminoglycans heparan sulfate
      (HS) and dermatan sulfate (DS). Patients present with a variety of symptoms,
      including severe skeletal disease. Current therapeutic strategies have only
      limited effects on bone disease. The isoflavone genistein has been studied as a
      potential therapy for the mucopolysaccharidoses because of its putative ability
      to inhibit GAG synthesis and subsequent accumulation. Cell, animal, and clinical
      studies, however, showed variable outcomes. To determine the effects of genistein
      on MPS I-related bone disease, wild-type (WT) and MPS I mice were fed a genistein
      supplemented diet (corresponding to a dose of approximately 160 mg/kg/day) for 8
      weeks. HS and DS levels in bone and plasma remained unchanged after genistein
      supplementation, while liver HS levels were decreased in genistein-fed MPS I mice
      as compared to untreated MPS I mice. Unexpectedly, genistein-fed mice exhibited
      significantly decreased body length and femur length. In addition, 60% of
      genistein-fed MPS I mice developed a scrotal hernia and/or scrotal hydrocele,
      manifestations, which were absent in WT or untreated MPS I mice. In contrast to
      studies in MPS III mice, our study in MPS I mice demonstraes no beneficial but
      even potential adverse effects of genistein supplementation. Our results urge for
      a cautious approach on the use of genistein, at least in patients with MPS I. 

PMID- 25854774
TI  - Expanding the Clinical and Magnetic Resonance Spectrum of Leukoencephalopathy
      with Thalamus and Brainstem Involvement and High Lactate (LTBL) in a Patient
      Harboring a Novel EARS2 Mutation.
AB  - Leukoencephalopathy with thalamus and brainstem involvement and high lactate
      (LTBL) is a novel mitochondrial disease caused by mutations in EARS2, which
      encodes the mitochondrial glutamyl-tRNA synthetase (mtGluRS). A distinctive brain
      MRI pattern is the hallmark of the disease.A 6-year-old boy presented at 3 months
      with feeding difficulties and muscle hypotonia. Brain MRI, at 8 months, showed
      hyperintensity of the deep cerebral and cerebellar white matter, thalamus, basal
      ganglia, brainstem, and thin corpus callosum. From the second year of life
      onward, the child reported global clinical improvement, parallel to partial
      resolution of brain MRI pattern. However, the last neuroimaging assessment
      revealed novel lesions within the left caudate and pallidum nuclei. DNA genomic
      sequencing analysis identified a novel EARS2 mutation.This case expands the
      clinical and neuroradiological phenotype of LTBL presenting intermediate clinical
      manifestations between the severe and milder forms of the disease and previously
      unreported brain MRI features. 

PMID- 25854775
TI  - Modulation of the Nitrergic Pathway via Activation of PPAR-gamma Contributes to
      the Neuroprotective Effect of Pioglitazone Against Streptozotocin-Induced Memory
      Dysfunction.
AB  - Alzheimer's disease (AD) is a neurodegenerative disease characterized by impaired
      memory function and oxidative damage. NO is a major signaling molecule produced
      in the central nervous system to modulate neurological activity through
      modulating nitric oxide synthase. Recently, PPAR-gamma agonists have shown
      neuroprotective effects in neurodegenerative disorders. However, there have been
      only a few studies identifying mechanisms through which cognitive benefits may be
      exerted. The present study was designed to investigate the possible nitric oxide
      mechanism in the protective effect of pioglitazone against streptozotocin (STZ)
      induced memory dysfunction. Wistar rats were intracerebroventricularly (ICV)
      injected with STZ. Then rats were treated with pioglitazone, NO modulators [L
      arginine and nitro-L-arginine methyl ester (L-NAME)] for 21 days. Behavioral
      alterations were assessed in between the study period. Animals were sacrificed
      immediately after behavioral session, and mito-oxidative parameters, TNF-alpha,
      IL-6, and caspase-3 activity were measured. STZ-treated rats showed a memory
      deficit and significantly increased in mito-oxidative damage and inflammatory
      mediators and apoptosis in the hippocampus. Chronic treatment of pioglitazone
      significantly improved memory retention and attenuated mito-oxidative damage
      parameters, inflammatory markers, and apoptosis in STZ-treated rats. However, L
      arginine pretreatment with lower dose of pioglitazone has not produced any
      protective effect as compared to per se. Furthermore, pretreatment of L-NAME
      significantly potentiated its protective effect, which indicates the involvement
      of nitric oxide for activation of PPAR-gamma action. These results demonstrate
      that pioglitazone offers protection against STZ-induced memory dysfunction
      possibly due to its antioxidant, anti-inflammatory, and anti-apoptotic action
      mediating nitric oxide pathways and, therefore, could have a therapeutic
      potential in AD.

PMID- 25854776
TI  - Pirfenidone Attenuates Microglial Reactivity and Reduces Inducible Nitric Oxide
      Synthase mRNA Expression After Kainic Acid-Mediated Excitotoxicity in Pubescent
      Rat Hippocampus.
AB  - Excitotoxicity and neuroinflammation are strongly linked to the progressions of
      neurodegenerative diseases and acute injuries in the brain. Systematic
      administration of kainic acid (KA) in rodents causes severe limbic seizures,
      selective neuronal loss, and neuroinflammation in the hippocampus that are
      attributed to the excitotoxic process. Our previous report demonstrated the
      antioxidant and neuroprotective effects of pirfenidone (PFD) after the seizure
      onset induced by KA intraperitoneal injection. However, the aim of the present
      study is to analyze whether PFD has anti-inflammatory properties. Thus, pubescent
      male Wistar rats (30 days old) were exposed to 12 mg/Kg of KA, and the
      experimental group received KA and a single dose of 325 mg/Kg PFD in an
      orogastric tube at 90 min after KA exposure. The PFD treatment dramatically
      reduces the microglial activation observed by isolectin B4 staining and major
      histocompatibility complex II immunohistochemistry. We also determined that the
      messenger RNA of inducible nitric oxide synthase was downregulated by PFD
      treatment as measured 6 h after the KA injection. Our results indicate that the
      mechanism of neuroprotection after PFD treatment may include a decreased
      expression of the inducible nitric oxide synthase and reduced microglial
      activation. These findings suggest that PFD is a potentially useful strategy of
      the treatment for acute or chronic neurodegenerative diseases.

PMID- 25854777
TI  - Overexpression of 14-3-3zeta Increases Brain Levels of C/EBP Homologous Protein
      CHOP.
AB  - Recent studies demonstrated that overexpression of the molecular chaperone 14-3
      3zeta protects the brain against endoplasmic reticulum (ER) stress and prolonged
      seizures. The 14-3-3 targets responsible for improved neuronal survival after
      seizures remain unknown. Here we explored the mechanism, finding that protein
      levels of the ER-stress-associated transcription factor C/EBP homologous protein
      (CHOP) were significantly higher in 14-3-3zeta-overexpressing mice. Since
      previous studies by us demonstrated that loss of CHOP increased vulnerability to
      seizure damage, we explored whether elevated CHOP levels result from 14-3-3zeta
      overexpression and contribute to the protection. Pull-down experiments suggested
      that 14-3-3zeta could bind CHOP as well as sequester a CHOP-targeting microRNA.
      However, 14-3-3zeta overexpression remained protective against seizure-induced
      hippocampal injury in mice lacking CHOP. These studies reveal a novel function
      for 14-3-3zeta in regulating CHOP levels but show that this is not required for
      protection against seizure-induced neuronal death. 

PMID- 25854778
TI  - Neuroprotective Mechanisms of 9-Hydroxy Epinootkatol Against Glutamate-Induced
      Neuronal Apoptosis in Primary Neuron Culture.
AB  - Glutamate-induced neuronal apoptosis has been implicated in the pathogenesis of
      neurological disorders. 9-Hydroxy epinootkatol (9OHEN), a sesquiterpene compound
      with neuroprotective activity against glutamate-induced neuronal apoptosis, was
      isolated from Alpinia oxyphylla Miquel in our previous study. In this study, we
      investigated the neuroprotective mechanisms of 9OHEN against glutamate-induced
      neuronal apoptosis in primary cultured neurons. The results from this study
      demonstrated that 9OHEN protected cortical neurons from glutamate-induced
      neuronal apoptosis via inhibiting glutamate-induced activation of caspase-3,
      inhibiting glutamate-induced reactive oxygen species (ROS) production, inhibiting
      glutamate-induced nitric oxide (NO) production, and downregulating glutamate
      induced neuronal nitric oxide synthase (nNOS) expression. This study suggest that
      9OHEN might have therapeutic potential in treating glutamate-mediated
      neurological diseases. 

PMID- 25854779
TI  - Vitamin D Receptor Gene Polymorphism and the Risk of Multiple Sclerosis in South
      Eastern of Iran.
AB  - Multiple sclerosis is one of the most widespread demyelinating diseases of the
      central nervous system. Environmental and genetic factors are collaborating in
      triggering MS. The role of vitamin D receptor (VDR) gene and its polymorphisms
      are highlighted as susceptible components. The aim of the present study was to
      examine the association of single nucleotide polymorphism (SNP)-BsmI and FokI-in
      VDR gene and MS susceptibility in the South Eastern Iranian population.
      Therefore, 113 MS patients and 122 controls were recruited in the study.
      Restriction fragment length polymorphism was performed to detect the SNPs. There
      were no significant differences in the polymorphism of FokI (rs2228570) in VDR
      gene among patients and controls (P > 0.05), while a significant difference was
      observed in BsmI (rs1544410) polymorphism in healthy subjects and homozygous
      genotype-b/b- with MS (P = 0.025). Results showed a protective association of
      homozygous genotype-b/b- of BsmI with MS susceptibility in a population in South
      Eastern of Iran.

PMID- 25854780
TI  - Referral outcomes of individuals identified at high risk of cardiovascular
      disease by community health workers in Bangladesh, Guatemala, Mexico, and South
      Africa.
AB  - BACKGROUND: We have found that community health workers (CHWs) with appropriate
      training are able to accurately identify people at high cardiovascular disease
      (CVD) risk in the community who would benefit from the introduction of
      preventative management, in Bangladesh, Guatemala, Mexico, and South Africa. This
      paper examines the attendance pattern for those individuals who were so
      identified and referred to a health care facility for further assessment and
      management. DESIGN: Patient records from the health centres in each site were
      reviewed for data on diagnoses made and treatment commenced. Reasons for non
      attendance were sought from participants who had not attended after being
      referred. Qualitative data were collected from study coordinators regarding their
      experiences in obtaining the records and conducting the record reviews. The
      perspectives of CHWs and community members, who were screened, were also
      obtained. RESULTS: Thirty-seven percent (96/263) of those referred attended
      follow-up: 36 of 52 (69%) were urgent and 60 of 211 (28.4%) were non-urgent
      referrals. A diagnosis of hypertension (HTN) was made in 69% of urgent referrals
      and 37% of non-urgent referrals with treatment instituted in all cases. Reasons
      for non-attendance included limited self-perception of risk, associated costs,
      health system obstacles, and lack of trust in CHWs to conduct CVD risk
      assessments and to refer community members into the health system. CONCLUSIONS:
      The existing barriers to referral in the health care systems negatively impact
      the gains to be had through screening by training CHWs in the use of a simple
      risk assessment tool. The new diagnoses of HTN and commencement on treatment in
      those that attended referrals underscores the value of having persons at the
      highest risk identified in the community setting and referred to a clinic for
      further evaluation and treatment.

PMID- 25854781
TI  - Implementation of 5S management method for lean healthcare at a health center in
      Senegal: a qualitative study of staff perception.
AB  - BACKGROUND: 5S is a lean method for workplace organization; it is an abbreviation
      representing five Japanese words that can be translated as sort, set in order,
      shine, standardize, and sustain. The 5S management method has been recognized
      recently as a potential solution for improving the quality of government
      healthcare services in low- and middle-income countries. OBJECTIVE: To assess how
      the 5S management method creates changes in the workplace and in the process and
      outcomes of healthcare services, and how it can be applicable in a resource-poor
      setting, based on data from a pilot intervention of the 5S program implemented in
      a health facility in Senegal. DESIGN: In this qualitative study, we interviewed
      21 health center staff members 1 year after the pilot intervention. We asked them
      about their views on the changes brought on by the 5S program in their workplace,
      daily routines, and services provided. We then transcribed interview records and
      organized the narrative information by emerging themes using thematic analysis in
      the coding process. RESULTS: Study participants indicated that, despite resource
      constraints and other demotivating factors present at the health center, the 5S
      program created changes in the work environment, including fewer unwanted items,
      improved orderliness, and improved labeling and directional indicators of service
      units. These efforts engendered changes in the quality of services (e.g. making
      services more efficient, patient-centered, and safe), and in the attitude and
      behavior of staff and patients. CONCLUSIONS: The pilot intervention of the 5S
      management method was perceived to have improved the quality of healthcare
      services and staff motivation in a resource-poor healthcare facility with a
      disorderly work environment in Senegal. Quantitative and qualitative research
      based on a larger-scale intervention would be needed to elaborate and validate
      these findings and to identify the cost-effectiveness of such intervention in low
      and middle-income countries.

PMID- 25854782
TI  - Protonated Hexaazamacrocycles as Selective K(+) Receptors.
AB  - Protonated hexaazamacrocycle [M*H](+) is able to detect K(+) ions present at ppb
      level in methanolic solutions containing 10(-5) M of Na(+) ions. The high
      sensitivity and selectivity of [M*H](+) for K(+) is ascribed to the favorable
      energy balance between the K(+) ion desolvation and its coordination to the
      [M*H](+) macrocycle, which allows the formation of the corresponding adduct
      before the Coulombic explosion of the ESI-MS nanodroplets.

PMID- 25854784
TI  - Replacing soybean meal for wet brewer's grains or urea on the performance of
      lactating dairy cows.
AB  - The purpose of this research was to evaluate the partial replacement of soybean
      meal (SBM) for wet brewer's grains (WBG) or urea on the performance of lactating
      dairy cows. The second investigated whether WBG ensiled with corn kept animal
      performance in low- and high-producing dairy cows compared with WBG. In
      experiment I, 40 Holstein cows were used in 4 * 4 Latin square design. The
      treatments comprised WBG or urea as partial replacement for SBM, as follows:
      control (diet based on SBM and 1 % of urea), 10 % of WBG, 20 % of WBG, and 2 % of
      urea. Dry matter intake (DMI) was not affected by treatments. WBG increased milk
      yield linearly, but it decreased with urea. Milk fat content responded
      quadratically to WBG levels. Milk protein content decreased, while plasma urea
      nitrogen increased with high urea addition. In experiment II, 42 Holstein cows
      were divided into two groups according to production levels. Eighteen cows
      composed the group of low producing, while the high-producing group comprised 24
      cows. The experimental design was a crossover with two periods of 14 days. The
      experimental treatments consisted of feeding WBG or WBG ensiled with ground corn.
      Regardless of the production level, no difference in milk yield and milk
      composition between treatments was observed. 

PMID- 25854785
TI  - Leisure time physical activity before and during mid-pregnancy and offspring
      adiposity in mid-childhood.
AB  - BACKGROUND: Effects of maternal leisure time physical activity (LTPA) on
      paediatric obesity are unknown. The objective of this study was to examine
      associations of maternal LTPA with offspring overall and central adiposity in mid
      childhood. METHODS: We analysed data from 802 mother-child dyads from Project
      Viva, a prospective pre-birth cohort study. Women reported average weekly LTPA
      before and during mid-pregnancy. At age 7-10 years, we measured fat, truncal fat
      and lean mass with dual-energy X-ray absorptiometry. Using multivariable linear
      regression, we examined associations of maternal LTPA with offspring adiposity,
      adjusting for child age and sex, maternal race/ethnicity, education, age, pre
      pregnancy body mass index, marital status and smoking status. RESULTS: Mean
      (standard deviation) of LTPA before and during mid-pregnancy were 9.5 (8.1) and
      7.1 (7.0) h week(-1) . At mean age 7.8 (0.8) years, childhood fat, truncal fat
      and lean mass indices were 4.3 (1.8), 1.4 (0.8) and 12.9 (1.4) kg m(-2) . We did
      not find that higher maternal LTPA was associated with lower child adiposity
      outcomes. For example, compared with 0-3 h week(-1) of LTPA during mid-pregnancy,
      children of mothers with +8 h week(-1) had fat mass index 0.07 kg m(-2) (95%
      confidence interval: -0.22, 0.36). In analyses of within-person LTPA change from
      before to mid-pregnancy, compared with +2 h week(-1) decrease in LTPA, increased
      LTPA (2 +/- h week(-1) ) was associated with a 0.09 kg m(-2) fat mass index (
      0.25, 0.43). CONCLUSIONS: Contrary to our hypothesis, higher LTPA before and
      during mid-pregnancy, and the change between them, were not associated with lower
      adiposity in mid-childhood.

PMID- 25854786
TI  - Coenzyme Q10 in combination with triple therapy regimens ameliorates oxidative
      stress and lipid peroxidation in chronic gastritis associated with H. pylori
      infection.
AB  - Chronic gastritis associated with H. pylori infection causes oxidative stress in
      the stomach. This study aimed to evaluate the therapeutic effects of coenzyme q10
      among gastric patients infected by H. pylori. By a clinical trial, chronic
      gastric patients infected by H. pylori were randomly divided into 2 groups:
      intervention and placebo. The placebo group received a standard triple therapy
      regimen, and the intervention group received the triple regimen + coenzyme Q10
      (CoQ10). Mean inflammation score; serum levels of 3 serum markers were then
      compared. A total of 100 participants of whom 67% were female were evaluated. The
      mean age of participants was 59.4 +/- 11.4 years. The mean inflammation score was
      considerably decreased at the end of the study, in the intervention group. The
      mean levels of total antioxidant capacity (TAC) and glutathione peroxidase (GPx)
      at the end of the study were reduced among the triple therapy group (P < .05, P
      =.03 respectively). The mean levels of TAC and GPx were significantly higher
      among the intervention group at the end of the study compared with those at the
      start of the study. The combination of triple therapy with CoQ10 demonstrated an
      effective outcome on the mucosal inflammation, and stress oxidative in patients
      with chronic gastritis.

PMID- 25854787
TI  - Measurement of body temperature in 300 dogs with a novel noncontact infrared
      thermometer on the cornea in comparison to a standard rectal digital thermometer.
AB  - OBJECTIVE: To assess the accuracy of obtaining body temperatures in dogs with a
      noncontact infrared thermometer (NCIT) on the cornea compared with a rectal
      digital thermometer (RDT). DESIGN: Prospective single center study. SETTING:
      University teaching hospital. ANIMALS: Three hundred dogs presented with low,
      normal, or high body temperatures. INTERVENTIONS: Three body temperature readings
      were measured by an RDT and by an NCIT on the cornea of the left eye by 2
      investigators (experienced and inexperienced). Results obtained by the 2 methods
      were compared. MEASUREMENTS AND MAIN RESULTS: Median body temperature measured by
      the experienced investigator with the RDT and the NCIT were 38.3 degrees C (range
      35.5 degrees C-41.1 degrees C; 95% CI: 38.2-38.4 degrees C) and 37.7 degrees C
      (35.9 degrees C-40.1 degrees C; 95% CI: 37.7 degrees C-37.9 degrees C),
      respectively. Measurement of RDT as well as of NCIT correlated well between both
      investigators (rRDT = 0.94; rNCIT = 0.82; respectively, P < 0.001 for both
      methods). Mean RDT and NCIT-temperature correlated poorly (r = 0.43; P < 0.001)
      when taken by the experienced investigator and even less by the nonexperienced
      investigator (r = 0.38; P < 0.001). Repeatability of the NCIT revealed an
      unsatisfactory value (0.24 degrees C) compared to RDT measurement (0.12 degrees
      C). Agreement between both devices in measuring low, normal, and high values,
      calculated by Cohens-Kappa, was unsatisfactory (k = 0.201; P < 0.001).
      Calculating the receiver operating characteristic curve to determine the best
      threshold for fever (defined as RDT temperature >39.0 degrees C) showed an area
      under the curve of 0.76. Mean discomfort score was significantly lower using NCIT
      compared to RDT measurement (P < 0.001). CONCLUSIONS: There was poor agreement
      between body temperatures obtained by RDT and NCIT. The corneal NCIT measurement
      tends to underrecognize hypothermic and hyperthermic conditions. Although the use
      of the NCIT yields faster results and is significantly more comfortable for the
      dog than the RDT measurement, it cannot be recommended in dogs at this time.

PMID- 25854788
TI  - Choosing the Best Newborn Anthropometric Measure Associated With the Risks and
      Outcomes of Intrauterine Growth Restriction.
AB  - Intrauterine growth restriction (IUGR) is associated with various prenatal risks
      and postnatal adverse outcomes. The aim of this study is to choose the most
      sensitive newborn anthropometric measure, which is closely associated with IUGR
      related risks and outcomes, to substitute IUGR after delivery. Data were obtained
      from the Collaborative Perinatal Project, a multicenter prospective cohort study
      in the United States from 1959 to 1976. Maternal heavy smoking and severe
      hypertensive disorders during pregnancy, neonatal polycythemia and hypothermia,
      low intelligence quotient (<70) at age 7 years were chosen as IUGR-related risks
      and outcomes. Eight anthropometric measures at birth were tested by logistic
      regression model. Birth weight-to-head circumference (W/HC) had the largest odds
      ratio (OR) for neonatal polycythemia (OR = 1.8, 95% confidence interval [CI] =
      1.5-2.0), severe hypertensive disorders (OR = 1.9, 95% CI = 1.5-2.2), and
      maternal heavy smoking (OR = 1.9, 95% CI = 1.7-2.1) during pregnancy. It also had
      the highest summary OR (9.3). Thus, W/HC may be a good measure for IUGR. 

PMID- 25854789
TI  - Proteomics data visualisation.

PMID- 25854793
TI  - Reactive oxygen species regulate programmed cell death progress of endosperm in
      winter wheat (Triticum aestivum L.) under waterlogging.
AB  - Previous studies have proved that waterlogging stress accelerates the programmed
      cell death (PCD) progress of wheat endosperm cells. A highly waterlogging
      tolerant wheat cultivar Hua 8 and a waterlogging susceptible wheat cultivar Hua 9
      were treated with different waterlogging durations, and then, dynamic changes of
      reactive oxygen species (ROS), gene expressions, and activities of antioxidant
      enzymes in endosperm cells were detected. The accumulation of ROS increased
      considerably after 7 days of waterlogging treatment (7 DWT) and 12 DWT in both
      cultivars compared with control group (under non-waterlogged conditions),
      culminated at 12 DAF (days after flowering) and reduced hereafter. Waterlogging
      resulted in a great increase of H2O2 and O2 (-) in plasma membranes, cell walls,
      mitochondrias, and intercellular spaces with ultracytochemical localization.
      Moreover, the deformation and rupture of cytomembranes as well as the swelling
      and distortion of mitochondria were obvious. Under waterlogging treatment
      conditions, catalase (CAT) gene expression increased in endosperm of Hua 8 but
      activity decreased. In addition, Mn superoxide dismutase (MnSOD) gene expression
      and superoxide dismutase (SOD) activity increased. Compared with Hua 8, both CAT,
      MnSOD gene expressions and CAT, SOD activities decreased in Hua 9. Moreover,
      ascorbic acid and mannitol relieve the intensifying of PCD processes in Hua 8
      endosperm cells induced by waterlogging. These results indicate that ROS have
      important roles in the PCD of endosperm cells, the changes both CAT, MnSOD gene
      expressions and CAT, SOD activities directly affected the accumulation of ROS in
      two different wheat cultivars under waterlogging, ultimately led to the PCD
      acceleration of endosperm.

PMID- 25854794
TI  - Presence of hyperalgesia predicts analgesic efficacy of topically applied
      capsaicin 8% in patients with peripheral neuropathic pain.
AB  - BACKGROUND: Topical high-dose capsaicin acting on TRPV1 receptors and inducing an
      intraepidermal decrease in the small nerve fibre count is effective in treating
      neuropathic pain (NP). Sensory changes after capsaicin application, their
      correlation with pain relief and their role as possible predictors of response
      have been insufficiently analysed. We hypothesized a positive correlation between
      pain relief and increase in the warmth detection threshold (WDT), indicating loss
      of C-fibre function, and higher response rates in patients with preserved C-fibre
      function or heat hyperalgesia before application. METHODS: Quantitative Sensory
      Testing (DFNS protocol) was conducted in 20 unilaterally treated patients with
      peripheral NP (peripheral nerve injury: n = 14, polyneuropathy: n = 4,
      postherpetic neuralgia: n = 2) before and 2, 4, 6 and 8 weeks after application
      of capsaicin (8%) in this open-label study. Response was defined as >=30% or >=2
      (Numeric Rating Scale: 0-10) decrease of current pain at any follow-up compared
      to baseline. RESULTS: In all patients, WDT significantly increased 8 weeks after
      capsaicin application, but did not correlate with pain relief in responders (n =
      10, r = 0.179, p = 0.141). Before treatment, responders showed significantly
      higher z-values for the cold (CPT, +0.7 +/- 1.1 vs. -0.4 +/- 0.9) and mechanical
      pain threshold (MPT; 0.7 +/- 2.5 vs. -1.2 +/- 1.3), but did not differ from non
      responders regarding WDT or heat pain threshold. A sum of the z-values for CPT
      and MPT >0.8 before treatment identified responders with 100% specificity and 70%
      sensitivity. CONCLUSIONS: Efficacy of capsaicin does not correlate with the
      induced loss of function of small fibres, measured by QST. Presence of cold and
      pinprick hyperalgesia seems to be predictive of response to capsaicin (8%).

PMID- 25854795
TI  - Successful management of a distal vessel perforation through a single 8-French
      guide catheter: Combining balloon inflation for bleeding control with coil
      embolization.
AB  - Coronary perforation is an infrequent, but serious complication of percutaneous
      coronary intervention (PCI), and is more likely to occur with complex (such as
      chronic total occlusion) PCI and use of atheroablative devices. For main vessel
      perforations, the "dual catheter" technique is usually employed in which a
      balloon is delivered over the first guide catheter to stop bleeding, whereas the
      covered stent is delivered through a second guide catheter. This is required
      because the large profile of the currently commercially available covered stents
      precludes fitting within even an 8-French guide together with a balloon. However,
      coil embolization for distal artery wire perforation and collateral vessel
      perforation can be achieved through a microcatheter that can fit along with a
      balloon within an 8-French guide catheter, obviating the need for a second guide
      catheter. We describe a case in which a distal artery wire perforation was
      successfully treated using a single 8-French guide catheter.

PMID- 25854796
TI  - beta-blocker use and mortality in COPD patients after myocardial infarction: a
      Swedish nationwide observational study.
AB  - BACKGROUND: Patients with myocardial infarction (MI) and concomitant chronic
      obstructive pulmonary disease (COPD) constitute a high-risk group with increased
      mortality. beta-Blocker therapy has been shown to reduce mortality, prevent
      arrhythmias, and delay heart failure development after an MI in broad
      populations. However, the effect of beta-blockers in COPD patients is less well
      established and they may also be less treated due to fear of adverse reactions.
      We investigated beta-blocker prescription at discharge in patients with COPD
      after MI. METHODS AND RESULTS: Patients hospitalized for MI between 2005 and 2010
      were identified from the nationwide Swedish SWEDEHEART registry. Patients with
      COPD who were alive and discharged after an MI were selected as the study
      population. In this cohort, patients who were discharged with beta-blockers were
      compared to patients not discharged with beta-blockers. The primary end point was
      all-cause mortality. A total of 4858 patients were included, of which 4086
      (84.1%) were discharged with a beta-blocker while 772 (15.9%) were not. After
      adjusting for potential confounders including baseline characteristics,
      comorbidities, and in-hospital characteristics, patients discharged with a beta
      blocker had lower all-cause mortality (hazard ratio 0.87, 95% CI 0.78 to 0.98)
      during the total follow-up time (maximum 7.2 years). In the subgroup of patients
      with a history of heart failure, the corresponding hazard ratio was 0.77 (95% CI
      0.63 to 0.95). CONCLUSIONS: Patients with COPD discharged with beta-blockers
      after an MI had a lower all-cause mortality compared to patients not prescribed
      beta-blockers. The results indicate that MI patients with COPD may benefit from
      beta-blockers.

PMID- 25854797
TI  - Transformation of the title V maternal and child health services block grant.
AB  - This paper describes the transformation of the Title V Maternal and Child Health
      (MCH) Services Block Grant. The Maternal and Child Health Bureau of the Health
      Resources and Services Administration led a 21-month visioning process to engage
      input from MCH stakeholders and other national, state and local MCH leaders,
      families and other partners to improve, innovate, and transform the Title V MCH
      Services Block Grant. The process has helped inform the development of a new
      grant guidance for the next 5-year cycle beginning in fiscal year 2016. The
      triple aims of the transformation are to reduce burden, maintain flexibility, and
      increase accountability. State reporting burden is reduced by aligning and
      streamlining the needs assessment, annual report and application, reducing the
      number of forms States have to fill out, eliminating Health Systems Capacity
      Indicators, and prepopulating the annual report and application with State data
      using national data sources. State flexibility is maintained through the needs
      assessment process whereby State needs and priorities drive the selection of
      National Performance Measures and State-specific Performance Measures, and the
      development of State Action Plan and Evidence-based/informed Strategy Measures.
      Accountability is increased through the new three-tiered performance measurement
      framework, which will help States tell a more coherent and compelling story about
      the impact of Title V on the health of the Nation's mothers, children, and
      families. The ultimate success of the transformation will be measured by how much
      the transformed Title V program moves the needle in MCH in the States and for the
      Nation.

PMID- 25854798
TI  - Moving attractive virtual agent improves interpersonal coordination stability.
AB  - Interpersonal motor coordination is influenced not only by biomechanical factors
      such as coordination pattern, oscillating frequency, and individual differences,
      but also by psychosocial factor such as likability and social competences. Based
      on the social stereotype of "what is beautiful is good", the present study aimed
      at investigating whether people coordinate differently with physically attractive
      people compared to less attractive people. 34 participants were engaged in an
      interpersonal coordination task with different looking (virtual) agents while
      performing at the same time a reaction time task. Results showed that
      participants had more stable motor coordination with the moving attractive than
      with the less attractive agent, and that the difference in motor coordination
      could not be interpreted by a specific attention allocation strategy. Our
      findings provide the evidence that physical attractiveness genuinely affects how
      people interact with another person, and that the temporal-spatial coordinated
      movement varies with the partner's psychosocial characteristics. The study
      broadens the perspective of exploring the effect of additional psychosocial
      factors on social motor coordination. 

PMID- 25854800
TI  - Controlled synthesis of monodisperse alpha-calcium sulfate hemihydrate
      nanoellipsoids with a porous structure.
AB  - We report a facile and green chemical solution approach to synthesize
      monodisperse alpha-calcium sulfate hemihydrate (alpha-HH) nanoellipsoids with a
      length of 600 nm and a width of 300 nm by simply mixing Ca(2+) and SO4(2-)
      glycerol-water precursor solutions in the presence of Na2EDTA. The alpha-HH
      nanoellipsoid is formed through a Na2EDTA-mediated self-assembly of small primary
      building blocks (alpha-HH domains: ~14 nm). The study on the morphological
      evolution of alpha-HH reveals that the controlled synergy of supersaturation
      (precursor concentration) and Na2EDTA is crucial for the development of alpha-HH
      into nanoellipsoids. Further thermal annealing of the nanoellipsoid could make
      the alpha-HH domains transit into calcium sulfate anhydrites and grow up,
      generating the gaps between them and resulting in a porous structure. This work
      paves a new way for preparing high-quality alpha-HH nanoellipsoids with a
      monodisperse nanosize and a porous structure, promising their future application
      in many fields such as biomedicine. 

PMID- 25854799
TI  - Identification of autonomic neuronal chains innervating gingiva and lip.
AB  - The major goals of this present study were 1) to further clarify which
      parasympathetic ganglion sends postganglionic fibers to the lower gingiva and lip
      that may be involved in the inflammatory processes besides the local factors; 2)
      to separately examine the central pathways regulating sympathetic and
      parasympathetic innervation; and 3) to examine the distribution of central
      premotor neurons on both sides. A retrogradely transported green fluorescent
      protein conjugated pseudorabies virus was injected into the lower gingiva and lip
      of intact and sympathectomized adult female rats. Some animals received virus in
      the adrenal medulla which receive only preganglionic sympathetic fibers to
      separately clarify the sympathetic nature of premotor neurons. After 72-120h of
      survival and perfusion, the corresponding thoracic part of the spinal cord,
      brainstem, hypothalamus, cervical, otic, submandibular and trigeminal ganglia
      were harvested. Frozen sections were investigated under a confocal microscope.
      Green fluorescence indicated the presence of the virus. The postganglionic
      sympathetic neurons related to both organs are located in the three cervical
      ganglia, the preganglionic neurons in the lateral horn of the spinal cord on
      ipsilateral side; premotor neurons were found in the ventrolateral medulla, locus
      ceruleus, gigantocellular and paraventricular nucleus and perifornical region in
      nearly the same number on both sides. The parasympathetic postganglionic neurons
      related to the gingiva are present in the otic and related to the lip are present
      in the otic and submandibular ganglia and the preganglionic neurons are in the
      salivatory nuclei. Third order neurons were found in the gigantocellular
      reticular and hypothalamic paraventricular nuclei and perifornical area.

PMID- 25854801
TI  - Association between ICS POP-Q coordinates and translabial ultrasound findings:
      implications for definition of 'normal pelvic organ support'.
AB  - OBJECTIVES: Female pelvic organ prolapse is quantified on clinical examination
      using the pelvic organ prolapse quantification system of the International
      Continence Society (ICS POP-Q). Pelvic organ descent on ultrasound is strongly
      associated with symptoms of prolapse, but associations between clinical and
      ultrasound findings remain unclear. This study was designed to compare clinical
      examination and imaging findings, especially regarding cut-offs for the
      distinction between normal pelvic organ support and prolapse. METHODS: This was a
      retrospective study using 839 archived datasets of women referred to a tertiary
      urogynecological center for symptoms of lower urinary tract and pelvic floor
      dysfunction between June 2011 and May 2013. The main outcome measures were the
      maximum downward displacement of the anterior vaginal wall (point Ba), the cervix
      (point C) and the posterior vaginal wall (point Bp), the length of the genital
      hiatus (Gh) and the length of the perineal body (Pb), as defined by the ICS POP
      Q; explanatory parameters were measures of pelvic organ descent on translabial
      ultrasound, ascertained by offline volume data analysis at a later date, by an
      operator blinded to all other data. RESULTS: Full datasets were available for 825
      women. On clinical examination, 646 (78.3%) were found to have prolapse of at
      least POP-Q Stage 2. All coordinates on clinical examination were strongly
      associated with the ultrasound measurements of pelvic organ descent (P < 0.001).
      These relationships were almost linear, especially for the anterior compartment.
      CONCLUSIONS: There is a near linear relationship between sonographic and clinical
      measures of prolapse. Previously proposed cut-offs to define 'significant
      prolapse' on ultrasound and POP-Q (Ba >= -0.5 and cystocele >= 10 mm below the
      symphysis pubis, C >= -5 and uterine position of 15 mm above the symphysis pubis,
      Bp >= -0.5 and rectocele >= 15 mm below the symphysis pubis) are plausible and
      mutually consistent. Copyright (c) 2015 ISUOG. Published by John Wiley & Sons
      Ltd.

PMID- 25854802
TI  - Pru du 2S albumin or Pru du vicilin?
AB  - A short partial sequence of 28 amino acids is all the information we have so far
      about the putative allergen 2S albumin from almond. The aim of this work was to
      analyze this information using mainly bioinformatics tools, in order to verify
      its rightness. Based on the results reported in the paper describing this
      allergen from almond, we analyzed the original data of amino acids sequencing
      through available software. The degree of homology of the almond 12kDa protein
      with any other known 2S albumin appears to be much lower than the one reported in
      the paper that firstly described it. In a publicly available cDNA library we
      discovered an expressed sequence tag which translation generates a protein that
      perfectly matches both of the sequencing outputs described in the same paper. A
      further analysis indicated that the latter protein seems to belong to the vicilin
      superfamily rather than to the prolamin one. The fact that also vicilins are seed
      storage proteins known to be highly allergenic would explain the IgE reactivity
      originally observed. Based on our observations we suggest that the IgE reactive
      12kDa protein from almond currently known as Pru du 2S albumin is in reality the
      cleaved N-terminal region of a 7S vicilin like protein. 

PMID- 25854803
TI  - Evaluation of the effect of the chiral centers of Taxol on binding to beta
      tubulin: A docking and molecular dynamics simulation study.
AB  - Taxol is one of the most important anti-cancer drugs. The interaction between
      different variants of Taxol, by altering one of its chiral centers at a time,
      with beta-tubulin protein has been investigated. To achieve such goal, docking
      and molecular dynamics (MD) simulation studies have been performed. In docking
      studies, the preferred conformers have been selected to further study by MD
      method based on the binding energies reported by the AutoDock program. The best
      result of docking study which shows the highest affinity between ligand and
      protein has been used as the starting point of the MD simulations. All of the
      complexes have shown acceptable stability during the simulation process, based on
      the RMSDs of the backbone of the protein structure. Finally, MM-GBSA calculations
      have been carried out to select the best ligand, considering the binding energy
      criteria. The results predict that two of the structures have better affinity
      toward the mentioned protein, in comparison with Taxol. Three of the structures
      have affinity similar to that of the Taxol toward the beta-tubulin. 

PMID- 25854804
TI  - Exploring the relationship between hub proteins and drug targets based on GO and
      intrinsic disorder.
AB  - Protein-protein interactions (PPIs) play essential roles in many biological
      processes. In protein-protein interaction networks, hubs involve in numbers of
      PPIs and may constitute an important source of drug targets. The intrinsic
      disorder proteins (IDPs) with unstable structures can promote the promiscuity of
      hubs and also involve in many disease pathways, so they also could serve as
      potential drug targets. Moreover, proteins with similar functions measured by
      semantic similarity of gene ontology (GO) terms tend to interact with each other.
      Here, the relationship between hub proteins and drug targets based on GO terms
      and intrinsic disorder was explored. The semantic similarities of GO terms and
      genes between two proteins, and the rate of intrinsic disorder residues of each
      protein were extracted as features to characterize the functional similarity
      between two interacting proteins. Only using 8 feature variables, prediction
      models by support vector machine (SVM) were constructed to predict PPIs. The
      accuracy of the model on the PPI data from human hub proteins is as high as
      83.72%, which is very promising compared with other PPI prediction models with
      hundreds or even thousands of features. Then, 118 of 142 PPIs between hubs are
      correctly predicted that the two interacting proteins are targets of the same
      drugs. The results indicate that only 8 functional features are fully efficient
      for representing PPIs. In order to identify new targets from IDP dataset, the
      PPIs between hubs and IDPs are predicted by the SVM model and the model yields a
      prediction accuracy of 75.84%. Further research proves that 3 of 5 PPIs between
      hubs and IDPs are correctly predicted that the two interacting proteins are
      targets of the same drugs. All results demonstrate that the model with only 8
      dimensional features from GO terms and intrinsic disorder still gives a good
      performance in predicting PPIs and further identifying drug targets. 

PMID- 25854805
TI  - Screening and vaccinations in patients requiring systemic immunosuppression: an
      update for dermatologists.
AB  - Immunomodulatory agents are becoming an increasingly important tool in the
      dermatologist's armamentarium against autoimmune and auto-inflammatory
      conditions. This review addresses the guidelines for vaccination and screening
      studies prior to the initiation of immunomodulatory agents. Included are
      discussions of vaccination schedules, hepatitis vaccination and screening,
      tuberculosis screening, and specific screening recommendations for antimalarials,
      azathioprine, cyclosporine, methotrexate, mycophenolate mofetil, tumor necrosis
      factor-alpha inhibitors, and newer medications like apremilast and tofacitinib. 

PMID- 25854806
TI  - Cd11b(+) myeloid cells support hepatic metastasis through down-regulation of
      angiopoietin-like 7 in cancer cells.
AB  - Myeloid cells are known to mediate metastatic progression. Here, we attempted to
      elucidate the mechanisms underlying these effects by identifying gene expression
      alterations in cancer cells forming hepatic metastases after myeloid cell
      depletion. Hepatic metastases are heavily infiltrated by CD11b(+) myeloid cells.
      We established hepatic metastases in transgenic CD11b-diphtheria toxin receptor
      mice by intrasplenic injection of MC38 colon and Lewis lung carcinoma cells
      before depleting myeloid cells with diphtheria toxin. Myeloid cell depletion
      inhibited metastatic growth with a marked diminishment of tumor vasculature.
      Expression of ANGPTL7 (angiopoietin-like 7), a protein not previously linked to
      metastasis, was highly up-regulated in cancer cells after myeloid cell depletion.
      This effect was duplicated in tissue culture, where coculture of cancer cells
      with tumor-conditioned myeloid cells from liver metastases or myeloid cell
      conditioned media down-regulated ANGPTL7 expression. Analogous to myeloid cell
      depletion, overexpression of ANGPTL7 in cancer cells significantly reduced
      hepatic metastasis formation and angiogenesis. We found that ANGPTL7 itself has
      strong antiangiogenic effects in vitro. Furthermore, analysis of The Cancer
      Genome Atlas colorectal and breast cancer data sets revealed striking ANGPTL7
      underexpression in cancerous compared to normal tissues. Also, ANGPTL7 was down
      regulated in metastatic liver colonies of colorectal cancer patients compared to
      their adjacent liver tissue. CONCLUSION: Myeloid cells promote liver metastasis
      by down-regulating ANGPTL7 expression in cancer cells; our findings implicate
      ANGPTL7 as a mediator of metastatic progression and a potential target for
      interference with liver metastases.

PMID- 25854807
TI  - 1H and 13C NMR assignments of new ecdysteroids from Callisia fragrans.

PMID- 25854808
TI  - Expression-level dependent perturbation of cell proteostasis and nuclear
      morphology by aggregation-prone polyglutamine proteins.
AB  - We describe a gene expression system for use in mammalian cells that yields
      reproducible, inducible gene expression that can be modulated within the
      physiological range. A synthetic promoter library was generated from which
      representatives were selected that gave weak, intermediate-strength or strong
      promoter activity. Each promoter resulted in a tight expression range when used
      to drive single-copy reporter genes integrated at the same genome location in
      stable cell lines, in contrast to the broad range of expression typical of
      transiently transfected cells. To test this new expression system in
      neurodegenerative disease models, we used each promoter type to generate cell
      lines carrying single-copy genes encoding polyglutamine-containing proteins.
      Expression over a period of up to three months resulted in a proportion of cells
      developing juxtanuclear aggresomes whose rate of formation, penetrance, and
      morphology were expression-level dependent. At the highest expression levels,
      fibrillar aggregates deposit close to the nuclear envelope, indicating that cell
      proteostasis is overwhelmed by misfolded protein species. We also observed
      expression-level dependent, abnormal nuclear morphology in cells containing
      aggresomes, with up to ~80% of cells affected. This system constitutes a valuable
      tool in gene regulation at different levels and allows the quantitative
      assessment of gene expression effects when developing disease models or
      investigating cell function through the introduction of gene constructs.

PMID- 25854810
TI  - Design, fabrication and analysis of stagnation flow microreactors used to study
      hypergolic reactions.
AB  - A novel method to study the condensed phase reactions that occur during the
      ignition of hypergolic propellants (very fast liquid reactions) using
      microreactors is presented. Planar counterflow microreactors are used to isolate
      liquid-phase reactions and diffusion from secondary gas-phase chemical and
      transport processes that often occur concurrently during the overall ignition
      process. The counterflow microreactor has made it possible to achieve valuable
      insight into the preignition mechanisms of hypergolic propellants hitherto not
      possible using conventional drop or impinging jet tests. In the present paper,
      the microreactor fabrication, flow field characterization, and reactivity of 2
      dimethylaminoethylazide and nitric acid as hypergols are presented. Particle
      image velocimetry and numerical simulations were conducted to characterize the
      laminar velocity flow-field from which stagnation point strain rates and contact
      residence times along the centerline of the microreactor were evaluated.
      Temperature measurements at the exit of the reactor (as well as at the stagnation
      point) were used as a measure for the extent of the reaction or the heat released
      from the reaction. For the hypergols, an increase in reactant flow (or
      equivalently strain rate at the stagnation point) was found to initially increase
      reactivity, but eventually resulted in a decrease in temperature, revealing a
      maxima in temperature and reactivity. The trends indicated a reaction that was
      initially diffusion or heat loss controlled, which transitioned towards kinetic
      control at higher strain (flow) rates. This paper details the first comprehensive
      measurements and analysis of the effects of diffusion based mixing on the
      interfacial reactions occurring between hypergols. 

PMID- 25854809
TI  - Economic evaluation of occupational therapy in Parkinson's disease: A randomized
      controlled trial.
AB  - BACKGROUND: A large randomized clinical trial (the Occupational Therapy in
      Parkinson's Disease [OTiP] study) recently demonstrated that home-based
      occupational therapy improves perceived performance in daily activities of people
      with Parkinson's disease (PD). The aim of the current study was to evaluate the
      cost-effectiveness of this intervention. METHODS: We performed an economic
      evaluation over a 6-month period for both arms of the OTiP study. Participants
      were 191 community-dwelling PD patients and 180 primary caregivers. The
      intervention group (n = 124 patients) received 10 weeks of home-based
      occupational therapy; the control group (n = 67 patients) received usual care (no
      occupational therapy). Costs were assessed from a societal perspective including
      healthcare use, absence from work, informal care, and intervention costs. Health
      utilities were evaluated using EuroQol-5d. We estimated cost differences and cost
      utility using linear mixed models and presented the net monetary benefit at
      different values for willingness to pay per quality-adjusted life-year gained.
      RESULTS: In our primary analysis, we excluded informal care hours because of
      substantial missing data for this item. The estimated mean total costs for the
      intervention group compared with controls were ?125 lower for patients, ?29 lower
      for caregivers, and ?122 higher for patient-caregiver pairs (differences not
      significant). At a value of ?40,000 per quality-adjusted life-year gained
      (reported threshold for PD), the net monetary benefit of the intervention per
      patient was ?305 (P = 0.74), per caregiver ?866 (P = 0.01) and per patient
      caregiver pair ?845 (P = 0.24). CONCLUSION: In conclusion, occupational therapy
      did not significantly impact on total costs compared with usual care. Positive
      cost-effectiveness of the intervention was only significant for caregivers.

PMID- 25854811
TI  - Total ankle arthroplasty in patients with inherited bleeding disorders.

PMID- 25854812
TI  - Dimensional metrology of lab-on-a-chip internal structures: a comparison of
      optical coherence tomography with confocal fluorescence microscopy.
AB  - The characterization of internal structures in a polymeric microfluidic device,
      especially of a final product, will require a different set of optical metrology
      tools than those traditionally used for microelectronic devices. We demonstrate
      that optical coherence tomography (OCT) imaging is a promising technique to
      characterize the internal structures of poly(methyl methacrylate) devices where
      the subsurface structures often cannot be imaged by conventional wide field
      optical microscopy. The structural details of channels in the devices were imaged
      with OCT and analyzed with an in-house written ImageJ macro in an effort to
      identify the structural details of the channel. The dimensional values obtained
      with OCT were compared with laser-scanning confocal microscopy images of channels
      filled with a fluorophore solution. Attempts were also made using confocal
      reflectance and interferometry microscopy to measure the channel dimensions, but
      artefacts present in the images precluded quantitative analysis. OCT provided the
      most accurate estimates for the channel height based on an analysis of optical
      micrographs obtained after destructively slicing the channel with a microtome.
      OCT may be a promising technique for the future of three-dimensional metrology of
      critical internal structures in lab-on-a-chip devices because scans can be
      performed rapidly and noninvasively prior to their use. 

PMID- 25854813
TI  - mTOR expression correlates with invasiveness and progression of extramammary
      Paget's disease.

PMID- 25854814
TI  - Risk Stratification of Acute Kidney Injury Using the Blood Urea
      Nitrogen/Creatinine Ratio in Patients With Acute Decompensated Heart Failure.
AB  - BACKGROUND: Risk stratification of acute kidney injury (AKI) is important for
      acute decompensated heart failure (ADHF). The aim of this study was to determine
      whether clinical markers, such as the blood urea nitrogen/creatinine ratio
      (BUN/Cr) or BUN or creatinine values alone, stratify the risk of AKI for
      mortality. METHODS AND RESULTS: In all, 371 consecutive ADHF patients were
      enrolled in the study. AKI was defined as serum creatinine >=0.3 mg/dl or a 1.5
      fold increase in serum creatinine levels within 48 h. During ADHF therapy, AKI
      occurred in 99 patients; 55 patients died during the 12-month follow-up period.
      Grouping patients according to AKI and a median BUN/Cr at admission of 22.1 (non
      AKI+low BUN/Cr, non-AKI+high BUN/Cr, AKI+low BUN/Cr, and AKI+high BUN/Cr groups)
      revealed higher mortality in the AKI+high BUN/Cr group (log-rank test, P<0.001).
      Cox's proportional hazard analysis revealed an association between AKI+high
      BUN/Cr and mortality, whereas the association with AKI+low BUN/Cr did not reach
      statistical significance. When patients were grouped according to AKI and median
      BUN or creatinine values at admission, AKI was associated with mortality,
      regardless of BUN or creatinine. CONCLUSIONS: The combination of AKI and elevated
      BUN/Cr, but not BUN or creatinine individually, is linked with an increased risk
      of mortality in ADHF patients, suggesting that the BUN/Cr is useful for risk
      stratification of AKI.

PMID- 25854815
TI  - CD45 antigen negativity in T-lineage ALL correlates with PTPRC mutation and
      sensitivity to a selective JAK inhibitor.

PMID- 25854817
TI  - In pursuit of neuroimaging biomarkers to guide treatment selection in major
      depressive disorder: a review of the literature.
AB  - Over the last few decades, neuroimaging techniques have advanced the
      identification of structural, functional, and neurochemical brain abnormalities
      that are associated with the increased risk, clinical course, and treatment
      outcomes of major depressive disorder (MDD). This paper reviews specific
      neuroimaging abnormalities that, on the basis of early studies, may discriminate
      between MDD patients who do or do not respond to current therapeutic modalities,
      such as antidepressants, cognitive behavioral therapy, or novel therapies.
      Differences in gray matter volume, white matter coherence, brain activity via
      structural and functional magnetic resonance imaging techniques, and
      concentrations of specific brain metabolites (as measured with magnetic resonance
      spectroscopy), are potential biomarkers discussed in this review. Given the
      heterogeneity of MDD, larger, multisite studies with increased statistical power
      will be needed to identify more precise imaging biomarkers of treatment response
      in MDD. 

PMID- 25854818
TI  - Efficacy and safety of electroconvulsive therapy in the first trimester of
      pregnancy: a case of severe manic catatonia.
AB  - OBJECTIVES: Electroconvulsive therapy (ECT) is an appropriate, albeit often
      neglected, option for managing severe or life-threatening psychiatric symptoms
      during pregnancy. We report on the rapid effectiveness and safety of ECT during
      the first trimester of pregnancy in a 28-year-old woman with severe catatonia.
      METHODS: Catatonic symptoms were assessed using the Catatonia Rating Scale (CRS).
      The patient was treated with unilateral ECT using left anterior right temporal
      (LART) placement. Seizure quality and duration were monitored by a two-lead
      electroencephalograph (EEG) and by one-lead electromyography (EMG). During each
      ECT session, the fetal heart rate was monitored with electrocardiogram (ECG).
      RESULTS: After the second ECT treatment (day 13 of hospitalization), we observed
      remission of the catatonic symptoms, as shown by the drop in the CRS score from
      22 to 0. No cognitive abnormalities were reported and no gynecological
      complications were detected (e.g. vaginal bleeding, abdominal pain, or uterine
      contraction). The patient delivered at term a healthy male neonate who presented
      normal growth as well as normal psychomotor development. CONCLUSIONS: This case
      highlights the effectiveness of ECT in treating severe catatonic mania during the
      first 3 months of pregnancy. In addition, ECT proved to be a safe therapeutic
      option, since neither mother nor infant experienced any adverse event. We suggest
      that ECT might be considered as a valid and safe option in the therapeutic
      decision-making process when catatonic symptoms manifest during pregnancy.

PMID- 25854819
TI  - Electroconvulsive-therapy-associated neutropenia in treatment-resistant
      schizophrenia: Three case reports.

PMID- 25854820
TI  - Effects of insulin-like growth factor-1 on the relaxation responses of the
      cavernous smooth muscle from aged rats.
AB  - OBJECTIVE: The aim of this study was determine whether intracavernosal injection
      (ICI) of insulin-like growth factor-1 (IGF-1) protein can improve corpus
      cavernosal smooth muscle relaxation in aging rats. MATERIALS AND METHODS: Ten
      young (4-month-old) and 30 old (24-month-old) Sprague-Dawley male rats were
      enrolled in the study. The old rats were divided into three groups: vehicle-only
      (n = 10), IGF-1 1 ug/kg (n = 10) and IGF-1 10 ug/kg treatment groups (n = 10).
      After 4 weeks of single IGF-1 injection treatment, strips of corporal tissue were
      precontracted with phenylephrine, and dose-response curves were generated to
      evaluate endothelial-dependent [acetylcholine (ACh)], endothelial-independent
      [sodium nitroprusside (SNP)] and electrical field stimulation (EFS)
      vasoreactivity. The changes in percentage of cavernosal smooth muscle and the
      concentration of nitric oxide (NO) in penile tissue were also evaluated. RESULTS:
      After IGF-1 treatment, the vasoreactivity was significantly improved in both the
      1 ug/kg and the 10 ug/kg treatment groups compared with the vehicle-only group at
      4 weeks in response to ACh, SNP and EFS (all p < 0.05). The percentage of
      cavernosal smooth muscle was increased in the IGF-1 treatment groups. The NO
      concentrations were increased after IGF-1 treatment. CONCLUSIONS: These data
      demonstrate that ICI of IGF-1 can improve vasoreactivity via endothelium
      dependent and endothelial-independent mechanisms in the corpus cavernosum of the
      aging rat.

PMID- 25854821
TI  - Macrodystrophia lipomatosa in a healthy newborn.

PMID- 25854822
TI  - Pulmonary air leak associated with CPAP at term birth resuscitation.
AB  - OBJECTIVE: The Japan Resuscitation Council (JRC) Guidelines 2010 for neonatal
      resuscitation introduced continuous positive airway pressure (CPAP) in delivery
      room. The present study evaluated the effect of CPAP for pulmonary air leak at
      term birth. DESIGN, SETTING AND PATIENTS: This retrospective single-centre study
      used the data of term neonates who were born without major congenital anomalies
      at our centre between 2008 and 2009, and between 2011 and 2012. INTERVENTIONS:
      Resuscitation according to the JRC Guidelines 2010. MAIN OUTCOME MEASURES: We
      examined the association between the JRC Guidelines 2010, CPAP by face mask and
      pulmonary air leak. RESULTS: A total of 5038 infants were analysed. The frequency
      of CPAP by face mask increased after the update of the JRC Guidelines in 2010
      (1.7% vs 11.1%; p<0.001). Pulmonary air leak increased at early term (37 weeks:
      1.0% vs 3.5%, p=0.02; 38 weeks: 0.7% vs 2.2%, p=0.02). While adjusting for
      confounders, the JRC Guidelines 2010 was associated with pulmonary air leak in
      early-term neonates (37 weeks: adjusted OR (aOR) 4.37; 95% CI 1.40 to 17.45; 38
      weeks: aOR 2.80; 95% CI 1.04 to 8.91), but this association disappeared while
      adjusting for face mask CPAP additionally (37 weeks: aOR 1.90; 95% CI 0.47 to
      8.71; 38 weeks: aOR 1.66; 95% CI 0.54 to 5.77). CONCLUSIONS: Following the update
      of the JRC guidelines on neonatal resuscitation, we observed an increased use of
      CPAP via face mask, which was associated with a higher prevalence of pulmonary
      air leak in early-term neonates in our centre.

PMID- 25854823
TI  - Transaortic Transcatheter Aortic Valve Implantation as a Second Choice over the
      Transapical Access.
AB  - BACKGROUND AND AIMS: In this report, we present our experience with the
      transaortic transcatheter aortic valve implantation using the SAPIEN valve. The
      procedural success, 30-day outcome, and survival up to 2 years are compared with
      the transapical access performed in patients in our institution. MATERIAL AND
      METHODS: Of a total of 282 transcatheter aortic valve implantation patients, 100
      consecutive patients had a non-transfemoral approach. The transaortic and
      transapical access routes were used in 36 and 64 patients, respectively. The
      transaortic group had a higher mean logistic EuroSCORE (32.6 vs 25.2, p = 0.021)
      and more patients with left ventricular ejection fraction less than 40% (33.3% vs
      14.1%, p = 0.023). RESULTS: The respective technical success rates for the
      transaortic and transapical groups were 100% and 95.2% (p = NS). There were
      significantly more perioperative hemodynamic problems necessitating
      cardiopulmonary resuscitation or mechanical circulatory support in the
      transapical group (18.8% vs 2.8%, p = 0.023). The transaortic group had a
      slightly shorter hospital stay (7 vs 8 days, p = 0.018). The 30-day mortality was
      8.6% and 10.9% in the transaortic and transapical group, respectively (p = NS).
      Combined safety outcome was similar in both groups at 30 days. The respective 1
      year survival rates for the transaortic and transapical groups were 71.5% and
      68.3%, respectively (p = NS). CONCLUSION: The trans transcatheter aortic valve
      implantation is a considerable choice to transapical approach. Despite a higher
      risk patient cohort, the clinical outcome is at least comparable to the
      transapical transcatheter aortic valve implantation, and it can be utilized as a
      second choice for patients with prohibitive iliac-femoral anatomy for
      transfemoral access.

PMID- 25854825
TI  - Effectiveness of long-acting injectable antipsychotics: a clinical perspective.

PMID- 25854824
TI  - Activated pancreatic stellate cells can impair pancreatic islet function in mice.
AB  - BACKGROUND: Pancreatic or islet fibrosis is often associated with activated
      pancreatic stellate cells (PSCs). PSCs are considered not only to promote
      fibrosis, but also to be associated with glucose intolerance in some diseases. We
      therefore evaluated morphological and functional relationships between islets and
      PSCs in the normal mouse pancreas and transplanted islets. METHODS:
      Immunohistochemistry was used to map the presence of PSCs in the normal mouse
      pancreas and islets implanted under the renal capsule. We isolated and cultured
      mouse PSCs and characterized them morphologically by immunofluorescence staining.
      Furthermore, we measured their cytokine production and determined their effects
      on insulin release from simultaneously cultured islets. RESULTS: PSCs were
      scattered throughout the pancreas, with occasional cells within the islets,
      particularly in the islet capsule. In islet transplants they were found mainly in
      the graft periphery. Cultured PSCs became functionally activated and produced
      several cytokines. Throughout the culture period they linearly increased their
      production of interleukin-6 and mammalian keratinocyte-derived chemokine. PSC
      cytokine production was not affected by acute hyperglycemia. Syngeneic islets co
      cultured with PSCs for 24-48 h increased their insulin release and lowered their
      insulin content. However, short-term insulin release in batch-type incubations
      was unaffected after 48 h of co-culture. Increased islet cell caspase-3
      activation and a decreased islet cell replication were consistently observed
      after co-culture for 2 or 7 days. CONCLUSION: Activated PSCs may contribute to
      impaired islet endocrine function seen in exocrine pancreatitis and in islet
      fibrosis associated with some cases of type 2 diabetes.

PMID- 25854826
TI  - Relative efficacy of psychological and pharmacological treatments for social
      anxiety disorder.

PMID- 25854827
TI  - Development of mixed connective tissue disease and Sjogren's syndrome in a
      patient with trisomy X.
AB  - Increased risk of developing systemic lupus erythematosus (SLE) has been reported
      in patients with Klinefelter syndrome. Here, we describe a 16-year-old Japanese
      patient with trisomy X (47,XXX) who developed mixed connective tissue disease
      (MCTD) and Sjogren's syndrome. She had polyarthritis, edematous fingers with
      Raynaud's phenomenon, sicca syndrome, interstitial lung disease, possible
      myositis, and was positive for anti-nuclear antibody, anti-nRNP antibody and
      rheumatoid factor. This is the first report in the literature of a case of MCTD
      with female polysomy X, which further supports the link between the presence of
      extra X chromosome(s) and the development of autoimmune diseases. 

PMID- 25854828
TI  - Coexistence of systemic lupus erythematosus and familial Mediterranean fever.

PMID- 25854829
TI  - Characterization of damage in Portuguese lupus patients.

PMID- 25854830
TI  - Right atrial reduction plasty associated with the cox-maze procedure.
AB  - We performed a right atrial reduction plasty combined with the Cox-maze procedure
      in a patient with a giant right atrium and permanent atrial fibrillation. The
      reduction plasty involved excisions of the redundant atrial wall along two
      ablation lines of the maze procedure, and excision of the redundant thin septum
      primum. This procedure achieved a 60% dimension reduction and an 80% volume
      reduction. The reduced atrial size and sinus rhythm were maintained after 3.5
      years.

PMID- 25854831
TI  - Enteral nutrition in dementia: a systematic review.
AB  - The aim of this systematic review is to evaluate the role of enteral nutrition in
      dementia. The prevalence of dementia is predicted to rise worldwide partly due to
      an aging population. People with dementia may experience both cognitive and
      physical complications that impact on their nutritional intake. Malnutrition and
      weight loss in dementia correlates with cognitive decline and the progress of the
      disease. An intervention for long term eating difficulties is the provision of
      enteral nutrition through a Percutaneous Endoscopic Gastrostomy tube to improve
      both nutritional parameters and quality of life. Enteral nutrition in dementia
      has traditionally been discouraged, although further understanding of physical,
      nutritional and quality of life outcomes are required. The following electronic
      databases were searched: EBSCO Host, MEDLINE, PubMed, Cochrane Database of
      Systematic Reviews and Google Scholar for publications from 1st January 2008 and
      up to and including 1st January 2014. Inclusion criteria included the following
      outcomes: mortality, aspiration pneumonia, pressure sores, nutritional parameters
      and quality of life. Each study included separate analysis for patients with a
      diagnosis of dementia and/or neurological disease. Retrospective and prospective
      observational studies were included. No differences in mortality were found for
      patients with dementia, without dementia or other neurological disorders. Risk
      factors for poor survival included decreased or decreasing serum albumin levels,
      increasing age or over 80 years and male gender. Evidence regarding pneumonia was
      limited, although did not impact on mortality. No studies explored pressure sores
      or quality of life. 

PMID- 25854832
TI  - Applications of microencapsulated Bifidobacterium longum with Eleutherine
      americana in fresh milk tofu and pineapple juice.
AB  - Bifidobacterium longum was microencapsulated by extrusion technique and added in
      fresh milk tofu and pineapple juice. Microencapsulation of B. longum with
      Eleutherine americana extract, oligosaccharides extract, and commercial fructo
      oligosaccharides was assessed for the bacterial survival after sequential
      exposure to simulated gastric and intestinal juices, and refrigeration storage.
      Microencapsulated B. longum with the extract and oligosaccharides extract in the
      food products showed better survival than free cells under adverse conditions.
      Sensory analysis demonstrated that the products containing co-encapsulated
      bacterial cells were more acceptable by consumers than free cells. Pineapple
      juice prepared with co-encapsulated cells had lower values for over
      acidification, compared with the juice with free cells added. This work suggested
      that microencapsulated B. longum with E. americana could enhance functional
      properties of fresh milk tofu and pineapple juice. 

PMID- 25854834
TI  - Comment on: Pregnant Women's Preferences for Men's Faces Differ Significantly
      from Nonpregnant Women.

PMID- 25854835
TI  - Atomic layer deposition of Y2O3 on h-BN for a gate stack in graphene FETs.
AB  - The combination of h-BN and high-k dielectrics is required for a top gate
      insulator in miniaturized graphene field-effect transistors because of the low
      dielectric constant of h-BN. We investigated the deposition of Y(2)O(3) on h-BN
      using atomic layer deposition. The deposition of Y(2)O(3) on h-BN was confirmed
      without any buffer layer. An increase in the deposition temperature reduced the
      surface coverage. The deposition mechanism could be explained by the competition
      between the desorption and adsorption of the Y precursor on h-BN due to the
      polarization. Although a full surface coverage was difficult to achieve, the use
      of an oxidized metal seeding layer on h-BN resulted in a full surface coverage.

PMID- 25854833
TI  - Meta-analysis of the association between vitamin D and autoimmune thyroid
      disease.
AB  - Although emerging evidence suggests that low levels of vitamin D may contribute
      to the development of autoimmune disease, the relationship between vitamin D
      reduction and autoimmune thyroid disease (AITD), which includes Graves' disease
      (GD) and Hashimoto thyroiditis (HT), is still controversial. The aim was to
      evaluate the association between vitamin D levels and AITD through systematic
      literature review. We identified all studies that assessed the association
      between vitamin D and AITD from PubMed, Embase, CENTRAL, and China National
      Knowledge Infrastructure (CNKI) databases. We included studies that compared
      vitamin D levels between AITD cases and controls as well as those that measured
      the odds of vitamin D deficiency by AITD status. We combined the standardized
      mean differences (SMD) or the odds ratios (OR) in a random effects model. Twenty
      case-control studies provided data for a quantitative meta-analysis. Compared to
      controls, AITD patients had lower levels of 25(OH)D (SMD: -0.99, 95% CI: -1.31, 
      0.66) and were more likely to be deficient in 25(OH)D (OR 2.99, 95% CI: 1.88,
      4.74). Furthermore, subgroup analyses result showed that GD and HT patients also
      had lower 25(OH)D levels and were more likely to have a 25(OH)D deficiency,
      suggesting that low levels of serum 25(OH)D was related to AITD. 

PMID- 25854836
TI  - Psychosocial Risk Factors and Musculoskeletal Symptoms among White and Blue
      collar Workers at Private and Public Sectors.
AB  - OBJECTIVES: The aim of this study was to evaluate musculoskeletal and
      psychosocial perception and compare these conditions regarding the type of job
      (white or blue-collar) and the type of management model (private or public).
      METHODS: Forty-seven public white-collar (PuWC), 84 private white-collar (PrWC)
      and 83 blue-collar workers (PrBC) were evaluated. Job Content Questionnaire (JCQ)
      and Utrecht Work Engagement Scale (UWES) were applied to evaluate psychosocial
      factors. Nordic Musculoskeletal Questionnaire (NMQ) was used to assess
      musculoskeletal symptoms. Pressure Pain Threshold (PPT) was measured to evaluate
      sensory responses. RESULTS: According to JCQ, all groups were classified as
      active profile. There was a significant association between work engagement and
      workers' categories (p < 0.05). PrWC workers had the highest scores for all the
      UWES domains, while PrBC had the lowest ones. PPT showed that PrBC workers had an
      increased sensitivity for left deltoid (p < 0.01), and for both epicondyles (p <
      0.01), when compared to the other groups. PrWC workers had an increased
      sensitivity for both epicondyles than PuWC (right p < 0.01; left, p = 0.05).
      There was no significant association in the report of symptoms across the groups
      (p > 0.05). CONCLUSION: This study showed differences in psychosocial risk
      factors and musculoskeletal symptoms in workers engaged in different types of
      jobs and work organization. Personal and work-related characteristics,
      psychosocial factors and PPT responses were different across workers' group.
      Despite all, there was no significant difference in reported symptoms across the
      groups, possibly indicating that the physical load is similar among the sectors.

PMID- 25854838
TI  - Larvicidal activity of the essential oil of Youngia japonica aerial parts and its
      constituents against Aedes albopictus.
AB  - The aim of this study was to evaluate the larvicidal activity of the essential
      oil of Youngia japonica aerial parts against the larvae of Aedes albopictus and
      to isolate any active compounds from the oil. Gas chromatography-mass
      spectrometry (GC-MS) analyses revealed the presence of 31 compounds, with menthol
      (23.53%), alpha-asarone (21.54%), 1,8-cineole (5.36%), and caryophyllene (4.45%)
      as the major constituents. Bioactivity-directed chromatographic separation of the
      oil led to the isolation of menthol and alpha-asarone as active compounds. The
      essential oil of Y. japonica exhibited larvicidal activity against the fourth
      instar larvae of A. albopictus with an LC50 value of 32.45 MUg/mL. alpha-Asarone
      and menthol possessed larvicidal activity against the fourth instar larvae of A.
      albopictus with LC50 values of 24.56 MUg/mL and 77.97 MUg/mL, respectively. The
      results indicate that the essential oil of Y. japonica aerial parts and the two
      constituents can be potential sources of natural larvicides.

PMID- 25854837
TI  - Set-based tests for genetic association in longitudinal studies.
AB  - Genetic association studies with longitudinal markers of chronic diseases (e.g.,
      blood pressure, body mass index) provide a valuable opportunity to explore how
      genetic variants affect traits over time by utilizing the full trajectory of
      longitudinal outcomes. Since these traits are likely influenced by the joint
      effect of multiple variants in a gene, a joint analysis of these variants
      considering linkage disequilibrium (LD) may help to explain additional phenotypic
      variation. In this article, we propose a longitudinal genetic random field model
      (LGRF), to test the association between a phenotype measured repeatedly during
      the course of an observational study and a set of genetic variants. Generalized
      score type tests are developed, which we show are robust to misspecification of
      within-subject correlation, a feature that is desirable for longitudinal
      analysis. In addition, a joint test incorporating gene-time interaction is
      further proposed. Computational advancement is made for scalable implementation
      of the proposed methods in large-scale genome-wide association studies (GWAS).
      The proposed methods are evaluated through extensive simulation studies and
      illustrated using data from the Multi-Ethnic Study of Atherosclerosis (MESA). Our
      simulation results indicate substantial gain in power using LGRF when compared
      with two commonly used existing alternatives: (i) single marker tests using
      longitudinal outcome and (ii) existing gene-based tests using the average value
      of repeated measurements as the outcome. 

PMID- 25854839
TI  - Antiviral and antitumor activities of the lectin extracted from Aspidistra
      elatior.
AB  - Lectins, a group of highly diverse proteins of non-immune origin and are
      ubiquitously distributed in plants, animals and fungi, have multiple significant
      biological functions, such as anti-fungal, anti-viral and, most notably, anti
      tumor activities. A lectin was purified from the rhizomes of Aspidistra elatior
      Blume, named A. elatior lectin (AEL). In vitro experiments showed that the
      minimum inhibitory concentrations of AEL against the vesicular stomatitis virus,
      Coxsackie virus B4, and respiratory syncytial virus were all the same at about 4
      MUg/mL. However, AEL was ineffective against the Sindbis virus and reovirus-1.
      AEL also showed significant in vitro antiproliferative activity towards Bre-04,
      Lu-04, HepG2, and Pro-01 tumor cell lines by increasing the proportion of their
      sub-G1 phase. However, AEL failed to restrict the proliferation of the HeLa cell
      line. Western blotting indicated that AEL induced the upregulation of cell cycle
      related proteins p53 and p21. The molecular basis and species-specific
      effectiveness of the anti-proliferative and anti-viral potential of AEL are
      discussed. 

PMID- 25854840
TI  - Susceptibility of Microsporum canis arthrospores to a mixture of chemically
      defined essential oils: a perspective for environmental decontamination.
AB  - The zoophilic dermatophyte Microsporum canis has cats as natural reservoir, but
      it is able to infect a wide range of hosts, including humans, where different
      clinical features of the so-called ringworm dermatophytosis have been described.
      Human infections are increasingly been reported in Mediterranean countries. A
      reliable control program against M. canis infection in cats should include an
      antifungal treatment of both the infected animals and their living environment.
      In this article, a herbal mixture composed of chemically defined essential oils
      (EOs) of Litsea cubeba (1%), Illicium verum, Foeniculum vulgare, and Pelargonium
      graveolens (0.5% each) was formulated and its antifungal activity assessed
      against M. canis arthrospores which represent the infective environmental stage
      of M. canis. Single compounds present in higher amounts in the mixture were also
      separately tested in vitro. Litsea cubeba and P. graveolens EOs were most
      effective (minimum inhibitory concentration (MIC) 0.5%), followed by EOs of I.
      verum (MIC 2%) and F. vulgare (MIC 2.5%). Minimum fungicidal concentrations (MFC)
      values were 0.75% (L. cubeba), 1.5% (P. graveolens), 2.5% (I. verum) and 3% (F.
      vulgare). MIC and MFC values of the mixture were 0.25% and 0.5%, respectively.
      The daily spray of the mixture (200 MUL) directly onto infected hairs inhibited
      fungal growth from the fourth day onwards. The compounds present in higher
      amounts exhibited variable antimycotic activity, with MIC values ranging from
      >10% (limonene) to 0.1% (geranial and neral). Thus, the mixture showed a good
      antifungal activity against arthrospores present in infected hairs. These results
      are promising for a further application of the mixture as an alternative tool or
      as an adjuvant in the environmental control of feline microsporosis. 

PMID- 25854842
TI  - Acylated flavonol diglucosides from Ammania auriculata.
AB  - Chemical investigation of the extract of the whole Ammania auriculata plant
      resulted in the identification of 13 polyphenols, including the hitherto unknown
      flavonoids, kaempferol 3-O-beta-(6"-galloylglucopyranoside)-7-O-beta
      glucopyranoside, and its quercetin analogue. The structures of all isolates were
      elucidated by conventional methods, spectroscopic analysis, including 1D and 2D
      NMR, and by HRESI-MS as well. 

PMID- 25854841
TI  - Three further triterpenoid saponins from Gleditsia caspica fruits and protective
      effect of the total saponin fraction on cyclophosphamide-induced genotoxicity in
      mice.
AB  - Three triterpenoidal saponins were isolated from the saponin fraction derived
      from a Gleditsia caspica Desf. methanolic fruit extract. The isolated saponins
      were identified as gleditsiosides B, C, and Q based on spectral data. The saponin
      containing fraction was evaluated in vivo for genotoxic and antigenotoxic
      activities. The fraction caused no DNA damage in Swiss albino male mice treated
      with a dose of 45 mg/kg body weight for 24 h, although it significantly inhibited
      the number of chromosomal aberrations induced by cyclophosphamide (CP) in bone
      marrow and germ cells when applied before or after CP administration. The
      inhibitory indices in chromosomal aberrations were 59% and 41% for bone marrow
      and 48% and 43% for germ cells, respectively. In addition, the saponin fraction
      was found to reduce the viability of the human tumor cell line MCF-7 in a dose
      dependent manner with an extrapolated IC50 value in the range of 220 MUg/mL. 

PMID- 25854843
TI  - Synthesis and antimicrobial properties of N-substituted derivatives of (E)-2',3"
      thiazachalcones.
AB  - N-alkyl substituted 2',3"-thiazachalcones {3-[(1E)-3-(4-methylthiophene-2-yl)-3
      oxoprop-1-en-1-yl]-1-alkyl (C5-12,14) pyridinium bromides} were synthesized by a
      two-step reaction. The newly synthesized compounds were characterized by IR, 1H
      NMR, 13C NMR, elemental analysis and mass spectral studies. The synthesized
      compounds were tested for antibacterial activities and found to be more active
      against Gram-positive as compared to Gram-negative bacteria. 

PMID- 25854845
TI  - Percutaneous Re-positioning of Dislocated Port-Catheters in Patients with
      Dysfunctional Central-Vein Port-Systems.
AB  - PURPOSE: Observational analysis of percutaneous repositioning of displaced port
      catheters in patients with dysfunctional central-venous port-systems. METHODS: A
      total of 1061 patients with dysfunctional venous pectoral port-systems were
      referred for port-angiography. Dislocated port-catheters were identified in 37
      (3.5 %) patients (11 males, mean age 58.1 +/- 7.2 [range 48-69] years; 26
      females, 57.0 +/- 13.5 [range 24-75] years) 3.9 +/- 6.6 months (range 1 day-26
      months) after port-implantation. Percutaneous repositioning in all patients was
      performed by transfemoral catheter maneuvers, snaring, or wire-assisted long-loop
      snaring. Primary endpoint was successful repositioning. Safety endpoints included
      port-damage or procedure-related complications. Follow-up encompassed routine
      clinical and radiological controls, including chest X-ray or computed tomography
      for 12.9 +/- 17.9 (range 1-81) months. RESULTS: Clinical signs of port
      dysfunction due to dislocation of port-catheters included difficult aspiration in
      23 (62.2 %), resistance or inability to inject in 17 (46.0 %), and pain during
      injection in 2 (5.4 %) patients. Primary technical success for repositioning
      displaced port-catheters was 97.3 % (36/37 patients). In 1 (2.7 %) patient,
      repositioning failed due to complete embedding of the port-catheter in an
      extensive chronic jugular vein thrombosis (Paget-von-Schroetter syndrome) that
      prevented endovascular access to the port-catheter. Redisplacement occurred after
      initial successful repositioning: immediately in two patients due to a too short
      port-catheter (two-tailed Fisher's exact-test, p = 0.0101), and in two patients
      with appropriate catheter-length after 5, resp. 7 months. No procedure-associated
      complications, e.g., port-catheter disconnection or disruption, occurred.
      CONCLUSIONS: Repositioning of dysfunctional displaced central-venous port
      catheters with appropriate catheter-length is safe and effective. Even
      challenging conditions, e.g., wall-adherent port-catheter tip or a thrombosed
      catheter-bearing vein are feasible. Repositioning of too short port-catheters is
      ineffective.

PMID- 25854844
TI  - Pediatric Thyroid Microcarcinoma.
AB  - BACKGROUND: Thyroid microcarcinomas (TMCs) are increasing in the general
      population, most commonly in older individuals; however, the incidence,
      characteristics, and outcomes of TMCs in pediatric patients has not been studied.
      METHODS: All patients <=19 years of age with differentiated thyroid carcinoma
      (DTC) were identified from the surveillance, epidemiology, and end results
      registry from 1988 to 2009. Patients were divided into two groups based on tumor
      siz e: TMCs (<=1 cm) and tumors >1 cm. Demographic, tumor, and treatment
      characteristics, as well as overall survival (OS) and disease-specific survival
      (DSS), were compared between the two groups. The TMC group was analyzed
      separately for predictors of overall and disease-specific death. RESULTS: Of 1825
      pediatric DTC patients, 8.4 % had a TMC, and, over the past decade, the incidence
      has decreased (6.5 vs 14.5 %; p < 0.001). Compared to patients with DTCs >1 cm,
      TMCs were more likely to have papillary histology, negative lymph nodes, be
      treated with a partial thyroidectomy [odds ratio (OR) 3.46, CI 2.02-5.93] and not
      receive radioiodine (OR 1.77, CI 1.10-2.83). Neither OS (TMC: 253.59 months; DTC
      >1 cm: 257.97 months) nor DSS (TMC: 256.38 months; DTC >1 cm: 260.77 months)
      differed between groups. Predictors of decreased OS in the entire cohort included
      secondary malignancy status (p = 0.001), black race (p = 0.006) and follicular or
      Hurthle histology (p = 0.001). In patients with primary TMC, only follicular or
      Hurthle histology (p = 0.001) predicted decreased OS. CONCLUSIONS: TMCs in
      patients <=19 years of age are declining and comprise <10 % of pediatric thyroid
      malignancies. TMCs are most commonly treated with a partial thyroidectomy not
      followed by radioiodine, and have an excellent OS and DSS.

PMID- 25854846
TI  - Visible light-driven efficient overall water splitting using p-type metal-nitride
      nanowire arrays.
AB  - Solar water splitting for hydrogen generation can be a potential source of
      renewable energy for the future. Here we show that efficient and stable
      stoichiometric dissociation of water into hydrogen and oxygen can be achieved
      under visible light by eradicating the potential barrier on nonpolar surfaces of
      indium gallium nitride nanowires through controlled p-type dopant incorporation.
      An apparent quantum efficiency of ~12.3% is achieved for overall neutral (pH~7.0)
      water splitting under visible light illumination (400-475 nm). Moreover, using a
      double-band p-type gallium nitride/indium gallium nitride nanowire
      heterostructure, we show a solar-to-hydrogen conversion efficiency of ~1.8% under
      concentrated sunlight. The dominant effect of near-surface band structure in
      transforming the photocatalytic performance is elucidated. The stability and
      efficiency of this recyclable, wafer-level nanoscale metal-nitride photocatalyst
      in neutral water demonstrates their potential use for large-scale solar-fuel
      conversion. 

PMID- 25854847
TI  - Critical Congenital Heart Diseases in Preterm Neonates: Is Early Cardiac Surgery
      Quite Reasonable?
AB  - Prematurity is a recognized risk factor for morbidity and mortality following
      cardiac surgery. Postoperative and long-term outcomes after cardiac surgery
      performed in the preterm period are poorly described. The aim of this study was
      to analyze a population of preterm neonates operated on for critical congenital
      heart disease (CHD) before 37 weeks of gestational age (wGA) with special
      attention given to early and late mortality and morbidity. Between 2000 and 2013,
      28 preterm neonates (median gestational age (GA) 34.3 weeks) underwent
      cardiopulmonary bypass (CPB) surgery for critical CHD before 37 wGA; records were
      retrospectively reviewed. All patients except three with single ventricle
      physiology had a single-stage anatomic repair. Overall mortality was 43 % (95 %
      CI 25-62). Risk factors for death were birth weight (p = 0.032) and weight at
      surgery (p = 0.037), independently of GA, preoperative status, CPB and aortic
      clamp time. Seven patients, including those with univentricular hearts, died
      during the postoperative period, and five in the first year after surgery. Median
      follow-up was 5.9 years (range 1 month-12.8 years). Kaplan-Meier survival rate
      was 75 % (95 % CI 59-91) at 1 month, and 57 % (95 % CI 39-75) at 1 and 5 years.
      Eight patients required reoperations after a delay of 2.8 +/- 1.3 months; eight
      had bronchopulmonary dysplasia. At the end of follow-up, nine patients were
      asymptomatic. One-stage biventricular repair for critical CHD on preterm neonates
      was feasible. Mortality remained high but acceptable, mainly confined to the
      first postoperative year and related to small weight. Despite reoperations, long
      term clinical status was good in most survivors. Further long-term prospective
      investigations are necessary to evaluate neurodevelopmental outcomes.

PMID- 25854848
TI  - Biventricular Badness: Rare Images of Ebstein Anomaly of the Tricuspid Valve in a
      Patient with Hypoplastic Left Heart Syndrome.
AB  - We report a rare case of hypoplastic left heart syndrome coexisting in a patient
      with Ebstein anomaly of the tricuspid valve, which has previously been described
      only in pathological studies. A fetal echocardiogram at 27-weeks gestation showed
      severe aortic stenosis with evolving hypoplastic left heart syndrome, significant
      endocardial fibroelastosis, a dysplastic tricuspid valve with moderate
      regurgitation, right atrial and ventricular dilation, and signs of fetal
      congestive heart failure. Due to inadequate left heart size, the patient was not
      a candidate for fetal intervention for critical aortic stenosis, and repeat
      studies showed progression of the lesion through the pregnancy. The infant was
      delivered at 36-weeks gestation with signs of hydrops, and a postnatal
      echocardiogram confirmed hypoplastic left heart syndrome as well as severe
      Ebstein anomaly of the tricuspid valve. The infant did not survive to
      intervention.

PMID- 25854849
TI  - Bioadhesive hydrogels for cosmetic applications.
AB  - INTRODUCTION: The use of bioadhesive hydrogels for skin care presents important
      advantages such as long residence times on the application site and reduced
      product administration frequency. OBJECT: The aim of the present work was to
      develop bioadhesive hydrogels for skin application, using caffeine as a model
      active ingredient. METHODS: Eight hydrogels were formulated using binary
      combinations of a primary polymer (carbomer homopolymer type C (Carbopol((r))
      980) or kappa carrageenan potassium salt (Gelcarin((r)) GP-812 NF)) and a
      secondary polymer (carbomer copolymer type B (Pemulen(TM) TR-1), xanthan gum or
      guar gum). Hydrogels were characterized by means of physico-chemical (dynamic
      rheological measurements, spreadability and adhesion measurements) and sensory
      methods (projective mapping in combination with a check-all-that-apply (CATA)
      question). Caffeine hydrogels were formulated using two of the most promising
      formulations regarding adhesion properties and sensory characteristics. In vitro
      active ingredient release studies were carried out. RESULTS: Hydrogel
      formulations showed a prevalently elastic rheological behaviour. Complex
      viscosity of carbomer homopolymer type C hydrogels was higher than that of the
      kappa carrageenan hydrogels. Besides, complex viscosity values were dependent on
      the secondary polymer present in the formulation. Significant differences among
      hydrogels were found in detachment force, work of adhesion and spreading diameter
      results. Association of projective mapping with CATA allowed to determine
      similarities and dissimilarities among samples. Cluster analysis associated the
      samples in two groups. Two hydrogels were selected to study the release of
      caffeine. Both hydrogels presented similar release profiles which were well
      described by the Higuchi model. Caffeine release was exclusively controlled by a
      diffusive process. CONCLUSION: Physico-chemical and sensory techniques enabled
      the identification of bioadhesive hydrogel formulations with positive
      characteristics for cosmetic applications. Formulations which combined carbomer
      homopolymer type C with xanthan gum or with carbomer copolymer type B were the
      most promising for bioadhesive skin products. Caffeine release profiles of
      selected formulations were not statistically different. Both hydrogels gradually
      released the active ingredient, reaching approximately 80% within the first 5 h,
      and their profiles were well described by the Higuchi model. In this context, it
      could be concluded that the selected hydrogels are suitable bioadhesive hydrogel
      formulations for cosmetic application on the skin.

PMID- 25854851
TI  - Regression of Walker 256 carcinosarcoma in vasopressin-deficient Brattleboro rats
      is accompanied by a changed laminin pattern.
AB  - Walker 256 carcinosarcoma is a transplantable model of rat carcinoma that
      originally appeared spontaneously in mammary glands. The growth rate of Walker
      256 carcinosarcoma in vasopressin-deficient Brattleboro rats is lower than in WAG
      rats and their congenic hybrids with normal vasopressin levels. Study of tumor
      proteins detected essential alterations. Tumor regression starting at the 14th
      day in Brattleboro rats was accompanied by changes in the laminin pattern. At the
      21st day, the concentration of alpha-chains became twice as low, while beta
      chains of laminin showed a sixfold increase compared to the initial equimolar
      correlation of bands. Congenic hybrids having one active copy of the vasopressin
      gene to provide a physiological level of hormone against the genetic background
      of Brattleboro rats show the same laminin alterations as WAG rats. They
      demonstrated a similar moderate increase of gamma-chains and threefold growth of
      alpha- and beta-chains of laminin in tumor tissue. It is supposed that
      vasopressin may be involved in the regulation of relevant local stimuli to
      trigger renovation of the laminin composition in a course of growing Walker 256
      carcinosarcoma. 

PMID- 25854852
TI  - Genetic Population Structure of Thunnus albacares in the Central Pacific Ocean
      Based on mtDNA COI Gene Sequences.
AB  - Thunnus albacares is an important fishery species throughout the world.
      Polymorphisms of sequence variations in mtDNA COI genes were assessed to explore
      the genetic differentiations among 11 populations of T. albacares sampled from
      the central Pacific Ocean. Sixty-one mtDNA haplotypes and 38 variable sites were
      detected. Analysis of mtDNA COI sequences revealed that tuna from the 11
      localities were characterized by moderately high haplotype diversity (h = 0.650
      +/- 0.040), while sequence divergence between haplotypes was relatively low (pi =
      0.00364 +/- 0.00044). Analyses of molecular variance and FST analysis supported
      that significant genetic differentiations existed between some of the sampled
      populations. Tests of neutral evolution and mismatch distribution analysis
      suggested that T. albacares might have experienced a population expansion, which
      possibly occurred within the last 0.82 million years. Our study unraveled the
      genetic structure of the extant population of T. albacares and addressed the
      related fishery management issues including fishery stock identification and
      management.

PMID- 25854853
TI  - SNP Variants in RET and PAX2 and Their Possible Contribution to the Primary
      Hyperoxaluria Type 1 Phenotype.
AB  - Primary hyperoxaluria type 1 (PH1) is a rare genetic kidney disease caused by a
      deficiency of alanine:glyoxylate aminotransferase (AGT). Genetic heterogeneity of
      the AGT gene cannot fully account for heterogeneity in the clinical phenotype.
      This study investigates a possible contribution to the clinical phenotype from
      SNPs in RET or PAX2 genes associated with reduced nephron number. The frequencies
      of these SNPs were compared in PH1-affected DNA samples and normal controls, and
      relative to age of onset in PH1-affected individuals. The frequencies of the risk
      alleles were higher with early age of onset, although not significantly so.
      However, homozygosity for the risk alleles of RET and PAX2 was not seen in the
      late onset group. The overall frequencies of risk alleles and the numbers of
      homozygotes were significantly higher for PAX2 in PH1 samples versus controls,
      suggestive of a bias towards more severe clinical phenotypes in the PH1 samples
      submitted for analysis. 

PMID- 25854854
TI  - Rapid screening and identification of active ingredients in licorice extract
      interacting with V3 loop region of HIV-1 gp120 using ACE and CE-MS.
AB  - The binding of envelope protein gp120 to glycosphingolipids is very important
      during the human immunodeficiency virus entering into the host cell. This step
      occurs in the V3 loop region in particularly. The conserved core sequence of V3
      loop in gp120 was named R15K. Anti-HIV drug targeting to R15K would avoid the
      drug-resistance caused by HIV-1 genetic diversity. Here, for the first time,
      affinity capillary electrophoresis (ACE) and capillary electrophoresis-mass
      spectrometry (CE-MS) were used for establishing a simple, rapid and effective
      method of screening the licorice extract for biological activity (anti-HIV),
      which avoided the complicated isolation and purification process. R15K, 3'
      sialyllactose (the positive control), and d-galactose (the negative control) were
      used for the development and validation of ACE method. After the interaction
      between licorice extract and R15K was confirmed by ACE, the relative active
      ingredients were isolated by SPE and their structures were determined by CE-ESI
      MS online. In this research, two mixtures from licorice extract were found to be
      active. Furthermore, glycyrrhizin and licorice saponin G2 were verified as the
      main ingredients that significantly interacted with R15K via CE-MS and LC-MS. The
      results of quantitative assays showed that the active mixture contained
      glycyrrhizin of 74.23% and licorice saponin G2 of 9.52%. Calculated by Scatchard
      analysis method, glycyrrhizin/R15K complex had the highest binding constant (1.69
      +/- 0.08) * 10(7)L/mol among 27 compounds isolated from licorice extract. The
      anti-HIV activity of glycyrrhizin was further confirmed by bioactive experiment
      of cellular level. This strategy might provide a high throughput screening and
      identifying platform for seeking HIV-1 inhibitors in natural products.

PMID- 25854855
TI  - LC-MS/MS method for the determination of rosiglitazone on rat dried blood spots
      and rat urine: Application to pharmacokinetics.
AB  - A bioanalytical method for the quantification of rosiglitazone on rat dried blood
      spots (DBS) and rat urine using liquid chromatography, electrospray ionization
      coupled with tandem mass spectrometry (LC-ESI-MS/MS) was developed and validated.
      The chromatographic separation was achieved on a Nova-Pak C18 Column (150 mm *
      4.6 mm i.d., 4 MUm), using 30 mM ammonium acetate (pH 4.0 adjusted with acetic
      acid) and acetonitrile (75:25, v/v) as a mobile phase at ambient temperature. LC
      MS detection was performed with selected ion monitoring using target ions at m/z
      358 and m/z 356 for rosiglitazone and pioglitazone respectively. The calibration
      curve showed a good linearity in the concentration range of 0.05-100 ng/mL. The
      effect of hematocrit, blood volume and punch location for DBS samples was
      studied. The mean recoveries of rosiglitazone from DBS and urine were 93.30% and
      92.49% respectively. The intra and inter-day precisions of RSD were less than
      4.82% in DBS as well as urine. The limit of detections and quantifications were
      0.015 and 0.052 ng/mL in DBS and 0.023 and 0.075 ng/mL in urine samples
      respectively. The method was validated as per FDA guidelines and successfully
      applied to a pharmacokinetic study of rosiglitazone in rats.

PMID- 25854856
TI  - Physicochemical and crystal structure analysis of pranlukast pseudo-polymorphs
      II: Solvate and cocrystal.
AB  - Pranlukast (PRS) is a leukotriene receptor antagonist for the treatment of
      bronchial asthma. In this study, six new solvates and one new cocrystal of PRS
      were characterized by PXRD, TG-DTA, DSC, vapor sorption analysis and the
      dissolution test. In addition, the crystal structures were determined by single
      crystal X-ray structure analysis. PRS was found to be a rare example of a
      promiscuous multicomponent crystal former. The crystal packing patterns of these
      crystals can be categorized into the sheet-like and channel-like patterns. The
      ethanol solvate (PRS/ethanol) and urea cocrystal (PRS/urea) were more stable than
      the others under humid conditions. PRS/ethanol showed an improved dissolution
      profile compared to PRS HH and PRS/urea. 

PMID- 25854857
TI  - Differentiation of salivary bacterial profiles of subjects with periodontitis and
      dental caries.
AB  - Bacterial profiles of saliva in subjects with periodontitis and dental caries
      have been demonstrated to differ from that of oral health. The aim of this
      comparative analysis of existing data generated by the Human Oral Microbe
      Identification Microarray (HOMIM) from 293 stimulated saliva samples was to
      compare bacterial profiles of saliva in subjects with periodontitis and dental
      caries. 

PMID- 25854858
TI  - Electrochemical driven water oxidation by molecular catalysts in situ polymerized
      on the surface of graphite carbon electrode.
AB  - A simple strategy to immobilize highly efficient ruthenium based molecular water
      oxidation catalysts on the basal-plane pyrolytic graphite electrode (BPG) by
      polymerization has been demonstrated. The electrode 1@BPG has obtained a high
      initial turnover frequency (TOF) of 10.47 s(-1) at ~700 mV overpotential, and a
      high turnover number (TON) up to 31600 in 1 h electrolysis. 

PMID- 25854859
TI  - Pharmacokinetics, pharmacodynamics, safety, and tolerability of pradigastat, a
      novel diacylglycerol acyltransferase 1 inhibitor in overweight or obese, but
      otherwise healthy human subjects.
AB  - Pradigastat is a potent and selective inhibitor of diacylglycerol acyltransferase
      1, an enzyme highly expressed in the small intestine that plays a key role in
      postprandial triglyceride synthesis. This first-in-human study evaluated the
      pharmacokinetics, pharmacodynamics, safety, and tolerability of pradigastat
      administered at single and multiple doses in overweight or obese healthy
      subjects. In single-dose cohorts (n = 72), subjects were randomized sequentially
      to receive single doses of pradigastat (1, 3, 10, 30, 100, or 300 mg) or placebo
      under fasted condition and prior to breakfast. In multiple-dose cohorts (n =
      106), subjects were randomized to receive pradigastat (1, 5, 10, or 25 mg) or
      placebo prior to breakfast for 14 days. Following a single oral dosing,
      pradigastat was absorbed slowly, with a median tmax of ~10 hours and eliminated
      slowly with a long half-life. With multiple oral doses, a 10- to 17-fold higher
      systemic exposure was observed. Pradigastat treatment (single and multiple doses)
      led to dose-dependent suppression of postprandial triglyceride excursions over 9
      hours following a high-fat meal test. In addition, pradigastat suppressed
      postprandial glucose and insulin and increased plasma glucagon-like peptide-1
      levels. Overall, pradigastat was safe and tolerated at single and multiple doses
      in healthy subjects.

PMID- 25854860
TI  - Obesity status transitions across the elementary years: use of Markov chain
      modelling.
AB  - OBJECTIVE: The objective of this study was to assess overweight and obesity
      status transition probabilities using first-order Markov transition models
      applied to elementary school children. METHOD: Complete longitudinal data across
      11 assessments were available from 1494 elementary school children (from 7599
      students in 41 out of 45 schools in a Southeast Texas school district) from
      kindergarten to the beginning of the fifth grade. Heights and weights were
      measured by trained school nurses using standard procedures at the beginning and
      end of each school year for the 11 consecutive assessments. To estimate the
      transition probabilities, first-order three-state (healthy weight, overweight and
      obese) Markov transition models were fit to the longitudinal weight status data
      of all assessment periods. RESULTS: While there was a gradual shift to more
      children in the overweight or obese category over 5 years, children were most
      likely to stay in the same weight category as the previous assessment. A
      consistent seasonal difference in the probability of changing weight status
      category was seen, with a greater probability of becoming overweight and obese
      during the summer compared with the school year. The transition probabilities to
      obesity were higher among boys, Hispanic and non-Hispanic Black, and lower
      socioeconomic status children. CONCLUSIONS: This study provides the first
      application of a Markov transition model to child weight status data. The
      transitions into the overweight and obese categories were small, but persistent,
      with smaller percentages transitioning out of overweight or obese. Early
      monitoring and summer intervention strategies are needed to prevent the slow, but
      relentless, transition into the overweight and obese categories.

PMID- 25854861
TI  - Administration of fenoldopam in critically ill small animal patients with acute
      kidney injury: 28 dogs and 34 cats (2008-2012).
AB  - OBJECTIVE: To describe the clinical features and outcomes of critically ill dogs
      and cats with acute kidney injury (AKI) receiving fenoldopam infusions compared
      to patients with AKI that did not receive fenoldopam. DESIGN: Retrospective
      clinical study from May 1, 2008 until June 1, 2012. SETTING: Private emergency
      and specialty referral hospital. ANIMALS: Client-owned dogs (28) and cats (34)
      with AKI that received fenoldopam compared with similar patients with AKI (30
      dogs and 30 cats) that did not. INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: The medical records of 62 critically ill dogs and cats with AKI that
      received fenoldopam were reviewed. Presenting clinical signs, physical
      examination findings, and primary and secondary disease processes were identified
      in all patients. The mean number of days on fenoldopam was 1.5 days (range 0.3
      4.0 days) for dogs and 1.9 days (range 1.0-4.0 days) for cats. Eleven of 28 (39%)
      dogs survived to discharge and 13 of 34 (38%) of the cats survived to discharge.
      Of the animals in the group receiving fenoldopam that died, the majority (84%)
      were euthanized. Potential adverse reactions were evaluated, with hypotension
      being the most commonly encountered adverse effect (7% of fenoldopam group [FG]
      dogs and 23% of FG cats). When compared with patients with AKI that did not
      receive fenoldopam, no significant differences were found between the groups with
      regards to survival, length of hospital stay, adverse effects, or changes in
      creatinine, BUN, or sodium concentrations except that patients receiving
      fenoldopam were significantly more likely to have received other renally active
      medications. CONCLUSIONS: In this study of patients with AKI, fenoldopam
      administration at 0.8 MUg/kg/min in dogs and 0.5 MUg/kg/min in cats appeared
      relatively safe but was not associated with improvement in survival to discharge,
      length of hospital stay, or improvement in renal biochemical parameters when
      compared to patients with AKI not receiving fenoldopam.

PMID- 25854862
TI  - Effect of six fluoroquinolones on the expression of four efflux pumps in the
      multidrug resistant Escherichia coli isolates.
AB  - In this study, a total of 78 Escherichia coli clinical isolates were isolated
      from canines diagnosed with urinary tract infections. 23/78 isolates (29.5 %)
      showed multidrug resistance (MDR) phenotype, including the isolates both
      susceptible to fluoroquinolones (FQs) (FQ(S)-MDR, n = 12) and resistant to FQs
      (FQ(R)-MDR, n = 11). For these MDR isolates, mutations within quinolone
      resistance determining region of gyrA and parC were determined by PCR
      amplification and DNA sequencing. The relative quantification of emrE, acrB,
      macB, and mdfA genes expression in MDR isolates was determined by quantitative
      real-time PCR before and after exposure to the FQs (10 ug/ml). The results showed
      that a temporary exposure to FQs could lead to various degrees of up or down
      regulation on the expression of four efflux pumps in MDR isolates depending on
      the resistant phenotype and the activities of the FQs. Generally, the FQ(R)-MDR
      isolates showed more obvious changes in average expression levels of these
      transporters versus the FQ(S)-MDR isolates, with a largest increase in emrE, and
      followed by acrB, while the expression of macB and mdfA did not change as
      radically. Meanwhile, there is a reverse relationship between the expression
      changes and the activities of the FQs tested. The expression was higher in the
      isolates exposed to enrofloxacin, ciprofloxacin, and orbifloxacin, and followed
      by the marbofloxacin, gatifloxacin, and pradofloxacin, and the average expression
      levels of some efflux pumps even decreased as the isolates were exposed to
      gatifloxacin or pradofloxacin.

PMID- 25854863
TI  - Enhancing the Predictive Power of Mutations in the C-Terminus of the KCNQ1
      Encoded Kv7.1 Voltage-Gated Potassium Channel.
AB  - Despite the overrepresentation of Kv7.1 mutations among patients with a robust
      diagnosis of long QT syndrome (LQTS), a background rate of innocuous Kv7.1
      missense variants observed in healthy controls creates ambiguity in the
      interpretation of LQTS genetic test results. A recent study showed that the
      probability of pathogenicity for rare missense mutations depends in part on the
      topological location of the variant in Kv7.1's various structure-function
      domains. Since the Kv7.1's C-terminus accounts for nearly 50 % of the overall
      protein and nearly 50 % of the overall background rate of rare variants falls
      within the C-terminus, further enhancement in mutation calling may provide
      guidance in distinguishing pathogenic long QT syndrome type 1 (LQT1)-causing
      mutations from rare non-disease-causing variants in the Kv7.1's C-terminus.
      Therefore, we have used conservation analysis and a large case-control study to
      generate topology-based estimative predictive values to aid in interpretation,
      identifying three regions of high conservation within the Kv7.1's C-terminus
      which have a high probability of LQT1 pathogenicity. 

PMID- 25854864
TI  - Interaction between human BAP31 and respiratory syncytial virus small hydrophobic
      (SH) protein.
AB  - The small hydrophobic (SH) protein is a short channel-forming polypeptide encoded
      by the human respiratory syncytial virus (hRSV). Deletion of SH protein leads to
      the viral attenuation in mice and primates, and delayed apoptosis in infected
      cells. We have used a membrane-based yeast two-hybrid system (MbY2H) and a
      library from human lung cDNA to detect proteins that bind SH protein. This led to
      the identification of a membrane protein, B-cell associated protein 31 (BAP31).
      Transfected SH protein co-localizes with transfected BAP31 in cells, and pulls
      down endogenous BAP31. Titration of purified C-terminal endodomain of BAP31
      against isotopically labeled SH protein in detergent micelles suggests direct
      interaction between the two proteins. Given the key role of BAP31 in protein
      trafficking and its critical involvement in pro- and anti-apoptotic pathways,
      this novel interaction may constitute a potential drug target. 

PMID- 25854865
TI  - The full-length genome sequences of nine HCV genotype 4 variants representing a
      new subtype 4s and eight unclassified lineages.
AB  - We characterized the full-length genomes for nine novel variants of HCV genotype
      4 (HCV-4), representing a new subtype 4s and eight unclassified lineages. They
      were obtained from patients who resided in Canada but all had origins in Africa.
      An extended maximum clade credibility (MCC) tree was reconstructed after the
      inclusion of 30 reference sequences. It differentiated 18 assigned subtypes and
      10 unclassified lineages within HCV-4. Similar analysis of 102 partial NS5B
      sequences resulted in another MCC tree that revealed 22 assigned subtypes (4a-4t,
      4w, and 4v) and 30 unclassified lineages at the subtype level. Our study shows
      that HCV-4 is taxonomically complex and it displays high genetic diversity to
      support an African origin. 

PMID- 25854866
TI  - Brain death declaration: Practices and perceptions worldwide.
AB  - OBJECTIVE: To assess the practices and perceptions of brain death determination
      worldwide and analyze the extent and nature of variations among countries.
      METHODS: An electronic survey was distributed globally to physicians with
      expertise in neurocritical care, neurology, or related disciplines who would
      encounter patients at risk of brain death. RESULTS: Most countries (n = 91,
      response rate 76%) reported a legal provision (n = 63, 70%) and an institutional
      protocol (n = 70, 77%) for brain death. Institutional protocols were less common
      in lower-income countries (2/9 of low [22%], 9/18 lower-middle [50%], 22/26 upper
      middle [85%], and 37/38 high-income countries [97%], p < 0.001). Countries with
      an organized transplant network were more likely to have a brain death provision
      compared with countries without one (53/64 [83%] vs 6/25 [24%], p < 0.001). Among
      institutions with a formalized brain death protocol, marked variability occurred
      in requisite examination findings (n = 37, 53% of respondents deviated from the
      American Academy of Neurology criteria), apnea testing, necessity and type of
      ancillary testing (most commonly required test: EEG [n = 37, 53%]), time to
      declaration, number and qualifications of physicians present, and criteria in
      children (distinct pediatric criteria: n = 38, 56%). CONCLUSIONS: Substantial
      differences in perceptions and practices of brain death exist worldwide. The
      identification of discrepancies, improvement of gaps in medical education, and
      formalization of protocols in lower-income countries provide first pragmatic
      steps to reconciling these variations. Whether a harmonized, uniform standard for
      brain death worldwide can be achieved remains questionable.

PMID- 25854867
TI  - Risk and protective factors for cognitive impairment in persons aged 85 years and
      older.
AB  - OBJECTIVE: To determine risk and protective factors for mild cognitive impairment
      (MCI) among persons 85 years and older. METHODS: Participants in the population
      based prospective Mayo Clinic Study of Aging were comprehensively evaluated at
      baseline and at 15 monthly intervals to determine incident MCI. At baseline,
      lifestyle factors in midlife and late life were assessed by self-reported
      questionnaire; vascular and comorbid conditions were abstracted from
      participants' medical records. RESULTS: Of 256 participants who were cognitively
      normal at enrollment (median age 87.3 years, 62% women), 121 developed MCI at a
      median 4.1 years of follow-up. Predictors of MCI were APOE epsilon4 allele
      (hazard ratio [HR] 1.89; p = 0.008), current depressive symptoms (HR 1.78; p =
      0.02), midlife onset of hypertension (HR 2.43; p = 0.005), increasing number of
      vascular diseases (HR 1.13; p = 0.02), and chronic conditions from the Charlson
      Comorbidity Index (HR 1.08; p = 0.006). Models were adjusted for sex and
      education, with age as the time variable. The risk of MCI was reduced for
      participants who reported engagement in artistic (HR 0.27; p = 0.03), craft (HR
      0.55; p = 0.02), and social (HR 0.45; p = 0.005) activities in both midlife and
      late life, and in the use of a computer in late life (HR 0.47; p = 0.008).
      CONCLUSIONS: Chronic disease burden increases risk of MCI, whereas certain
      lifestyle factors reduce risk in persons 85 years and older. This implies that
      preventive strategies for MCI may need to begin in midlife and should persist
      throughout late life.

PMID- 25854869
TI  - Comment: Is international consensus on brain death achievable?

PMID- 25854868
TI  - The brain connectome as a personalized biomarker of seizure outcomes after
      temporal lobectomy.
AB  - OBJECTIVE: We examined whether individual neuronal architecture obtained from the
      brain connectome can be used to estimate the surgical success of anterior
      temporal lobectomy (ATL) in patients with temporal lobe epilepsy (TLE). METHODS:
      We retrospectively studied 35 consecutive patients with TLE who underwent ATL.
      The structural brain connectome was reconstructed from all patients using
      presurgical diffusion MRI. Network links in patients were standardized as Z
      scores based on connectomes reconstructed from healthy controls. The topography
      of abnormalities in linkwise elements of the connectome was assessed on
      subnetworks linking ipsilateral temporal with extratemporal regions. Predictive
      models were constructed based on the individual prevalence of linkwise Z scores
      >2 and based on presurgical clinical data. RESULTS: Patients were more likely to
      achieve postsurgical seizure freedom if they exhibited fewer abnormalities within
      a subnetwork composed of the ipsilateral hippocampus, amygdala, thalamus,
      superior frontal region, lateral temporal gyri, insula, orbitofrontal cortex,
      cingulate, and lateral occipital gyrus. Seizure-free surgical outcome was
      predicted by neural architecture alone with 90% specificity (83% accuracy), and
      by neural architecture combined with clinical data with 94% specificity (88%
      accuracy). CONCLUSIONS: Individual variations in connectome topography, combined
      with presurgical clinical data, may be used as biomarkers to better estimate
      surgical outcomes in patients with TLE.

PMID- 25854870
TI  - Comment: Too much of a good thing may still be good for your brain.

PMID- 25854871
TI  - Using an email advice line to connect care for children.

PMID- 25854873
TI  - When to report adverse drug reactions in children?

PMID- 25854872
TI  - Potentially harmful excipients in neonatal medicines: a pan-European
      observational study.
AB  - OBJECTIVES: We aimed to describe administration of eight potentially harmful
      excipients of interest (EOI)-parabens, polysorbate 80, propylene glycol,
      benzoates, saccharin sodium, sorbitol, ethanol and benzalkonium chloride-to
      hospitalised neonates in Europe and to identify risk factors for exposure.
      METHODS: All medicines administered to neonates during 1 day with individual
      prescription and demographic data were registered in a web-based point prevalence
      study. Excipients were identified from the Summaries of Product Characteristics.
      Determinants of EOI administration (geographical region, gestational age (GA),
      active pharmaceutical ingredient, unit level and hospital teaching status) were
      identified using multivariable logistical regression analysis. RESULTS: Overall
      89 neonatal units from 21 countries participated. Altogether 2095 prescriptions
      for 530 products administered to 726 neonates were recorded. EOI were found in
      638 (31%) prescriptions and were administered to 456 (63%) neonates through a
      relatively small number of products (n=142; 27%). Parabens, found in 71 (13%)
      products administered to 313 (43%) neonates, were used most frequently. EOI
      administration varied by geographical region, GA and route of administration.
      Geographical region remained a significant determinant of the use of parabens,
      polysorbate 80, propylene glycol and saccharin sodium after adjustment for the
      potential covariates including anatomical therapeutic chemical class of the
      active ingredient. CONCLUSIONS: European neonates receive a number of potentially
      harmful pharmaceutical excipients. Regional differences in EOI administration
      suggest that EOI-free products are available and provide the potential for
      substitution to avoid side effects of some excipients.

PMID- 25854874
TI  - Multiple endocrine neoplasia syndromes 1 and 2: manifestations and management in
      childhood and adolescence.
AB  - The identification of the genetic causes of the multiple endocrine neoplasia
      (MEN) syndromes 1 and 2, and associated genotype-phenotype relationships, has
      revolutionised the clinical care of affected patients. A genetic diagnosis can be
      made during infancy and careful clinical surveillance, coupled with early
      intervention, has the potential to improve both morbidity and mortality. These
      developments have seen the management of patients with MEN move into the arena of
      paediatric medicine. In this review article, we consider the genetic causes of
      MEN together with the clinical manifestations and management of these syndromes. 

PMID- 25854875
TI  - Catecholamine pathway polymorphisms and antidepressant response.
AB  - INTRODUCTION: Genes that regulate the catecholamine metabolism pathways are
      potential targets for research in the antidepressant treatment response. This
      study was intended to determine whether antidepressant responses to selective
      serotonin reuptake inhibitors (SSRIs) are associated with genetic polymorphisms
      of the tyrosine or tryptophan gene in Chinese major depressive disorder (MDD)
      patients. METHODS: A total of 290 MDD patients were recruited and received a 6
      week SSRIs randomized double-blinded treatment. Allele, genotype, and haplotype
      frequencies were compared between responders and nonresponders in catecholamine
      genes. RESULTS: Genotype frequency of the rs1800544 polymorphism in the DRD4 gene
      was significantly different between responders and nonresponders after false
      discovery rate correction (P = 0.042). The frequency of the DRD4 rs1800544 CG
      genotype was significantly higher (P = 0.003) in responders (51.4%) than in
      nonresponders (35.8%), and patients with the CG genotype showed an 81.7% response
      rate. In comparison, the response rates were 73.9% and 52.2% in patients with the
      GG genotype and the CC genotype, respectively. The frequencies of the DRD4
      rs1800544 CC and GG genotypes were significantly lower (P = 0.003) in responders
      (7.7%, 40.9%) than in the nonresponders (19.4%, 44.8%). No significant difference
      was found between two groups either in genotype or allele frequencies of single
      nucleotide polymorphisms in the TPH, SLC6A2, SLC6A3, or DRD2 genes. No
      significant difference was found between two groups in TPH, SLC6A2, SLC6A3, DRD2,
      orDRD4 gene haplotypes. DISCUSSION: Polymorphisms of the DRD4 gene appear to be
      associated with SSRI treatment response in Chinese MDD patients.

PMID- 25854876
TI  - Effect of the external electric field on selected tripeptides.
AB  - The effect of external electric field (EEF) of 5.14, 25.70, and 51.40 MV/cm upon
      Cys-Asn-Ser, Glu-Arg-Leu, Glu-Cys-Glc, Ser-Asp-Leu, Ser-Glu-Met tripeptide inner
      salts was simulated involving HyperChem 8.0 software together with the AM1 method
      for optimization of the molecules' conformation. The reaction to EEF is diverse
      and specific to particular peptides. EEF stimulated an increase in the positive
      charge density on the hydrogen atoms of the N(+)H3, peptide bond NH, NH2, and
      COOH groups as well decrease in the negative charge density on the oxygen atoms
      of the peptide bond carbonyl groups. Thus, EEF could control behavior and action
      of tripeptides, such as an increase in their catalytic activity. 

PMID- 25854877
TI  - PET imaging of insulin-like growth factor type 1 receptor expression with a 64Cu
      labeled Affibody molecule.
AB  - The insulin-like growth factor 1 receptor (IGF-1R) serves as an attractive target
      for cancer molecular imaging and therapy. Previous single photon emission
      computerized tomography (SPECT) studies showed that the IGF-1R-targeting Affibody
      molecules (99m)Tc-ZIGF1R:4551-GGGC, [(99m)Tc(CO)3](+)-(HE)3-ZIGF1R:4551 and
      (111)In-DOTA-ZIGF1R:4551 can discriminate between high and low IGF-1R-expression
      tumors and have the potential for patient selection for IGF-1R-targeted therapy.
      Compared with SPECT, positron emission tomography (PET) may improve imaging of
      IGF-1R-expression, because of its high sensitivity, high spatial resolution,
      strong quantification ability. The aim of the present study was to develop the
      (64)Cu-labeled NOTA-conjugated Affibody molecule ZIGF-1R:4:40 as a PET probe for
      imaging of IGF-1R-positive tumor. An Affibody analogue (Ac-Cys-ZIGF-1R:4:40)
      binding to IGF-1R was site-specifically conjugated with NOTA and labeled with
      (64)Cu. Binding affinity and specificity of (64)Cu-NOTA-ZIGF-1R:4:40 to IGF-1R
      were evaluated using human glioblastoma U87MG cells. Small-animal PET,
      biodistribution, and metabolic stability studies were conducted on mice bearing
      U87MG xenografts after the injection of (64)Cu-NOTA-ZIGF-1R:4:40 with or without
      co-injection of unlabeled Affibody proteins. The radiosynthesis of (64)Cu-NOTA
      ZIGF-1R:4:40 was completed successfully within 60 min with a decay-corrected
      yield of 75 %. (64)Cu-NOTA-ZIGF-1R:4:40 bound to IGF-1R with low nanomolar
      affinity (K D = 28.55 +/- 3.95 nM) in U87MG cells. (64)Cu-NOTA-ZIGF-1R:4:40 also
      displayed excellent in vitro and in vivo stability. In vivo biodistribution and
      PET studies demonstrated targeting of U87MG gliomas xenografts was IGF-1R
      specific. The tumor uptake was 5.08 +/- 1.07 %ID/g, and the tumor to muscle ratio
      was 11.89 +/- 2.16 at 24 h after injection. Small animal PET imaging studies
      revealed that (64)Cu-NOTA-ZIGF-1R:4:40 could clearly identify U87MG tumors with
      good contrast at 1-24 h after injection. This study demonstrates that (64)Cu-NOTA
      ZIGF-1R:4:40 is a promising PET probe for imaging IGF-1R positive tumor. 

PMID- 25854878
TI  - Featured Article: microRNA-125a in pulmonary hypertension: Regulator of a
      proliferative phenotype of endothelial cells.
AB  - Vascular remodeling due to excessive proliferation of endothelial and smooth
      muscle cells is a hallmark feature of pulmonary hypertension. microRNAs (miRNAs)
      are a class of small, non-coding RNA fragments that have recently been associated
      with remodeling of pulmonary arteries, in particular by silencing the bone
      morphogenetic protein receptor type II (BMPR2). Here we identified a novel
      pathway involving the concerted action of miR-125a, BMPR2 and cyclin-dependent
      kinase inhibitors (CDKN) that controls a proliferative phenotype of endothelial
      cells. An in silico approach predicted miR-125a to target BMPR2. Functional
      inhibition of miR-125a resulted in increased proliferation of these cells, an
      effect that was found accompanied by upregulation of BMPR2 and reduced expression
      of the tumor suppressors CDKN1A (p21) and CDKN2A (p16). These data were confirmed
      in experimental pulmonary hypertension in vivo. Levels of miR-125a were elevated
      in lung tissue of hypoxic animals that develop pulmonary hypertension. In
      contrast, circulating levels of miR-125a were found to be lower in mice with
      pulmonary hypertension as compared to control mice. Similar findings were
      observed in a small cohort of patients with precapillary pulmonary hypertension.
      These translational data emphasize the pathogenetic role of miR-125a in pulmonary
      vascular remodeling. 

PMID- 25854880
TI  - Late breaking trials of 2014 in structural heart disease and peripheral arterial
      disease: Commentary covering ACC, EuroPCR, SCAI, TCT, VIVA, ESC, and AHA.
AB  - With the plethora of clinical trials, it is difficult for busy interventional
      cardiologists to stay up to date. Therefore, the SCAI Publications Committee
      concisely summarizes and provides editorial commentary on the most important
      structural heart and peripheral arterial disease trials from the large
      international meetings of 2014. The intent is to allow quick assimilation of
      trial results into interventional practice.

PMID- 25854881
TI  - Recommendations on reporting requirements for flavonoids in research.
AB  - Numerous observational and intervention-based human studies support the notion of
      a beneficial role for dietary flavonoids in human health. Despite these studies,
      it is not yet possible to make dietary recommendations with regard to the types
      and amounts of flavonoids to be consumed. The inherent diversity of flavonoid
      structure, chemistry, and natural distribution in foods lends itself to errors in
      reporting the types and/or amounts of flavonoids consumed, as well as incomplete
      recognition of requirements for intervention studies that aim to assess their
      benefits in a clinical setting. A need exists for guidelines that facilitate the
      design and reporting of flavonoid research. With a focus on clinical studies,
      this article 1) outlines limitations commonly encountered in the field of
      flavonoid research, including the inconsistent use of nomenclature, inappropriate
      analytic methods, inconsistent use of existing flavonoid databases, and the lack
      of full consideration in the design of test materials for intervention trials,
      and 2) provides guidance for future studies with a focus on clinical intervention
      trials. Adoption of this guidance will facilitate more accurate and interpretable
      research that will support the development of dietary recommendations regarding
      the intake of flavonoids. 

PMID- 25854883
TI  - New climate velocity algorithm is nearly equivalent to simple species
      distribution modeling methods.

PMID- 25854879
TI  - Targeting TNF-related apoptosis-inducing ligand (TRAIL) receptor by natural
      products as a potential therapeutic approach for cancer therapy.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been shown to
      selectively induce apoptotic cell death in various tumor cells by engaging its
      death-inducing receptors (TRAIL-R1 and TRAIL-R2). This property has led to the
      development of a number of TRAIL-receptor agonists such as the soluble
      recombinant TRAIL and agonistic antibodies, which have shown promising anticancer
      activity in preclinical studies. However, besides activating caspase-dependent
      apoptosis in several cancer cells, TRAIL may also activate nonapoptotic signal
      transduction pathways such as nuclear factor-kappa B, mitogen-activated protein
      kinases, AKT, and signal transducers and activators of transcription 3, which may
      contribute to TRAIL resistance that is being now frequently encountered in
      various cancers. TRAIL resistance can be overcome by the application of efficient
      TRAIL-sensitizing pharmacological agents. Natural compounds have shown a great
      potential in sensitizing cells to TRAIL treatment through suppression of distinct
      survival pathways. In this review, we have summarized both apoptotic and
      nonapoptotic pathways activated by TRAIL, as well as recent advances in
      developing TRAIL-receptor agonists for cancer therapy. We also briefly discuss
      combination therapies that have shown great potential in overcoming TRAIL
      resistance in various tumors.

PMID- 25854882
TI  - Changes in intake of protein foods, carbohydrate amount and quality, and long
      term weight change: results from 3 prospective cohorts.
AB  - BACKGROUND: Dietary guidelines recommend interchanging protein foods (e.g.,
      chicken for red meat), but they may be exchanged for carbohydrate-rich foods
      varying in quality [glycemic load (GL)]. Whether such exchanges occur and how
      they influence long-term weight gain are not established. OBJECTIVE: Our
      objective was to determine how changes in intake of protein foods, GL, and their
      interrelationship influence long-term weight gain. DESIGN: We investigated the
      association between 4-y changes in consumption of protein foods, GL, and their
      interaction with 4-y weight change over a 16- to 24-y follow-up, adjusted for
      other lifestyle changes (smoking, physical activity, television watching, sleep
      duration), body mass index, and all dietary factors simultaneously in 3
      prospective US cohorts (Nurses' Health Study, Nurses' Health Study II, and Health
      Professionals Follow-Up Study) comprising 120,784 men and women free of chronic
      disease or obesity at baseline. RESULTS: Protein foods were not interchanged with
      each other (intercorrelations typically <|0.05|) but with carbohydrate (negative
      correlation as low as -0.39). Protein foods had different relations with long
      term weight gain, with positive associations for meats, chicken with skin, and
      regular cheese (per increased serving/d, 0.13-1.17 kg; P = 0.02 to P < 0.001); no
      association for milk, legumes, peanuts, or eggs (P > 0.40 for each); and relative
      weight loss for yogurt, peanut butter, walnuts, other nuts, chicken without skin,
      low-fat cheese, and seafood (-0.14 to -0.71 kg; P = 0.01 to P < 0.001). Increases
      in GL were independently associated with a 0.42-kg greater weight gain per 50
      unit increase (P < 0.001). Significant interactions (P-interaction < 0.05)
      between changes in protein foods and GL were identified; for example, increased
      cheese intake was associated with weight gain when GL increased, with weight
      stability when GL did not change, and with weight loss when exchanged for GL
      (i.e., decrease in GL). CONCLUSION: Protein foods were commonly interchanged with
      carbohydrate, and changes in protein foods and GL interacted to influence long
      term weight gain.

PMID- 25854884
TI  - The bright incubate at night: sexual dichromatism and adaptive incubation
      division in an open-nesting shorebird.
AB  - Ornamentation of parents poses a high risk for offspring because it reduces
      cryptic nest defence. Over a century ago, Wallace proposed that sexual
      dichromatism enhances crypsis of open-nesting females although subsequent studies
      found that dichromatism per se is not necessarily adaptive. We tested whether
      reduced female ornamentation in a sexually dichromatic species reduces the risk
      of clutch depredation and leads to adaptive parental roles in the red-capped
      plover Charadrius ruficapillus, a species with biparental incubation. Males had
      significantly brighter and redder head coloration than females. During daytime,
      when visually foraging predators are active, colour-matched model males incurred
      a higher risk of clutch depredation than females, whereas at night there was no
      difference in depredation risk between sexes. In turn, red-capped plovers
      maintained a strongly diurnal/nocturnal division of parental care during
      incubation, with males attending the nest largely at night when visual predators
      were inactive and females incubating during the day. We found support for
      Wallace's conclusion that reduced female ornamentation provides a selective
      advantage when reproductive success is threatened by visually foraging predators.
      We conclude that predators may alter their prey's parental care patterns and
      therefore may affect parental cooperation during care.

PMID- 25854885
TI  - Tight coupling of primary production and marine mammal reproduction in the
      Southern Ocean.
AB  - Polynyas are areas of open water surrounded by sea ice and are important sources
      of primary production in high-latitude marine ecosystems. The magnitude of annual
      primary production in polynyas is controlled by the amount of exposure to solar
      radiation and sensitivity to changes in sea-ice extent. The degree of coupling
      between primary production and production by upper trophic-level consumers in
      these environments is not well understood, which prevents reliable predictions
      about population trajectories for species at higher trophic levels under
      potential future climate scenarios. In this study, we find a strong, positive
      relationship between annual primary production in an Antarctic polynya and pup
      production by ice-dependent Weddell seals. The timing of the relationship
      suggests reproductive effort increases to take advantage of high primary
      production occurring in the months after the birth pulse. Though the proximate
      causal mechanism is unknown, our results indicate tight coupling between
      organisms at disparate trophic levels on a short timescale, deepen our
      understanding of marine ecosystem processes, and raise interesting questions
      about why such coupling exists and what implications it has for understanding
      high-latitude ecosystems. 

PMID- 25854887
TI  - The interface between genetics and psychology: lessons from developmental
      dyslexia.
AB  - Developmental dyslexia runs in families, and twin studies have confirmed that
      there is a substantial genetic contribution to poor reading. The way in which
      discoveries in molecular genetics are reported can be misleading, encouraging us
      to think that there are specific genes that might be used to screen for disorder.
      However, dyslexia is not a classic Mendelian disorder that is caused by a
      mutation in a single gene. Rather, like many other common disorders, it appears
      to involve combined effects of many genes and environmental factors, each of
      which has a small influence, possibly supplemented by rare variants that have
      larger effects but apply to only a minority of cases. Furthermore, to see clearer
      relationships between genotype and phenotype, we may need to move beyond the
      clinical category of dyslexia to look at underlying cognitive deficits that may
      be implicated in other neurodevelopmental disorders. 

PMID- 25854886
TI  - Hybridization and pre-zygotic reproductive barriers in Plasmodium.
AB  - Sexual reproduction is an obligate step in the life cycle of many parasites,
      including the causative agents of malaria (Plasmodium). Mixed-species infections
      are common in nature and consequently, interactions between heterospecific
      gametes occur. Given the importance of managing gene flow across parasite
      populations, remarkably little is understood about how reproductive isolation
      between species is maintained. We use the rodent malaria parasites P. berghei and
      P. yoelii to investigate the ecology of mixed-species mating groups, identify
      proteins involved in pre-zygotic barriers, and examine their evolution.
      Specifically, we show that (i) hybridization occurs, but at low frequency; (ii)
      hybridization reaches high levels when female gametes lack the surface proteins
      P230 or P48/45, demonstrating that these proteins are key for pre-zygotic
      reproductive isolation; (iii) asymmetric reproductive interference occurs, where
      the fertility of P. berghei gametes is reduced in the presence of P. yoelii and
      (iv) as expected for gamete recognition proteins, strong positive selection acts
      on a region of P230 and P47 (P48/45 paralogue). P230 and P48/45 are leading
      candidates for interventions to block malaria transmission. Our results suggest
      that depending on the viability of hybrids, applying such interventions to
      populations where mixed-species infections occur could either facilitate or
      hinder malaria control. 

PMID- 25854888
TI  - Increasing frequency of low summer precipitation synchronizes dynamics and
      compromises metapopulation stability in the Glanville fritillary butterfly.
AB  - Climate change is known to shift species' geographical ranges, phenologies and
      abundances, but less is known about other population dynamic consequences. Here,
      we analyse spatio-temporal dynamics of the Glanville fritillary butterfly
      (Melitaea cinxia) in a network of 4000 dry meadows during 21 years. The results
      demonstrate two strong, related patterns: the amplitude of year-to-year
      fluctuations in the size of the metapopulation as a whole has increased, though
      there is no long-term trend in average abundance; and there is a highly
      significant increase in the level of spatial synchrony in population dynamics.
      The increased synchrony cannot be explained by increasing within-year spatial
      correlation in precipitation, the key environmental driver of population change,
      or in per capita growth rate. On the other hand, the frequency of drought during
      a critical life-history stage (early larval instars) has increased over the
      years, which is sufficient to explain the increasing amplitude and the expanding
      spatial synchrony in metapopulation dynamics. Increased spatial synchrony has the
      general effect of reducing long-term metapopulation viability even if there is no
      change in average metapopulation size. This study demonstrates how temporal
      changes in weather conditions can lead to striking changes in spatio-temporal
      population dynamics. 

PMID- 25854889
TI  - Predator mimicry, not conspicuousness, explains the efficacy of butterfly
      eyespots.
AB  - Large conspicuous eyespots on butterfly wings have been shown to deter predators.
      This has been traditionally explained by mimicry of vertebrate eyes, but recently
      the classic eye-mimicry hypothesis has been challenged. It is proposed that the
      conspicuousness of the eyespot, not mimicry, is what causes aversion due to
      sensory biases, neophobia or sensory overloads. We conducted an experiment to
      directly test whether the eye-mimicry or the conspicuousness hypothesis better
      explain eyespot efficacy. We used great tits (Parus major) as model predator, and
      tested their reaction towards animated images on a computer display. Birds were
      tested against images of butterflies without eyespots, with natural-looking
      eyespots, and manipulated spots with the same contrast but reduced resemblance to
      an eye, as well as images of predators (owls) with and without eyes. We found
      that mimetic eyespots were as effective as true eyes of owls and more efficient
      in eliciting an aversive response than modified, less mimetic but equally
      contrasting eyespots. We conclude that the eye-mimicry hypothesis explains our
      results better than the conspicuousness hypothesis and is thus likely to be an
      important mechanism behind the evolution of butterfly eyespots.

PMID- 25854890
TI  - Does natural selection favour taller stature among the tallest people on earth?
AB  - The Dutch are the tallest people on earth. Over the last 200 years, they have
      grown 20 cm in height: a rapid rate of increase that points to environmental
      causes. This secular trend in height is echoed across all Western populations,
      but came to an end, or at least levelled off, much earlier than in The
      Netherlands. One possibility, then, is that natural selection acted congruently
      with these environmentally induced changes to further promote tall stature among
      the people of the lowlands. Using data from the LifeLines study, which follows a
      large sample of the population of the north of The Netherlands (n = 94 516), we
      examined how height was related to measures of reproductive success (as a proxy
      for fitness). Across three decades (1935-1967), height was consistently related
      to reproductive output (number of children born and number of surviving
      children), favouring taller men and average height women. This was despite a
      later age at first birth for taller individuals. Furthermore, even in this low
      mortality population, taller women experienced higher child survival, which
      contributed positively to their increased reproductive success. Thus, natural
      selection in addition to good environmental conditions may help explain why the
      Dutch are so tall. 

PMID- 25854891
TI  - GnRH agonist during luteal phase in women undergoing assisted reproductive
      techniques: systematic review and meta-analysis of randomized controlled trials.
AB  - OBJECTIVE: To identify, evaluate and summarize the available evidence regarding
      the effectiveness and safety of administering a gonadotropin releasing hormone
      (GnRH) agonist during the luteal phase in women undergoing assisted reproductive
      techniques. METHODS: In this systematic review and meta-analysis, we searched for
      randomized controlled trials (RCTs) comparing the addition of a GnRH agonist
      during the luteal phase, compared with standard luteal-phase support. We searched
      seven electronic databases and hand-searched the reference lists of included
      studies and related reviews. Our primary outcome was live birth or ongoing
      pregnancy per randomized woman. Our secondary outcomes were clinical pregnancy
      per randomized woman, miscarriage per clinical pregnancy, adverse perinatal
      outcome and congenital malformations. RESULTS: The evidence from eight studies
      examining 2776 women showed a relative risk (RR) for live birth or ongoing
      pregnancy of 1.26 (95% CI, 1.04-1.53; I(2) = 58%). Sensitivity analysis when
      excluding the studies that did not report live birth and those at high risk of
      bias resulted in one study examining 181 women with an RR of 1.07 (95% CI, 0.73
      1.58). Subgroup analysis separating the studies by single/multiple doses of GnRH
      agonists or by ovarian stimulation with GnRH agonist/antagonist was unable to
      explain the observed heterogeneity. The quality of the evidence was deemed to be
      very low: it was downgraded because of the limitation of the included studies,
      imprecision, inconsistency across the studies' results, and suspicion of
      publication bias. None of the included studies reported adverse perinatal
      outcomes or congenital malformations. CONCLUSIONS: There is evidence that adding
      GnRH agonist during the luteal phase improves the likelihood of ongoing
      pregnancy. However, this evidence is of very low quality and there is no evidence
      for adverse perinatal outcome and congenital malformations. We therefore believe
      that including this intervention in clinical practice would be premature.

PMID- 25854892
TI  - Automated data evaluation and modelling of simultaneous (19) F-(1) H medium
      resolution NMR spectra for online reaction monitoring.
AB  - Medium-resolution nuclear magnetic resonance spectroscopy (MR-NMR) currently
      develops to an important analytical tool for both quality control and process
      monitoring. In contrast to high-resolution online NMR (HR-NMR), MR-NMR can be
      operated under rough environmental conditions. A continuous re-circulating stream
      of reaction mixture from the reaction vessel to the NMR spectrometer enables a
      non-invasive, volume integrating online analysis of reactants and products. Here,
      we investigate the esterification of 2,2,2-trifluoroethanol with acetic acid to
      2,2,2-trifluoroethyl acetate both by (1) H HR-NMR (500 MHz) and (1) H and (19) F
      MR-NMR (43 MHz) as a model system. The parallel online measurement is realised by
      splitting the flow, which allows the adjustment of quantitative and independent
      flow rates, both in the HR-NMR probe as well as in the MR-NMR probe, in addition
      to a fast bypass line back to the reactor. One of the fundamental acceptance
      criteria for online MR-MNR spectroscopy is a robust data treatment and evaluation
      strategy with the potential for automation. The MR-NMR spectra are treated by an
      automated baseline and phase correction using the minimum entropy method. The
      evaluation strategies comprise (i) direct integration, (ii) automated line
      fitting, (iii) indirect hard modelling (IHM) and (iv) partial least squares
      regression (PLS-R). To assess the potential of these evaluation strategies for MR
      NMR, prediction results are compared with the line fitting data derived from the
      quantitative HR-NMR spectroscopy. Although, superior results are obtained from
      both IHM and PLS-R for (1) H MR-NMR, especially the latter demands for elaborate
      data pretreatment, whereas IHM models needed no previous alignment. Copyright (c)
      2015 John Wiley & Sons, Ltd. 

PMID- 25854893
TI  - Minimal change multiple system atrophy: an aggressive variant?
AB  - BACKGROUND: Glial cytoplasmic inclusions containing alpha-synuclein are the
      pathological hallmark of multiple system atrophy (MSA). Minimal change (MC-MSA)
      is an unusual MSA subtype with neuronal loss largely restricted to the substantia
      nigra and locus coeruleus. METHODS: Immunohistochemistry on selected brain
      regions and semiquantitative assessment were performed on six MC-MSA and eight
      MSA control cases. RESULTS: More neuronal cytoplasmic inclusions were seen in the
      caudate and substantia nigra in MC-MSA than in MSA controls (P = 0.002), without
      any statistical difference in glial cytoplasmic inclusion load in any region.
      Severe glial cytoplasmic inclusion load was found in the ventrolateral medulla (P
      = 1.0) and nucleus raphe obscurus (P = 0.4) in both groups. When compared with
      MSA controls, the three MC-MSA cases who had died of sudden unexpected death had
      an earlier age of onset (mean: 38 vs. 57.6 y, P = 0.02), a numerically shorter
      disease duration (mean: 5.3 vs. 8 y, P = 0.2) and a more rapid clinical
      progression with most of the clinical milestones reached within 3 y of
      presentation, suggesting an aggressive variant of MSA. Another three MC-MSA
      cases, who had died of unrelated concurrent diseases, had an age of onset (mean:
      57.7 y) and temporal course similar to controls, had less severe neuronal loss
      and gliosis in the medial and dorsolateral substantia nigra subregions (P < 0.05)
      than in MSA controls, and could be considered as a unique group with interrupted
      pathological progression. Significant respiratory dysfunction and early
      orthostatic hypotension were observed in all MC-MSA cases. CONCLUSIONS: Our
      findings could suggest that alpha-synuclein-associated oligodendroglial pathology
      may lead to neuronal dysfunction sufficient to cause clinical symptoms before
      overt neuronal loss in MSA. (c) 2015 International Parkinson and Movement
      Disorder Society.

PMID- 25854894
TI  - Assessing microbial competition in a hydrogen-based membrane biofilm reactor
      (MBfR) using multidimensional modeling.
AB  - The membrane biofilm reactor (MBfR) is a novel technology that safely delivers
      hydrogen to the base of a denitrifying biofilm via gas-supplying membranes. While
      hydrogen is an effective electron donor for denitrifying bacteria (DNB), it also
      supports sulfate-reducing bacteria (SRB) and methanogens (MET), which consume
      hydrogen and create undesirable by-products. SRB and MET are only competitive for
      hydrogen when local nitrate concentrations are low, therefore SRB and MET
      primarily grow near the base of the biofilm. In an MBfR, hydrogen concentrations
      are greatest at the base of the biofilm, making SRB and MET more likely to
      proliferate in an MBfR system than a conventional biofilm reactor. Modeling
      results showed that because of this, control of the hydrogen concentration via
      the intramembrane pressure was a key tool for limiting SRB and MET development.
      Another means is biofilm management, which supported both sloughing and erosive
      detachment. For the conditions simulated, maintaining thinner biofilms promoted
      higher denitrification fluxes and limited the presence of SRB and MET. The 2-d
      modeling showed that periodic biofilm sloughing helped control slow-growing SRB
      and MET. Moreover, the rough (non-flat) membrane assembly in the 2-d model
      provided a special niche for SRB and MET that was not represented in the 1-d
      model. This study compared 1-d and 2-d biofilm model applicability for simulating
      competition in counter-diffusional biofilms. Although more computationally
      expensive, the 2-d model captured important mechanisms unseen in the 1-d model.

PMID- 25854895
TI  - Imaging the C black formation by acetylene pyrolysis with molecular reactive
      force field simulations.
AB  - C black is a class of substantial materials with a long history of applications.
      However, apart from some descriptions of primary reactions, subsequent processes
      leading up to the final formation mechanism remain unclear. This mechanism is
      also crucial for understanding the formation of other carbonaceous materials. In
      this work, we visualize C black formation by acetylene pyrolysis using molecular
      dynamics simulations with a molecular reactive force field named ReaxFF. We find
      that the formation undergoes four stages: (1) chain elongation by H abstraction
      and polymerization of small C species, (2) chain branching, (3) cyclization and
      ring densification, and (4) condensed ring folding. The simulated C black
      particle possesses a structure of folded graphite layers, which is in good
      accordance with experimental observations. Cyclization and condensation are
      derived from fusion between neighboring chains, significantly varying from common
      experimental observations at relatively low temperatures that abide by the
      mechanism of H abstraction and C2H2 addition. Moreover, polyyne and polyene are
      usually found during acetylene pyrolysis, suggesting that the pyrolysis of
      acetylene and other hydrocarbons may be a feasible method of obtaining carbyne, a
      novel carbonaceous material with a high value. 

PMID- 25854896
TI  - Tricuspid Regurgitation and Mortality Risk Across Left Ventricular Systolic
      Function in Acute Heart Failure.
AB  - BACKGROUND: Tricuspid regurgitation (TR) is a common echocardiographic finding
      that has been related to adverse outcome under various clinical scenarios.
      Nevertheless, evidence supporting its prognostic value in heart failure (HF) is
      scarce, and, in most cases, contradictory. We evaluated the association of TR
      grade with 1-year all-cause mortality in acute HF (AHF). METHODS AND RESULTS: We
      included 1,842 consecutive patients admitted for AHF. Mean age was 72.8+/-11.3
      years, 51% were female and 45.5% had LVEF <50%. The severity of TR was graded in
      non-TR, mild (1), moderate (2), moderate-severe (3) and severe (4). At 1-year
      follow-up, 370 patients (20.1%) had died. In patients with LVEF >=50%, a
      significant and positive association between TR severity and mortality was noted.
      Indeed, the HR for mortality for TR 3 and 4 vs. no TR/TR 1 were as follows:
      hazard ratios (HR), 1.68; 95% confidence intervals (95% CI): 1.08-2.60, P=0.02;
      and HR, 2.87; 95% CI: 1.61-5.09, P<0.001, respectively. In contrast, no
      association between TR grade and mortality (P=0.650) was observed in patients
      with LVEF <50% (P-value for interaction=0.033). CONCLUSIONS: A differential
      prognostic effect of TR severity on 1-year mortality was observed for LVEF HF
      status. The association was significant only in patients with LVEF >=50%, with
      increasing mortality risk as TR became more severe.

PMID- 25854897
TI  - Investigating the quality of care in cardiovascular medicine.

PMID- 25854898
TI  - Ecotoxicity of two organophosphate pesticides chlorpyrifos and dichlorvos on non
      targeting cyanobacteria Microcystis wesenbergii.
AB  - Organophosphate pesticides (OPs), as a replacement for the organochlorine
      pesticides, are generally considered non-toxic to plants and algae. Chlorpyrifos
      and dichlorvos are two OPs used for pest control all over the world. In this
      study, the dose-response of cyanobacteria Microcystis wesenbergii on OPs exposure
      and the stimulating effect of OPs with and without phosphorus source were
      investigated. The results showed that high concentrations of chlorpyrifos and
      dichlorvos caused significant decrease of chlorophyll a content. The median
      inhibitory concentrations (EC50) of chlorpyrifos and dichlorvos at 96 h were
      15.40 and 261.16 MUmol L(-1), respectively. Growth of M. wesenbergii under low
      concentration of OPs (ranged from 1/10,000 to 1/20 EC50), was increased by 35.85
      % (chlorpyrifos) and 41.83 % (dichlorvos) at 120 h, respectively.
      Correspondingly, the highest enhancement on the maximum quantum yield (F v/F m)
      was 4.20 % (24 h) and 9.70 % (48 h), respectively. Chlorophyll fluorescence
      kinetics, known as O-J-I-P transients, showed significant enhancements in the O
      J, J-I, and I-P transients under low concentrations of dichlorvos at 144 h, while
      enhancements of chlorophyll fluorescence kinetics induced by low concentrations
      of chlorpyrifos were only observed in the J-I transient at 144 h. Significant
      decreases of chlorophyll content, F v/F m and O-J-I-P transients with OPs as sole
      phosphorus source were found when they were compared with inorganic phosphate
      treatments. The results demonstrated an evidently hormetic dose-response of M.
      wesenbergii to both chlorpyrifos and dichlorvos, where high dose (far beyond
      environmental concentrations) exposure caused growth inhibition and low dose
      exposure induced enhancement on physiological processes. The stimulating effect
      of two OPs on growth of M. wesenbergii was negligible under phosphate limitation.

PMID- 25854899
TI  - Disclosing haemophilia at school: strategies employed by mothers of children with
      haemophilia in Japan.
AB  - INTRODUCTION: Most children with haemophilia in Japan study in mainstream
      schools. However, many mothers have difficulty deciding whether to inform
      teachers of their child's haemophilia because of the accompanying potential
      discrimination and prejudice, particularly after the press coverage on the HIV
      scandal in the 1980s. AIMS: We therefore aim to explore and describe disclosure
      strategies of mothers of children with haemophilia. METHODS: A qualitative study
      was conducted using the modified grounded theory approach to explore disclosure
      strategies of mothers of children with haemophilia. Semi-structured interviews
      were conducted with 19 selected mothers (12 children were HIV positive and 7 were
      HIV-negative). RESULTS: In the pre-HIV/AIDS crisis period, the kind of strategy
      employed - full disclosure, conditional full disclosure and partial disclosure -
      depended on the extent of mothers' fears about mainstream schools refusing
      admission because of their child's haemophilia. After the HIV/AIDS crisis in the
      1980s in Japan, the three categories of strategies employed by mothers of
      children with haemophilia were limited disclosure, non-disclosure and full
      disclosure. These depended on mothers' expectations of discrimination towards
      their child because of the social stigma around haemophilia and being HIV
      positive. CONCLUSION: For children with haemophilia to feel safe attending
      school, public schools must establish care management and anti-discrimination
      systems for children with chronic diseases, thus assuring parents of their
      children's welfare at school.

PMID- 25854901
TI  - The Robustness and Effectiveness of the Triage System at Times of Overcrowding
      and the Extra Costs due to Inappropriate Use of Emergency Departments.
AB  - BACKGROUND: Overcrowding is one of the most harmful problems for Emergency
      Department (ED) management and the correct estimation of time resource absorption
      by each type of patient plays a strategic role in dealing with overcrowding and
      correctly programming ED activity. OBJECTIVE: We aimed to investigate how
      overcrowding may affect urgent patients' waiting times (i.e., the robustness of
      the triage patient priority system) and to evaluate the extra costs due to
      inappropriate use of EDs. METHODS: Data referring to 54,254 patients who accessed
      the ED of a major Italian hospital in 2011 were analyzed to study patient flows
      and overcrowding. To define an average per-patient cost, according to the
      severity of his or her health condition, the 2010 profit and loss account of the
      aforementioned hospital was studied and the time devoted by physicians to each
      type of patient was estimated by means of a self-reported survey. RESULTS:
      Empirical findings confirm a positive correlation between overcrowding and the
      time a patient has to wait before receiving treatment. This effect is relevant
      only for non-urgent patients who are responsible for the overcrowding itself.
      However, urgent patients' waiting times do not increase in the presence of
      overcrowding, confirming that the triage priority system is robust against the
      overcrowding situation. The analysis estimates, using 2010 data, that the actual
      per patient cost incurred by the hospital when treating white-coded patients is,
      on average, 36.54 euros; a green code costs 93.17, yellow 170.62, and red 227.62.
      It emerges that 4% of all the personnel costs are attributable to white color
      code assistance, 67% to green codes, 23% to yellow codes, and the remaining 6% to
      red codes. CONCLUSION: The implementation of effective policies intended to
      improve both efficiency and quality in providing emergency health services has to
      deal with the systemic problem of inappropriate use of EDs. Policy-makers should
      be aware of the fact that there is a considerable portion of ED demand for
      assistance that is inappropriate and that oversizing EDs with respect to the
      true, appropriate, urgent patients' demands, could bring about a further and
      undesirable rise in inappropriate assistance demands and, therefore, an increase
      in ED costs that are not consistent with their objectives.

PMID- 25854900
TI  - Effects of 5'-azacytidine and alendronate on a hepatocellular carcinoma cell
      line: a proteomics perspective.
AB  - Hepatocellular carcinoma (HCC) is the third leading cause of cancer related
      deaths around the world. Due to late diagnosis and development of drug resistance
      in patients suffering from HCC, development of more effective therapeutic
      strategies is inevitable. The aim of this study was to evaluate the combined
      apoptotic effect of 5'-Azacytidine (5'-AzaC) and alendronate (ALN) on Huh-7 HCC
      cell line and to explore differential expression at genomics and proteomics
      level. Incubation of HCC cell line with 5'-AzaC alone showed cell death in a time
      and dose dependent manner while in combination with ALN, increased cytotoxicity
      was observed. Up-regulation of CASP7(Caspase7) and LZTS1 (leucine zipper,
      putative tumor suppressor 1) and down-regulation of DNMT1(DNA (cytosine-5-)
      methyltransferase 1) was noted in treated cells. Proteomic studies on the treated
      cells revealed altered expression of different proteins including peroxiredoxin 2
      (Prx2), Annexin 5 (Anx5), Rho GTPase activating protein (RhoGAP), Nuclear factor
      kappa B (NF-kB), tumor necrosis factor alpha-induced protein (TNF),
      triosephosphate isomerase (TPI), Glutathione S transferase (GSTP1) and Heat shock
      protein60 (HSP60). Our study demonstrated the cytotoxic effect of 5'-AzaC and ALN
      drug combination on Huh-7 HCC cells suggesting such combinations may be explored
      as a possible therapeutic approach. Current study revealed that Huh-7 HCC cells
      are sensitive to 5'-AzaC and ALN drug combination and such combination approaches
      could lead to the development of new therapeutic strategies. Furthermore, we also
      report the expression of Anx5 exclusively in untreated cancerous cell line
      indicating the possibility of being used as a potential therapeutic target and
      biomarker.

PMID- 25854902
TI  - Blepharoptosis onset after topical prostaglandin therapy for glaucoma.

PMID- 25854903
TI  - Effects of dilatation types during percutaneous nephrolithotomy for less
      radiation exposure: a matched-pair pilot study.
AB  - AIM: To evaluate exposure to radiation during percutaneous nephrolithotomy (PCNL)
      by comparing balloon-type renal dilatation (BTRD) and amplatz-type renal
      dilatation (ATRD). MATERIALS AND METHODS: Retrospectively, 454 patients were
      documented and matched-pair analyses were performed. According to matched-paired
      criteria, in Group 1 (n = 78) BTRDs were used and in Group 2 (n = 78) ATRDs were
      used. Demographic, operative, and postoperative data including complications were
      recorded. Criteria for matched-pair analyses included age, gender, stone burden
      and localization, body mass index, presence of obstruction in intravenous
      urography, diabetes mellitus, previous extracorporeal shock wave lithotripsy
      and/or renal surgery even open and/or PCNL. RESULTS: The mean follow-up was 11.9
      +/- 1.1 months, and mean age was 44.8 +/- 13.7 years. Time to provide accessing
      into kidney, total time of exposure to X-ray, and time of exposure to X-ray until
      accessing into kidney were significantly lower in Group 1 than Group 2 (p <
      0.003, 0.006, and 0.039, respectively). CONCLUSIONS: BTRD may provide shorter
      exposure to radiation than ATRD for patients as well as operating room staff.
      Additionally, BTRD can provide rapid access into kidney than ATRD without
      significantly shorter operation time.

PMID- 25854905
TI  - The relationship between visfatin, liver inflammation, and acute phase reactants
      in chronic viral hepatitis B.
AB  - Chronic viral hepatitis B (CHB) is an important cause of morbidity and mortality.
      Adipokine stimulation might play an important role in the pathogenesis of chronic
      inflammation. The aim of this study was to evaluate serum visfatin concentrations
      and the relationship between visfatin, fibrosis, liver inflammation, and acute
      phase reactants in CHB patients.The sampling universe of the study consisted of
      41 CHB patients and 25 healthy controls. All patients had positive hepatitis B
      surface antigen (Hepatitis e antigen (HBeAg) positive n: 7, n: 34 HBeAg negative)
      for at least 6 months and detectable serum HBV DNA. Serum visfatin concentrations
      were significantly higher in the CHB patients [18.0 +/- 10.9 ng dL(-1)] than in
      the healthy controls [9.4 +/- 1.6 ng dL(-1)] [P < 0.001]. On the other hand,
      fibrinogen and haptoglobin concentrations were significantly lower in CHB
      patients. A strong negative correlation was observed between serum visfatin
      concentration, haptoglobin, and fibrinogen levels; however, there was no
      significant correlation between visfatin, glucose, alanine aminotransferase,
      aspartate aminotransferase, BMI, Knodell score, fibrosis score, hepatitis B virus
      DNA, sedimentation, and C-reactive protein. Visfatin concentrations were elevated
      and visfatin was negatively correlated with haptoglobin and fibrinogen levels in
      CHB patients. 

PMID- 25854906
TI  - Relationship between neck circumference and overactive bladder in women with
      metabolic syndrome: a preliminary study.
AB  - PURPOSE: To investigate relationship between overactive bladder (OAB) and
      metabolic syndrome (MtS) by using neck circumference (NC). METHODS: In
      retrospective view of prospective collected data, 204 women with or without OAB
      were enrolled into study, between August 2012 and December 2013. All patients
      were administered OAB validated questionnaires (OAB-V8) and whose score was > 8
      were accepted as OAB. Patients were divided into two groups and group 1 consisted
      of patients with OAB, group 2 consisted of patients without OAB. Demographic data
      with anthropometric measurements and blood analyses were recorded. Statistical
      analyses including receiver operating characteristic (ROC) curves were performed;
      statistically significant p was < 0.05. RESULTS: Mean age was 41.06 +/- 9.78
      years. There were 115 (56.4 %) patients in group 1, and 89 (43.6 %) patients in
      group 2. OAB-V8 scores were significant higher in group 1 than group 2 (p <
      0.001). Waist circumference (WC) and NC measurements were statistical significant
      longer in group 1 than group 2 (p < 0.001). In multivariate logistic regression
      analyses age, body mass index, MtS, WC, and NC were statistical significant
      associated with OAB. In ROC curves, area under the curve (AUC) was 0.72 cm2 for
      relationship between OAB and WC (p < 0.001), and AUC was 0.73 cm2 for
      relationship between OAB and NC (p = 0.004). Cut-off NC and WC values for OAB
      were determined as 35.25 cm and 98.5 cm, respectively. CONCLUSIONS: OAB with
      metabolic syndrome seems like more common in women than in those without. NC may
      be a novel indicator for OAB in selected female patients with MtS.

PMID- 25854904
TI  - Diagnostic and prognostic value of sCD14-ST--presepsin for patients admitted to
      hospital intensive care unit (ICU).
AB  - BACKGROUND: Sepsis is a serious problem in intensive care units all over the
      world. Biomarkers could be useful to identify patients at risk. We focused
      especially on the performance of presepsin (sCD14-ST), compared to C-reactive
      protein (CRP), procalcitonin (PCT) and CD64, to determine its diagnostic and
      prognostic indications. METHODS: The study was conducted on 47 hospitalized
      patients after procedures, who were divided into three groups; systemic
      inflammatory response (SIRS), sepsis and septic shock. Expression of CD64 on
      neutrophils presented as CD64 index, sCD14-ST, CRP and PCT were measured in whole
      blood or plasma samples. All patients had standard samples like urine,
      respiratory tract samples etc. taken for culturing. Blood cultures were drawn to
      confirm bloodstream infection. RESULTS: Forty (85 %) patients had SIRS with
      bacterial infection and seven (15 %) patients had SIRS with no infection. All
      infections were confirmed with blood cultures. Biomarkers were evaluated in all
      patients. In patients with confirmed infection the values were high. The patients
      with bacterial infection showed statistical significance with CD64 index (p =
      0.003), CRP (p = 0.049) and sCD14-ST (p = 0.026), but not with PCT (p = 1.000).
      The severity of diagnosed SIRS was significant only with PCT (p < 0.001).
      CONCLUSION: CD64 index, CRP and sCD14-ST served as good parameters to determine
      possible infection in patients that needed intensive care after major procedures.
      Values of PCT were the only ones to predict SIRS severity and could distinguish
      between sepsis and severe sepsis or septic shock.

PMID- 25854907
TI  - The accuracy of urinary ultrasound in the diagnosis of urinary stone disease in
      patients with acute flank pain: is it influenced by the time of ultrasound
      performance during the day or week?
AB  - BACKGROUND: The aim of this article is to investigate the possible impact of
      timing of ultrasound (US) during the day or week on its diagnostic accuracy.
      METHODS: We analyzed the records of 500 patients who underwent an initial urinary
      US, followed by a noncontrast computed tomography (NCCT) for the assessment of
      urinary stone disease. The sensitivity, specificity, negative and positive
      predictive values, negative and positive likelihood ratio, and overall diagnostic
      accuracy rates of US and were analyzed at different times of the day or week.
      RESULTS: The specificity and diagnostic accuracy of urinary US showed a decline
      toward the middle of the week followed by a steady rise by the end of the week,
      higher sensitivity for urinary US was noticed around mid-week. On the other hand,
      when urinary US results are subgrouped according to the time of the day they are
      performed, the specificity remained generally stable but the sensitivity and
      diagnostic accuracy showed lowest levels between 11:00 a.m. and 02:00 p.m. and
      between 04:00 p.m. and 05:00 p.m. Although some observational differences between
      sensitivity, specificity, and diagnostic accuracy of urinary US performed at
      different times of the day or week are seen, these differences were not
      statistically significant. CONCLUSIONS: Our study showed no significant influence
      of US timing on its diagnostic accuracy. A larger randomized prospective series
      is necessary to evaluate the impact of different factors on "precision" and
      "accuracy" in US reporting and, hence, the diagnostic accuracy of urinary US in
      identifying urinary stone disease.

PMID- 25854908
TI  - The efficiency of endoclips in maintaining the gastrointestinal bleeding-related
      Dieulafoy's lesion.
AB  - BACKGROUND: Dieulafoy's lesion (DL) is a relatively uncommon medical condition
      characterized by a large tortuous arteriole in the submucosa of any part of
      gastrointestinal (GI) tract wall that bleeds via erosion likely caused in the
      submucosal surface by protrusion of the pulsatile arteriole. Compared with other
      endoscopic hemostatic techniques, clipping alone for DL is limited. AIMS: The aim
      of the present case series study is to identify common clinical and endoscopic
      features, rates of occurrence, to review the outcome of endoscopic management of
      upper GI tract DL, and to illustrate the use and the efficiency of endoclips in
      maintaining the GI bleeding due to DL. PATIENTS AND METHODS: This case series was
      conducted at Department of Gastroenterology, Diskapi Yildirim Beyazit Educational
      and Research Hospital. The patients who were admitted to the emergency department
      of Diskapi Yildirim Beyazit Educational and Research Hospital underwent
      gastrointestinal system (GIS) endoscopy between 2008 and 2013 and were assessed
      retrospectively. Five cases of GI bleeding related to DL were given endoscopic
      treatment with hemoclip application. Clinical data, endoscopic findings, and the
      effects of the therapy were evaluated. RESULTS: The median number of endoscopic
      hemoclips application in first endoscopy was 4 (2-9). Rebleeding developed in all
      patients who had hemoclips applied. Re-endoscopy was performed in three of these
      patients, which controlled the bleeding. Two patients were transferred to
      surgery. CONCLUSIONS: Combination of endoscopic injection and mechanical
      therapies seems a suitable method for maintaining upper GIS bleeding due to DL.
      Also, further studies are needed to better define the best endoscopic approach
      for the treatment of DL.

PMID- 25854909
TI  - Is iron-deficiency anemia associated with migraine? Is there a role for anxiety
      and depression?
AB  - BACKGROUND: In this study, we determined the frequency of migraine headache in
      iron-deficiency anemia (IDA) patients and whether it was related to anxiety,
      depression, and somatization. METHODS: We included 127 consecutive IDA patients
      into the study. All patients were asked validated questions about headache and
      migraine face-to-face. They were administered validated questionnaires for
      anxiety-depression The Hospital Anxiety and Depression Scale and somatization.
      The quality of life (QoL) disturbance associated with headache was marked on a 0
      10 VAS. RESULTS: Of all IDA patients, 79.5 % defined headache at any time of
      their life. In addition, 36.2 % of all IDA patients defined the criteria for
      migraine. IDA patients with migraine were more frequently smokers and had
      significantly lower hemoglobin and mean corpuscular volume values (p values <
      0.05). The IDA group with migraine had significantly higher mean anxiety score (p
      = 0.046) and headache-related QoL disturbance score (p = 0.021) than the IDA
      group without migraine. Migraine patients with aura had lower hemoglobin values
      (p = 0.02), higher depression scores (p = 0.005), and higher migraine-related QoL
      disturbance scores than others. CONCLUSIONS: IDA patients have a high frequency
      of migraine headache. The presence of anxiety and depression have great influence
      on the presence of migraine in IDA patients.

PMID- 25854910
TI  - Serum antioxidant enzymes activities and oxidative stress levels in patients with
      acute ischemic stroke: influence on neurological status and outcome.
AB  - BACKGROUND: Oxidative stress is well believed to play a role in the pathogenesis
      of acute ischemic stroke. Reports on antioxidant enzyme activities in patients
      with stroke are conflicting. Therefore, the aim of this study was to investigate
      serum antioxidant enzyme activities and oxidative stress levels in patients with
      acute ischemic stroke within 1st, 5th, and 21st day after stroke onset and also
      the relationship between these results and the clinical status of patients.
      METHODS: The current study comprised 45 patients with acute ischemic stroke and
      30 healthy controls. Serum malondialdehyde (MDA) levels, superoxide dismutase
      (SOD), glutathione peroxidase (GSH-Px), and catalase activities were measured
      spectrophotometrically. RESULTS: Serum MDA levels were significantly higher in
      acute ischemic stroke patients within 24 h after stroke onset than controls (p <
      0.05), whereas serum catalase activity was significantly lower (p < 0.05). There
      were no significant differences in GSH-Px and SOD activities. Serum catalase and
      SOD activities were significantly lower in fifth day than those of controls
      (both, p < 0.05) but GSH-Px activity and MDA levels did not change (p > 0.05).
      Serum SOD activity was significantly lower in 21st day compared to SOD activity
      of controls (p < 0.05) but MDA levels, GSH-Px, and CAT activities did not change
      significantly. CONCLUSIONS: Our study demonstrated that acute ischemic stroke
      patients have increased oxidative stress and decreased antioxidant enzymes
      activities. These findings indicated that an imbalance of oxidant and antioxidant
      status might play a role in the pathogenesis of acute ischemic stroke.

PMID- 25854911
TI  - Usefulness of liver test and controlled attenuation parameter in detection of
      nonalcoholic fatty liver disease in patients with chronic renal failure and
      coronary heart disease.
AB  - BACKGROUND: In recent years, nonalcoholic fatty liver disease (NAFLD) was
      recognized as an important factor in chronic kidney disease (CKD) pathogenesis.
      The concentrations of serum aminotransferases in both chronic dialysis and
      chronic renal failure (CRF) patients most commonly fall within the lower end of
      the range of normal values. The aim of the present study was to investigate the
      usefulness of four liver tests and four biological scores in detection of NAFLD
      in comparison with transient elastography (TE) findings in different groups of
      patients. METHODS: The study was cross-sectional analysis collected data from a
      single tertiary care center. Of 202 patents there were 52 patients with CKD, 50
      patients with end-stage renal disease (ESRD) treated with haemodialysis (HD), 50
      renal transplant recipients (RTRs) and 50 patients with proven coronary heart
      disease (CHD). Fifty sex- and age-matched individuals without NAFLD and with
      normal liver and kidney function tests served as controls. With the help of TE
      (FibroScan(r), Echosense SA, Paris, France), liver stiffness was selected as the
      parameter to quantify liver fibrosis and Controlled Attenuation Parameter (CAP)
      was used to detect and quantify liver steatosis. RESULTS: According to the CAP
      findings 76.9 %CKD patients, 82 %HD patients, 74 %RTRs and 69.1 % CHD patients
      had CAP > 238 dB.m(-1) and thus by definition NAFLD. We have found that ALT, AST
      and GGT levels were positively correlated with CAP values while ALT and AST
      showed positive correlation with liver stiffness acquired with TE only in CHD
      patients. According to TE findings APRI (AUC 0.796) and FIB-4 (AUC 0.790) scores
      were correlated with the presence of fibrosis, while HIS score was correlated
      with the presence of steatosis (AUC 0.867) only in CHD patients. CONCLUSION:
      Liver tests and biological scores are not useful for NAFLD detection in CRF
      patients. TE with CAP provides the opportunity of noninvasive screening for NAFLD
      as well as liver fibrosis in patients with CRF.

PMID- 25854912
TI  - Loneliness and the social monitoring system: Emotion recognition and eye gaze in
      a real-life conversation.
AB  - Based on the belongingness regulation theory (Gardner et al., 2005, Pers. Soc.
      Psychol. Bull., 31, 1549), this study focuses on the relationship between
      loneliness and social monitoring. Specifically, we examined whether loneliness
      relates to performance on three emotion recognition tasks and whether lonely
      individuals show increased gazing towards their conversation partner's faces in a
      real-life conversation. Study 1 examined 170 college students (Mage = 19.26; SD =
      1.21) who completed an emotion recognition task with dynamic stimuli (morph task)
      and a micro(-emotion) expression recognition task. Study 2 examined 130 college
      students (Mage = 19.33; SD = 2.00) who completed the Reading the Mind in the Eyes
      Test and who had a conversation with an unfamiliar peer while their gaze
      direction was videotaped. In both studies, loneliness was measured using the UCLA
      Loneliness Scale version 3 (Russell, 1996, J. Pers. Assess., 66, 20). The results
      showed that loneliness was unrelated to emotion recognition on all emotion
      recognition tasks, but that it was related to increased gaze towards their
      conversation partner's faces. Implications for the belongingness regulation
      system of lonely individuals are discussed.

PMID- 25854913
TI  - Hepatic lipid droplet biology: Getting to the root of fatty liver.
AB  - Hepatic steatosis is defined by the accumulation of lipid droplets (LDs). Once
      thought to be only inert energy storage depots, LDs are increasingly recognized
      as organelles that have important functions in hepatocytes beyond lipid storage.
      The lipid and protein composition of LDs is highly dynamic and influences their
      intrinsic metabolism and signaling properties, which ultimately links them to the
      changes in hepatic function. This concise review highlights recent discoveries in
      LD biology and unique aspects of hepatic LDs and their role in liver disease.

PMID- 25854915
TI  - Reaction of low-molecular-mass organoselenium compounds (and their sulphur
      analogues) with inflammation-associated oxidants.
AB  - Selenium is an essential trace element in mammals, with the majority specifically
      encoded as seleno-L-cysteine into a range of selenoproteins. Many of these
      proteins play a key role in modulating oxidative stress, via either direct
      detoxification of biological oxidants, or repair of oxidised residues. Both
      selenium- and sulphur-containing residues react readily with the wide range of
      oxidants (including hydrogen peroxide, radicals, singlet oxygen and hypochlorous,
      hypobromous, hypothiocyanous and peroxynitrous acids) that are produced during
      inflammation and have been implicated in the development of a range of
      inflammatory diseases. Whilst selenium has similar properties to sulphur, it
      typically exhibits greater reactivity with most oxidants, and there are
      considerable differences in the subsequent reactivity and ease of repair of the
      oxidised species that are formed. This review discusses the chemistry of low
      molecular-mass organoselenium compounds (e.g. selenoethers, diselenides and
      selenols) with inflammatory oxidants, with a particular focus on the reaction
      kinetics and product studies, with the differences in reactivity between selenium
      and sulphur analogues described in the selected examples. These data provide
      insight into the therapeutic potential of low-molecular-mass selenium-containing
      compounds to modulate the activity of both radical and molecular oxidants and
      provide protection against inflammation-induced damage. Progress in their
      therapeutic development (including modulation of potential selenium toxicity by
      strategic design) is demonstrated by a brief summary of some recent studies where
      novel organoselenium compounds have been used as wound healing or radioprotection
      agents and in the prevention of cardiovascular disease. 

PMID- 25854914
TI  - Detailed assessment of microvasculature markers in non-small cell lung cancer
      reveals potentially clinically relevant characteristics.
AB  - Tumor angiogenesis is important for the progression of cancer and is orchestrated
      by various factors associated with tumor vessels, tumor cells, and stromal cells.
      Angiogenic signaling in non-small cell lung cancer (NSCLC) needs to be further
      clarified, especially regarding existing and upcoming therapeutic approaches.
      Expression of CD34, CD105, Mel-CAM, VE-cadherin, D2-40, VEGF, VEGFR1, and VEGFR2
      was assessed immunohistochemically on a cohort of 371 well documented, surgically
      resected NSCLC using a standardized tissue microarray platform. Extensive
      clinical data and a postoperative follow-up period of up to 18 years allowed us
      to assess clinicopathological correlations in detail. Microvasculature in NSCLC
      was significantly denser at the tumor periphery as compared to the tumor center.
      Squamous cell carcinomas (SCC) were associated with a notably lower microvessel
      density (MVD) than adenocarcinomas (ACA). CD105 was present at significantly
      higher levels on stromal cells of ACA as compared to SCC. Expression of VE
      cadherin by tumor cells (6% of cases, mainly ACA) as well as decreased MVD in the
      tumor centers was independently associated with poor prognosis in the entire
      cohort. Low MVD in SCC might be related to lower efficacy of and fatal bleeding
      during therapy with bevacizumab. In other NSCLC entities for which treatment with
      VEGF inhibitors is studied in clinical trials, the predictive value of MVD for
      therapy response merits to be prospectively examined. Our data suggest that
      patients with ACA may be candidates for therapies targeting CD105. VE-cadherin is
      another promising target for therapy, but its expression also provides
      independent prognostic information.

PMID- 25854916
TI  - Phenylephrine is a frequent cause of periorbital allergic contact dermatitis.

PMID- 25854917
TI  - Probing the effect of minor groove interactions on the catalytic efficiency of
      DNAzymes 8-17 and 10-23.
AB  - DNAzymes (Dz) 8-17 and 10-23 are two widely studied and well-characterized RNA
      cleaving DNA catalysts. In an effort to further improve the understanding of the
      fragile interactions and dynamics of the enzymatic mechanism, this study examines
      the catalytic efficiency of minimally modified DNAzymes. Five single mutants of
      Dz8-17 and Dz10-23 were prepared by replacing the adenine residues in the
      corresponding catalytic cores with 3-deazaadenine units. Kinetic assays were used
      to assess the effect on the catalytic activity and thereby identify the
      importance of hydrogen bonding that arises from the N3 atoms. The results suggest
      that modifications at A15 and A15.0 of Dz8-17 have a significant influence and
      show a reduction in catalytic activity. Modification at each location in Dz10-23
      results in a decrease of the observed rate constants, with A12 appearing to be
      the most affected with a reduction of ~80% of kobs and ~25% of the maximal
      cleavage rate compared to the wild-type DNAzyme. On the other hand, modification
      of A12 in Dz8-17 showed an ~130% increase in kobs, thus unraveling a new
      potential site for the introduction of chemical modifications. A pH-profile
      analysis showed that the chemical cleavage step is rate-determining, regardless
      of the presence and/or location of the mutation. These findings point towards the
      importance of the N3-nitrogens of certain adenine nucleotides located within the
      catalytic cores of the DNAzymes for efficient catalytic activity and further
      suggest that they might directly partake in maintaining the appropriate tertiary
      structure. Therefore, it appears that minor groove interactions constitute an
      important feature of DNAzymes as well as ribozymes. 

PMID- 25854918
TI  - Profound Changes in Sex Hormone Levels during Cross-Sex Hormone Therapy of
      Transsexuals do not Alter Serum Cholesterol Acceptor Capacity.
AB  - INTRODUCTION: Men and postmenopausal women exhibit a higher risk for
      atherosclerosis than premenopausal women. These differences were often attributed
      to sex steroids, but the role of estrogen and testosterone in atherosclerosis are
      more complex than anticipated. Cross-sex hormone therapy of transsexuals is an
      interesting model, which has been used to study hormonal effects on serum lipid
      profile, insulin resistance, and body composition. However, studies on macrophage
      cholesterol efflux, the first step in reverse cholesterol transport, are not
      available. AIM: The aim of this study was to evaluate the effect of cross-sex
      hormone therapy in transsexuals on the capacity of serum to accept cholesterol
      from macrophages. METHODS: Cholesterol acceptor capacity (CAC) of serum from
      transsexuals before and after at least 6 months of hormone treatment was measured
      using macrophage tissue culture models. MAIN OUTCOME MEASURES: CAC of serum using
      the human acute monocytic leukemia cell line (THP-1 cells). RESULTS:
      Unexpectedly, the CAC of serum from male to female (MtF) transsexuals was not
      increased, but decreased after hormone therapy. Serum from female to male (FtM)
      transsexuals showed no changes in CAC. CONCLUSIONS: Despite drastic changes in
      hormone status, no increase in CAC was detected in MtF patients, and no
      alteration in CAC was seen in FtM patients. These data further challenge the
      traditional view that estrogen and testosterone exert beneficial and detrimental
      effects, respectively, on lipoprotein metabolism and ultimately atherosclerosis.

PMID- 25854919
TI  - The broad-spectrum receptor tyrosine kinase inhibitor dovitinib suppresses growth
      of BRAF-mutant melanoma cells in combination with other signaling pathway
      inhibitors.
AB  - BRAF inhibitors have revolutionized treatment of mutant BRAF metastatic
      melanomas. However, resistance develops rapidly following BRAF inhibitor
      treatment. We have found that BRAF-mutant melanoma cell lines are more sensitive
      than wild-type BRAF cells to the small molecule tyrosine kinase inhibitor
      dovitinib. Sensitivity is associated with inhibition of a series of known
      dovitinib targets. Dovitinib in combination with several agents inhibits growth
      more effectively than either agent alone. These combinations inhibit BRAF-mutant
      melanoma and colorectal carcinoma cell lines, including cell lines with intrinsic
      or selected BRAF inhibitor resistance. Hence, combinations of dovitinib with
      second agents are potentially effective therapies for BRAF-mutant melanomas,
      regardless of their sensitivity to BRAF inhibitors. 

PMID- 25854920
TI  - Senescent cells communicate via intercellular protein transfer.
AB  - Mammalian cells mostly rely on extracellular molecules to transfer signals to
      other cells. However, in stress conditions, more robust mechanisms might be
      necessary to facilitate cell-cell communications. Cellular senescence, a stress
      response associated with permanent exit from the cell cycle and the development
      of an immunogenic phenotype, limits both tumorigenesis and tissue damage.
      Paradoxically, the long-term presence of senescent cells can promote tissue
      damage and aging within their microenvironment. Soluble factors secreted from
      senescent cells mediate some of these cell-nonautonomous effects. However, it is
      unknown whether senescent cells impact neighboring cells by other mechanisms.
      Here we show that senescent cells directly transfer proteins to neighboring cells
      and that this process facilitates immune surveillance of senescent cells by
      natural killer (NK) cells. We found that transfer of proteins to NK and T cells
      is increased in the murine preneoplastic pancreas, a site where senescent cells
      are present in vivo. Proteomic analysis and functional studies of the transferred
      proteins revealed that the transfer is strictly dependent on cell-cell contact
      and CDC42-regulated actin polymerization and is mediated at least partially by
      cytoplasmic bridges. These findings reveal a novel mode of intercellular
      communication by which senescent cells regulate their immune surveillance and
      might impact tumorigenesis and tissue aging. 

PMID- 25854921
TI  - Clinical Applications of Cine Balanced Steady-State Free Precession MRI for the
      Evaluation of the Subarachnoid Spaces.
AB  - The purpose of this article is to review the physiology of normal brain and
      spinal cord motion in the subarachnoid space, principles of cine balanced steady
      state free precession (bSSFP) magnetic resonance imaging (MRI), clinical
      applications, and the pitfalls encountered with this technique. The brain and
      spinal cord are dynamic structures that move with each heartbeat due to
      transmitted arterial pulse waves. Conventional MRI sequences do not allow
      anatomic evaluation of the pulsatile movement of the neural structures in the
      subarachnoid space due to limitations in temporal resolution. Cine bSSFP MRI uses
      cardiac gating to evaluate dynamically the brain and spinal cord with high
      contrast and temporal resolution.Cine bSSFP can be used in the evaluation of
      idiopathic syringomyelia to assess an underlying treatable cause, including
      arachnoid bands, which are usually not well visualized with conventional MR
      sequences due to motion artifact. This MRI technique is also useful in the
      evaluation of intraspinal and intracranial arachnoid cysts and the degree of mass
      effect on the cord. Other applications include preoperative and postoperative
      evaluation of Chiari I malformation and the evaluation of lateral ventricular
      asymmetry. The major limitation of cine bSSFP is the presence of banding
      artifacts, which can be reduced by shimming and modifying other scan parameters.

PMID- 25854922
TI  - Antibiotic-free selection in biotherapeutics: now and forever.
AB  - The continuously improving sophistication of molecular engineering techniques
      gives access to novel classes of bio-therapeutics and new challenges for their
      production in full respect of the strengthening regulations. Among these biologic
      agents are DNA based vaccines or gene therapy products and to a lesser extent
      genetically engineered live vaccines or delivery vehicles. The use of antibiotic
      based selection, frequently associated with genetic manipulation of microorganism
      is currently undergoing a profound metamorphosis with the implementation and
      diversification of alternative selection means. This short review will present
      examples of alternatives to antibiotic selection and their context of application
      to highlight their ineluctable invasion of the bio-therapeutic world. 

PMID- 25854923
TI  - A left anterior extrapleural approach to adjust right ventricle-pulmonary artery
      shunt flow using hemostatic clips after the Norwood operation.
AB  - Adjusting right ventricle-pulmonary artery shunt flow with placement of
      hemostatic clips in the Norwood operation is a useful technique for precise
      control of pulmonary blood flow in the acute postoperative period. This report
      describes our technique for optimizing right ventricle-pulmonary artery shunt
      flow with metal clips through a left anterior extrapleural approach, which can be
      performed safely and minimally invasively without sternal reopening. This
      procedure may decrease morbidity and contribute to long-term clinical improvement
      in patients undergoing the Norwood operation.

PMID- 25854925
TI  - Limited experience, high body mass index and previous urethral surgery are risk
      factors for failure in open urethroplasty due to penile strictures.
AB  - OBJECTIVE: The aim of this study was to evaluate outcomes and possible risk
      factors for failure of open urethroplasty due to penile urethral strictures.
      MATERIALS AND METHODS: A retrospective chart review was undertaken of 90 patients
      with penile stricture undergoing 109 open urethroplasties between 2000 and 2011.
      In 80 urethroplasties, a one-stage procedure was performed: 68 of these had a
      pediculated penile skin flap, nine had a free buccal mucosal graft and three had
      a free skin graft. A two-stage procedure using buccal mucosa was performed in 29
      urethroplasties. Failure was defined as when further urethral instrumentation was
      needed. RESULTS: The mean age in the one-stage and two-stage groups were 50 and
      54 years, respectively. The success rates in the corresponding groups were 65%
      and 72%, with follow-up times of 63 and 40 months, respectively. Multivariable
      analyses disclosed body mass index (BMI) and previous urethral surgery to be
      significant risk factors for failure in the one-stage group. Failure over time
      significantly decreased during the study period. CONCLUSIONS: Both one- and two
      stage penile urethroplasty demonstrated success rates in line with previous
      reports. Limited experience, high BMI and previous urethral surgery appear to be
      associated with less favourable outcome.

PMID- 25854924
TI  - Targeting EZH2 for cancer therapy: progress and perspective.
AB  - Enhancer of Zeste Homolog 2 (EZH2) is the core component of the polycomb
      repressive complex 2 (PRC2), possessing the enzymatic activity in generating
      di/tri-methylated lysine 27 in histone H3. EZH2 has important roles during early
      development, and its dysregulation is heavily linked to oncogenesis in various
      tissue types. Accumulating evidences suggest a remarkable therapeutic potential
      by targeting EZH2 in cancer cells. The first part reviews current strategies to
      target EZH2 in cancers, and evaluates the available compounds and agents used to
      disrupt EZH2 functions. Then we provide insight to the future direction of the
      research on targeting EZH2 in different cancer types. We comprehensively discuss
      the current understandings of the 1) structure and biological activity of EZH2,
      2) its role during the assembling of PRC2 and recruitment of other protein
      components, 3) the molecular events directing EZH2 to target genomic regions, and
      4) post-translational modification at EZH2 protein. The discussion provides the
      basis to inspire the development of novel strategies to abolish EZH2-related
      effects in cancer cells. 

PMID- 25854926
TI  - The Effect of Psychological Distress and Personality Traits on Cognitive
      Performances and the Risk of Dementia in Patients with Mild Cognitive Impairment.
AB  - BACKGROUND: The relation between psychological distress, personality traits, and
      cognitive decline in cognitively impaired patients remains unclear. OBJECTIVE: To
      investigate the effect of psychological distress and personality traits on
      cognitive functioning in subjects with mild cognitive impairment (MCI); and to
      investigate the predictive accuracy of these factors for the development of
      dementia. METHODS: MCI patients (n = 343, age: 60.9+/-9.9 years, 38% female, and
      MMSE score: 28.1+/-1.9) were included from the Maastricht memory clinic. All
      patients underwent a standardized neuropsychological assessment (including tests
      for measuring mental speed (Trail Making Test (TMT) part A and Stroop Color Word
      Test (SCWT) part I), executive functioning (TMT part B and SCWT part III), memory
      (15-Word Learning Tests), and verbal fluency (1-minute animals)), CT or MRI, and
      blood assessment. The Dutch Personality Questionnaire (DPQ) and the 90-items
      Symptom Check List (SCL-90) were used to measure personality traits and
      psychological distress. Conversion to dementia was assessed two, five, and ten
      years after baseline. The mean follow-up period was 6.7+/-3.4 years. RESULTS: The
      Psychoneuroticism score of the SCL-90 was associated with slower performances on
      SCWT part I and TMT part A. The subdomain Neuroticism of the DPQ was also
      associated with slower scores on the TMT part A. At follow-up, 85 (25.9%)
      subjects had developed dementia. The SCL-90 total score, and the subscales,
      Anxiety, Somatization, Insufficiency in thought and action, and Sleeping problems
      were associated with a decreased risk for developing (AD-type) dementia.
      CONCLUSION: Psychological distress negatively affected information processing
      speed, but was not associated with an increased risk of developing dementia in
      patients with MCI.

PMID- 25854927
TI  - Severity of White Matter Hyperintensities and Length of Hospital Stay in Patients
      with Cognitive Impairment: A CREDOS (Clinical Research Center for Dementia of
      South Korea) Study.
AB  - BACKGROUND & OBJECTIVE: White matter hyperintensities (WMHs) contribute to
      aggravation of dementia or geriatric syndrome, thereby resulting in functional
      impairment. However, evidence of direct association between WMHs and medical
      resource utilization indicated by length of hospital stay (LOS) is scarce in
      patients with cognitive impairment. This study aimed to examine the relationship
      between the severity of WMHs and LOS in patients with cognitive impairment.
      METHODS: 4,253 older adults with cognitive impairment were enrolled in this
      study. We defined LOS as the total sum of days from January 1, 2008 to December
      31, 2012. The severity of periventricular (PVWMHs), deep (DWMHs), and overall
      white matter hyperintensities (Overall WMHs) was evaluated by a visual rating
      scale. We conducted multinomial logistic regression to demonstrate the
      relationship between LOS and severity of PVWHMs, DWHMs, and Overall WMHs,
      respectively. RESULTS: The median LOS was 20 days. Severe PVWMHs had a higher
      likelihood of longer LOS (Q3: odd ratio/OR = 1.32, 95% confidence interval/CI =
      1.06-1.64; Q4: OR = 1.33, 95% CI = 1.07-1.65; Q5: OR = 1.55, 95% CI = 1.26-1.91).
      As for DWMHs, moderate DWMHs were related to longer LOS (Q4: OR = 1.33, 95% CI =
      1.03-1.71; Q5: OR = 1.63, 95% CI = 1.26-2.11). Finally, severity of overall WMHs
      was independently associated with LOS, which was similar to the results of DWMHs.
      CONCLUSION: These findings would advocate for prevention of WMHs to stave off
      excess medical resource utilization in patients with cognitive impairment.

PMID- 25854928
TI  - Primary Progressive Speech Abulia.
AB  - BACKGROUND AND OBJECTIVE: Primary progressive aphasia (PPA) is a
      neurodegenerative disorder characterized by progressive language impairment. The
      three variants of PPA include the nonfluent/agrammatic, semantic, and logopenic
      types. The goal of this report is to describe two patients with a loss of speech
      initiation that was associated with bilateral medial frontal atrophy. METHODS AND
      RESULTS: Two patients with progressive speech deficits were evaluated and their
      examinations revealed a paucity of spontaneous speech; however their naming,
      repetition, reading, and writing were all normal. The patients had no evidence of
      agrammatism or apraxia of speech but did have impaired speech fluency. In
      addition to impaired production of propositional spontaneous speech, these
      patients had impaired production of automatic speech (e.g., reciting the Lord's
      Prayer) and singing. Structural brain imaging revealed bilateral medial frontal
      atrophy in both patients. CONCLUSION: These patients' language deficits are
      consistent with a PPA, but they are in the pattern of a dynamic aphasia. Whereas
      the signs-symptoms of dynamic aphasia have been previously described, to our
      knowledge these are the first cases associated with predominantly bilateral
      medial frontal atrophy that impaired both propositional and automatic speech.
      Thus, this profile may represent a new variant of PPA.

PMID- 25854930
TI  - Divalent Copper as a Major Triggering Agent in Alzheimer's Disease.
AB  - Alzheimer's disease (AD) is at epidemic proportions in developed countries, with
      a steady increase in the early 1900 s, and then exploding over the last 50 years.
      This epidemiology points to something causative in the environment of developed
      countries. This paper will review the considerable evidence that that something
      could be inorganic copper ingestion. The epidemic parallels closely the spread of
      copper plumbing, with copper leached from the plumbing into drinking water being
      a main causal feature, aided by the increasingly common use of supplement pills
      containing copper. Inorganic copper is divalent copper, or copper-2, while we now
      know that organic copper, or copper in foods, is primarily monovalent copper, or
      copper-1. The intestinal transport system, Ctr1, absorbs copper-1 and the copper
      moves to the liver, where it is put into safe channels. Copper-2 is not absorbed
      by Ctr1, and some of it bypasses the liver and goes directly into the blood,
      where it appears to be exquisitely toxic to brain cognition. Thus, while
      aggregation of amyloid-beta has been postulated to be the cause of AD under
      current dogma, the great increase in prevalence over the last century appears to
      be due to ingestion of copper-2, which may be causing the aggregation, and/or
      increasing the oxidant toxicity of the aggregates. An alternative hypothesis
      proposes that oxidant stress is the primary injuring agent, and under this
      hypothesis, copper-2 accumulation in the brain may be a causal factor of the
      oxidant injury. Thus, irrespective of which hypothesis is correct, AD can be
      classified, at least in part, as a copper-2 toxicity disease. It is relatively
      easy to avoid copper-2 ingestion, as discussed in this review. If most people
      begin avoiding copper-2 ingestion, perhaps the epidemic of this serious disease
      can be aborted.

PMID- 25854931
TI  - Associations between Homocysteine, Folic Acid, Vitamin B12 and Alzheimer's
      Disease: Insights from Meta-Analyses.
AB  - The associations between homocysteine (Hcy), folic acid, and vitamin B12 and
      Alzheimer's disease (AD) have gained much interest, while remaining
      controversial. We aim to perform meta-analyses to evaluate comprehensively: i)
      Hcy, folic acid, and vitamin B12 levels in AD patients in comparison with
      controls; and ii) the association between Hcy, folic acid, and vitamin B12 levels
      and risk of AD. A literature search was performed using Medline and Scopus
      databases. A total of 68 studies were identified and included in the meta
      analyses. Stata 12.0 statistical software was used to perform the meta-analyses.
      First, AD patients may have higher level of Hcy, and lower levels of folate and
      vitamin B12 in plasma than controls. Further age-subgroup analysis showed no age
      effect for Hcy levels in plasma between AD patients and matched controls, while
      the differences in folate and vitamin B12 levels further enlarged with increased
      age. Second, data suggests that high Hcy and low folate levels may correlate with
      increased risk of AD occurrence. The comprehensive meta-analyses not only
      confirmed higher Hcy, lower folic acid, and vitamin B12 levels in AD patients
      than controls, but also implicated that high Hcy and low folic acid levels may be
      risk factors of AD. Further studies are encouraged to elucidate mechanisms
      linking these conditions.

PMID- 25854929
TI  - Neuropsychiatric Symptoms and Functional Connectivity in Mild Cognitive
      Impairment.
AB  - BACKGROUND: Neuropsychiatric symptoms (NPS), such as apathy and depression,
      commonly accompany cognitive and functional decline in early Alzheimer's disease
      (AD). Prior studies have shown associations between affective NPS and
      neurodegeneration of medial frontal and inferior temporal regions in mild
      cognitive impairment (MCI) and AD dementia. OBJECTIVE: To investigate the
      association between functional connectivity in four brain networks and NPS in
      elderly with MCI. METHODS: NPS were assessed using the Neuropsychiatric Inventory
      in 42 subjects with MCI. Resting-state functional connectivity in four networks
      (default mode network, fronto-parietal control network (FPCN), dorsal attention
      network, and ventral attention network) was assessed using seed-based magnetic
      resonance imaging. Factor analysis was used to identify two factors of NPS:
      Affective and Hyperactivity. Linear regression models were utilized with the
      neuropsychiatric factors as the dependent variable and the four networks as the
      predictors of interest. Covariates included age, gender, premorbid intelligence,
      processing speed, memory, head movement, and signal-to-noise ratio. These
      analyses were repeated with the individual items of the affective factor, using
      the same predictors. RESULTS: There was a significant association between greater
      Affective factor symptoms and reduced FPCN connectivity (p = 0.03). There was no
      association between the Hyperactivity factor and any of the networks. Secondary
      analyses revealed an association between greater apathy and reduced FPCN
      connectivity (p = 0.005), but none in other networks. CONCLUSIONS: Decreased
      connectivity in the FPCN may be associated with greater affective symptoms,
      particularly apathy, early in AD. These findings extend prior studies, using
      different functional imaging modalities in individuals with greater disease
      severity.

PMID- 25854932
TI  - The Effects of Bushen Capsule on Episodic Memory in Amnestic Mild Cognitive
      Impairment Patients: A Pilot Placebo Controlled fMRI Study.
AB  - BACKGROUND: Observing the effects of a drug on episodic memory and the underlying
      brain function has extreme significance in evaluating its therapeutic value in
      treating amnestic mild cognitive impairment (aMCI). OBJECTIVE: To observe the
      effects of Bushen capsule (BSC), a Chinese herbal medicine, on episodic memory in
      aMCI and further explore the underlying mechanism. METHODS: 44 aMCI patients from
      hospitals and local communities in Beijing were randomly divided into the BSC
      treatment group (22 patients orally treated with BSC) and the placebo group (22
      patients treated with placebo). The duration of intervention lasted for 3 months.
      Before and after the 3 months treatment, neuropsychological tests and fMRI
      examinations were carried out to assess cognitive ability and brain activation
      changes, respectively. RESULTS: Compared to the placebo group, the BSC group
      presented a significant increase in the AVLT(N5) (p = 0.003) and Stroop (C-B)
      time (p = 0.002). fMRI results showed a reduction of brain negative activation in
      the right middle temporal gyrus and a positive activation enhancement in the
      right putamen among the BSC group after treatment. Meanwhile, the variation in
      activation values in the right middle temporal gyrus was significantly correlated
      with the improvement in test values of AVLT(N5), and the variation in
      deactivation values in the right putamen was significantly correlated with the
      improvement in test values of Stroop (C-B) time. CONCLUSIONS: BSC can improve the
      behavioral performances of episodic memory in aMCI; this effect may be related to
      its modulation on the activations of the temporal lobe and the putamen under
      episodic memory encoding task.

PMID- 25854933
TI  - Antisense against Amyloid-beta Protein Precursor Reverses Memory Deficits and
      Alters Gene Expression in Neurotropic and Insulin-Signaling Pathways in SAMP8
      Mice.
AB  - The senescence-accelerated mouse (SAMP8) strain exhibits an age-related decrease
      in memory accompanied by an increase in hippocampal amyloid-beta protein
      precursor (AbetaPP) and amyloid-beta peptide (Abeta). We have shown that
      administration of an antisense oligonucleotide against the Abeta region of
      AbetaPP (AbetaPP antisense) reverses the memory deficits. The purpose of this
      study was to determine the effect of peripheral (IV) administration of AbetaPP
      antisense on hippocampal gene expression. The AbetaPP antisense reversed the
      memory deficits and altered expression of 944 hippocampal genes. Pathway analysis
      showed significant gene expression changes in nine pathways. These include the
      MAPK signaling pathway (p = 0.0078) and the phosphatidylinositol signaling
      pathway (p = 0.043), which we have previously shown to be altered in SAMP8 mice.
      The changes in these pathways contributed to significant changes in the
      neurotropin (p = 0.0083) and insulin signaling (p = 0.015) pathways, which are
      known to be important in learning and memory. Changes in these pathways were
      accompanied by phosphorylation changes in the downstream target proteins p70S6K,
      GSK3beta, ERK, and CREB. These changes in hippocampal gene expression and protein
      phosphorylation may suggest specific new targets for antisense therapy aimed at
      improving memory. 

PMID- 25854934
TI  - Lamotrigine Reduces beta-Site AbetaPP-Cleaving Enzyme 1 Protein Levels Through
      Induction of Autophagy.
AB  - Lamotrigine (LTG), a broad-spectrum anti-epileptic drug widely used in treatment
      for seizures, shows potential efficacy in Alzheimer's disease (AD) therapy.
      Chronic LTG treatment rescues the suppressed long-term potentiation, loss of
      spines and cognitive deficits in AbetaPP/PS1 mice, known to overexpress a
      chimeric mouse/human mutant amyloid-beta protein precursor (AbetaPP) and a mutant
      human presenilin 1 (PS1). These changes are accompanied by reduction of amyloid
      beta (Abeta) plaques density and of levels of beta-C-terminal fragment of AbetaPP
      (beta-CTF), a fragment of AbetaPP cleaved by beta-secretase. These results
      suggest LTG treatment reduces Abeta production, possibly through modulation of
      cleavage of AbetaPP by beta-secretase. However, the underlying mechanisms still
      remain unclear. In this study, decreased protein levels, but not mRNA levels of
      beta-site AbetaPP-cleaving enzyme 1 (BACE1), were observed in cultured HEK293
      cells and the brains of AbetaPP/PS1 transgenic mice upon LTG treatment. Moreover,
      LTG treatment suppressed mammalian target of rapamycin (mTOR) signaling, while
      enhancing activation of cAMP response element binding protein (CREB), two
      signaling pathways essential for autophagy induction. LTG treatment increased the
      numbers of LC3-GFP + puncta and LC3-II levels in HEK293 cells, indicating an
      induction of autophagy. The downregulation of BACE1 by LTG treatment was
      prevented by the autophagy inhibitor 3-Methyladenine. Therefore, this study shows
      that LTG treatment reduces the protein levels of BACE1 through activation of
      autophagy, possibly via inhibition of mTOR signaling and activation of CREB. 

PMID- 25854936
TI  - Outcomes in splenic marginal zone lymphoma: analysis of 107 patients treated in
      British Columbia.
AB  - Splenic marginal zone lymphoma (SMZL) accounts for less than 2% of all non
      Hodgkin lymphomas. We identified 107 cases diagnosed with SMZL between 1985 and
      2012 from the British Columbia Cancer Agency Centre for Lymphoid Cancer and
      Lymphoma Pathology Databases. Patient characteristics were: median age 67 years
      (range 30-88), male 40%, stage IV 98%, splenomegaly 93%, bone marrow involvement
      96%, peripheral blood involvement 87%. As initial treatment, 52 underwent
      splenectomy (10 with chemotherapy), 38 chemotherapy alone (21 chemoimmunotherapy
      containing rituximab, 1 rituximab alone), two antivirals for hepatitis C, and 15
      were only observed. The 10-year overall survival for first-line splenectomy
      versus chemotherapy was 61% and 42%, respectively [Hazard Ratio (HR) 0.48, 95%
      confidence interval (CI) 0.26-0.88, P = 0.017]. The 10-year failure-free survival
      (FFS) after first-line splenectomy vs chemotherapy was 39% and 14%, respectively
      (HR 0.48, 95% CI 0.28-0.80, P = 0.004). Among the 38 patients who received first
      line chemotherapy, FFS was similar between those receiving rituximab (n = 22) and
      those who did not (n = 16) (HR 0.64, 95% CI 0.31-1.34, P = 0.238). Fifteen
      patients transformed to aggressive lymphoma with median time to transformation of
      3.5 years (range 6 months to 12 years) and the 10-year transformation rate was
      18%. In conclusion, splenectomy remains a reasonable treatment for patients with
      SMZL.

PMID- 25854937
TI  - A statistical method for studying correlated rare events and their risk factors.
AB  - Longitudinal studies of rare events such as cervical high-grade lesions or
      colorectal polyps that can recur often involve correlated binary data. Risk
      factor for these events cannot be reliably examined using conventional
      statistical methods. For example, logistic regression models that incorporate
      generalized estimating equations often fail to converge or provide inaccurate
      results when analyzing data of this type. Although exact methods have been
      reported, they are complex and computationally difficult. The current paper
      proposes a mathematically straightforward and easy-to-use two-step approach
      involving (i) an additive model to measure associations between a rare or
      uncommon correlated binary event and potential risk factors and (ii) a
      permutation test to estimate the statistical significance of these associations.
      Simulation studies showed that the proposed method reliably tests and accurately
      estimates the associations of exposure with correlated binary rare events. This
      method was then applied to a longitudinal study of human leukocyte antigen (HLA)
      genotype and risk of cervical high grade squamous intraepithelial lesions (HSIL)
      among HIV-infected and HIV-uninfected women. Results showed statistically
      significant associations of two HLA alleles among HIV-negative but not HIV
      positive women, suggesting that immune status may modify the HLA and cervical
      HSIL association. Overall, the proposed method avoids model nonconvergence
      problems and provides a computationally simple, accurate, and powerful approach
      for the analysis of risk factor associations with rare/uncommon correlated binary
      events.

PMID- 25854935
TI  - Pathogenesis of neonatal necrotizing enterocolitis.
AB  - Although necrotizing enterocolitis (NEC) is the most lethal gastrointestinal
      disease in the neonatal population, its pathogenesis is poorly understood. Risk
      factors include prematurity, bacterial colonization, and formula feeding. This
      review examines how mucosal injury permits opportunistic pathogens to breach the
      gut barrier and incite an inflammatory response that leads to sustained
      overproduction of mediators such as nitric oxide and its potent adduct,
      peroxynitrite. These mediators not only exacerbate the initial mucosal injury,
      but they also suppress the intestinal repair mechanisms, which further
      compromises the gut barrier and culminates in bacterial translocation, sepsis,
      and full-blown NEC. 

PMID- 25854939
TI  - Sensitivity of nonlinear photoionization to resonance substructure in collective
      excitation.
AB  - Collective behaviour is a characteristic feature in many-body systems, important
      for developments in fields such as magnetism, superconductivity, photonics and
      electronics. Recently, there has been increasing interest in the optically
      nonlinear response of collective excitations. Here we demonstrate how the
      nonlinear interaction of a many-body system with intense XUV radiation can be
      used as an effective probe for characterizing otherwise unresolved features of
      its collective response. Resonant photoionization of atomic xenon was chosen as a
      case study. The excellent agreement between experiment and theory strongly
      supports the prediction that two distinct poles underlie the giant dipole
      resonance. Our results pave the way towards a deeper understanding of collective
      behaviour in atoms, molecules and solid-state systems using nonlinear
      spectroscopic techniques enabled by modern short-wavelength light sources. 

PMID- 25854938
TI  - Persistent activation of STAT3 by PIM2-driven positive feedback loop for
      epithelial-mesenchymal transition in breast cancer.
AB  - Metastasis of breast cancer is promoted by epithelial-mesenchymal transition
      (EMT). Emerging evidence suggests that STAT3 is a critical signaling node in EMT
      and is constitutively activated in many carcinomas, including breast cancer.
      However, its signaling mechanisms underlying persistent activation of STAT3
      associated with EMT remain obscure. Here, we report that PIM2 promotes activation
      of STAT3 through induction of cytokines. Activation of STAT3 caused an increase
      in PIM2 expression, implicating a positive feedback loop between PIM2 and STAT3.
      In agreement, targeting of either PIM2, STAT3 or PIM2-dependent cytokines
      suppressed EMT-associated migratory and invasive properties through inhibition of
      ZEB1. Taken together, our findings identify the signaling mechanisms underlying
      the persistent activation of STAT3 and the oncogenic role of PIM2 in EMT in
      breast cancer.

PMID- 25854940
TI  - [Current concepts in diagnostics and therapy of diabetes mellitus].
AB  - In Germany approximately 7.2% of the population currently suffer from diabetes
      mellitus. A further increase in the prevalence is expected in the coming years.
      Many therapy options, sometimes even without a risk of hypoglycemia, are now
      available. The foundations of a sufficient therapy of type 2 diabetes are,
      however, still lifestyle measures, such as weight reduction, optimized nutrition
      and increased physical activity. Optimization of cardiac and cerebrovascular risk
      factors is also an essential component of management of diabetes in order to
      reduce or even avoid secondary complications.

PMID- 25854941
TI  - Highlight: dynamics of thiol-based redox switches.

PMID- 25854942
TI  - [Hospice palliative care is a universal value and the essence of nursing].
AB  - This article uses four examples to illustrate the recent rise of hospice
      palliative care as a universal value. These examples include the story of Dame
      Cecily Saunders, the pioneer of the palliative care movement in the U.K.; the
      national healthcare plan currently promoted by United States' President Obama; a
      survey on the topic of quality of death in 40 countries conducted by the Lien
      Foundation (Singapore); and the story of the Hospice Movement in Taiwan. This
      article further describes how hospice palliative care has changed the healthcare
      culture and presents the World Health Organization's definition of palliative
      care and the implications of this definition. Additionally, this article
      identifies the common palliative-care mistakes that have been made by the general
      public and by healthcare workers. Healthcare professionals must acquire essential
      relevant knowledge and skills in order to ensure that hospice palliative care
      addresses the needs of terminally ill patients adequately. Finally, the author
      describes a novel approach to instilling proper palliative-care concepts and
      practices that is entitled Life, Peace, Care, and Honor (LPCH or the "3344"
      concept). 

PMID- 25854943
TI  - [Hospice palliative care policy in Taiwan: past developments and future
      perspectives].
AB  - The duty of medical personnel is to save lives, cure diseases, relieve suffering,
      and promote health. Medical personnel care for their patients from birth to
      death. At the end of terminal care, medical personnel should maintain a religious
      / holistic commitment to their patients to "remove their suffering and provide
      happiness" as much as possible. Mackay Hospital opened the first hospice in
      Taiwan in 1990. Financial coverage of hospice care by the National Health
      Insurance, the enactment of the Hospice Palliative Act, the attention of Hospital
      Accreditation to hospice care, and the establishment of the system of clinical
      chaplaincy have all contributed to the development of hospice palliative care in
      Taiwan. Application of the Taiwan Coma Scale has been shown to decrease the use
      of futile life sustaining treatments in the ICU. The author hopes that nurses may
      further expand community hospice care services to help facilitate the peaceful
      dying of terminal patients at home. 

PMID- 25854944
TI  - [The present and future of community/home-based palliative care in Taiwan].
AB  - In Taiwan, the Department of Health (DOH) has implemented regulations and
      policies related to hospice and palliative care since 1995. Taiwan is the first
      country in Asia to have a Natural Death Act, promulgated in 2000. Although
      recognition of the need for palliative care in non-cancer terminally ill patients
      is increasing, at present, the needs of these patients are often not met.
      Moreover, while a majority of the population prefers to die at home, the
      percentage of patients who die in the home setting remains small. The palliative
      care system should be adjusted to improve the accessibility and continuity of
      care based on the needs of patients. Therefore, the Jin-Shan Branch of the
      National Taiwan University Hospital has run a pilot community palliative care
      service model since 2012. National Health Insurance reimbursement was introduced
      in 2014 for community-based palliative care services. Establishing a formal
      system of community-based palliative care should be encouraged in order to
      improve the quality of care at the end of life and to allow more patients to
      receive end-of-life care and die in their own communities. This system will
      require that skilled nurses provide discharge planning, symptoms control, end-of
      life communications, social-resources integration, and social-support networks in
      order to achieve a high quality of end-of-life care. 

PMID- 25854945
TI  - [The perspectives on palliative nursing education].
AB  - The numbers of people who suffer from age-related and chronic diseases have been
      increased worldwide. This has lead to an increased emphasis in the medical
      community on end of life care. This paper references the processes followed
      overseas in developing palliative care education programs as well as the domestic
      experiences promoting the hospitalization, home care, and "share care" models of
      palliative care. Particular emphasis is given to considerations of cultural
      diversity in palliative care. The aim of this paper is to elaborate on the
      prevalent clinical end-of-life care issues that are faced in Taiwan, to cultivate
      core capabilities in end-of-life care, to elicit the current status and
      development of formal nursing education, and to promote continuing education in
      palliative care. Kern formulated a six-step approach to curriculum development in
      education and the details has been discussed . Finally, this paper reflects on
      the current bottlenecks, challenges, and expectations related to palliative care
      curriculum development in order to help medical professionals further put
      humanistic and social care into practice, increase ethical reflection in end of
      life care and nursing competency, and encourage the creation of localized
      textbooks / multimedia e-teaching materials. The fostering of "patient-centered,
      family unit and the social-cultural contexture" for palliative care professionals
      and the ability to respond to the needs of terminal patients and patients with
      chronic diseases are critical to increasing the quality of Taiwan healthcare. 

PMID- 25854946
TI  - [Disorder in life and the world: the illness experiences of women with diabetes
      in Taiwan].
AB  - BACKGROUND: The role of women is strongly associated with health behavior.
      Understanding the illness experiences of women with diabetes helps health
      professionals to provide appropriate health care to women with diabetes. PURPOSE:
      The purpose of this study was to explore the illness experiences of women with
      diabetes. METHODS: This study used interpretive ethnographic methods with in
      depth interviews and field observations to obtain emic points of view from women
      who were diagnosed with diabetes. Agar's hermeneutic cycle was used to analyze
      the collected data. The participants were recruited under the principle of
      maximum variation. The inclusion criteria targeted women who: (1) had been
      diagnosed with diabetes for at least one year, (2) were able to speak Mandarin or
      Taiwanese, and (3) were willing to participate and have their sessions tape
      recorded in a diabetes clinic in southern Taiwan. A total of 18 women with
      diabetes between 24 and 79 years of age were enrolled as participants. RESULTS:
      "Disorder in life and the world" was the main storyline elicited from
      participants. The four themes con-structed from this disorder were: (1) disorder
      of the body: reliance on medical care to understand the body, (2) disorder of
      life: shift from being in control of food to being controlled by food, (3)
      disorder of the family: sick person is perceived as incompetent, and (4) disorder
      of the self: controlling the body for the family. CONCLUSIONS / IMPLICATIONS FOR
      PRACTICE: Healthcare providers should recognize and make positive use of the
      potential of the cultural role of women to improve the ability of women to self
      manage their diabetes. Additionally, perceiving the entire family as the client
      may improve the illness experience for Asian women with diabetes.

PMID- 25854947
TI  - [Application of an improved model of a job-matching platform for nurses].
AB  - BACKGROUND: The three-month attrition rate for new nurses in Taiwan remains high.
      Many hospitals rely on traditional recruitment methods to find new nurses, yet it
      appears that their efficacy is less than ideal. To effectively solve this
      manpower shortage, a nursing resource platform is a project worth developing in
      the future. PURPOSE: This study aimed to utilize a quality-improvement model to
      establish communication between hospitals and nursing students and create a
      customized employee-employer information-matching platform to help nursing
      students enter the workforce. METHODS: This study was structured around a quality
      improvement model and used current situation analysis, literature review, focus
      group discussions, and process re-engineering to formulate necessary content for
      a job-matching platform for nursing. The concept of an academia-industry
      strategic alliance helped connect supply and demand within the same supply chain.
      RESULTS: The nurse job-matching platform created in this study provided job
      flexibility as well as job suitability assessments and continued follow-up and
      services for nurses after entering the workforce to provide more accurate
      matching of employers and employees. CONCLUSIONS: The academia-industry strategic
      alliance, job suitability, and long-term follow-up designed in this study are all
      new features in Taiwan's human resource service systems. The proposed human
      resource process re-engineering provides nursing students facing graduation with
      a professionally managed human resources platform. Allowing students to find an
      appropriate job prior to graduation will improve willingness to work and employee
      retention.

PMID- 25854948
TI  - [Constructing indicators of competence for nurse preceptor instruction skills].
AB  - BACKGROUND: The professional teaching competence of nurse preceptors must be
      monitored regularly. However, the existing instruments that are designed to
      measure nurse preceptor professional teaching competency seldom examine updated
      indicators such as inter-professional practice (IPP) and evidence-based practice.
      PURPOSE: This study constructs indicators for assessing the teaching competence
      of nurse preceptor. METHODS: Phase I used a literature review to identify
      appropriate indicators of nurse preceptor teaching competence. Phase II conducted
      focus-group interviews with 10 nurse preceptors and 6 new nurses from a teaching
      hospital in southern Taiwan. Content analysis was used to construct a preliminary
      framework of indicators. Phase III invited 15 experts to evaluate the content
      validity of the preliminary indicators in two rounds using the Delphi method.
      RESULTS: The teaching-related competence of nurse comprises 36 items in the five
      dimensions of passionate commitment to teaching, harmonious learning atmosphere,
      inductive teaching skills, objective feedback and evaluation, and inter
      professional practice. CONCLUSIONS / IMPLICATIONS FOR PRACTICE: The indicators
      developed in this study may be used by nurse preceptors to examine their teaching
      abilities and by healthcare institutions to design preceptor training curricula.

PMID- 25854949
TI  - [Review and analysis of the review results of Taiwan nurses association nursing
      projects (2011~2013)].
AB  - BACKGROUND: Nursing projects are a key part of N4 professional competency
      training for nursing personnel. Low passage rates for these projects have been
      shown to negatively affect the intent of nursing personnel to advance further in
      the nursing ladder system. PURPOSE: This study analyzes the scores for nursing
      projects between 2011 and 2013, the passage rate for these projects, and the
      differences in passage rates between different types of projects. METHOD: This
      retrospective and descriptive study collected data on nursing projects conducted
      under the auspices of the Taiwan Nurses Association between 2011 and 2013.
      Furthermore, the comments of reviewers on 100 nursing projects were randomly
      selected and subjected to content analysis. RESULTS: A total of 3,359 nursing
      projects were examined. Eliminating unqualified nursing projects left a total of
      3,246 projects for the dataset. A total of 1,099 projects were scored with
      passing grades, giving a passing rate of 33.9%. The authors of these passing
      projects worked primarily in northern Taiwan, worked in medical centers, and
      worked in intensive care departments. The projects submitted by authors in
      central Taiwan had the highest average score and passing rate, while those living
      in offshore islands had the lowest average score and passing rate. Most of the
      project topics belonged to the category: "improvement of nursing service skills
      or quality" (77.3%). Items with the lowest scores were: validation of questions,
      analysis of the current situation, and evaluation of results. The topics of
      nursing projects did not relate significantly to passing rate. However, years of
      experience, geographic location of hospital, level of institution, and department
      each had a statistically significant impact on the passage rate. A content
      analysis of reviewer comments was used to extract common problems. Most of the
      positive comments were related to the category of "literature review and
      reference", while most of the negative comments were related to the categories of
      "literature review and reference", "analysis of current situation", "problem
      result and process", "evaluation of results", and "validation of questions".
      CONCLUSIONS / IMPLICATIONS FOR PRACTICE: This study analyzed the types of nursing
      projects, the trends in submission, and the comments of project reviewers. The
      results indicate that the validation of problems in project writing and current
      situation analysis and the evaluation of results should be improved. These
      findings may be referenced by nursing personnel for executing projects in the
      future and for developing improved criteria / methodologies for the clinical
      ladder system for nursing personnel.

PMID- 25854950
TI  - [An experience applying the teaching strategies of cooperative learning and
      creative thinking in a mental-health nursing practicum for undergraduates at a
      technical college].
AB  - Lack of knowledge and experience is prevalent in undergraduate students who are
      taking their clinical practicum for mental-health nursing. This issue negatively
      affects the learning process. This article shares an experience of implementing a
      practicum-teaching program. This program was developed by the authors to
      facilitate the cooperative learning and clinical care competence of students. A
      series of multidimensional teaching activities was designed by integrating the
      strategies of peer cooperation and creative thinking to promote group and
      individual learning. Results indicate that the program successfully encouraged
      the students to participate more actively in the learning process. Additionally,
      the students demonstrated increased competence in empathetic caring toward
      patients, stronger friendship relationships with peers, and improved self-growth.
      The authors hope this teaching program provides a framework to increase the
      benefits for students of participating in clinical practicums and provides a
      teaching reference for clinical instructors. 

PMID- 25854951
TI  - [Nursing care of chemotherapy-induced peripheral neuropathy].
AB  - Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse event
      occurring in patients who receive neurotoxic chemotherapeutic agents such as
      taxanes, platinum, and vinca alkaloids. The manifestations of CIPN include
      intolerable symmetric numbness, burning and tingling in distal limbs, disruption
      of daily functions, reduced quality of life, and the reduction in dosage or
      discontinued use of these agents. There is a paucity of articles on nursing care
      related to CIPN in the literature. This article reviews the pathophysiology,
      clinical presentation, diagnostic criteria, medical management and nursing care
      of CIPN. Review findings are intended to help nurses identify high-risk groups in
      order to implement preventive measures that strengthen the muscles, train the
      balance, and initiate falling precautions of persons in this population. Timely
      preventive measures may effectively alleviate CIPN symptoms and assure the safety
      and overall quality of life of patients. 

PMID- 25854952
TI  - [Hospital-based psychological first aid provided to patients injured in the
      Lushan earthquake].
AB  - In the aftermath of the 7.0 earthquake that struck Lushan in China's Sichuan
      Province on April 20, 2013, a psychological crisis intervention working group was
      established in a hospital that was treating earthquake victims. Patients at this
      hospital received psychological first aid that was delivered in accordance with
      scientific, systematic, and standardized principles. This first aid employed a
      "rooting mode" methodology and was designed as a supportive psychological
      intervention. Mental assessment results showed that the general mental health,
      acute stress reactions, and anxiety and depression status of all of the 131
      injured who received the psychological intervention had significantly improved (p
      < .05) during the two-week intervention period. This paper introduces the basic
      principles used to develop and provide this first aid, the approach used to
      organize the working groups, the main contents of the intervention, specific
      methods used, and intervention outcomes. This information is provided as a
      reference for providing localized psychological assistance in the aftermath of a
      disaster incident. 

PMID- 25854953
TI  - [The use of therapeutic play in the intensive care of a preschool child with
      virus-associated hemophagocytic syndrome].
AB  - Hospitalization is a stressful experience for children that increases their
      anxiety and fears, generates resistance and noncompliance, and, as a result,
      delays necessary treatments. Developing an age-appropriate intervention to reduce
      the hospitalization-related stress perceived by children is an important
      component of pediatric nursing. This case study used therapeutic play and drawing
      to care for a virus-associated hemophagocytic syndrome preschooler who stayed in
      our pediatric intensive care unit (PICU) between 11/13/2012 and 11/19/2012.
      Stressors faced by the patient included separation from primary caregiver,
      unfamiliarity with the medical environment and equipment, non-comprehension of
      the treatment and medication regimens, and loss of control. The patient displayed
      incorporative behaviors such as crying, screaming, refusing to be touched, and
      requesting parental accompaniment. Painting and picture books were used as
      developmentally appropriate interventions to understand the patient's feelings
      and to provide a means for him to project and release emotions. This strategy
      successfully assisted the child to overcome the perceived stress of
      hospitalization and to cooperate with healthcare providers on his treatment. 

PMID- 25854954
TI  - A nurse-facilitated cognitive behavioural self-management programme for heart
      failure is no more cost effective than usual CBT care.

PMID- 25854955
TI  - In depression, increased psychological reactance is associated with poorer
      treatment compliance.

PMID- 25854956
TI  - Clinically significant pain is experienced by just over a third of all
      hospitalised patients, affecting around a half of surgical and a quarter of
      medical admissions.

PMID- 25854957
TI  - The Child and Family Hospital Experience: Is It Influenced by Family
      Accommodation?
AB  - Patient and family experiences are important indicators of quality of care and
      little is known about how family accommodation affects hospital experience. We
      added questions about accommodation to standardized inpatient pediatric and
      neonatal intensive care unit family experience surveys at 10 U.S. hospitals to
      determine the accommodation types used by families, compare characteristics
      across accommodation types and explore accommodation-type influences on overall
      hospital experience outcomes. Parents of inpatient children (n = 5,105; 93.4%)
      most often stayed in the child's room (76.8%). Parents of neonatal intensive care
      unit infants (n = 362; 6.6%) most often stayed overnight in their own home or
      with relatives/friends (47.2%). Accommodation varied based on hospital, parent,
      and child factors. Accommodation type was a significant predictor for most
      hospital experience outcomes, with families who stayed at a Ronald McDonald House
      reporting more positive overall hospital experiences (odds ratios: ranging from
      1.83 to 4.86 for contrasted accommodation types and three experience outcomes). 

PMID- 25854958
TI  - Economics and Health Reform: Academic Research and Public Policy.
AB  - Two prior studies, conducted in 1966 and in 1979, examined the role of economic
      research in health policy development. Both concluded that health economics had
      not been an important contributor to policy. Passage of the Affordable Care Act
      offers an opportunity to reassess this question. We find that the evolution of
      health economics research has given it an increasingly important role in policy.
      Research in the field has followed three related paths over the past century
      institutionalist research that described problems; theoretical research, which
      proposed relationships that might extend beyond existing institutions; and
      empirical assessments of structural parameters identified in the theoretical
      research. These three strands operating in concert allowed economic research to
      be used to predict the fiscal and coverage consequences of alternative policy
      paths. This ability made economic research a powerful policy force. Key
      conclusions of health economics research are clearly evident in the Affordable
      Care Act. 

PMID- 25854959
TI  - How many nurse practitioners provide primary care? It depends on how you count
      them.
AB  - This study compares different approaches to measuring the number of nurse
      practitioners (NPs) providing primary care services using data from the 2012 U.S.
      National Sample Survey of Nurse Practitioners, North Carolina licensing data from
      2011, and a 2010 California survey of nurse practitioners and nurse midwives.
      Estimates of the number and share of NPs providing primary care depend on how one
      defines primary care. If the definition is based on the field of NP education,
      the estimated shares in primary care specialties are 83.5% in North Carolina and
      90.7% in California; if the definition is based on current or past fields of
      certification, the estimated shares are 79.9% in North Carolina and 74.5%
      nationally. The estimated number is even smaller if one considers employment
      setting (58.4% in North Carolina, 66.8% in California, and 67.8% nationally), and
      shrinks to about half of NPs if focusing on current field of clinical
      specialization. 

PMID- 25854960
TI  - A total internal reflection ellipsometry and atomic force microscopy study of
      interactions between Proteus mirabilis lipopolysaccharides and antibodies.
AB  - Specific antigen-antibody interactions play a central role in the human immune
      system. The objective of this paper is to detect immune complexes using label
      free detection techniques, that is, total internal reflection ellipsometry (TIRE)
      and atomic force microscopy (AFM)-based topography and recognition imaging.
      Interactions of purified rabbit immunoglobulin G (IgG) antibodies with bacterial
      endotoxins (Proteus mirabilis S1959 O3 lipopolysaccharides) were studied.
      Lipopolysaccharide was adsorbed on gold surface for TIRE. In the AFM imaging
      experiments, LPS was attachment to the PEG linker (AFM tip modification). The
      mica surface was covered by IgG. In TIRE, the optical parameters Psi and Delta
      change when a complex is formed. It was found that even highly structured
      molecules, such as IgG antibodies (anti-O3 LPS rabbit serum), preserve their
      specific affinity to their antigens (LPS O3). LPS P. mirabilis O3 response of
      rabbit serum anti-O3 was also tested by topography and recognition imaging. Both
      TIRE and AFM techniques were recruited to check for possible detection of antigen
      antibody recognition event. The presented data allow for determination of
      interactions between a variety of biomolecules. In future research, this
      technique has considerable potential for studying a wide range of antigen
      antibody interactions and its use may be extended to other biomacromolecular
      systems. 

PMID- 25854961
TI  - Engineered Antibody Fragments for Immunodiagnosis of Papaya ringspot virus.
AB  - The present study was undertaken to clone and express the genes encoding antibody
      to the recombinant coat protein (rCP) of Papaya ringspot virus (PRSV) and to
      assess the engineered antibody for the detection of PRSV. A 33-kDa rCP of PRSV,
      which was produced in Escherichia coli, generated PRSV specific antibody in
      immunized mouse. The heavy and light chain variable domain genes (VH and VL) of
      351 and 360 nucleotides, respectively, were cloned from the mRNA isolated from
      the spleen of the immunized mouse with rCP of PRSV. The VH and VL belong to the
      family IgG1 and kappa chain, respectively, and contained the framework regions
      and complementarity determining regions. The VH and VL genes were individually
      used to develop the expression constructs in pET28a (+) vector and 14-kDa
      proteins were obtained in E. coli. The amount of purified VH and VL proteins was
      3-4 mg/l of bacterial culture. Both the antibody fragments recognized PRSV in the
      crude sap; however, the VL antibody fragment showed higher affinity to PRSV. The
      mixture of VH and VL detected PRSV as effectively as polyclonal antibody. The
      recombinant antibody fragments mixture detected PRSV in the field samples with
      100 % accuracy in dot immunobinding assay (DIBA) and enzyme-linked immunosorbent
      assay (ELISA). The sensitivity of the detection of PRSV using antibody fragments
      was 1.0 and 10.0 ng in DIBA and ELISA, respectively. The results showed
      successful isolation of functional single-domain antibody encoding genes to PRSV
      directly from the immunized spleen cells of mouse. This study for the first time
      demonstrates application of bacterial expressed recombinant antibody fragments in
      immunodiagnosis of PRSV.

PMID- 25854962
TI  - The Psychometric Performance of the PROMIS Smoking Assessment Toolkit:
      Comparisons of Real-Data Computer Adaptive Tests, Short Forms, and Mode of
      Administration.
AB  - INTRODUCTION: The PROMIS Smoking Initiative has developed six item banks for
      assessment related to cigarette smoking among adult smokers (Nicotine Dependence,
      Coping Expectancies, Emotional and Sensory Expectancies, Health Expectancies,
      Psychosocial Expectancies, and Social Motivations). This article evaluates the
      psychometric performance of the banks when administered via short form (SF),
      computer adaptive test (CAT), and by mode of administration (computer vs. paper
      and-pencil). METHODS: Data are from two sources: an internet sample (N = 491) of
      daily and nondaily smokers who completed both SFs and CATs via the web and a
      community sample (N = 369) that completed either paper-and-pencil or computer
      administration of the SFs at two time points. First a CAT version of the PROMIS
      Smoking Assessment Toolkit was evaluated by comparing item administration rates
      and scores to the SF administration. Next, we considered the effect of computer
      versus paper-and-pencil administration on scoring and test-retest reliability.
      RESULTS: Across the domains approximately 5.4 to 10.3 items were administered on
      average for the CAT. SF and CAT item response theory-scores were correlated from
      0.82 to 0.92 across the domains. Cronbach's alpha for the four- to eight-item SFs
      among daily smokers ranged from .80 to .91 and .82 to .91 for paper-and-pencil
      and computer administrations, respectively. Test-retest reliability of the SFs
      ranged from 0.79 to 0.89 across mode of administration. CONCLUSIONS: Results
      indicate that the SF and CAT and computer and paper-and-pencil administrations
      provide highly comparable scores for daily and nondaily smokers, but preference
      for SF or CAT administration may vary by smoking domain.

PMID- 25854963
TI  - 'You don't know which bits to believe': qualitative study exploring carers'
      experiences of seeking information on the internet about childhood eczema.
AB  - OBJECTIVE: We sought to explore parents and carers' experiences of searching for
      information about childhood eczema on the internet. DESIGN: A qualitative
      interview study was carried out among carers of children aged 5 years or less
      with a recorded diagnosis of eczema. The main focus of the study was to explore
      carers' beliefs and understandings around eczema and its treatment. As part of
      this, we explored experiences of formal and informal information seeking about
      childhood eczema. Transcripts of interviews were analysed thematically. SETTING:
      Participants were recruited from six general practices in South West England.
      PARTICIPANTS: Interviews were carried out with 31 parents from 28 families.
      RESULTS: Experiences of searching for eczema information on the internet varied
      widely. A few interviewees were able to navigate through the internet and find
      the specific information they were looking for (for instance about treatments
      their child had been prescribed), but more found searching for eczema information
      online to be a bewildering experience. Some could find no information of
      relevance to them, whereas others found the volume of different information
      sources overwhelming. Some said that they were unsure how to evaluate online
      information or that they were wary of commercial interests behind some
      information sources. Interviewees said that they would welcome more signposting
      towards high quality information from their healthcare providers. CONCLUSIONS: We
      found very mixed experiences of seeking eczema information on the internet; but
      many participants in this study found this to be frustrating and confusing.
      Healthcare professionals and healthcare systems have a role to play in helping
      people with long-term health conditions and their carers find reliable online
      information to support them with self-care.

PMID- 25854964
TI  - Prognostic role of the neutrophil-lymphocyte ratio in renal cell carcinoma: a
      meta-analysis.
AB  - OBJECTIVE: Increasing evidence suggests that cancer-associated inflammation is
      associated with poor prognosis in patients with cancer. The role of the
      neutrophil-lymphocyte ratio (NLR) as a predictor in renal cell carcinoma (RCC)
      remains controversial. We conducted the meta-analysis to determine the
      association between NLR and clinical outcome of patients with RCC. METHODS AND
      MATERIALS: Studies were identified from PubMed and EMBASE databases in March
      2014. Meta-analysis was performed to generate combined HRs with 95% CIs for
      overall survival (OS) and recurrence-free/progress-free survival (RFS/PFS).
      RESULTS: 15 cohorts containing 3357 patients were included. Our analysis results
      indicated that elevated NLR predicted poorer OS (HR=1.82, 95% CI 1.51 to 2.19)
      and RFS/PFS (HR=2.18, 95% CI 1.75 to 2.71) in patients with RCC. These findings
      were robust when stratified by study region, sample size, therapeutic
      intervention, types of RCC and study quality. However, it differed significantly
      by assessment of the cut-off value defining 'elevated NLR' in RFS/PFS (p=0.004).
      The heterogeneity in our meta-analysis was mild to moderate. CONCLUSIONS:
      Elevated NLR indicates a poorer prognosis for patients with RCC. NLR should be
      monitored in patients with RCC for rational risk stratification and treatment
      individualisation.

PMID- 25854965
TI  - What the public knows and wants to know about medicines research and development:
      a survey of the general public in six European countries.
AB  - OBJECTIVES: To explore public knowledge of, and interest in, learning more about
      medicines R&D in six European countries. DESIGN: Online survey of 6931 members of
      the public across Europe. METHODS: The survey formed part of a public omnibus
      survey. A quota sampling approach was used with quotas set according to national
      census data on age, gender and government region. The survey explored the
      public's knowledge and awareness of medicines R&D, their interest in learning
      more and the perceived influences on this. RESULTS: The survey was completed by
      6931 members of the public, over 75% of whom reported having no or less than good
      knowledge of medicines R&D. Males were more likely than females to report good
      knowledge (17% vs 15%), and knowledge appeared to decrease with age. Those who
      were currently or had previously been involved in medical research were almost
      five times more likely to report good knowledge of medicines R&D overall (43% vs
      13%). Participants reported good knowledge of medicines safety and clinical
      trials but little knowledge of pharmacoeconomics. They were most interested in
      learning more about medicines safety and personalised and predictive medicine and
      least interested in pharmacoeconomics. Older people, women and respondents with
      current good knowledge of medicines R&D were most interested in learning more
      about medicines R&D. CONCLUSIONS: Experience of medical research appears to play
      a key role in increasing public awareness of and future interest in medicines
      R&D. Some groups may need to be specifically targeted to increase their awareness
      of medicines R&D, for example, women expressed great interest in learning more
      but reported less knowledge than men. It may be useful to explore further the
      views of those who are currently uninterested in learning more.

PMID- 25854966
TI  - Clinical decision-making of cardiologists regarding admission and treatment of
      patients with suspected unstable angina or non-ST-elevation myocardial
      infarction: protocol of a clinical vignette study.
AB  - INTRODUCTION: Cardiologists face the difficult task of rapidly distinguishing
      cardiac-related chest pain from other conditions, and to thoroughly consider
      whether invasive diagnostic procedures or treatments are indicated. The use of
      cardiac risk-scoring instruments has been recommended in international cardiac
      guidelines. However, it is unknown to what degree cardiac risk scores and other
      clinical information influence cardiologists' decision-making. This paper
      describes the development of a binary choice experiment using realistic
      descriptions of clinical cases. The study aims to determine the importance
      cardiologists put on different types of clinical information, including cardiac
      risk scores, when deciding on the management of patients with suspected unstable
      angina or non-ST-elevation myocardial infarction. METHODS AND ANALYSIS:
      Cardiologists were asked, in a nationwide survey, to weigh different clinical
      factors in decision-making regarding patient admission and treatment using
      realistic descriptions of patients in which specific characteristics are varied
      in a systematic way (eg, web-based clinical vignettes). These vignettes represent
      patients with suspected unstable angina or non-ST-elevation myocardial
      infarction. Associations between several clinical characteristics, with
      cardiologists' management decisions, will be analysed using generalised linear
      mixed models. ETHICS AND DISSEMINATION: The study has received ethics approval
      and informed consent will be obtained from all participating cardiologists. The
      results of the study will provide insight into the relative importance of cardiac
      risk scores and other clinical information in cardiac decision-making. Further,
      the results indicate cardiologists' adherence to the European Society of
      Cardiology guideline recommendations. In addition, the detailed description of
      the method of vignette development applied in this study could assist other
      researchers or clinicians in creating future choice experiments.

PMID- 25854967
TI  - Identification of vitamin C transporters in the human airways: a cross-sectional
      in vivo study.
AB  - OBJECTIVES: Vitamin C is an important low-molecular weight antioxidant at the air
      lung interface. Despite its critical role as a sacrificial antioxidant, little is
      known about its transport into the respiratory tract lining fluid (RTLF), or the
      underlying airway epithelial cells. While several vitamin C transporters have
      been identified, such as sodium-ascorbate cotransporters (SVCT1/2) and glucose
      transporters (GLUTs), the latter transporting dehydroascorbate, knowledge of
      their protein distribution within the human lung is limited, in the case of GLUTs
      or unknown for SVCTs. SETTING AND PARTICIPANTS: Protein expression of vitamin C
      transporters (SVCT1/2 and GLUT1-4) was examined by immunohistochemistry in
      endobronchial biopsies, and by FACS in airway leucocytes from lavage fluid,
      obtained from 32 volunteers; 16 healthy and 16 mild asthmatic subjects. In
      addition, antioxidant concentrations were determined in RTLF. The study was
      performed at one Swedish centre. PRIMARY AND SECONDARY OUTCOME MEASURES: The
      primary outcome measure was to establish the location of vitamin C transporters
      in the human airways. As secondary outcome measures, RTLF vitamin C concentration
      was measured and related to transporter expression, as well as bronchial
      epithelial inflammatory and goblet cells numbers. RESULTS: Positive staining was
      identified for SVCT1 and 2 in the vascular endothelium. SVCT2 and GLUT2 were
      present in the apical bronchial epithelium, where SVCT2 staining was
      predominately localised to goblet cells and inversely related to RTLF vitamin C
      concentrations. CONCLUSIONS: This experimental study is the first to demonstrate
      protein expression of GLUT2 and SVCT2 in the human bronchial epithelium. A
      negative correlation between SVCT2-positive goblet cells and bronchial RTLF
      vitamin C concentrations suggests a possible role for goblet cells in regulating
      the extracellular vitamin C pool.

PMID- 25854968
TI  - Respondent-driven sampling to assess mental health outcomes, stigma and
      acceptance among women raising children born from sexual violence-related
      pregnancies in eastern Democratic Republic of Congo.
AB  - OBJECTIVES: Assess mental health outcomes among women raising children from
      sexual violence-related pregnancies (SVRPs) in eastern Democratic Republic of
      Congo and stigma toward and acceptance of women and their children. DESIGN:
      Participants were recruited using respondent-driven sampling. SETTING: Bukavu,
      Democratic Republic of Congo in 2012. PARTICIPANTS: 757 adult women raising
      children from SVRPs were interviewed. A woman aged 18 and older was eligible for
      the study if she self-identified as a sexual violence survivor since the start of
      the conflict (~1996), conceived an SVRP, delivered a liveborn child and was
      currently raising the child. A woman was ineligible for the study if the SVRP
      ended with a spontaneous abortion or fetal demise or the child was not currently
      living or in the care of the biological mother. INTERVENTION: Trained female
      Congolese interviewers verbally administered a quantitative survey after
      obtaining verbal informed consent. OUTCOME MEASURES: Symptom criteria for major
      depressive disorder, post-traumatic stress disorder, anxiety and suicidality were
      assessed, as well as stigma toward the woman and her child. Acceptance of the
      woman and child from the spouse, family and community were analysed. RESULTS:
      48.6% met symptom criteria for major depressive disorder, 57.9% for post
      traumatic stress disorder, 43.3% for anxiety and 34.2% reported suicidality.
      Women who reported stigma from the community (38.4%) or who reported stigma
      toward the child from the spouse (42.9%), family (31.8%) or community (38.1%)
      were significantly more likely to meet symptom criteria for most mental health
      disorders. Although not statistically significant, participants who reported
      acceptance and acceptance of their children from the spouse, family and community
      were less likely to meet symptom criteria. CONCLUSIONS: Women raising children
      from SVRPs experience symptoms of mental health disorders. Programming addressing
      stigma and acceptance following sexual violence may improve mental health
      outcomes in this population.

PMID- 25854969
TI  - Associations between pentraxin 3 and severity of coronary artery disease.
AB  - OBJECTIVE: To investigate the associations between plasma levels of pentraxins 3
      (PTX3) and C reactive protein (CRP) and the severity of coronary artery lesions.
      DESIGN AND METHODS: 60 patients with coronary heart disease (CHD) who underwent
      coronary angiography (CAG) in our hospital were included. Plasma was collected
      during CAG. The coronary Gensini score was used to evaluate the severity of
      coronary artery lesions. Associations between Gensini scores and plasma levels of
      PTX3 and CRP were analysed. Patients with estimated glomerular filtration rate
      <60 mL/min/1.73 m(2) were included in the chronic renal dysfunction subgroup.
      RESULTS: A linear correlation was observed between PTX3 and the Gensini score
      (r=0.513, p<0.001). One-way analysis of variance showed that PTX3 levels were
      significantly higher in patients with Gensini scores >90 compared with patients
      with scores of 46-90 or <45 (0-45:4.8+/-0.8, 46-90:6.7+/-1.2, >90:7.7+/-2.0,
      p<0.001). Stepwise multiple linear regression showed that PTX3 levels were
      significantly associated with Gensini score in patients with chronic renal
      dysfunction (p=0.012), while no significant association was found for CRP.
      CONCLUSIONS: PTX3 levers were positively associated with the severity of coronary
      artery lesions. PTX3 is closely associated with the severity of coronary artery
      stenosis in patients with chronic renal dysfunction.

PMID- 25854970
TI  - Description and preliminary results from a structured specialist behavioural
      weight management group intervention: Specialist Lifestyle Management (SLiM)
      programme.
AB  - BACKGROUND: Specialist Lifestyle Management (SLiM) is a structured patient
      education and self-management group weight management programme. Each session is
      run monthly over a 6-month period providing a less intensive long-term approach.
      The groups are patient-centred incorporating educational, motivational,
      behavioural and cognitive elements. The theoretical background, programme
      structure and preliminary results of SLiM are presented. SUBJECTS/METHODS: The
      study was a pragmatic service evaluation of obese patients with a body mass index
      (BMI) >=35 kg/m(2) with comorbidity or >=40 kg/m(2) without comorbidity referred
      to a specialist weight management service in the West Midlands, UK. 828 patients
      were enrolled within SLiM over a 48-month period. Trained facilitators delivered
      the programme. Preliminary anonymised data were analysed using the intention-to
      treat principle. The primary outcome measure was weight loss at 3 and 6 months
      with comparisons between completers and non-completers performed. The last
      observation carried forward was used for missing data. RESULTS: Of the 828
      enrolled within SLiM, 464 completed the programme (56%). The mean baseline weight
      was 135 kg (BMI=49.1 kg/m(2)) with 87.2% of patients having a BMI>=40 kg/m(2) and
      12.4% with BMI>=60 kg/m(2). The mean weight change of all patients enrolled was 
      4.1 kg (95% CI -3.6 to -4.6 kg, p=0.0001) at the end of SLiM, with completers
      (n=464) achieving -5.5 kg (95% CI -4.2 to -6.2 kg, p=0.0001) and non-completers
      achieving -2.3 kg (p=0.0001). The majority (78.6%) who attended the 6-month
      programme achieved weight loss with 32.3% achieving a >=5% weight loss.
      CONCLUSIONS: The SLiM programme is an effective group intervention for the
      management of severe and complex obesity.

PMID- 25854971
TI  - Hydrogen sulfide and traffic-related air pollutants in association with increased
      mortality: a case-crossover study in Reykjavik, Iceland.
AB  - OBJECTIVES: To study the association between daily mortality and short-term
      increases in air pollutants, both traffic-related and the geothermal source
      specific hydrogen sulfide (H2S). DESIGN: Population-based, time stratified case
      crossover. A lag time to 4 days was considered. Seasonal, gender and age
      stratification were calculated. Also, the best-fit lag when introducing H2S >7
      ug/m(3) was selected by the Akaike Information Criterion (AIC). SETTING: The
      population of the greater Reykjavik area (n=181,558) during 2003-2009.
      PARTICIPANTS: Cases were defined as individuals living in the Reykjavik capital
      area, 18 years or older (N=138,657), who died due to all natural causes (ICD-10
      codes A00-R99) other than injury, poisoning and certain other consequences of
      external causes, or cardiovascular disease (ICD-10 codes I00-I99) during the
      study period. MAIN OUTCOME MEASURE: Percentage increases in risk of death (IR%)
      following an interquartile range increase in pollutants. RESULTS: The total
      number of deaths due to all natural causes was 7679 and due to cardiovascular
      diseases was 3033. The interquartile range increased concentrations of H2S (2.6
      ug/m(3)) were associated with daily all natural cause mortality in the Reykjavik
      capital area. The IR% was statistically significant during the summer season (lag
      1: IR%=5.05, 95% CI 0.61 to 9.68; lag 2: IR%=5.09, 95% CI 0.44 to 9.97), among
      males (lag 0: IR%=2.26, 95% CI 0.23 to 4.44), and among the elderly (lag 0:
      IR%=1.94, 95% CI 0.12 to 1.04; lag 1: IR%=1.99, 95% CI 0.21 to 1.04), when
      adjusted for traffic-related pollutants and meteorological variables. The traffic
      related pollutants were generally not associated with statistical significant
      IR%s. CONCLUSIONS: The results suggest that ambient H2S air pollution may
      increase mortality in Reykjavik, Iceland. To the best of our knowledge, ambient
      H2S exposure has not previously been associated with increased mortality in
      population-based studies and therefore the results should be interpreted with
      caution. Further studies are warranted to confirm or refute whether H2S exposure
      induces premature deaths.

PMID- 25854972
TI  - A cost-benefit analysis of twice-daily consultant ward rounds and clinical input
      on investigation and pharmacy costs in a major teaching hospital in the UK.
AB  - OBJECTIVES: Misuse of investigations, medications and hospital beds is costing
      the National Health Service (NHS) billions of pounds with little evidence that
      approaches centred on reducing overuse are sustainable. Our previous study
      demonstrated that twice-daily consultant ward rounds reduce inpatient length of
      stay and suggested a reduction in overuse of investigations and medications. This
      study aims to assess the impact of daily consultant ward rounds on the use of
      investigations and medications and estimate the potential cost benefit. SETTINGS:
      The study was performed on two medical wards in a major city university teaching
      hospital in Liverpool, UK, receiving acute admissions from medical assessment and
      emergency departments. PARTICIPANTS AND INTERVENTION: The total number of
      patients admitted, investigations performed and pharmacy costs incurred were
      collected for 2 years before and following a change in the working practice of
      consultants from twice-weekly to twice-daily consultant ward rounds on the two
      medical wards. OUTCOME MEASURES: We performed a cost-benefit analysis to assess
      the net amount of money saved by reducing inappropriate investigations and
      pharmacy drug use following the intervention. RESULTS: Despite a 70% increase in
      patient throughput (p<0.01) the investigations and pharmacy, costs per patient
      reduced by 50% over a 12-month period (p<0.01) and were sustained for the next 12
      months. The reduction in investigations and medication use did not have any
      effect on the readmission or mortality rate (p=NS), whereas, the length of stay
      was almost halved (p<0.01). Daily senior clinician input resulted in a net cost
      saving of L336,528 per year following the intervention. CONCLUSIONS: Daily
      consultant input has a significant impact on reducing the inappropriate use of
      investigations and pharmacy costs saving the NHS more than L650K on the two wards
      over a 2-year period.

PMID- 25854973
TI  - Systematic review: unmet supportive care needs in people diagnosed with chronic
      liver disease.
AB  - OBJECTIVE: People with chronic liver disease, particularly those with
      decompensated cirrhosis, experience several potentially debilitating
      complications that can have a significant impact on activities of daily living
      and quality of life. These impairments combined with the associated complex
      treatment mean that they are faced with specific and high levels of supportive
      care needs. We aimed to review reported perspectives, experiences and concerns of
      people with chronic liver disease worldwide. This information is necessary to
      guide development of policies around supportive needs screening tools and to
      enable prioritisation of support services for these patients. DESIGN: Systematic
      searches of PubMed, MEDLINE, CINAHL and PsycINFO from the earliest records until
      19 September 2014. Data were extracted using standardised forms. A qualitative,
      descriptive approach was utilised to analyse and synthesise data. RESULTS: The
      initial search yielded 2598 reports: 26 studies reporting supportive care needs
      among patients with chronic liver disease were included, but few of them were
      patient-reported needs, none used a validated liver disease-specific supportive
      care need assessment instrument, and only three included patients with cirrhosis.
      Five key domains of supportive care needs were identified: informational or
      educational (eg, educational material, educational sessions), practical (eg,
      daily living), physical (eg, controlling pruritus and fatigue), patient care and
      support (eg, support groups), and psychological (eg, anxiety, sadness).
      CONCLUSIONS: While several key domains of supportive care needs were identified,
      most studies included hepatitis patients. There is a paucity of literature
      describing the supportive care needs of the chronic liver disease population
      likely to have the most needs--namely those with cirrhosis. Assessing the
      supportive care needs of people with chronic liver disease have potential utility
      in clinical practice for facilitating timely referrals to support services.

PMID- 25854974
TI  - Secondhand smoke in outdoor settings: smokers' consumption, non-smokers'
      perceptions, and attitudes towards smoke-free legislation in Spain.
AB  - OBJECTIVE: To describe where smokers smoke outdoors, where non-smokers are
      exposed outdoors to secondhand smoke (SHS), and attitudes towards smoke-free
      outdoor areas after the implementation of national smoke-free legislation.
      DESIGN: This cross-sectional study was conducted between June 2011 and March 2012
      (n=1307 participants). SETTING: Barcelona, Spain. PARTICIPANTS: Representative,
      random sample of the adult (>=16 years) population. PRIMARY AND SECONDARY
      OUTCOMES: Proportion of smoking and prevalence of exposure to SHS in the various
      settings according to type of enclosure. Percentages of support for outdoor smoke
      free policies according to smoking status. RESULTS: Smokers reported smoking
      outdoors most in bars and restaurants (54.8%), followed by outdoor places at work
      (46.8%). According to non-smokers, outdoor SHS exposure was highest at home
      (42.5%) and in bars and restaurants (33.5%). Among non-smoking adult students,
      90% claimed exposure to SHS on university campuses. There was great support for
      banning smoking in the majority of outdoor areas, which was stronger among non
      smokers than smokers. Over 70% of participants supported smoke-free playgrounds,
      school and high school courtyards, and the grounds of healthcare centres.
      CONCLUSIONS: Extending smoking bans to selected outdoor settings should be
      considered in further tobacco control interventions to protect non-smokers from
      SHS exposure and to establish a positive model for youth. The majority of public
      support for some outdoor smoke-free areas suggests that it is feasible to extend
      smoking bans to additional outdoor settings.

PMID- 25854975
TI  - A cross sectional study of surgical training among United Kingdom general
      practitioners with specialist interests in surgery.
AB  - OBJECTIVES: Increasing numbers of minor surgical procedures are being performed
      in the community. In the UK, general practitioners (family medicine physicians)
      with a specialist interest (GPwSI) in surgery frequently undertake them. This
      shift has caused decreases in available cases for junior surgeons to gain and
      consolidate operative skills. This study evaluated GPwSI's case-load, procedural
      training and perceptions of offering formalised operative training experience to
      surgical trainees. DESIGN: Prospective, questionnaire-based cross-sectional
      study. SETTING/PARTICIPANTS: A novel, 13-item, self-administered questionnaire
      was distributed to members of the Association of Surgeons in Primary Care (ASPC).
      A total 113 of 120 ASPC members completed the questionnaire, representing a 94%
      response rate. Respondents were general practitioners practising or intending to
      practice surgery in the community. RESULTS: Respondents performed a mean of 38
      (range 5-150) surgical procedures per month in primary care. 37% (42/113) of
      respondents had previously been awarded Membership or Fellowship of a Surgical
      Royal College; 22% (25/113) had completed a surgical certificate or diploma or
      undertaken a course of less than 1 year duration. 41% (46/113) had no formal
      British surgical qualifications. All respondents believed that surgical training
      in primary care could be valuable for surgical trainees, and the majority
      (71/113, 63%) felt that both general practice and surgical trainees could benefit
      equally from such training. CONCLUSIONS: There is a significant volume of
      surgical procedures being undertaken in the community by general practitioners,
      with the capacity and appetite for training of prospective surgeons in this
      setting, providing appropriate standards are achieved and maintained,
      commensurate with current standards in secondary care. Surgical experience and
      training of GPwSI's in surgery is highly varied, and does not yet benefit from
      the quality assurance secondary care surgical training in the UK undergoes. The
      Royal Colleges of Surgery and General Practice are well placed to invest in such
      infrastructure to provide long-term, high-quality service and training in the
      community.

PMID- 25854976
TI  - CareTrack Kids-part 1. Assessing the appropriateness of healthcare delivered to
      Australian children: study protocol for clinical indicator development.
AB  - INTRODUCTION: Despite the widespread availability of clinical guidelines,
      considerable gaps remain between the care that is recommended (appropriate care)
      and the care provided. This protocol describes a research methodology to develop
      clinical indicators for appropriate care for common paediatric conditions.
      METHODS AND ANALYSIS: We will identify conditions amenable to population-level
      appropriateness of care research and develop clinical indicators for each
      condition. Candidate conditions have been identified from published research;
      burden of disease, prevalence and frequency of presentation data; and quality of
      care priority lists. Clinical indicators will be developed through searches of
      national and international guidelines, and formatted with explicit criteria for
      inclusion, exclusion, time frame and setting. Experts will review the indicators
      using a wiki-based approach and modified Delphi process. A formative evaluation
      of the wiki process will be undertaken. ETHICS AND DISSEMINATION: Human Research
      Ethics Committee approvals have been received from Sydney Children's Hospital
      Network, Children's Health Queensland Hospital and Health Service, and the
      Women's and Children's Health Network (South Australia). Applications are under
      review with Macquarie University and the Royal Australian College of General
      Practitioners. We will submit the results of the study to relevant journals and
      offer national and international presentations.

PMID- 25854977
TI  - CareTrack Kids-part 2. Assessing the appropriateness of the healthcare delivered
      to Australian children: study protocol for a retrospective medical record review.
AB  - INTRODUCTION: Australian and international clinical practice guidelines are
      available for common paediatric conditions. Yet there is evidence that there are
      substantial variations between the guidelines, recommendations (appropriate care)
      and the care delivered. This paper describes a study protocol to determine the
      appropriateness of the healthcare delivered to Australian children for 16 common
      paediatric conditions in acute and primary healthcare settings. METHODS AND
      ANALYSIS: A random sample of 6000-8000 medical records representing a cross
      section of the Australian paediatric population will be reviewed for
      appropriateness of care against a set of indicators within three Australian
      states (New South Wales, Queensland and South Australia) using multistage,
      stratified sampling. Medical records of children aged <16 years who presented
      with at least one of the study conditions during 2012 and 2013 will be reviewed.
      ETHICS AND DISSEMINATION: Human Research Ethics Committee approvals have been
      received from the Sydney Children's Hospital Network, Children's Health
      Queensland Hospital and Health Service and Women's and Children's Hospital
      Network (South Australia). An application is under review for the Royal
      Australian College of General Practitioners. The authors will submit the results
      of the study to relevant journals and offer oral presentations to researchers,
      clinicians and policymakers at national and international conferences.

PMID- 25854978
TI  - CareTrack Kids-part 3. Adverse events in children's healthcare in Australia:
      study protocol for a retrospective medical record review.
AB  - INTRODUCTION: A high-quality health system should deliver care that is free from
      harm. Few large-scale studies of adverse events have been undertaken in
      children's healthcare internationally, and none in Australia. The aim of this
      study is to measure the frequency and types of adverse events encountered in
      Australian paediatric care in a range of healthcare settings. METHODS AND
      ANALYSIS: A form of retrospective medical record review, the Institute of
      Healthcare Improvement's Global Trigger Tool, will be modified to collect data.
      Records of children aged <16 years managed during 2012 and 2013 will be reviewed.
      We aim to review 6000-8000 records from a sample of healthcare practices
      (hospitals, general practices and specialists). ETHICS AND DISSEMINATION: Human
      Research Ethics Committee approvals have been received from the Sydney Children's
      Hospital Network, Children's Health Queensland Hospital and Health Service, and
      the Women's and Children's Hospital Network in South Australia. An application is
      under review with the Royal Australian College of General Practitioners. The
      authors will submit the results of the study to relevant journals and undertake
      national and international oral presentations to researchers, clinicians and
      policymakers.

PMID- 25854980
TI  - A Classification of Healthcare Facilities: Toward the Development of Energy
      Performance Benchmarks for Day Surgery Centers in Australia.
AB  - OBJECTIVE: In the literature, there is no consistent classification of healthcare
      facilities. In order to benchmark, assess, and compare the environmental
      performance of these buildings, it is important to clearly identify the typology
      within the scope of a particular research. This article identifies the different
      typologies within the healthcare sector, particularly in Australia, with the aim
      of the development of energy performance benchmarks for day surgery/procedure
      centers. BACKGROUND: Healthcare buildings encompass a wide range of facilities.
      They all share the same purpose of healing and offering a health service for
      patients. However, they vary significantly in terms of patient type and service
      provided. These buildings consume a considerable amount of energy, and as a
      result of the different designs and sizes, their pattern of energy consumption
      varies. METHODS: The research used a systematic review of the literature to
      determine how the term "healthcare facility" has been employed in different
      contexts. In order to better understand the differences in healthcare facilities,
      definitions and the origin of hospitals and healthcare facilities are introduced
      and a framework for the classification of healthcare facilities and hospitals is
      proposed. RESULTS: Healthcare facilities are classified into the following six
      categories: patient type, care provided, management and ownership, level of care,
      facility size, and location. Based on these classifications, a categorization for
      the studies of energy performance in healthcare is introduced. CONCLUSIONS: This
      study provides a basis for assessment and comparison for a particular healthcare
      building typology that will assist researchers working in the field of design and
      energy assessment of healthcare facilities.

PMID- 25854979
TI  - What matters to patients? A systematic review of preferences for medication
      associated outcomes in mental disorders.
AB  - OBJECTIVE: To investigate patients' preferences for outcomes associated with
      psychoactive medications. SETTING/DESIGN: Systematic review of stated preference
      studies. No settings restrictions were applied. PARTICIPANTS/ELIGIBILITY
      CRITERIA: We included studies containing quantitative data regarding the relative
      value adults with mental disorders place on treatment outcomes. Studies with high
      risk of bias were excluded. PRIMARY AND SECONDARY OUTCOME MEASURES: We restricted
      the scope of our review to preferences for outcomes, including the consequences
      from, attributes of, and health states associated with particular medications or
      medication classes, and process outcomes. RESULTS: After reviewing 11 215
      citations, 16 studies were included in the systematic review. These studies
      reported the stated preferences from patients with schizophrenia (n=9),
      depression (n=4), bipolar disorder (n=2) and attention deficit hyperactive
      disorder (n=1). The median sample size was 81. Side effects and symptom outcomes
      outnumbered functioning and process outcomes. Severe disease and hospitalisation
      were reported to be least desirable. Patients with schizophrenia tended to value
      disease states as higher and side effects as lower, compared to other stakeholder
      groups. In depression, the ability to cope with activities was found to be more
      important than a depressed mood, per se. Patient preferences could not
      consistently be predicted from demographic or disease variables. Only a limited
      number of potentially important outcomes had been investigated. Benefits to
      patients were not part of the purpose in 9 of the 16 studies, and in 10 studies
      patients were not involved when the outcomes to present were selected.
      CONCLUSIONS: Insufficient evidence exists on the relative value patients with
      mental disorders place on medication-associated outcomes. To increase patient
      centredness in decisions involving psychoactive drugs, further research-with
      outcomes elicited from patients, and for a larger number of conditions-should be
      undertaken. TRIAL REGISTRATION NUMBER: PROSPERO CRD42013005685.

PMID- 25854982
TI  - Giant cystic schwannoma of the middle mediastinum with cervical extension.
AB  - Schwannomas (neurilemmomas) are benign tumors arising from the Schwann cells of
      the neural sheath. They are typically, well-encapsulated lesions which rarely
      adhere to the adjacent structures. In the chest, schwannomas are often seen
      within the posterior mediastinum and commonly originating along intercostal
      nerves. Several operative approaches have previously been described for the
      resection of these tumors, including thoracoscopic techniques and posterolateral
      thoracotomy. We report in this case a giant cystic mediastinal schwannoma of the
      left recurrent laryngeal nerve with cervical extension, unresectable by the usual
      described approaches, which was completely removed through a cervical approach. 

PMID- 25854984
TI  - Function of MsiR on canavanine-mediated repression in Mesorhizobium tianshanense.
AB  - Mesorhizobium tianshanense employs MsiA as canavanine exporter, which is
      upregulated by MsiR, to successfully form a symbiosis with the legume Glycyrrhiza
      uralensis. In this research, through gel-shift and bacterial two-hybrid
      examination, MsiR was found to spontaneously form dimers and bind to msiA
      promoter without additional canavanine. Six truncated forms of MsiR were
      constructed, and the conserved helix-turn-helix (HTH), substrate-binding, and
      surface-loop domains were found essential for MsiR functions. Random mutagenesis
      was used to study the functional sites of MsiR. Seven point mutants were
      selected, in which three mutants constitutively induced msiA expression without
      additional canavanine, two mutants partially changed substrate specificity, and
      the other two were almost null mutants. Results from the site mutation show that
      the functional subunits (HTH domain, dimerization interface domains, and C
      terminal) are important in the conformation and induction ability of MsiR. 

PMID- 25854985
TI  - Late breaking trials of 2014 in coronary artery disease: Commentary covering ACC,
      EuroPCR, SCAI, TCT, ESC, and AHA.
AB  - With the plethora of clinical trials, it is difficult for busy interventional
      cardiologists to stay up to date. Therefore, the SCAI Publications Committee
      concisely summarizes and provides editorial commentary on the most important
      coronary trials from the large international meetings of 2014. The intent is to
      allow quick assimilation of trial results into interventional practice.

PMID- 25854986
TI  - Pharmacokinetic (PK) drug interaction studies of cabozantinib: Effect of CYP3A
      inducer rifampin and inhibitor ketoconazole on cabozantinib plasma PK and effect
      of cabozantinib on CYP2C8 probe substrate rosiglitazone plasma PK.
AB  - Cabozantinib is a small-molecule tyrosine kinase inhibitor that has been approved
      for the treatment of patients with progressive, metastatic medullary thyroid
      cancer. In vitro data indicate that (1) cytochrome P450 (CYP) 3A4 is the primary
      CYP isoenzyme involved in the metabolism of cabozantinib, and (2) CYP2C8 is the
      CYP isoenzyme most potently inhibited by cabozantinib with potential for in vivo
      inhibition at clinically relevant plasma exposures. Pharmacokinetic (PK) drug
      drug interactions (DDIs) were evaluated clinically between cabozantinib and (1) a
      CYP3A inducer (rifampin) in healthy volunteers, (2) a CYP3A inhibitor
      (ketoconazole) in healthy volunteers, and (3) a CYP2C8 substrate (rosiglitazone)
      in patients with solid tumors. Compared with cabozantinib given alone,
      coadministration with rifampin resulted in a 4.3-fold higher plasma clearance
      (CL/F) of cabozantinib and a 77% decrease in cabozantinib plasma AUC0-inf ,
      whereas coadministration with ketoconazole decreased cabozantinib CL/F by 29% and
      increased cabozantinib AUC0-inf by 38%. Chronic coadministration with
      cabozantinib resulted in no significant effect on rosiglitazone plasma Cmax ,
      AUC0-24 , or AUC0-inf . In summary, chronic use of strong CYP3A inducers and
      inhibitors should be avoided when cabozantinib is administered, and cabozantinib
      at clinically relevant exposures is not anticipated to markedly affect the PK of
      concomitant medications via CYP enzyme inhibition. 

PMID- 25854987
TI  - The impact of angiotensin receptor blockers on arterial stiffness: a meta
      analysis.
AB  - Some studies reported a protective role of angiotensin receptor blockers (ARBs)
      against arterial stiffness. Therefore, we performed a meta-analysis of published
      clinical trials to systematically assess the impact of ARBs on arterial stiffness
      as measured by using pulse wave velocity (PWV). Eligible articles were identified
      by searching PubMed, EMBASE, Cochrane, Wanfang and CNKI databanks before 31 July
      2014. The data were extracted independently and in duplicate. Forty articles
      including 53 clinical trials qualified, including 1650 and 1659 subjects in ARB
      treatment and control groups, respectively. Overall reductions in carotid-femoral
      PWV (cfPWV) and brachial-ankle PWV (baPWV) were statistically significant, with
      an average of -42.52 cm s(-1) (95% CI: -81.82 to -3.21; P=0.034) and -107.08 cm
      s(-1) (95% CI: -133.98 to -80.18; P<0.0005), respectively, after receiving ARBs.
      Subgroup analysis by ARB type revealed that telmisartan (weighted mean difference
      or WMD=-100.82 cm s(-1); P<0.0005) and valsartan (WMD=-104.59 cm s(-1); P<0.0005)
      significantly reduced baPWV, but only valsartan reduced cfPWV (WMD=-65.58;
      P=0.030). cfPWV was significantly reduced in comparisons of ARBs with placebo
      (WMD=-79.65 cm s(-1); P=0.001), and baPWV was significantly reduced with calcium
      channel blockers (WMD=-130.74 cm s(-1); P<0.0005). There were low probabilities
      of publication bias. Taken together, our findings support the important role of
      ARB treatment in improving arterial stiffness. 

PMID- 25854988
TI  - Impact of the augmentation time ratio on direct measurement of central aortic
      pressure in the presence of coronary artery disease.
AB  - The augmentation index measured by using the central artery pressure is
      associated with an increased risk of coronary artery disease (CAD). However, no
      study has examined the role of the time duration of the central artery pressure
      on CAD. Therefore, we evaluated the relationship between the central blood
      pressure time duration and the presence of CAD. All patients without a history of
      revascularization or prior myocardial infarction who underwent an elective
      coronary angiography at one of the two hospitals from January to September 2013
      were analyzed. CAD was defined as a significant stenosis in one of the main
      coronary branches. The augmentation time ratio was defined as the ratio of the
      reflection to peak systolic time T2T1 duration divided by the peak systolic time
      to aortic notch T3T2 duration. We analyzed the relationship between the central
      pressure waveform (not only augmentation pressure) and the presence of CAD. A
      total of 146 (57.3%) out of 255 patients had a significant CAD. T2T1 duration was
      longer in the CAD group than the no CAD group, and the T3T2 duration was shorter
      in the CAD group than the no CAD group. The augmentation time ratio (T2T1/T3T2)
      was significantly larger in the CAD group than in the no CAD group. The
      augmentation index and augmentation pressure were lower in the no CAD group, but
      this difference was not statistically significant. The augmentation time ratio
      was an independent factor related to no CAD, especially in patients with a high
      augmentation index (odds ratio, 2.17; 95% confidence interval, 1.02-4.63). The
      augmentation time ratio was an independent factor related to the presence of CAD.

PMID- 25854991
TI  - The influence of socioeconomic status on patient survival on chronic dialysis.
AB  - Socioeconomic status (SES) has been linked to worse end-stage kidney disease
      survival. The effect of SES on survival on chronic dialysis, including the impact
      of transplantation, was examined. A retrospective, observational study
      investigated the association of SES with dialysis patient survival, with
      censoring at time of transplantation. Adult patients commencing dialysis from
      1990 to 2009 in an Irish tertiary center received a spatial SES score using the
      2011 Pobal Haase-Pratschke Deprivation Index and were compared by quartile. Cox
      proportional hazard models and Kaplan-Meier survival analysis examined any
      association of SES with survival. The 1794 patients included had a median follow
      up of 3.8 years. Patients in the lowest SES area quartile were significantly
      younger than the highest, mean age 56.7 vs. 59 years, P = 0.006, respectively.
      There was no association between SES area score and survival in an unadjusted
      model (hazard ratio [HR] 1.00, 95% confidence interval [CI] 0.99-1.01). Survival
      in the highest SES area quartile was superior to the lowest SES in a
      multivariable adjusted model including age, gender, and dialysis modality (HR
      0.83, 95% CI 0.70-0.99, P = 0.04). These results were only mildly attenuated by
      censoring at time of transplantation (highest SES area quartile deprived vs.
      lowest SES area quartile, HR 0.85, 95% CI 0.70-1.03, P = 0.09). Superior patient
      survival was identified in the highest SES areas compared with the lowest
      following age-adjusted analyses, despite the older population in the most
      affluent areas. Further research should focus on identifying modifiable targets
      for intervention that account for this socioeconomic-related survival advantage. 

PMID- 25854990
TI  - TLR4 is a critical regulator of angiotensin II-induced vascular remodeling: the
      roles of extracellular SOD and NADPH oxidase.
AB  - Toll-like receptor 4 (TLR4) and angiotensin II (AngII) induce vascular remodeling
      through the production of reactive oxygen species (ROS). AngII has also been
      shown to increase antioxidant enzyme extracellular superoxide dismutase (ecSOD).
      However, the roles of TLR4 in Ang II-induced ROS production, vascular remodeling
      and hypertension remain unknown. Mice lacking TLR4 function showed significant
      inhibition of vascular remodeling in response to chronic AngII infusion, with no
      impact on blood pressure. The increases in ROS level and NADPH oxidase activity
      in response to AngII infusion were markedly blunted in TLR4-deficient mice.
      Similar effects were observed in wild-type (WT) mice treated with a sub-depressor
      dose of the AT1 receptor antagonist irbesartan, which had no effects on TLR4
      deficient mice. Intriguingly, the AngII infusion-induced increases in ecSOD
      activity and expression were rather enhanced in TLR4-deficient mice compared with
      WT mice, whereas the expression of the proinflammatory chemokine MCP-1 was
      decreased. Importantly, AngII-induced vascular remodeling was positively
      correlated with NADPH oxidase activity, ROS levels and MCP-1 expression levels.
      Notably, chronic norepinephrine infusion, which elevates blood pressure without
      increasing ROS production, did not induce significant vascular remodeling in WT
      mice. Taken together, these findings suggest that ROS elevation is required for
      accelerating vascular remodeling but not for hypertensive effects in this model.
      We demonstrated that TLR4 plays a pivotal role in regulating AngII-induced
      vascular ROS levels by inhibiting the expression and activity of the antioxidant
      enzyme ecSOD, as well as by activating NADPH oxidase, which enhances inflammation
      to facilitate the progression of vascular remodeling. 

PMID- 25854989
TI  - Blood pressure decrease in spontaneously hypertensive rats folowing renal
      denervation or dopamine beta-hydroxylase inhibition with etamicastat.
AB  - Overactivity of the sympathetic nervous system has an important role in the
      development and progression of arterial hypertension. Catheter-based renal nerve
      ablation for the treatment of drug-resistant hypertension has recently been
      developed. An alternative strategy for the modulation of sympathetic nerve
      function is to reduce the biosynthesis of noradrenaline (NA) by inhibiting
      dopamine beta-hydroxylase (DbetaH), the enzyme that catalyzes the conversion of
      dopamine (DA) to NA in the sympathetic nerves. Renal denervation (RDN) surgery
      was performed in spontaneously hypertensive rats (SHR) to evaluate the effect of
      RDN on the DA and NA levels and on blood pressure over a 28-day period. The
      selective peripheral DbetaH inhibitor etamicastat (30 mg kg (-1)day(-1)) was
      administered to another cohort of SHR. RDN and etamicastat treatment had no
      effect on the renal function, as assessed by measuring the water balance
      response, renal function and urinary electrolyte levels. RDN significantly
      decreased the systolic blood pressure (SBP) and the diastolic blood pressure
      (DBP). A gradual return of the SBP and the DBP to the high baseline levels was
      observed over time. Conversely, treatment with etamicastat resulted in a
      significant decrease in the SBP and the DBP at all time points. On the last day
      of the assessment, NA levels in renal tissue were significantly decreased in both
      RDN and etamicastat-treated groups. In contrast, the NA levels in the left
      ventricle were decreased only in the etamicastat-treated group. Thus, RDN
      produces transitory decreases in blood pressure, whereas prolonged downregulation
      of sympathetic drive with the DbetaH inhibitor etamicastat results in a sustained
      decrease in the SBP and the DBP.

PMID- 25854992
TI  - Cloning, purification and evaluation of the enzymatic properties of a novel
      arylacetonitrilase from Luminiphilus syltensis NOR5-1B: a potential biocatalyst
      for the synthesis of mandelic acid and its derivatives.
AB  - OBJECTIVE: To examine nitrilase-mediated hydrolysis of nitriles to produce
      optically pure alpha-hydroxycarboxylic acids. RESULTS: A novel nitrilase,
      GPnor51, from Luminiphilus syltensis NOR5-1B was discovered by genomic data
      mining. It could hydrolyze racemic o-chloromandelonitrile to (R)-o-chloromandelic
      acid with high enantioselectivity (ee 98.2 %). GPnor51 was overexpressed in
      Escherichia coli BL21 (DE3), purified, and its catalytic properties studied.
      GPnor51 had a broad substrate acceptance toward various nitriles with structure
      diversity. It was an arylacetonitrilase that uses arylacetonitriles as optimal
      substrates. The V max and K m of GPnor51 towards o-chloromandelonitrile were 1.9
      MUmol min(-1) mg(-1) protein and 0.38 mM, respectively. GPnor51 also demonstrated
      high enantioselectivity toward mandelonitrile and other substituted
      mandelonitrile. CONCLUSION: This enzyme has a great potential for commercial
      production of optically pure (R)-mandelic acid and its derivatives.

PMID- 25854993
TI  - Micro-scale procedure for enzyme immobilization screening and operational
      stability assays.
AB  - OBJECTIVE: A simple and inexpensive methodology, based on the use of micro
      centrifuge filter tubes, is proposed for establishing the best enzyme
      immobilization conditions. RESULTS: The immobilized biocatalyst is located inside
      the filter holder during the whole protocol, thus facilitating the incubations,
      filtrations and washings. This procedure minimizes the amount of enzyme and solid
      carrier needed, and allows exploring different immobilization parameters (pH,
      buffer concentration, enzyme/carrier ratio, incubation time, etc.) in a fast
      manner. The handling of immobilized enzymes using micro-centrifuge filter tubes
      can also be applied to assess the apparent activity of the biocatalysts, as well
      as their reuse in successive batch reaction cycles. The usefulness of the
      proposed methodology is shown by the determination of the optimum pH for the
      immobilization of an inulinase (Fructozyme L) on two anion-exchange
      polymethacrylate resins (Sepabeads EC-EA and Sepabeads EC-HA). CONCLUSION: The
      micro-scale procedure described here will help to overcome the lack of guidelines
      that usually govern the selection of an immobilization method, thus favouring the
      development of stable and robust immobilized enzymes that can withstand harsh
      operating conditions in industry.

PMID- 25854995
TI  - Simultaneous electricity generation and microbially-assisted electrosynthesis in
      ceramic MFCs.
AB  - To date, the development of microbially assisted synthesis in Bioelectrochemical
      Systems (BESs) has focused on mechanisms that consume energy in order to drive
      the electrosynthesis process. This work reports--for the first time--on novel
      ceramic MFC systems that generate electricity whilst simultaneously driving the
      electrosynthesis of useful chemical products. A novel, inexpensive and low
      maintenance MFC demonstrated electrical power production and implementation into
      a practical application. Terracotta based tubular MFCs were able to produce
      sufficient power to operate an LED continuously over a 7 day period with a
      concomitant 92% COD reduction. Whilst the MFCs were generating energy, an
      alkaline solution was produced on the cathode that was directly related to the
      amount of power generated. The alkaline catholyte was able to fix CO2 into
      carbonate/bicarbonate salts. This approach implies carbon capture and storage
      (CCS), effectively capturing CO2 through wet caustic 'scrubbing' on the cathode,
      which ultimately locks carbon dioxide.

PMID- 25854994
TI  - Assessment of different energy delivery settings in laser and LED phototherapies
      in the inflammatory process of rat's TMJ induced by carrageenan.
AB  - Temporomandibular disorders (TMDs) are mostly inflammatory conditions widespread
      in the population. Previous studies have shown positive effects of either laser
      or light-emitting diode (LED) phototherapies on treating TMDs, but their action
      and mechanism in the inflammatory infiltrate of the temporomandibular joint are
      still poorly understood. The aim of this study was to assess, through
      histological analysis, the effectiveness of using laser light (lambda 780 nm, 70
      mW, continous wave (CW), 10 J) and LED (lambda 850 +/- 10 nm, 100 mW, CW, 10 J)
      on the inflammation of the temporomandibular joint of rats induced by
      carrageenan. Forty-five animals were divided into three groups with five animals
      each according to the experimental times of 2, 3, and 7 days: inflammation,
      inflammation+laser phototherapy, and inflammation+LED phototherapy. The first
      irradiation was performed 24 h after induction with an interval of 48 h between
      sessions. After animal death, specimens were processed and stained with
      hematoxylin-eosin (HE) and picrosirius. Then, the samples were examined
      histologically. Data were statistically analyzed. The inflammation group showed
      mild to moderate chronic inflammatory infiltrate between bone trabecules of the
      condyle. Over the time course of the study in the laser group, the region of the
      condyle presented mild chronic inflammation and intense vascularization. In the
      LED group, the condyle showed aspects of normality and absence of inflammation in
      some specimens. In all the time points, the laser-irradiated groups showed
      greater amount of collagen deposition in the condyle (p = 0.04) and in the disc
      (p = 0.03) when compared to the inflammation and LED groups, respectively. Laser-
      and LED-treated groups demonstrate a smaller number of layers of the synovial
      membrane when compared to the non-irradiated groups. It was concluded that, in
      general, laser and LED phototherapies resulted in a reduction of inflammatory
      infiltrate in the temporomandibular joint of rat. 

PMID- 25854996
TI  - Immobilization of membrane-bounded (S)-mandelate dehydrogenase in sol-gel matrix
      for electroenzymatic synthesis.
AB  - Membrane-bounded (S)-mandelate dehydrogenase has been immobilized on the surface
      of glassy carbon and carbon felt electrodes by encapsulation in a silica film
      obtained by sol-gel chemistry. Such bioelectrochemical system has been used for
      the first time for electroenzymatic conversion of (S)-mandelic acid to
      phenylglyoxylic acid. Apparent Km in this sol-gel matrix was 0.7 mM in the
      presence of ferrocenedimethanol, a value in the same order of magnitude as
      reported previously for vesicles in solution with other electron acceptors, i.e.,
      Fe(CN)6(3-) or 2,6-dichloroindophenol. The bioelectrode shows very good
      operational stability for more than 6 days. This stability was definitively
      improved by comparison to a bioelectrode prepared by simple adsorption of the
      proteins on the electrode surface (fast activity decrease during the first 15 h
      of experiment). Optimal electroenzymatic reaction was achieved at pH9 and 40 
      degrees C. Apparent Km of the protein activity was 3 times higher in carbon felt
      electrode than on glassy carbon surface, possibly because of transport
      limitations in the porous architecture of the carbon felt. A good correlation was
      found between electrochemical data and chromatographic characterization of the
      reaction products in the bioelectrochemical reactor.

PMID- 25854997
TI  - Hyphenated low-field NMR techniques: combining NMR with NIR, GPC/SEC and
      rheometry.
AB  - Hyphenated low-field NMR techniques are promising characterization methods for
      online process analytics and comprehensive offline studies of soft materials. By
      combining different analytical methods with low-field NMR, information on
      chemical and physical properties can be correlated with molecular dynamics and
      complementary chemical information. In this review, we present three hyphenated
      low-field NMR techniques: a combination of near-infrared spectroscopy and time
      domain NMR (TD-NMR) relaxometry, online (1) H-NMR spectroscopy measured directly
      after size exclusion chromatographic (SEC, also known as GPC) separation and a
      combination of rheometry and TD-NMR relaxometry for highly viscous materials.
      Case studies are reviewed that underline the possibilities and challenges of the
      different hyphenated low-field NMR methods. Copyright (c) 2015 John Wiley & Sons,
      Ltd. 

PMID- 25854998
TI  - Association between parental depressive symptoms and impaired bonding with the
      infant.
AB  - Impaired bonding with the infant is associated with maternal postpartum
      depression but has not been investigated extensively in fathers. The primary
      study aim was to evaluate associations between maternal and paternal depressive
      symptoms and impaired bonding with their infant. A secondary aim was to determine
      the associations between parents' marital problems and impaired bonding with the
      infant. The study is part of a population-based cohort project (UPPSAT) in
      Uppsala, Sweden. The Edinburgh Postnatal Depression Scale (EPDS) at 6 weeks and 6
      months postpartum and the Postpartum Bonding Questionnaire at 6 months postpartum
      were completed by 727 couples. The prevalence of impaired bonding was highest
      among couples in which both spouses had depressive symptoms. Impaired bonding was
      associated with higher EPDS scores in both mothers and fathers, as well as with
      experiencing a deteriorated marital relationship. The association between
      maternal and paternal impaired bonding and the mothers' and fathers' EPDS scores
      remained significant even after adjustment for relevant confounding factors.
      Depressive symptoms at 6 weeks postpartum are associated with impaired bonding
      with the infant at 6 months postpartum for both mothers and fathers. It is
      critical to screen for and prevent depressive symptoms in both parents during
      early parenthood.

PMID- 25854999
TI  - Chemical proteomic analysis of the potential toxicological mechanisms of
      microcystin-RR in zebrafish (Danio rerio) liver.
AB  - Microcystins (MCs) are common toxins produced by freshwater cyanobacteria, and
      they represent a potential health risk to aquatic organisms and animals,
      including humans. Specific inhibition of protein phosphatases 1 and 2A is
      considered the typical mechanism of MCs toxicity, but the exact mechanism has not
      been fully elucidated. To further our understanding of the toxicological
      mechanisms induced by MCs, this study is the first to use a chemical proteomic
      approach to screen proteins that exhibit special interactions with MC-arginine
      arginine (MC-RR) from zebrafish (Danio rerio) liver. Seventeen proteins were
      identified via affinity blocking test. Integration of the results of previous
      studies and this study revealed that these proteins play a crucial role in
      various toxic phenomena of liver induced by MCs, such as the disruption of
      cytoskeleton assembly, oxidative stress, and metabolic disorder. Moreover, in
      addition to inhibition of protein phosphate activity, the overall toxicity of MCs
      was simultaneously modulated by the distribution of MCs in cells and their
      interactions with other target proteins. These results provide new insight into
      the mechanisms of hepatotoxicity induced by MCs. (c) 2015 Wiley Periodicals, Inc.
      Environ Toxicol 31: 1206-1216, 2016. 

PMID- 25855000
TI  - Calcium binding properties of calcium dependent protein kinase 1 (CaCDPK1) from
      Cicer arietinum.
AB  - Calcium plays a crucial role as a secondary messenger in all aspects of plant
      growth, development and survival. Calcium dependent protein kinases (CDPKs) are
      the major calcium decoders, which couple the changes in calcium level to an
      appropriate physiological response. The mechanism by which calcium regulates CDPK
      protein is not well understood. In this study, we investigated the interactions
      of Ca(2+) ions with the CDPK1 isoform of Cicer arietinum (CaCDPK1) using a
      combination of biophysical tools. CaCDPK1 has four different EF hands as
      predicted by protein sequence analysis. The fluorescence emission spectrum of
      CaCDPK1 showed quenching with a 5 nm red shift upon addition of calcium,
      indicating conformational changes in the tertiary structure. The plot of changes
      in intensity against calcium concentrations showed a biphasic curve with binding
      constants of 1.29 MUM and 120 MUM indicating two kinds of binding sites.
      Isothermal calorimetric (ITC) titration with CaCl2 also showed a biphasic curve
      with two binding constants of 0.027 MUM and 1.7 MUM. Circular dichroism (CD)
      spectra showed two prominent peaks at 208 and 222 nm indicating that CaCDPK1 is a
      alpha-helical rich protein. Calcium binding further increased the alpha-helical
      content of CaCDPK1 from 75 to 81%. Addition of calcium to CaCDPK1 also increased
      fluorescence of 8-anilinonaphthalene-1-sulfonic acid (ANS) indicating exposure of
      hydrophobic surfaces. Thus, on the whole this study provides evidence for calcium
      induced conformational changes, exposure of hydrophobic surfaces and
      heterogeneity of EF hands in CaCDPK1.

PMID- 25855001
TI  - Body mass index trajectories and functional decline in older adults: Three-City
      Dijon cohort study.
AB  - Obesity, whose prevalence is increasing, is associated with poor functional
      status at older ages. However, much of this evidence is cross-sectional with
      little known about longitudinal associations. We examined associations of body
      mass index (BMI), and change in BMI, with change in objective [walking speed
      (WS)] and self-reported (disability) measures of motor decline. Analyses included
      participants (65-85 years) from the Dijon center of the Three-City study (France)
      with up to five WS (N = 4007) and six disability assessments (N = 4478) over 11
      years. Data were analyzed using regression models for repeated measures. Mean
      baseline WS was 153 cm/s. Compared to normal weight persons, obese participants
      at baseline walked slower and reported more disability; they also experienced 45%
      faster WS decline (-18.63 vs. -12.85 cm/s/10 years, P = 0.002). Participants who
      lost or gained weight had 47% (-18.85 cm/s/10 years, P < 0.001) and 33% (-17.08
      cm/s/10 years, P = 0.002) respectively greater WS decline than participants in
      the normal BMI change category. 24% of participants reported disability at least
      once during the follow-up, those who lost or gained weight had a 1.63 and 1.34
      respectively higher odds of disability than participants in the normal BMI change
      category (P = 0.001). Associations remained after adjustment for covariates. In
      conclusion, obesity is associated with worse motor performances, a higher risk of
      disability, and faster motor decline. Our results underline the interest of
      repeated BMI and motor assessments to identify those at higher risk of
      disability.

PMID- 25855002
TI  - Combined effect of tobacco smoking and alcohol drinking in the risk of head and
      neck cancers: a re-analysis of case-control studies using bi-dimensional spline
      models.
AB  - The synergistic effect of tobacco smoking and alcohol consumption on the risk of
      head and neck cancers has been mainly investigated as a cross-product of
      categorical exposure, thus leading to loss of information. We propose a bi
      dimensional logistic spline model to investigate the interacting dose-response
      relationship of two continuous exposures (i.e., ethanol intake and tobacco
      smoking) on the risk of head and neck cancers, representing results through three
      dimensional graphs. This model was applied to a pool of hospital-based case
      control studies on head and neck cancers conducted in Italy and in the Vaud Swiss
      Canton between 1982 and 2000, including 1569 cases and 3147 controls. Among never
      drinkers and for all levels of ethanol intake, the risk of head and neck cancers
      steeply increased with increasing smoking intensity, starting from 1
      cigarette/day. The risk associated to ethanol intake increased with incrementing
      exposure among smokers, and a threshold effect at approximately 50 g/day emerged
      among never smokers. Compared to abstainers from both tobacco and alcohol
      consumption, the combined exposure to ethanol and/or cigarettes led to a steep
      increase of cancer risk up to a 35-fold higher risk (95 % confidence interval
      27.30-43.61) among people consuming 84 g/day of ethanol and 10 cigarettes/day.
      The highest risk was observed at the highest levels of alcohol and tobacco
      consumption. Our findings confirmed a combined effect of tobacco smoking and
      alcohol drinking on head and neck cancers risk, providing evidence that bi
      dimensional spline models could be a feasible and flexible method to explore the
      pattern of risks associated to two interacting continuous-exposure variables.

PMID- 25855003
TI  - Inflammatory bowel disease.
AB  - Scandinavian researchers have contributed to the present understanding of
      inflammatory bowel disease (IBD). Important epidemiological data and family risk
      factors have been reported from all the Nordic countries, original twin studies
      mainly from Denmark and Sweden, and relationships to cancer and surgery mostly
      from Sweden. In collaboration with the industry, development of medical compounds
      was for a long time in the front line of international research, and the
      Scandinavian countries participated in the clinical breakthrough of biologic
      treatment. At present, many Nordic centers are working in the forefront of IBD
      research. An increasing number of young investigators have entered the scene
      along with the extended distribution of University clinics and research
      laboratories in these countries. This presentation of IBD gives a brief overview
      in the fields of clinical epidemiology and molecular biology. Many areas are
      covered by International collaborations with partners from Nordic centers. IBD
      was a topic focused by the founders of Scandinavian Journal of Gastroenterology.
      After 50 years one may state that the journal's history reflects important pieces
      of scientific knowledge within these diseases. The early scope of Johannes Myren
      for IBD was shown through his work in the original World Association of
      Gastroenterology (OMG), and after 50 years we can clearly support the view that
      global perspectives in IBD are increasingly important. 

PMID- 25855005
TI  - Placebo effect in Parkinson's disease: Harnessing the mind in the treatment of
      PD.

PMID- 25855004
TI  - Age-related differences in the neural basis of the subjective vividness of
      memories: evidence from multivoxel pattern classification.
AB  - Although older adults often show reduced episodic memory accuracy, their ratings
      of the subjective vividness of their memories often equal or even exceed those of
      young adults. Such findings suggest that young and older adults may
      differentially access and/or weight different kinds of information in making
      vividness judgments. We examined this idea using multivoxel pattern
      classification of fMRI data to measure category representations while
      participants saw and remembered pictures of objects and scenes. Consistent with
      our hypothesis, there were age-related differences in how category
      representations related to the subjective sense of vividness. During remembering,
      older adults' vividness ratings were more related, relative to young adults', to
      category representations in prefrontal cortex. In contrast, young adults'
      vividness ratings were more related, relative to older adults, to category
      representations in parietal cortex. In addition, category representations were
      more correlated among posterior regions in young than in older adults, whereas
      correlations between PFC and posterior regions did not differ between the 2
      groups. Together, these results are consistent with the idea that young and older
      adults differentially weight different types of information in assessing
      subjective vividness of their memories. 

PMID- 25855006
TI  - The role of micronutrients and strategies for optimized continual glycerol
      production from carbon dioxide by Dunaliella tertiolecta.
AB  - The microalga Dunaliella tertiolecta synthesizes intracellular glycerol as an
      osmoticum to counteract external osmotic pressure in high saline environments.
      The species has recently been found to release and accumulate extracellular
      glycerol, making it a suitable candidate for sustainable industrial glycerol
      production if a sufficiently high product titre yield can be achieved. While
      macronutrients such as nitrogen and phosphorus are essential and well understood,
      this study seeks to understand the influence of the micronutrient profile on
      glycerol production. The effects of metallic elements calcium, magnesium,
      manganese, zinc, cobalt, copper, and iron, as well as boron, on glycerol
      production as well as cell growth were quantified. The relationship between cell
      density and glycerol productivity was also determined. Statistically, manganese
      recorded the highest improvement in glycerol production as well as cell growth.
      Further experiments showed that manganese availability was associated with higher
      superoxide dismutase formation, thus suggesting that glycerol production is
      negatively affected by oxidative stress and the manganese bound form of this
      enzyme is required in order to counteract reactive oxygen species in the cells. A
      minimum concentration of 8.25 * 10(-5)  g L(-1) manganese was sufficient to
      overcome this problem and achieve 10 g L(-1) extracellular glycerol, compared to
      4 g L(-1) without the addition of manganese. Unlike cell growth, extracellular
      glycerol production was found to be negatively affected by the amount of calcium
      present in the normal growth medium, most likely due to the lower cell
      permeability at high calcium concentrations. The inhibitory effects of iron also
      affected extracellular glycerol production more significantly than cell growth
      and several antagonistic interaction effects between various micronutrients were
      observed. This study indicates how the optimization of these small amounts of
      nutrients in a two-stage system can lead to a large enhancement in D. tertiolecta
      glycerol production and should be considered during the design of a large scale
      bioprocess for this alternative route to glycerol.

PMID- 25855007
TI  - Clinical features and prognosis of eyeball rupture: eye injury vitrectomy study.
AB  - BACKGROUND: The objective of the study was to delineate clinical characteristics,
      surgical interventions, anatomic and visual outcomes of ruptured eye balls after
      trauma, and establish the prognostic indicators, which can assist clinicians in
      making correct surgical decisions during globe exploration for ruptured eyes.
      DESIGN: The study design used was a multicentre prospective cohort study,
      including six university-affiliated tertiary hospitals. PARTICIPANTS: We selected
      242 cases of ruptured globe from the Eye Injury Vitrectomy Study database, until
      31 December 2012. METHODS: All selected cases underwent vitreoretinal surgery,
      enucleation or evisceration, and were followed up for at least 6 months. Age,
      visual acuity (VA) after injury, ocular trauma zone, time to surgery, corneal
      laceration, scleral wound, extrusion of iris or lens, ciliary body damage,
      intraocular haemorrhage, retinal detachment or defect, proliferative
      vitreoretinopathy (PVR) and choroidal damage were the predisposing factors
      evaluated by logistic regression models. MAIN OUTCOME MEASURES: We compared the
      pre-surgical indicators between cases of anatomically restored eyes with VA of
      4/200 or better, or eyes with initial no light perception restored light
      perception or better, and cases of VA worse than 4/200, silicone oil-sustained
      eyes, phthisis or enucleation. RESULTS: Nearly 40% of cases with ruptured globe
      were anatomically restored through vitreoretinal surgery. The closed-funnel
      retinal detachment or extensive retinal loss (odds ratio [OR] = 3.38, P = 0.026),
      PVR-C (OR = 3.45, P = 0.008), and choroidal damage (OR = 4.20, P = 0.004) were
      correlated with poor outcomes. CONCLUSION: The closed-funnel retinal detachment
      or extensive retinal loss, PVR-C, and choroidal damage are the risk factors for
      unfavourable outcomes in globe ruptures.

PMID- 25855008
TI  - Chronic toxicity evaluation of the flame retardant tris (2-butoxyethyl) phosphate
      (TBOEP) using Daphnia magna transcriptomic response.
AB  - Tris (2-butoxyethyl) phosphate (TBOEP) is an organophosphorous-containing flame
      retardant (OPFR) of high production volume used in a broad range of applications.
      The use of TBOEP containing products has resulted in its release and ubiquitous
      occurrence in the aquatic environment. In this study, Daphnia magna
      transcriptomic response was measured by microarray to evaluate sublethal effects
      of TBOEP as part of a multi-level biological approach including specific gene
      transcription measured by qRT-PCR, enzyme activity, and life-history endpoints
      (i.e., survival, growth and reproduction). Chronic exposure (21 d) to a range of
      sublethal concentrations of TBOEP (14.7-1470MUgL(-1)) did not impact growth,
      survival or reproduction, although the number of offspring decreased between the
      lowest and the highest dose. Gene transcription profiling by microarray analysis
      revealed that 101 genes were differentially transcribed in response to TBOEP
      (fold change treated/control +/-1, p<0.05). Most of the responding genes were
      involved in protein metabolism (9), biosynthesis (4) and energy metabolism (6)
      indicating that TBOEP could have chronic toxic effects on aquatic organisms at
      sublethal doses by disrupting essential biological pathways. Nine genes were
      found to be commonly affected by more than one dose, including a gene coding for
      cathepsin D and multiple isoforms of genes coding for hemoglobin, suggesting
      potential biomarkers of interest. Microarray results were confirmed by qRT-PCR
      and measurements at the protein level as cathepsin D enzymatic activity increased
      significantly in the highest dose treatment. Results highlight the relevance of
      using the transcriptomic response of D. magna as a first line of evidence to
      unravel the mode of action of chemicals. 

PMID- 25855010
TI  - The role of vitamin C as antioxidant in protection of biochemical and
      haematological stress induced by chlorpyrifos in freshwater fish Clarias
      batrachus.
AB  - The study was conducted to explore the modulatory effects of chlorpyrifos and
      protective role of vitamin C in tissues of Clarias batrachus. Treatments include
      E1 group (basal diet plus 1.65mgL(-1) CPF) and E2 group (basal diet+200mgkg body
      weight vitamin C and 1.65mgL(-1) CPF) along with a control group of fishes (fed
      on basal diet only). After 1, 7, 15, and 30d of treatment, fish tissues (brain,
      blood and liver) were used for the estimation of growth, biochemical and
      haematological parameters. The results of E1 group indicated significantly lower
      weight gain and survival rate. Brain AChE activity was inhibited. The RBC, Hb,
      respiratory burst activity, total protein and HSI were also reduced whereas WBC
      count, plasma glucose and haematocrit were elevated. In contrast, liver glycogen
      content, lactate dehydrogenase, alkaline and acid phosphatase activities were
      inhibited and malate dehydrogenase, aspartate, alanine amino transferase were
      enhanced. The E2 group of fish exhibited significant improvement in growth,
      survival, haematological indices, brain AChE, liver glycogen and oxidative enzyme
      activity. The findings support that dietary vitamin C supplementation might be
      helpful in abrogation of chlorpyrifos toxicity and improves growth, survival,
      biochemical and haematological conditions in fishes. 

PMID- 25855009
TI  - Development of a lipovitellin-based goldfish (Carassius auratus) vitellogenin
      ELISA for detection of environmental estrogens.
AB  - The susceptibility of vitellogenin (Vtg) to degradation is a major problem
      affecting the robustness of enzyme-linked immunosorbent assay (ELISA) for
      goldfish (Carassius auratus) Vtg. In this study, a phospholipoglycoprotein with
      molecular mass of ~420kDa was purified from goldfish egg extracts and it produced
      a single band corresponding to ~112kDa in SDS-polyacrylamide gel electrophoresis
      (SDS-PAGE). Additionally, the amino acid composition of the purified protein was
      comparable to that of lipovitellin (Lv) from other fish species. Thus, the
      purified protein was identified as goldfish Lv. Purified Lv and anti-Lv
      polyclonal antiserum were used to develop an ELISA with a detection range between
      31.25 and 1000ngmL(-)(1). The intra- and inter-assay coefficients of variation
      were 6.45% and 7.08%, respectively. The immunological similarity between goldfish
      Vtg and Lv was confirmed by immunoelectrophoresis and Western blot. Goldfish Lv
      showed higher stability than Vtg after -80 degrees C storage, multiple
      freeze/thaw cycles, and heat treatment. Moreover, the use of treated Lv in the
      ELISA did not change the slopes of standard curves. Parallelism between the Lv
      standard curve and plasma dilution curves of vitellogenic females confirmed the
      validity of the assay for quantifying plasma Vtg. The Lv-based Vtg ELISA was
      further applied to evaluate the estrogenic activity of monocrotophos pesticide. 

PMID- 25855011
TI  - Effects of chlorpyrifos on in vitro sex steroid production and thyroid follicular
      development in adult and larval Lake Sturgeon, Acipenser fulvescens.
AB  - Chlorpyrifos is a widely used organophosphate pesticide that has previously been
      shown to enter waterways in biologically relevant concentrations and has the
      potential to disrupt both thyroid hormone and sex steroid biosynthesis in
      vertebrates. Because gonadal maturation and larval development in Lake Sturgeon,
      Acipenser fulvescens, potentially coincide with the application of chlorpyrifos
      we examined the effects of chlorpyrifos on both thyroid follicular development in
      larval Lake Sturgeon, and sex hormone synthesis in adult Lake Sturgeon. For the
      first time, the present study reports steroidogenesis from testicular and ovarian
      tissue in Lake Sturgeon using an established in vitro bioassay. Furthermore,
      incubating gonad tissue with 5, 500 or 2000ngmL(-1) chlorpyrifos revealed an
      inhibitory effect on testosterone synthesis in both testicular (control,
      40.29pgmg(-1) tissue wet weight(-1)h(-1) compared to experimental, 21.84pgmg(-1)
      tissue wet weight(-1)h(-1)) and ovarian (control, 33.83pgmg(-1) tissue wet
      weight(-1)h(-1) compared to experimental, 15.19pgmg(-1) tissue wet weight(-1)h(
      1)) tissue. In a second series of experiments, larval Lake Sturgeon were exposed
      to equivalent concentrations of chlorpyrifos as above for 10days (d) between
      hatch and the onset of exogenous feeding. Larvae from each treatment group were
      raised until 67days post hatch (dph) and growth rates were compared alongside key
      indicators of thyroid follicle growth. Chlorpyrifos treatment had no effect on
      the measured indicators of thyroid follicular development. 

PMID- 25855012
TI  - Discovery of 2',4'-dimethoxychalcone as a Hsp90 inhibitor and its effect on
      iressa-resistant non-small cell lung cancer (NSCLC).
AB  - Heat shock protein 90 (Hsp90) is a ATP dependent molecular chaperone and has
      emerged as an attractive therapeutic target in the war on cancer due to its role
      in regulating maturation and stabilization of numerous oncogenic proteins. In
      this study, we discovered that 2',4'-dimethoxychalcone (1b) disrupted Hsp90
      chaperoning function and inhibited the growth of iressa-resistant non-small cell
      lung cancer (NSCLC, H1975). The result suggested that 2',4'-dimethoxychalcone
      (1b) could serve as a potential therapeutic lead to circumvent the drug
      resistance acquired by EGFR mutation and Met amplification. 

PMID- 25855013
TI  - Constituents of the aerial parts of Eclipta prostrata and their cytotoxicity on
      human ovarian cancer cells in vitro.
AB  - A new terthiophene, 3'-hydroxy-2,2':5',2"-terthiophene-3'-O-beta-D
      glucopyranoside (1) and a new oleanane-type saponin, echinocystic acid-3-O-(6-O
      acetyl)-beta-D-glucopyranoside (7) were isolated from the aerial parts of Eclipta
      prostrata L. Moreover, five thiophenes (2-6), seven triterpenoids (8-14), two
      coumestans (15 and 16), and four flavonoids (17-20) having previously known
      chemical structures were isolated during the same course of this study. All the
      isolates 1-20 were evaluated for their cytotoxicity against human ovarian cancer
      cells (SKOV3) using MTT assays. 

PMID- 25855015
TI  - Assessing options for treating haemophilia with inhibitors.

PMID- 25855016
TI  - Occupational hand eczema caused by nickel allergy and semi-quantified by
      dimethylglyoxime testing of the skin.

PMID- 25855017
TI  - Variants in MTHFR gene and neural tube defects susceptibility in China.
AB  - Neural tube defect (NTD) is a severe congenital birth abnormalities involving
      incomplete neural tube closure. 5, 10-methylenetetrahydrofolate reductase (MTHFR)
      gene plays key role in folate cycle and methylation cycle, which could affect the
      DNA synthesis, repair and methylation. In this study, we aim to investigate the
      correlation between MTHFR polymorphisms and NTD-affected pregnancy. There were
      444 participants involved in our study. Tag-SNPs were identified in HapMap
      Databases. Blood samples were collected from all subjects to further extract the
      genomic DNAs by TaqMan Blood DNA kits. We also carried out a meta-analysis based
      on previous published studies to further examine the association between MTHFR
      polymorphisms and NTD. In case-control study analysis, two SNPs were identified
      to be associated with NTD risk. The 677 C > T genetic variant was correlated with
      increased risk of NTD-affected pregnancy. However, the 1298 A > C polymorphism
      was shown to lower the risk of NTD-affected pregnancy. The protective role of
      1298 A > C polymorphisms was further supported by the result of meta-analysis.
      Our study revealed that the SNPs of 677C > T and 1298A > C in MTHFR were
      associated with NTD-affected pregnancy, in which 677C > T was a risk factor and
      in contrast 1298A > C was protective factor against NTD. Our results of meta
      analysis also revealed the 1298A > C MTHFR polymorphism play protective role in
      NTD. 

PMID- 25855018
TI  - Exploring the electronic properties and cation complexation of polyoxoaurates
      [Au(III)4X4Om](n-) (X = Si(IV), P(V), Ge(IV), As(V), and Se(IV)) using quantum
      chemical calculations.
AB  - Quantum chemical calculations were performed to explore the structural and
      electronic properties of the two polyoxoaurates, [Au(III)4As(V)4O20](8-) (Au4As4)
      and [Au(III)4Se(IV)4O16](4-) (Au4Se4), known to date, and a number of
      hypothetical polyoxoaurate derivatives comprising heteroatoms different from
      arsenic and selenium (namely, Si, Ge and P). In addition, the interactions of
      [Au(III)4X4Om](n-) (X = As, Se) with alkali-metal cations (Li(+), Na(+), K(+) and
      Rb(+)) are also analysed. The studies suggest that the geometry structure,
      electronic properties and nucleophilicity of oxygen atoms of these polyoxoaurates
      are tuned by the size or electronegativity of the heteroatoms (Si, Ge, P, As and
      Se). Then, the geometry of [Au(III)4X4Om](n-) (X = As and Se) coordinating with
      alkali cations from Li(+) to Rb(+) and the complexation energy between
      [Au(III)4X4Om](n-) and alkali cations were compared. The results show that the
      stability and electronic structure of heteropolyoxoaurates depend on the
      entrapped cations. On the basis of the complexation energy, it can be concluded
      that the ion-pairing effect in arsenate-capped oxoaurate is stronger than that in
      selenite-capped oxoaurate. These heteropolyoxoaurates are expected to play a role
      in aqueous behaviour, self-assembly characteristics of polyoxoaurates, ion
      recognition, selectivity studies and may exhibit potential guest-switchable redox
      properties. 

PMID- 25855019
TI  - Dietary intake of patients with moderate to severe COPD in relation to fat-free
      mass index: a cross-sectional study.
AB  - BACKGROUND: Fat-free mass (FFM) depletion has been shown to be a better predictor
      of mortality than BMI in chronic obstructive pulmonary disease (COPD) patients.
      The specific aim of the current study was to assess the nutritional status of
      stable COPD patients in relation to fat free mass index profiles. METHODS: We
      investigated 65 male moderate-to-severe stable COPD patients. A self-reported
      questionnaire was applied about general characteristics and smoking history.
      Nutritional intake was assessed by using a 54-item quantitative food frequency
      questionnaire. Weight, height, mid-upper arm circumference (MUAC), waist
      circumference (WC), handgrip strength and body composition measurements were
      taken by a trained dietitian. The data were analyzed with SPSS 15.0 software.
      RESULTS: The mean age of the patients was 62.1 +/- 8.9 years. Among all of the
      patients 13.8% was underweight (BMI < 21 kg/m(2)) and 18.5% had a low fat-free
      mass index (FFMI < 16 kg/m(2)). The percentages of the patients who did not meet
      the daily recommended intakes (RNI) were highest for magnesium (93.8%) and
      calcium (92.3%). Mean daily consumptions of milk-yogurt, red meat and fruits were
      significantly low in the low FFMI group compared to normal FFMI group (for all; p
      < 0.05). Patients with normal FFMI had significantly higher weight, height, WC,
      MUAC, handgrip strength, fat and fat-free mass than the patients with low FFMI
      (for all; p < 0.05). CONCLUSIONS: Dieticians should be aware of COPD patients
      with low FFMI in order to evaluate the nutritional intake and therefore plan
      nutritional strategies to improve prognosis of the disease.

PMID- 25855020
TI  - A high saturation factor in Overhauser DNP with nitroxide derivatives: the role
      of (14)N nuclear spin relaxation.
AB  - Overhauser DNP enhancements of toluene were measured at a magnetic field of 0.35
      Tesla in a series of chemically functionalized nitroxide radicals. We observe
      that the enhancements increase systematically with polarizer size and rotational
      correlation time. Examination of the saturation factor of (14)N nitroxides by
      pulsed ELDOR spectroscopy led to a quantitative interpretation of the
      enhancements, for which the saturation factor increases up to almost unity due to
      enhanced nuclear ((14)N) relaxation in the nitroxide radical. The observation has
      a direct impact on the choice of optimum DNP polarizers in liquids. 

PMID- 25855021
TI  - Tinea faciei caused by Trichophyton mentagrophytes (molecular type Arthroderma
      benhamiae ) mimics impetigo : a case report and literature review of cases in
      Japan.
AB  - A 36-year-old female elementary schoolteacher presented with aggregated serous
      papules surrounded by mild erythema, extending from both nasal wings/nostrils
      down to the upper lip. No improvement was seen following treatment of the lesions
      with topical antibiotics for impetigo. Potassium hydroxide (KOH) direct
      microscopy confirmed the presence of mycelia, and the infection was diagnosed as
      tinea faciei. The isolate was identified as Trichophyton mentagrophytes using
      morphological analysis and as Arthroderma benhamiae using genetic analysis. Here
      we describe that case and summarize the clinical features of other cases of A.
      benhamiae infection in Japan that have been reported in the literature. 

PMID- 25855022
TI  - [Deep-seated mycosis].

PMID- 25855023
TI  - [Dermatomycoses and medically important fungi that are necessary subjects of
      study for dermatology specialists -a personal experience].
AB  - Among the numerous skin diseases, dermatomycosis is the one caused by fungus
      (parasite) infecting the skin (host) . Once diagnosis is made, dermatomycosis can
      be cured with the use of appropriate anti-fungal drugs. Therefore, it is a much
      more easily treatable disease compareds with intractable skin diseases. From his
      own experience, the author shows that dermatomycoses are good subspecialties to
      deal with because many of them are controllable. At the same time, the author
      points out that basic research on medically important fungi needs to be done as
      collaborative studies with basic scientists and dermatology specialists. This
      brief review covers several topics including diagnostics of medical mycoses,
      imported medical mycoses, tinea, and cutaneous deep mycoses. 

PMID- 25855025
TI  - [Pathogenesis of chronic necrotizing pulmonary aspergillosis].
AB  - Chronic necrotizing pulmonary aspergillosis (CNPA) is a slowly progressive
      inflammatory destruction of lung tissue due to Aspergillus infection. The main
      radiographic features are chronic pulmonary infiltrates, progressive cavitation,
      and subsequent aspergilloma formation. Although pre-existing cavity is not seen,
      the presence of pre-existing airspaces such as emphysematous bullae, cannot be
      excluded. Chronic cavitary pulmonary aspergillosis (CCPA), which is synonymous
      with complex aspergilloma, shows one or more pre-existing and / or newly formed
      pulmonary cavities that may or may not contain an aspergilloma, and cavity
      expansion and / or increasing pericavitary infiltrates. CNPA can be distinguished
      from CCPA by careful observation of progression of the cavitary lesion if a
      series of adequate radiography films are available. In some cases, however, it is
      difficult to distinguish the two subtypes if prior radiographs are not available
      Aiso, intermediate or overlapping types may exist. We therefore clinically and
      therapeutically proposed the syndrome including both CNPA and CCPA as chronic
      progressive pulmonary aspergillosis (CPPA). 

PMID- 25855024
TI  - [Anti-Candida activity of aroma candy and its protective activity against murine
      oral candidiasis].
AB  - A daily eatable candy that has possible protective activity against oral
      candidiasis was experimentally produced. The candy was made from reduced-maltose
      as main constituent and from several natural products, such as oligonol
      (depolymerized polyphenols derived from lychee), cinnamon (cassia), citral, and
      capric acid, which are known to have anti-Candida activity in vitro and in vivo.
      The candy effectively inhibited the mycelial growth of C. albicans, even when it
      was diluted 1,000 times with culture media. We assessed the protective activity
      of the candy against murine candidiasis. When 50MUl of candy dissolved and
      diluted 4 times with water was administered 3 times into the oral cavity of
      Candida infected mice, the score of lesions on the Candida-infected tongues
      improved on day 2. These findings suggest that this candy has potential as food
      that provides protective activity against oral candidiasis. 

PMID- 25855026
TI  - [The effects of an aroma candy on oral Candida albicans colony-forming units
      (CFU) and oral hygiene states in healthy elderly carrying Candida albicans].
AB  - In a preceding paper, we showed that aroma candy containing oligonol, capric
      acid, and cinnamon (cassia) powder had potent inhibitory activity against
      mycelial growth of Candida albicans in vitro and protective activity against
      murine oral candidiasis. In order to assess the effects of this candy (the test
      candy) on oral C. albicans colony-forming units (CFU) and oral hygiene states, a
      placebo-controlled double-blind crossover comparative study was performed. Twenty
      subjects were divided into two groups. One group ingested the test candy in the
      first 7 days followed by 2 weeks washing-off period, then ingested the placebo
      candy (control candy) for 7 days. The other group was vice versa. C. albicans CFU
      in all oral rinse samples from the subjects before and after 7 days ingestion of
      candy was measured. The degree of oral malodor in all subjects was monitored
      using a portable measuring instrument. The results showed no statistically
      significant difference between test-candy group and placebo group for C. albicans
      CFU. However, C. albicans CFU in test-candy group with>4,000 CFUs was
      significantly decreased after 7 days ingestion of test-candy (p<0.05). Scores of
      oral malodor in the test-candy group was significantly decreased after 7 days
      ingestion of test-candy (p<0.05). A questionnaire survey of oral hygiene states
      indicated that in the test-candy group, oral malodor, glutinous feeling, and
      refreshing feeling significantly improved in comparison with control-candy group
      (p<0.05). Our study suggests that the aroma candy is effective in oral health
      care of elderly carrying C. albicans. 

PMID- 25855027
TI  - [Term 5: Neutrophil extracellular traps and inflammasomes].

PMID- 25855028
TI  - Lean adolescents achieve higher intensities but not higher energy expenditure
      while playing active video games compared with obese ones.
AB  - BACKGROUND: While decreased physical activity and increased sedentary behaviours
      are incriminated for their role in the progression of obesity, active video games
      (AVG) may offer a new alternative to increase energy expenditure in youth. This
      study is the first to examine the effect of a 1-h AVG play on lean and obese
      adolescents' energy expenditure. METHODS: Body composition and aerobic fitness
      were assessed in 19 obese and 12 lean adolescent boys (12-15 years old).
      Participants performed a 1-h AVG session (Kinect Sports technology) while wearing
      a portable indirect calorimeter (K4b2) to assess their energy expenditure and
      heart rate. RESULTS: Body weight (91.0 +/- 9.5 vs. 58.5 +/- 12.4 kg), body mass
      index (32.2 +/- 3.1 vs. 20.3 +/- 1.6 kg m(-2) ) and body fat (38.1 +/- 2.7 vs.
      13.4 +/- 3.9%) were significantly higher in obese adolescents (P < 0.001).
      Absolute energy expenditure was significantly higher in obese (P < 0.05) but not
      when corrected for body composition. Maximal heart rate reached during AVG was
      significantly higher in lean adolescents (190 +/- 25 vs. 183 +/- 28 bpm, P <
      0.05). Time spent between 3 and 6 METs (Metabolic Equivalent Task) was not
      different between groups but time spent above 6 METs was higher in lean
      adolescents (P < 0.05). CONCLUSION: Although lean and obese adolescent boys
      experienced similar energy expenditure relative to their body size during a 1-h
      Kinect AVG session, lean adolescents spent more time in moderate-to-vigorous
      physical activity.

PMID- 25855029
TI  - Clusterin glycopeptide variant characterization reveals significant site-specific
      glycan changes in the plasma of clear cell renal cell carcinoma.
AB  - Cancer-related alterations in protein glycosylation may serve as diagnostic or
      prognostic biomarkers or may be used for monitoring disease progression.
      Clusterin is a medium abundance, yet heavily glycosylated, glycoprotein that is
      upregulated in clear cell renal cell carcinoma (ccRCC) tumors. We recently
      reported that the N-glycan profile of clusterin is altered in the plasma of ccRCC
      patients. Here, we characterized the occupancy and the degree of heterogeneity of
      individual N-glycosylation sites of clusterin in the plasma of patients diagnosed
      with localized ccRCC, before and after curative nephrectomy (n = 40). To this
      end, we used tandem mass spectrometry of immunoaffinity-enriched plasma samples
      to analyze the individual glycosylation sites in clusterin. We determined the
      levels of targeted clusterin glycoforms containing either a biantennary
      digalactosylated disialylated (A2G2S2) glycan or a core fucosylated biantennary
      digalactosylated disialylated (FA2G2S2) glycan at N-glycosite N374. We showed
      that the presence of these two clusterin glycoforms differed significantly in the
      plasma of patients prior to and after curative nephrectomy for localized ccRCC.
      Removal of ccRCC led to a significant increase in the levels of both FA2G2S2 and
      A2G2S2 glycans in plasma clusterin. These changes were further confirmed by
      lectin blotting of plasma clusterin. It is envisioned that these identified
      glycan alterations may provide an additional level of therapeutic or biomarker
      sensitivity than levels currently achievable by monitoring expression differences
      alone. 

PMID- 25855030
TI  - Impact of bioenergy production on ecosystem dynamics and services-a case study on
      U.K. Heathlands.
AB  - For sustainability's sake, the establishment of bioenergy production can no
      longer overlook the interactions between ecosystem and technological processes,
      to ensure the preservation of ecosystem functions that provide energy and other
      goods and services to the human being. In this paper, a bioenergy production
      system based on heathland biomass is investigated with the aim to explore how a
      system dynamics approach can help to analyze the impact of bioenergy production
      on ecosystem dynamics and services and vice versa. The effect of biomass
      harvesting on the heathland dynamics, ecosystem services such as biomass
      production and carbon capture, and its capacity to balance nitrogen inputs from
      atmospheric deposition and nitrogen recycling were analyzed. Harvesting was found
      to be beneficial for the maintenance of the heathland ecosystem if the biomass
      cut fraction is higher than 0.2 but lower than 0.6, but this will depend on the
      specific conditions of nitrogen deposition and nitrogen recycling. With 95%
      recycling of nitrogen, biomass production was increased by up to 25% for a cut
      fraction of 0.4, but at the expense of higher nitrogen accumulation and the
      system being less capable to withstand high atmospheric nitrogen deposition. 

PMID- 25855032
TI  - Understanding the effects of establishing various cutoff criteria in the
      definition of men with premature ejaculation.
AB  - INTRODUCTION: Over the past decade, professional organizations and consensus
      groups have offered a variety of definitions for premature ejaculation (PE), all
      generally including a set of common concepts but all varying in specific language
      and operationalization. Clearly articulated definitions of such conditions are
      important because they not only affect prevalence rates but also diagnostic
      inclusion-who is deemed to have the condition and therefore who might be eligible
      for treatment. AIM: The current study had two goals: (i) to examine the effects
      on prevalence rates of moving the cutoff points from more stringent to less
      stringent for each of three PE criteria-ejaculatory latency, distress, and
      ejaculating before desired; and (ii) to explore in detail the relationships among
      the three criteria. METHODS: Using an Internet-based sample of 1,183 men, we
      examined the responses of 374 with PE-type symptoms based on consensus
      definitions, and determined the effect of decreasing restrictions on the cutoff
      criteria. In addition, we calculated both correlations and concordance rates
      among criteria. RESULTS: Numeric and graphic depiction of the effects of moving
      the cutoff point for each of the three criteria is provided in the URL "PE
      Prevalence," a dynamic tool developed specifically for this study
      (https://sites.google.com/a/valpo.edu/PEprevalence/). In addition, statistical
      relationships among the PE criteria suggest sufficient independence to warrant
      inclusion of all three in a diagnostic procedure as well as to consider a 2
      minute ejaculatory latency as the threshold for a PE diagnosis. CONCLUSIONS:
      Based on our data, clinicians should approach the 1-minute ejaculatory latency
      time (ELT) criterion with flexibility, considering ELTs up to 2 minutes for a PE
      diagnosis. At the same time, frequency of occurrence of either ejaculating before
      desired or of distress about the condition, as long as they reach at least 50% of
      the time, had only minor impact on PE diagnostic inclusion.

PMID- 25855031
TI  - The biliary epithelium presents antigens to and activates natural killer T cells.
AB  - Cholangiocytes express antigen-presenting molecules, but it has been unclear
      whether they can present antigens. Natural killer T (NKT) cells respond to lipid
      antigens presented by the major histocompatibility complex class I-like molecule
      CD1d and are abundant in the liver. We investigated whether cholangiocytes
      express CD1d and present lipid antigens to NKT cells and how CD1d expression
      varies in healthy and diseased bile ducts. Murine and human cholangiocyte cell
      lines as well as human primary cholangiocytes expressed CD1d as determined by
      flow cytometry and western blotting. Murine cholangiocyte cell lines were able to
      present both exogenous and endogenous lipid antigens to invariant and
      noninvariant NKT cell hybridomas and primary NKT cells in a CD1d-dependent
      manner. A human cholangiocyte cell line, cholangiocarcinoma cell lines, and human
      primary cholangiocytes also presented exogenous CD1d-restricted antigens to
      invariant NKT cell clones. CD1d expression was down-regulated in the biliary
      epithelium of patients with late primary sclerosing cholangitis, primary biliary
      cirrhosis, and alcoholic cirrhosis compared to healthy controls. CONCLUSIONS:
      Cholangiocytes express CD1d and present antigens to NKT cells and CD1d expression
      is down-regulated in diseased biliary epithelium, findings which show that the
      biliary epithelium can activate an important lymphocyte subset of the liver. This
      is a potentially important immune pathway in the biliary system, which may be
      capable of regulating inflammation in the context of biliary disease.

PMID- 25855034
TI  - Nanodrop on a smooth solid surface with hidden roughness. Density functional
      theory considerations.
AB  - A nanodrop of a test fluid placed on a smooth surface of a solid material of
      nonuniform density which covers a rough solid surface (hidden roughness) is
      examined, on the basis of the density functional theory (DFT), in the presence of
      an external perturbative force parallel to the surface. The contact angles which
      the drop profile makes with the surface at the leading edges of the drop are
      determined as functions of drop size and perturbative external force. A critical
      sticking force, defined as the largest value of the perturbative force for which
      the drop remains at equilibrium, is determined and its dependence on the size of
      the drop is explained on the basis of the shape of the interaction potential
      generated by the solid in vicinity of the leading edges of the drop. For even
      larger values of the perturbative force no drop-like solution of the Euler
      Lagrange equation of the DFT was found. The upper bound of the inclination angle
      of a surface containing a macroscopic drop is estimated on the basis of results
      obtained for nanodrops and some experimental results are interpreted. The main
      conclusion is that the hidden roughness has a similar effect on the drop features
      as the traditionally considered physical and chemical roughnesses. 

PMID- 25855033
TI  - Tor1, Sch9 and PKA downregulation in quiescence rely on Mtl1 to preserve
      mitochondrial integrity and cell survival.
AB  - Here we show that Mtl1, member of the cell wall integrity pathway of
      Saccharomyces cerevisiae, plays a positive role in chronological life span (CLS).
      The absence of Mtl1 shortens CLS and causes impairment in the mitochondrial
      function. This is reflected in a descent in oxygen consumption during the
      postdiauxic state, an increase in the uncoupled respiration and mitochondrial
      membrane potential and also a descent in aconitase activity. We demonstrate that
      all these effects are a consequence of signalling defects suppressed by TOR1
      (target of rapamycin) and SCH9 deletion and less efficiently by Protein kinase A
      (PKA) inactivation. Mtl1 also plays a role in the regulation of both Bcy1
      stability and phosphorylation, mainly in response to glucose depletion. In
      postdiauxic phase and in conditions of glucose depletion, Mtl1 negatively
      regulates TOR1 function leading to Sch9 inactivation and Bcy1 phosphorylation
      converging in PKA inhibition. Slt2/Mpk1 kinase partially contributes to Bcy1
      phosphorylation, although additional targets are not excluded. Mtl1 links
      mitochondrial dysfunction with TOR and PKA pathways in quiescence, glucose being
      the main signalling molecule. 

PMID- 25855035
TI  - A high performance sensor for triaxial cutting force measurement in turning.
AB  - This paper presents a high performance triaxial cutting force sensor with
      excellent accuracy, favorable natural frequency and acceptable cross-interference
      for high speed turning process. Octagonal ring is selected as sensitive element
      of the designed sensor, which is drawn inspiration from ring theory. A novel
      structure of two mutual-perpendicular octagonal rings is proposed and three
      Wheatstone full bridge circuits are specially organized in order to obtain
      triaxial cutting force components and restrain cross-interference. Firstly, the
      newly developed sensor is tested in static calibration; test results indicate
      that the sensor possesses outstanding accuracy in the range of 0.38%-0.83%.
      Secondly, impacting modal tests are conducted to identify the natural frequencies
      of the sensor in triaxial directions (i.e., 1147 Hz, 1122 Hz and 2035 Hz), which
      implies that the devised sensor can be used for cutting force measurement in a
      high speed lathe when the spindle speed does not exceed 17,205 rev/min in
      continuous cutting condition. Finally, an application of the sensor in turning
      process is operated to show its performance for real-time cutting force
      measurement; the measured cutting forces demonstrate a good accordance with the
      variation of cutting parameters. Thus, the developed sensor possesses perfect
      properties and it gains great potential for real-time cutting force measurement
      in turning. 

PMID- 25855036
TI  - Network design and quality checks in automatic orientation of close-range
      photogrammetric blocks.
AB  - Due to the recent improvements of automatic measurement procedures in
      photogrammetry, multi-view 3D reconstruction technologies are becoming a
      favourite survey tool. Rapidly widening structure-from-motion (SfM) software
      packages offer significantly easier image processing workflows than traditional
      photogrammetry packages. However, while most orientation and surface
      reconstruction strategies will almost always succeed in any given task,
      estimating the quality of the result is, to some extent, still an open issue. An
      assessment of the precision and reliability of block orientation is necessary and
      should be included in every processing pipeline. Such a need was clearly felt
      from the results of close-range photogrammetric surveys of in situ full-scale and
      laboratory-scale experiments. In order to study the impact of the block control
      and the camera network design on the block orientation accuracy, a series of
      Monte Carlo simulations was performed. Two image block configurations were
      investigated: a single pseudo-normal strip and a circular highly-convergent
      block. The influence of surveying and data processing choices, such as the number
      and accuracy of the ground control points, autofocus and camera calibration was
      investigated. The research highlights the most significant aspects and processes
      to be taken into account for adequate in situ and laboratory surveys, when modern
      SfM software packages are used, and evaluates their effect on the quality of the
      results of the surface reconstruction. 

PMID- 25855037
TI  - Sensing features of long period gratings in hollow core fibers.
AB  - We report on the investigation of the sensing features of the Long-Period fiber
      Gratings (LPGs) fabricated in hollow core photonic crystal fibers (HC-PCFs) by
      the pressure assisted Electric Arc Discharge (EAD) technique. In particular, the
      characterization of the LPG in terms of shift in resonant wavelengths and changes
      in attenuation band depth to the environmental parameters: strain, temperature,
      curvature, refractive index and pressure is presented. The achieved results show
      that LPGs in HC-PCFs represent a novel high performance sensing platform for
      measurements of different physical parameters including strain, temperature and,
      especially, for measurements of environmental pressure. The pressure sensitivity
      enhancement is about four times greater if we compare LPGs in HC and standard
      fibers. Moreover, differently from LPGs in standard fibers, these LPGs realized
      in innovative fibers, i.e., the HC-PCFs, are not sensitive to surrounding
      refractive index. 

PMID- 25855038
TI  - Piezoelectric micromachined ultrasound transducer (PMUT) arrays for integrated
      sensing, actuation and imaging.
AB  - Many applications of ultrasound for sensing, actuation and imaging require
      miniaturized and low power transducers and transducer arrays integrated with
      electronic systems. Piezoelectric micromachined ultrasound transducers (PMUTs),
      diaphragm-like thin film flexural transducers typically formed on silicon
      substrates, are a potential solution for integrated transducer arrays. This paper
      presents an overview of the current development status of PMUTs and a discussion
      of their suitability for miniaturized and integrated devices. The thin film
      piezoelectric materials required to functionalize these devices are discussed,
      followed by the microfabrication techniques used to create PMUT elements and the
      constraints the fabrication imposes on device design. Approaches for electrical
      interconnection and integration with on-chip electronics are discussed.
      Electrical and acoustic measurements from fabricated PMUT arrays with up to 320
      diaphragm elements are presented. The PMUTs are shown to be broadband devices
      with an operating frequency which is tunable by tailoring the lateral dimensions
      of the flexural membrane or the thicknesses of the constituent layers. Finally,
      the outlook for future development of PMUT technology and the potential
      applications made feasible by integrated PMUT devices are discussed. 

PMID- 25855039
TI  - Health information wanted and obtained from doctors/nurses: a comparison of
      Chinese cancer patients and family caregivers.
AB  - PURPOSE: To assess and compare health information wanted and obtained from
      doctors/nurses by Chinese cancer patients and family caregivers. RESEARCH
      QUESTIONS: (1) What are the instrument's psychometrics in Chinese cancer patients
      and family caregivers? (2) How might Chinese cancer patients and family
      caregivers differ in the amount of different types of health information they
      want to have? and (3) How might Chinese cancer patients and family caregivers
      differ in the amount of different types of information they were able to obtain
      from doctors/nurses? METHODS: This was a cross-sectional study using a paper-pen
      questionnaire. A total of 198 participants (79 cancer patients; 119 family
      caregivers) from a general hospital in Sichuan, China completed the instrument in
      March 2014. RESULTS: The instrument has excellent reliability and validity.
      Participants wanted to have a wide range of health information, including but not
      limited to information about diagnosis or treatment. Across all types of
      information, participants obtained from doctors/nurses significantly less than
      what they wanted. The discrepancy between information wanted and obtained varied
      across different types of information. The discrepancy was largest for
      information about complementary and alternative medicine (CAM) and psychosocial
      aspects and smallest for information about diagnosis and self-care. Patients and
      caregivers did not differ in the amount of different types of information they
      wanted or obtained from medical professionals. CONCLUSIONS: There is a great need
      for providing more information to both patients and their families, particularly
      information about CAM and psychosocial aspects.

PMID- 25855040
TI  - Longitudinal study on the impact of physical activity on the symptoms of lung
      cancer survivors.
AB  - PURPOSE: To examine the effect of physical activity on the physical and
      psychosocial symptoms of lung cancer survivors. METHODS: A longitudinal design
      was used in this study. Participants were recruited from the chest and surgical
      departments of medical centers in Taiwan. The instruments used were the Godin
      Leisure-Time Exercise Questionnaire and the Taiwanese version of the M.D.
      Anderson Symptom Inventory. RESULTS: In total, 185 survivors were followed up for
      6 months (response rate 66%). Disturbed sleep was the most prevalent symptom in
      the participants. A generalized estimating equation (GEE) method was employed to
      analyze the relationships among intensity of physical activity, symptom severity,
      and symptom interference in the daily life of the participants. Regarding symptom
      severity, significant differences were observed in fatigue, drowsiness, and
      disturbed sleep between the participants who engaged in moderate physical
      activity and those who did not engage in any physical activity. Regarding symptom
      interference, the participants who engaged in light physical activity experienced
      a significantly lower level of symptom interference than did those with a
      sedentary lifestyle. CONCLUSION: This is the first study to explore the role of
      physical activity in alleviating symptoms in lung cancer survivors by using the
      GEE method. The results suggest that physical activity plays an essential role in
      alleviating the physical and psychological symptoms of lung cancer survivors.

PMID- 25855041
TI  - Early percutaneous endoscopic gastrostomy and nutritional supplementation for
      patients with head and neck cancer: an Italian survey of head and neck radiation
      oncologists.
AB  - PURPOSE: The aim of this paper is to survey among Italian radiation oncologists
      about the role of nutritional supplementation and an early placement of
      endoscopic percutaneous gastrostomy in head and neck cancer patients treated with
      radiotherapy or chemo-radiotherapy. METHODS: The survey was carried out in 106
      Italian centers of radiation oncology through a SurveyMonkey online interface
      questionnaire. RESULTS: The response rate to the survey was of 63%, with 67
      analyzable questionnaires. The majority of the respondents do not use preventive
      nutritional supplement. In 73.1% of the cases, percutaneous endoscopic
      gastrostomy (PEG) is positioned only in case of necessity. The 82.1% of the
      interviewed physicians, indeed, argued that the preventive placement of the
      endoscopic percutaneous gastrostomy should not be a standard procedure.
      Nutritional counseling before starting a treatment is not a routine, but 88.1% of
      the respondents stated that this should represent a standard procedure.
      CONCLUSIONS: Although some studies agree that a reactive approach should be
      preferred to an early endoscopic percutaneous gastrostomy placement, firm
      evidences and a clear consensus are still lacking. This survey shows a wide
      agreement about both timing and criteria for endoscopic percutaneous gastrostomy
      placement; however, the management of nutritional supplementation in head and
      neck cancer patients appears to be still widely variable and to deserve more
      focused studies.

PMID- 25855042
TI  - Identification of a quorum sensing pheromone posttranslationally farnesylated at
      the internal tryptophan residue from Bacillus subtilis subsp. natto.
AB  - Bacillus subtilis subsp. natto produces poly-gamma-glutamic acid under the
      control of quorum sensing. We identified ComXnatto pheromone as the quorum
      sensing pheromone with an amino acid sequence of Lys-Trp-Pro-Pro-Ile-Glu and the
      tryptophan residue posttranslationally modified by a farnesyl group. ComXnatto
      pheromone is unique in the sense that the 5th tryptophan residue from the C
      terminal is farnesylated. 

PMID- 25855043
TI  - Examining the uncertain origin and management role of martens on Prince of Wales
      Island, Alaska.
AB  - Conservation biologists are generally united in efforts to curtail the spread of
      non-native species globally. However, the colonization history of a species is
      not always certain, and whether a species is considered non-native or native
      depends on the conservation benchmark. Such ambiguities have led to inconsistent
      management. Within the Tongass National Forest of Alaska, the status of American
      marten (Martes americana) on the largest, most biologically diverse and
      deforested island, Prince of Wales (POW), is unclear. Ten martens were released
      to POW in the early 1930s, and it was generally believed to be the founding
      event, although this has been questioned. The uncertainty surrounding when and
      how martens colonized POW complicates management, especially because martens were
      selected as a design species for the Tongass. To explore the history of martens
      of POW we reviewed other plausible routes of colonization; genetically and
      isotopically analyzed putative marten fossils deposited in the late Pleistocene
      and early Holocene to verify marten occupancy of POW; and used contemporary
      genetic data from martens on POW and the mainland in coalescent simulations to
      identify the probable source of the present-day marten population on POW. We
      found evidence for multiple routes of colonization by forest-associated mammals
      beginning in the Holocene, which were likely used by American martens to
      naturally colonize POW. Although we cannot rule out human-assisted movement of
      martens by Alaskan Natives or fur trappers, we suggest that martens be managed
      for persistence on POW. More generally, our findings illustrate the difficulty of
      labeling species as non-native or native, even when genetic and paleo-ecological
      data are available, and support the notion that community resilience or species
      invasiveness should be prioritized when making management decisions rather than
      more subjective and less certain conservation benchmarks. 

PMID- 25855044
TI  - E-health Support in People with Parkinson's Disease with Smart Glasses: A Survey
      of User Requirements and Expectations in the Netherlands.
AB  - Recent advances in smart glasses, wearable computers in the form of glasses,
      bring new therapeutic and monitoring possibilities for people with Parkinson's
      disease (PD). For example, it can provide visual and auditory cues during
      activities of daily living that have long been used to improve gait disturbances.
      Furthermore, smart glasses can personalize therapies based on the state of the
      user and/or the user environment in real-time using object recognition and motion
      tracking. To provide guidelines for developers in creating new PD applications
      for smart glasses, a self-reported questionnaire was designed to survey the
      requirements, constraints, and attitudes of people with PD with respect to this
      new technology. The survey was advertised online over an 11 month period on the
      website of the Parkinson Vereninging. The results were derived from 62
      participants (54.8% men and 45.2% women, average age of 65.7 +/- 9.1),
      representing a response rate of 79.5% . The participants were overall very
      enthusiastic about smart glasses as an assistive technology to facilitate daily
      living activities, especially its potential to self-manage motor problems and
      provide navigational guidance, thereby restoring their confidence and
      independence. The reported level of usage of mobile technologies like tablets and
      smartphones suggests that smart glasses could be adopted relatively easily,
      especially by younger people with PD. However, the respondents were concerned
      about the cost, appearance, efficacy, and potential side effects of smart
      glasses. To accommodate a wide range of symptoms, personal preferences, and
      comfort level with technology, smart glasses should be designed to allow simple
      operation and personalization. 

PMID- 25855045
TI  - Adherence to Tobacco Dependence Treatment Among HIV-Infected Smokers.
AB  - High prevalence of tobacco use and low success in quitting remain significant
      problems for reducing disease burden among HIV-infected persons. This study's
      purpose was to examine participant responsiveness and tobacco dependence
      treatment adherence and their influences on tobacco abstinence among HIV-infected
      patients. This non-randomized study included HIV-infected smokers 18 years of age
      or older, who smoked at least 5 cigarettes per day, and had an interest in
      quitting smoking in the next 30 days. HIV-infected smokers (n = 247) received a
      12-week tobacco dependence treatment intervention that included pharmacotherapy
      and telephone counseling. Younger age and non-White race were associated with
      lower adherence to pharmacotherapy. Younger age, non-White race, and increased
      monthly binge drinking were associated with lower adherence to telephone
      counseling. High participant responsiveness was associated with adherence to
      pharmacotherapy, counseling, and abstinence. Development and testing of
      interventions to improve adherence to evidence-based tobacco dependence treatment
      is warranted.

PMID- 25855046
TI  - Predictors of HIV Disclosure in Infected Persons Presenting to Establish Care.
AB  - Persons receiving effective HIV treatment experience longevity and improvement in
      quality of life. For those infected, social support is associated with improved
      medication adherence. Disclosure of infection status is likely a prerequisite for
      social support. However, little research describes patterns of HIV disclosure by
      infected persons. We retrospectively evaluated factors associated with disclosure
      among patients initiating HIV care at a university-based clinic from 2007 to
      2012. Of 490 persons initiating care, 13 % had not disclosed their HIV infection
      to anyone. Black race significantly predicted non-disclosure and persons living
      with a significant other or friends were more likely to have disclosed their HIV
      infection versus those living alone. CD4 + T lymphocyte count <200 was associated
      with nondisclosure and disclosure only to family members. Future research is
      needed to better understand factors associated with disclosure of HIV infection
      status, because this could enhance receipt of social support and contribute to
      improved HIV health outcomes.

PMID- 25855047
TI  - Prediction of HIV Virologic Failure Among Adolescents Using the Pediatric Symptom
      Checklist.
AB  - Psychosocial dysfunction is a risk factor for treatment non-adherence among
      children and adolescents. A previous study showed that high scores on the
      Pediatric Symptom Checklist (PSC) were associated with a history of HIV virologic
      failure. We assessed whether high scores on the PSC could predict virologic
      failure in HIV-infected youth. Caregivers of 234 adolescents between the ages of
      10 and 16 years were asked to complete a PSC at baseline. Elevated PSC scores
      were associated with virologic failure in the subsequent 6 months. PSC scores may
      help guide resource utilization when viral load monitoring is limited. 

PMID- 25855049
TI  - Corrigendum: Long non-coding RNAs and enhancer RNAs regulate the
      lipopolysaccharide-induced inflammatory response in human monocytes.

PMID- 25855048
TI  - MED12 somatic mutations in fibroadenomas and phyllodes tumours of the breast.
AB  - AIMS: Somatic mutations in exon 2 of the mediator complex subunit 12 (MED12) gene
      have been identified in 60% of breast fibroadenomas (FAs). The aim of this study
      was to define whether phyllodes tumours (PTs) would harbour MED12 somatic
      mutations in a way akin to FAs. METHODS AND RESULTS: A collection of 73
      fibroepithelial tumours (including 26 FAs, 25 benign PTs, nine borderline PTs and
      13 malignant PTs) from 64 patients was retrieved from the authors' institution.
      Sections from formalin-fixed paraffin-embedded (FFPE) blocks were microdissected
      to ensure an enrichment in neoplastic stromal elements of >70%. DNA samples
      extracted from tumour and matched normal tissues were subjected to Sanger
      sequencing of exon 2 of the MED12 gene. MED12 exon 2 somatic mutations, including
      28 somatic single nucleotide variants and 19 insertions and deletions, were found
      in 65%, 88%, 78% and 8% of FAs, benign PTs, borderline PTs and malignant PTs,
      respectively. Malignant PTs harboured MED12 exon 2 somatic mutations
      significantly less frequently than FAs, benign and borderline PTs. CONCLUSIONS:
      Although MED12 exon 2 somatic mutations probably constitute the driver genetic
      event of most FAs, benign and borderline PTs, our results suggest that the
      majority of malignant PTs may be driven by other genetic/epigenetic alterations.

PMID- 25855051
TI  - Combination-therapy with concurrent deferoxamine and deferiprone is effective in
      treating resistant cardiac iron-loading in aceruloplasminaemia.

PMID- 25855052
TI  - Safety of insulin analogs during pregnancy: a meta-analysis.
AB  - OBJECTIVE: The objective of this study was to assess the safety of four insulin
      analogs (aspart, lispro, glargine, and detemir) for the treatment of diabetes in
      pregnancy. METHODS: We searched Embase, Pubmed, and the Cochrane Central Register
      for Controlled Trials database through May 31, 2014. All articles were reviewed
      by two independent researchers, and if a discrepancy was noted, a third
      researcher was consulted. Results data were summarized by RevMan 5.2 software.
      RESULTS: Our search resulted in the retrieval and screening of 3519 studies. Of
      those, 24 studies met the eligibility criteria; the studies reported on a total
      of 3734 women with pre-gestational or gestational diabetes during pregnancy. The
      use of lispro was associated with lower rates of neonatal jaundice (RR = 0.63)
      and severe maternal hypoglycemia (RR = 0.33) than regular insulin. Lispro use was
      also associated with higher birth weight (WMD = 116.44) and an increased
      incidence of large for gestational age (LGA) births (RR = 1.42) compared with
      regular insulin. Rates of cesarean section and macrosomia were similar in
      pregnant women treated with aspart and regular insulin. Birth weights and rates
      of severe maternal hypoglycemia, respiratory dysfunction syndrome, and neonatal
      intensive care unit admission were similar after pregnant women were treated with
      glargine and NPH insulin. Rates of LGA, macrosomia, and neonatal hypoglycemia
      were similar after pregnant women were treated with detemir and NPH insulin.
      CONCLUSIONS: Aspart, glargine, and detemir are safe treatment options for
      diabetes during pregnancy; these insulin analogs did not increase complications
      for the mothers or fetuses in our study. However, lispro was related to higher
      birth weight and increased rate of LGA in neonates. More high-quality randomized
      controlled trials are needed to clarify the best treatment options for diabetes
      during pregnancy.

PMID- 25855050
TI  - Diverse involvement of isoforms and gene aberrations of Akt in human lung
      carcinomas.
AB  - Emerging evidence confirms a central role of Akt in cancer. To evaluate the
      relative contribution of deregulated Akt and their clinicopathological
      significance in lung carcinomas, overexpression, activation of Akt and AKT gene
      increases were investigated. Immunohistochemical staining for 108 cases revealed
      overexpression of total Akt, Akt1, Akt2 and Akt3 in 61.1, 47.2, 40.7 and 23.1%,
      respectively, and phosphorylated Akt in 42.6% of cases. Expression of total Akt,
      Akt2 and Akt3 were frequently observed in small cell carcinoma, but
      phosphorylated Akt and Akt1 were more frequently observed in squamous cell
      carcinoma. FISH analysis to evaluate gene increases of AKT1-3 revealed
      amplification of AKT1 in 4.2% and AKT1 increase by polysomy of chromosome 14 in
      27.3% of cases. For AKT2, amplification was observed in 3.2% and polysomy of
      chromosome 19 in 26.3% of cases. AKT3 increase was observed in 40.0% of cases
      only by polysomy of chromosome 1. Although "FISH-positive" AKT1 and AKT2 gene
      increases (amplification/high-level polysomy) were found exclusively in the cases
      overexpressing total Akt, Akt1 or Akt2, respectively, AKT3 increase was
      irrelevant of Akt3 expression. Statistically, expressions of Akt2, p-Akt and
      cytoplasmic-p-Akt were correlated with lymph node metastasis (P = 0.0479, P =
      0.0371 and P = 0.0310, respectively). Although AKT1 and AKT2 gene increase showed
      positive correlation with, or trend towards a positive correlation with tumor
      size (P = 0.0430, P = 0.0590, respectively), AKT3 did not. In conclusion, Akt
      isoforms are differentially involved in the pathological phenotype of lung
      carcinoma in a diverse manner. Because abnormality of Akt1/AKT1 and Akt2/AKT2
      correlated with clinicopathological profiles, Akt1/2-specific targeting may open
      a novel therapeutic window for the group showing Akt deregulation.

PMID- 25855053
TI  - The clinical characteristics and outcomes of cases with pure ovarian clear cell,
      mixed type and high-grade serous adenocarcinoma.
AB  - PURPOSE: This study aimed to compare the clinical characteristics and outcomes of
      the cases with pure ovarian clear cell adenocarcinoma (OCCC), mixed type (clear
      plus serous or clear plus endometrioid or serous plus clear plus endometrioid)
      ovarian adenocarcinoma (MOC) and high-grade serous ovarian adenocarcinoma
      (HGSOC). METHODS: A retrospective comparison was conducted in 32 cases with pure
      OCCC, 23 cases with MOC and 28 cases with HGSOC followed between January 1999 and
      October 2011. Clinico-pathologic characteristics including histopathologic
      subtypes, age, stage, presence of ascites and/or peritoneal carcinomatosis,
      endometriosis and optimal cytoreduction, and also survival rates were compared in
      these three groups. RESULTS: The cases with pure OCCC were younger than the cases
      with MOC and HGSOC (p = 0.004). The median pre-operative CA-125 level was lower
      in the pure OCCC than in MOC and HGSOC (p = 0.006) (p = 0.001, p = <0.001,
      respectively). Bilaterality and peritoneal carcinomatosis were more frequently
      seen in the HGSOC group (p = 0.001, p < 0.001, respectively). The majority of the
      cases (65 %) had stage I or II disease in the pure OCCC group, but most of the
      cases in the HGSOC group had advanced stage disease (p < 0.001). Endometriosis
      was found in 16 cases (16/55, 29 %) in the OCCC group. No significant difference
      was detected with regard to the median survival rate among three groups (p =
      0.517), while the stage of disease was found to be the only important factor for
      survival (p = 0.002). CONCLUSION: Pure OCCC, MOC and HGSOC represent distinct
      clinical characteristics. Clinical characteristics of MOC are more similar to
      those of HGSOC.

PMID- 25855054
TI  - Association of early maternal hypertriglyceridemia with pregnancy-induced
      hypertension.
AB  - BACKGROUND: Hypertensive diseases are directly responsible for 24 % of maternal
      deaths in India. A screening method is yet to be discovered to reduce the
      morbidity and mortality related to it. Serum triglyceride (TG) levels are
      reported to increase in hypertensive pregnant women. AIM: To predict pregnancy
      induced hypertension (PIH) by serum triglyceride values. METHOD: This study is a
      prospective cohort study that was conducted over three hundred normotensive,
      primigravida women with singleton pregnancy at 14-20 weeks of gestation. These
      were divided into two groups on the basis of their TG concentration estimated at
      14-20 weeks of gestation. The pregnancy was then followed till delivery and,
      signs and symptoms of PIH were noted in both the groups. RESULTS: Out of 300
      women, 210 women completed the study. Fifty-nine women developed PIH and 151
      women remained normotensive. Among 59 women, 45 women had raised TG values i.e.,
      >=160 mg/dL and 14 women were with normal TG levels i.e., <160 mg/dL. A
      significant positive correlation was found between serum TG concentration and
      systolic and diastolic blood pressure. It was observed that a cutoff of 162.50
      mg/dL for TG could reliably predict PIH with sensitivity of 76 % and specificity
      of 85 %. Also, the mothers with hypertriglyceridemia were found to be at higher
      risk of developing early-onset PIH. CONCLUSION: Our study supports the evidence
      that early pregnancy hypertriglyceridemia is associated with an increased risk of
      PIH.

PMID- 25855055
TI  - Lactobacilli vaginal colonisation after oral consumption of Respecta((r))
      complex: a randomised controlled pilot study.
AB  - PURPOSE: The aim of the current pilot study was to determine if oral consumption
      of a combination of two probiotics; L. acidophilus La-14, L. rhamnosus HN001, and
      bovine lactoferrin (Respecta((r)) complex), would lead to the detection with
      molecular techniques of the consumed probiotic strains in the vagina. METHODS:
      Healthy volunteers (40) consumed the study product twice daily for 2 weeks.
      Vaginal swabs were collected at 0, 1, 2 and 3 weeks and analysed for the consumed
      organisms by qPCR. RESULTS: Vaginal L. rhamnosus and L. acidophilus levels were
      significantly increased on days 14 and 21. On days 14 and 21 a significant number
      of women had increased levels of vaginal L. acidophilus and on days 7 and 21 a
      significant number of women had increased levels of vaginal L. rhamnosus.
      CONCLUSIONS: Consumption of L. acidophilus La-14, L. rhamnosus HN001 in
      combination with bovine lactoferrin leads to vaginal detection; even 1 week after
      consumption was stopped. This provides a basis for future studies on urogenital
      tract health.

PMID- 25855057
TI  - The Social Interaction Phobia Scale: Continued support for the psychometric
      validity of the SIPS using clinical and non-clinical samples.
AB  - The present study sought to extend findings supporting the psychometric validity
      of a promising measure of social anxiety (SA) symptoms, the Social Interaction
      Phobia Scale (SIPS; Carleton et al., 2009). Analyses were conducted using three
      samples: social anxiety disorder (SAD) patients, generalized anxiety disorder
      (GAD) patients, and healthy controls. SIPS scores of SAD patients demonstrated
      internal consistency and construct validity, and the previously demonstrated
      three-factor structure of the SIPS was replicated. Further, the SIPS total score
      uniquely predicted SA symptoms, and SIPS scores were significantly higher for SAD
      patients than GAD patients or controls. Two cut-off scores that discriminated SAD
      patients from GAD patients and from healthy controls were identified. The current
      study is the first to replicate the SIPS three-factor model in a large, treatment
      seeking sample of SAD patients and establish a cut-off score discriminating SAD
      from GAD patients. Findings support the SIPS as a valid, SAD-specific assessment
      instrument. 

PMID- 25855058
TI  - Nickel cobalt oxide hollow nanosponges as advanced electrocatalysts for the
      oxygen evolution reaction.
AB  - A class of novel nickel cobalt oxide hollow nanosponges were synthesized through
      a sodium borohydride reduction strategy. Due to their porous and hollow
      nanostructures, and synergetic effects between their components, the optimized
      nickel cobalt oxide nanosponges exhibited excellent catalytic activity towards
      oxygen evolution reaction. 

PMID- 25855056
TI  - Serum from calorie-restricted animals delays senescence and extends the lifespan
      of normal human fibroblasts in vitro.
AB  - The cumulative effects of cellular senescence and cell loss over time in various
      tissues and organs are considered major contributing factors to the ageing
      process. In various organisms, caloric restriction (CR) slows ageing and
      increases lifespan, at least in part, by activating nicotinamide adenine
      dinucleotide (NAD+)-dependent protein deacetylases of the sirtuin family. Here,
      we use an in vitro model of CR to study the effects of this dietary regime on
      replicative senescence, cellular lifespan and modulation of the SIRT1 signaling
      pathway in normal human diploid fibroblasts. We found that serum from calorie
      restricted animals was able to delay senescence and significantly increase
      replicative lifespan in these cells, when compared to serum from ad libitum fed
      animals. These effects correlated with CR-mediated increases in SIRT1 and
      decreases in p53 expression levels. In addition, we show that manipulation of
      SIRT1 levels by either over-expression or siRNA-mediated knockdown resulted in
      delayed and accelerated cellular senescence, respectively. Our results
      demonstrate that CR can delay senescence and increase replicative lifespan of
      normal human diploid fibroblasts in vitro and suggest that SIRT1 plays an
      important role in these processes. 

PMID- 25855059
TI  - Zinc Is Involved in Depression by Modulating G Protein-Coupled Receptor
      Heterodimerization.
AB  - 5-Hydroxytryptamine 1A receptor and galanin receptor 1 belong to the G protein
      coupled receptors superfamily, and they have been described to heterodimerize
      triggering an anomalous physiological state that would underlie depression. Zinc
      supplementation has been widely reported to improve treatment against major
      depressive disorder. Our work has focused on the study and characterization of
      these receptors and its relationships with zinc both under purified conditions
      and in cell culture. To this aim, we have designed a strategy to purify the
      receptors in a conformationally active state. We have used receptors tagged with
      the monoclonal Rho-1D4 antibody and employed ligand-assisted purification in
      order to successfully purify both receptors in a properly folded and active
      state. The interaction between both purified receptors has been analyzed by
      surface plasmon resonance in order to determine the kinetics of dimerization.
      Zinc effect on heteromer has also been tested using the same methodology but
      exposing the 5-hydroxytryptamine 1A receptor to zinc before the binding
      experiment. These results, combined with Forster resonance energy transfer (FRET)
      measurements, in the absence and presence of zinc, suggest that this ion is
      capable of disrupting this interaction. Moreover, molecular modeling suggests
      that there is a coincidence between zinc-binding sites and heterodimerization
      interfaces for the serotonin receptor. Our results establish a rational
      explanation for the role of zinc in the molecular processes associated with
      receptor-receptor interactions and its relationship with depression, in agreement
      with previously reported evidence for the positive effects of zinc in depression
      treatment, and the involvement of our target dimer in the same disease. 

PMID- 25855061
TI  - Upconversion luminescence mechanisms of Er(3+) ions under excitation of an 800 nm
      laser.
AB  - The fundamental processes of upconversion (UC) emissions from trivalent
      lanthanide ions are essential for designing and improving the performance of UC
      materials. However, UC mechanisms involve multiple processes in one system
      because of the abundant energy states, which make it a challenge to exclusively
      verify and quantitatively evaluate the dominant process. In this paper, the
      mechanisms of green and red emissions in Er(3+) doped NaYF4-glass ceramics under
      800 nm continuous wave laser excitation are studied via excitation power
      dependence, polarization-dependence, and the transient evolution. These UC
      emission properties are compared with those under single-/two-wavelength
      excitation in a pump-probe system of 800 nm and 1500 nm femtosecond lasers. These
      results indicate that the excited state absorption pathway of (4)I15/2 -> (4)I9/2
      -> (4)I13/2 -> (2)H11/2/(4)S3/2 plays the dominant role in the emission of the
      green band, and the cross relaxation pathway of (4)I11/2 + (4)I13/2 -> (4)F9/2 +
      (4)I15/2 plays the main role in the emission of the red band. 

PMID- 25855060
TI  - Nintedanib in non-small cell lung cancer: from preclinical to approval.
AB  - Angiogenesis is a driving force of a tumor's development. Targeting this process
      is an attractive option, as this is a feature shared by most of the solid tumors.
      A lot of antiangiogenic drugs have been developed following this path, including
      bevacizumab, sorafenib, sunitinib, vandetanib, ramucirumab, motesanib and many
      others. The latest drug of this class to be approved for patients with non-small
      cell lung cancer (NSCLC) was nintedanib, a triple angiokinase inhibitor. This
      molecule targets vascular endothelial growth factor (VEGF), platelet derived
      growth factor (PDGF) and fibroblast growth factor (FGF) pathways, avoiding the
      tumor's switch to normal escape mechanisms. The pharmacokinetic, pharmacodynamic
      and toxicity profiles of nintedanib have been tested in several studies. These
      trials revealed it to be very interesting, as this agent did not lead to the
      classical adverse events of other tyrosine kinase inhibitors. A phase III
      clinical trial that recently concluded provided us with relevant information in
      patients with NSCLC of adenocarcinoma histology. Here we present a short overview
      of the tumor angiogenesis pathways and antiangiogenic drugs. In particular, we
      will focus on nintedanib, from the preclinical studies to the latest phase III
      clinical trial that allowed this new agent to be approved by the European
      Medicines Agency as a second-line treatment option in association with docetaxel
      for NSCLC patients with adenocarcinoma histology. 

PMID- 25855062
TI  - Emetic responses to T-2 toxin, HT-2 toxin and emetine correspond to plasma
      elevations of peptide YY3-36 and 5-hydroxytryptamine.
AB  - Trichothecene mycotoxins are a family of potent translational inhibitors that are
      associated with foodborne outbreaks of human and animal gastroenteritis in which
      vomiting is a clinical hallmark. Deoxynivalenol (DON, vomitoxin) and other Type B
      trichothecenes have been previously demonstrated to cause emesis in the mink
      (Neovison vison), and this response has been directly linked to secretion of both
      the satiety hormone peptide YY3-36 (PYY3-36) and neurotransmitter 5
      hydroxytryptamine (5-HT). Here, we characterized the emetic responses in the mink
      to T-2 toxin (T-2) and HT-2 toxin (HT-2), two highly toxic Type A trichothecenes
      that contaminate cereals, and further compared these effects to those of emetine,
      a natural alkaloid that is used medicinally and also well known to block
      translation and cause vomiting. Following intraperitoneal (IP) and oral exposure,
      all three agents caused vomiting with evident dose-dependent increases in both
      duration and number of emetic events as well as decreases in latency to emesis. T
      2 and HT-2 doses causing emesis in 50 % of treated animals (ED50s) were 0.05 and
      0.02 mg/kg BW following IP and oral administration, respectively, whereas the
      ED50s for emetine were 2.0 and 1.0 mg/kg BW for IP and oral exposure,
      respectively. Importantly, oral administration of all three toxins elicited
      marked elevations in plasma concentrations of PYY3-36 and 5-HT that corresponded
      to emesis. Taken together, the results suggest that T-2 and HT-2 were much more
      potent than emetine and that emesis induction by all three translational
      inhibitors co-occurred with increases in circulating levels of PYY3-36 and 5-HT.

PMID- 25855063
TI  - Patient-specific finite element models to support clinical decisions: A lesson
      learnt from a case study of percutaneous pulmonary valve implantation.
AB  - OBJECTIVES AND BACKGROUND: Patient-specific finite element (FE) simulations were
      used to assess different transcatheter valve devices and help select the most
      appropriate treatment strategy for a patient (17-year-old male) with borderline
      dimensions for Melody(r) percutaneous pulmonary valve implantation (PPVI).
      METHODS AND RESULTS: Patient-specific implantation site morphology was derived
      from cardiovascular magnetic resonance (CMR) images along with the implantation
      site mechanical behavior by coupling systolic/diastolic dimensions and the
      pressure gradient in a linear elastic model, and iterative tuning. In this way,
      the model accounted for the mechanical response not only of the arterial wall,
      but also of the surrounding tissue. Four stents (2 balloon-expandable including
      prestenting and 2 self-expandable) were virtually implanted and the stent final
      configuration, anchoring, migration forces, arterial wall stresses, paravalvular
      regurgitation, and device mechanical performance were evaluated. A Sapien29
      device with prestenting was indicated as the optimal approach for this specific
      patient as it had a fully open valve, safe anchoring along the entire
      circumference, low risk of paravalvular leak, and arterial rupture. However, at
      the time of the PPVI procedure, after balloon sizing, device implantation was
      suspended due to perceived high risk of device embolization. CONCLUSIONS: FE
      analysis allows a comparison between different treatment scenarios to add
      information to the clinical decision making process. However, further studies are
      required to fully predict patient-specific response to stenting and therefore
      true clinical outcomes.

PMID- 25855064
TI  - The cannabis conundrum: Thinking outside the THC box.

PMID- 25855065
TI  - LED-controlled tuning of ZnO nanowires' wettability for biosensing applications.
AB  - BACKGROUND: Wettability is an important property of solid materials which can be
      controlled by surface energy. Dynamic control over the surface wettability is of
      great importance for biosensing applications. Zinc oxide (ZnO) is a biocompatible
      material suitable for biosensors and microfluidic devices. Nanowires of ZnO tend
      to show a hydrophobic nature which decelerates the adhesion or adsorption of
      biomolecules on the surface and, therefore, limits their application. METHODS:
      Surface wettability of the ZnO nanowires can be tuned using light irradiation.
      However, the control over wettability using light-emitting diodes (LEDs) and the
      role of wavelength in controlling the wettability of ZnO nanowires are unclear.
      This is the first report on LED-based wettability control of nanowires, and it
      includes investigations on tuning the desired wettability of ZnO nanowires using
      LEDs as a controlling tool. RESULTS: The investigations on spectral properties of
      the LED emission on ZnO nanowires' wettability have shown strong dependency on
      the spectral overlap of LED emission on ZnO absorption spectra. Results indicate
      that LEDs offer an advanced control on dynamically tuning the wettability of ZnO
      nanowires. CONCLUSION: The spectral investigations have provided significant
      insight into the role of irradiating wavelength of light and irradiation time on
      the surface wettability of ZnO nanowires. This process is suitable to realize on
      chip based integrated sensors and has huge potential for eco-friendly biosensing
      and environmental sensing applications.

PMID- 25855066
TI  - Positive Selection at the Polyhomeotic Locus Led to Decreased Thermosensitivity
      of Gene Expression in Temperate Drosophila melanogaster.
AB  - Drosophila melanogaster as a cosmopolitan species has successfully adapted to a
      wide range of different environments. Variation in temperature is one important
      environmental factor that influences the distribution of species in nature. In
      particular for insects, which are mostly ectotherms, ambient temperature plays a
      major role in their ability to colonize new habitats. Chromatin-based gene
      regulation is known to be sensitive to temperature. Ambient temperature leads to
      changes in the activation of genes regulated in this manner. One such regulatory
      system is the Polycomb group (PcG) whose target genes are more expressed at lower
      temperatures than at higher ones. Therefore, a greater range in ambient
      temperature in temperate environments may lead to greater variability
      (plasticity) in the expression of these genes. This might have detrimental
      effects, such that positive selection acts to lower the degree of the expression
      plasticity. We provide evidence for this process in a genomic region that harbors
      two PcG-regulated genes, polyhomeotic proximal (ph-p) and CG3835. We found a
      signature of positive selection in this gene region in European populations of D.
      melanogaster and investigated the region by means of reporter gene assays. The
      target of selection is located in the intergenic fragment between the two genes.
      It overlaps with the promoters of both genes and an experimentally validated
      Polycomb response element (PRE). This fragment harbors five sequence variants
      that are highly differentiated between European and African populations. The
      African alleles confer a temperature-induced plasticity in gene expression, which
      is typical for PcG-mediated gene regulation, whereas thermosensitivity is reduced
      for the European alleles. 

PMID- 25855067
TI  - Multiplex Conditional Mutagenesis Using Transgenic Expression of Cas9 and sgRNAs.
AB  - Determining the mechanism of gene function is greatly enhanced using conditional
      mutagenesis. However, generating engineered conditional alleles is inefficient
      and has only been widely used in mice. Importantly, multiplex conditional
      mutagenesis requires extensive breeding. Here we demonstrate a system for one
      generation multiplex conditional mutagenesis in zebrafish (Danio rerio) using
      transgenic expression of both cas9 and multiple single guide RNAs (sgRNAs). We
      describe five distinct zebrafish U6 promoters for sgRNA expression and
      demonstrate efficient multiplex biallelic inactivation of tyrosinase and insulin
      receptor a and b, resulting in defects in pigmentation and glucose homeostasis.
      Furthermore, we demonstrate temporal and tissue-specific mutagenesis using
      transgenic expression of Cas9. Heat-shock-inducible expression of cas9 allows
      temporal control of tyr mutagenesis. Liver-specific expression of cas9 disrupts
      insulin receptor a and b, causing fasting hypoglycemia and postprandial
      hyperglycemia. We also show that delivery of sgRNAs targeting ascl1a into the eye
      leads to impaired damage-induced photoreceptor regeneration. Our findings suggest
      that CRISPR/Cas9-based conditional mutagenesis in zebrafish is not only feasible
      but rapid and straightforward. 

PMID- 25855070
TI  - "Angiography without contrast": Severe vascular calcification in chronic kidney
      disease.

PMID- 25855069
TI  - Fine mapping and resequencing of the PARK16 locus in Parkinson's disease.
AB  - The PARK16 locus, spanning five genes on chromosome 1, was among the first
      genetic regions to show genome-wide association in Parkinson's disease (PD).
      Subsequent investigations have found variability in PARK16 top-hits and
      association patterns across populations, and the implicated genes and mechanisms
      are currently unclear. In the present study, we aimed to explore the contribution
      of PARK16 variability to PD risk in a Scandinavian population. We genotyped 17
      single-nucleotide polymorphisms in a case-control sample set of 2570 individuals
      from Norway and Sweden to fine map the locus. Targeted resequencing of the full
      coding regions of SLC45A3, NUCKS1, RAB7L1, SLC41A1 and PM20D1 was performed in
      DNA pools from a subset of 387 patient samples. We find evidence for an
      association with PD for rs1775143 as well as a haplotype located around the 5'
      region of RAB7L1, implicating variants which are not in high linkage
      disequilibrium with the strongest signal from a recent large meta-analysis in
      Caucasians. We also provide suggestive support for epistasis between RAB7L1 and
      LRRK2 as previously hypothesized by others. Comparing our results with previous
      work, allelic heterogeneity at PARK16 appears likely, and further studies are
      warranted to disentangle the complex patterns of association and pinpoint the
      functionally relevant variants. 

PMID- 25855068
TI  - Japan PGx Data Science Consortium Database: SNPs and HLA genotype data from 2994
      Japanese healthy individuals for pharmacogenomics studies.
AB  - Japan Pharmacogenomics Data Science Consortium (JPDSC) has assembled a database
      for conducting pharmacogenomics (PGx) studies in Japanese subjects. The database
      contains the genotypes of 2.5 million single-nucleotide polymorphisms (SNPs) and
      5 human leukocyte antigen loci from 2994 Japanese healthy volunteers, as well as
      121 kinds of clinical information, including self-reports, physiological data,
      hematological data and biochemical data. In this article, the reliability of our
      data was evaluated by principal component analysis (PCA) and association analysis
      for hematological and biochemical traits by using genome-wide SNP data. PCA of
      the SNPs showed that all the samples were collected from the Japanese population
      and that the samples were separated into two major clusters by birthplace,
      Okinawa and other than Okinawa, as had been previously reported. Among 87 SNPs
      that have been reported to be associated with 18 hematological and biochemical
      traits in genome-wide association studies (GWAS), the associations of 56 SNPs
      were replicated using our data base. Statistical power simulations showed that
      the sample size of the JPDSC control database is large enough to detect genetic
      markers having a relatively strong association even when the case sample size is
      small. The JPDSC database will be useful as control data for conducting PGx
      studies to explore genetic markers to improve the safety and efficacy of drugs
      either during clinical development or in post-marketing. 

PMID- 25855071
TI  - Using a novel spatial tool to inform invasive species early detection and rapid
      response efforts.
AB  - Management of invasive species has increasingly emphasized the importance of
      early detection and rapid response (EDRR) programs in limiting introductions,
      establishment, and impacts. These programs require an understanding of vector and
      species spatial dynamics to prioritize monitoring sites and efficiently allocate
      resources. Yet managers often lack the empirical data necessary to make these
      decisions. We developed an empirical mapping tool that can facilitate development
      of EDRR programs through identifying high-risk locations, particularly within the
      recreational boating vector. We demonstrated the utility of this tool in the
      Great Lakes watershed. We surveyed boaters to identify trips among water bodies
      and to quantify behaviors associated with high likelihood of species transfer
      (e.g., not removing organic materials from boat trailers) during that trip. We
      mapped water bodies with high-risk inbound and outbound boater movements using
      ArcGIS. We also tested for differences in high-risk behaviors based on
      demographic variables to understand risk differences among boater groups.
      Incorporation of boater behavior led to identification of additional high-risk
      water bodies compared to using the number of trips alone. Therefore, the number
      of trips itself may not fully reflect the likelihood of invasion. This tool can
      be broadly applied in other geographic contexts and with different taxa, and can
      be adjusted according to varying levels of information concerning the vector or
      species of interest. The methodology is straightforward and can be followed after
      a basic introduction to ArcGIS software. The visual nature of the mapping tool
      will facilitate site prioritization by managers and stakeholders from diverse
      backgrounds. 

PMID- 25855072
TI  - Stormwater management criteria for on-site pollution control: a comparative
      assessment of international practices.
AB  - Over the last decade, a growing interest has been shown toward innovative
      stormwater management practices, breaking away from conventional "end of pipe"
      approaches (based on conveying water offsite to centralized detention
      facilities). Innovative strategies, referred to as sustainable urban drainage
      systems, low impact development (LID) or green infrastructures, advocating for
      management of runoff as close to its origin as possible, have therefore gained a
      lot of popularity among practitioners and public authorities. However, while the
      need for pollution control is generally well accepted, there is no wide agreement
      about management criteria to be given to developers. This article hence aims to
      compare these criteria through literature analysis of different state or local
      stormwater management manuals or guidelines, investigating both their suitability
      for pollution control and their influence on best management practices selection
      and design. Four categories of criteria were identified: flow-rate limitations,
      "water quality volumes" (to be treated), volume reduction (through infiltration
      or evapotranspiration), and non-hydrologic criteria (such as loads reduction
      targets or maximum effluent concentrations). This study suggests that hydrologic
      criteria based on volume reduction (rather than treatment) might generally be
      preferable for on-site control of diffuse stormwater pollution. Nonetheless,
      determination of an appropriate management approach for a specific site is
      generally not straightforward and presents a variety of challenges for site
      designers seeking to satisfy local requirements in addressing stormwater quantity
      and quality issues. The adoption of efficient LID solution may therefore strongly
      depend on the guidance given to practitioners to account for these management
      criteria. 

PMID- 25855074
TI  - Protecting a CT simulator room to accommodate a cyberknife facility.
AB  - In 2012, a plan to develop Stereotactic treatments using a Cyberknife was
      unveiled at the Hermitage Medical Clinic, Dublin. Due to planning restrictions
      the new facility had to be contained in the existing hospital's blue print with
      the only available location being an unused CT simulation room. The room design
      would be different from conventional radiotherapy bunkers due to the fact the
      Cyberknife can fire an unfiltered beam in any direction bar the roof (restriction
      of 22 degrees  above the horizontal). Therefore all walls must be primary
      barriers with the roof designed to protect against the large leakage radiation
      resulting from the high MU's used during the treatments. Space consideration
      indicated that concrete alone could not be used to restrict the radiation beam to
      acceptable limits. To this end a combination of steel, lead, normal and heavy
      concrete were used to meet the dose constraints established by the Irish
      licensing authorities. 

PMID- 25855073
TI  - Effect of intestinal resection on quality of life in Crohn's disease.
AB  - INTRODUCTION: Patients with Crohn's disease have poorer health-related quality of
      life [HRQoL] than healthy individuals, even when in remission. Although HRQoL
      improves in patients who achieve drug-induced or surgically induced remission,
      the effects of surgery overall have not been well characterised. METHODS: In a
      randomised trial, patients undergoing intestinal resection of all macroscopically
      diseased bowel were treated with postoperative drug therapy to prevent disease
      recurrence. All patients were followed prospectively for 18 months. C-reactive
      protein [CRP], Crohn's Disease Activity Index [CDAI], and faecal calprotectin
      [FC] were measured preoperatively and at 6, 12, and 18 months. HRQoL was assessed
      with a general [SF36] and disease-specific [IBDQ] questionnaires at the same time
      points. RESULTS: A total of 174 patients were included. HRQoL was poor
      preoperatively but improved significantly [p < 0.001] at 6 months
      postoperatively. This improvement was sustained at 18 months. Females and smokers
      had a poorer HRQoL when compared with males and non-smokers, respectively.
      Persistent endoscopic remission, intensification of drug treatment at 6 months,
      and anti-tumour necrosis factor therapy were not associated with HRQoL outcomes
      different from those when these factors were not present. There was a significant
      inverse correlation between CDAI, [but not endoscopic recurrence, CRP, or FC] on
      HRQoL. CONCLUSION: Intestinal resection of all macroscopic Crohn's disease in
      patients treated with postoperative prophylactic drug therapy is associated with
      significant and sustained improvement in HRQoL irrespective of type of drug
      treatment or endoscopic recurrence. HRQoL is lower in female patients and
      smokers. A higher CDAI, but not direct measures of active disease or type of drug
      therapy, is associated with a lower HRQoL.

PMID- 25855075
TI  - Evaluation of time-efficient reconstruction methods in digital breast
      tomosynthesis.
AB  - Three reconstruction algorithms for digital breast tomosynthesis were compared in
      this article: filtered back-projection (FBP), iterative adapted FBP and maximum
      likelihood-convex iterative algorithms. Quality metrics such as signal-difference
      to-noise ratio, normalised line-profiles and artefact-spread function were used
      for evaluation of reconstructed tomosynthesis images. The iterative-based methods
      offered increased image quality in terms of higher detectability and reduced
      artefacts, which will be further examined in clinical images. 

PMID- 25855076
TI  - Risk of radiation exposure to medical staff involved in interventional
      endourology.
AB  - The aim is to estimate the possibility the new annual dose limit for eye lens to
      be exceeded and to study the impact of protective shield. Radiation exposure to
      medical personnel was evaluated with EDD-30 dosemeter in positions of operating
      surgeon, assisting doctor and nurse. At the operator's typical position for
      diagnosis and treatment of the urinary tract, the lens dose rates were 0.9 mSv h(
      1) and 0.06 mSv h(-1) without and with lead shield. At the operator's position
      typical for percutaneous intervention dose rates were 1.9 and 0.02 mSv h(-1),
      respectively. At typical workload, the annual eye lens dose to the main operator
      without protective screen was estimated to be 29 mSv. With lead screen, operator
      lens dose can be reduced by a factor of 15-95 according to the procedure.
      Installation and use of lead screen and use of lead glasses were recommended to
      the endourology medical team. 

PMID- 25855077
TI  - Medical exposure assessment: the global approach of the United Nations Scientific
      Committee on the Effects of Atomic Radiation.
AB  - The United Nations Scientific Committee on the Effects of Atomic Radiation
      (UNSCEAR) was established in 1955 to systematically collect, evaluate, publish
      and share data on the global levels and effects of ionizing radiation from
      natural and artificial sources. Regular surveys have been conducted to
      determinate the frequencies of medical radiological procedure, the number of
      equipment and staffing and the level of global exposure using the health care
      level (HCL) extrapolation model. UNSCEAR surveys revealed a range of issues
      relating to participation, survey process, data quality and analysis. Thus,
      UNSCEAR developed an improvement strategy to address the existing deficiencies in
      data quality and collection. The major element of this strategy is the
      introduction of an on-line platform to facilitate the data collection and
      archiving process. It is anticipated that the number of countries participating
      in UNSCEAR's surveys will increase in the future, particularly from HCL II-IV
      countries. 

PMID- 25855078
TI  - Systematic review: the financial burden of surgical complications in patients
      with ulcerative colitis.
AB  - BACKGROUND: Patients undergoing colectomy for ulcerative colitis (UC) may
      experience complications associated with reduced quality of life (QoL), and maybe
      a considerable economic burden to healthcare systems. Appreciation of these
      burdens is important to evaluate the cost effectiveness of newer interventions
      for UC vs. colectomy. AIM: To identify data representing resource utilisation or
      costs of complications arising from colorectal procedures in patients with UC,
      and data representing patient QoL, as reported by health state utility values
      (HSUVs). METHODS: Embase, MEDLINE and The Cochrane Library were searched for
      studies (1995-2014) reporting resource use/costs of surgical complications, and
      HSUVs data in adult patients with UC, undergoing colorectal procedures.
      Conference proceedings (January 2011-January 2014) were hand-searched. RESULTS:
      Twelve studies reported resource use/costs, and three reported HSUVs data in
      patients with UC experiencing surgical complications. Additional mean costs of
      postoperative complications ranged from $18 650/patient with complications at a 6
      month follow-up (46% incidence) to $34 714/patient with complications over a 5
      year period (49% incidence). Pouchitis, pouch failure and small bowel obstruction
      carried the greatest burden. Marked reductions in HSUVs were observed for
      patients with UC experiencing surgical complications, vs. patients with UC in a
      remission state. CONCLUSIONS: There is a paucity of well reported studies on
      resource use/cost, and QoL burden of surgical complications in patients with UC.
      However, surgical complications represent a substantial burden both in terms of
      cost and of quality of life, with reoperations, physician fees, additional in
      patient hospital stays and infertility treatment being the main cost drivers.

PMID- 25855079
TI  - N-glycosylation is essential for ileal ASBT function and protection against
      proteases.
AB  - The bile acid transporter ASBT is a glycoprotein responsible for active
      absorption of bile acids. Inhibiting ASBT function and bile acid absorption is an
      attractive approach to lower plasma cholesterol and improve glucose imbalance in
      diabetic patients. Deglycosylation of ASBT was shown to decrease its function.
      However, the exact roles of N-glycosylation of ASBT, and how it affects its
      function, is not known. Current studies investigated the roles of N-glycosylation
      in ASBT protein stability and protection against proteases utilizing HEK-293
      cells stably transfected with ASBT-V5 fusion protein. ASBT-V5 protein was
      detected as two bands with molecular mass of ~41 and ~35 kDa. Inhibition of
      glycosylation by tunicamycin significantly decreased ASBT activity and shifted
      ASBT bands to ~30 kDa, representing a deglycosylated protein. Treatment of total
      cellular lysates with PNGase F or Endo H glycosidases showed that the upper 41
      kDa band represents a fully mature N-acetylglucosamine-rich glycoprotein and the
      lower 35-kDa band represents a mannose-rich core glycoprotein. Studies with the
      glycosylation deficient ASBT mutant (N10Q) showed that the N-glycosylation is not
      essential for ASBT targeting to plasma membrane. However, mature glycosylation
      significantly increased the half-life and protected ASBT protein from digestion
      with trypsin. Incubating the cells with high glucose (25 mM) for 48 h increased
      mature glycosylated ASBT along with an increase in its function. These results
      unravel novel roles for N-glycosylation of ASBT and suggest that high levels of
      glucose alter the composition of the glycan and may contribute to the increase in
      ASBT function in diabetes mellitus.

PMID- 25855080
TI  - Regulation of NHE3 by lysophosphatidic acid is mediated by phosphorylation of
      NHE3 by RSK2.
AB  - Na(+)/H(+) exchange by Na(+)/H(+) exchanger 3 (NHE3) is a major route of sodium
      absorption in the intestine and kidney. We have shown previously that
      lysophosphatidic acid (LPA), a small phospholipid produced ubiquitously by all
      types of cells, stimulates NHE3 via LPA5 receptor. Stimulation of NHE3 activity
      by LPA involves LPA5 transactivating EGF receptor (EGFR) in the apical membrane.
      EGFR activates proline-rich tyrosine kinase 2 (Pyk2) and ERK, both of which are
      necessary for NHE3 regulation. However, Pyk2 and ERK are regulated by EGFR via
      independent pathways and appear to converge on an unidentified intermediate that
      ultimately targets NHE3. The p90 ribosomal S6 kinase (RSK) family of Ser/Thr
      protein kinases is a known effector of EGFR and ERK. Hence, we hypothesized that
      RSK may be the convergent effector of Pyk2 and ERK although it is not known
      whether Pyk2 regulates RSK. In this study, we show that Pyk2 is necessary for the
      maintenance of phosphoinositide-dependent kinase 1 (PDK1) autophosphorylation,
      and knockdown of Pyk2 or PDK1 mitigated LPA-induced phosphorylation of RSK and
      stimulation of NHE3 activity. Additionally, we show that RSK2, but not RSK1, is
      responsible for NHE3 regulation. RSK2 interacts with NHE3 at the apical membrane
      domain, where it phosphorylates NHE3. Alteration of S663 of NHE3 ablated LPA
      induced phosphorylation of NHE3 and stimulation of the transport activity. Our
      study identifies RSK2 as a new kinase that regulates NHE3 activity by direct
      phosphorylation. 

PMID- 25855082
TI  - Functional characterization of the human facilitative glucose transporter 12
      (GLUT12) by electrophysiological methods.
AB  - GLUT12 is a member of the facilitative family of glucose transporters. The goal
      of this study was to characterize the functional properties of GLUT12, expressed
      in Xenopus laevis oocytes, using radiotracer and electrophysiological methods.
      Our results showed that GLUT12 is a facilitative sugar transporter with substrate
      selectivity: d-glucose >= alpha-methyl-d-glucopyranoside (alpha-MG) > 2-deoxy-d
      glucose(2-DOG) > d-fructose = d-galactose. alpha-MG is a characteristic substrate
      of the Na(+)/glucose (SGLT) family and has not been shown to be a substrate of
      any of the GLUTs. In the absence of sugar, (22)Na(+) was transported through
      GLUT12 at a higher rate (40%) than noninjected oocytes, indicating that there is
      a Na(+) leak through GLUT12. Genistein, an inhibitor of GLUT1, also inhibited
      sugar uptake by GLUT12. Glucose uptake was increased by the PKA activator 8
      bromoadenosine 3',5'-cyclic monophosphate (8-Br-cAMP) but not by the PKC
      activator phorbol-12-myristate-13-acetate (PMA). In high K(+) concentrations,
      glucose uptake was blocked. Addition of glucose to the external solution induced
      an inward current with a reversal potential of approximately -15 mV and was
      blocked by Cl(-) channel blockers, indicating the current was carried by Cl(-)
      ions. The sugar-activated Cl(-) currents were unaffected by genistein. In high
      external K(+) concentrations, sugar-activated Cl(-) currents were also blocked,
      indicating that GLUT12 activity is voltage dependent. Furthermore, glucose
      induced current was increased by the PKA activator 8-Br-cAMP but not by the PKC
      activator PMA. These new features of GLUT12 are very different from those
      described for other GLUTs, indicating that GLUT12 must have a specific
      physiological role within glucose homeostasis, still to be discovered. 

PMID- 25855083
TI  - Review of supplemental views and stress radiography in musculoskeletal trauma:
      lower extremity.
AB  - The standard radiographic series is not always sufficient to diagnose and
      characterize subtle musculoskeletal injuries. Missed or delayed diagnoses can
      negatively affect patient acute morbidity and long-term outcomes. Similarly,
      management based on erroneous diagnoses may lead to unnecessary treatment and
      restrictions. Body-part- or joint-specific supplemental radiographic views and
      stress radiography offer an alternative for further evaluation of subtle injuries
      in specific clinical situations and may obviate the need for the added cost and
      potential ionizing radiation exposure of further cross-sectional imaging.
      Familiarity with these complementary exams allows radiologists to play an
      important role in patient care, as their utilization can improve diagnostic
      accuracy, clarify subtle or uncertain findings, and direct timely patient
      management. This review highlights important supplemental views and stress
      radiographic examinations useful in the evaluation of emergent lower extremity
      musculoskeletal trauma. 

PMID- 25855081
TI  - The Golgi apparatus regulates cGMP-dependent protein kinase I compartmentation
      and proteolysis.
AB  - cGMP-dependent protein kinase I (PKGI) is an important effector of cGMP signaling
      that regulates vascular smooth muscle cell (SMC) phenotype and proliferation.
      PKGI has been detected in the perinuclear region of cells, and recent data
      indicate that proprotein convertases (PCs) typically resident in the Golgi
      apparatus (GA) can stimulate PKGI proteolysis and generate a kinase fragment that
      localizes to the nucleus and regulates gene expression. However, the role of the
      endomembrane system in PKGI compartmentation and processing is unknown. Here, we
      demonstrate that PKGI colocalizes with endoplasmic reticulum (ER), ER-Golgi
      intermediate compartment, GA cisterna, and trans-Golgi network proteins in
      pulmonary artery SMC and cell lines. Moreover, PKGI localizes with furin, a trans
      Golgi network-resident PC known to cleave PKGI. ER protein transport influences
      PKGI localization because overexpression of a constitutively inactive Sar1
      transgene caused PKGI retention in the ER. Additionally, PKGI appears to reside
      within the GA because PKGI immunoreactivity was determined to be resistant to
      cytosolic proteinase K treatment in live cells. The GA appears to play a role in
      PKGI proteolysis because overexpression of inositol 1,4,5-trisphosphate receptor
      associated cGMP kinase substrate, not only tethered heterologous PKGI-beta to the
      ER and decreased its localization to the GA, but also diminished PKGI proteolysis
      and nuclear translocation. Also, inhibiting intra-GA protein transport with
      monensin was observed to decrease PKGI cleavage. These studies detail a role for
      the endomembrane system in regulating PKGI compartmentation and proteolysis.
      Moreover, they support the investigation of mechanisms regulating PKGI-dependent
      nuclear cGMP signaling in the pulmonary vasculature with Golgi dysfunction.

PMID- 25855084
TI  - New applications and perspectives of fast field cycling NMR relaxometry.
AB  - The field cycling NMR relaxometry method (also known as fast field cycling (FFC)
      when instruments employing fast electrical switching of the magnetic field are
      used) allows determination of the spin-lattice relaxation time (T1 ) continuously
      over five decades of Larmor frequency. The method can be exploited to observe the
      T1 frequency dependence of protons, as well as any other NMR-sensitive nuclei,
      such as (2) H, (13) C, (31) P, and (19) F in a wide range of substances and
      materials. The information obtained is directly correlated with the
      physical/chemical properties of the compound and can be represented as a 'nuclear
      magnetic resonance dispersion' curve. We present some recent academic and
      industrial applications showing the relevance of exploiting FFC NMR relaxometry
      in complex materials to study the molecular dynamics or, simply, for
      fingerprinting or quality control purposes. The basic nuclear magnetic resonance
      dispersion features are outlined in representative examples of magnetic resonance
      imaging (MRI) contrast agents, porous media, proteins, and food stuffs. We will
      focus on the new directions and perspectives for the FFC technique. For instance,
      the introduction of the latest Wide Bore FFC NMR relaxometers allows probing, for
      the first time, of the dynamics of confined surface water contained in the macro
      pores of carbonate rock cores. We also evidence the use of the latest field
      cycling technology with a new cryogen-free variable-field electromagnet, which
      enhances the range of available frequencies in the 2D T1 -T2 correlation spectrum
      for separating oil and water in crude oil. Copyright (c) 2015 John Wiley & Sons,
      Ltd. 

PMID- 25855086
TI  - Inhibition of HeLa cells metastasis by bioactive compounds in crocodile
      (Crocodylus siamensis) white blood cells extract.
AB  - Matrix metalloproteinases (MMPs) play a key role in cancer progression, including
      cell invasion, metastasis, cell growth, apoptosis, angiogenesis, and cell
      adhesion. Thus, suppression of the MMPs activities is crucial for inhibiting
      cancer cells metastasis. Herein, bioactive agents from crocodile (Crocodylus
      siamensis) leukocyte extracts (WBCex) showed the anticancer activity with HeLa
      cells and inhibited the migration and invasion process by reducing gelatinases
      (MMP-2, MMP-9) activity and their protein levels. This mechanism is regulated via
      interfering Ras and p38 signal transduction. Moreover, disrupting VEGF and
      integrin-signaling cascade by bioactive agents are the predictable mechanisms
      that cause the decreasing of MMP-2 and MMP-9 activity. Hence, bioactive
      substances in WBCex may play the mode of action similar with MMPs inhibitor due
      to HeLa cell metastasis being suppressed in vitro. (c) 2015 Wiley Periodicals,
      Inc. Environ Toxicol 31: 1329-1336, 2016.

PMID- 25855085
TI  - Trichloroethylene-mediated cytotoxicity in human epidermal keratinocytes is
      mediated by the rapid accumulation of intracellular calcium: Interception by
      naringenin.
AB  - Industrial solvents pose a significant threat to the humankind. The mechanisms of
      their toxicity still remain in debate. Trichloroethylene (TCE) is a widespread
      industrial solvent responsible for severe liver dysfunction, cutaneous toxicity
      in occupationally exposed humans. We utilized an in vitro system of human
      epidermal keratinocyte (HaCaT) cells in this study to avoid complex cell and
      extracellular interactions. We report the cytotoxicity of organic solvent TCE in
      HaCaT and its reversal by a natural flavanone, naringenin (Nar). The cytotoxicity
      was attributed to the rapid intracellular free calcium (Ca(2+)) release, which
      might lead to the elevation of protein kinase C along with robust free radical
      generation, instability due to energy depletion, and sensitization of
      intracellular stress signal transducer nuclear factor kappaB. These effects were
      actually seen to induce significant amount of genomic DNA fragmentation.
      Furthermore, all these effects of TCE were effectively reversed by the treatment
      of Nar, a natural flavanone. Our studies identify intracellular Ca as a unique
      target used by organic solvents in the cytotoxicity and highlight the Ca(2+) ion
      stabilizer properties of Nar. 

PMID- 25855087
TI  - The role of mesoscale meteorology in modulating the (222)Rn concentrations in
      Huelva (Spain)--impact of phosphogypsum piles.
AB  - The combined analysis of (222)Rn activity concentrations and mesoscale
      meteorological conditions at Huelva city (Spain) was addressed in this study to
      understand the potential impact of phosphogypsum piles on the (222)Rn activity
      concentrations registered at this area. Hourly mean data from April 2012 to
      February 2013 registered at two sampling sites (Huelva city and in the background
      station of El Arenosillo, located 27 km to the south-east) have been used in the
      study. The results of the present study showed a large difference in mean radon
      concentrations between the two stations during the sampling period, 6.3 +/- 0.4
      Bq m(-3) at Huelva and 3.0 +/- 0.2 Bq m(-3) at El Arenosillo. The analysis has
      demonstrated that hourly (222)Rn concentrations at Huelva city above 22 Bq m(-3),
      with nocturnal peaks up to 50 Bq/m(3), mainly coincided with the occurrence of a
      pure sea-land breeze cycle. Mesoscale circulations in this region are mainly
      characterized by two patterns of sea-land breeze, pure and non-pure, with the
      phosphosypsum piles directly upstream (south) of the city during the afternoon on
      pure sea-breeze days. The difference between mean (222)Rn activity concentrations
      at Huelva city were 9.9 +/- 1.5 Bq m(-3) for the pure pattern and 3.3 +/- 0.5 Bq
      m(-3) for the non-pure pattern, while in the background station concentrations
      were 3.9 +/- 0.4 Bq m(-3) and 2.8 +/- 0.4 Bq m(-3) respectively. Considering
      these large differences, a detailed analysis of composites and case studies of
      representative sea-land breeze cycles of both types and their impact on (222)Rn
      activity concentration was performed. The results suggested that the presence of
      the phosphogypsum piles was necessary in order to justify the high (222)Rn
      activity concentrations observed at Huelva compared with the background station
      in the afternoons on pure sea breeze days (1.5-2.0 Bq m(-3)). On the other hand,
      large night time differences between the two sites on these days were likely to
      be associated with a combination of shallow density currents travelling down the
      Guadalquivir valley and, again, the presence of phosphogypsum piles. The results
      have demonstrated a significant impact of the phosphogypsum piles on (222)Rn
      activity concentrations in Huelva city during the occurrence of pure sea breeze
      days. 

PMID- 25855088
TI  - Neuroendocrine gastro-enteropancreatic tumors - from eminence based to evidence
      based medicine - A Scandinavian view.
AB  - Neuroendocrine tumors (NETs) comprise a heterogenous group of neoplasms with
      variable clinical expression and progression. The primary tumors most frequently
      occur in the lungs, intestine and the pancreas. The NET incidence is
      approximately 6.1/100,000 per year with a prevalence higher than 35/100,000 per
      year. A NET may be functioning with symptoms related to hormone overproduction or
      non-functioning, not presenting any hormone-related symptoms. From the early
      1980s and onwards, Uppsala University Hospital has contributed significantly to
      diagnosis, just to mention immunohistochemistry, radio-immunoassays for hormones
      and peptides and molecular imaging. On the therapeutic side, treatments with
      cytotoxics as well as biologicals such as, somatostatin analogs and interferons
      have been evaluated. We have furthermore been involved in important phase III
      trials for registration of so called, new targeted agents such as, RADIANT-3 and
      RADIANT-2. Our group were also the first to localize the gene for MEN I on
      chromosome 11 locus q13. Most recent developments have been the establishments of
      new biomarkers such as, olfactory receptor E51E1 as well as micro-RNAs in
      carcinoid tumors of the intestine and lung. A new oncolytic virus, Ad-Vince, for
      treatment of most NETs has been developed and is ready for the clinic.
      Furthermore, we have been involved in establishing Nordic and international
      collaborations. Today, NETs is an area with rapid development and recognized by
      international organizations at conferences, with large attendance. The Nordic
      countries continue to be significant contributors to the field. 

PMID- 25855090
TI  - Co-culturing Chlorella minutissima with Escherichia coli can increase neutral
      lipid production and improve biodiesel quality.
AB  - Lipid productivity and fatty acid composition are important metrics for the
      production of high quality biodiesel from algae. Our previous results showed that
      co-culturing the green alga Chlorella minutissima with Escherichia coli under
      high-substrate mixotrophic conditions enhanced both culture growth and crude
      lipid content. To investigate further, we analyzed neutral lipid content and
      fatty acid content and composition of axenic cultures and co-cultures produced
      under autotrophic and mixotrophic conditions. We found that co-culturing C.
      minutissima with E. coli under high substrate conditions (10 g/L) increased
      neutral lipid content 1.9- to 3.1-fold and fatty acid content 1.5- to 2.6-fold
      compared to equivalent axenic C. minutissima cultures. These same co-cultures
      also exhibited a significant fatty acid shift away from trienoic and toward
      monoenoic fatty acids thereby improving the quality of the synthesized fatty
      acids for biodiesel production. Further investigation suggested that E. coli
      facilitates substrate uptake by the algae and that the resulting growth
      enhancement induces a nitrogen-limited condition. Enhanced carbon uptake coupled
      with nitrogen limitation is the likely cause of the observed neutral lipid
      accumulation and fatty acid profile changes.

PMID- 25855089
TI  - Role of the right dorsal anterior insula in the urge to tic in Tourette syndrome.
AB  - BACKGROUND: The mid-posterior part of the insula is involved in processing bodily
      sensations and urges and is activated during tic generation in Tourette syndrome.
      The dorsal anterior part of the insula, however, integrates sensory and emotional
      information with cognitive valuation and is implicated in interoception. The
      right dorsal anterior insula also participates in urge suppression in healthy
      subjects. This study examined the role of the right dorsal anterior insula in the
      urge to tic in Tourette syndrome. METHODS: Resting-state functional magnetic
      resonance imaging was performed in 13 adult Tourette patients and 13 matched
      controls. The role of the right dorsal anterior insula within the urge-tic
      network was investigated using graph theory-based neural network analysis. The
      functional connectivity of the right dorsal anterior insula was also correlated
      with urge and tic severity. RESULTS: Even though the patients did not exhibit any
      overt tics, the right dorsal anterior insula demonstrated higher connectivity,
      especially with the frontostriatal nodes of the urge-tic network in patients
      compared with controls. The functional connectivity between the right dorsal
      anterior insula and bilateral supplementary motor area also correlated positively
      with urge severity in patients. CONCLUSIONS: These results suggest that the right
      dorsal anterior insula is part of the urge-tic network and could influence the
      urge- and tic-related cortico-striato-thalamic regions even during rest in
      Tourette syndrome. It might be responsible for heightened awareness of bodily
      sensations generating premonitory urges in Tourette syndrome.

PMID- 25855091
TI  - Poly(vinyl alcohol)-Thioxanthone as One-Component Type II Photoinitiator for Free
      Radical Polymerization in Organic and Aqueous Media.
AB  - A novel one-component type II polymeric photoinitiator, poly(vinyl alcohol)
      thioxanthone (PVA-TX), is synthesized by a simple acetalization process and
      characterized. PVA-TX enables photopolymerization of methyl methacrylate and
      acrylamide in both organic and aqueous media. Photopolymerization proceeds even
      in the absence of a co-initiator since PVA-TX possesses both chromophoric and
      hydrogen donating sites in the structure. 

PMID- 25855092
TI  - Pros and cons of feeding the septic intensive care unit patient.
AB  - Sepsis is a common disease seen in critically ill patients. Many patients with
      sepsis are unable to provide nutrition for themselves, and therefore initiating
      artificial nutrition has become part of routine care for these patients. However,
      studies investigating the optimal route, composition, volume, and duration of
      nutrition in critically ill patients with sepsis are lacking. The best
      recommendations have to be extrapolated from studies in heterogeneous populations
      of critically ill patients or in those with syndromes such as acute lung injury
      or acute respiratory distress syndrome (ARDS) where sepsis is a common
      predisposing etiology. In this review, we summarize pertinent studies that inform
      clinical practice on providing artificial nutrition to critically ill patients
      with severe sepsis and make recommendations as to how these studies influence
      clinical care of these patients.

PMID- 25855093
TI  - Total nutrient admixtures (3-in-1): pros vs cons for adults.
AB  - Total nutrient admixture (TNA) is a complete parenteral nutrition (PN)
      formulation composed of all macronutrients, including dextrose, amino acids, and
      intravenous fat emulsions (IVFE), in one bag. The TNA may be safely administered
      to the patient, with all components aseptically compounded and minimal
      administration manipulation required, lending itself to decreases in risks of
      catheter contamination and patient infections. The TNA is compatible and stable
      at recommended concentrations, and since the IVFE is in the TNA, it is infused at
      slower rates, allowing for better fat clearance. The TNA offers convenience of
      administration and a potential cost savings to the healthcare institution both
      directly and indirectly. Unfortunately, the TNA is not without concerns. At low
      macronutrient concentrations (lower than recommended), the formulation is
      compromised. Greater divalent and monovalent cation amounts and increased
      concentrations of phosphate and calcium may destabilize the TNA or result in
      precipitation, respectively. With the addition of IVFE in the TNA, catheter
      occlusion is greater and larger pore size filters are necessary, resulting in
      less microbial elimination. Determining if the implementation of the TNA is
      appropriate for an institution requires a recognition of the advantages and
      disadvantages of the TNA as well as an understanding of the institution's patient
      population and their nutrition requirements. 

PMID- 25855094
TI  - CO(2) and N(2)O emissions in a soil chronosequence at a glacier retreat zone in
      Maritime Antarctica.
AB  - Studies of C cycle alterations are extremely important to identify changes due to
      climate change, especially in the polar ecosystem. The objectives of this study
      were to (i) examine patterns of soil CO2-C and N2O-N emissions, and (ii) evaluate
      the quantity and quality of soil organic matter across a glacier retreat
      chronosequence in the Maritime Antarctica. Field measurements were carried out
      during January and February 2010 (summer season) along a retreating zone of the
      White Eagle Glacier, at King George Island, Maritime Antarctica. Soil samples (0
      10cm) were collected along a 500-m transect at regular intervals to determine
      changes in soil organic matter. Field CO2-C emission measurements and soil
      temperature were carried out at regular intervals. In addition, greenhouse gas
      production potentials were assessed through 100days laboratory incubations. Soils
      exposed for a longer time tended to have greater concentrations of soluble salts
      and possess sandier textures. Total organic C (3.59gkg(-1)), total N (2.31gkg(
      1)) and labile C (1.83gkg(-1)) tended to be lower near the glacier front compared
      with sites away from it, which is correlated with decreasing degree of
      humification of the soil organic matter with exposure time. Soil CO2-C emissions
      tended to increase with distance from the glacier front. On average, the presence
      of vegetation increased CO2-C emissions by 440%, or the equivalent of 0.633g of
      CO2-C m(-2)h(-1). Results suggest that newly exposed landsurfaces undergo soil
      formation with increasing labile C input from vegetation, accompanied by
      increasing soil CO2-C emissions. Despite the importance of exposure time on CO2-C
      production and emissions, there was no similar trend in soil N2O-N production
      potentials as a function of glacial retreat. For N2O, instead, the maximum
      production occurred in sites with the first stages of vegetation growth. 

PMID- 25855096
TI  - Factor XI-related thrombosis and the role of concentrate treatment in factor XI
      deficiency.

PMID- 25855095
TI  - Prevalence and correlates of use of complementary and alternative medicine in
      children with autism spectrum disorder in Europe.
AB  - This study examined the prevalence and correlates of use of complementary and
      alternative medicine (CAM) among a sample of children with autism spectrum
      disorder (ASD) < 7 years in 18 European countries (N = 1,680). Forty-seven
      percent of parents reported having tried any CAM approach in the past 6 months.
      Diets and supplements were used by 25 % of the sample and mind-body practices by
      24 %; other unconventional approaches were used by 25 % of the families, and a
      minority of parents reported having tried any invasive or potentially harmful
      approach (2 %). Parents in Eastern Europe reported significantly higher rates of
      CAM use. In the total sample, children with lower verbal ability and children
      using prescribed medications were more likely to be receiving diets or
      supplements. Concurrent use of high levels of conventional psychosocial
      intervention was significantly associated with use of mind-body practices. Higher
      parental educational level also increased the likelihood of both use of diets and
      supplements and use of mind-body practices. CONCLUSION: The high prevalence of
      CAM use among a sample of young children with ASD is an indication that parents
      need to be supported in the choice of treatments early on in the assessment
      process, particularly in some parts of Europe. WHAT IS KNOWN: * Use of
      complementary and alternative medicine (CAM) in children with autism spectrum
      disorder is common. * In non-EU samples, parents with higher educational level
      and parents of low functioning children are more likely to use CAM with their
      children. What is New: * This study provides the first data on prevalence and
      correlates of use of CAM approaches in a large sample of young children with
      autism in Europe (N = 1,680). * Rates of CAM use were particularly high in
      Eastern Europe and correlates of use varied by type of CAM across Europe.

PMID- 25855097
TI  - Vegetable-based dye-sensitized solar cells.
AB  - There is currently a large effort to improve the performance of low cost
      renewable energy devices. Dye-sensitized solar cells (DSSCs) are emerging as one
      of the most promising low cost photovoltaic technologies, addressing "secure,
      clean and efficient solar energy conversion". Vegetable dyes, extracted from
      algae, flowers, fruit and leaves, can be used as sensitizers in DSSCs. Thus far,
      anthocyanin and betalain extracts together with selected chlorophyll derivatives
      are the most successful vegetable sensitizers. This review analyses recent
      progress in the exploitation of vegetable dyes for solar energy conversion and
      compares them to the properties of synthetic dyes. We provide an in-depth
      discussion on the main limitation of cell performance e.g. dye degradation,
      effective electron injection from the dye into the conduction band of
      semiconducting nanoparticles, such as titanium dioxide and zinc oxide, outlining
      future developments for the use of vegetable sensitizers in DSSCs. We also
      discuss the cost of vegetable dyes and how their versatility can boost the
      advancement of new power management solutions, especially for their integration
      in living environments, making the practical application of such systems
      economically viable. Finally, we present our view on future prospects in the
      development of synthetic analogues of vegetable dyes as sensitizers in DSSCs. 

PMID- 25855099
TI  - NSAID-exacerbated respiratory disease: a meta-analysis evaluating prevalence,
      mean provocative dose of aspirin and increased asthma morbidity.
AB  - BACKGROUND: The prevalence and mean provocative dose of oral aspirin (MPDA)
      triggering respiratory reactions in people with asthma have been inconsistently
      reported, and the relationship between NSAID-exacerbated respiratory disease
      (NERD) and asthma morbidity was less well quantified. METHODS: A systematic
      review was performed by identifying studies diagnosing NERD using blinded,
      placebo-controlled oral provocation challenge tests (OPCTs) or by self-reported
      history in people with asthma. Data were extracted, and effect estimates for
      changes in respiratory function, MPDA and asthma morbidity were pooled using
      random-effects meta-analysis. RESULTS: The prevalence of NERD in adults with
      asthma was 9.0% (95% CI 6-12%) using OPCTs and 9.9% (95% CI 9.4-10.5%) using self
      reported history from questionnaires. The MPDA in adults with NERD was 85.8 mg
      (95% CI 73.9-97.6). In people with NERD, the risk of: uncontrolled asthma was
      increased twofold (RR 1.96 (95% CI 1.25-3.07)); severe asthma and asthma attacks
      was increased by 60% (RR 1.58 (95% CI 1.15-2.16) and RR 1.59 (95% CI 1.21-2.09),
      respectively); emergency room visits was increased by 80% (RR 1.79 (95% CI 1.29
      2.49)); and asthma hospitalization was increased by 40% (RR 1.37 (95% CI 1.12
      1.67)) compared to people with NSAID-tolerant asthma. CONCLUSIONS: Respiratory
      reactions triggered by oral aspirin in people with asthma are relatively common.
      At the population level, the prevalence of NERD was similar when measured using
      appropriately conducted OPCTs or by self-reported history. On average,
      respiratory reactions were triggered by clinically relevant doses of oral
      aspirin. Asthma morbidity was significantly increased in people with NERD who
      potentially require more intensive monitoring and follow-up.

PMID- 25855100
TI  - Predictors for early diagnosis of cerebral palsy from national registry data.
AB  - AIM: As early intervention is important in cerebral palsy (CP), an early
      diagnosis is desirable. The aim of this study was to establish the median
      diagnostic age of CP and to identify predictors of an early diagnosis in a
      population-based cohort. METHOD: Using the Danish National Cerebral Palsy
      Registry (NCPR), we identified 1291 children with CP (764 males, 527 females)
      born between 1995 and 2003. The date of diagnosis was defined as the day the
      parents were told that their child was spastic or had CP. We calculated the age
      of diagnosis and analysed the following predictors: type of CP, degree of motor
      disability, cerebral ultrasonography results, epilepsy, gestational age, and
      degree of cognitive impairment. RESULTS: We found the overall median corrected
      diagnostic age of CP to be 11 months. Early diagnosis was associated with the
      type of CP, presence of epilepsy, a high degree of motor disability, and
      abnormalities in the cerebral ultrasonography. The gestational age was not
      associated with the diagnostic age. INTERPRETATION: The median diagnostic age
      implies that half of the Danish children with CP will be able to enter an early
      intervention program before 1 year of age. A late diagnosis was associated with
      less severe symptoms, and gestational age did not influence the diagnostic age.

PMID- 25855102
TI  - Impact of sex in stroke thrombolysis: a coarsened exact matching study.
AB  - BACKGROUND: It is not established whether sex influences outcome and safety
      following intravenous thrombolysis (IVT) in acute stroke. As a significant
      imbalance exists between the baseline conditions of women and men, regression
      analysis alone may be subject to bias. Here we aimed to overcome this methodical
      shortcoming by balancing both groups using coarsened exact matching (CEM) before
      evaluating outcome. METHODS: From our local prospective stroke database we
      analyzed consecutive patients who suffered anterior circulation stroke and
      received IVT from 1998 to 04/2013 (n = 1391, 668 female, 723 male). Data were
      preprocessed by CEM, balancing for age, NIHSS, lesion side, hypertension,
      diabetes, atrial fibrillation, smoking, coronary heart disease, and previous
      stroke, which yielded a matched cohort of 502 women and 436 men (n = 938).
      Outcome was estimated by adjusted binomial logistic regression analysis
      incorporating matched weights. RESULTS: No effect of sex was seen to predict good
      outcome (OR 1.04, CI 0.76-1.43) or mortality (OR 1.13, CI 0.73-1.73). However,
      female sex was a strong independent predictor of symptomatic intracerebral
      hemorrhage (sICH - ECASS-II definition, OR 3.62, CI 1.77-7.41) and fatal ICH (OR
      4.53, CI 1.61-12.7). CONCLUSION: In balanced groups, the two sexes showed
      comparable outcomes following IVT. A novel finding was the higher rate of sICH
      and fatal ICH in women. In this analysis we also demonstrate how CEM can reduce
      multivariate imbalance and thereby improve estimates, already in crude, but more
      importantly, in adjusted regression analysis. Further investigations of
      multicentre data with improved analytical approaches that yield balanced sex
      groups are therefore warranted.

PMID- 25855103
TI  - Optical writing and reading with a photoactivatable carbazole.
AB  - The fluorescence of a carbazole chromophore can be activated irreversibly under
      optical control with the photoinduced opening of an oxazine ring. In proximity to
      silver nanoparticles, the quantum efficiency of this photochemical transformation
      and that of the emissive process increase significantly. The plasmonic effects
      responsible for such enhancements, together with the photochemical and
      photophysical properties engineered into this particular photoactivatable
      fluorophore, permit the optical writing and reading of microscaled patterns at
      low illumination intensities. 

PMID- 25855104
TI  - Traumatic spinal cord injury in Nepal.

PMID- 25855098
TI  - Transcriptional selectors, masters, and combinatorial codes: regulatory
      principles of neural subtype specification.
AB  - The broad range of tissue and cellular diversity of animals is generated to a
      large extent by the hierarchical deployment of sequence-specific transcription
      factors and co-factors (collectively referred to as TF's herein) during
      development. Our understanding of these developmental processes has been
      facilitated by the recognition that the activities of many TF's can be
      meaningfully described by a few functional categories that usefully convey a
      sense for how the TF's function, and also provides a sense for the regulatory
      organization of the developmental processes in which they participate. Here, we
      draw on examples from studies in Caenorhabditis elegans, Drosophila melanogaster,
      and vertebrates to discuss how the terms spatial selector, temporal selector,
      tissue/cell type selector, terminal selector and combinatorial code may be
      usefully applied to categorize the activities of TF's at critical steps of
      nervous system construction. While we believe that these functional categories
      are useful for understanding the organizational principles by which TF's direct
      nervous system construction, we however caution against the assumption that a
      TF's function can be solely or fully defined by any single functional category.
      Indeed, most TF's play diverse roles within different functional categories, and
      their roles can blur the lines we draw between these categories. Regardless, it
      is our belief that the concepts discussed here are helpful in clarifying the
      regulatory complexities of nervous system development, and hope they prove useful
      when interpreting mutant phenotypes, designing future experiments, and
      programming specific neuronal cell types for use in therapies.

PMID- 25855105
TI  - Outcomes of transurethral resection of the prostate in benign prostatic
      hyperplasia comparing prostate size of more than 80 grams to prostate size less
      than 80 grams.
AB  - BACKGROUND: Benign prostatic hyperplasia is a condition occurring in elderly men
      in which the prostate gland is enlarged, hence the condition also known as benign
      enlargement of prostate. Benign hyperplasia can lead to both obstructive and
      irritative symptoms. Transurethral resection of prostate (TURP) still remains the
      gold standard modality of surgical treatment of obstructive lower urinary tract
      symptoms due to Benign hyperplasia. OBJECTIVES: The objective of this study was
      to evaluate the outcomes of TURP in large prostate (>80 grams) in comparison to
      small prostate (<80 grams) in terms of efficacy, safety and complications.
      METHODS: A total of 65 cases included in this prospective study, which were
      operated by a single surgeon with conventional monopolar TURP using standard
      technique. Intra -operative and post-operative complications, pre and post-
      operative quality of life (QoL) and international prostate symptom score (IPSS),
      operative time, time to removal of catheter and hospital stay were evaluated
      between small and large prostate gland volumes. RESULTS: Out of 65 cases, 30 were
      with large prostate size i.e. 80 grams or more (group 1), and 35 cases were with
      small prostate size than 80 grams size (group 2). Mean age was 71.8 SD +/- 6.9
      years in group 1 and 68.2 SD +/- 12.7 years in group 2. The mean preoperative
      volume of prostate was 88.8 grams (range 80-115 grams) in group 1 and 40.3 (range
      20-65 grams) in group 2. The mean preoperative post void residual volume of urine
      (PVRU) was 244 ml SD +/- 190.8 ml in group 1 and 117 ml +/- 70.3 ml in group 2.
      Mean resection time in group 1 was 110 (range 90-130) minutes and in group 2 it
      was 90 minutes (range 55-115) minutes. There were quite satisfactory improvements
      in IPSS and QoL. No significant complications were observed except TUR syndrome
      in 2 cases from group 2, which were managed well in postoperative period.
      CONCLUSION: With meticulous resection and intra-operative haemostasis using
      continuous out flow resectoscope, conventional monopolar TURP is equally safe and
      effective in large size prostate as compare in small size.

PMID- 25855106
TI  - Movement disability: situations and factors influencing access to health services
      in the northeast of Thailand.
AB  - BACKGROUND: Persons with movement disability (PWMDs) are the biggest group of
      persons with disabilities (PWDs) with needs helps especially on health. There has
      been no evident to show health services accessibility situation of PWMDs in the
      Northeast of Thailand, the biggest region. OBJECTIVE: This study aimed to explore
      the current situation of accessibility to health services among PWMDs, and
      factors influencing such access. METHOD: This cross-sectional study used a
      multistage stratified random sampling to select 462 subjects from the national
      registered PWMDs poll to response to a structured questionnaire. This study
      complies with the principles of the Declaration of Helsinki and was approved by
      the Khon Kaen University Ethics Committee for Human Research prior to the data
      collection. RESULT: We found that most of PWMDs (66%) had overall health service
      accessibility at medium level. Factors influencing the access to health services
      were living in rural area (adj. mean diff.= -24.01; 95 % CI: -45.88 to-2.31; p
      value=0.032), high income (adj. mean diff.=0.002; 95 % CI: 0.001 to 0.005; p
      value = 0.044), and having offspring or spouse as care givers (adj. mean
      diff.=40.44; 95% CI: 7.69 to 73.19; p-value=0.044; and adj. mean diff.=48.99;
      95%CI: 15.01-82.98; p-value=0.016, respectively). PWMDs who lived in rural areas
      had better access to health services especially to the subdistrict health
      promoting hospital than those in the urban area. CONCLUSION: Accessibly to health
      services of PWMDs still limited. Income, care givers and residential areas had
      influences on their access.

PMID- 25855107
TI  - Modifiable demographic factors that differentiate bronchiolitis from pneumonia in
      Nepalese children less than two years - a hospital based study.
AB  - BACKGROUND: Bronchiolitis and pneumonia is an important cause of mortality and
      morbidity in children. Various risk factors make these children more prone for
      this illness. There is limited data on the risk factors from this part of the
      world. Moreover there is a significant clinical overlap between bronchiolitis and
      pneumonia thus necessitating the need for evaluating their demographic
      difference. OBJECTIVE: To evaluate the modifiable demographic risk factors for
      bronchiolitis and pneumonia in children less than 2 years. METHOD: A prospective,
      comparative hospital based study undertaken during March 2012- March 2013 in
      Manipal Teaching Hospital, Pokhara. Altogether 200 cases of bronchiolitis and 200
      cases of pneumonia, in the age group of 2 to 24 months, were randomly selected
      for comparison of risk factors as per a predesigned proforma. A 'p' value of <
      0.05 was considered statistically significant. Data was analyzed by using SPPS
      version 16. RESULT: The significant risk factors for bronchiolitis were age <6
      months (p<0.001), prematurity (p<0.001),male(P<0.04), younger maternal age
      (p<0.009), poor maternal knowledge (p<0.013), air pollution and lack of
      ventilation (p<0.001), exposure to cooking fuel - kerosene (p<0.007), firewood
      (p<0.001) , tobacco smoke (p<0.001), overcrowding (0.008), winter season
      (p<0.015), domestic pets (p<0.003), low birth weight (p<003), use of animal milk
      (p<0.001).The significant risk factors for pneumonia were age 13 months- 24
      months, maternal age 26- 35 yrs (p<0.009), female (p< 0.04), malnutrition, lack
      of Vitamin A supplementation and immunization (p<0.001). CONCLUSION: Most of the
      risk factors for bronchiolitis and pneumonia identified in this study were
      modifiable; hence could be prevented to decrease the burden of both the diseases.

PMID- 25855108
TI  - Prevalence of Peripheral Arterial Disease (PAD) in End Stage Renal Disease (ESRD)
      Patients on Hemodialysis: a study from central Nepal.
AB  - BACKGROUND: Peripheral arterial disease is a common condition in the hemodialysis
      population with an estimated prevalence ranging from 17-48%. Many studies have
      been conducted to know the prevalence of peripheral vascular disease in
      hemodialysis population. However no such study has been conducted so far in
      Nepal. OBJECTIVE: This study was carried out with an objective to assess the
      prevalence of Peripheral Arterial Disease in End Stage Renal Disease Patients on
      Hemodialysis. METHOD: Fifty patients with a diagnosis of End Stage Renal Disease
      (irrespective of the underlying cause), and those who were on hemodialytic
      support for more than 3 months were studied over a period of one year. Peripheral
      arterial disease was diagnosed on the basis of the ankle -brachial index, which
      was the ratio of the resting systolic blood pressure in the arteries of the ankle
      to that of the brachial artery, measured by using a standard mercury manometer
      with a cuff of appropriate size and the Doppler ultrasound. Patients with ankle 
      brachial index <=0.9 were considered positive for peripheral arterial disease.
      RESULT: A total of 50 End Stage Renal Disease patients were analyzed. The mean
      age of the patient was 49.81+/-12.63 years. The age range was from 18- 79 years.
      Majority of them were males 64% (n=32). Peripheral arterial disease defined by
      ankle -brachial index <= 0.9 was present in 30% (n=15) of patients. The three
      major cause of End Stage Renal Disease in the study population was Chronic
      Glomerulonephritis 40 % (n=20), Type 2 Diabetes Mellitus 28 % (n=14) and
      Hypertension 24 % (n=12). Type 2 Diabetes Mellitus was the commonest cause 53%
      (n=8) of End Stage Renal Disease in patients with peripheral arterial disease
      followed by hypertension 33% (n=5). On univariate analysis, peripheral arterial
      disease was found to be significantly associated with age > 40 years (p value=
      0.003; OR=14.8; CI=1.75-125.27), Type 2 Diabetes Mellitus (p value= 0.009;
      OR=5.4; CI=1.44-21.14), parasthesia of lower limbs (p value= 0.001; OR=10; CI
      2.31-43.16), and intact PTH >300 ng/ml (p value =0.006; OR=5.7; CI=1.55-21.50).
      However on multivariate analysis only parasthesia of lower limbs and intact PTH
      >300 ng/ml were significantly and independently associated with peripheral
      arterial disease, while other variables were not significant. CONCLUSION:
      Peripheral arterial disease was common occurrence in End Stage Renal Disease
      patients on hemodialysis. Ankle -brachial index needs to be included as a routine
      assessment in End Stage Renal Disease patients to detect peripheral arterial
      disease at its earliest.

PMID- 25855109
TI  - A randomized trial of hospital vs home self administration of vaginal misoprostol
      for medical abortion.
AB  - BACKGROUND: A combination of mifepristone followed after 24 hrs by misoprostol
      has proved a safe and effective abortifacient for termination of early pregnancy.
      Home use of misoprostol for medical abortion is still controversial in many
      countries including ours where women's literacy rate is low. Particularly in
      developing countries, this method markedly decreased the hospital visit which
      would be beneficial to patients and hospital staff. OBJECTIVE: To see whether the
      home self administration of vaginal misoprostol was equally effective as
      administered by trained staff in terms of successful termination of early
      pregnancy. Secondary outcomes were bleeding and pain duration during medical
      abortion, side effects, reason for termination of pregnancy and women's
      acceptability of the procedure. METHOD: One hundred and eighty eight women
      requesting medical abortion with pregnancy less than 63 days gestation were
      randomized into two groups either self administration of vaginal misoprostol (800
      mcg) at home or hospital administration 24 hours after oral 200 mg mifepristone.
      Ultrasound was performed after 14 days to confirm complete abortion. RESULT: The
      overall success rate was similar in two groups: 89.13% on home group Vs 86.9% in
      hospital group. Eleven out of 18 women (61.1%) having incomplete abortion had
      successful termination after 2nd dose misoprostol( 400 mcg). None of the women
      had continued pregnancy. Multigravida had slightly higher risk of failure (R.R:
      1.04). CONCLUSION: Home self administration of vaginal misoprostol was safe and
      effective for early termination of medical abortion and was acceptable. Use of
      extra dose of misoprostol has advantage of higher completion rate of abortion.

PMID- 25855110
TI  - Analysis of consecutive open surgeries for varicose vein at Dhulikhel hospital.
AB  - BACKGROUND: Varicose veins are prominent dilated veins in the lower limb
      primarily due to disease in the junction between superficial and deep venous
      system. Operative treatment of such condition significantly improves quality of
      life and also demonstrably decreases the potential complications. We present with
      analysis of fifty one consecutive open surgeries for varicose vein at Dhulikhel
      Hospital. OBJECTIVE: To analyze consecutive open surgeries for varicose vein in
      terms of gender, age, presenting complaints, findings and post operative
      outcomes. METHOD: All the cases posted for open surgeries for varicose vein at
      Dhulikhel Hospital during September 2012 - July 2013 were included. If great
      saphenous vein in thigh was more than 3 mm, segmental stripping was done. The
      collected data was analyzed using SPSS version 13.0. RESULT: There were 51 cases
      with 47% male and 53% female. Mean age was 48.9 years. Prominent dilated vein was
      the most common presenting complaints. Incompetent saphenofemoral junction was
      present in 68.6% cases. Segmental stripping was done in 51% cases. Mean days of
      admission was 2.6 days. Mean pain free day was on 3.2 days. In an average,
      patient were able to walk normally in 4.1 days. Analysis of hospital admission
      days, ability to walk normally and pain free day attained in between stripping
      required and stripping not required group showed significant difference with
      higher values in stripping required group. CONCLUSION: Although conventional
      stripping surgery has long been performed for varicose vein, this is associated
      with prolonged hospital admission, prolonged time required for ability to walk
      normally, and prolonged time taken for pain free status. Hence newer modalities
      of treatment like radiofrequency ablation is warranted in our setup too.

PMID- 25855111
TI  - Intraoperative complications of high volume sutureless cataract surgery in Nepal:
      a prospective study.
AB  - BACKGROUND: With high backlog of cataract blindness in the developing countries
      sutureless high volume cataract surgery is preferred surgical technique.
      OBJECTIVE: To report the intraoperative complications of high volume sutureless
      cataract surgery at secondary level eye care centre of Nepal. METHOD: This
      prospective study consisting 1087 eyes that underwent manual small incision
      cataract surgery from 2nd to 28th December 2007 at Shree Janaki Eye Hospital,
      Janakpur, Nepal and operated by a single eye surgeon. Preoperative and
      postoperative ocular findings together with intraoperative complications were
      carefully noted in every individual case. At post operative day one each patient
      was examined including uncorrected visual acuity and post operative complications
      which were subsequently recorded in Performa. Data were analysed using SPSS 11.5.
      RESULT: Sixty-three eyes (5.8%) of 1087 eyes developed intraoperative
      complications. Out of 63 eyes that had intra operative complications, posterior
      capsular rupture were seen in 42 (3.9%), sclera corneal tunnel suturing in 12
      eyes (1.1%), iridodialysis 5 eyes (0.5%) and Descemet stripping in 4 eyes (0.4%).
      62.1% of patients attained uncorrected visual acuity 6/18 or better and in 91.7%
      of eyes, there were no post operative complications. CONCLUSION: High volume
      suture less cataract surgery is safe surgery and should be continue in developing
      countries to achieve the goal of vision 2020, where there is huge backlog of
      cataract blindness.

PMID- 25855112
TI  - Acceptance of family planning amongst patients attending Dhulikhel hospital
      obstetrics and gynecology department.
AB  - BACKGROUND: Knowledge of contraceptive methods is an important factor for an
      individual to use or not use of family planning methods. In Nepal, at least one
      modern method of family planning is universal amongst both men and women.
      OBJECTIVES: To assess the knowledge, attitude regarding various family planning
      methods and practice of contraceptives amongst couples attending Dhulikhel
      Hospital Obstetrics and Gynecology Department. METHODS: Five hundred and fifteen
      couples were interviewed. Their knowledge, attitude and practice of contraception
      were evaluated with the help of pre-evaluated questionnaire. The other variable
      used were the age of the couple, parity, educational status and economic status
      having effect on the contraceptive acceptance were taken into consideration.
      Descriptive analysis was conducted to obtain percentages. RESULTS: We observed
      that 74.98% of women were in the age group of 20-29 years and 59.22% of men were
      within the age group of 20-29 years. Teen age mothers were 17.86% and teen age
      fathers were 1.35%. In our study, we observed that higher the educational level
      better was the acceptance for family planning methods. The higher income group
      had less number of children compared to lesser income group. In our study, we
      noticed that all the couples knew about different methods of family planning,
      main sources of information were television, pamphlets and healthworkers. Only 16
      males had undergone vasectomy and 32 women had undergone tubectomy. Fewer number
      of vasectomy was due to the belief that undergoing vasectomy will make the male
      partner weak physically. 13.20% of women preferred Depot medroxy progesterone as
      a temporary method of family planning, 13% of males preferred condom as a
      temporary method of family planning. CONCLUSION: We conclude that education plays
      a vital role in the acceptance of family planning. As couples who have higher
      education level tend to have higher income and they have lesser number of
      children. They are more receptive towards counseling and agree upon the various
      methods of family planning. The easy accessibility to the various media like
      radio, television tend to make people aware of various methods of family
      planning.

PMID- 25855113
TI  - Clinical profile of patients with recurrent seizure in tertiary care hospital in
      Nepal.
AB  - BACKGROUND: Epilepsy is a common and diverse disorder with many different causes.
      Outcomes are varied with 60-70% of newly diagnosed people rapidly entering
      remission after starting treatment and 20-30% developing a drug-resistant
      epilepsy with consequent clinical and psychosocial distress. About one third of
      patients with a first unprovoked seizure will have further seizures within five
      years, and about three quarters of those with two or three unprovoked seizures
      have further seizures within four years. OBJECTIVE: The aim of the study was to
      find out those factors which were associated with recurrence of seizure in
      Nepalese population. METHOD: It is a Descriptive Cross-sectional study which was
      conducted in Tribhuvan University Teaching Hospital from January 2013 to January
      2014. RESULT: A total of 150 patients participated in the study. Neuroimaging was
      normal in 65(43.3%) patients. 48(32%) patients had neurocystercosis in their
      brain imaging, neuroinfection in 12(8%) of cases, cerebral infarction in 12(8%),
      Cerebral atrophy in 5(3.3%) patients, brain tumor in 4(2.7%), Mesial temporal
      sclerosis in 2(1.3%), tuberous sclerosis in 1(0.7%) and hypoxic brain injury in 1
      (0.7%) patient. 14(9.3%) patients reported having a family history of epilepsy in
      first degree relative. There was statistically significant association between
      higher number of seizures before starting medication and increased frequency of
      seizure after starting medication (p<0.001). CONCLUSION: Most of the patients
      with recurrent seizure had identifiable cause. Neurocysticercosis was the most
      common cause. Higher number of seizure before starting medication was associated
      with increased frequency of seizure after starting medication.

PMID- 25855114
TI  - Class III subdivision malocclusion with unilateral posterior crossbite.
AB  - This article describes the management of class III subdivision malocclusion with
      unilateral left side posterior crossbite in an adolescent girl, using rapid
      palatal expansion followed by extraction of four premolars with comprehensive
      fixed appliance mechanotherapy. 

PMID- 25855115
TI  - Cervical capillary haemangioma: a case report.
AB  - Capillary haemangioma is a common benign lesion occurring at multiple areas of
      body. They have unique radiological appearances and are confirmed by histological
      examinations. However capillary haemangioma of cervical region is a very rare
      condition. Such a case is presented here. It presented as an extramedullary
      intradural mass compressing the cord and corresponding root giving rise to
      myeloradiculopathic symptoms. Total enblock excision of the lesion gave a total
      cure. 

PMID- 25855116
TI  - Gingival calcifying epithelial tumor - a rare case report.
AB  - Calcifying epithelial odontogenic tumors are rare odontogenic neoplasms that
      account for approximately one percent of all odontogenic tumors. Extra osseous
      variant is very rare with very few cases being reported in literature Peripheral
      Calcifying epithelial odontogenic tumor (CEOT) commonly resemble oral
      hyperplastic or reactive lesions and are histologically similar to their
      intraosseous counterparts. Here we report a rare case of gingival calcifying
      epithelial odontogenic tumor in the mandibular posterior region in a 31 year old
      female patient. Interestingly on literature review in on PubMed search only 22
      case reports were available in, English literature, added to that this report
      will be the 23rd case. 

PMID- 25855117
TI  - Leiomyoma of broad ligament mimicking ovarian malignancy- report of a unique
      case.
AB  - Tumors of the broad ligament are uncommon. Leiomyoma, which is the commonest
      female genital neoplasm, is also the most common solid tumor of the broad
      ligament. Leiomyomas affect 30% of all women of reproductive age but the
      incidence of broad-ligament leiomyoma is <1%. These benign tumors are usually
      asymptomatic. A case is being described where a 52 year old presented with
      gradual abdominal swelling which was clinically and radiologically diagnosed as
      ovarian malignancy. On abdominal and bimanual palpation a soft cystic mass was
      noted in the right pelvic region. CA 125 was mildly raised. CEA, CA 19.9 levels
      were within normal limit. The radiological diagnosis was ovarian cyst with
      possibility of malignant changes. Staging laparotomy and histopathological
      examination of the resected specimen revealed a right sided broad ligament
      leiomyoma with cystic changes. The degenerative changes in the leiomyoma lead to
      the clinical and radiological diagnostic confusion. Thus, though uncommon, broad
      ligament leiomyoma should be considered during evaluation of adnexal masses for
      optimal patient management. The above description of leiomyoma in the broad
      ligament is a highly unique case and thus deserves appropriate attention. 

PMID- 25855118
TI  - Review, evaluation, and discussion of the challenges of missing value imputation
      for mass spectrometry-based label-free global proteomics.
AB  - In this review, we apply selected imputation strategies to label-free liquid
      chromatography-mass spectrometry (LC-MS) proteomics datasets to evaluate the
      accuracy with respect to metrics of variance and classification. We evaluate
      several commonly used imputation approaches for individual merits and discuss the
      caveats of each approach with respect to the example LC-MS proteomics data. In
      general, local similarity-based approaches, such as the regularized expectation
      maximization and least-squares adaptive algorithms, yield the best overall
      performances with respect to metrics of accuracy and robustness. However, no
      single algorithm consistently outperforms the remaining approaches, and in some
      cases, performing classification without imputation sometimes yielded the most
      accurate classification. Thus, because of the complex mechanisms of missing data
      in proteomics, which also vary from peptide to protein, no individual method is a
      single solution for imputation. On the basis of the observations in this review,
      the goal for imputation in the field of computational proteomics should be to
      develop new approaches that work generically for this data type and new
      strategies to guide users in the selection of the best imputation for their
      dataset and analysis objectives. 

PMID- 25855119
TI  - Dietary arginine requirements for growth are dependent on the rate of citrulline
      production in mice.
AB  - BACKGROUND: In many species, including humans, arginine is considered a
      semiessential amino acid because under certain conditions endogenous synthesis
      cannot meet its demand. The requirements of arginine for growth in mice are ill
      defined and seem to vary depending on the genetic background of the mice.
      OBJECTIVE: The objective of this study was to determine the metabolic and
      molecular basis for the requirement of arginine in 2 mouse strains. METHODS:
      Institute of Cancer Research (ICR) and C57BL/6 (BL6) male mice were fed arginine
      free or arginine-sufficient diets (Expt. 1) or 1 of 7 diets with increasing
      arginine concentration (from 0- to 8-g/kg diet, Expt. 2) between day 24 and 42 of
      life to determine the arginine requirements for growth. Citrulline production and
      "de novo" arginine synthesis were measured with use of stable isotopes, and
      arginine requirements were determined by breakpoint analysis and enzyme
      expression by reverse transcriptase-polymerase chain reaction. RESULTS: In Expt.
      1, ICR mice grew at the same rate regardless of the arginine concentration of the
      diet (mean +/- SE: 0.66 +/- 0.04 g/d, P = 0.80), but BL6 mice had a reduced
      growth rate when fed the arginine-free diet (0.25 +/- 0.02 g/d, P < 0.001)
      compared to the 8-g arginine/kg diet (0.46 +/- 0.03 g/d). ICR mice showed at
      least a 2-fold greater expression (P < 0.001) of ornithine transcarbamylase (OTC)
      than BL6 mice, which translated into a greater rate of citrulline (25%) and
      arginine synthesis (49%, P < 0.002). In Expt. 2, breakpoint analysis showed that
      the requirement for growth of BL6 mice was met with 2.32 +/- 0.39 g arginine/kg
      diet; for ICR mice, however, no breakpoint was found. CONCLUSION: Our data
      indicate that a reduced expression of OTC in BL6 mice translates into a reduced
      production of citrulline and arginine compared with ICR mice, which results in a
      dietary arginine requirement for growth in BL6 mice, but not in ICR mice.

PMID- 25855120
TI  - A Dual-Carbon-and-Nitrogen Stable Isotope Ratio Model Is Not Superior to a Single
      Carbon Stable Isotope Ratio Model for Predicting Added Sugar Intake in Southwest
      Virginian Adults.
AB  - BACKGROUND: An objective measure of added sugar (AS) and sugar-sweetened beverage
      (SSB) intake is needed. The delta(13)C value of finger-stick blood is a novel
      validated biomarker of AS/SSB intake; however, nonsweetener corn products and
      animal protein also carry a delta(13)C value similar to AS sources, which may
      affect blood delta(13)C values. The delta(15)N value of blood has been proposed
      as a "correction factor" for animal protein intake. OBJECTIVES: The objectives
      were to 1) identify foods associated with delta(13)C and delta(15)N blood values,
      2) determine the contribution of nonsweetener corn to the diet relative to AS
      intake, and 3) determine if the dual-isotope model (delta(13)C and delta(15)N) is
      a better predictor of AS/SSB intake than delta(13)C alone. METHODS: A cross
      sectional sample of southwest Virginian adults (n = 257; aged 42 +/- 15 y; 74%
      overweight/obese) underwent dietary intake assessments and provided finger-stick
      blood samples, which were analyzed for delta(13)C and delta(15)N values by using
      natural abundance stable isotope mass spectrometry. Statistical analyses included
      ANOVAs, paired-samples t tests, and multiple linear regressions. RESULTS: The
      mean +/- SD daily AS intake was 88 +/- 59 g and nonsweetener corn intake was 13
      +/- 13 g. The mean delta(13)C value was -19.1 +/- 0.90/00, which was
      significantly correlated with AS and SSB intakes (r = 0.32 and 0.39,
      respectively; P <= 0.01). The delta(13)C value and nonsweetener corn intake and
      the delta(15)N value and animal protein intake were not correlated. AS intake was
      significantly greater than nonsweetener corn intake (mean difference = 76.2 +/-
      57.2 g; P <= 0.001). The delta(13)C value was predictive of AS/SSB intake (beta
      range: 0.28-0.35; P <= 0.01); however, delta(15)N was not predictive and minimal
      increases in R(2) values were observed when the delta(15)N value was added to the
      model. CONCLUSIONS: The data do not provide evidence that the dual-isotope method
      is superior for predicting AS/SSB intakes within a southwest Virginian
      population. Our results support the potential of the delta(13)C value of finger
      stick blood to serve as an objective measure of AS/SSB intake. This trial was
      registered at clinicaltrials.gov as NCT02193009.

PMID- 25855121
TI  - Gluten Intake Is Positively Associated with Plasma alpha2-Macroglobulin in Young
      Adults.
AB  - BACKGROUND: Gluten-free foods have increased in popularity over the past decade
      and are now being consumed by individuals without celiac disease. However, the
      physiologic effects of gluten intake in individuals without celiac disease remain
      unknown. High-abundance plasma proteins involved in inflammation, endothelial
      function, and other physiologic pathways may represent potential biomarkers of
      biological effects of gluten intake. OBJECTIVE: The objective was to examine the
      association between gluten intake and plasma proteomic biomarkers in a population
      of adults without clinically diagnosed celiac disease. METHODS: Subjects (n =
      1095) were participants of the Toronto Nutrigenomics and Health Study, a cross
      sectional examination of young adults aged 20-29 y. Dietary gluten intake was
      estimated by using a 1-mo, 196-item semiquantitative food-frequency
      questionnaire. The concentrations of 54 plasma proteins were measured
      simultaneously by liquid chromatography/multiple-reaction monitoring mass
      spectrometry. The association between gluten intake and each proteomic biomarker
      was examined by using general linear models. Analyses were then conducted in
      individuals who do not have the human leukocyte antigen (HLA)-DQ2 or DQ8 risk
      variants required for the development of celiac disease to determine whether any
      associations observed could have been due to undiagnosed cases of celiac disease.
      RESULTS: Increased gluten intake was associated with increased concentrations of
      plasma alpha2-macroglobulin (P = 0.01), a marker of inflammation and cytokine
      release. The association remained after adjusting for age, sex, BMI, ethnicity,
      physical activity, energy intake, fiber intake, and hormonal contraceptive use
      among women. This relation was not modified by HLA risk variants. CONCLUSION:
      Gluten consumption is associated with increased plasma alpha2-macroglobulin in
      young adults, which appears to be independent of celiac disease, suggesting
      possible effects of gluten on inflammation.

PMID- 25855123
TI  - Life course epidemiology: recognising the importance of puberty.

PMID- 25855122
TI  - T-cell Expression of IL10 Is Essential for Tumor Immune Surveillance in the Small
      Intestine.
AB  - IL10 is attributed with immune-suppressive and anti-inflammatory properties,
      which could promote or suppress cancer in the gastrointestinal tract. Loss of
      IL10 exacerbates colonic inflammation, leading to colitis and cancer. Consistent
      with this, transfer of IL10-competent regulatory T cells (Treg) into mice with
      colitis or hereditary polyposis protects against disease, while IL10-deficient
      mice are predisposed to polyposis with increased colon polyp load. Little is
      known about the protective or pathogenic function of IL10 in cancers of the small
      intestine. We found CD4(+) T cells and CD4(+) Foxp3(+) Tregs to be the major
      sources of IL10 in the small intestine and responsible for the increase in IL10
      during polyposis in the APC(Delta468) mouse model of hereditary polyposis.
      Targeted ablation of IL10 in T cells caused severe IL10 deficiency and delayed
      polyp growth. However, these polyps progressively lost cytotoxic activity and
      eventually progressed to cancer. Several observations suggested that the effect
      was due to the loss of IFNgamma-dependent immune surveillance. IL10-incompetent
      CD4(+) T cells failed to secrete IFNgamma when stimulated with polyp antigens and
      were inefficient in T-helper-1 (TH1) commitment. By contrast, the TH17 commitment
      was unaffected. These findings were validated using mice whose T cells
      overexpress IL10. In these mice, we observed high intra-polyp cytotoxic activity
      and attenuation of polyposis. Thus, expression of IL10 by T cells is protective
      and required for immune surveillance in the small intestine.

PMID- 25855124
TI  - Folic acid in pregnancy and mortality from cancer and cardiovascular disease:
      further follow-up of the Aberdeen folic acid supplementation trial.
AB  - BACKGROUND: Supplemental periconceptional folic acid is recommended to reduce the
      risk of fetal neural tube defects. A previous report indicated an elevated risk
      of breast cancer and all cancer deaths in later life among women randomised by
      alternate allocation to high-dose (5 mg/day) folic acid in pregnancy compared
      with placebo; however, findings were based on small numbers of cases. Our aim was
      to extend the previous analysis by including data from an additional 10 years of
      follow-up. METHODS: Records of participants in a large (n=2928) trial of folate
      supplementation (5 or 0.2 mg folic acid, or placebo) in pregnancy in the 1960s
      were linked to central registries in Scotland. Unadjusted and adjusted HRs were
      calculated for all-cause, cardiovascular, all cancer and breast cancer mortality,
      and all cancer and breast cancer morbidity. Analyses were done using (1) data
      from the time of the previous linkage (2002) to March 2013; and (2) data from
      1980 to March 2013. RESULTS: There was no evidence to suggest an excess risk of
      morbidity or mortality in either supplementation group compared with placebo for
      2002-2013 and no associations were seen for the full time period (1980-2013).
      CONCLUSIONS: Findings from this extended follow-up do not support our previous
      observation of an elevated risk of mortality from breast cancer or all cancers in
      later life among women who had taken 5 mg folic acid/day during pregnancy.
      Furthermore, there were no associations with risk of mortality from all-causes,
      all cancers or cardiovascular disease.

PMID- 25855126
TI  - Relationship between female pelvic floor dysfunction and sexual dysfunction: an
      observational study.
AB  - INTRODUCTION: The ability to express one's sexuality and engage in sexual
      activity requires multisystemic coordination involving many psychological
      functions as well as the integrity of the nervous, hormonal, vascular, immune,
      and neuromuscular body structures and functions. AIM: The purpose of this study
      was to investigate the associations among pelvic floor function, sexual function,
      and demographic and clinical characteristics in a population of women initiating
      physical therapy evaluation and treatment for pelvic floor-related dysfunctions
      (urinary incontinence, pelvic organ prolapse, vulvodynia, vaginismus, and
      constipation). METHODS: We consented and collected completed demographic data and
      data related to symptoms and clinical condition on 85 consecutive patients in an
      outpatient physical therapy clinic. Clinical and anthropometric characteristics
      were analyzed descriptively. Analysis of variance and linear regression analyses
      were used to analyze Female Sexual Function Index (FSFI) scale ratings, whereas
      zero-inflated beta-binomial regression was applied to the pain subscale. MAIN
      OUTCOME MEASURES: Main outcome measure was FSFI score, whereas the secondary
      outcome measure was the FSFI subscale score related to pain. RESULTS: Women in
      our sample were 38 years old on average, 33% of whom had given birth and 82% of
      whom had high tone pelvic floor. Being in the middle-tercile age group and
      exhibiting low pelvic floor tone (Beta = 6.8; 95% confidence interval [CI] =
      [1.4; 12.0]) were significantly associated with lower levels of sexual
      dysfunction. Women with low tone pelvic floor also reported lower pain (odds
      ratio = 4.0; 95% CI = [1.6; 9.6]), whereas younger aged and physically
      unsatisfied subjects were more likely not to have sexual activity in the month
      prior to scale measurement. CONCLUSION: In female patients with pelvic floor
      muscle dysfunction undergoing physical therapy and rehabilitation, sexual
      dysfunction appears to be significantly correlated with age and high pelvic floor
      muscle tone.

PMID- 25855125
TI  - Damage-associated molecular pattern-activated neutrophil extracellular trap
      exacerbates sterile inflammatory liver injury.
AB  - Innate immunity plays a crucial role in the response to sterile inflammation such
      as liver ischemia/reperfusion (I/R) injury. The initiation of liver I/R injury
      results in the release of damage-associated molecular patterns, which trigger an
      innate immune and inflammatory cascade through pattern recognition receptors.
      Neutrophils are recruited to the liver after I/R and contribute to organ damage
      and innate immune and inflammatory responses. Formation of neutrophil
      extracellular traps (NETs) has been recently found in response to various
      stimuli. However, the role of NETs during liver I/R injury remains unknown. We
      show that NETs form in the sinusoids of ischemic liver lobes in vivo. This was
      associated with increased NET markers, serum level of myeloperoxidase-DNA
      complexes, and tissue level of citrullinated-histone H3 compared to control mice.
      Treatment with peptidyl-arginine-deiminase 4 inhibitor or DNase I significantly
      protected hepatocytes and reduced inflammation after liver I/R as evidenced by
      inhibition of NET formation, indicating the pathophysiological role of NETs in
      liver I/R injury. In vitro, NETs increase hepatocyte death and induce Kupffer
      cells to release proinflammatory cytokines. Damage-associated molecular patterns,
      such as High Mobility Group Box 1 and histones, released by injured hepatocytes
      stimulate NET formation through Toll-like receptor (TLR4)- and TLR9-MyD88
      signaling pathways. After neutrophil depletion in mice, the adoptive transfer of
      TLR4 knockout or TLR9 knockout neutrophils confers significant protection from
      liver I/R injury with a significant decrease in NET formation. In addition, we
      found inhibition of NET formation by the peptidyl-arginine-deiminase 4 inhibitor
      and that DNase I reduces High Mobility Group Box 1 and histone-mediated liver I/R
      injury. CONCLUSION: Damage-associated molecular patterns released during liver
      I/R promote NET formation through the TLR signaling pathway. Development of NETs
      subsequently exacerbates organ damage and initiates inflammatory responses during
      liver I/R.

PMID- 25855127
TI  - Critical roles of arginine in growth and biofilm development by Streptococcus
      gordonii.
AB  - Streptococcus gordonii is an oral commensal and an early coloniser of dental
      plaque. In vitro, S. gordonii is conditionally auxotrophic for arginine in
      monoculture but biosynthesises arginine when coaggregated with Actinomyces oris.
      Here, we investigated the arginine-responsive regulatory network of S. gordonii
      and the basis for conditional arginine auxotrophy. ArcB, the catabolic ornithine
      carbamoyltransferase involved in arginine degradation, was also essential for
      arginine biosynthesis. However, arcB was poorly expressed following arginine
      depletion, indicating that arcB levels may limit S. gordonii arginine
      biosynthesis. Arginine metabolism gene expression was tightly co-ordinated by
      three ArgR/AhrC family regulators, encoded by argR, ahrC and arcR genes.
      Microarray analysis revealed that > 450 genes were regulated in response to rapid
      shifts in arginine concentration, including many genes involved in adhesion and
      biofilm formation. In a microfluidic salivary biofilm model, low concentrations
      of arginine promoted S. gordonii growth, whereas high concentrations (> 5 mM
      arginine) resulted in dramatic reductions in biofilm biomass and changes to
      biofilm architecture. Collectively, these data indicate that arginine metabolism
      is tightly regulated in S. gordonii and that arginine is critical for gene
      regulation, cellular growth and biofilm formation. Manipulating exogenous
      arginine concentrations may be an attractive approach for oral biofilm control. 

PMID- 25855128
TI  - Nanostructures in superhydrophobic Ti6Al4V hierarchical surfaces control wetting
      state transitions.
AB  - This paper mainly reports the wetting state of liquid droplets on a Ti6Al4V micro
      nanoscale hierarchical structured hydrophobic surface. In this work, the detailed
      action mechanism of the secondary nanostructure in the hierarchical structure on
      the wetting-state transition (from the Wenzel state to the Cassie state) was
      revealed and discussed. The variation of micro-morphology of the sample surface
      was observed using a field emission scanning electron microscope (FE-SEM).
      Furthermore, the apparent contact angle and sliding angle of the droplets on the
      surfaces were measured via a contact angle measurement instrument. The
      theoretical and experimental results indicated that the one-dimensional nanowire
      structure, which was planted on the microstructure surface by the hydrothermal
      method, effectively changed the wetting state of liquid droplets on the surface
      from the Wenzel state to the Cassie state owing to its good size synergies with
      microscale structure. This process not only increased the apparent contact angle
      of liquid droplets on the solid surface (to 161 degrees ), but also decreased the
      sliding angle significantly (to 3 degrees ) and contact angle hysteresis (to ~2
      degrees ), demonstrating the robust non-wetting property. 

PMID- 25855129
TI  - Detection of shiga toxins by lateral flow assay.
AB  - Shiga toxin-producing Escherichia coli (STEC) produce shiga toxins (Stxs) that
      can cause human disease and death. The contamination of food products with STEC
      represents a food safety problem that necessitates rapid and effective detection
      strategies to mitigate risk. In this manuscript, we report the development of a
      colorimetric lateral flow assay (LFA) for the rapid detection of Stxs in <10 min
      using a pair of monoclonal antibodies that bind epitopes common to Stx1 and six
      Stx2 variants. This LFA provides a rapid and sensitive test for the detection of
      Stxs directly from STEC culture supernatants or at risk food samples with a 0.1
      ng/mL limit of detection (LOD) for Stx2a. This Stx LFA is applicable for use in
      the rapid evaluation of Stx production from cultured E. coli strains or as a tool
      to augment current methods as part of food safety testing.

PMID- 25855131
TI  - Perspectives of Behavioral Health Clinicians in a Rural Integrated Primary
      Care/Mental Health Program.
AB  - PURPOSE: This study compares the perspectives of rural and urban mental health
      clinicians working in various Washington State Community Health Centers that have
      implemented an integrated primary care/mental health program. METHODS: We
      conducted a Web-based survey of mental health clinicians (n = 71) who work in an
      integrated primary care/mental health program ("the program") in 1 of 150 safety
      net primary care clinics in Washington State. Most participating clinics are
      Federally Qualified Health Centers or Rural Health Clinics. Pooled survey results
      from clinicians working in rural settings were compared to those working in urban
      settings. Semistructured interviews were conducted with a subset (n = 32) of
      survey respondents. Comments made during these interviews were analyzed for
      themes. FINDINGS: In the survey phase, both rural and urban clinicians generally
      agreed that the program benefitted their patients. Rural respondents were
      particularly appreciative of the flexibility that the program offered when
      planning care. Not surprisingly, social service limitations (such as housing or
      transportation services) were more often mentioned as program limitations. Rural
      clinicians were more likely to note a lack of awareness of program resources
      among other medical providers on the team. CONCLUSIONS: Clinicians working in
      rural primary care clinics value the availability and flexibility of an
      integrated primary care/mental health program as an option for providing mental
      health care for their patients. Clinicians working in rural settings could
      benefit from additional training and program implementation support to best meet
      the needs of their patients.

PMID- 25855130
TI  - Comparative investigation of the efficacy of three different adsorbents against
      OTA-induced toxicity in broiler chickens.
AB  - The aim of our study was to determine the efficacy of three different adsorbents,
      inorganic (modified zeolite), organic (esterified glucomannans) and mixed
      (inorganic and organic components, with the addition of enzymes), in protecting
      broilers from the toxic effects of ochratoxin A in feed. Broilers were fed diets
      containing 2 mg/kg of ochratoxin A (OTA) and supplemented with adsorbents at the
      recommended concentration of 2 g/kg for 21 days. The presence of OTA led to a
      notable reduction in body weight, lower weight gain, increased feed conversion
      and induced histopathological changes in the liver and kidneys. The presence of
      inorganic, organic and mixed adsorbents in contaminated feed only partially
      reduced the negative effects of OTA on the broiler performances. Broilers that
      were fed with adsorbent-supplemented feed reached higher body weight (17.96%,
      19.09% and 13.59%), compared to the group that received only OTA. The presence of
      adsorbents partially alleviated the reduction in feed consumption (22.68%, 12.91%
      and 10.59%), and a similar effect was observed with feed conversion. The applied
      adsorbents have also reduced the intensity of histopathological changes caused by
      OTA; however, they were not able to prevent their onset. After the withdrawal of
      the toxin and adsorbents from the feed (21-42 days), all previously observed
      disturbances in broilers were reduced, but more remarkably in broilers fed with
      adsorbents.

PMID- 25855132
TI  - a-tDCS on the ipsilesional parietal cortex boosts the effects of prism adaptation
      treatment in neglect.
AB  - BACKGROUND AND OBJECTIVE: The aim of the study is to compare the effects of
      multiple sessions of cathodal (c-tDCS) or anodal tDCS (a-tDCS) in modulating the
      beneficial effects of prism adaptation (PA) treatment in neglect patients.
      METHODS: 30 neglect patients were submitted to 10 daily sessions of PA treatment.
      Patients were pseudo-randomly divided into 3 groups. In the c-tDCS-group, each PA
      session was coupled with 20 minutes of cathodal stimulation of the left, intact
      PPC; in the a-tDCS-group, anodal stimulation was applied to PPC of the damaged
      hemisphere; in the Sham group, sham stimulation was applied. Neglect was
      evaluated before and after treatment with the Behavioral Inattention Test.
      RESULTS: Combined tDCS-PA treatment induced stronger neglect improvement in the a
      tDCSgroup as compared to the Sham group. No improvement was found in the c-tDCS
      group, with respect to that normally induced by PA and found in the Sham group.
      CONCLUSIONS: c-tDCS abolished neglect amelioration after PA, possibly because
      stimulation affected the sensorimotor network controlling prism adaptation.
      Instead, a-tDCS PPC boosted neglect amelioration after PA probably thanks to
      increased excitability of residual tissue in the lesioned hemisphere, which in
      turn might reduce dysfunctional over-excitability of the intact hemisphere.

PMID- 25855133
TI  - Gay-Straight Alliances vary on dimensions of youth socializing and advocacy:
      factors accounting for individual and setting-level differences.
AB  - Gay-Straight Alliances (GSAs) are school-based youth settings that could promote
      health. Yet, GSAs have been treated as homogenous without attention to
      variability in how they operate or to how youth are involved in different
      capacities. Using a systems perspective, we considered two primary dimensions
      along which GSAs function to promote health: providing socializing and advocacy
      opportunities. Among 448 students in 48 GSAs who attended six regional
      conferences in Massachusetts (59.8 % LGBQ; 69.9 % White; 70.1 % cisgender
      female), we found substantial variation among GSAs and youth in levels of
      socializing and advocacy. GSAs were more distinct from one another on advocacy
      than socializing. Using multilevel modeling, we identified group and individual
      factors accounting for this variability. In the socializing model, youth and GSAs
      that did more socializing activities did more advocacy. In the advocacy model,
      youth who were more actively engaged in the GSA as well as GSAs whose youth
      collectively perceived greater school hostility and reported greater social
      justice efficacy did more advocacy. Findings suggest potential reasons why GSAs
      vary in how they function in ways ranging from internal provisions of support, to
      visibility raising, to collective social change. The findings are further
      relevant for settings supporting youth from other marginalized backgrounds and
      that include advocacy in their mission.

PMID- 25855134
TI  - Coexistence of pemphigus foliaceus and acquired hemophilia A: A case report.
AB  - Pemphigus foliaceus (PF) is an autoimmune bullous dermatosis with anti-desmoglein
      1 autoantibodies. Acquired hemophilia A (AHA) is a rare coagulation disorder with
      a high mortality rate, caused by anti-factor VIII immunoglobulin G antibodies
      leading to spontaneous severe hemorrhages into skin, muscles or soft tissues.
      This coagulopathy may be associated with malignancies, drug reactions and
      autoimmune disorders including bullous dermatoses. Herein, we demonstrate a first
      report of AHA in the course of pemphigus foliaceus. A 55-year-old woman
      presenting with extensive, erosive, crusted, scaly skin lesions was diagnosed
      with PF based on histopathological and immunofluorescent examination, confirmed
      by the presence of anti-desmoglein-1 antibodies on enzyme-linked immunoassay. She
      developed extensive internal hemorrhages and prolonged external bleeding after
      laparotomy. Based on coagulation tests, AHA was diagnosed. Simultaneous remission
      of pemphigus and coagulopathy occurred with immunosuppressants and recombinant
      activated factor VII. 

PMID- 25855135
TI  - Genetic polymorphisms and expression of HLA-G and its receptors, KIR2DL4 and
      LILRB1, in non-small cell lung cancer.
AB  - Human leukocyte antigen-G (HLA-G) is a nonclassical HLA class I molecule absent
      from most normal tissues but detected in many malignant tumors. It is recognized
      by cells of the immune system using LILRB1, KIR2DL4 and LILRB2 receptors. We
      attempted to find out whether some polymorphisms of HLA-G, LILRB1 and KIR2DL4
      genes are associated with susceptibility to nonsmall cell lung cancer (NSCLC).
      Four polymorphisms in HLA-G, i.e. -964A>G (rs1632947), -725C>G>T (rs1233334), 
      716T>G (rs2249863) in the promoter, and a 14 base pair insertion/deletion (14 bp
      indel) in the 3'-untranslated region (3'UTR), and five in LILRB1 - 5651G>A
      (rs41308748) in intron 14, 5717C>T L622L (rs1061684), 5724G>A E625K (rs16985478),
      5774 C>A P641P (rs41548213) in exon 15, and 5806C>T (rs8101240) in 3'UTR - as
      well as 9620 9A/10A (rs11410751) polymorphism in exon 7 of KIR2DL4 were typed
      using different laboratory techniques. Only one single nucleotide polymorphism
      (SNP) in HLA-G (-964A>G) and one in LILRB1 (5724G>A) were found to influence the
      risk of NSCLC. In addition, 5724G>A was associated with protection from tumor
      cell infiltration of regional lymph nodes. Most importantly, we detected HLA-G
      and LILRB1 expression in tumor specimens, but no correlation with genetic
      polymorphisms was observed. HLA-G and LILRB1 protein expression levels in tumor
      tissue were significantly correlated with tumor stage. 

PMID- 25855137
TI  - Antitumor activity of the MEK inhibitor trametinib on intestinal polyp formation
      in Apc(Delta716) mice involves stromal COX-2.
AB  - Extracellular signal-regulated kinase is an MAPK that is most closely associated
      with cell proliferation, and the MEK/ERK signaling pathway is implicated in
      various human cancers. Although epidermal growth factor receptor, KRAS, and BRAF
      are considered major targets for colon cancer treatment, the precise roles of the
      MEK/ERK pathway, one of their major downstream effectors, during colon cancer
      development remain to be determined. Using Apc(Delta716) mice, a mouse model of
      familial adenomatous polyposis and early-stage sporadic colon cancer formation,
      we show that MEK/ERK signaling is activated not only in adenoma epithelial cells,
      but also in tumor stromal cells including fibroblasts and vascular endothelial
      cells. Eight-week treatment of Apc(Delta716) mice with trametinib, a small
      molecule MEK inhibitor, significantly reduced the number of polyps in the large
      size class, accompanied by reduced angiogenesis and tumor cell proliferation.
      Trametinib treatment reduced the COX-2 level in Apc(Delta716) tumors in vivo and
      in primary culture of intestinal fibroblasts in vitro. Antibody array analysis
      revealed that trametinib and the COX-2 inhibitor rofecoxib both reduced the level
      of CCL2, a chemokine known to be essential for the growth of Apc mutant polyps,
      in intestinal fibroblasts in vitro. Consistently, trametinib treatment reduced
      the Ccl2 mRNA level in Apc(Delta716) tumors in vivo. These results suggest that
      MEK/ERK signaling plays key roles in intestinal adenoma formation in
      Apc(Delta716) mice, at least in part, through COX-2 induction in tumor stromal
      cells.

PMID- 25855138
TI  - Dasatinib-induced gastric antral vascular ectasia in a patient with acute
      lymphoblastic leukaemia.

PMID- 25855136
TI  - New basal cell carcinoma susceptibility loci.
AB  - In an ongoing screen for DNA sequence variants that confer risk of cutaneous
      basal cell carcinoma (BCC), we conduct a genome-wide association study (GWAS) of
      24,988,228 SNPs and small indels detected through whole-genome sequencing of
      2,636 Icelanders and imputed into 4,572 BCC patients and 266,358 controls. Here
      we show the discovery of four new BCC susceptibility loci: 2p24 MYCN
      (rs57244888[C], OR=0.76, P=4.7 * 10(-12)), 2q33 CASP8-ALS2CR12 (rs13014235[C],
      OR=1.15, P=1.5 * 10(-9)), 8q21 ZFHX4 (rs28727938[G], OR=0.70, P=3.5 * 10(-12))
      and 10p14 GATA3 (rs73635312[A], OR=0.74, P=2.4 * 10(-16)). Fine mapping reveals
      that two variants correlated with rs73635312[A] occur in conserved binding sites
      for the GATA3 transcription factor. In addition, expression microarrays and RNA
      seq show that rs13014235[C] and a related SNP rs700635[C] are associated with
      expression of CASP8 splice variants in which sequences from intron 8 are
      retained. 

PMID- 25855140
TI  - The solution structure of human calcium-bound S100A4 mutated at four cysteine
      loci.

PMID- 25855139
TI  - MAGIC populations in crops: current status and future prospects.
AB  - KEY MESSAGE: MAGIC populations present novel challenges and opportunities in
      crops due to their complex pedigree structure. They offer great potential both
      for dissecting genomic structure and for improving breeding populations. The past
      decade has seen the rise of multiparental populations as a study design offering
      great advantages for genetic studies in plants. The genetic diversity of multiple
      parents, recombined over several generations, generates a genetic resource
      population with large phenotypic diversity suitable for high-resolution trait
      mapping. While there are many variations on the general design, this review
      focuses on populations where the parents have all been inter-mated, typically
      termed Multi-parent Advanced Generation Intercrosses (MAGIC). Such populations
      have already been created in model animals and plants, and are emerging in many
      crop species. However, there has been little consideration of the full range of
      factors which create novel challenges for design and analysis in these
      populations. We will present brief descriptions of large MAGIC crop studies
      currently in progress to motivate discussion of population construction,
      efficient experimental design, and genetic analysis in these populations. In
      addition, we will highlight some recent achievements and discuss the
      opportunities and advantages to exploit the unique structure of these resources
      post-QTL analysis for gene discovery.

PMID- 25855141
TI  - Biodiversity of marine scuticociliates (Protozoa, Ciliophora) from China:
      Description of seven morphotypes including a new species, Philaster sinensis
      spec. nov.
AB  - Seven marine scuticociliates, Philaster sinensis spec. nov., Pseudocohnilembus
      hargisi Evans and Thompson, 1964. J. Protozool. 11, 344, Parauronema virginianum
      Thompson, 1967. J. Protozool. 14, 731, Uronemella filificum (Kahl, 1931.
      Tierwelt. Dtl. 21, 181) Song and Wilbert, 2002. Zool. Anz. 241, 317, Cohnilembus
      verminus Kahl, 1931, Parauronema longum Song, 1995. J. Ocean Univ. China. 25, 461
      and Glauconema trihymene Thompson, 1966. J. Protozool. 13, 393, collected from
      Chinese coastal waters, were investigated using live observations, silver
      impregnation methods, and, in the case of the new species, SSU rDNA sequencing.
      Philaster sinensis spec. nov. can be recognized by the combination of the
      following characters: body cylindrical, approximately 130-150 * 35-55 MUm in
      vivo; apical end slightly to distinctly pointed, posterior generally rounded; 19
      22 somatic kineties; M1 triangular, consisting of 13 or 14 transverse rows of
      kinetosomes; M2 comprising 10-12 longitudinal rows; CVP positioned at end of SK1;
      marine habitat. We also provide improved diagnoses for Pseudocohnilembus hargisi,
      Parauronema virginianum, Uronemella filificum and Parauronema longum based on
      their original descriptions as well as the present work. Phylogenetic analyses
      support the monophyly of the genus Philaster.

PMID- 25855142
TI  - Molecular and morphological diversity of the genus Hypotrichomonas (Parabasalia:
      Hypotrichomonadida), with descriptions of six new species.
AB  - The genus HypotrichomonasLee, 1960 belongs to the small parabasalian class
      Hypotrichomonadea. Although five Hypotrichomonas species have been described from
      intestines of lizards and birds, some descriptions were brief and incomplete.
      Only the type species H. acosta has been observed repeatedly. We have established
      23 strains of the genus Hypotrichomonas in culture. Phylogenetic and
      morphological analyses showed that these isolates represent eight distinct
      species, six of which are novel. Three of the species showed unusual morphology,
      such as a reduced undulating membrane, absence of the free part of the recurrent
      flagellum or a costa-like fiber. Our strains were isolated from a wide range of
      hosts including cockroaches, frogs, tortoises, lizards, snakes, marsupials, pigs,
      rodents, and primates. The genus Hypotrichomonas thus contains a relatively large
      number of species that differ in morphology, phylogenetic position and host
      range. It is remarkable that such diversity of hypotrichomonads was previously
      undetected, although a number of studies dealt with intestinal trichomonads of
      vertebrates and invertebrates. Our results indicate that the diversity of the
      genus Hypotrichomonas as well as of the whole Parabasalia is still only poorly
      understood, and the lineages described so far likely represent only a small
      fraction of the true diversity of parabasalids. 

PMID- 25855143
TI  - Identification of neutral and acidic deoxyribonuclease activities in Tetrahymena
      thermophila life stages.
AB  - Deoxyribonucleases (DNases) play a major role in apoptotic DNA
      fragmentation/degradation, and apoptotic-like DNA degradation is also observed
      during conjugation of the ciliate Tetrahymena thermophila; however, the
      characteristics of neutral and acidic DNases are still undefined in its life
      stages. Here, we report the biochemical characterization of DNase activities
      displayed in three different Tetrahymena life stages in a comparative manner.
      Maximum DNase activity of Tetrahymena was observed under acidic conditions,
      indicating that Tetrahymena has strong DNase II-like activities. Zymography
      revealed that Tetrahymena has at least five distinct DNase activity bands at 28,
      32, 33.8, 35.5, and 69-kDa, and that the activities at 32 and 33.8-kDa were also
      secreted into starvation buffer. Cofactor analysis demonstrated that Mg(2+)
      exerted inhibitory effects on neutral DNase activities. Unexpectedly, Mg(2+) and
      Ca(2+) had favorable effects on acidic DNase activities. The DNase activity
      profile of conjugating Tetrahymena cells revealed that the 32 and 33.8-kDa
      activities at pH 5.0 increased from 14 to 18 h of conjugation, corresponding to
      the final resorption of the old macronucleus by lysosomal enzymes during
      programmed nuclear death (PND). Overall, we found that Tetrahymena DNases exhibit
      different biochemical properties and a possible involvement of DNase II-like
      activities in PND.

PMID- 25855144
TI  - Morphology of three new colonial sessile peritrich ciliates, Pseudepistylis
      paramphora n. sp., Zoothamnium paranii n. sp. and Z. hartwigi n. sp., with notes
      on Epicarchesium variabile (Ciliophora, Peritrichia).
AB  - Four colonial sessile peritrichs were discovered during a survey of ciliate
      diversity of coastal waters of the Yellow Sea, Shandong Province, China.
      Following studies of their living morphology, infraciliature and silverline
      system, three were identified as new members of the genera Pseudepistylis and
      Zoothamnium. Pseudepistylis paramphora n. sp. is the second species assigned to
      the genus, which is characterized by its rigid, dichotomously branched stalk,
      reticulate silverline system and marine habitat. Zoothamnium paranii n. sp. was
      isolated from brackish water and Z. hartwigi n. sp. was collected from marine
      water. Zoothamnium paranii is characterized largely by its highly variable zooid
      size and having an extremely long infundibular polykinety 3. Zoothamnium hartwigi
      is separated from its congeners by having two types both of peristomial lip and
      infundibular polykinety 3. We also supply supplementary morphometric data and
      photomicrographs of Epicarchesium variabile based on examinations of specimens in
      vivo and after silver staining. 

PMID- 25855146
TI  - Efficient size control of copper nanoparticles generated in irradiated aqueous
      solutions of star-shaped polyelectrolyte containers.
AB  - The formation of copper nanoparticles (Cu-NPs) in irradiated aqueous solutions of
      star-shaped poly(acrylic acid) (PAA) were studied at two pH values. Transmission
      electron microscopy (TEM) demonstrates that the star-shaped macromolecules loaded
      with Cu(2+) ions can act as individual nanosized containers providing a perfect
      control over the size and size distribution of Cu-NPs. Electron paramagnetic
      resonance (EPR) and optical spectroscopy show a transformation of mechanisms
      controlling the reduction of Cu(2+) ions and the further formation of Cu-NPs. At
      pH 2.9, Cu-NPs are formed from the aquacomplexes of Cu(2+) ions through
      homogeneous nucleation. At pH 4.3, the formation of Cu-NPs occurs inside
      macromolecular containers loaded with Cu(2+) ions, which are bound to carboxylic
      groups of the polyelectrolyte. In the latter case, Cu-NPs apparently ripen from
      preformed hydrated Cu2O seeds, which are thought to result from the ultrasmall
      (Cu(2+))m(OH(-))k(COO(-))n species, thus implying a heterogeneous nucleation. 

PMID- 25855145
TI  - The p53/miR-17/Smurf1 pathway mediates skeletal deformities in an age-related
      model via inhibiting the function of mesenchymal stem cells.
AB  - Osteoporosis is an age-related progressive bone disease. Trp53 (p53) is not only
      a famous senescence marker but also a transcription regulator which played a
      critical role in osteogenesis. However, how p53 contributes to the bone mass loss
      in age-related osteoporosis is still unclear. Here, we found that bone mass and
      osteogenic differentiation capacity of mesenchymal stem cells (MSCs) is
      significantly reduced with advancing age. Serum levels of TNF-alpha and INF-gamma
      and senescence-associated beta-galactosidase, p16, p21 and p53 are significantly
      increased in elder mice, but antipodally, osteogenic marker expression of Runx2,
      ALP and osterix are reduced. Overexpression p53 by lentivirus inhibits
      osteogenesis in young MSCs in culture and upon implantation in NOD/SCID mice
      through inhibiting the transcription of miR-17-92 cluster, which is decreased in
      old mice. In addition, miR-17 mimics could partially rescue the osteogenesis of
      old MSCs both in vitro an in vivo. More importantly, Smurf1 as a direct target
      gene of miR-17, plays an important role in the p53/miR-17 cascade acting on
      osteogenesis. Our findings reveal that p53 inhibits osteogenesis via affecting
      the function of MSCs through miRNA signaling pathways and provide a new potential
      target for treatment in future. 

PMID- 25855147
TI  - The Updated Bottom Up Solution applied to mass spectrometry of soybean oil in a
      dietary supplement gelcap.
AB  - Among the goals of lipidomics applied to triacylglycerols (TAGs) is
      identification of molecular species, degree and location of unsaturation, and
      positions of fatty acyl chains (i.e., identification of regioisomers). Toward
      those ends, we define one, two, and three "Critical Ratios" for Types I, II, and
      III TAGs that provided different aspects of the desired information. Critical
      Ratio 1, [MH](+)/Sigma[DAG](+), is correlated to the degree of unsaturation
      ([MH](+) is the protonated molecule and Sigma[DAG](+) is the sum of
      diacylglycerol-like ions, [DAG](+)); Critical Ratio 2, [AA](+)/[AB](+) for Type
      II TAGs ("ABA/AAB/BAA") and [AC](+)/([AB](+)+[BC](+)) for Type III TAGs
      ("ABC/CBA/BAC/CAB/ACB/BCA"), is correlated to identification of regioisomers; and
      Critical Ratio 3, [BC](+)/[AB](+), provides information about those [DAG](+) from
      Type III TAGs. Furthermore, Critical Ratios are used in the Updated Bottom Up
      Solution (UBUS) to reproduce the mass spectra of TAGs by atmospheric pressure
      chemical ionization mass spectrometry applied to analysis of soybean oil in a
      dietary supplement gelcap. We present a new model for the [MH](+)/Sigma[DAG](+)
      ratio, quantify regioisomers using the [AA](+)/[AB](+) ratio, and describe trends
      for [BC](+)/[AB](+) that have never been reported before. The UBUS is also
      applied to other classes of molecules, i.e., vitamin D and DAGs. The amount of
      vitamin D3 in the gelcap fell from 2011 +/- 22 when received to 1689 +/- 33 just
      prior to expiration. The Critical Ratios constitute a compact data set that can
      provide structural information and also act as a library of mass spectra.

PMID- 25855148
TI  - Applications of microfluidics and microchip electrophoresis for potential
      clinical biomarker analysis.
AB  - This article reviews advances over the last five years in microfluidics and
      microchip-electrophoresis techniques for detection of clinical biomarkers. The
      variety of advantages of miniaturization compared with conventional benchtop
      methods for detecting biomarkers has resulted in increased interest in developing
      cheap, fast, and sensitive techniques. We discuss the development of applications
      of microfluidics and microchip electrophoresis for analysis of different clinical
      samples for pathogen identification, personalized medicine, and biomarker
      detection. We emphasize the advantages of microfluidic techniques over
      conventional methods, which make them attractive future diagnostic tools. We also
      discuss the versatility and adaptability of this technology for analysis of a
      variety of biomarkers, including lipids, small molecules, carbohydrates, nucleic
      acids, proteins, and cells. Finally, we conclude with a discussion of aspects
      that need to be improved to move this technology towards routine clinical and
      point-of-care applications. 

PMID- 25855149
TI  - Magnetic-nanobead-based competitive enzyme-linked aptamer assay for the analysis
      of oxytetracycline in food.
AB  - This study presents a novel analytical method for the detection of
      oxytetracycline (OTC) in complex food matrices based on a direct competitive
      enzyme-linked aptamer assay and magnetic separation technology. In this protocol,
      free OTC competed with horseradish peroxidase labeled OTC (OTC-HRP) for binding
      to the OTC aptamer immobilized on magnetic beads. The parameters that can affect
      the response, such as avidin concentration, aptamer concentration, OTC-HRP
      concentration, incubation temperature, incubation time, blocking agent, and
      binding buffer, were optimized. Under the optimal conditions, the linear range
      for the OTC concentration detection is 0.5-100 ng mL(-1), with a concentration of
      OTC needed to obtain 50 % of the maximum signal of 14.47 ng mL(-1). The limit of
      detection and the limit of quantitation were 0.88 and 3.40 ng mL(-1),
      respectively. There was no obvious cross-reactivity with most of the tetracycline
      pesticides. The recovery rates ranged from 71.0 to 91.2 % for the food samples,
      including chicken, milk, and honey, and the relative standard deviation was less
      than 15.0 %. The proposed method was applied to measure OTC in real samples, and
      was validated using high-performance liquid chromatography. This method has the
      advantages of magnetic separation and the concentration effect of magnetic
      nanoparticles, the specificity of the aptamer, and the high-throughput of
      microtiter plates; it offers a promising approach for the screening of OTC
      because it is simple, rapid, highly sensitive, and has low cost.

PMID- 25855150
TI  - Optimizing the lipidomics workflow for clinical studies--practical
      considerations.
AB  - Lipidomics is increasingly being used in clinical research, offering new
      opportunities for disease prediction and detection. One of the key challenges of
      clinical applications of lipidomics is the high sensitivity of measured lipid
      levels to many analytical, physiological, and environmental factors, which
      therefore must be taken into account when designing the studies. Here we
      critically discuss the complete clinical lipidomics workflow, including selection
      of the subjects, the sample type, the sample preprocessing conditions, and the
      analytical method and methods for data processing. We also review the lipidomics
      applications which investigate the confounding factors such as age, gender,
      fasting time, and handling procedures for measuring blood lipid metabolites. 

PMID- 25855151
TI  - Evaluation of sample preparation and chromatographic separation for the parallel
      determination of taurine and edaravone in rat tissues using HILIC-MS/MS.
AB  - The quantitative analysis of taurine and edaravone in biological sample is
      critical in pharmaceutical studies. Although each of them can be individually
      analyzed by different approaches, concurrent quantification is still a highly
      challenging task with respect to their great polarity variation and the complex
      composition of tissue sample. In the present study, to simultaneously determine
      taurine and edaravone in rat tissue, the sample preparation and chromatographic
      separation conditions were evaluated and discussed in detail. As for the sample
      preparation, four kinds of solvent and the volume ratio of the optimal solvent to
      biological sample were both tested and evaluated based on the chromatographic
      profile, extraction recovery, and matrix effect (ME). The chromatographic
      separation was performed in a reverse phase (RP) and two hydrophilic interaction
      liquid chromatography (HILIC) modes, and the corresponding separation
      efficiencies were assessed using chromatographic parameters like half-width (W
      1/2 ), tailing factor (f t), theoretical plates number (N), and ME. Furthermore,
      adopted composition of two mobile phase systems and the concentrations of the
      additives in the optimum buffer system were also investigated on an Atlantis
      HILIC silica column according to the resultant chromatographic profiles and peak
      areas of the analytes. The optimal results were obtained when the biological
      samples were deproteined by 4-fold volume of methanol/acetonitrile (1:3, v/v) and
      separated on a HILIC column with a gradient elution of acetonitrile/water
      containing 0.2 % formic acid and 10 mM ammonium formate. The proposed approach
      was validated and successfully applied to the parallel determination of the
      tissue distribution of edaravone and taurine in rat tissues.

PMID- 25855152
TI  - Single gold nanorods as optical probes for spectral imaging.
AB  - In this paper, we explain in detail the wavelength dependence of the elastic
      scattering pattern of individual, optically isolated gold nanorods by using
      confocal microscopy in combination with higher order laser modes, i.e.,
      radially/azimuthally polarized laser modes. We demonstrate that the spectral
      dependence of the scattering pattern is mostly caused by the relative strength of
      the gold nanorods' plasmonic modes at different wavelengths. Since the gold
      nanorods' plasmonic modes are determined by the particles' geometrical parameter,
      e.g., size and aspect ratio, as well as the refractive index of the surrounding
      medium, we show that the spectral dependence of the scattering pattern is a
      simple, not invasive way to determine, e.g., the gold nanorod aspect ratio or
      physical variation of the local environment. Thus, a further development of
      spectral imaging of gold nanorods can lead to the employment of this technique in
      biomedical assays involving also living samples. 

PMID- 25855153
TI  - Multianalyte method for the determination of pharmaceuticals in wastewater
      samples using solid-phase extraction and liquid chromatography-tandem mass
      spectrometry.
AB  - A fast and sensitive multianalyte/multiclass high-performance reversed-phase
      liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed
      and validated for the simultaneous analysis of 89 pharmaceuticals in influent and
      effluent wastewater samples. The method developed consists of solid-phase
      extraction (SPE) using a hydrophilic-lipophilic-balanced polymer followed by LC
      MS/MS with electrospray ionization in both positive mode and negative mode. The
      selected pharmaceuticals belong to different classes--analgesic/anti-inflammatory
      drugs, antibiotics, antiepileptics, beta-adrenoceptor-blocking drugs, lipid
      regulating agents, statins, and many others. The influence of the mobile phase
      composition on the sensitivity of the method, and the optimum conditions for SPE
      in terms of analyte recovery were extensively studied. Chromatographic separation
      was performed on an Atlantis T3 (100 mm * 2.1 mm, 3-MUm) column with a gradient
      elution using methanol-0.01% v/v formic acid as the mobile phase in positive
      ionization mode determination and methanol-acetonitrile-1 mM ammonium formate as
      the mobile phase in negative ionization mode determination. Recoveries for most
      of the compounds ranged from 50 to 120%. Precision, expressed as relative
      standard deviations, was always below 15%, and the method detection limits ranged
      from 1.06 ng/L (4-hydroxyomeprazole) to 211 ng/L (metformin). Finally, the method
      developed was applied to the determination of target analytes in wastewater
      samples obtained from the Psyttalia wastewater treatment plant, Athens, Greece.
      Although SPE of pharmaceuticals from wastewater samples and their determination
      by LC-MS/MS is a well-established technique, the uniqueness of this study lies in
      the simultaneous determination of a remarkable number of compounds belonging to
      more than 20 drug classes. Moreover, the LC-MS/MS method has been thoroughly
      optimized so that maximum sensitivity is achieved for most of the compounds,
      making the proposed method a valuable tool for pharmaceutical analysis in
      influent and effluent wastewater at the sub-nanogram per liter level.

PMID- 25855154
TI  - Ten-years, single-center experience with arterial duct stenting in duct-dependent
      pulmonary circulation: early results, learning-curve changes, and mid-term
      outcome.
AB  - OBJECTIVES: To evaluate early results, learning-curve changes, and mid-term
      outcome of arterial duct (AD) stenting in congenital heart disease with duct
      dependent pulmonary circulation (CHD-DPC) in a high-volume, tertiary referral
      center. BACKGROUND: In spite of wide acceptance as cost-effective alternative to
      surgical palliation, AD stenting indications, results and mid-term outcome still
      largely depend on small series, experiences in particular subsets of patients or
      multicenter series with different approaches and interventional philosophy.
      METHODS: Between April 2003 and December 2013, 119 patients underwent AD stenting
      as lower-risk palliation of CHD-DPC at our Institution. Procedural and mid-term
      follow-up data of these patients are reported. RESULTS: The procedure was
      successfully completed in 93.3% of cases, with a complication rate and in
      hospital mortality of 17.6% and 3.6%, respectively. No patient underwent rescue
      surgical shunt but elective Blalock-Taussig shunt was needed in 15 patients
      (13.5%). Over time, favorable trends toward higher feasibility and efficacy in
      complex ductal anatomy as well as lower procedural risk were recorded.
      Presurgical cardiac catheterization (n = 36) showed significant and balanced
      pulmonary artery (PA) growth (Nakata Index +113 +/- 101%; left PA z-score +87 +/-
      52%; right PA z-score +97 +/- 53%, P < 0.001 for all comparisons), without
      significant changes of left-to-right PA diameter ratio. PA growth was
      significantly better in patients with severely hypoplastic PAs at the time of
      duct stabilization (Nakata Index increase 194 +/- 115 vs. 75 +/- 61%, P < 0.001).
      CONCLUSIONS: AD stenting is feasible and effective at low-risk in a high
      percentage of patients with CHD-DPC, promoting significant and balanced PA growth
      mainly in patients with hypoplastic main PAs at duct stabilization.

PMID- 25855155
TI  - Effect of ceralifimod (ONO-4641) on lymphocytes and cardiac function: Randomized,
      double-blind, placebo-controlled trial with an open-label fingolimod arm.
AB  - This randomized, double-blind, placebo-controlled, 6-arm, parallel-design study
      investigated cardiac and hematological pharmacodynamic effects of ceralifimod
      (ONO-4641), a selective sphingosine-1-phosphate (S1P) receptor modulator, over a
      broad dose range in direct comparison with the nonselective S1P modulator
      fingolimod. Healthy subjects were assigned to ceralifimod (0.01, 0.025, 0.05, or
      0.10 mg), fingolimod (0.5 mg), or placebo once daily for 14 days (n = 24 per
      group). After 14 days of treatment, mean absolute lymphocyte count percentage
      change from baseline was greatest in the fingolimod (-62%) and ceralifimod 0.10
      mg (-56%) groups. On treatment cessation, lymphocyte recovery was faster in the
      ceralifimod versus the fingolimod group. Ceralifimod showed dose- and
      concentration-dependent chronotropic effect. Cardiac effects in the fingolimod
      group were dependent on fingolimod-P concentrations. Maximum mean heart rate (HR)
      effect on day 1 was larger with fingolimod (placebo-adjusted change from time
      matched baseline HR [DeltaDeltaHR], -14.9 beats per minute [bpm]) versus
      ceralifimod (DeltaDeltaHR, -6.2 and -12.0 bpm for the 0.05- and 0.10-mg doses,
      respectively). Ceralifimod's effect on the PR interval was minor. Safety
      biomarker results suggest that potential therapeutic doses of ceralifimod, in
      particular the 0.05-mg dose, might result in reduced occurrence of bradycardia,
      atrioventricular block absolute lymphocyte count and grade 3/4 lymphopenia
      compared with fingolimod 0.5 mg. 

PMID- 25855158
TI  - Exploring Ghanaian adolescents' meaning of health and wellbeing: a psychosocial
      perspective.
AB  - There is presently no internationally agreed upon set of indicators for assessing
      adolescent health and what "health and wellbeing" means to adolescents. The
      psychosocial context of family, friends, and school plays a crucial role in the
      construction of health and wellbeing by adolescents. In spite of this, not much
      is known about the meaning Ghanaian adolescents attach to their health and
      wellbeing and the role of stress and social support in the construction of this
      meaning. This study explores how perceived social support and stress influence
      the construction of the meaning of health and wellbeing to Ghanaian adolescents.
      Eleven respondents purposively selected from 770 males and females participated
      in semi-structured interviews, which were transcribed verbatim and analysed with
      thematic analysis. Findings pointed to the fact that health and wellbeing was
      largely construed as "ability to perform daily functions," such as ability to
      take critical decisions and a general sense of vitality and mental strength.
      These were influenced by perceived social support ("encouragement and advice" and
      "religiosity or spirituality") and stress ("teasing, strictness, quarrels, and
      arguments"). These findings suggest that effective communication, mutual respect,
      and support from significant others, in the midst of stressful life events,
      contribute substantially to a holistic construction and meaning of health and
      wellbeing by Ghanaian adolescents. 

PMID- 25855157
TI  - Cell Autonomous and Non-Autonomous Effects of Senescent Cells in the Skin.
AB  - Human and mouse skin accumulate senescent cells in both the epidermis and dermis
      during aging. When chronically present, senescent cells are thought to enhance
      the age-dependent deterioration of the skin during extrinsic and intrinsic aging.
      However, when transiently present, senescent cells promote optimal wound healing.
      Here, we review recent studies on how senescent cells and the senescence
      associated secretory phenotype contribute to different physiological and
      pathophysiological conditions in the skin with a focus on some of the cell
      autonomous and non-autonomous functions of senescent cells in the context of skin
      aging and wound healing. 

PMID- 25855159
TI  - Prevalence of uremic itching in patients undergoing hemodialysis.
AB  - Uremic itching is a common problem with multifactorial etiology seen in
      hemodialysis patients. This study was carried out to determine the factors
      affecting and incidence of itching in patients undergoing hemodialysis treatment.
      The descriptive study was carried out in 130 patients who underwent hemodialysis
      treatment because of end-stage renal disease in Eastern Turkey between October
      2014 and December 2014. A questionnaire prepared by the researcher based on the
      literature and the Visual Analog Scale were used for data collection. The data
      were collected by the researcher through face-to-face interviews in the
      hemodialysis unit. The evaluation of data obtained in the research has been
      performed using SPSS 16.0 software using percentages, chi-square analysis, and t
      test. As a result of the study, 85.4% of the patients were found to have itching,
      the severity of itching was 4.86 +/- 3.01 according to Visual Analog Scale, and
      itching of the patients was found to be affected by serum phosphorus and
      parathyroid hormone levels. Uremic itching continues to be seen as a problem in
      hemodialysis patients. 

PMID- 25855160
TI  - Acoustic Structure Quantification Analysis of the Thyroid in Patients with
      Diffuse Autoimmune Thyroid Disease.
AB  - The aim of this study was to assess whether acoustic structure quantification
      (ASQ) can differentiate normal from pathological thyroid parenchyma in patients
      with diffuse autoimmune thyroid disease (AITD). We evaluated 83 subjects (72
      [87%] women and 11 [13%] men) aged 19 to 94 years with a mean age of 53 years. We
      performed a prospective study (from March 2011 to November 2014) that included 43
      (52%) patients with chronic autoimmune thyroiditis (CAT), 22 (26%) patients with
      Graves' disease (GD), and 18 (22%) healthy volunteers. The ASQ values were
      significantly lower in normal subjects than in subjects with CAT and GD (p <
      0.001). In contrast, the differences between the GD and the CAT patients (p =
      0.23) were not statistically significant. The optimal cutoff ASQ value for which
      the sum of sensitivity and specificity was the highest for the prediction of
      diffuse thyroid pathology was 103 (95% confidence interval = [0.79, 0.95]). At
      this cutoff value, the sensitivity was 83% and the specificity was 89%. Our
      findings suggest that ASQ is a useful method for the assessment of the thyroid in
      patients with AITD. 

PMID- 25855161
TI  - Lymphovascular invasion: assessment and prognostic impact in melanoma and breast
      cancer.
AB  - The presence of lymphovascular invasion is a recognised poor prognostic factor in
      a wide range of tumour types. Vascular invasion was historically identified
      through haematoxylin and eosin staining, however this technique is non-specific
      and differentiates poorly between blood and lymphatic vessels. Newer techniques
      using immunohistochemistry allow more sensitive and specific identification of
      lymphovascular invasion and are able to accurately differentiate between
      lymphatic and blood vessels. This review will discuss the current methods
      available for the assessment of lymphovascular invasion. Additionally, it will
      focus on the role of lymphovascular invasion in breast cancer and melanoma,
      discussing the relative importance of lymphatic and blood vessel invasion in each
      tumour type. 

PMID- 25855162
TI  - Optogenetic evidence for inhibitory signaling from orexin to MCH neurons via
      local microcircuits.
AB  - The lateral hypothalamus (LH) is a key regulator of multiple vital behaviors. The
      firing of brain-wide-projecting LH neurons releases neuropeptides promoting
      wakefulness (orexin/hypocretin; OH), or sleep (melanin-concentrating hormone;
      MCH). OH neurons, which coexpress glutamate and dynorphin, have been proposed to
      excite their neighbors, including MCH neurons, suggesting that LH may sometimes
      coengage its antagonistic outputs. However, it remains unclear if, when, and how
      OH actions promote temporal separation of the sleep and wake signals, a process
      that fails in narcolepsy caused by OH loss. To explore this directly, we paired
      optogenetic stimulation of OH cells (at rates that promoted awakening in vivo)
      with electrical monitoring of MCH cells in mouse brain slices. Membrane potential
      recordings showed that OH cell firing inhibited action potential firing in most
      MCH neurons, an effect that required GABAA but not dynorphin receptors. Membrane
      current analysis showed that OH cell firing increased the frequency of fast
      GABAergic currents in MCH cells, an effect blocked by antagonists of OH but not
      dynorphin or glutamate receptors, and mimicked by bath-applied OH peptide. In
      turn, neural network imaging with a calcium indicator genetically targeted to MCH
      neurons showed that excitation by bath-applied OH peptides occurs in a minority
      of MCH cells. Collectively, our data provide functional microcircuit evidence
      that intra-LH feedforward loops may facilitate appropriate switching between
      sleep and wake signals, potentially preventing sleep disorders. 

PMID- 25855163
TI  - A distinct class of slow (~0.2-2 Hz) intrinsically bursting layer 5 pyramidal
      neurons determines UP/DOWN state dynamics in the neocortex.
AB  - During sleep and anesthesia, neocortical neurons exhibit rhythmic UP/DOWN
      membrane potential states. Although UP states are maintained by synaptic
      activity, the mechanisms that underlie the initiation and robust rhythmicity of
      UP states are unknown. Using a physiologically validated model of UP/DOWN state
      generation in mouse neocortical slices whereby the cholinergic tone present in
      vivo is reinstated, we show that the regular initiation of UP states is driven by
      an electrophysiologically distinct subset of morphologically identified layer 5
      neurons, which exhibit intrinsic rhythmic low-frequency burst firing at ~0.2-2
      Hz. This low-frequency bursting is resistant to block of glutamatergic and
      GABAergic transmission but is absent when slices are maintained in a low Ca(2+)
      medium (an alternative, widely used model of cortical UP/DOWN states), thus
      explaining the lack of rhythmic UP states and abnormally prolonged DOWN states in
      this condition. We also characterized the activity of various other pyramidal and
      nonpyramidal neurons during UP/DOWN states and found that an
      electrophysiologically distinct subset of layer 5 regular spiking pyramidal
      neurons fires earlier during the onset of network oscillations compared with all
      other types of neurons recorded. This study, therefore, identifies an important
      role for cell-type-specific neuronal activity in driving neocortical UP states.

PMID- 25855165
TI  - The role of the posterior cerebellum in saccadic adaptation: a transcranial
      direct current stimulation study.
AB  - The posterior vermis of the cerebellum is considered to be critically involved in
      saccadic adaptation. However, recent evidence suggests that the adaptive decrease
      (backward adaptation) and the adaptive increase (forward adaptation) of saccade
      amplitude rely on partially separate neural substrates. We investigated whether
      the posterior cerebellum could be differentially involved in backward and forward
      adaptation by using transcranial direct current stimulation (TDCS). To do so,
      participants' saccades were adapted backward or forward while they received
      anodal, cathodal, or sham TDCS. In two extra groups, subjects underwent a
      nonadaptation session while receiving anodal or cathodal TDCS to control for the
      direct effects of TDCS on saccadic execution. Surprisingly, cathodal stimulation
      tended to increase the extent of both forward and backward adaptations, while
      anodal TDCS strongly impaired forward adaptation and, to a smaller extent,
      backward adaptation. Forward adaptation was accompanied by a greater increase in
      velocity with cathodal stimulation, and reduced duration of change for anodal
      stimulation. In contrast, the expected velocity decrease in backward adaptation
      was noticeably weaker with anodal stimulation. Stimulation applied during
      nonadaptation sessions did not affect saccadic gain, velocity, or duration,
      demonstrating that the reported effects are not due to direct effects of the
      stimulation on the generation of eye movements. Our results demonstrate that
      cerebellar excitability is critical for saccadic adaptation. Based on our results
      and the growing evidence from studies of vestibulo-ocular reflex and saccadic
      adaptation, we conclude that the plasticity at the level of the oculomotor vermis
      is more fundamentally important for forward adaptation than for backward
      adaptation. 

PMID- 25855164
TI  - Emergence of rich-club topology and coordinated dynamics in development of
      hippocampal functional networks in vitro.
AB  - Recent studies demonstrated that the anatomical network of the human brain shows
      a "rich-club" organization. This complex topological feature implies that highly
      connected regions, hubs of the large-scale brain network, are more densely
      interconnected with each other than expected by chance. Rich-club nodes were
      traversed by a majority of short paths between peripheral regions, underlining
      their potential importance for efficient global exchange of information between
      functionally specialized areas of the brain. Network hubs have also been
      described at the microscale of brain connectivity (so-called "hub neurons").
      Their role in shaping synchronous dynamics and forming microcircuit wiring during
      development, however, is not yet fully understood. The present study aimed to
      investigate the role of hubs during network development, using multi-electrode
      arrays and functional connectivity analysis during spontaneous multi-unit
      activity (MUA) of dissociated primary mouse hippocampal neurons. Over the first 4
      weeks in vitro, functional connectivity significantly increased in strength,
      density, and size, with mature networks demonstrating a robust modular and small
      world topology. As expected by a "rich-get-richer" growth rule of network
      evolution, MUA graphs were found to form rich-clubs at an early stage in
      development (14 DIV). Later on, rich-club nodes were a consistent topological
      feature of MUA graphs, demonstrating high nodal strength, efficiency, and
      centrality. Rich-club nodes were also found to be crucial for MUA dynamics. They
      often served as broker of spontaneous activity flow, confirming that hub nodes
      and rich-clubs may play an important role in coordinating functional dynamics at
      the microcircuit level. 

PMID- 25855166
TI  - A critical role for the anterior thalamus in directing attention to task-relevant
      stimuli.
AB  - The prefrontal cortex mediates adaption to changing environmental contingencies.
      The anterior thalamic nuclei, which are closely interconnected with the
      prefrontal cortex, are important for rodent spatial memory, but their potential
      role in executive function has received scant attention. The current study
      examined whether the anterior thalamic nuclei are involved in attentional
      processes akin to those of prefrontal regions. Remarkably, the results repeatedly
      revealed attentional properties opposite to those of the prefrontal cortex. Two
      separate cohorts of rats with anterior thalamic lesions were tested on an
      attentional set-shifting paradigm that measures not only the ability of stimuli
      dimensions that reliably predict reinforcement to gain attention
      ("intradimensional shift"), but also their ability to shift attention to another
      stimulus dimension when contingencies change ("extradimensional shift"). In stark
      contrast to the effects of prefrontal damage, anterior thalamic lesions impaired
      intradimensional shifts but facilitated extradimensional shifts. Anterior
      thalamic lesion animals were slower to acquire discriminations based on the
      currently relevant stimulus dimension but acquired discriminations involving
      previously irrelevant stimulus dimensions more rapidly than controls. Subsequent
      tests revealed that the critical determinant of whether anterior thalamic lesions
      facilitate extradimensional shifts is the degree to which the stimulus dimension
      has been established as an unreliable predictor of reinforcement over preceding
      trials. This pattern of performance reveals that the anterior thalamic nuclei are
      vital for attending to those stimuli that are the best predictors of reward. In
      their absence, unreliable predictors of reward usurp attentional control. 

PMID- 25855167
TI  - Oscillatory recruitment of bilateral visual cortex during spatial attention to
      competing rhythmic inputs.
AB  - Selective attention uses temporal regularity of relevant inputs to bias the phase
      of ongoing population-level neuronal oscillations. This phase entrainment
      streamlines processing, allowing attended information to arrive at moments of
      high neural excitability. How entrainment resolves competition between spatially
      segregated inputs during visuospatial tasks is not yet established. Using high
      density electroencephalography in humans, a bilateral entrainment response to the
      rhythm (1.3 or 1.5 Hz) of an attended stimulation stream was observed, concurrent
      with a considerably weaker contralateral entrainment to a competing rhythm. That
      ipsilateral visual areas strongly entrained to the attended stimulus is notable
      because competitive inputs to these regions were being driven at an entirely
      different rhythm. Strong modulations of phase locking and weak modulations of
      single-trial power suggest that entrainment was primarily driven by phase
      alignment of ongoing oscillatory activity. In addition, interhemispheric
      differences in entrained phase were found to be modulated by attended hemifield,
      implying that the bilateral nature of the response reflected a functional flow of
      information between hemispheres. This modulation was strongest at the third of at
      least four harmonics that were strongly entrained. Ipsilateral increases in alpha
      band (8-12 Hz) power were also observed during bilateral entrainment, reflecting
      suppression of the ignored stimulation stream. Furthermore, both entrainment and
      alpha lateralization significantly affected task performance. We conclude that
      oscillatory entrainment is a functionally relevant mechanism that synchronizes
      endogenous activity across the cortical hierarchy to resolve spatial competition.
      We further speculate that concurrent suppression of ignored input might
      facilitate the widespread propagation of attended information during spatial
      attention. 

PMID- 25855168
TI  - Neuronal pentraxin 1 negatively regulates excitatory synapse density and synaptic
      plasticity.
AB  - In mature neurons, the number of synapses is determined by a neuronal activity
      dependent dynamic equilibrium between positive and negative regulatory factors.
      We hypothesized that neuronal pentraxin (NP1), a proapoptotic protein induced by
      low neuronal activity, could be a negative regulator of synapse density because
      it is found in dystrophic neurites in Alzheimer's disease-affected brains. Here,
      we report that knockdown of NP1 increases the number of excitatory synapses and
      neuronal excitability in cultured rat cortical neurons and enhances excitatory
      drive and long-term potentiation in the hippocampus of behaving mice. Moreover,
      we found that NP1 regulates the surface expression of the Kv7.2 subunit of the
      Kv7 family of potassium channels that control neuronal excitability. Furthermore,
      pharmacological activation of Kv7 channels prevents, whereas inhibition mimics,
      the increase in synaptic proteins evoked by the knockdown of NP1. These results
      indicate that NP1 negatively regulates excitatory synapse number by modulating
      neuronal excitability and show that NP1 restricts excitatory synaptic plasticity.

PMID- 25855169
TI  - The increased sensitivity of irregular peripheral canal and otolith vestibular
      afferents optimizes their encoding of natural stimuli.
AB  - Efficient processing of incoming sensory input is essential for an organism's
      survival. A growing body of evidence suggests that sensory systems have developed
      coding strategies that are constrained by the statistics of the natural
      environment. Consequently, it is necessary to first characterize neural responses
      to natural stimuli to uncover the coding strategies used by a given sensory
      system. Here we report for the first time the statistics of vestibular rotational
      and translational stimuli experienced by rhesus monkeys during natural (e.g.,
      walking, grooming) behaviors. We find that these stimuli can reach intensities as
      high as 1500 deg/s and 8 G. Recordings from afferents during naturalistic
      rotational and linear motion further revealed strongly nonlinear responses in the
      form of rectification and saturation, which could not be accurately predicted by
      traditional linear models of vestibular processing. Accordingly, we used linear
      nonlinear cascade models and found that these could accurately predict responses
      to naturalistic stimuli. Finally, we tested whether the statistics of natural
      vestibular signals constrain the neural coding strategies used by peripheral
      afferents. We found that both irregular otolith and semicircular canal afferents,
      because of their higher sensitivities, were more optimized for processing natural
      vestibular stimuli as compared with their regular counterparts. Our results
      therefore provide the first evidence supporting the hypothesis that the neural
      coding strategies used by the vestibular system are matched to the statistics of
      natural stimuli. 

PMID- 25855170
TI  - Single-unit activity during natural vision: diversity, consistency, and spatial
      sensitivity among AF face patch neurons.
AB  - Several visual areas within the STS of the macaque brain respond strongly to
      faces and other biological stimuli. Determining the principles that govern neural
      responses in this region has proven challenging, due in part to the inherently
      complex stimulus domain of dynamic biological stimuli that are not captured by an
      easily parameterized stimulus set. Here we investigated neural responses in one
      fMRI-defined face patch in the anterior fundus (AF) of the STS while macaques
      freely view complex videos rich with natural social content. Longitudinal single
      unit recordings allowed for the accumulation of each neuron's responses to
      repeated video presentations across sessions. We found that individual neurons,
      while diverse in their response patterns, were consistently and deterministically
      driven by the video content. We used principal component analysis to compute a
      family of eigenneurons, which summarized 24% of the shared population activity in
      the first two components. We found that the most prominent component of AF
      activity reflected an interaction between visible body region and scene layout.
      Close-up shots of faces elicited the strongest neural responses, whereas far away
      shots of faces or close-up shots of hindquarters elicited weak or inhibitory
      responses. Sensitivity to the apparent proximity of faces was also observed in
      gamma band local field potential. This category-selective sensitivity to spatial
      scale, together with the known exchange of anatomical projections of this area
      with regions involved in visuospatial analysis, suggests that the AF face patch
      may be specialized in aspects of face perception that pertain to the layout of a
      social scene. 

PMID- 25855171
TI  - Fertility-regulating Kiss1 neurons arise from hypothalamic POMC-expressing
      progenitors.
AB  - Hypothalamic neuronal populations are central regulators of energy homeostasis
      and reproductive function. However, the ontogeny of these critical hypothalamic
      neuronal populations is largely unknown. We developed a novel approach to examine
      the developmental pathways that link specific subtypes of neurons by combining
      embryonic and adult ribosome-tagging strategies in mice. This new method shows
      that Pomc-expressing precursors not only differentiate into discrete neuronal
      populations that mediate energy balance (POMC and AgRP neurons), but also into
      neurons critical for puberty onset and the regulation of reproductive function
      (Kiss1 neurons). These results demonstrate a developmental link between nutrient
      sensing and reproductive neuropeptide synthesizing neuronal populations and
      suggest a potential pathway that could link maternal nutrition to reproductive
      development in the offspring. 

PMID- 25855172
TI  - Long-term memory formation in Drosophila requires training-dependent glial
      transcription.
AB  - Long-term memory (LTM) formation requires de novo gene expression in neurons, and
      subsequent structural and functional modification of synapses. However, the
      importance of gene expression in glia during this process has not been well
      studied. In this report, we characterize a cell adhesion molecule, Klingon (Klg),
      which is required for LTM formation in Drosophila. We found that Klg localizes to
      the juncture between neurons and glia, and expression in both cell types is
      required for LTM. We further found that expression of a glial gene, repo, is
      reduced in klg mutants and knockdown lines. repo expression is required for LTM,
      and expression increases upon LTM induction. In addition, increasing repo
      expression in glia is sufficient to restore LTM in klg knockdown lines. These
      data indicate that neuronal activity enhances Klg-mediated neuron-glia
      interactions, causing an increase in glial expression of repo. Repo is a
      homeodomain transcription factor, suggesting that further downstream glial gene
      expression is also required for LTM. 

PMID- 25855173
TI  - Egr3-dependent muscle spindle stretch receptor intrafusal muscle fiber
      differentiation and fusimotor innervation homeostasis.
AB  - Muscle stretch proprioceptors (muscle spindles) are required for stretch reflexes
      and locomotor control. Proprioception abnormalities are observed in many human
      neuropathies, but the mechanisms involved in establishing and maintaining muscle
      spindle innervation and function are still poorly understood. During skeletal
      muscle development, sensory (Ia-afferent) innervation induces contacted myotubes
      to transform into intrafusal muscle fibers that form the stretch receptor core.
      The transcriptional regulator Egr3 is induced in Ia-afferent contacted myotubes
      by Neuregulin1 (Nrg1)/ErbB receptor signaling and it has an essential role in
      spindle morphogenesis and function. Because Egr3 is widely expressed during
      development and has a pleiotropic function, whether Egr3 functions primarily in
      skeletal muscle, Ia-afferent neurons, or in Schwann cells that myelinate Ia
      afferent axons remains unresolved. In the present studies, cell-specific ablation
      of Egr3 in mice showed that it has a skeletal muscle autonomous function in
      stretch receptor development. Moreover, using genetic tracing, we found that Ia
      afferent contacted Egr3-deficient myotubes were induced in normal numbers, but
      their development was blocked to generate one to two shortened fibers that failed
      to express some characteristic myosin heavy chain (MyHC) proteins. These "spindle
      remnants" persisted into adulthood, remained innervated by Ia-afferents, and
      expressed neurotrophin3 (NT3), which is required for Ia-afferent neuron survival.
      However, they were not innervated by fusimotor axons and they did not express
      glial derived neurotrophic factor (GDNF), which is essential for fusimotor neuron
      survival. These results demonstrate that Egr3 has an essential role in regulating
      gene expression that promotes normal intrafusal muscle fiber differentiation and
      fusimotor innervation homeostasis. 

PMID- 25855174
TI  - Network structure shapes spontaneous functional connectivity dynamics.
AB  - The structural organization of the brain constrains the range of interactions
      between different regions and shapes ongoing information processing. Therefore,
      it is expected that large-scale dynamic functional connectivity (FC) patterns, a
      surrogate measure of coordination between brain regions, will be closely tied to
      the fiber pathways that form the underlying structural network. Here, we
      empirically examined the influence of network structure on FC dynamics by
      comparing resting-state FC (rsFC) obtained using BOLD-fMRI in macaques (Macaca
      fascicularis) to structural connectivity derived from macaque axonal tract
      tracing studies. Consistent with predictions from simulation studies, the
      correspondence between rsFC and structural connectivity increased as the sample
      duration increased. Regions with reciprocal structural connections showed the
      most stable rsFC across time. The data suggest that the transient nature of FC is
      in part dependent on direct underlying structural connections, but also that
      dynamic coordination can occur via polysynaptic pathways. Temporal stability was
      found to be dependent on structural topology, with functional connections within
      the rich-club core exhibiting the greatest stability over time. We discuss these
      findings in light of highly variable functional hubs. The results further
      elucidate how large-scale dynamic functional coordination exists within a fixed
      structural architecture. 

PMID- 25855175
TI  - Imaging auditory representations of song and syllables in populations of
      sensorimotor neurons essential to vocal communication.
AB  - Vocal communication depends on the coordinated activity of sensorimotor neurons
      important to vocal perception and production. How vocalizations are represented
      by spatiotemporal activity patterns in these neuronal populations remains poorly
      understood. Here we combined intracellular recordings and two-photon calcium
      imaging in anesthetized adult zebra finches (Taeniopygia guttata) to examine how
      learned birdsong and its component syllables are represented in identified
      projection neurons (PNs) within HVC, a sensorimotor region important for song
      perception and production. These experiments show that neighboring HVC PNs can
      respond at markedly different times to song playback and that different syllables
      activate spatially intermingled PNs within a local (~100 MUm) region of HVC.
      Moreover, noise correlations were stronger between PNs that responded most
      strongly to the same syllable and were spatially graded within and between
      classes of PNs. These findings support a model in which syllabic and temporal
      features of song are represented by spatially intermingled PNs functionally
      organized into cell- and syllable-type networks within local spatial scales in
      HVC.

PMID- 25855176
TI  - Neuromodulatory effect of Galphas- or Galphaq-coupled G-protein-coupled receptor
      on NMDA receptor selectively activates the NMDA receptor/Ca2+/calcineurin/cAMP
      response element-binding protein-regulated transcriptional coactivator 1 pathway
      to effectively induce brain-derived neurotrophic factor expression in neurons.
AB  - Although coordinated molecular signaling through excitatory and modulatory
      neurotransmissions is critical for the induction of immediate early genes (IEGs),
      which lead to effective changes in synaptic plasticity, the intracellular
      mechanisms responsible remain obscure. Here we measured the expression of IEGs
      and used bioluminescence imaging to visualize the expression of Bdnf when GPCRs,
      major neuromodulator receptors, were stimulated. Stimulation of pituitary
      adenylate cyclase-activating polypeptide (PACAP)-specific receptor (PAC1), a
      Galphas/q-protein-coupled GPCR, with PACAP selectively activated the calcineurin
      (CN) pathway that is controlled by calcium signals evoked via NMDAR. This
      signaling pathway then induced the expression of Bdnf and CN-dependent IEGs
      through the nuclear translocation of CREB-regulated transcriptional coactivator 1
      (CRTC1). Intracerebroventricular injection of PACAP and intraperitoneal
      administration of MK801 in mice demonstrated that functional interactions between
      PAC1 and NMDAR induced the expression of Bdnf in the brain. Coactivation of NMDAR
      and PAC1 synergistically induced the expression of Bdnf attributable to selective
      activation of the CN pathway. This CN pathway-controlled expression of Bdnf was
      also induced by stimulating other Galphas- or Galphaq-coupled GPCRs, such as
      dopamine D1, adrenaline beta, CRF, and neurotensin receptors, either with their
      cognate agonists or by direct stimulation of the protein kinase A (PKA)/PKC
      pathway with chemical activators. Thus, the GPCR-induced expression of IEGs in
      coordination with NMDAR might occur via the selective activation of the
      CN/CRTC1/CREB pathway under simultaneous excitatory and modulatory synaptic
      transmissions in neurons if either the Galphas/adenylate cyclase/PKA or
      Galphaq/PLC/PKC-mediated pathway is activated. 

PMID- 25855177
TI  - Context-induced reinstatement of methamphetamine seeking is associated with
      unique molecular alterations in Fos-expressing dorsolateral striatum neurons.
AB  - Context-induced reinstatement of drug seeking is a well established animal model
      for assessing the neural mechanisms underlying context-induced drug relapse, a
      major factor in human drug addiction. Neural activity in striatum has previously
      been shown to contribute to context-induced reinstatement of heroin, cocaine, and
      alcohol seeking, but not yet for methamphetamine seeking. In this study, we found
      that context-induced reinstatement of methamphetamine seeking increased
      expression of the neural activity marker Fos in dorsal but not ventral striatum.
      Reversible inactivation of neural activity in dorsolateral but not dorsomedial
      striatum using the GABA agonists muscimol and baclofen decreased context-induced
      reinstatement. Based on our previous findings that Fos-expressing neurons play a
      critical role in conditioned drug effects, we assessed whether context-induced
      reinstatement was associated with molecular alterations selectively induced
      within context-activated Fos-expressing neurons. We used fluorescence-activated
      cell sorting to isolate reinstatement-activated Fos-positive neurons from Fos
      negative neurons in dorsal striatum and used quantitative PCR to assess gene
      expression within these two populations of neurons. Context-induced reinstatement
      was associated with increased expression of the immediate early genes Fos and
      FosB and the NMDA receptor subunit gene Grin2a in only Fos-positive neurons.
      RNAscope in situ hybridization confirmed that Grin2a, as well as Grin2b,
      expression were increased in only Fos-positive neurons from dorsolateral, but not
      dorsomedial, striatum. Our results demonstrate an important role of dorsolateral
      striatum in context-induced reinstatement of methamphetamine seeking and that
      this reinstatement is associated with unique gene alterations in Fos-expressing
      neurons. 

PMID- 25855179
TI  - Abstract representations of associated emotions in the human brain.
AB  - Emotions can be aroused by various kinds of stimulus modalities. Recent
      neuroimaging studies indicate that several brain regions represent emotions at an
      abstract level, i.e., independently from the sensory cues from which they are
      perceived (e.g., face, body, or voice stimuli). If emotions are indeed
      represented at such an abstract level, then these abstract representations should
      also be activated by the memory of an emotional event. We tested this hypothesis
      by asking human participants to learn associations between emotional stimuli
      (videos of faces or bodies) and non-emotional stimuli (fractals). After
      successful learning, fMRI signals were recorded during the presentations of
      emotional stimuli and emotion-associated fractals. We tested whether emotions
      could be decoded from fMRI signals evoked by the fractal stimuli using a
      classifier trained on the responses to the emotional stimuli (and vice versa).
      This was implemented as a whole-brain searchlight, multivoxel activation pattern
      analysis, which revealed successful emotion decoding in four brain regions:
      posterior cingulate cortex (PCC), precuneus, MPFC, and angular gyrus. The same
      analysis run only on responses to emotional stimuli revealed clusters in PCC,
      precuneus, and MPFC. Multidimensional scaling analysis of the activation patterns
      revealed clear clustering of responses by emotion across stimulus types. Our
      results suggest that PCC, precuneus, and MPFC contain representations of emotions
      that can be evoked by stimuli that carry emotional information themselves or by
      stimuli that evoke memories of emotional stimuli, while angular gyrus is more
      likely to take part in emotional memory retrieval. 

PMID- 25855178
TI  - DSCAM promotes refinement in the mouse retina through cell death and restriction
      of exploring dendrites.
AB  - In this study we develop and use a gain-of-function mouse allele of the Down
      syndrome cell adhesion molecule (Dscam) to complement loss-of-function models. We
      assay the role of Dscam in promoting cell death, spacing, and laminar targeting
      of neurons in the developing mouse retina. We find that ectopic or overexpression
      of Dscam is sufficient to drive cell death. Gain-of-function studies indicate
      that Dscam is not sufficient to increase spatial organization, prevent cell-to
      cell pairing, or promote active avoidance in the mouse retina, despite the
      similarity of the Dscam loss-of-function phenotype in the mouse retina to
      phenotypes observed in Drosophila Dscam1 mutants. Both gain- and loss-of-function
      studies support a role for Dscam in targeting neurites; DSCAM is necessary for
      precise dendrite lamination, and is sufficient to retarget neurites of outer
      retinal cells after ectopic expression. We further demonstrate that DSCAM guides
      dendrite targeting in type 2 dopaminergic amacrine cells, by restricting the
      stratum in which exploring retinal dendrites stabilize, in a Dscam dosage
      dependent manner. Based on these results we propose a single model to account for
      the numerous Dscam gain- and loss-of-function phenotypes reported in the mouse
      retina whereby DSCAM eliminates inappropriately placed cells and connections. 

PMID- 25855180
TI  - Abnormal excitability and episodic low-frequency oscillations in the cerebral
      cortex of the tottering mouse.
AB  - The Ca(2+) channelopathies caused by mutations of the CACNA1A gene that encodes
      the pore-forming subunit of the human Cav2.1 (P/Q-type) voltage-gated Ca(2+)
      channel include episodic ataxia type 2 (EA2). Although, in EA2 the emphasis has
      been on cerebellar dysfunction, patients also exhibit episodic, nonmotoric
      abnormalities involving the cerebral cortex. This study demonstrates episodic,
      low-frequency oscillations (LFOs) throughout the cerebral cortex of tottering
      (tg/tg) mice, a widely used model of EA2. Ranging between 0.035 and 0.11 Hz, the
      LFOs in tg/tg mice can spontaneously develop very high power, referred to as a
      high-power state. The LFOs in tg/tg mice are mediated in part by neuronal
      activity as tetrodotoxin decreases the oscillations and cortical neuron discharge
      contain the same low frequencies. The high-power state involves compensatory
      mechanisms because acutely decreasing P/Q-type Ca(2+) channel function in either
      wild-type (WT) or tg/tg mice does not induce the high-power state. In contrast,
      blocking l-type Ca(2+) channels, known to be upregulated in tg/tg mice, reduces
      the high-power state. Intriguingly, basal excitatory glutamatergic
      neurotransmission constrains the high-power state because blocking ionotropic or
      metabotropic glutamate receptors results in high-power LFOs in tg/tg but not WT
      mice. The high-power LFOs are decreased markedly by acetazolamide and 4
      aminopyridine, the primary treatments for EA2, suggesting disease relevance.
      Together, these results demonstrate that the high-power LFOs in the tg/tg
      cerebral cortex represent a highly abnormal excitability state that may underlie
      noncerebellar symptoms that characterize CACNA1A mutations. 

PMID- 25855181
TI  - Muscarinic receptors modulate dendrodendritic inhibitory synapses to sculpt
      glomerular output.
AB  - Cholinergic [acetylcholine (ACh)] axons from the basal forebrain innervate
      olfactory bulb glomeruli, the initial site of synaptic integration in the
      olfactory system. Both nicotinic acetylcholine receptors (nAChRs) and muscarinic
      acetylcholine receptors (mAChRs) are expressed in glomeruli. The activation of
      nAChRs directly excites both mitral/tufted cells (MTCs) and external tufted cells
      (ETCs), the two major excitatory neurons that transmit glomerular output. The
      functional roles of mAChRs in glomerular circuits are unknown. We show that the
      restricted glomerular application of ACh causes rapid, brief nAChR-mediated
      excitation of both MTCs and ETCs in the mouse olfactory bulb. This excitation is
      followed by mAChR-mediated inhibition, which is blocked by GABAA receptor
      antagonists, indicating the engagement of periglomerular cells (PGCs) and/or
      short axon cells (SACs), the two major glomerular inhibitory neurons. Indeed,
      selective activation of glomerular mAChRs, with ionotropic GluRs and nAChRs
      blocked, increased IPSCs in MTCs and ETCs, indicating that mAChRs recruit
      glomerular inhibitory circuits. Selective activation of glomerular mAChRs in the
      presence of tetrodotoxin increased IPSCs in all glomerular neurons, indicating
      action potential-independent enhancement of GABA release from PGC and/or SAC
      dendrodendritic synapses. mAChR-mediated enhancement of GABA release also
      presynaptically suppressed the first synapse of the olfactory system via GABAB
      receptors on sensory terminals. Together, these results indicate that cholinergic
      modulation of glomerular circuits is biphasic, involving an initial excitation of
      MTC/ETCs mediated by nAChRs followed by inhibition mediated directly by mAChRs on
      PGCs/SACs. This may phasically enhance the sensitivity of glomerular outputs to
      odorants, an action that is consistent with recent in vivo findings. 

PMID- 25855182
TI  - Axonal amphoterin mRNA is regulated by translational control and enhances axon
      outgrowth.
AB  - High mobility group (HMG) proteins concentrate in the nucleus, interacting with
      chromatin. Amphoterin is an HMG protein (HMGB1) that has been shown to have
      extranuclear functions and can be secreted from some cell types. Exogenous
      amphoterin can increase neurite growth, suggesting that the secreted protein may
      have growth promoting activities in neurons. Consistent with this, we show that
      depletion of amphoterin mRNA from cultured adult rat DRG neurons attenuates
      neurite outgrowth, pointing to autocrine or paracrine mechanisms for its growth
      promoting effects. The mRNA encoding amphoterin localizes to axonal processes and
      we showed recently that its 3'-UTR is sufficient for axonal localization of
      heterologous transcripts (Donnelly et al., 2013). Here, we show that amphoterin
      mRNA is transported constitutively into axons of adult DRG neurons. A
      preconditioning nerve injury increases the levels of amphoterin protein in axons
      without a corresponding increase in amphoterin mRNA in the axons. A 60 nucleotide
      region of the amphoterin mRNA 3'-UTR is necessary and sufficient for its
      localization into axons of cultured sensory neurons. Amphoterin mRNA 3'-UTR is
      also sufficient for axonal localization in distal axons of DRG neurons in vivo.
      Overexpression of axonally targeted amphoterin mRNA increases axon outgrowth in
      cultured sensory neurons, but axon growth is not affected when the overexpressed
      mRNA is restricted to the cell body. 

PMID- 25855183
TI  - Synergistic action of dendritic mitochondria and creatine kinase maintains ATP
      homeostasis and actin dynamics in growing neuronal dendrites.
AB  - The distribution of mitochondria within mature, differentiated neurons is clearly
      adapted to their regional physiological needs and can be perturbed under various
      pathological conditions, but the function of mitochondria in developing neurons
      has been less well studied. We have studied mitochondrial distribution within
      developing mouse cerebellar Purkinje cells and have found that active delivery of
      mitochondria into their dendrites is a prerequisite for proper dendritic
      outgrowth. Even when mitochondria in the Purkinje cell bodies are functioning
      normally, interrupting the transport of mitochondria into their dendrites
      severely disturbs dendritic growth. Additionally, we find that the growth of
      atrophic dendrites lacking mitochondria can be rescued by activating ATP
      phosphocreatine exchange mediated by creatine kinase (CK). Conversely, inhibiting
      cytosolic CKs decreases dendritic ATP levels and also disrupts dendrite
      development. Mechanistically, this energy depletion appears to perturb normal
      actin dynamics and enhance the aggregation of cofilin within growing dendrites,
      reminiscent of what occurs in neurons overexpressing the dephosphorylated form of
      cofilin. These results suggest that local ATP synthesis by dendritic mitochondria
      and ATP-phosphocreatine exchange act synergistically to sustain the cytoskeletal
      dynamics necessary for dendritic development. 

PMID- 25855184
TI  - alpha-Synuclein-independent histopathological and motor deficits in mice lacking
      the endolysosomal Parkinsonism protein Atp13a2.
AB  - Accumulating evidence from genetic and biochemical studies implicates dysfunction
      of the autophagic-lysosomal pathway as a key feature in the pathogenesis of
      Parkinson's disease (PD). Most studies have focused on accumulation of neurotoxic
      alpha-synuclein secondary to defects in autophagy as the cause of
      neurodegeneration, but abnormalities of the autophagic-lysosomal system likely
      mediate toxicity through multiple mechanisms. To further explore how
      endolysosomal dysfunction causes PD-related neurodegeneration, we generated a
      murine model of Kufor-Rakeb syndrome (KRS), characterized by early-onset
      Parkinsonism with additional neurological features. KRS is caused by recessive
      loss-of-function mutations in the ATP13A2 gene encoding the endolysosomal ATPase
      ATP13A2. We show that loss of ATP13A2 causes a specific protein trafficking
      defect, and that Atp13a2 null mice develop age-related motor dysfunction that is
      preceded by neuropathological changes, including gliosis, accumulation of
      ubiquitinated protein aggregates, lipofuscinosis, and endolysosomal
      abnormalities. Contrary to predictions from in vitro data, in vivo mouse genetic
      studies demonstrate that these phenotypes are alpha-synuclein independent. Our
      findings indicate that endolysosomal dysfunction and abnormalities of alpha
      synuclein homeostasis are not synonymous, even in the context of an endolysosomal
      genetic defect linked to Parkinsonism, and highlight the presence of alpha
      synuclein-independent neurotoxicity consequent to endolysosomal dysfunction. 

PMID- 25855185
TI  - The mediodorsal thalamus drives feedforward inhibition in the anterior cingulate
      cortex via parvalbumin interneurons.
AB  - Although the medial prefrontal cortex (mPFC) is classically defined by its
      reciprocal connections with the mediodorsal thalamic nucleus (MD), the nature of
      information transfer between MD and mPFC is poorly understood. In sensory
      thalamocortical pathways, thalamic recruitment of feedforward inhibition mediated
      by fast-spiking, putative parvalbumin-expressing (PV) interneurons is a key
      feature that enables cortical neurons to represent sensory stimuli with high
      temporal fidelity. Whether a similar circuit mechanism is in place for the
      projection from the MD (a higher-order thalamic nucleus that does not receive
      direct input from the periphery) to the mPFC is unknown. Here we show in mice
      that inputs from the MD drive disynaptic feedforward inhibition in the dorsal
      anterior cingulate cortex (dACC) subregion of the mPFC. In particular, we
      demonstrate that axons arising from MD neurons directly synapse onto and excite
      PV interneurons that in turn mediate feedforward inhibition of pyramidal neurons
      in layer 3 of the dACC. This feedforward inhibition in the dACC limits the time
      window during which pyramidal neurons integrate excitatory synaptic inputs and
      fire action potentials, but in a manner that allows for greater flexibility than
      in sensory cortex. These findings provide a foundation for understanding the role
      of MD-PFC circuit function in cognition. 

PMID- 25855186
TI  - Miro's N-terminal GTPase domain is required for transport of mitochondria into
      axons and dendrites.
AB  - Mitochondria are dynamically transported in and out of neuronal processes to
      maintain neuronal excitability and synaptic function. In higher eukaryotes, the
      mitochondrial GTPase Miro binds Milton/TRAK adaptor proteins linking microtubule
      motors to mitochondria. Here we show that Drosophila Miro (dMiro), which has
      previously been shown to be required for kinesin-driven axonal transport, is also
      critically required for the dynein-driven distribution of mitochondria into
      dendrites. In addition, we used the loss-of-function mutations dMiroT25N and
      dMiroT460N to determine the significance of dMiro's N-terminal and C-terminal
      GTPase domains, respectively. Expression of dMiroT25N in the absence of
      endogenous dMiro caused premature lethality and arrested development at a pupal
      stage. dMiroT25N accumulated mitochondria in the soma of larval motor and sensory
      neurons, and prevented their kinesin-dependent and dynein-dependent distribution
      into axons and dendrites, respectively. dMiroT25N mutant mitochondria also were
      severely fragmented and exhibited reduced kinesin and dynein motility in axons.
      In contrast, dMiroT460N did not impair viability, mitochondrial size, or the
      distribution of mitochondria. However, dMiroT460N reduced dynein motility during
      retrograde mitochondrial transport in axons. Finally, we show that substitutions
      analogous to the constitutively active Ras-G12V mutation in dMiro's N-terminal
      and C-terminal GTPase domains cause neomorphic phenotypic effects that are likely
      unrelated to the normal function of each GTPase domain. Overall, our analysis
      indicates that dMiro's N-terminal GTPase domain is critically required for
      viability, mitochondrial size, and the distribution of mitochondria out of the
      neuronal soma regardless of the employed motor, likely by promoting the
      transition from a stationary to a motile state. 

PMID- 25855187
TI  - A structural role for the synaptobrevin 2 transmembrane domain in dense-core
      vesicle fusion pores.
AB  - Ca(2+)-triggered release of neurotransmitters and hormones depends on soluble N
      ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) to drive
      the fusion of the vesicle and plasma membranes. The formation of the SNARE
      complex by the vesicle SNARE synaptobrevin 2 (syb2) and the two plasma membrane
      SNAREs syntaxin (syx) and SNAP-25 draws the two membranes together, but the
      events that follow membrane juxtaposition, and the ways that SNAREs remodel lipid
      membranes remain poorly understood. The SNAREs syx and syb2 have transmembrane
      domains (TMDs) that can exert force directly on the lipid bilayers. The TMD of
      syx influences fusion pore flux in a manner that suggests it lines the nascent
      fusion pore through the plasma membrane. The TMD of syb2 traverses the vesicle
      membrane and is the most likely partner to syx in completing a proteinaceous
      fusion pore through the vesicle membrane, but the role of this vesicle SNARE in
      fusion pores has yet to be tested. Here amperometry and conductance measurements
      were performed to probe the function of the syb2 TMD in fusion pores formed
      during catecholamine exocytosis in mouse chromaffin cells. Fusion pore flux was
      sensitive to the size and charge of TMD residues near the N terminus; fusion pore
      conductance was altered by substitutions at these sites. Unlike syx, the syb2
      residues that influence fusion pore permeation fell along two alpha-helical faces
      of its TMD, rather than one. These results indicate a role for the syb2 TMD in
      nascent fusion pores, but in a very different structural arrangement from that of
      the syx TMD. 

PMID- 25855188
TI  - Facilitation of corticostriatal transmission following pharmacological inhibition
      of striatal phosphodiesterase 10A: role of nitric oxide-soluble guanylyl cyclase
      cGMP signaling pathways.
AB  - The striatum contains a rich variety of cyclic nucleotide phosphodiesterases
      (PDEs), which play a critical role in the regulation of cAMP and cGMP signaling.
      The dual-substrate enzyme PDE10A is the most highly expressed PDE in striatal
      medium-sized spiny neurons (MSNs) with low micromolar affinity for both cyclic
      nucleotides. Previously, we have shown that systemic and local administration of
      the selective PDE10A inhibitor TP-10 potently increased the responsiveness of
      MSNs to cortical stimulation. However, the signaling mechanisms underlying PDE10A
      inhibitor-induced changes in corticostriatal transmission are only partially
      understood. The current studies assessed the respective roles of cAMP and cGMP in
      the above effects using soluble guanylyl cyclase (sGC) or adenylate cyclase (AC)
      specific inhibitors. Cortically evoked spike activity was monitored in urethane
      anesthetized rats using in vivo extracellular recordings performed proximal to a
      microdialysis probe during local infusion of vehicle, the selective sGC inhibitor
      ODQ, or the selective AC inhibitor SQ 22536. Systemic administration of TP-10
      (3.2 mg/kg) robustly increased cortically evoked spike activity in a manner that
      was blocked following intrastriatal infusion of ODQ (50 MUm). The effects of TP
      10 on evoked activity were due to accumulation of cGMP, rather than cAMP, as the
      AC inhibitor SQ was without effect. Consistent with these observations, studies
      in neuronal NO synthase (nNOS) knock-out (KO) mice confirmed that PDE10A operates
      downstream of nNOS to limit cGMP production and excitatory corticostriatal
      transmission. Thus, stimulation of PDE10A acts to attenuate corticostriatal
      transmission in a manner largely dependent on effects directed at the NO-sGC-cGMP
      signaling cascade. 

PMID- 25855189
TI  - Mapping synapses by conjugate light-electron array tomography.
AB  - Synapses of the mammalian CNS are diverse in size, structure, molecular
      composition, and function. Synapses in their myriad variations are fundamental to
      neural circuit development, homeostasis, plasticity, and memory storage.
      Unfortunately, quantitative analysis and mapping of the brain's heterogeneous
      synapse populations has been limited by the lack of adequate single-synapse
      measurement methods. Electron microscopy (EM) is the definitive means to
      recognize and measure individual synaptic contacts, but EM has only limited
      abilities to measure the molecular composition of synapses. This report describes
      conjugate array tomography (AT), a volumetric imaging method that integrates
      immunofluorescence and EM imaging modalities in voxel-conjugate fashion. We
      illustrate the use of conjugate AT to advance the proteometric measurement of EM
      validated single-synapse analysis in a study of mouse cortex. 

PMID- 25855190
TI  - Upsilon spike-field coherence in a population of olfactory bulb neurons
      differentiates between odors irrespective of associated outcome.
AB  - Studies in different sensory systems indicate that short spike patterns within a
      spike train that carry items of sensory information can be extracted from the
      overall train by using field potential oscillations as a reference (Kayser et
      al., 2012; Panzeri et al., 2014). Here we test the hypothesis that the local
      field potential (LFP) provides the temporal reference frame needed to
      differentiate between odors regardless of associated outcome. Experiments were
      performed in the olfactory system of the mouse (Mus musculus) where the
      mitral/tufted (M/T) cell spike rate develops differential responses to rewarded
      and unrewarded odors as the animal learns to associate one of the odors with a
      reward in a go-no go behavioral task. We found that coherence of spiking in M/T
      cells with the Upsilon LFP (65 to 95 Hz) differentiates between odors regardless
      of the associated behavioral outcome of odor presentation. 

PMID- 25855191
TI  - Tonic firing rate controls dendritic Ca2+ signaling and synaptic gain in
      substantia nigra dopamine neurons.
AB  - Substantia nigra dopamine neurons fire tonically resulting in action potential
      backpropagation and dendritic Ca(2+) influx. Using Ca(2+) imaging in acute mouse
      brain slices, we find a surprisingly steep relationship between tonic firing rate
      and dendritic Ca(2+). Increasing the tonic rate from 1 to 6 Hz generated Ca(2+)
      signals up to fivefold greater than predicted by linear summation of single spike
      evoked Ca(2+)-transients. This "Ca(2+) supralinearity" was produced largely by
      depolarization of the interspike voltage leading to activation of subthreshold
      Ca(2+) channels and was present throughout the proximal and distal dendrites. Two
      photon glutamate uncaging experiments show somatic depolarization enhances NMDA
      receptor-mediated Ca(2+) signals >400 MUm distal to the soma, due to unusually
      tight electrotonic coupling of the soma to distal dendrites. Consequently, we
      find that fast tonic firing intensifies synaptically driven burst firing output
      in dopamine neurons. These results show that modulation of background firing rate
      precisely tunes dendritic Ca(2+) signaling and provides a simple yet powerful
      mechanism to dynamically regulate the gain of synaptic input. 

PMID- 25855192
TI  - Idiosyncratic brain activation patterns are associated with poor social
      comprehension in autism.
AB  - Autism spectrum disorder (ASD) features profound social deficits but neuroimaging
      studies have failed to find any consistent neural signature. Here we connect
      these two facts by showing that idiosyncratic patterns of brain activation are
      associated with social comprehension deficits. Human participants with ASD (N =
      17) and controls (N = 20) freely watched a television situation comedy (sitcom)
      depicting seminaturalistic social interactions ("The Office", NBC Universal) in
      the scanner. Intersubject correlations in the pattern of evoked brain activation
      were reduced in the ASD group-but this effect was driven entirely by five ASD
      subjects whose idiosyncratic responses were also internally unreliable. The
      idiosyncrasy of these five ASD subjects was not explained by detailed
      neuropsychological profile, eye movements, or data quality; however, they were
      specifically impaired in understanding the social motivations of characters in
      the sitcom. Brain activation patterns in the remaining ASD subjects were
      indistinguishable from those of control subjects using multiple multivariate
      approaches. Our findings link neurofunctional abnormalities evoked by
      seminaturalistic stimuli with a specific impairment in social comprehension, and
      highlight the need to conceive of ASD as a heterogeneous classification. 

PMID- 25855193
TI  - Neuronal LRP1 regulates glucose metabolism and insulin signaling in the brain.
AB  - Alzheimer's disease (AD) is a neurological disorder characterized by profound
      memory loss and progressive dementia. Accumulating evidence suggests that Type 2
      diabetes mellitus, a metabolic disorder characterized by insulin resistance and
      glucose intolerance, significantly increases the risk for developing AD. Whereas
      amyloid-beta (Abeta) deposition and neurofibrillary tangles are major
      histological hallmarks of AD, impairment of cerebral glucose metabolism precedes
      these pathological changes during the early stage of AD and likely triggers or
      exacerbates AD pathology. However, the mechanisms linking disturbed insulin
      signaling/glucose metabolism and AD pathogenesis remain unclear. The low-density
      lipoprotein receptor-related protein 1 (LRP1), a major apolipoprotein E receptor,
      plays critical roles in lipoprotein metabolism, synaptic maintenance, and
      clearance of Abeta in the brain. Here, we demonstrate that LRP1 interacts with
      the insulin receptor beta in the brain and regulates insulin signaling and
      glucose uptake. LRP1 deficiency in neurons leads to impaired insulin signaling as
      well as reduced levels of glucose transporters GLUT3 and GLUT4. Consequently,
      glucose uptake is reduced. By using an in vivo microdialysis technique sampling
      brain glucose concentration in freely moving mice, we further show that LRP1
      deficiency in conditional knock-out mice resulted in glucose intolerance in the
      brain. We also found that hyperglycemia suppresses LRP1 expression, which further
      exacerbates insulin resistance, glucose intolerance, and AD pathology. As loss of
      LRP1 expression is seen in AD brains, our study provides novel insights into
      insulin resistance in AD. Our work also establishes new targets that can be
      explored for AD prevention or therapy. 

PMID- 25855194
TI  - Prenatal drug exposure affects neonatal brain functional connectivity.
AB  - Prenatal drug exposure, particularly prenatal cocaine exposure (PCE), incurs
      great public and scientific interest because of its associated neurodevelopmental
      consequences. However, the neural underpinnings of PCE remain essentially
      uncharted, and existing studies in school-aged children and adolescents are
      confounded greatly by postnatal environmental factors. In this study, leveraging
      a large neonate sample (N = 152) and non-invasive resting-state functional
      magnetic resonance imaging, we compared human infants with PCE comorbid with
      other drugs (such as nicotine, alcohol, marijuana, and antidepressant) with
      infants with similar non-cocaine poly drug exposure and drug-free controls. We
      aimed to characterize the neural correlates of PCE based on functional
      connectivity measurements of the amygdala and insula at the earliest stage of
      development. Our results revealed common drug exposure-related connectivity
      disruptions within the amygdala-frontal, insula-frontal, and insula-sensorimotor
      circuits. Moreover, a cocaine-specific effect was detected within a subregion of
      the amygdala-frontal network. This pathway is thought to play an important role
      in arousal regulation, which has been shown to be irregular in PCE infants and
      adolescents. These novel results provide the earliest human-based functional
      delineations of the neural-developmental consequences of prenatal drug exposure
      and thus open a new window for the advancement of effective strategies aimed at
      early risk identification and intervention. 

PMID- 25855196
TI  - Central 5-HT neurotransmission modulates weight loss following gastric bypass
      surgery in obese individuals.
AB  - The cerebral serotonin (5-HT) system shows distinct differences in obesity
      compared with the lean state. Here, it was investigated whether serotonergic
      neurotransmission in obesity is a stable trait or changes in association with
      weight loss induced by Roux-in-Y gastric bypass (RYGB) surgery. In vivo cerebral
      5-HT2A receptor and 5-HT transporter binding was determined by positron emission
      tomography in 21 obese [four men; body mass index (BMI), 40.1 +/- 4.1 kg/m(2)]
      and 10 lean (three men; BMI, 24.6 +/- 1.5 kg/m(2)) individuals. Fourteen obese
      individuals were re-examined after RYGB surgery. First, it was confirmed that
      obese individuals have higher cerebral 5-HT2A receptor binding than lean
      individuals. Importantly, we found that higher presurgical 5-HT2A receptor
      binding predicted greater weight loss after RYGB and that the change in 5-HT2A
      receptor and 5-HT transporter binding correlated with weight loss after RYGB. The
      changes in the 5-HT neurotransmission before and after RYGB are in accordance
      with a model wherein the cerebral extracellular 5-HT level modulates the
      regulation of body weight. Our findings support that the cerebral 5-HT system
      contributes both to establish the obese condition and to regulate the body weight
      in response to RYGB. 

PMID- 25855195
TI  - Characterization of the transcriptome of nascent hair cells and identification of
      direct targets of the Atoh1 transcription factor.
AB  - Hair cells are sensory receptors for the auditory and vestibular system in
      vertebrates. The transcription factor Atoh1 is both necessary and sufficient for
      the differentiation of hair cells, and is strongly upregulated during hair-cell
      regeneration in nonmammalian vertebrates. To identify genes involved in hair cell
      development and function, we performed RNA-seq profiling of purified Atoh1
      expressing hair cells from the neonatal mouse cochlea. We identified >600
      enriched transcripts in cochlear hair cells, of which 90% have not been
      previously shown to be expressed in hair cells. We identified 233 of these hair
      cell genes as candidates to be directly regulated by Atoh1 based on the presence
      of Atoh1 binding sites in their regulatory regions and by analyzing Atoh1 ChIP
      seq datasets from the cerebellum and small intestine. We confirmed 10 of these
      genes as being direct Atoh1 targets in the cochlea by ChIP-PCR. The
      identification of candidate Atoh1 target genes is a first step in identifying
      gene regulatory networks for hair-cell development and may inform future studies
      on the potential role of Atoh1 in mammalian hair cell regeneration. 

PMID- 25855197
TI  - Sensitivity and specificity of linear array intraoperative ultrasound in
      glioblastoma surgery: a comparative study with high field intraoperative MRI and
      conventional sector array ultrasound.
AB  - INTRODUCTION: Linear array intraoperative ultrasound (lioUS) is an emerging
      technology for intracranial use. We evaluated sensitivity and specificity of
      lioUS to detect residual tumor in patients harboring a glioblastoma. METHODS:
      After near total resection in 20 patients, residual tumor detection using lioUS,
      conventional intraoperative ultrasound (cioUS), and gadopentetic
      diethylenetriamine penta-acetic acid (Gd-DTPA)-enhanced intraoperative MRI (iMRI)
      were compared. Sensitivity and specificity were calculated based on 68 navigated
      biopsies. Receiver operator characteristic (ROC) curves and correlation with
      histopathological findings of each imaging modality were calculated.
      Additionally, results were evaluated in the subgroup of recurrent disease (23
      biopsies in 8 patients). RESULTS: Sensitivity of lioUS (76 %) was significantly
      higher compared with iMRI (55 %) and cioUS (24 %). Specificity of lioUS (58 %)
      was significantly lower than in cioUS (96 %), while there was no significant
      difference to iMRI (74 %). All imaging modalities correlated significantly with
      histopathological findings. In the subgroup of recurrent disease, sensitivity and
      specificity decreased in all modalities. However, cioUS showed significant lower
      values than iMRI and lioUS. In ROC curves, lioUS showed a higher area und the
      curve (AUC) in comparison with iMRI and cioUS. We found similar results in the
      subgroup of recurrent disease. CONCLUSION: Tumor detection using a lioUS is
      significantly superior to cioUS. Overall test performance in lioUS is comparable
      with results of iMRI. While, the latter has a higher specificity and a
      significantly lower sensitivity in comparison with lioUS.

PMID- 25855198
TI  - Quantitative 31P-NMR spectroscopy for the determination of fosfomycin and
      impurity A in pharmaceutical products of fosfomycin sodium or calcium.
AB  - A quantitative 31P-NMR method for the determination of fosfomycin and impurity A
      in pharmaceutical products of fosfomycin sodium or calcium has been developed. In
      this method, coaxial inserts containing trimethyl phosphate are used as external
      standard. The method is convenient and robust, and gives both high accuracy and
      precision. It is shown that an accurate determination is possible using different
      probes and coaxial inserts.

PMID- 25855200
TI  - Smiling makes you look older.
AB  - People smile in social interactions to convey different types of nonverbal
      communication. However, smiling can potentially change the way a person is
      perceived along different facial dimensions, including perceived age. It is
      commonly assumed that smiling faces are perceived as younger than faces carrying
      a neutral expression. In the series of experiments reported here, I describe an
      unintuitive and robust effect in the opposite direction. Across different
      experimental conditions and stimulus sets, smiling faces were consistently
      perceived as older compared to neutral face photos of the same persons. I suggest
      that this effect is due to observer failure to ignore smile-associated wrinkles,
      mainly along the region of the eyes. These findings point to a misconception
      regarding the relationship between facial smile and perceived age and shed new
      light on the processes underlying human age perception. 

PMID- 25855199
TI  - alpha-2,8-Sialyltransferase Is Involved in the Development of Multidrug
      Resistance via PI3K/Akt Pathway in Human Chronic Myeloid Leukemia.
AB  - Cell surface sialylation is emerging as an important feature of cancer cell
      multidrug resistance (MDR). We have focused on the influence of 2,8
      sialyltransferases in key steps of the development of MDR in chronic myeloid
      leukemia (CML). The expressional profiles of six alpha-2,8-sialyltransferases
      were generated in three pairs of CML cell lines and peripheral blood mononuclear
      cells (PBMC) of CML patients. Cellular MDR phenotype positively correlated with
      ST8SIA4 and ST8SIA6 levels. Furthermore, ST8SIA4 mediated the activity of
      phosphoinositide-3 kinase (PI3K)/Akt signal pathway and the expression of P
      glycoprotein (P-gp). Targeting the PI3K/Akt pathway by its specific inhibitor
      LY294002, or by Akt RNA interfering reversed the MDR phenotype of K562/ADR cells.
      Inhibition of PI3K/Akt pathway also attenuated the effects caused by the
      overexpression of ST8SIA4 on MDR. Therefore this study indicated that alpha-2,8
      sialyltransferases involved in the development of MDR of CML cells probably
      through ST8SIA4 regulating the activity of PI3K/Akt signaling and the expression
      of P-gp.

PMID- 25855201
TI  - Context-dependent similarity effects in letter recognition.
AB  - In visual word recognition tasks, digit primes that are visually similar to
      letter string targets (e.g., 4/A, 8/B) are known to facilitate letter
      identification relative to visually dissimilar digits (e.g., 6/A, 7/B); in
      contrast, with letter primes, visual similarity effects have been elusive. In the
      present study we show that the visual similarity effect with letter primes can be
      made to come and go, depending on whether it is necessary to discriminate between
      visually similar letters. The results support a Bayesian view which regards
      letter recognition not as a passive activation process driven by the fixed
      stimulus properties, but as a dynamic evidence accumulation process for a
      decision that is guided by the task context. 

PMID- 25855202
TI  - When overlap leads to competition: Effects of phonological encoding on word
      duration.
AB  - Some accounts of acoustic reduction propose that variation in word duration is a
      reflection of the speaker's internal production processes, but it is unclear why
      lengthening within a word benefits planning. The present study examines whether
      variability in word length is partly attributable to phonological encoding. In an
      event-description task, speakers produced words with longer durations when the
      word shared part of its phonology with a previously articulated word than when it
      did not. More importantly, lengthening was greater when the overlap was word
      initial than when it was word-final. These differences in duration are in line
      with predictions of serial phonological competition models, which claim that
      words that overlap in onsets create more competition than words that overlap in
      offsets and are thus more difficult to produce. That word duration is sensitive
      to differences in production difficulty suggests a link between speakers'
      duration choices and phonological encoding. We propose that lengthening provides
      the production system with the necessary processing time to produce a word's
      sounds. 

PMID- 25855203
TI  - Evaluation of measurement errors of temperature and relative humidity from HOBO
      data logger under different conditions of exposure to solar radiation.
AB  - This study aimed to assess measurements of temperature and relative humidity
      obtained with HOBO a data logger, under various conditions of exposure to solar
      radiation, comparing them with those obtained through the use of a
      temperature/relative humidity probe and a copper-constantan thermocouple
      psychrometer, which are considered the standards for obtaining such measurements.
      Data were collected over a 6-day period (from 25 March to 1 April, 2010), during
      which the equipment was monitored continuously and simultaneously. We employed
      the following combinations of equipment and conditions: a HOBO data logger in
      full sunlight; a HOBO data logger shielded within a white plastic cup with
      windows for air circulation; a HOBO data logger shielded within a gill-type
      shelter (multi-plate prototype plastic); a copper-constantan thermocouple
      psychrometer exposed to natural ventilation and protected from sunlight; and a
      temperature/relative humidity probe under a commercial, multi-plate radiation
      shield. Comparisons between the measurements obtained with the various devices
      were made on the basis of statistical indicators: linear regression, with
      coefficient of determination; index of agreement; maximum absolute error; and
      mean absolute error. The prototype multi-plate shelter (gill-type) used in order
      to protect the HOBO data logger was found to provide the best protection against
      the effects of solar radiation on measurements of temperature and relative
      humidity. The precision and accuracy of a device that measures temperature and
      relative humidity depend on an efficient shelter that minimizes the interference
      caused by solar radiation, thereby avoiding erroneous analysis of the data
      obtained. 

PMID- 25855204
TI  - Heavy metals (Cd, Co, Cu, Ni, Pb, Fe, and Hg) content in four fish commonly
      consumed in Iran: risk assessment for the consumers.
AB  - In this study, concentrations of Cd, Co, Cu, Ni, Pb, Fe, and Hg were determined
      in commercially valuable fish from Khuzestan shore, northwest of the Persian
      Gulf. It was also our intention to evaluate potential risks to human health
      associated with seafood consumption. The liver and skin showed higher metal
      concentrations than the muscle. The results showed that heavy metal
      concentrations in different food habitats increase in the following order:
      benthic omnivorous fish < zooplanktivore fish < phytoplanktivore fish < piscivore
      fish. Also, the comparison indicated that benthic species (Euryglossa orientalis,
      Otolithes ruber) were more contaminated than pelagic species (Liza abu and
      Psettodes erumei). Therefore, the concentration of heavy metals in edible part of
      fish species did not exceed the permissible limits proposed by Food and
      Agriculture Organization (FAO) (1983), WHO (1996), Regional Organization for the
      Protection of the Marine Environment (ROPME) (1999), and FAD (2001) which are
      suitable for human consumption, except for Ni and Cd in E. orientalis and Pb in
      O. ruber. 

PMID- 25855205
TI  - Simultaneous quantification of six major triterpenoid saponins in Schefflera
      kwangsiensis using high-performance liquid chromatography coupled to orbitrap
      mass spectrometry.
AB  - A simple and accurate analytical method was developed for simultaneous and
      quantitative analysis of six triterpenoid saponins in Schefflera kwangsiensis via
      high-performance liquid chromatography (HPLC) with mass spectrometry (MS) in this
      study. Separation was performed on a Thermo hypersil GOLD C18 column (150 mm *
      2.1 mm, 5 MUm). A mobile phase consisting of methanol/acetonitrile/8 mM ammonium
      acetate in water was used with a flow rate of 0.3 mL/min. The analytes were
      detected by MS with the electrospray ionisation (ESI) source combined with
      negative monitoring and full scan mode, and were analysed by extracted ion
      chromatography. This established HPLC-ESI-MS analysis demonstrated good
      linearity, sensitivity, stability, precision, accuracy and recovery. Therefore,
      this analytical method has great potential to be a novel tool to qualify S.
      kwangsiensis.

PMID- 25855206
TI  - Functional study of a salt-inducible TaSR gene in Triticum aestivum.
AB  - The gene expression chip of a salt-tolerant wheat mutant under salt stress was
      used to clone a salt-induced gene with unknown functions. This gene was
      designated as TaSR (Triticum aestivum salt-response gene) and submitted to
      GenBank under accession number EF580107. Quantitative polymerase chain reaction
      (PCR) analysis showed that gene expression was induced by salt stress.
      Arabidopsis and rice (Oryza sativa) plants expressing TaSR presented higher salt
      tolerance than the controls, whereas AtSR mutant and RNA interference rice plants
      were more sensitive to salt. Under salt stress, TaSR reduced Na(+) concentration
      and improved cellular K(+) and Ca(2+) concentrations; this gene was also
      localized on the cell membrane. beta-Glucuronidase (GUS) staining and GUS
      fluorescence quantitative determination were conducted through fragmentation
      cloning of the TaSR promoter. Salt stress-responsive elements were detected at
      588-1074 bp upstream of the start codon. GUS quantitative tests of the full
      length promoter in different tissues indicated that promoter activity was highest
      in the leaf under salt stress. Bimolecular fluorescence complementation and yeast
      two-hybrid screening further showed the correlation of TaSR with TaPRK and TaKPP.
      In vitro phosphorylation of TaSR and TaPRK2697 showed that TaPRK2697 did not
      phosphorylate TaSR. This study revealed that the novel TaSR may be used to
      improve plant tolerance to salt stress. 

PMID- 25855207
TI  - Mini-Addenbrooke's Cognitive Examination: a pragmatic diagnostic accuracy study.

PMID- 25855208
TI  - Training on dementia for emergency ambulance staff: research agenda and
      opportunities.

PMID- 25855209
TI  - Analysis of green algal growth via dynamic model simulation and process
      optimization.
AB  - Chlamydomonas reinhardtii is a green microalga with the potential to generate
      sustainable biofuels for the future. Process simulation models are required to
      predict the impact of laboratory-scale growth experiments on future scaled-up
      system operation. Two dynamic models were constructed to simulate C. reinhardtii
      photo-autotrophic and photo-mixotrophic growth. A novel parameter estimation
      methodology was applied to determine the values of key parameters in both models,
      which were then verified using experimental results. The photo-mixotrophic model
      was used to accurately predict C. reinhardtii growth under different light
      intensities and in different photobioreactor configurations. The optimal
      dissolved CO2 concentration for C. reinhardtii photo-autotrophic growth was
      determined to be 0.0643 g.L(-1) , and the optimal light intensity for algal
      growth was 47 W.m(-2) . Sensitivity analysis revealed that the primary factor
      limiting C. reinhardtii growth was its intrinsic cell decay rate rather than
      light attenuation, regardless of the growth mode. The photo-mixotrophic growth
      model was also applied to predict the maximum biomass concentration at different
      flat-plate photobioreactors scales. A double-exposure-surface photobioreactor
      with a lower light intensity (less than 50 W.m(-2) ) was the best configuration
      for scaled-up C. reinhardtii cultivation. Three different short-term (30-day) C.
      reinhardtii photo-mixotrophic cultivation processes were simulated and optimised.
      The maximum biomass productivity was 0.053 g.L(-1) .hr(-1) , achieved under
      continuous photobioreactor operation. The continuous stirred-tank reactor was the
      best operating mode, as it provides both the highest biomass productivity and
      lowest electricity cost of pump operation.

PMID- 25855210
TI  - Photosensitive functionalized surface-modified quantum dots for polymeric
      structures via two-photon-initiated polymerization technique.
AB  - In this paper, the surface modification of CdSe- and CdZnS-based quantum dots
      (QDs) with a functional silica shell is reported. Functionalized silica shells
      are prepared by two routes: either by ligand exchange and a modified Stober
      process or by a miniemulsion process with amphiphilic poly(oxyethylene)
      nonylphenylether also know as Igepal CO-520 (IG) as oligomeric amphiphile and
      modified silica precursors. The polymerizable groups on the functionalized silica
      shell allow covalent bonding to a polymer matrix and prevent demixing during
      polymerization and crosslinking. This allows the homogeneous incorporation of QDs
      in a crosslinked polymer matrix. This paper furthermore demonstrates that the
      resulting QDs, which are i) shielded with a proper silica shell and ii)
      functionalized with crosslinkable groups, can be used in two-photon-initiated
      polymerization processes in combination with different photoresists to obtain
      highly luminescent 3D structures. The resulting luminescent structures are
      attractive candidates for photonics and metamaterials research.

PMID- 25855212
TI  - Multidimensional profiles of health locus of control in Hispanic Americans.
AB  - Latent profile analysis identified health locus of control profiles among 436
      Hispanic Americans who completed the Multidimensional Health Locus of Control
      scales. Results revealed four profiles: Internally Oriented-Weak, -Moderate, 
      Strong, and Externally Oriented. The profile groups were compared on
      sociocultural and demographic characteristics, health beliefs and behaviors, and
      physical and mental health outcomes. The Internally Oriented-Strong group had
      less cancer fatalism, religiosity, and equity health attributions, and more
      alcohol consumption than the other three groups; the Externally Oriented group
      had stronger equity health attributions and less alcohol consumption. Deriving
      multidimensional health locus of control profiles through latent profile analysis
      allows examination of the relationships of health locus of control subtypes to
      health variables.

PMID- 25855211
TI  - Palliative care for patients with end-stage liver disease.
AB  - Liver disease results in over four million physician visits and over 750,000
      hospitalizations per year in the USA. Those with chronic liver disease frequently
      progress to cirrhosis, end-stage liver disease (ESLD), and death. Patients with
      ESLD experience numerous complications, including muscle cramps, confusion
      (hepatic encephalopathy), protein calorie malnutrition, muscle wasting, fluid
      overload (ascites, edema), bleeding (esophagogastric variceal hemorrhage),
      infection (spontaneous bacterial peritonitis), fatigue, anxiety, and depression.
      Despite significant improvements in palliation of these complications, patients
      still suffer reduced quality of life and must confront the fact that their
      disease will often inexorably progress to death. Liver transplantation is a valid
      option in this setting, increasing the duration of survival and palliating many
      of the symptoms. However, many patients die waiting for an organ or are not
      candidates for transplantation due to comorbid illness. Others receive a
      transplant but succumb to complications of the transplant itself. Patients and
      families must struggle with simultaneously hoping for a cure while facing a life
      threatening illness. Ideally, the combination of palliative care with life
      sustaining therapy can maximize the patients' quality and quantity of life. If it
      becomes clear that life-sustaining therapy is no longer an option, these patients
      are then already in a system to help them with end-of-life care. 

PMID- 25855213
TI  - Characteristics of Bacillus sp. PZ-1 and its biosorption to Pb(II).
AB  - During the long and cold winter season in northern area of China, wastewater
      treatment is often inefficient which causes the substandard discharge. In this
      study, a lead-resistant psychrotrophilic bacterium was isolated and used as an
      adsorbent to remove Pb(II) from aqueous solution at 15  degrees C. The strain was
      identified and designated as Bacillus sp. PZ-1 based on the morphology,
      physiological-biochemical experiments and 16S rDNA sequence analysis. The minimal
      inhibitory concentration and antibiotic experiments revealed that PZ-1 had high
      resistance to 1500 mg L(-1) of Zn(II), 800 mg L(-1) of Cu(II), 400 mg L(-1) of
      Ni(II), 15 ug mL(-1) of chloramphenicol and 50 ug mL(-1) of streptomycin, but
      susceptibility to 200 mg L(-1) of Co(II). Scanning electron microscopy, energy
      dispersive X-ray spectroscopy and atomic force microscopy analyses showed that
      biosorption of Bacillus sp. PZ-1 to Pb(II) involved surface adsorption, ion
      exchange and micro-precipitate. Fourier transform infrared spectroscopy analyses
      indicated that hydroxyl, carbonyl and carboxyl on cells may play vital roles in
      Pb(II) adsorption. Besides, siderophore secreted by PZ-1 had beneficial impacts
      on the Pb(II) removal. Biosorption experiments were carried out as a function of
      initial Pb(II) concentration (50-500 mg L(-1)), pH (3.0-7.0), biomass
      concentration (5-50 g L(-1)) and contact time (5-40 min). Biosorption rate of
      93.01% with adsorption capacity of 9.30 mg g(-1) was obtained under the initial
      Pb(II) concentration of 400 mg (-1), pH of 5.0, contact time of 20 min, biomass
      concentration of 40 g L(-1) and the temperature of 15  degrees C. The equilibrium
      data were well fitted with Langmuir model, which indicated the adsorption process
      of Pb(II) is monolayer adsorption. Bacillus sp. PZ-1 appeared to be an efficient
      biosorbent for removing Pb(II) from wastewater at low temperature.

PMID- 25855214
TI  - Cost analysis of prophylaxis with activated prothrombin complex concentrate vs.
      on-demand therapy with activated factor VII in severe haemophilia A patients with
      inhibitors, in Spain.
AB  - OBJECTIVE: A cost analysis model was developed to compare annual cost of
      prophylaxis with activated prothrombin complex concentrate (aPCC) vs. on-demand
      therapy with activated recombinant factor VII (rFVIIa) in severe haemophilia A
      patients with inhibitors for the Spanish National Health System (NHS). METHODS:
      Model inputs were drug cost for prophylaxis (aPCC) and for on-demand treatment
      (rFVIIa or aPCC); bleeding episodes management (excluding bypassing agent cost);
      surgical costs and disease management (excluding bleeding episodes). Annual
      bleeding episodes treated on-demand was assumed to be 25, whereas breakthrough
      bleeds on prophylaxis was 8. Dose for prophylaxis was 75.72 U kg(-1) , three
      times per week. The total on-demand dose/bleeding episode was 679.66 MUg kg(-1)
      (rFVIIa) and 235.28 U kg(-1) (aPCC). The average bleeding cost (?2998) considered
      different bleeding sites (62.5% joints, 28.6% muscles and soft tissues, 3.6%
      mucocutaneous tissues and 5.4% other areas). A 7.5% deduction was applied to ex
      factory drug prices. Unitary costs (?2013) derived from local databases.
      Sensitivity analyses (SA) were performed. RESULTS: Annual cost of aPCC
      prophylaxis (?524,358) was 16% lower than on-demand treatment with rFVIIa
      (?627,876). Yearly drug costs were ?497,017 for aPCC (?73,166 for on-demand
      treatment and ?423,850 for prophylaxis), and ?548,870 for rFVIIa. Disease
      management cost (?2645 per year) and surgical procedures (?708 per year) were
      common for both strategies. In the SA prophylactic treatment led to savings
      between ?26,225 and ?-1,008,960. CONCLUSION: Prophylaxis with aPCC reduces number
      of bleeding episodes in severe haemophilia A patients with inhibitors. aPCC
      prophylaxis resulted in savings in excess of ?100,000 per-patient per year, being
      16% less costly than on-demand treatment with rFVIIa, for the Spanish NHS.

PMID- 25855215
TI  - Fifteen-minute consultation: A child with toe walking.
AB  - Toe walking is a common developmental phenomenon in young children. It is usually
      benign and self-limiting. Toe walking can be a presenting sign of some serious
      underlying disorders and idiopathic toe walking is a diagnosis of exclusion.
      Persistent toe walking can lead to limited ankle dorsiflexion which may cause
      functional problems. Specific interventions depend on underlying cause and may
      range from verbal reinforcement to serial casting and surgery. 

PMID- 25855216
TI  - Fifteen-minute consultation: The child with short stature.
AB  - Short stature can be a cause of distress for children and families. It is not
      usually pathological, but it is important to identify treatable conditions. This
      article presents a systematic approach to the evaluation of a child with short
      stature, covering differential diagnoses, first line investigations and
      indications for treatment with growth hormone. 

PMID- 25855217
TI  - Controllability analysis of transcriptional regulatory networks reveals circular
      control patterns among transcription factors.
AB  - Transcriptional regulation is the most committed type of regulation in living
      cells where transcription factors (TFs) control the expression of their target
      genes and TF expression is controlled by other TFs forming complex
      transcriptional regulatory networks that can be highly interconnected. Here we
      analyze the topology and organization of nine transcriptional regulatory networks
      for E. coli, yeast, mouse and human, and we evaluate how the structure of these
      networks influences two of their key properties, namely controllability and
      stability. We calculate the controllability for each network as a measure of the
      organization and interconnectivity of the network. We find that the number of
      driver nodes nD needed to control the whole network is 64% of the TFs in the E.
      coli transcriptional regulatory network in contrast to only 17% for the yeast
      network, 4% for the mouse network and 8% for the human network. The high
      controllability (low number of drivers needed to control the system) in yeast,
      mouse and human is due to the presence of internal loops in their regulatory
      networks where the TFs regulate each other in a circular fashion. We refer to
      these internal loops as circular control motifs (CCM). The E. coli
      transcriptional regulatory network, which does not have any CCMs, shows a
      hierarchical structure of the transcriptional regulatory network in contrast to
      the eukaryal networks. The presence of CCMs also has influence on the stability
      of these networks, as the presence of cycles can be associated with potential
      unstable steady-states where even small changes in binding affinities can cause
      dramatic rearrangements of the state of the network.

PMID- 25855218
TI  - Protic-salt-derived nitrogen/sulfur-codoped mesoporous carbon for the oxygen
      reduction reaction and supercapacitors.
AB  - Nitrogen/sulfur-co-doped mesoporous carbon (Phen-HS) was obtained through direct
      carbonization of a single protic salt, that is, 1,10-phenanthrolinium dibisulfate
      ([Phen][2 HSO4 ]), in the presence of a colloidal silica template without the use
      of additional acid or metal catalysts for prepolymerization prior to
      carbonization. Phen-HS was prepared in a relatively high yield (30.0 %) and has a
      large surface area (1161 m(2)  g(-1) ), large pore volume (2.490 cm(3)  g(-1) ),
      large mesopores (~12 nm), narrow pore-size distribution (7-16 nm), and high
      nitrogen (7.5 at %) and sulfur (1.3 at %) contents. The surface area/pore-size
      distribution is much higher/narrower than that of most reported carbon materials
      obtained from traditional precursors by using the same template. Phen-HS was
      directly used as an electrocatalyst for the oxygen reduction reaction (ORR) and
      as an electrode material for supercapacitors. As an efficient metal-free
      catalyst, Phen-HS exhibited good electrocatalytic activity toward the ORR in a
      0.1 M KOH aqueous solution, which is comparable to the activity of a commercial
      Pt/C catalyst. Electrochemical measurements for Phen-HS used in a double-layer
      capacitor showed high specific capacitances of 160 and 140 F g(-1) in 1 M H2 SO4
      and 6 M KOH, respectively, with good rate capabilities and high cycling
      stabilities. 

PMID- 25855219
TI  - The management of risk arising from the use of antimicrobial agents in veterinary
      medicine in EU/EEA countries - a review.
AB  - Antimicrobials are essential medicines for the treatment of many microbial
      infections in humans and animals. Only a small number of antimicrobial agents
      with new mechanisms of action have been authorized in recent years for use in
      either humans or animals. Antimicrobial resistance (AMR) arising from the use of
      antimicrobial agents in veterinary medicine is a concern for public health due to
      the detection of increasing levels of resistance in foodborne zoonotic bacteria,
      particularly gram-negative bacteria, and due to the detection of determinants of
      resistance such as Extended-spectrum beta-lactamases (ESBL) in bacteria from
      animals and in foodstuffs of animal origin. The importance and the extent of the
      emergence and spread of AMR from animals to humans has yet to be quantified.
      Likewise, the relative contribution that the use of antimicrobial agents in
      animals makes to the overall risk to human from AMR is currently a subject of
      debate that can only be resolved through further research. Nevertheless, risk
      managers have agreed that the impact on public health of the use of
      antimicrobials in animals should be minimized as far as possible and a variety of
      measures have been introduced by different authorities in the EU to achieve this
      objective. This article reviews a range of measures that have been implemented
      within European countries to reduce the occurrence and the risk of transmission
      of AMR to humans following the use of antimicrobial agents in animals and briefly
      describes some of the alternatives to the use of antimicrobial agents that are
      being developed. 

PMID- 25855221
TI  - Polypyridyl Ru(II)-derivatized polypropylacrylate polymer with a terminal water
      oxidation catalyst. Application of reversible addition-fragmentation chain
      transfer polymerization.
AB  - A Ru(II) polypyridyl-derivatized polypropylacrylate end-capped with a water
      oxidation-catalyst (WOC) has been synthesized by using reversible addition
      fragmentation chain transfer polymerization (RAFT) followed by click reaction and
      end-group functionalization. In cyclic voltammograms in propylene carbonate,
      chromophore oxidation occurs at 1.27 V vs. NHE and the Ru(III/II) wave for the
      catalyst at 0.84 V vs. NHE. Upon excitation of the Ru(II) chromophore, excited
      state energy migration occurs by site-to-site, -Ru(II)*- -> -Ru(II)-, energy
      transfer hopping along the polymer chain, in part, reaching the terminal catalyst
      site where -Ru(II)*- -> -Ru(II)-OH2(2+) energy transfer is favored by DeltaG(en)
      = -2100 cm(-1). Added MV(2+) as an electron transfer acceptor oxidizes the 
      Ru(II)*- excited state on the polymer to Ru(III), -Ru(II)*- + MV(2+) -> -Ru(III)-
      + MV(+), and ultimately, the catalyst, by site-to-site electron transfer hopping
      and oxidation, [Formula: see text]. Oxidation is followed by relatively slow,
      diffusional back electron transfer from MV(+) to Ru(III) sites on the polymer
      chain. The mixed chromophore-catalyst polymer is a water oxidation catalyst with
      potential for enhanced light harvesting and water oxidation.

PMID- 25855220
TI  - Plasma extracellular superoxide dismutase concentration, allelic variations in
      the SOD3 gene and risk of myocardial infarction and all-cause mortality in people
      with type 1 and type 2 diabetes.
AB  - BACKGROUND: Oxidative stress is involved in development of diabetes
      complications. Extracellular superoxide dismutase (EC-SOD, SOD3) is a major
      extracellular antioxidant enzyme and is highly expressed in arterial walls.
      Advanced oxidation protein products (AOPP) and 8-iso-prostaglandin (isoprostane)
      are markers of oxidative stress. We investigated association of SOD3 gene
      variants, plasma concentrations of EC-SOD, AOPP and isoprostane with myocardial
      infarction and mortality in diabetic patients. METHODS: We studied three cohorts
      designed to evaluate the vascular complications of diabetes: the GENEDIAB study
      (469 participants with type 1 diabetes at baseline; follow-up data for 259
      participants), the GENESIS study (603 participants with type 1 diabetes at
      baseline; follow-up data for 525 participants) and the DIABHYCAR study (3137
      participants with type 2 diabetes at baseline and follow-up). Duration of follow
      up was 9, 5, and 5 years, respectively. Main outcome measures were incidence of
      myocardial infarction, and cardiovascular and total mortality during follow-up.
      Six single nucleotide polymorphisms in the SOD3 locus were genotyped in the three
      cohorts. Plasma concentrations of EC-SOD, AOPP, and isoprostane were measured in
      baseline samples of GENEDIAB participants. RESULTS: In GENEDIAB/GENESIS pooled
      cohorts, the minor T-allele of rs2284659 variant was inversely associated with
      the prevalence at baseline (Odds Ratio 0.48, 95% CI 0.29-0.78, p = 0.004) and the
      incidence during follow-up of myocardial infarction (Hazard Ratio 0.58, 95% CI
      0.40-0.83, p = 0.003) and with cardiovascular (HR 0.33, 95% CI 0.08-0.74, p =
      0.004) and all-cause mortality (HR 0.44, 95% CI 0.21-0.73, p = 0.0006). The
      protective allele was associated with higher plasma EC-SOD and lower plasma AOPP
      concentrations in GENEDIAB. It was also inversely associated with incidence of
      myocardial infarction (HR 0.75, 95% CI 0.59-0.94, p = 0.01) and all-cause
      mortality (HR 0.87, 95% CI 0.79-0.97, p = 0.008) in DIABHYCAR. CONCLUSIONS: The T
      allele of rs2284659 in the promoter of SOD3 was associated with a more favorable
      plasma redox status and with better cardiovascular outcomes in diabetic patients.
      Our results suggest that EC-SOD plays an important role in the mechanisms of
      vascular protection against diabetes-related oxidative stress.

PMID- 25855222
TI  - Alogliptin: a review of its use in patients with type 2 diabetes mellitus.
AB  - The dipeptidyl peptidase-4 inhibitor alogliptin (Nesina(r), Vipidia(r)) is
      approved in numerous countries worldwide for the treatment of type 2 diabetes
      mellitus. Fixed-dose combinations of alogliptin/metformin (Kazano(r),
      Vipdomet(r)) and alogliptin/pioglitazone (Oseni(r), Incresync(r)) are also
      available. This article reviews the clinical efficacy and tolerability of oral
      alogliptin in the treatment of type 2 diabetes. Results of randomized controlled
      trials demonstrated that oral alogliptin improved glycaemic control when
      administered as monotherapy, as dual therapy in combination with metformin,
      pioglitazone, a sulfonylurea, voglibose or insulin, or as triple therapy in
      combination with metformin plus pioglitazone. Alogliptin was generally well
      tolerated in patients with type 2 diabetes and was weight neutral, with a low
      risk of hypoglycaemia. Results of the large, well designed EXAMINE trial revealed
      that alogliptin was not associated with an increased risk of major cardiovascular
      events in patients with type 2 diabetes and recent acute coronary syndrome. In
      conclusion, alogliptin is a useful option for the treatment of patients with type
      2 diabetes.

PMID- 25855224
TI  - Emerging directions in the study of the ecology and evolution of plant-animal
      mutualistic networks: a review.
AB  - The study of mutualistic plant and animal networks is an emerging field of
      ecological research. We reviewed progress in this field over the past 30 years.
      While earlier studies mostly focused on network structure, stability, and
      biodiversity maintenance, recent studies have investigated the conservation
      implications of mutualistic networks, specifically the influence of invasive
      species and how networks respond to habitat loss. Current research has also
      focused on evolutionary questions including phylogenetic signal in networks,
      impact of networks on the coevolution of interacting partners, and network
      influences on the evolution of interacting species. We outline some directions
      for future research, particularly the evolution of specialization in mutualistic
      networks, and provide concrete recommendations for environmental managers. 

PMID- 25855225
TI  - Species identification refined by molecular scatology in a community of sympatric
      carnivores in Xinjiang, China.
AB  - Many ecological studies and conservation management plans employ noninvasive scat
      sampling based on the assumption that species' scats can be correctly identified
      in the field. However, in habitats with sympatric similarly sized carnivores,
      misidentification of scats is frequent and can lead to bias in research results.
      To address the scat identification dilemma, molecular scatology techniques have
      been developed to extract DNA from the donor cells present on the outer lining of
      the scat samples. A total of 100 samples were collected in the winter of 2009 and
      2011 in Taxkorgan region of Xinjiang, China. DNA was extracted successfully from
      88% of samples and genetic species identification showed that more than half the
      scats identified in the field as snow leopard (Panthera uncia) actually belonged
      to fox (Vulpes vulpes). Correlation between scat characteristics and species were
      investigated, showing that diameter and dry weight of the scat were significantly
      different between the species. However it was not possible to define a precise
      range of values for each species because of extensive overlap between the
      morphological values. This preliminary study confirms that identification of snow
      leopard feces in the field is misleading. Research that relies upon scat samples
      to assess distribution or diet of the snow leopard should therefore employ
      molecular scatology techniques. These methods are financially accessible and
      employ relatively simple laboratory procedures that can give an indisputable
      response to species identification from scats. 

PMID- 25855226
TI  - Effect of food restriction on the energy metabolism of the Chinese bulbul
      (Pycnonotus sinensis).
AB  - Food resources play an important role in the regulation of animals' physiology
      and behavior. We investigated the effect of short-term food restriction on
      metabolic thermogenesis of Chinese bulbuls (Pycnonotus sinensis) by measuring
      changes in body mass, body fat, basic metabolic rate (BMR), and organ mass of
      wild-caught Chinese bulbuls from Wenzhou, China. Short-term food restriction
      induced a significant decrease in body mass and body fat but body mass returned
      to normal levels soon after food was no longer restricted. Food restriction
      caused a significant reduction in BMR after 7 days (P<0.05), which returned to
      normal levels after food restriction ceased. Log total BMR was positively
      correlated with log body mass (r(2)=0.126, P<0.05). The dry masses of livers and
      the digestive tract were higher in birds that had been subject to temporary food
      restriction than in control birds and those subject to continual food restriction
      (P<0.001 and P<0.05, respectively). There was also significant differences in the
      dry mass of the lungs (P<0.05), heart (P<0.01), and spleen (P<0.05) in birds
      subject to short-term food restriction compared to control birds and those
      subject to continual food restriction. BMR was positively correlated with body
      and organ (heart, kidney and stomach) mass. These results suggest that the
      Chinese bulbul adjusts to restricted food availability by utilizing its energy
      reserves, lowering its BMR and changing the weight of various internal organs so
      as to balance total energy requirements. These may all be survival strategies
      that allow birds to cope with unpredictable variation in food abundance. 

PMID- 25855227
TI  - Diversity and habitat association of small mammals in Aridtsy forest, Awi Zone,
      Ethiopia.
AB  - Here, we conducted a survey to examine the diversity, distribution and habitat
      association of small mammals from August 2011 to February 2012 incorporating both
      wet and dry seasons in Aridtsy forest, Awi Zone, Ethiopia. Using Sherman live
      traps and snap traps in four randomly selected trapping grids, namely, natural
      forest, bushland, grassland and farmland, a total of 468 individuals comprising
      eight species of small mammals (live traps) and 89 rodents of six species (snap
      traps) were trapped in 2352 and 1200 trap nights, respectively. The trapped small
      mammals included seven rodents and one insectivore: Lophuromys flavopuntatus
      (30.6%), Arvicanthis dembeensis (25.8%), Stenocephalemys albipes (20%), Mastomys
      natalensis (11.6%), Pelomys harringtoni (6.4%), Acomys cahirinus (4.3%),
      Lemniscomys zebra (0.2%) and the greater red musk shrew (Crocidura flavescens,
      1.1%). Analysis showed statistically significant variations in the abundance and
      habitat preferences of small mammals between habitats during wet and dry seasons.

PMID- 25855228
TI  - Energy intake, oxidative stress and antioxidant in mice during lactation.
AB  - Reproduction is the highest energy demand period for small mammals, during which
      both energy intake and expenditure are increased to cope with elevated energy
      requirements of offspring growth and somatic protection. Oxidative stress life
      history theory proposed that reactive oxygen species (ROS) were produced in
      direct proportion to metabolic rate, resulting in oxidative stress and damage to
      macromolecules. In the present study, several markers of oxidative stress and
      antioxidants activities were examined in brain, liver, kidneys, skeletal muscle
      and small intestine in non-lactating (Non-Lac) and lactating (Lac) KM mice.
      Uncoupling protein (ucps) gene expression was examined in brain, liver and
      muscle. During peak lactation, gross energy intake was 254% higher in Lac mice
      than in Non-Lac mice. Levels of H2O2 of Lac mice were 17.7% higher in brain
      (P<0.05), but 21.1% (P<0.01) and 14.5% (P<0.05) lower in liver and small
      intestine than that of Non-Lac mice. Malonadialdehyde (MDA) levels of Lac mice
      were significantly higher in brain, but lower in liver, kidneys, muscle and small
      intestine than that of Non-Lac mice. Activity of glutathione peroxidase (GSH-PX)
      was significantly decreased in brain and liver in the Lac group compared with
      that in the Non-Lac group. Total antioxidant capacity (T-AOC) activity of Lac
      mice was significantly higher in muscle, but lower in kidneys than Non-Lac mice.
      Ucp4 and ucp5 gene expression of brain was 394% and 577% higher in Lac mice than
      in Non-Lac mice. These findings suggest that KM mice show tissue-dependent
      changes in both oxidative stress and antioxidants. Activities of antioxidants may
      be regulated physiologically in response to the elevated ROS production in
      several tissues during peak lactation. Regulations of brain ucp4 and ucp5 gene
      expression may be involved in the prevention of oxidative damage to the tissue. 

PMID- 25855229
TI  - Sex differences in morphine-induced behavioral sensitization and social behaviors
      in ICR mice.
AB  - Gender and genetic strain are two prominent variants that influence drug abuse.
      Although certain sex-related behavioral responses have been previously
      characterized in ICR mice, little is known about the effects of sex on morphine
      induced behavioral responses in this outbred strain. Therefore, in this study, we
      investigated the sex differences of morphine-induced locomotion, anxiety-like and
      social behaviors in ICR mice. After morphine or saline exposure for four
      consecutive days (twice daily), increased locomotion, more time spent in the
      central area, as well as attenuated rearing and self-grooming behaviors were
      found in morphine-treated females in an open field; no differences were found in
      locomotion and the time spent in the central area between male and female
      controls. When interacting with the same-sex individuals, female controls were
      engaged in more social investigation, following, body contacting and self
      grooming behaviors than controls; morphine exposure reduced contacting and self
      grooming behaviors in females; in contrast, these effects were not found in
      males. These results indicate that female ICR mice are more prosocial and are
      more susceptible to morphine exposure than males. 

PMID- 25855230
TI  - The validity of Sarcocystis sinensis.

PMID- 25855232
TI  - Three Australian leg-flagged Great Knots (Calidris tenuirostris) found on the
      islet coast of Jinmen (Quimoy) in Fujian, China.

PMID- 25855231
TI  - Absence of mutation in miR-34a gene in a Chinese longevity population.

PMID- 25855234
TI  - Psychosexual Well-Being after Childhood Surgery for Anorectal Malformation or
      Hirschsprung's Disease.
AB  - INTRODUCTION: Anorectal malformations (ARMs) and Hirschsprung's disease (HD) are
      congenital malformations requiring pelvic floor surgery in early childhood, with
      possible sequelae for psychosexual development. AIMS: To assess psychosexual well
      being in adult ARM and HD patients related to health-related quality of life.
      METHODS: Eligible for this cross-sectional two-center study were all patients
      aged >=18 years who had been operated for ARM or HD. Exclusion criteria were
      intellectual disability, comorbidity affecting sexual functioning, and cloacal
      malformation. MAIN OUTCOME MEASURES: Participants completed the International
      Index of Erectile Functioning, Female Sexual Functioning Index, Female Sexual
      Distress Scale, Hirschsprung and Anorectal Malformation Quality of Life
      Questionnaire, and sexual education questionnaire. RESULTS: Response rates were
      32% and 37% for ARM and HD patients, respectively. We studied 70 participating
      ARM and 36 HD patients (median age 26 years). We excluded 10 patients with sexual
      inactivity in the past 4 weeks. Six of 37 men with ARM (16%) reported moderate to
      severe erectile dysfunction, vs. two of 18 men with HD (11%). Thirteen and 10 of
      26 women with ARM (50% and 38%) reported sexual dysfunction or sexual distress,
      respectively, vs. eight and three of 15 women with HD (53% and 20%). Quality of
      life and type of malformation or operation were not associated with self-reported
      psychosexual problems. Addressing sexuality with special interest to the
      congenital anomaly during medical care was reported to be insufficient by 42 ARM
      (60%) and 22 HD patients (61%). CONCLUSION: Approximately 13% of male ARM and HD
      patients reported erectile dysfunction, while 50% female ARM and HD patients
      reported sexual dysfunction not related to quality of life or type of
      malformation. Both ARM and HD patients felt a need for better addressing sexual
      concerns during medical care. Further research is needed to optimize form and
      timing of this education.

PMID- 25855235
TI  - Neonatal Overfeeding in Female Mice Predisposes the Development of Obesity in
      their Male Offspring via Altered Central Leptin Signalling.
AB  - The prevalence of obesity among child-bearing women has increased significantly.
      The adverse consequences of maternal obesity on the descendants have been well
      accepted, although few studies have examined the underlying mechanisms. We
      investigated whether neonatal overfeeding in female mice alters metabolic
      phenotypes in the offspring and whether hypothalamic leptin signalling is
      involved. Neonatal overfeeding was induced by reducing the litter size to three
      pups per litter, in contrast to normal litter size of 10 pups per litter. Normal
      and neonatally overfed female mice were bred with normal male mice, and offspring
      of overfeeding mothers (OOM) and control mothers (OCM) were generated. We
      examined body weight, daily food intake, leptin responsiveness and the number of
      positive neurones for phosphorylated-signal transducer and activator of
      transcription 3 (pSTAT3) along with neuropeptide Y (NPY) in the arcuate nucleus
      of the hypothalamus (ARH) and NPY in the nucleus tractus solitarius (NTS) of the
      brain stem. The body weight and daily food intake of OOM were significantly
      higher than those of OCM. Leptin significantly reduced food intake and increased
      the number of pSTAT3 positive neurones in the ARH of OCM mice, whereas no
      significant changes in food intake and pSTAT3 neurones were found in leptin
      treated OOM mice. The number of NPY neurones in the ARH and NTS of the OOM mice
      was significantly higher than that of OCM mice. The results of the present study
      indicate that the obese phenotype from mothers can be passed onto the subsequent
      generation, which is possibly associated with hypothalamic leptin resistance. 

PMID- 25855236
TI  - Molecular Cloning and Differential Expression of Cytosolic Class I Small Hsp Gene
      Family in Pennisetum glaucum (L.).
AB  - Small heat shock protein (Hsp) family genes have been reported in several plant
      species that function as molecular chaperones to protect proteins from being
      denatured in extreme conditions. As a first step towards the isolation and
      characterization of genes that contribute to combating abiotic stresses
      particularly heat stress, construction and screening of the subtracted
      complementary DNA (cDNA) library is reported here. In this study, a subtractive
      heat stress cDNA library was constructed that was used to isolate members of
      small Hsps (sHsps) using PgsHsp17.9A gene as a probe. As a result, a total of 150
      cDNA clones were isolated from the subtracted cDNA library screening, leading to
      121 high-quality expressed sequence tags (ESTs), with an average size of 450 bp,
      comprising of 15 contigs, and majority of these isolated sHsp genes belong to
      cytosolic class I (CI) family. In silico sequence analysis of CI-sHsp family
      genes revealed that the length of sHsp proteins varied from 151 to 159 amino
      acids and showed large variation in isoelectric point value (5.03 to 10.05) and a
      narrow range of molecular weight (16.09 to 17.94 kDa). The real-time PCR results
      demonstrated that CI-sHsp genes are differentially expressed in Pennisetum leaves
      under different abiotic stress conditions particularly at high temperature. The
      results presented in this study provide basic information on PgCI-sHsp family
      genes and form the foundation for future functional studies of these genes.

PMID- 25855238
TI  - Biodegradation of acetochlor by a newly isolated Pseudomonas strain.
AB  - A novel microbial strain JD115 capable of degrading acetochlor was isolated from
      the sludge of acetochlor manufacture and was identified as Pseudomonas aeruginosa
      species. This strain was able to grow on acetochlor as the sole source of both
      carbon and nitrogen. The biodegradation of acetochlor by strain JD115 could be
      described either by the pseudo-first-order or by the second-order kinetics
      models, while the latter gave a better performance. The strain optimally degraded
      acetochlor at a pH value of 7.0 and a temperature of 37  degrees C. Additional
      nutriments could greatly enhance the degradation rate of acetochlor up to 95.4%
      in the presence of 50 mg acetochlor l(-1). The metabolite analyses by GC-MS
      presumed that catechol was an intermediate product of acetochlor, which was
      finally degraded for 5 days of incubation. This study highlights the potential
      use of this strain for the bioremediation of an acetochlor-polluted environment.

PMID- 25855237
TI  - Expression of Rice Mature Carbonic Anhydrase Gene Increase E. coli Tolerance to
      Heat Stress.
AB  - Carbonic anhydrate is a zinc-containing metalloenzyme and involved in plant
      abiotic stress tolerance. In this study, we found that heat stress could induce
      rice mature carbonic anhydrate gene over-expression in rice plants. An
      Escherichia coli heterologous expression system was performed to identify the
      function of rice mature carbonic anhydrate in vitro. By sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE), mature OsCA fusion protein was
      identified and proved to be soluble. The results of spot, survival rate, and
      growth curve assay demonstrated that the expression of the mature OsCA could
      enhance the thermo-tolerance of the induced mature OsCA recombinants in
      comparison with controls under heat stress. Meanwhile, compared with controls,
      the levels of reactive oxygen species in induced mature OsCA recombinants were
      apparently low under heat stress, and correspondingly, activities of the critical
      antioxidant enzymes including superoxide dismutase, catalase, and peroxidase in
      the induced mature OsCA recombinants were significantly increased. Additionally,
      relative to controls, the activity of the lactate dehydrogenase decreased in the
      induced mature OsCA recombinants under heat stress. Based on these results, we
      suggest that mature OsCA protein could confer the E. coli recombinants' tolerance
      to heat stress by a synergistic fashion of increasing the antioxidant enzymes'
      activities to reduce the oxidative damage and maintaining the lactate
      dehydrogenase (LDH) activity of E. coli. 

PMID- 25855233
TI  - Developing Global Leaders for Research, Regulation, and Stewardship of Crop
      Protection Chemistry in the 21st Century.
AB  - To provide sufficient food and fiber to the increasing global population, the
      technologies associated with crop protection are growing ever more sophisticated
      but, at the same time, societal expectations for the safe use of crop protection
      chemistry tools are also increasing. The goal of this perspective is to highlight
      the key issues that face future leaders in crop protection, based on
      presentations made during a symposium titled "Developing Global Leaders for
      Research, Regulation and Stewardship of Crop Protection Chemistry in the 21st
      Century", held in conjunction with the IUPAC 13th International Congress of
      Pesticide Chemistry in San Francisco, CA, USA, during August 2014. The
      presentations highlighted the fact that leaders in crop protection must have a
      good basic scientific training and understand new and evolving technologies, are
      aware of the needs of both developed and developing countries, and have good
      communication skills. Concern is expressed over the apparent lack of resources to
      meet these needs, and ideas are put forward to remedy these deficiencies. 

PMID- 25855239
TI  - Removal of broken catheter piece with snare device during endovascular treatment
      of post-traumatic brachial artery pseudo-aneurysm.
AB  - Post-traumatic pseudo-aneurysm is a rare complication of penetrating vascular
      injury. Endovascular stent implantation has become an alternative approach in the
      management of this pathology. In our case, we present a brachial artery pseudo
      aneurysm that was treated with endovascular stent implantation, and removal of a
      broken catheter part with a three-dimensional snare device. 

PMID- 25855240
TI  - Tyrosine kinase inhibitors for epidermal growth factor receptor gene mutation
      positive non-small cell lung cancers: an update for recent advances in
      therapeutics.
AB  - The presence of activating gene mutations in the epidermal growth factor receptor
      of non-small cell lung cancer patients is predictive (improved progression-free
      survival and improved response rate) when treated with small molecule tyrosine
      kinase inhibitors such as gefitinib, erlotinib and afatinib. The two most common
      mutations that account for greater than 85% of all EGFR gene mutations are in
      frame deletions in exon 19 (LREA deletions) and substitution in exon 21 (L858R).
      Exon 18 mutations occur much less frequently at about 4% of all EGFR gene
      mutations. Together, exon 19 deletion and exon 21 L858R gene substitution are
      present in about 10% of Caucasian patients and 20-40% of Asian patients with non
      small cell lung cancer. T790M gene mutation at exon 20 is associated with
      acquired resistance to epidermal growth factor receptor tyrosine kinase
      inhibitors. Early studies showed that activating EGFR gene mutations are most
      common in patients with adenocarcinoma histology, women, never smokers and those
      of Asian ethnicity. A recent multi-center phase III trial suggested that
      frontline epidermal growth factor receptor tyrosine kinase inhibitor therapy with
      afatinib is associated with improved progression-free survival compared to
      chemotherapy regardless of race. Moreover, guidelines now suggest EGFR gene
      mutation testing should be conducted in all patients with lung adenocarcinoma or
      mixed lung cancers with an adenocarcinoma component, regardless of
      characteristics such as smoking status, gender or race. The success of targeted
      therapies in non-small cell lung cancer patients has changed the treatment
      paradigm in metastatic non-small cell lung cancer. However, despite a durable
      response of greater than a year, resistance to epidermal growth factor receptor
      tyrosine kinase inhibitors inevitably occurs. This mini-review describes the
      clinically relevant EGFR gene mutations and the efficacy/toxicity of small
      molecule epidermal growth factor receptor tyrosine kinase inhibitors as targeted
      therapies for these gene mutations. Therapeutic strategies to overcome
      resistance, including emerging and novel therapies, are discussed. 

PMID- 25855241
TI  - Bleomycin-induced flagellate erythema in a patient with Hodgkin's lymphoma - A
      case report and review of literature.
AB  - Bleomycin is a glycopeptide used as a chemotherapeutic agent for lymphomas, germ
      cell tumors, and pleurodesis of malignant pleural effusions. The pulmonary
      toxicity of bleomycin is well known while the cutaneous side effects are uncommon
      and varies from generalized hyperpigmentation, sclerodermoid changes, erythema
      multiformae, and gangrene to flagellate dermatosis. Here we report a
      characteristic but rare side effect of flagellate erythema, which developed
      secondary to bleomycin in a 27-year old woman with Hodgkin's lymphoma after two
      cycles of treatment with adriamycin, bleomycin, vinblastine, dacarbazine regimen.
      The rash subsided after discontinuation of bleomycin and treatment with steroids.

PMID- 25855242
TI  - Deep sequencing reveals the complete genome and evidence for transcriptional
      activity of the first virus-like sequences identified in Aristotelia chilensis
      (Maqui Berry).
AB  - Here, we report the genome sequence and evidence for transcriptional activity of
      a virus-like element in the native Chilean berry tree Aristotelia chilensis. We
      propose to name the endogenous sequence as Aristotelia chilensis Virus 1 (AcV1).
      High-throughput sequencing of the genome of this tree uncovered an endogenous
      viral element, with a size of 7122 bp, corresponding to the complete genome of
      AcV1. Its sequence contains three open reading frames (ORFs): ORFs 1 and 2 shares
      66%-73% amino acid similarity with members of the Caulimoviridae virus family,
      especially the Petunia vein clearing virus (PVCV), Petuvirus genus. ORF1 encodes
      a movement protein (MP); ORF2 a Reverse Transcriptase (RT) and a Ribonuclease H
      (RNase H) domain; and ORF3 showed no amino acid sequence similarity with any
      other known virus proteins. Analogous to other known endogenous pararetrovirus
      sequences (EPRVs), AcV1 is integrated in the genome of Maqui Berry and showed low
      viral transcriptional activity, which was detected by deep sequencing technology
      (DNA and RNA-seq). Phylogenetic analysis of AcV1 and other pararetroviruses
      revealed a closer resemblance with Petuvirus. Overall, our data suggests that
      AcV1 could be a new member of Caulimoviridae family, genus Petuvirus, and the
      first evidence of this kind of virus in a fruit plant.

PMID- 25855245
TI  - Case of Sjogren-Larsson syndrome with a large deletion in the ALDH3A2 gene
      confirmed by single nucleotide polymorphism array analysis.
AB  - Sjogren-Larsson syndrome (SLS) is a neurocutaneous disorder inherited in an
      autosomal recessive fashion. SLS patients are characterized by lipid metabolism
      error, primarily leading to cardinal signs of ichthyosis, spasticity and mental
      retardation. Additional signs include short stature, epilepsy, retinal
      abnormalities and photophobia. More than 90 mutations of the ALDH3A2 gene have
      been reported for SLS, and such variants can be successfully detected at a rate
      of 94% by direct DNA sequencing. We performed direct sequencing of ALDH3A2 gene
      from the index patient, however, no mutation could be detected. HumanCytoSNPs12
      array analysis and subsequent targeted single nucleotide polymorphism analysis
      revealed a novel deletion mutation at chromosome 17p11.2. This 67-Kb region
      includes the first five coding exons of ALDH3A2, and is flanked by rs2245639 and
      rs962801. To the best of our knowledge, this mutation is novel and our findings
      broaden the mutation spectrum of ALDH3A2 causing SLS phenotype. 

PMID- 25855244
TI  - A Synopsis of Clinical Pharmacokinetic Alterations in Advanced CKD.
AB  - Unrecognized alterations in pharmacokinetics, which quantitatively describes the
      time course of drug disposition in the body, may lead to clinically significant
      changes in systemic exposure and corresponding response to drugs in patients with
      chronic kidney disease (CKD). Clinicians must take pharmacokinetic changes into
      consideration when selecting and dosing medications in CKD patients to optimize
      the risk:benefit ratio. Pharmacokinetic changes in absorption, distribution, and
      renal clearance are well characterized and generally predictable for most drugs.
      Conversely, changes in nonrenal clearance are less well understood and
      corresponding clinical implications are still being elucidated. This review
      provides a synopsis of alterations in each of these pharmacokinetic parameters
      observed in patients with advanced CKD. 

PMID- 25855243
TI  - Incorporation of spike and membrane glycoproteins into coronavirus virions.
AB  - The envelopes of coronaviruses (CoVs) contain primarily three proteins; the two
      major glycoproteins spike (S) and membrane (M), and envelope (E), a non
      glycosylated protein. Unlike other enveloped viruses, CoVs bud and assemble at
      the endoplasmic reticulum (ER)-Golgi intermediate compartment (ERGIC). For
      efficient virion assembly, these proteins must be targeted to the budding site
      and to interact with each other or the ribonucleoprotein. Thus, the efficient
      incorporation of viral envelope proteins into CoV virions depends on protein
      trafficking and protein-protein interactions near the ERGIC. The goal of this
      review is to summarize recent findings on the mechanism of incorporation of the M
      and S glycoproteins into the CoV virion, focusing on protein trafficking and
      protein-protein interactions. 

PMID- 25855246
TI  - Lateralizing value of semiology in medial temporal lobe epilepsy.
AB  - OBJECTIVES: Analysing the clinical characteristics of seizures constitutes a
      fundamental aspect of the presurgical evaluation of patients with medial temporal
      lobe epilepsy and unilateral hippocampal sclerosis (MTLE-HS), the most frequent
      form of focal epilepsy accessible to surgery. We sought to retrospectively
      determine whether objective manifestations could have a reliable lateralizing
      value in a large population of MTLE-HS patients and if their presence could help
      to identify those patients who would be seizure free after surgery. MATERIAL AND
      METHODS: We analysed the frequency and predictive lateralizing value of objective
      ictal and postictal signs in 391 patients with MTLE-HS (183 left/208 right). Data
      were derived from chart review and not from blinded videoEEG analysis.
      Correlation between the presence of reliable lateralizing signs and postoperative
      outcome was performed in a subgroup of 302 patients who underwent surgery.
      RESULTS: Contralateral dystonic posturing was the most frequent and reliable
      lateralizing sign that correctly lateralized the focus in 96% of patients.
      Unilateral head/eye deviation was noted in 42% of the patients and predicted
      unilateral focus in 67%. Ipsilateral postictal nose wiping, contralateral clonus
      and hypokinesia correctly lateralized the focus in 75%, 81%, respectively, and
      100 of patients but were less frequently depicted. Postictal aphasia was a strong
      lateralizing sign for left MLE-HS. The presence of reliable lateralizing signs
      was not a predictor of seizure freedom. CONCLUSION: Seizure semiology is a simple
      tool that may permit reliable lateralization of the seizure focus in MTLE-HS. The
      presence of reliable lateralizing signs is not associated with a better
      postoperative outcome.

PMID- 25855247
TI  - Barriers to exercise prescription and participation in people with mental
      illness: the perspectives of nurses working in mental health.
AB  - ACCESSIBLE SUMMARY: Exercise is valuable in the treatment of mental illness, yet
      personal and organizational barriers limit widespread implementation by nurses in
      mental health settings. Using a self-report questionnaire, we sought to identify
      how often nurses prescribe exercise and their level of agreement with previously
      identified barriers to exercise prescription and participation for mental health
      consumers. Nurses disagree that many of the previously identified barriers should
      impede exercise prescription for people with mental illness. Nurses agree that
      many of the barriers expressed by mental health consumers might prevent exercise
      participation. Our study provides valuable new insight into the role of nurses in
      the provision of exercise for people with mental illness; however, it is limited
      to a small sample. Confirmation of these findings in larger, geographically and
      professionally diverse groups is needed. ABSTRACT: Evidence is mounting for the
      efficacy of exercise in the treatment of people with mental illness. Nurses
      working in mental health settings are well placed to provide exercise advice for
      people with mental illness. However, quantitative examinations of the barriers to
      exercise prescription experienced by nurses, or their views regarding the
      barriers to exercise participation experienced by people with mental illness, are
      lacking. In this study, 34 nurses completed the Exercise in Mental Illness
      Questionnaire-Health Professionals Version (EMIQ-HP). This survey examined the
      frequency of exercise prescription and the level of agreement with statements
      regarding barriers to exercise prescription for, and exercise participation by,
      people with mental illness. The level of agreement scores for statements for each
      section was summed, with a higher score indicating a higher level of agreement.
      Nurses disagree with many of the barriers to exercise prescription presented in
      the literature. The level of agreement scores did not differ between nurses who
      prescribe exercise 'Always', 'Most of the time', 'Occasionally' or 'Never'. We
      found a non-significant negative relationship between frequency of exercise
      prescription and summed level of agreement scores for barriers to exercise
      prescription. Consensus regarding barriers to exercise participation by mental
      health consumers is less clear. This study provides valuable new insight into the
      role of nurses in the provision of exercise for people with mental illness.
      Confirmation in larger samples is needed before translation of research to
      practice.

PMID- 25855248
TI  - Reduced skeletal muscle oxidative capacity and impaired training adaptations in
      heart failure.
AB  - Systolic heart failure (HF) is associated with exercise intolerance that has been
      attributed, in part, to skeletal muscle dysfunction. The purpose of this study
      was to compare skeletal muscle oxidative capacity and training-induced changes in
      oxidative capacity in participants with and without HF. Participants with HF (n =
      16, 65 +/- 6.6 years) were compared with control participants without HF (n = 23,
      61 +/- 5.0 years). A subset of participants (HF: n = 7, controls: n = 5)
      performed 4 weeks of wrist-flexor exercise training. Skeletal muscle oxidative
      capacity was determined from the recovery kinetics of muscle oxygen consumption
      measured by near-infrared spectroscopy (NIRS) following a brief bout of wrist
      flexor exercise. Oxidative capacity, prior to exercise training, was
      significantly lower in the HF participants in both the dominant (1.31 +/- 0.30
      min(-1) vs. 1.59 +/- 0.25 min(-1), P = 0.002; HF and control groups,
      respectively) and nondominant arms (1.29 +/- 0.24 min(-1) vs. 1.46 +/- 0.23 min(
      1), P = 0.04; HF and control groups, respectively). Following 4 weeks of
      endurance training, there was a significant difference in the training response
      between HF and controls, as the difference in oxidative training adaptations was
      0.69 +/- 0.12 min(-1) (P < 0.001, 95% CI 0.43, 0.96). The wrist-flexor training
      induced a ~50% improvement in oxidative capacity in participants without HF (mean
      difference from baseline = 0.66 +/- 0.09 min(-1), P < 0.001, 95% CI 0.33, 0.98),
      whereas participants with HF showed no improvement in oxidative capacity (mean
      difference from baseline = -0.04 +/- 0.08 min(-1), P = 0.66, 95% CI -0.24, 0.31),
      suggesting impairments in mitochondrial biogenesis. In conclusion, participants
      with HF had reduced oxidative capacity and impaired oxidative adaptations to
      endurance exercise compared to controls. 

PMID- 25855249
TI  - Subcortical orientation biases explain orientation selectivity of visual cortical
      cells.
AB  - The primary visual cortex of carnivores and primates shows an orderly progression
      of domains of neurons that are selective to a particular orientation of visual
      stimuli such as bars and gratings. We recorded from single-thalamic afferent
      fibers that terminate in these domains to address the issue whether the
      orientation sensitivity of these fibers could form the basis of the remarkable
      orientation selectivity exhibited by most cortical cells. We first performed
      optical imaging of intrinsic signals to obtain a map of orientation domains on
      the dorsal aspect of the anaesthetized cat's area 17. After confirming using
      electrophysiological recordings the orientation preferences of single neurons
      within one or two domains in each animal, we pharmacologically silenced the
      cortex to leave only the afferent terminals active. The inactivation of cortical
      neurons was achieved by the superfusion of either kainic acid or muscimol.
      Responses of single geniculate afferents were then recorded by the use of high
      impedance electrodes. We found that the orientation preferences of the afferents
      matched closely with those of the cells in the orientation domains that they
      terminated in (Pearson's r = 0.633, n = 22, P = 0.002). This suggests a possible
      subcortical origin for cortical orientation selectivity. 

PMID- 25855250
TI  - Missing gold atoms in lysozyme crystals used to grow gold nanoparticles.

PMID- 25855251
TI  - Pre-market testing of nanomaterials in food is both practical and necessary.

PMID- 25855252
TI  - Nanomaterials in art conservation.

PMID- 25855253
TI  - Thank you, Royal Society.

PMID- 25855255
TI  - Gut immunology: Nanoparticles ferry gut antigens.

PMID- 25855256
TI  - Cancer nanomedicine: Therapy from within.

PMID- 25855257
TI  - Correction.

PMID- 25855258
TI  - From nano to micro and back.

PMID- 25855259
TI  - A phase-II sequential case-series study of all patients presenting to four plasma
      exchange centres with presumed relapsed/refractory thrombotic thrombocytopenic
      purpura treated with rituximab.
AB  - The primary objective of this phase II study was to evaluate the efficacy of
      rituximab in the management of adult patients with physician-diagnosed presumed
      thrombotic thrombocytopenic purpura (TTP); relapsed or refractory. We conducted a
      multicentre study in four Canadian hospital-based apheresis units. Forty patients
      with presumed TTP (20 refractory and 20 relapsing) were sequentially enrolled and
      all received rituximab in a standardized manner. A complete response was
      documented in 14 of 19 refractory patients by week 8 and 15/16 were alive and in
      remission at 52 weeks (one patient was lost to follow-up, one was a non
      responder, and three died). Among relapsing patients, 16/18 had a complete
      response at week 8 and 18/18 at week 52 (one patient lost to follow-up and one
      withdrew). At 1 year, all relapsing and 85% of refractory patients survived. Of
      38/40 patients who had ADMATS13 testing at study entry, 13/19 refractory and
      10/19 relapsing patients had ADAMTS13 < 10% (typical TTP); whereas 6/19
      refractory and 9/19 relapsing cases had ADAMTS13 > 10% (other thrombotic
      microangiopathy; TMA). Refractory-typical TTP in contrast to refractory-other TMA
      and all relapsing patients treated with plasma exchange and rituximab, were less
      likely to be responsive and more likely to die or relapse. 

PMID- 25855260
TI  - Quenching of the electrochemiluminescence of RU-complex tagged shared-stem
      hairpin probes by graphene oxide and its application to quantitative turn-on
      detection of DNA.
AB  - Efficient and stable quenching of electrochemiluminescence (ECL) of tris(2,2'
      bipyridine)-ruthenium(II) (Ru(bpy)3(2+))/tri-n-propylamine (TPrA) system by
      graphene oxide (GO) at the glassy carbon electrode (GCE) was reported. For
      figuring out the possible reasons of the quenching mechanism, the electrochemical
      and ECL performance of GO, different reduction degree of reduced graphene oxide
      (RGOs) and polymer wrapped GO modified GCEs were systematacially investigated.
      The results demonstrated that the oxygen-containing groups and poor electrical
      conductivity of GO, along with the distance between GO and Ru(bpy)3(2+) was
      suggested as the reasons for quenching ECL. On the basis of this essential
      quenching mechanism, a novel "signal on" ECL DNA biosensor for ultrasensitive
      detection of specific DNA sequence was constructed by self-assembling the ECL
      probe of thiolated shared-stem hairpin DNA (SH-DNA) tagged with Ru complex
      (Ru(bpy)3(2+) derivatives) on the surface of GO/gold nanoparticles (AuNPs)
      modified GCE. The ECL probe sequences have their ECL signal efficiently quenched
      when they are self-assembled on the surface of GO unless they hybridizes with
      their target DNA (t-DNA) sequence. The designed ECL biosensor exhibited excellent
      stability and reproducibility, outstanding selectivity, and an extremely
      sensitive response to t-DNA in a wide linear range of 100 aM-10 pM with a low
      detection limit of 65 aM. Our findings and the design of biosensing switch would
      open a new avenue in the application of GO based ECL quenching strategy for
      ultrasensitive bioassays.

PMID- 25855262
TI  - Systemic morphine treatment derails normal uterine receptivity, leading to embryo
      implantation failure in mice.
AB  - Morphine is the oldest worldwide well-known opioid agonist used for pain
      treatment in clinic, and its illicit use is often associated with adverse
      pregnancy outcomes in humans. Because of recent dramatic increases in
      nonmedicinal morphine abuse, one emerging issue is the further revelation of the
      dark side of illicit opioid uses, particularly in early pregnancy events. In this
      respect, we have demonstrated that opioid signaling is functionally operative
      during preimplantation embryo development in mice. However, the
      pathophysiological significance of the opioid system on uterine functions at peri
      implantation remained elusive. In the present study, we demonstrated that opioid
      receptors were spatiotemporally expressed in the uterus during the peri
      implantation period. Employing a pharmacological approach combined with embryo
      transfer experiments, we further observed that although systemic morphine
      treatment exerts no apparent adverse influence on preimplantation ovarian
      secretion of progesterone and estrogen, this aberrant activation of opioid
      signaling by morphine induces impaired luminal epithelial differentiation,
      decreased stromal cell proliferation, and poor angiogenesis, and thus hampers
      uterine receptivity and embryo implantation. These novel findings add a new line
      of evidence to better understand the causes for obvious adverse effects of opioid
      abuse on pregnancy success in women. 

PMID- 25855261
TI  - Flow cytometry analysis reveals that only a subpopulation of mouse sperm
      undergoes hyperpolarization during capacitation.
AB  - To gain fertilizing capacity, mammalian sperm should reside in the female tract
      for a period of time. The physiological changes that render the sperm able to
      fertilize are known as capacitation. Capacitation is associated with an increase
      in intracellular pH, an increase in intracellular calcium, and phosphorylation of
      different proteins. This process is also accompanied by the hyperpolarization of
      the sperm plasma membrane potential (Em). In the present work, we used flow
      cytometry to analyze changes in sperm Em during capacitation in individual cells.
      Our results indicate that a subpopulation of hyperpolarized mouse sperm can be
      clearly distinguished by sperm flow cytometry analysis. Using sperm bearing green
      fluorescent protein in their acrosomes, we found that this hyperpolarized
      subpopulation is composed of sperm with intact acrosomes. In addition, we show
      that the capacitation-associated hyperpolarization is blocked by high
      extracellular K(+), by PKA inhibitors, and by SLO3 inhibitors in CD1 mouse sperm,
      and undetectable in Slo3 knockout mouse sperm. On the other hand, in sperm
      incubated in conditions that do not support capacitation, sperm membrane
      hyperpolarization can be induced by amiloride, high extracellular NaHCO3, and
      cAMP agonists. Altogether, our observations are consistent with a model in which
      sperm Em hyperpolarization is downstream of a cAMP-dependent pathway and is
      mediated by the activation of SLO3 K(+) channels. 

PMID- 25855264
TI  - Purification and Transcriptomic Analysis of Mouse Fetal Leydig Cells Reveals
      Candidate Genes for Specification of Gonadal Steroidogenic Cells.
AB  - Male sex determination hinges on the development of testes in the embryo,
      beginning with the differentiation of Sertoli cells under the influence of the Y
      linked gene SRY. Sertoli cells then orchestrate fetal testis formation including
      the specification of fetal Leydig cells (FLCs) that produce steroid hormones to
      direct virilization of the XY embryo. As the majority of XY disorders of sex
      development (DSDs) remain unexplained at the molecular genetic level, we reasoned
      that genes involved in FLC development might represent an unappreciated source of
      candidate XY DSD genes. To identify these genes, and to gain a more detailed
      understanding of the regulatory networks underpinning the specification and
      differentiation of the FLC population, we developed methods for isolating fetal
      Sertoli, Leydig, and interstitial cell-enriched subpopulations using an Sf1-eGFP
      transgenic mouse line. RNA sequencing followed by rigorous bioinformatic
      filtering identified 84 genes upregulated in FLCs, 704 genes upregulated in
      nonsteroidogenic interstitial cells, and 1217 genes upregulated in the Sertoli
      cells at 12.5 days postcoitum. The analysis revealed a trend for expression of
      components of neuroactive ligand interactions in FLCs and Sertoli cells and
      identified factors potentially involved in signaling between the Sertoli cells,
      FLCs, and interstitial cells. We identified 61 genes that were not known
      previously to be involved in specification or differentiation of FLCs. This
      dataset provides a platform for exploring the biology of FLCs and understanding
      the role of these cells in testicular development. In addition, it provides a
      basis for targeted studies designed to identify causes of idiopathic XY DSD. 

PMID- 25855263
TI  - The Potential Role of Amh to Prevent Ectopic Female Development in Testicular
      Tissue of the Protandrous Black Porgy, Acanthopagrus schlegelii.
AB  - In most vertebrates, hermaphroditism results in infertility. However,
      hermaphroditism occurs in 6% of teleosts, which primarily undergo protogyny.
      Here, to elucidate the transient stage from gonochorism to hermaphroditism,
      juvenile black porgies as a model animal were fed a diet containing estradiol
      (E2) for 3 mo, followed by withdrawal of E2 treatment. The E2-terminated fish had
      ectopically located oocytes in the regenerated testes. Antimullerian hormone
      (amh) was strongly expressed in the Sertoli cells with type A spermatogonia and
      follicle cells with vitellogenic oocytes. Amh was robustly expressed in the
      ectopic oocytes-bordering region of regenerated testes and in testes with
      nonsynchronous spermatogenesis. This Amh was released by Sertoli cells and
      aggregated in the area containing type A spermatogonia in the ectopic oocytes
      bordering region. Our in vitro results show that exogenous recombinant Amh (rAmh)
      can inhibit type A spermatogonia proliferation in the testis but not oogonia
      proliferation in the ovary. We suggest that Amh-arrested spermatogonia A may act
      as a boundary to block intercellular communication (i.e., prevent peptide factors
      released from female tissue to alter the sexual fate of type A spermatogonia) and
      further inhibit female growth. These results suggest that black porgy can prevent
      ectopic female growth in the testis and maintain male function of the digonic
      gonad (testes and ovary separated by the connective tissue) through Amh action.
      This function of amh might shed light on why the majority of syngonic fish
      undergo protogyny (female-to-male sex change). 

PMID- 25855265
TI  - The role of chemisorbed hydroxyl species in alkaline electrocatalysis of glycerol
      on gold.
AB  - The mechanism of energy conversion in a direct glycerol fuel cell (DGFC) is
      governed by the anode supported heterogeneous steps of glycerol electro
      oxidation. In aerated alkaline electrolytes, glycerol also participates in a base
      catalyzed process, which can release certain species mixing with the anode
      catalyzed surface products. As a result, selective probing of the surface
      catalytic reactions involving such systems can be difficult. The present work
      addresses this issue for a gold anode by using the analytical capability of
      cyclic voltammetry (CV). In addition, surface plasmon resonance measurements are
      used to optically probe the adsorption characteristics of the electrolyte
      species. The net exchange current of the oxidation process and the transfer
      coefficient of the rate determining step are evaluated by analyzing the CV data.
      The interfacial reactions and their products on Au are identified by measuring
      the number of electrons released during the electro-oxidation of glycerol. The
      results indicate that these reactions are facilitated by the surface bound
      hydroxyl species on Au (chemisorbed OH(-) and faradaically formed Au-OH). By
      comparing the findings for stationary and rotating electrodes, it is shown that,
      convective mass transport is critical to maintaining efficient progression of the
      consecutive oxidation steps of glycerol. In the absence of hydrodynamic support,
      the main surface products of glycerol oxidation appear to be glyceraldehyde,
      glycerate and malonate, formed through a net six-electron route. In the presence
      of controlled convection, a ten-electron process is activated, where mesaxolate
      is the likely additional product. 

PMID- 25855266
TI  - Descriptive study on neural tube defects in Argentina.
AB  - BACKGROUND: Neural tube defects (NTDs) are the most common congenital anomalies
      of the central nervous system. Prevalence of NTDs varies depending on geographic
      region and folic acid fortification. The main objectives of this study are to
      analyze the prevalences of NTDs reported to the National Registry of Congenital
      Anomalies of Argentina (RENAC) during the period 2009 to 2013, to compare them
      with data from other selected surveillance systems of the Americas, and to
      evaluate the impact of folic acid fortification on the prevalence of NTDs in
      Argentina. METHODS: We analyzed changes in prevalence between 2009 and 2013 for
      the RENAC, and differences in prevalence between RENAC and other surveillance
      systems. We evaluated changes for the pre and postfortification time periods in
      Argentina. RESULTS: In Argentina, anencephaly and spina bifida showed no
      statistically significant variation between 2009 and 2013, and encephalocele
      showed a statistically significant decline. The RENAC showed a statistically
      significant higher prevalence for all three defects when compared with
      surveillance systems from Chile, Colombia, and Costa Rica, and a statistically
      significant lower birth prevalence than Cuba for anencephaly. No differences were
      observed when comparing it to the Atlanta-USA and Mexico systems. A significant
      decrease in prevalence was observed for all three anomalies for the
      postfortification period in Argentina. CONCLUSION: The characteristics of cases
      reported to the RENAC are similar to those already reported in the literature.
      The differences in prevalence between the RENAC and other surveillance systems
      could be artifactual or real. We confirmed the decrease of prevalence of NTDs
      after folic acid fortification.

PMID- 25855268
TI  - Copper-catalyzed tandem phosphination-decarboxylation-oxidation of alkynyl acids
      with H-phosphine oxides: a facile synthesis of beta-ketophosphine oxides.
AB  - The general method for the tandem phosphination-decarboxylation-oxidation of
      alkynyl acids under aerobic conditions has been developed. In the presence of
      CuSO4.5H2O and TBHP, the reactions provide a novel access to beta-ketophosphine
      oxides in good to excellent yields. This transformation allows the direct
      formation of a P-C bond and the construction of a keto group in one reaction. 

PMID- 25855267
TI  - Comparison of the pharmacokinetics of an oral extended-release capsule
      formulation of carbidopa-levodopa (IPX066) with immediate-release carbidopa
      levodopa (Sinemet((r))), sustained-release carbidopa-levodopa (Sinemet((r)) CR),
      and carbidopa-levodopa-entacapone (Stalevo((r))).
AB  - IPX066 (extended-release carbidopa-levodopa [ER CD-LD]) is an oral extended
      release capsule formulation of carbidopa and levodopa. The single-dose
      pharmacokinetics of ER CD-LD (as 2 capsules; total dose, 97.5 mg-390 mg CD-LD)
      versus immediate-release (IR) CD-LD (25 mg-100 mg), sustained-release (CR) CD-LD
      (25 mg-100 mg), and CD-LD-entacapone (25 mg-100 mg-200 mg) was evaluated in
      healthy subjects. Following IR dosing, LD reached peak concentrations (Cmax ) at
      1 hour; LD concentrations then decreased rapidly and were less than 10% of peak
      by 5 hours. With CR CD-LD and CD-LD-entacapone, LD Cmax occurred at 1.5 hours,
      and concentrations were less than 10% of peak by 6.3 and 7.5 hours, respectively.
      The initial increase in LD concentration was similar between ER CD-LD and IR CD
      LD and faster than for CR CD-LD and CD-LD-entacapone. LD concentrations from ER
      CD---LD were sustained for approximately 5 hours and did not decrease to 10% of
      peak until 10.1 hours. Dose-normalized LD Cmax values for ER CD-LD were
      significantly lower (P< .05) than for the other CD-LD products. Bioavailability
      of LD from ER CD-LD was 83.5%, 78.3%, and 58.8% relative to IR CD-LD, CR CD-LD,
      and CD-LD-entacapone, respectively. 

PMID- 25855269
TI  - [Modern neurosciences: with or without optogenetics?].

PMID- 25855270
TI  - [Random fluctuations, metabolism and growth at the single-cell level].

PMID- 25855271
TI  - [The European Blueprint project: towards a full epigenome characterization of the
      immune system].

PMID- 25855272
TI  - [Hair keratins in tooth enamel: the link between hair disorders and dental
      caries].

PMID- 25855273
TI  - [Treatment of alveolar proteinosis by intrapulmonary transplantation of
      macrophages].

PMID- 25855274
TI  - [A new oncogenic switch in prostate cancer progression: the exceptional ORAI3].

PMID- 25855275
TI  - [High-throughput small interfering RNA screens: when small interfering RNAs
      behave like microRNA].

PMID- 25855276
TI  - [Centriole amplification ? #DaughterCentriole].

PMID- 25855277
TI  - [Functional correction and cognitive improvement in dystrophic mice using splice
      switching tricyclo-DNA oligomers].

PMID- 25855278
TI  - [Transplantation of iPS-derived hepatocytes into a mouse liver: a new murine
      model of hepatitis C virus infection].

PMID- 25855279
TI  - [In the heart of noncoding RNA: a long way to go].
AB  - The identification and characterization of long noncoding RNA in a variety of
      tissues represent major achievements that contribute to our understanding of the
      molecular mechanisms controlling gene expression. In particular, long noncoding
      RNA play crucial roles in the epigenetic regulation of the adaptive response to
      environmental cues via their capacity to target chromatin modifiers to specific
      locus. In addition, these transcripts have been implicated in controlling
      splicing, translation and degradation of messenger RNA. Long noncoding RNA have
      also been shown to act as decoy molecules for microRNA. In the heart, a few long
      noncoding RNA have been demonstrated to regulate cardiac commitment and
      differentiation during development. Furthermore, recent findings suggest their
      involvement as regulators of the pathophysiological response to injury in the
      adult heart. Their high cellular specificity makes them attractive target
      molecules for innovative therapies and ideal biomarkers. 

PMID- 25855280
TI  - [Properties and biological roles of TET proteins during embryogenesis and in
      hematopoiesis].
AB  - DNA methylation is associated with a large number of biological processes and
      mainly concerns the cytosine methylation at position 5 (5-mC). An active
      demethylation mechanism was highlighted in 2009 following the discovery that TET
      proteins were enzymes implicated in the hydroxylation of 5-mC to 5
      hydroxymethylcytosine. Simultaneously, other studies showed frequent acquired
      TET2 mutations in hematological malignancies and have depicted their role in
      their pathogenesis. An entire field of research has developed rapidly showing
      that these proteins are involved in many biological processes. 

PMID- 25855282
TI  - [Protein synthesis by the ribosome: a pathway full of pitfalls].
AB  - Protein synthesis is accomplished through a process known as translation and is
      carried out by the ribosome, a large macromolecular complex found in every living
      organism. Given the huge amount of biological data that must be deciphered, it is
      not uncommon for ribosomes to regularly stall during the process of translation.
      Any disruption of this finely tuned process will jeopardize the viability of the
      cell. In bacteria, the main quality-control mechanism for rescuing ribosomes that
      undergo arrest during translation is trans-translation, which is performed by
      transfer-messenger RNA (tmRNA) in association with small protein B (SmPB).
      However, other rescue systems have been discovered recently, revealing a far more
      complicated network of factors dedicated to ribosome rescue. These discoveries
      make it possible to consider inhibition of these pathways as a very promising
      target for the discovery of new antibiotics. 

PMID- 25855281
TI  - [The APJ receptor: a new therapeutic approach in diabetic treatment].
AB  - The APJ receptor cloned in 1993 found its ligand in 1998 with the discovery of
      apelin. The presence of APJ in the central nervous system (more particularly in
      the hypothalamus) and in various tissues (heart, blood vessels, stomach, etc.)
      makes it a potential pharmacological target. Interest in APJ has allowed the
      development of peptidic molecules able to stimulate and/or inhibit the receptor
      and, more recently, to discover another endogenous ligand: apela. Among the
      functions regulated by the APJ/apelin system, the control of energy metabolism
      appears today in the forefront. A better understanding of the pharmacology of APJ
      receptor should allow innovative therapeutic approaches in the treatment of
      metabolic diseases. 

PMID- 25855283
TI  - [Principles and applications of optogenetics in neuroscience].
AB  - Numerous achievements in biology have resulted from the evolution of
      biophotonics, a general term describing the use of light in the study of living
      systems. Over the last fifteen years, biophotonics has progressively blended with
      molecular genetics to give rise to optogenetics, a set of techniques enabling the
      functional study of genetically-defined cellular populations, compartments or
      processes with optical methods. In neuroscience, optogenetics allows real-time
      monitoring and control of the activity of specific neuronal populations in a wide
      range of animal models. This technical breakthrough provides a new level of
      sophistication in experimental approaches in the field of fundamental
      neuroscience, significantly enhancing our ability to understand the complexity of
      neuronal circuits. 

PMID- 25855284
TI  - [The intimate genome... in three dimensions].
AB  - Over the past decade, techniques based on chromosome conformation capture (3C)
      have accelerated our understanding of eukaryote's nuclear architecture. Coupled
      to high throughput sequencing and bioinformatics they have unveiled different
      organizational levels of the genome at an unprecedented scale. Initially
      performed using large populations of cells, a new variant of these techniques can
      be applied to single cell. Although it can be shown that chromosome folding
      varies from one cell to the other, their overall organization into topologically
      associating domains is conserved between cells of the same population.
      Interestingly, the predicted chromosome structures reveal that regions engaged in
      trans-chromosomal interactions are preferentially localized at the surface of the
      chromosome territory. These results confirm and extend previous observations on
      individual loci therefore highlighting the power of 3C based techniques. 

PMID- 25855285
TI  - [Chemical libraries dedicated to protein-protein interactions].
AB  - The identification of complete networks of protein-protein interactions (PPI)
      within a cell has contributed to major breakthroughs in understanding biological
      pathways, host-pathogen interactions and cancer development. As a consequence,
      PPI have emerged as a new class of promising therapeutic targets. However, they
      are still considered as a challenging class of targets for drug discovery
      programs. Recent successes have allowed the characterization of structural and
      physicochemical properties of protein-protein interfaces leading to a better
      understanding of how they can be disrupted with small molecule compounds. In
      addition, characterization of the profiles of PPI inhibitors has allowed the
      development of PPI-focused libraries. In this review, we present the current
      efforts at developing chemical libraries dedicated to these innovative targets. 

PMID- 25855286
TI  - [How independent pharmacological screenings in plants and humans led to the
      discovery of a new family of lipid metabolism inhibitors].
AB  - In eukaryotic cells, phosphatidic acid (PA) and diacylglycerol (DAG), are at the
      origin of all membrane glycerolipids. Their interconversion is achieved by
      dephosphorylation of PA and phosphorylation of DAG: they form therefore a
      metabolic hub. PA and DAG are also known to be versatile signaling molecules. Two
      independent pharmacological screenings conducted on plant and human targets, led
      to the discovery of a new family of compounds acting on enzymes binding to either
      PA or DAG, in biological contexts that seemed initially independent. On the one
      hand, in plants, monogalactosyldiacylglycerol synthases (MGDG synthases or MGD)
      are responsible for the synthesis of MGDG, which is the most profuse lipid of
      photosynthetic membranes, and thus essential for metabolism and development. MGD
      use DAG as substrate. On the other hand, in mammals, phospholipases D (PLD), that
      produce PA, are involved in a variety of signaling cascades that control a broad
      spectrum of cellular functions, and play a role in the development of cancers.
      The two independent pharmacological screenings described in this review aimed to
      identify inhibitory molecules of either MGD of the plant model Arabidopsis, or
      human PLD. In both cases, the obtained molecules are piperidinyl-benzimidazolone
      derivatives, thereby allowing to propose this family of molecules as a novel
      source of inspiration for the search of compounds interfering with glycerolipid
      metabolism, that could be useful for other biological and therapeutics contexts. 

PMID- 25855287
TI  - [Illnesses and diseases in history: usefulness of their study for contemporary
      medicine and public health].
AB  - History of illnesses and diseases contributes to the study of pathological
      phenomena, for it provides data on their dynamics, their emergence and spread,
      and their relationships with the physical and human environment. It also shed
      light on how states or conditions have been labeled as "diseases", and questions
      the universality of pathological categories used by medicine. Like cross-cultural
      studies, research on ancient medical writings allows to identify consistent as
      well as variable expressions of illnesses ; this may in turn allow to
      discriminate whether pathogenesis is based mainly on a biological nature or on a
      socio-cultural nature. We will describe case studies from the eighteenth-century
      in France to illustrate the usefulness of studying history of illnesses and
      diseases for contemporary medicine and public health. 

PMID- 25855288
TI  - [Proper use of non-invasive prenatal tests].

PMID- 25855289
TI  - A model of breast cancer heterogeneity reveals vascular mimicry as a driver of
      metastasis.
AB  - Cancer metastasis requires that primary tumour cells evolve the capacity to
      intravasate into the lymphatic system or vasculature, and extravasate into and
      colonize secondary sites. Others have demonstrated that individual cells within
      complex populations show heterogeneity in their capacity to form secondary
      lesions. Here we develop a polyclonal mouse model of breast tumour heterogeneity,
      and show that distinct clones within a mixed population display specialization,
      for example, dominating the primary tumour, contributing to metastatic
      populations, or showing tropism for entering the lymphatic or vasculature
      systems. We correlate these stable properties to distinct gene expression
      profiles. Those clones that efficiently enter the vasculature express two
      secreted proteins, Serpine2 and Slpi, which were necessary and sufficient to
      program these cells for vascular mimicry. Our data indicate that these proteins
      not only drive the formation of extravascular networks but also ensure their
      perfusion by acting as anticoagulants. We propose that vascular mimicry drives
      the ability of some breast tumour cells to contribute to distant metastases while
      simultaneously satisfying a critical need of the primary tumour to be fed by the
      vasculature. Enforced expression of SERPINE2 and SLPI in human breast cancer cell
      lines also programmed them for vascular mimicry, and SERPINE2 and SLPI were
      overexpressed preferentially in human patients that had lung-metastatic relapse.
      Thus, these two secreted proteins, and the phenotype they promote, may be broadly
      relevant as drivers of metastatic progression in human cancer. 

PMID- 25855290
TI  - Structural biology: Pain-sensing TRPA1 channel resolved.

PMID- 25855291
TI  - Ecology: Recovering the potential of coral reefs.

PMID- 25855292
TI  - Cancer: An extravascular route for tumour cells.

PMID- 25855293
TI  - Particle physics: A weighty mass difference.

PMID- 25855294
TI  - SHMT2 drives glioma cell survival in ischaemia but imposes a dependence on
      glycine clearance.
AB  - Cancer cells adapt their metabolic processes to support rapid proliferation, but
      less is known about how cancer cells alter metabolism to promote cell survival in
      a poorly vascularized tumour microenvironment. Here we identify a key role for
      serine and glycine metabolism in the survival of brain cancer cells within the
      ischaemic zones of gliomas. In human glioblastoma multiforme, mitochondrial
      serine hydroxymethyltransferase (SHMT2) and glycine decarboxylase (GLDC) are
      highly expressed in the pseudopalisading cells that surround necrotic foci. We
      find that SHMT2 activity limits that of pyruvate kinase (PKM2) and reduces oxygen
      consumption, eliciting a metabolic state that confers a profound survival
      advantage to cells in poorly vascularized tumour regions. GLDC inhibition impairs
      cells with high SHMT2 levels as the excess glycine not metabolized by GLDC can be
      converted to the toxic molecules aminoacetone and methylglyoxal. Thus, SHMT2 is
      required for cancer cells to adapt to the tumour environment, but also renders
      these cells sensitive to glycine cleavage system inhibition. 

PMID- 25855296
TI  - Lunar tungsten isotopic evidence for the late veneer.
AB  - According to the most widely accepted theory of lunar origin, a giant impact on
      the Earth led to the formation of the Moon, and also initiated the final stage of
      the formation of the Earth's core. Core formation should have removed the highly
      siderophile elements (HSE) from Earth's primitive mantle (that is, the bulk
      silicate Earth), yet HSE abundances are higher than expected. One explanation for
      this overabundance is that a 'late veneer' of primitive material was added to the
      bulk silicate Earth after the core formed. To test this hypothesis, tungsten
      isotopes are useful for two reasons: first, because the late veneer material had
      a different (182)W/(184)W ratio to that of the bulk silicate Earth, and second,
      proportionally more material was added to the Earth than to the Moon. Thus, if a
      late veneer did occur, the bulk silicate Earth and the Moon must have different
      (182)W/(184)W ratios. Moreover, the Moon-forming impact would also have created
      (182)W differences because the mantle and core material of the impactor with
      distinct (182)W/(184)W would have mixed with the proto-Earth during the giant
      impact. However the (182)W/(184)W of the Moon has not been determined precisely
      enough to identify signatures of a late veneer or the giant impact. Here, using
      more-precise measurement techniques, we show that the Moon exhibits a (182)W
      excess of 27 +/- 4 parts per million over the present-day bulk silicate Earth.
      This excess is consistent with the expected (182)W difference resulting from a
      late veneer with a total mass and composition inferred from HSE systematics.
      Thus, our data independently show that HSE abundances in the bulk silicate Earth
      were established after the giant impact and core formation, as predicted by the
      late veneer hypothesis. But, unexpectedly, we find that before the late veneer,
      no (182)W anomaly existed between the bulk silicate Earth and the Moon, even
      though one should have arisen through the giant impact. The origin of the
      homogeneous (182)W of the pre-late-veneer bulk silicate Earth and the Moon is
      enigmatic and constitutes a challenge to current models of lunar origin. 

PMID- 25855295
TI  - Crystal structures of the human adiponectin receptors.
AB  - Adiponectin stimulation of its receptors, AdipoR1 and AdipoR2, increases the
      activities of 5' AMP-activated protein kinase (AMPK) and peroxisome proliferator
      activated receptor (PPAR), respectively, thereby contributing to healthy
      longevity as key anti-diabetic molecules. AdipoR1 and AdipoR2 were predicted to
      contain seven transmembrane helices with the opposite topology to G-protein
      coupled receptors. Here we report the crystal structures of human AdipoR1 and
      AdipoR2 at 2.9 and 2.4 A resolution, respectively, which represent a novel class
      of receptor structure. The seven-transmembrane helices, conformationally distinct
      from those of G-protein-coupled receptors, enclose a large cavity where three
      conserved histidine residues coordinate a zinc ion. The zinc-binding structure
      may have a role in the adiponectin-stimulated AMPK phosphorylation and UCP2
      upregulation. Adiponectin may broadly interact with the extracellular face,
      rather than the carboxy-terminal tail, of the receptors. The present information
      will facilitate the understanding of novel structure-function relationships and
      the development and optimization of AdipoR agonists for the treatment of obesity
      related diseases, such as type 2 diabetes. 

PMID- 25855297
TI  - Structure of the TRPA1 ion channel suggests regulatory mechanisms.
AB  - The TRPA1 ion channel (also known as the wasabi receptor) is a detector of
      noxious chemical agents encountered in our environment or produced endogenously
      during tissue injury or drug metabolism. These include a broad class of
      electrophiles that activate the channel through covalent protein modification.
      TRPA1 antagonists hold potential for treating neurogenic inflammatory conditions
      provoked or exacerbated by irritant exposure. Despite compelling reasons to
      understand TRPA1 function, structural mechanisms underlying channel regulation
      remain obscure. Here we use single-particle electron cryo- microscopy to
      determine the structure of full-length human TRPA1 to ~4 A resolution in the
      presence of pharmacophores, including a potent antagonist. Several unexpected
      features are revealed, including an extensive coiled-coil assembly domain
      stabilized by polyphosphate co-factors and a highly integrated nexus that
      converges on an unpredicted transient receptor potential (TRP)-like allosteric
      domain. These findings provide new insights into the mechanisms of TRPA1
      regulation, and establish a blueprint for structure-based design of analgesic and
      anti-inflammatory agents. 

PMID- 25855298
TI  - Recovery potential of the world's coral reef fishes.
AB  - Continuing degradation of coral reef ecosystems has generated substantial
      interest in how management can support reef resilience. Fishing is the primary
      source of diminished reef function globally, leading to widespread calls for
      additional marine reserves to recover fish biomass and restore key ecosystem
      functions. Yet there are no established baselines for determining when these
      conservation objectives have been met or whether alternative management
      strategies provide similar ecosystem benefits. Here we establish empirical
      conservation benchmarks and fish biomass recovery timelines against which coral
      reefs can be assessed and managed by studying the recovery potential of more than
      800 coral reefs along an exploitation gradient. We show that resident reef fish
      biomass in the absence of fishing (B0) averages ~1,000 kg ha(-1), and that the
      vast majority (83%) of fished reefs are missing more than half their expected
      biomass, with severe consequences for key ecosystem functions such as predation.
      Given protection from fishing, reef fish biomass has the potential to recover
      within 35 years on average and less than 60 years when heavily depleted. Notably,
      alternative fisheries restrictions are largely (64%) successful at maintaining
      biomass above 50% of B0, sustaining key functions such as herbivory. Our results
      demonstrate that crucial ecosystem functions can be maintained through a range of
      fisheries restrictions, allowing coral reef managers to develop recovery plans
      that meet conservation and livelihood objectives in areas where marine reserves
      are not socially or politically feasible solutions. 

PMID- 25855299
TI  - Tungsten isotopic evidence for disproportional late accretion to the Earth and
      Moon.
AB  - Characterization of the hafnium-tungsten systematics ((182)Hf decaying to (182)W
      and emitting two electrons with a half-life of 8.9 million years) of the lunar
      mantle will enable better constraints on the timescale and processes involved in
      the currently accepted giant-impact theory for the formation and evolution of the
      Moon, and for testing the late-accretion hypothesis. Uniform, terrestrial-mantle
      like W isotopic compositions have been reported among crystallization products of
      the lunar magma ocean. These observations were interpreted to reflect formation
      of the Moon and crystallization of the lunar magma ocean after (182)Hf was no
      longer extant-that is, more than about 60 million years after the Solar System
      formed. Here we present W isotope data for three lunar samples that are more
      precise by a factor of >=4 than those previously reported. The new data reveal
      that the lunar mantle has a well-resolved (182)W excess of 20.6 +/- 5.1 parts per
      million (+/-2 standard deviations), relative to the modern terrestrial mantle.
      The offset between the mantles of the Moon and the modern Earth is best explained
      by assuming that the W isotopic compositions of the two bodies were identical
      immediately following formation of the Moon, and that they then diverged as a
      result of disproportional late accretion to the Earth and Moon. One implication
      of this model is that metal from the core of the Moon-forming impactor must have
      efficiently stripped the Earth's mantle of highly siderophile elements on its way
      to merge with the terrestrial core, requiring a substantial, but still poorly
      defined, level of metal-silicate equilibration. 

PMID- 25855301
TI  - Single-lumen tunneled catheter: An old but useful option.
AB  - We report a case of long-term uneventful catheter use in a patient with previous
      recurrent vascular access dysfunction and infection. A single-lumen tunneled
      catheter was inserted into the left internal jugular vein after a failed attempt
      of dual-lumen permanent catheter placement. The follow-up since device
      implantation has exceeded 5 years without any complications related to vascular
      access. 

PMID- 25855302
TI  - Co-spinning of Silver Nanoparticles with Nisin Increases the Antimicrobial
      Spectrum of PDLLA: PEO Nanofibers.
AB  - Silver nanoparticles (AgNPs), synthesized using N,N-dimethylformamide (DMF), were
      electrospun with nisin in a 50:50 blend of 24 % (w/v) poly(D,L-lactide) (PDLLA)
      and poly(ethylene oxide) (PEO). Addition of AgNPs decreased the average diameter
      of the nanofibers [silver nanofibers (SF)] from 588 +/- 191 to 281 +/- 64 nm, or
      to 288 +/- 63 nm when nisin was co-spun with AgNPs. Nanofibers containing AgNO3
      (SF) had a beads-on-string structure, whereas nanofibers with AgNPs and nisin
      [silver plus nisin nanofibers (SNF)], nanofibers with only nisin [nisin
      nanofibers (NF)], and nanofibers without AgNPs and nisin [control nanofibers] had
      a uniform structure. The irregular topography was confirmed by atomic force
      microscopy. No interactions occurred between silver, nisin, PDLLA, and PEO, as
      confirmed with Fourier transform infrared spectroscopy. Most of the AgNPs (18 +/-
      2.8 ppm) and nisin (78.1 +/- 1.2 ug/ml) were released within the first 2 h. SF
      and SNF inhibited the growth of gram-positive and gram-negative bacteria, whereas
      NF failed to inhibit gram-negative bacteria. A wound dressing with broad-spectrum
      antimicrobial activity may be developed by the incorporation of nanofibers
      containing a combination of AgNPs and nisin. 

PMID- 25855300
TI  - Viraemia suppressed in HIV-1-infected humans by broadly neutralizing antibody
      3BNC117.
AB  - HIV-1 immunotherapy with a combination of first generation monoclonal antibodies
      was largely ineffective in pre-clinical and clinical settings and was therefore
      abandoned. However, recently developed single-cell-based antibody cloning methods
      have uncovered a new generation of far more potent broadly neutralizing
      antibodies to HIV-1 (refs 4, 5). These antibodies can prevent infection and
      suppress viraemia in humanized mice and nonhuman primates, but their potential
      for human HIV-1 immunotherapy has not been evaluated. Here we report the results
      of a first-in-man dose escalation phase 1 clinical trial of 3BNC117, a potent
      human CD4 binding site antibody, in uninfected and HIV-1-infected individuals.
      3BNC117 infusion was well tolerated and demonstrated favourable pharmacokinetics.
      A single 30 mg kg(-1) infusion of 3BNC117 reduced the viral load in HIV-1
      infected individuals by 0.8-2.5 log10 and viraemia remained significantly reduced
      for 28 days. Emergence of resistant viral strains was variable, with some
      individuals remaining sensitive to 3BNC117 for a period of 28 days. We conclude
      that, as a single agent, 3BNC117 is safe and effective in reducing HIV-1
      viraemia, and that immunotherapy should be explored as a new modality for HIV-1
      prevention, therapy and cure.

PMID- 25855303
TI  - Prevalence and Characterization of Cronobacter spp. from Various Foods, Medicinal
      Plants, and Environmental Samples.
AB  - Dairy or non-dairy based products were explored to determine the prevalence,
      molecular characterization, and antibiotic susceptibility of Cronobacter spp. The
      isolation was done as per ISO 22964:2006 on chromogenic media followed by further
      confirmation by biochemical- and 16S rRNA-based identification. From 219 samples,
      the chromogenic agar assay and biochemical tests yielded presumptive 45 isolates.
      Among them, only 36 isolates showed 282 bp band amplified from ITS-G gene
      confirming as Cronobacter sakazakii. The Cronobacter spp. prevalence was highest
      in herbs and spices (34 %) while environmental samples had contamination rates of
      23 % indicating plants as a possible reservoir of this pathogen. All the isolates
      were resistant to beta-lactam derivatives (68 %), macrolides (88.6 %), and
      aminoglycosides (79.9 %) but susceptible to phenicoles (31.6 %) and tetracyclines
      (15 %) derivatives. The results emphasize the screening of plant materials before
      their incorporation in food matrices. 

PMID- 25855304
TI  - Modulation of muscle metaboreceptor activation upon sweating and cutaneous
      vascular responses to rising core temperature in humans.
AB  - The present study investigated the role of muscle metaboreceptor activation on
      human thermoregulation by measuring core temperature thresholds and slopes for
      sweating and cutaneous vascular responses during passive heating associated with
      central and peripheral mechanisms. Six male and eight female subjects inserted
      their lower legs into hot water (43 degrees C) while wearing a water perfusion
      suit on the upper body (34 degrees C). One minute after immersion, an isometric
      handgrip exercise--40% of maximum voluntary contraction-was conducted for 1.5 min
      in both control and experimental conditions, while postexercise occlusion was
      performed in the experimental condition only for 9 min. The postexercise forearm
      occlusion during passive heating consistently stimulated muscle metaboreceptors,
      as implicated by significantly elevated mean arterial blood pressure throughout
      the experimental period (P <0.05). Stimulation of the forearm muscle
      metaboreceptors increased sweating and cutaneous vascular responses during
      passive heating, and was associated with significant reductions in esophageal
      temperature threshold of sweating and cutaneous vasodilation (Delta threshold,
      sweating: 0.33 +/- 0.05 and 0.16 +/- 0.04 degrees C, cutaneous vascular
      conductance: 0.38 +/- 0.08 and 0.16 +/- 0.05 degrees C for control and
      experimental groups, respectively, P < 0.05). The slopes of these responses were
      not different between the conditions. These results suggest that muscle
      metaboreceptor activation in the forearm accelerates sweating and cutaneous
      vasodilation during passive heating associated with a reduction in core
      temperature thresholds and may be related to central mechanisms controlling heat
      loss responses.

PMID- 25855305
TI  - High-intensity interval and endurance training are associated with divergent
      skeletal muscle adaptations in a rodent model of hypertension.
AB  - Skeletal muscle is extremely adaptable to a variety of metabolic challenges, as
      both traditional moderate-intensity endurance (ET) and high-intensity interval
      training (HIIT) increases oxidative potential in a coordinated manner. Although
      these responses have been clearly demonstrated in healthy individuals, it remains
      to be determined whether both produce similar responses in the context of
      hypertension, one of the most prevalent and costly diseases worldwide. Therefore,
      in the current study, we used the Dahl sodium-sensitive rat, a model of
      hypertension, to determine the molecular responses to 4 wk of either ET or HIIT
      in the red (RG) and white gastrocnemius (WG) muscles. In the RG, both ET and HIIT
      increased the content of electron transport chain proteins and increased
      succinate dehydrogenase (SDH) content in type I fibers. Although both intensities
      of exercise shifted fiber type in RG (increased IIA, decreased IIX), only HIIT
      was associated with a reduction in endothelial nitric oxide synthase and an
      increase in HIF-1alpha proteins. In the WG, both ET and HIIT increased markers of
      the electron transport chain; however, HIIT decreased SDH content in a fiber
      specific manner. ET increased type IIA, decreased IIB fibers, and increased
      capillarization, while, in contrast, HIIT increased the percentage of IIB fibers,
      decreased capillary-to-fiber ratios, decreased endothelial nitric oxide synthase,
      and increased hypoxia inducible factor-1alpha (HIF-1alpha) protein. Altogether,
      these data show that unlike in healthy animals, ET and HIIT have divergent
      effects in the skeletal muscle of hypertensive rats. This suggests ET may be
      optimal at improving the oxidative capacity of skeletal muscle in animals with
      hypertension. 

PMID- 25855306
TI  - Five years of data diuresis: what have WEH learned?
AB  - This year represents the fifth annual Data Diuresis session of the Water and
      Electrolyte Homeostasis (WEH) section of the American Physiological Society (APS)
      at the 2015 Experimental Biology meeting. As opposed to taking a single organ
      approach to the study of physiology, the WEH section employs an integrative
      approach to encompass how the different organ systems interact to regulate
      numerous physiological and pathophysiological processes. The goal of this
      minireview is to highlight the broad spectrum of research themes that were
      presented over the first five years of Data Diuresis. Presentation topics include
      (but are not limited to) oxidative stress, inflammation, obesity, pregnancy, and
      hypertension spanning the brain, heart and vasculature, and kidney. WEH
      researchers continue to impact and help drive the direction of physiological
      research across multiple disciplines, leaving us excited to see what the next
      five years of Data Diuresis will bring. 

PMID- 25855307
TI  - Impaired oxidative capacity due to decreased CPT1b levels as a contributing
      factor to fat accumulation in obesity.
AB  - To characterize mechanisms responsible for fat accumulation we used a selectively
      bred obesity-prone (OP) and obesity-resistant (OR) rat model where the rats were
      fed a Western diet for 76 days. Body composition was assessed by magnetic
      resonance imaging scans, and as expected, the OP rats developed a higher degree
      of fat accumulation compared with OR rats. Indirect calorimetry showed that the
      OP rats had higher respiratory exchange ratio (RER) compared with OR rats,
      indicating an impaired ability to oxidize fat. The OP rats had lower expression
      of carnitine palmitoyltransferase 1b in intra-abdominal fat, and higher
      expression of stearoyl-CoA desaturase 1 in subcutaneous fat compared with OR
      rats, which could explain the higher fat accumulation and RER values. Basal
      metabolic parameters were also examined in juvenile OP and OR rats before and
      during the introduction of the Western diet. Juvenile OP rats likewise had higher
      RER values, indicating that this trait may be a primary and contributing factor
      to their obese phenotype. When the adult obese rats were exposed to the
      orexigenic and adipogenic hormone ghrelin, we observed increased RER values in
      both OP and OR rats, while OR rats were more sensitive to the orexigenic effects
      of ghrelin as well as ghrelin-induced attenuation of activity and energy
      expenditure. Thus increased fat accumulation characterizing obesity may be caused
      by impaired oxidative capacity due to decreased carnitine palmitoyltransferase 1b
      levels in the white adipose tissue, whereas ghrelin sensitivity did not seem to
      be a contributing factor. 

PMID- 25855308
TI  - Central alterations of neuromuscular function and feedback from group III-IV
      muscle afferents following exhaustive high-intensity one-leg dynamic exercise.
AB  - The aims of this investigation were to describe the central alterations of
      neuromuscular function induced by exhaustive high-intensity one-leg dynamic
      exercise (OLDE, study 1) and to indirectly quantify feedback from group III-IV
      muscle afferents via muscle occlusion (MO, study 2) in healthy adult male humans.
      We hypothesized that these central alterations and their recovery are associated
      with changes in afferent feedback. Both studies consisted of two time-to
      exhaustion tests at 85% peak power output. In study 1, voluntary activation level
      (VAL), M-wave, cervicomedullary motor evoked potential (CMEP), motor evoked
      potential (MEP), and MEP cortical silent period (CSP) of the knee extensor
      muscles were measured. In study 2, mean arterial pressure (MAP) and leg muscle
      pain were measured during MO. Measurements were performed preexercise, at
      exhaustion, and after 3 min recovery. Compared with preexercise values, VAL was
      lower at exhaustion (-13 +/- 13%, P < 0.05) and after 3 min of recovery (-6 +/-
      6%, P = 0.05). CMEP area/M area was lower at exhaustion (-38 +/- 13%, P < 0.01)
      and recovered after 3 min. MEP area/M area was higher at exhaustion (+25 +/- 27%,
      P < 0.01) and after 3 min of recovery (+17 +/- 20%, P < 0.01). CSP was higher
      (+19 +/- 9%, P < 0.01) only at exhaustion and recovered after 3 min. Markers of
      afferent feedback (MAP and leg muscle pain during MO) were significantly higher
      only at exhaustion. These findings suggest that the alterations in spinal
      excitability and CSP induced by high-intensity OLDE are associated with an
      increase in afferent feedback at exhaustion, whereas central fatigue does not
      fully recover even when significant afferent feedback is no longer present.

PMID- 25855309
TI  - From Tusko to Titin: the role for comparative physiology in an era of molecular
      discovery.
AB  - As we approach the centenary of the term "comparative physiology," we reexamine
      its role in modern biology. Finding inspiration in Krogh's classic 1929 paper, we
      first look back to some timeless contributions to the field. The obvious and
      fascinating variation among animals is much more evident than is their shared
      physiological unity, which transcends both body size and specific adaptations.
      The "unity in diversity" reveals general patterns and principles of physiology
      that are invisible when examining only one species. Next, we examine selected
      contemporary contributions to comparative physiology, which provides the context
      in which reductionist experiments are best interpreted. We discuss the sometimes
      surprising insights provided by two comparative "athletes" (pronghorn and
      rattlesnakes), which demonstrate 1) animals are not isolated molecular mechanisms
      but highly integrated physiological machines, a single "rate-limiting" step may
      be exceptional; and 2) extremes in nature are rarely the result of novel
      mechanisms, but rather employ existing solutions in novel ways. Furthermore,
      rattlesnake tailshaker muscle effectively abolished the conventional view of
      incompatibility of simultaneous sustained anaerobic glycolysis and oxidative ATP
      production. We end this review by looking forward, much as Krogh did, to suggest
      that a comparative approach may best lend insights in unraveling how skeletal
      muscle stores and recovers mechanical energy when operating cyclically. We
      discuss and speculate on the role of the largest known protein, titin (the third
      muscle filament), as a dynamic spring capable of storing and recovering elastic
      recoil potential energy in skeletal muscle. 

PMID- 25855311
TI  - Medical interventions for fungal keratitis.
AB  - BACKGROUND: Fungal keratitis is a fungal infection of the cornea. It is common in
      lower income countries, particularly in agricultural areas but relatively
      uncommon in higher income countries. Although there are medications available,
      their effectiveness is unclear. OBJECTIVES: To assess the effects of different
      antifungal drugs in the management of fungal keratitis. SEARCH METHODS: We
      searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials
      Register) (2015, Issue 2), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non
      Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to March
      2015), EMBASE (January 1980 to March 2015), Latin American and Caribbean Health
      Sciences Literature Database (LILACS) (January 1982 to March 2015), the ISRCTN
      registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov
      (www.clinicaltrials.gov) and the World Health Organization (WHO) International
      Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did
      not use any date or language restrictions in the electronic searches for trials.
      We last searched the electronic databases on 16 March 2015. SELECTION CRITERIA:
      We included randomised controlled trials of medical therapy for fungal keratitis.
      DATA COLLECTION AND ANALYSIS: Two review authors selected studies for inclusion
      in the review, assessed trials for risk of bias and extracted data. The primary
      outcome was clinical cure at two to three months. Secondary outcomes included
      best-corrected visual acuity, time to clinical cure, compliance with treatment,
      adverse outcomes and quality of life. MAIN RESULTS: We included 12 trials in this
      review; 10 trials were conducted in India, one in Bangladesh and one in Egypt.
      Seven of these trials were at high risk of bias in one or more domains, two of
      these studies were at low risk of bias in all domains. Participants were
      randomised to the following comparisons: topical 5% natamycin compared to topical
      1% voriconazole; topical 5% natamycin compared to topical 2% econazole; topical
      5% natamycin compared to topical chlorhexidine gluconate (0.05%, 0.1% and 0.2%);
      topical 1% voriconazole compared to intrastromal voriconazole 50 g/0.1 mL (both
      treatments combined with topical 5% natamycin); topical 1% voriconazole combined
      with oral voriconazole compared to both oral voriconazole and oral itraconazole
      (both combined with topical 5% natamycin); topical 1% itraconazole compared to
      topical 1% itraconazole combined with oral itraconazole; topical amphotericin B
      compared to topical amphotericin B combined with subconjunctival injection of
      fluconazole; intracameral injection of amphotericin B with conventional treatment
      compared to conventional treatment alone (severe fungal ulcers); topical 0.5% and
      1% silver sulphadiazine compared to topical 1% miconazole. Overall the results
      were inconclusive because for most comparisons only one small trial was
      available. The exception was the comparison of topical natamycin and topical
      voriconazole for which three trials were available. In one of these trials
      clinical cure (healed ulcer) was reported in all 15 people allocated to natamycin
      and in 14/15 people allocated to voriconazole (risk ratio (RR) 1.07; 95%
      confidence interval (CI) 0.89 to 1.28, low quality evidence). In one trial people
      randomised to natamycin were more likely to have a microbiological cure at six
      days (RR 1.64; 95% CI 1.38 to 1.94, 299 participants). On average, people
      randomised to natamycin had better spectacle-corrected visual acuity at two to
      three months compared to people randomised to voriconazole but the estimate was
      uncertain and the 95% confidence intervals included 0 (no difference) (mean
      difference -0.12 logMAR, 95% CI -0.31 to 0.06, 434 participants; 3 studies, low
      quality evidence) and a decreased risk of corneal perforation or therapeutic
      penetrating keratoplasty, or both (RR 0.61; 95% CI 0.40 to 0.94, 434
      participants, high quality evidence). There was inconclusive evidence on time to
      clinical cure. Compliance with treatment and quality of life were not reported.
      One trial comparing natamycin and voriconazole found the effect of treatment
      greater in Fusarium species, but this subgroup analysis was not prespecified by
      this review. AUTHORS' CONCLUSIONS: The trials included in this review were of
      variable quality and were generally underpowered. There is evidence that
      natamycin is more effective than voriconazole in the treatment of fungal ulcers.
      Future research should evaluate treatment effects according to fungus species.

PMID- 25855310
TI  - The effect of spinal cord injury on the neurochemical properties of vagal sensory
      neurons.
AB  - The vagus nerve is composed primarily of nonmyelinated sensory neurons whose cell
      bodies are located in the nodose ganglion (NG). The vagus has widespread
      projections that supply most visceral organs, including the bladder. Because of
      its nonspinal route, the vagus nerve itself is not directly damaged from spinal
      cord injury (SCI). Because most viscera, including bladder, are dually innervated
      by spinal and vagal sensory neurons, an impact of SCI on the sensory component of
      vagal circuitry may contribute to post-SCI visceral pathologies. To determine
      whether SCI, in male Wistar rats, might impact neurochemical characteristics of
      NG neurons, immunohistochemical assessments were performed for P2X3 receptor
      expression, isolectin B4 (IB4) binding, and substance P expression, three known
      injury-responsive markers in sensory neuronal subpopulations. In addition to
      examining the overall population of NG neurons, those innervating the urinary
      bladder also were assessed separately. All three of the molecular markers were
      represented in the NG from noninjured animals, with the majority of the neurons
      binding IB4. In the chronically injured rats, there was a significant increase in
      the number of NG neurons expressing P2X3 and a significant decrease in the number
      binding IB4 compared with noninjured animals, a finding that held true also for
      the bladder-innervating population. Overall, these results indicate that vagal
      afferents, including those innervating the bladder, display neurochemical
      plasticity post-SCI that may have implications for visceral homeostatic
      mechanisms and nociceptive signaling. 

PMID- 25855312
TI  - Current therapeutic strategies for multiple myeloma.
AB  - The introduction of novel molecular targeting agents against multiple myeloma has
      dramatically and rapidly changed the therapeutic strategies for this incurable
      hematologic disease. Novel agents such as thalidomide, bortezomib and
      lenalidomide have significantly improved the response rate, progression-free
      survival, and overall survival compared with conventional chemotherapies, and
      made it easy to control the disease for longer periods of time. Initial therapies
      for newly diagnosed myeloma patients depend on the individual's clinical
      condition. Induction therapy with novel agents and high-dose chemotherapy
      followed by autologous stem cell transplantation is a standard therapy for newly
      diagnosed younger myeloma patients. On the other hand, several combinations of
      novel agents and other drugs (melphalan, prednisone, dexamethasone, etc.) are
      widely used as initial therapy for transplantation-ineligible myeloma patients.
      Although the clinical advantage of maintenance therapy after induction therapy
      has been reported, it is not recommend in routine practice. Maintenance therapy
      would be an option for some patients. Despite the significant improvements with
      the use of novel agents, the majority of patients eventually relapse. A number of
      treatment options including novel agents, which demonstrated marked clinical
      effects, are reported in the setting of salvage therapy. The choice of
      appropriate therapy for relapsed or refractory patients must take the disease
      status or patient status in consideration. Furthermore, a new generation of novel
      agents such as pomalidomide, carfilzomib or panobinostat has recently become
      available for relapsed or refractory myeloma. It is necessary to determine the
      optimal combination of drugs, administration timing and patients to be treated in
      future clinical trials. 

PMID- 25855314
TI  - An Impedance-Based Method to Determine Reconstitution Time for Freeze-Dried
      Pharmaceuticals.
AB  - The reconstitution of freeze-dried products is usually determined by visual
      inspection with the naked eye. This can inevitably lead to significant
      variability in the ability to detect complete reconstitution of the dried solid.
      It was thus the goal of our study to assess an automated method to monitor
      reconstitution of a freeze-dried protein drug product in its primary packaging. A
      newly developed measuring device was used to measure impedance. This was achieved
      by detecting minor changes in impedance of the reconstitution medium, which
      occurred because of solid material dissolving during the dissolution process.
      This measurement system was capable of consistently detecting the dissolution of
      the last visible residues of freeze-dried lyophilisates. The endpoint of
      reconstitution was defined at an impedance change of less than 1 Omega for at
      least 7 s. Finally, we compared reconstitution times determined by the automated
      impedance method with results obtained by a visual method. In contrast to human
      operators, the new method delivered both accurate and precise results. Besides
      detection of the reconstitution endpoint, the impedance method and apparatus can
      monitor reconstitution endpoints as well as reconstitution kinetics. This
      standardized method can therefore advantageously be used for the determination of
      the reconstitution endpoint.

PMID- 25855313
TI  - Efficacy of intraoperative entire-circumferential frozen section analysis of
      lumpectomy margins during breast-conserving surgery for breast cancer.
AB  - BACKGROUND: Intraoperative frozen section analysis of the surgical margins during
      breast-conserving surgery (BCS) for breast cancer can reliably achieve clear
      surgical margins and prevent re-operations. The aim of this study was to assess
      intraoperative entire-circumferential frozen section analysis (IEFSA) of the
      lumpectomy margins during BCS. METHODS: A total of 1029 patients who underwent
      BCS with IEFSA between June 2007 and July 2013 were available for assessment. The
      inner surfaces of the shaved lumpectomy margins were examined as frozen sections
      during BCS. The margins were defined as positive when the cancer cells were
      present within 5 mm from the edge of the outermost margins of the specimens.
      RESULTS: Out of 1029 patients, 312 patients (30.3 %) had positive margins after
      the initial lumpectomy and underwent additional resections during BCS. Fourteen
      patients (1.4 %) underwent mastectomy following the results of additional
      resections during the first surgery. Of 1015 patients who completed BCS, 60
      patients (5.9 %) were found to have positive margins in the final pathology. One
      patient (0.1 %) underwent re-operation after BCS while the residual diseases of
      the other 59 patients were judged to be minimal. Of the 312 patients who were
      judged to have positive margins after the initial lumpectomy with IEFSA, 53
      patients (16.9 %) were found to have negative margins in the final pathology. At
      a median follow-up time of 54.1 months, one patient (0.1 %) had a recurrence of
      breast cancer in the preserved breast. CONCLUSION: IEFSA is useful for preventing
      the need for re-operation and local recurrence after BCS.

PMID- 25855315
TI  - Simultaneous LC-MS/MS determination of five tripterygium pyridine alkaloids in
      dog plasma and its application to their pharmacokinetic study after oral
      administration of tripterygium glycosides tablets.
AB  - A sensitive and selective liquid chromatography tandem mass spectrometric method
      was developed and validated for the simultaneous determination of five pyridine
      alkaloids contained in tripterygium glycosides tablets (triptolide, wilforine,
      wilforgine, wilfording and wilfortrine) in dog plasma. The analysis was carried
      out on a Sepax GP-Phenyl column using a mixture of methanol and 10mmol/L ammonium
      formate buffer solution containing 0.1% formic acid (75:25, v/v) as the mobile
      phase pumped at a flow-rate of 1.0mL/min. All MS data were obtained in the
      positive ESI mode with selective multiple reaction monitoring of ion transitions.
      The method was fully validated to be accurate and precise with a linear range of
      0.2-1000ng/mL for triptolide and 0.05-1000ng/mL for the other four pyridine
      alkaloids. The intra-day and inter-day precisions (relative standard deviation,
      RSD, %) were within 10.6% and 14.0%, respectively, and the relative error (RE, %)
      were all less than 13.1%. The method was successfully applied to multi-components
      pharmacokinetic study of the five pyridine alkaloids in beagle dogs after a
      single oral administration of 3mg/kg and 30mg/kg tripterygium glycosides tablets,
      respectively, and a multiple oral administration of 30mg/kg for 6 consecutive
      days. 

PMID- 25855316
TI  - Determination of cyproheptadine in feeds using molecularly imprinted solid-phase
      extraction coupled with HPLC.
AB  - A novel method was developed for the determination of cyproheptadine in feeds
      using molecularly imprinted solid-phase extraction coupled with high-performance
      liquid chromatography. The polymers were prepared using cyproheptadine as a
      template molecule, methacrylic acid as a functional monomer, ethylene glycol
      dimethacrylate as a cross-linking agent, and dichloromethane as a solvent by bulk
      polymerization. Under the optimum solid-phase extraction conditions, the
      molecular imprinting cartridge can selectively extract and enrich cyproheptadine
      from a variety of feeds. Mean recoveries of cyproheptadine from four kinds of
      feeds spiked at 0.1, 1.0 and 10mgkg(-1) ranged from 85.5% to 96.2%, with intra
      day and inter-day relative standard deviation less than 10%. The calibration
      curve of cyproheptadine was good linear relationship (r>0.9993) within the range
      of 0.1-50MUgmL(-1). The limit of detection (LOD) and the limit of quantification
      (LOQ) were 0.04 and 0.1mgkg(-1), respectively. 

PMID- 25855317
TI  - Comparison of iso-eluotropic mobile phases at different temperatures for the
      separation of triacylglycerols in Non-Aqueous Reversed Phase Liquid
      Chromatography.
AB  - Triacylglycerols (TAGs) are a large class of neutral lipids that naturally occur
      in both plant and animal oils and fats. Their analyses in Non-Aqueous Reversed
      Phase Liquid Chromatography (NARP) require a mixture of weak solvent (mostly
      acetonitrile) and strong solvent. In the present work, we have established
      eluotropic solvent strength scale of several binary mobile phases on C18 bonded
      silica at different temperatures (acetonitrile/methylene chloride,
      acetonitrile/acetone, acetonitrile/ethyl acetate, acetonitrile/propan-2-ol, and
      acetonitrile/butan-1-ol at 25 degrees C, 43 degrees C, 63 degrees C and 85
      degrees C); it is based on the methylene selectivity and the use of homologous
      series. We show that this scale is well suited to the TAGs analysis. The analysis
      of nine seed oils (Aleurites fordii, Calophyllum inophyllum, Glycina max, Olea
      europea, Orbignya olifeira, Pinus koraiensis, Pistacia lentiscus, Punica granatum
      and Ribes nigrum) in iso-eluotropic conditions leads to propose unambiguously the
      couple MeCN/BuOH at 25 degrees C as the best system to separate TAGs. The use of
      butanol, as strong solvent, provides very good TAGs congeners separations and
      avoids the use of chlorinated solvents which gave to this day the best
      separations. 

PMID- 25855318
TI  - Lipidomic analysis of plasma, erythrocytes and lipoprotein fractions of
      cardiovascular disease patients using UHPLC/MS, MALDI-MS and multivariate data
      analysis.
AB  - Differences among lipidomic profiles of healthy volunteers, obese people and
      three groups of cardiovascular disease (CVD) patients are investigated with the
      goal to differentiate individual groups based on the multivariate data analysis
      (MDA) of lipidomic data from plasma, erythrocytes and lipoprotein fractions of
      more than 50 subjects. Hydrophilic interaction liquid chromatography on ultrahigh
      performance liquid chromatography (HILIC-UHPLC) column coupled with electrospray
      ionization mass spectrometry (ESI-MS) is used for the quantitation of four
      classes of polar lipids (phosphatidylethanolamines, phosphatidylcholines,
      sphingomyelins and lysophosphatidylcholines), normal-phase UHPLC-atmospheric
      pressure chemical ionization MS (NP-UHPLC/APCI-MS) is applied for the
      quantitation of five classes of nonpolar lipids (cholesteryl esters,
      triacylglycerols, sterols, 1,3-diacylglycerols and 1,2-diacylglycerols) and the
      potential of matrix-assisted laser desorption/ionization mass spectrometry (MALDI
      MS) is tested for the fast screening of all lipids without a chromatographic
      separation. Obtained results are processed by unsupervised (principal component
      analysis) and supervised (orthogonal partial least squares) MDA approaches to
      highlight the largest differences among individual groups and to identify lipid
      molecules with the highest impact on the group differentiation. 

PMID- 25855319
TI  - 1H and 13C NMR spectral assignments of 18 novel polymethoxylated
      hydroxynaphthopyrazolylchalconoids.

PMID- 25855322
TI  - Correction.

PMID- 25855323
TI  - Foci of Entotic Nuclei in Different Grades of Noninherited Renal Cell Cancers.
AB  - We report here an intriguing pattern in nuclear appearance of renal clear cell
      cancer. In low grade clear cell cancer, detailed examination showed that in many
      cells, two or more nuclei were within the confines of a single cell membrane.
      This likely resulted from a cell being contained within its neighboring cell.
      Consequently, this resulted in appearance of multicellularity. This appearance of
      the nuclei were not associated with mitotic figures, suggesting that these did
      not result from nuclear fission. Additionally, the cells containing this nuclei
      did not show any evidence of cytokinesis including equatorial tapering,
      suggesting that the process may have resulted from cytokinesis failure. In some
      sections of higher grade clear cell cancer, these appearance were higher, though
      we did not observe any frank syncytium formation. On careful observation, there
      were isolated events of fusion of nuclei within a single cell in different grades
      of renal cell cancers. There occurrence was more frequent in higher grades of
      clear cell renal cancer and metastatic clear cell carcinoma. These features were
      also demonstrable in multiple fields of lower grades of clear cell carcinoma.
      This phenomenon of entosis may contribute to aneuploidy and tumor progression to
      dysplastic stages and genomic instability in renal cancers. Future studies are
      aimed at delineating the cell-cell boundaries and the mechanism contributing to
      this observation, either from peripheral cell engulfing or failure of cytosolic
      division for cell separation.

PMID- 25855324
TI  - Prevalence of and risk factors for gestational diabetes using 1999, 2013 WHO and
      IADPSG criteria upon implementation of a universal one-step screening and
      diagnostic strategy in a sub-Saharan African population.
AB  - OBJECTIVES: To investigate the impact of the new consensus diagnostic criteria on
      the prevalence of gestational diabetes, evaluate risk factors, and missed
      opportunities for diagnosis if selective screening strategy was employed. STUDY
      DESIGN: A prospective observational data of 1059 women with singleton pregnancy
      screened for gestational diabetes between 24 and 32 weeks gestation in a
      universal one-step screening and diagnostic strategy using 75-g oral glucose
      tolerance testing in an obstetric unit in Nigeria. Logistic regression was used
      to identify risk factors for GDM. RESULTS: The prevalence of gestational diabetes
      in accordance with 1999 WHO, new 2013 WHO modified IADPSG and IADPSG criteria was
      3.8%, 8.1%, 7.5%, and 8.6%, respectively. Overt diabetes was diagnosed in 1.03%
      of the study population. Using the new consensus criteria, approximately 20% of
      GDM cases would have been missed if selective screening strategy was employed.
      Using multivariable analysis, glycosuria [aOR 8.60 (3.29-22.46)] and previous
      poor obstetric outcome [aOR 3.01 (1.23-7.37)] were significantly associated with
      GDM on 1999 WHO criteria. Glycosuria [aOR 2.54 (1.10-6.42)] was the only risk
      significantly associated with increased risk of developing GDM diagnosed based on
      new 2013 and IADPSG criteria. CONCLUSION: Using the new consensus screening and
      diagnostic guidelines, gestational diabetes is prevalent in our obstetric
      population. Missed opportunities exist with selective screening approach.

PMID- 25855325
TI  - Recombinant FSH increases live birth rates as compared to clomiphene citrate in
      intrauterine insemination cycles in couples with subfertility: a prospective
      randomized study.
AB  - OBJECTIVE: To compare the efficacy of intrauterine insemination (IUI) cycles
      undergoing ovarian hyperstimulation with recombinant FSH (rFSH) or clomiphene
      citrate (CC) in couples with unexplained and male subfertility. STUDY DESIGN: Two
      hundred and nineteen subfertile couples were enrolled in this randomized
      prospective study. Patients were randomly assigned to receive 75IU rFSH or 100mg
      CC for two cycles. Cycles with more than four dominant follicles and/or serum E2
      levels higher than 1500pg/ml were cancelled. Primary outcomes were live birth
      rates per patient and per cycle, secondary outcomes were clinical and multiple
      pregnancy rates. RESULTS: One hundred and nine women received rFSH and 110
      received CC. Both cumulative clinical pregnancy and live birth rates per patient
      were significantly higher in gonadotropin group (43.1% and 37.6%) as compared to
      CC group (28.2% and 20%) (p<0.05 and p<0.01, respectively). Live birth rate per
      cycle were significantly higher in gonadotropin group (24.3%) in comparison with
      CC group (13.8%) (p<0.05). However, clinical pregnancy rate per cycle was not
      different between groups (28.4% vs 20%) (p>0.05). There was no significant
      difference between gonadotropin and CC group groups in terms of multiple
      pregnancy rates (10.4% vs 12.5%, p>0.05). Continuous variables were compared with
      Student's t test. Categorical variables were compared with Chi square test.
      CONCLUSION: rFSH has significantly higher cumulative clinical pregnancy and live
      birth rates when compared to CC with similar multiple pregnancy rates in
      subfertile patients undergoing IUI.

PMID- 25855326
TI  - Urethral bulking agents versus other surgical procedures for the treatment of
      female stress urinary incontinence: a systematic review and meta-analysis.
AB  - Bulking agents provide an alternative option in the management of women with
      stress urinary incontinence and they seem to have an important role in the
      management flow chart of SUI. However, evidence on this issue is scanty. The most
      important aspect is to understand whether bulking agents are comparable with the
      other first-line anti-incontinence surgical procedure (MUS, Burch colposuspension
      and pubovaginal slings). Hence, the primary aim of the current review was to
      assess the objective and subjective outcomes of bulking agents in comparison with
      the other surgical procedures for the treatment of SUI. PubMed and Medline were
      systematically searched and we included studies evaluating the use of bulking
      agents in comparison with other surgical approaches for either primary or
      recurrent treatment of female SUI. Three studies meeting the inclusion criteria
      were identified. Two of these studies were RCTs evaluating the use of bulking
      agents versus other surgical procedures for the treatment of primary female SUI;
      the remnant article was a retrospective cohort study that compared the
      effectiveness and safety of repeat midurethral sling with urethral bulking after
      failed midurethral sling. The combined results of all analyses showed that the
      objective recurrence rate of peri- or trans-urethral injections is significantly
      higher in comparison with the other surgical procedures. Similar findings were
      observed when considering separately the treatment for primary or recurrent SUI.
      Furthermore, lower subjective recurrence rate was observed among patients
      undergoing other surgical treatment in comparison with those undergoing bulking
      agents; however, this trend was not statistically significant. Moreover, patients
      undergoing injection of bulking agents experienced a lower rate of voiding
      dysfunctions in comparison to the control group. According to current evidence,
      bulking agents should not be proposed as first-line treatment in those women
      seeking permanent cure for both primary and recurrent SUI. However, the
      effectiveness of a procedure should be balanced with its invasiveness and
      patients' expectations. Bulking agents are a minimally invasive approach to treat
      SUI and their use should be considered as an alternative strategy particularly in
      special conditions: patients who are fragile, in those who do not wish to have
      surgery, or in whom surgical options are restricted (postoperatively, after
      irradiation). 

PMID- 25855327
TI  - Acute compartment syndrome occurring in forearm with relatively small amount of
      hematoma following transradial coronary intervention.
AB  - A 59-year-old female with angina pectoris successfully underwent percutaneous
      coronary intervention via the right radial artery. She complained of right
      forearm pain and numbness 4.5 h after the procedure. Though the swelling in her
      right arm seemed relatively mild, pressure measurement showed significant
      increase of internal forearm pressure. She developed acute compartment syndrome
      in the right forearm, and fasciotomy was performed immediately. The weight of
      subcutaneous hematoma in her right arm was approximately 100 g. Symptoms of
      paralysis and the impairment of perception remained for some time, but had
      completely recovered 4 months post-surgery. 

PMID- 25855328
TI  - Chemical compositions and antibacterial activity of extracts obtained from the
      inflorescences of Cirsium canum (L.) all.
AB  - The aim of this study was to investigate phenolic acids and flavonoids in
      methanolic, dichloromethane, acetone and ethyl acetate extracts and fractions
      from inflorescences of Cirsium canum (L.). RP-HPLC analysis enabled
      identification of the following: chlorogenic acid, caffeic acid, p-coumaric acid,
      protocatechuic acid, p-hydroxybenzoic acid, vanillic acid, syringic acid, trans
      cinnamic acid, luteolin-7-glucoside, apigenin-7-glucoside, kaempferol-3
      glucoside, linarin, apigenin, rutoside, luteolin and kaempferol. The
      antimicrobial activity of tested extracts was determined in vitro against
      reference microorganisms, including bacteria or fungi, belonging to yeasts. Our
      data showed that the tested extracts had no influence on the growth of the
      reference strains of Gram-negative bacteria and yeasts belonging to Candida spp.
      Among them, the fractions possessed the highest activity against Gram-positive
      bacteria, especially Streptococcus aureus and Streptococcus pneumoniae belonging
      to pathogens and Streptococcus epidermidis, Bacilluscereus and Bacillus subtilis
      belonging to opportunistic microorganisms. 

PMID- 25855329
TI  - Novel ABO gene variants caused by missense mutations in Exon 7 leading to
      discrepant ABO blood typing results.

PMID- 25855330
TI  - New immunotherapies show promise in some patients: physicians try to balance
      optimism with realistic expectations.

PMID- 25855331
TI  - FDA approves Gardasil 9 for more types of HPV.

PMID- 25855332
TI  - Lung cancer alliance praises CMS decision to cover lung cancer screenings.

PMID- 25855333
TI  - Sun behaviors and genes may affect future melanoma risk.

PMID- 25855335
TI  - Intracolonic Administration of the TRPA1 Agonist Allyl Isothiocyanate Stimulates
      Colonic Motility and Defecation in Conscious Dogs.
AB  - BACKGROUND: The aim of the present study was to investigate the effects of the
      intracolonic transient receptor potential (TRP) A1 agonist allyl isothiocyanate
      (AITC) on colonic motility and defecation. METHODS: The effects of AITC
      administered into the proximal colonic lumen on colonic motility and defecation
      were studied in neurally intact dogs equipped with strain-gauge force transducers
      on the colon, with or without various antagonists. Effects of intracolonic AITC
      were also studied in dogs with either transection/re-anastomosis (T/R) between
      the proximal and middle colon and complete extrinsic denervation of an
      ileocolonic segment. RESULTS: AITC increased colonic motility and induced giant
      migrating contractions (GMCs) with defecations in 75% of experiments in neurally
      intact dogs. These effects were inhibited by atropine, hexamethonium,
      ondansetron, and HC-030031 but unaltered by capsazepine. In dogs with T/R, the
      increase in colonic motility was inhibited in the middle-distal colon. In dogs
      with extrinsic denervation, the increase in colonic motility in the distal colon
      was decreased. CONCLUSIONS: Intracolonic AITC stimulates colonic motility and
      defecation via cholinergic, serotonergic, and TRPA1 pathways. Continuity of
      colonic enteric neurons plays an essential role in the intracolonic AITC-induced
      colonic motor response, while extrinsic nerves are important in occurrence and
      propagation of GMCs.

PMID- 25855336
TI  - Simultaneous Chemical and Optical Patterning of Polyacrylonitrile Film by Vapor
      Based Reaction.
AB  - The surface of polyacrylonitrile (PAN) film is treated with ethyleneamines (EDA)
      in a simple chemical vapor phase reaction. Successful introduction of amine
      functional groups on the cyano group of PAN backbone is verified by FT-IR and NMR
      measurements. Further UV-vis and photoluminescence analyses show a red shift of
      the emission peak after repeated EDA treatment, which might be attributed to the
      formation of imine conjugation from newly formed carbon-nitrogen bonds on the PAN
      backbone. Further confocal laser scanning microscopy reveals that selective
      patterning of EDA on PAN films is possible via local polydimethylsiloxane
      masking. The results indicate that both chemical and optical patterning on PAN
      film can be realized via a single reaction and show the potential of this novel
      methodology in selective patterning. 

PMID- 25855337
TI  - Engagement of Traditional Healers and Birth Attendants as a Controversial
      Proposal to Extend the HIV Health Workforce.
AB  - "Medical pluralism" is the use of multiple health systems and is common among
      people living with HIV/AIDS in sub-Saharan Africa. Healers and traditional birth
      attendants (TBAs) often are a patient's first and/or preferred line of treatment;
      this often results in delayed, interrupted, or abandoned diagnosis and therapy.
      Literature from the study of medical pluralism suggests that HIV care and
      treatment programs are infrequently and inconsistently engaging healers around
      the world. Mistrust and misunderstanding among patients, clinical providers, and
      traditional practitioners make the development of effective partnerships
      difficult, particularly regarding early HIV diagnosis and antiretroviral therapy.
      We provide recommendations for the development of successful collaboration health
      workforce efforts based on both published articles and case studies from our work
      in rural Mozambique. 

PMID- 25855338
TI  - Sustained High HIV Incidence in Young Women in Southern Africa: Social,
      Behavioral, and Structural Factors and Emerging Intervention Approaches.
AB  - Young women in southern Africa experience some of the highest incidence rates of
      HIV infection in the world. Across southern Africa, HIV prevalence among women
      increases rapidly between the teenage years and young adulthood. Adult HIV
      prevalence is 16.8 % in South Africa, 23 % in Botswana, 23 % in Lesotho, and 26.5
      % in Swaziland. Existing research has illuminated some of the key social,
      behavioral, and structural factors associated with young women's disproportionate
      HIV risk, including gendered social norms that advantage male power in sexual
      relationships and age disparities in relationships between younger women and
      older male partners. Important structural factors include the region's history of
      labor migration and legacy of family disruption, and entrenched social and
      economic inequalities. New interventions are emerging to address these high
      levels of HIV risk in the key population of young women, including structural
      interventions, biomedical prevention such as PrEP, and combined HIV prevention
      approaches.

PMID- 25855339
TI  - Quality of Care and Service Expansion for HIV Care and Treatment.
AB  - The last two decades have seen exceptional development of antiretroviral
      treatment programs throughout the world. Over 14 million persons are accessing
      antiretroviral treatment (ART) treatment as of early 2015, and life expectancy
      has risen markedly in the most-affected populations. However, large patient
      numbers threaten to overwhelm already over-burdened health care systems and
      retention in care remains suboptimal. Developing innovative strategies to
      alleviate these burdens and retain patients in care remains a challenge.
      Furthermore, despite this expansion, large populations of HIV-infected persons
      remain undiagnosed and are unwilling or unable to access care and treatment
      programs. Marginalized and high-risk populations are particularly in danger of
      remaining outside of care and are also disproportionately affected by HIV. To
      reverse the trend and "fast track" our way out of the epidemic, ambitious
      treatment targets are required, and a concerted effort has to be made to engage
      these populations into care, initiate ART, and attain viral suppression. 

PMID- 25855340
TI  - Counter-regulatory hormone responses to hypoglycaemia in people with type 1
      diabetes after 4 weeks of treatment with liraglutide adjunct to insulin: a
      randomized, placebo-controlled, double-blind, crossover trial.
AB  - AIMS: To investigate the effect of glucagon-like peptide 1 receptor agonist
      liraglutide on the counter-regulatory hormone response to hypoglycaemia in type 1
      diabetes. METHODS: We conducted a randomized, double-blind, placebo-controlled,
      single-centre trial, in which a total of 45 adults with type 1 diabetes [mean +/-
      standard deviation age 34.5 +/- 11.2 years, BMI 23.9 +/- 2.4 kg/m(2) , glycated
      haemoglobin (HbA1c) 7.6 +/- 0.8%, diabetes duration 16.6 +/- 9.4 years] underwent
      a hypoglycaemic clamp after 4 weeks' crossover treatment with once-daily
      liraglutide/placebo added to insulin in one of three liraglutide dose groups: 0.6
      mg (n = 15); 1.2 mg (n = 14); and 1.8 mg (n = 16). The main outcome measure was
      glucagon concentration at nadir plasma glucose (2.5 mmol/l). Clinical outcomes
      were also evaluated. Five participants were withdrawn from the trial; three
      because of adverse events. All participants were included in the analysis.
      RESULTS: Glucagon concentration at nadir plasma glucose was modest, trending
      towards lower concentrations at increasing liraglutide dose versus placebo: 34.7
      versus 38.1 pg/ml, p = 0.555 (0.6 mg); 28.8 versus 37.2 pg/ml, p = 0.126 (1.2
      mg); and 28.4 versus 37.5 pg/ml, p = 0.092 (1.8 mg). There was no difference,
      however, between liraglutide and placebo in incremental change in glucagon during
      hypoglycaemia. Other counter-regulatory hormone levels increased during
      hypoglycaemia with no systematic differences between groups. Glucose infusion
      rates were significantly lower with liraglutide versus placebo during the clamp.
      After 4 weeks' treatment, HbA1c remained unchanged in the liraglutide and placebo
      groups. Greater reductions in insulin dose and body weight were seen with
      liraglutide versus placebo. CONCLUSIONS: Liraglutide did not compromise
      hypoglycaemic responses in type 1 diabetes after 4 weeks' treatment.

PMID- 25855341
TI  - Ongoing risk of thrombosis with factor XI concentrate: 5 years experience in two
      centres.
AB  - INTRODUCTION: Factor XI (FXI) deficiency is the commonest of the rare bleeding
      disorders, affecting 2079 individuals in the United Kingdom. Treatment options
      for bleeding or surgery include antifibrinolytics, fresh frozen plasma or plasma
      derived (pd) FXI concentrates. There were a number of reports of thrombosis
      following treatment with FXI concentrates prior to changes in their manufacturing
      processes made in the mid-1990's. AIMS: The aim of the study was to determine the
      occurrence of adverse events (haemorrhagic and thrombotic) following usage of pd
      FXI concentrates at two large UK haemophilia centres. Retrospective chart review
      of all consecutively treated patients with BPL Factor XI((r)) or Hemoleven((r))
      over a 5-year period (11/06-11/11) was performed. RESULTS: Twenty-nine patients
      (median age = 57.1 years) received treatment over 64 treatment episodes (surgery
      = 56, bleeding = 5, other = 3), using 126 000 U of concentrate. Median baseline
      FXI:C was 9 U dL(-1) (range = <1-51), with 21 having severe and eight partial
      deficiency. BPL Factor XI((r)) was used in 39 episodes (79 110 U) and
      Hemoleven((r)) 25 episodes (46 890 U). There were six clinically significant
      bleeding events, managed either with a single additional dose of FXI concentrate
      (n = 4) or requiring no further intervention (n = 2). One patient required blood
      transfusion and one oral iron replacement. Two thrombotic events (transient
      ischaemic attack and pulmonary emboli), occurred in two patients with severe FXI
      deficiency, despite cautious FXI concentrate usage in the perioperative period.
      CONCLUSIONS: FXI concentrate use is efficacious and safe in the majority of cases
      although physicians should remain mindful of the possibility of thrombotic
      complications.

PMID- 25855342
TI  - Pharmacokinetics, Pharmacodynamics, and Safety of Luseogliflozin in Japanese
      Patients with Type 2 Diabetes Mellitus: A Randomized, Single-blind, Placebo
      controlled Trial.
AB  - INTRODUCTION: Luseogliflozin, a potent, selective sodium glucose cotransporter 2
      inhibitor, promotes urinary glucose excretion (UGE) and reduces plasma glucose
      concentrations. Luseogliflozin was approved for use in Japan after favorable
      pharmacokinetic, pharmacodynamic, and safety profiles were reported in healthy
      Japanese subjects and patients with type 2 diabetes mellitus (T2DM) in clinical
      development studies. We aimed to investigate the pharmacokinetics,
      pharmacodynamics, and safety of multiple doses of luseogliflozin administered
      once daily for 7 days in Japanese patients with T2DM. METHODS: We conducted a
      randomized, placebo-controlled, single-blind, parallel-group, clinical
      pharmacology study at the P-One Clinic, Keikokai Medical Corporation (Tokyo,
      Japan) between August 2009 and November 2009. Forty Japanese patients with T2DM
      were randomly assigned to receive once-daily 0.5, 1, 2.5 or 5 mg luseogliflozin
      or placebo for 7 days. We assessed the pharmacokinetics, pharmacodynamics
      (including changes in UGE and plasma glucose concentrations), and safety of
      luseogliflozin. RESULTS: The plasma concentrations of luseogliflozin and its
      active metabolite, M2, were dose proportional, without accumulation. 24-h UGE was
      greater in all luseogliflozin groups versus placebo. Least-squares mean
      differences in 24-h UGE on Day 7 increased dose dependently in the luseogliflozin
      groups, with values of 49.2, 66.5, 89.4, and 101 g/day at 0.5, 1, 2.5, and 5 mg,
      respectively. On Day 7, the areas under the concentration-time curves for post
      meal plasma glucose and the mean plasma glucose for 0-16 h were significantly
      lower in all luseogliflozin groups versus placebo. Seven patients had mild
      adverse events (AEs); all were resolved. No AEs led to study discontinuation.
      CONCLUSION: Once-daily administration of luseogliflozin for 7 days increased 24-h
      UGE in a dose-dependent manner, reduced plasma glucose concentrations, and was
      well tolerated in Japanese patients with T2DM. The pharmacokinetic and
      pharmacodynamic profile of luseogliflozin observed in this study supports its
      once-daily dosing regimen. FUNDING: Taisho Pharmaceutical Co., Ltd.

PMID- 25855343
TI  - Comparison of real-time PCR methods for the detection of Naegleria fowleri in
      surface water and sediment.
AB  - Naegleria fowleri is a thermophilic free-living ameba found in freshwater
      environments worldwide. It is the cause of a rare but potentially fatal disease
      in humans known as primary amebic meningoencephalitis. Established N. fowleri
      detection methods rely on conventional culture techniques and morphological
      examination followed by molecular testing. Multiple alternative real-time PCR
      assays have been published for rapid detection of Naegleria spp. and N. fowleri.
      Foursuch assays were evaluated for the detection of N. fowleri from surface water
      and sediment. The assays were compared for thermodynamic stability, analytical
      sensitivity and specificity, detection limits, humic acid inhibition effects, and
      performance with seeded environmental matrices. Twenty-one ameba isolates were
      included in the DNA panel used for analytical sensitivity and specificity
      analyses. N. fowleri genotypes I and III were used for method performance
      testing. Two of the real-time PCR assays were determined to yield similar
      performance data for specificity and sensitivity for detecting N. fowleri in
      environmental matrices. 

PMID- 25855344
TI  - Fine structure of the copulatory apparatus of the tapeworm Tetrabothrius erostris
      (Cestoda: Tetrabothriidea).
AB  - The organization and fine structure of the complex copulatory apparatus of
      Tetrabothrius erostris (Tetrabothriidea) is investigated by light and
      transmission electron microscopy. A diversity of microstructures was found on the
      surface of genital ducts. The apical surfaces of male gonadoducts possess tubular
      and blade-like microtriches that have specific structure in each section of the
      duct. The apical part of the tubular microtriches contains numerous constrictions
      in the proximal section of the sperm duct; blade-like microtriches of cirrus
      possess longitudinal striation in the apical part, and their basal part is
      reinforced with electron-dense strands. Two types of microtriches occur on the
      surface of cirrus, and their presence may be considered as systematic features.
      Prostate glands containing granules of medium electron density (up to 130 nm
      diameter) are localized in the cirrus sac. The genital atrium contains numerous
      non-ciliated receptors. Paramyosin-like fibers (up to 200 nm) were found in the
      muscle fibers surrounding the male atrium canal. Microtriches on the surface of
      the distal region of the male atrial canal are covered by a glycocalyx. Electron
      dense, membrane-like structures (up to 40 nm) lie under the apical membrane of
      the genital atrium and vagina. These structures do not form a continuous layer;
      its edges turn down and sink into the apical invaginations of epithelium.
      Hypotheses on the possible ways of copulation in T. erostris based on the
      observed ultrastructure are discussed.

PMID- 25855345
TI  - Exosome-like vesicles derived by Schistosoma japonicum adult worms mediates M1
      type immune- activity of macrophage.
AB  - Exosomes are 30-100-nm membrane vesicles of endocytic origin that are released
      into the extracellular space upon fusion of the multi-vesicular bodies (MVB) with
      the plasma membrane, while initial studies described that the role of exosomes
      was a reticulocyte cargo-disposal mechanism allowing remodeling of the plasma
      membrane during the maturation of reticulocytes to erythrocytes. Recent studies
      indicate that exosomes are secreted by most cells and pathogens and play an
      important role in intercellular signaling and exert regulatory function by
      carrying bioactive molecules. As numerous pathogens, adult worm of Schistosoma
      japonicum (S. japonicum) reside in mesenteric veins of definitive host including
      man and mammal animals. It was reported that the worms or the eggs also have
      specialized secretion systems to export effector proteins or other molecules into
      host target cells. However, the mechanisms involved remained unclear. This study
      investigated the isolation of the exosome-like vesicles secreted by S. japonicum
      adult worms and its immune activity on microphage in vitro. In this report, we
      identified exosome-based secretion as a new mechanism for protein secretion by S.
      japonicum. Electron microscopy tomography revealed the previously unidentified
      ultrastructural detail of exosome-like vesicles with high resolution; they were
      found to be typical spherical shape and to have a diverse population that varies
      in size of 30-100 nm. Exosome-like vesicles isolated from S. japonicum contained
      a significantly different protein compared with debris pelleted and the apoptosis
      body. We also demonstrate that macrophages were preferentially differentiated
      into the M1 subtype while being treated with S. japonicum exosome-like vesicles.
      This study reveals there are exosome-like vesicles derived by S. japonicum adult
      worms, and the exosome-like vesicles can mediate M1-type immune- activity of
      macrophage. 

PMID- 25855346
TI  - Effects of temperature and salinity on the life cycle of Neobenedenia sp.
      (Monogenea: Capsalidae) infecting farmed barramundi (Lates calcarifer).
AB  - Effective parasite management can be achieved through strategically timed
      treatments that break the life cycle. We examined the effects of temperature (2 
      degrees C increments from 22 to 34  degrees C) and salinity (0, 11, 22, 35,
      400/00) on the life cycle (embryonation period, hatching success, oncomiracidia
      (larvae) longevity, infection success, and time to sexual maturity) of
      Neobenedenia sp. (Monogenea: Capsalidae), a harmful ectoparasite of farmed marine
      fishes. Experiments were conducted in controlled conditions in the laboratory.
      The life cycle was faster in warm, high saline conditions compared to cooler
      conditions (10-13 days between 26-32  degrees C, 400/00; 15-16 days between 22-24
      degrees C at 400/00). Warm seawater and high saline conditions (24-32  degrees
      C, 35-400/00) improved egg hatching success, reduced time to sexual maturity, and
      resulted in parasites reaching sexual maturity at a larger size (at 30-32 
      degrees C) compared to cooler conditions (22  degrees C). In contrast, cool,
      hypersaline conditions (22  degrees C, 400/00) increased oncomiracidia longevity
      and infection success. Linear and quantile regression models were used to
      construct an interactive, online parasite management interface to enable
      strategic treatment of parasites in aquaculture corresponding to observed
      temperature and salinity variation on farms in the tropics. It was recommended
      that farmers treat their stock more frequently during summer (27-31  degrees C)
      when parasites can complete their life cycle more quickly. Nevertheless, farmers
      should be aware of the potential for increased Neobenedenia sp. infections during
      winter months (21-26  degrees C) due to increased infection success.

PMID- 25855347
TI  - Molecular and morphological characterization of Haemoproteus (Parahaemoproteus)
      ptilotis, a parasite infecting Australian honeyeaters (Meliphagidae), with
      remarks on prevalence and potential cryptic speciation.
AB  - Avian Haemoproteus (Haemosporida) parasites occur in birds on all continents
      apart from Antarctica. Molecular screening techniques have uncovered previously
      unforeseen levels of Haemoproteus lineage diversity; however, fewer than 20% of
      genetic parasite lineages have been linked to morphological descriptions. The
      process of linking morphological descriptions to DNA barcodes for Haemoproteus
      spp. is important for the study of host-parasite interactions and the potential
      for cryptic speciation. Here, we describe cytochrome-b barcodes and morphological
      diagnostics for the identification of Haemoproteus (Parahaemoproteus) ptilotis, a
      systematically confusing parasite found in Australian honeyeaters (family
      Meliphagidae). We characterised infections from the original type host
      (Lichenostomus chrysops; Family Meliphagidae) as well as from four co-occurring
      meliphagid species in southeast Queensland, Australia, to investigate
      intraspecific variation in morphology and lineage identity. We recorded eight
      lineages that grouped into a well-supported monophyletic group, supporting the
      linkage of the described lineages to H. ptilotis. However, comparisons of
      diagnostics between the type host and co-occurring meliphagid hosts revealed high
      genetic diversity and variable morphology that could be indicative of cryptic
      speciation. This study highlights that morphological descriptions alongside
      molecular characterisation remain crucial if we are to gain an understanding of
      the true diversity and host specificity of protozoan parasites in Australia and
      elsewhere.

PMID- 25855349
TI  - Re-description of Myxobolus fahmii from the gills of Barbus bynni with new data
      on the precise infection site, histological impacts, and seasonality.
AB  - Originally, Myxobolus fahmii was described from the gills of Barbus bynni
      collected from the Nile River, Egypt. The original study provided only mensural
      characteristics of the spores and referred to gill lamellae as the site for the
      infection. In this study, B. bynni were collected from almost the same locality,
      with a similar parasite being found. Our investigations enabled us to determine
      the precise infection site, which corresponded with the "filamental vascular
      type" and to provide, for the first time, information on pathogenicity and on the
      seasonal variation in the prevalence of M. fahmii in gills. The infection was
      recorded as whitish ellipsoidal plasmodia within the afferent artery of the gill
      filaments. Due to continuous growth of the plasmodia, gill lamellae were
      atrophied and obliterated at the plasmodium site. Spores were drop to ovoid
      shaped with a mean length of 11 MUm and mean width of 8 MUm. Polar capsules were
      pear shaped, measuring 7 MUm in length * 3.0 MUm, with 5-7 filament coils. The
      overall prevalence of infection was 32.9% (79/240). The highest prevalence was in
      autumn 63.3% (38/60) while the lowest was in winter 6.6% (4/60). The infection
      showed a significant difference in prevalence between all the seasons except
      autumn and spring and summer and winter.

PMID- 25855348
TI  - Philometra mirabilis sp. n. (Nematoda: Philometridae), a new gonad-infecting
      parasite from the freshwater fish Cichla mirianae (Cichlidae) in Brazilian
      Amazon.
AB  - A new nematode species, Philometra mirabilis sp. n. (Philometridae), is described
      based on a subgravid female specimen recovered from the ovary of the freshwater
      perciform fish Cichla mirianae Kullander and Ferreira (Cichlidae) in the Juruena
      River (Amazon River basin), State of Mato Grosso, Brazil. The new species is
      morphologically very different from congeners parasitizing fishes in South
      America, being mainly characterized by the markedly elongate, narrow body 171 mm
      long (maximum width/body length 1:598), the presence of three small cone-shaped
      oesophageal teeth protruding out of the mouth and an onion-shaped oesophageal
      inflation distinctly separated from the posterior part of the oesophagus, the
      relative length of the oesophagus, and the rounded posterior end of the body
      without any caudal projections. It is the third known valid species of Philometra
      Costa, 1845 parasitizing a freshwater fish in South America and the second
      species of this genus reported from fishes of the family Cichlidae. 

PMID- 25855350
TI  - Factors affecting the anthelmintic efficacy of papaya latex in vivo: host sex and
      intensity of infection.
AB  - The development of plant-derived cysteine proteinases, such as those in papaya
      latex, as novel anthelmintics requires that the variables affecting efficacy be
      fully evaluated. Here, we conducted two experiments, the first to test for any
      effect of host sex and the second to determine whether the intensity of the worm
      burden carried by mice would influence efficacy. In both experiments, we used the
      standard C3H mouse reference strain in which papaya latex supernatant (PLS)
      consistently shows >80 % reduction in Heligmosomoides bakeri worm burdens, but to
      broaden the perspective, we also included for comparison mice of other strains
      that are known to respond more poorly to treatment with papaya latex. Our results
      confirmed that there is a strong genetic influence affecting efficacy of PLS in
      removing adult worm burdens. However, there was no effect of host sex on efficacy
      (C3H and NIH) and no effect of infection intensity (C3H and BALB/c). These
      results offer optimism that plant-derived cysteine proteinases (CPs), such as
      these from papaya latex, can function as effective anthelmintics, with neither
      host sex nor infection intensity presenting further hurdles to impede their
      development for future medicinal and veterinary usage. 

PMID- 25855351
TI  - Laboratory development of permethrin resistance and cross-resistance pattern of
      Culex quinquefasciatus to other insecticides.
AB  - Resistance of mosquitoes to insecticides is a growing concern in India. Since
      only a few insecticides are used for public health and limited development of new
      molecules is expected in the next decade, maintaining the efficacy of control
      programs mostly relies on resistance management strategies. Developing such
      strategies requires a deep understanding of factors influencing resistance
      together with characterizing the mechanisms involved. Among factors likely to
      influence insecticide resistance in mosquitoes, agriculture and urbanization have
      been implicated but rarely studied in detail. In the present study, we evaluate
      the permethrin resistance and cross-resistance pattern of several insecticides in
      Culex quinquefasciatus mosquitoes. After 10 generation of selection with
      permethrin, the LC50 value for both larvae and adult Cx. quinquefasciatus was
      increased by 17.3- and 17.1-folds compared with susceptible strain.
      Detoxification enzyme profiles and native PAGE electrophoresis of esterase
      isoenzyme further revealed that esterase and CytP450 may be involved in
      permethrin resistance (PerRes) strain compared with susceptible strain. In
      addition to cross-resistance, study revealed that high resistance to cypermethrin
      (RR = 6.3, 8.8-folds). This study provided important information for
      understanding permethrin resistance and facilitating a better strategy for the
      management of resistance. These studies conclude that a strong foundation for
      further study of permethrin resistance mechanisms observed in Cx.
      quinquefasciatus mosquitoes. 

PMID- 25855352
TI  - An entropy-like index of bifurcational robustness for metabolic systems.
AB  - Natural and synthetic metabolic pathways need to retain stability when faced
      against random changes in gene expression levels and kinetic parameters. In the
      presence of large parameter changes, a robust system should specifically avoid
      moving to an unstable region, an event that would dramatically change system
      behavior. Here we present an entropy-like index, denoted as S, for quantifying
      the bifurcational robustness of metabolic systems against loss of stability. We
      show that S enables the optimization of a metabolic model with respect to both
      bifurcational robustness and experimental data. We then demonstrate how the
      coupling of ensemble modeling and S enables us to discriminate alternative
      designs of a synthetic pathway according to bifurcational robustness. Finally, we
      show that S enables the identification of a key enzyme contributing to the
      bifurcational robustness of yeast glycolysis. The different applications of S
      demonstrated illustrate the versatile role it can play in constructing better
      metabolic models and designing functional non-native pathways. 

PMID- 25855353
TI  - DNA-Mediated Cyclic GMP-AMP Synthase-Dependent and -Independent Regulation of
      Innate Immune Responses.
AB  - Cytoplasmic DNA activates cyclic GMP-AMP synthase (cGAS) to produce cyclic 2'
      5'3'-5'GMP-AMP dinucleotide (2'5 'cGAMP). The binding of 2'5'cGAMP to an adaptor
      protein, stimulator of IFN genes (STING), activates a transcription factor, IFN
      regulatory factor 3, leading to the induction of IFN and chemokine gene
      expression. In this study, we found that the 2'5'cGAMP-dependent STING activation
      induced highly upregulated CXCL10 gene expression. Formation of a distinct STING
      dimer, which was detected by native PAGE, was induced by 2'5'cGAMP, but not 3'
      5'3'-5'cGAMP. Analysis of DNase II(-/-) mice, which constitutively produce IFN
      beta and CXCL10, showed the accumulation of 2'5'cGAMP in their fetal livers and
      spleens, suggesting that the undigested DNA accumulating in DNase II(-/-) cells
      may have leaked from the lysosomes into the cytoplasm. The DNase II(-/-) mouse
      embryonic fibroblasts produced 2'5'cGAMP in a cGAS-dependent manner during
      apoptotic cell engulfment. However, cGAS deficiency did not impair the STING
      dependent upregulation of CXCL10 in DNase II(-/-) mouse embryonic fibroblasts
      that was induced by apoptotic cell engulfment or DNA lipofection. These results
      suggest the involvement of a cGAS-independent additional DNA sensor(s) that
      induces the STING-dependent activation of innate immunity. 

PMID- 25855354
TI  - An NK Cell Population Lacking FcRgamma Is Expanded in Chronically Infected HIV
      Patients.
AB  - We previously demonstrated that NK cells from HIV-infected individuals have
      elevated expression of activation markers, spontaneously degranulate ex vivo, and
      decrease expression of a signal-transducing protein for NK-activating receptors,
      FcRgamma. Importantly, these changes were maintained in virologically suppressed
      (VS) individuals receiving combination antiretroviral therapy (cART). In this
      study, we show that loss of FcRgamma is caused by the expansion of a novel subset
      of FcRgamma(-)CD56(dim) NK cells with an altered activation receptor repertoire
      and biological properties. In a cross-sectional study, FcRgamma(-) NK cells as a
      proportion of total CD56(dim) NK cells increased in cART-naive viremic HIV
      infected individuals (median [interquartile range] = 25.9 [12.6-56.1] compared
      with 3.80 [1.15-11.5] for HIV(-) controls, p < 0.0001) and in VS HIV-infected
      individuals (22.7 [13.1-56.2] compared with 3.80 [1.15-11.5], p = 0.0004), with
      no difference between cART-naive and VS patients (p = 0.93). FcRgamma(-) NK cells
      expressed no NKp30 or NKp46. They showed greater Ab-dependent cellular
      cytotoxicity activity against rituximab-opsonized Raji cells and in a whole-blood
      assay measuring NK responses to overlapping HIV peptides, despite having reduced
      CD16 expression compared with conventional NK cells. Their prevalence correlated
      with CMV Ab titers in HIV(-) subjects but not in HIV(+) individuals, and with the
      inflammatory marker CXCL10 in both groups. The expansion of a subset of NK cells
      that lacks NKp30 and NKp46 to ~90% of CD56(dim) NK cells in some VS HIV(+)
      individuals may influence NK-mediated immunosurveillance in patients receiving
      cART. 

PMID- 25855355
TI  - Factor H-related protein 5 interacts with pentraxin 3 and the extracellular
      matrix and modulates complement activation.
AB  - The physiological roles of the factor H (FH)-related proteins are controversial
      and poorly understood. Based on genetic studies, FH-related protein 5 (CFHR5) is
      implicated in glomerular diseases, such as atypical hemolytic uremic syndrome,
      dense deposit disease, and CFHR5 nephropathy. CFHR5 was also identified in
      glomerular immune deposits at the protein level. For CFHR5, weak complement
      regulatory activity and competition for C3b binding with the plasma complement
      inhibitor FH have been reported, but its function remains elusive. In this study,
      we identify pentraxin 3 (PTX3) as a novel ligand of CFHR5. Binding of native
      CFHR5 to PTX3 was detected in human plasma and the interaction was characterized
      using recombinant proteins. The binding of PTX3 to CFHR5 is of ~2-fold higher
      affinity compared with that of FH. CFHR5 dose-dependently inhibited FH binding to
      PTX3 and also to the monomeric, denatured form of the short pentraxin C-reactive
      protein. Binding of PTX3 to CFHR5 resulted in increased C1q binding.
      Additionally, CFHR5 bound to extracellular matrix in vitro in a dose-dependent
      manner and competed with FH for binding. Altogether, CFHR5 reduced FH binding and
      its cofactor activity on pentraxins and the extracellular matrix, while at the
      same time allowed for enhanced C1q binding. Furthermore, CFHR5 allowed formation
      of the alternative pathway C3 convertase and supported complement activation.
      Thus, CFHR5 may locally enhance complement activation via interference with the
      complement-inhibiting function of FH, by enhancement of C1q binding, and by
      activating complement, thereby contributing to glomerular disease. 

PMID- 25855356
TI  - Impaired NK Cell Responses to Pertussis and H1N1 Influenza Vaccine Antigens in
      Human Cytomegalovirus-Infected Individuals.
AB  - NK cells contribute to postvaccination immune responses after activation by IL-2
      from Ag-specific memory T cells or by cross-linking of the low-affinity IgG
      receptor, CD16, by Ag-Ab immune complexes. Sensitivity of NK cells to these
      signals from the adaptive immune system is heterogeneous and influenced by their
      stage of differentiation. CD56(dim)CD57(+) NK cells are less responsive to IL-2
      and produce less IFN-gamma in response to T cell-mediated activation than do
      CD56(bright) or CD56(dim)CD57(-) NK cells. Conversely, NK cell cytotoxicity, as
      measured by degranulation, is maintained across the CD56(dim) subsets. Human CMV
      (HCMV), a highly prevalent herpes virus causing lifelong, usually latent,
      infections, drives the expansion of the CD56(dim)CD57(+)NKG2C(+) NK cell
      population, skewing the NK cell repertoire in favor of cytotoxic responses at the
      expense of cytokine-driven responses. We hypothesized, therefore, that HCMV
      seropositivity would be associated with altered NK cell responses to vaccine Ags.
      In a cross-sectional study of 152 U.K. adults, with HCMV seroprevalence rate of
      36%, we find that HCMV seropositivity is associated with lower NK cell IFN-gamma
      production and degranulation after in vitro restimulation with pertussis or H1N1
      influenza vaccine Ags. Higher expression of CD57/NKG2C and lower expression of IL
      18Ralpha on NK cells from HCMV seropositive subjects do not fully explain these
      impaired responses, which are likely the result of multiple receptor-ligand
      interactions. This study demonstrates for the first time, to our knowledge, that
      HCMV serostatus influences NK cell contributions to adaptive immunity and raises
      important questions regarding the impact of HCMV infection on vaccine efficacy. 

PMID- 25855357
TI  - Cutting Edge: Differential Regulation of PTEN by TCR, Akt, and FoxO1 Controls
      CD4+ T Cell Fate Decisions.
AB  - Signaling via the Akt/mammalian target of rapamycin pathway influences CD4(+) T
      cell differentiation; low levels favor regulatory T cell induction and high
      levels favor Th induction. Although the lipid phosphatase phosphatase and tensin
      homolog (PTEN) suppresses Akt activity, the control of PTEN activity is poorly
      studied in T cells. In this study, we identify multiple mechanisms that regulate
      PTEN expression. During Th induction, PTEN function is suppressed via lower mRNA
      levels, lower protein levels, and an increase in C-terminal phosphorylation.
      Conversely, during regulatory T cell induction, PTEN function is maintained
      through the stabilization of PTEN mRNA transcription and sustained protein
      levels. We demonstrate that differential Akt/mammalian target of rapamycin
      signaling regulates PTEN transcription via the FoxO1 transcription factor. A
      mathematical model that includes multiple modes of PTEN regulation recapitulates
      our experimental findings and demonstrates how several feedback loops determine
      differentiation outcomes. Collectively, this work provides novel mechanistic
      insights into how differential regulation of PTEN controls alternate CD4(+) T
      cell fate outcomes. 

PMID- 25855358
TI  - T Cell Cross-Reactivity between a Highly Immunogenic EBV Epitope and a Self
      Peptide Naturally Presented by HLA-B*18:01+ Cells.
AB  - T cell cross-reactivity underpins the molecular mimicry hypothesis in which
      microbial peptides sharing structural features with host peptides stimulate T
      cells that cross-react with self-peptides, thereby initiating and/or perpetuating
      autoimmune disease. EBV represents a potentially important factor in the
      pathogenesis of several T cell-mediated autoimmune disorders, with molecular
      mimicry a likely mechanism. In this study, we describe a human self-peptide
      (DELEIKAY) that is a homolog of a highly immunogenic EBV T cell epitope
      (SELEIKRY) presented by HLA-B*18:01. This self-peptide was shown to bind stably
      to HLA-B*18:01, and peptide elution/mass spectrometric studies showed it is
      naturally presented by this HLA molecule on the surface of human cells. A
      significant proportion of CD8(+) T cells raised from some healthy individuals
      against this EBV epitope cross-reacted with the self-peptide. A diverse array of
      TCRs was expressed by the cross-reactive T cells, with variable functional
      avidity for the self-peptide, including some T cells that appeared to avoid
      autoreactivity by a narrow margin, with only 10-fold more of the self-peptide
      required for equivalent activation as compared with the EBV peptide. Structural
      studies revealed that the self-peptide-HLA-B*18:01 complex is a structural mimic
      of the EBV peptide-HLA-B*18:01 complex, and that the strong antiviral T cell
      response is primarily dependent on the alanine/arginine mismatch at position 7.
      To our knowledge, this is the first report confirming the natural presentation of
      a self-peptide cross-recognized in the context of self-HLA by EBV-reactive CD8(+)
      T cells. These results illustrate how aberrant immune responses and
      immunopathological diseases could be generated by EBV infection. 

PMID- 25855359
TI  - Dimethylaminopyridine-supported graft polymer catalyst and its flow system.
AB  - A new heterogeneous organocatalyst, graft polymer supported dimethylaminopyridine
      (g-DMAP), is developed. This catalyst has a flexible structure and comprises DMAP
      anchored to the polyethylene-graft-polyacrylic acid (PE-g-PAA). It exhibits
      higher activity than DMAP supported on polystyrene cross-linked with
      divinylbenzene and can be recovered in batch mode acetylation. The activity and
      stability of this catalyst allow its application in continuous flow systems.
      Continuous acetylation proceeds with excellent conversion, and a turnover number
      of 560 can be achieved using g-DMAP. Parallel fixed bed reactors were used to
      scale up the synthesis of this continuous flow system. Eight parallel fixed bed
      reactors displayed excellent conversion. 

PMID- 25855360
TI  - Growing Candida albicans Biofilms on Paper Support and Dynamic Conditions.
AB  - A stainless steel paper-embedded biofilm reactor (PEBR) was developed for Candida
      spp. growth, permitting confluent distribution of nutrients by capillary
      diffusion through ordinary laboratory filter paper. Antibiogram disks were
      distributed along the filter paper rim, and the PEBR received 0.1 or 0.01 %
      crystal violet (CV) at 200 MUL min(-1) and at 37  degrees C, for 48 h. CV was
      recovered from the disks and measured at 540 nm. Candida albicans SC5314 cells
      were applied onto antibiogram disks. The bioreactor was assembled, and YEPD broth
      was admitted (200 MUL min(-1)) at 37  degrees C, for 72 h. Biofilm growth was
      estimated via the MTT reduction test. Controls were disks that received the same
      treatments, except for the fungus. The PEBR was considered high-throughput table,
      low-cost, and feasible to grow C. albicans biofilms.

PMID- 25855362
TI  - An evaluation of the use of immunoglobulin A antibody response against
      mycobacterial antigens for the diagnosis of Mycobacterium bovis infection in
      cattle.
AB  - Antibody responses are useful indicators of Mycobacterium bovis infection in
      cattle. Many studies have evaluated the ability of immunoglobulin G (IgG) to
      serodiagnose bovine tuberculosis (TB). In the current study, immunoglobulin A
      (IgA) and IgG responses against the MPB70 and MPB83 antigens of M. bovis, the 38
      kDa phosphate-binding lipoprotein (PstS1) that is a well-known serodiagnostic M.
      tuberculosis antigen, and a newly identified protein, termed Rv1483c, were
      compared in M. bovis-infected and noninfected cattle as well as in field samples.
      The diagnostic utility of the IgA antibody to MPB70 and MPB83 for bovine TB was
      superior or comparable to that of the IgG antibody, and the sensitivity of
      serodiagnosis increased when the results of antigen binding by IgA and IgG were
      combined. The sensitivities of the IgG and IgA antibodies to the Rv1483c and
      PstS1 proteins were significantly lower than those to MPB70 and MPB83, and no
      diagnostic utility for Rv1483c was observed in field samples. Importantly, the
      IgA antibody reacted strongly to the MPB70 and MPB83 antigens and differentiated
      cattle with TB from healthy cattle in a multiantigen printed immunoassay. The
      results of this study support the feasibility of using IgA antibody against the
      MPB70 and MPB83 antigens to detect bovine TB. In addition, approaches using
      assays for both IgA and IgG antibodies may increase detection accuracy.

PMID- 25855361
TI  - Liraglutide attenuates high glucose-induced abnormal cell migration,
      proliferation, and apoptosis of vascular smooth muscle cells by activating the
      GLP-1 receptor, and inhibiting ERK1/2 and PI3K/Akt signaling pathways.
AB  - BACKGROUND: As a new anti-diabetic medicine, Liraglutide (LIRA), one of GLP-1
      analogues, has been found to have an anti-atherosclerotic effect. Since vascular
      smooth muscle cells (VSMCs) play pivotal roles in the occurrence of diabetic
      atherosclerosis, it is important to investigate the role of LIRA in reducing the
      harmful effects of high-glucose (HG) treatment in cultured VSMCs, and identifying
      associated molecular mechanisms. METHODS: Primary rat VSMCs were exposed to low
      or high glucose-containing medium with or without LIRA. They were challenged with
      HG in the presence of phosphatidylinositol 3-kinase (PI3K), extracellular signal
      regulated kinase (ERK)1/2, or glucagon-like peptide receptor (GLP-1R) inhibitors.
      Cell proliferation and viability was evaluated using a Cell Counting Kit-8. Cell
      migration was determined by Transwell migration and scratch wound assays. Flow
      cytometry and Western blotting were used to determine apoptosis and protein
      expression, respectively. RESULTS: Under the HG treatment, VSMCs exhibited
      increased migration, proliferation, and phosphorylation of protein kinase B (Akt)
      and ERK1/2, along with reduced apoptosis (all p < 0.01 vs. control). These
      effects were significantly attenuated with LIRA co-treatment (all p < 0.05 vs. HG
      alone). Inhibition of PI3K kinase and ERK1/2 similarly attenuated the HG-induced
      effects (all p < 0.01 vs. HG alone). GLP-1R inhibitors effectively reversed the
      beneficial effects of LIRA on HG treatment (all p < 0.05). CONCLUSIONS: HG
      treatment may induce abnormal phenotypes in VSMCs via PI3K and ERK1/2 signaling
      pathways activated by GLP-1R, and LIRA may protect cells from HG damage by acting
      on these same pathways.

PMID- 25855363
TI  - Application of a pathogen microarray for the analysis of viruses and bacteria in
      clinical diagnostic samples from pigs.
AB  - Many of the disease syndromes challenging the commercial swine industry involve
      the analysis of complex problems caused by polymicrobial, emerging or reemerging,
      and transboundary pathogens. This study investigated the utility of the Lawrence
      Livermore Microbial Detection Array (Lawrence Livermore National Laboratory,
      Livermore, California), designed to detect 8,101 species of microbes, in the
      evaluation of known and unknown microbes in serum, oral fluid, and tonsil from
      pigs experimentally coinfected with Porcine reproductive and respiratory syndrome
      virus (PRRSV) and Porcine circovirus-2 (PCV-2). The array easily identified PRRSV
      and PCV-2, but at decreased sensitivities compared to standard polymerase chain
      reaction detection methods. The oral fluid sample was the most informative,
      possessing additional signatures for several swine-associated bacteria, including
      Streptococcus sp., Clostridium sp., and Staphylococcus sp.

PMID- 25855364
TI  - Enhanced detection of Porcine reproductive and respiratory syndrome virus in
      fixed tissues by in situ hybridization following tyramide signal amplification.
AB  - This study evaluated the sensitivity of biotinyl-tyramide-based in situ
      hybridization (TISH) method by comparison with chromogenic in situ hybridization
      (CISH) and immunohistochemical staining (IHC) methods. This study also determined
      the effect of fixative and fixation time on the detection of Porcine reproductive
      and respiratory syndrome virus (PRRSV) in paraffin-embedded tissues. Lung samples
      were fixed in 4% paraformaldehyde (PFA) or 10% neutral buffered formalin (NBF)
      for various times before paraffin embedding. Of 30 paraffin-embedded lung
      samples, fixed for 1 day in 4% PFA or 10% NBF, 18 (60%) were positive for PRRSV
      by nested reverse transcription polymerase chain reaction (nRT-PCR). All 18 lung
      samples (100%) also were positive for PRRSV by TISH, but only 10 of these 18
      specimens (56%) were positive for PRRSV by IHC and CISH. We demonstrated that
      TISH can detect PRRSV RNA in paraffin-embedded tissues after up to 90 days of
      fixation. PRRSV nucleic acids and antigens were better preserved in 4% PFA than
      in 10% NBF. Compared with CISH and IHC testing methods, TISH appeared to be more
      sensitive for the detection of PRRSV in paraffin-embedded tissues.

PMID- 25855366
TI  - Synthesis, characterization, photophysics, and anion binding properties of
      platinum(ii) acetylide complexes with urea group.
AB  - A new class of platinum(ii) acetylide complexes with urea group,
      [Pt((t)Bu3tpy)(C[triple bond, length as m-dash]CC6H4-4-NHC(O)NHC6H4-4-R)](OTf)
      ((t)Bu3tpy = 4,4',4''-tri-tert-butyl-2,2':6',2''-terpyridine; R = H (), Cl (),
      CF3 (), and NO2 ()), has been synthesized and characterized. The crystal
      structures of , .DMF.THF, .CH3CN, and .CH3CN have been determined by X-ray
      diffraction. Upon excitation at lambda > 380 nm, the solid samples of complexes
      show orange light at 298 K. The anion binding properties of complexes have been
      studied by UV-vis titration experiments in CH3CN and DMSO. In general, the log K
      values of with the same anion in CH3CN depend on the substituent R on the
      acetylide ligand of and follow this order: R = NO2 () > CF3 () > Cl () > H ().
      For the same complex with different anions, the log K values are in the following
      order: F(-) > OAc(-) > Cl(-) > Br(-) ~ HSO4(-) ~ NO3(-) > I(-), which is in
      accordance with the decrease in the basicity of anions. Complex with NO2 group
      shows a dramatic colour change towards F(-) in DMSO, allowing the naked eye
      detection of F(-). 

PMID- 25855365
TI  - Development of Aerobic Fitness in Young Team Sport Athletes.
AB  - The importance of a high level of aerobic fitness for team sport players is well
      known. Previous research suggests that aerobic fitness can be effectively
      increased in adults using traditional aerobic conditioning methods, including
      high-intensity interval and moderate-intensity continuous training, or more
      recent game-based conditioning that involves movement and skill-specific tasks,
      e.g. small-sided games. However, aerobic fitness training for youth team sport
      players has received limited attention and is likely to differ from that for
      adults due to changes in maturation. Given young athletes experience different
      rates of maturation and technical skill development, the most appropriate aerobic
      fitness training modes and loading parameters are likely to be specific to the
      developmental stage of a player. Therefore, we analysed studies that investigated
      exercise protocols to enhance aerobic fitness in young athletes, relative to
      growth and maturation, to determine current best practice and limitations.
      Findings were subsequently used to guide an evidence-based model for aerobic
      fitness development. During the sampling stage (exploration of multiple sports),
      regular participation in moderate-intensity aerobic fitness training, integrated
      into sport-specific drills, activities and skill-based games, is recommended.
      During the specialisation stage (increased commitment to a chosen sport), high
      intensity small-sided games should be prioritised to provide the simultaneous
      development of aerobic fitness and technical skills. Once players enter the
      investment stage (pursuit of proficiency in a chosen sport), a combination of
      small-sided games and high-intensity interval training is recommended. 

PMID- 25855367
TI  - Synthesis of Monodispersed Submillimeter-Sized Molecularly Imprinted Particles
      Selective for Human Serum Albumin Using Inverse Suspension Polymerization in
      Water-in-Oil Emulsion Prepared Using Microfluidics.
AB  - We synthesized monodispersed submillimeter-sized (100 MUm-1 mm) microgels by
      inverse suspension polymerization of water-soluble monomer species with a
      photoinitiator in water-in-oil (W/O) droplets formed by the microchannel. After
      fundamental investigations of the selection of suitable surfactants, surfactant
      concentration, and flow rate, we successfully prepared monodispersed
      submillimeter-sized W/O droplets. Because radical polymerization based on thermal
      initiation was not appropriated based on colloidal stability, we selected
      photoinitiation, which resulted in the successful synthesis of monodispersed
      submillimeter-sized microgels with sufficient colloidal stability. The microgel
      size was controlled by the flow rate of the oil phase, which maintained the
      monodispersity. In addition, the submillimeter-sized microgels exhibit high
      affinity and selective binding toward HSA utilizing molecular imprinting. We
      believe the monodispersed submillimeter-sized molecularly imprinted microgels can
      be used as affinity column packing materials without any biomolecules, such as
      antibodies, for sample pretreatment to remove unwanted proteins without a pump
      system. 

PMID- 25855368
TI  - Development of a gas-diffusion microfluidic paper-based analytical device (MUPAD)
      for the determination of ammonia in wastewater samples.
AB  - An inexpensive, disposable and highly selective microfluidic paper-based
      analytical device (MUPAD) is described for the determination of ammonia
      (molecular ammonia and ammonium cation) in wastewaters which implements for the
      first time a gas-diffusion separation step on a paper-based platform. Its
      hydrophilic reagent zones were defined by printing filter paper with a
      hydrophobic paper sizing agent using a conventional inkjet printer. The sample
      was introduced into the sodium hydroxide impregnated sample zone of the MUPAD.
      This allowed the quantitative conversion of the ammonium ion to molecular ammonia
      which diffused across the hydrophobic microporous Teflon membrane of the device
      into an adjacent hydrophilic reagent zone containing the acid-base indicator 3
      nitrophenol or bromothymol blue. The change in indicator color was measured using
      a desktop scanner for ammonia quantification. Under optimal conditions, the MUPAD
      is characterized by a limit of detection of 0.8 and 1.8 mg N L(-1) and
      repeatability of 3.1 and 3.7% (n >= 10, 20 mg N L(-1)), expressed as relative
      standard deviation, in the case of 3-nitrophenol or bromothymol blue,
      respectively. This MUPAD was used successfully for the determination of ammonia
      in sewage and soil water samples. The small dimensions, minimal reagent
      consumption, low cost, simplicity of operation, and possibility of using a
      portable scanner make the proposed MUPAD suitable for on-site ammonia monitoring
      in contaminated environmental waters and domestic, agricultural and industrial
      wastewaters. The successful implementation of the gas-diffusion approach on a
      paper-based platform is expected to result in the development of other MUPADs for
      volatile analytes. 

PMID- 25855371
TI  - Synthesis and evaluation of trehalose-based compounds as novel inhibitors of
      cancer cell migration and invasion.
AB  - As a continuous research for the discovery of trehalose-based anti-invasive
      agents, we developed a convenient synthetic approach for the preparation of 6,6'
      dideoxy-6,6'-bis(acylamino)-alpha,alpha-D-trehaloses. A series of trehalose-based
      amides were prepared through the trityl protection of the two primary hydroxyls
      of alpha,alpha-D-trehalose, benzoylation, the removal of the trityl protective
      group, mesylation, azidation, catalytic hydrogenation in the presence of
      hydrochloride, coupling reaction with a variety of acids, and subsequent
      debenzoylation and deacetylation in some cases. Compound 8b, 6,6'-dideoxy-6,6'
      bis(2-hydroxybenzamide)-alpha,alpha-D-trehalose, was just as potent as the
      natural brartemicin against the invasion of murine colon 26-L5 cells. It
      exhibited no cytotoxicity on human breast adenocarcinoma MDA-MB-231 and murine
      colon 26-L5 cells. It can significantly inhibit the migration and invasion of the
      MDA-MB-231 cells. The anti-invasive effect of 8b was possibly related to its
      inhibitory activity on MMP-9, its suppression on the expression of MMP-9 and
      VEGF, and its deactivation of Akt. 

PMID- 25855370
TI  - Pediatric loss of control eating syndrome: Association with attention
      deficit/hyperactivity disorder and impulsivity.
AB  - OBJECTIVE: Despite data linking Attention-deficit/Hyperactivity Disorder (ADHD)
      and adult binge eating, there are limited data in children with loss of control
      (LOC) eating. We examined inhibitory control in children with LOC eating syndrome
      (LOC-ES) and its association with ADHD. METHOD: 79 children (8-14 years) over the
      fifth weight percentile were recruited, irrespective of LOC eating or ADHD
      status. The Eating Disorder Examination for Children and the Standard Pediatric
      Eating Episode Interview assessed LOC-ES. ADHD diagnosis was determined by the
      Schedule for Affective Disorders and Schizophrenia for children and Conners-3
      (Parent Report) DSM-IV Scales of Inattention and/or Hyperactivity (T score > 65).
      The Go/No-Go (GNG) Task and the Behavior Regulation Inventory of Executive
      Function (BRIEF) assessed impulse control. RESULTS: Odds of LOC-ES were increased
      12 times for children with ADHD (adjusted odds ratio [aOR] = 12.68, 95%
      confidence interval [CI] = 3.11, 51.64, p < 0.001), after adjusting for BMI z
      scores and relevant covariates. Children had 1.17 times higher odds of reporting
      LOC-ES with every 5% increase in GNG Commission Rate (aOR = 1.17, CI = 1.01,
      1.36, p < 0.05) and 1.25 times higher odds of reporting LOC-ES with every 5 unit
      T-score increase in BRIEF Inhibit Scale (aOR = 1.25, CI = 1.04, 1.50, p < 0.05).
      DISCUSSION: Children with ADHD had significantly greater odds of LOC-ES compared
      to children without ADHD. Children with LOC-ES had significantly greater impulse
      control deficits on performance-based neuropsychological assessments and on
      parent reports than children without LOC-ES. These findings suggest a need to
      investigate possible shared mechanisms such as impulse control deficits, among
      children with LOC-ES and ADHD.

PMID- 25855369
TI  - Endovascular strategy or open repair for ruptured abdominal aortic aneurysm: one
      year outcomes from the IMPROVE randomized trial.
AB  - AIMS: To report the longer term outcomes following either a strategy of
      endovascular repair first or open repair of ruptured abdominal aortic aneurysm,
      which are necessary for both patient and clinical decision-making. METHODS AND
      RESULTS: This pragmatic multicentre (29 UK and 1 Canada) trial randomized 613
      patients with a clinical diagnosis of ruptured aneurysm; 316 to an endovascular
      first strategy (if aortic morphology is suitable, open repair if not) and 297 to
      open repair. The principal 1-year outcome was mortality; secondary outcomes were
      re-interventions, hospital discharge, health-related quality-of-life (QoL) (EQ
      5D), costs, Quality-Adjusted-Life-Years (QALYs), and cost-effectiveness
      [incremental net benefit (INB)]. At 1 year, all-cause mortality was 41.1% for the
      endovascular strategy group and 45.1% for the open repair group, odds ratio 0.85
      [95% confidence interval (CI) 0.62, 1.17], P = 0.325, with similar re
      intervention rates in each group. The endovascular strategy group and open repair
      groups had average total hospital stays of 17 and 26 days, respectively, P <
      0.001. Patients surviving rupture had higher average EQ-5D utility scores in the
      endovascular strategy vs. open repair groups, mean differences 0.087 (95% CI
      0.017, 0.158), 0.068 (95% CI -0.004, 0.140) at 3 and 12 months, respectively.
      There were indications that QALYs were higher and costs lower for the
      endovascular first strategy, combining to give an INB of L3877 (95% CI L253,
      L7408) or ?4356 (95% CI ?284, ?8323). CONCLUSION: An endovascular first strategy
      for management of ruptured aneurysms does not offer a survival benefit over 1
      year but offers patients faster discharge with better QoL and is cost-effective.
      CLINICAL TRIAL REGISTRATION: ISRCTN 48334791.

PMID- 25855372
TI  - Biochemical Comparison of Commercial Selenium Yeast Preparations.
AB  - The trace mineral selenium (Se) is an essential element for human and animal
      nutrition. The addition of Se to the diet through dietary supplements or
      fortified food/feed is increasingly common owing to the often sub-optimal content
      of standard diets of many countries. Se supplements commercially available
      include the inorganic mineral salts such as sodium selenite or selenate, and
      organic forms such as Se-enriched yeast. Today, Se yeast is produced by several
      manufacturers and has become the most widely used source of Se for human
      supplementation and is also widely employed in animal nutrition where approval in
      all species has been granted by regulatory bodies such as the European Food
      Safety Authority (EFSA). Characterisation and comparison of Se-enriched yeast
      products has traditionally been made by quantifying total selenomethionine
      (SeMet) content. A disadvantage of this approach, however, is that it does not
      consider the effects of Se deposition on subsequent digestive availability. In
      this study, an assessment was made of the water-soluble extracts of commercially
      available Se-enriched yeast samples for free, peptide-bound and total water
      soluble SeMet. Using LC-MS/MS, a total of 62 Se-containing proteins were
      identified across four Se yeast products, displaying quantitative/qualitative
      changes in abundance relative to the certified reference material, SELM-1 (P
      value <0.05; fold change >=2). Overall, the study indicates that significant
      differences exist between Se yeast products in terms of SeMet content, Se
      containing protein abundance and associated metabolic pathways. 

PMID- 25855373
TI  - Concentration of Selected Metals in Whole Blood, Plasma, and Urine in Short
      Stature and Healthy Children.
AB  - The short stature in children is defined as height below the third percentile
      from the mean for age and gender. This problem affects about 3% of young people.
      More than 20,000 children in Poland have problems with short stature. There is
      not much information available in the literature on the study of metals in blood,
      plasma, and urine in children with short stature. The study was conducted on a
      group of 56 short stature Polish children and 35 healthy children. The content of
      metals was determined using high-performance ion chromatography and inductively
      coupled plasma mass spectrometry methods. The study revealed significant
      differences between the content of selected metals in body fluids between a short
      stature group and healthy children. There were significant differences in the Fe,
      Cu, and Ni concentrations between the groups with respect to the hormonal
      therapy. There were no significant differences between the groups with respect to
      the area where the children lived. The results showed no statistically
      significant differences between metal concentration and age, body weight, and
      height. The study demonstrated statistically significant differences between the
      content of metals in body fluids in short stature children compared with the
      healthy children. It seems that the difference in the concentration of certain
      elements may also be the result of growth hormone therapy and the interaction
      between various metals. Both the alterations in the content of metals and their
      mutual interactions may play an important role in the pathogenesis of short
      stature children.

PMID- 25855374
TI  - Role of Exogenous Melatonin on Cell Proliferation and Oxidant/Antioxidant System
      in Aluminum-Induced Renal Toxicity.
AB  - Aluminum has toxic potential on humans and animals when it accumulates in various
      tissues. It was shown in a number of studies that aluminum causes oxidative
      stress by free radical formation and lipid peroxidation in tissues and thus may
      cause damage in target organs. Although there are numerous studies investigating
      aluminum toxicity, biochemical mechanisms of the damage caused by aluminum have
      yet to be explained. Melatonin produced by pineal gland was shown to be an
      effective antioxidant. Since kidneys are target organs for aluminum accumulation
      and toxicity, we have studied the role of melatonin against aluminum-induced
      renal toxicity in rats. Wistar albino rats were divided into five groups. Group I
      served as control, and received only physiological saline; group II served as
      positive control for melatonin, and received ethanol and physiological saline;
      group III received melatonin (10 mg/kg); group IV received aluminum sulfate (5
      mg/kg) and group V received aluminum sulfate and melatonin (in the same dose),
      injected three times a week for 1 month. Administration of aluminum caused
      degenerative changes in renal tissues, such as increase in metallothionein
      immunoreactivity and decrease in cell proliferation. Moreover, uric acid and
      lipid peroxidation levels and xanthine oxidase activity increased, while
      glutathione, catalase, superoxide dismutase, paraoxonase 1, glucose-6-phosphate
      dehydrogenase, and sodium potassium ATPase activities decreased. Administration
      of melatonin mostly prevented these symptoms. Results showed that melatonin is a
      potential beneficial agent for reducing damage in aluminum-induced renal
      toxicity. 

PMID- 25855375
TI  - Alterations of Functional Connectivity Among Resting-State Networks in
      Hypothyroidism.
AB  - Hypothyroidism affects brain functioning as suggested by various neuroimaging
      studies. The primary focus of the present study was to examine whether
      hypothyroidism would impact connectivity among resting-state networks (RSNs)
      using resting-state functional magnetic resonance imaging (rsfMRI). Twenty-two
      patients with hypothyroidism and 22 healthy controls were recruited and scanned
      using rsfMRI. The data were analysed using independent component analysis and a
      dual regression approach that was applied on five RSNs that were identified using
      fsl software (http://fsl.fmrib.ox.ac.uk). Hypothyroid patients showed
      significantly decreased functional connectivity in the regions of the right
      frontoparietal network (frontal pole), the medial visual network (lateral
      occipital gyrus, precuneus cortex and cuneus) and the motor network (precentral
      gyrus, postcentral gyrus, precuneus cortex, paracingulate gyrus, cingulate gyrus
      and supramarginal gyrus) compared to healthy controls. The reduced functional
      connectivity in the right frontoparietal network, the medial visual network and
      the motor network suggests neurocognitive alterations in hypothyroid patients in
      the corresponding functions. However, the study would be further continued to
      investigate the effects of thyroxine treatment and correlation with
      neurocognitive scores. The findings of the present study provide further
      interesting insights into our understanding of the action of thyroid hormone on
      the adult human brain. 

PMID- 25855376
TI  - Benefits of prophylaxis versus on-demand treatment in adolescents and adults with
      severe haemophilia A: the POTTER study.
AB  - Rigorous evidence is lacking on long-term outcomes of factor VIII (FVIII)
      prophylaxis initiated in adolescent or adult patients with severe haemophilia A.
      The prospective, open-label Prophylaxis versus On-demand Therapy Through Economic
      Report (POTTER) study (ClinicalTrials.gov NCT01159587) compared long-term late
      secondary prophylaxis (recombinant FVIII-FS 20-30 IU/kg thrice weekly) with on
      demand treatment in patients aged 12 to 55 years with severe haemophilia A. The
      annual number of joint bleeding episodes (primary endpoint), total bleeding
      episodes, orthopaedic and radiologic (Pettersson) scores, health-related quality
      of life (HRQoL), pharmacoeconomic impact, and safety were evaluated over a > 5
      year period (2004-2010). Fifty-eight patients were enrolled at 11 centres in
      Italy; 53 (27 prophylaxis, 26 on demand) were evaluated and stratified into 2 age
      subgroups (12-25 and 26-55 years). Patients receiving prophylaxis experienced a
      significantly lower number of joint bleeding episodes vs the on-demand group
      (annualised bleeding rate, 1.97 vs 16.80 and 2.46 vs 16.71 in younger and older
      patients, respectively; p=0.0043). Results were similar for total bleeding
      episodes. Prophylaxis was associated with significantly fewer target joints (p<
      0.001), better orthopaedic (p=0.0019) and Pettersson (p=0.0177) scores, better
      HRQoL, and fewer days of everyday activities lost (p< 0.0001) but required
      significantly higher FVIII product consumption. The POTTER study is the first
      prospective, controlled trial documenting long-term benefits of late secondary
      prophylaxis in adolescents and adults with severe haemophilia A. The benefits of
      reduced bleeding frequency, improved joint status, and HRQoL may offset the
      higher FVIII consumption and costs. 

PMID- 25855377
TI  - Decreased ferroportin promotes myeloma cell growth and osteoclast
      differentiation.
AB  - Iron homeostasis is disrupted in multiple myeloma, a difficult-to-cure plasma
      cell malignancy with lytic bone lesions. Here, we systematically analyzed iron
      gene expression signature and demonstrated that mRNA expression of iron exporter
      ferroportin (FPN1) is significantly downregulated in myeloma cells and correlates
      negatively with clinic outcome. Restoring expression of FPN1 reduces
      intracellular liable iron pool, inhibits STAT3-MCL-1 signaling, and suppresses
      myeloma cells growth. Furthermore, we demonstrated that mRNA of FPN1 is also
      downregulated at the initial stages of osteoclast differentiation and suppresses
      myeloma cell-induced osteoclast differentiation through regulating iron regulator
      TFRC, NF-kappaB, and JNK pathways. Altogether, we demonstrated that
      downregulation of FPN1 plays critical roles in promoting myeloma cell growth and
      bone resorption in multiple myeloma.

PMID- 25855379
TI  - Amino Acid transporters in cancer and their relevance to "glutamine addiction":
      novel targets for the design of a new class of anticancer drugs.
AB  - Tumor cells have an increased demand for amino acids because of their rapid
      proliferation rate. In addition to their need in protein synthesis, several amino
      acids have other roles in supporting cancer growth. There are approximately two
      dozen amino acid transporters in humans, and tumor cells must upregulate one or
      more of these transporters to satisfy their demand for amino acids. If the
      transporters that specifically serve this purpose in tumor cells are identified,
      they can be targeted for the development of a brand new class of anticancer
      drugs; the logical basis of such a strategy would be to starve the tumor cells of
      an important class of nutrients. To date, four amino acid transporters have been
      found to be expressed at high levels in cancer: SLC1A5, SLC7A5, SLC7A11, and
      SLC6A14. Their induction occurs in a cancer type-specific manner with a direct or
      indirect involvement of the oncogene c-Myc. Further, these transporters are
      functionally coupled, thus maximizing their ability to promote cancer growth and
      chemoresistance. Progress has been made in preclinical studies, exploiting these
      transporters as drug targets in cancer therapy. These transporters also show
      promise in development of new tumor-imaging probes and in tumor-specific delivery
      of appropriately designed chemotherapeutic agents.

PMID- 25855378
TI  - Vimentin-ERK Signaling Uncouples Slug Gene Regulatory Function.
AB  - Epithelial-mesenchymal transition (EMT) in cells is a developmental process
      adopted during tumorigenesis that promotes metastatic capacity. In this study, we
      advance understanding of EMT control in cancer cells with the description of a
      novel vimentin-ERK axis that regulates the transcriptional activity of Slug
      (SNAI2). Vimentin, ERK, and Slug exhibited overlapping subcellular localization
      in clinical specimens of triple-negative breast carcinoma. RNAi-mediated ablation
      of these gene products inhibited cancer cell migration and cell invasion through
      a laminin-rich matrix. Biochemical analyses demonstrated direct interaction of
      vimentin and ERK, which promoted ERK activation and enhanced vimentin
      transcription. Consistent with its role as an intermediate filament, vimentin
      acted as a scaffold to recruit Slug to ERK and promote Slug phosphorylation at
      serine-87. Site-directed mutagenesis established a requirement for ERK-mediated
      Slug phosphorylation in EMT initiation. Together, these findings identified a
      pivotal step in controlling the ability of Slug to organize hallmarks of EMT.

PMID- 25855380
TI  - Cell-Cell Adhesion and Cytoskeleton Tension Oppose Each Other in Regulating Tumor
      Cell Aggregation.
AB  - Cell aggregation is frequently impaired during the growth of primary tumors and
      the formation of metastatic lesions. Cell aggregation depends on cell-cell
      adhesion; however, no rigorous approach exists to monitor and quantify it
      accurately in the absence of the confounding factors of cell-substrate adhesion
      and the resulting cell motility on the substrate. We report here a highly
      reproducible, automated, microscopy-based quantification of tumor-cell spheroid
      formation in the absence of cell-substrate adhesion and use it to characterize
      cell aggregation dynamics in the early steps of this process. This method is
      based on fluorescence and bright-field microscopy and on a custom MATLAB program
      to quantify automatically the cells' aggregation kinetics. We demonstrate that
      the cell-cell adhesion protein E-cadherin and the desmosome proteins DSG2 and
      DSC2 are important for aggregation. Furthermore, we show that inhibition or
      silencing of myosin IIa enhances aggregation, suggesting that cytoskeleton
      tension inhibits tumor cell aggregation. This work opens new avenues to study the
      principles that govern multicellular aggregation, to characterize the aggregation
      properties of various tumor cell types, as well as to screen for drugs that
      inhibit or promote aggregation.

PMID- 25855381
TI  - Development of lung adenocarcinomas with exclusive dependence on oncogene
      fusions.
AB  - This report delivers a comprehensive genetic alteration profile of lung
      adenocarcinomas (LADC) driven by ALK, RET, and ROS1 oncogene fusions. These
      tumors are difficult to study because of their rarity. Each drives only a low
      percentage of LADCs. Whole-exome sequencing and copy-number variation analyses
      were performed on a Japanese LADC cohort (n = 200) enriched in patients with
      fusions (n = 31, 15.5%), followed by deep resequencing for validation. The driver
      fusion cases showed a distinct profile with smaller numbers of nonsynonymous
      mutations in cancer-related genes or truncating mutations in SWI/SNF chromatin
      remodeling complex genes than in other LADCs (P < 0.0001). This lower mutation
      rate was independent of age, gender, smoking status, pathologic stage, and tumor
      differentiation (P < 0.0001) and was validated in nine fusion-positive cases from
      a U.S. LADCs cohort (n = 230). In conclusion, our findings indicate that LADCs
      with ALK, RET, and ROS1 fusions develop exclusively via their dependence on these
      oncogene fusions. The presence of such few alterations beyond the fusions
      supports the use of monotherapy with tyrosine kinase inhibitors targeting the
      fusion products in fusion-positive LADCs.

PMID- 25855382
TI  - PLK1 and HOTAIR Accelerate Proteasomal Degradation of SUZ12 and ZNF198 during
      Hepatitis B Virus-Induced Liver Carcinogenesis.
AB  - Elucidating mechanisms of hepatitis B virus (HBV)-mediated hepatocarcinogenesis
      is needed to gain insights into the etiology and treatment of liver cancer. Cells
      where HBV is replicating exhibit increased expression of Plk1 kinase and reduced
      levels of two transcription repression factors, SUZ12 and ZNF198. SUZ12 is an
      essential subunit of the transcription repressive complex PRC2. ZNF198 stabilizes
      the transcription repressive complex composed of LSD1, Co-REST, and HDAC1. These
      two transcription repressive complexes are held together by binding the long
      noncoding RNA HOTAIR. In this study, we linked these regulatory events
      mechanistically by showing that Plk1 induces proteasomal degradation of SUZ12 and
      ZNF198 by site-specific phosphorylation. Plk1-dependent ubiquitination of SUZ12
      and ZNF198 was enhanced by expression of HOTAIR, significantly reducing SUZ12 and
      ZNF198 stability. In cells expressing the HBV X protein (HBx), downregulation of
      SUZ12 and ZNF198 mediated global changes in histone modifications. In turn, HBx
      expressing cells propagated an altered chromatin landscape after cell division,
      as exemplified by changes in histone modifications of the EpCAM promoter, a
      target of PRC2 and LSD1/Co-REST/HDAC1 complexes. Notably, liver tumors from X/c
      myc bitransgenic mice exhibited downregulation of SUZ12 and ZNF198 along with
      elevated expression of Plk1, HOTAIR, and EpCAM. Clinically, similar effects were
      documented in a set of HBV-related liver tumors consistent with the likelihood
      that downregulation of SUZ12 and ZNF198 leads to epigenetic reprogramming of
      infected hepatocytes. Because both Plk1 and HOTAIR are elevated in many human
      cancers, we propose that their combined effects are involved in epigenetic
      reprogramming associated broadly with oncogenic transformation.

PMID- 25855383
TI  - Tumor-induced pressure in the bone microenvironment causes osteocytes to promote
      the growth of prostate cancer bone metastases.
AB  - Cross-talk between tumor cells and their microenvironment is critical for
      malignant progression. Cross-talk mediators, including soluble factors and direct
      cell contact, have been identified, but roles for the interaction of physical
      forces between tumor cells and the bone microenvironment have not been described.
      Here, we report preclinical evidence that tumor-generated pressure acts to modify
      the bone microenvironment to promote the growth of prostate cancer bone
      metastases. Tumors growing in mouse tibiae increased intraosseous pressure.
      Application of pressure to osteocytes, the main mechanotransducing cells in bone,
      induced prostate cancer growth and invasion. Mechanistic investigations revealed
      that this process was mediated in part by upregulation of CCL5 and matrix
      metalloproteinases in osteocytes. Our results defined the critical contribution
      of physical forces to tumor cell growth in the tumor microenvironment, and they
      identified osteocytes as a critical mediator in the bone metastatic niche.

PMID- 25855384
TI  - Post-transplant liver function score as an early surrogate marker of long-term
      outcome.
AB  - BACKGROUND: Currently, there is no universally accepted method to evaluate liver
      function post-orthotopic liver transplant (OLTx) and there are no early surrogate
      function markers to assess the impact of perioperative interventions in trial
      settings. MATERIAL AND METHODS: In total, 495 patients were included in the
      study. On multivariate analysis, PTLF score, defined as normal (score <4) or
      dysfunctional (score >= 4), was the only significant variable for determining
      significant complications (P=0.014) and graft survival (P=002) during the
      perioperative period. RESULTS: In total, 495 patients were included in the study.
      On multivariate analysis, PTLF score, defined as normal (score <4) or
      dysfunctional (score >= 4), was the only significant variable for determining
      significant complications (P=0.014) and graft survival (P=002) during the
      perioperative period. CONCLUSIONS: PTLF score shows promise as an early surrogate
      marker of post-orthotopic liver transplantation mortality and morbidity by
      providing results within the first 7 days post-transplantation. PTLF score can
      potentially be used as a tool to assess the impact of perioperative interventions
      by predicting long-term outcomes early in the clinical course of transplant
      patients.

PMID- 25855385
TI  - Distribution and function of prophage phiRv1 and phiRv2 among Mycobacterium
      tuberculosis complex.
AB  - Mycobacterium tuberculosis complex (MTBC) is notorious for causing diseases, such
      as tuberculosis. Tuberculosis caused by M. tuberculosis remains a global public
      health concern. Two prophages, phiRv1 and phiRv2, can be found among most MTBC
      genomes. However, no precise functions have been assigned for the two prophages.
      In this paper, to find out the function of these two prophages, the distribution
      and function of phiRv1 and phiRv2 in MTBC genomes were analyzed from multiple
      omics data. We found that complex insertion, deletion, and reorganization
      appeared on the locus of two prophages in MTBC genomes; some genes of the two
      prophages can be translated and are functional from proteomic data; the
      expression of other prophage genes, such as Rv1577c, Rv2650c, Rv2652c, Rv2659c,
      and Rv2658c, can vary with environmental stresses and might enhance the fitness
      of MTBC. These data will facilitate our in-depth understanding of their function.

PMID- 25855386
TI  - How to encourage intrinsic motivation in the clinical teaching environment?: a
      systematic review from the self-determination theory.
AB  - PURPOSE: Internalization of students' motivation towards an intrinsic form is
      associated with increased interest, commitment, learning, and satisfaction with
      education. Self-Determination theory postulates that intrinsic motivation and
      autonomous forms of self-regulation are the desired type of motivation; as they
      have been associated with deep learning, better performance and well-being. It
      claims three basic psychological needs have to be satisfied in order to achieve
      intrinsic motivation. These are the needs for autonomy, competence and
      relatedness. This study aims to provide a review on how these basic psychological
      needs are encouraged in undergraduate students so they can be transferred to the
      clinical teaching environment. METHODS: Electronic searches were performed across
      four databases (Medline, Embase, PsycINFO, and ERIC), relevant journals, and
      retrieved bibliography of selected articles. In total, searches produced 4,869
      references, from which 16 studies met the inclusion criteria. RESULTS: Main
      themes were coded in three categories: The support of autonomy, competence and
      relatedness. The research-based evidence appears to be of reasonable quality, and
      indicates that teachers should work to satisfy students' basic psychological
      needs to foster internalization of self-regulation. Our findings suggest that
      teachers should interact with students in a more 'human centred' teaching style,
      as these actions predict motivational internalization. Several themes emerged
      from different contexts and further investigation should expand them. CONCLUSION:
      This review identified actions that clinical teachers could implement in their
      daily work to support students' self-determination. Autonomy supportive teaching
      in health professions educations would benefit students and may actually result
      in more effective health care delivery.

PMID- 25855387
TI  - Challenges in shifting to an integrated curriculum in a Caribbean medical school.

PMID- 25855388
TI  - Initiating small group learning in a Caribbean medical school.

PMID- 25855389
TI  - Dyslipidemia in Dialysis Patients.
AB  - Dyslipidemia is a well-established traditional risk factor for cardiovascular
      events in the general population, particularly those with preexisting
      cardiovascular disease (CVD). In this population, reductions in total and low
      density lipoprotein cholesterol (LDL-C) levels are effective in reducing coronary
      artery events and mortality. Dyslipidemia is more common in patients with chronic
      kidney disease (CKD) and is believed to contribute to the high prevalence of CVD
      in these patients. To date, the treatment of dyslipidemia in patients with CKD
      followed the guidelines recommended by the US National Cholesterol Education
      Program Adult Treatment Panel III (ATP III) for the treatment of lipid
      abnormalities. These guidelines recommend that initiation of lipid-lowering
      therapy be based on LDL-C level and the projected 10-year risk for coronary
      artery disease (CAD). However, we now recognize that the relationship between
      serum cholesterol and CVD is more complex in patients with CKD, particularly
      those receiving maintenance hemodialysis. This has been demonstrated by the
      failure of three large randomized clinical trials to show a beneficial effect of
      lipid-lowering therapy in reducing mortality in dialysis patients despite
      significant reduction in LDL-C levels. These results have caused uncertainty
      among nephrologists about how best to manage dyslipidemia in their patients. In
      this review, the role of dyslipidemia as a risk factor for atherosclerosis in
      ESRD patients and the results of the 3 clinical trials and other studies,
      including their limitations will be discussed, and a schema for treating
      dyslipidemia in dialysis patients will be proposed. 

PMID- 25855390
TI  - The down-regulation of disgust by implementation intentions: experiential and
      physiological concomitants.
AB  - Emotion regulation plays a key role in mental health and psychopathology.
      Therefore, it seems important to develop effective forms of emotion regulation.
      Implementation intentions are if-then plans that help people attain their self
      regulatory goals. Perspective-taking and response-focused implementation
      intentions have been shown to reduce feelings of unpleasantness and arousal,
      respectively, in response to briefly presented disgusting pictures. The present
      study addressed the open research questions whether forming these types of
      implementation intentions is effective in regulating affect during prolonged
      presentation of disgusting pictures, and whether it is associated with changes in
      physiological arousal. Eighty-one participants viewed disgusting, neutral, and
      pleasant pictures of 6 s duration under four instructions: the goal intention to
      not get disgusted, this goal intention furnished with a perspective-taking or a
      response-focused implementation intention, and no emotion regulation
      instructions. The dependent variables were ratings of disgust, valence, arousal,
      and electrodermal activity. Only perspective-taking implementation intention
      participants significantly reduced their disgust and unpleasantness as compared
      to goal-intention and control participants. Arousal and skin conductance did not
      significantly differ between conditions. The effectiveness of response-focused
      but not perspective-taking implementation intentions seems to be substantially
      reduced during sustained exposure duration.

PMID- 25855391
TI  - [Fatigue symptoms and workplace related factors of long-term care workers
      employed in facilities].
AB  - OBJECTIVES: "Regular visiting/on-demand response type long-term care" has
      recently been established. This will lead to a decrease in the burden on the
      family, but an increase in the burden of the care personnel who provide this kind
      of long-term care. The objectives of this study were to clarify the fatigue
      symptoms of long-term care workers in facilities that provide this kind of long
      term care, and examine the related factors in the workplace. METHODS: An
      anonymous questionnaire survey was conducted with 96 workers engaged in long-term
      care in facilities. The questionnaire was composed of cumulative fatigue symptoms
      index, work situation, supports in the workplace, and the attributes. The
      subjects were divided into two groups: those who had night shift between PM 6 to
      AM 8 with or without day shift (night shift group), and those who had only day
      shift (day shift group). The relationships between the fatigue symptom levels and
      work situation etc. were compared between the two groups. RESULTS: The night
      shift group consisted of 47 workers, whose mean age was 42.3 years and whose mean
      working experience was 6.0 years. The median number of persons they had visited
      in the previous month was 9. The day shift group consisted of 49 workers, whose
      mean age was 44.6 years and whose mean working experience was 5.9 years. The
      median number of persons they visited in the previous month was 9.5. Age and sex
      distributions showed no difference between the two groups. There was no
      difference in the work situations and the supports in the workplace, except for
      working time and the details of care the subjects were providing. The fatigue
      symptom levels were high in both groups, but in the night shift group the level
      of physical disorders was higher than in the day shift group. Satisfaction with
      work, education and training for mental health and consideration for traffic
      safety when making home visits were negatively related to fatigue symptom levels
      in both groups. Learning care during the previous year, and the ease of receiving
      paid holiday were not related to the fatigue symptom levels in the night shift
      group. This was different in the day shift group. CONCLUSIONS: Measures of
      fatigue symptoms should be performed for both groups. It is desirable that
      supports, additional to that given in the workplace to the day shift group, be
      given to the night shift group, and its efficacy be researched.

PMID- 25855393
TI  - Cardiac magnetic resonance imaging reveals extensive biventricular fibrosis and
      inflammation challenging the diagnosis of ARVC.

PMID- 25855392
TI  - Extracellular remodeling in patients with wild-type amyloidosis consuming
      epigallocatechin-3-gallate: preliminary results of T1 mapping by cardiac magnetic
      resonance imaging in a small single center study.
AB  - OBJECTIVES: T1 mapping by cardiac magnetic resonance imaging (CMR) is able to
      determine the extracellular volume fraction. Wild-type transthyretin amyloidosis
      (WT-ATTR) is characterized by extracellular amyloid deposition in the heart.
      Recent reports indicated a reduction of left ventricular (LV) myocardial mass in
      WT-ATTR after consumption of epigallocatechin-3-gallate, the main catechin in
      green tea. It remained unclear, whether reduction of LV myocardial mass reflects
      decrease of amyloid load or progressive atrophy of cardiomyocytes. METHODS: This
      study included 7 male patients with CMR repetitively performed before and 12
      months after daily consumption of green tea extract (600 mg epigallocatechin-3
      gallate). Short axis slices as well as 2-, 3-, and 4-chamber views were acquired
      using SSFP sequences. T1 mapping was created out of 11 mid-ventricular short axis
      views with increasing inversion times using a single breath-hold modified look
      locker inversion recovery sequence before and 15 min after Gadolinium contrast
      administration. RESULTS: After 12 months, a significant decrease of LV myocardial
      mass [198 (160; 212) vs. 180 (142; 204) g; p < 0.05] was observed. Moreover, a
      significant decrease of native [T1 1110 (1072; 1150) ms vs. 1080 (970; 1101), p <
      0.05 or p = 0.03] was noticed. The calculated extracellular volume decreased in 5
      patients (62.5%) by 7% and increased in 2 patients (37.5%) by 9.5%, in trend
      resulting in a (not significant) decrease of median ECV by 2.4%. Left ventricular
      ejection fraction (LVEF) [57 (48; 65) vs. 55 (47; 64) %; p = 0.3] remained
      unchanged. CONCLUSIONS: This study provided further evidence of LV myocardial
      mass reduction in patients with WT-ATTR daily consuming green tea extract.
      Additionally, this study gave first insights into the histomorphological
      correlate of LV mass reduction using T1 mapping. LV mass reduction appeared to be
      rather due to a decrease of amyloid load than atrophy of cardiomyocytes.

PMID- 25855394
TI  - Abnormal mitral-aortic intervalvular coupling in mitral valve diseases: a study
      using real-time three-dimensional transesophageal echocardiography.
AB  - BACKGROUND: Mitral and aortic valves are coupled via fibrous tissue. This
      coupling is considered to be important for cardiac function before and after
      mitral valve surgery. The relationship between mitral-aortic coupling and
      different types of mitral regurgitation (MR) is not completely understood.
      METHODS AND RESULTS: Real-time three-dimensional transesophageal echocardiography
      (RT3D-TEE) was performed in 133 subjects: 30 normal subjects, 15 patients with
      Carpentier type I MR (annular dilatation and congenital cleft), 40 type II
      (mitral valve prolapse), 20 type IIIa (rheumatic) and 28 type IIIb (ischemic
      mitral regurgitation). Custom software was used to track mitral (MA) and aortic
      annuli (AoA) in 3D space throughout cardiac cycle, allowing measurement of
      changes in mitral and aortic valve morphology. Normal mitral-aortic coupling is
      characterized by reciprocal changes in the annular areas throughout cardiac
      cycle, with systolic reduction of the angle between the two annular planes. In
      Carpentier type II patients, not only MA but also AoA areas were increased (P <
      0.05 vs normal), but the reciprocal pattern of mitral-aortic coupling was
      preserved. In both type I IMR and IIIb patients, MA and AoA areas were both
      increased (P < 0.05 vs normal) and the reciprocal behavior of mitral-aortic
      coupling was lost. Only MA area was increased in type IIIa patients. The extent
      of mitral-aortic angle reduction during systole was diminished in all 4
      Carpentier groups (P < 0.05 vs normal). CONCLUSIONS: Mitral valve diseases may
      affect normal mitral-aortic coupling and aortic valve function. Different
      patterns of abnormal mitral-aortic coupling are associated with different
      Carpentier types of MR.

PMID- 25855395
TI  - How do nurses experience working with adolescents with a diagnosis of
      'personality disorder' or 'emerging personality disorder'?
AB  - Nurses experience adults with a diagnosis of 'personality disorder' ('PD') as
      challenging, but nothing is known of their experiences working with young people
      with a diagnosis of 'PD' or 'emerging PD'. This study aimed to explore the
      experiences of nurses with this group. Six nurses were interviewed individually
      and the transcripts analysed employing interpretative phenomenological analysis.
      Two themes were identified: emotional impact, and conflict and need for support.
      Participants described powerful emotional responses and heavy time demands as
      particular challenges. They also reflected on tensions that arose in the wider
      team and service context. The importance of reflective space, training and the
      need for specialist approaches, such as therapeutic input, was emphasized by all
      participants. The study's findings suggest that while there are some similarities
      to adult services, there are also issues specific to nursing adolescents with
      'PD', which merit further attention, including the implications of the lack of
      diagnostic clarity for treatment approaches and the difficult interpersonal
      dynamics of the condition. Recommendations for practice include additional
      training in relation to the theoretical understanding of diagnosis itself and in
      working therapeutically with young people with the diagnosis, employing
      approaches that have been found to be useful in adult services.

PMID- 25855396
TI  - Higher ratio of ischemic stroke to hemorrhagic stroke in summer.
AB  - BACKGROUND: The aim of this study was to investigate the seasonal variation of
      the ratio of hemorrhagic stroke to ischemic stroke. The working hypothesis is
      that the ratio may vary among seasons. METHODS: A total of 13,788 patients
      registered in the Kyoto Stroke Registry from 1999 to 2009 were divided into 4
      groups based on the season in which stroke developed. We calculated odds ratio
      (OR) for the incidence of stroke as a whole, cerebral infarction (CeI), cerebral
      hemorrhage (CH), and subarachnoid hemorrhage (SAH) in spring, autumn, and winter
      setting summer as a reference. Using a logistic regression, we evaluated the
      seasonal variation of ORs for CH/CeI and for SAH/CeI with adjustment for age,
      gender, and risk factors. RESULTS: Incidence of CeI in autumn was lower than in
      summer (OR: 0.93; 0.87-0.98, P = 0.013). Incidence of CH was higher in spring
      (OR: 1.36; 1.23-1.49, P < 0.001), in autumn (OR: 1.16; 1.05-1.28, P = 0.004), and
      in winter (OR: 1.37; 1.25-1.51, P < 0.001) than in summer. Incidence of SAH was
      higher in spring (OR: 1.51; 1.28-1.79, P < 0.001) and in winter (OR: 1.44; 1.22
      1.70, P < 0.001) than in summer. OR for CH/CeI in spring, autumn, and winter were
      1.28 (1.13-1.45, P < 0.001), 1.26 (1.11-1.43, P < 0.001), and 1.35 (1.19-1.53, P
      < 0.001), respectively. ORs for SAH/CeI were 1.46 (1.19-1.79, P < 0.001), 1.34
      (1.09-1.66, P = 0.007), and 1.50 (1.22-1.84, P < 0.001), respectively.
      CONCLUSIONS: Seasonal variations differed among stroke subtypes. The OR for
      CH/CeI and for SAH/CeI was lower in summer and higher in the rest of seasons
      independent of age, gender, and risk factors.

PMID- 25855397
TI  - Clinical studies of the treatment of facial atrophic acne scars and acne with a
      bipolar fractional radiofrequency system.
AB  - Few clinical studies have examined the utility of bipolar fractional
      radiofrequency (FRF) therapy as a treatment for atrophic acne scars and active
      acne in people with darker skin. This study was designed to compare the safety
      and efficacy of bipolar FRF therapy as a treatment for atrophic acne scars and
      acne vulgaris. Twenty-three Japanese patients with atrophic acne scars and mild
      to severe acne on both cheeks were treated with a bipolar FRF system (eMatrix;
      Syneron, Yokneam Illit, Israel). Five treatment sessions were carried out at 1
      month intervals, and the patients were followed up for 3 months after the final
      treatment. Assessments of scar severity and the number of acne lesions and 3-D in
      vivo imaging analysis were performed. Evaluations of the treatment outcomes and
      their effects on the patients' quality of life (QOL) were also carried out. We
      demonstrated that the improvement in scar volume was marked in the patients with
      mild scars and was at least moderate in 23 (57.5%) of the treated areas. With
      regard to the number of acne lesions, the treated areas exhibited significantly
      fewer lesions compared with the baseline at each time point (P < 0.05). The
      patients' assessments of the treatment outcomes and their QOL indicated that both
      had improved significantly by the end of the study. Furthermore, significant
      reductions in the patients' sebum levels, skin roughness and scar depth were
      observed. Bipolar FRF treatment significantly improved the atrophic acne scars
      and acne of Japanese patients and had minimal side-effects. 

PMID- 25855398
TI  - Lethal arrhythmia due to fingolimod, a S1P receptor modulator: are we
      overestimating or underestimating?

PMID- 25855399
TI  - A second chance--reoperation in patients with failed surgery for intractable
      epilepsy: long-term outcome, neuropsychology and complications.
AB  - OBJECT: Resective surgery is a safe and effective treatment of drug-resistant
      epilepsy. If surgery has failed reoperation after careful re-evaluation may be a
      reasonable option. This study was to summarise the risks and benefits of
      reoperation in patients with epilepsy. METHODS: This is a retrospective single
      centre study comprising clinical data, long-term seizure outcome,
      neuropsychological outcome and postoperative complications of patients, who had
      undergone a second resective epilepsy surgery from 1989 to 2009. RESULTS: A total
      of 66 patients with median follow-up of 10.3 years were included into the study.
      Fifty-one patients (77%) had surgery for temporal lobe epilepsy, the remaining 15
      cases for extra-temporal lobe epilepsies. The most frequent histological findings
      were tumours (n=33, 50%), followed by dysplasia, gliosis (n=11, each) and
      hippocampus sclerosis (n=9). The main reasons for seizure recurrence were
      incomplete resection (59.1%) of the putative epileptogenic lesion. After
      reoperation 46 patients (69.7%) were completely seizure-free International League
      Against Epilepsy 1 (ILAE 1) at the last available follow-up. The
      neuropsychological evaluation demonstrated that repeated losses in the same
      cognitive domain, that is, successive changes from better to worse performance
      categories, were rare and that those losses after first surgery were followed by
      improvement rather than decline. However, reoperations lead to an increased rate
      of permanent neurological deficits (9%), overall surgical complications (9%) and
      visual field deficits (67%). CONCLUSIONS: Reoperation after failed resective
      epilepsy surgery led to approximately 70% long-time seizure freedom and
      reasonable neuropsychological outcome. There is an increased risk of permanent
      postoperative neurological deficits, which should be taken into consideration
      when counselling for reoperation.

PMID- 25855400
TI  - Hospital revisit rate after a diagnosis of conversion disorder.
AB  - OBJECTIVE: To estimate the hospital revisit rate of patients diagnosed with
      conversion disorder (CD). METHODS: Using administrative data, we identified all
      patients discharged from California, Florida and New York emergency departments
      (EDs) and acute care hospitals between 2005 and 2011 with a primary discharge
      diagnosis of CD. Patients discharged with a primary diagnosis of seizure or
      transient global amnesia (TGA) served as control groups. Our primary outcome was
      the rate of repeat ED visits and hospital admissions after initial presentation.
      Poisson regression was used to compare rates between diagnosis groups while
      adjusting for demographic characteristics. RESULTS: We identified 7946 patients
      discharged with a primary diagnosis of CD. During a mean follow-up of 3.0 (+/
      1.6) years, patients with CD had a median of three (IQR, 1-9) ED or inpatient
      revisits, compared with 0 (IQR, 0-2) in patients with TGA and 3 (IQR, 1-7) in
      those with seizures. Revisit rates were 18.25 (95% CI, 18.10 to 18.40) visits per
      100 patients per month in those with CD, 3.90 (95% CI, 3.84 to 3.95) in those
      with TGA and 17.78 (95% CI, 17.75 to 17.81) in those with seizures. As compared
      to CD, the incidence rate ratio for repeat ED visits or hospitalisations was 0.89
      (95% CI, 0.86 to 0.93) for seizure disorder and 0.32 (95% CI 0.31 to 0.34) for
      TGA. CONCLUSIONS: CD is associated with a substantial hospital revisit rate. Our
      findings suggest that CD is not an acute, time-limited response to stress, but
      rather that CD is a manifestation of a broader pattern of chronic
      neuropsychiatric disease.

PMID- 25855401
TI  - Weakened functional connectivity in patients with psychogenic non-epileptic
      seizures (PNES) converges on basal ganglia.
AB  - BACKGROUND: Psychogenic non-epileptic seizures (PNES) are involuntary paroxysmal
      events that are unaccompanied by epileptiform EEG discharges. We hypothesised
      that PNES are a disorder of distributed brain networks resulting from their
      functional disconnection.The disconnection may underlie a dissociation mechanism
      that weakens the influence of unconsciously presented traumatising information
      but exerts maladaptive effects leading to episodic failures of behavioural
      control manifested by psychogenic 'seizures'. METHODS: To test this hypothesis,
      we compared functional connectivity (FC) derived from resting state high-density
      EEGs of 18 patients with PNES and 18 age-matched and gender-matched controls. To
      this end, the EEGs were transformed into source space using the local
      autoregressive average inverse solution. FC was estimated with a multivariate
      measure of lagged synchronisation in the theta, alpha and beta frequency bands
      for 66 brain sites clustered into 18 regions. A multiple comparison permutation
      test was applied to deduce significant between-group differences in inter
      regional and intraregional FC. RESULTS: The significant effect of PNES-a decrease
      in lagged FC between the basal ganglia and limbic, prefrontal, temporal, parietal
      and occipital regions-was found in the alpha band. CONCLUSION: We believe that
      this finding reveals a possible neurobiological substrate of PNES, which explains
      both attenuation of the effect of potentially disturbing mental representations
      and the occurrence of PNES episodes. By improving understanding of the aetiology
      of this condition, our results suggest a potential refinement of diagnostic
      criteria and management principles.

PMID- 25855402
TI  - Real world data on acute myeloid leukaemia therapy from the developing world--an
      eye-opener.

PMID- 25855403
TI  - Pancreatic cancer: A matter of timing.

PMID- 25855405
TI  - Evaluating tissue oxygenation at the bedside: global, regional, or both?
AB  - Early recognition of tissue hypoperfusion, and monitoring tissue response to
      resuscitation interventions, are key points in the management of critically ill
      patients. In the present issue of J Clin Monit Comput, Dr. Koch and coworkers
      present the results of a study evaluating regional and global markers of tissue
      perfusion in a population of septic shock patients. We propose an integrative
      approach to tissue perfusion assessment, where combining both, global and
      regional variables, might account for a better understanding of tissue
      oxygenation status, and might prove useful for septic shock patients' management.

PMID- 25855404
TI  - Heterogeneity of epidermal growth factor receptor signalling networks in
      glioblastoma.
AB  - As tumours evolve, the daughter cells of the initiating cell often become
      molecularly heterogeneous and develop different functional properties and
      therapeutic vulnerabilities. In glioblastoma (GBM), a lethal form of brain
      cancer, the heterogeneous expression of the epidermal growth factor receptor
      (EGFR) poses a substantial challenge for the effective use of EGFR-targeted
      therapies. Understanding the mechanisms that cause EGFR heterogeneity in GBM
      should provide better insights into how they, and possibly other amplified
      receptor tyrosine kinases, affect cellular signalling, metabolism and drug
      resistance. 

PMID- 25855406
TI  - Sulfur-Responsive Elements in the 3'-Nontranscribed Intergenic Region Are
      Essential for the Induction of SULFATE TRANSPORTER 2;1 Gene Expression in
      Arabidopsis Roots under Sulfur Deficiency.
AB  - Under sulfur deficiency (-S), plants induce expression of the sulfate transport
      systems in roots to increase uptake and root-to-shoot transport of sulfate. The
      low-affinity sulfate transporter SULTR2;1 is predominantly expressed in xylem
      parenchyma and pericycle cells in Arabidopsis thaliana roots under -S. The
      mechanisms underlying -S-inducible expression of SULTR2;1 in roots have remained
      unclear, despite the possible significance of SULTR2;1 for acclimation to low
      sulfur conditions. In this investigation, examination of deletions and base
      substitutions in the 3'-intergenic region of SULTR2;1 revealed novel sulfur
      responsive elements, SURE21A (5'-CAATGTATC-3') and SURE21B (5'-CTAGTAC-3'),
      located downstream of the SULTR2;1 3'-untranslated region. SURE21A and SULTR21B
      effectively induced reporter gene expression from fusion constructs under -S in
      combination with minimal promoters or promoters not inducible by -S, suggesting
      their versatility in controlling transcription. T-DNA insertions near SURE21A and
      SULTR21B abolished -S-inducible expression of SULTR2;1 in roots and reduced the
      uptake and root-to-shoot transport of sulfate. In addition, these mutations
      partially suppressed SULTR2;1 expression in shoots, without changing its -S
      responsive expression. These findings indicate that SULTR2;1 contributes to the
      increase in uptake and internal translocation of sulfate driven by gene
      expression induced under the control of sulfur-responsive elements in the 3'
      nontranscribed intergenic region of SULTR2;1. 

PMID- 25855407
TI  - Exometabolomics and MSI: deconstructing how cells interact to transform their
      small molecule environment.
AB  - Metabolism is at the heart of many biotechnologies from biofuels to medical
      diagnostics. Metabolomic methods that provide glimpses into cellular metabolism
      have rapidly developed into a critical component of the biotechnological
      development process. Most metabolomics methods have focused on what is happening
      inside the cell. Equally important are the biochemical transformations of the
      cell, and their effect on other cells and their environment; the exometabolome.
      Exometabolomics is therefore gaining popularity as a robust approach for
      obtaining rich phenotypic data, and being used in bioprocessing and biofuel
      development. Mass spectrometry imaging approaches, including several
      nanotechnologies, provide complimentary information by localizing metabolic
      processes within complex biological matrices. Together, the two technologies can
      provide new insights into the metabolism and interactions of cells. 

PMID- 25855408
TI  - Gene expression of key regulators of mitochondrial biogenesis is sex dependent in
      mice with growth hormone receptor deletion in liver.
AB  - Mitochondrial biogenesis is an essential process for cell viability. Mice with
      disruption of the growth hormone receptor (GHR) gene (Ghr gene) in the liver
      (LiGHRKO), in contrast to long-lived mice with global deletion of the Ghr gene
      (GHRKO), are characterized by lack of improved insulin sensitivity and severe
      hepatic steatosis. Tissue-specific disruption of the GHR in liver results in a
      mouse model with dramatically altered GH/IGF1 axis. We have previously shown
      increased levels of key regulators of mitochondrial biogenesis in insulin
      sensitive GHRKO mice. The aim of the present study is to assess, using real-time
      PCR, the gene expression of key regulators of mitochondrial biogenesis
      (Pgc1alpha, Ampk, Sirt1, Nrf2 and Mfn2) and a marker of mitochondrial activity
      (CoxIV) in brains, kidneys and livers of male and female LiGHRKO and wild-type
      (WT) mice. There were significant differences between males and females. In the
      brain, expression of Pgc1alpha, Ampk, Sirt1, Nrf2 and Mfn2 was lower in pooled
      females compared to pooled males. In the kidneys, expression of Ampk and Sirt1
      was also lower in female mice. In the liver, no differences between males and
      females were observed. Sexual dimorphism may play an important role in regulating
      the biogenesis of mitochondria. 

PMID- 25855409
TI  - Partial semitendinosus tendon tear in a young athlete: a case report and review
      of the distal semitendinosus anatomy.
AB  - Distal semitendinosus tears have been infrequently reported in the radiology
      literature, and a detailed description of the anatomy and imaging features of
      these injuries is lacking. The semitendinosus tendon is clinically relevant, as
      it is frequently grafted in knee ligament reconstructions and plays an important
      role in performing competitive activities. We present a case of a 31-year-old man
      who developed a partial semitendinosus tear during competitive training. This
      case highlights the common clinical and imaging findings found with distal
      semitendinosus tears, and explores the various modalities available to treat this
      injury. We also review the clinically pertinent anatomy of the distal
      semitendinosus tendon and discuss the pitfalls that musculoskeletal radiologists
      may encounter, to avoid misdiagnosing these rare injuries.

PMID- 25855410
TI  - Atypical, unusual, and misleading imaging presentations of spondylolysis.
AB  - Although lumbar spondylolysis is a widely known and easily recognizable condition
      in its typical presentation, there are some less well-known forms that may
      occasionally be challenging and/or demand special attention on imaging. Examples
      include: acute and/or incomplete lesions; unilateral defects; lesions at unusual
      levels (cervical, upper lumbar, and multi-level spondylolyses); iatrogenic
      lesions; non-isthmic spondylolysis; and spondylolysis related to underlying
      diseases. In addition to their atypical, uncommon or confusing imaging
      presentations, these forms of spondylolysis are far rarer than the classic type
      and have been described, to a great extent, in the surgical literature, thus
      reducing the awareness of radiologists about them and raising the potential for
      misdiagnosis and inadequate treatment. In this review the authors address these
      special manifestations of spondylolysis, stressing the more important features to
      be considered in the differential diagnosis and the impact of a precise diagnosis
      of spondylolysis on the patient's care. 

PMID- 25855411
TI  - High intrinsic carrier mobility and photon absorption in the perovskite
      CH3NH3PbI3.
AB  - The carrier transport and optical properties of the hybrid organic-inorganic
      perovskite CH3NH3PbI3 are investigated using first-principles approaches. We
      found that the electron and hole mobilities could reach surprisingly high values
      of 7-30 * 10(3) and 1.5-5.5 * 10(3) cm(2) V(-1) s(-1), respectively, and both are
      estimated to be much higher than the current experimental measurements. The high
      carrier mobility is ascribed to the intrinsically small effective masses of anti
      bonding band-edge states. The above results imply that there is still space to
      improve the performance of related solar cells. This material also has a sharp
      photon absorption edge and an absorption coefficient as high as 10(5) cm(-1),
      both of which contribute to effective utilization of solar radiation. Although
      band-edge states are mainly derived from the inorganic ions of Pb and I, thermal
      movement of the organic base has indirect influences on the bandgap and carrier
      effective masses, resulting in the temperature-dependent solar cell efficiencies.

PMID- 25855412
TI  - Subacute cutaneous lupus erythematosus induced by lansoprazole.

PMID- 25855413
TI  - Outcome and toxicities associated to chemotherapy in children with acute
      lymphoblastic leukemia and Gilbert syndrome. Usefulness of UGT1A1 mutational
      screening.
AB  - BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most frequent cancer in
      childhood. Although intensive chemotherapy has improved survival in those
      patients, important side effects, including hyperbilirubinemia, are frequent.
      Gilbert syndrome (GS) is a frequent condition that causes a reduction in
      glucuronidation and intermittent hyperbilirubinemia episodes. This could provoke
      a greater exposure to some cytotoxic agents used in ALL, increasing the risk of
      toxicity. On the other hand, unexplained hyperbilirubinemia could lead to
      unnecessary modifications or even treatment withdrawals, which could increase the
      risk of relapse, but data regarding this in ALL pediatric population are scarce.
      METHODS: Retrospective study to analyze toxicity, outcome and treatment
      modifications related to GS in children diagnosed with ALL. RESULTS: A total of
      23 of 159 patients were diagnosed with GS. They had statistically higher
      hyperbilirubinemias during all treatment phases (P < 0.0001) and a slower
      methotrexate clearance when it was administered during a 24-hr infusion at high
      doses (patients with GS: 74 hr +/- 19 vs. patients without GS: 64 hr +/- 8; P < 
      .002). However, no relevant toxicity or delays in treatment were found in them.
      Finally, changes in treatment due to hyperbilirubinemia were only done in 5
      patients with GS. CONCLUSIONS: Differences in outcome were not found in patients
      with GS. Universal screening for GS appears to be not necessary in pediatric
      patients with ALL. However, when hyperbilirubinemia is observed, it must be rule
      out in order to avoid unnecessary changes in treatment.

PMID- 25855414
TI  - Facile synthesis of nucleic acid-polymer amphiphiles and their self-assembly.
AB  - A solid-phase synthesis for nucleic acid-polymer amphiphiles is developed. Using
      this strategy, several DNA-b-polymer amphiphiles are synthesized, and their self
      assembly in aqueous solution is investigated. This general method can in
      principle be extended to nearly all polymers synthesized by atom transfer radical
      polymerization to produce a variety of nucleic acid-polymer conjugates. 

PMID- 25855415
TI  - Prosthetics for nasal perforations: a systematic review and meta-analysis.
AB  - OBJECTIVE: Prosthetics serve as an option for nasoseptal perforation treatment in
      patients who have active systemic disease, are poor surgical candidates, or wish
      to avoid surgery. Through systematic review of the literature on prosthetics for
      nasoseptal perforation treatment, the objective of the present study is to
      critically appraise previous studies, evaluate the success rate for nasoseptal
      prosthetics, provide evidence-based guidelines for nasoseptal prosthetic use, and
      identify areas for further investigation. DATA SOURCES: Cochrane Controlled
      Trials Register, EMBASE, PubMed, and Web of Science. REVIEW METHODS: Data sources
      were queried for relevant articles published from 1965 to 2013. Articles were
      selected for inclusion if they presented primary data for human nasoseptal
      perforation treatment utilizing prosthetic materials. Each included article's
      level of evidence and risk of bias were identified and grades of recommendation
      were assigned. A quantitative meta-analysis was performed on articles with low
      risk of bias. RESULTS: The search yielded 4756 abstracts for review, with 23
      included case series and 5 case reports; 706 total cases of prosthetic nasoseptal
      perforation treatment were identified. All articles provided level 4 evidence,
      with an overall conclusion grade of C for improvement in nasoseptal perforation
      symptoms, prosthetic in situ rate, and complication rate. Meta-analysis of 6 low
      risk-of-bias studies with 297 patients demonstrated an overall success rate of
      65%. CONCLUSIONS: The literature provides level 4 evidence for the efficacy and
      safety of prosthetics for nasoseptal perforation treatment with favorable success
      rates and few reports of complications--only 1 fungal infection and 9 unspecified
      infections-in 706 cases.

PMID- 25855416
TI  - The role of parotidectomy in the treatment of auricular squamous cell carcinoma.
AB  - OBJECTIVE: We analyze parotid specimens in patients treated with prophylactic
      parotidectomy for squamous cell carcinoma of the auricle greater than or equal to
      2 cm to determine rates of metastasis and the efficacy of elective resection.
      STUDY DESIGN: Case series with chart review. SETTING: Cancer treatment center in
      Fort Worth, Texas, from 1998 to 2013. SUBJECTS AND METHODS: The study included
      104 patients between ages 36 and 97 years with primary auricular squamous cell
      carcinoma greater than or equal to 2 cm, with no evidence of adenopathy or
      parotid involvement on imaging. Patients underwent local excision and ipsilateral
      parotidectomy. The primary cancer was analyzed for vascular involvement,
      perineural invasion, and cartilage involvement, while the parotid specimen was
      analyzed for cancer positivity. RESULTS: Thirty-nine parotid (37.5%) samples were
      positive for carcinoma. Of these, 16 patients had primary auricular carcinomas
      with vascular involvement, 17 had perineural invasion, and 4 had cartilage
      involvement. Thirty-two of 77 affected men and 7 of 27 affected women had
      positive parotid specimen. Vascular involvement (P = .0006) and perineural
      invasion (P = .0027) of the primary lesion were significantly higher in patients
      with a positive parotid specimen. Cartilage involvement and sex were not
      statistically significant. CONCLUSIONS: Elective parotidectomy is beneficial in
      patients with squamous cell carcinoma of the auricle at least 2 cm in size,
      especially in lesions having perineural invasion and vascular involvement. For
      patients with positive parotid specimens, we recommend postoperative external
      beam radiation therapy and close surveillance.

PMID- 25855417
TI  - A Horrible Experiment.
AB  - A patient presented to my office who had been tortured in the course of a wartime
      medical experiment many years ago. Seeing him prompted me to explore my personal
      reaction to his case and to reflect on the history of the ethics of medical
      experimentation in the 20th century. 

PMID- 25855418
TI  - All that glitters.

PMID- 25855419
TI  - Seeds of change.

PMID- 25855420
TI  - Lunar affairs.

PMID- 25855421
TI  - Test the effects of ash on jet engines.

PMID- 25855433
TI  - Race to stamp out animal plague begins.

PMID- 25855435
TI  - Synthetic biology called to order.

PMID- 25855434
TI  - Physicists, your planet needs you.

PMID- 25855436
TI  - Africa aims for research autonomy.

PMID- 25855437
TI  - The future of the postdoc.

PMID- 25855438
TI  - Materials science: The hole story.

PMID- 25855439
TI  - Core services: Reward bioinformaticians.

PMID- 25855443
TI  - Whaling review: No case for Japan to kill minke whales.

PMID- 25855444
TI  - International sanctions: Sanctions in Iran disrupt cancer care.

PMID- 25855446
TI  - Space missions: Another two-body trick before Dawn.

PMID- 25855445
TI  - Ecosystem services: Academies review insecticide harm.

PMID- 25855447
TI  - Data management: One scientist's data as another's noise.

PMID- 25855448
TI  - Zofia Kielan-Jaworowska (1925-2015).

PMID- 25855449
TI  - Planetary science: Prebiotic chemistry on the rocks.

PMID- 25855450
TI  - Nuclear chemistry: Lawrencium bridges a knowledge gap.

PMID- 25855451
TI  - Neuroscience: Binge drinking and brain stress systems.

PMID- 25855453
TI  - Solar System: An incredible likeness of being.

PMID- 25855455
TI  - The comet-like composition of a protoplanetary disk as revealed by complex
      cyanides.
AB  - Observations of comets and asteroids show that the solar nebula that spawned our
      planetary system was rich in water and organic molecules. Bombardment brought
      these organics to the young Earth's surface. Unlike asteroids, comets preserve a
      nearly pristine record of the solar nebula composition. The presence of cyanides
      in comets, including 0.01 per cent of methyl cyanide (CH3CN) with respect to
      water, is of special interest because of the importance of C-N bonds for abiotic
      amino acid synthesis. Comet-like compositions of simple and complex volatiles are
      found in protostars, and can readily be explained by a combination of gas-phase
      chemistry (to form, for example, HCN) and an active ice-phase chemistry on grain
      surfaces that advances complexity. Simple volatiles, including water and HCN,
      have been detected previously in solar nebula analogues, indicating that they
      survive disk formation or are re-formed in situ. It has hitherto been unclear
      whether the same holds for more complex organic molecules outside the solar
      nebula, given that recent observations show a marked change in the chemistry at
      the boundary between nascent envelopes and young disks due to accretion shocks.
      Here we report the detection of the complex cyanides CH3CN and HC3N (and HCN) in
      the protoplanetary disk around the young star MWC 480. We find that the abundance
      ratios of these nitrogen-bearing organics in the gas phase are similar to those
      in comets, which suggests an even higher relative abundance of complex cyanides
      in the disk ice. This implies that complex organics accompany simpler volatiles
      in protoplanetary disks, and that the rich organic chemistry of our solar nebula
      was not unique. 

PMID- 25855454
TI  - Climate change and the permafrost carbon feedback.
AB  - Large quantities of organic carbon are stored in frozen soils (permafrost) within
      Arctic and sub-Arctic regions. A warming climate can induce environmental changes
      that accelerate the microbial breakdown of organic carbon and the release of the
      greenhouse gases carbon dioxide and methane. This feedback can accelerate climate
      change, but the magnitude and timing of greenhouse gas emission from these
      regions and their impact on climate change remain uncertain. Here we find that
      current evidence suggests a gradual and prolonged release of greenhouse gas
      emissions in a warming climate and present a research strategy with which to
      target poorly understood aspects of permafrost carbon dynamics. 

PMID- 25855456
TI  - Four-wave mixing experiments with extreme ultraviolet transient gratings.
AB  - Four-wave mixing (FWM) processes, based on third-order nonlinear light-matter
      interactions, can combine ultrafast time resolution with energy and wavevector
      selectivity, and enable the exploration of dynamics inaccessible by linear
      methods. The coherent and multi-wave nature of the FWM approach has been crucial
      in the development of advanced technologies, such as silicon photonics,
      subwavelength imaging and quantum communications. All these technologies operate
      at optical wavelengths, which limits the spatial resolution and does not allow
      the probing of excitations with energy in the electronvolt range. Extension to
      shorter wavelengths--that is, the extreme ultraviolet and soft-X-ray ranges-
      would allow the spatial resolution to be improved and the excitation energy range
      to be expanded, as well as enabling elemental selectivity to be achieved by
      exploiting core resonances. So far, FWM applications at such wavelengths have
      been prevented by the absence of coherent sources of sufficient brightness and of
      suitable experimental set-ups. Here we show how transient gratings, generated by
      the interference of coherent extreme-ultraviolet pulses delivered by the FERMI
      free-electron laser, can be used to stimulate FWM processes at suboptical
      wavelengths. Furthermore, we have demonstrated the possibility of observing the
      time evolution of the FWM signal, which shows the dynamics of coherent
      excitations as molecular vibrations. This result opens the way to FWM with
      nanometre spatial resolution and elemental selectivity, which, for example, would
      enable the investigation of charge-transfer dynamics. The theoretical possibility
      of realizing these applications has already stimulated ongoing developments of
      free-electron lasers: our results show that FWM at suboptical wavelengths is
      feasible, and we hope that they will enable advances in present and future photon
      sources.

PMID- 25855457
TI  - Measurement of the first ionization potential of lawrencium, element 103.
AB  - The chemical properties of an element are primarily governed by the configuration
      of electrons in the valence shell. Relativistic effects influence the electronic
      structure of heavy elements in the sixth row of the periodic table, and these
      effects increase dramatically in the seventh row--including the actinides--even
      affecting ground-state configurations. Atomic s and p1/2 orbitals are stabilized
      by relativistic effects, whereas p3/2, d and f orbitals are destabilized, so that
      ground-state configurations of heavy elements may differ from those of lighter
      elements in the same group. The first ionization potential (IP1) is a measure of
      the energy required to remove one valence electron from a neutral atom, and is an
      atomic property that reflects the outermost electronic configuration. Precise and
      accurate experimental determination of IP1 gives information on the binding
      energy of valence electrons, and also, therefore, on the degree of relativistic
      stabilization. However, such measurements are hampered by the difficulty in
      obtaining the heaviest elements on scales of more than one atom at a time. Here
      we report that the experimentally obtained IP1 of the heaviest actinide,
      lawrencium (Lr, atomic number 103), is 4.96(+0.08)(-0.07) electronvolts. The IP1
      of Lr was measured with (256)Lr (half-life 27 seconds) using an efficient surface
      ion-source and a radioisotope detection system coupled to a mass separator. The
      measured IP1 is in excellent agreement with the value of 4.963(15) electronvolts
      predicted here by state-of-the-art relativistic calculations. The present work
      provides a reliable benchmark for theoretical calculations and also opens the way
      for IP1 measurements of superheavy elements (that is, transactinides) on an atom
      at-a-time scale.

PMID- 25855458
TI  - A primordial origin for the compositional similarity between the Earth and the
      Moon.
AB  - Most of the properties of the Earth-Moon system can be explained by a collision
      between a planetary embryo (giant impactor) and the growing Earth late in the
      accretion process. Simulations show that most of the material that eventually
      aggregates to form the Moon originates from the impactor. However, analysis of
      the terrestrial and lunar isotopic compositions show them to be highly similar.
      In contrast, the compositions of other Solar System bodies are significantly
      different from those of the Earth and Moon, suggesting that different Solar
      System bodies have distinct compositions. This challenges the giant impact
      scenario, because the Moon-forming impactor must then also be thought to have a
      composition different from that of the proto-Earth. Here we track the feeding
      zones of growing planets in a suite of simulations of planetary accretion, to
      measure the composition of Moon-forming impactors. We find that different planets
      formed in the same simulation have distinct compositions, but the compositions of
      giant impactors are statistically more similar to the planets they impact. A
      large fraction of planet-impactor pairs have almost identical compositions. Thus,
      the similarity in composition between the Earth and Moon could be a natural
      consequence of a late giant impact. 

PMID- 25855459
TI  - Repeated ER-endosome contacts promote endosome translocation and neurite
      outgrowth.
AB  - The main organelles of the secretory and endocytic pathways--the endoplasmic
      reticulum (ER) and endosomes, respectively--are connected through contact sites
      whose numbers increase as endosomes mature. One function of such sites is to
      enable dephosphorylation of the cytosolic tails of endosomal signalling receptors
      by an ER-associated phosphatase, whereas others serve to negatively control the
      association of endosomes with the minus-end-directed microtubule motor dynein or
      mediate endosome fission. Cholesterol transfer and Ca(2+) exchange have been
      proposed as additional functions of such sites. However, the compositions,
      activities and regulations of ER-endosome contact sites remain incompletely
      understood. Here we show in human and rat cell lines that protrudin, an ER
      protein that promotes protrusion and neurite outgrowth, forms contact sites with
      late endosomes (LEs) via coincident detection of the small GTPase RAB7 and
      phosphatidylinositol 3-phosphate (PtdIns(3)P). These contact sites mediate
      transfer of the microtubule motor kinesin 1 from protrudin to the motor adaptor
      FYCO1 on LEs. Repeated LE-ER contacts promote microtubule-dependent translocation
      of LEs to the cell periphery and subsequent synaptotagmin-VII-dependent fusion
      with the plasma membrane. Such fusion induces outgrowth of protrusions and
      neurites, which requires the abilities of protrudin and FYCO1 to interact with
      LEs and kinesin 1. Thus, protrudin-containing ER-LE contact sites are platforms
      for kinesin-1 loading onto LEs, and kinesin-1-mediated translocation of LEs to
      the plasma membrane, fuelled by repeated ER contacts, promotes protrusion and
      neurite outgrowth.

PMID- 25855461
TI  - Pharmacological treatment for pain in Guillain-Barre syndrome.
AB  - BACKGROUND: Pain in Guillain-Barre syndrome (GBS) is common, yet it is often
      under recognised and poorly managed. In recent years, a variety of
      pharmacological treatment options have been investigated in clinical trials for
      people with GBS-associated pain. This is an updated version of the original
      Cochrane review published in Issue 10, 2013. OBJECTIVES: To assess the efficacy
      and safety of pharmacological treatments for various pain symptoms associated
      with GBS, during both the acute and convalescent (three months or more after
      onset) phases of GBS. SEARCH METHODS: On 3 November 2014, we searched the
      Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE and
      EMBASE. In addition, we searched ClinicalTrials.gov and the World Health
      Organization (WHO) International Clinical Trials Registry Platform. SELECTION
      CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs in
      participants with confirmed GBS, with pain assessment as either the primary or
      secondary outcome. For cross-over trials, an adequate washout period between
      phases was required for inclusion. DATA COLLECTION AND ANALYSIS: Two review
      authors independently screened the titles and abstracts of identified records,
      selected studies for inclusion, extracted eligible data, cross-checked the data
      for accuracy and assessed the risk of bias of each study. MAIN RESULTS: Three
      short-term RCTs, which enrolled 277 randomised participants with acute phase GBS,
      were included. Risk of bias in the included studies was generally unclear due to
      insufficient information. None of the included studies reported the primary
      outcome selected for this review, which was number of patients with self reported
      pain relief of 50% or greater. One small study investigated seven-day regimens of
      gabapentin versus placebo. Pain was rated on a scale from 0 (no pain) to 10
      (maximum pain). Amongst the 18 participants, significantly lower mean pain scores
      were found at the endpoint (day 7) in the gabapentin phase compared to the
      endpoint of the placebo phase (mean difference -3.61, 95% CI -4.12 to -3.10)
      (very low quality evidence). For adverse events, no significant differences were
      found in the incidence of nausea (risk ratio (RR) 0.50, 95% CI 0.05 to 5.04) or
      constipation (RR 0.14, 95% CI 0.01 to 2.54). A second study enrolling 36
      participants compared gabapentin, carbamazepine and placebo, all administered
      over seven days. Participants in the gabapentin group had significantly lower
      median pain scores on all treatment days in comparison to the placebo and
      carbamazepine groups (P < 0.05). There were no statistically significant
      differences in the median pain scores between the carbamazepine and placebo
      groups from day 1 to day 3, but from day 4 until the end of the study
      significantly lower median pain scores were noted in the carbamazepine group (P <
      0.05) (very low quality evidence). There were no adverse effects of gabapentin or
      carbamazepine reported, other than sedation. One large RCT (223 participants, all
      also treated with intravenous immunoglobulin), compared a five-day course of
      methylprednisolone with placebo and found no statistically significant
      differences in number of participants developing pain (RR 0.89, 95% CI 0.68 to
      1.16), number of participants with decreased pain (RR 0.95, 95% CI 0.63 to 1.42)
      or number of participants with increased pain (RR 0.85, 95% CI 0.52 to 1.41) (low
      quality evidence). The study did not report whether there were any adverse
      events. AUTHORS' CONCLUSIONS: Since the last version of this review we found no
      new studies. While management of pain in GBS is essential and pharmacotherapy is
      widely accepted as being an important component of treatment, this review does
      not provide sufficient evidence to support the use of any pharmacological
      intervention in people with pain in GBS. Although reductions in pain severity
      were found when comparing gabapentin and carbamazepine with placebo, the evidence
      was limited and its quality very low. Larger, well-designed RCTs are required to
      further investigate the efficacy and safety of potential interventions for
      patients with pain in GBS. Additionally, interventions for pain in the
      convalescent phase of GBS should be investigated.

PMID- 25855462
TI  - [Remove polyps and discard. Way or wrong way?].

PMID- 25855463
TI  - Reliability of Oscillometric Blood Pressure Monitoring in Atrial Fibrillation
      Patients Admitted for Electric Cardioversion.
AB  - The reliability of automated oscillometric blood pressure (BP) monitors in atrial
      fibrillation (AF) has been poorly investigated, only comparing different patients
      with AF and sinus rhythm (SR), and is a method influenced by individual
      characteristics. This study compared the reliability of the oscillometric device
      A&D TM-2430 (A&D Company, Tokyo, Japan) with that of a mercury sphygmomanometer
      in AF patients whose SR was restored after electric cardioversion (ECV). Three
      consecutive BP measurements were obtained on the day before and about 30 days
      after ECV in stable treatment conditions. Of the 100 patients studied, 63
      reported an SR at follow-up, with a significant increase in systolic BP and a
      significant decrease in diastolic BP according to both devices. There were no
      significant differences between the systolic and diastolic biases before and
      after ECV using Bland Altman analysis (P > .05 each). The oscillometric device
      analyzed, using three repeated measurements, is reliable in measuring BP in AF
      patients.

PMID- 25855464
TI  - Regional aortic distensibility and its relationship with age and aortic stenosis:
      a computed tomography study.
AB  - Aortic distensibility (AD) decreases with age and increased aortic stiffness is
      independently associated with adverse cardiovascular outcomes. The association of
      severe aortic stenosis (AS) with AD in different aortic regions has not been
      evaluated. Elderly subjects with severe AS and a cohort of patients without AS of
      similar age were studied. Proximal aortic cross-sectional-area changes during the
      cardiac cycle were determined using retrospective-ECG-gating on 128-detector row
      computed-tomography. Using oscillometric-brachial-blood-pressure measurements,
      the AD at the ascending-aorta (AA), proximal-descending-aorta (PDA) and distal
      descending-aorta (DDA) was determined. Linear mixed effects modelling was used to
      determine the association of age and aortic stenosis on regional AD. 102 patients
      were evaluated: 36 AS patients (70-85 years), 24 AS patients (>85 years) and 42
      patients without AS (9 patients <50 years, 20 patients between 51-70 years and 13
      patients 70-85 years). When comparing patients 70-85 years, AA distensibility was
      significantly lower in those with AS compared to those without AS (0.9 +/- 0.9
      vs. 1.4 +/- 1.1, P = 0.03) while there was no difference in the PDA (1.0 +/- 1.1
      vs. 1.0 +/- 1.2, P = 0.26) and DDA (1.1 +/- 1.2 vs. 1.2 +/- 0.8, P = 0.97). In
      patients without AS, AD decreased with age in all aortic regions (P < 0.001). The
      AA in patients <50 years were the most distensible compared to other aortic
      regions. There is regional variation in aortic distensibility with aging.
      Patients with aortic stenosis demonstrated regional differences in aortic
      distensibility with lower distensibility demonstrated in the proximal ascending
      aorta compared to an age-matched cohort.

PMID- 25855466
TI  - Transverse dental arch relationship at 9 and 12 years in children with unilateral
      cleft lip and palate treated with infant orthopedics: a randomized clinical trial
      (DUTCHCLEFT).
AB  - OBJECTIVE: A long-term evaluation to assess the transverse dental arch
      relationships at 9 and 12 years of age in unilateral cleft lip and palate treated
      with or without infant orthopedics (IO). The hypothesis is that IO has no effect
      on the transverse dental arch relationship. MATERIAL AND METHODS: A prospective
      two-arm randomized controlled trial (DUTCHCLEFT) in three academic cleft palate
      centers (Amsterdam, Nijmegen and Rotterdam, the Netherlands). Fifty-four children
      with complete unilateral cleft lip and palate and no other malformations were
      enrolled in this evaluation. One group wore passive maxillary plates (IO+) during
      the first year of life, and the other group did not (IO-). Until the age of 1.5,
      all other interventions were the same. Hard palate was closed simultaneously with
      bone grafting according to protocol of all teams. Orthodontic treatment was
      performed when indicated. The transverse dental arch relationship was assessed on
      dental casts using the modified Huddart/Bodenham score to measure the maxillary
      arch constriction at 9 and 12 years of age. RESULTS: No significant differences
      were found between the IO+ and IO- groups. Differences between the centers
      increased from 9 to 12 years of age. CONCLUSIONS: Transverse dental arch
      relationships at 9 and 12 years of age do not differ between children with UCLP
      treated with or without IO. CLINICAL RELEVANCE: There is no orthodontic need to
      perform IO as applied in this study in children with UCLP.

PMID- 25855467
TI  - Effects of high-energy ball-milling on injectability and strength of beta
      tricalcium-phosphate cement.
AB  - Calcium phosphate cement (CPC) offers many advantages as a bone-substitution
      material. The objective of this study is to develop a new CPC that simultaneously
      exhibits fine injectability, a short setting time, and high strength. beta
      tricalcium phosphate (beta-TCP, control) powder was ball-milled for 24h to
      produce a new cement powder. The modified beta-TCP after 24h milling (mbeta-TCP
      24h) exhibited excellent injectability even 1h after mixing. The mechanical
      properties of the set cement (compact) were evaluated using compressive strength
      (CS) and diametral tensile strength (DTS) testing. The CS and DTS values of the
      mbeta-TCP-24h compacts were 8.02MPa and 2.62MPa, respectively, at 5h after
      mixing, and were 49.6MPa and 7.9MPa, respectively, at 2 weeks after mixing. All
      the CS and DTS values of the mbeta-TCP-24h compacts were significantly higher
      than those of the control for the same duration after mixing. These results
      suggest that the mechano-chemically modified beta-TCP powder dissolves rapidly
      and accelerates hydroxyapatite precipitation, which successfully shortens the
      cement setting time and enhances the strength. This study supports that mbeta-TCP
      24h is a promising candidate for use in injectable CPCs with improved strength. 

PMID- 25855468
TI  - Unraveling the structural features of organic aerosols by NMR spectroscopy: a
      review.
AB  - Our limited understanding of the effect of organic aerosols (OAs) on the climate
      and human health is largely because of the vast array of formation processes and
      sources that produce a multitude of molecular structures and physical properties.
      The need to unravel the enormous complexity and heterogeneity of OAs and thus
      understand their effects on the climate and human health has led to the
      development of different off-line methods based on the use of advanced analytical
      techniques. Within this context, nuclear magnetic resonance (NMR) spectroscopy
      has become essential for acquiring detailed structural characterization of the
      complex natural organic matter contained in atmospheric aerosols. In this
      article, we present a critical review on the application of NMR spectroscopy in
      OAs (primary and secondary) studies, focusing mainly on the water-soluble organic
      fraction, and how NMR has impacted our knowledge on atmospheric organic matter. A
      major emphasis is given on the wealth of chemical information that solid-state
      and multi-dimensional solution-state NMR can provide, including the sources,
      formation pathways, seasonal, and regional characterization of atmospheric OAs.
      Finally, major challenges are discussed and recommendations for future research
      directions are proposed.

PMID- 25855469
TI  - Prevalence of excessive sleepiness is higher whereas insomnia is lower with
      greater severity of obstructive sleep apnea.
AB  - PURPOSE: The objective of the present study was to investigate the prevalence of
      insomnia and excessive sleepiness in relation to the presence and severity of
      obstructive sleep apnea (OSA). METHODS: The sample consisted of patients referred
      to a university hospital on suspicion of OSA. In total, 1115 patients with mean
      age of 48 years were studied. Insomnia (Bergen Insomnia Scale) and excessive
      sleepiness (Epworth Sleepiness Scale) were diagnosed using validated
      questionnaires. The insomnia scale permits diagnosing insomnia using both old and
      new (from 2014) criteria. OSA was diagnosed and categorized based on a standard
      respiratory polygraphic sleep study using a type 3 portable monitor. RESULTS: OSA
      was diagnosed in 59.4 % of the referred patients. The prevalence of excessive
      sleepiness was higher with greater severity of OSA: 40.5 % in the patients
      without OSA (apnea-hypopnea index (AHI) <5), 46.5 % in mild OSA (AHI 5-14.9),
      52.0 % in moderate OSA (AHI 15-29.9), and 58.0 % in severe OSA (AHI 30 or above).
      In contrast, the prevalence of insomnia using the 2014 diagnostic criteria showed
      an opposing prevalence: 54.2 % no OSA, 54.9 % mild OSA, 48.5 % moderate OSA, and
      44.6 % severe OSA. Logistic and linear regression analyses showed that sleepiness
      was positively associated whereas insomnia was negatively associated with OSA
      severity and AHI. CONCLUSIONS: Both excessive sleepiness and insomnia were seen
      in high proportions of the patients referred on suspicion of OSA. Excessive
      sleepiness was higher whereas insomnia was lower with greater OSA severity.

PMID- 25855470
TI  - The relationships between the clinical and polysomnographic findings and the
      olfactory function in patients with obstructive sleep apnea syndrome.
AB  - PURPOSE: This study aimed to investigate the relationships between the clinical
      and polysomnographic findings and the olfactory test results in patients with
      obstructive sleep apnea syndrome (OSAS). METHODS: Four groups were established:
      non-snoring controls (group 1), non-apneic snorers (group 2), mild-moderate OSAS
      (group 3), and severe OSAS (group 4). The polysomnographic findings,
      otorhinolaryngologic findings, Epworth Sleepiness Scale (ESS), and Sniffin'
      Sticks olfactory test results of the four groups were compared. The relationships
      between the clinical data and the olfactory parameters were evaluated. RESULTS:
      Group 4 had the worst odor identification and discrimination scores. Non-apneic
      snorers also had worse odor parameters compared with the non-snorer controls. A
      significant negative correlation was found among the ESS, apnea-hypopnea index
      (AHI), mean arterial oxygen saturation, and odor identification and
      discrimination. Significant negative correlations were found between the tongue
      and tongue base sizes and among all olfactory parameters. CONCLUSION: Our study
      revealed olfactory dysfunction in patients with OSAS. A strong negative
      correlation between the olfactory parameters and the severity of sleep apnea was
      also found. Olfactory tests may be used to predict the presence and severity of
      OSAS in the future.

PMID- 25855471
TI  - 2,3-Oxidosqualene cyclase protects liver cells from the injury of intermittent
      hypoxia by regulating lipid metabolism.
AB  - PURPOSE: 2,3-Oxidosqualene cyclase (OSC), an important enzyme of cholesterol
      biosynthesis, catalyzes the highly selective cyclization of 2,3-monoepoxysqualene
      to lanosterol. Intermittent hypoxia (IH) is a hallmark feature in obstructive
      sleep apnea (OSA) which is increasingly recognized as an independent risk factor
      for liver injury. The aim of this study was to determine the effect of IH on OSC
      expression and evaluate the role of OSC in the IH-induced apoptosis in hepatic
      cell line human liver cell (HL-02). METHODS: HL-02 cells were exposed to normoxia
      or IH. Cell Counting Kit-8 (CCK-8) assay was used to value cell proliferation,
      and flow cytometry was used to determine cell apoptosis. The expression of OSC
      messenger RNA (mRNA) was evaluated by quantitative real-time PCR, and the
      expression of OSC protein was determined by Western blot. To further investigate
      the function of OSC in IH-induced apoptosis, oxidosqualene cyclase-enhanced green
      fluorescence protein (OSC-EGFP) plasmid was constructed to over-express OSC
      protein. Triglyceride content in HL-02 cells was analyzed by oil red staining or
      Triglyceride Quantification Kit. RESULTS: We found that IH inhibited HL-02 cell
      proliferation and accelerated cell apoptosis. IH decreased OSC expression, and
      over-expression of OSC could protect HL-02 cells against the IH-induced hepatic
      cell injury. Moreover, over-expression of OSC could attenuate IH-induced cellular
      triglyceride accumulation. CONCLUSIONS: These findings suggest that OSC are
      involved in IH-induced hepatic cell injury. These results may contribute to the
      further understanding of the mechanism underlying the liver injury in OSA
      patients.

PMID- 25855472
TI  - Insomnia and excessive daytime sleepiness in obstructive sleep apnea: only
      different clinical phenotypes?

PMID- 25855473
TI  - Functional analysis of optineurin and some of its disease-associated mutants.
AB  - Optineurin is a multifunctional protein involved in a variety of cellular
      functions such as protein trafficking by vesicles, autophagy, and signal
      transduction. Certain mutations in optineurin (gene OPTN) are associated with
      neurodegenerative diseases like glaucoma and amyotrophic lateral sclerosis (ALS).
      Optineurin is also seen in pathological structures present in several other
      neurodegenerative diseases. In glaucoma, loss of vision occurs due to progressive
      degeneration of retinal ganglion cells, and perhaps loss of photoreceptor cone
      cells as well. Most of the glaucoma-associated mutations of optineurin are
      heterozygous missense mutations, whereas the ALS-associated mutations include
      deletion, truncation, and missense mutations. Optineurin mediates its functions
      by interacting with various proteins, often acting as an adaptor to provide a
      link between two or more proteins. Disease-causing mutations alter these
      interactions leading to functional defects in membrane vesicle trafficking,
      autophagy, signaling, aggregate formation, and other processes. Some of these
      functional defects, caused by glaucoma-associated mutants of optineurin, led to
      retinal cell death mediated by apoptosis and therefore may contribute to
      pathogenesis directly. Other mutations are likely to cause glaucoma by indirect
      mechanisms involving other cell types. Mechanisms of ALS pathogenesis by
      optineurin mutations are yet to be investigated in detail; however, some ALS
      associated mutants cause defects in signaling, autophagy, and ubiquitin binding,
      which might contribute to pathogenesis.

PMID- 25855474
TI  - Clinical outcome of stand-alone ALIF compared to posterior instrumentation for
      degenerative disc disease: A pilot study and a literature review.
AB  - The objective of the article was to: a) present results from a case cohort pilot
      study comparing stand-alone ALIF and TLIF and, b) review the literature on
      studies comparing the clinical outcome of stand-alone ALIF with posterior
      instrumentation including TLIF or PLIF, in patients with disabling low back pain
      resulting from degenerative disc disease. ALIF surgery has previously been linked
      with certain high risk complications and unfavorable long term fusion results.
      Newer studies suggest that stand-alone ALIF can possibly be advantageous compared
      to other types of posterior instrumented interbody fusion for a selected group of
      DDD patients. The methods and material consisted of a cohort pilot study of
      patients, with DDD treated with stand-alone ALIF or TLIF followed by a literature
      review conducted through a comprehensive PubMed database search of the English
      literature. Studies comparing stand-alone ALIF with posterior instrumented
      interbody fusion were selected and reviewed. Results from the pilot study, n =
      21, showed a reduced perioperative blood loss, shorter operative time and a trend
      towards better pain reduction and decreased use of opioid analgesics in patients
      undergoing stand-alone ALIF compared to posterior instrumented fusion with TLIF.
      The literature review included three studies, n = 630. All three studies were
      retrospective cohort studies. The average patient follow-up was 2-years but with
      heterogeneous selected outcomes. Two of three articles documented significant
      advantages when using stand-alone ALIF on outcomes such as ODI, VAS, surgical
      time, blood loss and patient satisfaction. No study found stand-alone ALIF
      inferior in chosen outcomes including fusion. In conclusion the pilot study and
      the literature review, finds similar clinical outcomes and fusion rates after
      stand-alone ALIF and posterior interbody fusion. Stand-alone ALIF was associated
      with a shorter duration of surgery, less perioperative blood loss and a faster
      improvement post-operatively. Therefore stand-alone ALIF is a viable and
      important surgical option, which could be considered first choice as surgical
      treatment.

PMID- 25855475
TI  - Health economics and outcomes methods in risk-based decision-making for blood
      safety.
AB  - Analytical methods appropriate for health economic assessments of transfusion
      safety interventions have not previously been described in ways that facilitate
      their use. Within the context of risk-based decision-making (RBDM), health
      economics can be important for optimizing decisions among competing
      interventions. The objective of this review is to address key considerations and
      limitations of current methods as they apply to blood safety. Because a voluntary
      blood supply is an example of a public good, analyses should be conducted from
      the societal perspective when possible. Two primary study designs are recommended
      for most blood safety intervention assessments: budget impact analysis (BIA),
      which measures the cost to implement an intervention both to the blood operator
      but also in a broader context, and cost-utility analysis (CUA), which measures
      the ratio between costs and health gain achieved, in terms of reduced morbidity
      and mortality, by use of an intervention. These analyses often have important
      limitations because data that reflect specific aspects, for example, blood
      recipient population characteristics or complication rates, are not available.
      Sensitivity analyses play an important role. The impact of various uncertain
      factors can be studied conjointly in probabilistic sensitivity analyses. The use
      of BIA and CUA together provides a comprehensive assessment of the costs and
      benefits from implementing (or not) specific interventions. RBDM is multifaceted
      and impacts a broad spectrum of stakeholders. Gathering and analyzing health
      economic evidence as part of the RBDM process enhances the quality, completeness,
      and transparency of decision-making. 

PMID- 25855476
TI  - The role of parvovirus B19 and the immune response in the pathogenesis of acute
      leukemia.
AB  - In this article, we review the evidence suggesting a possible role for B19 virus
      in the pathogenesis of a subset of cases of acute leukemia. Human parvovirus B19
      infection may complicate the clinical course of patients with acute leukemia and
      may also precede the development of acute leukemia by up to 180 days. Parvovirus
      B19 targets erythroblasts in the bone marrow and may cause aplastic crisis in
      patients with shortened-red cell survival. Aplastic crisis represents a prodrome
      of acute lymphoblastic leukemia in 2% patients. There is a significant overlap
      between those HLA classes I and II alleles that are associated with a vigorous
      immune response and development of symptoms during B19 infection and those HLA
      alleles that predispose to development of acute leukemia. Acute symptomatic B19
      infection is associated with low circulating IL-10 consistent with a vigorous
      immune response; deficient IL-10 production at birth was recently found to be
      associated with subsequent development of acute leukemia. Anti-B19 IgG has been
      associated with a particular profile of methylation of human cancer genes in
      patients with acute leukemia, suggesting an additional hit and run mechanism. The
      proposed role for parvovirus B19 in the pathogenesis of acute leukemia fits well
      with the delayed infection hypothesis and with the two-step mutation model, which
      describes carriage of the first mutation prior to birth, followed by suppression
      of hematopoiesis, which allows rapid proliferation of cells harboring the first
      mutation, acquisition of a second activating mutation, and expansion of cells
      carrying both mutations, resulting in acute leukemia.

PMID- 25855478
TI  - Sequence Programmable Peptoid Polymers for Diverse Materials Applications.
AB  - Polymer sequence programmability is required for the diverse structures and
      complex properties that are achieved by native biological polymers, but efforts
      towards controlling the sequence of synthetic polymers are, by comparison, still
      in their infancy. Traditional polymers provide robust and chemically diverse
      materials, but synthetic control over their monomer sequences is limited. The
      modular and step-wise synthesis of peptoid polymers, on the other hand, allows
      for precise control over the monomer sequences, affording opportunities for these
      chains to fold into well-defined nanostructures. Hundreds of different side
      chains have been incorporated into peptoid polymers using efficient reaction
      chemistry, allowing for a seemingly infinite variety of possible synthetically
      accessible polymer sequences. Combinatorial discovery techniques have allowed the
      identification of functional polymers within large libraries of peptoids, and
      newly developed theoretical modeling tools specifically adapted for peptoids
      enable the future design of polymers with desired functions. Work towards
      controlling the three-dimensional structure of peptoids, from the conformation of
      the amide bond to the formation of protein-like tertiary structure, has and will
      continue to enable the construction of tunable and innovative nanomaterials that
      bridge the gap between natural and synthetic polymers. 

PMID- 25855477
TI  - Estrogen Receptor Alpha as a Mediator of Life-History Trade-offs.
AB  - Trade-offs between competitive and parental strategies often are mediated by sex
      steroids. The mechanisms underlying steroid signaling and metabolism may
      therefore serve as targets of disruptive selection that leads to alternative
      behavioral phenotypes. White-throated sparrows exhibit two color morphs that
      differ in both competitive and parental behavior; white-striped (WS) birds engage
      in more territorial singing, whereas tan-striped (TS) birds provision nestlings
      more often. Although WS birds have higher levels of plasma testosterone (T) and
      estradiol than do TS birds, experimental equalization of these hormones does not
      abolish morph differences in singing. Neural sensitivity to sex steroids may
      differ between the morphs because the gene for estrogen receptor alpha (ERalpha)
      has been captured by a chromosomal rearrangement found only in the WS birds. We
      recently showed that expression of this gene differs between the morphs and may
      drive the behavioral polymorphism. First, the ERalpha promoter region contains
      fixed polymorphisms that affect transcription efficiency in vitro. Second, in a
      free-living population, local expression of ERalpha depends strongly on morph and
      predicts both territorial singing and parental provisioning. Differential ERalpha
      expression is particularly striking in the medial amygdala; WS birds have three
      times more ERalpha mRNA than do TS birds. This difference persists during the non
      breeding season and is unaffected by exogenous T treatment. Finally, preliminary
      data generated by RNA-seq confirm that ERalpha expression in MeA is both
      differentially expressed and correlated with territorial singing. Together, these
      results suggest that ERalpha may be a target of disruptive selection that leads
      to alternative behavioral strategies. Our future directions include a more
      detailed analysis of the ERalpha promoter regions to determine the molecular
      basis of differential expression as well as gene network analyses to identify
      genes connected to ERalpha. 

PMID- 25855479
TI  - Reductions in Use of Colchicine after FDA Enforcement of Market Exclusivity in a
      Commercially Insured Population.
AB  - BACKGROUND: A brand-name version of colchicine (Colcrys) was introduced after its
      manufacturer conducted a clinical trial in acute gout patients, leading to higher
      prices for this drug. OBJECTIVE: We analyzed the impact of the new single-source
      colchicine product on prescribing and patient health spending as well as
      incidence rates of potentially dangerous concomitant use of clarithromycin and
      cyclosporine after formal FDA approval. DESIGN/PARTICIPANTS: We conducted a
      retrospective cohort study of UnitedHealth-affiliated enrollees newly diagnosed
      with gout or FMF. MAIN MEASURES: Among gout and FMF patients separately, we
      assessed linear trends in colchicine prescriptions, prescription drug costs, and
      total health care costs from 2009 to September 2010 (market exclusivity
      announced) compared to January 2011 (market exclusivity enforced) through 2012.
      Next, we estimated trends in co-prescription within 15 days of clarithromycin,
      azithromycin (indicated on the Colcrys label for use in place of clarithromycin),
      and cyclosporine. KEY RESULTS: Among gout patients, before Colcrys' market
      exclusivity, the odds of receiving colchicine within 30 days of gout diagnosis
      increased 1.4 %/month (OR: 1.014, 95 % CI: 1.011-1.018). Following FDA action,
      the odds decreased by 0.5 %/month (OR: 0.995, 95 % CI: 0.992-0.999) (p < 0.001).
      Similarly, among FMF patients, odds of initiating colchicine changed from an
      increase of 2.8 %/month to a decrease by 7.6 %/month (p = 0.01). Patients
      receiving colchicine experienced increases in average monthly prescription drug
      costs ($418 vs. $651, p < 0.001) and health care costs ($3,406 vs. $3,534, p <
      0.001). Incidence rates of colchicine/clarithromycin co-prescription before and
      after FDA action did not change, while co-prescription of colchicine/cyclosporine
      increased after introduction of Colcrys [-0.75 monthly change in patients (95 %
      CI: -1.07, -0.43) vs. 0.13 (95 % CI: -0.16, 0.42), p < 0.001]. CONCLUSIONS: The
      FDA's actions were associated with a reduction in colchicine initiation and an
      increase in patient spending. By contrast, we did not observe any association
      with improvements in avoidance of potentially dangerous co-prescriptions.

PMID- 25855480
TI  - "Not Unless It's a Life or Death Thing": A Qualitative Study of the Health Care
      Experiences of Adults Who Stutter.
AB  - BACKGROUND: For adults who stutter, communication difficulties can impact many
      spheres of life. Previous studies have not examined how stuttering might impact
      patient's experiences with the medical system. OBJECTIVE: Our objective was to
      understand the range and depth of experiences with the medical system among
      adults who stutter. DESIGN: This was a qualitative study using age-stratified
      focus groups. PARTICIPANTS: Sixteen adults who stutter were recruited at a
      national conference about stuttering. APPROACH: We conducted three focus groups.
      Participants also completed a written questionnaire about sociodemographic
      characteristics, health status, and the impact of stuttering on their life [using
      the St. Louis Inventory of Life Perspectives Scale (SL-ILP-S) Total Effect
      Score]. We analyzed data using an iterative, thematic analysis, with an inductive
      approach, at a semantic level. KEY RESULTS: Participants were mostly (75 %) male
      and resided throughout the United States. The mean SL-ILP-S Total Effect Score
      was 27.3, indicating that stuttering caused minimal concern in participants'
      lives. Despite this, we identified five themes that characterize ways in which
      stuttering affects interactions with the medical system. Participants described
      (1) discomfort speaking with office staff and physicians, which resulted in (2)
      avoiding health care interactions because of stuttering, and (3) relying on a
      third party to navigate the medical system. During visits with physicians,
      participants felt that (4) discussing stuttering with physicians required trust
      and rapport, and (5) speaking assertively with physicians required self
      acceptance of their stuttering. CONCLUSIONS: We identified ways in which
      stuttering affects medical interactions. These results highlight the need for
      increased awareness and training for medical staff and physicians when caring for
      persons who stutter. Future studies among diverse samples of stutterers can
      determine the effects of stuttering on medical interactions, and inform the
      development of interventions to provide high quality health care for adults who
      stutter.

PMID- 25855482
TI  - Shopping for Direct-to-Consumer Screening: Buyers and Clinicians Beware.

PMID- 25855481
TI  - An Unusual Case of Statin-Induced Myopathy: Anti-HMGCoA Necrotizing Autoimmune
      Myopathy.
AB  - Statins are some of the most widely prescribed medications, and though generally
      well tolerated, can lead to a self-limited myopathy in a minority of patients.
      Recently, these medications have been associated with a necrotizing autoimmune
      myopathy (NAM). Statin-associated NAM is characterized by irritable myopathy on
      electromyography (EMG) and muscle necrosis with minimal inflammation on muscle
      biopsy. The case presented is a 63-year-old woman who has continued elevation of
      creatine kinase (CK) after discontinuation of statin therapy. She has irritable
      myopathy on EMG and NAM is confirmed by muscle biopsy. She subsequently tests
      positive for an experimental anti-3-hydroxy-3-methylglutaryl-coenzyme A (anti
      HMGCoA) antibody that is found to be present in patients with statin-associated
      NAM. Though statin-associated NAM is a relatively rare entity, it is an important
      consideration for the general internist in patients who continue to have CK
      elevation and weakness after discontinuation of statin therapy. Continued
      research is necessary to better define statin-specific and dose-dependent risk,
      as well as optimal treatment for this condition.

PMID- 25855483
TI  - Topoisomerase-1 gene copy aberrations are frequent in patients with breast
      cancer.
AB  - Topoisomerase-1 (Top1) targeting drugs have shown promising efficacy in patients
      with metastatic breast cancer (BC). However, these drugs are rather toxic calling
      for development and validation of predictive biomarkers to increase the
      therapeutic index. As these drugs are targeting the Top1 protein and since no
      validated anti-Top1 antibodies for immunohistochemistry have been reported, we
      raised the hypothesis that TOP1 gene amplifications may serve as a proxy for the
      Top1 protein and thereby a biomarker of response to treatment with Top1
      inhibitors in BC. The aim was to determine the prevalence of TOP1 gene copy gain
      in BC. The prevalence of TOP1 gene copy gain was investigated by fluorescence in
      situ hybridization with a TOP1/CEN-20 probemix in normal breast tissue (N = 100)
      and in tissue from patients with metastatic BC in a discovery (N = 100) and a
      validation cohort (N = 205). As amplification of 20q including CEN-20 is common
      in BC a TOP1/CEN-2 probemix was applied to the validation cohort. More than 30%
      of the patients had gene copy numbers of >= 4 and ~20% of the patients had
      TOP1/CEN-20 ratios >= 1.5. The CEN-2 probe did not add any information. Gain of
      the TOP1 gene appears to be common in BC making the gene a potential biomarker
      for response to treatment with Top1 inhibitors. As 20q amplification is a common
      finding in BC and as no other suitable reference gene has yet been identified,
      TOP1 copy number may be a more valid method of detecting gain than using a
      gene/centromere ratio. 

PMID- 25855484
TI  - Transition considerations for extended half-life factor products.

PMID- 25855486
TI  - Erratum to: Maternal inheritance of mitochondrial genomes and complex inheritance
      of chloroplast genomes in Actinidia Lind.: evidences from interspecific crosses.

PMID- 25855485
TI  - Genome-wide characterization and analysis of F-box protein-encoding genes in the
      Malus domestica genome.
AB  - The F-box protein family is a large family that is characterized by conserved F
      box domains of approximately 40-50 amino acids in the N-terminus. F-box proteins
      participate in diverse cellular processes, such as development of floral organs,
      signal transduction and response to stress, primarily as a component of the Skp1
      cullin-F-box (SCF) complex. In this study, using a global search of the apple
      genome, 517 F-box protein-encoding genes (F-box genes for short) were identified
      and further subdivided into 12 groups according to the characterization of known
      functional domains, which suggests the different potential functions or processes
      that they were involved in. Among these domains, the galactose oxidase domain was
      analyzed for the first time in plants, and this domain was present with or
      without the Kelch domain. The F-box genes were distributed in all 17 apple
      chromosomes with various densities and tended to form gene clusters. Spatial
      expression profile analysis revealed that F-box genes have organ-specific
      expression and are widely expressed in all organs. Proteins that contained the
      galactose oxidase domain were highly expressed in leaves, flowers and seeds. From
      a fruit ripening expression profile, 166 F-box genes were identified. The
      expressions of most of these genes changed little during maturation, but five of
      them increased significantly. Using qRT-PCR to examine the expression of F-box
      genes encoding proteins with domains related to stress, the results revealed that
      F-box proteins were up- or down-regulated, which suggests that F-box genes were
      involved in abiotic stress. The results of this study helped to elucidate the
      functions of F-box proteins, especially in Rosaceae plants.

PMID- 25855487
TI  - Inhibition of clot formation in deterministic lateral displacement arrays for
      processing large volumes of blood for rare cell capture.
AB  - Microfluidic deterministic lateral displacement (DLD) arrays have been applied
      for fractionation and analysis of cells in quantities of ~100 MUL of blood, with
      processing of larger quantities limited by clogging in the chip. In this paper,
      we (i) demonstrate that this clogging phenomenon is due to conventional platelet
      driven clot formation, (ii) identify and inhibit the two dominant biological
      mechanisms driving this process, and (iii) characterize how further reductions in
      clot formation can be achieved through higher flow rates and blood dilution.
      Following from these three advances, we demonstrate processing of 14 mL
      equivalent volume of undiluted whole blood through a single DLD array in 38
      minutes to harvest PC3 cancer cells with ~86% yield. It is possible to fit more
      than 10 such DLD arrays on a single chip, which would then provide the capability
      to process well over 100 mL of undiluted whole blood on a single chip in less
      than one hour. 

PMID- 25855488
TI  - Glucose and triglyceride excursions following a standardized meal in individuals
      with diabetes: ELSA-Brasil study.
AB  - OBJECTIVE: To assess glucose and triglyceride excursions 2 hours after the
      ingestion of a standardized meal and their associations with clinical
      characteristics and cardiovascular complications in individuals with diabetes.
      RESEARCH DESIGN AND METHODS: Blood samples of 898 subjects with diabetes were
      collected at fasting and 2 hours after a meal containing 455 kcal, 14 g of
      saturated fat and 47 g of carbohydrates. Self-reported morbidity, socio
      demographic characteristics and clinical measures were obtained by interview and
      exams performed at the baseline visit of the ELSA-Brasil cohort study. RESULTS:
      Median (interquartile range, IQR) for fasting glucose was 150.5 (123-198) mg/dL
      and for fasting triglycerides 140 (103-199) mg/dL. The median excursion for
      glucose was 45 (15-76) mg/dL and for triglycerides 26 (11-45) mg/dL. In multiple
      linear regression, a greater glucose excursion was associated with higher
      glycated hemoglobin (10.7, 95% CI 9.1-12.3 mg/dL), duration of diabetes (4.5; 2.6
      6.4 mg/dL, per 5 year increase), insulin use (44.4; 31.7-57.1 mg/dL), and age
      (6.1; 2.5-9.6 mg/dL, per 10 year increase); and with lower body mass index (-5.6;
      -8.4- -2.8 mg/dL, per 5 kg/m2 increase). In adjusted logistic regression models,
      a greater glucose excursion was marginally associated with the presence of
      cardiovascular comorbidities (coronary heart disease, myocardial infarction and
      angina) in those with obesity. CONCLUSIONS: A greater postprandial glycemic
      response to a small meal was positively associated with indicators of a decreased
      capacity for insulin secretion and negatively associated with obesity. No pattern
      of response was observed with a greater postprandial triglyceride excursion.

PMID- 25855490
TI  - Key elements for nourishing the translational research environment.
AB  - Translation in an academic environment requires a support system--people, goals,
      models, partnerships, and infrastructures--that will push promising basic science
      and technology projects forward into the clinic.

PMID- 25855489
TI  - Catalytic decarbonylation of biosourced substrates.
AB  - Linear alpha-olefins (LAO) are one of the main targets in the field of
      surfactants, lubricants, and polymers. With the depletion of petroleum resources,
      the production of LAO from renewable feedstocks has gained increasing interest in
      recent years. In the present study, we demonstrated that Ir catalysts were
      suitable to decarbonylate a wide range of biosourced substrates under rather mild
      conditions (160  degrees C, 5 h reaction time) in the presence of potassium
      iodide and acetic anhydride. The resulting LAO were obtained with good conversion
      and selectivity provided that the purity of the substrate, the nature of the
      ligand, and the amounts of the additives were controlled accurately. The
      catalytic system could be recovered efficiently by using a Kugelrohr distillation
      apparatus and recycled. 

PMID- 25855491
TI  - Spreading depression: epilepsy's wave of death.
AB  - Seizures may trigger spreading depression in brainstem nuclei, leading to central
      cardiorespiratory collapse and sudden unexpected death in epilepsy (Aiba and
      Noebels, this issue). 

PMID- 25855492
TI  - Spreading depolarization in the brainstem mediates sudden cardiorespiratory
      arrest in mouse SUDEP models.
AB  - Cardiorespiratory collapse after a seizure is the leading cause of sudden
      unexpected death in epilepsy (SUDEP) in young persons, but why only certain
      individuals are at risk is unknown. To identify a mechanism for this lethal
      cardiorespiratory failure, we examined whether genes linked to increased SUDEP
      risk lower the threshold for spreading depolarization (SD), a self-propagating
      depolarizing wave that silences neuronal networks. Mice carrying mutations in
      Kv1.1 potassium channels (-/-) and Scn1a sodium ion channels (+/R1407X) phenocopy
      many aspects of human SUDEP. In mutant, but not wild-type mice, seizures
      initiated by topical application of 4-aminopyridine to the cortex led to a slow,
      negative DC potential shift recorded in the dorsal medulla, a brainstem region
      that controls cardiorespiratory pacemaking. This irreversible event slowly
      depolarized cells and inactivated synaptic activity, producing cardiorespiratory
      arrest. Local initiation of SD in this region by potassium chloride
      microinjection also elicited electroencephalographic suppression, apnea,
      bradycardia, and asystole, similar to the events seen in monitored human SUDEP.
      In vitro study of brainstem slices confirmed that mutant mice had a lower
      threshold for SD elicited by metabolic substrate depletion and that immature mice
      were at greater risk than adults. Deletion of the gene encoding tau, which
      prolongs life in these mutants, also restored the normal SD threshold in Kv1.1
      mutant mouse brainstem. Thus, brainstem SD may be a critical threshold event
      linking seizures and SUDEP. 

PMID- 25855493
TI  - Vitamin D-dependent induction of cathelicidin in human macrophages results in
      cytotoxicity against high-grade B cell lymphoma.
AB  - Infiltration by macrophages represents a characteristic morphological hallmark in
      high-grade lymphatic malignancies such as Burkitt's lymphoma (BL). Although
      macrophages can, in principle, target neoplastic cells and mediate antibody
      dependent cellular cytotoxicity (ADCC), tumor-associated macrophages (TAMs)
      regularly fail to exert direct cytotoxic functions. The underlying mechanisms
      responsible for this observation remain unclear. We demonstrate that inflammatory
      M1 macrophages kill proliferating high-grade B cell lymphoma cells by releasing
      the antimicrobial peptide cathelicidin in a vitamin D-dependent fashion. We show
      that cathelicidin directly induces cell death by targeting mitochondria of BL
      cells. In contrast, anti-inflammatory M2 macrophages and M2-like TAMs in BL
      exhibit an altered vitamin D metabolism, resulting in a reduced production of
      cathelicidin and consequently in inability to lyse BL cells. However, treatment
      of M2 macrophages with the bioactive form of vitamin D, 1,25D3, or a vitamin D
      receptor agonist effectively induces cathelicidin production and triggers
      tumoricidal activity against BL cells. Furthermore, rituximab-mediated
      cytotoxicity of vitamin D-treated M2 macrophages is cathelicidin-dependent.
      Finally, vitamin D treatment of 25-hydroxyvitamin D (25D)-deficient volunteers in
      vivo or primary TAMs in vitro improves rituximab-mediated ADCC against B cell
      lymphoma cells. These data indicate that activation of the vitamin D signaling
      pathway activates antitumor activity of TAMs and improves the efficacy of ADCC. 

PMID- 25855494
TI  - Long-lasting stem cell-like memory CD8+ T cells with a naive-like profile upon
      yellow fever vaccination.
AB  - Efficient and persisting immune memory is essential for long-term protection from
      infectious and malignant diseases. The yellow fever (YF) vaccine is a live
      attenuated virus that mediates lifelong protection, with recent studies showing
      that the CD8(+) T cell response is particularly robust. Yet, limited data exist
      regarding the long-term CD8(+) T cell response, with no studies beyond 5 years
      after vaccination. We investigated 41 vaccinees, spanning 0.27 to 35 years after
      vaccination. YF-specific CD8(+) T cells were readily detected in almost all
      donors (38 of 41), with frequencies decreasing with time. As previously
      described, effector cells dominated the response early after vaccination. We
      detected a population of naive-like YF-specific CD8(+) T cells that was stably
      maintained for more than 25 years and was capable of self-renewal ex vivo. In
      depth analyses of markers and genome-wide mRNA profiling showed that naive-like
      YF-specific CD8(+) T cells in vaccinees (i) were distinct from genuine naive
      cells in unvaccinated donors, (ii) resembled the recently described stem cell
      like memory subset (Tscm), and (iii) among all differentiated subsets, had
      profiles closest to naive cells. Our findings reveal that CD8(+) Tscm are
      efficiently induced by a vaccine in humans, persist for decades, and preserve a
      naiveness-like profile. These data support YF vaccination as an optimal
      mechanistic model for the study of long-lasting memory CD8(+) T cells in humans. 

PMID- 25855495
TI  - Repurposing of the antihistamine chlorcyclizine and related compounds for
      treatment of hepatitis C virus infection.
AB  - Hepatitis C virus (HCV) infection affects an estimated 185 million people
      worldwide, with chronic infection often leading to liver cirrhosis and
      hepatocellular carcinoma. Although HCV is curable, there is an unmet need for the
      development of effective and affordable treatment options. Through a cell-based
      high-throughput screen, we identified chlorcyclizine HCl (CCZ), an over-the
      counter drug for allergy symptoms, as a potent inhibitor of HCV infection. CCZ
      inhibited HCV infection in human hepatoma cells and primary human hepatocytes.
      The mode of action of CCZ is mediated by inhibiting an early stage of HCV
      infection, probably targeting viral entry into host cells. The in vitro antiviral
      effect of CCZ was synergistic with other anti-HCV drugs, including ribavirin,
      interferon-alpha, telaprevir, boceprevir, sofosbuvir, daclatasvir, and
      cyclosporin A, without significant cytotoxicity, suggesting its potential in
      combination therapy of hepatitis C. In the mouse pharmacokinetic model, CCZ
      showed preferential liver distribution. In chimeric mice engrafted with primary
      human hepatocytes, CCZ significantly inhibited infection of HCV genotypes 1b and
      2a, without evidence of emergence of drug resistance, during 4 and 6 weeks of
      treatment, respectively. With its established clinical safety profile as an
      allergy medication, affordability, and a simple chemical structure for
      optimization, CCZ represents a promising candidate for drug repurposing and
      further development as an effective and accessible agent for treatment of HCV
      infection. 

PMID- 25855496
TI  - Postsurgical adjuvant or metastatic renal cell carcinoma therapy models reveal
      potent antitumor activity of metronomic oral topotecan with pazopanib.
AB  - Renal cell carcinoma (RCC), normally considered an intrinsically chemotherapy
      resistant cancer, is currently treated with targeted biologic therapies,
      including antiangiogenic tyrosine kinase inhibitors (TKIs), such as pazopanib.
      The efficacy of these agents is limited by both intrinsic and acquired
      resistance. Death is almost always due to advanced metastatic disease, a
      treatment circumstance seldom modeled in preclinical (mouse) drug testing.
      Similarly, therapy results using postsurgical adjuvant therapy models of
      microscopic disease have not been reported. Using in vivo selection and
      transfection of established human RCC cell lines (786-0 and SN12-PM6), we derived
      clonal luciferase-expressing variants capable of spontaneous metastasis from an
      orthotopic primary tumor to organs typical of clinical RCC, including bone,
      lungs, and brain. The bioluminescence and consistent metastatic spread of von
      Hippel-Lindau-wild type SN12-PM6-1 cells allowed for the establishment of
      perioperative therapy models of RCC. We report that the combination of daily low
      dose metronomic topotecan with pazopanib has highly potent antiprimary tumor as
      well as both postsurgical adjuvant and metastatic therapy efficacy despite lack
      of an antimetastatic effect of pazopanib monotherapy. The combination therapy
      resulted in sustained metastatic tumor cell dormancy, but tumor progression
      occurred upon treatment cessation. We also obtained evidence for a direct effect
      of pazopanib on RCC cells, resulting in increased intracellular concentration of
      topotecan. Our results suggest that this type of treatment combination should be
      considered for clinical evaluation in early- or late-stage metastatic disease,
      even for tumors seemingly intrinsically "resistant" to antiangiogenic TKIs or
      chemotherapy. 

PMID- 25855497
TI  - Targeting cancer-testis antigens in recurrent pediatric brain tumors.

PMID- 25855498
TI  - A tricarboxylated PtCl(terpyridine) derivative exhibiting pH-dependent
      photocatalytic activity for H2 evolution from water.
AB  - The first negatively charged PtCl(tpy) (tpy = 2,2':6',2''-terpyridine)
      derivative, formulated as Na2[PtCl(tctpy)].5H2O (tctpy = 2,2':6',2''-terpyridine
      4,4',4''-tricarboxylate), was prepared, characterized, and investigated in detail
      for its activity as a single-component photocatalyst that drives water reduction
      to H2 in the presence of a sacrificial electron donor (EDTA). This compound was
      confirmed to exist in its fully deprotonated form [PtCl(tctpy)](2-) in aqueous
      media at pH > 4.4. Despite its dianionic character, [PtCl(tctpy)](2-) was found
      to form a specific adduct with anionic EDTA (i.e., YH2(2-) and YH(3-), where YH4
      is a fully protonated form of EDTA), enabling reductive quenching of the triplet
      metal-to-ligand charge transfer excited state within the adduct, leading to
      subsequent electron transfer steps correlated with Pt(II)-catalyzed H2 evolution
      from water. Electrochemical studies also reveal that the compound exhibits a
      unique pH-dependent first reduction (i.e., tctpy-centered reduction), leading to
      our realization of the first example of a Pt(II)-based molecular system that
      photocatalyzes the H2 evolution reaction accompanied by a ligand-based proton
      coupled electron transfer (PCET) process.

PMID- 25855499
TI  - Drug discovery at the single molecule level: inhibition-in-solution assay of
      membrane-reconstituted beta-secretase using single-molecule imaging.
AB  - Inhibition-in-solution assays (ISA) employing surface-based biosensors such as
      surface plasmon resonance (SPR) are an effective screening approach in drug
      discovery. However, analysis of potent binders remains a significant hurdle due
      to limited sensitivity and accompanied depletion of the inhibiting compounds due
      to high protein concentrations needed for detectable binding signals. To overcome
      this limitation, we explored a microscopy-based single-molecule ISA compatible
      with liposome-reconstituted membrane proteins. Using a set of validated small
      molecule inhibitors against beta-secretase 1 (BACE1), the assay was benchmarked
      with respect to sensitivity and dynamic range against SPR. We demonstrate that
      the dynamic range of measurable affinities is greatly extended by more than 2
      orders of magnitude as compared to SPR, thus facilitating measurements of highly
      potent (Kd < nM) compounds. 

PMID- 25855500
TI  - Childhood intermittent exotropia from a different angle: does severity affect
      quality of life?
AB  - BACKGROUND: Few studies have explored the relationship between health-related
      quality of life (HRQOL) and clinical severity of childhood intermittent exotropia
      (IXT) measured by angle of deviation, control and stereoacuity. METHODS: Sixty
      eight consecutive children aged 5-17 years with childhood IXT who attended the
      paediatric eye clinic were recruited. One accompanying parent was recruited
      concurrently. Child, parent and proxy (parent about the child) HRQOL was measured
      using the IXT questionnaire (IXTQ). Angle of deviation, control and stereoacuity
      of the children were measured and correlated with IXTQ scores using Spearman's
      correlation coefficient and paired t test for differences in child and proxy IXTQ
      mean scores. RESULTS: The mean age of the children was 9.0+/-2.6 years. Child
      HRQOL was not correlated to any strabismus measurements. Poorer parent HRQOL was
      correlated with poorer distance control (surgery subscale, r=-0.24 p=0.049),
      poorer near control (surgery subscale, r=-0.30, p=0.013), poorer office near
      control (mean, r=-0.24, p=0.047; psychological subscale, r=-0.27, p=0.025;
      surgery subscale, r=-0.28, p=0.020) and larger angle of deviation (psychological
      subscale, r=-0.30, p=0.013). Poorer proxy HRQOL was correlated with poorer home
      control (r=-0.28, p=0.022) and larger angle of deviation (r=0.33, p=0.0061).
      CONCLUSIONS: It is difficult to predict child HRQOL based on clinical
      measurements. However, parent HRQOL tends to be worse with poorer control and
      larger angle of deviation. Perhaps HRQOL should be routinely assessed in clinic
      alongside clinical measurements in order to tailor management appropriately.

PMID- 25855501
TI  - Effect of femtosecond laser setting on visual performance after small-incision
      lenticule extraction for myopia.
AB  - AIM: To compare the effect of the two femtosecond laser settings on visual
      performance after small-incision lenticule extraction (SMILE) for myopia and
      myopic astigmatism. METHODS: Forty-four eyes of 22 consecutive patients who
      underwent SMILE with an energy level of 140 nJ (spot distance 3.0 um) in one eye,
      and with an energy level of 170 nJ (spot distance 4.5 um) in the other eye, the
      eyes being randomly assigned. Preoperatively, 1 week, and 1 and 3 months
      postoperatively, the values of the modulation transfer function (MTF) cutoff
      frequency, Strehl ratio, objective scattering index (OSI) and Optical Quality
      Analysis System (OQAS) values (OVs) for these eyes were quantitatively assessed
      using an Optical Quality Analysis System (Visiometrics). RESULTS: No significant
      differences were detected between the two groups in the visual and refractive
      outcomes, or in the MTF cutoff frequency, the Strehl ratio, the OSI, the OV 100%,
      the OV 20% or the OV 9% at any time point before or after surgery. CONCLUSIONS:
      SMILE with energy settings of 140 and 170 nJ was effective for the correction of
      myopia and myopic astigmatism. It is indicated that the differences in laser
      setting (140 nJ, spot distance 3.0 um vs 170 nJ, spot distance 4.5 um) did not
      significantly affect the optical quality including the intraocular scattering of
      eyes undergoing SMILE. CLINICAL TRIAL NUMBER: The protocol was registered with
      University Hospital Medical Information Network Clinical Trial Registry
      (UMIN000016241).

PMID- 25855502
TI  - Transconjunctival sutureless intrascleral intraocular lens fixation using
      intrascleral tunnels guided with catheter and 30-gauge needles.
AB  - We invented a new method for fixing an intraocular lens (IOL) in the scleral
      tunnel without using a wide conjunctival incision. Modified bent catheter needles
      were used to penetrate the IOL haptics through the sclerotomy sites. The IOL
      haptics were inserted into 30-guage (G) scleral tunnels guided by double 30-G
      needles piercing the sclera. All procedures were performed through the
      conjunctiva without wide incision. The procedure does not require special
      forceps, trocars or fibrin glue, only catheter and 30-G needles. The aid of an
      assistant was not required to support the IOL haptic. The procedures were easily
      learnt based on our previous method. As with other transconjunctival sutureless
      surgeries, patients feel less discomfort and the conjunctiva can be conserved for
      future glaucoma surgery. Complications included two cases of vitreous haemorrhage
      (16.7%), and one case each of postoperative hypotony, and iris capture (8.3%).
      Astigmatism induced by intraocular aberration was the same as we reported
      previously. Our method for fixing the IOL into the scleral tunnel is innovative,
      less expensive, less invasive and quick. This modified method is a good
      alternative for fixing IOL haptics into the sclera. 

PMID- 25855503
TI  - Drug courts as an alternative to probation for highly recidivistic drug
      offenders.

PMID- 25855504
TI  - Bilateral internal mammary artery fibromuscular dysplasia discovered upon
      evaluation for reconstructive breast surgery.

PMID- 25855505
TI  - Synthesis of 5,6-dihydro-4H-benzo[d]isoxazol-7-one and 5,6-dihydro-4H
      isoxazolo[5,4-c]pyridin-7-one derivatives as potential Hsp90 inhibitors.
AB  - A novel class of 5,6-dihydro-4H-benzo[d]isoxazol-7-ones and 5,6-dihydro-4H
      isoxazolo[5,4-c]pyridin-7-ones was designed, synthesized, and assayed to
      investigate the affinity toward Hsp90 protein. The synthetic route was based on a
      1,3-dipolar cycloaddition of nitriloxides, generated in situ from suitable
      benzaldoximes, with 2-bromocyclohex-2-enones or 3-bromo-5,6-dihydro-1H-pyridin-2
      ones. Whereas all the compounds bearing a benzamide group on the bicyclic
      scaffold were devoid of activity, the derivatives carrying a resorcinol-like
      fragment showed a remarkable inhibitory effect on Hsp90. Docking calculations
      were performed to investigate the orientation of the new compounds within the
      binding site of the enzyme. 

PMID- 25855506
TI  - HCBP6 Modulates Triglyceride Homeostasis in Hepatocytes Via the SREBP1c/FASN
      Pathway.
AB  - Hypertriglyceridemia leads to liver steatosis, cardiovascular disease, and type 2
      diabetes. Although HCBP6 (hepatitis C virus core-binding protein 6) was
      previously shown to be an HCV (hepatitis C virus) core-binding protein, its
      biological function remains unclear. Here, we demonstrate that HCBP6 negatively
      regulates intracellular triglyceride (TG) levels in hepatocytes. We found that
      bidirectional manipulation of hepatocyte HCBP6 expression by knockdown or
      overexpression results in increased or decreased TG accumulation, respectively.
      In addition, HCBP6 mRNA and protein levels exhibited significant time- and dose
      dependent increases in a cellular model of lipid-overload hepatic steatosis.
      Furthermore, TG levels are regulated by HCBP6-sterol regulatory element binding
      protein 1c (SREBP1c)-mediated fatty acid synthase (FASN) expression. We also
      demonstrate that HCBP6 mRNA and protein expression is inhibited by microRNA-122
      (miR-122), and miR-122 overexpression elicited more robust translational
      repression of luciferase activity driven by the full 3'-UTR of HCBP6. Taken
      together, our results provide new evidence that miR-122-regulated HCBP6 functions
      as a sensor protein to maintain intrahepatocyte TG levels.

PMID- 25855507
TI  - Influence of ADAMTS13 deficiency on venous thrombosis in mice.

PMID- 25855508
TI  - Evaluation of the transmission risk of foot-and-mouth disease in Japan.
AB  - The transmission risk of foot-and-mouth disease (FMD) in Japan was evaluated
      using a mathematical FMD transmission model. The distance-based transmission rate
      between farms, which was parameterized using the FMD epidemic data in 2010 in
      Japan, was used to calculate the local-level reproduction numbers-expected
      numbers of secondary infections caused by one infected farm-for all cattle and
      pig farms in the country, which were then visualized as a risk map. The risk map
      demonstrated the spatial heterogeneity of transmission risk in the country and
      identified risk areas with higher possibility of disease spread. This result
      suggests that, particularly in high-risk areas, it is important to prepare for
      the smooth and efficient implementation of control measures against FMD
      outbreaks.

PMID- 25855509
TI  - Suppression of influenza virus infection by the orf virus isolated in Taiwan.
AB  - Orf virus (ORFV), a member of parapoxvirus, is an enveloped virus with genome of
      double-stranded DNA. ORFV causes contagious pustular dermatitis or contagious
      ecthyma in sheep and goats worldwide. In general, detection of viral DNA and
      observing ORFV virion in tissues of afflicted animals are two methods commonly
      used for diagnosis of orf infection; however, isolation of the ORFV in cell
      culture using virus-containing tissue as inoculum is known to be difficult. In
      this work, the ORFV (Hoping strain) isolated in central Taiwan was successfully
      grown in cell culture. We further examined the biochemical characteristic of our
      isolate, including viral genotyping, viral mRNA and protein expression. By
      electron microscopy, one unique form of viral particle from ORFV infected
      cellular lysate was demonstrated in the negative-stained field. Moreover,
      immunomodulating and anti-influenza virus properties of this ORFV were
      investigated. ORFV stimulated human monocytes (THP-1) secreting proinflammatory
      cytokines IL-8 and TNF-alpha. And, pre-treatment of ORFV-infected cell medium
      prevents A549 cells from subsequent type A influenza virus (IAV) infection.
      Similarly, mice infected with ORFV via both intramuscular and subcutaneous routes
      at two days prior to IAV infection significantly decreased the replication of
      IAV. In summary, the results of a current study indicated our Hoping strain
      harbors the immune modulator property; with such a bio-adjuvanticity, we further
      proved that pre-exposure of ORFV protects animals from subsequent IAV infection.

PMID- 25855510
TI  - Rituximab-related late-onset neutropenia in patients with rheumatic diseases:
      successful re-challenge of the treatment.
AB  - BACKGROUND: We describe here 2 patients who developed late-onset neutropenia
      after Rituximab treatment. While this phenomenon is well described among patients
      suffering from hematological malignancies, such adverse effects are rare among
      patients with rheumatic diseases. CASE REPORT: Two patients, the first with
      rheumatoid arthritis and the second with granulomatosis with polyangiitis, were
      treated by Rituximab after all previous treatments failed. The patients developed
      late-onset neutropenia after several courses of treatment. The first patient,
      with symptomatic neutropenia, recovered after a single dose of granulocyte
      macrophage stimulating factor, and the second patient's neutrophils increased
      spontaneously. Both patients were retreated by rituximab in their scheduled time
      without further complications. CONCLUSIONS: Our case series is unique because the
      same phenomenon appeared in patients with different rheumatic diseases. This case
      series confirms the possibility of continuing the treatment without further
      adverse effects.

PMID- 25855511
TI  - Community-Sourced Intervention Programs: Review of Submissions in Response to a
      Statewide Call for "Promising Practices".
AB  - This study was initiated to add to the nascent literature on locally-grown
      intervention programs in the youth mental health, child welfare, and juvenile
      justice service sectors, many of which demonstrate practice-based or community
      defined evidence, but may not have been subjected to empirical evaluation.
      Characteristics of applications submitted in response to three public calls for
      additions to an inventory of research-supported intervention programs were
      reviewed on evidence for effectiveness, the use of key quality assurance (QA)
      elements (e.g., clearly specified training or integrity monitoring procedures),
      and cultural specificity. Findings indicate that four QA processes were
      identified in approximately half of all submissions: a specific initial training
      process, the existence of intervention integrity measures, routine outcome
      monitoring, and ongoing support post-training. An initial training process and
      integrity measurement were more commonly described among programs determined to
      have greater research evidence for their effectiveness. Overall, cultural
      elements were described relatively infrequently and most often reflected surface
      level program delivery characteristics (e.g., offering services in languages
      other than English). Discussion is focused on the alignment of submitted programs
      with the larger literatures focused on implementation science and cultural
      competence.

PMID- 25855512
TI  - Angiotensin AT2 receptor agonist prevents salt-sensitive hypertension in obese
      Zucker rats.
AB  - High-sodium intake is a risk factor for the pathogenesis of hypertension,
      especially in obesity. The present study is designed to investigate whether
      angiotensin type 2 receptor (AT2R) activation with selective agonist C21 prevents
      high-sodium diet (HSD)-induced hypertension in obese animals. Male obese rats
      were treated with AT2R agonist C21 (1 mg.kg(-1).day(-1), oral) while maintained
      on either normal-sodium diet (NSD; 0.4%) or HSD (4%) for 2 wk. Radiotelemetric
      recording showed a time-dependent increase in systolic blood pressure in HSD-fed
      obese rats, being maximal increase (~27 mmHg) at day 12 of the HSD regimen. C21
      treatment completely prevented the increase in blood pressure of HSD-fed rats.
      Compared with NSD controls, HSD-fed obese rats had greater natriuresis/diuresis
      and urinary levels of nitrates, and these parameters were further increased by
      C21 treatment. Also, C21 treatment improved glomerular filtration rate in HSD-fed
      rats. HSD-fed rats expressed higher level of cortical ANG II, which was reduced
      to 50% by C21 treatment. HSD feeding and/or C21 treatment had no effects on
      cortical renin activity and the expression of angiotensin-converting enzyme (ACE)
      and chymase, which are ANG II-producing enzymes. However, ANG(1-7) concentration
      and ACE2 activity in the renal cortex were reduced by HSD feeding, and C21
      treatment rescued both the parameters. Also, C21 treatment reduced the cortical
      expression of AT1R in HSD-fed rats, but had no effect of AT2R expression. We
      conclude that chronic treatment with the AT2R agonist C21 prevents salt-sensitive
      hypertension in obese rats, and a reduction in the renal ANG II/AT1R and enhanced
      ACE2/ANG(1-7) levels may play a potential role in this phenomenon.

PMID- 25855513
TI  - Modeling oxygen consumption in the proximal tubule: effects of NHE and SGLT2
      inhibition.
AB  - The objective of this study was to investigate how physiological,
      pharmacological, and pathological conditions that alter sodium reabsorption (TNa)
      in the proximal tubule affect oxygen consumption (QO2 ) and Na(+) transport
      efficiency (TNa/QO2 ). To do so, we expanded a mathematical model of solute
      transport in the proximal tubule of the rat kidney. The model represents
      compliant S1, S2, and S3 segments and accounts for their specific apical and
      basolateral transporters. Sodium is reabsorbed transcellularly, via apical
      Na(+)/H(+) exchangers (NHE) and Na(+)-glucose (SGLT) cotransporters, and
      paracellularly. Our results suggest that TNa/QO2 is 80% higher in S3 than in S1
      S2 segments, due to the greater contribution of the passive paracellular pathway
      to TNa in the former segment. Inhibition of NHE or Na-K-ATPase reduced TNa and
      QO2 , as well as Na(+) transport efficiency. SGLT2 inhibition also reduced
      proximal tubular TNa but increased QO2 ; these effects were relatively more
      pronounced in the S3 vs. the S1-S2 segments. Diabetes increased TNa and QO2 and
      reduced TNa/QO2 , owing mostly to hyperfiltration. Since SGLT2 inhibition lowers
      diabetic hyperfiltration, the net effect on TNa, QO2 , and Na(+) transport
      efficiency in the proximal tubule will largely depend on the individual extent to
      which glomerular filtration rate is lowered.

PMID- 25855515
TI  - Endothelial Function in Patients with Hematologic Malignancies Undergoing High
      Dose Chemotherapy Followed by Hematopoietic Stem Cell Transplantation.
AB  - The aim of the study was to examine endothelial function in patients with
      hematological malignancies treated with high-dose chemotherapy followed by
      hematopoietic stem cell transplantation. The studies were conducted on 43
      consecutive patients qualified for HSCT following high-dose chemotherapy based on
      the current standards. Then, due to exclusion criteria, a group of 38 patients
      were chosen for further investigations. Evaluation of endothelial function by
      means of flow-mediated dilatation (FMD) was conducted in patients with
      hematological malignancies before HSCT (test A) and after HSCT (test B). Brachial
      artery diameter (BAD) after occlusion, change in BAD and FMD were significantly
      lower after HSCT as compared to the results obtained before the transplantation
      (p < 0.05). The regression analysis indicated that administration of fludarabine
      and cytarabine, and also higher blood concentrations of creatinine represented
      risk factors for the impairment of endothelial function expressed as decreased
      FMD value. In patients with hematopoietic malignancies treated with HSCT,
      endothelial function assessed by the flow-mediated dilatation was impaired after
      chemotherapy and stem cell administration. 

PMID- 25855516
TI  - The Chronic Kidney Disease - Colonic Axis.
AB  - Chronic kidney disease (CKD) has long been known to cause significant
      gastrointestinal and colonic pathology. Recent advances in understanding of the
      role of colonic bacterial microbiome and its function and composition in health
      and disease have revealed previously unappreciated effects of CKD-associated
      colonic pathology on the development of uremic complications. CKD can result in
      profound changes in the microbiome composition and biosynthetic pattern, and the
      structure and function of the colon. Increases in bacteria that produce urease,
      uricase, p-cresol- and indole-forming enzymes and the depletion of bacteria that
      possess short chain fatty acid forming enzymes have been described in human and
      animal models. Disruption of the colonic epithelial tight junction in different
      animal models of CKD has been reported and is largely due to the conversion of
      luminal urea to ammonia by urease possessing bacteria. Together, these changes
      contribute to the pathogenesis of systemic inflammation and uremic toxicity by
      allowing the translocation of endotoxin and microbial fragments into the
      circulation. Additionally, colonic bacteria are the main source of several well
      known pro-inflammatory uremic toxins such as indoxyl sulfate, P-cresol sulfate.
      This review is intended to provide an overview of the effects of CKD on the
      colonic microbiome and the intestinal epithelial barrier structure and function
      and their role in the pathogenesis the systemic inflammation and uremic toxicity.

PMID- 25855514
TI  - Impact of a folic acid-enriched diet on urinary tract function in mice treated
      with testosterone and estradiol.
AB  - Aging men are susceptible to developing lower urinary tract symptoms, but the
      underlying etiology is unknown and the influence of dietary and environmental
      factors on them is unclear. We tested whether a folic acid-enriched diet changed
      urinary tract physiology and biology in control male mice and male mice with
      urinary dysfunction induced by exogenous testosterone and estradiol (T+E2), which
      mimics changing hormone levels in aging humans. T+E2 treatment increased mouse
      urine output, time between voiding events, and bladder capacity and compliance.
      Consumption of a folic acid-enriched diet moderated these changes without
      decreasing prostate wet weight or threshold voiding pressure. One potential
      mechanism for these changes involves water balance. T+E2 treatment increases
      plasma concentrations of anti-diuretic hormone, which is offset at least in part
      by a folic acid-enriched diet. Another potential mechanism involves neural
      control of micturition. The folic acid-enriched diet, fed to T+E2-treated mice,
      increased voiding frequency in response to intravesicular capsaicin infusion and
      increased mRNA abundance of the capsaicin-sensitive cation channel transient
      receptor potential vanilloid subfamily member 1 (Trpv1) in L6 and S1 dorsal root
      ganglia (DRG) neurons. T+E2 treatment and a folic acid-enriched diet also
      modified DNA methylation, which is capable of altering gene expression. We found
      the enriched diet increased global DNA methylation in dorsal and ventral prostate
      and L6 and S1 DRG. Our results are consistent with folic acid acting to slow or
      reverse T+E2-mediated alteration in urinary function in part by normalizing water
      balance and enhancing or preserving afferent neuronal function.

PMID- 25855517
TI  - MDM2 antagonist clinical response association with a gene expression signature in
      acute myeloid leukaemia.

PMID- 25855519
TI  - Thyroid hormone and astroglia: endocrine control of the neural environment.
AB  - Thyroid hormones (THs) play key roles in brain development and function. The lack
      of THs during childhood is associated with the impairment of several neuronal
      connections, cognitive deficits and mental disorders. Several lines of evidence
      point to astrocytes as TH targets and as mediators of TH action in the central
      nervous system; however, the mechanisms underlying these events are still not
      completely known. In this review, we focus on advances in our understanding of
      the effects of THs on astroglial cells and the impact of these effects on neurone
      astrocyte interactions. First, we discuss the signalling pathways involved in TH
      metabolism and the molecular mechanisms underlying TH receptor function. Then, we
      discuss data related to the effects of THs on astroglial cells, as well as
      studies regarding the generation of mutant TH receptor transgenic mice that have
      contributed to our understanding of TH function in brain development. We argue
      that astrocytes are key mediators of hormone actions on development of the
      cerebral cortex and cerebellum and that the identification of the molecules and
      pathways involved in these events might be important for determining the
      molecular-level basis of the neural deficits associated with endocrine diseases. 

PMID- 25855518
TI  - Effect of hospitalization on inappropriate prescribing in elderly Medicare
      beneficiaries.
AB  - OBJECTIVES: To determine whether acute hospitalization is associated with a
      change in potentially inappropriate medication (PIM) use and whether use varies
      across geographic region. DESIGN: Observational. SETTING: Continental United
      States. PARTICIPANTS: Medicare beneficiaries aged 65 and older hospitalized for
      acute myocardial infarction (AMI) during 2007-08. MEASUREMENTS: Potentially
      inappropriate medication use was defined according to the High-Risk Medications
      in Elderly Adults quality indicator from the Healthcare Effectiveness Data and
      Information Set. Prevalence of outpatient PIM use was determined at admission and
      discharge and then used to identify medications discontinued during
      hospitalization and incident medications started during this period. RESULTS: Of
      124,051 older adults hospitalized for AMI, 9,607 (7.7%) were outpatient PIM users
      at admission, which increased to 8.6% at discharge (P < .001). Admission PIM
      rates varied according to geographic region, as did the effect of
      hospitalization. Admission PIM use was lowest in the northeast and remained
      unchanged during hospitalization (5.1-5.1%, P = .95). In contrast, admission PIM
      use was highest in the south and increased significantly during hospitalization
      (9.9-11.4%, P < .001). PIM use also increased from the long-term perspective,
      with 6-month period prevalence rates of 22.6% before admission and 24.6% after
      discharge (P < .001). CONCLUSION: Despite intervention studies demonstrating up
      to 80% reduction in PIM use during acute hospitalization, a significant increase
      in PIM use was observed in a naturalistic setting in Medicare beneficiaries with
      AMI. Further research is needed to develop an approach to minimizing PIM use in
      the inpatient setting that is cost-effective and suitable for widespread
      implementation.

PMID- 25855520
TI  - A new possibility to assess the perioperative walking capacity using a global
      positioning system in neurosurgical spine patients: a feasibility study.
AB  - PURPOSE: It is well established that the perioperative course in terms of patient
      satisfaction, neurological function and quality of life, is assessed by
      monitoring the walking capacity. This examination method is affected by several
      primary and secondary influences. Therefore, we performed a feasibility study to
      investigate the possibility of assessing the perioperative walking capacity using
      a global positioning system (GPS) in neurosurgical spine patients. A step was
      undertaken to generate objective and reliable data for monitoring control with a
      cost-effective and easy-to-use measurement tool. METHODS: Everyday life
      activities of four patients were measured by using a GPS-capable mobile phone (a
      week preoperatively, FU 3 months later). Our custom-made software for Android
      systems continuously records the position- and movement-data of all subjects
      during the day at 1 s intervals. The position date were smoothed and checked for
      plausibility. This semi-automated process was followed by determining the total
      distance walked (TL), the average distance (AL), the average walking speed (V)
      and the total walking duration per day (T). Additionally, we are able to explore
      the measuring inaccuracy. RESULTS: In three patients, nearly all parameters were
      increased in the follow-up examination (TL: 650.76, 972.63, and 269.07%. AL:
      1213.83, 3117.89, and 72.23%. V: 78.62, -15.50, and 8.54%. T: 148.18, 4089.56,
      and 9.08%). In one patient, we documented a different motion pattern (TL: 
      54.37%, AL: -31.56%, V: -9.20%, T increased: 507.91%) due to residual limitations
      after suffering a heart attack. CONCLUSION: In this feasibility study, we
      demonstrated that this tool is able to measure the perioperative mobility and
      walking-capability. The certainty of data is dependent on the patients'
      compliance. The measuring method is used as a low cost, easily accessible, and
      easy-to-use technique, which seems to be superior to common methods like a
      treadmill-tests or walking tests. Nevertheless, these results are still to prove
      in upcoming analysis.

PMID- 25855521
TI  - EphA receptors form a complex with caspase-8 to induce apoptotic cell death.
AB  - EphA7 has been implicated in the regulation of apoptotic cell death in neural
      epithelial cells. In this report, we provide evidence that EphA7 interacts with
      caspase-8 to induce apoptotic cell signaling. First, a pull-down assay using
      biotinylated ephrinA5-Fc showed that EphA7 coprecipitated with wild type caspase
      8 or catalytically inactive caspase-8 mutant. Second, co-transfection of EphA7
      with caspase-8 significantly increased the number of cleaved caspase-3 positive
      apoptotic cells under an experimental condition where transfection of EphA7 or
      caspase-8 alone did not affect cell viability or apoptosis. EphA4 also had a
      causative role in inducing apoptotic cell death with caspase-8, whereas EphA8 did
      not. Third, caspase-8 catalytic activity was essential for the apoptotic
      signaling cascade, whereas tyrosine kinase activity of the EphA4 receptor was
      not. Interestingly, we found that kinaseinactive EphA4 was well co-localized at
      the plasma membrane with catalytically inactive caspase-8, suggesting that an
      interaction between these mutant proteins was more stable. Finally, we observed
      that the extracellular region of the EphA7 receptor was critical for interacting
      with caspase-8, whereas the cytoplasmic region of EphA7 was not. Therefore, we
      propose that Eph receptors physically associate with a transmembrane protein to
      form an apoptotic signaling complex and that this unidentified receptorlike
      protein acts as a biochemical linker between the Eph receptor and caspase-8. 

PMID- 25855522
TI  - Sulcus subarachnoid hemorrhage is a common stroke subtype in patients with
      implanted left ventricular assist devices.
AB  - BACKGROUND AND PURPOSE: Stroke is one of the major complications observed in
      patients with an implanted left ventricular assist device (LVAD). The purpose of
      this study was to clarify the types and characteristics of acute stroke in
      patients after LVAD implantation by using brain computed tomography (CT)
      findings. METHODS: Between 2005 and 2012, 110 consecutive patients who underwent
      LVAD implantation were reviewed. The most commonly used device was the pulsatile
      extracorporeal LVAD. Amongst them, 49 patients suffered from acute stroke at
      least once with a total of 115 stroke events. The clinical categories, lesion
      sites, laboratory data and CT findings of each acute stroke event were analyzed.
      RESULTS: Cerebral infarction (35 patients, 72 events), cerebral hemorrhage (25
      patients, 31 events) and subarachnoid hemorrhage (SAH) (23 patients, 33 events)
      were identified. A mean of 2.3 stroke events occurred per person. Of the 72
      infarction events, multiple infarctions were observed in 29 events. Of the
      cerebral hemorrhage events (n = 31), almost all were subcortical lesions (n = 27)
      and none were observed in the basal ganglia. Of the 23 patients with SAH events
      (n = 33), SAH localized within a single sulcus, sulcus SAH, was observed in 25
      events. CONCLUSIONS: Computed tomography findings of acute stroke after
      implantation of an LVAD are characteristically multifocal cortical lesions,
      regardless of brain infarction and hemorrhage. Unexpectedly, sulcus SAH was a
      common stroke subtype in patients with implanted LVADs. Sulcus SAH should be
      carefully examined in patients after LVAD implantation, when they complain of non
      specific neurological complaints.

PMID- 25855523
TI  - Erratum.

PMID- 25855524
TI  - Behavioral responses of the invasive Halyomorpha halys (Stal) to traps baited
      with stereoisomeric mixtures of 10,11-epoxy-1-bisabolen-3-OL.
AB  - The brown marmorated stink bug, Halyomorpha halys, is an invasive insect in the
      United States that is capable of inflicting significant yield losses for fruit,
      vegetable, and soybean growers. Recently, a male-produced aggregation pheromone
      of H. halys was identified as a 3.5:1 mixture of (3S,6S,7R,10S)-10,11-epoxy-1
      bisabolen-3-ol and (3R,6S,7R,10S)-10,11-epoxy-1-bisabolen-3-ol, two stereoisomers
      of a natural sesquiterpene with a bisabolane skeleton, potentially existing in 16
      stereoisomeric forms. In this study, we assessed attraction to pheromonal and non
      pheromonal stereoisomeric mixtures of 10,11-epoxy-1-bisabolen-3-ol, which are
      easier to synthesize than single isomers, and evaluated dose-dependent responses
      to attractive mixtures in field trials. Some treatments not containing the
      natural pheromone components were moderately active in field-trapping studies,
      signifying that some stereoisomers of 10,11-epoxy-1-bisabolen-3-ol are
      sufficiently similar to the true pheromone in structure to trigger behavioral
      responses. Importantly, we found that mixtures of stereoisomers containing
      pheromone components were also highly attractive to H. halys, even in the
      presence of multiple "unnatural" stereoisomers. Further, adult and nymphal
      captures were dose-dependent, regardless of whether the lure contained pheromonal
      or non-pheromonal components. Our findings of attraction to pheromonal and non
      pheromonal stereoisomers and lack of inhibition from non-pheromonal stereoisomers
      of 10,11-epoxy-1-bisabolen-3-ol increase the flexibility of developing pheromone
      based products for H. halys. 

PMID- 25855525
TI  - Organic carbon removal from wastewater by a PHA storing biofilm using direct
      atmospheric air contact as oxygen supply.
AB  - The principal reason for the high energy costs for biological wastewater
      treatment is the poor transfer efficiency of oxygen to the bulk water phase. The
      current paper describes a biofilm reactor in which oxygen transfer to the bulk
      solution is avoided by alternating anaerobic submersed (2h) and drained (1h)
      operation of the biofilm. During the submersed phase the biofilm enriched for
      glycogen accumulating organism (GAO) stored the organic carbon (acetate) as poly
      hydroxy-alkanoate (PHA). After draining the reactor, this carbon stored as PHA
      was biologically oxidised, using oxygen directly from the atmosphere. The
      12Cmmol/L (384mg/L BOD) of acetate was completely removed during long term
      automated operation of the reactor for 9months with a cycle length of 3.3h. As
      the process specifically removes dissolved organic carbon but not N or P it could
      possibly be coupled with novel processes such as Anammox or nutrient recovery. 

PMID- 25855526
TI  - Evaluation of ultrasonic, acid, thermo-alkaline and enzymatic pre-treatments on
      anaerobic digestion of Ulva rigida for biogas production.
AB  - Pre-treatment of macroalgae has received considerable research globally due to
      its influence on the technical, economic and environmental sustainability of
      algae biogas production. Some of the most promising pre-treatment methods require
      the application of chemicals, enzymatic, and mechanical. This study focused on
      these pre-treatments of Ulva rigida for biogas production. The evaluation of
      different pre-treatment in terms of reducing sugar yields demonstrates that 3.62,
      2.88, 2.53 and 7.3g/L of reducing sugar was obtained in acid catalysis,
      thermoalkaline, ultrasonication and enzymatic pre-treatment, respectively.
      However in crude macroalgae only 0.6g/L of reducing sugar was given. After
      anaerobic digestion, the enzymatic hydrolysis was demonstrated the best biogas
      yield than other pre-treatment which reached 626.5mL/gCODint with 62.65% of
      biodegradability. The best demonstrated method which uses crude broth of
      Aspergillus niger showed an effective and environmentally friendly strategy for
      enhancing the biogas production yields after the anaerobic digestion. 

PMID- 25855527
TI  - Effect of TiO2 nanoparticles on aerobic granulation of algal-bacterial symbiosis
      system and nutrients removal from synthetic wastewater.
AB  - The influence of TiO2 nanoparticles (TiO2-NPs) (10-50mg/L) on aerobic granulation
      of algal-bacterial symbiosis system was investigated by using two identical
      sequencing batch reactors (SBRs). Although little adverse effect was observed on
      their nitritation efficiency (98-100% in both reactors), algal-bacterial granules
      in the control SBR (Rc) gradually lost stability mainly brought about by algae
      growth. TiO2-NPs addition to RT was found to enhance the granulation process
      achieving stable and compact algal-bacterial granules with remarkably improved
      nitratation thus little nitrite accumulation in RT when influent TiO2-NPs?30mg/L.
      Despite almost similar organics and phosphorus removals obtained in both
      reactors, the stably high nitratation efficiency in addition to much stable
      granular structure in RT suggests that TiO2-NPs addition might be a promising
      remedy for the long-term operation of algal-bacterial granular system, most
      probably attributable to the stimulated excretion of extracellular polymeric
      substances and less filamentous TM7. 

PMID- 25855529
TI  - Case of pseudolymphoma with bald patches on the scalp.

PMID- 25855528
TI  - Incorporation of Decomposed Crop Straw Affects Potential Phytoavailability of
      Mercury in a Mining-Contaminated Farming Soil.
AB  - Recently, incorporation of crop straw into soils is being largely encouraged
      worldwide. To explore the possible influence of incorporation of decomposed crop
      straw on the speciation (i.e., inorganic mercury/IHg, and methylmercury/MMHg) and
      phytoavailability of mercury, mercury-contaminated farming soil was amended with
      different amounts (i.e., low, medium or high) of straw organic fertilizer (SF,
      mainly consisting of decomposed rice straw) or humus (HU) and incubated for a
      month. Potential phytoavailability of IHg, assessed by CaCl2 extraction, was
      significantly lower in soils amended with low/medium SF, possibly due to the
      immobilization effect of SF-organic matter on IHg. In contrast, phytoavailability
      of IHg was significantly higher in soils incorporated with high HU, possibly
      explained by the leaching effect of dissolved HU on soil-bound IHg. For MMHg,
      incorporation of medium/high HU significantly increased MMHg phytoavailability,
      while SF addition had little effect. Interestingly, MMHg levels in SF/HU amended
      soils were generally lower than that in soil receiving no amendment, probably
      because complexation of IHg with SF/HU organics decreased IHg availability to
      methylation microorganisms. Overall, current results suggested that incorporation
      of decomposed crop straw may have multiple effects on mercury biogeochemistry in
      soils, which should be considered when applying SF into mercury-contaminated
      farming soils. 

PMID- 25855530
TI  - Endothelin receptor B protects granulocyte macrophage colony-stimulating factor
      mRNA from degradation.
AB  - Evidence is lacking on the differential effects of the two therapeutic concepts
      of endothelin receptor antagonists (ERAs): the blockade of only the endothelin
      receptor A (ETAR; selective antagonism) versus both ETAR and endothelin receptor
      B (ETBR; dual blockade). Ambrisentan, a selective ERA, and bosentan, a dual
      blocker, are both available for therapy. We hypothesized that there are
      differences in the potential of ERAs to ameliorate inflammatory processes in
      human airway smooth muscle cells (HASMCs) and aimed to unravel underlying
      mechanisms. We used HASMC culture, enzyme-linked immunosorbent assay, and
      quantitative reverse-transcription polymerase chain reaction. Tumor necrosis
      factor alpha (TNFalpha) induced transcription and expression of chemokine (C-X-C
      motif) ligand 2 (CXCL2), chemokine (C-X-C motif) ligand 3 (CXCL3), granulocyte
      macrophage colony-stimulating factor (GM-CSF), and matrix metalloproteinase 12
      (MMP12) in HASMCs. In concentration-response experiments, bosentan led to a
      significantly greater reduction of GM-CSF and MMP12 protein release than
      ambrisentan, whereas there was no significant difference in their effect on GM
      CSF and MMP12 mRNA. Both ERAs reduced CXCL3 protein and mRNA equally but had no
      effect on CXCL2. Blocking mitogen-activated protein kinases revealed that both
      ETAR and ETBR signal through p38 mitogen-activated protein kinase, but ETBR also
      signals through extracellular signal-regulated kinase (ERK) 1/2 to induce GM-CSF
      expression. In the presence of the transcription inhibitor actinomycin D,
      bosentan, but not ambrisentan, reduced GM-CSF but not MMP12 or CXCL3 mRNA. In
      conclusion, blockade of each endothelin receptor subtype reduces GM-CSF
      transcription, but blocking ETBR additionally protects GM-CSF mRNA from
      degradation via ERK-1/2. Accordingly, blocking both ETAR and ETBR leads to a
      stronger reduction of TNFalpha-induced GM-CSF protein expression. This mechanism
      might be specific to GM-CSF. Our data stress the anti-inflammatory potential of
      ERA and warrant further investigation of their utility in chronic inflammatory
      airway diseases. 

PMID- 25855531
TI  - The outcomes and treatment burden of childhood acute myeloid leukaemia in
      Australia, 1997-2008: A report from the Australian Paediatric Cancer Registry.
AB  - Childhood acute myeloid leukaemia (AML) requires intensive therapy and is
      associated with survival rates that are substantially inferior to many other
      childhood malignancies. We undertook a retrospective analysis of Australian
      Paediatric Cancer Registry data from 1997 to 2008 together with a single-centre
      audit during the same period assessing burden on service delivery at a tertiary
      children's hospital (Royal Children's Hospital, Brisbane). Although survival
      improved from 54.3% (1997-2002) to 69.2% (2003-2008), childhood AML caused a
      disproportionate number of childhood cancer deaths, accounting for 5.5% of all
      childhood cancer diagnoses yet 7.9% of all childhood cancer mortality.
      Furthermore, treatment was associated with significant toxicity requiring
      intensive use of local health resources. Novel therapeutic strategies aimed at
      improving survival and reducing toxicity are urgently required.

PMID- 25855532
TI  - Nickel-catalyzed directed sulfenylation of sp(2) and sp(3) C-H bonds.
AB  - Directed sulfenylation of both sp(2) and sp(3) C-H bonds was achieved through
      nickel catalyzed directed C-S bond formation, giving the desired product in good
      to excellent yield (up to 90%). Other metal cations, including Cu, Fe, Pd, Rh, Ru
      and Co, gave almost no reaction under identical conditions, which highlighted the
      unique reactivity of this Ni system. 

PMID- 25855533
TI  - Thermally-induced chemical-order transitions in medium-large alloy nanoparticles
      predicted using a coarse-grained layer model.
AB  - A new coarse-grained layer model (CGLM) for efficient computation of axially
      symmetric elemental equilibrium configurations in alloy nanoparticles (NPs) is
      introduced and applied to chemical-order transitions in Pt-Ir truncated octahedra
      (TOs) comprising up to tens of thousands of atoms. The model is based on
      adaptation of the free energy concentration expansion method (FCEM) using
      coordination-dependent bond-energy variations (CBEV) as input extracted from DFT
      computed elemental bulk and surface energies. Thermally induced quite sharp
      transitions from low-T asymmetric quasi-Janus and quasi ball-and-cup
      configurations to symmetric multi-shells furnish unparalleled nanophase composite
      diagrams for 1289-, 2406- and 4033-atom NPs. At even higher temperatures entropic
      atomic mixing in the multi-shells gradually intensifies, as reflected in broad
      heat-capacity Schottky humps, which become sharper for much larger TOs (e.g., ~10
      nm, ~30,000 atoms), due to transformation to solid-solution-like cores.

PMID- 25855534
TI  - Necker's smile: Immediate affective consequences of early perceptual processes.
AB  - Current theories assume that perception and affect are separate realms of the
      mind. In contrast, we argue that affect is a genuine online-component of
      perception instantaneously mirroring the success of different perceptual stages.
      Consequently, we predicted that the success (failure) of even very early and
      cognitively encapsulated basic visual processing steps would trigger immediate
      positive (negative) affective responses. To test this assumption, simple visual
      stimuli that either allowed or obstructed early visual processing stages without
      participants being aware of this were presented briefly. Across 5 experiments, we
      found more positive affective responses to stimuli that allowed rather than
      obstructed Gestalt completion at certain early visual stages (Experiments 1-3;
      briefest presentation 100 ms with post-mask), and visual disambiguation in
      possible vs. impossible Necker cubes (Experiments 4 and 5; briefest presentation
      100 ms with post-mask). This effect was observed both on verbal preference
      ratings (Experiments 1, 2, and 4) and as facial muscle responses occurring within
      2-4 s after stimulus onset (zygomaticus activity; Experiments 3 and 7). For
      instance, in participants unaware of spatial possibility we found affective
      discrimination between possible and impossible Necker cubes (the famous Freemish
      Crate) for 100 ms presentation timings, although a conscious discrimination took
      more than 2000 ms (Experiment 4).

PMID- 25855535
TI  - Analysis of false-positive results of fetal RHD typing in a national screening
      program reveals vanishing twins as potential cause for discrepancy.
AB  - OBJECTIVES: We aim to elucidate causes of false-positive fetal RHD screening
      results obtained with cell-free DNA. METHODS: Fetal RHD screening was performed
      in 32,222 samples from RhD-negative women by multiplex real-time PCR in
      triplicate for RHD exons 5 and 7 using cell-free DNA isolated from maternal
      plasma obtained in the 27th gestational week. PCR results were compared with cord
      blood serology in 25,789 pregnancies (80.04%). False-positive cases were
      analyzed. Known biological causes (RHD variant genes), technical causes of
      discordance, and errors around blood sampling were investigated with leukocyte
      DNA from maternal and cord blood, and cell-free DNA from stored maternal plasma.
      RESULTS: Not only RHD but also Y-chromosome (DYS14) sequences were present in
      four plasma samples from RHD-negative women bearing an RHD-negative girl. Sample
      mix-up and other sampling errors could be excluded in three samples. CONCLUSIONS:
      These results indicate that false-positive fetal RHD screening results can be
      caused by cell-free DNA fragments in maternal plasma derived from a third cell
      line that is not representative for either the maternal genome or the genome of
      the vital fetus. We propose that remaining (cyto)trophoblasts of a vanishing twin
      are the underlying mechanism, and we estimate a frequency of this phenomenon of
      0.6%.

PMID- 25855538
TI  - [Migrants: a few hospitalisations, too many deaths in the Mediterranean Sea].

PMID- 25855536
TI  - Whole-exome sequencing of pancreatic cancer defines genetic diversity and
      therapeutic targets.
AB  - Pancreatic ductal adenocarcinoma (PDA) has a dismal prognosis and insights into
      both disease etiology and targeted intervention are needed. A total of 109 micro
      dissected PDA cases were subjected to whole-exome sequencing. Microdissection
      enriches tumour cellularity and enhances mutation calling. Here we show that
      environmental stress and alterations in DNA repair genes associate with distinct
      mutation spectra. Copy number alterations target multiple tumour
      suppressive/oncogenic loci; however, amplification of MYC is uniquely associated
      with poor outcome and adenosquamous subtype. We identify multiple novel mutated
      genes in PDA, with select genes harbouring prognostic significance. RBM10
      mutations associate with longer survival in spite of histological features of
      aggressive disease. KRAS mutations are observed in >90% of cases, but codon Q61
      alleles are selectively associated with improved survival. Oncogenic BRAF
      mutations are mutually exclusive with KRAS and define sensitivity to vemurafenib
      in PDA models. High-frequency alterations in Wnt signalling, chromatin
      remodelling, Hedgehog signalling, DNA repair and cell cycle processes are
      observed. Together, these data delineate new genetic diversity of PDA and provide
      insights into prognostic determinants and therapeutic targets. 

PMID- 25855537
TI  - MORF-RELATED GENE702, a Reader Protein of Trimethylated Histone H3 Lysine 4 and
      Histone H3 Lysine 36, Is Involved in Brassinosteroid-Regulated Growth and
      Flowering Time Control in Rice.
AB  - The methylation of histone H3 lysine 36 (H3K36) plays critical roles in
      brassinosteroid (BR)-related processes and is involved in controlling flowering
      time in rice (Oryza sativa). Although enzymes that catalyze this methylation
      reaction have been described, little is known about the recognition mechanisms to
      decipher H3K36 methylation information in rice. In this study, biochemical
      characterizations showed that MORF-RELATED GENE702 (MRG702) binds to
      trimethylated H3K4 and H3K36 (H3K4me3 and H3K36me3) in vitro. Similar to the loss
      of-function mutants of the rice H3K36 methyltransferase gene SET DOMAIN GROUP725
      (SDG725), the MRG702 knockdown mutants displayed typical BR-deficient mutant and
      late-flowering phenotypes. Gene transcription analyses showed that MRG702
      knockdown resulted in the down-regulation of BR-related genes, including DWARF11,
      BRASSINOSTEROD INSENSITIVE1, and BRASSINOSTEROID UPREGULATED1, and several
      flowering genes, including Early heading date1 (Ehd1), Ehd2, Ehd3, OsMADS50,
      Heading date 3a, and RICE FLOWERING LOCUS T1. A binding analysis showed that
      MRG702 directly binds to the chromatin at target gene loci. This binding is
      dependent on the level of trimethylated H3K36, which is mediated by SDG725.
      Together, our results demonstrate that MRG702 acts as a reader protein of H3K4me3
      and H3K36me3 and deciphers the H3K36 methylation information set by SDG725.
      Therefore, the role of MRG702 in the BR pathway and in controlling flowering time
      in rice is to function as a reader protein to decipher methylation information. 

PMID- 25855539
TI  - [Vaccines, what a mess!].

PMID- 25855540
TI  - [Epidemiologia e Prevenzione, a tool for the Italian Public HealthManifesto for a
      tobacco endgame strategy in Italy].

PMID- 25855541
TI  - [Tobacco control experience in the debate on marijuana legalisation].

PMID- 25855542
TI  - [The NINFEA project and the emerging forms of engagement of citizens in
      epidemiological research].
AB  - In the last decade a new form of participation of the citizens in research
      activities and in the production of knowledge has emerged.This development has
      started to reach epidemiological research, as illustrated in the recent section
      "EpiChange" of the journal Epidemiologia e Prevenzione. The conduction of
      epidemiological research through the engagement of citizens and new forms of
      production of knowledge - including peer-production - is still in its infancy. In
      2005,we started in Italy a birth cohort, the NINFEA project, which uses the
      Internet to recruit pregnant women and to follow-up their children. Participants
      are volunteers who decide to take part in the research project. In this paper, we
      consider the aspects of the NINFEA project that are consistent with the concept
      of collaborative production of knowledge. In particular,we discuss issues related
      to the motivation of the participants, the selection of the research hypotheses
      to be evaluated and the definition of the population of interest of the study. 

PMID- 25855543
TI  - [Impact of a Decree on ACE inhibitors/ARBs in cardiovascular secondary prevention
      in the Lazio Region (Central Italy): a pre-post analysis].
AB  - OBJECTIVES: to evaluate the effect of the 2010 legal decree (DCA) in the Lazio
      Region (Central Italy), promoting appropriateness on use of agents acting on the
      renin-angiotensin system, and limiting use of angiotensin II receptor blockers
      (ARBs) within this drug group to levels below 30%. SETTING AND PARTICIPANTS: two
      cohorts of incident patients with diagnosis of cardiovascular disease (CVD) were
      enrolled from the regional hospital information system: the first cohort included
      patients discharged during the 12 months before DCA (35,917 patients), and the
      second one patients discharged during the 12 months after DCA (35,491 patients).
      DESIGN: the first prescriptions of angiotensin- converting enzyme inhibitors
      (ACEIs) and ARBs in the 30 days after discharge were collected from the drug
      claims registry. The trends of monthly prescription proportions for the two drug
      groups were compared through a segmented regression analysis. MAIN OUTCOMES
      MEASURES: comparison between the pre- and post-DCA periods, distinguishing
      between prescription made by hospital physicians and by general practitioners,
      and between naive and prevalent users. RESULTS: proportion of patients with CVD
      treated with ACEIs/ARBs after discharge was 50% in both pre-DCA (35,917 patients)
      and post-DCA (35,491 patients) cohorts, with the same share of ACEIs (60%) and
      ARBs (40%). ARB proportions met the threshold only for hospital prescriptions.
      Among naive users, the target was met for both hospital physicians and general
      practitioners. CONCLUSIONS: the specific DCA has not led to an overall
      improvement in the appropriateness of prescribing of ACEIs/ARBs in secondary
      cardiovascular prevention. However, there is a suitable prescription choice for
      naive patients and when the drug is dispensed in hospital pharmacies.

PMID- 25855545
TI  - [Prevalence, mortality and lethality of congenital heart defects from the Tuscan
      Registry (Tuscany Region, Central Italy), 1992-2009].
AB  - OBJECTIVES: to estimate prevalence, mortality and lethality of congenital heart
      defects (CHDs), and to evaluate time trend by comparing two birth cohorts (1992-
      2000 vs. 2001-2009). DESIGN: descriptive study using a population-based registry:
      the Tuscan Registry of congenital defects (RTDC), which is a member of the
      European network of surveillance of congenital anomalies (EUROCAT) since 1979.
      SETTING AND PARTICIPANTS: CHD cases were collected by the RTDC between 1992 and
      2009. MAIN OUTCOME MEASURES: prevalence and mortality rates were calculated for
      all and non-chromosomal CHDs. The non-chromosomal cases were classified in three
      severity classes (SI, SII, SIII), according to decreasing perinatal mortality. It
      was estimated prevalence of: live births, foetal deaths (stillbirths and
      spontaneous abortions from 20 weeks gestation), terminations of pregnancy for
      foetal anomaly (TOPFAs) at any gestational age, and of prenatally diagnosed
      cases. Perinatal, neonatal and infant mortality were calculated. Early-neonatal,
      neonatal and infant lethality were calculated for the non-chromosomal cases.
      RESULTS: 3,653 cases were identified out of 486,947 live births and 1,883
      stillbirths, 95% of which were non-chromosomal cases. The total average
      prevalence was 7.47/1,000 births. The overall prevalence decreased significantly
      in all CHDs (Prevalence ratio - PR: 0.86; 95%CI 0.80-0.91) as well as in non
      chromosomal (PR: 0.86; 95%CI 0.80-0.92), while in the more severe defects (SI/SII
      combined cases) the total prevalence was stable over time. In more severe cases,
      prevalence of live births decreased significantly (PR: 0.83; 95%CI 0.71-0.97),
      while the greater increase of TOPFAs and of diagnosed cases was observed in the
      prenatal period. All three mortality rates reduced significantly over time. In
      the more severe cases, the greatest rate mortality reduction was observed for
      neonatal mortality (Mortality ratio - MR: 0.29; 95%CI 0.16-0.49) than perinatal
      (MR: 0.37; 95%CI 0.19-0.70) and infant mortality (MR: 0,40; 95%CI 0.28-0.56). In
      this group of CHDs, early neonatal lethality decreased from 10% to 3%, neonatal
      lethality from 17% to 6%, and infant lethality from 24% to 10%. CONCLUSIONS: the
      results suggest that the improvements in prenatal diagnosis and in foetal and
      neonatal treatment and care have reduced the burden of congenital heart defects
      on the health of the Tuscany population.

PMID- 25855544
TI  - [Pollutants from a plant which burns toxic waste in the Province of Arezzo
      (Tuscany Region, Central Italy): human biomonitoring pilot study to evaluate the
      possible type of environmental exposure].
AB  - OBJECTIVES: to identify the biomarkers to use in order to evaluate the level and
      trend of exposure to environmental pollutants from a plant which retrieves and
      refines precious metals and burns toxic waste. DESIGN: human biomonitoring cross
      sectional study on a small sample of population resident in the study area.
      SETTING AND PARTICIPANTS: blood and urinary samples, and questionnaires from
      volunteers resident at least for 10 years in Civitella in Val di Chiana area
      (Arezzo Province, Tuscany Region, Central Italy), where the plant is located, and
      in a control area; they had to be 5-year non-smokers or ex-smokers, in good
      health status and non occupationally exposed to heavy metals and/or combustion
      products. MAIN OUTCOME MEASURES: geometric mean and 95th percentile (P95) of
      mercury (Hg) and cadmium (Cd) blood concentrations, and of the urinary
      concentrations of antimony (Sb), silver (Ag), arsenic (As), Cd, cobalt (Co),
      chromium (Cr), Hg, nickel (Ni), platinum (Pt), 1-hydroxypyrene, and trans, trans
      muconic acid in the two populations; quantity and pattern of porphyrins in the 24
      hour urines of Civitella volunteers. Student's "t" test calculated on the means
      of data with logarithmic transformation was used to compare the two groups. In
      case of significant differences linear regression analyses have been performed
      using questionnaire information. The distribution of observed data was compared
      with specific reference values. RESULTS: Sb, Cd, and Ni concentrations were
      significantly higher in Civitella population (39 subjects), while Cr
      concentration was higher in the control group (18 subjects). No correlations with
      the individual characteristics have been observed. The 30.3%of subjects who gave
      their 24- hour urine had a distorted pattern of porphyrins. CONCLUSION: the
      results confirmed the need to perform human biomonitoring in the Civitella area,
      increasing the number of samples, using urine as biological matrix, and
      monitoring at least Sb, Cd, Ni, Pt, Ag, and porphyrins.

PMID- 25855546
TI  - [Epidemiological study of dental and facial asymmetries in a sample of preschool
      subjects].
AB  - OBJECTIVES: to identify the typologies of facial and dental asymmetries in a
      sample of children aged between 3 and 6 years and to correlate these asymmetries
      with possible morphological and functional situations. DESIGN: cross-sectional
      observational study. SETTING AND PARTICIPANTS: sample of 95 subjects aged between
      3 and 6 years. Clinical data were collected in 10 sessions conducted during
      school hours in April 2013 by a doctor of Dentistry at two preschools in the city
      of Sanremo (Liguria Region, Northern Italy) and a kindergarten in the city of
      Pavia (Lombardy Region, Northern Italy). To collect the data, a weighted clinical
      questionnaire was used. MAIN OUTCOME MEASURES: presence and type of bad habit,
      type of breathing, presence and type of facial asymmetry, dental formula,
      presence of diastema, presence and type of occlusal asymmetries, presence and
      type of dental malocclusions. RESULTS: analysed sample consisted of 53.7% (51/95)
      of males and 46.3 % (44/95) females; the mean age was 4.3 +/- 0.9 years. Most
      frequent facial asymmetry is orbits asymmetry (35%, 33/95); dental malocclusions
      are detected in 70%(67/95) of cases. High percentage of subjects (69.5%, 66/95)
      presents displacement between superior dental midline (SDM) and inferior dental
      midline (IDM). Several statistically significant associations are observed: in
      particular, asymmetry of molar ratios is linked to asymmetry of the cheekbones
      and displacement of the SDM; facial midline has statistical association with
      asymmetry of the cheekbones (p <0.001). CONCLUSIONS: the results of this study
      agree with scientific literature, in particular as regards the prevalence of
      compromising habits observed and the close correlation between: the presence of
      dental malocclusions and the presence of compromising habits, the presence of
      dental malocclusions and the presence of oral breathing.

PMID- 25855547
TI  - [Inverse probability weighting (IPW) and baseline selection in etiological cohort
      studies].

PMID- 25855549
TI  - [A Parliament debate regarding a scientific study].
AB  - Publishing studies on the relationship between health and pollution provokes
      reactions and interest in the public opinion involved, the highest national
      institutions included. This commentary, aroused by a parliamentary debate, which
      also concerned one of our recent scientific papers published on Environmental
      Research about the association between congenital anomalies and maternal exposure
      to atmospheric pollutants in Brindisi (Apulia Region, Southern Italy), aims at
      contributing to reply the following questions: the type and quality of the data
      used in the estimates of exposure must be certified by institutional bodies?
      Adverse health effects in people exposed to pollutants at levels below the law
      limits can be excluded? Finally, we draw some remarks on measures to protect
      public health and on the relationship between the work of the researchers of
      public institutes and administrations.

PMID- 25855548
TI  - [Causes of hospitalisation of migrants arrived in Lampedusa (Southern Italy) from
      January 2011 to June 2014].
AB  - This is the synthesis of a study on admissions of migrants to hospitals in
      Sicily, from January 2011 to June 2014. Migrants arrived in Lampedusa were 49,000
      in 2011; 4,000 in 2012; 15,000 in 2013; 6,000 in 2014; 378 patients requiring
      hospitalization were transported exclusively by the 118 Helicopter Emergency
      Medical Service in 6 Sicilian hospitals: 203 in 2011, 62 in 2012, 95 in 2013, 18
      in 2014. The mean age was 25 years; more frequent areas of provenance were Horn
      of Africa, North Africa, Syria, and Nigeria. Women were hospitalised almost
      exclusively for obstetric-gynaecological problems, with a high prevalence of
      abortions (17/140 pregnancies) secondary to the long journey; men were
      hospitalised especially for bone fractures, burns, dehydration, infectious
      diseases, suicide attempts, and, recently, for CO poisoning of people locked in
      the holds of boats. Infectious diseases were mainly due to respiratory and
      intestinal distress, 20 people had tuberculosis (TB), 3 had HIV and 1 had
      malaria. No suspicious of Ebola virus infection was registered. The causes of
      hospitalisation do not depend on the nationality of patients and are constant
      over the years. Infectious diffusible diseases, mainly TB, are more common than
      in the Italian population, and consequently the best surveillance systems, aimed
      at identifying and treating patients immediately, should be activated. Mare
      Nostrum Operation helped migrants while they are in sea and allowed the reduction
      of serious health problems, mainly related to the hardships and duration of the
      journey, and also anticipating arrivals directly in Lampedusa, permitting a more
      efficient organisation of the relief in the sea. 

PMID- 25855550
TI  - [Italy 2014: 1,000 new cancer cases every day, but mortality is decreasing].

PMID- 25855551
TI  - [Italy 2014: childhood obesity is decreasing].

PMID- 25855552
TI  - [Sociodemographic variation in childhood overweight and obesity in Italy in
      2014].

PMID- 25855553
TI  - [Manual workers are more likely to adopt unhealthy habits].

PMID- 25855554
TI  - Comparison of Two Commercial Type 1 Porcine Reproductive and Respiratory Syndrome
      Virus (PRRSV) Modified Live Vaccines against Heterologous Type 1 and Type 2 PRRSV
      Challenge in Growing Pigs.
AB  - The objective of the present study was to compare the efficacy of two commercial
      type 1 porcine reproductive and respiratory syndrome virus (PRRSV) modified live
      vaccines against heterologous type 1 and type 2 PRRSV challenge in growing pigs.
      Vaccination with a type 1 PRRSV vaccine reduced the level of viremia after type 1
      PRRSV challenge but did not reduce the level of viremia after the type 2 PRRSV
      challenge in pigs. Increased levels of interleukin-10 (IL-10) stimulated by type
      2 PRRSV coincided with the low numbers of type 2 PRRSV-specific interferon gamma
      secreting cells (IFN-gamma-SC) in vaccinated pigs after type 2 PRRSV challenge,
      whereas low levels of IL-10 stimulated by type 1 PRRSV coincided with high
      numbers of type 1 PRRSV-specific IFN-gamma-SC in vaccinated pigs after type 1
      PRRSV challenge. Additionally, vaccination with the type 1 PRRSV vaccine
      effectively reduced the lung lesions and type 1 PRRSV nucleic acids in type 1
      PRRSV-challenged pigs but did not reduce lung lesions and type 2 PRRSV nucleic
      acids in type 2 PRRSV-challenged pigs. There were no significant differences
      between two commercial type 1 PRRSV vaccines against type 1 and type 2 PRRSV
      challenge based on virological results, immunological responses, and pathological
      outcomes. This study demonstrates that vaccinating pigs with the type 1 PRRSV
      vaccine provides partial protection against respiratory disease with heterologous
      type 1 PRRSV challenge but no protection with heterologous type 2 PRRSV
      challenge. 

PMID- 25855556
TI  - Tackling High Blood Pressure in England: A New Approach.

PMID- 25855555
TI  - Effects of Serial Skin Testing with Purified Protein Derivative on the Level and
      Quality of Antibodies to Complex and Defined Antigens in Mycobacterium bovis
      Infected Cattle.
AB  - Several serological tests designed to detect antibodies to immunodominant
      Mycobacterium bovis antigens have recently emerged as ancillary tests for the
      detection of bovine tuberculosis in cattle, particularly when used after the
      injection of purified protein derivative (PPD) for skin testing, which
      significantly boosts M. bovis-specific antibody responses. The present findings
      demonstrate the onset and duration of boosted antibody responses after the
      injection of M. bovis PPD for the caudal fold test (CFT) and Mycobacterium avium
      and M. bovis PPDs for the comparative cervical test (CCT), administered in series
      in cattle experimentally infected with M. bovis. While skin tests boosted the
      responses to certain antigens (i.e., MPB83 and MPB70), they did not affect the
      responses to other antigens (e.g., ESAT-6, CFP10, MPB59, and MPB64).
      Administration of the CCT 105 days after the CFT resulted in an even greater
      secondary boost in antibody responses to MPB83 and MPB70 and to a proteinase K
      digested whole-cell sonicate (WCS-PK) of M. bovis. Both IgM and IgG contributed
      to the initial boost in the MPB83/MPB70-specific antibody response after the CFT.
      The secondary boost after the CCT was primarily due to increased IgG levels.
      Also, the avidity of antibodies to MPB83 and MPB70 increased after the CCT in M.
      bovis-infected cattle. The avidity of antibodies to the WCS-PK antigens increased
      in the interval between the CFT and the CCT but did not increase further after
      the CCT. Together, these findings demonstrate that the administration of PPDs for
      skin tests results in additive enhancement (i.e., when the CFT and CCT are
      performed in series), both qualitative and quantitative, of MPB83/MPB70-specific
      antibody responses. 

PMID- 25855557
TI  - The importance of negative defensive medicine in the effects of malpractice
      reform.
AB  - This article presents a model of physician and insurer behavior in which the
      practice of defensive medicine, both positive and negative, can arise. Accounting
      for negative defensive medicine, and insurers' reaction to it, leads to different
      predictions of the effects of changing malpractice pressure compared to past
      models. Rising malpractice pressure causes both health care spending and quality
      to increase up to a threshold, and decrease thereafter. This non-monotonicity
      implies that malpractice reform is not a "silver bullet" capable of achieving
      both cost reductions and quality improvements for all consumers. The results can
      further explain inconsistent findings in the empirical literature and suggest
      alternative specifications for estimating the effects of malpractice reform. 

PMID- 25855558
TI  - The mediating effect of gaming motivation between psychiatric symptoms and
      problematic online gaming: an online survey.
AB  - BACKGROUND: The rapid expansion of online video gaming as a leisure time activity
      has led to the appearance of problematic online gaming (POG). According to the
      literature, POG is associated with different psychiatric symptoms (eg,
      depression, anxiety) and with specific gaming motives (ie, escape, achievement).
      Based on studies of alcohol use that suggest a mediator role of drinking motives
      between distal influences (eg, trauma symptoms) and drinking problems, this study
      examined the assumption that there is an indirect link between psychiatric
      distress and POG via the mediation of gaming motives. Furthermore, it was also
      assumed that there was a moderator effect of gender and game type preference
      based on the important role gender plays in POG and the structural differences
      between different game types. OBJECTIVE: This study had two aims. The first aim
      was to test the mediating role of online gaming motives between psychiatric
      symptoms and problematic use of online games. The second aim was to test the
      moderator effect of gender and game type preference in this mediation model.
      METHODS: An online survey was conducted on a sample of online gamers (N=3186;
      age: mean 21.1, SD 5.9 years; male: 2859/3186, 89.74%). The Brief Symptom
      Inventory (BSI), the Motives for Online Gaming Questionnaire (MOGQ), and the
      Problematic Online Gaming Questionnaire (POGQ) were administered to assess
      general psychiatric distress, online gaming motives, and problematic online game
      use, respectively. Structural regression analyses within structural equation
      modeling were used to test the proposed mediation models and multigroup analyses
      were used to test gender and game type differences to determine possible
      moderating effects. RESULTS: The mediation models fitted the data adequately. The
      Global Severity Index (GSI) of the BSI indicated that the level of psychiatric
      distress had a significant positive direct effect (standardized effect=.35,
      P<.001) and a significant indirect (mediating) effect on POG (standardized
      effect=.194, P<.001) via 2 gaming motives: escape (standardized effect=.139,
      P<.001) and competition (standardized effect=.046, P<.001). The comparison of the
      2 main gamer types showed no significant differences in the model. However, when
      comparing male and female players it was found that women had (1) slightly higher
      escape scores (on a 5-point Likert scale: mean 2.28, SD 1.14) than men (mean
      1.87, SD 0.97) and (2) a stronger association between the escape motive and
      problematic online gaming (standardized effect size=.64, P<.001) than men
      (standardized effect size=.20, P=.001). CONCLUSIONS: The results suggest that
      psychiatric distress is both directly and indirectly (via escape and competition
      motives) negatively associated with POG. Therefore, the exploration of
      psychiatric symptoms and gaming motives of POG can be helpful in the preparation
      of prevention and treatment programs.

PMID- 25855559
TI  - Pooled genetic analysis reveals an association of SNPs of only a few genes with
      risk predisposition to ischemic stroke in a Chinese population.
AB  - Up to date, series of studies on ischemic stroke had resulted in inconsistent
      conclusion. In this study, we aimed to evaluate which specific genes were
      associated with increased predisposition to stroke in a Chinese population. To
      identify the specific genes and polymorphisms associated with predisposition to
      ischemic stroke, we performed high throughput sequenom based next-generation
      sequencing from 743 patient with history of ischemic stroke. Variants SNPs in
      nNOS, renalase, MTHFR, CELSR1 and XYLB genes were found significantly associated
      with IS, thus suggesting involvement of these loci to IS in Chinese patients.
      Because of different locations on chromosomes, haplotype analyses were not
      feasible. Our results demonstrate the top level genes that are related to normal
      vascular physiology, viz. genes of nitric oxide synthesis, endothelial health and
      smooth muscle biology. Further validation studies are awaited.

PMID- 25855560
TI  - Comprehensive multiphase NMR: a promising technology to study plants in their
      native state.
AB  - Nuclear magnetic resonance (NMR) spectroscopy is arguably one the most powerful
      tools to study the interactions and molecular structure within plants.
      Traditionally, however, NMR has developed as two separate fields, one dealing
      with liquids and the other dealing with solids. Plants in their native state
      contain components that are soluble, swollen, and true solids. Here, a new form
      of NMR spectroscopy, developed in 2012, termed comprehensive multiphase (CMP)-NMR
      is applied for plant analysis. The technology composes all aspects of solution,
      gel, and solid-state NMR into a single NMR probe such that all components in all
      phases in native unaltered samples can be studied and differentiated in situ. The
      technology is evaluated using wild-type Arabidopsis thaliana and the cellulose
      deficient mutant ectopic lignification1 (eli1) as examples. Using CMP-NMR to
      study intact samples eliminated the bias introduced by extraction methods and
      enabled the acquisition of a more complete structural and metabolic profile;
      thus, CMP-NMR revealed molecular differences between wild type (WT) and eli1 that
      could be overlooked by conventional methods. Methanol, fatty acids and/or lipids,
      glutamine, phenylalanine, starch, and nucleic acids were more abundant in eli1
      than in WT. Pentaglycine was present in A. thaliana seedlings and more abundant
      in eli1 than in WT.

PMID- 25855561
TI  - Psychogenic tremor in Parkinson's disease.

PMID- 25855562
TI  - Tethered spinal cord: a rare cause of foot deformities.

PMID- 25855563
TI  - Indications and selection of MR enterography vs. MR enteroclysis with emphasis on
      patients who need small bowel MRI and general anaesthesia: results of a survey.
AB  - AIMS: To survey the perceived indications for magnetic resonance imaging of the
      small bowel (MRE) by experts, when MR enteroclysis (MREc) or MR enterography
      (MREg) may be chosen, and to determine how the approach to MRE is modified when
      general anaesthesia (GA) is required. MATERIALS AND METHODS: Selected opinion
      leaders in MRE completed a questionnaire that included clinical indications (MREg
      or MREc), specifics regarding administration of enteral contrast, and how the
      technique is altered to accommodate GA. RESULTS: Fourteen responded. Only the
      diagnosis and follow-up of Crohn's disease were considered by over 80 % as a
      valid MRE indication. The remaining indications ranged between 35.7 % for
      diagnosis of caeliac disease and unknown sources of gastrointestinal bleeding to
      78.6 % for motility disorders. The majority chose MREg over MREc for all
      indications (from 100 % for follow-up of caeliac disease to 57.7 % for tumour
      diagnosis). Fifty per cent of responders had needed to consider MRE under GA. The
      most commonly recommended procedural change was MRI without enteral distention.
      Three had experience with intubation under GA (MREc modification). CONCLUSION:
      Views were variable. Requests for MRE under GA are not uncommon. Presently most
      opinion leaders suggest standard abdominal MRI when GA is required. MAIN
      MESSAGES: * Experts are using MRE for various indications. * Requests for MRE
      under general anaesthesia are not uncommon. * Some radiologists employ MREc under
      general anaesthesia; others do not distend the small bowel.

PMID- 25855564
TI  - Morphological MR imaging of the articular cartilage of the knee at 3 T-comparison
      of standard and novel 3D sequences.
AB  - OBJECTIVES: This study sought to compare various 3D cartilage sequences and to
      evaluate the usefulness of ultrashort TE (UTE) imaging, a new technique to
      isolate signal from the osteochondral junction. METHODS: Twenty knees were
      examined at 3 T with 3D spoiled GRE (FLASH), double-echo steady-state (DESS),
      balanced SSFP, 3D turbo spin-echo (TSE), and a prototype UTE sequence. Two
      radiologists independently evaluated all images. Consensus readings of all
      sequences were the reference standard. Statistical analysis included Friedman and
      pairwise Wilcoxon tests. Retrospective analysis of UTE morphology of
      osteochondral tissue in normal and abnormal cartilage seen at conventional MR was
      also performed. RESULTS: Three-dimensional TSE was superior to other sequences
      for detecting cartilage lesions. FLASH and DESS performed best in the subjective
      quality analysis. On UTE images, normal cartilage exhibited a high-intensity
      linear signal near the osteochondral junction. Retrospective analysis revealed
      abnormal UTE morphology of the osteochondral junction in 50 % of cartilage
      lesions diagnosed at conventional MR. CONCLUSIONS: Cartilage imaging of the knee
      at 3 T can be reliably performed using 3D TSE, showing high accuracy when
      compared to standard sequences. Although UTE depicts signal from the deep
      cartilage layer, further studies are needed to establish its role for assessment
      of cartilage. MAIN MESSAGES: * MRI is the best available imaging method for
      assessment of knee cartilage. * Cartilage imaging can be reliably performed using
      3D TSE. * UTE cannot be used as a single sequence to assess cartilage.

PMID- 25855565
TI  - The microcapsule-type formaldehyde scavenger: the preparation and the application
      in urea-formaldehyde adhesives.
AB  - The limitation and regulation of formaldehyde emissions (FE) now shows great
      importance in wood-based materials such as plywood and particle board
      manufactured for building and furnishing materials. The widely used formaldehyde
      based adhesives are one of the main sources of FE from the wood products. In this
      work, a new kind of long-term effective formaldehyde scavenger in the
      microcapsule form was prepared by using an intra-liquid desiccation method. The
      characterizations of the capsule (UC) were performed including the morphologies,
      the yields, the loading efficiency as well as its sustained-release of urea in
      aqueous conditions. The prepared UC could be integrated in urea-formaldehyde
      resins by simply physical blending, and the mixtures were available to be applied
      as the adhesives for the manufacture of plywood. The bonding strength (BS) and
      the FE of the bonded plywood in both short (3h) and long (12 week) period were
      evaluated in detail. It was found that the FE profile of the plywood behaved
      following a duple exponential law within 12 week. The addition of UC in the
      adhesive can effectively depress the FE of the plywood not only in a short period
      after preparation but also in a long-term period during its practical
      application. The slow released urea would continuously suppress the emission of
      toxic formaldehyde in a sustained manner without obviously deteriorating on the
      BS of the adhesives. 

PMID- 25855566
TI  - Coagulation of methylated arsenic from drinking water: Influence of methyl
      substitution.
AB  - Methylated arsenic can be found in virtually all earth surface environments. So
      far, however, little information has been collected regarding their removal by
      coagulation. In this study, the removal of monomethylarsenate (MMA) and
      dimethylarsenate (DMA) from drinking water by coagulation was investigated from
      the viewpoint of methyl substitution. Results indicated that FeCl3 was more
      efficient than AlCl3 and polyaluminum chloride (PACl) in methylated As removal.
      For the initial arsenic concentration of 200 MUg/L, an FeCl3 dosage of 0.2 mmol
      Fe/L was sufficient to attain about 95% removal of MMA, while a dosage of 0.6
      mmol Fe/L achieved about 57% removal of DMA. Arsenic removal efficiency was
      negatively correlated with the degree of methyl substitution. With the increase
      in methyl group number, the quantity of negatively charged arsenic species
      decreased and molecular size increased, leading to the decrease of methylated As
      removal by coagulation. Adsorption on preformed hydroxide flocs was the major
      mechanism during coagulation. Both FTIR and XPS results indicated that the As-O
      group of As might substitute the O-H group of Fe/Al hydroxide to form a Fe/Al-O
      As complex. Furthermore, the use of traditional oxidants and coagulation aids
      exhibited limited help for improving coagulation removal of DMA.

PMID- 25855567
TI  - Simultaneous removal of methylene blue and copper(II) ions by photoelectron
      catalytic oxidation using stannic oxide modified iron(III) oxide composite
      electrodes.
AB  - Stannic oxide modified Fe(III) oxide composite electrodes (SnO2/Fe2O3) were
      synthesized for simultaneously removing methylene blue (MB) and Cu(II) from
      wastewater using photoelectron catalytic oxidation (PEO). The SnO2/Fe2O3
      electrodes were characterized using scanning electron microscopy (SEM), X-ray
      diffraction (XRD), and photoelectrochemical techniques. The removal of MB and
      Cu(II) by PEO using the SnO2/Fe2O3 composite electrodes was studied in terms of
      reaction time, electric current density, and pH of the electrolyte. The kinetics
      of the reactions were investigated using batch assays. The optimal reaction time,
      pH, and electric current density of the PEO process were determined to be 30 min,
      6.0, and 10 mA/cm(2), respectively. The removal rates of MB from wastewater
      treated by PEO and electron catalytic oxidation process were 84.87% and 70.64%,
      respectively, while the recovery rates of Cu(II) were 91.75% and 96.78%,
      respectively. The results suggest that PEO is an effective method for the
      simultaneous removal of MB and Cu(II) from wastewater, and the PEO process
      exhibits a much higher removal rate for MB and Cu(II) compared to the electron
      catalytic oxidation process. Furthermore, the removal of MB was found to follow
      the Langmuir-Freundlich-Hinshelwood kinetic model, whereas the removal of Cu(II)
      fitted well to the first-order reaction model.

PMID- 25855568
TI  - A facile one-step electrochemical strategy of doping iron, nitrogen, and fluorine
      into titania nanotube arrays with enhanced visible light photoactivity.
AB  - Highly ordered iron, nitrogen, and fluorine tri-doped TiO2 (Fe, (N, F)-TiO2)
      nanotube arrays were successfully synthesized by a facile one-step
      electrochemical method in an NH4F electrolyte containing Fe ions. The morphology,
      structure, composition, and photoelectrochemical property of the as-prepared
      nanotube arrays were characterized by various methods. The photoactivities of the
      samples were evaluated by the degradation of phenol in an aqueous solution under
      visible light. Tri-doped TiO2 showed higher photoactivities than undoped TiO2
      under visible light. The optimum Fe(3+) doping amount at 0.005M exhibited the
      highest photoactivity and exceeded that of undoped TiO2 by a factor of 20 times
      under visible light. The formation of N 2p level near the valence band (VB)
      contributed to visible light absorption. Doping fluorine and appropriate Fe(3+)
      ions reduced the photogenerated electrons-holes recombination rate and enhanced
      visible light photoactivity. The X-ray photoelectron spectroscopy (XPS) and
      Fourier transform infrared spectroscopy (FTIR) results indicated the presence of
      synergistic effects in Fe, N, and F tri-doped TiO2, which enhanced visible light
      photoactivity. The Fe, (N, F)-TiO2 photocatalyst exhibited high stability.

PMID- 25855569
TI  - A hybridization approach to efficient TiO2 photodegradation of aqueous
      benzalkonium chloride.
AB  - TiO2 get positively charged upon UV-irradiation and repel the cationic pollutants
      away from the surface. Hybridization of AC onto TiO2 (ACT) tends catalyst surface
      negatively charged besides providing highly favorable adsorptions sites for
      cationic pollutants. The photodegradation of benzalkonium chloride (BKC), a
      quaternary ammonium surfactant and a pharmaceutical, is investigated with ACT.
      The surface charge of the catalyst in surfactant and non-surfactant aqueous
      dispersion under UV-irradiation is investigated and explained. The anomalous
      increase in COD values at the beginning of BKC-photodegradation is explained. The
      intermediate products formed are identified in both solution and solid phase.
      Trace amount of dodecane remained adsorbed on the catalyst surface after 1h UV
      irradiation, but complete mineralization of BKC is achieved with 2h UV
      irradiation. We propose that BKC photodegradation starts by central fission of
      benzyl CN bond followed by dealkylation, and demethylation steps. 

PMID- 25855570
TI  - Adiposity Measurements and Non-Surgical Periodontal Therapy Outcomes.
AB  - BACKGROUND: Obesity is considered a risk factor for periodontitis. However, its
      influence on periodontal therapy has not been clearly determined. The aim of this
      case-control study is to evaluate the association between adiposity measurements,
      non-surgical periodontal treatment outcomes, and influencing factors in patients
      with chronic periodontitis. METHODS: Eighteen obese and 18 normal-weight (NW)
      patients are included in this study. The waist/hip ratio (WHR), plaque index,
      bleeding on probing, probing depth (PD), and clinical attachment level (CAL) were
      measured at baseline and 3 and 6 months after treatment. Univariable and
      multivariable analyses were used to evaluate the influence of sex, age, baseline
      percentage of PD >3 mm, WHR, and obesity on periodontal treatment outcomes.
      RESULTS: Demographic and periodontal characteristics at baseline were similar in
      both groups. All periodontal parameters were improved during treatment in both
      groups. PD reduction and CAL gain were 0.88 and 0.84 mm in NW individuals and
      0.79 and 0.68 mm in obese individuals. The difference in moderate-to-deep pocket
      (PD >5 mm) percentages between the baseline and 6-month examinations was 9.1% in
      NW individuals and 6.08% for obese individuals. Multivariable analysis showed
      that obesity negatively influenced changes of PD >5 mm percentages. This
      influence was also observed at 3 months for improving sites (PD decrease >2 mm
      between examinations) if WHR was also considered in the analysis. CONCLUSIONS: A
      negative association between adiposity measurements and periodontal treatment
      outcomes was observed mainly for moderate-to-deep pockets. Consideration of WHR
      and other influencing factors amplified the negative effect of obesity on
      periodontal treatment outcomes.

PMID- 25855571
TI  - Osteocytic Sclerostin Expression in Alveolar Bone in Rats With Diabetes Mellitus
      and Ligature-Induced Periodontitis.
AB  - BACKGROUND: Osteocytic sclerostin inhibits bone formation, and its expression is
      stimulated by tumor necrosis factor (TNF)-alpha. This study investigates
      sclerostin and TNF-alpha expression in rats with diabetes mellitus (DM) and
      periodontitis. METHODS: Rats were divided into control (C), periodontitis (P),
      and DM + periodontitis (DP) groups. After induction of DM by streptozotocin,
      periodontitis was induced by ligature. At day 0 (control) and at days 3 and 20
      after induction of periodontitis, alveolar bone, osteoclasts, osteoid area, and
      TNF-alpha and sclerostin expression were evaluated. RESULTS: The distance between
      the cemento-enamel junction and the alveolar bone crest of the DP group was
      longer than that of the P group at day 20 after induction of periodontitis, but
      the number of osteoclasts was not different. Osteoid area decreased in both the P
      and DP groups by day 3, but whereas sustained osteoid suppression was observed in
      the DP group at day 20, osteoid formation was increased in the P group. The
      number of sclerostin-positive osteocytes increased in both groups at day 3, but
      the increased number of sclerostin-positive osteocytes was maintained only in the
      DP group through day 20. The number of TNF-alpha-positive cells increased more in
      the DP group than in the P group. CONCLUSIONS: Enhanced alveolar bone loss,
      suppressed bone formation, and prevalent TNF-alpha expression were characteristic
      of the DP group compared with the P group. Suppressed bone formation in the DP
      group was observed simultaneously with increased sclerostin and TNF-alpha
      expression. These results suggest that upregulated osteocytic sclerostin
      expression in periodontitis accompanied by DM may play a role in suppressed bone
      formation.

PMID- 25855572
TI  - The Interaction Between beta-3 Adrenergic Receptor and Peroxisome Proliferator
      Activated Receptor Gamma Gene Polymorphism to Periodontal Disease in Community
      Dwelling Elderly Japanese.
AB  - BACKGROUND: It has been hypothesized that beta-3 adrenergic receptor and
      peroxisome proliferator-activated receptor gamma (PPARgamma) might have gene
      environmental and gene-gene interactions in periodontal disease. The purpose of
      this study is to elucidate the interaction between beta-3 adrenergic receptor and
      PPARgamma gene polymorphism with periodontal disease. METHODS: Three hundred
      thirty-two postmenopausal females were enrolled, and their serum high-sensitivity
      C-reactive protein (hsCRP) and hemoglobin A1c (HbA1c) were examined. beta-3
      adrenergic receptor and PPARgamma genotypes were then determined. An oral
      examination was performed. The number of remaining teeth was counted, and the
      probing depth (PD) and clinical attachment level (CAL) were measured. Prevalence
      rate ratios (PRRs) were calculated by multiple Poisson regression analyses to
      evaluate the relationship among periodontal disease markers, such as the number
      of sites with CAL 4 to 5 or >=6 mm or PD 4 to 5 or >=6 mm, and beta-3 adrenergic
      receptor polymorphisms, PPARgamma polymorphisms, and the interaction term
      adjusted by age, hsCRP, and HbA1c, after converting the number of remaining teeth
      (n) to an offset variable. RESULTS: In the participants with body mass index
      (BMI) >=25, PRRs of beta-3 adrenergic receptor genotype (Trp/Arg and Arg/Arg) for
      periodontal disease markers were 0.13 to 0.70 (P <0.0001 to 0.74), those of
      PPARgamma genotype (Pro/Pro) were 0.66 to 3.14 (P = 0.01 to 0.68), and those of
      the interaction term for the two genotypes were 1.69 to 12.61 (P <0.0001 to
      0.33). However, in the participants with BMI <25, a constant tendency was not
      observed. CONCLUSION: The results confirmed a positive relationship between the
      interaction term for beta-3 adrenergic receptor genotype and PPARgamma genotype
      and various periodontal markers in obese elderly females.

PMID- 25855573
TI  - Preventing and Treating Peri-Implantitis: A Cost-Effectiveness Analysis.
AB  - BACKGROUND: A large number of treatments for peri-implantitis are available, but
      their cost-effectiveness remains uncertain. This study evaluates the cost
      effectiveness of preventing and treating peri-implantitis. METHODS: A Markov
      model was constructed that followed each implant over 20 years. Supportive
      implant therapy (SIT) for managing peri-implant mucositis and preventing
      development of peri-implantitis was either provided or not. Risk of peri
      implantitis was assumed to be affected by SIT and the patient's risk profile. If
      peri-implantitis occurred, 11 treatment strategies (non-surgical or surgical
      debridement alone or combined with adjunct therapies) were compared. Treatments
      and risk profiles determined disease progression. Modeling was performed based on
      systematically collected data. Primary outcomes were costs and proportion of lost
      implants, as assessed via Monte Carlo microsimulations. RESULTS: Not providing
      SIT and performing only non-surgical debridement was both least costly and least
      effective. The next best (more costly and effective) option was to provide SIT
      and perform surgical debridement (additional 0.89 euros per 1% fewer implants
      lost). The most effective option included bone grafts, membranes, and laser
      treatment (56 euros per 1%). For patients at high risk, the cost-effectiveness of
      SIT increased, whereas in low-risk groups, a cost-optimized strategy was cost
      effective. CONCLUSIONS: Although clinical decision-making will be guided mainly
      by clinical condition, cost-effectiveness analyses might add another perspective.
      Based on these findings, an unambiguous comparative effectiveness ranking was not
      established. However, cost-effectiveness was predominantly determined by
      provision of SIT and initial treatment costs. Transferability of these findings
      to other healthcare systems needs further confirmation.

PMID- 25855574
TI  - Genetic evolution in immunization.

PMID- 25855575
TI  - Prevalence of Barrett's Esophagus in Bariatric Patients Undergoing Sleeve
      Gastrectomy.
AB  - BACKGROUND: The appearance and incidence of gastroesophageal reflux after sleeve
      gastrectomy is not yet resolved, and there is an important controversy in the
      literature. No publications regarding the appearance of Barrett's esophagus after
      sleeve gastrectomy are present in the current literature. PURPOSE: The purpose of
      this paper was to report the incidence of Barrett's esophagus in patients
      submitted to sleeve. MATERIAL AND METHODS: Two hundred thirty-one patients are
      included in this study who were submitted to sleeve gastrectomy for morbid
      obesity. None had Barrett's esophagus. Postoperative upper endoscopy control was
      routinely performed 1 month after surgery and 1 year after the operation, all
      completed the follow-up in the first year, 188 in the second year, 123 in the
      third year, 108 in the fifth year, and 66 patients over 5 years after surgery.
      RESULTS: Among 231 patients operated on and followed clinically, reflux symptoms
      were detected in 57 (23.2%). Erosive esophagitis was found in 38 patients
      (15.5%), and histological examination confirmed Barrett's esophagus in 3/231
      cases (1.2%) with presence of intestinal metaplasia. CONCLUSION: Bariatric
      surgeons should be aware of the association of gastroesophageal reflux (GER)
      disease and obesity. Appropriate bariatric surgery should be indicated in order
      to prevent the occurrence of esophagitis and Barrett's esophagus.

PMID- 25855576
TI  - Bioinspired hybrid materials from spray-formed ceramic templates.
AB  - Thermally sprayed ceramics, when infiltrated with polymer, exhibit synergistic
      increases in strength and toughness. The structure of such composites-a dense,
      brick-mortar arrangement-is strikingly similar to that of nacre, as are the
      mechanisms underlying the robust mechanical behavior. This industrial-scale
      process thus presents an exciting tool for bio-mimetic exploration. 

PMID- 25855577
TI  - Pretreatment and Treatment With L-Arginine Attenuate Weight Loss and Bacterial
      Translocation in Dextran Sulfate Sodium Colitis.
AB  - BACKGROUND: Imbalances in a variety of factors, including genetics, intestinal
      flora, and mucosal immunity, can contribute to the development of ulcerative
      colitis and its side effects. This study evaluated the effects of pretreatment or
      treatment with arginine by oral administration on intestinal permeability,
      bacterial translocation (BT), and mucosal intestinal damage due to colitis.
      METHODS: C57BL/6 mice were distributed into 4 groups: standard diet and water (C:
      control group), standard diet and dextran sodium sulfate (DSS) solution (Col:
      colitis group), 2% L-arginine supplementation for 7 days prior to DSS
      administration and during disease induction (PT: pretreated group), and 2% L
      arginine supplementation during disease induction (T: treated group). Colitis was
      induced by administration of 1.5% DSS for 7 days. After 14 days, intestinal
      permeability and BT were evaluated; colons were collected for histologic analysis
      and determination of cytokines; feces were collected for measurement of
      immunoglobulin A (IgA). RESULTS: The Col group showed increased intestinal
      permeability (C vs Col: P < .05) and BT (C vs Col: P < .05). In the arginine
      supplemented groups (PT and T), this amino acid tended to decrease intestinal
      permeability. Arginine decreased BT to liver during PT (P < .05) and to blood,
      liver, spleen, and lung during T (P < .05). Histologic analysis showed that
      arginine preserved the intestinal mucosa and tended to decreased inflammation.
      CONCLUSIONS: Arginine attenuates weight loss and BT in mice with colitis.

PMID- 25855578
TI  - Comparison Between Handgrip Dynamometry and Manual Muscle Testing Performed by
      Registered Dietitians in Measuring Muscle Strength and Function of Hospitalized
      Patients.
AB  - BACKGROUND: The Academy of Nutrition and Dietetics and American Society the
      Parenteral and Enteral Nutrition (ASPEN) Consensus Statement recommends a
      standardized set of diagnostic characteristics to identify adult malnutrition.
      Due to lack of a consensus definition and challenges with measurements, physical
      function or performance has traditionally been difficult to assess. The purpose
      of this study was to determine whether manual muscle testing (MMT) performed by
      registered dietitians (RDs) can be used as a surrogate measurement of muscle
      strength and function in hospitalized patients. METHOD: Patients admitted to the
      heart failure service on the cardiac stepdown units at the Cleveland Clinic Main
      Campus in Cleveland, Ohio, were eligible for the study, and those who met the
      inclusion criteria underwent handgrip strength (HGS) testing and evaluation of
      nutrition status using the Academy/ASPEN Characteristics Recommended for the
      Identification of Adult Malnutrition. MMT was then performed within 24 hours by a
      different study investigator blinded to the HGS and malnutrition assessment
      results. RESULTS: It was found that HGS and MMT overall were in agreement for 84%
      of patients and that MMT had a high sensitivity (98%) but low specificity (13%).
      CONCLUSION: This study shows feasibility for RDs to perform MMT on patients to
      determine muscle strength and functioning. Future practice application may be to
      incorporate MMT into screening criteria for patients being evaluated for
      malnutrition and reserve HGS testing only for patients with an abnormal MMT.

PMID- 25855579
TI  - Thyroid cancer GWAS identifies 10q26.12 and 6q14.1 as novel susceptibility loci
      and reveals genetic heterogeneity among populations.
AB  - Thyroid cancer is the most heritable cancer of all those not displaying typical
      Mendelian inheritance. However, most of the genetic factors that would explain
      the high heritability remain unknown. Our aim was to identify additional common
      genetic variants associated with susceptibility to this disease. In order to do
      so, we performed a genome-wide association study in a series of 398 cases and 502
      controls from Spain, followed by a replication in four well-defined Southern
      European case-control collections contributing a total of 1,422 cases and 1,908
      controls. The association between the variation at the 9q22 locus near FOXE1 and
      thyroid cancer risk was consistent across all series, with several SNPs
      identified (rs7028661: OR = 1.64, p = 1.0 * 10(-22) , rs7037324: OR = 1.54, p =
      1.2 * 10(-17) ). Moreover, the rare alleles of three SNPs (rs2997312, rs10788123
      and rs1254167) at 10q26.12 showed suggestive evidence of association with higher
      risk of the disease (OR = 1.35, p = 1.2 * 10(-04) , OR = 1.26, p = 5.2 * 10(-04)
      and OR = 1.38, p = 5.9 * 10(-05) , respectively). Finally, the rare allele of
      rs4075570 at 6q14.1 conferred protection in the series studied (OR = 0.82, p =
      2.0 * 10(-04) ). This study suggests that heterogeneity in genetic susceptibility
      between populations is a key feature to take into account when exploring genetic
      risk factors related to this disease. 

PMID- 25855580
TI  - Perturbations in inter-domain associations may trigger the onset of pathogenic
      transformations in PrP(C): insights from atomistic simulations.
AB  - Conversion of the predominantly alpha-helical cellular prion protein (PrP(C)) to
      the misfolded beta-sheet enriched Scrapie form (PrP(Sc)) is a critical event in
      prion pathogenesis. However, the conformational triggers that lead to the isoform
      conversion (PrP(C) to PrP(Sc)) remain obscure, and conjectures about the role of
      unusually hydrophilic, short helix H1 of the C-terminal globular domain in the
      transition are varied. Helix H1 is anchored to helix H3 via a few stabilizing
      polar interactions. We have employed fully atomistic molecular dynamics
      simulations to study the effects triggered by a minor perturbation in the network
      of these non-bonded interactions in PrP(C). The elimination of just one of the
      key H1-H3 hydrogen bonds led to a cascade of conformational changes that are
      consistent with those observed in partially unfolded intermediates of PrP(C),
      with pathogenic mutations and in low pH environments. Our analyses reveal that
      the perturbation results in the enhanced conformational flexibility of the
      protein. The resultant enhancement in the dynamics leads to overall increased
      solvent exposure of the hydrophobic core residues and concomitant disruption of
      the H1-H3 inter-domain salt bridge network. This study lends credence to the
      hypothesis that perturbing the cooperativity of the stabilizing interactions in
      the PrP(C) globular domain can critically affect its dynamics and may lead to
      structural transitions of pathological relevance. 

PMID- 25855581
TI  - Development of hepatocellular carcinoma in cardiac congestive liver fibrosis:
      report of a case.
AB  - We report an extremely rare case of the development of hepatocellular carcinoma
      (HCC) in cardiac congestive liver fibrosis. A 62-year-old female presented to our
      hospital with a complaint of right upper quadrant pain. The patient had undergone
      cardiac surgery for pulmonary valve insufficiency, pulmonary stenosis and atrial
      septal defect when she was fifteen years of age. During the subsequent 47 years,
      she had occasionally suffered from various symptoms associated with right-sided
      heart failure due to pulmonary stenosis. Computed tomography revealed a liver
      tumor measuring 63 mm in diameter in segment 5 and other liver tumors in segments
      5 (18 mm), 8 (17 mm) and 4 (12 mm), which were diagnosed as HCCs. There was no
      evidence of stenosis in any hepatic veins or inferior vena cava, and no
      infectious hepatitis or alcoholic liver damage. Anterior sectionectomy and
      partial resection of segment 4 was performed, and histological examination showed
      that these tumors were HCC accompanied by congestive liver fibrosis. Nine months
      later, multiple recurrent HCCs were detected in segment 6, and transcatheter
      arterial chemoembolization was employed thereafter. The patient died 40 months
      after surgery due to advanced recurrence. 

PMID- 25855583
TI  - Inducing magnetic communication in caged dinuclear Co(II) systems.
AB  - The synthesis, structural, electronic and magnetic characterization of five
      dinuclear Co(II) azacryptand compounds (1-5) bridged through different ions are
      reported. The magnetic exchange interactions, 2J values, obtained from
      theoretical computations show that the variation of the intermetallic angles and
      distances lead to antiferromagnetic behaviours. Magneto-structural correlations
      show a trend, where the angles Co(II)-bridge-Co(II) closer to 180 degrees  favour
      an increase in the superexchange pathway leading to higher AF interaction values.

PMID- 25855582
TI  - Significant biomarkers for the management of hepatocellular carcinoma.
AB  - Surveillance of hepatocellular carcinoma (HCC) is important for early detection.
      Imaging tests including computed tomography, magnetic resonance imaging and
      ultrasonography with or without various kinds of contrast medium are important
      options for detecting HCC. In addition to the imaging tests, various kinds of
      biomarkers including alpha-fetoprotein (AFP), lectin-bound AFP (AFP-L3) and
      protein induced by vitamin K absence or antagonist II (PIVKA-II) have been widely
      used to detect HCC and analyze treatment response. Recently, various kinds of
      novel biomarkers (proteins and miRNA) have been found to predict the malignancy
      potential of HCC and treatment response to specific therapies. Moreover, various
      combinations of well-established biomarkers and novel biomarkers have been tested
      to improve sensitivity and specificity. In practical terms, biomarkers that can
      be analyzed using peripheral blood samples might be more useful than
      immunohistochemical techniques. It has been reported that quantification of
      cytokines in peripheral blood and the analysis of peripheral immune subsets could
      be good biomarkers for managing HCC. Here, we describe the usefulness of and
      update well-established and novel biomarkers for the management of HCC. 

PMID- 25855585
TI  - Divergent construction of pyrazoles via Michael addition of N-arylhydrazones to
      1,2-diaza-1,3-dienes.
AB  - The base (NaH)-promoted Michael addition of N-arylhydrazones (AHs) with 1,2-diaza
      1,3-dienes (DDs) produces unprecedented beta-azohydrazone adducts. Strategically,
      the use of AHs as acyl anion equivalents (d(1) synthon) and DDs as alpha
      electrophiles (a(2) synthon) of carbonyl compounds open the way to two important
      classes of pyrazole compounds. 

PMID- 25855584
TI  - Protective Effects and Mechanisms of Salvianolic Acid B Against H2O2-Induced
      Injury in Induced Pluripotent Stem Cell-Derived Neural Stem Cells.
AB  - Induced pluripotent stem cells (iPSCs) have the potential to differentiate into
      neural lineages. Salvianolic acid B (Sal B) is a commonly used, traditional
      Chinese medicine for enhancing neuroprotective effects, and has antioxidant, anti
      inflammatory, and antiapoptotic properties. Here, we explore the potential
      mechanism of Sal B in protecting iPSC-derived neural stem cells (NSCs) against
      H2O2-induced injury. iPSCs were induced into NSCs, iPSC-derived NSCs were treated
      with 50 MUM Sal B for 24.5 h and 500 MUM H2O2 for 24 h. The resulting effects
      were examined by flow cytometry analysis, quantitative reverse-transcription
      polymerase chain reaction, and western blotting. Upon H2O2 exposure, Sal B
      significantly promoted cell viability and stabilization of the mitochondrial
      membrane potential. Sal B also visibly decreased the cell apoptotic ratio. In
      addition, Sal B markedly reduced expression of matrix metalloproteinase (MMP)-2
      and -9, and phosphospecific signal transducer and activator of transcription 3 (p
      STAT3), and increased the level of tissue inhibitor of metalloproteinase (TIMP)-2
      in iPSC-derived NSCs induced by H2O2. These results suggest that Sal B protects
      iPSC-derived NSCs against H2O2-induced oxidative stress. The mechanisms of this
      stress tolerance may be attributed to modulation of the MMP/TIMP system and
      inhibition of the STAT3 signaling pathway.

PMID- 25855586
TI  - Technical Issues Behind Molecular Monitoring in Chronic Myeloid Leukemia.

PMID- 25855588
TI  - Synthesis of beta-Amino-alpha,beta-unsaturated Ketone Derivatives via Sequential
      Rhodium-Catalyzed Sulfur Ylide Formation/Rearrangement.
AB  - In the presence of a Rh(II) catalyst and beta-(methylthio)-alpha,beta-unsaturated
      ketones, 1-sulfonyl-1,2,3-triazoles can be converted into functionalized beta
      amino-alpha,beta-unsaturated ketones via formation of alpha-imino rhodium
      carbene/sulfur ylide and subsequent rearrangement. The products decompose to
      useful 2-methylthiopyrrole derivatives conveniently in high yield. 

PMID- 25855587
TI  - Oil droplet ingestion and oil fouling in the copepod Calanus finmarchicus exposed
      to mechanically and chemically dispersed crude oil.
AB  - The rates of ingestion of oil microdroplets and oil fouling were investigated in
      the zooplankton filter-feeder Calanus finmarchicus (Gunnerus, 1770) at 3
      concentrations of oil dispersions ranging from 0.25 mg/L to 5.6 mg/L. To compare
      responses to mechanically and chemically dispersed oil, the copepods were exposed
      to comparable dispersions of micron-sized oil droplets made with and without the
      use of a chemical dispersant (similar oil droplet size range and oil
      concentrations) together with a constant supply of microalgae for a period of 4
      d. The filtration rates as well as accumulation of oil droplets decreased with
      increasing exposure concentration. Thus the estimated total amount of oil
      associated with the copepod biomass for the 2 lowest exposures in the range 11
      mL/kg to 17 mL/kg was significantly higher than the approximately 6 mL/kg found
      in the highest exposure. For the 2 lowest concentrations the filtration rates
      were significantly higher in the presence of chemical dispersant. Furthermore, a
      significant increase in the amount of accumulated oil in the presence of
      dispersant was observed in the low exposure group.

PMID- 25855589
TI  - Tissue-type plasminogen activator-binding RNA aptamers inhibiting low-density
      lipoprotein receptor family-mediated internalisation.
AB  - Recombinant tissue-type plasminogen activator (tPA, trade name Alteplase),
      currently the only drug approved by the US Food and Drug Administration and the
      European Medicines Agency for the treatment of cerebral ischaemic stroke, has
      been implicated in a number of adverse effects reportedly mediated by
      interactions with the low-density lipoprotein (LDL) family receptors, including
      neuronal cell death and an increased risk of cerebral haemorrhage. The tissue
      type plasminogen activator is the principal initiator of thrombolysis in human
      physiology, an effect that is mediated directly via localised activation of the
      plasmin zymogen plasminogen at the surface of fibrin clots in the vascular lumen.
      Here, we sought to identify a ligand to tPA capable of inhibiting the relevant
      LDL family receptors without interfering with the fibrinolytic activity of tPA.
      Systematic evolution of ligands by exponential enrichment (SELEX) was employed to
      isolate tPA-binding RNA aptamers, which were characterised in biochemical assays
      of tPA association to low density lipoprotein receptor-related protein-1 (LRP-1,
      an LDL receptor family member); tPA-mediated in vitro and ex vivo clot lysis; and
      tPA-mediated plasminogen activation in the absence and presence of a stimulating
      soluble fibrin fragment. Two aptamers, K18 and K32, had minimal effects on clot
      lysis, but were able to efficiently inhibit tPA-LRP-1 association and LDL
      receptor family-mediated endocytosis in human vascular endothelial cells and
      astrocytes. These observations suggest that coadministration alongside tPA may be
      a viable strategy to improve the safety of thrombolytic treatment of cerebral
      ischaemic stroke by restricting tPA activity to the vascular lumen. 

PMID- 25855590
TI  - Bone marrow mesenchymal stem cell transplantation retards the natural senescence
      of rat hearts.
AB  - Bone marrow mesenchymal stem cells (BMSCs) have been shown to offer a wide
      variety of cellular functions including the protective effects on damaged hearts.
      Here we investigated the antiaging properties of BMSCs and the underlying
      mechanism in a cellular model of cardiomyocyte senescence and a rat model of
      aging hearts. Neonatal rat ventricular cells (NRVCs) and BMSCs were cocultured in
      the same dish with a semipermeable membrane to separate the two populations.
      Monocultured NRVCs displayed the senescence-associated phenotypes, characterized
      by an increase in the number of beta-galactosidase-positive cells and decreases
      in the degradation and disappearance of cellular organelles in a time-dependent
      manner. The levels of reactive oxygen species and malondialdehyde were elevated,
      whereas the activities of antioxidant enzymes superoxide dismutase and
      glutathione peroxidase were decreased, along with upregulation of p53,
      p21(Cip1/Waf1), and p16(INK4a) in the aging cardiomyocytes. These deleterious
      alterations were abrogated in aging NRVCs cocultured with BMSCs. Qualitatively,
      the same senescent phenotypes were consistently observed in aging rat hearts.
      Notably, BMSC transplantation significantly prevented these detrimental
      alterations and improved the impaired cardiac function in the aging rats. In
      summary, BMSCs possess strong antisenescence action on the aging NRVCs and hearts
      and can improve cardiac function after transplantation in aging rats. The present
      study, therefore, provides an alternative approach for the treatment of heart
      failure in the elderly population. 

PMID- 25855592
TI  - Geographical Inequalities in Alcohol-Related Mortality Rates in Taiwan due to
      Socio-Demographic Differences.
AB  - AIMS: To assess the relationships between alcohol-related mortality and socio
      demography in Taiwan. METHODS: Using 2002-2006 data from the national death
      diagnosis registration system, we calculated the alcohol-attributed disease
      mortality of those aged 15 and older in 348 townships in Taiwan. This study
      provides spatial clustering of alcohol-attributed disease mortality rates and
      area socio-demographic conditions across townships, examining the relationship
      between the two using a spatial autoregressive model. RESULTS: The relative risk
      of death due to alcohol-attributed diseases was estimated to increase by 2.1 and
      0.9% as a result of a 1% increase in the percentage of men and aboriginal
      residents, respectively. The risk of death was estimated to decrease by 25% for
      every 1 year increase in education level. Industrialization and labor
      participation were also found to be predictors of the outcome measure in areas
      with differing levels of urbanization. CONCLUSIONS: This study provides
      significant evidence that township-level relationships between alcohol-related
      mortality and socioeconomic variables exist in Taiwan. Public health policymakers
      should better prioritize the specific areas in which comprehensive intervention
      should be undertaken accordingly.

PMID- 25855591
TI  - The association between thyroid autoantibodies in serum and abnormal function and
      structure of the thyroid.
AB  - OBJECTIVES: To evaluate the association between thyroid autoantibodies and
      abnormalities in thyroid function and structure, and to investigate any risk
      factors. METHODS: A cross-sectional survey was undertaken in Chengdu residents >=
      18 years with no previous thyroid disease. The study participants provided
      demographic and clinical data. Thyroid function and serum concentrations of the
      thyroid autoantibodies antithyroperoxidase antibody (TPOAb) and antithyroglobulin
      antibody (TgAb) were measured. RESULTS: A total of 1334 subjects were included in
      this study. The prevalence of TPOAb and TgAb positivity was significantly higher
      in female than in male subjects. The prevalence of thyroid autoantibodies in
      those with subclinical hypothyroidism and clinical hyper- and hypothyroidism was
      significantly greater than in euthyroid subjects. The concentration of TPOAb and
      TgAb in subjects with both TPOAb and TgAb was significantly higher than in those
      who exhibited only one type of thyroid autoantibody. Using multivariate logistic
      regression analysis, female sex, thyroid volume, thyroid hypo- and
      heteroechogenicity were found to be risk factors for the presence of
      autoantibodies. CONCLUSIONS: Thyroid autoantibodies were common in the general
      population. Women with thyroid enlargement, hypoechogenicity and
      heteroechogenicity might benefit from routine screening for thyroid
      autoantibodies and thyroid function.

PMID- 25855593
TI  - A single-centre 37-year experience with reoperation after primary repair of
      atrioventricular septal defect.
AB  - OBJECTIVES: To evaluate our experience with patients reoperated after primary
      repair of atrioventricular septal defect (AVSD) and identify predictors of poor
      outcome. METHODS: Between 1976 and 2014, 69 patients were reoperated after
      primary repair of partial (n = 28), intermediate (n = 15) or complete (n = 26)
      AVSD. RESULTS: Median age at first reoperation was 62.4 (range, 1.6-845) months,
      median interval to first reoperation was 22.3 (range, 0.2-598) months. Main
      indications for first reoperation included left atrioventricular valve (LAVV)
      pathology (66%), residual septal defect (19%) and left ventricle outflow tract
      obstruction (LVOTO; 4%). Procedures to address LAVV pathology included various
      valvuloplasties in 47 (77%) patients and valve replacement in 14 (23%) patients.
      A second, third, fourth and fifth reoperation was required in 27, 12, 4 and 1
      patient, respectively. Most common procedures were LAVV replacement (LAVVR),
      LVOTO relief, pacemaker implantation and right atrioventricular valve procedure.
      Freedom from reoperation after LAVV valvuloplasty (LAVVP) was 84 and 62% at 1 and
      10 years, respectively. There were 10 early and 4 late deaths. Estimated overall
      survival at 1, 5 and 10 years was 87, 83 and 83%, respectively. Double orifice
      LAVV (DOLAVV) was a risk factor for in-hospital and overall mortality [odds ratio
      (OR) = 14.5; 95% confidence interval (CI) = 1.2-178.7; P = 0.037 and hazard ratio
      (HR) = 6.8; 95% CI = 1.5-31.7; P = 0.015, respectively]. Patients with LAVVP and
      LAVVR differed significantly in overall survival (P = 0.014). At the last follow
      up (median, 9.8; range, 0-34 years), 84% survivors were in New York Heart
      Association Class I or II. CONCLUSIONS: Many patients reoperated after primary
      AVSD repair needed surgical reintervention. LAVV pathology was the most common
      indication for reoperation. DOLAVV was a risk factor for mortality. Particular
      AVSD type did not appear to be a risk factor for mortality or LAVVP failure.
      There is some evidence for the close relationship between LAVV pathology and
      LVOTO in subjects undergoing reoperation after primary AVSD repair as some
      patients with initial LAVV problems needed LVOTO repair later on and vice versa.

PMID- 25855594
TI  - Quality of life after intervention on the thoracic aorta.
AB  - Surgery on the thoracic aorta is challenging and historically associated with
      significant mortality and morbidity. In recent times, there has been increased
      emphasis on the importance of health-related quality of life (HRQOL) measures. It
      is seen as a development beyond isolated markers of outcome such as operative
      mortality and is particularly applicable to aortic surgery given the number of
      asymptomatic patients operated on (for prognostic grounds), and rapidly advancing
      endovascular technologies which require proper assessment. This systematic review
      provides an outline of all available literature detailing HRQOL in patients
      receiving intervention (both open and endovascular) on the thoracic aorta. In
      total, 30 studies were identified encompassing 4746 patients undergoing a variety
      of procedures from aortic root replacement to thoracoabdominal aortic aneurysm
      repair. While there were deficiencies in the underlying literature such as lack
      of baseline HRQOL assessment, the majority of the studies confirm that HRQOL
      after major aortic surgery (including on the elderly and in emergency situations)
      is acceptable and compares well to matched general populations. Strategies for
      improving the HRQOL in aortic surgery are summarized and include the need for
      surgeons to plan cerebral protection methods more carefully and to develop
      operative strategies to avoid reoperation or reintervention, as this is
      associated with deterioration of long-term HRQOL. Randomized studies measuring
      baseline and follow-up HRQOL at specific set points are needed. Innovative
      research methods could be employed in future studies with the aim of correlating
      HRQOL with imaging or physiological/inflammation biomarkers, or other end points
      such as aortic stiffness or wall shear stress to characterize disease progression
      and prognosis. 

PMID- 25855595
TI  - Aortopathy in patients with bicuspid aortic valve stenosis: role of aortic root
      functional parameters.
AB  - OBJECTIVES: We prospectively examined functional characteristics of the aortic
      root and transvalvular haemodynamic flow in order to define factors associated
      with the severity of aortopathy in patients undergoing surgery for bicuspid
      aortic valve (BAV) stenosis. METHODS: A total of 103 consecutive patients with
      BAV stenosis (mean age 61 +/- 9 years, 66% male) underwent aortic valve
      replacement +/- concomitant aortic surgery from January 2012 through March 2014.
      All patients underwent preoperative cardiac magnetic resonance imaging (MRI) in
      order to evaluate the systolic transvalvular flow and the following functional
      parameters: (i) angulation between the left ventricular outflow axis and the
      aortic root, (ii) geometrical orientation of residual aortic valve orifice and
      (iii) BAV cusp fusion pattern. MRI data were used to guide sampling of the
      ascending aorta during surgery [i.e. jet-sample from the area where the flow-jet
      impacts on the aortic wall and control sample from the opposite aortic wall
      (obtained from the aortotomy site)]. Aortopathy was quantified by means of a
      histological sum-score (0 to 21+) in each sample. RESULTS: A significant
      correlation was found between histological sum-score in the jet-sample and the
      angle between the LV outflow axis and the aortic root (r = 0.6, P = 0.007).
      Moreover, there was a linear correlation between proximal aortic diameter and the
      angle between systolic flow-jet and ascending aortic wall (r = 0.5, P = 0.006).
      Logistic regression identified the angle between the LV outflow axis and the
      aortic root (OR 1.1, P = 0.04) and the angle between the flow-jet and the aortic
      wall (OR 1.2, P = 0.001) as independent predictors of an indexed proximal aortic
      diameter >=22 mm/m(2). CONCLUSIONS: Functional parameters of the aortic root may
      be used to predict the severity of aortopathy in patients with BAV stenosis, and
      may be useful in predicting future risk of aortic disease in such patients.

PMID- 25855596
TI  - In search of the right study design for bicuspid aortopathy treatment.

PMID- 25855597
TI  - Thoracoscopic ultrasonography for localization of subcentimetre lung nodules.
AB  - OBJECTIVES: Localization of small, non-visible and non-palpable subcentimetre
      nodules can be challenging during video-assisted thoracoscopic surgery (VATS).
      Intraoperative ultrasonography is an option for localization of such lesions, yet
      this technology has not been fully adapted to thoracic surgery. The objective of
      this study was to assess a newly developed thoracoscopic ultrasound for
      localization and biopsy of subcentimetre pulmonary nodules in animal models.
      METHODS: A prototype convex probe ultrasound thoracoscope (XLTF-UC180, Olympus
      Medical Systems Corp.) was used in this study. Multiple 5% agar pseudo-tumours
      were created in porcine lungs (n = 10) and assessed for localization with
      different frequencies (5.0-12.0 MHz) in deflated lungs. The evaluated pseudo
      tumours were divided into two groups based on the distinctness of the tumour
      margin on the ultrasound images and compared in terms of the size and depth of
      the tumours. The visualization of real tumours and the biopsy capability were
      assessed using rabbit VX2 lung tumour models (n = 7). RESULTS: The thoracoscopic
      ultrasound clearly visualized normal lung structures within a 1.5-cm depth
      including small vessels and bronchioles less than 5 mm in diameter in the
      completely deflated lung. Twenty-eight of 30 agar pseudo-tumours (93.3%) were
      successfully detected in deflated lungs (average size: 8.5 +/- 2.1 mm; average
      depth: 7.4 +/- 7.5 mm and depth range: 0-24.8 mm). Two tumours were not detected
      due to residual air surrounding the tumour. Higher frequency (12 MHz) tended to
      show more distinct margins of the targets. Indistinct tumours were located
      significantly deeper in the lung than the distinct tumours (14.11vs 2.42 mm),
      regardless of them being in a similar size range. VX2 tumours were identified as
      heterogeneous isoechoic lesions and adequate tissue sampling for diagnosis was
      achieved using a dedicated needle. CONCLUSIONS: The newly developed convex probe
      ultrasound thoracoscope was capable of localizing subcentimetre nodules in the
      porcine deflated lung as well as of obtaining sufficient sampling from lung
      tumours in the rabbit model, which may enable single-port VATS lung nodule biopsy
      in a human clinical setting. However, the depth of the tumours significantly
      influenced the quality of ultrasound images. Complete collapse of the lung and
      use of high frequency may facilitate achieving distinct visualization of the
      targets.

PMID- 25855598
TI  - Intraoperative diagnosis of lymph node metastasis in non-small-cell lung cancer
      by a semi-dry dot-blot method.
AB  - OBJECTIVES: Sublobar resection procedures, such as segmentectomy and wedge
      resection, can be used for resectable lung cancer when the cancer is small or the
      condition of the patient is poor. In such cases, intraoperative lymph node (LN)
      exploration is necessary to avoid incomplete resection of potential N1 or N2
      disease. The semi-dry dot-blotting (SDB) method was developed to detect
      intraoperative LN metastasis as a quick, cost-effective procedure that does not
      require special technical expertise. This study examined whether SDB can
      sufficiently identify LN metastasis in lung cancer patients. METHODS: This study
      prospectively examined 147 LNs from 50 lung cancer patients who underwent surgery
      at Nagasaki University Hospital between April 2011 and June 2013. The SDB method
      uses antigen-antibody reactions with anti-pancytokeratin as the primary antibody
      and detects cancer cells using chromogen. To identify LN metastases, each LN was
      examined by the SDB method during surgery along with intraoperative pathological
      diagnosis (ope-Dx) and permanent pathological diagnosis (permanent-Dx). RESULTS:
      Compared with permanent-Dx, SDB offered 94.7% sensitivity, 97.7% specificity and
      97.2% accuracy, while ope-Dx exhibited 84.2% sensitivity, 100% specificity and
      98.0% accuracy. For 3 cases, micrometastases were detected by the SDB method but
      not by ope-Dx. Three LNs from lobar stations showed pseudo-positive results by
      the SDB method because of the presence of alveolar epithelium. CONCLUSIONS: The
      SDB method offers acceptably high accuracy in detecting LN metastasis, especially
      for mediastinal LNs, and represents a potential alternative for the
      intraoperative diagnosis of LN metastasis, even in the absence of a pathologist.

PMID- 25855599
TI  - Lung transplantation from donation after cardiocirculatory death: the end of the
      golden era?

PMID- 25855600
TI  - Three-dimensional surface reconstruction and in situ site-specific cutting of the
      teliospores of Puccinia miscanthi causing leaf rust of the biomass plant
      Miscanthus sinensis.
AB  - The rust fungus Puccinia miscanthi on the naturally infected leaves of eulalia
      grass were investigated by light and electron microscopy. Many black telia were
      present on both the adaxial and abaxial leaf surfaces. The telia were often
      confluent, protruding distinctly from the leaf surface, and had numerous
      teliospores. Light microscopy revealed that the teliospores were club-like in
      shape (clavate), chestnut brown, and produced pedicels from one end. They were
      measured to be approximately 45 MUm * 20 MUm in size, and slightly constricted at
      the septa. Using stereo imaging, it was possible to generate images with more
      three-dimensionality than conventional scanning electron micrographs. Without the
      need for the mechanical sectioning of telia, the height of telia from the leaf
      epidermis could be measured at approximately 230 MUm using three-dimensional
      surface reconstruction. Urediniospores were also found on the leaf surface, and
      possessed spines on the surface (echinulate). The internal features of the
      nonembedded teliospores could be unveiled using a focused ion beam system with a
      field emission scanning electron microscope, allowing for the in situ site
      specific cutting of the non-embedded teliospores. These results show that three
      dimensional surface reconstruction and targeted cutting are a potential
      alternative to mechanical sectioning of resin-embedded blocks, and have the
      potential to eliminate the uncertainty involved in selecting the region of
      interest.

PMID- 25855601
TI  - GATA2 is critical for the maintenance of cellular identity in differentiated mast
      cells derived from mouse bone marrow.
AB  - GATA2 plays a crucial role for the mast cell fate decision. We herein demonstrate
      that GATA2 is also required for the maintenance of the cellular identity in
      committed mast cells derived from mouse bone marrow (BMMCs). The deletion of the
      GATA2 DNA binding domain (GATA2DeltaCF) in BMMCs resulted in a loss of the mast
      cell phenotype and an increase in the number of CD11b- and/or Ly6G/C-positive
      cells. These cells showed the ability to differentiate into macrophage- and
      neutrophil-like cells but not into eosinophils. Although the mRNA levels of
      basophil-specific genes were elevated, CD49b, a representative basophil marker,
      never appeared on these cells. GATA2 ablation led to a significant upregulation
      of C/EBPalpha, and forced expression of C/EBPalpha in wild-type BMMCs phenocopied
      the GATA2DeltaCF cells. Interestingly, simultaneous deletion of the Gata2 and
      Cebpa genes in BMMCs restored the aberrant increases of CD11b and Ly6G/C while
      retaining the reduced c-Kit expression. Chromatin immunoprecipitation assays
      indicated that GATA2 directly binds to the +37-kb region of the Cebpa gene and
      thereby inhibits the RUNX1 and PU.1 binding to the neighboring region.
      Upregulation of C/EBPalpha following the loss of GATA2 was not observed in
      cultured mast cells derived from peritoneal fluid, whereas the repression of c
      Kit and other mast cell-specific genes were observed in these cells.
      Collectively, these results indicate that GATA2 maintains cellular identity by
      preventing Cebpa gene activation in a subpopulation of mast cells, whereas it
      plays a fundamental role as a positive regulator of mast cell-specific genes
      throughout development of this cell lineage. 

PMID- 25855602
TI  - The aryl hydrocarbon receptor nuclear translocator is an essential regulator of
      murine hematopoietic stem cell viability.
AB  - Hypoxia-inducible factors (HIFs) are master regulators of the transcriptional
      response to low oxygen and play essential roles in embryonic development, tissue
      homeostasis, and disease. Recent studies have demonstrated that hematopoietic
      stem cells (HSCs) within the bone marrow localize to a hypoxic niche and that HIF
      1alpha promotes HSC adaptation to stress. Because the related factor HIF-2alpha
      is also expressed in HSCs, the combined role of HIF-1alpha and HIF-2alpha in HSC
      maintenance is unclear. To this end, we have conditionally deleted the HIF-alpha
      dimerization partner, the aryl hydrocarbon receptor nuclear translocator (ARNT)
      in the hematopoietic system to ablate activity of both HIF-1alpha and HIF-2alpha
      and assessed the functional consequence of ARNT deficiency on fetal liver and
      adult hematopoiesis. We determined that ARNT is essential for adult and fetal HSC
      viability and homeostasis. Importantly, conditional knockout of both Hif-1alpha
      and Hif-2alpha phenocopied key aspects of these HSC phenotypes, demonstrating
      that the impact of Arnt deletion is primarily HIF dependent. ARNT-deficient long
      term HSCs underwent apoptosis, potentially because of reduced B-cell lymphoma 2
      (BCL-2) and vascular endothelial growth factor A (VEGF-A) expression. Our results
      suggest that HIF activity may regulate HSC homeostasis through these prosurvival
      factors. 

PMID- 25855603
TI  - PAX5 is a tumor suppressor in mouse mutagenesis models of acute lymphoblastic
      leukemia.
AB  - Alterations of genes encoding transcriptional regulators of lymphoid development
      are a hallmark of B-progenitor acute lymphoblastic leukemia (B-ALL) and most
      commonly involve PAX5, encoding the DNA-binding transcription factor paired-box
      5. The majority of PAX5 alterations in ALL are heterozygous, and key PAX5 target
      genes are expressed in leukemic cells, suggesting that PAX5 may be a
      haploinsufficient tumor suppressor. To examine the role of PAX5 alterations in
      leukemogenesis, we performed mutagenesis screens of mice heterozygous for a loss
      of-function Pax5 allele. Both chemical and retroviral mutagenesis resulted in a
      significantly increased penetrance and reduced latency of leukemia, with a shift
      to B-lymphoid lineage. Genomic profiling identified a high frequency of secondary
      genomic mutations, deletions, and retroviral insertions targeting B-lymphoid
      development, including Pax5, and additional genes and pathways mutated in ALL,
      including tumor suppressors, Ras, and Janus kinase-signal transducer and
      activator of transcription signaling. These results show that in contrast to
      simple Pax5 haploinsufficiency, multiple sequential alterations targeting
      lymphoid development are central to leukemogenesis and contribute to the arrest
      in lymphoid maturation characteristic of ALL. This cross-species analysis also
      validates the importance of concomitant alterations of multiple cellular growth,
      signaling, and tumor suppression pathways in the pathogenesis of B-ALL. 

PMID- 25855604
TI  - MicroRNA-mediated mechanisms of the cellular stress response in atherosclerosis.
AB  - Atherosclerosis is characterised by the accumulation of lipid-laden macrophages
      in atherosclerotic lesions and occurs preferentially at arterial branching
      points, which are prone to inflammation during hyperlipidaemic stress. The
      increased susceptibility at branching sites of arteries is attributable to poor
      adaptation of arterial endothelial cells to disturbed blood flow. In the past 5
      years, several studies have provided mechanistic insights into the regulatory
      roles of microRNAs (miRNAs) in inflammatory activation, proliferation, and
      regeneration of endothelial cells during this maladaptive process. The
      intercellular transfer of vesicle-bound miRNAs contributes to arterial
      homeostasis, and the combinatorial effect of multiple miRNAs controls the
      unresolved inflammation orchestrated by macrophages in atherosclerotic lesions.
      In this Review, we highlight the miRNA-dependent regulation of the endothelial
      phenotype and the proliferative reserve that occurs in response to altered
      haemodynamic conditions as a prerequisite for atherogenic inflammation. In
      particular, we discuss the regulation of transcriptional modules by miRNAs and
      the protective role of complementary strand pairs, which encompasses remote miRNA
      signalling. In addition, we review the roles of miRNA tandems and describe the
      relevance of RNA target selection and competition to the behaviour of lesional
      macrophages. Elucidating miRNA-mediated regulatory mechanisms can aid the
      development of novel diagnostic and therapeutic strategies for atherosclerosis. 

PMID- 25855605
TI  - Epidemiology and pathophysiology of Takotsubo syndrome.
AB  - Takotsubo syndrome is an acute cardiac syndrome first described in 1990 and
      characterized by transient left ventricular dysfunction affecting more than one
      coronary artery territory, often in a circumferential apical, mid-ventricular, or
      basal distribution. Several pathophysiological explanations have been proposed
      for this syndrome and its intriguing appearance, and awareness is growing that
      these explanations might not be mutually exclusive. The reversible apical
      myocardial dysfunction observed might result from more than one
      pathophysiological phenomenon. The pathophysiology of Takotsubo syndrome is
      complex and integrates neuroendocrine physiology, potentially involving the
      cognitive centres of the brain, and including the hypothalamic-pituitary-adrenal
      axis. Cardiovascular responses are caused by the sudden sympathetic activation
      and surge in concentrations of circulating catecholamines. The multiple
      morphological changes seen in the myocardium match those seen after catecholamine
      induced cardiotoxicity. The acute prognosis and recurrence rate are now known to
      be worse than initially thought, and much still needs to be learned about the
      epidemiology and the underlying pathophysiology of this fascinating condition in
      order to improve diagnostic and treatment pathways. 

PMID- 25855607
TI  - Entomofauna of Ziban oasis, Biskra, Algeria.
AB  - An inventory was carried out at five stations in the oasis of Ziban, an oasis
      that is characterized by its high-quality dates, in order to study the
      relationships between the oasis ecosystem and its insect fauna. Specimens were
      sampled using pitfall traps containing ethylene glycol as a preservative. In
      total, 115 arthropod species were collected during 5 months of survey. These
      species belonged to 61 families, 17 orders, and 4 classes (12 orders from
      Insecta, 3 from Arachnida, 1 from Chilopoda, and 1 from Malocostraca). The most
      represented insect orders were Coleoptera (44.42%), Hymenoptera (20.86%), and
      Lepidoptera (7.87%). Represented in the collections were phytophagous,
      omnivorous, and predator/parasite species. Given the large number of species
      collected, and the largely unknown relationships existing between the various
      ecological groups, this study is a first step in the description of the oasis
      entomofauna. 

PMID- 25855606
TI  - Long noncoding RNAs in cardiac development and ageing.
AB  - A large part of the mammalian genome is transcribed into noncoding RNAs. Long
      noncoding RNAs (lncRNAs) have emerged as critical epigenetic regulators of gene
      expression. Distinct molecular mechanisms allow lncRNAs either to activate or to
      repress gene expression, thereby participating in the regulation of cellular and
      tissue function. LncRNAs, therefore, have important roles in healthy and diseased
      hearts, and might be targets for therapeutic intervention. In this Review, we
      summarize the current knowledge of the roles of lncRNAs in cardiac development
      and ageing. After describing the definition and classification of lncRNAs, we
      present an overview of the mechanisms by which lncRNAs regulate gene expression.
      We discuss the multiple roles of lncRNAs in the heart, and focus on the
      regulation of embryonic stem cell differentiation, cardiac cell fate and
      development, and cardiac ageing. We emphasize the importance of chromatin
      remodelling in this regulation. Finally, we discuss the therapeutic and biomarker
      potential of lncRNAs. 

PMID- 25855608
TI  - Lung sarcoidosis in children: update on disease expression and management.
AB  - BACKGROUND: Sarcoidosis is a rare lung disease in children. The aim of the
      present study was to provide update information on disease presentation and
      progression, patient management and prognosis factors in a cohort of children
      with lung sarcoidosis. METHODS: With the network of the French Reference Centre
      for Rare Lung Diseases (RespiRare), we collected information on a large cohort of
      paediatric thoracic sarcoidosis to provide information on disease presentation,
      management and outcome. RESULTS: Forty-one patients were included with a median
      age at diagnosis of 11.8  years (1.1-15.8), mostly from Afro-Caribbean and Sub
      Saharan origin. At diagnosis, 85% presented with a multi-organic disease, and no
      major differences were found regarding disease severity between the patients
      diagnosed before or after 10 years old. Corticosteroids were the most used
      treatment, with more intravenous pulses in the youngest patients. The 18-month
      outcome showed that patients diagnosed before 10 years old were more likely to
      recover (50% vs 29%), and presented fewer relapses (29% vs 58%). At 4-5 years of
      follow-up, relapses were mostly observed for patients diagnosed after 10 years
      old. DISCUSSION: In the included children, mostly of Afro-Caribbean and Sub
      Saharan origin, sarcoidosis seems severe, with multi-organic involvement and
      foreground general symptoms. Common prognosis factors are not suitable in
      paediatric patients, and a young age at diagnosis does not seem to be associated
      with a poorer prognosis. The study is ongoing to provide further information on
      the very-long-term follow-up of paediatric sarcoidosis.

PMID- 25855609
TI  - Sarcopenia definitions: where to draw the line? Response to Scarlata et al.

PMID- 25855610
TI  - An unusual cause of pulmonary embolism.

PMID- 25855611
TI  - Hypoxaemia, sport and polycythaemia: a case from Imperial College London.

PMID- 25855612
TI  - Identifying key hospital service quality factors in online health communities.
AB  - BACKGROUND: The volume of health-related user-created content, especially
      hospital-related questions and answers in online health communities, has rapidly
      increased. Patients and caregivers participate in online community activities to
      share their experiences, exchange information, and ask about recommended or
      discredited hospitals. However, there is little research on how to identify
      hospital service quality automatically from the online communities. In the past,
      in-depth analysis of hospitals has used random sampling surveys. However, such
      surveys are becoming impractical owing to the rapidly increasing volume of online
      data and the diverse analysis requirements of related stakeholders. OBJECTIVE: As
      a solution for utilizing large-scale health-related information, we propose a
      novel approach to identify hospital service quality factors and overtime trends
      automatically from online health communities, especially hospital-related
      questions and answers. METHODS: We defined social media-based key quality factors
      for hospitals. In addition, we developed text mining techniques to detect such
      factors that frequently occur in online health communities. After detecting these
      factors that represent qualitative aspects of hospitals, we applied a sentiment
      analysis to recognize the types of recommendations in messages posted within
      online health communities. Korea's two biggest online portals were used to test
      the effectiveness of detection of social media-based key quality factors for
      hospitals. RESULTS: To evaluate the proposed text mining techniques, we performed
      manual evaluations on the extraction and classification results, such as hospital
      name, service quality factors, and recommendation types using a random sample of
      messages (ie, 5.44% (9450/173,748) of the total messages). Service quality factor
      detection and hospital name extraction achieved average F1 scores of 91% and 78%,
      respectively. In terms of recommendation classification, performance (ie,
      precision) is 78% on average. Extraction and classification performance still has
      room for improvement, but the extraction results are applicable to more detailed
      analysis. Further analysis of the extracted information reveals that there are
      differences in the details of social media-based key quality factors for
      hospitals according to the regions in Korea, and the patterns of change seem to
      accurately reflect social events (eg, influenza epidemics). CONCLUSIONS: These
      findings could be used to provide timely information to caregivers, hospital
      officials, and medical officials for health care policies.

PMID- 25855614
TI  - Remediation of Cr(VI) contaminated soil using long-duration sodium thiosulfate
      supported by micro-nano networks.
AB  - In this work, a long-duration remediation agent (LRA) on hexavalent chromium
      (Cr(VI)) was developed using sodium thiosulfate (ST) supported by attapulgite
      (ATP) micro-nano networks induced through high-energy electron beam (HEEB)
      irradiation. The ATP networks could effectively reduce the leaching amount of
      Cr(VI) in soil. More importantly, the ATP networks could significantly control
      the leaching behavior of ST, and then prolong the duration and increase the
      reduction efficiency of ST on Cr(VI). As a result, LRA displayed high performance
      on controlling the migration of Cr(VI) and reducing Cr(VI) to Cr(III).
      Additionally, pot experiment indicated that LRA could effectively decrease the
      absorbed amount of Cr(VI) in corn, and reduce the inhibition effect of Cr(VI) on
      the growth of corn. Therefore, this work could provide a facile approach to
      remediate the Cr(VI)-contaminated soil and lower the harmful effect of Cr(VI) on
      crop. 

PMID- 25855613
TI  - Photocatalytic and photoelectrocatalytic degradation of the drug omeprazole on
      nanocrystalline titania films in alkaline media: Effect of applied electrical
      bias on degradation and transformation products.
AB  - Photocatalytic and photoelectrocatalytic degradation of the drug omeprazole has
      been studied in the presence of nanocrystalline titania films supported on glass
      slides or transparent FTO electrodes in alkaline environment. Its photocatalytic
      degradation rate was assessed by its UV absorbance and by HPLC, while its
      transformation products were analyzed by HR-LC-MS. Based on UV absorbance,
      omeprazole can be photocatalytically degraded at an average rate of 6.7*10(
      4)min(-1) under low intensity UVA irradiation of 1.5mWcm(-2) in the presence of a
      nanoparticulate titania film. This corresponds to degradation of 1.4mg of
      omeprazole per gram of the photocatalyst per liter of solution per hour. The
      photodegradation rate can be accelerated in a photoelectrochemical cell by
      applying a forward bias. In this case, the maximum rate reached under the present
      conditions was 11.6*10(-4)min(-1) by applying a forward bias of +0.6V vs.
      Ag/AgCl. Four major transformation products were successfully identified and
      their profiles were followed by HR-LC-MS. The major degradation path includes the
      scission of the sulfoxide bridge into the corresponding pyridine and
      benzimidazole ring derivates and this is accompanied by the release of sulfate
      anions in the reaction mixture. 

PMID- 25855615
TI  - Formation of iron (hydr)oxides during the abiotic oxidation of Fe(II) in the
      presence of arsenate.
AB  - Abiotic oxidation of Fe(II) is a common pathway in the formation of Fe
      (hydr)oxides under natural conditions, however, little is known regarding the
      presence of arsenate on this process. In hence, the effect of arsenate on the
      precipitation of Fe (hydr)oxides during the oxidation of Fe(II) is investigated.
      Formation of arsenic-containing Fe (hydr)oxides is constrained by pH and molar
      ratios of As:Fe during the oxidation Fe(II). At pH 6.0, arsenate inhibits the
      formation of lepidocrocite and goethite, while favors the formation of ferric
      arsenate with the increasing As:Fe ratio. At pH 7.0, arsenate promotes the
      formation of hollow-structured Fe (hydr)oxides containing arsenate, as the As:Fe
      ratio reaches 0.07. Arsenate effectively inhibits the formation of magnetite at
      pH 8.0 even at As:Fe ratio of 0.01, while favors the formation of lepidocrocite
      and green rust, which can be latterly degenerated and replaced by ferric arsenate
      with the increasing As:Fe ratio. This study indicates that arsenate and low pH
      value favor the slow growth of dense-structured Fe (hydr)oxides like spherical
      ferric arsenate. With the rapid oxidation rate of Fe(II) at high pH, ferric
      (hydr)oxides prefer to precipitate in the formation of loose-structured Fe
      (hydr)oxides like lepidocrocite and green rust. 

PMID- 25855616
TI  - Phosphogypsum as a soil fertilizer: Ecotoxicity of amended soil and elutriates to
      bacteria, invertebrates, algae and plants.
AB  - Phosphogypsum (PG) is a metal and radionuclide rich-waste produced by the
      phosphate ore industry, which has been used as soil fertilizer in many parts of
      the world for several decades. The positive effects of PG in ameliorating some
      soil properties and increasing crop yields are well documented. More recently
      concerns are emerging related with the increase of metal/radionuclide residues on
      soils and crops. However, few studies have focused on the impact of PG
      applications on soil biota, as well as the contribution to soils with elements in
      mobile fractions of PG which may affect freshwater species as well. In this
      context the main aim of this study was to assess the ecotoxicity of soils amended
      with different percentages of Tunisian phosphogypsum (0.0, 4.9, 7.4, 11.1, 16.6
      and 25%) and of elutriates obtained from PG - amended soil (0.0, 6.25, 12.5 and
      25% of PG) to a battery of terrestrial (Eisenia andrei, Enchytraeus crypticus,
      Folsomia candida, Hypoaspis aculeifer, Zea mays, Lactuca sativa) and aquatic
      species (Vibrio fischeri, Daphnia magna, Raphidocelis subcapitata, Lemna minor).
      Both for amended soils and elutriates, invertebrates (especially D. magna and E.
      andrei) were the most sensitive species, displaying acute (immobilization) and
      chronic (reproduction inhibition) effects, respectively. Despite the presence of
      some concerning metals in PG and elutriates (e.g., zinc and cadmium), the
      extremely high levels of calcium found in both test mediums, suggest that this
      element was the mainly responsible for the ecotoxicological effects observed.
      Terrestrial and aquatic plants were the most tolerant species, which is in line
      with studies supporting the application of PG to increase crop yields.
      Nevertheless, no stimulatory effects on growth were observed for any of the
      species tested despite the high levels of phosphorus added to soils by PG. Given
      the importance of soil invertebrates for several soil functions and services,
      this study gives rise to new serious concerns about the consequences of PG
      applications on agricultural soils. 

PMID- 25855618
TI  - Enrichment pathway analysis. The inflammatory genetic background in Bipolar
      Disorder.
AB  - INTRODUCTION: The pathophysiology of Bipolar Disorder (BD) is yet to be fully
      characterized. In the last years attention was focused on neurodevelopment or
      neurodegenerative events. In this context, hyper- and hypo- activation of
      inflammatory cascades may play a role in modulating the architecture and function
      of neuronal tissues. In the present paper we tested the enrichment of molecular
      pathways related to inflammatory cascades (IL-1, IL-2, IL-6, IL-8, TNF and INF)
      testing whether genes related to these systems hold more variations associated
      with the risk for BD than expected. METHODS: ~7000 bipolar patients and controls
      with genome-wide data available from NIMH dataset were analyzed. SNPs were
      imputed, checked for quality control, pruned and tested for association (0.01<p).
      Fisher test was conducted to test the enrichment within the pathways and the
      association was permutated (10(5) times) to limit false positive findings.
      RESULTS: As a result, IL-6, IL-8 and IFN related pathways held twice to thrice
      the number of expected variants associated with BD. These tests resisted the
      permutation analysis. LIMITATIONS: The restricted number of inflammatory
      components included in the analysis and the lack of functional consequences for
      some of the SNPs analyzed may be biased; however, these choices helped the
      authors to lighten the statistical computational load for the analyses and at the
      same time included possibly hidden SNPs in linkage disequilibrium with the
      analyzed variations. CONCLUSIONS: We bring evidence that the inflammatory
      cascades may be genetically varied in Bipolar patients. This genetic background
      may explain part of the pathophysiology of the disorder.

PMID- 25855619
TI  - The comparative impact of conservative treatment versus superficial venous
      surgery, for the treatment of venous leg ulcers: A systematic review of the
      impact on patients' quality of life.
AB  - OBJECTIVES: Leg ulcers are known to have a profound effect on patients' quality
      of life; however, the influence of different treatment approaches is unclear.
      This review aims to evaluate the comparative impact of conservative treatments
      and superficial venous surgery, for venous leg ulcers, on patients' Quality of
      Life. DATA SOURCES: Three electronic databases (PsycInfo, Medline and CINAHL),
      and reference lists of relevant articles, were searched. A total of 209 articles
      were initially identified, and 16 articles were included in the review. RESULTS:
      The results lend cautious support to the suggestion that all treatments have a
      positive effect on quality of life, regardless of type, whilst wound status also
      appears to be an important factor. CONCLUSIONS: Some evidence suggests that
      surgical treatment methods may lead to greater improvements in patients' quality
      of life than compression bandaging alone; however, future research may focus on
      the psychological mechanisms underlying such changes.

PMID- 25855617
TI  - Veteran exposure to suicide: Prevalence and correlates.
AB  - BACKGROUND: The aim of this study was to determine rates and consequences of
      suicide exposure in a veteran population and variables related to psychiatric
      morbidity. METHODS: 931 veterans from a random digit dial survey conducted July
      2012-June 2013 in the Commonwealth of Kentucky was utilized to examine
      associations between suicide exposure and depression and anxiety. For those with
      lifetime suicide exposure, perceptions of closeness to the decedent and
      additional traumatic death exposure were also examined. RESULTS: Almost half of
      veterans (47.1%, n=434) reported lifetime exposure to suicide. Suicide-exposed
      individuals were almost twice as likely to have diagnosable depression (OR=1.92,
      CI=1.31-2.8) and more than twice as likely to have diagnosable anxiety (OR=2.37,
      CI=1.55-3.61). Suicide-exposed were also more likely than non-exposed to report
      suicide ideation (9.9% vs. 4.3%). Perceived closeness to decedent increased the
      odds of depression (OR=1.38, CI=1.12-1.69), anxiety (OR=1.51, CI=1.21-1.89) and
      PTSD (OR=1.65, CI=1.27-2.16) and more than doubled the odds of Prolonged Grief
      (OR=2.47, CI=1.60-3.83). A model examined time sequence of suicide and traumatic
      death exposure. Experiencing a suicide exposure first and subsequent traumatic
      death exposure in their military career almost quadrupled the odds of suicide
      ideation (OR=3.56, p=.01, CI=1.34-9.46). LIMITATIONS: Major study limitations
      include use of only one US state and random digit dial response rate.
      CONCLUSIONS: Suicide exposure confers psychiatric risks in veterans. Perceptions
      of closeness to decedents, which may extend beyond familial lines, may heighten
      these risks in the suicide exposed. Multiple exposures to suicide and traumatic
      death may lead to significant suicide risk.

PMID- 25855620
TI  - Early trials of Ebola vaccine show immune response.

PMID- 25855621
TI  - Efficacy of erlotinib in previously treated patients with advanced non-small cell
      lung cancer: analysis of the Chinese subpopulation in the TRUST study.
AB  - OBJECTIVE: This study is to analyze the data of Chinese subpopulation in the
      Tarceva Lung Cancer Survival Treatment Study (TRUST-China) which was a global
      Phase IV study designed to provide erlotinib to previously treated patients with
      Stage IIIB/IV non-small cell lung cancer. METHODS: Patients with pathologically
      confirmed, unresectable Stage IIIB/IV non-small cell lung cancer who were
      previously failed on or unsuitable for chemotherapy or radiotherapy were given
      erlotinib (150 mg/day, oral) until disease progression, intolerable toxicity or
      death. Efficacy and toxicity of the agent were evaluated. RESULTS: In total, 519
      patients Chinese patients were analyzed. The TRUST-China had similar baseline
      characteristics to TRUST-Global except the greater percentage of adenocarcinoma
      and non-smoker cases. The response rate and disease control rate were 24.7 and
      75.3%, respectively. Median progression-free survival and overall survival were
      6.4 and 15.4 months in the general Chinese population in the TRUST, and 10.2 and
      18.9 months in non-smokers with adenocarcinoma (n = 254). Median progression-free
      survival and overall survival were significantly longer in non-smokers with
      adenocarcinoma than those in other groups (P <= 0.0001 and P <= 0.0001,
      respectively). Eastern Cooperative Oncology Group Performance Status (>= 2 vs. <=
      1, hazard ratio = 1.746, P < 0.0001) and histology (squamous cell carcinoma vs.
      adenocarcinoma, hazard ratio = 1.595, P = 0.0008) were independent risk factors
      that affected survival according to Cox regression multivariate analysis.
      CONCLUSIONS: We confirmed the efficacy and safety of erlotinib in Chinese
      patients. Non-smoking patients with adenocarcinoma histology had the best
      clinical benefits. (NCT00949910).

PMID- 25855622
TI  - Hannaella phyllophila sp. nov., a basidiomycetous yeast species associated with
      plants in Thailand and Taiwan.
AB  - Five strains representing one novel anamorphic yeast species were isolated from
      plant leaves collected in Thailand (strains DMKU-SP186(T), ST-111 and ST-201) and
      Taiwan (strains FN20L02 and SM13L16). On the basis of morphological, biochemical,
      physiological and chemotaxonomic characteristics and sequence analysis of the
      D1/D2 region of the large subunit (LSU) rRNA gene and the internal transcribed
      spacer (ITS) region, they were assigned to a single novel species of the genus
      Hannaella. The sequences of the D1/D2 regions of the LSU rRNA genes of four of
      the strains (DMKU-SP186(T), ST-111, FN20L02 and SM13L16) were identical, while
      differing from strain ST-201 by 2 substitutions and 2 gaps. The nucleotide
      sequence of the ITS regions of the five strains differed from each other by
      between 0 and 3 nucleotide substitutions. The novel species was most closely
      related to Hannaella luteola, but showed 1.0-1.3% nucleotide substitutions
      (between 6 substitutions out of 568-606 nt and 8 substitutions, and 2 gaps out of
      597 nt) in the D1/D2 region of the LSU rRNA gene and 1.4-2.0% nucleotide
      substitutions (6-9 substitutions out of 435 nt) in the ITS region. Ballistospores
      were produced by three of the strains on cornmeal agar at 15 and 20  degrees C
      after 4 weeks, while H. luteola did not produce ballistospores. The name
      Hannaella phyllophila sp. nov. is proposed. The type strain is DMKU-SP186(T) ( =
      BCC 69500(T) = NBRC 110428(T) = CBS 13921(T)).

PMID- 25855623
TI  - Methanoculleus sediminis sp. nov., a methanogen from sediments near a submarine
      mud volcano.
AB  - A mesophilic, hydrogenotrophic methanogen, strain S3Fa(T), was isolated from
      sediments collected by Ocean Researcher I cruise ORI-934 in 2010 near the
      submarine mud volcano MV4 located at the upper slope of south-west Taiwan. The
      methanogenic substrates utilized by strain S3Fa(T) were formate and H2/CO2 but
      not acetate, secondary alcohols, methylamines, methanol or ethanol. Cells of
      strain S3Fa(T) were non-motile, irregular cocci, 0.5-1.0 MUm in diameter. The
      surface-layer protein showed an Mr of 128,000.The optimum growth conditions were
      37  degrees C, pH 7.1 and 0.17 M NaCl. The DNA G+C content of the genome of
      strain S3Fa(T) was 62.3 mol%. Phylogenetic analysis revealed that strain S3Fa(T)
      was most closely related to Methanoculleus marisnigri JR1(T) (99.3% 16S rRNA gene
      sequence similarity). Genome relatedness between strain S3Fa(T) and
      Methanoculleus marisnigri JR1(T) was computed using both genome-to-genome
      distance analysis (GGDA) and average nucleotide identity (ANI) with values of
      46.3-55.5% and 93.08%, respectively. Based on morphological, phenotypic,
      phylogenetic and genomic relatedness data, it is evident that strain S3Fa(T)
      represents a novel species of the genus Methanoculleus, for which the name
      Methanoculleus sediminis sp. nov. is proposed. The type strain is S3Fa(T) ( =
      BCRC AR10044(T) = DSM 29354(T)).

PMID- 25855624
TI  - Olympics and Paralympics 2012 mass gathering in London: time-series analysis
      shows no increase in attendances at sexual health clinics.
AB  - OBJECTIVE: To determine whether the 2012 Olympic and Paralympic Games were
      associated with a change in the number of patients attending or diagnosed with a
      new sexually transmitted infection (STI) at sexual health clinics in London and
      Weymouth. METHODS: We undertook an interrupted time-series analysis of
      surveillance data from the Genitourinary Medicine Clinic Activity Dataset
      (GUMCAD) collected at 33 genitourinary medicine (GUM) clinics in London and
      Weymouth (where Games events were concentrated) between 2009 and 2012. Mixed
      effects linear regression models of weekly attendance and diagnoses,
      incorporating temporal trends, bank holidays, categorical month and clinic
      closures, were used to test for the effect of the 'Olympic-Paralympic' period. We
      subdivided the 9-week 'Olympic-Paralympic' period (16 July 2012 to 17 September
      2012) into five periods, including three Olympic weeks, two Paralympic weeks, pre
      , post- and inter-Games weeks. We also compared characteristics of patients
      attending during the Olympic-Paralympic period and those attending during the
      same period in 2011. RESULTS: During the 3 weeks of the Olympics, there was a
      significant reduction in the number of new episode attendances (2020 fewer, 5.6%
      reduction (95% CI -8.2 to -2.9)) and the number of patients diagnosed with an STI
      (267 fewer, 4.8% reduction (95% CI -8.6 to -0.9)) compared to expected. There
      were no important differences in the profile of patients attending during the
      2012 Olympic-Paralympic period and those attending during the same period in
      2011. CONCLUSIONS: We conclude that a 'business-as-usual' approach to managing
      local sexual health clinics during the 2012 Olympic and Paralympics would have
      been appropriate.

PMID- 25855625
TI  - Point-of-care management of urogenital Chlamydia trachomatis via Gram-stained
      smear analysis in male high-risk patients. Diagnostic accuracy and cost
      effectiveness before and after changing the screening indication at the STI
      Clinic in Amsterdam.
AB  - OBJECTIVES: To measure the effect of changing the point-of-care (POC) testing
      algorithm of urogenital chlamydia for all male high-risk patients to those with
      only symptoms with respect to: diagnostic accuracy, loss to follow-up, correctly
      managed consultations and costs. METHODS: Retrospective comparison of the
      diagnostic accuracy and cost-effectiveness of Gram-stained urethral smear
      analysis for the POC management of urogenital Chlamydia trachomatis infections.
      Between 2008 and 2009 Gram-stained urethral smear analysis was offered to all men
      irrespective of symptoms; between 2010 and 2011 only to those with symptoms. The
      Aptima CT assay was the reference diagnostic test. RESULTS: The number of
      examined Gram-stained smears in the two periods was respectively 7185 (2008-2009
      period) and 18,852 (2010-2011 period). The sensitivity of the Gram stain analysis
      was respectively 83.8% (95% CI 81.2% to 86.1%) and 91.0% (95% CI 89.5% to 92.3%)
      (p<0.001). The specificity was respectively 74.1% (95% CI 73.0% to 75.2%) and
      53.1% (95% CI 51.8% to 54.4%) (p<0.001). The positive predictive value was low in
      both periods, respectively 31.7% (95% CI 29.8% to 33.6%) and 35.6% (95% CI 34.1%
      to 37.1%) (p=0.002), whereas the negative predictive value was high, respectively
      97.0% (95% CI 96.4% to 97.4%) and 95.4% (95% CI 94.6% to 96.1%) (p=0.002). The
      loss to follow-up rate between 2008-2009 and 2010-2011 was, respectively, 1.8%
      (95% CI 1.0% to 2.9%) vs 2.3% (95% CI 1.7% to 3.0%) (p=0.36). There was a small
      difference in overtreatment, 68.0% (95% CI 66.0% to 69.8%) vs 64.1% (95% CI 62.6%
      to 65.5%) (p=0.001). The cost per correctly managed consultation was 14.3% lower
      in the 2010-2011 period (?94.31 vs ?80.82). The percentage of delayed treated
      infections was significantly lower in the 2008-2009 period (10.5%) compared with
      the 2010-2011 period (22.8%) (p<0.001). CONCLUSIONS: With a high sensitivity in
      male high-risk patients, the Gram-stained urethral smear is a useful POC test to
      detect urogenital C. trachomatis. When offered only to men with urogenital
      symptoms the specificity decreases but the cost per correctly managed
      consultation is reduced with 14.3% without a significant difference in loss to
      follow-up but with a significantly higher rate of delayed treatment.

PMID- 25855627
TI  - Adult body size and physical activity in relation to risk of breast cancer
      according to tumor androgen receptor status.
AB  - BACKGROUND: Obesity and physical activity have been hypothesized to affect breast
      cancer risk partly via the androgen signaling pathway. We conducted the first
      study to evaluate these associations by tumor androgen receptor (AR) status.
      METHODS: Height, weight, and physical activity were assessed using questionnaires
      in the Nurses' Health Study. AR, estrogen receptor (ER), and progesterone
      receptor (PR) status were determined using immunohistochemistry on tumor tissue
      and medical/pathology reports. RESULTS: A total of 1,701 AR(+) and 497 AR(-)
      cases were documented during 26 years of follow-up of 103,577 women. After
      adjusting for ER/PR status and other risk factors, the relative risks (RR) and
      95% confidence intervals (95% CI) for every 5 kg/m(2) increase in body mass index
      (BMI) were 1.07 (1.01-1.13) for AR(+) and 1.16 (1.05-1.29) for AR(-) tumors (P
      heterogeneity = 0.17). The RRs (95% CIs) per 5 hours of brisk walking/week were
      0.87 (0.73-1.04) for AR(+) and 0.67 (0.45-0.99) for AR(-) tumors (P-heterogeneity
      = 0.22). Further, BMI, but not physical activity, associations differed
      significantly across ER/PR/AR subtypes (P-heterogeneity = 0.04 and 0.63,
      respectively). The RRs (95% CIs) for 5 kg/m(2) increase in BMI were 1.23 (1.04
      1.45) for ER(+)PR(+)AR(-), 1.19 (1.01-1.39) for ER(-)PR(-)AR(-), 1.15 (1.08-1.23)
      for ER(+)PR(+)AR(+), and 0.88 (0.75-1.03) for ER(+)PR(-)AR(+) tumors.
      CONCLUSIONS: Higher BMI was associated with an increased risk of both AR(+) and
      AR(-) breast tumors in postmenopausal women, whereas physical activity, including
      brisk walking, was associated with a reduced risk of both subtypes. In addition,
      a significant positive association was observed between higher BMI and ER(-)PR(
      )AR(-) tumors. IMPACT: The similar associations observed by AR status suggest
      that mechanisms other than androgen signaling underlie these two breast cancer
      risk factors.

PMID- 25855626
TI  - Inflammatory Markers and Risk of Epithelial Ovarian Cancer by Tumor Subtypes: The
      EPIC Cohort.
AB  - BACKGROUND: Evidence suggests an etiologic role for inflammation in ovarian
      carcinogenesis and heterogeneity between tumor subtypes and anthropometric
      indices. Prospective studies on circulating inflammatory markers and epithelial
      invasive ovarian cancer (EOC) have predominantly investigated overall risk; data
      characterizing risk by tumor characteristics (histology, grade, stage, dualistic
      model of ovarian carcinogenesis) and anthropometric indices are sparse. METHODS:
      We conducted a nested case-control study in the European Prospective
      Investigation into Cancer and Nutrition (EPIC) cohort to evaluate C-reactive
      protein (CRP), IL6, and EOC risk by tumor characteristics. A total of 754
      eligible EOC cases were identified; two controls (n = 1,497) were matched per
      case. We used multivariable conditional logistic regression to assess
      associations. RESULTS: CRP and IL6 were not associated with overall EOC risk.
      However, consistent with prior research, CRP >10 versus CRP <=1 mg/L was
      associated with higher overall EOC risk [OR, 1.67 (1.03-2.70)]. We did not
      observe significant associations or heterogeneity in analyses by tumor
      characteristics. In analyses stratified by waist circumference, inflammatory
      markers were associated with higher risk among women with higher waist
      circumference; no association was observed for women with normal waist
      circumference [e.g., IL6: waist <=80: ORlog2, 0.97 (0.81-1.16); waist >88:
      ORlog2, 1.78 (1.28-2.48), Pheterogeneity <= 0.01]. CONCLUSIONS: Our data suggest
      that high CRP is associated with increased risk of overall EOC, and that IL6 and
      CRP may be associated with EOC risk among women with higher adiposity. IMPACT:
      Our data add to global evidence that ovarian carcinogenesis may be promoted by an
      inflammatory milieu.

PMID- 25855629
TI  - IMAGING IN ENDOCRINOLOGY: The use of functional MRI to study the endocrinology of
      appetite.
AB  - In the present review article, we summarise current thinking about the
      neuroendocrinology of appetite and feeding behaviour. We discuss how the
      homeostatic control of energy balance, wherein the hypothalamus orchestrates food
      intake and energy expenditure in response to peripheral signals about nutritional
      status, can be easily overridden by the powerful reward value of food. We focus
      on how functional magnetic resonance imaging has shed light on our understanding
      of the way hormones can interact with the brain to modulate appetite. 

PMID- 25855628
TI  - Prospective analysis of adrenal function in patients with acute exacerbations of
      COPD: the Reduction in the Use of Corticosteroids in Exacerbated COPD (REDUCE)
      trial.
AB  - OBJECTIVE: To analyze prospectively the hypothalamic-pituitary-adrenal (HPA) axis
      and clinical outcome in patients treated with prednisone for exacerbated chronic
      obstructive pulmonary disease (COPD). DESIGN: Prospective observational study.
      SUBJECTS AND METHODS: Patients presenting to the emergency department were
      randomized to receive 40 mg prednisone daily for 5 or 14 days in a placebo
      controlled manner. The HPA axis was longitudinally assessed with the 1 MUg
      corticotropin test and a clinical hypocortisolism score at baseline, on day 6
      before blinded treatment, at hospital discharge, and for up to 180 days of follow
      up. Prednisone was stopped abruptly, irrespective of the test results. Patients
      discharged with pathological test results received instructions about emergency
      hydrocortisone treatment. RESULTS: A total of 311 patients were included in the
      analysis. Mean basal and stimulated serum total cortisol levels were highest on
      admission (496+/-398 and 816+/-413 nmol/l respectively) and lowest on day 6
      (235+/-174 and 453+/-178 nmol/l respectively). Pathological stimulation tests
      were found in 63, 38, 9, 3, and 2% of patients on day 6, at discharge, and on
      days 30, 90, and 180 respectively, without significant difference between
      treatment groups. Clinical indicators of hypocortisolism did not correlate with
      stimulation test results, but cortisol levels were inversely associated with re
      exacerbation risk. There were no hospitalizations or deaths as a result of
      adrenal crisis. CONCLUSION: Dynamic changes in the HPA axis occur during and
      after the treatment of acute exacerbations of COPD. In hypocortisolemic patients
      who were provided with instructions about stress prophylaxis, the abrupt
      termination of prednisone appeared safe.

PMID- 25855630
TI  - US foundation, university, and drug company are sued for alleged role in
      Guatemala study.

PMID- 25855631
TI  - The adolescent's experience when a parent has advanced cancer: A qualitative
      inquiry.
AB  - BACKGROUND: Parental cancer is a stressful experience for young people,
      constituting a potential threat to physical and mental health and normative
      development. Currently, there is insufficient information describing the sources
      and nature of this distress during advanced parental cancer, especially
      concerning families with adolescent children. AIM: To address the significant gap
      in the literature by providing the adolescent's perspective on the impact of
      their parent's advanced cancer on their lives. DESIGN: This qualitative study
      involved single-occasion, semi-structured elicitation interviews with adolescents
      whose parents were diagnosed with advanced stage cancer. SETTING/PARTICIPANTS:
      The study sample consisted of seven adolescents from six families, five females
      and two males ranging in age from 11 to 15 years (mean = 13.6 years, standard
      deviation = 1.4 years). The ill parents consisted of four females and two males
      diagnosed with Stage IV cancer. RESULTS: The core construct that organized study
      results was Weaving a Normal Life with Cancer which involved five major domains:
      feeling the weight of the world on my shoulders; cancer changes everything;
      confronting or getting away from the cancer; talking about it; and cancer was a
      positive for me ... it taught me. CONCLUSION: Study findings shed light on how
      adolescents self-manage their parent's advanced cancer and work to delimit the
      illness even as they are aware of its constant presence. Future research and
      intervention studies are needed to support and add to the adolescents' self
      management strategies to weave a normal life for themselves while in the throes
      of the cancer's uncertainty and challenges with family communication.

PMID- 25855632
TI  - Delirium as letting go: An ethnographic analysis of hospice care and family moral
      experience.
AB  - BACKGROUND: Delirium is extremely common in dying patients and appears to be a
      major threat to the family's moral experience of a good death in end-of-life
      care. AIM: To illustrate one of the ways in which hospice caregivers
      conceptualize end-of-life delirium and the significance of this conceptualization
      for the relationships that they form with patients' families in the hospice
      setting. DESIGN: Ethnography. SETTING/PARTICIPANTS: Ethnographic fieldwork was
      conducted at a nine-bed, freestanding residential hospice, located in a suburban
      community of Eastern Canada. Data collection methods included 15 months of
      participant observation, 28 semi-structured audio-recorded interviews with
      hospice caregivers, and document analysis. RESULTS: Hospice caregivers draw on a
      culturally established framework of normal dying to help families come to terms
      with clinical end-of-life phenomena, including delirium. By offering explanations
      about delirium as a natural feature of the dying process, hospice caregivers
      strive to protect for families the integrity of the good death ideal. CONCLUSION:
      Within hospice culture, there is usefulness to deemphasizing delirium as a
      pathological neuropsychiatric complication, in favor of acknowledging delirious
      changes as signs of normal dying. This has implications for how we understand the
      role of nurses and other caregivers with respect to delirium assessment and care,
      which to date has focused largely on practices of screening and management.

PMID- 25855633
TI  - Novel function of vitamin E in regulation of zebrafish (Danio rerio) brain
      lysophospholipids discovered using lipidomics.
AB  - We hypothesized that brains from vitamin E-deficient (E-) zebrafish (Danio rerio)
      would undergo increased lipid peroxidation because they contain highly
      polyunsaturated fatty acids, thus susceptible lipids could be identified. Brains
      from zebrafish fed for 9 months defined diets without (E-) or with (E+) added
      vitamin E (500 mg RRR-alpha-tocopheryl acetate per kilogram diet) were studied.
      Using an untargeted approach, 1-hexadecanoyl-2-docosahexaenoyl-sn-glycero-3
      phosphocholine [DHA-PC 38:6, PC 16:0/22:6]was the lipid that showed the most
      significant and greatest fold-differences between groups. DHA-PC concentrations
      were approximately 1/3 lower in E- (4.3 +/- 0.6 mg/g) compared with E+ brains
      (6.5 +/- 0.9 mg/g, mean +/- SEM, n = 10 per group, P = 0.04). Using lipidomics,
      155 lipids in brain extracts were identified. Only four phospholipids (PLs) were
      different (P < 0.05) between groups; they were lower in E- brains and contained
      DHA with DHA-PC 38:6 at the highest abundances. Moreover, hydroxy-DHA-PC 38:6 was
      increased in E- brains (P = 0.0341) supporting the hypothesis of DHA
      peroxidation. More striking was the depletion in E- brains of nearly 60% of 19
      different lysophospholipids (lysoPLs) (combined P = 0.0003), which are critical
      for membrane PL remodeling. Thus, E- brains contained fewer DHA-PLs, more hydroxy
      DHA-PCs, and fewer lysoPLs, suggesting that lipid peroxidation depletes membrane
      DHA-PC and homeostatic mechanisms to repair the damage resulting in lysoPL
      depletion. 

PMID- 25855634
TI  - Structural characterization of toxic oligomers that are kinetically trapped
      during alpha-synuclein fibril formation.
AB  - We describe the isolation and detailed structural characterization of stable
      toxic oligomers of alpha-synuclein that have accumulated during the process of
      amyloid formation. Our approach has allowed us to identify distinct subgroups of
      oligomers and to probe their molecular architectures by using cryo-electron
      microscopy (cryoEM) image reconstruction techniques. Although the oligomers exist
      in a range of sizes, with different extents and nature of beta-sheet content and
      exposed hydrophobicity, they all possess a hollow cylindrical architecture with
      similarities to certain types of amyloid fibril, suggesting that the accumulation
      of at least some forms of amyloid oligomers is likely to be a consequence of very
      slow rates of rearrangement of their beta-sheet structures. Our findings reveal
      the inherent multiplicity of the process of protein misfolding and the key role
      the beta-sheet geometry acquired in the early stages of the self-assembly process
      plays in dictating the kinetic stability and the pathological nature of
      individual oligomeric species. 

PMID- 25855635
TI  - Molecular determinants of the interactions between proteins and ssDNA.
AB  - ssDNA binding proteins (SSBs) protect ssDNA from chemical and enzymatic assault
      that can derail DNA processing machinery. Complexes between SSBs and ssDNA are
      often highly stable, but predicting their structures is challenging, mostly
      because of the inherent flexibility of ssDNA and the geometric and energetic
      complexity of the interfaces that it forms. Here, we report a newly developed
      coarse-grained model to predict the structure of SSB-ssDNA complexes. The model
      is successfully applied to predict the binding modes of six SSBs with ssDNA
      strands of lengths of 6-65 nt. In addition to charge-charge interactions (which
      are often central to governing protein interactions with nucleic acids by means
      of electrostatic complementarity), an essential energetic term to predict SSB
      ssDNA complexes is the interactions between aromatic residues and DNA bases. For
      some systems, flexibility is required from not only the ssDNA but also, the SSB
      to allow it to undergo conformational changes and the penetration of the ssDNA
      into its binding pocket. The association mechanisms can be quite varied, and in
      several cases, they involve the ssDNA sliding along the protein surface. The
      binding mechanism suggests that coarse-grained models are appropriate to study
      the motion of SSBs along ssDNA, which is expected to be central to the function
      carried out by the SSBs. 

PMID- 25855636
TI  - Hydrophilic microenvironment required for the channel-independent insertase
      function of YidC protein.
AB  - The recently solved crystal structure of YidC protein suggests that it mediates
      membrane protein insertion by means of an intramembrane cavity rather than a
      transmembrane (TM) pore. This concept of protein translocation prompted us to
      characterize the native, membrane-integrated state of YidC with respect to the
      hydropathic nature of its TM region. Here, we show that the cavity-forming region
      of the stage III sporulation protein J (SpoIIIJ), a YidC homolog, is indeed open
      to the aqueous milieu of the Bacillus subtilis cells and that the overall
      hydrophilicity of the cavity, along with the presence of an Arg residue on
      several alternative sites of the cavity surface, is functionally important. We
      propose that YidC functions as a proteinaceous amphiphile that interacts with
      newly synthesized membrane proteins and reduces energetic costs of their membrane
      traversal. 

PMID- 25855638
TI  - Artemisinin-based combination therapy in the treatment of uncomplicated malaria:
      review of recent regulatory experience at the European Medicines Agency.
AB  - Malaria remains a major public health challenge with almost half of the world's
      population exposed to the risk of contracting the illness. Prompt, effective and
      well tolerated treatment remains one of the cornerstones in the disease
      management, with artemisinin-based combination therapy the recommended option for
      non-severe malaria in endemic areas with predominant Plasmodium falciparum
      infections.Recent experience has been obtained at the European Medicines Agency
      with regulatory approval of two such antimalarial fixed combination products. For
      these cases, two different regulatory pathways were applied. As such, the present
      contribution describes this experience, emphasising main differences and
      applicability offered by these regulatory choices.

PMID- 25855637
TI  - Cadherin flexibility provides a key difference between desmosomes and adherens
      junctions.
AB  - Desmosomes and adherens junctions are intercellular adhesive structures essential
      for the development and integrity of vertebrate tissue, including the epidermis
      and heart. Their cell adhesion molecules are cadherins: type 1 cadherins in
      adherens junctions and desmosomal cadherins in desmosomes. A fundamental
      difference is that desmosomes have a highly ordered structure in their
      extracellular region and exhibit calcium-independent hyperadhesion, whereas
      adherens junctions appear to lack such ordered arrays, and their adhesion is
      always calcium-dependent. We present here the structure of the entire ectodomain
      of desmosomal cadherin desmoglein 2 (Dsg2), using a combination of small-angle X
      ray scattering, electron microscopy, and solution-based biophysical techniques.
      This structure reveals that the ectodomain of Dsg2 is flexible even in the
      calcium-bound state and, on average, is shorter than the type 1 cadherin crystal
      structures. The Dsg2 structure has an excellent fit with the electron tomography
      reconstructions of human desmosomes. This fit suggests an arrangement in which
      desmosomal cadherins form trans interactions but are too far apart to interact in
      cis, in agreement with previously reported observations. Cadherin flexibility may
      be key to explaining the plasticity of desmosomes that maintain tissue integrity
      in their hyperadhesive form, but can adopt a weaker, calcium-dependent adhesion
      during wound healing and early development. 

PMID- 25855639
TI  - CALHM1 Deletion in Mice Affects Glossopharyngeal Taste Responses, Food Intake,
      Body Weight, and Life Span.
AB  - Stimulation of Type II taste receptor cells (TRCs) with T1R taste receptors
      causes sweet or umami taste, whereas T2Rs elicit bitter taste. Type II TRCs
      contain the calcium channel, calcium homeostasis modulator protein 1 (CALHM1),
      which releases adenosine triphosphate (ATP) transmitter to taste fibers. We have
      previously demonstrated with chorda tympani nerve recordings and two-bottle
      preference (TBP) tests that mice with genetically deleted Calhm1 (knockout [KO])
      have severely impaired perception of sweet, bitter, and umami compounds, whereas
      their sour and salty tasting ability is unaltered. Here, we present data from KO
      mice of effects on glossopharyngeal (NG) nerve responses, TBP, food intake, body
      weight, and life span. KO mice have no NG response to sweet and a suppressed
      response to bitter compared with control (wild-type [WT]) mice. KO mice showed
      some NG response to umami, suggesting that umami taste involves both CALHM1- and
      non-CALHM1-modulated signals. NG responses to sour and salty were not
      significantly different between KO and WT mice. Behavioral data conformed in
      general with the NG data. Adult KO mice consumed less food, weighed significantly
      less, and lived almost a year longer than WT mice. Taken together, these data
      demonstrate that sweet taste majorly influences food intake, body weight, and
      life span. 

PMID- 25855640
TI  - Differential responsiveness to cigarette price by education and income among
      adult urban Chinese smokers: findings from the ITC China Survey.
AB  - BACKGROUND: Few studies have examined the impact of tobacco tax and price
      policies in China. In addition, very little is known about the differential
      responses to tax and price increases based on socioeconomic status in China.
      OBJECTIVE: To estimate the conditional cigarette consumption price elasticity
      among adult urban smokers in China and to examine the differential responses to
      cigarette price increases among groups with different income and/or educational
      levels. METHODS: Multivariate analyses employing the general estimating equations
      method were conducted using the first three waves of the International Tobacco
      Control (ITC) China Survey. Analyses based on subsample by education and income
      were conducted. FINDINGS: Conditional cigarette demand price elasticity ranges
      from -0.12 to -0.14. No differential responses to cigarette price increase were
      found across education levels. The price elasticity estimates do not differ
      between high-income smokers and medium-income smokers. Cigarette consumption
      among low-income smokers did not decrease after a price increase, at least among
      those who continued to smoke. CONCLUSIONS: Relative to other low-income and
      middle-income countries, cigarette consumption among Chinese adult smokers is not
      very sensitive to changes in cigarette prices. The total impact of cigarette
      price increase would be larger if its impact on smoking initiation and cessation,
      as well as the price-reducing behaviours such as brand switching and trading
      down, were taken into account.

PMID- 25855641
TI  - The association between tax structure and cigarette price variability: findings
      from the ITC Project.
AB  - BACKGROUND: Recent studies have shown that more opportunities exist for tax
      avoidance when cigarette excise tax structure departs from a uniform specific
      structure. However, the association between tax structure and cigarette price
      variability has not been thoroughly studied in the existing literature.
      OBJECTIVE: To examine how cigarette tax structure is associated with price
      variability. The variability of self-reported prices is measured using the ratios
      of differences between higher and lower prices to the median price such as the
      IQR-to-median ratio. METHODS: We used survey data taken from the International
      Tobacco Control Policy Evaluation (ITC) Project in 17 countries to conduct the
      analysis. Cigarette prices were derived using individual purchase information and
      aggregated to price variability measures for each surveyed country and wave. The
      effect of tax structures on price variability was estimated using Generalised
      Estimating Equations after adjusting for year and country attributes. FINDINGS:
      Our study provides empirical evidence of a relationship between tax structure and
      cigarette price variability. We find that, compared to the specific uniform tax
      structure, mixed uniform and tiered (specific, ad valorem or mixed) structures
      are associated with greater price variability (p<=0.01). Moreover, while a
      greater share of the specific component in total excise taxes is associated with
      lower price variability (p<=0.05), a tiered tax structure is associated with
      greater price variability (p<=0.01). The results suggest that a uniform and
      specific tax structure is the most effective tax structure for reducing tobacco
      consumption and prevalence by limiting price variability and decreasing
      opportunities for tax avoidance.

PMID- 25855642
TI  - The heterogeneous effects of cigarette prices on brand choice in China:
      implications for tobacco control policy.
AB  - BACKGROUND: China has long kept its tobacco taxes below international standards.
      The Chinese government has cited two rationales against raising tobacco tax,
      namely, the unfair burden it places on low-income smokers and the ability of
      consumers to switch to cheaper brands. OBJECTIVE: This study examines how
      different socioeconomic subgroups of Chinese smokers switch brands in response to
      cigarette price changes. METHODS: We model smokers' choice of cigarette tier as a
      function of tier-specific prices. We examine heterogeneous responses to prices by
      estimating mixed logit models for different income and education subgroups that
      allow for random variation in smokers' preferences. We use data from three waves
      of the longitudinal International Tobacco Control China Survey, collected in six
      large Chinese cities between 2006 and 2009. FINDINGS: Low-income and less
      educated smokers are considerably more likely to switch tiers (including both up
      trading and down-trading) than are their high-socioeconomic status (SES)
      counterparts. For those in the second-to-lowest tier, a Y1 ($0.16, or roughly
      25%) rise in prices increases the likelihood of switching tiers by 5.6% points
      for low-income smokers and 7.2% points for less educated smokers, compared to
      1.6% and 3.0% points for the corresponding high-SES groups. Low-income and less
      educated groups are also more likely to trade down compared to their high-SES
      counterparts. CONCLUSIONS: Only a small percentage of low-income and less
      educated Chinese smokers switched to cheaper brands in response to price
      increases. Hence, the concern of the Chinese government that a cigarette tax
      increase will lead to large-scale brand switching is not supported by this study.

PMID- 25855644
TI  - The NHS in Wales: faring worse than the rest of the UK?

PMID- 25855643
TI  - Stem cell and progenitor fate in the mammalian intestine: Notch and lateral
      inhibition in homeostasis and disease.
AB  - The control of cell fate decisions is vital to build functional organs and
      maintain normal tissue homeostasis, and many pathways and processes cooperate to
      direct cells to an appropriate final identity. Because of its continuously
      renewing state and its carefully organised hierarchy, the mammalian intestine has
      become a powerful model to dissect these pathways in health and disease. One of
      the signalling pathways that is key to maintaining the balance between
      proliferation and differentiation in the intestinal epithelium is the Notch
      pathway, most famous for specifying distinct cell fates in adjacent cells via the
      evolutionarily conserved process of lateral inhibition. Here, we will review
      recent discoveries that advance our understanding of how cell fate in the
      mammalian intestine is decided by Notch and lateral inhibition, focusing on the
      molecular determinants that regulate protein turnover, transcriptional control
      and epigenetic regulation. 

PMID- 25855645
TI  - Associations of the Ratios of n-3 to n-6 Dietary Fatty Acids With Longitudinal
      Changes in Depressive Symptoms Among US Women.
AB  - In the present study, we examined longitudinal changes in self-reported
      depressive symptoms (and related domains) in relation to baseline intakes of n-3
      fatty acids (absolute and relative to n-6 fatty acids). Sex-specific associations
      were evaluated in a prospective cohort of adults (n = 2,053) from Baltimore,
      Maryland, who were 30-64 years of age at baseline and were followed for a mean of
      4.65 (standard deviation, 0.93) years (2004-2013). Using mean intakes of n-3 and
      n-6 fatty acids reported on two 24-hour dietary recalls, we estimated the ratios
      of n-3 to n-6 fatty acids for both highly unsaturated fatty acids (>=20 carbon
      atoms) (HUFAs) and polyunsaturated fatty acids (>=18 carbon atoms) (PUFAs).
      Outcomes included total and domain-specific scores on the 20-item Center for
      Epidemiologic Studies-Depression scale. Based on mixed-effects regression models,
      among women, both higher n-3 HUFA:n-6 PUFA and n-3 PUFA:n-6 PUFA ratios were
      associated with a slower rate of increase in total Center for Epidemiologic
      Studies-Depression scores over time. Higher n-3 HUFA:n-6 HUFA ratios were
      associated with slower increases in somatic complaints in men, whereas among
      women, higher n-3 HUFA:n-6 PUFA and n-3 PUFA:n-6 PUFA ratios were both linked to
      putative longitudinal improvement in positive affect over time. Among US adults,
      n-3:n-6 dietary fatty acid ratio was associated with longitudinal changes in
      depressive symptoms, with a higher ratio linked to a slower increase in
      depressive symptoms over time, particularly among women. 

PMID- 25855647
TI  - Lim et al. respond to "Measurement error and physical activity".

PMID- 25855646
TI  - Measurement error of self-reported physical activity levels in New York City:
      assessment and correction.
AB  - Because it is difficult to objectively measure population-level physical activity
      levels, self-reported measures have been used as a surveillance tool. However,
      little is known about their validity in populations living in dense urban areas.
      We aimed to assess the validity of self-reported physical activity data against
      accelerometer-based measurements among adults living in New York City and to
      apply a practical tool to adjust for measurement error in complex sample data
      using a regression calibration method. We used 2 components of data: 1) dual
      frame random digit dialing telephone survey data from 3,806 adults in 2010-2011
      and 2) accelerometer data from a subsample of 679 survey participants. Self
      reported physical activity levels were measured using a version of the Global
      Physical Activity Questionnaire, whereas data on weekly moderate-equivalent
      minutes of activity were collected using accelerometers. Two self-reported health
      measures (obesity and diabetes) were included as outcomes. Participants with
      higher accelerometer values were more likely to underreport the actual levels.
      (Accelerometer values were considered to be the reference values.) After
      correcting for measurement errors, we found that associations between outcomes
      and physical activity levels were substantially deattenuated. Despite
      difficulties in accurately monitoring physical activity levels in dense urban
      areas using self-reported data, our findings show the importance of performing a
      well-designed validation study because it allows for understanding and correcting
      measurement errors. 

PMID- 25855648
TI  - Invited commentary: meta-physical activity and the search for the truth.
AB  - Measurement error in self-reported data from questionnaires is a well-recognized
      challenge in studies of physical activity and health. In this issue of the
      Journal, Lim et al. (Am J Epidemiol. 2015;181(9):648-655) used data from
      accelerometers in a small measurement study to correct self-reported physical
      activity data from a larger study of adults from New York City and to develop an
      error correction model. They showed that correction of measurement error in self
      reported physical activity levels strengthened the associations of physical
      activity with both obesity and diabetes by 30%-50% compared with using the self
      reported questionnaire data alone. Thus, Lim et al. demonstrated a method to
      improve potentially biased estimates of the association between self-reported
      physical activity and disease. However, as this field develops, we feel it is
      important to call attention to a sometimes overlooked problem that occurs when
      comparing these instruments: Questionnaires and accelerometers are often
      calibrated (i.e., designed) to measure different types of physical activity, and
      accelerometers are still subject to measurement error. Thus, physical activity
      estimates corrected with an imperfect accelerometer measurement might over- or
      undercorrect the strength of the associations. We take this opportunity to
      further comment on physical activity measurement in epidemiologic studies and the
      implications for research. 

PMID- 25855649
TI  - What do you mean, "epigenetic"?
AB  - Interest in the field of epigenetics has increased rapidly over the last decade,
      with the term becoming more identifiable in biomedical research, scientific
      fields outside of the molecular sciences, such as ecology and physiology, and
      even mainstream culture. It has become increasingly clear, however, that
      different investigators ascribe different definitions to the term. Some employ
      epigenetics to explain changes in gene expression, others use it to refer to
      transgenerational effects and/or inherited expression states. This disagreement
      on a clear definition has made communication difficult, synthesis of epigenetic
      research across fields nearly impossible, and has in many ways biased
      methodologies and interpretations. This article discusses the history behind the
      multitude of definitions that have been employed since the conception of
      epigenetics, analyzes the components of these definitions, and offers solutions
      for clarifying the field and mitigating the problems that have arisen due to
      these definitional ambiguities. 

PMID- 25855650
TI  - The expanding genetic toolbox of the wasp Nasonia vitripennis and its relatives.
AB  - The parasitoid wasp Nasonia represents a genus of four species that is emerging
      as a powerful genetic model system that has made and will continue to make
      important contributions to our understanding of evolutionary biology,
      development, ecology, and behavior. Particularly powerful are the haplodiploid
      genetics of the system, which allow some of the advantages of microbial genetics
      to be applied to a complex multicellular eukaryote. In addition, fertile, viable
      hybrids can be made among the four species in the genus. This makes Nasonia
      exceptionally well suited for evolutionary genetics approaches, especially when
      combined with its haploid genetics and tractability in the laboratory. These
      features are complemented by an expanding array of genomic, transcriptomic, and
      functional resources, the application of which has already made Nasonia an
      important model system in such emerging fields as evolutionary developmental
      biology and microbiomics. This article describes the genetic and genomic
      advantages of Nasonia wasps and the resources available for their genetic
      analysis. 

PMID- 25855652
TI  - Corrigendum.

PMID- 25855656
TI  - Innovation team of the year.

PMID- 25855655
TI  - Micro-CT evaluation of microleakage under orthodontic ceramic brackets bonded
      with different bonding techniques and adhesives.
AB  - AIM: The aim of this study was to evaluate microleakage under orthodontic ceramic
      brackets bonded with direct and different indirect bonding techniques and
      adhesives using micro-computed tomography. MATERIALS AND METHODS: A total of 30
      human maxillary premolars were randomly separated into five groups with six teeth
      in each group. In group I, teeth were bonded directly with Transbond XT (3M
      Unitek). In group II, group III, group IV, and group V, teeth were bonded through
      an indirect technique with Custom I.Q. (Reliance Orthodontic Products), Sondhi
      Rapid-Set (3M Unitek), RMbond (RMO), and Transbond IDB (3M Unitek), respectively,
      following the manufacturer's instructions. Micro-CT system model 1172 of Skyscan
      (Kontich, Belgium) was used to scan all samples. NRecon (Skyscan) version 1.6, CT
      Analyser V.1.11 (Skyscan), and TView (SkyScan, Bvba) software programs were used
      for microleakage evaluation. Microleakage values between the test groups were
      assessed using the Kruskal-Wallis test, while the Wilcoxon signed rank test was
      used for within-group comparisons. The level of significance was set at P < 0.05.
      RESULTS: According to the Kruskal-Wallis analysis of variance test, there were no
      significant differences among the tested groups, with regard to volume and
      percentage (microleakage/region of interest * 100) of microleakage values (P <
      0.05). The Wilcoxon signed rank test showed that coronal microleakage volume and
      percentage values significantly differed for RMbond and Transbond IDB groups.
      LIMITATIONS: In the study, only ceramic brackets were used and microleakage into
      mini gaps did not show up on the micro-CT image because 50% silver nitrate
      solution could not penetrate into mini gaps which are smaller than silver nitrate
      particles. CONCLUSION: Use of direct and indirect bonding techniques with
      different adhesives did not significantly affect the amount of microleakage.

PMID- 25855651
TI  - The genomic and genetic toolbox of the teleost medaka (Oryzias latipes).
AB  - The Japanese medaka, Oryzias latipes, is a vertebrate teleost model with a long
      history of genetic research. A number of unique features and established
      resources distinguish medaka from other vertebrate model systems. A large number
      of laboratory strains from different locations are available. Due to a high
      tolerance to inbreeding, many highly inbred strains have been established, thus
      providing a rich resource for genetic studies. Furthermore, closely related
      species native to different habitats in Southeast Asia permit comparative
      evolutionary studies. The transparency of embryos, larvae, and juveniles allows a
      detailed in vivo analysis of development. New tools to study diverse aspects of
      medaka biology are constantly being generated. Thus, medaka has become an
      important vertebrate model organism to study development, behavior, and
      physiology. In this review, we provide a comprehensive overview of established
      genetic and molecular-genetic tools that render medaka fish a full-fledged
      vertebrate system. 

PMID- 25855657
TI  - Arm Abduction Provides a Better Reduction of the Bankart Lesion During
      Immobilization in External Rotation After an Initial Shoulder Dislocation.
AB  - BACKGROUND: Shoulder dislocation often recurs, especially in the younger
      population. Immobilization in external rotation, in which a Bankart lesion is
      displaced in the anterior, medial, and inferior directions, was introduced as a
      new method of nonoperative treatment, but its clinical efficiency is
      controversial. In terms of reducing the lesion, it is reasonable to incorporate
      not only external rotation, which makes the anterior soft tissues tight to push
      the lesion posteriorly and laterally, but also abduction, which makes the
      inferior soft tissues tight to push the lesion superiorly. HYPOTHESIS: Abducting
      the arm during immobilization in external rotation will improve the reduction of
      a Bankart lesion. STUDY DESIGN: Controlled laboratory study. METHODS: There were
      37 patients with initial shoulder dislocation enrolled in this study. After
      reduction, MRI was taken in 4 positions of the shoulder: adduction and internal
      rotation (Add-IR), adduction and external rotation (Add-ER), 30 degrees  of
      abduction and 30 degrees  of external rotation (Abd-30ER), and 30 degrees  of
      abduction and 60 degrees  of external rotation (Abd-60ER). On radial slices, the
      separation, displacement of the labrum, and opening angle of the capsule were
      measured. RESULTS: Add-ER improved the reduction of the anterior labrum but not
      the inferior labrum when compared with Add-IR. Both Abd-30ER and Abd-60ER
      improved the reduction of the inferior labrum as compared with Add-IR.
      Furthermore, Abd-60ER improved the reduction more than Add-ER. CONCLUSION: Among
      the 4 positions tested, Abd-60ER is the best position in terms of reducing the
      Bankart lesion. CLINICAL RELEVANCE: Abducting the shoulder during immobilization
      in external rotation is demonstrated to improve the reduction of the Bankart
      lesion. Therefore, this position is expected to reduce the recurrence rate after
      initial dislocation of the shoulder. Future clinical trials are necessary.

PMID- 25855659
TI  - Modular protein expression by RNA trans-splicing enables flexible expression of
      antibody formats in mammalian cells from a dual-host phage display vector.
AB  - A recently described dual-host phage display vector that allows expression of
      immunoglobulin G (IgG) in mammalian cells bypasses the need for subcloning of
      phage display clone inserts to mammalian vectors for IgG expression in large
      antibody discovery and optimization campaigns. However, antibody discovery and
      optimization campaigns usually need different antibody formats for screening,
      requiring reformatting of the clones in the dual-host phage display vector to an
      alternative vector. We developed a modular protein expression system mediated by
      RNA trans-splicing to enable the expression of different antibody formats from
      the same phage display vector. The heavy-chain region encoded by the phage
      display vector is directly and precisely fused to different downstream heavy
      chain sequences encoded by complementing plasmids simply by joining exons in
      different pre-mRNAs by trans-splicing. The modular expression system can be used
      to efficiently express structurally correct IgG and Fab fragments or other
      antibody formats from the same phage display clone in mammalian cells without
      clone reformatting. 

PMID- 25855658
TI  - Cytokine refacing effect reduces granulocyte macrophage colony-stimulating factor
      susceptibility to antibody neutralization.
AB  - Crohn's Disease (CD) afflicts over half a million Americans with an annual
      economic impact exceeding $10 billion. Granulocyte macrophage colony-stimulating
      factor (GM-CSF) can increase patient immune responses against intestinal microbes
      that promote CD and has been effective for some patients in clinical trials. We
      have made important progress toward developing GM-CSF variants that could be more
      effective CD therapeutics by virtue of being less prone to neutralization by the
      endogenous GM-CSF autoantibodies that are highly expressed in CD patients. Yeast
      display engineering revealed mutations that increase GM-CSF variant binding
      affinity by up to ~3-fold toward both GM-CSF receptor alpha and beta subunits in
      surface plasmon resonance experiments. Increased binding affinity did not reduce
      GM-CSF half-maximum effective concentration (EC50) values in conventional in
      vitro human leukocyte proliferation assays. Affinity-enhancing mutations did,
      however, promote a 'refacing effect' that imparted all five evaluated GM-CSF
      variants with increased in vitro bioactivity in the presence of GM-CSF
      neutralizing polyclonal antisera. The most improved variant, H15L/R23L, was 6
      fold more active than wild-type GM-CSF. Incorporation of additional known
      affinity-increasing mutations could augment the refacing effect and concomitant
      bioactivity improvements described here. 

PMID- 25855660
TI  - Anti-Semaphorin 3A neutralization monoclonal antibody prevents sepsis development
      in lipopolysaccharide-treated mice.
AB  - Semaphorin 3A (Sema3A), originally identified as a potent growth cone collapsing
      factor in developing sensory neurons, is now recognized as a key player in
      immune, cardiovascular, bone metabolism and neurological systems. Here we
      established an anti-Sema3A monoclonal antibody that neutralizes the effects of
      Sema3A both in vitro and in vivo. The anti-Sema3A neutralization chick IgM
      antibodies were screened by combining an autonomously diversifying library
      selection system and an in vitro growth cone collapse assay. We further developed
      function-blocking chick-mouse chimeric and humanized anti-Sema3A antibodies. We
      found that our anti-Sema3A antibodies were effective for improving the survival
      rate in lipopolysaccharide-induced sepsis in mice. Our antibody is a potential
      therapeutic agent that may prevent the onset of or alleviate symptoms of human
      diseases associated with Sema3A. 

PMID- 25855661
TI  - Resveratrol inhibits the acetylated alpha-tubulin-mediated assembly of the NLRP3
      inflammasome.
AB  - With its adaptor protein apoptosis-associated speck-like protein containing a
      caspase recruitment domain (ASC), Nod-like receptor family, pyrin domain
      containing 3 (NLRP3) forms the inflammasome and mediates inflammatory innate
      immune responses. Development of an anti-inflammatory drug targeting the NLRP3
      inflammasome is urgently required because its aberrant activation often causes
      inflammatory diseases, including gout. We show that resveratrol, a natural
      polyphenol in grapes and wine, is a safe and effective phytochemical that
      inhibits NLRP3-inflammasome activation. Resveratrol inhibits the accumulation of
      acetylated alpha-tubulin caused by mitochondrial damage in macrophages stimulated
      with inducers of the NLRP3-inflammasome. Consequently, resveratrol inhibits the
      acetylated-alpha-tubulin-mediated spatial arrangement of mitochondria and their
      subsequent contact with the endoplasmic reticulum (ER), causing insufficient
      assembly of ASC on the mitochondria and NLRP3 on the ER. These findings indicate
      that resveratrol targets the generation of an optimal site for the assembly of
      NLRP3 and ASC, thus inhibiting NLRP3-inflammasome activation. Therefore,
      resveratrol could be an effective medication for the treatment of NLRP3-related
      inflammatory diseases. 

PMID- 25855662
TI  - To do it or not to do it? How communally motivated people navigate sexual
      interdependence dilemmas.
AB  - The current research investigates how people make sexual decisions when romantic
      partners' sexual desires conflict, situations we refer to as sexual
      interdependence dilemmas. Across an experimental study, a retrospective recall
      study, and a 21-day daily experience study, we found that people who were
      motivated to meet their partner's sexual needs--those high in sexual communal
      strength--were more willing to engage in sex with their romantic partner, even
      when their own desire was low, and as a result, both partners reported enhanced
      relationship and sexual satisfaction. The benefits of sexual communal strength
      were due to communally oriented people's increased desire to promote their
      partner's interests and decreased desire to pursue their own interests. This is
      the first set of studies to investigate how people make decisions in sexual
      interdependence dilemmas and show that communally motivated individuals navigate
      these situations in a way that is beneficial for relationships.

PMID- 25855663
TI  - Seasonal trends in photosynthesis and electron transport during the Mediterranean
      summer drought in leaves of deciduous oaks.
AB  - The California Mediterranean savanna has harsh summer conditions with minimal
      soil moisture, high temperature, high incoming solar radiation and little or no
      precipitation. Deciduous blue oaks, Quercus douglasii Hook. and Arn., are winter
      deciduous obligate phreatophytes, transpiring mostly groundwater throughout the
      summer drought. The objective of this work is to fully characterize the seasonal
      trends of photosynthesis in blue oaks as well as the mechanistic relationships
      between leaf structure and function. We estimate radiative load of the leaves via
      the FLiES model and perform in situ measurements of leaf water potential, leaf
      nitrogen content, an index of chlorophyll content (SPAD readings), photosynthetic
      and electron transport capacity, and instantaneous rates of CO2 assimilation and
      electron transport. We measured multiple trees over 3 years providing data from a
      range of conditions. Our study included one individual that demonstrated strong
      drought stress as indicated by changes in SPAD readings, leaf nitrogen and all
      measures of leaf functioning. In the year following severe environmental stress,
      one individual altered foliation patterns on the crown but did not die. In all
      other individuals, we found that net carbon assimilation and photosynthetic
      capacity decreased during the summer drought. SPAD values, electron transport
      rate (ETR) and quantum yield of photosystem II (PSII) did not show a strong
      decrease during the summer drought. In most individuals, PSII activity and SPAD
      readings did not indicate leaf structural or functional damage throughout the
      season. While net carbon assimilation was tightly coupled to stomatal
      conductance, the coupling was not as tight with ETR possibly due to contributions
      from photorespiration or other protective processes. Our work demonstrates that
      the blue oaks avoid structural damage by maintaining the capacity to convert and
      dissipate incoming solar radiation during the hot summer drought and are
      effective at fixing carbon by maximizing rates during the mild spring conditions.

PMID- 25855664
TI  - The PRONE score: an algorithm for predicting doctors' risks of formal patient
      complaints using routinely collected administrative data.
AB  - BACKGROUND: Medicolegal agencies-such as malpractice insurers, medical boards and
      complaints bodies-are mostly passive regulators; they react to episodes of
      substandard care, rather than intervening to prevent them. At least part of the
      explanation for this reactive role lies in the widely recognised difficulty of
      making robust predictions about medicolegal risk at the individual clinician
      level. We aimed to develop a simple, reliable scoring system for predicting
      Australian doctors' risks of becoming the subject of repeated patient complaints.
      METHODS: Using routinely collected administrative data, we constructed a national
      sample of 13,849 formal complaints against 8424 doctors. The complaints were
      lodged by patients with state health service commissions in Australia over a 12
      year period. We used multivariate logistic regression analysis to identify
      predictors of subsequent complaints, defined as another complaint occurring
      within 2 years of an index complaint. Model estimates were then used to derive a
      simple predictive algorithm, designed for application at the doctor level.
      RESULTS: The PRONE (Predicted Risk Of New Event) score is a 22-point scoring
      system that indicates a doctor's future complaint risk based on four variables: a
      doctor's specialty and sex, the number of previous complaints and the time since
      the last complaint. The PRONE score performed well in predicting subsequent
      complaints, exhibiting strong validity and reliability and reasonable goodness of
      fit (c-statistic=0.70). CONCLUSIONS: The PRONE score appears to be a valid method
      for assessing individual doctors' risks of attracting recurrent complaints.
      Regulators could harness such information to target quality improvement
      interventions, and prevent substandard care and patient dissatisfaction. The
      approach we describe should be replicable in other agencies that handle large
      numbers of patient complaints or malpractice claims.

PMID- 25855665
TI  - Diagnostic imaging of pancreatic neuroendocrine neoplasms (pNEN): tumor
      detection, staging, prognosis, and response to treatment.
AB  - Pancreatic neuroendocrine neoplasms (pNEN) are rare malignancies arising from
      neuroendocrine cells of the pancreas. Functional tumors can present with specific
      clinical syndromes due to hormonal secretion. These tumors can present as
      incidental findings on imaging performed for unrelated purposes or they are
      diagnosed when workup is initiated in patients with specific syndromes or
      metastases. This article presents an overview of available imaging techniques
      focusing on computed tomography and magnetic resonance imaging. Recommendations
      regarding examination protocols are given. Typical imaging features of pNEN and
      metastases are described. Their potential value for the evaluation of prognosis
      as well as tumor response under treatment is discussed. 

PMID- 25855666
TI  - A comparison of liver fat content as determined by magnetic resonance imaging
      proton density fat fraction and MRS versus liver histology in non-alcoholic fatty
      liver disease.
AB  - BACKGROUND: Many imaging methods have been defined for quantification of hepatic
      steatosis in non-alcoholic fatty liver disease (NAFLD). However, studies
      comparing the efficiency of magnetic resonance imaging-proton density fat
      fraction (MRI-PDFF), magnetic resonance spectroscopy (MRS), and liver histology
      for quantification of liver fat content are limited. PURPOSE: To compare the
      efficiency of MRI-PDFF and MRS in the quantification of liver fat content in
      individuals with NAFLD. MATERIAL AND METHODS: A total of 19 NAFLD patients
      underwent MRI-PDFF, MRS, and liver biopsy for quantification of liver fat
      content. The MR examinations were performed on a 1.5 HDx MRI system. The MRI
      protocol included T1-independent volumetric multi-echo gradient-echo imaging with
      T2* correction and spectral fat modeling and MRS with STEAM technique. RESULTS: A
      close correlation was observed between liver MRI-PDFF- and histology- determined
      steatosis (r = 0.743, P < 0.001) and between liver MRS- and histology-determined
      steatosis (r = 0.712, P < 0.001), with no superiority between them (z = 0.19, P =
      0.849). For quantification of hepatic steatosis, a high correlation was observed
      between the two MRI methods (r = 0.986, P < 0.001). MRI-PDFF and MRS accurately
      differentiated moderate/severe steatosis from mild/no hepatic steatosis (P =
      0.007 and 0.013, respectively), with no superiority between them (AUCMRI-PDFF =
      0.881 +/- 0.0856 versus AUCMRS = 0.857 +/- 0.0924, P = 0.461). CONCLUSION: Both
      MRI-PDFF and MRS can be used for accurate quantification of hepatic steatosis.

PMID- 25855667
TI  - Modified thoracolumbar injury classification and severity score (TLICS) and its
      clinical usefulness.
AB  - BACKGROUND: Thoracolumbar injury classification and severity score (TLICS) is not
      very reliable for assessment of injury to the posterior ligament complex, even
      when scored by experts. It is not reasonable to score every compression fracture
      or burst fracture the same as there is great variety in the severity of
      compression fractures and burst fractures. PURPOSE: To propose a modified TLICS
      (mTLICS) and evaluate the performance of the mTLICS system by measuring the
      agreement between scores determined by radiologists using both systems and actual
      treatment procedure delivered. MATERIAL AND METHODS: We retrospectively evaluated
      134 patients with acute lumbar and thoracic spinal trauma after undergoing
      magnetic resonance imaging (MRI) using new mTLICS and conventional TLICS system.
      Inter-observer agreements of TLICS and mTLICS scores were analyzed using the
      kappa statistic. Nonparametric correlation analysis was used to determine
      correlation (R) among each score and the surgical intervention. RESULTS: The
      mTLICS system showed slightly higher correlation than TLICS (Rs, TLICS, 0.592 and
      0.613 vs. mTLICS, 0.628 and 0.639). If we consider a total maximal score of 4 to
      be a negative surgical indication, mTLICS showed significantly higher
      sensitivities than TLICS, and if we consider a total minimal score of 4 to be a
      positive surgical indication, mTLICS showed significantly higher specificities
      than TLICS. CONCLUSION: The mTLICS score corrects deficiencies in the TLICS
      system that lead to ambiguity in the radiological diagnostic criteria. mTLICS is
      a more suitable scoring system than TLICS for predicting surgical management
      accurately, especially for morphological injuries.

PMID- 25855668
TI  - Pulmonary artery enlargement is associated with right ventricular dysfunction and
      loss of blood volume in small pulmonary vessels in chronic obstructive pulmonary
      disease.
AB  - BACKGROUND: Chronic obstructive pulmonary disease causes significant morbidity
      and concomitant pulmonary vascular disease and cardiac dysfunction are associated
      with poor prognosis. Computed tomography-detected relative pulmonary artery (PA)
      enlargement defined as a PA to ascending aorta diameter ratio >1 (PA:A>1) is a
      marker for pulmonary hypertension and predicts chronic obstructive pulmonary
      disease exacerbations. However, little is known about the relationship between
      the PA:A ratio, pulmonary blood volume, and cardiac function. METHODS AND
      RESULTS: A single-center prospective cohort study of patients with chronic
      obstructive pulmonary disease was conducted. Clinical characteristics and
      computed tomography metrics, including the PA:A and pulmonary blood vessel
      volume, were measured. Ventricular functions, volumes, and dimensions were
      measured by cine cardiac MRI with 3-dimensional analysis. Linear regression
      examined the relationships between clinical characteristics, computed tomography
      and cardiac MRI metrics, and 6-minute walk distance. Twenty-four patients were
      evaluated and those with PA:A>1 had higher right ventricular (RV) end-diastolic
      and end-systolic volume indices accompanied by lower RV ejection fraction (52+/
      7% versus 60+/-9%; P=0.04). The PA:A correlated inversely with total
      intraparenchymal pulmonary blood vessel volume and the volume of distal vessels
      with a cross-sectional area of <5 mm(2). Lower forced expiratory volume, PA:A>1,
      and hyperinflation correlated with reduced RV ejection fraction. Both PA diameter
      and reduced RV ejection fraction were independently associated with reduced 6
      minute walk distance. CONCLUSIONS: The loss of blood volume in distal pulmonary
      vessels is associated with PA enlargement on computed tomography. Cardiac MRI
      detects early RV dysfunction and remodeling in nonsevere chronic obstructive
      pulmonary disease patients with a PA:A>1. Both RV dysfunction and PA enlargement
      are independently associated with reduced walk distance. CLINICAL TRIAL
      REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00608764.

PMID- 25855669
TI  - Contrast-enhanced ultrasound assessment of impaired adipose tissue and muscle
      perfusion in insulin-resistant mice.
AB  - BACKGROUND: In diabetes mellitus, reduced perfusion and capillary surface area in
      skeletal muscle, which is a major glucose storage site, contribute to abnormal
      glucose homeostasis. Using contrast-enhanced ultrasound, we investigated whether
      abdominal adipose tissue perfusion is abnormal in insulin resistance and
      correlates with glycemic control. METHODS AND RESULTS: Contrast-enhanced
      ultrasound perfusion imaging of abdominal adipose tissue and skeletal muscle was
      performed in obese insulin resistance (db/db) mice at 11 to 12 or 14 to 16 weeks
      of age and in control lean mice. Time-intensity data were analyzed to quantify
      microvascular blood flow (MBF) and capillary blood volume (CBV). Blood glucose
      response for 1 hour was measured after insulin challenge (1 U/kg, IP). Compared
      with control mice, db/db mice at 11 to 12 and 14 to 16 weeks had a higher glucose
      concentration area under the curve after insulin (11.8+/-2.8, 20.6+/-4.3, and
      28.4+/-5.9 mg.min/dL [*1000], respectively; P=0.0002) and also had lower adipose
      MBF (0.094+/-0.038, 0.035+/-0.010, and 0.023+/-0.01 mL/min per gram; P=0.0002)
      and CBV (1.6+/-0.6, 1.0+/-0.3, and 0.5+/-0.1 mL/100 g; P=0.0017). The glucose
      area under the curve correlated in a nonlinear fashion with both adipose and
      skeletal muscle MBF and CBV. There were significant linear correlations between
      adipose and muscle MBF (r=0.81) and CBV (r=0.66). Adipocyte cell volume on
      histology was 25-fold higher in 14- to 16-week db/db versus control mice.
      CONCLUSIONS: Abnormal adipose MBF and CBV in insulin resistance can be detected
      by contrast-enhanced ultrasound and correlates with the degree of impairment in
      glucose storage. Abnormalities in adipose tissue and muscle seem to be coupled.
      Impaired adipose tissue perfusion is in part explained by an increase in
      adipocyte size without proportional vascular response.

PMID- 25855671
TI  - Clinical leadership team of the year.

PMID- 25855670
TI  - Molecular analysis of the cumulus matrix: insights from mice with O-glycan
      deficient oocytes.
AB  - During follicle development, oocytes secrete factors that influence the
      development of granulosa and cumulus cells (CCs). In response to oocyte and
      somatic cell signals, CCs produce extracellular matrix (ECM) molecules resulting
      in cumulus expansion, which is essential for ovulation, fertilisation, and is
      predictive of oocyte quality. The cumulus ECM is largely made up of hyaluronan
      (HA), TNF-stimulated gene-6 (TSG-6, also known as TNFAIP6), pentraxin-3 (PTX3),
      and the heavy chains (HCs) of serum-derived inter-alpha-inhibitor proteins. In
      contrast to other in vivo models where modified expansion impairs fertility, the
      cumulus mass of C1galt1 Mutants, which have oocyte-specific deletion of core 1
      derived O-glycans, is modified without impairing fertility. In this report, we
      used C1galt1 Mutant (C1galt1(FF):ZP3Cre) and Control (C1galt1(FF)) mice to
      investigate how cumulus expansion is affected by oocyte-specific deletion of core
      1-derived O-glycans without adversely affecting oocyte quality. Mutant cumulus
      oocyte complexes (COCs) are smaller than Controls, with fewer CCs. Interestingly,
      the CCs in Mutant mice are functionally normal as each cell produced normal
      levels of the ECM molecules HA, TSG-6, and PTX3. However, HC levels were elevated
      in Mutant COCs. These data reveal that oocyte glycoproteins carrying core 1
      derived O-glycans have a regulatory role in COC development. In addition, our
      study of Controls indicates that a functional COC can form provided all essential
      components are present above a minimum threshold level, and thus some variation
      in ECM composition does not adversely affect oocyte development, ovulation or
      fertilisation. These data have important implications for IVF and the use of
      cumulus expansion as a criterion for oocyte assessment. 

PMID- 25855672
TI  - Epidemiology of Hospital System Patient Falls: A Retrospective Analysis.
AB  - Patient falls are the most common type of in-hospital accidents. The objective of
      this retrospective descriptive study was to describe the locations and
      characteristics of hospital-related falls. Data on patient characteristics,
      including locations and fall circumstances, were collected through incident
      reports and medical records. A total of 1822 falls were documented at a 921-bed,
      urban academic hospital center over a one-year period; 1767 (97.0%) of the falls
      occurred in the hospital setting, 55 (3.0%) in ambulatory care. The majority of
      falls (80.8%) occurred within inpatient units; the remainder within the greater
      hospital campus. In all, 73.4% of fallers had fall prevention protocols
      implemented prior to the fall. The youngest age group (<=49 years) had the
      highest percentage of fallers. This study provides novel insights into variables
      found to be associated with falling, including location of falls within the
      hospital campus, efficacy of fall prevention protocols, and age groups.

PMID- 25855673
TI  - The Health Innovations Scholars Program: A Model for Accelerating Preclinical
      Medical Students' Mastery of Skills for Leading Improvement of Clinical Systems.
AB  - Dramatic changes in health care require physician leadership. Efforts to instill
      necessary skills often occur late in training. The Heath Innovations Scholars
      Program (HISP) provided preclinical medical students with experiential learning
      focused on process improvement. Students led initiatives to improve the discharge
      process for stroke patients. All students completed an aptitude survey and
      Quality Improvement Knowledge Assessment Test (QIKAT) before and after the
      program. Significant improvements occurred across subject areas of leadership
      (18.4%, P < .001), quality and safety (14.7%, P < .001), and health care systems
      operations (21.2%, P < .008), and in the domains of knowledge (25.9%, P < .001)
      and skills (25.2%, P < .001). Average cumulative QIKAT results improved
      significantly (8.33 to 9.83, P = .04). Three of 4 recommended interventions were
      implemented. Furthermore, students engaged in other process improvement work on
      return to their home institutions. The HISP successfully advanced preclinical
      medical students' ability to lead clinical systems improvement.

PMID- 25855674
TI  - Evidence that conflict regarding size of haemodynamic response to
      interventricular delay optimization of cardiac resynchronization therapy may
      arise from differences in how atrioventricular delay is kept constant.
AB  - AIMS: Whether adjusting interventricular (VV) delay changes haemodynamic efficacy
      of cardiac resynchronization therapy (CRT) is controversial, with conflicting
      results. This study addresses whether the convention for keeping atrioventricular
      (AV) delay constant during VV optimization might explain these conflicts. METHOD
      AND RESULTS: Twenty-two patients in sinus rhythm with existing CRT underwent VV
      optimization using non-invasive systolic blood pressure. Interventricular
      optimization was performed with four methods for keeping the AV delay constant:
      (i) atrium and left ventricle delay kept constant, (ii) atrium and right
      ventricle delay kept constant, (iii) time to the first-activated ventricle kept
      constant, and (iv) time to the second-activated ventricle kept constant. In 11
      patients this was performed with AV delay of 120 ms, and in 11 at AV optimum. At
      AV 120 ms, time to the first ventricular lead (left or right) was the
      overwhelming determinant of haemodynamics (13.75 mmHg at +/-80 ms, P < 0.001)
      with no significant effect of time to second lead (0.47 mmHg, P = 0.50), P <
      0.001 for difference. At AV optimum, time to first ventricular lead again had a
      larger effect (5.03 mmHg, P < 0.001) than time to second (2.92 mmHg, P = 0.001),
      P = 0.02 for difference. CONCLUSION: Time to first ventricular activation is the
      overwhelming determinant of circulatory function, regardless of whether this is
      the left or right ventricular lead. If this is kept constant, the effect of
      changing time to the second ventricle is small or nil, and is not beneficial. In
      practice, it may be advisable to leave VV delay at zero. Specifying how AV delay
      is kept fixed might make future VV delay research more enlightening.

PMID- 25855676
TI  - Impact of haematoma after pacemaker and CRT device implantation on
      hospitalization costs, length of stay, and mortality: a population-based study.
AB  - AIMS: Pocket haematoma is a common complication following pacemaker implantation.
      Impact of this complication on post-procedural outcomes has previously not been
      systematically studied. We sought to identify the incidence of pocket haematoma
      after a de novo pacemaker and cardiac resynchronization therapy (CRT) device
      implantation and evaluate its impact on the hospital outcomes using a large all
      payer national inpatient database. METHODS AND RESULTS: Data from Nationwide
      Inpatient Sample 2010 was queried to identify all primary implantations of single
      chamber, dual chamber pacemakers, and biventricular devices during the year 2010
      using the appropriate ICD-9 codes. Patients who experienced a procedure-related
      haematoma during the hospital stay were identified. Of a total of 78,751 primary
      pacemaker implantations in the year 2010, 1677 (2.1%) of the implantations were
      complicated by a pocket haematoma. Higher age groups, more complex pacemaker
      types (BiV > dual chamber > single chamber), and comorbidities such as congestive
      heart failure and coagulopathy were associated with an increased risk of pocket
      haematoma formation post-pacemaker implantation. Patients who developed a pocket
      haematoma had a longer length of stay (8.7 vs. 4.8 days, P < 0.001), higher
      hospitalization costs ($48,815 vs. $34,324, P < 0.001) and higher in-hospital
      mortality (2.0 vs. 0.7%, P < 0.001) compared with patients who did not develop a
      haematoma. CONCLUSIONS: Haematoma is a relatively common complication associated
      with pacemaker implantation; however, it adversely impacts in-hospital outcomes.

PMID- 25855675
TI  - Comparison of the new risk prediction model (HCM Risk-SCD) and classic risk
      factors for sudden death in patients with hypertrophic cardiomyopathy and
      defibrillator.
AB  - AIMS: Hypertrophic cardiomyopathy is one of the main causes of sudden death in
      young people. Recent clinical practice guidelines include a risk prediction model
      for sudden death (HCM Risk-SCD), which facilitates the decision of whether to
      implant a defibrillator. The aim of our study was to ascertain the percentage of
      events in our series of primary prevention implantable cardioverter-defibrillator
      recipients with hypertrophic cardiomyopathy and whether HCM Risk-SCD predicts the
      onset of arrhythmic events. METHODS AND RESULTS: This was an observational,
      retrospective cohort study, which included 48 primary prevention defibrillator
      recipient patients with HCM. We compiled their demographic and clinical
      characteristics, estimated 5-year risk using HCM Risk-SCD, and collected the
      documentation on arrhythmias during follow-up. The majority was male (66.7%) and
      mean age at implantation was 44.44 +/- 14.46 years. Non-sustained ventricular
      tachycardia was the most prevalent risk factor (66.67%), followed by a family
      history of sudden death (47.92%). Mean HCM Risk-SCD was 6.15 +/- 5.01%. HCM Risk
      SCD was the only factor independently associated with the onset of ventricular
      tachyarrhythmia, above any other classic risk factor or association [odds ratio =
      1.46 (95% confidence interval 1.051-2.013); P = 0.02]. None of the 11 patients
      estimated as low risk using HCM Risk-SCD suffered any appropriate events (P <
      0.05). CONCLUSIONS: During an average follow-up of 4 years, 16.67% presented
      appropriate events (4.16%/year). HCM Risk-SCD predicted the onset of events more
      suitably than classic risk factors.

PMID- 25855677
TI  - The rationale and design of the Micra Transcatheter Pacing Study: safety and
      efficacy of a novel miniaturized pacemaker.
AB  - AIMS: Recent advances in miniaturization technologies and battery chemistries
      have made it possible to develop a pacemaker small enough to implant within the
      heart while still aiming to provide similar battery longevity to conventional
      pacemakers. The Micra Transcatheter Pacing System is a miniaturized single
      chamber pacemaker system that is delivered via catheter through the femoral vein.
      The pacemaker is implanted directly inside the right ventricle of the heart,
      eliminating the need for a device pocket and insertion of a pacing lead, thereby
      potentially avoiding some of the complications associated with traditional pacing
      systems. METHODS AND RESULTS: The Micra Transcatheter Pacing Study is currently
      undergoing evaluation in a prospective, multi-site, single-arm study.
      Approximately 720 patients will be implanted at up to 70 centres around the
      world. The study is designed to have a continuously growing body of evidence and
      data analyses are planned at various time points. The primary safety and efficacy
      objectives at 6-month post-implant are to demonstrate that (i) the percentage of
      Micra patients free from major complications related to the Micra system or
      implant procedure is significantly higher than 83% and (ii) the percentage of
      Micra patients with both low and stable thresholds is significantly higher than
      80%. The safety performance benchmark is based on a reference dataset of 977
      subjects from 6 recent pacemaker studies. CONCLUSIONS: The Micra Transcatheter
      Pacing Study will assess the safety and efficacy of a miniaturized, totally
      endocardial pacemaker in patients with an indication for implantation of a single
      chamber ventricular pacemaker. CLINICALTRIALSGOV REGISTRATION ID: NCT02004873.

PMID- 25855678
TI  - Effect of antihypertensive agents on risk of atrial fibrillation: a meta-analysis
      of large-scale randomized trials.
AB  - AIMS: High blood pressure is known to be associated with future risk of atrial
      fibrillation. Whether such risks can be reduced with antihypertensive therapy is
      less clear. We conducted a systematic review and meta-analysis of large-scale
      randomized trials that have reported the effect of antihypertensive agents on
      atrial fibrillation. METHODS AND RESULTS: MEDLINE was searched for randomized
      trials published between 1966 and February 2014. Randomized, controlled trials
      were eligible for inclusion if they tested an antihypertensive agent and reported
      atrial fibrillation as an outcome. Atrial fibrillation, reported as trial outcome
      or adverse event, and study characteristics were extracted by investigators. In
      27 trials with 214 763 randomized participants and 9929 events of atrial
      fibrillation, pooled using inverse-variance weighted fixed effects meta-analysis,
      antihypertensive therapy reduced the risk of atrial fibrillation by 10% [risk
      ratio (RR) 0.90; 95% confidence interval (CI) 0.86, 0.94]. However, the
      proportional effects differed significantly between trials (P < 0.001 for
      heterogeneity). In trials that included patients with no prior heart disease, or
      patients with coronary artery disease but no heart failure, no significant
      effects were found (RR 1.02; CI 0.88, 1.18 and RR 0.95; CI 0.89, 1.01,
      respectively). Conversely, proportional effects were larger in trials that
      predominantly included patients with heart failure (RR 0.81; CI 0.74, 0.87). When
      classes of medication were compared against each other, no significant
      differences in effects on atrial fibrillation were observed. CONCLUSIONS:
      Antihypertensive therapy reduces the risk of atrial fibrillation modestly but
      benefits appear to be larger in patients with heart failure, with no clear
      evidence of benefit in patients without heart failure. Previous suggestions of
      class-specific effects could not be confirmed in this more comprehensive
      analysis.

PMID- 25855679
TI  - Effect of tricuspid regurgitation and the right heart on survival after
      transcatheter aortic valve replacement: insights from the Placement of Aortic
      Transcatheter Valves II inoperable cohort.
AB  - BACKGROUND: Tricuspid regurgitation (TR) and right ventricular (RV) dysfunction
      adversely affect outcomes in patients with heart failure or mitral valve disease,
      but their impact on outcomes in patients with aortic stenosis treated with
      transcatheter aortic valve replacement has not been well characterized. METHODS
      AND RESULTS: Among 542 patients with symptomatic aortic stenosis treated in the
      Placement of Aortic Transcatheter Valves (PARTNER) II trial (inoperable cohort)
      with a Sapien or Sapien XT valve via a transfemoral approach, baseline TR
      severity, right atrial and RV size and RV function were evaluated by
      echocardiography according to established guidelines. One-year mortality was
      16.9%, 17.2%, 32.6%, and 61.1% for patients with no/trace (n=167), mild (n=205),
      moderate (n=117), and severe (n=18) TR, respectively (P<0.001). Increasing
      severity of RV dysfunction as well as right atrial and RV enlargement were also
      associated with increased mortality (P<0.001). After multivariable adjustment,
      severe TR (hazard ratio, 3.20; 95% confidence interval, 1.50-6.82; P=0.003) and
      moderate TR (hazard ratio, 1.60; 95% confidence interval, 1.02-2.52; P=0.042)
      remained associated with increased mortality as did right atrial and RV
      enlargement, but not RV dysfunction. There was an interaction between TR and
      mitral regurgitation severity (P=0.04); the increased hazard of death associated
      with moderate/severe TR only occurred in those with no/trace/mild mitral
      regurgitation. CONCLUSIONS: In inoperable patients treated with transcatheter
      aortic valve replacement, moderate or severe TR and right heart enlargement are
      independently associated with increased 1-year mortality; however, the
      association between moderate or severe TR and an increased hazard of death was
      only found in those with minimal mitral regurgitation at baseline. These findings
      may improve our assessment of anticipated benefit from transcatheter aortic valve
      replacement and support the need for future studies on TR and the right heart,
      including whether concomitant treatment of TR in operable but high-risk patients
      with aortic stenosis is warranted. CLINICAL TRIAL REGISTRATION: URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT01314313.

PMID- 25855680
TI  - Efficacy and safety of a novel bioabsorbable polymer-coated, everolimus-eluting
      coronary stent: the EVOLVE II Randomized Trial.
AB  - BACKGROUND: Drug eluting stents with durable polymers may be associated with
      hypersensitivity, delayed healing, and incomplete endothelialization, which may
      contribute to late/very late stent thrombosis and the need for prolonged dual
      antiplatelet therapy. Bioabsorbable polymers may facilitate stent healing, thus
      enhancing clinical safety. The SYNERGY stent is a thin-strut, platinum chromium
      metal alloy platform with an ultrathin bioabsorbable Poly(D,L-lactide-co
      glycolide) abluminal everolimus-eluting polymer. We performed a multicenter,
      randomized controlled trial for regulatory approval to determine noninferiority
      of the SYNERGY stent to the durable polymer PROMUS Element Plus everolimus
      eluting stent. METHODS AND RESULTS: Patients (n=1684) scheduled to undergo
      percutaneous coronary intervention for non-ST-segment-elevation acute coronary
      syndrome or stable coronary artery disease were randomized to receive either the
      SYNERGY stent or the PROMUS Element Plus stent. The primary end point of 12-month
      target lesion failure was observed in 6.7% of SYNERGY and 6.5% PROMUS Element
      Plus treated subjects by intention-to-treat (P=0.83 for difference; P=0.0005 for
      noninferiority), and 6.4% in both the groups by per-protocol analysis (P=0.0003
      for noninferiority). Clinically indicated revascularization of the target lesion
      or definite/probable stent thrombosis were observed in 2.6% versus 1.7% (P=0.21)
      and 0.4% versus 0.6% (P=0.50) of SYNERGY versus PROMUS Element Plus-treated
      subjects, respectively. CONCLUSIONS: In this randomized trial, the SYNERGY
      bioabsorbable polymer everolimus-eluting stent was noninferior to the PROMUS
      Element Plus everolimus-eluting stent with respect to 1-year target lesion
      failure. These data support the relative safety and efficacy of SYNERGY in a
      broad range of patients undergoing percutaneous coronary intervention. CLINICAL
      TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier:
      NCT01665053.

PMID- 25855681
TI  - Effect of right ventricular function and tricuspid regurgitation on outcomes
      after transcatheter aortic valve implantation: forgotten side of the heart.

PMID- 25855682
TI  - Characterisation of porcine dermis scaffolds decellularised using a novel non
      enzymatic method for biomedical applications.
AB  - Off-the-shelf availability of tissue-engineered skin constructs, tailored by
      different combinations of reagents to produce a highly preserved biological
      matrix is often the only means to help patients suffering skin damage. This study
      assessed the effect of five different decellularisation methods on porcine dermal
      scaffolds with regard to matrix composition, biomechanical strength, and
      cytotoxicity using an in vitro biocompatibility assay. Results demonstrated that
      four out of the five tested decellularisation protocols were efficient in
      producing acellular scaffolds. Nevertheless, decellularisation method using
      osmotic shock without enzymatic digestion showed to be efficient not only in
      removing cellular material and debris from dermal scaffolds but was also
      beneficial in the preservation of extracellular matrix components
      (glycosaminoglycans and collagen). Histological assessment revealed that the
      dermal architecture of coarse collagen bundles was preserved. Examinations by
      scanning electron microscopy and transmission electron microscopy showed that the
      arrangement and ultrastructure of collagen fibrils in the scaffolds were retained
      following non-enzymatic method of decellularisation and also after collagen
      crosslinking using genipin. Moreover, this decellularised scaffold was not only
      shown to be biologically compatible when co-cultured with bone marrow-derived
      mesenchymal stem cells and fibroblasts, but also stimulated the cells to release
      trophic factors essential for tissue regeneration. 

PMID- 25855683
TI  - Study on inhibitory activity of chitosan-based materials against biofilm
      producing Pseudomonas aeruginosa strains.
AB  - Six antibiotic-resistant Pseudomonas aeruginosa strains, isolated from chronic
      diabetic foot infections, were chosen for studying the influence of different
      chitosan-based materials: chitosan solution and chitosan submicroparticles in
      both planktonic and 24 h-old biofilm-forming models. Chitosan solution occurred
      to be more effective in the reduction of bacterial populations than chitosan
      submicroparticles for both planktonic and biofilm-related Pseudomonas cells. It
      seems that the antimicrobial activity of the tested chitosan preparations depends
      on the individual bacterial strain susceptibility probably related to differences
      in the phenotypes and natural antioxidant abilities of Pseudomonas aeruginosa
      strains. 

PMID- 25855684
TI  - Occurrence of stuttering priapism on low dose of quetiapine.

PMID- 25855685
TI  - Toward understanding the heterogeneity in obsessive-compulsive disorder: Evidence
      from narratives in adult patients.
AB  - BACKGROUND: Current attempts at understanding the heterogeneity in obsessive
      compulsive disorder have relied on quantitative methods. The results of such work
      point toward a dimensional structure for obsessive-compulsive disorder. Existing
      qualitative work in obsessive-compulsive disorder has focused on understanding
      specific aspects of the obsessive-compulsive disorder experience in greater
      depth. However, qualitative methods are also of potential value in furthering our
      understanding of obsessive-compulsive disorder heterogeneity by allowing for open
      ended exploration of the obsessive-compulsive disorder experience and correlating
      identified subtypes with patient narratives. OBJECTIVE: We explored variations in
      patients' experience prior to, during and immediately after performing their
      compulsions. METHOD: Semi-structured interviews were conducted with 20 adults
      with obsessive-compulsive disorder, followed by inductive thematic analysis.
      Participant responses were not analyzed within the context of an existing
      theoretical framework, and themes were labeled descriptively. RESULTS: The
      previous dichotomy of 'anxiety' vs 'incompleteness' emerged organically during
      narrative analysis. In addition, we found that some individuals with obsessive
      compulsive disorder utilized their behaviors as a way to cope with stress and
      anxiety more generally. Other participants did not share this experience and
      denied finding any comfort in their obsessive-compulsive behaviors. The
      consequences of attentional difficulties were highlighted, with some participants
      describing how difficulty focusing on a task could influence the need for it to
      be repeated multiple times. CONCLUSIONS: The extent to which patients use
      obsessive-compulsive disorder as a coping mechanism is a relevant distinction
      with potential implications for treatment engagement. Patients may experience
      ambivalence about suppressing behaviors that they have come to rely upon for
      management of stress and anxiety, even if these behaviors represent symptoms of a
      psychiatric illness.

PMID- 25855686
TI  - Heart failure management in skilled nursing facilities: a scientific statement
      from the American Heart Association and the Heart Failure Society of America.

PMID- 25855687
TI  - The Short-Term Effect of Ketogenic Diet on Carotid Intima-Media Thickness and
      Elastic Properties of the Carotid Artery and the Aorta in Epileptic Children.
AB  - The aim of this prospective study is to investigate the effect of a 6-month-long
      ketogenic diet on carotid intima-media thickness, carotid artery, and aortic
      vascular functions. Thirty-eight drug-resistant epileptic patients who were being
      treated with ketogenic diet were enrolled. Fasting total cholesterol, high
      density lipoprotein, low-density lipoprotein, triglycerides, total cholesterol,
      and glucose concentrations were measured and echocardiography was performed in
      all patients before the beginning of ketogenic diet and at the sixth month of
      treatment. The body weight, height, body mass index, serum levels of
      triglyceride, total cholesterol, and low-density lipoprotein increased
      significantly at month 6 when compared to baseline values (P < .05). Carotid
      intima-media thickness, elastic properties of the aorta, and carotid artery did
      not change at the sixth month of therapy compared to baseline values. A 6-month
      long ketogenic diet has no effect on carotid intima-media thickness and elastic
      properties of the carotid artery and the aorta. 

PMID- 25855688
TI  - Assessment of Abilities and Comorbidities in Children With Cerebral Palsy.
AB  - This study examines major comorbidities in children with severe cerebral palsy
      and the feasibility of psychological tests for measuring abilities in a more
      impaired population. Eighty psychological evaluations of children with cerebral
      palsy aged 1.8 to 15.4 years (mean = 5.6) were analyzed. Major comorbid disorders
      were correlated with severity of motor disability. More than half of the cohort
      were diagnosed with severe cerebral palsy according to the Gross Motor Function
      Classification System. Multiple subtests were combined in order to assess the
      intellectual level. Normal intelligence was found in 22.5%, and 41.3% had
      moderate or severe intellectual impairment. Epilepsy occurred in 32.5% and
      attention-deficit hyperactivity disorder (ADHD) in 22.5%. Intellectual disability
      correlated with motor ability and with epilepsy. In a logistic regression model,
      epilepsy and motor ability score predicted 29.9% of IQ score variance.
      Intellectual impairment and epilepsy are common comorbidities. Subtests from
      different scales should be applied and interpreted with caution.

PMID- 25855689
TI  - Follow-up on long-term antiretroviral therapy for cats infected with feline
      immunodeficiency virus.
AB  - OBJECTIVES: Feline immunodeficiency virus (FIV) is a lentivirus that induces AIDS
      like disease in cats. Some of the antiretroviral drugs available to treat
      patients with HIV type 1 are used to treat FIV-infected cats; however,
      antiretroviral therapy (ART) is not used in cats as a long-term treatment. In
      this study, the effects of long-term ART were evaluated in domestic cats treated
      initially with the nucleoside transcriptase reverse inhibitor (NTRI) zidovudine
      (AZT) over a period ranging from 5-6 years, followed by a regimen of the NTRI
      lamivudine (3TC) plus AZT over 3 years. METHODS: Viral load, sequencing of pol
      (reverse transcriptase [RT]) region and CD4:CD8 lymphocyte ratio were evaluated
      during and after treatment. Untreated cats were evaluated as a control group.
      RESULTS: CD4:CD8 ratios were lower, and uncharacterized resistance mutations were
      found in the RT region in the group of treated cats. A slight increase in viral
      load was observed in some cats after discontinuing treatment. CONCLUSIONS AND
      RELEVANCE: The data strongly suggest that treated cats were resistant to therapy,
      and uncharacterized resistance mutations in the RT gene of FIV were selected for
      by AZT. Few studies have been conducted to evaluate the effect of long-term
      antiretroviral therapy in cats. To date, resistance mutations have not been
      described in vivo.

PMID- 25855690
TI  - Flexible explicit but rigid implicit learning in a visuomotor adaptation task.
AB  - There is mounting evidence for the idea that performance in a visuomotor rotation
      task can be supported by both implicit and explicit forms of learning. The
      implicit component of learning has been well characterized in previous
      experiments and is thought to arise from the adaptation of an internal model
      driven by sensorimotor prediction errors. However, the role of explicit learning
      is less clear, and previous investigations aimed at characterizing the explicit
      component have relied on indirect measures such as dual-task manipulations,
      posttests, and descriptive computational models. To address this problem, we
      developed a new method for directly assaying explicit learning by having
      participants verbally report their intended aiming direction on each trial. While
      our previous research employing this method has demonstrated the possibility of
      measuring explicit learning over the course of training, it was only tested over
      a limited scope of manipulations common to visuomotor rotation tasks. In the
      present study, we sought to better characterize explicit and implicit learning
      over a wider range of task conditions. We tested how explicit and implicit
      learning change as a function of the specific visual landmarks used to probe
      explicit learning, the number of training targets, and the size of the rotation.
      We found that explicit learning was remarkably flexible, responding appropriately
      to task demands. In contrast, implicit learning was strikingly rigid, with each
      task condition producing a similar degree of implicit learning. These results
      suggest that explicit learning is a fundamental component of motor learning and
      has been overlooked or conflated in previous visuomotor tasks. 

PMID- 25855691
TI  - Crossed motor innervation of the base of human tongue.
AB  - Muscle fibers of the genioglossus (GG) form the bulk of the muscle mass at the
      base of the tongue. The motor control of the tongue is critical for vocalization,
      feeding, and breathing. Our goal was to assess the patterns of motor innervation
      of GG single motor units (SMUs) in humans. Simultaneous monopolar recordings were
      obtained from four sites in the base of the tongue bilaterally at two antero
      posterior levels from 16 resting, awake, healthy adult males, who wore a face
      mask with airway pressure and airflow sensors. We analyzed 69 data segments in
      which at least one lead contained large action potentials generated by an SMU.
      Such potentials served as triggers for spike-triggered averaging (STA) of signals
      recorded from the other three sites. Spontaneous activity of the SMUs was
      classified as inspiratory modulated, expiratory modulated, or tonic. Consistent
      with the antero-posterior orientation of GG fibers, 44 STAs (77%) recorded
      ipsilateral to the trigger yielded sharp action potentials with a median
      amplitude of 52 MUV [interquartile range (IQR): 25-190] that were time shifted
      relative to the trigger by about 1 ms. Notably, 48% of recordings on the side
      opposite to the trigger also yielded sharp action potentials. Of those, 17 (29%)
      had a median amplitude of 63 MUV (IQR: 39-96), and most were generated by tonic
      SMUs. Thus a considerable proportion of GG muscle fibers receive a crossed motor
      innervation. Crossed innervation may help ensure symmetry and stability of tongue
      position and movements under normal conditions and following injury or
      degenerative changes affecting the tongue. 

PMID- 25855692
TI  - Deflection of a vibrissa leads to a gradient of strain across mechanoreceptors in
      a mystacial follicle.
AB  - Rodents use their vibrissae to detect and discriminate tactile features during
      active exploration. The site of mechanical transduction in the vibrissa
      sensorimotor system is the follicle sinus complex and its associated vibrissa. We
      study the mechanics within the ring sinus (RS) of the follicle in an ex vivo
      preparation of the mouse mystacial pad. The sinus region has a relatively dense
      representation of Merkel mechanoreceptors and longitudinal lanceolate endings.
      Two-photon laser-scanning microscopy was used to visualize labeled cell nuclei in
      an ~ 100-nl vol before and after passive deflection of a vibrissa, which results
      in localized displacements of the mechanoreceptor cells, primarily in the radial
      and polar directions about the vibrissa. These displacements are used to compute
      the strain field across the follicle in response to the deflection. We observe
      compression in the lower region of the RS, whereas dilation, with lower
      magnitude, occurs in the upper region, with volumetric strain DeltaV/V ~ 0.01 for
      a 10 degrees  deflection. The extrapolated strain for a 0.1 degrees  deflection,
      the minimum angle that is reported to initiate a spike by primary neurons,
      corresponds to the minimum strain that activates Piezo2 mechanoreceptor channels.

PMID- 25855693
TI  - Adaptation and adaptation transfer characteristics of five different saccade
      types in the monkey.
AB  - Shifts in the direction of gaze are accomplished by different kinds of saccades,
      which are elicited under different circumstances. Saccade types include targeting
      saccades to simple jumping targets, delayed saccades to visible targets after a
      waiting period, memory-guided (MG) saccades to remembered target locations,
      scanning saccades to stationary target arrays, and express saccades after very
      short latencies. Studies of human cases and neurophysiological experiments in
      monkeys suggest that separate pathways, which converge on a common locus that
      provides the motor command, generate these different types of saccade. When
      behavioral manipulations in humans cause targeting saccades to have persistent
      dysmetrias as might occur naturally from growth, aging, and injury, they
      gradually adapt to reduce the dysmetria. Although results differ slightly between
      laboratories, this adaptation generalizes or transfers to all the other saccade
      types mentioned above. Also, when one of the other types of saccade undergoes
      adaptation, it often transfers to another saccade type. Similar adaptation and
      transfer experiments, which allow inferences to be drawn about the site(s) of
      adaptation for different saccade types, have yet to be done in monkeys. Here we
      show that simian targeting and MG saccades adapt more than express, scanning, and
      delayed saccades. Adaptation of targeting saccades transfers to all the other
      saccade types. However, the adaptation of MG saccades transfers only to delayed
      saccades. These data suggest that adaptation of simian targeting saccades occurs
      on the pathway common to all saccade types. In contrast, only the delayed saccade
      command passes through the adaptation site of the MG saccade. 

PMID- 25855694
TI  - Femoral artery ligation increases the responses of thin-fiber muscle afferents to
      contraction.
AB  - Previous evidence has shown that ligating the femoral artery for 72 h resulted in
      an exaggerated exercise pressor reflex. To provide electrophysiological evidence
      for this finding, we examined in decerebrated rats whose femoral arteries were
      either freely perfused or ligated for 72 h the responses of thin-fiber (i.e.,
      groups III and IV) afferents to static contraction of the hindlimb muscles. We
      found that contraction increased the combined activity of group III and IV
      afferents in both freely perfused (n = 29; baseline: 0.3 +/- 0.1 imp/s,
      contraction: 0.8 +/- 0.2 imp/s; P < 0.05) and ligated rats (n = 28; baseline: 0.4
      +/- 0.1 imp/s, contraction: 1.4 +/- 0.1 imp/s; P < 0.05). Most importantly, the
      contraction-induced increase in afferent activity was greater in ligated rats
      than it was in freely perfused rats (P = 0.005). In addition, the responses of
      group III afferents to contraction in ligated rats (n = 15; baseline 0.3 +/- 0.1
      imp/s, contraction 1.5 +/- 0.2 imp/s) were greater (P = 0.024) than the responses
      to contraction in freely perfused rats (n = 18; baseline 0.3 +/- 0.1 imp/s,
      contraction 0.9 +/- 0.2 imp/s). Likewise, the responses of group IV afferents to
      contraction in ligated rats (n = 13; baseline 0.5 +/- 0.1 imp/s, contraction 1.3
      +/- 0.2 imp/s) were greater (P = 0.048) than the responses of group IV afferents
      in freely perfused rats (n = 11; baseline 0.3 +/- 0.1 imp/s, contraction 0.6 +/-
      0.2 imp/s). We conclude that both group III and IV afferents contribute to the
      exaggeration of the exercise pressor reflex induced by femoral artery ligation. 

PMID- 25855695
TI  - Activity-dependent differences in function between proximal and distal Schaffer
      collaterals.
AB  - Axon conduction fidelity is important for signal transmission and has been
      studied in various axons, including the Schaffer collateral axons of the
      hippocampus. Previously, we reported that high-frequency stimulation (HFS)
      depresses Schaffer collateral excitability when assessed by whole-cell recordings
      from CA3 pyramidal cells but induces biphasic excitability changes (increase
      followed by decrease) in extracellular recordings of CA1 fiber volleys. Here, we
      examined responses from proximal (whole-cell or field-potential recordings from
      CA3 pyramidal cell somata) and distal (field-potential recordings from CA1
      stratum radiatum) portions of the Schaffer collaterals during HFS and burst
      stimulation in hippocampal slices. Whole-cell and dual-field-potential recordings
      using 10-100-Hz HFS revealed frequency-dependent changes like those previously
      described, with higher frequencies producing more drastic changes. Dual-field
      potential recordings revealed substantial differences in the response to HFS
      between proximal and distal regions of the Schaffer collaterals, with proximal
      axons depressing more strongly and only distal axons showing an initial
      excitability increase. Because CA3 pyramidal neurons normally fire in short
      bursts rather than long high-frequency trains, we repeated the dual recordings
      using 100-1,000-ms interval burst stimulation. Burst stimulation produced changes
      similar to those during HFS, with shorter intervals causing more drastic changes
      and substantial differences observed between proximal and distal axons. We
      suggest that functional differences between proximal and distal Schaffer
      collaterals may allow selective filtering of nonphysiological activity while
      maximizing successful conduction of physiological activity throughout an
      extensive axonal arbor. 

PMID- 25855696
TI  - Different pools of glutamate receptors mediate sensitivity to ambient glutamate
      in the cochlear nucleus.
AB  - Ambient glutamate plays an important role in pathological conditions, such as
      stroke, but its role during normal activity is not clear. In addition, it is not
      clear how ambient glutamate acts on glutamate receptors with varying affinities
      or subcellular localizations. To address this, we studied "endbulb of Held"
      synapses, which are formed by auditory nerve fibers onto bushy cells (BCs) in the
      anteroventral cochlear nucleus. When ambient glutamate was increased by applying
      the glutamate reuptake inhibitor TFB-TBOA, BCs depolarized as a result of
      activation of N-methyl-D-aspartate receptors (NMDARs) and group I metabotropic
      glutamate receptors (mGluRs). Application of antagonists against NMDARs (in 0
      Mg(2+)) or mGluRs caused hyperpolarization, indicating that these receptors were
      bound by a tonic source of glutamate. AMPA receptors did not show these effects,
      consistent with their lower glutamate affinity. We also evaluated the subcellular
      localization of the receptors activated by ambient glutamate. The mGluRs were not
      activated by synaptic stimulation and thus appear to be exclusively
      extrasynaptic. By contrast, NMDARs in both synaptic and extrasynaptic
      compartments were activated by ambient glutamate, as shown using the use
      dependent antagonist MK-801. Levels of ambient glutamate appeared to be regulated
      in a spike-independent manner, and glia likely play a major role. These low
      levels of ambient glutamate likely have functional consequences, as even low
      concentrations of TBOA caused significant increases in BC spiking following
      synaptic stimulation. These results indicate that normal resting potential
      appears to be poised in the region of maximal sensitivity to small changes in
      ambient glutamate.

PMID- 25855697
TI  - Interactions between rostral and caudal cortical motor areas in the rat.
AB  - In rats, forelimb movements can be evoked from two distinct cortical regions, the
      rostral (RFA) and the caudal (CFA) forelimb areas. RFA and CFA have numerous
      reciprocal connections, and their projections reach several common targets, which
      allows them to interact at multiple levels of the motor axis. Lesions affecting
      these areas result in profound and persistent deficits, supporting their
      essential role for the production of arm and hand movements. Whereas rats are
      widely used to study motor control and recovery following lesions, little is
      known as to how cortical motor areas in this model interact to generate
      movements. To study interactions between RFA and CFA, we used paired-pulse
      protocols with intracortical microstimulation techniques (ICMS). A conditioning
      stimulus (C) in RFA was applied simultaneously, or before a test stimulus (T) in
      CFA. The impact of RFA conditioning on CFA outputs was quantified by recording
      electromyographic signals (EMG) signals from the contralateral arm muscles. We
      found that stimulation of RFA substantially modulates the intensity of CFA
      outputs while only mildly affecting the latency. In general, the effect of RFA
      conditioning changed from predominantly facilitatory to inhibitory with
      increasing delays between the C and the T stimulus. However, inspection of
      individual cortical sites revealed that RFA has a wide range of influence on CFA
      outputs with each interstimulation delay we used. Our results show that RFA has
      powerful and complex modulatory effects on CFA outputs that can allow it to play
      a major role in the cortical control of forelimb movements. 

PMID- 25855698
TI  - A unifying principle underlying the extracellular field potential spectral
      responses in the human cortex.
AB  - Electrophysiological mass potentials show complex spectral changes upon neuronal
      activation. However, it is unknown to what extent these complex band-limited
      changes are interrelated or, alternatively, reflect separate neuronal processes.
      To address this question, intracranial electrocorticograms (ECoG) responses were
      recorded in patients engaged in visuomotor tasks. We found that in the 10- to 100
      Hz frequency range there was a significant reduction in the exponent chi of the
      1/f(chi) component of the spectrum associated with neuronal activation. In a
      minority of electrodes showing particularly high activations the exponent
      reduction was associated with specific band-limited power modulations: emergence
      of a high gamma (80-100 Hz) and a decrease in the alpha (9-12 Hz) peaks.
      Importantly, the peaks' height was correlated with the 1/f(chi) exponent on
      activation. Control simulation ruled out the possibility that the change in
      1/f(chi) exponent was a consequence of the analysis procedure. These results
      reveal a new global, cross-frequency (10-100 Hz) neuronal process reflected in a
      significant reduction of the power spectrum slope of the ECoG signal. 

PMID- 25855699
TI  - Two ways to save a newly learned motor pattern.
AB  - Savings, or faster relearning after initial learning, demonstrates humans'
      remarkable ability to retain learned movements amid changing environments. This
      is important within the context of locomotion, as the ability of the nervous
      system to "remember" how to walk in specific environments enables us to navigate
      changing terrains and progressively improve gait patterns with rehabilitation.
      Here, we used a split-belt treadmill to study precisely how people save newly
      learned walking patterns. In Experiment 1, we investigated savings by
      systematically varying the learning and unlearning environments. Savings was
      predominantly influenced by 1) previous exposure to similar abrupt changes in the
      environment and 2) the amount of exposure to the new environment. Relearning was
      fastest when these two factors coincided, and we did not observe savings after
      the environment was introduced gradually during initial learning. In Experiment
      2, we then studied whether people store explicit information about different
      walking environments that mirrors savings of a new walking pattern. Like savings,
      we found that previous exposure to abrupt changes in the environment also drove
      the ability to recall a previously experienced walking environment accurately.
      Crucially, the information recalled was extrinsic information about the learning
      environment (i.e., treadmill speeds) and not intrinsic information about the
      walking pattern itself. We conclude that simply learning a new walking pattern is
      not enough for long-term savings; rather, savings of a learned walking pattern
      involves recall of the environment or extended training at the learned state. 

PMID- 25855700
TI  - Closed-loop, ultraprecise, automated craniotomies.
AB  - A large array of neuroscientific techniques, including in vivo electrophysiology,
      two-photon imaging, optogenetics, lesions, and microdialysis, require access to
      the brain through the skull. Ideally, the necessary craniotomies could be
      performed in a repeatable and automated fashion, without damaging the underlying
      brain tissue. Here we report that when drilling through the skull a stereotypical
      increase in conductance can be observed when the drill bit passes through the
      skull base. We present an architecture for a robotic device that can perform this
      algorithm, along with two implementations--one based on homebuilt hardware and
      one based on commercially available hardware--that can automatically detect such
      changes and create large numbers of precise craniotomies, even in a single skull.
      We also show that this technique can be adapted to automatically drill cranial
      windows several millimeters in diameter. Such robots will not only be useful for
      helping neuroscientists perform both small and large craniotomies more reliably
      but can also be used to create precisely aligned arrays of craniotomies with
      stereotaxic registration to standard brain atlases that would be difficult to
      drill by hand.

PMID- 25855701
TI  - Design and Evaluation of an Electronic Override Mechanism for Medication Alerts
      to Facilitate Communication Between Prescribers and Pharmacists.
AB  - BACKGROUND: Computerized medication alerts can often be bypassed by entering an
      override rationale, but prescribers' override reasons are frequently ambiguous to
      pharmacists who review orders. OBJECTIVE: To develop and evaluate a new override
      mechanism for adverse reaction and drug-drug interaction alerts. We hypothesized
      that the new mechanism would improve usability for prescribers and increase the
      clinical appropriateness of override reasons. METHODS: A counterbalanced,
      crossover study was conducted with 20 prescribers in a simulated prescribing
      environment. We modified the override mechanism timing, navigation, and text
      entry. Instead of free-text entry, the new mechanism presented prescribers with a
      predefined set of override reasons. We assessed usability (learnability,
      perceived efficiency, and usability errors) and used a priori criteria to
      evaluate the clinical appropriateness of override reasons entered. RESULTS:
      Prescribers rated the new mechanism as more efficient (Wilcoxon signed-rank test,
      P = 0.032). When first using the new design, 5 prescribers had difficulty finding
      the new mechanism, and 3 interpreted the navigation to mean that the alert could
      not be overridden. The number of appropriate override reasons significantly
      increased with the new mechanism compared with the original mechanism (median
      change of 3.0; interquartile range = 3.0; P < 0.0001). CONCLUSIONS: When
      prescribers were given a menu-based choice for override reasons, clinical
      appropriateness of these reasons significantly improved. Further enhancements are
      necessary, but this study is an important first step toward a more standardized
      menu of override choices. Findings may be used to improve communication through e
      prescribing systems between prescribers and pharmacists.

PMID- 25855702
TI  - Direct-acting oral anticoagulants as emerging treatment options for heparin
      induced thrombocytopenia.
AB  - OBJECTIVE: To review the evidence for the use of the direct-acting oral
      anticoagulants (DOACs) in adult patients with heparin-induced thrombocytopenia
      (HIT). DATA SOURCE: A PubMed search (1950-February 2015) was collected using the
      terms heparin-induced thrombocytopenia, with dabigatran, rivaroxaban, or
      apixaban, or heparin-induced thrombocytopenia and target-specific anticoagulants,
      or heparin-induced thrombocytopenia and direct-acting oral anticoagulants, or
      heparin-induced thrombocytopenia and new oral anticoagulants. STUDY SELECTION AND
      DATA EXTRACTION: All English-language articles were reviewed for inclusion. The
      references of included articles were reviewed for additional data. DATA
      SYNTHESIS: HIT is an immune-mediated, prothrombotic adverse reaction that
      requires not only discontinuation of heparin but also initiation of an
      alternative nonheparin anticoagulant to counter the effects of the autoimmune
      cascade. Pharmacotherapeutic management with argatroban is unpredictable and
      problematic. The DOACs display predictable pharmacokinetic and pharmacodynamic
      profiles and exhibit no interaction with platelet factor 4. Currently, the DOACs
      are approved by the Food and Drug Administration for venous thromboembolism, yet
      have limited evidence in both in vitro and clinical HIT studies. CONCLUSIONS:
      Though dabigatran, rivaroxaban, and apixaban have been used in case reports,
      currently data are not yet sufficient to recommend clinical use of these agents
      in the management of HIT. Future trial results may further substantiate
      management of HIT with use of the DOACs.

PMID- 25855703
TI  - Clinical and Economic Impact of Empirical Extended-Infusion Piperacillin
      Tazobactam in a Community Medical Center.
AB  - BACKGROUND: Current medical center practice allows for the automatic conversion
      of all piperacillin/tazobactam orders from intermittent to extended infusion
      (EI). OBJECTIVE: To compare the clinical and cost impact of empirical extended
      infusion piperacillin/tazobactam. METHODS: All consecutive patients treated with
      piperacillin/tazobactam for >48 hours were reviewed for inclusion. Patients were
      stratified into 2 groups: (1) traditional infusion (TI), preprotocol
      implementation, and (2) EI, postprotocol implementation. Patient demographics and
      primary and secondary diagnoses were extracted from the hospital discharge
      database. All patients were assessed for the primary end point of all cause 14
      day in-hospital mortality. Secondary outcomes included length of hospital stay,
      duration of antibiotic therapy, cost per treatment course, and occurrence of
      Clostridium difficile infection. RESULTS: A total of 2150 patients were included
      (EI = 632; TI = 1518). After adjusting for comorbidity, length of stay, and age,
      14-day in-hospital mortality was similar between groups (odds ratio = 1.16; 95%
      CI = 0.85-1.58; P = 0.37). Length of stay was similar between the EI group versus
      TI (mean +/- SD: 12.5 +/- 9.58 days vs 11.8 +/- 9.58 days, respectively; P =
      0.10) after adjusting for age and Chalson-Deyo comorbidity index. Total cost per
      treatment course was reduced in the EI group by 13% compared with the TI group
      ($565.90 +/- $257.70 vs $648.30 +/- $349.20, respectively; P < 0.0001).
      CONCLUSION: Automatic substitution of EI for TI piperacillin/tazobactam is safe
      and associated with significant cost savings. EI piperacillin/tazobactam was not
      associated with a reduction in mortality or length of stay.

PMID- 25855704
TI  - Edoxaban, a Novel Oral Factor Xa Inhibitor.
AB  - OBJECTIVE: To evaluate the current literature and potential clinical role of
      edoxaban (Savaysa) for stroke prevention in nonvalvular atrial fibrillation
      (NVAF) and treatment of deep-vein thrombosis and pulmonary embolism. DATA
      SOURCES: A PubMed and Cochrane Central Register of Controlled trials search was
      conducted in February 2015 using the search terms edoxaban (ordu-176b) and atrial
      fibrillation, deep vein thrombosis, pulmonary embolism, or venous
      thromboembolism. Bibliographies of all retrieved articles were reviewed. All
      references included were published between 1998 and 2015. STUDY SELECTION/DATA
      EXTRACTION: All studies that included humans and contained data describing the
      use of edoxaban for either stroke prevention in patients with NVAF or the
      treatment of venous thromboembolism (VTE) were reviewed. DATA SYNTHESIS: Edoxaban
      is a target-specific oral anticoagulant, specifically a factor Xa inhibitor. It
      has been studied in 4 major randomized controlled trials for the prevention of
      stroke and systemic embolism in patients with NVAF. One randomized controlled
      trial was conducted for the treatment of VTE. Edoxaban demonstrated
      noninferiority of the primary efficacy end point compared with warfarin for both
      approved indications. The most common adverse effect is bleeding, similar to
      other anticoagulants. A dosing limitation exists related to patients treated for
      NVAF with creatinine clearance >95 mL/min; these patients experienced decreased
      efficacy. CONCLUSIONS: Edoxaban is a safe and effective anticoagulant to reduce
      the risk of stroke in patients with NVAF and for the treatment of VTE.

PMID- 25855705
TI  - Heparin-Calibrated Chromogenic Anti-Xa Activity Measurements in Patients
      Receiving Rivaroxaban: Can This Test Be Used to Quantify Drug Level?
AB  - BACKGROUND: Determination of plasma rivaroxaban concentration may be necessary in
      certain clinical situations. Rivaroxaban concentration can be accurately and
      rapidly determined using a chromogenic anti-activated factor X (factor Xa) assay
      with specific drug calibrator material. However, there are currently no Food and
      Drug Administration (FDA)-approved rivaroxaban calibrators available in the
      United States. OBJECTIVE: To determine whether FDA-approved commercial kits for
      measuring heparin anti-factor Xa activity can be used to assess rivaroxaban
      concentrations when calibrated for unfractionated heparin or low-molecular-weight
      heparins. METHODS: Trough and peak samples were taken from 30 patients taking
      rivaroxaban as part of their routine care for atrial fibrillation or venous
      thromboembolism. The samples were tested using 3 different FDA-approved
      commercial kits for measuring heparin anti-factor Xa activity. RESULTS: There was
      acceptable correlation between rivaroxaban levels and heparin anti-factor Xa
      activity using Berichrom and COAMATIC heparin kits. The STA liquid heparin method
      was the most sensitive to presence of rivaroxaban. CONCLUSION: This study
      demonstrates a strong correlation, but variability between kits, for assessing
      rivaroxaban concentrations using heparin anti-factor Xa assays. The extent of the
      heparin calibration curve significantly limits the measurable rivaroxaban range,
      and this application may be useful only for trough samples. The STA liquid
      heparin, being exquisitely sensitive to rivaroxaban, may be suitable for ruling
      out presence of the drug. The routine use of heparin-calibrated anti-factor Xa
      assays to quantify rivaroxaban is not advocated, and when applied, it must be
      used with caution and limitations clearly understood.

PMID- 25855706
TI  - Re: Pan-Canadian study of mammography screening and mortality from breast cancer.

PMID- 25855708
TI  - Breast cancer prevention in the era of precision medicine.

PMID- 25855710
TI  - Commentary: The information of conformation.

PMID- 25855709
TI  - Using linked educational attainment data to reduce bias due to missing outcome
      data in estimates of the association between the duration of breastfeeding and IQ
      at 15 years.
AB  - BACKGROUND: Most epidemiological studies have missing information, leading to
      reduced power and potential bias. Estimates of exposure-outcome associations will
      generally be biased if the outcome variable is missing not at random (MNAR).
      Linkage to administrative data containing a proxy for the missing study outcome
      allows assessment of whether this outcome is MNAR and the evaluation of bias. We
      examined this in relation to the association between infant breastfeeding and IQ
      at 15 years, where a proxy for IQ was available through linkage to school
      attainment data. METHODS: Subjects were those who enrolled in the Avon
      Longitudinal Study of Parents and Children in 1990-91 (n = 13 795), of whom 5023
      had IQ measured at age 15. For those with missing IQ, 7030 (79%) had information
      on educational attainment at age 16 obtained through linkage to the National
      Pupil Database. The association between duration of breastfeeding and IQ was
      estimated using a complete case analysis, multiple imputation and inverse
      probability-of-missingness weighting; these estimates were then compared with
      those derived from analyses informed by the linkage. RESULTS: IQ at 15 was MNAR
      individuals with higher attainment were less likely to have missing IQ data, even
      after adjusting for socio-demographic factors. All the approaches underestimated
      the association between breastfeeding and IQ compared with analyses informed by
      linkage. CONCLUSIONS: Linkage to administrative data containing a proxy for the
      outcome variable allows the MNAR assumption to be tested and more efficient
      analyses to be performed. Under certain circumstances, this may produce unbiased
      results.

PMID- 25855711
TI  - Commentary: Age and frailty-not quite the same thing.

PMID- 25855712
TI  - LDL cholesterol still a problem in old age? A Mendelian randomization study.
AB  - BACKGROUND: Observational studies in older subjects have shown no or inverse
      associations between cholesterol levels and mortality. However, in old age plasma
      low-density lipoprotein cholesterol (LDL-C) may not reflect the lifetime level
      due to reverse causality, and hence the risk may be underestimated. In the
      current study, we used an LDL genetic risk score (GRS) to overcome this problem.
      METHODS: A weighted GRS was created using 51 single nucleotide polymorphisms
      associated with LDL-C levels. The LDL GRS was calculated in three Dutch cohorts:
      the Leiden Longevity Study (LLS) (n = 3270), the Leiden 85-plus study (n = 316)
      and the Rotterdam Study (n = 4035). We assessed the association between the LDL
      GRS and LDL-C levels, chronological age, familial longevity and mortality.
      RESULTS: Up to 90 years of age, in each age stratum individuals with high LDL GRS
      had higher LDL-C levels (P = 0.010 to P = 1.1 x 10(-16)). The frequency of LDL
      increasing alleles decreased with increasing age [beta = -0.021 (SE = 0.01) per
      year, P = 0.018]. Moreover, individuals with a genetic predisposition for
      longevity had significantly lower LDL GRS compared with age-matched individuals
      of the general population [LLS nonagenarians vs > 90 years: beta = 0.73 (SE =
      0.33), P = 0.029, LLS offspring vs partners: beta = 0.66 (SE = 0.23), P = 0.005].
      In longitudinal analysis, high GRS was associated with increased all-cause
      mortality in individuals > 90 years, with a 13% increased risk in individuals
      with the highest LDL GRS (P-trend = 0.043). CONCLUSION: Results of the current
      study indicate that a genetic predisposition to high LDL-C levels contributes to
      mortality throughout life, including in the oldest old, and a beneficial LDL
      genetic risk profile is associated with familial longevity.

PMID- 25855713
TI  - Commentary: A conceptual revolution limited by disciplinary division.

PMID- 25855714
TI  - Commentary: Far-reaching hypothesis or a step too far: the inheritance of
      acquired characteristics.

PMID- 25855715
TI  - Commentary: Reflections on: Jablonka E, Lamb MJ. The inheritance of acquired
      epigenetic variations.

PMID- 25855707
TI  - Prediction of breast cancer risk based on profiling with common genetic variants.
AB  - BACKGROUND: Data for multiple common susceptibility alleles for breast cancer may
      be combined to identify women at different levels of breast cancer risk. Such
      stratification could guide preventive and screening strategies. However,
      empirical evidence for genetic risk stratification is lacking. METHODS: We
      investigated the value of using 77 breast cancer-associated single nucleotide
      polymorphisms (SNPs) for risk stratification, in a study of 33 673 breast cancer
      cases and 33 381 control women of European origin. We tested all possible pair
      wise multiplicative interactions and constructed a 77-SNP polygenic risk score
      (PRS) for breast cancer overall and by estrogen receptor (ER) status. Absolute
      risks of breast cancer by PRS were derived from relative risk estimates and UK
      incidence and mortality rates. RESULTS: There was no strong evidence for
      departure from a multiplicative model for any SNP pair. Women in the highest 1%
      of the PRS had a three-fold increased risk of developing breast cancer compared
      with women in the middle quintile (odds ratio [OR] = 3.36, 95% confidence
      interval [CI] = 2.95 to 3.83). The ORs for ER-positive and ER-negative disease
      were 3.73 (95% CI = 3.24 to 4.30) and 2.80 (95% CI = 2.26 to 3.46), respectively.
      Lifetime risk of breast cancer for women in the lowest and highest quintiles of
      the PRS were 5.2% and 16.6% for a woman without family history, and 8.6% and
      24.4% for a woman with a first-degree family history of breast cancer.
      CONCLUSIONS: The PRS stratifies breast cancer risk in women both with and without
      a family history of breast cancer. The observed level of risk discrimination
      could inform targeted screening and prevention strategies. Further discrimination
      may be achievable through combining the PRS with lifestyle/environmental factors,
      although these were not considered in this report.

PMID- 25855717
TI  - The inheritance of acquired epigenetic variations.
AB  - There is evidence that the functional history of a gene in one generation can
      influence its expression in the next. In somatic cells, changes in gene activity
      are frequently associated with changes in the pattern of methylation of the
      cytosines in DNA; these methylation patterns are stably inherited. Recent work
      suggests that information about patterns of methylation and other epigenetic
      states can also be transmitted from parents to offspring. This evidence is the
      basis of a model for the inheritance of acquired epigenetic variations. According
      to the model, an environmental stimulus can induce heritable chromatin
      modifications which are very specific and predictable, and might result in an
      adaptive response to the stimulus. This type of response probably has most
      significance for adaptive evolution in organisms such as fungi and plants, which
      lack distinct segregation of the soma and germ line. However, in all organisms,
      the accumulation of specific and random chromatin modifications in the germ line
      may be important in speciation, because these modifications could lead to
      reproductive isolation between populations. Heritable chromatin variations may
      also alter the frequency and distribution of classical mutations and meiotic
      recombination. Therefore, inherited epigenetic changes in the structure of
      chromatin can influence neo-Darwinian evolution as well as cause a type of
      "Lamarckian" inheritance. 

PMID- 25855716
TI  - Exposure to aflatoxin B1 in utero is associated with DNA methylation in white
      blood cells of infants in The Gambia.
AB  - BACKGROUND: Exposure to environmental toxins during embryonic development may
      lead to epigenetic changes that influence disease risk in later life. Aflatoxin
      is a contaminant of staple foods in sub-Saharan Africa, is a known human liver
      carcinogen and has been associated with stunting in infants. METHODS: We have
      measured aflatoxin exposure in 115 pregnant women in The Gambia and examined the
      DNA methylation status of white blood cells from their infants at 2-8 months old
      (mean 3.6 +/- 0.9). Aflatoxin exposure in women was assessed using an ELISA
      method to measure aflatoxin albumin (AF-alb) adducts in plasma taken at 1-16
      weeks of pregnancy. Genome-wide DNA methylation of infant white blood cells was
      measured using the Illumina Infinium HumanMethylation450beadchip. RESULTS: AF-alb
      levels ranged from 3.9 to 458.4 pg/mg albumin. We found that aflatoxin exposure
      in the mothers was associated to DNA methylation in their infants for 71 CpG
      sites (false discovery rate < 0.05), with an average effect size of 1.7% change
      in methylation. Aflatoxin-associated differential methylation was observed in
      growth factor genes such as FGF12 and IGF1, and immune-related genes such as
      CCL28, TLR2 and TGFBI. Moreover, one aflatoxin-associated methylation region
      (corresponding to the miR-4520b locus) was identified. CONCLUSIONS: This study
      shows that maternal exposure to aflatoxin during the early stages of pregnancy is
      associated with differential DNA methylation patterns of infants, including in
      genes related to growth and immune function. This reinforces the need for
      interventions to reduce aflatoxin exposure, especially during critical periods of
      fetal and infant development.

PMID- 25855718
TI  - Commentary: The beginning of the end of the 'modern synthesis'? Commentary on
      Jablonka E, Lamb MJ. The inheritance of acquired epigenetic variations.

PMID- 25855719
TI  - Debating interaction: the history, and an explanation.

PMID- 25855721
TI  - Some of the complexities involved in gene-environment interplay.

PMID- 25855720
TI  - Maternal pre-pregnancy BMI and gestational weight gain, offspring DNA methylation
      and later offspring adiposity: findings from the Avon Longitudinal Study of
      Parents and Children.
AB  - BACKGROUND: Evidence suggests that in utero exposure to undernutrition and
      overnutrition might affect adiposity in later life. Epigenetic modification is
      suggested as a plausible mediating mechanism. METHODS: We used multivariable
      linear regression and a negative control design to examine offspring epigenome
      wide DNA methylation in relation to maternal and offspring adiposity in 1018
      participants. RESULTS: Compared with neonatal offspring of normal weight mothers,
      28 and 1621 CpG sites were differentially methylated in offspring of obese and
      underweight mothers, respectively [false discovert rate (FDR)-corrected P-value <
      0.05), with no overlap in the sites that maternal obesity and underweight relate
      to. A positive association, where higher methylation is associated with a body
      mass index (BMI) outside the normal range, was seen at 78.6% of the sites
      associated with obesity and 87.9% of the sites associated with underweight.
      Associations of maternal obesity with offspring methylation were stronger than
      associations of paternal obesity, supporting an intrauterine mechanism. There
      were no consistent associations of gestational weight gain with offspring DNA
      methylation. In general, sites that were hypermethylated in association with
      maternal obesity or hypomethylated in association with maternal underweight
      tended to be positively associated with offspring adiposity, and sites
      hypomethylated in association with maternal obesity or hypermethylated in
      association with maternal underweight tended to be inversely associated with
      offspring adiposity. CONCLUSIONS: Our data suggest that both maternal obesity
      and, to a larger degree, underweight affect the neonatal epigenome via an
      intrauterine mechanism, but weight gain during pregnancy has little effect. We
      found some evidence that associations of maternal underweight with lower
      offspring adiposity and maternal obesity with greater offspring adiposity may be
      mediated via increased DNA methylation.

PMID- 25855722
TI  - Sexual offending runs in families: A 37-year nationwide study.
AB  - BACKGROUND: Sexual crime is an important public health concern. The possible
      causes of sexual aggression, however, remain uncertain. METHODS: We examined
      familial aggregation and the contribution of genetic and environmental factors to
      sexual crime by linking longitudinal, nationwide Swedish crime and
      multigenerational family registers. We included all men convicted of any sexual
      offence (N = 21,566), specifically rape of an adult (N = 6131) and child
      molestation (N = 4465), from 1973 to 2009. Sexual crime rates among fathers and
      brothers of sexual offenders were compared with corresponding rates in fathers
      and brothers of age-matched population control men without sexual crime
      convictions. We also modelled the relative influence of genetic and environmental
      factors to the liability of sexual offending. RESULTS: We found strong familial
      aggregation of sexual crime [odds ratio (OR) = 5.1, 95% confidence interval (CI)
      = 4.5-5.9] among full brothers of convicted sexual offenders. Familial
      aggregation was lower in father-son dyads (OR = 3.7, 95% CI = 3.2-4.4) among
      paternal half-brothers (OR = 2.1, 95% CI = 1.5-2.9) and maternal half-brothers
      (OR = 1.7, 95% CI = 1.2-2.4). Statistical modelling of the strength and patterns
      of familial aggregation suggested that genetic factors (40%) and non-shared
      environmental factors (58%) explained the liability to offend sexually more than
      shared environmental influences (2%). Further, genetic effects tended to be
      weaker for rape of an adult (19%) than for child molestation (46%). CONCLUSIONS:
      We report strong evidence of familial clustering of sexual offending, primarily
      accounted for by genes rather than shared environmental influences. Future
      research should possibly test the effectiveness of selective prevention efforts
      for male first-degree relatives of sexually aggressive individuals, and consider
      familial risk in sexual violence risk assessment.

PMID- 25855724
TI  - Crossing the 'explanatory divide': a bridge to nowhere?

PMID- 25855723
TI  - Understanding the candidate gene * environment interaction debate:
      epistemological or evidential divide?

PMID- 25855726
TI  - Thyroid dysfunction, thyroid hormone replacement and colorectal cancer risk.
AB  - BACKGROUND: Current screening guidelines for colorectal cancer (CRC) do not
      consider thyroid dysfunction as a risk factor for disease development. We sought
      to determine the risk of developing CRC in patients with thyroid dysfunction,
      with and without thyroid hormone replacement (THR). METHODS: We conducted a
      nested case-control study using a large population-based medical records database
      from the United Kingdom. Study case patients were defined as those with any
      medical code of CRC. Subjects with familial colorectal cancer syndromes or
      inflammatory bowel disease (IBD) were excluded. For every case patient, four
      eligible control patients matched on age, sex, practice site, and duration of
      follow-up before index date were selected using incidence density sampling.
      Exposure was THR therapy before index date. We further divided the THR unexposed
      group into patients with hypothyroidism (TSH > 4 mg/dl), patients with
      hyperthyroidism (TSH < 0.4 mg/dl), and subjects without documented thyroid
      abnormality. The adjusted odds ratios (ORs) and 95% confidence intervals (CIs)
      for CRC were estimated using conditional logistic regression. All statistical
      tests were two-sided. RESULTS: We identified 20990 CRC patients and 82054 control
      patients. The adjusted odds ratio for CRC associated with THR was 0.88 (95% CI =
      0.79 to 0.99, P = .03) and 0.68 (95% CI = 0.55 to 0.83, P < .001) for treatment
      initiated five to 10 years and more than 10 years before index date,
      respectively. This protective association increased with cumulative duration of
      therapy. In contrast, hyperthyroidism (adjusted OR = 1.21, 95% CI = 1.08 to 1.36,
      P = .001) or untreated hypothyroidism (adjusted OR = 1.16, 95% CI = 1.08 to 1.24,
      P < .001) were associated with increased risk of CRC. CONCLUSION: Long-term THR
      is associated with a decreased risk of CRC. Hyperthyroidism and untreated
      hypothyroidism are associated with modestly elevated risk of CRC.

PMID- 25855725
TI  - Role of cannabinoid receptor CB2 in HER2 pro-oncogenic signaling in breast
      cancer.
AB  - BACKGROUND: Pharmacological activation of cannabinoid receptors elicits
      antitumoral responses in different cancer models. However, the biological role of
      these receptors in tumor physio-pathology is still unknown. METHODS: We analyzed
      CB2 cannabinoid receptor protein expression in two series of 166 and 483 breast
      tumor samples operated in the University Hospitals of Kiel, Tubingen, and
      Freiburg between 1997 and 2010 and CB2 mRNA expression in previously published
      DNA microarray datasets. The role of CB2 in oncogenesis was studied by generating
      a mouse line that expresses the human V-Erb-B2 Avian Erythroblastic Leukemia
      Viral Oncogene Homolog 2 (HER2) rat ortholog (neu) and lacks CB2 and by a variety
      of biochemical and cell biology approaches in human breast cancer cells in
      culture and in vivo, upon modulation of CB2 expression by si/shRNAs and
      overexpression plasmids. CB2-HER2 molecular interaction was studied by
      colocalization, coimmunoprecipitation, and proximity ligation assays. Statistical
      tests were two-sided. RESULTS: We show an association between elevated CB2
      expression in HER2+ breast tumors and poor patient prognosis (decreased overall
      survival, hazard ratio [HR] = 0.29, 95% confidence interval [CI] = 0.09 to 0.71,
      P = .009) and higher probability to suffer local recurrence (HR = 0.09, 95% CI =
      0.049 to 0.54, P = .003) and to develop distant metastases (HR = 0.33, 95% CI =
      0.13 to 0.75, P = .009). We also demonstrate that genetic inactivation of CB2
      impairs tumor generation and progression in MMTV-neu mice. Moreover, we show that
      HER2 upregulates CB2 expression by activating the transcription factor ELK1 via
      the ERK cascade and that an increased CB2 expression activates the HER2 pro
      oncogenic signaling at the level of the tyrosine kinase c-SRC. Finally, we show
      HER2 and CB2 form heteromers in cancer cells. CONCLUSIONS: Our findings reveal an
      unprecedented role of CB2 as a pivotal regulator of HER2 pro-oncogenic signaling
      in breast cancer, and they suggest that CB2 may be a biomarker with prognostic
      value in these tumors.

PMID- 25855727
TI  - Temperature-Sensitive Mutants in the Influenza A Virus RNA Polymerase:
      Alterations in the PA Linker Reduce Nuclear Targeting of the PB1-PA Dimer and
      Result in Viral Attenuation.
AB  - The influenza virus RNA-dependent RNA polymerase catalyzes genome replication and
      transcription within the cell nucleus. Efficient nuclear import and assembly of
      the polymerase subunits PB1, PB2, and PA are critical steps in the virus life
      cycle. We investigated the structure and function of the PA linker (residues 197
      to 256), located between its N-terminal endonuclease domain and its C-terminal
      structured domain that binds PB1, the polymerase core. Circular dichroism
      experiments revealed that the PA linker by itself is structurally disordered. A
      large series of PA linker mutants exhibited a temperature-sensitive (ts)
      phenotype (reduced viral growth at 39.5 degrees C versus 37 degrees C/33 degrees
      C), suggesting an alteration of folding kinetic parameters. The ts phenotype was
      associated with a reduced efficiency of replication/transcription of a
      pseudoviral reporter RNA in a minireplicon assay. Using a fluorescent-tagged PB1,
      we observed that ts and lethal PA mutants did not efficiently recruit PB1 to
      reach the nucleus at 39.5 degrees C. A protein complementation assay using PA
      mutants, PB1, and beta-importin IPO5 tagged with fragments of the Gaussia
      princeps luciferase showed that increasing the temperature negatively modulated
      the PA-PB1 and the PA-PB1-IPO5 interactions or complex stability. The selection
      of revertant viruses allowed the identification of different types of
      compensatory mutations located in one or the other of the three polymerase
      subunits. Two ts mutants were shown to be attenuated and able to induce
      antibodies in mice. Taken together, our results identify a PA domain critical for
      PB1-PA nuclear import and that is a "hot spot" to engineer ts mutants that could
      be used to design novel attenuated vaccines. IMPORTANCE: By targeting a discrete
      domain of the PA polymerase subunit of influenza virus, we were able to identify
      a series of 9 amino acid positions that are appropriate to engineer temperature
      sensitive (ts) mutants. This is the first time that a large number of ts
      mutations were engineered in such a short domain, demonstrating that rational
      design of ts mutants can be achieved. We were able to associate this phenotype
      with a defect of transport of the PA-PB1 complex into the nucleus. Reversion
      substitutions restored the ability of the complex to move to the nucleus. Two of
      these ts mutants were shown to be attenuated and able to produce antibodies in
      mice. These results are of high interest for the design of novel attenuated
      vaccines and to develop new antiviral drugs.

PMID- 25855728
TI  - Zinc binding activity of human metapneumovirus M2-1 protein is indispensable for
      viral replication and pathogenesis in vivo.
AB  - Human metapneumovirus (hMPV) is a member of the Pneumovirinae subfamily in the
      Paramyxoviridae family that causes respiratory tract infections in humans. Unlike
      members of the Paramyxovirinae subfamily, the polymerase complex of pneumoviruses
      requires an additional cofactor, the M2-1 protein, which functions as a
      transcriptional antitermination factor. The M2-1 protein was found to incorporate
      zinc ions, although the specific role(s) of the zinc binding activity in viral
      replication and pathogenesis remains unknown. In this study, we found that the
      third cysteine (C21) and the last histidine (H25) in the zinc binding motif
      (CCCH) of hMPV M2-1 were essential for zinc binding activity, whereas the first
      two cysteines (C7 and C15) play only minor or redundant roles in zinc binding. In
      addition, the zinc binding motif is essential for the oligomerization of M2-1.
      Subsequently, recombinant hMPVs (rhMPVs) carrying mutations in the zinc binding
      motif were recovered. Interestingly, rhMPV-C21S and -H25L mutants, which lacked
      zinc binding activity, had delayed replication in cell culture and were highly
      attenuated in cotton rats. In contrast, rhMPV-C7S and -C15S strains, which
      retained 60% of the zinc binding activity, replicated as efficiently as rhMPV in
      cotton rats. Importantly, rhMPVs that lacked zinc binding activity triggered high
      levels of neutralizing antibody and provided complete protection against
      challenge with rhMPV. Taken together, these results demonstrate that zinc binding
      activity is indispensable for viral replication and pathogenesis in vivo. These
      results also suggest that inhibition of zinc binding activity may serve as a
      novel approach to rationally attenuate hMPV and perhaps other pneumoviruses for
      vaccine purposes. IMPORTANCE: The pneumoviruses include many important human and
      animal pathogens, such as human respiratory syncytial virus (hRSV), hMPV, bovine
      RSV, and avian metapneumovirus (aMPV). Among these viruses, hRSV and hMPV are the
      leading causes of acute respiratory tract infection in infants and children.
      Despite major efforts, there is no antiviral or vaccine to combat these diseases.
      All known pneumoviruses encode a zinc binding protein, M2-1, which is a
      transcriptional antitermination factor. In this work, we found that the zinc
      binding activity of M2-1 is essential for virus replication and pathogenesis in
      vivo. Recombinant hMPVs that lacked zinc binding activity were not only defective
      in replication in the upper and lower respiratory tract but also triggered a
      strong protective immunity in cotton rats. Thus, inhibition of M2-1 zinc binding
      activity can lead to the development of novel, live attenuated vaccines, as well
      as antiviral drugs for pneumoviruses.

PMID- 25855729
TI  - The Greater Affinity of JC Polyomavirus Capsid for alpha2,6-Linked Lactoseries
      Tetrasaccharide c than for Other Sialylated Glycans Is a Major Determinant of
      Infectivity.
AB  - The human JC polyomavirus (JCPyV) establishes an asymptomatic, persistent
      infection in the kidneys of the majority of the population and is the causative
      agent of the fatal demyelinating disease progressive multifocal
      leukoencephalopathy (PML) in immunosuppressed individuals. The Mad-1 strain of
      JCPyV, a brain isolate, was shown earlier to require alpha2,6-linked sialic acid
      on the lactoseries tetrasaccharide c (LSTc) glycan for attachment to host cells.
      In contrast, a JCPyV kidney isolate type 3 strain, WT3, has been reported to
      interact with sialic acid-containing gangliosides, but the role of these glycans
      in JCPyV infection has remained unclear. To help rationalize these findings and
      probe the effects of strain-specific differences on receptor binding, we
      performed a comprehensive analysis of the glycan receptor specificities of these
      two representative JCPyV strains using high-resolution X-ray crystallography and
      nuclear magnetic resonance (NMR) spectroscopy, and correlated these data with the
      results of infectivity assays. We show here that capsid proteins of Mad-1 and WT3
      JCPyV can both engage LSTc as well as multiple sialylated gangliosides. However,
      the binding affinities exhibit subtle differences, with the highest affinity
      observed for LSTc. Engagement of LSTc is a prerequisite for functional receptor
      engagement, while the more weakly binding gangliosides are not required for
      productive infection. Our findings highlight the complexity of virus-carbohydrate
      interactions and demonstrate that subtle differences in binding affinities,
      rather than the binding event alone, help determine tissue tropism and viral
      pathogenesis. IMPORTANCE: Viral infection is initiated by attachment to receptors
      on host cells, and this event plays an important role in viral disease. We
      investigated the receptor-binding properties of human JC polyomavirus (JCPyV), a
      virus that resides in the kidneys of the majority of the population and can cause
      the fatal demyelinating disease progressive multifocal leukoencephalopathy (PML)
      in the brains of immunosuppressed individuals. JCPyV has been reported to
      interact with multiple carbohydrate receptors, and we sought to clarify how the
      interactions between JCPyV and cellular carbohydrate receptors influenced
      infection. Here we demonstrate that JCPyV can engage numerous sialylated
      carbohydrate receptors. However, the virus displays preferential binding to LSTc,
      and only LSTc mediates a productive infection. Our findings demonstrate that
      subtle differences in binding affinity, rather than receptor engagement alone,
      are a key determinant of viral infection.

PMID- 25855730
TI  - Genetic Determinants of Japanese Encephalitis Virus Vaccine Strain SA14-14-2 That
      Govern Attenuation of Virulence in Mice.
AB  - The safety and efficacy of the live-attenuated Japanese encephalitis virus (JEV)
      SA14-14-2 vaccine are attributed to mutations that accumulated in the viral
      genome during its derivation. However, little is known about the contribution
      that is made by most of these mutations to virulence attenuation and vaccine
      immunogenicity. Here, we generated recombinant JEV (rJEV) strains containing JEV
      SA14-14-2 vaccine-specific mutations that are located in the untranslated regions
      (UTRs) and seven protein genes or are introduced from PCR-amplified regions of
      the JEV SA14-14-2 genome. The resulting mutant viruses were evaluated in tissue
      culture and in mice. The authentic JEV SA14-14-2 (E) protein, with amino acid
      substitutions L107F, E138K, I176V, T177A, E244G, Q264H, K279M, A315V, S366A, and
      K439R relative to the wild-type rJEV clone, was essential and sufficient for
      complete attenuation of neurovirulence. Individually, the nucleotide substitution
      T39A in the 5' UTR (5'-UTR-T39A), the capsid (C) protein amino acid substitution
      L66S (C-L66S), and the complete NS1/2A genome region containing 10 mutations each
      significantly reduced virus neuroinvasion but not neurovirulence. The levels of
      peripheral virulence attenuation imposed by the 5'-UTR-T39A and C-L66S mutations,
      individually, were somewhat mitigated in combination with other vaccine strain
      specific mutations, which might be compensatory, and together did not affect
      immunogenicity. However, a marked reduction in immunogenicity was observed with
      the addition of the NS1/2A and NS5 vaccine virus genome regions. These results
      suggest that a second-generation recombinant vaccine can be rationally engineered
      to maximize levels of immunogenicity without compromising safety. IMPORTANCE: The
      live-attenuated JEV SA14-14-2 vaccine has been vital for controlling the
      incidence of disease caused by JEV, particularly in rural areas of Asia where it
      is endemic. The vaccine was developed >25 years ago by passaging wild-type JEV
      strain SA14 in tissue cultures and rodents, with intermittent tissue culture
      plaque purifications, to produce a virus clone that had adequate levels of
      attenuation and immunogenicity. The vaccine and parent virus sequences were later
      compared, and mutations were identified throughout the vaccine virus genome, but
      their contributions to attenuation were never fully elucidated. Here, using
      reverse genetics, we comprehensively defined the impact of JEV SA14-14-2
      mutations on attenuation of virulence and immunogenicity in mice. These results
      are relevant for quality control of new lots of the current live-attenuated
      vaccine and provide insight for the rational design of second-generation, live
      attenuated, recombinant JEV vaccine candidates.

PMID- 25855732
TI  - Creation of matrix protein gene variants of two serotypes of vesicular stomatitis
      virus as prime-boost vaccine vectors.
AB  - To take advantage of live recombinant vesicular stomatitis viruses (rVSVs) as
      vaccine vectors for their high yield and for their induction of strong and long
      lasting immune responses, it is necessary to make live vaccine vectors safe for
      use without losing their immunogenicity. We have generated safer and highly
      efficient recombinant VSV vaccine vectors by combining the M51R mutation in the M
      gene of serotype VSV-Indiana (VSVInd) with a temperature-sensitive mutation
      (tsO23) of the VSVInd Orsay strain. In addition, we have generated two new
      serotype VSV-New Jersey (VSVNJ) vaccine vectors by combining M48R and M51R
      mutations with G22E and L110F mutations in the M gene, rVSVNJ(G22E M48R M51R)
      [rVSVNJ(GMM)] and VSVNJ(G22E M48R M51R L110F) [rVSVNJ(GMML)]. The combined
      mutations G21E, M51R, and L111F in the M protein of VSVInd significantly reduced
      the burst size of the virus by up to 10,000-fold at 37 degrees C without
      affecting the level of protein expression. BHK21 cells and SH-SY5Y human
      neuroblastoma cells infected with rVSVInd(GML), rVSVNJ(GMM), and rVSVNJ(GMML)
      showed significantly reduced cytopathic effects in vitro at 37 degrees C, and
      mice injected with 1 million infectious virus particles of these mutants into the
      brain showed no neurological dysfunctions or any other adverse effects. In order
      to increase the stability of the temperature-sensitive mutant, we have replaced
      the phenylalanine with alanine. This will change all three nucleotides from UUG
      (leucine) to GCA (alanine). The resulting L111A mutant showed the temperature
      sensitive phenotype of rVSVInd(GML) and increased stability. Twenty consecutive
      passages of rVSVInd(GML) with an L111A mutation did not convert back to leucine
      (UUG) at position 111 in the M protein gene. IMPORTANCE: Recombinant vesicular
      stomatitis viruses as live vaccine vectors are very effective in expressing
      foreign genes and inducing adaptive T cell and B cell immune responses. As with
      any other live viruses in humans or animals, the use of live rVSVs as vaccine
      vectors demands the utmost safety. Our strategy to attenuate rVSVInd by utilizing
      a temperature-sensitive assembly-defective mutation of L111A and combining it
      with an M51R mutation in the M protein of rVSVInd significantly reduced the
      pathogenicity of the virus while maintaining highly effective virus production.
      We believe our new temperature-sensitive M gene mutant of rVSVInd(GML) and M gene
      mutants of rVSVNJ(GMM) and rVSVNJ(GMML) add excellent vaccine vectors to the pool
      of live viral vectors.

PMID- 25855731
TI  - Molecular chaperone Hsp90 is a therapeutic target for noroviruses.
AB  - Human noroviruses (HuNoV) are a significant cause of acute gastroenteritis in the
      developed world, and yet our understanding of the molecular pathways involved in
      norovirus replication and pathogenesis has been limited by the inability to
      efficiently culture these viruses in the laboratory. Using the murine norovirus
      (MNV) model, we have recently identified a network of host factors that interact
      with the 5' and 3' extremities of the norovirus RNA genome. In addition to a
      number of well-known cellular RNA binding proteins, the molecular chaperone Hsp90
      was identified as a component of the ribonucleoprotein complex. Here, we show
      that the inhibition of Hsp90 activity negatively impacts norovirus replication in
      cell culture. Small-molecule-mediated inhibition of Hsp90 activity using 17-DMAG
      (17-dimethylaminoethylamino-17-demethoxygeldanamycin) revealed that Hsp90 plays a
      pleiotropic role in the norovirus life cycle but that the stability of the viral
      capsid protein is integrally linked to Hsp90 activity. Furthermore, we
      demonstrate that both the MNV-1 and the HuNoV capsid proteins require Hsp90
      activity for their stability and that targeting Hsp90 in vivo can significantly
      reduce virus replication. In summary, we demonstrate that targeting cellular
      proteostasis can inhibit norovirus replication, identifying a potential novel
      therapeutic target for the treatment of norovirus infections. IMPORTANCE: HuNoV
      are a major cause of acute gastroenteritis around the world. RNA viruses,
      including noroviruses, rely heavily on host cell proteins and pathways for all
      aspects of their life cycle. Here, we identify one such protein, the molecular
      chaperone Hsp90, as an important factor required during the norovirus life cycle.
      We demonstrate that both murine and human noroviruses require the activity of
      Hsp90 for the stability of their capsid proteins. Furthermore, we demonstrate
      that targeting Hsp90 activity in vivo using small molecule inhibitors also
      reduces infectious virus production. Given the considerable interest in the
      development of Hsp90 inhibitors for use in cancer therapeutics, we identify here
      a new target that could be explored for the development of antiviral strategies
      to control norovirus outbreaks and treat chronic norovirus infection in
      immunosuppressed patients.

PMID- 25855733
TI  - SRSF1 RNA Recognition Motifs Are Strong Inhibitors of HIV-1 Replication.
AB  - Replication of the integrated HIV-1 genome is tightly regulated by a series of
      cellular factors. In previous work we showed that transactivation of the HIV-1
      promoter is regulated by the cellular splicing factor SRSF1. Here we report that
      SRSF1 can downregulate the replication of B, C, and D subtype viruses by >200
      fold in a cell culture system. We show that viral transcription and splicing are
      inhibited by SRSF1 expression. Furthermore, SRSF1 deletion mutants containing the
      protein RNA-binding domains but not the arginine serine-rich activator domain can
      downregulate viral replication by >2,000-fold with minimal impact on cell
      viability and apoptosis. These data suggest a therapeutic potential for SRSF1 and
      its RNA-binding domains. IMPORTANCE: Most drugs utilized to treat the HIV-1
      infection are based on compounds that directly target proteins encoded by the
      virus. However, given the high viral mutation rate, the appearance of novel drug
      resistant viral strains is common. Thus, there is a need for novel therapeutics
      with diverse mechanisms of action. In this study, we show that the cellular
      protein SRSF1 is a strong inhibitor of viral replication. Furthermore, expression
      of the SRSF1 RNA-binding domains alone can inhibit viral replication by >2,000
      fold in multiple viral strains without impacting cell viability. Given the strong
      antiviral properties of this protein, the RNA-binding domains, and the minimal
      effects observed on cell metabolism, further studies are warranted to assess the
      therapeutic potential of peptides derived from these sequences.

PMID- 25855734
TI  - Genetic Confirmation that the H5 Protein Is Required for Vaccinia Virus DNA
      Replication.
AB  - The duplication of the poxvirus double-stranded DNA genome occurs in cytoplasmic
      membrane-delimited factories. This physical autonomy from the host nucleus
      suggests that poxvirus genomes encode the full repertoire of proteins committed
      for genome replication. Biochemical and genetic analyses have confirmed that six
      viral proteins are required for efficient DNA synthesis; indirect evidence has
      suggested that the multifunctional H5 protein may also have a role. Here we show
      that H5 localizes to replication factories, as visualized by immunofluorescence
      and immunoelectron microscopy, and can be retrieved upon purification of the
      viral polymerase holoenzyme complex. The temperature-sensitive (ts) mutant Dts57,
      which was generated by chemical mutagenesis and has a lesion in H5, exhibits
      defects in DNA replication and morphogenesis under nonpermissive conditions,
      depending upon the experimental protocol. The H5 variant encoded by the genome of
      this mutant is ts for function but not stability. For a more precise
      investigation of how H5 contributes to DNA synthesis, we placed the ts57 H5
      allele in an otherwise wild-type viral background and also performed small
      interfering RNA-mediated depletion of H5. Finally, we generated a complementing
      cell line, CV-1-H5, which allowed us to generate a viral recombinant in which the
      H5 open reading frame was deleted and replaced with mCherry (vDeltaH5). Analysis
      of vDeltaH5 allowed us to demonstrate conclusively that viral DNA replication is
      abrogated in the absence of H5. The loss of H5 does not compromise the
      accumulation of other early viral replication proteins or the uncoating of the
      virion core, suggesting that H5 plays a direct and essential role in facilitating
      DNA synthesis. IMPORTANCE: Variola virus, the causative agent of smallpox, is the
      most notorious member of the Poxviridae family. Poxviruses are unique among DNA
      viruses that infect mammalian cells, in that their replication is restricted to
      the cytoplasm of the cell. This physical autonomy from the nucleus has both cell
      biological and genetic ramifications. Poxviruses must establish cytoplasmic
      niches that support replication, and the genomes must encode the repertoire of
      proteins necessary for genome synthesis. Here we focus on H5, a multifunctional
      and abundant viral protein. We confirm that H5 associates with the DNA polymerase
      holoenzyme and localizes to the sites of DNA synthesis. By generating an H5
      expressing cell line, we were able to isolate a deletion virus that lacks the H5
      gene and show definitively that genome synthesis does not occur in the absence of
      H5. These data support the hypothesis that H5 is a crucial participant in
      cytoplasmic poxvirus genome replication.

PMID- 25855735
TI  - Interaction between Shadoo and PrP Affects the PrP-Folding Pathway.
AB  - Prion diseases are characterized by conformational changes of a cellular prion
      protein (PrP(C)) into a beta-sheet-enriched and aggregated conformer (PrP(Sc)).
      Shadoo (Sho), a member of the prion protein family, is expressed in the central
      nervous system (CNS) and is highly conserved among vertebrates. On the basis of
      histoanatomical colocalization and sequence similarities, it is suspected that
      Sho and PrP may be functionally related. The downregulation of Sho expression
      during prion pathology and the direct interaction between Sho and PrP, as
      revealed by two-hybrid analysis, suggest a relationship between Sho and prion
      replication. Using biochemical and biophysical approaches, we demonstrate that
      Sho forms a 1:1 complex with full-length PrP with a dissociation constant in the
      micromolar range, and this interaction consequently modifies the PrP-folding
      pathway. Using a truncated PrP that mimics the C-terminal C1 fragment, an
      allosteric binding behavior with a Hill number of 4 was observed, suggesting that
      at least a tetramerization state occurs. A cell-based prion titration assay
      performed with different concentrations of Sho revealed an increase in the
      PrP(Sc) conversion rate in the presence of Sho. Collectively, our observations
      suggest that Sho can affect the prion replication process by (i) acting as a
      holdase and (ii) interfering with the dominant-negative inhibitor effect of the
      C1 fragment. IMPORTANCE: Since the inception of the prion theory, the search for
      a cofactor involved in the conversion process has been an active field of
      research. Although the PrP interactome presents a broad landscape, candidates
      corresponding to specific criteria for cofactors are currently missing. Here, we
      describe for the first time that Sho can affect PrP structural dynamics and
      therefore increase the prion conversion rate. A biochemical characterization of
      Sho-PrP indicates that Sho acts as an ATP-independent holdase.

PMID- 25855736
TI  - Regulation of Hepatitis C Virus Genome Replication by Xrn1 and MicroRNA-122
      Binding to Individual Sites in the 5' Untranslated Region.
AB  - miR-122 is a liver-specific microRNA (miRNA) that binds to two sites (S1 and S2)
      on the 5' untranslated region (UTR) of the hepatitis C virus (HCV) genome and
      promotes the viral life cycle. It positively affects viral RNA stability,
      translation, and replication, but the mechanism is not well understood. To
      unravel the roles of miR-122 binding at each site alone or in combination, we
      employed miR-122 binding site mutant viral RNAs, Hep3B cells (which lack
      detectable miR-122), and complementation with wild-type miR-122, an miR-122 with
      the matching mutation, or both. We found that miR-122 binding at either site
      alone increased replication equally, while binding at both sites had a
      cooperative effect. Xrn1 depletion rescued miR-122-unbound full-length RNA
      replication to detectable levels but not to miR-122-bound levels, confirming that
      miR-122 protects HCV RNA from Xrn1, a cytoplasmic 5'-to-3' exoribonuclease, but
      also has additional functions. In cells depleted of Xrn1, replication levels of
      S1-bound HCV RNA were slightly higher than S2-bound RNA levels, suggesting that
      both sites contribute, but their contributions may be unequal when the need for
      protection from Xrn1 is reduced. miR-122 binding at S1 or S2 also increased
      translation equally, but the effect was abolished by Xrn1 knockdown, suggesting
      that the influence of miR-122 on HCV translation reflects protection from Xrn1
      degradation. Our results show that occupation of each miR-122 binding site
      contributes equally and cooperatively to HCV replication but suggest somewhat
      unequal contributions of each site to Xrn1 protection and additional functions of
      miR-122. IMPORTANCE: The functions of miR-122 in the promotion of the HCV life
      cycle are not fully understood. Here, we show that binding of miR-122 to each of
      the two binding sites in the HCV 5' UTR contributes equally to HCV replication
      and that binding to both sites can function cooperatively. This suggests that
      active Ago2-miR-122 complexes assemble at each site and can cooperatively promote
      the association and/or function of adjacent complexes, similar to what has been
      proposed for translation suppression by adjacent miRNA binding sites. We also
      confirm a role for miR-122 in protection from Xrn1 and provide evidence that miR
      122 has additional functions in the HCV life cycle unrelated to Xrn1. Finally, we
      show that each binding site may contribute unequally to Xrn1 protection and other
      miR-122 functions.

PMID- 25855737
TI  - Investigating influenza A virus infection: tools to track infection and limit
      tropism.
AB  - Influenza A viruses display a broad cellular tropism within the respiratory
      tracts of mammalian hosts. Uncovering the relationship between tropism and virus
      immunity, pathogenesis, and transmission will be critical for the development of
      therapeutic interventions. Here we discuss recent developments of several
      recombinant strains of influenza A virus. These viruses have inserted reporters
      to track tropism, microRNA target sites to restrict tropism, or barcodes to
      assess transmission dynamics, expanding our understanding of pathogen-host
      interactions. 

PMID- 25855738
TI  - Genetics, Receptor Binding, and Virulence in Mice of H10N8 Influenza Viruses
      Isolated from Ducks and Chickens in Live Poultry Markets in China.
AB  - We analyzed eight H10N8 viruses isolated from ducks and chickens in live poultry
      markets from 2009 to 2013 in China. These viruses showed distinct genetic
      diversity and formed five genotypes: the four duck isolates formed four different
      genotypes, whereas the four chicken viruses belong to a single genotype. The
      viruses bound to both human- and avian-type receptors, and four of the viruses
      caused 12.7% to 22.5% body weight loss in mice. 

PMID- 25855739
TI  - A single amino acid deletion in the matrix protein of porcine reproductive and
      respiratory syndrome virus confers resistance to a polyclonal swine antibody with
      broadly neutralizing activity.
AB  - Assessment of virus neutralization (VN) activity in 176 pigs infected with
      porcine reproductive and respiratory syndrome virus (PRRSV) identified one pig
      with broadly neutralizing activity. A Tyr-10 deletion in the matrix protein
      provided escape from broad neutralization without affecting homologous
      neutralizing activity. The role of the Tyr-10 deletion was confirmed through an
      infectious clone with a Tyr-10 deletion. The results demonstrate differences in
      the properties and specificities of VN responses elicited during PRRSV infection.

PMID- 25855740
TI  - Transformation with oncogenic Ras and the simian virus 40 T antigens induces
      caspase-dependent sensitivity to fatty acid biosynthetic inhibition.
AB  - Oncogenesis is frequently accompanied by the activation of specific metabolic
      pathways. One such pathway is fatty acid biosynthesis, whose induction is
      observed upon transformation of a wide variety of cell types. Here, we explored
      how defined oncogenic alleles, specifically the simian virus 40 (SV40) T antigens
      and oncogenic Ras(12V), affect fatty acid metabolism. Our results indicate that
      SV40/Ras(12V)-mediated transformation of fibroblasts induces fatty acid
      biosynthesis in the absence of significant changes in the concentration of fatty
      acid biosynthetic enzymes. This oncogene-induced activation of fatty acid
      biosynthesis was found to be mammalian target of rapamycin (mTOR) dependent, as
      it was attenuated by rapamycin treatment. Furthermore, SV40/Ras(12V)-mediated
      transformation induced sensitivity to treatment with fatty acid biosynthetic
      inhibitors. Pharmaceutical inhibition of acetyl-coenzyme A (CoA) carboxylase
      (ACC), a key fatty acid biosynthetic enzyme, induced caspase-dependent cell death
      in oncogene-transduced cells. In contrast, isogenic nontransformed cells were
      resistant to fatty acid biosynthetic inhibition. This oncogene-induced
      sensitivity to fatty acid biosynthetic inhibition was independent of the cells'
      growth rates and could be attenuated by supplementing the medium with unsaturated
      fatty acids. Both the activation of fatty acid biosynthesis and the sensitivity
      to fatty acid biosynthetic inhibition could be conveyed to nontransformed breast
      epithelial cells through transduction with oncogenic Ras(12V). Similar to what
      was observed in the transformed fibroblasts, the Ras(12V)-induced sensitivity to
      fatty acid biosynthetic inhibition was independent of the proliferative status
      and could be attenuated by supplementing the medium with unsaturated fatty acids.
      Combined, our results indicate that specific oncogenic alleles can directly
      confer sensitivity to inhibitors of fatty acid biosynthesis. IMPORTANCE: Viral
      oncoproteins and cellular mutations drive the transformation of normal cells to
      the cancerous state. These oncogenic alterations induce metabolic changes and
      dependencies that can be targeted to kill cancerous cells. Here, we find that the
      cellular transformation resulting from combined expression of the SV40 early
      region with an oncogenic Ras allele is sufficient to induce cellular
      susceptibility to fatty acid biosynthetic inhibition. Inhibition of fatty acid
      biosynthesis in these cells resulted in programmed cell death, which could be
      rescued by supplementing the medium with nonsaturated fatty acids. Similar
      results were observed with the expression of oncogenic Ras in nontransformed
      breast epithelial cells. Combined, our results suggest that specific oncogenic
      alleles induce metabolic dependencies that can be exploited to selectively kill
      cancerous cells.

PMID- 25855741
TI  - Comparison of Immunogenicity in Rhesus Macaques of Transmitted-Founder, HIV-1
      Group M Consensus, and Trivalent Mosaic Envelope Vaccines Formulated as a DNA
      Prime, NYVAC, and Envelope Protein Boost.
AB  - An effective human immunodeficiency virus type 1 (HIV-1) vaccine must induce
      protective antibody responses, as well as CD4(+) and CD8(+) T cell responses,
      that can be effective despite extraordinary diversity of HIV-1. The consensus and
      mosaic immunogens are complete but artificial proteins, computationally designed
      to elicit immune responses with improved cross-reactive breadth, to attempt to
      overcome the challenge of global HIV diversity. In this study, we have compared
      the immunogenicity of a transmitted-founder (T/F) B clade Env (B.1059), a global
      group M consensus Env (Con-S), and a global trivalent mosaic Env protein in
      rhesus macaques. These antigens were delivered using a DNA prime-recombinant
      NYVAC (rNYVAC) vector and Env protein boost vaccination strategy. While Con-S Env
      was a single sequence, mosaic immunogens were a set of three Envs optimized to
      include the most common forms of potential T cell epitopes. Both Con-S and mosaic
      sequences retained common amino acids encompassed by both antibody and T cell
      epitopes and were central to globally circulating strains. Mosaics and Con-S Envs
      expressed as full-length proteins bound well to a number of neutralizing
      antibodies with discontinuous epitopes. Also, both consensus and mosaic
      immunogens induced significantly higher gamma interferon (IFN-gamma) enzyme
      linked immunosorbent spot assay (ELISpot) responses than B.1059 immunogen.
      Immunization with these proteins, particularly Con-S, also induced significantly
      higher neutralizing antibodies to viruses than B.1059 Env, primarily to tier 1
      viruses. Both Con-S and mosaics stimulated more potent CD8-T cell responses
      against heterologous Envs than did B.1059. Both antibody and cellular data from
      this study strengthen the concept of using in silico-designed centralized
      immunogens for global HIV-1 vaccine development strategies. IMPORTANCE: There is
      an increasing appreciation for the importance of vaccine-induced anti-Env
      antibody responses for preventing HIV-1 acquisition. This nonhuman primate study
      demonstrates that in silico-designed global HIV-1 immunogens, designed for a
      human clinical trial, are capable of eliciting not only T lymphocyte responses
      but also potent anti-Env antibody responses.

PMID- 25855742
TI  - Interaction between TIM-1 and NPC1 Is Important for Cellular Entry of Ebola
      Virus.
AB  - Multiple host molecules are known to be involved in the cellular entry of
      filoviruses, including Ebola virus (EBOV); T-cell immunoglobulin and mucin domain
      1 (TIM-1) and Niemann-Pick C1 (NPC1) have been identified as attachment and
      fusion receptors, respectively. However, the molecular mechanisms underlying the
      entry process have not been fully understood. We found that TIM-1 and NPC1
      colocalized and interacted in the intracellular vesicles where EBOV glycoprotein
      (GP)-mediated membrane fusion occurred. Interestingly, a TIM-1-specific
      monoclonal antibody (MAb), M224/1, prevented GP-mediated membrane fusion and also
      interfered with the binding of TIM-1 to NPC1, suggesting that the interaction
      between TIM-1 and NPC1 is important for filovirus membrane fusion. Moreover, MAb
      M224/1 efficiently inhibited the cellular entry of viruses from all known
      filovirus species. These data suggest a novel mechanism underlying filovirus
      membrane fusion and provide a potential cellular target for antiviral compounds
      that can be universally used against filovirus infections. IMPORTANCE:
      Filoviruses, including Ebola and Marburg viruses, cause rapidly fatal diseases in
      humans and nonhuman primates. There are currently no approved vaccines or
      therapeutics for filovirus diseases. In general, the cellular entry step of
      viruses is one of the key mechanisms to develop antiviral strategies. However,
      the molecular mechanisms underlying the entry process of filoviruses have not
      been fully understood. In this study, we demonstrate that TIM-1 and NPC1, which
      serve as attachment and fusion receptors for filovirus entry, interact in the
      intracellular vesicles where Ebola virus GP-mediated membrane fusion occurs and
      that this interaction is important for filovirus infection. We found that
      filovirus infection and GP-mediated membrane fusion in cultured cells were
      remarkably suppressed by treatment with a TIM-1-specific monoclonal antibody that
      interfered with the interaction between TIM-1 and NPC1. Our data provide new
      insights for the development of antiviral compounds that can be universally used
      against filovirus infections.

PMID- 25855743
TI  - HIV Blocks Interferon Induction in Human Dendritic Cells and Macrophages by
      Dysregulation of TBK1.
AB  - Dendritic cells (DCs) and macrophages are present in the tissues of the
      anogenital tract, where HIV-1 transmission occurs in almost all cases. These
      cells are both target cells for HIV-1 and represent the first opportunity for the
      virus to interfere with innate recognition. Previously we have shown that both
      cell types fail to produce type I interferons (IFNs) in response to HIV-1 but
      that, unlike T cells, the virus does not block IFN induction by targeting IFN
      regulatory factor 3 (IRF3) for cellular degradation. Thus, either HIV-1 inhibits
      IFN induction by an alternate mechanism or, less likely, these cells fail to
      sense HIV-1. Here we show that HIV-1 (but not herpes simplex virus 2 [HSV-2] or
      Sendai virus)-exposed DCs and macrophages fail to induce the expression of all
      known type I and III IFN genes. These cells do sense the virus, and pattern
      recognition receptor (PRR)-induced signaling pathways are triggered. The precise
      stage in the IFN-inducing signaling pathway that HIV-1 targets to block IFN
      induction was identified; phosphorylation but not K63 polyubiquitination of TANK
      binding kinase 1 (TBK1) was completely inhibited. Two HIV-1 accessory proteins,
      Vpr and Vif, were shown to bind to TBK1, and their individual deletion partly
      restored IFN-beta expression. Thus, the inhibition of TBK1 autophosphorylation by
      binding of these proteins appears to be the principal mechanism by which HIV-1
      blocks type I and III IFN induction in myeloid cells. IMPORTANCE: Dendritic cells
      (DCs) and macrophages are key HIV target cells. Therefore, definition of how HIV
      impairs innate immune responses to initially establish infection is essential to
      design preventative interventions, especially by restoring initial interferon
      production. Here we demonstrate how HIV-1 blocks interferon induction by
      inhibiting the function of a key kinase in the interferon signaling pathway,
      TBK1, via two different viral accessory proteins. Other viral proteins have been
      shown to target the general effects of TBK1, but this precise targeting between
      ubiquitination and phosphorylation of TBK1 is novel.

PMID- 25855744
TI  - Genomic, phylogenetic, and recombinational characterization of herpes simplex
      virus 2 strains.
AB  - Herpes simplex virus 2 (HSV-2) is a major global pathogen, infecting 16% of
      people 15 to 49 years old worldwide and causing recurrent genital ulcers. Little
      is known about viral factors contributing to virulence, and there are currently
      only two genomic sequences available. In this study, we determined nearly
      complete genomic sequences of six additional HSV-2 isolates, using Illumina
      MiSeq. We report that HSV-2 has a genomic overall mean distance of 0.2355%, which
      is less than that of HSV-1. There were approximately 100 amino-acid-encoding and
      indels per genome. Microsatellite mapping found a bias toward intergenic regions
      in the nonconserved microsatellites and a genic bias in all detected tandem
      repeats. Extensive recombination between the HSV-2 strains was also strongly
      implied. This was the first study to analyze multiple HSV-2 sequences, and the
      data will be valuable in future evolutionary, virulence, and structure-function
      studies. IMPORTANCE: HSV-2 is a significant worldwide pathogen, causing recurrent
      genital ulcers. Here we present six nearly complete HSV-2 genomic sequences, and,
      with the addition of two previously sequenced strains, for the first time
      genomic, phylogenetic, and recombination analysis was performed on multiple HSV-2
      genomes. Our results show that microsatellite mapping found a bias toward
      intergenic regions in the nonconserved microsatellites and a genic bias in all
      detected tandem repeats and confirm that chimpanzee herpesvirus 1 (ChHV-1) is a
      separate species and that each of the HSV-2 strains is a genomic mosaic.

PMID- 25855745
TI  - Influenza A Virus Protein PA-X Contributes to Viral Growth and Suppression of the
      Host Antiviral and Immune Responses.
AB  - Influenza virus infection causes global inhibition of host protein synthesis in
      infected cells. This host shutoff is thought to allow viruses to escape from the
      host antiviral response, which restricts virus replication and spread. Although
      the mechanism of host shutoff is unclear, a novel viral protein expressed by
      ribosomal frameshifting, PA-X, was found to play a major role in influenza virus
      induced host shutoff. However, little is known about the impact of PA-X
      expression on currently circulating influenza A virus pathogenicity and the host
      antiviral response. In this study, we rescued a recombinant influenza A virus,
      A/California/04/09 (H1N1, Cal), containing mutations at the frameshift motif in
      the polymerase PA gene (Cal PA-XFS). Cal PA-XFS expressed significantly less PA-X
      than Cal wild type (WT). Cal WT, but not Cal PA-XFS, induced degradation of host
      beta-actin mRNA and suppressed host protein synthesis, supporting the idea that
      PA-X induces host shutoff via mRNA decay. Moreover, Cal WT inhibited beta
      interferon (IFN-beta) expression and replicated more rapidly than Cal PA-XFS in
      human respiratory cells. Mice infected with Cal PA-XFS had significantly lower
      levels of viral growth and greater expression of IFN-beta mRNA in their lungs
      than mice infected with Cal WT. Importantly, more antihemagglutinin and
      neutralizing antibodies were produced in Cal PA-XFS-infected mice than in Cal WT
      infected mice, despite the lower level of virus replication in the lungs. Our
      data indicate that PA-X of the pandemic H1N1 virus has a strong impact on viral
      growth and the host innate and acquired immune responses to influenza virus.
      IMPORTANCE: Virus-induced host protein shutoff is considered to be a major factor
      allowing viruses to evade innate and acquired immune recognition. We provide
      evidence that the 2009 H1N1 influenza A virus protein PA-X plays a role in virus
      replication and inhibition of host antiviral response by means of its host
      protein synthesis shutoff activity both in vitro and in vivo. We also
      demonstrated that, while the growth of Cal PA-XFS was attenuated in the lungs of
      infected animals, this mutant induced a stronger humoral response than Cal WT.
      Our findings clearly highlight the importance of PA-X in counteracting the host
      innate and acquired immune responses to influenza virus, an important global
      pathogen. This work demonstrates that inhibition of PA-X expression in influenza
      virus vaccine strains may provide a novel way of safely attenuating viral growth
      while inducing a more robust immune response.

PMID- 25855747
TI  - Interleukin-2 from Adaptive T Cells Enhances Natural Killer Cell Activity against
      Human Cytomegalovirus-Infected Macrophages.
AB  - Control of human cytomegalovirus (HCMV) requires a continuous immune
      surveillance, thus HCMV is the most important viral pathogen in severely
      immunocompromised individuals. Both innate and adaptive immunity contribute to
      the control of HCMV. Here, we report that peripheral blood natural killer cells
      (PBNKs) from HCMV-seropositive donors showed an enhanced activity toward HCMV
      infected autologous macrophages. However, this enhanced response was abolished
      when purified NK cells were applied as effectors. We demonstrate that this
      enhanced PBNK activity was dependent on the interleukin-2 (IL-2) secretion of
      CD4(+) T cells when reexposed to the virus. Purified T cells enhanced the
      activity of purified NK cells in response to HCMV-infected macrophages. This
      effect could be suppressed by IL-2 blocking. Our findings not only extend the
      knowledge on the immune surveillance in HCMV-namely, that NK cell-mediated innate
      immunity can be enhanced by a preexisting T cell antiviral immunity-but also
      indicate a potential clinical implication for patients at risk for severe HCMV
      manifestations due to immunosuppressive drugs, which mainly suppress IL-2
      production and T cell responsiveness. IMPORTANCE: Human cytomegalovirus (HCMV) is
      never cleared by the host after primary infection but instead establishes a
      lifelong latent infection with possible reactivations when the host's immunity
      becomes suppressed. Both innate immunity and adaptive immunity are important for
      the control of viral infections. Natural killer (NK) cells are main innate
      effectors providing a rapid response to virus-infected cells. Virus-specific T
      cells are the main adaptive effectors that are critical for the control of the
      latent infection and limitation of reinfection. In this study, we found that IL-2
      secreted by adaptive CD4(+) T cells after reexposure to HCMV enhances the
      activity of NK cells in response to HCMV-infected target cells. This is the first
      direct evidence that the adaptive T cells can help NK cells to act against HCMV
      infection.

PMID- 25855746
TI  - Murine Gammaherpesvirus 68 Pathogenesis Is Independent of Caspase-1 and Caspase
      11 in Mice and Impairs Interleukin-1beta Production upon Extrinsic Stimulation in
      Culture.
AB  - Gammaherpesviruses establish lifelong infections that are associated with the
      development of cancer. These viruses subvert many aspects of the innate and
      adaptive immune response of the host. The inflammasome, a macromolecular protein
      complex that controls inflammatory responses to intracellular danger signals
      generated by pathogens, is both activated and subverted during human
      gammaherpesvirus infection in culture. The impact of the inflammasome response on
      gammaherpesvirus replication and latency in vivo is not known. Caspase-1 is the
      inflammasome effector protease that cleaves the proinflammatory cytokines
      interleukin-1beta (IL-1beta) and IL-18. We infected caspase-1-deficient mice with
      murine gammaherpesvirus 68 (MHV68) and observed no impact on acute replication in
      the lung or latency and reactivation from latency in the spleen. This led us to
      examine the effect of viral infection on inflammasome responses in bone marrow
      derived macrophages. We determined that infection of macrophages with MHV68 led
      to a robust interferon response but failed to activate caspase-1 or induce the
      secretion of IL-1beta. In addition, MHV68 infection led to a reduction in IL
      1beta production after extrinsic lipopolysaccharide stimulation or upon
      coinfection with Salmonella enterica serovar Typhimurium. Interestingly, this
      impairment occurred at the proIL-1beta transcript level and was independent of
      the RTA, the viral lytic replication and transcription activator. Taken together,
      MHV68 impairs the inflammasome response by inhibiting IL-1beta production during
      the initial stages of infection. IMPORTANCE: Gammaherpesviruses persist for the
      lifetime of the host. To accomplish this, they must evade recognition and
      clearance by the immune system. The inflammasome consists of proteins that detect
      foreign molecules in the cell and respond by secreting proinflammatory signaling
      proteins that recruit immune cells to clear the infection. Unexpectedly, we found
      that murine gammaherpesvirus pathogenesis was not enhanced in mice lacking
      caspase-1, a critical inflammasome component. This led us to investigate whether
      the virus actively impairs the inflammasome response. We found that the
      inflammasome was not activated upon macrophage cell infection with murine
      gammaherpesvirus 68. Infection also prevented the host cell inflammasome response
      to other pathogen-associated molecular patterns, indicated by reduced production
      of the proinflammatory cytokine IL-1beta upon bacterial coinfection. Taken
      together, murine gammaherpesvirus impairment of the inflammatory cytokine IL
      1beta in macrophages identifies one mechanism by which the virus may inhibit
      caspase-1-dependent immune responses in the infected animal.

PMID- 25855748
TI  - Intercontinental Spread of Asian-Origin H5N8 to North America through Beringia by
      Migratory Birds.
AB  - Phylogenetic network analysis and understanding of waterfowl migration patterns
      suggest that the Eurasian H5N8 clade 2.3.4.4 avian influenza virus emerged in
      late 2013 in China, spread in early 2014 to South Korea and Japan, and reached
      Siberia and Beringia by summer 2014 via migratory birds. Three genetically
      distinct subgroups emerged and subsequently spread along different flyways during
      fall 2014 into Europe, North America, and East Asia, respectively. All three
      subgroups reappeared in Japan, a wintering site for waterfowl from Eurasia and
      parts of North America. 

PMID- 25855749
TI  - CD8+ T Cells Can Mediate Short-Term Protection against Heterotypic Dengue Virus
      Reinfection in Mice.
AB  - Dengue virus (DENV) is a major public health threat worldwide. Infection with one
      of the four serotypes of DENV results in a transient period of protection against
      reinfection with all serotypes (cross-protection), followed by lifelong immunity
      to the infecting serotype. While a protective role for neutralizing antibody
      responses is well established, the contribution of T cells to reinfection is less
      clear, especially during heterotypic reinfection. This study investigates the
      role of T cells during homotypic and heterotypic DENV reinfection. Mice were
      sequentially infected with homotypic or heterotypic DENV serotypes, and T cell
      subsets were depleted before the second infection to assess the role of DENV
      primed T cells during reinfection. Mice primed nonlethally with DENV were
      protected against reinfection with either a homotypic or heterotypic serotype 2
      weeks later. Homotypic priming induced a robust neutralizing antibody response,
      whereas heterotypic priming elicited binding, but nonneutralizing antibodies.
      CD8(+) T cells were required for protection against heterotypic, but not
      homotypic, reinfection. These results suggest that T cells can contribute
      crucially to protection against heterotypic reinfection in situations where
      humoral responses alone may not be protective. Our findings have important
      implications for vaccine design, as they suggest that inducing both humoral and
      cellular responses during vaccination may maximize protective efficacy across all
      DENV serotypes. IMPORTANCE: Dengue virus is present in more than 120 countries in
      tropical and subtropical regions. Infection with dengue virus can be
      asymptomatic, but it can also progress into the potentially lethal severe dengue
      disease. There are four closely related dengue virus serotypes. Infection with
      one serotype results in a transient period of resistance against all serotypes
      (cross-protection), followed by lifelong resistance to the infecting serotype,
      but not the other ones. The duration and mechanisms of the transient cross
      protection period remain elusive. This study investigates the contribution of
      cellular immunity to cross-protection using mouse models of DENV infection. Our
      results demonstrate that cellular immunity is crucial to mediate cross-protection
      against reinfection with a different serotype, but not for protection against
      reinfection with the same serotype. A better understanding of the mediators
      responsible for the cross-protection period is important for vaccine design, as
      an ideal vaccine against dengue virus should efficiently protect against all
      serotypes.

PMID- 25855751
TI  - The business case for pediatric asthma quality improvement in low-income
      populations: examining a provider-based pay-for-reporting intervention.
AB  - OBJECTIVE: To measure the return on investment (ROI) for a pediatric asthma pay
      for-reporting intervention initiated by a Medicaid managed care plan in New York
      State. DESIGN: Practice-level, randomized prospective evaluation. SETTING: Twenty
      five primary care practices providing care to children enrolled in the Monroe
      Plan for Medical Care (the Monroe Plan). PARTICIPANTS: Practices were randomized
      to either treatment (13 practices, 11 participated) or control (12 practices).
      INTERVENTION: For each of its eligible members assigned to a treatment group
      practice, the Monroe plan paid a low monthly incentive fee to the practice. To
      receive the incentive, treatment group practices were required to conduct, and
      report to the Monroe Plan, the results of chart audits on eligible members. Chart
      audits were conducted by practices every 6 months. After each chart audit, the
      Monroe Plan provided performance feedback to each practice comparing its
      adherence to asthma care guidelines with averages from all other treatment group
      practices. Control practices continued with usual care. MAIN OUTCOME MEASURES:
      Intervention implementation and operating costs and per member, per month claims
      costs. ROI was measured by net present value (discounted cash flow analysis).
      RESULTS: The ROI to the Monroe Plan was negative, primarily due to high
      intervention costs and lack of reductions in spending on emergency department and
      hospital utilization for children in treatment relative to control practices.
      CONCLUSIONS: A pay-for-reporting, chart audit intervention is unlikely to achieve
      the meaningful reductions in utilization of high-cost services that would be
      necessary to produce a financial ROI in 2.5 years.

PMID- 25855750
TI  - Mutations in coronavirus nonstructural protein 10 decrease virus replication
      fidelity.
AB  - Coronaviruses (CoVs) are unique in encoding a 3'->5' exoribonuclease within
      nonstructural protein 14 (nsp14-ExoN) that is required for high-fidelity
      replication, likely via proofreading. nsp14 associates with the CoV RNA-dependent
      RNA polymerase (nsp12-RdRp), and nsp14-ExoN activity is enhanced by binding
      nsp10, a small nonenzymatic protein. However, it is not known whether nsp10
      functions in the regulation of CoV replication fidelity. To test this, we
      engineered single and double alanine substitution mutations into the genome of
      murine hepatitis virus (MHV-A59) containing ExoN activity [ExoN(+)] at positions
      within nsp10 known to disrupt the nsp10-nsp14 interaction in vitro. We show that
      an nsp10 mutant, R80A/E82A-ExoN(+), was five to ten times more sensitive to
      treatment with the RNA mutagen 5-fluorouracil (5-FU) than wild-type (WT)-ExoN(+),
      suggestive of decreased replication fidelity. This decreased-fidelity phenotype
      was confirmed using two additional nucleoside analogs, 5-azacytidine and
      ribavirin. R80A/E82A-ExoN(+) reached a peak titer similar to and demonstrated RNA
      synthesis kinetics comparable to those seen with WT-ExoN(+). No change in 5-FU
      sensitivity was observed for R80A/E82A-ExoN(-) relative to MHV-ExoN(-),
      indicating that the decreased-fidelity phenotype of R80A/E82A-ExoN(-) is linked
      to the presence of ExoN activity. Our results demonstrate that nsp10 is important
      for CoV replication fidelity and support the hypothesis that nsp10 functions to
      regulate nsp14-ExoN activity during virus replication. IMPORTANCE: The adaptive
      capacity of CoVs, as well as all other RNA viruses, is partially attributed to
      the presence of extensive population genetic diversity. However, decreased
      fidelity is detrimental to CoV replication and virulence; mutant CoVs with
      decreased replication fidelity are attenuated and more sensitive to inhibition by
      RNA mutagens. Thus, identifying the viral protein determinants of CoV fidelity is
      important for understanding CoV replication, pathogenesis, and virulence. In this
      report, we show that nsp10, a small, nonenzymatic viral protein, contributes to
      CoV replication fidelity. Our data support the hypothesis that CoVs have evolved
      multiple proteins, in addition to nsp14-ExoN, that are responsible for
      maintaining the integrity of the largest known RNA genomes.

PMID- 25855752
TI  - To recommend the local primary health-care centre or not: what importance do
      patients attach to initial contact quality, staff continuity and responsive staff
      encounters?
AB  - OBJECTIVE: This study aims to examine the circumstances associated with patients'
      tendencies to recommend a primary care centre, based on four hypotheses, the
      initial contact's quality, care relationship continuity, treatment encounter
      responsiveness and whether the significance of encounter responsiveness differs
      depending on whether the patient has been seeing a nurse or physician. DESIGN:
      The study is based on the patient' self-reported responses, retrieved from the
      Swedish National Patient Survey. The design is cross-sectional, and data were
      analysed using a binary logistic regression. SETTING: Data were collected from
      three primary healthcare centres in the region of Vastra Gotaland, Sweden.
      PARTICIPANTS: A total of 362 patients (62% females) having visited any of three
      publicly run healthcare centres in September 2010 constitute the analytical
      sample. Participants were fairly evenly distributed across all age groups. MAIN
      OUTCOME MEASURES: Recommendation was captured by patients' binary responses to
      the question: Would you recommend the visited primary healthcare centre? RESULTS:
      The hypotheses involving initial contact quality, care relationship continuity
      and treatment encounter responsiveness were supported by the analyses. The latter
      was strongly associated with patient tendency to recommend the primary healthcare
      centre. However, the profession (nurse or physician) involved in the treatment
      encounter made no difference for the predictive significance of encounter
      responsiveness for a patient's tendency to recommend the healthcare centre.
      CONCLUSIONS: Striving for stable and responsive patient/staff relationships and
      an open approach towards patients are potentially successful strategies for
      primary healthcare centres seeking to attract new patients and maintain current
      ones.

PMID- 25855753
TI  - Technological aspects of hospital communication challenges: an observational
      study.
AB  - OBJECTIVE: To gain insights into how technological communication tools impact
      effective communication among clinicians, which is critical for patient safety.
      DESIGN: This multi-site observational study analyzes inter-clinician
      communication and interaction with information technology, with a focus on the
      critical process of patient transfer from the Emergency Department to General
      Internal Medicine. SETTING: Mount Sinai Hospital, Sunnybrook Health Sciences
      Centre and Toronto General Hospital. PARTICIPANTS: At least five ED and general
      internal medicine nurses and physicians directly involved in patient transfers
      were observed on separate occasions at each institution. INTERVENTIONS: N/A. MAIN
      OUTCOME MEASURES: N/A. RESULTS: The study provides insight into clinician
      workflow, evaluates current hospital communication systems and identifies key
      issues affecting communication: interruptions, issues with numeric pagers, lack
      of integrated communication tools, lack of awareness of consultation status,
      inefficiencies related to the paper chart, unintuitive user interfaces, mixed use
      of electronic and paper systems and lack of up-to-date contact information. It
      also identifies design trade-offs to be negotiated: synchronous communication vs.
      reducing interruptions, notification of patient status vs. reducing interruptions
      and speed vs. quality of handovers. CONCLUSIONS: The issues listed should be
      considered in the design of new technology for hospital communications.

PMID- 25855755
TI  - Gamma-carboxylation and fragmentation of osteocalcin in human serum defined by
      mass spectrometry.
AB  - Serum osteocalcin (Oc) concentration is a highly specific measure of bone
      turnover, but its circulating proteoform(s) have not been well defined. Based on
      immunological methods, the major forms are thought to be the intact polypeptide
      and a large N-terminal-mid molecule fragment for which there is no consensus on
      the precise sequence. Vitamin K-dependent gamma (gamma)-carboxylated variants of
      Oc are also found in circulation but there have been no methods that can define
      how many of the three potential gamma-carboxyglutamic acid (Gla) residues are
      gamma-carboxylated or provide their relative abundances. Recent reports that
      uncarboxylated and partially gamma-carboxylated Oc forms have hormonal function
      underscore the need for precise evaluation of Oc at all three potential gamma
      carboxylation sites. Herein, mass spectrometric immunoassay (MSIA) was used to
      provide qualitative and semiquantitative (relative percent abundance) information
      on Oc molecular variants as they exist in individual plasma and serum samples.
      Following verification that observable Oc proteoforms were accurately assigned
      and not simply ex vivo artifacts, MALDI-MSIA and ESI-MSIA were used to assess the
      relative abundance of Oc truncation and gamma-carboxylation, respectively, in
      plasma from 130 patients enrolled in vitamin K supplementation trials. Human Oc
      was found to circulate in over a dozen truncated forms with each of these
      displaying anywhere from 0-3 Gla residues. The relative abundance of truncated
      forms was consistent and unaffected by vitamin K supplementation. In contrast,
      when compared with placebo, vitamin K supplementation dramatically increased the
      fractional abundance of Oc with three Gla residues, corresponding to a decrease
      in the fractional abundance of Oc with zero Gla residues. These findings
      unequivocally document that increased vitamin K intake reduces the uncarboxylated
      form of Oc. Several reports of a positive effect of vitamin K intake on insulin
      sensitivity in humans have shown that un- or undercarboxylation of Oc, unlike in
      mice, is not associated with insulin resistance. Analyses similar to those
      described here will be useful to understand the functional significance of Oc
      gamma-carboxylation in human health and disease. 

PMID- 25855757
TI  - Screening urine samples for the absence of urinary tract infection using the
      sediMAX automated microscopy analyser.
AB  - Urinalysis culminates in a workload skew within the clinical microbiology
      laboratory. Routine processing involves screening via manual microscopy or
      biochemical dipstick measurement, followed by culture for each sample. Despite
      this, as many as 80% of specimens are reported as negative; thus, there is vast
      wastage of resources and time, as well as delayed turnaround time of results as
      numerous negative cultures fulfil their required incubation time. Automation
      provides the potential for streamlining sample screening by efficiently (>30%
      sample exclusion) and reliably [negative predictive value (NPV) >= 95%] ruling
      out those likely to be negative, whilst also reducing resource usage and hands-on
      time. The present study explored this idea by using the sediMAX automated
      microscopy urinalysis platform. We prospectively collected and processed 1411 non
      selected samples directly after routine laboratory processing. The results from
      this study showed multiple optimum cut-off values for microscopy. However,
      although optimum cut-off values permitted rule-out of 40.1% of specimens, an
      associated 87.5% NPV was lower than the acceptable limit of 95%. Sensitivity and
      specificity of leukocytes and bacteria in determining urinary tract infection was
      assessed by receiver operator characteristic curves with area under the curve
      values found to be 0.697 [95% confidence interval (CI): 0.665-0.729] and 0.587
      (95% CI: 0.551-0.623), respectively. We suggested that the sediMAX was not
      suitable for use as a rule-out screen prior to culture and further validation
      work must be carried out before routine use of the analyser.

PMID- 25855756
TI  - Richard's back: death, scoliosis and myth making.
AB  - The body of a mediaeval monarch was always under scrutiny, and Richard III's was
      no exception. In death, however, his body became subject to new forms of
      examination and interpretation: stripped naked after the battle of Bosworth, his
      corpse was carried to Leicester and exhibited before being buried. In 2012, it
      was rediscovered. The revelation that Richard suffered from scoliosis prompts
      this article to re-evaluate the historical sources about Richard's physique and
      his posthumous reputation. This article argues that Richard's death and his myth
      as 'crookback' are inextricably linked and traces attitudes to spinal curvature
      in the early modern period. It also considers how Shakespeare represented Richard
      as deformed, and aspects of performance history which suggest physical
      vulnerability. It then considers Richard's scoliosis from the perspective of
      medical history, reviewing classical accounts of scoliosis and arguing that
      Richard was probably treated with a mixture of axial traction and pressure. It
      demonstrates from the evidence of Richard's medical household that he was well
      placed to receive hands-on therapies and considers in particular the role of his
      physician and surgeon, William Hobbes. Finally, it shows how the case of Richard
      III demonstrates the close relationship between politics and medicine in the
      period and the contorted process of historical myth making. 

PMID- 25855754
TI  - Epigenetic Determinants of Erythropoiesis: Role of the Histone Methyltransferase
      SetD8 in Promoting Erythroid Cell Maturation and Survival.
AB  - Erythropoiesis, in which committed progenitor cells generate millions of
      erythrocytes daily, involves dramatic changes in the chromatin structure and
      transcriptome of erythroblasts, prior to their enucleation. While the involvement
      of the master-regulatory transcription factors GATA binding protein 1 (GATA-1)
      and GATA-2 in this process is established, the mechanistic contributions of many
      chromatin-modifying/remodeling enzymes in red cell biology remain enigmatic. We
      demonstrated that SetD8, a histone methyltransferase that catalyzes
      monomethylation of histone H4 at lysine 20 (H4K20me1), is a context-dependent
      GATA-1 corepressor in erythroid cells. To determine whether SetD8 controls
      erythroid maturation and/or function, we used a small hairpin RNA (shRNA)-based
      loss-of-function strategy in a primary murine erythroblast culture system. In
      this system, SetD8 promoted erythroblast maturation and survival, and this did
      not involve upregulation of the established regulator of erythroblast survival
      Bcl-x(L). SetD8 catalyzed H4K20me1 at a critical Gata2 cis element and restricted
      occupancy by an enhancer of Gata2 transcription, Scl/TAL1, thereby repressing
      Gata2 transcription. Elevating GATA-2 levels in erythroid precursors yielded a
      maturation block comparable to that induced by SetD8 downregulation. As lowering
      GATA-2 expression in the context of SetD8 knockdown did not rescue erythroid
      maturation, we propose that SetD8 regulation of erythroid maturation involves
      multiple target genes. These results establish SetD8 as a determinant of
      erythroid cell maturation and provide a framework for understanding how a broadly
      expressed histone-modifying enzyme mediates cell-type-specific GATA factor
      function.

PMID- 25855758
TI  - Reductions in virological failure and drug resistance in Chinese antiretroviral
      treated patients due to lamivudine-based regimens, 2003-12.
AB  - BACKGROUND: China's National Free Antiretroviral Treatment Program (NFATP) has
      significantly scaled up and standardized treatment since 2008. Meanwhile, no
      study worldwide has examined on a large scale the effects of rapid ART programme
      scale-up on treatment outcomes in resource-limited settings. METHODS: We used
      China's national HIV drug resistance (HIVDR) surveillance database to determine
      virological failure, acquired drug resistance and poor adherence rates after 12
      15 months of first-line ART. A total of 2252 patients were examined, with 1431
      patients having initiated ART before 2008 and 821 since 2008. FINDINGS: Since
      2008, virological failure at 12-15 months of treatment improved from 26.6% to
      12.1%, and HIVDR rates also significantly decreased from 15.4% to 5.4%. However,
      these successes are strongly associated with the standardized use of lamivudine
      based regimens in place of didanosine-based regimens. Patients who initiated
      lamivudine-based regimens before 2008 showed significant improvement in adherence
      [missed doses adjusted OR (AOR), 0.65; 95% CI, 0.45-0.96], virological failure
      (AOR, 0.29; 95% CI, 0.22-0.39) and HIVDR outcomes (AOR, 0.29; 95% CI, 0.20-0.42)
      compared with those who initiated didanosine-based regimens. Meanwhile, among
      only patients on lamivudine-based regimens, no significant changes were observed
      between those who initiated before 2008 and those who initiated since 2008.
      CONCLUSIONS: China's NFATP has been largely successful throughout the scale-up,
      with an overall reduction in virological failure and HIVDR. However, excluding
      the effect of lamivudine-based regimens, it remains crucial for the programme to
      improve patient adherence and quality of care, particularly in key vulnerable
      populations such as those infected through injecting drug or blood routes.

PMID- 25855759
TI  - The ever-evolving landscape of candidaemia in patients with acute leukaemia: non
      susceptibility to caspofungin and multidrug resistance are associated with
      increased mortality.
AB  - OBJECTIVES: The epidemiology and clinical course of candidaemia in patients with
      acute leukaemia, a population frequently exposed to antifungals, have not been
      extensively studied. In the present contemporary series of acute leukaemia
      patients, we describe patient characteristics, Candida species and MIC
      distributions and investigate the association between antifungal resistance and
      all-cause mortality. METHODS: We performed a retrospective review of medical
      records and microbiological data of adult patients with acute leukaemia or high
      risk myelodysplastic syndrome with at least one positive blood culture for
      Candida species at the MD Anderson Cancer Center between January 2008 and October
      2012. Susceptibility was defined according to the 2012 epidemiological cut-off
      values and clinical breakpoints. RESULTS: We identified 67 episodes of
      candidaemia in 65 patients. Almost all episodes (94%) occurred in patients who
      were receiving antifungal agents, 71% in patients receiving an echinocandin.
      Almost all isolates (99%) were of non-albicans Candida species [most frequently
      Candida parapsilosis (32%), Candida tropicalis (23%) and Candida glabrata (20%)].
      Caspofungin non-susceptibility was significantly associated with fluconazole
      resistance (P < 0.001). Non-susceptibility to caspofungin and multidrug
      resistance were associated with excess 14 day [adjusted HR (aHR) 3.02 (95% CI
      1.28-7.09), P = 0.011 and aHR 3.02 (95% CI 1.27-7.14), P = 0.012, respectively]
      and 30 day [aHR 2.96 (95% CI 1.38-6.37), P = 0.005 and aHR 2.86 (95% CI 1.31
      6.21), P = 0.008, respectively] all-cause mortality. CONCLUSIONS: In patients
      with acute leukaemia, a shift in candidaemia epidemiology was noted with a 99%
      predominance of non-albicans species. Non-susceptibility of Candida strains to
      caspofungin or multidrug resistance were independent markers of poor outcome in
      this patient population.

PMID- 25855760
TI  - First-line eradication rates comparing two shortened non-bismuth quadruple
      regimens against Helicobacter pylori: an open-label, randomized, multicentre
      clinical trial.
AB  - OBJECTIVES: Helicobacter pylori eradication remains a challenge. Non-bismuth
      based quadruple regimens (NBQR) have shown high eradication rates (ER) elsewhere
      that need to be locally confirmed. The objective of this study was to compare the
      first-line ER of a hybrid therapy (20 mg of omeprazole twice daily and 1 g of
      amoxicillin twice daily for 10 days, adding 500 mg of clarithromycin twice daily
      and 500 mg of metronidazole every 8 h for the last 5 days; OA-OACM) with that of
      a 10 day concomitant regimen consisting of taking all four drugs twice daily
      every day (including 500 mg of metronidazole every 12 h; OACM). A 10 day arm with
      standard triple therapy (OAC; 20 mg of omeprazole/12 h, 1 g of amoxicillin/12 h
      and 500 mg of clarithromycin/12 h) was included. PATIENTS AND METHODS: Three
      hundred consecutive patients were randomized (1: 2: 2) into one of the three
      following regimens: (i) OAC (60); (ii) OA-OACM (120); and (iii) OACM (120).
      Eradication was generally confirmed by a [(13)C]urea breath test at least 4 weeks
      after the end of treatment. Adverse events and compliance were assessed. EudraCT:
      2011-006258-99. RESULTS: ITT cure rates were: OAC, 70.0% (42/60) (95% CI: 58.3
      81.7); OA-OACM, 90.8% (109/120) (95% CI: 85.6-96.0); and OACM, 90.0% (107/119)
      (95% CI: 84.6-95.4). PP rates were: OAC, 72.4% (42/58) (95% CI: 60.8-84.1); OA
      OACM, 93.9% (108/115) (95% CI: 89.5-98.3); and OACM, 90.3% (102/113) (95% CI:
      84.8-95.8). Both NBQR significantly improved ER compared with OAC (P < 0.01), but
      no differences were seen between them. Mean compliance was elevated [98.0% (SD =
      9.8)] with no differences between groups. There were more adverse events in the
      quadruple arms (OACM, 65.8%; OA-OACM, 68.6%; OAC, 46.6%; P < 0.05), but no
      significant differences between groups in terms of severity were seen.
      CONCLUSIONS: Hybrid and concomitant regimens show good ER against H. pylori
      infection with an acceptable safety profile. They clearly displace OAC as first
      line regimen in our area.

PMID- 25855761
TI  - Nefopam Hydrochloride: A Fatal Overdose.
AB  - Nefopam is a non-opiate analgesic commonly used for the treatment of moderate to
      severe pain. A case of a 37-year-old male who was found dead in the morning is
      presented. An autopsy was performed and femoral venous blood, heart blood, urine,
      and vitreous humor were submitted for toxicological analysis. A general drug
      screen detected the presence of nefopam, caffeine, nicotine, citalopram,
      gabapentin, amitriptyline, diazepam and paracetamol in cardiac blood. Nefopam was
      quantitated by high-performance liquid chromatography with diode-array detection.
      Nefopam was found at the following concentrations: 13.6 mg/L in unpreserved
      femoral blood; 14.7 mg/L in preserved (fluoride-oxalate) femoral blood; 21.2 mg/L
      in unpreserved cardiac blood and 4.5 mg/L in preserved vitreous. Citalopram was
      present at a concentration of 0.7 mg/L (femoral blood) and 0.9 mg/L (cardiac
      blood). Ethanol analyzed by headspace gas chromatography (GC-FID) was detected in
      preserved (fluoride-oxalate) vitreous (14 mg/100 mL) and preserved (fluoride
      oxalate) urine 50 mg/100 mL. Death was attributed to atherosclerotic coronary
      artery disease and therapeutic drug toxicity. 

PMID- 25855762
TI  - Elastin degradation product isodesmosine is a chemoattractant for Pseudomonas
      aeruginosa.
AB  - Previous studies have demonstrated that Pseudomonas aeruginosa PAO1 is
      chemotactic towards proteinogenic amino acids, however, the chemotaxis response
      of this strain towards non-proteinogenic amino acids and the specific
      chemoreceptors involved in this response are essentially unknown. In this study,
      we analysed the chemotactic response of PAO1 towards two degradation products of
      elastin, the lysine-rich, non-proteinogenic amino acids, desmosine and
      isodesmosine. We observed that isodesmosine, a potential biomarker for different
      diseases, served as a chemoattractant for PAO1. A screen of 251methyl-accepting
      chemotaxis proteins mutants of PAO1 identified PctA as the chemoreceptor for
      isodesmosine. We also showed that the positive chemotactic response to
      isodesmosine is potentially common by demonstrating chemoattraction in 12 of 15
      diverse (in terms of source of isolation) clinical isolates, suggesting that the
      chemotactic response to this non-proteinogenic amino acid might be a conserved
      feature of acute infection isolates and thus could influence the colonization of
      potential infection sites. 

PMID- 25855764
TI  - Bacterial pneumonia in older people.

PMID- 25855763
TI  - High-affinity nitrate/nitrite transporters NrtA and NrtB of Aspergillus nidulans
      exhibit high specificity and different inhibitor sensitivity.
AB  - The NrtA and NrtB nitrate transporters are paralogous members of the major
      facilitator superfamily in Aspergillus nidulans. The availability of loss-of
      function mutations allowed individual investigation of the specificity and
      inhibitor sensitivity of both NrtA and NrtB. In this study, growth response tests
      were carried out at a growth-limiting concentration of nitrate (1 mM) as the sole
      nitrogen source, in the presence of a number of potential nitrate analogues at
      various concentrations, to evaluate their effect on nitrate transport. Both
      chlorate and chlorite inhibited fungal growth, with chlorite exerting the greater
      inhibition. The main transporter of nitrate, NrtA, proved to be more sensitive to
      chlorate than the minor transporter, NrtB. Similarly, the cation caesium was
      shown to exert differential effects, strongly inhibiting the activity of NrtB,
      but not NrtA. In contrast, no inhibition of nitrate uptake by NrtA or NrtB
      transporters was observed in either growth tests or uptake assays in the presence
      of bicarbonate, formate, malonate or oxalate (sulphite could not be tested in
      uptake assays owing to its reaction with nitrate), indicating significant
      specificity of nitrate transport. Kinetic analyses of nitrate uptake revealed
      that both chlorate and chlorite inhibited NrtA competitively, while these same
      inhibitors inhibited NrtB in a non-competitive fashion. The caesium ion appeared
      to inhibit NrtA in a non-competitive fashion, while NrtB was inhibited
      uncompetitively. The results provide further evidence of the distinctly different
      characteristics as well as the high specificity of nitrate uptake by these two
      transporters.

PMID- 25855771
TI  - Thioredoxin-Interacting Protein Deficiency Protects against Diabetic Nephropathy.
AB  - Expression of thioredoxin-interacting protein (TxNIP), an endogenous inhibitor of
      the thiol oxidoreductase thioredoxin, is augmented by high glucose (HG) and
      promotes oxidative stress. We previously reported that TxNIP-deficient mesangial
      cells showed protection from HG-induced reactive oxygen species, mitogen
      activated protein kinase phosphorylation, and collagen expression. Here, we
      investigated the potential role of TxNIP in the pathogenesis of diabetic
      nephropathy (DN) in vivo. Wild-type (WT) control, TxNIP(-/-), and TxNIP(+/-) mice
      were rendered equally diabetic with low-dose streptozotocin. In contrast to
      effects in WT mice, diabetes did not increase albuminuria, proteinuria, serum
      cystatin C, or serum creatinine levels in TxNIP(-/-) mice. Whereas morphometric
      studies of kidneys revealed a thickened glomerular basement membrane and effaced
      podocytes in the diabetic WT mice, these changes were absent in the diabetic
      TxNIP(-/-) mice. Immunohistochemical analysis revealed significant increases in
      the levels of glomerular TGF-beta1, collagen IV, and fibrosis only in WT diabetic
      mice. Additionally, only WT diabetic mice showed significant increases in
      oxidative stress (nitrotyrosine, urinary 8-hydroxy-2-deoxy-guanosine) and
      inflammation (IL-1beta mRNA, F4/80 immunohistochemistry). Expression levels of
      Nox4-encoded mRNA and protein increased only in the diabetic WT animals. A
      significant loss of podocytes, assessed by Wilms' tumor 1 and nephrin staining
      and urinary nephrin concentration, was found in diabetic WT but not TxNIP(-/-)
      mice. Furthermore, in cultured human podocytes exposed to HG, TxNIP knockdown
      with siRNA abolished the increased mitochondrial O2 (-) generation and apoptosis.
      These data indicate that TxNIP has a critical role in the progression of DN and
      may be a promising therapeutic target. 

PMID- 25855772
TI  - Rehospitalizations and Emergency Department Visits after Hospital Discharge in
      Patients Receiving Maintenance Hemodialysis.
AB  - Clinical outcomes after a hospital discharge are poorly defined for patients
      receiving maintenance in-center (outpatient) hemodialysis. To describe the
      proportion and characteristics of these patients who are rehospitalized, visit an
      emergency department, or die within 30 days after discharge from an acute
      hospitalization, we conducted a population-based study of all adult patients
      receiving maintenance in-center hemodialysis who were discharged between January
      1, 2003, and December 31, 2011, from 157 acute care hospitals in Ontario, Canada.
      For patients with more than one hospitalization, we randomly selected a single
      hospitalization as the index hospitalization. Of the 11,177 patients included in
      the final cohort, 1926 (17%) were rehospitalized, 2971 (27%) were treated in the
      emergency department, and 840 (7.5%) died within 30 days of discharge.
      Complications of type 2 diabetes mellitus were the most common reason for
      rehospitalization, whereas heart failure was the most common reason for an
      emergency department visit. In multivariable analysis using a cause-specific Cox
      proportional hazards model, the following characteristics were associated with 30
      day rehospitalization: older age, the number of hospital admissions in the
      preceding 6 months, the number of emergency department visits in the preceding 6
      months, higher Charlson comorbidity index score, and the receipt of mechanical
      ventilation during the index hospitalization. Thus, a large proportion of
      patients receiving maintenance in-center hemodialysis will be readmitted or visit
      an emergency room within 30 days of an acute hospitalization. A focus on
      improving care transitions from the inpatient setting to the outpatient dialysis
      unit may improve outcomes and reduce healthcare costs. 

PMID- 25855773
TI  - Dendritic Cells in Kidney Transplant Biopsy Samples Are Associated with T Cell
      Infiltration and Poor Allograft Survival.
AB  - Progress in long-term renal allograft survival continues to lag behind the
      progress in short-term transplant outcomes. Dendritic cells are the most
      efficient antigen-presenting cells, but surprisingly little attention has been
      paid to their presence in transplanted kidneys. We used dendritic cell-specific
      intercellular adhesion molecule-3-grabbing nonintegrin as a marker of dendritic
      cells in 105 allograft biopsy samples from 105 kidney transplant recipients. High
      dendritic cell density was associated with poor allograft survival independent of
      clinical variables. Moreover, high dendritic cell density correlated with greater
      T cell proliferation and poor outcomes in patients with high total inflammation
      scores, including inflammation in areas of tubular atrophy. We then explored the
      association between dendritic cells and histologic variables associated with poor
      prognosis. Multivariate analysis revealed an independent association between the
      densities of dendritic cells and T cells. In biopsy samples with high dendritic
      cell density, electron microscopy showed direct physical contact between
      infiltrating lymphocytes and cells that have the ultrastructural morphologic
      characteristics of dendritic cells. The origin of graft dendritic cells was
      sought in nine sex-mismatched recipients using XY fluorescence in situ
      hybridization. Whereas donor dendritic cells predominated initially, the majority
      of dendritic cells in late allograft biopsy samples were of recipient origin. Our
      data highlight the prognostic value of dendritic cell density in allograft biopsy
      samples, suggest a new role for these cells in shaping graft inflammation, and
      provide a rationale for targeting dendritic cell recruitment to promote long-term
      allograft survival. 

PMID- 25855774
TI  - Disease Severity Correlates with Thrombotic Capacity in Experimental Nephrotic
      Syndrome.
AB  - Thrombotic disease, a major life-threatening complication of nephrotic syndrome,
      has been associated with proteinuria and hypoalbuminemia severity. However, it is
      not fully understood how disease severity correlates with severity of the
      acquired hypercoagulopathy of nephrotic syndrome. Without this knowledge, the
      utility of proteinuria and/or hypoalbuminemia as biomarkers of thrombotic risk
      remains limited. Here, we show that two well established ex vivo
      hypercoagulopathy assays, thrombin generation and rotational thromboelastometry,
      are highly correlated with proteinuria and hypoalbuminemia in the puromycin
      aminonucleoside and adriamycin rat models of nephrotic syndrome. Notably, in the
      puromycin aminonucleoside model, hyperfibrinogenemia and antithrombin deficiency
      were also correlated with proteinuria severity, consistent with reports in human
      nephrotic syndrome. Importantly, although coagulation was not spontaneously
      activated in vivo with increasing proteinuria, vascular injury induced a more
      robust thrombotic response in nephrotic animals. In conclusion, hypercoagulopathy
      is highly correlated with nephrotic disease severity, but overt thrombosis may
      require an initiating insult, such as vascular injury. Our results suggest that
      proteinuria and/or hypoalbuminemia could be developed as clinically meaningful
      surrogate biomarkers of hypercoagulopathy to identify patients with nephrotic
      syndrome at highest risk for thrombotic disease and potentially target them for
      anticoagulant pharmacoprophylaxis.

PMID- 25855775
TI  - Plasma IL-6 and IL-10 Concentrations Predict AKI and Long-Term Mortality in
      Adults after Cardiac Surgery.
AB  - Inflammation has an integral role in the pathophysiology of AKI. We investigated
      the associations of two biomarkers of inflammation, plasma IL-6 and IL-10, with
      AKI and mortality in adults undergoing cardiac surgery. Patients were enrolled at
      six academic centers (n = 960). AKI was defined as a >= 50% or >= 0.3-mg/dl
      increase in serum creatinine from baseline. Pre- and postoperative IL-6 and IL-10
      concentrations were categorized into tertiles and evaluated for associations with
      outcomes of in-hospital AKI or postdischarge all-cause mortality at a median of 3
      years after surgery. Preoperative concentrations of IL-6 and IL-10 were not
      significantly associated with AKI or mortality. Elevated first postoperative IL-6
      concentration was significantly associated with higher risk of AKI, and the risk
      increased in a dose-dependent manner (second tertile adjusted odds ratio [OR],
      1.61 [95% confidence interval (95% CI), 1.10 to 2.36]; third tertile adjusted OR,
      2.13 [95% CI, 1.45 to 3.13]). First postoperative IL-6 concentration was not
      associated with risk of mortality; however, the second tertile of peak IL-6
      concentration was significantly associated with lower risk of mortality (adjusted
      hazard ratio, 0.75 [95% CI, 0.57 to 0.99]). Elevated first postoperative IL-10
      concentration was significantly associated with higher risk of AKI (adjusted OR,
      1.57 [95% CI, 1.04 to 2.38]) and lower risk of mortality (adjusted HR, 0.72 [95%
      CI, 0.56 to 0.93]). There was a significant interaction between the concentration
      of neutrophil gelatinase-associated lipocalin, an established AKI biomarker, and
      the association of IL-10 concentration with mortality (P = 0.01). These findings
      suggest plasma IL-6 and IL-10 may serve as biomarkers for perioperative outcomes.

PMID- 25855776
TI  - Four-and-a-Half LIM Domains Protein 2 Is a Coactivator of Wnt Signaling in
      Diabetic Kidney Disease.
AB  - Diabetic kidney disease (DKD) is a microvascular complication that leads to
      kidney dysfunction and ESRD, but the underlying mechanisms remain unclear.
      Podocyte Wnt-pathway activation has been demonstrated to be a trigger mechanism
      for various proteinuric diseases. Notably, four-and-a-half LIM domains protein 2
      (FHL2) is highly expressed in urogenital systems and has been implicated in
      Wnt/beta-catenin signaling. Here, we used in vitro podocyte culture experiments
      and a streptozotocin-induced DKD model in FHL2 gene-knockout mice to determine
      the possible role of FHL2 in DKD and to clarify its association with the Wnt
      pathway. In human and mouse kidney tissues, FHL2 protein was abundantly expressed
      in podocytes but not in renal tubular cells. Treatment with high glucose or
      diabetes-related cytokines, including angiotensin II and TGF-beta1, activated
      FHL2 protein and Wnt/beta-catenin signaling in cultured podocytes. This
      activation also upregulated FHL2 expression and promoted FHL2 translocation from
      cytosol to nucleus. Genetic deletion of the FHL2 gene mitigated the podocyte
      dedifferentiation caused by activated Wnt/beta-catenin signaling under Wnt-On,
      but not under Wnt-Off, conditions. Diabetic FHL2(+/+) mice developed markedly
      increased albuminuria and thickening of the glomerular basement membrane compared
      with nondiabetic FHL2(+/+) mice. However, FHL2 knockout significantly attenuated
      these DKD-induced changes. Furthermore, kidney samples from patients with
      diabetes had a higher degree of FHL2 podocyte nuclear translocation, which was
      positively associated with albuminuria and progressive renal function
      deterioration. Therefore, we conclude that FHL2 has both structural and
      functional protein-protein interactions with beta-catenin in the podocyte nucleus
      and that FHL2 protein inhibition can mitigate Wnt/beta-catenin-induced
      podocytopathy. 

PMID- 25855777
TI  - Effect of Potassium Citrate on Calcium Phosphate Stones in a Model of
      Hypercalciuria.
AB  - Potassium citrate is prescribed to decrease stone recurrence in patients with
      calcium nephrolithiasis. Citrate binds intestinal and urine calcium and increases
      urine pH. Citrate, metabolized to bicarbonate, should decrease calcium excretion
      by reducing bone resorption and increasing renal calcium reabsorption. However,
      citrate binding to intestinal calcium may increase absorption and renal excretion
      of both phosphate and oxalate. Thus, the effect of potassium citrate on urine
      calcium oxalate and calcium phosphate supersaturation and stone formation is
      complex and difficult to predict. To study the effects of potassium citrate on
      urine supersaturation and stone formation, we utilized 95th-generation inbred
      genetic hypercalciuric stone-forming rats. Rats were fed a fixed amount of a
      normal calcium (1.2%) diet supplemented with potassium citrate or potassium
      chloride (each 4 mmol/d) for 18 weeks. Urine was collected at 6, 12, and 18
      weeks. At 18 weeks, stone formation was visualized by radiography. Urine citrate,
      phosphate, oxalate, and pH levels were higher and urine calcium level was lower
      in rats fed potassium citrate. Furthermore, calcium oxalate and calcium phosphate
      supersaturation were higher with potassium citrate; however, uric acid
      supersaturation was lower. Both groups had similar numbers of exclusively calcium
      phosphate stones. Thus, potassium citrate effectively raises urine citrate levels
      and lowers urine calcium levels; however, the increases in urine pH, oxalate, and
      phosphate levels lead to increased calcium oxalate and calcium phosphate
      supersaturation. Potassium citrate induces complex changes in urine chemistries
      and resultant supersaturation, which may not be beneficial in preventing calcium
      phosphate stone formation. 

PMID- 25855778
TI  - Vascular Type 1A Angiotensin II Receptors Control BP by Regulating Renal Blood
      Flow and Urinary Sodium Excretion.
AB  - Inappropriate activation of the type 1A angiotensin (AT1A) receptor contributes
      to the pathogenesis of hypertension and its associated complications. To define
      the role for actions of vascular AT1A receptors in BP regulation and hypertension
      pathogenesis, we generated mice with cell-specific deletion of AT1A receptors in
      smooth muscle cells (SMKO mice) using Loxp technology and Cre transgenes with
      robust expression in both conductance and resistance arteries. We found that
      elimination of AT1A receptors from vascular smooth muscle cells (VSMCs) caused a
      modest (approximately 7 mmHg) yet significant reduction in baseline BP and
      exaggerated sodium sensitivity in mice. Additionally, the severity of angiotensin
      II (Ang II)-dependent hypertension was dramatically attenuated in SMKO mice, and
      this protection against hypertension was associated with enhanced urinary
      excretion of sodium. Despite the lower BP, acute vasoconstrictor responses to Ang
      II in the systemic vasculature were largely preserved (approximately 80% of
      control levels) in SMKO mice because of exaggerated activity of the sympathetic
      nervous system rather than residual actions of AT1B receptors. In contrast, Ang
      II-dependent responses in the renal circulation were almost completely eliminated
      in SMKO mice (approximately 5%-10% of control levels). These findings suggest
      that direct actions of AT1A receptors in VSMCs are essential for regulation of
      renal blood flow by Ang II and highlight the capacity of Ang II-dependent
      vascular responses in the kidney to effect natriuresis and BP control. 

PMID- 25855779
TI  - Reduced Renal Methylarginine Metabolism Protects against Progressive Kidney
      Damage.
AB  - Nitric oxide (NO) production is diminished in many patients with cardiovascular
      and renal disease. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor
      of NO synthesis, and elevated plasma levels of ADMA are associated with poor
      outcomes. Dimethylarginine dimethylaminohydrolase-1 (DDAH1) is a methylarginine
      metabolizing enzyme that reduces ADMA levels. We reported previously that a DDAH1
      gene variant associated with increased renal DDAH1 mRNA transcription and lower
      plasma ADMA levels, but counterintuitively, a steeper rate of renal function
      decline. Here, we test the hypothesis that reduced renal-specific ADMA metabolism
      protects against progressive renal damage. Renal DDAH1 is expressed predominately
      within the proximal tubule. A novel proximal tubule-specific Ddah1 knockout
      (Ddah1(PT-/-)) mouse demonstrated tubular cell accumulation of ADMA and lower NO
      concentrations, but unaltered plasma ADMA concentrations. Ddah1(PT-/-) mice were
      protected from reduced kidney tissue mass, collagen deposition, and profibrotic
      cytokine expression in two independent renal injury models: folate nephropathy
      and unilateral ureteric obstruction. Furthermore, a study of two independent
      kidney transplant cohorts revealed higher levels of human renal allograft
      methylarginine-metabolizing enzyme gene expression associated with steeper
      function decline. We also report an association among DDAH1 expression, NO
      activity, and uromodulin expression supported by data from both animal and human
      studies, raising the possibility that kidney DDAH1 expression exacerbates renal
      injury through uromodulin-related mechanisms. Together, these data demonstrate
      that reduced renal tubular ADMA metabolism protects against progressive kidney
      function decline. Thus, circulating ADMA may be an imprecise marker of renal
      methylarginine metabolism, and therapeutic ADMA reduction may even be deleterious
      to kidney function. 

PMID- 25855780
TI  - P2Y12 Receptor Localizes in the Renal Collecting Duct and Its Blockade Augments
      Arginine Vasopressin Action and Alleviates Nephrogenic Diabetes Insipidus.
AB  - P2Y12 receptor (P2Y12-R) signaling is mediated through Gi, ultimately reducing
      cellular cAMP levels. Because cAMP is a central modulator of arginine vasopressin
      (AVP)-induced water transport in the renal collecting duct (CD), we hypothesized
      that if expressed in the CD, P2Y12-R may play a role in renal handling of water
      in health and in nephrogenic diabetes insipidus. We found P2Y12-R mRNA expression
      in rat kidney, and immunolocalized its protein and aquaporin-2 (AQP2) in CD
      principal cells. Administration of clopidogrel bisulfate, an irreversible
      inhibitor of P2Y12-R, significantly increased urine concentration and AQP2
      protein in the kidneys of Sprague-Dawley rats. Notably, clopidogrel did not alter
      urine concentration in Brattleboro rats that lack AVP. Clopidogrel administration
      also significantly ameliorated lithium-induced polyuria, improved urine
      concentrating ability and AQP2 protein abundance, and reversed the lithium
      induced increase in free-water excretion, without decreasing blood or kidney
      tissue lithium levels. Clopidogrel administration also augmented the lithium
      induced increase in urinary AVP excretion and suppressed the lithium-induced
      increase in urinary nitrates/nitrites (nitric oxide production) and 8-isoprostane
      (oxidative stress). Furthermore, selective blockade of P2Y12-R by the reversible
      antagonist PSB-0739 in primary cultures of rat inner medullary CD cells
      potentiated the expression of AQP2 and AQP3 mRNA, and cAMP production induced by
      dDAVP (desmopressin). In conclusion, pharmacologic blockade of renal P2Y12-R
      increases urinary concentrating ability by augmenting the effect of AVP on the
      kidney and ameliorates lithium-induced NDI by potentiating the action of AVP on
      the CD. This strategy may offer a novel and effective therapy for lithium-induced
      NDI. 

PMID- 25855781
TI  - Reduction of Tubular Flow Rate as a Mechanism of Oliguria in the Early Phase of
      Endotoxemia Revealed by Intravital Imaging.
AB  - Urine output is widely used as a criterion for the diagnosis of AKI. Although
      several potential mechanisms of septic AKI have been identified, regulation of
      urine flow after glomerular filtration has not been evaluated. This study
      evaluated changes in urine flow in mice with septic AKI. The intratubular urine
      flow rate was monitored in real time by intravital imaging using two-photon laser
      microscopy. The tubular flow rate, as measured by freely filtered dye (FITC
      inulin or Lucifer yellow), time-dependently declined after LPS injection. At 2
      hours, the tubular flow rate was slower in mice injected with LPS than in mice
      injected with saline, whereas BP and GFR were similar in the two groups.
      Importantly, fluorophore-conjugated LPS selectively accumulated in the proximal
      tubules that showed reduced tubular flow at 2 hours and luminal obstruction with
      cell swelling at 24 hours. Delipidation of LPS or deletion of Toll-like receptor
      4 in mice abolished these effects, whereas neutralization of TNF-alpha had little
      effect on LPS-induced tubular flow retention. Rapid intravenous fluid
      resuscitation within 6 hours improved the tubular flow rate only when accompanied
      by the dilation of obstructed proximal tubules with accumulated LPS. These
      findings suggest that LPS reduces the intratubular urine flow rate during early
      phases of endotoxemia through a Toll-like receptor 4-dependent mechanism, and
      that the efficacy of fluid resuscitation may depend on the response of tubules
      with LPS accumulation. 

PMID- 25855782
TI  - Outcomes of Elderly Patients after Predialysis Vascular Access Creation.
AB  - Uniform vascular access guidelines for elderly patients may be inappropriate
      because of the competing risk of death, high rate of arteriovenous fistula (AVF)
      maturation failure, and poor vascular access outcomes in this population.
      However, the outcomes in elderly patients with advanced CKD who receive permanent
      vascular access before dialysis initiation are unclear. We identified a large
      nationally representative cohort of 3418 elderly patients (aged >= 70 years) with
      CKD undergoing predialysis AVF or arteriovenous graft (AVG) creation from 2004 to
      2009, and assessed the frequencies of dialysis initiation, death before dialysis
      initiation, and dialysis-free survival for 2 years after vascular access
      creation. In all, 67% of patients with predialysis AVF and 71% of patients with
      predialysis AVG creation initiated dialysis within 2 years of access placement,
      but the overall risk of dialysis initiation was modified by patient age and race.
      Only one half of patients initiated dialysis with a functioning AVF or AVG; 46.8%
      of AVFs were created <90 days before dialysis initiation. Catheter dependence at
      dialysis initiation was more common in patients receiving predialysis AVF than in
      patients receiving AVG (46.0% versus 28.5%; P<0.001). In conclusion, most elderly
      patients with advanced CKD who received predialysis vascular access creation
      initiated dialysis within 2 years. As a consequence of late predialysis placement
      or maturation failure, almost one half of patients receiving AVFs initiated
      dialysis with a catheter. Insertion of an AVG closer to dialysis initiation may
      serve as a "catheter-sparing" approach and allow delay of permanent access
      placement in selected elderly patients with CKD.

PMID- 25855783
TI  - Inbreeding Affects Gene Expression Differently in Two Self-Incompatible
      Arabidopsis lyrata Populations with Similar Levels of Inbreeding Depression.
AB  - Knowledge of which genes and pathways are affected by inbreeding may help
      understanding the genetic basis of inbreeding depression, the potential for
      purging (selection against deleterious recessive alleles), and the transition
      from outcrossing to selfing. Arabidopsis lyrata is a predominantly self
      incompatible perennial plant, closely related to the selfing model species A.
      thaliana. To examine how inbreeding affects gene expression, we compared the
      transcriptome of experimentally selfed and outcrossed A. lyrata originating from
      two Scandinavian populations that express similar inbreeding depression for
      fitness (? ~ 0.80). The number of genes significantly differentially expressed
      between selfed and outcrossed individuals were 2.5 times higher in the Norwegian
      population (~ 500 genes) than in the Swedish population (~ 200 genes). In both
      populations, a majority of genes were upregulated on selfing (~ 80%). Functional
      annotation analysis of the differentially expressed genes showed that selfed
      offspring were characterized by 1) upregulation of stress-related genes in both
      populations and 2) upregulation of photosynthesis-related genes in Sweden but
      downregulation in Norway. Moreover, we found that reproduction- and pollination
      related genes were affected by inbreeding only in Norway. We conclude that
      inbreeding causes both general and population-specific effects. The observed
      common effects suggest that inbreeding generally upregulates rather than
      downregulates gene expression and affects genes associated with stress response
      and general metabolic activity. Population differences in the number of affected
      genes and in effects on the expression of photosynthesis-related genes show that
      the genetic basis of inbreeding depression can differ between populations with
      very similar levels of inbreeding depression.

PMID- 25855784
TI  - Addressing the social determinants of inequities in physical activity and
      sedentary behaviours.
AB  - Participation in both physical activity and sedentary behaviours follow a social
      gradient, such that those who are more advantaged are more likely to be regularly
      physically active, less likely to be sedentary, and less likely to experience the
      adverse health outcomes associated with inactive lifestyles than their less
      advantaged peers. The aim of this paper is to provide, in a format that will
      support policymakers and practitioners, an overview of the current evidence base
      and highlight promising approaches for promoting physical activity and reducing
      sedentary behaviours equitably at each level of 'Fair Foundations: The VicHealth
      framework for health equity'. A rapid review was undertaken in February-April
      2014. Electronic databases (Medline, PsychINFO, SportsDISCUS, CINAHL, Scopus, Web
      of Science, Cochrane Library, Global Health and Embase) were searched using a pre
      defined search strategy and grey literature searches of websites of key relevant
      organizations were undertaken. The majority of included studies focussed on
      approaches targeting behaviour change at the individual level, with fewer
      focussing on daily living conditions or broader socioeconomic, political and
      cultural contexts. While many gaps in the evidence base remain, particularly in
      relation to reducing sedentary behaviour, promising approaches for promoting
      physical activity equitably across the three levels of the Fair Foundations
      framework include: community-wide approaches; support for local and state
      governments to develop policies and practices; neighbourhood designs (including
      parks) that are conducive to physical activity; investment in early childhood
      interventions; school programmes; peer- or group-based programmes; and targeted
      motivational, cognitive-behavioural, and/or mediated individual-level approaches.

PMID- 25855786
TI  - CC-223, a Potent and Selective Inhibitor of mTOR Kinase: In Vitro and In Vivo
      Characterization.
AB  - mTOR is a serine/threonine kinase that regulates cell growth, metabolism,
      proliferation, and survival. mTOR complex-1 (mTORC1) and mTOR complex-2 (mTORC2)
      are critical mediators of the PI3K-AKT pathway, which is frequently mutated in
      many cancers, leading to hyperactivation of mTOR signaling. Although rapamycin
      analogues, allosteric inhibitors that target only the mTORC1 complex, have shown
      some clinical activity, it is hypothesized that mTOR kinase inhibitors, blocking
      both mTORC1 and mTORC2 signaling, will have expanded therapeutic potential. Here,
      we describe the preclinical characterization of CC-223. CC-223 is a potent,
      selective, and orally bioavailable inhibitor of mTOR kinase, demonstrating
      inhibition of mTORC1 (pS6RP and p4EBP1) and mTORC2 [pAKT(S473)] in cellular
      systems. Growth inhibitory activity was demonstrated in hematologic and solid
      tumor cell lines. mTOR kinase inhibition in cells, by CC-223, resulted in more
      complete inhibition of the mTOR pathway biomarkers and improved antiproliferative
      activity as compared with rapamycin. Growth inhibitory activity and apoptosis was
      demonstrated in a panel of hematologic cancer cell lines. Correlative analysis
      revealed that IRF4 expression level associates with resistance, whereas mTOR
      pathway activation seems to associate with sensitivity. Treatment with CC-223
      afforded in vivo tumor biomarker inhibition in tumor-bearing mice, after a single
      oral dose. CC-223 exhibited dose-dependent tumor growth inhibition in multiple
      solid tumor xenografts. Significant inhibition of mTOR pathway markers pS6RP and
      pAKT in CC-223-treated tumors suggests that the observed antitumor activity of CC
      223 was mediated through inhibition of both mTORC1 and mTORC2. CC-223 is
      currently in phase I clinical trials.

PMID- 25855785
TI  - Circadian Clock Gene CRY2 Degradation Is Involved in Chemoresistance of
      Colorectal Cancer.
AB  - Biomarkers for predicting chemotherapy response are important to the treatment of
      colorectal cancer patients. Cryptochrome 2 (CRY2) is a circadian clock protein
      involved in cell cycle, but the biologic consequences of this activity in cancer
      are poorly understood. We set up biochemical and cell biology analyses to analyze
      CRY2 expression and chemoresistance. Here, we report that CRY2 is overexpressed
      in chemoresistant colorectal cancer samples, and CRY2 overexpression is
      correlated with poor patient survival. Knockdown of CRY2 increased colorectal
      cancer sensitivity to oxaliplatin in colorectal cancer cells. We also identify
      FBXW7 as a novel E3 ubiquitin ligase for targeting CRY2 through proteasomal
      degradation. Mechanistic studies show that CRY2 is regulated by FBXW7, in which
      FBXW7 binds directly to phosphorylated Thr300 of CRY2. Furthermore, FBXW7
      expression leads to degradation of CRY2 through enhancing CRY2 ubiquitination and
      accelerating the CRY2's turnover rate. High FBXW7 expression downregulates CRY2
      and increases colorectal cancer cells' sensitivity to chemotherapy. Low FBXW7
      expression is correlated with high CRY2 expression in colorectal cancer patient
      samples. Also, low FBXW7 expression is correlated with poor patient survival.
      Taken together, our findings indicate that the upregulation of CRY2 caused by
      downregulation of FBXW7 may be a novel prognostic biomarker and may represent a
      new therapeutic target in colorectal cancer.

PMID- 25855787
TI  - The Link between Inactivation and High-Affinity Block of hERG1 Channels.
AB  - Block of human ether-a-go-go-related gene 1 (hERG1) K(+) channels by many drugs
      delays cardiac repolarization, prolongs QT interval, and is associated with an
      increased risk of cardiac arrhythmia. Preferential block of hERG1 channels in an
      inactivated state has been assumed because inactivation deficient mutant channels
      can exhibit dramatically reduced drug sensitivity. Here we reexamine the link
      between inactivation gating and potency of channel block using concatenated hERG1
      tetramers containing a variable number (0-4) of subunits harboring a point
      mutation (S620T or S631A) that disrupts inactivation. Concatenated hERG1
      tetramers containing four wild-type subunits exhibited high-affinity block by
      cisapride, dofetilide, and MK-499, similar to wild-type channels formed from
      hERG1 monomers. A single S620T subunit within a tetramer was sufficient to fully
      disrupt inactivation gating, whereas S631A suppressed inactivation as a graded
      function of the number of mutant subunits present in a concatenated tetramer.
      Drug potency was positively correlated to the number of S620T subunits contained
      within a tetramer but unrelated to mutation-induced disruption of channel
      inactivation. Introduction of a second point mutation (Y652W) into S620T hERG1
      partially rescued drug sensitivity. The potency of cisapride was not altered for
      tetramers containing 0 to 3 S631A subunits, whereas the potency of dofetilide was
      a graded function of the number of S631A subunits contained within a tetramer.
      Together these findings indicate that S620T or S631A substitutions can
      allosterically disrupt drug binding by a mechanism that is independent of their
      effects on inactivation gating. 

PMID- 25855788
TI  - Cell-surface Attachment of Bacterial Multienzyme Complexes Involves Highly
      Dynamic Protein-Protein Anchors.
AB  - Protein-protein interactions play a pivotal role in the assembly of the
      cellulosome, one of nature's most intricate nanomachines dedicated to the
      depolymerization of complex carbohydrates. The integration of cellulosomal
      components usually occurs through the binding of type I dockerin modules located
      at the C terminus of the enzymes to cohesin modules located in the primary
      scaffoldin subunit. Cellulosomes are typically recruited to the cell surface via
      type II cohesin-dockerin interactions established between primary and cell
      surface anchoring scaffoldin subunits. In contrast with type II interactions,
      type I dockerins usually display a dual binding mode that may allow increased
      conformational flexibility during cellulosome assembly. Acetivibrio
      cellulolyticus produces a highly complex cellulosome comprising an unusual
      adaptor scaffoldin, ScaB, which mediates the interaction between the primary
      scaffoldin, ScaA, through type II cohesin-dockerin interactions and the anchoring
      scaffoldin, ScaC, via type I cohesin-dockerin interactions. Here, we report the
      crystal structure of the type I ScaB dockerin in complex with a type I ScaC
      cohesin in two distinct orientations. The data show that the ScaB dockerin
      displays structural symmetry, reflected by the presence of two essentially
      identical binding surfaces. The complex interface is more extensive than those
      observed in other type I complexes, which results in an ultra-high affinity
      interaction (Ka ~10(12) M). A subset of ScaB dockerin residues was also
      identified as modulating the specificity of type I cohesin-dockerin interactions
      in A. cellulolyticus. This report reveals that recruitment of cellulosomes onto
      the cell surface may involve dockerins presenting a dual binding mode to
      incorporate additional flexibility into the quaternary structure of highly
      populated multienzyme complexes.

PMID- 25855789
TI  - Receptors, ion channels, and signaling mechanisms underlying microglial dynamics.
AB  - Microglia, the innate immune cells of the CNS, play a pivotal role in brain
      injury and disease. Microglia are extremely motile; their highly ramified
      processes constantly survey the brain parenchyma, and they respond promptly to
      brain damage with targeted process movement toward the injury site. Microglia
      play a key role in brain development and function by pruning synapses during
      development, phagocytosing apoptotic newborn neurons, and regulating neuronal
      activity by direct microglia-neuron or indirect microglia-astrocyte-neuron
      interactions, which all depend on their process motility. This review highlights
      recent discoveries about microglial dynamics, focusing on the receptors, ion
      channels, and signaling pathways involved. 

PMID- 25855791
TI  - Human Cytochrome P450 21A2, the Major Steroid 21-Hydroxylase: STRUCTURE OF THE
      ENZYME.PROGESTERONE SUBSTRATE COMPLEX AND RATE-LIMITING C-H BOND CLEAVAGE.
AB  - Cytochrome P450 (P450) 21A2 is the major steroid 21-hydroxylase, and deficiency
      of this enzyme is involved in ~95% of cases of human congenital adrenal
      hyperplasia, a disorder of adrenal steroidogenesis. A structure of the bovine
      enzyme that we published previously (Zhao, B., Lei, L., Kagawa, N.,
      Sundaramoorthy, M., Banerjee, S., Nagy, L. D., Guengerich, F. P., and Waterman,
      M. R. (2012) Three-dimensional structure of steroid 21-hydroxylase (cytochrome
      P450 21A2) with two substrates reveals locations of disease-associated variants.
      J. Biol. Chem. 287, 10613-10622), containing two molecules of the substrate
      17alpha-hydroxyprogesterone, has been used as a template for understanding
      genetic deficiencies. We have now obtained a crystal structure of human P450 21A2
      in complex with progesterone, a substrate in adrenal 21-hydroxylation. Substrate
      binding and release were fast for human P450 21A2 with both substrates, and pre
      steady-state kinetics showed a partial burst but only with progesterone as
      substrate and not 17alpha-hydroxyprogesterone. High intermolecular non
      competitive kinetic deuterium isotope effects on both kcat and kcat/Km, from 5 to
      11, were observed with both substrates, indicative of rate-limiting C-H bond
      cleavage and suggesting that the juxtaposition of the C21 carbon in the active
      site is critical for efficient oxidation. The estimated rate of binding of the
      substrate progesterone (kon 2.4 * 10(7) M(-1) s(-1)) is only ~2-fold greater than
      the catalytic efficiency (kcat/Km = 1.3 * 10(7) M(-1) s(-1)) with this substrate,
      suggesting that the rate of substrate binding may also be partially rate
      limiting. The structure of the human P450 21A2-substrate complex provides direct
      insight into mechanistic effects of genetic variants.

PMID- 25855790
TI  - The Biosynthesis of Capuramycin-type Antibiotics: IDENTIFICATION OF THE A-102395
      BIOSYNTHETIC GENE CLUSTER, MECHANISM OF SELF-RESISTANCE, AND FORMATION OF URIDINE
      5'-CARBOXAMIDE.
AB  - A-500359s, A-503083s, and A-102395 are capuramycin-type nucleoside antibiotics
      that were discovered using a screen to identify inhibitors of bacterial
      translocase I, an essential enzyme in peptidoglycan cell wall biosynthesis. Like
      the parent capuramycin, A-500359s and A-503083s consist of three structural
      components: a uridine-5'-carboxamide (CarU), a rare unsaturated hexuronic acid,
      and an aminocaprolactam, the last of which is substituted by an unusual arylamine
      containing polyamide in A-102395. The biosynthetic gene clusters for A-500359s
      and A-503083s have been reported, and two genes encoding a putative non-heme
      Fe(II)-dependent alpha-ketoglutarate:UMP dioxygenase and an l-Thr:uridine-5'
      aldehyde transaldolase were uncovered, suggesting that C-C bond formation during
      assembly of the high carbon (C6) sugar backbone of CarU proceeds from the
      precursors UMP and l-Thr to form 5'-C-glycyluridine (C7) as a biosynthetic
      intermediate. Here, isotopic enrichment studies with the producer of A-503083s
      were used to indeed establish l-Thr as the direct source of the carboxamide of
      CarU. With this knowledge, the A-102395 gene cluster was subsequently cloned and
      characterized. A genetic system in the A-102395-producing strain was developed,
      permitting the inactivation of several genes, including those encoding the
      dioxygenase (cpr19) and transaldolase (cpr25), which abolished the production of
      A-102395, thus confirming their role in biosynthesis. Heterologous production of
      recombinant Cpr19 and CapK, the transaldolase homolog involved in A-503083
      biosynthesis, confirmed their expected function. Finally, a phosphotransferase
      (Cpr17) conferring self-resistance was functionally characterized. The results
      provide the opportunity to use comparative genomics along with in vivo and in
      vitro approaches to probe the biosynthetic mechanism of these intriguing
      structures. 

PMID- 25855793
TI  - Human DNA Exonuclease TREX1 Is Also an Exoribonuclease That Acts on Single
      stranded RNA.
AB  - 3' repair exonuclease 1 (TREX1) is a known DNA exonuclease involved in autoimmune
      disorders and the antiviral response. In this work, we show that TREX1 is also a
      RNA exonuclease. Purified TREX1 displays robust exoribonuclease activity that
      degrades single-stranded, but not double-stranded, RNA. TREX1-D200N, an Aicardi
      Goutieres syndrome disease-causing mutant, is defective in degrading RNA. TREX1
      activity is strongly inhibited by a stretch of pyrimidine residues as is a
      bacterial homolog, RNase T. Kinetic measurements indicate that the apparent Km of
      TREX1 for RNA is higher than that for DNA. Like RNase T, human TREX1 is active in
      degrading native tRNA substrates. Previously reported TREX1 crystal structures
      have revealed that the substrate binding sites are open enough to accommodate the
      extra hydroxyl group in RNA, further supporting our conclusion that TREX1 acts on
      RNA. These findings indicate that its RNase activity needs to be taken into
      account when evaluating the physiological role of TREX1. 

PMID- 25855792
TI  - Signaling, Regulation, and Specificity of the Type II p21-activated Kinases.
AB  - The p21-activated kinases (PAKs) are a family of six serine/threonine kinases
      that act as key effectors of RHO family GTPases in mammalian cells. PAKs are
      subdivided into two groups: type I PAKs (PAK1, PAK2, and PAK3) and type II PAKs
      (PAK4, PAK5, and PAK6). Although these groups are involved in common signaling
      pathways, recent work indicates that the two groups have distinct modes of
      regulation and have both unique and common substrates. Here, we review recent
      insights into the molecular level details that govern regulation of type II PAK
      signaling. We also consider mechanisms by which signal transduction is regulated
      at the level of substrate specificity. Finally, we discuss the implications of
      these studies for clinical targeting of these kinases. 

PMID- 25855795
TI  - Diagnosis and treatment of pericarditis.

PMID- 25855794
TI  - Hyaluronidase Hyal1 Increases Tumor Cell Proliferation and Motility through
      Accelerated Vesicle Trafficking.
AB  - Hyaluronan (HA) turnover accelerates metastatic progression of prostate cancer in
      part by increasing rates of tumor cell proliferation and motility. To determine
      the mechanism, we overexpressed hyaluronidase 1 (Hyal1) as a fluorescent fusion
      protein and examined its impact on endocytosis and vesicular trafficking.
      Overexpression of Hyal1 led to increased rates of internalization of HA and the
      endocytic recycling marker transferrin. Live imaging of Hyal1, sucrose gradient
      centrifugation, and specific colocalization of Rab GTPases defined the
      subcellular distribution of Hyal1 as early and late endosomes, lysosomes, and
      recycling vesicles. Manipulation of vesicular trafficking by chemical inhibitors
      or with constitutively active and dominant negative Rab expression constructs
      caused atypical localization of Hyal1. Using the catalytically inactive point
      mutant Hyal1-E131Q, we found that enzymatic activity of Hyal1 was necessary for
      normal localization within the cell as Hyal1-E131Q was mainly detected within the
      endoplasmic reticulum. Expression of a HA-binding point mutant, Hyal1-Y202F,
      revealed that secretion of Hyal1 and concurrent reuptake from the extracellular
      space are critical for rapid HA internalization and cell proliferation. Overall,
      excess Hyal1 secretion accelerates endocytic vesicle trafficking in a substrate
      dependent manner, promoting aggressive tumor cell behavior. 

PMID- 25855796
TI  - Higher circulating adiponectin levels are associated with increased risk of
      atrial fibrillation in older adults.
AB  - BACKGROUND: Adiponectin has cardioprotective properties, suggesting that lower
      levels seen in obesity and diabetes could heighten risk of atrial fibrillation
      (AF). Among older adults, however, higher adiponectin has been linked to greater
      incidence of adverse outcomes associated with AF, although recent reports have
      shown this association to be U-shaped. We postulated that higher adiponectin
      would be linked to increased risk for AF in older adults in a U-shaped manner.
      METHODS: We examined the associations of total and high-molecular-weight (HMW)
      adiponectin with incident AF among individuals free of prevalent cardiovascular
      disease (CVD) participating in a population-based cohort study of older adults
      (n=3190; age=74+/-5 years). RESULTS: During median follow-up of 11.4 years, there
      were 886 incident AF events. Adjusted cubic splines showed a positive and linear
      association between adiponectin and incident AF. After adjusting for potential
      confounders, including amino-terminal pro-B-type natriuretic peptide 1-76, the HR
      (95% CI) for AF per SD increase in total adiponectin was 1.14 (1.05 to 1.24),
      while that for HMW adiponectin was 1.17 (1.08 to 1.27). Additional adjustment for
      putative mediators, including subclinical CVD, diabetes, lipids and inflammation,
      did not significantly affect these estimates. CONCLUSIONS: The present findings
      demonstrate that higher, not lower, levels of adiponectin are independently
      associated with increased risk of AF in older adults despite its documented
      cardiometabolic benefits. Additional work is necessary to determine if
      adiponectin is a marker of failed counter-regulatory pathways or whether this
      hormone is directly harmful in the setting of or as a result of advanced age.

PMID- 25855797
TI  - Culprit or multivessel revascularisation in ST-elevation myocardial infarction
      with cardiogenic shock.
AB  - OBJECTIVE: The value of multivessel revascularisation in cardiogenic shock and
      multivessel disease (MVD) is still not clear. We compared outcomes following
      culprit vessel or multivessel revascularisation in patients with ST-elevation
      myocardial infarction (STEMI), cardiogenic shock and MVD. METHODS: From 16 620
      patients with STEMI who underwent primary percutaneous coronary intervention
      (PCI) in a nationwide, prospective, multicentre registry between January 2006 and
      December 2012, 510 eligible patients were selected and divided into culprit
      vessel revascularisation (n=386, 75.7%) and multivessel revascularisation (n=124,
      24.3%) groups. The primary outcomes were inhospital mortality and all-cause death
      during a median 194-day follow-up. A weighted Cox regression model was
      constructed to determine the HRs and 95% CIs for outcomes in the two groups.
      RESULTS: Compared with culprit vessel revascularisation, multivessel
      revascularisation had a significantly lower adjusted risk of inhospital mortality
      (9.3% vs 2.4%, HR 0.263, 95% CI 0.149 to 0.462, p<0.001) and all-cause death
      (13.1% vs 4.8%, HR 0.400, 95% CI 0.264 to 0.606, p<0.001), mainly because of
      fewer cardiac deaths (9.7% vs 4.8%, HR 0.510, 95% CI 0.329 to 0.790, p=0.002). In
      addition, multivessel revascularisation significantly decreased the adjusted risk
      of the composite endpoint of all-cause death, recurrent myocardial infarction and
      any revascularisation (20.3% vs 18.1%, HR 0.728, 95% CI 0.55 to 0.965, p=0.026).
      CONCLUSIONS: This study showed that, compared with culprit vessel
      revascularisation, multivessel revascularisation at the time of primary PCI was
      associated with better outcomes in patients with STEMI with cardiogenic shock.
      Our results support the current guidelines regarding revascularisation in these
      patients.

PMID- 25855798
TI  - Twenty-five-year trends in myocardial infarction attack and mortality rates, and
      case-fatality, in six European populations.
AB  - OBJECTIVE: Due to the burden of coronary heart disease (CHD), the monitoring of
      CHD trends is required. This study sought to examine the acute myocardial
      infarction (AMI) trends in attack and mortality rates, and in 28-day case
      fatality, in six European populations during 1985-2010. METHODS: Data consisted
      of 78 128 AMI events included in eight population-based registries from Finland
      (several populations), Italy (Brianza and Varese), Germany (Augsburg), France
      (Haute-Garonne), Spain (Girona) and Estonia (Tallinn). AMI event rates and case
      fatality trends were analysed using the annual percentage change (APC) obtained
      by negative binomial and joinpoint regression. RESULTS: AMI attack and mortality
      rates decreased in most populations. Finland experienced the steepest decline in
      attack rates (APC=-4.4% (95% CI -5.1 to -2.9) in men; -4.0% (-5.1 to -2.8), in
      women). Total-hospital and inhospital case-fatality decreased in all populations
      except in Tallinn. The steepest decline in total case-fatality occurred in Spain
      (-3.8% (-5.3 to -2.4) in men; -5.1% (-6.9 to -3.3) in women). Prehospital case
      fatality trends differed significantly by population and sex. The trends for all
      included populations showed a significant decline in AMI event rates and case
      fatality, in both sexes and all age groups. However, in women aged 65-74 years, a
      significant increase in total case-fatality occurred in 2005-2010 (4.7% (0.7 to
      8.8)). CONCLUSIONS: AMI event rates and inhospital case-fatality declined in 1985
      2010 in almost all populations analysed. Prehospital case-fatality declined only
      in certain population groups, showing differences by sex. These results highlight
      the need of specific strategies in AMI prevention for certain groups and
      populations.

PMID- 25855799
TI  - The role of biological markers of epithelial to mesenchymal transition in
      oesophageal adenocarcinoma, an immunohistochemical study.
AB  - BACKGROUND: E-cadherin, beta-catenin, epidermal growth factor receptor (EGFR),
      neuronal cadherin (N-cadherin) and Cyclin D1 are involved in epithelial to
      mesenchymal transition (EMT). However, the prognostic significance of EMT markers
      in oesophageal adenocarcinoma (OAC) is unknown. Aim of this study was to evaluate
      the prognostic value of, and the association between different EMT markers in
      OAC. METHODS: Tumour cores of 154 patients with OAC were included in a tissue
      microarray. Scoring criteria was based on immunohistochemical staining intensity.
      RESULTS: EMT-associated markers were expressed in OAC: reduced membranous E
      cadherin and beta-catenin were seen in 11.4% and 51.7%, nuclear beta-catenin in
      19.1% and EGFR and Cyclin D1 overexpression in 56.5% and 27.4% of tumours.
      Mesenchymal marker N-cadherin was not expressed in OAC. A positive correlation
      was seen between membranous beta-catenin and E-cadherin expression (R=0.209,
      p=0.001) and between EGFR and Cyclin D1 (R=0.257, p=0.002). In univariate
      analysis, EGFR overexpression and membranous beta-catenin staining were
      significantly associated with a poor survival (HR 2.145; 95% CI 1.429 to 3.218,
      p<0.001 and HR 1.665; 95% CI 1.114 to 2.488; p=0.013). However, Cyclin D1 (HR
      1.092; 95% CI 0.702 to 1.698; p=0.697), nuclear beta-catenin (HR 1.322; 95% CI
      0.799 to 2.189; p=0.277) and E-cadherin (HR 1.012; 95% CI 0.554 to 1.851;
      p=0.968) were not associated with survival. In multivariate analysis, EGFR
      overexpression was an independent prognostic factor for poor survival (HR 1.678;
      95% CI 1.055 to 2.668; p=0.029) together with T stage (HR 2.759; 95% CI 1.356 to
      5.576; p=0.005). CONCLUSIONS: This study supports the presence of EMT in OAC.
      Moreover, EGFR overexpression was independently associated with a poor survival.

PMID- 25855800
TI  - Infrequent DNA methylation of miR-9-1 and miR-9-3 in multiple myeloma.
AB  - AIMS: The miR-9 family microRNAs (miRNAs) are tumour suppressor miRNAs implicated
      in carcinogenesis. We postulated that miR-9-1, miR-9-2 and miR-9-3 may be
      inactivated by aberrant promoter methylation in multiple myeloma (MM). METHODS:
      Methylation of miR-9-1, miR-9-2 and miR-9-3 was studied by methylation-specific
      PCR (MSP) in six normal controls, including three each of healthy peripheral
      blood (PB) or bone marrow buffy coat, 10 MM cell lines, 62 primary MM marrow
      samples at diagnosis and 22 at relapse/progression. RESULTS: MSP, verified by
      quantitative pyrosequencing, showed that the promoters of miR-9-3 and miR-9-1
      were unmethylated in normal controls but methylated in 4 (40%) and 5 (50%) of 10
      MM cell lines, respectively. However, the promoter of miR-9-2 was methylated in
      three normal PB buffy coat controls and in CD138-sorted healthy marrow plasma
      cells, indicating possibly tissue specific rather than tumour-specific
      methylation of miR-9-2, which was thus not studied further. In WL-2 cells, which
      were completely methylated for miR-9-3, 5-aza-2'-deoxycytidine treatment caused
      miR-9-3 promoter demethylation and pri-miR-9-3 re-expression. In primary samples,
      methylation of miR-9-3 was detected in 1 of 62 patients at diagnosis and 1 of 22
      patients at relapse/progression. However, miR-9-1 methylation was absent in both
      primary samples at diagnosis and at relapse/progression. CONCLUSIONS:
      Hypermethylation of miR-9-3 and miR-9-1 is tumour-specific in MM, leading to
      reversible miRNA silencing. Frequent methylation of miR-9-3 and miR-9-1 in cell
      lines, but not in primary samples, may be acquired during in vitro culture, and
      indicates an unimportant role of miR-9 methylation in myelomagenesis.

PMID- 25855801
TI  - False negative rate for intraoperative sentinel lymph node frozen section in
      patients with breast cancer: a retrospective analysis of patients in a single
      Asian institution.
AB  - BACKGROUND AND OBJECTIVE: Intraoperative frozen section of the sentinel lymph
      node (SLN) in clinically node negative breast cancer patients detects metastatic
      disease and enables axillary lymph node dissection to be performed in the same
      operative setting. Internationally, the false negative rate (FNR) for SLN biopsy
      ranges from 5.5% to 43%. The size of SLN metastasis has been identified as a key
      factor affecting FNR. We review our institutional experience on the accuracy of
      intraoperative SLN biopsy. METHODS: Data were collected retrospectively from
      patients undergoing SLN biopsy performed at Singapore General Hospital. The SLN
      was identified using blue dye, radioisotope or both. Frozen section was performed
      intraoperatively. When SLN was positive for metastasis on frozen section,
      completion axillary clearance was performed. False negative cases were defined as
      patients in whom a negative frozen section result was obtained, whose final
      permanent paraffin section was positive. We determined the FNR of SLN frozen
      section and evaluated the factors associated with it. RESULTS: A total of 2202
      SLN biopsies were performed between January 2005 and June 2012. There were 89
      false negative cases, of which there were 23 (25.8%) cases of isolated tumour
      cells (ITCs), 49 (55.1%) cases of micrometastasis, and 17 (19.1%) cases of
      macrometastasis. The overall FNR was 13.5%. FNR was 79.3% in ITCs, 59.8% in
      micrometastasis, and 3.1% in macrometastatic disease. Non-ductal histological
      subtype, absence of lymphovascular invasion and the size of SLN metastasis were
      identified as significant independent factors associated with a higher FNR.
      CONCLUSIONS: FNRin our institution is acceptable when compared to other large
      centres. Failure to detect metastasis in frozen section in more than half of our
      patients was due to ITCs and micrometastasis.

PMID- 25855802
TI  - Vitreal delivery of AAV vectored Cnga3 restores cone function in CNGA3-/-/Nrl-/-
      mice, an all-cone model of CNGA3 achromatopsia.
AB  - The CNGA3(-/-)/Nrl(-/-) mouse is a cone-dominant model with Cnga3 channel
      deficiency, which partially mimics the all cone foveal structure of human
      achromatopsia 2 with CNGA3 mutations. Although subretinal (SR) AAV vector
      administration can transfect retinal cells efficiently, the injection-induced
      retinal detachment can cause retinal damage, particularly when SR vector bleb
      includes the fovea. We therefore explored whether cone function-structure could
      be rescued in CNGA3(-/-)/Nrl(-/-) mice by intravitreal (IVit) delivery of
      tyrosine to phenylalanine (Y-F) capsid mutant AAV8. We find that AAV-mediated
      CNGA3 expression can restore cone function and rescue structure following IVit
      delivery of AAV8 (Y447, 733F) vector. Rescue was assessed by restoration of the
      cone-mediated electroretinogram (ERG), optomotor responses, and cone opsin
      immunohistochemistry. Demonstration of gene therapy in a cone-dominant mouse
      model by IVit delivery provides a potential alternative vector delivery mode for
      safely transducing foveal cones in achromatopsia patients and in other human
      retinal diseases affecting foveal function. 

PMID- 25855803
TI  - Germline recessive mutations in PI4KA are associated with perisylvian
      polymicrogyria, cerebellar hypoplasia and arthrogryposis.
AB  - Polymicrogyria (PMG) is a structural brain abnormality involving the cerebral
      cortex that results from impaired neuronal migration and although several genes
      have been implicated, many cases remain unsolved. In this study, exome sequencing
      in a family where three fetuses had all been diagnosed with PMG and cerebellar
      hypoplasia allowed us to identify regions of the genome for which both
      chromosomes were shared identical-by-descent, reducing the search space for
      causative variants to 8.6% of the genome. In these regions, the only plausibly
      pathogenic mutations were compound heterozygous variants in PI4KA, which Sanger
      sequencing confirmed segregated consistent with autosomal recessive inheritance.
      The paternally transmitted variant predicted a premature stop mutation
      (c.2386C>T; p.R796X), whereas the maternally transmitted variant predicted a
      missense substitution (c.5560G>A; p.D1854N) at a conserved residue within the
      catalytic domain. Functional studies using expressed wild-type or mutant PI4KA
      enzyme confirmed the importance of p.D1854 for kinase activity. Our results
      emphasize the importance of phosphoinositide signalling in early brain
      development. 

PMID- 25855804
TI  - Adoptive Transfer of MAGE-A4 T-cell Receptor Gene-Transduced Lymphocytes in
      Patients with Recurrent Esophageal Cancer.
AB  - PURPOSE: Preparative lymphodepletion, the temporal ablation of the immune system,
      has been reported to promote persistence of transferred cells along with
      increased rates of tumor regression in patients treated with adoptive T-cell
      therapy. However, it remains unclear whether lymphodepletion is indispensable for
      immunotherapy with T-cell receptor (TCR) gene-engineered T cells. EXPERIMENTAL
      DESIGN: We conducted a first-in-man clinical trial of TCR gene-transduced T-cell
      transfer in patients with recurrent MAGE-A4-expressing esophageal cancer. The
      patients were given sequential MAGE-A4 peptide vaccinations. The regimen included
      neither lymphocyte-depleting conditioning nor administration of IL2. Ten
      patients, divided into 3 dose cohorts, received T-cell transfer. RESULTS: TCR
      transduced cells were detected in the peripheral blood for 1 month at levels
      proportional to the dose administered, and in 5 patients they persisted for more
      than 5 months. The persisting cells maintained ex vivo antigen-specific tumor
      reactivity. Despite the long persistence of the transferred T cells, 7 patients
      exhibited tumor progression within 2 months after the treatment. Three patients
      who had minimal tumor lesions at baseline survived for more than 27 months.
      CONCLUSIONS: These results suggest that TCR-engineered T cells created by
      relatively short-duration in vitro culture of polyclonal lymphocytes in
      peripheral blood retained the capacity to survive in a host. The discordance
      between T-cell survival and tumor regression suggests that multiple mechanisms
      underlie the benefits of preparative lymphodepletion in adoptive T-cell therapy.

PMID- 25855806
TI  - TCS: a web server for multiple sequence alignment evaluation and phylogenetic
      reconstruction.
AB  - This article introduces the Transitive Consistency Score (TCS) web server; a
      service making it possible to estimate the local reliability of protein multiple
      sequence alignments (MSAs) using the TCS index. The evaluation can be used to
      identify the aligned positions most likely to contain structurally analogous
      residues and also most likely to support an accurate phylogenetic reconstruction.
      The TCS scoring scheme has been shown to be accurate predictor of structural
      alignment correctness among commonly used methods. It has also been shown to
      outperform common filtering schemes like Gblocks or trimAl when doing MSA post
      processing prior to phylogenetic tree reconstruction. The web server is available
      from http://tcoffee.crg.cat/tcs. 

PMID- 25855805
TI  - Unique C. elegans telomeric overhang structures reveal the evolutionarily
      conserved properties of telomeric DNA.
AB  - There are two basic mechanisms that are associated with the maintenance of the
      telomere length, which endows cancer cells with unlimited proliferative
      potential. One mechanism, referred to as alternative lengthening of telomeres
      (ALT), accounts for approximately 10-15% of all human cancers. Tumours engaged in
      the ALT pathway are characterised by the presence of the single stranded 5'-C
      rich telomeric overhang (C-overhang). This recently identified hallmark of ALT
      cancers distinguishes them from healthy tissues and renders the C-overhang as a
      clear target for anticancer therapy. We analysed structures of the 5'-C-rich and
      3'-G-rich telomeric overhangs from human and Caenorhabditis elegans, the recently
      established multicellular in vivo model of ALT tumours. We show that the
      telomeric DNA from C. elegans and humans forms fundamentally different secondary
      structures. The unique structural characteristics of C. elegans telomeric DNA
      that are distinct not only from those of humans but also from those of other
      multicellular eukaryotes allowed us to identify evolutionarily conserved
      properties of telomeric DNA. Differences in structural organisation of the
      telomeric DNA between the C. elegans and human impose limitations on the use of
      the C. elegans as an ALT tumour model. 

PMID- 25855807
TI  - The EBI Search engine: providing search and retrieval functionality for
      biological data from EMBL-EBI.
AB  - The European Bioinformatics Institute (EMBL-EBI-https://www.ebi.ac.uk) provides
      free and unrestricted access to data across all major areas of biology and
      biomedicine. Searching and extracting knowledge across these domains requires a
      fast and scalable solution that addresses the requirements of domain experts as
      well as casual users. We present the EBI Search engine, referred to here as 'EBI
      Search', an easy-to-use fast text search and indexing system with powerful data
      navigation and retrieval capabilities. API integration provides access to
      analytical tools, allowing users to further investigate the results of their
      search. The interconnectivity that exists between data resources at EMBL-EBI
      provides easy, quick and precise navigation and a better understanding of the
      relationship between different data types including sequences, genes, gene
      products, proteins, protein domains, protein families, enzymes and macromolecular
      structures, together with relevant life science literature. 

PMID- 25855808
TI  - Determinants of the CmoB carboxymethyl transferase utilized for selective tRNA
      wobble modification.
AB  - Enzyme-mediated modifications at the wobble position of tRNAs are essential for
      the translation of the genetic code. We report the genetic, biochemical and
      structural characterization of CmoB, the enzyme that recognizes the unique
      metabolite carboxy-S-adenosine-L-methionine (Cx-SAM) and catalyzes a
      carboxymethyl transfer reaction resulting in formation of 5-oxyacetyluridine at
      the wobble position of tRNAs. CmoB is distinctive in that it is the only known
      member of the SAM-dependent methyltransferase (SDMT) superfamily that utilizes a
      naturally occurring SAM analog as the alkyl donor to fulfill a biologically
      meaningful function. Biochemical and genetic studies define the in vitro and in
      vivo selectivity for Cx-SAM as alkyl donor over the vastly more abundant SAM.
      Complementary high-resolution structures of the apo- and Cx-SAM bound CmoB reveal
      the determinants responsible for this remarkable discrimination. Together, these
      studies provide mechanistic insight into the enzymatic and non-enzymatic feature
      of this alkyl transfer reaction which affords the broadened specificity required
      for tRNAs to recognize multiple synonymous codons. 

PMID- 25855809
TI  - 2'-Fluoro-modified phosphorothioate oligonucleotide can cause rapid degradation
      of P54nrb and PSF.
AB  - Synthetic oligonucleotides are used to regulate gene expression through different
      mechanisms. Chemical modifications of the backbone of the nucleic acid and/or of
      the 2' moiety of the ribose can increase nuclease stability and/or binding
      affinity of oligonucleotides to target molecules. Here we report that
      transfection of 2'-F-modified phosphorothioate oligonucleotides into cells can
      reduce the levels of P54nrb and PSF proteins through proteasome-mediated
      degradation. Such deleterious effects of 2'-F-modified oligonucleotides were
      observed in different cell types from different species, and were independent of
      oligonucleotide sequence, positions of the 2'-F-modified nucleotides in the
      oligonucleotides, method of delivery or mechanism of action of the
      oligonucleotides. Four 2'-F-modified nucleotides were sufficient to cause the
      protein reduction. P54nrb and PSF belong to Drosophila behavior/human splicing
      (DBHS) family. The third member of the family, PSPC1, was also reduced by the 2'
      F-modified oligonucleotides. Preferential association of 2'-F-modified
      oligonucleotides with P54nrb was observed, which is partially responsible for the
      protein reduction. Consistent with the role of DBHS proteins in double-strand DNA
      break (DSB) repair, elevated DSBs were observed in cells treated with 2'-F
      modified oligonucleotides, which contributed to severe impairment in cell
      proliferation. These results suggest that oligonucleotides with 2'-F
      modifications can cause non-specific loss of cellular protein(s). 

PMID- 25855811
TI  - SANSparallel: interactive homology search against Uniprot.
AB  - Proteins evolve by mutations and natural selection. The network of sequence
      similarities is a rich source for mining homologous relationships that inform on
      protein structure and function. There are many servers available to browse the
      network of homology relationships but one has to wait up to a minute for results.
      The SANSparallel webserver provides protein sequence database searches with
      immediate response and professional alignment visualization by third-party
      software. The output is a list, pairwise alignment or stacked alignment of
      sequence-similar proteins from Uniprot, UniRef90/50, Swissprot or Protein Data
      Bank. The stacked alignments are viewed in Jalview or as sequence logos. The
      database search uses the suffix array neighborhood search (SANS) method, which
      has been re-implemented as a client-server, improved and parallelized. The method
      is extremely fast and as sensitive as BLAST above 50% sequence identity.
      Benchmarks show that the method is highly competitive compared to previously
      published fast database search programs: UBLAST, DIAMOND, LAST, LAMBDA,
      RAPSEARCH2 and BLAT. The web server can be accessed interactively or
      programmatically at http://ekhidna2.biocenter.helsinki.fi/cgi-bin/sans/sans.cgi.
      It can be used to make protein functional annotation pipelines more efficient,
      and it is useful in interactive exploration of the detailed evidence supporting
      the annotation of particular proteins of interest. 

PMID- 25855810
TI  - The COP9 signalosome is vital for timely repair of DNA double-strand breaks.
AB  - The DNA damage response is vigorously activated by DNA double-strand breaks
      (DSBs). The chief mobilizer of the DSB response is the ATM protein kinase. We
      discovered that the COP9 signalosome (CSN) is a crucial player in the DSB
      response and an ATM target. CSN is a protein complex that regulates the activity
      of cullin ring ubiquitin ligase (CRL) complexes by removing the ubiquitin-like
      protein, NEDD8, from their cullin scaffold. We find that the CSN is physically
      recruited to DSB sites in a neddylation-dependent manner, and is required for
      timely repair of DSBs, affecting the balance between the two major DSB repair
      pathways-nonhomologous end-joining and homologous recombination repair (HRR). The
      CSN is essential for the processivity of deep end-resection-the initial step in
      HRR. Cullin 4a (CUL4A) is recruited to DSB sites in a CSN- and neddylation
      dependent manner, suggesting that CSN partners with CRL4 in this pathway.
      Furthermore, we found that ATM-mediated phosphorylation of CSN subunit 3 on S410
      is critical for proper DSB repair, and that loss of this phosphorylation site
      alone is sufficient to cause a DDR deficiency phenotype in the mouse. This novel
      branch of the DSB response thus significantly affects genome stability. 

PMID- 25855812
TI  - MTiOpenScreen: a web server for structure-based virtual screening.
AB  - Open screening endeavors play and will play a key role to facilitate the
      identification of new bioactive compounds in order to foster innovation and to
      improve the effectiveness of chemical biology and drug discovery processes. In
      this line, we developed the new web server MTiOpenScreen dedicated to small
      molecule docking and virtual screening. It includes two services, MTiAutoDock and
      MTiOpenScreen, allowing performing docking into a user-defined binding site or
      blind docking using AutoDock 4.2 and automated virtual screening with AutoDock
      Vina. MTiOpenScreen provides valuable starting collections for screening, two in
      house prepared drug-like chemical libraries containing 150 000 PubChem compounds:
      the Diverse-lib containing diverse molecules and the iPPI-lib enriched in
      molecules likely to inhibit protein-protein interactions. In addition,
      MTiOpenScreen offers users the possibility to screen up to 5000 small molecules
      selected outside our two libraries. The predicted binding poses and energies of
      up to 1000 top ranked ligands can be downloaded. In this way, MTiOpenScreen
      enables researchers to apply virtual screening using different chemical libraries
      on traditional or more challenging protein targets such as protein-protein
      interactions. The MTiOpenScreen web server is free and open to all users at
      http://bioserv.rpbs.univ-paris-diderot.fr/services/MTiOpenScreen/. 

PMID- 25855813
TI  - WAXSiS: a web server for the calculation of SAXS/WAXS curves based on explicit
      solvent molecular dynamics.
AB  - Small- and wide-angle X-ray scattering (SWAXS) has evolved into a powerful tool
      to study biological macromolecules in solution. The interpretation of SWAXS
      curves requires their accurate predictions from structural models. Such
      predictions are complicated by scattering contributions from the hydration layer
      and by effects from thermal fluctuations. Here, we describe the new web server
      WAXSiS (WAXS in solvent) that computes SWAXS curves based on explicit-solvent all
      atom molecular dynamics (MD) simulations (http://waxsis.uni-goettingen.de/). The
      MD simulations provide a realistic model for both the hydration layer and the
      excluded solvent, thereby avoiding any solvent-related fitting parameters, while
      naturally accounting for thermal fluctuations. 

PMID- 25855814
TI  - Structural and functional analysis of the Rpf2-Rrs1 complex in ribosome
      biogenesis.
AB  - Proteins Rpf2 and Rrs1 are required for 60S ribosomal subunit maturation. These
      proteins are necessary for the recruitment of three ribosomal components (5S
      ribosomal RNA [rRNA], RpL5 and RpL11) to the 90S ribosome precursor and
      subsequent 27SB pre-rRNA processing. Here we present the crystal structure of the
      Aspergillus nidulans (An) Rpf2-Rrs1 core complex. The core complex contains the
      tightly interlocked N-terminal domains of Rpf2 and Rrs1. The Rpf2 N-terminal
      domain includes a Brix domain characterized by similar N- and C-terminal
      architecture. The long alpha-helix of Rrs1 joins the C-terminal half of the Brix
      domain as if it were part of a single molecule. The conserved proline-rich linker
      connecting the N- and C-terminal domains of Rrs1 wrap around the side of Rpf2 and
      anchor the C-terminal domain of Rrs1 to a specific site on Rpf2. In addition, gel
      shift analysis revealed that the Rpf2-Rrs1 complex binds directly to 5S rRNA.
      Further analysis of Rpf2-Rrs1 mutants demonstrated that Saccharomyces cerevisiae
      Rpf2 R236 (corresponds to R238 of AnRpf2) plays a significant role in this
      binding. Based on these studies and previous reports, we have proposed a model
      for ribosomal component recruitment to the 90S ribosome precursor. 

PMID- 25855815
TI  - Are mutagenic non D-loop direct repeat motifs in mitochondrial DNA under a
      negative selection pressure?
AB  - Non D-loop direct repeats (DRs) in mitochondrial DNA (mtDNA) have been commonly
      implicated in the mutagenesis of mtDNA deletions associated with neuromuscular
      disease and ageing. Further, these DRs have been hypothesized to put a constraint
      on the lifespan of mammals and are under a negative selection pressure. Using a
      compendium of 294 mammalian mtDNA, we re-examined the relationship between
      species lifespan and the mutagenicity of such DRs. Contradicting the prevailing
      hypotheses, we found no significant evidence that long-lived mammals possess
      fewer mutagenic DRs than short-lived mammals. By comparing DR counts in human
      mtDNA with those in selectively randomized sequences, we also showed that the
      number of DRs in human mtDNA is primarily determined by global mtDNA properties,
      such as the bias in synonymous codon usage (SCU) and nucleotide composition. We
      found that SCU bias in mtDNA positively correlates with DR counts, where repeated
      usage of a subset of codons leads to more frequent DR occurrences. While bias in
      SCU and nucleotide composition has been attributed to nucleotide mutational bias,
      mammalian mtDNA still exhibit higher SCU bias and DR counts than expected from
      such mutational bias, suggesting a lack of negative selection against non D-loop
      DRs. 

PMID- 25855816
TI  - The HIV-1 Rev response element (RRE) adopts alternative conformations that
      promote different rates of virus replication.
AB  - The HIV Rev protein forms a complex with a 351 nucleotide sequence present in
      unspliced and incompletely spliced human immunodeficiency virus (HIV) mRNAs, the
      Rev response element (RRE), to recruit the cellular nuclear export receptor Crm1
      and Ran-GTP. This complex facilitates nucleo-cytoplasmic export of these mRNAs.
      The precise secondary structure of the HIV-1 RRE has been controversial, since
      studies have reported alternative structures comprising either four or five stem
      loops. The published structures differ only in regions that lie outside of the
      primary Rev binding site. Using in-gel SHAPE, we have now determined that the wt
      NL4-3 RRE exists as a mixture of both structures. To assess functional
      differences between these RRE 'conformers', we created conformationally locked
      mutants by site-directed mutagenesis. Using subgenomic reporters, as well as HIV
      replication assays, we demonstrate that the five stem-loop form of the RRE
      promotes greater functional Rev/RRE activity compared to the four stem-loop
      counterpart. 

PMID- 25855818
TI  - Erratum: Mohty M, Malard F, Blaise D, Milpied N, Furst S, Tabrizi R, Guillaume T,
      Vigouroux S, El-Cheikh J, Delaunay J, Le Gouill S, Moreau P, Labopin M and
      Chevallier P. Reduced-toxicity conditioning with fludarabine, once-daily
      intravenous busulfan, and antithymocyte globulins prior to allogeneic stem cell
      transplantation: Results of a multicenter prospective phase 2 trial. Cancer. doi:
      10.1002/cncr.29087.
AB  - In Table 1, the numbers for NHL should be 20(25%). In the legend for Figure 1,
      part (B) should read chronic GVHD is shown. The authors regret these errors.

PMID- 25855817
TI  - Polymerization stress of dental resin composite continues to develop 12 hours
      after irradiation.
AB  - OBJECTIVE: This study assessed the development of stress from polymerization of
      light-cured dental resin composites for 24 hours after irradiation. MATERIALS AND
      METHODS: Initial cracks were made near the edge of a cylindrical hole in glass,
      and crack lengths were measured. Revolution Formula 2, Kalore and Venus Diamond
      were polymerized in the hole. Crack lengths were measured at several intervals
      after irradiation up to 24 hours. Stresses at the composite-glass interface were
      calculated using the crack lengths. Elastic moduli of the composites were
      measured at the same time intervals. RESULTS: Interfacial stress and elastic
      modulus were significantly related to material and time. Stress continued to
      increase up to 12 hours after irradiation. Significantly lower stresses were
      measured in Kalore and Venus Diamond than Revolution Formula 2 throughout 24
      hours. Stress at 24 hours was two times greater than the stress at 30 minutes.
      The increase in elastic modulus from 30 minutes to 24 hours ranged from 8 to 24%,
      which was less than the increase in stress over the same time period.
      CONCLUSIONS: Interfacial stress and elastic modulus of the composites
      demonstrated the average increases of 155% and 14%, respectively, from 30 minutes
      to 24 hours after irradiation. CLINICAL SIGNIFICANCE: Since the elastic modulus
      is a measure of stiffness and resistance to load, clinicians might consider
      advising their patients to avoid heavy occlusal function until the elastic
      modulus has reached a plateau, which would be 60 minutes for Venus Diamond, 12
      hours for Kalore, and 24 hours for Revolution Formula 2.

PMID- 25855819
TI  - Erratum: Boyle EM, Fouquet G, Guidez S, Bonnet S, Demarquette H, Dulery R,
      Herbaux C, Noel MP, Manier S, Schraen S, Onraed B, Faucompre J-L, Hennache B,
      Petillon MO, Mathiot C, Avet-Loiseau H, Facon T, Harding SJ, Moreau P and Leleu
      X. IgA kappa/IgA lambda heavy/light chain assessment in the management of
      patients with IgA myeloma. Cancer. doi: 10.1002/cncr.28946.
AB  - Please note that Table 1 and Table 2 were mistakenly inverted. The authors regret
      this error.

PMID- 25855820
TI  - Erratum: Borderud SP, Li Y, Burkhalter JE, Sheffer CE and Ostroff JS.  Electronic
      cigarette use among patients with cancer: Characteristics of electronic 
      cigarette users and their smoking cessation outcomes. Cancer. doi: 10.1002/ 
      cncr.28811.
AB  - The authors discovered some errors regarding reference group labels in Table 2.
      The corrected table is attached. The authors regret these errors.

PMID- 25855821
TI  - Paediatric pharmacokinetics: key considerations.
AB  - A number of anatomical and physiological factors determine the pharmacokinetic
      profile of a drug. Differences in physiology in paediatric populations compared
      with adults can influence the concentration of drug within the plasma or tissue.
      Healthcare professionals need to be aware of anatomical and physiological changes
      that affect pharmacokinetic profiles of drugs to understand consequences of dose
      adjustments in infants and children. Pharmacokinetic clinical trials in children
      are complicated owing to the limitations on blood sample volumes and perception
      of pain in children resulting from blood sampling. There are alternative sampling
      techniques that can minimize the invasive nature of such trials. Population based
      models can also limit the sampling required from each individual by increasing
      the overall sample size to generate robust pharmacokinetic data. This review
      details key considerations in the design and development of paediatric
      pharmacokinetic clinical trials.

PMID- 25855822
TI  - Formulations for children: problems and solutions.
AB  - Paediatric formulation design is complex as there is a need to understand the
      developmental physiological changes that occur during childhood and their impact
      on the absorption of drugs. Paediatric dose adjustments are usually based on
      achieving pharmacokinetic or pharmacodynamic profiles equivalent to those
      achieved in adult populations. However, differences in the way in which children
      handle adult products or the use of bespoke paediatric formulations can result in
      unexpected pharmacokinetic drug profiles with altered clinical efficacy.
      Differences in drug formulations need to be understood by healthcare
      professionals involved in the prescribing, administration or dispensing of drugs
      to children such that appropriate advice is given to ensure that therapeutic
      outcomes are achieved. This issue is not confined to oral medicines but is
      applicable for all routes of administration encountered in paediatric therapy.

PMID- 25855824
TI  - Should hormone therapy be recommended for prevention of cardiovascular disease?

PMID- 25855823
TI  - Pharmacogenomics--how close/far are we to practising individualized medicine for
      children?
AB  - The translation of pharmacogenomics into clinical practice is a key approach for
      practising individualized medicine, which aims to maximize drug efficacy and
      minimize drug toxicity. Since the completion of both the Human Genome Project and
      the International HapMap project, the development of pharmacogenomics has been
      greatly facilitated. However, progress in translating pharmacogenomics into
      clinical practice, especially in paediatric medicine, is unexpectedly slow. Many
      challenges from different areas remain. This paper discusses the existing
      applications and the limitations to the implementation of paediatric
      pharmacogenomics, as well as possible solutions for overcoming these limitations
      and challenges.

PMID- 25855825
TI  - [Maker, inventor, doctor].

PMID- 25855826
TI  - [The call for "ancient medicine from the test tube"].

PMID- 25855827
TI  - [65-year-old man after resuscitation].

PMID- 25855828
TI  - Exhibition, Breaking through the binary.

PMID- 25855829
TI  - Female odours promote the activation of sheltered kissing bug Rhodnius prolixus
      males and modulate their orientation.
AB  - The existence of a pheromone emitted during copulation has been reported for
      Rhodnius prolixus (Hemiptera: Reduviidae) Stal. Adults possess one pair of
      metasternal glands (MGs) from which female R. prolixus release volatiles mainly
      at night. We investigated whether these volatiles emitted by adult R. prolixus
      can modulate sexual-related behaviours of opposite and/or same sex individuals.
      We first used a shelter bioassay to test if adult activity patterns can be
      affected by chemical signals emitted by opposite sex conspecifics. We observed
      that males left the shelter more frequently in the presence of females, showing
      higher activity and an increase of intrasexual copulation attempts. Females
      showed no shelter-related activation in the presence of male odours. Second, we
      used a locomotion compensator device to investigate whether females or males show
      oriented responses to odours emitted by adults. We found that males oriented
      towards air currents carrying female odours but females did not orient towards
      odours emitted by adults. Finally, we observed that males oriented towards the
      female MG compounds. Thus, a volatile chemical signal emitted by females from
      their MGs promoted the activation of sheltered males and modulated orientation to
      air currents.

PMID- 25855830
TI  - [Convergence in Europe - a hard task?].

PMID- 25855831
TI  - [Alberto Vilar Pereira de Queiros].

PMID- 25855832
TI  - [Innovation in constrain periods!].

PMID- 25855833
TI  - Retraction. Protective role of Klotho on cardiomyocytes upon
      hypoxia/reoxygenation via downregulation of Akt and FOXO1 phosphorylation. Mol
      Med Rep 11(3): 2013-19, 2015.

PMID- 25855851
TI  - Topical platelet-derived growth factor vs placebo therapy of diabetic foot ulcers
      offloaded with windowed casts: a randomized, controlled trial.
AB  - OBJECTIVE: This study sought to compare the efficacy of topical platelet derived
      growth factor (Regranex, Smith and Nephew, London, UK) (test group) to placebo
      (control group) in treating diabetic foot ulcers. All subjects had a short leg
      walking cast with a window fashioned in the cast over the site of the ulcer.
      METHODS: Forty-six subjects were randomized (double-blind) 1:1 to the test or
      control group and treated for up to 4 months. Subjects had Wagner grade I ulcers
      with wound area of 1 cm2 to 16 cm2 without severe peripheral arterial disease,
      osteomyelitis, or any infection requiring antibiotics. Study medication was
      applied daily and casts changed approximately every 14 days. RESULTS: Of the 46
      subjects randomized, 38 either healed or completed 16 weeks of therapy without
      healing. Eight subjects dropped out prior to 16 weeks. Based on intention-to
      treat, 12 of 23 (52%) test group subjects healed before 16 weeks compared to 13
      of 23 (57%) control group subjects (not significant). Regression analysis
      demonstrated that slower healing was associated with larger initial wound size
      (hazard radio [HR] = 0.997, 95% confidence interval [CI]: 0.995-1.00, P = 0.028)
      and excessive wound drainage (HR = 0.346, 95% CI: 0.126-0.948, P = 0.039).
      Excluding the patients who dropped out, 25 of 38 (66%) subjects healed by 4
      months. Three additional subjects healed with casts that were worn longer than 4
      months, for an overall rate of 74% at 9 months. Five subjects developed cast
      burns, and 3 patients required amputation. CONCLUSION: Topical platelet derived
      growth factor does not appear to significantly improve healing of Wagner grade I
      diabetic foot ulcers that are treated by offloading with a short leg walking
      cast. Excellent healing rates may be achieved with casting alone.

PMID- 25855852
TI  - SCALE wounds: unavoidable pressure injury.
AB  - Skin Changes at Life's End (SCALE) wounds include wounds of many underlying
      etiologies that accompany the dying process. These wounds occur due to
      unmodifiable intrinsic and extrinsic factors unique to each individual. This
      article describes the case of a dying patient who sustained a skin tear that
      deteriorated into a SCALE wound that meets the criteria for a National Pressure
      Ulcer Advisory Panel unavoidable pressure injury. 

PMID- 25855853
TI  - Degree of the hazards of silver-containing dressings on MRSA-infected wounds in
      Sprague-Dawley and streptozotocin-induced diabetic rats.
AB  - Silver-containing dressings are commonly used on healing wounds, including
      diabetic ulcers. Some studies have shown that dressing materials with silver have
      negative effects on wound healing, specifically, that the wound healing process
      is inhibited by deposited silver. Therefore, the authors treated wounds infected
      with methicillin-resistant Staphylococcus aureus (MRSA) in Sprague-Dawley (SD)
      rats and streptozotocin (STZ)-induced diabetic rats with silver dressings to
      evaluate the risks of silver. MATERIALS AND METHODS: The study used 54 SD rats
      and 54 STZ-induced diabetic rats. Full-thickness skin defects were created in all
      animals and then infected with MRSA. The rats were divided into 6 groups
      according to the dressing materials: nanocrystalline silver (Ac) (ACTICOAT, Smith
      and Nephew Healthcare, Hull, UK), silver carboxymethylcellulose (Aq) (AQUACEL Ag,
      ConvaTec, Bristol-Myers Squibb, Skillman, NJ), silver sulfadiazine (M) (Medifoam
      Silver, Biopol Global Co, Ltd, Seoul, Korea), nanocrystalline silver (P) (PolyMem
      Silver, Ferris Mfg Corp, Fort Worth, TX), Ilvadon cream (I) (Ildong Pharaceutical
      Co, Ltd, Seoul, Korea), and 10% povidone iodine (B) (Betadine, Sung Kwang
      Pharmaceutical Co Ltd, Gyeonggi-Do, Korea) as a control agent. Blood was
      collected from all animals to measure the hematological effects. The skin,
      spleen, liver, and kidneys of each rat were biopsied and used to make paraffin
      sections in which the silver deposition was measured using energy-dispersive
      spectrometry (EDS). RESULTS: Fifteen days after wounding, only the Ac, P, and I
      groups differed significantly (P < 0.05) from the B group. The glutamic
      oxaloacetic transaminase, blood urea nitrogen, and alkaline phosphatase levels
      differed significantly (P < 0.05) between the SD and STZ rats. No silver
      deposition was found in any organ. CONCLUSION: The silver dressings induced
      slight liver damage in the STZ-rats. Although changes in serum chemistry caused
      by silver were seen, this did not indicate silver deposition in the organ as the
      EDS did not show excess levels. The risk of silver deposition appears to be low.
      The hazards of silver-containing dressing products in MRSA-infected wounds were
      insignificant.

PMID- 25855854
TI  - The efficacy and safety of natural honey on the healing of foot ulcers: a case
      series.
AB  - This clinical observation investigated the efficacy, cost-effectiveness, and
      acceptability of natural honey on the healing of a variety of chronic foot ulcers
      at the primary care level. MATERIALS AND METHODS: A total of 12 patients with
      foot ulcers utilizing natural honey as an effective alternative to more
      expensive, advanced wound products were followed. Cases were referred to
      Umgwailinah Primary Health Care Center, Doha, Qatar from different health centers
      and from Hamad General Hospital, Doha, Qatar. There were also self-referred
      cases. After rinsing the site with normal saline, natural honey was applied and
      the wound was covered by glycerin-impregnated gauze (Adaptic Non-Adhering
      Dressing, Systagenix, San Antonio, TX) to prevent the absorption of honey into
      the cotton gauze and away from the wound site. Patients were followed on a daily
      basis for an average of 4 weeks. RESULTS: All ulcers healed with no contractures
      or scars with a mean healing time of 3 weeks. There was a 75% reduction in the
      dressing budget of the health center and a high level of satisfaction among both
      health professionals and patients. Patients' pain levels were reduced
      significantly after using natural honey, as evidenced by the use of the Visual
      Analog Scale. CONCLUSION: The use of natural honey in the management of chronic
      foot ulcers proved to be efficacious, cost-effective, and acceptable by both
      clinicians and patients.

PMID- 25855855
TI  - Wound cleansing: how far have we come?

PMID- 25855856
TI  - Editorial message: A prescription for success.

PMID- 25855858
TI  - On the paradoxical decrease of self-reported cognitive failures with age.
AB  - The science of Human Factors and Ergonomics (HF/E) often relies on self-report.
      This is a cause for concern because subjective methods are inherently susceptible
      to bias. Here, we present, examine and discuss a puzzling association between age
      and self-reported cognitive failures as assessed with Broadbent's Cognitive
      Failures Questionnaire (CFQ). Despite many well-established age-associated forms
      of cognitive decline, older persons actually report almost equivalent, or even
      less, cognitive failures on the CFQ than younger persons. Our present analysis
      indicates that this paradox may be resolved through the fact that people show age
      related learning/adaptation/compensation and by the observation that the CFQ
      measures peoples' beliefs with respect to an individually idiosyncratic
      reference. Yet, at the heart of the paradox may be the idea that people cannot
      remember their own cognitive failures, pointing to even greater concerns with all
      forms of subjective self-report and its use in HF/E. Practitioner Summary:
      Scientists and practitioners often try to understand and improve human
      performance with the help of self-report questionnaires. Our paper discusses the
      validity of self-reported errors measured with the Cognitive Failures
      Questionnaire (CFQ). We look to resolve the curious paradox that older persons
      tend to report fewer failures than younger persons do.

PMID- 25855859
TI  - Monitoring Cluster Ions Derived from Aptamer-Modified Gold Nanofilms under Laser
      Desorption/Ionization for the Detection of Circulating Tumor Cells.
AB  - In this paper, we describe the use of pulsed laser desorption/ionization mass
      spectrometry (LDI-MS) for the detection of tumor cells through the analysis of
      gold cluster ions [Aun](+) from aptamer-modified gold nanofilms (Au NFs). We
      observed not only the transformation of the Au NFs into gold nanoparticles (Au
      NPs) but also the formation of gaseous gold cluster ions ([Au(n)](+); n = 1-5)
      under irradiation with a nanosecond pulsed laser. The size and density of the
      formed Au NPs and the abundance of [Au(n)](+) ions were both highly dependent on
      the thickness of the Au NFs (10-100 nm). Thin Au NFs tended to form highly dense
      Au NPs on the substrate and favored the desorption and ionization of gold cluster
      ions. The signal intensities of the [Au(n)](+) species, monitoring using mass
      spectrometry, decreased upon increasing the thickness of the Au NF from 10 to 100
      nm and after modification with thiolated DNA. Furthermore, we found that Au NFs
      modified with mucin1-binding aptamer (AptMUC1-Au NFs) could selectively enrich
      MCF-7 cells (human breast adenocarcinoma cell line) in blood samples; coupled
      with LDI-MS analysis of the [Au(n)](+) ions, we could detect MCF-7 cells
      selectively in blood samples at abundances as low as 10 cells. This approach
      offers the advantages of high sensitivity, selectivity, and throughput for the
      detection of circulating tumor cells, and has great potential for use as a
      powerful analytical platform for clinical diagnoses of tumor metastasis.

PMID- 25855860
TI  - Phoxonic Hybrid Superlattice.
AB  - We studied experimentally and theoretically the direction-dependent elastic and
      electromagnetic wave propagation in a supported film of hybrid PMMA (poly[methyl
      methacrylate])-TiO2 superlattice (SL). In the direction normal to the layers,
      this one-dimensional periodic structure opens propagation band gaps for both
      hypersonic (GHz) phonons and near-UV photons. The high mismatch of elastic and
      optical impedance results in a large dual phoxonic band gap. The presence of
      defects inherent to the spin-coating fabrication technique is sensitively
      manifested in the band gap region. Utilizing Brillouin light scattering, phonon
      propagation along the layers was observed to be distinctly different from
      propagation normal to them and can, under certain conditions (SL thickness and
      substrate elasticity), reveal the nanomechanical properties of the constituent
      layers. Besides the first realization of unidirectional phoxonic behavior, hybrid
      (soft-hard) periodic materials are a promising simple platform for opto-acoustic
      interactions and applications such as filters and Bragg mirrors. 

PMID- 25855861
TI  - Evaluation of the protective capacity of baseball helmets for concussive impacts.
AB  - The purpose of this research was to examine how four different types of baseball
      helmets perform for baseball impacts when performance was measured using
      variables associated with concussion. A helmeted Hybrid III headform was impacted
      by a baseball, and linear and rotational acceleration as well as maximum
      principal strain were measured for each impact condition. The method was
      successful in distinguishing differences in design characteristics between the
      baseball helmets. The results indicated that there is a high risk of concussive
      injury from being hit by a ball regardless of helmet worn. 

PMID- 25855862
TI  - Primary uterine T-cell lymphoma with metastasis in an Atlantic spotted dolphin
      (Stenella frontalis), Canary Islands, Spain.
AB  - We describe gross, histopathologic, and immunonocytologic features of a primary
      uterine T-cell lymphoma with multiple metastases in an adult female Atlantic
      spotted dolphin (Stenella frontalis). Neoplastic T-cell lymphocytes (CD3+)
      partially effaced the uterus, ovaries, mesosalpinx, and urinary bladder and
      variably infiltrated abdominal and thoracic organs. Herpesvirus and morbillivirus
      PCR were negative. 

PMID- 25855865
TI  - Pain management in cancer survivorship.
AB  - BACKGROUND: The number of patients surviving cancer disease has increased in last
      decades. Consequently, an emerging population with different needs due to long
      term or late effects of cancer disease and/or treatment, e.g. chronic pain, is of
      major concern. EPIDEMIOLOGY: Chronic pain is one of the main problems in this
      population and prevalence varies between 16% and 50%. Most information derives
      from breast cancer patients assessed by surveys from national or local
      institutional databases. A Danish population-based survey estimated that 41.5% of
      all cancer survivors reported chronic pain. PAIN ETIOLOGY: Neuropathic pain seems
      to be the major pain etiology in cancer survivors and therefore adjuvant
      analgesics should be the first choice of analgesic treatment. CONTEXT: This
      article addresses the central aspects of pain epidemiology, mechanisms and the
      frequent pain syndromes met in cancer survivors. Pain management strategies are
      discussed according to the biopsychosocial model and with the rapidly growing
      number of cancer survivors the establishment of multidisciplinary clinics as a
      part of comprehensive cancer centers are proposed.

PMID- 25855864
TI  - Ultrasensitive rapid detection of human serum antibody biomarkers by biomarker
      capturing viral nanofibers.
AB  - Candida albicans (C. albicans) infection causes high mortality rates within
      cancer patients. Due to the low sensitivity of the current diagnosis systems, a
      new sensitive detection method is needed for its diagnosis. Toward this end, here
      we exploited the capability of genetically displaying two functional peptides,
      one responsible for recognizing the biomarker for the infection (antisecreted
      aspartyl proteinase 2 IgG antibody) in the sera of cancer patients and another
      for binding magnetic nanoparticles (MNPs), on a single filamentous fd phage, a
      human-safe bacteria-specific virus. The resultant phage is first decorated with
      MNPs and then captures the biomarker from the sera. The phage-bound biomarker is
      then magnetically enriched and biochemically detected. This method greatly
      increases the sensitivity and specificity of the biomarker detection. The average
      detection time for each serum sample is only about 6 h, much shorter than the
      clinically used gold standard method, which takes about 1 week. The detection
      limit of our nanobiotechnological method is approximately 1.1 pg/mL, about 2
      orders of magnitude lower than that of the traditional antigen-based method,
      opening up a new avenue to virus-based disease diagnosis. 

PMID- 25855866
TI  - Crystal structure and temperature-dependent luminescence characteristics of
      KMg4(PO4)3:Eu(2+) phosphor for white light-emitting diodes.
AB  - The KMg4(PO4)3:Eu(2+) phosphor was prepared by the conventional high temperature
      solid-state reaction. The crystal structure, luminescence and reflectance
      spectra, thermal stability, quantum efficiency and the application for N-UV LED
      were studied respectively. The phase formation and crystal structure of
      KMg4(PO4)3:Eu(2+) were confirmed from the powder X-ray diffraction and the
      Rietveld refinement. The concentration quenching of Eu(2+) in the KMg4(PO4)3 host
      was determined to be 1 mol% and the quenching mechanism was certified to be the
      dipole-dipole interaction. The energy transfer critical distance of as-prepared
      phosphor was calculated to be about 35.84 A. Furthermore, the phosphor exhibited
      good thermal stability and the corresponding activation energy DeltaE was
      reckoned to be 0.24 eV. Upon excitation at 365 nm, the internal quantum
      efficiency of the optimized KMg4(PO4)3:Eu(2+) was estimated to be 50.44%. The
      white N-UV LEDs was fabricated via KMg4(PO4)3:Eu(2+), green-emitting
      (Ba,Sr)2SiO4:Eu(2+), and red-emitting CaAlSiN3:Eu(2+) phosphors with a near-UV
      chip. The excellent color rendering index (Ra = 96) at a correlated color
      temperature (5227.08 K) with CIE coordinates of x = 0.34, y = 0.35 of the WLED
      device indicates that KMg4(PO4)3:Eu(2+) is a promising blue-emitting phosphor for
      white N-UV light emitting diodes (LEDs).

PMID- 25855867
TI  - Developing a guideline to standardize the citation of bioresources in journal
      articles (CoBRA).
AB  - BACKGROUND: Many biomedical publications refer to data obtained from collections
      of biosamples. Sharing such bioresources (biological samples, data, and
      databases) is paramount for the present governance of research. Recognition of
      the effort involved in generating, maintaining, and sharing high quality
      bioresources is poorly organized, which does not encourage sharing. At
      publication level, the recognition of such resources is often neglected and/or
      highly heterogeneous. This is a true handicap for the traceability of bioresource
      use. The aim of this article is to propose, for the first time, a guideline for
      reporting bioresource use in research articles, named CoBRA: Citation of
      BioResources in journal Articles. METHODS: As standards for citing bioresources
      are still lacking, the members of the journal editors subgroup of the Bioresource
      Research Impact Factor (BRIF) initiative developed a standardized and appropriate
      citation scheme for such resources by informing stakeholders about the subject
      and raising awareness among scientists and in science editors' networks, mapping
      this topic among other relevant initiatives, promoting actions addressed to
      stakeholders, launching surveys, and organizing focused workshops. RESULTS: The
      European Association of Science Editors has adopted BRIF's suggestion to
      incorporate statements on biobanks in the Methods section of their guidelines.
      The BRIF subgroup agreed upon a proposed citation system: each individual
      bioresource that is used to perform a study and that is mentioned in the Methods
      section should be cited as an individual "reference [BIORESOURCE]" according to a
      delineated format. The EQUATOR (Enhancing the QUAlity and Transparency Of health
      Research) network mentioned the proposed reporting guideline in their "guidelines
      under development" section. CONCLUSIONS: Evaluating bioresources' use and impact
      requires that publications accurately cite such resources. Adopting the standard
      citation scheme described here will improve the quality of bioresource reporting
      and will allow their traceability in scientific publications, thus increasing the
      recognition of bioresources' value and relevance to research. Please see related
      article: http://dx.doi.org/10.1186/s12916-015-0284-9.

PMID- 25855868
TI  - Cyclic bent allene hydrido-carbonyl complexes of ruthenium: highly active
      catalysts for hydrogenation of olefins.
AB  - A new family of ruthenium complexes bearing the carbodicarbene-type ligand
      "cyclic bent allene" (CBA) have been synthesized from the common precursor
      RuHCl(CO)(PPh3)3. Complexes were evaluated for catalytic activity in the room
      temperature hydrogenation of unactivated olefins and were found to be
      significantly more active than known ruthenium hydrido-carbonyl phosphine or NHC
      complexes. In particular, RuH(OSO2CF3)(CO)(SIMes)(CBA) was found to be among the
      most active hydrogenation catalysts, achieving comparable activity to Crabtree's
      catalyst in the hydrogenation of unactivated trisubstituted olefins and superior
      activity in the hydrogenation of styrene derivatives in side-by-side catalytic
      runs. RuH(OSO2CF3)(CO)(SIMes)(CBA) was also found to be highly active in olefin
      selective hydrogenation in the presence of a variety of unsaturated functional
      groups, and can achieve exceptional diastereoselectivity in functional-group
      directed hydrogenations at very low catalyst loadings. 

PMID- 25855869
TI  - Cathodoluminescence-activated nanoimaging: noninvasive near-field optical
      microscopy in an electron microscope.
AB  - We demonstrate a new nanoimaging platform in which optical excitations generated
      by a low-energy electron beam in an ultrathin scintillator are used as a
      noninvasive, near-field optical scanning probe of an underlying sample. We obtain
      optical images of Al nanostructures with 46 nm resolution and validate the
      noninvasiveness of this approach by imaging a conjugated polymer film otherwise
      incompatible with electron microscopy due to electron-induced damage. The high
      resolution, speed, and noninvasiveness of this "cathodoluminescence-activated"
      platform also show promise for super-resolution bioimaging. 

PMID- 25855870
TI  - Traditional food consumption is associated with better diet quality and adequacy
      among Inuit adults in Nunavut, Canada.
AB  - The Inuit population is undergoing a rapid nutrition transition as a result of
      reduced consumption of traditional foods. This study aims to describe the
      differences in dietary adequacy between non-traditional and traditional eaters
      among Inuit populations in Nunavut, Canada. A cross-sectional survey was
      conducted using a culturally appropriate quantitative food frequency
      questionnaire. Participants included 208 Inuit adults from three isolated
      communities in Nunavut. Traditional eaters consumed a more nutrient-dense diet
      and achieved better dietary adequacy than non-traditional eaters. Traditional
      foods accounted for 7 and 27% of energy intake among non-traditional and
      traditional eaters, respectively. Non-nutrient-dense foods accounted for a
      greater proportion of energy intake in non-traditional eaters; however, these
      were consumed in significant amounts by both the groups (36 and 27% of total
      energy). Consumption of traditional foods is associated with greater diet quality
      and dietary adequacy. Efforts should be made to promote traditional and non
      traditional foods of high-nutritional quality. 

PMID- 25855871
TI  - A prospective, multicenter study assessing the DENTSPLY Implants, OsseoSpeed(TM)
      TX, length 6 mm in the posterior maxilla and mandible: a 1-year follow-up study.
AB  - OBJECTIVE: The aim of this multicenter study was to prospectively assess clinical
      and radiographic outcomes of short implants (length 6 mm) in the posterior region
      and early-loading with splinted-fixed dental prostheses. MATERIALS AND METHODS: A
      total of 45 subjects (77.8% with chronic periodontitis) were enrolled at three
      study sites. In total, 95 implants (diameter 4 mm, length 6 mm; OsseoSpeed(TM)
      4.0 S; DENTSPLY Implants; Molndal, Sweden) were placed, two or three implants per
      subject, using one-stage surgery and loaded with a screw-retained splinted
      ceramic-fixed prosthesis 6 weeks later. Clinical and radiographic examinations
      were performed preoperatively, post-surgery, at loading, and 6 and 12 months
      after prosthesis placement. RESULTS: Four implants failed before loading; all
      other implants showed favorable clinical and radiographic findings throughout the
      observation period (1-year survival and success rate: 95.8%). Postoperative pain
      and swelling were negligible. Mean changes in marginal bone levels measured from
      loading were minimal (0.01 +/- 0.37 and -0.13 +/- 0.46 mm after 6 months and 1
      year, respectively). Bone loss less than 1.00 mm was found in 77.5% implants, and
      bone gain was found in 15.5% implants. Probing depth change less than 2 mm was
      found in 98.7% of the implants between loading and 1-year follow-up. Prosthetic
      complications included one ceramic veneer chipping. CONCLUSION: One-year data
      indicate that the use of 6-mm-long implants is a predictable treatment. This
      provides a good treatment option in situations with limited bone height in
      posterior regions.

PMID- 25855873
TI  - A rare cause of esophagitis with crystal deposition.

PMID- 25855872
TI  - High-resolution structural characterization of Noxa, an intrinsically disordered
      protein, by microsecond molecular dynamics simulations.
AB  - High-resolution characterization of the structure and dynamics of intrinsically
      disordered proteins (IDPs) remains a challenging task. Consequently, a detailed
      understanding of the structural and functional features of IDPs remains limited,
      as very few full-length disordered proteins have been structurally characterized.
      We have performed microsecond-long molecular dynamics (MD) simulations of Noxa,
      the smallest member of the large Bcl-2 family of apoptosis regulating proteins,
      to characterize in atomic-level detail the structural features of a disordered
      protein. A 2.5 MUs MD simulation starting from an unfolded state of the protein
      revealed the formation of a central antiparallel beta-sheet structure flanked by
      two disordered segments at the N- and C-terminal ends. This topology is in
      reasonable agreement with protein disorder predictions and available experimental
      data. We show that this fold plays an essential role in the intracellular
      function and regulation of Noxa. We demonstrate that unbiased MD simulations in
      combination with a modern force field reveal structural and functional features
      of disordered proteins at atomic-level resolution. 

PMID- 25855874
TI  - Increased eligibility for treatment of chronic hepatitis C infection with
      shortened duration of therapy: Implications for access to care and elimination
      strategies in Canada.
AB  - BACKGROUND: All oral, highly effective direct-acting antiviral combinations, such
      as sofosbuvir-ledipasvir, have recently been licensed in Canada but cost as much
      as $67,000 for a 12-week course of therapy, representing a major economic barrier
      to predominately single-payer health care systems such as that found in Ontario.
      In hepatitis C virus (HCV) genotype 1 noncirrhotic patients with a baseline viral
      load of <6 * 10(6) IU/mL, treatment with sofosbuvir-ledipasvir can be shortened
      to eight weeks without compromising >=95% efficacy. The number of HCV-infected
      patients in Ontario eligible for shortened therapy, and the associated cost
      savings, are unknown. The authors propose that treating every patient with
      shortened therapy, regardless of baseline viral load, would lead to significant
      public cost savings and collateral efficiencies, enabling increased HCV treatment
      capacity and cure. METHODS: The present study designed a three-part model to
      investigate the cost of cure per patient and cost savings per patient under three
      eligibility pathways: conservative, permissive and ideal. In the conservative
      model, every patient is treated for 12 weeks regardless of baseline viral load,
      whereas in the permissive model, patients with a baseline viral load <6 * 10(6)
      IU/mL are treated for eight weeks. In the ideal model, every patient receives
      eight weeks of therapy regardless of baseline viral load. Relapsed patients are
      retreated for 12 weeks. Data obtained from the Ontario Public Health Laboratory
      were used to validate the model and generate the outcomes. RESULTS: In Ontario,
      75.34% of HCV genotype 1 patients had a baseline viral load of <6 * 10(6) IU/mL
      and were eligible for shortened therapy. The cost of cure per patient in the
      ideal model was $47,328.44, representing a 29% reduction in the cost of curative
      therapy and 3.5 weeks of shortened treatment duration compared with the
      conservative model. The ideal model generated a cost savings per patient of
      $3,855.17 (8% reduction in treatment cost) and 0.7 weeks of shorter therapy
      compared with the permissive model, and was the shortest and most efficient while
      maintaining a cure rate >=95%. CONCLUSIONS: These results demonstrate that
      recommendations for a shortened treatment course of eight weeks using all-oral
      direct-acting antivirals in HCV genotype 1 noncirrhotic patients, regardless of
      baseline viral load, affords significant public cost savings and, on a population
      level, offers opportunities for expanded HCV treatment and cure.

PMID- 25855876
TI  - Risk factors for mortality in patients with alcoholic hepatitis and assessment of
      prognostic models: A population-based study.
AB  - BACKGROUND: Severe alcoholic hepatitis (AH) is associated with a substantial risk
      for short-term mortality. OBJECTIVES: To identify prognostic factors and validate
      well-known prognostic models in a Canadian population of patients hospitalized
      for AH. METHODS: In the present retrospective study, patients hospitalized for AH
      in Calgary, Alberta, between January 2008 and August 2012 were included. Stepwise
      logistic regression models identified independent risk factors for 90-day
      mortality, and the discrimination of prognostic models (Model for End-stage Liver
      Disease [MELD] and Maddrey discriminant function [DF]) were examined using areas
      under the ROC curves. RESULTS: A total of 122 patients with AH were hospitalized
      during the study period; the median age was 49 years (interquartile range [IQR]
      42 to 55 years) and 60% were men. Median MELD score and Maddrey DF on admission
      were 21 (IQR 18 to 24) and 45 (IQR 26 to 62), respectively. Seventy-three percent
      of patients received corticosteroids and/or pentoxifylline, and the 90-day
      mortality was 17%. Independent predictors of mortality included older age, female
      sex, international normalized ratio, MELD score and Maddrey DF (all P<0.05). For
      discrimination of 90-day mortality, the areas under the ROC curves of the
      prognostic models (MELD 0.64; Maddrey DF 0.68) were similar (P>0.05). At optimal
      cut-offs of >=22 for MELD score and >=37 for Maddrey DF, both models excluded
      death with high certainty (negative predictive values 90% and 96%, respectively).
      CONCLUSIONS: In patients hospitalized for AH, well-known prognostic models can be
      used to predict 90-day mortality, particularly to identify patients with a low
      risk for death.

PMID- 25855877
TI  - Noninvasive methods, including transient elastography, for the detection of liver
      disease in adults with cystic fibrosis.
AB  - BACKGROUND: Liver disease is the third leading cause of mortality in patients
      with cystic fibrosis (CF). However, detection of CF-associated liver disease
      (CFLD) is challenging. OBJECTIVE: To evaluate the diagnostic performance of
      noninvasive methods for the detection of CFLD with a focus on transient
      elastography (TE). METHODS: Patients at the Adult CF Clinic of Calgary and
      Southern Alberta (n=127) underwent liver stiffness measurement (LSM) by TE using
      the FibroScan (FS, Ecosens, France) M probe; aspartate aminotransferase to
      platelet ratio index (APRI) and FibroTest (FT) scores were also calculated. The
      diagnostic performance of these tools for the detection of CFLD (defined as two
      or more the following criteria: abnormal liver biochemistry, hepatomegaly or
      sonographic abnormalities other than steatosis) were compared using the area
      under ROC curves. RESULTS: Forty-seven percent of the cohort was male. The median
      age was 27 years (interquartile range [IQR] 22 to 37 years) and body mass index
      21 kg/m(2) (IQR 19 kg/m(2) to 23 kg/m(2)); 25% of patients were on
      ursodeoxycholic acid and 12% had undergone lung transplantation. The prevalence
      of CFLD was 14% (n=18). FS was successful in all patients; one (0.8%) patient had
      poorly reliable results (IQR/M >30% and LSM >=7.1 kPa). Compared with patients
      without CFLD (n=109), individuals with CFLD had higher median LSM according to FS
      (3.9 kPa [IQR 3.4 to 4.9 kPa] versus 6.4 kPa [IQR 4.4 to 8.0 kPa]), APRI (0.24
      [IQR 0.17 to 0.31] versus 0.50 [IQR 0.22 to 1.18]) and FT scores (0.08 [IQR 0.05
      to 1.5] versus 0.18 [IQR 0.11 to 0.35]; all P<0.05). Area under ROC curve for FS,
      APRI and FT for the detection of CFLD were 0.78 (95% CI 0.65 to 0.92), 0.72 (95%
      CI 0.56 to 0.87) and 0.76 (95% CI 0.62 to 0.90) (P not significant). At a
      threshold of >5.2 kPa, the sensitivity, specificity, positive and negative
      predictive values of LSM according to FS for detecting CFLD were 67%, 83%, 40%
      and 94%, respectively. CONCLUSIONS: FS, APRI and FT were useful noninvasive
      methods for detecting CFLD in adults.

PMID- 25855878
TI  - Venous thromboprophylaxis in gastrointestinal bleeding.
AB  - OBJECTIVE: To study the use of venous thromboembolism (VTE) prophylaxis and the
      incidence of thrombotic events in patients with acute gastrointestinal (GI)
      bleeding. METHODS: Individuals admitted with a primary diagnosis of a GI bleed
      along with any endoscopically confirmed source (over a two-year period) were
      included. Patient comorbidity and data regarding anticoagulation or antiplatelet
      agent use before hospitalization were collected, in addition to type of VTE
      prophylaxis and duration of treatment. The primary end point was the development
      of VTE (deep vein thrombosis or pulmonary embolism) within one year of
      presentation. RESULTS: Data from 504 patients admitted with GI bleeding were
      eligible for review. The total number of VTE events was 20 (4%) while the
      mortality rate during hospitalization was 4.6%; 397 patients were not given VTE
      prophylaxis during their hospitalization. Of the patients who were given VTE
      prophylaxis, 68 received prophylactic heparin or heparin derivatives during their
      admission. One hundred sixty-five patients had at least one other significant
      risk factor for VTE including recent or subsequent surgery, past thrombotic event
      or malignancy. The incidence of thrombosis in those with significant risk factors
      for VTE was significantly higher than those without (8.5% versus 1.8%; P=0.0009).
      Overall, there was no significant difference in thrombotic events between
      individuals receiving pharmacological prophylaxis (1.2%) and those who did not
      (2.8%) (P=0.4). CONCLUSION: Overall, VTE prophylaxis did not significantly affect
      thrombotic events in patients admitted for an active GI bleed.

PMID- 25855879
TI  - Adult lactose digestion status and effects on disease.
AB  - BACKGROUND: Adult assimilation of lactose divides humans into dominant lactase
      persistent and recessive nonpersistent phenotypes. OBJECTIVES: To review three
      medical parameters of lactose digestion, namely: the changing concept of lactose
      intolerance; the possible impact on diseases of microbial adaptation in lactase
      nonpersistent populations; and the possibility that the evolution of lactase has
      influenced some disease pattern distributions. METHODS: A PubMed, Google Scholar
      and manual review of articles were used to provide a narrative review of the
      topic. RESULTS: The concept of lactose intolerance is changing and merging with
      food intolerances. Microbial adaptation to regular lactose consumption in lactase
      nonpersistent individuals is supported by limited evidence. There is evidence
      suggestive of a relationship among geographical distributions of latitude,
      sunhine exposure and lactase proportional distributions worldwide. DISCUSSION:
      The definition of lactose intolerance has shifted away from association with
      lactose maldigestion. Lactose sensitivity is described equally in lactose
      digesters and maldigesters. The important medical consequence of withholding
      dairy foods could have a detrimental impact on several diseases; in addition,
      microbial adaptation in lactase-nonpersistent populations may alter risk for some
      diseases. There is suggestive evidence that the emergence of lactase persistence,
      together with human migrations before and after the emergence of lactase
      persistence, have impacted modern-day diseases. CONCLUSIONS: Lactose maldigestion
      and lactose intolerance are not synonymous. Withholding dairy foods is a poor
      method to treat lactose intolerance. Further epidemiological work could shed
      light on the possible effects of microbial adaptation in lactose maldigesters.
      The evolutionary impact of lactase may be still ongoing.

PMID- 25855881
TI  - Re: PC Adams. Genetic testing for hemochromatosis: Diagnostic or confirmatory
      test for iron overload? Can J Gastroenterol Hepatol 2015;29(1):15-6.

PMID- 25855880
TI  - Fecal calprotectin use in inflammatory bowel disease and beyond: A mini-review.
AB  - Given the number of inflammatory disorders affecting the gastrointestinal tract
      directly and indirectly, coupled with the considerable overlap with functional
      disorders, it is evident that more useful noninvasive diagnostic tests are
      required to aid with diagnosis. If these tests can also have some utility for
      individual patient follow-up in terms of disease activity and response to
      treatment, as well as providing forewarning of disease relapse, it would be
      extremely useful information for the clinician. One recently described test that
      may fulfill several of these attributes is based on leakage of a mononuclear cell
      cytoplasmic protein, calprotectin, along the intestinal tract, which can then be
      quantified in feces. This has been used to distinguish patients exhibiting
      symptoms of irritable bowel syndrome from patients with inflammatory bowel
      disease, with a measure of success greater than with currently used techniques.
      The present article summarizes the experience with this test used in inflammatory
      bowel disease, as well as a variety of gastrointestinal disorders.

PMID- 25855883
TI  - Usual Intake Distribution of Vitamins and Prevalence of Inadequacy in a Large
      Sample of Iranian At-Risk Population: Application of NCI Method.
AB  - OBJECTIVE: This study provides an assessment of usual intake distribution of
      vitamins and estimating prevalence of inadequacy and excess among a large
      representative sample of middle-aged and elderly people in central regions of
      Iran. DESIGN: A cross-sectional study that is a second follow-up to the Isfahan
      Cohort Study (ICS). SETTING: The study setting included urban and rural areas
      from 3 cities (Isfahan, Najafabad, and Arak) in central regions of Iran.
      SUBJECTS: Subjects included 1922 people aged 40 years and older, with a mean age
      of 55.9 +/- 10.6; 50.4% were male and the majority (79.3%) were urban. MEASURES
      AND ANALYSIS: Dietary intakes were collected using a 24-hour recall and 2 food
      records. Distribution of vitamins intake was estimated using traditional and
      national cancer institute (NCI) methods. The proportion of subjects at risk of
      vitamin intake inadequacy or excess was estimated using the estimated average
      requirement (EAR) cut-point method and the tolerable upper intake levels (UL)
      index. RESULTS: There were differences between values obtained from traditional
      and NCI methods, particularly in the lower and upper percentiles of the intake
      distribution. High prevalence of inadequacies for vitamins A, D, E, B2, B3
      (especially among females), and B9 was observed. Significant gender differences
      were found in terms of inadequate intakes for vitamins A, B1, B2, B3, B6, B9,
      B12, and C (p < 0.05). CONCLUSION: Imbalanced vitamin intake was observed in the
      middle-aged and elderly Iranian population. Nutritional interventions
      particularly through population-based educational programs in order to improve
      diet variety and consume nutrient supplements may be necessary.

PMID- 25855882
TI  - Myocardial Infarction, Stroke, and Mortality in cART-Treated HIV Patients on
      Statins.
AB  - Despite combination antiretroviral therapy (cART), people living with HIV (PLWH)
      continue to have more systemic inflammation and metabolic disturbances than the
      general population. These risk factors for atherosclerosis and organ dysfunction
      may be ameliorated by statins. We retrospectively analyzed 438 cART treated PLWH
      from the Nutrition For Healthy Living (NFHL) cohort to determine the association
      between statins and myocardial infarction (MI), stroke, and all-cause mortality
      as a composite. We used Cox proportional hazards regression as our main analysis.
      The average age was 44 years, 32% were women, and 67 of the 438 subjects used
      statins. There was no association between statins and our composite endpoint in
      two separate models [1.26 (0.57-2.79) in statin history model and 0.93 (0.65
      1.32) per year in statin duration model]. The composite outcome was significantly
      associated with CD4 count, age, and smoking status in both models. CD4 count
      remained significant even after exclusion of mortality from the composite
      (HR=0.88, p=0.02). Confounding control via propensity scoring and multiple
      imputations did not change the results. Statins did not have an effect on MI,
      stroke, and mortality. Interestingly, CD4 count appears to be an important
      predictor of these outcomes, even after exclusion of death from the composite. 

PMID- 25855884
TI  - The Adult Calfactant in Acute Respiratory Distress Syndrome Trial.
AB  - BACKGROUND: Surfactant has been shown to be dysfunctional in ARDS, and exogenous
      surfactant has proven effective in many forms of neonatal and pediatric acute
      lung injury (ALI). In view of the positive results of our studies in children
      along with evidence that surfactant-associated protein B containing
      pharmaceutical surfactants might be more effective, we designed a
      multiinstitutional, randomized, controlled, and masked trial of calfactant, a
      calf lung surfactant, in adults and children with ALI/ARDS due to direct lung
      injury. METHODS: Adult subjects within 48 h of initiation of mechanical
      ventilation for direct ARDS were randomized to receive up to three interventions
      with instilled calfactant vs air placebo. The primary outcome was 90-day all
      cause mortality. RESULTS: Three hundred seventeen subjects were enrolled, 308 of
      whom could be evaluated. There were no significant baseline differences between
      groups. Calfactant administration was not associated with improved survival,
      lengths of stay, or oxygenation. Calfactant instillation was frequently
      associated with transient hypoxia and hypotension. The study was stopped at the
      first interim analysis at the sponsor's request. CONCLUSIONS: Administration of
      calfactant was not associated with improved oxygenation or longer-term benefits
      relative to placebo in this randomized, controlled, and masked trial. At present,
      exogenous surfactant cannot be recommended for routine clinical use in ARDS.
      TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00682500; URL:
      www.clinicaltrials.gov.

PMID- 25855886
TI  - Versatile robotic probe calibration for position tracking in ultrasound imaging.
AB  - Within the field of ultrasound-guided procedures, there are a number of methods
      for ultrasound probe calibration. While these methods are usually developed for a
      specific probe, they are in principle easily adapted to other probes. In
      practice, however, the adaptation often proves tedious and this is impractical in
      a research setting, where new probes are tested regularly. Therefore, we
      developed a method which can be applied to a large variety of probes without
      adaptation. The method used a robot arm to move a plastic sphere submerged in
      water through the ultrasound image plane, providing a slow and precise movement.
      The sphere was then segmented from the recorded ultrasound images using a MATLAB
      programme and the calibration matrix was computed based on this segmentation in
      combination with tracking information. The method was tested on three very
      different probes demonstrating both great versatility and high accuracy. 

PMID- 25855885
TI  - Response of head and neck squamous cell carcinoma cells carrying PIK3CA mutations
      to selected targeted therapies.
AB  - IMPORTANCE: The PIK3CA mutation is one of the most common mutations in head and
      neck squamous cell carcinoma (HNSCC). Through this research we attempt to elicit
      the role of oncogene dependence and effects of targeted therapy on this PIK3CA
      mutation. OBJECTIVES: (1) To determine the role of oncogene dependence on PIK3CA
      one of the more common and targetable oncogenes in HNSCC, and (2) to evaluate the
      consequence of this oncogene on the effectiveness of newly developed targeted
      therapies. DESIGN, SETTING, AND PARTICIPANTS: This was a cell culture-based, in
      vitro study performed at an academic research laboratory assessing the viability
      of PIK3CA-mutated head and neck cell lines when treated with targeted therapy.
      EXPOSURES: PIK3CA-mutated head and neck cell lines were treated with 17-AAG, GDC
      0941, trametinib, and BEZ-235. MAIN OUTCOMES AND MEASURES: Assessment of cell
      viability of HNSCC cell lines characterized for PIK3CA mutations or SCC25 cells
      engineered to express the PIK3CA hotspot mutations E545K or H1047R. RESULTS:
      Surprisingly, in engineered cell lines, the hotspot E545K and H1047R mutations
      conferred increased, rather than reduced, IC50 assay measurements when treated
      with the respective HSP90, PI3K, and MEK inhibitors, 17-AAG, GDC-0941, and
      trametinib, compared with the SCC25 control cell lines. When treated with BEZ
      235, H1047R-expressing cell lines showed increased sensitivity to inhibition
      compared with control, whereas those expressing E545K showed slightly increased
      sensitivity of unclear significance. CONCLUSIONS AND RELEVANCE: (1) The PIK3CA
      mutations within our engineered cell model did not lead to enhanced oncogene
      dependent cell death when treated with direct inhibition of the PI3K enzyme yet
      did show increased sensitivity compared with control with dual PI3K/mTOR
      inhibition. (2) Oncogene addiction to PIK3CA hotspot mutations, if it occurs, is
      likely to evolve in vivo in the context of additional molecular changes that
      remain to be identified. Additional study is required to develop new model
      systems and approaches to determine the role of targeted therapy in the treatment
      of PI3K-overactive HNSCC tumors.

PMID- 25855887
TI  - Histological and Ultrastructure Analysis of Dentin Dysplasia Type I in Primary
      Teeth: A Case Report.
AB  - Dentin dysplasia type I (DD-I) is a rare human dentin disorder that may affect
      both the primary and permanent dentitions. The teeth present crowns with normal
      morphology but short or absent roots. Pulp chamber obliteration and early
      exfoliation of primary teeth are also observed. We describe herein the typical
      and atypical features of DD-I presented by a 6-year-old patient, the diagnostic
      rationale and assessment emphasizing the histological and scanning electron
      microscopic analysis and the therapeutic approach. The DD-I diagnosis in patients
      in the mixed dentition period is challenging, especially when only some teeth are
      affected. 

PMID- 25855888
TI  - Processing of different types of social threat in shyness: Preliminary findings
      of distinct functional neural connectivity.
AB  - Current theory suggests that the processing of different types of threat is
      supported by distinct neural networks. Here we tested whether there are distinct
      neural correlates associated with different types of threat processing in
      shyness. Using fMRI and multivariate techniques, we compared neural responses and
      functional connectivity during the processing of imminent (i.e., congruent
      angry/angry face pairs) and ambiguous (i.e., incongruent angry/neutral face
      pairs) social threat in young adults selected for high and low shyness. To both
      types of threat processing, non-shy adults recruited a right medial prefrontal
      cortex (mPFC) network encompassing nodes of the default mode network involved in
      automatic emotion regulation, whereas shy adults recruited a right dorsal
      anterior cingulate cortex (dACC) network encompassing nodes of the frontoparietal
      network that instantiate active attentional and cognitive control. Furthermore,
      in shy adults, the mPFC interacted with the dACC network for ambiguous threat,
      but with a distinct network encompassing nodes of the salience network for
      imminent threat. These preliminary results expand our understanding of right mPFC
      function associated with temperamental shyness. They also provide initial
      evidence for differential neural networks associated with shy and non-shy
      profiles in the context of different types of social threat processing. 

PMID- 25855889
TI  - A fluorescent chemosensor for Hg(2+) and Cd(2+) ions in aqueous medium under
      physiological pH and its applications in imaging living cells.
AB  - A new BODIPY derivative with 2,2'-(ethane-1,2-diylbis(oxy))bis(N,N-bis(pyridine-2
      ylmethyl)aniline unit as the metal receptor has been designed and synthesized.
      The dye selectively detects either Cd(2+) or Hg(2+) ions in the presence of hosts
      of other biologically important and environmentally relevant metal ions in
      aqueous medium at physiological pH. Binding of metal ions causes a change in the
      emission behavior of the dye from weakly fluorescent to highly fluorescent.
      Confocal microscopic experiments validate that the dye can be used to identify
      changes in either Hg(2+) or Cd(2+) levels in living cells. 

PMID- 25855891
TI  - Diagnosis of ALK-positive anaplastic large cell lymphoma based on CD30 testing.

PMID- 25855890
TI  - Early recognition of ipilimumab-related autoimmune hypophysitis in patients with
      metastatic melanoma: Case studies and recommendations for management.
AB  - Ipilimumab is a human anti-CTLA-4 monoclonal antibody recently approved for the
      treatment of advanced melanoma. Stimulation of T-cell activity unmasks antitumor
      activity, but can cause immune-related adverse events. Autoimmune hypophysitis is
      of particular importance because its presentation can be subtle but life
      threatening. We present two cases where early recognition of ipilimumab-related
      autoimmune hypophysitis led to timely intervention and low subsequent morbidity,
      without compromise of antitumor effects. We provide recommendations for detection
      and management of this potentially life-threatening complication of ipilimumab.

PMID- 25855892
TI  - Undiagnosed mycosis fungoides with transformation to large cell peripheral T-cell
      lymphoma.

PMID- 25855893
TI  - Commentary: diagnostic dilemmas that impact treatment decisions in lymphoma.

PMID- 25855894
TI  - A signet-ring cell melanoma arising from a medium-sized congenital melanocytic
      nevus in an adult: A case report and literature review.
AB  - Patients with congenital nevus, especially giant congenital melanocytic nevus
      (CMN) measuring >20 cm, are known to be at elevated risk of developing melanomas,
      especially during the first and second decades of life. Melanomas rarely develop
      in patients with small and medium-sized CMNs, but if they do, they occur during
      the fourth and fifth decades of life. We present a case of a rapidly enlarging
      signet-ring cell melanoma (over 3 months) that arose from a medium-sized CMN in a
      57-year-old Japanese man. Only 11 other cases of signet-ring cell melanomas at
      the primary site have been reported. On the basis of morphology alone, it is
      difficult to diagnose a nodule appearing in a CMN as a signet-ring cell melanoma,
      because even a benign melanocytic nevus can appear as signet-ring cell
      morphology. Moreover, a rapidly growing proliferative nodule (PN) more often
      develops in a CMN than melanoma; PNs may at times exhibit enough atypia to be
      comparable to melanomas. In our case, loss of p16 expression in the melanoma
      distinguished it from the nevus cells and was helpful in making the correct
      diagnosis. Clinical information, such as the patient's age, was also useful in
      establishing the diagnosis. 

PMID- 25855895
TI  - HM30181 Derivatives as Novel Potent and Selective Inhibitors of the Breast Cancer
      Resistance Protein (BCRP/ABCG2).
AB  - The breast cancer resistance protein (BCRP, ABCG2) belongs to the superfamily of
      ATP binding-cassette (ABC) proteins. In addition to other physiological
      functions, it transports potentially cell-damaging compounds out of the cell
      using the energy from ATP hydrolysis. Certain tumors overexpressing BCRP were
      found to become resistant against various anticancer drugs. In previous work, we
      found that tariquidar analogues lacking the tetrahydroisoquinoline moiety
      selectively inhibit BCRP. In the present study, we synthesized 21 derivatives of
      the third-generation P-gp inhibitor HM30181, which is structurally related to
      tariquidar. The compounds were tested for their inhibitory activities against
      BCRP and screened against P-glycoprotein (P-gp, ABCB1) and multidrug resistance
      protein 1 (MRP1, ABCC1) to confirm the selectivity toward BCRP. The most potent
      compounds are selective toward BCRP and 2-fold more potent than the reference
      Ko143. Qualitative structure-activity relationship (SAR) analysis revealed that
      the presence of a methoxy group in the ortho or para position of at least one
      phenyl ring is beneficial for inhibitory activity. Furthermore, the cytotoxicity
      and multidrug resistance (MDR)-reversal ability of selected compounds were
      investigated. It was shown that they have a low cytotoxicity and the ability to
      reverse the BCRP-mediated SN-38 resistance. 

PMID- 25855896
TI  - Dealing with female sexuality: training, attitude, and practice of obstetrics and
      gynecology residents from a developing country.
AB  - INTRODUCTION: There is little research on how obstetrics and gynecology (Ob/Gyn)
      residents deal with female sexuality, especially during pregnancy. AIM: The aim
      of this study was to assess the training, attitude, and practice of Ob/Gyn
      residents about sexuality. METHODS: A cross-sectional survey of Brazilian Ob/Gyn
      residents enrolling in an online sexology course was conducted. A questionnaire
      assessed their training in sexuality during medical school and residency and
      their attitude and practice on sexual issues during pregnancy. MAIN OUTCOME
      MEASURES: Training, attitude, and practice of Ob/Gyn residents regarding
      sexuality were the main outcome measures. RESULTS: A total of 197 residents, from
      21 different programs, answered the online questionnaire. Mean age was 27.9 +/-
      2.2, most were female (87%), single (79%), and had graduated in the last 5 years
      (91%). Almost two-thirds (63%) stated that they did not receive any training at
      all and 28% reported having only up to 6 hours of training about sexuality in
      medical school. Approximately half of the respondents (49%) stated that they had
      received no formal training about sexuality during their residency up to that
      moment and 29% had received <=6 hours of training. Over half (56%) never or
      rarely took a sexual history, 51% stated that they did not feel competent or
      confident to answer their pregnant patients' questions about sexuality, and 84%
      attributed their difficulties in dealing with sexual complaints to their lack of
      specific knowledge on the topic. CONCLUSION: The vast majority of Brazilian
      Ob/Gyn residents enrolling in a sexuality course had little previous formal
      training on this topic in medical school and during their residency programs.
      Most residents do not take sexual histories of pregnant patients, do not feel
      confident in answering questions about sexuality in pregnancy, and attribute
      these difficulties to lack of knowledge. These findings point to a clear need for
      additional training in sexuality among Brazilian Ob/Gyn residents.

PMID- 25855897
TI  - A Multicenter Evaluation of Off-Label Medication Use and Associated Adverse Drug
      Reactions in Adult Medical ICUs.
AB  - OBJECTIVE: Prior research indicates that off-label use is common in the ICU;
      however, the safety of off-label use has not been assessed. The study objective
      was to determine the prevalence of adverse drug reactions associated with off
      label use and evaluate off-label use as a risk factor for the development of
      adverse drug reactions in an adult ICU population. DESIGN: Multicenter,
      observational study SETTING: : Medical ICUs at three academic medical centers.
      PATIENTS: Adult patients (age >= 18 yr old) receiving medication therapy.
      INTERVENTIONS: All administered medications were evaluated for Food and Drug
      Administration-approved or off-label use. Patients were assessed daily for the
      development of an adverse drug reaction through active surveillance. Three
      adverse drug reaction assessment instruments were used to determine the
      probability of an adverse drug reaction resulting from drug therapy. Severity and
      harm of the adverse drug reaction were also assessed. Cox proportional hazard
      regression was used to identify a set of covariates that influenced the rate of
      adverse drug reactions. MEASUREMENTS AND MAIN RESULTS: Overall, 1,654 patient
      days (327 patients) and 16,391 medications were evaluated, with 43% of
      medications being used off-label. One hundred and sixteen adverse drug reactions
      were categorized dichotomously (Food and Drug Administration or off-label), with
      56% and 44% being associated with Food and Drug Administration-approved and off
      label use, respectively. The number of adverse drug reactions for medications
      administered and the number of harmful and severe adverse drug reactions did not
      differ for medications used for Food and Drug Administration-approved or off
      label use (0.74% vs 0.67%; p = 0.336; 33 vs 31 events, p = 0.567; 24 vs 24
      events, p = 0.276). Age, sex, number of high-risk medications, number of off
      label medications, and severity of illness score were included in the Cox
      proportional hazard regression. It was found that the rate of adverse drug
      reactions increases by 8% for every one additional off-label medication (hazard
      ratio = 1.08; 95% CI, 1.018-1.154). CONCLUSION: Although adverse drug reactions
      do not occur more frequently with off-label use, adverse drug reaction risk
      increases with each additional off-label medication used.

PMID- 25855898
TI  - Drug Repurposing Screen Identifies Foxo1-Dependent Angiopoietin-2 Regulation in
      Sepsis.
AB  - OBJECTIVE: The recent withdrawal of a targeted sepsis therapy has diminished
      pharmaceutical enthusiasm for developing novel drugs for the treatment of sepsis.
      Angiopoietin-2 is an endothelial-derived protein that potentiates vascular
      inflammation and leakage and may be involved in sepsis pathogenesis. We screened
      approved compounds for putative inhibitors of angiopoietin-2 production and
      investigated underlying molecular mechanisms. DESIGN: Laboratory and animal
      research plus prospective placebo-controlled randomized controlled trial
      (NCT00529139) and retrospective analysis (NCT00676897). SETTING: Research
      laboratories of Hannover Medical School and Harvard Medical School. PATIENTS:
      Septic patients/C57Bl/6 mice and human endothelial cells. INTERVENTIONS: Food and
      Drug Administration-approved library screening. MEASUREMENTS AND MAIN RESULTS: In
      a cell-based screen of more than 650 Food and Drug Administration-approved
      compounds, we identified multiple members of the 3-hydroxy-3-methyl-glutaryl-CoA
      reductase inhibitor drug class (referred to as statins) that suppressed
      angiopoietin-2. Simvastatin inhibited 3-hydroxy-3-methyl-glutaryl-CoA reductase,
      which in turn activated PI3K-kinase. Downstream of this signaling, PI3K-dependent
      phosphorylation of the transcription factor Foxo1 at key amino acids inhibited
      its ability to shuttle to the nucleus and bind cis-elements in the angiopoietin-2
      promoter. In septic mice, transient inhibition of angiopoietin-2 expression by
      liposomal siRNA in vivo improved absolute survival by 50%. Simvastatin had a
      similar effect, but the combination of angiopoietin-2 siRNA and simvastatin
      showed no additive benefit. To verify the link between statins and angiopoietin-2
      in humans, we performed a pilot matched case-control study and a small randomized
      placebo-controlled trial demonstrating beneficial effects on angiopoietin-2.
      CONCLUSIONS: 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors may operate
      through a novel Foxo1-angiopoietin-2 mechanism to suppress de novo production of
      angiopoietin-2 and thereby ameliorate manifestations of sepsis. Given
      angiopoietin-2's dual role as a biomarker and candidate disease mediator, early
      serum angiopoietin-2 measurement may serve as a stratification tool for future
      trials of drugs targeting vascular leakage.

PMID- 25855899
TI  - Association Between Arterial Hyperoxia and Outcome in Subsets of Critical
      Illness: A Systematic Review, Meta-Analysis, and Meta-Regression of Cohort
      Studies.
AB  - OBJECTIVE: Oxygen is vital during critical illness, but hyperoxia may harm
      patients. Our aim was to systematically evaluate the methodology and findings of
      cohort studies investigating the effects of hyperoxia in critically ill adults.
      DATA SOURCE: A meta-analysis and meta-regression analysis of cohort studies
      published between 2008 and 2015 was conducted. Electronic databases of MEDLINE,
      EMBASE, and Web of Science were systematically searched for the keywords
      hyperoxia and mortality or outcome. STUDY SELECTION: Publications assessing the
      effect of arterial hyperoxia on outcome in critically ill adults (>= 18 yr)
      admitted to critical care units were eligible. We excluded studies in patients
      with chronic obstructive pulmonary disease, extracorporeal life support or
      hyperbaric oxygen therapy, and animal studies. Due to a lack of data, no studies
      dedicated to patients with acute lung injury, sepsis, shock, or multiple trauma
      could be included. DATA EXTRACTION: Studies were included independent of
      admission diagnosis and definition of hyperoxia. The primary outcome measure was
      in-hospital mortality, and results were stratified for relevant subgroups
      (cardiac arrest, traumatic brain injury, stroke, post-cardiac surgery, and any
      mechanical ventilation). The effects of arterial oxygenation on functional
      outcome, long-term mortality, and discharge variables were studied as secondary
      outcomes. DATA SYNTHESIS: Twenty-four studies were included of which five studies
      were only for a subset of the analyses. Nineteen studies were pooled for meta
      analyses and showed that arterial hyperoxia during admission increases hospital
      mortality: adjusted odds ratio, 1.21 (95% CI, 1.08-1.37) (p = 0.001). Functional
      outcome measures were diverse and generally showed a more favorable outcome for
      normoxia. CONCLUSIONS: In various subsets of critically ill patients, arterial
      hyperoxia was associated with poor hospital outcome. Considering the substantial
      heterogeneity of included studies and the lack of a clinical definition, more
      evidence is needed to provide optimal oxygen targets to critical care physicians.

PMID- 25855900
TI  - Impact of Sepsis Classification and Multidrug-Resistance Status on Outcome Among
      Patients Treated With Appropriate Therapy.
AB  - OBJECTIVE: To assess the impact of sepsis classification and multidrug-resistance
      status on outcome in patients receiving appropriate initial antibiotic therapy.
      DESIGN: A retrospective cohort study. SETTING: Barnes-Jewish Hospital, a 1,250
      bed teaching hospital. PATIENTS: Individuals with Enterobacteriaceae sepsis,
      severe sepsis, and septic shock who received appropriate initial antimicrobial
      therapy between June 2009 and December 2013. INTERVENTIONS: Clinical outcomes
      were compared according to multidrug-resistance status, sepsis classification,
      demographics, severity of illness, comorbidities, and antimicrobial treatment.
      MEASUREMENTS AND MAIN RESULTS: We identified 510 patients with Enterobacteriaceae
      bacteremia and sepsis, severe sepsis, or septic shock. Sixty-seven patients
      (13.1%) were nonsurvivors. Mortality increased significantly with increasing
      severity of sepsis (3.5%, 9.9%, and 28.6%, for sepsis, severe sepsis, and septic
      shock, respectively; p < 0.05). Time to antimicrobial therapy was not
      significantly associated with outcome. Acute Physiology and Chronic Health
      Evaluation II was more predictive of mortality than age-adjusted Charlson
      comorbidity index. Multidrug-resistance status did not result in excess
      mortality. Length of ICU and hospital stay increased with more severe sepsis. In
      multivariate logistic regression analysis, African-American race, sepsis
      severity, Acute Physiology and Chronic Health Evaluation II score, solid-organ
      cancer, cirrhosis, and transfer from an outside hospital were all predictors of
      mortality. CONCLUSIONS: Our results support sepsis severity, but not multidrug
      resistance status as being an important predictor of death when all patients
      receive appropriate initial antibiotic therapy. Future sepsis trials should
      attempt to provide appropriate antimicrobial therapy and take sepsis severity
      into careful account when determining outcomes.

PMID- 25855901
TI  - The Association Between Nutritional Adequacy and Long-Term Outcomes in Critically
      Ill Patients Requiring Prolonged Mechanical Ventilation: A Multicenter Cohort
      Study.
AB  - OBJECTIVE: To examine the association between short-term nutritional adequacy
      received while in the ICU and long-term outcomes including 6-month survival and
      health-related quality of life in critically ill patients requiring prolonged
      mechanical ventilation. DESIGN: Retrospective analysis of data prospectively
      collected in the context of a multicenter randomized controlled trial. SETTING:
      An international sample of ICUs. PATIENTS: Adult patients who were mechanically
      ventilated for more than 8 days in the ICU. INTERVENTIONS: None. MEASUREMENTS AND
      MAIN RESULTS: Nutritional adequacy was obtained from the average proportion of
      prescribed calories received over the amount prescribed during the first 8 days.
      Survival status and health-related quality of life as assessed using the Short
      Form 36 v2 were obtained at 3- and 6 months post ICU admission. Of the 1,223
      patients enrolled in the randomized controlled trial, 475 met the inclusion
      criteria for this study. At 6-month follow-up, 302 of the 475 patients (64%) were
      alive. Survival time in those who received low nutritional adequacy was
      significantly shorter than those who received high nutritional adequacy while
      adjusting for important covariates (adjusted hazard ratio, 1.7; 95% CI, 1.1-2.6).
      At 3-month follow-up, a 25% increase in nutritional adequacy was associated with
      improvements in Physical Functioning and Role Physical of 7.3 (p = 0.02) and 8.3
      (p = 0.004) points, respectively. At 6-month follow-up, adjusted increases in
      Physical Functioning and Role Physical scores for every 25% increase in nutrition
      adequacy became smaller and were no longer statistically significant (adjusted
      estimate for Physical Functioning = 4.2, p = 0.14; for Role Physical = 3.2, p =
      0.25). CONCLUSIONS: Greater amounts of nutritional intake received during the
      first week in the ICU were associated with longer survival time and faster
      physical recovery to 3 months but not 6 months post ICU discharge in critically
      ill patients requiring prolonged mechanical ventilation. Current recommendations
      to underfeed critically ill patients may cause harm in some long-stay patients.

PMID- 25855904
TI  - Individualizing treatment to optimize survival outcomes in breast cancer: case
      discussion.

PMID- 25855902
TI  - Toll-like receptor 9 signaling regulates tissue factor and tissue factor pathway
      inhibitor expression in human endothelial cells and coagulation in mice.
AB  - OBJECTIVE: Bacterial DNA (CpG DNA) persists in tissues and blood under
      pathological conditions that are associated with enhanced intravascular
      coagulation. Toll-like receptor 9 recognizes CpG DNA and elicits innate and
      adoptive immunity, yet the impact of CpG DNA on coagulation has not been studied.
      In this study, we investigated the effects of CpG DNA on the expression and
      activity of tissue factor, a key initiator of coagulation and tissue factor
      pathway inhibitor in human coronary artery endothelial cells and on coagulation
      in mice. DESIGN: Controlled in vitro and in vivo studies. SETTING: University
      research laboratory. SUBJECTS: Cultured human coronary artery endothelial cell,
      wild-type mice, and TLR9-deficient mice. INTERVENTIONS: Human coronary artery
      endothelial cell was challenged with CpG DNA, and tissue factor and tissue factor
      pathway inhibitor expression and activity were assessed. In mice, the effects of
      CpG DNA on bleeding time and plasma levels of thrombin-antithrombin complexes and
      tissue factor were measured. MEASUREMENTS AND MAIN RESULTS: We found that CpG
      DNA, but not eukaryotic DNA, evoked marked nuclear factor-kappaB-mediated
      increases in tissue factor expression at both messenger RNA and protein levels,
      as well as in tissue factor activity. Conversely, CpG DNA significantly reduced
      tissue factor pathway inhibitor transcription, secretion, and activity.
      Inhibition of Toll-like receptor 9 with a telomere-derived Toll-like receptor 9
      inhibitory oligonucleotide or transient Toll-like receptor 9 knockdown with small
      interfering RNA attenuated human coronary artery endothelial cell responses to
      CpG DNA. In wild-type mice, CpG DNA shortened the bleeding time parallel with
      dramatic increases in plasma thrombin-antithrombin complex and tissue factor
      levels. Pretreatment with inhibitory oligonucleotide or anti-tissue factor
      antibody or genetic deletion of TLR9 prevented these changes, whereas depleting
      monocytes with clodronate resulted in a modest partial inhibition. CONCLUSIONS:
      Our findings demonstrate that bacterial DNA through Toll-like receptor 9 shifted
      the balance of tissue factor and tissue factor pathway inhibitor toward
      procoagulant phenotype in human coronary artery endothelial cells and activated
      blood coagulation in mice. Our study identifies Toll-like receptor 9 inhibitory
      oligonucleotides as potential therapeutic agents for the prevention of
      coagulation in pathologies where bacterial DNA may abundantly be present.

PMID- 25855903
TI  - Individualizing treatment to optimize survival outcomes in breast cancer.

PMID- 25855905
TI  - Lower-limb performance disparities: implications for exercise prescription in
      multiple sclerosis.
AB  - The purpose of this study was to examine unilateral lower-limb exercise tolerance
      during fixed-load cycling to quantify performance disparities of the legs. Eight
      individuals with relapsing-remitting multiple sclerosis (MS) and seven controls
      performed submaximal single-leg cycling. Individuals with MS performed
      significantly more work with the stronger leg than the weaker leg (stronger leg:
      6.4 +/- 1.7 kJ, weaker leg: 4.7 +/- 2.5 kJ, p = 0.02). The control group
      displayed no statistical differences between limbs (p = 0.36). These results
      highlight a need for individualized exercise testing when prescribing training
      programs for those with MS. 

PMID- 25855906
TI  - Primary intestinal follicular lymphoma in a patient with very vague abdominal
      symptoms.

PMID- 25855907
TI  - Endoscopic treatment of a cystic duct stump leak complicated by aberrant bile
      duct communication.

PMID- 25855908
TI  - Metallic stent placement for malignant biliary stenosis through pancreatic duct
      in pancreaticobiliary maljunction.

PMID- 25855910
TI  - Fibrinogenopenia caused by tigecycline: a case report.

PMID- 25855909
TI  - Bulky end-capped [1]benzothieno[3,2-b]benzothiophenes: reaching high-mobility
      organic semiconductors by fine tuning of the crystalline solid-state order.
AB  - A series of bulky end-capped [1]benzothieno[3,2-b]benzothiophenes (BTBTs) are
      developed in order to tune the packing structure via terminal substitution. A
      coupled theoretical and experimental study allows us to identify 2,7-di-tert
      butylBTBT as a new high-performance organic semiconductor with large and well
      balanced transfer integrals, as evidenced by quantum-chemical calculations.
      Single-crystal field-effect transistors show a remarkable average saturation
      mobility of 7.1 cm(2) V(-1) s(-1) . 

PMID- 25855911
TI  - The Aquamantis(r) system as alternative for parenchimal divison and hemostasis in
      liver resection for hepatocellular carcinoma: a preliminary study.

PMID- 25855912
TI  - Alternative anestesia method in reduction of tibiofibular joint dislocation:
      regional block.

PMID- 25855913
TI  - An improved method of supercharged transposed latissimus dorsi flap with the skin
      paddle for the management of a complicated lumbosacral defect.
AB  - OBJECTIVE: Treatment of non-healing wounds of lower back often poses a powerful
      challenge. We present one of the first report of treatment of a lumbosacral
      defect with a supercharged latissimus dorsi flap with the skin paddle. CASE
      REPORT: We report a case of a 59 year-old man with myeloma of the sacral spine
      who underwent radiotherapy and chemotherapy and subsequently, laminectomies and
      placement of hardware for ongoing paresis and spine instability. Then, he
      developed an open wound and osteomyelitis of the spine with culture positive
      tuberculous granulomas. After multiple surgical debridement, he presented to our
      service and was treated with a single stage debridement followed by the
      performance of a latissimus dorsi musculocutaneous flap based on paraspinal
      perforators and supercharged. RESULTS: This solution, allowed for augmentation of
      blood flow to the muscle with the inferior gluteal artery, provided coverage of
      the defect resistant to the pressure, and simplified post-operative management of
      the patient. CONCLUSIONS: Alternative treatment options, including free tissue
      transfer, posed difficulties in finding suitable recipient vessels near the
      defect, in inserting the flap so as to restore its original length without
      compromising blood flow, and in postoperative care of the patient. Treatment of a
      lumbosacral defect with a supercharged latissimus dorsi flap with the skin paddle
      may represent a milestone procedure for complicated lower spine wounds.

PMID- 25855914
TI  - Comparison between PRP, PRGF and PRF: lights and shadows in three similar but
      different protocols.
AB  - OBJECTIVE: The main goal of the modern surgery is to get a low invasiveness and a
      high rate of clinical healing: in the last years, it has been introduced the
      concept of a "regenerative surgery", and many techniques has been widely
      described in the literature. The most used are PRP, PRGF and PRF techniques. Aim
      of this research is to compare the three protocol of PRP, PRF and PRGF in their
      essential features, so to suggest to the practitioners the best blood product to
      use in the regenerative surgery. DISCUSSION AND CONCLUSIONS: Among the advantages
      that shows the PRF, compared to PRP and PRGF, we can cite a greater simplicity of
      production for the absence of manipulation that leads to a reduced possibility of
      alteration of the protocol due to an error of the operator. The special texture
      of the PRF and its biological features shows clearly an interesting surgical
      versatility and all the characteristics that can support a faster tissues
      regeneration and high-quality clinical outcomes.

PMID- 25855915
TI  - Primary intraosseous ganglioneuromatous paraganglioma of the sacrum with
      immunopositivity for cytokeratin.
AB  - BACKGROUND: Paragangliomas are derived from neurosecretory cells believed to be
      of neural crest origin. A spinal location of paraganglioma is rare and usually
      presents as an intradural mass. PATIENT AND METHODS: A primary intraosseous
      paraganglioma of sacrum is extremely unusual, and only 6 cases were reported. In
      this study, we report a rare case of a 44-year-old man with the complaint of low
      back pain and lower extremity weakness. Imaging workup, including computerized
      tomography (CT), and magnetic resonance imaging (MRI) presented an intraosseous
      sacral lesion with invasion of sacrum in the S1-S3 vertebrae, and extension to L4
      L5 spinal canal. The patient underwent subtotal tumor resection, followed by
      radiation therapy. RESULTS: The morphological and immunohistochemical studies
      revealed a composite tumor of paraganglioma and ganglioneuroma components, with
      immunopositivity for cytokeratin. CONCLUSIONS: To the best of our knowledge, this
      is the first report in the literature demonstrating an intraosseous sacral
      paraganglioma with these 2 pathological features.

PMID- 25855916
TI  - Evaluation of effectiveness of hydrocolloid dressing vs ceramide containing
      dressing against pressure ulcers.
AB  - OBJECTIVE: Pressure Ulcers (PUs) often is an indication of quality of nursing
      care as it remains as severe manifestation of the integrity of impaired skin. Our
      study designed to evaluate the effectiveness of hydrocolloid dressings and
      ceramide dressings in healing of PU. PATIENTS AND METHODS: The study was done at
      Chinese hospital between Feb 2014-November 2014. 72 study group patients and 25
      control group patients were included in the study. The study group patients were
      divided into Group A with 24 patients received only ordinary hydrocolloid
      dressings, Group B with 24 patients who ceramide containing hydrocolloid
      dressings and Group C with 24 patients received both hydrocolloid and ceramide
      dressings. Dressings were applied for 4 weeks. The dressings were changed every
      10 days and skin conditions such as pH of the skin, hydration are measured by
      capacitive method. RESULTS: Among 72 study population 48 (66.7%) were male and 24
      (33.3%) were females. Group A with 18 (75%) males and 6 (25%) females, group B
      with 20 (83.3%) males and 4 (16.7%) females, and group C with 10 (41.7%) males
      and 14 (58.3%) females. 25 Control group patients with 8 (32%) males and 16 (68%)
      females. Erythema seen in 4/24 (16.67%) group A patients, group B and C patients
      had 1/24 (4.17%) erythema. In control group patients 6/25(24%) developed
      erythema. CONCLUSIONS: In our study, we evaluated the effectiveness of the
      hydrocolloid dressings and ceramide containing dressings in which ceramide
      containing dressings showed effective prevention and water holding capacity. Our
      study highlights that ceramide containing dressings found to be more effective in
      reducing erythema and improving the healing of PU.

PMID- 25855917
TI  - Can we modulate asthma maintenance treatment level with disease seasonal
      variations?
AB  - Asthma can have clinical seasonal fluctuations due to different exposure factors.
      The analysis of our data and literature confirm a seasonal trend of asthma
      severity. In this brief review, authors discuss the possibility to adapt
      maintenance therapy level to clinical seasonal fluctuations, by increasing
      treatment in some seasons to prevent exacerbations and by decreasing it in
      others, when symptoms are low, in order to minimize costs and maximize safety.
      Literature and our data (concerning studies carried out in areas with a temperate
      climate) indicate that asthma severity is reduced in summer while it tends to
      increase in the other seasons. Authors conclude that a preventive increasing
      maintenance treatment level during the season when we know that patients worsen
      (starting some weeks before symptom worsening) may reduce asthma exacerbation
      risks. On the contrary, a summer treatment reduction, in patients that improve
      during this period, may be considered only in asthma phenotypes with a benign
      disease course in time. 

PMID- 25855918
TI  - Effect of three different doses of arginine enhanced enteral nutrition on
      nutritional status and outcomes in well nourished postsurgical cancer patients: a
      randomized single blinded prospective trial.
AB  - OBJECTIVE: Patients with head and neck cancer undergoing surgery have a high
      occurrence of postoperative complications. The aim of our study was to
      investigate whether postoperative nutrition of head and neck cancer patients,
      using an enhanced enteral formula with three different doses of arginine could
      improve nutritional variables as well as clinical outcome, depending of arginine
      dose. PATIENTS AND METHODS: A population of 84 patients with oral and laryngeal
      cancer was enrolled. At surgery patients were randomly assigned to three
      different treatment groups, each one containing at less 28 patients. Group I (28
      patients) received an enteral diet supplements with a low physiological dose of
      arginine (5.7 g per day), group II (28 patients) received an isocaloric,
      isonitrogenous enteral formula with a medium dose of arginine (12.3 g per day)
      and group III (28 patients) received an isocaloric, isonitrogenous enteral
      formula with a high dose of arginine (18.9 g per day). RESULTS: The length of
      postoperative stay had a trend to be better with high dose of arginine received
      (31.9 +/- 17.2 days in group I vs 27.8 +/- 15.2 days in group II vs 24.8 +/- 18.3
      days in group III: p = 0.034). No differences were detected in postoperative
      infections complications and diarrhea. Fistula was less frequent in groups II and
      III than I (10.7% group I vs 3.6% group II vs 3.6% group III: p = 0.033), The
      length of postoperative stay had a trend to be better with high dose of arginine
      received (31.9 +/- 17.2 days in group I vs 27.8 +/- 15.2 days in group II vs 24.8
      +/- 18.3 days in group III: p = 0.034). CONCLUSIONS: Our results suggest that
      these patients could benefit from a high dose of arginine enhanced enteral
      formula to decrease length of hospital stay and fistula wound complications.

PMID- 25855919
TI  - Is an elevated neutrophil-to-lymphocyte ratio a predictor of metabolic syndrome
      in patients with chronic obstructive pulmonary disease?
AB  - OBJECTIVE: This study aimed to evaluate the diagnostic value of the neutrophil-to
      lymphocyte ratio (NLR) in early detection of metabolic syndrome (MetS) in
      patients with chronic obstructive pulmonary disease (COPD). PATIENTS AND METHODS:
      We retrospectively enrolled hospital records of 140 COPD patients and 50 sex and
      age-matched healthy controls. The diagnostic values of NLR were estimated using
      the sensitivity, specificity, and area under the receiver operating
      characteristic curve (AUC). RESULTS: In total, 140 patients with COPD of which 63
      patients had MetS and 50 healthy subjects were included in the study. We found
      that the NLR values of the stable COPD patients were significantly higher than
      those of the controls (p < 0.001). Among patients with COPD, the NLR was
      significantly higher in patients with than without MetS (p < 0.001). The AUC of
      the NLR was 0.898 in patients with MetS. The optimal NLR cut-off was 2.56 and was
      validated in the testing set. For evaluation of MetS, the sensitivity and
      specificity were 84.1% and 84.4% in patients with COPD under the suggested cut
      offs. CONCLUSIONS: The NLR is a simple, effective, and practical predictor of
      MetS in patients with stable COPD. It has potential value in public health
      practice for management of patients with COPD.

PMID- 25855920
TI  - Effects of pioglitazone and glipizide on platelet function in patients with type
      2 diabetes.
AB  - OBJECTIVE: Platelet hyper-reactivity is one of the most important causes of
      accelerated atherosclerosis and increased risk of thrombotic vascular events
      associated with type 2 diabetes mellitus (T2DM). This study aimed to investigate
      the effects of different add-on anti-diabetic therapies on platelet function in
      T2DM patients. PATIENTS AND METHODS: A three-group parallel study was conducted
      in 120 patients with T2DM (HbA1c > 7%) undergoing treatment with metformin.
      Patients were randomly assigned to receive add-on therapy with glipizide or
      pioglitazone. Markers of PF (platelet PAC-1 binding, p-selectin expression and
      adenosine diphosphate-induced platelet aggregation) were measured at weeks 0, 4
      and 24. Primary outcome was effects of pioglitazone and glipizide on platelet
      aggregation. Secondary outcome was the related influencing factors of platelet
      aggregation. RESULTS: There were no significant differences in baseline
      characteristics between glipizide and pioglitazone groups. After 24 weeks,
      fasting blood glucose (p < 0.01) and HbA1c (p < 0.01) were higher in pioglitazone
      group than those in glipizide group. Fasting insulin (p < 0.01) and HOMA-IR (p <
      0.01) were lower in pioglitazone group than that in glipizide group. Markers of
      platelet function were significantly decreased in both groups at 24 weeks (PAC-1:
      pioglitazone: -63.3%; glipizide: -45.9%; p-selectin: pioglitazone: -73.9%;
      glipizide: -54.9%; platelet aggregation: pioglitazone: -24.1%; glipizide: -13.4%;
      all p < 0.01 vs. baseline), but the decrease in platelet function was more
      significant in pioglitazone group (p < 0.05). Multiple linear regression analyses
      showed that platelet aggregation was independently associated with treatment
      groups (p < 0.001), Triglyceride (p = 0.009) and HDL-C (p = 0.015). CONCLUSIONS:
      Add-on therapy with pioglitazone may be more effective than glipizide for
      inhibiting platelet activation in T2DM.

PMID- 25855921
TI  - Primary aldosteronism with concurrent primary hyperparathyroidism: clinical case
      load in a single centre.
AB  - OBJECTIVE: Primary aldosteronism (PA) represents the main cause of endocrine
      secondary arterial hypertension in which aldosterone production is
      inappropriately elevated. Primary hyperparathyroidism (PHPT) is an endocrine
      disease characterized by hypercalcemia due to overproduction of parathyroid
      hormone (PTH). Although these two endocrine pathologies are secondary to
      hypertension in middle aged population, the occurrence of the PHPT in PA patients
      has rarely reported in the literature. The aim of the study was to describe some
      PA patients with concurrent PHPT, referred in a tertiary center of arterial
      hypertension. PATIENTS: We performed a retrospective study. In particular, the
      registry of 306 patients with PA seen in our center since 2004 was examined and
      revealed 8 patients (2.6%) with concurrent PHPT. CONCLUSIONS: There are several
      possible explanations for the association of these two endocrine disorders,
      including the combination was a random finding that PA inheres PHPT or vice
      versa.

PMID- 25855922
TI  - Thyroid dysfunction and thyroid autoimmunity in euthyroid women in achieving
      fertility.
AB  - OBJECTIVE: Thyroid disease is the second most common endocrine condition in women
      of childbearing age. Thyroid hormones are involved in control of menstrual cycle
      and in achieving fertility affecting the actions of follicle-stimulating hormone
      and luteinizing hormone on steroid biosynthesis by specific triiodothyronine
      sites on oocytes; therefore, affect all aspects of reproduction. It remains
      controversial if pregnant women should be screened for thyroid dysfunction.
      Purpose of this review was to examine recent studies on the assessment of thyroid
      dysfunction in pregnancy, its treatment and newly perspective of thyroid
      autoimmunity in pregnant euthyroid women in achieving fertility. METHODS: An
      electronic search was conducted using the internet medical databases:
      Medline/PubMed, EMBASE, EBSCO, and the Cochrane library. RESULTS: Thyroid gland
      faces great challenge in pregnancy when many hormonal changes occur. Precondition
      for normal follicular development and ovulation is pulsate gonadothropin
      realizing hormone secretion. Thyroid dysfunction in pregnancy is classified as
      forms of hypothyroidism (positivity of thyroid autoantibody, isolated
      hypothyroidism, and subclinical or overt hypothyroidism), hyperthyroidism, and
      autoimmune disease, but also thyroid nodules and cancer, iodine insufficiency and
      postpartum thyroiditis. These conditions can cause adverse effects on mother and
      fetus including pregnancy loss, gestational hypertension, or pre-eclampsia, pre
      term delivery, low birth weight, placental abruption and postpartum hemorrhage.
      There is an evidence that thyroid autoimmunity, in thyroid dysfunction adversely
      affects conception and pregnancy outcomes, but it is unclear what impact has
      isolated eumetabolic thyroid autoimmunity in achieving fertility, especially in
      women undergoing in vitro fertilization. Treatment of euthyroid pregnant women
      with positive thyroid peroxides antibodies is still controverse, but not few
      studies show that levothyroxine substitution is able to lower the chance of
      miscarriage and premature delivery. CONCLUSIONS: Further randomized trials are
      needed to expand our knowledge of physiologic changes in thyroid function during
      the pregnancy and to reveal mechanisms by which thyroid autoimmunity in euthyroid
      women affect fertility, especially the success of assisted reproductive
      technology in achieving the same and validity of levothyroxine administration in
      thyroid autoimmunity positive women.

PMID- 25855923
TI  - Niacin-respondent subset of schizophrenia - a therapeutic review.
AB  - It is well known that niacin deficiency manifests with several psychiatric
      manifestations. Also historically evidence has accumulated that niacin
      augmentation can be used for treatment of schizophrenia. However, the
      etiopathological associations between niacin deficiency and schizophrenia as well
      as the mechanism of action of niacin in its treatment. More importantly, the
      subgroups of schizophrenia which will respond to niacin augmentation has never
      been highlighted in the literature. In this article, we review three of the
      mechanisms in which niacin deficiency could lead to schizophrenic symptoms: (1)
      Niacin deficiency neurodegeneration (2) Membrane phospholipid deficiency
      hypothesis and (3) Adrenochrome hypothesis. We will further move towards the
      clinical as well as treatment related associations as reviewed from the
      literature. Here, we propose a model that a subset of schizophrenia can respond
      to niacin augmentation therapy better than other subsets because these patients
      have contributions in their psychotic manifestations from the neural degeneration
      resulting from niacin deficiency. We present a short description of our case
      report which showed rapid improvement in schizophrenic psychotic symptoms
      subsequent to administration of niacin as an augmentation therapy. We, thus,
      propose that niacin deficiency is a contributory factor in schizophrenia
      development in some patients and symptom alleviation in these patients will
      benefit from niacin augmentation, especially in some particular psychotic
      features. 

PMID- 25855924
TI  - Isolated brain stem edema in a pediatric patient with head trauma: a case report.
AB  - Brain stem is the most vital part of our body and is a transitional region of the
      brain that connects the cerebrum with the spinal cord. Though, being small in
      size, it is full of indispensible functions such as the breathing, heart beat.
      Injury to the brain stem has similar effects as a brain injury, but it is more
      fatal. Use of the Glasgow Coma Score as a prognostic indicator of outcome in
      patients with head injuries is widely accepted in clinical practice. Traumatic
      brain stem edema in children is rare, but is associated with poor outcome. The
      question is that whether it is being aware of computerized tomography appearance
      of the posterior fossa when initial evaluating pediatric patients with head
      trauma at emergency clinics. Normal and edematous brain stem without an
      additional pathology are slightly different and not distinguished easily. On the
      other hand, brain stem edema should be promptly identified and appropriately
      treated in a short time. 

PMID- 25855925
TI  - Analysis on the correlation factors for hemorrhagic transformation after
      intravenous thrombolytic therapy.
AB  - OBJECTIVE: To examine the correlation factors for hemorrhagic transformation
      after intravenous thrombolytic therapy, so as to improve the forecast about
      hemorrhagic transformation in the process of thrombolysis, and provide
      theoretical basis for prognosis of the patients. PATIENTS AND METHODS: A total of
      1223 patients with intravenous thrombolytic therapy including NIHSS score before
      intravenous thrombolytic therapy and MRS score by follow-up of three months after
      intravenous thrombolytic therapy were enrolled in this study, and related
      clinical data were collected. t test, chi2 test and logistic regression analysis
      were used to find the correlation factors for hemorrhagic transformation.
      RESULTS: Single-factor analysis found hypertension, diabetes mellitus, history of
      stroke and collateral circulation insufficiency had statistical significances
      between each type of hemorrhage group groups. Amongst of the history of
      hypertension, diabetes and stroke was correlation factor for prognosis.
      CONCLUSIONS: Intravenous thrombolysis hemorrhagic transformation associated with
      these factors including the vessel wall, blood composition and biochemical
      markers.

PMID- 25855926
TI  - Study on the effect of urinary kallidinogenase after thrombolytic treatment for
      acute cerebral infarction.
AB  - OBJECTIVE: To evaluate the safety and efficacy of urinary kallidinogenase for
      recombinant tissue-type plasminogen activator (rt-PA) intravenous thrombolytic
      treatment in patients with acute cerebral infarction. PATIENTS AND METHODS: All
      200 patients with acute cerebral infarction were randomized 1:1 into an
      experimental group (100 cases) and a control group (100 cases). Patients in the
      control group were administrated rt-PA (0/9 mg/kg) while patients in the
      experimental group were given urinary kallidinogenase by intravenous drip (0.15
      PNAU/d, for 7 days) after rt-PA intravenous thrombolytic treatment (0.9 mg/kg).
      The main evaluation index was NIHSS and BI. RESULTS: Compared to the control
      group, the NIHSS scores were significantly lower 7 and 90 days after thrombolytic
      therapy (t = 2.391, 2.714; p < 0.05). BI scores were obviously higher at 90 days
      after thrombolytic therapy in the experimental group (t = 2.675, p < 0.05).
      CONCLUSIONS: Urinary kallidinogenase may improve the treatment effect for rt-PA
      intravenous thrombolytic treatment in patients with acute cerebral infraction.

PMID- 25855927
TI  - Decreased CUL4B expression inhibits malignant proliferation of glioma in vitro
      and in vivo.
AB  - OBJECTIVE: Cullin 4B (CUL4B) is a component of the Cullin 4B-Ring E3 ligase
      complex (CRL4B) that plays a role in proteolysis and is implicated in
      tumorigenesis. However, little is known about CUL4B function in human brain
      tumors, including glioma. MATERIALS AND METHODS: Here, to investigate the
      involvement of CUL4B in glioma tumorigenesis, endogenous CUL4B expression was
      depleted in glioblastoma cell lines U87 and U251 by RNA interference (RNAi).
      RESULTS: Knockdown of CUL4B via shRNA-delivering lentiviruses significantly
      decreased cell proliferation and colony formation, causing G1 phase cell cycle
      arrest in both cell lines via down-regulation of cyclin D1 and up-regulation of
      p16. While increasing the expression of the tumor suppressor PTEN, CUL4B
      knockdown alleviated in vivo tumorigenesis in glioma xenograft nude mice and
      impeded cell migration via suppression of MMP-9. CONCLUSIONS: Therefore,
      knockdown of CUL4B is likely to provide a novel alternative for targeted therapy
      of glioma deserving further investigation.

PMID- 25855928
TI  - Water extract of brewers' rice induces antiproliferation of human colorectal
      cancer (HT-29) cell lines via the induction of apoptosis.
AB  - OBJECTIVE: Brewers' rice, a mixture of broken rice, rice bran, and rice germ, is
      a rice by-product in the rice industry. The present study was designed to
      investigate the in vitro cytotoxicity of the water extract of brewers' rice (WBR)
      against colorectal cancer (HT-29) cells. MATERIALS AND METHODS: The cytotoxicity
      activity was determined using the lactate dehydrogenase (LDH) assay. The
      morphological changes of the HT-29 cells were observed using inverted light and
      fluorescence microscope. Cell cycle and apoptotic cell death analyses were
      performed using flow cytometer. Besides that, the selected polyphenolic compounds
      in WBR were also analyzed using ultra performance liquid chromatography (UPLC).
      RESULTS: The cytotoxicity results showed that WBR was more cytotoxic (but not
      significantly different) in HT-29 cells compared to the MBR, with IC50 value of
      21.88 +/- 12.43 ug/mL and 34.50 +/- 5.92 ug/mL for WBR and MBR, respectively (p >
      0.05). WBR-treated HT-29 cells displayed the typical characteristics of
      apoptosis, as visualized using inverted light and fluorescence microscope. WBR
      also significantly increased the number of early and late apoptotic HT-29 cells
      compared to control cells (p < 0.05). Results from UPLC analysis demonstrated
      that ferulic acid (36.42 +/- 2.97 ug/g) was found the highest level in WBR,
      followed by gallic acid (26.09 +/- 2.01 ug/g) and p-coumaric acid (7.13 +/- 0.36
      ug/g). These phenolics are speculated to partially contribute to apoptotic cell
      death. CONCLUSIONS: Our results suggested that WBR derived from natural sources
      might represent a potential chemopreventive agent against colon cancer.

PMID- 25855929
TI  - RLN2 regulates in vitro invasion and viability of osteosarcoma MG-63 cells via
      S100A4/MMP-9 signal.
AB  - OBJECTIVE: Relaxin-2 (RLN2) increases cell migration, invasiveness and
      proliferation in vitro of osteosarcoma cells, but the molecular mechanisms of
      this action are still unknown. In the present study, we identified S100A4 /MMP-9
      signaling as a major mediator of the actions of RLN2 in osteosarcoma cells in
      vitro. MATERIALS AND METHODS: We have established stable transfectants of
      osteosarcoma MG-63 cells using small interfering RNA (siRNA) targeting RLN2. The
      stable transfectants (MG-63/RLN2 siRNA cells) were treated with 20 mM BB94 (a
      kind of MMP-9 activator) or 100 mM recombinant Human RLN2 (B-29/A-24) for 24 hs
      or transfected with S100A4 cDNA plasmid for 48 hrs or MMP-9 siRNA for 48 hrs then
      treated 100 mM recombinant Human RLN2 (B-29/A-24). Western blot assay was used to
      detect RLN2, S100A4 and MMP-9 expression. Matrigel invasion assay and wound
      healing assay was used to detect invasion in vitro. MTT was used to detect cell
      viability. RESULTS: Knockdown of RLN2 using small interfering RNA decreases
      S100A4 and MMP-9 expression and inhibits invasion and cell viability in vitro. in
      MG-63 cells. Treatment with 100 mM recombinant Human RLN2 (B-29/A-24) for 24 hrs
      in MG-63/ RLN2 siRNA cells increases S100A4 and MMP-9 expression, and increases
      the invasion and cell viability in vitro in MG-63 cells. Transfection with S100A4
      cDNA plasmid in MG-63/RLN2 siRNA cells for 48 hrs increases MMP-9 expression, and
      increase the invasion and cell viability of MG-63/RLN2 siRNA cells. Treatment
      with 20 mM BB94 (MMP-9 activator) for 24 hrs in MG-63/RLN2 siRNA cells increases
      MMP-9 expression, and increases the invasion and cell viability in vitro. in MG
      63 cells. CONCLUSIONS: Our results indicate that RLN2 regulats cell migration,
      invasiveness and proliferation of osteosarcoma cells in vitro, which may be
      mediated through S100A4/MMP-9 signaling.

PMID- 25855930
TI  - The mechanism and inhibitory effect of recombinant human P53 adenovirus injection
      combined with paclitaxel on human cervical cancer cell HeLa.
AB  - OBJECTIVE: To investigate the effect of recombinant human p53 adenovirus
      injection combined with paclitaxel on human cervical cancer HeLa cell
      proliferation, apoptosis and expression of vascular endothelial growth factor
      (VEGF). MATERIALS AND METHODS: Detection of effects of paclitaxel, rAd-p53, and
      drug combination on the proliferation of HeLa cells by MTT method. Detection of
      effects of paclitaxel, rAd-p53, and drug combination on the proliferation of HeLa
      cells by diamidino-phenyl-indole (DAPI) staining. Detection of effects of
      paclitaxel, rAd-p53, and drug combination on the expression of VEGF of HeLa cells
      by Western blotting. RESULTS: Paclitaxel, rAd-p53 alone or in combination could
      inhibit the proliferation of HeLa cells in 24-72 h. The inhibition is time
      dependent and dose dependent. Inhibition of HeLa cells in the combination group
      was significantly higher than single use of paclitaxel group and rAd-P53 group (p
      < 0.05). The combined effect of the coefficient of drug interaction (CDI) value
      was CDI < 1, showing that the two have a synergistic effect. Cell inhibition rate
      combined group of RAd-P53 (5 * l07 vp/mL) and paclitaxel (3 ug/mL) 48 h after
      application is higher than that of monotherapy group [(54.0 +/- 0.92) % vs. (31.8
      +/- 0.58) %, (27.2 +/- 0.55) %, p < 0.05]. The apoptosis rate of HeLa cells in
      combination group was significantly higher than that in paclitaxel group, rAd-p53
      alone group [(83 +/- 0.07) % vs. (11 +/- 0.01) %, (36 +/- 0.04) %, (62 +/- 0.05)
      %, p < 0.05]. Expression of VEGF in HeLa cells of combination group was
      significantly lower than that of the two single drug groups. Expression of VEGF
      in HeLa cells was decreased by (81 + 0.08) %, (45 + 0.07) % and (60 + 0.06) % (p
      < 0.05), respectively. CONCLUSIONS: The effect of rAd-p53 and paclitaxel
      inhibiting HeLa cell proliferation and induction of apoptosis is better than the
      single drug. Its mechanism may be related to the down-regulation of VEGF.

PMID- 25855931
TI  - Time course effect of hypoxia on bone marrow-derived endothelial progenitor cells
      and their effects on left ventricular function after transplanted into acute
      myocardial ischemia rat.
AB  - OBJECTIVE: Ischemic heart disease is the most common cause of cardiovascular
      morbidity and mortality in the industrialized world, and the incidence has been
      increasing in developing countries. Stem cell transplantation has emerged as a
      potent new therapeutic strategy for acute/chronic ischemic heart disease and has
      been explored extensively. The present study aimed to investigate whether hypoxic
      preconditioning of endothelial progenitor cells (EPCs) before transplantation
      could ameliorate their survival and engraftment in ischemic tissue and the
      potential mechanisms. MATERIALS AND METHODS: EPCs extracted were subjected to
      increasing hypoxia for 24-72 h, survival and function of the preconditioned EPCs
      were assayed in both in vitro and in vivo. RESULTS: Hypoxia for 24 h caused
      significant enhancements in formation of tube like structure and motility of BM
      EPCs (p < 0.05), as well as mRNA expressions of CXCR4, PI3K, AKT, and NF-kappaB,
      while these effects were reversed by prolonged hypoxia (48 and 72 h, p < 0.05).
      Hypoxia of BM-EPCs for 24 h did not result in increased apoptosis resistance, and
      cell apoptosis was even enhanced by prolonged hypoxia. In vivo transplantation
      experiments demonstrated the beneficial effect of hypoxic EPCs on left
      ventricular (LV) functions after acute myocardial ischemia (AMI). CONCLUSIONS:
      Shorter-term hypoxia showed better survival, differentiation and function of BM
      EPCs in vivo, further study was still needed to optimize the hypoxic pattern of
      BM-EPCs so as to better protect heart from myocardial ischemic injury. The
      present study showed evidence suggested that hypoxic preconditioning did exert
      further beneficial effects of BM-EPCs on preservation of LV function after AMI.
      Short-term exposure to hypoxia for about 24 h provided better condition for
      survival and function of BM-EPCs.

PMID- 25855932
TI  - ATRA and As2O3 regulate differentiation of human hematopoietic stem cells into
      granulocyte progenitor via alteration of HoxB8 expression.
AB  - OBJECTIVE: This study aimed to investigate the effect of all-trans retinoic acid
      (ATRA) and/or arsenic trioxide (As2O3) on homeobox B8 (HOXB8) mRNA and protein
      expressions during the differentiation and proliferation of hematopoietic stem
      cells (HSCs) to colony forming unit-granulocyte (CFU-G) in order to explore the
      pathogenesis of leukemia mediated by HOXB8 at mRNA and protein level. MATERIALS
      AND METHODS: Twelve cord blood samples were collected from the fetal placenta
      umbilical vein and cultured in vitro. The proliferation and differentiation of
      cord blood HSCs into CFU-G was continuously disrupted with 10 nmol/l of ATRA
      and/or 10 nmol/l of As2O3. The expression of HOXB8 mRNA and protein were detected
      by quantitative real-time polymerase chain reaction (qRT-PCR) and Western-blot,
      respectively. RESULTS: HOXB8 mRNA/protein expression was detected in control,
      ATRA, As2O3 and ATRA +As2O3 groups on days 3, 7, and 12 of culture. HOXB8
      mRNA/protein expression was detectable on day 3, reached its highest level on day
      7 and decreased on day 12. HOXB8 mRNA/protein expression in ATRA, As2O3 and
      ATRA+As2O3 was upregulated compared with control group (p < 0.05). CONCLUSIONS:
      There is a positive relationship between HOXB8 gene expression and granulocyte
      progenitor hematopoiesis. ATRA/As2O3 up-regulate the expression of HOXB8
      mRNA/protein, and treatment of leukemia with ATRA/As2O3 may regulate HOX gene
      expression.

PMID- 25855933
TI  - A novel approach for differentiating etiology of gallstone formation:
      sistocholedochal angle.
AB  - OBJECTIVE: Many etiological factors such as glad bladder motility disorders,
      chemical component of bile and chemical content of bile have been accepted on
      gallstone formation; but anatomic variations of bile duct has been never
      discussed before. The aim of this study was to assess whether the anatomical
      measurements of cystic canal length, common bile duct length, choledoc length and
      the angle between the cystic duct and common bile duct junction (sistocholedochal
      angle: SCA) affects the gallstone formation. PATIENTS AND METHODS: MRI data of
      patients who had undergone magnetic resonance cholecysto pancreatography (MRCP)
      due to any reason, were collected retrospectively. A total of 126 patients was
      divided into two groups as without (group I; n=38) and with (group II; n=88)
      gallstone formation. The cystic canal, choledoc and common bile duct length and
      SCA measurements were obtained. RESULTS: There was no significant difference
      between two groups on the means of cystic canal, choledoc and common bile duct
      lengths (p > 0.05) but SCA measurements were significantly higher in group II
      compared with group I, statistically (p < 0.05); showing that as the SCA
      increases, the incidence of gallstone formation increases. CONCLUSIONS: Higher
      SCA values can be indictable on gallstone formation.

PMID- 25855934
TI  - The therapeutic management of gut barrier leaking: the emerging role for mucosal
      barrier protectors.
AB  - OBJECTIVE: Gut barrier is a functional unit organized as a multi-layer system and
      its multiple functions are crucial for maintaining gut homeostasis. Numerous
      scientific evidences showed a significant association between gut barrier leaking
      and gastro-intestinal/extra-intestinal diseases. MATERIALS AND METHODS: In this
      review we focus on the relationship between gut barrier leaking and human health.
      At the same time we speculate on the possible new role of gut barrier protectors
      in enhancing and restoring gut barrier physiology with the final goal of
      promoting gut health. RESULTS: The alteration of the equilibrium in gut barrier
      leads to the passage of the luminal contents to the underlying tissues and thus
      into the bloodstream, resulting in the activation of the immune response and in
      the induction of gut inflammation. This permeability alteration is the basis for
      the pathogenesis of many diseases, including infectious enterocolitis,
      inflammatory bowel diseases, irritable bowel syndrome, small intestinal bacterial
      overgrowth, celiac disease, hepatic fibrosis, food intolerances and also atopic
      manifestations. Many drugs or compounds used in the treatment of gastrointestinal
      disease are able to alter the permeability of the intestinal barrier. Recent data
      highlighted and introduced the possibility of using gelatin tannate, a mucosal
      barrier protector, for an innovative approach in the management of intestinal
      diseases, allowing an original therapeutic orientation with the aim of enhancing
      mucus barrier activity and restoring gut barrier. CONCLUSIONS: These results
      suggest how the mucus layer recovering, beside the gut microbiota modulation,
      exerted by gut barrier protectors could be a useful weapon to re-establish the
      physiological intestinal homeostasis after an acute and chronic injury.

PMID- 25855935
TI  - Gut barrier in health and disease: focus on childhood.
AB  - The gut barrier is a functional unit, organized as a multi-layer system, made up
      of two main components: a physical barrier surface, which prevents bacterial
      adhesion and regulates paracellular diffusion to the host tissues, and a deep
      functional barrier, that is able to discriminate between pathogens and commensal
      microorganisms, organizing the immune tolerance and the immune response to
      pathogens. Other mechanisms, such as gastric juice and pancreatic enzymes (which
      both have antibacterial properties) participate in the luminal integrity of the
      gut barrier. From the outer layer to the inner layer, the physical barrier is
      composed of gut microbiota (that competes with pathogens to gain space and energy
      resources, processes the molecules necessary to mucosal integrity and modulates
      the immunological activity of deep barrier), mucus (which separates the
      intraluminal content from more internal layers and contains antimicrobial
      products and secretory IgA), epithelial cells (which form a physical and
      immunological barrier) and the innate and adaptive immune cells forming the gut
      associated lymphoid tissue (which is responsible for antigen sampling and immune
      responses). Disruption of the gut barrier has been associated with many
      gastrointestinal diseases, but also with extra-intestinal pathological condition,
      such as type 1 diabetes mellitus, allergic diseases or autism spectrum disorders.
      The maintenance of a healthy intestinal barrier is therefore of paramount
      importance in children, for both health and economic reasons. Many drugs or
      compounds used in the treatment of gastrointestinal disorders act through the
      restoration of a normal intestinal permeability. Several studies have highlighted
      the role of probiotics in the modulation and reduction of intestinal
      permeability, considering the strong influence of gut microbiota in the
      modulation of the function and structure of gut barrier, but also on the immune
      response of the host. To date, available weapons for the maintenance and repair
      of gut barrier are however few, even if promising. Considerable efforts,
      including both a better understanding of the gut barrier features and mechanisms
      in health and disease, and the development of new pharmacological approaches for
      the modulation of gut barrier components, are needed for the prevention and
      treatment of gastrointestinal and extraintestinal diseases associated with gut
      barrier impairment. 

PMID- 25855936
TI  - The relationship between T-wave peak-to end interval and ST segment recovery on
      intracoronary ECG during primary PCI.
AB  - OBJECTIVE: T-wave peak to end interval (TPE) is a measure of repolarization
      dispersion, which has been reported as a major arrhythmogenic factor post acute
      myocardial infarction. The aim of our study was to investigate the changes in TPE
      in this patient population with regard to peri-procedural intracoronary ECG
      findings. PATIENTS AND METHODS: Forty-four patients (34 male and mean age of 54.9
      +/- 10.9 years) with acute STEMI were included. Intracoronary ECG was performed
      during primary PCI. TPE indices were calculated before and after the procedure.
      Measurement of the intracoronary ST-segment was carried out before and just after
      coronary blood flow was established in the infarct related artery. Intracoronary
      ST-segment resolution (IC-STR) was defined as >= 1 mm compared to baseline.
      RESULTS: There was no difference with respect to baseline characteristics when
      patients with IC-STR were compared with patients without IC-STR. TPE values
      decreased significantly after primary PCI in patients with IC-STR (80.9 +/- 22.8
      ms vs. 65.8 +/- 14.4 ms; p < 0.001) whereas they did not change significantly
      after PCI in patients without IC-STR (79.2 +/- 20.9 ms vs. 68.5 +/- 16.3 ms; p =
      0.18). CONCLUSIONS: TPE measured from surface ECG recordings is significantly
      reduced in STEMI patients with successful reperfusion after primary PCI, as
      determined by IC-ECG recordings.

PMID- 25855937
TI  - Common genes in coronary artery disease from Europe, Asia and North America
      regardless of race and lifestyle.
AB  - OBJECTIVE: Coronary artery disease (CAD) remains one of the major causes of death
      worldwide. Despite considerable advances in the prevention and treatment of CAD,
      its complications, morbidity and mortality still remain very high, and vary
      widely across different ethnic groups. MATERIALS AND METHODS: To detect genes
      involved in the development of CAD, we collected gene expression studies in the
      blood samples of CAD patients from different continents by searching the Gene
      Expression Omnibus database (GEO), performed a comparative analysis of gene
      expression between CAD patients and normal controls (NC) in each continent and
      identified the common set of differentially expressed genes (DEGs) between CAD
      patients and NC across different continents. PPI networks of the common set of
      DEGs were established by Cytoscape software to understand their biological role
      in CAD. RESULTS: A total of 575, 868 and 476 genes were identified to be
      significantly differentially expressed between CAD patients and NC in Asia,
      Europe and North America. 24 genes were found common in three different
      continents, and 6 genes were previously linked to CAD or atherosclerosis. In the
      PPIs network the significant hub proteins contained IRF4 (Degree = 23), PLAUR
      (Degree = 17) and HIST1H2AE (Degree = 15). CONCLUSIONS: Not only did we detect
      gene expression differences in the blood samples between CAD and NC in Asia,
      Europe and North America population, but analysis of the three population groups
      revealed a common set of 24 genes regardless of differences related to race,
      ethnicity, lifestyle, and environmental factor which may provide key factors to
      understand the pathogenesis of CAD and lead to development of diagnostic markers
      and/or effective therapeutic strategies.

PMID- 25855938
TI  - Efficacy of drug-eluting stent for chronic total coronary occlusions at different
      follow-up duration: a systematic review and meta-analysis.
AB  - OBJECTIVE: DESs have been proved to be beneficial for patients with chronic total
      coronary occlusions (CTO) in terms of cardiac function and other prognosis. We
      aim to compare the efficacy and safety of drug-eluting stent (DES) and bare-metal
      stent (BMS) in CTO recanalization at different follow-up duration. METHODS:
      Articles comparing outcomes between DES and BMS implantation in patients with CTO
      was searched. A fixed-effect (inverse-variance weighted) and random-effect
      (DerSimonian and Laird) model were used to analyze the pooling results. RESULTS:
      A total of 29 comparative studies including 24 cohort studies and 5 randomized
      controlled studies were identified with a total of 9140 patients (5008 received
      BMS and 4132 received DES). The risk of all cause death for DES was higher at 6
      months and lower at 12 months than BMS, and no significant difference was shown
      at 24, 36 and 60 months. DES group had lower risk of MI after 12 months
      implantation, and no difference was shown at 6, 24, 36 and 60 months. Major
      adverse cardiovascular event (MACE)-free survival was clinically and
      significantly improved by 73%, 68%, 49%, 40% and 37% respectively in DES group at
      6,12, 24, 36, and 60 months. CONCLUSIONS: DES is superior to BMS in binary
      restenosis, reocclusion and MACE-free survival during long-term follow up. The
      occurrences of all-cause death and MI show that the risk rate of BMS is higher
      than that of DES at 12 months. The frequency of all-cause death of DES is higher
      than BMS at 6 months. DES has higher risk of in-stent thrombosis than BMS at 36
      months of implantation.

PMID- 25855941
TI  - The impact of chemotherapy-induced nausea and vomiting.

PMID- 25855940
TI  - Poly(3,4-ethylenedioxythiophene) nanoparticle and poly(E-caprolactone)
      electrospun scaffold characterization for skeletal muscle regeneration.
AB  - Injuries to peripheral nerves and/or skeletal muscle can cause scar tissue
      formation and loss of function. The focus of this article is the creation of a
      conductive, biocompatible scaffold with appropriate mechanical properties to
      regenerate skeletal muscle. Poly(3,4-ethylenedioxythiophene) (PEDOT)
      nanoparticles (Np) were electrospun with poly(E-caprolactone) (PCL) to form
      conductive scaffolds. During electrospinning, ribboning, larger fiber diameters,
      and unaligned scaffolds were observed with increasing PEDOT amounts. To address
      this, PEDOT Np were sonicated prior to electrospinning, which resulted in
      decreased conductivity and increased mechanical properties. Multi-walled carbon
      nanotubes (MWCNT) were added to the 1:2 solution in an effort to increase
      conductivity. However, the addition of MWCNT had little effect on scaffold
      conductivity, and the elastic modulus and yield stress of the scaffold increased
      as a result. Rat muscle cells attached and were active on the 1-10, 1-2, 3-4, and
      1-1 PCL-PEDOT scaffolds; however, the 3-4 scaffolds had the lowest level of
      metabolic activity. Although the scaffolds were cytocompatible, further
      development of the fabrication method is necessary to produce more highly aligned
      scaffolds capable of promoting skeletal muscle cell alignment and eventual
      regeneration.

PMID- 25855939
TI  - Extreme Precipitation and Emergency Room Visits for Gastrointestinal Illness in
      Areas with and without Combined Sewer Systems: An Analysis of Massachusetts Data,
      2003-2007.
AB  - BACKGROUND: Combined sewer overflows (CSOs) occur in combined sewer systems when
      sewage and stormwater runoff are released into water bodies, potentially
      contaminating water sources. CSOs are often caused by heavy precipitation and are
      expected to increase with increasing extreme precipitation associated with
      climate change. OBJECTIVES: The aim of this study was to assess whether the
      association between heavy rainfall and rate of emergency room (ER) visits for
      gastrointestinal (GI) illness differed in the presence of CSOs. METHODS: For the
      study period 2003-2007, time series of daily rate of ER visits for GI illness and
      meteorological data were organized for three exposure regions: a) CSOs impacting
      drinking water sources, b) CSOs impacting recreational waters, c) no CSOs. A
      distributed lag Poisson regression assessed cumulative effects for an 8-day lag
      period following heavy (>= 90th and >= 95th percentile) and extreme (>= 99th
      percentile) precipitation events, controlling for temperature and long-term time
      trends. RESULTS: The association between extreme rainfall and rate of ER visits
      for GI illness differed among regions. Only the region with drinking water
      exposed to CSOs demonstrated a significant increased cumulative risk for rate
      (CRR) of ER visits for GI for all ages in the 8-day period following extreme
      rainfall: CRR: 1.13 (95% CI: 1.00, 1.28) compared with no rainfall. CONCLUSIONS:
      The rate of ER visits for GI illness was associated with extreme precipitation in
      the area with CSO discharges to a drinking water source. Our findings suggest an
      increased risk for GI illness among consumers whose drinking water source may be
      impacted by CSOs after extreme precipitation. CITATION: Jagai JS, Li Q, Wang S,
      Messier KP, Wade TJ, Hilborn ED. 2015. Extreme precipitation and emergency room
      visits for gastrointestinal illness in areas with and without combined sewer
      systems: an analysis of Massachusetts data, 2003-2007. Environ Health Perspect
      123:873-879; http://dx.doi.org/10.1289/ehp.1408971.

PMID- 25855943
TI  - Management of chemotherapy-induced nausea and vomiting in clinical practice.

PMID- 25855944
TI  - New data in emerging treatment options for chemotherapy-induced nausea and
      vomiting in clinical practice: general discussion.

PMID- 25855942
TI  - Clinical trial data in chemotherapy-induced nausea and vomiting.

PMID- 25855945
TI  - Sub-ms dynamics of the instability onset of electrospinning.
AB  - Electrospun polymer jets are imaged for the first time at an ultra-high rate of
      10,000 frames per second, investigating the process dynamics, and the instability
      propagation velocity and displacement in space. The polymer concentration,
      applied voltage bias and needle-collector distance are systematically varied, and
      their influence on the instability propagation velocity and on the jet angular
      fluctuations is analyzed. This allows us to unveil the instability formation and
      cycling behavior, and its exponential growth at the onset, exhibiting radial
      growth rates of the order of 10(3) s(-1). Allowing the conformation and evolution
      of polymeric solutions to be studied in depth, high-speed imaging at the sub-ms
      scale shows significant potential for improving the fundamental knowledge of
      electrified jets, leading to finely controllable bending and solution stretching
      in electrospinning, and consequently better designed nanofiber morphologies and
      structures.

PMID- 25855946
TI  - Ebola Virus Disease: Ethics and Emergency Medical Response Policy.
AB  - Caring for patients affected with Ebola virus disease (EVD) while simultaneously
      preventing EVD transmission represents a central ethical challenge of the EVD
      epidemic. To address this challenge, we propose a model policy for resuscitation
      and emergent procedure policy of patients with EVD and set forth ethical
      principles that lend support to this policy. The policy and principles we propose
      bear relevance beyond the EVD epidemic, offering guidance for the care of
      patients with other highly contagious, virulent, and lethal diseases. The policy
      establishes (1) a limited code status for patients with confirmed or suspected
      EVD. Limited code status means that a code blue will not be called for patients
      with confirmed or suspected EVD at any stage of the disease; however, properly
      protected providers (those already in full protective equipment) may initiate
      resuscitative efforts if, in their clinical assessment, these efforts are likely
      to benefit the patient. The policy also requires that (2) resuscitation not be
      attempted for patients with advanced EVD, as resuscitation would be medically
      futile; (3) providers caring for or having contact with patients with confirmed
      or suspected EVD be properly protected and trained; (4) the treating team
      identify and treat in advance likely causes of cardiac and respiratory arrest to
      minimize the need for emergency response; (5) patients with EVD and their proxies
      be involved in care discussions; and (6) care team and provider discretion guide
      the care of patients with EVD. We discuss ethical issues involving medical
      futility and the duty to avoid harm and propose a utilitarian-based principle of
      triage to address resource scarcity in the emergency setting. 

PMID- 25855947
TI  - Carbon nanotube catalysts: recent advances in synthesis, characterization and
      applications.
AB  - Carbon nanotubes are promising materials for various applications. In recent
      years, progress in manufacturing and functionalizing carbon nanotubes has been
      made to achieve the control of bulk and surface properties including the
      wettability, acid-base properties, adsorption, electric conductivity and
      capacitance. In order to gain the optimal benefit of carbon nanotubes,
      comprehensive understanding on manufacturing and functionalizing carbon nanotubes
      ought to be systematically developed. This review summarizes methodologies of
      manufacturing carbon nanotubes via arc discharge, laser ablation and chemical
      vapor deposition and functionalizing carbon nanotubes through surface oxidation
      and activation, doping of heteroatoms, halogenation, sulfonation, grafting,
      polymer coating, noncovalent functionalization and nanoparticle attachment. The
      characterization techniques detecting the bulk nature and surface properties as
      well as the effects of various functionalization approaches on modifying the
      surface properties for specific applications in catalysis including heterogeneous
      catalysis, photocatalysis, photoelectrocatalysis and electrocatalysis are
      highlighted. 

PMID- 25855953
TI  - Carbohydrate-derived amphiphilic macromolecules: a biophysical structural
      characterization and analysis of binding behaviors to model membranes.
AB  - The design and synthesis of enhanced membrane-intercalating biomaterials for drug
      delivery or vascular membrane targeting is currently challenged by the lack of
      screening and prediction tools. The present work demonstrates the generation of a
      Quantitative Structural Activity Relationship model (QSAR) to make a priori
      predictions. Amphiphilic macromolecules (AMs) "stealth lipids" built on aldaric
      and uronic acids frameworks attached to poly(ethylene glycol) (PEG) polymer tails
      were developed to form self-assembling micelles. In the present study, a defined
      set of novel AM structures were investigated in terms of their binding to lipid
      membrane bilayers using Quartz Crystal Microbalance with Dissipation (QCM-D)
      experiments coupled with computational coarse-grained molecular dynamics (CG MD)
      and all-atom MD (AA MD) simulations. The CG MD simulations capture the insertion
      dynamics of the AM lipophilic backbones into the lipid bilayer with the PEGylated
      tail directed into bulk water. QCM-D measurements with Voigt viscoelastic model
      analysis enabled the quantitation of the mass gain and rate of interaction
      between the AM and the lipid bilayer surface. Thus, this study yielded insights
      about variations in the functional activity of AM materials with minute
      compositional or stereochemical differences based on membrane binding, which has
      translational potential for transplanting these materials in vivo. More broadly,
      it demonstrates an integrated computational-experimental approach, which can
      offer a promising strategy for the in silico design and screening of therapeutic
      candidate materials. 

PMID- 25855954
TI  - Transmembrane-4-L-six-family-1, a potential predictor for poor prognosis,
      overexpressed in human glioma.
AB  - Transmembrane-4-L-six-family-1 (TM4SF1), a tumor-associated antigen, is expressed
      in various human epithelial malignancies including breast, ovarian, lung, and
      colon carcinomas. The aim of the present study was to measure TM4SF1 gene
      expression in human glioma tissues and to investigate its relationship with
      patient outcome. We measured TM4SF1 expression in tumor tissue from 72 patients
      with glioma and in eight control brain tissues by means of quantitative reverse
      transcription-PCR, western blotting, and immunohistochemistry. The survival data
      including age, sex, Karnofsky performance scores, epilepsy, size of tumor, extent
      of resection, pathological grade, and TM4SF1 expression were analyzed using
      Kaplan-Meier analysis and the multivariate test method (Cox's proportional
      hazards model). We observed a higher level of TM4SF1 expression in human glioma
      tissues than in control brain tissues. Furthermore, TM4SF1 expression increased
      with ascending tumor grade (rs=0.950, P<0.05). Kaplan-Meier analysis with the log
      rank test indicated that high TM4SF1 expression had a significant negative impact
      on overall survival (P<0.001). Moreover, multivariate Cox regression analysis
      revealed that TM4SF1 was an independent prognostic marker in glioma patients.
      These findings indicate that (a) TM4SF1 is overexpressed in human gliomas in
      general and (b) the precise level of expression might predict outcome and could
      be of clinical value. 

PMID- 25855955
TI  - One-hour proteome analysis in yeast.
AB  - Recent advances in chromatography and mass spectrometry (MS) have made rapid and
      deep proteomic profiling possible. To maximize the performance of the recently
      produced Orbitrap hybrid mass spectrometer, we have developed a protocol that
      combines improved sample preparation (including optimized cellular lysis by
      extensive bead beating) and chromatographic conditions (specifically, 30-cm
      capillary columns packed with 1.7-MUm bridged ethylene hybrid material) and the
      manufacture of a column heater (to accommodate flow rates of 350-375 nl/min) that
      increases the number of proteins identified across a single liquid chromatography
      tandem MS (LC-MS/MS) separation, thereby reducing the need for extensive sample
      fractionation. This strategy allowed the identification of up to 4,002 proteins
      (at a 1% false discovery rate (FDR)) in yeast (Saccharomyces cerevisiae strain
      BY4741) over 70 min of LC-MS/MS analysis. Quintuplicate analysis of technical
      replicates reveals 83% overlap at the protein level, thus demonstrating the
      reproducibility of this procedure. This protocol, which includes cell lysis,
      overnight tryptic digestion, sample analysis and database searching, takes ~24 h
      to complete. Aspects of this protocol, including chromatographic separation and
      instrument parameters, can be adapted for the optimal analysis of other
      organisms. 

PMID- 25855956
TI  - Transcriptome-wide identification of adenosine-to-inosine editing using the ICE
      seq method.
AB  - Inosine (I), a modified base found in the double-stranded regions of RNA in
      metazoans, has various roles in biological processes by modulating gene
      expression. Inosine is generated from adenosine (A) catalyzed by ADAR (adenosine
      deaminase acting on RNA) enzymes in a process called A-to-I RNA editing. As
      inosine is converted to guanosine (G) by reverse transcription, the editing sites
      can be identified by simply comparing cDNA sequences with the corresponding
      genomic sequence. One approach to screening I sites is by deep sequencing based
      on A-to-G conversion from genomic sequence to cDNA; however, this approach
      produces a high rate of false positives because it cannot efficiently eliminate G
      signals arising from inevitable mapping errors. To address this issue, we
      developed a biochemical method to identify inosines called inosine chemical
      erasing (ICE), which is based on cyanoethylation combined with reverse
      transcription. ICE was subsequently combined with deep sequencing (ICE-seq) for
      the reliable identification of transcriptome-wide A-to-I editing sites. Here we
      describe a protocol for the practical application of ICE-seq, which can be
      completed within 22 d, and which allows the accurate identification of
      transcriptome-wide A-to-I RNA editing sites. 

PMID- 25855958
TI  - Effectiveness of the risk of malignancy index and the risk of ovarian malignancy
      algorithm in a cohort of women with ovarian cancer: does histotype and stage
      matter?
AB  - OBJECTIVE: To examine the performance of the Risk of Malignancy Index (RMI) and
      Risk of Ovarian Malignancy Algorithm (ROMA) by histologic subtype and stage of
      disease in a cohort of women with ovarian cancer. METHODS: All patients with
      confirmed ovarian cancer at the Princess Margaret Hospital between February 2011
      and January 2013 were eligible for study inclusion. Preoperative cancer antigen
      125, human epididymis protein 4, and ultrasound findings were reviewed, and the
      sensitivity and false-negative rates of the RMI and ROMA were determined by stage
      of disease and tumor histology. RESULTS: A total of 131 patients with ovarian
      cancer were identified. High-grade serous (HGS) histology was most frequently
      associated with stage III/IV disease (n = 46 [72% of stage III/IV]) vs stage I (n
      = 5 [11% of stage I]; P < 0.0001). Clear cell (CC) and endometrioid (EC)
      histology presented most commonly with stage I disease (n = 9 [20%] and n = 13
      [29% of stage I cases], respectively). Median cancer antigen 125 and human
      epididymis protein 4 values were significantly higher for HGS than for EC or CC
      histology. Risk of Malignancy Index II demonstrated the highest sensitivity of
      the 3 RMI algorithms. All RMIs and ROMA were significantly more sensitive in
      predicting malignancy in patients with HGS than EC or CC histology. Risk of
      Malignancy Index II (n = 38) and ROMA (n = 35) exhibited sensitivities of 68% and
      54% and false-negative rates of 32% and 46%, respectively, for patients with
      stage I disease vs sensitivities of 94% and 93% and false-negative rates of 6%
      and 7% for patients with stage III/IV disease. CONCLUSION: Both RMI and ROMA
      performed well for the detection of advanced ovarian cancer and HGS histology.
      These triaging algorithms do not perform well in patients with stage I disease
      where EC and CC histologies predominate. Clinicians should be cautious using RMI
      or ROMA scoring tools to triage isolated adnexal masses because many patients
      with stage I malignancies would be missed.

PMID- 25855959
TI  - Corrigendum.

PMID- 25855957
TI  - The FTMap family of web servers for determining and characterizing ligand-binding
      hot spots of proteins.
AB  - FTMap is a computational mapping server that identifies binding hot spots of
      macromolecules-i.e., regions of the surface with major contributions to the
      ligand-binding free energy. To use FTMap, users submit a protein, DNA or RNA
      structure in PDB (Protein Data Bank) format. FTMap samples billions of positions
      of small organic molecules used as probes, and it scores the probe poses using a
      detailed energy expression. Regions that bind clusters of multiple probe types
      identify the binding hot spots in good agreement with experimental data. FTMap
      serves as the basis for other servers, namely FTSite, which is used to predict
      ligand-binding sites, FTFlex, which is used to account for side chain
      flexibility, FTMap/param, used to parameterize additional probes and FTDyn, for
      mapping ensembles of protein structures. Applications include determining the
      druggability of proteins, identifying ligand moieties that are most important for
      binding, finding the most bound-like conformation in ensembles of unliganded
      protein structures and providing input for fragment-based drug design. FTMap is
      more accurate than classical mapping methods such as GRID and MCSS, and it is
      much faster than the more-recent approaches to protein mapping based on mixed
      molecular dynamics. By using 16 probe molecules, the FTMap server finds the hot
      spots of an average-size protein in <1 h. As FTFlex performs mapping for all low
      energy conformers of side chains in the binding site, its completion time is
      proportionately longer. 

PMID- 25855960
TI  - Histone acetyltransferase PCAF accelerates apoptosis by repressing a
      GLI1/BCL2/BAX axis in hepatocellular carcinoma.
AB  - P300/CBP-associated factor (PCAF), a histone acetyltransferase (HAT), has been
      found to regulate numerous cell signaling pathways controlling cell fate by
      acetylating both histone and non-histone proteins. We previously reported that
      PCAF upregulates cell apoptosis by inactivating Serine/Threonine Protein Kinase 1
      (AKT1) signaling and consequently inhibits hepatocellular carcinoma (HCC) cell
      growth. Here, we show that PCAF can directly acetylate cytoplasmic GLI1 protein
      at lysine 518, preventing its nuclear translocation and promoter occupancy, and
      consequently suppressing Hedgehog (Hh) signaling in HCC. Further, our results
      show that GLI1 can increase Bcl-2 expression and downregulate BAX. Interestingly,
      forced expression of PCAF reduced Bcl-2 expression, upregulated BAX and repressed
      cell apoptosis. Further, we provide evidence that knockdown of GLI1 abrogates the
      inhibitory effect of PCAF on the growth of HCC in vitro. PCAF was also found to
      sensitize HCC cells to 5-fluorouracil (5-FU) treatment by regulating GLI1/Bcl
      2/BAX axis-dependent apoptosis. In vivo experiments also confirmed the regulatory
      effect of PCAF on the GLI1/Bcl-2/BAX axis and its synergistic antitumor effects
      with 5-FU. Gene expression microarray studies showed that PCAF was downregulated
      in HCC tissues compared with adjacent liver tissues and that PCAF expression was
      significantly associated with longer overall survival and recurrence-free
      survival after surgery. Together, these results show that PCAF can induce cell
      apoptosis by modulating a GLI1/Bcl-2/BAX axis that in turn suppresses HCC
      progression, and suggest that 5-FU may exert a stronger anti-tumor effect in
      patients with PCAF expression in HCC tumors. 

PMID- 25855961
TI  - The canonical Wg signaling modulates Bsk-mediated cell death in Drosophila.
AB  - Cell death is an essential regulatory mechanism for removing unneeded cells in
      animal development and tissue homeostasis. The c-Jun N-terminal kinase (JNK)
      pathway has pivotal roles in the regulation of cell death in response to various
      intrinsic and extrinsic stress signals. The canonical Wingless (Wg) signaling has
      been implicated in cell proliferation and cell fate decisions, whereas its role
      in cell death remains largely elusive. Here, we report that activated Bsk (the
      Drosophila JNK homolog) induced cell death is mediated by the canonical Wg
      signaling. First, loss of Wg signaling abrogates Bsk-mediated caspase-independent
      cell death. Second, activation of Wg signaling promotes cell death in a caspase
      independent manner. Third, activation of Bsk signaling results in upregulated
      transcription of wingless (wg) gene. Finally, Wg pathway participates in the
      physiological function of Bsk signaling in development. These findings not only
      reveal a previously undiscovered role of Wg signaling in Bsk-mediated cell death,
      but also provide a novel mechanism for the interplay between the two important
      signaling pathways in development. 

PMID- 25855962
TI  - Oroxylin A inhibits glycolysis-dependent proliferation of human breast cancer via
      promoting SIRT3-mediated SOD2 transcription and HIF1alpha destabilization.
AB  - Alterations of cellular metabolism play a central role in the development and
      progression of cancer. Oroxylin A, an active flavonoid of a Chinese traditional
      medicinal plant, was previously shown to modulate glycolysis in cancer cells.
      However, the mechanism by which oroxylin A regulates glycolysis is still not well
      defined. Here, we show that oroxylin A inhibits glycolysis in breast cancer cells
      via the Sirtuin 3 (SIRT3)-mediated destabilization of hypoxia-inducible factor
      1alpha (HIF1alpha), which controls glycolytic gene expression. Oroxylin A
      promotes superoxide dismutase (SOD2) gene expression through SIRT3-regulated DNA
      binding activity of FOXO3a and increases the activity of SOD2 by promoting SIRT3
      mediated deacetylation. In vivo, oroxylin A inhibits the growth of transplanted
      human breast tumors associated with glycolytic suppression. These data indicate
      that oroxylin A inhibits glycolysis-dependent proliferation of breast cancer
      cells, through the suppression of HIF1alpha stabilization via SIRT3 activation,
      providing preclinical information for the cancer therapies of SIRT3 stimulation. 

PMID- 25855963
TI  - Peroxisome proliferator-activated receptorbeta/delta activation is essential for
      modulating p-Foxo1/Foxo1 status in functional insulin-positive cell
      differentiation.
AB  - Peroxisome proliferator-activated receptors (PPARs) participate in energy
      homeostasis and play essential roles in diabetes therapy through their effects on
      non-pancreas tissues. Pathological microenvironment may influence the metabolic
      requirements for the maintenance of stem cell differentiation. Accordingly,
      understanding the mechanisms of PPARs on pancreatic beta-cell differentiation may
      be helpful to find the underlying targets of disrupted energy homeostasis under
      the pancreatic disease condition. PPARs are involved in stem cell differentiation
      via mitochondrial oxidative phosphorylation, but the subtype member activation
      and the downstream regulation in functional insulin-positive (INS+) cell
      differentiation remain unclear. Here, we show a novel role of PPARbeta/delta
      activation in determining INS+ cell differentiation and functional maturation. We
      found PPARbeta/delta expression selectively upregulated in mouse embryonic
      pancreases or stem cells-derived INS+ cells at the pancreatic mature stage in
      vivo and in vitro. Strikingly, given the inefficiency of generating INS+ cells in
      vitro, PPARbeta/delta activation displayed increasing mouse and human ES cell
      derived INS+ cell numbers and insulin secretion. This phenomenon was closely
      associated with the forkhead box protein O1 (Foxo1) nuclear shuttling, which was
      dependent on PPARbeta/delta downstream PI3K/Akt signaling transduction. The
      present study reveals the essential role of PPARbeta/delta activation on p
      Foxo1/Foxo1 status, and in turn, determining INS+ cell generation and insulin
      secretion via affecting pancreatic and duodenal homeobox-1 expression. The
      results demonstrate the underlying mechanism by which PPARbeta/delta activation
      promotes functional INS+ cell differentiation. It also provides potential targets
      for anti-diabetes drug discovery and hopeful clinical applications in human cell
      therapy.

PMID- 25855964
TI  - PHRF1 promotes genome integrity by modulating non-homologous end-joining.
AB  - Methylated histone readers are critical for chromatin dynamics, transcription,
      and DNA repair. Human PHRF1 contains a plant homeodomain (PHD) that recognizes
      methylated histones and a RING domain, which ubiquitinates substrates. A recent
      study reveals that PHRF1 is a tumor suppressor that promotes TGF-beta cytostatic
      signaling through TGIF ubiquitination. Also, PHRF1 is a putative phosphorylation
      substrate of ataxia telangiectasia-mutated/ataxia telangiectasia and Rad3-related
      kinases; however, the role of PHRF1 in DNA damage response is unclear. Here we
      report a novel function of PHRF1 in modulating non-homologous end-joining (NHEJ).
      PHRF1 quickly localizes to DNA damage lesions upon genotoxic insults. Ablation of
      PHRF1 decreases the efficiency of plasmid-based end-joining, whereas PHRF1
      overexpression leads to an elevated NHEJ in H1299 reporter cells.
      Immunoprecipitation and peptide pull-down assays verify that PHRF1 constitutively
      binds to di- and trimethylated histone H3 lysine 36 (H3K36) (H3K36me2 and
      H3K36me3) via its PHD domain. Substitution of S915DT917E to ADAE in PHRF1
      decreases its affinity for NBS1. Both PHD domain and SDTE motif are required for
      its NHEJ-promoting activity. Furthermore, PHRF1 mediates PARP1 polyubiquitination
      for proteasomal degradation. These results suggest that PHRF1 may combine with
      H3K36 methylation and NBS1 to promote NHEJ and stabilize genomic integrity upon
      DNA damage insults.

PMID- 25855965
TI  - Lysosomal ceramide generated by acid sphingomyelinase triggers cytosolic
      cathepsin B-mediated degradation of X-linked inhibitor of apoptosis protein in
      natural killer/T lymphoma cell apoptosis.
AB  - We previously reported that IL-2 deprivation induced acid sphingomyelinase
      mediated (ASM-mediated) ceramide elevation and apoptosis in an NK/T lymphoma cell
      line KHYG-1. However, the molecular mechanism of ASM-ceramide-mediated apoptosis
      during IL-2 deprivation is poorly understood. Here, we showed that IL-2
      deprivation induces caspase-dependent apoptosis characterized by
      phosphatidylserine externalization, caspase-8, -9, and -3 cleavage, and
      degradation of X-linked inhibitor of apoptosis protein (XIAP). IL-2 re
      supplementation rescued apoptosis via inhibition of XIAP degradation without
      affecting caspase cleavage. However, IL-2 deprivation induced ceramide elevation
      via ASM in lysosomes and activated lysosomal cathepsin B (CTSB) but not cathepsin
      D. A CTSB inhibitor CA-074 Me and knockdown of CTSB inhibited ceramide-mediated
      XIAP degradation and apoptosis. Inhibition of ceramide accumulation in lysosomes
      using an ASM inhibitor, desipramine, decreased cytosolic activation of CTSB by
      inhibiting its transfer into cytosol from the lysosome. Knockdown of ASM also
      inhibited XIAP degradation and apoptosis. Furthermore, cell permeable N-acetyl
      sphingosine (C2-ceramide), which increases mainly endogenous d18:1/16:0 and
      d18:1/24:1 ceramide-like IL-2 deprivation, induced caspase-dependent apoptosis
      with XIAP degradation through CTSB. These findings suggest that lysosomal
      ceramide produced by ASM mediates XIAP degradation by activation of cytosolic
      CTSB and caspase-dependent apoptosis. The ASM-ceramide-CTSB signaling axis is a
      novel pathway of ceramide-mediated apoptosis in IL-2-deprived NK/T lymphoma
      cells. 

PMID- 25855966
TI  - Aberrant MEK5/ERK5 signalling contributes to human colon cancer progression via
      NF-kappaB activation.
AB  - This study was designed to evaluate MEK5 and ERK5 expression in colon cancer
      progression and to ascertain the relevance of MEK5/ERK5 signalling in colon
      cancer. Expression of MEK5 and ERK5 was evaluated in 323 human colon cancer
      samples. To evaluate the role of MEK5/ERK5 signalling in colon cancer, we
      developed a stable cell line model with differential MEK5/ERK5 activation. Impact
      of differential MEK5/ERK5 signalling was evaluated on cell cycle progression by
      flow cytometry and cell migration was evaluated by wound healing and transwell
      migration assays. Finally, we used an orthotopic xenograft mouse model of colon
      cancer to assess tumour growth and progression. Our results demonstrated that
      MEK5 and ERK5 are overexpressed in human adenomas (P<0.01) and adenocarcinomas
      (P<0.05), where increased ERK5 expression correlated with the acquisition of more
      invasive and metastatic potential (P<0.05). Interestingly, we observed a
      significant correlation between ERK5 expression and NF-kappaB activation in human
      adenocarcinomas (P<0.001). We also showed that ERK5 overactivation significantly
      accelerated cell cycle progression (P<0.05) and increased cell migration
      (P<0.01). Furthermore, cells with overactivated ERK5 displayed increased NF
      kappaB nuclear translocation and transcriptional activity (P<0.05), together with
      increased expression of the mesenchymal marker vimentin (P<0.05). We further
      demonstrated that increased NF-kappaB activation was associated with increased
      IkappaB phosphorylation and degradation (P<0.05). Finally, in the mouse model,
      lymph node metastasis was exclusively seen in orthotopically implanted tumours
      with overactivated MEK5/ERK5, and not in tumours with inhibited MEK5/ERK5. Our
      results suggested that MEK5/ERK5/NF-kappaB signalling pathway is important for
      tumour onset, progression and metastasis, possibly representing a novel relevant
      therapeutic target in colon cancer treatment. 

PMID- 25855967
TI  - Evaluation of 111in-labelled exendin-4 derivatives containing different meprin
      beta-specific cleavable linkers.
AB  - BACKGROUND: Cleavable linkers, which are specifically cleaved by defined
      conditions or enzymes, are powerful tools that can be used for various purposes.
      Amongst other things, they have been successfully used to deliver toxic payloads
      as prodrugs into target tissues. In this work novel linker sequences targeting
      meprin beta, a metalloprotease expressed in the kidney brush-border membrane,
      were designed and included in the sequence of three radiolabelled exendin-4
      derivatives. As radiolabelled exendin-4 derivatives strongly accumulate in the
      kidneys, we hypothesised that specific cleavage of the radiolabelled moiety at
      the kidney brush-border membrane would allow easier excretion of the activity
      into the urine and therefore improve the pharmacological properties of the
      peptide. RESULTS: The insertion of a cleavable linker did not negatively
      influence the in vitro properties of the peptides. They showed a good affinity to
      the GLP-1 receptor expressed in CHL cells, a high internalisation and
      sufficiently high stability in fresh human blood plasma. In vitro digestion with
      recombinant meprin beta rapidly metabolised the corresponding linker sequences.
      After 60 min the majority of the corresponding peptides were digested and at the
      same time the anticipated fragments were formed. The peptides were also quickly
      metabolised in CD1 nu/nu mouse kidney homogenates. Immunofluorescence staining of
      meprin beta in kidney sections confirmed the expression of the protease in the
      kidney brush-border membrane. Biodistribution in GLP-1 receptor positive tumour
      xenograft bearing mice revealed high specific uptake of the 111In-labelled
      tracers in receptor positive tissue. Accumulation in the kidneys, however, was
      still high and comparable to the lead compound 111In-Ex4NOD40. CONCLUSION: In
      conclusion, we show that the concept of cleavable linkers specific for meprin
      beta is feasible, as the peptides are rapidly cleaved by the enzyme while
      retaining their biological properties.

PMID- 25855968
TI  - Environmental gap analysis to prioritize conservation efforts in eastern Africa.
AB  - Countries in eastern Africa have set aside significant proportions of their land
      for protection. But are these areas representative of the diverse range of
      species and habitats found in the region? And do conservation efforts include
      areas where the state of biodiversity is likely to deteriorate without further
      interventions? Various studies have addressed these questions at global and
      continental scales. However, meaningful conservation decisions are required at
      finer geographical scales. To operate more effectively at the national level,
      finer scale baseline data on species and on higher levels of biological
      organization such as the eco-regions are required, among other factors. Here we
      adopted a recently developed high-resolution potential natural vegetation (PNV)
      map for eastern Africa as a baseline to more effectively identify conservation
      priorities. We examined how well different potential natural vegetations (PNVs)
      are represented in the protected area (PA) network of eastern Africa and used a
      multivariate environmental similarity index to evaluate biases in PA versus PNV
      coverage. We additionally overlaid data of anthropogenic factors that potentially
      influence the natural vegetation to assess the level of threat to different PNVs.
      Our results indicate substantial differences in the conservation status of PNVs.
      In addition, particular PNVs in which biodiversity protection and ecological
      functions are at risk due to human influences are revealed. The data and approach
      presented here provide a step forward in developing more transparent and better
      informed translation from global priorities to regional or national
      implementation in eastern Africa, and are valid for other geographic regions. 

PMID- 25855969
TI  - Quantification of diabetes comorbidity risks across life using nation-wide big
      claims data.
AB  - Despite substantial progress in the study of diabetes, important questions remain
      about its comorbidities and clinical heterogeneity. To explore these issues, we
      develop a framework allowing for the first time to quantify nation-wide risks and
      their age- and sex-dependence for each diabetic comorbidity, and whether the
      association may be consequential or causal, in a sample of almost two million
      patients. This study is equivalent to nearly 40,000 single clinical measurements.
      We confirm the highly controversial relation of increased risk for Parkinson's
      disease in diabetics, using a 10 times larger cohort than previous studies on
      this relation. Detection of type 1 diabetes leads detection of depressions,
      whereas there is a strong comorbidity relation between type 2 diabetes and
      schizophrenia, suggesting similar pathogenic or medication-related mechanisms. We
      find significant sex differences in the progression of, for instance, sleep
      disorders and congestive heart failure in diabetic patients. Hypertension is a
      highly sex-sensitive comorbidity with females being at lower risk during fertile
      age, but at higher risk otherwise. These results may be useful to improve
      screening practices in the general population. Clinical management of diabetes
      must address age- and sex-dependence of multiple comorbid conditions. 

PMID- 25855971
TI  - A systematic review of studies eliciting willingness-to-pay per quality-adjusted
      life year: does it justify CE threshold?
AB  - BACKGROUND: A number of studies have been conducted to estimate willingness to
      pay (WTP) per quality-adjusted life years (QALY) in patients or general
      population for various diseases. However, there has not been any systematic
      review summarizing the relationship between WTP per QALY and cost-effectiveness
      (CE) threshold based on World Health Organization (WHO) recommendation.
      OBJECTIVE: To systematically review willingness-to-pay per quality-adjusted-life
      year (WTP per QALY) literature, to compare WTP per QALY with Cost-effectiveness
      (CE) threshold recommended by WHO, and to determine potential influencing
      factors. METHODS: We searched MEDLINE, EMBASE, Psyinfo, Cumulative Index to
      Nursing and Allied Health Literature (CINAHL), Center of Research Dissemination
      (CRD), and EconLit from inception through 15 July 2014. To be included, studies
      have to estimate WTP per QALY in health-related issues using stated preference
      method. Two investigators independently reviewed each abstract, completed full
      text reviews, and extracted information for included studies. We compared WTP per
      QALY to GDP per capita, analyzed, and summarized potential influencing factors.
      RESULTS: Out of 3,914 articles founded, 14 studies were included. Most studies
      (92.85%) used contingent valuation method, while only one study used discrete
      choice experiments. Sample size varied from 104 to 21,896 persons. The ratio
      between WTP per QALY and GDP per capita varied widely from 0.05 to 5.40,
      depending on scenario outcomes (e.g., whether it extended/saved life or improved
      quality of life), severity of hypothetical scenarios, duration of scenario, and
      source of funding. The average ratio of WTP per QALY and GDP per capita for
      extending life or saving life (2.03) was significantly higher than the average
      for improving quality of life (0.59) with the mean difference of 1.43 (95% CI,
      1.81 to 1.06). CONCLUSION: This systematic review provides an overview summary of
      all studies estimating WTP per QALY studies. The variation of ratio of WTP per
      QALY and GDP per capita depended on several factors may prompt discussions on the
      CE threshold policy. Our research work provides a foundation for defining future
      direction of decision criteria for an evidence-informed decision making system.

PMID- 25855970
TI  - The value of myocardial torsion and aneurysm volume for evaluating cardiac
      function in rabbit with left ventricular aneurysm.
AB  - OBJECTIVE: This study aimed to investigate the effect of left ventricular
      aneurysm (LVA) volume and left ventricular global torsion on cardiac function by
      real time three-dimensional echocardiography (RT-3DE) and two-dimensional speckle
      tracking imaging(2D-STI), to determine the accuracy of RT-3DE and 2D-STI in
      assessing LV function. METHODS: Thirty New Zealand rabbit models of with LVA were
      prepared by ligation of the middle segment of the left anterior descending and
      left circumflex arteries. Four weeks post-procedure, RT-3DE was conducted to
      obtain data on LVEF, left ventricular end-diastolic volume (LVEDV), left
      ventricular end-systolic volume (LVESV), and LVA volume (LVAV), Peak rotation
      angles at the mitral valve annulus level (MV-ROT), peak rotation angles at the
      apical level (AP-ROT), and left ventricular global torsion angles (LV-TOR) were
      measured by 2D-STI. RESULTS: Compared with controls, LVEDV and LVESV were
      significantly increased in the LVA group, while LVEF, MV-ROT, AP-ROT, and LV-TOR
      were consistently reduced (p<0.01). Moreover, LVEF correlated with LVA volume and
      LV torsion angle (r= -0.778 and 0.821, p<0.01). LVA volume/LVEDV had the
      strongest inverse relationship with LVEF (r= -0.911, p<0.01). CONCLUSION: LVA
      volume, LVA volume/LVEDV, and LV torsion may be used as an indicator for
      evaluation of cardiac function after LVA. Moreover, LVA volume/LVEDV may be a
      more sensitive and reliable marker of cardiac function after LVA formation.

PMID- 25855972
TI  - Perioperative chemotherapy in gastroesophageal cancer. A retrospective monocenter
      evaluation of 42 cases.
AB  - BACKGROUND: Perioperative chemotherapy increases the overall and progression-free
      survival of patients suffering from resectable adenocarcinomas of the lower
      esophagus, gastroesophageal junction and stomach (GEC). Comparing different
      chemotherapy regimens platin-based protocols with 5-fluorouracil (5-FU)/calcium
      folinate (CF) or oral fluoropyrimidines were favorable in terms of efficacy and
      side-effects. However, there is no consensus which regimen is the most
      efficacious. METHODS: 42 consecutive patients with resectable GEC (UICC II and
      III) were treated with 3 pre- and postoperative chemotherapy cycles each
      consisting of epirubicin, oxaliplatin and capecitabine (EOX). We analyzed the
      overall survival, progression-free survival and toxicity retrospectively in
      comparison to published data. RESULTS: The median overall survival in our cohort
      was 29 months and the progression-free survival was 17 months. The most frequent
      grade 3 and 4 toxicities during preoperative chemotherapy were diarrhea (16.7%),
      leukocytopenia (9.5%) and nausea (9.5%); overall 38.1% of our patients suffered
      from grade 3 or 4 toxicity. Surgery was carried out in 83% of our patients, 69%
      of those achieved R0 resection. CONCLUSION: Comparing our data with the results
      of previously published randomized trials EOX is at least non-inferior with
      regard to overall survival, progression-free survival and toxicity. In
      conclusion, EOX is an appropriate perioperative therapy for patients with
      resectable GEC.

PMID- 25855973
TI  - Region-oriented and staged treatment strategy in reconstruction of severe
      cervical contracture.
AB  - INTRODUCTION: Severe cervical contracture after burns causes obvious impairment
      of neck movement and the aesthetic silhouette. Although various surgical
      techniques for treatment have been described, there is not a definitive strategy
      to guide treatment. Over the past 6 years, we have been utilizing a region
      oriented and staged treatment strategy to guide reconstruction of severe cervical
      contracture. Satisfactory results have been achieved with this strategy. METHODS:
      The first stage of treatment focuses on the anterior cervical region and
      submental region. Procedures include cicatrix resection, contracture release,
      division and elevation of the platysma to form two platysma flaps, and skin
      grafting. Three to six months later, the second stage treatment is performed,
      which localize to the mental region. This includes scar resection, correction of
      the lower lip eversion, and reconstruction with free (para)scapular skin flap.
      Three subtypes of cervicomental angle that we proposed were measured as
      quantitative tool for evaluation of the reconstruction. RESULTS: 24 patients who
      completed the treatment were reviewed. By the 3rd postoperative month, their CM
      angles changed significantly: the soft tissue CM angle was reduced from 135.0
      degrees  +/- 17.3 degrees  to 111.1 degrees  +/- 11.3 degrees , the osseous CM
      angle increased from 67.1 degrees  +/- 9.0 degrees  to 90.5 degrees  +/- 11.6
      degrees  and the dynamic CM angle increased from 21.9 degrees  +/- 8.7 degrees 
      to 67.4 degrees  +/- 13.1 degrees . 22 in 24 (91.7%) of these patients gained
      notable improvement of cervical motion and aesthetic contour. CONCLUSIONS: Our
      results suggest that the region-oriented and staged treatment strategy can
      achieve satisfactory functional and aesthetic results, combining usage of both
      skin graft and skin flap while minimizing the donor site morbidity.

PMID- 25855974
TI  - High-fat diet-induced insulin resistance does not increase plasma anandamide
      levels or potentiate anandamide insulinotropic effect in isolated canine islets.
AB  - BACKGROUND: Obesity has been associated with elevated plasma anandamide levels.
      In addition, anandamide has been shown to stimulate insulin secretion in vitro,
      suggesting that anandamide might be linked to hyperinsulinemia. OBJECTIVE: To
      determine whether high-fat diet-induced insulin resistance increases anandamide
      levels and potentiates the insulinotropic effect of anandamide in isolated
      pancreatic islets. DESIGN AND METHODS: Dogs were fed a high-fat diet (n = 9) for
      22 weeks. Abdominal fat depot was quantified by MRI. Insulin sensitivity was
      assessed by the euglycemic-hyperinsulinemic clamp. Fasting plasma endocannabinoid
      levels were analyzed by liquid chromatography-mass spectrometry. All metabolic
      assessments were performed before and after fat diet regimen. At the end of the
      study, pancreatic islets were isolated prior to euthanasia to test the in vitro
      effect of anandamide on islet hormones. mRNA expression of cannabinoid receptors
      was determined in intact islets. The findings in vitro were compared with those
      from animals fed a control diet (n = 7). RESULTS: Prolonged fat feeding increased
      abdominal fat content by 81.3+/-21.6% (mean+/-S.E.M, P<0.01). In vivo insulin
      sensitivity decreased by 31.3+/-12.1% (P<0.05), concomitant with a decrease in
      plasma 2-arachidonoyl glycerol (from 39.1+/-5.2 to 15.7+/-2.0 nmol/L) but not
      anandamide, oleoyl ethanolamide, linoleoyl ethanolamide, or palmitoyl
      ethanolamide. In control-diet animals (body weight: 28.8+/-1.0 kg), islets
      incubated with anandamide had a higher basal and glucose-stimulated insulin
      secretion as compared with no treatment. Islets from fat-fed animals (34.5+/-1.3
      kg; P<0.05 versus control) did not exhibit further potentiation of anandamide
      induced insulin secretion as compared with control-diet animals. Glucagon but not
      somatostatin secretion in vitro was also increased in response to anandamide, but
      there was no difference between groups (P = 0.705). No differences in gene
      expression of CB1R or CB2R between groups were found. CONCLUSIONS: In canines,
      high-fat diet-induced insulin resistance does not alter plasma anandamide levels
      or further potentiate the insulinotropic effect of anandamide in vitro.

PMID- 25855975
TI  - Measuring predictability of autonomous network transitions into bursting
      dynamics.
AB  - Understanding spontaneous transitions between dynamical modes in a network is of
      significant importance. These transitions may separate pathological and normal
      functions of the brain. In this paper, we develop a set of measures that, based
      on spatio-temporal features of network activity, predict autonomous network
      transitions from asynchronous to synchronous dynamics under various conditions.
      These metrics quantify spike-timing distributions within a narrow time window as
      a function of the relative location of the active neurons. We applied these
      metrics to investigate the properties of these transitions in excitatory-only and
      excitatory-and-inhibitory networks and elucidate how network topology, noise
      level, and cellular heterogeneity affect both the reliability and the timeliness
      of the predictions. The developed measures can be calculated in real time and
      therefore potentially applied in clinical situations. 

PMID- 25855976
TI  - Recombinant adeno-vaccine expressing enterovirus 71-like particles against hand,
      foot, and mouth disease.
AB  - Enterovirus 71 (EV71) and coxsackieviruses (CV) are the major causative agents of
      hand, foot and mouth disease (HFMD). There is not currently a vaccine available
      against HFMD, even though a newly developed formalin-inactivated EV71 (FI-EV71)
      vaccine has been tested in clinical trial and has shown efficacy against EV71. We
      have designed and genetically engineered a recombinant adenovirus Ad-EVVLP with
      the EV71 P1 and 3CD genes inserted into the E1/E3-deleted adenoviral genome. Ad
      EVVLP were produced in HEK-293A cells. In addition to Ad-EVVLP particles, virus
      like particles (VLPs) formed from the physical association of EV71 capsid
      proteins, VP0, VP1, and VP3 expressed from P1 gene products. They were digested
      by 3CD protease and confirmed to be produced by Ad-EVVLP-producing cells, as
      determined using transmission electron microscopy and western blotting. Mouse
      immunogenicity studies showed that Ad-EVVLP-immunized antisera neutralized the
      EV71 B4 and C2 genotypes. Activation of VLP-specific CD4+ and CD8+/IFN-gamma T
      cells associated with Th1/Th2-balanced IFN-gamma, IL-17, IL-4, and IL-13 was
      induced; in contrast, FI-EV71 induced only Th2-mediated neutralizing antibody
      against EV71 and low VLP-specific CD4+ and CD8+ T cell responses. The antiviral
      immunity against EV71 was clearly demonstrated in mice vaccinated with Ad-EVVLP
      in a hSCARB2 transgenic (hSCARB2-Tg) mouse challenge model. Ad-EVVLP-vaccinated
      mice were 100% protected and demonstrated reduced viral load in both the CNS and
      muscle tissues. Ad-EVVLP successfully induced anti-CVA16 immunities. Although
      antisera had no neutralizing activity against CVA16, the 3C-specific CD4+ and
      CD8+/IFN-gamma T cells were identified, which could mediate protection against
      CVA16 challenge. FI-EV71 did not induce 3C-mediated immunity and had no efficacy
      against the CVA16 challenge. These results suggest that Ad-EVVLP can enhance
      neutralizing antibody and protective cellular immune responses to prevent EV71
      infection and cellular immune responses against CV infection. 

PMID- 25855978
TI  - Genetic diversity of five local Swedish chicken breeds detected by microsatellite
      markers.
AB  - This study aimed at investigating the genetic diversity, relationship and
      population structure of 110 local Swedish chickens derived from five breeds
      (Gotlandshona, Hedemorahona, Olandsk dvarghona, Skansk blommehona, and Bohuslan-
      Dals svarthona, in the rest of the paper the shorter name Svarthona is used)
      using 24 microsatellite markers. In total, one hundred thirteen alleles were
      detected in all populations, with a mean of 4.7 alleles per locus. For the five
      chicken breeds, the observed and expected heterozygosity ranged from 0.225 to
      0.408 and from 0.231 to 0.515, with the lowest scores for the Svarthona and the
      highest scores for the Skansk blommehona breeds, respectively. Similarly, the
      average within breed molecular kinship varied from 0.496 to 0.745, showing high
      coancestry, with Skansk blommehona having the lowest and Svarthona the highest
      coancestry. Furthermore, all breeds showed significant deviations from Hardy
      Weinberg expectations. Across the five breeds, the global heterozygosity deficit
      (FIT) was 0.545, population differentiation index (FST) was 0.440, and the global
      inbreeding of individuals within breed (FIS) was 0.187. The phylogenetic
      relationships of chickens were examined using neighbor-joining trees constructed
      at the level of breeds and individual samples. The neighbor-joining tree
      constructed at breed level revealed two main clusters, with Hedemorahona and
      Olandsk dvarghona breeds in one cluster, and Gotlandshona and Svarthona breeds in
      the second cluster leaving the Skansk blommehona in the middle. Based on the
      results of the STRUCTURE analysis, the most likely number of clustering of the
      five breeds was at K = 4, with Hedemorahona, Gotlandshona and Svarthona breeds
      forming their own distinct clusters, while Olandsk dvarghona and Skansk
      blommehona breeds clustered together. Losses in the overall genetic diversity of
      local Swedish chickens due to breeds extinction varied from -1.46% to -6.723%.
      The results of the current study can be used as baseline genetic information for
      genetic conservation program, for instance, to control inbreeding and to
      implement further genetic studies in local Swedish chickens. 

PMID- 25855977
TI  - Novel epigallocatechin-3-gallate (EGCG) derivative as a new therapeutic strategy
      for reducing neuropathic pain after chronic constriction nerve injury in mice.
AB  - Neuropathic pain is common in peripheral nerve injury and often fails to respond
      to ordinary medication. Here, we investigated whether the two novel
      epigallocatechin-3-gallate (EGCG) polyphenolic derivatives, compound 23 and 30,
      reduce the neuropathic pain in mice chronic constriction nerve injury (CCI).
      First, we performed a dose-response study to evaluate nociceptive sensation after
      administration of EGCG and its derivatives 23 and 30, using the Hargreaves test
      at 7 and 21 days after injury (dpi). We daily administered EGCG, 23 and 30 (10 to
      100 mg/Kg; i.p.) during the first week post-CCI. None of the doses of compound 23
      caused significant pain diminution, whereas 50mg/kg was optimal for both EGCG and
      30 to delay the latency of paw withdrawal. With 50 mg/Kg, we showed that EGCC
      prevented the thermal hyperalgesia from 7 to 21 dpi and compound 30 from 14 to 56
      dpi. To evaluate the molecular mechanisms underpinning why EGCG and compound 30
      differentially prevented the thermal hyperalgesia, we studied several biochemical
      parameters in the dorsal horn of the spinal cord at 14 and 56 dpi. We showed that
      the effect observed with EGCG and compound 30 was related to the inhibition of
      fatty acid synthase (FASN), a known target of these polyphenolic compounds.
      Additionally, we observed that EGCG and compound 30 reduced the expression of CCI
      mediated inflammatory proteins and the nuclear localization of nuclear factor
      kappa B at 14 dpi, but not at 56 dpi. We also strongly detected a decrease of
      synaptic plasma membrane levels of N-methyl-D-asparte receptor 2B in CCI-mice
      treated with compound 30 at 56 dpi. Altogether, compound 30 reduced the chronic
      thermal hyperalgesia induced by CCI better than the natural compound EGCG. Thus,
      our findings provide a rationale for the preclinical development of compound 30
      as an agent to treat neuropathic pain. 

PMID- 25855979
TI  - Orthokeratology to control myopia progression: a meta-analysis.
AB  - OBJECTIVE: To evaluate the clinical treatment effects of orthokeratology to slow
      the progression of myopia. METHODS: Several well-designed controlled studies have
      investigated the effects of orthokeratology in school-aged children. We conducted
      this meta-analysis to better evaluate the existing evidence. Relevant studies
      were identified in the Medline and Embase database without language limitations.
      The main outcomes included axial length and vitreous chamber depth reported as
      the mean +/- standard deviation. The results were pooled and assessed with a
      fixed-effects model analysis. Subgroup analyses were performed according to
      geographical location and study design. RESULTS: Of the seven eligible studies,
      all reported axial length changes after 2 years, while two studies reported
      vitreous chamber depth changes. The pooled estimates indicated that change in
      axial length in the ortho-k group was 0.27 mm (95% confidence interval [CI]:
      0.22, 0.32) less than the control group. Myopic progression was reduced by
      approximately 45%. The combined results revealed that the difference in vitreous
      chamber depth between the two groups was 0.22 mm (95% confidence interval [CI]:
      0.14, 0.31). None of the studies reported severe adverse events. CONCLUSION: The
      overall findings suggest that ortho-k can slow myopia progression in school-aged
      children.

PMID- 25855980
TI  - The EBNA3 family of Epstein-Barr virus nuclear proteins associates with the
      USP46/USP12 deubiquitination complexes to regulate lymphoblastoid cell line
      growth.
AB  - The Epstein-Barr virus (EBV) nuclear proteins EBNA3A, EBNA3B, and EBNA3C interact
      with the cell DNA binding protein RBPJ and regulate cell and viral genes.
      Repression of the CDKN2A tumor suppressor gene products p16(INK4A) and p14(ARF)
      by EBNA3A and EBNA3C is critical for EBV mediated transformation of resting B
      lymphocytes into immortalized lymphoblastoid cell lines (LCLs). To define the
      composition of endogenous EBNA3 protein complexes, we generated lymphoblastoid
      cell lines (LCLs) expressing flag-HA tagged EBNA3A, EBNA3B, or EBNA3C and used
      tandem affinity purification to isolate each EBNA3 complex. Our results
      demonstrated that each EBNA3 protein forms a distinct complex with RBPJ. Mass
      spectrometry revealed that the EBNA3A and EBNA3B complexes also contained the
      deubquitylation complex consisting of WDR48, WDR20, and USP46 (or its paralog
      USP12) and that EBNA3C complexes contained WDR48. Immunoprecipitation confirmed
      that EBNA3A, EBNA3B, and EBNA3C association with the USP46 complex. Using
      chromatin immunoprecipitation, we demonstrate that WDR48 and USP46 are recruited
      to the p14(ARF) promoter in an EBNA3C dependent manner. Mapping studies were
      consistent with WDR48 being the primary mediator of EBNA3 association with the
      DUB complex. By ChIP assay, WDR48 was recruited to the p14(ARF) promoter in an
      EBNA3C dependent manner. Importantly, WDR48 associated with EBNA3A and EBNA3C
      domains that are critical for LCL growth, suggesting a role for USP46/USP12 in
      EBV induced growth transformation.

PMID- 25855981
TI  - Perilipin1 deficiency in whole body or bone marrow-derived cells attenuates
      lesions in atherosclerosis-prone mice.
AB  - AIMS: The objective of this study is to determine the role of perilipin 1 (Plin1)
      in whole body or bone marrow-derived cells on atherogenesis. METHODS AND RESULTS:
      Accumulated evidence have indicated the role of Plin1 in atherosclerosis,
      however, these findings are controversial. In this study, we showed that Plin1
      was assembled and colocalized with CD68 in macrophages in atherosclerotic plaques
      of ApoE-/- mice. We further found 39% reduction of plaque size in the aortic
      roots of Plin1 and ApoE double knockout (Plin1-/-ApoE-/-) females compared with
      ApoE-/- female littermates. In order to verify whether this reduction was
      macrophage-specific, the bone marrow cells from wild-type or Plin1 deficient mice
      (Plin1-/-) were transplanted into LDL receptor deficient mice (LDLR-/-). Mice
      receiving Plin1-/- bone marrow cells showed also 49% reduction in aortic
      atherosclerotic lesions compared with LDLR-/- mice received wild-type bone marrow
      cells. In vitro experiments showed that Plin1-/- macrophages had decreased
      protein expression of CD36 translocase and an enhanced cholesterol ester
      hydrolysis upon aggregated-LDL loading, with unaltered expression of many other
      regulators of cholesterol metabolism, such as cellular lipases, and Plin2 and 3.
      Given the fundamental role of Plin1 in protecting LD lipids from lipase
      hydrolysis, it is reasonably speculated that the assembly of Plin1 in microphages
      might function to reduce lipolysis and hence increase lipid retention in ApoE-/-
      plaques, but this pro-atherosclerotic property would be abrogated on inactivation
      of Plin1. CONCLUSION: Plin1 deficiency in bone marrow-derived cells may be
      responsible for reduced atherosclerotic lesions in the mice.

PMID- 25855982
TI  - Molecular cloning, functional characterization, and evolutionary analysis of
      vitamin D receptors isolated from basal vertebrates.
AB  - The vertebrate genome is a result of two rapid and successive rounds of whole
      genome duplication, referred to as 1R and 2R. Furthermore, teleost fish have
      undergone a third whole genome duplication (3R) specific to their lineage,
      resulting in the retention of multiple gene paralogs. The more recent 3R event in
      teleosts provides a unique opportunity to gain insight into how genes evolve
      through specific evolutionary processes. In this study we compare molecular
      activities of vitamin D receptors (VDR) from basal species that diverged at key
      points in vertebrate evolution in order to infer derived and ancestral VDR
      functions of teleost paralogs. Species include the sea lamprey (Petromyzon
      marinus), a 1R jawless fish; the little skate (Leucoraja erinacea), a
      cartilaginous fish that diverged after the 2R event; and the Senegal bichir
      (Polypterus senegalus), a primitive 2R ray-finned fish. Saturation binding assays
      and gel mobility shift assays demonstrate high affinity ligand binding and
      classic DNA binding characteristics of VDR has been conserved across vertebrate
      evolution. Concentration response curves in transient transfection assays reveal
      EC50 values in the low nanomolar range, however maximum transactivational
      efficacy varies significantly between receptor orthologs. Protein-protein
      interactions were investigated using co-transfection, mammalian 2-hybrid assays,
      and mutations of coregulator activation domains. We then combined these results
      with our previous study of VDR paralogs from 3R teleosts into a bioinformatics
      analysis. Our results suggest that 1, 25D3 acts as a partial agonist in basal
      species. Furthermore, our bioinformatics analysis suggests that functional
      differences between VDR orthologs and paralogs are influenced by differential
      protein interactions with essential coregulator proteins. We speculate that we
      may be observing a change in the pharmacodynamics relationship between VDR and 1,
      25D3 throughout vertebrate evolution that may have been driven by changes in
      protein-protein interactions between VDR and essential coregulators. 

PMID- 25855983
TI  - Predictors of technical success and rate of complications of image-guided
      percutaneous transthoracic lung needle biopsy of pulmonary tumors.
AB  - PURPOSE: To investigate predictors of technical success and complications of
      computed tomography (CT)-guided percutaneous transthoracic needle biopsy of
      potentially malignant pulmonary tumors. MATERIAL AND METHODS: From 2008 to 2009,
      technical success and rate of complications of CT-guided percutaneous
      transthoracic lung needle biopsies of patients with suspicious pulmonary tumors
      were retrospectively evaluated. The influence on technical success and rate of
      complications was assessed for intervention-related predictors (lesion diameter,
      length of biopsy pathway, number of pleural transgressions, and needle size) and
      patient-related predictors (age, gender, reduced lung function). In addition,
      technical success and rate of complications were compared between different
      interventional radiologists. RESULTS: One hundred thirty-eight patients underwent
      biopsies by 15 interventional radiologists. The overall technical success rate
      was 84.1% and was significantly different between interventional radiologists
      (range 25%-100%; p<0.01). Intervention-related and patient-related predictors did
      not influence the technical success rate. The overall complication rate was 59.4%
      with 39.1% minor complications and 21.0% major complications. The rate of
      complications was influenced by lesion diameter and distance of biopsy pathway.
      Interventional radiologist-related rates of complications were not statistically
      different. CONCLUSIONS: Technical success of percutaneous, transthoracic lung
      needle biopsies of pulmonary tumors is probably dependent on the interventional
      radiologist. In addition, lesion diameter and length of biopsy pathway are
      predictors of the rate of complications.

PMID- 25855984
TI  - Effects of transcranial direct current stimulation on the control of finger force
      during dexterous manipulation in healthy older adults.
AB  - The contribution of poor finger force control to age-related decline in manual
      dexterity is above and beyond ubiquitous behavioral slowing. Altered control of
      the finger forces can impart unwanted torque on the object affecting its
      orientation, thus impairing manual performance. Anodal transcranial direct
      current stimulation (tDCS) over primary motor cortex (M1) has been shown to
      improve the performance speed on manual tasks in older adults. However, the
      effects of anodal tDCS over M1 on the finger force control during object
      manipulation in older adults remain to be fully explored. Here we determined the
      effects of anodal tDCS over M1 on the control of grip force in older adults while
      they manipulated an object with an uncertain mechanical property. Eight healthy
      older adults were instructed to grip and lift an object whose contact surfaces
      were unexpectedly made more or less slippery across trials using acetate and
      sandpaper surfaces, respectively. Subjects performed this task before and after
      receiving anodal or sham tDCS over M1 on two separate sessions using a cross-over
      design. We found that older adults used significantly lower grip force following
      anodal tDCS compared to sham tDCS. Friction measured at the finger-object
      interface remained invariant after anodal and sham tDCS. These findings suggest
      that anodal tDCS over M1 improved the control of grip force during object
      manipulation in healthy older adults. Although the cortical networks for
      representing objects and manipulative actions are complex, the reduction in grip
      force following anodal tDCS over M1 might be due to a cortical excitation
      yielding improved processing of object-specific sensory information and its
      integration with the motor commands for production of manipulative forces. Our
      findings indicate that tDCS has a potential to improve the control of finger
      force during dexterous manipulation in older adults. 

PMID- 25855985
TI  - Deiodinase knockdown during early zebrafish development affects growth,
      development, energy metabolism, motility and phototransduction.
AB  - Thyroid hormone (TH) balance is essential for vertebrate development. Deiodinase
      type 1 (D1) and type 2 (D2) increase and deiodinase type 3 (D3) decreases local
      intracellular levels of T3, the most important active TH. The role of deiodinase
      mediated TH effects in early vertebrate development is only partially understood.
      Therefore, we investigated the role of deiodinases during early development of
      zebrafish until 96 hours post fertilization at the level of the transcriptome
      (microarray), biochemistry, morphology and physiology using morpholino (MO)
      knockdown. Knockdown of D1+D2 (D1D2MO) and knockdown of D3 (D3MO) both resulted
      in transcriptional regulation of energy metabolism and (muscle) development in
      abdomen and tail, together with reduced growth, impaired swim bladder inflation,
      reduced protein content and reduced motility. The reduced growth and impaired
      swim bladder inflation in D1D2MO could be due to lower levels of T3 which is
      known to drive growth and development. The pronounced upregulation of a large
      number of transcripts coding for key proteins in ATP-producing pathways in D1D2MO
      could reflect a compensatory response to a decreased metabolic rate, also
      typically linked to hypothyroidism. Compared to D1D2MO, the effects were more
      pronounced or more frequent in D3MO, in which hyperthyroidism is expected. More
      specifically, increased heart rate, delayed hatching and increased carbohydrate
      content were observed only in D3MO. An increase of the metabolic rate, a decrease
      of the metabolic efficiency and a stimulation of gluconeogenesis using amino
      acids as substrates may have been involved in the observed reduced protein
      content, growth and motility in D3MO larvae. Furthermore, expression of
      transcripts involved in purine metabolism coupled to vision was decreased in both
      knockdown conditions, suggesting that both may impair vision. This study provides
      new insights, not only into the role of deiodinases, but also into the importance
      of a correct TH balance during vertebrate embryonic development. 

PMID- 25855986
TI  - Prognostic implication of human papillomavirus types and species in cervical
      cancer patients undergoing primary treatment.
AB  - High-risk human papillomavirus (HPV) types are associated with cervical cancer.
      It is well established that individual HPV types vary in oncogenicity, but
      current data on their prognostic implication remain controversial. We examined
      the association between HPV types/species and the survival of 236 Chinese women
      aged 26-87 (mean 54.4) years after receiving primary treatment for cervical
      cancer. Overall, 45.8% were of FIGO stage I, 41.9% stage II, and 12.3% stage III.
      The four most prevalent types found were HPV-16 (60.2%), HPV-18 (21.6%), HPV-52
      (11.9%), and HPV-58 (9.3%). Overall, 19.5% of patients had multiple-type
      infections, 78.4% harboured one or more alpha-9 species, and 28.8% harboured one
      or more alpha-7 species. After a median follow-up of 8.0 years, 156 (66.1%)
      patients survived. The 3-year overall survival rate was 75.5%. Factors
      independently associated with a poorer 3-year overall survival were age >60
      years, tumour size >4 cm, lymph node involvement and treatment with
      radiotherapy+/-chemotherapy. Univariate analysis showed HPV-16 single-type
      infection was associated with a marginally poorer disease-specific survival
      (71.6% vs. 87.0%, HR: 1.71, 95% CI = 1.01-2.90), whereas non-HPV-16 alpha-9
      species was associated with a better disease-specific survival (90.0% vs. 76.2%,
      HR: 0.36, 95% CI = 0.16-0.79). However, on multivariate analysis, HPV infection
      status irrespective of different grouping methods, including individual types,
      species, single-type or co-infection, did not carry any significant prognostic
      significance. In conclusion, we did not observe any association between infection
      with a particular HPV type/species and survival. An HPV type-based stratification
      in treatment and follow-up plan could not be recommended. 

PMID- 25855988
TI  - Successful emergency endovascular treatment of iatrogenic giant hepatic artery
      pseudoaneurysm.
AB  - Visceral artery aneurysms and visceral artery pseudoaneurysms frequently present
      as life-threatening emergencies. Hepatic artery pseudoaneurysm (HAP) is a very
      rare disease but in cases of complication, there is a very high mortality. The
      most common cause of HAP is iatrogenic trauma such as liver biopsy, transhepatic
      biliary drainage and cholecystectomy. We present a case of hepatic artery
      pseudoaneurysm presenting as hemobilia managed with cover stent of the aneurysm.

PMID- 25855989
TI  - Does perceived neighborhood walkability and safety mediate the association
      between education and meeting physical activity guidelines?
AB  - The role of neighborhood walkability and safety in mediating the association
      between education and physical activity has not been quantified. We used data
      from the 2010 and 2012 Communities Putting Prevention to Work Behavioral Risk
      Factor Surveillance System and structural equation modeling to estimate how much
      of the effect of education level on physical activity was mediated by perceived
      neighborhood walkability and safety. Neighborhood walkability accounts for 11.3%
      and neighborhood safety accounts for 6.8% of the effect. A modest proportion of
      the important association between education and physical activity is mediated by
      perceived neighborhood walkability and safety, suggesting that interventions
      focused on enhancing walkability and safety could reduce the disparity in
      physical activity associated with education level.

PMID- 25855987
TI  - Chronic Toxoplasma gondii in Nurr1-null heterozygous mice exacerbates elevated
      open field activity.
AB  - Latent infection with Toxoplasma gondii is common in humans (approximately 30% of
      the global population) and is a significant risk factor for schizophrenia. Since
      prevalence of T. gondii infection is far greater than prevalence of schizophrenia
      (0.5-1%), genetic risk factors are likely also necessary to contribute to
      schizophrenia. To test this concept in an animal model, Nurr1-null heterozygous
      (+/-) mice and wild-type (+/+) mice were evaluate using an emergence test,
      activity in an open field and with a novel object, response to bobcat urine and
      prepulse inhibition of the acoustic startle response (PPI) prior to and 6 weeks
      after infection with T. gondii. In the emergence test, T. gondii infection
      significantly decreased the amount of time spent in the cylinder. Toxoplasma
      gondii infection significantly elevated open field activity in both +/+ and +/-
      mice but this increase was significantly exacerbated in +/- mice. T. gondii
      infection reduced PPI in male +/- mice but this was not statistically
      significant. Aversion to bobcat urine was abolished by T. gondii infection in +/+
      mice. In female +/- mice, aversion to bobcat urine remained after T. gondii
      infection while the male +/- mice showed no aversion to bobcat urine. Antibody
      titers of infected mice were a critical variable associated with changes in open
      field activity, such that an inverted U shaped relationship existed between
      antibody titers and the percent change in open field activity with a significant
      increase in activity at low and medium antibody titers but no effect at high
      antibody titers. These data demonstrate that the Nurr1 +/- genotype predisposes
      mice to T. gondii-induced alterations in behaviors that involve dopamine
      neurotransmission and are associated with symptoms of schizophrenia. We propose
      that these alterations in murine behavior were due to further exacerbation of the
      altered dopamine neurotransmission in Nurr1 +/- mice. 

PMID- 25855990
TI  - Proxy reports about household members with increased confusion or memory loss,
      2011 Behavioral Risk Factor Surveillance System.
AB  - To provide information about the effects of increased confusion or memory loss
      (ICML) in households in the United States, we describe primary respondents'
      reports (proxy reports) about another person in their household experiencing
      ICML, using 2011 Behavioral Risk Factor Surveillance System (BRFSS) data. We used
      proxy reports on type of assistance needed, effects on functioning in daily
      activities, and whether confusion or memory was discussed with a health care
      professional, stratifying by age of the household member with ICML (18-50 y vs
      >=65 y). About 3% (n = 3,075 households) of primary respondents reported living
      with a household member with ICML; 75% of these household members needed some
      type of assistance, and nearly 60% had discussed ICML with a health care
      professional. Collecting proxy data about individuals in households may help
      paint a clearer picture of the characteristics of those experiencing cognitive
      decline and the potential needs of individuals and families.

PMID- 25855992
TI  - Effect of negative pressure wound therapy and external fixation in the treatment
      of femur fracture complicated by skin avulsion: a retrospective case series.
AB  - OBJECTIVE: The purpose of this study is to explore the clinical effects of
      negative pressure wound therapy (NPWT) and external fixation in the treatment of
      femur fracture complicated by skin avulsion. MATERIALS AND METHODS: Seven cases
      of comminuted fracture of the femur caused by traffic accidents and complicated
      by skin avulsion were retrospectively analyzed. After stabilization and treatment
      of life-threatening injuries, these 7 patients underwent wound debridement,
      external fixation of the fracture, and coverage of the wound with NPWT.
      Secondarily, the wounds were covered by skin-grafting. Patients were followed for
      an average of 12 months. RESULTS: After infection prophylaxis had been
      implemented and healthy granulation tissue had developed, each patient underwent
      secondary suture, freeskin grafting, or skin flap transfer. No wound had purulent
      drainage upon removal of the NPWT 4 to 7 days after placement. Secondary skin
      grafting was accomplished successfully in all 7 patients. Patients were followed
      for 6 to 15 months, and all wounds were well healed with no case of nonunion,
      osteomyelitis, or deformity at the site of union. CONCLUSION: External fixation
      with NPWT is effective treatment for femur fracture complicated by skin avulsion.
      The rate of infection is low and hospital stay is relatively short.

PMID- 25855991
TI  - Reported use and perceived understanding of sodium information on US nutrition
      labels.
AB  - INTRODUCTION: Comparing nutrition labels and choosing lower sodium foods are
      tactics to help reduce excessive sodium intake, a major risk factor for
      hypertension. Our objective was to assess US adult consumers' reported use and
      perceived understanding of sodium information on nutrition labels by
      sociodemographic and health status. METHODS: We analyzed responses to questions
      from 3,729 adults aged 18 years or older participating in 2 national cross
      sectional mail panel surveys in 2010. RESULTS: We found that 19.3% (95%
      confidence interval [CI], 17.2%-21.6%) of respondents agreed they were confused
      about how to figure out how much sodium is in the foods they eat; 57.9% (95% CI,
      55.4%-60.5%) reported that they or the person who shops for their food buy items
      labeled low salt or low sodium; and 46.8% (95% CI, 44.3%-49.4%) reported they
      check nutrition labels for sodium content as a tactic to limit salt. Consumers
      with a high school education or less were more likely than college graduates to
      report they were confused about sodium content on labels (adjusted odds ratio
      [AOR], 1.9; 95% CI, 1.4-2.8) and less likely to check labels for sodium as a
      tactic to limit salt intake (AOR, 0.7; 95% CI, 0.6-0.98). CONCLUSION: Most survey
      respondents in our study reported buying low sodium food items. However, a higher
      proportion of respondents with low education than respondents with high education
      reported confusion with and less use of sodium content information, suggesting
      enhanced efforts may be needed to assist this group. Opportunity exists for
      health care professionals to educate patients about using and understanding
      nutrition labels and consuming a diet consistent with the Dietary Approaches to
      Stop Hypertension (DASH) eating plan.

PMID- 25855993
TI  - The effect of a simple 3-step pressure relieving strategy for preventing pressure
      ulcers: an explorative longitudinal study from 2002-2011.
AB  - OBJECTIVE: Pressure ulcers (PUs) still form an important and distressing problem
      in Dutch nursing homes. Pressure ulcer prevention protocols are generally based
      on current guidelines. The authors developed an alternative 3-step protocol to
      help prevent pressure ulcers. The effects of this new 3-step protocol on the
      prevalence of pressure ulcers in patients at risk of developing PUs in the Avoord
      nursing homes in Etten-Leur/Zundert (Netherlands) were calculated. In addition,
      the protocol's general cost effects were explored. METHOD: Data on the prevalence
      of PUs and the use of preventive measures were derived from the annual
      independent International Prevalence Measurement of Care Problems of Maastricht
      University (Landelijke prevalentiemeting Zorgproblemen [LPZ]). This annual
      measurement was implemented in 1998 and measures care problems such as the
      prevalence of PUs and related preventive measures. Data on patients at risk of
      developing PUs at the Avoord nursing homes in Etten- Leur/Zundert (Netherlands)
      were analyzed and compared with national data between 2002 and 2011. RESULTS: The
      introduction of the 3-step protocol resulted in a significant reduction of the
      nosocomial prevalence of category 2-4 PUs. The prevalence was reduced from 8.7%
      to 0.5% during the first year and remained stable at about 2% throughout the rest
      of the study period. The prevalence at the national level also decreased during
      this period, but not as much, and was still significantly higher in 2011. The use
      of alternated systems decreased to almost 1%. Use of static air mattresses showed
      an almost linear rise in the Avoord nursing homes from the start of the
      implementation of the protocol, while the trend for both types of mattresses
      remained stable on a national level. Introducing the static air mattress instead
      of the more expensive alternating mattresses helped to reduce the mean daily
      costs of mattresses at the Avoord nursing homes by more than 70% compared to
      national figures. The workload of the nursing staff decreased as well due to the
      reduction of repositioning. CONCLUSION: The introduction of the 3-step protocol
      showed to be effective. The prevalence of PUs and the mean daily costs were
      reduced to, and have been sustained at, a significantly lower level.    .

PMID- 25855994
TI  - Changes of Transforming Growth Factor-beta1 and Extracellular Matrix in the Wound
      Healing Process of Rats Infected With Pseudomonas aeruginosa.
AB  - OBJECTIVE: This work aims to investigate the changes of transforming growth
      factor-beta1 (TGF-beta1) and extracellular matrix (ECM) proteins in rats with
      chronic skin ulcers infected with Pseudomonas aeruginosa. METHODS: Forty-eight
      female Wistar rats, aged 8 weeks, were randomly divided into a simple cutaneous
      wound group (group A) and a cutaneous wound plus Pseudomonas aeruginosa
      inoculation group (group B). On postoperative days 1, 3, 7, and 10, hematoxylin
      and eosin staining, real-time polymerase chain reaction, immunohistochemistry
      (IHC), and enzyme-linked immunosorbent assay (ELISA) methods were used to detect
      the epithelization rate, the mRNA, and the protein expressions of matrix
      metalloproteinases (MMP) 2, MMP-9, tissue inhibitors of metalloproteinases (TIMP)
      1, and TGF-beta1. RESULTS: Compared with group A, the expression of TGF-beta1 and
      the epithelization rate were delayed in group B. At 3 days postoperation, the
      expression of collagen III was reduced in group B. At 7 days postoperation, MMP-9
      had an extremely high expression but collagen and TIMP-1 had a low expression.
      Seven days after being infected with Pseudomonas aeruginosa, the expression of
      TGF-beta1 was reduced in the wounded skin of rats, and the dissolved ECM was much
      more than that synthesized in wounds. CONCLUSION: The authors' experiments
      suggest the wounded skin tissue infected with Pseudomonas aeruginosa delayed the
      expression of TGF-beta1, and then caused a change in the ECM biology relevant to
      fibrosis and regeneration, thus affecting the wound healing process.

PMID- 25855995
TI  - Surface acoustic wave patch therapy affects tissue oxygenation in ischemic feet.
AB  - INTRODUCTION: Transcutaneous oxygen pressure (TcPO2) less than 30 mm Hg at the
      toe leads to local tissue hypoxia and nonhealing wounds. Studies regularly
      illustrate that TcPO2 values are strong predictors of healing and can accurately
      demonstrate altered levels when extremities have restricted blood flow. The
      objective of this study was to evaluate the effectiveness of surface acoustic
      wave (SAW) in ischemic feet on local tissue oxygenation. METHODS: Ten patients,
      ranging from 40-75 years of age and suffering from critical limb ischemia (CLI)
      were selected from a vascular surgery clinic to undergo evaluation with a
      PainShield SAW Patch device (NanoVibronix Inc, Melville, NY). Patients were
      treated once with 96 Khz of SAW for 30 minutes. All patients had an ankle
      brachial index of < 0.4 mm Hg. Two patients (patients 1 and 8) had necrosis of at
      least 2 toes on the affected limb and were given the device for nightly use for 1
      month. RESULTS: Through usage of SAW there was a significant increase in all
      patients' saturation values. The recorded baseline in both patients with necrotic
      toes almost doubled and during usage there was still a measurable increase in
      oxygen saturation. In both of these patients the subjective pain measures dropped
      significantly. Pain, as assessed by the Visual Analog Scale, dropped from 9 to 2
      for patient 1 and from 8 to 3 for patient 8. Patient 1 went from 5 methadone
      treatments per day to only 1 per day starting in week 3. Patient 8 did not change
      their pain medication regimen. CONCLUSION: Surface acoustic waves as delivered in
      this study had a positive effect on tissue oxygenation and saturation in ischemic
      feet. In lower extremities that are not surgical candidates or are either in the
      pre- or postsurgical environment, an SAW patch device is a good therapy in
      elevating the extremities' O2 saturation.

PMID- 25855996
TI  - Teledermatology may play a role in reducing severity of pressure ulcers in both
      rural and urban settings.
AB  - INTRODUCTION: Teledermatology is already thought to be a valuable tool for
      patients in rural areas due to their lack of easy access to specialty care
      providers. This study explored the benefit of teledermatology for bedridden
      patients living in both rural and urban areas. METHODS: The following 4 studies
      were evaluated: 1) evaluation of conditions of 83 patients who had developed
      pressure ulcers before being admitted to the hospital; 2) evaluation of the
      circumstances of 53 patients with pressure ulcers who received home care; 3)
      survey of 321 home care nurses regarding their concerns about wound care; and 4)
      results of a teledermatology system aiming at early intervention for chronic
      wound treatment. RESULTS: 1) Sixtythree percent of patients who developed
      pressure ulcers were over 70 years old, 84% of them were bedridden, and 66%
      developed at home. 2) Seventy-four percent of patients who received home care and
      developed pressure ulcers lived alone or with an elderly spouse, and only 19%
      consulted a specialist. 3) A survey of 321 home care nurses revealed that they
      have difficulties with consulting a specialist, with their complaints against
      home care doctors amounting to 70% of their responses. 4) Seventeen consultations
      were sent to a new teledermatology system, 82% by patients, families, and home
      care nurses. About half of these patients were bedridden, and 82% were currently
      living at home. Twelve cases (70.6%) were from urban areas. CONCLUSION: Because
      of the potential for teledermatology to prevent the worsening of ulcers,
      teledermatological wound consultations should be utilized by all bedridden
      patients who have a wound.

PMID- 25855997
TI  - Delaying the Onset of Resistance Formation: Effect of Manipulating Dose,
      Wavelength, and Rate of Energy Delivery of 405-, 464-, and 850-Nanometer Light
      for Staphylococcus aureus.
AB  - OBJECTIVE: To determine whether manipulation of dose, wavelength, and rate of
      energy delivery could delay the onset of previously demonstrated Staphylococcus
      aureus resistance to blue light. METHODS: The organism was treated in vitro with
      405 nm, 464 nm, and combined 464 nm and with 850 nm light emitted from a
      supraluminous diode (SLD) array. Doses of 9 J/cm2 and 30 J/cm2 were used. Rates
      of energy delivery were also varied from 10 mW/cm2 to 125 mW/cm2. Seven stages
      were employed to test for resistance formation. Colony counts were performed and
      compared to untreated controls using Student t tests and one-way ANOVA with Tukey
      post hoc analysis. RESULTS: A best dose, wavelength, and rate of delivery
      combination was determined at each stage and it did produce a significant kill
      rate (P <= 0.05) at each stage. Analysis of variance demonstrated that no loss of
      effectiveness (formation of resistance) occurred over the 7 stages. CONCLUSIONS:
      Appropriate combinations of dose, wavelength, and rate of energy delivery can
      delay resistance formation to light as a bactericidal agent for S. aureus.    .

PMID- 25855998
TI  - Cellular characterization of wound exudate as a predictor of wound healing
      phases.
AB  - This study was designed to characterize the cell populations present in wound
      exudate, to examine the validity of these populations in identifying the wound
      phase to find possible predictors of healing, and to anticipate events in favor
      of a more rapid recovery. METHODS: Fourteen patients who presented with
      postsurgical wounds with negative pressure therapy were included in the study.
      The authors collected samples from 51 wounds in the inflammatory phase and 29 in
      the proliferative phase. RESULTS: The number of neutrophils and platelets in the
      exudate collected from wounds in the inflammatory phase was significantly higher
      (P < 0.05), while the number of lymphocytes, eosinophils, and basophils was
      significantly higher in exudate from wounds in the proliferative phase. The
      receiver operating characteristic analysis gives an area under curve of 0.815 for
      neutrophils (P < 0.001, CI: 0.698-0.933) and 0.760 for platelets (P < 0.001, CI:
      0.647-0.873). The results showed 45.8% of neutrophils have a sensitivity of 84.4%
      and a specificity of 66.7% for detecting the inflammatory phase. For platelets, a
      level of 135.000 has a sensitivity of 71.1% and a specificity of 61.1%. The
      percentage of neutrophils and the platelet levels remained significant predictors
      of the inflammatory phase. CONCLUSION: The study results suggest that platelets
      and neutrophils in wound exudate might be useful prognostic indicators of the
      inflammatory or proliferative phase of wound healing.

PMID- 25855999
TI  - Effects of autologous keratinocyte cell spray with and without chitosan on third
      degree burn healing: an animal experiment.
AB  - Treatment of extensive third degree burns, especially in the case of limited skin
      donor sites for obtaining autologous split-thickness skin grafts (STSG), has led
      to in vitro expansion of keratinocytes. Cultured epidermal autograft (CEA) sheets
      have been used for burn treatment for several years. However, time consuming
      processes of isolation and cultivation of keratinocytes, as well as difficult
      procedures of detachment of CEA from cultured flasks, led scientists to develop
      the technique of spraying cultured single keratinocytes (CSK) instead of using
      CEA. Chitosan is a well-known wound dressing biomaterial that has both biological
      and medical applications. In this study, the application method of CSK was used
      to determine whether there would be any significant difference between the
      treatment of burns with CSK alone in comparison to burns treated with CSK and
      covered with chitosan gel at a neutral pH. MATERIALS AND METHODS: Thirty male
      Wistar rats were selected and their keratinocytes were isolated and cultured from
      small skin biopsy. Rats were divided randomly into 3 equal groups and 3 full
      thickness round burn wounds were created on their backs. Rats were treated with
      either normal saline (control group), CSK (test group A), or CSK + neutral
      chitosan (CSK+ NCH) (test group B). The wounds were photographed on days 0, 3, 5,
      7, 10, and 14, and the percentage of wound contraction was calculated with an
      image analyzer. Biopsy samples were taken for histological studies. RESULTS: The
      results showed faster wound contraction for test groups A and B during the 14-day
      period than the control group (P < 0.05). Also, more contraction was found in
      test groups A and B in 7 days (P < 0.05). Histological observations showed
      significant difference in inflammation and fibrotic tissue formation between
      groups, but other parameters did not show any remarkable difference. CONCLUSION:
      Based on the findings of this study, the authors concluded that chitosan can
      prevent cells from dripping out of the wound, speed up wound contraction, and
      extend fibrotic tissue formation. Chitosan did not, however, have any effect on
      fastening the reepithelialization and granulation tissue formation during the
      first 14 days.

PMID- 25856000
TI  - Magnetic-assembly mechanism of superparamagneto-plasmonic nanoparticles on a
      charged surface.
AB  - One-dimensional magnetoplasmonic nanochains (MPNCs) were self-assembled using Au
      coated Fe3O4 core-shell superparamagnetic nanoparticles (Fe3O4@Au NPs) by
      applying an external static magnetic field. The assembly mechanism of the
      Fe3O4@Au NPs was investigated thoroughly, revealing that substrate-particle
      interactions, van der Waals forces, and magnetic forces play important roles in
      the formation and control of the MPNCs. Magnetic force microscopy (MFM) and
      vibrating sample magnetometry (VSM) were used to study the magnetic properties of
      the MPNCs, which were compared with those of Fe3O4 nanochains. 

PMID- 25856001
TI  - 51V NMR Crystallography of Vanadium Chloroperoxidase and Its Directed Evolution
      P395D/L241V/T343A Mutant: Protonation Environments of the Active Site.
AB  - Vanadium-dependent haloperoxidases (VHPOs) perform two-electron oxidation of
      halides using hydrogen peroxide. Their mechanism, including the factors
      determining the substrate specificity and the pH-dependence of the catalytic
      rates, is poorly understood. The vanadate cofactor in the active site of VHPOs
      contains "spectroscopically silent" V(V), which does not change oxidation state
      during the reaction. We employed an NMR crystallography approach based on (51)V
      magic angle spinning NMR spectroscopy and Density Functional Theory, to gain
      insights into the structure and coordination environment of the cofactor in the
      resting state of vanadium-dependent chloroperoxidases (VCPO). The cofactor
      environments in the wild-type VCPO and its P395D/L241V/T343A mutant exhibiting 5
      100-fold improved catalytic activity are examined at various pH values. Optimal
      sensitivity attained due to the fast MAS probe technologies enabled the
      assignment of the location and number of protons on the vanadate as a function of
      pH. The vanadate cofactor changes its protonation from quadruply protonated at pH
      6.3 to triply protonated at pH 7.3 to doubly protonated at pH 8.3. In contrast,
      in the mutant, the vanadate protonation is the same at pH 5.0 and 8.3, and the
      cofactor is doubly protonated. This methodology to identify the distinct
      protonation environments of the cofactor, which are also pH-dependent, could help
      explain the different reactivities of the wild-type and mutant VCPO and their pH
      dependence. This study demonstrates that (51)V-based NMR crystallography can be
      used to derive the detailed coordination environments of vanadium centers in
      large biological molecules. 

PMID- 25856002
TI  - Polymorphisms of the TGFBRAP1 gene in relation to blood pressure variability and
      plasma TGF-beta1.
AB  - TGF-beta receptor-associated protein 1 (TGFBRAP1), as a chaperone, binds Smad4 to
      participate in vascular development and remodeling which is closely related to
      the aetiology of essential hypertension (EH). Herein, the main aim of this study
      is to investigate the genetic susceptibility of TGFBRAP1 to hypertension. A case
      control study comprising 2012 hypertension cases and 2210 controls was used to
      generate the hypothesis of the association of TGFBRAP1 gene with EH and another
      case-control study in a children population then proceeds to further replicate
      the association. Logistic regression model was used to adjust confounding factor
      for EH and general linear model (GLM) was applied to compare blood pressure
      levels and plasma TGF-beta1 levels between genotypes in cases and controls. There
      was no statistical association with EH after the covariates were controlled for.
      However, quantitative trait analysis indicated that DBP had a linear decrease
      with the variations of rs2679860 (p = 0.005) after adjustment for confounding
      factor but the direction of this genetic effect was opposite of that in the
      children population. And normally distributed square root of TGF-beta1 (pg/ml)
      had a linear increased with the variations of rs2679860 (p = 0.042) after
      adjusting covariates. Our finding supports the association of rs2679860
      polymorphisms of TGFBRAP1 and DBP variation as well as plasma levels of TGF-beta1
      and that suggests the variation of rs2679860 might influence the direct
      modulatory effect of TGF-beta1 on the blood pressure by regulating the plasma
      levels of TGF-beta1. 

PMID- 25856003
TI  - Resimulation of noise: a precision estimator for least square error curve-fitting
      tested for axial strain time constant imaging.
AB  - Recent elastography techniques focus on imaging information on properties of
      materials which can be modeled as viscoelastic or poroelastic. These techniques
      often require the fitting of temporal strain data, acquired from either a creep
      or stress-relaxation experiment to a mathematical model using least square error
      (LSE) parameter estimation. It is known that the strain versus time relationships
      for tissues undergoing creep compression have a non-linear relationship. In non
      linear cases, devising a measure of estimate reliability can be challenging. In
      this article, we have developed and tested a method to provide non linear LSE
      parameter estimate reliability: which we called Resimulation of Noise (RoN). RoN
      provides a measure of reliability by estimating the spread of parameter estimates
      from a single experiment realization. We have tested RoN specifically for the
      case of axial strain time constant parameter estimation in poroelastic media. Our
      tests show that the RoN estimated precision has a linear relationship to the
      actual precision of the LSE estimator. We have also compared results from the RoN
      derived measure of reliability against a commonly used reliability measure: the
      correlation coefficient (CorrCoeff). Our results show that CorrCoeff is a poor
      measure of estimate reliability for non-linear LSE parameter estimation. While
      the RoN is specifically tested only for axial strain time constant imaging, a
      general algorithm is provided for use in all LSE parameter estimation. 

PMID- 25856005
TI  - Unmet needs in the treatment of chronic lymphocytic leukemia: introduction.

PMID- 25856004
TI  - Coexistence of monochalocogen and dichalocogen ions in BiSe2 and BiS2 crystals
      prepared at high pressure.
AB  - A single crystal of bismuth diselenide, BiSe2, containing both monochalcogen
      (Se(2-)) and dichalcogen (Se2(2-)) ions, was prepared at a high pressure of 5.5
      GPa. Its crystal structure, substitution chemistry, and physical properties were
      investigated. X-ray analysis showed that BiSe2 is in a monoclinic system (space
      group C2/m) with the following lattice parameters: a = 16.740(3) A, b =
      4.1410(11) A, c = 12.027(3) A, and beta = 127.658(13) degrees . A crystal
      structure of BiSe2 can be viewed as a layered structure with stacks of neutral
      BiSe2 blocks along the c-axis, or alternatively as a quasi-one-dimensional
      structure with double chains of BiSe5 pyramids along the b-axis. Each Bi is
      coordinated with three Se(2-) ions and two Se2(2-) ions, and the bond valence
      analysis indicated that Bi was trivalent. BiSe2 and BiS2 form a solid solution in
      the whole range while retaining the same structure, and the partial substitution
      of Sb for Bi is also achieved at 10%. All the compounds show a semiconducting
      property and diamagnetism that can be attributed to the closed-shell ion core. In
      spite of the compositional analogy with Bi2Se3, BiSe2 is proven by the first
      principles calculations not to be a topological insulator. 

PMID- 25856006
TI  - Traditional treatment approaches in chronic lymphocytic leukemia.

PMID- 25856008
TI  - Unmet needs in the treatment of chronic lymphocytic leukemia: general discussion.

PMID- 25856007
TI  - Targeted agents in chronic lymphocytic leukemia.

PMID- 25856009
TI  - Discovery of I-BRD9, a Selective Cell Active Chemical Probe for Bromodomain
      Containing Protein 9 Inhibition.
AB  - Acetylation of histone lysine residues is one of the most well-studied post
      translational modifications of chromatin, selectively recognized by bromodomain
      "reader" modules. Inhibitors of the bromodomain and extra terminal domain (BET)
      family of bromodomains have shown profound anticancer and anti-inflammatory
      properties, generating much interest in targeting other bromodomain-containing
      proteins for disease treatment. Herein, we report the discovery of I-BRD9, the
      first selective cellular chemical probe for bromodomain-containing protein 9
      (BRD9). I-BRD9 was identified through structure-based design, leading to greater
      than 700-fold selectivity over the BET family and 200-fold over the highly
      homologous bromodomain-containing protein 7 (BRD7). I-BRD9 was used to identify
      genes regulated by BRD9 in Kasumi-1 cells involved in oncology and immune
      response pathways and to the best of our knowledge, represents the first
      selective tool compound available to elucidate the cellular phenotype of BRD9
      bromodomain inhibition. 

PMID- 25856010
TI  - Direct 765 nm Optical Excitation of Molecular Oxygen in Solution and in Single
      Mammalian Cells.
AB  - Singlet oxygen, O2(a(1)Deltag), the first excited electronic state of molecular
      oxygen, is an important reactive oxygen species. Its chemistry plays a role in
      processes ranging from polymer degradation to cell death. Although O2(a(1)Deltag)
      is routinely produced through natural events, including photosensitized processes
      mediated by organic chromophores, the controlled and selective laboratory
      production of O2(a(1)Deltag) remains a challenge, particularly in biological
      systems. Here we exploit the fact that ground-state oxygen, O2(X(3)Sigmag(-)),
      absorbs 765 nm light to selectively produce O2(b(1)Sigmag(+)) which, in turn,
      decays to O2(a(1)Deltag). We have quantified this process in different solvents
      using the time-resolved 1275 nm O2(a(1)Deltag) phosphorescence as an optical
      probe. Most importantly, 765 nm falls in the so-called "biological window", where
      endogenous chromophores minimally absorb. We show that femtosecond-laser-based,
      spatially resolved 765 nm irradiation of human tumor cells induces O2(a(1)Deltag)
      mediated cell death. We thus provide an accessible tool for the controlled
      sensitizer-free production and study of O2(a(1)Deltag) in complex biological
      systems. 

PMID- 25856011
TI  - Congestive heart failure during induction with anthracycline-based therapy in
      patients with acute promyelocytic leukemia.
AB  - BACKGROUND: Acute promyelocytic leukemia (APL) is a highly curable malignancy.
      However, 30% of patients die during therapy induction from bleeding,
      differentiation syndrome (DS), and/or infection. Recommendations suggest that
      congestive heart failure (CHF) is a presenting feature of DS. OBJECTIVE: To
      assess the incidence of CHF during induction in patients with APL. METHODS: A
      retrospective chart review was performed of patients diagnosed with APL from
      December 2004 to July 2013 and managed at Georgia Regents University Cancer
      Center. Baseline and follow-up ejection fractions (EF) were recorded and patients
      with a drop in EF during the induction period were evaluated. RESULTS: Of the 40
      evaluable patients, 37 received idarubicin-based chemotherapy. 16 of the 37
      patients had a repeat ECHO for suspected cardiomyopathy, and 6 of the 16 patients
      (37.5%) demonstrated a decrease in EF (absolute drop, 10%-35%). The cardiac
      function recovered completely in 4 patients and partially in 1 patient. Gender,
      history of hypertension, and body mass index did not seem to correlate with
      incidence of CHF. LIMITATIONS: The patient population is very small given the
      rarity of the disease. Present practice patterns do not routinely address CHF in
      the differential diagnosis. CONCLUSIONS: Patients with APL are at risk for
      cardiac toxicity for a number of reasons, including cytokine storm and
      inflammatory state, use of anthracyclines, and DS. The clinical presentation of
      DS most commonly involves dyspnea and fluid retention, which are also symptoms of
      heart failure. Prompt cardiac evaluation should be undertaken to rule out CHF in
      APL patients who are going to receive an anthracycline-based therapy, because
      early intervention may result in an improved outcome.

PMID- 25856012
TI  - Impact of aprepitant on emesis control, dose intensity, and recurrence-free
      survival in a population-based cohort of head and neck cancer patients receiving
      high-dose cisplatin chemotherapy.
AB  - BACKGROUND: Standard care for locally advanced head and neck cancer (HNC)
      patients consists of high-dose cisplatin with radiation to prolong recurrence
      free survival (RFS). However, poorly controlled emesis can compromise optimal
      dose intensity (DI) and affect disease control. OBJECTIVE: To evaluate the impact
      of aprepitant on emesis control, DI, and RFS. METHODS: HNC patients treated at
      the British Columbia Cancer Agency were analyzed. Kaplan-Meier method and
      adjusted Cox proportional hazard models were used to evaluate RFS in aprepitant
      users. To control for selection bias, a propensity score analysis was conducted.
      RESULTS: A total of 192 HNC patients were included: 141 received aprepitant
      prophylaxis. The aprepitant-treated and untreated groups were comparable in mean
      age (56.3 vs 58.1 years), male gender (82.3% vs 86.3%), tumor location, and
      number of metastatic sites. However, more patients in the aprepitant group than
      in the untreated group had surgically resectable disease (31.2% vs 15.7%,
      respectively) and better performance status (ECOG 0/1, 87.9% vs 76.4%). Less
      emesis was reported in the aprepitant group (21.3% vs 28.0%). Patients in the
      treated group were also more likely to complete 3 cycles of high-dose cisplatin
      (OR, 2.3; P = .03). The propensity score adjusted Cox regression analysis
      suggested a reduced risk of disease recurrence in patients who received
      aprepitant (HR, 0.47; 95% CI, 0.17- 1.28). LIMITATIONS: Potential confounders
      such as other diseases or treatments that may have influenced the presence of
      nausea/emesis symptoms. CONCLUSION: Aprepitant contributed to improved emesis
      control, enhanced DI, and better adherence to cisplatin chemotherapy.

PMID- 25856013
TI  - Chemotherapy-induced peripheral neuropathy and impact on quality of life 6 months
      after treatment with chemotherapy.
AB  - BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a major dose
      limiting toxicity of cytostatics. With improved survival among cancer patients,
      CIPN may have a major impact on quality of life (QoL) of cancer survivors.
      OBJECTIVE: To determine the occurrence of CIPN induced by oxaliplatin and taxanes
      and its impact on QoL median 6 months after chemotherapy. METHODS: All patients
      who received their last treatment with oxaliplatin or taxanes in 2 consecutive
      years in the Maxima Medical Centre, the Netherlands, were eligible for the study.
      Neurotoxicity and its effect on QoL was assessed with the recently developed
      Chemotherapy Induced Neurotoxicity Questionnaire (CINQ) and the Functional
      Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG
      Ntx) median 6 months after cessation of therapy. RESULTS: Of the 58 eligible
      patients, 43 (74.1%) completed the questionnaire. After a median follow-up of 6.5
      months after cessation of therapy, most of the patients experienced neurotoxicity
      in the upper and lower extremities (78.8% and 89.7%, respectively). Overall, the
      most-reported complaints included numbness and tingling in hands as well as feet,
      suffering from cold feet, and trouble distinguishing objects in the hands.
      Housekeeping difficulties were reported in 12.8% of patients, and 20.5% of
      patients became more dependent on others because of the neurotoxicity. Overall,
      QoL was negatively affected by the impact of CIPN in 48.6% of patients.
      LIMITATIONS: Due to the small sample size selection bias cannot be ruled out and
      no data about CIPN during treatment were available. Conclusions After a median
      follow-up of 6.5 months after cessation of therapy with oxaliplatin or taxanes,
      CIPN is common and leads to impairment in patient QoL. More research is needed to
      assess the impact of neurotoxicity on QoL. CONCLUSIONS: After a median follow-up
      of 6.5 months after cessation of therapy with oxaliplatin or taxanes, CIPN is
      common and leads to impairment in patient QoL. More research is needed to assess
      the impact of neurotoxicity on QoL.

PMID- 25856014
TI  - Superior vena cava syndrome as an initial presentation of low-grade follicular
      lymphoma.
AB  - Superior vena cava (SVC) syndrome refers to a constellation of symptoms produced
      by the obstruction of blood flow through the SVC, resulting in symptoms of
      dyspnea, facial and upper-extremity edema, cough, chest pain, and dysphagia.1
      Malignancies represent 60%-85% of the etiologies of SVC syndrome. Cumulatively,
      lymphoma and lung cancer represent 95% of malignancy-related SVC syndrome
      etiologies, with non-small-cell lung cancer (NSCLC) reported in about 50% of
      cases, small-cell lung cancer (SCLC) in about 25%, and non-Hodgkin lymphoma (NHL)
      in 10 % of all cases. 

PMID- 25856015
TI  - Diagnostic and Therapeutic Challenges.

PMID- 25856016
TI  - Application of Blue Light (Red-Free) Angiography Using Confocal Scanning Laser
      Ophthalmoscope.

PMID- 25856017
TI  - RISK OF RETINAL VEIN OCCLUSION IN PATIENTS WITH PSORIASIS: A Population-Based
      Cohort Study.
AB  - PURPOSE: To investigate the risk of developing retinal vein occlusion (RVO) in
      patients with psoriasis. METHODS: In this retrospective population-based cohort
      study, 30,198 patients with psoriasis (Psoriasis((+)) group) and 30,198 controls
      without psoriasis (Psoriasis((-)) group) between 2001 and 2006 from the Taiwan
      National Health Insurance Research Database were selected. RESULTS: The incidence
      of RVO was 1.46 times higher in the Psoriasis((+)) group than in the Psoriasis((
      )) group (3.61 vs. 2.47/10,000 person-years) (adjusted hazard ratio = 1.50; 95%
      confidence interval = 1.07-2.10) calculated using Cox proportional hazard
      regression. Age was an independent risk factor for RVO (adjusted hazard ratio:
      11.9 for patients 65 years or older vs. 1.00 for those 0-49 years old). In the 65
      years or older Psoriasis((+)) group, the incidence of developing RVO was 1.97
      times higher (95% confidence interval = 1.19-3.26) than in the 65 years or older
      Psoriasis((-)) group. In Psoriasis((+)) women, the incidence of developing RVO
      was 1.82 times higher (95% = 1.05-3.14) than in Psoriasis((-)) women. For the
      subgroup with comorbid hypertension, the incidence of developing RVO was 2.07
      times higher (95% confidence interval = 1.22-3.50) in the Psoriasis((+)) group
      than in the Psoriasis((-)) group. CONCLUSION: Psoriasis was significantly
      associated with a higher risk of developing RVO.

PMID- 25856018
TI  - Correspondence.

PMID- 25856019
TI  - Reply: To PMID 24457977.

PMID- 25856020
TI  - Safe and Effective Electroconvulsive Therapy Using Multiple Parameters Over 5
      Years in a Patient With Deep Brain Stimulator.

PMID- 25856022
TI  - Highlights in advanced prostate cancer from the 2013 American Urological
      Association Annual Meeting and the 2013 American Society of Clinical Oncology
      Annual Meeting.

PMID- 25856021
TI  - A Survey of the Practice of Electroconvulsive Therapy in South Africa.
AB  - OBJECTIVES: The aim of this study was to describe the contemporary practice of
      electroconvulsive therapy (ECT) in South Africa. METHODS: A 36-item questionnaire
      was sent to all hospitals that practiced ECT in a 12-month period between 2011
      and 2012. RESULTS: Forty-two institutions had an ECT machine on site, but 13
      institutions reported nonuse. Electroconvulsive therapy services were available
      in only 6 of the 9 provinces. Questionnaires were sent to the 29 active sites.
      Twenty-four units (82.8%) responded, and of these, 20 institutions (68.9%)
      responded to question on the number of patients treated with ECT. Pre-ECT
      procedures commonly involved informed consent, a physical examination, and basic
      blood investigations. Bilateral, unilateral, and bifrontal electrode placements
      were used, whereas dose titration methods and seizure monitoring were used by
      most respondents. The number of persons treated with ECT per 10,000 persons per
      year was 0.22, whereas the number of ECT procedures performed per 10,000 persons
      per year was 1.19. The most common indication for ECT was depression, with most
      patients being between the ages of 18 and 59 years. CONCLUSIONS: The
      characteristics and rate of ECT utilization in South Africa have been determined
      and generally emulated international guidelines and trends. However,
      accessibility to services and aspects such as training and accreditation could be
      improved.

PMID- 25856023
TI  - Highlights in advanced prostate cancer from the 2013 American Urological
      Association Annual Meeting and the 2013 American Society of Clinical Oncology
      Annual Meeting: commentary.

PMID- 25856025
TI  - Health policy... So what?

PMID- 25856026
TI  - Technology and patient safety.

PMID- 25856027
TI  - Ethical and legal aspects of inappropriate (ghost) authorship.

PMID- 25856028
TI  - Psychometric instrumentation: reliability and validity of instruments used for
      clinical practice, evidence-based practice projects and research studies.
AB  - It is important for CNSs and other APNs to consider the reliability and validity
      of instruments chosen for clinical practice, evidence-based practice projects, or
      research studies. Psychometric testing uses specific research methods to evaluate
      the amount of error associated with any particular instrument. Reliability
      estimates explain more about how well the instrument is designed, whereas
      validity estimates explain more about scores that are produced by the instrument.
      An instrument may be architecturally sound overall (reliable), but the same
      instrument may not be valid. For example, if a specific group does not understand
      certain well-constructed items, then the instrument does not produce valid scores
      when used with that group. Many instrument developers may conduct reliability
      testing only once, yet continue validity testing in different populations over
      many years. All CNSs should be advocating for the use of reliable instruments
      that produce valid results. Clinical nurse specialists may find themselves in
      situations where reliability and validity estimates for some instruments that are
      being utilized are unknown. In such cases, CNSs should engage key stakeholders to
      sponsor nursing researchers to pursue this most important work.

PMID- 25856029
TI  - Opioid abuse, misuse, and death: the promises and limitations of drug barrier
      technology now and in the future.

PMID- 25856030
TI  - Collaborative care approaches for people with severe mental illness.

PMID- 25856031
TI  - Win-win negotiation.

PMID- 25856032
TI  - Creating a sustainable, interprofessional-team training program: initial results.
AB  - PURPOSE/OBJECTIVES: The purpose of this program evaluation was to explore whether
      incorporating deliberate learning concepts, through the use of simulated patient
      scenarios to teach interprofessional collaboration skills to a healthcare team on
      one acute-care hospital unit, would improve the resuscitation response in the
      first 5 minutes on that unit. DESIGN/SETTING: This was a pilot program evaluation
      utilizing a unit-based, clinical nurse specialist in the deployment of an
      interprofessional educational program involving simulation on an acute medical
      floor in a large tertiary-care hospital. SAMPLE: Eighty-four staff members
      participated in 17 simulations. The sample included first-year internal-medicine
      residents, registered nurses, respiratory therapists, and patient care
      technicians. METHODS: This was a program evaluation that used the TeamSTEPPS
      Teamwork Perceptions Questionnaire (T-TPQ) (Classroom slides: TeamSTEPPS
      essentials; http://www.ahrq.gov/professionals/education/curriculum
      tools/teamstepps/instructor/essentials/slessentials.html#s3) during the
      presimulation/postsimulation sessions to assess the participants' perceptions of
      teamwork. Expected intervention behaviors were collected through observations of
      participants in the simulations and compared with the American Heart Association
      guidelines (Circulation 2010;122:S685-S670, S235-S337). Common perceptions of
      participants regarding the experience were obtained through open-ended evaluation
      questions. RESULTS: Fifty-three participants completed the pre- and post-T-TPQ.
      Mean scores in the leadership category of T-TPQ decreased significantly (P =
      .003) from the pretest (median, 2.167) to the T-TPQ posttest (median, 2.566).
      Only 35% of the groups administered a defibrillation during the ventricular
      fibrillation simulation scenario, and only 1 group delivered this shock within
      the American Heart Association's recommended time frame of 2 minutes (Circulation
      2010;122:S235-S337). CONCLUSION: A single resuscitation simulation was not enough
      interventional dosage for staff to improve the resuscitation process. A
      longitudinal study should be conducted to determine the effectiveness of the
      program after staff members have repeated the program multiple times.
      IMPLICATIONS: A unit-based quality-improvement simulation training program could
      help improve the first-5-minute response and resuscitation skills of staff by
      increasing the frequency of unit-based training overseen by the unit's clinical
      nurse specialist.

PMID- 25856033
TI  - Clinical nurse specialist prescriber characteristics and challenges in Oregon.
AB  - PURPOSE/OBJECTIVES: The purpose of this study was to assess role characteristics
      of clinical nurse specialists (CNSs) with prescriptive authority in Oregon 10
      years after passage of Senate Bill 460. Factors examined included role
      preparation and mentorship, use and maintenance of authority, prescribing
      benefits and barriers, and types of drugs/nondrugs prescribed. DESIGN: This study
      was a descriptive survey using both quantitative and qualitative analysis.
      SAMPLE: The sample was obtained from a list provided on June 13, 2014, by the
      Oregon State Board of Nursing of all CNSs in Oregon who had ever been granted
      prescriptive authority (n = 40). Twenty-nine with active authority, 7 with
      expired authority, and 4 with inactive status were sampled. METHODS: E-mail
      distribution with Qualtrics software was released on June 27, 2014. Reminder e
      mails were sent at 1 and 2 weeks. Of the 38 e-mails successfully delivered, 23
      responses were received for a total response rate of 60%. RESULTS: Clinical nurse
      specialists successfully maintained their authority in Oregon and felt well
      prepared for their role. Their prescribing mentorship included nurse and nonnurse
      prescribers. They were most likely to have ever prescribed psychiatric,
      noncontrolled analgesics and durable medical equipment. They most frequently
      prescribed nutrition/electrolytes/fluids, durable medical equipment, and
      controlled analgesics. Lapse in authority was attributed to constraints regarding
      certification or credentialing in the role. CONCLUSIONS: Clinical nurse
      specialists uniformly expressed benefits from prescriptive authority. There were
      no differences in perceptions of preparation based on type of mentorship or
      educational modality for completion of prescribing requirements. There were
      systems barriers including lack of employer and colleague support to use of
      authority. Durable medical equipment authority is important to the CNS role.
      IMPLICATIONS: Clinical nurse specialists valued and maintained their prescriptive
      authority despite barriers. Further research is recommended to support success
      for CNS prescribers from multiple settings and specialties.

PMID- 25856034
TI  - Simulation education: early identification of patient physiologic deterioration
      by acute care nurses.
AB  - PURPOSE/OBJECTIVES: The specific aim of this quality improvement project was to
      improve acute care nurses' ability to assess deteriorating patients, recognize
      signs of instability and immediate critical treatment, and escalate care in a
      timely manner. BACKGROUND: Early identification of and treatment of patient
      deterioration can improve patient and hospital/system spheres of clinical nurse
      specialist influence. RATIONALE: An earlier response to clinical deterioration
      may result in improved patient outcomes. DESCRIPTION: A clinical nurse specialist
      devised and implemented a 2-phase education program-e-learning module and
      simulation scenarios utilizing a PDSA (plan, do, study, act) cycle framework.
      Education effectiveness was assessed by knowledge and performance of critical
      activities for instability identification, notification, and recognition,
      including an SBAR (situation, background, assessment, recommendation)
      communication approach. The simulation phase included group participation in 2
      instability scenarios with an intervening debriefing using a gather-analyze
      summarize (GAS) approach. Effectiveness was assessed via pre-education and
      posteducation knowledge surveys and assessment of time to critical actions in the
      simulation scenarios. Time to achievement of critical actions in the scenarios
      was determined by quantifying the baseline time for the simulation to run and the
      percentage of that time into the scenario at which the critical action was made.
      OUTCOME: Project participants were 35 nurses divided into 10 simulation groups. A
      paired-samples Student t test demonstrated that the group mean pretest score of
      56.5% (SD, 17%) increased to 84.6% (SD, 10%), a significant increase of 27.9% (P
      < .0001). In the scenarios, participants decreased the time to application of the
      first correct critical intervention from 37% in scenario 1 to 25% in scenario 2,
      and the time to escalate care decreased from 66% of scenario time to 61%.
      CONCLUSION: Use of e-learning, simulation with organized debriefing, and SBAR
      communication can improve instability recognition and communication resulting in
      improved knowledge and decreased time to critical actions.

PMID- 25856035
TI  - Comparison of 3 methods to prevent pain and bruising after subcutaneous heparin
      administration.
AB  - PURPOSE: The purpose of this study was to assess the effects of the injection
      duration (30 seconds) and local dry cold application (5 minutes before and after
      injection) on pain intensity and bruising at the injection site in subcutaneous
      heparin injections. DESIGN: This was a randomized controlled, prospective,
      experimental study. SETTING: This study was performed between February 2011 and
      February 2012 in the orthopedic wards of 1 university hospital. SAMPLE: The
      sample consisted of 60 patients receiving subcutaneous injections of heparin once
      a day and hospitalized in the orthopedic and trauma wards. METHODS: A
      computerized randomization program was used to allocate the patients to 3
      experimental groups: group A (30-second injection duration), group B (30-second
      injection duration and 5-minute dry cold application applied locally), and group
      C (injection administered for 10 seconds and no dry cold application applied
      locally). RESULTS: This study observed statistically significant differences in
      pain intensity and bruising occurrence and formation measured over time among
      groups A and B (30-second injection duration or 30-second injection duration and
      5-minute local dry cold application) and group C (10-second injection duration).
      CONCLUSION: It was determined that a subcutaneous injection duration of 30
      seconds and 5-minute local dry cold application (before and after injection) can
      be effective in decreasing the intensity of pain and in reducing the occurrence
      of bruising.

PMID- 25856036
TI  - Clinical practice in CNS education: there's an app for that!: Part 2: apps for
      general reference, specialty practice, and patient education.

PMID- 25856037
TI  - Clinical nurse specialist profile.

PMID- 25856039
TI  - Breast self-examination education for BRCA mutation carriers by clinical nurse
      specialists.
AB  - PURPOSE: Breast self-examination (BSE) may be beneficial for women with a BRCA1
      or BRCA2 mutation. Therefore, these women are often advised to perform BSE.
      However, only 20% to 35% is performing BSE monthly, and proficiency levels are
      low. Recently diagnosed carriers are educated by a specially trained clinical
      nurse specialist (CNS) on how to perform BSE, as part of the yearly surveillance.
      Clinical nurse specialists are already commonly involved in breast cancer care.
      However, CNSs are not yet involved in the counseling of BRCA mutation carriers.
      The aim of this RCT was 2-fold: (1) to evaluate the feasibility of CNS-led BSE
      education (based on the Health Belief Model) as part of BRCA surveillance and (2)
      to evaluate the effects and feasibility of additional written information
      leaflets concerning BSE. METHODS: Thirty-seven female BRCA1 or BRCA2 mutation
      carriers were randomized into the intervention or control group. Women in both
      groups were educated about BSE by a specially trained CNS during the yearly visit
      to the outpatient clinic. The intervention group received additional written BSE
      instructions. After 3 months, 29 patients filled out a questionnaire, covering
      demographic characteristics, BSE behavior, and patient satisfaction. RESULTS: The
      BSE frequencies did not significantly differ between both groups. A significant
      increase in the self-reported frequency of BSE after CNS-led education (P < .001)
      was shown. Before the education, the main reason for not performing BSE was that
      women had felt unable to perform BSE (42.9%). Patient satisfaction with the CNS
      led education was high. CONCLUSION: CNS-led BSE education is feasible for the
      yearly breast surveillance of BRCA mutation carriers. In addition, a leaflet was
      shown to be useful as an additional source of information for patients.
      IMPLICATIONS: These results indicate that it is feasible to involve a CNS in the
      yearly surveillance of BRCA mutation carriers, which could be a solution for the
      continuous increased demand for care, while providing continuing high-quality
      care.

PMID- 25856041
TI  - Raising a child with special needs: the perspective of caregivers.
AB  - PURPOSE: Among Canadian children 14 years or younger, an estimated 202 350 (3.7%)
      are currently diagnosed with a disability. Because of the amount of care and
      attention children with disabilities require, parents of these children may also
      experience tribulations. For the sake of this article, tribulations refer to
      difficulties. Therefore, the purpose of this research was to examine the lived
      experiences of caregivers of children with disabilities. DESIGN: A qualitative
      approach, more specifically phenomenology, was utilized to guide this research.
      SAMPLE: Eight participants (5 biological mothers, 2 adoptive mothers, and 1
      father) were recruited from a facility in Southern Ontario that serves children
      with physical and developmental disabilities. METHODS: Background questionnaires
      were completed, and 1-on-1 semistructured interviews were conducted with 8
      caregivers of children with disabilities. RESULTS: The following themes emerged:
      (1) life as a caregiver, (2) impact on siblings as perceived by the parents, and
      (3) changes as a result of having a child with disabilities. This article
      addresses only the theme "life as a caregiver." CONCLUSION: Overall, the research
      study revealed the lived experiences of raising a child with special needs by
      specifically focusing on the lives of caregivers. Despite the many difficulties
      encountered, caregivers identified positive aspects associated with raising a
      child with special needs and the coping mechanisms that assist them in managing
      their stressors. IMPLICATIONS: This research study provides valuable information
      regarding the lived experiences of caregivers of children with special needs. It
      may assist other individuals in similar situations by providing comfort knowing
      that they are not the only ones encountering this journey. It may also allow them
      to look at their life story with a more positive outlook. It can offer these
      individuals with coping mechanisms that may assist them in dealing with their
      stresses. Lastly, it contributes to research that examines the lives of
      caregivers of children with disabilities by relying on the voice of the
      caregivers.

PMID- 25856042
TI  - Wheelchair ergonomic hand drive mechanism use improves wrist mechanics associated
      with carpal tunnel syndrome.
AB  - Among conventional manual wheelchair (CMW) users, 49% to 63% experience carpal
      tunnel syndrome (CTS) that is likely induced by large forces transmitted through
      the wrist and extreme wrist orientations. The ergonomic hand drive mechanism
      (EHDM) tested in this study has been shown to utilize a more neutral wrist
      orientation. This study evaluates the use of an EHDM in terms of wrist
      orientations that may predispose individuals to CTS. Eleven adult full-time CMW
      users with spinal cord injury participated. Motion data were captured as
      participants propelled across a flat surface, completing five trials in a CMW and
      five trials in the same CMW fitted with the EHDM. Average angular wrist
      orientations were compared between the two propulsion styles. Use of the EHDM
      resulted in reduced wrist extension and ulnar deviation. The shift to more
      neutral wrist orientations observed with EHDM use may reduce median nerve
      compression. 

PMID- 25856043
TI  - The role of bio-inspired hierarchical structures in wetting.
AB  - Superhydrophobicity facilitates the development of self-cleaning, anti
      biofouling, and anti-corrosion surfaces. The leaves of the lotus (Nelumbo
      nucifera) and taro (Colocasia esculenta) plants are well known for their self
      cleaning properties. A hierarchical structure comprising papillae epidermal cells
      superimposed with epicuticular wax crystalloids of varying shapes, sizes, and
      orientations is an important aspect of the surface of these plant leaves. We
      fabricated two types of hierarchical structures biomimicking the surface
      topography of the lotus leaf. The hierarchical patterns successfully demonstrated
      the superhydrophobic state in comparison with nano and micro patterns. We used
      the finite element method (FEM) to simulate and understand the wetting process.
      The FEM simulations showed good correlation with the experimental results. FEM
      was helpful in understanding the wetting of enormously complex biological
      surfaces with relative ease, and it qualifies as a potential tool for designing
      superhydrophobic surfaces. Using the FEM framework, we further designed surfaces
      to optimize the order of the shapes in hierarchy. The results showed that the
      superhydrophobic surface with the lowest wetted area was obtained by placing
      shapes with smaller geometric angles at the top of the hierarchy. This
      arrangement of shapes provides the optimum combination of superhydrophobicity and
      surface integrity. This observation explains why the hierarchical structure of
      many superhydrophobic leaves follows this order. We also investigated the complex
      hierarchical structure of Salvinia minima. Owing to its remarkable ability to
      entrap air and pin the contact line, it exhibits superhydrophobicity along with
      the much-required Cassie state. These properties of Salvinia minima make it an
      excellent candidate for developing omniphobic surfaces. 

PMID- 25856044
TI  - Confocal Laser Scanning Microscopy Analysis of 10 Cases of Craniofacial Fibrous
      Dysplasia.
AB  - Fibro-osseous lesions (FOL) represent a heterogeneous group of lesions that
      exhibit a variety of clinic-pathological features. Recently, based on the new
      World Health Organization classification system, these lesions were reclassified
      as follows: (1) fibrous dysplasia (FD), (2) osseous dysplasia, and (3) ossifying
      fibroma. Nevertheless, the nosologic placement of FOL may be problematic because
      of substantial overlap in the histopathological findings. In this study, we
      analyzed 10 cases of FD by both optical and confocal laser scanning microscopy, a
      research technique based on the laser light microscopic analysis of stained
      biological samples that allows improved tissue imaging and bidimensional pictures
      with high resolution at the cellular level to provide a better understanding of
      the diagnosis of this disease. 

PMID- 25856045
TI  - Continuous intraperitoneal insulin infusion versus subcutaneous insulin therapy
      in the treatment of type 1 diabetes: effects on glycemic variability.
AB  - INTRODUCTION: As continuous intraperitoneal insulin infusion (CIPII) results in a
      more physiologic action of insulin than subcutaneous (SC) insulin administration,
      we hypothesized that CIPII would result in less glycemic variability (GV) than SC
      insulin therapy among type 1 diabetes mellitus (T1DM) patients. MATERIALS AND
      METHODS: Data from 5-day blind continuous glucose monitoring (CGM) measurements
      performed during a 26-week, prospective, observational case-control study were
      analyzed. The coefficient of variation (CV) was the primary measure of GV. In
      addition, the SD of the mean glucose level, mean of daily differences, and mean
      amplitude of glycemic excursions were calculated. RESULTS: In total, 176 patients
      (36% male; mean age, 49 [SD 13] years; median diabetes duration, 24
      [interquartile range, 17, 35] years; glycated hemoglobin level, 63 [10]
      mmol/mmol), of which 37 used CIPII and 139 SC insulin therapy, were analyzed. CGM
      data were available for 169 patients at baseline (CIPII, n=35; SC, n=134) and for
      164 patients at 26 weeks (CIPII, n=35; SC, n=129). After adjustment for baseline
      differences, the CV was 4.9% (95% confidence interval, 1.0, 8.8) lower with CIPII
      compared with SC-treated patients, irrespective of the use of multiple daily
      injections or continuous SC insulin infusion. There were no differences in other
      indices of GV between groups. CONCLUSIONS: Despite higher blood glucose, the CV
      was slightly lower with CIPII compared with SC insulin therapy in T1DM patients,
      and other measures of GV were identical. Future studies are needed to confirm
      these findings and investigate whether this results in prevention of hypoglycemia
      and even perhaps (less) microvascular complications.

PMID- 25856047
TI  - Editorial comment on Journal of the American Dental Association article,
      "Outcomes of implants and restorations placed in general dental practices: a
      retrospective study by the Practitioners Engaged in Applied Research and Learning
      (PEARL) Network".

PMID- 25856048
TI  - Outcomes of general dentists performing surgical and prosthetic implant
      treatment.

PMID- 25856049
TI  - Effects of nonsteroidal anti-inflammatory drugs on osseointegration: a review.
AB  - The purpose of this study was to review the effects of nonsteroidal anti
      inflammatory drugs on osseointegration and determine whether they cause failures
      in dental implants and whether patients who use them chronically can receive
      dental implants safely. A bibliographic electronic search was performed using the
      Cochrane Library, PubMed, and Medline databases, selecting articles published
      between January 1982 and December 2012. The search included the following
      keywords, either alone or combined: "nonsteroidal anti-inflammatory drugs,"
      "dental implants," "bone healing," and "osteoprogenitor cells." The inclusion
      criteria were the following: randomized, double-blind, placebo-controlled
      clinical studies, in vivo animal model studies of osseointegration, and in vitro
      studies of the effects of these agents on osteoprogenitor cells. The literature
      search revealed 360 references. A total of 31 articles met the inclusion
      criteria, including 2 clinical trials, 20 animal studies, and 9 osteoprogenitor
      cell studies. The clinical trials revealed that cyclooxygenase-1 (COX-1)
      inhibitors did not impair osseointegration. The animal studies showed that any
      drug that is capable of inhibiting COX-2 may impair the osseointegration process.
      The in vitro studies showed that COX-2 inhibitors are the most potent depressors
      of osseointegration at the cellular level. Caution must be taken when selecting
      COX-2 nonsteroidal anti-inflammatory drugs during the postoperative period. 

PMID- 25856050
TI  - Predictors of Indoor Radon Concentrations in Pennsylvania, 1989-2013.
AB  - BACKGROUND: Radon is the second-leading cause of lung cancer worldwide. Most
      indoor exposure occurs by diffusion of soil gas. Radon is also found in well
      water, natural gas, and ambient air. Pennsylvania has high indoor radon
      concentrations; buildings are often tested during real estate transactions, with
      results reported to the Department of Environmental Protection (PADEP).
      OBJECTIVES: We evaluated predictors of indoor radon concentrations. METHODS:
      Using first-floor and basement indoor radon results reported to the PADEP between
      1987 and 2013, we evaluated associations of radon concentrations (natural log
      transformed) with geology, water source, building characteristics, season,
      weather, community socioeconomic status, community type, and unconventional
      natural gas development measures based on drilled and producing wells. RESULTS:
      Primary analysis included 866,735 first measurements by building, with the large
      majority from homes. The geologic rock layer on which the building sat was
      strongly associated with radon concentration (e.g., Axemann Formation, median =
      365 Bq/m3, IQR = 167-679 vs. Stockton Formation, median = 93 Bq/m3, IQR = 52
      178). In adjusted analysis, buildings using well water had 21% higher
      concentrations (beta = 0.191, 95% CI: 0.184, 0.198). Buildings in cities (vs.
      townships) had lower concentrations (beta = -0.323, 95% CI: -0.333, -0.314). When
      we included multiple tests per building, concentrations declined with repeated
      measurements over time. Between 2005 and 2013, 7,469 unconventional wells were
      drilled in Pennsylvania. Basement radon concentrations fluctuated between 1987
      and 2003, but began an upward trend from 2004 to 2012 in all county categories (p
      < 0.001), with higher levels in counties having >= 100 drilled wells versus
      counties with none, and with highest levels in the Reading Prong. CONCLUSIONS:
      Geologic unit, well water, community, weather, and unconventional natural gas
      development were associated with indoor radon concentrations. Future studies
      should include direct environmental measurement of radon, as well as building
      features unavailable for this analysis. CITATION: Casey JA, Ogburn EL, Rasmussen
      SG, Irving JK, Pollak J, Locke PA, Schwartz BS. 2015. Predictors of indoor radon
      concentrations in Pennsylvania, 1989-2013. Environ Health Perspect 123:1130-1137;
      http://dx.doi.org/10.1289/ehp.1409014.

PMID- 25856052
TI  - New and emerging therapeutic options for the management of chemotherapy-induced
      nausea and vomiting.
AB  - Chemotherapy-induced nausea and vomiting (CINV) remains one of the most
      challenging adverse events of chemotherapy, and one that has substantial negative
      effects on patients, clinicians, and the wider health care system. Use of CINV
      prophylaxis consistent with clinical practice guidelines is essential for
      attaining optimal CINV control. In recent years, there has been a dramatic
      improvement in the control of CINV with the introduction of effective antiemetic
      agents, including the serotonin (5-hydroxytryptamine [5-HT3]) receptor
      antagonists (ondansetron, granisetron, and palonosetron) and the neurokinin-1
      (NK1) receptor antagonists (aprepitant and fosaprepitant). An important benefit
      of the newer antiemetic agents is their improved ability to control the delayed
      CINV that can develop in the days after chemotherapy administration. In October
      2014, a fixed-dose oral combination containing the novel NK1 receptor antagonist
      netupitant and palonosetron (NEPA) received approval from the US Food and Drug
      Administration. The combination of 2 effective antiemetic agents in a single,
      oral capsule may help simplify CINV management. Ongoing studies are evaluating
      new CINV approaches (eg, the novel NK1 receptor antagonist rolapitant), as well
      as the optimal use of existing therapies. Patient education regarding the timing,
      prevention, and treatment of CINV is another key component of CINV management.

PMID- 25856051
TI  - Food and Nutrient Intake in African American Children and Adolescents Aged 5 to
      16 Years in Baltimore City.
AB  - OBJECTIVE: This study aimed to describe food and nutrient intake for low-income,
      urban African American children and adolescents, to highlight the need for
      further nutrition intervention programs and appropriate tools to address
      overweight and obesity. METHODS: This was a cross-sectional study using
      interviewer-administered single 24-hour dietary recalls. Participants were low
      income African American boys and girls aged 5-16 years or their caregivers in
      Baltimore City. Frequency of food consumption and dietary intakes were analyzed
      by gender and age groups. RESULTS: Eighty-one participants were included for
      analysis. Mean daily energy intakes exceeded Dietary Reference Intakes (DRIs)
      from 10% to 71% across all gender-age groups: 2304 kcal for children aged 5-8
      years; 2429 kcal and 2732 kcal for boys and girls aged 9-13 years, respectively;
      and 3339 kcal and 2846 kcal for boys and girls aged 14-16 years, respectively.
      The most frequently reported consumed foods were sweetened drinks, chips,
      candies, and milk across all age groups. The majority of participants (79-100%)
      did not meet the DRIs for dietary fiber and vitamin E across all gender-age
      groups. Milk accounted for 14%, 17%, and 21% of energy, fat, and protein intake,
      respectively, among children 5-8 years of age, while pizza was the top source of
      energy, fat, and protein (11%, 13%, and 18%, respectively) among 14-to 16-year
      old adolescents. Sweetened drinks and sweetened juices were major sources of
      sugar, contributing 33% for 5-8 year olds, 29% for 9-13 year olds, and 35% for 14
      16 year olds. CONCLUSIONS: Mean daily energy intake exceeded dietary
      recommendations across all gender-age groups. This study has provided previously
      unavailable information on diet and highlights foods to be targeted in nutrition
      intervention programs.

PMID- 25856056
TI  - Muscle-Activation Onset Times With Shoes and Foot Orthoses in Participants With
      Chronic Ankle Instability.
AB  - CONTEXT: Participants with chronic ankle instability (CAI) use an altered
      neuromuscular strategy to shift weight from double-legged to single-legged
      stance. Shoes and foot orthoses may influence these muscle-activation patterns.
      OBJECTIVE: To evaluate the influence of shoes and foot orthoses on onset times of
      lower extremity muscle activity in participants with CAI during the transition
      from double-legged to single-legged stance. DESIGN: Cross-sectional study.
      SETTING: Musculoskeletal laboratory. PATIENTS OR OTHER PARTICIPANTS: A total of
      15 people (9 men, 6 women; age = 21.8 +/- 3.0 years, height = 177.7 +/- 9.6 cm,
      mass = 72.0 +/- 14.6 kg) who had CAI and wore foot orthoses were recruited.
      INTERVENTION(S): A transition task from double-legged to single-legged stance was
      performed with eyes open and with eyes closed. Both limbs were tested in 4
      experimental conditions: (1) barefoot (BF), (2) shoes only, (3) shoes with
      standard foot orthoses, and (4) shoes with custom foot orthoses (SCFO). MAIN
      OUTCOME MEASURE(S): The onset of activity of 9 lower extremity muscles was
      recorded using surface electromyography and a single force plate. RESULTS: Based
      on a full-factorial (condition, region, limb, vision) linear model for repeated
      measures, we found a condition effect (F(3,91.8) = 9.39, P < .001). Differences
      among experimental conditions did not depend on limb or vision condition. Based
      on a 2-way (condition, muscle) linear model within each region (ankle, knee,
      hip), earlier muscle-activation onset times were observed in the SCFO than in the
      BF condition for the peroneus longus (P < .001), tibialis anterior (P = .003),
      vastus medialis obliquus (P = .04), and vastus lateralis (P = .005). Furthermore,
      the peroneus longus was activated earlier in the shoes-only (P = .02) and shoes
      with-standard-foot-orthoses (P = .03) conditions than in the BF condition. No
      differences were observed for the hip muscles. CONCLUSIONS: Earlier onset of
      muscle activity was most apparent in the SCFO condition for ankle and knee
      muscles but not for hip muscles during the transition from double-legged to
      single-legged stance. These findings might help clinicians understand how shoes
      and foot orthoses can influence neuromuscular control in participants with CAI.

PMID- 25856057
TI  - Widening and diversifying the proteome capture by combinatorial peptide ligand
      libraries via Alcian Blue dye binding.
AB  - Combinatorial peptide ligand libraries (CPLLs) tend to bind complex molecules
      such as dyes due to their aromatic, heterocyclic, hydrophobic, and ionic nature
      that may affect the protein capture specificity. In this experimental work Alcian
      Blue 8GX, a positively charged phthalocyanine dye well-known to bind to
      glycoproteins and to glucosaminoglycans, was adsorbed on a chemically modified
      CPLL solid phase, and the behavior of the resulting conjugate was then
      investigated. The control and dye-adsorbed beads were used to harvest the human
      urinary proteome at physiological pH, this resulting in a grand total of 1151
      gene products identified after the capture. Although the Alcian Blue-modified
      CPLL incremented the total protein capture by 115 species, it particularly
      enriched some families among the harvested proteins, such as glycoproteins and
      nucleotide-binding proteins. This study teaches that it is possible, via the two
      combined harvest mechanisms, to drive the CPLL capture toward the enrichment of
      specific protein categories. 

PMID- 25856058
TI  - Development and characterization of polymorphic genic-SSR markers in Larix
      kaempferi.
AB  - New simple sequence repeat (SSR) markers were developed in the Japanese larch
      (Larix kaempferi) using unigene sequences for further genetic diversity studies
      and the genetic improvement of breeding programs. One thousand two handred and
      thirty five (1235) primer pairs were tested and 165 successfully identified in L.
      kaempferi. Out of the amplified candidate markers, 145 (90.6%) exhibited
      polymorphism among 24 individuals of L. kaempferi, with the number of alleles per
      locus (Na), observed heterozygosity (Ho), expected heterozygosity (He) and
      polymorphic information content (PIC) averaging at 4.510, 0.487, 0.518 and 0.459,
      respectively. Cross-species amplification of randomly selection of 30 genic-SSRs
      among the 145 polymorphic ones showed that 80.0% of the SSRs could be amplified
      in Larix olgensis, 86.7% could be amplified in Larix principi-rupprechtii and
      83.0% could be amplified in Larix gmelinii. High rates of cross-species
      amplification were observed. The genic-SSRs developed herein would be a valuable
      resource for genetic analysis of Larix kaempferi and related species, and also
      have the potential to facilitate the genetic improvement and breeding of larch. 

PMID- 25856060
TI  - Various extraction methods for obtaining stilbenes from grape cane of Vitis
      vinifera L.
AB  - Grape cane, leaves and grape marc are waste products from viticulture, which can
      be used to obtain secondary stilbene derivatives with high antioxidant value. The
      presented work compares several extraction methods: maceration at laboratory
      temperature, extraction at elevated temperature, fluidized-bed extraction,
      Soxhlet extraction, microwave-assisted extraction, and accelerated solvent
      extraction. To obtain trans-resveratrol, trans-epsilon-viniferin and r2-viniferin
      from grape cane of the V. vinifera variety Cabernet Moravia, various conditions
      were studied: different solvents, using powdered versus cut cane material,
      different extraction times, and one-step or multiple extractions. The largest
      concentrations found were 6030 +/- 680 ug/g dry weight (d.w.) for trans
      resveratrol, 2260 +/- 90 ug/g d.w. for trans-epsilon-viniferin, and 510 +/- 40
      ug/g d.w. for r2-viniferin. The highest amounts of stilbenes (8500 +/- 1100 ug/g
      d.w.) were obtained using accelerated solvent extraction in methanol. 

PMID- 25856059
TI  - Appropriate first-line regimens to combat Helicobacter pylori antibiotic
      resistance: an Asian perspective.
AB  - Asia has the largest population of any continent and the highest incidence of
      gastric cancer in the world, making it very important in the context of
      Helicobacter pylori infection. According to current guidelines, standard triple
      therapy containing a proton pump inhibitor (PPI) and two antibiotics; amoxicillin
      (AMX) and clarithromycin (CAM) or metronidazole (MNZ), is still the preferred
      first-line regimen for treatment of H. pylori infection. However, the efficacy of
      legacy triple regimens has been seriously challenged, and they are gradually
      becoming ineffective. Moreover, some regions in Asia show patterns of emerging
      antimicrobial resistance. More effective regimens including the bismuth and non
      bismuth quadruple, sequential, and dual-concomitant (hybrid) regimens are now
      replacing standard triple therapies as empirical first-line treatments on the
      basis of the understanding of the local prevalence of H. pylori antimicrobial
      resistance. Selection of PPI metabolized by the non-enzymatic pathway or minimal
      first pass metabolism and/or increasing dose of PPI are important to increase H.
      pylori eradication rates. Therefore, local antibiotic resistance surveillance
      updates, selection of appropriate first-line regimens with non-enzymatic PPI
      and/or increased doses of PPI, and detailed evaluation of patients' prior
      antibiotic usage are all essential information to combat H. pylori antibiotic
      resistance in Asia. 

PMID- 25856061
TI  - Thapsigargin--from Thapsia L. to mipsagargin.
AB  - The sesquiterpene lactone thapsigargin is found in the plant Thapsia garganica
      L., and is one of the major constituents of the roots and fruits of this
      Mediterranean species. In 1978, the first pharmacological effects of thapsigargin
      were established and the full structure was elucidated in 1985. Shortly after,
      the overall mechanism of the Sarco-endoplasmic reticulum Ca2+-ATPase (SERCA)
      inhibition that leads to apoptosis was discovered. Thapsigargin has a potent
      antagonistic effect on the SERCA and is widely used to study Ca2+-signaling. The
      effect on SERCA has also been utilized in the treatment of solid tumors. A
      prodrug has been designed to target the blood vessels of cancer cells; the death
      of these blood vessels then leads to tumor necrosis. The first clinical trials of
      this drug were initiated in 2008, and the potent drug is expected to enter the
      market in the near future under the generic name Mipsagargin (G-202). This review
      will describe the discovery of the new drug, the on-going elucidation of the
      biosynthesis of thapsigargin in the plant and attempts to supply the global
      market with a novel potent anti-cancer drug. 

PMID- 25856062
TI  - Bactericidal effect of extracts and metabolites of Robinia pseudoacacia L. on
      Streptococcus mutans and Porphyromonas gingivalis causing dental plaque and
      periodontal inflammatory diseases.
AB  - The mouth cavity hosts many types of anaerobic bacteria, including Streptococcus
      mutans and Porphyromonas gingivalis, which cause periodontal inflammatory
      diseases and dental caries. The present study was conducted to evaluate the
      antibacterial potential of extracts of Robinia pseudoacacia and its different
      fractions, as well as some of its natural compounds against oral pathogens and a
      nonpathogenic reference bacteria, Escherichia coli. The antibacterial activity of
      the crude extract and the solvent fractions (hexane, chloroform, ethyl acetate
      and butanol) of R. pseudoacacia were evaluated against S. mutans, P. gingivalis
      and E. coli DH5alpha by standard micro-assay procedure using conventional sterile
      polystyrene microplates. The results showed that the crude extract was more
      active against P. gingivalis (100% growth inhibition) than against S. mutans (73%
      growth inhibition) at 1.8 mg/mL. The chloroform and hexane fractions were active
      against P. gingivalis, with 91 and 97% growth inhibition, respectively, at 0.2
      mg/mL. None of seven natural compounds found in R. pseudoacacia exerted an
      antibacterial effect on P. gingivalis; however, fisetin and myricetin at 8 ug/mL
      inhibited the growth of S. mutans by 81% and 86%, respectively. The crude extract
      of R. pseudoacacia possesses bioactive compounds that could completely control
      the growth of P. gingivalis. The antibiotic activities of the hexane and
      chloroform fractions suggest that the active compounds are hydrophobic in nature.
      The results indicate the effectiveness of the plant in clinical applications for
      the treatment of dental plaque and periodontal inflammatory diseases and its
      potential use as disinfectant for various surgical and orthodontic appliances. 

PMID- 25856063
TI  - Synthesis of novel perfluoroalkylglucosides on zeolite and non-zeolite catalysts.
AB  - Perfluoroalkylglucosides comprise a very important class of fluorine-containing
      surfactants. These compounds can be synthesized by using the Fisher reaction,
      starting directly from glucose and the required perfluoroalcohols. We wish to
      report on the use of zeolite catalysts of different structure and composition for
      the synthesis of perfluoroalkylglucosides when using glucose and 1
      octafluoropentanol as substrates. Zeolites of different pore architecture have
      been chosen (ZSM-5, ZSM-12, MCM-22 and Beta). Zeolites were characterized by XRD,
      nitrogen sorption, scanning electron microscopy (SEM) and solid-state 27Al MAS
      NMR spectroscopy. The activity of the zeolite catalysts in the glycosidation
      reaction was studied in a batch reactor at 100  degrees C below atmospheric
      pressure. The performance of zeolites was compared to other catalysts, an ion
      exchange resin (Purolite) and a montmorillonite-type layered aluminosilicate. The
      catalytic performance of zeolite Beta was the highest among the zeolites studied
      and the results were comparable to those obtained over Purolite and
      montmorillonite type catalysts. 

PMID- 25856064
TI  - Trans-selective rhodium catalysed conjugate addition of organoboron reagents to
      dihydropyranones.
AB  - The selective synthesis of 2,6-trans-tetrahydropyran derivatives employing the
      rhodium catalysed addition of organoboron reagents to dihydropyranone templates,
      derived from a zinc-catalysed hetero-Diels-Alder reaction, is reported. The
      addition of both arylboronic acids and potassium alkenyltrifluoroborates have
      been accomplished in high yields using commercially-available [Rh(cod)(OH)]2
      catalyst. The selective formation of the 2,6-trans-tetrahydropyran stereoisomer
      is consistent with a mechanism involving alkene association and carbometalation
      on the less hindered face of the dihydropyranone. 

PMID- 25856065
TI  - Measurement of soluble C-type lectin-like receptor 2 in human plasma.
AB  - Detection of platelet activation in vivo is useful to identify patients at risk
      of thrombotic diseases. Platelet factor 4 (PF4) and beta-thromboglobulin (beta
      TG) are used for this purpose; however, they are easily released upon the minimal
      platelet activation that occurs during sampling. Soluble forms of several
      platelet membrane proteins are released upon platelet activation; however, the
      soluble form of C-type lectin-like receptor 2 (sCLEC-2) has not yet been fully
      investigated. Western blotting with an anti-CLEC-2 antibody showed that sCLEC-2
      was released from washed human platelets stimulated with collagen mimetics. To
      detect sCLEC-2 in plasma, we established a sandwich enzyme-linked immunosorbent
      assay (ELISA) using F(ab')2 anti-CLEC-2 monoclonal antibodies. Although plasma
      mixed with citrate, adenosine, theophylline and adenosine (CTAD) is needed for
      the PF4 and beta-TG assays, effects of anti-coagulants (EDTA, citrate and CTAD)
      on the sCLEC-2 ELISA were negligible. Moreover, while special techniques are
      required for blood sampling and sample preparation for PF4 and beta-TG assay, the
      standard blood collections procedures used in daily clinical laboratory tests
      have shown to suffice for sCLEC-2 analysis. In this study, we found that two
      forms of sCLEC-2 are released after platelet activation: a shed fragment and a
      microparticle-bound full-length protein, both of which are detected by the sCLEC
      2 ELISA. The average concentration of sCLEC-2 in the plasma of 10 healthy
      individuals was 97 +/- 55 pg/ml, whereas that in the plasma of 25 patients with
      diabetes mellitus (DM) was 149 +/- 260 pg/ml. A trend towards an increase in
      sCLEC-2 concentration in the DM patients may reflect in vivo platelet activation
      in the patients, suggesting that sCLEC-2 may have clinical significance as a
      biomarker of in vivo platelet activation.

PMID- 25856067
TI  - Ethical problems in ex vivo or cadaver organ transplantation: should the donation
      be paid?
AB  - Financial incentives for organ donation (from living or cadaveric donors) have
      been considered ethically acceptable by some bioethicists, and recently,
      according to the media, by Prof. Gary Becker, Nobel Laureate for Economy.
      However, the only countries to have approved a law allowing financial incentives
      for organ donation are Iran in 1988 and, in some way and much later, Singapore
      and Saudi Arabia. In Europe financial incentives for donors are prohibited,
      except maybe in Austria. In Germany, it is forbidden to purchase organs not only
      in the home country, but all over the world. The author was involved, as peer
      reviewer of a major international Transplant journal, in the evaluation of some
      papers concerning paid kidney living donors in Iran, and therefore made an
      extensive literature search on this topic and more generally on paid kidney
      living donation all over the world. The situation in Italy will also be reported
      and analysed.

PMID- 25856066
TI  - Restoring the Co magnetic moments at interfacial Co-porphyrin arrays by site
      selective uptake of iron.
AB  - Magnetochemistry recently emerged as a promising approach to control addressable
      spin arrays on surfaces. Here we report on the binding, spatial ordering, and
      magnetic properties of Fe on a highly regular Co-tetraphenylporphyrin (Co-TPP)
      template and highlight how the Fe controls the magnetism of the Co centers. As
      evidenced by scanning tunneling microscopy (STM) single Fe atoms attach to the
      saddle-shape conformers site-selectively in a unique coordination environment
      offered through a heptamer defined by the Co-N-C-C-C-N cyclic subunit. While the
      magnetic moment of Co is quenched for bare Co-TPP/Ag(111), the Fe presence
      revives it. Our X-ray magnetic circular dichroism (XMCD) experiments,
      complemented by density functional theory (DFT) calculations, evidence a
      ferromagnetic coupling between the Fe and the Co center concomitant with a
      complex charge redistribution involving the porphyrin ligand. Thus, we
      demonstrate an unusual metalloporphyrin coordination geometry that opens pathways
      to spatially order and engineer magnetic moments in surface-based nanostructures.

PMID- 25856068
TI  - Quality of life in patients with metastatic breast cancer.

PMID- 25856069
TI  - Quality of life in clinical trials of metastatic breast cancer.

PMID- 25856070
TI  - Effective management of quality of life in metastatic breast cancer.

PMID- 25856071
TI  - Effective management of quality of life in metastatic breast cancer: general
      discussion.

PMID- 25856072
TI  - Community-centered responses to Ebola in urban Liberia: the view from below.
AB  - BACKGROUND: The West African Ebola epidemic has demonstrated that the existing
      range of medical and epidemiological responses to emerging disease outbreaks is
      insufficient, especially in post-conflict contexts with exceedingly poor
      healthcare infrastructures. In this context, community-based responses have
      proven vital for containing Ebola virus disease (EVD) and shifting the epidemic
      curve. Despite a surge in interest in local innovations that effectively
      contained the epidemic, the mechanisms for community-based response remain
      unclear. This study provides baseline information on community-based epidemic
      control priorities and identifies innovative local strategies for containing EVD
      in Liberia. METHODOLOGY/PRINCIPAL FINDINGS: This study was conducted in September
      2014 in 15 communities in Monrovia and Montserrado County, Liberia--one of the
      epicenters of the Ebola outbreak. Findings from 15 focus group discussions with
      386 community leaders identified strategies being undertaken and recommendations
      for what a community-based response to Ebola should look like under then-existing
      conditions. Data were collected on the following topics: prevention,
      surveillance, care-giving, community-based treatment and support, networks and
      hotlines, response teams, Ebola treatment units (ETUs) and hospitals, the
      management of corpses, quarantine and isolation, orphans, memorialization, and
      the need for community-based training and education. Findings have been presented
      as community-based strategies and recommendations for (1) prevention, (2)
      treatment and response, and (3) community sequelae and recovery. Several models
      for community-based management of the current Ebola outbreak were proposed.
      Additional findings indicate positive attitudes towards early Ebola survivors,
      and the need for community-based psychosocial support. CONCLUSIONS/SIGNIFICANCE:
      Local communities' strategies and recommendations give insight into how urban
      Liberian communities contained the EVD outbreak while navigating the systemic
      failures of the initial state and international response. Communities in urban
      Liberia adapted to the epidemic using multiple coping strategies. In the absence
      of health, infrastructural and material supports, local people engaged in self
      reliance in order to contain the epidemic at the micro-social level. These
      innovations were regarded as necessary, but as less desirable than a well
      supported health-systems based response; and were seen as involving considerable
      individual, social, and public health costs, including heightened vulnerability
      to infection.

PMID- 25856073
TI  - Prediction of protein structural features from sequence data based on Shannon
      entropy and Kolmogorov complexity.
AB  - While the genome for a given organism stores the information necessary for the
      organism to function and flourish it is the proteins that are encoded by the
      genome that perhaps more than anything else characterize the phenotype for that
      organism. It is therefore not surprising that one of the many approaches to
      understanding and predicting protein folding and properties has come from
      genomics and more specifically from multiple sequence alignments. In this work I
      explore ways in which data derived from sequence alignment data can be used to
      investigate in a predictive way three different aspects of protein structure:
      secondary structures, inter-residue contacts and the dynamics of switching
      between different states of the protein. In particular the use of Kolmogorov
      complexity has identified a novel pathway towards achieving these goals. 

PMID- 25856074
TI  - Investigating male tobacco use and expenditure patterns across socio-economic
      groups in Nigeria.
AB  - The magnitude of variation in economic costs of tobacco consumption among socio
      economic status (SES) groups in Nigeria is unclear. Understanding the factors
      that influence tobacco use and expenditure among different socio-economic groups
      would inform decisions on interventions for tobacco control in Nigeria. Secondary
      data was obtained from the 2008 National demographic and health survey.
      Information on tobacco use and expenditure in households and individual males
      were extracted from the database. A total of 34,070 households and 15,846
      individual males were sampled. Analysis was done using descriptive statistics and
      binary logistic regression analysis. Information on wealth index obtained were
      categorized into socio-economic quintile groups (Q1 to Q5), representing poorest
      to richest socio-economic groups. To estimate expenditure on cigarettes, the
      average cost of a stick of cigarette was obtained and multiplied with the number
      of sticks smoked per day. The proportion of households that use tobacco in
      Nigeria is 5.25% with a greater percentage (89.6%) residing in the rural areas.
      Prevalence of cigarette smoking in individual males is 8.59%, and the poorer SES
      group smoked more cigarettes (20.9%) and spent more (0.60-1.19 USD) than the
      richest SES group. Low education level, traditional beliefs, literacy levels, SES
      and employment status all influence cigarette smoking in adult males. Although
      poor people smoked more and spent more of their income on cigarettes, other
      factors like educational level and traditional beliefs were found to influence
      practice of cigarette smoking in men. This implies that tobacco control
      legislation through increased taxes alone may not effectively reduce the use of
      tobacco and its products in Nigeria. A consolidated approach that includes
      behavioral change procedures, enforcing bans on tobacco advertisement and the use
      of strong graphic anti-tobacco messages targeted at both the poor and rich as
      well as the educated and uneducated need to be effected to reduce tobacco use.

PMID- 25856075
TI  - Prevalence of coronary artery disease evaluated by coronary CT angiography in
      women with mammographically detected breast arterial calcifications.
AB  - To assess the correlation between breast arterial calcifications (BAC) on digital
      mammography and the extent of coronary artery disease (CAD) diagnosed with dual
      source coronary computed tomography angiography (CTA) in a population of women
      both symptomatic and asymptomatic for coronary artery disease. 100 consecutive
      women (aged 34 - 86 years) who underwent both coronary CTA and digital
      mammography were included in the study. Health records were reviewed to determine
      the presence of cardiovascular risk factors such as hypertension, hyperlipidemia,
      diabetes mellitus, and smoking. Digital mammograms were reviewed for the presence
      and degree of BAC, graded in terms of severity and extent. Coronary CTAs were
      reviewed for CAD, graded based on the extent of calcified and non-calcified
      plaque, and the degree of major vessel stenosis. A four point grading scale was
      used for both coronary CTA and mammography. The overall prevalence of positive
      BAC and CAD in the studied population were 12% and 29%, respectively. Ten of the
      12 patients with moderate or advanced BAC on mammography demonstrated moderate to
      severe CAD as determined by coronary CTA. For all women, the positive predictive
      value of BAC for CAD was 0.83 and the negative predictive value was 0.78. The
      presence of BAC on mammography appears to correlate with CAD as determined by
      coronary CTA (Spearman's rank correlation coefficient = 0.48, p<.000001). Using
      logistic regression, the inclusion of BAC as a feature in CAD predication
      significantly increased classification results (p=0.04). 

PMID- 25856076
TI  - GOBLET: the Global Organisation for Bioinformatics Learning, Education and
      Training.
AB  - In recent years, high-throughput technologies have brought big data to the life
      sciences. The march of progress has been rapid, leaving in its wake a demand for
      courses in data analysis, data stewardship, computing fundamentals, etc., a need
      that universities have not yet been able to satisfy--paradoxically, many are
      actually closing "niche" bioinformatics courses at a time of critical need. The
      impact of this is being felt across continents, as many students and early-stage
      researchers are being left without appropriate skills to manage, analyse, and
      interpret their data with confidence. This situation has galvanised a group of
      scientists to address the problems on an international scale. For the first time,
      bioinformatics educators and trainers across the globe have come together to
      address common needs, rising above institutional and international boundaries to
      cooperate in sharing bioinformatics training expertise, experience, and
      resources, aiming to put ad hoc training practices on a more professional footing
      for the benefit of all.

PMID- 25856077
TI  - Chemosensory gene families in adult antennae of Anomala corpulenta Motschulsky
      (Coleoptera: Scarabaeidae: Rutelinae).
AB  - BACKGROUND: The metallic green beetle, Anomala corpulenta (Coleoptera:
      Scarabaeidae: Rutelinae), is a destructive pest in agriculture and horticulture
      throughout Asia, including China. Olfaction plays a crucial role in the survival
      and reproduction of A. corpulenta. As a non-model species, A. corpulenta is
      poorly understood, and information regarding the molecular mechanisms underlying
      olfaction in A. corpulenta and other scarab species is scant.
      METHODOLOGY/PRINCIPLE FINDINGS: We assembled separate antennal transcriptome for
      male and female A. corpulenta using Illumina sequencing technology. The relative
      abundance of transcripts with gene ontology annotations, including those related
      to olfaction in males and females was highly similar. Transcripts encoding 15
      putative odorant binding proteins, five chemosensory proteins, one sensory neuron
      membrane protein, 43 odorant receptors, eight gustatory receptors, and five
      ionotropic receptors were identified. The sequences of all of these chemosensory
      related transcripts were confirmed using reverse transcription polymerase chain
      reaction (RT-PCR), and direct DNA sequencing. The expression patterns of 54
      putative chemosensory genes were analyzed using quantitative real time RT-PCR
      (qRT-PCR). Antenna-specific expression was detected for many of these genes,
      suggesting that they may have important functions in semiochemical detection.
      CONCLUSIONS: The identification of a large number of chemosensory proteins
      provides a major resource for the study of the molecular mechanism of odorant
      detection in A. corpulenta and its chemical ecology. The genes identified,
      especially those that were expressed at high levels in the antennae may represent
      novel molecular targets for the development of population control strategies
      based on the manipulation of chemoreception-driven behaviors.

PMID- 25856078
TI  - Dexamethasone as adjuvant to bupivacaine prolongs the duration of thermal
      antinociception and prevents bupivacaine-induced rebound hyperalgesia via
      regional mechanism in a mouse sciatic nerve block model.
AB  - BACKGROUND: Dexamethasone has been studied as an effective adjuvant to prolong
      the analgesia duration of local anesthetics in peripheral nerve block. However,
      the route of action for dexamethasone and its potential neurotoxicity are still
      unclear. METHODS: A mouse sciatic nerve block model was used. The sciatic nerve
      was injected with 60ul of combinations of various medications, including
      dexamethasone and/or bupivacaine. Neurobehavioral changes were observed for 2
      days prior to injection, and then continuously for up to 7 days after injection.
      In addition, the sciatic nerves were harvested at either 2 days or 7 days after
      injection. Toluidine blue dyeing and immunohistochemistry test were performed to
      study the short-term and long-term histopathological changes of the sciatic
      nerves. There were six study groups: normal saline control, bupivacaine (10mg/kg)
      only, dexamethasone (0.5mg/kg) only, bupivacaine (10mg/kg) combined with low-dose
      (0.14mg/kg) dexamethasone, bupivacaine (10mg/kg) combined with high-dose
      (0.5mg/kg) dexamethasone, and bupivacaine (10mg/kg) combined with intramuscular
      dexamethasone (0.5mg/kg). RESULTS: High-dose perineural dexamethasone, but not
      systemic dexamethasone, combined with bupivacaine prolonged the duration of both
      sensory and motor block of mouse sciatic nerve. There was no significant
      difference on the onset time of the sciatic nerve block. There was "rebound
      hyperalgesia" to thermal stimulus after the resolution of plain bupivacaine
      sciatic nerve block. Interestingly, both low and high dose perineural
      dexamethasone prevented bupivacaine-induced hyperalgesia. There was an early
      phase of axon degeneration and Schwann cell response as represented by S-100
      expression as well as the percentage of demyelinated axon and nucleus in the
      plain bupivacaine group compared with the bupivacaine plus dexamethasone groups
      on post-injection day 2, which resolved on post-injection day 7. Furthermore, we
      demonstrated that perineural dexamethasone, but not systemic dexamethasone, could
      prevent axon degeneration and demyelination. There was no significant caspase
      dependent apoptosis process in the mouse sciatic nerve among all study groups
      during our study period. CONCLUSIONS: Perineural, not systemic, dexamethasone
      added to a clinical concentration of bupivacaine may not only prolong the
      duration of sensory and motor blockade of sciatic nerve, but also prevent the
      bupivacaine-induced reversible neurotoxicity and short-term "rebound
      hyperalgesia" after the resolution of nerve block.

PMID- 25856079
TI  - The impact of resource availability on bacterial resistance to phages in soil.
AB  - Resource availability can affect the coevolutionary dynamics between host and
      parasites, shaping communities and hence ecosystem function. A key finding from
      theoretical and in vitro studies is that host resistance evolves to greater
      levels with increased resources, but the relevance to natural communities is less
      clear. We took two complementary approaches to investigate the effect of resource
      availability on the evolution of bacterial resistance to phages in soil. First,
      we measured the resistance and infectivity of natural communities of soil
      bacteria and phage in the presence and absence of nutrient-providing plants.
      Second, we followed the real-time coevolution between defined bacteria and phage
      populations with resource availability manipulated by the addition or not of an
      artificial plant root exudate. Increased resource availability resulted in
      increases in bacterial resistance to phages, but without a concomitant increase
      in phage infectivity. These results suggest that phages may have a reduced impact
      on the control of bacterial densities and community composition in stable, high
      resource environments. 

PMID- 25856080
TI  - Oral administered particulate yeast-derived glucan promotes hepatitis B virus
      clearance in a hydrodynamic injection mouse model.
AB  - Hepatitis B virus (HBV) persistent infection is associated with ineffective
      immune response for the clearance of virus. Immunomodulators represent an
      important class of therapeutics, which potentially could be beneficial for the
      treatment of HBV infection. The particulate yeast-derived glucan (PYDG) has been
      shown to enhance the innate and adaptive immune responses. We therefore, assessed
      the efficacy of PYDG in enhancing HBV specific immune responses by employing the
      hydrodynamic injection-based (HDI) HBV transfection mouse model. Mice were
      intragatric administered PYDG daily for 9 weeks post pAAV/HBV1.2 hydrodynamic
      injection. PYDG treatment significantly promoted HBV DNA clearance and production
      of HBsAb compared to control mice. PYDG treatment resulted in recruitment of
      macrophages, dendritic cells (DCs) and effector T cells to the liver
      microenvironment, accompanied by a significantly augmented DCs maturation and HBV
      specific IFN-gamma and TNF-alpha production by T cell. In addition, enhanced
      production of Th1 cytokines in liver tissue interstitial fluid (TIF) was
      associated with PYDG administration. Live imaging showed the accumulation of PYDG
      in the mouse liver. Our results demonstrate that PYDG treatment significantly
      enhances HBV-specific Th1 immune responses, accompanied by clearance of HBV DNA,
      and therefore holds promise for further development of therapeutics against
      chronic hepatitis B. 

PMID- 25856081
TI  - Nano-mole scale side-chain signal assignment by 1H-detected protein solid-state
      NMR by ultra-fast magic-angle spinning and stereo-array isotope labeling.
AB  - We present a general approach in 1H-detected 13C solid-state NMR (SSNMR) for side
      chain signal assignments of 10-50 nmol quantities of proteins using a combination
      of a high magnetic field, ultra-fast magic-angle spinning (MAS) at ~80 kHz, and
      stereo-array-isotope-labeled (SAIL) proteins [Kainosho M. et al., Nature 440, 52
      57, 2006]. First, we demonstrate that 1H indirect detection improves the
      sensitivity and resolution of 13C SSNMR of SAIL proteins for side-chain
      assignments in the ultra-fast MAS condition. 1H-detected SSNMR was performed for
      micro-crystalline ubiquitin (~55 nmol or ~0.5mg) that was SAIL-labeled at seven
      isoleucine (Ile) residues. Sensitivity was dramatically improved by 1H-detected
      2D 1H/13C SSNMR by factors of 5.4-9.7 and 2.1-5.0, respectively, over 13C
      detected 2D 1H/13C SSNMR and 1D 13C CPMAS, demonstrating that 2D 1H-detected
      SSNMR offers not only additional resolution but also sensitivity advantage over
      1D 13C detection for the first time. High 1H resolution for the SAIL-labeled side
      chain residues offered reasonable resolution even in the 2D data. A 1H-detected
      3D 13C/13C/1H experiment on SAIL-ubiquitin provided nearly complete 1H and 13C
      assignments for seven Ile residues only within ~2.5 h. The results demonstrate
      the feasibility of side-chain signal assignment in this approach for as little as
      10 nmol of a protein sample within ~3 days. The approach is likely applicable to
      a variety of proteins of biological interest without any requirements of highly
      efficient protein expression systems. 

PMID- 25856082
TI  - Genetic diversity and host alternation of the egg parasitoid Ooencyrtus
      pityocampae between the pine processionary moth and the caper bug.
AB  - The increased use of molecular tools for species identification in recent decades
      revealed that each of many apparently generalist parasitoids are actually a
      complex of morphologically similar congeners, most of which have a rather narrow
      host range. Ooencyrtus pityocampae (OP), an important egg parasitoid of the pine
      processionary moth (PPM), is considered a generalist parasitoid. OP emerges from
      PPM eggs after winter hibernation, mainly in spring and early summer, long before
      the eggs of the next PPM generation occurs. The occurrence of OP in eggs of the
      variegated caper bug (CB) Stenozygum coloratum in spring and summer suggests that
      OP populations alternate seasonally between PPM and CB. However, the identity of
      OP population on CB eggs seemed uncertain; unlike OP-PPM populations, the former
      displayed apparently high male/female ratios and lack of attraction to the PPM
      sex pheromone. We studied the molecular identities of the two populations since
      the morphological identification of the genus Ooencyrtus, and OP in particular,
      is difficult. Sequencing of COI and ITS2 DNA fragments and AFLP analysis of
      individuals from both hosts revealed no apparent differences between the OP-PPM
      and the OP-CB populations for both the Israeli and the Turkish OPs, which
      therefore supported the possibility of host alternation. Sequencing data extended
      our knowledge of the genetic structure of OP populations in the Mediterranean
      area, and revealed clear separation between East and West Mediterranean
      populations. The overall level of genetic diversity was rather small, with the
      Israeli population much less diverse than all others; possible explanations for
      this finding are discussed. The findings support the possibility of utilizing the
      CB and other hosts for enhancing biological control of the PPM. 

PMID- 25856084
TI  - Molecular mechanism of calcium-induced adsorption of DNA on zwitterionic
      phospholipid membranes.
AB  - Interaction of DNA with zwitterionic phospholipids is an important long-standing
      problem in the field of liposome-based gene delivery. Although it is well
      established that divalent cations can promote formation of stable DNA
      phospholipid complexes, the underlying molecular mechanism remains largely
      unknown. Here we employ computer simulations to gain atomistically resolved
      insight into the kinetics of calcium-induced adsorption of DNA on zwitterionic
      phosphatidylcholine membranes as well as into the structure and stability of the
      resulting complexes. Overall, our findings show that calcium ions play a dual
      role in DNA-phospholipid systems. First, binding of divalent cations to the lipid
      water interface turns the surface of the zwitterionic membrane positively
      charged, promoting thereby the initial electrostatic attraction of a polyanionic
      DNA molecule. Second, we show that calcium ions are crucial for stabilizing the
      DNA-lipid membrane complex as they bridge together phosphate groups of DNA and
      lipid molecules. In contrast to previous hypotheses, we demonstrate that direct
      interactions between choline groups of phospholipids and DNA phosphates play only
      a rudimentary role as they are relatively short-lived and unstable: typical
      residence times for such interactions are 2 orders of magnitude smaller than
      those for Ca-mediated bridges between DNA and lipid phosphate groups. The results
      of our study can serve as a basis for a deeper understanding of molecular
      mechanisms behind noncovalent binding of DNA and DNA-based nanodevices to complex
      surfaces such as cell membranes. 

PMID- 25856085
TI  - Pulse transit time measured by photoplethysmography improves the accuracy of
      heart rate as a surrogate measure of cardiac output, stroke volume and oxygen
      uptake in response to graded exercise.
AB  - Heart rate (HR) is a valuable and widespread measure for physical training
      programs, although its description of conditioning is limited to the cardiac
      response to exercise. More comprehensive measures of exercise adaptation include
      cardiac output (Q), stroke volume (SV) and oxygen uptake (VO2), but these
      physiological parameters can be measured only with cumbersome equipment installed
      in clinical settings. In this work, we explore the ability of pulse transit time
      (PTT) to represent a valuable pairing with HR for indirectly estimating Q, SV and
      VO2 non-invasively. PTT was measured as the time interval between the peak of the
      electrocardiographic (ECG) R-wave and the onset of the photoplethysmography (PPG)
      waveform at the periphery (i.e. fingertip) with a portable sensor. Fifteen
      healthy young subjects underwent a graded incremental cycling protocol after
      which HR and PTT were correlated with Q, SV and VO2 using linear mixed models.
      The addition of PTT significantly improved the modeling of Q, SV and VO2 at the
      individual level ([Formula: see text] for SV, 0.548 for Q, and 0.771 for VO2)
      compared to predictive models based solely on HR ([Formula: see text] for SV,
      0.503 for Q, and 0.745 for VO2). While challenges in sensitivity and artifact
      rejection exist, combining PTT with HR holds potential for development of novel
      wearable sensors that provide exercise assessment largely superior to HR
      monitors. 

PMID- 25856083
TI  - Preterm prelabor rupture of membranes and outcome of very-low-birth-weight
      infants in the German Neonatal Network.
AB  - OBJECTIVE: It was the aim of our study to evaluate the independent effect of
      preterm prelabor rupture of membranes (PPROM) as a cause of preterm delivery on
      mortality during primary hospital stay and significant morbidities in very-low
      birth-weight (VLBW) infants < 32 weeks of gestation. DESIGN: Observational,
      epidemiological study design. SETTING: Population-based cohort, German Neonatal
      Network (GNN). POPULATION: 6102 VLBW infants were enrolled in GNN from 2009-2012,
      n=4120 fulfilled criteria for primary analysis (< 32 gestational weeks, no pre
      eclampsia, HELLP (highly elevated liver enzymes and low platelets syndrome) or
      placental abruption as cause of preterm birth). METHODS: Multivariable logistic
      regression analyses included PPROM as potential risk factors for adverse outcomes
      and well established items such as gestational age in weeks, birth weight,
      antenatal steroids, center, inborn delivery, multiple birth, gender and being
      small-for-gestational-age. RESULTS: PPROM as cause of preterm delivery had no
      independent effect on the risk of early-onset sepsis, clinical sepsis and blood
      culture proven sepsis, while gestational age proved to be the most important
      contributor to sepsis risk. The diagnosis of PPROM was associated with an
      increased risk for bronchopulmonary dysplasia (BPD; OR: 1.25, 95% CI: 1.02-1.55,
      p=0.03) but not with other major outcomes. CONCLUSIONS: The diagnosis of PPROM
      per se is not associated with adverse outcome in VLBW infants < 32 weeks apart
      from a moderately increased risk for BPD. Randomized controlled trials with
      primary neonatal outcomes are needed to determine which subgroup of VLBW infants
      benefit from expectant or intentional management of PPROM.

PMID- 25856086
TI  - Chikungunya Virus Infection and Bilateral Stromal Keratouveitis.

PMID- 25856087
TI  - Skin image illumination modeling and chromophore identification for melanoma
      diagnosis.
AB  - The presence of illumination variation in dermatological images has a negative
      impact on the automatic detection and analysis of cutaneous lesions. This paper
      proposes a new illumination modeling and chromophore identification method to
      correct lighting variation in skin lesion images, as well as to extract melanin
      and hemoglobin concentrations of human skin, based on an adaptive bilateral
      decomposition and a weighted polynomial curve fitting, with the knowledge of a
      multi-layered skin model. Different from state-of-the-art approaches based on the
      Lambert law, the proposed method, considering both specular reflection and
      diffuse reflection of the skin, enables us to address highlight and strong
      shading effects usually existing in skin color images captured in an uncontrolled
      environment. The derived melanin and hemoglobin indices, directly relating to the
      pathological tissue conditions, tend to be less influenced by external imaging
      factors and are more efficient in describing pigmentation distributions.
      Experiments show that the proposed method gave better visual results and superior
      lesion segmentation, when compared to two other illumination correction
      algorithms, both designed specifically for dermatological images. For computer
      aided diagnosis of melanoma, sensitivity achieves 85.52% when using our
      chromophore descriptors, which is 8~20% higher than those derived from other
      color descriptors. This demonstrates the benefit of the proposed method for
      automatic skin disease analysis. 

PMID- 25856088
TI  - Circulating monoclonal light chains and acute kidney injury: the role of the
      renal biopsy with emphasis on ultrastructural evaluation in assessing and
      understanding renal injury.
AB  - Tubular interstitial injury as a consequence of circulating monotypical light
      chains in patients with an underlying plasma cell dyscrasia may be difficult to
      identify. Renal involvement is a common early manifestation in these patients,
      and accurate/careful pathologic evaluation can uncover an underlying plasma cell
      dyscrasia. While immunofluorescence evaluation can detect monotypical deposition
      of light chains in the tubular interstitial compartment and may suggest a
      possible underlying plasma cell dyscrasia, electron microscopic examination is
      crucial in documenting such involvement. Ultrastructural immunolabeling can help
      in solidifying the pathological assessment. 

PMID- 25856089
TI  - The role of partnerships in U.S. Food Policy Council policy activities.
AB  - Food Policy Councils (FPC) help to identify and address the priorities of local,
      state, and regional food systems with the goal of improving food systems through
      policy. There is limited research describing FPCs' strategies for accomplishing
      this goal. As part of a larger study examining FPC policy efforts, this paper
      investigates the role of partnerships in food systems policy change. We conducted
      interviews with representatives from 12 purposefully selected FPCs in the United
      States and 6 policy experts identified by the selected FPC representatives to
      document and describe their policy work. One theme that emerged from those
      interviews was the role of partners. Interviewees described a range of partners
      (e.g., stakeholders from government, business, and education) and credited FPC
      partnerships with advancing their policy goals by increasing the visibility and
      credibility of FPCs, focusing their policy agenda, connecting FPCs to key policy
      inputs (e.g., local food community knowledge and priorities), and obtaining
      stakeholder buy-in for policy initiatives. Partnerships were also described as
      barriers to policy progress when partners were less engaged or had either
      disproportionate or little influence in a given food sector. Despite these
      challenges, partnerships were found to be valuable for FPCs efforts to
      effectively engage in the food policy arena. 

PMID- 25856090
TI  - Could inducible protein-10 and heparin-binding hemagglutinin improve the
      detection of Mycobacterium tuberculosis-infected subjects in a country with low
      incidence of tuberculosis?
AB  - BACKGROUND: This study aimed to evaluate inducible protein-10 (IP-10) as a
      biomarker besides interferon-gamma (IFN-gamma) to improve the identification of
      active tuberculosis (TB) and latent tubercular infection (LTBI) in a country with
      a low incidence of TB. METHODS: Whole blood from Mycobacterium tuberculosis
      infected subjects was stimulated with region-of-difference-1 (RD1)-specific
      peptides and with heparin-binding hemagglutinin (HBHA) to determine the release
      of IP-10 and IFN-gamma. RESULTS: No statistically significant difference was
      observed between positive rates of IP-10 and IFN-gamma after RD1-specific peptide
      stimulation in the TB and LTBI groups; a different response was detected in
      QuantiFERON TB-gold test-negative (QFT-) subjects. A significantly different
      proportion of positive responses was observed between IP-10 and IFN-gamma
      following HBHA stimulation in the TB group and in the QFT- group but not in the
      LTBI group. CONCLUSIONS: The IP-10 test seemed to identify false-negative QFT
      results in some subjects with a positive IFN-gamma/IP-10/HBHA pattern.

PMID- 25856091
TI  - The relationship between the pre-admission CHA2DS2-VASc score and proximal artery
      occlusion in patients with acute stroke and atrial fibrillation.
AB  - BACKGROUND AND PURPOSE: The CHA2DS2-VASc score is associated with severity and
      outcome of ischaemic stroke in patients with atrial fibrillation (AF). It was
      hypothesized that a high CHA2DS2-VASc score was related to severity and outcome
      because of its association with proximal artery occlusion (PAO). This study aimed
      to elucidate the relationship between the CHA2DS2-VASc score and PAO and to
      determine whether the effect of the CHA2DS2-VASc score on severity or outcome is
      independent of PAO. METHODS: Acute stroke patients with AF were retrospectively
      enrolled. PAO was defined as occlusion at the internal carotid artery or proximal
      middle cerebral artery on admission magnetic resonance angiography. Multivariable
      analyses were performed to identify independent factors associated with PAO and
      determine the associations of the CHA2DS2-VASc score with the initial National
      Institutes of Health Stroke Scale (NIHSS) score and poor functional outcome
      (discharge modified Rankin scale score 4-6). RESULTS: In all, 213 patients [102
      women; median age 80 (interquartile range 71-86) years; NIHSS score 16 (9-22)]
      were enrolled. On multivariable analysis, the CHA2DS2-VASc score (odds ratio
      1.40, 95% confidence interval 1.12-1.76 per 1 point) was independently associated
      with PAO and correlated with the initial NIHSS score (standardized coefficient
      0.198, P = 0.017). This association was not significant after further adjustment
      for PAO (0.080, P = 0.241). The CHA2DS2-VASc score was independently related to
      poor outcome even adjusted for PAO (odds ratio 1.39, 95% confidence interval 1.03
      1.88). CONCLUSION: The CHA2DS2-VASc score was associated with PAO in acute
      ischaemic stroke patients with AF. The CHA2DS2-VASc score may be correlated with
      the NIHSS score through the presence of PAO and with poor functional outcome
      independently of PAO.

PMID- 25856092
TI  - Correction: Dimethyloxalylglycine prevents bone loss in ovariectomized C57BL/6J
      mice through enhanced angiogenesis and osteogenesis.

PMID- 25856093
TI  - Real-time sequence-validated loop-mediated isothermal amplification assays for
      detection of Middle East respiratory syndrome coronavirus (MERS-CoV).
AB  - The Middle East respiratory syndrome coronavirus (MERS-CoV), an emerging human
      coronavirus, causes severe acute respiratory illness with a 35% mortality rate.
      In light of the recent surge in reported infections we have developed asymmetric
      five-primer reverse transcription loop-mediated isothermal amplification (RT
      LAMP) assays for detection of MERS-CoV. Isothermal amplification assays will
      facilitate the development of portable point-of-care diagnostics that are crucial
      for management of emerging infections. The RT-LAMP assays are designed to amplify
      MERS-CoV genomic loci located within the open reading frame (ORF)1a and ORF1b
      genes and upstream of the E gene. Additionally we applied one-step strand
      displacement probes (OSD) for real-time sequence-specific verification of LAMP
      amplicons. Asymmetric amplification effected by incorporating a single loop
      primer in each assay accelerated the time-to-result of the OSD-RT-LAMP assays.
      The resulting assays could detect 0.02 to 0.2 plaque forming units (PFU) (5 to 50
      PFU/ml) of MERS-CoV in infected cell culture supernatants within 30 to 50 min and
      did not cross-react with common human respiratory pathogens. 

PMID- 25856094
TI  - A computer-simulation study on the effects of MRI voxel dimensions on carotid
      plaque lipid-core and fibrous cap segmentation and stress modeling.
AB  - BACKGROUND: The benefits of a decreased slice thickness and/or in-plane voxel
      size in carotid MRI for atherosclerotic plaque component quantification accuracy
      and biomechanical peak cap stress analysis have not yet been investigated in
      detail because of practical limitations. METHODS: In order to provide a
      methodology that allows such an investigation in detail, numerical simulations of
      a T1-weighted, contrast-enhanced, 2D MRI sequence were employed. Both the slice
      thickness (2 mm, 1 mm, and 0.5 mm) and the in plane acquired voxel size
      (0.62x0.62 mm2 and 0.31x0.31 mm2) were varied. This virtual MRI approach was
      applied to 8 histology-based 3D patient carotid atherosclerotic plaque models.
      RESULTS: A decreased slice thickness did not result in major improvements in
      lumen, vessel wall, and lipid-rich necrotic core size measurements. At 0.62x0.62
      mm2 in-plane, only a 0.5 mm slice thickness resulted in improved minimum fibrous
      cap thickness measurements (a 2-3 fold reduction in measurement error) and only
      marginally improved peak cap stress computations. Acquiring voxels of 0.31x0.31
      mm2 in-plane, however, led to either similar or significantly larger improvements
      in plaque component quantification and computed peak cap stress. CONCLUSIONS:
      This study provides evidence that for currently-used 2D carotid MRI protocols, a
      decreased slice thickness might not be more beneficial for plaque measurement
      accuracy than a decreased in-plane voxel size. The MRI simulations performed
      indicate that not a reduced slice thickness (i.e. more isotropic imaging), but
      the acquisition of anisotropic voxels with a relatively smaller in-plane voxel
      size could improve carotid plaque quantification and computed peak cap stress
      accuracy.

PMID- 25856100
TI  - Correction: Clinical significance of cerebral microbleeds locations in CADASIL
      with R544C NOTCH3 mutation.

PMID- 25856095
TI  - From shelf to shelf: assessing historical and contemporary genetic
      differentiation and connectivity across the Gulf of Mexico in Gag, Mycteroperca
      microlepis.
AB  - Describing patterns of connectivity among populations of species with widespread
      distributions is particularly important in understanding the ecology and
      evolution of marine species. In this study, we examined patterns of population
      differentiation, migration, and historical population dynamics using
      microsatellite and mitochondrial loci to test whether populations of the
      epinephelid fish, Gag, Mycteroperca microlepis, an important fishery species, are
      genetically connected across the Gulf of Mexico and if so, whether that
      connectivity is attributable to either contemporary or historical processes.
      Populations of Gag on the Campeche Bank and the West Florida Shelf show
      significant, but low magnitude, differentiation. Time since divergence/expansion
      estimates associated with historical population dynamics indicate that any
      population or spatial expansions indicated by population genetics would have
      likely occurred in the late Pleistocene. Using coalescent-based approaches, we
      find that the best model for explaining observed spatial patterns of contemporary
      genetic variation is one of asymmetric gene flow, with movement from Campeche
      Bank to the West Florida Shelf. Both estimated migration rates and ecological
      data support the hypothesis that Gag populations throughout the Gulf of Mexico
      are connected via present day larval dispersal. Demonstrating this greatly
      expanded scale of connectivity for Gag highlights the influence of "ghost"
      populations (sensu Beerli) on genetic patterns and presents a critical
      consideration for both fisheries management and conservation of this and other
      species with similar genetic patterns. 

PMID- 25856101
TI  - Lactic Acid Bacteria and Bifidobacteria-Inhibited Staphylococcus epidermidis.
AB  - INTRODUCTION: Lactic acid bacteria (LAB) and bifidobacteria are able to produce
      antimicrobial compounds to inhibit opportunisticwounding skin pathogen. The
      antimicrobial compounds produced are organic acids, putative bacteriocin,
      hydrogen peroxide, and diacetyl. Staphylococcus epidermidis is well-known as an
      opportunistic wounding skin pathogen in wound infections related to implanted
      medical devices. OBJECTIVE: To screen 87 strains of LAB and 3 strains of
      bifidobacteria for antimicrobial activity against Staphylococcus
      epidermidis.Additionally, this study sought to determine and quantify types of
      antimicrobial compounds produced by LAB. MATERIALS AND METHODS: Inhibitory
      activity of LAB and bifidobacteria on S. epidermidis was assessed with the
      spectrophotometric method using a 96-well microplate reader. Characterization of
      cell-free supernatant (CFS) was done using analytical methods. Lactobacillus
      fermentum (collected by the Bioprocess Department at the Universiti Sains
      Malaysia [BD]) 1912d, Lactobacillus casei BD 1415b, Lactobacillus fermentum BD
      8313a, Pediococcus pentosaceus BD 1913b, and Weissella cibaria (collected by the
      Food Technology Department at the Universiti Sains Malaysia [FTDC]) 8643 with
      high percentage of inhibition (P < 0.05), ranging from 73.7% to 88.2%, as
      compared to the control, were selected for subsequent analyses. Upon
      neutralization, the antimicrobial activity showed a drastic drop (P < 0.05) in
      the percentage of inhibition. Concentrations of the inhibitive metabolites were
      produced in varying amounts and were strain dependent. RESULTS: Results
      demonstrated that lactic acid in all strains was produced in a more predominant
      amount than acetic acid. Protein concentration production ranged from 0.081-0.215
      mg/mL. L. fermentum BD 1912d yielded as much as 0.014 mg/mL hydrogen peroxide,
      which was significantly higher than other strains studied. Diacetyl was produced
      in a higher concentration by Weissella cibaria FTDC 8643 at 2.884 ng/mL; the
      lowest concentration of 0.465 ng/mL was produced by Ped. pentosaceus BD 1913b.
      CONCLUSION: Antimicrobial metabolites from CFS of lactic acid bacteria were
      effective in repressing the growth of opportunistic wounding dermal pathogen
      Staphylococcus epidermidis.

PMID- 25856102
TI  - Utility of proximally based sural fasciocutaneous flap for knee and proximal
      lower leg defects.

PMID- 25856103
TI  - Actinomycetoma leg ulcers in north India.
AB  - INTRODUCTION: Actinomycetoma is a chronic subcutaneous infection caused by
      aerobic branching actinomycetes. Its clinical features are firm tumefaction of
      the affected site and the presence of abscesses, nodules, and sinuses that drain
      a seropurulent exudate containing filamenting granules. Cutaneous actinomycetoma
      has traditionally been deemed uncommon in the northern part of India, but recent
      studies have refuted this long-held notion. Thus, clinicians have to be more
      vigilant when they come across patients with long-standing cutaneous lesions with
      typical mycetomic features, as early diagnosis and treatment hold the key to a
      cure. MATERIALS AND METHODS: This prospective study was carried out from June
      2009 to December 2012 and comprises 13 cases of chronic nonhealing ulcers of the
      lower limb subsequently diagnosed as mycetoma. Socioetiological aspects,
      prevalence, early diagnosis, and treatment modalities of this condition are
      described in the study along with a simple, yet inclusive, scoring system to
      evaluate the post-treatment results. RESULTS: Ten out of 13 cases with clinical
      suspicion of actinomycetoma were diagnosed with the condition. A majority of
      these diagnosed patients were middle aged and belonged to lower socioeconomic
      status. There was no sexual preponderance. Early treatment in the form of
      modified Welsh regime (amikacin + cotrimoxazole + rifampicin) was started and
      showed acceptable results. Post-treatment outcomes were measured on the basis of
      a new scoring system (Masoodi's score) devised by the authors. Two patients had a
      score of > 7 (good), 5 patients had a score of 4-6 (fair), and 3 patients had a
      score of <= 3 (poor). CONCLUSION: Correct identification of the infective
      aetiological agent is imperative to direct therapy against actinomycetoma.
      Treatment success depends on an early diagnosis and instigation of treatment.
      Efficacy of chemotherapy, if started after an early diagnosis in the form of
      modified Welsh regime, produces acceptable results in the form of clinical and
      physical remission or cure. The functional and cosmetic parameters do not respond
      as well to treatment and the authors propose a new scoring system which takes
      into account the post-treatment results in totality.

PMID- 25856105
TI  - Correction: Extremely low genetic diversity indicating the endangered status of
      Ranodon sibiricus (Amphibia: Caudata) and implications for phylogeography.

PMID- 25856104
TI  - Codon optimisation is key for pernisine expression in Escherichia coli.
AB  - BACKGROUND: Pernisine is an extracellular serine protease from the
      hyperthermophilic Archaeon Aeropyrum pernix K1. Low yields from the natural host
      and expression problems in heterologous hosts have limited the potential
      applications of pernisine in industry. METHODOLOGY/ PRINCIPAL FINDINGS: The
      challenges of pernisine overexpression in Escherichia coli were overcome by codon
      preference optimisation and de-novo DNA synthesis. The following forms of the
      pernisine gene were cloned into the pMCSGx series of vectors and expressed in E.
      coli cells: wild-type (pernisinewt), codon-optimised (pernisineco), and codon
      optimised with a S355A mutation of a predicted active site (pernisineS355Aco).
      The fusion-tagged pernisines were purified using fast protein liquid
      chromatography equipped with Ni2+ chelate and gel filtration chromatography
      columns. The identities of the resultant proteins were confirmed with N-terminal
      sequencing, tandem mass spectrometry analysis, and immunodetection. Pernisinewt
      was not expressed in E. coli at detectable levels, while pernisineco and
      pernisineS355Aco were expressed and purified as 55-kDa proforms with yields of
      around 10 mg per litre E. coli culture. After heat activation of purified
      pernisine, the proteolytic activity of the mature pernisineco was confirmed using
      zymography, at a molecular weight of 36 kDa, while the mutant pernisineS355Aco
      remained inactive. Enzymatic performances of pernisine evaluated under different
      temperatures and pHs demonstrate that the optimal enzymatic activity of the
      recombinant pernisine is ca. 100 degrees C and pH 7.0, respectively. CONCLUSIONS/
      SIGNIFICANCE: These data demonstrate that codon optimisation is crucial for
      pernisine overexpression in E. coli, and that the proposed catalytic Ser355 has
      an important role in pernisine activity, but not in its activation process.
      Pernisine is activated by autoproteolytical cleavage of its N-terminal proregion.
      We have also confirmed that the recombinant pernisine retains the characteristics
      of native pernisine, as a calcium modulated thermostable serine protease.

PMID- 25856107
TI  - Prognostic Significance of Peritumoral Edema in Patients With Vestibular
      Schwannomas.
AB  - BACKGROUND: Peritumoral edema (PTE) in skull base meningiomas correlates to the
      absence of an arachnoid plane and difference in outcome. In vestibular
      schwannomas (VS), PTE and its significance for microsurgery and outcome have
      never been systematically evaluated. OBJECTIVE: To evaluate whether PTE
      correlates with tumor characteristics, the presence of an arachnoid plane, and
      outcome. METHODS: A retrospective study of the institutional database. PTE was
      evaluated on fluid-attenuated inversion recovery magnetic resonance images.
      Preoperative patient data and intraoperative tumor features (presence of tumor
      pseudocapsule, vascularity, degree of adhesion/invasion of the arachnoid) were
      noted. Outcome measures were completeness of removal, neurological outcome, and
      complication rate. These parameters in patients with PTE (group A) were
      correlated to those in matched series without edema (group B). RESULTS: Thirty
      patients presented with PTE (5%). The mean VS size was 3.4 cm. No major
      differences in the degree of adhesion or presence of an arachnoid plane were
      found. VS with PTE were more frequently hypervascular (26.7% in group A vs 6.7%
      in group B). The presence of PTE in VS was not related to surgical radicality. VS
      with PTE had worse early postoperative facial nerve function, but at 12 months,
      there was no major difference. VS with PTE were prone to cause postoperative
      hemorrhages in the tumor bed. CONCLUSION: PTE in VS does not correlate with the
      degree of tumor adhesion and the presence of an arachnoid dissection plane. The
      radicality of tumor removal and long-term functional outcome in patients with and
      without PTE was similar. VS with PTE are more vascular and prone to cause
      postoperative hemorrhages. Therefore, meticulous hemostasis is advisable.

PMID- 25856106
TI  - Oakleaf: an S locus-linked mutation of Primula vulgaris that affects leaf and
      flower development.
AB  - In Primula vulgaris outcrossing is promoted through reciprocal herkogamy with
      insect-mediated cross-pollination between pin and thrum form flowers. Development
      of heteromorphic flowers is coordinated by genes at the S locus. To underpin
      construction of a genetic map facilitating isolation of these S locus genes, we
      have characterised Oakleaf, a novel S locus-linked mutant phenotype. We combine
      phenotypic observation of flower and leaf development, with classical genetic
      analysis and next-generation sequencing to address the molecular basis of
      Oakleaf. Oakleaf is a dominant mutation that affects both leaf and flower
      development; plants produce distinctive lobed leaves, with occasional ectopic
      meristems on the veins. This phenotype is reminiscent of overexpression of Class
      I KNOX-homeodomain transcription factors. We describe the structure and
      expression of all eight P. vulgaris PvKNOX genes in both wild-type and Oakleaf
      plants, and present comparative transcriptome analysis of leaves and flowers from
      Oakleaf and wild-type plants. Oakleaf provides a new phenotypic marker for
      genetic analysis of the Primula S locus. We show that none of the Class I PvKNOX
      genes are strongly upregulated in Oakleaf leaves and flowers, and identify
      cohorts of 507 upregulated and 314 downregulated genes in the Oakleaf mutant. 

PMID- 25856108
TI  - Bifid Anterior and Posterior Arches of Atlas: Surgical Implication and Analysis
      of 70 Cases.
AB  - BACKGROUND: On reviewing the database of patients with craniovertebral junction
      anomalies, the authors identified 70 patients with a bifid posterior arch of
      atlas. OBJECTIVE: To speculate on the pathogenesis of spondyloschisis of both the
      anterior and posterior arches of atlas, particularly as it relates to
      atlantoaxial instability. METHODS: Seventy patients with bifid anterior and
      posterior arches were identified by a retrospective review of the database from
      2007 to 2013. RESULTS: The ages of the patients ranged from 14 months to 50
      years. The patients were divided into 3 groups. Group 1 (3 patients) had multiple
      additional spinal bony and neural abnormalities. Group 2 (34 patients) had mobile
      and partially (5) or completely (29) reducible atlantoaxial dislocation. Group 3
      (33 patients) had atlantoaxial instability and related basilar invagination. The
      os odontoideum was identified in 21 patients, and C2-3 fusion was seen in 24
      patients. Two of 3 patients in group 1 were treated conservatively and without
      any surgery. All patients in groups 2 and 3 were surgically treated. Surgery was
      done using lateral mass plate/rod and screw fixation techniques. The general
      observation during surgery included identification of discrete movements of both
      halves of the atlas, lateral positioning of the facets of atlas in relation to
      the facets of the axis and occipital condyle and closer approximation of the
      occipital bone, atlas, and axis resulting in "crumpling" of bone and neural
      elements. CONCLUSION: Understanding of the pathogenesis and mechanical
      alterations in cases with a bifid arch of atlas can assist in evaluating the
      clinical implications and in conduct of surgery.

PMID- 25856109
TI  - Single-Isocenter Frameless Volumetric Modulated Arc Radiosurgery for Multiple
      Intracranial Metastases.
AB  - BACKGROUND: Stereotactic radiosurgery (SRS) is a well-accepted treatment for
      patients with intracranial metastases, but outcomes with volumetric modulated arc
      radiosurgery (VMAR) are poorly described. OBJECTIVE: To report our initial
      clinical experience applying a novel single-isocenter technique to frameless VMAR
      for simultaneous treatment of multiple intracranial metastases. METHODS: We
      performed a retrospective analysis of 15 patients undergoing frameless VMAR for
      multiple intracranial metastases using a single, centrally located isocenter in
      the period 2009 and 2011. Of these, 3 patients were treated for progressive or
      recurrent intracranial disease. A total of 62 metastases (median, 3 per patient;
      range, 2-13) were treated to a median dose of 20 Gy (range, 15-30 Gy). Three
      patients were treated with fractionated SRS. Follow-up including clinical
      examination and magnetic resonance imaging (MRI) occurred every 3 months.
      RESULTS: The median follow-up for all patients was 7.1 months (range, 1.1-24.3),
      with 11 patients (73.3%) followed until death. For the remaining 4 patients alive
      at the time of analysis, the median follow-up was 19.6 months (range, 9.2-24.3).
      Local control at 6 and 12 months was 91.7% (95% confidence interval [CI], 84.6%
      100.0%) and 81.5% (95% CI, 67.9%-100.0%), respectively. Regional failure was
      observed in 9 patients (60.0%), and 7 patients (46.7%) received salvage therapy.
      Overall survival at 6 months was 60.0% (95% CI, 40.3%-88.2%). Grade 3 or higher
      treatment-related toxicity was not observed. The median total treatment time was
      7.2 minutes (range, 2.8-13.2 minutes). CONCLUSION: Single-isocenter, frameless
      VMAR for multiple intracranial metastases is a promising technique that may
      provide similar clinical outcomes compared with conventional radiosurgery.

PMID- 25856110
TI  - Strategies for Computed Tomography Radiation Dose Reduction in Pediatric
      Neuroimaging.
AB  - BACKGROUND: Radiation exposure from diagnostic imaging is a significant concern,
      particularly in the care of pediatric patients. Computed tomography (CT) scanning
      is a significant source of radiation. OBJECTIVE: To demonstrate that diagnostic
      quality CT images can be obtained while minimizing the effective radiation dose
      to the patient. METHODS: In this retrospective cross-sectional study, noncontrast
      head CT scan data were reviewed, and indications for scans and estimated
      radiation dose delivered were recorded. The estimated effective radiation dose
      (EERD) for each CT protocol was reviewed. RESULTS: We identified 251 head CT
      scans in a single month. Of these, 96 scans were using a low-dose shunt protocol
      with a mean EERD of 0.82 mSv. The remaining 155 scans were performed using the
      standard protocol, and the mean EERD was 1.65 mSv. Overall, the EERD was
      minimized while maintaining diagnostic scan quality. CONCLUSION: Although
      replacing a CT with magnetic resonance imaging is ideal to completely avoid
      ionizing radiation, this is not always practical or preferred. Therefore, it is
      important to have CT protocols in place that minimize radiation dose without
      sacrificing diagnostic quality. The protocols in place at our institution could
      be replicated at other academic and community hospitals and imaging centers.

PMID- 25856111
TI  - Diagnostic Value and Safety of Brain Biopsy in Patients With Cryptogenic
      Neurological Disease: A Systematic Review and Meta-analysis of 831 Cases.
AB  - BACKGROUND: The role of brain biopsy in patients with cryptogenic neurological
      disease is uncertain. OBJECTIVE: To determine the risks and benefits of
      diagnostic brain biopsy for nonneoplastic indications in immunocompetent
      patients. METHODS: Appropriate studies were identified by searching electronic
      databases. RESULTS: We screened 3645 abstracts and included 20 studies with a
      total of 831 patients. Indications for biopsy were: (1a) severe neurological
      disease of unknown etiology in adults (n = 7) and (1b) in children (n = 2); (2)
      suspected primary angiitis of the central nervous system (PACNS) (n = 3); (3)
      chronic meningitis of unknown cause (n = 3); (4) atypical dementia (n = 4); and
      (5) nonneoplastic disease (n = 1). Diagnostic success rates calculated for
      subgroups were 51.3% (34.5-68.1) for 1a, 53.8% (42.9-64.5) for 1b, 74.7% (64.0
      84.1) for 2, 30.3% (17.2-45.4) for 3, and 60.8% (41.2-78.8) for 4. Clinical
      impact rates were 30.5% (13.6-50.6) for 1a (n = 6), 67.1% (42.8-87.3) for 1b (n =
      2), 8.3% (2.3-20.0) for 3 (n = 1), and 14.2% (6.5-24.3) for 4 (n = 2). Lymphoma
      (n = 32) and Creutzfeldt-Jakob disease (n = 30) were the most common diagnoses on
      the final histopathology reports of positive brain biopsies in 1a. In 1b,
      encephalitis (n = 7), PACNS (n = 6), and demyelination (n = 6) were the most
      common. The odds ratio for achieving a diagnostic biopsy when there was a
      radiological target was 3.70 (P = .014, 95% confidence interval, 1.31-10.42).
      CONCLUSION: Brain biopsy in cryptogenic neurological disease was associated with
      the highest diagnostic yield in patients with suspected PACNS. The greatest
      clinical impact was seen in children with cryptogenic neurological disease. The
      presence of a radiological target was associated with a higher diagnostic yield.

PMID- 25856112
TI  - Comparison of Stent-Assisted Coiling vs Coiling Alone in 563 Intracranial
      Aneurysms: Safety and Efficacy at a High-Volume Center.
AB  - BACKGROUND: Stent-assisted coiling has been used in both unruptured and ruptured
      aneurysms, but the safety and efficacy still remain controversial. OBJECTIVE: To
      compare the safety and efficacy of stent-assisted coiling with coiling alone for
      intracranial aneurysms. METHODS: We retrospectively reviewed 512 patients treated
      by endovascular coiling or stent-assisted coiling over a 1-year period. The
      patients' clinical and imaging information was recorded. Procedure-related
      complication rates, recurrence rates, and clinical outcomes were analyzed in both
      the total aneurysms and the subgroups of ruptured and unruptured aneurysms.
      RESULTS: A total of 243 patients were treated by coiling alone and 269 patients
      were treated by stent-assisted coiling. Procedure-related complications occurred
      in 6.2% of patients in the coiling-alone group compared with 6.3% in the stent
      assisted coiling group. The procedural permanent morbidity and mortality rates
      were 1.6% (4/243) and 1.2% (3/243), respectively, in the coiling-alone group and
      1.1% (3/269) and 1.5% (4/269), respectively, in the stent-assisted coiling group.
      A significantly lower recurrence rate was found in the stent-assisted coiling
      group compared with the coiling-alone group (5.2% vs 16.5%, P = .002). In a
      comparison of subgroups of ruptured and unruptured aneurysms, the procedural
      complications rates were comparable in the 2 groups, with a lower recurrence rate
      in the stent-assisted coiling group. Multivariate analysis showed that larger
      aneurysm size and higher Hunt and Hess grade were predictors of procedural
      morbidity; larger aneurysm size, ruptured aneurysm, anterior circulation
      aneurysms, initial incomplete occlusion, and lack of stent assistance were
      predictors of recurrence. CONCLUSION: Compared with coiling alone, stent-assisted
      coiling may achieve lower recurrence rates, with comparable procedure-related
      complications and clinical outcomes in both ruptured and unruptured aneurysms.

PMID- 25856113
TI  - The Effect of Timing of Concurrent Chemoradiation in Patients With Newly
      Diagnosed Glioblastoma.
AB  - BACKGROUND: The effect of timing of initiation of concurrent radiation and
      chemotherapy after surgery on outcome of patients with glioblastoma (GBM) remains
      unclear. OBJECTIVE: To further explore this issue, we analyzed 4 clinical trials
      for patients newly diagnosed with GBM receiving concurrent and adjuvant
      temozolomide. METHODS: The cohort study included 198 adult patients with newly
      diagnosed supratentorial GBM who were enrolled from 2004 to 2010 in 4 clinical
      trials consisting of radiation plus temozolomide and an experimental agent. The
      interval to initiation of therapy was determined from the time of surgical
      resection. The partitioning deletion/substitution/addition algorithm was used to
      determine the cutoff points for timing of chemoradiation at which there was a
      significant difference in overall survival (OS) and progression-free survival
      (PFS). RESULTS: The median wait time between surgery and initiation of concurrent
      chemoradiation was 29.5 days (range, 7-56 days). A short delay in chemoradiation
      administration (at 30-34 days) was predictive of prolonged OS (hazard ratio [HR]:
      0.63, P = .03) and prolonged PFS (HR: 0.68, P = .06) compared with early
      initiation of concurrent chemoradiation (<30 days), after adjusting for protocol
      and baseline prognostic variables including extent of resection by multivariate
      analysis. A longer delay to chemoradiation beyond 34 days was not associated with
      improved OS or PFS compared with early initiation (HR: 0.94, P = .77 and HR:
      0.91, P = .63, respectively). CONCLUSION: A short delay in the start of
      concurrent chemoradiation is beyond the classic paradigm of 4 weeks post
      resection and may be associated with prolonged OS and PFS.

PMID- 25856114
TI  - An Endoscopic Roadmap of the Internal Carotid Artery.

PMID- 25856115
TI  - In Reply: An Endoscopic Roadmap of the Internal Carotid Artery.

PMID- 25856116
TI  - Caffeine-induced psychiatric manifestations: a review.
AB  - The association between caffeine consumption and various psychiatric
      manifestations has long been observed. We present two cases that show the ability
      of caffeine to induce psychotic and manic symptoms, and we also review the extant
      literature on caffeine-induced psychiatric manifestations. On the basis of our
      own and others' findings, we suggest that caffeine may be related to not only de
      novo psychotic or mood symptoms but also to aggravation of pre-existing psychotic
      or mood disorders. We therefore suggest that caffeine consumption among patients
      with mood or psychotic symptoms should be assessed carefully in clinical practice
      as part of routine psychiatric evaluations. 

PMID- 25856118
TI  - Enhanced photocatalytic activity in electrospun bismuth vanadate nanofibers with
      phase junction.
AB  - BiVO4 nanofibers were successfully prepared by electrospinning and precisely
      controlled heat treatment. The obtained BiVO4 nanofibers showed an enhanced
      photocatalytic activity in the degradation of rhodamine-B under visible light
      irradiation. The as-prepared nanofibers were characterized by means of numerous
      techniques. The enhanced photocatalyst activity is attributed to the formation of
      a phase junction of tetragonal sheelite (s-t) and monoclinic sheelite (s-m)
      phases in the electrospun BiVO4 nanofibers. We have also investigated the band
      structure of BiVO4 using first principle calculation. The main photon transition
      mechanism of the photocatalyst should be from the O 2p to V 3d state of s-m/t
      BiVO4 nanofibers. 

PMID- 25856119
TI  - Simulation of the resonance Raman spectra for 5-halogenated (F, Cl, and Br)
      uracils.
AB  - The resonance Raman spectra of the 5-halogenated (F, Cl, and Br) uracils are
      simulated via the Herzberg-Teller (HT) short-time dynamics formalism. The
      gradient of the S1 excited state is computed at the CAMB3LYP/aug-cc-pVTZ level of
      theory in the conductor-like polarizable continuum model for water (C-PCM, H2O),
      based on the equilibrium geometry determined using PBE0/aug-cc-pVTZ in H2O (C
      PCM). The simulated resonance Raman spectra show good agreement with the
      experimental spectra in terms of both peak positions and intensities. The
      differences between the resonance Raman spectra of the three 5-halogenated
      uracils, caused by the effect of halogen substitution, are examined in terms of
      ground-state normal-mode eigenvectors and excited-state Cartesian gradients,
      according to the HT formalism. The differences in the normal-mode eigenvectors
      and excited-state Cartesian gradients between 5-fluorouracil and 5-chlorouracil
      are used to interpret the dissimilarity between their resonance Raman spectra.
      Meanwhile, the similarity between the spectra of 5-chlorouracil and 5-bromouracil
      is explained by the correspondence between their normal modes and excited-state
      gradients. 

PMID- 25856120
TI  - Antibiotic-resistant bacteria: prevalence in food and inactivation by food
      compatible compounds and plant extracts.
AB  - Foodborne antibiotic-resistant pathogenic bacteria such as Campylobacter jejuni,
      Bacillus cereus, Clostridium perfringens, Escherichia coli, Salmonella enterica,
      Staphylococcus aureus, Vibrio cholerae, and Vibrio parahemolyticus can adversely
      affect animal and human health, but a better understanding of the factors
      involved in their pathogenesis is needed. To help meet this need, this overview
      surveys and interprets much of our current knowledge of antibiotic (multidrug)
      resistant bacteria in the food chain and the implications for microbial food
      safety and animal and human health. Topics covered include the origin and
      prevalence of resistant bacteria in the food chain (dairy, meat, poultry,
      seafood, and herbal products, produce, and eggs), their inactivation by different
      classes of compounds and plant extracts and by the use of chlorine and
      physicochemical methods (heat, UV light, pulsed electric fields, and high
      pressure), the synergistic antimicrobial effects of combinations of natural
      antimicrobials with medicinal antibiotics, and mechanisms of antimicrobial
      activities and resistant effects. Possible areas for future research are
      suggested. Plant-derived and other safe natural antimicrobial compounds have the
      potential to control the prevalence of both susceptible and resistant pathogens
      in various environments. The collated information and suggested research will
      hopefully contribute to a better understanding of approaches that could be used
      to minimize the presence of resistant pathogens in animal feed and human food,
      thus reducing adverse effects, improving microbial food safety, and helping to
      prevent or treat animal and human infections. 

PMID- 25856122
TI  - Atypical Glandular Cells of Endometrial Origin and the Risk of Endometrial
      Cancer.
AB  - OBJECTIVES: To assess the risk of endometrial cancer (EC) associated with
      atypical glandular cells of endometrial origin (AGC-EM) in 2 age groups (age
      younger than 51 vs 51 years or older). METHODS: A retrospective case series was
      assembled identifying AGC from a pathology database between January 1, 2005 and
      January 1, 2009. Demographics, cervical cytology results, and final diagnoses
      (including clinically significant diseases and cancers) were recorded from the
      initial AGC diagnosis until August 30, 2011. Data were analyzed using the chi
      test to compare rates of disease between age groups. RESULTS: Among the 444
      patients with AGC, 41% (183/444) had AGC-EM. Women younger than 51 years,
      compared to those 51 years or older, had significantly lower rates of AGC-EM (35%
      [105/296] vs 53% [78/148]; p < .001; odds ratio, 0.49; 95% confidence interval,
      0.33-0.74). The rate of EC was significantly lower in those younger than 51
      years, compared to those aged 51 or older (5% [8/158] vs 19% [18/95]; p < .001;
      odds ratio, 0.23; 95% confidence interval, 0.09-0.55) in women who underwent
      endometrial biopsy. In women younger than 51 years who underwent an endometrial
      biopsy, the rate of EC had a stepwise increase across 3 subclasses of AGC (from
      AGC of endocervical origin [AGC-EC] to AGC not otherwise specified to AGC-EM) (p
      = .04). CONCLUSIONS: Women aged 51 years or older who have AGC are more likely to
      have AGC-EM and EC than women younger than 51 years. In women younger than age
      51, AGC-EM is the subclass most associated with EC while compared to 2 other
      subclasses (AGC not otherwise specified and AGC-EC).

PMID- 25856121
TI  - Sensitivity Analyses of the Change in FVC in a Phase 3 Trial of Pirfenidone for
      Idiopathic Pulmonary Fibrosis.
AB  - BACKGROUND: FVC outcomes in clinical trials on idiopathic pulmonary fibrosis
      (IPF) can be substantially influenced by the analytic methodology and the
      handling of missing data. We conducted a series of sensitivity analyses to assess
      the robustness of the statistical finding and the stability of the estimate of
      the magnitude of treatment effect on the primary end point of FVC change in a
      phase 3 trial evaluating pirfenidone in adults with IPF. METHODS: Source data
      included all 555 study participants randomized to treatment with pirfenidone or
      placebo in the Assessment of Pirfenidone to Confirm Efficacy and Safety in
      Idiopathic Pulmonary Fibrosis (ASCEND) study. Sensitivity analyses were conducted
      to assess whether alternative statistical tests and methods for handling missing
      data influenced the observed magnitude of treatment effect on the primary end
      point of change from baseline to week 52 in FVC. RESULTS: The distribution of FVC
      change at week 52 was systematically different between the two treatment groups
      and favored pirfenidone in each analysis. The method used to impute missing data
      due to death had a marked effect on the magnitude of change in FVC in both
      treatment groups; however, the magnitude of treatment benefit was generally
      consistent on a relative basis, with an approximate 50% reduction in FVC decline
      observed in the pirfenidone group in each analysis. CONCLUSIONS: Our results
      confirm the robustness of the statistical finding on the primary end point of
      change in FVC in the ASCEND trial and corroborate the estimated magnitude of the
      pirfenidone treatment effect in patients with IPF. TRIAL REGISTRY:
      ClinicalTrials.gov; No.: NCT01366209; URL: www.clinicaltrials.gov.

PMID- 25856123
TI  - Aspirin and Acetaminophen Use and the Risk of Cervical Cancer.
AB  - OBJECTIVE: In this study, we investigated whether regular use of aspirin or
      acetaminophen was associated with risk of cervical cancer in women treated at an
      American cancer hospital. METHODS: This case-control study included 328 patients
      with cervical cancer and 1,312 controls matched on age and decade enrolled.
      Controls were women suspected of having but not ultimately diagnosed with a
      neoplasm. Analgesic use was defined as regular (at least once per week for >=6
      months), frequent (>=7 tablets/week), very long term (>=11 years), or frequent,
      long term (>=7 tablets per week for >=5 years). RESULTS: Compared to nonusers,
      frequent aspirin use was associated with decreased odds of cervical cancer (odds
      ratio, 0.53; 95% confidence interval, 0.29-0.97). A slightly larger association
      was observed with frequent, long-term use of aspirin (odds ratio, 0.46; 95%
      confidence interval, 0.22-0.95). Acetaminophen use was not associated with the
      risk of cervical cancer. CONCLUSIONS: Our findings suggest that frequent and
      frequent, long-term use of aspirin is associated with decreased odds of cervical
      cancer. To our knowledge, this is the first US-based study examining these
      associations. Given the widespread use of nonsteroidal anti-inflammatory drugs
      and acetaminophen worldwide, further investigations of the possible role of
      analgesics in cervical cancer, using a larger sample size with better-defined
      dosing regimens, are warranted.

PMID- 25856124
TI  - Impact of a Video Intervention for Rural Peruvian Women With Cervical Neoplasia
      Before Loop Excisional Procedures.
AB  - OBJECTIVE: Indigenous Peruvian women have very high rates of cervical cancer.
      This study assessed the impact of an educational video on impoverished rural
      Peruvian women seeking loop excision surgery. MATERIALS AND METHODS: Women
      completed baseline, postvideo and postsurgery questionnaires that assessed
      knowledge and attitudes about the procedure. Differences between groups were
      examined using repeated measures analysis of variance. RESULTS: Women who watched
      the video were significantly more calm (2.6, 2.6, and 2.3, respectively; P =
      0.04), relaxed (2.5, 2.5, and 2.1, respectively; P = 0.02), and content (3.4,
      3.4, and 2.4, respectively, P < 0.01) at postvideo and postsurgery assessments
      compared with mean results at the baseline assessment. The same women were also
      significantly more tense (2.5, 2.0, and 2.0, respectively; P = 0.01), upset (1.6,
      1.1, and 1.1, respectively; P = 0.01), and worried (3.0, 2.0, and 2.0,
      respectively; P = 0.01) at baseline compared with postvideo and postsurgery
      results. Approximately 93% of women believed that other women scheduled to have
      loop excision surgery should also watch the video. CONCLUSIONS: Dissemination of
      culturally sensitive video information minimizes adverse emotional responses
      associated with loop excision procedures before surgery. Such an intervention
      quickly improves the psychological well-being of women eventually subjected to
      surgical management of cervical neoplasia.

PMID- 25856126
TI  - The potential for eliminating chemotherapy in indolent non-Hodgkin lymphoma.

PMID- 25856125
TI  - B-cell receptor pathway inhibitors-rationale and potential.

PMID- 25856127
TI  - The changing landscape in CLL.

PMID- 25856128
TI  - Mantle cell lymphoma: the changing landscape.

PMID- 25856129
TI  - [In real life -- operations inside the EGD].

PMID- 25856130
TI  - The perception of beauty after facial plastic surgery.

PMID- 25856131
TI  - Antireflux metal stent with an antimigration system for distal malignant biliary
      obstruction: a feasibility pilot study.
AB  - An antireflux metal stent (ARMS) for distal malignant biliary obstruction has
      been reported to be useful, but the effectiveness of a flared-end structure to
      prevent migration on ARMS remains unclear. To evaluate the feasibility of a newly
      designed ARMS with both ends flared, 8 patients with covered metal stent
      occlusion due to sludge or food impaction were enrolled. ARMS were placed
      successfully after endoscopic removal of the occluded stents in all patients, and
      no procedure-related complication was observed. The median time to recurrent
      biliary obstruction was 71 days. ARMS occlusion occurred in 3 (38%) patients
      (sludge in 2 patients and hemobilia in 1). ARMS migration occurred in 1 (13%)
      patient. As a late complication, cholecystitis occurred in 1 (13%) patient. In
      conclusion, our newly designed ARMS with an antimigration system was technically
      feasible and safe, and a further investigation is warranted to evaluate the
      effectiveness of the current antimigration system. 

PMID- 25856132
TI  - Weight Loss After Laparoscopic Band-to-Bypass Revision Compared With Primary
      Gastric Bypass: Long-term Outcomes.
AB  - Laparoscopic Roux-en-Y gastric bypass (RYGB) is frequently performed as a salvage
      operation after failed laparoscopic adjustable gastric banding (LAGB). Reports
      about long-term outcomes are lacking. We assessed the long-term outcomes of RYGB
      revision surgery after failed LAGB (study group, n = 44) and compared these
      outcomes with a demographically matched group who underwent primary RYGB (control
      group, n = 82). There were no between-group differences in sex distribution, age,
      or initial weight characteristics. At 2 years after RYGB, the mean DeltaBMI was
      11.8 +/- 5.7 kg/m2 in the study group and 15.6 +/- 4.2 kg/m2 in the control group
      (P = 0.01); the corresponding %EWL values were 57% and 78% (P = 0.005). At 6
      years after RYGB, the mean DeltaBMI was 10 +/- 4.5 kg/m2 in the study group and
      13.6 +/- 5.7 kg/m2 in the control group (P = 0.006); the corresponding %EWL
      values were 53% and 66% (P = 0.04). In conclusion, this study supports the safety
      and favorable weight-loss outcome of LAGB revision to RYGB. However, the results
      are inferior to those of primary RYGB.

PMID- 25856133
TI  - Utilization of High-frequency Mini Probe Ultrasound in the Assessment of Colonic
      Wall Thickness in Patients With Diverticular Disease: A Feasibility Study.
AB  - BACKGROUND: Assessment of diverticular disease (DD) is routinely undertaken by
      colonoscopy and computed tomography (CT) scan. Improvements in high-frequency
      ultrasound have enabled evaluation of the colon wall structure in detail. Our
      objective was to assess ultrasound in measuring colonic wall thickness in DD.
      METHODS: High-frequency 20-MHz ultrasound was undertaken to measure individual
      layer and total colonic wall thickness. Case patients had symptomatic DD. Control
      patients underwent colonoscopy for other reasons. Select patients also underwent
      abdominal CT scan. RESULTS: Thirty-three patients underwent colonoscopic
      ultrasound, 18 with sigmoid diverticula and 15 control patients.Total wall
      thickness was greater in patients with DD, 5.69 mm (1.68) versus 2.61 mm (1.29,
      P<0.0001). Patients with DD had significant thickening in each individual layer
      of the colonic wall measured (each P<0.0001).Greatest differences were in the
      muscularis propria, which was an average of 3.5 times thicker in patients with
      DD. In patients with DD, the segment of colonic wall measured was also thicker,
      with average mid-sigmoid thickness of 23.0 mm (SD 9.6 mm). CONCLUSIONS: Patients
      with DD have increased sigmoid thickness when compared with controls, especially
      the muscularis propria. Unlike CT, ultrasound was also able to identify
      thickening in the mucosa and submucosa.

PMID- 25856134
TI  - Early hospital readmission after laparoscopic cholecystectomy.
AB  - INTRODUCTION: Laparoscopic cholecystectomy (LC) now has become the golden
      standard in the treatment of symptomatic gallstone cholecystitis. AIM: This
      retrospective analysis was conducted to clarify the reasons of early return to
      the hospital after discharge following a procedure like LC that has been
      frequently performed in daily surgical practice. MATERIALS AND METHODS: This
      study covers 586 patients, who were called to follow-ups and thus evaluated, of
      676 patients who had had LCs at Meram Medical School's General Surgery Clinic
      between January 2010 and May 2011. FINDINGS: The rate of representation to the
      hospital during the early phase following LC was found to be 2.4% in our study.
      It was observed that 71% of returning patients had presented to the hospital with
      complaints of abdominal pain. DISCUSSION: We believe that the rate of 2.4% early
      return to the hospital in our series is a bit high when all the complications are
      taken into consideration. This retrospective analysis, however, has shown that
      this rate can further be decreased by taking simple measures.

PMID- 25856135
TI  - Review of complications associated with endoscopic pancreatic cyst-gastrostomy: a
      single-institution experience.
AB  - BACKGROUND: Pancreatic fluid collections can form after episodes of pancreatitis,
      either acute or chronic. The majority will resolve spontaneously but when
      decompression is mandated, endoscopic drainage is the method of choice. However,
      it is not void of complications. METHODS: We retrospectively reviewed the charts
      of 65 patients who underwent endoscopic drainage of pancreatic fluid collections
      in our institution. The primary outcomes examined included the incidence and type
      of complications associated with the endoscopic approach. RESULTS: Endoscopic
      ultrasound was utilized in 86.2% and transgastric approach was used in 81.5% of
      the cases. The complication rate was 17%. Specifically, complications recorded
      were infection (6%), perforation and acute abdomen necessitating surgical
      intervention (4.6%), pneumoperitoneum that was managed nonoperatively (3%), upper
      gastrointestinal bleed in the knife puncture site that resolved spontaneously
      (1.5%), and stent migration (1.5%). One patient died remotely to the endoscopic
      drainage after paracentesis of ascites that resulted in hemorrhagic shock.
      CONCLUSIONS: This study is one of the largest studies reporting the associated
      morbidity and mortality after endoscopic cyst-gastrostomy. Major and minor
      complications occurred at a rate of 17% in our study. Endoscopic approach is a
      safe draining method and should remain the approach of choice for pancreatic
      fluid collection decompression.

PMID- 25856136
TI  - Long-term Outcome of Primary Closure After Laparoscopic Common Bile Duct
      Exploration Combined With Choledochoscopy.
AB  - BACKGROUND: Primary closure after laparoscopic common bile duct exploration
      (LCBDE) is considered to be a safe alternative to T-tube drainage on the basis of
      the short-term outcome. However, little published data exist regarding the
      biliary complications at the long-term follow-up of primary closure versus T-tube
      drainage following LCBDE. Hence, the aim of this study is to assess the long-term
      outcome of primary closure after LCBDE. MATERIALS AND METHODS: This is a
      retrospective study of 142 consecutive patients who underwent LCBDE combined with
      choledochoscopy for CBD stones. After LCBDE, the choledochotomy was closed by
      primary closure (group P) in 91 patients (64.1%) and with T-tube drainage (group
      T) in 51 patients (35.9%). The data on operative outcome and long-term biliary
      complications were compared between the 2 groups. RESULTS: The mean operation
      time was significantly shorter in group P than group T (168.9 +/- 50.1 min for
      group P vs. 198.0 +/- 59.6 min for group T, P = 0.002). The hospital stay was
      significantly shorter in group P than in group T (8.59 +/- 6.0 d for group P vs.
      14.96 +/- 5.4 d for group T, P = 0.001). Postoperative bile leak occurred in 2
      patients (2.2%) in group P and 1 patient (2.0%) in group T. With a mean follow-up
      of 48.8 months, the stone recurrence rate in group P and group T were 4.4% and
      5.9%, respectively (P = 0.722). During the follow-up period, there was no sign of
      biliary stricture or other biliary complications in both groups. CONCLUSIONS: The
      long-term follow-up data on primary closure after LCBDE indicated a low incidence
      of recurrent stones, and no biliary strictures. Thus, primary closure after LCBDE
      with choledochoscopy is considered to be a safe and effective alternative to T
      tube drainage in terms of long-term outcome.

PMID- 25856137
TI  - Commentary Re: Meta-Analysis of Early Endoscopic Retrograde
      Cholangiopancreatography (ERCP) +/- Endoscopic Sphincterotomy (ES) Versus
      Conservative Management for Gallstone Pancreatitis (GSP).

PMID- 25856138
TI  - How to Prevent Trocar-site Hernia? A Totally Atraumatic Endoscopic Mini-IPOM-Plug
      Technique (With Extra-Lightweight Titanium-coated Mesh and Glue).
AB  - BACKGROUND: The trocar-site hernia is a new complication in laparoscopic surgery,
      which is becoming increasingly prevalent. Thus, the search for an efficient
      method of prophylaxis should be prioritized. MATERIALS AND METHODS: We describe a
      new, totally endoscopic technique based on 2 steps, intra-abdominal and parietal:
      (1) a mini-IPOM with an extra-lightweight titanium-coated mesh, fixed
      atraumatically using glue and (2) occlusion of the parietal opening using a small
      plug. RESULTS: In 15 cases, we have not needed to expand the initial aperture,
      performance time was always less than a minute, and we did not encounter any
      added morbidity, pain, local infection, or hernia, over a minimum postoperative
      follow-up period of 6 months. CONCLUSIONS: Our technique for trocar-site closure
      is easy to perform, safe, and not time-consuming. A complete reconstruction is
      achieved of the peritoneal injury (intra-abdominal) and of the parietal route
      created by the trocar (intraparietal). The mesh design and fixation with glue are
      essential for good results.

PMID- 25856139
TI  - An evaluation of the safety of pure laparoscopic hepatectomy in patients with
      liver cirrhosis: investigations including serum albumin and ascites.
AB  - PURPOSE: The purpose of this study was to investigate scientific advantages and
      safety of pure laparoscopic hepatectomy in patients with severe damaged liver and
      cirrhosis. METHODS: Three cohorts were evaluated: group I, patients with severe
      liver damage or cirrhosis (f3-4) who underwent laparoscopic-assisted hepatectomy
      (n=8); group II, patients with severe liver damage or cirrhosis (f3-4) who
      underwent pure laparoscopic hepatectomy (n=10); group III, patients with normal
      liver (f0) who underwent pure laparoscopic hepatectomy (control, n=7). A
      comparison of operative time, blood loss, serum albumin, C-reactive protein,
      duration of hospitalization, duration of postoperative indispensable
      hospitalization, and the duration of ascites drainage was made between the 3
      cohorts. RESULTS: All parameters except for operative time and C-reactive protein
      investigated were significantly worse in group I compared with the other 2
      groups. CONCLUSIONS: In conclusion, pure laparoscopic hepatectomy might be safe
      for patients with damaged liver and cirrhosis.

PMID- 25856140
TI  - Importance of serum amyloid A on the diagnosis of acute appendicitis.

PMID- 25856142
TI  - Intrauterine Tuberculosis Manifesting as Acute Chorioamnionitis: A Case Report
      and Review of the Literature.
AB  - Congenital tuberculosis involving the placenta is an infrequent diagnosis, and
      the typical features of tuberculous placentitis involve a granulomatous reaction,
      reflecting a delayed hypersensitivity immune response in the host. However, the
      first reaction of the placenta to organisms hematogenously transmitted from the
      maternal circulation typically involves the innate immune response, manifesting
      as an acute neutrophilic villitis or intervillositis or both. This acute pattern
      of response to mycobacteria has only been documented rarely. We present a case of
      acute mycobacterial infection occurring in a preterm female with 28-weeks
      gestation, who was delivered by cesarean section because of fetal distress and
      who was subsequently confirmed to have congenital tuberculosis. The placenta
      showed an acute chorioamnionitis associated with acid-fast bacilli consistent
      with Mycobacteria tuberculosis. The mother was found to have a necrotizing
      granulomatous deciduitis, and that was postulated to have resulted in the direct
      spread of mycobacteria to the amniotic cavity. Thus, our case extends the acute
      placental response to mycobacteria to include chorioamnionitis. Although
      extremely rare, mycobacteria should be considered in the differential diagnosis
      of infectious agents causing acute chorioamnionitis, especially in geographic
      areas where tuberculosis is more prevalent. 

PMID- 25856141
TI  - Association between complement C3 and prevalence of fatty liver disease in an
      adult population: a cross-sectional study from the Tianjin Chronic Low-Grade
      Systemic Inflammation and Health (TCLSIHealth) cohort study.
AB  - Activation of the innate immune system plays a key role in the development of
      fatty liver disease (FLD). The complement system is a major humoral component of
      the innate immune response and complement C3 plays a central role, implying that
      C3 may be a powerful predictor or therapeutic target for FLD. However, few
      studies have assessed the association between C3 and FLD in a large population.
      Here we use a cross-sectional study to investigate the link between serum C3
      levels and FLD. Participants were recruited from Tianjin Medical University's
      General Hospital-Health Management Centre. Serum C3 was measured using
      immunoturbidimetry method and FLD was diagnosed by liver ultrasonography.
      Multiple logistic regression analysis was used to examine the association between
      quartiles of C3 and FLD prevalence. The overall prevalence of nonalcoholic fatty
      liver disease (NAFLD) and alcoholic fatty liver disease (AFLD) were 37.3% and
      10.1%, respectively. After adjusting for covariates, the odds ratio of having
      NAFLD or AFLD (only in males) in the fourth quartile of C3 compared with the
      first quartile was 4.13 times greater (95% confidence interval, 2.97-5.77) (trend
      P values < 0.0001) and 2.09 times greater (95% confidence interval, 1.08-4.18)
      (trend P values = 0.02). This is the first study to demonstrate that serum C3
      levels are independently associated with a higher prevalence of NAFLD and AFLD
      (only in males) in an adult population. Further studies are needed to establish a
      causal link and determine the precise role of C3 in FLD. 

PMID- 25856143
TI  - Direct Correlation of Charge Transfer Absorption with Molecular Donor:Acceptor
      Interfacial Area via Photothermal Deflection Spectroscopy.
AB  - Here we show that the charge transfer (CT) absorption signal in bulk
      heterojunction solar cell blends, measured by photothermal deflection
      spectroscopy, is directly proportional to the density of molecular donor:acceptor
      interfaces. Since the optical transitions from the ground state to the
      interfacial CT state are weakly allowed at photon energies below the optical gap
      of both the donor and acceptor, we can exploit the use of this sensitive linear
      absorption spectroscopy for such quantification. Moreover, we determine the
      absolute molar extinction coefficient of the CT transition for an archetypical
      polymer:fullerene interface. The latter is ~100 times lower than the extinction
      coefficient of the donor chromophore involved, allowing us to experimentally
      estimate the transition dipole moment as 0.3 D and the electronic coupling
      between the ground and CT states to be on the order of 30 meV. 

PMID- 25856144
TI  - Contribution of large region joint associations to complex traits genetics.
AB  - A polygenic model of inheritance, whereby hundreds or thousands of weakly
      associated variants contribute to a trait's heritability, has been proposed to
      underlie the genetic architecture of complex traits. However, relatively few
      genetic variants have been positively identified so far and they collectively
      explain only a small fraction of the predicted heritability. We hypothesized that
      joint association of multiple weakly associated variants over large chromosomal
      regions contributes to complex traits variance. Confirmation of such regional
      associations can help identify new loci and lead to a better understanding of
      known ones. To test this hypothesis, we first characterized the ability of
      commonly used genetic association models to identify large region joint
      associations. Through theoretical derivation and simulation, we showed that
      multivariate linear models where multiple SNPs are included as independent
      predictors have the most favorable association profile. Based on these results,
      we tested for large region association with height in 3,740 European participants
      from the Health and Retirement Study (HRS) study. Adjusting for SNPs with known
      association with height, we demonstrated clustering of weak associations (p =
      2x10-4) in regions extending up to 433.0 Kb from known height loci. The
      contribution of regional associations to phenotypic variance was estimated at
      0.172 (95% CI 0.063-0.279; p < 0.001), which compared favorably to 0.129
      explained by known height variants. Conversely, we showed that suggestively
      associated regions are enriched for known height loci. To extend our findings to
      other traits, we also tested BMI, HDLc and CRP for large region associations,
      with consistent results for CRP. Our results demonstrate the presence of large
      region joint associations and suggest these can be used to pinpoint weakly
      associated SNPs. 

PMID- 25856149
TI  - Pleistocene niche stability and lineage diversification in the subtropical spider
      Araneus omnicolor (Araneidae).
AB  - The influence of Quaternary climate oscillations on the diversification of the
      South American fauna is being increasingly explored. However, most of these
      studies have focused on taxa that are endemic to tropical environments, and
      relatively few have treated organisms restricted to subtropical biomes. Here we
      used an integrative phylogeographical framework to investigate the effects of
      these climate events on the ecological niche and genetic patterns of the
      subtropical orb-weaver spider Araneus omnicolor (Araneidae). We analyzed the
      mitochondrial (Cytochrome Oxidase I, COI) and nuclear (Internal Transcribed
      Subunit II, ITS2) DNA of 130 individuals throughout the species' range, and
      generated distribution models in three different climate scenarios [present, Last
      Glacial Maximum (LGM), and Last Interglacial Maximum (LIG)]. Additionally, we
      used an Approximate Bayesian Computation (ABC) approach to compare possible
      demographic scenarios and select the hypothesis that better explains the genetic
      patterns of A. omnicolor. We obtained high haplotype diversity but low nucleotide
      variation among sequences. The population structure and demographic analyses
      showed discrepancies between markers, suggesting male-biased dispersal in the
      species. The time-calibrated COI phylogenetic inference showed a recent
      diversification of lineages (Middle/Late Pleistocene), while the paleoclimate
      modeling indicated niche stability since ~120 Kya. The ABC results agreed with
      the niche models, supporting a panmictic population as the most likely historical
      scenario for the species. These results indicate that A. omnicolor experienced no
      niche or population reductions during the Late Pleistocene, despite the intense
      landscape modifications that occurred in the subtropical region, and that other
      factors beside LGM and LIG climate oscillations might have contributed to the
      demographic history of this species. This pattern may be related to the high
      dispersal ability and wide environmental tolerance of A. omnicolor, highlighting
      the need for more phylogeographical studies with invertebrates and other
      generalist taxa, in order to understand the effects of Quaternary climate changes
      on Neotropical biodiversity. 

PMID- 25856150
TI  - The association of ethnic minority density with late entry into antenatal care in
      the Netherlands.
AB  - In the Netherlands, non-Western ethnic minority women make their first antenatal
      visit later than native Dutch women. Timely entry into antenatal care is
      important as it provides the opportunity for prenatal screening and the detection
      of risk factors for adverse pregnancy outcomes. In this study we explored whether
      women's timely entry is influenced by their neighborhood. Moreover, we assessed
      whether ethnic minority density (the proportion of ethnic minorities in a
      neighborhood) influences Western and non-Western ethnic minority women's chances
      of timely entry into care differently. We hypothesized that ethnic minority
      density has a protective effect against non-Western women's late entry into care.
      Data on time of entry into care and other individual-level characteristics were
      obtained from the Netherlands Perinatal Registry (2000-2008; 97% of all
      pregnancies). We derived neighborhood-level data from three other national
      databases. We included 1,137,741 pregnancies of women who started care under
      supervision of a community midwife in 3422 neighborhoods. Multi-level logistic
      regression was used to assess the associations of individual and neighborhood
      level determinants with entry into antenatal care before and after 14 weeks of
      gestation. We found that neighborhood characteristics influence timely entry
      above and beyond individual characteristics. Ethnic minority density was
      associated with a higher risk of late entry into antenatal care. However, our
      analysis showed that for non-Western women, living in high ethnic minority
      density areas is less detrimental to their risk of late entry than for Western
      women. This means that a higher proportion of ethnic minority residents has a
      protective effect on non-Western women's chances of timely entry into care. Our
      results suggest that strategies to improve timely entry into care could seek to
      create change at the neighborhood level in order to target individuals likely of
      entering care too late. 

PMID- 25856151
TI  - Unraveling the intricate nexus of molecular mechanisms governing rice root
      development: OsMPK3/6 and auxin-cytokinin interplay.
AB  - The root system is an imperative component of a plant, involved in water and
      nutrient acquisition from the soil. Any subtle change in the root system may lead
      to drastic changes in plant productivity. Both auxin and cytokinin are implicated
      in regulating various root developmental aspects. One of the major signaling
      cascades facilitating various hormonal and developmental allocations is the
      Mitogen Activated Protein Kinase (MAPK) cascade. Innumerable efforts have been
      made to unravel the complex nexus involved in rice root development. In spite of
      a plethora of studies, a comprehensive study aiming to decipher the plausible
      cross-talk of MAPK signaling module with auxin and cytokinin signaling components
      in rice is missing. In the present study, extensive phenomics analysis of
      different stages of rice roots; transcript profiling by qRT-PCR of entire gene
      family of MAPK, MAPKK and PIN genes; as well as protein level and activity of
      potential MAPKs was investigated using western and immuno kinase assays both on
      auxin and cytokinin treatment. The above study led to the identification of
      various novel rice root specific phenotypic traits by using GiA roots software
      framework. High expression profile of OsMPK3/6, OsMKK4/5 and OsPIN 1b/9 and their
      marked transcript level modulation in response to both auxin and cytokinin was
      observed. Finally, the protein levels and activity assay further substantiated
      our present findings. Thus, OsMPK3/6-OsMKK4/5 module is elucidated as the
      putative, key player in auxin-cytokinin interaction augmenting their role by
      differentially regulating the expression patterns of OsPIN 1b/9 in root
      development in rice. 

PMID- 25856152
TI  - Lipid structural effects of oral administration of methylphenidate in Drosophila
      brain by secondary ion mass spectrometry imaging.
AB  - We use time-of-flight secondary ion mass spectrometry (TOF-SIMS) imaging to
      investigate the effects of orally administrated methylphenidate on lipids in the
      brain of Drosophila melanogaster (fruit fly), a major invertebrate model system
      in biological study and neuroscience. TOF-SIMS imaging was carried out using a
      recently designed high energy 40 keV Ar4000(+) gas cluster ion gun which
      demonstrated improved sensitivity for intact lipids in the fly brain compared to
      the 40 keV C60(+) primary ion gun. In addition, correlation of TOF-SIMS and SEM
      imaging on the same fly brain showed that there is specific localization that is
      related to biological functions of various biomolecules. Different lipids
      distribute in different parts of the brain, central brain, optical lobes, and
      proboscis, depending on the length of the carbon chain and saturation level of
      fatty acid (FA) branches. Furthermore, data analysis using image principal
      components analysis (PCA) showed that methylphenidate dramatically affected both
      the distribution and abundance of lipids and their derivatives, particularly
      fatty acids, diacylglycerides, phosphatidylcholine, phosphatidylethanolamine, and
      phosphatidylinositol in the fly brains. Our approach using TOF-SIMS imaging
      successfully visualizes the effects of methylphenidate on the chemical structure
      of the fly brain. 

PMID- 25856153
TI  - All-printed stretchable electrochemical devices.
AB  - The fabrication and characterization of all-printed, inexpensive, stretchable
      electrochemical devices is described. These devices are based on specially
      engineered inks that can withstand severe tensile strain, as high as 100%,
      without any significant effect on their electrochemical properties. Such
      stretchable electrochemical devices should be attractive for diverse sensing and
      energy applications. 

PMID- 25856154
TI  - Experimental and computational analysis of composite ankle-foot orthosis.
AB  - Carbon fiber (CF) ankle-foot orthoses (AFOs) can improve gait by increasing ankle
      plantar-flexor power and improving plantar-flexor ankle joint moment and energy
      efficiency compared with posterior leaf spring AFOs made of thermoplastic.
      However, fabricating a CF AFO to optimize the performance of the individual user
      may require multiple AFOs and expensive fabrication costs. Finite element
      analysis (FEA) models were developed to predict the mechanical behavior of AFOs
      in this study. Three AFOs, two made of CF composite material and one made of
      thermoplastic material, were fabricated and then mechanically tested to produce
      force-displacement data. The FEA models were validated by comparing model
      predictions with mechanical testing data performed under the same loading and
      boundary conditions. The actual mechanical testing demonstrated that CF performs
      better than thermoplastic. The simulation results showed that FEA models produced
      accurate predictions for both types of orthoses. The relative error of the energy
      return ratio predicted by the CF AFO FEA model developed in this study is less
      than 3%. We conclude that highly accurate FEA models will allow orthotists to
      improve CF AFO fabrication without wasting resources (time and money) on trial
      and error fabrications that are expensive and do not consistently improve AFO and
      user performance. 

PMID- 25856157
TI  - Safety and efficacy of a patient-controlled bladder management system for
      treating urinary retention in men.
AB  - AIMS: The CymActiveTM Bladder Management System (BMS) is a self-retaining,
      intraurethral catheter with a patient-controlled magnetic valve that allows
      cyclical bladder filling and emptying, without external appliances. We determined
      the safety and efficacy of the BMS in men with urinary retention who required
      catheterization for more than 7 days. METHODS: Men requiring continuous drainage,
      bladder capacity less than 300 ml, history of prostatic or urethral surgery, or
      urethral length outside of defined limits, were excluded. Data were collected
      from patient diaries and weekly visits during catheterization for up to 30 days.
      The primary composite endpoint assessed four outcomes: placement, post-void
      residual volume (PVR) of 75 ml or less, adverse device-related events requiring
      early removal, and removal. RESULTS: Nine of 23 patients met all four criteria:
      eight of 18 non-neurogenic (7/11 prior Foley users and 1/7 without Foley
      experience) and one of five neurogenic spinal cord injury (SCI) patients.
      Secondary outcomes in non-neurogenic patients included: 17/18 successful
      insertions; of these, 16/17 average PVR of 75 ml; successful valve openings and
      closings >= 95% of more than 1,400 voids; and minimal leakage. Four of five SCI
      patients discontinued within 7 days. Cystourethroscopy after removal revealed no
      marked inflammation or mucosal changes. CONCLUSIONS: This pilot study
      demonstrated the BMS is potentially useful, convenient, and safe for appropriate
      patients. A follow-up study will better define the characteristics of patients
      who benefit from this device and examine whether the use of antimuscarinic agents
      improves outcomes. Neurourol. Urodynam. 35:630-635, 2016. (c) 2015 Wiley
      Periodicals, Inc.

PMID- 25856158
TI  - Enhanced gene silencing through human serum albumin-mediated delivery of
      polyethylenimine-siRNA polyplexes.
AB  - Small interfering RNA (siRNA) targeted therapeutics (STT) offers a compelling
      alternative to tradition medications for treatment of genetic diseases by
      providing a means to silence the expression of specific aberrant proteins,
      through interference at the expression level. The perceived advantage of siRNA
      therapy is its ability to target, through synthetic antisense oligonucleotides,
      any part of the genome. Although STT provides a high level of specificity, it is
      also hindered by poor intracellular uptake, limited blood stability, high
      degradability and non-specific immune stimulation. Since serum proteins has been
      considered as useful vehicles for targeting tumors, in this study we investigated
      the effect of incorporation of human serum albumin (HSA) in branched
      polyethylenimine (bPEI)-siRNA polyplexes in their internalization in epithelial
      and endothelial cells. We observed that introduction of HSA preserves the
      capacity of bPEI to complex with siRNA and protect it against extracellular
      endonucleases, while affording significantly improved internalization and
      silencing efficiency, compared to bPEI-siRNA polyplexes in endothelial and
      metastatic breast cancer epithelial cells. Furthermore, the uptake of the HSA
      bPEI-siRNA ternary polyplexes occurred primarily through a caveolae-mediated
      endocytosis, thus providing evidence for a clear role for HSA in polyplex
      internalization. These results provide further impetus to explore the role of
      serum proteins in delivery of siRNA. 

PMID- 25856159
TI  - Amelioration of age-dependent increase in oxidative stress markers in male mice
      by extract of Potentilla fulgens.
AB  - OBJECTIVE: To investigate the effect of Potentilla fulgens extract on lipid
      peroxidation and antioxidant status in male mice as a function of age. METHODS:
      Eighteen-month-old Swiss albino male mice were administered the dichloromethane
      methanol extract of P. fulgens (250 mg/kg b.w.) on alternate days via
      intraperitoneal route for a period of 14 days. Lipid peroxidation and activities
      of catalase (CAT) and glutathione peroxidase (GPx1) in liver and kidney were
      measured and serum oxygen radical absorbance capacity (ORAC) assay was estimated.
      Phytochemical analysis of P. fulgens extract using high performance thin layer
      chromatography (HPTLC) was carried out with gallic acid, quercetin, catechin, and
      epicatechin as markers. RESULTS: Significant increase in level of thiobarbituric
      acid-reactive substances (TBARS), decreased GPx1, and CAT activities as well as
      reduction in ORAC were observed in 18-month-old mice as compared to that of 2
      month-old mice. Treatment with P. fulgens extract significantly lowered TBARS
      level, ameliorated CAT, and GPx1 activities in liver and kidney and improved
      serum ORAC in aging mice. HPTLC studies revealed well resolved bands of P.
      fulgens extract containing epicatechin and catechin. DISCUSSION: This study
      showed that P. fulgens is a potent antioxidative agent, which can emerge as a
      promising candidate in alleviating the age-associated oxidative stress and
      related diseases.

PMID- 25856160
TI  - Longitudinal effects of menopausal hormone treatments on platelet characteristics
      and cell-derived microvesicles.
AB  - Activated platelets serve as a catalyst for thrombin generation and a source of
      vasoactive and mitogenic factors affecting vascular remodeling. Oral menopausal
      hormone treatments (MHT) may carry greater thrombotic risk than transdermal
      products. This study compared effects of oral and transdermal MHT on platelet
      characteristics, platelet proteins, and platelet-derived microvesicles (MV) in
      recently menopausal women. Platelets and MV were prepared from blood of a subset
      of women (n = 117) enrolled in the Kronos Early Estrogen Prevention Study prior
      to and after 48 months of treatment with either oral conjugated equine estrogen
      (0.45 mg/day), transdermal 17beta-estradiol (50 ug/day), each with intermittent
      progesterone (200 mg/day for 12 days a month), or placebo pills and patch.
      Platelet count and expression of platelet P-selectin and fibrinogen receptors
      were similar across groups. An aggregate measure of 4-year change in vasoactive
      and mitogenic factors in platelet lysate, by principle component analysis,
      indicated significantly lower values in both MHT groups compared to placebo.
      Increases in numbers of tissue factor positive and platelet-derived MV were
      significantly greater in the transdermal compared to placebo group. MHT was
      associated with significantly reduced platelet content of vasoactive and
      mitogenic factors representing a potential mechanism by which MHT may affect
      vascular remodeling. Various hormonal compositions and doses of MHT could
      differentially regulate nuclear transcription in bone marrow megakaryocytes and
      non-genomic pathways in circulating platelets thus determining numbers and
      characteristics of circulating MV. Thrombotic risk associated with oral MHT most
      likely involves liver-derived inflammatory/coagulation proteins rather than
      circulating platelets per se.

PMID- 25856161
TI  - Age-related changes in sentence production abilities and their relation to
      working-memory capacity: evidence from a verb-final language.
AB  - OBJECTIVES: This study investigated the best predictor to capture age-related
      changes in passive-sentence production using a constrained sentence-production
      paradigm and explored the role of working-memory capacity in relation to the task
      demands of the sentence-production tasks. METHODS: A total of 60 participants
      participated in the study ranging in age from 21 to 86. All were administered a
      syntactic-priming and a sentence-completion task under either canonical or
      noncanonical word-order conditions. RESULTS: Age was significantly and negatively
      correlated with sentence-production tasks, and the most demanding condition with
      a noncanonical word order under the syntactic priming paradigm was the best
      predictor of aging. Working-memory capacity was significantly and positively
      correlated with all conditions, but the significant correlation remained only for
      the most demanding condition (the priming task with a noncanonical word order)
      after controlling for age. DISCUSSION: Sentence-production abilities were
      vulnerable to aging, and these effects manifested most clearly when the task
      demands were high enough to tax individuals' cognitive capacity. Working-memory
      capacity partially accounted for age-related changes in sentence-production
      abilities.

PMID- 25856162
TI  - Methionine biosynthesis is essential for infection in the rice blast fungus
      Magnaporthe oryzae.
AB  - Methionine is a sulfur amino acid standing at the crossroads of several
      biosynthetic pathways. In fungi, the last step of methionine biosynthesis is
      catalyzed by a cobalamine-independent methionine synthase (Met6, EC 2.1.1.14). In
      the present work, we studied the role of Met6 in the infection process of the
      rice blast fungus, Magnaporthe oryzae. To this end MET6 null mutants were
      obtained by targeted gene replacement. On minimum medium, MET6 null mutants were
      auxotrophic for methionine. Even when grown in presence of excess methionine,
      these mutants displayed developmental defects, such as reduced mycelium
      pigmentation, aerial hypha formation and sporulation. They also displayed
      characteristic metabolic signatures such as increased levels of cysteine,
      cystathionine, homocysteine, S-adenosylmethionine, S-adenosylhomocysteine while
      methionine and glutathione levels remained unchanged. These metabolic
      perturbations were associated with the over-expression of MgCBS1 involved in the
      reversed transsulfuration pathway that metabolizes homocysteine into cysteine and
      MgSAM1 and MgSAHH1 involved in the methyl cycle. This suggests a physiological
      adaptation of M. oryzae to metabolic defects induced by the loss of Met6, in
      particular an increase in homocysteine levels. Pathogenicity assays showed that
      MET6 null mutants were non-pathogenic on both barley and rice leaves. These
      mutants were defective in appressorium-mediated penetration and invasive
      infectious growth. These pathogenicity defects were rescued by addition of
      exogenous methionine and S-methylmethionine. These results show that M. oryzae
      cannot assimilate sufficient methionine from plant tissues and must synthesize
      this amino acid de novo to fulfill its sulfur amino acid requirement during
      infection. 

PMID- 25856163
TI  - Tropical rain forest structure, tree growth and dynamics along a 2700-m
      elevational transect in Costa Rica.
AB  - Rapid biological changes are expected to occur on tropical elevational gradients
      as species migrate upslope or go extinct in the face of global warming. We
      established a series of 9 1-ha plots in old-growth tropical rainforest in Costa
      Rica along a 2700 m relief elevational gradient to carry out long-term monitoring
      of tropical rain forest structure, dynamics and tree growth. Within each plot we
      mapped, identified, and annually measured diameter for all woody individuals with
      stem diameters >10 cm for periods of 3-10 years. Wood species diversity peaked at
      400-600 m and decreased substantially at higher elevations. Basal area and stem
      number varied by less than two-fold, with the exception of the 2800 m cloud
      forest summit, where basal area and stem number were approximately double that of
      lower sites. Canopy gaps extending to the forest floor accounted for <3% of
      microsites at all elevations. Height of highest crowns and the coefficient of
      variation of crown height both decreased with increasing elevation. Rates of
      turnover of individuals and of stand basal area decreased with elevation, but
      rates of diameter growth and stand basal area showed no simple relation to
      elevation. We discuss issues encountered in the design and implementation of this
      network of plots, including biased sampling, missing key meteorological and
      biomass data, and strategies for improving species-level research. Taking full
      advantage of the major research potential of tropical forest elevational
      transects will require sustaining and extending ground based studies,
      incorporation of new remotely-sensed data and data-acquisition platforms, and new
      funding models to support decadal research on these rapidly-changing systems. 

PMID- 25856164
TI  - Natural selection causes adaptive genetic resistance in wild emmer wheat against
      powdery mildew at "Evolution Canyon" microsite, Mt. Carmel, Israel.
AB  - BACKGROUND: "Evolution Canyon" (ECI) at Lower Nahal Oren, Mount Carmel, Israel,
      is an optimal natural microscale model for unraveling evolution in action
      highlighting the basic evolutionary processes of adaptation and speciation. A
      major model organism in ECI is wild emmer, Triticum dicoccoides, the progenitor
      of cultivated wheat, which displays dramatic interslope adaptive and speciational
      divergence on the tropical-xeric "African" slope (AS) and the temperate-mesic
      "European" slope (ES), separated on average by 250 m. METHODS: We examined 278
      single sequence repeats (SSRs) and the phenotype diversity of the resistance to
      powdery mildew between the opposite slopes. Furthermore, 18 phenotypes on the AS
      and 20 phenotypes on the ES, were inoculated by both Bgt E09 and a mixture of
      powdery mildew races. RESULTS: In the experiment of genetic diversity, very
      little polymorphism was identified intra-slope in the accessions from both the AS
      or ES. By contrast, 148 pairs of SSR primers (53.23%) amplified polymorphic
      products between the phenotypes of AS and ES. There are some differences between
      the two wild emmer wheat genomes and the inter-slope SSR polymorphic products
      between genome A and B. Interestingly, all wild emmer types growing on the south
      facing slope (SFS=AS) were susceptible to a composite of Blumeria graminis, while
      the ones growing on the north-facing slope (NFS=ES) were highly resistant to
      Blumeria graminis at both seedling and adult stages. CONCLUSION/SIGNIFICANCE:
      Remarkable inter-slope evolutionary divergent processes occur in wild emmer
      wheat, T. dicoccoides at EC I, despite the shot average distance of 250 meters.
      The AS, a dry and hot slope, did not develop resistance to powdery mildew,
      whereas the ES, a cool and humid slope, did develop resistance since the disease
      stress was strong there. This is a remarkable demonstration in host-pathogen
      interaction on how resistance develops when stress causes an adaptive result at a
      micro-scale distance.

PMID- 25856165
TI  - Medical Honey and Silver Dressings Do Not Interfere with Each Other's Key
      Functional Attributes.
AB  - OBJECTIVE: This study sought to determine whether silver-containing dressings and
      medical-grade honey gel interfere with one another in measurable ways. MATERIALS
      AND METHODS: Dressings applied together in clinical use were tested using in
      vitro and ex vivo methods to determine whether the combined modalities maintain
      their individual properties. In order to determine if the presence of silver
      dressings interfere with honey's osmotic strength, which is a key physical
      property of medical honey, changes in honey's 2 primary sugars were measured, as
      well as changes in its overall osmotic strength. Finally, the antibacterial
      barrier activity of the dressings were tested individually and in honey/silver
      pairs in 2 in vitro models with 2 clinical strains of bacteria. RESULTS: The data
      demonstrate that honey with silver dressings resulted in an increased osmolarity,
      since both the concentration of the 2 primary sugars in honey as well as its
      overall osmolarity increased. The data also demonstrate that the in vitro
      antibacterial barrier activity seen with silver-containing dressings does not
      decrease with the addition of medical honey and in some instances increased.
      CONCLUSION: Altogether, these data suggest that these 2 classes of dressings do
      not interfere with each other. Clinical evidence is still required to fully
      validate these findings.

PMID- 25856166
TI  - Effects of circadian rhythm disorders on wound healing and strength of bowel
      anastomosis in rats.
AB  - INTRODUCTION: Many body systems, especially the immune system, are affected by
      circadian rhythm disorders (CRDs). This study investigated the effects of shift
      lag on wound healing and bowel anastomosis in rats. MATERIALS AND METHODS: Forty
      five rats were randomly divided into 3 groups: placebo, control, and
      experimental. Circadian rhythm was disturbed with altered light/dark cycles.
      Colon anastomosis was performed in rats with and without disturbed circadian
      rhythms. Serum melatonin levels and bowel anastomosis bursting pressures were
      measured. Tissue samples were used to measure tissue hydroxyproline levels and
      for histological assessment. RESULTS: In the groups with an altered circadian
      rhythm, the bowel bursting pressures, tissue hydroxyproline levels, and fibrosis
      were greater than the control group. CONCLUSION: This study found that a CRD,
      simulated by altered light/dark cycles, positively affected the anastomotic
      bursting pressure. This suggests that cytokines such as interleukin (IL)-1, IL-6,
      transforming growth factor alpha, and stress hormones affect fibroblasts and
      thereby increase collagen synthesis in the proliferative phase. More studies are
      necessary to understand the effects of CRDs.    .

PMID- 25856167
TI  - Visualization of Tumor Necrosis Factor-alpha Distributions Within Pressure Ulcer
      Tissue Using the Wound Blotting Method: A Case Report and Discussion.
AB  - Wound blotting can be used to visualize the protein distribution on a wound bed
      through protein collection by attaching a nitrocellulose membrane to the wound
      surface. This study checked for consistency between the protein distributions
      determined by wound blotting and those determined by removal of the tissue. A
      patient who was planning to undergo surgical debridement of an ulcer in the
      sacral region that was caused by lying down for a long period after a cerebral
      hemorrhage was recruited in Fujisawa City Hospital, Kanagawa, Japan. Wound
      blotting was performed just prior to surgical debridement and the debrided tissue
      embedded in paraffin. The ulcer, which had a 2.9 cm major axis, was divided into
      20 areas approximately 0.35 cm2 each, and the consistency of tumor necrosis
      factor-alpha positivity between the wound blotting samples and tissue sections
      was examined in each area. The sensitivity and specificity of wound blotting were
      89% and 82%, respectively. This wound blotting method noninvasively revealed the
      protein distributions within the wound tissue. 

PMID- 25856168
TI  - Frequency dependant topological alterations of intrinsic functional connectome in
      major depressive disorder.
AB  - Major depressive disorder is associated with aberrant topological organizations
      of brain networks. However, whether this aberrance is shown in broader frequency
      bands or in a specific frequency band remains unknown. Fifty patients and fifty
      gender, age and education matched normal controls underwent resting state
      functional magnetic resonance imaging. Frequency dependent topological measures
      based on graph theory were calculated from wavelet decomposed resting state
      functional brain signals. In the specific frequency band of 0.03-0.06 Hz, the
      clustering coefficient and the global efficiency were reduced while the
      characteristic path length was increased. Furthermore, patients showed aberrant
      nodal centralities in the default mode network, executive network and occipital
      network. Network based statistical analysis revealed system-wise topological
      alterations in these networks. The finding provides the first systematic evidence
      that depression is associated with frequency specific global and local
      topological disruptions and highlights the importance of frequency information in
      investigating major depressive disorders.

PMID- 25856169
TI  - A pilot randomized trial of high-dose caffeine therapy in preterm infants.
AB  - BACKGROUND: Standard-dose caffeine improves white matter microstructural
      development assessed by diffusion magnetic resonance imaging (MRI). We
      hypothesized that early high-dose caffeine would result in further improvement in
      white matter microstructural development. METHODS: Seventy-four preterm infants
      (<=30 wk gestational age) were randomly assigned to either a high (80 mg/kg i.v.)
      or standard (20 mg/kg i.v.) loading dose of caffeine citrate in the first 24 h of
      life. MRI and neurobehavioral testing were undertaken at term equivalent age.
      Infants returned at 2 y of age for developmental testing. RESULTS: Clinical
      characteristics were similar between groups, with the exception of higher
      maternal age in the high-dose caffeine group. There was an increased incidence of
      cerebellar hemorrhage in infants randomized to high-dose caffeine (36 vs. 10%, P
      = 0.03). Infants in the high-dose caffeine group also demonstrated more
      hypertonicity (P = 0.02) and more deviant neurologic signs (P = 0.04) at term
      equivalent age. Diffusion measures at term equivalent age and developmental
      outcomes at 2 y of age did not differ between groups. CONCLUSION: Preterm infants
      randomized to early high-dose caffeine had a higher incidence of cerebellar
      injury with subsequent alterations in early motor performance. The results of
      this pilot trial discourage a larger randomized controlled trial.

PMID- 25856170
TI  - Why do children decide not to participate in clinical research: a quantitative
      and qualitative study.
AB  - BACKGROUND: More pediatric drug trials are needed, but although specific
      pediatric regulations warrant safety, recruitment of children for these trials
      remains one of the main difficulties. Therefore, we investigated potential
      determining factors of nonparticipation in clinical research, in order to
      optimize research participation of children by recommending improved recruitment
      strategies. METHODS: Between 1 January 2012 and 1 January 2014, we performed a
      prospective study among161 pediatric patients, aged 6 to 18 y, who were eligible
      for clinical research. We quantitatively analyzed the association of potential
      explanatory variables (e.g., age, cognitive development, experience, ethnicity)
      with nonparticipation and qualitatively analyzed interviews on reasons for
      nonparticipation. RESULTS: Sixty percent of the children did not participate in
      the research project on offer (39% decided not to participate, 21% were
      indecisive). Lower age, less disease experience, and less complex research with
      lower risk were predictive for not participating. Time constraint and extra
      burden were expressed as decisive reasons for not participating. CONCLUSIONS:
      Strategies to optimize research participation should be aimed at younger children
      and their families, who are logistically challenged and unfamiliar with health
      care and research. Recommendations include informing pediatric patients and their
      families of the value of research; minimizing logistic burdens; and improving
      accessibility.

PMID- 25856171
TI  - Block copolymer self-assembly for nanophotonics.
AB  - The ability to control and modulate the interaction of light with matter is
      crucial to achieve desired optical properties including reflection, transmission,
      and selective polarization. Photonic materials rely upon precise control over the
      composition and morphology to establish periodic interactions with light on the
      wavelength and sub-wavelength length scales. Supramolecular assembly provides a
      natural solution allowing the encoding of a desired 3D architecture into the
      chemical building blocks and assembly conditions. The compatibility with solution
      processing and low-overhead manufacturing is a significant advantage over more
      complex approaches such as lithography or colloidal assembly. Here we review
      recent advances on photonic architectures derived from block copolymers and
      highlight the influence and complexity of processing pathways. Notable examples
      that have emerged from this unique synthesis platform include Bragg reflectors,
      antireflective coatings, and chiral metamaterials. We further predict expanded
      photonic capabilities and limits of these approaches in light of future
      developments of the field. 

PMID- 25856173
TI  - Highlights in T-cell lymphoma From the 2013 American Society of Hematology Annual
      Meeting and Exposition.

PMID- 25856172
TI  - Adjuvant chemotherapy for elderly patients (aged 70 or older) with gastric cancer
      after a gastrectomy with D2 dissection: A single center experience in Korea.
AB  - AIMS: Adjuvant chemotherapy is recommended for gastric cancer after a gastrectomy
      with D2 dissection. However, its survival benefit in elderly patients is unclear.
      Here we investigated the use of adjuvant chemotherapy in patients >=70 years old
      with stage II or III gastric cancer. METHODS: Patients >=70 years old diagnosed
      with stage II or III gastric cancer at Ulsan University Hospital were identified.
      A retrospective analysis of electronic and paper patient records was performed.
      RESULTS: From 2008 to 2012, 277 patients >=70 years old underwent gastrectomy
      with D2 dissection. Of these patients, 94 were pathologically diagnosed with
      stage II or III; 55 of these patients (58.5%) received adjuvant chemotherapy and
      39 received regular checkups without chemotherapy. Fluoropyrimidine-alone
      regimens, including TS-1 composed of tegafur, gimestat and otastat potassium (n =
      26) and doxifluridine (n = 22), were more commonly used than fluoropyrimidine
      platinum combination regimens (n = 7). With a median follow-up of 30.9 (range 0.8
      65.5) months, the median relapse-free survival of patients with adjuvant
      chemotherapy or regular follow-up only was 35.5 and 20.4 months, respectively (P
      = 0.030). Multivariate analysis revealed that adjuvant chemotherapy is associated
      with longer relapse-free survival (hazard ratio 0.50; 95% confidence interval
      0.27-0.96). There was a trend toward an improved overall survival in the adjuvant
      chemotherapy group compared with the follow-up only group (P = 0.242).
      CONCLUSIONS: Although well-designed prospective studies are required, adjuvant
      chemotherapy may confer a potential survival benefit in elderly patients (aged 70
      or older) with stage II or III gastric cancer after a gastrectomy with D2
      dissection.

PMID- 25856174
TI  - Highlights in T-cell lymphoma From the 2013 American Society of Hematology Annual
      Meeting and Exposition: commentary.

PMID- 25856175
TI  - Procurement strategies for combined multiorgan and composite tissues for
      transplantation.
AB  - PURPOSE OF REVIEW: The purpose of this article is to identify the unique aspects
      of combined multiorgan and vascularized composite allograft (VCA) procurement
      from deceased donors and outline the steps essential for success. RECENT
      FINDINGS: Transplantation of nonsolid organ composite tissues is becoming a
      viable option for reconstruction of massive tissue defects. With the United
      Network for Organ Sharing designation of VCAs as organs, placing them under the
      domain of the Organ Procurement and Transplantation Network, a systematic method
      for combined solid organ and VCA procurement is required. Several centers have
      reported experience with successful procurement strategies including sequential
      and simultaneous retrievals. The published literature describing donor screening,
      sequence of procurement with relation to solid organs and allocation is reviewed.
      SUMMARY: With the 2013 classification of VCAs as organs, the Organ Procurement
      and Transplantation Network and United Network for Organ Sharing are better
      suited to aligning procurement and allocation policies. As VCA transplantation
      becomes more commonplace, protocol guidelines will ensure smooth integration with
      existing procurement infrastructure.

PMID- 25856176
TI  - Parental live liver donation: psychosocial considerations in the decision to
      donate.
AB  - PURPOSE OF REVIEW: Live donor liver transplantation is a treatment option for
      patients in need of orthotopic liver transplantation to mitigate the organ
      shortage from deceased donors. The long-term outcomes for pediatric recipients
      from live liver donors are excellent, and parents commonly are the ones seeking
      donation to save their child from irreversible liver failure. Although live
      donors go through a careful medical and psychosocial evaluation to ensure the
      benefits of donation outweigh the risks, parental live liver donation poses
      unique challenges due to the biological and emotional relationships with the
      child. This article highlights specific psychosocial considerations for parental
      live liver donors. RECENT FINDINGS: There is limited research regarding the
      psychosocial evaluation and outcomes for live liver donors. Some literature
      suggests the need for standard criteria regarding the psychosocial evaluation of
      donors because of the risks. However, there are positive benefits with donation,
      such as improved emotional quality of life for adult to pediatric donors, and the
      possible benefits should be considered. SUMMARY: Live liver donation is an
      appealing alternative treatment option, particularly in the pediatric population,
      in which outcomes are generally positive and medical risk to donor is less than
      adult-to-adult donation. For parental donors, special consideration should be
      given to the informed consent and the decision-making process, psychological
      health, and presence of substance use when weighing the risk versus protective
      factors for donors.

PMID- 25856177
TI  - Organ preservation review: history of organ preservation.
AB  - PURPOSE OF REVIEW: To summarize the history of organ preservation and place into
      this context the current trends in preservation. RECENT FINDINGS: Multiple large
      retrospective studies have analyzed cold preservation solutions in an attempt to
      determine superiority with largely negative results. Experimental and some
      clinical studies have examined machine perfusion of procured grafts, in both
      hypothermic and normothermic contexts with variable, but promising, results.
      Lastly, there are experimental efforts to evaluate mesenchymal stem cell therapy
      on rehabilitation of marginal donor organs. SUMMARY: New trends in organ
      preservation may soon translate into more efficient use of the limited donor
      pool.

PMID- 25856178
TI  - Whole kidney engineering for clinical translation.
AB  - PURPOSE OF REVIEW: Renal transplantation is currently the only definitive
      treatment for end-stage renal disease; however, this treatment is severely
      limited by the shortage of implantable kidneys. To address this shortcoming,
      development of an engineered, transplantable kidney has been proposed. Although
      current advances in engineering kidneys based on decellularization and
      recellularization techniques have offered great promises for the generation of
      functional kidney constructs, most studies have been conducted using rodent
      kidney constructs and short-term in-vivo evaluation. Toward clinical translations
      of this technique, several limitations need to be addressed. RECENT FINDINGS:
      Human-sized renal scaffolds are desirable for clinical application, and the
      fabrication is currently feasible using native porcine and discarded human
      kidneys. Current progress in stem cell biology and cell culture methods have
      demonstrated feasibility of the use of embryonic stem cells, induced pluripotent
      stem cells, and primary renal cells as clinically relevant cell sources for the
      recellularization of renal scaffolds. Finally, approaches to long-term
      implantation of engineered kidneys are under investigation using antithrombogenic
      strategies such as functional reendothelialization of acellular kidney matrices.
      SUMMARY: In the field of bioengineering, whole kidneys have taken a number of
      important initial steps toward clinical translations, but many challenges must be
      addressed to achieve a successful treatment for the patient with end-stage renal
      disease.

PMID- 25856179
TI  - Kidney regeneration from human induced pluripotent stem cells.
AB  - PURPOSE OF REVIEW: Human induced pluripotent stem cells (iPSCs) and embryonic
      stem cells (ESCs) are potential unlimited cell sources for renal cells in
      regenerative medicine. This review highlights recent advance in the directed
      differentiation of human iPSCs into kidney lineages and discusses the remaining
      challenges to generate functional or mature renal cells from human iPSCs. RECENT
      FINDINGS: Recently, directed differentiation methods from human iPSCs/ESCs into
      embryonic renal progenitor cells, such as those included in metanephric
      mesenchyme and ureteric bud, that mimic embryonic development have been reported.
      These studies show the developmental potential of progenitor cells by forming
      renal tubule-like or glomerulus-like structures in vitro. However, it has not
      been verified whether the physiological functions of the induced progenitors are
      equivalent to their in-vivo counterparts. The establishment of definitive marker
      genes for kidney lineages and functional assay systems is essential for the
      verification. Such achievement is needed before kidney regeneration can provide
      cell replacement therapy, reliable disease models and elucidation of the
      mechanisms of kidney development. SUMMARY: In conclusion, this review outlines
      milestones in directed differentiation methods for functional renal cell types
      from human iPSCs toward clinical application and practical use.

PMID- 25856180
TI  - Generating a self-organizing kidney from pluripotent cells.
AB  - PURPOSE OF REVIEW: Recent studies on the directed differentiation of human
      pluripotent stem cells report tissue self-organization in vitro such that
      multiple component cell types arise in concert and arrange with respect to each,
      thereby recapitulating the morphogenetic events typical for that organ. Such self
      organization has generated pituitary, optic cup, liver, brain, intestine, stomach
      and now kidney. Here, we will describe the cell types present within the self
      organizing kidney, how these signal to each other to form a kidney organoid and
      the potential applications of kidney organoids. RECENT FINDINGS: Protocols for
      the directed differentiation of human pluripotent cells focus on recapitulating
      the developmental steps required during embryogenesis. In the case of the kidney,
      this has involved mesodermal differentiation through posterior primitive streak
      and intermediate mesoderm. Recent studies have observed the simultaneous
      formation of both ureteric epithelium and nephron progenitors in vitro. These
      component cell types signal to each other to initiate nephron formation as would
      occur during development. SUMMARY: The generation of kidney organoids is a major
      advance in nephrology. Such organoids may be useful for disease modelling and
      drug screening. Ultimately, our capacity to generate organoids may extend to the
      development of tissues for transplantation.

PMID- 25856181
TI  - Adherence with immunosuppression in heart transplant recipients.
AB  - PURPOSE OF REVIEW: Nonadherence is a major problem in heart transplantation (htx)
      and a challenge for clinical practice and research. In heart transplant
      recipients, nonadherence could cause chronic rejection of the transplanted heart
      followed by difficult clinical course and/or death of the patient. RECENT
      FINDINGS: Main topics are the relationship between psychological aspects and
      adherence, risk factors and prediction of nonadherence, strategies for improving
      adherence like single-dose immunosuppressant therapy and follow-up studies.
      SUMMARY: There is a lack of behavioral intervention studies. So-called targeted
      interventions should be defined for clinical practice and research with
      randomized controlled studies.

PMID- 25856182
TI  - Body image in transplant recipients and living organ donors.
AB  - PURPOSE OF REVIEW: The purpose of this article is to describe the current
      evidence regarding the prevalence and significance of concerns about body image
      in transplant recipients and organ donors. RECENT FINDINGS: Body image and organ
      integration concerns have been reported as main themes in the psychological
      adaptation to transplantation. Their prevalence, severity, description and impact
      vary wildly. There is a lack of validated instruments to measure body image or
      organ integration in transplant patients. For organ recipients, satisfaction with
      body image depends on the organ, genre, pretransplant medical illness, time since
      transplantation and post-transplant medication regimen. Complete or partial
      denial of the graft is frequently reported. For organ donors, body image is
      influenced by the type of surgical incision. There is little evidence that body
      image or organ integration impact medical or psychological outcomes after
      transplantation or organ donation. SUMMARY: Body image is becoming a significant
      component of measuring the quality of life in transplant patients. Body image may
      become a factor in decisions about if and when to pursue transplant for nonlife
      threatening conditions (e.g. face transplantation), about the type of incision or
      about the immunosuppressant regimen. For mental health professionals,
      understanding the complexities of body image and organ integration will help
      enhance the assistance provided before and after transplant or donation.

PMID- 25856183
TI  - Pancreas and islet transplantation: psychological themes pre- and posttransplant.
AB  - PURPOSE OF REVIEW: To date, islet and whole pancreas transplantation have been
      largely researched and reported separately. Therefore, for the first time, this
      review seeks to examine together the recently reported psychological issues as
      they relate to the two different types of transplantation. RECENT FINDINGS: In
      relation to pancreas transplantation, recent findings indicate potential issues
      relating to energy levels, including sleep problems; mood problems (anxiety,
      depression, traumatic stress); social interactions; and identity issues.
      Similarly, the research on islet allotransplantation (ITA) indicates mood
      disruptions associated with Type I diabetes mellitus (T1DM), which seem to
      improve as a result of treatment with ITA. SUMMARY: The review indicates a need
      for more research to guide effective intervention to optimize psychological
      recovery post islet and/or pancreas transplantation for patients with T1DM.
      Effective psychological intervention for this group relies on researchers
      eliciting more detailed knowledge of pretransplant psychosocial issues, not only
      in relation to how these might vary by transplant group, but also in relation to
      patient health status vis-a-vis microvascular complications and glycaemic
      control, and how these issues change across the whole transplant journey.

PMID- 25856184
TI  - Liver transplant and quality of life in the pediatric population: a review update
      (2013-2014).
AB  - PURPOSE OF REVIEW: Liver transplantation is emerging as the treatment of choice
      for children with end-stage liver disease and some cases of acute liver failure.
      Owing to improvements in the surgical and medical management of liver
      transplantation, most patients survive surgery and do well physically in the
      posttransplant period. However, quality of life (QOL) for these children remains
      below expectation and is associated with poor psychological and social
      functioning. In this article, we review the recent literature and provide an
      opinion regarding QOL in pediatric liver transplant (PLT) patients and possible
      interventions to optimize it. RECENT FINDINGS: We reviewed articles published in
      2013 and 2014 reporting QOL in PLT survivors. Our review of the literature
      suggests that children undergoing liver transplantation have varying degrees of
      QOL in the post transplantation period despite improvements in medical and
      surgical managements. SUMMARY: It is important to proactively identify and
      address psychological difficulties in patients and their families prior to
      transplant. Following transplantation, a multidisciplinary approach to targeting
      rehabilitation and decreasing negative effects of the transplant may assist with
      improving the QOL for patients and their families.

PMID- 25856185
TI  - Chronic kidney disease in disadvantaged populations.

PMID- 25856192
TI  - Stable radical content and anti-radical activity of roasted Arabica coffee: from
      in-tact bean to coffee brew.
AB  - The roasting of coffee beans generates stable radicals within melanoidins
      produced by non-enzymatic browning. Roasting coffee beans has further been
      suggested to increase the antioxidant (AO) capacity of coffee brews. Herein, we
      have characterized the radical content and AO capacity of brews prepared from
      Coffea arabica beans sourced directly from an industrial roasting plant. In-tact
      beans exhibited electron paramagnetic resonance signals arising from Fe3+, Mn2+
      and at least three distinct stable radicals as a function of roasting time, whose
      intensity changed upon grinding and ageing. In coffee brews, the roasting-induced
      radicals were harboured within the high molecular weight (> 3 kD) melanoidin
      containing fraction at a concentration of 15 nM and was associated with aromatic
      groups within the melanoidins. The low molecular weight (< 3 kD) fraction
      exhibited the highest AO capacity using DPPH as an oxidant. The AO activity was
      not mediated by the stable radicals or by metal complexes within the brew. While
      other non-AO functions of the roasting-induced radical and metal complexes may be
      possible in vivo, we confirm that the in vitro antiradical activity of brewed
      coffee is dominated by low molecular weight phenolic compounds. 

PMID- 25856193
TI  - Intraspecific genetic admixture and the morphological diversification of an
      estuarine fish population complex.
AB  - The North-east American Rainbow smelt (Osmerus mordax) is composed of two glacial
      races first identified through the spatial distribution of two distinct mtDNA
      lineages. Contemporary breeding populations of smelt in the St. Lawrence estuary
      comprise contrasting mixtures of both lineages, suggesting that the two races
      came into secondary contact in this estuary. The overall objective of this study
      was to assess the role of intraspecific genetic admixture in the morphological
      diversification of the estuarine rainbow smelt population complex. The morphology
      of mixed-ancestry populations varied as a function of the relative contribution
      of the two races to estuarine populations, supporting the hypothesis of genetic
      admixture. Populations comprising both ancestral mtDNA races did not exhibit
      intermediate morphologies relative to pure populations but rather exhibited many
      traits that exceeded the parental trait values, consistent with the hypothesis of
      transgressive segregation. Evidence for genetic admixture at the level of the
      nuclear gene pool, however, provided only partial support for this hypothesis.
      Variation at nuclear AFLP markers revealed clear evidence of the two
      corresponding mtDNA glacial races. The admixture of the two races at the nuclear
      level is only pronounced in mixed-ancestry populations dominated by one of the
      mtDNA lineages, the same populations showing the greatest degree of morphological
      diversification and population structure. In contrast, mixed-ancestry populations
      dominated by the alternate mtDNA lineage showed little evidence of introgression
      of the nuclear genome, little morphological diversification and little
      contemporary population genetic structure. These results only partially support
      the hypothesis of transgressive segregation and may be the result of the
      differential effects of natural selection acting on admixed genomes from
      different sources. 

PMID- 25856194
TI  - Research design and statistical methods in Indian medical journals: a
      retrospective survey.
AB  - Good quality medical research generally requires not only an expertise in the
      chosen medical field of interest but also a sound knowledge of statistical
      methodology. The number of medical research articles which have been published in
      Indian medical journals has increased quite substantially in the past decade. The
      aim of this study was to collate all evidence on study design quality and
      statistical analyses used in selected leading Indian medical journals. Ten (10)
      leading Indian medical journals were selected based on impact factors and all
      original research articles published in 2003 (N = 588) and 2013 (N = 774) were
      categorized and reviewed. A validated checklist on study design, statistical
      analyses, results presentation, and interpretation was used for review and
      evaluation of the articles. Main outcomes considered in the present study were -
      study design types and their frequencies, error/defects proportion in study
      design, statistical analyses, and implementation of CONSORT checklist in RCT
      (randomized clinical trials). From 2003 to 2013: The proportion of erroneous
      statistical analyses did not decrease (chi2=0.592, Phi=0.027, p=0.4418), 25%
      (80/320) in 2003 compared to 22.6% (111/490) in 2013. Compared with 2003,
      significant improvement was seen in 2013; the proportion of papers using
      statistical tests increased significantly (chi2=26.96, Phi=0.16, p<0.0001) from
      42.5% (250/588) to 56.7 % (439/774). The overall proportion of errors in study
      design decreased significantly (chi2=16.783, Phi=0.12 p<0.0001), 41.3% (243/588)
      compared to 30.6% (237/774). In 2013, randomized clinical trials designs has
      remained very low (7.3%, 43/588) with majority showing some errors (41 papers,
      95.3%). Majority of the published studies were retrospective in nature both in
      2003 [79.1% (465/588)] and in 2013 [78.2% (605/774)]. Major decreases in error
      proportions were observed in both results presentation (chi2=24.477, Phi=0.17,
      p<0.0001), 82.2% (263/320) compared to 66.3% (325/490) and interpretation
      (chi2=25.616, Phi=0.173, p<0.0001), 32.5% (104/320) compared to 17.1% (84/490),
      though some serious ones were still present. Indian medical research seems to
      have made no major progress regarding using correct statistical analyses, but
      error/defects in study designs have decreased significantly. Randomized clinical
      trials are quite rarely published and have high proportion of methodological
      problems. 

PMID- 25856196
TI  - Correction: Deconstructing the DGAT1 enzyme: membrane interactions at substrate
      binding sites.

PMID- 25856195
TI  - Comparative genome analyses of Serratia marcescens FS14 reveals its high
      antagonistic potential.
AB  - S. marcescens FS14 was isolated from an Atractylodes macrocephala Koidz plant
      that was infected by Fusarium oxysporum and showed symptoms of root rot. With the
      completion of the genome sequence of FS14, the first comprehensive comparative
      genomic analysis of the Serratia genus was performed. Pan-genome and COG analyses
      showed that the majority of the conserved core genes are involved in basic
      cellular functions, while genomic factors such as prophages contribute
      considerably to genome diversity. Additionally, a Type I restriction-modification
      system, a Type III secretion system and tellurium resistance genes are found in
      only some Serratia species. Comparative analysis further identified that S.
      marcescens FS14 possesses multiple mechanisms for antagonism against other
      microorganisms, including the production of prodigiosin, bacteriocins, and multi
      antibiotic resistant determinants as well as chitinases. The presence of two
      evolutionarily distinct Type VI secretion systems (T6SSs) in FS14 may provide
      further competitive advantages for FS14 against other microbes. To our knowledge,
      this is the first report of comparative analysis on T6SSs in the genus, which
      identifies four types of T6SSs in Serratia spp.. Competition bioassays of FS14
      against the vital plant pathogenic bacterium Ralstonia solanacearum and fungi
      Fusarium oxysporum and Sclerotinia sclerotiorum were performed to support our
      genomic analyses, in which FS14 demonstrated high antagonistic activities against
      both bacterial and fungal phytopathogens. 

PMID- 25856197
TI  - Efficacy of intralesional recombinant human epidermal growth factor in chronic
      diabetic foot ulcers.
AB  - OBJECTIVE: The aim of this study was to explore the clinical effects of
      intralesional administration of an epidermal growth factor (EGF) up to complete
      wound closure. METHODS: Seventeen diabetic patients with full-thickness lower
      extremity ulcers of more than 4 weeks of evolution were enrolled in the study.
      Mean ulcer size was 15.5 +/- 7.5 cm(2). Intralesional injections of 75 ug of
      Heberprot-P three times per week for 5-8 weeks were given up to complete wound
      healing. RESULTS: Full granulation response was achieved in all patients in 32.4
      +/- 6.6 days. Complete wound closure was obtained in 16 (94.1%) cases in 53.1 +/-
      4.7 days. The most frequent adverse events were burning sensation, tremors,
      chills and pain at the site of administration. After 1-year follow-up, only one
      patient relapsed. CONCLUSIONS: Intralesional EGF administration up to complete
      closure can be safe, effective and suitable to improve healing of chronic
      diabetic foot ulcer (DFU).

PMID- 25856198
TI  - Rapid high resolution genotyping of Francisella tularensis by whole genome
      sequence comparison of annotated genes ("MLST+").
AB  - The zoonotic disease tularemia is caused by the bacterium Francisella tularensis.
      This pathogen is considered as a category A select agent with potential to be
      misused in bioterrorism. Molecular typing based on DNA-sequence like canSNP
      typing or MLVA has become the accepted standard for this organism. Due to the
      organism's highly clonal nature, the current typing methods have reached their
      limit of discrimination for classifying closely related subpopulations within the
      subspecies F. tularensis ssp. holarctica. We introduce a new gene-by-gene
      approach, MLST+, based on whole genome data of 15 sequenced F. tularensis ssp.
      holarctica strains and apply this approach to investigate an epidemic of lethal
      tularemia among non-human primates in two animal facilities in Germany. Due to
      the high resolution of MLST+ we are able to demonstrate that three independent
      clones of this highly infectious pathogen were responsible for these spatially
      and temporally restricted outbreaks. 

PMID- 25856199
TI  - Limitations and pitfalls in measurements of right ventricular stroke volume in an
      animal model of right heart failure.
AB  - Right heart failure occurs in various heart and pulmonary vascular diseases and
      may be fatal. We aimed to identify limitations in non-invasive measurements of
      right ventricular stroke volume in an animal model of right ventricular failure.
      Data from previous studies randomising rats to pulmonary trunk banding (PTB, n =
      33) causing pressure-overload right ventricular failure or sham operation (n =
      16) was evaluated retrospectively. We measured right ventricular stroke volume by
      high frequency echocardiography and magnetic resonance imaging (MRI). We found
      correlation between right ventricular stroke volume measured by echocardiography
      and MRI in the sham animals (r = 0.677, p = 0.004) but not in the PTB group.
      Echocardiography overestimated the stroke volume compared to MRI in both groups.
      Intra- and inter-observer variation did not explain the difference. Technical,
      physiological and anatomical issues in the pulmonary artery might explain why
      echocardiography over-estimates stroke volume. Flow acceleration close to the
      pulmonary artery banding can cause uncertainties in the PTB model and might
      explain the lack of correlation. In conclusion, we found a correlation in right
      ventricular stroke volume measured by echocardiography versus MRI in the sham
      group but not the PTB group. Echocardiography overestimated right ventricular
      stroke volume compared to MRI. 

PMID- 25856200
TI  - Correction: Associations between work environment and psychological distress
      after a workplace terror attack: the importance of role expectations,
      predictability and leader support.

PMID- 25856201
TI  - Design of Coltuximab Ravtansine, a CD19-Targeting Antibody-Drug Conjugate (ADC)
      for the Treatment of B-Cell Malignancies: Structure-Activity Relationships and
      Preclinical Evaluation.
AB  - Coltuximab ravtansine (SAR3419) is an antibody-drug conjugate (ADC) targeting
      CD19 created by conjugating a derivative of the potent microtubule-acting
      cytotoxic agent, maytansine, to a version of the anti-CD19 antibody, anti-B4,
      that was humanized as an IgG1 by variable domain resurfacing. Four different
      linker-maytansinoid constructs were synthesized (average ~3.5
      maytansinoids/antibody for each) to evaluate the impact of linker-payload design
      on the activity of the maytansinoid-ADCs targeting CD19. The ADC composed of DM4
      (N(2')-deacetyl-N(2')-[4-mercapto-4-methyl-1-oxopentyl]maytansine) conjugated to
      antibody via the N-succinimidyl-4-(2-pyridyldithio)butyrate (SPDB) linker was
      selected for development as SAR3419. A molar ratio for DM4/antibody of between 3
      and 5 was selected for the final design of SAR3419. Evaluation of SAR3419 in
      Ramos tumor xenograft models showed that the minimal effective single dose was
      about 50 MUg/kg conjugated DM4 (~2.5 mg/kg conjugated antibody), while twice this
      dose gave complete regressions in 100% of the mice. SAR3419 arrests cells in the
      G2/M phase of the cell cycle, ultimately leading to apoptosis after about 24 h.
      The results of in vitro and in vivo studies with SAR3419 made with DM4 that was
      [(3)H]-labeled at the C20 methoxy group of the maytansinoid suggest a mechanism
      of internalization and intracellular trafficking of SAR3419, ultimately to
      lysosomes, in which the antibody is fully degraded, releasing lysine-N(epsilon)
      SPDB-DM4 as the initial metabolite. Subsequent intracellular reduction of the
      disulfide bond between linker and DM4 generates the free thiol species, which is
      then converted to S-methyl DM4 by cellular methyl transferase activity. We
      provide evidence to suggest that generation of S-methyl DM4 in tumor cells may
      contribute to in vivo tumor eradication via bystander killing of neighboring
      tumor cells. Furthermore, we show that S-methyl DM4 is converted to the sulfoxide
      and sulfone derivatives in the liver, suggesting that hepatic catabolism of the
      payload to less cytotoxic maytansinoid species contributes to the overall
      therapeutic window of SAR3419. This compound is currently in phase II clinical
      evaluation for the treatment of diffuse large B cell lymphoma. 

PMID- 25856202
TI  - What is it like to walk with the help of a robot? Children's perspectives on
      robotic gait training technology.
AB  - PURPOSE: Robotic gait training is an emerging intervention that holds great
      therapeutic promise in the rehabilitation of children with neuromotor disorders
      such as cerebral palsy (CP). Little is known about children and parents' views on
      this new technology. The purpose of this qualitative study was to investigate the
      expectations and experiences of children with CP in relation to robotic gait
      training using the Lokomat(r)Pro. METHOD: An interpretivist qualitative design
      was employed in which perspectives of children and parents were elicited through
      separate semi-structured interviews to examine expectations of and experiences
      with the Lokomat. RESULTS: Four themes related to children's expectations and
      experiences using the Lokomat were identified: (1) Not sure what to expect, but
      okay, I will do it; (2) It's more than just the Lokomat, it's the people that
      make the difference; (3) Having mixed impressions about the Lokomat; and (4) It's
      probably helping me, but I don't really know. CONCLUSIONS: Rehabilitation
      professionals, researchers and parents are encouraged to reflect on why and how
      one might engage children in gait-related rehabilitation in ways that appeal to
      children's desires and expectations. This may shape how interventions are
      presented to children and how goals and outcomes are framed. Implications for
      Rehabilitation Children in this study did not consistently feel excited about,
      have a wish to use, or have a sustained interest in the use of a robotic
      technology, and at times experienced some anxiety in relation to their
      participation in the intervention. Contrary to assumptions that disabled children
      value walking "normally", children in this study did not express a desire to walk
      in typical (non-disabled) gait patterns, and equated so-called "normal" walking
      with their usual walking styles. Thus, we encourage clinicians, researchers and
      parents to reflect on why, when and how best to engage children in gait-related
      rehabilitation in ways that appeal to and align with children's desires and
      expectations.

PMID- 25856203
TI  - Factors associated with community ambulation in chronic stroke.
AB  - PURPOSE: Loss of independent community ambulation is one of the most disabling
      consequences of stroke. The aim of this study was to investigate the association
      of multiple personal and post-stroke factors with community ambulation in persons
      between 1- and 3-year post-stroke. METHODS: This was a cross-sectional study of
      40 community-dwelling stroke patients, >18 years, between 1- and 3-year post
      stroke. The main outcome measures used were self-report community ambulation
      questionnaire, demographic information, 10-M Walk Test, Timed Up and Go test,
      Activities-Specific Balance Confidence Scale, Fatigue Severity Scale, Hospital
      Anxiety and Depression Scale, Trail-Making Test-Part B, Single Letter
      Cancellation Test. RESULTS: Age, number of medications and use of a walking aid
      were found to be significantly associated with community ambulation (p <= 0.05).
      Gait speed, walking balance and balance self-efficacy were also found to be
      significantly associated with community ambulation (p <= 0.05). Balance self
      efficacy was the only factor independently associated with community ambulation
      post-stroke (p <= 0.05). CONCLUSION: Balance self-efficacy may be a significant
      determinant in the attainment of independent community ambulation post-stroke.
      This suggests that physical aspects such as gait speed and walking balance should
      not be considered in isolation when addressing community ambulation post-stroke.
      IMPLICATIONS FOR REHABILITATION: Balance self-efficacy may play a significant
      role in the attainment of independent community ambulation in a chronic stroke
      population. Physiotherapy interventions addressing community ambulation post
      stroke should consider methods for improving balance self-efficacy in chronic
      stroke, such as self management programmes.

PMID- 25856205
TI  - Efficient oxygen reduction catalysts formed of cobalt phosphide nanoparticle
      decorated heteroatom-doped mesoporous carbon nanotubes.
AB  - Oxygen reduction catalysts based on heteroatom-doped mesoporous carbon nanotubes
      loaded with Co2P nanoparticles were skilfully fabricated. The electronic
      interaction between the embedded Co2P nanoparticles and the heteroatom-doped
      carbon structures could strongly promote the ORR catalytic performance of the
      heteroatom-doped carbon nanotubes. 

PMID- 25856204
TI  - Experimental Assessment of the Efficacy of Five Veterinary Broad-Spectrum
      Anthelmintics to Control the Intestinal Capillariasis in Zebrafish (Danio rerio).
AB  - Zebrafish in research facilities are frequently infected with capillarids. Since
      the health status (as a nonprotocol source of variation) of zebrafish can affect
      the validity of experiments, it is important to develop therapies for common
      zebrafish diseases. Regarding the likelihood of (1) the development of drug
      resistance and (2) the loss of the efficacy of a drug for laboratory zebrafish,
      the availability of alternatives for treatment is of direct importance. The
      efficacy of five dewormers from the same or different therapeutic groups was
      assessed in the current study. The exposure to each drug was repeated in
      triplicate (i.e., 3*100 fish in each treatment). The (1) elimination of parasite
      eggs, larvae, or adults from fresh fecal droppings (as the first main criterion)
      and (2) dissection of one-third of treated fish (i.e., 100 fish per drug) and
      examination of their gut contents (as the second major criterion) were considered
      to verify the efficacy of the drugs to eradicate the infection. Mebendazole
      (meb), praziquantel (pra; after the first round of treatment, i.e., six-fold
      administration, twice a day, for 3 days), fenbendazole (fen; after the second
      round of treatment), and ivermectin (ive; just after two administrations: twice
      during a day, i.e., a successful treatment with the smallest therapeutic effort)
      eradicated the infection, while albendazol (alb) was ineffective, although alb in
      a combined therapy with fen was successful. No age-, sex-, or disease severity
      dependent responses to drugs were observed. The meb, pra, and ive were
      eliminating parasite eggs effectively in contrast with fen (that just was
      effective on adults). The drugs produced no observable side effects in zebrafish.

PMID- 25856206
TI  - Unlike ASXL1 and ASXL2 mutations, ASXL3 mutations are rare events in acute
      myeloid leukemia with t(8;21).

PMID- 25856207
TI  - Genetics of the serrated pathway to colorectal cancer.

PMID- 25856208
TI  - Electrochemical analyses of redox-active iron minerals: a review of nonmediated
      and mediated approaches.
AB  - Redox-active minerals are ubiquitous in the environment and are involved in
      numerous electron transfer reactions that significantly affect biogeochemical
      processes and cycles as well as pollutant dynamics. As a consequence, research in
      different scientific disciplines is devoted to elucidating the redox properties
      and reactivities of minerals. This review focuses on the characterization of
      mineral redox properties using electrochemical approaches from an applied
      (bio)geochemical and environmental analytical chemistry perspective. Establishing
      redox equilibria between the minerals and working electrodes is a major challenge
      in electrochemical measurements, which we discuss in an overview of traditional
      electrochemical techniques. These issues can be overcome with mediated
      electrochemical analyses in which dissolved redox mediators are used to increase
      the rate of electron transfer and to facilitate redox equilibration between
      working electrodes and minerals in both amperometric and potentiometric
      measurements. Using experimental data on an iron-bearing clay mineral, we
      illustrate how mediated electrochemical analyses can be employed to derive
      important thermodynamic and kinetic data on electron transfer to and from
      structural iron. We summarize anticipated methodological advancements that will
      further contribute to advance an improved understanding of electron transfer to
      and from minerals in environmentally relevant redox processes. 

PMID- 25856209
TI  - Influence of blinded wound closure on the volume stability of different GBR
      materials: an in vitro cone-beam computed tomographic examination.
AB  - OBJECTIVE: To test whether the use of (i) particulated bone substitute + collagen
      membrane used for guided bone regeneration (GBR) of peri-implant bone defects
      renders different results from (ii) particulated bone substitute + collagen
      membrane + fixation pins and from (iii) block bone substitute + collagen membrane
      with respect to the volume stability of the augmented region during suturing of
      mucosal flaps. MATERIAL AND METHODS: Twenty peri-implant box-shaped bone defects
      were created in 10 pig mandibles. Every bone defect was augmented once with each
      of the following GBR procedures: Granulate (particulated xenograft + collagen
      membrane), Granulate + Pins (particulated xenograft + collagen membrane +
      fixation pins), and Block (block xenograft + collagen membrane). Cone-beam
      computed tomography scans were obtained prior and after blinded wound closure.
      The horizontal thickness (HT) of the augmented region (bone substitute +
      membrane) was assessed at the implant shoulder (HT0 mm ) and at 1-5 mm apical to
      the implant shoulder (HT1 mm -HT5 mm ). The changes of HT during flap suturing
      were calculated as absolute (mm) and relative values (%). Repeated-measures ANOVA
      was used for statistical analysis. RESULTS: Wound closure induced a statistically
      significant change of HT0 mm and of HT1 mm in all the treatment groups (P <=
      0.05). The change in HT0 mm measured -42.8 +/- 17.9% (SD) for Granulate, -22.9 +/
      21.2% (SD) for Granulate + Pins, and -20.2 +/- 18.9% (SD) for Block. The
      reduction in HT0 mm, HT1 mm , HT2 mm, and HT3 mm for the Granulate procedure was
      significantly higher as compared to the Granulate + Pins and the Block procedures
      (P <= 0.05). There were no statistically significant differences in the change of
      HT between the Granulate + Pins and the Block procedures (P > 0.05). CONCLUSION:
      Wound closure induced displacement of the bone substitute resulting in a partial
      collapse of the collagen membrane in the coronal portion of the augmented site.
      The stability of the bone substitute and collagen membrane was enhanced by the
      application of fixation pins and by the use of block bone substitute instead of
      particulated bone substitute.

PMID- 25856210
TI  - Relationship of Bone Metabolism Biomarkers and Periodontal Disease: The
      Osteoporotic Fractures in Men (MrOS) Study.
AB  - CONTEXT: Periodontitis is an inflammatory disease of tooth-supporting tissue
      leading to bone destruction and tooth loss. Periodontitis affects almost 50% of
      adults greater than 30 years of age. OBJECTIVE: This study evaluated the
      association between biomarkers linked to bone formation and resorption with the
      occurrence and progression of periodontal disease in older men (>= 65 y). DESIGN:
      The Osteoporotic Fractures in Men (MrOS) study is a prospective, observational
      study among men 65 years of age and older. SETTING: This ancillary study, Oral
      and Skeletal Bone Loss in Older Men, was conducted at two of the six MrOS study
      sites (Birmingham, AL and Portland, OR). PATIENTS: Patients underwent medical and
      dental evaluation. Diagnoses of periodontitis were based on clinical attachment
      loss, pocket depth, calculus, plaque, and bleeding on a random half-mouth. Bone
      metabolism biomarkers included serum levels of calcium, phosphate (Pi), alkaline
      phosphatase, albumin, carboxy-terminal collagen crosslinks (CTX), N-terminal
      propeptides of type I procollagen, isoform 5b of tartrate-resistant acid
      phosphatase, and urine alpha- carboxy-terminal collagen crosslinks (alpha-CTX)
      and beta-CTX and serum levels of calciotropic hormones vitamin D (25(OH)D) and
      PTH. MAIN OUTCOME MEASURES: The aim of this study is to correlate bone metabolism
      biomarkers with prevalence and progression of periodontal disease in older men.
      RESULTS: Patients with more severe periodontitis had significantly higher levels
      of PTH (P trend = .0004), whereas 25(OH)D was lower (P trend = .001). In a subset
      of men reevaluated at a second dental visit, improvement of periodontitis was
      associated with lower alpha-CTX, beta-CTX, and CTX levels at baseline after
      adjusting for age, site, and body mass index. CONCLUSION: This study suggests
      that a distinct set of biomarkers of bone metabolism are associated with more
      severe periodontal disease (PTH, 25(OH)D) and periodontal progression (alpha-CTX,
      beta-CTX, and CTX) over time.

PMID- 25856212
TI  - Thresholds for Serum 25(OH)D Concentrations With Respect to Different Outcomes.
AB  - CONTEXT: Vitamin D is essential for bone health. In addition, vitamin D has
      recently been proposed to play a role in the pathophysiology of many chronic
      diseases. Despite the large number of studies published on vitamin D, the
      threshold for a sufficient serum 25-hydroxyvitamin D [25(OH)D] concentration is
      still debated and may differ according to outcomes and subgroups. OBJECTIVE: The
      objective of the study was to estimate the thresholds for serum 25(OH)D
      concentration with respect to the different outcomes and for different subgroups.
      DESIGN, SETTING, AND PARTICIPANTS: Observational data from the Longitudinal Aging
      Study Amsterdam, an ongoing population-based Dutch cohort study [n = 1164, mean
      (SD) age 75.2 (6.5) y], were used. MAIN OUTCOME MEASURES: Falling, fractures,
      hypertension, cardiovascular disease, blood pressure, PTH, grip strength,
      physical performance, functional limitations, body mass index (BMI), and
      mortality were measured. To determine thresholds, spline curves were used. Visual
      inspection and the statistical best fit of the spline regression models were used
      together to estimate the best estimate of the thresholds. RESULTS: Thresholds for
      serum 25(OH)D concentrations in the whole sample ranged from 46 nmol/L (PTH) to
      68 nmol/L (hypertension). On average, women, the oldest old (>= 75 y), and
      individuals with a high BMI (>25 kg/m(2)) had lower thresholds compared with men,
      the youngest old (65-75 y), and individuals with a low to normal BMI (<25
      kg/m(2)). CONCLUSION: The results indicate that thresholds for serum 25(OH)D may
      vary according to different outcomes and subgroups. This study does not support
      the high thresholds (>75 nmol/L) as advised by some experts, and the higher
      requirements in women, older persons, and those with high BMI.

PMID- 25856211
TI  - Impact of Male and Female Weight, Smoking, and Intercourse Frequency on Live
      Birth in Women With Polycystic Ovary Syndrome.
AB  - CONTEXT: Obese men with normal semen parameters exhibit reduced fertility but few
      prospective data are available. OBJECTIVE: This study aimed to determine the
      effect of male factors and body mass among the Pregnancy in Polycystic Ovary
      Syndrome II (PPCOS II) participants. METHODS: This is a secondary analysis of the
      PPCOS II trial. A total of 750 infertile women with polycystic ovary syndrome
      (PCOS) were randomly assigned to up to receive five cycles of letrozole or
      clomiphene citrate. Females were 18-39-years-old and had a male partner with
      sperm concentration of at least 14 million/mL who consented to regular
      intercourse. Analysis was limited to couples with complete male partner
      information (n = 710). RESULTS: Male body mass index (BMI) was higher in couples
      who failed to conceive (29.5 kg/m(2) vs 28.2 kg/m(2); P = .039) as well as those
      who did not achieve a live birth (29.5 kg/m(2) vs 28.1 kg/m(2); P = .047). At
      least one partner was obese in 548 couples (77.1%). A total of 261 couples were
      concordant for obesity (36.8%). After adjustment for female BMI, the association
      of male BMI with live birth was no longer significant (odds ratio [OR] = 0.85; 95
      % confidence interval [CI], 0.68-1.05; P = .13). Couples in which both partners
      smoked had a lower chance of live birth vs nonsmokers (OR = 0.20; 95 % CI, 0.08
      0.52; P = .02), whereas there was not a significant effect of female or male
      smoking alone. Live birth was more likely in couples with at least three sexual
      intercourse attempts over the previous 4 weeks (reported at baseline) as opposed
      to couples with lesser frequency (OR = 4.39; 95 % CI, 1.52-12. 4; P < .01).
      CONCLUSIONS: In this large cohort of obese women with PCOS, effect of male
      obesity was explained by female BMI. Lower chance of success was seen among
      couples where both partners smoked. Obesity and smoking are common among women
      with PCOS and their partners and contribute to a decrease in fertility treatment
      success.

PMID- 25856214
TI  - Estrogens and Their Genotoxic Metabolites Are Increased in Obese Prepubertal
      Girls.
AB  - CONTEXT: Estrogen levels and their metabolites are higher in obese vs lean
      postmenopausal women, and obesity increases breast cancer risk. Quinone
      derivatives of 4-hydroxylated estrogen metabolites, independently of the estrogen
      receptor, cause depurination and impaired DNA repair (genotoxic). 16alpha-Hydroxy
      (16alpha-OH)-estrone (E1), eg, promotes tumor proliferation and 2-methoxy
      estradiol (E2) may be chemoprotective. Childhood obesity increases breast cancer
      death risk in women, but levels of estrogen derivatives had not been previously
      studied in young children. OBJECTIVE: The objective of the study was to
      investigate whether total and genotoxic estrogens are increased in prepubertal
      obese girls compared with lean controls. DESIGN: Stored sera from 12 lean and 23
      obese prepubertal girls (Tanner stage I breast and pubic hair) studied previously
      were assayed for E1, E2, and their multiple metabolites (12 steroids total) using
      highly sensitive liquid chromatography and tandem mass spectrometry. RESULTS: E2
      concentrations were significantly higher in obese [3.45 (0.5, 4.65) pg/ml (median
      [quartile 1, quartile 3])] vs lean girls [0.5 (0.5, 2.37), P = .04], 57% of
      values upper quartile or greater (quartile 3) of controls. Concentrations of
      16alpha-OH-E1 were higher in obese [7.17 (0.5, 9.64) pg/mL] vs lean girls [0.5
      (0.5, 1.72, P = .007)], 65% of values quartile 3 or greater of controls. 2
      Methoxy-E2 concentrations were lower in the obese group (P = .012). 16alpha-OH-E1
      concentrations were positively correlated with body mass index, percentage fat
      mass, and IL-6 concentrations (P < .001). CONCLUSIONS: E2 and genotoxic
      metabolites were higher in obese vs lean prepubertal girls. These data suggest
      that obesity is associated with an increased extraglandular estrogen production
      and metabolism before the onset of puberty in girls. Long-term epidemiological
      studies are needed to assess any potential increase in breast cancer risk.

PMID- 25856216
TI  - Sacral decubitus after cervical spine injury: a case report and suggestions for
      avoiding such wounds.
AB  - Sacral decubitus ulcers after cervical spine injuries are particularly
      debilitating wounds. An illustrative case is presented here and strategies are
      proposed that may help reduce the incidence of this type of wound. These include
      early involvement in the patient's care by a wound prevention specialist and the
      incorporation of a cholera cot design into the spinal transport board with a hole
      to completely offload the sacral tissue and permit the drainage of stool. Because
      intermittent visual inspection of skin is probably inadequate to detect the first
      sign of impending complications, there is a need for technology to objectively
      assess the status of skin's integrity so a computer program could automatically
      adjust the pressure on the patient's skin and alert the doctor. Sophisticated
      equipment that measures mattress pressure on skin is now widely available;
      sensors of this type could be situated on top of a quilt of miniature air bags
      (ie, smart cubes) so that individual computer-controlled areas of the quilt could
      be deflated to offload pressure as required. In the future, probes capable of
      measuring CO2 production, electrical resistance, or even polarization
      spectroscopy might be interspersed among the cubes so that ongoing skin viability
      and integrity could also be monitored. Finally, if the middle model, which
      proposes that pressure damage starts deep in the middle of the tissue overlying
      the sacrum before spreading to the skin, proves to be correct and the ground zero
      for some decubitus really is in the sacral fat, then even more advanced
      monitoring will be required such as implantable biosensors, and treatment plans
      might require hyperbaric oxygen or even preemptive liposuction of necrotic fat. 

PMID- 25856217
TI  - Edaravone, a free radical scavenger, accelerates wound healing in diabetic mice.
AB  - Refractory wound healing is a major complication of diabetes, which restricts
      wound healing by interfering with the inflammatory response, decreasing
      granulation, causing peripheral neuropathy, and inhibiting angiogenesis.
      Oxidative stress has been proposed as an important pathogenic factor in diabetic
      wound complications. Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) is a strong
      free radical scavenger that suppresses the effect of oxidative stress. MATERIAL
      AND METHODS: Streptozotocin-induced diabetes was established in adult C57BL/6
      mice, and full-thickness skin was then removed from the dorsomedial back using an
      8-mm biopsy punch. Edaravone or vehicle alone was applied to the wound on day 0
      and day 4 after wound creation. The wound was monitored with a digital camera and
      analyzed on days 0, 4, and 7 after wound creation. RESULTS: This study
      investigated whether accelerated wound closure occurred in the edaravone group (n
      = 24) compared with the vehicle-alone group (n = 15). On day 7, wound closure
      between the 2 groups was statistically different (P = 0.0019). Angiogenesis and
      lymphangiogenesis were markedly promoted. The possibility of an inhibitory effect
      of edaravone characterized by suppression of oxidative stress was explored.
      Edaravone-induced upregulation of endothelial nitric oxide synthase (eNOS) mRNA
      expression, and eNOS protein was immunohistochemically detected. CONCLUSION:
      Edaravone upregulates eNOS expression and accelerates wound healing.

PMID- 25856215
TI  - Evidence that TSH Receptor A-Subunit Multimers, Not Monomers, Drive Antibody
      Affinity Maturation in Graves' Disease.
AB  - CONTEXT: The TSH receptor (TSHR) A-subunit shed from the cell surface contributes
      to the induction and/or affinity maturation of pathogenic TSHR autoantibodies in
      Graves' disease. OBJECTIVE: This study aimed to determine whether the quaternary
      structure (multimerization) of shed A-subunits influences pathogenic TSHR
      autoantibody generation. DESIGN: The isolated TSHR A-subunit generated by
      transfected mammalian cells exists in two forms; one (active) is recognized only
      by Graves' TSHR autoantibodies, the second (inactive) is recognized only by mouse
      monoclonal antibody (mAb) 3BD10. Recent evidence suggests that both Graves' TSHR
      autoantibodies and mAb 3BD10 recognize the A-subunit monomer. Therefore, if the A
      subunit monomer is an immunogen, Graves' sera should have antibodies to both
      active and inactive A-subunits. Conversely, restriction of TSHR autoantibodies to
      active A-subunits would be evidence of a role for shed A-subunit multimers, not
      monomers, in the pathogenesis of Graves' disease. Therefore, we tested a panel of
      Graves' sera for their relative recognition of active and inactive A-subunits.
      RESULTS: Of 34 sera from unselected Graves' patients, 28 were unequivocally
      positive in a clinical TSH binding inhibition assay. None of the latter sera, as
      well as 8/9 sera from control individuals, recognized inactive A-subunits on
      ELISA. In contrast to Graves' sera, antibodies induced in mice, not by shedding
      from the TSHR holoreceptor, but by immunization with adenovirus expressing the
      free human A-subunit, were directed to both the active and inactive A-subunit
      forms. CONCLUSIONS: The present study supports the concept that pathogenic TSHR
      autoantibody affinity maturation in Graves' disease is driven by A-subunit
      multimers, not monomers.

PMID- 25856213
TI  - Subclinical Hypothyroidism and the Risk of Stroke Events and Fatal Stroke: An
      Individual Participant Data Analysis.
AB  - OBJECTIVE: The objective was to determine the risk of stroke associated with
      subclinical hypothyroidism. DATA SOURCES AND STUDY SELECTION: Published
      prospective cohort studies were identified through a systematic search through
      November 2013 without restrictions in several databases. Unpublished studies were
      identified through the Thyroid Studies Collaboration. We collected individual
      participant data on thyroid function and stroke outcome. Euthyroidism was defined
      as TSH levels of 0.45-4.49 mIU/L, and subclinical hypothyroidism was defined as
      TSH levels of 4.5-19.9 mIU/L with normal T4 levels. DATA EXTRACTION AND
      SYNTHESIS: We collected individual participant data on 47 573 adults (3451
      subclinical hypothyroidism) from 17 cohorts and followed up from 1972-2014 (489
      192 person-years). Age- and sex-adjusted pooled hazard ratios (HRs) for
      participants with subclinical hypothyroidism compared to euthyroidism were 1.05
      (95% confidence interval [CI], 0.91-1.21) for stroke events (combined fatal and
      nonfatal stroke) and 1.07 (95% CI, 0.80-1.42) for fatal stroke. Stratified by
      age, the HR for stroke events was 3.32 (95% CI, 1.25-8.80) for individuals aged
      18-49 years. There was an increased risk of fatal stroke in the age groups 18-49
      and 50-64 years, with a HR of 4.22 (95% CI, 1.08-16.55) and 2.86 (95% CI, 1.31
      6.26), respectively (p trend 0.04). We found no increased risk for those 65-79
      years old (HR, 1.00; 95% CI, 0.86-1.18) or >= 80 years old (HR, 1.31; 95% CI,
      0.79-2.18). There was a pattern of increased risk of fatal stroke with higher TSH
      concentrations. CONCLUSIONS: Although no overall effect of subclinical
      hypothyroidism on stroke could be demonstrated, an increased risk in subjects
      younger than 65 years and those with higher TSH concentrations was observed.

PMID- 25856218
TI  - Feelings of powerlessness in patients with diabetic foot ulcers.
AB  - The purpose of this study was to assess feelings of powerlessness in patients
      with diabetic foot ulcers. Chronic wounds affect the emotional state of patients,
      who may experience negative emotions including a sense of loss and powerlessness.
      The assessment of these feeling should contribute to the planning of
      interventions aimed at minimizing the impact of diabetic foot ulcers on the daily
      lives of these patients. METHODS: Fifty patients >= 18 years of age with type 1
      or type 2 diabetes and foot ulcers were selected from 2 outpatient wound-care
      clinics to participate in the study. Of these patients, 50% were 61-70 years old,
      72% were women, 74% were smokers, 10% were alcoholics, 40% had a diabetic foot
      ulcer for 3-6 years, and 22% for 7-10 years. Wound odor and exudate were present
      in 82% of patients. Individuals who were unable to respond to a questionnaire due
      to physical or cognitive deficit were excluded. All participants responded to the
      Powerlessness Assessment Tool for adult patients (PAT), with scores ranging from
      12-60, with higher scores corresponding to feelings of more intense
      powerlessness. RESULTS: Total PAT scores ranged from 31-40 for 5 (10%) patients,
      51-60 for 28 (56%) patients and from 41-50 for 17 (34%) patients. All patients
      reported total and subscale PAT scores >= 34 (moderate to high scores), with a
      mean total score of 50.12. The maximum PAT score of 60 was reported on the "self
      perception of decision-making capacity" domain. CONCLUSION: These results
      indicate that patients with diabetic foot ulcers had strong feelings of
      powerlessness.

PMID- 25856219
TI  - Leptin, ghrelin, and adiponectin in the metabolic adjustment to burn injury in
      children.
AB  - OBJECTIVE: Leptin, adiponectin, and ghrelin have diverse roles in the control of
      inflammation and metabolism in a normal state as well as in a chronic disease
      state. The aim of this study was to evaluate their role in the extreme metabolic
      and proinflammatory state after burn injury and during the initial weeks of
      recovery. METHODS: A prospective descriptive study in a tertiary care center was
      undertaken. Patients were comprised of 5 children aged 20-108 months with severe
      burn injury; burn size ranged from 15%-36% of total body surface area. Early
      enteral feeding, according to estimated energy expenditure, was initiated as 150%
      of the recommended dietary allowance and in accordance with the patients'
      nitrogen balance. Seven blood samples were collected sequentially, approximately
      5 days apart, during the first 65 days after the burn injury. Samples were tested
      for leptin, ghrelin, and adiponectin. RESULTS: Leptin, ghrelin, and adiponectin
      had a similar trajectory of concentration over time: low levels at the beginning,
      increasing until 2-3 weeks post-burn, where they reached a plateau at 5 weeks
      post-injury. The typical inverse correlations of ghrelin and adiponectin with
      leptin were absent. Interleukin-6 was negatively associated with ghrelin and
      adiponectin and was not associated with leptin. Insulin-like growth factor-1 (IGF
      1) had a positive association with the 3 hormones; however, their profiles differ
      in their relationship to the expected concentration based on a literature review.
      Ghrelin and adiponectin were higher, leptin and IGF-1 were lower than expected.
      CONCLUSIONS: In the early weeks after burn injury, the hypermetabolic state and
      inflammation have a major effect on leptin, ghrelin, and adiponectin. The
      concurrent and similar change of the 3 hormones serves the parallel anabolic and
      catabolic processes during the recovery from burn injury.    .

PMID- 25856220
TI  - Effects of Probiotic Supplementation on Oxidative Stress Indices in Women with
      Rheumatoid Arthritis: A Randomized Double-Blind Clinical Trial.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) is an autoimmune inflammatory disease that
      causes great pain and disability and increasing oxidative stress in patients. The
      objective of the present study was to evaluate the effects of probiotics-live
      microorganisms with many health benefits, including antioxidant properties-on
      oxidative stress indices of patients with RA. This study is a secondary analysis
      from a previously published study Methods: In a randomized double-blind placebo
      controlled clinical trial, 46 patients with RA were assigned to one of two
      groups; patients in the probiotic group received a daily capsule containing 10(8)
      colony forming units (CFUs) of Lactobacillus casei 01 (L. casei 01), while those
      in the placebo group took identical capsules containing maltodextrin, for 8
      weeks. In the baseline and at the end of the study, anxiety, physical activity
      levels, and dietary intakes were assessed. Anthropometric parameters, serum
      malondialdehyde (MDA), total antioxidant capacity (TAC), erythrocyte superoxide
      dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) activities were
      measured. RESULTS: There was no significant difference between the two groups for
      demographic characteristics, anthropometric parameters, physical activity,
      anxiety levels, or dietary intakes, throughout the course of the study. No
      significant within- and between-group differences were observed for MDA, TAC, or
      CAT. SOD activity decreased only in the probiotic group and GPx activity
      decreased in both study groups (p < 0.05); however, no significant between-group
      difference was found for these enzymes activities at the end of the study (p >
      0.05). CONCLUSION: No significant effect of L. casei 01 supplementation was
      observed on the oxidative status of patients with RA, compared to placebo.

PMID- 25856221
TI  - Increased intake of selected vegetables, herbs and fruit may reduce bone turnover
      in post-menopausal women.
AB  - Increased consumption of vegetables/herbs/fruit may reduce bone turnover and
      urinary calcium loss in post-menopausal women because of increased intake of
      polyphenols and potassium, but comparative human studies are lacking. The main
      aim was to compare bone turnover markers and urinary calcium excretion in two
      randomised groups (n = 50) of healthy post-menopausal women consuming >= 9
      servings of different vegetables/herbs/fruit combinations (three months). Group A
      emphasised a generic range of vegetables/herbs/fruit, whereas Group B emphasised
      specific vegetables/herbs/fruit with bone resorption-inhibiting properties
      (Scarborough Fair Diet), with both diets controlled for potential renal acid load
      (PRAL). Group C consumed their usual diet. Plasma bone markers, urinary
      electrolytes (24 h) and estimated dietary PRAL were assessed at baseline and 12
      weeks. Procollagen type I N propeptide (PINP) decreased (-3.2 MUg/L, p < 0.01) in
      the B group only, as did C-terminal telopeptide of type I collagen (CTX) (-0.065
      MUg/L, p < 0.01) in women with osteopenia compared to those with normal bone
      mineral density (BMD) within this group. Intervention Groups A and B had
      decreased PRAL, increased urine pH and significantly decreased urinary calcium
      loss. Urinary potassium increased in all groups, reflecting a dietary change. In
      conclusion, Group B demonstrated positive changes in both turnover markers and
      calcium conservation.

PMID- 25856222
TI  - The key role of government in addressing the pandemic of micronutrient deficiency
      conditions in Southeast Asia.
AB  - Micronutrient deficiency conditions are a major global public health problem.
      While the private sector has an important role in addressing this problem, the
      main responsibility lies with national governments, in cooperation with
      international agencies and donors. Mandatory fortification of basic foods
      provides a basic necessary intake for the majority and needs to be supported by
      provision of essential vitamin and mineral supplements for mothers and children
      and other high risk groups. Fortification by government mandate and regulation is
      essential with cooperation by private sector food manufacturers, and in the
      context of broader policies for poverty reduction, education and agricultural
      reform. Iron, iodine, vitamin A, vitamin B complex, folic acid, zinc, vitamin D
      and vitamin B12 are prime examples of international fortification experience
      achieved by proactive governmental nutrition policies. These are essential to
      achieve the Millennium Development Goals and their follow-up sustainable global
      health targets. National governmental policies for nutritional security and
      initiatives are essential to implement both food fortification and targeted
      supplementation policies to reduce the huge burden of micronutrient deficiency
      conditions in Southeast Asia and other parts of the world. 

PMID- 25856223
TI  - The challenges of home enteral tube feeding: a global perspective.
AB  - The aim of this review is to provide a global perspective of Home Enteral Tube
      Feeding (HETF) and to outline some of the challenges of home enteral nutrition
      (HEN) provisions. It is well established that the number of patients on HETF is
      on the increase worldwide due to advances in technology, development of
      percutaneous endoscopic gastrostomy techniques, and the shift in care provisions
      from acute to community settings. While the significance of home enteral
      nutrition in meeting the nutritional requirements of patients with poor
      swallowing reflexes and those with poor nutritional status is not in doubt,
      differences exist in terms of funding, standards, management approaches and the
      level of infrastructural development across the world. Strategies for alleviating
      some of the challenges militating against the effective delivery of HETF
      including the development of national and international standards, guidelines and
      policies for HETF, increased awareness and funding by government at all levels
      were discussed. Others, including development of HEN services, which should
      create the enabling environment for multidisciplinary team work, clinical audit
      and research, recruitment and retention of specialist staff, and improvement in
      patient outcomes have been outlined. However, more research is required to fully
      establish the cost effectiveness of the HEN service especially in developing
      countries and to compare the organization of HEN service between developing and
      developed countries. 

PMID- 25856224
TI  - Tumor microenvironment in focus: LA-ICP-MS bioimaging of a preclinical tumor
      model upon treatment with platinum(IV)-based anticancer agents.
AB  - The selection of drug candidates for entering clinical development relies on in
      vivo testing in (solid) tumor animal models. However, the heterogeneity of tumor
      tissue (e.g. in terms of drug uptake or tissue composition) is rarely considered
      when testing novel drug candidates. Therefore, we used the murine colon cancer CT
      26 tumor model to study the spatially-resolved drug distribution in tumor tissue
      upon repetitive treatment of animals over two weeks with three investigational
      platinum(IV)-based anticancer agents, oxaliplatin or satraplatin. A quantitative
      laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) imaging
      method revealed a heterogeneous platinum distribution, which correlated well with
      the histologic features of the tumor and surrounding tissue at the microscopic
      level. In most of the cases, higher amounts of intratumoral platinum were found
      in the surrounding tissue than in the malignant parts of the sample. This
      indicates that determination of average platinum amounts (e.g. by microwave
      assisted digestion of the sample followed by analysis with ICP-MS) might
      overestimate the drug uptake in tumor tissue causing misleading conclusions. In
      addition, we studied the platinum distribution in the kidneys of treated animals
      to probe if accumulation in the cortex and medulla predict potential
      nephrotoxicity. A 10-fold increase of platinum in the cortex of the kidney over
      the medulla was observed for oxaliplatin and satraplatin. Although these findings
      are similar to those in the platinum distribution of the nephrotoxic anticancer
      drug cisplatin, treatment with the compounds of our study did not show signs of
      nephrotoxicity in clinical use or clinical trials (oxaliplatin, satraplatin) and
      did not result in the alteration of renal structures. Thus, predicting the side
      effects based on bioimaging data by LA-ICP-MS should be considered with caution.
      To the best of our knowledge, this is the first LA-ICP-MS study on spatially
      resolved platinum accumulation in tissues after repetitive platinum-based
      anticancer drug treatment of mice bearing a preclinical tumor model.

PMID- 25856225
TI  - Monthly ibandronate versus weekly risedronate treatment for low bone mineral
      density in stable renal transplant patients.
AB  - INTRODUCTION: Bisphosphonates may aid in treating and preventing bone loss
      promoted by chronic immunosuppressive treatment and secondary hyperparathyroidism
      in renal transplant (RT) patients. However, the effectiveness of bisphosphonates
      is compromised by poor patient compliance. The objective of the study was to
      compare the effects of once monthly ibandronate with those of weekly risedronate
      administration on bone mineral density (BMD) and renal function in RT patients.
      PATIENTS AND METHODS: Sixty-nine patients were prospectively recruited who were
      at least 12 months post-RT and were treated with either oral ibandronate 150 mg
      monthly (n=35) or oral risedronate 35 mg weekly (n=34). At baseline and 1 year,
      creatinine, calcium, alkaline phosphatase, and i-parathyroid hormone were
      measured, and BMD was determined by dual-energy X-ray absorptiometry. RESULTS:
      Group I consisted of 35 patients (28 women) treated with ibandronate who were of
      a mean age of 63+/-12 years. Group II consisted of 34 patients (30 women) treated
      with risedronate who were of a mean age of 64+/-10 years. Lumbar BMD was as
      follows: baseline T-score (group I vs. group II) of -1.7+/-0.8 versus -1.9+/-0.8
      (P=NS); and annual T-score of -1.3+/-0.6 versus -1.4+/-0.8 (P=NS). After 1 year,
      lumbar BMD improved to reveal a T-score of -1.3+/-0.6 in the ibandronate group
      (P<0.01) and -1.4+/-0.8 in the risedronate group (P<0.01). Femoral BMD was as
      follows: baseline T-score (group I vs. group II) of -2.1+/-0.7 versus -2.2+/-0.6
      (P=NS); and annual T-score of -1.8+/-0.9 versus -1.8+/-0.8 (P=NS). Cortical bone
      also improved in both groups, but results were not statistically significant. No
      changes in renal function and no adverse effects were observed. CONCLUSION: In RT
      patients with low BMD, no difference in effects on BMD, renal function, or
      adverse effects were observed between monthly oral ibandronate and weekly oral
      risedronate administration.

PMID- 25856226
TI  - Sexual health education in U.S. physician assistant programs.
AB  - INTRODUCTION: Since the 1950s, sexual health education in medical schools has
      been evaluated and reported upon, but there has never been an assessment
      published about sexual health curricula in U.S. physician assistant (PA)
      programs. AIM: The aim of this study was to gain better understanding of how PA
      programs cover sexual health topics. METHODS: Between January and March 2014, 181
      accredited PA programs received a mailed survey inquiring about their sexual
      health curriculum. MAIN OUTCOME MEASURES: The survey assessed general sexual
      health topics; lesbian, gay, bisexual, transgender (LGBT) topics; teaching
      methods; and the amount of time spent on sexual health education. RESULTS: A
      total of 106 programs responded (59%). Ten programs offered a required, discrete
      course on human sexuality. The majority incorporated training into other
      coursework, which is consistent with most medical schools. LGBT topics were
      covered less thoroughly than the general sexual health topics. Total amount of
      time spent on sexual health topics varied widely among programs, from a minimum
      of 2-4 hours to a maximum of 60 hours, with a median of 12 hours. CONCLUSIONS: PA
      programs in the United States appear to compare favorably with the training
      offered to medical students in regard to time spent on sexual health education.
      Transgender issues were least well-covered of all the topics queried.

PMID- 25856227
TI  - YM155, a selective survivin inhibitor, reverses chronic hypoxic pulmonary
      hypertension in rats via upregulating voltage-gated potassium channels.
AB  - To test the hypothesis that chronic hypoxic pulmonary hypertension (CH-PH) is
      associated with increased survivin and decreased voltage-gated potassium (KV)
      channels expression in pulmonary arteries, rats were randomized as: normoxia (N);
      normoxia + YM155, survivin suppressor (NY); hypoxia (H); hypoxia + YM155 (HY). HY
      group had significantly reduced pulmonary arterial pressure, right ventricular
      weight and right ventricular hypertrophy compared with H group. Survivin mRNA and
      protein were detected in pulmonary arteries of rats with CH-PH, but not rats
      without CH-PH. YM155 downregulated survivin protein and mRNA. KV channel
      expression and activity were upregulated after YM155 treatment. Survivin may play
      a role in the pathogenesis of CH-PH. 

PMID- 25856228
TI  - A single-image method for x-ray refractive index CT.
AB  - X-ray refraction-based computer tomography imaging is a well-established method
      for nondestructive investigations of various objects. In order to perform the 3D
      reconstruction of the index of refraction, two or more raw computed tomography
      phase-contrast images are usually acquired and combined to retrieve the
      refraction map (i.e. differential phase) signal within the sample. We suggest an
      approximate method to extract the refraction signal, which uses a single raw
      phase-contrast image. This method, here applied to analyzer-based phase-contrast
      imaging, is employed to retrieve the index of refraction map of a biological
      sample. The achieved accuracy in distinguishing the different tissues is
      comparable with the non-approximated approach. The suggested procedure can be
      used for precise refraction computer tomography with the advantage of a reduction
      of at least a factor of two of both the acquisition time and the dose delivered
      to the sample with respect to any of the other algorithms in the literature. 

PMID- 25856229
TI  - A Broad Anti-influenza Hybrid Small Molecule That Potently Disrupts the
      Interaction of Polymerase Acidic Protein-Basic Protein 1 (PA-PB1) Subunits.
AB  - In continuing our efforts to identify small molecules able to disrupt the
      interaction of the polymerase acidic protein-basic protein 1 (PA-PB1) subunits of
      influenza virus (Flu) RNA-dependent RNA polymerase, this paper is devoted to the
      optimization of a dihydrotriazolopyrimidine derivative, previously identified
      through structure-based drug discovery. The structure modifications performed
      around the bicyclic core led to the identification of compounds endowed with both
      the ability to disrupt PA-PB1 subunits interaction and anti-Flu activity with no
      cytotoxicity. Very interesting results were obtained with the hybrid molecules 36
      and 37, designed by merging some peculiar structural features known to impart PA
      PB1 interaction inhibition, with compound 36 that emerged as the most potent PA
      PB1 interaction inhibitor (IC50 = 1.1 MUM) among all the small molecules reported
      so far. Calculations showed a very favored H-bonding between the 2-amidic
      carbonyl of 36 and Q408, which seems to justify its potent ability to interfere
      with the interaction of the polymerase subunits. 

PMID- 25856230
TI  - Molecular barcoding of aquatic oligochaetes: implications for biomonitoring.
AB  - Aquatic oligochaetes are well recognized bioindicators of quality of sediments
      and water in watercourses and lakes. However, the difficult taxonomic
      determination based on morphological features compromises their more common use
      in eco-diagnostic analyses. To overcome this limitation, we investigated
      molecular barcodes as identification tool for broad range of taxa of aquatic
      oligochaetes. We report 185 COI and 52 ITS2 rDNA sequences for specimens
      collected in Switzerland and belonging to the families Naididae, Lumbriculidae,
      Enchytraeidae and Lumbricidae. Phylogenetic analyses allowed distinguishing 41
      lineages separated by more than 10 % divergence in COI sequences. The lineage
      distinction was confirmed by Automatic Barcode Gap Discovery (ABGD) method and by
      ITS2 data. Our results showed that morphological identification underestimates
      the oligochaete diversity. Only 26 of the lineages could be assigned to
      morphospecies, of which seven were sequenced for the first time. Several cryptic
      species were detected within common morphospecies. Many juvenile specimens that
      could not be assigned morphologically have found their home after genetic
      analysis. Our study showed that COI barcodes performed very well as species
      identifiers in aquatic oligochaetes. Their easy amplification and good taxonomic
      resolution might help promoting aquatic oligochaetes as bioindicators for next
      generation environmental DNA biomonitoring of aquatic ecosystems. 

PMID- 25856232
TI  - Delayed fertility transition among indigenous women in the Ecuadorian Amazon.
AB  - CONTEXT: Communities indigenous to the Amazon are among the few remaining
      worldwide still practicing near-natural fertility, without the use of modern
      contraceptives. Given the large proportion of women desiring no more births,
      information on the challenges women there face in limiting fertility would be
      useful. METHODS: Samples of women of reproductive age from five indigenous ethnic
      groups in the Northern Ecuadorian Amazon were surveyed in 2001 and 2012. Cross
      sectional and longitudinal analyses examined married women's desire for another
      child at both times and modern contraceptive use in 2012, as well as determinants
      of a change in women's desire to have more children and of the number of children
      born during the study period. RESULTS: In 2001, 48% of married women desired
      another child, 2% used a modern contraceptive and 50% had an unmet need for
      limiting; in 2012, the proportions were 40%, 19% and 47%, respectively. The total
      fertility rate was 7.9 births per woman in 2001 and 7.0 births per woman in 2012.
      Characteristics associated with wanting another child in 2001 and 2012 included
      parity (odds ratios, 0.6 and 0.4, respectively) and experience of a child death
      (2.0 each); characteristics associated with contraceptive use in 2012 included
      desire for another child, experience of a child death and presence of a community
      health worker (0.3-0.5). Number of children born was positively associated, and
      the square of the term negatively associated, with no longer wanting more
      children in 2012 among women who wanted more in 2001 (2.1 and 0.9, respectively).
      CONCLUSIONS: Indigenous women in the Northern Ecuadorian Amazon appear to be
      making the transition to lower fertility. Insufficient access to credible
      information about the safety and efficacy of modern contraceptives, however, may
      slow the transition.

PMID- 25856233
TI  - Estimates of the incidence of induced abortion and consequences of unsafe
      abortion in Senegal.
AB  - CONTEXT: Abortion is highly restricted by law in Senegal. Although women seek
      care for abortion complications, no national estimate of abortion incidence
      exists. METHODS: Data on postabortion care and abortion in Senegal were collected
      in 2013 using surveys of a nationally representative sample of 168 health
      facilities that provide postabortion care and of 110 professionals knowledgeable
      about abortion service provision. Indirect estimation techniques were applied to
      the data to estimate the incidence of induced abortion in the country. Abortion
      rates and ratios were calculated for the nation and separately for the Dakar
      region and the rest of the country. The distribution of pregnancies by planning
      status and by outcome was estimated. RESULTS: In 2012, an estimated 51,500
      induced abortions were performed in Senegal, and 16,700 (32%) resulted in
      complications that were treated at health facilities. The estimated abortion rate
      was 17 per 1,000 women aged 15-44 and the abortion ratio was 10 per 100 live
      births. The rate was higher in Dakar (21 per 1,000) than in the rest of the
      country (16 per 1,000). Poor women were far more likely to experience abortion
      complications, and less likely to receive treatment for complications, than
      nonpoor women. About 31% of pregnancies were unintended, and 24% of unintended
      pregnancies (8% of all pregnancies) ended in abortion. CONCLUSIONS: Unsafe
      abortion exacts a heavy toll on women in Senegal. Reducing the barriers to
      effective contraceptive use and ensuring access to postabortion care without the
      risk of legal consequences may reduce the incidence of and complications from
      unsafe abortion.

PMID- 25856234
TI  - The effect of access to contraceptive services on injectable use and demand for
      family planning in Malawi.
AB  - CONTEXT: Previous studies have identified positive relationships between
      geographic proximity to family planning services and contraceptive use, but have
      not accounted for the effect of contraceptive supply reliability or the
      diminishing influence of facility access with increasing distance. METHODS:
      Kernel density estimation was used to geographically link Malawi women's use of
      injectable contraceptives and demand for birth spacing or limiting, as drawn from
      the 2010 Demographic and Health Survey, with contraceptive logistics data from
      family planning service delivery points. Linear probability models were run to
      identify associations between access to injectable services-measured by distance
      alone and by distance combined with supply reliability-and injectable use and
      family planning demand among rural and urban populations. RESULTS: Access to
      services was an important predictor of injectable use. The probability of
      injectable use among rural women with the most access by both measures was 7-8
      percentage points higher than among rural dwellers with the least access. The
      probability of wanting to space or limit births among urban women who had access
      to the most reliable supplies was 18 percentage points higher than among their
      counterparts with the least access. CONCLUSIONS: Product availability in the
      local service environment plays a critical role in women's demand for and use of
      contraceptive methods. Use of kernel density estimation in creating facility
      service environments provides a refined approach to linking women with services
      and accounts for both distance to facilities and supply reliability. Urban and
      rural differences should be considered when seeking to improve contraceptive
      access.

PMID- 25856235
TI  - The case for addressing gender and power in sexuality and HIV education: a
      comprehensive review of evaluation studies.
AB  - CONTEXT: Curriculum-based sexuality and HIV education is a mainstay of
      interventions to prevent STIs, HIV and unintended pregnancy among young people.
      Evidence links traditional gender norms, unequal power in sexual relationships
      and intimate partner violence with negative sexual and reproductive health
      outcomes. However, little attention has been paid to analyzing whether addressing
      gender and power in sexuality education curricula is associated with better
      outcomes. METHODS: To explore whether the inclusion of content on gender and
      power matters for program efficacy, electronic and hand searches were conducted
      to identify rigorous sexuality and HIV education evaluations from developed and
      developing countries published between 1990 and 2012. Intervention and study
      design characteristics of the included interventions were disaggregated by
      whether they addressed issues of gender and power. RESULTS: Of the 22
      interventions that met the inclusion criteria, 10 addressed gender or power, and
      12 did not. The programs that addressed gender or power were five times as likely
      to be effective as those that did not; fully 80% of them were associated with a
      significantly lower rate of STIs or unintended pregnancy. In contrast, among the
      programs that did not address gender or power, only 17% had such an association.
      CONCLUSIONS: Addressing gender and power should be considered a key
      characteristic of effective sexuality and HIV education programs.

PMID- 25856236
TI  - Integrating family planning promotion into the work of environmental volunteers:
      a population, health and environment initiative in Kenya.
AB  - Voluntary use of family planning is instrumental to the health and social well
      being of women, families and communities.Although contraceptive use in Sub
      Saharan Africa is increasing, unmet need for family planning remains high. Even
      within countries that have achieved increases in contraceptive prevalence, use
      remains low among some population subgroups. Contraceptive prevalence is
      generally lower in rural areas than in cities, and is consistently lower among
      women in the lowest wealth quintile than among those in the highest. Achieving
      progress in health and social indicators, such as those captured by the
      Millennium Development Goals, depends on expanding family planning services to
      poor, remote rural areas in Africa. 

PMID- 25856231
TI  - Five-year incidence of chronic kidney disease (stage 3-5) and associated risk
      factors in a Spanish cohort: the MADIABETES Study.
AB  - OBJECTIVE: To evaluate the incidence rate of Chronic Kidney Disease (CKD) stage 3
      5 (persistent decreased kidney function under 60 mL/min per 1.73 m2) among
      patients with type 2 diabetes over five years, to identify the risk factors
      associated with CKD, and develop a risk table to predict five-year CKD stage 3-5
      risk stratification for clinical use. DESIGN: The MADIABETES Study is a
      prospective cohort study of 3,443 outpatients with type 2 diabetes mellitus,
      sampled from 56 primary health care centers (131 general practitioners) in Madrid
      (Spain). RESULTS: The cumulative incidence of CKD stage 3-5 at five-years was
      10.23% (95% CI = 9.12-11.44) and the incidence density was 2.07 (95% CI = 1.83
      2.33) cases per 1,000 patient-months or 2.48 (95% CI = 2.19-2.79) cases per 100
      patient-years. The highest hazard ratio (HR) for developing CKD stage 3-5 was
      albuminuria >= 300 mg/g (HR = 4.57; 95% CI= 2.46-8.48). Furthermore, other
      variables with a high HR were age over 74 years (HR = 3.20; 95% CI = 2.13-4.81),
      a history of Hypertension (HR = 2.02; 95% CI = 1.42-2.89), Myocardial Infarction
      (HR= 1.72; 95% IC= 1.25-2.37), Dyslipidemia (HR = 1.68; 95% CI 1.30-2.17),
      duration of diabetes mellitus >= 10 years (HR = 1.46; 95% CI = 1.14-1.88) and
      Systolic Blood Pressure >149 mmHg (HR = 1.52; 95% CI = 1.02-2.24). CONCLUSIONS:
      After a five-year follow-up, the cumulative incidence of CKD is concordant with
      rates described in Spain and other countries. Albuminuria >= 300 mg/g and age
      over 74 years were the risk factors more strongly associated with developing CKD
      (Stage 3-5). Blood Pressure, lipid and albuminuria control could reduce CKD
      incidence of CKD in patients with T2DM.

PMID- 25856237
TI  - Metabolomics analysis and biomarker identification for brains of rats exposed
      subchronically to the mixtures of low-dose cadmium and chlorpyrifos.
AB  - Cadmium (Cd) and chlorpyrifos (CPF) are widespread harmful environmental
      pollutants with neurotoxicity to mammals. Although the exposure to Cd and CPF at
      the same time may pose a significant risk to human health, the subchronic
      combined neurotoxicity of these two chemicals at low levels in the brain is
      poorly understood. In this study, we treated rats with three doses (low, middle,
      and high) of Cd, CPF, or their mixture for 90 days. No obvious symptom was
      observed in the treated animals except those treated with high-dose CPF.
      Histological results showed that middle and high doses of the chemicals caused
      neuronal cell damage in brains. GC-MS-based metabonomics analysis revealed that
      energy and amino acid metabolism were disturbed in the brains of rats exposed to
      the two chemicals and their combinations even at low doses. We further identified
      the unique brain metabolite biomarkers for rats treated with Cd, CPF, or both.
      Two amino acids, tyrosine and l-leucine, were identified as the biomarkers for Cd
      and CPF treatment, respectively. In addition, a set of five unique biomarkers
      (1,2-propanediol-1-phosphate, d-gluconic acid, 9H-purine, serine, and 2
      ketoisovaleric acid) was identified for the mixtures of Cd and CPF. Therefore,
      the metabolomics analysis is more sensitive than regular clinical observation and
      pathological examination for detecting the neurotoxicity of the individual and
      combined Cd and CPF at low levels. Overall, these results identified the unique
      biomarkers for Cd and CPF exposure, which provide new insights into the mechanism
      of their joint toxicity.

PMID- 25856238
TI  - Long-lasting insecticidal nets to prevent visceral leishmaniasis in the Indian
      subcontinent; methodological lessons learned from a cluster randomised controlled
      trial.

PMID- 25856239
TI  - Voltage-dependent K+ currents contribute to heterogeneity of olfactory
      ensheathing cells.
AB  - The olfactory nerve is permissive for axon growth throughout life. This has been
      attributed in part to the olfactory ensheathing glial cells that encompass the
      olfactory sensory neuron fascicles. Olfactory ensheathing cells (OECs) also
      promote axon growth in vitro and when transplanted in vivo to sites of injury.
      The mechanisms involved remain largely unidentified owing in part to the limited
      knowledge of the physiological properties of ensheathing cells. Glial cells rely
      for many functions on the properties of the potassium channels expressed;
      however, those expressed in ensheathing cells are unknown. Here we show that OECs
      express voltage-dependent potassium currents compatible with inward rectifier
      (Kir ) and delayed rectifier (KDR ) channels. Together with gap junction
      coupling, these contribute to the heterogeneity of membrane properties observed
      in OECs. The relevance of K(+) currents expressed by ensheathing cells is
      discussed in relation to plasticity of the olfactory nerve.

PMID- 25856240
TI  - Distinct sensitivities to phosphate deprivation suggest that RGF peptides play
      disparate roles in Arabidopsis thaliana root development.
AB  - Growing agricultural demands in the face of impending inorganic phosphate (Pi)
      shortages underscore a need for a better understanding of plant development under
      conditions of Pi deprivation. Pi is an essential nutrient that is a major
      component of fertilizer. Plants have evolved strategies to improve the
      acquisition of this nutrient by altering root development under shortage
      conditions. We show that signaling peptides thought to act redundantly in
      Arabidopsis thaliana development have distinct functions in response to Pi
      deprivation. Using microscopy and confocal imaging, roots were analyzed for
      growth rate and cellular composition. Using expression microarrays, genes
      influencing development in response to phosphate deprivation were identified.
      ROOT GROWTH FACTOR1 (RGF1) and RGF2 influenced different aspects of root
      development under conditions of Pi deprivation. We found that RGF2 influenced the
      longitudinal growth rate in the primary root in response to Pi deprivation,
      whereas RGF1 affected circumferential cell number in the root meristem. These
      data suggest that the mechanisms controlling adaptive development can depend on
      disparate functions of genes thought to act redundantly, thus elucidating new
      functions for important developmental regulators. 

PMID- 25856241
TI  - Predicting plant diversity patterns in Madagascar: understanding the effects of
      climate and land cover change in a biodiversity hotspot.
AB  - Climate and land cover change are driving a major reorganization of terrestrial
      biotic communities in tropical ecosystems. In an effort to understand how
      biodiversity patterns in the tropics will respond to individual and combined
      effects of these two drivers of environmental change, we use species distribution
      models (SDMs) calibrated for recent climate and land cover variables and
      projected to future scenarios to predict changes in diversity patterns in
      Madagascar. We collected occurrence records for 828 plant genera and 2186 plant
      species. We developed three scenarios, (i.e., climate only, land cover only and
      combined climate-land cover) based on recent and future climate and land cover
      variables. We used this modelling framework to investigate how the impacts of
      changes to climate and land cover influenced biodiversity across ecoregions and
      elevation bands. There were large-scale climate- and land cover-driven changes in
      plant biodiversity across Madagascar, including both losses and gains in
      diversity. The sharpest declines in biodiversity were projected for the eastern
      escarpment and high elevation ecosystems. Sharp declines in diversity were driven
      by the combined climate-land cover scenarios; however, there were subtle, region
      specific differences in model outputs for each scenario, where certain regions
      experienced relatively higher species loss under climate or land cover only
      models. We strongly caution that predicted future gains in plant diversity will
      depend on the development and maintenance of dispersal pathways that connect
      current and future suitable habitats. The forecast for Madagascar's plant
      diversity in the face of future environmental change is worrying: regional
      diversity will continue to decrease in response to the combined effects of
      climate and land cover change, with habitats such as ericoid thickets and eastern
      lowland and sub-humid forests particularly vulnerable into the future. 

PMID- 25856242
TI  - In-situ formation of hollow hybrids composed of cobalt sulfides embedded within
      porous carbon polyhedra/carbon nanotubes for high-performance lithium-ion
      batteries.
AB  - 3D hollow hybrid composites with ultrafine cobalt sulfide nanoparticles uniformly
      embedded within the well-graphitized porous carbon polyhedra/carbon nanotubes
      framework are rationally fabricated using a green and one-step method involving
      the simultaneous pyrolysis and sulfidation of ZIF-67. Because of the synergistic
      coupling effects favored by the unique nanohybridization, these composites
      exhibit high specific capacity, excellent cycle stability, and superior rate
      capability when evaluated as electrodes in lithium-ion batteries. 

PMID- 25856243
TI  - Supplementary home biofeedback improves quality of life in younger patients with
      fecal incontinence.
AB  - BACKGROUND: Biofeedback is a scarce, resource-intensive clinical therapy. It is
      used to treat patients with bowel problems, including fecal incontinence (FI),
      who fail to respond to simple dietary advice, medication, or pelvic floor
      exercises. Populations are aging and younger cohorts use technology in managing
      their health, affording FI self-management opportunities. AIM: Does supplementary
      home-based biofeedback improve FI and quality of life (QOL)? METHODS: Seventy
      five incontinent participants (12 male), mean age 61.1 years, consented to
      participate. Thirty-nine patients (5 male) were randomized to the standard
      biofeedback protocol plus daily home use of a Peritron perineometer
      (intervention) and 36 patients (7 male) to the standard biofeedback protocol
      (control). On completion of the study each perineometer exercise session was
      rated for technique by 2 raters, blinded to the patient and order of sessions.
      RESULTS: With the exception of Fecal Incontinence Quality of Life Scale lifestyle
      improvement (intervention--9.1% vs. controls--0.3%, P=0.026) and embarrassment
      improvement (intervention--50.0% vs. controls--18.3%, P=0.026), supplementary
      home biofeedback did not result in greater clinical improvement for the
      intervention group as a whole. However, on stratification around the mean age,
      continence and QOL of younger people in the intervention group were significantly
      better than those of their control counterparts. Graphed perineometer sessions
      demonstrated high compliance and improvement in exercise technique. Perineometers
      provided reassurance, motivation, and an exercise reminder ensuring that
      confidence was achieved quickly. CONCLUSIONS: Home biofeedback was acceptable and
      well tolerated by all users. Younger participants significantly benefited from
      using this technology.

PMID- 25856244
TI  - Spin propensities of octahedral complexes from density functional theory.
AB  - The fundamental balance between high- and low-spin states of transition metal
      systems depends on both the metal ion and the ligands surrounding it, as often
      visualized by the spectrochemical series. Most density functionals do not
      reproduce this balance, and real spin state propensities depend on orbital
      pairing and vibrational entropies absent in the spectrochemical series. Thus, we
      systematically computed the tendency toward high or low spin of "text-book"
      octahedral metal complexes versus ligand and metal type, using eight density
      functionals. Dispersion effects were generally <5 kJ/mol, favoring low-spin
      states. Zero-point energies favored high-spin states up to 33 kJ/mol for strong
      ligands, but down to a few kilojoules per mole for weak ligands. Vibrational
      entropy also favored high-spin states up to 40 kJ/mol, most for strong ligands.
      Jahn-Teller distortion in Co(II) low-spin states, particularly stable d(6) low
      spin states, and entropy corrections were consistent with experiment. Entropy and
      zero-point energy corrections were markedly lower for Co(II) and Mn(III), viz.,
      the differential ligand field stabilization energy, and can only be ignored for
      weak ligands. The data enable simple assessment of spin state propensities versus
      ligand and metal type and reveal, e.g., that CN(-) is consistently weaker than CO
      for M(II) but stronger than CO for M(III) and SCN(-) and NCS(-) change order in
      M(II) versus M(III) complexes. Contrary to expectation based on the
      spectrochemical series, Cl(-) and Br(-) are very close in spin state propensity
      because the pairing penalty for low spin is smaller in Br(-). Thus, for the M(II)
      complexes, we find a consensus order of Br(-) ~ Cl(-) < H2O < SCN(-) < NCS(-) ~
      NH3 < CN(-) < CO, whereas for the M(III) complexes, an approximate order is Br(-)
      ~ Cl(-) < H2O ~ NCS(-) ~ SCN(-)< NH3 < CO < CN(-). 

PMID- 25856245
TI  - Integrating emerging treatment options in mantle cell lymphoma: introduction.
AB  - Mantle cell lymphoma (MCL) is a unique subtype of non-Hodgkin lymphoma (NHL). MCL
      accounts for approximately 6% of new lymphoma cases each year.1 Because it is a
      relatively uncommon form of lymphoma, it is more difficult to study than other
      lymphoma subtypes. There are many single-arm, phase 2 trials in the MCL
      literature, but there is a relative paucity of large, randomized, phase 3 trials.
      As a result, comparisons are often made across trials, and observations are based
      on extrapolation. 

PMID- 25856246
TI  - Frontline management strategies for younger, fit patients with mantle cell
      lymphoma.

PMID- 25856247
TI  - Frontline management strategies for older MCL patients.

PMID- 25856249
TI  - Integrating emerging treatment options in mantle cell lymphoma: general
      discussion.

PMID- 25856248
TI  - Management strategies for relapsed/refractory MCL.

PMID- 25856250
TI  - Values as Moderators of the Association between Interpersonal-Psychological
      Constructs and Suicidal Ideation among Veterans.
AB  - This study examined whether valuing relationships, achievement, and security
      moderated the association between interpersonal-psychological constructs (Joiner,
      2005) and suicidal ideation (SI). A total of 122 veterans completed the
      Interpersonal Needs Questionnaire, Survey of Life Principles, and Beck Scale for
      Suicide Ideation. Valuing relationships moderated the association between
      thwarted belongingness and SI. Specifically, thwarted belongingness predicted SI
      among veterans who reported moderate and high, but not low, levels of valuing
      relationships. The estimated impact of perceived burdensomeness on SI was
      stronger at higher levels of valuing relationships, but only approached
      statistical significance. Valuing achievement and security did not moderate the
      association between perceived burdensomeness and SI. Future research should
      continue to examine specific values as they relate to interpersonal-psychological
      constructs and suicidal behavior.

PMID- 25856251
TI  - Diagnosis and management of hyponatraemia: AGREEing the guidelines.
AB  - Hyponatraemia is a common electrolyte disorder associated with significant
      complications and controversies regarding its optimal management. Clinical
      practice guidelines and consensus statements have attempted to provide clinicians
      with evidence-based diagnostic and treatment strategies for hyponatraemia.
      Recently published guidance documents differ in their methods employed to review
      the quality of available evidence. Nagler et al. used the Appraisal of Guideline
      for Research and Evaluation (AGREE II) instrument in a systematic review of
      guidelines and consensus statements for the diagnosis and management of
      hyponatraemia. Nagler and colleagues highlighted the variability in
      methodological rigour applied to guideline development and inconsistencies
      between publications in relation to management of hyponatraemia (including the
      recommended rate of correction of a low serum sodium concentration). These
      differences could cause confusion for practising physicians managing patients
      with hyponatraemia. Please see related article: http://www.biomedcentral.com/1741
      7015/12/231.

PMID- 25856253
TI  - Sustained decrease in laboratory detection of rotavirus after implementation of
      routine vaccination-United States, 2000-2014.
AB  - Rotavirus infection is the leading cause of severe gastroenteritis among infants
      and young children worldwide. Before the introduction of rotavirus vaccine in the
      United States in 2006, rotavirus infection caused significant morbidity among
      U.S. children, with an estimated 55,000-70,000 hospitalizations and 410,000
      clinic visits annually. The disease showed a characteristic winter-spring
      seasonality and geographic pattern, with annual seasonal activity beginning in
      the West during December-January, extending across the country, and ending in the
      Northeast during April-May. To characterize changes in rotavirus disease trends
      and seasonality following introduction of rotavirus vaccines in the United
      States, CDC compared data from CDC's National Respiratory and Enteric Virus
      Surveillance System (NREVSS), a passive laboratory reporting system, for
      prevaccine (2000-2006) and postvaccine (2007-2014) years. National declines in
      rotavirus detection were noted, ranging from 57.8%-89.9% in each of the 7
      postvaccine years compared with all 7 prevaccine years combined. A biennial
      pattern of rotavirus activity emerged in the postvaccine era, with years of low
      activity and highly erratic seasonality alternating with years of moderately
      increased activity and seasonality similar to that seen in the prevaccine era.
      These results demonstrate the substantial and sustained effect of rotavirus
      vaccine in reducing the circulation and changing the epidemiology of rotavirus
      among U.S. children. 

PMID- 25856252
TI  - Self-reported Calcium Supplementation and Age-Related Macular Degeneration.
AB  - IMPORTANCE: Despite widespread use of calcium supplementation among elderly
      people, little is known about the association between such consumption and the
      prevalence of age-related macular degeneration (AMD) in the United States.
      OBJECTIVE: To investigate the association between self-reported supplementary
      calcium consumption and the prevalence of AMD in a representative US sample.
      DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study included 3191
      participants 40 years and older in the 2007-2008 National Health and Nutrition
      Examination Survey (NHANES) who were evaluated for the presence or absence of AMD
      by fundus photography. Participants were interviewed regarding use of dietary
      supplements and antacids during the 30-day period preceding enrollment. Self
      reported supplementary intake of calcium was aggregated and divided into
      quintiles. Fundus photographs were graded for the presence or absence of AMD.
      Information regarding demographics, comorbidities, and health-related behaviors
      was obtained via interview. Multivariable logistic regression models were created
      to determine the odds of an AMD diagnosis among participants in each quintile of
      self-reported calcium vs participants not self-reporting supplementary calcium
      consumption after adjusting for confounders. INTERVENTIONS: Self-reported use of
      calcium supplements. MAIN OUTCOMES AND MEASURES: Presence or absence of AMD by
      fundus photography. RESULTS: A total of 248 participants (7.8%) were diagnosed
      with AMD. Mean ages were 67.2 years for those with AMD and 55.8 for those without
      AMD. After adjustment for potential confounding variables, study participants who
      self-reported consumption of more than 800 mg/d of supplementary calcium were
      found to have higher odds of an AMD diagnosis based on fundus photography
      evaluation compared with those not self-reporting supplementary calcium
      consumption (odds ratio, 1.85; 95% CI, 1.25-2.75). The association between self
      reported supplementary calcium intake and AMD was stronger in older than younger
      individuals (odds ratio, 2.63; 95% CI, 1.52-4.54). A clear dose-response
      association between the quintiles of self-reported supplementary calcium intake
      and AMD was not established. CONCLUSIONS AND RELEVANCE: Self-reported
      supplementary calcium consumption is associated with increased prevalence of AMD,
      with the findings suggesting a threshold rather than a dose-response
      relationship. The stronger association in older individuals may be due to
      relatively longer duration of calcium supplementation in older individuals.

PMID- 25856254
TI  - Work-related asthma-22 states, 2012.
AB  - Work-related asthma (WRA) is a preventable occupational disease associated with
      serious adverse health outcomes. Using the 2006-2009 Behavioral Risk Factor
      Surveillance System (BRFSS) Adult Asthma Call-back Survey (ACBS) data from 38
      states and the District of Columbia, CDC estimated that among ever-employed
      adults with current asthma, the proportion of current asthma that is work-related
      was 9.0%. In 2011, the BRFSS cellular telephone samples were added to the
      traditional landline telephone samples and the weighting methodology was changed.
      In 2012, a revised ACBS question on WRA diagnosis was asked. To provide updated
      estimates of current asthma prevalence and the proportion of asthma that is work
      related, by state, CDC analyzed data from BRFSS and ACBS collected from 22 states
      using both landline and cellular telephone samples during 2012. This report
      summarizes the results of that analysis, which indicate that 9.0% of adults had
      current asthma and that among ever-employed adults with current asthma, the
      overall proportion of current asthma that is work-related was 15.7%. State
      specific proportions of asthma that is work-related ranged from 9.0% to 23.1%.
      Distribution of the proportion of WRA significantly differed by age and was
      highest among persons aged 45-64 years (20.7%). These findings provide a new
      baseline after the implementation of changes in survey methodology and the
      adoption of a revised WRA question. These results can assist states, other
      government agencies, health professionals, employers, workers, and worker
      representatives to better target intervention and prevention efforts to reduce
      the burden of WRA.

PMID- 25856255
TI  - Ebola active monitoring system for travelers returning from West Africa-Georgia,
      2014-2015.
AB  - The Ebola virus disease (Ebola) epidemic in West Africa has so far produced
      approximately 25,000 cases, more than 40 times the number in any previously
      documented Ebola outbreak. Because of the risk for imported disease from infected
      travelers, in October 2014 CDC recommended that all travelers to the United
      States from Ebola-affected countries receive enhanced entry screening and
      postarrival active monitoring for Ebola signs or symptoms until 21 days after
      their departure from an Ebola-affected country. The state of Georgia began its
      active monitoring program on October 25, 2014. The Georgia Department of Public
      Health (DPH) modified its existing, web-based electronic notifiable disease
      reporting system to create an Ebola Active Monitoring System (EAMS). DPH staff
      members developed EAMS from conceptualization to implementation in 6 days. In
      accordance with CDC recommendations, "low (but not zero) risk" travelers are
      required to report their daily health status to DPH, and the EAMS dashboard
      enables DPH epidemiologists to track symptoms and compliance with active
      monitoring. Through March 31, 2015, DPH monitored 1,070 travelers, and 699 (65%)
      used their EAMS traveler login instead of telephone or e-mail to report their
      health status. Medical evaluations were performed on 30 travelers, of whom three
      were tested for Ebola. EAMS has enabled two epidemiologists to monitor
      approximately 100 travelers daily, and to rapidly respond to travelers reporting
      signs and symptoms of potential Ebola virus infection. Similar electronic
      tracking systems might be useful for other jurisdictions.

PMID- 25856256
TI  - Progress in identifying infants with hearing loss-United States, 2006-2012.
AB  - Congenital hearing loss affects one to three of every 1,000 live born infants and
      negatively impacts children through delayed speech, language, social, and
      emotional development when undetected. To address this public health issue,
      jurisdiction-based Early Hearing Detection and Intervention (EHDI) programs are
      working to ensure all newborns are screened for hearing loss, receive follow-up
      diagnostic testing (DX) if they do not pass the screening, and are enrolled in
      early intervention (EI) services if diagnosed with a permanent hearing loss.
      Although substantial progress has been made in the provision and documentation of
      services, challenges remain because, unlike screening results, diagnostic test
      results and enrollment in EI are not consistently reported to the EHDI programs.
      Therefore, it is difficult for states and territories to know if infants received
      recommended follow-up services (diagnostic testing and/or EI services), often
      resulting in infants being classified at either stage as lost to follow-up
      (LFU)/lost to documentation (LTD). To assess progress toward identifying children
      with hearing loss and reducing LFU/LTD for DX (LFU/LTD-DX) and EI enrollment
      (LFU/LTD-EI), CDC analyzed EHDI surveillance data for 2006-2012. Results
      indicated that the number of jurisdictions reporting data increased from 49 to
      57, rates of screening increased from 95.2% to 96.6%, rates of referral from
      screening decreased from 2.3% to 1.6%, rates of diagnosis among infants not
      passing their final screening increased from 4.8% to 10.3%, and enrollment in EI
      among children diagnosed with hearing loss increased from 55.4% to 61.7%, whereas
      rates for both LFU/LTD-DX and LFU/LTD-EI declined. These findings show sustained
      progress toward screening, identification, and enrollment in EI as well as
      highlighting the need for continued improvements in the provision and
      documentation of EHDI services.

PMID- 25856257
TI  - Progress toward measles elimination-Philippines, 1998-2014.
AB  - In 2005, the Regional Committee for the World Health Organization (WHO) Western
      Pacific Region (WPR) established a goal to eliminate measles by 2012.The
      recommended elimination strategies in WPR include 1) >=95% 2-dose coverage with
      measles-containing vaccine (MCV) through routine immunization services and
      supplementary immunization activities (SIAs); 2) high-quality case-based measles
      surveillance; 3) laboratory surveillance with timely and accurate testing of
      specimens to confirm or discard suspected cases and detect measles virus
      genotypes; and 4) measles outbreak preparedness, rapid response, and appropriate
      case management. In the WPR, the Philippines set a national goal in 1998 to
      eliminate measles by 2008. This report describes progress toward measles
      elimination in the Philippines during 1998-2014 and challenges remaining to
      achieve the goal. WHO-United Nations Children's Fund (UNICEF)-estimated coverage
      with the routine first dose of MCV (MCV1) increased from 80% in 1998 to 90% in
      2013, and coverage with the routine second dose of MCV (MCV2) increased from 10%
      after nationwide introduction in 2010 to 53% in 2013. After nationwide SIAs in
      1998 and 2004, historic lows in the numbers and incidence of reported measles
      cases occurred in 2006. Despite nationwide SIAs in 2007 and 2011, the number of
      reported cases and incidence generally increased during 2007-2012, and large
      measles outbreaks occurred during 2013-2014 that affected infants, young
      children, older children, and young adults and that were prolonged by delayed and
      geographically limited outbreak response immunization activities during 2013
      2014. For the goal of measles elimination in WPR to be achieved, sustained
      investments are required in the Philippines to strengthen health systems,
      implement the recommended elimination strategies, and develop additional
      strategies to identify and reduce measles susceptibility in specific geographic
      areas and older age groups.

PMID- 25856258
TI  - Vital signs: trends in use of long-acting reversible contraception among teens
      aged 15-19 years seeking contraceptive services-United States, 2005-2013.
AB  - BACKGROUND: Nationally, the use of long-acting reversible contraception (LARC),
      specifically intrauterine devices (IUDs) and implants, by teens remains low,
      despite their effectiveness, safety, and ease of use. METHODS: To examine
      patterns in use of LARC among females aged 15-19 years seeking contraceptive
      services, CDC and the U.S. Department of Health and Human Services' Office of
      Population Affairs analyzed 2005-2013 data from the Title X National Family
      Planning Program. Title X serves approximately 1 million teens each year and
      provides family planning and related preventive health services for low-income
      persons. RESULTS: Use of LARC among teens seeking contraceptive services at Title
      X service sites increased from 0.4% in 2005 to 7.1% in 2013 (p-value for trend
      <0.001). Of the 616,148 female teens seeking contraceptive services in 2013,
      17,349 (2.8%) used IUDs, and 26,347 (4.3%) used implants. Use of LARC was higher
      among teens aged 18-19 years (7.6%) versus 15-17 years (6.5%) (p<0.001). The
      percentage of teens aged 15-19 years who used LARC varied widely by state, from
      0.7% (Mississippi) to 25.8% (Colorado). CONCLUSIONS: Although use of LARC by
      teens remains low nationwide, efforts to improve access to LARC among teens
      seeking contraception at Title X service sites have increased use of these
      methods. IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Health centers that provide
      quality contraceptive services can facilitate use of LARC among teens seeking
      contraception. Strategies to address provider barriers to offering LARC include:
      1) educating providers that LARC is safe for teens; 2) training providers on LARC
      insertion and a client-centered counseling approach that includes discussing the
      most effective contraceptive methods first; and 3) providing contraception at
      reduced or no cost to the client.

PMID- 25856259
TI  - An 8-Year-Old Child with Malignant Deciduoid Mesothelioma of the Abdomen: Report
      of a Case and Review of the Literature.
AB  - Malignant mesothelioma is an uncommon tumor that usually arises in the pleural
      cavity of adults with a history of asbestos exposure. Less frequently, it appears
      in the peritoneum or other mesothelial surfaces. Deciduoid mesothelioma is a rare
      subtype that has been found at both sites. Of the 3 reported cases in children, 2
      originated in the mesenterium and 1 in the pleura. We describe a 4th case of
      pediatric, malignant, deciduoid mesothelioma and a third case in the mesenteric
      cavity. The patient was an 8-year-old girl who presented with abdominal pain and
      fullness. Workup revealed extensive involvement of the abdomen by a serosa-based
      tumor. The clinical and pathologic findings are described, and the pertinent
      literature is reviewed. 

PMID- 25856260
TI  - Polypyrrole-MnO2-Coated Textile-Based Flexible-Stretchable Supercapacitor with
      High Electrochemical and Mechanical Reliability.
AB  - Carbon-nanotube (CNT)-based textile supercapacitors with MnO2 nanoparticles have
      excellent power and energy densities, but MnO2 nanoparticles can be delaminated
      during charge-discharge cycles, which results in significant degradation in
      capacitance. In this study, polypyrrole conductive polymer was coated on top of
      MnO2 nanoparticles that are deposited on CNT textile supercapacitor to prevent
      delamination of MnO2 nanoparticles. An increase of 38% in electrochemical energy
      capacity to 461 F/g was observed, while cyclic reliability also improved, as
      93.8% of energy capacity was retained over 10 000 cycles. Energy density and
      power density were measured to be 31.1 Wh/kg and 22.1 kW/kg, respectively. An in
      situ electrochemical-mechanical study revealed that polypyrrole-MnO2-coated CNT
      textile supercapacitor can retain 98.5% of its initial energy capacity upon
      application of 21% tensile strain and showed no observable energy storage
      capacity change upon application of 13% bending strain. After imposing cyclic
      bending of 750 000 cycles, the capacitance was retained to 96.3%. Therefore, the
      results from this study confirmed for the first time that the polypyrrole-MnO2
      coated CNT textile can reliably operate with high energy and power densities with
      in situ application of both tensile and bending strains. 

PMID- 25856261
TI  - Undertapping of Lumbar Pedicle Screws Can Result in Tapping With a Pitch That
      Differs From That of the Screw, Which Decreases Screw Pullout Force.
AB  - STUDY DESIGN: Survey of spine surgeons and biomechanical comparison of screw
      pullout forces. OBJECTIVE: To investigate what may be a suboptimal practice
      regularly occurring in spine surgery. SUMMARY OF BACKGROUND DATA: In order for a
      tap to function in its intended manner, the pitch of the tap should be the same
      as the pitch of the screw. Undertapping has been shown to increase the pullout
      force of pedicle screws compared with line-to-line tapping. However, given the
      way current commercial lumbar pedicle screw systems are designed, undertapping
      may result in a tap being used that has a different pitch from that of the screw
      (incongruent pitch). METHODS: A survey asked participants questions to estimate
      the proportion of cases each participant performed in the prior year using
      various hole preparation techniques. Participant responses were interpreted in
      the context of manufacturing specifications of specific instrumentation systems.
      Screw pullout forces were compared between undertapping with incongruent pitch
      and undertapping with congruent pitch using 0.16 g/cm polyurethane foam block and
      6.5-mm screws. RESULTS: Of the 3679 cases in which participants reported tapping,
      participants reported line-to-line tapping in 209 cases (5%), undertapping with
      incongruent pitch in 1156 cases (32%), and undertapping with congruent pitch in
      2314 cases (63%). The mean pullout force for undertapping with incongruent pitch
      was 56 N (8%) less than the mean pullout force for undertapping with congruent
      pitch. This is equivalent to 13 lb. CONCLUSION: This study estimates that for
      about 1 out of every 3 surgical cases with tapping of lumbar pedicle screws in
      the United States, hole preparation is being performed by undertapping with
      incongruent pitch. This study also shows that undertapping with incongruent pitch
      results in a decrease in pullout force by 8% compared with undertapping with
      congruent pitch. Steps should be taken to correct this suboptimal practice. LEVEL
      OF EVIDENCE: 3.

PMID- 25856262
TI  - Risk Factors Associated With 30-day Readmissions After Instrumented Spine Surgery
      in 14,939 Patients: 30-day readmissions after instrumented spine surgery.
AB  - STUDY DESIGN: A retrospective review of instrumented spine registry from an
      integrated US healthcare system. OBJECTIVE: Investigate the 30-day readmission
      rate and risk factors after instrumented spine surgery. SUMMARY OF BACKGROUND
      DATA: Published readmission rates range from 2% to over 20%. We were interested
      in learning which patients were at greatest risk, when did readmissions occur,
      and why. METHOD: 30-day readmission rates were determined for 14,939 patients
      after an index spine procedure between 1/2009 and 3/2013. Data were analyzed with
      descriptive statistics, univariate, and multivariate logistic regression
      analysis. RESULT: The average age of the cohort was 59 (SD = 13.4) and 52% were
      female. The 30-day readmission rate was 5.5% (821/14,939). The temporal pattern
      for readmission was: 17% (140) at week 1, 48% (394) at week 2, 72% (591) at week
      3, and 100% (821) at week 4. The leading causes were wound complications
      (infection, hematoma, dehiscence, seroma), sepsis, pain management, pneumonia,
      and pulmonary emboli/deep venous thrombosis. In a multivariate model, readmission
      risk factors were: malignancy (OR 2.99, 95% CI: 1.56, 5.73), operative time more
      than 400 minutes (OR 2.59, 95% CI: 1.66, 4.02), operative time 300-399 minutes
      (OR 2.33, 95% CI: 1.54-3.52), hospital stay 6-10 days (OR 2.03, 95% CI: 1.31
      3.14), hospital stay more than 10 days (OR 1.85, 95% CI: 1.1, -3.08), surgical
      complications (OR 1.67, 95% CI: 1.18, 2.36), operative time 200-299 (OR 1.52, 95%
      CI: 1.04, 2.22), depression (OR 1.48, 95% CI: 1.14, 1.93), rheumatoid arthritis
      (OR 1.45, 95% CI: 1.05, 2.01), deficiency anemia (OR 1.30, 95% CI: 1.05, 1.61),
      and hypothyroidism (OR 1.29, 95% CI: 1.01, 1.64). CONCLUSION: Surgical
      complications (dural tear, deep infections, superficial infections, epidural
      hematoma), malignancy, lengthy operative times, and lengthy initial
      hospitalizations are all risk factors for 30-day readmission. These findings
      should be considered during preoperative assessment and surgical planning. LEVEL
      OF EVIDENCE: 3.

PMID- 25856264
TI  - No Effects of Hyperosmolar Culture Medium on Tissue Regeneration by Human
      Degenerated Nucleus Pulposus Cells Despite Upregulation Extracellular Matrix
      Genes.
AB  - STUDY DESIGN: An in vitro study using human degenerated nucleus pulposus cells.
      OBJECTIVE: To determine the effect of osmolality and different osmolytes on the
      regeneration by human nucleus pulposus cells through gene expression and
      extracellular matrix production. SUMMARY OF BACKGROUND DATA: Intervertebral disc
      (IVD) degeneration is a major problem in developed countries. Regeneration of the
      IVD can prevent pain and costs due to diminished work absence and health care,
      and improve quality of life. The osmotic value of a disc decreases during
      degeneration due to loss of proteoglycans and might increase degeneration. It is
      known that gene expression of matrix genes of nucleus pulposus (NP) cells
      increases when cultured in hyperosmotic medium. Thus, increasing the osmolality
      of the disc might be beneficial for disc regeneration. METHODS: In the current
      study, isolated degenerated human NP cells were used in regeneration culture with
      medium of different osmolalities, adjusted with different osmolytes. NaCl, urea
      and sucrose. The cells were cultured for 28 days and expression of matrix genes
      and production of glycosaminoglycans and collagen II were measured. RESULTS: Gene
      expression for both collagen II and aggrecan increased with increasing osmolality
      using NaCl or sucrose, but not urea. Protein production however, was not affected
      by increasing osmolality and was decreased when using urea and sucrose.
      Expression of genes for Col1A1, MMP13, and MMP14 decreased with increasing
      osmolality, whereas expression of LOXL2 and LOXL3 increased. Transient expression
      of TonEBP was found 6 hours after the start of culture, but not at later time
      points. CONCLUSION: Although expression of matrix genes is upregulated,
      hyperosmolality does not enhance matrix production by nucleus pulposus cells.
      Raising osmolality can potentially increase matrix production, but in itself is
      not sufficient to accomplish regeneration in the current in vitro culture system.
      LEVEL OF EVIDENCE: N /A.

PMID- 25856263
TI  - Paraspinal Muscle Spindle Response to Intervertebral Fixation and Segmental
      Thrust Level During Spinal Manipulation in an Animal Model.
AB  - STUDY DESIGN: In vivo cat model study. OBJECTIVE: To determine whether
      intervertebral facet joint fixation and segmental thrust level alter paraspinal
      muscle spindle activity during simulated spinal manipulation. SUMMARY OF
      BACKGROUND DATA: Intervertebral motion is commonly assessed by manual therapy
      practitioners during clinical evaluation and treatment. Mechanoreceptor activity
      elicited during spinal manipulation has been theorized as a potential mechanism
      of its efficacy. The degree to which intervertebral fixation and segmental thrust
      level alter paraspinal muscle spindle activity during high velocity low amplitude
      spinal manipulation (HVLA-SM) is unclear. METHODS: Intervertebral fixation was
      created by inserting facet screws through the left L(5-6) and L(6-7) and left L(4
      5), L(5-6), and L(6-7) facet joints of a cat spine. Changes in the mean
      instantaneous frequency of L6 muscle spindle discharge were determined during 5
      HVLA-SM thrust durations (0-control, 75, 100, 150, 250 ms) delivered at the L4 or
      L6 spinous process in each of the 3 conditions within the same preparation:
      laminectomy-only (surgical control; n = 23), L(5-6) and L(6-7) fixations (n =
      20), and L(4-5), L(5-6), and L(6-7) fixations (n = 7). Comparisons were made
      between thrust levels, thrust durations, and spinal joint conditions using a
      linear mixed model. RESULTS: Insertion of facet screws compared with laminectomy
      only significantly increased (P < 0.001) lumbar spinal stiffness during L6 HVLA
      SM. Compared with laminectomy-only, both the 2 facet screw (100 ms; P < 0.05) and
      3 screw conditions [75 ms and 100 ms (P < 0.001), 150 ms (P < 0.005), and 250 ms
      (P < 0.05)] significantly decreased L6 spindle response during the L6 HVLA-SM.
      HVLA-SM-delivered 2 segments rostral to the level of muscle spindle input
      significantly decreases spindle response compared with HVLA-SM-delivered at
      level; however, nontarget HVLA-SM still elicits 60% to 80% of at-level muscle
      spindle response. CONCLUSION: Intervertebral fixation decreases paraspinal muscle
      spindle response during L6 HVLA-SM in a cat model. Whereas HVLA-SM target
      accuracy maximizes spindle response, nontarget HVLA-SM still elicits substantial
      levels of muscle spindle activity. LEVEL OF EVIDENCE: N/A.

PMID- 25856265
TI  - Consequences of inducing intrinsic disorder in a high-affinity protein-protein
      interaction.
AB  - The kinetic and thermodynamic consequences of intrinsic disorder in protein
      protein recognition are controversial. We address this by inducing one partner of
      the high-affinity colicin E3 rRNase domain-Im3 complex (K(d) ~ 10(-12) M) to
      become an intrinsically disordered protein (IDP). Through a variety of
      biophysical measurements, we show that a single alanine mutation at Tyr507 within
      the hydrophobic core of the isolated colicin E3 rRNase domain causes the enzyme
      to become an IDP (E3 rRNase(IDP)). E3 rRNase(IDP) binds stoichiometrically to Im3
      and forms a structure that is essentially identical to the wild-type complex.
      However, binding of E3 rRNase(IDP) to Im3 is 4 orders of magnitude weaker than
      that of the folded rRNase, with thermodynamic parameters reflecting the disorder
      to-order transition on forming the complex. Critically, pre-steady-state kinetic
      analysis of the E3 rRNase(IDP)-Im3 complex demonstrates that the decrease in
      affinity is mostly accounted for by a drop in the electrostatically steered
      association rate. Our study shows that, notwithstanding the advantages intrinsic
      disorder brings to biological systems, this can come at severe kinetic and
      thermodynamic cost.

PMID- 25856266
TI  - Spinal cord injury combined with felony history: effect on supported employment
      for Veterans.
AB  - In this secondary analysis of data from a randomized controlled trial comparing
      supported employment with treatment as usual, we sought to evaluate the study
      incident rate of legal involvement and subsequent effects of legal involvement on
      employment among 157 job-seeking Veterans with spinal cord injury. The supported
      employment vocational rehabilitation program, called the Spinal Cord Injury
      Vocational Integration Program, adhered as closely as possible to principles of
      supported employment as developed and described in the individual placement and
      support model of supported employment for persons with mental illness. Rates of
      misdemeanor and felony arrests and convictions were analyzed, and their
      relationship to finding employment was evaluated. Findings indicate that 47% had
      been arrested and 25% had been convicted of a felony. Overall, those who found
      employment had fewer average arrests and were significantly less likely to have
      been convicted of a felony. Future directions and limitations are discussed.
      CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; NCT00117806.

PMID- 25856267
TI  - Paroxysmal nocturnal hemoglobinuria: pathogenesis, testing, and diagnosis.

PMID- 25856268
TI  - Hemoglobinuria: the role of the hematopathologist.

PMID- 25856269
TI  - Pulmonary Embolism Response to Fragmentation, Embolectomy, and Catheter
      Thrombolysis (PERFECT): Initial Results From a Prospective Multicenter Registry.
AB  - BACKGROUND: Systemic thrombolysis for acute pulmonary embolism (PE) carries up to
      a 20% risk of major bleeding, including a 2% to 5% risk of hemorrhagic stroke. We
      evaluated the safety and effectiveness of catheter-directed therapy (CDT) as an
      alternative treatment of acute PE. METHODS: One hundred one consecutive patients
      receiving CDT for acute PE were prospectively enrolled in a multicenter registry.
      Massive PE (n = 28) and submassive PE (n = 73) were treated with immediate
      catheter-directed mechanical or pharmacomechanical thrombectomy and/or catheter
      directed thrombolysis through low-dose hourly drug infusion with tissue
      plasminogen activator (tPA) or urokinase. Clinical success was defined as meeting
      all the following criteria: stabilization of hemodynamics; improvement in
      pulmonary hypertension, right-sided heart strain, or both; and survival to
      hospital discharge. Primary safety outcomes were major procedure-related
      complications and major bleeding events. RESULTS: Fifty-three men and 48 women
      (average age, 60 years [range, 22-86 years]; mean BMI, 31.03 +/- 7.20 kg/m2) were
      included in the study. The average thrombolytic doses were 28.0 +/- 11 mg tPA (n
      = 76) and 2,697,101 +/- 936,287 International Units for urokinase (n = 23).
      Clinical success was achieved in 24 of 28 patients with massive PE (85.7%; 95%
      CI, 67.3%-96.0%) and 71 of 73 patients with submassive PE (97.3%; 95% CI, 90.5%
      99.7%). The mean pulmonary artery pressure improved from 51.17 +/- 14.06 to 37.23
      +/- 15.81 mm Hg (n = 92) (P < .0001). Among patients monitored with follow-up
      echocardiography, 57 of 64 (89.1%; 95% CI, 78.8%-95.5%; P < .0001) showed
      improvement in right-sided heart strain. There were no major procedure-related
      complications, major hemorrhages, or hemorrhagic strokes. CONCLUSIONS: CDT
      improves clinical outcomes in patients with acute PE while minimizing the risk of
      major bleeding. At experienced centers, CDT is a safe and effective treatment of
      both acute massive and submassive PE. TRIAL REGISTRY: ClinicalTrials.gov; No.:
      NCT01097928; URL: www.clinicaltrials.gov.

PMID- 25856270
TI  - The "physician on call patient engagement trial" (POPET): measuring the impact of
      a mobile patient engagement application on health outcomes and quality of life in
      allergic rhinitis and asthma patients.
AB  - BACKGROUND: In this prospective, multicenter, randomized, controlled, double
      blind study, we investigated the impact of a mobile patient engagement
      application on health outcomes and quality of life in allergic rhinitis (AR) and
      asthma patients. METHODS: In total, 327 patients with diagnoses of persistent AR
      or mild-to-severe persistent asthma were randomized into 2 intervention groups
      and 2 control groups upon their admission at outpatient clinics. The intervention
      groups (POPET-AR and POPET-Asthma) received a mobile phone application
      ("physician on call patient engagement trial" [POPET]), enabling them to
      communicate with their physician, and record their health status and medication
      compliance. The AR groups completed the Rhinitis Quality of Life Questionnaire
      (RQLQ) at initiation and at the first month of the study. The asthma groups
      completed the Asthma Control Test (ACT) at initiation and at the third month of
      the study. RESULTS: The POPET-AR group showed better clinical improvement than
      the control group in terms of the overall RQLQ score as well in measures of
      general problems, activity, symptoms other than nose/eye, and emotion domains (p
      < 0.05). In the POPET-Asthma group, more patients (49%) achieved a well
      controlled asthma score (ACT > 19) compared with the control group (27%); this
      was statistically significant (p < 0.05). CONCLUSION: Use of a mobile engagement
      platform, such as POPET, can have a significant impact on health outcomes and
      quality of life in both AR and asthma, potentially decreasing the number of
      hospital admissions, repeat doctor visits, and losses in productivity.
      Improvements were seen in domains related to activity, productivity, perception
      of disease, and emotion.

PMID- 25856271
TI  - Distinct Metal Isoforms Underlie Promiscuous Activity Profiles of Metalloenzymes.
AB  - Within a superfamily, functionally diverged metalloenzymes often favor different
      metals as cofactors for catalysis. One hypothesis is that incorporation of
      alternative metals expands the catalytic repertoire of metalloenzymes and
      provides evolutionary springboards toward new catalytic functions. However, there
      is little experimental evidence that incorporation of alternative metals changes
      the activity profile of metalloenzymes. Here, we systematically investigate how
      metals alter the activity profiles of five functionally diverged enzymes of the
      metallo-beta-lactamase (MBL) superfamily. Each enzyme was reconstituted in vitro
      with six different metals, Cd(2+), Co(2+), Fe(2+), Mn(2+), Ni(2+), and Zn(2+),
      and assayed against eight catalytically distinct hydrolytic reactions
      (representing native functions of MBL enzymes). We reveal that each enzyme metal
      isoform has a significantly different activity level for native and promiscuous
      reactions. Moreover, metal preferences for native versus promiscuous activities
      are not correlated and, in some cases, are mutually exclusive; only particular
      metal isoforms disclose cryptic promiscuous activities but often at the expense
      of the native activity. For example, the L1 B3 beta-lactamase displays a 1000
      fold catalytic preference for Zn(2+) over Ni(2+) for its native activity but
      exhibits promiscuous thioester, phosphodiester, phosphotriester, and lactonase
      activity only with Ni(2+). Furthermore, we find that the five MBL enzymes exist
      as an ensemble of various metal isoforms in vivo, and this heterogeneity results
      in an expanded activity profile compared to a single metal isoform. Our study
      suggests that promiscuous activities of metalloenzymes can stem from an ensemble
      of metal isoforms in the cell, which could facilitate the functional divergence
      of metalloenzymes.

PMID- 25856273
TI  - Reasons for non-adherence to nicotine patch therapy during the first month of a
      quit attempt.
AB  - INTRODUCTION: Prior research has shown that the transdermal nicotine patch is a
      safe and effective aid to smoking cessation, but adherence to the directed use of
      the nicotine patch is often low. Few studies have examined participant-reported
      reasons for non-adherence to nicotine patch therapy during a quit attempt. AIMS:
      The aim of this study was to evaluate adherence to nicotine patch therapy and to
      identify participant-reported reasons for non-adherence. METHODS: Participants
      were 201 current daily smokers who were offered 6-weekly group treatment sessions
      and were asked to report nicotine patch use and barriers to use. RESULTS: Seventy
      one (35.3%) participants were adherent for the first 28 days of treatment and 130
      (64.7%) participants were non-adherent. Commonly reported reasons for non
      adherence were forgetting to put the patch on (30%), not liking the experienced
      side effects (15%), resuming smoking (10%) and difficulty affording the cost of
      the patches (7%). CONCLUSIONS: Participant- reported barriers to adherence of
      nicotine patch therapy can be mitigated with advice from healthcare providers.
      Some examples of advice to patients could include carrying an extra patch, using
      community resources to obtain free or reduced cost nicotine patches, reviewing
      the effectiveness of nicotine replacement, and explaining side effects associated
      with the use of the nicotine patch.

PMID- 25856272
TI  - Difference in microRNA expression and editing profile of lung tissues from
      different pig breeds related to immune responses to HP-PRRSV.
AB  - Porcine reproductive and respiratory syndrome (PRRS) is one of the most
      devastating diseases for the pig industry. Our goal was to identify microRNAs
      involved in the host immune response to PRRS. We generated microRNA expression
      profiles of lung tissues from Tongcheng or Landrace pigs infected with a highly
      pathogenic PRRS virus (PRRSV) at 3, 5, 7 dpi (day post infection) and control
      individuals from these two breeds. Our data showed that 278 known and 294 novel
      microRNAs were expressed in these combined microRNA transcriptomes. Compared with
      control individuals, almost half of the known microRNAs (116 in Tongcheng and 153
      in Landrace) showed significantly differential expression (DEmiRNAs) at least
      once. The numbers of down-regulated DEmiRNAs were larger than the corresponding
      number of up-regulated DEmiRNAs in both breeds. Interestingly, miR-2320-5p, which
      was predicted to bind to conserved sequences of the PRRSV genome, was down
      regulated significantly at 3 dpi after PRRSV infection in both breeds. In
      addition, PRRSV infection induced a significant increase of microRNA editing
      level in both breeds. Our results provide novel insight into the role of microRNA
      in response to PRRSV infection in vivo, which will aid the research for
      developing novel therapies against PRRSV. 

PMID- 25856274
TI  - Pulled elbow in children: a case series including 66 patients.
AB  - The aim of this case series was to assess the data of 66 children (mean age 28
      months) with a diagnosis of pulled elbow. The most common time interval of injury
      was 12-6 p.m. and spring was the peak season. Children younger than 2 years of
      age had a higher rate of atypical injury history. A successful reduction by
      supination and flexion maneuver was achieved at the first attempt in 57 of 66
      patients. The patients admitted to the hospital within the first 2 h following
      the injury had a higher rate of successful reduction at the first attempt. The
      rate of radiographic examination was considerably high and a well-defined
      algorithm to avoid the complicacy in ordering a plain radiograph in such cases
      was suggested. All patients achieved full clinical recovery after a mean follow
      up of 2 years, and recurrence was observed in 16 of 66 children. 

PMID- 25856275
TI  - Prospective comparison of subtalar arthroereisis with lateral column lengthening
      for painful flatfeet.
AB  - We prospectively compared subtalar arthroereisis with lateral column calcaneal
      lengthening for the treatment of painful flatfeet. Twenty-four feet (mean age of
      patients 12.8 years) were treated. Kinematic motion analysis, pedobarometry, and
      radiography were performed, and the Oxford Ankle-Foot Questionnaire for Children
      was administered for each patient before surgery and at the 1-year follow-up. We
      found statistically significant improvements in both groups, with no difference
      in their outcomes. Both groups showed significantly improved hindfoot and midfoot
      motion and positioning. Hindfoot range of motion was preserved. Radiography and
      pedobarometry also revealed significant improvements. Subtalar arthroereisis is a
      valid and potentially less-invasive alternative to lateral column lengthening
      that merits further investigation. 

PMID- 25856276
TI  - Peroneal spastic flatfoot in adolescents with accessory talar facet impingement:
      a preliminary report.
AB  - This study analyzed imaging, arthroscopic findings, and treatment responses for
      peroneal spastic flatfoot (PSFF) caused by talocalcaneal impingement at the
      accessory anterolateral talar facet (AALTF) (accessory talar facet impingement)
      in 13 adolescents without histories of trauma and tarsal coalition. The AALTF was
      determined with computed tomography and MRI. Focal abutting bone marrow edema
      (FABME) on MRI around the AALTF was confirmed. In seven patients who underwent
      AALTF resection, subtalar arthroscopy was performed. All experienced alleviation
      PSFF after treatment; reduction in FABME was observed. AALTF resection alone is
      beneficial for PSFF caused by accessory talar facet impingement when peroneal
      spasms are restored by an injection of local anesthesia. 

PMID- 25856277
TI  - Does the GMFCS level influence the improvement in knee range of motion after
      rectus femoris transfer in cerebral palsy?
AB  - The aim of this study was to evaluate the influence of the Gross Motor Function
      Classification System (GMFCS) on the outcomes of rectus femoris transfer (RFT)
      for patients with cerebral palsy and stiff knee gait. We performed a
      retrospective review of patients seen at our gait laboratory from 1996 to 2013.
      Inclusion criteria were (i) spastic diplegic cerebral palsy, (ii) GMFCS levels I
      III, (iii) reduced peak knee flexion in swing (PKFSw<55 degrees ), and (iv)
      patients who underwent orthopedic surgery with preoperative and postoperative
      gait analysis. Patients were divided into two groups according to whether they
      received a concurrent RFT or not at the time of surgery: non-RFT group (185
      knees) and RFT group (123 knees). The primary outcome was the overall knee range
      of motion (KROM) derived from gait kinematics. The secondary outcomes were the
      PKFSw and the time of peak knee flexion in swing (tPKFSw). We observed a
      statistically significant improvement in KROM only for patients in the RFT group
      (P<0.001). However, PKFSw and tPKFSw improved in both groups after surgery
      (P<0.001 for all analyses). In the RFT group, the improvement in KROM was
      observed only for patients classified as GMFCS levels I and II. In the non-RFT
      group, no improvement in KROM was observed in any GMFCS level. In this study,
      patients at GMFCS levels I and II were more likely to benefit from the RFT
      procedure. 

PMID- 25856278
TI  - Potential barriers to randomized clinical trials in infants with brachial plexus
      birth palsy.
AB  - Randomized clinical trials (RCTs) are the gold standard for comparing medical
      treatments. However, pediatric surgical RCTs are uncommon. We sought the opinions
      of parents whose children had undergone reconstructive nerve surgery on
      participating in research studies. Twenty-nine of 30 parents indicated that they
      would enroll their child in a research study, and 24 of them indicated that they
      would enroll their child in a surgical RCT. However, the most common reason for
      willingness to participate was a desire to help their child, demonstrating a
      fundamental misunderstanding of RCTs. The burden is on the researcher to
      ascertain the subject's level of understanding before consenting to
      randomization. 

PMID- 25856279
TI  - Treatment of avulsion fractures of the intercondylar eminence by medial
      parapatellar approach, open reduction and cross wire fixation.
AB  - Avulsion fractures of the intercondylar eminence in children and adolescents are
      relatively uncommon and can lead to significant disability with improper union.
      Many operative techniques have been developed to fixate these fractures, most of
      them utilizing sophisticated fixation modes. In this study, a small medial
      parapatellar approach was used with open reduction and percutaneous cross
      Kirschner wire fixation. The aim of this study was to evaluate the effectiveness
      of this method. From 2007 to 2012, eight children were treated, mean age 11.8
      years (range 10-14 years). All underwent open reduction by a medial parapatellar
      incision and fixation by two cross Kirschner wires introduced in an oblique
      crossed manner from the medial and lateral aspects of the proximal tibia.
      Fractures were classified as Meyers and McKeever type III and were not candidates
      for conservative treatment. All operated limbs were immobilized postoperatively
      in a circular cast in extension for 6 weeks and allowed partial weight bearing
      from day 1 after the procedure. Outcomes were evaluated clinically and through
      radiographs taken during follow-up. All fractures were successfully reduced and
      healed, with no occurrences of malunion or nonunion. At follow-up, all patients
      had full knee range of motion, there was no gross laxity of the knee compared
      with the contralateral knee, and good functional outcome was achieved. On the
      basis of our experience, we believe that the procedure that we used is a simple,
      low-tech, and minimally invasive technique for the treatment of these fractures,
      with good functional outcome. 

PMID- 25856280
TI  - Synergy at work: evidence development and assessment of the business value of
      investments in workforce health.

PMID- 25856281
TI  - Effect of facial rejuvenation surgery on perceived attractiveness, femininity,
      and personality.
AB  - IMPORTANCE: To date, the conversation about facial rejuvenation surgery has
      focused on one goal: youthfulness. However, human beings are judged throughout
      life based on many other characteristics and personal qualities conveyed by their
      faces. The term facial profiling has been used to describe this act of
      determining personality attributes through visual observation. OBJECTIVES: To
      introduce the concept of facial profiling to the surgical literature and to
      evaluate and quantify the changes in personality perception that occur with
      facial rejuvenation surgery. DESIGN, SETTING, AND PARTICIPANTS: This study was a
      retrospective evaluation of preoperative and postoperative photographs of 30
      white female patients who underwent facial rejuvenation surgery between January
      1, 2009, and December 31, 2013. Procedures included rhytidectomy (face-lift),
      upper blepharoplasty, lower blepharoplasty, eyebrow-lift, neck-lift, and/or chin
      implant. The 60 photographs (30 preoperative and 30 postoperative) of these
      patients were split into 6 groups, each with 5 preoperative and 5 postoperative
      photographs. The same patient's preoperative and postoperative photographs were
      not included in any single group to avoid any recall bias. At least 24
      individuals rated each photograph for 6 personality traits (aggressiveness,
      extroversion, likeability, trustworthiness, risk seeking, and social skills), as
      well as for attractiveness and femininity. The raters were blinded as to the
      intent of the study. MAIN OUTCOMES AND MEASURES: Ratings of personality traits,
      attractiveness, and femininity. RESULTS: Of the 8 traits that were evaluated,
      analysis revealed 4 traits with statistically significant improvements when
      comparing preoperative and postoperative scores: likeability (+0.36, P < .01),
      social skills (+0.38, P = .01), attractiveness (+0.36, P = .01), and femininity
      (+0.39, P = .02). Improvement in scores for perceived trustworthiness (+0.22, P =
      .06), aggressiveness (-0.14, P = .32), extroversion (+0.19, P = .14), and risk
      seeking (+0.10, P = .27) did not demonstrate statistically significant changes.
      CONCLUSIONS AND RELEVANCE: Facial plastic surgery changes the perception of
      patients by those around them. Traditionally, these interventions have focused on
      improvements in youthful appearance, but this study illuminates the other
      dimensions of a patient's facial profile that are influenced by facial
      rejuvenation surgery. The data in this sample population demonstrate an increase
      in the perception of likeability, social skills, attractiveness, and femininity.
      To our knowledge, this is the first study in the surgical literature to evaluate
      these broader outcome measures after facial rejuvenation surgery. LEVEL OF
      EVIDENCE: NA.

PMID- 25856282
TI  - Autophagy stimulation abrogates herpes simplex virus-1 infection.
AB  - Herpes simplex virus-1 (HSV-1) is a double-stranded DNA virus that causes life
      long infections. HSV-1 infections may lead to herpetic stromal keratitis that may
      advance to corneal blindness. HSV-1 infections can also cause fatal conditions,
      such as herpes encephalitis, or neonatal disease. A major virulence mechanism of
      HSV-1 is the control of autophagy, an innate immune defense strategy that could
      otherwise degrade viral particles. Here, to investigate a new mechanism for
      antiviral therapy, we tested the effect of various autophagy inducers
      (physiological and pharmacological) on infection. Autophagy stimulation was
      confirmed to significantly suppress HSV-1 infection in various cell types,
      without affecting cell viability. This study establishes the importance of
      autophagy for regulating HSV-1 infection, and provides a proof-of-principle
      evidence for a novel antiviral mechanism. 

PMID- 25856283
TI  - Immunocontraception for managing feral cattle in Hong Kong.
AB  - Conflicts between human interests and feral cattle in Hong Kong derive from
      growing numbers of free-roaming cattle. Public antipathy towards lethal
      population control led the local authorities to consider fertility control to
      reduce cattle numbers. This study assessed the potential side effects of the
      immunocontraceptive GonaCon on individual female cattle and established the
      effectiveness of GonaCon to induce infertility. We evaluated GonaCon in 34
      captive cattle assigned to four groups: Control administered a sham solution;
      Webbed (surgically sterilized through removal of the oviducts), administered one
      dose of GonaCon; Webbed, administered one dose of GonaCon and a booster dose
      three months later, and Treated, administered one dose of GonaCon. The side
      effects of GonaCon were assessed by monitoring injection site, body weight, body
      condition, size of lymph nodes, body temperature, and feeding behaviour 1 week
      and 1, 3, 6, 9 and 12 months after vaccination and by haematological and
      biochemical variables at vaccination and three months post-vaccination. The
      effectiveness of GonaCon to cause infertility was monitored by quantifying anti
      GnRH antibody titres and by using kits to detect cycling and pregnancy. GonaCon
      treated cattle showed no injection site reaction, limping, or abnormal behaviour.
      No differences were observed in all physiological and welfare indicators between
      control and vaccinated cattle. All control cattle and 4 of the 12 cattle in the
      Treated group became pregnant. Cattle administered a booster dose had higher anti
      GnRH antibody titres than cattle that received one dose. We concluded that
      GonaCon does not compromise the animals' welfare and is effective in reducing
      fertility in cattle. A booster dose is likely to increase the duration of
      infertility. Further studies are required to assess the feasibility and costs of
      immunocontraception for controlling free-roaming cattle populations. 

PMID- 25856284
TI  - Highlights in lymphoma from the 2013 American Society of Hematology Annual
      Meeting and Exposition.

PMID- 25856285
TI  - Highlights in lymphoma from the 2013 American Society of Hematology Annual
      Meeting and Exposition: commentary.

PMID- 25856286
TI  - Erbium resurfacing: "a weaker option"?

PMID- 25856287
TI  - Repair of alar defects using a nasolabial flap and a partial-thickness cartilage
      complex graft.

PMID- 25856288
TI  - "Super u"--a technique for the treatment of ingrown nail.

PMID- 25856289
TI  - Laser (check)lists, licensing, and learning log.

PMID- 25856290
TI  - Electronic and Spectroscopic Properties of Avobenzone Derivatives Attached to Mo2
      Quadruple Bonds: Suppression of the Photochemical Enol-to-Keto Transformation.
AB  - From the reactions between Mo2(T(i)PB)4, where T(i)PB is 2,4,6
      triisopropylbenzoate, and 2 equiv of the acids 4-formylbenzoic acid, HBzald; 4-(3
      oxo-3-phenylpropanoyl)benzoic acid, HAvo; and 4-(2,2-difluoro-6-phenyl-2H
      1lambda(3),3,2lambda(4)-dioxaborinin-4-yl)benzoic acid, HAvoBF2, the compounds
      Mo2(T(i)PB)2(Bzald)2, I; Mo2(T(i)PB)2(Avo)2, II; and Mo2(T(i)PB)2(AvoBF2)2, III,
      have been isolated. Compounds I and II are red, and compound III is blue. The new
      compounds have been characterized by (1)H NMR, MALDI-TOF MS, steady-state
      absorption and emission spectroscopies, and femtosecond and nanosecond time
      resolved transient absorption and infrared spectroscopies. Electronic structure
      calculations employing density functional theory and time-dependent density
      functional theory have been carried out to aid in the interpretation of these
      data. These compounds have strong metal-to-ligand charge transfer, MLCT, and
      transitions in the visible region of their spectra, and these comprise the S1
      states having lifetimes ~5-15 ps. The triplet states are Mo2deltadelta* with
      lifetimes in the microseconds. The spectroscopic properties of I and II are
      similar, whereas the planarity of the ligand in III greatly lowers the energy of
      the MLCT and enhances the intensity of the time-resolved spectra. The Mo2 unit
      shifts the ground state equilibrium entirely to the enol form and quenches the
      degradation pathways of the avobenzone moiety. 

PMID- 25856291
TI  - Xenon Treatment Protects against Remote Lung Injury after Kidney Transplantation
      in Rats.
AB  - BACKGROUND: Ischemia-reperfusion injury (IRI) of renal grafts may cause remote
      organ injury including lungs. The authors aimed to evaluate the protective effect
      of xenon exposure against remote lung injury due to renal graft IRI in a rat
      renal transplantation model. METHODS: For in vitro studies, human lung epithelial
      cell A549 was challenged with H2O2, tumor necrosis factor-alpha, or conditioned
      medium from human kidney proximal tubular cells (HK-2) after hypothermia-hypoxia
      insults. For in vivo studies, the Lewis renal graft was stored in 4 degrees C
      Soltran preserving solution for 24 h and transplanted into the Lewis recipient,
      and the lungs were harvested 24 h after grafting. Cultured lung cells or the
      recipient after engraftment was exposed to 70% Xe or N2. Phospho (p)-mammalian
      target of rapamycin (mTOR), hypoxia-inducible factor-1alpha (HIF-1alpha), Bcl-2,
      high-mobility group protein-1 (HMGB-1), TLR-4, and nuclear factor kappaB (NF
      kappaB) expression, lung inflammation, and cell injuries were assessed. RESULTS:
      Recipients receiving ischemic renal grafts developed pulmonary injury. Xenon
      treatment enhanced HIF-1alpha, which attenuated HMGB-1 translocation and NF
      kappaB activation in A549 cells with oxidative and inflammatory stress. Xenon
      treatment enhanced p-mTOR, HIF-1alpha, and Bcl-2 expression and, in turn,
      promoted cell proliferation in the lung. Upon grafting, HMGB-1 translocation from
      lung epithelial nuclei was reduced; the TLR-4/NF-kappaB pathway was suppressed by
      xenon treatment; and subsequent tissue injury score (nitrogen vs. xenon: 26 +/-
      1.8 vs. 10.7 +/- 2.6; n = 6) was significantly reduced. CONCLUSION: Xenon
      treatment confers protection against distant lung injury triggered by renal graft
      IRI, which is likely through the activation of mTOR-HIF-1alpha pathway and
      suppression of the HMGB-1 translocation from nuclei to cytoplasm.

PMID- 25856292
TI  - Reversal of neuromuscular blockade: "identification friend or foe".

PMID- 25856293
TI  - Spatial heterogeneity regulates plant-pollinator networks across multiple
      landscape scales.
AB  - Mutualistic plant-pollinator interactions play a key role in biodiversity
      conservation and ecosystem functioning. In a community, the combination of these
      interactions can generate emergent properties, e.g., robustness and resilience to
      disturbances such as fluctuations in populations and extinctions. Given that
      these systems are hierarchical and complex, environmental changes must have
      multiple levels of influence. In addition, changes in habitat quality and in the
      landscape structure are important threats to plants, pollinators and their
      interactions. However, despite the importance of these phenomena for the
      understanding of biological systems, as well as for conservation and management
      strategies, few studies have empirically evaluated these effects at the network
      level. Therefore, the objective of this study was to investigate the influence of
      local conditions and landscape structure at multiple scales on the
      characteristics of plant-pollinator networks. This study was conducted in agri
      natural lands in Chapada Diamantina, Bahia, Brazil. Pollinators were collected in
      27 sampling units distributed orthogonally along a gradient of proportion of
      agriculture and landscape diversity. The Akaike information criterion was used to
      select models that best fit the metrics for network characteristics, comparing
      four hypotheses represented by a set of a priori candidate models with specific
      combinations of the proportion of agriculture, the average shape of the landscape
      elements, the diversity of the landscape and the structure of local vegetation.
      The results indicate that a reduction of habitat quality and landscape
      heterogeneity can cause species loss and decrease of networks nestedness. These
      structural changes can reduce robustness and resilience of plant-pollinator
      networks what compromises the reproductive success of plants, the maintenance of
      biodiversity and the pollination service stability. We also discuss the possible
      explanations for these relationships and the implications for landscape planning
      in agricultural areas. 

PMID- 25856294
TI  - The Harbin Cohort Study on Diet, Nutrition and Chronic Non-communicable Diseases:
      study design and baseline characteristics.
AB  - Diet and nutrition have been reported to be associated with many common chronic
      diseases and blood-based assessment would be vital to investigate the association
      and mechanism, however, blood-based prospective studies are limited. The Harbin
      Cohort Study on Diet, Nutrition and Chronic Non-communicable Diseases was set up
      in 2010. From 2010 to 2012, 9,734 participants completed the baseline survey,
      including demographic characteristics, dietary intake, lifestyles and physical
      condition, and anthropometrics. A re-survey on 490 randomly selected participants
      was done by using the same methods which were employed in the baseline survey.
      For all participants, the mean age was 50 years and 36% of them were men.
      Approximately 99.4 % of cohort members donated blood samples. The mean total
      energy intake was 2671.7 kcal/day in men and 2245.9 kcal/day in women, the mean
      body mass index was 25.7 kg/m2 in men and 24.6 kg/m2 in women, with 18.4% being
      obese (>= 28 kg/m2), 12.7% being diabetic, and 29.5% being hypertensive. A good
      agreement was obtained for the physical measurements between the baseline survey
      and re-survey. The resources from the cohort and its fasting and postprandial
      blood samples collected both at baseline and in each follow-up will be valuable
      and powerful in investigating relationship between diet, nutrition and chronic
      diseases and discovering novel blood biomarkers and the metabolism of these
      biomarkers related to chronic diseases.

PMID- 25856295
TI  - Structural and photoluminescence properties of stannate based displaced
      pyrochlore-type red phosphors: Ca(3-x)Sn3Nb2O14:xEu3+.
AB  - New stannate based displaced pyrochlore-type red phosphors, Ca(3
      x)Sn3Nb2O14:xEu(3+), were prepared via a conventional solid state method. The
      influence of partial occupancy of Sn in both A and B sites of the pyrochlore-type
      oxides on the photoluminescence properties was studied using powder X-ray
      diffraction, FT-Raman, transmission electron microscopy, scanning electron
      microscopy with energy dispersive spectrometry, UV-visible absorption
      spectroscopy, and photoluminescence excitation and emission spectra with lifetime
      measurements. The structural analysis establishes that these oxides belong to a
      cubic displaced pyrochlore type structure with a space group Fd3m. These
      phosphors exhibit strong absorptions at near UV and blue wavelength regions and
      emit intense multiband emissions due to Eu(3+ 5)D0-(7)F(0, 1, 2) transitions. The
      absence of characteristic MD transition splitting points out that local cation
      disorder exists in this type of displaced pyrochlores, reducing the D(3d)
      inversion symmetry, which is not evidenced by such disorder in the X-ray
      diffraction analysis. The unusual forbidden intense sharp (5)D0-(7)F0 transition
      indicates single site occupancy of Eu(3+) with a narrower range of bonding
      environment, preventing the cluster formation. This is supported by the stable
      (5)D0 lifetime with Eu(3+) concentration. The Judd-Ofelt intensity parameter
      assessment corroborates these results. The CIE color coordinates of these
      phosphors were found to be (0.60, 0.40), which are close to the NTSC standard
      values (0.67, 0.33) for a potential red phosphor.

PMID- 25856296
TI  - Statistical and prognostic analysis of dynamic changes of platelet count in ICU
      patients.
AB  - Laboratory tests are a primary resource to diagnose patient's diseases. However,
      physicians often make decisions based on the available information, which
      commonly includes the last test results as a static picture and have limited
      perspective of the role of trends in commonly measured parameters in enhancing
      the diagnostic process. By providing a dynamic patient profile the diagnosis
      could be more accurate and, as a consequence, physicians could anticipate changes
      in recovery trajectory and prescribe interventions more effectively. Intensive
      care unit (ICU) patients need continuous monitoring, which commonly includes the
      assessment of several blood components. One of these components is the platelet
      count which is used in assessing blood clotting. However, platelet counts
      represent a dynamic equilibrium of many simultaneous processes including altered
      capillary permeability, inflammatory cascades, as well as the coagulation
      process. To characterize the value of dynamic changes in platelet counts we
      applied analytic methods to datasets of critically ill patients in (i) a
      homogeneous population of ICU cardiac surgery patients, where an observation
      appears to be predictive of patient's complications and mortality and (ii) a
      heterogeneous group of ICU patients to confirm the previous observation. 

PMID- 25856297
TI  - MiRNA-615-5p functions as a tumor suppressor in pancreatic ductal adenocarcinoma
      by targeting AKT2.
AB  - BACKGROUND: Aberrant microRNA (miRNA) expression is associated with tumor
      development. This study aimed to elucidate the role of miR-615-5p in the
      development of pancreatic ductal adenocarcinoma (PDAC). METHODS: Locked nucleic
      acid in situ hybridization (LNA-ISH) was performed to compare miR-615-5p
      expression in patients between PDAC and matched adjacent normal tissues. Effects
      of miR-615-5p overexpression on cell proliferation, apoptosis, colony formation,
      migration, and invasion were determined in the pancreatic cancer cell lines PANC
      1 and MIA PaCa-2. Effects of miR-615-5p on AKT2 were examined by dual-luciferase
      reporter assay. Lentivirus expressing miR-615 was used to create stable
      overexpression cell lines, which were subsequently used in mouse xenograft and
      metastasis models to assess tumor growth, apoptosis and metastasis. RESULTS: miR
      615-5p expression was significantly lower in PDAC than in adjacent normal
      tissues. Low levels of miR-615-5p were independently associated with poor
      prognosis (HR: 2.243, 95% CI: 1.190-4.227, P=0.013). AKT2 protein expression was
      inversely correlated with miR-615-5p expression (r=-0.3, P=0.003). miR-615-5p
      directly targeted the 3'-untranslated region of AKT2 mRNA and repressed its
      expression. miR-615-5p overexpression inhibited pancreatic cancer cell
      proliferation, migration, and invasion in vitro, and tumor growth and metastasis
      in vivo. Furthermore, miR-615-5p overexpression also induced pancreatic cancer
      cell apoptosis both in vitro and in vivo. CONCLUSIONS: These results show that
      miR-615-5p inhibits pancreatic cancer cell proliferation, migration, and invasion
      by targeting AKT2. The data implicate miR-615-5p in the prognosis and treatment
      of PDAC.

PMID- 25856298
TI  - Effects of tibolone and its metabolites on prolactin and insulin-like growth
      factor binding protein-1 expression in human endometrial stromal cells.
AB  - The effects of the postmenopausal replacement steroid tibolone and its 3alpha-,
      3beta-OH and Delta-4 tibolone metabolites were evaluated on progesterone receptor
      mediated classic decidualization markers insulin-like growth factor binding
      protein-1 (IGFBP-1) and prolactin expression in human endometrial stromal cells
      (HESCs). Supernatants of conditioned medium or erxtracted RNA from experimental
      cell incubations of confluent HESCs were subjected to ELISAs, Western blot
      analysis and RT/PCR, and results were statisically assesed. Over 21 days,
      specific ELISAs observed linear increases in secreted IGFBP-1 and prolactin
      levels elicited by tibolone and its metabolites. Cultured HESCs were refractory
      to E2 and dexamethasone, whereas tibolone and each metabolite exceeded
      medroxyprogesterone acetate in significantly elevating IGFBP-1 and prolactin
      output. Anti-progestins eliminated IGFBP-1 and prolactin induction by tibolone
      and its metabolites. Immunoblotting and RT/PCR confirmed ELISA results. These
      observations of IGFBP-1 and prolactin expression: (a) indicate the relevance of
      cultured HESCs in evaluating the chronic effects of tibolone administration to
      women; (b) are consistent with PR-mediated endometrial atrophy and protection
      against endometrial bleeding despite the persistence of circulating ER-binding,
      but not PR-binding metabolites following tibolone administration to women.

PMID- 25856299
TI  - Obesity adversely impacts the number and maturity of oocytes in conventional IVF
      not in minimal stimulation IVF.
AB  - OBJECTIVE: The objective of this study was to assess the relationship between BMI
      and oocyte number and maturity in participants who underwent minimal stimulation
      (mini-) or conventional IVF. METHODS: Participants who underwent their first
      autologous cycle of either conventional (n = 219) or mini-IVF (n = 220) were
      divided according to their BMI to analyze IVF outcome parameters. The main
      outcome measure was the number of oocytes in metaphase II (MII). Secondary
      outcomes included the number of total oocytes retrieved, fertilized (2PN)
      oocytes, cleavage and blastocyst stage embryos, clinical pregnancy (CP), and live
      birth (LB) rates. RESULTS: In conventional IVF, but not in mini-IVF, the number
      of total oocytes retrieved (14.5  +/-  0.8 versus 8.8  +/-  1.3) and MII oocytes
      (11.2 +/- 0.7 versus 7.1 +/- 1.1) were significantly lower in obese compared with
      normal BMI women. Multivariable linear regression adjusting for age, day 3 FSH,
      days of stimulation, and total gonadotropin dose demonstrated that BMI was an
      independent predictor of the number of MII oocytes in conventional IVF (p =
      0.0004). Additionally, only in conventional IVF, BMI was negatively correlated
      with the total number of 2PN oocytes, as well as the number of cleavage stage
      embryos. CONCLUSIONS: Female adiposity might impair oocyte number and maturity in
      conventional IVF but not in mini-IVF. These data suggest that mild ovarian
      stimulation might yield healthier oocytes in obese women.

PMID- 25856300
TI  - A genomic safe haven for mutant complementation in Cryptococcus neoformans.
AB  - Just as Koch's postulates formed the foundation of early infectious disease
      study, Stanley Falkow's molecular Koch's postulates define best practice in
      determining whether a specific gene contributes to virulence of a pathogen.
      Fundamentally, these molecular postulates state that if a gene is involved in
      virulence, its removal will compromise virulence. Likewise, its reintroduction
      should restore virulence to the mutant. These approaches are widely employed in
      Cryptococcus neoformans, where gene deletion via biolistic transformation is a
      well-established technique. However, the complementation of these mutants is less
      straightforward. Currently, one of three approaches will be taken: the gene is
      reintroduced at the original locus, the gene is reintroduced into a random site
      in the genome, or the mutant is not complemented at all. Depending on which
      approach is utilized, the mutant may be complemented but other genes are
      potentially disrupted in the process. To counter the drawbacks of the current
      approaches to complementation we have created a new tool to assist in this key
      step in the study of a gene's role in virulence. We have identified and
      characterized a small gene-free region in the C. neoformans genome dubbed the
      "safe haven", and constructed a plasmid vector that targets DNA constructs to
      this preselected site. The plasmid vector integrates with high frequency,
      effectively complementing a mutant strain without disrupting adjacent genes. qRT
      PCR of the flanking genes on either side of the safe haven site following
      integration of the targeting vector revealed no changes in their expression, and
      no secondary phenotypes were observed in a range of phenotypic assays including
      an intranasal murine infection model. Combined, these data confirm that we have
      successfully created a much-needed molecular resource for the Cryptococcus
      community, enabling the reliable fulfillment of the molecular Koch's postulates. 

PMID- 25856302
TI  - Co-delivery of doxorubicin and siRNA for glioma therapy by a brain targeting
      system: angiopep-2-modified poly(lactic-co-glycolic acid) nanoparticles.
AB  - It is very challenging to treat brain cancer because of the blood-brain barrier
      (BBB) restricting therapeutic drug or gene to access the brain. In this research
      project, angiopep-2 (ANG) was used as a brain-targeted peptide for preparing
      multifunctional ANG-modified poly(lactic-co-glycolic acid) (PLGA) nanoparticles
      (NPs), which encapsulated both doxorubicin (DOX) and epidermal growth factor
      receptor (EGFR) siRNA, designated as ANG/PLGA/DOX/siRNA. This system could
      efficiently deliver DOX and siRNA into U87MG cells leading to significant cell
      inhibition, apoptosis and EGFR silencing in vitro. It demonstrated that this drug
      system was capable of penetrating the BBB in vivo, resulting in more drugs
      accumulation in the brain. The animal study using the brain orthotopic U87MG
      glioma xenograft model indicated that the ANG-targeted co-delivery of DOX and
      EGFR siRNA resulted in not only the prolongation of the life span of the glioma
      bearing mice but also an obvious cell apoptosis in glioma tissue. 

PMID- 25856301
TI  - Development of a new model system to dissect isoform specific Akt signalling in
      adipocytes.
AB  - Protein kinase B (Akt) kinases are critical signal transducers mediating insulin
      action. Genetic studies revealed that Akt1 and Akt2 signalling differentially
      contribute to sustain lipid and glucose homoeostasis; however Akt isoform
      specific effectors remain elusive due to the lack of a suitable model system to
      mechanistically interrogate Akt isoform-specific signalling. To overcome those
      technical limitations we developed a novel model system that provides acute and
      specific control of signalling by Akt isoforms. We generated mutants of Akt1 and
      Akt2 resistant to the allosteric Akt inhibitor MK-2206. We then developed
      adipocyte cell lines, in which endogenous Akt1 or Akt2 has been replaced by their
      corresponding drug-resistant Akt mutant. Treatment of those cells with MK-2206
      allowed for acute and specific control of either Akt1 or Akt2 function. Our data
      showed that Akt1(W80A) and Akt2(W80A) mutants are resistant to MK-2206,
      dynamically regulated by insulin and able to signal to Akt downstream effectors.
      Analyses of insulin action in this cellular system showed that Akt1 and Akt2 are
      both able to mediate insulin regulation of the transcription factor forkhead box
      O1 (FoxO1) and the glucose transporter 4 (GLUT4), revealing a redundant role for
      these Akt kinases in the control of glucose transport into fat cells. In
      contrast, Akt1 signalling is uniquely required for adipogenesis, by controlling
      the mitotic clonal expansion (MCE) of pre-adipocytes that precedes white adipose
      cell differentiation. Our data provide new insights into the role of Akt kinases
      in glucose transport and adipogenesis and support our model system as a valuable
      tool for the biochemical characterization of signalling by specific Akt isoforms.

PMID- 25856303
TI  - Structural modeling of a novel CAPN5 mutation that causes uveitis and neovascular
      retinal detachment.
AB  - CAPN5 mutations have been linked to autosomal dominant neovascular inflammatory
      vitreoretinopathy (ADNIV), a blinding autoimmune eye disease. Here, we link a new
      CAPN5 mutation to ADNIV and model the three-dimensional structure of the
      resulting mutant protein. In our study, a kindred with inflammatory
      vitreoretinopathy was evaluated by clinical eye examinations, DNA sequencing, and
      protein structural modeling to investigate the disease-causing mutation. Two
      daughters of an affected mother demonstrated symptoms of stage III ADNIV, with
      posterior uveitis, cystoid macular edema, intraocular fibrosis, retinal
      neovascularization, retinal degeneration, and cataract. The women also harbored a
      novel guanine to thymine (c.750G>T, p.Lys250Asn) missense mutation in exon 6 of
      CAPN5, a gene that encodes a calcium-activated cysteine protease, calpain-5.
      Modeling based on the structures of all known calpains revealed the mutation
      falls within a calcium-sensitive flexible gating loop that controls access to the
      catalytic groove. Three-dimensional modeling placed the new mutation in a region
      adjacent to two previously identified disease-causing mutations, all three of
      which likely disrupt hydrogen bonding within the gating loop, yielding a CAPN5
      with altered enzymatic activity. This is the third case of a CAPN5 mutation
      leading to inherited uveitis and neovascular vitreoretinopathy, suggesting
      patients with ADNIV features should be tested for CAPN5 mutations. Structural
      modeling of novel variants can be used to support mechanistic consequences of the
      disease-causing variants. 

PMID- 25856305
TI  - Production of limit size nanoliposomal systems with potential utility as ultra
      small drug delivery agents.
AB  - Previous studies from this group have shown that limit size lipid-based systems-
      defined as the smallest achievable aggregates compatible with the packing
      properties of their molecular constituents--can be efficiently produced using
      rapid microfluidic mixing technique. In this work, it is shown that similar
      procedures can be employed for the production of homogeneously sized unilamellar
      vesicular systems of 30-40 nm size range. These vesicles can be remotely loaded
      with the protonable drug doxorubicin and exhibit adequate drug retention
      properties in vitro and in vivo. In particular, it is demonstrated that whereas
      sub-40 nm lipid nanoparticle (LNP) systems consisting entirely of long-chain
      saturated phosphatidylcholines cannot be produced, the presence of such lipids
      may have a beneficial effect on the retention properties of limit size systems
      consisting of mixed lipid components. Specifically, a 33-nm diameter doxorubicin
      loaded LNP system composed of 1-palmitoyl-2-oleoyl phosphatidylcholine (POPC),
      1,2-dipalmitoyl phosphatidylcholine (DPPC), cholesterol, and PEGylated lipid
      (DSPE-PEG2000) demonstrated adequate, stable drug retention in the circulation,
      with a half-life for drug release of ~ 12 h. These results indicate that
      microfluidic mixing is the technique of choice for the production of bilayer LNP
      systems with sizes less than 50 nm that could lead to development of a novel
      class of ultra-small drug delivery vehicles.

PMID- 25856304
TI  - Drug repurposing: a systematic approach to evaluate candidate oral
      neuroprotective interventions for secondary progressive multiple sclerosis.
AB  - OBJECTIVE: To develop and implement an evidence based framework to select, from
      drugs already licenced, candidate oral neuroprotective drugs to be tested in
      secondary progressive multiple sclerosis. DESIGN: Systematic review of clinical
      studies of oral putative neuroprotective therapies in MS and four other
      neurodegenerative diseases with shared pathological features, followed by
      systematic review and meta-analyses of the in vivo experimental data for those
      interventions. We presented summary data to an international multi-disciplinary
      committee, which assessed each drug in turn using pre-specified criteria
      including consideration of mechanism of action. RESULTS: We identified a short
      list of fifty-two candidate interventions. After review of all clinical and pre
      clinical evidence we identified ibudilast, riluzole, amiloride, pirfenidone,
      fluoxetine, oxcarbazepine, and the polyunsaturated fatty-acid class (Linoleic
      Acid, Lipoic acid; Omega-3 fatty acid, Max EPA oil) as lead candidates for
      clinical evaluation. CONCLUSIONS: We demonstrate a standardised and systematic
      approach to candidate identification for drug rescue and repurposing trials that
      can be applied widely to neurodegenerative disorders.

PMID- 25856306
TI  - Optimized multi-site local orbitals in the large-scale DFT program CONQUEST.
AB  - We introduce numerical optimization of multi-site support functions in the linear
      scaling DFT code CONQUEST. Multi-site support functions, which are linear
      combinations of pseudo-atomic orbitals on a target atom and those neighbours
      within a cutoff, have been recently proposed to reduce the number of support
      functions to the minimal basis while keeping the accuracy of a large basis [J.
      Chem. Theory Comput., 2014, 10, 4813]. The coefficients were determined by using
      the local filter diagonalization (LFD) method [Phys. Rev. B: Condens. Matter
      Mater. Phys., 2009, 80, 205104]. We analyse the effect of numerical optimization
      of the coefficients produced by the LFD method. Tests on crystalline silicon, a
      benzene molecule and hydrated DNA systems show that the optimization improves the
      accuracy of the multi-site support functions with small cutoffs. It is also
      confirmed that the optimization guarantees the variational energy minimizations
      with multi-site support functions. 

PMID- 25856307
TI  - Melting glacier impacts community structure of Bacteria, Archaea and Fungi in a
      Chilean Patagonia fjord.
AB  - Jorge Montt glacier, located in the Patagonian Ice Fields, has undergone an
      unprecedented retreat during the past century. To study the impact of the
      meltwater discharge on the microbial community of the downstream fjord, we
      targeted Bacteria, Archaea and Fungi communities during austral autumn and
      winter. Our results showed a singular microbial community present in cold and low
      salinity surface waters during autumn, when a thicker meltwater layer was
      observed. Meltwater bacterial sequences were related to Cyanobacteria,
      Proteobacteria, Actinobacteria and Bacteriodetes previously identified in
      freshwater and cold ecosystems, suggesting the occurrence of microorganisms
      adapted to live in the extreme conditions of meltwater. For Fungi, representative
      sequences related to terrestrial and airborne fungal taxa indicated transport of
      allochthonous Fungi by the meltwater discharge. In contrast, bottom fjord waters
      from autumn and winter showed representative Operational Taxonomic Units (OTUs)
      related to sequences of marine microorganisms, which is consistent with current
      models of fjord circulation. We conclude that meltwater can significantly modify
      the structure of microbial communities and support the development of a major
      fraction of microorganisms in surface waters of Patagonian fjords. 

PMID- 25856309
TI  - Photochemical aging of secondary organic aerosols generated from the
      photooxidation of polycyclic aromatic hydrocarbons in the gas-phase.
AB  - Aging processes of secondary organic aerosol (SOA) may be a source of oxygenated
      organic aerosols; however, the chemical processes involved remain unclear. In
      this study, we investigate photochemical aging of SOA produced by the gas-phase
      oxidation of naphthalene by hydroxyl radicals and acenaphthylene by ozone. We
      monitored the SOA composition using a high-resolution time-of-flight aerosol mass
      spectrometer. We initiated SOA aging with UV photolysis alone and with OH
      radicals in the presence or absence of light and at different NOx levels. For
      naphthalene, the organic composition of the particulate phase seems to be
      dominated by highly oxidized compounds such as carboxylic acids, and aging data
      may be consistent with diffusion limitations. For acenaphthylene, the fate of
      oxidized products and the moderately oxidized aerosol seem to indicate that
      functionalization reactions might be the main aging process were initiated by the
      cumulative effect of light and OH radicals. 

PMID- 25856308
TI  - Heterologous prime-boost regimens with a recombinant chimpanzee adenoviral vector
      and adjuvanted F4 protein elicit polyfunctional HIV-1-specific T-Cell responses
      in macaques.
AB  - HIV-1-specific CD4+ and CD8+ T lymphocytes are important for HIV-1 replication
      control. F4/AS01 consists of F4 recombinant fusion protein (containing clade B
      Gag/p24, Pol/RT, Nef and Gag/p17) formulated in AS01 Adjuvant System, and was
      shown to induce F4-specific polyfunctional CD4+ T-cell responses in humans. While
      replication-incompetent recombinant HIV-1/SIV antigen-expressing human adenoviral
      vectors can elicit high-frequency antigen-specific CD8+ T-cell responses, their
      use is hampered by widespread pre-existing immunity to human serotypes. Non-human
      adenovirus serotypes associated with lower prevalence may offer an alternative
      strategy. We evaluated the immunogenicity of AdC7-GRN ('A'), a recombinant
      chimpanzee adenovirus type 7 vector expressing clade B Gag, RT and Nef, and
      F4/AS01 ('P'), when delivered intramuscularly in homologous (PP or AA) and
      heterologous (AAPP or PPAA) prime-boost regimens, in macaques and mice. Vaccine
      induced HIV-1-antigen-specific T cells in peripheral blood (macaques), liver,
      spleen, and intestinal and genital mucosa (mice) were characterized by
      intracellular cytokine staining. Vaccine-specific IgG antibodies (macaques) were
      detected using ELISA. In macaques, only the heterologous prime-boost regimens
      induced polyfunctional, persistent and balanced CD4+ and CD8+ T-cell responses
      specific to each HIV-1 vaccine antigen. AdC7-GRN priming increased the
      polyfunctionality of F4/AS01-induced CD4+ T cells. Approximately 50% of AdC7-GRN
      induced memory CD8+ T cells exhibited an effector-memory phenotype. HIV-1
      specific antibodies were detected with each regimen. In mice, antigen-specific
      CD4+ and CD8+ T-cell responses were detected in the mucosal and systemic
      anatomical compartments assessed. When administered in heterologous prime-boost
      regimens, AdC7-GRN and F4/AS01 candidate vaccines acted complementarily in
      inducing potent and persistent peripheral blood HIV-1-specific CD4+ and CD8+ T
      cell responses and antibodies in macaques. Besides, adenoviral vector priming
      modulated the cytokine-expression profile of the protein-induced CD4+ T cells.
      Each regimen induced HIV-1-specific T-cell responses in systemic/local tissues in
      mice. This suggests that prime-boost regimens combining adjuvanted protein and
      low-seroprevalent chimpanzee adenoviral vectors represent an attractive
      vaccination strategy for clinical evaluation. 

PMID- 25856310
TI  - Correction: Ly49E expression on CD8alphaalpha-expressing intestinal
      intraepithelial lymphocytes plays no detectable role in the development and
      progression of experimentally induced inflammatory bowel diseases.

PMID- 25856311
TI  - Age-related onset of obesity corresponds with metabolic dysregulation and altered
      microglia morphology in mice deficient for Ifitm proteins.
AB  - The IfitmDel mouse lacks all five of the Ifitm genes via LoxP deletion. This
      animal breeds normally with no obvious defect in development. The IfitmDel
      animals exhibit a steady and significantly enhanced weight gain relative to wild
      type controls beginning about three months of age and under normal feeding
      conditions. The increased weight corresponds with elevated fat mass, and in
      tolerance tests they are hyporesponsive to insulin but respond normally to
      glucose. Both young (4 mo) and older (12 mo) IfitmDel mice have enhanced levels
      of serum leptin suggesting a defect in leptin/leptin receptor signaling. Analysis
      of the gene expression profiles in the hypothalamus of IfitmDel animals, compared
      to WT, demonstrated an altered ratio of Pomc and Npy neuropeptide expression,
      which likely impairs the satiation response of the IfitmDel animal leading to an
      increased eating behavior. Also elevated in hypothalamus of IfitmDel mice were
      pro-inflammatory cytokine expression and reduced IL-10. Anatomical analysis of
      the hypothalamus using immunohistochemistry revealed that microglia exhibit an
      abnormal morphology in IfitmDel animals and respond abnormally to Poly:IC
      challenge. These abnormalities extend the phenotype of the IfitmDel mouse beyond
      abnormal responses to viral challenge to include a metabolic phenotype and weight
      gain. Further, this novel phenotype for the IfitmDel mouse could be related to
      abnormal neuropeptide production, inflammatory status and microglia status in the
      hypothalamus. 

PMID- 25856312
TI  - O-fucosylation of DLL3 is required for its function during somitogenesis.
AB  - Delta-like 3 (DLL3) is a member of the DSL family of Notch ligands in amniotes.
      In contrast to DLL1 and DLL4, the other Delta-like proteins in the mouse, DLL3
      does not bind in trans to Notch and does not activate the receptor, but shows cis
      interaction and cis-inhibitory properties on Notch signaling in vitro. Loss of
      the DSL protein DLL3 in the mouse results in severe somite patterning defects,
      which are virtually indistinguishable from the defects in mice that lack lunatic
      fringe (LFNG), a glycosyltransferase involved in modifying Notch signaling. Like
      LFNG, DLL3 is located within the trans-Golgi, however, its biochemical function
      is still unclear. Here, we show that i) both proteins interact, ii) epidermal
      growth factor like repeats 2 and 5 of DLL3 are O-fucosylated at consensus sites
      for POFUT1, and iii) further modified by FNG proteins in vitro. Embryos double
      homozygous for null mutations in Dll3 and Lfng are phenotypically
      indistinguishable from the single mutants supporting a potential common function.
      Mutation of the O-fucosylation sites in DLL3 does not disrupt the interaction of
      DLL3 with LFNG or full length Notch1or DLL1, and O-fucosylation-deficient DLL3
      can still inhibit Notch in cis in vitro. However, in contrast to wild type DLL3,
      O-fucosylation-deficient DLL3 cannot compensate for the loss of endogenous DLL3
      during somitogenesis in the embryo. Together our results suggest that the cis
      inhibitory activity of DLL3 observed in cultured cells might not fully reflect
      its assumed essential physiological property, suggest that DLL3 and LFNG act
      together, and strongly supports that modification of DLL3 by O-linked fucose is
      essential for its function during somitogenesis. 

PMID- 25856314
TI  - Altered plasma lysophosphatidylcholines and amides in non-obese and non-diabetic
      subjects with borderline-to-moderate hypertriglyceridemia: a case-control study.
AB  - Hypertriglyceridemia (HTG) is a risk factor for atherosclerotic cardiovascular
      disease (CVD). We investigated alterations in plasma metabolites associated with
      borderline-to-moderate HTG (triglycerides (TG) 150-500 mg/dL). Using UPLC-LTQ
      Orbitrap mass spectrometry analysis, the metabolomics profiles of 111 non
      diabetic and non-obese individuals with borderline-to-moderate HTG were compared
      with those of 111 age- and sex-matched controls with normotriglyceridemia (NTG,
      TG <150 mg/dL). When compared to the NTG control group, the HTG group exhibited
      higher plasma levels of lysophosphatidylcholines (lysoPCs), including C14:0 (q =
      0.001) and C16:0 (q = 1.8E-05), and several amides, including N-ethyldodecanamide
      (q = 2.9E-05), N-propyldodecanamide (q = 3.5E-05), palmitoleamide (q = 2.9E-06),
      and palmitic amide (q = 0.019). The metabolomic profiles of the HTG group also
      exhibited lower plasma levels of cis-4-octenedioic acid (q<1.0E-9) and
      docosanamide (q = 0.002) compared with those of the NTG controls. LysoPC 16:0 and
      palmitoleamide emerged as the primary metabolites able to discriminate the HTG
      group from the NTG group in a partial least-squares discriminant analysis and
      were positively associated with the fasting triglyceride levels. We identified
      alterations in lysoPCs, amides, and cis-4-octenedioic acid among non-diabetic and
      non-obese individuals with borderline-to-moderate HTG. These results provide
      novel insights into the metabolic alterations that occur in the early metabolic
      stages of HTG. This information may facilitate the design of early interventions
      to prevent disease progression. 

PMID- 25856313
TI  - Bioinformatic identification and expression analysis of banana microRNAs and
      their targets.
AB  - MicroRNAs (miRNAs) represent a class of endogenous non-coding small RNAs that
      play important roles in multiple biological processes by degrading targeted mRNAs
      or repressing mRNA translation. Thousands of miRNAs have been identified in many
      plant species, whereas only a limited number of miRNAs have been predicted in M.
      acuminata (A genome) and M. balbisiana (B genome). Here, previously known plant
      miRNAs were BLASTed against the Expressed Sequence Tag (EST) and Genomic Survey
      Sequence (GSS), a database of banana genes. A total of 32 potential miRNAs
      belonging to 13 miRNAs families were detected using a range of filtering
      criteria. 244 miRNA:target pairs were subsequently predicted, most of which
      encode transcription factors or enzymes that participate in the regulation of
      development, growth, metabolism, and other physiological processes. In order to
      validate the predicted miRNAs and the mutual relationship between miRNAs and
      their target genes, qRT-PCR was applied to detect the tissue-specific expression
      levels of 12 putative miRNAs and 6 target genes in roots, leaves, flowers, and
      fruits. This study provides some important information about banana pre-miRNAs,
      mature miRNAs, and miRNA target genes and these findings can be applied to future
      research of miRNA functions. 

PMID- 25856315
TI  - Development and validation of a risk score for predicting death after
      pneumonectomy.
AB  - Pneumonectomy is associated with significant postoperative mortality. This study
      was undertaken to develop and validate a risk model of mortality following
      pneumonectomy. We reviewed our prospective database and identified 774
      pneumonectomies from a total of 7792 consecutive anatomical lung resections in
      the years 2003 to 2010 (rate of pneumonectomy: 9.9%). Based on data from 542
      pneumonectomies between 2003 and 2007 (i.e., the "discovery set"), a penalized
      multivariable logistic regression analysis was performed to identify preoperative
      risk factors. A risk model was developed and validated in an independent data set
      of 232 pneumonectomies that were performed between 2008 and 2010 (i.e., the
      "validation set"). Of the 542 patients in the discovery set (DS), 35 patients
      (6.5%) died after pneumonectomy during the same admission. We developed a risk
      prediction model for in-hospital mortality following pneumonectomy; that model
      included age, current alcohol use, coronary artery disease, preoperative
      leukocyte count and palliative indication as possible risk factors. The risk
      model was subsequently successfully validated in an independent data set (n =
      232) in which 18 patients (7.8%) died following pneumonectomy. For the validation
      set, the sensitivity of the model was 53.3% (DS: 54.3%), the specificity was
      88.0% (DS: 87.4%), the positive predictive value was 26.7% (DS: 22.9%) and the
      negative predictive value was 95.8% (DS: 96.5%). The Brier score was 0.062 (DS:
      0.054). The prediction model is statistically valid and clinically relevant. 

PMID- 25856317
TI  - Correction: A single molecule investigation of the photostability of quantum
      dots.

PMID- 25856316
TI  - Prognostic value, clinicopathologic features and diagnostic accuracy of
      interleukin-8 in colorectal cancer: a meta-analysis.
AB  - BACKGROUND: The prognostic value and diagnostic accuracy of Interleukin-8 (IL-8)
      in colorectal cancer have been assessed with several studies, but the conclusions
      were inconclusive. Thus we performed a meta-analysis to evaluate the impact of IL
      8 expression on colorectal cancer prognosis, clinicopathologic features and
      diagnostic accuracy. METHODS: Comprehensive search strategies were used to search
      relevant literature in the PubMed, EBSCO and the ISI Web of Science databases.
      The correlation between IL-8 expression and prognosis, clinicopathologic features
      and diagnostic accuracy was analyzed. RESULTS: A total of 18 articles met the
      inclusion criteria, including 1509 patients for clinicopathologic features or
      prognosis evaluation and 725 participants for diagnostic evaluation. The results
      suggested that overexpression of IL-8 was significantly associated with poor
      prognosis in colorectal cancer (HR = 1.54, 95%CI 1.03-2.32), especially in Union
      for International Cancer Control (UICC) stage IV patients (HR = 2.28, 95%CI 1.60
      3.25). With further subgroup analysis, we found that high IL-8 level in serum was
      significantly correlated with poor prognosis (HR = 2.13, 95%CI 1.49-3.05). In
      addition, significant correlations were observed between high IL-8 expression and
      advanced stage (OR = 3.01, 95%CI 1.98-4.56), lymphatic metastasis (OR = 2.24,
      95%CI 1.39-3.63), and liver metastasis (OR = 3.47, 95%CI 1.74-6.89). Moreover, IL
      8 had high diagnostic accuracy, with pooled sensitivity 0.70(95%CI 0.66-0.74),
      specificity 0.91(95%CI 0.86-0.94), positive likelihood ratio (LR) 7.00(95%CI 2.48
      19.73), negative LR 0.24(95%CI 0.09-0.64), diagnostic OR 24.00(95%CI 5.52
      104.38). CONCLUSIONS: This study showed that IL-8 could be a potential indicator
      for detecting colorectal cancer and predicting prognosis. In addition, high IL-8
      level was significantly correlated with advanced stage, lymphatic metastasis,
      liver metastasis.

PMID- 25856318
TI  - Paula Pitha-Rowe, PhD (1938-2015).

PMID- 25856319
TI  - Long-term retrospective follow-up of turned and moderately rough implants in the
      edentulous jaw.
AB  - AIM: To compare the long-term clinical outcome of turned vs. moderately rough
      implants. MATERIALS AND METHODS: Patients treated with implants in the edentulous
      mandible and/or maxilla were invited for a clinical examination. After prosthesis
      removal, the pocket depth was measured and the bleeding scored. Also, a new
      radiograph was taken for bone loss evaluation. Patients were also requested to
      rate their satisfaction with the treatment. RESULTS: One hundred and ninety-seven
      implants in 33 patients were evaluated. After a mean follow-up of 172 months (SD
      42, range 120-252), the mean loss was 1.61 mm (SD 1.35, range 0.00-8.25). Bone
      loss was higher in the maxilla compared to the mandible (P < 0.001), and at
      implants, that was restored on implant level (P = 0.003). Multivariate analyses
      demonstrated a significant effect of implant surface roughness and time of
      loading on bone loss. Smoking, on the other hand, did not affect the outcome.
      Mean pocket probing depth was 3.64 mm (SD 0.96, range 1.25-7.25). A total of 4.1%
      of the implants demonstrated signs of peri-implantitis. The overall patient
      satisfaction rate was 98.5%. CONCLUSION: Implant treatment in the edentulous jaw
      has a predictable long-term outcome with limited complications.

PMID- 25856320
TI  - A comprehensive review of plants and their active constituents with wound healing
      activity in traditional Iranian medicine.
AB  - INTRODUCTION: Wound healing is a complex cascade of events with various cellular
      and biochemical processes that result in reconstruction and regeneration of
      damaged tissue. The objective of the current study was to scientifically evaluate
      the medicinal plants said to produce wound healing activity in traditional
      Iranian medicine (TIM). MATERIAL AND METHODS: Electronic databases were searched
      for the names of medicinal plants claimed in TIM literature for having wound
      healing activity. Articles were evaluated to obtain any in vitro, animal, or
      clinical evidence of their efficacy and possible mechanisms involved in would
      healing. RESULTS: Mechanisms of action for some of these plants, including
      Tamarix spp., Rosa spp., Piper betle, Plantago major, Oxalis spp., Olea europaea,
      Malva spp., Linum usitatissimum, and Tamarindus indica, have not been yet
      clarified. In contrast, some herbs such as Vitis vinifera, Quercus spp., Punica
      granatum, Pinus spp., Polygonum spp., Lilium spp., Gentiana lutea, Arnebia
      euchroma, Aloe spp., and Caesalpinia spp. have various biological and
      pharmacological mechanisms that have been verified for wound healing activity.
      CONCLUSIONS: Overall, TIM resources have introduced various medicinal plants for
      wounds with confirmed effectiveness according to current pharmacological studies.
      These herbal remedies could be considered as future drugs for healing of wounds.
      Further pharmacological and clinical investigations are recommended for exploring
      safety, exact mechanisms, and efficacy of these herbal remedies.    .

PMID- 25856321
TI  - Clinical utility of growth factors and platelet-rich plasma in tissue
      regeneration: a review.
AB  - INTRODUCTION: Many elements are involved in the regenerative processof injured
      tissues, such as cytokines and growth factors. Growth factors contained in
      platelets represent an important physiological mixture of factors that may be
      involved in the healing process. METHOD: A literature review on the role played
      by certain biomolecules, such as growth factors and platelet-rich plasma (PRP),
      in the healing of different tissues and on their therapeutic use to promote this
      process was undertaken. RESULTS: In this review, the authors found a great number
      of studies that showed the effect of growth factors and PRP in the regeneration
      of different tissues. Platelet-rich plasma is a natural source of growth factors
      and this has been successfully used in different clinical situations such as
      dentistry, plastic surgery, trauma and orthopedics, ocular surgery,
      gastroenterology, or skin ulcers. However, standardized protocol for its
      preparation and applicationhas yet to be established. CONCLUSION: The authors
      recommend further research is required to establish the exact role of PRP in the
      treatment of tissue regeneration and to develop a standardized protocol for its
      use.

PMID- 25856322
TI  - Burns induced by cupping therapy in a burn center in northeast china.
AB  - Cupping therapy as a curative skill has been developed and applied throughout
      history. Despite reports of adverse effects, this therapy is considered to be
      relatively safe with no systemic reviews documenting negative side effects. The
      aim of this study was to explore methods that avoid the adverse effects sometimes
      associated with this therapy. METHODS: Clinical records of 14 outpatients and
      inpatients that visited the First Hospital of Jilin University (Changchun, China)
      for management of burn injuries caused by cupping therapy were retrospectively
      reviewed. Characteristics, history of injury, and treatment of each patient was
      collected and analyzed. RESULTS: Burn injury induced by cupping therapy was not
      uncommon. Most of the injuries were mild to moderate and cured by conservative
      methods without severe complications. The use of wet cupping was more prevalent
      among injured patients than dry cupping. CONCLUSION: Cupping therapy as an
      ancient alternative treatment is still popular with a large number of devoted
      practitioners. Although there is the potential for injury during the application
      of this therapy, this is mostly preventable. Standardized training for health
      care professionals and increased the awareness among the public about the proper
      methods to administer this therapy to avoid adverse effects is important.

PMID- 25856324
TI  - Corroles-porphyrins: a teamwork for gas sensor arrays.
AB  - Porphyrins provide an excellent material for chemical sensors, and they have been
      used for sensing species both in air and solution. In the gas phase, the broad
      selectivity of porphyrins is largely dependant on molecular features, such as the
      metal ion complexed at the core of the aromatic ring and the peripheral
      substituents. Although these features have been largely exploited to design gas
      sensor arrays, so far, little attention has been devoted to modify the sensing
      properties of these macrocycles by variation of the molecular aromatic ring. In
      this paper, the gas sensing properties of a porphyrin analog, the corrole, are
      studied in comparison with those of the parent porphyrin. Results show that
      changes in the aromatic ring have important consequences on the sensitivity and
      selectivity of the sensors and that porphyrins and corroles can positively
      cooperate to enhance the performance of sensor arrays. 

PMID- 25856323
TI  - Beyond Yellow Curry: Assessing Commercial Curcumin Absorption Technologies.
AB  - BACKGROUND: Few natural products have demonstrated the range of protective and
      therapeutic promise as have turmeric and its principal bioactive components:
      curcumin, demethoxycurcumin, and bisdemethoxycurcumin. Success in translating
      this potential into tangible benefits has been limited by inherently poor
      intestinal absorption, rapid metabolism, and limited systemic bioavailability.
      Seeking to overcome these limitations, food ingredient formulators have begun to
      employ a variety of approaches to enhance absorption and bioactivity. Many of
      these strategies improve upon the age-old practice of consuming turmeric in fat
      based sauces, such as in a fat-rich yellow curry. However, there exists
      uncertainty as to how the various commercially available offerings compare to
      each other in terms of either uptake or efficacy, and this uncertainty leaves
      physicians and nutritionists with a dearth of data for making recommendations to
      interested patients and consumers. Further complicating the issue are recent data
      suggesting that formulation strategies may not equally enhance the absorption of
      individual curcuminoids, a significant issue in that these curcuminoids exhibit
      somewhat different physiologic properties. OBJECTIVE: This review introduces
      needed order to the curcumin marketplace by examining bioavailability studies on
      a number of commercial curcumin ingredients and evaluating them on a level
      playing field. METHODS: The comparative analysis includes standard
      pharmacokinetic parameters and a new metric, relative mass efficiency (E).
      Relative mass efficiency allows for the comparison of different formulations even
      in cases in which the weight percentage of curcuminoids is vastly different.
      RESULTS: A hydrophilic carrier dispersed curcuminoid formula exhibits 45.9 times
      the bioavailability of the standard purified 95 percent curcuminoid preparation
      and, based on relative mass efficiency, 1.5 times the bioavailability of the next
      best commercial ingredient, a cyclodextrin complex. CONCLUSIONS: Delivery
      strategies can significantly improve the bioavailability of curcuminoids. Total
      formula mass is important for making practical formulation decisions about
      dosing, cost and space.

PMID- 25856325
TI  - Decentralized system identification using stochastic subspace identification for
      wireless sensor networks.
AB  - Wireless sensor networks (WSNs) facilitate a new paradigm to structural
      identification and monitoring for civil infrastructure. Conventional structural
      monitoring systems based on wired sensors and centralized data acquisition
      systems are costly for installation as well as maintenance. WSNs have emerged as
      a technology that can overcome such difficulties, making deployment of a dense
      array of sensors on large civil structures both feasible and economical. However,
      as opposed to wired sensor networks in which centralized data acquisition and
      processing is common practice, WSNs require decentralized computing algorithms to
      reduce data transmission due to the limitation associated with wireless
      communication. In this paper, the stochastic subspace identification (SSI)
      technique is selected for system identification, and SSI-based decentralized
      system identification (SDSI) is proposed to be implemented in a WSN composed of
      Imote2 wireless sensors that measure acceleration. The SDSI is tightly scheduled
      in the hierarchical WSN, and its performance is experimentally verified in a
      laboratory test using a 5-story shear building model. 

PMID- 25856326
TI  - Light-addressable measurement of in vivo tissue oxygenation in an unanesthetized
      zebrafish embryo via phase-based phosphorescence lifetime detection.
AB  - We have developed a digital light modulation system that utilizes a modified
      commercial projector equipped with a laser diode as a light source for
      quantitative measurements of in vivo tissue oxygenation in an unanesthetized
      zebrafish embryo via phase-based phosphorescence lifetime detection. The oxygen
      sensitive phosphorescent probe (Oxyphor G4) was first inoculated into the
      bloodstream of 48 h post-fertilization (48 hpf) zebrafish embryos via the
      circulation valley to rapidly disperse probes throughout the embryo. The
      unanesthetized zebrafish embryo was introduced into the microfluidic device and
      immobilized on its lateral side by using a pneumatically actuated membrane. By
      controlling the illumination pattern on the digital micromirror device in the
      projector, the modulated excitation light can be spatially projected to
      illuminate arbitrarily-shaped regions of tissue of interest for in vivo oxygen
      measurements. We have successfully measured in vivo oxygen changes in the cardiac
      region and cardinal vein of a 48 hpf zebrafish embryo that experience hypoxia and
      subsequent normoxic conditions. Our proposed platform provides the potential for
      the real-time investigation of oxygen distribution in tissue microvasculature
      that relates to physiological stimulation and diseases in a developing organism. 

PMID- 25856327
TI  - Impact wave monitoring in soil using a dynamic fiber sensor based on stimulated
      brillouin scattering.
AB  - The impact wave response of soil due to a ball drop is monitored on a 30.5 cm by
      30.5 cm square soil box using a fiber sensor with dynamic strain sensing
      capability. The experiments are conducted in real time using a simple one-laser
      one-modulator configuration with stimulated Brillouin scattering. The embedded
      BOTDA sensor grid successfully monitored the distribution and evolution of the
      inner strains of a sand bed during a mass impact on its surface. The measurement
      of the distributed dynamic strains was possible in several milliseconds and with
      1 cm actual location resolution. This paper presents a time-domain signal
      analysis utilized for determining the dynamic strains in embedded fiber sensor.
      The results demonstrate the method to be a promising one for detection of
      subsurface vibration and movement in geotechnical Structure Health Monitoring
      (SHM). 

PMID- 25856328
TI  - Motion-blurred particle image restoration for on-line wear monitoring.
AB  - On-line images of wear debris contain important information for real-time
      condition monitoring, and a dynamic imaging technique can eliminate particle
      overlaps commonly found in static images, for instance, acquired using
      ferrography. However, dynamic wear debris images captured in a running machine
      are unavoidably blurred because the particles in lubricant are in motion. Hence,
      it is difficult to acquire reliable images of wear debris with an adequate
      resolution for particle feature extraction. In order to obtain sharp wear
      particle images, an image processing approach is proposed. Blurred particles were
      firstly separated from the static background by utilizing a background
      subtraction method. Second, the point spread function was estimated using power
      cepstrum to determine the blur direction and length. Then, the Wiener filter
      algorithm was adopted to perform image restoration to improve the image quality.
      Finally, experiments were conducted with a large number of dynamic particle
      images to validate the effectiveness of the proposed method and the performance
      of the approach was also evaluated. This study provides a new practical approach
      to acquire clear images for on-line wear monitoring. 

PMID- 25856329
TI  - Combining users' activity survey and simulators to evaluate human activity
      recognition systems.
AB  - Evaluating human activity recognition systems usually implies following expensive
      and time-consuming methodologies, where experiments with humans are run with the
      consequent ethical and legal issues. We propose a novel evaluation methodology to
      overcome the enumerated problems, which is based on surveys for users and a
      synthetic dataset generator tool. Surveys allow capturing how different users
      perform activities of daily living, while the synthetic dataset generator is used
      to create properly labelled activity datasets modelled with the information
      extracted from surveys. Important aspects, such as sensor noise, varying time
      lapses and user erratic behaviour, can also be simulated using the tool. The
      proposed methodology is shown to have very important advantages that allow
      researchers to carry out their work more efficiently. To evaluate the approach, a
      synthetic dataset generated following the proposed methodology is compared to a
      real dataset computing the similarity between sensor occurrence frequencies. It
      is concluded that the similarity between both datasets is more than significant. 

PMID- 25856330
TI  - Multi-model estimation based moving object detection for aerial video.
AB  - With the wide development of UAV (Unmanned Aerial Vehicle) technology, moving
      target detection for aerial video has become a popular research topic in the
      computer field. Most of the existing methods are under the registration-detection
      framework and can only deal with simple background scenes. They tend to go wrong
      in the complex multi background scenarios, such as viaducts, buildings and trees.
      In this paper, we break through the single background constraint and perceive the
      complex scene accurately by automatic estimation of multiple background models.
      First, we segment the scene into several color blocks and estimate the dense
      optical flow. Then, we calculate an affine transformation model for each block
      with large area and merge the consistent models. Finally, we calculate
      subordinate degree to multi-background models pixel to pixel for all small area
      blocks. Moving objects are segmented by means of energy optimization method
      solved via Graph Cuts. The extensive experimental results on public aerial videos
      show that, due to multi background models estimation, analyzing each pixel's
      subordinate relationship to multi models by energy minimization, our method can
      effectively remove buildings, trees and other false alarms and detect moving
      objects correctly. 

PMID- 25856331
TI  - A Kinect-based real-time compressive tracking prototype system for amphibious
      spherical robots.
AB  - A visual tracking system is essential as a basis for visual servoing, autonomous
      navigation, path planning, robot-human interaction and other robotic functions.
      To execute various tasks in diverse and ever-changing environments, a mobile
      robot requires high levels of robustness, precision, environmental adaptability
      and real-time performance of the visual tracking system. In keeping with the
      application characteristics of our amphibious spherical robot, which was proposed
      for flexible and economical underwater exploration in 2012, an improved RGB-D
      visual tracking algorithm is proposed and implemented. Given the limited power
      source and computational capabilities of mobile robots, compressive tracking
      (CT), which is the effective and efficient algorithm that was proposed in 2012,
      was selected as the basis of the proposed algorithm to process colour images. A
      Kalman filter with a second-order motion model was implemented to predict the
      state of the target and select candidate patches or samples for the CT tracker.
      In addition, a variance ratio features shift (VR-V) tracker with a Kalman
      estimation mechanism was used to process depth images. Using a feedback strategy,
      the depth tracking results were used to assist the CT tracker in updating
      classifier parameters at an adaptive rate. In this way, most of the deficiencies
      of CT, including drift and poor robustness to occlusion and high-speed target
      motion, were partly solved. To evaluate the proposed algorithm, a Microsoft
      Kinect sensor, which combines colour and infrared depth cameras, was adopted for
      use in a prototype of the robotic tracking system. The experimental results with
      various image sequences demonstrated the effectiveness, robustness and real-time
      performance of the tracking system. 

PMID- 25856332
TI  - Inhibitory effects of NAMI-A-like ruthenium complexes on prion neuropeptide
      fibril formation.
AB  - Prion diseases are a group of infectious and fatal neurodegenerative disorders
      caused by the conformational conversion of a cellular prion protein (PrP) into
      its abnormal isoform PrP(Sc). PrP106-126 resembles PrP(Sc) in terms of
      physicochemical and biological characteristics and is used as a common model for
      the treatment of prion diseases. Inhibitory effects on fibril formation and
      neurotoxicity of the prion neuropeptide PrP106-126 have been investigated using
      metal complexes as potential inhibitors. Nevertheless, the binding mechanism
      between metal complexes and the peptide remains unclear. The present study is
      focused on the interaction of PrP106-126 with NAMI-A and NAMI-A-like ruthenium
      complexes, including KP418, KP1019, and KP1019-2. Results demonstrated that these
      ruthenium complexes could bind to PrP106-126 in a distinctive binding mode
      through electrostatic and hydrophobic interactions. NAMI-A-like ruthenium
      complexes can also effectively inhibit the aggregation and fibril formation of
      PrP106-126. The complex KP1019 demonstrated the optimal inhibitory ability upon
      peptide aggregation, and cytotoxicity because of its large aromatic ligand
      contribution. The studied complexes could also regulate the copper redox
      chemistry of PrP106-126 and effectually inhibit the formation of reactive oxygen
      species. Given these findings, ruthenium complexes with relatively low cellular
      toxicity may be used to develop potential pharmaceutical products against prion
      diseases. 

PMID- 25856333
TI  - A Novel Combination Point-of-View (POV) Action Camera Recording to Capture the
      Surgical Field and Instrument Ergonomics in Oculoplastic Surgery.
AB  - PURPOSE: To evaluate a novel combination head-mounted/chest-mounted point-of-view
      recording system for oculoplastic surgical procedures. METHODS: The point-of-view
      head camera captures the surgical field, while the point-of-view chest camera
      captures a wide field of view to record instrument ergonomics. Various methods of
      recording were trialed. RESULTS: The head camera with a narrow field of view was
      better for recording fine details of the surgical field. The chest camera
      recording a wide field of view was optimal for recording hand positions.
      Stereoscopic recording of the instrument ergonomics was helpful in relaying the
      relative positions of the surgeon's hands and instruments. CONCLUSIONS: Point-of
      view cameras are cost-effective means of recording oculoplastics procedures. The
      authors feel simultaneously recording the surgeon's ergonomics and the
      corresponding instrument movements within the surgical field, from the "surgeon's
      view", will augment surgical education.

PMID- 25856334
TI  - Primary Transitional Cell Carcinoma of the Conjunctiva.
AB  - A 77-year-old male presented with a large papillomatous conjunctival lesion on
      his lower eyelid. Biopsy and extensive systemic investigation revealed this to be
      a primary conjunctival transitional cell carcinoma. Patient preference and
      coexisting medical problems dictated conservative management with surgical
      debulking, topical mitomicin, and radiotherapy. Local control has been maintained
      for 4 years to date.

PMID- 25856335
TI  - Vellus Hair Cyst of the Orbit.
AB  - Eruptive vellus hair cysts are a developmental abnormality of vellus hair
      follicles that result in small cystic papules occurring most frequently on the
      chest and proximal extremities. Lesions of the ocular adnexa are extremely rare,
      and to the best of the authors knowledge, involvement of the orbit has never been
      reported. The authors describe a patient with an eruptive vellus hair cyst
      involving the orbit.

PMID- 25856336
TI  - Dermis-Fat Graft in Children as Primary and Secondary Orbital Implant.
AB  - PURPOSE: To report the experience with the use of dermis-fat graft in the
      pediatric population and to evaluate the outcome of this procedure as a primary
      or secondary orbital implant. METHODS: Case series. Analysis of the clinical
      charts of 22 patients. Age at the time of surgery ranged from 2.1 to 13 years.
      Three patients affected were submitted to evisceration with primary dermis-fat
      graft. Six patients had explantation of exposed implants and a replacement with a
      dermis-fat graft. Three patients had a dermis-fat graft to repair contracted
      sockets. Ten patients were affected by congenital anophthalmia: 4 patients had a
      primary dermis-fat graft, 6 patients had a removal of a socket expander, or an
      orbital spherical expander, or pellet expanders and a replacement with a dermis
      fat graft. This study adheres to the principles outlined in the Declaration of
      Helsinki. RESULTS: The patients' follow up ranged between 2.5 and 8 years. Only 1
      child who had a primary dermis-fat graft experienced excessive growth of the
      implant, managed by surgical debulking. In the end, all the patients showed
      satisfactory orbital volume along with adequate fornices. CONCLUSIONS: The dermis
      fat graft as a primary implant may be useful in children with severe
      scleromalacia or following ocular trauma. It is a suitable option in children
      affected by congenital anophthalmia as it helps continued socket expansion. It
      can also be considered in the pediatric population to address the volume deficit
      following explantation of exposed implants and in contracted sockets.

PMID- 25856337
TI  - Pediatric Acute Dacryocystitis.
AB  - PURPOSE: To review and summarize the symptomatology, microbiology, special
      clinical entities, management, complications, and outcomes of pediatric acute
      dacryocystitis. METHODS: The author performed a PubMed search of all articles
      published in English on acute dacryocystitis. Pediatric subpopulations of these
      articles were reviewed along with the scant literature of direct references to
      neonatal and pediatric acute dacryocystitis. Data reviewed included demographics,
      presentations, microbiological work up, management, complications, and outcomes.
      RESULTS: Acute dacryocystitis is not very common in the pediatric age groups and
      occurs mostly as a complication of congenital nasolacrimal duct obstruction. The
      age of onset is usually in the neonatal period with a female preponderance. The
      clinical spectrum ranges from classic pediatric acute dacryocystitis to
      meningitis. Staphylococcus aureus is the commonest isolate. Occasionally acquired
      etiologies and rare organisms like Pantoea sp., Epstein-Barr Virus, and
      Sporothrix are implicated in the etiopathogenesis. The diagnosis is usually
      clinical aided by laboratory investigations. Better antibiotics, well-established
      laboratory techniques and surgical modalities, and improved patient care
      logistics have contributed to good outcomes; however, complications are still
      being noted although infrequently. CONCLUSIONS: Pediatric acute dacryocystitis is
      a distinct entity with unique features of its own. It is a serious infection that
      warrants careful evaluation and immediate management. In the era of antibiotic
      resistance, microbiological work up of Pediatric acute dacryocystitis is very
      useful for subsequent treatment. Surgical challenges in the pediatric age group
      are distinct and the outcomes are good if standard protocols are followed.

PMID- 25856339
TI  - Erratum.

PMID- 25856338
TI  - The relationship between mode of delivery and sexual health outcomes after
      childbirth.
AB  - INTRODUCTION: Several factors are implicated in the women's sexuality after
      childbirth. Nevertheless, there is conflicting evidence about the influence of
      mode of delivery (MD) AIM: To prospectively evaluate the relationship between MD
      and sexual health outcomes after childbirth METHODS: A prospective cohort study
      conducted between May 2005 and March 2007 included 831 pregnant women recruited
      from primary care clinics of the public sector in Sao Paulo, Brazil. The exposure
      variable was MD: uncomplicated vaginal delivery (spontaneous vaginal delivery
      without episiotomy or any kind of perineal laceration); complicated vaginal
      delivery (either forceps or normal, with episiotomy or any kind of perineal
      laceration) and cesarean delivery. Socio-demographic and obstetric data were
      obtained through a questionnaire applied during the antenatal and postnatal
      period. Crude and adjusted risk ratios, with 95% confidence intervals, were
      calculated using Poisson regression to examine the associations between MD and
      sexual health outcomes. MAIN OUTCOME MEASURES: The three main sexual health
      outcomes were later resumption of sexual life, self-perception of decline of
      sexual life (DSL), and presence of sexual desire. RESULTS: One hundred and forty
      one women (21.9%) resumed sexual life 3 or more months after delivery. Although
      87.1% of women had desire, DSL occurred in 21.1% of the cohort. No associations
      were found between MD and sexual health outcomes. CONCLUSIONS: Women's sexuality
      after childbirth were not influenced by the type of delivery. Efforts to improve
      the treatment of sexual problems after childbirth should focus beyond MD.

PMID- 25856340
TI  - Purification and characterization of a DNA-binding recombinant PREP1:PBX1
      complex.
AB  - Human PREP1 and PBX1 are homeodomain transcriptional factors, whose biochemical
      and structural characterization has not yet been fully described. Expression of
      full-length recombinant PREP1 (47.6 kDa) and PBX1 (46.6 kDa) in E. coli is
      difficult because of poor yield, high instability and insufficient purity, in
      particular for structural studies. We cloned the cDNA of both proteins into a
      dicistronic vector containing an N-terminal glutathione S-transferase (GST) tag
      and co-expressed and co-purified a stable PBX1:PREP1 complex. For structural
      studies, we produced two C-terminally truncated complexes that retain their
      ability to bind DNA and are more stable than the full-length proteins through
      various purification steps. Here we report the production of large amounts of
      soluble and pure recombinant human PBX1:PREP1 complex in an active form capable
      of binding DNA. 

PMID- 25856341
TI  - Clinical indicators for bacterial co-infection in Ghanaian children with P.
      falciparum infection.
AB  - Differentiation of infectious causes in severely ill children is essential but
      challenging in sub- Saharan Africa. The aim of the study was to determine
      clinical indicators that are able to identify bacterial co-infections in P.
      falciparum infected children in rural Ghana. In total, 1,915 severely ill
      children below the age of 15 years were recruited at Agogo Presbyterian Hospital
      in Ghana between May 2007 and February 2011. In 771 (40%) of the children malaria
      parasites were detected. This group was analyzed for indicators of bacterial co
      infections using bivariate and multivariate regression analyses with 24 socio
      economic variables, 16 terms describing medical history and anthropometrical
      information and 68 variables describing clinical symptoms. The variables were
      tested for sensitivity, specificity, positive predictive value and negative
      predictive value. In 46 (6.0%) of the children with malaria infection, bacterial
      co-infection was detected. The most frequent pathogens were non-typhoid
      salmonellae (45.7%), followed by Streptococcus spp. (13.0%). Coughing,
      dehydration, splenomegaly, severe anemia and leukocytosis were positively
      associated with bacteremia. Domestic hygiene and exclusive breastfeeding is
      negatively associated with bacteremia. In cases of high parasitemia
      (>10,000/MUl), a significant association with bacteremia was found for
      splenomegaly (OR 8.8; CI 1.6-48.9), dehydration (OR 18.2; CI 2.0-166.0) and
      coughing (OR 9.0; CI 0.7-118.6). In children with low parasitemia, associations
      with bacteremia were found for vomiting (OR 4.7; CI 1.4-15.8), severe anemia (OR
      3.3; CI 1.0-11.1) and leukocytosis (OR 6.8 CI 1.9-24.2). Clinical signs of
      impaired microcirculation were negatively associated with bacteremia. Ceftriaxone
      achieved best coverage of isolated pathogens. The results demonstrate the
      limitation of clinical symptoms to determine bacterial co-infections in P.
      falciparum infected children. Best clinical indicators are dependent on the
      parasitemia level. Even with a moderate sensitivity of >60%, only low positive
      predictive values can be obtained due to low prevalence of bacteremia. Rapid
      testing for distinguishing parasitemia and bacteremia is essential. 

PMID- 25856342
TI  - Case report: A retrospective serological analysis indicating human exposure to
      tick-borne relapsing fever spirochetes in Texas.

PMID- 25856343
TI  - T lymphocyte density and distribution in human colorectal mucosa, and
      inefficiency of current cell isolation protocols.
AB  - Mucosal tissues are critical immune effector sites containing complex populations
      of leukocytes in a tissue microenvironment that remains incompletely understood.
      We identify and quantify in human distal colorectal tissue absolute mucosal CD3+
      lymphocytes, including CD4+ and CD8+ subsets, by direct visualization using
      immunohistochemistry (IHC), immunofluorescence (IF), and an automated counting
      protocol (r2=0.90). Sigmoid and rectal mucosal tissues are both densely packed
      with T lymphocytes in the mucosal compartment. Both compartments had similar
      densities of CD3+ T lymphocytes with 37,400 +/- 2,801 cells/mm3 and 33,700 +/-
      4,324 cell/mm3, respectively. Sigmoid mucosa contained 57% CD3+CD4+ and 40%
      CD3+CD8+ T lymphocytes which calculates to 21,300 +/- 1,476/mm3 and 15,000 +/-
      275/mm3 T lymphocytes, respectively. Rectal mucosa had 57% CD3+CD4+ and 42%
      CD3+CD8+ or 21,577 +/- 332, and 17,090 +/- 1,206 cells/mm3, respectively. By
      comparison, sigmoid mucosal biopsies subjected to conventional collagenase
      digestion, mononuclear cell (MMC) isolation and staining for flow cytometry
      yielded 4,549 +/- 381/mm3 and 2,708 +/- 245/mm3 CD4+ and CD8+ T lymphocytes.
      These data suggest only ~20.7% recovery compared to IHC results for these
      markers. Further studies will determine if this reflects a selective bias in only
      CD3+, CD4+ and CD8+ T cells or can be generalized to all flow-analyzed cells from
      mucosal tissues for phenotyping and functional testing. 

PMID- 25856344
TI  - Siblings of patients with Crohn's disease exhibit a biologically relevant
      dysbiosis in mucosal microbial metacommunities.
AB  - OBJECTIVE: To determine the existence of mucosal dysbiosis in siblings of
      patients with Crohn's disease (CD) using 454 pyrosequencing and to
      comprehensively characterise and determine the influence of genotypical and
      phenotypical factors, on that dysbiosis. Siblings of patients with CD have
      elevated risk of developing CD and display aspects of disease phenotype,
      including faecal dysbiosis. Whether the mucosal microbiota is disrupted in these
      at-risk individuals is unknown. DESIGN: Rectal biopsy DNA was extracted from 21
      patients with quiescent CD, 17 of their healthy siblings and 19 unrelated healthy
      controls. Mucosal microbiota was analysed by 16S rRNA gene pyrosequencing and
      were classified into core and rare species. Genotypical risk was determined using
      Illumina Immuno BeadChip, faecal calprotectin by ELISA and blood T-cell phenotype
      by flow cytometry. RESULTS: Core microbiota of both patients with CD and healthy
      siblings was significantly less diverse than controls. Metacommunity profiling
      (Bray-Curtis (SBC) index) showed the sibling core microbial composition to be
      more similar to CD (SBC=0.70) than to healthy controls, whereas the sibling rare
      microbiota was more similar to healthy controls (SBC=0.42). Faecalibacterium
      prausnitzii contributed most to core metacommunity dissimilarity both between
      siblings and controls, and between patients and controls. Phenotype/genotype
      markers of CD risk significantly influenced microbiota variation between and
      within groups, of which genotype had the largest effect. CONCLUSIONS: Individuals
      with elevated CD-risk display mucosal dysbiosis characterised by reduced
      diversity of core microbiota and lower abundance of F. prausnitzii. This
      dysbiosis in healthy people at risk of CD implicates microbiological processes in
      CD pathogenesis.

PMID- 25856345
TI  - (-)-Liriopein B Suppresses Breast Cancer Progression via Inhibition of Multiple
      Kinases.
AB  - Numerous breast cancer patients who achieve an initial response to HER-targeted
      therapy rapidly develop resistance within one year, leading to treatment failure.
      Observations from clinical samples indicate that such resistance correlates with
      an increase in Src, EGFR, and PI3K/Akt activities and a decrease in PTEN
      activity. Furthermore, Akt survival signaling activation is also found in tumors
      treated by toxic chemotherapeutic agents. Because cotreatment with a PI3K
      inhibitor is a promising strategy to delay acquired resistance by preventing
      secondary gene activation, we therefore investigated the effects of a newly
      identified compound, (-)-Liriopein B (LB), on PI3K/Akt signaling activity in
      breast cancer cells. Our results showed that nontoxic doses of LB are able to
      inhibit AKT activation in both luminal-like MCF-7 and basal-like MDA-MB-231
      breast cancer cells. Low doses of LB also inhibited cell migration, invasion, and
      cancer-stem cell sphere formation. Suppression of EGF-induced EGFR and ERK1/2
      activation by LB might contribute in part to retardation of cancer progression.
      Furthermore, LB increases sensitivity of MDA-MB-231 cells to gefitinib in vitro,
      suggesting that EGFR may not be the only target of LB. Finally, a small scale in
      vitro kinase assay screen demonstrated that LB has a potent inhibitory effect on
      multiple kinases, including PI3K, Src, EGFR, Tie2, lck, lyn, RTK5, FGFR1, Abl,
      and Flt. In conclusion, this study demonstrates for the first time that the
      compound LB improves tumor therapeutic efficacy and suggests LB as a promising
      candidate for studying new leads in the development of kinase inhibitors. 

PMID- 25856346
TI  - Impact of North Carolina's motorcycle helmet law on hospital admissions and
      charges for care of traumatic brain injuries.
AB  - BACKGROUND North Carolina requires motorcyclists of all ages to wear federally
      approved safety helmets. The purpose of this article is to estimate the impact of
      this state law in terms of hospital admissions for traumatic brain injury (TBI)
      and associated hospital charges. METHODS Hospital admissions of North Carolina
      motorcyclists with TBIs and associated hospital charges in 2011 were extracted
      from the North Carolina Hospital Discharge Data system. We estimated hospital
      admissions and charges for the same year under the counterfactual condition of
      North Carolina without a universal motorcycle helmet law by using various
      substitutes (Florida, Pennsylvania, and South Carolina residents treated in North
      Carolina). RESULTS North Carolina's universal helmet law prevented an estimated
      190 to 226 hospital admissions of North Carolina motorcyclists with TBI in 2011.
      Averted hospital charges to taxpayer-funded sources (ie, government and public
      charges) were estimated to be between $9.5 million and $11.6 million for 2011,
      and total averted hospital charges for 2011 were estimated to be between $25.3
      million and $31.0 million. LIMITATIONS Cost estimates are limited to inpatients
      during the initial period of hospital care. This study was unable to capture long
      term health care costs and productivity losses incurred by North Carolina's TBI
      patients and their caregivers. CONCLUSIONS North Carolina's universal motorcycle
      helmet law generates health and economic benefits for the state and its
      taxpayers. 

PMID- 25856348
TI  - Another silent epidemic.

PMID- 25856347
TI  - A model of care for the uninsured population in Southeastern North Carolina.
AB  - BACKGROUND Cape Fear HealthNet is a unique collaborative model that was
      established to address coordination of care for low-income, uninsured individuals
      in the Lower Cape Fear Region of North Carolina. This model involves a
      centralized referral network to direct uninsured clients to medical homes among
      safety-net providers, a system for specialty referrals, and a short-term episodic
      or urgent care clinic (HealthNet Clinic) to address immediate or urgent health
      needs. METHODS We provide a descriptive analysis of patients seen in the episodic
      care clinic during the period August 2010 through July 2012. RESULTS Our data
      suggests that, compared to county population estimates, the HealthNet Clinic
      patients were more likely to be people of color, and a higher percentage of
      clinic patients had chronic diseases or lifestyle determinants of chronic
      diseases, such as diabetes, obesity, or smoking. Almost half of clinic patients
      (43.7%) required some type of laboratory or diagnostic service; less than 10% of
      clinic patients were referred to a specialty provider. Findings from this study
      can inform community collaborative efforts and planning by other safety-net
      providers to help leverage limited resources and increase access to care among
      uninsured individuals in North Carolina. LIMITATIONS Patient characteristics
      cannot be generalized to all uninsured individuals in the region, as there are
      other safety-net providers in the Lower Cape Fear region, and their clinical data
      were not included in this analysis. CONCLUSIONS The Cape Fear HealthNet
      collaborative model is successful in directing patients, many of whom have
      significant chronic illness burdens, to a medical home in the community safety
      net. 

PMID- 25856349
TI  - Traumatic brain injury in North Carolina: the state of the state today.
AB  - This issue brief provides an overview of the "state of the state" for traumatic
      brain injury (TBI) issues and challenges in North Carolina. A previous issue of
      the North Carolina Medical Journal discussed this topic approximately 14 years
      ago, and this issue brief showcases changes and advances since that time.
      Collectively, articles in the current issue highlight the current epidemiology of
      TBI; the rapidly advancing and critical topic of concussions; special populations
      where TBI is seen more frequently, such as elderly individuals and veterans;
      advances in TBI-related treatments; and the all-important family perspective on
      TBI. Additionally, this issue brief discusses key developments and advances in
      the state related to a statewide needs assessment; legislative and policy
      actions, including a new sports concussion awareness act and a significantly
      revised definition of TBI as it relates to special education classification; and
      ongoing exploration of evidence-based community services that have the potential
      to improve our system of care for adults with TBI. Finally, ongoing challenges
      are detailed with the intention of pushing the state to become one of the
      nation's leaders in TBI services. 

PMID- 25856350
TI  - Sports-related concussions.
AB  - Concussions are an inherent part of collision sports such as football and soccer.
      As a subset of traumatic brain injury, concussions are neurometabolic events that
      cause transient neurologic dysfunction. Following a concussion, some athletes
      require longer neurologic recovery than others. Education and intervention aimed
      at prevention and management can minimize the long-term sequelae of sports
      related concussions. 

PMID- 25856351
TI  - Gfeller-Waller Concussion Awareness Act.

PMID- 25856352
TI  - Sport-related concussions: paranoia or legitimate concern?

PMID- 25856353
TI  - Traumatic brain injury and behavioral health: the state of treatment and policy.
AB  - In the United States, 1.7 million people sustain a traumatic brain injury (TBI)
      each year, of whom 52,000 die and 275,000 are hospitalized. Societal costs of TBI
      total at least $10 billion. In this article, we review the current state of
      treatment and policy and make recommendations that would benefit TBI survivors
      with behavioral health comorbidities. 

PMID- 25856354
TI  - Traumatic brain injury among North Carolina's veterans.
AB  - This article describes the difficulty of diagnosing traumatic brain injury (TBI),
      treatment protocols provided through the military, an alternative therapy with
      scientific evidence of its effectiveness in repairing injured brain tissue,
      challenges faced by brain-injured veterans seeking community reintegration, and
      state services that are available to help veterans. 

PMID- 25856355
TI  - Treating persons with traumatic brain injury: history and updates.
AB  - The scientific traumatic brain injury (TBI) literature chronicles 50 years of
      epidemiologic data, neurobehavioral and cognitive symptoms, diagnostic tools for
      measuring outcomes, and treatments for persons with TBI. In this article, we
      review the state of our knowledge about TBI causes and symptom complexities,
      evidence-based treatments, and ongoing treatment needs. 

PMID- 25856356
TI  - Return-to-school protocols following a concussion.

PMID- 25856358
TI  - A caregiver's perspective on traumatic brain injury.

PMID- 25856357
TI  - Falls and traumatic brain injury among older adults.
AB  - This commentary discusses traumatic brain injury (TBI) related to falls among
      elderly individuals, as well as common TBI sequelae and their treatment. It also
      discusses the current understanding of TBI-related dementia and chronic traumatic
      encephalopathy. 

PMID- 25856359
TI  - Prehospital care of traumatic brain injury in North Carolina.
AB  - Traumatic brain injury results in more than 140,000 visits to North Carolina
      emergency departments annually. North Carolina first implemented a systematically
      organized approach to brain injury management in 1967, and the state's emergency
      medical services community continues to optimize patient care by incorporating
      evolving knowledge into protocols and procedures. 

PMID- 25856360
TI  - Traumatic brain injuries in North Carolina.

PMID- 25856361
TI  - Traumatic brain injury clubhouses in North Carolina.

PMID- 25856362
TI  - An ACO view on Medicaid reform.

PMID- 25856363
TI  - North Carolina medical legacy.

PMID- 25856365
TI  - Omega 3 fatty acids for preventing or slowing the progression of age-related
      macular degeneration.
AB  - BACKGROUND: Evidence from animal models and observational studies in humans has
      suggested that there is an inverse relationship between dietary intake of omega 3
      long-chain polyunsaturated fatty acids (LCPUFA) and risk of developing age
      related macular degeneration (AMD) or progression to advanced AMD. OBJECTIVES: To
      review the evidence that increasing the levels of omega 3 LCPUFA in the diet
      (either by eating more foods rich in omega 3 or by taking nutritional
      supplements) prevents AMD or slows the progression of AMD. SEARCH METHODS: We
      searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials
      Register) (2015, Issue 1), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non
      Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to February
      2015), EMBASE (January 1980 to February 2015), Latin American and Caribbean
      Health Sciences Literature Database (LILACS) (January 1982 to February 2015), the
      ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov
      (www.clinicaltrials.gov) and the World Health Organization (WHO) International
      Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did
      not use any date or language restrictions in the electronic searches for trials.
      We last searched the electronic databases on 2 February 2015. SELECTION CRITERIA:
      We included randomised controlled trials (RCTs) where increased dietary intake of
      omega 3 LCPUFA was compared to placebo or no intervention with the aim of
      preventing the development of AMD, or slowing its progression. DATA COLLECTION
      AND ANALYSIS: Both authors independently selected studies, assessed them for risk
      of bias and extracted data. One author entered data into RevMan 5 and the other
      author checked the data entry. We conducted a meta-analysis for one primary
      outcome, progression of AMD, using a fixed-effect inverse variance model. MAIN
      RESULTS: We included two RCTs in this review, in which 2343 participants with AMD
      were randomised to receive either omega 3 fatty acid supplements or a placebo.
      The trials, which had a low risk of bias, were conducted in the USA and France.
      Overall, there was no evidence that people who took omega 3 fatty acid
      supplements were at decreased (or increased risk) of progression to advanced AMD
      (pooled hazard ratio (HR) 0.96, 95% confidence interval (CI) 0.84 to 1.10, high
      quality evidence). Similarly, people taking these supplements were no more (or
      less) likely to lose 15 or more letters of visual acuity (USA study HR 0.96, 95%
      CI 0.84 to 1.10; French study at 36 months risk ratio (RR) 1.25, 95% CI 0.69 to
      2.26, participants = 230). The number of adverse events was similar in the
      intervention and placebo groups (USA study participants with one or more serious
      adverse event RR 1.00, 95% CI 0.91 to 1.09, participants = 2080; French study
      total adverse events RR 1.05, 95% CI 0.97 to 1.13, participants = 263). AUTHORS'
      CONCLUSIONS: This review found that omega 3 LCPUFA supplementation in people with
      AMD for periods up to five years does not reduce the risk of progression to
      advanced AMD or the development of moderate to severe visual loss. No published
      randomised trials were identified on dietary omega 3 fatty acids for primary
      prevention of AMD. Currently available evidence does not support increasing
      dietary intake of omega 3 LCPUFA for the explicit purpose of preventing or
      slowing the progression of AMD.

PMID- 25856366
TI  - Function of the BTK pathway in B-cell malignancies.

PMID- 25856364
TI  - Removal of Metabolic Liabilities Enables Development of Derivatives of Procaspase
      Activating Compound 1 (PAC-1) with Improved Pharmacokinetics.
AB  - Procaspase-activating compound 1 (PAC-1) is an o-hydroxy-N-acylhydrazone that
      induces apoptosis in cancer cells by chelation of labile inhibitory zinc from
      procaspase-3. PAC-1 has been assessed in a wide variety of cell culture
      experiments and in vivo models of cancer, with promising results, and a phase 1
      clinical trial in cancer patients has been initiated (NCT02355535). For certain
      applications, however, the in vivo half-life of PAC-1 could be limiting. Thus,
      with the goal of developing a compound with enhanced metabolic stability, a
      series of PAC-1 analogues were designed containing modifications that
      systematically block sites of metabolic vulnerability. Evaluation of the library
      of compounds identified four potentially superior candidates with comparable
      anticancer activity in cell culture, enhanced metabolic stability in liver
      microsomes, and improved tolerability in mice. In head-to-head experiments with
      PAC-1, pharmacokinetic evaluation in mice demonstrated extended elimination half
      lives and greater area under the curve values for each of the four compounds,
      suggesting them as promising candidates for further development. 

PMID- 25856368
TI  - Clinical use of BTK inhibitors.

PMID- 25856367
TI  - Clinical trial data on the BTK pathway in B-cell malignancies.

PMID- 25856369
TI  - The importance of the BTK pathway in B-cell malignancies: discussion.

PMID- 25856371
TI  - The use of recommended communication techniques by Maryland family physicians and
      pediatricians.
AB  - BACKGROUND: Health literacy experts and the American Medical Association have
      developed recommended communication techniques for healthcare providers given
      that effective communication has been shown to greatly improve health outcomes.
      The purpose of this study was to determine the number and types of communication
      techniques routinely used by Maryland physicians. METHODS: In 2010, a 30-item
      survey was mailed to a random sample of 1,472 Maryland family physicians and
      pediatricians, with 294 surveys being returned and usable. The survey contained
      questions about provider and practice characteristics, and 17 items related to
      communication techniques, including seven basic communication techniques.
      Physicians' use of recommended communication techniques was analyzed using
      descriptive statistics, analysis of variance, and ordinary least squares
      regression. RESULTS: Family physicians routinely used an average of 6.6 of the 17
      total techniques and 3.3 of the seven basic techniques, whereas pediatricians
      routinely used 6.4 and 3.2 techniques, respectively. The use of simple language
      was the only technique that nearly all physicians routinely utilized (Family
      physicians, 91%; Pediatricians, 93%). Physicians who had taken a communications
      course used significantly more techniques than those who had not. Physicians with
      a low percentage of patients on Medicaid were significantly less likely to use
      the recommended communication techniques compared to those providers who had high
      proportion of their patient population on Medicaid. CONCLUSIONS: Overall, the use
      of recommended communication techniques was low. Additionally, many physicians
      were unsure of the effectiveness of several of the recommended techniques, which
      could suggest that physicians are unaware of valuable skills that could enhance
      their communication. The findings of this study suggest that communications
      training should be given a higher priority in the medical training process in the
      United States.

PMID- 25856370
TI  - Clinically Meaningful Rehabilitation Outcomes of Low Vision Patients Served by
      Outpatient Clinical Centers.
AB  - IMPORTANCE: To facilitate comparative clinical outcome research in low vision
      rehabilitation, we must use patient-centered measurements that reflect clinically
      meaningful changes in visual ability. OBJECTIVE: To quantify the effects of
      currently provided low vision rehabilitation (LVR) on patients who present for
      outpatient LVR services in the United States. DESIGN, SETTING, AND PARTICIPANTS:
      Prospective, observational study of new patients seeking outpatient LVR services.
      From April 2008 through May 2011, 779 patients from 28 clinical centers in the
      United States were enrolled in the Low Vision Rehabilitation Outcomes Study. The
      Activity Inventory, a visual function questionnaire, was administered to measure
      overall visual ability and visual ability in 4 functional domains (reading,
      mobility, visual motor function, and visual information processing) at baseline
      and 6 to 9 months after usual LVR care. The Geriatric Depression Scale, Telephone
      Interview for Cognitive Status, and Medical Outcomes Study 36-Item Short-Form
      Health Survey physical functioning questionnaires were also administered to
      measure patients' psychological, cognitive, and physical health states,
      respectively, and clinical findings of patients were provided by study centers.
      MAIN OUTCOMES AND MEASURES: Mean changes in the study population and minimum
      clinically important differences in the individual in overall visual ability and
      in visual ability in 4 functional domains as measured by the Activity Inventory.
      RESULTS: Baseline and post-rehabilitation measures were obtained for 468
      patients. Minimum clinically important differences (95% CIs) were observed in
      nearly half (47% [95% CI, 44%-50%]) of patients in overall visual ability. The
      prevalence rates of patients with minimum clinically important differences in
      visual ability in functional domains were reading (44% [95% CI, 42%-48%]), visual
      motor function (38% [95% CI, 36%-42%]), visual information processing (33% [95%
      CI, 31%-37%]), and mobility (27% [95% CI, 25%-31%]). The largest average effect
      size (Cohen d = 0.87) for the population was observed in overall visual ability.
      Age (P = .006) was an independent predictor of changes in overall visual ability,
      and logMAR visual acuity (P = .002) was predictive of changes in visual
      information processing. CONCLUSIONS AND RELEVANCE: Forty-four to fifty percent of
      patients presenting for outpatient LVR show clinically meaningful differences in
      overall visual ability after LVR, and the average effect sizes in overall visual
      ability are large, close to 1 SD.

PMID- 25856372
TI  - More dialectical thinking, less creativity? The relationship between dialectical
      thinking style and creative personality: the case of China.
AB  - People use dialectical thinking to be holistic, reconcile contradictions, and
      emphasize changes when processing information and managing problems. Using a
      questionnaire survey, this study examined the relationship between dialectical
      thinking and creative personality in the Chinese culture, which encourages a
      holistic and collective thinking style. Undergraduates majoring in different
      subjects and adults in different professions were surveyed. The results showed
      that 1) compared with undergraduates majoring in art and adults from the design
      industry, undergraduates majoring in other disciplines significantly showed the
      least creative personality; 2) the highest score for dialectical thinking was
      found in the group of undergraduates who majored in other disciplines, followed
      by the adult group, and the undergraduates majoring in art had the lowest score;
      and 3) A negative relationship between dialectical thinking and creative
      personality was found mostly in the UMA group. The limitations of this study and
      suggestions for future research are discussed. 

PMID- 25856373
TI  - Use of an electronic medication administration record (eMAR) for surveillance of
      medication omissions: results of a one year study of antimicrobials in the
      inpatient setting.
AB  - INTRODUCTION: Medication administration omissions (MAO) are usually considered
      medication errors but not all MAO are clinically relevant. We determined the
      frequency of clinically relevant MAO of antimicrobial drugs in adult hospitals in
      Calgary, Alberta, Canada based on electronic medication administration record
      (eMAR). METHODS: We examined 2011 data from eMAR records on medical wards and
      developed a reproducible assessment scheme to categorize and determine clinical
      relevance of MAO. We applied this scheme to records from 2012 in a retrospective
      cohort study to quantify clinically relevant MAO. Significant predictors of
      clinically relevant MAO were identified. RESULTS: A total of 294,718 dose records
      were assessed of which 10,282 (3.49%) were for doses not administered. Among
      these 4903 (1.66% of total); 47.68% of MAO were considered clinically relevant.
      Significant positive predictors of clinically relevant MAO included inhaled (OR
      4.90, 95% CI 3.54-6.94) and liquid oral (OR 1.32, 95% CI 1.18-1.47) route of
      medication compared to solid oral and irregular dose schedules. Evening nursing
      shift compared to night shift (OR 0.77 95% CI 0.70-0.85) and parenteral (OR 0.50,
      95% CI 0.46-0.54) were negative predictors, The commonest reasons for relevant
      MAO were patient preference, unspecified reason, administration access issues,
      drug not available or patient condition. CONCLUSION: Assessment of MAO by review
      of computer records provides a greater scope and sample size than directly
      observed medication administration assessments without "observer" effect. We
      found that MAO of antimicrobials in inpatients were uncommon but were seen more
      frequently with orally administered antimicrobials which may have significance to
      antimicrobial stewardship initiatives.

PMID- 25856374
TI  - Local difference measures between complex networks for dynamical system model
      evaluation.
AB  - A faithful modeling of real-world dynamical systems necessitates model
      evaluation. A recent promising methodological approach to this problem has been
      based on complex networks, which in turn have proven useful for the
      characterization of dynamical systems. In this context, we introduce three local
      network difference measures and demonstrate their capabilities in the field of
      climate modeling, where these measures facilitate a spatially explicit model
      evaluation.Building on a recent study by Feldhoff et al. [8] we comparatively
      analyze statistical and dynamical regional climate simulations of the South
      American monsoon system [corrected]. types of climate networks representing
      different aspects of rainfall dynamics are constructed from the modeled
      precipitation space-time series. Specifically, we define simple graphs based on
      positive as well as negative rank correlations between rainfall anomaly time
      series at different locations, and such based on spatial synchronizations of
      extreme rain events. An evaluation against respective networks built from daily
      satellite data provided by the Tropical Rainfall Measuring Mission 3B42 V7
      reveals far greater differences in model performance between network types for a
      fixed but arbitrary climate model than between climate models for a fixed but
      arbitrary network type. We identify two sources of uncertainty in this respect.
      Firstly, climate variability limits fidelity, particularly in the case of the
      extreme event network; and secondly, larger geographical link lengths render link
      misplacements more likely, most notably in the case of the anticorrelation
      network; both contributions are quantified using suitable ensembles of surrogate
      networks. Our model evaluation approach is applicable to any multidimensional
      dynamical system and especially our simple graph difference measures are highly
      versatile as the graphs to be compared may be constructed in whatever way
      required. Generalizations to directed as well as edge- and node-weighted graphs
      are discussed.

PMID- 25856375
TI  - Opportunities for Prevention: Assessing Where Low-Income Patients Seek Care for
      Preventable Coronary Artery Disease.
AB  - The Affordable Care Act has many aspects that are aimed at improving health care
      for all Americans, including mandated insurance coverage for individuals, as well
      as required community health needs assessments (CHNAs), and reporting of
      investments in community benefit by nonprofit hospitals in order to maintain tax
      exemptions. Although millions of Americans have gained access to health
      insurance, many--often the most vulnerable--remain uninsured, and will continue
      to depend on hospital community benefits for care. Understanding where patients
      go for care can assist hospitals and communities to develop their CHNA and
      implementation plans in order to focus resources where the need for prevention is
      greatest. This study evaluated patient care-seeking behavior among patients with
      coronary artery disease (CAD) in Florida in 2008--analyzed in 2013--to assess
      whether low-income patients accessed specific safety net hospitals for treatment
      or received care from hospitals that were geographically closer to their
      residence. This study found evidence that low-income patients went to hospitals
      that treated more low-income patients, regardless of where they lived. The
      findings demonstrate that hospitals-especially public safety net hospitals with a
      tradition of treating low-income patients suffering from CAD-should focus
      prevention activities where low-income patients reside.

PMID- 25856376
TI  - Response characteristics of soil fractal features to different land uses in
      typical purple soil watershed.
AB  - As a fundamental characteristic of soil physical properties, the soil Particle
      Size Distribution (PSD) is important in the research on soil moisture migration,
      solution transformation, and soil erosion. In this research, the PSD
      characteristics with distinct methods in different land uses are analyzed. The
      results show that the upper bound of the volume domain of the clay domain ranges
      from 5.743 MUm to 5.749 MUm for all land-use types. For the silt domain of purple
      soil, the value ranges among 286.852~286.966 MUm. For all purple soil land-use
      types, the order of the volume domain fractal dimensions is D clay<D silt<D sand.
      However, the values of D silt and D sand in the Pinus massoniana Lamb, Robinia
      pseudoacacia L and Ipomoea batatas are all higher than the corresponding values
      in the Citrus reticulate Blanco and Setaria viridis. Moreover, in all the land
      use types, all of the parameters in volume domain fractal dimension (Dvi) are
      higher than the corresponding parameter values from the United States Department
      of Agriculture (Dvi(U)). The correlation study between the volume domain fractal
      dimension and the soil properties shows that the intensity of correlation to the
      soil texture and soil organic matter has the order as: D silt>D silt(U)>D sand
      (U)>D sand and D silt>D silt(U)>D sand>D sand(U), respectively. As it is compared
      with all Dvi, the D silt has the most significant correlativity to the soil
      texture and organic matter in different land uses of the typical purple soil
      watersheds. Therefore, Dsilt will be a potential indictor for evaluating the
      proportion of fine particles in the PSD, as well as a key measurement in soil
      quality and productivity studies.

PMID- 25856377
TI  - Impact of beaver dams on abundance and distribution of anadromous salmonids in
      two lowland streams in Lithuania.
AB  - European beaver dams impeded movements of anadromous salmonids as it was
      established by fishing survey, fish tagging and redd counts in two lowland
      streams in Lithuania. Significant differences in abundancies of other litophilic
      fish species and evenness of representation by species in the community were
      detected upstream and downstream of the beaver dams. Sea trout parr marked with
      RFID tags passed through several successive beaver dams in upstream direction,
      but no tagged fish were detected above the uppermost dam. Increase in abundances
      of salmonid parr in the stream between the beaver dams and decrease below the
      dams were recorded in November, at the time of spawning of Atlantic salmon and
      sea trout, but no significant changes were detected in the sections upstream of
      the dams. After construction of several additional beaver dams in the downstream
      sections of the studied streams, abundance of Atlantic salmon parr downstream of
      the dams decreased considerably in comparison with that estimated before
      construction. 

PMID- 25856378
TI  - In vitro microtumors provide a physiologically predictive tool for breast cancer
      therapeutic screening.
AB  - Many anti-cancer drugs fail in human trials despite showing efficacy in
      preclinical models. It is clear that the in vitro assays involving 2D monoculture
      do not reflect the complex extracellular matrix, chemical, and cellular
      microenvironment of the tumor tissue, and this may explain the failure of 2D
      models to predict clinical efficacy. We first optimized an in vitro microtumor
      model using a tumor-aligned ECM, a tumor-aligned medium, MCF-7 and MDA-MB-231
      breast cancer spheroids, human umbilical vein endothelial cells, and human
      stromal cells to recapitulate the tissue architecture, chemical environment, and
      cellular organization of a growing and invading tumor. We assayed the microtumor
      for cell proliferation and invasion in a tumor-aligned extracellular matrix,
      exhibiting collagen deposition, acidity, glucose deprivation, and hypoxia. We
      found maximal proliferation and invasion when the multicellular spheroids were
      cultured in a tumor-aligned medium, having low pH and low glucose, with 10% fetal
      bovine serum under hypoxic conditions. In a 7-day assay, varying doses of
      fluorouracil or paclitaxel had differential effects on proliferation for MCF-7
      and MDA-MB-231 tumor spheroids in microtumor compared to 2D and 3D monoculture.
      The microtumors exhibited a tumor morphology and drug response similar to
      published xenograft data, thus demonstrating a more physiologically predictive in
      vitro model. 

PMID- 25856379
TI  - Impact of endoscopic lung volume reduction on right ventricular myocardial
      function.
AB  - INTRODUCTION: Endoscopic lung volume reduction (ELVR) provides a minimally
      invasive therapy for patients with severe lung emphysema. As its impact on right
      ventricular (RtV) function is undefined, we examined the extent of RtV functional
      changes following ELVR, as assessed by use of speckle tracking-based RtV
      deformation analysis. METHODS: We enrolled 32 patients with severe emphysematous
      COPD scheduled for bronchoscopic LVR using endobronchial valves (Zephyr, PulmonX,
      Inc.), comprising 16 matched clinical responders and 16 non-responders.
      Echocardiography was conducted one day prior to ELVR and at an eight-week
      postprocedural interval. RESULTS: Patients were predominantly of late middle-age
      (65.8 +/- 8.7 yrs), male (62.5%) and presented advanced COPD emphysema (means
      FEV1 and RV: 32.6% and 239.1% of predicted, respectively). After ELVR, RtV apical
      longitudinal strain improved significantly in the total study cohort (-7.96 +/-
      7.02% vs. -13.35 +/- 11.48%, p = 0.04), whereas there were no significant changes
      in other parameters of RtV function such as RtV global longitudinal strain, TAPSE
      or pulmonary arterial systolic pressure. In responding patients, 6MWT-improvement
      correlated with a decrease in NT-proBNP (Pearson's r: -0.53, p = 0.03). However,
      clinical non-responders did not exhibit any RtV functional improvement.
      DISCUSSION: ELVR beneficially impacts RtV functional parameters. Speckle tracking
      based RtV apical longitudinal strain analysis allows early determination of RtV
      contractile gain and identification of clinical responsiveness.

PMID- 25856381
TI  - Correction: DNA barcoding of Japanese click beetles (Coleoptera, Elateridae).

PMID- 25856380
TI  - Nutritional status of the cauliflower cultivar 'verona' grown with omission of
      out added macronutrients.
AB  - Knowledge of plant nutritional status allows an understanding of the
      physiological responses of plants to crop fertilization. A hydroponic experiment
      evaluated the symptoms of macronutrient deficiency in cauliflower 'Verona' and
      determined: a) the macronutrient contents of foliar tissues when visual symptoms
      were observed, b) macronutrients content of foliar and inflorescence tissues at
      harvest. The effect of nutrient deficiency on inflorescence mass was also
      evaluated. Nitrogen deficiency caused chlorosis followed by purple color in the
      old leaves, while P deficiency caused only chlorosis in old leaves. Chlorosis at
      the edge of old leaves progressing to the center of the leaves was observed with
      the omission of K, and after was observed necrosis in the chlorotic areas. Ca
      deficiency caused tip burn in new leaves, while Mg deficiency caused internerval
      chlorosis in old leaves. The omission of each macronutrient reduced inflorescence
      dry matter. This deleterious effect was larger for N, P, and K deficiencies,
      reducing inflorescence dry matter by 87, 49, and 42%, respectively. When the
      nutrient solutions without N, P, K, Ca, or Mg were supplied to cauliflower
      plants, the macronutrient contents at harvest were 8.8, 0.6, 3.5, 13.0, and 0.8 g
      kg-1 in the foliar tissues and 27.3, 2.2, 21.6, 1.1, and 0.7 g kg-1 in the
      inflorescence tissues, respectively. 

PMID- 25856382
TI  - High Rate of Cardiac Abnormalities in a Postmortem Analysis of Patients Suffering
      From Liver Cirrhosis.
AB  - BACKGROUND: Cirrhotic cardiomyopathy is a recently defined cardiac disorder in
      patients with end-stage liver disease. The frequency and exact manifestations of
      cardiac changes in liver cirrhosis is unknown. GOALS: We aim to describe cardiac
      changes in a large autopsy study of patients with liver cirrhosis. STUDY:
      Postmortem data from 895 individuals with liver cirrhosis of different origin
      autopsied from 1995 to 2010 were analyzed. A total of 236 patients were excluded,
      mostly due to an advanced age above 70 years. The remaining 659 patients were
      assigned to 4 subgroups according to the etiology of cirrhosis: alcoholic
      cirrhosis (57.4%), nonalcoholic steatohepatitis (4.2%), viral hepatitis (9.3%),
      and cryptogenic cirrhosis (29.1%). Predefined clinical and cardiac parameters
      were assessed in these groups and compared by univariate and multivariate
      analyses to an age-matched and sex-matched control group including 40 deceased
      patients without evidence of chronic liver disease. RESULTS: A critical heart
      weight (24%, P=0.024), hypertrophy of the right ventricle (24%, P<0.001), and
      dilatation of the right ventricle (36%, P=0.040) were significantly more frequent
      in the cirrhosis group compared with noncirrhotic controls. Cirrhosis patients
      had a greater risk for high-grade coronary sclerosis (30%, P=0.019). The etiology
      of cirrhosis was independently associated with hypertrophy and dilatation of the
      right ventricle, with nonalcoholic steatohepatitis patients being at the highest
      risk. CONCLUSION: Our results demonstrate a high rate of right-ventricular
      abnormalities and coronary sclerosis in individuals suffering from liver
      cirrhosis regardless of the etiology of cirrhosis.

PMID- 25856383
TI  - Renal Function in Chronic Hepatitis B Patients Treated With Tenofovir Disoproxil
      Fumarate or Entecavir Monotherapy: A Matched Case-Cohort Study.
AB  - BACKGROUND AND AIMS: Tenofovir (TDF)-associated renal dysfunction has been
      described in various studies of human immunodeficiency virus-infected patients.
      Our goal is to examine the incidence and magnitude of decrease in renal function
      in chronic hepatitis B patients treated with TDF. METHODS: We performed a case
      cohort study of 103 patients on TDF 300 mg and 103 patients unexposed to TDF
      (Entecavir) at 4 centers, who were matched for age+/-10 years, sex, and baseline
      estimated glomerular filtration rate (eGFR) group. Calculation and evaluation of
      eGFR were performed with both the Cockcroft-Gault formula and the Modification of
      Diet in Renal Disease formula. RESULTS: The exposed and unexposed populations
      were well matched with a similar mean age (44+/-10 y), proportion of male
      patients (63.1%), and baseline eGFR groups (86.4% unimpaired). There was no
      significant difference in the proportion of patients reclassified to a more
      severe renal classification (RMSRC) or in the proportion of patients with
      decrease in eGFR of >=20% in those exposed to TDF versus control. The incidence
      density for RMSRC was 7.4 cases per 100 patient-years in the exposed group
      compared with 11.5 cases per 100 patient-years in the unexposed group (95% CI,
      0.31-1.34). The relative risk of exposed to unexposed was 0.64 (95% CI, 0.31
      1.34). On Cox proportional hazard analysis following adjustment for sex, age,
      baseline diagnosis hypertension, diabetes, impaired baseline renal function, and
      cirrhosis, TDF was not a predictor for RMSRC or decrease in eGFR>=20%.
      CONCLUSIONS: TDF treatment was not an independent predictor for significant
      deterioration of renal function. Renal function of chronic hepatitis B patients
      on antiviral therapy should be monitored, especially in those who are older
      and/or with mildly impaired renal function.

PMID- 25856384
TI  - Design factors of intravascular dual frequency transducers for super-harmonic
      contrast imaging and acoustic angiography.
AB  - Imaging of coronary vasa vasorum may lead to assessment of the vulnerable plaque
      development in diagnosis of atherosclerosis diseases. Dual frequency transducers
      capable of detection of microbubble super-harmonics have shown promise as a new
      contrast-enhanced intravascular ultrasound (CE-IVUS) platform with the capability
      of vasa vasorum imaging. Contrast-to-tissue ratio (CTR) in CE-IVUS imaging can be
      closely associated with low frequency transmitter performance. In this paper,
      transducer designs encompassing different transducer layouts, transmitting
      frequencies, and transducer materials are compared for optimization of imaging
      performance. In the layout selection, the stacked configuration showed superior
      super-harmonic imaging compared with the interleaved configuration. In the
      transmitter frequency selection, a decrease in frequency from 6.5 MHz to 5 MHz
      resulted in an increase of CTR from 15 dB to 22 dB when receiving frequency was
      kept constant at 30 MHz. In the material selection, the dual frequency transducer
      with the lead magnesium niobate-lead titanate (PMN-PT) 1-3 composite transmitter
      yielded higher axial resolution compared to single crystal transmitters (70 MUm
      compared to 150 MUm pulse length). These comparisons provide guidelines for the
      design of intravascular acoustic angiography transducers. 

PMID- 25856385
TI  - Bud protection: a key trait for species sorting in a forest-savanna mosaic.
AB  - Contrasting fire regimes maintain patch mosaics of savanna, thicket and forest
      biomes in many African subtropical landscapes. Species dominating each biome are
      thus expected to display distinct fire-related traits, commonly thought to be
      bark related. Recent Australian savanna research suggests that bud position, not
      bark protection alone, determines fire resilience via resprouting. We tested
      first how bud position influences resprouting ability in 17 tree species. We then
      compared the effect of both bark-related protection and bud position on the
      distribution of 63 tree species in 253 transects in all three biomes. Tree
      species with buds positioned deep under bark had a higher proportion of post-fire
      aboveground shoot resprouting. Species with low bud protection occurred in fire
      prone biomes only if they could root-sucker. The effect of bud protection was
      supported by a good relationship between species bud protection and distribution
      across a gradient of fire frequency. Bud protection and high bark production are
      required to survive frequent fires in savanna. Forests are fire refugia hosting
      species with little or no bud protection and thin bark. Root-suckering species
      occur in the three biomes, suggesting that fire is not the only factor filtering
      this functional type. 

PMID- 25856386
TI  - Mineral density volume gradients in normal and diseased human tissues.
AB  - Clinical computed tomography provides a single mineral density (MD) value for
      heterogeneous calcified tissues containing early and late stage pathologic
      formations. The novel aspect of this study is that, it extends current
      quantitative methods of mapping mineral density gradients to three dimensions,
      discretizes early and late mineralized stages, identifies elemental distribution
      in discretized volumes, and correlates measured MD with respective calcium (Ca)
      to phosphorus (P) and Ca to zinc (Zn) elemental ratios. To accomplish this, MD
      variations identified using polychromatic radiation from a high resolution micro
      computed tomography (micro-CT) benchtop unit were correlated with elemental
      mapping obtained from a microprobe X-ray fluorescence (XRF) using synchrotron
      monochromatic radiation. Digital segmentation of tomograms from normal and
      diseased tissues (N=5 per group; 40-60 year old males) contained significant
      mineral density variations (enamel: 2820-3095 mg/cc, bone: 570-1415 mg/cc,
      cementum: 1240-1340 mg/cc, dentin: 1480-1590 mg/cc, cementum affected by
      periodontitis: 1100-1220 mg/cc, hypomineralized carious dentin: 345-1450 mg/cc,
      hypermineralized carious dentin: 1815-2740 mg/cc, and dental calculus: 1290-1770
      mg/cc). A plausible linear correlation between segmented MD volumes and elemental
      ratios within these volumes was established, and Ca/P ratios for dentin (1.49),
      hypomineralized dentin (0.32-0.46), cementum (1.51), and bone (1.68) were
      observed. Furthermore, varying Ca/Zn ratios were distinguished in adapted
      compared to normal tissues, such as in bone (855-2765) and in cementum (595-990),
      highlighting Zn as an influential element in prompting observed adaptive
      properties. Hence, results provide insights on mineral density gradients with
      elemental concentrations and elemental footprints that in turn could aid in
      elucidating mechanistic processes for pathologic formations.

PMID- 25856387
TI  - Telomerase activity impacts on Epstein-Barr virus infection of AGS cells.
AB  - The Epstein-Barr virus (EBV) is transmitted from host-to-host via saliva and is
      associated with epithelial malignancies including nasopharyngeal carcinoma (NPC)
      and some forms of gastric carcinoma (GC). Nevertheless, EBV does not transform
      epithelial cells in vitro where it is rapidly lost from infected primary
      epithelial cells or epithelial tumor cells. Long-term infection by EBV, however,
      can be established in hTERT-immortalized nasopharyngeal epithelial cells. Here,
      we hypothesized that increased telomerase activity in epithelial cells enhances
      their susceptibility to infection by EBV. Using HONE-1, AGS and HEK293 cells we
      generated epithelial model cell lines with increased or suppressed telomerase
      activity by stable ectopic expression of hTERT or of a catalytically inactive,
      dominant negative hTERT mutant. Infection experiments with recombinant prototypic
      EBV (rB95.8), recombinant NPC EBV (rM81) with increased epithelial cell tropism
      compared to B95.8, or recombinant B95.8 EBV with BZLF1-knockout that is not able
      to undergo lytic replication, revealed that infection frequencies positively
      correlate with telomerase activity in AGS cells but also partly depend on the
      cellular background. AGS cells with increased telomerase activity showed
      increased expression mainly of latent EBV genes, suggesting that increased
      telomerase activity directly acts on the EBV infection of epithelial cells by
      facilitating latent EBV gene expression early upon virus inoculation. Thus, our
      results indicate that infection of epithelial cells by EBV is a very selective
      process involving, among others, telomerase activity and cellular background to
      allow for optimized host-to-host transmission via saliva. 

PMID- 25856388
TI  - Trace elements in scalp hair samples from patients with relapsing-remitting
      multiple sclerosis.
AB  - BACKGROUND: Epidemiological studies have suggested a possible role of trace
      elements (TE) in the etiology of several neurological diseases including Multiple
      Sclerosis (MS). Hair analysis provides an easy tool to quantify TE in human
      subjects, including patients with neurodegenerative diseases. OBJECTIVE: To
      compare TE levels in scalp hair from patients with MS and healthy controls from
      the same geographic area (Sicily). METHODS: ICP-MS was used to determine the
      concentrations of 21 elements (Ag, Al, As, Ba, Cd, Co, Cr, Cu, Fe, Li, Mn, Mo,
      Ni, Pb, Rb, Sb, Se, Sr, U, V and Zn) in scalp hair of 48 patients with relapsing
      remitting Multiple Sclerosis compared with 51 healthy controls. RESULTS: MS
      patients showed a significantly lower hair concentration of aluminum and rubidium
      (median values: Al = 3.76 MUg/g vs. 4.49 MUg/g and Rb = 0.007 MUg/g vs. 0.01
      MUg/g;) and higher hair concentration of U (median values U: 0.014 MUg/g vs.
      0.007 MUg/g) compared to healthy controls. The percentages of MS patients showing
      hair elemental concentrations greater than the 95th percentile of controls were
      20% for Ni, 19% for Ba and U, and 15% for Ag, Mo and Se. Conversely, the
      percentages of MS patients showing hair elemental concentrations lower than the
      5th percentile of healthy controls were 27% for Al, 25% for Rb, 22% for Ag, 19%
      for Fe, and 16% for Pb. No significant association was found between levels of
      each TE and age, disease duration or Expanded Disability Status Scale (EDSS)
      score. After stratification by gender, healthy subjects did not show any
      significant difference in trace element levels, while MS patients showed
      significant differences (p<0.01) for the concentrations of Ag, Cr, Fe, Ni and Sr.
      No significant differences were also found, at p<0.01, in relation to the use of
      cigarettes, consume of water, vegetables and place of living. CONCLUSION: The
      different distributions of TE in hair of MS patients compared to controls
      provides an additional indirect evidence of metabolic imbalance of chemical
      elements in the pathogenesis of this disease. The increase in U and decrease in
      Al and Rb levels in MS compared to controls require further assessments as well
      as the observed different distributions of other elements.

PMID- 25856389
TI  - A comparison of genome-wide DNA methylation patterns between different vascular
      tissues from patients with coronary heart disease.
AB  - Epigenetic mechanisms of gene regulation in context of cardiovascular diseases
      are of considerable interest. So far, our current knowledge of the DNA
      methylation profiles for atherosclerosis affected and healthy human vascular
      tissues is still limited. Using the Illumina Infinium Human Methylation27
      BeadChip, we performed a genome-wide analysis of DNA methylation in right
      coronary artery in the area of advanced atherosclerotic plaques, atherosclerotic
      resistant internal mammary arteries, and great saphenous veins obtained from same
      patients with coronary heart disease. The resulting DNA methylation patterns were
      markedly different between all the vascular tissues. The genes hypomethylated in
      athero-prone arteries to compare with atherosclerotic-resistant arteries were
      predominately involved in regulation of inflammation and immune processes, as
      well as development. The great saphenous veins exhibited an increase of the DNA
      methylation age in comparison to the internal mammary arteries. Gene ontology
      analysis for genes harboring hypermethylated CpG-sites in veins revealed the
      enrichment for biological processes associated with the development. Four CpG
      sites located within the MIR10B gene sequence and about 1 kb upstream of the
      HOXD4 gene were also confirmed as hypomethylated in the independent dataset of
      the right coronary arteries in the area of advanced atherosclerotic plaques in
      comparison with the other vascular tissues. The DNA methylation differences
      observed in vascular tissues of patients with coronary heart disease can provide
      new insights into the mechanisms underlying the development of pathology and
      explanation for the difference in graft patency after coronary artery bypass
      grafting surgery. 

PMID- 25856390
TI  - Alexithymia, Suicide Ideation, C-Reactive Protein, and Serum Lipid Levels Among
      Outpatients with Generalized Anxiety Disorder.
AB  - The aim of the present study was to investigate the relationships between
      alexithymia, suicide ideation, C-Reactive Protein (CRP), and serum lipid levels
      in adult outpatients with a DSM-IV diagnosis of Generalized Anxiety Disorder
      (GAD). Seventy consecutive patients with GAD were recruited and evaluated.
      Measures were the Hamilton Anxiety Scale, the Toronto Alexithymia Scale (TAS-20),
      the Scale of Suicide Ideation (SSI), and the Montgomery Asberg Depression Rating
      Scale (MADRS). All patients were assessed for: CRP, high-density lipoprotein
      cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total
      cholesterol (TC), triglyceridaemia (TG), and very-low-density lipoprotein
      cholesterol (VLDL-C). TC/HDL-C and LDL-C/HDL-C ratios were also evaluated.
      Alexithymic patients showed higher scores on almost all rating scales and altered
      serum CRP and lipid levels vs. non-alexithymics. In the hierarchical regression
      model, the presence of higher MADRS scores together with higher scores at the
      Difficulty in Identifying Feelings dimension of TAS-20 were associated with
      higher rates of suicide ideation. Although alexithymic subjects with GAD may show
      a CRP and cholesterol dysregulation, this latter seems independent on increased
      suicide ideation, rather to Difficulty in Identifying Feelings, and subthreshold
      depressive symptoms. Study limitations and future research implications are
      discussed.

PMID- 25856391
TI  - Bayesian LASSO, scale space and decision making in association genetics.
AB  - BACKGROUND: LASSO is a penalized regression method that facilitates model fitting
      in situations where there are as many, or even more explanatory variables than
      observations, and only a few variables are relevant in explaining the data. We
      focus on the Bayesian version of LASSO and consider four problems that need
      special attention: (i) controlling false positives, (ii) multiple comparisons,
      (iii) collinearity among explanatory variables, and (iv) the choice of the tuning
      parameter that controls the amount of shrinkage and the sparsity of the
      estimates. The particular application considered is association genetics, where
      LASSO regression can be used to find links between chromosome locations and
      phenotypic traits in a biological organism. However, the proposed techniques are
      relevant also in other contexts where LASSO is used for variable selection.
      RESULTS: We separate the true associations from false positives using the
      posterior distribution of the effects (regression coefficients) provided by
      Bayesian LASSO. We propose to solve the multiple comparisons problem by using
      simultaneous inference based on the joint posterior distribution of the effects.
      Bayesian LASSO also tends to distribute an effect among collinear variables,
      making detection of an association difficult. We propose to solve this problem by
      considering not only individual effects but also their functionals (i.e. sums and
      differences). Finally, whereas in Bayesian LASSO the tuning parameter is often
      regarded as a random variable, we adopt a scale space view and consider a whole
      range of fixed tuning parameters, instead. The effect estimates and the
      associated inference are considered for all tuning parameters in the selected
      range and the results are visualized with color maps that provide useful insights
      into data and the association problem considered. The methods are illustrated
      using two sets of artificial data and one real data set, all representing typical
      settings in association genetics.

PMID- 25856392
TI  - Financial symmetry and moods in the market.
AB  - This paper studies how certain speculative transitions in financial markets can
      be ascribed to a symmetry break that happens in the collective decision making.
      Investors are assumed to be bounded rational, using a limited set of information
      including past price history and expectation on future dividends. Investment
      strategies are dynamically changed based on realized returns within a game
      theoretical scheme with Nash equilibria. In such a setting, markets behave as
      complex systems whose payoff reflect an intrinsic financial symmetry that
      guarantees equilibrium in price dynamics (fundamentalist state) until the
      symmetry is broken leading to bubble or anti-bubble scenarios (speculative
      state). We model such two-phase transition in a micro-to-macro scheme through a
      Ginzburg-Landau-based power expansion leading to a market temperature parameter
      which modulates the state transitions in the market. Via simulations we prove
      that transitions in the market price dynamics can be phenomenologically explained
      by the number of traders, the number of strategies and amount of information used
      by agents, all included in our market temperature parameter. 

PMID- 25856393
TI  - Community-wide spatial and temporal discordances of seed-seedling shadows in a
      tropical rainforest.
AB  - Several factors decrease plant survival throughout their lifecycles. Among them,
      seed dispersal limitation may play a major role by resulting in highly aggregated
      (contagious) seed and seedling distributions entailing increased mortality. The
      arrival of seeds, furthermore, may not match suitable environments for seed
      survival and, consequently, for seedling establishment. In this study, we
      investigated spatio-temporal patterns of seed and seedling distribution in
      contrasting microhabitats (bamboo and non-bamboo stands) from the Brazilian
      Atlantic Forest. Spatial distribution patterns, spatial concordance between seed
      rain and seedling recruitment between subsequent years in two fruiting seasons
      (2004-2005 and 2007-2009), and the relation between seeds and seedlings with
      environmental factors were examined within a spatially-explicit framework.
      Density and species richness of both seeds and seedlings were randomly
      distributed in non-bamboo stands, but showed significant clustering in bamboo
      stands. Seed and seedling distributions showed across-year inconsistency,
      suggesting a marked spatial decoupling of the seed and seedling stages.
      Generalized linear mixed effects models indicated that only seed density and seed
      species richness differed between stand types while accounting for variation in
      soil characteristics. Our analyses provide evidence of marked recruitment
      limitation as a result of the interplay between biotic and abiotic factors.
      Because bamboo stands promote heterogeneity in the forest, they are important
      components of the landscape. However, at high densities, bamboos may limit
      recruitment for the plant community by imposing marked discordances of seed
      arrival and early seedling recruitment. 

PMID- 25856394
TI  - Quantifying the contribution of statins to the decline in population mean
      cholesterol by socioeconomic group in England 1991 - 2012: a modelling study.
AB  - BACKGROUND: Serum total cholesterol is one of the major targets for
      cardiovascular disease prevention. Statins are effective for cholesterol control
      in individual patients. At the population level, however, their contribution to
      total cholesterol decline remains unclear. The aim of this study was to quantify
      the contribution of statins to the observed fall in population mean cholesterol
      levels in England over the past two decades, and explore any differences between
      socioeconomic groups. METHODS AND FINDINGS: This is a modelling study based on
      data from the Health Survey for England. We analysed changes in observed mean
      total cholesterol levels in the adult England population between 1991-92
      (baseline) and 2011-12. We then compared the observed changes with a
      counterfactual 'no statins' scenario, where the impact of statins on population
      total cholesterol was estimated and removed. We estimated uncertainty intervals
      (UI) using Monte Carlo simulation, where confidence intervals (CI) were
      impractical. In 2011-12, 13.2% (95% CI: 12.5-14.0%) of the English adult
      population used statins at least once per week, compared with 1991-92 when the
      proportion was just 0.5% (95% CI: 0.3-1.0%). Between 1991-92 and 2011-12, mean
      total cholesterol declined from 5.86 mmol/L (95% CI: 5.82-5.90) to 5.17 mmol/L
      (95% CI: 5.14-5.20). For 2011-12, mean total cholesterol was lower in more
      deprived groups. In our 'no statins' scenario we predicted a mean total
      cholesterol of 5.36 mmol/L (95% CI: 5.33-5.40) for 2011-12. Statins were
      responsible for approximately 33.7% (95% UI: 28.9-38.8%) of the total cholesterol
      reduction since 1991-92. The statin contribution to cholesterol reduction was
      greater among the more deprived groups of women, while showing little socio
      economic gradient among men. CONCLUSIONS: Our model suggests that statins
      explained around a third of the substantial falls in total cholesterol observed
      in England since 1991. Approximately two thirds of the cholesterol decrease can
      reasonably be attributed non-pharmacological determinants.

PMID- 25856395
TI  - The anti-inflammatory activity of curcumin protects the genital mucosal
      epithelial barrier from disruption and blocks replication of HIV-1 and HSV-2.
AB  - Inflammation is a known mechanism that facilitates HIV acquisition and the spread
      of infection. In this study, we evaluated whether curcumin, a potent and safe
      anti-inflammatory compound, could be used to abrogate inflammatory processes that
      facilitate HIV-1 acquisition in the female genital tract (FGT) and contribute to
      HIV amplification. Primary, human genital epithelial cells (GECs) were pretreated
      with curcumin and exposed to HIV-1 or HIV glycoprotein 120 (gp120), both of which
      have been shown to disrupt epithelial tight junction proteins, including ZO-1 and
      occludin. Pre-treatment with curcumin prevented disruption of the mucosal barrier
      by maintaining ZO-1 and occludin expression and maintained trans-epithelial
      electric resistance across the genital epithelium. Curcumin pre-treatment also
      abrogated the gp120-mediated upregulation of the proinflammatory cytokines tumor
      necrosis factor-alpha and interleukin (IL)-6, which mediate barrier disruption,
      as well as the chemokines IL-8, RANTES and interferon gamma-induced protein-10
      (IP-10), which are capable of recruiting HIV target cells to the FGT. GECs
      treated with curcumin and exposed to the sexually transmitted co-infecting
      microbes HSV-1, HSV-2 and Neisseria gonorrhoeae were unable to elicit innate
      inflammatory responses that indirectly induced activation of the HIV promoter and
      curcumin blocked Toll-like receptor (TLR)-mediated induction of HIV replication
      in chronically infected T-cells. Finally, curcumin treatment resulted in
      significantly decreased HIV-1 and HSV-2 replication in chronically infected T
      cells and primary GECs, respectively. All together, our results suggest that the
      use of anti-inflammatory compounds such as curcumin may offer a viable
      alternative for the prevention and/or control of HIV replication in the FGT. 

PMID- 25856397
TI  - Unavoidable human errors of tumor size measurement during specimen attachment
      after endoscopic resection: a clinical prospective study.
AB  - OBJECTIVE: Objective evaluation of resected specimen and tumor size is critical
      because the tumor diameter after endoscopic submucosal dissection affects
      therapeutic strategies. In this study, we investigated whether the true tumor
      diameter of gastrointestinal cancer specimens measured by flexible endoscopy is
      subjective by testing whether the specimen is correctly attached to the specimen
      board after endoscopic submucosal dissection resection and whether the size
      differs depending on the endoscopist who attached the specimen. METHODS: Seventy
      two patients diagnosed with early gastric cancer who satisfied the endoscopic
      submucosal dissection expanded-indication guideline were enrolled. Three
      endoscopists were randomly selected before every endoscopic submucosal
      dissection. Each endoscopist separately attached the same resected specimen,
      measured the maximum resection diameter and tumor size, and removed the lesion
      from the attachment board. RESULTS: The resected specimen diameters of the 3
      endoscopists were 44.5 +/- 13.9 mm (95% Confidence Interval (CI): 23-67), 37.4 +/
      12.0 mm (95% CI: 18-60), and 41.1 +/- 13.3 mm (95% CI: 20-63) mm. Comparison
      among 3 groups (Kruskal Wallis H- test), there were significant differences (H =
      6.397, P = 0.040), and recorded tumor sizes were 38.3 +/- 13.1 mm (95% CI: 16
      67), 31.1 +/- 11.2 mm (95% CI: 12.5-53.3), and 34.8 +/- 12.8 (95% CI: 11.5-62.3)
      mm. Comparison among 3 groups, there were significant differences (H = 6.917, P =
      0.031). CONCLUSIONS: Human errors regarding the size of attached resected
      specimens are unavoidable, but it cannot be ignored because it affects the
      patient's additional treatment and/or surgical intervention. We must develop a
      more precise methodology to obtain accurate tumor size. TRIAL REGISTRATION:
      University hospital Medical Information Network UMIN No. 000012915.

PMID- 25856396
TI  - Opposing activity changes in AMP deaminase and AMP-activated protein kinase in
      the hibernating ground squirrel.
AB  - Hibernating animals develop fatty liver when active in summertime and undergo a
      switch to a fat oxidation state in the winter. We hypothesized that this switch
      might be determined by AMP and the dominance of opposing effects: metabolism
      through AMP deaminase (AMPD2) (summer) and activation of AMP-activated protein
      kinase (AMPK) (winter). Liver samples were obtained from 13-lined ground
      squirrels at different times during the year, including summer and multiples
      stages of winter hibernation, and fat synthesis and beta-fatty acid oxidation
      were evaluated. Changes in fat metabolism were correlated with changes in AMPD2
      activity and intrahepatic uric acid (downstream product of AMPD2), as well as
      changes in AMPK and intrahepatic beta-hydroxybutyrate (a marker of fat
      oxidation). Hepatic fat accumulation occurred during the summer with relatively
      increased enzymes associated with fat synthesis (FAS, ACL and ACC) and decreased
      enoyl CoA hydratase (ECH1) and carnitine palmitoyltransferase 1A (CPT1A), rate
      limiting enzymes of fat oxidation. In summer, AMPD2 activity and intrahepatic
      uric acid levels were high and hepatic AMPK activity was low. In contrast, the
      active phosphorylated form of AMPK and beta-hydroxybutyrate both increased during
      winter hibernation. Therefore, changes in AMPD2 and AMPK activity were paralleled
      with changes in fat synthesis and fat oxidation rates during the summer-winter
      cycle. These data illuminate the opposing forces of metabolism of AMP by AMPD2
      and its availability to activate AMPK as a switch that governs fat metabolism in
      the liver of hibernating ground squirrel. 

PMID- 25856398
TI  - A gateway-based system for fast evaluation of protein-protein interactions in
      bacteria.
AB  - Protein-protein interactions are important layers of regulation in all kingdoms
      of life. Identification and characterization of these interactions is one
      challenging task of the post-genomic era and crucial for understanding of
      molecular processes within a cell. Several methods have been successfully
      employed during the past decades to identify protein-protein interactions in
      bacteria, but most of them include tedious and time-consuming manipulations of
      DNA. In contrast, the MultiSite Gateway system is a fast tool for transfer of
      multiple DNA fragments between plasmids enabling simultaneous and site directed
      cloning of up to four fragments into one construct. Here we developed a new set
      of Gateway vectors including custom made entry vectors and modular Destination
      vectors for studying protein-protein interactions via Fluorescence Resonance
      Energy Transfer (FRET), Bacterial two Hybrid (B2H) and split Gaussia luciferase
      (Gluc), as well as for fusions with SNAP-tag and HaloTag for dual-color super
      resolution microscopy. As proof of principle, we characterized the interaction
      between the Salmonella effector SipA and its chaperone InvB via split Gluc and
      B2H approach. The suitability for FRET analysis as well as functionality of
      fusions with SNAP- and HaloTag could be demonstrated by studying the transient
      interaction between chemotaxis response regulator CheY and its phosphatase CheZ. 

PMID- 25856399
TI  - Sharing the space: distribution, habitat segregation and delimitation of a new
      sympatric area of subterranean rodents.
AB  - Subterranean rodents of the genus Ctenomys usually present an allopatric or
      parapatric distribution. Currently, two cases of sympatry have been recognized
      for the genus in the coastal dunes of southern Argentina and southern Brazil. In
      this context, they are ideal models to test hypotheses about the factors that
      delimit the patterns of space use and to understand interspecific interactions in
      small mammals. We investigated the vegetation structure, plant biomass and soil
      hardness selected by two species of subterranean rodents (Ctenomys flamarioni and
      C. minutus) when distributed in sympatry and allopatry from nine different areas
      along the line of coastal dunes in southern Brazil. In addition, our work
      presents a new record of a third area of sympatry for the genus Ctenomys.
      Ctenomys flamarioni and C. minutus show habitat segregation in the area where
      they occur in sympatry. These species show segregation in their selection of
      microhabitats, differing in relation to soil hardness, plant biomass, and plant
      cover. Ctenomys flamarioni showed a distinction in habitat selection when
      occurring in allopatry and sympatry, whereas C. minutus selected the same habitat
      characteristics under both conditions. A possible explanation to the observed
      pattern is that these species have acquired different adaptations over time which
      allows them the ability to exploit different resources and thus avoid competitive
      interactions all together. 

PMID- 25856400
TI  - Correction: Enhanced cellular uptake of albumin-based lyophilisomes when
      functionalized with cell-penetrating peptide TAT in HeLa cells.

PMID- 25856402
TI  - First Detection of a Splice Site beta-Thalassemia Mutation, IVS-I-6 (T > C) (HBB:
      c.92 + 6T > C) in a Chinese Family.
AB  - We present the first description of Chinese individuals with the beta-thalassemia
      (beta-thal) mutation IVS-I-6 (T > C) (HBB: c.92 + 6T > C). This mutation
      interferes with mRNA splicing and results in reducing expression of beta-globin
      chains that leads to a beta(+)-thal phenotype. The beta-globin haplotype anlaysis
      revealed the IVS-I-6 mutation in our case was linked with haplotype VI [- + + - -
      - +] and had Mediterranean characteristics. 

PMID- 25856403
TI  - Dominant effects of first monolayer energetics at donor/acceptor interfaces on
      organic photovoltaics.
AB  - Energy levels of the first monolayer are manipulated at donor/acceptor interfaces
      in planar heterojunction organic photovoltaics by using molecular self
      organization. A "cascade" energy landscape allows thermal-activation-free charge
      generation by photoirradiation, destabilizes the energy of the interfacial charge
      transfer state, and suppresses bimolecular charge recombination, resulting in a
      higher open-circuit voltage and fill factor. 

PMID- 25856401
TI  - Ingestion of a cold temperature/menthol beverage increases outdoor exercise
      performance in a hot, humid environment.
AB  - PURPOSE: A recent laboratory study demonstrated that the ingestion of a
      cold/menthol beverage improved exercise performance in a hot and humid
      environment during 20 km of all-out cycling. Therefore, the aim of this study was
      to determine whether the ingestion of cold water/ice-slurry with menthol would
      improve performance in hot and humid outdoor conditions. METHODS: Ten trained
      males completed three trials of five blocks consisting of 4-km cycling and 1.5-km
      running. During warm-up, every block and recovery, the athletes drank 190 ml of
      aromatized (i.e., with 0.05 mL of menthol) beverage at three temperatures:
      Neutral (ambient temperature) (28.7 degrees C+/-0. 5 degrees C), Cold (3.1
      degrees C+/-0.6 degrees C) or Ice-slurry (0.17 degrees C+/-0.07 degrees C). Trial
      time, core temperature (Tco), heart rate (HR), rate of perceived exertion (RPE),
      thermal sensation (TS) and thermal comfort (TC) were assessed. RESULTS: Ice
      slurry/menthol increased performance by 6.2% and 3.3% compared with neutral
      water/menthol and cold water/menthol, respectively. No between-trial differences
      were noted for Tco, HR, RPE, TC and TS was lower with ice-slurry/menthol and cold
      water/menthol compared with neutral water/menthol. CONCLUSION: A low drink
      temperature combined with menthol lessens the performance decline in hot/humid
      outdoor conditions (i.e., compared with cold water alone). Performances were
      better with no difference in psycho-physiological stress (Tco, HR and RPE)
      between trials. The changes in perceptual parameters caused by absorbing a
      cold/menthol beverage reflect the psychological impact. The mechanism leading to
      these results seems to involve brain integration of signals from physiological
      and psychological sources.

PMID- 25856404
TI  - The Relevance of Directive 2010/53/EU for Living Organ Donation Practice: An
      ELPAT View.
AB  - With the recent transposition of Directive 2010/53/EU into the transplant
      regulation of EU Member States, the time is right to have a closer look at its
      implications for living organ donation practice. We first discuss the relevance
      of the Action Plan which forms the basis for the policy of the European
      Commission in the field of organ donation and transplantation. We then analyze
      the impact of Directive 2010/53/EU which was adopted to support the
      implementation of the Priority Actions set out in the Action Plan. We more
      specifically focus on the obligations of transplant centers engaged in living
      organ donation and highlight their significance for clinical practice. Finally,
      we point out some strengths and weaknesses of the Directive in addressing living
      organ donation. 

PMID- 25856405
TI  - The Critical Role of Induced CD4+ FoxP3+ Regulatory Cells in Suppression of
      Interleukin-17 Production and Attenuation of Mouse Orthotopic Lung Allograft
      Rejection.
AB  - BACKGROUND: Lung transplantation is the only definitive therapy for many forms of
      end-stage lung disease. Studies have demonstrated the critical role of
      interleukin (IL)-17 in the development of lung rejection. Regulatory T cells
      (Tregs) are essential for the establishment and maintenance of immune tolerance.
      METHODS: We established mouse orthotopic lung transplantation models to
      investigate the importance of IL-17 and IL-17-producing cell types in acute lung
      allograft rejection and the efficacy of the adoptive transfer of induced Tregs
      (iTregs) in attenuating pathologic lesions of lung allografts. RESULTS: We found
      that the IL-17 produced by Th17 cells and gammadelta T cells might make the
      primary contributions to the progression of acute lung allograft rejection.
      Interleukin-17 deficiency decreased lung allograft lesions. Exogenous iTregs
      maintained their FoxP3 expression levels in lung allograft recipients. Induced
      Tregs therapy downregulated the expressions of Th17 and IL-17 gammadelta T cells
      and increased IL-10 production in the mouse orthotopic lung transplantation
      models. Moreover, the adoptive transfer of iTregs prolonged the survivals of the
      lung allografts and attenuated the progression of acute rejection. CONCLUSION:
      These data suggested that the adoptive transfer of iTregs could suppress the Th17
      cells and IL-17 gammadelta cells of the recipients, decrease the expression of IL
      17, and attenuate the pathology of acute lung allograft rejection. Exogenous
      iTregs upregulated immunosuppressive factors, such as IL-10 and suppressed IL-17
      producing cells, which was one of the pathways to play a role in protecting lung
      allografts.

PMID- 25856406
TI  - Ischemic Postconditioning of the Liver Graft in Adult Liver Transplantation.
AB  - BACKGROUND: Ischemia-reperfusion (I/R) injury is the main cause of graft failure
      in liver transplantation (LT). Ischemic postconditioning (IPo) has shown to be
      beneficial against I/R injury. Our objective was to compare the results of LT
      with or without IPo. METHODS: One hundred patients undergoing LT alternatively
      received IPo or not. At the time of arterial reperfusion, IPo consisted of three
      1-minute arterial occlusions, interspersed with 1-minute reperfusion pauses. The
      primary endpoint was postoperative aspartate aminotransferase (AST) peak value;
      early graft dysfunction and histological I/R injury were secondary endpoints.
      RESULTS: Median postoperative AST peak values was similar in both groups (426 vs
      463 IU/L, P = 0.21); no difference was found in other postoperative liver
      function tests. In the IPo group, fewer grafts presented severe histological I/R
      injury (12% vs 28%; P = 0.029). Ischemic postconditioning did not induce changes
      in cellular apoptosis but triggered autophagy in periportal areas. Independent
      predictors of severe I/R injury were IPo (odds ratio, 0.20; P = 0.008) and
      arterial warm ischemia duration (odds ratio, 1.05; P = 0.008). Early graft
      dysfunction rate was similar in both groups (20% versus 26%, P = 0.47) and was
      associated with severe histological I/R injury and longer cold ischemia.
      Morbidity, mortality, and 1-year graft and patient survival were similar in both
      groups. CONCLUSIONS: Ischemic postconditioning did not influence postoperative
      AST peak values or other liver function tests. However, our results showed a
      better tolerance to I/R injury on histological findings of grafts receiving IPo.
      Future studies are necessary to optimize the IPo protocol in LT, to clarify its
      clinical impact, and to deepen the molecular understanding.

PMID- 25856407
TI  - Pan-Resistant Achromobacter xylosoxidans and Stenotrophomonas maltophilia
      Infection in Cystic Fibrosis Does Not Reduce Survival After Lung Transplantation.
AB  - BACKGROUND: The number of cystic fibrosis (CF) patients undergoing lung
      transplantation continues to grow, as does the prevalence of multidrug-resistant
      (MDR) gram-negative rods. However, the posttransplant survival of patients with
      MDR pathogens, specifically pan-resistant Achromobacter xylosoxidans and
      Stenotrophomonas maltophilia, is poorly characterized. METHODS: This was a
      retrospective review of CF patients (n = 186; all age, > 16 years) transplanted
      at the University of North Carolina from 1990 through 2013. Respiratory cultures
      before transplantation were reviewed for Achromobacter xylosoxidans and
      Stenotrophomonas maltophilia and their antibiotic susceptibility patterns.
      Bacteria were defined as pan-resistant if they were resistant or intermediate to
      all antibiotics tested; otherwise, organisms were defined as MDR. Patients were
      divided into 5 groups: pan-resistant Achromobacter xylosoxidans (n = 9), MDR
      Achromobacter xylosoxidans (n = 15), pan-resistant Stenotrophomonas maltophilia
      (n = 5), MDR Stenotrophomonas maltophilia (n = 26), and CF patients without
      Achromobacter xylosoxidans, Stenotrophomonas maltophilia or Bulkholderia
      cenocepacia (n = 131). Survival was compared, and cause of death was described.
      RESULTS: The survival was similar between all cohorts (P = 0.29). Recurrence of
      the primary pathogen was the most common with pan-resistant Achromobacter
      xylosoxidans (100%) followed by MDR Stenotrophomonas maltophilia (46%), MDR
      Achromobacter xylosoxidans (33%), and finally, pan-resistant Stenotrophomonas
      maltophilia (20%). Death attributable to the primary pathogen was uncommon,
      occurring in 2 patients with MDR Stenotrophomonas maltophilia and 2 patients with
      MDR Achromobacter xylosoxidans. CONCLUSIONS: The CF patients with Achromobacter
      xylosoxidans and Stenotrophomonas maltophilia have similar posttransplant
      survival as compared to other CF patients, irrespective of their antibiotic
      susceptibility patterns. The presence of these organisms should not preclude lung
      transplantation.

PMID- 25856408
TI  - Murine Fibroblastic Reticular Cells From Lymph Node Interact With CD4+ T Cells
      Through CD40-CD40L.
AB  - BACKGROUND: Costimulatory blockade with anti-CD40L monoclonal antibody (mAb) plus
      donor-specific splenocyte transfusion (DST) induces alloantigen-specific
      tolerance. We previously showed that lymphotoxin signaling in the fibroblastic
      reticular cell (FRC) stromal subset was required for proper lymph node structure
      and function during tolerization in murine cardiac transplantation. Here we
      focused on FRC functions and hypothesized that DST and anti-CD40L mAb-modulated
      FRC interactions with CD4(+) T cells in mice. METHODS: Mice were immunized or
      tolerized by DST or DST plus anti-CD40L mAb. Fibroblastic reticular cells were
      flow-sorted at different timepoints for characterization and in vitro
      proliferation and activation assays. RESULTS: Fibroblastic reticular cells
      responded rapidly to DST by transcribing inflammatory cytokine and chemokine
      messenger RNAs, such as CXCL2, CXCL9, CXCL10, and CCL21. Conversely, anti-CD40L
      mAb inhibited FRC inflammatory responses. CD40 was expressed on FRC and agonistic
      anti-CD40 mAb activated FRC, which supported CD4(+) T-cell proliferation, whereas
      unstimulated FRC did not. Anti-CD3 mAb-activated CD4(+) T cells induced
      inflammatory cytokine and chemokine expressions by FRC, which were inhibited by
      anti-CD40L mAb. Thus, FRC phenotype was altered by interaction with CD4(+) T
      cells through CD40-CD40L, and activated FRC interacted directly with CD4(+) T
      cells to support T cell activation and proliferation in vitro. CONCLUSIONS: Taken
      together, these results demonstrated that CD40 on FRC facilitated bidirectional
      communication between FRC and CD4(+) T cells via CD40-CD40L, thereby altering FRC
      gene expression of immune regulatory molecules. Because blockade of CD40-CD40L
      interactions results in tolerance in mice, identification of FRC-T cell
      interactions provides a new research target for tolerance induction.

PMID- 25856409
TI  - Acute Rejection Clinically Defined Phenotypes Correlate With Long-term Renal
      Allograft Survival.
AB  - BACKGROUND: Classification of acute rejection (AR) based on etiology and timing
      may provide a means for enhancing therapeutic results and allograft survival.
      This study evaluated graft and patient survival after the first AR episodes among
      kidney transplant recipients with an early or late antibody-mediated rejection
      (AMR), acute cellular rejection (ACR) or mixed AR (MAR). METHODS: A prospective
      institutional review board-approved database was queried to identify biopsy
      proven first AR episodes occurring from January 2005 to October 2012. The ACR was
      defined by Banff criteria; borderline AR was excluded. The AMR was defined as 3
      of 4 criteria: renal dysfunction, donor specific antibody, C4d positivity on
      biopsy, and histological changes. The MAR met criteria for both ACR and AMR.
      Early AR occurred within six months post-transplant. AR episodes were then
      assigned to 1 of the 6 categories--early AMR, early ACR, early MAR, late AMR,
      late ACR, and late MAR. RESULTS: One hundred eighty-two kidney transplant
      recipients identified with a first AR episode. Mean follow-up was 773 days (+/-
      715 days). No difference was observed in patient survival. Death-censored graft
      survival was 84%. Death-censored graft loss was higher with late versus early AMR
      (P = 0.01) and late versus early ACR (P = 0.03), but not late versus early MAR (P
      = 0.3). CONCLUSIONS: The AR type demonstrated a hierarchy for graft survival with
      ACR better than MAR better than AMR, which persisted for both early and late AR.
      Improvement in long-term results of AR may require development of specific
      treatment for individual AR types.

PMID- 25856410
TI  - Exploratory movement generates higher-order information that is sufficient for
      accurate perception of scaled egocentric distance.
AB  - Body movement influences the structure of multiple forms of ambient energy,
      including optics and gravito-inertial force. Some researchers have argued that
      egocentric distance is derived from inferential integration of visual and non
      visual stimulation. We suggest that accurate information about egocentric
      distance exists in perceptual stimulation as higher-order patterns that extend
      across optics and inertia. We formalize a pattern that specifies the egocentric
      distance of a stationary object across higher-order relations between optics and
      inertia. This higher-order parameter is created by self-generated movement of the
      perceiver in inertial space relative to the illuminated environment. For this
      reason, we placed minimal restrictions on the exploratory movements of our
      participants. We asked whether humans can detect and use the information
      available in this higher-order pattern. Participants judged whether a virtual
      object was within reach. We manipulated relations between body movement and the
      ambient structure of optics and inertia. Judgments were precise and accurate when
      the higher-order optical-inertial parameter was available. When only optic flow
      was available, judgments were poor. Our results reveal that participants
      perceived egocentric distance from the higher-order, optical-inertial
      consequences of their own exploratory activity. Analysis of participants'
      movement trajectories revealed that self-selected movements were complex, and
      tended to optimize availability of the optical-inertial pattern that specifies
      egocentric distance. We argue that accurate information about egocentric distance
      exists in higher-order patterns of ambient energy, that self-generated movement
      can generate these higher-order patterns, and that these patterns can be detected
      and used to support perception of egocentric distance that is precise and
      accurate. 

PMID- 25856411
TI  - Lung Cancer Screening: Computed Tomography Radiation and Protocols.
AB  - Recent studies have supported the use of low-dose computed tomography (LDCT) of
      the chest as a screening tool for lung cancer. Several professional organizations
      have now included LDCT screening in high-risk populations in their guidelines.
      The United States Preventive Services Task Force has added LDCT to its lung
      cancer-screening guidelines as of December 2013. Recently, the Centers for
      Medicare and Medicaid Services acknowledged that the evidence for LDCT lung
      cancer screening is adequate, provided that eligibility criteria are met. As
      widespread use of LDCT is anticipated, the radiation dose associated with LDCT
      needs to be optimized. The American College of Radiology-Society of Thoracic
      Radiology collaboration and the National Comprehensive Cancer Care Network
      recently provided some guidelines for LDCT utilization for lung cancer screening.
      There are several scanning and image reconstruction techniques that can be used
      for reducing radiation dose in LDCT lung cancer screening. This review article
      presents protocols and guidelines for use of LDCT in lung cancer screening and
      describes our early experience in implementing LDCT at our institution. 

PMID- 25856412
TI  - ACR DIR: A User's Guide for Cardiothoracic Radiologists: Part 2: How to Interpret
      Your DIR Report.
AB  - In the initial installment of this 3-part article, we reviewed the role and
      logistics of the American College of Radiology (ACR) Dose Index Registry (DIR).
      In this second installment, we review the essential components of ACR DIR and
      describe how users can interpret their biannual dose reports by benchmarking them
      against regional or national levels. Understanding these reports can help
      participating institutions to identify specific protocols or practices that may
      benefit from changes in order to minimize patient dose while maintaining
      diagnostic quality examinations. 

PMID- 25856414
TI  - Singlet exciton fission in thin films of tert-butyl-substituted terrylenes.
AB  - Two terrylene chromophores, 2,5,10,13-tetra(tert-butyl)terrylene (1) and 2,5
      di(tert-butyl)terrylene (2), were synthesized and studied to determine their
      singlet exciton fission (SF) efficiencies. Compound 1 crystallizes in one
      dimensional stacks, whereas 2 packs in a slip-stacked, herringbone pattern of
      dimers motif. Strongly quenched fluorescence and rapid singlet exciton decay
      dynamics are observed in vapor-deposited thin films of 1 and 2. Phosphorescence
      measurements on thin films of 1 and 2 show that SF is only 70 meV endoergic for
      these chromophores. Femtosecond transient absorption experiments using low laser
      fluences on these films reveal rapid triplet exciton formation for both 1 (tau =
      120 +/- 10 ps) and 2 (tau = 320 +/- 20 ps) that depends strongly on film
      crystallinity. The transient absorption data are consistent with formation of an
      excimer state prior to SF. Triplet exciton yield measurements indicate nearly
      quantitative SF in thin films of both chromophores in highly crystalline solvent
      vapor-annealed films: 170 +/- 20% for 1 and 200 +/- 30% for 2. These results show
      that significantly different crystal morphologies of the same chromophore can
      both result in high-efficiency SF provided that the energetics are favorable. 

PMID- 25856415
TI  - Occurrence of pesticide residues and transformation products in different types
      of dietary supplements.
AB  - The purpose of this study was to evaluate the presence of pesticide residues and
      transformation products in dietary supplement products. Thirty-two samples were
      analysed to determine 177 pesticides by gas chromatography-tandem mass
      spectrometry (GC-MS/MS) and 333 pesticides by liquid chromatography-high
      resolution mass spectrometry (LC-HRMS). Pesticides were extracted from different
      kinds of dietary supplements by the use of a modified QuEChERS extraction method.
      Six samples contained pesticide residues at concentration up to 92.7 ug kg(-1),
      but only butralin exceeded the maximum residue limits set for raw material. In
      addition to target compounds, LC-HRMS enables the simultaneous detection of non
      target pesticides. In this case, transformation products of pesticides were
      detected in the analysed samples using HRMS analyser (Exactive-Orbitrap). These
      compounds were not included in the original method, and they were monitored as
      post-target compounds, knowing their molecular formula and exact mass. Mass
      accuracy was always < 2 ppm, corresponding to a maximum mass error. The positive
      findings endorse the idea that a deeper and continuous investigation of pesticide
      residues and transformation products in dietary supplement products is necessary
      in order to guaranty consumer's safety. 

PMID- 25856416
TI  - Palladium-catalyzed, ligand-free Suzuki reaction in water using aryl
      fluorosulfates.
AB  - Aryl fluorosulfates were prepared by a simple method and employed as coupling
      partners in the Suzuki-Miyaura reaction. The cross-coupling reactions were
      performed in water under air at room temperature without ligands or additives
      such as surfactants or phase-transfer reagents and proceeded smoothly to give
      excellent yields. Aryl fluorosulfates could also be used as alternatives to
      halides or triflates in other coupling reactions. 

PMID- 25856413
TI  - Transient activation of microglia following acute alcohol exposure in developing
      mouse neocortex is primarily driven by BAX-dependent neurodegeneration.
AB  - Fetal alcohol exposure is the most common known cause of preventable mental
      retardation, yet we know little about how microglia respond to, or are affected
      by, alcohol in the developing brain in vivo. Using an acute (single day) model of
      moderate (3 g/kg) to severe (5 g/kg) alcohol exposure in postnatal day (P) 7 or
      P8 mice, we found that alcohol-induced neuroapoptosis in the neocortex is closely
      correlated in space and time with the appearance of activated microglia near dead
      cells. The timing and molecular pattern of microglial activation varied with the
      level of cell death. Although microglia rapidly mobilized to contact and engulf
      late-stage apoptotic neurons, apoptotic bodies temporarily accumulated in
      neocortex, suggesting that in severe cases of alcohol toxicity the
      neurodegeneration rate exceeds the clearance capacity of endogenous microglia.
      Nevertheless, most dead cells were cleared and microglia began to deactivate
      within 1-2 days of the initial insult. Coincident with microglial activation and
      deactivation, there was a transient increase in expression of pro-inflammatory
      factors, TNFalpha and IL-1beta, after severe (5 g/kg) but not moderate (3 g/kg)
      EtOH levels. Alcohol-induced microglial activation and pro-inflammatory factor
      expression were largely abolished in BAX null mice lacking neuroapoptosis,
      indicating that microglial activation is primarily triggered by apoptosis rather
      than the alcohol. Therefore, acute alcohol exposure in the developing neocortex
      causes transient microglial activation and mobilization, promoting clearance of
      dead cells and tissue recovery. Moreover, cortical microglia show a remarkable
      capacity to rapidly deactivate following even severe neurodegenerative insults in
      the developing brain.

PMID- 25856417
TI  - Stereochemistry of spiro-acetalized [60]fullerenes: how the exo and endo
      stereoisomers influence organic solar cell performance.
AB  - Exploiting bis-addition products of fullerenes is a rational way to improve the
      efficiency of bulk heterojunction-type organic photovoltaic cells (OPV); however,
      this design inherently produces regio- and stereoisomers that may impair the
      ultimate performance and fabrication reproducibility. Here, we report
      unprecedented exo and endo stereoisomers of the spiro-acetalized [60]fullerene
      monoadduct with methyl- or phenyl-substituted 1,3-dioxane (SAF6). Although there
      is no chiral carbon in either the reagent or the fullerene, equatorial (eq)
      rather than axial (ax) isomers are selectively produced at an exo-eq:endo-eq
      ratio of approximately 1:1 and can be easily separated using silica gel column
      chromatography. Nuclear Overhauser effect measurements identified the
      conformations of the straight exo isomer and bent endo isomer. We discuss the
      origin of stereoselectivity, the anomeric effect, intermolecular ordering in the
      film state, and the performance of poly(3-hexylthiophene):substituted SAF6 OPV
      devices. Despite their identical optical and electrochemical properties, their
      solubilities and space-charge limited current mobilities are largely influenced
      by the stereoisomers, which leads to variation in the OPV efficiency. This study
      emphasizes the importance of fullerene stereochemistry for understanding the
      relationship between stereochemical structures and device output. 

PMID- 25856418
TI  - The impending epidemic of chronic cardiopulmonary disease and multimorbidity: the
      need for new research approaches to guide daily practice.
AB  - Mortality caused by acute cardiopulmonary disease is decreasing, and in many
      countries the population is aging rapidly. Yet, the life-years gained are often
      spent with multiple chronic and slowly progressive conditions, and this
      particularly applies to patients with cardiopulmonary disease. Affected
      individuals often have multiple diagnoses related to the cardiopulmonary
      metabolic axis with accelerated aging and gradually progressive failure of organs
      that provide the body with oxygen and nutrients. This more or less reflects an
      "engine running out of fuel." This, for instance, is the case with the concurrent
      presence of COPD and heart failure in one patient that is often combined with
      other comorbidities such as atrial fibrillation, renal failure, or diabetes. This
      asks for a paradigm shift: away from single-disease-oriented patient management
      and toward patient-tailored multimorbidity medicine. Daily clinical practice is
      already recognizing this on a daily basis, yet clinical research and guidelines
      are still lagging behind. Thus, novel research approaches are needed to better
      guide evidence-based clinical practice. These approaches include the construction
      of diagnostic models to predict the presence of multiple diseases simultaneously,
      individual patient data meta-analysis as a method to examine variation in the
      effects of treatments or diagnostic tests depending on comorbidity, and the
      construction of therapeutic prediction models that predict the therapeutic effect
      of drugs based on the presence (or absence) of relevant comorbidity. We argue
      that multimorbidity should be regarded as a "friend" and not as a "foe" in
      clinical research addressing the current clinical problems in daily practice. 

PMID- 25856419
TI  - Validity of home blood pressure measurements manually registered by patients
      after an educational session provided by community pharmacists.
AB  - When home blood pressure (HBP) measurements are taken, the readings can be
      registered manually by the patient and/or stored in the device's memory. The
      instructions provided by healthcare professionals would be particularly relevant
      to guarantee the reliability of manual blood pressure (BP) figures and enhance
      clinical decision making. The aim of this study is assess the agreement between
      HBP measurements manually registered by patients and those stored in the device's
      memory after an educational session provided by community pharmacists. Secondary
      data of the MEPAFAR and the Palmera studies have been used in this analysis. All
      the (treated hypertensive) patients attended an individual educational session in
      which they were instructed on how to use the measurement device and properly
      measure and manually register HBP. The same device and HBP monitoring protocol
      were used in both studies: 4 consecutive days (three morning measurements and
      three in the evening). HBP measurements were both manually registered by patients
      and stored in the device's memory. To evaluate the agreement between BP figures,
      Lin's correlation-concordance coefficient and kappa coefficient were used for
      quantitative and qualitative agreement, respectively. One hundred and sixty-sixty
      patients were included in this analysis. The agreement between the average manual
      and the stored HBP was very good [systolic=0.99, 95% confidence interval (CI):
      0.99-0.99; diastolic=0.99, 95% CI: 0.99-1.00]. 99.4% of patients were classified
      in the same category by both alternatives [kappa index=0.99 (95% CI: 0.98-1.00)].
      In this sample of treated hypertensive patients, the agreement between manually
      registered and stored BP figures was very good. This high concordance may be
      explained by the pharmacist's intervention. 

PMID- 25856420
TI  - Reliability of home blood pressure monitoring: in the context of validation and
      accuracy.
AB  - OBJECTIVE: Home blood pressure (BP) monitoring offers clinically relevant
      information enriched with more abundant data. However, there are few studies
      addressing the reliability of home BP devices and the quality of its data. This
      study aimed to evaluate the current status of home BP devices in terms of
      validation and accuracy. PARTICIPANTS AND METHODS: Hypertensive patients with
      automated upper arm-type BP devices were consecutively enrolled. First, the
      validation status of each device was assessed through the website. Next, the
      accuracy of the individual device was evaluated by comparing the mean BP values
      between the automated device and a mercury sphygmomanometer. Accuracy of the
      device was defined as having less than a 5 mmHg difference in the mean BP values.
      RESULTS: A total of 212 individuals were analyzed; 38.7% (82 of 212) of the
      participants used validated devices and 85.4% (181 of 212) were accurate.
      Inaccuracy was more common with nonvalidated devices than validated devices
      [19.2% (n=25) vs. 7.3% (n=6), P=0.017]. The range of inaccuracy of the validated
      devices was 6-26 mmHg for the systolic BP and 6-11 mmHg for the diastolic BP.
      CONCLUSION: The present study showed that nonvalidated devices are used widely in
      clinical practice and a substantial portion is inaccurate. Therefore,
      recommendation of validated devices should be the first step. Furthermore, all
      devices need to be examined for accuracy before use irrespective of their
      validation status.

PMID- 25856421
TI  - Blood pressure and heart rate responses in volunteer firefighters while wearing
      personal protective equipment.
AB  - BACKGROUND: Hypertension, cardiovascular disease, and obesity are global health
      problems and are a large concern for firefighters. The leading cause of death
      among firefighters is cardiac-related; hence, it is important to understand how
      firefighter personal protective equipment (PPE) affects cardiovascular responses
      to different activities. Volunteer firefighters represent 70% of all firefighters
      and are an understudied population. To the best of our knowledge, this is the
      first study to report blood pressure (BP) responses in volunteer firefighters.
      METHODS AND RESULTS: Thirty-six male, nonsmoking volunteer firefighters (27.8+/
      9.7 years) underwent two maximal treadmill tests within 2 weeks, one in regular
      gym clothes and one in PPE. We found that while wearing PPE, which weighs 54.2+/
      3.5 lbs, BP responses are exaggerated during work and in recovery. Systolic BP
      and heart rate were significantly (P<0.05) higher at each submaximal stage and
      during active recovery of the PPE test compared with the regular clothing test
      (15-23 mmHg and 20-34 bpm higher, respectively). Test time and VO2 max were lower
      in the PPE test (P<0.05). CONCLUSION: BP responses are exaggerated while wearing
      full fire protective gear and remain elevated during recovery. Awareness of how
      firefighting activities affect BP is important; so future studies should examine
      how the BP increase relates to resting BP levels, to PPE weight, and to the
      thermal effects of the PPE.

PMID- 25856422
TI  - Targeting metabolic disturbance in the diabetic heart.
AB  - Diabetic cardiomyopathy is defined as ventricular dysfunction initiated by
      alterations in cardiac energy substrates in the absence of coronary artery
      disease and hypertension. In addition to the demonstrated burden of
      cardiovascular events associated with diabetes, diabetic cardiomyopathy partly
      explains why diabetic patients are subject to a greater risk of heart failure and
      a worse outcome after myocardial ischemia. The raising prevalence and
      accumulating costs of cardiovascular disease in diabetic patients underscore the
      deficiencies of tertiary prevention and call for a shift in medical treatment. It
      is becoming increasingly clearer that the effective prevention and treatment of
      diabetic cardiomyopathy require measures to regulate the metabolic derangement
      occurring in the heart rather than merely restoring suitable systemic parameters.
      Recent research has provided deeper insight into the metabolic etiology of
      diabetic cardiomyopathy and numerous heart-specific targets that may substitute
      or reinforce current strategies. From both experimental and translational
      perspectives, in this review we first discuss the progress made with conventional
      therapies, and then focus on the need for prospective metabolic targets that may
      avert myocardial vulnerability and functional decline in next-generation diabetic
      care. 

PMID- 25856424
TI  - Bone marrow transplant for X-linked protoporphyria with severe hepatic fibrosis.
AB  - XLP is an erythroid porphyria that results in variable cutaneous photosensitivity
      due to accumulation of protoporphyrin. The genetic defect in XLP is mutation of
      the gene ALAS2, resulting in gain of function for the erythroid enzyme 5
      aminolevulinate synthase 2. Previous reports have shown that protoporphyrin
      induced liver disease may also occur in XLP, occasionally severe enough to
      warrant liver transplantation; however, transplantation may be followed by injury
      to the graft due to continued presence of the underlying metabolic disorder in
      the bone marrow. We present a case of XLP with severe liver disease successfully
      treated with HPCT to avoid liver transplantation. The case also demonstrates the
      feasibility of reduced intensity transplant to provide engraftment sufficient for
      correction of porphyria and tolerability of reduced intensity conditioning
      containing TLI in the face of severe liver injury. 

PMID- 25856423
TI  - Down regulation of NO signaling in Trypanosoma cruzi upon parasite-extracellular
      matrix interaction: changes in protein modification by nitrosylation and
      nitration.
AB  - BACKGROUND: Adhesion of the Trypanosoma cruzi trypomastigotes, the causative
      agent of Chagas' disease in humans, to components of the extracellular matrix
      (ECM) is an important step in host cell invasion. The signaling events triggered
      in the parasite upon binding to ECM are less explored and, to our knowledge,
      there is no data available regarding *NO signaling. METHODOLOGY/PRINCIPAL
      FINDINGS: Trypomastigotes were incubated with ECM for different periods of time.
      Nitrated and S-nitrosylated proteins were analyzed by Western blotting using anti
      nitrotyrosine and S-nitrosyl cysteine antibodies. At 2 h incubation time, a
      decrease in NO synthase activity, *NO, citrulline, arginine and cGMP
      concentrations, as well as the protein modifications levels have been observed in
      the parasite. The modified proteins were enriched by immunoprecipitation with
      anti-nitrotyrosine antibodies (nitrated proteins) or by the biotin switch method
      (S-nitrosylated proteins) and identified by MS/MS. The presence of both
      modifications was confirmed in proteins of interest by immunoblotting or
      immunoprecipitation. CONCLUSIONS/SIGNIFICANCE: For the first time it was shown
      that T. cruzi proteins are amenable to modifications by S-nitrosylation and
      nitration. When T. cruzi trypomastigotes are incubated with the extracellular
      matrix there is a general down regulation of these reactions, including a
      decrease in both NOS activity and cGMP concentration. Notwithstanding, some
      specific proteins, such as enolase or histones had, at least, their nitration
      levels increased. This suggests that post-translational modifications of T. cruzi
      proteins are not only a reflex of NOS activity, implying other mechanisms that
      circumvent a relatively low synthesis of *NO. In conclusion, the extracellular
      matrix, a cell surrounding layer of macromolecules that have to be trespassed by
      the parasite in order to be internalized into host cells, contributes to the
      modification of *NO signaling in the parasite, probably an essential move for the
      ensuing invasion step.

PMID- 25856427
TI  - Measurement of a Comprehensive Sex Steroid Profile in Rodent Serum by High
      Sensitive Gas Chromatography-Tandem Mass Spectrometry.
AB  - Accurate measurement of sex steroid concentrations in rodent serum is essential
      to evaluate mouse and rat models for sex steroid-related disorders. The aim of
      the present study was to develop a sensitive and specific gas chromatography
      tandem mass spectrometry (GC-MS/MS) method to assess a comprehensive sex steroid
      profile in rodent serum. A major effort was invested in reaching an exceptionally
      high sensitivity for measuring serum estradiol concentrations. We established a
      GC-MS/MS assay with a lower limit of detection for estradiol, estrone, T, DHT,
      progesterone, androstenedione, and dehydroepiandrosterone of 0.3, 0.5, 4.0, 1.6,
      8, 4.0, and 50 pg/mL, respectively, whereas the corresponding values for the
      lower limit of quantification were 0.5, 0.5, 8, 2.5, 74, 12, and 400 pg/mL,
      respectively. Calibration curves were linear, intra- and interassay coefficients
      of variation were low, and accuracy was excellent for all analytes. The
      established assay was used to accurately measure a comprehensive sex steroid
      profile in female rats and mice according to estrous cycle phase. In addition, we
      characterized the impact of age, sex, gonadectomy, and estradiol treatment on
      serum concentrations of these sex hormones in mice. In conclusion, we have
      established a highly sensitive and specific GC-MS/MS method to assess a
      comprehensive sex steroid profile in rodent serum in a single run. This GC-MS/MS
      assay has, to the best of our knowledge, the best detectability reported for
      estradiol. Our method therefore represents an ideal tool to characterize sex
      steroid metabolism in a variety of sex steroid-related rodent models and in human
      samples with low estradiol levels. 

PMID- 25856425
TI  - Quantum dots-based quantitative and in situ multiple imaging on ki67 and
      cytokeratin to improve ki67 assessment in breast cancer.
AB  - BACKGROUND: As a marker for tumor cell proliferation, Ki67 has important impacts
      on breast cancer (BC) prognosis. Although immunohistochemical staining is the
      current standard method, variations in analytical practice make it difficult for
      pathologists to manually measure Ki67 index. This study was to develop a
      fluorescent spectrum-based quantitative analysis of Ki67 expression by quantum
      dots (QDs) multiple imaging technique. METHODS: A QDs-based in situ multiple
      fluorescent imaging method was developed, which stained nuclear Ki67 as red
      signal and cytoplasmic cytokeratin (CK) as green signal. Both Ki67 and CK signals
      were automatically separated and quantified by professional spectrum analysis
      software. This technique was applied to tissue microarrays from 240 BC patients.
      Both Ki67 and CK values, and Ki67/CK ratio were obtained for each patient, and
      their prognostic value on 5-year disease free survival was assessed. RESULTS:
      This method simultaneously stains nuclear Ki67 and cytoplasmic CK with clear
      signal contrast, making it easy for signal separation and quantification. The
      total fluorescent signal intensities of both Ki67 sum and CK sum were obtained,
      and Ki67/CK ratio calculated. Ki67 sum and Ki67/CK ratio were each attributed
      into two grades by X-tile software based on the best P value principle.
      Multivariate analysis showed Ki67 grade (P = 0.047) and Ki67/CK grade (P = 0.004)
      were independent prognostic factors. Furthermore, area under curve (AUC) of ROC
      analysis for Ki67/CK grade (AUC: 0.683, 95%CI: 0.613-0.752) was higher than Ki67
      grade (AUC: 0.665, 95%CI: 0.596-0.734) and HER-2 gene (AUC: 0.586, 95%CI: 0.510
      0.661), but lower than N stage (AUC: 0.760, 95%CI: 0.696-0.823) and histological
      grade (AUC: 0.756, 95%CI: 0.692-0.820) on predicting the risk for recurrence.
      CONCLUSIONS: A QDs-based quantitative and in situ multiple imaging on Ki67 and CK
      was developed to improve Ki67 assessment in BC, and Ki67/CK grade had better
      performance than Ki67 grade in predicting prognosis.

PMID- 25856428
TI  - Blockage of the Neonatal Leptin Surge Affects the Gene Expression of Growth
      Factors, Glial Proteins, and Neuropeptides Involved in the Control of Metabolism
      and Reproduction in Peripubertal Male and Female Rats.
AB  - Leptin (Lep) is important in the development of neuroendocrine circuits involved
      in metabolic control. Because both Lep and metabolism influence pubertal
      development, we hypothesized that early changes in Lep signaling could also
      modulate hypothalamic (HT) systems involved in reproduction. We previously
      demonstrated that a single injection of a Lep antagonist (Antag) on postnatal day
      (PND)9, coincident with the neonatal Lep peak, induced sexually dimorphic
      modifications in trophic factors and markers of cell turnover and neuronal
      maturation in the HT on PND13. Here, our aim was to investigate whether the
      alterations induced by Lep antagonism persist into puberty. Accordingly, male and
      female rats were treated with a pegylated super Lep Antag from PND5 to PND9 and
      killed just before the normal appearance of external signs of puberty (PND33 in
      females and PND43 in males). There was no effect on body weight, but in males
      food intake increased, subcutaneous adipose tissue decreased and HT neuropeptide
      Y and Agouti-related peptide mRNA levels were reduced, with no effect in females.
      In both sexes, the Antag increased HT mRNA levels of the kisspeptin receptor, G
      protein-coupled recepter 54 (Gpr54). Expression of the Lep receptor, trophic
      factors, and glial markers were differently affected in the HT of peripubertal
      males and females. Lep production in adipose tissue was decreased in Antag
      treated rats of both sexes, with production of other cytokines being
      differentially regulated between sexes. In conclusion, in addition to the long
      term effects on metabolism, changes in neonatal Lep levels modifies factors
      involved in reproduction that could possibly affect sexual maturation. 

PMID- 25856426
TI  - Direct binding of ledipasvir to HCV NS5A: mechanism of resistance to an HCV
      antiviral agent.
AB  - Ledipasvir, a direct acting antiviral agent (DAA) targeting the Hepatitis C Virus
      NS5A protein, exhibits picomolar activity in replicon cells. While its mechanism
      of action is unclear, mutations that confer resistance to ledipasvir in HCV
      replicon cells are located in NS5A, suggesting that NS5A is the direct target of
      ledipasvir. To date co-precipitation and cross-linking experiments in replicon or
      NS5A transfected cells have not conclusively shown a direct, specific interaction
      between NS5A and ledipasvir. Using recombinant, full length NS5A, we show that
      ledipasvir binds directly, with high affinity and specificity, to NS5A.
      Ledipasvir binding to recombinant NS5A is saturable with a dissociation constant
      in the low nanomolar range. A mutant form of NS5A (Y93H) that confers resistance
      to ledipasvir shows diminished binding to ledipasvir. The current study shows
      that ledipasvir inhibits NS5A through direct binding and that resistance to
      ledipasvir is the result of a reduction in binding affinity to NS5A mutants. 

PMID- 25856430
TI  - Conditional Viral Tract Tracing Delineates the Projections of the Distinct
      Kisspeptin Neuron Populations to Gonadotropin-Releasing Hormone (GnRH) Neurons in
      the Mouse.
AB  - Kisspeptin neurons play an essential role in the regulation of fertility through
      direct regulation of the GnRH neurons. However, the relative contributions of the
      two functionally distinct kisspeptin neuron subpopulations to this critical
      regulation are not fully understood. Here we analyzed the specific projection
      patterns of kisspeptin neurons originating from either the rostral
      periventricular nucleus of the third ventricle (RP3V) or the arcuate nucleus
      (ARN) using a cell-specific, viral-mediated tract-tracing approach. We
      stereotaxically injected a Cre-dependent recombinant adenovirus encoding
      farnesylated enhanced green fluorescent protein into the ARN or RP3V of adult
      male and female mice expressing Cre recombinase in kisspeptin neurons. Fibers
      from ARN kisspeptin neurons projected widely; however, we did not find any
      evidence for direct contact with GnRH neuron somata or proximal dendrites in
      either sex. In contrast, we identified RP3V kisspeptin fibers in close contact
      with GnRH neuron somata and dendrites in both sexes. Fibers originating from both
      the RP3V and ARN were observed in close contact with distal GnRH neuron processes
      in the ARN and in the lateral and internal aspects of the median eminence.
      Furthermore, GnRH nerve terminals were found in close contact with the proximal
      dendrites of ARN kisspeptin neurons in the ARN, and ARN kisspeptin fibers were
      found contacting RP3V kisspeptin neurons in both sexes. Together these data
      delineate selective zones of kisspeptin neuron inputs to GnRH neurons and
      demonstrate complex interconnections between the distinct kisspeptin populations
      and GnRH neurons. 

PMID- 25856429
TI  - Substance p regulates puberty onset and fertility in the female mouse.
AB  - Puberty is a tightly regulated process that leads to reproductive capacity. Kiss1
      neurons are crucial in this process by stimulating GnRH, yet how Kiss1 neurons
      are regulated remains unknown. Substance P (SP), an important neuropeptide in
      pain perception, induces gonadotropin release in adult mice in a kisspeptin
      dependent manner. Here, we assessed whether SP, through binding to its receptor
      NK1R (neurokinin 1 receptor), participates in the timing of puberty onset and
      fertility in the mouse. We observed that 1) selective NK1R agonists induce
      gonadotropin release in prepubertal females; 2) the expression of Tac1 (encoding
      SP) and Tacr1 (NK1R) in the arcuate nucleus is maximal before puberty, suggesting
      increased SP tone; 3) repeated exposure to NK1R agonists prepubertally advances
      puberty onset; and 4) female Tac1(-/-) mice display delayed puberty; moreover, 5)
      SP deficiency leads to subfertility in females, showing fewer corpora lutea and
      antral follicles and leading to decreased litter size. Thus, our findings support
      a role for SP in the stimulation of gonadotropins before puberty, acting via
      Kiss1 neurons to stimulate GnRH release, and its involvement in the attainment of
      full reproductive capabilities in female mice. 

PMID- 25856431
TI  - Does the arthropod microbiota impact the establishment of vector-borne diseases
      in mammalian hosts?
AB  - The impact of the microbiota on the immune status of its host is a source of
      intense research and publicity. In comparison, the effect of arthropod microbiota
      on vector-borne infectious diseases has received little attention. A better
      understanding of the vector microbiota in relation to mammalian host immune
      responses is vital, as it can lead to strategies that affect transmission and
      improve vaccine design in a field of research where few vaccines exist and
      effective treatment is rare. Recent demonstrations of how microbiota decrease
      pathogen development in arthropods, and thus alter vector permissiveness to
      vector-borne diseases (VBDs), have led to renewed interest. However, hypotheses
      on the interactions between the arthropod-derived microbiota and the mammalian
      hosts have yet to be addressed. Advances in DNA sequencing technology, increased
      yield and falling costs, mean that these studies are now feasible for many
      microbiologists and entomologists. Here, we distill current knowledge and put
      forward key questions and experimental designs to shed light on this burgeoning
      research topic. 

PMID- 25856434
TI  - Mining the modular structure of protein interaction networks.
AB  - BACKGROUND: Cluster-based descriptions of biological networks have received much
      attention in recent years fostered by accumulated evidence of the existence of
      meaningful correlations between topological network clusters and biological
      functional modules. Several well-performing clustering algorithms exist to infer
      topological network partitions. However, due to respective technical
      idiosyncrasies they might produce dissimilar modular decompositions of a given
      network. In this contribution, we aimed to analyze how alternative modular
      descriptions could condition the outcome of follow-up network biology analysis.
      METHODOLOGY: We considered a human protein interaction network and two
      paradigmatic cluster recognition algorithms, namely: the Clauset-Newman-Moore and
      the infomap procedures. We analyzed to what extent both methodologies yielded
      different results in terms of granularity and biological congruency. In addition,
      taking into account Guimera's cartographic role characterization of network
      nodes, we explored how the adoption of a given clustering methodology impinged on
      the ability to highlight relevant network meso-scale connectivity patterns.
      RESULTS: As a case study we considered a set of aging related proteins and showed
      that only the high-resolution modular description provided by infomap, could
      unveil statistically significant associations between them and inter/intra
      modular cartographic features. Besides reporting novel biological insights that
      could be gained from the discovered associations, our contribution warns against
      possible technical concerns that might affect the tools used to mine for
      interaction patterns in network biology studies. In particular our results
      suggested that sub-optimal partitions from the strict point of view of their
      modularity levels might still be worth being analyzed when meso-scale features
      were to be explored in connection with external source of biological knowledge.

PMID- 25856436
TI  - Antitumor Properties of the leaf essential oil of Zornia brasiliensis.
AB  - Zornia brasiliensis, popularly known as "urinaria", "urinana", and "carrapicho",
      is a medicinal plant used in Brazilian northeast folk medicine as a diuretic and
      against venereal diseases. The aim of this study was to investigate the chemical
      composition and antitumor potential of the leaf essential oil of Z. brasiliensis.
      The essential oil was obtained by hydrodistillation using a Clevenger-type
      apparatus and analyzed by GC-MS and GC-FID. Its composition was characterized by
      the presence of trans-nerolidol, germacrene D, trans-caryophyllene, alpha
      humulene, and farnesene as major constituents. In vitro cytotoxicity of the
      essential oil and some of its major constituents (trans-nerolidol, trans
      caryophyllene, and alpha-humulene) was evaluated for tumor cell lines from
      different histotypes using the Alamar blue assay. The essential oil, but not the
      constituents tested, presented promising cytotoxicity. Furthermore, mice
      inoculated with B16-F10 mouse melanoma were used to confirm its in vivo
      effectiveness. An in vivo antitumor study showed tumor growth inhibition rates of
      1.68-38.61 % (50 and 100 mg/kg, respectively). In conclusion, the leaf essential
      oil of Z. brasiliensis presents trans-nerolidol, germacrene D, trans
      caryophyllene, alpha-humulene, and farnesene as major constituents and is able to
      inhibit cell proliferation in cultures as well as in tumor growth in mice. 

PMID- 25856432
TI  - Transcriptome markers of viral persistence in naturally-infected andes virus
      (bunyaviridae) seropositive long-tailed pygmy rice rats.
AB  - Long-tailed pygmy rice rats (Oligoryzomys longicaudatus) are principal reservoir
      hosts of Andes virus (ANDV) (Bunyaviridae), which causes most hantavirus
      cardiopulmonary syndrome cases in the Americas. To develop tools for the study of
      the ANDV-host interactions, we used RNA-Seq to generate a de novo transcriptome
      assembly. Splenic RNA from five rice rats captured in Chile, three of which were
      ANDV-infected, was used to generate an assembly of 66,173 annotated transcripts,
      including noncoding RNAs. Phylogenetic analysis of selected predicted proteins
      showed similarities to those of the North American deer mouse (Peromyscus
      maniculatus), the principal reservoir of Sin Nombre virus (SNV). One of the
      infected rice rats had about 50-fold more viral burden than the others,
      suggesting acute infection, whereas the remaining two had levels consistent with
      persistence. Differential expression analysis revealed distinct signatures among
      the infected rodents. The differences could be due to 1) variations in viral
      load, 2) dimorphic or reproductive differences in splenic homing of immune cells,
      or 3) factors of unknown etiology. In the two persistently infected rice rats,
      suppression of the JAK-STAT pathway at Stat5b and Ccnot1, elevation of Casp1, RIG
      I pathway factors Ppp1cc and Mff, and increased FC receptor-like transcripts
      occurred. Caspase-1 and Stat5b activation pathways have been shown to stimulate T
      helper follicular cell (TFH) development in other species. These data are also
      consistent with reports suggestive of TFH stimulation in deer mice experimentally
      infected with hantaviruses. In the remaining acutely infected rice rat, the
      apoptotic pathway marker Cox6a1 was elevated, and putative anti-viral factors
      Abcb1a, Fam46c, Spp1, Rxra, Rxrb, Trmp2 and Trim58 were modulated. Transcripts
      for preproenkephalin (Prenk) were reduced, which may be predictive of an
      increased T cell activation threshold. Taken together, this transcriptome dataset
      will permit rigorous examination of rice rat-ANDV interactions and may lead to
      better understanding of virus ecology. 

PMID- 25856437
TI  - Revealing Medicinal Plants That Are Useful for the Comprehensive Management of
      Epilepsy and Associated Comorbidities through In Silico Mining of Their
      Phytochemical Diversity.
AB  - In silico techniques in drug discovery may rationalise and speed up the
      identification of lead molecules from nature. Drug discovery from medicinal
      plants has mostly been confined to indications in accordance with their ethnical
      use only. However, the availability of multiple phytoconstituents in medicinal
      plants suggests that these may be much more useful beyond their traditional uses
      and in the management of chronic diseases, along with their comorbidities. In
      this study, the computer programmes PASS and PharmaExpert were used to reveal the
      medicinal plants useful in the comprehensive management of epilepsy and
      associated psychiatric disorders based on the pleiotropic effects predicted for
      their phytoconstituents. In silico analysis revealed that seven of 50 medicinal
      plants from traditional Indian medicine possessed the desired pleiotropic effect,
      i.e., anticonvulsant, antidepressant, and nootropic activities. The majority of
      phytoconstituents from Passiflora incarnata were concurrently predicted to have
      the desired pleiotropic effects. Therefore, P. incarnata was pharmacologically
      validated using the pentylenetetrazole kindling mouse model. Behavioural and
      neurochemical evaluations confirmed the ameliorative role of P. incarnata in
      epilepsy and the associated depression and memory deficit. The pharmacological
      findings from this study propose that PASS and PharmaExpert may serve as good
      tools for the optimisation of the selection of plants based on their
      phytoconstituents for the treatment of different ailments, even beyond their
      traditional use. 

PMID- 25856433
TI  - Small peptide inhibitor of JNK3 protects dopaminergic neurons from MPTP induced
      injury via inhibiting the ASK1-JNK3 signaling pathway.
AB  - INTRODUCTION AND AIMS: The ASK1-JNK3 signaling pathway plays a pivotal role in
      the pathogenesis of Parkinson's disease (PD). The specific binding of beta
      arrestin2 to JNK3 is essential for activation of the ASK1-JNK3 cascade,
      representing a potential therapeutic target for preventing dopaminergic neuronal
      death in PD. The aim of this study was to identify a novel strategy for the
      prevention of dopaminergic neuronal death in PD. METHODS: Based on the specific
      binding of beta-arrestin2 to JNK3, a 21-amino-acid fusion peptide, termed JNK3-N
      Tat, was synthesized. We evaluated the ability of this peptide to inhibit the
      binding of beta-arrestin2 to its target domain in JNK3 in vitro and in vivo.
      RESULTS: The JNK3-N-Tat peptide inhibited activation of the ASK1-JNK3 cascade by
      disrupting the interaction between beta-arrestin2 and JNK3. JNK3-N-Tat exerted
      beneficial effects through pathways downstream of JNK3 and improved mitochondrial
      function, resulting in attenuated MPP+/MPTP-induced damage. JNK3-N-Tat protected
      mesencephalic dopaminergic neurons against MPTP-induced toxicity. CONCLUSIONS:
      JNK3-N-Tat, a JNK3-inhibitory peptide, protects dopaminergic neurons against
      MPP+/MPTP-induced injury by inhibiting the ASK1-JNK3 signaling pathway.

PMID- 25856435
TI  - Impact of weaning from acute dialytic therapy on outcomes of chronic kidney
      disease following urgent-start dialysis.
AB  - Discontinuation of acute, unplanned dialysis is always an important therapeutic
      goal in dialysis-requiring patients with existing chronic kidney disease. Only a
      limited proportion of patients could be weaned off dialysis and remained dialysis
      free. Here we performed a multicenter, observational study to investigate factors
      associated with successful weaning from acute dialysis, and to explore the
      potential impact of weaning itself on outcomes of patients with chronic kidney
      disease following urgent-start dialysis. We recruited 440 chronic kidney disease
      patients with a baseline estimated glomerular filtration rate <45 ml/min per 1/73
      m2, and used propensity score-adjusted Cox regression analysis to measure the
      effect of weaning from acute dialysis on death during the index hospitalization
      and death or readmission after discharge. Over 2 years, 64 of 421 (15.2%)
      patients who survived >1 month died, and 36 (8.6%) were removed from dialysis,
      with 26 (6.2%) remaining alive and dialysis-free. Logistic regression analysis
      found that age ? 65 years, ischemic acute tubular necrosis, nephrotoxic exposure,
      urinary obstruction, and higher predialysis estimated glomerular filtration rate
      and serum hemoglobin were predictors of weaning off dialysis. After adjustment
      for propensity scores for dialysis weaning, Cox proportional hazards models
      showed successful weaning from dialysis (adjusted hazard ratio 0.06; 95%
      confidence interval 0.01 to 0.35), along with a history of hypertension and serum
      albumin, were independent protectors for early death. Conversely, a history of
      stroke, peripheral arterial disease and cancer predicted the occurrence of early
      mortality. In conclusion, this prospective cohort study shows that compared to
      patients with chronic kidney disease who became end-stage renal disease after
      acute dialysis, patients who could be weaned off acute dialytic therapy were
      associated with reduced risk of premature death over a 2-year observation period.

PMID- 25856438
TI  - Unique macrocycles in the Taiwan traditional Chinese medicine database.
AB  - Chemical space coverage within natural product databases is an important
      criterion for the selection of databases for virtual screening. Chemical space
      analysis can also provide valuable hints towards chemical substructures that are
      responsible for medical activity. We therefore developed a protocol for
      structurally characterizing the chemical space covered in specific natural
      product databases by comparing it to a "standard" natural product scaffold
      distribution. In this contribution, we analyzed the structural characteristics of
      the traditional Chinese medicine database@Taiwan as an example. While we did not
      find classes of very characteristic small molecule scaffolds, we found that there
      are a number of specific macrocyclic scaffolds that are highly enriched in the
      traditional Chinese medicine database@Taiwan and not documented elsewhere. This
      surprising finding points towards underused regions in chemical space with a big
      potential for biological impact. 

PMID- 25856439
TI  - Production of Obionin A and Derivatives by the Sooty Blotch Fungus
      Microcyclospora malicola.
AB  - A multitude of sooty blotch and flyspeck fungi, mainly belonging to the
      Ascomycetes order Capnodiales, causes dark blemishes and flyspeck-like spots on
      apples worldwide. Different sooty blotch and flyspeck fungi can coexist in the
      same orchard and even on a single fruit. Our preceding experiments revealed an
      activity of Microcyclospora malicola strain 1930 against the anthracnose fungus
      Colletotrichum fioriniae in dual culture assays. Extracts of M. malicola strain
      1930 showed a broad bioactivity against filamentous fungus Mucor hiemalis and
      gram-positive bacterium Bacillus subtilis. A bioactivity-guided isolation led to
      the identification of obionin A (1) as the main active principle. In addition to
      1, which was previously isolated from the marine fungus Leptosphaeria obiones, we
      isolated three derivatives. Metabolite 2 bears a keto function at C-6, besides
      the replacement of oxygen by nitrogen at position 10. Two more derivatives are
      adducts (3, 4) of acetone as work-up artifacts. Because obionin A (1) and its
      derivative 2 showed cytotoxic effects and antifungal activities, we propose a
      role of these secondary metabolites in the antagonism between M. malicola and
      other apple colonizing sooty blotch and flyspeck fungi, other epiphytes, or apple
      pathogens competing for the same ecological niche. 

PMID- 25856440
TI  - Bisbenzylisoquinoline alkaloids from the roots of cyclea tonkinensis.
AB  - Cissampentine A (1), an enantiomer of cissampentin, three new cycleatjehenine
      type bisbenzylisoquinoline alkaloids, cissampentine B-D (2-4), and five known
      alkaloids were isolated from the roots of Cyclea tonkinensis. Their structures
      were established by interpretation of NMR, high-resolution ESI-MS data, and CD
      spectra. In vitro studies indicated that compounds 1 and 4 exhibited cytotoxicity
      against the HCT-8 tumor cell line (IC50 values of 8.97 and 9.73 uM,
      respectively), and compound 4 was also active against the Bel-7402 tumor cell
      line (IC50 value of 5.36 uM). 

PMID- 25856441
TI  - A Sensitive and Specific Indirect Competitive Enzyme-Linked Immunosorbent Assay
      for Detection of Paeoniflorin and Its Application in Pharmacokinetic Interactions
      between Paeoniflorin and Glycyrrhizinic Acid.
AB  - This study aimed to develop an indirect competitive enzyme-linked immunosorbent
      assay based on monoclonal antibodies against paeoniflorin to study the effects of
      different doses of glycyrrhizinic acid on the pharmacokinetics of paeoniflorin in
      mice. An anti-paeoniflorin monoclonal antibody was produced from a hybridoma
      created through a fusion of splenocytes immunized with paeoniflorin-bovine serum
      albumin and conjugated with the hypoxanthine-aminopterin-thymidine-sensitive
      mouse myeloma cell line SP2/0. The resultant antibody was used to develop and
      validate a rapid, specific and sensitive, indirect competitive enzyme-linked
      immunosorbent assay for the measurement of paeoniflorin (linear range 4.8-312.5
      ng . mL(-1)). The intraday and interday precision values of the indirect
      competitive ELISA method were well within the recommended range (<= 10 %), and
      the recovery rate was, on average, 101.13 %. Pharmacokinetic parameters obtained
      from mouse blood samples at various intervals following the oral administration
      of paeoniflorin and glycyrrhizic acid at three doses (1 : 0.3, 1 : 1, 1 : 3,
      respectively) demonstrated that the highest dose of glycyrrhizic acid inhibits
      the absorption of paeoniflorin. 

PMID- 25856442
TI  - DNA-Based Authentication of Botanicals and Plant-Derived Dietary Supplements:
      Where Have We Been and Where Are We Going?
AB  - Herbal medicines and botanicals have long been used as sole or additional medical
      aids worldwide. Currently, billions of dollars are spent on botanicals and
      related products, but minimal regulation exists regarding their purity,
      integrity, and efficacy. Cases of adulteration and contamination have led to
      severe illness and even death in some cases. Identifying the plant material in
      botanicals and phytomedicines using organoleptic means or through microscopic
      observation of plant parts is not trivial, and plants are often misidentified.
      Recently, DNA-based methods have been applied to these products because DNA is
      not changed by growth conditions unlike the chemical constituents of many active
      pharmaceutical agents. In recent years, DNA barcoding methods, which are used to
      identify species diversity in the Tree of Life, have been also applied to
      botanicals and plant-derived dietary supplements. In this review, we recount the
      history of DNA-based methods for identification of botanicals and discuss some of
      the difficulties in defining a specific bar code or codes to use. In addition, we
      describe how next generation sequencing technologies have enabled new techniques
      that can be applied to identifying these products with greater authority and
      resolution. Lastly, we present case histories where dietary supplements,
      decoctions, and other products have been shown to contain materials other than
      the main ingredient stipulated on the label. We conclude that there is a
      fundamental need for greater quality control in this industry, which if not self
      imposed, that may result from legislation. 

PMID- 25856445
TI  - The future of nursing: a worldwide perspective.

PMID- 25856444
TI  - A Promising Future for Optical Coherence Tomography Angiography.

PMID- 25856446
TI  - Professional development--not just for our learners.
AB  - Professional development is important for nurse educators. This article describes
      the experiences of three professional development nurses as they engaged in their
      own learning over the past year.

PMID- 25856443
TI  - Multi-parametric MRI at 14T for muscular dystrophy mice treated with AAV vector
      mediated gene therapy.
AB  - The objective of this study was to investigate the efficacy of using quantitative
      magnetic resonance imaging (MRI) as a non-invasive tool for the monitoring of
      gene therapy for muscular dystrophy. The clinical investigations for this family
      of diseases often involve surgical biopsy which limits the amount of information
      that can be obtained due to the invasive nature of the procedure. Thus, other non
      invasive tools may provide more opportunities for disease assessment and
      treatment responses. In order to explore this, dystrophic mdx4cv mice were
      systemically treated with a recombinant adeno-associated viral (AAV) vector
      containing a codon-optimized micro-dystrophin gene. Multi-parametric MRI of T2,
      magnetization transfer, and diffusion effects alongside 3-D volume measurements
      were then utilized to monitor disease/treatment progression. Mice were imaged at
      10 weeks of age for pre-treatment, then again post-treatment at 8, 16, and 24
      week time points. The efficacy of treatment was assessed by physiological assays
      for improvements in function and quantification of expression. Tissues from the
      hindlimbs were collected for histological analysis after the final time point for
      comparison with MRI results. We found that introduction of the micro-dystrophin
      gene restored some aspects of normal muscle histology and pathology such as
      decreased necrosis and resistance to contraction-induced injury. T2 relaxation
      values showed percentage decreases across all muscle types measured (tibialis
      anterior, gastrocnemius, and soleus) when treated groups were compared to
      untreated groups. Additionally, the differences between groups were statistically
      significant for the tibialis anterior as well. The diffusion measurements showed
      a wider range of percentage changes and less statistical significance while the
      magnetization transfer effect measurements showed minimal change. MR images
      displayed hyper-intense regions of muscle that correlated with muscle pathology
      in histological sections. T2 relaxation, alongside diffusion and magnetization
      transfer effects provides useful data towards the goal of non-invasively
      monitoring the treatment of muscular dystrophy. 

PMID- 25856447
TI  - Stroke prevention in nonvalvular atrial fibrillation: update on target-specific
      oral anticoagulants.
AB  - Atrial fibrillation is the most common arrhythmia in adults, and the risk for
      stroke is increased five-fold. Efforts should be made to educate health care
      providers to understand the importance of using risk stratification tools. New
      oral anticoagulants are available for thromboembolic stroke prevention, and
      knowledge of their clinical indications and use is essential.

PMID- 25856448
TI  - Identifying volition-driven leaders.
AB  - Professional development educators have access to health care practitioners at
      the onset of and throughout their employment. The educator-learner relationship
      presents an opportunity for educators to distinguish highly motivated individuals
      from those with the attribute known as volition. Motivation and volition are
      differentiated in this article.

PMID- 25856449
TI  - Tips for the use of simulation to maintain competency in performing high-risk/low
      frequency procedures.
AB  - Simulations are a way for educators to provide a safe way to maintain competency
      for procedural skills. Simulations allow for controlled evaluation and
      educational environments for both learners and educators. Helping the learner
      discern important information is a benefit of preforming high-risk/low-frequency
      skills during a simulation. High-risk/low-frequency simulations are a way to
      ensure that learners can perform procedures with infrequent clinical opportunity.

PMID- 25856450
TI  - Effects of perceived educational support on usage of an internet nursing
      reference center.
AB  - BACKGROUND: The need for evidence-based practice in nursing is well established;
      however, the efficacy of providing online research resources to nurses delivering
      care at the bedside has yet to undergo empirical testing. This study evaluated
      the impact of minimal educational support by a nurse researcher on nurses' usage
      of a hospital-based online nursing reference center. METHOD: This randomized,
      comparison group design feasibility study was conducted at a suburban medical
      center. Real-time RN usage of an online nursing reference center was collected
      over 10 months (August to May), with the comparative intervention occurring for
      seven of the 10 months (September to March). RESULTS: Independent samples t tests
      and analysis of variance demonstrated that nurses receiving weekly or biweekly
      visits from an educator had significantly higher usage of the reference center.
      CONCLUSIONS: Nurses who received minimal educational support through weekly and
      biweekly brief, verbally supportive visits from a nurse researcher were
      significantly higher users of the online nurse reference center than those
      receiving in-services only.

PMID- 25856452
TI  - A urinary incontinence continuing education online course for community health
      nurses in South Korea.
AB  - BACKGROUND: Although urinary incontinence is prevalent among older women living
      in rural Korea, a lack of awareness and education exists in this population and
      among health professionals. Geographic isolation and limited resources also
      contribute to having few educational offerings for rural nurses. The authors' aim
      was to develop an online continuing education course on continence care for
      community health nurses and to examine its effectiveness. METHOD: A one-group,
      pretest-posttest design was used to detect changes in knowledge and attitudes
      after taking the online education course. Participant satisfaction was also
      measured at the end of the training. RESULTS: A significant improvement in
      knowledge and attitudes toward continence care was noted. More than 95% of
      participants responded that they would recommend the online program to other
      health care providers and indicated the program would be helpful regarding
      continence care in their practice. CONCLUSION: The continuing education online
      course is a feasible strategy to support rural community health nurses' learning
      to improve knowledge and attitudes toward urinary incontinence management and
      care.

PMID- 25856453
TI  - Impact of a sepsis educational program on nurse competence.
AB  - Sepsis is an emerging life-threatening entity and a worldwide epidemic. Nurses
      are in key positions to identify patients with sepsis, mobilize the medical team,
      and implement interventions. A study of self-assessed nurse competence was
      conducted to determine the influence of a specially designed sepsis education
      program on nurses' perceived ability to identify early, intervene, and care for
      patients with sepsis. The program was a multimodal design incorporating online
      interactive didactic presentations, video vignettes, pre- and postknowledge
      tests, and high-fidelity medical simulation scenarios. A sample of 82 critical
      care and emergency department nurses in a 1-year critical care nurse training
      program was used for this study. Pretest and posttest module knowledge scores and
      self-assessed competence data were collected and analyzed. No improvement in the
      overall self-assessed competence scores was found; however, self-perceived
      frequency of use of competence behaviors improved. Participants felt more
      competent on three sepsis-targeted statements, and posttest knowledge scores
      showed significant improvement.

PMID- 25856454
TI  - Transitioning experienced registered nurses into an obstetrics specialty.
AB  - Ensuring patient safety and enhancing nurse satisfaction both rank high on most
      hospitals' list of priorities. One of the concerns at a large, comprehensive,
      county health care system in the southwestern United States has been the shortage
      of experienced obstetrics (OB) nurses to provide patient care. To address this
      concern, a nursing fellowship was implemented to facilitate successful transition
      and retention of experienced RNs into the specialty area of obstetrics. The
      program provided a gateway for non-OB nurses to participate in relevant, evidence
      based didactic and preceptor-facilitated clinical experiences to ensure adequate
      knowledge, skills, and competencies to care for patients in labor, delivery, and
      recovery suites.

PMID- 25856455
TI  - Highlights in metastatic breast cancer from the 2013 San Antonio Breast Cancer
      Symposium (SABCS).

PMID- 25856456
TI  - Highlights in metastatic breast cancer from the 2013 San Antonio Breast Cancer
      Symposium (SABCS): commentary.

PMID- 25856458
TI  - Highlights in lymphoma from the 12th International Conference on Malignant
      Lymphoma.

PMID- 25856457
TI  - Structure of the epiphyte community in a tropical montane forest in SW China.
AB  - Vascular epiphytes are an understudied and particularly important component of
      tropical forest ecosystems. However, owing to the difficulties of access, little
      is known about the properties of epiphyte-host tree communities and the factors
      structuring them, especially in Asia. We investigated factors structuring the
      vascular epiphyte-host community and its network properties in a tropical montane
      forest in Xishuangbanna, SW China. Vascular epiphytes were surveyed in six plots
      located in mature forests. Six host and four micro-site environmental factors
      were investigated. Epiphyte diversity was strongly correlated with host size
      (DBH, diameter at breast height), while within hosts the highest epiphyte
      diversity was in the middle canopy and epiphyte diversity was significantly
      higher in sites with canopy soil or a moss mat than on bare bark. DBH, elevation
      and stem height explained 22% of the total variation in the epiphyte species
      assemblage among hosts, and DBH was the most important factor which alone
      explained 6% of the variation. Within hosts, 51% of the variation in epiphyte
      assemblage composition was explained by canopy position and substrate, and the
      most important single factor was substrate which accounted for 16% of the
      variation. Analysis of network properties indicated that the epiphyte host
      community was highly nested, with a low level of epiphyte specialization, and an
      almost even interaction strength between epiphytes and host trees. Together,
      these results indicate that large trees harbor a substantial proportion of the
      epiphyte community in this forest. 

PMID- 25856459
TI  - Highlights in lymphoma from the 12th International Conference on Malignant
      Lymphoma: commentary.

PMID- 25856460
TI  - Including physicians in bundled hospital care payments: time to revisit an old
      idea?

PMID- 25856461
TI  - Association between phosphorus intake and bone health in the NHANES population.
AB  - The objective of this study was to estimate the independent associations between
      intake of phosphorus (P) and bone health parameters such as bone mineral content
      (BMC) and bone mineral density (BMD). It provides odds ratio (OR) of osteoporosis
      with quartiles of P intake adjusted for covariates (i.e., age, gender, BMI, and
      consumption of calcium (Ca), protein, total dairy foods, and vitamin D as well as
      intakes of supplemental Ca, vitamin D, and multivitamins/minerals). Data came
      from males and females aged 13-99 years who participated in the 2005-2010
      National Health and Nutrition Examination Survey (NHANES). Analyses showed that
      higher P intake was associated with higher Ca intake, and that dietary Ca:P
      ratios (0.51-0.62, with a mean of 0.60 for adults) were adequate in all
      age/gender groups. High intake of P was positively associated with BMC in female
      teenagers (Q4 vs. Q1: BMC, 30.9 +/- 1.1 vs. 29.0 +/- 0.5 g, P = 0.001). It was
      also positively associated with BMC and BMD as well as reduced risk of
      osteoporosis in adults >20 years of age (Q4 vs. Q1: OR of osteoporosis, 0.55; 95%
      confidence interval [CI], 0.39- 0.79; P = 0.001; BMC, 37.5 +/- 0.4 vs. 36.70 +/-
      0.3 g, P < 0.01; BMD, 0.986 +/- 0.004 vs. 0.966 +/- 0.005 g/cm(2), P < 0.05). The
      data suggest that high intake of P has no adverse effect on bone metabolism in
      populations with adequate Ca intake, and that it is also associated with positive
      bone parameters in some age/gender groups. 

PMID- 25856462
TI  - Strategies for tobacco control in India: a systematic review.
AB  - BACKGROUND: Tobacco control needs in India are large and complex. Evaluation of
      outcomes to date has been limited. AIM: To review the extent of tobacco control
      measures, and the outcomes of associated trialled interventions, in India.
      METHODS: Information was identified via database searches, journal hand-searches,
      reference and citation searching, and contact with experts. Studies of any
      population resident in India were included. Studies where outcomes were not yet
      available, not directly related to tobacco use, or not specific to India, were
      excluded. Pre-tested proformas were used for data extraction and quality
      assessment. Studies with reliability concerns were excluded from some aspects of
      analysis. The Framework Convention on Tobacco Control (FCTC) was use as a
      framework for synthesis. Heterogeneity limited meta-analysis options. Synthesis
      was therefore predominantly narrative. RESULTS: Additional to the Global Tobacco
      Surveillance System data, 80 studies were identified, 45 without reliability
      concerns. Most related to education (FCTC Article 12) and tobacco-use cessation
      (Article 14). They indicated widespread understanding of tobacco-related harm,
      but less knowledge about specific consequences of use. Healthcare professionals
      reported low confidence in cessation assistance, in keeping with low levels of
      training. Training for schoolteachers also appeared suboptimal. Educational and
      cessation assistance interventions demonstrated positive impact on tobacco use.
      Studies relating to smoke-free policies (Article 8), tobacco advertisements and
      availability (Articles 13 and 16) indicated increasingly widespread smoke-free
      policies, but persistence of high levels of SHS exposure, tobacco promotions and
      availability-including to minors. Data relating to taxation/pricing and packaging
      (Articles 6 and 11) were limited. We did not identify any studies of product
      regulation, alternative employment strategies, or illicit trade (Articles 9, 10,
      15 and 17). CONCLUSIONS: Tobacco-use outcomes could be improved by
      school/community-based and adult education interventions, and cessation
      assistance, facilitated by training for health professionals and schoolteachers.
      Additional tobacco control measures should be assessed.

PMID- 25856464
TI  - Proposed classification of auriculotemporal nerve, based on the root system.
AB  - The topography of the auriculotemporal nerve (ATN) root system is the main
      criterion of this nerve classification. Previous publications indicate that ATN
      may have between one and five roots. Most common is a one- or two-root variant of
      the nerve structure. The problem of many publications is the inconsistency of
      nomenclature which concerns the terms "roots", "connecting branches", or
      "branches" that are used to identify the same structures. This study was
      performed on 80 specimens (40 adults and 40 fetuses) to propose a classification
      based on: (i) the number of roots, (ii) way of root division, and (iii)
      configuration of interradicular fibers that form the ATN trunk. This new
      classification is a remedy for inconsistency of nomenclature of ATN in the
      infratemporal fossa. This classification system has proven beneficial when
      organizing all ATN variants described in previous studies and could become a
      helpful tool for surgeons and dentists. Examination of ATN from the infratemporal
      fossa of fetuses (the youngest was at 18 weeks gestational age) showed that, at
      that stage, the nerve is fully developed. 

PMID- 25856465
TI  - Highly enantioselective synthesis of naphthoquinones and pyranonaphthoquinones
      catalyzed by bifunctional chiral bis-squaramides.
AB  - A variety of enantioenriched naphthoquinones have been synthesized in high yields
      and excellent enantioselectivities (up to >99% ee) using a bifunctional chiral
      bis-squaramide catalyzed conjugate addition of 2-hydroxy-1,4-naphthoquinone to 2
      enoylpyridines. Some of the Michael products have been successfully converted
      into various enantioenriched pyranonaphthoquinone derivatives. The protocol is
      further extended to the synthesis of various 4-hydroxycoumarin derivatives under
      mild conditions. 

PMID- 25856467
TI  - Cell shape-dependent shear stress on adherent cells in a micro-physiologic system
      as revealed by FEM.
AB  - Flow-induced shear stress on adherent cells leads to biochemical signaling and
      mechanical responses of the cells. To determine the flow-induced shear stress on
      adherent cells cultured in a micro-scaled reaction chamber, we developed a
      suitable finite element method model. The influence of the most important
      parameters-cell shape, cell density, shear modulus and fluid velocity-was
      investigated. Notably, the cell shape strongly influences the resulting shear
      stress. Long and smooth cells undergo lower shear stress than more rounded cells.
      Changes in the curvature of the cells lead to stress peaks and single cells
      experience higher shear stress values than cells of a confluent monolayer. The
      computational results of the fluid flow simulation were validated experimentally.
      We also analyzed the influence of flow-induced shear stress on the metabolic
      activity and shape of L929, a mouse fibroblast cell line, experimentally. The
      results indicate that threshold stress values for continuous flow conditions
      cannot be transferred to quasi static flow conditions interrupted by short fluid
      exchange events. 

PMID- 25856466
TI  - Let-7, mir-98 and mir-183 as biomarkers for cancer and schizophrenia [corrected].
AB  - Recent evidence supports a role of microRNAs in cancer and psychiatric disorders
      such as schizophrenia and bipolar disorder, through their regulatory role on the
      expression of multiple genes. The rather rare co-morbidity of cancer and
      schizophrenia is an old hypothesis which needs further research on microRNAs as
      molecules that might exert their oncosuppressive or oncogenic activity in the
      context of their role in psychiatric disorders. The expression pattern of a
      variety of different microRNAs was investigated in patients (N = 6) suffering
      from schizophrenia termed control, patients with a solid tumor (N = 10) and
      patients with both schizophrenia and tumor (N = 8). miRNA profiling was performed
      on whole blood samples using the miRCURY LNA microRNA Array technology (6th & 7th
      generation). A subset of 3 microRNAs showed a statistically significant
      differential expression between the control and the study groups. Specifically,
      significant down-regulation of the let-7p-5p, miR-98-5p and of miR-183-5p in the
      study groups (tumor alone and tumorand schizophrenia) was observed (p<0.05). The
      results of the present study showed that let-7, miR-98 and miR-183 may play an
      important oncosuppressive role through their regulatory impact in gene expression
      irrespective of the presence of schizophrenia, although a larger sample size is
      required to validate these results. Nevertheless, further studies are warranted
      in order to highlight a possible role of these and other micro-RNAs in the
      molecular pathways of schizophrenia. 

PMID- 25856468
TI  - Associations between Difficulty Paying Medical Bills and Forgone Medical and
      Prescription Drug Care.
AB  - Problems paying medical bills have been reported to be associated with increased
      stress, bankruptcy, and forgone medical care. Using the Behavioral Model for
      Vulnerable Populations developed by Gelberg et al as a framework, as well as data
      from the 2010 Ohio Family Health Survey, this study examined the relationships
      between difficulty paying medical bills and forgone medical and prescription drug
      care. Logistic regression was used to examine associations between difficulty
      paying medical bills and predisposing, enabling, need (health status), and health
      behaviors (forgoing medical care). Difficulty paying medical bills increased the
      effect of lack of health insurance in predicting forgone medical care and had a
      conditional effect on the association between education and forgone prescription
      drug care. Those who had less than a bachelor's degree were more likely to forgo
      prescription drug care than those with a bachelor's degree, but only if they had
      difficulty paying medical bills. Difficulty paying medical bills also accounted
      for the relationships between several population characteristics (eg, age,
      income, home ownership, health status) in predicting forgone medical and
      prescription drug care. Policies to cap out-of-pocket medical expenses may
      mitigate health disparities by addressing the impact of difficulty paying medical
      bills on forgone care.

PMID- 25856469
TI  - Effects of Hydration and Calcium Supplementation on Urine Calcium Concentration
      in Healthy Postmenopausal Women.
AB  - OBJECTIVE: The aim of this study was to determine whether calcium
      supplementation, compared with placebo, increases urine calcium concentrations to
      levels indicative of increased renal stone risk, and the role that fluid intake,
      as indicated by urine volume, may play in mitigating this risk. METHODS: This is
      a secondary analysis of data from a randomized placebo-controlled trial of 500
      mg/d calcium supplementation to prevent bone loss. Subjects were 240 white
      postmenopausal women age 40 to 70 years in good general health. Effects of
      supplementation on 1-year changes in 24h urine calcium concentration and urine
      volume were examined. RESULTS: Both treatment group and urine volume were strong
      independent predictors of urine calcium concentration (p < 0.001). Among subjects
      with urine volume under 2 L/24 h, more than half of placebo subjects were at
      lowest risk for renal stones compared with less than 35% of calcium-supplemented
      subjects. Among those with higher urine volumes, all placebo subjects and more
      than 80% of calcium supplemented subjects were at lowest risk. CONCLUSIONS: The
      increased risk of renal stones with calcium supplement use may be largely
      eliminated with adequate fluid intake, but older adults may not spontaneously
      consume adequate fluids to minimize this risk and should be counseled to do so.

PMID- 25856470
TI  - Catalytic reaction processes revealed by scanning probe microscopy. [corrected].
AB  - Heterogeneous catalysis is of great importance for modern society. About 80% of
      the chemicals are produced by catalytic reactions. Green energy production and
      utilization as well as environmental protection also need efficient catalysts.
      Understanding the reaction mechanisms is crucial to improve the existing
      catalysts and develop new ones with better activity, selectivity, and stability.
      Three components are involved in one catalytic reaction: reactant, product, and
      catalyst. The catalytic reaction process consists of a series of elementary
      steps: adsorption, diffusion, reaction, and desorption. During reaction, the
      catalyst surface can change at the atomic level, with roughening, sintering, and
      segregation processes occurring dynamically in response to the reaction
      conditions. Therefore, it is imperative to obtain atomic-scale information for
      understanding catalytic reactions. Scanning probe microscopy (SPM) is a very
      appropriate tool for catalytic research at the atomic scale because of its unique
      atomic-resolution capability. A distinguishing feature of SPM, compared to other
      surface characterization techniques, such as X-ray photoelectron spectroscopy, is
      that there is no intrinsic limitation for SPM to work under realistic reaction
      conditions (usually high temperature and high pressure). Therefore, since it was
      introduced in 1981, scanning tunneling microscopy (STM) has been widely used to
      investigate the adsorption, diffusion, reaction, and desorption processes on
      solid catalyst surfaces at the atomic level. STM can also monitor dynamic changes
      of catalyst surfaces during reactions. These invaluable microscopic insights have
      not only deepened the understanding of catalytic processes, but also provided
      important guidance for the development of new catalysts. This Account will focus
      on elementary reaction processes revealed by SPM. First, we will demonstrate the
      power of SPM to investigate the adsorption and diffusion process of reactants on
      catalyst surfaces at the atomic level. Then the dynamic processes, including
      surface reconstruction, roughening, sintering, and phase separation, studied by
      SPM will be discussed. Furthermore, SPM provides valuable insights toward
      identifying the active sites and understanding the reaction mechanisms. We also
      illustrate here how both ultrahigh vacuum STM and high pressure STM provide
      valuable information, expanding the understanding provided by traditional surface
      science. We conclude with highlighting remarkable recent progress in noncontact
      atomic force microscopy (NC-AFM) and inelastic electron tunneling spectroscopy
      (IETS), and their impact on single-chemical-bond level characterization for
      catalytic reaction processes in the future. 

PMID- 25856471
TI  - Research Forum on Challenges in Hearing Health Care for the Oldest Older Adults.
AB  - PURPOSE: The purpose of this article is to introduce the invited Research Forum
      on challenges in hearing health care for the oldest older adults, which was
      presented at the 2014 HEaring Across the Lifespan conference (HEAL 2014). METHOD:
      A brief overview of the three presentations in the special session is provided
      along with general conclusions. CONCLUSIONS: Hearing health care needs of the
      oldest older adults are multifactorial and are related to auditory and cognitive
      declines; social, emotional, and lifestyle changes; and increasing physical
      disabilities and other comorbidities. Improved clinical outcomes for hearing
      health require personalized needs assessments by interprofessional teams and
      shared decision making on treatment options.

PMID- 25856472
TI  - Serial Measurement of Amino-Terminal Pro-B-Type Natriuretic Peptide Predicts
      Adverse Cardiovascular Outcome in Children With Primary Myocardial Dysfunction
      and Acute Decompensated Heart Failure.
AB  - OBJECTIVES: In children, elevated amino-terminal pro-B-type natriuretic peptide
      levels are associated with impaired heart function. The predictive value of
      serial monitoring of amino-terminal pro-B-type natriuretic peptide levels in
      acute decompensated heart failure is unclear. DESIGN: Prospective observational
      study. SETTING: Single, tertiary referral pediatric critical care unit. PATIENTS:
      Patients aged 0-21 years with primary myocardial dysfunction and acute
      decompensated heart failure. INTERVENTIONS: Amino-terminal pro-B-type natriuretic
      peptide levels were obtained on enrollment, day 2, and day 7. Clinical,
      laboratory, and imaging data were collected on enrollment. Adverse cardiovascular
      outcome was defined as heart transplant, ventricular assist device placement,
      extracorporeal membrane oxygenation, or death at 1 year after admission.
      Aminoterminal pro-B-type natriuretic peptide levels and the percent change from
      day 0 to day 2 and day 0 to day 7 were calculated and compared between those with
      and without adverse cardiovascular outcome. MEASUREMENTS AND MAIN RESULTS:
      Sixteen consecutive patients were enrolled. Adverse cardiovascular outcome
      occurred in six patients (37.5%, four heart transplant and two ventricular assist
      device). In patients with an adverse cardiovascular outcome, median amino
      terminal pro-B-type natriuretic peptide levels at day 7 were significantly higher
      (7,365 vs 1,196 pg/mL; p = 0.02) and the percent decline in amino-terminal pro-B
      type natriuretic peptide was significantly smaller (28% vs 73%; p = 0.02)
      compared with those without an adverse cardiovascular outcome. Receiver operating
      curve analysis revealed that a less than 55% decline in amino-terminal pro-B-type
      natriuretic peptide levels at day 7 had a sensitivity and specificity of 83% and
      90%, respectively, in predicting an adverse cardiovascular (area under the curve,
      0.86; 95% CI, 0.68-1.0; p = 0.02). CONCLUSIONS: In conclusion, children with
      primary myocardial dysfunction and acute decompensated heart failure, a
      persistently elevated amino-terminal pro-B-type natriuretic peptide, and/or a
      lesser degree of decline in amino-terminal pro-B-type natriuretic peptide during
      the first week of presentation were strongly associated with adverse
      cardiovascular outcome. Serial amino-terminal pro-B-type natriuretic peptide
      monitoring may allow the early identification of children at risk for worse
      outcome.

PMID- 25856473
TI  - Acute Kidney Injury in Pediatric Acute Decompensated Heart Failure.
AB  - OBJECTIVE: Acute kidney injury in adult patients with acute decompensated heart
      failure is associated with increased mortality. There is limited literature in
      pediatric patients with acute decompensated heart failure and acute kidney
      injury. We aim to study acute kidney injury in the pediatric acute decompensated
      heart failure population and its association with specific outcomes. DESIGN:
      Retrospective, case-control study. SETTING: Cardiac ICU in a children's tertiary
      care hospital. PATIENTS: Index admissions of patients younger than 21 years with
      acute decompensated heart failure between January 2008 and December 2012.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Index admissions of patients
      younger than 21 years with acute decompensated heart failure between January 2008
      and December 2012 were reviewed, and the presence or absence of acute kidney
      injury at admission was determined based on the Pediatric Risk, Injury, Failure,
      Loss, End-Stage criteria. Descriptive statistics and multivariate analyses were
      performed to determine the association between acute kidney injury and a
      composite outcome of cardiac transplantation and/or mortality. Fifty-seven
      patients, with median age 12 years (interquartile range, 1.1, 16), were included
      for study. The median left ventricular ejection fraction was 27% (interquartile
      range, 18, 48). Twenty-one patients (36%) underwent cardiac transplantation and
      five patients (8.7%) died. Of the 57 patients, 44 (77%) had evidence of acute
      kidney injury (41% Risk; 39% Injury; 20% Failure). Of the 44 patients with acute
      kidney injury, 25 (57%) met the composite outcome, compared with 1 (7%) without
      acute kidney injury. Multivariate analyses demonstrated that a left ventricular
      ejection fraction up to 25% was significantly associated with the presence of
      acute kidney injury (adjusted odds ratio, 12.3; 95% CI, 1.4-109; p = 0.03), and
      acute kidney injury was significantly associated with the composite outcome
      (adjusted odds ratio, 19.1; 95% CI, 2.3-160; p < 0.001). CONCLUSIONS: Acute
      kidney injury is common during the initial presentation of pediatric patients
      with acute decompensated heart failure. A left ventricular ejection fraction up
      to 25% is associated with acute kidney injury. The presence of acute kidney
      injury in this population is significantly associated with cardiac
      transplantation and/or death.

PMID- 25856474
TI  - Exploring neurotechnologies.

PMID- 25856475
TI  - Macrophage migration inhibitory factor, the Zelig of cytokines, is a chaperone
      for SOD1 in non-neuronal cells.
AB  - Pathogenic properties of mutant SOD1 in ALS likely involve binding to
      mitochondrial and ER membranes. In this issue of Neuron, Israelson et al. (2015)
      show that motor neurons, selectively vulnerable in ALS, lack a chaperone that
      precludes mSOD1 binding intracellular membranes in other cells. This chaperone is
      identified as the pleiotropic cytokine macrophage migration inhibitory factor.

PMID- 25856476
TI  - Enhanced dendritic integration by ih reduction in the anterior cingulate cortex
      increases nociception.
AB  - In this issue of Neuron, Santello and Nevian (2015) report HCN channel plasticity
      and increased temporal summation in layer 5 ACC neurons following nerve injury.
      They are able to restore HCN channel function and reduce behavioral
      hypersensitivity with selective serotonin receptor targeting. 

PMID- 25856477
TI  - Gene regulation: it matters who you hang out with.
AB  - How broadly expressed transcription factors contribute to tissue-specific gene
      expression is not well understood. Andzelm, Cherry et al. (2015) demonstrate that
      myocyte enhancer factor 2D (MEF2D) binds and activates retina-specific regulatory
      regions by cooperative interaction with the tissue-specific transcription factor
      CRX.

PMID- 25856478
TI  - Unraveling a locomotor network, many neurons at a time.
AB  - In this issue of Neuron, Bruno et al. (2015) use large-scale recordings in
      Aplysia, and apply novel dimensionality-reduction techniques to define dynamical
      building blocks involved in locomotor behavior. These techniques open new avenues
      to the study of neuronal networks.

PMID- 25856479
TI  - Seeking a roadmap toward neuroepigenetics.
AB  - A group of papers investigates functional regulatory elements in genomes from
      human tissue samples and cell lines. What can neuroscientists learn from the
      gigantic data set and how will it affect the direction of neuroepigenetics? 

PMID- 25856480
TI  - Engineering the next generation of brain scientists.
AB  - New technologies to probe the nervous system are propelling innovation and
      discovery at blinding speed, but are our trainees prepared to maximize this
      power? The growing role of engineering in research, such as materials, computing,
      electronics, and devices, compels us to rethink neuroscience education. Core
      technology requirements, cross-disciplinary education, open-source resources, and
      experiential learning are new ways we can efficiently equip future leaders to
      make the next disruptive discoveries.

PMID- 25856481
TI  - Beyond the patch clamp: nanotechnologies for intracellular recording.
AB  - The patch clamp is a fundamental tool for neuroscientists, offering insights that
      have shaped our understanding of the brain. Advances in nanotechnology suggest
      that the next generation of recording methods is now within reach. We discuss the
      complexity and future promise of applying nanoscience to neural recording. 

PMID- 25856482
TI  - The mutual inspirations of machine learning and neuroscience.
AB  - Neuroscientists are generating data sets of enormous size, which are matching the
      complexity of real-world classification tasks. Machine learning has helped data
      analysis enormously but is often not as accurate as human data analysis. Here,
      Helmstaedter discusses the challenges and promises of neuroscience-inspired
      machine learning that lie ahead. 

PMID- 25856483
TI  - Defining ecological strategies in neuroprosthetics.
AB  - Neurological disorders disrupt the equilibrium within the brain and spinal cord
      ecosystems. Ecology reuses, recycles, and reduces to help maintain the balance
      across ecosystems. Likewise, neuroprosthetics can help the brain help itself with
      ecoprosthetic designs that integrate the principles of the "three 'R's." 

PMID- 25856484
TI  - An ethics toolbox for neurotechnology.
AB  - Advances in neurotechnology will raise new ethical dilemmas, to which scientists
      and the rest of society must respond. Here I present a "toolbox" of concepts to
      help us analyze these issues and communicate with each other about them across
      differences of ethical intuition.

PMID- 25856486
TI  - Brain-machine interfaces beyond neuroprosthetics.
AB  - The field of invasive brain-machine interfaces (BMIs) is typically associated
      with neuroprosthetic applications aiming to recover loss of motor function.
      However, BMIs also represent a powerful tool to address fundamental questions in
      neuroscience. The observed subjects of BMI experiments can also be considered as
      indirect observers of their own neurophysiological activity, and the relationship
      between observed neurons and (artificial) behavior can be genuinely causal rather
      than indirectly correlative. These two characteristics defy the classical object
      observer duality, making BMIs particularly appealing for investigating how
      information is encoded and decoded by neural circuits in real time, how this
      coding changes with physiological learning and plasticity, and how it is altered
      in pathological conditions. Within neuroengineering, BMI is like a tree that
      opens its branches into many traditional engineering fields, but also extends
      deep roots into basic neuroscience beyond neuroprosthetics. 

PMID- 25856487
TI  - Towards large-scale, human-based, mesoscopic neurotechnologies.
AB  - Direct human brain recordings have transformed the scope of neuroscience in the
      past decade. Progress has relied upon currently available neurophysiological
      approaches in the context of patients undergoing neurosurgical procedures for
      medical treatment. While this setting has provided precious opportunities for
      scientific research, it also has presented significant constraints on the
      development of new neurotechnologies. A major challenge now is how to achieve
      high-resolution spatiotemporal neural recordings at a large scale. By narrowing
      the gap between current approaches, new directions tailored to the mesoscopic
      (intermediate) scale of resolution may overcome the barriers towards safe and
      reliable human-based neurotechnology development, with major implications for
      advancing both basic research and clinical translation. 

PMID- 25856485
TI  - Neuromechanical principles underlying movement modularity and their implications
      for rehabilitation.
AB  - Neuromechanical principles define the properties and problems that shape neural
      solutions for movement. Although the theoretical and experimental evidence is
      debated, we present arguments for consistent structures in motor patterns, i.e.,
      motor modules, that are neuromechanical solutions for movement particular to an
      individual and shaped by evolutionary, developmental, and learning processes. As
      a consequence, motor modules may be useful in assessing sensorimotor deficits
      specific to an individual and define targets for the rational development of
      novel rehabilitation therapies that enhance neural plasticity and sculpt motor
      recovery. We propose that motor module organization is disrupted and may be
      improved by therapy in spinal cord injury, stroke, and Parkinson's disease.
      Recent studies provide insights into the yet-unknown underlying neural mechanisms
      of motor modules, motor impairment, and motor learning and may lead to better
      understanding of the causal nature of modularity and its underlying neural
      substrates. 

PMID- 25856488
TI  - The emergence of single neurons in clinical neurology.
AB  - Single neuron actions and interactions are the sine qua non of brain function,
      and nearly all diseases and injuries of the CNS trace their clinical sequelae to
      neuronal dysfunction or failure. Remarkably, discussion of neuronal activity is
      largely absent in clinical neuroscience. Advances in neurotechnology and
      computational capabilities, accompanied by shifts in theoretical frameworks, have
      led to renewed interest in the information represented by single neurons. Using
      direct interfaces with the nervous system, millisecond-scale information will
      soon be extracted from single neurons in clinical environments, supporting
      personalized treatment of neurologic and psychiatric disease. In this
      Perspective, we focus on single-neuronal activity in restoring communication and
      motor control in patients suffering from devastating neurological injuries. We
      also explore the single neuron's role in epilepsy and movement disorders,
      surgical anesthesia, and in cognitive processes disrupted in neurodegenerative
      and neuropsychiatric disease. Finally, we speculate on how technological advances
      will revolutionize neurotherapeutics. 

PMID- 25856489
TI  - Tools for probing local circuits: high-density silicon probes combined with
      optogenetics.
AB  - To understand how function arises from the interactions between neurons, it is
      necessary to use methods that allow the monitoring of brain activity at the
      single-neuron, single-spike level and the targeted manipulation of the diverse
      neuron types selectively in a closed-loop manner. Large-scale recordings of
      neuronal spiking combined with optogenetic perturbation of identified individual
      neurons has emerged as a suitable method for such tasks in behaving animals. To
      fully exploit the potential power of these methods, multiple steps of technical
      innovation are needed. We highlight the current state of the art in
      electrophysiological recording methods, combined with optogenetics, and discuss
      directions for progress. In addition, we point to areas where rapid development
      is in progress and discuss topics where near-term improvements are possible and
      needed. 

PMID- 25856493
TI  - Soft materials in neuroengineering for hard problems in neuroscience.
AB  - We describe recent advances in soft electronic interface technologies for
      neuroscience research. Here, low modulus materials and/or compliant mechanical
      structures enable modes of soft, conformal integration and minimally invasive
      operation that would be difficult or impossible to achieve using conventional
      approaches. We begin by summarizing progress in electrodes and associated
      electronics for signal amplification and multiplexed readout. Examples in large
      area, surface conformal electrode arrays and flexible, multifunctional depth
      penetrating probes illustrate the power of these concepts. A concluding section
      highlights areas of opportunity in the further development and application of
      these technologies. 

PMID- 25856490
TI  - Closed-loop and activity-guided optogenetic control.
AB  - Advances in optical manipulation and observation of neural activity have set the
      stage for widespread implementation of closed-loop and activity-guided optical
      control of neural circuit dynamics. Closing the loop optogenetically (i.e.,
      basing optogenetic stimulation on simultaneously observed dynamics in a
      principled way) is a powerful strategy for causal investigation of neural
      circuitry. In particular, observing and feeding back the effects of circuit
      interventions on physiologically relevant timescales is valuable for directly
      testing whether inferred models of dynamics, connectivity, and causation are
      accurate in vivo. Here we highlight technical and theoretical foundations as well
      as recent advances and opportunities in this area, and we review in detail the
      known caveats and limitations of optogenetic experimentation in the context of
      addressing these challenges with closed-loop optogenetic control in behaving
      animals.

PMID- 25856491
TI  - Cellular level brain imaging in behaving mammals: an engineering approach.
AB  - Fluorescence imaging offers expanding capabilities for recording neural dynamics
      in behaving mammals, including the means to monitor hundreds of cells targeted by
      genetic type or connectivity, track cells over weeks, densely sample neurons
      within local microcircuits, study cells too inactive to isolate in extracellular
      electrical recordings, and visualize activity in dendrites, axons, or dendritic
      spines. We discuss recent progress and future directions for imaging in behaving
      mammals from a systems engineering perspective, which seeks holistic
      consideration of fluorescent indicators, optical instrumentation, and
      computational analyses. Today, genetically encoded indicators of neural Ca(2+)
      dynamics are widely used, and those of trans-membrane voltage are rapidly
      improving. Two complementary imaging paradigms involve conventional microscopes
      for studying head-restrained animals and head-mounted miniature microscopes for
      imaging in freely behaving animals. Overall, the field has attained sufficient
      sophistication that increased cooperation between those designing new indicators,
      light sources, microscopes, and computational analyses would greatly benefit
      future progress. 

PMID- 25856492
TI  - Cell-based screening: extracting meaning from complex data.
AB  - Unbiased discovery approaches have the potential to uncover neurobiological
      insights into CNS disease and lead to the development of therapies. Here, we
      review lessons learned from imaging-based screening approaches and recent
      advances in these areas, including powerful new computational tools to synthesize
      complex data into more useful knowledge that can reliably guide future research
      and development.

PMID- 25856496
TI  - Staining intraoperative topical solutions with fluorescein: enhancing the safety
      of sinus surgery.
AB  - BACKGROUND: Oxymetazoline HCl 0.05%, 1:100,000 lidocaine with epinephrine
      (lido+epi), and 1:1000 epinephrine are all colorless solutions employed in sinus
      surgery. Because lido+epi is injected whereas others are not, care must be taken
      to label all solutions to avoid inadvertent injection of oxymetazoline or
      concentrated epinephrine because of life-threatening complications. Dyes have
      been used to color solutions for visual identification, but efficacy and cost
      have never been compared. We sought to determine the effectiveness of surgical
      marking pen (gentian violet) and fluorescein strips as coloring agents in mediums
      commonly used in sinus surgery. METHODS: In this specialty techniques study, 4
      liquid mediums (normal saline [NS], 0.05% oxymetazoline, 1:1,000 epinephrine, and
      lido+epi) and 2 coloring agents (fluorescein strip and surgical marking pen) were
      combined separately. Photos and absorbance of each solution were obtained at 15
      minute intervals over 2 hours using a spectrophotometer. RESULTS: Peak absorbance
      remained stable for all solutions with fluorescein. Absorbance also remained
      constant for NS (0.37 absorbance units [AU] -> 0.37 AU) and oxymetazoline (2.8 AU
      -> 2.8 AU) mixed with marking pen. Absorbance decreased over 2 hours when marking
      pen was mixed with 1:1000 epinephrine (0.82 AU -> 0.32 AU) and lido+epi (1.19 AU 
      > 0.33 AU). Furthermore, the majority of color visibility and absorbance
      decreased in the first 15 minutes for concentrated epinephrine (0.82 -> 0.33) and
      lido+epi (1.19 -> 0.51). Cost of fluorescein strips ($0.14 to $0.20/strip) was
      less than marking pens ($13 to 46/pen). CONCLUSION: Compared to marking pen dye,
      solutions dyed with fluorescein retained their color and did not decay over time.
      We recommend fluorescein strips to label colorless materials in the operating
      room because of their lack of color decay and cost advantages.

PMID- 25856495
TI  - Morbidity and mortality according to latest CD4+ cell count among HIV positive
      individuals in South Africa who enrolled in project Phidisa.
AB  - BACKGROUND: Short-term morbidity and mortality rates for HIV positive soldiers in
      the South African National Defence Force (SANDF) would inform decisions about
      deployment and HIV disease management. Risks were determined according to the
      latest CD4+ cell count and use of antiretroviral therapy (ART) for HIV positive
      individuals in the SANDF and their dependents. METHODS AND FINDINGS: A total of
      7,114 participants were enrolled and followed for mortality over a median of 4.7
      years (IQR: 1.9, 7.1 years). For a planned subset (5,976), progression of disease
      (POD) and grade 4, potentially life-threatening events were also ascertained.
      CD4+ count and viral load were measured every 3 to 6 months. Poisson regression
      was used to compare event rates by latest CD4+ count (<50, 50-99, 100-199, 200
      349, 350-499, 500+) with a focus on upper three strata, and to estimate relative
      risks (RRs) (ART/no ART). Median entry CD4+ was 207 cells/mm3. During follow-up
      over 70% were prescribed ART. Over follow-up 1,226 participants died; rates
      ranged from 57.6 (< 50 cells) to 0.8 (500+ cells) per 100 person years (py).
      Compared to those with latest CD4+ 200-349 (2.2/100 py), death rates were
      significantly lower (p<0.001), as expected, for those with 350-499 (0.9/100 py)
      and with 500+ cells (0.8/100 py). The composite outcome of death, POD or grade 4
      events occurred in 2,302 participants (4,045 events); rates were similar in
      higher CD4+ count strata (9.4 for 350-499 and 7.9 for 500+ cells) and lower than
      those with counts 200-349 cells (13.5) (p<0.001). For those with latest CD4+ 350+
      cells, 63% of the composite outcomes (680 of 1,074) were grade 4 events.
      CONCLUSION: Rates of morbidity and mortality are lowest among those with CD4+
      count of 350 or higher and rates do not differ for those with counts of 350-499
      versus 500+ cells. Grade 4 events are the predominant morbidity for participants
      with CD4+ counts of 350+ cells.

PMID- 25856497
TI  - Oral Administration of Aloe vera (L.) Burm. f. (Xanthorrhoeaceae) and Honey
      Improves the Host Body Composition and Modulates Proteolysis Through Reduction of
      Tumor Progression and Oxidative Stress in Rats.
AB  - Oxidative stress has a dual role in cancer; it is linked with tumorigenic events
      and host wasting, as well as senescence and apoptosis. Researchers have
      demonstrated the importance of coadjuvant therapies in cancer treatment, and Aloe
      vera and honey have immunomodulatory, anticancer, and antioxidant properties. The
      preventive and therapeutic effects of Aloe vera (L.) Burm. f. (Xanthorrhoeaceae)
      and honey in tumor progression and host wasting were analyzed in Walker 256
      carcinoma-bearing rats. The animals were distributed into the following groups:
      C=control-untreated, W=tumor-untreated, WA=treated after tumor induction,
      A=control-treated, AW=treated before tumor induction, and AWA=treated before and
      after tumor induction. Proteolysis and oxidative stress were analyzed in the
      tumor, liver, muscle, and myocardial tissues. The results suggest that the Aloe
      vera and honey treatment affect the tumor and host by different mechanisms; the
      treatment-modulated host wasting and cachexia, whereas it promoted oxidative
      stress and damage in tumor tissues, particularly in a therapeutic context (WA). 

PMID- 25856498
TI  - Rapid and portable electrochemical quantification of phosphorus.
AB  - Phosphorus is one of the key indicators of eutrophication levels in natural
      waters where it exists mainly as dissolved phosphorus. Various analytical
      protocols exist to provide an offsite analysis, and a point of site analysis is
      required. The current standard method recommended by the Environmental Protection
      Agency (EPA) for the detection of total phosphorus is colorimetric and based upon
      the color of a phosphomolybdate complex formed as a result of the reaction
      between orthophosphates and molybdates ions where ascorbic acid and antimony
      potassium tartrate are added and serve as reducing agents. Prior to the
      measurements, all forms of phosphorus are converted into orthophosphates via
      sample digestion (heating and acidifying). The work presented here details an
      electrochemical adaptation of this EPA recommended colorimetric approach for the
      measurement of dissolved phosphorus in water samples using screen-printed
      graphite macroelectrodes for the first time. This novel indirect electrochemical
      sensing protocol allows the determination of orthophosphates over the range from
      0.5 to 20 MUg L(-1) in ideal pH 1 solutions utilizing cyclic voltammetry with a
      limit of detection (3sigma) found to correspond to 0.3 MUg L(-1) of phosphorus.
      The reaction time and influence of foreign ions (potential interferents) upon
      this electroanalytical protocol was also investigated, where it was found that a
      reaction time of 5 min, which is essential in the standard colorimetric approach,
      is not required in the new proposed electrochemically adapted protocol. The
      proposed electrochemical method was independently validated through the
      quantification of orthophosphates and total dissolved phosphorus in polluted
      water samples (canal water samples) with ion chromatography and ICP-OES,
      respectively. This novel electrochemical protocol exhibits advantages over the
      established EPA recommended colorimetric determination for total phosphorus with
      lower detection limits and shorter experimental times. Additionally this
      electrochemical adaptation allows the determination of dissolved phosphorus
      without the use of ascorbic acid and antimony potassium tartrate as reducing
      agents (as used in the colorimetric method). The potential portability of this
      protocol is demonstrated in the development of the PhosQuant electrochemical
      device and provides a portable device for the rapid electrochemical detection of
      dissolved phosphorus using screen-printed electrodes. 

PMID- 25856499
TI  - Codoping in SnTe: Enhancement of Thermoelectric Performance through Synergy of
      Resonance Levels and Band Convergence.
AB  - We report a significant enhancement of the thermoelectric performance of p-type
      SnTe over a broad temperature plateau with a peak ZT value of ~1.4 at 923 K
      through In/Cd codoping and a CdS nanostructuring approach. Indium and cadmium
      play different but complementary roles in modifying the valence band structure of
      SnTe. Specifically, In-doping introduces resonant levels inside the valence
      bands, leading to a considerably improved Seebeck coefficient at low temperature.
      Cd-doping, however, increases the Seebeck coefficient of SnTe remarkably in the
      mid- to high-temperature region via a convergence of the light and heavy hole
      bands and an enlargement of the band gap. Combining the two dopants in SnTe
      yields enhanced Seebeck coefficient and power factor over a wide temperature
      range due to the synergy of resonance levels and valence band convergence, as
      demonstrated by the Pisarenko plot and supported by first-principles band
      structure calculations. Moreover, these codoped samples can be hierarchically
      structured on all scales (atomic point defects by doping, nanoscale
      precipitations by CdS nanostructuring, and mesoscale grains by SPS treatment) to
      achieve highly effective phonon scattering leading to strongly reduced thermal
      conductivities. In addition to the high maximum ZT the resultant large average ZT
      of ~0.8 between 300 and 923 K makes SnTe an attractive p-type material for high
      temperature thermoelectric power generation. 

PMID- 25856500
TI  - Cosmetic effect of knee joint in a knee disarticulation prosthesis.
AB  - Despite numerous advantages, knee disarticulations (KDs) are rarely performed
      because of the anticipated KD prosthesis fitting problems that include the
      positioning of the knee joint distally from the KD socket. This results in
      lengthening of the thigh and subsequent shortening of the shank. The objective of
      this study was to assess the cosmetic effect of the knee joint in a KD prosthesis
      by determining the extent of the lengthening of the thigh and the shortening of
      the shank. This lengthening and shortening were measured through an experimental
      setup using laser techniques. These measurements were made of 18 knee joints used
      in KD prostheses. Lengthening of the thigh varied between 23 and 92 mm, and
      shortening of the shank varied between 3 and 50 mm. The polycentric knees Medi
      KH6 and Medi KHF1 showed the least lengthening of the thigh, and the polycentric
      knees Teh Lin Prosthetic & Orthotic Co. Ltd Graph-Lite and Medi KP5 showed the
      least shortening of the shank. 

PMID- 25856494
TI  - Moving stem cells to the clinic: potential and limitations for brain repair.
AB  - Stem cell-based therapies hold considerable promise for many currently
      devastating neurological disorders. Substantial progress has been made in the
      derivation of disease-relevant human donor cell populations. Behavioral data in
      relevant animal models of disease have demonstrated therapeutic efficacy for
      several cell-based approaches. Consequently, cGMP grade cell products are
      currently being developed for first in human clinical trials in select disorders.
      Despite the therapeutic promise, the presumed mechanism of action of donor cell
      populations often remains insufficiently validated. It depends greatly on the
      properties of the transplanted cell type and the underlying host pathology.
      Several new technologies have become available to probe mechanisms of action in
      real time and to manipulate in vivo cell function and integration to enhance
      therapeutic efficacy. Results from such studies generate crucial insight into the
      nature of brain repair that can be achieved today and push the boundaries of what
      may be possible in the future.

PMID- 25856501
TI  - Dehydration of blood platelets by zeodration: in vitro characterization and
      hemostatic properties in vivo.
AB  - BACKGROUND: Platelets (PLTs) are currently stored at room temperature (RT) for 5
      to 7 days. So far, there exists no validated method for the preparation and long
      term storage of dehydrated PLTs suitable for transfusion after rehydration. In
      this study, a desiccation process, zeodration, was applied to PLTs. STUDY DESIGN
      AND METHODS: A complete procedure of dehydration at RT by zeodration was
      employed. Zeodrated human and mouse PLTs were characterized in vitro. Zeodrated
      mouse PLTs were transfused into clopidogrel-treated mice to evaluate their
      hemostatic properties. RESULTS: The optimal conditions for dehydration of PLTs at
      RT in a laboratory scale zeodrator were defined as 145 mbar and 20.2 +/- 1.5 
      degrees C. The recovery rate was 85 +/- 2% and the dryness of zeodrated PLTs
      (Z_PLTs) indicated that they were sufficiently stable for long-term storage.
      Rehydrated Z_PLTs were round, were not aggregated, and expressed the
      glycoproteins required for PLT function. Z_PLTs agglutinated in the presence of
      von Willebrand factor (VWF) and aggregated in response to thrombin or collagen
      independently of an active metabolism. In a flow system, Z_PLTs could adhere to
      VWF and form aggregates on a collagen matrix. Thrombin was generated at the
      surface of Z_PLTs as efficiently as on fresh PLTs. In clopidogrel-treated mice,
      which exhibited a severely prolonged bleeding time, continuous perfusion of
      Z_PLTs restored normal hemostasis. CONCLUSION: Zeodration represents a new
      strategy to prepare PLTs with partly preserved aggregative properties after
      storage and rehydration. Z_PLTs have potential hemostatic properties provided it
      is possible to improve their transfusion efficacy.

PMID- 25856503
TI  - Combined heterogeneous distribution of salt and aroma in food enhances salt
      perception.
AB  - Aroma-taste interactions and heterogeneous spatial distribution of tastants were
      used as strategies for taste enhancement. This study investigated the combination
      of these two strategies through the effect of heterogeneous salt and aroma
      distribution on saltiness enhancement and consumer liking for hot snacks. Four
      layered cream-based products were designed with the same total amount of sodium
      and ham aroma but varied in their spatial distribution. Unflavoured products
      containing the same amount of salt and 35% more salt were used as references. A
      consumer panel (n = 82) rated the intensity of salty, sweet, sour, bitter and
      umami tastes as well as ham and cheese aroma intensity for each product. The
      consumers also rated their liking for the products in a dedicated sensory
      session. The results showed that adding salt-associated aroma (ham) led to
      enhancement of salty taste perception regardless of the spatial distribution of
      salt and aroma. Moreover, products with a higher heterogeneity of salt
      distribution were perceived as saltier (p < 0.01), whereas heterogeneity of ham
      aroma distribution had only a marginal effect on both aroma and salty taste
      perception. Furthermore, heterogeneous products were well liked by consumers
      compared to the homogeneous products. 

PMID- 25856504
TI  - Elevated plasma CXCL12alpha is associated with a poorer prognosis in pulmonary
      arterial hypertension.
AB  - RATIONALE: Recent work in preclinical models suggests that signalling via the pro
      angiogenic and pro-inflammatory cytokine, CXCL12 (SDF-1), plays an important
      pathogenic role in pulmonary hypertension (PH). The objective of this study was
      to establish whether circulating concentrations of CXCL12alpha were elevated in
      patients with PAH and related to mortality. METHODS: Plasma samples were
      collected from patients with idiopathic pulmonary arterial hypertension (IPAH)
      and PAH associated with connective tissue diseases (CTD-PAH) attending two
      pulmonary hypertension referral centres (n = 95) and from age and gender matched
      healthy controls (n = 44). Patients were subsequently monitored throughout a
      period of five years. RESULTS: CXCL12alpha concentrations were elevated in PAH
      groups compared to controls (P<0.05) and receiver-operating-characteristic
      analysis showed that plasma CXCL12alpha concentrations discriminated patients
      from healthy controls (AUC 0.80, 95% confidence interval 0.73-0.88). Kaplan Meier
      analysis indicated that elevated plasma CXCL12alpha concentration was associated
      with reduced survival (P<0.01). Multivariate Cox proportional hazards model
      showed that elevated CXCL12alpha independently predicted (P<0.05) earlier death
      in PAH with a hazard ratio (95% confidence interval) of 2.25 (1.01-5.00). In the
      largest subset by WHO functional class (Class 3, 65% of patients) elevated
      CXCL12alpha independently predicted (P<0.05) earlier death, hazard ratio 2.27
      (1.05-4.89). CONCLUSIONS: Our data show that elevated concentrations of
      circulating CXCL12alpha in PAH predicted poorer survival. Furthermore, elevated
      circulating CXCL12alpha was an independent risk factor for death that could
      potentially be included in a prognostic model and guide therapy.

PMID- 25856505
TI  - The two-component system CpxAR is essential for virulence in the phytopathogen
      bacteria Dickeya dadantii EC3937.
AB  - The CpxAR two-component system is present in many Proteobacteria. It controls
      expression of genes required to maintain envelope integrity in response to
      environmental injury. Consequently, this two-component system was shown to be
      required for virulence of several zoo-pathogens, but it has never been
      investigated in phyto-pathogens. In this paper, we investigate the role of the
      CpxAR two-component system in vitro and in vivo in Dickeya dadantii, an
      enterobacterial phytopathogen that causes soft-rot disease in a large variety of
      plant species. cpxA null mutant displays a constitutively phosphorylated CpxR
      phenotype as shown by direct analysis of phosphorylation of CpxR by a Phos-Tag
      retardation gel approach. Virulence in plants is completely abolished in cpxA or
      cpxR mutants of D. dadantii. In planta, CpxAR is only activated at an early stage
      of the infection process as shown by Phos-Tag and gene fusion analyses. To our
      knowledge, this is the first time that the timing of CpxAR phosphorelay
      activation has been investigated during the infection process by direct
      monitoring of response regulator phosphorylation. 

PMID- 25856502
TI  - Personalized biochemistry and biophysics.
AB  - Whole human genome sequencing of individuals is becoming rapid and inexpensive,
      enabling new strategies for using personal genome information to help diagnose,
      treat, and even prevent human disorders for which genetic variations are
      causative or are known to be risk factors. Many of the exploding number of newly
      discovered genetic variations alter the structure, function, dynamics, stability,
      and/or interactions of specific proteins and RNA molecules. Accordingly, there
      are a host of opportunities for biochemists and biophysicists to participate in
      (1) developing tools to allow accurate and sometimes medically actionable
      assessment of the potential pathogenicity of individual variations and (2)
      establishing the mechanistic linkage between pathogenic variations and their
      physiological consequences, providing a rational basis for treatment or
      preventive care. In this review, we provide an overview of these opportunities
      and their associated challenges in light of the current status of genomic science
      and personalized medicine, the latter often termed precision medicine. 

PMID- 25856507
TI  - Highlights in NSCLC from the 15th World Conference on Lung Cancer.

PMID- 25856506
TI  - Plasmonic eigenmodes in individual and bow-tie graphene nanotriangles.
AB  - In classical electrodynamics, nanostructured graphene is commonly modeled by the
      computationally demanding problem of a three-dimensional conducting film of
      atomic-scale thickness. Here, we propose an efficient alternative two-dimensional
      electrostatic approach where all calculation procedures are restricted to the
      graphene sheet. Furthermore, to explore possible quantum effects, we perform
      tight-binding calculations, adopting a random-phase approximation. We investigate
      multiple plasmon modes in 20 nm equilateral triangles of graphene, treating the
      optical response classically as well as quantum mechanically. Compared to the
      classical plasmonic spectrum which is "blind" to the edge termination, we find
      that the quantum plasmon frequencies exhibit blueshifts in the case of armchair
      edge termination of the underlying atomic lattice, while redshifts are found for
      zigzag edges. Furthermore, we find spectral features in the zigzag case which are
      associated with electronic edge states not present for armchair termination.
      Merging pairs of triangles into dimers, plasmon hybridization leads to energy
      splitting that appears strongest in classical calculations while splitting is
      lower for armchair edges and even more reduced for zigzag edges. Our various
      results illustrate a surprising phenomenon: Even 20 nm large graphene structures
      clearly exhibit quantum plasmonic features due to atomic-scale details in the
      edge termination. 

PMID- 25856508
TI  - Commentary: highlights in NSCLC from the 15th World Conference on Lung Cancer.

PMID- 25856509
TI  - Synthesis toward CRHR1 Antagonists through 2,7-Dimethylpyrazolo[1,5
      alpha][1,3,5]triazin-4(3H)-one C-H Arylation.
AB  - A novel synthetic protocol for 8-aryl substituted pyrazolo[1,5
      alpha][1,3,5]triazin-4(3H)-ones was developed employing Pd-catalyzed C-H
      arylation. The reaction yield was influenced by the presence of a phosphine
      ligand, pivalic acid, and base selection. With the use of 5-10 mol % catalyst,
      reactions of 2 with p- or m-substituted aryl bromides proceeded in moderate to
      good yields. Lower yields were observed with o-substituted aryl bromides. Using
      this method a precursor for MJL1-109-2, a known nonpeptide CRHR-1 antagonist, was
      successfully synthesized. 

PMID- 25856510
TI  - Facile net cycloaddition approach to optically active 1,5-benzothiazepines.
AB  - The 1,5-benzothiazepine moiety is well-known as a versatile pharmacophore, and
      its derivatives are expected to have antagonism against numerous diseases. Thus,
      it is desirable to develop a synthetic route that enables facile enantioselective
      preparation of a wide range of such derivatives. Although the cycloaddition
      approach could be considered a possible route to these compounds, to date, there
      has been no precedent of such a protocol. We therefore present the first example
      of a highly enantioselective net [4 + 3] cycloaddition to afford 1,5
      benzothiazepines by utilizing alpha,beta-unsaturated acylammonium intermediates
      generated by chiral isothiourea catalysts, which undergo two sequential
      chemoselective nucleophilic attacks by 2-aminothiophenols. This protocol provided
      cycloadducts in extremely high regioselectivity, with a good-to-excellent
      stereoselectivity being achieved regardless of the steric and electronic
      properties of the substrates. This method therefore offers promising synthetic
      routes for the construction of a library of optically active 1,5-benzothiazepines
      for assay evaluation. 

PMID- 25856511
TI  - Prototype positron emission tomography insert with electro-optical signal
      transmission for simultaneous operation with MRI.
AB  - The simultaneous acquisition of PET and MRI data shows promise to provide
      powerful capabilities to study disease processes in human subjects, guide the
      development of novel treatments, and monitor therapy response and disease
      progression. A brain-size PET detector ring insert for an MRI system is being
      developed that, if successful, can be inserted into any existing MRI system to
      enable simultaneous PET and MRI images of the brain to be acquired without mutual
      interference. The PET insert uses electro-optical coupling to relay all the
      signals from the PET detectors out of the MRI system using analog modulated
      lasers coupled to fiber optics. Because the fibers use light instead of
      electrical signals, the PET detector can be electrically decoupled from the MRI
      making it partially transmissive to the RF field of the MRI. The SiPM devices and
      low power lasers were powered using non-magnetic MRI compatible batteries. Also,
      the number of laser-fiber channels in the system was reduced using techniques
      adapted from the field of compressed sensing. Using the fact that incoming PET
      data is sparse in time and space, electronic circuits implementing constant
      weight codes uniquely encode the detector signals in order to reduce the number
      of electro-optical readout channels by 8-fold. Two out of a total of sixteen
      electro-optical detector modules have been built and tested with the entire RF
      shielded detector gantry for the PET ring insert. The two detectors have been
      tested outside and inside of a 3T MRI system to study mutual interference effects
      and simultaneous performance with MRI. Preliminary results show that the PET
      insert is feasible for high resolution simultaneous PET/MRI imaging for
      applications in the brain.

PMID- 25856513
TI  - Density functional theory study of Rh(III)-catalyzed C-H activations and
      intermolecular annulations between benzamide derivatives and allenes.
AB  - Density functional theory has been applied to gain insight into the Cp*Rh(OAc)2
      catalyzed C-H activation and intermolecular annulation of benzamide derivatives
      with allenes. The study shows that the reactions proceed in three steps: (1) C-H
      activation induced by Rh catalyst reacting with benzamide derivatives, (2)
      carborhodation of allene, and (3) regeneration of Rh catalyst. The results
      indicate that the N-H deprotonation makes the following C-H activation much
      easier. The regio- and stereoselectivities of 1a (N-pivaloyloxy benzamide)/2a
      (cyclohexylallene) and 1b (N-pivaloyloxy-4-methyl-benzamide)/2b (1,1-dimethyl
      allene) depend on the allene carborhodation step. The steric hindrance effect is
      the dominant factor. We also discuss the reaction mechanism of 1c (N-methoxy
      benzamide)/2a. The chemoselectivity between 1c/2a is determined by the N-O
      cleavage step. Replacement of OPiv by OMe leads to loss of the stabilization
      effect provided by C=O in OPiv. Additionally, Cp*Rh(OAc)(OPiv) is produced in the
      Cp*Rh(OAc)2 regeneration step, which can work as catalyst as well.

PMID- 25856512
TI  - Genetic variants of SLC11A1 are associated with both autoimmune and infectious
      diseases: systematic review and meta-analysis.
AB  - A systematic review and meta-analyses were undertaken to investigate the
      association of SLC11A1 genetic variants with disease occurrence. Literature
      searching indentified 109 publications to include in the meta-analyses assessing
      the association of 11 SLC11A1 variants with autoimmune and infectious disease.
      The (GT)n promoter alleles 2 and 3 (rs534448891), which alter SLC11A1 expression,
      were significantly associated with tuberculosis (OR=1.47 (1.30-1.66), OR=0.76
      (0.65-0.89), respectively) and infectious disease (OR=1.25 (1.10-1.42), OR=0.83
      (0.74-0.93), respectively). However, although no association was observed with
      autoimmune disease, a modest significant association was observed with type 1
      diabetes (allele 2 OR=0.94 (0.89-0.98)). On the basis of a stronger association
      of (GT)n allele 2 with tuberculosis, compared with the protective effect of
      allele 3, we hypothesise that allele 2 is likely the disease-causing variant
      influencing disease susceptibility. Significant associations were observed
      between the 469+14G/C polymorphism (rs3731865) and autoimmune disease (OR=1.30
      (1.04-1.64)) and rheumatoid arthritis (OR=1.60 (1.20-2.13)) and between the 
      237C/T polymorphism (rs7573065) and inflammatory bowel disease (OR=0.60 (0.43
      0.84)). Further, significant associations were identified between the 469+14G/C,
      1730G/A and 1729+55del4 polymorphisms (rs3731865, rs17235409 and rs17235416,
      respectively) and both infectious disease per se and tuberculosis. These findings
      show a clear association between variants in the SLC11A1 locus and autoimmune and
      infectious disease susceptibility. 

PMID- 25856514
TI  - A rhodamine-based 'turn-on' Al3+ ion-selective reporter and the resultant complex
      as a secondary sensor for F- ion are applicable to living cell staining.
AB  - A newly designed fluorescent aluminum(III) complex (L'-Al; 2) of a structurally
      characterized non-fluorescent rhodamine Schiff base (L) has been isolated in pure
      form and characterized using spectroscopic and physico-chemical methods with
      theoretical density functional theory (DFT) support. On addition of Al(III) ions
      to a solution of L in HEPES buffer (1 mM, pH 7.4; EtOH-water, 1 : 3 v/v) at 25 
      degrees C, the systematic increase in chelation-enhanced fluorescence (CHEF)
      enables the detection of Al(III) ions as low as 60 nM with high selectivity,
      unaffected by the presence of competitive ions. Interestingly, the Al(III)
      complex (L'-Al; 2) is specifically able to detect fluoride ions by quenching the
      fluorescence in the presence of large amounts of other anions in the HEPES buffer
      (1 mM, pH 7.4) at 25  degrees C. On the basis of our experimental and theoretical
      findings, the addition of Al(3+) ions to a solution of L helps to generate a new
      fluorescence peak at 590 nm, due to the selective binding of Al(3+) ions with L
      in a 1 : 1 ratio with a binding constant (K) of 8.13 * 10(4) M(-1). The Schiff
      base L shows no cytotoxic effect, and it can therefore be employed for
      determining the intracellular concentration of Al(3+) and F(-) ions by 2 in
      living cells using fluorescence microscopy.

PMID- 25856515
TI  - Determination of the complete mitogenome of Spotted Dove, Spilopelia chinensis
      (Columbiformes: Columbidae).
AB  - The Spotted Dove Spilopelia chinensis (Columbiformes: Columbidae) is widely
      distributed in Southeast Asia. In the present study, we investigated the complete
      mitochondrial genome of S. chinensis and the mitogenome is 16,964 bp in length,
      consists of 13 protein-coding genes, 22 transfer RNA genes, two ribosomal RNA
      genes, and a non-coding control region, with the base composition of A 31.1%, G
      13.9%, T 23.9%, and C 32.1%. A single extra base "C" at position 174 is inserted
      in gene Nd3, similar to some other birds and turtles. The phylogenetic
      relationships using partitioned Bayesian inference based on the 12 concatenated
      PCGs indicated that ((((Spilopelia, Columba) Ectopistes) (Geotrygon (Leptotila,
      Zenaida))) Hemiphaga). While, more complete mitogenome sequences should be
      determined to confirm the phylogenetic status of Spilopelia within family
      Columbidae.

PMID- 25856516
TI  - The near-complete mitogenome sequence of the Omei Horned Toad Megophrys
      omeimontis Liu, 1950 (Anura, Megophryidae).
AB  - The nearly complete mitogenome of Megophrys omeimontis is 17,013 bp in length,
      including 13 protein-coding genes (PCGs), 2 rRNA genes, 22 tRNA genes and a D
      loop region, and it shares the identical gene arrangement with Atympanophrys
      shapingensis. The overall base composition of this mitogenome is biased toward AT
      content at 60.10%. Most PCGs begin with ATG, whereas ND1 starts with ATA, ND2
      initiates from ATT, ND3 starts with ATC, and COX1 begins with GTG. Four PCGs
      (COX1, ATP8, ND4L and ND5) use complete stop codon TAR, and ND6 ends with AGG,
      but the remaining eight PCGs terminate in TA or T. The putative control region of
      M. omeimontis mitogenome holds two tandem repeat motifs at the 5' and 3' ends,
      which is different from that of A. shapingensis mtDNA. Megophrys omeimontis
      becomes the sister lineage to the two other species, B. carinense and A.
      shapingensis.

PMID- 25856517
TI  - Characterization of the mitochondrial genome of Bufo gargarizans minshanicus
      (Anura: Bufonidae).
AB  - The complete mitogenome of Bufo gargarizans minshanicus is 17,719 bp in size, and
      shares a conserved gene arrangement, gene content and base composition with other
      Bufonidae species. The base composition of the H-strand is biased toward A + T
      content at 56.97% (T 28.14%, C 27.67%, A 28.83% and G 15.36%). Most protein
      coding genes (PCGs) begin with ATG, while COX1 and ND2 initiate with ATA and ND1
      starts at ATT. Seven PCGs have the complete stop codons AGA and TAA, whereas the
      remaining four PCGs end with TA or T. The putative control region possesses two
      repeat motifs, and four termination-associated sequences and six conserved
      sequence blocks at the 5' and 3' ends.

PMID- 25856518
TI  - The complete chloroplast genome sequence of the medicinal plant Andrographis
      paniculata.
AB  - The complete chloroplast genome of Andrographis paniculata, an important
      medicinal plant with great economic value, has been studied in this article. The
      genome size is 150,249 bp in length, with 38.3% GC content. A pair of inverted
      repeats (IRs, 25,300 bp) are separated by a large single copy region (LSC, 82,459
      bp) and a small single-copy region (SSC, 17,190 bp). The chloroplast genome
      contains 114 unique genes, 80 protein-coding genes, 30 tRNA genes and 4 rRNA
      genes. In these genes, 15 genes contained 1 intron and 3 genes comprised of 2
      introns.

PMID- 25856519
TI  - Role of the unfolded protein response in the pathogenesis of Parkinson's disease.
AB  - Parkinson's disease is the second most common neurodegenerative disease which
      affects almost 1 percent of the population above the age of 60. It is is
      characterized by loss of dopaminergic neurons in the striatum and substantia
      nigra, coupled with the formation of intracellular Lewy bodies in degenerating
      neurons. Recent evidence suggests endoplasmic reticulum stress as a common and
      prominent occurrence in the progression of Parkinson's disease pathogenesis in
      the affected human brain. One of the cellular defense mechanism to combat
      endoplasmic reticulum stress due to excessive protein accumulation is through
      activation of the unfolded protein response pathway. In this review we focus on
      the impact and role of this unfolded protein response as a causative factor of
      Parkinson's disease leading to neurodegeneration. 

PMID- 25856520
TI  - Electrophysiology of GABAergic transmission of single intergeniculate leaflet
      neurons in rat.
AB  - The intergeniculate leaflet (IGL) of the thalamus constitutes a small but
      important part of the neural network controlling circadian activity in rodents.
      It appears that IGL integrates photic cues from retina with non-photic
      information originating from different nonspecific brain systems. Subsequently,
      this integrated signal is passed to the master biological clock - the
      suprachiasmatic nuclei (SCN). The common neurotransmitter of biological clock
      neural structures, the gamma-amino-butyric acid (GABA) is expressed in many, if
      not all, IGL and SCN neurons. Whole-cell patch clamp in vitro
      electrophysiological experiments were performed in order to evaluate GABA's
      influence on single IGL neurons in rat. Most neurons were hyperpolarized by GABA
      application and this effect was caused by activation of GABAA as well as GABAB
      receptors. The presence of GABAB receptors in rat's IGL has been suggested for
      the first time.

PMID- 25856521
TI  - RNAi mediated silencing of cyclin-dependent kinases of G1 phase slows down the
      cell-cycle progression and reduces apoptosis.
AB  - One of the hypotheses on the origin of Alzheimer's disease (AD) stems from a
      close relation between a re-activation of a cell-cycle in post-mitotic neurons
      and a neural cells death observed in pathologically affected parts of AD brains.
      In the normal, healthy brain almost all neural cells are terminally
      differentiated and "locked" in the G0 phase of the cell-cycle. For these cells,
      the consequence of the re-entry to the cell-cycle is targeting them towards
      cellular divisions and turning on the apoptotic pathway. We used an RNA
      interference (RNAi) methodology in neural cells to switch-off genes for two
      cyclindependent kinases 4 and 6 (cdk4, cdk6), which control the activation of the
      initial steps of the cell-cycle. As a result, some evidences are delivered that
      silencing these genes, which are expressed during cell proliferation but
      inhibited at mature neurons, prevents the stimulation of apoptotic pathways in
      the neural cells cultured in a oxidative stress conditions and may have a
      neuroprotective effect. We demonstrate that down-regulation of genes important in
      the G1 phase of the cell-cycle may play the protective function on the neuronal
      cells, and can be considered as the promising approach for the potential gene
      therapy of neurodegenerative diseases.

PMID- 25856522
TI  - Hippocampal asymmetry in angiotensin II modulatory effects on learning and memory
      in rats.
AB  - Learning and memory effects of angiotensin II (Ang II) microinjected unilaterally
      (left or right) and bilaterally into hippocampal CA1 area on the background of
      the inhibited hippocampal angiotensin 1 receptors type (AT1) of male Wistar rats
      were studied. It was found that the combination (losartan 100 micrograms + Ang II
      0.5 micrograms) microinjected bilaterally or into the left CA1 area improved
      learning and memory in shuttle-box and step through behavioral tests as compared
      to the respective controls. The effects were more pronounced after injection into
      the left CA1 area as compared to the right-side. These findings suggest that Ang
      II infused on the background of the inhibited CA1 hippocampal AT1 receptors
      ameliorated the cognitive processes. The data show also an asymmetric effect of
      Ang II on learning and memory processes in the hippocampus. The stronger
      modulating effect after microinjection of the combination (losartan + Ang II)
      into the left CA1 hippocampal area suggests a leftward bias in the rat. The
      results point to a differential distribution of angiotensin II receptors
      modulating the learning and memory processes in the left and right hippocampal
      CA1 area.

PMID- 25856523
TI  - Signals mediating Klotho-induced neuroprotection in hippocampal neuronal cells.
AB  - The erythropoietin (Epo) receptor (EpoR) is expressed in the brain and was shown
      to have neuroprotective effects against brain damage in animal models. A recent
      study indicated that EpoR and its activity are the downstream effectors of Klotho
      for cytoprotection in the kidney. Thus, we propose that Klotho can stimulate the
      expression of EpoR in neuronal cells to enhance Epo-mediated protection. H19-7
      hippocampal neuronal cells were treated with recombinant Klotho. In H19-7 cells,
      Klotho increased the expression of both the EpoR protein and mRNA. Klotho also
      enhanced the transcription activity of the EpoR promoter in H19-7 cells.
      Moreover, Klotho augmented the Epo-triggered phosphorylation of Jak2 and Stat5
      and protected H19-7 cells from hydrogen peroxide cytotoxicity. The silencing of
      EpoR abolished the protective effect of Klotho against peroxide-induced
      cytotoxicity. Finally, the silencing of GATA1 diminished the Klotho-induced
      increase in EpoR protein and mRNA expression as well as its promoter activity. In
      conclusion, Klotho increased EpoR expression in neuronal cells through GATA1,
      thereby enabling EpoR to function as a cytoprotective protein against oxidative
      injury.

PMID- 25856524
TI  - Effects of post-weaning social isolation and environment al enrichment on
      exploratory behavior and ankiety in Wistar rats.
AB  - Adverse early experience is generally regarded as a risk factor for both
      externalizing and internalizing behavioral disorders in humans. It can be modeled
      in rats by a post-weaning social isolation procedure. Effects of social isolation
      might possibly be ameliorated by environmental enrichment. In the current study,
      24 male Wistar rats were divided post-weaning into four rearing conditions:
      control, environmental enrichment (EE), social isolation (SI) and a combination
      of the two experimental conditions; (EE+SI). Two observations of the effects of
      rearing conditions on the rate of social and object interactions were conducted
      during the juvenile and post-pubertal stages of development. The SI condition led
      to a marked increase of social interactions during the juvenile phase, but did
      not affect object interactions. The EE condition increased the level of social
      interactions during both the juvenile and post-pubertal measurements. The effects
      of early rearing conditions on adult exploratory behavior were less clear, with a
      significant difference between the groups obtained in one of three behavioral
      tests. Results suggest a general robustness in the development of adult
      exploratory behavior and anxiety when rats were exposed to early social isolation
      and provided brief opportunities for social play during the juvenile period.
      Further studies, aimed at distinguishing play-related protective factors serving
      against long-term adverse effects of juvenile social isolation, are suggested.

PMID- 25856525
TI  - The role of phonological awareness in treatments of dyslexic primary school
      children.
AB  - The present study investigated whether phonological awareness training is an
      effective intervention to significantly improve reading in German dyslexic third
      and fourth graders with a phonological awareness deficit, and whether these
      children can equally benefit from a phonology-based reading training or a
      visually-based reading training. German speaking dyslexic elementary school
      children (n=30; M=9.8 years) were matched by forming triplets based on IQ,
      reading quotient and phonological awareness and then randomly assigned to one out
      of three interventions (n=10): a phonological awareness training, a phonology
      based reading training (phonics instruction), and a visually-based reading
      training (repeated reading of sight words). A total of 20 training sessions (30
      minutes each) were distributed over four weeks. Typical readers (n=10; M=9.5
      years) were assigned to the control group. Phonological awareness training
      directly improves reading comprehension in German dyslexic children with a
      phonological awareness deficit. However, these children can equally benefit from
      a visually-based reading training. In contrast, the phonology-based reading
      training has a direct selective effect on decoding but not on reading
      comprehension. Despite divergent short-term patterns, long-term improvement of
      reading comprehension and decoding is similar across all training groups,
      irrespective of the training method. Phonological awareness may but does not need
      to be part of reading remediation in dyslexic children with a phonological
      deficit when learning to read a consistent orthography. Rather, a visually-based
      reading strategy might compensate for the phonological deficit in dyslexic
      children after the initial stage of reading acquisition.

PMID- 25856526
TI  - Comparison of dynamic behavior and maturation of neural multipotent cells derived
      from different spinal cord developmental stages: an in vitro study.
AB  - Neural progenitor cells (NPCs) are characterized as undifferentiated cells with
      the ability of self-renewal and multipotency to give rise to other cells of the
      nervous system. In our in vitro study we demonstrate the proliferative and
      differentiative potential of NPCs isolated from the spinal cord at different
      developmental stages (embryonal, early postnatal, adult), maintained and expanded
      within neurospheres (NSs). Using the NSs culture system, we examined the size,
      number of NSs and their fate when exposed to differentiation conditions. Based on
      immunocytochemical analyses for cell markers (MAP 2, GFAP, RIP) we evaluated the
      occurrence of various cell types: neurons, astrocytes and oligodendrocytes. The
      results show that NSs increased in size during cultivation time via NPC
      proliferation, but proliferation potential decreased Turing maturation stages. In
      addition, NPCs derived from spinal cord developmentally different stages gave
      rise to a consistent ratio of glial and neuronal progeny (3:1), and adult tissues
      represent a comparable source of NPCs compared to embryonal and early postnatal
      tissues. These data provide useful information for large-scale in vitro expansion
      of NPCs required for potential cell therapy after spinal cord injury.

PMID- 25856527
TI  - Comment on: Applying extender devices in patients with penile dysmorphophobia:
      assessment of tolerability, efficacy, and impact on erectile function.

PMID- 25856528
TI  - Bacterial Recombineering: Genome Engineering via Phage-Based Homologous
      Recombination.
AB  - The ability to specifically modify bacterial genomes in a precise and efficient
      manner is highly desired in various fields, ranging from molecular genetics to
      metabolic engineering and synthetic biology. Much has changed from the initial
      realization that phage-derived genes may be employed for such tasks to today,
      where recombineering enables complex genetic edits within a genome or a
      population. Here, we review the major developments leading to recombineering
      becoming the method of choice for in situ bacterial genome editing while
      highlighting the various applications of recombineering in pushing the boundaries
      of synthetic biology. We also present the current understanding of the mechanism
      of recombineering. Finally, we discuss in detail issues surrounding
      recombineering efficiency and future directions for recombineering-based genome
      editing. 

PMID- 25856529
TI  - Association between alcohol consumption and pancreatic cancer risk: a case
      control study.
AB  - PURPOSE: Evidence is inconsistent regarding alcohol and pancreatic cancer risk,
      although heavy drinking may increase risk. METHODS: A population-based case
      control study was conducted using 345 pancreas cancer cases diagnosed 2011-2012
      and 1,285 frequency-matched controls from Ontario, Canada. Logistic regression
      was used to evaluate alcohol consumption and pancreatic cancer risk; data was
      also stratified by sex and smoking status to assess interaction. RESULTS: Alcohol
      consumption was not associated with pancreatic cancer risk (age-adjusted odds
      ratio=0.78, 95% CI: 0.58, 1.05 for 1 - 3 drinks/week; age-adjusted odds
      ratio=0.86, 95% CI: 0.63, 1.17 for 4 - 20 drinks/week), however there was a non
      significant increased risk for heavy drinkers consuming >= 21 drinks/week (age
      adjusted odds ratio=1.35, 95% CI: 0.81, 2.27). Cigarette smoking modified the
      alcohol-cancer relationship; among current smokers, heavy alcohol consumption was
      associated with a significantly increased pancreatic cancer risk (age-adjusted
      odds ratio=4.04, 95% CI: 1.58, 10.37), whereas this significant association with
      heavy drinking was not observed among non-smokers (age-adjusted odds ratio=2.01,
      95% CI: 0.50, 8.18). Furthermore, light - moderate alcohol intake was associated
      with increased pancreas cancer risk among current smokers. CONCLUSIONS: While
      alcohol was not significantly associated with pancreatic cancer risk, smoking
      status modified this relationship such that among current smokers, alcohol intake
      was associated with a greater than two-fold increased risk of pancreatic cancer.
      The results should be interpreted with caution due to small sample sizes within
      subgroups and correction for multiple comparisons should be considered. These
      findings should be replicated in larger studies where more precise estimates of
      risk can be obtained.

PMID- 25856530
TI  - Improving behavior using child-directed interaction skills: A case study
      determining cochlear implant candidacy.
AB  - OBJECTIVE AND IMPORTANCE: Children with hearing loss (HL) are at increased risk
      of developing externalizing behavior problems (e.g., hyperactivity, attention
      problems). These problems can lead to cascading effects on children's overall
      development. However, few studies have identified evidence-based interventions
      for this population. CLINICAL PRESENTATION: A 6-year-old boy with bilateral HL
      presented to the clinic with significant behavioral challenges. These challenges
      (e.g., fatigued quickly, poor attention, and hyperactivity) were affecting the
      reliability of audiological testing to determine cochlear implant candidacy.
      Thus, the child was referred for Parent-Child Interaction Therapy (PCIT) to
      address these behavioral challenges. INTERVENTION AND TECHNIQUE: PCIT is an
      evidence-based intervention that has been shown to significantly improve
      externalizing behavior problems. This study describes how the Child-Directed
      Interaction phase of PCIT was tailored for a child with bilateral HL. The goal of
      the intervention was to reduce externalizing behaviors in order to reliably
      complete a cochlear implant evaluation. Post-intervention, significant
      improvements were noted in behavior, including a decrease in disruptive behavior
      to normal levels. This led to completion of previously unsuccessful audiological
      testing and determination of cochlear implant candidacy. CONCLUSION: This study
      illustrates how PCIT was successfully tailored to one child with an HL. This is
      critical as children with HL are at risk for behavior problems, and effective
      interventions for disruptive behaviors in children with HL may lead to
      significant improvements in medical and psychosocial outcomes for children with
      HL and their families.

PMID- 25856531
TI  - Antiarrhythmic Mechanisms of SK Channel Inhibition in the Rat Atrium.
AB  - INTRODUCTION: SK channels have functional importance in the cardiac atrium of
      many species, including humans. Pharmacological blockage of SK channels has been
      reported to be antiarrhythmic in animal models of atrial fibrillation; however,
      the exact antiarrhythmic mechanism of SK channel inhibition remains unclear.
      OBJECTIVES: We speculated that together with a direct inhibition of repolarizing
      SK current, the previously observed depolarization of the atrial resting membrane
      potential (RMP) after SK channel inhibition reduces sodium channel availability,
      thereby prolonging the effective refractory period and slowing the conduction
      velocity (CV). We therefore aimed at elucidating these properties of SK channel
      inhibition and the underlying antiarrhythmic mechanisms using microelectrode
      action potential (AP) recordings and CV measurements in isolated rat atrium.
      Automated patch clamping and two-electrode voltage clamp were used to access INa
      and IK,ACh, respectively. RESULTS: The SK channel inhibitor N-(pyridin-2-yl)-4
      (pyridin-2-yl)thiazol-2-amine (ICA) exhibited antiarrhythmic effects. ICA
      prevented electrically induced runs of atrial fibrillation in the isolated right
      atrium and induced atrial postrepolarization refractoriness and depolarized RMP.
      Moreover, ICA (1-10 MUM) was found to slow CV; however, because of a marked
      prolongation of effective refractory period, the calculated wavelength was
      increased. Furthermore, at increased pacing frequencies, SK channel inhibition by
      ICA (10-30 MUM) demonstrated prominent depression of other sodium channel
      dependent parameters. ICA did not inhibit IK,ACh, but at concentrations above 10
      MUM, ICA use dependently inhibited INa. CONCLUSIONS: SK channel inhibition
      modulates multiple parameters of AP. It prolongs the AP duration and shifts the
      RMP towards more depolarized potentials through direct ISK block. This indirectly
      leads to sodium channel inhibition through accumulation of state dependently
      inactivated channels, which ultimately slows conduction and decreases
      excitability. However, a contribution from a direct sodium channel inhibition
      cannot be ruled. We here propose that the primary antiarrhythmic mechanism of SK
      channel inhibition is through direct potassium channel block and through indirect
      sodium channel inhibition.

PMID- 25856532
TI  - Acute chemical incidents surveillance-Hazardous Substances Emergency Events
      Surveillance, nine states, 1999-2008.
AB  - PROBLEM/CONDITION: Although they are infrequent, acute chemical incidents (i.e.,
      uncontrolled or illegal release or threatened release of hazardous substances
      lasting <72 hours) with mass casualties or extraordinary levels of damage or
      disruption severely affecting the population, infrastructure, environment, and
      economy occur, and thousands of less damaging chemical incidents occur annually.
      Surveillance data enable public health and safety professionals to better
      understand the patterns and causes of these incidents, which can improve
      prevention efforts and preparation for future incidents. REPORTING PERIOD: 1999
      2008. DESCRIPTION OF SYSTEM: The Hazardous Substances Emergency Events
      Surveillance (HSEES) system was operated by the Agency for Toxic Substances and
      Disease Registry (ATSDR) during January 1991-September 2009 to describe the
      public health consequences of chemical releases and to develop activities aimed
      at reducing the harm. This report provides a historical overview of HSEES and
      summarizes incidents from the nine states (Colorado, Iowa, Minnesota, New York,
      North Carolina, Oregon, Texas, Washington, and Wisconsin) that participated in
      HSEES during its last 10 full years of data collection (1999-2008). RESULTS:
      During 1999-2008, a total of 57,975 chemical incidents occurred: 41,993 (72%)
      occurred at fixed facilities, and 15,981 (28%) were transportation related.
      Chemical manufacturing (NAICS 325) (23%) was the industry with the most
      incidents; however, the number of chemical incidents in chemical manufacturing
      decreased substantially over time (R2 = 0.78), whereas the educational services
      category (R2 = 0.65) and crop production category (R2 = 0.61) had a consistently
      increasing trend. The most common contributing factors for an incident were
      equipment failure (n = 22,535, 48% of incidents) and human error (n = 16,534,
      36%). The most frequently released chemical was ammonia 3,366 (6%). Almost 60% of
      all incidents occurred in two states, Texas and New York. A decreasing trend
      occurred in the number of incidents in Texas, Wisconsin, and Colorado, and an
      increasing trend occurred in Minnesota. INTERPRETATION: Although chemical
      manufacturing accounted for the largest percentage of incidents in HSEES, the
      number of chemical incidents over time decreased substantially for this industry
      while heightened awareness and prevention measures were being implemented.
      However, incidents in educational services and crop production settings
      increased. Trends in incidents and number of incidents varied by state. Only a
      certain few chemicals, sectors, and areas were found to be related to the
      majority of incidents and injured persons. Equipment failure and human error,
      both common casual factors, are preventable. PUBLIC HEALTH IMPLICATIONS: The
      findings in this collection of surveillance summaries underscore the need for
      educational institutions and the general public to receive more focused outreach.
      In addition, the select few chemicals and industries that result in numerous
      incidents can be the focus of prevention activities. The data in these
      surveillance summaries show that equipment maintenance, as well as training to
      prevent human error, could alleviate many of the incidents; NTSIP has begun work
      in these areas. State surveillance allows a state to identify its problem areas
      and industries and chemicals for prevention and preparedness. Beginning in 2010,
      ATSDR replaced HSEES with the National Toxic Substance Incidents Program (NTSIP)
      to expand on the work of HSEES. NTSIP helps states to collect surveillance data
      and to promote cost-effective, proactive measures such as converting to an
      inherently safer design, developing geographic mapping of chemically vulnerable
      areas, and adopting the principles of green chemistry (design of chemical
      products and processes that reduce or eliminate the generation of hazardous
      substances). Because the more populous states such as New York and Texas had the
      most incidents, areas with high population density should be carefully assessed
      for preparedness and prevention measures. NTSIP develops estimated incident
      numbers for states that do not collect data to help with state and national
      planning. NTSIP also collects more detailed data on chemical incidents with mass
      casualties. HSEES and NTSIP data can be used by public and environmental health
      and safety practitioners, worker representatives, emergency planners,
      preparedness coordinators, industries, emergency responders, and others to
      prepare for and prevent chemical incidents and injuries.

PMID- 25856533
TI  - Temporal trends of acute chemical incidents and injuries-Hazardous Substances
      Emergency Events Surveillance, nine states, 1999-2008.
AB  - PROBLEM/CONDITION: Widespread use of hazardous chemicals in the United States is
      associated with unintentional acute chemical incidents (i.e., uncontrolled or
      illegal release or threatened release of hazardous substances lasting <72 hours).
      Efforts by industries, government agencies, academics, and others aim to reduce
      chemical incidents and the public health consequences, environmental damage, and
      economic losses; however, incidents are still prevalent. REPORTING PERIOD: 1999
      2008. DESCRIPTION OF SYSTEM: The Hazardous Substances Emergency Events
      Surveillance (HSEES) system was operated by the Agency for Toxic Substances and
      Disease Registry (ATSDR) during January 1991-September 2009 to describe the
      public health consequences of chemical releases and to develop activities aimed
      at reducing the harm. This report summarizes temporal trends in the numbers of
      incidents, injured persons, deaths, and evacuations from the nine states
      (Colorado, Iowa, Minnesota, New York, North Carolina, Oregon, Texas, Washington,
      and Wisconsin) that participated in HSEES during its last 10 full years of data
      collection (1999-2008). RESULTS: A total of 57,975 incidents and 15,506 injured
      persons, including 354 deaths, were reported. During the surveillance period,
      several trends were observed: a slight overall decrease occurred in incidents for
      fixed facilities (R2 = 0.6) and an increasing trend in deaths (R2 = 0.7)
      occurred, particularly for the general public (R2 = 0.9). The number of incidents
      increased in the spring during March-June, and a decrease occurred in the
      remainder of the year (R2 = 0.5). A decreasing trend in incidents occurred during
      Monday-Sunday (R2 = 0.7) that was similar to that for the number of injured
      persons (R2 = 0.6). The highest number of incidents occurred earlier in the day
      (6:00 a.m.-11:59 a.m.) and then decreased as the day went on (R2 = 0.9); this
      trend was similar for the number of injured persons (R2 = 1.0). INTERPRETATION:
      Chemical incidents continue to affect public health and appear to be a growing
      problem for the general public. The number of incidents and injuries varied by
      month, day of week, and time of day and likely was influenced by other factors
      such as weather and the economy. PUBLIC HEALTH IMPLICATIONS: Public and
      environmental health and safety practitioners, worker representatives, emergency
      planners, preparedness coordinators, industries, emergency responders, and others
      can use the findings in this report to prepare for and prevent chemical incidents
      and injuries. Specifically, knowing when to expect the most incidents and
      injuries can guide preparedness and prevention efforts. In addition, new or
      expanded efforts and outreach to educate consumers who could be exposed to
      chemicals are needed (e.g., education about the dangers of carbon monoxide
      poisoning for consumers in areas likely to experience weather-related power
      outages). Redirection of efforts such as promoting inherently safer technologies
      should be explored to reduce or eliminate the hazards completely.

PMID- 25856534
TI  - Persons injured during acute chemical incidents-Hazardous Substances Emergency
      Events Surveillance, nine states, 1999-2008.
AB  - PROBLEM/CONDITION: Persons exposed to chemicals during acute chemical incidents
      (i.e., uncontrolled or illegal release or threatened release of hazardous
      substances lasting <72 hours) can experience both acute and chronic health
      effects. Surveillance of toxic substance incidents provides data that can be used
      to prevent future incidents and improve the emergency response to those that
      occur, leading to a decrease in morbidity and mortality from chemical releases.
      REPORTING PERIOD: 1999-2008 DESCRIPTION OF SYSTEM: The Hazardous Substances
      Emergency Events Surveillance (HSEES) system was operated by the Agency for Toxic
      Substances and Disease Registry (ATSDR) during January 1991-September 2009 to
      describe the public health consequences of chemical releases and to develop
      activities aimed at reducing the harm. This report summarizes the data collected
      on injured persons from the nine states (Colorado, Iowa, Minnesota, New York,
      North Carolina, Oregon, Texas, Washington, and Wisconsin) that participated in
      HSEES during its last 10 full years of data collection (1999-2008). RESULTS: A
      total of 57,975 chemical incidents were reported by these states during the 10
      year surveillance period. In 4,621 (8%) of these incidents, 15,506 persons were
      injured. Among them, 354 deaths occurred. The most commonly reported category of
      injured persons included employees of the responsible party (7,616 [49%]),
      members of the general public (4,737 [31%]), students exposed at school (1,730
      [11%]), and responders to the incident (1,398 [9%]). Deaths occurred among
      members of the general public (190 [54%]), employees (154 [44%]), and responders
      (10 [3%]). The most frequent health effects experienced as a result of these
      incidents included respiratory irritation (7,443), dizziness or central nervous
      system problems (3,186), and headache (3,167). The three chemicals associated
      with the largest number of persons injured were carbon monoxide (2,364), ammonia
      (1,153), and chlorine (763). INTERPRETATION: Company employees, followed by
      members of the general public, are frequently injured in acute chemical
      incidents. The chemicals most often associated with these injuries are carbon
      monoxide, ammonia, and chlorine, all of which are hazardous gases that can be
      found in various locations including schools and homes. Respiratory irritation is
      the most common health effect. PUBLIC HEALTH IMPLICATIONS: By understanding the
      types of persons injured in chemical release incidents, as well as how they are
      injured and the injuries sustained, prevention outreach activities can be focused
      to protect the health of these groups in the future. Improved awareness among and
      training for not just employees but also the public is needed, particularly
      regarding carbon monoxide, ammonia, and chlorine. Appropriate measures to provide
      protection from respiratory effects of chemical incidents could prevent injuries.

PMID- 25856535
TI  - Public health response to acute chemical incidents-Hazardous Substances Emergency
      Events Surveillance, nine states, 1999-2008.
AB  - PROBLEM/CONDITION: Acute chemical incidents (i.e., uncontrolled or illegal
      release or threatened release of hazardous substances lasting <72 hours)
      represent a substantial threat to the environment, public health and safety, and
      community well-being. Providing a timely and appropriate public health response
      can prevent or reduce the impact of these incidents. REPORTING PERIOD: 1999-2008.
      DESCRIPTION OF SYSTEM: The Hazardous Substances Emergency Events Surveillance
      (HSEES) system was operated by the Agency for Toxic Substances and Disease
      Registry (ATSDR) during January 1991-September 2009 to describe the public health
      consequences of chemical releases and to develop activities aimed at reducing the
      harm. This report summarizes types, frequency, and trends in public health
      actions taken in response to hazardous substance incidents in the nine states
      (Colorado, Iowa, Minnesota, New York, North Carolina, Oregon, Texas, Washington,
      and Wisconsin) that participated in HSEES during its last 10 full years of data
      collection (1999-2008). RESULTS: Of the 57,975 HSEES incidents that occurred
      during 1999-2008, a total of 15,203 (26.2%) incidents resulted in at least one
      public health action taken to protect public health. Evacuations were ordered in
      4,281 (7.4%) HSEES incidents, shelter in place was ordered in 509 (0.9%)
      incidents, and access to the affected area was restricted in 10,345 (25.9%)
      incidents. Decontamination occurred in 2,171 (3.7%) incidents; 13,461 persons
      were decontaminated, including 1,152 injured persons. Actions to protect public
      health (e.g., environmental sampling or issuance of health advisories) were taken
      in 6,693 (11.5%) incidents. The highest number of evacuations and orders to
      shelter in place occurred in Washington (n = 558 [16.1%] and n = 121 [3.2%],
      respectively). Carbon monoxide and ammonia releases resulted in the highest
      percentage of orders to evacuate and shelter in place. The most frequently
      reported responders to chemical incidents were company response teams.
      INTERPRETATION: The most frequent public health response was restricting access
      to the area (26% of incidents), public health actions (12%), evacuation (7%),
      decontamination (4%), and shelter-in-place (1%). Ammonia and carbon monoxide were
      associated with adverse health effects in the population and the most public
      health response actions. Therefore, these chemicals can be considered a high
      priority for prevention and response efforts. PUBLIC HEALTH IMPLICATIONS: States
      and communities can collaborate with facilities to use the information collected
      through community right-to-know legislation and this report to improve chemical
      safety and protect public health and the environment, such as being prepared to
      handle the most common chemicals in their area and probable public health
      actions.

PMID- 25856536
TI  - Geographic distribution of acute chemical incidents-Hazardous Substances
      Emergency Events Surveillance, nine states, 1999-2008.
AB  - PROBLEM/CONDITION: Hazardous chemicals are transported and used widely in the
      United States, and acute chemical releases (lasting <72 hours) are not uncommon.
      Characterizing acute incidents within geographic areas can help researchers
      identify spatial patterns and differences and enable public and environmental
      health and safety practitioners, members of local emergency planning committees,
      preparedness coordinators, industry managers, emergency responders, and others to
      prepare for and respond to chemical incidents. REPORTING PERIOD: 1999-2008.
      DESCRIPTION OF SYSTEM: The Hazardous Substances Emergency Events Surveillance
      (HSEES) system was operated by the Agency for Toxic Substances and Disease
      Registry (ATSDR) during January 1991-September 2009 to collect data on hazardous
      chemical releases that would enable researchers to describe the public health
      consequences of these acute releases and to develop activities aimed at reducing
      the ensuing harm to the public. This report summarizes data for the geographic
      distribution of reported acute incidents by states, counties, and Metropolitan
      Statistical Areas (MSAs) from the nine states (Colorado, Iowa, Minnesota, New
      York, North Carolina, Oregon, Texas, Washington, and Wisconsin) that participated
      in HSEES during its last 10 full years of data collection (1999-2008). RESULTS: A
      total of 57,975 acute incidents occurred during 1999-2008; five MSAs accounted
      for 40.1% of all incidents. Texas reported 41% of all incidents reported by the
      nine states during the 10-year study period, and Colorado reported the fewest
      incidents (3.4%). INTERPRETATION: Storage, use, and transport of hazardous
      substances often are associated with unanticipated releases. In general, releases
      occurred more frequently in areas that use or store more hazardous chemicals and
      in urbanized areas compared with rural areas. In rural areas, most incidents were
      related to the transport of hazardous chemicals. The primary economic activities
      in an area had a strong influence on the frequency and type of chemicals released
      in the area. PUBLIC HEALTH IMPLICATIONS: Exposure to hazardous chemicals can have
      immediate and serious health consequences. Harmful releases can occur wherever
      hazardous chemicals are used, stored, or transported. The time and location of
      releases is unpredictable. Taken together, these elements underscore the need for
      preparedness. A culture of safety, prevention, and preparedness can minimize the
      consequences of future incidents.

PMID- 25856537
TI  - Top five chemicals resulting in injuries from acute chemical incidents-Hazardous
      Substances Emergency Events Surveillance, nine states, 1999-2008.
AB  - PROBLEM/CONDITION: The Toxic Substances Control Act Chemical Substance Inventory
      lists >84,000 chemicals used in commerce
      (http://www.epa.gov/oppt/existingchemicals/pubs/tscainventory/basic.html). With
      chemicals having a multitude of uses, persons are potentially at risk daily for
      exposure to chemicals as a result of an acute chemical incident (lasting <72
      hours). Depending on the level of exposure and the type of chemical, exposure can
      result in morbidity and, in some cases, mortality. REPORTING PERIOD: 1999-2008.
      DESCRIPTION OF SYSTEM: The Hazardous Substances Emergency Events Surveillance
      (HSEES) system was operated by the Agency for Toxic Substances and Disease
      Registry during January 1991-September 2009 to collect data that would enable
      researchers to describe the public health consequences of chemical incidents and
      to develop activities aimed at reducing the harm from such incidents. This report
      identifies the top five chemicals that caused injuries in the nine states
      (Colorado, Iowa, Minnesota, New York, North Carolina, Oregon, Texas, Washington,
      and Wisconsin) that participated in HSEES during its last 10 full years of data
      collection (1999-2008). RESULTS: Of the 57,975 incidents that were reported,
      54,989 (95%) involved the release of only one chemical. The top five chemicals
      associated with injury were carbon monoxide (2,364), ammonia (1,153), chlorine
      (763), hydrochloric acid (326), and sulfuric acid (318). Carbon monoxide and
      ammonia by far caused the most injuries, deaths, and evacuations. Chlorine, while
      not in the top 10 chemicals released, was in the top five chemicals associated
      with injury because of its hazardous properties. INTERPRETATION: Multiple
      measures can be taken to prevent injuries associated with the top five chemicals.
      Because many carbon monoxide releases occur in residential settings, use of
      carbon monoxide detectors can prevent injuries. Substituting chemicals with less
      lethal alternatives can result in mitigating injuries associated with ammonia.
      Routine maintenance of equipment and engineering controls can reduce injuries
      associated with chlorine and sulfuric acid, and proper chemical handling training
      can reduce injuries associated with hydrochloric acid. PUBLIC HEALTH
      IMPLICATIONS: Understanding the most frequently reported locations where carbon
      monoxide, ammonia, chlorine, hydrochloric acid, and sulfuric acid are released
      along with the most frequently reported contributing factors can help mitigate
      injuries associated with these releases. Prevention initiatives should focus on
      educating the public and workers about the dangers of these chemicals and about
      proper handling of these chemicals along with routine maintenance of equipment.

PMID- 25856538
TI  - Top five industries resulting in injuries from acute chemical incidents-Hazardous
      Substance Emergency Events Surveillance, nine states, 1999-2008.
AB  - PROBLEM/CONDITION: Because industries using and/or producing chemicals are
      located in close proximity to populated areas, U.S. residents are at risk for
      unintentional chemical exposures. REPORTING PERIOD: 1999-2008. DESCRIPTION OF
      SYSTEM: The Hazardous Substances Emergency Events Surveillance (HSEES) system was
      operated by the Agency for Toxic Substances and Disease Registry during January
      1991-September 2009 to collect data that would enable researchers to describe the
      public health consequences of chemical releases and to develop activities aimed
      at reducing the harm from such releases. This report summarizes data for the top
      five industries resulting in injuries from an acute chemical incident (lasting
      <72 hours) occurring in the nine states (Colorado, Iowa, Minnesota, New York,
      North Carolina, Oregon, Texas, Washington, and Wisconsin) that participated in
      HSEES during its last 10 full years of data collection (1999-2008). RESULTS: Five
      industries (truck transportation, educational services, chemical manufacturing,
      utilities, and food manufacturing) accounted for approximately one third of all
      incidents in which persons were injured as a result of unintentional release of
      chemicals; the same five industries were responsible for approximately one third
      of all persons injured as a result of such releases. INTERPRETATION: Acute
      chemical incidents in these five industries resulted in serious public health
      implications including the need for evacuations, morbidity, and mortality. PUBLIC
      HEALTH IMPLICATIONS: Targeting chemical incident prevention and preparedness
      activities towards these five industries provides an efficient use of resources
      for reducing chemical exposures. A variety of methods can be used to minimize
      chemical releases in industries. One example is the Occupational Safety and
      Health Administration's hierarchy of controls model, which focuses on controlling
      exposures to occupational hazards. The hierarchy includes elimination,
      substitution, engineering controls, administrative controls, and use of personal
      protective equipment.

PMID- 25856539
TI  - The role of neuroticism and conscientiousness on mortality risk in older adults
      after child and spouse bereavement.
AB  - OBJECTIVE: Bereavement effects on mortality risk were investigated in 1150
      randomly selected participants, aged 60-104, in the Swedish National Study of
      Aging and Care. METHOD: Cox proportional hazards models, controlling for age,
      gender, functional ability, the personality traits neuroticism and
      conscientiousness as well as time since the latest loss were used to predict
      mortality risk. RESULTS: Having lost a child, spouse or both child and spouse did
      not predict mortality risk. An indirect link between bereavement and mortality
      was found showing for each year since loss the mortality risk decreased by about
      1%. Neuroticism, but not conscientiousness, was associated with mortality risk,
      with a small-effect size. CONCLUSIONS: The different bereavements did not predict
      mortality risk while an indirect link was found showing that mortality risk
      decreased with time.

PMID- 25856540
TI  - Associations between sleep disturbances and diabetes mellitus among blacks with
      metabolic syndrome: Results from the Metabolic Syndrome Outcome Study (MetSO).
AB  - INTRODUCTION: The association between sleep disturbances and cardiometabolic
      diseases has been understudied in blacks with metabolic syndrome. METHODS: This
      study is a cross-sectional analysis of the Metabolic Syndrome Outcome Study
      (MetSO) trial. We assessed insomnia symptoms, sleep duration, and risk for sleep
      apnea. Multivariate logistic regression models evaluated the association between
      sleep disturbances with diabetes mellitus (DM) and the combined outcomes of DM
      and hypertension as well as DM and dyslipidemia. RESULTS: The sample consisted of
      1,013 participants, mean age of 62 +/- 14 years and 61% female. DM was diagnosed
      in 60% of the sample. Sleep apnea risk was observed in 48% of the sample, while
      10% had insomnia symptoms and 65% reported short sleep duration (< 6 hours).
      Sleep apnea risk, but not insomnia or sleep duration, was associated with DM (OR
      1.66; 95% CI 1.21-2.28), adjusting for age, sex, income, obesity (BMI >= 30
      kg/m(2)), tobacco use, alcohol use, hypertension, dyslipidemia, and depression.
      In fully adjusted models, sleep apnea risk was associated with the combined
      outcome of DM-hypertension (OR 1.95; 95% CI 1.42-2.69), but not with diabetes
      dyslipidemia. CONCLUSION: We observed a strong association between sleep apnea
      risk and diabetes mellitus among blacks with metabolic syndrome.

PMID- 25856541
TI  - Presentation of infection in older patients--a prospective study.
AB  - BACKGROUND: Traditional wisdom suggests that infections in older patients have
      atypical presentation, including blunted febrile response. Data are scarce.
      DESIGN: We analyzed data from a prospectively collected database on presentation
      of infection in 4,308 patients, and compared the presentation of older patients
      (>= 75 years) versus adults (< 75 years). SETTINGS: Single tertiary medical
      center. PARTICIPANTS: Patients admitted with suspected bacterial infection during
      2002-2004 and 2010-2011. MEASUREMENTS: We evaluated clinical presentation on day
      of admission, including vital signs and laboratory parameters. RESULTS: No
      difference in fever values as a presenting sign of infection was found between
      older patients and adults (median fever 38.3 degrees C, interquartile range [IQR]
      37.4-39.0 degrees C; and 38.4 degrees C, IQR 37.3-39.0 degrees C, respectively, P
      = 0.08). Median leukocyte count was significantly higher in older patients
      (median 11.60, IQR 8.30-15.72 in older patients; 10.84, 7.50-15.00 in adults, P <
      0.001). Presentation with septic shock, acute renal failure, and reduced
      consciousness was significantly more common in older patients. These findings
      were also consistent in the subgroups of bacteremic patients and patients with
      microbiologically documented infection. CONCLUSION: Elevated fever and
      leukocytosis were found to be at least equally common in older patients compared
      to younger adults as part of the presentation of infection.

PMID- 25856542
TI  - Plasma cytokine levels and risks of abdominal aortic aneurysms: A population
      based prospective cohort study.
AB  - BACKGROUND: Abdominal aortic aneurysm (AAA) is characterized by inflammatory cell
      accumulation in AAA lesions that produce inflammatory cytokines and advance its
      pathogenesis. Peripheral cytokines may predict the degree or risk of AAA. METHODS
      AND RESULTS: ELISA determined plasma interleukin-6 (IL6), IL10, IL17A, IFN-gamma,
      and C-reactive protein (CRP) from 476 AAA patients and 200 controls. AAA patients
      had lower IL6, IFN-gamma, IL10, IL17A, and higher CRP than controls. IL10
      correlated positively with IFN-gamma, IL17A, or IL6, but not CRP in control or
      AAA populations. IL10 associated negatively with systolic blood pressure, whereas
      CRP associated positively with diastolic blood pressure and body mass index. CRP
      was an independent AAA risk factor and correlated positively with aortic
      diameters before and after adjustments for other risk factors. IFN-gamma, IL17A,
      and CRP correlated positively with cross-sectional AAA area after adjustment.
      IL10 correlated positively with AAA growth rate before and after adjustment. The
      risk of death doubled in AAA patients with CRP levels above the median.
      CONCLUSIONS: Reduced IFN-gamma, IL10, and IL17A in AAA patients, positive
      correlations of IFN-gamma and IL17A with cross-sectional AAA area, IL10 with AAA
      growth rate, and IL10 with IFN-gamma and IL17A suggest combined Th1, Th2, and
      Th17 immune responses in human AAAs.

PMID- 25856543
TI  - Extended High-Frequency Bandwidth Improves Speech Reception in the Presence of
      Spatially Separated Masking Speech.
AB  - OBJECTIVES: The hypothesis that extending the audible frequency bandwidth beyond
      the range currently implemented in most hearing aids can improve speech
      understanding was tested for normal-hearing and hearing-impaired participants
      using target sentences and spatially separated masking speech. DESIGN: The
      Hearing In Speech Test (HIST) speech corpus was re-recorded, and four masking
      talkers were recorded at a sample rate of 44.1 kHz. All talkers were male native
      speakers of American English. For each subject, the reception threshold for
      sentences (RTS) was measured in two spatial configurations. In the asymmetric
      configuration, the target was presented from -45 degrees  azimuth and two
      colocated masking talkers were presented from +45 degrees  azimuth. In the
      diffuse configuration, the target was presented from 0 degrees  azimuth and four
      masking talkers were each presented from a different azimuth: +45 degrees , +135
      degrees , -135 degrees , and -45 degrees . The new speech sentences, masking
      materials, and configurations were presented using low-pass filter cutoff
      frequencies of 4, 6, 8, and 10 kHz. For the normal-hearing participants, stimuli
      were presented in the sound field using loudspeakers. For the hearing-impaired
      participants, the spatial configurations were simulated using earphones, and a
      multiband wide-dynamic-range compressor with a modified CAM2 fitting algorithm
      was used to compensate for each participant's hearing loss. RESULTS: For the
      normal-hearing participants (N = 24, mean age 40 years), the RTS improved
      significantly by 3.0 dB when the bandwidth was increased from 4 to 10 kHz, and a
      significant improvement of 1.3 dB was obtained from extending the bandwidth from
      6 to 10 kHz, in both spatial configurations. Hearing-impaired participants (N =
      25, mean age 71 years) also showed a significant improvement in RTS with extended
      bandwidth, but the effect was smaller than for the normal-hearing participants.
      The mean decrease in RTS when the bandwidth was increased from 4 to 10 kHz was
      1.3 dB for the asymmetric condition and 0.5 dB for the diffuse condition.
      CONCLUSIONS: Extending bandwidth from 4 to 10 kHz can improve the ability of
      normal-hearing and hearing-impaired participants to understand target speech in
      the presence of spatially separated masking speech. Future studies of the
      benefits of extended high-frequency amplification should investigate other
      realistic listening situations, masker types, spatial configurations, and room
      reverberation conditions, to determine added value in overcoming the technical
      challenges associated with implementing a device capable of providing extended
      high-frequency amplification.

PMID- 25856544
TI  - Diagnostic efficacy of magnifying endoscopy with narrow-band imaging for gastric
      neoplasms: a meta-analysis.
AB  - BACKGROUND: Magnifying endoscopy with narrow-band imaging (ME-NBI) is a novel,
      image-enhanced endoscopic technique for differentiating gastrointestinal
      neoplasms and potentially enabling pathological diagnosis. OBJECTIVES: The aim of
      this analysis was to assess the diagnostic performance of ME-NBI for gastric
      neoplasms. METHODS: We performed a systematic search of the PubMed, EMbase, Web
      of Science, and Cochrane Library databases for relevant studies. Meta-DiSc
      (version 1.4) and STATA (version 11.0) software were used for the data analysis.
      Random effects models were used to assess diagnostic efficacy. Heterogeneity was
      tested by the Q statistic and I2 statistic. Meta-regression was used to analyze
      the sources of heterogeneity. RESULTS: A total of 10 studies, with 2151 lesions,
      were included. The pooled characteristics of these studies were as follows:
      sensitivity 0.85 (95% confidence interval [CI]: 0.81-0.89), specificity 0.96 (95%
      confidence interval [CI]: 0.95-0.97), and area under the curve (AUC) 0.9647. In
      the subgroup analysis, which compared the diagnostic efficacy of ME-NBI and white
      light imaging (WLI), the pooled sensitivity and specificity of ME-NBI were 0.87
      (95% CI: 0.80-0.92) and 0.93 (95% CI: 0.90-0.95), respectively, and the area
      under the curve (AUC) was 0.9556. In contrast, the pooled sensitivity and
      specificity of WLI were 0.61 (95% CI: 0.53-0.69) and 0.65 (95% CI: 0.60-0.69),
      respectively, and the area under the curve (AUC) was 0.6772. CONCLUSIONS: ME-NBI
      presents a high diagnostic value for gastric neoplasms and has a high
      specificity.

PMID- 25856545
TI  - Lathyrol diterpenes as modulators of P-glycoprotein dependent multidrug
      resistance: structure-activity relationship studies on Euphorbia factor L3
      derivatives.
AB  - Five series of 37 new acylate and epoxide derivatives (3-39) of Euphorbia factor
      L3, a lathyrol diterpene isolated from Euphorbia lathyris, were designed by
      modifying the hydroxyl moiety of C-3, C-5, or C-15. Chemoreversal effects of the
      acylates on multidrug resistance (MDR) were evaluated in breast cancer multidrug
      resistant MCF-7/ADR cells that overexpress P-glycoprotein (P-gp). Eight
      derivatives exhibited greater chemoreversal ability than verapamil (VRP) against
      adriamycin (ADR) resistance. Compounds 19 and 25 exhibited 4.8 and 4.0 times,
      respectively, more effective reversal ability than VRP against ADR resistance. To
      determine the key characteristics of Euphorbia factor L3 derivatives that
      contribute to MDR reversal, we conducted a structure-activity relationship study
      of these compounds. The simulation studies indicated different possible
      mechanisms and revealed the important influence of hydrophobic interactions and
      hydrogen bonds in the flexible cavity of P-gp. 

PMID- 25856547
TI  - Activation of the gamma-Aminobutyric Acid Type B (GABA(B)) Receptor by Agonists
      and Positive Allosteric Modulators.
AB  - Since the discovery of the GABA(B) agonist and muscle relaxant baclofen, there
      have been substantial advancements in the development of compounds that activate
      the GABA(B) receptor as agonists or positive allosteric modulators. For the
      agonists, most of the existing structure-activity data apply to understanding the
      role of substituents on the backbone of GABA as well as replacing the carboxylic
      acid and amine groups. In the cases of the positive allosteric modulators, the
      allosteric binding site(s) and structure-activity relationships are less well
      defined; however, multiple classes of molecules have been discovered. The recent
      report of the X-ray structure of the GABA(B) receptor with bound agonists and
      antagonists provides new insights for the development of compounds that bind the
      orthosteric site of this receptor. From a therapeutic perspective, these data
      have enabled efforts in drug discovery in areas of addiction-related behavior,
      the treatment of anxiety, and the control of muscle contractility.

PMID- 25856548
TI  - Redox potentials of protein disulfide bonds from free-energy calculations.
AB  - Thiol/disulfide exchange in proteins is a vital process in all organisms. To
      ensure specificity, the involved thermodynamics and kinetics are believed to be
      tailored by the structure and dynamics of the protein hosting the thiol/disulfide
      pair. We here aim at predicting the thermodynamics of thiol/disulfide pairs in
      proteins. We devise a free-energy calculation scheme, which makes use of the
      Crooks Gaussian intersection method to estimate the redox potential of
      thiol/disulfide pairs in 12 proteins belonging to the thioredoxin superfamily,
      namely, thioredoxins, glutaredoxins, and thiol-disulfide oxidoreductases in
      disulfide bond formation systems. We obtained a satisfying correlation of
      computed with experimental redox potentials (varying by 160 mV), with a residual
      error of ~40 mV (8 kJ/mol), which drastically reduces when considering a less
      diverse set of only thioredoxins. Our simple and transferrable approach provides
      a route toward estimating redox potentials of any disulfide-containing protein
      given that its (reduced or oxidized) structure is known and thereby represents a
      step toward a rational design of redox proteins. 

PMID- 25856546
TI  - Factors influencing goal attainment in patients with post-stroke upper limb
      spasticity following treatment with botulinum toxin A in real-life clinical
      practice: sub-analyses from the Upper Limb International Spasticity (ULIS)-II
      Study.
AB  - In this post-hoc analysis of the ULIS-II study, we investigated factors
      influencing person-centred goal setting and achievement following botulinum toxin
      A (BoNT-A) treatment in 456 adults with post-stroke upper limb spasticity (ULS).
      Patients with primary goals categorised as passive function had greater motor
      impairment (p < 0.001), contractures (soft tissue shortening [STS]) (p = 0.006)
      and spasticity (p = 0.02) than those setting other goal types. Patients with
      goals categorised as active function had less motor impairment (0.0001),
      contracture (p < 0.0001), spasticity (p < 0.001) and shorter time since stroke (p
      = 0.001). Patients setting goals for pain were older (p = 0.01) with more
      contractures (p = 0.008). The proportion of patients achieving their primary goal
      was not impacted by timing of first-ever BoNT-A injection (medium-term (<=1 year)
      vs. longer-term (>1 year)) post-stroke (80.0% vs. 79.2%) or presence or absence
      of severe contractures (76.7% vs. 80.6%), although goal types differed. Earlier
      BoNT-A intervention was associated with greater achievement of active function
      goals. Severe contractures impacted negatively on goal achievement except in pain
      and passive function. Goal setting by patients with ULS is influenced by
      impairment severity, age and time since stroke. Our findings resonate with
      clinical experience and may assist patients and clinicians in selecting
      realistic, achievable goals for treatment.

PMID- 25856549
TI  - Investigation on the Gas-phase decomposition of trichlorfon by GC-MS and
      theoretical calculation.
AB  - The gas phase pyrolysis of trichlorfon was investigated by the on-line gas
      chromatography - mass spectrometry (GC-MS) pyrolysis and theoretical
      calculations. Two reaction channels were proposed in the pyrolytic reaction, by
      analyzing the detected pyrolytic products in the total ion chromatography,
      including 2,2,2-trichloroacetaldehyde, dimethyl phosphite, and dichlorvos.
      Theoretical calculations showed that there is an intramolecular hydrogen bond
      between the hydroxyl group and the phosphate O atom in trichlorfon, through which
      the hydroxyl H atom can be easily transferred to phosphate O atom to trigger two
      pyrolytic channels. In path-a, migration of H atom results in direct
      decomposition of trichlorfon to give 2,2,2-trichloroacetaldehyde and dimethyl
      phosphite in one step. In path-b, migration of H atom in trichlorfon is combined
      with formation of the O-P bond to give an intermediate, followed by HCl
      elimination to afford dichlorvos. Path-a is kinetically more favorable than path
      b, which is consistent with the GC-MS results. 

PMID- 25856550
TI  - Pathogens as biological weapons of invasive species.

PMID- 25856551
TI  - Melatonin for pre- and postoperative anxiety in adults.
AB  - BACKGROUND: Anxiety in relation to surgery is a well-known problem. Melatonin
      offers an atoxic alternative to benzodiazepines in ameliorating this condition in
      the pre- and postoperative period. OBJECTIVES: To assess the effect of melatonin
      on pre- and postoperative anxiety in adults when comparing melatonin with placebo
      or when comparing melatonin with benzodiazepines. SEARCH METHODS: The following
      databases were searched on 19 April 2013: CENTRAL, MEDLINE, EMBASE, CINAHL and
      Web of Science. For ongoing trials and protocols we searched clinicaltrials.gov,
      Current Controlled Trials and the World Health Organization (WHO) International
      Clinical Trials Registry Platform. We reran the search in October 2014. We will
      deal with any studies of interest when we update the review. SELECTION CRITERIA:
      Randomized, placebo-controlled or standard treatment-controlled, or both, studies
      that evaluated the effect of preoperatively administered melatonin on
      preoperative or postoperative anxiety. We included adult patients of both genders
      (15 to 90 years of age) undergoing any kind of surgical procedure in which it was
      necessary to use general, regional or topical anaesthesia. DATA COLLECTION AND
      ANALYSIS: Data were extracted independently by two review authors. Data extracted
      included information about study design, country of origin, number of
      participants and demographic details, type of surgery, type of anaesthesia,
      intervention and dosing regimen, preoperative anxiety outcome measures and
      postoperative anxiety outcome measures. MAIN RESULTS: This systematic review
      identified 12 randomized controlled trials (RCTs) including 774 patients that
      assessed melatonin for treating preoperative anxiety, postoperative anxiety or
      both. Four of the 12 studies compared melatonin, placebo and midazolam, whereas
      the remaining eight studies compared melatonin and placebo only.The quality of
      the evidence for our primary outcome (melatonin versus placebo for preoperative
      anxiety) was high. More than half of the included studies had a low risk of
      selection bias and at least 75% of the included studies had a low risk of
      attrition, performance and detection bias. Most of the included studies had an
      unclear risk of reporting bias.Eight out the 10 studies that assessed the effect
      of melatonin on preoperative anxiety using a visual analogue scale (VAS) (ranging
      from 0 to 100 mm, higher scores indicate greater anxiety) showed a reduction
      compared to placebo. The reported estimate of effect (relative effect -13.36, 95%
      confidence interval (CI) -16.13 to -10.58; high quality evidence) was based on a
      meta-analysis of seven studies. Two studies did not show any difference between
      melatonin and placebo. Two studies comparing melatonin with midazolam using a VAS
      found no evidence of a difference in preoperative anxiety between the two groups
      (relative effect -1.18, 95% CI -2.59 to 0.23; low quality evidence).Eight studies
      assessed the effect of melatonin on postoperative anxiety. Four of these studies
      measuring postoperative anxiety 90 minutes postoperatively using a VAS did not
      find any evidence of a difference between melatonin and placebo (relative effect 
      3.71, 95% CI -9.26 to 1.84). Conversely, two studies showed a reduction of
      postoperative anxiety measured six hours after surgery using the State-Trait
      Anxiety Inventory (STAI) when comparing melatonin with placebo (relative effect 
      5.31, 95% CI -8.78 to -1.84; moderate quality evidence). Two studies comparing
      melatonin with midazolam using a VAS did not find any evidence of a difference
      between the two groups in postoperative anxiety (relative effect -2.02, 95% CI 
      5.82 to 1.78). AUTHORS' CONCLUSIONS: When compared to placebo, melatonin given as
      premedication (tablets or sublingually) can reduce preoperative anxiety in adults
      (measured 50 to 100 minutes after administration). Melatonin may be equally as
      effective as standard treatment with midazolam in reducing preoperative anxiety
      in adults (measured 50 to 100 minutes after administration). The effect of
      melatonin on postoperative anxiety (measured 90 minutes and 6 hours after
      surgery) in adults is mixed but suggests an overall attenuation of the effect
      compared to preoperatively.

PMID- 25856552
TI  - Job exposure matrix for electric shock risks with their uncertainties.
AB  - We present an update to an electric shock job exposure matrix (JEM) that assigned
      ordinal electric shocks exposure for 501 occupational titles based on electric
      shocks and electrocutions from two available data sources and expert judgment.
      Using formal expert elicitation and starting with data on electric injury, we
      arrive at a consensus-based JEM. In our new JEM, we quantify exposures by adding
      three new dimensions: (1) the elicited median proportion; (2) the elicited 25th
      percentile; and (3) and the elicited 75th percentile of those experiencing
      occupational electric shocks in a working lifetime. We construct the relative
      interquartile range (rIQR) based on uncertainty interval and the median. Finally,
      we describe overall results, highlight examples demonstrating the impact of cut
      point selection on exposure assignment, and evaluate potential impacts of such
      selection on epidemiologic studies of the electric work environment. In
      conclusion, novel methods allowed for consistent exposure estimates that move
      from qualitative to quantitative measures in this population-based JEM.
      Overlapping ranges of median exposure in various categories reflect our limited
      knowledge about this exposure. 

PMID- 25856553
TI  - Effect of a multi-level education intervention model on knowledge and attitudes
      of accidental injuries in rural children in Zunyi, Southwest China.
AB  - OBJECTIVE: To explore the effect of a school-family-individual (SFI) multi-level
      education intervention model on knowledge and attitudes about accidental injuries
      among school-aged children to improve injury prevention strategies and reduce the
      incidence of pediatric injuries. METHODS: The random sample of rural school-aged
      children were recruited by using a multistage, stratified, cluster sampling
      method in Zunyi, Southwest China from 2012 to 2014, and 2342 children were
      randomly divided into intervention and control groups. Then children answered a
      baseline survey to collect knowledge and attitude scores (KAS) of accidental
      injuries. In the intervention group, children, their parents/guardians and the
      school received a SFI multi-level education intervention, which included a
      children's injury-prevention poster at schools, an open letter about security
      instruction for parents/guardians and multiple-media health education (Microsoft
      PowerPoint lectures, videos, handbooks, etc.) to children. Children in the
      control group were given only handbook education. After 16 months, children
      answered a follow-up survey to collect data on accidental injury types and
      accidental injury-related KAS for comparing the intervention and control groups
      and baseline and follow-up data. RESULTS: The distribution of gender was not
      significantly different while age was different between the baseline and follow
      up survey. At baseline, the mean KAS was lower for the intervention than control
      group (15.37 +/- 3.40 and 18.35 +/- 5.01; p < 0.001). At follow-up, the mean KAS
      was higher for the intervention than control group (21.16 +/- 3.05 and 20.02 +/-
      3.40; p < 0.001). The increase in KAS in the intervention and control groups was
      significant (p < 0.001; KAS: 5.79 vs. 1.67) and suggested that children's injury
      related KAS improved in the intervention group. Moreover, the KAS between the
      groups differed for most subtypes of incidental injuries (based on International
      Classification of Diseases 10, ICD-10) (p < 0.05). Before intervention, 350
      children had reported their accident injury episodes, while after intervention
      237 children had reported their accidental injury episodes in the follow-up
      survey. CONCLUSIONS: SFI multi-level education intervention could significantly
      increase KAS for accidental injuries, which should improve children's prevention
      related knowledge and attitudes about such injuries. It should help children
      change their risk behaviors and reduce the incidence of accidental injuries. Our
      results highlight a new intervention model of injury prevention among school-aged
      children.

PMID- 25856554
TI  - Evaluation of E-cigarette liquid vapor and mainstream cigarette smoke after
      direct exposure of primary human bronchial epithelial cells.
AB  - E-cigarettes are emerging products, often described as "reduced-risk" nicotine
      products or alternatives to combustible cigarettes. Many smokers switch to e
      cigarettes to quit or significantly reduce smoking. However, no regulations for e
      cigarettes are currently into force, so that the quality and safety of e-liquids
      is not necessarily guaranteed. We exposed primary human bronchial epithelial
      cells of two different donors to vapor of e-cigarette liquid with or without
      nicotine, vapor of the carrier substances propylene glycol and glycerol as well
      as to mainstream smoke of K3R4F research cigarettes. The exposure was done in a
      CULTEX(r) RFS compact  module, allowing the exposure of the cells at the air
      liquid interface. 24 h post-exposure, cell viability and oxidative stress levels
      in the cells were analyzed. We found toxicological effects of e-cigarette vapor
      and the pure carrier substances, whereas the nicotine concentration did not have
      an effect on the cell viability. The viability of mainstream smoke cigarette
      exposed cells was 4.5-8 times lower and the oxidative stress levels 4.5-5 times
      higher than those of e-cigarette vapor exposed cells, depending on the donor. Our
      experimental setup delivered reproducible data and thus provides the opportunity
      for routine testing of e-cigarette liquids to ensure safety and quality for the
      user. 

PMID- 25856555
TI  - MiR-506 suppresses tumor proliferation and invasion by targeting FOXQ1 in
      nasopharyngeal carcinoma.
AB  - MiRNAs are small noncoding RNAs that play important roles in various biological
      processes including tumorigenesis. However, little is known about the expression
      and function of miR-506 in nasopharyngeal carcinoma (NPC). In this study, we
      showed that miR-506 was downregulated in nasopharyngeal carcinoma (NPC) cell
      lines and tissues. Ectopic expression of miR-506 dramatically suppressed cell
      proliferation, colony formation and invasion. Moreover, we identified the
      Forkhead box Q1 (FOXQ1) gene as a novel direct target of miR-506. MiR-506 exerts
      its tumor suppressor function through inhibition of the FOXQ1, which was involved
      in tumor metastasis and proliferation in various cancers. Furthermore, the
      expression of FOXQ1 is up-regulated in NPC cell lines and tissues. Taken
      together, our results indicate that miR-506 functions as a tumor suppressor miRNA
      in NPC and that its suppressive effects are mediated chiefly by repressing FOXQ1
      expression. 

PMID- 25856556
TI  - Characterization of the mantle transcriptome of yesso scallop (Patinopecten
      yessoensis): identification of genes potentially involved in biomineralization
      and pigmentation.
AB  - The Yesso scallop Patinopecten yessoensis is an economically important marine
      bivalve species in aquaculture and fishery in Asian countries. However, limited
      genomic resources are available for this scallop, which hampers investigations
      into molecular mechanisms underlying their unique biological characteristics,
      such as shell formation and pigmentation. Mantle is the special tissue of P.
      yessoensis that secretes biomineralization proteins inducing shell deposition as
      well as pigmentation on the shells. However, a current deficiency of
      transcriptome information limits insight into mechanisms of shell formation and
      pigmentation in this species. In this study, the transcriptome of the mantle of
      P. yessoensis was deeply sequenced and characterized using Illumina RNA-seq
      technology. A total of 86,521 unique transcripts are assembled from 55,884,122
      reads that passed quality filters, and annotated, using Gene Ontology
      classification. A total of 259 pathways are identified in the mantle
      transcriptome, including the calcium signaling and melanogenesis pathways. A
      total of 237 unigenes that are homologous to 102 reported biomineralization genes
      are identified, and 121 unigenes that are homologous to 93 known proteins related
      to melanin biosynthesis are found. Twenty-three annotated unigenes, which are
      mainly homologous to calmodulin and related proteins, Ca2+/calmodulin-dependent
      protein kinase, adenylate/guanylate cyclase, and tyrosinase family are
      potentially involved in both biomineralization and melanin biosynthesis. It is
      suggested that these genes are probably not limited in function to induce shell
      deposition by calcium metabolism, but may also be involved in pigmentation of the
      shells of the scallop. This potentially supports the idea that there might be a
      link between calcium metabolism and melanin biosynthesis, which was previously
      found in vertebrates. The findings presented here will notably advance the
      understanding of the sophisticated processes of shell formation as well as shell
      pigmentation in P. yessoensis and other bivalve species, and also provide new
      evidence on gene expression for the understanding of pigmentation and
      biomineralization not only in invertebrates but also probably in vertebrates. 

PMID- 25856557
TI  - Methyl jasmonate, yeast extract and sucrose stimulate phenolic acids accumulation
      in Eryngium planum L. shoot cultures.
AB  - Eryngium planum L. has been reported as a medicinal plant used in traditional
      medicine in Europe. The tissue cultures may be an alternative source of the
      biomass rich in desired bioactive compounds. The purpose of this study was to
      investigate the influence of the biotechnological techniques on the selected
      phenolic acids accumulation in the agitated shoot cultures of E. planum.
      Qualitative and quantitative analyses of those compounds in 50% aqueous -
      methanolic extracts from the biomass were conducted by applying the HPLC method.
      Methyl jasmonate (MeJA), yeast extract (YE) and sucrose (Suc) stimulated
      accumulation of the phenolic acids: rosmarinic (RA), chlorogenic (CGA) and
      caffeic (CA) in in vitro shoot cultures. Cultivation of shoots in liquid MS media
      supplemented with 1.0 mg L(-1) 6-benzyladenine and 0.1 mg L(-1) indole-3-acetic
      acid in the presence of 100 uM MeJA for 48h was an optimum condition of
      elicitation and resulted in approximately 4.5-fold increased content of RA + CGA
      + CA in plant material compared to the control (19.795 mg g(-1) DW, 4.36 mg g(-1)
      DW, respectively). The results provide the first evidence that the selected
      phenolic acids can be synthesized in elicited shoot cultures of flat sea holly in
      higher amount than in untreated shoots. 

PMID- 25856558
TI  - Skin metabolism established with the use of MetaSite for selected retinoids
      employed in topical and systemic treatment of various skin disorders and found in
      cosmeceuticals.
AB  - PURPOSE: Besides being widely used in cosmetics, retinoids are potent therapeutic
      agents used topically and systemically as anti-acne agents. The aim of this study
      was to predict with the use of MetaSite the skin metabolism of selected retinoids
      employed in treatment of skin disorders and found in cosmeceuticals. The
      following compounds were studied: retinol, retinaldehyde, retinoic acid, retinyl
      acetate, retinyl palmitate, acitretin, etretinate, adapalene and bexarotene.
      METHODS: MetaSite, Molecular Discovery Ltd. is a computational model that enables
      prediction of cytochrome P450-dependant metabolism. This software indicates atoms
      in the molecule structure that are mostly vulnerable to metabolic changes and
      predicts the metabolite structures. RESULTS: MetaSite indicated that retinol and
      retinal metabolites were obtained through hydroxylation of the methyl group
      located in the position 3 of the aliphatic chain, whereas retinoic acid
      biotransformation would occur principally in the carbon atom situated in the
      position 4 in the cyclohexene ring. In acitretin molecule, carbon atom of the
      methoxy group attached to the benzene ring displayed the highest probability of
      biotransformation. In etretinate, metabolic reactions would occur principally on
      the carbon atom of the final ethyl group of the molecule. CONCLUSIONS: MetaSite
      metabolism predictions for retinoic acid, acitretin, etretinate, adapalene and
      bexarotene were in agreement with experimental findings. In case of compounds
      being converted by catalysts other than cytochrome P450 enzymes, the primary
      metabolites predicted by MetaSite differ from those reported previously. In
      conclusion, MetaSite is a useful tool that can aid identification of the major
      metabolites of compounds being administered topically.

PMID- 25856559
TI  - Protective effects of quercetin on cadmium fluoride induced oxidative stress at
      different intervals of time in mouse liver.
AB  - Quercetin, a member of the flavonoid family is a major antioxidant acquired in
      humans by food consumption, while Cadmium fluoride (CdF2) is one of the naturally
      occurring chemicals having adverse effects. The protective effect of quercetin on
      time dependent oxidative damage induced in mice liver by CdF2 was studied in the
      following groups of mice consisting of six mice each: (i) control group; (ii)
      mice treated with single i.p injection of 2 mg/kg bw CdF2 for 24 h; (iii) mice
      treated with single i.p injection of 2 mg/kg bw CdF2 for 48 h; (iv) mice treated
      with single i.p injection of quercetin (100 mg/kg bw); (v) mice treated with i.p
      injection of 100 mg/kg bw of quercetin followed by i.p injection of CdF2 (2 mg/kg
      bw) for 24 h; and (vi) mice treated with i.p injection of 100mg/kg bw of
      quercetin followed by CdF2 (2 mg/kg bw) for 48 h. Administration of quercetin two
      hours before CdF2 significantly reduced the biochemical alterations in reduced
      glutathione, ascorbic acid, lipid peroxidation, super oxide dismutase, catalase
      and total protein (p<0.05). Histopathology also showed the protective effect of
      quercetin. The livers treated with CdF2 were atrophic, markedly nodular, inflamed
      and necrotic. However, this effect was reduced to a minimum in the mice pre
      treated for two hours with quercetin. 

PMID- 25856560
TI  - Study of O/W micro- and nano-emulsions based on propylene glycol diester as a
      vehicle for geranic acid.
AB  - Nano- and microemulsions containing as the oil phase caprylic/capric propylene
      glycol diesters (Crodamol PC) were investigated as potential vehicle for
      controlled release of geranic acid. The influence of emulsifiers and co
      surfactants on stability of the emulsions was investigated. Different kind of
      polysorbates (ethoxylated esters of sorbitan and fatty acids) were applied as the
      emulsifiers. The short-chain alcohols (ethanol, 1-propanol, 1-butanol) were used
      as co-surfactants. The emulsions were prepared at ambient temperature (25 degrees
      C), by the phase inversion composition method (PIC). The stable O/W high
      dispersed emulsion systems based on Crodamol PC, of mean droplets size less than
      200 nm, were prepared. Microemulsions stabilized by the mixture of Polisorbat 80
      and 1-butanol were characterized by the largest degree of dispersion (137 nm) and
      the lowest PDI value (0.094), at surfactant/co-surfactant: oil weight ratio
      90:10. The stable nano-emulsion (mean droplet size of 33 nm) was obtained for
      surfactant: oil (S:O) weight ratio 90:10, without co-surfactant addition. This
      nano-emulsion was chosen to release studies. The obtained results showed that the
      prepared stable nano-emulsion can be used as a carrier for controlled release of
      geranic acid. The active substance release from the nano-emulsion and the oil
      solution, after 24 hours was 22%. 

PMID- 25856561
TI  - Methyl jasmonate stimulates biosynthesis of 2-phenylethylamine, phenylacetic acid
      and 2-phenylethanol in seedlings of common buckwheat.
AB  - Methyl jasmonate has a strong effect on secondary metabolizm in plants, by
      stimulating the biosynthesis a number of phenolic compounds and alkaloids. Common
      buckwheat (Fagopyrum esculentum Moench) is an important source of biologically
      active compounds. This research focuses on the detection and quantification of 2
      phenylethylamine and its possible metabolites in the cotyledons, hypocotyl and
      roots of common buckwheat seedlings treated with methyl jasmonate. In cotyledons
      of buckwheat sprouts, only traces of 2-phenylethylamine were found, while in the
      hypocotyl and roots its concentration was about 150 and 1000-times higher,
      respectively. Treatment with methyl jasmonate resulted in a 4-fold increase of
      the 2-phenylethylamine level in the cotyledons of 7-day buckwheat seedlings, and
      an 11-fold and 5-fold increase in hypocotyl and roots, respectively. Methyl
      jasmonate treatment led also to about 4-fold increase of phenylacetic acid
      content in all examined seedling organs, but did not affect the 2-phenylethanol
      level in cotyledons, and slightly enhanced in hypocotyl and roots. It has been
      suggested that 2-phenylethylamine is a substrate for the biosynthesis of
      phenylacetic acid and 2-phenylethanol, as well as cinnamoyl 2-phenethylamide. In
      organs of buckwheat seedling treated with methyl jasmonate, higher amounts of
      aromatic amino acid transaminase mRNA were found. The enzyme can be involved in
      the synthesis of phenylpyruvic acid, but the presence of this compound could not
      be confirmed in any of the examined organs of common buckwheat seedling. 

PMID- 25856562
TI  - Antitumor effects of interleukin-6 (IL-6)/interleukin-6 receptor (IL-6R)
      signaling pathway inhibition in clear cell carcinoma of the ovary.
AB  - Among epithelial ovarian cancers, clear cell carcinoma of the ovary (CCC) has
      unique clinical and molecular characteristics that include chemoresistance
      resulting in poor prognosis. It was shown that CCC recently was characterized by
      specific upregulation of the IL-6/IL-6R-signal transducer and activator of
      transcription 3 (Stat3) signaling pathway. In this study, we aim to clarify
      whether IL-6/IL-6R mediated signaling pathway could have clinical relations with
      CCC and to evaluate inhibitory effects of the pathway on CCC carcinogenesis. A
      total of 84 CCC cases collected from primary surgical specimens were evaluated by
      the immunohistochemical analysis for IL-6R and phosphorylated Stat3 (pStat3), and
      we found that high IL-6R expression correlated with poor patient survival both by
      the univariate and multivariate analyses, suggesting that IL-6/IL-6R signaling
      pathway could be implicated in the progression of CCC. We further investigated
      the effects of IL-6/IL-6R mediated signaling pathway inhibition either by IL-6R
      small interfering RNA (siRNA) approach or humanized anti-human IL-6R antibody
      (tocilizumab) in CCC. Inhibition of endogenous IL-6R including tocilizumab in CCC
      cells did reduce cell invasion ability and restored their response to cytotoxic
      reagent. These data suggest that IL-6/IL-6R signaling pathway could act on CCC
      cells to enhance invasion and chemoresistance and, therefore, targeting IL-6/IL
      6R mediated signaling pathway could be a promising therapeutic strategy for CCC.

PMID- 25856563
TI  - Clinical Drug Development Using Dynamic Biomarkers to Enable Personalized Health
      Care in COPD.
AB  - Despite massive investments in the development of novel treatments for
      heterogeneous diseases such as COPD, the resources spent have only benefited a
      fraction of the population treated. Personalized health care to guide selection
      of a suitable patient population already in the clinical development of new
      compounds could offer a solution. This review discusses past successes and
      failures in drug development and biomarker research in COPD, describes research
      in COPD phenotypes and the required characteristics of a suitable biomarker for
      identifying patients at higher risk of progression, and examines the role of
      extracellular matrix proteins found to be upregulated in COPD. Novel biomarkers
      of connective tissue remodeling that may provide added value for a personalized
      approach by detecting subgroups of patients with active disease suitable for
      pharmacologic intervention are discussed. 

PMID- 25856564
TI  - pH-Responsive Poly(ethylene glycol)/Poly(L-lactide) Supramolecular Micelles Based
      on Host-Guest Interaction.
AB  - pH-responsive supramolecular amphiphilic micelles based on benzimidazole
      terminated poly(ethylene glycol) (PEG-BM) and beta-cyclodextrin-modified poly(L
      lactide) (CD-PLLA) were developed by exploiting the host-guest interaction
      between benzimidazole (BM) and beta-cyclodextrin (beta-CD). The dissociation of
      the supramolecular micelles was triggered in acidic environments. An
      antineoplastic drug, doxorubicin (DOX), was loaded into the supramolecular
      micelles as a model drug. The release of DOX from the supramolecular micelles was
      clearly accelerated as the pH was reduced from 7.4 to 5.5. The DOX-loaded PEG
      BM/CD-PLLA supramolecular micelles displayed an enhanced intracellular drug
      release rate in HepG2 cells compared to the pH-insensitive DOX-loaded PEG-b-PLLA
      counterpart. After intravenous injection into nude mice bearing HepG2 xenografts
      by the tail vein, the DOX-loaded supramolecular micelles exhibited significantly
      higher tumor inhibition efficacy and reduced systemic toxicity compared to free
      DOX. Furthermore, the DOX-loaded supramolecular micelles showed a blood clearance
      rate markedly lower than that of free DOX and comparable to that of the DOX
      loaded PEG-b-PLLA micelles after intravenous injection into rats. Therefore, the
      pH-responsive PEG-BM/CD-PLLA supramolecular micelles hold potential as a smart
      nanocarrier for anticancer drug delivery.

PMID- 25856566
TI  - Theoretical studies on the redox-stimulated isomerization in electrochromic
      osmium sulfoxide complexes.
AB  - Redox-stimulated intramolecular isomerization of the DMSO ligand in
      [Os(bpy)2(DMSO)2](2+) (bpy = 2,2'-bipyridine; DMSO = dimethyl sulfoxide) was
      explored theoretically for better understanding the electrochromic properties of
      osmium sulfoxide complexes. It is found that the HOMO-LUMO gap is decreased
      because the electron transfer amount from DMSO1 ligand to Os center using Os-S1
      linkage is larger than that using Os-O1 linkage, which makes the absorption of
      such electrochromic Os(II) sulfoxide complexes red-shifted. Moreover, it is
      observed that Os-O linkage is preferred by the "hard" Os(III) metal and the
      "soft" Os(I) metal prefers Os-S linkage, compared with Os(II). Intrinsic reaction
      pathway calculation results demonstrate that Os-S1 -> Os-O1 isomerization is
      favored by Os(II) oxidation, while Os-O1 -> Os-S1 isomerization is much easier to
      be triggered by reduction of Os(III) or Os(II). In addition, DMSO2 linkage
      isomerization becomes much harder to proceed attributed to the increased bond
      strength between DMSO2 and Os center upon Os(II)-O1 -> Os(II)-S1 rearrangement,
      which makes only one DMSO ligand isomerized observed experimentally. 

PMID- 25856565
TI  - Personality Assessment in the Diagnostic Manuals: On Mindfulness, Multiple
      Methods, and Test Score Discontinuities.
AB  - Recent controversies have illuminated the strengths and limitations of different
      frameworks for conceptualizing personality pathology (e.g., trait perspectives,
      categorical models), and stimulated debate regarding how best to diagnose
      personality disorders (PDs) in the Diagnostic and Statistical Manual of Mental
      Disorders (5th ed.), and in other diagnostic systems (i.e., the International
      Classification of Diseases, the Psychodynamic Diagnostic Manual). In this article
      I argue that regardless of how PDs are conceptualized and which diagnostic system
      is employed, multimethod assessment must play a central role in PD diagnosis. By
      complementing self-reports with evidence from other domains (e.g., performance
      based tests), a broader range of psychological processes are engaged in the
      patient, and the impact of self-perception and self-presentation biases can be
      better understood. By providing the assessor with evidence drawn from multiple
      modalities, some of which provide converging patterns and some of which yield
      divergent results, a multimethod assessment compels the assessor to engage this
      evidence more deeply. The mindful processing that ensues can help minimize the
      deleterious impact of naturally occurring information processing bias and
      distortion on the part of the clinician (e.g., heuristics, attribution errors),
      bringing greater clarity to the synthesis and integration of assessment data. 

PMID- 25856567
TI  - Racial/Ethnic disparities in patient experience with communication in hospitals:
      real differences or measurement errors?
AB  - BACKGROUND: An important aspect of medical care is clear and effective
      communication, which can be particularly challenging for individuals based on
      race/ethnicity. Quality of communication is measured systematically in the
      Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey,
      and analyzed frequently such as in the National Healthcare Disparities Report.
      Caution is needed to discern differences in communication quality from
      racial/ethnic differences in perceptions about concepts or expectations about
      their fulfillment. OBJECTIVES: To examine assumptions about the degree of
      commonality across racial/ethnic groups in their perceptions and expectations,
      and to investigate the validity of conclusions regarding racial/ethnic
      differences in communication quality. METHODS: We used 2007 HCAHPS data from the
      National CAHPS Benchmarking Database to construct racial/ethnic samples that
      controlled for other patient characteristics (828 per group). Using multiple
      groups confirmatory factor analyses, we tested whether the factor structure and
      model parameters (ie, factor loadings, intercepts) differed across groups.
      RESULTS: We identified support for basic tests of equivalence across 7
      racial/ethnic groups in terms of equivalent factor structure and loadings. Even
      stronger support was found for Communication with Doctors and Nurses. However,
      potentially important nonequivalence was found for Communication about Medicines,
      including instances of statistically significant differences between non-Hispanic
      whites and non-Hispanic blacks, Asians, and Native Hawaiian/other Pacific
      Islanders. CONCLUSIONS: Our results provide strongest support for racial/ethnic
      comparisons on Communication with Nurses and Doctors, and reason to caution
      against comparisons on Communication about Medicines due to significant
      differences in model parameters across groups; that is, a lack of invariance in
      the intercept.

PMID- 25856569
TI  - Patients as partners: a qualitative study of patients' engagement in their health
      care.
AB  - To advocate for patients to be more actively involved with the healthcare
      services they receive, particularly patients living with chronic illness, the
      Faculty of Medicine of the University of Montreal and its affiliated hospitals
      developed the Patients as Partners concept where the patient is considered a full
      fledged partner of the health care delivery team and the patient's experiential
      knowledge is recognized. This study aims to show how patients view their
      engagement with healthcare professionals regarding their direct care. Using
      theoretical sampling, 16 semi-structured interviews were conducted with patients
      with chronic illness who were familiar with the concept of Patients as Partners.
      Data analysis followed a constructivist grounded theory approach. Patients
      describe themselves as proactively engaging in three types of practice,
      regardless of health professionals' openness to their role as partners. The first
      is a process of continuous learning that allows them to acquire experiential
      knowledge about their health, as well as scientific information and technical
      know-how. The second involves their assessment of the healthcare they receive, in
      terms of its quality and how it aligns with their personal preferences. It
      includes their assessment of the quality of their relationship with the health
      professional and of the latter's scientific knowledge and technical know-how. The
      third type, adaptation practices, builds on patients' learning and assessments to
      compensate for and adapt to what has been perceived as optimal or non-optimal
      health or healthcare circumstances. Patients appear to play a more active and
      less docile role in their own direct care than suggested so far in the
      literature, regardless of the degree of reciprocity of the partnership or the
      degree to which the health professional seeks to encourage patient engagement. 

PMID- 25856571
TI  - Convergent QSAR studies on a series of NK3 receptor antagonists for schizophrenia
      treatment.
AB  - The dopamine hypothesis states that decreased dopaminergic neurotransmission
      reduces schizophrenia symptoms. Neurokinin-3 receptor (NK3) antagonists reduce
      dopamine release and have shown positive effects in pre-clinical and clinical
      trials. We employed 2D and 3D-QSAR analysis on a series of 40 non-peptide NK3
      antagonists. Multivariate statistical analysis, PCA and HCA, were performed to
      rational training/test set splitting and PLS regression was employed to construct
      all QSAR models. We constructed one highly predictive CoMFA model (q(2)= 0.810
      and r(2)= 0.929) and acceptable HQSAR and CoMSIA models (HQSAR q(2)= 0.644 and
      r(2)= 0.910; CoMSIA q(2)= 0.691, r(2)= 0.911). The three different techniques
      provided convergent physicochemical results. All models indicate cyclopropane,
      piperidine and di-chloro-phenyl ring attached to cyclopropane ring and also the
      amide group attached to the piperidine ring could play an important role in
      ligand-receptor interactions. These findings may contribute to develop potential
      NK3 receptor antagonists for schizophrenia.

PMID- 25856570
TI  - RAP1 GTPase overexpression is associated with cervical intraepithelial neoplasia.
AB  - RAP1 (RAS proximate 1), a small GTP-binding protein of the RAS superfamily, is a
      putative oncogene that is highly expressed in several malignant cell lines and
      types of cancers, including some types of squamous cell carcinoma. However, the
      participation of RAP1 in cervical carcinogenesis is unknown. We conducted a cross
      sectional study of paraffin-embedded cervical biopsies to determine the
      association of RAP1 with cervical intraepithelial neoplasia (CIN). Standard and
      quantitative immunohistochemistry assessment of RAP1 expression in fixed tissue
      was performed on 183 paraffin-embedded cervical biopsies that were classified as
      normal or non-dysplastic mucosa (NDM) (n = 33); CIN grade 1 (n = 84) and CIN
      grade 2/3 (n = 66). A gradual increase in RAP1 expression in NDM < CIN 1 < CIN
      2/3 (p<0.001) specimens was observed and was in agreement with the
      histopathologic diagnosis. A progressive increase in the RAP1 expression levels
      increased the risk of CIN 1 [odds ratio (OR) = 3.50; 95% confidence interval (CI)
      1.30-10.64] 3.5 fold and the risk of CIN 2/3 (OR = 19.86, 95% CI 6.40-70.79)
      nearly 20 fold when compared to NDM. In addition, stereotype ordinal regression
      analysis showed that this progressive increase in RAP1 expression more strongly
      impacted CIN 2/3 than CIN 1. Our findings suggest that RAP1 may be a useful
      biomarker for the diagnosis of CIN. 

PMID- 25856572
TI  - Creation and application of voxelised dosimetric models, and a comparison with
      the current methodology as used for the International Commission on Radiological
      Protection's Reference Animals and Plants.
AB  - Over the past decade, the International Commission on Radiological Protection
      (ICRP) has developed a comprehensive approach to environmental protection that
      includes the use of Reference Animals and Plants (RAPs) to assess radiological
      impacts on the environment. For the purposes of calculating radiation dose, the
      RAPs are approximated as simple shapes that contain homogeneous distributions of
      radionuclides. As uncertainties in environmental dose effects are larger than
      uncertainties in radiation dose calculation, some have argued against more
      realistic dose calculation methodologies. However, due to the complexity of
      organism morphology, internal structure, and density, dose rates calculated via a
      homogenous model may be too simplistic. The purpose of this study is to examine
      the benefits of a voxelised phantom compared with simple shapes for organism
      modelling. Both methods typically use Monte Carlo methods to calculate absorbed
      dose, but voxelised modelling uses an exact three-dimensional replica of an
      organism with accurate tissue composition and radionuclide source distribution.
      It is a multi-stage procedure that couples imaging modalities and processing
      software with Monte Carlo N-Particle. These features increase dosimetric
      accuracy, and may reduce uncertainty in non-human biota dose-effect studies by
      providing mechanistic answers regarding where and how population-level dose
      effects arise. 

PMID- 25856573
TI  - Application of the Commission's recommendations: the 2013-2017 Committee 4
      programme of work.
AB  - Committee 4 of the International Commission on Radiological Protection (ICRP) is
      responsible for developing principles, recommendations, and guidance on the
      protection of people against radiation exposure, and to consider their practical
      application in all exposure situations. Currently, the Committee's efforts are
      focused on the completion of a series of future ICRP publications on the
      implementation of its 2007 Recommendations to the various existing exposure
      situations. A report on protection against radon exposure was published recently
      (ICRP Publication 126), and two documents on protection against cosmic radiation
      in aviation, and naturally occurring radioactive material are under development.
      The programme of work for the forthcoming 2013-2017 period comprises the update
      of ICRP Publication 109 on protection of people in emergency exposure situations,
      and the update of ICRP Publication 111 on protection of people living in long
      term contaminated areas after a nuclear accident, as well as the development of a
      future ICRP publication on the ethics of radiological protection. It also
      includes the preparation of task groups on the application of the Commission's
      recommendations for contaminated sites from past activities and for surface and
      near-surface disposal of radioactive waste. Another important task for Committee
      4 will be to develop a reflection on the tolerability of risk from radiation. 

PMID- 25856574
TI  - ICRP's Second International Symposium.

PMID- 25856575
TI  - Molecular typing and epidemiology profiles of human adenovirus infection among
      paediatric patients with severe acute respiratory infection in China.
AB  - BACKGROUND: Human adenoviruses (HAdVs) have been recognised as pathogens that
      cause a broad spectrum of diseases. The studies on HAdV infection among children
      with severe acute respiratory infection (SARI) are limited. OBJECTIVE: To
      investigate the prevalence, epidemiology, and genotype of HAdV among children
      with SARI in China. STUDY DESIGN: Nasopharyngeal aspirates (NPAs) or induced
      sputum (IS) was collected from hospitalised children with SARIs in Beijing
      (representing Northern China; n = 259) and Zhejiang Province (representing
      Eastern China; n = 293) from 2007 to 2010. The prevalence of HAdV was screened by
      polymerase chain reaction (PCR), followed by sequence typing of PCR fragments
      that targeted the second half of the hexon gene. In addition, co-infection with
      other human respiratory viruses, related epidemiological profiles and clinical
      presentations were investigated. RESULTS AND CONCLUSIONS: In total, 76 (13.8%) of
      552 SARI patients were positive for HAdV, and the infection rates of HAdV in
      Northern and Eastern China were 20.1% (n = 52) and 8.2% (n = 24), respectively.
      HAdV co-infection with other respiratory viruses was frequent (infection rates:
      Northern China, 90.4%; Eastern China, 70.8%). The peak seasons for HAdV-B
      infection was winter and spring. Additionally, members of multiple species (Human
      mastadenovirus B, C, D and E) were circulating among paediatric patients with
      SARI, of which HAdV-B (34/52; 65.4%) and HAdV-C (20/24, 83.3%) were the most
      predominant in Northern and Eastern China, respectively. These findings provide a
      benchmark for future epidemiology and prevention strategies for HAdV.

PMID- 25856576
TI  - Identification and functional analysis of genome mutations in a fluoride
      resistant Streptococcus mutans strain.
AB  - It is known that fluoride-resistant microorganisms are different from fluoride
      sensitive ones in growth, adherence and metabolic activity. It was hypothesized
      that these phenotypic differences were due to stable genotypic changes in the
      fluoride-resistant strains. However, until now, no studies have reported these
      genotypic changes. The aim of this study is to identify such changes in a
      fluoride-resistant Streptococcus mutans strain (C180-2FR) using whole-genome
      shotgun (WGS) sequencing and to examine the potential function of the identified
      mutations by comparing gene expression between the fluoride-sensitive (C180-2)
      and C180-2FR strains. We performed 50 bp paired-end Illumina shotgun sequencing
      for both strains. Through extensive bioinformatic analysis, we were able to
      identify 8 single nucleotide polymorphisms (SNPs) in the genome of C180-2FR,
      which were further confirmed by Sanger sequencing. Expression of the genes
      containing or in proximity to the SNPs in C180-2 and C180-2FR was then quantified
      by real-time PCR. A gene cluster containing genes coding for fluoride antiporters
      was up-regulated 10-fold in C180-2FR when compared to that in C180-2, independent
      of growth phase. Two SNPs are located in this gene cluster, one in its promoter
      region and the other in its protein-coding region. In addition, one gene, which
      codes for a putative glycerol uptake facilitator protein, was found to be down
      regulated by 60% in C180-2FR at an early growth phase. The promoter region of
      this gene contained a SNP. No difference in expression was found for the other
      SNP-containing genes. In summary, using WGS sequencing, we were able to uncover
      genetic changes in the genome of a fluoride-resistant strain. These findings can
      provide new insights into the mechanism of microbial fluoride resistance. 

PMID- 25856577
TI  - Gene editing by co-transformation of TALEN and chimeric RNA/DNA oligonucleotides
      on the rice OsEPSPS gene and the inheritance of mutations.
AB  - Although several site-specific nucleases (SSNs), such as zinc-finger nucleases
      (ZFNs), transcription activator-like effector nucleases (TALENs), and the
      clustered regularly interspaced short palindromic repeat (CRISPR)/Cas, have
      emerged as powerful tools for targeted gene editing in many organisms, to date,
      gene targeting (GT) in plants remains a formidable challenge. In the present
      study, we attempted to substitute a single base in situ on the rice OsEPSPS gene
      by co-transformation of TALEN with chimeric RNA/DNA oligonucleotides (COs),
      including different strand composition such as RNA/DNA (C1) or DNA/RNA (C2) but
      contained the same target base to be substituted. In contrast to zero GT event
      obtained by the co-transformation of TALEN with homologous recombination plasmid
      (HRP), we obtained one mutant showing target base substitution although
      accompanied by undesired deletion of 12 bases downstream the target site from the
      co-transformation of TALEN and C1. In addition to this typical event, we also
      obtained 16 mutants with different length of base deletions around the target
      site among 105 calli lines derived from transformation of TALEN alone (4/19) as
      well as co-transformation of TELAN with either HRP (5/30) or C1 (2/25) or C2
      (5/31). Further analysis demonstrated that the homozygous gene-edited mutants
      without foreign gene insertion could be obtained in one generation. The induced
      mutations in transgenic generation were also capable to pass to the next
      generation stably. However, the genotypes of mutants did not segregate normally
      in T1 population, probably due to lethal mutations. Phenotypic assessments in T1
      generation showed that the heterozygous plants with either one or three bases
      deletion on target sequence, called d1 and d3, were more sensitive to glyphosate
      and the heterozygous d1 plants had significantly lower seed-setting rate than
      wild-type. 

PMID- 25856579
TI  - Concise total synthesis of (+/-)-aspidospermidine.
AB  - (+/-)-Aspidospermidine (1) has been synthesized from the commercially available
      2,3-dihydro-1H-carbazol-4(9H)-one 6 in 10 steps with 20% overall yield. The key
      step of the strategy is a one-pot carbonyl reduction/iminium
      formation/intramolecular conjugate addition reaction that may be applied for the
      synthesis of other Aspidosperma alkaloids.

PMID- 25856578
TI  - From health advice to taboo: community perspectives on the treatment of sleeping
      sickness in the Democratic Republic of Congo, a qualitative study.
AB  - BACKGROUND: Socio-cultural and economic factors constitute real barriers for
      uptake of screening and treatment of Human African Trypanosomiasis (HAT) in the
      Democratic Republic of Congo (DRC). Better understanding and addressing these
      barriers may enhance the effectiveness of HAT control. METHODS: We performed a
      qualitative study consisting of semi-structured interviews and focus group
      discussions in the Bandundu and Kasai Oriental provinces, two provinces lagging
      behind in the HAT elimination effort. Our study population included current and
      former HAT patients, as well as healthcare providers and program managers of the
      national HAT control program. All interviews and discussions were voice recorded
      on a digital device and data were analysed with the ATLAS.ti software. FINDINGS:
      Health workers and community members quoted a number of prohibitions that have to
      be respected for six months after HAT treatment: no work, no sexual intercourse,
      no hot food, not walking in the sun. Violating these restrictions is believed to
      cause serious, and sometimes deadly, complications. These strong prohibitions are
      well-known by the community and lead some people to avoid HAT screening
      campaigns, for fear of having to observe such taboos in case of diagnosis.
      DISCUSSION: The restrictions originally aimed to mitigate the severe adverse
      effects of the melarsoprol regimen, but are not evidence-based and became
      obsolete with the new safer drugs. Correct health information regarding HAT
      treatment is essential. Health providers should address the perspective of the
      community in a constant dialogue to keep abreast of unintended transformations of
      meaning.

PMID- 25856580
TI  - The virtual cell animation collection: tools for teaching molecular and cellular
      biology.
AB  - A cell is a minifactory in which structures and molecules are assembled,
      rearranged, disassembled, packaged, sorted, and transported. Because cellular
      structures and molecules are invisible to the human eye, students often have
      difficulty conceptualizing the dynamic nature of cells that function at multiple
      scales across time and space. To represent these dynamic cellular processes, the
      Virtual Cell Productions team at North Dakota State University develops freely
      available multimedia materials to support molecular and cellular biology learning
      inside and outside the high school and university classroom. 

PMID- 25856581
TI  - Local bladder cancer clusters in southeastern Michigan accounting for risk
      factors, covariates and residential mobility.
AB  - BACKGROUND: In case control studies disease risk not explained by the significant
      risk factors is the unexplained risk. Considering unexplained risk for specific
      populations, places and times can reveal the signature of unidentified risk
      factors and risk factors not fully accounted for in the case-control study. This
      potentially can lead to new hypotheses regarding disease causation. METHODS:
      Global, local and focused Q-statistics are applied to data from a population
      based case-control study of 11 southeast Michigan counties. Analyses were
      conducted using both year- and age-based measures of time. The analyses were
      adjusted for arsenic exposure, education, smoking, family history of bladder
      cancer, occupational exposure to bladder cancer carcinogens, age, gender, and
      race. RESULTS: Significant global clustering of cases was not found. Such a
      finding would indicate large-scale clustering of cases relative to controls
      through time. However, highly significant local clusters were found in Ingham
      County near Lansing, in Oakland County, and in the City of Jackson, Michigan. The
      Jackson City cluster was observed in working-ages and is thus consistent with
      occupational causes. The Ingham County cluster persists over time, suggesting a
      broad-based geographically defined exposure. Focused clusters were found for 20
      industrial sites engaged in manufacturing activities associated with known or
      suspected bladder cancer carcinogens. Set-based tests that adjusted for multiple
      testing were not significant, although local clusters persisted through time and
      temporal trends in probability of local tests were observed. CONCLUSION: Q
      analyses provide a powerful tool for unpacking unexplained disease risk from case
      control studies. This is particularly useful when the effect of risk factors
      varies spatially, through time, or through both space and time. For bladder
      cancer in Michigan, the next step is to investigate causal hypotheses that may
      explain the excess bladder cancer risk localized to areas of Oakland and Ingham
      counties, and to the City of Jackson.

PMID- 25856583
TI  - The German Radiological Society and the Protagonists of Radiology during the Time
      of National Socialism--State of Research, Explanation Attempts, Desiderata and
      Research Prospects.
AB  - The intention of the authors is the recognition and critical analysis of efforts
      to study the history of the German Radiological Society during the time of
      National Socialism from 1933 to 1945 with the goal of determining existing
      desiderata and identifying the resulting research prospects. There is a need to
      study concrete individual biographies of radiologists (members of the German
      Radiological Society, perpetrators, and victims) and their careers before and
      after 1945 as well as the importance of the interdisciplinarity of the discipline
      and the lack of institutional involvement during the "Third Reich". Moreover, the
      comparatively difficult starting situation of the study of the history of the
      German Radiological Society is discussed.

PMID- 25856582
TI  - Frequent down regulation of the tumor suppressor gene a20 in multiple myeloma.
AB  - Multiple myeloma (MM) is a malignant clonal expansion of plasma cells in the bone
      marrow and belongs to the mature B-cell neoplams. The pathogenesis of MM is
      associated with constitutive NF-kappaB activation. However, genetic alterations
      causing constitutive NF-kappaB activation are still incompletely understood.
      Since A20 (TNFAIP3) is a suppressor of the NF-kappaB pathway and is frequently
      inactivated in various lymphoid malignancies, we investigated the genetic and
      epigenetic properties of A20 in MM. In total, of 46 patient specimens analyzed, 3
      single base pair exchanges, 2 synonymous mutations and one missense mutation were
      detected by direct sequencing. Gene copy number analysis revealed a reduced A20
      gene copy number in 8 of 45 (17.7%) patients. Furthermore, immunohistochemical
      staining confirmed that A20 expression correlates with the reduction of A20 gene
      copy number. These data suggest that A20 contributes to tumor formation in a
      significant fraction of myeloma patients. 

PMID- 25856585
TI  - Highlights in B-cell malignancies from the 2013 American Society of Hematology
      annual meeting and exposition.

PMID- 25856584
TI  - Open-close: an alternative strategy to alpha-functionalization of lactone via
      enamine catalysis in one pot under mild conditions.
AB  - An open-close strategy in asymmetric catalysis is newly developed. With this
      powerful strategy, lactols are directly applied as potential precursors of
      lactones in enamine-based asymmetric Michael reactions providing a facile access
      to alpha-functionalized lactones containing two adjacent stereogenic centers as a
      single diastereomer in good to excellent yields (up to 99%) and with excellent
      enantioselectivities (most cases >99%). Moreover, the reaction products are shown
      to give highly functionalized derivatives by stepwise systematic transformations.

PMID- 25856586
TI  - Highlights in B-cell malignancies from the 2013 American Society of Hematology
      annual meeting and exposition: commentary.

PMID- 25856587
TI  - A patient-centered symptom monitoring and reporting system for children and young
      adults with cancer (SyMon-SAYS).
AB  - BACKGROUND: This study evaluated the feasibility of implementing a patient
      centered, technology-based symptom monitoring and reporting system (SyMon-SAYS)
      in pediatric oncology clinics using fatigue as a prototypic symptom. Timely
      identification of symptoms related to multi-modal therapy for children with
      cancer is fundamental to the overall success of cancer treatment. SyMon-SAYS was
      developed to address this need. PROCEDURE: Patients with a cancer diagnosis, ages
      7-21 years, currently on treatment, or off treatment within 6 months, were
      eligible. Patients/parents completed weekly fatigue assessments over 8 weeks via
      the internet or interactive voice response (IVR) by phone. Alert emails were
      generated when pre-defined fatigue score thresholds were met, and fatigue reports
      were forwarded to clinicians accordingly. Clinicians and parents/patients
      received cumulative graphic reports of fatigue scores prior to clinic visits at 4
      and 8 weeks post-baseline to facilitate discussion. Parents/patients completed an
      exit survey at their last visit. RESULTS: Fifty-seven patients/parents completed
      the study. The majority of patients (93%) and parents (78%) felt it was
      very/extremely easy to complete SyMon-SAYS; 95% of parents were satisfied with
      the system; 60% reported it helped deal with their child's fatigue; 70% reported
      that clinicians didn't discuss fatigue with them; 81% would be willing to use
      SyMon-SAYS to manage fatigue and other symptoms. Clinicians reported insufficient
      time to review reports, yet 71% were willing to receive the report on a monthly
      basis. CONCLUSION: SyMon-SAYS is feasible and acceptable to patients and parents.
      Future efforts should focus on better integrating the system into the clinical
      workflow to improve clinicians' acceptance.

PMID- 25856588
TI  - Acoustic property reconstruction of a neonate Yangtze finless porpoise's
      (Neophocaena asiaeorientalis) head based on CT imaging.
AB  - The reconstruction of the acoustic properties of a neonate finless porpoise's
      head was performed using X-ray computed tomography (CT). The head of the deceased
      neonate porpoise was also segmented across the body axis and cut into slices. The
      averaged sound velocity and density were measured, and the Hounsfield units (HU)
      of the corresponding slices were obtained from computed tomography scanning. A
      regression analysis was employed to show the linear relationships between the
      Hounsfield unit and both sound velocity and density of samples. Furthermore, the
      CT imaging data were used to compare the HU value, sound velocity, density and
      acoustic characteristic impedance of the main tissues in the porpoise's head. The
      results showed that the linear relationships between HU and both sound velocity
      and density were qualitatively consistent with previous studies on Indo-pacific
      humpback dolphins and Cuvier's beaked whales. However, there was no significant
      increase of the sound velocity and acoustic impedance from the inner core to the
      outer layer in this neonate finless porpoise's melon. 

PMID- 25856590
TI  - Ideology and microbiology: Ebola, science, and deliberative democracy.

PMID- 25856589
TI  - A temporal gate for viral enhancers to co-opt Toll-like-receptor transcriptional
      activation pathways upon acute infection.
AB  - Viral engagement with macrophages activates Toll-Like-Receptors (TLRs) and
      viruses must contend with the ensuing inflammatory responses to successfully
      complete their replication cycle. To date, known counter-strategies involve the
      use of viral-encoded proteins that often employ mimicry mechanisms to block or
      redirect the host response to benefit the virus. Whether viral regulatory DNA
      sequences provide an opportunistic strategy by which viral enhancer elements
      functionally mimic innate immune enhancers is unknown. Here we find that host
      innate immune genes and the prototypical viral enhancer of cytomegalovirus (CMV)
      have comparable expression kinetics, and positively respond to common TLR
      agonists. In macrophages but not fibroblasts we show that activation of NFkappaB
      at immediate-early times of infection is independent of virion-associated
      protein, M45. We find upon virus infection or transfection of viral genomic DNA
      the TLR-agonist treatment results in significant enhancement of the virus
      transcription-replication cycle. In macrophage time-course infection experiments
      we demonstrate that TLR-agonist stimulation of the viral enhancer and replication
      cycle is strictly delimited by a temporal gate with a determined half-maximal
      time for enhancer-activation of 6 h; after which TLR-activation blocks the viral
      transcription-replication cycle. By performing a systematic siRNA screen of 149
      innate immune regulatory factors we identify not only anticipated anti-viral and
      pro-viral contributions but also new factors involved in the CMV transcription
      replication cycle. We identify a central convergent NFkappaB-SP1-RXR-IRF axis
      downstream of TLR-signalling. Activation of the RXR component potentiated direct
      and indirect TLR-induced activation of CMV transcription-replication cycle;
      whereas chromatin binding experiments using wild-type and enhancer-deletion virus
      revealed IRF3 and 5 as new pro-viral host transcription factor interactions with
      the CMV enhancer in macrophages. In a series of pharmacologic, siRNA and genetic
      loss-of-function experiments we determined that signalling mediated by the TLR
      adaptor protein MyD88 plays a vital role for governing the inflammatory
      activation of the CMV enhancer in macrophages. Downstream TLR-regulated
      transcription factor binding motif disruption for NFkappaB, AP1 and CREB/ATF in
      the CMV enhancer demonstrated the requirement of these inflammatory signal
      regulated elements in driving viral gene expression and growth in cells as well
      as in primary infection of neonatal mice. Thus, this study shows that the
      prototypical CMV enhancer, in a restricted time-gated manner, co-opts through DNA
      regulatory mimicry elements, innate-immune transcription factors to drive viral
      expression and replication in the face of on-going pro-inflammatory antiviral
      responses in vitro and in vivo and; suggests an unexpected role for inflammation
      in promoting acute infection and has important future implications for regulating
      latency. 

PMID- 25856591
TI  - Selecting the right tool for the job.
AB  - There are competing ethical concerns when it comes to designing any clinical
      research study. Clinical trials of possible treatments for Ebola virus are no
      exception. If anything, the competing ethical concerns are exacerbated in trying
      to find answers to a deadly, rapidly spreading, infectious disease. The primary
      goal of current research is to identify experimental therapies that can cure
      Ebola or cure it with reasonable probability in infected individuals. Pursuit of
      that goal must be methodologically sound, practical and consistent with
      prevailing norms governing human subjects research. Some maintain that only
      randomized controlled trials (RCTs) with a placebo or standard-of-care arm can
      meet these conditions. We maintain that there are alternative trial designs that
      can do so as well and that sometimes these are preferable to RCTs. 

PMID- 25856592
TI  - Examining the ethics of clinical use of unproven interventions outside of
      clinical trials during the Ebola epidemic.
AB  - The recent Ebola outbreak in West Africa began in the spring of 2014 and has
      since caused the deaths of over 6,000 people. Since there are no approved
      treatments or prevention modalities specifically targeted at Ebola Virus Disease
      (EVD), debate has focused on whether unproven interventions should be offered to
      Ebola patients outside of clinical trials. Those engaged in the debate have
      responded rapidly to a complex and evolving crisis, however, and this debate has
      not provided much opportunity for in-depth analysis. Additionally, the existing
      literature on access to unproven therapies has focused on contexts like HIV/AIDS
      and oncology, which are very different than the Ebola epidemic. In this paper, we
      examine the ethical issues surrounding access to unproven therapies in the
      context of the recent Ebola outbreak to yield new insights about this
      controversial and unsettled issue. We argue first that, in this context, the
      interests of patients in obtaining access to unproven therapies are not fully
      aligned with the interests of their providers and drug developers. Second, we
      focus on the resource constraints facing providers, funders, and patients and
      conclude that they often counsel against the use of unproven interventions
      against EVD. 

PMID- 25856593
TI  - Kaci Hickox: public health and the politics of fear.
AB  - Kaci Hickox was a nurse who worked with persons who were infected with Ebola in
      West Africa. When she returned to the United States, the governors of New Jersey
      and Maine intervened to confine her to inpatient quarantine despite the fact that
      she was asymptomatic and had no serological evidence of infection. She defied the
      quarantine which resulted in enormous public attention and discussion of
      quarantine and public fear. This article summarizes the case discussing the
      history of the case, the government actions, and the final legal rulings. 

PMID- 25856594
TI  - Ebola, team communication, and shame: but shame on whom?
AB  - Examined as an isolated situation, and through the lens of a rare and feared
      disease, Mr. Duncan's case seems ripe for second-guessing the physicians and
      nurses who cared for him. But viewed from the perspective of what we know about
      errors and team communication, his case is all too common. Nearly 440,000 patient
      deaths in the U.S. each year may be attributable to medical errors. Breakdowns in
      communication among health care teams contribute in the majority of these errors.
      The culture of health care does not seem to foster functional, effective
      communication between and among professionals. Why? And more importantly, why do
      we not do something about it? 

PMID- 25856595
TI  - Caring for the suffering: meeting the Ebola crisis responsibly.
AB  - The current Ebola virus epidemic in Western Africa appears to be spiraling out of
      control. The worst-case projections suggested that the unchecked spread could
      result in almost 1.4 million cases by the end of January 2015 with a case
      fatality rate of at least 50%. The United States and European nations have begun
      to respond in earnest with promises of supplies, isolation beds, and trained
      health care personnel in an effort to contain the epidemic and care for the sick.
      However, there is neither a vaccine nor specific treatment for Ebola infection,
      and therapy is ideally centered on supportive care. I have previously argued that
      the provision of palliative care is obligatory during an overwhelming health
      catastrophe, notably pandemic influenza. Since affected Ebola patients have best
      outcomes with technologically advanced intensive care--resources in scarce supply
      in the area--I suggest that the only acceptable approach to large numbers of very
      sick, dying, and suffering Ebola patients who overwhelm the resources available
      to successfully manage them is effective palliative care. However, this could
      hasten death in this vulnerable population and hence, while ethically and
      medically justifiable, is not without social risk.

PMID- 25856596
TI  - Right job, wrong tool: a commentary on designing clinical trials for Ebola virus
      disease.

PMID- 25856597
TI  - Controlling Ebola trials.

PMID- 25856598
TI  - Thoughts on alternative designs for clinical trials for Ebola treatment research.

PMID- 25856599
TI  - Expand the toolkit!

PMID- 25856600
TI  - Impure politics and pure science: efficacious Ebola medications are only a
      palliation and not a cure for structural disadvantage.

PMID- 25856601
TI  - Not all RCTs are created equal: lessons from early AIDS trials.

PMID- 25856602
TI  - The goals of research during an epidemic.

PMID- 25856603
TI  - Placing and evaluating unproven interventions within a clinical ethical taxonomy
      of treatments for Ebola virus disease.

PMID- 25856604
TI  - In particular circumstances attempting unproven interventions is permissible and
      even obligatory.

PMID- 25856605
TI  - Infection control measures and debts of gratitude.

PMID- 25856606
TI  - Health communication, public mistrust, and the politics of "rationality".

PMID- 25856607
TI  - Working side by side, but not talking enough: accident causation in the emergency
      department care of Thomas Eric Duncan.

PMID- 25856608
TI  - Communication and communicable disease control: lessons from Ebola virus disease.

PMID- 25856609
TI  - Heightened vulnerability, reduced oversight, and ethical breaches on the Internet
      in the West African Ebola epidemic.

PMID- 25856610
TI  - Everyday ethics and Ebola: planning for the unlikely.

PMID- 25856612
TI  - Accountability and public health policies impacting proper Ebola response: time
      for a bioethics oversight board.

PMID- 25856611
TI  - Weighing the importance of palliation of symptoms for Ebola patients during the
      epidemic in West Africa.

PMID- 25856613
TI  - Challenging cases in research ethics.

PMID- 25856614
TI  - Navigating parental permission for neonatal research.

PMID- 25856615
TI  - Informed consent and parental permission for research: rules, roles, and
      relationships.

PMID- 25856616
TI  - Research involving premature infants: timing is everything.

PMID- 25856617
TI  - Precluding consent by clinicians who are both the attending and the investigator:
      an outdated shibboleth?

PMID- 25856618
TI  - Protecting research subject welfare in preventive trials for autosomal dominant
      Alzheimer's disease.

PMID- 25856619
TI  - When there are only two who can tango: ethical concerns at the juncture of highly
      novel interventions and precisely targeted research populations.

PMID- 25856620
TI  - Conceptualization and assessment of vulnerability in a complex international
      Alzheimer's research study.

PMID- 25856621
TI  - Barriers and facilitators to the consent process in a study of complex genetic
      factors.

PMID- 25856623
TI  - Response to open peer commentaries on "Caring for the suffering: meeting the
      Ebola crisis responsibly".

PMID- 25856624
TI  - The perfect must not overwhelm the good: response to open peer commentaries on
      "Selecting the right tool for the job".

PMID- 25856625
TI  - Pyriform sinus soft-tissue mass recurring in esophagus after excision.

PMID- 25856626
TI  - Development of n-Type Semiconductor Based on Cyclopentene- or Cyclohexene-Fused
      [C60]-Fullerene Derivatives.
AB  - Properties of cyclopentene- or cyclohexene-fused [C60]-fullerene derivatives as
      the acceptor in photovoltaic cells have been investigated by use of poly(3
      hexylthiophene) (P3HT) as the model donor polymer. Several cyclopentene- or
      cyclohexene-fused [C60]-fullerene derivatives show high power conversion
      efficiency (PCE). The highest PCE was obtained for 3',6'-dihydro-4'
      phenoxycarbonyl-6'-methylbenzo[1,9][5,6](C60-Ih)fullerene (3.2%); this is
      superior to that of [C60]-PCBM with the P3HT polymer under the same experimental
      conditions. PCE of the OPV devices with alkyl-substituted cyclohexene-fused [C60]
      fullerenes depended on the alkyl substituent on the cyclohexene ring; compounds
      with substituents of odd-number alkyl groups showed better PCE than those
      compounds possessing even-number alkyl groups. 

PMID- 25856627
TI  - Magnetic cell labeling of primary and stem cell-derived pig hepatocytes for MRI
      based cell tracking of hepatocyte transplantation.
AB  - Pig hepatocytes are an important investigational tool for optimizing hepatocyte
      transplantation schemes in both allogeneic and xenogeneic transplant scenarios.
      MRI can be used to serially monitor the transplanted cells, but only if the
      hepatocytes can be labeled with a magnetic particle. In this work, we describe
      culture conditions for magnetic cell labeling of cells from two different pig
      hepatocyte cell sources; primary pig hepatocytes (ppHEP) and stem cell-derived
      hepatocytes (PICM-19FF). The magnetic particle is a micron-sized iron oxide
      particle (MPIO) that has been extensively studied for magnetic cell labeling for
      MRI-based cell tracking. ppHEP could endocytose MPIO with labeling percentages as
      high as 70%, achieving iron content as high as ~55 pg/cell, with >75% viability.
      PICM-19FF had labeling >97%, achieving iron content ~38 pg/cell, with viability
      >99%. Extensive morphological and functional assays indicated that magnetic cell
      labeling was benign to the cells. The results encourage the use of MRI-based cell
      tracking for the development and clinical use of hepatocyte transplantation
      methodologies. Further, these results generally highlight the importance of
      functional cell assays in the evaluation of contrast agent biocompatibility. 

PMID- 25856628
TI  - Respiratory syncytial virus fusion protein promotes TLR-4-dependent neutrophil
      extracellular trap formation by human neutrophils.
AB  - Acute viral bronchiolitis by Respiratory Syncytial Virus (RSV) is the most common
      respiratory illness in children in the first year of life. RSV bronchiolitis
      generates large numbers of hospitalizations and an important burden to health
      systems. Neutrophils and their products are present in the airways of RSV
      infected patients who developed increased lung disease. Neutrophil Extracellular
      Traps (NETs) are formed by the release of granular and nuclear contents of
      neutrophils in the extracellular space in response to different stimuli and
      recent studies have proposed a role for NETs in viral infections. In this study,
      we show that RSV particles and RSV Fusion protein were both capable of inducing
      NET formation by human neutrophils. Moreover, we analyzed the mechanisms involved
      in RSV Fusion protein-induced NET formation. RSV F protein was able to induce NET
      release in a concentration-dependent fashion with both neutrophil elastase and
      myeloperoxidase expressed on DNA fibers and F protein-induced NETs was dismantled
      by DNase treatment, confirming that their backbone is chromatin. This viral
      protein caused the release of extracellular DNA dependent on TLR-4 activation,
      NADPH Oxidase-derived ROS production and ERK and p38 MAPK phosphorylation.
      Together, these results demonstrate a coordinated signaling pathway activated by
      F protein that led to NET production. The massive production of NETs in RSV
      infection could aggravate the inflammatory symptoms of the infection in young
      children and babies. We propose that targeting the binding of TLR-4 by F protein
      could potentially lead to novel therapeutic approaches to help control RSV
      induced inflammatory consequences and pathology of viral bronchiolitis. 

PMID- 25856629
TI  - What is the most realistic single-compartment model of spike initiation?
AB  - A large variety of neuron models are used in theoretical and computational
      neuroscience, and among these, single-compartment models are a popular kind.
      These models do not explicitly include the dendrites or the axon, and range from
      the Hodgkin-Huxley (HH) model to various flavors of integrate-and-fire (IF)
      models. The main classes of models differ in the way spikes are initiated. Which
      one is the most realistic? Starting with some general epistemological
      considerations, I show that the notion of realism comes in two dimensions:
      empirical content (the sort of predictions that a model can produce) and
      empirical accuracy (whether these predictions are correct). I then examine the
      realism of the main classes of single-compartment models along these two
      dimensions, in light of recent experimental evidence. 

PMID- 25856630
TI  - Variability in estimating shunt from single pulse oximetry measurements.
AB  - Virtual shunt describes the overall loss of O2 content between the alveolar gas
      and arterial blood. Clinicians indirectly estimate the magnitude of the virtual
      shunt by monitoring peripheral blood oxygen saturation (SpO2) using non-invasive
      pulse oximetry. An inherent limitation of this method is the variable precision
      of pulse oximeters and the non-linear relationship between virtual shunt and SpO2
      which is rarely depicted.We propose a model using a combination of basic
      physiological equations to analyze the estimation of virtual shunt from inspired
      oxygen (FiO2) and SpO2. The model emphasizes the effect of the non-linearity of
      the Hb-O2 dissociation curve. Furthermore, it accounts for the variability in
      SpO2 measurements due to the precision of pulse oximeters.The model was validated
      with experiments conducted on healthy subjects in a normobaric hypoxia chamber
      comparing the simultaneous readings from two different commercial pulse oximeters
      at FiO2 = 21% and 17%. SpO2 probability distributions calculated from the model
      were estimated. Although a variable bias (1.2-2.1%) in SpO2 between the pulse
      oximeter brands was observed, the tested pulse oximeters were both within
      tolerance specified by the manufacturers and matched the probability
      distributions from the model.The theoretical and experimental findings show that
      the estimation of virtual shunt is challenging with a single SpO2 measurement
      using pulse oximeters with tolerances of 2%. Clinical decisions must be based on
      an appreciation of these limitations. 

PMID- 25856631
TI  - What Accountable Care Organizations Can Learn from Kaiser Permanente California's
      Acute Care Strategy.

PMID- 25856632
TI  - Self-Efficacy for Sexual Risk Reduction and Partner HIV Status as Correlates of
      Sexual Risk Behavior Among HIV-Positive Adolescent Girls and Women.
AB  - Little is known about the correlates of sexual risk behavior among HIV-positive
      adolescent girls and women in the United States. This study investigates two
      potential factors related to unprotected vaginal and anal intercourse (UVAI) that
      have yet to be thoroughly studied in this group: self-efficacy for sexual risk
      reduction and partner HIV status. Data was analyzed from 331 HIV-positive
      adolescent girls and women between 12 and 24 years old who reported vaginal
      and/or anal intercourse with a male partner in the past 3 months at fifteen sites
      across the United States. Results show that overall self-efficacy (B=-0.15,
      p=0.01), self-efficacy to discuss safe sex with one's partner (B=-0.14, p=0.01),
      and self-efficacy to refuse unsafe sex (B=-0.21, p=0.01) are related to UVAI
      episodes. Participants with only HIV-positive partners or with both HIV-positive
      and HIV-negative partners showed a trend towards higher percentages of UVAI
      episodes compared to participants with only HIV-negative partners (F(2,
      319)=2.80, p=0.06). These findings point to the importance of including self
      efficacy and partner HIV status in risk-reduction research and interventions
      developed for HIV-positive adolescent girls and young women.

PMID- 25856633
TI  - Role of TGF-beta Signaling in Remodeling of Noncoronary Artery Aneurysms in
      Kawasaki Disease.
AB  - Coronary artery aneurysms (CAA) remain an important complication of Kawasaki
      disease (KD), the most common form of pediatric acquired heart disease in
      developed countries. Potentially life-threatening CAA develop in 25% of untreated
      children and 5% of children treated with high-dose intravenous immunoglobulin
      during the acute phase of the self-limited vasculitis. Noncoronary artery
      aneurysms (NCAA) in extraparenchymal, muscular arteries occur in a minority of
      patients with KD who also have CAA, yet little is understood about their
      formation and remodeling. We postulated that activation of the transforming
      growth factor-beta (TGF-beta) pathway in KD may influence formation and
      remodeling of aneurysms in iliac, femoral, and axillary arteries, the most common
      sites for NCAA. We studied a resected axillary artery from one adult and
      endarterectomy tissue from the femoral artery from a second adult, both with a
      history of CAA and NCAA following KD in infancy. Histology of the axillary artery
      aneurysm revealed destruction of the internal elastic lamina and recanalization
      of organized thrombus, while the endarterectomy specimen showed dense
      calcification and luminal myofibroblastic proliferation. Immunohistochemistry for
      molecules in the TGF-beta signaling pathway revealed increased expression of TGF
      beta2, TGF-beta receptor 2, and phosphorylated SMAD3. These findings suggest
      ongoing tissue remodeling of the aneurysms decades after the acute injury and
      demonstrate the importance of the TGF-beta signaling pathway in this process. 

PMID- 25856634
TI  - Analysis of HDAC6 and BAG3-aggresome pathways in African swine fever viral
      factory formation.
AB  - African swine fever virus (ASFV) is a double-stranded DNA virus causing a
      hemorrhagic fever disease with high mortality rates and severe economic losses in
      pigs worldwide. ASFV replicates in perinuclear sites called viral factories (VFs)
      that are morphologically similar to cellular aggresomes. This fact raises the
      possibility that both VFs and aggresomes may be the same structure. However,
      little is known about the process involved in the formation of these viral
      replication platforms. In order to expand our knowledge on the assembly of ASFV
      replication sites, we have analyzed the involvement of both canonical aggresome
      pathways in the formation of ASFV VFs: HDAC6 and BAG3. HDAC6 interacts with a
      component of the dynein motor complex (dynactin/p150Glued) and ubiquitinated
      proteins, transporting them to the microtubule-organizing center (MTOC) and
      leading to aggresome formation, while BAG3 is mediating the recruitment of non
      ubiquitinated proteins through a similar mechanism. Tubacin-mediated HDAC6
      inhibition and silencing of BAG3 pathways, individually or simultaneously, did
      not prevent ASFV VF formation. These findings show that HDAC6 and Bag3 are not
      required for VFs formation suggesting that aggresomes and VFs are not the same
      structures. However, alternative unexplored pathways may be involved in the
      formation of aggresomes.

PMID- 25856635
TI  - In ovo delivery of CpG DNA reduces avian infectious laryngotracheitis virus
      induced mortality and morbidity.
AB  - Endosomal toll-like receptor-21 and -9 sense CpG DNA activating production of pro
      inflammatory mediators with antimicrobial effects. Here, we investigated the
      induction of antiviral response of in ovo delivered CpG DNA against infectious
      laryngotracheitis virus (ILTV) infection. We found that in ovo delivered CpG DNA
      significantly reduces ILTV infection pre-hatch correlating with the expression of
      IL-1beta and increase of macrophages in lungs. As assessed in vitro, CpG DNA
      stimulated avian macrophages could be a potential source of IL-1beta and other
      pro-inflammatory mediators. Since we also found that in ovo CpG DNA delivery
      maintains increased macrophages in the lungs post-hatch, we infected the chickens
      on the day of hatch with ILTV. We found that in ovo delivered CpG DNA
      significantly reduces mortality and morbidity resulting from ILTV infection
      encountered post-hatch. Thus, CpG DNA can be a candidate innate immune stimulant
      worthy of further investigation for the control of ILTV infection in chickens. 

PMID- 25856636
TI  - A current overview of the Papaya meleira virus, an unusual plant virus.
AB  - Papaya meleira virus (PMeV) is the causal agent of papaya sticky disease, which
      is characterized by a spontaneous exudation of fluid and aqueous latex from the
      papaya fruit and leaves. The latex oxidizes after atmospheric exposure, resulting
      in a sticky feature on the fruit from which the name of the disease originates.
      PMeV is an isometric virus particle with a double-stranded RNA (dsRNA) genome of
      approximately 12 Kb. Unusual for a plant virus, PMeV particles are localized on
      and linked to the polymers present in the latex. The ability of the PMeV to
      inhabit such a hostile environment demonstrates an intriguing interaction of the
      virus with the papaya. A hypersensitivity response is triggered against PMeV
      infection, and there is a reduction in the proteolytic activity of papaya latex
      during sticky disease. In papaya leaf tissues, stress responsive proteins, mostly
      calreticulin and proteasome-related proteins, are up regulated and proteins
      related to metabolism are down-regulated. Additionally, PMeV modifies the
      transcription of several miRNAs involved in the modulation of genes related to
      the ubiquitin-proteasome system. Until now, no PMeV resistant papaya genotype has
      been identified and roguing is the only viral control strategy available.
      However, a single inoculation of papaya plants with PMeV dsRNA delayed the
      progress of viral infection.

PMID- 25856637
TI  - A Needs Assessment of Health Issues Related to Maternal Mortality Rates in
      Afghanistan: A Pilot Study.
AB  - Maternal death rates in Afghanistan were among the highest in the world during
      the reign of the Taliban. Although these figures have improved, current rates are
      still alarming. The aim of this pilot study was to develop a needs assessment of
      the major health issues related to the high maternal mortality rates in
      Afghanistan. In-depth interviews were conducted with managerial midwives,
      clinical midwives, and mothers. Results of the interviews indicate that the
      improvement in the maternal mortality rate may be attributed to the increase in
      the involvement of midwives in the birthing process. However, barriers to
      decreasing maternal mortality still exist. These include transportation, access
      to care, and sociocultural factors such as the influence of the husband and
      mother-in-law in preventing access to midwives. Therefore, any programs to
      decrease maternal mortality need to address infrastructure issues (making health
      care more accessible) and sociocultural factors (including husbands and mother-in
      laws in maternal health education). However, it should be noted that these
      findings are based on a small pilot study to help develop a larger scale need
      assessment. 

PMID- 25856638
TI  - Healthy Aging and Concerns Among Elderly Japanese: A Text Analysis Approach.
AB  - Japan is facing an unprecedented aging society. In 2013, 25.1% of the total
      population in Japan was 65 years old and over. One third of the population in
      Japan will be at least 65 years old in 2035; healthy aging is crucial for public
      health and society in Japan. Under the budget limitations of social security,
      policies and frequent policy changes have created great uncertainty and concern
      for the elderly population. Given these circumstances, we conducted questionnaire
      surveys in 2010 to examine concerns in this age-group. In 2010, we sent
      questionnaires to university graduates 65 years old and older, randomly selected
      from a list of an alumni association of 11 universities. The questionnaires were
      open-ended and asked them to write any concerns that they had about health care,
      health policy, health systems, and their future. We received 344 responses. Among
      those who responded, 271 (78.8%) respondents said that they had concerns. We
      conducted a text analysis (Trend Search-Keyword Associator 2008) and extracted
      the keywords from their responses. The keywords that were extracted frequently
      included hospitals, doctors, health-care system, health care, Japanese government
      policies, government, medical insurance system for the elderly, support,
      increase, copayment, health (their own), scarcities, and burdens. In this study,
      many elderly people in Japan are concerned about health-care expenditures, health
      care systems, and health policies. This may be caused by frequent health policy
      changes and uncertainty due to frequent administration changes such as the lack
      of clarity concerning raising the out of pocket payment rate from 10% to 20% for
      elderly people under budget constraints in Japan. Correct policy making and
      determination to eliminate the concerns from this vulnerable population in Japan
      are necessary for healthy aging. 

PMID- 25856639
TI  - Effect of the Y : B ratio on phase purity and development of thermally stable
      nano-sized Eu(+3)-doped YBO3 red phosphor using sodium borohydride.
AB  - This research focuses on the effect of the Y : B ratio on phase purity and the
      development of thermally stable 10 mol% Eu(3+)-doped YBO3 red phosphor
      nanomaterial using a novel sodium borohydride based solution precursor route. An
      equimolar concentration of Y and B leads to the development of chemically and
      thermally stable un-doped and Eu(3+)-doped YBO3 up to 1300  degrees C. An
      impurity phase, Y3BO6, was observed at a higher temperature of around 1400 
      degrees C. FESEM micrographs indicate that the particles of Eu(3+)-doped YBO3 are
      agglomerated with peanut-like morphology having an average size of ~50 nm at 800 
      degrees C, whereas the average agglomerated size was in between ~200 nm and 1.5
      MUm, at 1200  degrees C. The particles of Eu(3+)-doped YBO3 are nearly spherical
      having size ~8-10 nm at 800  degrees C and the size increases in the range of ~30
      100 nm at 1200  degrees C, as observed from TEM micrographs. In addition, the
      borohydride synthesized Eu(3+)-doped YBO3 phosphor calcined at 800  degrees C
      showed comparatively better colour purity (denoted as R/O ratio, i.e. the
      integral ratio of red to orange emission = 1.25) than the high temperature (1200 
      degrees C) calcined sample (R/O ratio = 0.97). Both the calcined powders
      indicated nearly reddish-orange colour based on calculated Commission
      Internationale de I'Eclairage (CIE) coordinates. The synthesis strategy followed
      in the current research work emphasizes the feasibility of synthesizing thermally
      stable Eu(3+)-doped YBO3 red phosphor materials by a borohydride route, which may
      be suitable for lighting applications.

PMID- 25856642
TI  - Serous macular detachment following a systemic corticosteroid injection.

PMID- 25856643
TI  - Mass obscuring the globe.

PMID- 25856644
TI  - Error in byline.
AB  - In the Observation entitled "Paravascular Inner Retinal Defect Associated With
      High Myopia or Epiretinal Membrane," published online January 22, 2015, in JAMA
      Ophthalmology (doi:10.1001/jamaophthalmol.2014.5632), the fifth author's name
      should have been given as Abdallah A. Ellabban, and in the Affiliations and
      Author Contributions as Ellabban. This article was corrected online.

PMID- 25856645
TI  - Error in group information.
AB  - In the Observation entitled "International Validation of the American Joint
      Committee on Cancer's 7th Edition Classification of Uveal Melanoma," published
      online January 2, 2015, in JAMA Ophthalmology
      (doi:10.1001/jamaophthalmol.2014.5395), the fourteenth author's name in the AJCC
      Ophthalmic Oncology Task Force Member Authors section in the Article Information
      section should have been given as Anibal M. Folgar, MD. This article was
      corrected online.

PMID- 25856646
TI  - Leukemic retinopathy.

PMID- 25856647
TI  - Epithelial ingrowth as a cause of pseudohypopyon after Descemet stripping
      automated endothelial keratoplasty.

PMID- 25856649
TI  - Scheimpflug imaging in capsular bag distention syndrome.

PMID- 25856648
TI  - Tattoo-associated uveitis.

PMID- 25856650
TI  - Anterior pyramidal cataract: a rare association.

PMID- 25856651
TI  - Syphilitic posterior uveitis.

PMID- 25856652
TI  - Temporal macular dimple in retinopathy of prematurity.

PMID- 25856653
TI  - Vision with Fuchs endothelial dystrophy.

PMID- 25856654
TI  - In vivo histologic image of ocular surface squamous neoplasia by confocal
      microscopy.

PMID- 25856655
TI  - Optical coherence tomography of an ora serrata pearl.

PMID- 25856656
TI  - Life memories and the ability to act: the meaning of autonomy and participation
      for older people when living with chronic illness.
AB  - There is a lack of knowledge about how older people living with chronic illness
      describe the meaning of autonomy and participation, indicating a risk for reduced
      autonomy and participation in their everyday life. The purpose of this study was
      to describe the meaning of autonomy and participation among older people living
      with chronic illness in accordance with their lived experience. The design was
      descriptive with a phenomenological approach guided by Giorgi's descriptive
      phenomenological psychological method. Purposive sampling was used, and 16 older
      people living with chronic illness who lived in an ordinary home participated in
      individual interviews. The findings showed that the meaning of autonomy and
      participation among the older people emerged when it was challenged and evoked
      emotional considerations of the lived experience of having a chronic illness. It
      involved living a life apart, yet still being someone who is able, trustworthy
      and given responsibility--still being seen and acknowledged. The meaning of
      autonomy and participation was derived through life memories and used by the
      older people in everyday life for adjustment or adaption to the present life and
      the future. Our conclusion is that autonomy and participation were considered in
      relation to older people's life memories in the past, in their present situation
      and also their future wishes. Ability or disability is of less importance than
      the meaning of everyday life among older people. We suggest using fewer labels
      for limitations in everyday life when caring for older people and more use of the
      phrase 'ability to act' in different ways, based on older people's descriptions
      of the meaning of autonomy and participation.

PMID- 25856657
TI  - Think Again: First Do No Harm: A Case of Munchausen Syndrome by Proxy.
AB  - Apparent life-threatening events caused by Munchausen syndrome by proxy (MSP) are
      rare but difficult to resolve medically. Failure to properly diagnose MSP can
      lead to further abuse by the caregiver and increase the risk of complications due
      to long hospital stays and invasive tests. In this paper, we describe our
      experiences with a baby who ended up being diagnosed with MSP, including our
      initial failure to find a pathology, delay of MSP diagnosis, our growing
      suspicion of MSP despite technical setbacks, our actions after we confirmed MSP
      as the cause of his hospitalizations. We also describe the difficulties of
      diagnosing MSP compared to more traditional problems and explain a series of
      precautions and guidelines to help detect it in a timely manner. 

PMID- 25856658
TI  - Mind and body therapy for fibromyalgia.
AB  - BACKGROUND: Mind-body interventions are based on the holistic principle that
      mind, body and behaviour are all interconnected. Mind-body interventions
      incorporate strategies that are thought to improve psychological and physical
      well-being, aim to allow patients to take an active role in their treatment, and
      promote people's ability to cope. Mind-body interventions are widely used by
      people with fibromyalgia to help manage their symptoms and improve well-being.
      Examples of mind-body therapies include psychological therapies, biofeedback,
      mindfulness, movement therapies and relaxation strategies. OBJECTIVES: To review
      the benefits and harms of mind-body therapies in comparison to standard care and
      attention placebo control groups for adults with fibromyalgia, post-intervention
      and at three and six month follow-up. SEARCH METHODS: Electronic searches of the
      Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid), EMBASE
      (Ovid), PsycINFO (Ovid), AMED (EBSCO) and CINAHL (Ovid) were conducted up to 30
      October 2013. Searches of reference lists were conducted and authors in the field
      were contacted to identify additional relevant articles. SELECTION CRITERIA: All
      relevant randomised controlled trials (RCTs) of mind-body interventions for
      adults with fibromyalgia were included. DATA COLLECTION AND ANALYSIS: Two authors
      independently selected studies, extracted the data and assessed trials for low,
      unclear or high risk of bias. Any discrepancy was resolved through discussion and
      consensus. Continuous outcomes were analysed using mean difference (MD) where the
      same outcome measure and scoring method was used and standardised mean difference
      (SMD) where different outcome measures were used. For binary data standard
      estimation of the risk ratio (RR) and its 95% confidence interval (CI) was used.
      MAIN RESULTS: Seventy-four papers describing 61 trials were identified, with 4234
      predominantly female participants. The nature of fibromyalgia varied from mild to
      severe across the study populations. Twenty-six studies were classified as having
      a low risk of bias for all domains assessed. The findings of mind-body therapies
      compared with usual care were prioritised.There is low quality evidence that in
      comparison to usual care controls psychological therapies have favourable effects
      on physical functioning (SMD -0.4, 95% CI -0.6 to -0.3, -7.5% absolute change, 2
      point shift on a 0 to 100 scale), pain (SMD -0.3, 95% CI -0.5 to -0.2, -3.5%
      absolute change, 2 point shift on a 0 to 100 scale) and mood (SMD -0.5, 95% CI 
      0.6 to -0.3, -4.8% absolute change, 3 point shift on a 20 to 80 scale). There is
      very low quality evidence of more withdrawals in the psychological therapy group
      in comparison to usual care controls (RR 1.38, 95% CI 1.12 to 1.69, 6% absolute
      risk difference). There is lack of evidence of a difference between the number of
      adverse events in the psychological therapy and control groups (RR 0.38, 95% CI
      0.06 to 2.50, 4% absolute risk difference).There was very low quality evidence
      that biofeedback in comparison to usual care controls had an effect on physical
      functioning (SMD -0.1, 95% CI -0.4 to 0.3, -1.2% absolute change, 1 point shift
      on a 0 to 100 scale), pain (SMD -2.6, 95% CI -91.3 to 86.1, -2.6% absolute
      change) and mood (SMD 0.1, 95% CI -0.3 to 0.5, 1.9% absolute change, less than 1
      point shift on a 0 to 90 scale) post-intervention. In view of the quality of
      evidence we cannot be certain that biofeedback has a little or no effect on these
      outcomes. There was very low quality evidence that biofeedback led to more
      withdrawals from the study (RR 4.08, 95% CI 1.43 to 11.62, 20% absolute risk
      difference). No adverse events were reported.There was no advantage observed for
      mindfulness in comparison to usual care for physical functioning (SMD -0.3, 95%
      CI -0.6 to 0.1, -4.8% absolute change, 4 point shift on a scale 0 to 100), pain
      (SMD -0.1, CI -0.4 to 0.3, -1.3% absolute change, less than 1 point shift on a 0
      to 10 scale), mood (SMD -0.2, 95% CI -0.5 to 0.0, -3.7% absolute change, 2 point
      shift on a 20 to 80 scale) or withdrawals (RR 1.07, 95% CI 0.67 to 1.72, 2%
      absolute risk difference) between the two groups post-intervention. However, the
      quality of the evidence was very low for pain and moderate for mood and number of
      withdrawals. No studies reported any adverse events.Very low quality evidence
      revealed that movement therapies in comparison to usual care controls improved
      pain (MD -2.3, CI -4.2 to -0.4, -23% absolute change) and mood (MD -9.8, 95% CI 
      18.5 to -1.2, -16.4% absolute change) post-intervention. There was no advantage
      for physical functioning (SMD -0.2, 95% CI -0.5 to 0.2, -3.4% absolute change, 2
      point shift on a 0 to 100 scale), participant withdrawals (RR 1.95, 95% CI 1.13
      to 3.38, 11% absolute difference) or adverse events (RR 4.62, 95% CI 0.23 to
      93.92, 4% absolute risk difference) between the two groups, however rare adverse
      events may include worsening of pain.Low quality evidence revealed that
      relaxation based therapies in comparison to usual care controls showed an
      advantage for physical functioning (MD -8.3, 95% CI -10.1 to -6.5, -10.4%
      absolute change) and pain (SMD -1.0, 95% CI -1.6 to -0.5, -3.5% absolute change,
      2 point shift on a 0 to 78 scale) but not for mood (SMD -4.4, CI -14.5 to 5.6, 
      7.4% absolute change) post-intervention. There was no difference between the
      groups for number of withdrawals (RR 4.40, 95% CI 0.59 to 33.07, 31% absolute
      risk difference) and no adverse events were reported. AUTHORS' CONCLUSIONS:
      Psychological interventions therapies may be effective in improving physical
      functioning, pain and low mood for adults with fibromyalgia in comparison to
      usual care controls but the quality of the evidence is low. Further research on
      the outcomes of therapies is needed to determine if positive effects identified
      post-intervention are sustained. The effectiveness of biofeedback, mindfulness,
      movement therapies and relaxation based therapies remains unclear as the quality
      of the evidence was very low or low. The small number of trials and inconsistency
      in the use of outcome measures across the trials restricted the analysis.

PMID- 25856659
TI  - Clinical perspectives: practical insights from clinical experience with
      cabazitaxel in Australia.
AB  - Prostate cancer, and in particular the management options for patients with
      metastatic castration-resistant prostate cancer (mCRPC), remains an important
      health issue. The approval of cabazitaxel provides a new treatment option for
      patients who have progressed despite docetaxel therapy. Clinical use of
      cabazitaxel in mCRPC is based on the results of the TROPIC study, which
      demonstrated an approximately 30% reduction in the risk of death compared with
      mitoxantrone. In this paper, we draw on accumulating clinical experience with
      cabazitaxel in Australia to discuss important questions such as how to select the
      right patient for treatment and how to proactively prevent and manage toxicities
      associated with this therapy. Recognizing the need for a multidisciplinary
      approach to patient care, opinion and insight has been sought from medical
      oncologists, nurses and pharmacists. While lack of trial data means that a number
      of questions remain unanswered, local clinical experience has helped to guide
      treatment decisions and refine management protocols. Appropriate patient
      selection, careful ongoing monitoring and proactive management of adverse events
      will ensure optimal treatment of patients. Nurses in particular play an important
      role in educating patients and identifying patients at increased risk of
      developing adverse events with cabazitaxel. The oncology team must work together
      to educate patients; taking a proactive approach to issues such as adverse events
      will help maximize the clinical outcome of cabazitaxel treatment and impact
      positively on the patient's quality of life. 

PMID- 25856660
TI  - Correlations between acoustic rhinometry, subjective symptoms, and endoscopic
      findings in symptomatic children with nasal obstruction.
AB  - IMPORTANCE: Nasal obstruction is common in children and difficult to quantify
      objectively. Symptom quantification is paramount for surgical and medical
      decision making. Acoustic rhinometry is a relatively new technique aimed at the
      objective assessment of nasal obstruction. There is no standardized method for
      the objective assessment of the pediatric nasal airway. OBJECTIVE: To explore the
      correlations between acoustic rhinometry (AR), subjective symptoms, and
      endoscopic findings in children presenting with nasal obstruction. DESIGN,
      SETTING, AND PARTICIPANTS: A cross-sectional, exploratory, diagnostic study of
      prospectively collected data from a multidisciplinary airway clinic (pulmonology,
      orthodontics, and otolaryngology) database at a tertiary academic referral
      center. Data were collected over a 2-year period (2010-2012) from 65 nonsyndromic
      children (38 boys) 7 years and older (mean [SD] age, 10.3 [2.5] years [range, 7
      14 years]), presenting with persistent nasal obstructive symptoms for at least 1
      year, without signs and symptoms of sinus disease. INTERVENTIONS: We collected
      patient demographics and medical history information including allergy, asthma,
      and sleep-disordered breathing. Subjective nasal obstruction was scored using a
      visual analog scale (VAS). Sleep-disordered breathing was assessed using
      overnight pulse oximetry. The adenoid size, septal position, and visual severity
      of chronic rhinitis (endoscopic rhinitis score [ERS]) were rated on nasal
      endoscopy by 2 independent reviewers and validated by agreement. Acoustic
      rhinometry (AR) was undertaken before and after use of a decongestant. MAIN
      OUTCOMES AND MEASURES: Correlation and multiple regression analyses were
      performed to explore interrelationships between subjective nasal obstruction VAS,
      AR, and nasal endoscopy. RESULTS: Among the 65 patients, 28 (43%) had symptoms of
      sleep-disordered breathing, 14 (22%) had allergic rhinitis, 10 (15%) had asthma,
      27 (41%) had grade 3 or 4 adenoidal obstruction, 28 (43%) had an ERS of 2, 6 (9%)
      had an ERS of 3, and 19 (29%) had septal deviation. Significant correlations were
      found between subjective nasal obstruction VAS score and ERS (r = -0.364, P =
      .003), ERS and minimal cross-sectional area before decongestion (r = -0.278, P =
      .03), and adenoid size and calculated nasal resistance after decongestion (r =
      0.430, P < .001). Multiple regression analysis showed that the ERS was the only
      significant predictor of VAS score (beta of -22.089; 95% CI, -35.56 to -8.61 [P =
      .002]). No predictors were identified for AR variables. CONCLUSIONS AND
      RELEVANCE: Among the evaluated tools, endoscopy appears to be the most reliable
      tool to estimate the degree of subjective nasal symptoms.

PMID- 25856663
TI  - Validation of a new extraction device for measuring faecal calprotectin in
      inflammatory bowel disease, and comparison to established extraction methods.
AB  - OBJECTIVE: Faecal (f-) calprotectin is a widely used surrogate marker of
      intestinal inflammation. F-calprotectin analysis is labour demanding partly due
      to a time consuming extraction step. The aim of this project was to validate a
      new extraction method for f-calprotectin. MATERIAL AND METHODS: A prospective
      multicentre study included 135 patients with an established diagnosis of
      inflammatory bowel disease. The patients submitted a faeces sample, which was
      extracted with both the conventional method at the participating laboratory and
      the new extraction device. The extracts were analyzed by an automated ELISA
      instrument. RESULTS: Method comparison of the traditional method and the new
      device showed a slope of 1.01 (0.93-1.07) with intercept of - 2.2 (- 4.9-0.6).
      The Spearman rank correlation coefficient was 0.96. CONCLUSIONS: The new
      extraction device is a reliable and time saving alternative to the conventional
      extraction method.

PMID- 25856664
TI  - Benefits of microprocessor-controlled prosthetic knees to limited community
      ambulators: systematic review.
AB  - The benefits of microprocessor-controlled prosthetic knees (MPKs) have been well
      established in community ambulators (Medicare Functional Classification Level
      [MFCL]-3) with a transfemoral amputation (TFA). A systematic review of the
      literature was performed to analyze whether limited community ambulators (MFCL-2)
      may also benefit from using an MPK in safety, performance-based function and
      mobility, and perceived function and satisfaction. We searched 10 scientific
      databases for clinical trials with MPKs and identified six publications with 57
      subjects with TFA and MFCL-2 mobility grade. Using the criteria of a Cochrane
      Review on prosthetic components, we rated methodological quality moderate in four
      publications and low in two publications. MPK use may significantly reduce
      uncontrolled falls by up to 80% as well as significantly improve indicators of
      fall risk. Performance-based outcome measures suggest that persons with MFCL-2
      mobility grade may be able to walk about 14% to 25% faster on level ground, be
      around 20% quicker on uneven surfaces, and descend a slope almost 30% faster when
      using an MPK. The results of this systematic review suggest that trial fittings
      may be used to determine whether or not individuals with TFA and MFCL-2 mobility
      grade benefit from MPK use. Criteria for patient selection and assessment of
      trial fitting success or failure are proposed. 

PMID- 25856665
TI  - PET imaging with the non-pure positron emitters: (55)Co, (86)Y and (124)I.
AB  - PET/CT with non-pure positron emitters is a highly valuable tool in immuno-PET
      and for pretherapeutic dosimetry. However, imaging is complicated by prompt gamma
      coincidences (PGCs) that add an undesired background activity to the images. Time
      of-flight (TOF) reconstruction improves lesion detectability in (18)F-PET and can
      potentially also improve the signal-to-noise ratio in images acquired with non
      pure positron emitters. Using the GE Discovery 690 PET/CT system, we evaluated
      the image quality with (55)Co, (86)Y and (124)I, and the effect of PGC-correction
      and TOF-reconstruction on image quality and quantitation in a series of phantom
      studies. PET image quality and quantitation for all isotopes were significantly
      affected by PGCs. The effect was most severe with (86)Y, and less, but
      comparable, with (55)Co and (124)I. PGC-correction improved the image quality and
      the quantitation accuracy dramatically for all isotopes, especially when the
      activity was limited to a few hot lesions in a warm background. In imaging
      situations, where high levels of activity were present in the background,
      activity concentrations were overestimated. TOF-reconstruction improved image
      quality in isolated lesions but worsened the accuracy of quantitation and
      uniformity in homogeneous activity distributions. Better modelling of PGCs in the
      scatter correction can potentially improve the situation. 

PMID- 25856666
TI  - Structure-Related Mode-of-Action Differences of Anticancer Organoruthenium
      Complexes with beta-Diketonates.
AB  - A series of organoruthenium(II) chlorido complexes with fluorinated O,O-ligands
      [(eta(6)-p-cymene)Ru(F3C-acac-Ar)Cl] (1a-6a) and their respective 1,3,5-triaza-7
      phosphaadamantane (pta) derivatives [(eta(6)-p-cymene)Ru(F3C-acac-Ar)pta]PF6 (1b
      6b) were synthesized and fully characterized in both solution and solid state.
      All complexes were inactive against nonmalignant keratinocytes but displayed
      variable activity against cancer cell models (ovarian, osteosarcoma). Compounds
      with a ligand containing the 4-chlorophenyl substituent (6a and 6b) exhibited the
      strongest anticancer effects. Despite a marginally lower cellular Ru accumulation
      compared to the chlorido complexes, pta analogues showed higher activity
      especially in the osteosarcoma model. Reduction of glutathione levels by
      buthionine sulfoximine (BSO) significantly enhanced the activity of all compounds
      with the most pronounced effects being observed for the pta series resulting in
      IC50 values down to the nanomolar range. While all chlorido complexes potently
      induce reactive oxygen species, DNA damage, and apoptosis, the respective pta
      compounds widely lacked ROS production but blocked cell cycle progression in
      G0/G1 phase. 

PMID- 25856667
TI  - Translating rare-disease therapies into improved care for patients and families:
      what are the right outcomes, designs, and engagement approaches in health-systems
      research?
AB  - There is a need for research to understand and improve health systems for rare
      diseases in order to ensure that new, efficacious therapies developed through
      basic and early translational science lead to real benefits for patients. Such
      research must (i) focus on appropriate patient-oriented outcomes, (ii) include
      robust study designs that can accommodate real-world decision priorities, and
      (iii) involve effective stakeholder-engagement strategies. For transformative
      therapies, study outcomes will need to shift toward longer-term goals in
      recognition of success in preventing catastrophic outcomes. For incremental
      therapies, outcomes should be selected in recognition of the impact of care on
      quality of life for patients and families. To generate new evidence, we suggest
      that hybrid study designs integrating elements of practice-based observational
      research and pragmatic trials hold the most promise for addressing priorities
      such as minimizing bias, accounting for cointerventions, identifying long-term
      impacts, and considering clinical heterogeneity. To effectively engage with
      stakeholders, a knowledge exchange infrastructure is needed to foster
      collaboration among patients with rare diseases and their families, health-care
      providers, researchers, and policy decision makers. A key priority for these
      groups must be collaboration toward a shared understanding of the outcomes that
      are of most relevance to the facilitation of patient-centered care.

PMID- 25856669
TI  - Family decision maker perspectives on the return of genetic results in biobanking
      research.
AB  - PURPOSE: There are many ethical considerations regarding the return of genetic
      results to biobanking participants, especially when biobanks collect samples from
      deceased organ and tissue donors that require the authorization of a family
      decision maker (FDM). This article explores FDM knowledge and opinions regarding
      return of genetic results in the context of the Genotype-Tissue Expression (GTEx)
      Project, which does not return results to participants. METHODS: Data collection
      included a survey completed by Organ Procurement Organization requesters (n = 22)
      and semistructured telephone interviews with FDM (n = 55). RESULTS: Nearly every
      FDM wanted some form of genetic results returned. Information regarding treatable
      diseases (94.3%) and diseases that could affect their children (84.9%) were more
      desirable than that regarding untreatable diseases (71.7%). Sixty percent of FDMs
      understood that GTEx would not return genetic results. FDMs were four times more
      likely to have correct knowledge of the GTEx policy when their GTEx requester
      reported discussing the topic with them. CONCLUSION: FDMs from the GTEx project
      were interested in receiving genetic test results. Marked changes in the
      infrastructure of the GTEx would be required to alter the policy. Regardless,
      care must be taken to ensure that the return policy is clearly communicated with
      FDMs to dispel misconceptions.Genet Med 18 1, 82-88.

PMID- 25856668
TI  - PMS2 monoallelic mutation carriers: the known unknown.
AB  - Germ-line mutations in MLH1, MSH2, MSH6, and PMS2 have been shown to cause Lynch
      syndrome. The penetrance of the cancer and tumor spectrum has been repeatedly
      studied, and multiple professional societies have proposed clinical management
      guidelines for affected individuals. Several studies have demonstrated a reduced
      penetrance for monoallelic carriers of PMS2 mutations compared with the other
      mismatch repair (MMR) genes, but clinical management guidelines have largely
      proposed the same screening recommendations for all MMR gene carriers. The
      authors considered whether enough evidence existed to propose new screening
      guidelines specific to PMS2 mutation carriers with regard to age at onset and
      frequency of colonic screening. Published reports of PMS2 germ-line mutations
      were combined with unpublished cases from the authors' research registries and
      clinical practices, and a discussion of potential modification of cancer
      screening guidelines was pursued. A total of 234 monoallelic PMS2 mutation
      carriers from 170 families were included. Approximately 8% of those with
      colorectal cancer (CRC) were diagnosed before age 30, and each of these tumors
      presented on the left side of the colon. As it is currently unknown what causes
      the early onset of CRC in some families with monoallelic PMS2 germline mutations,
      the authors recommend against reducing cancer surveillance guidelines in families
      found having monoallelic PMS2 mutations in spite of the reduced penetrance.Genet
      Med 18 1, 13-19. 

PMID- 25856670
TI  - Outcomes of four patients with homocysteine remethylation disorders detected by
      newborn screening.
AB  - PURPOSE: We evaluated the clinical outcome in homocysteine remethylation
      disorders following newborn screening (NBS) and initiation of early specific
      treatment. METHODS: Five patients with remethylation disorders were included in
      this study. RESULTS: Two asymptomatic patients (one with cblG and one with cblE)
      were identified by NBS using an approach that combines a postanalytical
      interpretive tool (available on the Region 4 Stork (R4S) collaborative project
      website, http://www.clir-r4s.org) and a second-tier test for total homocysteine
      determination. Both the initial screening and the second-tier test are performed
      on the same blood spot, with no additional patient contact, resulting in no false
      positive outcomes. Two additional patients with methylenetetrahydrofolate
      reductase deficiency were detected by NBS using low methionine as a marker.
      Although already symptomatic despite the early diagnosis, the latter two patients
      greatly improved with treatment and their outcomes are compared with that of
      another patient with methylenetetrahydrofolate reductase deficiency and
      significant morbidity who was diagnosed clinically at 3 months of age.
      CONCLUSION: Early detection by NBS and timely and specific treatment considerably
      improve at least short-term outcomes of homocysteine remethylation disorders.
      When a remethylation disorder is suspected, group-specific treatment could be
      started prior to the completion of in vitro confirmatory testing because all
      disorders from this group require similar intervention.

PMID- 25856671
TI  - Frequency and spectrum of actionable pathogenic secondary findings in 196 Korean
      exomes.
AB  - PURPOSE: One of the biggest challenges of exome and genome sequencing in the era
      of genomic medicine is the identification and reporting of secondary findings. In
      this study we investigated the frequency and spectrum of actionable pathogenic
      secondary findings in Korean exomes. METHODS: Data from 196 Korean exomes were
      screened for variants from a list of 56 genes recommended by the American College
      of Medical Genetics and Genomics (ACMG) for return of secondary findings.
      Identified variants were classified according to the evidence-based guidelines
      reached by a joint consensus of the ACMG and the Association for Molecular
      Pathology. RESULTS: Among the 196 exomes, which were from 100 healthy controls
      and 96 patients with suspected genetic disorders, 11 variants in 13 individuals
      were found to be pathogenic or likely pathogenic. We estimated that the frequency
      of actionable pathogenic secondary findings was 7% for the control subjects
      (7/100) and 6% for the patients with disease (6/96). For one autosomal-recessive
      disease, four individuals exhibited either one pathogenic or one likely
      pathogenic variant of the MUTYH gene, leading to a carrier frequency of 2%
      (4/196). CONCLUSION: Secondary findings are not uncommon in Korean exomes.

PMID- 25856672
TI  - Proxy markers of serum retinol concentration, used alone and in combination, to
      assess population vitamin A status in Kenyan children: a cross-sectional study.
AB  - BACKGROUND: Serum retinol concentration determined by high-performance liquid
      chromatography (HPLC) is recommended by the World Health Organization to assess
      population vitamin A status. This assay is expensive, technically demanding and
      rarely available in developing countries. Our objective was a) to assess the
      diagnostic performance of proxy markers in detecting vitamin A deficiency and b)
      to derive decision rules based on these markers to estimate vitamin A deficiency
      prevalence. METHODS: A survey was conducted in 15 rural primary schools in
      Eastern Province, Kenya, with 375 children aged 6 to 12 years (25 randomly
      selected per school). Serum retinol concentration <0.70 MUmol/L by HPLC was used
      to define vitamin A deficiency. Proxy markers for vitamin A deficiency were serum
      concentrations of retinol binding protein (RBP), transthyretin, retinol measured
      by fluorometry and RBP:transthyretin molar ratio. RESULTS: The prevalence of
      vitamin A deficiency (HPLC) was 18%. Transthyretin and RBP showed the best
      diagnostic performance individually, with area-under-the-curve (AUC) values of
      0.96 and 0.93. When combined, and with C-reactive protein added, the AUC
      increased to 0.98. A simple decision rule {(-15.277 * [RBP, MUmol/L] - 7.013 *
      [Transthyretin, MUmol/L] + 0.367 * [C-reactive protein, mg/L] + 24.714) > 0.496}
      yielded prevalence estimates of vitamin A deficiency that is unbiased by
      diagnostic error. CONCLUSIONS: The combination of transthyretin, RBP and C
      reactive protein concentrations could eventually replace retinol concentration by
      HPLC in resource-poor settings as the preferred method to assess the population
      burden of vitamin A deficiency.

PMID- 25856673
TI  - Genome-wide expression in visceral adipose tissue from obese prepubertal
      children.
AB  - Characterization of the genes expressed in adipose tissue (AT) is key to
      understanding the pathogenesis of obesity and to developing treatments for this
      condition. Our objective was to compare the gene expression in visceral AT (VAT)
      between obese and normal-weight prepubertal children. A total of fifteen obese
      and sixteen normal-weight children undergoing abdominal elective surgery were
      selected. RNA was extracted from VAT biopsies. Microarray experiments were
      independently performed for each sample (six obese and five normal-weight
      samples). Validation by quantitative PCR (qPCR) was performed on an additional 10
      obese and 10 normal-weight VAT samples. Of 1276 differentially expressed genes (p
      < 0.05), 245 were more than two-fold higher in obese children than in normal
      weight children. As validated by qPCR, expression was upregulated in genes
      involved in lipid and amino acid metabolism (CES1, NPRR3 and BHMT2), oxidative
      stress and extracellular matrix regulation (TNMD and NQO1), adipogenesis (CRYAB
      and AFF1) and inflammation (ANXA1); by contrast, only CALCRL gene expression was
      confirmed to be downregulated. In conclusion, this study in prepubertal children
      demonstrates the up- and down-regulation of genes that encode molecules that were
      previously proposed to influence the pathogenesis of adulthood obesity, as well
      as previously unreported dysregulated genes that may be candidate genes in the
      aetiology of obesity. 

PMID- 25856674
TI  - Investigation of Forster resonance energy transfer (FRET) and competition of
      fluorescent dyes on DNA microparticles.
AB  - Fluorescent labeling is widely used to investigate the structural stability and
      changes to DNA nano- and microstructures. Despite this, the conventional method
      for observing DNA structures has several limitations in terms of cost-efficiency.
      This paper introduces a DNA spherical particle stained with DNA intercalating
      dyes (SYBR Green and SYTOX Orange) as tracers and reports the interaction between
      multiple dyes. The interference between the dyes was analyzed in terms of Forster
      resonance energy transfer (FRET) and competition. The changes in the fluorescence
      intensity by FRET were uniform, regardless of the sequence. The competition
      effect could occur when several dyes were added simultaneously. These properties
      are expected to help in the design of multicolor tracers in bioimaging and
      environmental applications. 

PMID- 25856675
TI  - Biological mechanisms underlying the ultraviolet radiation-induced formation of
      skin wrinkling and sagging I: reduced skin elasticity, highly associated with
      enhanced dermal elastase activity, triggers wrinkling and sagging.
AB  - The repetitive exposure of skin to ultraviolet B (UVB) preferentially elicits
      wrinkling while ultraviolet A (UVA) predominantly elicits sagging. In chronically
      UVB or UVA-exposed rat skin there is a similar tortuous deformation of elastic
      fibers together with decreased skin elasticity, whose magnitudes are greater in
      UVB-exposed skin than in UVA-exposed skin. Comparison of skin elasticity with the
      activity of matrix metalloproteinases (MMPs) in the dermis of ovariectomized rats
      after UVB or UVA irradiation demonstrates that skin elasticity is more
      significantly decreased in ovariectomized rats than in sham-operated rats, which
      is accompanied by a reciprocal increase in elastase activity but not in the
      activities of collagenases I or IV. Clinical studies using animal skin and human
      facial skin demonstrated that topical treatment with a specific inhibitor or an
      inhibitory extract of skin fibroblast-derived elastase distinctly attenuates UVB
      and sunlight-induced formation of wrinkling. Our results strongly indicated that
      the upregulated activity of skin fibroblast-derived elastase plays a pivotal role
      in wrinkling and/or sagging of the skin via the impairment of elastic fiber
      configuration and the subsequent loss of skin elasticity. 

PMID- 25856677
TI  - Inflammatory biomarkers as differential predictors of antidepressant response.
AB  - Although antidepressants are generally effective in the treatment of major
      depressive disorder (MDD), it can still take weeks before patients feel the full
      antidepressant effects. Despite the efficacy of standard treatments,
      approximately two-thirds of patients with MDD fail to respond to pharmacotherapy.
      Therefore, the identification of blood biomarkers that can predict the treatment
      response to antidepressants would be highly useful in order to improve this
      situation. This article discusses inflammatory molecules as predictive biomarkers
      for antidepressant responses to several classes of antidepressants, including the
      N-methyl-d-aspartate (NMDA) receptor antagonist ketamine. 

PMID- 25856676
TI  - Biological mechanisms underlying the ultraviolet radiation-induced formation of
      skin wrinkling and sagging II: over-expression of neprilysin plays an essential
      role.
AB  - Our previous studies strongly indicated that the up-regulated activity of skin
      fibroblast-derived elastase plays a pivotal role in wrinkling and/or sagging of
      the skin via the impairment of elastic fiber configuration and the subsequent
      loss of skin elasticity. Fortunately, we succeeded in identifying human skin
      fibroblast-derived elastase as a previously known enzyme, neprilysin or neutral
      endopeptidase (NEP). We have also characterized epithelial-mesenchymal paracrine
      cytokine interactions between UVB-exposed-keratinocytes and dermal fibroblasts
      and found that interleukin-1alpha and granulocyte macrophage colony stimulatory
      factor (GM-CSF) are intrinsic cytokines secreted by UVB-exposed keratinocytes
      that stimulate the expression of neprilysin by fibroblasts. On the other hand,
      direct UVA exposure of human fibroblasts significantly stimulates the secretion
      of IL-6 and also elicits a significant increase in the gene expression of matrix
      metallo-protease(MMP)-1 as well as neprilysin (to a lesser extent), which is
      followed by distinct increases in their protein and enzymatic activity levels.
      Direct UVA exposure of human keratinocytes also stimulates the secretion of IL-6,
      IL-8 and GM-CSF but not of IL-1 and endothelin-1. These findings suggest that GM
      CSF secreted by UVA-exposed keratinocytes as well as IL-6 secreted by UVA-exposed
      dermal fibroblasts play important and additional roles in UVA-induced sagging and
      wrinkling by up-regulation of neprilysin and MMP-1, respectively, in dermal
      fibroblasts. 

PMID- 25856679
TI  - Genetic variability and population structure of Salvia lachnostachys:
      implications for breeding and conservation programs.
AB  - The genetic diversity and population structure of Salvia lachnostachys Benth were
      assessed. Inter Simple Sequence Repeat (ISSR) molecular markers were used to
      investigate the restricted distribution of S. lachnostachys in Parana State,
      Brazil. Leaves of 73 individuals representing three populations were collected.
      DNA was extracted and submitted to PCR-ISSR amplification with nine tested
      primers. Genetic diversity parameters were evaluated. Our analysis indicated
      95.6% polymorphic loci (stress value 0.02) with a 0.79 average Simpson's index.
      The Nei-Li distance dendrogram and principal component analysis largely recovered
      the geographical origin of each sample. Four major clusters were recognized
      representing each collected population. Nei's gene diversity and Shannon's
      information index were 0.25 and 0.40 respectively. As is typical for outcrossing
      herbs, the majority of genetic variation occurred at the population level
      (81.76%). A high gene flow (Nm = 2.48) was observed with a correspondingly low
      fixation index. These values were generally similar to previous studies on
      congeneric species. The results of principal coordinate analysis (PCA) and of
      arithmetic average (UPGMA) were consistent and all three populations appear
      distinct as in STRUCTURE analysis. In addition, this analysis indicated a
      majority intrapopulation genetic variation. Despite the human pressure on natural
      populations our study found high levels of genetic diversity for S.
      lachnostachys. This was the first molecular assessment for this endemic species
      with medicinal proprieties and the results can guide for subsequent
      bioprospection, breeding programs or conservation actions. 

PMID- 25856680
TI  - The photodynamic antibacterial effects of silicon phthalocyanine (Pc) 4.
AB  - The emergence of antibiotic-resistant strains in facultative anaerobic Gram
      positive coccal bacteria, such as methicillin-resistant Staphylococcus aureus
      (MRSA), is a global health issue. Typically, MRSA strains are found associated
      with institutions like hospitals but recent data suggest that they are becoming
      more prevalent in community-acquired infections. It is thought that the incidence
      and prevalence of bacterial infections will continue to increase as (a) more
      frequent use of broad-spectrum antibiotics and immunosuppressive medications; (b)
      increased number of invasive medical procedures; and (c) higher incidence of
      neutropenia and HIV infections. Therefore, more optimal treatments, such as
      photodynamic therapy (PDT), are warranted. PDT requires the interaction of light,
      a photosensitizing agent, and molecular oxygen to induce cytotoxic effects. In
      this study, we investigated the efficacy and characterized the mechanism of
      cytotoxicity induced by photodynamic therapy sensitized by silicon phthalocyanine
      (Pc) 4 on (a) methicillin-sensitive Staphylococcus aureus (MSSA) (ATCC 25923);
      (b) community acquired methicillin-resistant Staphylococcus aureus (CA-MRSA)
      (ATCC 43300); and (c) hospital acquired methicillin-resistant Staphylococcus
      aureus (HA-MRSA) (PFGE type 300). Our data include confocal image analysis, which
      confirmed that Pc 4 is taken up by all S. aureus strains, and viable cell
      recovery assay, which showed that concentrations as low as 1.0 MUM Pc 4 incubated
      for 3 h at 37  degrees C followed by light at 2.0 J/cm2 can reduce cell survival
      by 2-5 logs. These results are encouraging, but before PDT can be utilized as an
      alternative treatment for eradicating resistant strains, we must first
      characterize the mechanism of cell death that Pc 4-based PDT employs in
      eliminating these pathogens. 

PMID- 25856678
TI  - Mushroom lectins: specificity, structure and bioactivity relevant to human
      disease.
AB  - Lectins are non-immunoglobulin proteins that bind diverse sugar structures with a
      high degree of selectivity. Lectins play crucial role in various biological
      processes such as cellular signaling, scavenging of glycoproteins from the
      circulatory system, cell-cell interactions in the immune system, differentiation
      and protein targeting to cellular compartments, as well as in host defence
      mechanisms, inflammation, and cancer. Among all the sources of lectins, plants
      have been most extensively studied. However, more recently fungal lectins have
      attracted considerable attention due to their antitumor, antiproliferative and
      immunomodulatory activities. Given that only 10% of mushroom species are known
      and have been taxonomically classified, mushrooms represent an enormous
      unexplored source of potentially useful and novel lectins. In this review we
      provide an up-to-date summary on the biochemical, molecular and structural
      properties of mushroom lectins, as well as their versatile applications
      specifically focusing on mushroom lectin bioactivity. 

PMID- 25856682
TI  - High-Dose Inhaled Salbutamol Does Not Improve 10-km Cycling Time Trial
      Performance.
AB  - BACKGROUND: beta2-agonists are on the World Anti-Doping Agency's list of
      prohibited substances; however, athletes are allowed to treat symptoms of
      exercise-induced bronchoconstriction with a maximal daily dose of 1600 MUg of
      salbutamol when taken by inhalation. PURPOSE: This study aimed to investigate
      whether 1600 MUg of salbutamol leads to enhanced time trial performance in
      trained, competitive male cyclists with and without exercise-induced
      bronchoconstriction on the basis of inhaled dose per kilogram of body weight.
      METHODS: In a randomized crossover design, 20 trained male cyclists (eight with
      positive eucapnic voluntary hyperpnea challenge (EVH+) and 12 with negative EVH
      challenge (EVH-) performed two simulated 10-km time trials on a cycle ergometer
      30 min after the inhalation of either 1600 MUg of salbutamol or placebo. Lung
      function, assessed by forced expiratory volume in 1 s (FEV1), was measured
      immediately before and 15 min after inhalation. The main performance outcome was
      mean power output. RESULTS: After the inhalation of salbutamol, FEV1 was
      significantly increased by 6.4% (4.9%) versus 1.0% (4.4%) with placebo (P <
      0.001). Despite this increase in FEV1, mean power output during the salbutamol
      time trial was not increased regardless of relative dose per kilogram of body
      weight and asthma status. Mean heart rate (P = 0.01), respiratory rate (P =
      0.01), minute ventilation (P = 0.03) and perceived leg discomfort (P = 0.03) were
      significantly increased in the salbutamol condition. CONCLUSIONS: The inhalation
      of 1600 MUg salbutamol improved FEV1 regardless of EVH status but did not improve
      10-km time trial performance in trained competitive male cyclists regardless of
      relative dose per kilogram of body weight or EVH status. Significant increases in
      heart rate and minute ventilation occurred secondary to stimulation of the
      adrenergic nervous system.

PMID- 25856681
TI  - Pain Response after Maximal Aerobic Exercise in Adolescents across Weight Status.
AB  - INTRODUCTION: Pain reports are greater with increasing weight status, and
      exercise can reduce pain perception. It is unknown, however, whether exercise can
      relieve pain in adolescents of varying weight status. The purpose of this study
      was to determine whether adolescents across weight status report pain relief
      after high-intensity aerobic exercise (exercise-induced hypoalgesia (EIH)).
      METHODS: Sixty-two adolescents (15.1 +/- 1.8 yr, 29 males) participated in the
      following three sessions: 1) pressure pain thresholds (PPT) before and after
      quiet rest, clinical pain (McGill Pain Questionnaire), and physical activity
      levels (self-report and ActiSleep Plus Monitors) were measured, 2) PPT were
      measured with a computerized algometer at the fourth finger's nailbed, middle
      deltoid muscle, and quadriceps muscle before and after maximal oxygen uptake test
      (VO2max Bruce Treadmill Protocol), and 3) body composition was measured with dual
      energy x-ray absorptiometry. RESULTS: All adolescents met criteria for VO2max. On
      the basis of body mass index z-score, adolescents were categorized as having
      normal weight (n = 33) or being overweight/obese (n = 29). PPT increased after
      exercise (EIH) and were unchanged with quiet rest (trial * session, P = 0.02).
      EIH was similar across the three sites and between normal-weight and
      overweight/obese adolescents. Physical activity and clinical pain were not
      correlated with EIH. Overweight/obese adolescents had similar absolute VO2max
      (L.min(-1)) but lower relative VO2max (mL.kg(-1).min(-1)) compared with normal
      weight adolescents. When adolescents were categorized using FitnessGram standards
      as unfit (n = 15) and fit (n = 46), the EIH response was similar between fitness
      levels. CONCLUSIONS: This study is the first to establish that both overweight
      and normal-weight adolescents experience EIH. EIH after high-intensity aerobic
      exercise was robust in adolescents regardless of weight status and not influenced
      by physical fitness.

PMID- 25856684
TI  - Inhibition of viral protein translation by indomethacin in vesicular stomatitis
      virus infection: role of eIF2alpha kinase PKR.
AB  - Indomethacin, a cyclooxygenase-1 and -2 inhibitor widely used in the clinic for
      its potent anti-inflammatory/analgesic properties, possesses antiviral activity
      against several viral pathogens; however, the mechanism of antiviral action
      remains elusive. We have recently shown that indomethacin activates the double
      stranded RNA (dsRNA)-dependent protein kinase R (PKR) in human colon cancer
      cells. Because of the important role of PKR in the cellular defence response
      against viral infection, herein we investigated the effect of indomethacin on PKR
      activity during infection with the prototype rhabdovirus vesicular stomatitis
      virus. Indomethacin was found to activate PKR in an interferon- and dsRNA
      independent manner, causing rapid (< 5 min) phosphorylation of eukaryotic
      initiation factor-2 alpha-subunit (eIF2alpha). These events resulted in shutting
      off viral protein translation and blocking viral replication (IC50  = 2 MUM)
      while protecting host cells from virus-induced damage. Indomethacin did not
      affect eIF2alpha kinases PKR-like endoplasmic reticulum-resident protein kinase
      (PERK) and general control non-derepressible-2 (GCN2) kinase, and was unable to
      trigger eIF2alpha phosphorylation in the presence of PKR inhibitor 2-aminopurine.
      In addition, small-interfering RNA-mediated PKR gene silencing dampened the
      antiviral effect in indomethacin-treated cells. The results identify PKR as a
      critical target for the antiviral activity of indomethacin and indicate that
      eIF2alpha phosphorylation could be a key element in the broad spectrum antiviral
      activity of the drug. 

PMID- 25856683
TI  - ent-Kaurane Diterpenoids from Chinese Liverworts and Their Antitumor Activities
      through Michael Addition As Detected in Situ by a Fluorescence Probe.
AB  - It is generally accepted that the origin of the cytotoxicity of ent-kaurane
      diterpenoids is due to the formation of reactive oxygen species (ROS) and that
      the alpha,beta-unsaturated carbonyl is a pivotal moiety. Herein we demonstrate
      the isolation of 32 new and 12 known ent-kaurane diterpenoids from two Chinese
      liverworts. These compounds and three semisynthesized derivatives were screened
      against human cancer cell lines. The results revealed that their anticancer
      activities are caused by ROS formation through Michael modification of the
      protein thiols and depletion of glutathione unselectively. We also found that N
      acetylcysteine reverses the cytotoxicity of these diterpenoids by forming Michael
      adducts, not through a well-recognized ROS scavenging pathway as previously
      reported. In situ intracellular thiol detection helped us visualize the
      intracellular distribution of the diterpenoids and determine the potency of their
      cytotoxicity. An alkaline analogue was found to be more selective because of the
      altered subcellular distribution. 

PMID- 25856685
TI  - A Hybrid of Metabolic Flux Analysis and Bayesian Factor Modeling for Multiomic
      Temporal Pathway Activation.
AB  - The growing availability of multiomic data provides a highly comprehensive view
      of cellular processes at the levels of mRNA, proteins, metabolites, and reaction
      fluxes. However, due to probabilistic interactions between components depending
      on the environment and on the time course, casual, sometimes rare interactions
      may cause important effects in the cellular physiology. To date, interactions at
      the pathway level cannot be measured directly, and methodologies to predict
      pathway cross-correlations from reaction fluxes are still missing. Here, we
      develop a multiomic approach of flux-balance analysis combined with Bayesian
      factor modeling with the aim of detecting pathway cross-correlations and
      predicting metabolic pathway activation profiles. Starting from gene expression
      profiles measured in various environmental conditions, we associate a flux rate
      profile with each condition. We then infer pathway cross-correlations and
      identify the degrees of pathway activation with respect to the conditions and
      time course using Bayesian factor modeling. We test our framework on the most
      recent metabolic reconstruction of Escherichia coli in both static and dynamic
      environments, thus predicting the functionality of particular groups of reactions
      and how it varies over time. In a dynamic environment, our method can be readily
      used to characterize the temporal progression of pathway activation in response
      to given stimuli. 

PMID- 25856686
TI  - Efficacy and safety of anticoagulation therapy with different doses of enoxaparin
      for portal vein thrombosis in cirrhotic patients with hepatitis B.
AB  - BACKGROUND: Patients with cirrhosis have a high incidence of portal vein
      thrombosis (PVT), and optimal management of PVT in cirrhotic patients remains
      unclear. Currently, there is no paper on optimal doses of enoxaparin for the
      management of PVT with cirrhosis. AIMS: To evaluate the efficacy and safety of
      anticoagulation therapy with different doses of enoxaparin for PVT in cirrhotic
      patients with hepatitis B. MATERIALS AND METHODS: Sixty-five patients with
      hepatitis B-related cirrhosis and acute PVT were treated by different doses of
      enoxaparin. All the patients were assigned randomly to two groups: one group
      received enoxaparin 1 mg/kg subcutaneously every 12 h and the other group
      received enoxaparin 1.5 mg/kg subcutaneously every 24 h. Clinical, biochemical
      evaluation, Doppler ultrasound, and contrast-enhanced computed tomography were
      performed during the anticoagulation treatment. RESULTS: Of the 65 patients, 51
      patients (78.5%) achieved complete/partial recanalization of PVT after 6 months
      of anticoagulation therapy. Child-Pugh scores were lower in the 51 patients who
      achieved complete/partial recanalization than those of the 14 nonresponders
      (P<0.01). No patients showed variceal bleeding during anticoagulation therapy in
      the two groups. The rates of nonvariceal bleeding with the use of 1.5 mg/kg every
      24 h (23.5%) were higher than those with the use of 1 mg/kg every 12 h (6.4%).
      CONCLUSION: Anticoagulation therapy with different doses of enoxaparin for PVT in
      hepatitis B patients with cirrhosis is efficient and safe, and 1 mg/kg enoxaparin
      subcutaneously every 12 h is a better anticoagulation regimen in the treatment of
      PVT in cirrhotic patients.

PMID- 25856687
TI  - Oral health in patients with liver cirrhosis.
AB  - OBJECTIVE: The aim of this study was to describe the oral care habits and self
      perceived oral health in patients with liver cirrhosis, as well as to evaluate
      the impact of oral health on well-being and the relation to nutritional status.
      PARTICIPANTS AND METHODS: From October 2012 to May 2013, we carried out a
      prospective study on patients with liver cirrhosis. Questions on oral care habits
      and self-perceived oral health were answered, and the Oral Health Impact Profile
      questionnaire (OHIP-14) provided information on oral conditions. The findings
      were compared with The Danish Institute for Health Services Research report on
      the Danish population's dental status. RESULTS: One hundred and seven patients
      participated. Their oral care habits and self-perceived oral health were poorer
      than the Danish population; the patients had fewer teeth (on average 19 vs. 26, P
      = 0.0001), attended the dentist less frequently (P = 0.001), more rarely brushed
      teeth (P = 0.001) and had problems with oral dryness (68 vs. 14%, P = 0.0001).
      The patients' mean OHIP score was 5.21 +/- 7.2, with the most commonly reported
      problems being related to taste and food intake. An association was observed
      between the OHIP score and the patients' nutritional risk score (P = 0.01).
      CONCLUSION: Our results showed that cirrhosis patients cared less for oral health
      than the background population. Their resulting problems may be contributing
      factors to their nutritional risk and decreased well-being. Oral health problems
      may thus have adverse prognostic importance. Our results emphasize the need for
      measures to protect and improve the oral health of cirrhosis patients.

PMID- 25856688
TI  - Colorectal cancer in a second round after a negative faecal immunochemical test.
AB  - OBJECTIVE: The faecal immunochemical test is one of the tests recommended by
      scientific societies for colorectal cancer (CRC) screening in average-risk
      populations. Our aim was to evaluate the characteristics of CRC detected in a
      second round of screening after negative results in a first round. METHODS: We
      studied patients in whom CRC was detected in a screening programme. This
      programme included asymptomatic individuals between 50 and 69 years old and
      offered tests every 2 years. A total of 363,792 individuals were invited to
      participate in the first round of faecal immunochemical test screening and
      100,135 individuals in the second round after a first negative result. The
      screening strategy consisted of faecal testing of a single sample using an
      automated semiquantitative kit, with a cut-off of 20 MUg haemoglobin (Hb)/g
      faeces. RESULTS: The rate of positive results was 6.9% (16,467/238,647) in the
      first round and 4.8% (3359/69,193) in the second round (P < 0.0005). Overall, 860
      (0.36%) cases of CRC were detected in the first round and 100 (0.14%) in the
      second round (P < 0.005). The location of the cancer was proximal in 12.5 and 24%
      of cases detected in the first and second rounds, respectively (P = 0.008). Hb
      concentrations were higher in the first round (211 vs. 109 MUg Hb/g faeces in the
      second round; P = 0.002). Multivariate analysis confirmed that, in the second
      round, CRC diagnosed was more often proximal (hazard ratio vs. first round, 2.4;
      95% confidence interval, 1.3-4.4; P = 0.003) and the concentration of Hb/g faeces
      was lower (hazard ratio vs. first round, 2.1; 95% confidence interval, 1.3-3.5; P
      = 0.003). CONCLUSION: The CRC detection rate is lower in the second round of
      screening. Further, in the second round, CRC detected is more often in a proximal
      location and Hb concentrations are lower.

PMID- 25856689
TI  - Factors influencing acute infusion reactions in inflammatory bowel disease
      patients treated with infliximab in the era of scheduled maintenance therapy.
AB  - BACKGROUND: An acute infusion reaction during infliximab infusions could lead to
      drug withdrawal and limit the therapeutic armamentarium in inflammatory bowel
      diseases. AIM: To determine the risk and protective factors of an acute infusion
      reaction. MATERIALS AND METHODS: Data were retrieved retrospectively from
      electronic charts of patients from the 'Clermont-Ferrand IBD cohort'. RESULTS:
      Among 80 patients, including 51 (63.8%) patients with Crohn's disease, 23 (28.8%)
      experienced an acute infusion reaction. In multivariate analysis, the Crohn's
      disease nonstricturing nonfistulizing phenotype predicted an acute infusion
      reaction (odds ratio=11.40, 95% confidence interval 1.5-87.6; P=0.019).Among 1107
      infusions, we observed 38 acute infusion reactions (3.4%). In multivariate
      analysis, only resumption of infliximab after drug holiday was a major risk
      factor (odds ratio=24.87, 95% confidence interval 4.4-140.0; P<0.001).
      Concomitant premedication or immunosuppressant therapies did not prevent an acute
      infusion reaction.The patients who experienced an acute infusion reaction had a
      trend toward a higher rate of infliximab discontinuation (69.6 vs. 50.9%,
      P=0.14). CONCLUSION: An acute infusion reaction is a major event in the history
      of inflammatory bowel diseases patients treated with infliximab as it could lead
      to drug discontinuation and thus limits the therapeutic armamentarium
      considerably. The resumption of infliximab after drug holiday is a major risk
      factor for an acute infusion reaction. Premedication efficacy remains
      questionable and should be limited to these high-risk patients.

PMID- 25856690
TI  - Asbestos fibers in the gallbladder of patients affected by benign biliary tract
      diseases.
AB  - PURPOSE: This exploratory study aimed to evaluate the presence of asbestos fibers
      in the biliary tract of patients living in an asbestos-polluted area using
      scanning electron microscopy. METHODS: Thin gallbladder sections were obtained
      from five patients who were operated on for gallbladder stones and the bile fluid
      of one of the patients was analyzed using variable-pressure scanning electron
      microscopy coupled with energy-dispersive spectroscopy. All patients were from
      Casale Monferrato, Italy, a well-known asbestos-polluted city, where the Eternit
      factory had operated since the beginning of the century until 1985. RESULTS: All
      the inorganic phases found in the gallbladder were analyzed for morphology and
      chemistry. Fibers and particles consistent with minerals defined by law as
      'asbestos' were detected in three out of five patients. CONCLUSION: These
      findings suggest that asbestos fibers can be found in the gallbladder of patients
      exposed to asbestos, although how they reach the biliary tract remains unknown.
      Further studies to confirm these results are under way.

PMID- 25856691
TI  - The role of circulating microRNAs as novel biomarkers in diagnosing colorectal
      cancer: a meta-analysis.
AB  - OBJECTIVES: Several microRNAs (miRNAs) have been identified as potential
      circulating biomarkers in a number of different cancers including colorectal
      cancer (CRC). This study aims to assess the diagnostic performance of circulating
      miRNAs in detecting CRC through meta-analysis of all eligible relevant studies.
      MATERIALS AND METHODS: An extensive literature search was performed and studies
      that estimated the diagnostic accuracy of miRNAs in CRC were identified. Data
      from the eligible studies were collected and pooled; sensitivity, specificity,
      positive and negative likelihood ratios, diagnostic odds ratios, weighted
      symmetric summary ROC curve and the area under the curve (AUC) were calculated.
      Heterogeneity was evaluated using the Q-test and I(2)-statistics. In addition,
      subgroup analyses and meta-regression analyses were carried out to explore the
      potential sources of significant heterogeneity. RESULTS: A total of 16 studies
      were included in the meta-analysis according to the inclusion criteria. The
      overall analysis showed that circulating miRNAs have a relatively good diagnostic
      performance in CRC, with a sensitivity of 78%, a specificity of 79% and an AUC of
      0.87. Subgroup analyses showed that a single miRNA-21 test, as opposed to a panel
      miRNAs test, significantly improved the diagnostic accuracy with 83.4%
      sensitivity, 91.6% specificity, and AUC increasing to 0.94. CONCLUSION:
      Circulating miRNAs, especially miRNA-21, are promising diagnostic biomarkers in
      CRC. However, more prospective studies are required to further explore their
      diagnostic role and their usefulness in clinical practice.

PMID- 25856692
TI  - The degree of mucosal damage to the small intestine and serum immunoglobulin G4
      levels correlate with celiac disease.
AB  - BACKGROUND: Celiac disease (CD) is an immune-mediated and chronic inflammatory
      enteropathy, triggered by the ingestion of gluten in genetically susceptible
      individuals. Immunoglobulin G4 (IgG4)-related diseases are a recently defined
      emerging clinical condition, characterized by increased serum IgG4
      concentrations. The aim of this study was to investigate whether IgG4 levels
      correlate with the titers of intestinal antibodies and the degree of mucosal
      damage in CD patients. MATERIALS AND METHODS: A total of 41 CD patients and 28
      healthy controls were included in the study. All patients underwent a duodenal
      biopsy and were then diagnosed with the modified Marsh classification. Blood
      samples were obtained for IgG4 measurements. Serums were kept at -80  degrees C
      until the analysis was carried out and plasma IgG4 levels were determined using
      an enzyme-linked immune sorbent assay method with a diagnostic cutoff value of
      135 mg/dl. RESULTS: The mean age of the CD and the control group was 26.8 +/- 8.3
      and 26.9 +/- 6.2 years, respectively. The mean IgG4 levels were significantly
      higher in CD patients (283.21 +/- 39.02 mg/dl) compared with the healthy control
      group (68.97 +/- 15.89 mg/dl, P<0.0001). In the CD group, 27/41 patients and in
      the control group, 4/28 patients had high IgG4 levels (>135 mg/dl, P < 0.0001). A
      close correlation was found between the grade of mucosal damage, IgG4 levels, and
      antigliadin-IgA; the higher the grade Marsh score, the higher the measured IgG4
      (P < 0.05). CONCLUSION: In our study, IgG4 levels of CD patients were higher than
      normal ranges whereas the results of the control group were within physiologic
      limits. We also showed for the first time that there was a correlation between
      IgG4 levels, autoantibody, and severity of mucosal damage. To the best of our
      knowledge, this is the first study to evaluate IgG4 levels and mucosal damage in
      CD patients.

PMID- 25856693
TI  - Synthesis and reactivity of cyclometalated triamidophosphine complexes of niobium
      and tantalum.
AB  - The triamidophosphine protioligand 1 reacts with the homoleptic
      pentakis(dimethylamido) precursors of niobium and tantalum [M(NMe2)5, where M =
      Nb, Ta] to form cyclometalated complexes of the type [N2PCN-kappa(5)
      N,N,P,C,N]M(NMe2) (2-M). Apart from the three amido donors, one benzylic position
      of the ligand backbone is deprotonated over the course of this reaction,
      resulting in the formation of a new M-C bond. As a consequence, a metallaziridine
      substructure is formed, and the triamidophosphine moiety thus serves as a
      tetraanionic pentadentate ligand. The dimethylamido complexes 2-M can be
      converted into the corresponding triflates [N2PCN-kappa(5)-N,N,P,C,N]M(OTf) (3-M)
      and alkyl complexes [N2PCN-kappa(5)-N,N,P,C,N]M(CH2SiMe3) (4-M) by treatment with
      triethylsilyl triflate (Et3SiO3SCF3) followed by (trimethylsilyl)methyllithium
      (LiCH2SiMe3). The alkyl complexes exhibit interesting reactivities, including a
      second cyclometalative backbone activation affording the trimethylphosphine
      stabilized complexes [NP(CN)2-kappa(6)-N,P,C,N,C,N]M(PMe3) (5-M). In the case of
      tantalum, the formation of a dinuclear hydrido complex (6) is observed upon
      hydrogenation of 4-Ta. In the case of niobium, the metallaziridine substructure
      in 4-Nb is prone to ring opening via protonation with triphenylsilylamine
      (Ph3SiNH2), resulting in formation of the corresponding imido complex [PN3
      kappa(4)-P,N,N,N]Nb=NSiPh3 (7).

PMID- 25856694
TI  - The fate of the triplet excitations in the Fenna-Matthews-Olson complex.
AB  - The fate of triplet excited states in the Fenna-Matthew-Olson (FMO) pigment
      protein complex is studied by means of time-resolved nanosecond spectroscopy and
      exciton model simulations. Experiments reveal microsecond triplet excited-state
      energy transfer between the bacteriochlorophyll (BChl) pigments, but show no
      evidence of triplet energy transfer to molecular oxygen, which is known to
      produce highly reactive singlet oxygen and is the leading cause of photo damage
      in photosynthetic proteins. The FMO complex is exceptionally photo stable despite
      the fact it contains no carotenoids, which could effectively quench triplet
      excited states of (bacterio)chlorophylls and are usually found within pigment
      protein complexes. It is inferred that the triplet excitation is transferred to
      the lowest energy pigment, BChl 3, within the FMO complex, whose triplet state
      energy is shifted by pigment-protein interactions below that of the singlet
      oxygen excitation. Thus, the energy transfer to molecular oxygen is blocked and
      the FMO does not need carotenoids for photo protection. 

PMID- 25856695
TI  - Memory restorative ability of clioquinol in copper-cholesterol-induced
      experimental dementia in mice.
AB  - CONTEXT: Results from various studies indicate that the presence of certain heavy
      metals such as aluminum (Al), arsenic (As), copper (Cu), lead (Pb), and mercury
      (Hg) may enhance the aggregation of Abeta and oxidative stress levels leading to
      neuronal toxicity and Alzheimer's disease (AD). Studies also reveal that
      anomalous brain copper-cholesterol (Cu-Ch) homeostasis may lead to memory
      deficits in Swiss albino mice. OBJECTIVE: The present study investigates the anti
      amnesic potential of clioquinol (5-chloro-7-iodoquinolin-8-ol) in cognitive
      deficits associated with experimental dementia induced by Cu-Ch. MATERIALS AND
      METHODS: Administration of Cu-Ch {0.21 mg/kg, per os - 2% w/v, per os for 8
      weeks} was used to induce dementia in Swiss albino mice. The Morris water maze
      (MWM) test was performed to assess the effect on learning and memory. A battery
      of biochemical estimations was performed following the MWM test such as brain
      reduced glutathione (GSH), superoxide dismutase (SOD), thiobarbituric acid
      reactive species (TBARS), acetylcholinestrase (AChE) activity, and serum
      cholesterol levels. RESULTS: Administration of Cu-Ch produced a marked decline in
      MWM performance measured during the acquisition (78.9 +/- 3.3) and retrieval
      trials (9.5 +/- 2.4), reflecting impairment of learning and memory. Cu-Ch-treated
      mice also exhibited a marked accentuation of AChE activity (5.8 +/- 0.55) and
      TBARS levels (9.74 +/- 1.9) along with a decline in the GSH level (15.4 +/- 3.3)
      and the SOD level (26 +/- 2.5) when compared with the untreated control group.
      Administration of clioquinol significantly attenuated Cu-Ch-induced memory
      deficits and biochemical alterations. DISCUSSION AND CONCLUSION: The findings
      demonstrate memory restorative ability of clioquinol which may be attributed to
      its anti-cholinesterase, antioxidative, and cholesterol-lowering potential.

PMID- 25856696
TI  - Bioactive compounds and scavenging capacity of extracts from different parts of
      Vismia cauliflora against reactive oxygen and nitrogen species.
AB  - CONTEXT: Vismia cauliflora A.C.Sm. [Hypericaceae (Clusiaceae)] is a plant from
      Amazonian forest. It is used by Amerindians to treat dermatosis and inflammatory
      processes in the skin and has been considered an interesting source of bioactive
      compounds. OBJECTIVE: We evaluated the scavenging capacity of extracts from V.
      cauliflora (leaf, branch, stem bark, flower, and whole fruit) against reactive
      oxygen (ROS) and nitrogen species (RNS), namely, superoxide radical ([Formula:
      see text]), hydrogen peroxide (H2O2), hypochlorous acid (HOCl), singlet oxygen
      ((1)O2), nitric oxide ((*)NO), and peroxynitrite (ONOO(-)). In addition, for the
      first time, the profile of phenolic compounds and carotenoids was determined.
      MATERIALS AND METHODS: The scavenging capacities of each extract were determined
      using specific probes (fluorescent, colorimetric, and chemiluminescent) to detect
      different reactive species ((1)O2, HOCl, H2O2, [Formula: see text], (*)NO, and
      ONOO(-)). The identification and the quantification of phenolic compounds and
      carotenoids were carried out by HPLC-DAD-ESI-MS/MS and HPLC-DAD, respectively.
      RESULTS: (-)-Epicatechin and proanthocyanidin dimers and trimer were the major
      phenolic compounds tentatively identified in leaf, branch, stem bark, and flower
      extracts, while dihydroxybenzoic acids were the major compounds in whole fruit
      extracts. All-trans-zeinoxanthin and all-trans-beta-carotene were the major
      carotenoids tentatively identified in leaf extracts. All extracts of V.
      cauliflora showed high efficiency against all tested ROS and RNS, although flower
      and stem bark extracts exhibited the most remarkable scavenging capacity,
      especially for (*)NO and ONOO(-). DISCUSSION AND CONCLUSION: Vismia cauliflora
      has great potential to be used in the development of phytopharmaceutical products
      due to its characteristic of being a promising source of bioactive compounds with
      high antioxidant properties.

PMID- 25856697
TI  - Free radical scavenging actions of three Trifolium species in the protection of
      blood plasma antioxidant capacity in vitro.
AB  - CONTEXT: Three clover [Trifolium L. (Leguminosae)] species were selected on the
      basis of data from traditional medicine, phytochemical profiles, and agricultural
      significance. OBJECTIVE: The in vitro evaluations of free radical scavenging
      properties, ferric reducing abilities, and antioxidant effects of extracts from
      T. pratense L. (crude extract and phenolic fraction), T. pallidum L., and T.
      scabrum L. (phenolic fractions) were performed. MATERIALS AND METHODS: Activities
      of the Trifolium extracts were determined at their final concentrations of 1.5-50
      ug/ml. Free radical scavenging properties of methanol extract solutions were
      estimated by the reduction of DPPH(*) and ABTS(*) radicals. Measurements of the
      total antioxidant capacity (TAC) were carried out to assess the antioxidant
      activities of the extracts in human blood plasma under conditions of oxidative
      stress, induced by 200 MUM peroxynitrite. RESULTS: The phenolic fraction of T.
      pratense displayed the strongest ABTS(*) and DPPH(*) radical scavenging effects
      (EC50 value of 21.69 and 12.27 ug/ml, respectively). The EC50 value for T.
      pallidum extract attained 29.77 and 30.06 ug/ml. The two remaining extracts were
      less potent scavengers (EC50 value higher than 50 ug/ml). Similar differences
      were obtained during evaluation of the ferric reducing abilities. Analysis of
      antioxidant properties of the extracts in blood plasma did not provide such
      evident differences in their actions, however, it indicated that the T. pratense
      phenolic fraction displayed the strongest effect. CONCLUSIONS: The examined
      Trifolium extracts partly protected blood plasma and enhanced its non-enzymatic
      antioxidant defense against harmful action of peroxynitrite in vitro.

PMID- 25856698
TI  - Content of phenolic compounds in wild populations of Epilobium angustifolium
      growing at different altitudes.
AB  - CONTEXT: Flavonoids are regarded as essential ingredients for the anti
      inflammatory activity of Epilobium angustifolium L. (Onagraceae). The metabolic
      profiles of medicinal plants vary aside from genetic determination due to the
      influence by external factors. OBJECTIVES: This study evaluates the influence of
      altitudinal variation on the content of flavonoids in E. angustifolium in two
      consecutive growing periods. MATERIALS AND METHODS: Aerial and herbaceous plant
      materials were collected at three different altitudes (800, 1000, and 1500 m)
      during two collection periods. Plant samples (11-13 samples per altitude and
      year) were extracted with methanol using accelerated solvent extraction (ASE).
      Identification and quantification of the constituents were achieved by
      chromatographic means of HPLC-PDA and LC-PDA-MS analyses. RESULTS: Rising
      concentrations of flavonol 3-O-glycosides could be detected with increasing
      altitude. The content of the major compound, quercetin 3-O-glucuronide, ranged
      from 4.4 +/- 2.05 (800 m) to 4.9 +/- 1.03 (1000 m) and up to 6.6 +/- 1.14 mg/g
      (1500 m). The total amount of flavonol 3-O-glycosides in 73 analyzed samples
      ranged from 10.7 +/- 1.37 up to 17.3 +/- 1.99 mg/g. DISCUSSION: Quercetin-3-O
      glucuronide can be considered as a potential marker for the increased production
      of flavonols in herbal parts of E. angustifolium at higher altitudinal levels.
      CONCLUSION: The study confirms that environmental factors at higher altitude
      result in elevated levels of flavonols in aerial plant tissues of E.
      angustifolium. Specific factors for influencing the flavonoid content have to be
      clarified in further studies.

PMID- 25856699
TI  - Tectorigenin regulates adipogenic differentiation and adipocytokines secretion
      via PPARgamma and IKK/NF-kappaB signaling.
AB  - CONTEXT: Obesity is associated with a number of diseases with metabolic
      abnormalities such as type 2 diabetes (T2D). OBJECTIVE: We investigate the
      effects of tectorigenin on 3T3-L1 preadipocyte differentiation and adipocytokines
      secretion. MATERIALS AND METHODS: The effects of tectorigenin on adipocyte
      differentiation were studied using Oil Red O staining. Effects of tectorigenin on
      adipogenesis-related genes expression and adipocytokines secretion were measured
      by the real-time quantitative RT-PCR and ELISA method, respectively. Reporter
      gene assays were performed to determine the PPARgamma and NF-kappaB
      transactivation. We also used [(3)H]-2-deoxy-d-glucose to study the glucose
      uptake, and the IKK/NF-kappaB signaling pathway was assessed by western blot
      analysis. HFD/STZ rats were used to evaluate the therapeutic efficacies of
      tectorigenin. RESULTS: Tectorigenin 10, 25, 50, and 75 MUM inhibited 3T3-L1
      adipogenesis and related genes transcription. TNF-alpha-induced changes of IL-6,
      MCP-1, as well as adiponectin in 3T3-L1 were markedly reversed by tectorigenin at
      75 MUM. Further investigation using reporter gene revealed that tectorigenin was
      a partial PPARgamma agonist with an IC50 value of 13.3 MUM. Tectorigenin improved
      basal and insulin-stimulated glucose uptake in mature 3T3-L1 adipocytes.
      Moreover, tectorigenin antagonized TNF-alpha-induced NF-kappaB transactivation
      and p65 nuclear translocation. Although tectorigenin (50 and 100 mg/kg) displayed
      the ability to promote insulin sensitivity and improve glucose metabolism in
      HFD/STZ rats, it did not cause significant side effects such as body weight gain,
      fluid retention, or cardiac hypertrophy. DISCUSSION AND CONCLUSION: These results
      suggest that tectorigenin may ameliorate hyperglycemia by blocking preadipocyte
      differentiation and adipocytokines secretion in which PPARgamma and NF-kappaB
      signaling pathways were involved.

PMID- 25856700
TI  - Antipsychotic activity of standardized Bacopa extract against ketamine-induced
      experimental psychosis in mice: Evidence for the involvement of dopaminergic,
      serotonergic, and cholinergic systems.
AB  - CONTEXT: Schizophrenia is a chronic disabling psychiatric disorder affecting 1%
      of the population worldwide. Due to the adverse effects of available
      antipsychotic medications, recent investigations have focused on the search for
      well-tolerated, safe molecules from natural resources to control the severity and
      progression of schizophrenia. OBJECTIVE: To screen the standardized extract of
      Bacopa monniera Linn. (Scrophulariaceae) (BM) for its antipsychotic potential in
      the ketamine-induced psychosis model with mice. MATERIALS AND METHODS: Graded
      dose of BM (40, 80, and 120 mg/kg, p.o.) were given to the mice 1 h prior to
      ketamine administration and tested for positive symptoms and cognitive deficits.
      A chronic ketamine treatment regimen was used to study the effect of BM on
      negative symptoms such as immobility enhancement. Each mouse was used once for
      the behavioral studies. RESULTS: BM reduced ketamine-induced hyperactivity with
      an EC50 value of 76.60 mg/kg. The 80 mg/kg dose was used for all other behavior
      analysis. Pretreatment with BM at 80 mg/kg showed two-fold increases in transfer
      latency time (TLT) in passive avoidance task. Chronic BM pretreatment (80 mg/kg
      p.o. daily * 10 d) ameliorated the ketamine-induced enhanced immobility effect by
      21% in the forced swim test. BM treatment reversed ketamine-induced increase in
      monoamine oxidase activity in both cortex and striatum and normalized the
      acetylcholinesterase activity and the glutamate levels in the hippocampus.
      DISCUSSION AND CONCLUSION: Overall our findings suggest that BM possesses
      antipsychotic properties which might be due to its modulatory action on dopamine,
      serotonin, and glutamate neurotransmission.

PMID- 25856701
TI  - Assessment of in vitro antipsoriatic activity of selected Indian medicinal
      plants.
AB  - CONTEXT: Phyllanthus simplex Retz. (Phyllanthaceae), Crotolaria juncea Linn.
      (Leguminosae), Leucas aspera Linn. (Lamiaceae), and Vitex glabrata R.Br.
      (Verbenaceae) are well-known Indian medicinal plants. Different parts of these
      plants are used for healing purposes traditionally in the treatment of psoriasis
      and various other disorders. This prompted us to assess the antipsoriatic
      activities of these plants. OBJECTIVES: Petroleum ether and ethanol extracts of
      the selected plants, i.e., P. simplex (whole plant), C. juncea (seeds), L. aspera
      (aerial parts), and V. glabrata (leaves) were investigated for their in vitro
      antipsoriatic activity. MATERIALS AND METHODS: Antipsoriatic activity of the
      extracts was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide (MTT) assay, using HaCaT cells. About 200 ul of different concentrations
      (25, 50, 100, 200, and 400 ug/ml) of test samples were prepared in the cell
      culture medium and incubated for 24 h before MTT assay to determine the viable
      cells. The effect of these extracts on nitric oxide (NO) production and lipid
      peroxidation was also evaluated. RESULTS: Our findings revealed that these plants
      showed promising skin keratinocyte antiproliferative activity. However, the
      petroleum ether extract of C. juncea (CJPE) and ethanol extract of L. aspera
      (LAEE) were found to exhibit significant activity (IC50 value = 45.45 and 55.36
      ug/ml, respectively). DISCUSSION AND CONCLUSIONS: The inhibitory action against
      NO production and lipid peroxidation in HaCaT cells suggested that the
      antipsoriatic activity of the extracts was mediated by an antioxidant mechanism.
      These findings validate the claims of the use of these plants in the treatment of
      psoriasis.

PMID- 25856702
TI  - Vitamin D in cancer chemoprevention.
AB  - CONTEXT: There is increasing evidence that Vitamin D (Vit D) and its metabolites,
      besides their well-known calcium-related functions, may also exert
      antiproliferative, pro-differentiating, and immune modulatory effects on tumor
      cells in vitro and may also delay tumor growth in vivo. OBJECTIVE: The aim of
      this review is to provide fresh insight into the most recent advances on the role
      of Vit D and its analogues as chemopreventive drugs in cancer therapy. METHODS: A
      systematic review of experimental and clinical studies on Vit D and cancer was
      undertaken by using the major electronic health database including ISI Web of
      Science, Medline, PubMed, Scopus and Google Scholar. RESULTS AND CONCLUSION:
      Experimental and clinical observations suggest that Vit D and its analogues may
      be effective in preventing the malignant transformation and/or the progression of
      various types of human tumors including breast cancer, prostate cancer,
      colorectal cancer, and some hematological malignances. These findings suggest the
      possibility of the clinical use of these molecules as novel potential
      chemopreventive and anticancer agents.

PMID- 25856703
TI  - The anti-hyperalgesic and anti-inflammatory profiles of p-cymene: Evidence for
      the involvement of opioid system and cytokines.
AB  - CONTEXT: Pain corresponds to the most frequent reason for visits to physicians,
      and its control by conventional drugs is accompanied by several side effects,
      making treatment difficult. For this reason, new chemical entities derived from
      natural products still hold great promise for the future of drug discovery to
      pain treatment. OBJECTIVE: The objective of this study was to evaluate the
      antinociceptive and anti-inflammatory profiles of p-cymene (PC), a monocyclic
      monoterpene, and its possible mechanisms of action. MATERIALS AND METHODS: Mice
      treated acutely with PC (25, 50, or 100 mg/kg, i.p.) were screened for
      carrageenan-induced hyperalgesia and the inflammatory components of its cascade
      (30-180 min), carrageenan-induced pleurisy (4 h), and tail-flick test (1-8 h).
      Also, we observed the PC effect on the generation of nitric oxide by macrophages
      and the activation of neurons in the periaqueductal gray (PAG) by
      immunofluorescence. RESULTS: PC reduced (p < 0.001) the hyperalgesia induced by
      carrageenan, TNF-alpha, dopamine, and PGE2. PC decrease total leukocyte migration
      (100 mg/kg: p < 0.01), neutrophils (50 and 100 mg/kg: p < 0.05 and 0.001), and
      TNF-alpha (25, 50, and 100 mg/kg: p < 0.01, 0.05, and 0.001, respectively),
      besides reducing NO production (p < 0.05) in vitro. PC produced antinociceptive
      effect in tail-flick test (p < 0.05), which was antagonized by naloxone,
      naltrindole, nor-BNI, and CTOP, and increased (p < 0.001) the number of c-Fos
      immunoreactive neurons in PAG. DISCUSSION AND CONCLUSION: These results provide
      information about the anti-hyperalgesic and anti-inflammatory properties of PC
      suggesting a possible involvement of the opioid system and modulating some pro
      inflammatory cytokines.

PMID- 25856704
TI  - Antimicrobial resistance and virulence-related genes of Streptococcus obtained
      from dairy cows with mastitis in Inner Mongolia, China.
AB  - CONTEXT: Mastitis is the most expensive disease in the dairy cattle industry and
      results in decreased reproductive performance. Streptococcus, especially
      Streptococcus agalactiae, possesses a variety of virulence factors that
      contribute to pathogenicity. OBJECTIVE: Streptococcus isolated from mastitis was
      tested to assess the prevalence of antimicrobial resistance and distribution of
      antibiotic resistance- and virulence-related genes. MATERIALS AND METHODS: Eighty
      one Streptococcus isolates were phenotypically characterized for antimicrobial
      resistance against 15 antibiotics by determining minimum inhibitory
      concentrations (MIC) using a micro-dilution method. Resistance- and virulence
      related genes were detected by PCR. RESULTS: High percentage of resistance to
      beta-lactams, along with tetracycline and erythromycin, was found. Resistance to
      three or more of seven antimicrobial agents was observed at 88.9%, with
      penicillin-tetracycline-erythromycin-clindamycin as the major profile in
      Streptococcus isolates. Resistant genes were detected by PCR, the result showed
      that 86.4, 86.4, 81.5, and 38.3% of isolates were mainly carrying the pbp2b,
      tetL, tetM, and ermB genes, respectively. Nine virulence genes were investigated.
      Genes cyl, glnA, cfb, hylB, and scaA were found to be in 50% of isolates, while
      3.7, 21, and 4.9% of isolates were positive for bca, lmb, and scpB, genes,
      respectively. None of the isolates carried the bac gene. DISCUSSION AND
      CONCLUSION: This study suggests the need for prudent use of antimicrobial agents
      in veterinary clinical medicine to avoid the increase and dissemination of
      antimicrobial resistance arising from the use of antimicrobial drugs in animals.

PMID- 25856706
TI  - The antinociceptive effects of magnesium sulfate and MK-801 in visceral
      inflammatory pain model: The role of NO/cGMP/K(+)ATP pathway.
AB  - CONTEXT: Magnesium and MK-801 (dizocilpine), antagonists of N-methyl-d-aspartate
      receptors, are involved in the processing of pain. OBJECTIVE: This study
      determines whether magnesium sulfate (MS) and MK-801 affects visceral
      inflammatory pain and determines a possible mechanism of action. MATERIALS AND
      METHODS: Analgesic activity was assessed using the acetic acid-induced writhing
      test in rats. MS (1-45 mg/kg) or MK-801 (0.005-0.03 mg/kg) was administrated
      subcutaneously (s.c.). To assess possible mechanisms of action, we examined the
      effects of l-NAME (10 mg/kg, intraperitoneal), methylene blue (0.5 mg/kg, s.c.),
      and glibenclamide (3 mg/kg, s.c.) on the effect of MS or MK-801. RESULTS: MS and
      MK-801 showed biphasic and linear dose-response pattern, respectively. MS reduces
      the number of writhing on the dose of 1, 5, and 15 mg/kg by 60, 50, and 78%,
      respectively, while it has no effects on the doses of 30 and 45 mg/kg. MK-801
      (0.005-0.03 mg/kg) showed decrease in the number of writhing by 33-79%. The mean
      effective doses of MS and MK-801 were 6.6 (first phase) and 0.009 mg/kg,
      respectively. Both drugs did not impair the rotarod performance. l-NAME,
      methylene blue, and glybenclamide reduced the effect of MK-801 by 100, 43, and
      64%, respectively, but not the effect of MS. CONCLUSIONS: The results suggest
      that MS and MK-801 may be useful analgesics in the management of visceral
      inflammatory pain, at doses that do not induce motor impairment. The modulation
      of NO/cGMP/K+ATP pathway plays an important role in the antinociceptive mechanism
      of MK-801, but does not contribute to the antinociceptive effect of MS.

PMID- 25856705
TI  - Antioxidant and hepatoprotective activities of the oil fractions from wild carrot
      (Daucus carota ssp. carota).
AB  - CONTEXT: Wild carrot, Daucus carota L. ssp. carota (Apiacae), is widely
      distributed throughout the world and has various uses in traditional medicine in
      Lebanon. OBJECTIVE: The present study aimed to fractionate and analyze the
      chemical composition of the Daucus carota oil extract (DCOE) fractions and to
      evaluate their antioxidant and hepatoprotective properties in vitro and in vivo.
      MATERIALS AND METHODS: DCOE was chromatographed on silica gel column to produce
      four fractions: pentane (F1), 50:50 pentane:diethyl ether (F2), diethyl ether
      (F3), and 93:7 chloroform: methanol (F4). Qualitative and quantitative analyses
      of oil fractions were performed by GC-MS and HPLC techniques. The in vitro
      antioxidant properties were assessed using DPPH, FIC, and ferric-reducing
      antioxidant power (FRAP) assays. The hepatoprotective property was determined by
      examining the levels of serum markers (alanine transaminase (ALT) and aspartate
      transaminase (AST)) and hepatic antioxidant (superoxide dismutase (SOD), catalase
      (CAT), and glutathione-S-transferase (GST)) enzymes in CCl4-intoxicated mice
      pretreated with intraperitoenal 50, 100, or 200 mg/kg b.w. of the oil fractions
      for 5 d. RESULTS: GCMS analysis of F2 revealed the presence of 2-himachalen-6-ol
      (61.4%) which is reported for the first time in Daucus carota species. F3 and F4
      were rich in phenolics and flavonoids and demonstrated significant DPPH activity
      (IC50 = 0.29 and 0.38 mg/ml, respectively) and high FRAP values (225.11 and
      437.59 umol FeSO4/g, respectively). The sesquiterpene-rich fraction F1 had the
      highest FIC ability (IC50 = 0.28 mg/ml). Pretreatment with F1 and F4 reversed the
      CCl4-induced decrease in SOD, CAT, and GST levels and reduced significantly
      hepatic damage. DISCUSSION AND CONCLUSION: The current results suggested that
      wild carrot oil fractions exhibited a unique chemical composition and possessed
      significant antioxidant activities as well as hepatoprotective effects against
      CCl4-induced hepatotoxicity.

PMID- 25856707
TI  - Digitoflavone provokes mitochondrial biogenesis in PC12 cells: A protective
      approach to oxidative stress.
AB  - CONTEXT: Reactive oxygen species (ROS) are known to be one of the main causes of
      neurodegenerative disorders, and flavonoids play characteristic roles in a
      variety of biological activities, and specially are known to be antioxidant
      reagents. OBJECTIVE: In this study, we investigated neuroprotective effects of
      digitoflavone to suppress H2O2 -induced cell death in neuron-like PC12 cells.
      MATERIAL AND METHODS: PC12 cells were pre-treated with digitoflavone for 2 h and
      then cells were exposed to H2O2 for 18 h. The cells' viability was evaluated by
      MTT assay. Rhodamine 123 staining was used for the determination of mitochondrial
      membrane potential (DeltaPsim). The intracellular ROS aggregation was determined
      by using 2',7'-dichlorofluorescein diacetate. Also, the level of mitochondrial
      biogenesis factors was measured by western blot. The antioxidant capacity of
      digitoflavone was also determined by measuring reduced glutathione (GSH) level
      and catalase (CAT) activity quantification. RESULTS: Digitoflavone significantly
      elevated cells' viability at concentrations of 10 and 20 uM. Also, digitoflavone
      attenuated intracellular level of ROS, and stabilized DeltaPsim. Moreover,
      digitoflavone increased phosphorylation of AMP-activated protein kinase (AMPK)
      and, consequently, elevated mitochondrial biogenesis factors which were reduced
      after H2O2 exposure. We emphasized on the protective effect of digitoflavone
      through increasing mitochondrial biogenesis by specifically inhibiting AMPK.
      Antioxidant ability of digitoflavone was indicated by the elevation of GSH level
      and CAT activity. CONCLUSION: As a result, digitoflavone stabilize DeltaPsim,
      enhanced cell viability through inducing mitochondrial biogenesis pathway, and
      increased antioxidant capacity of the cells which lead to better combating the
      oxidative stress.

PMID- 25856708
TI  - Chemical composition and pharmacological properties of the essential oils
      obtained seasonally from Lippia thymoides.
AB  - CONTEXT: Lippia thymoides Mart. & Schauer (Verbenaceae) is used in folk medicine
      to treat wounds, fever, bronchitis, rheumatism, headaches, and weakness.
      OBJECTIVE: This study determinates the chemical composition of essential oils
      from L. thymoides, obtained at during each of the four seasons and correlates
      with pharmacological properties. MATERIALS AND METHODS: Essential oils were
      obtained by hydrodistillation and analyzed by gas chromatography coupled to mass
      spectroscopy (GC-MS). Antioxidant activity was determined by DPPH free radical
      scavenging and beta-carotene bleaching methods. The antimicrobial assays were
      performed by minimum inhibitory concentration (MIC) and minimum microbicidal
      concentration (MMC) methods. Isolated rat aorta and uterus, and guinea-pig
      trachea were utilized to evaluate relaxant potential in pre-contracted smooth
      muscle. RESULTS AND DISCUSSION: Essential oils from leaves of L. thymoides had
      the sesquiterpene beta-caryophyllene (17.22-26.27%) as the major constituent
      followed by borneol (4.45-7.36%), camphor (3.22-8.61%), camphene (2.64-5.66%),
      and germacrene D (4.72-6.18%). In vitro assays showed that these essential oils
      do not have antioxidant activity, have antimicrobial selectivity to Gram-positive
      bacteria Staphylococcus aureus (MIC = 0.004 mg/mL and MMC = 0.26-10.19 mg/mL) and
      Micrococcus luteus (MIC = 0.03 mg/mL and MMC = 8.43 mg/mL), relax isolated rat
      aorta (EC50 = 305-544 MUg/mL, with endothelium; and EC50 = 150-283 MUg/mL,
      without endothelium), and uterus (EC50 = 74-257 MUg/mL), and minor potency,
      isolated guinea-pig trachea. CONCLUSIONS: Lippia thymoides is a source of natural
      products of pharmaceutical interest, being necessary additional studies to
      determine the substances involved in the biological activities.

PMID- 25856710
TI  - Formation of harmful compounds in biotransformation of lilial by microorganisms
      isolated from human skin.
AB  - CONTEXT: The biotransformation of lilial results in an acid that is used in the
      dairy industry, in perfumery, as an intermediate in the manufacture of
      pharmaceuticals and cosmetics, and as a food additive for enhancing taste.
      OBJECTIVE: This study investigates the biotransformation of lilial by
      Staphylococcus aureus and Staphylococcus epidermidis, two bacterial species
      isolated from human skin. MATERIALS AND METHODS: Both species of Staphylococcus
      were isolated in samples taken from the skin of individuals living in a rural
      area of Iran. The pH of the culture medium was optimized, and after culturing the
      microorganisms, the bacteria were added to a flask containing a nutrient broth
      and incubated for several hours. The flasks of bacteria were combined with
      lilial, and various biochemical tests and diagnostics were performed, including
      Fourier transform infrared spectroscopy (FT-IR), ultraviolet-visible
      spectrophotometry (UV-Vis), and gas chromatography-mass spectroscopy (GC-MS).
      RESULTS: The S. aureus produced isobutyric acid (2-methylpropanoic acid) after 72
      h (71% of the total products yielded during biotransformation), whereas the S.
      epidermidis produced terpenoid alcoholic media after 24 h (90% of total products
      obtained). DISCUSSION AND CONCLUSION: The results obtained indicate that
      biotransformation of lilial by S. aureus is more desirable than by S. epidermidis
      due to the highly efficient production of a single product. Bourgeonal and liliol
      were two toxic compounds produced during biotransformation, which indicates that
      the use of lilial in cosmetics can be harmful to the skin.

PMID- 25856709
TI  - Effects of Piper nigrum extracts: Restorative perspectives of high-fat diet
      induced changes on lipid profile, body composition, and hormones in Sprague
      Dawley rats.
AB  - CONTEXT: Piper nigrum Linn (Piperaceae) (PnL) is used in traditional medicine to
      treat gastric ailments, dyslipidemia, diabetes, and hypertension. OBJECTIVE: The
      present study explores the possible protective effects of P. nigrum extracts on
      high-fat diet-induced obesity in rats. MATERIALS AND METHODS: High-fat diet
      induced obese rats were treated orally with 200 mg/kg bw of different extracts
      (hexane, ethylacetate, ethanol, and aqueous extracts) of PnL for 42 d. The
      effects of PnL extracts on body composition, insulin resistance, biochemical
      parameters, leptin, adiponectin, lipid profile, liver marker enzymes, and
      antioxidants were studied. RESULTS AND DISCUSSION: The HFD control group rats
      showed a substantial raise in body weight (472.8 +/- 9.3 g), fat% (20.8 +/-
      0.6%), and fat-free mass (165.9 +/- 2.4 g) when compared with normal control rats
      whose body weight, fat%, and fat-free mass were 314.3 +/- 4.4 g, 6.4 +/- 1.4%,
      and 133.8 +/- 2.2 g, respectively. Oral administration of ethyl acetate or
      aqueous extracts of PnL markedly reduced the body weight, fat%, and fat-free mass
      of HFD-fed rats. In contrast to the normal control group, a profound increase in
      plasma glucose, insulin resistance, lipid profile, leptin, thiobarbituric acid
      reactive substance (TBARS), and the activities of lipase and liver marker
      enzymes, and a decrease in adiponectin and antioxidant enzymes were noted in HFD
      control rats. Administration of PnL extracts to HFD-induced obese rats
      significantly (p < 0.05) restored the above profiles. CONCLUSION: PnL extracts
      significantly reduced the body weight, fat%, and ameliorated HFD-induced
      hyperlipidemia and its constituents.

PMID- 25856711
TI  - Chemical constituents of the Annona glabra fruit and their cytotoxic activity.
AB  - CONTEXT: Traditional Chinese medicines have attracted increasing interest as
      potential sources of novel drugs with a wide range of biological and
      pharmacological activities. Annona glabra Linn (Annonaceae) is used in
      traditional medicine as an anticancer drug. Phytochemical investigation of this
      plant led to the isolation of acetogenins, ent-kauranes, peptides, and alkaloids.
      In addition, compounds exhibited anticancer, anti-HIV-reserve, and antimalaria.
      OBJECTIVE: Isolation, structure determination, and cytotoxic activity evaluation
      of compounds from the methanol extract from A. glabra fruits. MATERIALS AND
      METHODS: Using chromatographic methods to isolate compounds from the A. glabra
      methanol extract. The cytotoxic activity of compounds was evaluated by a 3-[4,5
      dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. In addition,
      compounds which showed significant cytotoxic activity were chosen for further
      study apoptosis characteristics. RESULTS: One new, (2E,4E,1'R,3'S,5'R,6'S)
      dihydrophaseic acid 1,3'-di-O-beta-d-glucopyranoside, and eight known compounds,
      (2E,4E,1'R,3'S,5'R,6'S)-dihydrophaseic acid 3'-O-beta-d-glucopyranoside (2),
      icariside D2 (3), icariside D2 6'-O-beta-d-xylopyranoside (4), 3,4
      dimethoxyphenyl O-beta-d-glucopyranoside (5), 3,4-dihydroxybenzoic acid (6),
      blumenol A (7), cucumegastigmane I (8), and icariside B1 (9), were isolated from
      the fruits of A. glabra. Icariside D2 (3) was found to show significant cytotoxic
      activity on the HL-60 cell line with the IC50 value of 9.0 +/- 1.0 uM and did not
      show cytotoxic activity on the Hel-299 normal cell line. The further test
      indicated that compound 3 induced apoptosis via alteration of expression of
      apoptosis-related proteins and decreased phosphorylation of AKT in HL-60 cells.
      DISCUSSION AND CONCLUSION: The results suggested that the constituents from A.
      glabra may contain effective compounds which can be used as anticancer agents.

PMID- 25856712
TI  - Inhibitory effect of plant phenolics on fMLP-induced intracellular calcium rise
      and chemiluminescence of human polymorphonuclear leukocytes and their chemotactic
      activity in vitro.
AB  - CONTEXT: Polymorphonuclear leukocytes (PMNs) produce oxidants, contributing to
      systemic oxidative stress. Diets rich in plant polyphenols seem to decrease the
      risk of oxidative stress-induced disorders including cardiovascular disease.
      OBJECTIVE: The objective of this study was to examine the in vitro effect of each
      of the 14 polyphenols on PMNs chemotaxis, intracellular calcium response,
      oxidants production. MATERIALS AND METHODS: Blood samples and PMNs suspensions
      were obtained from 60 healthy non-smoking donors and incubated with a selected
      polyphenol (0.5-10 uM) or a control solvent. We assessed resting and fMLP
      dependent changes of intracellular calcium concentration ([Ca(2+)]i) in PMNs with
      the Fura-2AM method and measured fMLP-induced luminol enhanced whole blood
      chemiluminescence (fMLP-LBCL). Polyphenol chemoattractant activity for PMNs was
      tested with Boyden chambers. RESULTS: Polyphenols had no effect on resting
      [Ca(2+)]i. Unaffected by other compounds, fMLP-dependent increase of [Ca(2+)]i
      was inhibited by quercetin and catechol (5 uM) by 32 +/- 14 and 12 +/- 10% (p <
      0.04), respectively. Seven of the 14 tested substances (5 uM) influenced fMLP
      LBCL by decreasing it. Catechol, quercetin, and gallic acid acted most potently
      reducing fMLP-LBCL by 49 +/- 5, 42 +/- 15, and 28 +/- 18% (p < 0.05),
      respectively. 3,4-Dihydroxyhydrocinnamic, 3,4-dihydroxyphenylacetic, 4
      hydroxybenzoic acid, and catechin (5 uM) revealed distinct (p < 0.02)
      chemoattractant activity with a chemotactic index of 1.9 +/- 0.8, 1.8 +/- 0.7,
      1.6 +/- 0.6, 1.4 +/- 0.2, respectively. CONCLUSION AND DISCUSSION: Catechol,
      quercetin, and gallic acid at concentrations commensurate in human plasma
      strongly suppressed the oxidative response of PMNs. Regarding quercetin and
      catechol, this could result from an inhibition of [Ca(2+)]i response.

PMID- 25856713
TI  - In vitro antioxidant and anti-cholinesterase activities of Rhizophora mucronata.
AB  - CONTEXT: Rhizophora mucronata Lam. (Rhizophoraceae), commonly known as Asiatic
      mangrove, has been used traditionally among Asian countries as folk medicine.
      OBJECTIVE: This study investigates the cholinesterase inhibitory potential and
      antioxidant activities of R. mucronata. MATERIALS AND METHOD: Rhizophora
      mucronata leaves were successively extracted using solvents of varying polarity
      and a dosage of 100-500 ug/ml were used for each assay. Acetylcholinesterase
      (AChE) and butyrylcholinesterase (BChE) inhibitory activities were assessed
      according to the method of Ellman. In vitro antioxidant activity was assessed
      using free radical scavenging, reducing power, and metal-chelating activity
      (duration - 3 months). Total phenolic and flavonoid content were quantified
      spectrophotometrically. Compound characterization was done using column
      chromatography, NMR, FTIR, and LC-MS analysis. RESULTS: Methanolic leaf extract
      (500 ug/ml) exhibited the highest inhibitory activity against AChE (92.73 +/-
      0.54%) and BuChE (98.98 +/- 0.17%), with an IC50 value of 59.31 +/- 0.35 and
      51.72 +/- 0.33 ug/ml, respectively. Among the different solvent extracts,
      methanolic extract exhibited the highest antioxidant activity with an IC50 value
      of 47.39 +/- 0.43, 401.45 +/- 18.52, 80.23 +/- 0.70, and 316.47 +/- 3.56 ug/ml
      for DPPH, hydroxyl, nitric oxide radical, and hydrogen peroxide, respectively.
      Total polyphenolic and flavonoid contents in methanolic extract were observed to
      be 598.13 +/- 1.85 ug of gallic acid equivalent and 48.85 +/- 0.70 MUg of rutin
      equivalent/mg of extract. Compound characterization illustrated (+)-catechin as
      the bioactive compound responsible for cholinesterase inhibitory and antioxidant
      activities. CONCLUSION: The presence of rich source of flavonoids, in particular
      catechin, might be responsible for its cholinesterase inhibitory and antioxidant
      activities.

PMID- 25856714
TI  - Leonurine hydrochloride induces apoptosis of H292 lung cancer cell by a
      mitochondria-dependent pathway.
AB  - CONTEXT: Leonurine hydrochloride (LH), a major alkaloid compound extracted from
      Leonurus japonicas Houtt. (Labiatae), is considered to have antitumor roles.
      OBJECTIVE: This study investigated its effects on human non-small cell lung
      cancer (NSCLC) H292 cells and illustrated the possible mechanism involved.
      MATERIALS AND METHODS: After treatment with different concentrations of LH (0,
      10, 25, and 50 MUmol/L) for 6, 12, 24, 48, and 72 h, the cell viability was
      assessed by the MTT assay. After exposed to different doses of LH for 24 h, cell
      cycle distribution, cell apoptosis, mitochondrial membrane potential (MMP), and
      reactive oxygen species (ROS) were monitored by flow cytometry. RT-PCR and
      western blot were used to detect the expression of apoptosis-related genes.
      RESULTS: LH significantly inhibited the proliferation of H292 cells in a time-
      and dose-dependent manner, and induced G0/G1 cell-cycle arrest. Coincidentally,
      LH treatment at a dose of 10, 25, and 50 MUmol/L for 24 h increased apoptotic
      ratio from 4.9 +/- 0.43% to 11.5 +/- 1.12%, 19.3 +/- 1.16%, and 61.3 +/- 6.69%,
      respectively. The inhibition effect of LH on H292 cells was associated with the
      loss of MMP and the generation of ROS. The phosphorylation level of p38 was
      increased and Akt phosphorylation was reduced by LH treatment. Furthermore, LH
      treatment increased the expression levels of caspase-3, caspase-9 and Bax/Bcl-2.
      CONCLUSIONS: LH inhibits the proliferation and induces the apoptosis of H292
      cells in a mitochondria-dependent pathway, and the specific mechanism need to be
      further explored.

PMID- 25856715
TI  - Protective effect of kombucha on rats fed a hypercholesterolemic diet is mediated
      by its antioxidant activity.
AB  - CONTEXT: Kombucha (KT) is claimed to have various beneficial effects on human
      health, but there is very little scientific evidence available in the literature.
      OBJECTIVE: The present study investigates the effects of Camellia sinensis (GT)
      Linn. (Theaceae) and KT, two natural drinks, on cholesterol and antioxidant
      status using a hypercholesterolemia rat model. MATERIALS AND METHODS: The present
      study compared the free-radical scavenging abilities and polyphenol levels of GT
      and KT. Wistar rats fed cholesterol-rich diets were given KT or GT (5 mL/kg body
      weight per day, po) for 16 weeks, then fasted overnight and sacrificed. The
      plasma lipid levels, thiobarbituric acid reactive substances (TBARS) and
      aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma
      glutamyl transpeptidase (GGT) serum levels, antioxidant activities of superoxide
      dismutase (SOD) and catalase (CAT), and creatinine and urea rats were examined.
      RESULTS: KT had a phenolic compound of 955 +/- 0.75 mg GAE/g) followed, by GT
      (788.92 +/- 0.02 mg GAE/g). The free radical scavenging activity of KT was higher
      than GT. Compared with GT, KT induced lowered serum levels of TC, TG, VLDL-C, and
      LDL-C by 26, 27, 28, and 36%, respectively, and increased the serum level of high
      density lipoprotein cholesterol (HDL-C). KT induced a 55% decrease of TBARS level
      in liver and 44% in kidney, compared with those of rats fed a cholesterol-rich
      diet alone. Moreover, CAT and SOD activities were reduced by 29 and 33%,
      respectively, in liver and 31 and 35%, respectively, in kidney, after oral
      administration of KT, compared with those of HCD-fed rats. CONCLUSION: The
      findings revealed that KT administration induced attractive curative effects on
      hypercholesterolemic, particularly in terms of liver-kidney functions in rats.
      Its effect on humans needs to be studied further.

PMID- 25856716
TI  - Anti-inflammatory constituents from Perovskia atriplicifolia.
AB  - CONTEXT: Perovskia atriplicifolia Benth (Labiantae) has long been used as a
      traditional herbal medicine for anti-inflammation in Pakistan; this prompted us
      to isolate anti-inflammatory compounds from this plant. OBJECTIVE: The objective
      of this study was to isolate and characterize the anti-inflammatory principles
      from Perovskia atriplicifolia. MATERIALS AND METHODS: The CHCl3-soluble fraction
      of the methanol extract of the whole plant on column chromatography yielded
      compounds 1-6. The anti-inflammatory potential of the compounds 1-6 was evaluated
      by Leukotriene C4 (LTC4) Release Assay which was performed according to the
      established protocol. LTC4 in the supernatant of each well was measured using an
      ELISA kit (Cayman Chemical Co., Ann Arbor, MI). RESULTS: The bioassay-guided
      phytochemical investigation of the CHCl3 soluble fraction of the methanol extract
      of Perovskia atriplicifolia furnished six compounds, abrotanone (1), abrotandiol
      (2), (+)-pinoresinol (3), (+)-syringaresinol (4), (+)-lariciresinol (5), and (+)
      taxiresinol (6). The compounds (1-6) were evaluated for their inhibitory
      activities on LTC4 release. Among the tested compounds, (+)-taxiresinol (6)
      exhibited the most potent inhibition of LTC4 release with an IC50 value of 3.4 +/
      0.09 uM followed by compounds 4, 5, 3, and 2 with an IC50 value ranging from 7.9
      +/- 0.04 to 17.2 +/- 0.07 uM. Abrotanone (1) showed the lowest inhibition of LTC4
      release with an IC50 value of 35.1 +/- 0.05 uM (the positive control, zileuton,
      0.77 +/- 0.05 uM). CONCLUSION: Compounds 1-6 were found to possess inhibitory
      activity and seem to have potential therapeutic effect on inflammatory diseases.

PMID- 25856717
TI  - Antibacterial assay-guided isolation of active compounds from Artocarpus
      heterophyllus heartwoods.
AB  - CONTEXT: Preparations from Artocarpus heterophyllus Lam. (Moraceae) heartwoods
      are used in the traditional folk medicine for the treatment of inflammation,
      malarial fever, and to prevent bacterial and fungal infections. OBJECTIVE: The
      objective of this study was to isolate pure antibacterial compounds from A.
      heterophyllus heartwoods. MATERIALS AND METHODS: The dried and powdered A.
      heterophyllus heartwoods were successively extracted with the following solvents:
      hexane, ethyl acetate, and methanol. Each of the extracts was screened for their
      antibacterial activities using a disc diffusion method (10 mg/disc). Their
      minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations
      (MBCs) were determined using a broth microdilution method. The extract that
      showed the strongest antibacterial activities was fractionated to isolate the
      active compounds by an antibacterial assay-guided isolation process. RESULTS AND
      DISCUSSION: The ethyl acetate extract exhibited the strongest antibacterial
      activities against Streptococcus mutans, S. pyogenes, and Bacillus subtilis with
      MIC values of 78, 39, and 9.8 ug/mL, respectively. Based on an antibacterial
      assay-guided isolation, four antibacterial compounds: cycloartocarpin (1),
      artocarpin (2), artocarpanone (3), and cyanomaclurin (4) were purified. Among
      these isolated compounds, artocarpin exhibited the strongest antibacterial
      activity against Gram-positive bacteria, including S. mutans, S. pyogenes, B.
      subtilis, Staphylococcus aureus, and S. epidermidis with MICs of 4.4, 4.4, 17.8,
      8.9, and 8.9 uM, respectively, and MBCs of 8.9, 8.9, 17.8, 8.9, and 8.9 uM,
      respectively, while artocarpanone showed the strongest activity against
      Escherichia coli, a Gram-negative bacteria with MIC and MBC values of 12.9 and
      25.8 uM, respectively. Only artocarpin showed inhibitory activity against
      Pseudomonas aeruginosa with an MIC of 286.4 uM.

PMID- 25856718
TI  - Ameliorative effects of physcion 8-O-beta-glucopyranoside isolated from Polygonum
      cuspidatum on learning and memory in dementia rats induced by Abeta1-40.
AB  - CONTEXT: Polygonum cuspidatum Sieb. Et Zucc. (Polygonaceae) has been
      traditionally used in folk medicine to treat various diseases. OBJECTIVE: This
      study investigates the ameliorative effects of physcion 8-O-beta-glucopyranoside
      (PSG) isolated from P. cuspidatum on learning and memory in dementia rats induced
      by Abeta1-40. MATERIALS AND METHODS: Dementia rats were prepared by
      intracerebroventricular injection of Abeta1-40. PSG (5, 10, 20, and 40 mg/kg/d,
      for 5 d) was administered orally. Ameliorative activity of PSG in dementia rats
      was evaluated by the Morris water maze (MWM) test, and its mechanisms were
      explored by evaluating AchE activity, levels of DA, NE, and 5-HT in hippocampus,
      and drebrin protein expressions in hippocampus. RESULTS: Our results indicated
      that PSG (5, 10, 20, and 40 mg/kg/d) significantly inhibited the prolonged
      latency in dementia rats (p < 0.05), and inhibitory rates were 16.5, 22.7, 33.0,
      and 44.8% after 5 d of learning, indicating that PSG improves learning and memory
      of dementia rats. Furthermore, PSG significantly decreased AchE activity (10, 20,
      and 40 mg/kg/d; p < 0.05), increased 5-HT (20 and 40 mg/kg/d, p < 0.05), NE (10,
      20, and 40 mg/kg/d; p < 0.05), and DA levels (5, 10, 20, and 40 mg/kg; p < 0.05)
      in the hippocampus. Additionally, PSG obviously decreased the Abeta contents in
      hippocampus (10, 20, and 40 mg/kg/d; p < 0.05), and up-regulated drebrin protein
      expressions (5, 10, 20, and 40 mg/kg/d; p < 0.05). CONCLUSIONS: PSG can
      significantly enhance learning and memory in Abeta1-40-induced dementia rats, and
      the mechanisms may be related to increase levels of Ach, 5-HT, NE, and DA,
      decrease Abeta contents, and up-regulation of drebrin proteins in hippocampus.

PMID- 25856719
TI  - The effect of some antibiotics on glutathione reductase enzyme purified from
      liver and erythrocyte of Lake Van pearl mullet.
AB  - CONTEXT: The effect of antibiotics (amikacin, cefazolin, ivermectin, and
      kanamycin) on glutathione reductase (GR) isoenzymes activity in liver and
      erythrocyte of the fish, Chalcalburnus tarichi (Lake Van pearl mullet, Pallas
      1811) (Cyprinidae) were investigated. OBJECTIVE: This study determined the
      biochemical characterization of GR purified from the liver and erythrocytes of C.
      tarichi and the inhibition effect of the antibiotics on the GR isoenzymes.
      MATERIALS AND METHODS: GR was purified by affinity chromatography from the
      tissues of C. tarichi. The biochemical characterization of GR such as optimum
      temperature, optimum pH, and ionic strength were determined. The inhibition
      effects of the antibiotics on the isoenzymes were evaluated as IC50 and Ki
      values. Ki constant and 50% inhibitory concentration (IC50) value for antibiotics
      were determined by Lineweaver-Burk graphs and plotting activity % versus [I],
      respectively, at five different concentrations of antibiotics. RESULTS: Optimum
      temperature, pH, and ionic strength were determined for isoenzymes as 40  degrees
      C, 60  degrees C; 8.0, 8.0, and 50, 50 mM, respectively. Subunit molecular
      weights of the isoenzymes were estimated as 55 kDa by sodium dodecyl sulfate
      polyacrilamide gel electrophoresis (SDS-PAGE). In addition, IC50 and Ki values
      were calculated for amikacin, cefazolin, ivermectin, and kanamycin. The
      antibiotics showed non-competitive inhibition effects. IC50 values were
      calculated as 16.3, 36.6, 0.504, and 18.8 mM for liver and 20.0, 30.4, 0.787, and
      31.8 mM for erythrocyte, respectively. Ki constants were 13.9, 18.4, 0.654, and
      11.2 mM for liver and 23.2, 46.4, 1.19, and 36.4 mM for erythrocyte,
      respectively. DISCUSSION AND CONCLUSION: The results indicated that the
      antibiotics displayed non-competitive inhibition.

PMID- 25856720
TI  - Anticonvulsant activity of aqueous fraction of Carissa edulis root bark.
AB  - CONTEXT: Carissa edulis Vahl (Apocynaceae) is used in Nigerian folk medicine to
      manage a plethora of diseases including epilepsy, cancer, and inflammation; its
      efficacy is widely acclaimed among communities of northern Nigeria. OBJECTIVE:
      This study establishes anticonvulsant activities of aqueous fraction of ethanol
      root bark extract of Carissa edulis (RAF) and sub-fractions (S1 and S2) in animal
      models. MATERIALS AND METHODS: We evaluated the acute toxicity of the RAF, S1 and
      S2, and the anticonvulsant activity using pentylenetetrazole (PTZ), picrotoxin,
      strychnine, N-methyl-d-aspartate (NMDA), isoniazid (INH), and aminophylline
      induced seizures in mice. Their effects on maximal electroshock (MES) and
      kindling-induced seizures were studied in chicks and in rats, respectively, and
      in the electrophysiological study. The doses used for RAF were 150, 300, and 600
      mg/kg while S1 and S2 were 250, 500, and 1000 mg/kg. Both RAF and sub-fractions
      were administered once during the experiment. RESULTS: The intraperitoneal LD50
      of the RAF was estimated to be 2222.61 mg/kg and that of the S1 and S2 were above
      5000 mg/kg. RAF protected the mice by 50% while sub-fractions by 16.67% against
      PTZ-induced seizures. RAF offered 33.33 and 16.67% protection against strychnine
      and NMDA models, respectively. However, RAF offered 66.67-33.33% protections
      against aminophylline-induced seizures at doses of 150 and 600 mg/kg, but RAF,
      S1, and S2 had no effect on MES-induced seizures. DISCUSSION AND CONCLUSION: Our
      results validate the use of the plant traditionally in the management of
      epilepsy, thus supporting the appraisal of biologically active components of this
      plant as antiepileptic agents.

PMID- 25856721
TI  - Cognitive Decline and Hearing Health Care for Older Adults.
AB  - PURPOSE: The purpose of this article is to consider the implications of age
      related cognitive decline for hearing health care. METHOD: Recent research and
      current thinking about age-related declines in cognition and the links between
      auditory and cognitive aging are reviewed briefly. Implications of this research
      for improving prevention, assessment, and intervention in audiologic practice and
      for enhancing interprofessional teamwork are highlighted. CONCLUSIONS: Given the
      important connection between auditory and cognitive aging and given the high
      prevalence of both hearing and cognitive impairments in the oldest older adults,
      health care services could be improved by taking into account how both the ear
      and the brain change over the life span. By incorporating cognitive factors into
      audiologic prevention, assessment, and intervention, hearing health care can
      contribute to better hearing and communication as well as to healthy aging.

PMID- 25856722
TI  - A new and general model to describe, characterize, quantify and classify the
      interactive effects of temperature and pH on the activity of enzymes.
AB  - We suggest a new and general model to describe the effects of temperature (T) and
      pH on the catalytic activity of enzymes. Despite the abundance of models to
      describe those effects, the current proposals are unsatisfactory, except for
      specific experimental cases in which the interactive mechanism between the two
      variables does not exist. For both variables, our solution analyses the activated
      and deactivated phases of an enzyme as phenomena of different nature. The system
      is described with independent probability functions. The interactive effects
      between T and pH are introduced with simple auxiliary functions. These functions
      describe the variations induced by each variable in the parameters that define
      the effects of the other. The structure of the resulting equation is, in theory
      and practice, very regular, which facilitates its use, and it is highly
      descriptive in different scenarios with or without interactive effects. The model
      was tested on three different enzymatic systems which are specifically designed
      to produce data for the evaluation of the effect of T and pH on the enzyme
      activity (A). Afterwards, our model was validated using results from other
      authors. Briefly, the authors found that: (1) other available models that were
      compared with our proposal were inefficient and in all cases our model provided
      the only statistically consistent solution; (2) in four cases, the enzymatic
      activity could only be explained if interactive effects are accepted; (3) synergy
      and antagonism concepts for the interaction between T and pH were described and
      classified; and (4) our solution is universal and independent of the structure of
      an enzyme and the reaction concerned. 

PMID- 25856723
TI  - Perioperative Assessment and Management for Sleep Apnea in the Ambulatory
      Surgical Patient.
AB  - The overwhelming majority of surgical procedures performed in the United States
      are done on an outpatient basis. Patients with complicated medical problems are
      routinely scheduled for ambulatory procedures that have become progressively more
      complex. Appropriate patient selection is paramount to ensuring optimal
      perioperative outcomes, and the patient with known or suspected OSA presents
      unique challenges to the anesthesia care team regarding airway management, pain
      control, and postoperative monitoring requirements. Currently, a relative paucity
      of high-quality evidence exists on which to base guidelines or recommendations
      for the anesthetic care of these patients. It is generally agreed that early
      identification of those at risk for OSA allows for planning and implementation of
      strategies to help to reduce the risk of adverse perioperative events. Although
      various national societies have published consensus statements aimed at guiding
      the perioperative management of the patient at risk for OSA, more studies are
      needed to define the optimal approach to the perioperative care of this
      population. 

PMID- 25856724
TI  - Making Teamwork Work: Team Knowledge for Team Effectiveness.
AB  - This study examined the impact of two types of team knowledge on team
      effectiveness. The study assessed the impact of taskwork knowledge and teamwork
      knowledge on team satisfaction and performance. A longitudinal study was
      conducted with 27 service-management teams involving 178 students in a real-life
      restaurant setting. Teamwork knowledge was found to impact both team outcomes.
      Furthermore, team learning behavior was found to mediate the relationships
      between teamwork knowledge and team outcomes. Educators and managers should
      therefore ensure these types of knowledge are developed in teams along with
      learning behavior for maximum effectiveness.

PMID- 25856725
TI  - Genomic studies on the nature of species: adaptation and speciation in Mimulus.
AB  - Evolutionary biology is in an exciting era, in which powerful genomic tools make
      the answers accessible to long-standing questions about variation, adaptation and
      speciation. The availability of a suite of genomic resources, a shared knowledge
      base and a long history of study have made the phenotypically diverse plant genus
      Mimulus an important system for understanding ecological and evolutionary
      processes. An international Mimulus Research Meeting was held at Duke University
      in June 2014 to discuss developments in ecological and evolutionary genetic
      studies in Mimulus. Here, we report major recent discoveries presented at the
      meeting that use genomic approaches to advance our understanding of three major
      themes: the parallel genetic basis of adaptation; the ecological genomics of
      speciation; and the evolutionary significance of structural genetic variation. We
      also suggest future research directions for studies of Mimulus and highlight
      challenges faced when developing new ecological and evolutionary model systems. 

PMID- 25856726
TI  - Effectiveness of a psychoeducational programme for informal caregivers of older
      adults.
AB  - PURPOSE OF THE STUDY: This study explored the effectiveness of psychoeducational
      programme for informal caregivers called 'Caring at home'. DESIGN AND METHODS:
      The sample included 60 informal caregivers of elderly people (>=60 years) living
      in the community. Socio-demographic information of informal caregivers and care
      receivers was collected with the COPE Index. The assessment protocol comprised
      four scales: 12-item Short-Form Health Survey, General Health Questionnaire-12,
      Positive Aspects of Caregiving and Caregiver Strain Index Modified. There were
      five assessment moments: a pretest, a post-test and three follow-ups. RESULTS:
      Informal caregivers had an average age of 52.08 years (SD = 9.11) and were mainly
      women (90.0%), married/partnered (75.0%) and children of the care recipients
      (61.7%). The median time spent in care was 12 hours/day (IQR = 18). Results
      showed a favourable evolution after the psychoeducational intervention, a
      significant improvement in caregivers' mental health (p = 0.03) from pretest to
      1st follow-up (2/3 months after the psychoeducational intervention) and the
      maintenance of the other assessed dimensions of the caregivers' behaviour.
      IMPLICATIONS: The psychoeducational intervention seems to promote improvements in
      mental health and the maintenance of other favourable conditions at baseline.
      These results may indicate that psychoeducational programme are beneficial to
      minimise or prevent adverse effects of caregiving.

PMID- 25856730
TI  - High-quality, large-area MoSe2 and MoSe2/Bi2Se3 heterostructures on
      AlN(0001)/Si(111) substrates by molecular beam epitaxy.
AB  - Atomically-thin, inherently 2D semiconductors offer thickness scaling of
      nanoelectronic devices and excellent response to light for low-power versatile
      applications. Using small exfoliated flakes, advanced devices and integrated
      circuits have already been realized, showing great potential to impact
      nanoelectronics. Here, high-quality single-crystal MoSe2 is grown by molecular
      beam epitaxy on AlN(0001)/Si(111), showing the potential for scaling up growth to
      low-cost, large-area substrates for mass production. The MoSe2 layers are
      epitaxially aligned with the aluminum nitride (AlN) lattice, showing a uniform,
      smooth surface and interfaces with no reaction or intermixing, and with
      sufficiently high band offsets. High-quality single-layer MoSe2 is obtained, with
      a direct gap evidenced by angle-resolved photoemission spectroscopy and further
      confirmed by Raman and intense room temperature photoluminescence. The successful
      growth of high-quality MoSe2/Bi2Se3 multilayers on AlN shows promise for novel
      devices exploiting the non-trivial topological properties of Bi2Se3. 

PMID- 25856731
TI  - Synthesis of 6,8,9 poly-substituted purine analogue libraries as pro-apoptotic
      inducers of human leukemic lymphocytes and DAPK-1 inhibitors.
AB  - A 18-member library of 6,8,9-poly-substituted purines was prepared from
      pyrimidines, primary alcohols, and N,N-dimethylamides under basic conditions via
      a novel one-pot synthetic pathway controlled by amide sizes and the novel
      analogues were tested against two leukemia cell lines: Jurkat (acute T cell
      leukemia) and K562 (chronic erythroleukemia) cells. Compounds having a benzoxy
      group at C6 position of the aromatic ring exhibited antiproliferative activity in
      Jurkat cells whereas all compounds induced a lower effect on K562 cells. Analysis
      of cell cycle, Annexin-V staining, and cleavage of initiator caspases assays
      showed that the active purine analogues induce cell death by apoptosis. Based on
      these results, a new purine derivative was synthesized, 6-benzyloxy-9-tert-butyl
      8-phenyl-9H-purine (6d), which displayed the highest activity of the series
      against Jurkat cell lines. Finally, (33)P-radiolabeled kinase assays using 96
      recombinant human kinases known to be involved in apoptotic events were
      performed. Just one of the kinases tested, DAPK-1, was inhibited 50% or more by
      the phenotypic hits at 10 MUM, suggesting that the inhibition of this target
      could be responsible for the induction of cell death by apoptosis. In agreement
      with the phenotypic results, the most active antiproliferative agent, 6d,
      displayed also the lowest IC50 value against recombinant DAPK1 (2.5 MUM), further
      supporting the potential role of this protein on the observed functional
      response. DAPK-1 inhibition led by 6d together with its pro-apoptotic properties
      against the Jurkat line makes it an interesting candidate to further investigate
      the role of DAPK1 kinase in triggering apoptosis in cancer cells, a role which is
      attracting recent interest.

PMID- 25856732
TI  - Effectiveness of Repeated Courses of Pulmonary Rehabilitation on Functional
      Exercise Capacity in Patients With COPD.
AB  - PURPOSE: To determine whether an as-needed repeated pulmonary rehabilitation (PR)
      intervention produces a clinically important improvement in exercise capacity.
      METHODS: The study included a retrospective analysis of characteristics and 6
      minute walk distance (6MWD) of patients with chronic obstructive pulmonary
      disease (COPD) who completed PR at 2 centers. Data were abstracted from all
      patients with COPD completing 2 courses of rehabilitation and those of randomly
      sampled patients completing only 1 course of PR. RESULTS: We identified 37
      repeaters and selected 69 nonrepeaters for analysis. No significant differences
      between the 2 groups with regard to age, FEV1 percent predicted, gender, initial
      6MWD, improvement in 6MWD, and the percentage of patients achieving the minimal
      important difference (MID) of >= 35 m were observed with the completion of the
      first rehabilitation. The time between the first and second PR interventions was
      a mean of 45 +/- 24 months. Repeating patients had a decrease of 90 +/- 76 m in
      6MWD at the beginning of the second rehabilitation course compared with the end
      of the first intervention (P = .001). Twenty-four (65%) of repeating patients
      achieved the MID in 6MWD at the end of the second course of PR. Those who
      achieved the MID in 6MWD during the second course of rehabilitation also tended
      to have attained greater improvement in this outcome during the first course (P =
      .07). CONCLUSION: Two-thirds of patients with COPD undergoing repeat PR
      experienced significant improvement in exercise capacity. Offering PR to patients
      with COPD on an as-needed basis appears to be beneficial even after a prolonged
      period of time between the interventions.

PMID- 25856733
TI  - A practical review for cardiac rehabilitation professionals of continuous-flow
      left ventricular assist devices: historical and current perspectives.
AB  - An increasing number of patients with end-stage heart failure are being treated
      with continuous-flow left ventricular assist devices (cf-LVADs). These patients
      provide new challenges to the staff in exercise-based cardiac rehabilitation (CR)
      programs. Even though experience remains limited, it seems that patients
      supported by cf-LVADs may safely engage in typical rehabilitative activities,
      provided that some attention is paid to specific aspects, such as the presence of
      a short external drive line. In spite of initial physical deconditioning, CR
      allows progressive improvement of symptoms such as fatigue and dyspnea. Intensity
      of rehabilitative activities should ideally be based on measured aerobic capacity
      and increased appropriately over time. Regular, long-term exercise training
      results in improved physical fitness and survival rates. Appropriate adjustment
      of cf-LVAD settings, together with maintenance of adequate blood volume, provides
      maximal output, while avoiding suction effects. Ventricular arrhythmias, although
      not necessarily constituting an immediate life-threatening situation, deserve
      treatment as they could lead to an increased rate of hospitalization and poorer
      quality of life. Atrial fibrillation may worsen symptoms of right ventricular
      failure and reduce exercise tolerance. Blood pressure measurements are possible
      in cf-LVAD patients only using a Doppler technique, and a mean blood pressure
      <=80 mmHg is considered "ideal." Some patients may present with orthostatic
      intolerance, related to autonomic dysfunction. While exercise training
      constitutes the basic rehabilitative tool, a comprehensive intervention that
      includes psychological and social support could better meet the complex needs of
      patients in which cf-LVAD may offer prolonged survival. 

PMID- 25856734
TI  - Controlled release of rhEGF and rhbFGF from electrospun scaffolds for skin
      regeneration.
AB  - Controlled delivery of multiple therapeutic agents can be considered as an
      effective approach in skin tissue engineering. In this study, recombinant human
      epidermal growth factor (rhEGF) and recombinant human basic fibroblast growth
      factor (rhbFGF) encapsulated in PLGA microspheres were loaded in hybrid scaffolds
      of PLGA and PEO. The scaffolds with various formulations were fabricated through
      electrospinning in order to maintain dual, individual or different release rate
      of rhEGF and rhbFGF. Morphological, physical and mechanical properties of the
      scaffold were investigated. The scaffold possessed uniform morphology with an
      average diameter of 280 nm for PLGA and 760 nm for PEO nanofibers. Furthermore,
      the mechanical properties of the scaffolds were shown to be akin to those of
      human skin. Bioactivity of the scaffolds for human skin fibroblasts was
      evaluated. The HSF acquired significant proliferation and well-spread morphology
      on the scaffolds particularly in the case of different release rate of rhEGF and
      rhbFGF which implies the synergistic effect of the growth factors. Additionally,
      collagen and elastin gene expression was significantly up-regulated in the HSF
      seeded on the scaffolds in the case of individual delivery of rhEGF and dual
      delivery of rhEGF and rhbFGF. In conclusion, the prepared scaffolds as a suitable
      supportive substrate and multiple growth factor delivery system can find
      extensive utilization in skin tissue engineering.

PMID- 25856735
TI  - Psychosocial concerns of cancer patients in Singapore.
AB  - AIMS: Psychosocial needs are high among cancer patients, and screening for these
      is recognized as integral to quality cancer care. This study identified the
      psychosocial needs of cancer patients at their first visit at a hematology
      oncology clinic. METHODS: Fifty-four new consecutive patients completed the
      Distress Thermometer and the Problem List, the Hospital Anxiety and Depression
      Scale, and the EuroQol Quality of Life Scale at their first visit to plan for
      chemotherapy. Data were analyzed with SPSS. RESULTS: Analyses revealed that
      participants had an average of 2.8 +/- 2.3 problems, with 82% having psychosocial
      needs. Emotional concerns formed the top four psychosocial needs of the cohort
      (worry 46%, fears 26%, nervousness 26%, sadness 24%), with the fifth being a
      practical concern (insurance/finance 22%). The former were more frequent among 41
      to 50-year-olds and significantly correlated with distress scores. Practical
      concerns were significantly correlated with depressive symptoms. Family concerns
      were more significant in women. The overall score on the Problem List correlated
      with distress, anxious symptomatology and poorer quality of life scores.
      CONCLUSIONS: Distress and psychosocial needs are high in cancer patients even at
      an early stage prior to chemotherapy. Attention to these needs is crucial as they
      cause significant distress and affect the patient's quality of life.

PMID- 25856736
TI  - Binding mode of an alpha-amino acid-linked quinoxaline-2,3-dione analogue at
      glutamate receptor subtype GluK1.
AB  - Two alpha-amino acid-functionalized quinoxalines, 1a (CNG-10301) and 1b (CNG
      10300), of a quinoxaline moiety coupled to an amino acid moiety were designed,
      synthesized, and characterized pharmacologically. While 1a displayed low affinity
      at native AMPA, KA, and NMDA receptors, and at homomeric GluK1,3 receptors, the
      affinity for GluK2 was in the midmicromolar range (Ki = 136 MUM), 1b displayed
      low to midmicromolar range binding affinity at all the iGluRs (Ki = 9-126 MUM).
      In functional experiments (outside-out patches excised from transfected HEK293T
      cells), 100 MUM 1a partially blocked GluK1 (33% peak response), while GluK2 was
      unaffected (96% peak response). Furthermore, 1a was shown not to be an agonist at
      GluK1 and GluK2 at 100 MUM. On the other hand, 100 MUM 1b fully antagonized GluK1
      (8% peak response) but only partially blocked GluK2 (33% peak response). An X-ray
      structure at 2.3 A resolution of 1b in the GluK1-LBD (ligand-binding domain)
      disclosed an unexpected binding mode compared to the predictions made during the
      design phase; the quinoxaline moiety remains to act as an amino acid bioisostere,
      but the amino acid moiety is oriented into a new area within the GluK1 receptor.
      The structure of the GluK1-LBD with 1b showed a large variation in domain
      openings of the three molecules from 25 degrees  to 49 degrees , demonstrating
      that the GluK1-LBD is capable of undergoing major domain movements. 

PMID- 25856737
TI  - Interfacial Charge Induced Magnetoelectric Coupling at BiFeO3/BaTiO3 Bilayer
      Interface.
AB  - Bilayer thin films of BiFeO3-BaTiO3 at different thicknesses of BiFeO3 were
      prepared by RF-magnetron sputtering technique. A pure phase polycrystalline
      growth of thin films was confirmed from XRD results. Significantly improved
      ferroelectric polarization (2Pr ~ 30 MUC/cm(2)) and magnetic moment (Ms ~ 33
      emu/cc) were observed at room temperature. Effect of ferroelectric polarization
      on current conduction across the interface has been explored. Accumulation and
      depletion of charges at the bilayer interface were analyzed by current-voltage
      measurements which were further confirmed from hysteretic dynamic resistance and
      capacitance voltage profiles. Magnetoelectric coupling due to induced charges at
      grain boundaries of bilayer interface was further investigated by room
      temperature magnetocapacitance analysis. A room temperature magnetocapacitance
      was found to originate from induced charge at the bilayer interface which can be
      manipulated by varying the thickness of BFO to obtain higher ME coupling
      coefficient. Dynamic magnetoelectric coupling was investigated, and maximum
      longitudinal magnetoelectric coupling was observed to be 61 mV/cm.Oe at 50 nm
      thickness of BiFeO3. The observed magnetoelectric properties are potentially
      useful for novel room temperature magnetoelectric and spintronic device
      applications. 

PMID- 25856738
TI  - [Do you know the CRPD? (Convention on the Rights of Persons with Disabilities)].

PMID- 25856739
TI  - [Comparison between the regions of Belgium with regard to the amounts of
      antipsychotics prescribed during the period 2004-2012: a national survey].
AB  - BACKGROUND: Antipsychotics are prescribed frequently to treat a wide range of
      psychiatric and non-psychiatric indications. Over the last few years there has
      been a marked increase in the use of antipsychotics. However, specific
      prescribing patterns seem to be determined mainly by regional and national
      differences. AIM: In this study we compare developments in the sales of
      antipsychotics in the three Belgian regions (Flanders, Wallonia and Brussels)
      between 2004 and 2012. METHOD: For our study we used data supplied by Pharmanet
      regarding the sales of their antipsychotics in Belgium. Pharmanet forms part of
      the National Institute for Health and Disability Insurance (RIZIV), which is the
      organisation responsible for collecting information about the prescription
      behaviour of Belgian doctors. RESULTS: Between 2004 and 2012 the sales of
      antipsychotics in Belgium increased by 57 %. Nevertheless, the low percentage of
      prescriptions for long-term use (6.6-8.7 % of the antipsychotics prescribed for a
      treatment period of six months or longer) suggests that several important groups
      of patients were being undertreated. Relative to the size of the population of
      Belgium as a whole, more antipsychotics were sold in Wallonia and Brussels than
      in Flanders, a trend that remained relatively stable over time, namely over the
      period 2004 and 2012. The preference for second-generation antipsychotics was
      more pronounced in Flanders and the shift to second-generation antipsychotics
      occurred faster in Flanders than in Wallonia and Brussels. CONCLUSION: In Belgium
      there seems a clear need for a more unified and rational policy with regards to
      the prescribing and use of psychotropic drugs.

PMID- 25856740
TI  - [Complex PTSD following early-childhood trauma: emotion-regulation training as
      addition to the PTSD guideline].
AB  - BACKGROUND: Posttraumatic stress disorder (PTSD) symptoms in individuals who have
      experienced repeated trauma (sexual and/or physical) in early childhood can lead
      to problems associated with emotion regulation, interpersonal functioning and
      self-image. This so-called complex PTSD is often accompanied by a comorbid
      personality disorder. Although ptsd is associated with structural and functional
      abnormalities in emotion-regulation areas in the brain, it is not known whether
      complex PTSD shows similar abnormalities. Experts take the view that before
      individuals with complex PTSD are given appropriate therapy they should receive a
      course of emotion-regulation therapy such as the one tested by Zlotnick e.a.
      (1997) in a randomised controlled trial (RCT).   AIM: To replicate Zlotnick's RCT
      in the Netherlands and to find out whether complex PTSD patients show specific
      structural and functional brain abnormalities and whether psychological recovery
      is linked to the 'normalisation' of these abnormalities. METHOD: In a RCT with
      complex PTSD patients (n = 71) who had experienced trauma in early childhood, we
      compared normal individual treatment with treatment supported by 'Before and
      beyond', which consists of emotion-regulation therapy combined with cognitive
      group therapy. In a subsample (n= 33) we also performed an mri (repeated, n = 9)
      in which individuals were required to execute an emotional memory and attention
      task. RESULTS: In complex PTSD, structural abnormalities in the brain seemed to
      be more extensive than in PTSD and brain activity in complex PTSD seemed to be
      strikingly different from the brain activity seen in PTSD patients who had
      experienced only single trauma. The results of the RCT indicate that 'Before and
      beyond' is a clinically meaningful treatment (with minimal drop-out) for complex
      PTSD patients with a variety of personality disorders. The psychological recovery
      of patients who received the emotion regulation and cognitive group treatment was
      associated with normalisation of brain function. CONCLUSION: Treatment guidelines
      for ptsd patients cannot be applied directly and automatically to complex PTSD
      because there is no scientific evidence to justify such a step. The
      neurobiological profile of PTSD differs from that of complex PTSD. Patients with
      complex PTSD seem to react favourably to emotion regulation therapy. This
      treatment therefore could be a useful addition to the current PTSD guideline for
      this specific group. There is a need for further research that focuses on complex
      PTSD patients.

PMID- 25856741
TI  - [Auto-immune disorders as a possible cause of neuropsychiatric syndromes].
AB  - BACKGROUND: Changes that occur in the behaviour of voltage-gated ion channels and
      ligand-gated receptor channels due to gene mutations or auto-immune attack are
      the cause of channelopathies in the central and peripheral nervous system.
      Although the relation between molecular channel defects and clinical symptoms has
      been explained in the case of many neuromuscular channelopathies, the
      pathophysiology of auto-immunity in neuropsychiatric syndromes is still unclear.
      AIM: To review recent findings regarding neuronal auto-immune reactions in severe
      neuropsychiatric syndromes. METHOD: Using PubMed, we consulted the literature
      published between 1990 and August 2014 relating to the occurrence of auto-immune
      antibodies in severe and persistent neuropsychiatric syndromes. RESULTS: Auto
      antibodies have only limited access to the central nervous system, but if they do
      enter the system they can, in some cases, cause disease. We discuss recent
      findings regarding the occurrence of auto-antibodies against ligand-activated
      receptor channels and potassium channels in neuropsychiatric and neurological
      syndromes, including schizophrenia and limbic encephalitis. CONCLUSION: Although
      the occurrence of several auto-antibodies in schizophrenia has been confirmed,
      there is still no proof of a causal relationship in the syndrome. We still have
      no evidence of the prevalence of auto-immunity in neuropsychiatric syndromes. The
      discovery that an antibody against an ion channel is associated with some
      neuropsychiatric disorders may mean that in future it will be possible to treat
      patients by means of immunosuppression, which could lead to an improvement in a
      patient's cognitive abilities.

PMID- 25856742
TI  - [Alcohol-induced psychotic disorder: a systematic literature review].
AB  - BACKGROUND: From the second half of the 19th century eminent psychiatrists began
      referring to alcohol-induced psychotic disorder (AIPD) as a specific alcoholic
      psychosis. Over the last decades interest in AIPD seems to have declined: the
      last review dates form 1989. AIM: To review the recent literature on AIPD, revive
      interest in the disorder, evaluate the current scientific evidence and assess its
      clinical value. METHOD: We performed a Medline search based on the following
      terms: 'Psychoses, Alcoholic' [Mesh] OR 'alcohol induced psychotic disorder' OR
      'alcoholic hallucinosis' OR 'alcohol hallucinosis'. Our search was restricted to
      articles written in English or Dutch and published between 1-1-1988 and 31-1
      2013. RESULTS: We found 164 papers, from which we selected 21 for further
      discussion. The quality of the papers selected was variable, most of the papers
      being the result of clinical research. The most important findings referred to
      epidemiology: 0.4% lifetime prevalence in the general population, 4.0% in
      patients with alcohol dependence. We found only limited evidence of
      psychopathological differentiation between delirium and primary psychotic
      disorder. Correct diagnosis of AIPD is important because of the implications
      regarding the length and nature of the treatment: short or long course of
      antipsychotics, referral to a substance-abuse unit. CONCLUSION: AIPD has survived
      as a clinical entity. However, scientific evidence of this is limited. Further
      research is needed because it is vitally important that the patient receives the
      most appropriate treatment.

PMID- 25856743
TI  - [Countertransference: from a psychoanalytical to a transtheoretical concept].
AB  - BACKGROUND: In classical psychoanalysis, countertransference reactions pointed to
      'unfinished business' on the part of the therapist. The therapist had to be able
      to control or eliminate his countertransference reactions in order to protect the
      patient from the effect of such reactions. According to psychoanalytical thinking
      today, however, countertransference is considered to be a joint creation of the
      patient and the therapist. AIM: To demonstrate how countertransference, which was
      originally a typical psychoanalytical concept, has evolved into a trans
      theoretical concept. METHOD: A selection of the voluminous literature is
      discussed. RESULTS: The countertransference, which was originally a
      psychoanalytical concept, has been modernised and updated and has been adopted by
      other psychotherapeutic systems. CONCLUSION: The current notion that
      countertransference is a concept created jointly by patient and therapist has led
      to increased interest among practitioners of other types of psychotherapy, making
      them aware of the diagnostic and therapeutic importance of countertransference.

PMID- 25856744
TI  - [Wernicke encephalopathy].
AB  - Wernicke encephalopathy is an acute neuropsychiatric disease with heterogeneous
      symptoms, including changes in mental status, ataxia and ocular abnormalities; if
      left untreated, these symptoms can lead to morbidity and even to mortality. The
      treatment is thiamine suppletion. Because of the heterogeneity of the symptoms
      and the high risk of morbidity and mortality if the symptoms are not treated, it
      is vitally important that on observing a patient's early symptoms the clinician
      immediately suspects that the symptoms could point to Wernicke encephalopathy. 

PMID- 25856745
TI  - [Psychiatric problems in a motor disorder: psychosis in Huntington's disease].
AB  - Huntington's disease is characterised by a triad of motor symptoms (choreic
      movements), psychiatric symptoms and cognitive decline. Much less is known about
      the psychiatric symptoms such as psychosis and anxiety than about the motor
      symptoms. We discuss the case of a patient with Huntington's disease and
      psychosis and comment on the possible types of medication that should be used. 

PMID- 25856746
TI  - PCSK9 inhibitors.
AB  - The discovery of proprotein convertase subtilisin kexin 9 (PCSK9) has
      considerably changed the therapeutic options in the field of lipid management.
      PCSK9 reduces LDL receptor recycling, leading to a decrease of low-density
      lipoprotein cholesterol (LDL-C) receptors on the surface of hepatocytes and a
      subsequent increase of circulating LDL-C levels. In observational studies, the
      loss-of-function mutations of PCSK9 have been associated with a reduction of LDL
      C levels and cardiovascular disease (CVD) events. In contrast, humans with high
      levels of PCSK9 have higher level of plasma LDL-C and significantly enhanced CVD
      risk during their lifetime, gain-of-function mutations on PCSK9 are, for
      instance, causatively associated with familial hypercholesterolaemia (FH).
      Inhibition of PCSK9 is therefore a promising therapeutic option for the lowering
      of LDL-C levels. The clinical development of human monoclonal antibodies against
      PCSK9 has progressed, with promising results reported from phase 2 clinical
      studies in patients with FH or intolerant to statin with LDL-C levels not on
      target levels. Phase I studies demonstrated safety and efficacy. In phase II, a
      60%-70% reduction in LDL-C was observed, especially when subcutaneous injections
      were performed regularly every two weeks. No significant side effects were
      observed, with the exception of injection site reactions. Three large phase III
      programmes with the new anti PCSK9 antibodies are currently underway in patients
      with acute coronary syndrome (ACS) and LDL-C inadequately controlled by standard
      treatments. The main objective of these studies is to evaluate the effect of
      PCSK9 inhibition on the occurrence of CVD events in patients with ACS. 

PMID- 25856747
TI  - Synthesis of aromatic aza-metallapentalenes from metallabenzene via sequential
      ring contraction/annulation.
AB  - The concept of aromaticity has long played an important role in chemistry and
      continues to fascinate both experimentalists and theoreticians. Among the
      archetypal aromatic compounds, heteroaromatics are particularly attractive.
      Recently, substitution of a transition-metal fragment for a carbon atom in the
      anti-aromatic hydrocarbon pentalene has led to the new heteroaromatic
      osmapentalenes. However, construction of the aza-homolog of osmapentalenes cannot
      be accomplished by a similar synthetic manipulation. Here, we report the
      synthesis of aza-osmapentalenes by sequential ring contraction/annulation
      reactions of osmabenzenes via osmapentafulvenes. Nuclear magnetic resonance
      spectra, X-ray crystallographic analysis, and DFT calculations all suggest that
      these aza-osmapentalenes exhibit aromatic character. Thus, the stepwise
      transformation of metallabenzenes to metallapentafulvenes and then aza
      metallapentalenes provides an efficient and facile synthetic route to these
      bicyclic heteroaromatics. 

PMID- 25856748
TI  - Lost in translation: an antiviral plant defense mechanism revealed.
AB  - Plant viruses depend on the host translational machinery to establish their
      infectious cycle. In a recent Nature publication, Zorzatto et al. (2015)
      highlight the suppression of the protein synthesis process as an antiviral
      defense mechanism in plants.

PMID- 25856749
TI  - Host autophagy combating S. aureus: alpha-toxin will be tolerated.
AB  - Autophagy regulates the degradation of both cellular components and invading
      intracellular pathogens. In this issue of Cell Host & Microbe, Maurer et al.
      (2015) reveal that cellular autophagy decreases host sensitivity to
      Staphylococcus aureus alpha-toxin via reduced expression of the toxin receptor
      ADAM10, thus rendering the host tolerant to disease.

PMID- 25856750
TI  - Calnexin bridges the gap toward a pan-fungal vaccine.
AB  - Vaccines are needed to combat the global rise in fungal diseases. In this issue
      of Cell Host & Microbe, Wuthrich et al. (2015) identify calnexin as a target of
      antigen-specific CD4 T cell responses against multiple fungal pathogens. This
      study illustrates that a conserved epitope triggers convergent cell-mediated
      immune responses to confer heterologous antifungal immunity.

PMID- 25856751
TI  - The multidimensional nature of antiviral innate immunity.
AB  - Viruses possess elaborate defensive mechanisms to evade host innate immune
      responses. In this issue of Cell Host & Microbe, Stavrou et al. (2015) reveal how
      the murine leukemia virus uses a sugar-protein shield to protect from inevitable
      destruction by cellular innate immune factors including the APOBEC3 DNA mutating
      enzyme.

PMID- 25856752
TI  - Two tales (tails) of SAMHD1 destruction by Vpx.
AB  - The lentivirus protein Vpx/Vpr recognizes the host restriction factor SAMHD1 at
      either its N- or C-terminal tail and targets it for destruction by the cellular
      protein degradation machinery. In this issue of Cell Host & Microbe, Schwefel et
      al. (2015) report the structural basis of SAMHD1 N-terminal targeting by Vpx.

PMID- 25856753
TI  - Delivery of cardiolipins to the Salmonella outer membrane is necessary for
      survival within host tissues and virulence.
AB  - The outer membrane (OM) of Gram-negative bacteria is an asymmetric lipid bilayer
      that serves as a barrier to the environment. During infection, Gram-negative
      bacteria remodel their OM to promote survival and replication within host
      tissues. Salmonella rely on the PhoPQ two-component regulators to coordinate OM
      remodeling in response to environmental cues. In a screen for mediators of PhoPQ
      regulated OM remodeling in Salmonella Typhimurium, we identified PbgA, a
      periplasmic domain-containing transmembrane protein, which binds cardiolipin
      glycerophospholipids near the inner membrane and promotes their PhoPQ-regulated
      trafficking to the OM. Purified-PbgA oligomers are tetrameric, and the
      periplasmic domain contains a globular region that binds to the OM in a PhoPQ
      dependent manner. Thus, PbgA forms a complex that may bridge the envelope for
      regulated cardiolipin delivery. PbgA globular region-deleted mutant bacteria are
      severely attenuated for pathogenesis, suggesting that increased cardiolipin
      trafficking to the OM is necessary for Salmonella to survive within host tissues
      that activate PhoPQ.

PMID- 25856756
TI  - Turning a "useless" ligand into a "useful" ligand: a magneto-structural study of
      an unusual family of Cu(II) wheels derived from functionalised phenolic oximes.
AB  - While the phenolic oximes (R-saoH2) are well known for producing monometallic
      complexes of the type [M(II)(R-saoH)2] with Cu(II) ions in near quantitative
      yield, their derivatisation opens the door to much more varied and interesting
      coordination chemistry. Here we show that combining the complimentary
      diethanolamine and phenolic oxime moieties into one organic framework (H4L1 and
      H4L2) allows for the preparation and isolation of an unusual family of [Cu(II)]n
      wheels, including saddle-shaped, single-stranded [Cu(II)8] wheels of general
      formula [Cu8(HL1)4(X)4](n)[Y] (when n = 0, X = Cl(-), NO3(-), AcO(-), N3(-); when
      n = 2+ X = (OAc)2/(2,2'-bpy)2 and Y = [BF4]2) and [Cu8(HL2)4(X)4] (X = Cl(-), Br(
      )), a rectangular [Cu6(HL1)4] wheel, and a heterometallic [Cu4Na2(HL1)2(H2L1)2]
      hexagon. Magnetic studies show very strong antiferromagnetic exchange between
      neighbouring metal ions, leading to diamagnetic ground states in all cases. DFT
      studies reveal that the magnitude of the exchange constants are correlated to the
      Cu-N-O-Cu dihedral angles, which in turn are correlated to the
      planarity/puckering of the [Cu(II)]n rings. 

PMID- 25856754
TI  - Molecular determinants for recognition of divergent SAMHD1 proteins by the
      lentiviral accessory protein Vpx.
AB  - The SAMHD1 triphosphohydrolase inhibits HIV-1 infection of myeloid and resting T
      cells by depleting dNTPs. To overcome SAMHD1, HIV-2 and some SIVs encode either
      of two lineages of the accessory protein Vpx that bind the SAMHD1 N or C terminus
      and redirect the host cullin-4 ubiquitin ligase to target SAMHD1 for proteasomal
      degradation. We present the ternary complex of Vpx from SIV that infects
      mandrills (SIVmnd-2) with the cullin-4 substrate receptor, DCAF1, and N-terminal
      and SAM domains from mandrill SAMHD1. The structure reveals details of Vpx
      lineage-specific targeting of SAMHD1 N-terminal "degron" sequences. Comparison
      with Vpx from SIV that infects sooty mangabeys (SIVsmm) complexed with SAMHD1
      DCAF1 identifies molecular determinants directing Vpx lineages to N- or C
      terminal SAMHD1 sequences. Inspection of the Vpx-DCAF1 interface also reveals
      conservation of Vpx with the evolutionally related HIV-1/SIV accessory protein
      Vpr. These data suggest a unified model for how Vpx and Vpr exploit DCAF1 to
      promote viral replication.

PMID- 25856755
TI  - Passively acquired antibody-dependent cellular cytotoxicity (ADCC) activity in
      HIV-infected infants is associated with reduced mortality.
AB  - In addition to direct effects on virus infectivity, antibodies mediate antibody
      dependent cellular cytotoxicity (ADCC), the killing of an antibody-coated virus
      infected cell by cytotoxic effector cells. Although ADCC has been suggested to
      protect against HIV, the relationship between HIV-specific ADCC antibodies at the
      time of HIV exposure and infection outcome in humans remains to be assessed. We
      evaluated the ADCC activity of passively acquired antibodies in infants born to
      HIV-infected mothers. ADCC levels were higher in uninfected than infected
      infants, although not significantly. Increase in ADCC antibody activity in
      infected infants was associated with reduced mortality risk. Infant ADCC
      positively correlated with the magnitude of IgG1 binding, and IgG1 levels were
      associated with survival in infected infants. Infant IgG3-binding antibodies were
      not associated with infected infant survival. These data suggest a therapeutic
      benefit of pre-existing HIV-specific ADCC antibodies and support a role for
      eliciting ADCC-mediating IgG1 in HIV vaccines.

PMID- 25856757
TI  - Rehabilitation following total hip arthroplasty evaluation over short follow-up
      time: randomized clinical trial.
AB  - Hip osteoarthritis (OA) is a degenerative disease, and total hip arthroplasty
      (THA) is one of the surgical procedures of choice to improve the OA patient's
      quality of life. Without a rehabilitation program, THA patients will develop
      functional limitations. A randomized double-blind trial was performed between
      July 2009 and October 2011 to compare in a short follow-up time two groups of
      patients who underwent THA for OA. The THA protocol (THAP) group received verbal
      instructions and physiotherapy exercise demonstrations, and the THA physiotherapy
      care protocol (THAPCP) group received the same verbal instructions and
      demonstrations associated with daily exercise practice guided by a
      physiotherapist. The outcomes that were assessed preoperatively and 15 d
      postoperatively in 106 patients were muscle strength force, goniometry, Medical
      Outcomes Study 36-Item Short Form Health Survey, and Merle d'Aubigne and Postel
      score. Higher muscle strength force scores and degrees in range of motion were
      found in the THAPCP group. Higher improvements were also observed for the THAPCP
      group compared with the THAP group in the Merle d'Aubigne and Postel score. At
      the end of the follow-up period, the intervention in the THAPCP group improved
      functional capacity, quality of life, mobility, muscle strength, goniometry, and
      pain. It appears to be a safe tool for accelerating recovery in THA patients.
      CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; NCT01491048.

PMID- 25856761
TI  - Definitive peritoneal drainage in the extremely low birth weight infant with
      spontaneous intestinal perforation: predictors and hospital outcomes.
AB  - OBJECTIVE: To identify characteristics associated with definitive peritoneal
      drainage (PD) in the extremely low birth weight infant diagnosed with spontaneous
      intestinal perforation (SIP). We also sought to determine whether patients
      requiring a second operation (salvage laparotomy) following PD are at increased
      risk of adverse hospital outcomes, including increased times to full enteral
      feedings and decreased 30-day survival. STUDY DESIGN: We performed a
      retrospective chart review of infants with a birth weight <1000 g who underwent
      PD for SIP at a single tertiary neonatal unit from 2003 to 2012. Infants with
      signs of necrotizing enterocolitis on abdominal plain films, including
      pneumatosis intestinalis, portal venous gas or fixed, dilated small loops of
      bowel were excluded from the study. Perinatal and perioperative data and short
      term neonatal outcomes prior to hospital discharge were collected. Comparison was
      made between two groups: infants treated with definitive PD vs infants requiring
      salvage laparotomy. Data were analyzed using independent samples t-test and
      Cochrane-Mantel-Haenszel. RESULT: Eighty-nine infants who fit all inclusion
      criteria were identified during the study period. PD was definitive in 67 (75.3%)
      patients. Patients who had definitive PD vs those who required salvage laparotomy
      were significantly more likely to present at a later day of life (9.6+/-5.3 vs
      5.6+/-2.7, P<0.0001) and to have a lower birth weight (724.6 g+/-132.5 vs 809.2
      g+/-143.1, P=0.02). The administration of indomethacin or ibuprofen prior to the
      diagnosis of SIP was also associated with definitive PD (74.6% vs 50%, P=0.03).
      Comparison of feeding outcomes revealed that the time to achieve full enteral
      feeds was significantly longer for those who underwent a salvage laparotomy
      (95.9+/-30.2 vs 60.4+/-30.4 days, P<0.005). Short-term survival (>30 days) was
      not significantly different between the two groups. CONCLUSION: PD was definitive
      therapy for the majority of neonates included in this study who were referred for
      surgical evaluation of SIP. Our data point to trends in being able to identify
      infants with SIP who are at risk for salvage laparotomy following PD, and thus,
      adverse nutritional outcomes. Larger, prospective studies are needed to further
      evaluate this specific patient population and identify those patients who are
      likely to succeed with PD following the diagnosis of SIP.

PMID- 25856762
TI  - Progress of PTSD symptoms following birth: a prospective study in mothers of high
      risk infants.
AB  - OBJECTIVE: To understand how postpartum posttraumatic stress disorder (PTSD)
      symptoms in mothers of high-risk infants progress and identify what factors
      predict postpartum PTSD. STUDY DESIGN: We prospectively obtained self-reported
      psychological data from neonatal intensive care unit discharged infants' mothers
      (NICU mothers) at the infants' corrected ages of 1 (T0), 3 (T1) and 12 months
      (T2) and mothers of healthy infants (controls). Maternal sociodemographic and
      infant-related factors were also investigated. RESULT: PTSD was present in 25 and
      9% of NICU mothers and controls, respectively. We identified four PTSD patterns:
      none, persistent, delayed and recovered. The postpartum PTSD course was
      associated with trait anxiety. Whether the infant was the first child who
      predicted PTSD at year 1 (adjusted odds ratio=7.62, 95% confidence interval=1.07
      to 54.52). CONCLUSION: Mothers of high-risk infants can develop early or late
      PTSD, and its course can be influenced by factors besides medical status. We
      therefore recommend regular screenings of postpartum PTSD.

PMID- 25856763
TI  - Mid-trimester amniotic fluid pro-inflammatory biomarkers predict the risk of
      spontaneous preterm delivery in twins: a retrospective cohort study.
AB  - OBJECTIVE: To evaluate the association between the concentrations of immune
      related proteins in mid-trimester amniotic fluid (AF) and the subsequent risk of
      spontaneous preterm delivery in twins. STUDY DESIGN: The study population
      consisted of consecutive women with a twin pregnancy who underwent clinically
      indicated genetic amniocentesis at 15 to 20 weeks, and had a subsequent
      spontaneous delivery in the early preterm period (<32 weeks (cases)) or at term
      (37 to 42 weeks (controls)). AF was analyzed for cytokines (interleukin (IL)
      1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13 and IL-15, interferon
      gamma, tumor necrosis factor-alpha), matrix metalloproteinases (MMP-1, MMP-2, MMP
      3, MMP-8, MMP-9 and MMP-12), and chemokines (complement factor-D/Adipsin, Serpin
      E1/PAI-1, Adiponectin/Acrp30, C-Reactive Protein, CCL2/MCP-1, Leptin, Resistin)
      using multiplex immunoassay kits. The association between AF protein levels and
      subsequent early preterm birth were examined. RESULT: A total of 96 sets of twins
      were enrolled, including 17 early preterm birth cases and 79 term controls. AF
      concentrations of IL-6, IL-8, MMP-3, MMP-8 and MMP-9, and CCL2/MCP-1 were
      significantly higher in cases than controls. Among these analytes, the
      combination of AF IL-8 and MMP-9 values had the highest predictive value for
      early preterm birth. The risk was 8% (10/132) for IL-8<1200 pg ml(-1) and MMP
      9<1000 pg ml(-1), 30% (15/50) for IL-8>1200 pg ml(-1) or MMP-9>1000 pg ml(-1),
      and 90% (9/10) for IL-8>1200 pg ml(-1) and MMP-9>1000 pg ml(-1) (P<0.001).
      CONCLUSION: High concentrations of IL-8 and MMP-9 in mid-trimester AF in twins
      predicted well the risk of early preterm birth.

PMID- 25856764
TI  - Predictors of successful closure of patent ductus arteriosus with indomethacin.
AB  - OBJECTIVE: To determine whether platelet counts can predict the likelihood of
      successful closure of patent ductus arteriosus (PDA) with indomethacin. STUDY
      DESIGN: This was a retrospective cohort study of infants <32 weeks' gestational
      age (GA) and birth weight <1500 g with PDA. Clinical characteristics between
      infants who achieved ductal closure with indomethacin and those who failed were
      compared. Multivariable logistic regression was used to identify predictors of
      successful ductal closure. RESULTS: In infants with hemodynamically significant
      PDA, older GA (odds ratio=1.54; 95% confidence interval: 1.12 to 2.13), male
      gender (odds ratio=3.02; 95% confidence interval: 1.08 to 8.49) and higher
      platelet count (odds ratio=1.5; 95% confidence interval: 1.04 to 2.17) prior to
      indomethacin treatment were associated with successful ductal closure with
      indomethacin. CONCLUSION: Older GA, male gender and higher platelet count at time
      of treatment of hemodynamically significant PDA are predictors of successful
      ductal closure with indomethacin.

PMID- 25856765
TI  - Update in hospice and palliative care.

PMID- 25856768
TI  - Older age and steroid use are associated with increasing polypharmacy and
      potential medication interactions among patients with inflammatory bowel disease.
AB  - BACKGROUND: Comorbidity and polypharmacy, more prevalent among older persons, may
      impact the treatment of patients with inflammatory bowel disease (IBD). The aims
      of this study were to assess the frequency of polypharmacy and medication
      interactions within a cohort of older patients with IBD and describe IBD
      treatment patterns. METHODS: Cohort study of 190 patients with IBD 65 years or
      older followed at a tertiary IBD referral center from 2006 to 2012. Data
      collected included demographics, IBD-specific characteristics including disease
      activity, and comorbidity. Medication histories were extracted from medical
      records, and data were used to classify polypharmacy, frequency, and severity of
      potential medication interactions and inappropriate medication use. RESULTS:
      Older patients with IBD were prescribed an average of 9 routine medications.
      Severe polypharmacy (>=10 routine medications) was present in 43.2% of studied
      patients and associated with increasing age, greater comorbidity, and steroid
      use. Overall, 73.7% of patients had at least 1 potential medication interaction,
      including 40% of patients with potential IBD medication-associated interactions.
      Chronic steroids were prescribed to 40% of the older patients including 24% who
      were in remission or with mild disease activity. Only 39.5% of patients were on
      immunomodulators and 21.1% on biologics. Approximately, 35% of patients were
      given at least 1 Beers inappropriate medication and almost 10% were receiving
      chronic narcotics. CONCLUSIONS: Older patients with IBD are at increased risk for
      severe polypharmacy and potential major medication interactions especially with
      increasing comorbidity and chronic steroid use. Steroid-maintenance therapies are
      prevalent among the older patients with IBD with lower utilization of steroid
      sparing regimens.

PMID- 25856767
TI  - A global and local desymmetrization approach to the synthesis of steroidal
      alkaloids: stereocontrolled total synthesis of paspaline.
AB  - A stereocontrolled total synthesis of the indole diterpenoid natural product
      paspaline is described. Key steps include a highly diastereoselective enzymatic
      desymmetrization, substrate-directed epoxidation, Ireland-Claisen rearrangement,
      and diastereotopic group selective C-H acetoxylation to assemble the target with
      excellent stereofidelity. The route and results described herein outline
      complementary conceptual disconnections in the arena of steroid natural product
      synthesis. 

PMID- 25856769
TI  - Efficacy and Safety of Natalizumab and Vedolizumab for the Management of Crohn's
      Disease: A Systematic Review and Meta-analysis.
AB  - BACKGROUND: We assessed the risk-benefit profile of anti-alpha4-integrins,
      natalizumab (NAT), and vedolizumab (VEDO), in Crohn's disease through a
      systematic review and meta-analysis of randomized controlled trials. METHODS: We
      searched multiple electronic databases through July 2014 and identified 8
      randomized controlled trials in adults with Crohn's disease comparing NAT (5
      trials) or VEDO (3 trials) with placebo. Efficacy outcomes were induction of
      remission, response, and improvement in quality of life; safety outcomes were
      serious adverse events, infusion reactions, infections, and treatment
      discontinuation. We performed subgroup analysis based on anti-tumor necrosis
      factor (TNF)-alpha exposure and estimated summary relative risk (RR) or mean
      difference, with 95% confidence intervals (CIs). RESULTS: Anti-alpha4-integrins
      were superior to placebo for induction of remission (RR, 0.87; 95% CI, 0.84
      0.91), with similar estimates for NAT (RR, 0.86; 95% CI, 0.80-0.93) and VEDO (RR,
      0.87; 95% CI, 0.79-0.95). Both NAT and VEDO were equally efficacious for anti-TNF
      naive (NAT: RR, 0.87; 95% CI, 0.75-1.00; VEDO: RR, 0.86; 95% CI, 0.79-0.94) and
      anti-TNF-exposed patients (NAT: RR, 0.86; 95% CI, 0.76-0.99; VEDO: RR, 0.89; 95%
      CI, 0.78-1.01). Anti-alpha4-integrins were effective in inducing clinical
      response and improving quality of life, with no significant difference between
      NAT and VEDO. Rates of serious adverse events, infusion reactions, infections,
      and treatment discontinuation were similar for NAT and VEDO. No cases of
      progressive multifocal leukoencephalopathy have been observed with VEDO to date.
      CONCLUSIONS: NAT and VEDO are effective in inducing remission and response in
      patients with Crohn's disease, with similar efficacy in anti-TNF-naive and anti
      TNF-exposed patients.

PMID- 25856771
TI  - Reply to can fecal calprotection identify postoperative recurrence of Crohn's
      disease?

PMID- 25856770
TI  - G Protein-coupled pH-sensing Receptor OGR1 Is a Regulator of Intestinal
      Inflammation.
AB  - BACKGROUND: A novel family of proton-sensing G protein-coupled receptors,
      including OGR1, GPR4, and TDAG8, was identified to be important for physiological
      pH homeostasis and inflammation. Thus, we determined the function of proton
      sensing OGR1 in the intestinal mucosa. MTEHODS: OGR1 expression in colonic
      tissues was investigated in controls and patients with IBD. Expression of OGR1
      upon cell activation was studied in the Mono Mac 6 (MM6) cell line and primary
      human and murine monocytes by real-time PCR. Ogr1 knockout mice were crossbred
      with Il-10 deficient mice and studied for more than 200 days. Microarray
      profiling was performed using Ogr1 and Ogr1 (WT) residential peritoneal
      macrophages. RESULTS: Patients with IBD expressed higher levels of OGR1 in the
      mucosa than non-IBD controls. Treatment of MM6 cells with TNF, led to significant
      upregulation of OGR1 expression, which could be reversed by the presence of NF
      kappaB inhibitors. Kaplan-Meier survival analysis showed a significantly delayed
      onset and progression of rectal prolapse in female Ogr1/Il-10 mice. These mice
      displayed significantly less rectal prolapses. Upregulation of gene expression,
      mediated by OGR1, in response to extracellular acidification in mouse macrophages
      was enriched for inflammation and immune response, actin cytoskeleton, and cell
      adhesion gene pathways. CONCLUSIONS: OGR1 expression is induced in cells of human
      macrophage lineage and primary human monocytes by TNF. NF-kappaB inhibition
      reverses the induction of OGR1 expression by TNF. OGR1 deficiency protects from
      spontaneous inflammation in the Il-10 knockout model. Our data indicate a
      pathophysiological role for pH-sensing receptor OGR1 during the pathogenesis of
      mucosal inflammation.

PMID- 25856772
TI  - Single-source precursors for alloyed gold-silver nanocrystals - a molecular
      metallurgy approach.
AB  - Multiple silver(I)-aurates(I) have been prepared by salt metathesis reactions
      that act as efficient single-source precursors to colloidal gold silver alloys
      with the highest possible atom economy in the chemical synthesis of
      nanostructures. The CF3 group present on the Au cation acts as an in situ
      reducing agent and can be converted into CO ligands by simple hydrolysis. This
      ligand-mediated activation and subsequent decomposition of metal-organic
      precursors impose a molecular control over the nucleation process, producing
      homogeneously alloyed (Ag-Au) nanoparticles with an atomic Au:Ag ratio of 1:1.
      The concept also works for the Au-Cu system and acts as a pointer to replace Au
      (Ag) with less expensive (Cu) metals. 

PMID- 25856766
TI  - Central pathways causing fatigue in neuro-inflammatory and autoimmune illnesses.
AB  - BACKGROUND: The genesis of severe fatigue and disability in people following
      acute pathogen invasion involves the activation of Toll-like receptors followed
      by the upregulation of proinflammatory cytokines and the activation of microglia
      and astrocytes. Many patients suffering from neuroinflammatory and autoimmune
      diseases, such as multiple sclerosis, Parkinson's disease and systemic lupus
      erythematosus, also commonly suffer from severe disabling fatigue. Such patients
      also present with chronic peripheral immune activation and systemic inflammation
      in the guise of elevated proinflammtory cytokines, oxidative stress and activated
      Toll-like receptors. This is also true of many patients presenting with severe,
      apparently idiopathic, fatigue accompanied by profound levels of physical and
      cognitive disability often afforded the non-specific diagnosis of chronic fatigue
      syndrome. DISCUSSION: Multiple lines of evidence demonstrate a positive
      association between the degree of peripheral immune activation, inflammation and
      oxidative stress, gray matter atrophy, glucose hypometabolism and cerebral
      hypoperfusion in illness, such as multiple sclerosis, Parkinson's disease and
      chronic fatigue syndrome. Most, if not all, of these abnormalities can be
      explained by a reduction in the numbers and function of astrocytes secondary to
      peripheral immune activation and inflammation. This is also true of the
      widespread mitochondrial dysfunction seen in otherwise normal tissue in
      neuroinflammatory, neurodegenerative and autoimmune diseases and in many patients
      with disabling, apparently idiopathic, fatigue. Given the strong association
      between peripheral immune activation and neuroinflammation with the genesis of
      fatigue the latter group of patients should be examined using FLAIR magnetic
      resonance imaging (MRI) and tested for the presence of peripheral immune
      activation. SUMMARY: It is concluded that peripheral inflammation and immune
      activation, together with the subsequent activation of glial cells and
      mitochondrial damage, likely account for the severe levels of intractable fatigue
      and disability seen in many patients with neuroimmune and autoimmune
      diseases.This would also appear to be the case for many patients afforded a
      diagnosis of Chronic Fatigue Syndrome.

PMID- 25856774
TI  - Multiphase chemistry at the atmosphere-biosphere interface influencing climate
      and public health in the anthropocene.

PMID- 25856773
TI  - Dominant Alcohol-Protein Interaction via Hydration-Enabled Enthalpy-Driven
      Binding Mechanism.
AB  - Water plays an important role in weak associations of small drug molecules with
      proteins. Intense focus has been on binding-induced structural changes in the
      water network surrounding protein binding sites, especially their contributions
      to binding thermodynamics. However, water is also tightly coupled to protein
      conformations and dynamics, and so far little is known about the influence of
      water-protein interactions on ligand binding. Alcohols are a type of low-affinity
      drugs, and it remains unclear how water affects alcohol-protein interactions.
      Here, we present alcohol adsorption isotherms under controlled protein hydration
      using in situ NMR detection. As functions of hydration level, Gibbs free energy,
      enthalpy, and entropy of binding were determined from the temperature dependence
      of isotherms. Two types of alcohol binding were found. The dominant type is low
      affinity nonspecific binding, which is strongly dependent on temperature and the
      level of hydration. At low hydration levels, this nonspecific binding only occurs
      above a threshold of alcohol vapor pressure. An increased hydration level reduces
      this threshold, with it finally disappearing at a hydration level of h ~ 0.2 (g
      water/g protein), gradually shifting alcohol binding from an entropy-driven to an
      enthalpy-driven process. Water at charged and polar groups on the protein surface
      was found to be particularly important in enabling this binding. Although further
      increase in hydration has smaller effects on the changes of binding enthalpy and
      entropy, it results in a significant negative change in Gibbs free energy due to
      unmatched enthalpy-entropy compensation. These results show the crucial role of
      water-protein interplay in alcohol binding. 

PMID- 25856775
TI  - Hearing Care for Older Adults: Beyond the Audiology Clinic.
AB  - Purpose: The purpose of this article was to highlight the importance of hearing
      health care beyond the clinic for older people with impaired hearing. Method: To
      emphasize factors affecting the success of audiologic rehabilitation for older
      people and to describe practical clinical and community-based strategies to
      promote successful hearing health care. Result: Older people are not always aware
      of the extent of their hearing loss, they may not always expect to benefit from
      using a hearing aid, and they often have low self-efficacy for managing to learn
      to use hearing aids. Increased knowledge and support from other health
      professionals, family caregivers and significant others could optimize older
      peoples' participation in everyday activities. Conclusion: Further work is needed
      to develop new interventions for older people with impaired hearing and to
      increase collaboration with general practitioners as well as other health-care
      professionals.

PMID- 25856776
TI  - Anti-programmed cell death protein-1/ligand-1 therapy in different cancers.
AB  - Immunologic checkpoint blockade with antibodies against the programmed cell death
      protein-1 (PD-1) or its ligand (PD-L1) is an effective method for reversing
      cancer immunosuppression and thereby promoting immune responses against several
      cancer types. Anti-PD-1 and anti-PD-L1 antibodies have resulted in long-term
      responses with minimal side effects in significant numbers of patients with
      melanoma, lung, kidney, bladder and triple-negative breast cancer, as well as in
      chemotherapy-refractory Hodgkin disease. There is already evidence from at least
      one randomised trial that anti-PD-1 therapy is superior to chemotherapy in the
      treatment of patients with metastatic melanoma, and two anti-PD-1 antibodies,
      pembrolizumab and nivolumab, have been approved by the US Food and Drug
      Administration for the treatment of patients previously treated for metastatic
      melanoma. It is anticipated that approvals by drug regulatory bodies will be
      forthcoming in several cancers in the next months. 

PMID- 25856778
TI  - Antiphospholipid Antibodies Alter Cell-Death-Regulating Lipid Metabolites in
      First and Third Trimester Human Placentae.
AB  - PROBLEM: Antiphospholipid antibodies (aPL) are maternal autoantibodies that
      increase the risk of a woman developing preeclampsia 10-fold. aPL are
      internalized into the syncytiotrophoblast and increase extrusion of necrotic
      trophoblast debris into the maternal blood. This necrotic trophoblast debris may
      trigger endothelial cell dysfunction contributing to the pathogenesis of
      preeclampsia. We hypothesize that aPL directly affect placental metabolism,
      leading to increased syncytiotrophoblast death. METHODS OF STUDY: First and third
      trimester human placental explants were cultured with aPL, a control antibody, or
      media only, and placental conditioned culture media was examined by mass
      spectroscopy. Molecular targets of interest were investigated using qRTPCR and
      immunohistochemistry. RESULTS: The levels of 79 and 132 metabolites,
      respectively, were altered due to the treatment of first and third trimester
      placental explants with aPL. These included ceramides and diacylglycerols, which
      play important roles in cell death regulatory pathways. Antiphospholipid
      antibodies also decreased the expression of protein kinase C-epsilon (PRKCE) in
      placental explants, possibly due to the disrupted balance between ceramides and
      diacylglycerols caused by aPL. CONCLUSION: One mechanism by which aPL cause
      aberrant cell death in the syncytiotrophoblast in the first and third trimester
      is by disruption of placental lipid signaling and decreased expression of PRKCE.

PMID- 25856781
TI  - Epitaxial CrN thin films with high thermoelectric figure of merit.
AB  - A large enhancement of the thermoelectric figure of merit is reported in single
      crystalline films of CrN. The mechanism of the reduction of the lattice thermal
      conductivity in cubic CrN is similar to the resonant bonding in IV-VI compounds.
      Therefore, useful ideas from classic thermo-electrics can be applied to tune
      functionalities in transition metal nitrides and oxides. 

PMID- 25856777
TI  - Somatic Cough Syndrome (Previously Referred to as Psychogenic Cough) and Tic
      Cough (Previously Referred to as Habit Cough) in Adults and Children: CHEST
      Guideline and Expert Panel Report.
AB  - BACKGROUND: We conducted a systematic review on the management of psychogenic
      cough, habit cough, and tic cough to update the recommendations and suggestions
      of the 2006 guideline on this topic. METHODS: We followed the American College of
      Chest Physicians (CHEST) methodologic guidelines and the Grading of
      Recommendations, Assessment, Development, and Evaluation framework. The Expert
      Cough Panel based their recommendations on data from the systematic review,
      patients' values and preferences, and the clinical context. Final grading was
      reached by consensus according to Delphi methodology. RESULTS: The results of the
      systematic review revealed only low-quality evidence to support how to define or
      diagnose psychogenic or habit cough with no validated diagnostic criteria. With
      respect to treatment, low-quality evidence allowed the committee to only suggest
      therapy for children believed to have psychogenic cough. Such therapy might
      consist of nonpharmacologic trials of hypnosis or suggestion therapy, or
      combinations of reassurance, counseling, and referral to a psychologist,
      psychotherapy, and appropriate psychotropic medications. Based on multiple
      resources and contemporary psychologic, psychiatric, and neurologic criteria
      (Diagnostic and Statistical Manual of Mental Disorders, 5th edition and tic
      disorder guidelines), the committee suggests that the terms psychogenic and habit
      cough are out of date and inaccurate. CONCLUSIONS: Compared with the 2006 CHEST
      Cough Guidelines, the major change in suggestions is that the terms psychogenic
      and habit cough be abandoned in favor of somatic cough syndrome and tic cough,
      respectively, even though the evidence to do so at this time is of low quality.

PMID- 25856782
TI  - Cobalt(II) catalyzed C(sp)-H bond functionalization of alkynes with phenyl
      hydrazines: facile access to diaryl 1,2-diketones.
AB  - A cobalt acetylacetonate catalyzed oxidative diketonation of alkynes via C(sp)-H
      bond functionalization has been described. The reaction involves a free-radical
      mechanism, wherein the phenyl radical formed from phenyl hydrazine couples with
      Co(II) activated alkyne to produce 1,2-diketones. The reaction proceeds at room
      temperature in DMF with the use of Ag2O/air as the oxidizing system. The utility
      of the protocol for the synthesis of a series of imidazoles including a potent
      platelet aggregation inhibitor trifenagrel has been demonstrated.

PMID- 25856783
TI  - Assessing Prolongation of the Heart Rate Corrected QT Interval in Users of
      Tricyclic Antidepressants: Advice to Use Fridericia Rather Than Bazett's
      Correction.
AB  - A prolonged heart rate corrected QT interval (QTc) increases the risk of sudden
      cardiac death. Some methods of heart rate correction (notably Bazett)
      overestimate QTc in people with high heart rates. Studies suggest that tricyclic
      antidepressants (TCAs) can prolong the QTc and increase heart rate. Therefore, we
      aimed to study whether TCA-induced QTc prolongation is a false-positive
      observation due to overestimation at high heart rates. For this, we included
      12,734 participants from the prospective population-based Rotterdam Study, with a
      total of 27,068 electrocardiograms (ECGs), of which, 331 during TCA use.
      Associations between use of TCAs, QTc, and heart rate were studied with linear
      repeated measurement analyses. QT was corrected for heart rate according to
      Bazett (QTcBazett), Fridericia (QTcFridericia), or a correction based on
      regression coefficients obtained from the Rotterdam Study data (QTcStatistical).
      On ECGs recorded during TCA use, QTcBazett was 6.5 milliseconds (95% confidence
      interval, 4.0-9.0) longer, and heart rate was 5.8 beats per minute (95%
      confidence interval, 4.7-6.9) faster than during nonuse. QTcFridericia and
      QTcStatistical were not statistically significantly longer during TCA use than
      during nonuse. Furthermore, QTcBazett was similar for ECGs recorded during TCA
      use and nonuse after statistical adjustment for heart rate. According to our
      results, TCA use does not seem to be associated with QTc prolongation. Therefore,
      the current advice of regulatory authorities to restrict the use of these drugs
      and to do regular checkups of the QTc may need to be revised. Other formulas,
      like Fridericia's, might be preferred. 

PMID- 25856784
TI  - Agomelatine as a novel treatment option in panic disorder, results from an 8-week
      open-label trial.

PMID- 25856785
TI  - Visit-to-visit variability and seasonal variation in blood pressure: Combination
      of Antihypertensive Therapy in the Elderly, Multicenter Investigation (CAMUI)
      Trial subanalysis.
AB  - BACKGROUND: Combination antihypertensive therapy with an angiotensin receptor
      blocker (ARB) and a calcium channel blocker (CCB) or diuretics is common. This
      subanalysis investigated blood pressure (BP) variability in patients receiving
      ARB-based combination therapy. METHODS: In a prospective, randomized, open-label
      trial, hypertensive outpatients (>=65 years) who did not achieve their target BP
      with ARB monotherapy switched to losartan 50 mg/hydrochlorothiazide 12.5 mg (ARB
      + D) or ARB plus amlodipine 5 mg (ARB + C) for 12 months. Clinic BP and heart
      rate (HR), measured every 3 months, visit-to-visit variability and seasonal
      variation were evaluated. RESULTS: No significant between-group differences in
      average, maximum, or minimum systolic or diastolic BP, or HR, were found. Visit
      to-visit BP variability (systolic) was significantly higher in the ARB + D group
      than in the ARB + C group. When each group was subdivided into two seasonal
      groups (summer and winter), no significant between-group differences in BP were
      found. Multivariate regression analyses showed a tendency toward negative
      correlation between outdoor temperature and urinary albumin:creatinine ratio and
      estimated glomerular filtration rate at 12 months in the ARB + D group.
      CONCLUSION: Combination therapy with an ARB plus a CCB may be preferable to that
      with an ARB plus diuretics for decreasing BP variability. As for seasonal
      variability, both treatments can be used safely regardless of season.

PMID- 25856786
TI  - Cognitive function in Chinese prostate cancer patients on androgen-deprivation
      therapy: A cross-sectional study.
AB  - AIMS: Androgen-deprivation therapy (ADT) is a main treatment option for patients
      with prostate cancer (PCa), but its effect on cognition remains unclear. The
      primary purpose of this cross-sectional case-control study was to evaluate the
      effects of ADT on cognition in Chinese PCa patients. METHODS: Participants
      included PCa patients who had undergone ADT (ADT group, n = 33) and patients who
      did not undergo ADT (non-ADT group, n = 32), as well as age- and education
      matched healthy controls (HC group, n = 35). All participants were examined using
      the neuropsychological battery aimed at assessing several cognitive domains
      including attention, memory and information processing performance. RESULTS: The
      ADT group obtained significantly worse scores than the non-ADT and HC groups in
      the following neuropsychological tests: Recognition (P < 0.01), WAIS Digit Span
      forward (P < 0.05), Trailmaking B (P < 0.01) and Stroop Interference test (P <
      0.01). No significant difference was found between the non-ADT and HC groups (P >
      0.05). CONCLUSIONS: Chinese PCa patients receiving ADT showed cognitive
      impairments in several domains including memory, attention and information
      processing performance.

PMID- 25856787
TI  - Type 2 diabetes-associated carotid plaque burden is increased in patients with
      retinopathy compared to those without retinopathy.
AB  - BACKGROUND: Cardiovascular disease (CVD) is the leading cause of mortality among
      subjects with type 2 diabetes (T2D), and diabetic retinopathy (DR) has been
      associated with an increased risk for CVD. The present study was designed to test
      the concept that T2D patients with DR, but without previous cardiovascular (CV)
      events and with normal renal function, have an increased atherosclerotic burden
      compared with patients without DR. METHODS: A cross-sectional study was performed
      using patients with normal renal function (estimated glomerular filtration rate
      (eGFR) >60 ml/min) and without previous CV events. A total of 312 patients (men,
      51%; mean age, 57 yrs; age range 40-75 yrs) were included in the study; 153 (49%)
      of the patients had DR. B-mode carotid ultrasound imaging was performed for all
      of the study subjects to measure the carotid intima-media thickness (cIMT) and
      carotid plaques in the common carotid artery (CCA), bifurcation and internal
      carotid artery (ICA). RESULTS: The percentage of carotid plaques in T2D patients
      with DR was higher than in T2D patients without DR (68% vs. 52.2%, p = 0.0045),
      and patients with DR had a higher prevalence of >=2 carotid plaques (44.4% vs.
      21.4%; p < 0.0001). No differences were observed in the cIMT measured at
      different carotid regions between the patients with or without DR. Using
      multivariate logistic regression (adjustment for major risk factors for
      atherosclerosis), DR was independently associated with mean-internal cIMT (p =
      0.0176), with the presence of carotid plaques (p = 0.0366) and with carotid
      plaque burden (>=2 plaques; p < 0.0001). CONCLUSIONS: The present study shows
      that DR in T2D patients without CVD and with normal renal function is associated
      with a higher atherosclerotic burden (presence and number of plaques) in the
      carotid arteries. These patients may be at a higher risk for future CV events;
      therefore, an ultrasound examination of the carotid arteries should be considered
      in patients with DR for more careful and individualised CV assessment and follow
      up.

PMID- 25856790
TI  - Plasma metabolic profiling after cortical spreading depression in a transgenic
      mouse model of hemiplegic migraine by capillary electrophoresis--mass
      spectrometry.
AB  - Migraine is a common brain disorder characterized by recurrent attacks of severe
      headaches and other neurological symptoms. In one-third of patients headaches are
      accompanied by auras, which consist of transient visual and sensory disturbances,
      believed to be caused by cortical spreading depression (CSD). CSD is
      characterized by a wave of neuronal and glial depolarization with concomitant
      changes in metabolite concentrations in the brain and cerebrospinal fluid. It
      remains unknown whether CSD-induced brain metabolic changes can be captured
      outside the central nervous system, i.e., in peripheral fluids. This study
      investigated plasma metabolic changes in transgenic mice that harbor a gene
      mutation in voltage-gated CaV2.1 Ca(2+) channels previously identified in
      patients with familial hemiplegic migraine, a subtype of migraine with auras. The
      use of a mouse model allows investigation of molecular changes occurring shortly
      after CSD, which is notoriously difficult in patients. Capillary electrophoresis 
      mass spectrometry was used for the analysis of plasma samples to obtain, for the
      first time, a comprehensive view of molecular changes immediately after
      experimentally induced CSD. Multivariate data analysis showed a clear distinction
      between profiles of transgenic and wild-type animals after CSD. Two metabolites
      considered important for this discrimination were tentatively identified as being
      lysine and its by-product pipecolic acid with additional evidence provided by
      hydrophilic interaction chromatography combined with tandem mass spectrometry.
      The changed metabolites suggest a compensatory increase in GABAergic
      neurotransmission upon enhanced excitatory neurotransmission. These results show
      that CSD induces metabolic remodeling in transgenic migraine mice that can be
      captured and measured in plasma. 

PMID- 25856789
TI  - Emergency department visits for non-life-threatening conditions: evolution over
      13 years in a Swiss urban teaching hospital.
AB  - INTRODUCTION: A large proportion of visits to our Emergency Department (ED) are
      for non-life-threatening conditions. We investigated whether patients'
      characteristics and reasons for consultation had changed over 13 years. METHODS:
      Consecutive adult patients with non-life-threatening conditions at triage were
      included in the spring of 2000 and in the summer of 2013. In both years patients
      completed a similar questionnaire, which addressed their reasons for consultation
      and any previous consultation with a general practitioner (GP). RESULTS: We
      included 581 patients in 2013 vs 516 in 2000, with a mean age of 44.5 years vs
      46.4 years (p=0.128). Of these patients, 54.0% vs 57.0% were male (p=0.329),
      55.5% vs 58.7% were Swiss (p=0.282), 76.4% were registered with a GP in both
      periods, but self-referral increased from 52.0% to 68.8% (p<0.001); 57.7% vs.,
      58.3% consulted during out-of- hours (p=0.821). Trauma-related visits decreased
      from 34.2% to 23.7% (p<0.001). Consultations within 12 hours of onset of symptoms
      dropped from 54.5% to 30.9%, and delays of >=1 week increased from 14.3% to 26.9%
      (p<0.001). The primary motive for self-referral remained unawareness of an
      alternative, followed in 2013 by dissatisfaction with the GP's treatment or
      appointment. Patients who believed that their health problem would not require
      hospitalisation increased from 52.8% to 74.2% and those who were actually
      hospitalised decreased from 24.9% to 13.9% (all p<0.001). CONCLUSION: The number
      of visits for non-life-threatening consultations continue to increase. Our ED is
      used by a large proportion of patients as a convenient alternative source of
      primary care.

PMID- 25856792
TI  - Direct Immersion Solid-Phase Microextraction with Matrix-Compatible Fiber Coating
      for Multiresidue Pesticide Analysis of Grapes by Gas Chromatography-Time-of
      Flight Mass Spectrometry (DI-SPME-GC-ToFMS).
AB  - A fast and sensitive direct immersion-solid-phase microextraction-gas
      chromatography-time-of-flight mass spectrometry (DI-SPME-GC-ToFMS) method for the
      determination of multiresidue pesticides in grapes employing a PDMS-modified
      PDMS/DVB coating was developed utilizing multivariate approaches for optimization
      of the most important factors affecting SPME performance. A comprehensive
      investigation of appropriate internal standards using a bottom-up approach led to
      the selection of suitable compounds that adequately covered a range of 40
      pesticides pertaining to various classes. The validated method yielded good
      accuracy, precision, and sensitivity and has been successfully applied to the
      analysis of commercial samples. With regard to the limitations of the proposed
      method, the DI-SPME method did not provide a satisfactory performance toward more
      polar pesticides (e.g., acephate, omethoate, dimethoate) and highly hydrophobic
      pesticides, such as pyrethroids. Despite the challenges and limitations
      encountered by this method, the practical aspects of the PDMS-modified coating
      demonstrated here create new opportunities for SPME applied in food analysis. 

PMID- 25856791
TI  - Effectiveness of community-based integrated care in frail COPD patients: a
      randomised controlled trial.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) generates a high burden
      on health care, and hospital admissions represent a substantial proportion of the
      overall costs of the disease. Integrated care (IC) has shown efficacy to reduce
      hospitalisations in COPD patients at a pilot level. Deployment strategies for IC
      services require assessment of effectiveness at the health care system level.
      AIMS: The aim of this study was to explore the effectiveness of a community-based
      IC service in preventing hospitalisations and emergency department (ED) visits in
      stable frail COPD patients. METHODS: From April to December 2005, 155 frail
      community-dwelling COPD patients were randomly allocated either to IC (n=76, age
      73 (8) years, forced expiratory volume during the first second, FEV1 41(19) %
      predicted) or usual care (n=84, age 75(9) years, FEV1 44 (20) % predicted) and
      followed up for 12 months. The IC intervention consisted of the following: (a)
      patient's empowerment for self-management; (b) an individualised care plan; (c)
      access to a call centre; and (d) coordination between the levels of care.
      Thereafter, hospital admissions, ED visits and mortality were monitored for 6
      years. RESULTS: IC enhanced self-management (P=0.02), reduced anxiety-depression
      (P=0.001) and improved health-related quality of life (P=0.02). IC reduced both
      ED visits (P=0.02) and mortality (P=0.03) but not hospital admission. No
      differences between the two groups were seen after 6 years. CONCLUSION: The
      intervention improved clinical outcomes including survival and decreased the ED
      visits, but it did not reduce hospital admissions. The study facilitated the
      identification of two key requirements for adoption of IC services in the
      community: appropriate risk stratification of patients, and preparation of the
      community-based work force.

PMID- 25856793
TI  - pH-Driven Ordering Transitions in Liquid Crystal Induced by Conformational
      Changes of Cardiolipin.
AB  - We report an investigation of interfacial phenomena occurring at aqueous-liquid
      crystal (LC) interfaces that triggers an orientational ordering transition of the
      LC in the presence of cardiolipin (CL) by varying pH, salt concentration and
      valence. In particular, the effects of three different conformational isomeric
      forms of the CL are observed to cause the response of the LC ordering to vary
      significantly from one to another at those interfaces. An ordering transition of
      the LC was observed when the CL is mostly in undissociated (at pH 2) and/or in
      bicyclic (at pH 4) conformation in which LC shows changes in the optical
      appearance from bright to dark. By contrast, no change in the optical appearance
      of the LC was observed when the pH of the system increases to 8 or higher in
      which the CL mostly exists in the open conformation. Fluorescence microscopy
      measurements further suggest that pH-dependent conformational forms of the CL
      have different ability to self-assemble (thus different packing efficiency) at
      aqueous-LC interfaces leading to dissimilar orientational behavior of the LC.
      Specifically, we found that change in headgroup-headgroup repulsion of the
      central phosphatidyl groups of the CL plays a key role in tuning the lipid
      packing efficiency and thus responses to interfacial phenomena. Orientational
      ordering transition of the LC was also observed as a function of increasing the
      ionic strength (buffer capacity) and strongly influenced in the presence of mono
      and divalent cations. Langmuir-Blodgett (LB) and polarization modulation infrared
      reflection absorption spectroscopy (PM-IRRAS) measurements provide further
      insight in modulation of the lipid packing efficiency and alkyl chain
      conformation of the CL at different pH and ionic conditions. Overall, the results
      presented in this paper establish that LCs offer a promising approach to
      differentiate different conformations (label free detection) of the CL through
      ordering transition of the LC at aqueous-LC interfaces. 

PMID- 25856794
TI  - E-cigarettes: methodological and ideological issues and research priorities.
AB  - Cigarette combustion, rather than either tobacco or nicotine, is the cause of a
      public health disaster. Fortunately, several new technologies that vaporize
      nicotine or tobacco, and may make cigarettes obsolete, have recently appeared.
      Research priorities include the effects of vaporizers on smoking cessation and
      initiation, their safety and toxicity, use by non-smokers, dual use of vaporizers
      and cigarettes, passive vaping, renormalization of smoking, and the development
      of messages that effectively communicate the continuum of risk for tobacco and
      nicotine products. A major difficulty is that we are chasing a moving target. New
      products constantly appear, and research results are often obsolete by the time
      they are published. Vaporizers do not need to be safe, only safer than
      cigarettes. However, harm reduction principles are often misunderstood or
      rejected. In the context of a fierce ideological debate, and major investments by
      the tobacco industry, it is crucial that independent researchers provide
      regulators and the public with evidence-based guidance. The methodological and
      ideological hurdles on this path are discussed in this commentary. 

PMID- 25856796
TI  - Meeting the Hearing Health Care Needs of the Oldest Older Adult.
AB  - PURPOSE: The purpose of this article is to provide an overview of the auditory
      needs of and approaches to management of the oldest older adult. METHOD: This
      article is an overview of principles of geriatric care and implications of
      untreated hearing loss for function, management, and care of the oldest older
      adult. CONCLUSIONS: Person-centered care is at the heart of health care delivery
      to the oldest older adult, who typically suffers from multimorbidity. Given the
      high prevalence of moderate to severe hearing loss in this cohort and the
      functional limitations of untreated hearing loss, audiologists must become
      proactive in educating stakeholders on the importance of identifying and
      referring the oldest older adult for management of hearing health care needs.
      Audiologists have an integral role to play in collaborating with health care
      professionals in optimizing health care for the oldest older adult.

PMID- 25856795
TI  - Acacetin inhibits expression of matrix metalloproteinases via a MAPK-dependent
      mechanism in fibroblast-like synoviocytes.
AB  - It is well known that rheumatoid arthritis (RA) is an autoimmune joint disease in
      which fibroblast-like synoviocytes (FLSs) play a pivotal role. In this study, we
      investigated the anti-arthritic properties of acacetin in FLSs. The expression of
      matrix metalloproteinase (MMP)-1, MMP-3 and MMP-13 were investigated by
      quantitative RT-PCR and western blot at gene and protein levels. At the same
      time, the phosphorylation of mitogen-activated protein kinases (MAPK) was
      investigated. The DNA-binding activity of NF-kappaB was investigated by
      electrophoretic mobility shift assay. We found that acacetin inhibits p38 and JNK
      phosphorylation and reduces MMP-1, MMP-3 and MMP-13 expression in interleukin
      1beta-induced FLSs. Our results suggest that acacetin has antiarthritic effects
      in FLSs. Thus, acacetin should be further studied for the treatment of arthritis.

PMID- 25856797
TI  - One-dimension-based spatially ordered architectures for solar energy conversion.
AB  - The severe consequences of fossil fuel consumption have resulted in a need for
      alternative sustainable sources of energy. Conversion and storage of solar energy
      via a renewable method, such as photocatalysis, holds great promise as such an
      alternative. One-dimensional (1D) nanostructures have gained attention in solar
      energy conversion because they have a long axis to absorb incident sunlight yet a
      short radial distance for separation of photogenerated charge carriers. In
      particular, well-ordered spatially high dimensional architectures based on 1D
      nanostructures with well-defined facets or anisotropic shapes offer an exciting
      opportunity for bridging the gap between 1D nanostructures and the micro and
      macro world, providing a platform for integration of nanostructures on a larger
      and more manageable scale into high-performance solar energy conversion
      applications. In this review, we focus on the progress of photocatalytic solar
      energy conversion over controlled one-dimension-based spatially ordered
      architecture hybrids. Assembly and classification of these novel architectures
      are summarized, and we discuss the opportunity and future direction of
      integration of 1D materials into high-dimensional, spatially organized
      architectures, with a perspective toward improved collective performance in
      various artificial photoredox applications. 

PMID- 25856798
TI  - Anticardiolipin Antibodies in Children with Helicobacter pylori Infection.
AB  - BACKGROUND: Anticardiolipin (aCL) antibodies are associated with thrombosis and
      have an important role in the etiology of diseases such as stroke and myocardial
      infarction whose etiologies were based on thrombosis. H. pylori has been proposed
      to be responsible for the pathophysiology of some diseases including stroke,
      myocardial infarction, thrombosis, and autoimmune diseases. From this point of
      view, we hypothesized a possible relationship between H. pylori infection and aCL
      antibodies and initially aimed to determine the prevalence of aCL antibody
      positivity in children with H. pylori infection. MATERIALS AND METHODS:
      Anticardiolipin antibodies were studied in 84 patients before and after
      eradication therapy and in a control group including 40 children. RESULTS: The
      pretreatment aCL IgA (median 12.78 APL/mL), aCL IgM (median 21.60 MPL/mL), and
      aCL IgG antibody levels (median 14.22 GPL/mL) were significantly higher than
      those of post-treatment results (median 5.38 APL/mL, 7.02 MPL/mL, and 6.64
      GPL/mL, respectively) and controls (median 5.90 APL/mL, 4.80 MPL/mL, and 4.81
      GPL/mL, respectively). Anticardiolipin antibodies revealed no significant
      differences between the study group after therapy and the control group.
      CONCLUSIONS: In our particular experience, H. pylori can cause aCL antibody
      positivity in children and eradication of H. pylori provides the disappearance of
      these antibodies.

PMID- 25856799
TI  - Biochar from commercially cultivated seaweed for soil amelioration.
AB  - Seaweed cultivation is a high growth industry that is primarily targeted at human
      food and hydrocolloid markets. However, seaweed biomass also offers a feedstock
      for the production of nutrient-rich biochar for soil amelioration. We provide the
      first data of biochar yield and characteristics from intensively cultivated
      seaweeds (Saccharina, Undaria and Sargassum--brown seaweeds, and Gracilaria,
      Kappaphycus and Eucheuma--red seaweeds). While there is some variability in
      biochar properties as a function of the origin of seaweed, there are several
      defining and consistent characteristics of seaweed biochar, in particular a
      relatively low C content and surface area but high yield, essential trace
      elements (N, P and K) and exchangeable cations (particularly K). The pH of
      seaweed biochar ranges from neutral (7) to alkaline (11), allowing for broad
      spectrum applications in diverse soil types. We find that seaweed biochar is a
      unique material for soil amelioration that is consistently different to biochar
      derived from ligno-cellulosic feedstock. Blending of seaweed and ligno-cellulosic
      biochar could provide a soil ameliorant that combines a high fixed C content with
      a mineral-rich substrate to enhance crop productivity.

PMID- 25856801
TI  - Biomechanical and bioactivity concepts of polyetheretherketone composites for use
      in orthopedic implants-a review.
AB  - The use of polyetheretherketone (PEEK) composites in the trauma plating system,
      total replacement implants, and tissue scaffolds has found great interest among
      researchers. In recent years (2008 afterward), this type of composites has been
      examined for suitability as substitute material over stainless steel, titanium
      alloys, ultra high molecular weight polyethylene, or even biodegradable materials
      in orthopedic implant applications. Biomechanical and bioactivity concepts were
      contemplated for the development of PEEK orthopedic implants and a few primary
      clinical studies reported the clinical outcomes of PEEK-based orthopedic
      implants. This study aims to review and discuss the recent concepts and
      contribute further concepts in terms of biomechanical and bioactivity challenges
      for the development of PEEK and PEEK composites in orthopedic implants.

PMID- 25856802
TI  - Volume 35, issue two, provides us with six exciting new articles covering health
      education problems. Introduction.

PMID- 25856803
TI  - Affordable care act: a pyramidal success or failure?

PMID- 25856800
TI  - The role of photodynamic therapy in overcoming cancer drug resistance.
AB  - Many modalities of cancer therapy induce mechanisms of treatment resistance and
      escape pathways during chronic treatments, including photodynamic therapy (PDT).
      It is conceivable that resistance induced by one treatment might be overcome by
      another treatment. Emerging evidence suggests that the unique mechanisms of tumor
      cell and microenvironment damage produced by PDT could be utilized to overcome
      cancer drug resistance, to mitigate the compensatory induction of survival
      pathways and even to re-sensitize resistant cells to standard therapies.
      Approaches that capture the unique features of PDT, therefore, offer promising
      factors for increasing the efficacy of a broad range of therapeutic modalities.
      Here, we highlight key preclinical findings utilizing PDT to overcome classical
      drug resistance or escape pathways and thus enhance the efficacy of many
      pharmaceuticals, possibly explaining the clinical observations of the PDT
      response to otherwise treatment-resistant diseases. With the development of
      nanotechnology, it is possible that light activation may be used not only to
      damage and sensitize tumors but also to enable controlled drug release to inhibit
      escape pathways that may lead to resistance or cell proliferation. 

PMID- 25856804
TI  - Compliance with regimens of existing vaccines in Orumba North local government
      area of Anambra state, Nigeria.
AB  - The factors associated with third dose of diphtheria, pertussis and tetanus
      (DPT3) uptake, a true indicator of compliance with required regimen of vaccines,
      in Anambra state, Nigeria, were investigated in a cross-sectional survey of 600
      mothers (15-49). Being an older mother showed a positive association with
      compliance. Compliance was more among those who used the government health
      facilities for their health needs (chi(2 )= 12.286, p < .001). Satisfactory
      experiences with health service influenced compliance (chi(2 )= 8.542, p = .002).
      Those with good perception (30.1%) complied more (chi(2 )= 42.572, p < .001).
      Those who were aware that immunization protects the children against vaccine
      preventable diseases complied more (chi(2 )= 8.735, p = .002). In conclusion, the
      action-hesitancy model strengthens the Health Belief Model in explaining parents'
      attitude to childhood immunization, as experience and perception of the health
      service influenced uptake more. Health education and campaigns should be directed
      at factors that would encourage mothers to adopt required behaviours. 

PMID- 25856805
TI  - Application of social cognitive theory in predicting childhood obesity prevention
      behaviors in overweight and obese Iranian adolescents.
AB  - The aim of this cross-sectional study was to use social cognitive theory to
      predict overweight and obesity behaviors in adolescent girls in Iran. Valid and
      reliable questionnaires about nutritional and physical activity regarding social
      cognitive theory constructs (self-efficacy, social support, outcome expectations,
      and outcome expectancies), dietary habits, and physical activity were filled by
      172 overweight and obese girl adolescents. The mean age and body mass index were
      13.4 +/- 0.6 years and 28.2 +/- 3.6 kg/m(2), respectively. Body mass index was
      significantly related to hours of television viewing (p = .003) and grams of junk
      food (p = .001). None of the social cognitive theory constructs were found to be
      significant predictors for servings of fruits and vegetables, grams of junk
      foods, minutes of physical activity, and hours of sedentary behaviors. In future,
      more culturally appropriate models need to be developed in Iran that can explain
      and predict prevention behaviors of obesity in Iranian adolescents. 

PMID- 25856806
TI  - Knowledge of nutritional and health needs of children among rural residents of
      Enugu north senatorial zone in Enugu State, Nigeria.
AB  - The article assessed knowledge of the nutritional and health needs of children
      among rural dwellers in Nigeria. Focus group discussions were conducted with all
      male and female groups in four purposively chosen rural communities in Nsukka
      Senatorial zone of Enugu State. These generated data on participants' knowledge
      on the nutritional and health needs of the children as well as their socio
      demographic characteristics. All the participants were married with mean age of
      41 and 36 years for males and females, respectively. The participants had six and
      four children on the average for male and female participants, respectively.
      Findings show that participants demonstrate knowledge of basic dietary needs of
      children; however, actual practice is lacking. Men believe women have the sole
      responsibility for children's nutrition. Exclusive breastfeeding is not adhered
      to by participants. Some reservation still exists about immunization. Sustained
      health education on exclusive breastfeeding and child immunization targeting both
      sexes is still needed. 

PMID- 25856807
TI  - A descriptive study of the progression of the Metabolic Syndrome in middle-aged
      Chinese population.
AB  - This longitudinal study investigated the prevalence of the Metabolic Syndrome
      (MetS) in middle-aged (44-56 years) men and women in China. The presence of the
      components of the MetS was determined in a cohort of 643 persons born in 1956,
      1960-1961, and 1964 in Shanxi Province China in 2008 and 2012. The rate of MetS
      in 2008 was 51.63% (95% CI [44.73, 58.48]) and 37.15% (95% CI [32.56, 41.92]) and
      in 2012 was 50.23% (95% CI [43.35, 57.10]) and 46.26% (95% CI [41.46, 51.11]) for
      men and women, respectively. Increased blood glucose and triglycerides and
      decreased high-density lipoprotein for women, and blood glucose and triglycerides
      for men were the components responsible for the development of MetS from 2008 to
      2012. MetS develops differently between men and women. From age 44 to 56, the
      rate is unchanged among men and increasing among women. 

PMID- 25856808
TI  - Social cognitive maternal-mediated nutritional correlates of childhood obesity.
AB  - The purpose of this investigation was to examine the extent to which the maternal
      facilitated, social cognitive theory constructs of environment, emotional coping,
      expectations, self-control, and self-efficacy predicted child fruit and vegetable
      consumption and sugar-free beverage intake. Instrumentation comprised three
      stages of data collection and analysis. Stage 1 included item generation, face
      and content validity by a panel of six experts, and readability by Flesch Reading
      Ease and Flesch-Kincaid Grade Level tests. Stage 2 assessed stability of the
      theoretical constructs using the test-retest procedure with 30 participants.
      Structural equation modeling was used during Stage 3 to conduct confirmatory
      factor analysis and to establish predictive validity of the models. A total of
      224 respondents participated in this study. Maternal-facilitated home environment
      and self-efficacy were significant predictors of child fruit and vegetable
      consumption while maternal-mediated home environment and emotional coping were
      significant predictors of child sugar-free beverage intake. 

PMID- 25856809
TI  - Do you know what you are drinking?

PMID- 25856810
TI  - Brexpiprazole: another multipurpose antipsychotic drug?
AB  - Brexpiprazole (also known as OPC-34712 or Lu-AF41156) is a novel molecular
      compound chemically and structurally similar to aripiprazole. This drug is
      currently under review by the U.S. Food and Drug Administration as a monotherapy
      for schizophrenia and an adjunct to antidepressant medication for major
      depressive disorder. Additional clinical trials include studies of brexpiprazole
      in attention-deficit/hyperactivity disorder and posttraumatic stress disorder,
      and for agitation associated with dementia of the Alzheimer's type. Brexpiprazole
      is an example that illustrates how pharmacological drug diversity may be
      translated to multipurpose uses.

PMID- 25856811
TI  - Suicide assessment and action for women veterans.
AB  - Many deployed women Veterans, as described in a previous article, have
      experienced similar combat exposure as their male counterparts in wars since
      1990. Upon reintegration, many Veterans visit civilian health facilities with
      behavioral health issues, sometimes voicing and/or attempting suicide. Effective
      nursing assessment and actions are needed to specifically care for this unique
      population. Any suicide variables (e.g., ideation, attempts, completed) are
      concerning; therefore, all women Veterans from the Vietnam, Gulf I, Iraq, and
      Afghanistan wars should be assessed. The first priority is always patient safety.
      Timely and frequent screening for a variety of risk factors, documented for both
      men and women Veterans, and women specifically, are important. Symptomology may
      not become evident for 3 to 15 months into reintegration. Applicable dialogue can
      recognize changing thoughts, judgment, and behavior patterns. Health promotion
      efforts, interventions, and resourceful referrals are provided.

PMID- 25856812
TI  - Assisting clients with disenfranchised grief: the role of a mental health nurse.
AB  - Every society has norms that frame the way individuals grieve. These norms also
      help define significant and insignificant losses. Losses exist within cultures
      that are not discussed or acknowledged because of social stigma. When the ways
      individuals grieve, or the losses they endure, go beyond accepted social norms,
      their grief may be seen as disenfranchised. The current article explores the
      topic of disenfranchised grief and presents methods that could be used by mental
      health nurses to help clients who are experiencing disenfranchised grief.

PMID- 25856814
TI  - Human facial expression recognition using stepwise linear discriminant analysis
      and hidden conditional random fields.
AB  - This paper introduces an accurate and robust facial expression recognition (FER)
      system. For feature extraction, the proposed FER system employs stepwise linear
      discriminant analysis (SWLDA). SWLDA focuses on selecting the localized features
      from the expression frames using the partial F-test values, thereby reducing the
      within class variance and increasing the low between variance among different
      expression classes. For recognition, the hidden conditional random fields (HCRFs)
      model is utilized. HCRF is capable of approximating a complex distribution using
      a mixture of Gaussian density functions. To achieve optimum results, the system
      employs a hierarchical recognition strategy. Under these settings, expressions
      are divided into three categories based on parts of the face that contribute most
      toward an expression. During recognition, at the first level, SWLDA and HCRF are
      employed to recognize the expression category; whereas, at the second level, the
      label for the expression within the recognized category is determined using a
      separate set of SWLDA and HCRF, trained just for that category. In order to
      validate the system, four publicly available data sets were used, and a total of
      four experiments were performed. The weighted average recognition rate for the
      proposed FER approach was 96.37% across the four different data sets, which is a
      significant improvement in contrast to the existing FER methods. 

PMID- 25856815
TI  - Improved repeatability of retinal thickness measurements using line-scan
      ophthalmoscope image-based retinal tracking.
AB  - BACKGROUND AND OBJECTIVE: To assess repeatability and speed of a line-scan
      ophthalmoscope (LSO) image-based tracking system and compare to the point
      scanning approach. PATIENTS AND METHODS: Thirty-five eyes with retinal diseases
      underwent volume scans using two spectral-domain optical coherence tomography
      (OCT) devices: a line-scan tracking Cirrus HD-OCT (Carl Zeiss Meditec; Dublin,
      CA) and point-scan tracking Spectralis HRA+OCT (Heidelberg Engineering,
      Heidelberg, Germany). Eyes were also imaged on the Cirrus HD-OCT with tracking
      disabled. RESULTS: Mean difference in central subfield thickness (CST) between
      consecutive scans was 2.6 um for the Cirrus without tracking, 1.7 um with
      tracking, and 3.6 um for the Spectralis. The repeatability standard deviation was
      3.0 um for the Cirrus without tracking, 1.5 um with tracking, and 4.0 um for the
      Spectralis. Coefficient of variation for the CST was 1.1% for the Cirrus without
      tracking, 0.5% with tracking, and 1.4% for the Spectralis. Mean scan acquisition
      time was 12.3 +/- 6.2 seconds for the Spectralis, 7.8 +/- 6.7 for the Cirrus with
      tracking, and 4.3 +/- 0.6 for the Cirrus without tracking. CONCLUSION: Real-time
      LSO image-based retinal tracking appears to improve repeatability of OCT retinal
      thickness measurements.

PMID- 25856816
TI  - Inner and outer retinal thickness mapping of nonproliferative diabetic
      retinopathy by spectral-domain optical coherence tomography.
AB  - BACKGROUND AND OBJECTIVE: To report inner retinal thickness (IRT), outer retinal
      thickness (ORT), and total retinal thickness (TRT) mapping of nonproliferative
      diabetic retinopathy (DR). PATIENTS AND METHODS: Spectral-domain optical
      coherence tomography (SD-OCT) images were obtained in 31 study participants with
      nonproliferative DR. Semi-automated software generated IRT, ORT, and TRT maps.
      IRT, ORT, and TRT in each macular subfield were compared between groups with and
      without increased central subfield thickness. RESULTS: There were statistically
      significant differences in IRT, ORT, and TRT between groups (P < .007). In
      participants with nonproliferative DR with increased central subfield thickness,
      TRT was significantly increased in parafoveal and perifoveal inferior subfields
      (P < .001). In these subfields, both IRT and ORT were significantly increased (P
      < .007) compared to those in participants without increased central subfield
      thickness. CONCLUSION: Mapping of inner and outer retinal thickness shows promise
      for monitoring depth-specific thickness alterations by macular subfields due to
      DR.

PMID- 25856817
TI  - Spectral-domain optical coherence tomography of the macula in preterm infants
      treated with bevacizumab for retinopathy of prematurity.
AB  - BACKGROUND AND OBJECTIVE: To examine the macula in preterm infants treated with
      bevacizumab (Avastin; Genentech, South San Francisco, CA) for retinopathy of
      prematurity (ROP) using spectral domain optical coherence tomography (SD-OCT).
      PATIENTS AND METHODS: Twenty eyes (of 11 patients) treated with Avastin only or
      in addition to photocoagulation and vitreous surgery were included. Imaging was
      performed with a portable spectral-domain optical coherence tomography (OCT)
      device. Macular measurements, including the foveal and parafoveal index were
      calculated. RetCam (Clarity Medical Systems, Pleasanton, CA) photographs were
      obtained for all patients. RESULTS: Mean age of patients at OCT examination was
      28.9 months (range: 4 to 50 months). Thirteen eyes (65%) developed foveal contour
      (FC), and seven eyes (35%) did not. Earlier gestational age and zone I disease
      were associated with absence of FC development. In patients without FC, two of
      the five eyes had vision better than 20/400, compared with 10 of 11 eyes with FC.
      CONCLUSION: Vision tends to be better in Avastin-treated eyes when an FC is
      present. Morphological characteristics of retinal anatomy may predict visual
      function.

PMID- 25856819
TI  - Gene expression profiling and regression rate of irradiated uveal melanomas.
AB  - BACKGROUND AND OBJECTIVE: Uveal melanoma is the most common primary intraocular
      cancer; however, the molecular features that predict response to therapy are
      poorly understood. Our objective was to determine whether gene expression
      profiling (GEP) is associated with rate of tumor regression after I-125 plaque
      brachytherapy for uveal melanoma. PATIENTS AND METHODS: Retrospective review of
      138 patients with posterior uveal melanoma treated with I-125 plaque
      brachytherapy in which GEP class and 3-month post-radiation ultrasonographic
      tumor thickness data were available. Statistical analysis was performed using t
      test and Fisher's exact test. RESULTS: GEP class assignment was class 1 in 83
      (60.1%) and class 2 in 55 (39.9%) patients. Mean patient age was 60.9 years for
      class 1 and 68.1 years for class 2 tumors (P = .002). Mean initial tumor diameter
      was 13.0 mm for class 1 and 14.1 mm for class 2 tumors (P = .02). Mean initial
      tumor thickness was 5.2 mm for class 1 and 6.1 mm for class 2 tumors (P = .047).
      Three months after I-125 plaque radiotherapy, mean reduction in tumor thickness
      was 26.5% for class 1 and 16.7% for class 2 tumors (P = .03). CONCLUSION: Class 1
      uveal melanoma tumors exhibit more rapid early tumor regression than class 2
      tumors after I-125 plaque radiotherapy.

PMID- 25856818
TI  - Intrasurgical assessment of subretinal tPA injection for submacular hemorrhage in
      the PIONEER study utilizing intraoperative OCT.
AB  - BACKGROUND AND OBJECTIVE: To assess the feasibility of intraoperative OCT (iOCT)
      during pars plana vitrectomy with subretinal tissue plasminogen activator (tPA)
      injection for subretinal hemorrhage. PATIENTS AND METHODS: Eyes that underwent
      vitrectomy and subretinal injection of tPA were identified from the PIONEER
      study, a prospective clinical study assessing the feasibility and utility of iOCT
      in ophthalmic surgery. A microscope-mounted spectral-domain OCT system was
      utilized for iOCT imaging. Standardized scan protocol and image acquisition were
      followed for intraoperative imaging. RESULTS: iOCT was successfully obtained in
      four of four eyes. In all cases, increased subretinal fluid was noted, with
      differential reflectivity visualized between the hemorrhage-tPA interface
      confirming appropriate localization of tPA injection. Image quality variability
      was significant. CONCLUSION: iOCT can successfully be performed during pars plana
      vitrectomy with subretinal tPA injection. Utilizing iOCT, appropriate placement
      of tPA solution and corresponding retinal architectural changes were visualized.

PMID- 25856820
TI  - One-year results from clinical practice of epimacular strontium-90 brachytherapy
      for the treatment of subfoveal choroidal neovascularization secondary to AMD.
AB  - BACKGROUND AND OBJECTIVE: To evaluate clinical feasibility, safety, and efficacy
      of epiretinal strontium-90 brachytherapy in subfoveal choroidal
      neovascularization (CNV) due to age-related macular degeneration (AMD) in eyes
      unresponsive to repeated anti-VEGF injections. PATIENTS AND METHODS: A
      retrospective, single-center study on patients treated with strontium-90
      brachytherapy for CNV secondary to neovascular AMD. Patients underwent pars plana
      vitrectomy with a single 24 Gy dose brachytherapy. They were re-treated with anti
      VEGF injections on an as-needed basis if subretinal or intraretinal fluid was
      detected on optical coherence tomography imaging. RESULTS: Twenty-two patients
      were treated, and 20 completed 12 months of follow-up. Ten patients maintained
      stable vision, eight gained vision, and two lost more than three Snellen lines.
      The mean best corrected visual acuity change from baseline was -8 +/- 5.7
      letters. A mean of 5.5 +/- 4.4 anti-VEGF injections were administered throughout
      12 months. CONCLUSION: Epimacular brachytherapy is feasible in clinical practice.
      While some patients benefit from the treatment and need significantly fewer as
      needed injections, others appear not to react to irradiation treatment after 1
      year of follow-up. Larger numbers of patients are needed to evaluate therapeutic
      efficacy and to determine which patients can benefit from combined radiation and
      anti-VEGF therapy.

PMID- 25856821
TI  - Prevalence of outer retinal tubulation after anti-VEGF therapy for age-related
      macular degeneration.
AB  - BACKGROUND AND OBJECTIVE: To assess whether there is a correlation between anti
      vascular endothelial growth factor (VEGF) therapy and the incidence of outer
      retinal tubulation (ORT) in patients with exudative age-related macular
      degeneration (AMD). PATIENTS AND METHODS: A retrospective review of all patients
      at the Cole Eye Institute who received anti-VEGF injections for exudative AMD and
      underwent optical coherence tomography (OCT) evaluation was performed. A total of
      543 patients were identified and included in the study. The number of treatments
      and the change in Snellen visual acuity from the time of diagnosis until the
      development of ORT were tabulated. RESULTS: Seventy individuals with ORT were
      identified. The data analyzed showed a wide variation in the number of treatments
      until the development of ORT and did not show a significant correlation between
      ORT incidence and decreased visual acuity. CONCLUSION: Although a correlation was
      found between the increased incidence of ORT and length of anti-VEGF treatment,
      there was no evidence of decreased visual acuity, which suggests that the ORT
      might be benign.

PMID- 25856823
TI  - Ambulatory surgery center utilization by vitreoretinal surgeons: 1999-2011.
AB  - BACKGROUND AND OBJECTIVE: To evaluate the utilization rates of ambulatory surgery
      centers (ASCs) in the state of Florida for vitreoretinal, cataract, and glaucoma
      surgical procedures over a 13-year period from 1999 through 2011. PATIENTS AND
      METHODS: Retrospective analysis utilizing the State Ambulatory Surgery Databases
      (SASD) for Florida from 1999 through 2011. ICD-9 codes for vitreoretinal,
      cataract, and glaucoma procedures were queried. Joinpoint regression was used to
      calculate average annual percent change (APC) in ASC utilization by these
      procedures over the 13-year study period and also separately for the years 2007
      to 2011. RESULTS: From 1999 through 2011, APC in ambulatory surgery center
      utilization was +26.4% (P = .0039) for vitreoretinal, +21.3% (P = .012) for
      cataract, and +20.9% (P = .0063) for glaucoma surgery. The APC from 2007 through
      2011 was -1.2% for vitreoretinal (P = .47), -9.2% for cataract (P = .0039), and 
      17.3% for glaucoma surgery (P = .008). CONCLUSION: A significant overall increase
      in ASC utilization by vitreoretinal, cataract, and glaucoma surgeons over the
      study period was seen; however, the most recent 5-year data show that these
      trends may have begun to reverse.

PMID- 25856822
TI  - Central serous chorioretinopathy treated with navigated retinal laser
      photocoagulation: visual acuity and retinal sensitivity.
AB  - BACKGROUND AND OBJECTIVE: To evaluate the effect of navigated retinal laser
      photocoagulation on visual acuity (VA) and retinal sensitivity in eyes with acute
      central serous chorioretinopathy (CSC). PATIENTS AND METHODS: Prospective,
      noncomparative, interventional case series of 30 eyes of 29 patients with acute
      CSC were treated using navigated photocoagulation. Patients were monitored for
      180 days. RESULTS: Mean VA improved from 0.3 +/- 0.1 to 0.1 +/- 0.1 logMAR (P <
      .001). Mean retinal sensitivity within central 8 degrees  and 4 degrees  improved
      from 9.4 +/- 4.7 dB to 14.9 +/- 3.6 dB and from 9.0 +/- 5.6 dB to 14.6 +/- 4.2 dB
      respectively (P < .001). In all cases, a decrease in mean central retinal
      thickness of -50.6 +/- 2.9 um (P < .001) and in mean subretinal fluid thickness
      of -52.0 +/- 3.3 um (P < .001) was observed during follow-up. CONCLUSION:
      Navigated retinal laser photocoagulation demonstrated safety and accuracy for the
      treatment of acute CSC. VA and retinal sensitivity evaluations showed a
      significant improvement associated with resolution of the subretinal fluid during
      follow-up.

PMID- 25856824
TI  - Serum inflammatory markers after rupture retinal laser injury in mice.
AB  - BACKGROUND AND OBJECTIVE: To characterize the cellular, immunological, and
      inflammatory response to retinal photocoagulation of intense rupture laser
      lesions as a model of retinal degenerative diseases. MATERIALS AND METHODS: Seven
      C57BL/6 mice were irradiated using a 532-nm laser to induce 10 retinal burns per
      eye that ruptured Bruch's membrane. Blood was drawn from the saphenous vein
      before and 2 months after laser treatment. The serum was run on antigen
      microarrays with 85 molecular markers associated with retinal degenerative
      diseases. RESULTS: Rupture laser resulted in dramatic changes in the
      immunoglobulin reactivity of most inflammatory markers 2 months after laser
      injury. Approximately two-thirds increased expression and one-third decreased
      expression. Notable markers that were increased included complement C3, CRP,
      PKM2, and aldolase. CONCLUSION: Rupture laser injury causes a change in the serum
      inflammatory markers after 2 months similar to macular degeneration, diabetic
      retinopathy, and cancer-associated retinopathy. This animal model could be used
      as a biomarker for disease stage and activity in retinal degenerations.

PMID- 25856825
TI  - Multimodal imaging in a severe case of hydroxychloroquine toxicity.
AB  - Retinal toxicity from hydroxychloroquine (HCQ) can be detected most readily on
      fundus autofluorescence, spectral-domain optical coherence tomography, and
      multifocal electroretinogram. The authors describe a case of a 60-year-old woman
      with a history of systemic lupus erythematosus undergoing HCQ treatment for 30
      years who presented with visual loss over several years. Examination and
      multimodal imaging showed bilateral retinal pigment epithelium (RPE) changes in a
      bull's-eye distribution associated with cystoid macular edema. A novel imaging
      modality, multi-spectral imaging, appeared sensitive in detecting a bull's-eye
      pattern of RPE disturbance involving the entire macular region of both eyes.
      Cessation of drug was advised with close follow-up.

PMID- 25856826
TI  - Effects of oral propranolol on a juxtapapillary capillary hemangioma: a single
      subject pilot study.
AB  - Oral propranolol hydrochloride has been proven effective in treating infantile
      hemangiomas, and its potential efficacy in choroidal hemangiomas has been
      suggested. A 57-year-old woman with a juxtapapillary capillary hemangioma was
      treated with oral propranolol at Nagoya Medical Center in Japan in 2012. Although
      the condition of this patient partially improved, oral propranolol did not appear
      to have a critical therapeutic effect. To the authors' knowledge, this is the
      first pilot study to describe a case in which oral propranolol was used as a
      therapeutic approach for a retinal hemangioma.

PMID- 25856827
TI  - Resolution of exudative changes refractory to ranibizumab after aflibercept
      injections at the margin of inferior staphyloma in tilted disc syndrome.
AB  - An 81-year-old woman presented with blurred vision in the left eye. Best
      corrected visual acuity was 20/100. Ophthalmologic examination in the left eye
      revealed tilted disc syndrome with exudative change at the margin of inferior
      staphyloma. The exudative change persisted despite monthly intravitreal
      ranibizumab injections for 5 months. Subsequently, two intravitreal aflibercept
      injections 1 month apart were substituted for the ranibizumab injections,
      resulting in successful resolution of the exudative change.

PMID- 25856828
TI  - Long-term follow-up of astrocytic hamartoma of the optic disc associated with
      gyrate atrophy.
AB  - This is a case report of a 15-year-old boy with multiple small peripapillary
      white growths in the right eye in the setting of gyrate atrophy. Over 3 years of
      follow-up, these lesions became more clearly delineated as astrocytic hamartomas
      of the retina and optic disc. In the setting of gyrate atrophy, astrocytic
      hamartomas are extremely rare. This report represents the second published case
      and includes characterization of these tumors using spectral-domain optical
      coherence tomography.

PMID- 25856829
TI  - Atypical presentation of acute-onset endophthalmitis after uncomplicated pars
      plana vitrectomy.
AB  - A 70-year-old woman presented with signs of acute-onset endophthalmitis within 24
      hours of surgery, with retinal hemorrhages and vascular changes in the absence of
      pain or significant inflammation. She had undergone uncomplicated 25-gauge pars
      plana vitrectomy for epiretinal membrane with presenting visual acuity of 20/40-
      and significant distortion. Vitreous culture revealed Staphylococcus epidermidis.
      Final visual acuity was no light perception with persistent pain, and the patient
      ultimately underwent enucleation. Although rarely, acute-onset postoperative
      endophthalmitis can present as retinal vasculitis with intraretinal hemorrhages
      and mild inflammation.

PMID- 25856830
TI  - Perivascular hypofluorescence in frosted branch angiitis.

PMID- 25856831
TI  - The interaction of new piroxicam analogues with lipid bilayers--a calorimetric
      and fluorescence spectroscopic study.
AB  - The purpose of the present paper was to assess the ability of new piroxicam
      analogues to interact with the lipid bilayers. The results of calorimetric and
      fluorescence spectroscopic experiments of two new synthesized analogues of
      piroxicam, named PR17 and PR18 on the phase behavior of phospholipid bilayers and
      fluorescence quenching of fluorescent probes (Laurdan and Prodan), which
      molecular location within membranes is known with certainty, are shown in present
      work. The presented results revealed that, depending on the details of chemical
      structure, the studied compounds penetrated the lipid bilayers.

PMID- 25856832
TI  - A comparison of tests for Hardy-Weinberg equilibrium.
AB  - The various tests for the goodness of fit of a population to Hardy-Weinberg
      equilibrium are compared with respect to their power and the accuracy of their
      distributional approximations. The tests are similar in terms of power. However,
      when one or more alleles are rare (with frequencies of less than .45 to .21 for n
      = 10 and 200, respectively) some of the tests are not able to detect outbreeding.
      When all but one allele are rare (frequencies of less than .40 to .15 for n = 10
      and 200, respectively) none of the tests are able to detect outbreeding. In terms
      of distributional assumptions, there are two situations: (i) Test of hypothesis
      (when a preset significance level is chosen and the null hypothesis accepted or
      rejected at that level); here the chi square test with conditional expectations,
      the Freeman-Tukey test and the Mantel-Li test, all without continuity correction,
      were found to be best; they were closely followed by the chi square test and
      conditional chi square test, both with a continuity correction of 1/4, and by the
      Elston-Forthofer average test. (ii) Test of significance (when the obtained level
      of significance is used as strength against the null hypothesis); here the chi
      square test and conditional chi square test, both with a continuity correction of
      1/4, and the average test were found to be best.

PMID- 25856833
TI  - Allosteric modulation of Callinectes sapidus hemocyanin by binding of L-lactate.
AB  - Hemocyanin of the blue crab Callinectes sapidus has the typical structure of
      crustacean hemocyanins in that its smallest in vivo structure is a hexamer of
      subunits each having a molecular mass of approximately 75 000. As found in the
      blood, Callinectes hemocyanin consists of a mixture of hexamers and dodecamers
      (typically 1:4). As in other crustacean hemocyanins, the affinity with which
      oxygen binds to the binuclear copper site has been reported to be very sensitive
      to pH and to a variety of inorganic allosteric effectors. We report here the
      interaction of L-lactate, a natural metabolite,with the native hemocyanin and
      with chromatographically purified hexamers and dodecamers. Under ionic conditions
      that approximate those found physiologically, the addition of 10 mM L-lactate to
      native Callinectes hemocyanin substantially increases its oxygen affinity (Delta
      log P(50) = -0.28). The data from lactate titrations were fit to a theoretical
      equation,and the best fit was obtained with a lactate dissociation constant of
      1.8 mM for the oxy state and 2.2 lactate binding sites for every 6 oxygen binding
      sites. Independent measurements by ultrafiltration techniques indicated a
      dissociation constant of 3.2 mM with 2.8 lactate binding sites per 6 oxygen
      binding sites. The two sets of data clearly indicate that there is less than one
      lactate binding site per oxygen binding site. The fit to the titration was not
      improved with the assumption of more than one class of lactate binding site. The
      hexamers and dodecamers of native Callinectes hemocyanin are not in equilibrium
      and are stable after separation by gel-filtration chromatography. Polyacrylamide
      gel electrophoresis of the subunits of the dissociated dodecamers shows five
      major bands.Two of these bands, which constitute one-sixth of the total
      dodecameric hemocyanin, do not appear upon gel electrophoresis of dissociated
      hexamers. The oxygen affinities of the hexameric and dodecameric hemocyanin forms
      are similar to one another but show differences in their sensitivity to L
      lactate.The oxygen affinity of native Callinectes hemocyanin was increased
      appreciably more by L-lactate than by glycolate,D-lactate, and pyruvate (listed
      in decreasing order of effectiveness).Propionate, acetate, succinate, D-alanine,
      and L-alanine were without effect, thus illustrating the selectivity of the L
      lactate effect on the hemocyanin. We found the magnitude of the Bohr effect to be
      unchanged by the addition of L-lactate over the pH range 7.5-8.0. Moreover, there
      is no significant effect of L-lactate on the aggregation state of the hemocyanin
      or on its 340-nm copper-oxygen absorption band.The foregoing results are
      consistent with the role of L-lactate as a specific allosteric effector of
      Callinectes hemocyanin that acts by preferential binding to a stereospecific site
      of the oxy hemocyanin.

PMID- 25856835
TI  - AORN position statement on advanced practice registered nurses in the
      perioperative environment.

PMID- 25856834
TI  - Comparison of the physical and functional properties of the 48-subunit native
      molecule and the 24- and 12-subunit dissociation intermediates of Limulus
      polyphemus hemocyanin.
AB  - Limulus hemocyanin is a 48-subunit complex that is composed of eight
      immunochemically distinct subunits.Conditions were established that allowed for
      comparison of the structural and functional properties of the native molecule
      with those of its 24-subunit and 12-subunit dissociation products by analytical
      ultracentrifugation, functional analysis,stopped-flow light scattering, and
      circular dichroism spectroscopy.The 48-subunit complex was found to be
      specifically stabilized by calcium ions. When 48-subunit molecules at pH7 were
      rapidly mixed with a pH 9 buffer containing a calcium chelator, the dissociation
      to monomers was complete within minutes. The rate is dependent upon the
      concentration and Ca2+ affinity of the chelator, consistent with the formation of
      a transient chelator-calcium ion-protein complex during the dissociation process.
      Dissociation to the level of 24-subunit molecules occurs much more slowly than
      does the dissociation of 24-subunit molecules to monomers. The dissociation to
      monomers, from 48-, 24-, or 12-subunit aggregates, is a highly cooperative
      process, and the corresponding reassembly reactions show appreciable hysteresis.
      In contrast, the reversible dimerization of dodecamers appears to be a rapidly
      equilibrating system. The varied aggregation states of Limulus hemocyanin are
      characterized by different circular dichroism spectra. These are, however, not
      unambiguously associated with the aggregation-state changes in that the CD
      spectra were found to be sensitive to pH under conditions where the aggregation
      state was unaltered. The 24-subunit complex of Limulus hemocyanin was found to be
      similar in its functional properties to the native 48-subunit aggregate. No
      unique functional properties thus appear to be associated with the 48-subunit
      ensemble that is found only in horseshoe crabs.Upon dissociation to the level of
      dodecamers, the reverse Bohr effect, cooperatively, and modulation of oxygen
      affinity by NaCl are still present although diminished in magnitude.Taken
      together, these studies clearly indicate that the interactions that stabilize
      dodecamers are different in pH and ion sensitivity from the interactions that are
      involved in formation of the 24-subunit complex from dodecamers and that these in
      turn differ from the interactions that stabilize the 48-subunit complex. These
      results are consistent with other lines of evidence that indicate that
      interactions at these different levels are dominated by structurally and
      functionally distinct types of subunits.

PMID- 25856836
TI  - Evidence appraisal of Chiang HY, Herwaldt LA,  Blevins AE, Cho E, Schweizer ML.
      Effectiveness  of local vancomycin powder to decrease surgical  site infections:
      a meta-analysis.  Spine J. 2014;14(3):347-407.

PMID- 25856837
TI  - Recent outbreak stimulates national  dialogue on endoscope contamination 
      concerns.

PMID- 25856838
TI  - Addressing the complexities of flexible  endoscope reprocessing.

PMID- 25856839
TI  - Care of the patient receiving local  anesthesia.

PMID- 25856840
TI  - Transformational leaders in the  perioperative setting.

PMID- 25856841
TI  - Dealing with a crisis.

PMID- 25856842
TI  - Ensuring a sustainable future   for veterinarians.

PMID- 25856843
TI  - Australia Day honours 2015.

PMID- 25856844
TI  - Veterinary workforce models--what they've been doing in America.

PMID- 25856845
TI  - Restraints of trade in common law contracts.

PMID- 25856846
TI  - Room to improve in government commitment   to animal protection.

PMID- 25856848
TI  - How to deal with difficult clients.

PMID- 25856847
TI  - Sustainable animal management in Kakadu.

PMID- 25856849
TI  - Neither gloom nor glee from   systematic review of veterinary homeopathy.

PMID- 25856850
TI  - No greater challenge.

PMID- 25856851
TI  - No quick fix for Texas' shortage of psychiatrists.

PMID- 25856852
TI  - Texas' child mental health system a "mess".

PMID- 25856853
TI  - Reducing mental illness stigma challenging.

PMID- 25856854
TI  - Untreated mental illness in children devastating, costly.

PMID- 25856855
TI  - Poor prognosis for mental health care in Texas' EDs.

PMID- 25856856
TI  - [The advantages of a large tertiary academic medical center in managing disease
      and promoting health: a glimpse into Sheba Medical Center].
AB  - Academic medical centers have traditionally been at the forefront of medical
      training for the next generation of clinicians, providing the highest quality of
      care and conducting translational and clinical research. The Sheba Medical Center
      is the largest academic medical center in Israel and, as such, has been shaping
      the medical scene in Israel since the birth of the State. The cornerstones of the
      Sheba Medical Center have always brought together the best clinicians, fostering
      a multidisciplinary approach environment, encouraging research and innovation
      from lab to bedside and compassionate, patient-centered care. Clinicians at Sheba
      enjoy the wide variety of clinical conditions that are present at the hospital,
      the existence of multiple professions and specialties from neonates to geriatric
      rehabilitation and the advanced technologies available to patients. In this
      special issue we describe some of the important work that takes place at Sheba,
      while emphasizing the above-mentioned advantages.

PMID- 25856857
TI  - [A rare neurologic syndrome due to a common medical condition].
AB  - We describe a patient with hypertension, diabetes mellitus, recurrent strokes,
      congestive heart failure, chronic atrial fibrillation and renal failure,who was
      hospitalized twice for chorea. A thorough work-up excluded all common causes for
      chorea in the elderly. The patient's HbA1c was > 17% and the brain computerized
      tomography revealed dense lesions in the basal ganglia compatible with Chorea
      Hyperglycemia Basal Ganglia syndrome. This syndrome includes a combination of
      chorea, hyperglycemia and dense lesions in the basal ganglia. The hemichorea in
      this syndrome is provoked by non-ketotic hyperglycemia and improves with insulin
      treatment. The radiographic picture also improves after there is control of
      glucose levels and clinical improvement.

PMID- 25856858
TI  - [A novel system for minimally invasive transplantation of bone marrow derived
      stem cells as a thin layer in the subretina and extravascular spaces of the
      choroid--for treatment of retinal degeneration].
AB  - BACKGROUND: Incurable retinal degenerations affect millions worldwide. Stem cell
      transplantation rescued visual functions in animal models of retinal
      degeneration. In those studies, cells were transplanted in subretinal "blebs". A
      limited number of cells could be injected and photoreceptor rescue was restricted
      to areas in proximity to the injection sites. PURPOSE: To develop a minimally
      invasive surgical system for stem cell transplantation in the subretina and
      extravascular spaces of the choroid. METHODS: A novel syringe with flexible
      needle and adjustable pin was developed. Human bone marrow mesenchymal stem cells
      [hBM-MSCs) were transplanted in the eyes of RCS rats and NZW rabbits through a
      longitudinal triangular scleral incision. No immunosuppressants were used.
      Retinal function was determined by electroretinogram analysis and retinal
      structure was determined by histological analysis and optical coherence
      tomography (OCT). RESULTS: Transplanted cells were identified as a thin layer
      across the subretina and extravascular spaces of the choroid. In RCS rats, cell
      transplantation delayed photoreceptor degeneration across the entire retina and
      significantly enhanced retinal functions. No changes in retinal functions were
      recorded in rabbits following transplantation. No retinal detachment or choroidal
      hemorrhages were observed. CONCLUSIONS: The novel syringe facilitates cell
      transplantation across the subretina and extravascular spaces of the choroid
      using a minimally-invasive procedure. Human BM-MSC transplantation using this
      system ameliorates retinal degeneration in the animal model. DISCUSSION: This new
      transplantation system may increase the therapeutic effect of other cell-based
      therapies and therapeutic agents. This study is expected to lead directly to
      phase I clinical trials for autologous hBM-MSCs transplantation in patients with
      retinal degeneration.

PMID- 25856859
TI  - [Low ALT activity amongst patients hospitalized in internal medicine wards is a
      widespread phenomenon associated with low vitamin B6 levels in their blood].
AB  - BACKGROUND: Monitoring the activity of ALT (SGPT) in the blood is part of the
      routine, clinical-laboratory follow-up in hospitalized patients. In most cases,
      activity levels which are above the normal range are considered pathology, mostly
      related to lysis of hepatocytes, as in cases of hepatitis. Little has been
      investigated and published in regard to cases in which the ALT activity level is
      lower than normal. PATIENTS AND METHODS: Since normal ALT activity is regarded
      essential for normal metabolism and homeostasis, we decided to evaluate the
      extent to which low ALT levels are found in healthy and hospitalized patient
      populations and to characterize its circumstances and etiology. Furthermore, we
      measured the blood concentration of vitamin B6 (being the source for the ALT co
      factor, Pyridoxal-5-Phosphate) in a random sample of patients with lower than
      normal ALT activity level. RESULTS AND CONCLUSIONS: The results of the current
      study showed a high prevalence, exceeding a third of hospitalized patients in
      internal medicine departments have low levels of ALT in the serum, and that a
      linear correlation (p = 0.0004, r = 0.47) exists between lower than normal ALT
      activity and low concentrations of vitamin B6 in the serum. The authors attribute
      these findings to a high prevalence of frailty amongst hospitalized patients. We
      aim to conduct further investigations intended to better characterize
      quantifiable parameters of frailty amongst our patient population.

PMID- 25856860
TI  - [Exertional heat stroke].
AB  - Exertional heat stroke (EHS) is a clinical syndrome of hyperthermia,
      encephalopathy and multi-organ dysfunction that can be irreversible and fatal.
      Prompt recognition and immediate, aggressive total body cooling can prevent
      progression of the clinical syndrome, but even a short delay can exacerbate the
      effects of hyperthermic-induced changes. EHS is linked to an inflammatory
      response that is akin to the systemic inflammatory response syndrome (SIRS).
      However, because EHS is not a common problem in most hospital intensive care
      units and is not in the usual list of SIRS causes, it may easily be overlooked.
      The present case report will highlight the preliminary clinical manifestations of
      the syndrome, the initial optimal treatment, and its clinical sequelae.

PMID- 25856861
TI  - [Clinical characteristics of dysthyroid optic neuropathy].
AB  - PURPOSE: To describe the clinical presentation, management and outcome of
      dysthyroid optic neuropathy (DON) patients in order to find markers for this
      diagnosis among Graves orbitopathy (GO) patients. METHODS: We conducted a
      retrospective review of the medical records of 15 patients presenting with
      clinical and radiologic evidence of DON, from a series of 131 patients with
      Graves orbitopathy, treated at our health care center between the years 1999 and
      2008. The worse eye of each of the 15 DON patients was determined according to
      visual acuity and visual field defects, and was paired with an eye of a matched
      patient from the GO group. Paired comparisons were performed in order to
      appreciate the differences in the rates of various signs and symptoms between
      both groups. RESULTS: A total of 15 patients (11%), mean age 55 years (range 37
      76 years) were diagnosed with DON, (53%) of them were smokers. The most common
      manifestations among DON patients were proptosis (78%), visual field defects
      (76%) and restriction of abduction (73%). In a paired comparison between the
      worse eye of DON patients and their counterparts in the GO group, statistically
      significant differences were noted in the rate of proptosis (p = 0.02), extent of
      visual field damage (p = 0.001), visual field mean deviation (p = 0.02) and
      abduction limitation (p = 0.02). A trend with no statistical significance was
      demonstrated for the difference in adduction limitation (p = 0.06). CONCLUSIONS:
      The clinical presentation and management of dysthyroid optic neuropathy patients
      is described in a cohort of 15 patients. As visual field defects and restriction
      of abduction were the most common signs with the diagnosis of optic neuropathy,
      we recommend follow-up to include routine visual field screening in Graves'
      orbitopathy patients. Treatment with intravenous corticosteroids and
      decompressive surgery was shown to be effective in our cohort.

PMID- 25856862
TI  - [A snapshot: the causes of admission and complications to an acute coronary care
      unit in a tertiary center in Israel].
AB  - BACKGROUND: The reasons for admission to the Acute Coronary Care Unit (ACCU) have
      changed in the past few years. The classical cause of acute coronary syndrome
      sets aside the causes of acute heart failure and post-procedural complications.
      There is also a change in the demographic characteristics and co-morbidities of
      the admitted patients. OBJECTIVES: The aim of this study is to illustrate the
      current causes of admission and complications during hospitalization in a
      tertiary center. METHOD: We compiled a computerized prospective registry during
      the months of January to March 2014. The registry includes the cause of
      admission, demographic characteristics, co-morbidities, interventions and
      clinical outcomes. RESULTS: A total of 257 patients were admitted to the ACCU
      with a calculated sum of 937 hospitalization days. The average age was 67 +/- 15;
      a third of the patients were above the age of 75 and a third were female; 100
      patients have presented with other co-morbidities such as COPD, chronic renal
      failure, CVA or malignancy; and 46% of the patients were admitted due to acute
      coronary syndrome (ACS). Other causes were acute heart failure, shock and post
      procedural complications. The average length of hospitalization was 2.9 +/- 1.7
      days for ACS patients compared to 4.3 +/- 5 days due to other causes.
      Approximately 25% had developed acute heart failure during their hospital stay;
      most of them were older with higher rates of co-morbidities. The duration of
      hospitalization was longer in those patients, 5.5 +/- 5 days, compared to 3.2 +/-
      4 (p < 0.005); 20% of the patients needed mechanical ventilation; 8.3% had acute
      renal failure; 4.7% acquired infection while hospitalized; 3.1% had major
      bleeding and 1.9% had arrhythmias. The total mortality rate was 2.3%. Patients
      who presented with ACS had a mortality rate of 1% compared to patients who were
      admitted due to heart failure or shock who had a mortality rate of 10.4% in this
      period. CONCLUSION: We have presented the current trend of admission to the ACCU
      with a shift from ACS to other cardiac causes such as acute heart failure, shock
      or peri-procedural complications. The rate of co-morbidities and hospital
      complications is increasing as the patients' age increases. This shift of
      patients' characteristics requires a re-examination of the role of the medical
      staff in this new era. There is a need to increase funding for acquiring new
      technology, staff education and reinforcing current staff.

PMID- 25856863
TI  - ["The Talpiot medical leadership program"--advancing the brightest young
      physicians and researchers to fill future leadership roles].
AB  - BACKGROUND: The modern medical world is dynamic and boundless. There is a need
      for the medical training system currently existing in Israel to undergo a
      thorough conceptual change in order to strive for excellence and innovation on
      the one hand and to prevent the "brain drain" from Israel on the other.
      OBJECTIVE: To report on the "Talpiot" program at the "Sheba Medical Center",
      which identifies, promotes and prepares the most talented young doctors to fill
      key positions in the fields of medicine and health in Israel. METHODS: This study
      is based on a project with the same name in the Israeli Defense Forces (IDF). It
      promotes an elite group of physicians and researchers at the medical center and
      includes the provision of scholarships, personal guidance and customized
      educational opportunities for its members. Conversely, every member in the
      program is committed to complete five years of training followed by another five
      years as a senior physician or a researcher at the medical center. RESULTS: Since
      2002, there have been six cycles of "Talpionaires". The current 46 members of the
      program fill key leadership roles in the medical center and are considered
      leaders in their field. Among the program's alumni are managers of institutes,
      units and research institutes. This group is responsible for the publication of
      hundreds of scientific papers studies and dozens of patents in medical
      technology. Some of them have progressed academically far beyond their peers.
      CONCLUSIONS: Excellence programs are an integral part of any institution which
      considers itself a leader, both in medicine and beyond. The exciting and
      visionary "Talpiot" program is Sheba's contribution to the quality of the medical
      system in the country of Israel in the long run. Promoting young doctors and
      researchers to become leaders in the Israeli medical system is an integral part
      of national interests.

PMID- 25856864
TI  - [Dacryocystorhinostomy (DCR) under local anesthesia].
AB  - INTRODUCTION: Dacryocystorhinostomy (DCR) is performed using an external or
      endoscopic endonasal approach under general anesthesia (GA) or under sedation. In
      our department these operations are performed mainly under local anesthesia (LA)
      without sedation. PURPOSE: To examine the intraoperative and postoperative
      success rates of primary DCR under LA and GA using the external or endonasal
      approach. METHODS: The study group of this retrospective research included all
      patients who underwent a primary DCR in our department in 2009-2012 due to an
      acquired nasolacrimal duct obstruction. The main outcome measure was
      postoperative success defined as complete or significant improvement in tearing
      and a patent ostium. Intraoperative success rate was defined as the ability to
      complete the operation under LA. RESULTS: The study group included 139 patients.
      The success rate was 87.1% (121 patients). Success rates were similar for the
      external and endoscopic approaches (88.6% vs. 82.4%, respectively, p = 0.348).
      The success rate for surgeries performed under GA was higher than LA (96.7% vs.
      84.9%, respectively, p = 0.019). The mean age of patients who were operated under
      GA was significantly younger than those under LA (43.6 vs. 65.7 years,
      respectively, p < 0.005). Conversion GA was only needed in 1 patient (0.7%).
      CONCLUSION: Most DCR surgeries can be performed under LA without sedation.
      Success rates found in our study are comparable with previous publications,
      similar for external or endoscopic approaches, and better under GA than LA. This
      difference may be related to the age difference between the two groups.

PMID- 25856865
TI  - [Do poor-responder patients benefit from increasing the daily gonadotropin dose
      from 300 to 450 IU during controlled ovarian hyperstimulation for IVF?].
AB  - OBJECTIVE: We aim to evaluate the IVF-ET outcome in patients receiving a high
      daily dose (300 IU) of gonadotropins during controlled ovarian hyperstimulation
      (COH) for IVF and to assess the role of increasing the daily dose to 450 IU on
      improving outcome. PATIENTS AND METHODS: All consecutive women admitted to our
      IVF unit during an 11 year period who underwent COH consisting of daily
      gonadotropin dose of 300 IU were included in the study. The ovarian stimulation
      characteristics, number of oocytes retrieved, number of embryo transferred and
      pregnancy rate were assessed. We also evaluated the subsequent cycle, using daily
      gonadotropin doses of 450 IU, among those patients who did not conceive using the
      300 IU daily gonadotropin dose. RESULTS: Nine hundred and forty-nine consecutive
      IVF cycles were evaluated. Patients who conceived using the daily gonadotropin
      dose of 300 IU (n = 133, 14% pregnancy rate) had significantly longer
      stimulation, yielded higher numbers of oocytes retrieved, fertilization rate and
      number of embryos transferred, compared to those who did not conceive. Moreover,
      while comparing IVF cycles using daily gonadotropin doses of 300 IU to 450 IU (n
      = 117), no in-between group differences were observed, except for significantly
      higher yields of oocytes retrieved. Moreover, cycles using daily gonadotropin
      doses of 450 IU resulted in a 7.7 live-birth rate. CONCLUSIONS: In poor
      responders undergoing COH with a daily gonadotropin dose of 300 IU, increasing
      the dose to 450 IU resulted in significantly higher oocyte yields and a
      reasonable live birth rate.

PMID- 25856866
TI  - [Corneal collagen cross-linking novel technique for prevention of keratoconus
      progression: results after one-year at the Sheba Medical Center].
AB  - BACKGROUND: Keratoconus is a progressive corneal degenerative disease that
      appears in young adults and causes progressive myopia and irregular astigmatism
      affecting visual acuity. The quality of life may be severely impaired in these
      young adults. Corneal Collagen Cross-Linking (CXL) is a novel technique aimed at
      stopping disease progression. OBJECTIVE: To evaluate the refractive and
      topographic outcome 12 months after CXL treatment in patients with progressive
      keratoconus. METHODS: In this retrospective case series, 15 eyes of 14 patients
      with progressive keratoconus were treated with standard CXL. Patients were
      assessed preoperatively, at week 1 and at months 1, 3, 6, and 12 after treatment.
      Outcome measures included best-corrected visual acuity (BCVA) refraction,
      biomicroscopy and fundus examination, corneal topography and pachymetry. RESULTS:
      Comparing the preoperative data with 12 months postoperative results, we observed
      stabilization of the average keratometry values 51.2 to 50.67 (diopters), P =
      0.605. The BCVA values remained stable 0.47 to 0.57 (decimal point) P = 0.6626.
      CONCLUSION: Our series of patients with progressive keratoconus supports the
      effect of crosslinking to prevent disease progression. Regularization of the
      corneal keratometry values and minor improvement of the visual acuity may be
      additional benefits of this procedure.

PMID- 25856867
TI  - [Syphilis snarls].
AB  - Syphilis is an infectious disease. It is unique and interesting, and even to this
      day it continues to be a major challenge to the medical community in the
      prevention of the spread, the diagnosis and treatment of the disease. In recent
      years in Israel, 200 new cases have been revealed annually. During this period,
      several reports were published on the outbreaks of the disease. We believe that
      due to the increase in the rate of patients with the disease there is a strong
      need to educate the medical staff about the disease and to raise awareness
      regarding the symptoms of the disease, methods of diagnosis, increased risk
      populations, and methods of treatment. In this article we present four cases of
      syphilis that we encountered in our institution, which presented relatively in
      different ways. Furthermore, in these cases the diagnosis was not simple. So it
      is important to be aware that this disease still exists and must be recognized in
      order to know how to diagnose it.

PMID- 25856868
TI  - [Excellence and creativity: the story of Sheba Medical Center].

PMID- 25856869
TI  - [The sick building syndrome as a part of 'ASIA' (autoimmune/auto-inflammatory
      syndrome induced by adjuvants)].
AB  - The entity 'sick building syndrome' is poorly defined and comprises of a set of
      symptoms resulting from environmental exposure to a work or a living environment.
      The symptoms are mainly "allergic"-like and include nasal, eye, and mucous
      membrane irritation, dry skin as well as respiratory symptoms and general
      symptoms such as fatigue, lethargy, headaches and fever. The Autoimmune [Auto
      inflammatory] Syndrome Induced by Adjuvants (ASIA) is a wider term which
      describes the role of various environmental factors in the pathogenesis of immune
      mediated diseases. Factors entailing an immune adjuvant activity such as
      infectious agents, silicone, aluminium salts and others were found in association
      with defined and non-defined immune mediated diseases. The sick building syndrome
      and ASIA share a similar complex of signs and symptoms and probably the same
      immunological mechanisms which further support a common denominator.

PMID- 25856870
TI  - Metabolic correction: a functional biochemical mechanism against disease--Part 1:
      concept and historical background.
AB  - Human physiology depends on countless biochemical reactions, numerous of which
      are co-dependent and interrelated. The speed and level of completion of reactions
      usually depend on the availability of precursors and enzymes. The enzymatic
      activity depends on the bioavailability of micronutrient cofactors such as
      vitamins and minerals. In order to achieve a healthy physiological state, the
      organism requires that biochemical reactions occur at a controlled rate. To
      achieve this state it is required that metabolic reactions reach what can be
      considered an optimal metabolic equilibrium. A combination of genetic makeup,
      dietary patterns, trauma, disease, toxins, medications, and environmental
      stressors can elevate the demand for the nutrients needed to reach this optimal
      metabolic equilibrium. In this, part 1, the general concept of metabolic
      correction is presented with an elaboration explaining how this concept is
      increasing in importance as we become aware of the presence of genetic variants
      that affect enzymatic reactions causing metabolic disturbances that themselves
      favor or promote the disease state. In addition, part 1 reviews how prominent
      scientists have contributed in fundamental ways to our understanding of the
      importance of micronutrients in health and disease and in the development of the
      metabolic correction concept.

PMID- 25856871
TI  - Metabolic correction: a functional biochemical mechanism against disease--Part 2:
      mechanisms and benefits.
AB  - A healthy physiology depends on a plethora of complex interdependent biochemical
      reactions. In order for these reactions to occur suitably, the enzymes and
      cofactors that regulate their flow must be present in the proper balance. The
      term metabolic correction is used to describe a biochemical-physiological process
      that improves cellular biochemistry as a means to an individual's achieving
      metabolic or physiological optimization. Part 2 discusses how metabolic
      correction, through the increase of cofactors, can supply unmet enzyme needs and
      compensate for nutritional deficiencies induced by improper nutritional intake or
      by the increased demand for nutrients caused by genetics, health conditions,
      medications, or physical or environmental stressors. Nutrient insufficiencies are
      causing an increase in morbidity and mortality, at great cost to our society. In
      summary, metabolic correction improves enzymatic function and satisfies the
      increasing demand for nutrients. Metabolic correction can have a significant
      impact on the reduction of morbidity and mortality and their financial cost to
      our society and contribute to improving health and well-being.

PMID- 25856872
TI  - Usefulness of the culturally adapted oxygen-cost diagram in the assessment of
      dyspnea in Puerto Rico.
AB  - OBJECTIVE: Breathlessness is a common and disabling symptom of pulmonary disease.
      Measuring its severity is recommended as such measurements can be helpful in both
      clinical and research settings. The oxygen-cost diagram (OCD) and the Medical
      Research Council (MRC) dyspnea scale were developed in English to measure
      severity of dyspnea. These scales were previously translated to Spanish and
      adapted for use in a Hispanic population. The objective of this study is to
      assess the psychometric properties of these scales. We propose the scales
      correlate well with measures of physiological impairment. METHODS: Subjects
      having pulmonary disease rated their perceptions of dyspnea using the scales,
      performed a spirometry test, and did a 6-min walk. Spearman correlation
      coefficients (p) were used to correlate dyspnea scores with spirometric
      parameters and distance walked (6MWD). RESULTS: Sixty-six patients having stable
      asthma (n = 36), chronic obstructive pulmonary disease (n = 19), or interstitial
      lung disease (n = 11) participated in the study. OCD scores showed a significant
      correlation with FEV1 (p = 0.41; p < 0.01), FEV1% (p = 0.36; p < 0.01), FVC (p =
      0.44; p < 0.01), and FVC% (p = 0.37; p < 0.01) in the study population. The OCD
      scores were highly correlated with 6MWD (p = 0.59, p < 0.01). The MRC dyspnea
      scale showed significant inverse correlation with FEV1 (p = -0.34; p < 0.01) and
      6MWD (p = -0.33; p < 0.05), but the correlations were weaker compared to the
      correlations with the OCD scale. CONCLUSION: The severity of breathlessness as
      measured by the adapted Spanish OCD showed a moderate to high correlation with
      spirometric parameters and 6MWD; therefore, the adapted OCD should prove to be
      useful in Puerto Rico.

PMID- 25856873
TI  - Binge drinking as a risk factor for violence among secondary school students in a
      nationally representative sample in Puerto Rico.
AB  - OBJECTIVE: The objective of this study was to determine the association between
      binge drinking and violence in a representative sample of secondary-school
      students in Puerto Rico. METHODS: Consulta Juvenil VII (a biennial survey of
      school-aged youths in Puerto Rico) has a representative sample of adolescent
      students in Puerto Rico. A multi-stage stratified cluster sampling design was
      used. The sampling frame of Consulta Juvenil VII includes all the public and
      private schools registered with the Department of Education and the Council of
      General Education in Puerto Rico. The study utilizes a self-administered
      questionnaire that was translated and adapted from the "Student Survey of Risk
      and Protective Factors and Prevalence of Alcohol, Tobacco, and Other Drug Use".
      "Binge drinking" was defined as having 5 or more alcoholic drinks in a row during
      the 30 days preceding the survey. RESULTS: Almost 20% of the sample members
      reported that at least 1 instance of binge drinking had taken place during the 2
      weeks prior to the survey (17.7%). After controlling for gender, age, school
      level, the type of system, and the parents' educational levels, the odds of a
      given binge drinker reporting violent behaviors were 5 times greater than the
      odds among non-binge drinkers (OR: 5.6; 95% CI: 4.7-6.7). CONCLUSION: The study
      shows an association between binge drinking and violence in Puerto Rican
      adolescents, indicating that Hispanic youths who abuse alcohol may be at
      increased risk of violence. These findings suggest that violence prevention
      programs should be integrated with substance use prevention programs. [PR Health

PMID- 25856874
TI  - Biological screening of select Puerto Rican plants for cytotoxic and antitumor
      activities.
AB  - OBJECTIVE: The objective of this study was to evaluate the cytotoxic and
      anticancer activities of extracts from 7-species of endemic and native plants
      from Puerto Rico. METHODS: The plant species selected for this study were Canella
      winterana, Croton discolor, Goetzea elegans, Guaiacum officinale, Pimenta
      racemosa, Simarouba tulae, and Thouinia striata. The dried plant material was
      extracted with a 1:1 mixture of CH2CI2-MeOH. The resulting crude extract was
      suspended in water and extracted with solvents of different polarities. The
      extracts were evaluated for their cytotoxic effects against Artemia salina and 3
      breast cancer cell lines. RESULTS: About 50% of the extracts evaluated against
      Artemia salina exhibited LC50 values of less than or equal to 200 MUg/mL. The
      strongest activity was detected in the chloroform and ethyl acetate extracts of
      Guaiacum officinale, with lethality values below 10 MUg/mL. The extracts were
      further evaluated for their bioactivity as possible inhibitors of several breast
      cancer cell lines, with the extracts from Simarouba tulae and Croton discolor
      showing the highest percentages of growth inhibition. The dose- effect data
      analysis for the crude extracts of the different plants also confirms the high
      cytotoxicities of Guaiacum officinale, Simarouba tulae, and Croton discolor.
      CONCLUSION: Based on our results, we concluded that the Simarouba, Croton, and
      Guaiacum plant extracts show cytotoxic and anticancer activities that merit
      closer investigation in order to identify the chemical compounds responsible for
      these bioactivities.

PMID- 25856876
TI  - Presence of tissue transglutaminase IgA antibody as a celiac disease marker in a
      sample of patients with irritable bowel syndrome.
AB  - Recent medical literature agrees that celiac disease (CD) is much more prevalent
      in western civilization than it was thought to be in the past. Given the
      potential complications and consequences of untreated CD, screening programs have
      been considered. Symptoms of celiac disease may resemble those of Irritable Bowel
      Syndrome. A group of patients with IBS was screened for CE using the Tissue
      Transglutaminase Antibody IgA serum test. A total of 18 patients were screened.
      All of our patients tested negative for TTG IgA. This finding may indicate that
      the prevalence of CD may be low in our population. Further population studies are
      needed to confirm our finding.

PMID- 25856875
TI  - Measuring health literacy among people living with HIV who attend a community
      based ambulatory clinic in Puerto Rico.
AB  - OBJECTIVE: Health literacy is an important area for interventions aimed at
      reducing or eliminating the health disparities of people living with HIV (PLWH).
      We sought to determine the level of functional health literacy (FHL) and its
      association with medication adherence, symptoms, and their attendant management
      strategies in PLWH. METHODS: This was a cross-sectional study conducted with 200
      adults from a community-based ambulatory clinic in San Juan, Puerto Rico.
      RESULTS: The mean age of the participants was 46.61. Almost half of all
      participants (47%) had marginal or inadequate levels of health literacy (21.5%, n
      = 23; 25.50%, n = 51, respectively). Educational level, being employed, annual
      income, having children, incorrect self-reported CD4+T cell counts, were they
      actually reported their viral loads, adherence to antiretroviral treatment (ART),
      and use of self-care strategies for depression were significantly related to a
      given individual's level of health literacy (p < 0.05). Significant interactions
      were found between adherence and FHL (p = 0.0069). People with marginal health
      literacy had a higher mean score (1.77 +/- 937) on the adherence scale than did
      those with inadequate literacy levels. After adjusting for age, education, and
      the number of people per room at the participant's home, data showed that for
      those who were 45 years of age or younger, there were significant differences (p
      = 0.002) in the mean scores of the adherence scale between those with marginal
      levels of health literacy and those who had inadequate levels of same (5.66 +/-
      1.84). CONCLUSION: Findings from this study fill an existing gap in the important
      area of health literacy among PLWH in Puerto Rico and highlight the importance of
      conducting future research geared towards incorporating FHL as an essential
      component in the management of adherence as well as in both symptoms and the
      management of same in PLWH.

PMID- 25856877
TI  - Sporadic Creutzfeldt-Jakob disease in a native Puerto Rican patient.
AB  - The diagnosis of Creutzfeldt-Jakob disease (CJD) is often a challenge for most
      physicians given its extremely low incidence and different clinico-pathological
      presentations. We report the case of a 56-year old patient native to Puerto Rico
      suspected of sporadic Creutzfeldt-Jakob disease (sCD). The symptoms at onset were
      notorious for bilateral cortical blindness followed by rapidly progressive
      cognitive decline, visual deficit, increased levels of CSF 14-3-3 and tau along
      with positive brain MRI and EEG, are highly indicative of CJD. The definite
      diagnosis was confirmed by the National Prion Disease Pathology Surveillance
      Center (NPDPSC), in Cleveland, Ohio, USA. Lack of genetic mutations in the prion
      protein (PrP) gene, widespread histopathological changes and the accumulation of
      scrapie PrP (PrPSc) in the brain confirmed the diagnosis of sCJD. The patient,
      admitted to our institution in 2011, represents the first detailed report of sCJD
      in a native Puerto Rican patient living in Puerto Rico.

PMID- 25856878
TI  - The night-float system: wider implications.

PMID- 25856879
TI  - Reply: To PMID 24964637.

PMID- 25856880
TI  - [Endemic status of schistosomiasis in People's Republic of China in 2013].
AB  - This report presented the endemic status of schistosomiasis in the People's
      Republic of China at national level in 2013. By the end of 2013, there are 184
      943 schistosomiasis japonica cases. Meanwhile, nine acute cases were reported,
      and 4 cases reduced compared with that of 2012. A total of 29 796 advanced cases
      were reported; while 911 cases were determined as advanced cases and 1 700 cases
      were dead in 2013. Nationally, there were around 365 467.99 hm2 Oncomelania snail
      infested areas in total and 9.25 hm2 of them habituated infected snails in 2013.
      There were 287.28 hm2 of snail infested areas found in non-endemic areas
      historically. Moreover, 962 065 cattle were estimated to be raised in endemic
      regions and 633 cattle were determined as positive by stool examinations. The
      data showed that the endemicity of schistosomiasis in China decreased further.
      However, challenges exist to reach the aims of the medium and long-term national
      program. Further control and effective surveillance need to be strengthened as
      the endemicity of schistosomiasis is unstable in the areas after schistosomiasis
      transmission under control or interruption.

PMID- 25856881
TI  - [Determination of key interventions for the transition from control to
      elimination of malaria in China].
AB  - OBJECTIVE: To determine the key interventions transferring from the control to
      elimination of malaria in China so as to provide the basic information for
      achieving malaria elimination. METHODS: Based on the data collected from the
      document entitled of The National Annual Report on Schistosomiasis, Malaria and
      Echinococcosis, published by the National Institute of Parasitic Diseases of
      Chinese Center for Disease Control and Prevention, the malaria incidence and
      intervention data were selected only in the typical endemic provinces during the
      period of 2004-2010. The correlation between the incidence and interventions in
      the target provinces was analyzed based on the Panel Data Regression Model, and
      the key interventions were determined. RESULTS: Four provinces namely Anhui,
      Yunnan, Hainan and Henan were targeted with 87.56% of the national malaria
      figures from 2004 to 2010. When Y was given as vivax malaria incidence, X1 as the
      log of the number of historical cases receiving radical treatment in the pre
      transmission stage (RTPT) (F = 14.53, P < 0.01, R2 = 0.72), X2 as the log of risk
      population receiving RTPR (F = 15.90, P < 0.01, R2 = 0.71) and X3 as the number
      of technicians trained in microscopy (F = 11.53, P < 0.01, R2 = 0.61), three
      space-fixed effect models were established respectively, and X1, X2, as well as
      X3 had negative effects on Y value. When Y was given as falciparum malaria
      incidence, X1 as the accumulated technicians trained in microscopy (F = 11.06, P
      < 0.01, R2 = 0.87), X2 as the log of technicians trained in entomology (F =
      15.28, P < 0.01, R2 = 0.89) , two two-way (space and time) fixed effect models
      were established respectively, and both X1 and X2 had negative effects on Y
      value. CONCLUSION: RTPT among historical patients and at-risk populations as well
      as microscopy training influences the variation of vivax malaria incidence, while
      the significant interventions of microscopy training and vector control training
      indicate that the integrated measures with strengthened capacity in diagnosis and
      vector control are of importance in the control of falciparum malaria
      transmission.

PMID- 25856882
TI  - [Schistosomiasis control effect of measures of replacing cattle with machine for
      cultivation and forbidding depasturage of livestock on marshlands in marshland
      and lake regions].
AB  - OBJECTIVE: To evaluate the schistosomiasis control effect of the measures of
      replacing cattle with machine for cultivation and forbidding depasturage of
      livestock on marshlands in marshland and lake regions. METHODS: The retrospective
      review and field survey were implemented in the Jiangling and Gongan counties of
      Hubei Province where were implemented with the measure of replacing cattle with
      machine for cultivation, and Yuanjiang and Huarong counties of Hunan Province
      where were implemented with the measure of forbidding the depasturage of
      livestock on marshlands. The schistosome infection status of human, cattle, and
      Oncomelania hupensis snails, and schistosome-infested field excreta were surveyed
      from 2007 to 2013. The effects of the interventions were compared before and
      after their implementations. RESULTS: The 6 villages of Hubei Province were
      implemented with the measure of replacing cattle with machine for cultivation,
      and 7 villages of Hunan Province were implemented with the measure of forbidding
      the depasturage of livestock on marshlands. From 2007 to 2013, the schistosome
      infection rates of residents declined from 3.95% to 0.70% (chi2 = 128.376, P <
      0.05), with the descend range of 82.53%. The descend ranges of the measures of
      replacing cattle with machine for cultivation and forbidding the depasturage of
      livestock on marshlands were 83.081% and 81.62% respectively, and there was no
      significant difference between the two measures (chi2 = 0.132, P > 0.05). The
      infection rate of cattle decreased from 3.66% in 2007 to 0.65% in 2013, and the
      descend range was 82.24% (chi2 = 13.692, P < 0.05). The field excreta was
      surveyed in the snail breeding place in 2013. The investigated area was 157.435
      hm2, and 625 samples of field feces of cattle were collected with the density of
      field excreta of 3.97/hm2, and the positive rate was 1.12% (7/625). The
      schistosome infection rate of snails and the density of infected snails decreased
      successively from 2007, and no infected snails were detected from 2011 to 2013.
      CONCLUSIONS: The schistosomiasis endemic situation are decreased significantly
      after the interventions of replacing cattle with machine for cultivation and
      forbidding the depasturage of livestock on marshlands. Therefore, schistosomiasis
      control effect of these measures is notable in the marshland and lake regions.

PMID- 25856883
TI  - [Further study on possibility of diffusion of Oncomelania hupensis with water in
      river channels of the east route of South-to-North Water Diversion Project].
AB  - OBJECTIVE: To study the drifting law of floats and potential risks of Oncomelania
      hupensis diffusion in the water diversion rivers of the east route of South-to
      North Water Diversion Project. METHODS: The O. hupensis snails in the river
      channels were monitored by the salvage method and snail luring method with rice
      straw curtains, and the diffusion possibility of snails along with water was
      assessed through the drift test of floats with GPS. RESULTS: In the flood seasons
      from 2006 to 2013, totally 8 338.0 kg of floats were salvaged, and 2 100 rice
      straw curtains were put into water in the Li Canal and Jinbao shipping channel,
      but no Oncomelania snails were found. The drift test of floats with GPS before
      water diversion showed that the flow velocity on water surface (northbound) was
      0.45 m/s, the average drift velocity of the floats was 0.56 - 0.60 m/s, and the
      average drift distances each time were 999.70 - 1 995.50 m in the Gaoshui River
      section, while there were no obvious drift in Jinbao shipping channel section.
      During the water diversion period, the flow velocity on water surface
      (northbound) was 0.45 m/s, the average drift velocity of the floats was 0.35 -
      0.41m/s, and the average drift distances each time were 1 248.06 -1 289.44 m in
      the Gaoshui River, while in Jinbao shipping channel section, the flow velocity on
      water surface was 0.28 m/s, the average drift velocity of the floats was 0.25 -
      0.27 m/s, and the average drift distances each time were 477.76 - 496.38 m. The
      drift test showed that the floats gradually closed to the river bank as affected
      by water flow, wind direction and ship waves, when blocked by the reeds, water
      plants or other obstacles, and they would stopped and could not continue to drift
      without outside help. CONCLUSIONS: There are no Oncomelania snails found in the
      river channels of the east route of South-to-North Water Diversion Project. The
      drifting distance of the floating debris along with the water is restricted by
      the flow rate and shore environment.

PMID- 25856884
TI  - [Prediction of epidemic tendency of schistosomiasis with time-series model in
      Hubei Province].
AB  - OBJECTIVE: To study the endemic trend of schistosomiasis japonica in Hubei
      Province, so as to provide the theoretical basis for surveillance and forecasting
      of schistosomiasis. METHODS: The time-series auto regression integrated moving
      average (ARIMA) model was applied to fit the infection rate of residents of Hubei
      Province from 1987 to 2013, and to predict the short-term trend of infection
      rate. RESULTS: The actual values of infection rate of residents were all in the
      95% confidence internals of value predicted by the ARIMA model. The prediction
      showed that the infection rate of residents of Hubei Province would continue to
      decrease slowly. CONCLUSION: The time-series ARIMA model has good prediction
      accuracy, and could be used for the short-term forecasting of schistosomiasis.

PMID- 25856885
TI  - [Efficacy of routinely used patterns for schistosomiasis diagnosis in lake and
      marshland regions].
AB  - OBJECTIVE: To evaluate the efficacy of routinely used pattern for schistosomiasis
      diagnosis in lake and marshland regions. METHODS: A historically heavy endemic
      village of schistosomiasis named Jinggan Village from Jiangling County was
      selected for field survey. The residents aged 6-65 years were screened by
      indirect hemagglutination assay (IHA) and dipstick dye immunoassay (DDIA) in
      parallel. The serological positives were examined by Kato-Katz technique and
      miracidium hatching technique to determine the infection of schistosome. The
      consistency of the two serological methods was evaluated. In addition, the
      schistosome infection rates were estimated accordingto the 3 detection patterns
      namely IHA, DDIA, IHA+DDIA combined with the etiologic examination. RESULTS: A
      total of 530 individuals were examined by the serological tests. The positive
      rate of DDIA was 46.98% (249/530), significantly higher than that of IHA (28.49%,
      151/530) (chi2 = 59.55, P < 0.01). Totally 279 individuals were serological
      positives determined by IHA or DDIA, while 252 of them were detected by stool
      examination, and 22 cases were determined as parasitological positives, while 7
      and 3 cases were diagnosed as antibody negatives by IHA and DDIA, respectively.
      The estimated infection rates determined by IHA, DDIA, IHA plus DDIA combined
      with stool examination were 3.14%, 3.97%, 4.60%, respectively. CONCLUSIONS: Under
      the condition of endemic situation becoming more and more waning, the current
      routinely used pattern for schistosomiasis detection may lead to missed
      diagnosis. So, more sensitive and effective diagnostic tools or appropriate
      detection patterns need to be explored.

PMID- 25856886
TI  - [Surveillance and risk assessment system of schistosomiasis in Jiangsu Province.
      II. Surveillance pattern and effect of Oncomelania hupensis snail status in
      Dongtai City, Jiangsu Province].
AB  - OBJECTIVE: To explore the method of Oncomelania hupensis snail surveillance in
      transmission-interrupted regions of schistosomiasis, so as to provide a new
      pattern for the surveillance of snail status in the transmission-interrupted
      areas. METHODS: In Dongtai County, north of Jiangsu Province where the
      transmission of schistosomiasis was interrupted, the surveillance of snail status
      was performed by means of the village-level general survey, village-level
      sampling survey, snail survey in key settings of township and county, and snail
      reporting by residents. In addition, quality-control snail sites were set up for
      quality control. The effectiveness and cost of the four methods of snail
      surveillance was compared. RESULTS: A total of 163 079 settings and 22 785.62 hm2
      were surveyed in Dongtai County from 2008 to 2013, and 89 residual snail breeding
      sites were found, with a snail area of 1.48 hm2. The patterns of village-level
      general survey, village-level sampling survey, and snail survey in key settings
      of township and county were employed for investigation of 94 550, 45 033 and 23
      496 settings, consisting of 57.98%, 27.61% and 14.41% of total settings, and 2, 0
      and 6 settings were found with snails, with 0.021/thousand, 0, and 0.255/thousand
      detection rates of settings with snail breading sites, respectively. The pattern
      of snail survey in key settings of township and county was more effective than
      that of village-level survey to detect-snail breeding sites (chi2 = 19.158, P =
      0). The recovery rate of quality-control snail breeding sites was 52.56%, 38.27%
      and 73.62% for the three patterns of snail survey, respectively, and the pattern
      of snail survey in key settings of township and county showed a higher quality
      for snail survey than that of village-level survey (chi2 = 111.597 and 85.991,
      both P = 0). During the period from 2008 to 2013, 289 person-times reported 279
      suspected snail habitats and 1 501 living snails, and no Oncomelania snails were
      found. During the 6-year period, there were 1617.5, 964.7 and 527.7 thousand RMB
      invested for village-level general survey, village-level sampling survey, and
      snail survey in key settings of township and county, and the cost of snail survey
      per hm2 was 129.88, 133.6 and 162.57 RMB/hm2, respectively. The cost of village
      level general survey and snail survey in key settings of township and county to
      detect a snail-breeding site was 808 800 and 88 000 RMB, respectively (t =
      12.850, P = 0.000), and the cost of snail survey in key settings of township and
      county was 10.88% of that of village-level general survey. CONCLUSION: The snail
      survey in key settings of township and county is a highly effective and high
      quality method for snail surveillance, which miay serve as a prior way for the
      surveillance of snail status in the transmission-interrupted areas of
      schistosomiasis.

PMID- 25856887
TI  - [Bibliometric analysis of literature regarding integrated schistosomiasis control
      strategy with emphasis on infectious source control].
AB  - OBJECTIVE: To evaluate the outcomes of implementation of integrated
      schistosomiasis control strategy with emphasis on infectious source control using
      a bibliometric method. METHODS: The literature pertaining to integrated
      schistosomiasis control strategy with emphasis on infectious source control was
      retrieved from CNKI, Wanfangdata, VIP, PubMed, Web of Science, BIOSIS and Google
      Scholar, and a bibliometric analysis of literature captured was performed.
      RESULTS: During the period from January 1, 2004 through September 30, 2014, a
      total of 94 publications regarding integrated schistosomiasis control strategy
      with emphasis on infectious source control were captured, including 78 Chinese
      articles (82.98%) and 16 English papers (17.02%). The Chinese literature was
      published in 21 national journals, and Chinese Journal of Schistosomiasis Control
      had the largest number of publications, consisting of 37.23% of total
      publications; 16 English papers were published in 12 international journals, and
      PLoS Neglected Tropical Diseases had the largest number of publications (3
      publications). There were 37 affiliations publishing these 94 articles, and
      National Institute of Parasitic Diseases, Chinese Center for Disease Control and
      Prevention (16 publications), Anhui Institute of Schistosomiasis Control (12
      publications) and Hunan Institute of Schistosomiasis Control (9 publications)
      ranked top three affiliations in number of publications. A total of 157 persons
      were co-authored in these 94 publications, and Wang, Zhou and Zhang ranked top 3
      authors in number of publications. CONCLUSION: The integrated schistosomiasis
      control strategy with emphasis on infectious source control has been widely
      implemented in China, and the achievements obtained from the implementation of
      this strategy should be summarized and transmitted internationally.

PMID- 25856888
TI  - [Preliminary studies on effect of polysaccharides from Tegillarca granosa as an
      adjuvant on DNA vaccine against Schistosoma japonicum infection].
AB  - OBJECTIVE: To discuss the effect of polysaccharides from Tegillarca granosa as an
      adjuvant on pcDNA3.1-Sj26GST vaccine against Schistosoma japonicum infection.
      METHODS: Sixty SPF BALB/c mice were divided into four groups randomly (15 mice
      each group), including a control group, a polysaccharides group, a vaccine group,
      and a vaccine plus polysaccharides group. In the 0, 2th and 4th week of the
      experiment, the mice in the above four groups were immunized for 3 times with 100
      MUl PBS, 100 MUg polysaccharides from Tegillarca granosa, 100 MUg Sj26GST
      vaccine, and 100 MUg Sj26GST vaccine plus equivalent polysaccharides,
      respectively. Two weeks after the last immunization, all the mice were infected
      with 40 +/- 1 Schistosoma japonicum cercariae through the skin of the abdomen.
      After the infection for 6 weeks, all the mice were sacrificed, and their serums,
      livers and the adult worm of Schistosoma japonicum in them were collected, the
      specific sera IgG antibodies were detected by ELISA, and the worm reduction rates
      and egg reduction rates in the liver were calculated. RESULTS: Six weeks after
      the infection, the IgG antibody levels of the mice in the vaccine group and the
      vaccine plus polysaccharides group were 18.26 +/- 0.42 mg/ml and 20.21 +/- 0.89
      mg/ml respectively, the difference between them were statistically significant,
      and both of the IgG levels of the above groups were significantly higher than
      those in the control (both P < 0.05). The worm reduction rate and egg reduction
      rate in the vaccine group were 28.60% and 35.84%, respectively, and the rates in
      the vaccine plus polysaccharides group were 38.04% and 49.74%, respectively, the
      differences between the worm reduction rates and egg reduction rates were both
      statistically significant (both P < 0.05). Meanwhile, the two rates in the two
      above groups were all significantly higher than those in the control group (all P
      < 0.01). CONCLUSION: Polysaccharides from Tegillarca granosa using as an adjuvant
      can increase the protection effect of pcDNA3.1-Sj26GST vaccine against
      Schistosoma japonicum infection.

PMID- 25856890
TI  - [Cloning, expression and bioinformatics analysis of cathepsin B of Echinococcus
      granulosus].
AB  - OBJECTIVE: To clone and express cathepsin B gene of Echinococcus granulosus
      (EgCatB) and analyze EgCatB protein by using bioinformatics tools and online
      databases. METHODS: The total RNA of E. granulosus was extracted and reversely
      transcribed into cDNA as the template sequence for PCR. The EgCatB gene was
      cloned by using the In-Fusion PCR cloning method and expressed by a wheat germ
      cell-free system, and then the recombinant protein was identified by Western
      blotting. The signal peptide, transmembrane helices and subcellular location of
      the EgCatB sequence were predicted by the online software SignalP 4.1, TMHMM
      sever v. 2.0 and TargetP 1.1 respectively. Subsequently, the homologue sequence
      and conserved sites were aligned by using BLASTP and GeneDoc software. Finally,
      the structures and the glycosylation modification site of the EgCatB encoding
      protein were analyzed and predicted in turn by ProtParam, SMART, Predictprotein,
      Swiss-model, NetOGlyc 4.0 and NetNGlyc 1.0 approaches. RESULTS: The EgCatB gene
      was successfully amplified from cDNA of E. granulosus and expressed in the
      soluble fractions. The molecular weight of the expressed protein was estimated 35
      kDa. The bioinformatics analysis revealed that EgCatB was a classical secreted
      protein containing a Pept_C1 domain. The homology analysis indicated that the
      amino acid sequence of EgCatB was highly conserved in the active enzyme sites.
      The protein structure prediction showed a catalytic active center was formed
      through Gln106, Cys112, His282 and Asn302. It was found that there were nine O
      glycosylation sites in the EgCatB sequence, but no N-glycosylation sites.
      CONCLUSIONS: The EgCatB gene is cloned and expressed successfully, and the
      recombinant protein is analyzed by bioinformatics approaches and structure
      predication. The study provides useful information for further functional study
      of the EgCatB protein.

PMID- 25856889
TI  - [Distribution characteristics of deposited eggs and pathological changes in
      viscera of New Zealand white rabbits infected with Schistosoma japonicum at
      different time].
AB  - OBJECTIVE: To study the distribution characteristics of deposited eggs and
      pathological changes in the viscera of animal infected with Schistosoma japonicum
      at different time. METHODS: New Zealand white rabbits were infected artificially
      with quantitative S. japonicum miracidia, then the distribution characteristics
      and the hatchability of schistosome eggs as well as the pathological changes of
      the corresponding viscera of the rabbits 42 and 60 d post-infection were observed
      and compared. RESULTS: On the 42nd day post-infection, among all the viscera
      observed, the percentage of eggs deposited, the number of eggs per gram and the
      hatchability were the highest in the liver, while on the 60th day post-infection,
      the tissues and organs with the highest values of the above 3 indexes were the
      liver, rectum and upper section of the small intestine, respectively. From 42 day
      to 60 day post-infection, the liver of infected rabbits became swelling,
      hardening and lost elasticity, the color changed from black to dark grey, and egg
      nodules gradually appeared in the different sections of the small intestine, and
      also the mucosal hyperemia, edema and egg nodules were seen in the colon, cecum
      and rectum. The lesion levels tended to be correlated with the deposition of
      eggs. CONCLUSION: The amount and the density as well as the hatching rate of
      deposited eggs of S. japonicum in the viscera of infected rabbits at different
      time are different, and the lesion level in the host is correlated with the
      deposition of eggs.

PMID- 25856891
TI  - [Effect of Lep d2 from Lepidoglyphus destructor as a vaccine for specific
      immunotherapy in murine with asthma].
AB  - OBJECTIVE: To assess the effect of Lep d2 from Lepidoglyphus destructor as a
      vaccine for specific immunotherapy on murine model of asthma. METHODS: Thirty
      BALB/c mice (SPF) were randomly categorized into a PBS group, an asthma group,
      and a Lep d2 SIT group. The mice in the asthma group and Lep d2 SIT group were
      sensitized by intraperitoneal injection with extracts of dust mites on Days 0,
      7th, and 14th, while those in the PBS group were injected with PBS. From the 21st
      day, the asthma group and Lep d2 SIT group exposed to the extracts of dust mites
      were stimulated by aerosol inhalation for 7 successive days. During the period of
      the 25th-27th Day, the mice in Lep d2 SIT group were injected intraperitoneally
      with Lep d2 allergen for SIT 30 min before nasal inhalation, whereas the PBS
      group and asthma group were treated with only PBS. Twenty-four hours after the
      final inhalation, all the mice were sacrificed, the bronchoalveolar lavage fluids
      (BALFs) were collected. The levels of IFN-gamma, IL-5 and IL-13 in the BALF and
      the supernatant of splenocyte culture solution (SSCS) as well as the levels of
      specific IgE (sIgE) and sIgG2a in the sera were detected by ELISA. The lung
      tissues of the mice in the above 3 groups were stained by haematoxylin and eosin
      (H&E) and observed by a microscope. RESULTS: The symptoms of acute asthma attack
      were observed in the mice of the asthma group and Lep d2 group, but not in the
      PBS group. The allergic inflammation changes in lung in the Lep d2 SIT group were
      significantly alleviated compared with those in the asthma group. The
      concentrations of IFN-gamma in BALFs and SSCS of the mice in the Lep d2 SIT group
      were significantly higher than those in the asthma group (both P < 0.01), while
      the levels of IL-5 and IL-13 in the former group were significantly lower than
      those in the latter group (all P < 0.01). Meanwhile, the level of sIgE of mice in
      the Lep d2 SIT group was significantly lower than those in the asthma group (P <
      0.01), while the level of sIgG2a of mice in the former group was higher than
      those in the latter group (P < 0.01). CONCLUSION: Lep d2 allergen as a vaccine
      can alleviate the allergic symptoms in the lung of mice effectively after
      allergen specific immunotherapy.

PMID- 25856892
TI  - [Study on biological characteristics of cypermethrin-resistant and -susceptible
      strains of Aedes albopictus at different temperatures].
AB  - OBJECTIVE: To study the biological characteristics of cypermethrin-resistance
      strain and -susceptible strain of Aedes albopictus under different controlled
      temperatures in the laboratory. METHODS: The two strains were raised at three
      different temperatures, 20, 25 degrees C and 28 degrees C respectively, and the
      biological characteristics of the two mosquito strains, such as reproduction,
      development and life expectancy, were observed and recorded in the laboratory.
      RESULTS: The life expectancy of both strains became shorter as the temperature
      raised, and the resistant strain(69.37% +/- 0.01%, 77.04% +/- 0.07%) lived
      shorter than the susceptible strain(85.24% +/- 0.03%, 88.23% +/- 0.05%)in
      average. Under 25 degrees C, the hatching rate of resistant strain decreased by
      25.88%, and the pupation rate decreased by 11.18%. In the three temperatures, all
      the life expectancy expanded as the temperature went up, the periods for the
      susceptible strain were 19.75 +/- 0.10, 23.65 +/- 0.07 d and 25.08 +/- 0.08 d
      under 28, 25 degrees C and 20 degrees C. While life expectancy for the resistant
      strain decreased to 17.21 +/- 0.09, 20.95 +/- 0.09, 22.58 +/- 0.10 d. Under the
      same temperature, the development timing of the resistance strain was longer than
      that of the susceptible strain, and the period was the longest under 28 degrees C
      (156.2 h, 137.1 h). In the three temperatures, all the development periods
      expanded as the temperature went up, the susceptible and resistant larvae
      developed 137.1 d and 163.3 d, 247.7 d and 156.2 d, 182.3 d and 263.2 d under 28,
      25 degrees C and 20 degrees C. The differences show statistic significance (P <
      0.05). CONCLUSION: The resistance of A. albopictus to cypermethrin results in the
      decrease of adaptability to the environment change and the disadvantage of
      reproduction at different temperatures.

PMID- 25856893
TI  - [Isolation and identification of Toxoplasma gondii strains from cats in Xuzhou
      region].
AB  - OBJECTIVE: To isolate Toxoplasma gondii (T. gondii) strains from stray cats and
      explore their prevalence in Xuzhou City. METHODS: The sera of 41 stray cats were
      collected to detect the antibodies of T. gondii by using a commercial enzyme
      linked immunosorbent (ELISA) kit. The tissues including the heart, brain and
      tongue from these cats were digested by acid pepsin solution and inoculated to
      Kunming mice. These suspicious isolates were subsequently identified by a
      specific PCR method. RESULTS: A total of 11 strains were isolated from 41 stray
      cats, which were confirmed by the PCR results. Moreover, 17 cats (41.5%) were
      found to be positive with the antibodies of T. gondii. CONCLUSION: A high
      prevalence of T. gondii infection was found in Xuzhou City, which indicates that
      the stray cats infected with T. gondii would be an important infection source
      that may infect humans and other animals in this area.

PMID- 25856894
TI  - [Effect of comprehensive schistosomiasis control strategy based on infection
      source control in Hanchuan City].
AB  - OBJECTIVE: To evaluate the effect of comprehensive schistosomiasis control
      measures based on infection source control in Hanchuan City (marshland and lake
      endemic regions). METHODS: The data of comprehensive schistosomiasis control in
      Hanchuan City from 2004 to 2013 were collected, and the change trends of the
      Oncomelania hupensis snail status and the infection situation of human and
      livestock were analyzed to evaluate the control effect. RESULTS: After the
      implementation of the comprehensive measures, the infection rates of residents
      and cattle decreased from 6.38% and 8.11% in 2004 to 0.16% and 0 in 2013
      respectively. There were no acute schistosomiasis patients since 2007, no new
      infection cases since 2011, and no infected snails since 2012. Compared with
      2004, the occurrence rate of frames with living snails and the average density of
      living snails decreased by 56.78% and 68.35%, respectively, but the snail area
      and susceptible area increased by 0.62% and 7.10%, respectively. In 2013, all the
      367 endemic villages in 26 townships reached the criteria of transmission
      controlled. CONCLUSIONS: The comprehensive schistosomiasis control measures based
      on infection source control can control the schistosomiasis transmission
      effectively in marshland and lake endemic regions. When consolidating the
      achievement, the snail area in inner embankment should be compressed to prevent
      the schistosome re-infection in human and livestock.

PMID- 25856895
TI  - [Design and application of psychological intervention paths for ascites type of
      advanced schistosomiasis patients].
AB  - OBJECTIVE: To explore the design and application of psychological intervention
      paths for ascites type of advanced schistosomiasis patients. METHODS: A total of
      156 ascites type of advanced schistosomiasis patients were divided into an
      intervention group and a control group with 78 cases each. A psychological
      intervention path table was designed in accordance with the psychological
      characteristics and demands of the advanced schistosomiasis patients. Five steps
      were used to guide the nurses involved to carry out the psychological
      intervention. RESULTS: Before the intervention, there were no statistically
      significant differences (all P > 0.05) between two groups in SAS, SDS, WHOQOL
      BRER scores, but after the intervention, all the evaluation indexes improved in
      the intervention group and there were statistically significant differences
      between the intervention group and control group in SAS, SDS, WHOQOL-BRER scores
      (all P < 0.05). CONCLUSION: The application of psychological intervention paths
      for ascites type of advanced schistosomiasis patients can improve their negative
      emotions and qualities of life.

PMID- 25856896
TI  - [Effect of comprehensive prevention and control of soil-transmitted nematodiasis
      in Runzhou District of Zhenjiang City].
AB  - OBJECTIVE: To evaluate the effect of comprehensive prevention and control of soil
      transmitted nematodiasis in Runzhou District, Zhenjiang City, Jiangsu Province
      from 1997 to 2012. METHODS: The comprehensive prevention and control measures
      included the helminthicide, health education, improvement of water supplier and
      harmless toilets, and these measures were implemented continuously. At the same
      time, the infection rates of soil-transmitted nematodes, the local economic
      indicators, and the coverage rates of tap water and harmless toilets were
      surveyed. RESULTS: The mass chemotherapy was performed for 202 100 person-times
      and the diagnosed chemotherapy was performed for 2 006 person-times in Runzhou
      District from 1997 to 2012. The awareness rates of health knowledge were 57.18%
      in 1997, and 95.62% in 2012. The coverage rates of tap water and harmless toilets
      were 10.14% and 10.21% in 1997, and 100.0% and 90.38% in 2012, respectively.
      There were negative correlations between the awareness rate of per capita GDP,
      per capita net income, coverage rates of tap water, coverage rates of harmless
      toilets, health knowledge and the infection rate of soil-transmitted nematodes,
      respectively (r(per capitaGDP) = -0.526, P < 0.05; r(per capita net income) = 
      0.671, P < 0.01; r(coverage rates of tap water) = -0.936, P < 0.01; r(coverage
      rates of harmless toilets) = -0.922, P < 0.01; r(awareness) = -0.774, P < 0.01).
      The statistical analysis showed that the infection rate of soil-transmitted
      nematodes had a downward trend as an exponential curve in Runzhou District from
      1997 to 2012 (y = 42.031 7e(-0.357 6x), R2 = 0.803 6, F = 57.28, P = 0.000). The
      infection rate of degradation by an annual rate was 29.18%. The infection rate in
      farmers was significantly higher than that in students (chi2 = 17.998, P < 0.01).
      There was no significant difference between men and women in the infection rate
      of soil-transmitted nematodes (chi2 = 3.627, P = 0.057). CONCLUSION: The
      comprehensive prevention and control measures and the development of social
      economy contribute to the steady decline of soil-transmitted nematode infections.

PMID- 25856897
TI  - [Therapeutic effect of 138 imported falciparum malaria patients].
AB  - OBJECTIVES: To summarize the clinical characteristics of imported falciparum
      malaria patients and the treatment, so as to provide the evidences for improving
      the diagnosis and treatment of the disease. METHODS: A total of 138 imported
      falciparum malaria patients who received the treatment in Shandong Institute of
      Parasitic Diseases from January 2007 to February 2013 were adopted as the
      observation subjects, and their clinical data were collected and analyzed.
      RESULTS: All the 138 patients were back from African countries. The main
      manifestations were fever, headache, asthenia, and hepatosplenomegaly, and most
      of them were with decreased RBC, PLT levels and increased LDH levels, and 36.96%
      of them were misdiagnosed as respiratory diseases, nephritis, hepatitis and so
      on. Through antimalarial treatment of artemether or artesunate or
      dihydroartemisinin and primaquine, or dihydroartemisinin and piperaquine, and
      symptomatic treatment, the short-term and long-term cure rates were 98.55% and
      94.93% respectively, with 1 case unrecovered and 1 died. CONCLUSIONS:
      Artemisinins are still the most effective antimalarial drugs for falciparum
      malaria. However, some patients recrudesce as the Plasmodium in their body is
      resistant or insensitive to these drugs. We should pay more attention to the
      antimalarial and symptomatic treatments in the early stage of severe malaria so
      as to improve the cure rate.

PMID- 25856898
TI  - [Presumptive role of Wolbachia in deltamethrin resistance of Culex pipiens
      pallens].
AB  - OBJECTIVE: To investigate the relationship between Wolbachia and deltamethrin
      resistance in Culex pipiens pallens. METHODS: PCR was used to detect Wolbachia in
      Culex pipiens pallens and qRT-PCR was performed to determine and compare the
      expression of Wolbachia between deltamethrin- resistant and - susceptible strains
      of Culex pipiens pallens. RESULTS: Wolbachia was detected in Culex pipiens
      pallens in the laboratory. The expression of Wolbachia was 18.42, 3.69, 4.43,
      3.96, 6.31, 1.55 and 3.76 folds higher in the deltamethrin-resistant strain than
      in susceptible strain in the egg, 1st, 2nd, 3rd, 4th stages, and male and female
      adults, but there was no statistical difference in the pupae stage. The
      expression of Wolbachia was 2.64 folds higher in deltamethrin-resistant females
      than in susceptible females which were caught in Jiangxinzhou of Nanjing.
      CONCLUSION: Wolbachia is associated with deltamethrin resistance in Culex pipines
      pallens.

PMID- 25856899
TI  - [Observation of animal model of life cycle of Angiostrongylus cantonensis].
AB  - OBJECTIVE: To observe the effect of artificially construction of the life cycle
      of Angiostrongylus cantonensis in the laboratory condition, so as to provide the
      basis for the research of angiostrongyliasis. METHODS: SD rats were infected
      orally with the third-stage larvae of A. cantonensis collected from infected
      Pomacea canaliculata. Six weeks after the infection, the first-stage larvae were
      isolated and counted from fresh feces of the rats and then were used to infect P.
      canaliculata. Three weeks later, the snails were dissected for counting the third
      staged larvae of A. cantonensis. RESULTS: The first-stage larvae were detected in
      the feces of the rats 6 weeks after the infection, and the third-staged larvae
      were successfully isolated after the infection of P. canaliculata. CONCLUSION:
      The animal model of the entire life cycle of A. cantonensis is successfully
      established in the laboratory with the infection of 50 larvae per rat.

PMID- 25856900
TI  - [Four alien medical mollusk found in Dapeng Peninsula, Shenzhen City].
AB  - OBJECTIVE: To investigate the alien snails in Dapeng Peninsula, Shenzhen City.
      METHODS: The survey on the snail diversity in Dapeng Peninsula was carried out
      from August 2012 to Jan 2013, and the species of the alien snails were identified
      according to the shell morphology. RESULTS: Four species of alien snails
      including Achatinafulica, Pomacea canaliculata, Physa acuta, and Biomphalaria
      straminea were found in Dapeng Peninsula, P. acuta was found in all of the
      collected sites, A. fulica and P. canaliculata were distributed in five regions
      except Yangmeikeng area, and B. straminea was just found in Dapeng Town.
      CONCLUSION: Four species of important alien snails invade widely in Dapeng
      Peninsula, Shenzhen City. As their potential risk to the disease transmission and
      agriculture production, the relative departments should strengthen the control
      and prevention.

PMID- 25856901
TI  - [Research on competency building standards of institutions of schistosomiasis
      prevention and control in Hubei Province. II. Investigation of human resources].
AB  - OBJECTIVE: To understand the human resources of the grassroots institutions of
      schistosomiasis control and prevention, so as to provide the evidence for
      formulating the standards of institutional capacity-building. METHODS: By using
      the combination of quantitative and qualitative methods, the hierarchy of
      schistosomiasis control institution workers, structural features of workers, and
      benefits of workers were investigated and the results were analyzed statistically
      after the 2004 reform. RESULTS: The constituent ratios of personnel <= 30 years
      old, 30 to 45 years old, and >= 45 years old were 6.8%, 64.0% and 29.2%
      respectively, with an average age of 43.1 years. For education levels, 61.35% of
      the personnel had secondary or high school levels. At the city level, the
      structural proportion of the senior professional; medium professional and primary
      professional titles was 1.4 : 5.6 : 3.0, and at the county level, the proportion
      was 0.5 : 6.1 : 3.4. There was 14 200 yuan per capita at the township
      schistosomiasis control institutions. CONCLUSION: The technology of the personnel
      in schistosomiasis institutions of Hubei Province is weak, the average age of
      personnel is old, and the salary is low.

PMID- 25856902
TI  - [Analysis of citing journals and cited journals of 3 core parasitological
      journals].
AB  - OBJECTIVE: To understand the achievement exchange and interpenetration situation
      between parasitological journals and the journals of other disciplines. METHODS:
      The citing journals and cited journals of Chinese parasitological journals were
      analyzed. Three Chinese core journals, namely Chinese Journal of Parasitology and
      Parasitic Diseases, Chinese Journal of Schistosomiasis Control, and Chinese
      Journal of Zoonoses, were selected as the study objects. The number and citation
      times of citing and cited journals from 2002 to 2012 were collected from CNKI.
      These journals were classified according to China Journal Citation Reports-Expand
      (2013), and analyzed by the method of bibliometrics. RESULTS: The number of
      published papers in Chinese Journal of Parasitology and Parasitic Diseases,
      Chinese Journal of Schistosomiasis Control, and Chinese Journal of Zoonoses were
      1 160, 1 541 and 2 494 from 2002 to 2012, respectively. The numbers of citing
      journals of the 3 above journals included by the citation reports were 496, 547
      and 592, respectively, the total citation frequencies were 4 778, 9 547 and 8
      301, and the average citation frequencies per paper were 4.12, 6.20 and 3.33,
      respectively. The numbers of the cited journals were 532, 407 and 659,
      respectively, the total citation frequencies were 4 470, 7 206 and 7 885, and the
      average citation frequencies per paper were 3.85, 4.68 and 3.16, respectively.
      The top three disciplines of the citing journals and cited journals were medical
      and health, basic science, and agricultural sciences, and the top three secondary
      disciplines belonged to medical and health were general medical and health,
      preventive medicine and hygiene, and clinical medicine. CONCLUSION: There is an
      extensive exchange between parasitology journals and other journals, which
      promotes the exchange between parasitology and other relevant disciplines.

PMID- 25856903
TI  - [Study and application of surface antigen in tachyzoites of Toxoplasma gondii].
AB  - Toxoplasma gondii is an intracellular protozoan parasite that infects all warm
      blooded animals. The surface antigens of T. gondii with the potential for
      application as antigens of diagnosis and vaccines have been studied extensively
      in recent years, especially for P43, P35, P30, P23 and P22. The studies on the
      surface antigen in tachyzoites of T. gondii are reviewed in this paper.

PMID- 25856904
TI  - [Evaluation of comprehensive measures of schistosomiasis control in Caidian
      District, Wuhan City].
AB  - OBJECTIVE: To evaluate the implementation and effectiveness of comprehensive
      control measures of schistosomiasis in Caidian District, Wuhan City. METHODS: The
      data of implementation of the schistosomiasis control measures in Caidian
      District was collected and analyzed statistically. RESULTS: The number of
      Oncomelania hupensis snail environments and snail area decreased from 213 sites
      and 223.47 hm2 in 2003 to 59 sites and 51.20 hm2 in 2013, with the decreasing
      rate of 72.30% and 77.09%, respectively. The infection rate of schistosomiasis of
      human decreased from 1.58% in 2006 to 0.24% in 2013, with the decreasing rate of
      84.81%. The positive rate of stool tests of cattle was 2.19% in 2006 while it was
      0 in 2013. CONCLUSION: The comprehensive control measures of schistosomiasis are
      effective.

PMID- 25856905
TI  - [Investigation on current status of advanced schistosomiasis in Shanggao County].
AB  - OBJECTIVE: To understand the current status of advanced schistosomiasis patients,
      so as to provide the reference for improving the medical care of them in Shanggao
      County. METHODS: The data of advanced patients in Shanggao County were collected
      from the Information Management System for the Advanced Schistosomiasis
      Chemotherapy and Assistance in Jiangxi Province, and a field survey including the
      epidemiological investigation, physical examinations, and B ultrasound
      examinations was performed in 2014. All the data were analyzed statistically and
      compared with those in 2010. RESULTS: Among the 128 advanced schistosomiasis
      patients, the male:female ratio was 2.46: 1, the average age was 68.02 +/- 6.19
      years, and the patients older than 65 years contributed to 64.84% for the all.
      The proportions of clinically types of ascites, splenomegaly, multiple granuloma
      in the colon, dwarf, general, and haemorrhage were 57.81%, 12.50%, 2.34%, 0,
      26.57%, and 0.78%, respectively. The ultrasound examinations revealed the average
      diameter of the main trunk of portal vein was 12.70 +/- 1.91mm in 2014, which was
      significantly broader than that of 12.05 +/- 0.34mm in 2010 (P < 0.01).
      CONCLUSIONS: The advanced schistosomiasis patents in Shanggao County decreases
      with years and shows an aging trend. Some advanced schistosomiasis patients are
      worse; therefore the chemotherapy and salvation work still should be
      strengthened.

PMID- 25856906
TI  - [Diagnosis and treatment of cerebral schistosomiasis: a report of 166 cases].
AB  - OBJECTIVE: To discuss the clinical features, diagnosis and treatment of cerebral
      schistosomiasis. METHODS: A total of 166 patients with cerebral schistosomiasis
      were treated, and their clinical data were collected and analyzed
      retrospectively. RESULTS: In 166 cases of cerebral schistosomiasis, the
      confirmative diagnoses of 156 cases were diagnosed according to the clinical
      manifestation, etiology, immunology and auxiliary examination (CT, MRI). In
      among, 74 cases were confirmed by pathological examination, 10 cases were
      diagnosed through to the diagnostic treatment. Totally 102 patients received the
      oral medication of praziquantel, and they all improved and discharged 14-16 days
      later; 64 patients received the craniotomy and praziquantel medication after the
      operation, and 48 patients significantly improved, others did not improve or
      aggravated. There was no operative mortality. CONCLUSIONS: Neuroimaging and
      laboratory tests are valuable in the diagnosis of cerebral schistosomiasis. The
      praziquantel treatment is selected firstly when the diagnosis was established.
      However, in the case of serious intracranial hypertension, intractable epilepsy
      and praziquantel treatment fails, the surgical treatment is required.

PMID- 25856907
TI  - [Analysis of schistosomiasis endemic situation in Jiangling County from 2004 to
      2013].
AB  - OBJECTIVE: To analyze the schistosomiasis endemic situation and understand its
      transmission trend in Jiangling County from 2004 to 2013, so as to improving the
      schistosomiasis control. METHODS: The relevant data of schistosomiasis were
      collected and analyzed statistically in Jiangling county from 2004-2013. RESULTS:
      The human prevalence of schistosomiasis was decreased from 10.22% in 2004 to
      0.63% in 2013 with the descend rate of 93.84%, and the notable descend rate was
      76.92% from 2009-2013. The cattle infection rate was decreased yearly from 7.59%
      in 2004 to 0 in 2013. The appearance rate of frames with living Oncomelania
      hupensis snails and the infection rate of snails reduce by 17.53% and 100%
      respectively. CONCLUSIONS: After 10-year control, the endemic situation of
      schistosomiasis in Jiangling County decreases and is at a low level. However, the
      risk factors of transmission still exist. Therefore, the comprehensive control
      measures still should be enhanced continuously.

PMID- 25856908
TI  - [Investigation on Clonorchis sinensis infection and its risk factors in Futian
      District, Shenzhen City].
AB  - OBJECTIVE: To understand the status of Clonorchis sinensis infection and its risk
      factors in Futian District, Shenzhen City, so as to provide the evidence for
      formulating the strategy of prevention and control. METHODS: Two monitoring
      points were randomly selected, and the permanent population aged >= 3 years were
      investigated and their stool samples were detected for the eggs of C. sinensis by
      using Kato-Katz technique. Meanwhile, the risk factors of infection were also
      investigated. RESULTS: A total of 743 subjects were examined, and 7 persons were
      infected with C. sinensis and the infection rate was 0.94%. Most of the infected
      cases were focused on 20-40 and 40-60 age groups. The risk factors were eating
      raw or semi-cooked fish, and the protective factor was the use of separated
      cutting board for cooked or uncooked food. CONCLUSION: The infection rate of C.
      sinensis is low in the population of Futian District. However, the health
      education, especially for diet health education, still should be strengthened.

PMID- 25856909
TI  - [Surveillance of intestinal helminthiasis in Dafeng City from 2005 to 2010].
AB  - OBJECTIVE: To understand the current status of intestinal helminth infections in
      Dafeng City. METHODS: The residents in 5 villages of Dafeng City were
      investigated, and their stool samples were detected for the eggs of helminth with
      Kato-Katz technique, and Enterobius vermicularis was detected by the cellophane
      anal swab method. RESULTS: The total infection rates of intestinal helminth were
      5.77%, 5.51%, 4.60%, 4.18%, 3.41%, and 1.38% from 2005 to 2010, respectively. The
      trend of total infection rates declined year by year. The infection rates in the
      20-30 age-group and 60-80 age-group were higher than those in other age-groups.
      The infection rates of the male and female were 5.63% (359/6 375) and 2.42%
      (144/5 949), respectively, and there was a significant difference (chi2 = 74.81,
      P = 0.00). The infection rate (11.70%) in the northern areas of Dafeng City was
      higher than that in other places, and the trend of the infection rates decreased
      from the eastern and northern to the western and southern. The infection rate of
      E. vermicularis was 1.75% in children in 2010. CONCLUSIONS: The infection rate of
      intestinal helminth is low, but E. vermicularis infection is relatively general
      in the children in Dafeng City. Therefore, the prevention and treatment still
      need to be strengthened.

PMID- 25856910
TI  - No STEMI left behind.

PMID- 25856912
TI  - Aetiopathogenesis of type-2 diabetes mellitus: could chronic stress play an
      important role?
AB  - OBJECTIVES: Pathogenesis of type-2 diabetes remains elusive. Various factors
      including diet, physical exercise, obesity, genetic factors and stress, have been
      discussed. Among these factors role of stress is still poorly understood in
      diabetes. Therefore the study was planned to assess effect of stress in diabetic
      and non-diabetic population in a comparative descriptive manner. METHODS: 1000
      diabetic cases (group A) and equal number of healthy individuals were selected as
      a comparison group (group B). Both groups were examined at 0, 12, 24 months. To
      assess stress 17 points were examined (factors mainly related to emotions,
      hurriedness, relaxed status etc.), total 68 points for stress were given; > 30/68
      was considered as severe stress. Mental health life style factors like duration
      of sleep and working mental hours were also examined. EEG and SSR were done at 24
      months to assess stress and sympathetic response. RESULTS: There was presence of
      chronic stress, (> 90% had > 30/68 scoring) more mental work and less sleep
      duration in group A. EEG showed synchronised v/s desynchronised basal rhythm in
      group B v/s group A. SSR suggestive of increased sympathetic activity in group A.
      CONCLUSION: It is concluded that chronic stress leads to increased basal
      sympathetic activity, resulting from disturbed cortical hypothalamic axis,
      leading to central insulin resistance and diabetes.

PMID- 25856913
TI  - Outbreak of scrub typhus in Andhra Pradesh--experience at a tertiary care
      hospital.
AB  - AIM: To describe the clinical features, laboratory manifestations, complications
      in patients diagnosed with scrub typhus at a tertiary care hospital in south
      India. MATERIAL AND METHODS: All cases of acute onset fever diagnosed to have
      scrub typhus August 2011 to December 2012 were analysed. Cases of scrub typhus
      confirmed by the well felix test with a titre of 1 in 80 or more and a positive
      immunochromatography test were studied. RESULTS: 176 confirmed cases of scrub
      typhus were studied over a period of 18 months. Majority (96%) of patients are
      from rural background. Farmers constituted 60% of the patients. Most common
      symptoms were due to the involvement of respiratory tract in the form of cough in
      94 (53%) patients followed by breathlessness in 84 (47.7%). Signs of
      consolidation were seen in 80 (45.5%). Central nervous system involvement in the
      form of altered sensorium was seen in 43 (24.4%) and seizures in 11 (6.3%)
      patients. Eshcar was seen in 23 (13%) patients. Transaminases were elevated in
      153 (86%) patients, serum alkaline phosphatase in 110 (62.5%) patients. Renal
      failure was seen in 49 (27.8%) cases and respiratory failure was seen in 11
      (6.2%). Eight (4.5%) patients died in our study. CONCLUSION: Scrub typhus should
      be suspected in patients with rural background with fever and multi system
      involvement. The predominant symptoms were cough and breathlessness. Central
      nervous system abnormalities in the form of altered sensorium was seen in 43
      (24.4%). Most common laboratory abnormality noted in our patients with scrub
      typhus was elevated liver enzymes which were seen in 153 (86%) cases.

PMID- 25856914
TI  - 'The spectrum of vascular dementia'--a retrospective study from South India.
AB  - OBJECTIVES: Vascular dementia (VaD) is high in Indian population and is
      preventable to some extent but there is paucity of literature. Hence we decided
      to study the clinical and laboratory spectrum of VaD. METHODS: It was
      retrospective hospital based study. The patients who satisfied Diagnostic and
      Statistical Manual of Mental Disorders, 4th Edition (DSM-IV criteria) for VaD and
      age of more than 40 years were identified on the basis of case file code which is
      uniformly used by the hospital. RESULTS: Of the 83 patients included, 72.3% (60)
      were males (mean age: 65.3 +/- 8.6 years) and 27.3% (23) females (mean age: 65.7
      +/- 1.1 years). Mean age of the patients was 65.4 +/- 9.2 years. Abrupt onset was
      seen in 42 (51%) patients and 41 (49%) had insidious onset. There was gradual
      progression in 48 (57.8%), stepwise progression in 33 (39.8%) and 2 patients had
      rapid progression. Naming impairment was seen in 64 (77.1%), visuospatial
      disorientation was present in 49 (59%), dyscalculia in 55 (66.3%), emotional
      lability in 26.5%. Hypertension was the single most important risk factor (71.1%)
      followed by smoking (46.9%) and dyslipidaemia (45.8%). Neuropsychological testing
      showed Executive function involvement in 18 (66.7%) followed by memory in 16
      (59.3%) patients. The total white matter hyperintensity score (12.39 +/- 6.73)
      significantly correlated with mini mental scores (r: -0.4; p: 0.02). CONCLUSION:
      We found that in our patients with vascular dementia, gradual progression, naming
      impairment and small vessel disease in imaging were the most common
      abnormalities. Hypertension was the single most important risk factor.

PMID- 25856915
TI  - Prevalence of micro and macrovascular complications and their risk factors in
      type-2 diabetes mellitus.
AB  - OBJECTIVES: To determine the prevalence of micro and macrovascular complications
      in type-2 diabetes in Northwest India and its correlation with various risk
      factors. METHODS: In this study, total 11,157 subjects (M:F 6661:4496), attending
      the diabetic clinic, were analysed. The study sample resembles the population
      sample in anthropometric, age and socioeconomic factors. All patients had
      undergone the test for retinopathy by fundus examination, nephropathy by
      microalbuminuria, serum creatinine and blood urea, neuropathy by monofilament and
      biothesiometer, peripheral vascular disease (PVD) by colour doppler and
      cardiovascular disease by ECG. RESULTS: Among 11,157 subjects, retinopathy was
      diagnosed in 32.5%, nephropathy was present in 30.2%, peripheral neuropathy was
      present in 26.8%, coronary heart disease (CHD) was present in 25.8% and
      peripheral vascular disease (PVD) was present in 28% of the subjects. Multiple
      logistic regression analyses showed that age had a significant association with
      retinopathy, neuropathy, coronary heart disease (CHD) and peripheral vascular
      diseases (PVD). Duration of diabetes had significant association with the
      neuropathy, nephropathy and PVD. Higher HbA1C increases the risk of retinopathy,
      neuropathy and nephropathy. Hypertension was associated with nephropathy and
      coronary heart disease. CONCLUSION: The study highlights the high prevalence of
      vascular complications in type-2 diabetes in Northwest India. Retinopathy and
      nephropathy were the commonest complications of diabetes in our study.

PMID- 25856911
TI  - 2013 consensus statement for early reperfusion and pharmaco-invasive approach in
      patients presenting with chest pain diagnosed as STEMI (ST elevation myocardial
      infarction) in an Indian setting.
AB  - In India, the prevalence of ST elevation myocardial infarction (STEMI) is rising
      exponentially leading to cardiovascular morbidity and mortality. Despite
      advancement in reperfusion therapy (pharmacologic and interventional), the
      overall utilization, system of care and timely reperfusion remains suboptimal.
      JUSTIFICATION AND PURPOSE: Alarming treatment delays exist in patients presenting
      with chest pain observed in real-world and published evidences. Time to diagnose
      STEMI and initiation of reperfusion therapy at various first medical contacts in
      India is variable mandating immediate attention. We intend to provide evidence
      based explicit recommendations for practicing clinicians about time-dependent
      early management and the concept of pharmaco-invasive (PI) approach,
      contextualized to the situation in India. PROCESS: Pre-prepared guidance document
      by expert steering committee was discussed and commented by over 150 experts
      representing from 16 states in India at regional level. The moderators of these
      meetings arrived at a consensus on the evaluation and management of STEMI
      patients by PI approach to improve clinical outcomes. RECOMMENDATIONS: In
      addition to patient awareness and education for early symptom identification,
      education is required for general practitioners and physicians/intensivists to
      implement early time dependent STEMI management. Percutaneous Coronary
      Intervention (PCI) is the gold standard, yet it remains inaccessible to majority
      of patients, hence early reperfusion by initial use of fibrinolytics is
      recommended followed by coronary intervention. Fibrinolytics are easily
      available, economical and evaluated in several clinical studies and hence we
      recommend a PI approach (early fibrinolysis followed by PCI 3-24 hours later). We
      recommend a time guided 'Protocol/Plan of Action' for early fibrinolysis and
      implementing a PI approach at the level of general practitioners, non-PCI
      hospitals/nursing homes with intensive care facility and in PCI capable centers.
      For STEMI patients with symptom duration < 6 hours, we suggest administration of
      fibrinolytics either tenecteplase (Grade1A), reteplase (Grade1B), alteplase
      (Grade1C) or streptokinase (Grade 2B) alongside contemporary adjunctive medical
      therapy for PI approach. The aim of this Consensus Statement is * To provide
      explicit recommendations for practicing clinicians about the early management of
      STEMI and concept of pharmaco-invasive approach * To provide recommendations
      based on the best available evidences, contextualized to the situation in India.
      It must be recognized that even when randomized clinical trials have been
      undertaken, treatment options may be limited by resources. The Cardiocare STEMI
      experts realize that the recommended diagnostic examinations and treatment
      options may not be available or affordable in all parts of India. Cost
      effectiveness is becoming an increasingly important issue when deciding upon
      therapeutic strategies. As always with guidelines/consensus statement, they are
      not prescriptive. Clinical scenario and patients vary so much from one another
      that individual care is paramount, and there is still an important place for
      clinical judgment, experience, and common sense. The mandate of the Cardiocare
      STEMI expert consensus is to recommend evidence-based standards of care, related
      targets and strategies for implementation of standards in the management of
      STEMI. CONTEXT AND USE: This document should be taken as consensus
      recommendations by qualified experts, not as rigid rules. It comprises of
      published evidence and may not cover every eventuality; new evidence is published
      every day. Furthermore, this should not be used as a legal resource, as the
      general nature cannot provide individualized guidance for all patients under all
      clinical circumstances.

PMID- 25856916
TI  - Ice pack test in myasthenia gravis.

PMID- 25856917
TI  - Spontaneous pyopneumopericardium.

PMID- 25856918
TI  - Concomitant culture negative native mitral and tricuspid valve endocarditis.

PMID- 25856919
TI  - Disseminated cysticercosis in an immunocompetent host--an uncommon presentation.

PMID- 25856920
TI  - Recurrent intestinal obstruction with acquired angio-oedema, due to C1-esterase
      inhibitor deficiency.
AB  - A 52-year male with past history of ulcerative colitis 20 years back (now in
      remission), developed recurrent small intestinal obstruction at intervals of a
      few months. CT scan did not detect the cause initially. A repeat CT scan (USA)
      showed interbowel fluid with transient ascites (serum albumin normal). Angio
      oedema was suspected and low C4 with C1-esterase inhibitor (C1-INH) deficiency
      confirmed the diagnosis. Further investigation showed he was suffering from a
      chronic low grade small B cell lymphoma. He was treated with Rituximab 375 mg/m2
      at intervals of one week for 4 weeks. He is asymptomatic with Transexamic acid
      (500 mg TDS) for last 11/2 years.

PMID- 25856921
TI  - Dieulafoy disease of stomach--an uncommon cause of gastrointestinal system
      bleeding.
AB  - Dieulafoy disease is an uncommon cause of gastrointestinal system bleeding. It is
      characterised by bleeding from abnormal submucosal arteriole. Endoscopic therapy
      and surgery are the preferred treatment option for this lesion. Paul Georges
      Dieulafoy (1839-1911), a professor of pathology in Paris, France, was the first
      to describe a series of 10 patients who presented with Dieulafoy disease. The
      advent of endoscopy has drastically changed the process of diagnosing and
      treating Dieulafoy lesions, with techniques such as endoscopic banding,
      haemoclips, thermocoagulation, and injections with adrenaline as alternatives to
      replace surgical management as was described to be a best practice management.

PMID- 25856922
TI  - Mild mitral and tricuspid regurgitation secondary to pericardial constriction.
AB  - A 26 years female presented with pericardial effusion. On follow up she developed
      pericardial constriction with new appearance of mild mitral and tricuspid
      regurgitation without any other pathology. Fibrosis along posterior
      atrioventricular groove could be responsible for regurgitation.

PMID- 25856923
TI  - Hepatolenticular degeneration--is the term too narrow to explain Wilson's
      disease?
AB  - Wilson's disease is known for its protean manifestations due to abnormal copper
      metabolism. Although liver, brain and eyes are the well established sites for the
      latter but it can be speculated for other organs too. We report a case of
      Wilson's disease with tricuspid regurgitation possibly due to abnormal deposition
      of copper in heart.

PMID- 25856924
TI  - Cytomegalovirus reactivation in drug induced hypersensitivity syndrome.
AB  - Drug induced hypersensitivity syndrome has been reported to a variety of drugs.
      Reactivation of herpes viruses is associated with relapse of symptoms even as
      late as five weeks after stopping the inciting drug. We report here a case of
      drug hypersensitivity with CMV reactivation which was treated successfully.

PMID- 25856925
TI  - Hyperventilation of pregnancy presenting with flaccid quadriparesis due to
      hypokalaemia secondary to respiratory alkalosis.
AB  - Hyperventilation in pregnancy is a cause of chronic respiratory alkalosis.
      Alkalosis either metabolic or respiratory may cause intracellular shift of
      potassium ions that may lead to hypokalaemia. However, the resultant hypokalaemia
      in respiratory alkalosis is usually mild and does not cause much clinical
      features. A five-months-pregnant female of the age 25 years presented with sudden
      onset flaccid weakness of both lower limbs associated with thigh muscle pain
      followed by weakness of both upper limbs within three days. Subsequent
      investigation revealed severe hypokalaemia due to acute exacerbation of chronic
      respiratory alkalosis secondary to hyperventilation of pregnancy, other causes of
      hypokalaemia being ruled out. Respiratory alkalosis causes tetany and other
      clinical manifestations. But hypokalaemia and such weakness is rarely found.
      Thisis probably the first report of this type from India.

PMID- 25856926
TI  - Hereditary amyloid polyneuropathy in a family from North West India: phenotypic,
      MRI and pathologic study.
AB  - Hereditary amyloid polyneuropathies are rare, heterogeneous group of autosomal
      dominant disorders and deserve special attention because of its rare
      presentation, multisystem involvement and significant therapeutic implications if
      diagnosed early. We report a male patient of hereditary amyloid polyneuropathy
      from North West India with peripheral nerve, autonomic nervous system, vitreous
      and cardiac involvement.

PMID- 25856927
TI  - Edward Calvin Kendall.

PMID- 25856928
TI  - Diabetic foot and Heberprot-P.

PMID- 25856929
TI  - Leptospirosis: need for diagnostic criteria.

PMID- 25856930
TI  - Mucormycosis in patients without cancer: a case series from a tertiary care
      hospital in South India.

PMID- 25856932
TI  - Intra-articular steroids in 'treat-to-target' therapy in early rheumatoid
      arthritis.

PMID- 25856931
TI  - Reply from author.

PMID- 25856933
TI  - Comparison of intra-articular glucocorticoid injections with DMARDs versus DMARDs
      alone in rheumatoid arthritis.
AB  - BACKGROUND: Intra-articular triamcinolone in combination with DMARDs may be able
      to achieve faster and tighter control of disease activity in early rheumatoid
      arthritis that may be the key to preventing or minimizing later deformities.
      OBJECTIVE: To compare the efficacy of a combination of Disease Modifying Anti
      Rheumatoid Drugs (DMARDs) with Intra-articular Glucocorticoids versus only DMARDs
      in a group of patients with early Rheumatoid Arthritis (RA). METHODS: Fifty
      patients diagnosed as Rheumatoid Arthritis (RA) by American Rheumatology
      Association (ARA) criteria (1987) with disease duration less than two years were
      randomized into two groups. The Control group received a combination of
      Methotrexate 15 mg daily with Sulfasalazine 2 gm daily for 3 months and the Study
      group received the above combination along with Intra-articular injections of
      Triamcinolone acetate (40 mg per ml) in each of the swollen joints at the start
      of the study. Outcome was assessed in terms of Disease Activity Score (DAS-28),
      American College of Rheumatology (ACR) 20/50/70 criteria and number of rescue
      medications used at the end of 3 months. RESULTS: The study group had significant
      reductions in DAS 28 scores (3.39 versus 4.99 in control group) and significantly
      more subjects achieved the ACR 20/50/70 criteria at the end of 3 months
      (100/60/36% versus 84/20/0%) Secondary end-points like tender and swollen joint
      count, ESR, early morning stiffness, health assessment questionnaire (HAQ) scores
      and general health status were significantly reduced in the study group. Also,
      significantly lesser rescue medications were needed in the study group.
      CONCLUSION: Combination of DMARDs with Intra-articular corticosteroids is
      significantly better than DMARDs alone in early RA.

PMID- 25856934
TI  - Estimation of vitamin D levels in rheumatoid arthritis patients and its
      correlation with the disease activity.
AB  - AIM: To detect level of serum vitamin D in patients of Rheumatoid arthritis (RA)
      and to establish relationship between serum vitamin D level and disease activity
      in RA. METHOD: Eighty patients of RA fulfilling 1987 revised criteria of the
      American College of Rheumatology (ACR) of RA classification and eighty healthy
      controls were included in the study. 25 (OH) vitamin D levels were measured.
      Disease activity was assessed by DAS-28 score. RESULTS: Ninety percent of RA
      patients were either vitamin D deficient or insufficient while only seventy
      percent of healthy controls were either vitamin D deficient or
      insufficient(p=0.007). Mean serum vitamin D levels of RA patients was
      significantly low compared to healthy controls (p=0.009). Thirty-one patients had
      high disease activity (DAS-28 score >5.1, group A), 32 patients had moderate
      disease activity (DAS 28 score 3.2-5.1, group B) and 17 patients had low disease
      activity (DAS-28 score <3.2, group C). Vitamin D levels in high disease activity
      group was significantly low compared to vitamin D level in patients with low and
      moderate disease activity (p<.001) and vitamin D level had significant negative
      correlation with DAS28 score (r=-0.604, p<0.001). CONCLUSION: Serum vitamin D
      levels were significantly low in RA patients than in healthy controls. Vitamin D
      deficiency was seen in significantly higher numbers of patients and vitamin D had
      negative correlation with disease activity in RA.

PMID- 25856935
TI  - A study of newly diagnosed type 2 diabetes mellitus patients from rural areas.
AB  - OBJECTIVE: To study the clinical and biochemical profile of newly diagnosed type
      2 diabetes mellitus patients who belong to rural areas. METHODOLOGY: The study
      was conducted on 105 newly diagnosed type 2 diabetes mellitus patients. A
      detailed history and thorough clinical examination was done. Anthropometric
      measurements were recorded. Investigations were done to assess micro vascular,
      macro vascular complications and lipid profile. RESULTS: There were 54 males and
      51 females. The mean age of patients was 49 years. The mean BMI of males was 23.3
      kg/m2 while that of females was 25.9 kg/m2. Waist Hip ratio was 0.97 in males and
      0.92 in females. 30% patients had hypertension. 30% patients had a serum
      triglyceride level more than 150 mg%, 20% patients had total serum cholesterol
      more than 200 mg%, 10% patients had LDL cholesterol more than 130 mg%. The
      prevalence of neuropathy, retinopathy and nephropathy was 23%, 15% and 19%
      respectively. CONCLUSION: The present study shows that newly diagnosed type 2
      diabetic rural males have a near normal BMI even by the Indian criteria. The
      waist circumference of males was also within normal limits for Indians.
      Prevalence of metabolic syndrome was also very low in newly diagnosed male
      patients.

PMID- 25856936
TI  - Diagnostic utility of serum GH, IGF-1 and IGFBP3 in patients of acromegaly with
      uncontrolled diabetes: a pilot study.
AB  - PURPOSE: Diagnosis of acromegaly in presence of uncontrolled diabetes mellitus is
      not well validated. METHOD: The study included 10 patients of active acromegaly
      with uncontrolled blood glucose, 10 patients of type 2 diabetes mellitus with
      poor glycemic control and 10 healthy subjects. The growth hormone level following
      oral glucose tolerance test and insulin-like growth factor-1 (IGF-1) and insulin
      like growth factor-binding protein-3 (IGFBP-3) were done at baseline in all the 3
      groups and it was repeated after short term glycemic control in type 2 diabetics
      and acromegalics with diabetics RESULTS: In the acromegalic group the basal GH
      value was very high (36.5 + 1.6) ng/ml and it was non-suppressible (32.5 + 1.43)
      ng/ml after OGTT. The mean IGF-1 and IGFBP-3 values were also high at baseline
      (208.38 + 38.51) ng/ml, and 7322 + 370 ng/ml respectively. In the non-acromegalic
      diabetic patients, the basal growth hormone value was marginally elevated (2.3 +
      0.02) ng/ml. However, it was suppressible to 0.2 + 0.04 ng/ml after oral glucose
      load. In them the IGF-1 and IGFBP-3 values were not elevated and comparable to
      that of healthy controls. CONCLUSIONS: Basal serum GH and IGFBP-3 levels are not
      influenced by degree of glycemic control however serum IGF-1 levels should be
      interpreted with caution in patients of acromegaly with diabetes. Oral glucose
      load test has discriminating ability to diagnose acromegaly even with poorly
      controlled diabetes.

PMID- 25856937
TI  - Clinico-pathological corelation: a search for the cause of myelofibrosis.

PMID- 25856938
TI  - Hepatorenal syndrome: a decade later.
AB  - Hepatorenal syndrome is a unique form of acute kidney injury seen in patients
      with acute liver failure or chronic liver disease in absence of any other
      identifiable cause of renal failure. It is primarily a diagnosis of exclusion.
      Despite of good pathophysiological understanding and better available therapeutic
      options for management of hepatorenal syndrome, it is still associated with
      significant morbidity and mortality. Liver transplantation forms the cornerstone
      for its management. In this review article, we have attempted to assimilate and
      summarise the advances made in the previous decade with regards to
      pathophysiology, classification and management of this entity.

PMID- 25856939
TI  - Mucosal bridge in oesophagus.

PMID- 25856940
TI  - 'Double-arch' sign and 'air-bubble' sign--two radiological signs of ruptured
      hydatid cyst in lung.

PMID- 25856941
TI  - Dracunculosis--a disease of yesteryears.

PMID- 25856942
TI  - Face of giant panda sign in Wilson's disease.

PMID- 25856943
TI  - Hypermobility syndrome.
AB  - Three cases of Hypermobility Syndrome (HS) are discussed. The first case was a
      young female, aged 24, with musculoskeletal symptoms since 5 years. Second was an
      18 year old male with similar symptoms since 3 years. The third was an elderly
      female who presented with knee joint osteoarthritis (OA) and apparent but
      reducible deformities of hands mimicking rheumatoid arthritis (RA). All three
      patients had hypermobility of joints in absence of demonstrable systemic
      rheumatic disease. The prevalence, clinical features and management of the entity
      is discussed. An increased awareness of this condition among physicians is
      warranted as some patients may be erroneously diagnosed as RA/SLE and may be put
      on DMARDs and steroids.

PMID- 25856944
TI  - Generalised hyperpigmentation in vitamin B12 deficiency.
AB  - In developing countries like India, nutritional deficiencies are prevalent and
      hyperpigmentation due to protein energy malnutrition, zinc deficiency and
      pellagra are common. Indian women, especially vegetarian are prone to vitamin B12
      deficiency. Vitamin B12 deficiency can present as anaemia, neurological defect,
      gastrointestinal symptoms or dementia. Hyperpigmentation as the first
      presentation of Vitamin B12 deficiency is rare. Our patient, a 45 year-old Hindu
      vegetarian female presented to us with generalized hyperpigmentation. Examination
      revealed associated anaemia and peripheral neuropathy. Laboratory investigation
      confirmed vitamin B12 deficiency. Clinical features along with hyperpigmentation
      improved with vitamin B12 supplementation. We report this case to highlight this
      rare manifestation of vitamin B12 deficiency. A high index of clinical suspicion
      is warranted to diagnose the case. Since India is a country with a large number
      of potential vitamin B12 deficiency cases, the physicians need to be aware of all
      the varied manifestations of this vitamin deficiency. In case of
      hyperpigmentation, nutritional aspect must be ruled out as it is reversible.
      Early replacement therapy may also help to prevent morbidities like dementia and
      neuropathy.

PMID- 25856945
TI  - Acquired perforating dermatosis in a patient of diabetes mellitus with chronic
      kidney disease.
AB  - Acquired perforating dermatosis characterised by the transdermal excursion of
      dermal material which clinically presents as umbilicated skin-coloured papules
      with a central white crust. A 45 year old male patient with diabetic nephropathy
      presented with similar lesion and itching. Diagnosis was confirmed by biopsy from
      appropriate site. Patient responded well to emollients, low dose-retinoids, broad
      spectrum renal friendly antibiotics and haemodialysis.

PMID- 25856946
TI  - HIV associated Burkitt's lymphoma.
AB  - Burkitt's lymphoma (BL) is a highly aggressive B-cell non-Hodgkin Lymphoma (NHL)
      associated with chromosomal translocations resulting in upregulation of the proto
      oncogene C-MYC, which drives progression through the cell cycle NHL accounts for
      approximately one third of AIDS-related malignancies and the frequency of BL is
      2.4-20% of HIV-associated NHL. The outcome of HIV-associated non-Hodgkin lymphoma
      (NHL) has improved substantially in the highly active antiretroviral therapy
      (HAART) era. However, HIV-Burkitt lymphoma (BL), which accounts for up to 20% of
      HIV-NHL, still has poor outcome with standard chemotherapy. We present here a 26
      years old female who presented with congestive cardiac failure and sudden onset
      paraparesis and was finally diagnosed to have right atrial mass and had
      extradural lesion extending from L2 to S1 which turned out to be High grade NHL
      Burkitt's Lymphoma.

PMID- 25856947
TI  - Dapsone hypersensitivity syndrome with myocarditis.
AB  - Drug hypersensitivity with myocarditis is known to occur with many drugs
      especially with antiepileptics, sulpha-compounds and daposne. Dapsone (4, 4
      diaminodiphenyl sulphone) induced hypersensitivity is known to occur in about 2%
      of leprosy patients on treatment and an incidence of 1.66% in non-leprosy
      patients. We report this rare case of dapsone hypersensitivity syndrome in a girl
      on dapsone who presented with fever, anaemia, jaundice, skin rash,
      lymphadenopathy, and hepatomegaly and later developed myocarditis. The drug was
      withdrawn and the patient was treated with steroids. She improved and was
      discharged. She relapsed after the corticosteroids were discontinued at home.

PMID- 25856948
TI  - A case of cerebellar dysarthria as the presenting symptom of HIV infection.
AB  - A 37 year old man presented with progressive dysarthria for 2 weeks. A week later
      he developed ataxia and bilateral cerebellar signs including intention tremors,
      dysmetria and dysdiadokokinesia. During evaluation for aetiology of cerebellar
      dysarthria, MRI brain revealed asymmetric altered signal intensities in bilateral
      cerebellar hemispheres and right side of pons suggesting demyelinating lesions.
      ELISA for Human Immune Deficiency virus-1 was positive. We kept a presumptive
      diagnosis of Progressive Multifocal Leukoencephalopathy (PML) on the basis of
      clinico-radiological picture. PML is an under investigated and under diagnosed
      CNS infection seen in HIV patients with advanced disease. We present an unusual
      case report where isolated cerebellar involvement occurred as the first AIDS
      defining event in the absence of appreciable immunodeficiency in a patient with
      previously undiagnosed HIV infection.

PMID- 25856949
TI  - Reversible cardiomyopathy in Guillain Barre syndrome.
AB  - The clinical manifestations of Guillain Barre syndrome are usually confined to
      the nervous system, however in 20% cases there can be cardiovascular involvement
      in patients with dysautonomia contributing to the mortality. The cardiovascular
      manifestations of Guillain Barre syndrome are electrocardiographic changes,
      cardiac enzyme abnormalities and reversible left ventricular dysfunction. The
      term neurogenic stunned myocardium has been used to summarise these
      cardiovascular abnormalities in the setting of severe central nervous system
      injury, in the absence of coronary artery disease. Our case report of reversible
      cardiomyopathy in Guillain Barre syndrome documents the occurrence of
      cardiovascular changes in a case of Guillain Barre syndrome with dysautonomia
      which were reversible with appropriate treatment.

PMID- 25856950
TI  - Methaemoglobinaemia as a result of nitrite poisoning.
AB  - Methaemoglobinaemia due to nitrite poisoning is rare. Awareness of this condition
      in the cyanosed patient not responding to oxygenation and timely administration
      of methylene blue may be life saving. We report a case of methaemoglobinaemia as
      a result of sodium nitrite poisoning.

PMID- 25856951
TI  - Myocardial infarction following bee sting.
AB  - Bee stings are commonly encountered worldwide. Various manifestations after bee
      sting have been described. Local reactions are common. Unusually, manifestations
      like vomiting, diarrhoea, dyspnoea, generalised oedema, acute renal failure,
      hypotension and collapse may occur. Rarely vasculitis, serum sickness, neuritis
      and encephalitis have been described which generally develop days to weeks after
      a sting. Acute coronary syndromes after hymenoptera stings and other
      environmental exposures are referred to as the Kounis syndrome or allergic
      myocardial ischaemia and infarction. We report a 60 year old male who developed
      myocardial infarction after multiple bee stings over his body.

PMID- 25856952
TI  - Acute venous sinus thrombosis after chickenpox infection.
AB  - BACKGROUND: Chickenpox is one of the classic childhood diseases. Recently chicken
      pox has been reported in adults with more severe systemic and neurological
      complications. Cerebral venous thrombosis (CVT) is a life threatening disorder if
      not treated in time. We report a patient with post varicella CVT as a rare
      complication of primary Varicella zoster virus. CASE REPORT: Vasculitic arterial
      infarction is known while venous stroke has rarely been reported with Varicella
      zoster virus infection. Here, we report an immunocompetent 30 yr old male who
      developed chickenpox after contact with his daughter two month back. He presented
      with acute neurological deficit, one week after onset of skin lesion. MR
      venography revealed non-visualisation of left transverse sinus and left sigmoid
      sinus suggestive of venous sinus thrombosis. CONCLUSION: Varicella infection is
      rarely associated with venous sinus thrombosis. Possibly hypercoagulable state
      produced by the infection or direct invasion of virus in venous endothelial wall
      with subsequent damage to endothelium leading to thrombosis could be the cause.

PMID- 25856953
TI  - Unusual presentation post renal transplant lymphocele.
AB  - Retroperitoneal lymphocele is one of the common complications following renal
      transplantation, and usually present with persistent lymphatic drain in immediate
      post transplant period or perigraft collection in post transplant routine
      ultrasound. In this case report, we present a renal transplant recipient who
      presented with acute urinary retention and right sided lower limb swelling
      mimicking deep vein thrombosis (DVT), due to a large lymphocele behind the
      bladder compressing bladder neck and common iliac vessels, approximately 2 months
      after renal transplant. Though lymphocele is not uncommon post transplant
      complication, the presentation of lymphocele after 2 months post transplant with
      pressure effect of this type is uncommon. In this case, pressure on common iliac
      vessels mimicking DVT and on bladder neck, leading to acute retention of urine
      and leading to hydronephrotic graft; which occurred in CNI (Cyclosporine) based
      regimen is extremely rare.

PMID- 25856954
TI  - Leprous polyneuritis cranialis mimicking orbital apex syndrome.
AB  - Leprosy is one of the most prevalent infections in India, with our country
      accounting for almost 60 percent of the world's patients. Hence unusual
      presentations of leprosy should be sought for and treated at the earliest. We
      report this rare case of polyneuritis cranialis secondary to leprosy. Affection
      ofa single cranial nerve has been described previously but there is only one
      report of leprosy presenting like orbital apex syndrome.

PMID- 25856955
TI  - Familial juvenile hyperuricemic nephropathy 1 (FJHN1).
AB  - Familial juvenile hyperuricemic nephropathy 1 (FJHN1) is an autosomal dominant
      disorder characterized by decreased urinary excretion of urate and hyperuricemia,
      followed by the development of chronic interstitial nephritis most often leading
      to progressive renal failure and death in middle age. We report a case of FJHN1
      presenting as chronic tophaceous gout, hypertension, renal failure and a family
      history suggestive of autosomal dominant inheritance, for its rarity.

PMID- 25856956
TI  - A case of primary amenorrhoea.
AB  - OBJECTIVE: To report a case of primary amenorrhoea and to describe an approach to
      evaluation. METHODS: Primary amenorrhoea can be due to diverse causes and needs
      detailed and astute evaluation. We report the case of a 17 years old individual
      born and brought up as a female, who was brought to us with primary amenorrhoea.
      Approach to such a patient with a review of available published literature is
      described. RESULTS: After detailed history, biochemical testing, imaging and
      karyotyping, we found that this patient had a XY karyotype with normal uterus,
      fallopian tubes and vagina, but streak gonads. CONCLUSION: Swyer syndrome (46,XY
      gonadal dysgenesis), a sex reversal disorder characterized by a phenotypic female
      with non-functional streak gonads, poorly developed secondary sexual characters,
      primary amenorrhoea and 46,XY karyotype was diagnosed. This patient was treated
      with gonadectomy and sex hormone replacement.

PMID- 25856957
TI  - Methyl alcohol poisoning: a manifestation of typical toxicity and outcome.
AB  - Methyl alcohol poisoning is an uncommon but an extremely hazardous poisoning. It
      most commonly occurs via oral ingestion of illicit or adulterated liquors or as
      ethanol substitution. The clinical diagnosis is made in the presence of high
      index of suspicion of toxic alcohol ingestion, early visual symptoms, unexplained
      anion gap metabolic acidosis and significant osmolar gap. Rapid recognisation,
      early and aggressive management have been emphasized to prevent hazardous
      outcome. We report a case of methyl alcohol poisoning manifestation of typical
      toxicity and outcome which revealed severe metabolic acidosis with high anion
      gap, blindness complicating bilateral optic atrophy and putaminal hemorrhagic
      necrosis. The patient improved with aggressive treatment including oral ethyl
      alcohol, but the occurrence of permanent blindness could not be prevented
      probably due to late presentation.

PMID- 25856958
TI  - Sir John Charnley.

PMID- 25856959
TI  - Josef Dietl (1804-1878)--medical reformer and "his crisis".

PMID- 25856960
TI  - Comparing conventional and analogue insulin in hospitalised patients.

PMID- 25856961
TI  - National Epilepsy Programme.

PMID- 25856962
TI  - Reply from author.

PMID- 25856963
TI  - Pharmacokinetics of a single dose (15 mg) primaquine in chronic kidney disease
      patients undergoing haemodialysis.

PMID- 25856964
TI  - [Editorial].

PMID- 25856965
TI  - [Infantile hemangioma: a new indication for propranolol? Retrospective study: a
      case-series of 25 infants].
AB  - BACKGROUND: In 2008, the New England Journal of Medicine reported a new
      indication for propranolol: treatment of complicated infantile hemangioma (IH).
      The objective of this study is to identify any adverse events and to measure the
      efficacy of propranolol in children with complicated IH, through a retrospective,
      observational, case-series study of 25 patients treated with propranolol at the
      Hopital Universitaire des Enfants Reine Fabiola in Belgium. OBSERVATIONS: 25
      patients were submitted to this therapy. The treatment was stopped prematurely
      for two of them, by parental fear of side effects and 48 % presented one or more
      adverse events; all of which were transient and rapidly controlled by adjusting
      the doses administered. Mean age at the start of treatment was 4,8 months. A
      clearly favorable response was observed in 100 % of patients at their first visit
      after treatment initiation ; a total response was seen in 9 patients, with
      subtotal and partial responses observed in 9 and 3 patients, respectively, by the
      end of treatment. CONCLUSION: The real efficacy of propranolol for complicated IH
      was confirmed by the clearly evident improvement observed in all patients and the
      absence of non-responders. As global tolerance was also good, propranolol can
      therefore be considered to be an appropriate first- line treatment for
      complicated IH.

PMID- 25856966
TI  - [Evaluation of microalbuminuria and lipid profile among type 2 diabetics].
AB  - OBJECTIVE: To establish the respective prevalence of microalbuminuria and
      dyslipidemia and to evaluate their association with diabetes type 2. ANALYZE
      DATA: Prospective study of 195 type 2 diabetic subjects (125 women and 70 men)
      from a hospital in the city of Dakar (Senegal) for a check-up of diabetes. Age
      and sex were determined ; fasting blood glucose, glycated hemoglobin, total
      cholesterol, HDL cholesterol, LDL cholesterol, triglycerides and micro-
      albuminuria were measured. RESULTS: In this study, the mean age of patients was
      57.9 +/- 11.1 years. Age, glycated hemoglobin and microalbuminuria were
      significantly higher in women than in men (P < 0.01 ; P < 0.03 ; P < 0.01
      respectively). The prevalence of microalbuminuria is 48.7% and that of
      dyslipidemia is 41.1%. Glycated hemoglobin is higher in subjects with
      microalbuminuria than in patients with normal microalbuminuria with a
      statistically significant difference (P < 0.001). There is a strong correlation
      (R = 0.82) between glycated hemoglobin and microalbuminuria, 1% increase in HbA1c
      corresponding approximately to an increase of 39.7 mg/I of microalbuminuria.
      CONCLUSION: Microalbuminuria and dyslipidemia are frequently found in type 2
      diabetes, but the pathophysiological mechanisms of the association are not well
      known.

PMID- 25856967
TI  - [One year functioning of a psychiatric unit in a general hospital: analyses and
      reflections].
AB  - At a time where the organization of mental health care in Belgium is profoundly
      modified by the development of an ambulatory option, following as such the
      proposals of the WHO, it seemed interesting to measure the present functioning of
      a psychiatry unit located in a general hospital. Data concerning the psychiatry
      unit of C.H.U. Tivoli, at La Louviere, were analyzed over a period of one year.
      The age pyramid followed a Gaussian curve, with a peak at age 45, a period of
      life considered as one of the most difficult in surveys over general life
      satisfaction. The main reasons for admission were: major depressive disorder,
      alcohol desintoxication, looked for isolation from the external world (either for
      physical or psychological reasons), diagnostic (morbidities and comorbidities)
      and therapeutic (complex treatment combinations) workups, anxious and psychotic
      decompensations, and systemic conflits (e.g. conflicts within the family). The
      number and duration of admissions showed peaks in september-october, january
      february and june-july. The most current stay duration was 6 days. A subgroup
      completed an additional survey about the ideal localization for their care. 19 %
      would have opted for an ambulatory care if the choice would have been proposed.
      By contrast, it appears that hospitals, with their concentration of disciplines
      in the same location and relatively efficient organization, still has an
      important role to play in the future network in mental health care.

PMID- 25856968
TI  - [Psoriasis and depression].
AB  - Psoriasis is a common inflammatory disease affecting 2%-5% of the population of
      industrialized countries. Although the association between psychiatric
      pathologies and dermato- logical conditions is well known, the dermato- logist
      fails to indentify the psychological distress and when he identifies it, he
      doesn't take care of this suffering. The biological links between psoriasis and
      depression are now well-established. The impact on the quality of life (QoL) is
      studied for several years. In this vast domain of the QoL, the first problem
      revealed by the patients is the feeling of stigmatization. In psoriasis, the
      psychiatric comorbidity is estimated approximately at 30 %. The psychiatric
      troubles the most associated with dermatological conditions in general are
      depression, anxiety and suicidal ideations. The prevalence of depression in
      patients with psoriasis is estimated between 10 % and 62 % according to different
      studies. The patient's psychological distress is not correlated to the intensity
      of the clinical symptoms and the treatment does not modify either this distress,
      the coping mechanism, or the patient's opinion about his skin condition.
      Furthermore, it is necessary to know that the dermatological diseases affecting
      the patients during their childhood or adolescence will have a significant effect
      on the formation of their personality. However, personality will have an
      influence on the psychological morbidity. Therefore, it is important to take care
      of young people. To help the physician to recognize these difficulties, we
      propose a review of the literature and a method for a better management of the
      psychological suffering often experienced by the patients with psoriasis.

PMID- 25856969
TI  - [Botulinum toxin injection for refractory non-neurogenic overactive bladder.
      Systematic review].
AB  - BACKGROUND: OAB is common with a potential negative impact on quality of life.
      Anticholinergics and beta3-mimetics are the first-line medical treatment. This
      treatment meets only 50% of patients given a lack of efficacy and adverse
      effects. Used in the treatment of neurogenic overactive bladder, botulinum toxin
      is now evaluated for the treatment of refractory non-neurogenic overactive
      bladder. The objective of this work is to review the literature data concerning
      the efficacy and safety of intradetrusor botulinum toxin injections to treat
      refractory idiopathic overactive bladder. METHODOLOGY: A systematic literature
      review was conducted to identify articles published between May 1988 and April
      2013 in Medline for the treatment of refractory idiopathic overactive bladder
      with botulinum toxin. RESULTS: 37 studies with original samples were selected
      including 8 randomized controlled trials against placebo. The effectiveness of
      intra- detrusor injections is demonstrated to reduce the frequency, urgency,
      nighttime urination, incontinence episodes and to improve bladder capacity and
      quality of life. The most common side effects are incomplete bladder emptying,
      intermittent catheterization and increased risk of urinary tract infection. A
      dose of 100 to 150 U of onabotulinumtoxinA allows the best compromise between
      efficiency and tolerance. Duration of the effects varies between 3 to 12 months
      and repeating the injections did not seem to affect the efficiency. Injections
      including the trigone zone do not cause vesicoureteral reflux. The absence of
      detrusor hyperactivity does not alter the clinical response. CONCLUSION: The
      detrusor injections of botulinum toxin can be considered as an effective second
      line treatment for refractory non-neurogenic overactive bladder. Information on
      intermittent catheterization risk must be provided. The very long-term
      effectiveness and the absence of urothelium alterations are still outstanding
      issues.

PMID- 25856970
TI  - [Mono-arthritis of the hand: case report of osteoid osteoma].
AB  - Osteoid osteoma is a rare occurrence at the hand. There is often a long delay
      before the diagnosis because the clinical signs mimic other frequent affections
      of the hand. We report the case of a 24-year old female patient suffering from an
      osteoid osteoma in the first phalanx of a finger. The diagnosis was made four
      years after the first symptoms. We started by a curettage-biopsy, followed in a
      second operative step by cauterization and filling up the defect by a bone
      autograft. Six months after the surgery, the patient was no longer experiencing
      any symptom. This rare case demonstrates that osteoid osteoma remains a possible
      diagnosis in chronic pain affecting the hand.

PMID- 25856971
TI  - [An unusual digestive occlusion].
AB  - Malignant melanoma is a rapidly metastatic disease. Metastasis in the small
      intestine is as such not uncommon, whereas the clinical presentation of
      obstruction due to intussusception is very rare. We hereafter report the case of
      a 58-year-old female admitted with general degradation, syndrome of intestinal
      occlusion and a cervical mass. Imaging studies showed signs suggesting an
      invagination of the small intestine. A resection of the cervical mass and
      segmental small intestine resection were performed. Pathological findings
      revealed a cervical malignant melanoma spread into the small intestine. The
      diagnosis of intestinal metastasis should therefore be considered in patients
      with intestinal occlusion and history of melanoma and presenting gastrointestinal
      symptoms.

PMID- 25856972
TI  - [Control of the legal practice of euthanasia in Belgium].
AB  - The Belgian law legalizing euthanasia under strict conditions came into effect
      September 22, 2002. Any physician performing euthanasia has to complete a
      registration document and to send it within four days to a federal commission
      whose mission is to verify that the legal conditions were fulfilled. From
      September 22, 2002 to December 31, 2013, 8.767 documents have been registered and
      analyzed by this commission. They are described in six reports referred to
      Parliament. The present paper analyzes the work of this commission and answers
      the criticisms concerning its quality and its efficiency. The allegations that
      clandestine euthanasia's escaping any control are performed are also discussed.
      In conclusion, it appears that the legal obligations concerning the practice of
      euthanasia in Belgium are fully effective.

PMID- 25856973
TI  - [Relations between the scientific thought and the medicine: the contributions of
      Plato and Aristotle].
AB  - Since the advent of philosophy and rational thought, a question has been raised:
      Is medicine an art, a science, a technique, or the three of them? In this paper
      we discuss two monuments of Western thought that have approached this topic:
      Plato and Aristotle. For Plato, medicine is focused on what is transient and
      changing and therefore it is a subordinate science. However, he has a positive
      view because it presupposes knowledge of all and he takes medicine as a
      dialectical model. Aristotle places medicine in his classification of sciences.
      He emphasizes the idea that the purpose of medicine is based on what "happens
      most often" and insists on essential role of experimentation. It is remarkable to
      notice that these ideas developed 2.500 years ago are still relevant and remain
      the core of the epistemological conceptions of modern medicine.

PMID- 25856974
TI  - [In honor of Professor Philippe Martiat].

PMID- 25856975
TI  - [Clinical analysis of nontuberculous mycobacterial infection complicated by
      pleurisy].
AB  - OBJECTIVE: There are few reports describing pleurisy caused by nontuberculous
      pulmonary mycobacteriosis; in addition, there are few reports describing the
      frequency of cases. METHOD: We retrospectively studied 116 consecutive cases of
      nontuberculous mycobacteriosis occurring between January 2009 and January 2014.
      RESULT: Of these, 7 patients (6.0%) were diagnosed with pleuritis caused by
      nontuberculous pulmonary mycobacteriosis. One patient each had a history of
      ulcerative colitis, rheumatoid arthritis treated with steroids, and retinitis
      pigmentosa. Pleural effusion was examined in all 7 cases. In addition,
      nontuberculous mycobacteria were cultured from pleural effusion in 4 of the 7
      cases; all were cases of Mycobacterium avium complex infection. The mean
      adenosine deaminase level in pleural effusion was 86 U/mL, and in 5 out of 7
      cases, the adenosine deaminase level was greater than 50 U/mL. Pneumothorax
      occurred with pleuritis in 5 cases. Pleuritis was treated with NTM therapy in 5
      cases, and pleural effusion decreased or cleared completely in all cases.
      CONCLUSION: To reveal pleurisy accompanied by nontuberculous mycobacteriosis,
      further consideration is needed.

PMID- 25856976
TI  - [Tuberculosis annual report 2012--(4) Tuberculosis treatment and outcomes].
AB  - Re-treatment frequency among patients newly diagnosed with tuberculosis (TB)
      might indicate inadequate prior treatment. Of 21,283 patients diagnosed with TB
      in 2012, 1,336 had received prior TB treatment. Among patients requiring re
      treatment, more than half (n = 749) had received treatment after 2000. The
      initial recommended TB treatment regimen in Japan consisted of a combination of
      isoniazid, rifampicin, pyrazinamide, and ethambutol or streptomycin. This regimen
      was used to treat approximately 90% of patients aged 15-49 years with all forms
      of TB. However, the proportion of patients substantially declined among patients
      >= 80 years of age. Of 13,650 patients who started a pyrazinamide TB treatment
      regimen in 2011, approximately 10% were unable to complete the 2-month-long
      pyrazinamide regimen by the end of 2012. In 2012, 16,432 patients were newly
      diagnosed with pulmonary TB (PTB). The proportion of patients hospitalized at the
      beginning of TB treatment increased among those >= 30 years of age. The median
      hospitalization duration among newly diagnosed patients with all forms of TB in
      2011 was 64 days. The durations for those who had a new positive sputum smear
      result, were undergoing re-treatment, had a positive sputum result in other
      bacteriological tests, and had bacteriologically negative sputum PTB were 70, 72,
      44, and 39 days, respectively. The median hospitalization duration was 43 days
      among patients with extrapulmonary TB. At the end of 2012, the median treatment
      duration in patients diagnosed in 2011 with all forms of TB was 273 days. The
      treatment success rates for patients who had a new positive sputum smear result
      (n = 7,736), were undergoing re-treatment (n = 747), had a positive sputum result
      in other bacteriological tests (n = 6,049), and had a bacteriologically negative
      sputum result (including other PTB patients) (n = 2,917) registered in 2011 were
      50.6%, 41.2%, 58.0%, and 62.5%, respectively. The rate of loss to follow-up among
      patients who had a new positive sputum smear result and were undergoing re
      treatment was 3.3% each, well below 5%. The mortality rate among patients with
      new sputum smears posi- tive for PTB was 21.6%; > 20% died before completing the
      treatment course. Patients 70-79, 80-89, and >= 90 years of age had relatively
      high death rates (23.9%, 36.6%, and 44.0%, respectively) compared with the other
      age groups.

PMID- 25856977
TI  - [Molecular genetics of pancreatic ductal adenocarcinoma].

PMID- 25856978
TI  - [The molecular mechanism of the invasion and metastasis in the pancreatic ductal
      adenocarcinoma].

PMID- 25856979
TI  - [Pathology of the pancreatic cancer].

PMID- 25856980
TI  - [Desmoplastic reaction in pancreatic cancer].

PMID- 25856981
TI  - [Animal model of pancreatic cancer].

PMID- 25856982
TI  - [Descriptive epidemiology of pancreatic cancer in Japan].

PMID- 25856983
TI  - [Pathological classification of tumors of the pancreas].

PMID- 25856984
TI  - [Tumor marker of pancreatic tumor].

PMID- 25856985
TI  - [US].

PMID- 25856986
TI  - [CT and MR imaging of pancreatic cancer].

PMID- 25856987
TI  - [ERCP].

PMID- 25856988
TI  - [EUS diagnosis for pancreatic tumor].

PMID- 25856989
TI  - [PET imaging in the diagnosis of pancreatic cancer].

PMID- 25856990
TI  - [Current topics and over view of pancreatic juice cytology].

PMID- 25856991
TI  - [EUS-guided fine-needle aspiration biopsy (EUS-FNA) for pancreatic tumor].

PMID- 25856992
TI  - [Epidemiology of pancreatic ductal adenocarcinoma].

PMID- 25856993
TI  - [Risk factors for pancreatic cancer].

PMID- 25856994
TI  - [Conventional ductal adenocarcinoma clinicopathological classification and
      feature].

PMID- 25856995
TI  - [Symptoms, clinical findings and laboratory data in the pancreatic ductal
      adenocarcinoma].

PMID- 25856996
TI  - [An algorithm in the investigation and diagnosis of pancreatic cancer].

PMID- 25856997
TI  - [The clinical practice for the diagnosis of pancreatic cancer].

PMID- 25856998
TI  - [Differential diagnosis].

PMID- 25856999
TI  - [Algorithm for treatment of pancreatic cancer].

PMID- 25857000
TI  - [Open surgical resection for pancreatic cancer].

PMID- 25857001
TI  - [Laparoscopic surgery for pancreatic cancer].

PMID- 25857002
TI  - [Radical dissection].

PMID- 25857003
TI  - [Total pancreatectomy].

PMID- 25857004
TI  - [Systemic chemotherapy for unresectable pancreatic cancer].

PMID- 25857005
TI  - [Efficacy of neoadjuvant chemotherapy for pancreatic carcinoma planned
      resection].

PMID- 25857006
TI  - [Preoperative chemoradiation for pancreatic cancer].

PMID- 25857007
TI  - [Radiotherapy for metastatic lesion of pancreatic cancer].

PMID- 25857008
TI  - [Endoscopic stenting for pancreatic carcinoma].

PMID- 25857009
TI  - [Palliative surgical bypass surgery for patients with pancreatic cancers].

PMID- 25857010
TI  - [Current treatment and prognosis of pancreatic cancer in Japan and Western
      countries].

PMID- 25857011
TI  - [Prognostic factors for long-term survival in patients with pancreatic ductal
      adenocarcinoma].

PMID- 25857012
TI  - [The clinico-pathological character of pancreatic adenosquamous carcinoma].

PMID- 25857013
TI  - [Mucinous carcinoma of the pancreas].

PMID- 25857014
TI  - [Anaplastic carcinoma of the pancreas].

PMID- 25857015
TI  - [Acinar cell carcinoma].

PMID- 25857016
TI  - [Epidemiology of intraductal papillary mucinous neoplasm of the pancreas].

PMID- 25857017
TI  - [Risk factors for malignant and recurrent IPMNs].

PMID- 25857018
TI  - [Clinicopathlogical classifications and their relevance].

PMID- 25857019
TI  - [Intraductal papillary mucinous neoplasm of the pancreas: its mucin profile
      expression].

PMID- 25857020
TI  - [Intraductal papillary mucinousu neoplasm of the pancreas: IPMN--symptom x blood
      examination].

PMID- 25857021
TI  - [Diagnosis of malignant IPMN and tumor extension].

PMID- 25857022
TI  - [Pancreatic ductal carcinoma derived from IPMN and concomitant with IPMN].

PMID- 25857023
TI  - [Differential diagnosis].

PMID- 25857024
TI  - [Indications for resection].

PMID- 25857025
TI  - [Standard operation for intraductal papillary mucinous neoplasm].

PMID- 25857026
TI  - [Limited resection for the cystic tumor of the pancreas].

PMID- 25857027
TI  - [Postoperative surveillance after resection of IPMN].

PMID- 25857028
TI  - [Prognosis of IPMN].

PMID- 25857029
TI  - [Epidemiology of mucinous cystic neoplasm (MCN)].

PMID- 25857030
TI  - [Developmental mechanism of mucinous cystic neoplasm].

PMID- 25857031
TI  - [Clinico-pathological findings of mucinous cystic neoplasm (MCN)].

PMID- 25857032
TI  - [Symptoms and clinical features of MCN].

PMID- 25857033
TI  - [Diagnosis].

PMID- 25857034
TI  - [Differential diagnosis of mucinous cystic neoplasm of the pancreas].

PMID- 25857035
TI  - [Surgical treatment for MCN].

PMID- 25857036
TI  - [Prognosis of mucinous cystic neoplasm of the pancreas].

PMID- 25857037
TI  - [Serous cystic neoplasms].

PMID- 25857038
TI  - [Solid-pseudopapillary neoplasm of the pancreas].

PMID- 25857039
TI  - [Other cystic neoplasm of pancreas].

PMID- 25857040
TI  - [Trends of epidemiology of pancreatic endocrine tumors: a nationwide survey
      analysis in Japan].

PMID- 25857041
TI  - [WHO classification of pancreatic neuroendocrine tumor: overview].

PMID- 25857042
TI  - [Molecular mechanisms of development of pNET].

PMID- 25857043
TI  - [Multiple endocrine neoplasia].

PMID- 25857044
TI  - [Insulinoma].

PMID- 25857045
TI  - [Glucagonoma].

PMID- 25857046
TI  - [Gastrinoma].

PMID- 25857048
TI  - [IGF producing pancreatic islet cell tumor].

PMID- 25857047
TI  - [Pancreatic carcinoid tumor(serotonin-producing pancreatic neuroendocrine
      tumor)].

PMID- 25857049
TI  - [Diagnosis of pancreatic neuroendocrine tumor and medical treatment of endocrine
      symptoms].

PMID- 25857050
TI  - [Non-functioning neuroendocrine tumor of the pancreas].

PMID- 25857051
TI  - [Metastatic tumors to the pancreas].

PMID- 25857052
TI  - [Other pancreatic neoplasms (pancreatoblastoma, hepatoid carcinoma and medullary
      carcinoma)].

PMID- 25857053
TI  - [Malignant lymphoma of the pancreas].

PMID- 25857054
TI  - [Nonepithelial neoplasms other than malignant lymphomas (hemangioma,
      lymphangioma, leiomyosarcoma, malignant fibrous histiocytoma, paraganglioma,
      etc)].

PMID- 25857055
TI  - [Clinical guidelines of pancreatic cancer 2013: a synopsis].

PMID- 25857056
TI  - [Overview of revised international consensus guidelines 2012 for the management
      of IPMN and MCN].

PMID- 25857057
TI  - [FOLFIRINOX, nab-paclitaxel + gemcitabine].

PMID- 25857058
TI  - [Erlotinib, sunitinib, and everolimus].

PMID- 25857059
TI  - [Recent advances in research on familial pancreatic cancer by using the
      registry].

PMID- 25857060
TI  - [Lifestyle and the risk of pancreatic cancer].

PMID- 25857061
TI  - [The social program between medical centers and practicing doctors for the early
      diagnosis of pancreatic carcinoma].

PMID- 25857062
TI  - [Borderline resectable pancreatic ductal adenocarcinoma].

PMID- 25857063
TI  - [Present and future status of therapeutic cancer peptide vaccine therapy for
      patients with pancreatic cancer].

PMID- 25857064
TI  - [Robotic pancreatectomy for pancreatic neoplasms].

PMID- 25857065
TI  - [Carbon-ion radiotherapy for pancreatic cancer].

PMID- 25857066
TI  - [Molecular pathology and carcinogenesis of biliary cancer].

PMID- 25857067
TI  - [Biliary tract and pancreas share developmental process and pathological
      features].

PMID- 25857068
TI  - [Invasion and metastasis of biliary tract cancer].

PMID- 25857069
TI  - [Epidemiology of biliary tract cancer--comparison with other country].

PMID- 25857070
TI  - [Pathological classification of biliary tract carcinoma].

PMID- 25857071
TI  - [Oncogene (K-ras, p53, p16, DPC4, hTERTmRNA)].

PMID- 25857072
TI  - [hENT1, dCK, RRM, WFA-MY.1E12].

PMID- 25857073
TI  - [The excision repair cross-complementation group 1].

PMID- 25857074
TI  - [US].

PMID- 25857075
TI  - [CT and MR imaging of biliary cancer].

PMID- 25857076
TI  - [Role of endoscopic retrograde cholangiography for cancer of the biliary tract].

PMID- 25857077
TI  - [The role of EUS and IDUS for diagnosis of malignant biliary diseases].

PMID- 25857078
TI  - [Imaging diagnosis of biliary tract cancer on PET].

PMID- 25857079
TI  - [PTCS/POCS].

PMID- 25857080
TI  - [Bile cytology for biliary tract cancer].

PMID- 25857081
TI  - [ERCP cytology & biopsy and EUS-FNA for biliary diseases].

PMID- 25857082
TI  - [Epidemiology of gallbladder carcinoma].

PMID- 25857083
TI  - [Risk factors].

PMID- 25857084
TI  - [Clinicopathological features of gallbladder cancers].

PMID- 25857086
TI  - [Current algorithm for the management of gallbladder cancer].

PMID- 25857085
TI  - [Symptoms, physical findings, and laboratory data of gallbladder cancer].

PMID- 25857087
TI  - [Actual diagnosis of gallbladder cancer].

PMID- 25857088
TI  - [The differential diagnosis between gallbladder cancer and other benign lesions].

PMID- 25857089
TI  - [Treatment strategy of the gallbladder cancer].

PMID- 25857090
TI  - [Surgical treatment for gallbladder cancer].

PMID- 25857091
TI  - [Laparoscopic surgery for gallbladder: carcinoma].

PMID- 25857092
TI  - [Current status and future perspective of chemotherapy for gallbladder cancer].

PMID- 25857093
TI  - [Current status and prospects of radiotherapy for gallbladder cancer].

PMID- 25857094
TI  - [Multidisciplinary treatment of gallbladder cancer--biliary and duodenal
      stenting].

PMID- 25857095
TI  - [Palliative medicine for gallbladder cancer].

PMID- 25857096
TI  - [Outcomes of surgical treatment for gallbladder cancer: differences between Japan
      and western countries].

PMID- 25857097
TI  - [Prognostic factors of gallbladder cancer].

PMID- 25857098
TI  - [Epidemiology of cholangiocarcinoma].

PMID- 25857099
TI  - [Risk factors of cholangiocarcinoma].

PMID- 25857100
TI  - [Clinicopathological features of extrahepatic and hilar cholangiocarcinomas].

PMID- 25857101
TI  - [Symptoms, clinical presentation, laboratory findings].

PMID- 25857102
TI  - [Diagnostic algorithm for bile duct carcinomas].

PMID- 25857104
TI  - [Differential diagnosis between cholangiocarcinoma and benign biliary
      strictures].

PMID- 25857103
TI  - [Diagnosis of bile duct carcinomas].

PMID- 25857105
TI  - [Treatment algorithm for bile duct carcinoma].

PMID- 25857106
TI  - [Hilar cholangiocarcinoma].

PMID- 25857107
TI  - [Distal cholangiocarcinoma].

PMID- 25857108
TI  - [Indication for surgery and surgical procedure for intrahepatic
      cholangiocarcinoma].

PMID- 25857109
TI  - [Current status and future directions in chemotherapy for biliary tract
      carcinoma].

PMID- 25857110
TI  - [Current status and future vision of radiation therapy for cholangiocarcinoma].

PMID- 25857111
TI  - [Multimodal therapy (endoscopical stenting bile-duct, duodenum)].

PMID- 25857112
TI  - [Palliative treatments in patients with advanced cholangiocarcinoma].

PMID- 25857113
TI  - [The outcome of surgical treatment for biliary carcinoma: Japanese and Western
      experience].

PMID- 25857114
TI  - [Prognostic factors for biliary tract cancer].

PMID- 25857115
TI  - [Epidemiology of carcinoma of papilla of Vater in Japan].

PMID- 25857116
TI  - [Risk factor of carcinoma of papilla of Vater].

PMID- 25857117
TI  - [Clinicopathological features of carcinomas of the ampulla of Vater's].

PMID- 25857118
TI  - [Clinical findings and laboratory data of ampullary carcinoma].

PMID- 25857119
TI  - [Algorithm for the diagnosis of ampullary cancer].

PMID- 25857120
TI  - [Actual steps for the diagnosis of ampullary cancer].

PMID- 25857121
TI  - [Differential diagnosis of neoplasm of the papilla of Vater].

PMID- 25857122
TI  - [Treatment algorithm of ampullary carcinoma].

PMID- 25857123
TI  - [Surgical indication and operative method of ampullary carcinoma].

PMID- 25857124
TI  - [Endoscopic resection of neoplasm of the papilla of Vater].

PMID- 25857125
TI  - [Present status and future prospect of the chemotherapy for ampullary cancer].

PMID- 25857126
TI  - [Endoscopic stenting for ampullary carcinoma].

PMID- 25857127
TI  - [Therapeutic results of carcinoma of the papilla of Vater--a comparison of
      Japanease and overseas results].

PMID- 25857128
TI  - [Prognostic factors associated with the long-term survival].

PMID- 25857129
TI  - [Mucinous adenocarcinoma, signet-ring cell carcinoma].

PMID- 25857130
TI  - [Adenosquamous cell carcinoma of the pancreas].

PMID- 25857131
TI  - [Rare cancer of the biliary tract: squamous cell carcinoma].

PMID- 25857132
TI  - [Undifferentiated carcinoma of the gallbladder].

PMID- 25857133
TI  - [Invasive micropapillary carcinoma of the biliary tract].

PMID- 25857134
TI  - [Carcinosarcoma of the biliary tract].

PMID- 25857135
TI  - [alpha-Fetoprotein-producing tumor].

PMID- 25857136
TI  - [Clinicopathologic characteristics of pancreatic neuroendocrine neoplasm].

PMID- 25857137
TI  - [Mucinous cystic neoplasm (MCN) of the liver].

PMID- 25857138
TI  - [Main revised points of the clinical practice guideline for the management of
      biliary tract and ampullary carcinoma ver.2].

PMID- 25857139
TI  - [Clinical study of new chemotherapy regimen for biliary tract cancer].

PMID- 25857140
TI  - [Pathology of IPNB and BilIN].

PMID- 25857141
TI  - [Life-style and biliary tract cancer].

PMID- 25857142
TI  - [Recent advances of biliary drainage for malignant biliary obstruction].

PMID- 25857143
TI  - [Current status and future perspective of peptide vaccine for biliary tract
      cancer].

PMID- 25857144
TI  - [Cholangiocarcinoma among printing workers].

PMID- 25857145
TI  - [Influence of soil factors on quality of panacis majoris rhizoma].
AB  - OBJECTIVE: To research and screen the soil factors which influenced the quality
      of Panacis Majoris Rhizoma. METHODS: By determining the effective constituent of
      saponin of Panacis Majoris Rhizoma from different habitats, and the soil nutrient
      and heavy metal content, using correlation analysis, stepwise regression analysis
      and other statistical methods to analyze the soil factors on the quality of
      Panacis Majoris Rhizoma. RESULTS: The contents of ginsenoside Ro and
      chikusetsusaponin NVa of samples from different habitats were different, the
      corresponding soil nutrient and heavy metal content were also different. The
      content of ginsenoside-Ro was positively related with the soil pH value (P <0.
      01) and negatively related with the soil available N(P < 0.05). The content of
      chikusetsusaponin IVa was positively related with the soil pH (P < 0.01) and
      copper content (P < 0.05), and negatively with the soil available N(P < 0.05)
      CONCLUSION: Soil factors are the leading factors that influence the quality of
      Panacis Majoris Rhizoma, soil pH and soil available N were the dominating
      factors.

PMID- 25857146
TI  - [Effects of low-light stress on photosynthetic characteristics of Paris
      polyphylla var. chinensis in artificial domestication cultivation].
AB  - OBJECTIVE: To decide on the optimum artificial domestication cultivation light
      environment for Paris polyphylla var. chinensis through investigating the effect
      of light intensity on leaf's gas exchange parameters, photosynthetic parameters,
      light saturation point and compensation point of Paris polyphylla var. chinensis.
      METHODS: Different low-light stress gradients' effect on the growth of Paris
      polyphylla var. chinensis was compared with no low-light stress treatment through
      calculating leaf's gas exchange parameters, photosynthetic parameters, light
      saturation point and compensation point, and then all these parameters were
      statistically analyzed. RESULTS: Light intensity had significant influence on the
      photosynthetic characteristics of Paris polyphylla var. chinensis. With the
      strengthening of the low-light stress, chlorophyll content, gas exchange
      parameters, photosynthetic parameters P., AQY and light saturation point all
      gradually increased at first, and then decreased. However, both photosynthetic
      parameters Rd and light compensation point firstly decreased and then rose again.
      These results showed that too strong or too weak light intensity affected the
      optimization of photosynthetic parameters of Paris polyphylla var. chinensis. The
      optimal illuminance for each parameter was not completely same, but they could
      all reach a relative ideal state when the shading ranges between 40% and 60%.
      However, photosynthetic parameters deteriorated rapidly when the shading surpass
      80%. CONCLUSION: For artificially cultivating Paris polyphylla var. chinensis in
      Baoxing,Sichuan or the similar ecological region, shading 40%-60% is the optimal
      light environment, which can enhance the photosynthesis of Paris polyphylla var.
      chinensis and promote the accumulation of photosynthetic products.

PMID- 25857147
TI  - [Effect of improving light intensity on physio-biochemistry of Panax ginseng].
AB  - OBJECTIVE: To provide the basis for improving ginseng production by exploring the
      difference of physio-biochemistry of Panax ginseng after increasing light
      intensity. METHODS: Activities of superoxide dismutase( SOD), hydrogen peroxidase
      (CAT), and peroxydase (POD), as well as contents of malondialdehyde (MDA),
      chlorophyll a and b under full-light condition were compared with those in the
      shade in spring and autumn. RESULTS: Activity of three kinds of enzymes in the
      anti-oxidation system (SOD,CAT and POD) were 27.52%, 41.96% and 37.7% higher than
      the shade group, respectively. The content of MDA was 11.23% lower. There had no
      obvious difference on the content of chlorophyll a, but chlorophyll b was
      decreased slightly. CONCLUSION: Increasing the light intensity properly can
      improve the activities of enzyme protection system, and lower the content of MDA,
      which indicates that the increasing of light will provide a theoretic guide for
      high-production technique of Panax ginseng.

PMID- 25857148
TI  - [Inhibition effects of wood vinegar on Alternaria panax and Botrytis cinerea].
AB  - OBJECTIVE: Less fungicides could be used to biocontrol Alternaria panax and
      Botrytis cinerea, this experiment can offer preliminary theory for wood vinegar
      as a botanic fungicide. METHODS: The in vitro inhibition activities of wood
      vinegar on Alternaria panax and Botrytis cinerea were tested by using mycelial
      growth rate method and spore germination method. RESULTS: Inhibition of mycelium
      growth rate to Alternaria panax was 100% when the concentration of wood vinegar
      was no less than 3.0%, while the inhibition of mycelium growth rate and spore
      germination rate were 70.68% and 84.47%, respectively, at concentration of wood
      vinegar 2.25%. Inhibition of mycelium growth rate and spore germination rate to
      Botrytis cinerea were 100% when the concentration of wood vinegar was no less
      than 2.25%. CONCLUSION: Wood vinegar concentration of no less than 2.25% can be
      used as a biocontrol agent of Alternaria panax and Botrytis cinerea, it is useful
      for the further field trial.

PMID- 25857149
TI  - [Establishment and preliminary analysis of two-dimensional electrophoresis
      patterns of protein in ginseng callus].
AB  - OBJECTIVE: To establish the two-dimensional electrophoresis (2-DE)maps of callus
      induced from ginseng root,and to provide scientific method and data support for
      the study of secondary metabolites biosynthesis pathways of ginseng. METHODS:
      Total protein was extracted from ginseng callus by three different methods. The
      best protein extraction method of ginseng callus tissue was determined by the
      protein yield, purity and SDS-PAGE protein bands. By using 2-DE technology, the 2
      DE maps of ginseng callus was established. The mass spectrometry and function on
      part of the protein were analyzed using MALDI-TOF-TOF and Swiss-Prot software.
      RESULTS: Modified phenol extraction method (the third method)was the best protein
      extraction method of ginseng callus tissue, and it could obtain a high resolution
      2-DE map. The second method was lesser. The protein quality of the first method
      could not be used for the analysis of 2-DE. 12 protein spots of the second and
      third methods were successfully identified by mass spectrometry. CONCLUSION: This
      study established extraction methods suitable for ginseng callus protein and 2-DE
      patterns.

PMID- 25857150
TI  - [Determination of 22 inorganic elements in different parts of Lantana camara by
      ICP-OES].
AB  - OBJECTIVE: To determine the contents of 22 inorganic elements in different parts
      of Lantana camara by inductively coupled plasma optical emission spectroscopy
      (ICP-OES). METHODS: HNO3-H2 02 digested system was used to completely decomposed
      the organic compounds effectually by microwave digestion. 22 inorganic elements
      such as K, Ca, Mg, Fe, Al, Na, Zn, Mn and Cr were determined by ICP-OES under set
      up working conditions. RESULTS: The contents of K, Ca and Mg were the most in
      different parts of Lantana camrnara; The contents of K, Ca, Mg, Mn, Sr and Cu in
      the leaves of Lantana camara were more than that in the root and the branch. The
      contents of Fe and Na in the root of Lantana camara were more than that in the
      leaves and the branch. The contents of Pb and Cd were higher than the national
      standard and Cr had high content in different parts of Lantana camara.
      CONCLUSION: The determination method is quick, easy and accurate with high
      sensitivity,which can determine the contents of 22 inorganic elements accurately
      in different parts of Lantana camara.

PMID- 25857151
TI  - [Application of entropy-weight TOPSIS model in synthetical quality evaluation of
      Angelica sinensis growing in Gansu Province].
AB  - OBJECTIVE: To investigate the establishment and application methods of entropy
      weight TOPSIS model in synthetical quality evaluation of traditional Chinese
      medicine with Angelica sinensis growing in Gansu Province as an example. METHODS:
      The contents of ferulic acid, 3-butylphthalide, Z-butylidenephthalide, Z
      ligustilide, linolic acid, volatile oil, and ethanol soluble extractive were used
      as an evaluation index set. The weights of each evaluation index were determined
      by information entropy method. The entropyweight TOPSIS model was established to
      synthetically evaluate the quality of Angelica sinensis growing in Gansu Province
      by Euclid closeness degree. RESULTS: The results based on established model were
      in line with the daodi meaning and the knowledge of clinical experience.
      CONCLUSION: The established model was simple in calculation, objective, reliable,
      and can be applied to synthetical quality evaluation of traditional Chinese
      medicine.

PMID- 25857152
TI  - [Biosorption of heavy metals in fluoritum decoction by fungal mycelium].
AB  - OBJECTIVE: To explore the biosorption technology of heavy metals in Fluoritum
      decoction by fungal mycelium. METHODS: Four factors including fungal mycelium
      amount, adsorption time, pH value and temperature were employed to estimate the
      fungal biomass adsorption conditions for removing the heavy metals in Fluoritum
      decoction. Then an orthogonal experimental design was taken to optimize the
      biosorption process, and the removal efficiency was also evaluated. RESULTS:
      Under the optimized conditions of 1.0 g/50 mL Fluoritum decoction, 3 hours
      adsorption time, pH 5.0 and 40 degrees C, a result of 70.12% heavy metals removal
      rate was accomplished with 35.99% calcium ion loss. CONCLUSION: The study
      indicates that removing of heavy metals in Fluoritum decoction through fungal
      mycelium is feasible, and the experiment results can also provide a basis for
      further research on biosorption of heavy metals in traditional Chinese medicine

PMID- 25857153
TI  - [Purgative activity difference and mechanism of raw and processed Rhei Radix et
      rhizoma].
AB  - OBJECTIVE: To investigate the purgative activity difference and mechanism of raw
      and processed Rhei Radix et Rhizoma. METHODS: Mail mice were divided into 9
      groups:normal group (saline), model group, Tongbianling group (1 g/kg), raw Rhei
      Radix et Rhizoma groups (5.00, 2.50 and 1.25 g/kg), processed Rhei Radix et
      Rhizoma groups (5.00, 2.50 and 1.25 g/kg). After oral administration for 5 days,
      the diarrhea experiment and intestinal propelling test were carried out to
      evaluate the purgative effect difference of raw and processed Rhei Radix et
      Rhizoma. Wistar rats were divided into normal group (normal saline), model group,
      Tong-bianling group (0.5 g/kg), raw Rhei Radix et Rhizoma group (1.25 g/kg),
      processed Rhei Radix et Rhizoma group (1.25 g/kg). The changes of levels of
      gastin( GAS), motilin( MTL), vasoactive peptide (VIP), neurotensin (NT),
      somatostatin ( SS), acetylcholinesterase (AchE), substance P(SP) and endothelin
      (ET-1)in blood of the rats and gastin (GAS), motilin( MTL), vasoactive peptide
      (VIP) and neurotensin (NT) in colon of the rats were detected. RESULT: The levels
      of GAS, MTL, VIP, NT, SS, AchE, SP and ET-1 in serum of raw Rhei Radix et Rhizoma
      group, and GAS, MTL and VIP in colon of raw Rhei Radix et Rhizoma group were
      different obviously comparing with the processed one (P < 0.01). CONCLUSION: The
      raw Rhei Radix et Rhizoma and the processed one had obvious differences in
      regulating intestinal gastrointestinal hormone and neurotransmitter. This effect
      may be the reason or one of the reasons for purgative activity difference between
      raw and processed Rhei Radix et Rhizoma.

PMID- 25857154
TI  - [SSR information in transcriptome of Pinellia ternata].
AB  - OBJECTIVE: In order to establish new molecular markers and to design SSR
      primers,the SSR information was analyzed in the transcriptome of Pinellia
      ternata. METHODS: The unigenes in transcriptome were filtered and then redundant
      sequences were removed by the tool of EST-trimmer and cross-match, respectively.
      Meanwhile, the non-redundant unigenes were examined by the tool of MISA. RESULTS:
      14,468 SSRs were found, and these SSRs were distributed in 12 000 unigenes in the
      examined sequences. Frequency of occurrences for SSRs was 16.24%, and density of
      distribution was on average 1/4.33 kb in the present study. Di-nucleotide and tri
      nucleotide were the major repeated types,accounting for 51.15% and 41.50%,
      respectively. AG/CT and CCG/CGG were most frequent motifs in di-nucleotide and
      tri-nucleotide, accounting for 41.54% and 11. 84%, respectively. 87.14% motifs in
      the length ranged from 12 bp to 20 bp. CONCLUSION: The SSR site in the
      transcriptome of Pinellia ternata have the characteristics of high frequency of
      occurrences, type richness, high density and high potential of polymorphism, and
      these characteristics might be applied in the study on genetic diversity, marker
      assisted breeding,and genetic map of Pinellia ternata.

PMID- 25857155
TI  - [Study on HPLC fingerprint of miao medicine Ardisia japonica].
AB  - OBJECTIVE: To establish the HPLC fingerprint of Ardisia japonica. METHODS: HPLC
      analysis was performed on a Diamonsil C18 column (250 mm x 4.6 mm, 5 microm) with
      the eluting system of gradient consisted of methanol-0.1% H3PO4. The flow rate
      was 1.0 mL/min. The column temperature was maintained at 35 degrees C and the
      detection wavelength was 250 nm. RESULTS: The HPLC fingerprint was established
      and 10 batches of samples with 32 common peaks were compared. Four peaks were
      identified as gallic acid, bergenin, chlorogenic acid and quercitrin. CONCLUSION:
      The method with good reproducibility is simple and accurate, which can be used
      for determination of HPLC fingerprint and quality control of Ardisia japonica. It
      provides scientific basis of future study of Ardisia japonica.

PMID- 25857156
TI  - [Establishing quantitative model of naringin in citrus Grandis Exocarpium by near
      infrared spectroscopy].
AB  - OBJECTIVE: To establish the quantitative model of naringin in Citrus Grandis
      Exocarpium by near infrared reflectance spectroscopy(NIRS). METHODS: NIRSs of 54
      Citrus Grandis Exocarpium samples were collected and pretreated by TQ Analyst 8.0
      software with first derivative + Norris filter. The wavebands in 10,000-4000 cm(
      1) were collected and 9 numbers of factors were used. The calibration model was
      built with partial least squares (PLS). RESULTS: The quantitative calibration
      model had good correlation coefficients (r = 0.9927) and low root mean square
      error of calibration (RMSEC = 0.0746). Root mean square error of prediction
      (RMSEP) was 0.282. The average rate of recovery of validation was 101.65% (n =
      9). CONCLUSION: The quantitative calibration model is trustworthy and it can be
      used to predict naringin in Citrus Grandis Exocarpium accurately. This simple,
      fast and non-destructive advantages of NIRS can be used for quality control and
      exploitation of Citrus Grandis Exocarpium.

PMID- 25857157
TI  - [Chemical constituents of Acori Calami Rhizoma from Hunan Province].
AB  - OBJECTIVE: To study the chemical components from the ethanol extract of Acori
      Calami Rhizoma from Hunan Province. METHODS: Components were isolated and
      purified through various chromatographic methods and recrystallization, and
      identified by spectroscopic data. RESULTS: Ten compounds were isolated and
      identified as follows: heptadecanoic acid(1), monopentadecanoin(2), syringic
      acid(3), aurantiamide acetate(4), monononadecanoin(5),tatarine A(6),tatanan
      C(7),cerevisterol(8),2 ,6-dioxopiperidin-3-yl acetate(9) and palmatine(10).
      CONCLUSION: Compounds 1-5 and 8-10 are isolated from Acorus genus for the first
      time, and compounds 1-5 and 7-10 are isolated from this plant for the first time.

PMID- 25857158
TI  - [Chemical constituents of Clerodendrum trichotomum Leaves].
AB  - OBJECTIVE: To investigate the chemical constituents of the leaves of Clerodendrum
      trichotomum. METHODS: The chemical constituents of petroleum ether extract of the
      leaves of Clerodendrum trichotomum were isolated and purified by various
      chromatographic techniques, such as silica gel, ODS, Sephadex LH-20, semi
      preparative HPLC and recrystallization. The structures of these isolated
      compounds were identified by spectroscopic analysis (1 H-NMR,13 C-NMR,2D-NMR and
      MS). RESULTS: Ten compounds were isolated and identified from petroleum ether
      extract, containing four triterpenes, lupeol(1), friedelin(2), betulinic acid(3)
      and taraxerol(4); four sterols, 22-dehydroclerosterol(5), clerosterol(6),
      stigmasterol(7) and sitosterol(8); one diterpenoid, transphytol(9), and one
      alkaloid, 1H-indole-3-carboxylic acid(10). CONCLUSION: Compound 10 is obtained
      from the genus Clerodendrum for the first time, and seven compounds (1,3-4, and 7
      10) are firstly isolated from this plant.

PMID- 25857159
TI  - [Chemical constituents of Polygala tenuifolia root].
AB  - OBJECTIVE: To study the chemical constituents from the root of Polygala
      tenuifolia. METHODS: Silica gel,Sephadex LH-20 and ODS chromatographic techniques
      were used to study the chemical constituents of Polygala tenuifolia, and the
      chemical structures were elucidated by application of spectral data. RESULTS:
      Eight-compounds were obtained and their structure were identified as 7-hydroxy-1
      methoxy-2,3-methylenedioxyxanthone(1), 1, 7-dihydroxy-2, 3-dimethoxyxanth one(2),
      1,3,6-trihydroxy-2, 7-dimethoxyxanthone(3),7-hydroxy-1,2, 3
      trimethoxyxanthone(4), 1,2,3,6, 7-pentamethoxyxanthone(5), 1,3, 7-trihydroxy-2, 6
      dimethanoxyxanthone (6),7-hydroxy-1-methoxyxanthone(7) and 1,7-dihydroxy-3,4
      dimethoxyxanthone(8). CONCLUSION: Compounds 1,6,7 and 8 are isolated from
      Polygala tenuifolia for the first time.

PMID- 25857160
TI  - [Chemical constituents of Scrophularia ningpoensis root].
AB  - OBJECTIVE: To investigate the chemical constituents from Scrophularia ningpoensis
      root. METHODS: The compounds were isolated and purified by silica gel and
      Sephadex LH-20 column chromatography. The structures of these compounds were
      elucidated on the basis of spectroscopic analysis. RESULTS: Eleven compounds were
      isolated and identified as vanillin (1), eugenol (2), isoeugenol methyl ether(3),
      ferulic acid(4), benzoic acid(5), syringic acid(6) ,rhamnopyranosyl vanilloyl(7),
      syringic acid-4-O-alpha-L-rhamnopyr-anoside(8), beta-sitosterol(9), adenosine
      (10) and dibutyl phthalate(11). CONCLUSION: Compound 1-3 and 6-8 are obtained
      from this plant for the first time.

PMID- 25857161
TI  - [Study on chemical constituents of Toddalia asiatica].
AB  - OBJECTIVE: To investigate the chemical constituents of Toddalia asiatica.
      METHODS: The compounds were isolated and pu- rified by column chromatography and
      their structures were identified on the basis of physicochemical properties and
      spectral data analysis. RESULTS: Sixteen compounds were isolated and identified
      as zanthocadinanine A(1), pimpinellin(2), isopimpinellin(3), phellopterin (4),
      armottianamide(5), chelerythrine(6), nitidine(7), chlorogenic acid (8),
      toddalolactone (9), protopine(10), skimmianine(11), dictamine(12),
      toddalenone(13), beta-sitosterol(14), bergapten(15) and 8-hydroxy-6
      methoxycoumarin(16). CONCLUSION: Compound 1 and 16 are isolated from Toddalia
      genus for the first time.

PMID- 25857162
TI  - [Determination of lignanoids in seeds of Schisandra chinensis by combinative
      methods of fingerprint and QAMS].
AB  - OBJECTIVE: To establish a fingerprint of seeds of Schisandra chinensis (SSC) and
      develop a method of quantitative analysis of multi-components by single marker
      (QAMS) for simultaneous determining six lignanoids in SSC. METHODS: Eleven
      batches of SSC were determined by HPLC and a common mode of fingerprint has been
      established. A method was developed for QAMS to determine schizandrol A,
      schizandrol B, schisantherin A, deoxyschizandrin, schizandrin B and schizandrin C
      in SSC. Schizandrol A was selected as internal reference; the relative correction
      factors (RCF)of other five lignanoids to the internal reference were calculated.
      The contents of the six lignanoids in eleven batches of SSC were determined by
      both external standard method and QAMS. The QAMS method was evaluated by
      comparison of its assay results with that of external standard method. RESULTS:
      There were 24 common peaks in fingerprints of eleven batches of SSC, six of them
      were identified. The similarities of fingerprints of eleven batches of SSC were
      over 0.980. The established RCF had a good reproducibility. No significant
      differences were found between the quantitative results of external standard
      method and QAMS. CONCLUSION: The developed method is accurate,feasible, and can
      be used for the qualitative and quantitative analysis of lignanoids in SSC.

PMID- 25857163
TI  - [Study on binding forms of selenium in selenium-enriched Salvia miltiorrhiza].
AB  - OBJECTIVE: To understand the absolute and relative concentrations of
      proteins,polysaccharides and nucleic acids that are Selenium-binding in Selenium
      enriched Salvia miltiorrhiza, and to determine the efficiency of
      biotransformation of inorganic Selenium compounds in Salvia miltiorrhiza.
      METHODS: Extract the Selenium-binding proteins, polysaccharides and nucleic acids
      in Selenium-enriched Salvia miltiorrhiza using different solvents. Determine the
      concentrations of proteins, polysaccharides and nucleic acids by
      spectrophotometry, the concentration of Selenium by Hydride generation atomic
      fluorescence spectrometry. RESULTS: Selenium-binding proteins took up 74.2% of
      the total amount of Selenium in the tested Salvia miltiorrhiza, while Selenium
      binding polysaccharides took up 39.5% and Selenium-binding nucleic acids took up
      2.3%. Selenium that was bound with the water-soluble proteins came out as the
      most con- centrated, taking up 46.0% of the total amount of Selenium, during the
      extraction of Selenium using water, NaCl, ethanol and NaOH solution,
      respectively. Being extracted by the weak acid and alkali phosphoric acid buffer
      solutions, Selenium-binding proteins were more concentrated in the alkali buffer
      solution, taking up 51.2% of the total amount. CONCLUSIONS: In Salvia
      miltiorrhiza, Selenium exists mainly in the forms of selenium-binding proteins
      and Selenium-binding polysaccharides. Cultivation of Selenium-enriched Salvia
      miltiorrhiza achieves the biotransformation of inorganic Selenium compounds into
      organic compounds efficiently.

PMID- 25857164
TI  - [Study on hypoglycemic effect and mechanism of total flavonoids of Propolis in
      STZ diabetic rats].
AB  - OBJECTIVE: To study hypoglycemic effect and mechanism of the total flavonoids of
      Propolis (TFP) in the STZ diabetic rats. METHODS: The model of type 2 diabetic
      rats was induced by high-fat diet feeding for 4 weeks combined with
      intraperitoneal injection of streptozotocin (STZ). Then the rats without above
      mentioned treatment were selected as the normal control group,the diabetic rats
      were randomly divided into four groups by blood glucose, the model control group,
      high doses (240 mg/kg), medium doses (120 mg/kg) and low doses (60 mg/kg) TFP
      groups. The TFP preparation was intragastric administration given to rats in TFP
      groups. The model control rats were treated intragastric administration with 0.5%
      sodium carboxymethyl cellulose (CMC-Na) for 4 weeks. The rats were fed with high
      fat diet during treatment. 12 hours after the last administration, glucose (GLU),
      total cholesterol (TC), triglyceride (TG), high density lipoprotein( HDL-C), low
      density lipoprotein LDL-C), glycated hemoglobin (GHb), serum insulin INS), C
      peptide (C-P), superoxide dismutase( SOD), malondialdehyde (MDA), glutathione
      (GSH), tumor necrosis factor-alpha (TNF-alpha), free fatty acid (FFA), nitric
      oxide (NO), and hepatic glycogen were determined. RESULTS: Compared with the
      normal group, the levels of GLU, TC, TG, HDL-C, FFA, TNF-alpha, NO, MDA and GHb
      in serum were increased significantly in the model control group (P < 0.05-P <
      0.001), the levels of HDL-C, INS, C-P, SOD and GSH in serum and hepatic glycogen
      in hepatic tissue were decreased significantly (P < 0.01 or P < 0.001). The
      levels of all above indexes of high and medium doses groups were improved
      significantly compared with the model control group (P < 0.05-P < 0.01).
      CONCLUSION: TFP can significantly decrease the level of blood glucose,improve the
      glucose and lipid metabolism and inhibit insulin resistance in STZ diabetic rats.

PMID- 25857165
TI  - [Comparative study on pharmacokinetics and tissue distribution of cis- and trans
      2,3,5,4'-Tetrahydroxystilbene-2-O-beta-D-glucosides in mice].
AB  - OBJECTIVE: To develop a method for simultaneous determination of cis-2,3,5,4'
      tetrahydroxystilbene-2-O-beta-D-glucoside (cis-THSG) and trans-2,3,5,4'
      tetrahydroxystilbene-2-O-beta-D-glucoside (trans-THSG) in mice and comparative
      study of cis-THSG and trans-THSG in pharmacokinetic and tissue distribution.
      METHODS: Analyses was performed using a Diamonsil C,18 (250 mm x 4.6 mm, 5
      microm) column with acetonitrile-methanol-0.1% acetic acid (11:7: 82) as the
      mobile phase at a flow rate of 1.0 mL/min. Polydatin was took as the internal
      standard. The detection wavelength was set at 285 and 320 nm. RESULTS: Intra-day
      and inter-day RSD were less than 9.47%. The recoveries and stabilities( RE) were
      ranged from -9.69% to 4.18% and from -9.49% to 1.33%, respectively. The
      pharmacokinetic parameters showed that the elimination half-life of cis-THSG was
      longer than that of trans-THSG and the biological availability of cis-THSG was
      higher than that of trans-THSG. Both cis-THSG and trans-THSG were widely
      distributed in the tissues. At the same dosage,the tissue concentrations of trans
      THSG were greater than those of cis-THSG. CONCLUSION: The method is
      specific,sensitive, simple, rapid and suitable for simultaneous determination of
      cis-THSG and trans-THSG in mice. The results of pharmacokinetic and tissue
      distribution indicated that there was significant difference between cis-THSG and
      trans-THSG in vivo.

PMID- 25857166
TI  - [Protective effects of CVB-D on cardiac myocytes injury induced by high
      sympathesis activity in vitro].
AB  - OBJECTIVE: To investigate the protective effect of CVB-D on cardiac myocytes
      injury induced by high sympathesis activity and its relationship with oxidative
      stress. METHODS: Primary culture cardiac myocyte of new-born rat was injuried by
      NE and then incubated with VE and CVB-D (10 and 50 micromol/L). Indexes of
      cardiac myoctye injury were assayed by morphologic change, MTT, and LDH leakage
      ratio. The activity of SOD and the content of MDA were investigated to identify
      oxidation and antioxygen. RESULTS: CVB-D (10 and 50 micromol/L) significantly
      increased the cell survival rate,and reduced the LDH leakage rate. CVE-D (50
      micromol/L) significantly increased the activity of SOD, and decreased content of
      MDA in injuried cell. CONCLUSION: CVB-D has protective effect against myocardial
      injury induced by high sympathesis activity, the mechanism involves in
      ameliorating oxidative stress.

PMID- 25857167
TI  - [HPLC determination of four flavonoids in rat plasma after oral ecliptae herba
      extract].
AB  - OBJECTIVE: To establish an HPLC method for determination of four flavonoids in
      rat plasma after oral Ecliptae Herba extract. METHODS: HPLC separation was
      carried out in a Neocleodur 100-5 C18 column (250 mm x 4.6 mm, 5 microm) with
      mobile phase A (consisting of methanol-0.2% phosphoric acid = 50:50) and mobile
      phase B (acetonitrile)with gradient elution at the flow rate of 1.0 mL/min. The
      detection wavelength was 350 nm and the column temperature was maintained at 40
      degrees C. RESULTS: There were good linear relationships between concentration
      and peak area ratio of luteolin, apigenin, scutellarein and diosmetin in the
      ranges of 0.02-50 microg/mL with the recovery rates of 71.5%-90.2%. CONCLUSION:
      This method is rapid, accurate and reproducible for determination of luteolin,
      apigenin, scutellarein and diosmetin in rat plasma and study on pharmacokinetics
      of Ecliptae Herba extract.

PMID- 25857168
TI  - [Intervention of Tibetan medicine--twenty wei chenxiang pill on elevation of
      hypoxic pulmonary arterial pressure in rats].
AB  - OBJECTIVE: To investigate the role of Tibetan medicine-Twenty Wei Chenxiang Pill
      interfering with serum ET-1 level, in order to confirm that ET-1 is involved to
      the pathogenesis of hypoxic pulmonary hypertension. METHODS: 165 Wistar rats were
      randomly divided into high altitude control group,Tibetan medicine-Twenty Wei
      Chenxiang Pill group and plain control group. The physiological signal
      acquisition system was used to record pulmonary arterial pressure, and RV/(LV +
      S) ratio were caculated. Serum HIF-1alpha and ET-1 protein levels were determined
      by the method of ELISA, and ETA protein levels in lung tissue were determined by
      Western Blot method. RESULTS: Compared with the high altitude group,in the rats
      of Tibetan medicine-Twenty Wei Chenxiang Pill group,the pulmonary arterial
      pressure decreased significantly from the seventh day and the seventh day (P <
      0.01), the RV/(LV + S) ratio and serum HIF-1alpha levels decreased significantly
      from the third day (P < 0.05 or P < 0.01), the serum ET-1 levels decreased
      significantly from the third day (P < 0.05 or P < 0.01), and the expression of
      ETA protein decreased significantly from the beginning (P < 0.01 or P < 0.001).
      CONCLUSION: ET-1 is one of the important factors causing pulmonary artery
      pressure increasing and right ventricular wall thickening, which plays a role in
      hypoxic pulmonary artery only involved in the early period hypoxia, but not in
      the later period. Tibetan medicine--twenty Wei Chenxiang Pill can prevent the
      pulmonary artery hypertension and the right ventricular wall thickening in rats,
      and its mechanism may be related to the direct inhibition of ET-1 and protein
      levels of ETA or the indirect downregulation of ET-1 level and ETA through
      inhibition of HIF-la level.

PMID- 25857169
TI  - [Preparation technology optimization of xiaozhong cataplasm by central composite
      design-response surface method and preliminary clinical effect evaluation].
AB  - OBJECTIVE: To optimize the preparation technology of Xiaozhong Cataplasm and to
      evaluate its preliminary clinical effect. METHODS: The viscosity, residue and
      appearance were selected as evaluation indexes. The central composite design
      response surface methodology was applied to optimize the amounts of Skeleton
      material, tackifier and crosslinking agent. Clinical effect of Xiaozhong
      Cataplasm was observed. RESULTS: The optimal formulation was HQ841: PVP k120:
      PVPP: aluminium glycinate: water: glycerin: ethanol = 4:3:2:0.15: 60:25:10. The
      effective rate of the cataplasm was 97.22% and 91.67% had marked effect.
      CONCLUSION: Prepared by the optimal preparation technology, the cataplasm has the
      moderate viscosity and little residue with good clinical effect.

PMID- 25857170
TI  - [Extraction technology optimization of huoxuehuayu granules].
AB  - OBJECTIVE: To optimize the extraction process of Huoxuehuayu granules. METHODS:
      To determine the activities of serum creatine kinase (CK) and lactate
      dehydrogenase (LDH) of experimental myocardial ischemia mice, in order to
      optimize the best extraction technology of Huoxuehuayu prescription. According to
      the pharmacological results,with composite score of extraction rate of tanshinone
      II(A) and dry extract rate as comprehensive evaluation indexes, orthogonal test
      was used to optimize the ethanol extraction technology by taking ethanol
      concentration, the amount of ethanol, extraction time and soaking time. With
      extraction rate of salvianolic acid B and dry extract yield as comprehensive
      evaluation indexes, effect of extraction times, the amount of water, and
      extraction time on water extraction technology were investigated by orthogonal
      test. RESULTS: Optimum ethanol extraction technology conditions were as follows:
      extracted once with ten times the amount of 80% ethanol, 1.5 h. Optimum water
      extraction technology conditions were as follows: extracted three times with
      eight times the amount of water, 1 h each time. The best ethanol precipitated
      technique was the relative density of the liquor to be condensed to 1.20 (60
      degrees C), adding 95% ethanol to 80% of ethanol concentration and depositing for
      24 h. CONCLUSIONS: Optimized extraction technology is simple, stable and
      feasible,which can settle foundation for molding technology of Huoxuehuayu
      granules.

PMID- 25857171
TI  - [Ti-AI intermetallic compound membrane refining Chinese medicinal materials
      extract].
AB  - OBJECTIVE: To preliminarily evaluate the refining effect on Chinese medicinal
      materials extract using the microfiltration membrane of Ti-A1 intermetallic
      compound. METHODS: Conduct a series of microfiltration experiments on the extract
      of several commonly used Chinese medicinal materials (Nelumubinis Plumula and
      Eucommiae Folium)and compound preparation of Baihuasandi. Then, analyze the
      changes of traits, total solid and index components before and after filtring.
      RESULTS: After two stages (10 microm and 30 microm) of membrane micro-filtring,
      the total solid removal rates of Nelumubinis Plumula were 1.2% and 22.66%, and
      the remaining rates of neferine were 97.56% and 95.12%; The total solid removal
      rates of Eucommiae Folium were 1.2% and 22.66%, and the remaining rates of
      caffeotannic acid were 95.50% and 87.28%; The totalsolid removal rates of
      Baihuasandi were 11.09% and 14.29%, and the remaining rates of quercetin were
      98.58% and 95.43%, respectively. CONCLUSION: Microfiltration membrane technique
      utilizing the Ti-Al intermetallic compound has a good effect in refining Chinese
      medicinal materials extract.

PMID- 25857172
TI  - [The analysis of fMRT answer's individual variability at healthy examinees when
      opening eyes, motor and speech tests].
AB  - This paper analyzes the variation of the functional anatomy of the brain in
      healthy people performing identical activities on the basis of functional
      magneticresonance imaging (fMRI). According to the authors, this approach allows
      you to showcase a variety of individual strategies to achieve the same external
      (behavioral) result intracerebral different means, and to identify the factors
      that determine this diversity. Investigated hemodynamic (fMRT) brain reactions at
      activization of attention to opening of eyes, motor (search of the right and left
      hand fingers) and speech tests (mental transfer of months or days of the week
      upside-down) at 21 healthy subjects (21-30 years): 14 men, 7 women. Certain
      variety of fMRT answers is revealed: 3-4 jet types of hemodynamic changes were
      allocated for test in group, and the percent of supervision of each type
      fluctuated from 40 to 10%. Shown marked gender differences responses which
      specificity is determined by the nature of the functional load. In motor and
      speech tests, performed with his eyes closed, fMRI response in women is
      characterized by greater specificity and locality than in men. At motor tests
      fMRT answers of men are accompanied big, than at women, inclusion in reaction of
      frontal areas of the cortex, providing realization of regulatory functions. When
      opening of eyes the women's fMRT responses, on the contrary, become more
      diffusion, and men's--more local.

PMID- 25857173
TI  - [Reorganization of the system activity of the brain by understanding of the
      meaning of visually presented texts with increasing completeness of the
      information].
AB  - The present paper investigates the study of features of brain activity by the
      process of change the regimes of information associated with the stages of
      understanding of the meaning of visually presented texts in adult subjects (n =
      148). Researchers have developed an original methodology of step-by-step
      presentation of the texts. This technology has allowed the researchers "to catch"
      a psycho-physiological markers of understanding and identify the stages in a
      temporal sequence of the process of understanding. EEG data was analysed using
      spectral and non-linear methods. Was highlighted three stages: "before
      understanding", "understanding" and "after understanding". The study discovered
      the phenomenon of V- shaped changes to the values of the fractal dimension of
      EEG. The first stage is characterized by the increasing of the power spectrum of
      EEG in the high frequency range and increase the value of the fractal dimension
      of EEG, what probably reflects the process of the generation of ideas and the
      search of solutions. At the next stage ("understanding") a decrease in the value
      of the fractal dimension of EEG was registered, and an increase of the power
      spectrum of the low-frequency range. This seems to reflect the simplification of
      the invariance of reality to the only valid alternative. The last stage is
      characterised by the increasing power spectrum of EEG in the high frequency range
      and increase the value of the fractal dimension of EEG, which can reflect the
      process of intensification of activity of the brain associated with the
      verification of the correctness of the decision. The results obtained allow an
      approach to the understanding of the physiological mechanisms of the
      reorganization of the system of brain activity in the process.of understanding of
      the meaning of visually presented texts. This, therefore, outlines the path to
      the elimination of existing contradictions in the literature relating to the role
      of high- and low-frequency components of the EEG as markers of the state of
      understanding.

PMID- 25857174
TI  - [Functional interactions between caudate nuclei and inferior frontal gyrus in
      deliberate deception processing].
AB  - The present paper dedicated to the research of the functional interactions
      between brain structures while executing deliberate deceptive actions. Based on
      our own and literature data, we formulated the hypothesis that the functional
      interaction between brain areas responsible for the executive control, localized
      in the prefrontal cortex (inferior frontal gyrus), and the elements of error
      detection brain system, underlies deception. To test this hypothesis, we applied
      an analysis of the psychophysiological interaction (PPI), which revealed that the
      false actions (in comparison with true honestones) associated with increased
      functional connectivity between the left caudate nucleus and the left inferior
      frontal gyrus. Obtained experimental data support our hypothesis that the
      interaction of neural brain systems, which are responsible for executive control
      and error detection, underpins the brain maintenance of the execution of
      deceptive actions.

PMID- 25857175
TI  - [The brain structures functional activity and aggression patients' multiple
      sclerosis].
AB  - The article is devoted to investigation of unconscious aggression in patients
      with multiple sclerosis. We carried out comparison of the relative assessments of
      metabolism speed of glucose (according to positron emission tomography) and
      indicators of unconscious aggression (in the Hand test). It is shown that an
      increased tendency to open aggression (unconscious aggression) in patients with
      multiple sclerosis, is mainly linked with a reduction in the functioning of
      different departments of the frontal lobes of the brain on the left and with
      changes of the metabolism speed of glucose in the structures of the limbic system
      of the left and right hemisphere. With increasing of unconscious aggression we
      observed decrease of glucose metabolism speed in certain areas of the lower and
      middle frontal gyrus.

PMID- 25857177
TI  - [The distinctive features of EMG-activity in early age children with movement
      disorders].
AB  - The purpose of this work was the study of neuromuscular characteristics of
      healthy infants and infants with movement disorders by method of surface
      electromyography. 76 children at the age from 6 months till 3 years participated
      in the investigation: 61 with movement disorders (13--with ataxic form of
      cerebral palsy (CP), 48--with spastic form of CP) and 15 without movement
      disorders. Passive flexing and extending of knee and hip joints was conducted to
      the child in a recumbent position, EMG activity of the basic muscles groups of a
      hip and a shin was recorded. Characteristic properties of electromyographic
      activity were assessed with wavelet transform and subsequent analysis of obtained
      time dependencies. As a result of work the parameters connected with diagnosis of
      infants with movement disorders were revealed.

PMID- 25857176
TI  - [Features of the spatial organization of EEG manifestations in different variants
      of anxiety symptoms in patients with depression].
AB  - Investigations were carried out on 36 patients with reactive depressive states
      and repeating depressive episodes with severe manifestation of anxiety syndrome.
      The spatial organization of brain activity by cross-correlation analysis was
      studied. Shown, that clinical depression and anxiety syndrome is reflected in the
      structure of the spatial organization of EEG depending on options manifestation
      of anxiety disorder.

PMID- 25857178
TI  - [The influence of the leg load and the support mobility under leg on the
      anticipatory postural adjustment].
AB  - Anticipatory postural adjustment is an essential part of equilibrium maintainance
      during standing in human. So changes in stance condition could affect both
      control of equilibrium and anticipatory adjustment. Anticipatory changes in the
      stabilogram of each leg were studied in standing subject during the early stage
      of quick right arm lifting while legs were on two separated supports. The center
      of pressure (CP) movement was analyzed in three variants of experiment: both legs
      on immovable support, with only right leg on the movable support and with only
      left leg on the moveable support. In each standing condition subject stood with
      symmetrical load on two legs or with the load voluntary transferred to one leg.
      The anticipatory CP shift depended on the mobility of the support under the leg
      and on loading of the leg. While standing on unmovable supports with symmetrical
      load on the legs before lifting of the right arm CP of right leg shifted backward
      and CP of left leg--forward. While standing with one leg on movable support the
      anticipatory CP shift of this leg was small and did not depend on the load on the
      leg. However the shift of CP of the leg that was placed on the unmovable support
      depended on the load in the same way as in the case when both legs were on
      unmovable supports. Results suggested that since on movable support the support
      and proprioceptive afferent flow from distal part of the leg that was did not
      supply unambiguous information about body position, the role of distal joints in
      posture control is reduced.

PMID- 25857179
TI  - [Estimation of bronchial tree zones involved in formation of human forced
      expiratory wheezes through vortex shedding mechanism, depending on the dynamic
      compression of central airways].
AB  - Forced expiratory wheezes (FEWs) are examined for the diagnosis of pulmonary
      disease. However there is no clarity in the mechanisms and possible localization
      of their formation. Purpose--Clarification of the formation of FEWs in bronchial
      levels in different types of dynamic compression. Peak frequency mid-frequency
      (400-600 Hz) of FEWs of maximum power and peak frequency of high frequency FEWs
      (600 Hz) of maximum power and speed of the flow at the mouth were measured in the
      sample of 85 healthy male volunteers (16-23 years). Strouhal coefficients were
      calculated for variuow levels of bronchial tree according to Weibel's
      morphometry. It is shown that for FEWs, formed by the vortex shedding with
      Strouhal coefficients of 0.2-0.3, the trend is shifting their formation zone to
      the proximal region with increase of dynamic compression of the airways. The most
      reliable estimates of dynamic compression result in formation of mid-frequency
      FEWs in the area of exit of intrathoracic portion of trachea into its outer part
      and in bifurcation of trachea, while the most probable formation zone of early
      high FEWs are bifurcations of trachea and main bronchi.

PMID- 25857180
TI  - [Basic mechanisms of QRS voltage changes on ECG of healthy subjects during the
      exercise test].
AB  - Electrocardiography is the most commonly used technique for detection stress
      induced myocardial ischemia. However, the sensitivity of ECG-criteria is not
      high. One of the major problem is the difficulty in differentiating ECG changes
      caused by various factors. The aim of this study was to evaluate the dependence
      of the QRS voltage changes during exercise on parameters of central hemodynamics,
      gender particularities and to reveal mechanisms causing these changes. To
      eliminate the effect of changes in cardiomyocytes transmembrane potentials under
      the influence of the neurotransmitters of the autonomic nervous system during
      stepwise increasing exercises and/or due to a lack of ATP results from inadequate
      myocardial blood flow only healthy subjects not older than 35 years were included
      in the study (7 men and 7 women) and only periods of ventricular depolarization
      (QRS complex on the ECG) were included in the analysis. We compared the changes
      of QRS waves during exercise sessions with two upper and one lower limbs in both
      men and women. The exercise load was twice bigger in exercise with one leg
      relative to exercise with two arms. Responses of heart rate and systolic arterial
      pressure were similar. Amplitude of S-wave in left chest leads significantly
      increased in both sessions without significant difference between augmentations
      in the sessions and in groups of men and women. Significant relationship between
      the S wave augmentation and the peak systolic arterial pressure were revealed.
      Furthermore, the QRS changes during the exercise with vertical and a horizontal
      torso position were compared to assess the impact of diastolic arterial pressure
      and displacement of the diaphragm and heart rotation due to increase of abdominal
      pressure during the last steps of exercise. The obtained results allow us to
      exclude the impact of the heart position and size changes, as well as the
      exercise load on S-wave changes and make a conclusion about the dependence of
      this parameter on the value of systolic blood pressure.

PMID- 25857181
TI  - [Features of psychophysiological status in adolescents with different intensity
      of sporting hours].
AB  - The experimental study of psychophysiological parameters of the central nervous
      system (CNS) has been performed in the adolescents who combine the learning
      educational and sporting activities. The differences in psychophysiological
      indices in dependence on the intensity level of sporting loads have been revealed
      in the trained and non-trained adolescents in the presence of similar genetically
      determined abilities which may be determined by the force of the nervous system.
      The psychophysiological profile of.the youths and girls with a high intensity of
      sporting loads is characterized by the balance of nervous processes, the optimal
      functional state of CNS. The significantly higher speed of visual-motor reaction
      were revealed to be in the person with a high intensity of sporting loads than in
      moderate and low intensity of sporting loads. The psychophysiological profile in
      the adolescents with a low and moderate intensity of sporting loads in differed
      by disbalance of nervous processes with prevalence of the braking processes, a
      low speed of visual-motor reaction as the functional state of CNS is
      characterized by the pathological declinations. The attention level was found to
      reach the average values in the teenagers examined independently of intensity of
      sporting loads.

PMID- 25857182
TI  - [Effect of exhaustive weightlifting exercise on EMG, biochemical markers of
      muscle damage and performance capacity in young male subjects].
AB  - The aim of this study was to examine the effect of exhaustive weightlifting
      exercise on electrical and biochemical variables and performance capacity in
      young male subjects. The onset of exercise (80-50% 1RM) was associated with a
      decrease in the amount of work performed, which was followed by a steady
      performance capacity at 40-10% 1RM. There were no significant changes of m.
      rectus femoris EMG maximal amplitude though it tended to be increased during the
      first half of exercise. A significant blood lactate concentration increase
      indicated that an anaerobic metabolism was a predominant mechanism of muscle
      contraction energy-supply. CK level in blood plasma did not change but plasma
      myoglobin concentration doubled immediately post-exercise. The data presented
      here suggest that decrease in performance capacity was likely due to progressive
      "refusal of work" of the fast motor units and work prolongation of weaker,
      intermediate and slow motor units. Unchangeable CK activity and relatively small
      increase in myoglobin concentration in plasma suggest that used weightlifting
      exercise did not induced substantial damage in myocytes' membranes in our
      subjects.

PMID- 25857183
TI  - [Restoration of contractile capacity of the muscles after closed malleolar
      fractures].
AB  - According to the literature data incomplete restoration of the muscular strength
      is observed after malleolar fractures that made us evaluate the contractile
      capacity of the tibial muscles after treatment of 59 adult patients with these
      fractures using Ilizarov method. Additionally, late follow-up of 5 cases were
      examined in complex. Practically, full restoration of the anatomical sizes,
      electrogenesis and contractile property of the tibial muscles is possible in the
      interval from 5 to 8 years after treatment that can be explained by fine
      reduction and reliable fixation of the bone fragments during treatment and
      increase of neuro-motor apparatus sensitivity to the specific impacts while
      muscles' work in the conditions of habitual motor activity.

PMID- 25857184
TI  - [Endotoxin theory of atherosclerosis].
AB  - The involvement of bacterial lipopolysaccharides in the induction of
      atherogenesis is postulated. The excess of bacterial lipopolysaccharides
      (endotoxin aggression) is observed in the general blood circulation of volunteers
      with the presence of atherosclerotic risk factors (obesity, diabetes, stress,
      pathology of haemostasis, kidney, intestines, etc.). The results allow to be
      optimistic about the prospects for preventing the development and progression of
      atherosclerotic pathology.

PMID- 25857185
TI  - [The study of human pregnancy specific beta1-glycoprotein immunomodulating
      effects].
AB  - Effect of human Pregnancy specific beta1-glycoprotein (PSG) in physiological
      concentrations was analyzed against the expression of natural killer (NK)-, T
      cells with natural killer functions (N KT-) and T-regulatory lymphocyte (Treg)
      markers, as well as on the activity of monocyte indolamine-2,3-dioxygenase (IDO)
      and lymphocyte apoptosis in vitro. It was revealed that PSG in high concentration
      (100 MUg/mL) suppressed the CD16/56 expression by NK-cells, while inhibiting the
      cytolytic activity of these cells. Meanwhile, PSG in low concentrations (1 and 10
      MUg/mL) enhanced the CD16/56 expression by NKT-cells that was related to cytokine
      producing activity. It was found that PSG increased the number of adaptive Tregs
      in culture (CD4+FOXP3+ and CD4+CD25(bright)FOXP3+). In addition, PSG promoted the
      IDO activity in peripheral monocytes, while further potentiating the Treg
      generation. In general, PSG rendered anti-apoptotic action on lymphocytes.
      Therefore, indicated effects can determine the PSG contribution to the
      development of immune tolerance in pregnancy.

PMID- 25857187
TI  - [How pseudoscience is snowballing].

PMID- 25857186
TI  - [Estimation of the renin-angiotensin-aldosterone system, water and electrolyte
      imbalance and endothelial function in newborns of women with chronic
      hypertension].
AB  - The aim of this study was to evaluate the parameters of renin-angiotensin
      aldosterone system, natriuretic peptides, and markers of endothelial function in
      the early neonatal period and at the age of 3 months in 83 full-term infants of
      women with chronic hypertension, there were: 60 newborns from women with chronic
      hypertension of mild to moderate severity (main group) and 23 newborns from women
      without hypertension (comparison group). The levels of the renin angiotensin-II,
      aldosterone, natriuretic peptides, endothelin-1, in cord and peripheral blood
      were determined by immunoassay, the metabolites of stable oxide nitric--by Griess
      method. The newborn of women with chronic hypertension showed a significant
      elevation of renin, angiotensin II and brain natriuretic peptide at birth. A
      statistically significant increase in concentration of atrial natriuretic peptide
      (aANP1-28) was determined to the 3-5 days of life. Significantly high levels of
      renin, angiotensin II, endothelin-1 and decreased levels of endogenous nitrite at
      the age of 3 months of life was found. The results findings suggest that prenatal
      activation of the renin-angiotensin-aldosterone system of the fetus, continuing
      to be in the newborn of women with chronic hypertension during the first three
      months of life. The same infants have the violation of endothelial function to 3
      months of age.

PMID- 25857188
TI  - [Molecular genetics of development of cornea].
AB  - This paper mainly reviews sources discussed in recent years that are devoted to
      the genetics of corneal development. Genetically caused separation processes of
      corneal bud and its specification and differentiation are considered. It is shown
      that mutation disorders in the genes responsible for differentiation of the
      cornea can lead to different forms of dystrophies and other corneal disorders.

PMID- 25857189
TI  - [The birth and death of genes].
AB  - Duplications of DNA regions with subsequent divergence of the duplicated copies
      by mutations is traditionally considered to be the major mechanism of the new
      genes appearance. After duplication, only a small fraction of the paralogs
      remains unchanged, while most copies are converted into pseudogenes or acquire
      new functions as a consequence of either subfunctionalization or
      neofunctionalization events. In some cases, certain regions of duplicated copies
      can combine with each other, giving rise to functionally new genes. Analysis of
      the primate genomes revealed a burst of segmental duplications in apes. It was
      demonstrated that some of these duplications include genes that are specifically
      duplicated only in human. Genome sequencing, followed by transcriptome analysis,
      enabled the identification of transcribed pseudogenes in mammalian genomes, that
      contradicts with the traditional view of pseudogenes as inactive copies of
      functioning genes.

PMID- 25857190
TI  - [Inversion polymorphism of nonbiting midges Camptochironomus tentans (Fabricius),
      1805 (Diptera, Chironomidae) from populations of the Lower Volga region and
      Central Caucasus].
AB  - The karyotype of Camptochironomus tentans (Fabricius), 1805 (Diptera,
      Chironomidae) from the populations of the Lower Volga region and Central Caucasus
      (the northern macroslope) has been studied. In the karyotype of C. tentans from
      Saratov oblast, 14 banding sequences (BS), 13 genotypic combinations, and 14
      zygotic combinations were identified. Four new BSs were described: ten B12, ten
      F4, ten F5, and ten G4, which are distinguished by simple paracentric inversions
      from those already known for the species. The chromosomal polymorphism belongs to
      the inversion type; its level in the Saratov population is generally the same as
      in populations of other parts of the habitat. The number of heterozygous
      inversions per specimen was 1.3; the number of heterozygous inversions per arm
      was 0.86; the percentage of heterozygous larvae was 84.5. The polymorphic arms in
      C. tentans were A, B, C, and F. Nine previously known BS were revealed in the
      karyotype of C. tentans from Central Caucasus, and no new sequences were found.
      Arm B in C. tentans was polymorphic. The zygotic combinations in all the studied
      populations were distinct.

PMID- 25857191
TI  - [A study on the taxonomy of soil amoebas from Caspian plague foci based on an
      analysis of ribosomal operon sequences].
AB  - The results of a study on the taxonomy and quantitative abundance of free-living
      amoebas in soil samples from the Russian plague foci of the northwestern Caspian
      steppe, the Caspian sand, and the Volga-Ural steppe are presented. Amoebas of the
      Willaertia and Hartmanella genera, as well as representatives of myxomycetes,
      were isolated from samples. From these, amoebas of the Acanthamoeba genus
      predominated and could be as abundantas 300000 cells per 1 g of soil. Sequencing
      of the 18S rRNA gene region showed that Acanthamoeba from the Volga-Ural steppe
      focus belonged to the A. castellanii species. Phylogenetic analysis confirmed
      that amoebas from two other Caspian foci belonged to the species of Acanthamoeba
      spp.

PMID- 25857192
TI  - Further resolving the phylogeny of Myxogastria (slime molds) based on COI and SSU
      rRNA genes.
AB  - To date, molecular systematics of Myxogastria has been based primarily on small
      subunit ribosomal RNA (SSU rRNA) and elongation factor 1-alpha (EF-1alpha) genes.
      To establish a natural classification system for the organisms, we examined
      phylogenetic relationships among myxogastrian species using cytochrome c oxidase
      subunit I (COL) and SSU rRNA genes. Twenty new sequences were obtained, including
      10 COI and 10 SSU rRNA sequences, were compared with sequences of related species
      from GenBank in order to construct phylogenic trees. The analysis of the two data
      sets supported the modern phylogeny of myxogastria: orders Liceida and Trichiida
      formed a sister group at the most basal clade, while orders Stemonitida and
      Physarida formed a close group, and order Echinostelida was a sister group to
      Stemonitida and Physarida. However, the partial COI sequences were too conserved
      to resolve of the branches in Stemonitida and Physarida. In addition, we also
      deemed the specific edited mRNA events of COI sequences in myxogastrian species.

PMID- 25857193
TI  - [Meristematic characteristics of tumors initiated by Agrobacterium tumefaciens in
      pea plants].
AB  - It is known that two key groups of plant hormones--auxins and cytokinins--play an
      important role in plant tumor development. The formation of Agrobacterium-induced
      tumors results from the horizontal transfer of bacterial oncogenes involved in
      the biosynthesis of these hormones in the plant genome. The role of
      transcriptional factors in plant tumor development is poorly investigated. It can
      be assumed that tumor development associated with abnormal cell proliferation can
      be controlled by the same set of transcription factors that control normal cell
      proliferation and, in particular, transcription factors that regulate meristem
      activity. In the present study, we analyzed the histological organization and
      distribution of proliferating cells in tumors induced by Agrobacterium
      tumefaciens on pea hypocotyls. In addition, the expression of a set of meristem
      specific genes with Agrobacterium tumefaciens-induced tumor development was
      analyzed. In general, our results indicate that meristematic structures are
      present in A. tumefaciens-induced tumors and that the development of such tumors
      is associated with increased expression of a key gene regulating the root apical
      meristem--the WOX5 gene.

PMID- 25857194
TI  - [Phylogeny of charrs of the genus Salvelinus based on mitochondrial DNA data].
AB  - Charrs of the genus Salvelinus (including Salvethymus) represent a monophyletic
      group of salmonid fishes that diverged from the common ancestor without
      subdivision into subgenera. The phylogenesis of the genus is characterized by
      four cycles of mitochondrial genome divergence. The first one, belonging to the
      Late Miocene--the border between Miocene and Pliocene (6 to 4 million years ago)-
      was associated with the consecutive divergence of the S. fontinalis, S.
      namaycush, S. levanidovi, and S. leucomaenis basal branches. Two divergence
      events, including separation of the ancestral lineage of western Pacific group of
      S. m. krascheninnikovi and the following segregation of the common ancestor into
      two mitochondrial phyla, happened within the period of 3 to 2 million years ago.
      The next cycle is attributed to the time interval of about 1 million years ago
      and includes the divergence of both phyla. In one phylum, a relatively quick
      isolation of Arctic and eastern Pacific phylogroups, along with the divergence of
      the latter phylogroup into S. confluentus and S. m. lordi lineages, took place.
      At the same time, the second phylum diverged into the S. m. malma and S. alpinus
      phylogenetic groups. At the final stage (Middle to Late Pleistocene),
      differentiation of the taxa within the phylogenetic groups took place.

PMID- 25857195
TI  - [Geographical structure of the sable (Martes zibellina L.) gene pool on the basis
      of microsatellite loci analysis].
AB  - The genetic structure of seven natural sable populations was investigated with
      the use of the original panel of 10 microsatellite loci. The populations were
      selected on the basis of the historical data on sable numbers fluctuations for
      the last 300 years, as well as on data on natural and artificial migrations
      affecting neighboring populations. We have demonstrated that the populations are
      in a state of genetic equilibrium for the majority of the loci. The genetic
      differences between three samplings from Central Siberia populations were
      insignificant, and the fixation index values were relatively low. At the same
      time, populations from the margins of the species habitation areal were
      characterized by the highest fixation index values. We have shown for the first
      time that populations from different regions of the sable habitation areal
      maintain their specific features despite the influence of natural and artificial
      migrations. The current study, performed with nuclear genetic markers, made it
      possible to get insight into the genetic structure of the analyzed species as a
      whole.

PMID- 25857196
TI  - [Genetic diversity of the locus COI-COII of mitochondrial DNA in honeybee
      populations (Apis mellifera L.) from the Tomsk region].
AB  - An assessment of the genetic diversity of the COI-COII mtDNA locus in honeybee
      populations from the Tomsk region was conducted. Three variants of the COI-COII
      mtDNA locus were registered: PQQ, PQQQ (typical for Middle Russian race), and Q
      (typical for southern breeds). It was established that 64% of bee colonies of the
      maternal line originate from the Middle Russian honeybee race, 28% of bee
      colonies originate from southern species, and 8% are mixed bee colonies. The
      southern parts of the region show a higher genetic diversity of honey bees as
      compared to northern regions, which are dominated by bee colonies (96%) and
      apiaries (73%) that are homogeneous for the genetic variant of locus COI-COII.
      The Tomsk region has no large areas with bee colonies maternally originating from
      the Middle Russian breed; only a few apiaries (both in the northern and southern
      areas) were revealed in which all bees originated from the Middle Russian breed.

PMID- 25857197
TI  - [Phylogenetic relationships among Asiatic salamanders of the genus Salamandrella
      based on variability of nuclear genes].
AB  - Based on sequence variation of three nuclear genome genes (BDNF, POMC, and RAG1),
      the phylogenetic relationships among Asiatic salamanders of the genus
      Salamandrella, Siberian salamander (S. keyserlingii) and Schrenk salamander (S.
      schrenkii), were examined. Both species demonstrated high levels of
      heterozygosity determined by intraspecific polymorphism. Fixed interspecific
      differences were revealed at one nucleotide position of the RAG1 gene, and thus
      the level of interspecific divergence over the three genes constituted only
      0.04%. Analysis of the RAG1 polymorphism across the whole range of S.
      keyserlingii showed that only one gene variant, encoding for modified RAG1
      recombinase, had the highest distribution to the north of the Amur region (west
      and northeast of Siberia). It is possible that the changes in the RAG1 gene in
      Siberian salamander are of an adaptive nature. However, cases of interspecific
      hybridization were identified in Jewish autonomous oblast (JAO), which contains
      one of the range borders between the two Salamandrella species.

PMID- 25857198
TI  - [CYP2D6, CYP3A5, and CYP3A4 gene polymorphism in Russian, Tatar, and Bashkir
      populations].
AB  - The allele and genotype frequency distribution at polymorphic loci rs3892097
      (184G>A) of CYP2D6 gene, rs776746 (6986A>G) of the CYP3A5 gene and rs2740574 (
      392A>G) of the CYP3A4 gene in Russians, Tatars, and Bashkirs was examined.
      Samples were taken from residents of Bashkortostan Republic (1240 men and women
      aged from 20 to 109 years and consisted of 443 Russians, 517 Tatars, and 280
      Bashkirs). Allele identification was conducted using PCR-RFLP or PCR with TaqMan
      probes. The "nonfunctional" allele rs3892097*A of the CYP2D6 gene was detected in
      populations of Russians, Tatars, and Bashkirs in 17.2, 9.5, and 7.1% cases,
      respectively. The rs776746*G allele of the CYP3A5 gene encoding the CYP3A5
      isoenzyme with decreased activity was revealed with a frequency of 94.6% in
      populations of Russians, 94.3% in the Tatar population, and 91.5% in the Bashkir
      population. The share of the minor allele rs2740574*G of the CYP3A4 was 4.0% in
      populations of Russians, 0.5% in the Tatar population, and 0.9% in the Bashkir
      population. It has been previously shown that the rs3892097*A, rs776746*G, and
      rs2740574*G allele frequencies vary significantly in different world populations.
      Since allele variants of CYP2D6, CYP3A5, and CYP3A4 genes can play essential role
      in interindividual and in interethnic differences in the metabolism of many
      therapeutic agents, the obtained results could be used in the prognosis of
      pharmacotherapy efficacy in populations of Russians, Tatars, and Bashkirs.

PMID- 25857199
TI  - [Genetic characterization of populations of the Volga-Ural region according to
      the variability of the Y-chromosome].
AB  - An analysis of genetic diversity in nine ethnic groups of the Volga-Ural region
      was carried out using 15 biallelic loci in the nonrecombining region of the Y
      chromosome. The major Y-chromosome haplogroups in the region are R1a-M198, R1b
      M269, and N-M231. It was found that Bashkirs show the greatest difference from
      other populations of the Volga-Ural region according both to F(st) and to the
      principal component analysis. In addition, analysis of the frequency distribution
      of Y-chromosome haplogroups was carried out in the Besermyan population, which
      was not studied previously from the Y-chromosome perspective. The results of this
      study revealed the predominance of haplogroup N-M231 (54.7%) in this ethnic
      group, which may indicate the prevalence of the Finno-Ugric component in the
      formation of the patrilineal component in the gene pool of the Besermyan ethnic
      group.

PMID- 25857200
TI  - Development of polymorphic microsatellites for Meloidogyne incognita, through
      screening predicted microsatellite loci based on genome sequence.
AB  - Microsatellites are extensively distributed in the eukaryotic genome, and they
      are widely used for their high polymorphism and accessibility. The
      microsatellites in M. incognita, a worldwide agriculture pest, are inadequate for
      diversity research. A repertoire of 1620 microsatellites appeared appropriate to
      design primer as markers were identified based on the M. incognita genome. 120
      loci were chosen as candidate, from which 88 microsatellites were characterized.
      Finally, we found 13 polymorphic microsatellites with 2 to 23 alleles in a survey
      of three nematode populations in China, while other positive loci were
      monomorphic. These new molecular markers afford to genetic diversity analysis in
      M. incognita population of poorly investigation. Furthermore, the predicted
      microsatellites have potential values for other plant parasitic nematodes.

PMID- 25857201
TI  - Two in vitro methods for screening potential parasiticides against
      Ichthyophthirius multifiliis using Tetrahymena thermophila.
AB  - Ichthyophthirius multifiliis (Ich) is a ciliate parasite that infects many
      species of freshwater fishes worldwide and causes heavy economic losses in
      aquaculture. Currently, parasiticides for controlling this parasite are limited,
      and few pond-practical chemical therapies exist. Hence, the search for new
      parasiticides is urgently needed. One challenge confronting the screening of
      potential parasiticides is the difficulty in raising enough parasite for efficacy
      testing as Ich is an obligate parasite. This study used species of Tetrahymena,
      Ich-related and cultivable ciliate protozoa, to evaluate two in vitro methods to
      test parasiticides. Plate counting and MTS assays (CellTiter 96(r) AQueous Non
      Radioactive Cell Proliferation Assay) were used to compare lethal concentrations
      or median lethal concentrations (LC50) of copper sulphate, formalin and malachite
      green between T. thermophila and Ich theronts or between T. thermophila and Ich
      tomonts. The parasiticides that killed T. thermophila have been demonstrated to
      kill theronts or tomonts. These in vitro methods using T. thermophila can be used
      to screen novel parasiticides against Ich.

PMID- 25857202
TI  - Transthyretin Asp38Tyr: a new mutation associated to a late onset neuropathy.

PMID- 25857204
TI  - What to consider when regulating electronic cigarettes: Pros, cons and unintended
      consequences.
AB  - Many public health experts, medical research societies, large health
      organizations and policy makers have expressed concerns about the increased
      popularity of electronic cigarettes and have pushed for more restrictive measures
      ranging from complete bans to tight regulations of these products either as
      medicines or as tobacco products. But these concerns have never been adequately
      qualified nor quantified. Without judicious assessment and thorough evaluation,
      regulations may have unintended consequences that can do more damage than good in
      public health terms. In this article, we will appraise the existing prominent
      regulatory frameworks for e-cigarettes, namely, general consumer product,
      medicinal product and tobacco product regulation, to highlight their pros and
      cons. Moreover, we provide concrete examples of the unintended consequences which
      may arise from inappropriate regulatory action. 

PMID- 25857203
TI  - Altered IgG autoantibody levels and CD4(+) T cell subsets in lupus-prone Nba2
      mice lacking the nuclear progesterone receptor.
AB  - Important interactions between female reproduction and autoimmunity are suggested
      by the female-predominance of systemic lupus erythematosus (SLE) and other
      autoimmune diseases and the amelioration of certain autoimmune diseases during
      pregnancy. Sexually dimorphic risk of developing SLE involves modulation of
      genetic risk by environmental factors, sex hormones and non-hormonal factors
      encoded on the sex chromosomes. In some lupus models, estrogen, via estrogen
      receptor alpha (ER-alpha), enhances production of highly pathogenic IgG2a/c
      autoantibodies (autoAbs). Some studies indicate that treatment with progesterone,
      a chief female reproductive steroid, can suppress IgG2a/2c autoAb production.
      Little is known about how endogenous progesterone impacts lupus autoimmunity. To
      investigate this, we introduced a disruptive progesterone receptor (PR) gene
      mutation into lupus-prone mice and tracked the development of spontaneous IgG
      autoAbs. Here, we present evidence that PR can suppress the emergence of class
      switched IgG2c autoAbs, suggesting that PR and ER-alpha counter-regulate a
      critical step in lupus autoimmunity. PR's control of IgG2c autoAb production
      correlates with alterations in the relative abundance of splenic T follicular
      helper (TFH) cells and non-TFH CD4(+) T cells, especially regulatory T cells
      (TREGS). Surprisingly, PR also appears to help to maintain sexually dimorphic
      abundance of splenic leukocytes, a feature common to many mouse models of SLE.
      Together our results identify a novel molecular link between female reproduction
      and lupus autoimmunity. Further investigation into the immunomodulatory functions
      of PR promises to inform reproductive health care in women and offers mechanistic
      insight into important immunologic phenomena of pregnancy. 

PMID- 25857205
TI  - Factors influencing breastfeeding exclusivity during the first 6 months of life
      in developing countries: a quantitative and qualitative systematic review.
AB  - Breastfeeding is the most advantageous feeding option for infants, and
      epidemiological studies provide evidence for its promotion. The objective of this
      review was to comprehensively delineate the barriers and facilitators of
      exclusive breastfeeding of infants aged 0-6 months old by mothers in developing
      countries. A search of CINAHL, MEDLINE and PsycINFO was carried out to retrieve
      studies from January 2001 to January 2014. Using our inclusion criteria, we
      selected studies that described barriers and facilitators of exclusive
      breastfeeding. Qualitative and quantitative studies were considered. Twenty-five
      studies involving 11 025 participants from 19 countries were included. Barriers
      and facilitators of exclusive/full breastfeeding were identified, analysed
      tabulated and summarised in this review. Maternal employment was the most
      frequently cited barrier to exclusive breastfeeding. Maternal perceptions of
      insufficient breast milk supply was pervasive among studies while medical
      barriers related to illness of mothers and/or infants as well as breast problems,
      rather than health care providers. Socio-cultural factors such as maternal and
      significant other's beliefs about infant nutrition also often constitute strong
      barriers to exclusive breastfeeding. Despite these barriers, mothers in
      developing countries often possess certain personal characteristics and develop
      strategic plans to enhance their success at breastfeeding. Health care providers
      should be informed about the determinants of exclusive breastfeeding and provide
      practical anticipatory guidance targeted at overcoming these barriers. In so
      doing, health care providers in developing countries can contribute to improving
      maternal and child health outcomes. 

PMID- 25857207
TI  - Fast graphically inspired algorithm for assignment of molecular formulae in
      ultrahigh resolution mass spectrometry.
AB  - This study focuses on the deterministic task of assigning molecular formulae to
      exact masses that are generated by ultrahigh resolution mass spectrometry. A new
      algorithm based on low-mass moieties (LMMs) such as CH4O(-1) and C4O(-3)
      completely replaces conventional computational loops that explore a user-defined
      range of C, H, and O when searching for molecular formulae that have a given
      exact mass. The LMM-based algorithm has been coupled with a combinatorial
      algorithm that uses nested loops for N, P, S, and (13)C to assign molecular
      formulae. The resulting program is more than 1700 times faster than its brute
      force counterpart that uses nested loops for all elements, and both programs
      yield identical output files. The new LMM-based program is 1050 times faster than
      the open-source program HR2, 60 times faster than Molecular Formula Calculator,
      and 3.6 times faster than MassCalc/FormCalc.

PMID- 25857206
TI  - Pontin functions as an essential coactivator for Oct4-dependent lincRNA
      expression in mouse embryonic stem cells.
AB  - The actions of transcription factors, chromatin modifiers and noncoding RNAs are
      crucial for the programming of cell states. Although the importance of various
      epigenetic machineries for controlling pluripotency of embryonic stem (ES) cells
      has been previously studied, how chromatin modifiers cooperate with specific
      transcription factors still remains largely elusive. Here, we find that Pontin
      chromatin remodelling factor plays an essential role as a coactivator for Oct4
      for maintenance of pluripotency in mouse ES cells. Genome-wide analyses reveal
      that Pontin and Oct4 share a substantial set of target genes involved in ES cell
      maintenance. Intriguingly, we find that the Oct4-dependent coactivator function
      of Pontin extends to the transcription of large intergenic noncoding RNAs
      (lincRNAs) and in particular linc1253, a lineage programme repressing lincRNA, is
      a Pontin-dependent Oct4 target lincRNA. Together, our findings demonstrate that
      the Oct4-Pontin module plays critical roles in the regulation of genes involved
      in ES cell fate determination. 

PMID- 25857208
TI  - Reply to: Hemodynamic and Arterial Stiffness Parameters in Ambulatory Blood
      Pressure Phenotypes and the Clinical Scenario of Polypharmacy and Comorbidities.

PMID- 25857209
TI  - Role of granulocyte transfusions in invasive fusariosis: systematic review and
      single-center experience.
AB  - BACKGROUND: Invasive Fusarium infection is relatively refractory to available
      antifungal agents. Invasive fusariosis (IF) occurs almost exclusively in the
      setting of profound neutropenia and/or systemic corticosteroid use. Treatment
      guidelines for IF are not well established, including the role of granulocyte
      transfusions (GTs) to counter neutropenia. STUDY DESIGN AND METHODS: We conducted
      a systematic review, identifying IF cases where GTs were used as adjunctive
      therapy to antifungal agents and also report a single-center case series
      detailing our experience (1996-2012) of all IF cases treated with antifungal
      agents and GTs. In the systematic review cases, GTs were predominantly collected
      from nonstimulated donors whereas, in the case series, they were universally
      derived from dexamethasone- and granulocyte-colony-stimulating factor-stimulated
      donors. RESULTS: Twenty-three patients met inclusion criteria for the systematic
      review and 11 for the case series. Response rates after GTs were 30 and 91% in
      the review and case series, respectively. Survival to hospital discharge remained
      low at 30 and 45%, respectively. Ten patients in the systematic review and three
      in the case series failed to achieve hematopoietic recovery and none of these
      survived. In the case series, donor-stimulated GTs generated mean "same-day"
      neutrophil increments of 3.35 * 10(9)  +/- 1.24 * 10(9) /L and mean overall
      posttransfusion neutrophil increments of 2.46 * 10(9)  +/- 0.85 * 10(9) /L.
      Progressive decrements in neutrophil response to GTs in two cases were attributed
      to GT-related HLA alloimmunization. CONCLUSION: In patients with IF, donor
      stimulated GTs may contribute to high response rates by effectively bridging
      periods of neutropenia or marrow suppression. However, their utility in the
      absence of neutrophil recovery remains questionable.

PMID- 25857210
TI  - Virus-induced preferential antibody gene-usage and its importance in humoral
      autoimmunity.
AB  - It is known that even the adaptive components of the immune system are based on
      genetic traits common to all individuals, and that diversity is shaped by the
      lifelong contacts with different non-self antigens, including those found on
      infectious pathogens. Besides the individual differences, some of these common
      traits may be more prone to react against a given antigen, and this may be
      exploited by the infectious pathogens. Indeed, viral infections can deregulate
      immune response by subverting antibody (Ab) gene usage, leading to the
      overexpression of specific Ab subfamilies. This overexpression often results in a
      protective antiviral response but, in some cases, also correlates with a higher
      likelihood of developing humoral autoimmune disorders. These aspects of virus
      induced autoimmunity have never been thoroughly reviewed, and this is the main
      purpose of this review. An accurate examination of virus specific Ab subfamilies
      elicited during infections may help further characterize the complex interplay
      between viruses and the humoral immune response, and be useful in the design of
      future monoclonal antibody (mAb)-based anti-infective prophylactic and
      therapeutic strategies. 

PMID- 25857212
TI  - Exploring personality dimensions that influence practice and performance of a
      simulated laparoscopic task in the objective structured clinical examination.
AB  - BACKGROUND: Surgical educators have encouraged the investigation of individual
      differences in aptitude and personality in surgical performance. An individual
      personality difference that has been shown to influence laparoscopic performance
      under time pressure is movement specific reinvestment. Movement specific
      reinvestment has 2 dimensions, movement self-consciousness (MS-C) (i.e., the
      propensity to consciously monitor movements) and conscious motor processing (CMP)
      (i.e., the propensity to consciously control movements), which have been shown to
      differentially influence laparoscopic performance in practice but have yet to be
      investigated in the context of psychological stress (e.g., the objective
      structured clinical examination [OSCE]). OBJECTIVE: This study investigated the
      role of individual differences in propensity for MS-C and CMP in practice of a
      fundamental laparoscopic skill and in laparoscopic performance during the OSCE.
      Furthermore, this study examined whether individual differences during practice
      of a fundamental laparoscopic skill were predictive of laparoscopic performance
      during the OSCE. METHODS: Overall, 77 final-year undergraduate medical students
      completed the movement specific reinvestment scale, an assessment tool that
      quantifies the propensity for MS-C and CMP. Participants were trained to
      proficiency on a fundamental laparoscopic skill. The number of trials to reach
      proficiency was measured, and completion times were recorded during early
      practice, later practice, and the OSCE. RESULTS: There was a trend for CMP to be
      negatively associated with the number of trials to reach proficiency (p = 0.064).
      A higher propensity for CMP was associated with fewer trials to reach proficiency
      (beta = -0.70, p = 0.023). CMP and MS-C did not significantly predict completion
      times in the OSCE (p > 0.05). Completion times in early practice (beta = 0.05, p
      = 0.016) and later practice (beta = 0.47, p < 0.001) and number of trials to
      reach proficiency (beta = 0.23, p = 0.003) significantly predicted completion
      times in the OSCE. CONCLUSION: It appears that a higher propensity for CMP
      predicts faster rates of learning of a fundamental laparoscopic skill.
      Furthermore, laparoscopic performance during practice is indicative of
      laparoscopic performance in the challenging conditions of the OSCE. The lack of
      association between the 2 dimensions of movement specific reinvestment and
      performance during the OSCE is explained using the theory of reinvestment as a
      framework. Overall, consideration of personality differences and individual
      differences in ability during practice could help inform the development of
      individualized surgical training programs.

PMID- 25857213
TI  - Identifying gaps in the surgical training curriculum in Rwanda through evaluation
      of operative activity at a teaching hospital.
AB  - OBJECTIVE: To define the operations performed by surgical residents at a tertiary
      referral hospital in Rwanda to help guide development of the residency program.
      DESIGN: Cross-sectional study of all patients operated by surgical residents from
      October 2012 to September 2013. SETTING: University Teaching Hospital of Kigali
      (Centre Hospitalier Universitaire de Kigali [CHUK]), a public, tertiary referral
      hospital in Kigali, Rwanda. PARTICIPANTS: All patient data were entered into the
      operative database by surgical residents at CHUK. A total of 2833 cases were
      entered into the surgical database. Of them, 53 cases were excluded from further
      analysis because no surgical resident was listed as the primary or assistant
      surgeon, leaving 2780 cases for analysis. RESULTS: There were 2780 operations
      involving surgical residents. Of them, 51% of procedures were classified under
      general surgery, 38% orthopedics, 7% neurosurgery, and 4% urology. Emergency
      operations accounted for 64% of the procedures, with 56% of those being general
      surgery and 35% orthopedic. Further, 50% of all operations were trauma, with 71%
      of those orthopedic and 21% general surgery. Surgical faculty were involved in
      45% of operations as either the primary or the assistant surgeons, while the
      remainder of operations did not involve surgical faculty. Residents were primary
      surgeons in 68% of procedures and assistant surgeons in 84% of procedures.
      CONCLUSIONS: The operative experience of surgery residents at CHUK primarily
      involves emergency and trauma procedures. Although this likely reflects the
      demographics of surgical care within Rwanda, more focus should be placed on
      elective procedures to ensure that surgical residents are broadly trained.

PMID- 25857214
TI  - Nanoscale pillar arrays for separations.
AB  - The work presented herein evaluates silicon nano-pillar arrays for use in planar
      chromatography. Electron beam lithography and metal thermal dewetting protocols
      were used to create nano-thin layer chromatography platforms. With these
      fabrication methods we are able to reduce the size of the characteristic features
      in a separation medium below that used in ultra-thin layer chromatography; i.e.
      pillar heights are 1-2 MUm and pillar diameters are typically in the 200-400 nm
      range. In addition to the intrinsic nanoscale aspects of the systems, it is shown
      they can be further functionalized with nanoporous layers and traditional
      stationary phases for chromatography; hence exhibit broad-ranging lab-on-a-chip
      and point-of-care potential. Because of an inherent high permeability and very
      small effective mass transfer distance between pillars, chromatographic
      efficiency can be very high but is enhanced herein by stacking during development
      and focusing while drying, yielding plate heights in the nm range separated band
      volumes. Practical separations of fluorescent dyes, fluorescently derivatized
      amines, and anti-tumor drugs are illustrated. 

PMID- 25857211
TI  - The resolution code of acute inflammation: Novel pro-resolving lipid mediators in
      resolution.
AB  - Studies into the mechanisms in resolution of self-limited inflammation and acute
      reperfusion injury have uncovered a new genus of pro-resolving lipid mediators
      coined specialized pro-resolving mediators (SPM) including lipoxins, resolvins,
      protectins and maresins that are each temporally produced by resolving-exudates
      with distinct actions for return to homeostasis. SPM evoke potent anti
      inflammatory and novel pro-resolving mechanisms as well as enhance microbial
      clearance. While born in inflammation-resolution, SPM are conserved structures
      with functions discovered in microbial defense, pain, organ protection and tissue
      regeneration, wound healing, cancer, reproduction, and neurobiology-cognition.
      This review covers these SPM mechanisms and other new omega-3 PUFA pathways that
      open their path for functions in resolution physiology. 

PMID- 25857215
TI  - Identification of phenolics in litchi and evaluation of anticancer cell
      proliferation activity and intracellular antioxidant activity.
AB  - Litchi leaf is a good resource for phenolics, which are good candidates for
      medicines. In this work, three phenolics were isolated from litchi leaf by column
      chromatography. Their structures were identified by electrospray ionization-mass
      spectrometry (ESI-MS) and nuclear magnetic resonance (NMR) spectroscopy as
      secoisolariciresinol 9'-O-beta-D-xyloside (1), 4,7,7',8',9,9'-hexahydroxy-3,3'
      dimethoxy-8,4'-oxyneolignan (2), and cinnamtannin B1 (3). Cinnamtannin B1 showed
      better extra- and intracellular antioxidant activities than Compounds 1 and 2.
      The intracellular antioxidant activity of cinnamtannin B1 was related to the
      upregulation of endogenous antioxidant enzyme activities (superoxide dismutase,
      catalase, and glutathione peroxidase), and inhibition of ROS generation.
      Furthermore, cinnamtannin B1 exhibited strong antiproliferative effects against
      HepG2 and Siha cell lines with no significant cytotoxicities. In the case of the
      HepG2 cell line, cell cycle arrest and apoptosis induction were the underlying
      anticancer mechanisms of cinnamtannin B1. The results indicated that cinnamtannin
      B1 was a potent cancer cell proliferation inhibitor and a good intracellular
      antioxidant. 

PMID- 25857216
TI  - Role of labile iron in the toxicity of pharmacological ascorbate.
AB  - Pharmacological ascorbate has been shown to induce toxicity in a wide range of
      cancer cell lines. Pharmacological ascorbate in animal models has shown promise
      for use in cancer treatment. At pharmacological concentrations the oxidation of
      ascorbate produces a high flux of H2O2 via the formation of ascorbate radical
      (Asc(*-)). The rate of oxidation of ascorbate is principally a function of the
      level of catalytically active metals. Iron in cell culture media contributes
      significantly to the rate of H2O2 generation. We hypothesized that increasing
      intracellular iron would enhance ascorbate-induced cytotoxicity and that iron
      chelators could modulate the catalytic efficiency with respect to ascorbate
      oxidation. Treatment of cells with the iron-chelators deferoxamine (DFO) or
      dipyridyl (DPD) in the presence of 2mM ascorbate decreased the flux of H2O2
      generated by pharmacological ascorbate and reversed ascorbate-induced toxicity.
      Conversely, increasing the level of intracellular iron by preincubating cells
      with Fe-hydroxyquinoline (HQ) increased ascorbate toxicity and decreased
      clonogenic survival. These findings indicate that redox metal metals, e.g.,
      Fe(3+)/Fe(2+), have an important role in ascorbate-induced cytotoxicity.
      Approaches that increase catalytic iron could potentially enhance the
      cytotoxicity of pharmacological ascorbate in vivo. 

PMID- 25857217
TI  - Impact on costs of switching one-ray aponeurectomy to percutaneous needle
      aponeurotomy in Dupuytren's disease: A model analysis.
AB  - OBJECTIVE: To assess the cost of switching surgical aponeurectomy to percutaneous
      needle aponeurotomy in one-ray Dupuytren's disease. METHODS: A model analysis was
      performed with a cross-sectional national survey of public and private French
      hospitals in 2012. All stays for one-ray aponeurectomy were "virtually" replaced
      with 1, 2 or 3 outpatient sessions of percutaneous needle aponeurotomy. The costs
      were based on the hospital cost (tariff per disease-related group) and on common
      classification of medical procedures performed in outpatient care for 2013.
      RESULTS: Dupuytren's disease represented 18,707 hospitalizations (?26 million
      [2013 euros]) in France in 2012, 8534 hospitalizations for one-ray aponeurectomy
      (?11.9 million). By replacing surgical aponeurectomy with percutaneous needle
      aponeurotomy for one-ray Dupuytren's disease, 91% to 97% and 56% to 59% of the
      treatment costs could be saved using hospitalizations for one-ray aponeurectomy
      or total hospital costs, respectively, as reference. CONCLUSIONS: Replacing
      aponeurectomy with percutaneous needle aponeurotomy for one-ray Dupuytren's
      disease could greatly reduce the treatment costs for all Dupuytren's disease.
      Effective alternatives to surgery for Dupuytren's disease, such as needle
      aponeurotomy in an outpatient setting should be considered in the economic
      perspective.

PMID- 25857218
TI  - Acute phase proteins in racehorses with inflammatory airway disease.
AB  - BACKGROUND: Systemic inflammation is observed in horses with heaves and could
      also be present in horses with a lesser degree of pulmonary inflammation.
      HYPOTHESIS/OBJECTIVES: It was hypothesized that racehorses with inflammatory
      airway disease (IAD) have increased concentration of circulating acute phase
      proteins. The objective of this study was to compare serum acute phase proteins
      of racehorses with and without lower airway inflammation. ANIMALS: Serum from 21
      client-owned Standardbred racehorses with exercise intolerance and lower airway
      inflammation and serum from 10 client-owned Standardbred racehorses with exercise
      intolerance without lower airway inflammation. METHODS: In a case-control study,
      serum samples from previously characterized horses presented for exercise
      intolerance with or without lower airway inflammation based on bronchoalveolar
      lavage fluid cytology were analyzed for serum amyloid A protein (SAA), C-reactive
      protein (CRP), and haptoglobin using commercial ELISAs. RESULTS: There was no
      significant differences between groups for SAA (non-IAD versus IAD, median
      (range): 3.47 (0.06-34.94) versus 6.33 (0.06-80) MUg/mL, P = .49), CRP (10.87
      (2.05-29.03) versus 4.63 (0.02-31.81) MUg/mL, P = .23) or haptoglobin (900.36
      (607.99-2018.84) versus 749.54 (530.81-1076.95) MUg/mL, P = .09). CONCLUSIONS AND
      CLINICAL IMPORTANCE: In this population of poorly performing racehorses in
      training, serum SAA, CRP, and haptoglobin were not helpful in distinguishing
      between horses with IAD from horses with exercise intolerance from other causes.

PMID- 25857220
TI  - HITCal: a software tool for analysis of video head impulse test responses.
AB  - CONCLUSION: The developed software (HITCal) may be a useful tool in the analysis
      and measurement of the saccadic video head impulse test (vHIT) responses and with
      the experience obtained during its use the authors suggest that HITCal is an
      excellent method for enhanced exploration of vHIT outputs. OBJECTIVE: To develop
      a (software) method to analyze and explore the vHIT responses, mainly saccades.
      METHODS: HITCal was written using a computational development program; the
      function to access a vHIT file was programmed; extended head impulse exploration
      and measurement tools were created and an automated saccade analysis was
      developed using an experimental algorithm. For pre-release HITCal laboratory
      tests, a database of head impulse tests (HITs) was created with the data
      collected retrospectively in three reference centers. This HITs database was
      evaluated by humans and was also computed with HITCal. RESULTS: The authors have
      successfully built HITCal and it has been released as open source software; the
      developed software was fully operative and all the proposed characteristics were
      incorporated in the released version. The automated saccades algorithm
      implemented in HITCal has good concordance with the assessment by human observers
      (Cohen's kappa coefficient = 0.7).

PMID- 25857219
TI  - Synthesis and pharmacological evaluation of M4 muscarinic receptor positive
      allosteric modulators derived from VU10004.
AB  - The M4 mAChR is implicated in several CNS disorders and possesses an allosteric
      binding site for which ligands modulating the affinity and/or efficacy of ACh may
      be exploited for selective receptor targeting. We report the synthesis of a
      focused library of putative M4 PAMs derived from VU10004. These compounds
      investigate the pharmacological effects of target thieno[2,3-b]pyridines
      assembled from primary cycloalkanamines and cyclic secondary amines providing
      useful estimates of affinity (KB), cooperativity (alphabeta), and direct agonist
      properties (tauB). 

PMID- 25857221
TI  - Patients' experiences and providers' observations on pain during intrauterine
      device insertion.
AB  - OBJECTIVE: To determine women's (patients') experiences of intrauterine device
      (IUD) insertion under our current practice and the extent to which these agreed
      with the observations of the health professionals (providers) who had performed
      the IUD insertion procedures. METHOD: Questionnaires were used to collect
      information on women's experiences of the IUD insertion procedure from both
      patients and providers in a sexual and reproductive health service. RESULTS:
      Overall response rates were high (77%, 284 responses in total). Seventy-three
      percent of patients were nulliparous and over half nulligravid. The providers
      predominantly used local anaesthesia for IUD insertions (93%). Most patients
      reported being anxious before their procedure (86%). Patients mainly described
      the overall experience of their IUD insertion procedure as being associated with
      'minimal discomfort/nothing' (42%) or 'uncomfortable' (41%). 'Minimal
      discomfort/nothing' (56%) and 'uncomfortable' (33%) were the main observations of
      providers. When responses of patients and their providers were compared,
      agreement was slight for reported pain levels (k = 0.167 CI [0.13-0.24]).
      Patients' reported pain levels were significantly higher than those reported to
      have been observed by their providers (p < 0.001). CONCLUSION: Patients' and
      providers' responses suggested that the IUD insertion procedure under our current
      practice appeared acceptable to most patients. However, providers were not
      usually accurate in their observations and tended to underestimate the degree of
      pain experienced by their patients during IUD insertion procedures.

PMID- 25857222
TI  - Rare taxa have potential to make metabolic contributions in enhanced biological
      phosphorus removal ecosystems.
AB  - Enhanced biological phosphorus removal (EBPR) relies on diverse but specialized
      microbial communities to mediate the cycling and ultimate removal of phosphorus
      from municipal wastewaters. However, little is known about microbial activity and
      dynamics in relation to process fluctuations in EBPR ecosystems. Here, we
      monitored temporal changes in microbial community structure and potential
      activity across each bioreactor zone in a pilot-scale EBPR treatment plant by
      examining the ratio of small subunit ribosomal RNA (SSU rRNA) to SSU rRNA gene
      (rDNA) over a 120 day study period. Although the majority of operational
      taxonomic units (OTUs) in the EBPR ecosystem were rare, many maintained high
      potential activities based on SSU rRNA : rDNA ratios, suggesting that rare OTUs
      contribute substantially to protein synthesis potential in EBPR ecosystems. Few
      significant differences in OTU abundance and activity were observed between
      bioreactor redox zones, although differences in temporal activity were observed
      among phylogenetically cohesive OTUs. Moreover, observed temporal activity
      patterns could not be explained by measured process parameters, suggesting that
      other ecological drivers, such as grazing or viral lysis, modulated community
      interactions. Taken together, these results point towards complex interactions
      selected for within the EBPR ecosystem and highlight a previously unrecognized
      functional potential among low abundance microorganisms in engineered ecosystems.

PMID- 25857224
TI  - Platelet transfusion reverses bleeding evoked by triple anti-platelet therapy
      including vorapaxar, a novel platelet thrombin receptor antagonist.
AB  - Vorapaxar is a novel protease-activated receptor-1 (PAR-1) antagonist recently
      approved for the reduction of thrombotic cardiovascular events in patients with a
      history of myocardial infarction or with peripheral arterial disease. Patients
      who received vorapaxar in addition to standard of care antiplatelet therapy had
      an increased incidence of major bleeding events compared with placebo. To assess
      whether platelet transfusion can restore hemostasis in primates on triple
      antiplatelet therapy, template bleeding times were assessed concurrently in the
      buccal mucosa, finger pad, and distolateral tail of anesthetized cynomolgus
      macaques to evaluate bleeding with vorapaxar as either monotherapy or in
      combination with aspirin or aspirin and clopidogrel. Aspirin (5mg/kg, IV) or
      vorapaxar (1mg/kg, PO) alone had no significant effect on bleeding times in the
      three vascular beds examined. A modest (<2-fold) increase in bleeding time was
      achieved in the three beds with the dual combination of aspirin and vorapaxar.
      Major increases in bleeding time were achieved in the three beds with the triple
      combination of aspirin (5mg/kg, IV), vorapaxar (1mg/kg, PO), and clopidogrel
      (1mg/kg, PO). Transfusion of fresh human platelet rich plasma, but not platelet
      poor plasma, reversed the increase in bleeding time in the triple therapy group.
      Transfusion of human platelets may be a viable approach in situations requiring a
      rapid reversal of platelet function in individuals treated with triple anti
      platelet therapy that includes vorapaxar. 

PMID- 25857223
TI  - Reversal strategies for vitamin K antagonists in acute intracerebral hemorrhage.
AB  - OBJECTIVE: There is little evidence to guide treatment strategies for
      intracerebral hemorrhage on vitamin K antagonists (VKA-ICH). Treatments utilized
      in clinical practice include fresh frozen plasma (FFP) and prothrombin complex
      concentrate (PCC). Our aim was to compare case fatality with different reversal
      strategies. METHODS: We pooled individual ICH patient data from 16 stroke
      registries in 9 countries (n = 10 282), of whom 1,797 (17%) were on VKA. After
      excluding 250 patients with international normalized ratio < 1.3 and/or missing
      data required for analysis, we compared all-cause 30-day case fatality using Cox
      regression. RESULTS: We included 1,547 patients treated with FFP (n = 377, 24%),
      PCC (n = 585, 38%), both (n = 131, 9%), or neither (n = 454, 29%). The crude case
      fatality and adjusted hazard ratio (HR) were highest with no reversal (61.7%, HR
      = 2.540, 95% confidence interval [CI] = 1.784-3.616, p < 0.001), followed by FFP
      alone (45.6%, HR = 1.344, 95% CI = 0.934-1.934, p = 0.112), then PCC alone
      (37.3%, HR = 1.445, 95% CI = 1.014-2.058, p = 0.041), compared to reversal with
      both FFP and PCC (27.8%, reference). Outcomes with PCC versus FFP were similar
      (HR = 1.075, 95% CI = 0.874-1.323, p = 0.492); 4-factor PCC (n = 441) was
      associated with higher case fatality compared to 3-factor PCC (n = 144, HR =
      1.441, 95% CI = 1.041-1.995, p = 0.027). INTERPRETATION: The combination of FFP
      and PCC might be associated with the lowest case fatality in reversal of VKA-ICH,
      and FFP may be equivalent to PCC. Randomized controlled trials with functional
      outcomes are needed to establish the most effective treatment.

PMID- 25857225
TI  - JTP-103237, a novel monoacylglycerol acyltransferase inhibitor, modulates fat
      absorption and prevents diet-induced obesity.
AB  - Monoacylglycerol acyltransferase 2 (MGAT2) plays an important role in intestinal
      fat absorption. We discovered the novel MGAT2 inhibitor, JTP-103237, and
      evaluated its pharmacological profile. JTP-103237 selectively inhibited MGAT2
      without remarkable species differences and reduced absorbed lipids in
      circulation. After lipid administration, JTP-103237 slightly but significantly
      decreased triglyceride content in proximal small intestine and significantly
      increased the lipids content in the distal small intestine. In addition, JTP
      103237 significantly increased MGAT substrate (monoacylglycerol and fatty acid)
      content in the small intestine. JTP-103237 increased plasma peptide YY levels
      after lipid loading and reduced food intake in a dietary fat-dependent manner.
      After chronic treatment, JTP-103237 significantly decreased body weight and
      increased O2 consumption in the early dark phase in high fat diet induced obese
      (DIO) mice. Moreover, JTP-103237 improved glucose tolerance and decreased fat
      weight and hepatic triglyceride content in DIO mice. Our findings indicate that
      JTP-103237 prevents diet-induced obesity by inhibiting intestinal MGAT2 and has
      unique properties as a drug for the treatment of obesity. 

PMID- 25857226
TI  - CHOP mediates XBP1S-induced renal mesangial cell necrosis following high glucose
      treatment.
AB  - High glucose (HG)-induced apoptosis in mesangial cells (MCs) is a critical
      determinant during the pathogenesis of diabetic nephropathy. The signaling
      cascade inducing MCs apoptosis by HG involves overproduction of reactive oxygen
      species. Our previous studies have demonstrated that HG-induced oxidative stress
      is mediated by suppression of spliced/active X-box binding protein 1 (XBP1S),
      suggesting the importance of XBP1S in HG-induced MCs apoptosis. CHOP, an
      endoplasmic reticulum stress-associated proapoptotic signal, is involved in
      downstream of XBP1S. In the present study, we explored the effect of XBP1S in
      modulating HG-induced apoptosis in renal MCs and then identified the role of CHOP
      in these processes. Apoptosis and necrosis were quantified by flow cytometry;
      protein levels of XBP1S, caspase3, Bax, Bcl2, BNIP3, and CHOP were analyzed by
      Western blotting. The cellular localization of XBP1S was determined by
      immunofluorescence histochemistry. The binding of XBP1 to CHOP promoter was
      determined by chromatin immunoprecipitation assays. In addition, adenoviruses
      harboring XBP1S gene (Ad-XBP1S) were used to overexpress XBP1S, whereas the
      knockdown of CHOP was achieved by small interference RNA. HG suppressed nuclear
      distribution of XBP1S and induced apoptosis and necrosis in MCs. Ad-XBP1S
      infection enhanced the nuclear translocation of XBP1S and reduced MCs apoptosis
      and necrosis. XBP1S bound to the promoter region of CHOP and upregulated CHOP
      expression. Conversely, CHOP expression was reduced upon HG exposure and
      knockdown of CHOP increased necrosis but not apoptosis in MCs. These results
      suggest that XBP1S protected MCs from HG-induced apoptosis and necrosis, and CHOP
      participates in XBP1S-regulated necrosis but not apoptosis. 

PMID- 25857227
TI  - Deletion of ocular transforming growth factor beta signaling mimics essential
      characteristics of diabetic retinopathy.
AB  - Diabetic retinopathy, a major cause of blindness, is characterized by a distinct
      phenotype. The molecular causes of the phenotype are not sufficiently clear.
      Here, we report that deletion of transforming growth factor beta signaling in the
      retinal microenvironment of newborn mice induces changes that largely mimic the
      phenotype of nonproliferative and proliferative diabetic retinopathy in humans.
      Lack of transforming growth factor beta signaling leads to the formation of
      abundant microaneurysms, leaky capillaries, and retinal hemorrhages. Retinal
      capillaries are not covered by differentiated pericytes, but by a coat of
      vascular smooth muscle-like cells and a thickened basal lamina. Reactive
      microglia is found in close association with retinal capillaries. In older
      animals, loss of endothelial cells and the formation of ghost vessels are
      observed, findings that correlate with the induction of angiogenic molecules and
      the accumulation of retinal hypoxia-inducible factor 1alpha, indicating hypoxia.
      Consequently, retinal and vitreal neovascularization occurs, a scenario that
      leads to retinal detachment, vitreal hemorrhages, neuronal apoptosis, and
      impairment of sensory function. We conclude that transforming growth factor beta
      signaling is required for the differentiation of retinal pericytes during
      vascular development of the retina. Lack of differentiated pericytes initiates a
      scenario of structural and functional changes in the retina that mimics those of
      diabetic retinopathy strongly indicating a common mechanism.

PMID- 25857228
TI  - Pathophysiological function of endogenous calcitonin gene-related peptide in
      ocular vascular diseases.
AB  - Calcitonin gene-related peptide (CGRP; official name CALCA) has a variety of
      functions and exhibits both angiogenic and anti-inflammatory properties. We
      previously reported the angiogenic effects of the CGRP family peptide
      adrenomedullin in oxygen-induced retinopathy; however, the effects of CGRP on
      ocular angiogenesis remain unknown. Herein, we used CGRP knockout (CGRP(-/-))
      mice to investigate the roles of CGRP in ocular vascular disease. Observation of
      pathological retinal angiogenesis in the oxygen-induced retinopathy model
      revealed no difference between CGRP(-/-) and wild-type mice. However, much higher
      levels of the CGRP receptor were present in the choroid than the retina. Laser
      induced choroidal neovascularization (CNV), a model of exudative age-related
      macular degeneration, revealed more severe CNV lesions in CGRP(-/-) than wild
      type mice, and fluorescein angiography showed greater leakage from CNV in CGRP(-/
      ). In addition, macrophage infiltration and tumor necrosis factor (TNF)-alpha
      production were enhanced within the CNV lesions in CGRP(-/-) mice, and the TNF
      alpha, in turn, suppressed the barrier formation of retinal pigment epithelial
      cells. In vivo, CGRP administration suppressed CNV formation, and CGRP also dose
      dependently suppressed TNF-alpha production by isolated macrophages. From these
      data, we conclude that CGRP suppresses the development of leaky CNV through
      negative regulation of inflammation. CGRP may thus be a promising therapeutic
      agent for the treatment of ocular vascular diseases associated with inflammation.

PMID- 25857230
TI  - Reflecting on 'Analytical perspectives on performance-based management: an
      outline of theoretical assumptions in the existing literature'.

PMID- 25857229
TI  - Autoimmune pathogenesis of Chagas heart disease: looking back, looking ahead.
AB  - Chagas heart disease is an inflammatory cardiomyopathy that develops in
      approximately one-third of individuals infected with the protozoan parasite
      Trypanosoma cruzi. Since the discovery of T. cruzi by Carlos Chagas >100 years
      ago, much has been learned about Chagas disease pathogenesis; however, the
      outcome of T. cruzi infection is highly variable and difficult to predict. Many
      mechanisms have been proposed to promote tissue inflammation, but the
      determinants and the relative importance of each have yet to be fully elucidated.
      The notion that some factor other than the parasite significantly contributes to
      the development of myocarditis was hypothesized by the first physician-scientists
      who noted the conspicuous absence of parasites in the hearts of those who
      succumbed to Chagas disease. One of these factors-autoimmunity-has been
      extensively studied for more than half a century. Although questions regarding
      the functional role of autoimmunity in the pathogenesis of Chagas disease remain
      unanswered, the development of autoimmune responses during infection clearly
      occurs in some individuals, and the implications that this autoimmunity may be
      pathogenic are significant. In this review, we summarize what is known about the
      pathogenesis of Chagas heart disease and conclude with a view of the future of
      Chagas disease diagnosis, pathogenesis, therapy, and prevention, emphasizing
      recent advances in these areas that aid in the management of Chagas disease.

PMID- 25857231
TI  - Organic anion transporting polypeptide 2B1 expression correlates with uptake of
      estrone-3-sulfate and cell proliferation in estrogen receptor-positive breast
      cancer cells.
AB  - Estrone-3-sulfate (E1S) is thought to be a major estrogen precursor in estrogen
      receptor (ER)-positive breast cancer. Since E1S is a hydrophilic compound, the
      uptake of E1S into cancer cells is probably mediated by transporters, such as
      organic anion-transporting polypeptide (OATP, SLCO) family. In this study, we
      investigated the relationship between expression of OATP2B1 and cell
      proliferation in ER-positive breast cancer. Cell-based assays were carried out in
      MCF-7 cells both with and without overexpression of OATP2B1. Normal breast and
      tumor tissues were collected and used in this study. Cell proliferation, ER
      mediated transcriptional activities and estradiol secretion were stimulated by
      addition of E1S to the culture medium of MCF-7 cells. These stimulatory effects
      were significantly greater in MCF-7 cells overexpressing OATP2B1 than in control
      cells. The expression level of SLCO2B1 mRNA was significantly correlated with
      histological grade, Ki-67 labelling index and mRNA expression of steroid
      sulfatase. The expression level of SLCO2B1 mRNA in luminal B-like cancers was
      higher than that in luminal A-like cancers. Uptake of E1S resulted in down
      regulation of ERalpha protein and induction of Ki-67 in MCF-7 cells. The present
      study suggests that OATP2B1 is involved in cell proliferation by increasing the
      amount of estrogen in ER-positive breast cancer cells. 

PMID- 25857232
TI  - In vivo absorption and disposition of alpha-cedrene, a sesquiterpene constituent
      of cedarwood oil, in female and male rats.
AB  - This study aimed to evaluate the potential of alpha-cedrene as a new anti-obesity
      drug by characterizing absorption, metabolism and pharmacokinetics in rats. alpha
      Cedrene was administered intravenously (10 and 20 mg/kg) and orally (50 and 100
      mg/kg) to female and male Sprague-Dawley rats. Blood, tissues, urine, and feces
      were collected at predetermined times. alpha-Cedrene concentrations were
      determined by a validated gas chromatography-tandem mass spectrometry (GC-MS/MS).
      A gas chromatography-mass selective detection (GC-MSD) method was used to
      identify the major metabolite. After i.v. injection, alpha-cedrene exhibited a
      rapid clearance (98.4-120.3 ml/min/kg), a large distribution volume (35.9-56.5
      l/kg), and a relatively long half-life (4.0-6.4 h). Upon oral administration, it
      was slowly absorbed (Tmax = 4.4 h) with bioavailability of 48.7-84.8%. No gender
      differences were found in its pharmacokinetics. Upon oral administration, alpha
      cedrene was highly distributed to tissues, with the tissue-to-plasma partition
      coefficients (Kp) far greater than unity for all tissues. In particular, its
      distribution to lipid was notably high (Kp = 132.0) compared to other tissues. A
      mono-hydroxylated metabolite was identified as a preliminary metabolite in rat
      plasma. These results suggest that alpha-cedrene has the favorable
      pharmacokinetic characteristics to be further tested as an anti-obesity drug in
      clinical studies.

PMID- 25857233
TI  - Inhibition effects of Vernonia cinerea active compounds against cytochrome P450
      2A6 and human monoamine oxidases, possible targets for reduction of tobacco
      dependence.
AB  - The human cytochrome P450 2A6 (CYP2A6) and monoamine oxidases (MAO-A and MAO-B),
      catalyzing nicotine and dopamine metabolisms, respectively, are two therapeutic
      targets of nicotine dependence. Vernonia cinerea, a medicinal plant commonly used
      for treatment of diseases such as asthma and bronchitis, has been shown reducing
      tobacco dependence effect among tobacco users. In the present study, we found
      eight active compounds isolated from V. cinerea that comprise inhibitory activity
      toward CYP2A6 and MAO-A and MAO-B enzymes using activity-guided assays, with
      coumarin as substrate of CYP2A6 and kynuramine of MAOs. These compounds were
      three flavones (apigenin, chrysoeriol, luteolin), one flavonol (quercetin), and
      four hirsutinolide-type sesquiterpene lactones (8alpha-(2-methylacryloyloxy)
      hirsutinolide-13-O-acetate, 8alpha-(4-hydroxymethacryloyloxy)-hirsutinolide-13-O
      acetate, 8alpha-tigloyloxyhirsutinolide-13-O-acetate, and 8alpha-(4
      hydroxytigloyloxy)-hirsutinolide-13-O-acetate). Modes and kinetics of inhibition
      against the three enzymes were determined. Flavonoids possessed strong inhibitory
      effect on CYP2A6 in reversible mode, while inhibition by hirsutinolides was
      mechanism-based (NADPH-, concentration-, and time-dependence) and irreversible.
      Inhibition by hirsutinolides could not be reversed by dialysis and by addition of
      trapping agents or potassium ferricyanide. Flavonoids inhibited MAOs with
      variable degrees and were more prominent in inhibition toward MAO-A than
      hirsutinolides, while two of hirsutinolides inhibited MAO-B approximately
      comparable to two flavonoids. These results could have implications in
      combination of drug therapy for smoking cessation.

PMID- 25857234
TI  - Memantine transport by a proton-coupled organic cation antiporter in hCMEC/D3
      cells, an in vitro human blood-brain barrier model.
AB  - Memantine is clinically used for the treatment of patients with Alzheimer's
      disease and is highly distributed to the brain. The aim of this study is to
      characterize memantine transport at the blood-brain barrier (BBB) using hCMEC/D3
      cells, a human BBB model. The initial uptake velocity of memantine in hCMEC/D3
      cells was concentration-dependent, and was reduced by metabolic inhibitors, but
      was independent of extracellular sodium ion and membrane potential. Intracellular
      alkalization and intracellular acidification markedly reduced and enhanced the
      uptake, respectively. The uptake was strongly inhibited by quinidine, pyrilamine
      and verapamil, and was moderately inhibited by TEA (substrate of OCTs and OCTNs)
      and l-carnitine (substrate of OCTN2), but was not inhibited by MPP(+) (substrate
      of OCTs and PMAT) or ergothioneine (substrate of OCTN1). Although relatively
      abundant expression of OCTN2 gene has been observed in hCMEC/D3 cells, knockdown
      of OCTN2 with siRNA did not decrease memantine uptake. Memantine and
      diphenhydramine each showed inhibition of the other's uptake in a competitive
      manner. Thus, proton-coupled organic cation antiporter(s) appears to be involved
      in the transport of memantine in hCMEC/D3 cells, at least in part. Our results
      indicate that the in vivo BBB permeability of memantine in humans can be
      predicted from the in vitro uptake clearance in hCMEC/D3 cells.

PMID- 25857235
TI  - Inter-individual relationships in empathic traits and feedback-related fronto
      central brain activity: an event-related potential study.
AB  - BACKGROUND: Neuroimaging studies continue to indicate the major role the anterior
      cingulate cortex (ACC) plays in processing empathic responses. Error-related
      negativity (ERN), an event-related potential (ERP) thought to arise from the ACC,
      has been found to correlate with scores for individual empathic personality. This
      study investigated the relationship between empathic personality traits and the
      amplitude of feedback-related negativity (FRN), an ERP sourced from the ACC and
      similar to the ERN, using a task involving feedback of monetary gains or losses.
      METHODS: Sixteen healthy participants answered an empathy trait questionnaire and
      performed a gambling task to elicit FRN. Because FRN amplitude is thought to be
      associated with attention, motivation, emotional state, and anxiety trait, we
      performed a partial correlation analysis between the empathic trait score and FRN
      amplitude while controlling for variables. RESULTS: In partial correlation
      analysis, FRN amplitude was significantly inversely correlated with scores for
      personal distress and marginally correlated with scores for empathic concern and
      with total average score. DISCUSSION: The study revealed for the first time an
      association between FRN and emotional empathic traits, after controlling for
      variables that can affect FRN amplitude. However, we also found a reversed
      directional correlation contrary to our expectations. This fronto-central brain
      activity may be associated with empathic properties via dopaminergic neuronal
      function. Future study using these electric potentials as experimental tools is
      expected to help elucidate the neurological mechanism of empathy.

PMID- 25857239
TI  - 5(th) International Workshop on CMV and Immunosenescence - A shadow of
      cytomegalovirus infection on immunological memory.

PMID- 25857236
TI  - Vaccines for the prevention of seasonal influenza in patients with diabetes:
      systematic review and meta-analysis.
AB  - BACKGROUND: Patients with diabetes are at increased risk of severe influenza
      disease; influenza vaccination for these patients is therefore recommended by the
      World Health Organization and several National Immunization Technical Advisory
      Groups. However, no systematic review has evaluated the effects of influenza
      vaccines for patients with diabetes. METHODS: We conducted a systematic review
      and meta-analysis by searching Medline, Embase, Cochrane Central Register of
      Controlled Trials, and ClinicalTrials.gov from inception until November 2014. We
      included all types of studies reporting on the efficacy, effectiveness, and/or
      safety of influenza vaccination in patients with type 1 and type 2 diabetes of
      all ages. We used the Newcastle-Ottawa scale to assess risk of bias in
      observational studies. Residual confounding was addressed by comparing estimates
      of vaccine effectiveness (VE) during influenza seasons to those obtained during
      off-seasons. Quality of the evidence for each outcome was assessed using the
      GRADE methodology. RESULTS: Following review of 1,444 articles, 11 observational
      studies with a total of 170,924 participants were included. In diabetic patients
      of working-age (18-64 years), influenza vaccination prevented all-cause
      hospitalization with a pooled VE of 58% (95% CI, 6-81%) and hospitalization due
      to influenza or pneumonia (VE 43%; 95% CI, 28-54%), whereas no effects on all
      cause mortality and influenza-like illness (ILI) were observed. In the elderly
      (65+), influenza vaccination prevented all-cause mortality (VE 38%; 95% CI, 32
      43%), all-cause hospitalization (VE 23%; 95% CI, 1-40%), hospitalization due to
      influenza or pneumonia (VE 45%; 95% CI, 34-53%), and ILI (VE 13%; 95% CI, 10
      16%). However, significant off-season estimates for several outcomes indicated
      residual confounding, particularly in elderly patients. Quality of the evidence
      was low to very low for all outcomes. Laboratory-confirmed influenza infections
      were not reported. CONCLUSIONS: Due to strong residual confounding in most of the
      identified studies, the available evidence is insufficient to determine the
      magnitude of benefit that diabetic people derive from seasonal influenza
      vaccination. Adequately powered randomized controlled trials or quasi
      experimental studies using laboratory-confirmed influenza-specific outcomes are
      urgently needed.

PMID- 25857244
TI  - Effective removal of humic acid using xanthan gum incorporated polyethersulfone
      membranes.
AB  - In this study, xanthan gum (XA) was used as a hydrophilic biopolymer additive for
      the modification of polyethersulfone (PES) membrane to removal of humic acid
      (HA). The membranes are prepared using phase inversion technique and the
      concentration of XA was varied from 0.5 to 1.5wt%. The prepared membranes are
      characterized as a function of hydrophilicity, equilibrium water content (EWC),
      porosity studies and functional group analysis. Membrane surface and cross
      sectional morphology was studied using scanning electron microscope. The lower
      contact angle value 64.2 degrees  was exhibited, when 1.5wt% of XA incorporated
      in PES membrane and this ensures that increase of hydrophilicity in pristine PES
      membrane. Further, higher water permeability (PWP) of 68.9(-9)m/skPa was observed
      for 1.5wt% of XA/PES membrane. The effect of pH on HA removal was studied for
      neat PES and XA/PES membranes. The rejection performance of XA incorporated in
      PES membranes were compared with commercial available PES membrane. 

PMID- 25857245
TI  - EGFR-directed antibodies increase the risk of severe infection in cancer
      patients.
AB  - Monoclonal antibodies directed to the epidermal growth factor receptor (EGFR)
      have a role in the management of several solid tumors, alone or in combination
      with chemotherapy or radiation therapy. Recognized toxicities have included
      hypersensitivity reactions, rash, hypomagnesemia, and constitutional symptoms,
      but the possibility that the agents lead to immunosuppression or increase the
      risk of infection has only recently been recognized. Two latest meta-analyses,
      including the recently published article by Qi et al., highlight the increased
      risk of severe infections with EGFR-directed monoclonal antibodies. Further
      studies are needed to better identify the association between EGFR-directed
      monoclonal antibody treatment and infection, as well as to elucidate the
      mechanism of this toxicity and to develop tools to identify patients at increased
      risk for these complications. In the meantime, awareness of the role of EGFR
      directed antibodies in increased infection risk may have implications for dose
      modification strategies in both clinical trial design and the practice of
      oncology. Please see related article: http://www.biomedcentral.com/1741
      7015/12/203.

PMID- 25857246
TI  - Reanalysis of the DEMS nested case-control study of lung cancer and diesel
      exhaust: suitability for quantitative risk assessment.
AB  - The International Agency for Research on Cancer (IARC) in 2012 upgraded its
      hazard characterization of diesel engine exhaust (DEE) to "carcinogenic to
      humans." The Diesel Exhaust in Miners Study (DEMS) cohort and nested case-control
      studies of lung cancer mortality in eight U.S. nonmetal mines were influential in
      IARC's determination. We conducted a reanalysis of the DEMS case-control data to
      evaluate its suitability for quantitative risk assessment (QRA). Our reanalysis
      used conditional logistic regression and adjusted for cigarette smoking in a
      manner similar to the original DEMS analysis. However, we included additional
      estimates of DEE exposure and adjustment for radon exposure. In addition to
      applying three DEE exposure estimates developed by DEMS, we applied six
      alternative estimates. Without adjusting for radon, our results were similar to
      those in the original DEMS analysis: all but one of the nine DEE exposure
      estimates showed evidence of an association between DEE exposure and lung cancer
      mortality, with trend slopes differing only by about a factor of two. When
      exposure to radon was adjusted, the evidence for a DEE effect was greatly
      diminished, but was still present in some analyses that utilized the three
      original DEMS DEE exposure estimates. A DEE effect was not observed when the six
      alternative DEE exposure estimates were utilized and radon was adjusted. No
      consistent evidence of a DEE effect was found among miners who worked only
      underground. This article highlights some issues that should be addressed in any
      use of the DEMS data in developing a QRA for DEE. 

PMID- 25857248
TI  - An efficient total synthesis of leukotriene B4.
AB  - Lipid mediators have attracted great interest from scientists within the
      chemical, medicinal, and pharmaceutical research community. One such example is
      leukotriene B4 which has been the subject of many pharmacological studies.
      Herein, we report a convergent and stereoselective synthesis of this potent lipid
      mediator in 5% yield over 10 steps in the longest linear sequence from commercial
      starting materials. The key steps were a stereocontrolled acetate-aldol reaction
      with Nagao's chiral auxiliary and a Z-selective Boland reduction. All
      spectroscopic data were in agreement with those previously reported. 

PMID- 25857247
TI  - Complications in children from foreign bodies in the airway.
AB  - INTRODUCTION AND OBJECTIVES: Foreign body aspiration in childhood is a common and
      potentially serious problem. Complications may be the result of the aspiration
      episode itself, delayed diagnosis or treatment. We describe our experience in a
      paediatric hospital in Argentina. METHODS: We retrospectively evaluated 56
      patients with complications due to foreign body aspiration recorded in the Susy
      Safe Project between January 2010 and November 2013. The clinical variables
      analysed were sex, age at time of aspiration, foreign body location and type,
      time elapsed from the event until object removal, extraction technique,
      complications, need for hospitalisation and circumstances of the event. RESULTS:
      58.9% of the cases described occurred in males, with high presence of adults
      (76.8%) at the time of aspiration. The incidence was slightly higher in children
      older than 3 years. In 37 cases (66.1%), the foreign body was located in
      bronchus; sunflower seeds and ballpoint caps were the most common foreign
      objects. Only in 10 cases (17.9%) was the object extracted within 24h of the
      event. The most common complications were pneumonia (18 cases), granuloma (15
      cases) and mucosal erosion (9 cases). Hospitalisation was necessary for 41
      patients. CONCLUSION: Early diagnosis and immediate control through specialised
      teams are essential to ensure proper treatment, usually endoscopic, without risk
      of complications.

PMID- 25857249
TI  - [Study of patients with prolonged fever with (18)F-FDG PET/CT].
AB  - OBJECTIVE: To review the findings on (18)F-FDG PET-CT in patients with fever of
      unknown origin lasting more than 7 days. MATERIAL AND METHODS: This retrospective
      descriptive observational study included 93 (18)F-FDG PET-CT studies to detect a
      fever-causing focus done at three nuclear medicine centers from October 2006
      through February 2014. A nuclear medicine specialist and a radiologist reviewed
      the images for foci of pathological uptake; another specialist's opinion resolved
      discrepancies. The findings on (18)F-FDG PET-CT studies were checked against
      clinical and/or histological findings. RESULTS: Abnormal (18)F-FDG uptake on PET
      CT that could explain the cause of the fever was found in 52 (56%) of the 93
      studies, and the cause of the fever was confirmed in 50 of these 52 studies. In
      the 50 cases in which the cause of the fever was confirmed, infection was the
      most common cause (54%), followed by noninfectious inflammatory disease (28%) and
      tumors (18%). CONCLUSION: (18)F-FDG PET-CT is useful in diagnosing the cause of
      prolonged febrile illness, so it might be practical to use it earlier in the
      diagnostic process.

PMID- 25857250
TI  - Trans-arterial chemoembolization with doxorubicin-eluting particles versus
      conventional trans-arterial chemoembolization in unresectable hepatocellular
      carcinoma: A study of effectiveness, safety and costs.
AB  - OBJECTIVES: To compare the effectiveness, survival and cost in patients with
      unresectable hepatic cell carcinoma (HCC) treated with trans-arterial
      chemoembolization using doxorubicin-eluting beads (DEB-TACE) versus conventional
      TACE (cTACE) in clinical practice. MATERIAL AND METHODS: This single-centered
      retrospective observational study compared 60 consecutive HCC unresectable
      patients: 30 were treated with DEB-TACE and 30 used cTACE. Comparisons were with
      chi(2) test, Student t-test, and Kaplan Meier method. RESULTS: Of the 60 patients
      with HCC in non-curative stage, baseline characteristics were similar for both
      groups of treatment, and of these we observed lower survival in male patients and
      those who had hepatitis C virus (p=0.014 and p=0.003, respectively). No
      statistically significant differences were observed as a function of treatment
      employed with respect to overall survival (OS) at 5 years (29.99 months; 95%CI:
      21.38-38.60 versus 30.67 months; 95%CI:22.65-38.70; p=0.626) and progression free
      survival (PFS) median of 11.57 months (95%CI: 0.97-22.18) versus 12.80 months
      (95%CI:0.00-32.37; p=0.618). The median length of hospital admission were 2.6 and
      5.4 days (p<0.001) for DEB(-)TACE and cTACE, respectively. Toxicities grade 2-4
      were higher in cTACE group (54 versus 31; p<0.001). The cost of the treatment was
      1581 ? for DEB(-)TACE and 514.63 ? for cTACE. The overall mean cost of
      intervention was 3134 ? and 3694.35 ?, respectively (p=0.173). CONCLUSIONS:
      Chemoembolization in patients with unresectable HCC achieved OS close to 30
      months at 5 years, independent of the technique employed. Similar overall costs
      but better tolerance of the DEB-TACE justified the higher costs of the procedure.

PMID- 25857251
TI  - Thoracodorsal artery perforator - scapular flap in oromandibular reconstruction
      with associated large facial skin defects.
AB  - The reconstruction of oromandibular defects associated with extensive loss of
      external skin is surgically challenging. We describe 2 cases where such defects
      were reconstructed with a chimeric thoracodorsal artery perforator and scapular
      (TDAP-Scap) free flap based on the subscapular system. The flap is a reliable
      option in the reconstruction of through-and-through oromandibular defects. 

PMID- 25857252
TI  - alpha1 -Adrenoceptor activation of PKC-epsilon causes heterologous
      desensitization of thromboxane receptors in the aorta of spontaneously
      hypertensive rats.
AB  - BACKGROUND AND PURPOSE: In the aorta of adult spontaneously hypertensive (SHR),
      but not in that of normotensive Wistar-Kyoto (WKY), rats, previous exposure to
      phenylephrine inhibits subsequent contractions to PGE2 . The present experiments
      were designed to examine the mechanism(s) underlying this inhibition.
      EXPERIMENTAL APPROACH: Isometric tension was measured in isolated rings of SHR
      and WKY aortae. Gene expression and protein presence were measured by
      quantitative real-time PCR and Western blotting respectively. KEY RESULTS: In
      aorta of 18 weeks SHR, but not age-matched WKY, pre-exposure to phenylephrine
      inhibited subsequent contractions to PGE2 that were mediated by thromboxane
      prostanoid (TP) receptors. This inhibition was not observed in preparations of
      pre-hypertensive 5-week-old SHR, and was significantly larger in those of 36-
      than 18-week-old SHR. Pre-exposure to the PKC activator, phorbol 12,13
      dibutyrate, also inhibited subsequent contractions to PGE2 in SHR aortae. The
      selective inhibitor of PKC-epsilon, epsilon-V1-2, abolished the desensitization
      caused by pre-exposure to phenylephrine. Two molecular PKC bands were detected
      and their relative intensities differed in 36-week-old WKY and SHR vascular
      smooth muscle. The mRNA expressions of PKC-alpha, PKC-epsilon, PK-N2 and PKC-zeta
      and of G protein-coupled kinase (GRK)-2, GRK4 and beta-arrestin2 were higher in
      SHR than WKY aortae. CONCLUSIONS AND IMPLICATIONS: These experiments suggest that
      in the SHR but not the WKY aorta, alpha1 -adrenoceptor activation desensitizes TP
      receptors through activation of PKC-epsilon. This heterologous desensitization is
      a consequence of the chronic exposure to high arterial pressure.

PMID- 25857253
TI  - The hippocampus and TNF: Common links between chronic pain and depression.
AB  - Major depression and chronic pain are significant health problems that seriously
      impact the quality of life of affected individuals. These diseases that
      individually are difficult to treat often co-exist, thereby compounding the
      patient's disability and impairment as well as the challenge of successful
      treatment. The development of efficacious treatments for these comorbid disorders
      requires a more comprehensive understanding of their linked associations through
      common neuromodulators, such as tumor necrosis factor-alpha (TNFalpha), and
      various neurotransmitters, as well as common neuroanatomical pathways and
      structures, including the hippocampal brain region. This review discusses the
      interaction between depression and chronic pain, emphasizing the fundamental role
      of the hippocampus in the development and maintenance of both disorders. The
      focus of this review addresses the hypothesis that hippocampal expressed TNFalpha
      serves as a therapeutic target for management of chronic pain and major
      depressive disorder (MDD). 

PMID- 25857255
TI  - In vitro evaluation of six chemical agents on smooth Brucella melitensis strain.
AB  - Brucellosis is a zoonosis that disseminated by a variety of ways between animals
      and humans. The effective disinfection of contaminated environments, soil, feces,
      and animal bodies plays an irreplaceable role in the prevention and control of
      brucellosis. To kill Brucella effectively, the bactericidal effects of frequently
      used disinfectants (including aldehydes, halogens, quaternary ammonium compound,
      phenolics, and alkalines) and the potential factors that influence disinfection
      effects were determined in the present study. The results revealed that the
      minimum bactericidal concentrations (MBCs) of the six disinfectants were all
      significantly lower than the routinely used concentrations, and all the tested
      disinfectants were effective against B. melitensis NI. The results of
      quantitative determination showed that the bactericidal effects of the
      disinfectants were influenced by their concentration, exposure time, dirty
      condition and the temperature. Under dirty conditions and a low temperatures,
      sodium hypochlorite and sodium hydroxide showed better bactericidal effect, while
      benzalkonium chloride was almost without bactericidal ability. In addition,
      increasing the disinfectant concentration at low temperatures can improve the
      bactericidal effect. The present study suggested that Brucella is sensitive to
      commonly used disinfectants. However, the bactericidal effect is vulnerable to
      dirty conditions and low temperatures. Thus, it is necessary to test the in vitro
      sensitivity of disinfectants that are commonly used on farms or the new
      disinfectant formulations periodically, with the aim of improving the efficacy of
      animal and human brucellosis prevention programs. 

PMID- 25857254
TI  - Neurocognitive outcomes in long-term survivors of childhood acute lymphoblastic
      leukemia treated on contemporary treatment protocols: A systematic review.
AB  - The intensified administration of chemotherapeutic drugs has gradually replaced
      cranial radiation therapy (CRT) for the treatment of childhood acute
      lymphoblastic leukemia (ALL). While CRT is often implicated in neurocognitive
      impairment in ALL survivors, there is a paucity of the literature that evaluates
      the persistence of neurocognitive deficits in long-term survivors of pediatric
      ALL who were treated with contemporary chemotherapy-only protocols. Results from
      this systematic review concurred to the probable cognitive-sparing effect of
      chemotherapy-based protocols over CRT in long-term survivors. However, coupled
      with multiple intrinsic and extrinsic factors, survivors who received
      chemotherapy treatment still suffered from apparent cognitive impairment,
      particularly in the attention and executive function domains. Notably, there is
      evidence to suggest that the late neurotoxic effect of methotrexate on survivors'
      neurocognitive performance may be dose-related. This review also recommends
      future pharmacokinetic, neuroimaging and genetic studies to illuminate the
      multifactorial nature of this subject matter and discusses the potential value of
      neurochemical, physiological, inflammatory and genetic markers for the prediction
      of susceptibility to neurocognitive impairment in long-term survivors of
      childhood ALL. 

PMID- 25857256
TI  - Neuroprotective effects of alkaloids from Piper longum in a MPTP-induced mouse
      model of Parkinson's disease.
AB  - CONTEXT: Alkaloids of Piper longum L. (Piperaceae) (PLA) include piperine and
      piperlonguminine. Piper longum and piperine have multiple biological properties
      including antioxidant activity. OBJECTIVE: The present study investigated the
      neuroprotective effects of PLA in a MPTP-induced mouse model of Parkinson's
      disease. MATERIALS AND METHODS: PLA was prepared by extracting the dry seed of P.
      longum using 85% ethanol. Adult male C57BL/6 mice were divided into eight groups
      of 12 rats each. Experimental and control groups received an equivalent volume of
      saline, 0.5% CMC-Na, and 0.1% Tween 80, treated groups received oral PLA (30, 60,
      and 120 mg/kg), other groups treated with piperine (60 mg/kg) or Madopar (50
      mg/kg). The PLA prevention group (PLA-Pr) administrated PLA (120 mg/kg) for 1
      week before MPTP challenged. Except for the PLA-Pr group, others were treated for
      seven consecutive weeks. Parkinson's disease was induced by injecting MPTP
      intraperitoneally (25 mg/kg) twice weekly for five consecutive weeks.
      Dopaminerigic (DA) neurons and their metabolism were detected by UFLC-MS/MS.
      Tyrosine hydroxylase (TH)-immunohistochemistry assay and Western blotting were
      performed. The antioxidant enzymatic levels were determined by kit-based assays.
      RESULTS: The LD50 value of PLA was determined at 1509 mg/kg of body weight. PLA
      (60 mg/kg) can significantly increase total movement time and distance (p <
      0.05), increase levels of DA (p < 0.05) and DOPAC (p <  .05), increase
      glutathione (GSH) level and superoxide dismutase (SOD) activity (p < 0.05), and
      decrease the lipid peroxidation of malondiadehycle (MDA) (p < 0.05) in PLA
      treated groups as compared with the control group. DISCUSSION AND CONCLUSION: Our
      results indicate that PLA possesses neuroprotective effects and has ameliorative
      properties in dopaminergic neurons.

PMID- 25857257
TI  - NHLBI viewpoint: Lung health and disease prevention research starting in
      childhood.
AB  - Lung health begins in utero when the complex structure of the airway, alveolar,
      and vascular structures are formed. To really impact the United States and global
      burden of chronic lung diseases in both adults and children, we must understand
      normal and abnormal development, the outcomes of disrupted development, and the
      effects of in utero and postnatal exposures on lung health. With increasing
      recognition of early life origins of adult diseases,(1) it is important to know
      what early events and interventions can alter the trajectory of lung development,
      growth, and decline to help promote lung health and reduce chronic lung disease.

PMID- 25857258
TI  - Co-morbid psychiatric disorders among incarcerated ADHD populations: a meta
      analysis.
AB  - BACKGROUND: Rates of psychiatric disorders are highly prevalent among prison
      inmates, and recent evidence confirms over-representation of youths and adults
      with attention deficit hyperactivity disorder (ADHD). The risk for psychiatric co
      morbidity may be greater among offenders with ADHD. We undertook a systematic
      review and meta-analysis of reported rates of co-existing psychiatric morbidity
      with ADHD in prison samples. METHOD: Studies published from 1980 to 2015 were
      identified using five bibliographic indexes, review articles and reference lists.
      Included studies had a defined ADHD group and provided additional prevalence on
      at least one of the following: conduct disorder, substance use disorder, mood
      disorder, anxiety disorder, or personality disorder. We performed meta-analytical
      estimates of the prevalence of each co-morbid disorder within ADHD, and estimated
      the risk for co-existing disorders among prisoners with ADHD by pooling odds
      ratios (OR) with 95% confidence intervals. RESULTS: Eighteen studies with data
      for 1615 with ADHD and 3128 without ADHD were included. The risk (OR) of all
      psychiatric morbidity is increased among adult inmates with ADHD. Associations in
      youths with ADHD were restricted to mood disorder (OR 1.89, 95% confidence
      interval 1.09-3.28). CONCLUSIONS: This study quantifies the extent of co
      morbidity presented by offenders with ADHD, especially adults. The differences
      between risk estimates for youths and adults indicate an incremental effect in
      both frequency and severity for the development of further co-morbid pathology
      through adulthood. The findings have implications for clinical intervention and
      for criminal justice policy.

PMID- 25857260
TI  - Structure and biosynthesis of fumosorinone, a new protein tyrosine phosphatase 1B
      inhibitor firstly isolated from the entomogenous fungus Isaria fumosorosea.
AB  - Fumosorinone, isolated from the entomogenous fungus Isaria fumosorosea, is a new
      2-pyridone alkaloid which is elucidated by HRESIMS 1D and 2DNMR. Fumosorinone is
      structurally similar to tenellin and desmethylbassianin but it differs in chain
      length and degree of methylation. It is characterized by a classic noncompetitive
      inhibitor of protein tyrosine phosphatase 1B (IC50 14.04MUM) which was implicated
      as a negative regulator of insulin receptor signaling and a potential drug target
      for the treatment of type II diabetes and other associated metabolic syndromes.
      For further study, we identified the biosynthetic gene cluster of fumosorinone
      from ongoing genome sequencing project, and it was verified by a direct knock-out
      strategy, reported for the first time in I. fumosorosea, using the Agrobacterium
      mediated transformation in conjunction with linear deletion cassettes. The
      biosynthetic gene cluster includes a hybrid polyketide synthase-nonribosomal
      peptide synthetase gene, two cytochrome P450 enzyme genes, a trans-enoyl
      reductase gene, and other two transcription regulatory genes. Comparison of
      fumosorinone biosynthetic cluster with known gene clusters gives further insight
      into biosynthesis of pyridone alkaloids and provides the foundation for
      combinatorial biosynthesis for new fumosorinone derivatives. 

PMID- 25857259
TI  - Chromatin analyses of Zymoseptoria tritici: Methods for chromatin
      immunoprecipitation followed by high-throughput sequencing (ChIP-seq).
AB  - The presence or absence of specific transcription factors, chromatin remodeling
      machineries, chromatin modification enzymes, post-translational histone
      modifications and histone variants all play crucial roles in the regulation of
      pathogenicity genes. Chromatin immunoprecipitation (ChIP) followed by high
      throughput sequencing (ChIP-seq) provides an important tool to study genome-wide
      protein-DNA interactions to help understand gene regulation in the context of
      native chromatin. ChIP-seq is a convenient in vivo technique to identify, map and
      characterize occupancy of specific DNA fragments with proteins against which
      specific antibodies exist or which can be epitope-tagged in vivo. We optimized
      existing ChIP protocols for use in the wheat pathogen Zymoseptoria tritici and
      closely related sister species. Here, we provide a detailed method, underscoring
      which aspects of the technique are organism-specific. Library preparation for
      Illumina sequencing is described, as this is currently the most widely used ChIP
      seq method. One approach for the analysis and visualization of representative
      sequence is described; improved tools for these analyses are constantly being
      developed. Using ChIP-seq with antibodies against H3K4me2, which is considered a
      mark for euchromatin or H3K9me3 and H3K27me3, which are considered marks for
      heterochromatin, the overall distribution of euchromatin and heterochromatin in
      the genome of Z. tritici can be determined. Our ChIP-seq protocol was also
      successfully applied to Z. tritici strains with high levels of melanization or
      aberrant colony morphology, and to different species of the genus (Z. ardabiliae
      and Z. pseudotritici), suggesting that our technique is robust. The methods
      described here provide a powerful framework to study new aspects of chromatin
      biology and gene regulation in this prominent wheat pathogen. 

PMID- 25857261
TI  - Fluorescent markers of the microtubule cytoskeleton in Zymoseptoria tritici.
AB  - The microtubule cytoskeleton supports vital processes in fungal cells, including
      hyphal growth and mitosis. Consequently, it is a target for fungicides, such as
      benomyl. The use of fluorescent fusion proteins to illuminate microtubules and
      microtubule-associated proteins has led to a break-through in our understanding
      of their dynamics and function in fungal cells. Here, we introduce fluorescent
      markers to visualize microtubules and accessory proteins in the wheat pathogen
      Zymoseptoria tritici. We fused enhanced green-fluorescent protein to alpha
      tubulin (ZtTub2), to ZtPeb1, a homologue of the mammalian plus-end binding
      protein EB1, and to ZtGrc1, a component of the minus-end located gamma-tubulin
      ring complex, involved in the nucleation of microtubules. In vivo observation
      confirms the localization and dynamic behaviour of all three markers. These
      marker proteins are useful tools for understanding the organization and
      importance of the microtubule cytoskeleton in Z. tritici. 

PMID- 25857262
TI  - Assessment of radiocesium contamination in frogs 18 months after the Fukushima
      Daiichi nuclear disaster.
AB  - We investigated the accumulation of radionuclides in frogs inhabiting
      radioactively contaminated areas around Fukushima Daiichi Nuclear Power Plant
      (FDNPP) to search for possible adverse effects due to radionuclides. We collected
      5 frog species and soil samples in areas within and outside a 20-km radius from
      FDNPP in August and September 2012 and determined their radiocesium
      concentrations ((134)Cs and (137)Cs). There was a positive correlation between
      radiocesium concentrations in the soil samples and frogs, and the highest
      concentration in frogs was 47,278.53 Bq/kg-wet. Although we conducted a
      histological examination of frog ovaries and testes by light microscopy to detect
      possible effects of radionuclides on the morphology of germ cells, there were no
      clear abnormalities in the gonadal tissues of frogs collected from sites with
      different contamination levels. 

PMID- 25857263
TI  - MYB controls erythroid versus megakaryocyte lineage fate decision through the miR
      486-3p-mediated downregulation of MAF.
AB  - The transcription factor MYB has a key role in hematopoietic progenitor cells
      (HPCs) lineage choice, by enhancing erythropoiesis at the expense of
      megakaryopoiesis. We previously demonstrated that MYB controls erythroid versus
      megakaryocyte lineage decision by transactivating KLF1 and LMO2 expression. To
      further unravel the molecular mechanisms through which MYB affects lineage fate
      decision, we performed the integrative analysis of miRNA and mRNA changes in MYB
      silenced human primary CD34+ HPCs. Among the miRNAs with the highest number of
      predicted targets, we focused our studies on hsa-miR-486-3p by demonstrating that
      MYB controls miR-486-3p expression through the transactivation of its host gene,
      ankyrin-1 (ANK1) and that miR-486-3p affects HPCs commitment. Indeed,
      overexpression and knockdown experiments demonstrated that miR-486-3p supports
      the erythropoiesis while restraining the megakaryopoiesis. Of note, miR-486-3p
      also favors granulocyte differentiation while repressing the macrophage
      differentiation. To shed some light on the molecular mechanisms through which miR
      486-3p affects HPCs lineage commitment, we profiled the gene expression changes
      upon miR-486-3p overexpression in CD34+ cells. Among the genes downregulated in
      miR-486-3p-overexpressing HPCs and computationally predicted to be miR-486-3p
      targets, we identified MAF as a miR-486-3p target by 3'UTR luciferase reporter
      assay. Noteworthy, MAF overexpression was able to partially reverse the effects
      of miR-486-3p overexpression on erythroid versus megakaryocyte lineage choice.
      Moreover, the MYB/MAF co-silencing constrained the skewing of erythroid versus
      megakaryocyte lineage commitment in MYB-silenced CD34+ cells, by restraining the
      expansion of megakaryocyte lineage while partially rescuing the impairment of
      erythropoiesis. Therefore, our data collectively demonstrate that MYB favors
      erythropoiesis and restrains megakaryopoiesis through the transactivation of miR
      486-3p expression and the subsequent downregulation of MAF. As a whole, our study
      uncovers the MYB/miR-486-3p/MAF axis as a new mechanism underlying the MYB-driven
      control of erythroid versus megakaryocyte lineage fate decision. 

PMID- 25857264
TI  - A novel autoregulatory loop between the Gcn2-Atf4 pathway and (L)-Proline
      [corrected] metabolism controls stem cell identity.
AB  - Increasing evidence indicates that metabolism is implicated in the control of
      stem cell identity. Here, we demonstrate that embryonic stem cell (ESC) behaviour
      relies on a feedback loop that involves the non-essential amino acid L-Proline (L
      Pro) in the modulation of the Gcn2-Eif2alpha-Atf4 amino acid starvation response
      (AAR) pathway that in turn regulates L-Pro biosynthesis. This regulatory loop
      generates a highly specific intrinsic shortage of L-Pro that restricts
      proliferation of tightly packed domed-like ESC colonies and safeguards ESC
      identity. Indeed, alleviation of this nutrient stress condition by exogenously
      provided L-Pro induces proliferation and modifies the ESC phenotypic and
      molecular identity towards that of mesenchymal-like, invasive pluripotent stem
      cells. Either pharmacological inhibition of the prolyl-tRNA synthetase by
      halofuginone or forced expression of Atf4 antagonises the effects of exogenous L
      Pro. Our data provide unprecedented evidence that L-Pro metabolism and the
      nutrient stress response are functionally integrated to maintain ESC identity. 

PMID- 25857265
TI  - The tumor-modulatory effects of Caspase-2 and Pidd1 do not require the scaffold
      protein Raidd.
AB  - The receptor-interacting protein-associated ICH-1/CED-3 homologous protein with a
      death domain (RAIDD/CRADD) functions as a dual adaptor and is a constituent of
      different multi-protein complexes implicated in the regulation of inflammation
      and cell death. Within the PIDDosome complex, RAIDD connects the cell death
      related protease, Caspase-2, with the p53-induced protein with a death domain 1
      (PIDD1). As such, RAIDD has been implicated in DNA-damage-induced apoptosis as
      well as in tumorigenesis. As loss of Caspase-2 leads to an acceleration of tumor
      onset in the EMU-Myc mouse lymphoma model, whereas loss of Pidd1 actually delays
      onset of this disease, we set out to interrogate the role of Raidd in cancer in
      more detail. Our data obtained analyzing EMU-Myc/Raidd(-/-) mice indicate that
      Raidd is unable to protect from c-Myc-driven lymphomagenesis. Similarly, we
      failed to observe a modulatory effect of Raidd deficiency on DNA-damage-driven
      cancer. The role of Caspase-2 as a tumor suppressor and that of Pidd1 as a tumor
      promoter can therefore be uncoupled from their ability to interact with the Raidd
      scaffold, pointing toward the existence of alternative signaling modules engaging
      these two proteins in this context. 

PMID- 25857267
TI  - Sufficient catheter length for pneumothorax needle decompression: a meta
      analysis.
AB  - INTRODUCTION: Needle thoracostomy is the prehospital treatment for tension
      pneumothorax. Sufficient catheter length is necessary for procedural success. The
      authors of this study determined minimum catheter length needed for procedural
      success on a percentile basis. METHODS: A meta-analysis of existing studies was
      conducted. A Medline search was performed using the search terms: needle
      decompression, needle thoracentesis, chest decompression, pneumothorax
      decompression, needle thoracostomy, and tension pneumothorax. Studies were
      included if they published a sample size, mean chest wall thickness, and a
      standard deviation or confidence interval. A PubMed search was performed in a
      similar fashion. Sample size, mean chest wall thickness, and standard deviation
      were found or calculated for each study. Data were combined to create a pooled
      dataset. Normal distribution of data was assumed. Procedural success was defined
      as catheter length being equal to or greater than the chest wall thickness.
      RESULTS: The Medline and PubMed searches yielded 773 unique studies; all study
      abstracts were reviewed for possible inclusion. Eighteen papers were identified
      for full manuscript review. Thirteen studies met all inclusion criteria and were
      included in the analysis. Pooled sample statistics were: n=2,558; mean=4.19 cm;
      and SD=1.37 cm. Minimum catheter length needed for success at the 95th percentile
      for chest wall size was found to be 6.44 cm. DISCUSSION: A catheter of at least
      6.44 cm in length would be required to ensure that 95% of the patients in this
      pooled sample would have penetration of the pleural space at the site of needle
      decompression, and therefore, a successful procedure. These findings represent
      Level III evidence.

PMID- 25857266
TI  - Pontin, a new mutant p53-binding protein, promotes gain-of-function of mutant
      p53.
AB  - Tumor-suppressor p53 is frequently mutated in human cancers. Many tumor
      associated mutant p53 (mutp53) proteins gain new functions in promoting
      tumorigenesis, defined as gain-of-function (GOF). The mechanisms for mutp53 GOF
      are not well understood. Here, we report Pontin, a highly conserved AAA+ ATPase
      important for various cellular functions, as a new mutp53-binding protein. This
      Pontin-mutp53 interaction promotes mutp53 GOF in invasion, migration and
      anchorage-independent growth of tumor cells. The ATPase domain of Pontin is
      crucial for its promoting effect on mutp53 GOF; blocking the ATPase activity of
      Pontin by a Pontin-specific ATPase inhibitor or an ATPase-deficient dominant
      negative Pontin expression vector greatly diminished mutp53 GOF. Pontin promotes
      mutp53 GOF through regulation of mutp53 transcriptional activity; knockdown of
      Pontin abolished the transcriptional regulation of mutp53 toward a group of
      genes. Furthermore, overexpression of Pontin in tumors is associated with the
      poor survival in cancer patients, especially those containing mutp53. Our results
      highlight an important role and mechanism for Pontin, a new mutp53 partner, in
      promoting mutp53 GOF in tumorigenesis. 

PMID- 25857268
TI  - Evaluation of the enantioselective binding of imazalil to human serum albumin by
      capillary electrophoresis.
AB  - In this work, a methodology for the evaluation of enantioselective binding of
      imazalil (IMA) enantiomers to human serum albumin (HSA) that does not require the
      separation of free and bound to HSA fractions is developed. This methodology
      comprises the incubation of IMA-HSA designed mixtures for 30 min directly in the
      capillary electrophoresis system and the subsequent direct injection and chiral
      separation of IMA employing highly sulfated beta-cyclodextrin as chiral selector
      and the complete filling technique. Two mathematical approaches were used to
      estimate apparent affinity constants (K1), protein binding and enantioselectivity
      (ES) for both enantiomers of IMA. Moderate enantioselective binding of IMA
      enantiomers to HSA (ES = 2.0) was shown by the 1:1 stoichiometry and log K1
      values of 3.4 +/- 0.4 and 3.1 +/- 0.3 for the first and second eluted
      enantiomers, respectively.

PMID- 25857270
TI  - The renaissance era of peptides in drug discovery at the 14th Naples workshop on
      bioactive peptides.

PMID- 25857269
TI  - Doxorubicin resistance in breast cancer is driven by light at night-induced
      disruption of the circadian melatonin signal.
AB  - Chemotherapeutic resistance, particularly to doxorubicin (Dox), represents a
      major impediment to successfully treating breast cancer and is linked to elevated
      tumor metabolism and tumor over-expression and/or activation of various families
      of receptor- and non-receptor-associated tyrosine kinases. Disruption of
      circadian time structure and suppression of nocturnal melatonin production by dim
      light exposure at night (dLEN), as occurs with shift work, and/or disturbed sleep
      wake cycles, is associated with a significantly increased risk of an array of
      diseases, including breast cancer. Melatonin inhibits human breast cancer growth
      via mechanisms that include the suppression of tumor metabolism and inhibition of
      expression or phospho-activation of the receptor kinases AKT and ERK1/2 and
      various other kinases and transcription factors. We demonstrate in tissue
      isolated estrogen receptor alpha-positive (ERalpha+) MCF-7 human breast cancer
      xenografts, grown in nude rats maintained on a light/dark cycle of LD 12:12 in
      which dLEN is present during the dark phase (suppressed endogenous nocturnal
      melatonin), a significant shortening of tumor latency-to-onset, increased tumor
      metabolism and growth, and complete intrinsic resistance to Dox therapy.
      Conversely, a LD 12:12 dLEN environment incorporating nocturnal melatonin
      replacement resulted in significantly lengthened tumor latency-to-onset, tumor
      regression, suppression of nighttime tumor metabolism, and kinase and
      transcription factor phosphorylation, while Dox sensitivity was completely
      restored. Melatonin acts as both a tumor metabolic inhibitor and circadian
      regulated kinase inhibitor to reestablish the sensitivity of breast tumors to Dox
      and drive tumor regression, indicating that dLEN-induced circadian disruption of
      nocturnal melatonin production contributes to a complete loss of tumor
      sensitivity to Dox chemotherapy. 

PMID- 25857272
TI  - Experimental investigation into the interaction between the human body and room
      airflow and its effect on thermal comfort under stratum ventilation.
AB  - Room occupants' comfort and health are affected by the airflow. Nevertheless,
      they themselves also play an important role in indoor air distribution. This
      study investigated the interaction between the human body and room airflow under
      stratum ventilation. Simplified thermal manikin was employed to effectively
      resemble the human body as a flow obstacle and/or free convective heat source.
      Unheated and heated manikins were designed to fully evaluate the impact of the
      manikin at various airflow rates. Additionally, subjective human tests were
      conducted to evaluate thermal comfort for the occupants in two rows. The findings
      show that the manikin formed a local blockage effect, but the supply airflow
      could flow over it. With the body heat from the manikin, the air jet penetrated
      farther compared with that for the unheated manikin. The temperature downstream
      of the manikin was also higher because of the convective effect. Elevating the
      supply airflow rate from 7 to 15 air changes per hour varied the downstream
      airflow pattern dramatically, from an uprising flow induced by body heat to a jet
      dominated flow. Subjective assessments indicated that stratum ventilation
      provided thermal comfort for the occupants in both rows. Therefore, stratum
      ventilation could be applied in rooms with occupants in multiple rows. 

PMID- 25857271
TI  - Serum proprotein convertase subtilisin/kexin type 9 concentration is not
      increased by plant stanol ester consumption in normo- to moderately
      hypercholesterolaemic non-obese subjects. The BLOOD FLOW intervention study.
AB  - Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates low-density
      lipoprotein (LDL) cholesterol (LDL-C) metabolism by targeting LDL receptors for
      degradation. Statins increase serum PCSK9 concentration limiting the potential of
      statins to reduce LDL-C, whereas ezetimibe, inhibitor of cholesterol absorption,
      has ambiguous effects on circulating PCSK9 levels. Plant stanols also reduce
      cholesterol absorption, but their effect on serum PCSK9 concentration is not
      known. Therefore, we performed a controlled, randomized, double-blind study, in
      which 92 normo- to moderately hypercholesterolaemic subjects (35 males and 57
      females) consumed vegetable-oil spread 20 g/day enriched (plant stanol group,
      n=46) or not (control group, n=46) with plant stanols 3 g/day as ester for 6
      months. Fasting blood samples were drawn at baseline and at the end of the study.
      Serum PCSK9 concentration was analysed with Quantikine Elisa Immunoassay, serum
      and lipoprotein lipids enzymatically and serum non-cholesterol sterols with GLC.
      At baseline, PCSK9 concentration varied from 91 to 716 ng/ml with a mean value of
      278+/-11 (S.E.M.) ng/ml with no gender difference. It correlated with serum and
      LDL-C, serum triglycerides, age, body mass index (BMI) and plasma glucose
      concentration, but not with variables of cholesterol metabolism when adjusted to
      serum cholesterol. Plant stanols reduced LDL-C by 10% from controls (P<0.05), but
      PCSK9 levels were unchanged and did not differ between the groups. In conclusion,
      the present study demonstrated for the first time that inhibition of cholesterol
      absorption with plant stanol esters did not affect serum PCSK9 concentration.
      Thus, plant stanol esters provide an efficient dietary means to lower LDL-C
      without interfering with the PCSK9 metabolism and in this regard the LDL receptor
      mediated cellular cholesterol uptake and removal. 

PMID- 25857273
TI  - Some South African Rubiaceae Tree Leaf Extracts Have Antimycobacterial Activity
      Against Pathogenic and Non-pathogenic Mycobacterium Species.
AB  - Tuberculosis (TB) caused by Mycobacterium tuberculosis remains an ongoing threat
      to human health. Many plant species contain antimycobacterial compounds, which
      may serve as template molecules for new anti-TB drugs. The Rubiaceae family is
      the largest family of trees in southern Africa, and preliminary evidence revealed
      antimycobacterial activity in several species of the genus, motivating further
      studies. Leaf extracts of 15 tree species from the Rubiaceae family were screened
      for antimycobacterial activity against pathogenic M. tuberculosis and non
      pathogenic Mycobacterium smegmatis, Mycobacterium aurum and Mycobacterium bovis
      BCG (Bacillus Calmette-Guerin) using a twofold serial microdilution assay.
      Cytotoxicity was determined using a tetrazolium-based colorimetric assay against
      C3A liver cells and Vero kidney cells. Minimum inhibitory concentration values as
      low as 0.04 mg/mL against M. smegmatis and M. tuberculosis were recorded.
      Activity against M. aurum was the best predictor of activity against pathogenic
      M. tuberculosis (correlation coefficient = 0.9). Bioautography indicated at least
      40 different antimycobacterial compounds in the extracts. Cytotoxicity of the
      extracts varied, and Oxyanthus speciosus had the most promising selectivity index
      values.

PMID- 25857274
TI  - A multiscale approach for modeling actuation response of polymeric artificial
      muscles.
AB  - Artificial muscles are emerging materials in the field of smart materials with
      applications in aerospace, robotic, and biomedical industries. Despite extensive
      experimental investigations in this field, there is a need for numerical modeling
      techniques that facilitate cutting edge research and development. This work aims
      at studying an artificial muscle made of twisted Nylon 6.6 fibers that are highly
      cold-drawn. A computationally efficient phenomenological thermo-mechanical
      constitutive model is developed in which several physical properties of the
      artificial muscles are incorporated to minimize the trial-and-error numerical
      curve fitting processes. Two types of molecular chains are considered at the
      micro-scale level that control training and actuation processes viz. (a)
      helically oriented chains which are structural switches that store a twisted
      shape in their low temperature phase and restore their random configuration
      during the thermal actuation process, and (b) entropic chains which are highly
      drawn chains that could actuate as soon as the muscle heats up, and saturates
      when coil contact temperature is reached. The thermal actuation response of the
      muscle over working temperatures has been elaborated in the Modeling section. The
      performance of the model is validated by available experiments in the literature.
      The model may provide a design platform for future artificial muscle
      developments. 

PMID- 25857275
TI  - Proteomic study on the effects of silver nanoparticles on soybean under flooding
      stress.
AB  - Flooding negatively affects the soybean growth; however, silver nanoparticles
      (AgNPs) enhanced the growth under stress. To study the effects of AgNPs on
      soybean under flooding, a gel-free proteomic technique was used. The
      morphological analysis of early-stage soybean exposed to flooding with AgNPs of
      various sizes and concentrations revealed enhanced seedling growth by treatment
      with 15n m AgNPs at 2 ppm. Differentially changed 107 root proteins were
      predominantly associated with stress, signaling, and cell metabolism.
      Hierarchical clustering divided these proteins into 3 clusters. Based on cluster
      analysis, the abundances of glyoxalase II 3 and fermentation related proteins
      were time-dependently increased under flooding stress, but decreased in response
      to AgNPs. Six enzymes involved in metabolic pathways were analyzed at the
      transcriptional level. The alcohol dehydrogenase 1 and pyruvate decarboxylase 2
      genes were up-regulated under flooding stress while down-regulated in response to
      AgNPs. Moreover, comparatively low transcript level of glyoxalase II 3 under
      AgNPs treatment implies that less cytotoxic by-products of glycolysis are
      produced in AgNPs exposed soybeans as compared to flooded soybean. These results
      suggest that the AgNPs treated soybeans might have experienced less oxygen
      deprivation stress, which might be the key factor for better growth performance
      of AgNPs treated soybeans under flooding stress. BIOLOGICAL SIGNIFICANCE: This
      study highlighted the effect of silver nanoparticles (AgNPs) on the soybean under
      flooding stress. Silver nanoparticles (2 ppm AgNPs, 15 nm in size) treatment
      facilitate the soybean under flooding stress enhancing seedling growth. A time
      course comparative gel-free proteomic study was performed to analyze the changes
      inproteome profiles in response to AgNPs treatment under flooding. The 107
      differentially changed root proteins were predominantly associated with stress,
      signaling, cell metabolism. The abundances of the glyoxalase II 3 and
      fermentation related proteins were significantly increased on exposure to
      flooding; however, decreased by AgNPs treatment. Comparatively low transcript
      level of glyoxalase II 3 under AgNPs treatment implies that less cytotoxic by
      products of glycolysis are produced in AgNPs exposed soybeans as compared to
      flooded soybean. Moreover, the observed up-regulation of the alcohol
      dehydrogenase 1 and pyruvate decarboxylase 2 genes under flooding stress
      condition and its down-regulation in response to AgNPs treatment might be related
      to a metabolic shift towards normal cellular processes.

PMID- 25857276
TI  - Basal and exercise induced label-free quantitative protein profiling of m. vastus
      lateralis in trained and untrained individuals.
AB  - Morphological and metabolic adaptations of the human skeletal muscle to exercise
      are crucial to improve performance and prevent chronic diseases and metabolic
      disorders. In this study we investigated human skeletal muscle protein
      composition in endurance trained (ET) versus untrained individuals (UT) and its
      modulation by an acute bout of endurance exercise. Participants were recruited
      based on their VO2max and subjected to a bicycle exercise test. M. vastus
      lateralis biopsies were taken before and three hours after exercise. Muscle
      lysates were analyzed using off-gel LC-MS/MS. Relative protein abundances were
      compared between ET and UT at rest and after exercise. Comparing UT and ET, we
      identified 92 significantly changed proteins under resting conditions.
      Specifically, fiber-type-specific and proteins of the oxidative phosphorylation
      and tricarboxylic acid cycle were increased in ET. In response to acute exercise,
      71 proteins in ET and 44 in UT were altered. Here, a decrease of proteins
      involved in energy metabolism accompanied with alterations of heat shock and
      proteasomal proteins could be observed. In summary, long-term endurance training
      increased the basal level of structural and mitochondrial proteins in skeletal
      muscle. In contrast, acute exercise resulted in a depletion of proteins related
      to substrate utilization, especially in trained athletes. BIOLOGICAL
      SIGNIFICANCE: The investigation of the human skeletal muscle proteome in response
      to exercise may provide novel insights into the process of muscular plasticity.
      It is of importance in the development of exercise-based strategies in the
      prevention and therapy of many chronic inflammatory and degenerative diseases
      which are often accompanied by muscular deconditioning. Up to date, proteomic
      investigations of the human muscle proteome in adaptation to exercise are mainly
      focused on untrained individuals and often restricted to animal studies. In the
      present study we compare the protein composition in endurance trained athletes
      and untrained individuals in the resting muscle and its modulation in response to
      acute exercise. To our knowledge, we present the first comprehensive analysis of
      skeletal muscle proteome alterations in response to acute and long-term exercise
      intervention.

PMID- 25857277
TI  - Tackling proteome changes in the longissimus thoracis bovine muscle in response
      to pre-slaughter stress.
AB  - Pre-slaughter stress has adverse effects on meat quality that can lead to the
      occurrence of Dark Firm Dry (DFD) meat in cattle. This study explores the
      previously uncharacterized proteome changes linked to pre-slaughter stress in the
      longissimus thoracis (LT) bovine muscle. Differential proteome profiles of DFD
      and normal (non-DFD) LT meat samples from male calves of the Rubia Gallega breed
      were assessed by 2-DE coupled to MS analysis (LC-MS/MS and MALDI TOF/TOF MS). A
      total of seven structural-contractile proteins (three different myosin light
      chain isoforms, two fast skeletal myosin light chain 2 isoforms, troponin C type
      2 and cofilin-2) and three metabolism enzymes (triosephosphate isomerase, ATP
      synthase and beta-galactoside alpha-2,6-sialyltransferase) were found to have
      statistically significant differential abundance in sample groups. In addition, 2
      DE in combination with the phosphoprotein-specific fluorescent dye Pro-Q DPS
      revealed that highly phosphorylated fast skeletal myosin regulatory light chain 2
      isoforms underwent the most intense relative change in muscle conversion to DFD
      meat. Therefore, they appear to be the most sensitive biomarkers of stress just
      prior to slaughter in Rubia Gallega. Overall, these findings will facilitate a
      more integrative understanding of the biochemical processes associated with
      stress in cattle muscle and their effects in meat quality. BIOLOGICAL
      SIGNIFICANCE: Pre-slaughter stress is a crucial factor in meat production.
      Animals destined for slaughter are stressed by a variety of endogenous and
      exogenous factors that negatively affect the complex post-mortem biochemical
      events underlying the conversion of muscle into meat. The study of the muscle
      proteome has a great relevance for understanding the molecular mechanisms
      associated with stress. However, there is no information available on the
      molecular changes linked to pre-slaughter stress in cattle on the proteome scale.
      Our study led to the identification of a number of candidate proteins associated
      with the response to pre-slaughter stress in the LT bovine muscle of the Rubia
      Gallega breed. The functions of those significantly changed proteins have a clear
      biological relationship with stress response. These findings contribute to a
      deeper insight into the molecular pathways that respond to stress in cattle.

PMID- 25857278
TI  - Human monocyte-derived macrophages are heterogenous: Proteomic profile of
      different phenotypes.
AB  - Tissue macrophages play a key role in many aspects of human physiology and
      pathology. These cells are heterogeneous both in term of morphology and function.
      As an example, heterogeneity has been reported within the atherosclerotic lesions
      where distinct populations exert opposite functions driving plaque progression or
      stability. Tissue macrophages are not easily obtained and differentiated blood
      derived monocytes are largely used as surrogate model. We previously reported
      that human macrophages spontaneously differentiated from adherent monocytes show
      two dominant subsets, distinct for morphology (spindle and round) and functions.
      The aim of this study was to evaluate the intracellular proteome of these two
      macrophage subsets by means of a microproteomic workflow properly set up to
      simultaneously identify and quantify proteins from a minimal number of
      morphotypically heterogeneous cells in culture. We report two distinct proteomic
      profiles that distinguish round from spindle macrophages. In particular,
      differential abundances were observed for proteins involved in membrane traffic
      regulation, lipid handling, efferocytosis, and protection against stress
      conditions. Results reinforce and extend previous data on the functional and
      antigenic profile of these macrophage phenotypes strengthening the suitability of
      our model to focus on macrophage heterogeneity. BIOLOGICAL SIGNIFICANCE: Tissue
      macrophages patrol homeostatic functions, immune surveillance, and resolution of
      inflammation. The spectrum of macrophage activation states is, therefore, wide
      and gives ground for the heterogeneity of these cells, documented in health and
      disease. This study provides knowledge of the distinct proteome that
      characterises the two dominant morphotypes (round and spindle) of human
      macrophages that, in our culture condition, are generated by spontaneous
      differentiation from blood-derived monocytes. Results extend previous data about
      the different antigenic, transcriptional, and functional profiles of these
      morphotypes and further strengthen the suitability of this in vitro model to
      study macrophage heterogeneity and to address the effects of environmental
      challenges and drugs.

PMID- 25857279
TI  - In-depth proteomic analysis of nacre, prism, and myostracum of Mytilus shell.
AB  - Mytilus is an economically important bivalve and its shell is a biomineralized
      tissue with various microstructures/layers. In the present study, the shell of
      marine mussel, Mytilus coruscus, was analyzed and three shell layers with
      different morphologies and polymorphs were observed, which includes nacre,
      fibrous prism, and myostracum strongly attached by adductor muscles to the
      interior of the shell surface. In order to understand whether these different
      shell layers contain different shell matrix proteins (SMPs), the transcriptome
      sequencing of M. coruscus mantle and a parallel proteomic analysis of SMPs in the
      three shell layers were performed. A combination of LC-MS/MS analysis with the
      mantle transcriptome dataset search resulted in the identification of a total of
      63 proteins from M. coruscus shell. From this protein set, fifteen, fourteen, and
      eight proteins were found to be unique to nacre, fibrous prism, and myostracum
      layers, respectively. In addition, many novel shell proteins were also
      identified. The data in this study could be used as a background to explore the
      roles of SMPs in the deposition of different shell layers (nacre vs. fibrous
      prism vs. myostracum), the different polymorphisms of calcium carbonate
      (aragonite vs. calcite); and further, the identified proteins from the myostracum
      could provide candidates for studying the mechanism of adductor muscle-shell
      attachment. BIOLOGICAL SIGNIFICANCE: In this paper, we characterized for the
      first time the protein set from different shell layers in Mytilus. Shell matrix
      proteins are the major component that controls different aspects of the shell
      formation process and thus a source of bioactive molecules that would offer
      interesting perspectives in biomaterials and biomedical fields. Our data can be
      used as a resource for further exploring the roles of shell matrix proteins in
      the deposition of different shell layers (nacre vs. fibrous prism vs. myostracum)
      or different polymorphisms of calcium carbonate (aragonite vs. calcite), and the
      identified protein set of myostracum provided candidates for studying the
      mechanism of adductor muscle-shell attachment.

PMID- 25857280
TI  - The role of depressive symptomatology in peri- and post-menopause.
AB  - OBJECTIVES: There is evidence that menopausal symptoms manifested at peri
      menopause occur less frequently when compared to the symptoms experienced at post
      menopause. The aim of this study was to investigate this and to test the
      hypothesis that depressive symptomatology mediates the relationship between
      menopausal stage and symptom frequency. METHODS: This cross-sectional study
      included 213 women (M age=52 years), of whom 125 were peri- and 88 post
      menopausal. Measures comprised the Center for Epidemiologic Studies-Depression
      scale (CES-D) and the Women's Health Questionnaire (WHQ) vasomotor symptoms and
      somatic symptoms subscales. RESULTS: Multiple mediated regression analyses
      provided evidence that somatic symptoms and vasomotor symptoms were less frequent
      at post- compared to peri-menopause, and that these differences were mediated by
      depressive symptomatology. Multivariate effect sizes ranged from small to
      moderate, and univariate effect sizes were uniformly small with wide confidence
      intervals. CONCLUSIONS: The frequency of vasomotor and somatic symptoms appears
      to increase with depressed affect. The management of symptoms could include
      interventions of a psychotherapeutic nature, which may offset this effect,
      particularly in women for whom depressive symptoms are a feature of the
      climacteric syndrome. The extent to which depression and the climacteric syndrome
      may be causally related to one another remains unclear and longitudinal research
      should further examine the mechanisms of this association.

PMID- 25857281
TI  - Zwitterionic supramolecular nanoparticles: self-assembly and responsive
      properties.
AB  - Supramolecular nanoparticles (SNPs) are of high interest in both nanoscience and
      molecular diagnostics and therapeutics, because of their reversible and
      designable properties. To ensure colloidal stabilization and biocompatibility,
      most reported strategies require the use of hydrophilic long-chain polymers such
      as poly(ethylene glycol). Here, we show the formation of zwitterionic
      supramolecular nanoparticles (ZSNPs) from appropriately functionalized mono- and
      multivalent components, based on the hetero-ternary host-guest complexation
      between cucurbit[8]uril (CB[8]), methyl viologen (MV), and azobenzene (Azo),
      while using the monovalent, small-molecule, non-fouling Azo-carboxybetaine analog
      (Azo-Zwit) as the shell-forming component. Even though steric shell stabilization
      is absent, the zwitterionic Azo-Zwit ensures stability of the ZSNPs in water, in
      PBS (pH 7.4) at ionic strengths ranging from 0-700 mM, and in PBS containing BSA.
      Size tuning by control over the stoichiometry of the components, as well as
      reversible assembly and disassembly by photoisomerization of the Azo moieties
      were observed. Surprisingly, the ZSNPs exhibited aggregation at the narrow pH
      range of 6.2-6.8. 

PMID- 25857282
TI  - Secondary bone grafting with simultaneous auto-tooth transplantation to the
      alveolar cleft.
AB  - One of the most important purposes of secondary bone grafting of the alveolar
      cleft is to stabilize the maxillary alveolar arch with completion of the dental
      arch. We report a case of secondary bone grafting with simultaneous auto-tooth
      transplantation to the alveolar cleft, using particulate cancellous bone and
      marrow (PCBM) combined with platelet-rich plasma (PRP), which contains many
      growth factors. The patient was born with a bilateral cleft lip and left buccal
      localized cleft alveolus. We performed bone grafting to the cleft using PCBM with
      PRP and transplantation of the supernumerary tooth under general anesthesia when
      the patient was aged 11 years, 10 months. The postoperative course was uneventful
      and without any complications. The orthodontic treatment was nearly complete 10
      months after the operation. The transplanted tooth was stable, and a normal
      gingival contour was attained during the 2-year follow-up period. The case was
      successful in achieving a stable occlusal condition within a short period. We
      suggest secondary bone grafting with simultaneous auto-tooth transplantation as
      an option for alveolar cleft treatment. 

PMID- 25857283
TI  - Bilateral Sagittal Split Ramus Osteotomy Versus Distraction Osteogenesis for
      Advancement of the Retrognathic Mandible.
AB  - PURPOSE: The aim of the present study was to identify significant differences in
      skeletal stability and neurosensory disturbance (NSD) of the inferior alveolar
      nerve (IAN) between bilateral sagittal split ramus osteotomy (BSSO) and
      distraction osteogenesis (DO) for mandibular advancement surgery. MATERIALS AND
      METHODS: We performed a systematic and electronic search of several databases
      using specific keywords, a reference search, and a manual search through November
      2014. The inclusion criteria were clinical human studies, including randomized
      controlled trials (RCTs), controlled clinical trials (CCTs), and retrospective
      studies, with the aim of comparing BSSO and DO (predictor variables) after
      mandibular advancement surgery with regard to skeletal stability and NSD of the
      IAN (outcome variables). Both linear and angular measurements of the horizontal
      and vertical positions of the mandible were analyzed. For binary outcomes, we
      calculated a standard estimation of the risk ratio using the random-effects model
      if heterogeneity was detected; otherwise, a fixed effects model, with a 95%
      confidence interval (CI), was used. Weighted mean differences or standard mean
      differences were used to construct forest plots of continuous data. In addition,
      the number needed to treat, with the 95% CIs, was calculated for NSD of the IAN.
      RESULTS: Our initial PubMed search identified 215 studies, of which 9 met our
      inclusion criteria-3 RCTs, 1 CCT, and 5 retrospective studies. No statistically
      significant difference was found between the 2 groups regarding skeletal
      stability in either the vertical (P = .34) or horizontal (P = .88) direction. A
      statistically significant difference was found between BSSO and DO with regard to
      NSD of IAN function (P = .004). CONCLUSION: The results of the present meta
      analysis have shown that DO significantly reduced the incidence of NSD of the IAN
      after lengthening of the retrognathic mandible compared with the BBSO.

PMID- 25857284
TI  - Autoprocessing of neutrophil elastase near its active site reduces the efficiency
      of natural and synthetic elastase inhibitors.
AB  - An imbalance between neutrophil-derived proteases and extracellular inhibitors is
      widely regarded as an important pathogenic mechanism for lung injury. Despite
      intense efforts over the last three decades, attempts to develop small-molecule
      inhibitors for neutrophil elastase have failed in the clinic. Here we discover an
      intrinsic self-cleaving property of mouse neutrophil elastase that interferes
      with the action of elastase inhibitors. We show that conversion of the single
      chain (sc) into a two-chain (tc) neutrophil elastase by self-cleavage near its S1
      pocket altered substrate activity and impaired both inhibition by endogenous
      alpha-1-antitrypsin and synthetic small molecules. Our data indicate that
      autoconversion of neutrophil elastase decreases the inhibitory efficacy of
      natural alpha-1-antitrypsin and small-molecule inhibitors, while retaining its
      pathological potential in an experimental mouse model. The so-far overlooked
      occurrence and properties of a naturally occurring tc-form of neutrophil elastase
      necessitates the redesign of small-molecule inhibitors that target the sc-form as
      well as the tc-form of neutrophil elastase. 

PMID- 25857285
TI  - Effects of dietary protease on nitrogen emissions from broiler production: a
      holistic comparison using Life Cycle Assessment.
AB  - BACKGROUND: The aim of the study was to quantify the effects of the use of a
      protease Ronozyme(r) ProAct in broiler feed on the environmental impacts of
      broiler and broiler feed production chains. This was done by using a Life Cycle
      Assessment (LCA) modelling approach with data from trials using both standard
      soya-based broiler diets and reduced-protein diets with added protease. RESULTS:
      The results for the feed production chain showed that there was a reduction in
      all environmental impact categories when protease was used in the diets. The
      biggest reduction occurred in the category of Global Warming Potential, mainly as
      a result of decreased carbon dioxide emissions from land use changes related to
      soya production. In the results for the broiler production chain, there were
      relatively bigger reductions in Eutrophication Potential and especially in
      Acidification Potential, mainly as a result of reduced feed protein content and
      subsequent nitrogen emissions from housing and manure management. CONCLUSION: The
      use of protease in the broiler diets reduced the environmental impacts of both
      feed production and broiler production. The latter is mainly through reduced
      ammonia emissions, which has substantial benefit per se in the poultry industry.

PMID- 25857286
TI  - A metal-organic framework constructed using a flexible tripodal ligand and
      tetranuclear copper cluster for sensing small molecules.
AB  - A new porous metal-organic framework (MOF) {[Cu4(OH)2(tci)2(bpy)2].11H2O} (1)
      based on a tetranuclear copper cluster with intracluster antiferromagnetic
      interactions was synthesized. Quartz crystal microbalance (QCM) sensor studies
      reveal sensitive and selective sensing for small molecules. 

PMID- 25857288
TI  - Fluorescence triggering: A general strategy for enumerating and phenotyping
      extracellular vesicles by flow cytometry.
AB  - Plasma contains cell-derived extracellular vesicles (EVs) which participate in
      various physiopathological processes and have potential biomedical applications.
      Despite intense research activity, knowledge on EVs is limited mainly due to the
      difficulty of isolating and characterizing sub-micrometer particles like EVs. We
      have recently reported that a simple flow cytometry (FCM) approach based on
      triggering the detection on a fluorescence signal enabled the detection of 50*
      more Annexin-A5 binding EVs (Anx5+ EVs) in plasma than the conventional FCM
      approach based on light scattering triggering. Here, we present the application
      of the fluorescence triggering approach to the enumeration and phenotyping of EVs
      from platelet free plasma (PFP), focusing on CD41+ and CD235a+ EVs, as well as
      their sub-populations which bind or do not bind Anx5. Higher EV concentrations
      were detected by fluorescence triggering as compared to light scattering
      triggering, namely 40* for Anx5+ EVs, 75* for CD41+ EVs, and 15* for CD235a+ EVs.
      We found that about 30% of Anx5+ EVs were of platelet origin while only 3% of
      them were of erythrocyte origin. In addition, a majority of EVs from platelet and
      erythrocyte origin do not expose PS, in contrast to the classical theory of EV
      formation. Furthermore, the same PFP samples were analyzed fresh and after freeze
      thawing, showing that freeze-thawing processes induce an increase, of about 35%,
      in the amount of Anx5+ EVs, while the other EV phenotypes remain unchanged. The
      method of EV detection and phenotyping by fluorescence triggering is simple,
      sensitive and reliable. We foresee that its application to EV studies will
      improve our understanding on the formation mechanisms and functions of EVs in
      health and disease and help the development of EV-based biomarkers.

PMID- 25857287
TI  - Hypoxia-inducible factors in cancer stem cells and inflammation.
AB  - Hypoxia-inducible factors (HIF) mediate metabolic switches in cells in hypoxic
      environments, including those in both normal and malignant tissues with limited
      supplies of oxygen. Paradoxically, recent studies have shown that cancer stem
      cells (CSCs) and activated immune effector cells exhibit high HIF activity in
      normoxic environments and that HIF activity is critical in the maintenance of
      CSCs as well as the differentiation and function of inflammatory cells. Given
      that inflammation and CSCs are two major barriers to effective cancer therapy,
      targeting HIF may provide a new approach to developing such treatments. 

PMID- 25857289
TI  - The impact of donor-acceptor phase separation on the charge carrier dynamics in
      pBTTT:PCBM photovoltaic blends.
AB  - The effect of donor-acceptor phase separation, controlled by the donor-acceptor
      mixing ratio, on the charge generation and recombination dynamics in pBTTT
      C14:PC70 BM bulk heterojunction photovoltaic blends is presented. Transient
      absorption (TA) spectroscopy spanning the dynamic range from pico- to
      microseconds in the visible and near-infrared spectral regions reveals that in a
      1:1 blend exciton dissociation is ultrafast; however, charges cannot entirely
      escape their mutual Coulomb attraction and thus predominantly recombine
      geminately on a sub-ns timescale. In contrast, a polymer:fullerene mixing ratio
      of 1:4 facilitates the formation of spatially separated, that is free, charges
      and reduces substantially the fraction of geminate charge recombination, in turn
      leading to much more efficient photovoltaic devices. This illustrates that
      spatially extended donor or acceptor domains are required for the separation of
      charges on an ultrafast timescale (<100 fs), indicating that they are not only
      important for efficient charge transport and extraction, but also critically
      influence the initial stages of free charge carrier formation.

PMID- 25857290
TI  - Understanding cellulose dissolution: energetics of interactions of ionic liquids
      and cellobiose revealed by solution microcalorimetry.
AB  - In this report, the interactions between fifteen selected ionic liquids (ILs) and
      cellobiose (CB) are examined by high-precision solution microcalorimetry. The
      heat of mixing (Deltamix H) of CB and ILs, or CB and IL/molecular solvent (MS)
      solutions, provides the first ever-published measure of the affinity of CB with
      ILs. Most importantly, we found that there is a very good correlation between the
      nature of the results found for Deltamix H(CB) and the solubility behavior of
      cellulose. This correlation suggests that Deltamix H(CB) offers a good estimate
      of the enthalpy of dissolution of cellulose even in solvents in which cellulose
      is insoluble. Therefore, the current findings open up new horizons for
      unravelling the intricacies of the thermodynamic factors accounting for the
      spontaneity of cellulose dissolution in ILs or IL/MS solutions. 

PMID- 25857291
TI  - Strategies for Avoiding Recommendations for Additional Imaging Through a
      Comprehensive Comparison With Prior Studies.
AB  - PURPOSE: To determine the frequency and characteristics of recommendations for
      additional imaging and/or intervention (RAIs) in abdominal CT and MRI
      interpretations that might be avoided through comprehensive comparison with all
      available prior examinations. METHODS: A total of 1,006 RAIs in abdominopelvic CT
      and MRI reports were retrospectively evaluated. Reports and images from each
      patient's prior imaging examinations, including those of all relevant body parts
      and modalities, were reviewed to determine if the RAI could have been avoided
      based on prior imaging. Frequency and characteristics of such "avoidable" RAIs
      were evaluated. RESULTS: A total of 41 of 1,006 (4.1%) RAIs were avoidable. The
      key prior examination that established the RAI as avoidable was a different
      modality in 53.7% (22 of 41) and on a different body area in 41.5% (17 of 41) of
      cases, including chest imaging in 31.7% (13 of 41). A total of 83.3% (5 of 6)
      adrenal RAIs, and 80.0% (4 of 5) liver RAIs were avoidable based on prior chest
      imaging. The key finding was present on the prior images but was not described in
      the report in 46.3% (19 of 41) of cases. A greater number of prior examinations
      were available in cases of avoidable RAIs (mean, 12.2 +/- 16.7) than in those of
      nonavoidable RAIs (mean, 5.7 +/- 9.5) (P < .001). CONCLUSIONS: A small fraction
      of RAIs can be avoided by performing a thorough evaluation of all prior imaging
      examinations, including different modalities and body parts. Nearly half of the
      key prior examinations did not report the finding, highlighting the importance of
      directly reviewing relevant images, particularly chest imaging for evaluation of
      indeterminate upper-abdominal findings. Configuration of PACS for optimized
      selection and display of relevant examination reports and images may facilitate
      such comparisons.

PMID- 25857292
TI  - Are the elements of the proposed ozone National Ambient Air Quality Standards
      informed by the best available science?
AB  - The United States Environmental Protection Agency (US EPA) issues National
      Ambient Air Quality Standards (NAAQS) for six criteria pollutants, including
      ozone. Each standard has four elements: an indicator, level, averaging time, and
      form. Ozone levels (i.e., air concentrations) alone in scientific studies are not
      directly comparable to the "level" element of the NAAQS because the standard
      considers the level in the context of its relation to the remaining elements.
      Failure to appreciate this has led to misunderstandings regarding NAAQS that
      would be health-protective. This can be seen with controlled human ozone exposure
      studies, which often involved small numbers of people exercising quasi
      continuously for a long duration at an intensity not common in the general
      population (and unlikely achievable by most sensitive individuals), under worst
      case exposure profiles. In addition, epidemiology studies have used different
      averaging times and have had methodological limitations that may have biased
      results. Such considerations can make it difficult to compare ozone levels and
      results across studies and to appropriately apply them in a NAAQS evaluation.
      Relating patterns and circumstances of exposure, and exposure measurements, to
      all elements of the NAAQS can be challenging, but if US EPA fully undertook this,
      it would be evident that available evidence does not indicate that proposed lower
      ozone standards would be more health protective than the current one. 

PMID- 25857293
TI  - Building scientific confidence in the development and evaluation of read-across.
AB  - Read-across is an alternative approach exploited to address information
      requirements for risk assessment and for regulatory programmes such as the
      European Union's REACH regulation. Whilst read-across approaches are accepted in
      principle, difficulties still remain in applying them consistently in practice.
      Recent work within Cefic LRI and ECETOC attempted to summarize the state-of-the
      art and identify some of the barriers to broader acceptance of read-across
      approaches to overcome these. Acceptance is undoubtedly thwarted partly by the
      lack of a systematic framework to characterize the read-across justification and
      identify the uncertainties particularly for complex regulatory endpoints such as
      repeated-dose toxicity or prenatal developmental toxicity. Efforts are underway
      by the European Chemical's Agency (ECHA) to develop a Read-Across Assessment
      Framework (RAAF) and private sector experts have also considered the development
      of a similar framework. At the same time, mechanistic chemical categories are
      being proposed which are underpinned by Adverse Outcome Pathways (AOPs).
      Currently such frameworks are only focusing on discrete organic substances,
      though the AOP approach could conceivably be applied to evaluate more complex
      substances such as mixtures. Here we summarize the deliberations of the Cefic LRI
      read-across team in characterizing scientific confidence in the development and
      evaluation of read-across. 

PMID- 25857294
TI  - Cardiolipin-cytochrome c complex: Switching cytochrome c from an electron
      transfer shuttle to a myoglobin- and a peroxidase-like heme-protein.
AB  - Cytochrome c (cytc) is a small heme-protein located in the space between the
      inner and the outer membrane of the mitochondrion that transfers electrons from
      cytc-reductase to cytc-oxidase. The hexa-coordinated heme-Fe atom of cytc
      displays a very low reactivity toward ligands and does not exhibit significant
      catalytic properties. However, upon cardiolipin (CL) binding, cytc achieves
      ligand binding and catalytic properties reminiscent of those of myoglobin and
      peroxidase. In particular, the peroxidase activity of the cardiolipin-cytochrome
      c complex (CL-cytc) is critical for the redistribution of CL from the inner to
      the outer mitochondrial membranes and is essential for the execution and
      completion of the apoptotic program. On the other hand, the capability of CL-cytc
      to bind NO and CO and the heme-Fe-based scavenging of reactive nitrogen and
      oxygen species may affect apoptosis. Here, the ligand binding and catalytic
      properties of CL-cytc are analyzed in parallel with those of CL-free cytc,
      myoglobin, and peroxidase to dissect the potential mechanisms of CL in modulating
      the pro- and anti-apoptotic actions of cytc.

PMID- 25857295
TI  - Interfering parameters in the determination of urinary globotriaosylceramide
      (Gb3) in patients with chronic kidney disease.
AB  - INTRODUCTION: Globotriaosylceramide (Gb3, CD77) represents a pivotal part of the
      cell membrane. Measuring the urinary Gb3 content can be used to screen patients
      with chronic kidney disease (CKD) for Fabry disease, a disorder caused by
      hampered Gb3 degradation. However, little is known about factors influencing
      urinary Gb3 excretion other than Fabry disease. The aim of the present study was
      to identify routine diagnostic parameters as predictors of urinary Gb3 excretion
      in patients with CKD. METHODS: Our study included 609 subjects with CKD stage I
      V. We analyzed the influence of age, gender, renal function, urinary cell content
      and chemical characteristics on urinary Gb3 concentrations (total Gb3, Gb3-24
      isoform, and Gb3-24:18 isoform ratio), determined by direct electrospray
      ionization mass spectrometry. RESULTS: In 609 subjects the median total urinary
      Gb3 was 233 ng/mg and the Gb3-24:18 isoform ratio was 1.2. Twenty-one patients,
      none of whom had Fabry disease, had a Gb3-24:18 isoform ratio >=2.3. Females
      excreted a higher total amount of Gb3, but the Gb3-24:18 isoform ratio was
      comparable to males. Renal function and age had no influence on total Gb3, Gb3
      isoforms or the ratio. Only a distinct load of bacteria and leukocytes was
      associated with an increased Gb3 excretion. Urinary leukocytes, erythrocytes,
      bacteria, or protein content did not affect the Gb3-24:18 isoform ratio.
      CONCLUSION: The Gb3-24:18 isoform ratio is unaffected by several potential
      influencing variables and may thus be applied for screening for Fabry disease in
      unselected cohorts of patients presenting with CKD.

PMID- 25857296
TI  - Association of advanced age with concentrations of uraemic toxins in CKD.
AB  - To our knowledge, there are no studies on advanced chronic kidney disease (CKD)
      analysing the impact of ageing on serum concentrations of uraemic toxins while
      adjusting for renal function. Knowledge of this feature, however, could influence
      prognostic assessment and therapeutic decision-making, e.g. about when to start
      dialysis or how intensive it should be. Indeed, the slowing down of metabolism
      with age may result in lower uraemic toxin concentrations, hence reducing their
      toxic effects. In this case, a later start of dialysis or less intensive dialysis
      may become justified in an already fragile population that might enjoy a better
      quality of life without a survival disadvantage with conservative treatment. We
      assessed the impact of advancing age on uraemic solute concentrations [blood,
      urea, nitrogen (BUN), uric acid, creatinine, asymmetric and symmetric
      dimethylarginine (ADMA and SDMA), beta2-microglobulin and a large array of
      protein-bound solutes] by matching 126 maintenance haemodialysis patients
      subdivided into two age-groups, younger vs. older (using the median as cut-off:
      72 years). Concentrations were compared after age stratification and were matched
      with patient and dialysis characteristics. In addition, 93 non-dialysed CKD
      patients (median as cut-off: 70 years), with a comparable average estimated
      glomerular filtration rate (eGFR) between younger and older age-groups, were
      analysed. In haemodialysis patients, carboxy-methyl-furanpropionic acid (CMPF)
      levels were markedly higher and BUN and uric acid borderline lower in the older
      age-group. All other solutes showed no difference. At multifactor analysis, the
      concentration of several uraemic toxins was associated with residual renal
      function and protein intake in the overall haemodialysis group and the younger
      group, but the association with most solutes, especially those protein-bound, was
      lost in the older age-group. No differences were found in non-dialysed CKD
      patients. It was concluded that in this CKD population concentrations of uraemic
      toxins did not change substantially with calendar age. 

PMID- 25857297
TI  - Efficiency of delivery observed treatment in hemodialysis patients: the example
      of the native vitamin D therapy.
AB  - INTRODUCTION: Adherence to therapy is a relevant challenge in chronic
      hemodialysis patients. The directly observed therapy (DOT) could be an effective
      method to increase adherence for specific therapies. We aimed to study the
      performance of DOT versus home medication. We follow the impact of providing
      native vitamin D directly by the nurse after a dialysis session on the 25
      hydroxyvitamin [25(OH)D] concentrations. METHODS: In this observational study, we
      included 38 dialysis patients treated by stable dosage of cholecalciferol. DOT
      was implemented in December 2010. We considered the concentrations of 25-OH
      vitamin D three times before (T1 = June 2010, T2 = July 2010 and T3 = September
      2010) and three times after the modification of prescription (T4 = February 2011,
      T5 = March 2011 and T6 = April 2011). RESULTS: Median age was 72 [62; 79] years
      and 48 % were diabetics. Mean body mass index was 26 +/- 5 kg/m(2) and median
      dialysis vintage was 20 [8; 46] months. The patients were compared to themselves.
      Before DOT, median concentrations of 25(OH)D were 27 (14-36), 23 (17-31), 31 (22
      38) ng/mL at T1, T2 and T3, respectively. When DOT was effective, the
      concentrations significantly increased to 34 (28-44), 35 (29-41), 39 (32-47)
      ng/mL at T4, T5 and T6, respectively. Before DOT, 19 patients (50 %) reached the
      target of 30 ng/mL. After DOT, 29 patients (76 %) reached the target
      concentration of 30 ng/mL. CONCLUSIONS: In hemodialysis patients, DOT is both
      simple and effective to increase the therapeutic impact to native vitamin D.

PMID- 25857298
TI  - The pan-PI3K inhibitor GDC-0941 activates canonical WNT signaling to confer
      resistance in TNBC cells: resistance reversal with WNT inhibitor.
AB  - The pan-PI3K inhibitors are one treatment option for triple-negative breast
      cancer (TNBC). However, this treatment is ineffective for unknown reasons. Here,
      we report that aberrant expression of wingless-type MMTV integration site family
      (WNT) and activated WNT signals, which crosstalk with the PI3K-AKT-mTOR signaling
      pathway through GSK3beta, plays the most critical role in resistance to pan-PI3K
      inhibitors in TNBC cells. GDC-0941 is a pan-PI3K inhibitor that activates the
      WNT/beta-catenin pathway in TNBC cells through stimulation of WNT secretion. GDC
      0941-triggered WNT/beta-catenin pathway activation was observed in MDA-MB-231 and
      HCC1937 cells, which are TNBC cell lines showing aberrant WNT/beta-catenin
      activation, and not in SKBR3 and MCF7 cells. This observation is further
      investigated in vivo. GDC-0941 exhibited minimal tumor inhibition in MDA-MB-231
      cells, but it significantly suppressed tumor growth in HER-positive SK-BR3 cells.
      In vivo mechanism study revealed the activation of WNT/beta-catenin pathway by
      GDC-0941. A synergistic effect was observed when combined treatment with GDC-0941
      and the WNT inhibitor LGK974 at low concentrations in MDA-MB-231 cells. These
      findings indicated that WNT pathway activation conferred resistance in TNBC cells
      treated with GDC-0941. This resistance may be further circumvented through
      combined treatment with pan-PI3K and WNT inhibitors. Future clinical trials of
      these two inhibitors are warranted. 

PMID- 25857299
TI  - Low spinophilin expression enhances aggressive biological behavior of breast
      cancer.
AB  - Spinophilin, a putative tumor suppressor gene, has been shown to be involved in
      the pathogenesis of certain types of cancer, but its role has never been
      systematically explored in breast cancer. In this study, we determined for the
      first time the expression pattern of spinophilin in human breast cancer molecular
      subtypes (n = 489) and correlated it with survival (n = 921). We stably reduced
      spinophilin expression in breast cancer cells and measured effects on cellular
      growth, apoptosis, anchorage-independent growth, migration, invasion and self
      renewal capacity in vitro and metastases formation in vivo. Microarray profiling
      was used to determine the most abundantly expressed genes in spinophilin-silenced
      breast cancer cells. Spinophilin expression was significantly lower in basal-like
      breast cancer (p<0.001) and an independent poor prognostic factor in breast
      cancer patients (hazard ratio = 1.93, 95% confidence interval: 1.24 -3.03; p =
      0.004) A reduction of spinophilin levels increased cellular growth in breast
      cancer cells (p<0.05), without influencing activation of apoptosis. Anchorage
      independent growth, migration and self-renewal capacity in vitro and metastatic
      potential in vivo were also significantly increased in spinophilin-silenced cells
      (p<0.05). Finally, we identified several differentially expressed genes in
      spinophilin-silenced cells. According to our data, low levels of spinophilin are
      associated with aggressive behavior of breast cancer. 

PMID- 25857300
TI  - Esophageal adenocarcinoma and obesity: peritumoral adipose tissue plays a role in
      lymph node invasion.
AB  - Obesity is associated with cancer risk in esophageal adenocarcinoma (EAC).
      Adipose tissue directly stimulates tumor progression independently from body mass
      index (BMI), but the mechanisms are not fully understood. We studied the
      morphological, histological and molecular characteristics of peritumoral and
      distal adipose tissue of 60 patients with EAC, to investigate whether depot
      specific differences affect tumor behavior. We observed that increased adipocyte
      size (a hallmark of obesity) was directly associated with leptin expression,
      angiogenesis (CD31) and lymphangiogenesis (podoplanin); however, these parameters
      were associated with nodal metastasis only in peritumoral but not distal adipose
      tissue of patients. We treated OE33 cells with conditioned media (CM) collected
      from cultured biopsies of adipose tissue and we observed increased mRNA levels of
      leptin and adiponectin receptors, as well as two key regulator genes of
      epithelial-to-mesenchymal transition (EMT): alpha-smooth muscle actin (alpha-SMA)
      and E-cadherin. This effect was greater in cells treated with CM from peritumoral
      adipose tissue of patients with nodal metastasis and was partially blunted by a
      leptin antagonist. Therefore, peritumoral adipose tissue may exert a direct
      effect on the progression of EAC by secreting depot-specific paracrine factors,
      and leptin is a key player in this crosstalk. 

PMID- 25857302
TI  - A hydrophobic adsorbent based on hierarchical porous polymers derived from
      morphologies of a biomineral.
AB  - The hierarchical porous structures of vinyl polymers, such as polystyrene (PSt)
      and poly(methyl methacrylate) (PMMA), were derived from morphologies of a
      biomineral through replication. The resultant PSt hierarchical structures showed
      enhanced adsorption properties of organic molecules as hydrophobic adsorbents in
      an aqueous medium. 

PMID- 25857301
TI  - Large oncosomes contain distinct protein cargo and represent a separate
      functional class of tumor-derived extracellular vesicles.
AB  - Large oncosomes (LO) are atypically large (1-10 um diameter) cancer-derived
      extracellular vesicles (EVs), originating from the shedding of membrane blebs and
      associated with advanced disease. We report that 25% of the proteins, identified
      by a quantitative proteomics analysis, are differentially represented in large
      and nano-sized EVs from prostate cancer cells. Proteins enriched in large EVs
      included enzymes involved in glucose, glutamine and amino acid metabolism, all
      metabolic processes relevant to cancer. Glutamine metabolism was altered in
      cancer cells exposed to large EVs, an effect that was not observed upon treatment
      with exosomes. Large EVs exhibited discrete buoyant densities in iodixanol
      (OptiPrep(TM)) gradients. Fluorescent microscopy of large EVs revealed an
      appearance consistent with LO morphology, indicating that these structures can be
      categorized as LO. Among the proteins enriched in LO, cytokeratin 18 (CK18) was
      one of the most abundant (within the top 5th percentile) and was used to develop
      an assay to detect LO in the circulation and tissues of mice and patients with
      prostate cancer. These observations indicate that LO represent a discrete EV type
      that may play a distinct role in tumor progression and that may be a source of
      cancer-specific markers.

PMID- 25857303
TI  - Aging Leads to a Dysregulation in Mechanically Driven Bone Formation and
      Resorption.
AB  - Physical activity is essential to maintain skeletal mass and structure, but its
      effect seems to diminish with age. To test the hypothesis that bone becomes less
      sensitive to mechanical strain with age, we used a combined in vivo/in silico
      approach. We investigated how maturation and aging influence the mechanical
      regulation of bone formation and resorption to 2 weeks of noninvasive in vivo
      controlled loading in mice. Using 3D in vivo morphometrical assessment of
      longitudinal microcomputed tomography images, we quantified sites in the mouse
      tibia where bone was deposited or resorbed in response to controlled in vivo
      loading. We compared the (re)modeling events (formation/resorption/quiescent) to
      the mechanical strains induced at these sites (predicted using finite element
      analysis). Mice of all age groups (young, adult, and elderly) responded to
      loading with increased formation and decreased resorption, preferentially at high
      strains. Low strains were associated with no anabolic response in adult and
      elderly mice, whereas young animals showed a strong response. Adult animals
      showed a clear separation between strain ranges where formation and resorption
      occurred but without an intermediate quiescent "lazy zone". This strain threshold
      disappeared in elderly mice, as mechanically induced (re)modeling became
      dysregulated, apparent in an inability to inhibit resorption or initiate
      formation. Contrary to what is generally believed until now, aging does not shift
      the mechanical threshold required to initiate formation or resorption, but rather
      blurs its specificity. These data suggest that pharmaceutical strategies
      augmenting physical exercise should consider this dysfunction in the mechanical
      regulation of bone (re)modeling to more effectively combat age-related bone loss.

PMID- 25857304
TI  - Social capital and all-cause mortality among Finnish men and women aged 30-79.
AB  - BACKGROUND: More knowledge is needed about how various dimensions of social
      capital associate with mortality either independently or mediated by other
      factors. In this cohort study, individual-level social capital was assessed as a
      possible predictor of all-cause mortality. METHODS: A 9-year mortality follow-up
      was conducted for participants of a nationally representative Health 2000 Survey
      carried out in 2000-01. The survey included a personal interview, self
      administered questionnaires and a health examination. Response rates to different
      items varied between 80 and 88%. Due to the item non-response, missing values
      were replaced by using multiple imputation. Participants (N = 6377) were 30-79
      years old at the baseline. During the follow-up period, 245 women and 340 men
      died. Cox regression models were used to assess the association between social
      capital and mortality. We analysed three dimensions of social capital: social
      support, social participation and trust. Their association with the risk of death
      was adjusted for several socio-demographic factors, health behaviours, health and
      biological risk factors. RESULTS: Unactive social participation was associated
      with higher mortality risk even when adjusting for the other factors. The
      association was stronger among men [hazard ratio (HR) = 1.56] than women (HR =
      1.42). The other two dimensions of social capital were associated with mortality
      when only age was adjusted for, but this association disappeared when social
      participation was included in the explanatory model. CONCLUSIONS: Active social
      participation protects against early death. This association is partly mediated
      through health behaviour and to a minor extent also through health.

PMID- 25857305
TI  - Indian government stalls roll-out of universal healthcare plan, report says.

PMID- 25857306
TI  - In support of assisted dying.

PMID- 25857307
TI  - Enhanced pulmonary vasodilator reserve and abnormal right ventricular: pulmonary
      artery coupling in heart failure with preserved ejection fraction.
AB  - BACKGROUND: Pulmonary hypertension and right ventricular (RV) dysfunction are
      common in patients with advanced heart failure with preserved ejection fraction
      (HFpEF), yet their underlying mechanisms remain poorly understood. We sought to
      examine RV-pulmonary artery (PA) functional reserve responses and RV-PA coupling
      at rest and during beta-adrenergic stimulation in subjects with earlier stage
      HFpEF. METHODS AND RESULTS: In a prospective trial, subjects with HFpEF (n=39)
      and controls (n=18) underwent comprehensive invasive and noninvasive hemodynamic
      assessment using high fidelity micromanometer catheters, echocardiography, and
      expired gas analysis at rest and during dobutamine infusion. HFpEF subjects
      displayed similar RV structure but significantly impaired RV systolic (lower RV
      dP/dtmax/IP and s') and diastolic function (higher RV tau) coupled with more
      severe pulmonary vascular disease, manifest by higher PA pressures, higher PA
      resistance, and lower PA compliance compared with controls. Dobutamine infusion
      caused greater pulmonary vasodilation in HFpEF compared with controls, with
      enhanced reductions in PA resistance, greater increase in PA compliance, and a
      more negative slope in the PA pressure-flow relationship when compared with
      controls (all P<0.001). RV-PA coupling analysis revealed that dobutamine improved
      RV ejection in HFpEF subjects through afterload reduction alone, rather than
      through enhanced contractility, indicating RV systolic reserve dysfunction.
      CONCLUSIONS: Pulmonary hypertension in early stage HFpEF is related to partially
      reversible pulmonary vasoconstriction coupled with RV systolic and diastolic
      dysfunction, even in the absence of RV structural remodeling. Pulmonary vascular
      tone is more favorably responsive to beta-adrenergic stimulation in HFpEF than
      controls, suggesting a potential role for beta-agonists in the treatment of
      patients with HFpEF and pulmonary hypertension. CLINICAL TRIAL REGISTRATION: URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT01418248.

PMID- 25857308
TI  - Low-Dose Systemic Alteplase (tPA) for the Treatment of Pulmonary Embolism.
AB  - OBJECTIVE: To review and evaluate the evidence regarding the use of low-dose
      regimens of alteplase (tPA) for the treatment of pulmonary embolism (PE). DATA
      SOURCES: A PubMed search (1966-January 2015) was conducted using the search terms
      pulmonary embolism, drug therapy, thrombolytic therapy, fibrinolytic agents, and
      tissue plasminogen activator. Articles were cross-referenced for additional
      citations. STUDY SELECTION AND DATA EXTRACTION: Clinical trials and case reports
      published in the English language assessing the use of low-dose systemic tPA for
      the treatment of PE were reviewed for inclusion. DATA SYNTHESIS: tPA is a
      thrombolytic agent indicated for the treatment of massive and submassive PE.
      Major bleeding complications of tPA are dose dependent and may occur in up to
      6.4% of patients. Clinical trials have demonstrated safety and efficacy of low
      dose tPA, particularly showing its benefit in patients with a low body weight
      (<65 kg) and right-ventricular dysfunction. Furthermore, case reports have safely
      used lower doses of tPA in patients at higher risk of bleeding, including
      elderly, pregnant, and surgical patients. CONCLUSIONS: The available data suggest
      that low-dose tPA may be a safe and effective treatment option for acute PE,
      particularly in patients at a high risk of bleeding. More studies are needed to
      determine the optimal dosing regimen of tPA for PE.

PMID- 25857309
TI  - Three-in-one parenteral nutrition in neonates and pediatric patients: risks and
      benefits.
AB  - Parenteral nutrition (PN) is a life-sustaining therapy designed to deliver
      essential nutrients to patients unable to meet nutrition needs via the enteral
      route. PN may be delivered via a 2-in-1 system (one solution containing amino
      acids, dextrose, electrolytes, vitamins, minerals, and fluids and one solution
      containing intravenous fat emulsions [IVFEs]) or via a 3-in-1 system (all
      nutrients mixed in one container). Although the use of 3-in-1 PN solutions is not
      necessarily therapeutically advantageous, certain benefits may exist such as the
      potential to reduce the risk of contamination due to decreased manipulations;
      ease of administration, particularly in the home care setting; possible cost
      savings; and reduced IVFE wastage. However, the incorporation of IVFE in 3-in-1
      solutions also presents unique risks for the neonatal and pediatric population
      such as decreased stability, increased lipid globule size, decreased sterility
      and the potential for increased microbial growth/infectious complications, the
      need to use a larger filter size, precipitation and compatibility risks, and an
      increased chance of catheter occlusion. This review outlines the unique issues
      and challenges to be considered when formulating neonatal and pediatric 3-in-1 PN
      admixtures. While 3-in-1 PN solutions may be advantageous for certain pediatric
      populations, specifically those dependent on home PN, the risks do not outweigh
      the benefits in neonatal patients, and use should be avoided in this population. 

PMID- 25857310
TI  - Age of G-1 PLUS v5 embryo culture medium is inversely associated with birthweight
      of the newborn.
AB  - STUDY QUESTION: Does age of G-1 PLUS v5 embryo culture medium affect IVF outcome?
      SUMMARY ANSWER: Birthweight of singletons born after IVF showed an inverse
      association with age of the embryo culture medium, while no association was found
      between age of culture medium and fertilization rate, embryonic development or
      ongoing pregnancy. WHAT IS KNOWN ALREADY: It has been reported that IVF culture
      media can deteriorate during storage, which suggests that the capacity of culture
      media to support optimal embryo development decreases over time. Some animal
      studies showed an effect of storage time on embryo development, in contrast to
      other studies, while the effect of aging culture medium on IVF outcome in humans
      is unknown. STUDY DESIGN, SIZE, DURATION: We used data on outcome of 1832
      IVF/ICSI cycles with fresh embryo transfer, performed in the period 2008-2012 to
      evaluate the association of fertilization rate, embryonic development, ongoing
      pregnancy and birthweight of singletons with age of the culture medium (Vitrolife
      AB G-1 PLUS v5). PARTICIPANTS/MATERIALS, SETTING, METHODS: Age of the culture
      medium was calculated by subtracting the production date from the date of ovum
      retrieval. Data analysis included linear regression and logistic regression on
      continuous and categorical outcomes, respectively. MAIN RESULTS AND THE ROLE OF
      CHANCE: Age of the culture medium was not associated with fertilization rate (P =
      0.543), early cleavage rate (P = 0.155), percentage of embryos containing four or
      more cells on Day 2 (P = 0.401), percentage of embryos containing eight or more
      cells on Day 3 (P = 0.175), percentage of embryos with multinucleated blastomeres
      (P = 0.527), or ongoing pregnancy (P = 0.729). However, birthweight of the
      newborn was inversely associated with age of the medium (beta = -3.6 g, SE: 1.5
      g, P = 0.021), after controlling for possible confounders (day of embryo
      transfer, number of transferred embryos, child's gender, gestational age at
      birth, parity, pregnancy complications, maternal smoking, height and weight, and
      paternal height and weight) and the association was not biased by year of
      treatment, time since first opening of the bottle or batch variations. This
      indicates a difference of 234 g in birthweight of newborns for media with an age
      difference of 65 days. LIMITATIONS, REASONS FOR CAUTION: The results from this
      study may be specific for the G-1 PLUS v5 culture medium and extrapolation of the
      results to other media should be done with caution because of the differences in
      composition and shelf life. WIDER IMPLICATIONS OF THE FINDINGS: Age of G-1 PLUS
      v5 medium used to culture human embryos affects birthweight of the respective
      newborn. This could imply that the preimplantation embryo adapts to its in vitro
      environment with lasting in vivo consequences. Therefore, it is important that
      companies are transparent about the exact composition of their embryo culture
      media, which will allow IVF clinics to further investigate the effects of the
      media or media components on the health of IVF children. STUDY FUNDING/COMPETING
      INTERESTS: No funding and no competing interests declared. TRIAL REGISTRATION
      NUMBER: Not applicable.

PMID- 25857311
TI  - Metabolic dysfunction in obese Hispanic women with polycystic ovary syndrome.
AB  - STUDY QUESTION: Are certain ethnic groups with polycystic ovary syndrome (PCOS)
      at increased risk of metabolic disorders? SUMMARY ANSWER: Obese Hispanic women
      with PCOS are at increased risk of metabolic disorders compared with age- and BMI
      matched obese non-Hispanic white women with PCOS in the USA. WHAT IS KNOWN
      ALREADY: Ethnic differences in body composition and metabolic risk are well
      established. PCOS is a common disorder in women of reproductive age and is
      associated with high rates of insulin resistance, glucose intolerance and
      dyslipidemia. STUDY DESIGN, SIZE, DURATION: A cross-sectional observational study
      was performed at an Academic Medical Center on 60 women of reproductive age with
      PCOS. PARTICIPANTS/MATERIALS, SETTING, METHODS: Blood was obtained after fasting
      from 17 Hispanic, 22 non-Hispanic black and 21 non-Hispanic white women with PCOS
      who were similar in age and BMI. Anthropometric parameters, insulin, lipid and
      lipoprotein levels (measured by nuclear magnetic resonance) were compared between
      the three groups. MAIN RESULTS AND THE ROLE OF CHANCE: Age and BMI did not differ
      between the groups. Hispanic women with PCOS had higher waist-to-hip ratio (WHR)
      (P = 0.02), homeostasis model assessment of insulin resistance (HOMA-IR) (P =
      0.03) and a more atherogenic lipid and lipoprotein profile consisting of lower
      high-density lipoprotein (HDL) (P = 0.02), higher low-density lipoprotein (LDL)
      particle number (P = 0.02), higher very low-density lipoprotein particle (VLDL)
      size (P = 0.03) and lower LDL (P = 0.03) and HDL particle size (P = 0.005)
      compared with non-Hispanic white women. The differences in HDL, HOMA-IR, VLDL and
      LDL size did not persist after adjustment for WHR while differences in LDL
      particle number (P = 0.04) and HDL size (P = 0.01) persisted. LIMITATIONS, REASON
      FOR CAUTION: The sample size for the three groups was small but the findings were
      still significant. The women were mostly obese so the ethnic differences in
      metabolic disorders may not apply to non-obese women with PCOS. WIDER
      IMPLICATIONS OF THE FINDINGS: Independent of BMI, obese, reproductive age,
      Hispanic women with PCOS in the USA had a greater degree of abdominal obesity,
      insulin resistance and dyslipidemia. Hispanic women with PCOS may benefit from
      more focused management of metabolic parameters. STUDY FUNDING/COMPETING
      INTERESTS: This project was supported by the following National Institutes of
      Health grants: K23 DK080988-01A1 to S.S. and UL1RR029879 to CTSA at University of
      Illinois. None of the authors report any conflict of interests.

PMID- 25857312
TI  - Regulation of smooth muscle dystrophin and synaptopodin 2 expression by actin
      polymerization and vascular injury.
AB  - OBJECTIVE: Actin dynamics in vascular smooth muscle is known to regulate
      contractile differentiation and may play a role in the pathogenesis of vascular
      disease. However, the list of genes regulated by actin polymerization in smooth
      muscle remains incomprehensive. Thus, the objective of this study was to identify
      actin-regulated genes in smooth muscle and to demonstrate the role of these genes
      in the regulation of vascular smooth muscle phenotype. APPROACH AND RESULTS:
      Mouse aortic smooth muscle cells were treated with an actin-stabilizing agent,
      jasplakinolide, and analyzed by microarrays. Several transcripts were upregulated
      including both known and previously unknown actin-regulated genes. Dystrophin and
      synaptopodin 2 were selected for further analysis in models of phenotypic
      modulation and vascular disease. These genes were highly expressed in
      differentiated versus synthetic smooth muscle and their expression was promoted
      by the transcription factors myocardin and myocardin-related transcription factor
      A. Furthermore, the expression of both synaptopodin 2 and dystrophin was
      significantly reduced in balloon-injured human arteries. Finally, using a
      dystrophin mutant mdx mouse and synaptopodin 2 knockdown, we demonstrate that
      these genes are involved in the regulation of smooth muscle differentiation and
      function. CONCLUSIONS: This study demonstrates novel genes that are promoted by
      actin polymerization, that regulate smooth muscle function, and that are
      deregulated in models of vascular disease. Thus, targeting actin polymerization
      or the genes controlled in this manner can lead to novel therapeutic options
      against vascular pathologies that involve phenotypic modulation of smooth muscle
      cells.

PMID- 25857313
TI  - Dimethylarginine dimethylaminohydrolase 2 regulates nitric oxide synthesis and
      hemodynamics and determines outcome in polymicrobial sepsis.
AB  - OBJECTIVE: Nitric oxide is a key to numerous physiological and pathophysiological
      processes. Nitric oxide production is regulated endogenously by 2
      methylarginines, asymmetric dimethylarginine (ADMA) and monomethyl-L-arginine.
      The enzyme that specifically metabolizes asymmetric dimethylarginine and
      monomethyl-L-arginine is dimethylarginine dimethylaminohydrolase (DDAH). The
      first isoform dimethylarginine dimethylaminohydrolase 1 has previously been shown
      to be an important regulator of methylarginines in both health and disease. This
      study explores for the first time the role of endogenous dimethylarginine
      dimethylaminohydrolase 2 in regulating cardiovascular physiology and also
      determines the functional impact of dimethylarginine dimethylaminohydrolase 2
      deletion on outcome and immune function in sepsis. APPROACH AND RESULTS: Mice,
      globally deficient in Ddah2, were compared with their wild-type littermates to
      determine the physiological role of Ddah2 using in vivo and ex vivo assessments
      of vascular function. We show that global knockout of Ddah2 results in elevated
      blood pressure during periods of activity (mean [SEM], 118.5 [1.3] versus 112.7
      [1.1] mm Hg; P=0.025) and changes in vascular responsiveness mediated by changes
      in methylarginine concentration, mean myocardial tissue asymmetric
      dimethylarginine (SEM) was 0.89 (0.06) versus 0.67 (0.05) MUmol/L (P=0.02) and
      systemic nitric oxide concentrations. In a model of severe polymicrobial sepsis,
      Ddah2 knockout affects outcome (120-hour survival was 12% in Ddah2 knockouts
      versus 53% in wild-type animals; P<0.001). Monocyte-specific deletion of Ddah2
      results in a similar pattern of increased severity to that seen in globally
      deficient animals. CONCLUSIONS: Ddah2 has a regulatory role both in normal
      physiology and in determining outcome of severe polymicrobial sepsis. Elucidation
      of this role identifies a mechanism for the observed relationship between Ddah2
      polymorphisms, cardiovascular disease, and outcome in sepsis.

PMID- 25857314
TI  - Cytotoxicity and hepatoprotective attributes of methanolic extract of Rumex
      vesicarius L.
AB  - BACKGROUND: To evaluate the hepatoprotective potential and invitro cytotoxicity
      studies of whole plant methanol extract of Rumex vesicarius L. Methanol extract
      at a dose of 100 mg/kg bw and 200 mg/kg bw were assessed for its hepatoprotective
      potential against CCl4-induced hepatotoxicity by monitoring activity levels of
      SGOT (Serum glutamic oxaloacetic transaminase), SGPT (Serum glutamic pyruvic
      transaminase), ALP (Alkaline phosphatase), TP (Total protein), TB (Total
      bilirubin) and SOD (Superoxide dismutase), CAT (Catalase), MDA (Malondialdehyde).
      The cytotoxicity of the same extract on HepG2 cell lines were also assessed using
      MTT assay method at the concentration of 62.5, 125, 250, 500 MUg/ml. RESULTS:
      Pretreatment of animals with whole plant methanol extracts of Rumex vesicarius L.
      significantly reduced the liver damage and the symptoms of liver injury by
      restoration of architecture of liver. The biochemical parameters in serum also
      improved in treated groups compared to the control and standard (silymarin)
      groups. Histopathological investigation further corroborated these biochemical
      observations. The cytotoxicity results indicated that the plant extract which
      were inhibitory to the proliferation of HepG2 cell line with IC50 value of 563.33
      +/- 0.8 MUg/ml were not cytotoxic and appears to be safe. CONCLUSIONS: Rumex
      vesicarius L. whole plant methanol extract exhibit hepatoprotective activity.
      However the cytotoxicity in HepG2 is inexplicable and warrants further study.

PMID- 25857315
TI  - New horizons in tumor microenvironment biology: challenges and opportunities.
AB  - The tumor microenvironment (TME) is being increasingly recognized as a key factor
      in multiple stages of disease progression, particularly local resistance, immune
      escaping, and distant metastasis, thereby substantially impacting the future
      development of frontline interventions in clinical oncology. An appropriate
      understanding of the TME promotes evaluation and selection of candidate agents to
      control malignancies at both the primary sites as well as the metastatic
      settings. This review presents a timely outline of research advances in TME
      biology and highlights the prospect of targeting the TME as a critical strategy
      to overcome acquired resistance, prevent metastasis, and improve therapeutic
      efficacy. As benign cells in TME niches actively modulate response of cancer
      cells to a broad range of standard chemotherapies and targeted agents, cancer
      oriented therapeutics should be combined with TME-targeting treatments to achieve
      optimal clinical outcomes. Overall, a body of updated information is delivered to
      summarize recently emerging and rapidly progressing aspects of TME studies, and
      to provide a significant guideline for prospective development of personalized
      medicine, with the long term aim of providing a cure for cancer patients. 

PMID- 25857316
TI  - An integrated approach to identifying and characterising resilient urban food
      systems to promote population health in a changing climate.
AB  - OBJECTIVE: To determine key points of intervention in urban food systems to
      improve the climate resilience, equity and healthfulness of the whole system.
      DESIGN: The paper brings together evidence from a 3-year, Australia-based mixed
      methods research project focused on climate change adaptation, cities, food
      systems and health. In an integrated analysis of the three research domains -
      encompassing the production, distribution and consumption sectors of the food
      chain - the paper examines the efficacy of various food subsystems (industrial,
      alternative commercial and civic) in achieving climate resilience and good
      nutrition. SETTING: Greater Western Sydney, Australia. SUBJECTS: Primary
      producers, retailers and consumers in Western Sydney. RESULTS: This overarching
      analysis of the tripartite study found that: (i) industrial food production
      systems can be more environmentally sustainable than alternative systems,
      indicating the importance of multiple food subsystems for food security; (ii) a
      variety of food distributors stocking healthy and sustainable items is required
      to ensure that these items are accessible, affordable and available to all; and
      (iii) it is not enough that healthy and sustainable foods are produced or sold,
      consumers must also want to consume them. In summary, a resilient urban food
      system requires that healthy and sustainable food items are produced, that
      consumers can attain them and that they actually wish to purchase them.
      CONCLUSIONS: This capstone paper found that the interconnected nature of the
      different sectors in the food system means that to improve environmental
      sustainability, equity and population health outcomes, action should focus on the
      system as a whole and not just on any one sector.

PMID- 25857317
TI  - Breeding objectives for sheep should be customised depending on variation in
      pasture growth across years.
AB  - Breeding programmes for livestock require economic weights for traits that
      reflect the most profitable animal in a given production system, which affect the
      response in each trait after selection. The profitability of sheep production
      systems is affected by changes in pasture growth as well as grain, meat and wool
      prices between seasons and across years. Annual pasture growth varies between
      regions within Australia's Mediterranean climate zone from low growth with long
      periods of drought to high growth with shorter periods of drought. Therefore, the
      objective of this study was to assess whether breeding objectives need to be
      adapted for regions, depending on how reliable the pasture growth is across
      years. We modelled farms with Merino sheep bred for wool and meat in 10 regions
      in Western Australia. Across these 10 regions, mean annual pasture growth
      decreased, and the CV of annual pasture growth increased as pasture growth for
      regions became less reliable. We calculated economic values for nine traits,
      optimising management across 11 years, including variation for pasture growth and
      wool, meat and grain prices between and within years from 2002 to 2012. These
      economic values were used to calculate responses to selection for each trait for
      the 10 regions. We identified two potential breeding objectives, one for regions
      with low or high reliability and the other for regions with medium reliability of
      pasture growth. Breeding objectives for high or low pasture growth reliability
      had more emphasis on live weight traits and number of lambs weaned. Breeding
      objectives for medium reliability of pasture growth had more emphasis on
      decreasing fibre diameter. Relative economic weights for fleece weight did not
      change across the regions. Regions with low or high pasture reliability had
      similar breeding objectives and response to selection, because the relationship
      between the economic values and CV of pasture growth were not linear for live
      weight traits and the number of lambs weaned. This non-linearity was caused by
      differences in distribution of pasture growth between regions, particularly
      during summer and autumn, when ewes were pregnant, with increases in energy
      requirements affecting the value of lambs weaned. In addition, increasing live
      weight increased the intake capacity of sheep, which meant that more poor quality
      pasture could be consumed during summer and autumn, which had more value in
      regions with low and high pasture reliability. We concluded that breeding values
      for sheep production systems should be customised depending on the reliability of
      pasture growth between years. 

PMID- 25857318
TI  - Ten-year trends in stroke admissions and outcomes in Canada.
AB  - BACKGROUND: We analyzed a 10-year stroke administrative dataset to examine trends
      in admissions, mortality, and discharge destination in Canada. METHODS: We
      conducted an analysis of hospital administrative data from April 1st 2003 to
      March 31st 2013 from the Canadian Institute of Health Information's Discharge
      Abstract Database. Ten-year trends for population-based age- and sex-standardized
      admission rates were calculated. We reviewed 10-year trends in absolute stroke
      admissions for differences between provinces and age groups. Stroke 30-day in
      hospital mortality rates were calculated and adjusted for sex, age, stroke type
      and comorbidities. We documented changes in discharge location for ischemic and
      hemorrhagic stroke patients discharged from acute care. RESULTS: The rate of
      hospital admissions has declined from 140.2 to 117.5 (per 100,000 people). The
      number of absolute stroke admissions within provinces increased in Alberta and
      British Columbia (21.7% and 16.2% respectively). The proportion of stroke
      patients aged 40-69 years old increased by 4.8% (p<0.0001) over the 10 years,
      whereas the proportion aged over 70 decreased by 4.9% (p<0.0001). Risk-adjusted
      30-day in-hospital mortality decreased from: 18.5% to 14.9% for all strokes;
      15.2% to 12.1% for ischemic strokes; 35.6% to 29.7% for intracerebral hemorrhage;
      and 25.1% to 18.0% for subarachnoid hemorrhage. The absolute increase in patients
      requiring inpatient and outpatient support increased by 4% (p<0.0001).
      CONCLUSION: The rate of admissions for stroke is decreasing but there is an
      increase in stroke admissions for younger patients. In-hospital mortality is
      decreasing; fewer patients are going directly home without services and more are
      requiring support services.

PMID- 25857320
TI  - Prostate-specific antigen-based screening: controversy and guidelines.
AB  - Although prostate-specific antigen (PSA) screening has improved the detection of
      prostate cancer, allowing for stage migration to less advanced disease, the
      precise mortality benefit of early detection is unclear. This is in part due to a
      discrepancy between the two large randomized controlled trials comparing PSA
      screening to usual care. The European Randomized Study of Screening for Prostate
      Cancer (ERSPC) found a survival benefit to screening, while the United States
      Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial did not.
      Furthermore, the benefit of immediate surgical intervention for screen-detected
      prostate cancer is unclear, as the results superficially differ between the two
      large randomized controlled trials comparing prostatectomy to observation. The
      Prostate Cancer Intervention Versus Observation Trial (PIVOT) found no survival
      benefit for prostatectomy in PSA screened U.S. men, while the Scandinavian
      Prostate Cancer Group Study Number Four (SPCG-4) found a survival benefit for
      prostatectomy in clinically diagnosed prostate cancer. As a result of the
      controversy surrounding PSA screening and subsequent prostate cancer treatment,
      guidelines vary widely by organization. 

PMID- 25857319
TI  - High genital prevalence of cutaneous human papillomavirus DNA on male genital
      skin: the HPV Infection in Men Study.
AB  - BACKGROUND: The genital skin of males hosts a diversity of HPV genotypes and
      uncharacterized HPV genotypes. Previously we demonstrated that a specific viral
      genotype was not identified in 14% of all genital specimens (i.e., HPV
      unclassified specimens) using the Roche Linear Array method. Our goal was to
      identify and assess the prevalence of individual HPV types among genital HPV
      unclassified specimens collected in the HIM Study population, at enrollment, and
      examine associations with socio-demographic and behavioral characteristics.
      METHODS: Genital skin specimens of men that were considered unclassified (HPV PCR
      positive, no genotype specified) at enrollment were typed by sequencing amplified
      PGMY09/11 products or cloning of PGMY/GP+ nested amplicons followed by
      sequencing. PGMY/GP+ negative specimens were further analyzed using FAP primers.
      HPV type classification was conducted through comparisons with sequences in the
      GenBank database. RESULTS: Readable nucleotide sequences were generated for the
      majority of previously unclassified specimens (66%), including both characterized
      (77%) and yet uncharacterized (23%) HPV types. Of the characterized HPV types,
      most (73%) were Beta [beta]-HPVs, primarily from beta-1 and beta-2 species,
      followed by Alpha [alpha]-HPVs (20%). Smokers (current and former) were
      significantly more likely to have an alpha-HPV infection, compared with any other
      genus; no other factors were associated with specific HPV genera or specific beta
      HPV species. CONCLUSIONS: Male genital skin harbor a large number of beta-HPV
      types. Knowledge concerning the prevalence of the diverse HPV types in the men
      genital is important to better understand the transmission of these viruses.

PMID- 25857322
TI  - Chrysin inhibits foam cell formation through promoting cholesterol efflux from
      RAW264.7 macrophages.
AB  - CONTEXT: Chrysin, a natural flavonoid, has been shown to possess multiple
      pharmacological activities including anti-atherosclerosis. OBJECTIVE: The effects
      of chrysin on foam cell formation and cholesterol flow in RAW264.7 macrophages
      were investigated in this work to explore the potential mechanism underlying its
      anti-atherogenic activity. MATERIALS AND METHODS: The inhibitive effect of
      chrysin on foam cell formation and cholesterol accumulation induced by oxidized
      low-density lipoprotein cholesterol (ox-LDL) was assessed by oil red O staining
      and intracellular total cholesterol and triglyceride quantification in RAW264.7
      macrophages. The action of chrysin on cholesterol efflux and influx was tested by
      fluorescent assays. Real-time quantitative PCR was used to quantify the relative
      expression of cholesterol flow-associated genes and luciferase assay was applied
      to test the transcription activity of peroxisome proliferator-activated receptor
      gamma (PPARgamma). RESULTS: Chrysin dose dependently inhibited the formation of
      foam cells and prevented the enhanced cholesterol accumulation by ox-LDL.
      Treatment with chrysin (10 MUM) significantly enhanced cholesterol efflux and
      substantially inhibited cholesterol influx. Simultaneously, chrysin significantly
      increased the mRNA levels of PPARgamma, liver X receptor alpha (LXRalpha), ATP
      binding cassette, sub-family A1 (ABCA1), and sub-family G1 (ABCG1), decreased
      scavenger receptor A1 (SR-A1) and SR-A2, and increased the transcriptional
      activity of PPARgamma. DISCUSSION AND CONCLUSION: Chrysin is a new inhibitor of
      foam cell formation that may stimulate cholesterol flow. Up-regulation of the
      classical PPARgamma-LXRalpha-ABCA1/ABCG1 pathway and down-regulation of SR-A1 and
      SR-A2 may participate in its suppressive effect on intracellular cholesterol
      accumulation.

PMID- 25857321
TI  - Genetic and morphological differentiation in Populus nigra L.: isolation by
      colonization or isolation by adaptation?
AB  - Identifying processes underlying the genetic and morphological differences among
      populations is a central question of evolutionary biology. Forest trees typically
      contain high levels of neutral genetic variation, and genetic differences are
      often correlated with geographic distance between populations [isolation by
      distance (IBD)] or are due to historic vicariance events [isolation by
      colonization (IBC)]. In contrast, morphological differences are largely due to
      local adaptation. Here, we examined genetic (microsatellite) and morphological
      (from a common garden experiment) variation in Populus nigra L., European black
      poplar, collected from 13 sites across western Europe and grown in a common
      garden in Belgium. Significant genetic differentiation was observed, with
      populations from France displaying greater admixture than the distinct Spanish
      and central European gene pools, consistent with previously described glacial
      refugia (IBC). Many quantitative traits displayed a bimodal distribution,
      approximately corresponding to small-leaf and large-leaf ecotypes. Examination of
      nine climatic variables revealed the sampling locations to have diverse climates,
      and although the correlation between morphological and climatic differences was
      significant, the pattern was not consistent with strict local adaptation. Partial
      Mantel tests based on multivariate summary statistics identified significant
      residual correlation in comparisons of small-leaf to large-leaf ecotypes, and
      within the small-leaf samples, but not within large-leaf ecotypes, indicating
      that variation within the small-leaf morphotype in particular may be adaptive.
      Some small-leaf populations experience climates very similar to those in large
      leaf sites. We conclude that adaptive differentiation and persistent IBC acted in
      combination to produce the genetic and morphological patterns observed in P.
      nigra. 

PMID- 25857323
TI  - Evaluation of the Food and Agriculture Sector Criticality Assessment Tool
      (FASCAT) and the Collected Data.
AB  - To protect and secure food resources for the United States, it is crucial to have
      a method to compare food systems' criticality. In 2007, the U.S. government
      funded development of the Food and Agriculture Sector Criticality Assessment Tool
      (FASCAT) to determine which food and agriculture systems were most critical to
      the nation. FASCAT was developed in a collaborative process involving government
      officials and food industry subject matter experts (SMEs). After development,
      data were collected using FASCAT to quantify threats, vulnerabilities,
      consequences, and the impacts on the United States from failure of evaluated food
      and agriculture systems. To examine FASCAT's utility, linear regression models
      were used to determine: (1) which groups of questions posed in FASCAT were better
      predictors of cumulative criticality scores; (2) whether the items included in
      FASCAT's criticality method or the smaller subset of FASCAT items included in
      DHS's risk analysis method predicted similar criticality scores. Akaike's
      information criterion was used to determine which regression models best
      described criticality, and a mixed linear model was used to shrink estimates of
      criticality for individual food and agriculture systems. The results indicated
      that: (1) some of the questions used in FASCAT strongly predicted food or
      agriculture system criticality; (2) the FASCAT criticality formula was a stronger
      predictor of criticality compared to the DHS risk formula; (3) the cumulative
      criticality formula predicted criticality more strongly than weighted criticality
      formula; and (4) the mixed linear regression model did not change the rank-order
      of food and agriculture system criticality to a large degree. 

PMID- 25857325
TI  - Comparative effectiveness of plasma prepared with amotosalen-UVA pathogen
      inactivation and conventional plasma for support of liver transplantation.
AB  - BACKGROUND: Liver transplant may require large-volume plasma transfusion with
      increased risk of transfusion-transmitted infection (TTI). Pathogen inactivation
      of plasma with amotosalen-UVA offers the potential to mitigate TTI risk. STUDY
      DESIGN AND METHODS: A retrospective cohort design was used to compare the
      therapeutic efficacy and key safety outcomes for liver transplants supported with
      quarantine plasma (Q-FFP [reference]) or amotosalen-UVA plasma (IBS plasma
      [test]). The outcomes evaluated were volume of plasma, the numbers of red blood
      cell (RBC) components, and the total dose of platelets (PLTs) transfused during
      and 7 days after transplant. The safety outcomes were acute hepatic artery
      thrombosis (HAT) and mortality. RESULTS: Transplantation and transfusion records
      for 212 Q-FFP transplants and 215 IBS plasma transplants were reviewed. Not all
      transplants required plasma; 161 received Q-FFP and 174 received IBS plasma.
      Among the transplants that required plasma, there were significant differences in
      median values between cohorts for delay to transplantation (p=0.002), model end
      stage liver disease score (p<0.001), pretransplant hematocrit (p=0.006), and
      graft cold perfusion time (p=0.033). The median volumes of plasma transfused were
      not different for test and reference (2.160 L vs. 1.969 L, p=0.292). Transplants
      in the test cohort required a mean of 3.7% more RBC components (p=0.767) and on
      average a 16.5% increase in total PLT dose (p=0.518). No significant differences
      were observed for the frequency of acute HAT or mortality. CONCLUSION: In this
      retrospective study, IBS plasma provided therapeutic support of liver transplant
      not different from Q-FFP.

PMID- 25857324
TI  - A Sativex((r)) -like combination of phytocannabinoids as a disease-modifying
      therapy in a viral model of multiple sclerosis.
AB  - BACKGROUND AND PURPOSE: Sativex((r)) is an oromucosal spray, containing
      equivalent amounts of Delta(9) -tetrahydrocannabinol (Delta(9) -THC) and
      cannabidiol (CBD)-botanical drug substance (BDS), which has been approved for the
      treatment of spasticity and pain associated to multiple sclerosis (MS). In this
      study, we investigated whether Sativex may also serve as a disease-modifying
      agent in the Theiler's murine encephalomyelitis virus-induced demyelinating
      disease model of MS. EXPERIMENTAL APPROACH: A Sativex-like combination of
      phytocannabinoids and each phytocannabinoid alone were administered to mice once
      they had established MS-like symptoms. Motor activity and the putative targets of
      these cannabinoids were assessed to evaluate therapeutic efficacy. The
      accumulation of chondroitin sulfate proteoglycans (CSPGs) and astrogliosis were
      assessed in the spinal cord and the effect of Sativex on CSPGs production was
      evaluated in astrocyte cultures. KEY RESULTS: Sativex improved motor activity -
      reduced CNS infiltrates, microglial activity, axonal damage - and restored myelin
      morphology. Similarly, we found weaker vascular cell adhesion molecule-1 staining
      and IL-1beta gene expression but an up-regulation of arginase-1. The astrogliosis
      and accumulation of CSPGs in the spinal cord in vehicle-infected animals were
      decreased by Sativex, as was the synthesis and release of CSPGs by astrocytes in
      culture. We found that CBD-BDS alone alleviated motor deterioration to a similar
      extent as Sativex, acting through PPARgamma receptors whereas Delta(9) -THC-BDS
      produced weaker effects, acting through CB2 and primarily CB1 receptors.
      CONCLUSIONS AND IMPLICATIONS: The data support the therapeutic potential of
      Sativex to slow MS progression and its relevance in CNS repair.

PMID- 25857326
TI  - Endothelial Function in Hypertension: Victim or Culprit?
AB  - Far from simply lining the inner surface of blood vessels, the cellular monolayer
      that comprises the endothelium is a highly active organ that regulates vascular
      tone. In health, the endothelium maintains the balance between opposing dilator
      and constrictor influences, while in disease, it is the common ground on which
      cardiovascular risk factors act to initiate the atherosclerotic process. As such,
      it is the site at which cardiovascular disease begins and consequently acts as a
      barometer of an individual's likely future cardiovascular health. The vascular
      endothelium is a very active organ responsible for the regulation of vascular
      tone through the effects of locally synthesized mediators, predominantly nitric
      oxide (NO), endothelial NO synthase (eNOS), and superoxide. NO is abundantly
      evident in normally functioning vasculature where it acts as a vasodilator,
      inhibits inflammation, and has an antiaggregant effect on platelets. Its
      depletion is both a sign and cause of endothelial dysfunction resulting from
      reduced activity of eNOS and amplified production of nicotinamide adenine
      dinucleotide oxidase, which, in turn, results in raised levels of reactive oxygen
      species. This cascade is the basis for reduced vascular compliance through an
      imbalanced regulation of tone with a predominance of vasoconstrictive elements.
      Further, structural changes in the microvasculature are a critical early step in
      the loss of normal function. This microvascular dysfunction is known to be highly
      predictive of future macrovascular events and is consequently a very attractive
      target for intervention in the hypertensive population in order to prevent
      cardiovascular events. 

PMID- 25857327
TI  - Accuracy of potassium supplementation of fluids administered intravenously.
AB  - BACKGROUND: Potassium (K+) supplementation of isotonic crystalloid fluids in
      daily fluid therapy is commonly performed, yet its accuracy in veterinary
      medicine is undetermined. OBJECTIVE: To investigate the accuracy of K+
      supplementation in isotonic crystalloid fluids. ANIMALS: None. METHODS:
      Observational study. 210 bags of fluid supplemented with KCl being administered
      to hospitalized dogs and cats intravenously (IV) were sampled over a 3-month
      period. Measured K+ concentration ([K+]) was compared to the intended [K+] of the
      bag. In a second experiment, 60 stock fluid bags were supplemented to achieve a
      concentration of 20 mmol/L K+, mixed well and [K+] was measured. In another 12
      bags of 0.9% NaCl, K+ was added without mixing the bag, and [K+ ] of the
      delivered fluid was measured at regular time points during constant rate
      infusion. RESULTS: The measured [K+] was significantly higher than intended [K+]
      (mean difference 9.0 mmol/L, range 6.5 to >280 mmol/L, P < .0001). In 28% of
      clinical samples measured [K+] was >=5 mmol/L different than intended [K+]. With
      adequate mixing, K+ supplementation of fluids can be accurate with the mean
      difference between measured and intended [K+] of 0.7 (95% CI -0.32 to 1.7)
      mmol/L. When not mixed, K(+) supplementation of 20 mmol/L can lead to very high
      [K+] of delivered fluid (up to 1410 mmol/L). CONCLUSIONS AND CLINICAL IMPORTANCE:
      Inadequate mixing following K+ supplementation of fluid bags can lead to
      potentially life threatening IV infused [K+]. Standard protocols for K+
      supplementation should be established to ensure adequate mixing.

PMID- 25857329
TI  - Front-line lenalidomide therapy in patients with newly diagnosed multiple
      myeloma.
AB  - The availability of novel drugs with different and innovative mechanisms of
      action such as proteasome inhibitors such as bortezomib and immunomdulatory
      agents as thalidomide and lenalidomide have changed the landscape of the
      treatment of patients with newly diagnosed multiple myeloma, allowing the
      development of several new therapeutic regimens both for transplant-eligible and 
      ineligible patients. Among these new agents, lenalidomide has become one of the
      most commonly used in these patients. In this article, we review the current
      state-of-the-art of different induction and maintenance lenalidomide-containing
      regimens administered in transplant-eligible and -ineligible patients with newly
      diagnosed multiple myeloma. We also discuss the safety profile and potential long
      term side effects of this drug and analyze its utility in certain subgroups of
      patients like those with high-risk disease or different degrees of renal
      impairment.

PMID- 25857331
TI  - The use of virtual world-based cardiac rehabilitation to encourage healthy
      lifestyle choices among cardiac patients: intervention development and pilot
      study protocol.
AB  - BACKGROUND: Despite proven benefits through the secondary prevention of
      cardiovascular disease (CVD) and reduction of mortality, cardiac rehabilitation
      (CR) remains underutilized in cardiac patients. Underserved populations most
      affected by CVD including rural residents, low socioeconomic status patients, and
      racial/ethnic minorities have the lowest participation rates due to access
      barriers. Internet-and mobile-based lifestyle interventions have emerged as
      potential modalities to complement and increase accessibility to CR. An
      outpatient CR program using virtual world technology may provide an effective
      alternative to conventional CR by overcoming patient access limitations such as
      geographics, work schedule constraints, and transportation. OBJECTIVE: The
      objective of this paper is to describe the research protocol of a two-phased,
      pilot study that will assess the feasibility (Phase 1) and comparative
      effectiveness (Phase 2) of a virtual world-based (Second Life) CR program as an
      extension of a conventional CR program in achieving healthy behavioral change
      among post-acute coronary syndrome (ACS) and post-percutaneous coronary
      intervention (PCI) patients. We hypothesize that virtual world CR users will
      improve behaviors (physical activity, diet, and smoking) to a greater degree than
      conventional CR participants. METHODS: In Phase 1, we will recruit at least 10
      patients enrolled in outpatient CR who were recently hospitalized for an ACS
      (unstable angina, ST-segment elevation myocardial infarction, non-ST-segment
      elevation myocardial infarction) or who recently underwent elective PCI at Mayo
      Clinic Hospital, Rochester Campus in Rochester, MN with at least one modifiable,
      lifestyle risk factor target (sedentary lifestyle, unhealthy diet, and current
      smoking). Recruited patients will participate in a 12-week, virtual world health
      education program which will provide feedback on the feasibility, usability, and
      design of the intervention. During Phase 2, we will conduct a 2-arm, parallel
      group, single-center, randomized controlled trial (RCT). Patients will be
      randomized at a 1:1 ratio to adjunct virtual world-based CR with conventional CR
      or conventional CR only. The primary outcome is a composite including at least
      one of the following (1) at least 150 minutes of physical activity per week, (2)
      daily consumption of five or more fruits and vegetables, and (3) smoking
      cessation. Patients will be assessed at 3, 6, and 12 months. RESULTS: The Phase 1
      feasibility study is currently open for recruitment which will be followed by the
      Phase 2 RCT. The anticipated completion date for the study is May 2016.
      CONCLUSIONS: While research on the use of virtual world technology in health
      programs is in its infancy, it offers unique advantages over current Web-based
      health interventions including social interactivity and active learning. It also
      increases accessibility to vulnerable populations who have higher burdens of CVD.
      This study will yield results on the effectiveness of a virtual world-based CR
      program as an innovative platform to influence healthy lifestyle behavior and
      self-efficacy.

PMID- 25857332
TI  - Ni(II)/BINOL-catalyzed alkenylation of unactivated C(sp(3))-H bonds.
AB  - The first nickel-catalyzed alkenylation of unactivated C(sp(3))-H bonds with
      vinyl iodides is described. The catalytic system comprises an inexpensive and air
      stable Ni(acac)2 as the catalyst and BINOL as the ligand, which is highly
      efficient for the alkenylation of beta-methyl C(sp(3))-H bonds of a broad range
      of aliphatic carboxamides. The resulting olefins can serve as versatile handles
      for further preparation. Additionally, we also demonstrated the synthesis of
      functionalized carboxamides bearing alpha-quaternary carbon centers from simple
      pivalamide via nickel-catalyzed sequential C(sp(3))-H bond functionalization. 

PMID- 25857330
TI  - Increased Turnover at Limiting O2 Concentrations by the Thr(387) -> Ala Variant
      of HIF-Prolyl Hydroxylase PHD2.
AB  - PHD2 is a 2-oxoglutarate, non-heme Fe(2+)-dependent oxygenase that senses O2
      levels in human cells by hydroxylating two prolyl residues in the oxygen
      dependent degradation domain (ODD) of HIF1alpha. Identifying the active site
      contacts that determine the rate of reaction at limiting O2 concentrations is
      crucial for understanding how this enzyme senses pO2 and may suggest methods for
      chemically altering hypoxia responses. A hydrogen bonding network extends from
      the Fe(II) cofactor through ordered waters to the Thr(387) residue in the second
      coordination sphere. Here we tested the impact of the side chain of Thr(387) on
      the reactivity of PHD2 toward O2 through a combination of point mutagenesis,
      steady state kinetic experiments and {FeNO}(7) EPR spectroscopy. The steady state
      kinetic parameters for Thr(387) -> Asn were very similar to those of wild-type
      (WT) PHD2, but kcat and kcat/KM(O2) for Thr(387) -> Ala were increased by roughly
      15-fold. X-Band electron paramagnetic resonance spectroscopy of the {FeNO}(7)
      centers of the (Fe+NO+2OG) enzyme forms showed the presence of a more rhombic
      line shape in Thr(387) -> Ala than in WT PHD2, indicating an altered conformation
      for bound gas in this variant. Here we show that the side chain of residue
      Thr(387) plays a significant role in determining the rate of turnover by PHD2 at
      low O2 concentrations.

PMID- 25857333
TI  - Laccaria bicolor aquaporin LbAQP1 is required for Hartig net development in
      trembling aspen (Populus tremuloides).
AB  - The development of ectomycorrhizal associations is crucial for growth of many
      forest trees. However, the signals that are exchanged between the fungus and the
      host plant during the colonization process are still poorly understood. In this
      study, we have identified the relationship between expression patterns of
      Laccaria bicolor aquaporin LbAQP1 and the development of ectomycorrhizal
      structures in trembling aspen (Populus tremuloides) seedlings. The peak
      expression of LbAQP1 was 700-fold higher in the hyphae within the root than in
      the free-living mycelium after 24 h of direct interaction with the roots.
      Moreover, in LbAQP1 knock-down strains, a non-mycorrhizal phenotype was developed
      without the Hartig net and the expression of the mycorrhizal effector protein
      MiSSP7 quickly declined after an initial peak on day 5 of interaction of the
      fungal hyphae with the roots. The increase in the expression of LbAQP1 required a
      direct contact of the fungus with the root and it modulated the expression of
      MiSSP7. We have also determined that LbAQP1 facilitated NO, H2 O2 and CO2
      transport when heterologously expressed in yeast. The report demonstrates that
      the L. bicolor aquaporin LbAQP1 acts as a molecular signalling channel, which is
      fundamental for the development of Hartig net in root tips of P. tremuloides. 

PMID- 25857334
TI  - The effect of balanced protein energy supplementation in undernourished pregnant
      women and child physical growth in low- and middle-income countries: a systematic
      review and meta-analysis.
AB  - The beneficial effect of balanced protein energy supplementation during pregnancy
      on subsequent child growth is unclear and may depend upon the mother entering
      pregnancy adequately nourished or undernourished. Systematic reviews to-date have
      included studies from high-, middle- and low-income countries. However, the
      effect of balanced protein energy supplementation should not be generalised. This
      review assesses the effect of balanced protein energy supplementation in
      undernourished pregnant women from low- and middle-income countries on child
      growth. A systematic review of articles published in English (1970-2015) was
      conducted via MEDLINE, Scopus, the Cochrane Register and hand searching. Only
      peer-reviewed experimental studies analysing the effects of balanced protein
      energy supplementation in undernourished pregnant women from low- and middle
      income countries with measures of physical growth as the primary outcome were
      included. Two reviewers independently assessed full-text articles against
      inclusion criteria. Validity of eligible studies was ascertained using the
      Quality Assessment Tool for Quantitative Studies (EPHPP QAT). In total, seven
      studies met the inclusion criteria. All studies reported on birthweight, five on
      birth length, three on birth head circumference, and one on longer-term growth.
      Standardised mean differences were calculated using a random-effects meta
      analysis. Balanced protein energy supplementation significantly improved
      birthweight (seven randomised controlled trials, n = 2367; d = 0.20, 95%
      confidence interval, 0.03-0.38, P = 0.02). No significant benefit was observed on
      birth length or birth head circumference. Impact of intervention could not be
      determined for longer-term physical growth due to limited evidence. Additional
      research is required in low- and middle-income countries to identify impacts on
      longer-term infant growth. 

PMID- 25857335
TI  - Serotonin Modulates Developmental Microglia via 5-HT2B Receptors: Potential
      Implication during Synaptic Refinement of Retinogeniculate Projections.
AB  - Maturation of functional neuronal circuits during central nervous system
      development relies on sophisticated mechanisms. First, axonal and dendritic
      growth should reach appropriate targets for correct synapse elaboration. Second,
      pruning and neuronal death are required to eliminate redundant or inappropriate
      neuronal connections. Serotonin, in addition to its role as a neurotransmitter,
      actively participates in postnatal establishment and refinement of brain wiring
      in mammals. Brain resident macrophages, that is, microglia, also play an
      important role in developmentally regulated neuronal death as well as in synaptic
      maturation and elimination. Here, we tested the hypothesis of cross-regulation
      between microglia and serotonin during postnatal brain development in a mouse
      model of synaptic refinement. We found expression of the serotonin 5-HT2B
      receptor on postnatal microglia, suggesting that serotonin could participate in
      temporal and spatial synchronization of microglial functions. Using two-photon
      microscopy, acute brain slices, and local delivery of serotonin, we observed that
      microglial processes moved rapidly toward the source of serotonin in Htr2B(+/+)
      mice, but not in Htr2B(-/-) mice lacking the 5-HT2B receptor. We then
      investigated whether some developmental steps known to be controlled by serotonin
      could potentially result from microglia sensitivity to serotonin. Using an in
      vivo model of synaptic refinement during early brain development, we investigated
      the maturation of the retinal projections to the thalamus and observed that
      Htr2B(-/-) mice present anatomical alterations of the ipsilateral projecting area
      of retinal axons into the thalamus. In addition, activation markers were
      upregulated in microglia from Htr2B(-/-) compared to control neonates, in the
      absence of apparent morphological modifications. These results support the
      hypothesis that serotonin interacts with microglial cells and these interactions
      participate in brain maturation. 

PMID- 25857336
TI  - Exploration of risk factors predicting outcomes for primary T1 high-grade bladder
      cancer and validation of the Spanish Urological Club for Oncological Treatment
      scoring model: Long-term follow-up experience at a single institute.
AB  - OBJECTIVE: To determine the prognostic factors of primary T1 high-grade bladder
      cancer and to validate the Spanish Urological Club for Oncological Treatment
      model in Japanese patients with T1 high-grade bladder cancer treated at a single
      institution. METHODS: Records of 106 patients with T1 high-grade bladder cancer
      treated from 1998 to 2013 were retrospectively reviewed. Variables included
      various clinicopathological parameters, including lymphovascular invasion and
      tumor growth pattern at the invasion front. Recurrence-free survival and
      progression-free survival were analyzed. Multivariate Cox proportional regression
      analysis was used to verify the prognostic significance of the variables. Scores
      for recurrence and progression were calculated using the Spanish Urological Club
      for Oncological Treatment model. RESULTS: Of 106 patients, 44 (42%) had
      recurrence and 16 (15%) developed progression after a median (interquartile
      range) follow-up period of 54 months (range 32-81 months). Non-papillary shape
      was the only independent predictor for recurrence, while broad-based tumor stalk
      and infiltrative tumor growth pattern at the invasion front were determined to be
      independent predictors for progression. Stratification of patients according to
      the number of progression risk factors yielded hazard ratios of 10.1 and 13.1 in
      patients having one and two risks, respectively, compared with those without any
      risks. The Spanish Urological Club for Oncological Treatment model successfully
      stratified our patients with a trend toward different probabilities of recurrence
      and progression. CONCLUSIONS: The results of the present study might be helpful
      for counseling certain patients towards intensive treatment, such as radical
      cystectomy and/or platinum-based systemic chemotherapy. In addition, the Spanish
      Urological Club for Oncological Treatment model might be applicable to Japanese
      patients with T1 high-grade bladder cancer.

PMID- 25857337
TI  - Pen size and parity effects on maternal behaviour of Small-Tail Han sheep.
AB  - The aim of this experiment was to study the effects of pen size and parity on
      maternal behaviour of twin-bearing Small-Tail Han ewes. A total of 24 ewes were
      allocated to a 2*2 design (six per pen), with parity (primiparous or multiparous)
      and pen size (large: 6.0*3.0 m; small: 6.0*1.5 m) as main effects at Linyi
      University, Shandong Province, China. Behaviour was observed from after
      parturition until weaning. All ewes were observed for 6 h every 5 days from 0700
      to1000 h and from 1400 to 1700 h. Continuous focal animal sampling was used to
      quantify the duration of maternal behaviours: sucking, grooming and following as
      well as the frequency of udder accepting, udder refusing and low-pitched
      bleating. Oestradiol and cortisol concentrations in the faeces (collected in the
      morning every 5 days) were detected using EIA kits. All lambs were weighed 24 h
      after parturition and again at weaning at 35 days of age. The small pen size
      significantly reduced following (P<0.005), grooming (P<0.001) and suckling
      durations (P<0.05), as well as the frequency of udder refusals (P<0.001).
      However, there was a significant interaction with ewe parity, with decreased
      grooming and suckling in the small pen largely seen in the multiparous ewes
      (P<0.001). Independent of pen size, multiparous ewes accepted more sucking
      attempts by their lambs (P<0.05) and made more low-pitched bleats than
      primiparous ewes (P<0.001). Multiparous ewes had higher faecal oestradiol
      concentrations than primiparous ewes (P<0.001), and ewes in small pens had higher
      faecal cortisol levels compared with ewes in larger pens (P<0.001). As lambs
      increased in age, the duration of maternal grooming, following and suckling as
      well as frequency of udder acceptance and low-pitched bleating all declined, and
      the frequency of udder refusing increased (P<0.001 for all). Ewe parity, but not
      pen size, affected lamb weight gain during the period of observation (P<0.001).
      This is the first study to show that pen size, interacting with parity, can
      affect the expression of maternal behaviour in sheep during lactation. The study
      is also the first to report on the maternal behaviour of Chinese native sheep
      breeds (Small-Tail Han sheep), with implications for the production of sheep in
      China. 

PMID- 25857338
TI  - Lipomatous tumours of the face in infants: diagnosis and treatment.
AB  - PURPOSE: The aim of this review is to present the different lipomatous tumours of
      the face typically found in infants. Lipomatous tumours induce a diagnostic
      challenge due to the low frequency, and the fact that the different lipomatous
      tumours mimic each other. METHOD: This study developed a flowchart for use in the
      evaluation of these tumours, including congenital infiltrating lipomatosis of the
      face, lipoblastomas, and liposarcomas. RESULTS AND CONCLUSIONS: The clinical
      presentation, histological features, imaging characteristics and treatment
      options are covered. It is suggested that a careful clinical examination is
      followed by magnetic resonance imaging. A histological analysis is often
      necessary to establish a definitive diagnosis, and a core needle biopsy is
      preferred in regards to sampling. Surgery is the treatment of choice, and should
      be performed by multidisciplinary teams in highly experienced centres. Individual
      surgical planning is mandatory.

PMID- 25857339
TI  - Effect of the MC1R gene on sexual dimorphism in melanin-based colorations.
AB  - Variants of the melanocortin-1 receptor (MC1R) gene result in abrupt, naturally
      selected colour morphs. These genetic variants may differentially affect sexual
      dimorphism if one morph is naturally selected in the two sexes but another morph
      is naturally or sexually selected only in one of the two sexes (e.g. to confer
      camouflage in reproductive females or confer mating advantage in males).
      Therefore, the balance between natural and sexual selections can differ between
      MC1R variants, as suggest studies showing interspecific correlations between
      sexual dimorphism and the rate of nonsynonymous vs. synonymous amino acid
      substitutions at the MC1R. Surprisingly, how MC1R is related to within-species
      sexual dimorphism, and thereby to sex-specific selection, has not yet been
      investigated. We tackled this issue in the barn owl (Tyto alba), a species
      showing pronounced variation in the degree of reddish pheomelanin-based
      coloration and in the number and size of black feather spots. We found that a
      valine (V)-to-isoleucine (I) substitution at position 126 explains up to 30% of
      the variation in the three melanin-based colour traits and in feather melanin
      content. Interestingly, MC1R genotypes also differed in the degree of sexual
      colour dimorphism, with individuals homozygous for the II MC1R variant being 2
      times redder and 2.5 times less sexually dimorphic than homozygous individuals
      for the VV MC1R variant. These findings support that MC1R interacts with the
      expression of sexual dimorphism and suggest that a gene with major phenotypic
      effects and weakly influenced by variation in body condition can participate in
      sex-specific selection processes. 

PMID- 25857340
TI  - pFe(3+) determination of multidentate ligands by a fluorescence assay.
AB  - The fluorescence intensity of the iron-CP691 complex in the presence of a
      competing multidentate ligand is associated with pFe(3+) of the competing ligand
      and the relative fluorescence has a linear correlation with the pFe(3+) values. A
      correlation was also found to exist between the relative fluorescence and the
      ratio of a competing ligand to the probe CP691. Based on this assay, the pFe(3+)
      value of a range of hexadentate ligands, dendrimers and polymers can be
      determined when they fall in the range 24.5-30.5. Only small quantities of
      chelators are required for this assay. 

PMID- 25857341
TI  - Advances in Alzheimer's disease drug development.
AB  - Alzheimer's disease (AD) is the foremost cause of dementia worldwide. Clinically,
      AD manifests as progressive memory impairment followed by a gradual decline in
      other cognitive abilities leading to complete functional dependency. Recent
      biomarker studies indicate that AD is characterized by a long asymptomatic phase,
      with the development of pathology occurring at least a decade prior to the onset
      of any symptoms. Current FDA-approved treatments target neurotransmitter
      abnormalities associated with the disease but do not affect what is believed to
      be the underlying etiology. In this review, we briefly discuss the most recent
      therapeutic strategies being employed in AD clinical trials, as well the
      scientific rationale with which they have been developed. 

PMID- 25857342
TI  - Facile synthesis and stereo-resolution of chiral 1,2,3-triazoles.
AB  - We describe herein the first facile synthesis of chiral triazoles through side
      chain functionalization. Readily available C-vinyl triazoles were used as
      starting materials, followed by sequential epoxidation, rearrangement and
      reduction to give the corresponding hydroxyl-triazoles. The CalB lipase catalyzed
      kinetic resolution gave enantiomerically pure (>99% ee) chiral triazoles in
      excellent yield. These new chiral TAs were also successfully applied as ligands
      in asymmetric addition of diethylzinc to aldehydes. 

PMID- 25857343
TI  - Intakes of apple juice, fruit drinks and soda are associated with prevalent
      asthma in US children aged 2-9 years.
AB  - OBJECTIVE: High soft drink consumption has been linked with asthma. Anecdotal
      evidence links high-fructose corn syrup with asthma. The receptor of advanced
      glycation end products (RAGE) has emerged as a mediator of asthma. The objectives
      of the present study were to: (i) assess the correlation between intake of
      beverages containing excess free fructose (EFF beverages) and asthma in children;
      and (ii) epidemiologically test the mechanistic hypothesis that intake of high
      EFF beverages, such as apple juice or beverages sweetened with high-fructose corn
      syrup, is associated with increased risk of asthma. This hypothesis is based on
      the possible effect of increases in the in situ intestinal formation of advanced
      glycation end products (enFruAGE) with EFF, which may be absorbed and play a role
      in RAGE-mediated asthma. DESIGN: We examined cross-sectional associations between
      beverage intake and self-reported current or history of asthma. Exposure
      variables were EFF beverages, including apple juice (AJ), non-diet soft drinks
      (ndSD) and fruit drinks (FD). Orange juice (OJ), not an EFF beverage, was
      included as a comparison. Rao-Scott chi(2) analysis was used for prevalence
      differences and logistic regression for associations, adjusted for age, sex,
      race/ethnicity, BMI and total energy intake. SETTING: Data are from the National
      Health and Nutrition Examination Survey 2003-2006, a nationally representative
      survey. SUBJECTS: US children (n 1961) aged 2-9 years with complete responses on
      the dietary frequency questionnaire. RESULTS: Intakes of EFF beverages were
      significantly associated with asthma in 2-9-year-olds. Adjusted odds of asthma in
      children consuming EFF beverages >=5 times/week was more than five times that in
      children consuming these beverages <=1 time/month (OR=5.29, P=0.012). Children
      consuming AJ >=5 times/week v. <=1 time/month, adjusted for the other beverages,
      were more than twice as likely to have asthma (OR=2.43, P=0.035). In contrast,
      there was a tendency for OJ to be protective. CONCLUSIONS: These results support
      the hypothesis that intake of high EFF beverages, including AJ and beverages
      sweetened with high-fructose corn syrup, is associated with asthma in children
      aged 2-9 years. Results support the mechanistic hypothesis that enFruAGE may be
      an overlooked contributor to asthma in children. Longitudinal studies are needed
      to provide evidence of causal association.

PMID- 25857344
TI  - A portable FRET analyzer for rapid detection of sugar content.
AB  - Fluorescence resonance energy transfer (FRET) is widely used as a core process in
      biometric sensors to detect small molecules such as sugars, calcium ions, or
      amino acids. However, FRET based biosensors with innate weak signal intensity
      require the use of expensive, high-sensitive equipment. In the present study,
      these shortcomings were overcome with the fabrication of a sensitive,
      inexpensive, and portable analyzer which provides quantitative detection of small
      molecules in a liquid sample. The usability of the developed analyzer was
      successfully tested by measuring sucrose and maltose contents in commercially
      available beverage samples, with better performance than the conventional
      monochromator-type spectrofluorometer. It is anticipated that miniaturization of
      the equipment and improving the FRET based biosensors will contribute to the
      practical use of this hand-held analyzer in conditions where high-end equipment
      is not available. 

PMID- 25857345
TI  - Reprogramming of myeloid angiogenic cells by Bartonella henselae leads to
      microenvironmental regulation of pathological angiogenesis.
AB  - The contribution of myeloid cells to tumour microenvironments is a decisive
      factor in cancer progression. Tumour-associated macrophages (TAMs) mediate tumour
      invasion and angiogenesis through matrix remodelling, immune modulation and
      release of pro-angiogenic cytokines. Nothing is known about how pathogenic
      bacteria affect myeloid cells in these processes. Here we show that Bartonella
      henselae, a bacterial pathogen causing vasculoproliferative diseases (bacillary
      angiomatosis), reprogrammes human myeloid angiogenic cells (MACs), a pro
      angiogenic subset of circulating progenitor cells, towards a TAM-like phenotype
      with increased pro-angiogenic capacity. B. henselae infection resulted in
      inhibition of cell death, activation of angiogenic cellular programmes and
      induction of M2 macrophage polarization. MACs infected with B. henselae
      incorporated into endothelial sprouts and increased angiogenic growth. Infected
      MACs developed a vascular mimicry phenotype in vitro, and expression of B.
      henselae adhesin A was essential in inducing these angiogenic effects. Secretome
      analysis revealed that increased pro-angiogenic activities were associated with
      the creation of a tumour-like microenvironment dominated by angiogenic
      inflammatory cytokines and matrix remodelling compounds. Our results demonstrate
      that manipulation of myeloid cells by pathogenic bacteria can contribute to
      microenvironmental regulation of pathological tissue growth and suggest parallels
      underlying both bacterial infections and cancer. 

PMID- 25857346
TI  - Antioxidant and anticholinesterase investigations of Rumex hastatus D. Don:
      potential effectiveness in oxidative stress and neurological disorders.
AB  - BACKGROUND: Rumex species are traditionally used for the treatment of
      neurological disorders including headache, migraine, depression, paralysis etc.
      Several species have been scientifically validated for antioxidant and
      anticholinestrase potentials. This study aims to investigate Rumex hastatus D.
      Don crude methanolic extract, subsequent fractions, saponins and flavonoids for
      acetylcholinestrase, butyrylcholinestrase inhibition and diverse antioxidant
      activities to validate its folkloric uses in neurological disorders. Rumex
      hastatus crude methanolic extract (Rh. Cr), subsequent fractions; n-hexane (Rh.
      Hex), chloroform (Rh. Chf), ethyl acetate (Rh. EtAc), aqueous fraction (Rh. Aq),
      crude saponins (Rh. Sp) and flavonoids (Rh. Fl) were investigated against
      acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) at various
      concentrations (125, 250, 500, 1000 MUg/mL) using Ellman's spectrophotometric
      analysis. Antioxidant potentials of Rh. Sp and Rh. Fl were evaluated using DPPH,
      H2O2 and ABTS free radical scavenging assays at 62.5, 125, 250, 500, 1000 MUg/mL.
      RESULTS: All the test samples showed concentration dependent cholinesterase
      inhibition and radicals scavenging activity. The AChE inhibition potential of Rh.
      Sp and Rh. Fl were most prominent i.e., 81.67 +/- 0.88 and 91.62 +/- 1.67 at
      highest concentration with IC50 135 and 20 MUg/mL respectively. All the
      subsequent fractions exhibited moderate to high AChE inhibition i.e., Rh. Cr, Rh.
      Hex, Rh. Chf, Rh. EtAc and Rh. Aq showed IC50 218, 1420, 75, 115 and 1210 MUg/mL
      respectively. Similarly, against BChE various plant extracts i.e., Rh. Sp, Rh.
      Fl, Rh. Cr, Rh. Hex, Rh. Chf, Rh. EtAc and Rh. Aq resulted IC50 165, 175, 265,
      890, 92, 115 and 220 MUg/mL respectively. In DPPH free radical scavenging assay,
      Rh. Sp and Rh. Fl showed comparable results with the positive control i.e., 63.34
      +/- 0.98 and 76.93 +/- 1.13% scavenging at 1 mg/mL concentration (IC50 312 and
      104 MUg/mL) respectively. The percent ABTS radical scavenging potential exhibited
      by Rh. Sp and Rh. Fl (1000 MUg/mL) were 82.58 +/- 0.52 and 88.25 +/- 0.67 with
      IC50 18 and 9 MUg/mL respectively. Similarly in H2O2 scavenging assay, the Rh. Sp
      and Rh. Fl exhibited IC50 175 and 275 MUg/mL respectively. CONCLUSION: The strong
      anticholinesterase and antioxidant activities of Rh. Sp, Rh. Fl and various
      fractions of R. hastatus support the purported ethnomedicinal uses and recommend
      R. hastatus as a possible remedy for the treatment of AD and neurodegenerative
      disorders.

PMID- 25857347
TI  - The development and maintenance of the mononuclear phagocyte system of the chick
      is controlled by signals from the macrophage colony-stimulating factor receptor.
AB  - BACKGROUND: Macrophages have many functions in development and homeostasis as
      well as innate immunity. Recent studies in mammals suggest that cells arising in
      the yolk sac give rise to self-renewing macrophage populations that persist in
      adult tissues. Macrophage proliferation and differentiation is controlled by
      macrophage colony-stimulating factor (CSF1) and interleukin 34 (IL34), both
      agonists of the CSF1 receptor (CSF1R). In the current manuscript we describe the
      origin, function and regulation of macrophages, and the role of CSF1R signaling
      during embryonic development, using the chick as a model. RESULTS: Based upon RNA
      sequencing comparison to bone marrow-derived macrophages grown in CSF1, we show
      that embryonic macrophages contribute around 2% of the total embryo RNA in day 7
      chick embryos, and have similar gene expression profiles to bone marrow-derived
      macrophages. To explore the origins of embryonic and adult macrophages, we
      injected Hamburger-Hamilton stage 16 to 17 chick embryos with either yolk sac
      derived blood cells, or bone marrow cells from EGFP+ donors. In both cases, the
      transferred cells gave rise to large numbers of EGFP+ tissue macrophages in the
      embryo. In the case of the yolk sac, these cells were not retained in hatched
      birds. Conversely, bone marrow EGFP+ cells gave rise to tissue macrophages in all
      organs of adult birds, and regenerated CSF1-responsive marrow macrophage
      progenitors. Surprisingly, they did not contribute to any other hematopoietic
      lineage. To explore the role of CSF1 further, we injected embryonic or hatchling
      CSF1R-reporter transgenic birds with a novel chicken CSF1-Fc conjugate. In both
      cases, the treatment produced a large increase in macrophage numbers in all
      tissues examined. There were no apparent adverse effects of chicken CSF1-Fc on
      embryonic or post-hatch development, but there was an unexpected increase in bone
      density in the treated hatchlings. CONCLUSIONS: The data indicate that the yolk
      sac is not the major source of macrophages in adult birds, and that there is a
      macrophage-restricted, self-renewing progenitor cell in bone marrow. CSF1R is
      demonstrated to be limiting for macrophage development during development in ovo
      and post-hatch. The chicken provides a novel and tractable model to study the
      development of the mononuclear phagocyte system and CSF1R signaling.

PMID- 25857348
TI  - Endocrine therapy considerations in postmenopausal patients with hormone receptor
      positive, human epidermal growth factor receptor type 2 negative advanced breast
      cancers.
AB  - The standard of care for patients with hormone receptor positive, human epidermal
      growth factor receptor type 2 negative advanced breast cancer is endocrine
      therapy. Endocrine agents, including aromatase inhibitors, tamoxifen, and
      fulvestrant, are often administered alone as first line treatment and demonstrate
      durable responses with limited side effects. Endocrine resistance represents a
      major clinical problem. In the future, poly-endocrine therapy and combination
      therapies with biological agents might become valuable options for the first line
      treatment of hormone receptor-positive advanced breast cancer. However, it will
      be critical to develop clinical tools that can reliably identify the subgroup of
      patients most likely to benefit from endocrine therapy alone, and those who might
      benefit from alternative approaches. Herein, we will review and discuss current
      issues in the endocrine treatment of postmenopausal patients with hormone
      receptor positive, human epidermal growth factor receptor type 2 negative
      advanced breast cancer.

PMID- 25857349
TI  - Radiation Dose from 3D Rotational vs. Conventional 2D Digital Subtraction
      Angiography in Intracranial Aneurysm Coiling.
AB  - PURPOSE: To compare patient effective dose resulting from two alternative imaging
      protocols for pre-coiling assessment of intracranial aneurysms: a series of 2D
      Digital Subtraction Angiography (DSA) projections, and a 3D rotational
      angiography (RA) acquisition. METHODS: In a retrospective analysis, we
      investigated 44 patients who underwent endovascular coiling in our institution.
      Images were acquired on a biplane Image Intensifier system not equipped with dose
      area product (DAP) meter. Conventional 2D DSA images were simulated with an
      anthropomorphic skull phantom. Entrance skin dose was measured with a 60 cc ion
      chamber, and the PCXMC Monte Carlo based software was used to calculate patient
      effective dose. For the RA protocol, a 16 cm computed tomography (CT) dosimetry
      phantom and a 100 mm pencil ion chamber were employed to measure the CT dose
      index. Patient effective dose was calculated with the ImPACT calculator. An
      unpaired two-tailed t-test was used to determine the significance of differences
      between patient doses in each group. RESULTS: Sixteen patients underwent the 2D
      DSA protocol with multiple projections; their mean number of cine runs was 5.1;
      the mean effective dose was 2.11 millisievert (mSv) (range 1.69-3.43 mSv). Twenty
      eight patients were assessed using the 3D RA protocol with the effective dose of
      1.29 mSv. The difference between the means of two dose distributions was
      statistically significant (p=0.00028). CONCLUSION: Our study demonstrated that
      the patient effective dose was significantly lower from the 3D RA protocol than
      that from the 2D DSA protocol used in the planning of coiling of intracranial
      aneurysm.

PMID- 25857350
TI  - MRL/MpJ-Fas(lpr) mice show abnormalities in ovarian function and morphology with
      the progression of autoimmune disease.
AB  - The immune system is known to affect reproductive function, and maternal-fetal
      immune tolerance is essential for a successful pregnancy. To investigate the
      relationship between autoimmune disease and female reproductive function, we
      performed a comparative analysis of the ovarian phenotypes for C57BL/6 mice,
      autoimmune disease-prone MRL/MpJ (MRL/+) mice and congenic MRL/MpJ-Fas(lpr)
      (MRL/lpr) mice harboring a mutation in the Fas gene that speeds disease onset.
      Both MRL-background strains showed earlier vaginal opening than C57BL/6 mice. The
      estrous cycle became irregular by 6 and 12 months of age in MRL/lpr mice and mice
      of the other two strains, respectively. Histological analysis at 3 months
      revealed that the number of primordial follicles was smaller in MRL-background
      mice than in C57BL/6 mice after 3 months. In addition, MRL/lpr and MRL/+ mice
      displayed lower numbers of ovarian follicles and corpora lutea at 3 and 6 months,
      and 6 and 12 months, respectively, than that in age-matched C57BL/6 mice. MRL/lpr
      and MRL/+ mice developed ovarian interstitial glands after 3 and 6 months,
      respectively. In particular, MRL/lpr mice showed numerous infiltrating
      lymphocytes within the ovarian interstitia, and partially stratified ovarian
      surface epithelia with more developed microvilli than that observed in C57BL/6
      mice at 6 months. No significant differences in serum hormone levels were
      observed between the strains. In conclusion, MRL/lpr mice display altered ovarian
      development, morphology and function consistent with the progression of severe
      autoimmune disease, as these findings are less severe in MRL/+ counterparts. 

PMID- 25857351
TI  - Increasing prevalence of multiple sclerosis in Vasterbotten County of Sweden.
AB  - OBJECTIVES: To update the incidence and prevalence of multiple sclerosis (MS) in
      Vasterbotten County, Sweden, and to compare this to previous investigations in
      the same area. BACKGROUND: Northern Sweden is a high-risk area for developing MS.
      Vasterbotten County has previously been surveyed in detail regarding the
      occurrence of MS. In several countries, increases in MS prevalence and incidence
      as well as a change in the sex ratio have been reported. MATERIALS AND METHODS:
      Multiple sources were used to identify MS cases in Vasterbotten that either had
      their onset of the disease from 1998 to 2010 and/or lived in Vasterbotten, the
      two dates chosen for prevalence calculation: the 31st of December 2005 and 2010.
      RESULTS: The mean yearly incidence of MS in Vasterbotten during the entire period
      1998-2010 was 6.0/100,000. The female to male ratio was 2.1. The prevalence of MS
      in Vasterbotten was 188/100,000 on 31st of December 2005 and 215/100,000 on 31st
      of December 2010. The MS prevalence increased over time from 1990 to 2010.
      CONCLUSIONS: The prevalence of MS in Vasterbotten County has increased between
      1990 and 2010, while no statistically significant increase in incidence was seen.

PMID- 25857353
TI  - Aldosterone and testosterone: two steroid hormones structurally related but with
      opposite electrophysiological properties during myocardial ischemia-reperfusion.
AB  - Steroid hormones appear to be a key factor in the gender differences in the rates
      and severity of cardiovascular diseases. Aldosterone and testosterone have
      typical steroid ring structure, but despite this, they demonstrate very different
      properties. During acute myocardial ischemia-reperfusion, the deleterious impact
      of aldosterone is now well established. Conversely, the electrophysiological
      impact of testosterone in this context remained unknown. We used female rabbit in
      vitro models and standard microelectrode technique including right ventricle
      mimicking the 'border zone' existing between normal and ischemic/reperfused areas
      and isolated right ventricle experiments to assess the acute electrophysiological
      impact of both aldosterone and testosterone. During ischemia-reperfusion, acute
      superfusion of 10 and 100 nmol/L testosterone decreased normoxic and reperfused
      action potential duration at 90% (APD90 ), systematically induced conduction
      blocks, and decreased APD90 dispersion between ischemic and nonischemic areas
      (from 98 +/- 4 to 57 +/- 7 ms and 66 +/- 3 ms, for, respectively, testosterone 10
      and 100 nmol/L, P < 0.05). Testosterone 10 and 100 nmol/L concomitantly decreased
      sustained premature ventricular contraction (PVC) occurrence (from 55 to 0%, P <
      0.05). Conversely, aldosterone 10 and 100 nmol/L increased normoxic and
      reperfused APD90 , APD90 dispersion, and reperfusion-induced PVCs. Furthermore,
      testosterone demonstrated cycle length-dependent effects on APD90 for high heart
      rate, whereas aldosterone did not exhibit any significant effect compared with
      controls. During acute myocardial ischemia-reperfusion, acute superfusion of
      physiological concentrations of testosterone seemed to be anti-arrhythmic by
      removing a pro-arrhythmic substrate (APD90 dispersion), inducing conduction
      blocks and decreasing triggered activities (PVC occurrence). Further experiments
      are warranted to confirm our results.

PMID- 25857352
TI  - RhoA and ROCK mediate histamine-induced vascular leakage and anaphylactic shock.
AB  - Histamine-induced vascular leakage is an integral component of many highly
      prevalent human diseases, including allergies, asthma and anaphylaxis. Yet, how
      histamine induces the disruption of the endothelial barrier is not well defined.
      By using genetically modified animal models, pharmacologic inhibitors and a
      synthetic biology approach, here we show that the small GTPase RhoA mediates
      histamine-induced vascular leakage. Histamine causes the rapid formation of focal
      adherens junctions, disrupting the endothelial barrier by acting on H1R Galphaq
      coupled receptors, which is blunted in endothelial Galphaq/11 KO mice.
      Interfering with RhoA and ROCK function abolishes endothelial permeability, while
      phospholipase Cbeta plays a limited role. Moreover, endothelial-specific RhoA
      gene deletion prevents vascular leakage and passive cutaneous anaphylaxis in
      vivo, and ROCK inhibitors protect from lethal systemic anaphylaxis. This study
      supports a key role for the RhoA signalling circuitry in vascular permeability,
      thereby identifying novel pharmacological targets for many human diseases
      characterized by aberrant vascular leakage. 

PMID- 25857354
TI  - The stability of short-term hearing outcome after stapedotomy: a prospective
      database study.
AB  - CONCLUSION: Current guidelines recommend reporting short-term results of > 12
      months after treatment of conductive hearing loss. This study suggests that short
      term hearing results after stapedotomy recorded at the 3-month follow-up are
      without loss of vital information compared with data from the currently
      recommended > 12-month follow-up. The use of 3-month data in reporting outcome
      could reduce the bias inherent to the loss to follow-up at 12 months. OBJECTIVE:
      To investigate the stability of short-term postoperative hearing after
      stapedotomy for otosclerosis. METHODS: This was a prospective database study; 371
      cases with otosclerosis were registered in the database between August 2004 and
      June 2013. We included the 166 primary cases and 37 revision cases that had
      attended both follow-ups. RESULTS: The mean changes in postoperative hearing
      thresholds between the 3-month and 12-month follow-up in both primary and
      revision cases were minimal and clinically insignificant. In all, 3-5% of primary
      cases and 14-16% of revision cases experienced a change of >= 10 dB for the worse
      of one or more parameters between follow-ups. Results were also stable when
      considering a range of traditional success criteria. Other complications
      following surgery were infrequent and typically resolved long term.

PMID- 25857355
TI  - Enhancing grain boundary ionic conductivity in mixed ionic-electronic conductors.
AB  - Mixed ionic-electronic conductors are widely used in devices for energy
      conversion and storage. Grain boundaries in these materials have nanoscale
      spatial dimensions, which can generate substantial resistance to ionic transport
      due to dopant segregation. Here, we report the concept of targeted phase
      formation in a Ce0.8Gd0.2O2-delta-CoFe2O4 composite that serves to enhance the
      grain boundary ionic conductivity. Using transmission electron microscopy and
      spectroscopy approaches, we probe the grain boundary charge distribution and
      chemical environments altered by the phase reaction between the two constituents.
      The formation of an emergent phase successfully avoids segregation of the Gd
      dopant and depletion of oxygen vacancies at the Ce0.8Gd0.2O2-delta-Ce0.8Gd0.2O2
      delta grain boundary. This results in superior grain boundary ionic conductivity
      as demonstrated by the enhanced oxygen permeation flux. This work illustrates the
      control of mesoscale level transport properties in mixed ionic-electronic
      conductor composites through processing induced modifications of the grain
      boundary defect distribution. 

PMID- 25857356
TI  - The combination of decoy receptor 3 and soluble triggering receptor expressed on
      myeloid cells-1 for the diagnosis of nosocomial bacterial meningitis.
AB  - BACKGROUND: Early diagnosis and appropriate antibiotic treatment can
      significantly reduce mortality of nosocomial bacterial meningitis. However, it is
      a challenge for clinicians to make an accurate and rapid diagnosis of bacterial
      meningitis. This study aimed at determining whether combined biomarkers can
      provide a useful tool for the diagnosis of bacterial meningitis. METHODS: A
      retrospective study was carried out. Cerebrospinal fluid (CSF) levels of decoy
      receptor 3 (DcR3) and soluble triggering receptor expressed on myeloid cells-1
      (sTREM-1) were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS:
      The patients with bacterial meningitis had significantly elevated levels of the
      above mentioned biomarkers. The two biomarkers were all risk factors with
      bacterial meningitis. The biomarkers were constructed into a "bioscore". The
      discriminative performance of the bioscore was better than that of each
      biomarker, with an area under the receiver operating characteristic (ROC) curve
      (AUC) of 0.842 (95% confidence intervals (CI) 0.770-0.914; p< 0.001).
      CONCLUSIONS: Combined measurement of CSF DcR3 and sTREM-1 concentrations improved
      the prediction of nosocomial bacterial meningitis. The combined strategy is of
      interest and the validation of that improvement needs further studies.

PMID- 25857357
TI  - The ellagic acid-derived gut microbiota metabolite, urolithin A, potentiates the
      anticancer effects of 5-fluorouracil chemotherapy on human colon cancer cells.
AB  - Chemotherapy increases the overall survival in colorectal cancer (CRC) patients.
      5-Fluorouracil (5-FU) remains as a drug of first choice in CRC therapy over the
      last four decades. However, only 10-15% of patients with advanced CRC respond
      positively to 5-FU monotherapy. Therefore, new strategies to enhance the 5-FU
      effectiveness, overcome the tumor cell resistance and decrease the unspecific
      toxicity are critically needed. Urolithin A (Uro-A) is the main metabolite
      produced by the human gut microbiota from the dietary polyphenol ellagic acid.
      Uro-A targets the colonic mucosa of CRC patients, and preclinical studies have
      shown the anti-inflammatory and cancer chemopreventive activities of this
      metabolite. We evaluated here whether Uro-A, at concentrations achievable in the
      human colorectum, could sensitize colon cancer cells to 5-FU and 5'DFUR (a pro
      drug intermediate of 5-FU). We found that both 5-FU and 5'DFUR arrested the cell
      cycle at the S phase by regulating cyclins A and B1 in the human colon cancer
      cells Caco-2, SW-480 and HT-29, and also triggered apoptosis through the
      activation of caspases 8 and 9. Co-treatments with Uro-A decreased IC50 values
      for both 5-FU and 5'DFUR and additionally arrested the cell cycle at the G2/M
      phase together with a slight increase in caspases 8 and 9 activation. Overall, we
      show that Uro-A potentiated the effects of both 5-FU and 5'DFUR on colon cancer
      cells. This suggests the need for lower 5-FU doses to achieve similar effects,
      which could reduce possible adverse effects. Further in vivo investigations are
      warranted to explore the possible role of Uro-A as a chemotherapy adjuvant. 

PMID- 25857359
TI  - VP2 capsid domain of the H-1 parvovirus determines susceptibility of human cancer
      cells to H-1 viral infection.
AB  - Although H-1 parvovirus is used as an antitumor agent, not much is known about
      the relationship between its specific tropism and oncolytic activity. We
      hypothesize that VP2, a major capsid protein of H-1 virus, determines H-1
      specific tropism. To assess this, we constructed chimeric H-1 viruses expressing
      Kilham rat virus (KRV) capsid proteins, in their complete or partial forms.
      Chimeric H-1 viruses (CH1, CH2 and CH3) containing the whole KRV VP2 domain could
      not induce cytolysis in HeLa, A549 and Panc-1 cells. However, the other chimeric
      H-1 viruses (CH4 and CH5) expressing a partial KRV VP2 domain induced cytolysis.
      Additionally, the significant cytopathic effect caused by CH4 and CH5 infection
      in HeLa cells resulted from preferential viral amplification via DNA replication,
      RNA transcription and protein synthesis. Modeling of VP2 capsid protein showed
      that two variable regions (VRs) (VR0 and VR2) of H-1 VP2 protein protrude
      outward, because of the insertion of extra amino-acid residues, as compared with
      those of KRV VP2 protein. This might explain the precedence of H-1 VP2 protein
      over KRV in determining oncolytic activity in human cancer cells. Taking these
      results together, we propose that the VP2 protein of oncolytic H-1 parvovirus
      determines its specific tropism in human cancer cells. 

PMID- 25857358
TI  - Anatomical location of LPA1 activation and LPA phospholipid precursors in rodent
      and human brain.
AB  - Lysophosphatidic acid (LPA) is a signaling molecule that binds to six known G
      protein-coupled receptors: LPA1 -LPA6 . LPA evokes several responses in the CNS,
      including cortical development and folding, growth of the axonal cone and its
      retraction process. Those cell processes involve survival, migration, adhesion
      proliferation, differentiation, and myelination. The anatomical localization of
      LPA1 is incompletely understood, particularly with regard to LPA binding.
      Therefore, we have used functional [(35) S]GTPgammaS autoradiography to verify
      the anatomical distribution of LPA1 binding sites in adult rodent and human
      brain. The greatest activity was observed in myelinated areas of the white matter
      such as corpus callosum, internal capsule and cerebellum. MaLPA1 -null mice (a
      variant of LPA1 -null) lack [(35) S]GTPgammaS basal binding in white matter
      areas, where the LPA1 receptor is expressed at high levels, suggesting a relevant
      role of the activity of this receptor in the most myelinated brain areas. In
      addition, phospholipid precursors of LPA were localized by MALDI-IMS in both
      rodent and human brain slices identifying numerous species of phosphatides and
      phosphatidylcholines. Both phosphatides and phosphatidylcholines species
      represent potential LPA precursors. The anatomical distribution of these
      precursors in rodent and human brain may indicate a metabolic relationship
      between LPA and LPA1 receptors. Lysophosphatidic acid (LPA) is a signaling
      molecule that binds to six known G protein-coupled receptors (GPCR), LPA1 to LPA6
      . LPA evokes several responses in the central nervous system (CNS), including
      cortical development and folding, growth of the axonal cone and its retraction
      process. We used functional [(35) S]GTPgammaS autoradiography to verify the
      anatomical distribution of LPA1 -binding sites in adult rodent and human brain.
      The distribution of LPA1 receptors in rat, mouse and human brains show the
      highest activity in white matter myelinated areas. The basal and LPA-evoked
      activities are abolished in MaLPA1 -null mice. The phospholipid precursors of LPA
      are localized by MALDI-IMS. The anatomical distribution of LPA precursors in
      rodent and human brain suggests a relationship with functional LPA1 receptors. 

PMID- 25857360
TI  - Zinc fingers and homeoboxes family in human diseases.
AB  - The zinc-fingers and homeoboxes (ZHX) family is a group of nuclear homodimeric
      transcriptional repressors that interact with a subunit of nuclear factor-Y (NF
      YA) and contain two C2H2-type zinc fingers and five homeobox DNA-binding domains.
      The members of ZHX family form homodimers or heterodimers with other members or a
      subunit of NF-YA to repress transcription. ZHX family members function in
      hematopoietic cell development and differentiation, and neural progenitor
      maintenance. Dysfunction of ZHX family members correlates with the development
      and progression of various diseases, including hepatocellular carcinoma (HCC),
      hematological diseases, neurological diseases and glomerular diseases.
      Furthermore, low expression of ZHX is associated with poor prognosis in
      malignancies. This review provides an update on the role of ZHX family in
      development and its function in cancer, with special emphasis on HCC and
      hematological malignant diseases. 

PMID- 25857361
TI  - Inhibition of pulmonary cancer progression by epidermal growth factor receptor
      targeted transfection with Bcl-2 and survivin siRNAs.
AB  - Clinical application of small interfering RNA (siRNA) in cancer therapy has been
      limited by the lack of an efficient systemic siRNA delivery system. In this
      report we describe an efficient siRNA delivery system directed to metastasized
      tumors, especially in the lungs. Anticancer siRNA was condensed in the presence
      of 9-arginine peptides (9Arg) and then complexed with cationic O,O'-dimyristyl-N
      lysyl glutamate liposomes conjugated to antibodies against the epidermal growth
      factor receptor (EGFR). The ternary complex of optimized anti-EGFR-9Arg
      lipoplexes exhibited efficient siRNA transfection of LS174T-Luc cancer cells
      grown in culture or orthotopically in mouse lungs. Anti-tumor Bcl-2/survivin
      siRNAs loaded in the anti-EGFR-9Arg-lipoplexes effectively suppressed
      transcription of their target genes, resulting in an efficient cancer cell death.
      Repeated intravenous administrations of the anti-EGFR-9Arg-lipoplexes effectively
      inhibited tumor growth in the mouse lungs and prolonged survival of the mice
      compared with nontargeted lipoplexes. These results suggest that the ternary
      complexes of anti-EGFR-9Arg-lipoplexes might have clinical applications in RNA
      interference cancer therapy. 

PMID- 25857362
TI  - Copper salts mediated morphological transformation of Cu2O from cubes to
      hierarchical flower-like or microspheres and their supercapacitors performances.
AB  - Monodisperse Cu2O of different microstructures, such as cubes, flower-like, and
      microspheres, have been extensively synthesized by a simple polyol reduction
      method using different copper salts, i.e. (Cu(acac)2, Cu(OH)2, and Cu(Ac)2.H2O).
      The effects of copper salts on the morphology of Cu2O were investigated in
      details through various characterization methods, including X-ray diffraction,
      transmission electron microscopy, scanning electron microscopy and UV-Vis
      absorption spectra. The effects of morphology on the electrochemical properties
      were further studied. Among the different structures, Cu2O with the microspheric
      morphology shows the highest specific capacitance and the best cycling stability
      compared with those of the other two structures, thus bear larger volume charge
      during the electrochemical reaction due to the microspheres of small
      nanoparticles. 

PMID- 25857363
TI  - Heat Stress Induces Extended Plateau of Hsp70 Accumulation--A Possible
      Cytoprotection Mechanism in Hepatic Cells.
AB  - The relevance of heat preconditioning resides in its ability to protect cells
      from different kinds of injury by induction of heat shock proteins, a process in
      which the intensity of heat stress (HS) and duration of subsequent recovery are
      vital. This study evaluates the effects of moderate HS (45 min/43 degrees C) and
      the time-dependent changes during recovery period of HSP70, Bcl-2 and p53 gene
      and protein expression in HepG2 cells. We also evaluated the effects of 0.4 mM
      aspirin (ASA) as a potential pharmacological co-inducer of HSP, both alone and in
      a combination with HS (ASA + HS). HS alone and ASA + HS caused a major up
      regulation of HSP70 mRNA in the first 2 h, while HSP70 protein increased
      gradually and was especially abundant from 2 h to 24 h. Regarding Bcl-2, all
      treatments rendered similar results: gene expression was down-regulated in the
      first 2 h, after which there was protein elevation (12-48 h after HS). mRNA
      expression of p53 in HS- and (ASA + HS)-cells was down-regulated in the first 12
      h. The immediate decrease of p53 protein after HS was followed by a biphasic
      increase. In conclusion, 0.4 mM ASA + HS does not act as a co-inducer of HSP70 in
      HepG2 cells, but promotes Bcl-2 protein expression during prolonged treatment.
      Our suggestion is that hepatic cells are most vulnerable in the first 2-6 h, but
      may have a high capacity for combating stress 12-24 h after HS. Finally, short
      term exposure HS might be a "physiological conditioner" for liver cells to
      accumulate HSP and Bcl-2 proteins and thus obtain cytoprotection against an
      additional stress.

PMID- 25857364
TI  - Immunomodulatory and immunorestorative activities of beta-D-glucan-rich extract
      and polysaccharide fraction of mushroom, Pleurutus tuberregium.
AB  - CONTEXT: Some edible mushrooms are reputed to possess useful medicinal properties
      which are related to their ability to modulate the protective responses of the
      immune system. OBJECTIVE: This study explored the immunomodulatory and
      immunorestorative properties of a hot aqueous extract (APTR) and of a beta-d
      glucan-enriched polysaccharide fraction (BGP) of a local oyster mushroom
      Pleurutus tuberregium (Fr.) Singer (Pleurotaceae). MATERIALS AND METHODS:
      Immunomodulatory activities were investigated by assessing specific and none
      specific immune responses in immunocompetent and immunosuppressed mice; as well
      as in vitro in culture of RAW264.7 macrophages stimulated with BGP. RESULTS: In a
      homologous prime-boost immunization schedule, oral supplementation with APTR
      (100, 200, or 400 mg/kg) and BGP (100 or 200 mg/kg) resulted in significantly
      higher titers of total IgG, IgG1, and IgG2a by as much as 2-4-folds compared with
      the levels in untreated control mice. The mean hemagglutination (HA) titer in
      immunized mice that were treated with dexamethasone (DEX; 5 mg/kg) was
      significantly (p < 0.05) lower than the titer in groups that did not receive
      dexamethasone; however, short-term alternate day administration of APTR (200
      mg/kg) to mice that had been immunosuppressed with 5 mg DEX/kg produced
      significant increases in secondary anti-SRBC antibody compared with the mean
      titer of mice immunized and treated with DEX alone. In in vitro studies,
      stimulation of RAW264.7 macrophages with BGP caused significant increases in iNO
      and TNF-alpha expression, and phagocytic functions of the cell. CONCLUSION: Taken
      together, the results of these studies showed that P. tuberregium imparts
      immunostimulatory and immunorestorative effects that could be explained, in part,
      by the actions of its beta-d-glucan constituent(s) on macrophages.

PMID- 25857365
TI  - Beef flavor: a review from chemistry to consumer.
AB  - This paper briefly reviews research that describes the sensation, generation and
      consumer acceptance of beef flavor. Humans sense the five basic tastes in their
      taste buds, and receptors in the nasal and sinus cavities sense aromas.
      Additionally, trigeminal senses such as metallic and astringent are sensed in the
      oral and nasal cavities and can have an effect on the flavor of beef. Flavors are
      generated from a complex interaction of tastes, tactile senses and aromas taken
      collectively throughout the tongue, nasal, sinus and oral cavities. Cooking beef
      generates compounds that contribute to these senses and result in beef flavor,
      and the factors that are involved in the cookery process determine the amount and
      type of these compounds and therefore the flavor generated. A low-heat, slow
      cooking method generates primarily lipid degradation products, while high-heat,
      fast cookery generates more Maillard reaction products. The science of consumer
      acceptance, cluster analyses and drawing relationships among all flavor
      determinants is a relatively new discipline in beef flavor. Consumers rate beef
      that has lipid degradation products generated from a low degree of doneness and
      Maillard flavor products from fast, hot cookery the highest in overall liking,
      and current research has shown that strong relationships exist between beef
      flavor and consumer acceptability, even more so than juiciness or tenderness.

PMID- 25857366
TI  - Effect of Silymarin Administration on Cisplatin Nephrotoxicity: Report from A
      Pilot, Randomized, Double-Blinded, Placebo-Controlled Clinical Trial.
AB  - Despite several introduced preventive modalities, cisplatin nephrotoxicity
      remains a clinical problem. Some in vitro and in vivo studies have addressed the
      protective effects of silymarin against cisplatin nephrotoxicity. This study
      evaluated the effects of silymarin administration on cisplatin nephrotoxicity as
      the first human study. During this pilot, randomized, double-blinded, placebo
      controlled clinical trial, the effect of oral silymarin 420 mg daily in three
      divided doses starting 24-48 h before the initiation of cisplatin infusion and
      continuing to the end of three 21-day cisplatin-containing chemotherapy courses
      on cisplatin-induced renal electrolytes wasting and kidney function were
      assessed. Cisplatin-associated acute kidney injury (AKI) occurred in 8% of the
      patients. Urine neutrophil gelatinase-associated lipocalin to urine creatinine
      ratio (NGAL/Cr) and urinary magnesium and potassium wasting increased
      significantly after cisplatin infusion in both groups. Significant positive
      correlation was found between cumulative dose of cisplatin and urine NGAL/Cr
      after three courses of cisplatin infusion. Incidence of AKI and the magnitude of
      urinary magnesium and potassium wasting did not differ between silymarin and
      placebo groups. No adverse reaction was reported by silymarin administration.
      Prophylactic administration of conventional form of silymarin tablets could not
      prevent cisplatin-induced urine electrolyte wasting or renal function impairment.

PMID- 25857367
TI  - Big data: Little difference.

PMID- 25857368
TI  - Pain research funding by the European Union Seventh Framework Programme.

PMID- 25857369
TI  - Aquaporin-4 knockdown ameliorates hypoxic-ischemic cerebral edema in newborn
      piglets.
AB  - Emerging evidence indicates that the water channel protein aquaporin 4 (AQP4)
      plays an essential role in water homeostasis and is implicated in the
      pathogenesis of brain edema. This study aimed to understand the physiological
      role of AQP4 in hypoxia-ischemia-mediated cytotoxic brain edema. We specifically
      knocked down AQP4 expression by intracerebral injection of a plasmid containing
      AQP4 siRNA into a neonatal piglet model. The success of the hypoxia-ischemia
      induced piglet model was confirmed by conventional magnetic resonance imaging and
      diffusion-weighted imaging. AQP4 knockdown led to reduced brain edema accompanied
      by a higher apparent diffusion coefficient value, compared to the control group
      injected with a plasmid containing scrambled siRNA. Real-time polymerase chain
      reaction and immunohistochemical analysis confirmed that AQP4 siRNA significantly
      reduced AQP4 mRNA and protein expression. Finally, neurological function analysis
      revealed that AQP4 knockdown significantly improved neurobehavioral manifestation
      of the piglets after exposure to hypoxia-ischemia. Taken together, these results
      indicate that AQP4 plays an important role in mediating brain edema in hypoxic
      ischemic encephalopathy. Therefore, AQP4 could be a therapeutic target to
      ameliorate early-stage brain edema.

PMID- 25857370
TI  - Activation of PPAR-delta induces microRNA-100 and decreases the uptake of very
      low-density lipoprotein in endothelial cells.
AB  - BACKGROUND AND PURPOSE: Increased level of very low-density lipoprotein (VLDL) is
      a key feature of the metabolic syndrome and is associated with cardiovascular
      diseases. PPAR-delta agonists play a protective role in lipid metabolism and
      vascular function. In this study, we aimed to investigate the role of PPAR-delta
      in the uptake of VLDL in endothelial cells and its underlying mechanism(s).
      EXPERIMENTAL APPROACH: Uptake of VLDL in HUVECs was assessed by Dil-fluorescent
      labelling of VLDL. Levels of VLDL receptor mRNA and microRNA (miR-100) were
      detected by quantitative PCR. The target genes of miR-100 were predicted using
      bioinformatics analysis. 3'-Untranslated region (3'-UTR) luciferase reporter and
      Argonaute 1 pull-down assays were used to validate the target of miR-100. KEY
      RESULTS: PPAR-delta agonist GW501516 decreased uptake of VLDL and expression of
      VLDL receptor at mRNA and protein levels. GW501516 inhibited the luciferase
      reporter activity of the 3'-UTR of VLDL receptor. VLDL receptor was a direct
      target of miR-100. miR-100 was significantly increased by GW501516 in HUVECs.
      Transfection of a miR-100 mimic decreased the mRNA and protein levels of VLDL
      receptor and uptake of VLDL. Furthermore, a miR-100 inhibitor abolished the
      inhibitory effect of PPAR-delta on VLDL receptor expression and VLDL uptake.
      CONCLUSIONS AND IMPLICATIONS: In endothelial cells, activation of PPAR-delta
      decreased VLDL receptor expression and VLDL uptake via the induction of miR-100.
      These results provided a novel mechanism for the vascular protective effect of
      PPAR-delta agonists.

PMID- 25857371
TI  - Transforming communication and safety culture in intrapartum care: a multi
      organization blueprint.
AB  - Effective, patient-centered communication facilitates interception and correction
      of potentially harmful conditions and errors. All team members, including women,
      their families, physicians, midwives, nurses, and support staff, have a role in
      identifying the potential for harm during labor and birth. However, the results
      of collaborative research studies conducted by organizations that represent
      professionals who care for women during labor and birth indicate that health care
      providers may frequently witness, but may not always report, problems with safety
      or clinical performance. Some of these health care providers felt resigned to the
      continuation of such problems and fearful of retribution if they tried to address
      them. Speaking up to address safety and quality concerns is a dynamic social
      process. Every team member must feel empowered to speak up about concerns without
      fear of put-downs, retribution, or receiving poor-quality care. Patient safety
      requires mutual accountability: individuals, teams, health care facilities, and
      professional associations have a shared responsibility for creating and
      sustaining environments of mutual respect and engaging in highly reliable
      perinatal care. Defects in human factors, communication, and leadership have been
      the leading contributors to sentinel events in perinatal care for more than a
      decade. Organizational commitment and executive leadership are essential to
      creating an environment that proactively supports safety and quality. The problem
      is well-known; the time for action is now. 

PMID- 25857373
TI  - Epidemiology, medical genetics, diagnosis and treatment of harlequin ichthyosis
      in Japan.
AB  - Ichthyoses are a group of disorders marked by whitish, brown or dark-brown scales
      on the skin of almost the whole body. Harlequin ichthyosis (HI) is the most
      severe form. Neonatal death from HI was once common. Due to intensive neonatal
      care and, probably, to the early introduction of oral retinoids, HI outcome has
      improved. For definitive diagnosis and the exclusion of other disorders, such as
      lamellar ichthyosis, which also shows a collodion baby phenotype, it is helpful
      to refer to electron microscopy of abnormal or absent lamellar granules and a
      heavy accumulation of lipid droplets in the keratinocytes. ATP-binding cassette
      transporter A12 (ABCA12) is known as the causative gene of HI. Severe ABCA12
      deficiency results in malformation of intercellular lipid layers in the cornified
      layers and leads to epidermal lipid barrier disruption. In HI patients, at least
      one mutation on each allele must be a truncation or deletion mutation to cause
      serious loss of ABCA12 function. Identification of the gene underlying HI has
      enabled DNA-based prenatal diagnosis for HI at the earlier stages of pregnancy
      with low risk. There are no curative treatments for HI. Abca12-deficient mice
      were created as a model of HI. Treatment of the model mice with retinoid or
      steroid has not been successful. 

PMID- 25857374
TI  - Pre-operative self-efficacy education vs. usual care for patients undergoing
      joint replacement surgery: a pilot randomised controlled trial.
AB  - BACKGROUND: Hip and knee replacement is a major surgical procedure performed
      worldwide. Despite 20 or so years of clinical research and care guidelines, the
      management of acute postoperative pain continues to be a concern. A growing
      number of self-efficacy strategies are being included in education programs for
      patients to enable then to have a central role in managing their illness and
      symptoms. AIMS AND OBJECTIVES: The purpose of this pilot study was to evaluate
      the feasibility of testing an education intervention to improve self-efficacy in
      patients undergoing hip or knee replacement. METHODS: A single-blinded, parallel,
      pilot randomised control trial design was used. Ninety-one patients undergoing
      hip or knee replacement surgery were randomly assigned to an intervention or
      control group. Intervention group participants were given a DVD demonstrating
      self-efficacy activities to undertake four times before admission. Feasibility
      criteria related to recruitment, protocol adherence and missing data were
      assessed. Participants were assessed for pain, anxiety, self-efficacy and
      healthcare utilisation. RESULTS: In relation to recruitment, 55% of screened
      patients were eligible and of these 81% enrolled (n = 91). Exclusion following
      randomisation was 10% with missing data ranging from 0 to 20.7%. Nineteen per
      cent of participants were lost to follow up in the control group and 20% lost to
      follow up in DVD group. Protocol adherence to components of the intervention
      varied. Both groups were generally satisfied with pain management during
      hospitalisation, and there were no differences in groups on clinical outcome
      measures. CONCLUSIONS: Preliminary evidence for the benefits of self-efficacy
      based education for patients undergoing hip or knee replacement was identified.
      Additional findings included a need to strengthen the intervention and reducing
      the number of data collection points to improve the protocol, missing data and
      numbers lost to follow up before a larger trial is undertaken.

PMID- 25857375
TI  - Controlling and culturing diversity: experimental zoology before World War II and
      Vienna's Biologische Versuchsanstalt.
AB  - Founded in Vienna in 1903, the Institute for Experimental Biology pioneered the
      application of experimental methods to living organisms maintained for sustained
      periods in captivity. Its Director, the zoologist Hans Przibram, oversaw until
      1938, the attempt to integrate ontogeny with studies of inheritance using precise
      and controlled measurements of the impact of environmental influences on the
      emergence of form and function. In the early years, these efforts paralleled and
      even fostered the emergence of experimental biology in America. But fate
      intervened. Though the Institute served an international community, most of its
      resident scientists and staff were of Jewish ancestry. Well before the Nazis
      entered Austria in 1938, these men and women were being fired and driven out;
      some, including Przibram, were eventually killed. We describe the unprecedented
      facilities built and the topics addressed by the several departments that made up
      this Institute, stressing those most relevant to the establishment and success of
      the Journal of Experimental Zoology, which was founded just a year later. The
      Institute's diaspora left an important legacy in North America, perhaps best
      embodied by the career of the developmental neuroscientist Paul Weiss.

PMID- 25857376
TI  - Virtual reality environments for healthcare professional education.

PMID- 25857377
TI  - The "Code of Ethics of the Italian National Institute of Health".

PMID- 25857378
TI  - NGF and therapeutic prospective: what have we learned from the NGF transgenic
      models?
AB  - It has been shown that topical nerve growth factor (NGF) administration induces
      healing action on human cutaneous, corneal and pressure ulcers, glaucoma,
      maculopathy and retinitis pigmentosa suggesting a therapeutic potential of NGF in
      human ophthalmology and cutaneous ulcers. A similar therapeutic suggestion has
      emerged for the NGF gene therapy of Alzheimer's disease and ischemic heart
      injury. Moreover, over the last few years, the role and biological properties of
      NGF have also been investigated with transgenic mice over-expressing and down
      expressing NGF. However, the results obtained with these transgenic mice seem
      suitable to confirm and/or support the evidence obtained with exogenous
      administration of NGF regarding the suggested clinical potentiality of NGF. The
      aim of the present brief review is to report and comment on these two different
      findings of NGF's healing properties. 

PMID- 25857379
TI  - A quality assessment of systematic reviews on telerehabilitation: what does the
      evidence tell us?
AB  - AIMS: To evaluate the quality of systematic reviews on telerehabilitation.
      METHODS: The AMSTAR--Assessment of Multiple Systematic Reviews--checklist was
      used to appraise the evidence related to the systematic reviews. RESULTS: Among
      the 477 records initially identified, 10 systematic reviews matched the inclusion
      criteria. Fifty percent were of high quality; anyway the majority of them did not
      report the following aspects: i) analysis of the grey literature; ii) a list of
      the excluded studies and their characteristics; iii) the identification of
      possible source of bias and the assessment of its likehood; iv) an appropriate
      method to combine the findings of the included studies addressing the
      heterogeneity as well. From the main findings of the high-scored systematic
      reviews telerehabilitation resulted at least as effective as usual care: 1) in
      the short term treatment of mental health related to people affected by spinal
      cord injury; 2) in rural communities for treating patients affected by chronic
      conditions; 3) in treating common pathologies (mainly asthma) affecting children
      and adolescents. As for stroke, evidence is currently insufficient to reach
      conclusions about its effectiveness. As for costs, there is insufficient evidence
      to confirm that telerehabilitation is a cost-saving or cost-effective solution.
      CONCLUSIONS: In the authors' knowledge this is the first attempt to evaluate the
      quality of systematic reviews on telerehabilitation. This work also identified
      the main findings related to the high-scored systematic reviews; the analysis
      confirms that there is a mounting evidence concerning the effectiveness of
      telerehabilitation, at least for some pathologies.

PMID- 25857380
TI  - Ethyl glucuronide in vitreous humor and blood postmortem specimens: analysis by
      liquid chromatography-electrospray tandem mass spectrometry and interpreting
      results of neo-formation of ethanol.
AB  - INTRODUCTION: The determination of ethyl glucuronide (EtG), a stable and
      sensitive marker that is specific to alcohol intake, finds many applications both
      in the forensic toxicology and clinical fields. AIM: The aim of the study is to
      examine the possibility of using a cadaveric biological matrix, vitreous humor
      (VH), to determine EtG as a marker of recent ethanol use. METHODS: The blood,
      taken from the femoral vein, and the VH were obtained from 63 autopsy cases.
      Analysis of the EtG was performed using an LC/MS/MS system. Analyses of the
      ethanol and putrefaction biomarkers, such as acetaldehyde and n-propanol, were
      performed using the HS-GC/FID technique in both the matrices. RESULTS: In 17
      cases, both ethanol and EtG were absent in both matrices.Nineteen cases presented
      ethanol in blood from 0.05 to 0.30 g/L, EtG-Blood concentration from 0.02 to 3.27
      mg/L, and EtG-VH concentration from 0.01 mg/L to 2.88 mg/L. Thirteen cases
      presented ethanol in blood > 0.05 g/L but EtG concentration in blood and VH lower
      than 0.01 mg/L, are part of these 8 samples presented acetic aldehyde and n-
      propanol in blood or VH, means identification of putrefaction indicators.
      Fourteen cases presented ethanol in blood > 0.46 and EtG concentration in blood
      and VH higher than 0.01 mg/L. CONCLUSIONS: The determination of EtG in biological
      material is important in those cases where the intake of ethanol appears
      doubtful, as it allows us to exclude the possibility of any post-mortem formation
      of ethanol.

PMID- 25857381
TI  - Incense, sparklers and cigarettes are significant contributors to indoor benzene
      and particle levels.
AB  - INTRODUCTION: The increased use of incense, magic candles and other flameless
      products often produces indoor pollutants that may represent a health risk for
      humans. Today, in fact, incense and air fresheners are used inside homes as well
      as in public places including stores, shopping malls and places of worship. As a
      source of indoor contamination, the impact of smoke, incense and sparklers on
      human health cannot be ignored. AIM: In the present work, we report the results
      of an emission study regarding particles (PM10 and particle number concentration,
      PNC) and benzene, produced by various incense sticks and sparklers. RESULTS AND
      DISCUSSION: The results obtained for benzene, PM10 and PNC, showed a strong
      negative influence on air quality when these products were used indoors. Various
      incense sticks gave completely different benzene results: from a small increase
      of the benzene concentration in the air, just slightly above the background
      levels of ambient air, to very high concentrations, of more than 200 ug/m of
      benzene in the test room after the incense sticks had been tested.

PMID- 25857382
TI  - Information retrieval for the Cochrane systematic reviews: the case of breast
      cancer surgery.
AB  - INTRODUCTION: Systematic reviews are fundamental sources of knowledge on the
      state-of-the-art interventions for various clinical problems. One of the
      essential components in carrying out a systematic review is that of developing a
      comprehensive literature search. MATERIALS AND METHODS: Three Cochrane systematic
      reviews published in 2012 were retrieved using the MeSH descriptor breast
      neoplasms/surgery, and analyzed with respect to the information sources used and
      the search strategies adopted. In March 2014, an update of one of the reviews
      retrieved was also considered in the study. RESULTS: The number of databases
      queried for each review ranged between three and seven. All the reviews reported
      the search strategies adopted, however some only partially. All the reviews
      explicitly claimed that the searches applied no language restriction although
      sources such as the free database Lilacs (in Spanish and Portuguese) was not
      consulted. CONCLUSION: To improve the quality it is necessary to apply standards
      in carrying out systematic reviews (as laid down in the MECIR project). To meet
      these standards concerning literature searching, professional information
      retrieval specialist staff should be involved. The peer review committee in
      charge of evaluating the publication of a systematic review should also include
      specialists in information retrieval for assessing the quality of the literature
      search.

PMID- 25857383
TI  - The role of associative and non-associative learning in the training of horses
      and implications for the welfare (a review).
AB  - Horses were domesticated 6000 years ago and since then different types of
      approaches have been developed to enhance the horse's wellbeing and the human
      horse relationship. Even though horse training is an increasingly important
      research area and many articles have been published on the subject, equitation is
      still the sport with the highest rate of human injuries, and a significant
      percentage of horses are sold or slaughtered due to behavioral problems. One
      explanation for this data is that the human-horse relationship is complex and the
      communication between humans and horses has not yet been accurately developed.
      Thus, this review addresses correct horse training based on scientific knowledge
      in animal learning and psychology. Specifically, it starts from the basic
      communication between humans and horses and then focuses on associative and non
      associative learning, with many practical outcomes in horse management from the
      ground and under saddle. Finally, it highlights the common mistakes in the use of
      negative reinforcement, as well as all the implications that improper training
      could have on horse welfare. Increased levels of competence in horse training
      could be useful for equine technicians, owners, breeders, veterinarians, and
      scientists, in order to safeguard horse welfare, and also to reduce the number of
      human injuries and economic loss for civil society and the public health system. 

PMID- 25857384
TI  - Pathologic diagnosis of malignant mesothelioma: chronological prospect and advent
      of recommendations and guidelines.
AB  - Malignant mesothelioma (MM) is rare and difficult to diagnose. Its identification
      depends upon pathological investigation (cyto-histological assessment and
      immunohistochemistry) supported by clinical and radiological evidence. In the
      last decade, the standardization of diagnostic methods has become a major focus
      of debate among pathologists and clinicians. This has led to the writing of
      guidelines and recommendation for the diagnosis to achieve the goal of a standard
      diagnosis. In this article, a chronological view relating to the pathological
      diagnosis of MM is presented together with a review of guidelines and
      recommendations. 

PMID- 25857385
TI  - Foodborne botulism associated with home-preserved turnip tops in Italy.
AB  - In Italy, foodborne botulism is a rare disease mainly due to home-preserved food.
      In the case reported here, clinical diagnosis was performed on the basis of
      clinical signs and referred consumption of home-preserved turnip tops in oil.
      Definitive diagnosis was performed by detection of botulinum toxin in sera and
      neuro-toxigenic organisms in stools and leftover food. This case report
      highlights the need of a high medical awareness, prompt clinical diagnosis, and
      synergic collaboration among the health authorities for a correct management of
      botulism as well as disease containment. 

PMID- 25857386
TI  - A study on prophagic and chromosomal sodC genes involvement in Escherichia coli
      O157:H7 biofilm formation and biofilm resistance to H2O2.
AB  - INTRODUCTION: Escherichia coli O157:H7 possesses one chromosomal and two
      prophagic sodC genes encoding for Cu,Zn superoxide dismutases. We evaluated the
      contribution of sodC genes in biofilm formation and its resistance to hydrogen
      peroxide. METHODS: The biofilm of sodC deletion mutants has been studied, in
      presence or absence of hydrogen peroxide, by crystal violet in 96-well plates and
      Scanning Electron Microscopy on glass coverslips. RESULTS: Deletion of prophagic
      sodC genes had no effect on biofilm construction, in contrast to the chromosomal
      gene deletion. Hydrogen peroxide treatment showed higher cell mortality and
      morphological alterations in sodC deletion mutants respect to wild type. These
      effects were related to the biofilm development stage. CONCLUSION: The role of
      the three SodCs is not redundant in biofilm formation and the resistance to
      oxidative damage. The stage of biofilm development is a crucial factor for an
      effective sanitization.

PMID- 25857387
TI  - Preliminary investigation on tick fauna in the neighborhood of Tarquinia, Lazio,
      Italy.
AB  - INTRODUCTION: This study represents a preliminary inquiry on tick fauna
      composition carried out in Maremma, Central Italy, where very few data are
      available. MATERIALS AND METHODS: The study area was selected in the limestone
      hills surrounding Tarquinia town, on the base of suitable elements directly
      affecting the tick occurrence and the possible circulation of tick-borne
      pathogens, such as wild cattle rearing, kind of vegetation and human activities.
      Since a proper understanding of tick ecology is critical in predicting the risk
      of tick-borne pathogen transmission in a given area, a series of surveys was
      planned in such area in 2011. RESULTS: One hundred fifty-four ticks belonging to
      4 genera and 6 species, namely Ixodes ricinus (n. = 109; 70%), Rhipicephalus
      bursa (n. = 18; 12%), Rhipicephalus turanicus (n. = 14; 9%), Rhipicephalus
      sanguineus (n. = 6; 4%), Hyalomma marginatum (n. = 4; 3%) and Dermacentor
      marginatus (n. = 3; 2%) were identified and reported for the area. DISCUSSION:
      The results of this acarological research represent a significant contribution to
      the knowledge of the tick fauna of rural areas in Northern Lazio Region, as first
      step toward a future molecular investigation on pathogen circulation.

PMID- 25857388
TI  - Barriers in the management of cancer-related pain and strategies to overcome
      them: findings of a qualitative research involving physicians and nurses in
      Italy.
AB  - INTRODUCTION AND AIMS: There are many barriers and obstacles that even today lead
      to an inadequate treatment of cancer-related pain. The aim is to describe the
      experiences of a group of Italian physicians and nurses as far as the nature of
      these barriers is concerned and the possible tools to be used to overcome them.
      MATERIAL AND METHOD: We run 5 focus groups with 42 healthcare professionals (11
      physicians, 31 nurses) working in 5 hospitals in Italy. The findings of the focus
      groups were analysed according to the "Content Analysis" method. RESULTS: Five
      main items emerged: the importance of communication, the need for education
      regarding pain therapy, the ethnic/cultural/religious differences, the mutual
      trust and support within the working group, the daily challenges. CONCLUSION: In
      harmony with the most recent literature, physicians and nurses voice above all
      their need for an education more directly aimed at overcoming the prevailing
      barriers rooted in ignorance, prejudice and fears.

PMID- 25857389
TI  - The perception of the fetus in mothers with liver transplantation. Brief
      communication.
AB  - BACKGROUND: In this brief note we present the preliminary findings of a study of
      16 women who underwent liver transplants before becoming pregnant and giving
      birth. The aim of the study was to show the similarities and differences between
      ways women experience the transplanted organ (liver) and the fetus. METHODS: To
      explore bodily experiences, a semi-structured ad hoc interview was done on a
      sample of 16 transplanted women who had completed a pregnancy. The interview was
      designed to explore the possible similarities between their perception of the
      transplanted organ (liver) and of the fetus. RESULTS: The main findings that
      emerge from our study are the following: a) in the post-transplant, pre-pregnancy
      phase, these women develop a polarized attention on the transplanted organ; b)
      during pregnancy this attention shifts towards the fetus; c) after childbirth the
      hyper-attention on the transplanted organ disappears and the subject resumes a
      normal relationship with her body. CONCLUSIONS: Therefore, pregnancy and
      childbirth are experiences that can normalize relations between a person who has
      undergone a transplant and their transplanted organ.

PMID- 25857392
TI  - New Insights Into Androgen and Estrogen Receptor Regulation of the Male Skeleton.

PMID- 25857393
TI  - Improving red blood cell orders, utilization, and management with point-of-care
      clinical decision support.
AB  - BACKGROUND: The computerized order for red blood cell (RBC) transfusion within
      our electronic health record was redesigned with integrated clinical decision
      support (CDS) to reinforce our restrictive transfusion policy. These changes
      encouraged 1-unit (1U) RBC orders, clarified hemoglobin (Hb) transfusion
      triggers, and discouraged unnecessary orders. This study assessed whether these
      changes resulted in durable effects on provider practices. STUDY DESIGN AND
      METHODS: The study compared three 1-year subperiods from August 2011 to August
      2014, with each year corresponding to a historical control period,
      preintervention and postintervention years. This study analyzed ratios of 1U
      versus 2-unit (2U) orders and the absolute rate of RBC orders, units charged, Hb
      transfusion triggers, repeat transfusion orders, and selected clinical
      indications both institution-wide and across several subpopulations. RESULTS: Our
      institution-wide ratio of 1U versus 2U orders increased from 0.50 to 1.20 (p <
      0.0001) in the pre- to postintervention subperiods, respectively. The number of
      units charged per day decreased from 15.68 to 13.53 (p < 0.001), while rates of
      initial and repeat orders remained stable. Proportion of clinical indications
      used and mean Hb triggers demonstrated generally positive results. The changes
      observed between the pre- and postintervention years were far greater than
      changes between historical control versus preintervention years, reinforcing
      attribution of results to computerized physician order entry changes. CONCLUSION:
      Use of computerized orders and CDS encouraged a restrictive transfusion policy,
      which was highly successful in changing provider practices. We also succeeded in
      decreasing mean Hb triggers and overall utilization of RBCs. These findings
      persisted across many subpopulations.

PMID- 25857395
TI  - The Incidence of Posttraumatic Stress Disorder After Floods: A Meta-Analysis.
AB  - This study analyzes the incidence of posttraumatic stress disorder (PTSD) among
      flood victims, between different flood intensities, and between different time
      points after a flood. A search of several electronic literature databases was
      conducted to collect data on the incidence of PTSD after a flood. Loney criteria
      for research quality were used to evaluate the quality of selected search
      results. The combined incidence of PTSD was estimated using the Freeman-Tukey
      double arcsine transformation method. Subgroup analyses were conducted on
      different trauma intensities and different time points after a flood. Sensitivity
      analysis was performed to evaluate the impact of research quality. Fourteen
      articles were included in this meta-analysis, including a total of 40 600 flood
      victims; 3862 victims were diagnosed with PTSD. The combined incidence of PTSD
      was 15.74%. The subgroup analyses showed that the incidence of PTSD in victims
      who experienced severe and moderate flood intensity was higher than that in
      victims who experienced mild flood intensity. The incidence of PTSD was lower at
      6 or more months after a flood (11.45%) than within 6 months (16.01%) of a flood.
      In conclusion, the incidence of PTSD among floods of different trauma intensities
      was statistically significant.

PMID- 25857394
TI  - Randomized placebo-controlled clinical trial of a chewable formulation of
      amlodipine for the treatment of hypertension in client-owned cats.
AB  - BACKGROUND: There is an unmet clinical need for a cat-specific formulation of
      amlodipine to treat hypertensive cats. OBJECTIVES: To assess the efficacy of
      chewable amlodipine tablets in reducing systolic blood pressure (SBP) in cats
      diagnosed with systemic arterial hypertension. ANIMALS: Seventy-seven client
      owned cats with systemic hypertension were included (median age 14 years).
      METHODS: The study was randomized, double-blinded, and placebo-controlled. Forty
      two cats received 0.125-0.50 mg/kg amlodipine once daily for 28 days; 35 cats
      received placebo. After 28 days all cats continued with amlodipine for 2-3 months
      in an open-label phase. Blood pressure was measured using high definition
      oscillometry. A responder was defined as a cat showing a decrease of SBP to <150
      mmHg at 28 days or a decrease from baseline >=15%. RESULTS: Sixty-one cats
      completed the study. The responder rate was 63% in amlodipine group and 18% in
      placebo group. Cats receiving amlodipine were 7.9 (95% CI 2.6-24.1) times more
      likely to be classified as responders when compared to those receiving placebo (P
      < .001). From a mean (+/-SD) baseline value of 181 (+/-12) mmHg, SBP decreased to
      154 (+/-17) mmHg with amlodipine and to 170 (+/-21) mmHg with placebo (P < .001).
      The voluntary acceptance rate of amlodipine formulation was 73%. CONCLUSIONS AND
      CLINICAL IMPORTANCE: The chewable amlodipine tablet effectively reduced SBP
      compared with placebo in hypertensive cats, and was well-tolerated. It can be
      used concomitantly with angiotensin-converting enzyme inhibitors and in cats with
      chronic kidney disease.

PMID- 25857396
TI  - Organic matter and macromineral digestibility in domestic rabbits (Oryctolagus
      cuniculus) as compared to other hindgut fermenters.
AB  - It is generally assumed that animal species differ in physiological
      characteristics of their digestive tract. Because investigating digestive
      processes is often labour-intensive, requiring lengthy adaptation and collection
      periods, comparisons are often made on the basis of data collated from different
      studies. We added a new data set on dietary crude fibre (CF) and macromineral
      (Na, K, Ca, P, Mg) composition and apparent digestibility (aD) of organic matter
      (OM) and macrominerals in rabbits (Oryctolagus cuniculus; a total of 180
      measurements with 12 individuals and 10 different diets) to a literature data
      collection for rodents and domestic horses (Equus caballus). Significant negative
      relationships between dietary CF and aD OM were obtained, but the significant
      difference in digestive efficiency between rabbits and guinea pigs (Cavia
      porcellus) reported from studies where both species had been investigated under
      identical conditions were not detectable in the larger data collection. However,
      the 95% confidence interval of the negative slope of the CF-aD OM relationship
      did not overlap between domestic horses on the one hand, and rabbits and guinea
      pigs on the other hand, indicating a less depressing effect of CF in horses.
      Akaike's information criterion indicated that aD of a macromineral did not only
      depend on its concentration in the diet, but also on the individual and various
      other diet characteristics and the presence of other macrominerals, indicating
      complex interactions. The data indicate similar mechanisms in the absorption of
      macrominerals amongst rabbits, rodents and horses, with the exception of Na and K
      in guinea pigs and Ca in chinchillas (Chinchilla laniger) that should be further
      corroborated. In particular, the occurrence of high aD Ca in hindgut fermenters,
      regardless of whether they employ a digestive strategy of coprophagy or whether
      they have fossorial habits, suggests that this peculiarity might represent an
      adaptation to hindgut fermentation in general. 

PMID- 25857397
TI  - Simple Partial Status Epilepticus One-day Post Single-pulse TMS to the Affected
      Hemisphere in a Participant With Chronic Stroke.

PMID- 25857398
TI  - Cathodal Transcranial Direct Current Stimulation Over Left Dorsolateral
      Prefrontal Cortex Area Promotes Implicit Motor Learning in a Golf Putting Task.
AB  - BACKGROUND: Implicit motor learning is characterized by low dependence on working
      memory and stable performance despite stress, fatigue, or multi-tasking. However,
      current paradigms for implicit motor learning are based on behavioral
      interventions that are often task-specific and limited when applied in practice.
      OBJECTIVE: To investigate whether cathodal transcranial direct current
      stimulation (tDCS) over the left dorsolateral prefrontal cortex (DLPFC) area
      during motor learning suppressed working memory activity and reduced explicit
      verbal-analytical involvement in movement control, thereby promoting implicit
      motor learning. METHODS: Twenty-seven healthy individuals practiced a golf
      putting task during a Training Phase while receiving either real cathodal tDCS
      stimulation over the left DLPFC area or sham stimulation. Their performance was
      assessed during a Test phase on another day. Verbal working memory capacity was
      assessed before and after the Training Phase, and before the Test Phase. RESULTS:
      Compared to sham stimulation, real stimulation suppressed verbal working memory
      activity after the Training Phase, but enhanced golf putting performance during
      the Training Phase and the Test Phase, especially when participants were required
      to multi-task. CONCLUSION: Cathodal tDCS over the left DLPFC may foster implicit
      motor learning and performance in complex real-life motor tasks that occur during
      sports, surgery or motor rehabilitation.

PMID- 25857399
TI  - Solvent-dependent strong asymmetric amplification in the catalytic
      enantioselective Henry reaction using the trans-N,N'-bis-biphenyl-4-ylmethyl
      cyclohexane-1,2-diamine-CuCl2 complex.
AB  - A strong asymmetric amplification was observed in the enantioselective Henry
      reaction catalyzed by the (R,R)-trans-N,N'-bis-biphenyl-4-ylmethyl-cyclohexane
      1,2-diamine.CuCl2 complex in AcOEt, while no amplification occurred in MeOH. 

PMID- 25857400
TI  - Simultaneous determination of arbutin and its decomposed product hydroquinone in
      whitening creams using high-performance liquid chromatography with photodiode
      array detection: Effect of temperature and pH on decomposition.
AB  - OBJECTIVE: Arbutin is an effective agent for the treatment of melanin disorders.
      Arbutin may be converted to hydroquinone under conditions of high temperature,
      ultraviolet (UV) radiation and dilute acid. The aim of the current study was to
      develop an analytical method to determine the levels of arbutin and hydroquinone
      in whitening cosmetic products using high-performance liquid chromatography with
      photodiode array detection (HPLC-DAD). In addition, we investigated the effects
      of high temperature and pH on the decomposition of arbutin. METHODS: Samples
      extracted using two-step sonications were separated on a C18 column using a
      gradient mobile phase consisting of water and methanol. A 60-mm (40 MUL) DAD cell
      was used to enhance the sensitivity of hydroquinone determination. Thermal
      decomposition of arbutin was evaluated at temperatures ranging from 60 to 120
      degrees C for 1-36 h. RESULTS: The method showed good linearity (R(2) >= 0.9997),
      precision (relative standard deviation, RSD < 5%) and acceptable extraction
      recovery (90-102.6%). The limits of quantitation for arbutin and hydroquinone
      were 0.0085 and 0.0119 MUg mL(-1) , respectively. One sample of 21 cosmetic
      products tested contained arbutin at a concentration 1.61 g 100 g(-1) cream and
      0.12 g 100 g(-1) cream of hydroquinone. Arbutin (327.18 ppm) decomposed after 6 h
      at 120 degrees C and produced 10.73 ppm of hydroquinone. CONCLUSION: The
      developed method is simple to detect both arbutin and hydroquinone simultaneously
      in cosmetic products, at an adequate level of sensitivity. Notably, temperature
      and pH did not influence the decomposition of arbutin to hydroquinone in a 2%
      arbutin cream.

PMID- 25857401
TI  - Angiographic characteristics of intermediate stenosis of the left anterior
      descending artery for determination of lesion significance as identified by
      fractional flow reserve.
AB  - Previous studies have shown a poor correlation between angiographic assessment of
      stenosis grade (%) and its functional assessment by fractional flow reserve
      (FFR). This study aimed to investigate whether a more comprehensive evaluation of
      the coronary angiogram may contribute to a better identification of flow-limiting
      stenoses. Coronary angiograms of 1,350 patients (1,883 lesions) were
      retrospectively analyzed for stenosis grade (eyeballing, %) and matched with FFR
      values. Angiography-derived optimal cut-off values and intervals delineating the
      [90% sensitivity-90% specificity] range were 50.8% [42.5-65.0%] for the left main
      (LM), 62.2% [50.0-72.5%] for the proximal (prox)/mid left anterior descending
      (LAD) artery, 66.3% [57.5-77.5%] for the prox/mid right coronary artery (RCA),
      70.5% [60.0-80.0%] for the prox left circumflex/first obtuse marginal (LCX/OM1),
      and 71.4% [62.5-82.5%] for the more distal segments. In patients with
      intermediate LAD lesions, 5 angiographic parameters were identified as
      independent predictors of flow limitation: (1) a 30-50% lesion prox to the lesion
      of interest, (2) lesion length >20 mm, (3) distal take-off of all diagonal
      branches >=2 mm diameter, (4) "apical wrap" of LAD, and (5) collaterals to an
      occluded LCX/RCA. Based on these results, a risk score (P20-DAC2) for prediction
      of flow limitation in intermediate LAD lesions was derived. In conclusion, a
      comprehensive evaluation of the coronary angiogram-in which besides stenosis
      grade also other lesion/vessel characteristics are evaluated-can lead to a more
      accurate identification of functionally significant coronary stenoses. 

PMID- 25857402
TI  - Multinuclear metal-binding ability of a carotene.
AB  - Carotenes are naturally abundant unsaturated hydrocarbon pigments, and their
      fascinating physical and chemical properties have been studied intensively not
      only for better understanding of the roles in biological processes but also for
      the use in artificial chemical systems. However, their metal-binding ability has
      been virtually unexplored. Here we report that beta-carotene has the ability to
      assemble and align ten metal atoms to afford decanuclear homo- and heterometal
      chain complexes. The metallo-carotenoid framework shows reversible metalation
      demetalation reactivity with multiple metals, which allows us to control the size
      of metal chains as well as the heterobimetallic composition and arrangement of
      the carotene-supported metal chains. 

PMID- 25857403
TI  - Profile analyses of the Personality Assessment Inventory following military
      related traumatic brain injury.
AB  - Personality Assessment Inventory (PAI) profiles were examined in 160 U.S. service
      members (SMs) following mild-severe traumatic brain injury (TBI). Participants
      who sustained a mild TBI had significantly higher PAI scores than those with
      moderate-severe TBI on eight of the nine clinical scales examined. A two-step
      cluster analysis identified four PAI profiles, heuristically labeled "High
      Distress", "Moderate Distress", "Somatic Distress," and "No Distress".
      Postconcussive and posttraumatic stress symptom severity was highest for the High
      Distress group, followed by the Somatic and Moderate Distress groups, and the No
      Distress group. Profile groups differed in age, ethnicity, rank, and TBI
      severity. Findings indicate that meaningful patterns of behavioral and
      personality characteristics can be detected in active duty military SMs following
      TBI, which may prove useful in selecting the most efficacious rehabilitation
      strategies.

PMID- 25857404
TI  - Incidental learning during rapid information processing on the symbol-digit
      modalities test.
AB  - The Symbol--Digit Modalities Test (SDMT) is widely used to assess processing
      speed in MS patients. We developed a computerized version of the SDMT (c-SDMT)
      that scored participants' performance during subintervals over the course of the
      usual 90-s time period and also added an incidental learning test (c-ILT) to
      assess how well participants learned the symbol-digit associations while
      completing the c-SDMT. Patients with MS (n = 65) achieved lower scores than
      healthy controls (n = 38) on both the c-SDMT and c-ILT, and the scores on the two
      tests were correlated. However, no increase in the rate of item completion
      occurred for either group over the course of the c-SDMT, and the difference
      between groups was the same during each subinterval. Therefore, it seems
      implausible that controls completed more items on the c-SDMT because they were
      more adept at learning the symbol-digit associations as the test ensued. Instead,
      MS patients' poorer incidental learning performance appears to reflect the
      greater attentional burden that tasks requiring rapid serial processing of
      information impose upon them. 

PMID- 25857405
TI  - Core-Cross-Linking Accelerates Antitumor Activities of Paclitaxel-Conjugate
      Micelles to Prostate Multicellular Tumor Spheroids: A Comparison of 2D and 3D
      Models.
AB  - The 2D monolayer cell culture model is often the first step in the prediction of
      the success or failure of a nanoparticle-based drug delivery system. However,
      there is often poor translation between the 2D monolayer in vitro results and the
      nanoparticle-drug performance in vivo. One possible way of bridging this gap is
      the use of multicellular tumor spheroids (MCTSs) as an intermediate in vitro
      model due to its 3D structure. This paper aims to quantify and compare the
      results obtained from traditional 2D monolayer cell cultures and 3D MCTS by
      studying the cytotoxic effects of free paclitaxel (PTX) and paclitaxel, which has
      been conjugated to a poly(ethylene glycol methyl ether acrylate)-b
      poly(carboxyethyl acrylate) (POEGMEA-b-PCEA-PTX) block copolymer and self
      assembled to give a micellar delivery system. The core of the micelle was cross
      linked with a diamino nondegradable cross-linker to compare the effects of
      micelle stability on the results. Although the 2D prostate tumor cell culture
      results indicated that all micellar variants (IC50: 193-271 nM) were
      significantly less toxic than free paclitaxel (IC50: 15.2 nM), the micelles
      showed faster and higher cytotoxicity than free PTX in the 3D prostate MCTS. The
      cross-linking of micelles even showed accelerated antitumor activities to the
      MCTS compared with un-cross-linked micelles. The results indicate that DAO-cross
      linked POEGMEA-b-PCEA-PTX conjugate micelles will be a useful nanodrug carrier
      for prostate cancer therapy. MCTS offers a very promising method of incorporating
      3D structures into in vitro testing. 

PMID- 25857406
TI  - MiR-218 mediates tumorigenesis and metastasis: Perspectives and implications.
AB  - MicroRNAs (miRNAs) are a class of small non-coding RNAs that negatively regulate
      gene expression at the post-transcriptional level. As a highly conserved miRNA
      across a variety of species, microRNA-218 (miR-218) was found to play pivotal
      roles in tumorigenesis and progression. A group of evidence has demonstrated that
      miR-218 acts as a tumor suppressor by targeting many oncogenes related to
      proliferation, apoptosis and invasion. In this review, we provide a complex
      overview of miR-218, including its regulatory mechanisms, known functions in
      cancer and future challenges as a potential therapeutic target in human cancers. 

PMID- 25857408
TI  - Assessment of radical scavenging capacity of antioxidants contained in foods and
      beverages in plasma solution.
AB  - The assessment of the radical scavenging capacity of antioxidants has been the
      subject of extensive studies and controversy. The aim of this study is to develop
      a simple and inexpensive method for the assessment of the radical scavenging
      capacity of antioxidants contained in foods and beverages in plasma solution, a
      biologically relevant heterogeneous medium. Three types of probes, hydrophilic
      pyranine, with low reactivity, hydrophilic pyrogallol red (PGR), with high
      reactivity, and lipophilic BODIPY, with moderate reactivity, were separately used
      to measure the amount and rate of peroxyl radical scavenging. The amount of
      radicals scavenged by antioxidants was assessed from the lag phase produced by
      antioxidants in the decay of pyranine and BODIPY, while the reactivity of the
      antioxidants was assessed from their effect on the decay rate of PGR. Two liquid
      and two solid samples were tested. Commercial bottled green tea and vegetable
      juice were found to scavenge 15.6 and 3.45 mmol radicals L(-1) and the former
      scavenged peroxyl radicals 81 times faster than the latter. As for the solid
      samples, instant coffee powder was found to scavenge several times more radicals
      and more rapidly than green tea powder. This method may be applied to the
      assessment of the radical scavenging capacity of antioxidants contained in foods,
      beverages, and supplements in biologically relevant heterogeneous media. 

PMID- 25857407
TI  - Htr2a Expression Responds Rapidly to Environmental Stimuli in an Egr3-Dependent
      Manner.
AB  - Pharmacologic and genetic findings have implicated the serotonin 2A receptor (5
      HT2AR) in the etiology of schizophrenia. Recent studies have shown reduced 5
      HT2AR levels in schizophrenia patients, yet the cause of this difference is
      unknown. Environmental factors, such as stress, also influence schizophrenia
      risk, yet little is known about how environment may affect this receptor. To
      determine if acute stress alters 5-HT2AR expression, we examined the effect of
      sleep deprivation on cortical Htr2a mRNA in mice. We found that 6 h of sleep
      deprivation induces a twofold increase in Htr2a mRNA, a more rapid effect than
      has been previously reported. This effect requires the immediate early gene early
      growth response 3 (Egr3), as sleep deprivation failed to induce Htr2a expression
      in Egr3-/- mice. These findings provide a functional link between two
      schizophrenia candidate genes and an explanation of how environment may influence
      a genetic predisposition for schizophrenia. 

PMID- 25857411
TI  - Effect of ultrasound on the diffusion properties of casein entrapped in alginate
      chitosan gel.
AB  - The effects of ultrasound-assisted and pre-ultrasound treatment on the diffusion
      properties of casein imbedded by alginate-chitosan gel were investigated. The
      fluorescence spectrophotometry for determining the fluorescence intensity of
      casein was established to calculate the diffusion coefficient (De). Scanning
      electron microscope (SEM) was used to observe the microstructure of gel beads.
      The results showed that two different kinds of ultrasonic treatments had obvious
      distinctions on the casein diffusion. As the frequency increased, the value of De
      decreased from 28.56 * 10(-4)m(2)s(-1) (28 kHz) to 2.57 * 10(-4)m(2)s(-1) (135
      kHz) during the ultrasound-assisted process. While, the minimum De of 8.6 * 10(
      4)m(2)s(-1) was achieved at the frequency of 50 kHz for the pre-ultrasound
      treatment. The impact of power on the diffusion showed that De increased with the
      increase of ultrasound power until it reached the highest value 28.56 * 10(
      4)m(2)s(-1) (0.45 W/cm(2)) in the ultrasound-assisted process. It would reach the
      maximum value (16 * 10(-4)m(2)s(-1)) when the power was 0.25 W/cm(2) in the
      pretreatment ultrasound process. SEM analysis exhibited that the gel structural
      changes (area ratio) were in accordance with De through different ultrasonic
      treatment. This was mainly due to the mechanical action and cavitation of the
      ultrasonic treatment. This study is important to explain the diffusion properties
      of large molecules and explore the mechanism of enzyme immobilization treated by
      ultrasound.

PMID- 25857410
TI  - Cell lineage branching as a strategy for proliferative control.
AB  - BACKGROUND: How tissue and organ sizes are specified is one of the great unsolved
      mysteries in biology. Experiments and mathematical modeling implicate feedback
      control of cell lineage progression, but a broad understanding of what lineage
      feedback accomplishes is lacking. RESULTS: By exploring the possible effects of
      various biologically relevant disturbances on the dynamic and steady state
      behaviors of stem cell lineages, we find that the simplest and most frequently
      studied form of lineage feedback - which we term renewal control - suffers from
      several serious drawbacks. These reflect fundamental performance limits dictated
      by universal conservation-type laws, and are independent of parameter choice.
      Here we show that introducing lineage branches can circumvent all such
      limitations, permitting effective attenuation of a wide range of perturbations.
      The type of feedback that achieves such performance - which we term fate control 
      involves promotion of lineage branching at the expense of both renewal and
      (primary) differentiation. We discuss the evidence that feedback of just this
      type occurs in vivo, and plays a role in tissue growth control. CONCLUSIONS:
      Regulated lineage branching is an effective strategy for dealing with
      disturbances in stem cell systems. The existence of this strategy provides a
      dynamics-based justification for feedback control of cell fate in vivo.

PMID- 25857412
TI  - Value of a Lower-Limb Immobilization Device for Optimization of SPECT/CT Image
      Fusion.
AB  - The foot and the ankle are small structures commonly affected by disorders, and
      their complex anatomy represents a significant diagnostic challenge. By providing
      information on anatomic and bone structure that cannot be obtained from
      functional imaging, SPECT/CT image fusion can be particularly useful in
      increasing diagnostic certainty about bone pathology. However, because of the
      lengthy duration of a SPECT acquisition, a patient's involuntary movements may
      lead to misalignment between SPECT and CT images. Patient motion can be reduced
      using a dedicated patient support. We designed an ankle- and foot-immobilizing
      device and measured its efficacy at improving image fusion. METHODS: We enrolled
      20 patients who underwent SPECT/CT of the ankle and foot with and without a foot
      support. The misalignment between SPECT and CT images was computed by manually
      measuring 14 fiducial markers chosen among anatomic landmarks also visible on
      bone scintigraphy. ANOVA was performed for statistical analysis. RESULTS: The
      absolute average difference without and with support was 5.1 +/- 5.2 mm (mean +/-
      SD) and 3.1 +/- 2.7 mm, respectively, which is significant (P < 0.001).
      CONCLUSION: The introduction of the foot support significantly decreased
      misalignment between SPECT and CT images, which may have a positive clinical
      influence in the precise localization of foot and ankle pathology.

PMID- 25857414
TI  - Medical isotope crisis.

PMID- 25857413
TI  - Hepatobiliary Iminodiacetic Acid Scanning Detects High-Grade Biliary Obstruction
      Secondary to IgG4-Related Sclerosing Cholangitis.
AB  - In this report, we present a case of high-grade biliary obstruction discovered on
      hepatobiliary scintigraphy secondary to IgG4-related sclerosing cholangitis with
      concomitant autoimmune pancreatitis, a recently described entity that is gaining
      recognition in the radiology literature. To our knowledge, the scintigraphic
      findings have yet to be described in the literature. We present the hepatobiliary
      scintigraphic findings and their correlation to findings on endoscopic retrograde
      cholangiopancreatography, CT, and MR cholangiopancreatography, with posttreatment
      follow-up imaging. IgG4-related sclerosing cholangitis is a rare yet important
      diagnostic consideration when high-grade obstruction is seen on hepatobiliary
      iminodiacetic acid scanning. We discuss the differential diagnosis of high-grade
      biliary obstruction seen on hepatobiliary iminodiacetic acid scanning. 

PMID- 25857415
TI  - Plaque Inflammation Imaging in Severe Carotid Stenosis and Recurrent Cerebral
      Ischemia.
AB  - A strong relationship exists between the severity of carotid stenosis and early
      stroke risk. Inflammation is believed to be an important event for
      atherosclerotic plaque destabilization and subsequent thromboembolism. (18)F-FDG
      can image atherosclerotic inflammation, providing information about plaque
      biology, which may serve as a useful biomarker for the assessment of early stroke
      risk. 

PMID- 25857409
TI  - Refined histopathological predictors of BRCA1 and BRCA2 mutation status: a large
      scale analysis of breast cancer characteristics from the BCAC, CIMBA, and ENIGMA
      consortia.
AB  - INTRODUCTION: The distribution of histopathological features of invasive breast
      tumors in BRCA1 or BRCA2 germline mutation carriers differs from that of
      individuals with no known mutation. Histopathological features thus have utility
      for mutation prediction, including statistical modeling to assess pathogenicity
      of BRCA1 or BRCA2 variants of uncertain clinical significance. We analyzed large
      pathology datasets accrued by the Consortium of Investigators of Modifiers of
      BRCA1/2 (CIMBA) and the Breast Cancer Association Consortium (BCAC) to reassess
      histopathological predictors of BRCA1 and BRCA2 mutation status, and provide
      robust likelihood ratio (LR) estimates for statistical modeling. METHODS:
      Selection criteria for study/center inclusion were estrogen receptor (ER) status
      or grade data available for invasive breast cancer diagnosed younger than 70
      years. The dataset included 4,477 BRCA1 mutation carriers, 2,565 BRCA2 mutation
      carriers, and 47,565 BCAC breast cancer cases. Country-stratified estimates of
      the likelihood of mutation status by histopathological markers were derived using
      a Mantel-Haenszel approach. RESULTS: ER-positive phenotype negatively predicted
      BRCA1 mutation status, irrespective of grade (LRs from 0.08 to 0.90). ER-negative
      grade 3 histopathology was more predictive of positive BRCA1 mutation status in
      women 50 years or older (LR = 4.13 (3.70 to 4.62)) versus younger than 50 years
      (LR = 3.16 (2.96 to 3.37)). For BRCA2, ER-positive grade 3 phenotype modestly
      predicted positive mutation status irrespective of age (LR = 1.7-fold), whereas
      ER-negative grade 3 features modestly predicted positive mutation status at 50
      years or older (LR = 1.54 (1.27 to 1.88)). Triple-negative tumor status was
      highly predictive of BRCA1 mutation status for women younger than 50 years (LR =
      3.73 (3.43 to 4.05)) and 50 years or older (LR = 4.41 (3.86 to 5.04)), and
      modestly predictive of positive BRCA2 mutation status in women 50 years or older
      (LR = 1.79 (1.42 to 2.24)). CONCLUSIONS: These results refine likelihood-ratio
      estimates for predicting BRCA1 and BRCA2 mutation status by using commonly
      measured histopathological features. Age at diagnosis is an important variable
      for most analyses, and grade is more informative than ER status for BRCA2
      mutation carrier prediction. The estimates will improve BRCA1 and BRCA2 variant
      classification and inform patient mutation testing and clinical management.

PMID- 25857416
TI  - A student perspective on a data acquisition project.

PMID- 25857417
TI  - PET/CT for Pancreatic Malignancy: Potential and Pitfalls.
AB  - Pancreatic malignancy carries a poor prognosis and is the fourth leading cause of
      cancer-related deaths in the United States. Although conventional imaging with CT
      and MR remains the main imaging modality, recent times have seen an increase in
      the applications of PET/CT in the evaluation of pancreatic malignancy. Newer data
      are becoming available, highlighting the advantages, limitations, and pitfalls in
      PET/CT imaging of the pancreas. This article highlights the applications of
      PET/CT in various stages of management of pancreatic malignancy and compares
      these with conventional imaging with CT and MR. 

PMID- 25857418
TI  - Liquid gastric emptying as an adjunct to hepatobiliary scintigraphy when oral
      corn oil is used as a cholecystagogue for determining gallbladder emptying.
AB  - During times of sincalide shortage, a fatty meal can be used to stimulate
      gallbladder contraction during hepatobiliary scintigraphy. However, if a patient
      has an abnormal gallbladder ejection fraction (GBEF), is the cause chronic
      cholecystitis or is it inadequate cholecystokinin stimulation due to poor gastric
      emptying? Hence, during the 2014 sincalide shortage, simultaneous liquid gastric
      emptying using (99m)Tc-sulfur colloid along with corn oil emulsion was initiated
      as routine practice in patients evaluated for GBEF. The objective of this study
      was to retrospectively assess the time course of gastric emptying in these
      patients, especially with regard to whether delayed gastric emptying may be a
      factor in some patients with a poor GBEF. METHODS: My institution's clinical
      imaging procedure during the 2014 sincalide shortage consisted of routine (99m)Tc
      mebrofenin hepatobiliary scintigraphy followed by corn oil emulsion and (99m)Tc
      sulfur colloid orally. Dynamic imaging with regions of interest encompassing the
      gallbladder and the stomach allowed determination of GBEF and gastric emptying.
      For this study, the imaging records for 53 consecutive patients undergoing this
      clinical procedure were reviewed. The time for half gastric emptying, along with
      percentage gastric emptying at the end of imaging, was evaluated in relationship
      to GBEF. RESULTS: Seventeen patients had a normal GBEF (74% +/- 14%) and
      satisfactory gastric emptying (31 +/- 21 min for half emptying, 75% +/- 14%
      emptying at end of imaging); 17 patients had a normal GBEF (77% +/- 17%) despite
      unsatisfactory gastric emptying (only 30% +/- 14% emptying at end of imaging); 5
      patients had an abnormal GBEF (19% +/- 9%) and satisfactory gastric emptying (26
      +/- 19 min for half emptying, 82% +/- 14% emptying at end of imaging), supporting
      a diagnosis of chronic cholecystitis; 11 patients had an abnormal GBEF (26% +/-
      9%) but also unsatisfactory gastric emptying (only 26% +/- 13% emptying at end of
      imaging), which did offer additional support for a diagnosis of chronic
      cholecystitis; and 3 patients had a borderline GBEF (40% +/- 2%) with
      satisfactory gastric emptying (59% +/- 6% emptying at end of imaging).
      CONCLUSION: Simultaneous liquid gastric emptying can provide additional
      information in the interpretation of GBEF when a fatty meal is used as an oral
      cholecystagogue, especially to help differentiate chronic cholecystitis from
      inadequate cholecystokinin stimulation due to poor gastric emptying.

PMID- 25857419
TI  - Reply: Medical isotope crisis.

PMID- 25857420
TI  - Oncocytic Adenoma of Thyroid Incidentally Detected by 18F-Fluorocholine PET/CT.
AB  - A 58-old-man underwent (18)F-fluorocholine PET/CT for restaging of prostate
      cancer because of a rising level of prostate-specific antigen.( 18)F
      fluorocholine showed no significant tracer uptake at the site of the
      prostatectomy or the pelvic lymph nodes. Incidental high tracer uptake was
      observed in a 26 * 23 mm left thyroid nodule. A benign tumor of the thyroid
      (oncocytic adenoma of thyroid) was diagnosed after left loboisthmectomy.

PMID- 25857421
TI  - A comparative study of leachate quality and biogas generation in simulated
      anaerobic and hybrid bioreactors.
AB  - Research has been conducted to compare leachate characterization and biogas
      generation in simulated anaerobic and hybrid bioreactor landfills with typical
      Chinese municipal solid waste (MSW). Three laboratory-scale reactors, an
      anaerobic (A1) and two hybrid bioreactors (C1 and C2), were constructed and
      operated for about 10months. The hybrid bioreactors were operated in an aerobic
      anaerobic mode with different aeration frequencies by providing air into the
      upper layer of waste. Results showed that the temporary aeration into the upper
      layer aided methane generation by shortening the initial acidogenic phase because
      of volatile fatty acids (VFAs) reduction and pH increase. Chemical oxygen demand
      (COD) decreased faster in the hybrid bioreactors, but the concentrations of
      ammonia-nitrogen in the hybrid bioreactors were greater than those in the
      anaerobic control. Methanogenic conditions were established within 75d and 60d in
      C1 and C2, respectively. However, high aeration frequency led to the consumption
      of organic matters by aerobic degradation and resulted in reducing accumulative
      methane volume. The temporary aeration enhanced waste settlement and the
      settlement increased with increasing the frequency of aeration. Methane
      production was inhibited in the anaerobic control; however, the total methane
      generations from hybrid bioreactors were 133.4L/kgvs and 113.2L/kgvs. As for MSW
      with high content of food waste, leachate recirculation right after aeration
      stopped was not recommended due to VFA inhibition for methanogens. 

PMID- 25857422
TI  - Innovative test method for the estimation of the foaming tendency of substrates
      for biogas plants.
AB  - Excessive foaming in anaerobic digestion occurs at many biogas plants and can
      cause problems including plugged gas pipes. Unfortunately, the majority of biogas
      plant operators are unable to identify the causes of foaming in their biogas
      reactor. The occurrence of foaming is often related to the chemical composition
      of substrates fed to the reactor. The consistency of the digestate itself is also
      a crucial part of the foam formation process. Thus, no specific recommendations
      concerning substrates can be given in order to prevent foam formation in biogas
      plants. The safest way to avoid foaming is to test the foaming tendency of
      substrates on-site. A possible solution is offered by an innovative foaming test.
      With the help of this tool, biogas plant operators can evaluate the foaming
      disposition of new substrates prior to use in order to adjust the composition of
      substrate mixes. 

PMID- 25857423
TI  - Factors affecting postoperative outcome in otosclerosis patients: Predictive role
      of audiological and clinical features.
AB  - OBJECTIVE: Factors affecting postoperative hearing results of patients with
      otosclerosis were analyzed. METHODS: Included were 191 patients with otosclerosis
      in whom 234 primary stapes surgeries were performed from August 1991 to December
      2011 by one surgeon in three tertiary hospitals. Evaluation of factors affecting
      postoperative hearing thresholds at individual frequencies were performed by
      logistic regression analysis. RESULTS: Closure of the air-bone gap (ABG) after
      surgery was good at 2kHz, but poor at 4kHz and frequencies under 1kHz. In
      addition, improvement at 8kHz was worse than that at any other frequency.
      Multivariate logistic regression analysis by the stepwise method showed that
      under the mean preoperative ABG (odds ratio [OR]=2.42), unilaterality (OR=2.53)
      and male sex (OR=2.65) were significantly better prognostic factors at 250Hz. At
      500Hz, under mean preoperative ABG (OR=2.56) was the significantly better factor.
      No significant factors were found at 1kHz. Cochlear otosclerosis (OR=3.57) was a
      significantly worse prognostic factor at 2kHz. Under mean preoperative ABG
      (OR=2.82) and younger age (OR=1.03) were significantly better prognostic factors
      at 4kHz. At 8kHz, worse preoperative air conduction threshold (OR=1.96) was a
      significantly better prognostic factor. CONCLUSION: Preoperative ABG,
      preoperative air conduction threshold, cochlear otosclerosis, male sex,
      laterality and age were significant prognostic factors for postoperative hearing
      outcome in otosclerosis patients. Especially, preoperative ABG was a significant
      prognostic factor at multiple frequencies. We suppose that patients with larger
      preoperative ABG have some other otosclerotic lesions outside the oval window
      niche.

PMID- 25857424
TI  - Cognitive decline after cardiac arrest--It is more to the picture than hypoxic
      brain injury.

PMID- 25857425
TI  - Studies on the synthesis, stability and conformation of 2-sulfonyl-oxetane
      fragments.
AB  - 2-(Arylsulfonyl)oxetanes have been prepared as new structural motifs of interest
      for medicinal chemistry. These are designed to fit within fragment space and be
      suitable for screening in fragment based drug discovery, as well as being
      suitable for further elaboration or incorporation into drug-like compounds. The
      oxetane ring is constructed through an efficient C-C bond forming cyclisation
      which allows the incorporation of a wide range of aryl-sulfonyl groups.
      Furthermore, biaryl-containing compounds can be accessed through Suzuki-Miyaura
      coupling from halogenated derivatives. With a number of oxetane containing
      fragment compounds available, their pH stability was assessed, indicating good
      half-life values for mono-substituted aryl sulfonyl oxetanes across the pH range
      (1 to 10). Solubility and metabolic stability data is also reported. Finally, the
      conformation of the fragments is assessed computationally, providing an
      indication of possible binding orientations. 

PMID- 25857426
TI  - Electronic cigarette use and harm reversal: emerging evidence in the lung.
AB  - Electronic cigarettes (ECs) have been rapidly gaining ground on conventional
      cigarettes due to their efficiency in ceasing or reducing tobacco consumption,
      competitive prices, and the perception of them being a much less harmful smoking
      alternative. Direct confirmation that long-term EC use leads to reductions in
      smoking-related diseases is not available and it will take a few decades before
      the tobacco harm reduction potential of this products is firmly established.
      Nonetheless, it is feasible to detect early changes in airway function and
      respiratory symptoms in smokers switching to e-vapor. Acute investigations do not
      appear to support negative respiratory health outcomes in EC users and initial
      findings from long-term studies are supportive of a beneficial effect of EC use
      in relation to respiratory outcomes. The emerging evidence that EC use can
      reverse harm from tobacco smoking should be taken into consideration by
      regulatory authorities seeking to adopt proportional measures for the e-vapor
      category. 

PMID- 25857427
TI  - Chronic disease causes more visits to emergency departments while visits for
      injuries fall, US study finds.

PMID- 25857428
TI  - Continuous High-Frequency Stimulation of the Subthalamic Nucleus Improves Cell
      Survival and Functional Recovery Following Dopaminergic Cell Transplantation in
      Rodents.
AB  - Subthalamic nucleus (STN) high-frequency stimulation (HFS) is a routine treatment
      in Parkinson's disease (PD), with confirmed long-term benefits. An alternative,
      but still experimental, treatment is cell replacement and restorative therapy
      based on transplanted dopaminergic neurons. The current experiment evaluated the
      potential synergy between neuromodulation and grafting by studying the effect of
      continuous STN-HFS on the survival, integration, and functional efficacy of
      ventral mesencephalic dopaminergic precursors transplanted into a unilateral 6
      hydroxydopamine medial forebrain bundle lesioned rodent PD model. One group
      received continuous HFS of the ipsilateral STN starting a week prior to
      intrastriatal dopaminergic neuron transplantation, whereas the sham-stimulated
      group did not receive STN-HFS but only dopaminergic grafts. A control group was
      neither lesioned nor transplanted. Over the following 7 weeks, the animals were
      probed on a series of behavioral tasks to evaluate possible graft and/or
      stimulation-induced functional effects. Behavioral and histological data suggest
      that STN-HFS significantly increased graft cell survival, graft-host integration,
      and functional recovery. These findings might open an unexplored road toward
      combining neuromodulative and neuroregenerative strategies to treat severe
      neurologic conditions. 

PMID- 25857429
TI  - Tip lesion variant of primary focal and segmental glomerulosclerosis:
      clinicopathological analysis of 20 cases.
AB  - The glomerular tip lesion (GTL) is a distinctive histopathologic lesion which is
      regarded as a variant of focal and segmental glomerulosclerosis (FSGS). The
      prognostic significance of GTL among other FSGS variants has been disputed. In
      order to define the clinical features and outcome of GTL, we retrospectively
      reviewed the presenting clinical features, laboratory and biopsy findings and
      surveillance in our cohort of GTL, which consisted of 20 adults with native
      kidneys (mean age 46 years) with follow-up data ranging from 3 to 137 months. At
      presentation, mean urine protein, serum albumin and cholesterol levels were 5.17
      g/d, 2.6 g/dL and 312.9 mg/dL, respectively, and none had renal insufficiency.
      Microscopic hematuria was detected in five patients. At biopsy, glomerular
      segmental lesions consisted of GTL without perihilar or collapsing lesions. GTL
      was observed in a variable proportion of glomeruli from 2.6% to 100%. Mesangial
      proliferation was seen in nine cases, at a moderate degree in two and mild in the
      rest. Three biopsies showed mild, two showed moderate interstitial
      fibrosis/tubular atrophy. Eleven patients received steroids alone and eight
      received sequential therapy with steroids and a cytotoxic agent. At a mean follow
      up of 40.6 months, 17 patients (85%) achieved complete remission of nephrotic
      syndrome, 15% had partial remission. Four of 17 suffered from recurrences. No
      patient progressed to end-stage renal disease. Serum albumin at diagnosis was the
      only predictor of a recurrence (p = 0.037). Microscopic hematuria correlated with
      incomplete remission (p = 0.045). Our study demonstrates a clearly favorable
      prognosis in patients with FSGS-GTL variant.

PMID- 25857430
TI  - SALINE ARTHROGRAPHY OF THE DISTAL INTERPHALANGEAL JOINT FOR LOW-FIELD MAGNETIC
      RESONANCE IMAGING OF THE EQUINE PODOTROCHLEAR BURSA: FEASIBILITY STUDY.
AB  - Abnormalities of the deep digital flexor tendon, navicular bone, and collateral
      sesamoidean ligament can be difficult to visualize using magnetic resonance
      imaging (MRI) if bursal fluid is absent. The use of saline podotrochlear
      bursography improves podotrochlear apparatus evaluation, however, the technique
      has disadvantages. The objective of this prospective feasibility study was to
      describe saline arthrography of the distal interphalangeal joint as an
      alternative technique for improving MRI visualization of the deep digital flexor
      tendon, navicular bone, collateral sesamoidean ligament, and podotrochlear bursa,
      and to compare this technique with saline podotrochlear bursography. Eight paired
      cadaver forelimbs were sampled. Saline podotrochlear bursography or saline
      arthrography techniques were randomly assigned to one limb, with the alternate
      technique performed on the contralateral limb. For precontrast and postcontrast
      studies using each technique, independent observers scored visualization of the
      dorsal aspect of the deep digital flexor tendon, palmar aspect of the navicular
      bone, collateral sesamoidean ligament, and podotrochlear bursa. Both contrast
      techniques improved visualization of structures over precontrast MR images and
      visualization scores for both techniques were similar. Findings from this study
      demonstrated that saline arthrography is feasible and comparable to saline
      podotrochlear bursography for producing podotrochlear bursa distension and
      separation of the structures of the podotrochlear apparatus on nonweight bearing
      limbs evaluated with low-field MRI. Clinical evaluation of saline arthrography on
      live animals is needed to determine if this technique is safe and effective as an
      alternative to saline podotrochlear bursography in horses with suspected
      pathology of the podotrochlear apparatus. 

PMID- 25857431
TI  - Estimating future energy use and CO2 emissions of the world's cities.
AB  - This paper develops a tool for estimating energy-related CO2 emissions from the
      world's cities based on regression models. The models are developed considering
      climatic (heating-degree-days) and urban design (land area per person)
      independent variables. The tool is applied on 3646 urban areas for estimating
      impacts on urban emissions of a) global transitioning to Electric Vehicles, b)
      urban density change and c) IPCC climate change scenarios. Results show that
      urban density decline can lead to significant increase in energy emissions (upto
      346% in electricity & 428% in transportation at 2% density decline by 2050).
      Among the IPCC climate scenarios tested, A1B is the most effective in reducing
      growth of emissions (upto 12% in electricity & 35% in heating). The tool can
      further be improved by including more data in the regression models along with
      inclusion of other relevant emissions and climatic variables. 

PMID- 25857432
TI  - Multistage aqueous two-phase extraction of a monoclonal antibody from cell
      supernatant.
AB  - This article presents results of continuous multistage aqueous two-phase
      extraction of an immunoglobulin G1 from cell supernatant in a mixer-settler unit.
      An aqueous two-phase system consisting of polyethylene glycol 2000, phosphate
      salt, and water was applied without and with sodium chloride (NaCl). Influences
      of different parameters such as throughput, phase ratio, and stage number on the
      extraction performance were analyzed. For systems without NaCl, the extraction
      was carried out as a washing step. An increase of stage number from one to five
      stages enabled to increase the immunoglobulin G1 purity from 11.8 to 32.6% at a
      yield of nearly 90%. Furthermore, a reduction of product phase volume due to a
      higher phase ratio led to an increase of purity from 20.8 to 29.6% in a three
      stage countercurrent extraction. For experiments with NaCl moderate partitioning
      conditions were adjusted by adding 8 wt% NaCl. In that case, the extraction was
      carried out as a stripping step.

PMID- 25857433
TI  - Diet, nutrients and metabolism: cogs in the wheel driving Alzheimer's disease
      pathology?
AB  - Alzheimer's disease (AD), the most common form of dementia, is a chronic,
      progressive neurodegenerative disease that manifests clinically as a slow global
      decline in cognitive function, including deterioration of memory, reasoning,
      abstraction, language and emotional stability, culminating in a patient with end
      stage disease, totally dependent on custodial care. With a global ageing
      population, it is predicted that there will be a marked increase in the number of
      people diagnosed with AD in the coming decades, making this a significant
      challenge to socio-economic policy and aged care. Global estimates put a direct
      cost for treating and caring for people with dementia at $US604 billion, an
      estimate that is expected to increase markedly. According to recent global
      statistics, there are 35.6 million dementia sufferers, the number of which is
      predicted to double every 20 years, unless strategies are implemented to reduce
      this burden. Currently, there is no cure for AD; while current therapies may
      temporarily ameliorate symptoms, death usually occurs approximately 8 years after
      diagnosis. A greater understanding of AD pathophysiology is paramount, and
      attention is now being directed to the discovery of biomarkers that may not only
      facilitate pre-symptomatic diagnosis, but also provide an insight into aberrant
      biochemical pathways that may reveal potential therapeutic targets, including
      nutritional ones. AD pathogenesis develops over many years before clinical
      symptoms appear, providing the opportunity to develop therapy that could slow or
      stop disease progression well before any clinical manifestation develops.

PMID- 25857434
TI  - Chemical analysis of the Chinese liquor Luzhoulaojiao by comprehensive two
      dimensional gas chromatography/time-of-flight mass spectrometry.
AB  - Luzhoulaojiao liquor is a type of Chinese liquor that dates back hundreds of
      years, but whose precise chemical composition remains unknown. This paper
      describes the screening of the liquor and the identification of its compounds
      using comprehensive two-dimensional gas chromatography/time-of-flight mass
      spectrometry (GC * GC/TOF-MS). Samples were prepared by both liquid-liquid
      extraction and solid-phase microextraction, which facilitated the detection of
      thousands of compounds in the liquor, thus demonstrating the superior performance
      of the proposed method over those reported in previous studies. A total of 320
      compounds were common to all 18 types of Luzhoulaojiao liquor studied here, and
      13 abundant and potentially bioactive compounds were further quantified. The
      results indicated that the high-performance method presented here is well suited
      for the detection and identification of compounds in liquors. This study also
      contributes to enriching our knowledge of the contents of Chinese liquors. 

PMID- 25857435
TI  - Liquid crystals for organic thin-film transistors.
AB  - Crystalline thin films of organic semiconductors are a good candidate for field
      effect transistor (FET) materials in printed electronics. However, there are
      currently two main problems, which are associated with inhomogeneity and poor
      thermal durability of these films. Here we report that liquid crystalline
      materials exhibiting a highly ordered liquid crystal phase of smectic E (SmE) can
      solve both these problems. We design a SmE liquid crystalline material, 2-decyl-7
      phenyl-[1]benzothieno[3,2-b][1]benzothiophene (Ph-BTBT-10), for FETs and
      synthesize it. This material provides uniform and molecularly flat
      polycrystalline thin films reproducibly when SmE precursor thin films are
      crystallized, and also exhibits high durability of films up to 200  degrees C. In
      addition, the mobility of FETs is dramatically enhanced by about one order of
      magnitude (over 10 cm(2) V(-1) s(-1)) after thermal annealing at 120  degrees C
      in bottom-gate-bottom-contact FETs. We anticipate the use of SmE liquid crystals
      in solution-processed FETs may help overcome upcoming difficulties with novel
      technologies for printed electronics. 

PMID- 25857436
TI  - Ferulic acid pretreatment mitigates MPTP-induced motor impairment and
      histopathological alterations in C57BL/6 mice.
AB  - CONTEXT: Ferulic acid (FA) is a potent ubiquitous plant antioxidant found in
      cereals such as brown rice, whole wheat, and oats. Phytochemical-based
      antioxidants are shown to be effective in neurodegenerative diseases. This study
      hypothesizes that supplementation of FA might combat oxidative stress-induced
      Parkinson's disease (PD). OBJECTIVE: To explore the effect of FA on 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP)-induced neurotoxicity.
      MATERIALS AND METHODS: Mice were randomized into five groups: Group I mice served
      as control. Group II mice received 5 * MPTP [25 mg/kg body weight (i.p.)] in
      saline 24 h apart starting from the 3rd day and continued till the last day of
      the experimental period of 7 d. In addition to MPTP injections, mice in Groups
      III, IV, and V were given FA at a dose of 20, 40, and 80 mg, respectively, for 7
      d. Mice were subjected to a battery of behavioral tests along with histological
      investigations. RESULTS: Our histological findings revealed that MPTP
      administration enhanced Bax/Bcl2 ratio and microglial cells activation reflecting
      induction of apoptosis and inflammation, respectively. This dopaminergic neuronal
      loss caused impairment in motor balance and coordination in MPTP mice as assessed
      by various behavioral tests. FA at a dose of 40 mg/kg/d body weight effectively
      attenuated MPTP-induced neurotoxicity. DISCUSSION: Antioxidant, free-radical
      quenching, and anti-inflammatory activities of FA could contribute to its
      neuroprotective effect. CONCLUSION: This study provides elementary evidence for
      the neuroprotective action of FA against MPTP-induced PD in mice and warrants
      further studies.

PMID- 25857437
TI  - Discovery of selective phosphatidylinositol 3-kinase inhibitors to treat
      hematological malignancies.
AB  - The phosphatidylinositol 3-kinase (PI3K) signaling pathway is associated with
      chemoresistance and poor prognosis of many cancers, including hematological
      malignancies (HM), such as leukemia, lymphomas, and multiple myeloma (MM).
      Targeting PI3K is emerging as a promising strategy in the treatment of these
      blood cancers. Recent approval of idelalisib, a specific inhibitor of PI3Kdelta,
      for the treatment of several types of HM, is likely to attract more interest in
      search for novel PI3K inhibitors. Here, we discuss classic and cutting-edge
      techniques and strategies to identify PI3K inhibitors for the treatment of HM.
      Each technique has its own strengths and limitations, and their combined
      application will accelerate the drug discovery process with fewer associated
      costs. 

PMID- 25857438
TI  - Shorter adult height is linked to raised risk of coronary artery disease, study
      shows.

PMID- 25857439
TI  - Toenail Onychomycosis-A Canadian Approach With a New Transungual Treatment:
      Development of a Clinical Pathway.
AB  - BACKGROUND: Onychomycosis is a difficult-to-treat infection whose current
      treatment paradigm relies primarily on oral antifungals. The emergence of new
      topical drugs broadens the therapeutic options and prompts a re-evaluation of the
      current Canadian treatment strategy. OBJECTIVE: To define a patient-centred
      Canadian treatment strategy for onychomycosis. METHODS: An expert panel of
      doctors who treat onychomycosis was convened. A systematic review of the
      literature on treatments for onychomycosis was conducted. Based on the results, a
      survey was designed to determine a consensus treatment system. RESULTS: First
      line therapy should be selected based on nail plate involvement, with terbinafine
      for severe onychomycosis (>60% involvement), terbinafine or efinaconazole for
      moderate onychomycosis (20%-60% involvement), and efinaconazole for mild
      onychomycosis (<20% involvement). Comorbidities, patient preference and
      adherence, or nail thickness may result in the use of alternative oral or topical
      antifungals. CONCLUSION: These guidelines allow healthcare providers and patients
      to make informed choices about preventing and treating onychomycosis.

PMID- 25857440
TI  - Functional disability and nursing resource use are predictive of antimicrobial
      resistance in nursing homes.
AB  - OBJECTIVES: To use a simple measure of activities of daily living, wounds, and
      indwelling devices (urinary catheter, feeding tube) to predict prevalent, new,
      and intermittent multidrug-resistant organism (MDRO) acquisition in nursing home
      (NH) residents. DESIGN: Secondary analysis, prospective cohort study. SETTING:
      Southeast Michigan NHs (n = 15). PARTICIPANTS: NH residents (N = 111, mean age
      81) with two or more monthly visits (729 total). MEASUREMENTS: Monthly
      microbiological surveillance for MDROs from multiple anatomic sites from
      enrollment until discharge or 1 year. The Arling scale, previously developed as a
      measure of NH residents' need (time-intensity) for nursing resources, was used to
      predict prevalent and time to new or intermittent acquisition (months) of
      methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant
      enterococci (VRE), and antibiotic-resistant gram-negative bacteria (R-GNB)
      colonization using multiple-failure accelerated time-factor survival analysis,
      controlling for comorbidity, hospitalization, and antibiotic use in the prior
      month. RESULTS: One-fifth of participants had a wound, and one-third had a
      device. There were 60 acquisitions of MRSA, 56 of R-GNB, and 15 of VRE. Expected
      time to acquisition was less than 1 year for MRSA (median 6.7 months) and R-GNB
      (median 4.5 months) and more than 1 year for VRE (median 40 months). Arling score
      was associated with earlier new MRSA and VRE acquisition. A resident with only
      mild functional impairment and no device or wound would be expected to acquire
      MRSA in 20 months, versus 5 months for someone needing the most-intense nursing
      contact. CONCLUSION: MDRO acquisition is common in community NHs. Need for
      nursing care predicts new MDRO acquisition in NHs, suggesting potential
      mechanisms for MDRO acquisition and strategies for future interventions for high
      risk individuals (e.g., enhanced barrier precautions).

PMID- 25857442
TI  - New insights into neutrophil and Leishmania infantum in vitro immune
      interactions.
AB  - The interaction between polymorphonuclear leukocytes (PMN) or neutrophils and
      Leishmania became an interesting focus of research, since PMN turn out to be
      essential cells in transiently hosting the parasites. This study aims to evaluate
      whether L. infantum, the etiological agent of zoonotic visceral leishmaniasis,
      influences the in vitro functional activity of murine neutrophils. Phagocytosis,
      chemotaxis, oxidative burst, degranulation and apoptosis assays were performed.
      Cytokines, chemokines and toll-like receptors gene expression were evaluated by
      Real-time PCR. Results indicate that some of the innate features of PMN immunity
      were activated when in contact with L. infantum. However, parasites might
      negatively interfere with PMN defense mechanisms compromising the link between
      innate and acquired immunity. This work provides additional insights on the
      inflammatory immune interactions between neutrophils and L. infantum highlighting
      the role of PMN in Leishmania infection. 

PMID- 25857441
TI  - Establishing pluripotency in early development.
AB  - The earliest steps of embryonic development involve important changes in
      chromatin and transcription factor networks, which are orchestrated to establish
      pluripotent cells that will form the embryo. DNA methylation, histone
      modifications, the pluripotency regulatory network of transcription factors,
      maternal factors and newly translated proteins all contribute to these
      transitions in dynamic ways. Moreover, these dynamics are linked to the onset of
      zygotic transcription. We will review recent progress in our understanding of
      chromatin state and regulation of gene expression in the context of embryonic
      development in vertebrates, in particular mouse, Xenopus and zebrafish. We
      include work on mouse embryonic stem cells and highlight work that illustrates
      how early embryonic dynamics establish gene regulatory networks and the state of
      pluripotency. 

PMID- 25857443
TI  - Nutritional deficiencies after sleeve gastrectomy: can they be predicted
      preoperatively?
AB  - BACKGROUND: Nutritional deficiencies are common among morbidly obese patients.
      Data are scarce for patients who have undergone laparoscopic sleeve gastrectomy
      (LSG). OBJECTIVES: The aim of the study is to clarify the prevalence of
      deficiencies and to identify risk factors for postoperative deficiencies.
      SETTINGS: Hebrew University, Israel. METHODS: Preoperative and 1-year
      postoperative data were collected. We included anthropometric parameters, obesity
      related co-morbidities, and laboratory findings. RESULTS: There were 192
      candidates. Seventy-seven of them completed follow-ups at 12 months. Before
      surgery, 15% had anemia. Deficiencies of iron, folate, and B12 were 47%, 32%, and
      13%, respectively. Women were more deficient in iron (56% women, 26% men,
      P<.001). Before surgery, low levels of vitamin D and elevated parathyroid hormone
      (PTH) were 99% and 41%, respectively. One year postsurgery, the deficiencies of
      hemoglobin and vitamin B12 worsened (20% and 17%, P<.001, P = .048,
      respectively). One year postsurgery, deficiencies of iron, folate, vitamin D, and
      PTH improved (28%, 21%, 94%, and 10%, respectively). Deficiencies of hemoglobin,
      folate, and B12 before surgery were predictors for deficiencies 1 year after
      surgery (P = .006 OR = .090; P = .012 OR = .069; P = .062 OR = .165,
      respectively). CONCLUSIONS: LSG had a modest effect on nutritional deficiencies
      in our patients at 1-year postsurgery. Focusing on the preoperative nutritional
      status and tailoring a specific supplemental program for each individual should
      prevent postoperative deficiencies.

PMID- 25857444
TI  - Organic neem compounds inhibit soft-rot fungal growth and improve the strength of
      anthracite bricks bound with collagen and lignin for use in iron foundry cupolas.
AB  - AIMS: To examine organic neem compounds for their effective growth inhibition of
      saprotrophic soft-rot fungi on anthracite bricks bound with collagen and lignin
      for use in iron foundry cupolas as an alternative fuel source. METHODS AND
      RESULTS: Azadirachtin, crude neem oil (NO), and clarified neem oil extract (CNO)
      were combined with copper to inhibit the growth of the soft-rot fungus,
      Chaetomium globosum. A synergistic interaction was observed between CNO and a low
      dose of copper on nutrient media (two-factor anova with triplicate replication: P
      < 0.05). Interaction was confirmed on lab-scale collagen-lignin-anthracite
      briquettes by measuring their unconfined compressive (UC) strength. The effective
      collagen strength of the briquettes was enhanced by applying CNO to their surface
      prior to inoculation: the room temperature UC strength of the briquettes was 28
      +/- 4.6% greater when CNO (0.4 mg cm(-2) ) was surface-applied, and was 43 +/-
      3.0% greater when CNO plus copper (0.14 MUg cm(-2) ) were surface-applied.
      CONCLUSION: Surface application of CNO and copper synergistically prevents fungal
      growth on bindered anthracite briquettes and increases their room temperature
      strength. SIGNIFICANCE AND IMPACT OF THE STUDY: This novel organic fungicidal
      treatment may increase the storage and performance of anthracite bricks in iron
      foundries, thereby saving 15-20% of the energy used in conventional coke
      production.

PMID- 25857445
TI  - MicroRNA-29a induces apoptosis via increasing the Bax:Bcl-2 ratio in dermal
      fibroblasts of patients with systemic sclerosis.
AB  - The most prominent feature of systemic sclerosis (SSc) and other diseases
      associated with fibrosis is the prolonged activation of fibroblasts not
      eliminated by apoptosis, hence characterized by accumulation of more extra
      cellular matrix (ECM). We tend to verify if microRNA-29a (miR-29a) as an anti
      fibrotic factor could induce apoptosis in SSc fibroblasts. We did not detect
      apoptosis in SSc fibroblasts. We found that Bcl-2 expression was upregulated in
      SSc fibroblasts and the ratio of Bax:Bcl-2 in these cells was significantly lower
      (p = 0.02) compared to normal fibroblasts. Transfection of both SSc and
      transforming growth factor-beta (TGF-beta) stimulated fibroblasts by miR-29a
      mimic, significantly decreased the expression of two anti-apoptotic members of
      the Bcl-2 family, Bcl-2 (p = 0.0005, p = 0.01) and Bcl-XL (p = 0.0001, p =
      0.006), resulted in enhanced Bax:Bcl-2 ratio and induced a high rate of
      apoptosis. Recently, miR-29 has been introduced as an anti-fibrotic factor with
      potential therapeutic effect on SSc. Until now, it has not been proposed whether
      there is a relationship between miR-29a and apoptosis in SSc. According to our
      results, it seems that miR-29a is a potent inducer of apoptosis in SSc
      fibroblasts and an attenuator of ECM production in these cells. MiR-29a disrupted
      the expression profiling of Bcl-2 family proteins (Bax, Bcl-2 and Bcl-XL) which
      is the central point of dynamic life-death rheostat in many apoptotic pathways.
      Furthermore, dermal fibroblasts from patients with SSc showed elevation in TNF
      alpha mRNA levels, while restoration of miR-29a decreases TNF-alpha production in
      these cells. Although further molecular studies are necessary to investigate the
      underlying apoptotic pathways, the present findings suggest that anti-fibrotic
      and pro-apoptotic properties of miR-29a could provide novel benefits toward the
      development of fibroblast-specific anti-fibrotic therapies.

PMID- 25857446
TI  - Zonisamide reduces nigrostriatal dopaminergic neurodegeneration in a mouse
      genetic model of Parkinson's disease.
AB  - Parkinson's disease (PD) is a chronic neurodegenerative disorder characterized by
      the loss of nigrostriatal dopaminergic neurons and consequent motor dysfunction.
      Zonisamide (1,2-benzisoxazole-3-methanesulfonamide), which was originally
      developed as an antiepileptic drug, has been found to have therapeutic benefits
      for PD. However, the pharmacological mechanisms behind the beneficial actions of
      zonisamide in PD are not fully understood. Here, we investigated the
      neuroprotective effects of zonisamide on nigrostriatal dopaminergic neurons of
      the Engrailed mutant mouse, a genetic model of PD. Chronic administration of
      zonisamide in Engrailed mutant mice was shown to improve the survival of
      nigrostriatal dopaminergic neurons compared with that under saline treatment. In
      addition, dopaminergic terminals in the striatum and the motor function were
      improved in zonisamide-treated Engrailed mutant mice to the levels of those in
      control mice. To clarify the mechanism behind the neuroprotective effects of
      zonisamide, the contents of neurotrophic factors were determined after chronic
      administration of zonisamide. Brain-derived neurotrophic factor content was
      increased in the striatum and ventral midbrain of the zonisamide-treated mice
      compared to saline-treated mice. These findings imply that zonisamide reduces
      nigrostriatal dopaminergic cell death through brain-derived neurotrophic factor
      signaling and may have similar beneficial effects in human parkinsonian patients
      as well.

PMID- 25857447
TI  - Steroid-based treatments for patients with total sudden sensorineural hearing
      loss.
AB  - CONCLUSIONS: In patients with total sudden sensorineural hearing loss (SSNHL),
      oral prednisone (OP) alone or intratympanic dexamethasone (ITD) alone have
      comparable results. The addition of salvage ITD following OP does not seem to add
      over either single modality treatment. OBJECTIVES: To study the effect of steroid
      based treatments in patients with total SSNHL. METHODS: The medical charts of 59
      patients with total loss of hearing, defined as pure tone thresholds in the
      profound range (> 90 dB) with an unobtainable speech reception threshold (SRT)
      that were treated with OP (n = 20), ITD (n = 13), or OP followed by salvage ITD
      (n = 26) were analyzed. Response to treatment was evaluated by means of pure tone
      thresholds, SRT, and speech discrimination score (SDS), immediately after
      treatment and on a follow-up visit. RESULTS: Forty-nine patients (83%) responded
      to treatment, with mean significant improvements of 36, 34, 31, and 25 dB at 500,
      1000, 2000, and 4000 Hz, respectively. The mean improvement in SRT was 33 dB, and
      SDS improved by 32%. There were no differences in improvement in pure tone
      thresholds and SRT among the three treatment groups. The late effect of OP was
      similar to the effect of salvage ITD.

PMID- 25857448
TI  - Are patients with limb and head tremor a clinically distinct subtype of essential
      tremor?
AB  - BACKGROUND: Essential tremor (ET) is the most common tremor disorder in adults.
      In addition to upper limbs, the tremor in ET may also involve head, jaw, voice,
      tongue, and trunk. Though head tremor (HT) is commonly present in patients with
      ET, large comparative studies of ET patients with HT (HT+) and without HT (HT-)
      are few. METHODS: To determine whether ET with HT is a distinct clinical subtype
      by comparing ET patients with and without HT, a chart review of 234 consecutive
      patients with ET attending the neurology clinics of the National Institute of
      Mental Health and Neurosciences, India, was done. A movement disorder specialist
      confirmed the diagnosis of ET in all patients using the National Institutes of
      Health collaborative genetic criteria. RESULTS: HT was present in 44.4% of the
      patients. Comparison between HT+ and HT- showed that the HT+ group patients: (1)
      were older, (2) had later onset of tremor, (3) had unimodal distribution of age
      at onset with a single peak in the fifth decade, (4) had more frequent voice
      tremor, and (5) were more likely to have mild cervical dystonia. HT was part of
      presenting symptoms in nearly two thirds of the ET patients and in the rest it
      was detected during clinical examination. CONCLUSIONS: Several demographic and
      clinical variables suggest that ET patients with HT have a distinct clinical
      phenotype.

PMID- 25857449
TI  - Tobacco smoking and all-cause mortality in a large Australian cohort study:
      findings from a mature epidemic with current low smoking prevalence.
AB  - BACKGROUND: The smoking epidemic in Australia is characterised by historic levels
      of prolonged smoking, heavy smoking, very high levels of long-term cessation, and
      low current smoking prevalence, with 13% of adults reporting that they smoked
      daily in 2013. Large-scale quantitative evidence on the relationship of tobacco
      smoking to mortality in Australia is not available despite the potential to
      provide independent international evidence about the contemporary risks of
      smoking. METHODS: This is a prospective study of 204,953 individuals aged >=45
      years sampled from the general population of New South Wales, Australia, who
      joined the 45 and Up Study from 2006-2009, with linked questionnaire,
      hospitalisation, and mortality data to mid-2012 and with no history of cancer
      (other than melanoma and non-melanoma skin cancer), heart disease, stroke, or
      thrombosis. Hazard ratios (described here as relative risks, RRs) for all-cause
      mortality among current and past smokers compared to never-smokers were
      estimated, adjusting for age, education, income, region of residence, alcohol,
      and body mass index. RESULTS: Overall, 5,593 deaths accrued during follow-up
      (874,120 person-years; mean: 4.26 years); 7.7% of participants were current
      smokers and 34.1% past smokers at baseline. Compared to never-smokers, the
      adjusted RR (95% CI) of mortality was 2.96 (2.69-3.25) in current smokers and was
      similar in men (2.82 (2.49-3.19)) and women (3.08 (2.63-3.60)) and according to
      birth cohort. Mortality RRs increased with increasing smoking intensity, with
      around two- and four-fold increases in mortality in current smokers of <=14 (mean
      10/day) and >=25 cigarettes/day, respectively, compared to never-smokers. Among
      past smokers, mortality diminished gradually with increasing time since cessation
      and did not differ significantly from never-smokers in those quitting prior to
      age 45. Current smokers are estimated to die an average of 10 years earlier than
      non-smokers. CONCLUSIONS: In Australia, up to two-thirds of deaths in current
      smokers can be attributed to smoking. Cessation reduces mortality compared with
      continuing to smoke, with cessation earlier in life resulting in greater
      reductions.

PMID- 25857450
TI  - Effects of MBL2 polymorphisms in patients with diisocyanate-induced occupational
      asthma.
AB  - Diisocyanate (DI) is the most common cause of occupational asthma (OA) in Korea.
      Mannose-binding lectin (MBL) initiates the lectin complement activation pathway
      following oxidative stress and plays an important role in the regulation of
      inflammatory processes. To determine whether there is a genetic association
      between MBL2 polymorphisms and DI-OA, 99 patients with DI-OA, 99 asymptomatic
      exposed controls (AECs) and 144 unexposed normal controls were enrolled in this
      study. Three polymorphisms (-554 G>C, -431A>C and -225 G>C) in the MBL2 promoter
      were genotyped, and serum MBL levels were determined by enzyme-linked
      immunosorbent assay. Functional variabilities in the promoter polymorphisms were
      analyzed by a luciferase reporter assay and electrophoretic mobility shift assay
      (EMSA). A significantly higher frequency of haplotype (ht) 2 [CAG] was noted in
      the DI-OA group compared with the AEC group (P=0.044). The patients with DI-OA
      carrying ht2 [CAG] had significantly lower PC20 methacholine levels (P<0.001)
      than the non-carriers. The serum MBL levels were significantly higher in the DI
      exposed subjects (both the DI-OA patients and AECs) carrying ht1 [GAG] (P=0.028).
      Luciferase activity was significantly enhanced in ht1 [GAG] compared with ht2
      [CAG] in human hepatocarcinoma cells (Hep3B) (P=0.002). The EMSA showed that a 
      554G probe produced a specific shifted band compared with the -554C probe. These
      findings suggest that decreased serum MBL levels due to polymorphisms of the MBL2
      gene may increase susceptibility to the development of DI-OA in DI-exposed
      individuals. 

PMID- 25857451
TI  - Secular changes in intakes of foods among New Zealand adults from 1997 to
      2008/09.
AB  - OBJECTIVE: To examine changes in the food choices of New Zealand (NZ) adults,
      between the 1997 National Nutrition Survey (NNS97) and the 2008/09 NZ Adult
      Nutrition Survey (2008/09 NZANS). DESIGN: The 2008/09 NZANS and the NNS97 were
      cross-sectional surveys of NZ adults (aged 15 years and over). Dietary intake
      data were collected using a computer-based 24 h diet recall. Logistic regression
      models were used to examine changes over time in the percentage reporting each
      food group, with survey year, sex and age group (19-30 years, 31-50 years, 51-70
      years, >=71 years) as the variables. SETTING: NZ households. SUBJECTS: Adults
      aged 19 years and over (NNS97, n 4339; 2008/09 NZANS, n 3995). RESULTS: In the
      2008/09 NZANS compared with NNS97, males and females were less likely to report
      consuming bread, potatoes, beef, vegetables, breakfast cereal, milk, cheese,
      butter, pies, biscuits, cakes and puddings, and sugar/confectionery (all
      P<0.001). In contrast, there was an increase in the percentage reporting rice and
      rice dishes (P<0.001), and among females a reported increase in snacks and snack
      bars (e.g., crisps, extruded snacks, muesli bars; P=0.007) and pasta and pasta
      dishes (P=0.017). Although food choices were associated with sex and age group,
      there were few differential changes between the surveys by sex or age group.
      CONCLUSIONS: For all age groups there was a shift in the percentage who reported
      consuming the traditional NZ foods, namely bread, beef, potatoes and vegetables,
      towards more rice and rice dishes. Declines in the consumption of butter, pies,
      biscuits, cakes and puddings are congruent with current dietary guidelines.

PMID- 25857452
TI  - Bivalirudin in stable angina and acute coronary syndromes.
AB  - A parenteral anticoagulant is indicated in patients with acute coronary
      syndromes. Which anticoagulant should be preferred in each setting is not clearly
      established. Bivalirudin administration was considered in acute coronary
      syndromes after several clinical trials showed decreased bleeding risk with its
      use compared with the association of unfractionated heparin (UFH) with
      glycoprotein IIb/IIIa inhibitors (GPIs). Most recent data demonstrate that the
      bleeding benefit identified in the previous studies was not due to bivalirudin's
      properties but to higher bleeding incidence in the comparator arm due to the
      disproportional use of GPIs with heparin. This paper reviews clinical evidence on
      bivalirudin as anticoagulant in stable angina and acute coronary syndromes. 

PMID- 25857453
TI  - Epigenetic targets and drug discovery Part 2: Histone demethylation and DNA
      methylation.
AB  - Chromatin structure is dynamically modulated by various chromatin modifications,
      such as histone/DNA methylation and demethylation. We have reviewed histone
      methyltransferases and methyllysine binders in terms of small molecule screening
      and drug discovery in the first part of this review series. In this part, we will
      summarize recent progress in chemical probe and drug discovery of histone
      demethylases and DNA methyltransferases. Histone demethylation and DNA
      methylation have attracted a lot of attention regarding their biology and disease
      implications. Correspondingly, many small molecule compounds have been designed
      to modulate the activity of histone demethylases and DNA methyltransferases, and
      some of them have been developed into therapeutic drugs or put into clinical
      trials. 

PMID- 25857455
TI  - Dielectrophoretic isolation of cells using 3D microelectrodes featuring
      castellated blocks.
AB  - We present 3D microelectrodes featuring castellated blocks for
      dielectrophoretically isolating cells. These electrodes provide a more effective
      dielectrophoretic force field than thin-film surface electrodes and yet
      immobilize cells near stagnation points across a parabolic flow profile for
      enhanced cell viability and separation efficiency. Unlike known volumetric
      electrodes with linear profiles, the electrodes with structural variations
      introduced along their depth scale are versatile for constructing monolithic
      structures with readily integrated fluidic paths. This is exemplified here in the
      design of an interdigitated comb array wherein electrodes with castellated
      surfaces serve as building blocks and form digits with an array of fluidic pores.
      Activation of the design with low-voltage oscillations (+/-5 Vp, 400 kHz) is
      found adequate for retaining most viable cells (90.2% +/- 3.5%) while removing
      nonviable cells (88.5% +/- 5%) at an increased throughput (5 * 10(5) cells h(
      1)). The electrodes, despite their intricate profile, are structured into single
      crystal silicon through a self-aligned etching process without a precision layer
      by-layer assembly. 

PMID- 25857454
TI  - The orexin 1 receptor modulates kappa opioid receptor function via a JNK
      dependent mechanism.
AB  - The orexin 1 receptor (OX1R) and the kappa opioid receptor (KOR) are two G
      protein-coupled receptors (GPCRs) previously demonstrated to play important roles
      in modulating the rewarding effects of drugs of abuse such as cocaine. Using
      cells heterologously expressing both receptors, we investigated whether OX1R can
      regulate the function of KOR and vice versa. Activation of OX1R was found to
      attenuate agonist-activated KOR-mediated inhibition of cAMP production. In
      contrast, agonist-activated KOR-mediated beta-arrestin recruitment and p38
      activation were enhanced in the presence of activated OX1R. These effects are
      independent of OX1R internalization but are blocked in the presence of the JNK
      inhibitor SP-600125. OX1R signaling does not affect ligand binding by KOR. Taken
      together, these data suggest that OX1R signaling can modulate KOR function in a
      JNK-dependent manner, promoting preferential signaling of KOR via beta
      arrestin/p38 rather than Galphai. Conversely, Galphaq coupling of OX1R is
      unaffected by activation of KOR, suggesting that this crosstalk is
      unidirectional. Given that KOR Galphai-mediated signaling events and beta
      arrestin-mediated signaling events are thought to promote distinct cellular
      responses and physiological outcomes downstream of KOR activation, this mechanism
      may have important implications on the behavioral effects of KOR activity. 

PMID- 25857456
TI  - A midstream urine collector is not a good alternative to a sterile collection
      method during the diagnosis of urinary tract infection.
AB  - AIM: Guidelines recommend collecting urine with suprapubic aspiration or urethral
      catheterisation in infants with a suspected urinary tract infection (UTI), but
      the invasiveness of these methods continues to drive research on new urine
      collection devices. We studied children with a suspected UTI, who had not been
      toilet trained, to compare a new midstream urine collector and catheterisation.
      METHOD: During this prospective controlled diagnosis study of 94 children, urine
      collection was performed using the midstream collector and then controlled via
      catheterisation when the urine dipstick was positive. RESULTS: When end stream
      samples collected by the midstream collector were compared to catheter samples,
      the results were inconsistent in 23.4% of cases, similar to the inconsistent
      results between first stream samples discarded by the device and the catheter
      samples (21.3%). Interestingly, the overall rate of sample contamination in the
      bag of the midstream collector was lower than that reported in previously
      published studies and there were no false positive bag results. CONCLUSION: The
      midstream collector did not appear to provide additional benefits to classic
      collection bags. A sterile collection method, such as suprapubic aspiration,
      catheterisation or clean catch, is still mandatory for diagnosing urinary tract
      infections in children who are not toilet trained.

PMID- 25857457
TI  - [Unilateral mydriasis in Lyme neuroborreliosis].

PMID- 25857458
TI  - [What may be the contribution of new technologies in the field of genetics of
      ALS?].

PMID- 25857459
TI  - Is de Zurbaran's "Saint Hugo in the refectory" the earliest example of portrayal
      of Parkinson's disease?

PMID- 25857460
TI  - [Physiology and psychiatry: Lhermitte's inaugural lecture in 1923].

PMID- 25857461
TI  - Safety of early initiation of rivaroxaban or dabigatran after thrombolysis in
      acute ischemic stroke.
AB  - The introduction of direct oral anticoagulants (DOA) in the early stage of
      cerebral infarction after thrombolysis may reduce the recurrence rate but raises
      safety concern. We sought to study the feasibility and safety of the introduction
      of rivaroxaban or dabigatran in this context. Thirty-four consecutive patients
      admitted for ischemic stroke related to non-valvular atrial fibrillation in whom
      DOA were given within the first two weeks following intravenous rt-PA were
      studied. A clinical and radiological monitoring protocol was established to
      ensure the safety of the prescription. None of the patients experienced
      symptomatic hemorrhagic transformation or a symptomatic recurrent ischemic event
      after early rivaroxaban or dabigatran introduction. 

PMID- 25857462
TI  - Fibromuscular dysplasia of cervicocephalic arteries: Prevalence of multisite
      involvement and prognosis.
AB  - BACKGROUND: Fibromuscular dysplasia (FMD) is a noninflammatory nonatherosclerotic
      disease of small- to medium-sized arteries. The frequency of multisite
      involvement and its influence on prognosis has not been systematically assessed
      in patients with cervicocephalic FMD, and little is known about their mid-term
      clinical and arterial prognosis. The aim of our study was to assess the
      prevalence of renal involvement and clinical and arterial prognosis in patients
      with cervicocephalic FMD. METHODS: We reviewed clinical and radiological data of
      consecutive patients with a diagnosis of cervicocephalic FMD, admitted to our
      hospital between January 2000 and March 2010. Patients were identified
      retrospectively until December 2008, and prospectively from January 2009. For
      each cervical and intracranial artery, we recorded the presence and type
      (unifocal or multifocal) of FMD. We classified each FMD-related stenosis into
      four categories:<50%, 50-80%,>80% and occlusion. During the first six months of
      2012, patients were scheduled for follow-up visit, including cervicocephalic
      follow-up imaging, and renal artery imaging, if not already available. On follow
      up imaging, FMD-related stenosis was classified according to the same method used
      at baseline. Renal artery FMD was defined as the presence of the typical string
      of beads appearance, or as the presence of a unique stenosis of renal artery.
      Primary endpoints were stroke (ischemic or hemorrhagic), death, and progression
      of FMD lesions, defined by any increase in category of stenosis on follow-up
      imaging. RESULTS: Out of the 36 patients included (32 women), all with carotid
      artery involvement and 17 with associated vertebral artery involvement, 28 (78%)
      had ischemic symptoms and/or cervical artery dissection at the time of the
      diagnosis of FMD. Among the 30 patients who had renal artery imaging, 13 (43%)
      had renal FMD. Patients with renal artery disease did not differ from those
      without renal artery disease. After a median follow-up of 3.5 years, three
      patients had four strokes, one recurrent cervical dissection, one brain
      hemorrhage, and one fatal cardiac arrhythmia. Among the 31 patients who had
      follow-up imaging, two showed progression of cervicocephalic FMD (occlusion of
      carotid artery). Patients with renal involvement showed a non-significant trend
      toward a higher rate of stroke (P=0.17). CONCLUSIONS: In patients with
      cervicocephalic FMD, renal involvement is common. The risk of stroke, death or
      FMD progression was high in our cohort, suggesting that prognosis may not be as
      good as expected. This underlines the need for larger prospective studies to
      define the best treatment options.

PMID- 25857463
TI  - Colorectal Cancer Metastases Settle in the Hepatic Microenvironment Through
      alpha5beta1 Integrin.
AB  - Colorectal cancer (CRC) metastasis dissemination to secondary sites represents
      the critical point for the patient's survival. The microenvironment is crucial to
      cancer progression, influencing tumour cell behaviour by modulating the
      expression and activation of molecules such as integrins, the cell-extracellular
      matrix interacting proteins participating in different steps of the tumour
      metastatic process. In this work, we investigated the role of alpha5beta1
      integrin and how the microenvironment influences this adhesion molecule, in a
      model of colon cancer progression to the liver. The culture medium conditioned by
      the IHH hepatic cell line, and the extracellular matrix (ECM) proteins, modulate
      the activation of alpha5beta1 integrin in the colon cancer cell line HCT-116, and
      drives FAK phosphorylation during the process of cell adhesion to fibronectin,
      one of the main components of liver ECM. In these conditions, alpha5beta1
      modulates the expression/activity of another integrin, alpha2beta1, involved in
      the cell adhesion to collagen I. These results suggest that alpha5beta1 integrin
      holds a leading role in HCT-116 colorectal cancer cells adhesion to the ECM
      through the modulation of the intracellular focal adhesion kinase FAK and the
      alpha2beta1 integrin activity. The driving role of the tumour microenvironment on
      CRC dissemination, here detected, and described, strengthens and adds new value
      to the concept that alpha5beta1 integrin can be an appropriate and relevant
      therapeutic target for the control of CRC metastases.

PMID- 25857464
TI  - Closure of a colon perforation with an autologous fat plug.

PMID- 25857465
TI  - Successful management of traumatic pancreatic transection using ERCP-guided
      pancreatic stenting.

PMID- 25857466
TI  - "Chinese weevils" (Ulomoides dermestoides) found incidentally during colonoscopy.

PMID- 25857467
TI  - Rescue therapy with over-the-scope clip closure for a large postoperative colonic
      leak.

PMID- 25857468
TI  - Benign distal jejunal stricture treated by a partially covered esophageal stent
      with the use of spiral enteroscopy.

PMID- 25857469
TI  - A rare case of extramedullary hematopoiesis in the mediastinum diagnosed by
      endoscopic ultrasound.

PMID- 25857470
TI  - Duodenal perforation from a pen.

PMID- 25857471
TI  - Esophageal microabscesses: an alternative presentation of eosinophilic
      esophagitis.

PMID- 25857472
TI  - Colonoscope incarceration in an inguinal hernia: a complication of colonoscopy.

PMID- 25857473
TI  - Unprecedented case of duodenal papillary disinsertion after endoscopic
      papillectomy for a neuroendocrine tumor.

PMID- 25857474
TI  - A novel approach to esophageal stent removal in the setting of proximal stenosis
      and failure of the primary retrieval mechanism.

PMID- 25857475
TI  - Endoscopic closure of a gastropleural fistula.

PMID- 25857476
TI  - Pyogenic granuloma in the small intestine: a rare cause of obscure
      gastrointestinal bleeding.

PMID- 25857477
TI  - First European human gastric peroral endoscopic myotomy, for treatment of
      refractory gastroparesis.

PMID- 25857478
TI  - Suffering as an independent component of the experience of pain.
AB  - BACKGROUND: Pain has consistently been viewed as containing two dimensions, a
      sensory (intensity) and an emotional (unpleasantness). It has been suggested that
      pain involves higher order cognitive processes that go beyond unpleasantness. We
      therefore aimed at extending the assessment of pain by introducing an additional
      dimension of pain-related suffering and identifying noxious stimulation protocols
      that are most adequate for its psychophysical and psychophysiological
      characterization. METHODS: Twenty-four healthy volunteers received separate
      series of tonic and phasic noxious mechanical stimuli. Visual analogue scales
      were used to rate intensity, unpleasantness and suffering and psychophysiological
      measurements such as heart rate, skin conductance and corrugator electromyography
      were recorded. Acoustically evoked startle responses were measured in part of the
      assessments to obtain additional indicators of pain aversiveness. RESULTS:
      Spearman's correlation coefficients and partial correlations analyses as well as
      principal component analyses confirmed that suffering constitutes an integral
      component of pain processing that is distinct from intensity and unpleasantness.
      Tonic, rather than phasic, stimulation method was more effective in eliciting
      pain and suffering and under this condition startle responses where higher during
      long compared to short stimuli. CONCLUSIONS: These results suggest that in acute
      pain, suffering is a constitutive dimension that might even be more crucial in
      clinical states of pain.

PMID- 25857479
TI  - Korean Red Ginseng Extract Enhances the Anticancer Effects of Imatinib Mesylate
      Through Abrogation p38 and STAT5 Activation in KBM-5 Cells.
AB  - Although imatinib mesylate (IM) in the treatment of chronic myelogenous leukemia
      (CML) remains the best example of successful targeted therapy, majority of
      patients with CML suffer its toxicity profile and develop chemoresistance to
      existing therapeutic agents. Thus, there is a need to develop novel alternative
      therapies for the treatment of CML. Here, we investigated whether Korean red
      ginseng extract (KRGE) could suppress the proliferation and induce
      chemosensitization in human CML cells. Also, we used a human phospho-antibody
      array containing 46 antibodies against signaling molecules to examine a subset of
      phosphorylation events after treatment. Korean red ginseng extract broadly
      suppressed the proliferation of five different cell lines, but KRGE was found to
      be the most potent inducer of apoptosis against KBM-5 cells. It also abrogated
      the expression of Bcl-2 (B-cell lymphoma 2), Bcl-xL (B-cell lymphoma-extra
      large), survivin, inhibitors of apoptosis protein 1/2, COX-2 (Cyclooxygenase-2),
      cyclin D1, matrix metalloproteinase-9, and VEGF (Vascular endothelial growth
      factor), as well as upregulated the expression of pro-apoptotic gene products.
      Interestingly, KRGE also enhanced the cytotoxic and apoptotic effect of IM in KBM
      5 cells. The combination treatment of KRGE and IM caused pronounced suppression
      of p38 and signal transducer and activator of transcription 5 phosphorylation and
      induced phosphorylation of p53 compared with the individual treatment. Our
      results demonstrate that KRGE can enhance the anticancer activity of IM and may
      have a substantial potential in the treatment of CML.

PMID- 25857481
TI  - Planning an MR suite: What can be done to enhance safety?
AB  - Magnetic resonance imaging (MRI), frequently touted as the "the safe modality,"
      suffers from significant, and growing, numbers of preventable adverse events.
      Improvements in MR safety can result from enhancements to expected operational
      elements: training, screening, and patient-management protocols. Less frequently
      considered is the safety benefits that may be realized through smart design of MR
      facilities. Through conscientious and thorough prospective site planning
      involving MR staff and radiologists in the design process for MR physical
      facilities, MR providers can have a positive impact on improving safety as well
      as efficiency for the benefit of their patients, for ancillary healthcare
      workers, and for themselves.

PMID- 25857480
TI  - Chloride channels mediate sodium sulphide-induced relaxation in rat uteri.
AB  - BACKGROUND AND PURPOSE: Hydrogen sulphide reduces uterine contractility and is of
      potential interest as a treatment for uterine disorders. The aim of this study
      was to explore the mechanism of sodium sulphide (Na2 S)-induced relaxation of rat
      uterus, investigate the importance of redox effects and ion channel-mediated
      mechanisms, and any interactions between these two mechanisms. EXPERIMENTAL
      APPROACH: Organ bath studies were employed to assess the pharmacological effects
      of Na2 S in uterine strips by exposing them to Na2 S with or without Cl(-)
      channel blockers (DIDS, NFA, IAA-94, T16Ainh-A01, TA), raised KCl (15 and 75 mM),
      K(+) channel inhibitors (glibenclamide, TEA, 4-AP), L-type Ca(2+) channel
      activator (S-Bay K 8644), propranolol and methylene blue. The activities of
      antioxidant enzymes were measured in homogenates of treated uteri. The expression
      of bestrophin channel 1 (BEST-1) was determined by Western blotting and RT-PCR.
      KEY RESULTS: Na2 S caused concentration-dependent reversible relaxation of
      spontaneously active and calcium-treated uteri, affecting both amplitude and
      frequency of contractions. Uteri exposed to 75 mM KCl were less sensitive to Na2
      S compared with uteri in 15 mM KCl. Na2 S-induced relaxations were abolished by
      DIDS, but unaffected by other modulators or by the absence of extracellular HCO3
      (-) , suggesting the involvement of chloride ion channels. Na2 S in combination
      with different modulators provoked specific changes in the anti-oxidant profiles
      of uteri. The expression of BEST-1, both mRNA and protein, was demonstrated in
      rat uteri. CONCLUSIONS AND IMPLICATIONS: The relaxant effects of Na2 S in rat
      uteri are mediated mainly via a DIDS-sensitive Cl(-) -pathway. Components of the
      relaxation are redox- and Ca(2+) -dependent.

PMID- 25857482
TI  - Transgenic and cloned animals in the food chain--are we prepared to tackle it?
AB  - Transgenic and cloned animal production for various purposes has been increasing
      rapidly in recent times. While the actual impact of these animals in the food
      chain is unknown, the significance of tracking and monitoring measures to curb
      accidental and or deliberate release has been discussed. Religious perspectives
      from different faiths and traditions have been presented. Although the concept of
      substantial equivalence satisfies the technical and nutritional requirements of
      these products when assessed against comparators, public opinion and religious
      concerns should also be considered by the regulators while developing policy
      regulations. In conclusion, measures to prevent real or perceived risks of
      transgenic and cloned animals in food production require global coordinated
      action. It is worthwhile to consider establishing effective tracking systems and
      analytical procedures as this will be a valuable tool if a global consensus is
      not reached on policy regulation.

PMID- 25857483
TI  - Biodistribution of the multidentate hydroxypyridinonate ligand [(14) C]-3,4,3
      LI(1,2-HOPO), a potent actinide decorporation agent.
AB  - The pharmacokinetics and biodistribution of the (14) C-labeled actinide
      decorporation agent 3,4,3-LI(1,2-HOPO) were investigated in young adult Swiss
      Webster mice and Sprague Dawley rats, after intravenous, intraperitoneal, and
      oral dose administration. In all routes investigated, the radiolabeled compound
      was rapidly distributed to various tissues and organs of the body. In mice, the
      24 h fecal elimination profiles suggested that the biliary route is the
      predominant route of elimination. In contrast, lower fecal excretion levels were
      observed in rats. Tissue uptake and retention of the compound did not differ
      significantly between sexes although some differences were observed in the
      excretion patterns over time. The male mice eliminated a greater percentage of
      (14) C through the renal pathway than the female mice after receiving an
      intravenous or intraperitoneal dose, while the opposite trend was seen in rats
      that received an intravenous dose. Metabolite profiling performed on selected rat
      samples demonstrated that a putative major metabolite of [(14) C]-3,4,3-LI(1,2
      HOPO) is formed, accounting for approximately 10% of an administered oral dose.
      Finally, to improve its oral bioavailability, 3,4,3-LI(1,2-HOPO) was coformulated
      with a proprietary permeability enhancer, leading to a notable increase in oral
      bioavailability of the compound.

PMID- 25857486
TI  - Patients' decision-making experiences in the acute healthcare setting--a case
      study.
AB  - BACKGROUND: The transition from being an ordinary citizen to a hospitalised
      patient can be a daunting experience particularly for the uninitiated and
      inexperienced. Patients are likely to have questions such as 'where do I go?',
      'what should I do?', 'when?' and 'who should I ask?' The process for making
      practical moment-to-moment decisions is often complex and fraught with
      difficulties. Identifying critical points in the hospitalisation experience may
      provide insights into the quality of hospital management systems and professional
      practices from a patient perspective. OBJECTIVE: This study aimed to identify
      institutional practices and structures in the context of acute healthcare
      settings which impact on patient moment-to-moment decision-making experiences.
      METHOD: A case study approach was used as the exploratory methodology, and
      interviews were conducted with three former adult inpatients. In order to gain an
      understanding of each participant's experiences, data collecting strategies used
      in this research were a semistructured interview and document analysis of
      information documents, such as hospital supplied pamphlets, provided to the
      researcher by the participants. RESULTS: The study identified five major themes.
      Identified as being critical to the participants were information sharing by
      healthcare professionals, professional advice and professional role
      identification. Less so were environment and everyday life. Associated with these
      themes were the participant's common experience of being confined in unfamiliar
      surroundings, adjusting to institutional routines and of being heavily dependent
      on others. CONCLUSION: Findings indicate that patient moment-to-moment decision
      making may be informed and enhanced in several areas: relevant and timely
      information sharing, varying the dress code between the different professions,
      reducing conflicting professional advice, clear signage around the hospital, and
      flexible visiting hours, telephones and clocks in patient rooms.

PMID- 25857484
TI  - Psychometric Analysis of Behavioral Pain Scale Brazilian Version in Sedated and
      Mechanically Ventilated Adult Patients: A Preliminary Study.
AB  - BACKGROUND AND PURPOSE: Pain assessment in Intensive Care Units (ICU) can be
      performed based on validated instruments as the Behavioral Pain Scale (BPS).
      Despite the existence of this clinical score, there is no Brazilian version of it
      to assess critically ill patients. This study aimed to translate the BPS into
      Brazilian Portuguese, verify its psychometric properties (reliability, validity,
      and responsiveness) and the correlation between pain measured and heart rate
      (HR), blood pressure (BP), Ramsay, and RASS scores. METHODS: Pain intensity by
      using Brazilian BPS version, HR, and BP were observed by 2 investigators during 3
      different moments: at rest; during eye cleaning (EC); and tracheal suctioning
      (TS) in 15 adult subjects sedated and mechanically ventilated. Sedation level,
      severity of disease, and use of sedatives and analgesic drugs were also recorded.
      RESULTS: There was a high responsiveness coefficient (coefficient = 1.72) and
      pain was significantly higher during tracheal suctioning (P <= 0.003) and eye
      cleaning (P <= 0.04) than at rest. It was evidenced a low reliability and no
      significant correlation between translated BPS scores and physiological
      parameters during tracheal suctioning, sedation scales, flow of the sedatives
      drugs, or with the general health status (P > 0.07). CONCLUSION: Brazilian BPS
      has high responsiveness and capacity to detect pain intensity in different
      situations in the ICU routine. This preliminary study proved the feasibility and
      importance of valid this scale in Brazil in order to improve critically ill
      patients care.

PMID- 25857487
TI  - Bone Microstructure of the Stereospondyl Lydekkerina Huxleyi Reveals Adaptive
      Strategies to the Harsh Post Permian-Extinction Environment.
AB  - The small-bodied stereospondyl Lydekkerina huxleyi, dominated the amphibian fauna
      of the South African Lower Triassic. Even though the anatomy of this amphibian
      has been well described, its growth strategies and lifestyle habits have remained
      controversial. Previous studies attributed the relative uniformity in skull sizes
      to a predominance of subadult and adult specimens recovered in the fossil record.
      Anatomical and taphonomic data suggested that the relatively small body-size of
      this genus, as compared to its Permo-Triassic relatives, could be linked to a
      shortened, rapid developmental period as an adaptation to maintain successful
      breeding populations under harsh environmental conditions. Moreover,
      Lydekkerina's habitat has been hypothesized to be either aquatic or mainly
      terrestrial. The current study, utilizes bone microstructure to reassess previous
      hypotheses pertaining to the biology and ecology of Lydekkerina. Various skeletal
      elements of different-sized specimens are analyzed to understand its growth
      dynamics, intraskeletal variability, and lifestyle adaptations. Bone histology
      revealed that our sample comprises individuals at different ontogenetic stages
      i.e., juveniles to mature individuals. Our results show that these amphibians,
      despite exhibiting plasticity in growth, experienced an overall faster growth
      during early ontogeny (thereby attaining sexual maturity sooner), as compared to
      most other temnospondyls. The microanatomy of the long bones with their thick
      bone walls and distinctive medullary cavity suggests that Lydekkerina may have
      been amphibious with a tendency to be more terrestrial. Our study concludes that
      Lydekkerina employed a peculiar growth strategy and lifestyle adaptations, which
      enabled it to endure the harsh, dry conditions of the Early Triassic.

PMID- 25857488
TI  - World Leprosy Day 2015: renewing commitment for a leprosy free world!

PMID- 25857489
TI  - Lung cancer: prevalent trends & emerging concepts.

PMID- 25857490
TI  - Proteomics of multidrug resistant Mycobacterium tuberculosis clinical isolates: a
      peep show on mechanism of drug resistance & perhaps more.

PMID- 25857491
TI  - Health & nutritional status of HIV infected children.

PMID- 25857493
TI  - Comparative proteomic analysis of sequential isolates of Mycobacterium
      tuberculosis from a patient with pulmonary tuberculosis turning from drug
      sensitive to multidrug resistant.
AB  - BACKGROUND & OBJECTIVES: Tuberculosis is a major health problem in India, and the
      emergence of multidrug resistant (MDR) and extensively drug resistant (XDR)
      strains of Mycobacterium tuberculosis (Mtb) has further complicated the
      situation. Though several studies characterizing drug sensitive and drug
      resistant strains are available in literature, almost all studies are done on
      unrelated strains. Therefore, the objective of this study was to compare the
      proteomic data of four sequential isolates of Mtb from a single patient who
      developed MDR-TB during the course of anti-tuberculosis therapy (ATT). METHODS:
      In this study, using two-dimensional (2D) gel electrophoresis and MALDI-TOF mass
      spectrometry, we compared and analyzed the cell lysate proteins of Mtb sequential
      clinical isolates from a patient undergoing anti-TB treatment. The mRNA
      expression levels of selected identified proteins were determined by quantitative
      real-time polymerase chain reaction (qRT-PCR). RESULTS: The genotypes of all four
      isolates remained homologous, indicating no re-infection. The initial isolate
      (before treatment) was sensitive to all first-line drugs, but the consecutive
      isolates were found to be resistant to isoniazid (INH) and rifampicin (RIF) and
      developed mutations in the katG, inhA and rpoB. the intensities of 27 protein
      spots were found to be consistently overexpressed in INH and RIF resistant
      isolates. The most prominent and overexpressed proteins found during the
      development of drug resistance were GarA (Rv1827), wag31 (Rv2145c), Rv1437 and
      Rv2970c. INTERPRETATION & CONCLUSIONS: This preliminary proteomic study provides
      an insight about the proteins that are upregulated during drug resistance
      development. These upregulated proteins, identified here, could prove useful as
      immunodiagnostic and possibly drug resistant markers in future. However, more
      studies are required to confirm these findings.

PMID- 25857492
TI  - Mitochondrial disorders: challenges in diagnosis & treatment.
AB  - Mitochondrial dysfunctions are known to be responsible for a number of
      heterogenous clinical presentations with multi-systemic involvement. Impaired
      oxidative phosphorylation leading to a decrease in cellular energy (ATP)
      production is the most important cause underlying these disorders. Despite
      significant progress made in the field of mitochondrial medicine during the last
      two decades, the molecular mechanisms underlying these disorders are not fully
      understood. Since the identification of first mitochondrial DNA (mtDNA) mutation
      in 1988, there has been an exponential rise in the identification of mtDNA and
      nuclear DNA mutations that are responsible for mitochondrial dysfunction and
      disease. Genetic complexity together with ever widening clinical spectrum
      associated with mitochondrial dysfunction poses a major challenge in diagnosis
      and treatment. Effective therapy has remained elusive till date and is mostly
      efficient in relieving symptoms. In this review, we discuss the important
      clinical and genetic features of mitochondrials disorders with special emphasis
      on diagnosis and treatment. 

PMID- 25857494
TI  - Health & nutritional status of HIV infected children in Hyderabad, India.
AB  - BACKGROUND & OBJECTIVES: Information on nutritional status of HIV infected
      children from India is lacking and is required before taking up nutritional
      supplementation trials. Thus, the aim of the present study was to assess the
      growth and morbidity status of HIV infected children over a period of one year in
      a city in southern India. METHODS: This was an observational study carried out
      between July 2009 and February 2011, at two orphanages in Hyderabad, India.
      Seventy seven HIV-positive children aged between 1 and half and 15 years, both on
      and not on antiretroviral therapy (ART) were included. Nutritional status was
      assessed longitudinally for one year by weight gain, linear growth and body
      composition. Serum samples were analyzed for haemoglobin, micronutrients, CD4 and
      CD8 counts. Dietary intakes were assessed by institutional diet survey and
      morbidity data were recorded every day for 12 months. RESULTS: Mean energy
      intakes were less than recommended dietary allowance (RDA) in all age groups.
      Iron and folate intakes were less than 50 per cent of RDA; 46 (59.7%) children
      were stunted, 36 (46.8%) were underweight and 15 (19.5%) had low BMI for age.
      Anaemia was observed in 35 (45.5%) children. Micronutrient deficiencies such as
      vitamin D (40/77; 51.9%), vitamin A (11/77; 14.3%), folate (37/77; 48.1%), iron
      (38/77; 49.3%) were widely prevalent. HIV viral load was higher in children not
      on ART and those with morbidity. Respiratory (36.6%) and dermatological illnesses
      (18.8%) were the commonest presentations. INTERPRETATION & CONCLUSIONS: Acute,
      chronic malnutrition and micronutrient deficiencies were common in HIV infected
      children, especially in those not on ART and having morbidity. With severe
      malnutrition being an alarming consequence of HIV, prophylactic nutritive care
      should be considered for integration into HIV care strategies besides initiation
      of ART to improve the nutritional status and quality of life of these children.

PMID- 25857495
TI  - Application of IS1311 locus 2 PCR-REA assay for the specific detection of 'Bison
      type' Mycobacterium avium subspecies paratuberculosis isolates of Indian origin.
AB  - BACKGROUND & OBJECTIVES: Of the three major genotypes of Mycobacterium avium
      subspecies paratuberculosis (MAP), 'Bison type' is most prevalent genotype in the
      domestic livestock species of the country, and has also been recovered from
      patients suffering from Crohn's disease. Recently, a new assay based on IS1311
      locus 2 PCR- restriction endonuclease analysis (REA) was designed to distinguish
      between 'Indian Bison type' and non-Indian genotypes. The present study
      investigated discriminatory potential of this new assay while screening of a
      panel of MAP isolates of diverse genotypes and from different geographical
      regions. METHODS: A total of 53 mycobacterial isolates (41 MAP and 12
      mycobacterium other than MAP), three MAP genomic DNA and 36 MAP positive faecal
      DNA samples from different livestock species (cattle, buffaloes, goat, sheep and
      bison) and geographical regions (India, Canada, USA, Spain and Portugal) were
      included in the study. The extracted DNA samples (n=92) were analyzed for the
      presence of MAP specific sequences (IS900, ISMav 2 and HspX) using PCR. DNA
      samples were further subjected to genotype differentiation using IS1311 PCR-REA
      and IS1311 L2 PCR-REA methods. RESULTS: All the DNA samples (except DNA from non
      MAP mycobacterial isolates) were positive for all the three MAP specific
      sequences based PCRs. IS1311 PCR-REA showed that MAP DNA samples of Indian origin
      belonged to 'Bison type'. Whereas, of the total 19 non-Indian MAP DNA samples, 2,
      15 and 2 were genotyped as 'Bison type', 'Cattle type' and 'Sheep type',
      respectively. IS1311 L2 PCR-REA method showed different restriction profiles of
      'Bison type' genotype as compared to non-Indian DNA samples. INTERPRETATION &
      CONCLUSIONS: IS1311 L2 PCR-REA method successfully discriminated 'Indian Bison
      type' from other non-Indian genotypes and showed potential to be future
      epidemiological tool and for genotyping of MAP isolates.

PMID- 25857496
TI  - Serum lipoprotein ratios as markers of insulin resistance: a study among non
      diabetic acute coronary syndrome patients with impaired fasting glucose.
AB  - BACKGROUND & OBJECTIVES: Recent data suggest that insulin resistance can predict
      cardiovascular disease independently of the other risk factors, such as
      hypertension, visceral obesity or dyslipidaemia. However, the majority of
      available methods to evaluate insulin resistance are complicated to operate,
      expensive, and time consuming. This study was undertaken to assess whether serum
      lipoprotein ratios could predict insulin resistance in non-diabetic acute
      coronary syndrome (ACS) patients. METHODS: Ninety non-diabetic patients with
      impaired fasting glucose admitted with a diagnosis of ACS were included in the
      study. At the time of admission fasting glucose and insulin concentrations were
      measured. The homeostatic model assessment-insulin resistance (HOMA-IR) was used
      for insulin resistance. The fasting serum total cholesterol (TC), triglycerides
      (TG) and high density lipoprotein cholesterol (HDL-C) levels were checked, and
      then TC/HDL-C and TG/HDL-C ratios were calculated. The areas under the curves
      (AUC) of the receiver operating characteristic (ROC) curves were used to compare
      the power of these serum lipoprotein ratios as markers. RESULTS: Lipoprotein
      ratios were significantly higher in patients with HOMA-IR index > 2.5 as compared
      to patients with index <2.5 (P < 0.05). Both TG/HDL-C and TC/HDL-C ratios were
      significantly correlated with HOMA-IR (P<0.05). The area under the ROC curve of
      the TG/HDL-C and TC/HDL-C ratio for predicting insulin resistance was 0.80 (95%
      CI, 0.67 to 0.93), 0.78 (95% CI, 0.65 to 0.91), respectively. INTERPRETATION &
      CONCLUSIONS: The findings of this study demonstrate that serum lipoprotein ratios
      can provide a simple means of identifying insulin resistance and can be used as
      markers of insulin resistance and cardiovascular diseases risk in adult non
      diabetic patients.

PMID- 25857497
TI  - Use of plasma triglyceride/high-density lipoprotein cholesterol ratio to identify
      increased cardio-metabolic risk in young, healthy South Asians.
AB  - BACKGROUND & OBJECTIVES: Prevalence of insulin resistance and associated
      dyslipidaemia [high triglyceride (TG) and low high-density lipoprotein
      cholesterol (HDL-C) concentrations] are increased in South Asian individuals;
      likely contributing to their increased risk of type-2 diabetes and cardiovascular
      disease. The plasma concentration ratio of TG/HDL-C has been proposed as a simple
      way to identify apparently healthy individuals at high cardio-metabolic risk.
      This study was carried out to compare the cardio-metabolic risk profiles of high
      risk South Asian individuals identified by an elevated TG/HDL-C ratio versus
      those with a diagnosis of the metabolic syndrome. METHODS: Body mass index, waist
      circumference, blood pressure, and fasting plasma glucose, insulin, TG, and HDL-C
      concentrations were determined in apparently healthy men (n=498) and women
      (n=526). The cardio-metabolic risk profile of "high risk" individuals identified
      by TG/HDL-C ratios in men (>= 3.5) and women (>=2.5) was compared to those
      identified by a diagnosis of the metabolic syndrome. RESULTS: More concentrations
      of all cardio-metabolic risk factors were significantly higher in "high risk"
      groups, identified by either the TG/HDL-C ratio or a diagnosis of the metabolic
      syndrome. TG, HDL-C, and insulin concentrations were not significantly different
      in "high risk" groups identified by either criterion, whereas plasma glucose and
      blood pressure were higher in those with the metabolic syndrome. INTERPRETATION &
      CONCLUSIONS: Apparently healthy South Asian individuals at high cardio-metabolic
      risk can be identified using either the TG/HDL-C ratio or the metabolic syndrome
      criteria. The TG/HDL-C ratio may be used as a simple marker to identify such
      individuals.

PMID- 25857498
TI  - Quantitation of ethyl glucuronide in serum & urine by gas chromatography - mass
      spectrometry.
AB  - BACKGROUND & OBJECTIVES: Alcohol misuse has now become a serious public health
      problem and early intervention is important in minimizing the harm. Biochemical
      markers of recent and high levels of alcohol consumption can play an important
      role in providing feedback regarding the health consequences of alcohol misuse.
      Existing markers are not sensitive to recent consumption and in detecting early
      relapse. Ethyl glucuronide (EtG), a phase-II metabolite of ethanol is a promising
      marker of recent alcohol use and can be detected in body fluids. In this study an
      analytical technique for quantitation of EtG in body fluids using solid-phase
      extraction (SPE) and gas chromatography (GC) with mass spectrometric detection
      (MS) was developed and validated. METHODS: De-proteinization of serum and urine
      samples was done with perchloric acid and hydrochloric acid, respectively. Serum
      samples were passed through phospholipids removal cartridges for further clean
      up. EtG was isolated using amino propyl solid phase extraction columns.
      Chromatographic separation was achieved by gas chromatography with mass
      spectrometry. RESULTS: Limit of detection and limit of quantitation were 50 and
      150 ng/ml for urine and 80 and 210 ng/ml for serum, respectively. Signal to noise
      ratio was 3:1, mean absolute recovery was 80-85 per cent. Significant correlation
      was obtained between breath alcohol and serum EtG levels (r=0.853) and urine EtG
      and time since last abuse (r = -0.903) in clinical samples. INTERPRETATION &
      CONCLUSIONS: In the absence of other standardized techniques to quantitate EtG in
      biological samples, this gc - ms method was found to have high throughput and was
      sensitive and specific.

PMID- 25857499
TI  - Enhanced resistance to fluoroquinolones in laboratory-grown mutants & clinical
      isolates of Shigella due to synergism between efflux pump expression & mutations
      in quinolone resistance determining region.
AB  - BACKGROUND & OBJECTIVES: There is a worldwide emergence of fluoroquinolone
      resistance in Shigella species. To understand the molecular mechanisms associated
      with fluoroquinolone resistance, naturally occurring fluoroquinolone-resistant
      strains and laboratory-induced spontaneous mutants of Shigella spp. were used and
      the relative contributions of acrAB-tolC efflux pumps, gyrase and topoisomerase
      target gene mutations towards fluoroquinolone resistance were determined.
      METHODS: Eight Shigella flexneri and six S. dysenteriae clinical isolates were
      studied. Three consecutive mutants resistant to ciprofloxacin for S. flexneri
      SFM1 (>= 0.25 ug/ml), SFM2 (>= 4 ug/ml) and SFM3 (>= 32 ug/ml) were selected in
      15 steps from susceptible isolates by serial exposure to increasing
      concentrations of nalidixic acid and ciprofloxacin. Similarly, two mutants for S.
      dysenteriae SDM1 (>= 0.25 ug/ml) and SDM2 (>= 4 ug/ml) were selected in eight
      steps. After PCR amplification sequence analyses of gyrase and topoisomerase
      target genes were performed. Expression of efflux genes acrA, acrB, acrR and tolC
      was measured using real-time PCR. RESULTS: Mutations were observed in gyrA Ser
      [83]->Leu, Asp [87]->Asn/Gly, Val [196]->Ala and in parC Phe [93]->Val, Ser [80]
      >Ile, Asp [101]->Glu and Asp [110]->Glu. Overall, acrA and acrB overexpression
      was associated with fluoroquinolone resistance ( p0 <0.05); while tolC and acrR
      expression levels did not. INTERPRETATION & CONCLUSIONS: Fluoroquinolone
      resistance in Shigella spp. is the end product of either a single or a
      combination of mutations in QRDRs and/ or efflux activity. Novel polymorphisms
      were observed at Val [196]->Ala in gyrA in clinical isolates and Phe [93]->Val,
      Asp [101]->Glu, Asp [110]->Glu and in parC in majority of laboratory-grown
      mutants.

PMID- 25857500
TI  - Sudarshan Kriya yoga improves quality of life in healthy people living with HIV
      (PLHIV): results from an open label randomized clinical trial.
AB  - BACKGROUND & OBJECTIVES: Improving quality of life (QOL) of healthy people living
      with HIV (PLHIV) is critical needing home-based, long-term strategy. Sudarshan
      Kriya yoga (SKY) intervention is acknowledged for its positive impact on health.
      It is hypothesised that SKY would improve PLHIV's QOL, justifying an evaluation.
      METHODS: In this open label randomized controlled pilot trial, 61 adult PLHIV
      with CD4 count more than 400 cells/ul and Karnofsky scale score above 70 were
      enrolled. Those with cardiac disease, jaundice, tuberculosis, or on
      antiretroviral therapy/yoga intervention were excluded. All were given standard
      care, randomized to SKY intervention (31: I-SKY) and only standard of care in
      control (30: O-SOC) arms. The I-SKY participants were trained for six days to
      prepare for daily practice of SKY at home for 30 min. A validated 31-item WHOQOL
      HIVBREF questionnaire was used to document effect in both arms from baseline to
      three visits at 4 wk interval. RESULTS: Baseline QOL scores, hypertension and CD4
      count were similar in both arms. An overall 6 per cent improvement of QOL scores
      was observed in I-SKY group as compared to O-SOC group, after controlling for
      baseline variables like age, gender, education and occupation ( p =0.016); 12 per
      cent for physical ( p =0.004), 11 per cent psychological (p =0.023) and 9 per
      cent level of independence (p =0.001) domains. Improvement in I-SKY observed at
      post-training and in the SKY adherence group showed increase in these two
      domains. CONCLUSIONS: A significant improvement in QOL scores was observed for
      the three health related QOL domains in SKY intervention arm. This low cost
      strategy improved physical and psychological state of PLHIV calling for upscaling
      with effective monitoring for sustainability of quality of life.

PMID- 25857503
TI  - Unmet need for contraception among married women in an urban area of Puducherry,
      India.
AB  - BACKGROUND & OBJECTIVES: Unmet need for contraception remains a national problem.
      The study was conducted in an urban area of Puducherry, India, among the eligible
      couples to assess the unmet need for contraception and to determine the awareness
      and pattern of use of contraceptives along with the socio-demographic factors
      associated with the unmet needs for contraception. METHODS: This cross-sectional
      study included eligible couples with married women in age group of 15-45 yr as
      the study population (n=267). Probability proportional to size sampling followed
      by systematic random sampling was used. A pre-tested questionnaire was
      administered to collect data from the respondents. Double data entry and
      validation of data was done. RESULTS: Unmet need for contraception was 27.3 per
      cent (95% CI: 22.3-33); unmet need for spacing and limiting was 4.9 and 22.5 per
      cent, respectively. Among those with unmet need (n=73), 50 per cent reported
      client related factors (lack of knowledge, shyness, etc.); and 37 per cent
      reported contraception related factors (availability, accessibility,
      affordability, side effects) as a cause for unmet need. INTERPRETATION &
      CONCLUSIONS: Our study showed a high unmet need for contraception in the study
      area indicating towards a necessity to address user perspective to meet the
      contraception needs.

PMID- 25857501
TI  - Efficacy & safety evaluation of Ayurvedic treatment (Ashwagandha powder & Sidh
      Makardhwaj) in rheumatoid arthritis patients: a pilot prospective study.
AB  - BACKGROUND & OBJECTIVES: In the traditional system of medicine in India
      Ashwagandha powder and Sidh Makardhwaj have been used for the treatment of
      rheumatoid arthritis. However, safety and efficacy of this treatment have not
      been evaluated. Therefore, the present study was carried out to evaluate the
      efficacy and safety of Ayurvedic treatment (Ashwagandha powder and Sidh
      Makardhwaj) in patients with rheumatoid arthritis. METHODS: One hundred and
      twenty five patients with joint pain were screened at an Ayurvedic hospital in
      New Delhi, India. Eighty six patients satisfied inclusion criteria and were
      included in the study. Detailed medical history and physical examination were
      recorded. Patients took 5g of Ashwagandha powder twice a day for three weeks with
      lukewarm water or milk. Sidh Makardhwaj (100 mg) with honey was administered
      daily for the next four weeks. The follow up of patients was carried out every
      two weeks. The primary efficacy end point was based on American College of
      Rheumatology (ACR) 20 response. Secondary end points were ACR50, ACR70 responses,
      change from baseline in disease activity score (DAS) 28 score and ACR parameters.
      Safety assessments were hepatic function [alanine aminotransferase (ALT),
      aspartate aminotransferase (AST), alkaline phosphatase (ALP), bilirubin and beta2
      microglobulin], renal function (urea and creatinine and NGAL) tests and urine
      mercury level. RESULTS: The study was completed by 90.7 per cent (78/86)
      patients. Patients with moderate and high disease activity were 57.7 per cent
      (45/78) and 42.3 per cent (33/78), respectively. All patients were tested
      positive for rheumatoid factor and increased ESR level. Ashwagandha and Sidh
      Makardhwaj treatment decreased RA factor. A significant change in post-treatment
      scores of tender joint counts, swollen joint counts, physician global assessment
      score, patient global assessment score, pain assessment score, patient self
      assessed disability index score and ESR level were observed as compared to
      baseline scores. ACR20 response was observed in 56.4 per cent (44/78) patients
      (American College of Rheumatology criteria) and moderate response in 39.74 per
      cent (31/78) patients [European League Against Rheumatism (EULAR) criteria].
      Ayurvedic treatment for seven weeks in rheumatoid arthritis patients showed
      normal kidney and liver function tests. However, increased urinary mercury levels
      were was observed after treatment. INTERPRETATION & CONCLUSIONS: The findings of
      the present study suggest that this Ayurvedic treatment (Ashwagandha powder and
      Sidh Makardhwaj) has a potential to be used for the treatment of rheumatoid
      arthritis. However, due to small sample size, short duration, non randomization
      and lack of a control group as study limitations, further studies need to be done
      to confirm these findings.

PMID- 25857502
TI  - Lipoprotein associated phospholipase A2 activity & its correlation with oxidized
      LDL & glycaemic status in early stages of type-2 diabetes mellitus.
AB  - BACKGROUND & OBJECTIVES: Lipoprotein associated phospholipase A 2 (Lp-PLA 2 ) is
      an important risk predictor of coronary artery disease (CAD). This study was
      aimed to evaluate Lp-PLA 2 activity and oxidized low density lipoprotein (oxLDL)
      in newly diagnosed patients of type 2 diabetes mellitus and to determine the
      correlation of Lp-PLA 2 activity with oxLDL and plasma glucose levels. METHODS:
      Blood samples were collected in patients with newly diagnosed type 2 diabetes
      (n=40) before any treatment was started and healthy controls (n=40). These were
      processed for estimating plasma glucose: fasting and post prandial, ox LDL, and
      Lp-PLA2 activity. The parameters in the two groups were compared. Correlation
      between different parameters was calculated by Pearson correlation analysis in
      both groups. RESULTS: Lp-PLA 2 activity (24.48 +/- 4.91 vs 18.63 +/- 5.29
      nmol/min/ml, P<0.001) and oxLDL levels (52.46 +/- 40.19 vs 33.26 +/- 12.54
      MUmol/l, P<0.01) were significantly higher in patients as compared to those in
      controls. Lp-PLA 2 activity correlated positively with oxLDL in both controls
      (r=0.414, P<0.01), as well in patients (r=0.542, P<0.01). A positive correlation
      between Lp-PLA 2 activity and fasting plasma glucose levels was observed only in
      patients (r=0.348, P<0.05). INTERPRETATION & CONCLUSIONS: Result of this study
      implies that higher risk of CAD in patients with diabetes may be due to increase
      in Lp-PLA 2 activity during the early course of the disease. A positive
      correlation between enzyme activity and fasting plasma glucose indicates an
      association between hyperglycaemia and increased activity of Lp-PLA2. This may
      explain a higher occurrence of CAD in patients with diabetes. A positive
      correlation between oxLDL and Lp-PLA2 activity suggests that Lp-PLA2 activity may
      be affected by oxLDL also.

PMID- 25857504
TI  - Unexpected diagnostic findings in some HIV positive individuals in Bangladesh.

PMID- 25857505
TI  - Knowledge, attitude & factors affecting potential use of emergency contraception
      in college students in Puducherry, south India.

PMID- 25857506
TI  - Antibody response to hepatitis B vaccination in isolated anti-HBc positive
      subjects.

PMID- 25857507
TI  - Establishing association.

PMID- 25857508
TI  - Left hepatic lobe herniation through an incisional anterior abdominal wall
      hernia.

PMID- 25857509
TI  - Infectious purpura fulminans.

PMID- 25857510
TI  - Lichenoid skin lesions & mucosal erosions as a paraneoplastic syndrome.

PMID- 25857511
TI  - Testicular seminoma with early carcinomatous differentiation.

PMID- 25857512
TI  - Detection of bacterial contamination in apheresis platelets: is apheresis
      technology a factor?
AB  - BACKGROUND: Apheresis platelet (AP) contamination may be influenced by
      manufacturing methods because bacteria are subject to the same forces that permit
      separation of blood cells. This study assesses whether apheresis technology
      influences in-process detection of bacterial contamination. STUDY DESIGN AND
      METHODS: Blood Systems, Inc. (BSI) and New York Blood Center (NYBC) use Amicus
      and Trima devices to collect APs. Manufacturing (arm disinfection and in-line
      diversion) was consistent for both devices in the study period. Detection was
      performed using BacT/ALERT. True-positive (TP) rates were calculated and
      significance testing was performed using chi-square tests separately for BSI and
      NYBC. For BSI, multivariable logistic regression analysis was also performed to
      identify factors associated with TP results. RESULTS: For BSI, there were 49 TPs
      in 354,946 donations (1.4/10,000): 2.5 per 10,000 for Amicus and 1.0 per 10,000
      for Trima (p < 0.05). Multivariable logistic regression analysis showed
      significant association between TP and devices (odds ratio, 2.8; 95% confidence
      interval [CI], 1.01-8.0) and for one collection region. For NYBC, there were 18
      TPs in 161,840 donations (1.1/10,000): 2.1 per 10,000 for Amicus and 0.4 per
      10,000 for Trima (p < 0.05). CONCLUSIONS: The TP rate was significantly higher in
      Amicus collections than in Trima collections at NYBC and BSI. These results do
      not allow for conclusions regarding the relative clinical risk of PLTs collected
      by Amicus and Trima. Future evaluations of component quality and clinical
      outcomes should consider different collection technologies.

PMID- 25857513
TI  - Adverse reactions in horses that underwent general anesthesia and cervical
      myelography.
AB  - BACKGROUND: The study was prompted by a perceived high prevalence of myelographic
      complications varying in severity and type, and attributed to the contrast
      material or the procedure. HYPOTHESES: 1. Any adverse reaction (AAR) is
      associated with a change in CSF volume induced either by removal of CSF or
      addition of contrast material. 2. AAR occurs more frequently in horses with
      higher premyelography neurologic grade. 3. Nonspecific hyperthermia is attenuated
      by anti-inflammatory and osmotic agents. ANIMALS: Horses (n = 278) that underwent
      myelography between 2000 and 2012 at 5 institutions: A (87), B (68), C (65), D
      (46), and E (12). METHODS: Multi-institutional, retrospective, observational
      cross-sectional study. RESULTS: AAR were observed in 95/278 (34%) horses, were
      associated with longer general anesthesia time (P = .04) and higher contrast
      medium volume (P = .04); euthanasia because of AAR was performed in 5/278 (2%)
      horses. Adverse neurologic reactions were the most common type of complication
      observed occurring in 15/278 (5%) and 42/235 (18%) of horses in the intra- and
      postmyelography periods. A relationship between AAR and premyelography neurologic
      grade was not identified (P = .31). Nonspecific hyperthermia was observed in
      25/235 (11%) horses; no relationship was observed with administration of anti
      inflammatory drugs and osmotic agents (P = .30). CONCLUSIONS AND CLINICAL
      IMPORTANCE: The category of AAR occurred in one-third of the horses generally was
      mild and self-limiting. These reactions were associated with increased contrast
      medium volume and longer anesthesia time; but, no specific procedural
      recommendations could be made because of small odds ratios (OR) of <2 for each 1
      mL increase in contrast material and for each 1 minute of additional anesthesia
      time.

PMID- 25857514
TI  - Upper gastrointestinal physiology and diseases.
AB  - Nordic research on physiology and pathophysiology of the upper gastrointestinal
      tract has flourished during the last 50 years. Swedish surgeons and physiologists
      were in the frontline of research on the regulation of gastric acid secretion.
      This research finally led to the development of omeprazole, the first proton pump
      inhibitor. When Swedish physiologists developed methods allowing the assessment
      of acid secretion in isolated oxyntic glands and isolated parietal cells, the
      understanding of mechanisms by which gastric acid secretion is regulated took a
      great step forward. Similarly, in Trondheim, Norway, the acid producing isolated
      rat stomach model combined with a sensitive and specific method for determination
      of histamine made it possible to evaluate this regulation qualitatively as well
      as quantitatively. In Lund, Sweden, the identification of the enterochromaffin
      like cell as the cell taking part in the regulation of acid secretion by
      producing and releasing histamine was of fundamental importance both
      physiologically and clinically. Jorpes and Mutt established a center at
      Karolinska Institutet in Stockholm for the purification of gastrointestinal
      hormones in the 1960s, and Danes followed up this work by excelling in the field
      of determination and assessment of biological role of gastrointestinal hormones.
      A Finnish group was for a long period in the forefront of research on gastritis,
      and the authors' own studies on the classification of gastric cancer and the role
      of gastrin in the development of gastric neoplasia are of importance. It can,
      accordingly, be concluded that Nordic researchers have been central in the
      research on area of the upper gastrointestinal physiology and diseases. 

PMID- 25857515
TI  - Clinical Decision Support in the Management of Patients With Suspected Ebola
      Infection.
AB  - Patients with suspected public health threats, such as Ebola, must be quickly
      identified and isolated on presentation to health care facilities. Patients can
      be screened by intake staff or other health care providers; however, perfect
      compliance is difficult to achieve. Well-designed, carefully placed clinical
      decision support (CDS) within the electronic health record can be a reliable
      partner in helping to rapidly identify, isolate, and care for patients with
      suspected Ebola infection and other emerging public health threats. We describe
      how different types of CDS can be applied in the clinical workflow and share how
      we implemented CDS to force Ebola screening upon patient presentation to our
      emergency department.

PMID- 25857516
TI  - Relationship between IL28B gene rs8099917 polymorphism and SVR in Turkish
      patients with hepatitis C virus genotype 1.
AB  - BACKGROUND AND OBJECTIVE: The hepatitis C virus (HCV) which infects 3% of the
      world's population is a global challenge. Recently, genome-wide association
      studies (GWAS) have identified that the IL28B gene rs8099917 polymorphism was
      associated with the response to the pegylated-interferon alpha/ribavirin
      (PegIFNalpha/RBV) combination therapy in patients infected with HCV genotype 1.
      IL28B gene rs8099917 polymorphism should be determined before beginning treatment
      of HCV-infected patients to predict an individual's response. The aims of this
      study were to analyze the correlation between IL28B gene rs8099917 (T/G)
      polymorphism and PegIFNalpha/RBV therapy outcome in the Turkish population.
      METHODS: Genotypes of the IL28B gene rs8099917 (T/G) single nucleotide
      polymorphism (SNP) were determined in 308 patients with HCV infection by using a
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)
      assay. One group consisted of 148 patients with a sustained virological response
      (SVR), whereas the second group consisted of 160 nonresponders (non-SVR).
      RESULTS: Allele and genotype associations of IL28B gene rs8099917 polymorphism
      with a sustained virological response were observed in comparisons between the
      SVR and non-SVR groups (P<0.001). In addition, the characteristics of the
      subjects did not differ between these two groups except for age and fibrosis
      stage (P<0.05). Additionally, neither SVR nor rs80999917 genotypes were
      associated by HCV RNA levels. CONCLUSIONS: In conclusion, the rs8099917
      polymorphism was thus found strongly associated with a sustained virological
      response to therapy in Turkish patients infected with HCV genotype 1.
      Consequently, we suggest determining IL28B gene rs8099917 polymorphism of
      patients with HCV genotype 1 before onset of treatment.

PMID- 25857517
TI  - Body temperature sensitive micelles for MRI enhancement.
AB  - A novel thermo-sensitive micelle contrast agent and its enhancement of MRI
      contrast with temperature are reported. The morphology changes sharply near 37 
      degrees C, resulting in a significant amplification of the CEST signal. This
      enables detection of small changes in body temperature. 

PMID- 25857518
TI  - Use of genomic recursions and algorithm for proven and young animals for single
      step genomic BLUP analyses--a simulation study.
AB  - The purpose of this study was to examine accuracy of genomic selection via single
      step genomic BLUP (ssGBLUP) when the direct inverse of the genomic relationship
      matrix (G) is replaced by an approximation of G(-1) based on recursions for young
      genotyped animals conditioned on a subset of proven animals, termed algorithm for
      proven and young animals (APY). With the efficient implementation, this algorithm
      has a cubic cost with proven animals and linear with young animals. Ten duplicate
      data sets mimicking a dairy cattle population were simulated. In a first
      scenario, genomic information for 20k genotyped bulls, divided in 7k proven and
      13k young bulls, was generated for each replicate. In a second scenario, 5k
      genotyped cows with phenotypes were included in the analysis as young animals.
      Accuracies (average for the 10 replicates) in regular EBV were 0.72 and 0.34 for
      proven and young animals, respectively. When genomic information was included,
      they increased to 0.75 and 0.50. No differences between genomic EBV (GEBV)
      obtained with the regular G(-1) and the approximated G(-1) via the recursive
      method were observed. In the second scenario, accuracies in GEBV (0.76, 0.51 and
      0.59 for proven bulls, young males and young females, respectively) were also
      higher than those in EBV (0.72, 0.35 and 0.49). Again, no differences between
      GEBV with regular G(-1) and with recursions were observed. With the recursive
      algorithm, the number of iterations to achieve convergence was reduced from 227
      to 206 in the first scenario and from 232 to 209 in the second scenario. Cows can
      be treated as young animals in APY without reducing the accuracy. The proposed
      algorithm can be implemented to reduce computing costs and to overcome current
      limitations on the number of genotyped animals in the ssGBLUP method. 

PMID- 25857519
TI  - JMFT 2014 best article of the year award: whose baby is the most beautiful?

PMID- 25857524
TI  - Saxitoxin and the Ochre Sea Star: Molecule of Keystone Significance and a Classic
      Keystone Species.
AB  - Saxitoxins (STXs) are paralytic alkaloids produced by marine dinoflagellates in
      response to biotic and abiotic stressors yielding harmful algal blooms. Because
      STX impacts coastal, near-shore communities to a greater extent than would be
      predicted by its relative abundance, it has been referred to as a "molecule of
      keystone significance" in reference to Robert Paine's Keystone Species Concept.
      Pisaster ochraceus, the predator upon which Paine's concept was founded, inhabits
      waters regularly plagued by harmful algal blooms, but the effects of STX on
      Pisaster have not yet been investigated. Here, we used laboratory and field
      experiments to examine the potential consequences of exposure to STX on sea
      stars' feeding, attachment to the substrate, and success in fertilization.
      Pisaster exhibited similar feeding behaviors when offered non-toxic prey, STX
      containing prey, or a combination of the two. Although feeding behavior is
      unaffected, consumption of STX poses a physiological tradeoff. Sea stars in the
      laboratory and field had significantly lower thresholds of the force needed to
      detach them from their substrates after either being exposed to, or consuming,
      STX. High pressure (or high performance) liquid chromatography analysis indicated
      an accumulation of STX (and structural analogues) in sea stars' viscera, likely
      due to trophic transfer from toxic prey. Incidence of fertilization tended to
      decrease when gametes were exposed to high, yet ecologically relevant, STX
      concentrations of STX. These findings suggest that the molecule of keystone
      significance, STX, produced during harmful algal blooms extends its impacts to
      rocky intertidal communities by way of the keystone predator P. ochraceus. 

PMID- 25857525
TI  - Influence of Ambient Illumination on the Use of Olfactory and Visual Signals by a
      Nocturnal Hawkmoth During Close-Range Foraging.
AB  - As a goal-directed behavior, foraging for nectar functions on the basis of a
      sequence of innate stereotyped movements mainly regulated by sensory input. The
      operation of this inherited program is shaped by selective pressures acting on
      its efficiency, which is largely dependent upon the way the system handles
      sensory information. Flowers offer a wealth of signals, from odors acting as
      distant attractants, to colors eliciting approximation and feeding responses, to
      textures guiding feeding responses toward a reservoir of nectar. Thus, animals
      use different signals in the regulation of particular motor outputs.
      Nevertheless, the use of these sensory signals can be user-specific (e.g.
      species, motivation, experience, learning) as well as context-dependent (e.g.
      spatiotemporal patterns of stimulation, availability of signals, multimodal
      integration). The crepuscular/nocturnal hawkmoths Manduca sexta experience a wide
      range of illuminations during their foraging activity, which raises the question
      of how these environmental changes might affect the use of two important floral
      signals, odor and visual display. In a flight cage, we explored the use of these
      signals under different illuminances. Under conditions of starlight and crescent
      moonlight, moths showed very low levels of responsiveness to unscented feeders
      (artificial flowers). However, responsiveness was recovered either by increasing
      illumination, or by offering olfactory signals. Additionally, we recorded a bias
      toward white over blue feeders under dim conditions, which disappeared with
      increasing illumination. We discuss how this kind of experimental manipulation
      may provide insights to the study of how innate behavioral programs, and their
      underlying neural substrates, overcome selective forces imposed by the
      uncertainty of natural, ever-changing environments. 

PMID- 25857523
TI  - Mitochondrial function provides instructive signals for activation-induced B-cell
      fates.
AB  - During immune reactions, functionally distinct B-cell subsets are generated by
      stochastic processes, including class-switch recombination (CSR) and plasma cell
      differentiation (PCD). In this study, we show a strong association between
      individual B-cell fates and mitochondrial functions. CSR occurs specifically in
      activated B cells with increased mitochondrial mass and membrane potential, which
      augment mitochondrial reactive oxygen species (mROS), whereas PCD occurs in cells
      with decreased mitochondrial mass and potential. These events are consequences of
      initial slight changes in mROS in mitochondria(high) B-cell populations. In CSR
      committed cells, mROS attenuates haeme synthesis by inhibiting ferrous ion
      addition to protoporphyrin IX, thereby maintaining Bach2 function. Reduced mROS
      then promotes PCD by increasing haeme synthesis. In PCD-committed cells, Blimp1
      reduces mitochondrial mass, thereby reducing mROS levels. Identifying mROS as a
      haeme synthesis regulator increases the understanding of mechanisms regulating
      haeme homeostasis and cell fate determination after B-cell activation. 

PMID- 25857526
TI  - Distribution of Calcium and Chitin in the Tardigrade Feeding Apparatus in
      Relation to its Function and Morphology.
AB  - The cuticular portion of the tardigrade feeding apparatus is a complex structure
      that can be schematically divided into four parts: a buccal ring, a buccal tube,
      a stylet system (formed by two piercing stylets, each within a stylet coat, and
      two stylet supports), and the lining of a myoepithelial sucking pharynx. To
      better understand the function and evolution of the feeding apparatus, the morpho
      functional traits and chemical composition of the structures forming the feeding
      apparatuses of eight different species of tardigrades were analyzed. These eight
      species are representative of almost all main phylogenetic lineages of the
      phylum. The calcium and chitin in the feeding apparatus were examined by light
      microscopy, scanning electron microscopy, confocal laser scanning microscopy,
      energy dispersive X-ray spectroscopy, and Raman microspectroscopy (Raman). In all
      species, the feeding apparatus had been subjected to biomineralization due to
      CaCO3 encrustations organized in the crystalline form of aragonite. Aragonite and
      chitin are present in different concentrations in the feeding apparatus according
      to the structures and species considered. Generally, where the structures are
      rigid there is more aragonite than chitin, and vice versa. The buccal tube and
      piercing stylets are rich in calcium, with the piercing stylets apparently
      composed exclusively of aragonite. In eutardigrades, chitin is in higher
      concentration in the structures subject to higher mechanical stresses, such as
      the crests of the buccal crown and the condyles of the stylet furca. 

PMID- 25857527
TI  - Encapsulation of GFP in Complex Coacervate Core Micelles.
AB  - Protein encapsulation with polymers has a high potential for drug delivery,
      enzyme protection and stabilization. Formation of such structures can be achieved
      by the use of polyelectrolytes to generate so-called complex coacervate core
      micelles (C3Ms). Here, encapsulation of enhanced green fluorescent protein (EGFP)
      was investigated using a cationic-neutral diblock copolymer of two different
      sizes: poly(2-methyl-vinyl-pyridinium)41-b-poly(ethylene-oxide)205 and poly(2
      methyl-vinyl-pyridinium)128-b-poly(ethylene-oxide)477. Dynamic light scattering
      and fluorescence correlation spectroscopy (FCS) revealed a preferred micellar
      composition (PMC) with a positive charge composition of 0.65 for both diblock
      copolymers and micellar hydrodynamic radii of approximately 34 nm. FCS data show
      that at the PMC, C3Ms are formed above 100 nM EGFP, independent of polymer
      length. Mixtures of EGFP and nonfluorescent GFP were used to quantify the amount
      of GFP molecules per C3M, resulting in approximately 450 GFPs encapsulated per
      micelle. This study shows that FCS can be successfully applied for the
      characterization of protein-containing C3Ms. 

PMID- 25857528
TI  - Local conformational switching of supramolecular networks at the solid/liquid
      interface.
AB  - We use the electric field in a scanning tunneling microscope to manipulate the
      transition between open and close packed 2D supramolecular networks of neutral
      molecules in nonpolar media. We found that while the magnitude of the applied
      field is not decisive, it is the sign of the polarization that needs to be
      maintained to select one particular polymorph. Moreover, the switching is
      independent of the solvent used and fully reversible. We propose that the
      orientation of the surface dipole determined by the electric field might favor
      different conformation-depended charge transfer mechanisms of the adsorbates to
      the surface, inducing open (closed) structures for negative (positive)
      potentials. Our results show the use of local fields to select the polymorphic
      outcome of supramolecular assemblies at the solid/liquid interface. The effect
      has potential to locally control the capture and release of analytes in host
      guest systems and the 2D morphology in multicomponent layers. 

PMID- 25857529
TI  - Editorial Comment.

PMID- 25857530
TI  - Re: The Impact of Bleomycin on Retroperitoneal Histology at Post-Chemotherapy
      Retroperitoneal Lymph Node Dissection of Good Risk Germ Cell Tumors: K. C. Cary,
      J. A. Pedrosa, H. Z. Kaimakliotis, T. A. Masterson, L. H. Einhorn and R. S.
      Foster J Urol 2015;193:507-512.

PMID- 25857531
TI  - Re: Novel Bladder Preservation Therapy with Osaka Medical College Regimen: H.
      Azuma, T. Inamoto, K. Takahara, H. Nomi, H. Hirano, N. Ibuki, H. Uehara, K.
      Komura, K. Minami, T. Uchimoto, K. Saito, T. Takai, N. Tanda, K. Yamamoto, Y.
      Narumi and S. Kiyama J Urol 2015;193:443-450.

PMID- 25857534
TI  - A stable JAZ protein from peach mediates the transition from outcrossing to self
      pollination.
AB  - BACKGROUND: Variations in floral display represent one of the core features
      associated with the transition from allogamy to autogamy in angiosperms. The
      promotion of autogamy under stress conditions suggests the potential involvement
      of a signaling pathway with a dual role in both flower development and stress
      response. The jasmonic acid (JA) pathway is a plausible candidate to play such a
      role because of its involvement in many plant responses to environmental and
      developmental cues. In the present study, we used peach (Prunus persica L.)
      varieties with showy and non-showy flowers to investigate the role of JA (and JA
      signaling suppressors) in floral display. RESULTS: Our results show that PpJAZ1,
      a component of the JA signaling pathway in peach, regulates petal expansion
      during anthesis and promotes self-pollination. PpJAZ1 transcript levels were
      higher in petals of the non-showy flowers than those of showy flowers at
      anthesis. Moreover, the ectopic expression of PpJAZ1 in tobacco (Nicotiana
      tabacum L.) converted the showy, chasmogamous tobacco flowers into non-showy,
      cleistogamous flowers. Stability of PpJAZ1 was confirmed in vivo using PpJAZ1-GFP
      chimeric protein. PpJAZ1 inhibited JA-dependent processes in roots and leaves of
      transgenic plants, including induction of JA-response genes to mechanical
      wounding. However, the inhibitory effect of PpJAZ1 on JA-dependent fertility
      functions was weaker, indicating that PpJAZ1 regulates the spatial localization
      of JA signaling in different plant organs. Indeed, JA-related genes showed
      differential expression patterns in leaves and flowers of transgenic plants.
      CONCLUSIONS: Our results reveal that under stress conditions - for example,
      herbivore attacks - stable JAZ proteins such as PpJAZ1 may alter JA signaling in
      different plant organs, resulting in autogamy as a reproductive assurance
      mechanism. This represents an additional mechanism by which plant hormone
      signaling can modulate a vital developmental process in response to stress.

PMID- 25857536
TI  - A novel function for Wnt signaling modulating neuronal firing activity and the
      temporal structure of spontaneous oscillation in the entorhinal-hippocampal
      circuit.
AB  - During early and late postnatal developments, the establishment of functional
      neuronal connectivity depends on molecules like Wnt that help the recently formed
      synapses to establish and consolidate their new cellular interactions. However,
      unlike other molecules, whether Wnt can modulate the firing properties of cells
      is unknown. Here, for the first time we explore the physiological effect of the
      canonical and non-canonical Wnt pathways on a circuit that is currently
      generating oscillatory activity, the entorhinal cortex-hippocampal circuit. Our
      results indicate that Wnt pathways have strong influence in the circuital and
      cellular properties depending on the Wnt protein isoforms, concentration, and
      type of neuronal circuit. Antibodies against canonical and non-canonical ligands,
      as well as WASP-1 and sFRP-2, demonstrate that constitutive release of Wnts
      contributes to the maintenance of the network and intrinsic properties of the
      circuit. Furthermore, we found that the excess of Wnt3a or the permanent
      intracellular activation of the pathway with BIO-6 accelerates the period of the
      oscillation by disrupting the oscillatory units (Up states) in short units,
      presumably by affecting the synaptic mechanisms that couples neurons into the
      oscillatory cycle, but without affecting the spike generation. Instead, low doses
      of Wnt5a increase the period of the oscillation in EC by incorporating new cells
      into the network activity, probably modifying firing activity in other places of
      the circuit. Moreover, we found that Wnt signaling operates under different
      principles in the hippocampus. Using pyrvinium pamoate, a Wnt/beta-catenin
      dependent pathway inhibitor, we demonstrated that this pathway is essential to
      keep the firing activity in the circuit CA3, and in less degree of CA1 circuit.
      However, CA1 circuit possesses homeostatic mechanisms to up-regulate the firing
      activity when it has been suppressed in CA3, and to down-modulate the cellular
      excitability when exacerbated circuital activity has dominated. In summary, the
      amount of Wnt that is being released can exert a fine tuning of the physiological
      output, modulating firing activity, improving reliability of communication
      between neurons, and maintaining a continuous self-regulatory cycle of synaptic
      structure-function that can be present during all postnatal life. 

PMID- 25857535
TI  - Barriers to antiretroviral treatment initiation in rural KwaZulu-Natal, South
      Africa.
AB  - OBJECTIVES: Although antiretroviral therapy (ART) has been freely available since
      2004 in South Africa, not all those who are eligible initiate ART. We aimed to
      investigate individual and household characteristics as barriers to ART
      initiation in men and women in rural KwaZulu-Natal. METHODS: Adults >= 16 years
      old living within a sociodemographic surveillance area (DSA) who accessed the
      local HIV programme between 2007 and 2011 were included in the study. Individual
      and household factors associated with ART initiation within 3 months of becoming
      eligible for ART were investigated using multivariable logistic regression
      stratified by sex and after exclusion of individuals who died before initiating
      ART. RESULTS: Of the 797 men and 1598 women initially included, 8% and 5.5%,
      respectively, died before ART initiation and were excluded from further analysis.
      Of the remaining 733 men and 1510 women, 68.2% and 60.2%, respectively, initiated
      ART <= 3 months after becoming eligible (P = 0.34 after adjustment for CD4 cell
      count). In men, factors associated with a higher ART initiation rate were being a
      member of a household located < 2 km from the nearest HIV clinic and being
      resident in the DSA at the time of ART eligibility. In women, ART initiation was
      more likely in those who were not pregnant, in members of a household where at
      least one person was on ART and in those with a high wealth index. CONCLUSIONS:
      In this rural South African setting, barriers to ART initiation differed for men
      and women. Supportive individual- and household-level interventions should be
      developed to guarantee rapid ART initiation taking account gender specificities.

PMID- 25857537
TI  - Fabrication and characterization of optogenetic, multi-strip cardiac muscles.
AB  - Cardiac tissue engineering aims to recreate functional tissue constructs similar
      to the structure and function of the native myocardium. To date, in vitro tissue
      constructs lack the architectural complexity of a vascular network and the
      precise motor unit control of muscle fibers. Here, we present a method to
      construct engineered multi-strip cardiac muscle that simulates the bundle-like
      architecture of the native myocardium. Densely packed primary myocytes and
      cardiac fibroblasts were co-cultured with optogenetic, non-excitable cells. The
      resulting 3D syncytium triggered contraction upon localized blue light
      illumination to selectively activate and pace the multi-strip cardiac muscles,
      similar to the activity of pacemaker cells. Acting on a single load, we
      demonstrated graded force production through light-modulated multi-strip
      recruitment. These results demonstrate an in vitro platform of optogenetic, multi
      strip cardiac muscles that can be used in a wide variety of applications, such as
      drug discovery, tissue engineering, and bio-hybrid robotic systems. 

PMID- 25857538
TI  - Effects of fatiguing unilateral plantar flexions on corticospinal and
      transcallosal inhibition in the primary motor hand area.
AB  - BACKGROUND: Corticospinal excitability of the primary motor cortex (M1)
      representing the hand muscle is depressed by bilateral lower limb muscle fatigue.
      The effects of fatiguing unilateral lower limb contraction on corticospinal
      excitability and transcallosal inhibition in the M1 hand areas remain unclear.
      The purpose of this study was to determine the effects of fatiguing unilateral
      plantar flexions on corticospinal excitability in the M1 hand areas and
      transcallosal inhibition originated from the M1 hand area contralateral to the
      fatigued ankle. METHODS: Ten healthy volunteers (26.2 +/- 3.8 years) participated
      in the study. Using transcranial magnetic stimulation, we examined motor evoked
      potentials (MEPs) and interhemispheric inhibition (IHI) recorded from resting
      first dorsal interosseous (FDI) muscles before, immediately after, and 10 min
      after fatiguing unilateral lower limb muscle contraction, which was consisted of
      40 unilateral maximal isometric plantar flexions intermittently with a 2-s
      contraction followed by 1 s of rest. RESULTS: We demonstrated no significant
      changes in MEPs in the FDI muscle ipsilateral to the fatigued ankle and decrease
      in IHI from the M1 hand area contralateral to the fatigued ankle to the
      ipsilateral M1 hand area after the fatiguing contraction. MEPs in the FDI muscle
      contralateral to the fatigued ankle were increased after the fatiguing
      contraction. CONCLUSIONS: These results suggest that fatiguing unilateral lower
      limb muscle contraction differently influences corticospinal excitability of the
      contralateral M1 hand area and IHI from the contralateral M1 hand area to the
      ipsilateral M1 hand area. Although fatiguing unilateral lower limb muscle
      contraction increases corticospinal excitability of the ipsilateral M1 hand area,
      the increased corticospinal excitability is not associated with the decreased
      IHI.

PMID- 25857539
TI  - Nanofluid of zinc oxide nanoparticles in ionic liquid for single drop liquid
      microextraction of fungicides in environmental waters prior to high performance
      liquid chromatographic analysis.
AB  - Using a nanofluid obtained by dispersing ZnO nanoparticles (ZnO NPs) in 1-hexyl-3
      methylimidazolium hexafluorophosphate, new single drop microextraction method was
      developed for simultaneous extraction of three fungicides (chlorothalonil,
      kresoxim-methyl and famoxadone) in water samples prior to their analysis by high
      performance liquid chromatography (HPLC-VWD). The parameters affecting the
      extraction efficiency such as amount of ZnO NPs in the nanofluid, solvent volume,
      extraction time, stirring rate, pH and ionic strength of the sample solution were
      optimized. Under the optimized conditions, the limits of detection were in the
      range of 0.13-0.19ng/mL, the precision of the method assessed with intra-day and
      inter-day relative standard deviations were <4.82% and <7.04%, respectively. The
      proposed method was successfully applied to determine the three fungicides in
      real water samples including lake water, river water, as well as effluent and
      influent of wastewater treatment plant, with recoveries in the range of 74.94
      96.11% at 5ng/mL spiking level. Besides to being environmental friendly, the high
      enrichment factor and the data quality obtained with the proposed method
      demonstrated its potential for application in multi residue analysis of
      fungicides in actual water samples. 

PMID- 25857540
TI  - Adsorption of immunoglobulin Y in supermacroporous continuous cryogel with
      immobilized Cu(2+) ions.
AB  - The influence of temperature, pH and ionic strength on the adsorption of
      Immunoglobulin Y (IgY) in IDA-Cu(2+) cryogel system was studied by batch
      equilibrium measurements. The adsorptive equilibrium data were obtained at 17 and
      27 degrees C, pH 5.0 and 6.5, and at ionic strength of 50 and 200mmolL(-1) NaCl.
      Langmuir, Freundlich and Langmuir-Freundlich models were fitted to equilibrium
      data, while the enthalpy of adsorption of IgY in IDA-Cu(2+) cryogel system was
      calculated through Van't Hoff analysis. The binding of IgY on cryogel was
      stronger at 27 degrees C and lowest pH and ionic strength values, with apparent
      maximum adsorption capacity of 27mgg(-1). The adsorption of protein in the resin
      was spontaneous in all analyzed cases. The results provide valuable information
      to enable the improvement of IgY purification processes. 

PMID- 25857541
TI  - Improving the quality of biomarker candidates in untargeted metabolomics via peak
      table-based alignment of comprehensive two-dimensional gas chromatography-mass
      spectrometry data.
AB  - The potential of high-resolution analytical technologies like GC*GC/TOF MS in
      untargeted metabolomics and biomarker discovery has been limited by the
      development of fully automated software that can efficiently align and extract
      information from multiple chromatographic data sets. In this work we report the
      first investigation on a peak-by-peak basis of the chromatographic factors that
      impact GC*GC data alignment. A representative set of 16 compounds of different
      chromatographic characteristics were followed through the alignment of 63 GC*GC
      chromatograms. We found that varying the mass spectral match parameter had a
      significant influence on the alignment for poorly-resolved peaks, especially
      those at the extremes of the detector linear range, and no influence on well
      chromatographed peaks. Therefore, optimized chromatography is required for proper
      GC*GC data alignment. Based on these observations, a workflow is presented for
      the conservative selection of biomarker candidates from untargeted metabolomics
      analyses. 

PMID- 25857542
TI  - Extending analysis of environmental pollutants in human urine towards screening
      for suspected compounds.
AB  - Today there is a large difference in the number of chemicals of commerce and the
      number of chemicals being monitored in environmental and human samples. During
      the last decades suspect screening methods have been developed to increase the
      number of monitored analytes. Peaks detected during high resolution mass
      spectrometry full scan measurements are compared to a list of suspect chemicals
      with known exact masses. These methods, however, have so far focused on
      environmental samples. Thus we present a method development for a suspect
      screening of human urine samples. The sample preparation techniques and
      instrumental analysis were tested by target chemicals with a wide range of
      properties. A combination of direct injection and QuEChERS extraction followed by
      liquid chromatography coupled to high resolution mass spectrometry was able to
      detect 33 of the 40 spiked target compounds at 30-120% absolute recovery. For
      suspect evaluation peaks were deconvoluted and aligned with the software MZmine
      followed by R script processing. Comparing detected and in-silico fragmentation,
      nine suspect chemicals could be tentatively identified in a pooled human urine
      sample and four of these were confirmed by a reference standard. 

PMID- 25857543
TI  - Simple and sensitive determination of hydrazine in drinking water by ultra-high
      performance liquid chromatography-tandem mass spectrometry after derivatization
      with naphthalene-2,3-dialdehyde.
AB  - An ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS)
      method was developed to determine the level of hydrazine in drinking water. The
      method is based on the derivatization of hydrazine with naphthalene-2,3
      dicarboxaldehyde (NDA) in water. The optimum conditions for UPLC-MS/MS detection
      were determined as follows: derivatization reagent dosage, 50mg/L of NDA; pH 2;
      and reaction time, 1min; room temperature. The formed derivative was injected
      into an LC system without extraction or purification procedures. Under the
      established conditions, the method was used to detect hydrazine in raw drinking
      water and chlorinated drinking water. The limits of detection and quantification
      for hydrazine in drinking water were 0.003MUg/L and 0.01MUg/L, respectively. The
      accuracy was in the range of 97-104%, and precision, expressed as relative
      standard deviation, was less than 9% in drinking water. Hydrazine was detected at
      a concentration of 0.13MUg/L in one sample among 24 raw drinking water samples
      and in a range of 0.04-0.45MUg/L in three samples among 24 chlorinated drinking
      water samples. 

PMID- 25857544
TI  - Dissolution of biological samples in deep eutectic solvents: an approach for
      extraction of polycyclic aromatic hydrocarbons followed by liquid chromatography
      fluorescence detection.
AB  - A novel sample preparation method based on the complete dissolution of marine
      biological samples in choline chloride-oxalic acid (ChCl-Ox) deep eutectic
      solvent was developed for fast and efficient extraction of eight polycyclic
      aromatic hydrocarbons (PAHs) using minimum volumes of cyclohexane. The extracted
      PAHs were purified and then measured by high-performance liquid chromatography
      fluorescence detection (HPLC-FL). The effect of key parameters on extraction
      recoveries and precision was investigated. At optimized conditions, the studied
      samples were dissolved under atmospheric pressure in ChCl-Ox (1:2) at 55 degrees
      C for 30min, which is considerably lower than the temperature used in the
      classical and current methods. After dissolution, it took approximately 20min to
      quantitatively extract the PAHs from ChCl-Ox using 5mL cyclohexane. Depending on
      the analyte, the developed method was linear over the calibration range 1.0-250,
      2.0-250, and 5.0-250ngg(-1), with r(2)>0.996. The detection limits of the method
      were between 0.50 and 3.08ngg(-1). The intra-day and inter-day precisions (based
      on the relative standard deviation, n=5) of the spiked PAHs at a concentration
      level of 50ngg(-1) were better than 12.6% and 13.3%, respectively. Individual PAH
      recoveries from spiked marine fish and macroalgae samples were in the range of
      71.6% to 109.6%. For comparison, the spiked samples were also subjected to the
      Soxhlet extraction method. The simplicity of the procedure, high extraction
      efficiency, short analysis time, and use of safe and inexpensive components
      suggest the proposed method has a high potential for utilization in routine trace
      PAH analysis in biological samples. 

PMID- 25857545
TI  - Full-surface deformation measurement of anisotropic tissues under indentation.
AB  - Inverse finite element-based analysis of soft biological tissues is an important
      tool to investigate their complex mechanical behavior and to develop physical
      models for medical simulations. Although there have recently been advances in
      dealing with the computational complexities of modeling biological materials, the
      collection of a sufficiently dense set of experimental data to properly capture
      their typically regionally varying properties still remains a critical issue. The
      aim of this work was to develop and test an optical system that combines 2D
      Digital Image Correlation (DIC) and a novel Fringe Projection method with radial
      sensitivity (RFP) to test soft biological tissues under in vitro indentation.
      This system has the distinctive capability of using a single camera to retrieve
      the shape and 3D deformation of the whole upper surface of the indented sample
      without any blind measurement areas (with exception of the area under the
      indenter), with nominal depth and in-plane resolution of 0.05 mm and 0.004 mm,
      respectively. To test and illustrate the capabilities of the developed DIC/RFP
      system, the in vitro response to indentation of a homogeneous and isotropic latex
      foam is presented against the response of a slab of porcine ventricular
      myocardium, a highly in-homogeneous and anisotropic tissue. Our results
      illustrate the enhanced capabilities of the developed method to capture asymmetry
      in deformation with respect to standard indentation tests. This feature, together
      with the possibility of miniaturizing the system into a hand-held probe, makes
      this method potentially extendable to in vivo settings, alone or in combination
      with ultrasound measurements. 

PMID- 25857546
TI  - Accuracy and Test-Retest Reproducibility of Two-Dimensional Knowledge-Based
      Volumetric Reconstruction of the Right Ventricle in Pulmonary Hypertension.
AB  - BACKGROUND: Right heart function is the key determinant of symptoms and prognosis
      in pulmonary hypertension (PH), but the right ventricle has a complex geometry
      that is challenging to quantify by two-dimensional (2D) echocardiography. A novel
      2D echocardiographic technique for right ventricular (RV) quantitation involves
      knowledge-based reconstruction (KBR), a hybrid of 2D echocardiography-acquired
      coordinates localized in three-dimensional space and connected by reference to a
      disease-specific RV shape library. The aim of this study was to determine the
      accuracy of 2D KBR against cardiac magnetic resonance imaging in PH and the test
      retest reproducibility of both conventional 2D echocardiographic RV fractional
      area change (FAC) and 2D KBR. METHODS: Twenty-eight patients with PH underwent
      same-day echocardiography and cardiac magnetic resonance imaging. Two operators
      performed serial RV FAC and 2D KBR acquisition and postprocessing to assess inter
      and intraobserver test-retest reproducibility. RESULTS: Bland-Altman analysis
      (mean bias +/- 95% limits of agreement) showed good agreement for end-diastolic
      volume (3.5 +/- 25.0 mL), end-systolic volume (0.9 +/- 19.9 mL), stroke volume
      (2.6 +/- 23.1 mL), and ejection fraction (0.4 +/- 10.2%) measured by 2D KBR and
      cardiac magnetic resonance imaging. There were no significant interobserver or
      intraobserver test-retest differences for 2D KBR RV metrics, with acceptable
      limits of agreement (interobserver end-diastolic volume, -0.9 +/- 21.8 mL; end
      systolic volume, -1.3 +/- 25.8 mL; stroke volume, -0.2 +/- 24.2 mL; ejection
      fraction, 0.7 +/- 14.4%). Significant test-retest variability was observed for 2D
      echocardiographic RV areas and FAC. CONCLUSIONS: Two-dimensional KBR is an
      accurate, novel technique for RV volumetric quantification in PH, with superior
      test-retest reproducibility compared with conventional 2D echocardiographic RV
      FAC.

PMID- 25857547
TI  - Doppler Imaging in Aortic Stenosis: The Importance of the Nonapical Imaging
      Windows to Determine Severity in a Contemporary Cohort.
AB  - BACKGROUND: Although the highest aortic valve velocity was thought to be obtained
      from imaging windows other than the apex in about 20% of patients with severe
      aortic stenosis (AS), its occurrence appears to be increasing as the age of
      patients has increased with the application of transcatheter aortic valve
      replacement. The aim of this study was to determine the frequency with which the
      highest peak jet velocity (Vmax) is found at each imaging window, the degree to
      which neglecting nonapical imaging windows underestimates AS severity, and
      factors influencing the location of the optimal imaging window in contemporary
      patients. METHODS: Echocardiograms obtained in 100 consecutive patients with
      severe AS from January 3 to May 23, 2012, in which all imaging windows were
      interrogated, were retrospectively analyzed. AS severity (aortic valve area and
      mean gradient) was calculated on the basis of the apical imaging window alone and
      the imaging window with the highest peak jet velocity. The left ventricular
      aortic root angle measured in the parasternal long-axis view as well as clinical
      variables were correlated with the location of highest peak jet velocity.
      RESULTS: Vmax was most frequently obtained in the right parasternal window (50%),
      followed by the apex (39%). Subjects with acute angulation more commonly had Vmax
      at the right parasternal window (65% vs 43%, P = .05) and less commonly had Vmax
      at the apical window (19% vs 48%, P = .005), but Vmax was still located outside
      the apical imaging window in 52% of patients with obtuse aortic root angles. If
      nonapical windows were neglected, 8% of patients (eight of 100) were
      misclassified from high-gradient severe AS to low-gradient severe AS, and another
      15% (15 of 100) with severe AS (aortic valve area < 1.0 cm(2)) were misclassified
      as having moderate AS (aortic valve area > 1.0 cm(2)). CONCLUSIONS: In this
      contemporary cohort, Vmax was located outside the apical imaging window in 61% of
      patients, and neglecting the nonapical imaging windows resulted in the
      misclassification of AS severity in 23% of patients. Aortic root angulation as
      measured by two-dimensional echocardiography influences the location of Vmax
      modestly. Despite increasing time constraints on many echocardiography
      laboratories, these data confirm that routine Doppler interrogation from multiple
      imaging windows is critical to accurately determine the severity of AS in
      contemporary clinical practice.

PMID- 25857548
TI  - Efficacy-effectiveness gap as an obstacle to translating clinical trials to
      clinical practice.

PMID- 25857549
TI  - Population based study on sentinel node biopsy before or after neoadjuvant
      chemotherapy in clinically node negative breast cancer patients: Identification
      rate and influence on axillary treatment.
AB  - The timing of the sentinel lymph node biopsy (SNB) is controversial in clinically
      node negative patients receiving neoadjuvant chemotherapy (NAC). We studied
      variation in the timing of axillary staging in breast cancer patients who
      received NAC and the subsequent axillary treatment in The Netherlands. Patients
      diagnosed with clinically node negative primary breast cancer between 1st January
      2010 and 30th June 2013 who received NAC and SNB were selected from the
      Netherlands Cancer Registry. Data on patient and tumour characteristics, axillary
      staging and treatment were analysed. Two groups were defined: (1) patients with
      SNB before NAC (N=980) and (2) patients with SNB after NAC (N=203). Eighty-three
      percent of patients underwent SNB before NAC, with large regional variation (35
      99%). The SN identification rate differed for SNBs conducted before and after NAC
      (98% versus 95%; p=0.032). A lower proportion of patients had a negative SNB when
      assessed before NAC compared to after (54% versus 67%; p=0.001). The proportion
      of patients receiving any axillary treatment was higher for those with SNB before
      NAC than after (45% versus 33%; p=0.006). In conclusion, variation exists in the
      timing of SNB in clinical practice in The Netherlands for clinically node
      negative breast cancer patients receiving NAC. The post-NAC SN procedure is,
      despite some lower SN identification rate, associated with a significantly less
      frequent axillary treatment and thus with less expected morbidity. The effect on
      recurrence rate is not yet clear. Patients in this registry will be followed
      prospectively for long-term outcome. 

PMID- 25857551
TI  - Neuronal stress signaling and eIF2alpha phosphorylation as molecular links
      between Alzheimer's disease and diabetes.
AB  - Mounting evidence from clinical, epidemiological, neuropathology and preclinical
      studies indicates that mechanisms similar to those leading to peripheral
      metabolic deregulation in metabolic disorders, such as diabetes and obesity, take
      place in the brains of Alzheimer's disease (AD) patients. These include pro
      inflammatory mechanisms, brain metabolic stress and neuronal insulin resistance.
      From a molecular and cellular perspective, recent progress has been made in
      unveiling novel pathways that act in an orchestrated way to cause neuronal damage
      and cognitive decline in AD. These pathways converge to the activation of
      neuronal stress-related protein kinases and excessive phosphorylation of
      eukaryotic translation initiation factor 2alpha (eIF2alpha-P), which plays a key
      role in control of protein translation, culminating in synapse dysfunction and
      memory loss. eIF2alpha-P signaling thus links multiple neuronal stress pathways
      to impaired neuronal function and neurodegeneration. Here, we present a critical
      analysis of recently discovered molecular mechanisms underlying impaired brain
      insulin signaling and metabolic stress, with emphasis on the role of stress
      kinase/eIF2alpha-P signaling as a hub that promotes brain and behavioral
      impairments in AD. Because very similar mechanisms appear to operate in
      peripheral metabolic deregulation in T2D and in brain defects in AD, we discuss
      the concept that targeting defective brain insulin signaling and neuronal stress
      mechanisms with anti-diabetes agents may be an attractive approach to fight
      memory decline in AD. We conclude by raising core questions that remain to be
      addressed toward the development of much needed therapeutic approaches for AD. 

PMID- 25857552
TI  - Improving recruitment of older people to clinical trials: use of the cohort
      multiple randomised controlled trial design.
AB  - There is widespread evidence of under-recruitment of older people to research
      studies, notably randomised controlled trials of interventions. Study exclusion
      criteria, ethical dilemmas, patient preference, risk of bias and challenges for
      treatment comparisons are particular problems faced by researchers. This article
      describes how more widespread use of the cohort multiple randomised controlled
      trial (cmRCT) design in ageing research may help address many of these problems.
      The original key features of the cmRCT design are a large observational cohort of
      people with the condition of interest (e.g. frailty) with regular measurement of
      outcomes for the whole cohort. For each RCT eligible patients are identified and
      a random selection offered the trial intervention; their outcomes are compared
      with those eligible patients not offered the intervention. Relevant assents are
      obtained at baseline to enable future involvement in a range of potential trials.
      Where possible, the follow-up schedule is aligned with the key time points for
      assessment in future trials and includes the key baseline descriptors, and
      primary and secondary outcomes. The cmRCT approach also enables detailed
      observational and qualitative research for the chosen condition of interest, and
      might include the establishment of research biobanks to better align basic
      science, epidemiological, qualitative and clinical trial research. 

PMID- 25857553
TI  - Quantifying progression and regression of thrombotic risk in experimental
      atherosclerosis.
AB  - Currently, there are no generally applicable noninvasive methods for defining the
      relationship between atherosclerotic vascular damage and risk of focal
      thrombosis. Herein, we demonstrate methods to delineate the progression and
      regression of vascular damage in response to an atherogenic diet by quantifying
      the in vivo accumulation of semipermeable 200-300 nm perfluorocarbon core
      nanoparticles (PFC-NP) in ApoE null mouse plaques with [(19)F] magnetic resonance
      spectroscopy (MRS). Permeability to PFC-NP remained minimal until 12 weeks on
      diet, then increased rapidly following 12 weeks, but regressed to baseline within
      8 weeks after diet normalization. Markedly accelerated clotting (53.3% decrease
      in clotting time) was observed in carotid artery preparations of fat-fed mice
      subjected to photochemical injury as defined by the time to flow cessation. For
      all mice on and off diet, an inverse linear relationship was observed between the
      permeability to PFC-NP and accelerated thrombosis (P = 0.02). Translational
      feasibility for quantifying plaque permeability and vascular damage in vivo was
      demonstrated with clinical 3 T MRI of PFC-NP accumulating in plaques of
      atherosclerotic rabbits. These observations suggest that excessive permeability
      to PFC-NP may indicate prothrombotic risk in damaged atherosclerotic vasculature,
      which resolves within weeks after dietary therapy.

PMID- 25857554
TI  - Endothelial cell spheroids as a versatile tool to study angiogenesis in vitro.
AB  - Given the need for robust and cost-efficient in vitro models to study
      angiogenesis and reproducibly analyze potential pro- and antiangiogenic compounds
      in preclinical studies, we developed a 3-dimensional in vitro angiogenesis assay
      that is based on collagen gel-embedded, size-defined spheroids generated from
      cultured human umbilical vein endothelial cells (HUVECs). Despite its wide
      distribution, limitations, sensitivity, robustness, and improvements, the
      capacity of this assay for functional screening purposes has not been elucidated
      thus far. By using time-lapse video microscopy, we show that tip cells lead the
      formation of capillary-like and partially lumenized sprouts originating from the
      spheroids. Angiogenic sprouting from spheroids generated from 5 different primary
      cultured human endothelial cell types was induced by physiologic concentrations
      of vascular endothelial cell growth factor 165. Based on this assay system, we
      determined the capacity of 880 approved drugs to interfere with or boost
      angiogenic sprouting, thereby assessing their putative angiogenesis-related side
      effects or novel applications. However, although this assay allowed for a rapid
      and reproducible determination of functional IC50 values of individual compounds,
      the sprouting results were partially affected by the HUVEC passage number and
      donor variability. To overcome this limitation, immortalized HUVECs (iHUVECs)
      showing a more homogenous response in terms of proliferation and sprouting over
      multiple population doublings were used in the course of this study.
      Collectively, the spheroid-based angiogenesis assay provides a sensitive and
      versatile tool to study the impact of pro- and antiangiogenic determinants on
      multiple steps of the angiogenic cascade. It is compatible with different
      endothelial cell types and allows use of iHUVECs to improve its overall
      robustness.

PMID- 25857555
TI  - TNF-related apoptosis-inducing ligand promotes human preadipocyte proliferation
      via ERK1/2 activation.
AB  - Upon obesity, adipose tissue is excessively expanded and characterized by
      pathologic processes like hypoxia, fibrosis, and inflammation. Death ligands
      belonging to the TNF superfamily such as TNF-alpha are important contributors to
      these derangements and exert a pronounced influence on the metabolic and cellular
      homeostasis of adipose tissue. Here, we sought to identify the effect of the
      death ligand TNF-related apoptosis-inducing ligand (TRAIL) on the adipose tissue
      precursor cell pool and therefore investigated its influence on preadipocyte
      proliferation. Treatment of human preadipocytes with TRAIL resulted in a time-
      and dose-dependent increase in proliferation (EC50 3.4 ng/ml) comparable to IGF
      1. Although no apoptosis was observed, TRAIL triggered a rapid cleavage of
      caspase-8 and -3. Neither inhibition of caspase activity by zVAD.fmk (20 uM) nor
      ablation of caspase-8 expression by lentivirus-delivered small hairpin RNA
      (shRNA) abolished the proliferative response. TRAIL triggered a delayed and
      sustained activation of ERK1/2, leaving Akt, p38, JNK, and NF-kappaB unaffected.
      Importantly, inhibition of ERK1/2 activation by PD0325901 (300 nM) or AZD6244 (5
      or 10 uM) completely abolished the proliferative response. We thus reveal a
      hitherto unknown function of TRAIL in regulating adipose tissue homeostasis by
      promoting the proliferation of tissue-resident precursor cells.

PMID- 25857557
TI  - Cyclodextrin-peptide conjugates for sequence specific DNA binding.
AB  - Synthetic models of bZIP transcription factors have been developed with the
      capability of specific DNA recognition. Our design is based on the CuAAC mediated
      conjugation of basic region Leucine Zipper peptides to different derivatives of
      alpha, beta and gamma-cyclodextrins equipped with azide functionalities. Thorough
      optimization of reaction conditions allowed convergent and simultaneous
      conjugation of two long unprotected cationic peptides to cyclodextrin-bis azide
      derivatives. The resulting constructs were shown to specifically recognize their
      cognate DNA sequence with nM affinities. In comparison with previously developed
      TF models, the derivatives described here combine the enhanced DNA binding
      capabilities with an easy and convergent synthetic route. 

PMID- 25857556
TI  - A proton current associated with sour taste: distribution and functional
      properties.
AB  - Sour taste is detected by taste receptor cells that respond to acids through yet
      poorly understood mechanisms. The cells that detect sour express the protein
      PKD2L1, which is not the sour receptor but nonetheless serves as a useful marker
      for sour cells. By use of mice in which the PKD2L1 promoter drives expression of
      yellow fluorescent protein, we previously reported that sour taste cells from
      circumvallate papillae in the posterior tongue express a proton current. To
      establish a correlation between this current and sour transduction, we examined
      its distribution by patch-clamp recording. We find that the current is present in
      PKD2L1-expressing taste cells from mouse circumvallate, foliate, and fungiform
      papillae but not in a variety of other cells, including spinal cord neurons that
      express PKD2L1. We describe biophysical properties of the current, including pH
      dependent Zn(2+) inhibition, lack of voltage-dependent gating, and activation at
      modest pH values (6.5) that elicit action potentials in isolated cells.
      Consistent with a channel that is constitutively open, the cytosol of sour taste
      cells is acidified. These data define a functional signature for the taste cell
      proton current and indicate that its expression is mostly restricted to the
      subset of taste cells that detect sour.

PMID- 25857558
TI  - TB control requires new tools, policies, and delivery models.

PMID- 25857559
TI  - Mycobacterium Tuberculosis Biofilm - A new perspective.

PMID- 25857560
TI  - Endobronchial tuberculosis.
AB  - Endobronchial tuberculosis refers to tuberculous infection of the
      tracheobronchial tree. Diagnosis requires a high index of suspicion since
      symptoms are attributed to co-existing pulmonary tuberculosis and airway lesions
      are not detectable on chest radiograph. While computed tomography and
      bronchoscopy are useful for the evaluation of tracheobronchial stenosis or
      obstruction, goals of treatment remain in the eradication of tubercle bacilli and
      prevention of airway stenosis. Corticosteroids may halt progression of active
      disease to fibro-stenotic stage, however if tracheobronchial stenosis causing
      post-obstructive pneumonia, atelectasis and dyspnea has occurred, airway patency
      must be restored mechanically by surgery or bronchoscopic techniques. 

PMID- 25857561
TI  - Detection of drug resistance in Mycobacterium tuberculosis: Methods, principles
      and applications.
AB  - The growing emergence of multidrug resistant tuberculosis (MDR-TB) strains is
      obstructing efforts for the control and management of TB. Proper management of
      MDR-TB relies on early recognition of drug resistance followed by timely
      treatment initiation. Several diagnostic methods, both phenotypic and molecular,
      have been developed in last few years for rapid identification of drug resistant
      (DR)-TB. Revised national tuberculosis control programmes (RNTPs) may find it
      tough to choose from the puzzling variety of rapid tests. Here, we present an
      outline of the available methods, discussing their basis, advantages and
      deficiencies. 

PMID- 25857562
TI  - Isolation of Mycobacterium tuberculosis from sputum of tribal, non-tribal
      pulmonary tuberculosis patients of Andaman & Nicobar islands by conventional
      culture method and assessment of first line anti-tuberculosis drug susceptibility
      patterns.
AB  - BACKGROUND: Drug resistance surveys have not yet conducted in these Islands and
      as such no data exists on drug resistance currently. AIMS: the present study was
      initiated with the objective of isolation and assessment of Drug resistance
      patterns of Mycobacterium tuberculosis isolates from sputum specimens collected
      from different categories of Tribal, Non-Tribal pulmonary tuberculosis patients
      treated under DOTS and Non-DOTS program by conventional culture and Proportion
      sensitivity (PST) method to detect patients with Multidrug resistant strains.
      METHODS: The investigation was hospital based laboratory surveillance study
      carried out for a period of 3 years at the selected hospitals of Andaman district
      (TB ward GB Pant Hospital at Port Blair, CHC Bamboflat at Port Blair and CHC
      Rangat at Rangat) and Nicobar district (CHC Nancowry at Nancowry groups of
      Islands), among the new cases and re-treatment cases of tuberculosis patient
      under DOTS program and Non-DOTS patients attended selected hospitals of Andaman &
      Nicobar districts chosen for the study. RESULTS: 83 culture positive isolates
      obtained (74 identified as M. tuberculosis) from the sputum specimen of 162 cases
      of tuberculosis patient by conventional culture method. 60 M. tuberculosis
      isolates subjected to drug susceptibility test using PST method, 7 patients
      (11.67%) found to be Multidrug resistant tuberculosis (MDR-TB), resistant
      patterns were S + H + R + E = 1(Cat II-DOTS),H + r = 3(Cat-I DOTS = 1, Cat II
      DOTS-1,Non-DOTS = 1), Rifampicin resistant alone = 2 (Non-DOTS = 1, Cat II-DOTS =
      1) and R + E = 1(Cat I-DOTS). CONCLUSIONS: Laboratory finding suggested that nine
      MDR-TB strains detected in DOTS and Non-DOTS among 60 M. tuberculosis isolates
      were selected for drug susceptibility testing but two isolates detected as MDR-TB
      from patients was already on Second line drugs treatment were not included in the
      MDR-TB detection criteria. Hence 7 patients (11.67%) declared to be Multidrug
      resistant tuberculosis (MDR-TB). 2 MDR-TB strains with resistant patterns H + r =
      1(Cat II-DOTS), Rifampicin resistant alone = 1(Non-DOTS) detected from 12
      isolates of Tribal patients from Nicobar district and 5 MDR-TB strains with
      resistant patterns S + H + R + E = 1 (Cat II-DOTS), H + r = 2(Cat I-DOTS = 1,Non
      DOTS = 1), Rifampicin resistant alone = 1 (Cat II-DOTS) and R + E = 1(Cat I-DOTS)
      detected from 48 isolates of Non-Tribal patients from Andaman district. To assess
      the MDR-TB burden in the islands, systematic drug resistant surveillance study
      needs to be conducted.

PMID- 25857550
TI  - The ventral pallidum: Subregion-specific functional anatomy and roles in
      motivated behaviors.
AB  - The ventral pallidum (VP) plays a critical role in the processing and execution
      of motivated behaviors. Yet this brain region is often overlooked in published
      discussions of the neurobiology of mental health (e.g., addiction, depression).
      This contributes to a gap in understanding the neurobiological mechanisms of
      psychiatric disorders. This review is presented to help bridge the gap by
      providing a resource for current knowledge of VP anatomy, projection patterns and
      subregional circuits, and how this organization relates to the function of VP
      neurons and ultimately behavior. For example, ventromedial (VPvm) and
      dorsolateral (VPdl) VP subregions receive projections from nucleus accumbens
      shell and core, respectively. Inhibitory GABAergic neurons of the VPvm project to
      mediodorsal thalamus, lateral hypothalamus, and ventral tegmental area, and this
      VP subregion helps discriminate the appropriate conditions to acquire natural
      rewards or drugs of abuse, consume preferred foods, and perform working memory
      tasks. GABAergic neurons of the VPdl project to subthalamic nucleus and
      substantia nigra pars reticulata, and this VP subregion is modulated by, and is
      necessary for, drug-seeking behavior. Additional circuits arise from nonGABAergic
      neuronal phenotypes that are likely to excite rather than inhibit their targets.
      These subregional and neuronal phenotypic circuits place the VP in a unique
      position to process motivationally relevant stimuli and coherent adaptive
      behaviors. 

PMID- 25857563
TI  - Directly observed treatment short course for tuberculosis. What happens to them
      in the long term?
AB  - BACKGROUND: Though Directly Observed Treatment Short course (DOTS) is found
      effective in many controlled trials, few studies have examined its effectiveness
      under programmatic conditions. DOTS based Revised National TB Control Programme
      (RNTCP) was initiated in Ernakulam district of Kerala state in June 2000. It now
      covers all of India. It now seems appropriate to do an evaluation of RNTCP at
      field level. AIM: This study aims to document impact of DOTS in providing
      productive life to tuberculosis patients and measure rate of clinical recurrence
      under program conditions. METHODS: Retrospective cohort study using interview
      with structured, peer reviewed and validated questionnaire among cohort of new
      smear positive patients registered in RNTCP from January 2002 to December 2003
      and declared cured/Treatment completed. We have contacted 1173 patients (62.2% of
      the cohort) for the study at their homes by devising a strategy to identify and
      trace patients from address given in TB registers. RESULTS: Mean age of
      identified patients is 51.9 years. 82.4% were males. 79% patients report full
      supervision in the intensive period. After seven years 64.1% are healthy, work
      and earn; 29.8% report residual respiratory problems; 0.3% of symptomatic
      patients were diagnosed with smear positive pulmonary tuberculosis. Relapse
      calculated as worst case scenario for full target population (dead and migrated
      inclusive) is 9.27%. Age specific mortality is 4-6 times higher than in a
      comparable general population. CONCLUSIONS: DOTS treatment under program
      conditions makes a measurable reduction in tuberculosis morbidity. Though high
      proportion of patients remains productive after DOTS, a significant proportion
      complains of residual respiratory symptoms. Age specific mortality of Post
      tuberculosis patients is high compared to general population. Close follow up
      irrespective of duration of symptoms may help to determine the causes of high
      residual morbidity and mortality rates.

PMID- 25857564
TI  - Role of bronchoscopy in evaluation of cases with sputum smear negative pulmonary
      tuberculosis, interstitial lung disease and lung malignancy: A retrospective
      study of 712 cases.
AB  - BACKGROUND: The introduction of flexible bronchoscope has revolutionized the
      field of pulmonary medicine and is a standard instrument used for diagnostic
      purpose. A retrospective analysis of the clinico-radiological profile,
      indication, biopsy procedure and complications, for patients undergoing
      bronchoscopy at one of the respiratory unit at a tertiary care center in India.
      METHODS: Retrospective analysis of 712 bronchoscopies was done in regard to
      demographic profile, clinical and radiological presentation and diagnostic
      indication. The results were analyzed on basis of bronchoscopy inspection and
      histopathological specimen obtained from transbronchial (TBLB), endobronchial
      biopsy (EBLB) and cytology specimen by transbronchial needle aspiration (TBNA).
      Furthermore, diagnostic yield of each biopsy procedure and their combination was
      evaluated. RESULTS: Of 712 patients undergoing bronchoscopy, the pathological
      diagnosis was achieved in 384 (53.93%). Of 384 diagnosed cases, the clinic-radio
      pathological diagnosis of pulmonary tuberculosis in 88 (22.19%), interstitial
      lung disease (ILDs) in 226 (58.85%), and lung cancer in 70 (18.22%) cases. Of 116
      sputum smear negative tuberculosis patients, 88 (75.86%) were diagnosed to be
      pulmonary tuberculosis; the contribution of BAL being 71.59%. Of 226 ILDs,
      sarcoidosis was most common 148/226 (65.48%). Among 70 lung cancer diagnosed
      cases, squamous cell carcinoma was most common (54.28%). CONCLUSION: The results
      from current study reemphasizes on the diagnostic utility as well as safety of
      the bronchoscopy procedure.

PMID- 25857566
TI  - Rare interstitial lung disease: Pulmonary Langerhans Cell Histiocytosis in a
      young non smoking Indian female.
AB  - Adult Pulmonary Langerhans Cell Histiocytosis (PLCH) is a rare interstitial lung
      disease which occurs almost exclusively in smokers. A marked male predominance
      was initially reported, but recent studies show both men and women are equally
      affected due to the increasing smoking habits in women. The natural history is
      variable with 25% of patients having asymptomatic disease while 10-20% progress
      rapidly to respiratory insufficiency and death. The diagnosis is not easily
      recognized by clinicians or pathologists. Awareness of the clinical presentation
      and classical HRCT findings helps in early diagnosis and management of this
      disease. We report a rare case of severe PLCH in a young non smoking female with
      a short history who progressed rapidly to respiratory failure and died. 

PMID- 25857565
TI  - Multifocal tuberculous osteomyelitis: A rare presentation.
AB  - A 29 year old lady presented with vague right lower quadrant abdomen and thigh
      pain for the past 4 years. X-ray pelvis with both hips was remarkably normal, and
      MRI was suggestive of osteomyelitis in right ilium and proximal femur. Biopsy
      confirmed the lesion as tubercular. Isolated bone involvement by tuberculosis
      without a joint or pulmonary involvement is extremely rare in immunocompetent
      patients and has not been reported in literature so for. Tuberculosis should be
      suspected in patients presenting with multiple bone lesions, especially in
      endemic areas. Prompt surgical drainage and ATT forms the mainstay of treatment. 

PMID- 25857567
TI  - Cavitating lung disease due to concomitant drug resistant tuberculosis and
      invasive pulmonary Aspergillosis in a post-partum patient: A case report.
AB  - Many disorders can present as cavitating lesions in the lung. In this case
      report, a case of mixed infection with drug resistant tuberculosis and invasive
      pulmonary aspergillosis in a post-partum patient has been presented. 

PMID- 25857568
TI  - Response to Dr Daley's article: Do not ignore the private sector.

PMID- 25857569
TI  - The evolution of mobile apps for asthma: an updated systematic assessment of
      content and tools.
AB  - BACKGROUND: Interest in mobile apps that support long-term conditions such as
      asthma is matched by recognition of the importance of the quality and safety of
      apps intended for patient use. We assessed how changes over a 2-year period
      affected the clinical suitability of apps providing self-management information
      and tools for people with asthma by updating a review first performed in 2011.
      METHODS: Systematic content assessment of all apps for iOS and Android examining
      the comprehensiveness of asthma information, consistency with the evidence base
      for asthma self-management and adherence to best practice principles for
      trustworthy content, comparing the quality of apps available in 2011 to those
      released since. RESULTS: Between 2011 and 2013, numbers of asthma apps more than
      doubled from 93 to 191, despite withdrawal of 25% (n = 23/93) of existing apps.
      Newer apps were no more likely than those available in 2011 to include
      comprehensive information, such as the use of action plans, or offer guidance
      consistent with evidence; 13% (n = 19/147) of all apps, and 39% (n = 9/23) of
      those intended to manage acute asthma, recommended self-care procedures
      unsupported by evidence. Despite increases in the numbers of apps targeting
      specific skills, such as acute asthma management (n = 12 to 23) and inhaler
      technique (from n = 2 to 12), the proportion consistent with guidelines (17%, n =
      4/23) and inhaler instructions (25%, n = 3/12), respectively, was low, and most
      apps provided only either basic information about asthma (50%, n = 75/147) or
      simple diary functions (24%, n = 36/147). CONCLUSIONS: In addition to persisting
      questions about clinical quality and safety, dynamic aspects of app turnover and
      feature evolution affect the suitability of asthma apps for use in routine care.
      The findings underline the need for coordinated quality assurance processes that
      can adapt to changing clinical and information governance-related risks, ensure
      compliance with the evidence base and reflect local variations in clinical
      practice. It is unclear if substantial clinical benefits can be realized from a
      landscape dominated by low quality generic information apps and tools that do not
      adhere to accepted medical practice.

PMID- 25857570
TI  - Inhibition to DRP1 translocation can mitigate p38 MAPK-signaling pathway
      activation in GMC induced by hyperglycemia.
AB  - Diabetic nephropathy (DN) is a serious complication of diabetes with a poorly
      defined etiology and limited treatment options. Early intervention is a key to
      preventing the progression of DN. Dynamin-related protein 1 (DRP1) regulates
      mitochondrial morphology by promoting its fission and is involved in the
      pathogenesis of numerous diseases. Furthermore, DRP1 is also closely associated
      with the development of diabetes, but its functional role in DN remains unknown.
      This study investigated the effect of DRP1 on early stage of DN. DRP1 expression
      has increased significantly in glomerular mesangial cell (GMC), which is
      cultivated in high glucose (HG). Ultra-microstructural changes of nephrons,
      expression of collagen IV and phosph-p38, ROS production, and mitochondrial
      function were evaluated and, at the same time, were compared with glomerular
      mesangial cell (GMC) cultured in normal-glucose (NG), mannitol, and a medium with
      mitochondrial division inhibitor 1 (Midivi-1). Endogenous DRP1 expression
      increased in DN. Compared to the control groups ofNG and mannitol, overexpression
      of DRP1 destroyed pathological changes typical of the GMC, like accumulation of
      extracellular matrix, and an increase in mitochondria division. In addition,
      Overexpression of DRP1 promoted the activation of p38, the accumulation of ROS,
      mitochondrial dysfunction, and the synthesis of collagen IV, and all these
      changes are suppressed by Midivi-1. This study demonstrates that DRP1
      overexpression can accelerate pathological changes in the GMC cultured in HG.
      Further studies are needed to clarify the underlying mechanism of this
      destructive function. 

PMID- 25857571
TI  - To the point: teaching the obstetrics and gynecology medical student in the
      operating room.
AB  - This article, from the "To the Point" series that is prepared by the Association
      of Professors of Gynecology and Obstetrics Undergraduate Medical Education
      Committee, is a review of considerations for teaching the medical student in the
      operating room during the obstetrics/gynecology clerkship. The importance of the
      medical student operating room experience and barriers to learning in the
      operating room are discussed. Specific considerations for the improvement of
      medical student learning and operating room experience, which include the
      development of operating room objectives and specific curricula, an increasing
      awareness regarding role modeling, and faculty development, are reviewed. 

PMID- 25857573
TI  - Morbidity, mortality and survival after surgery for lung cancer.

PMID- 25857575
TI  - Set our talented professionals free.

PMID- 25857572
TI  - MAGNETIC RESONANCE IMAGING FEATURES AND OUTCOME FOR SOLITARY CENTRAL NERVOUS
      SYSTEM COCCIDIOIDES GRANULOMAS IN 11 DOGS AND CATS.
AB  - Little published information is available to guide therapy for canine and feline
      patients with Coccidioides infections involving the central nervous system (CNS).
      The purpose of this cross-sectional retrospective study was to describe magnetic
      resonance imaging (MRI) features and outcome for a group of dogs and cats with
      solitary CNS Coccidiodes granulomas. Nine canine and two feline cases met
      inclusion criteria; four diagnosed and treated with surgery and fluconazole and
      seven diagnosed by serology or cytology and treated medically. Three cases had
      left Coccidioides endemic areas long before developing neurological disease. The
      MRI lesions shared many features with neoplastic masses. The extra-axial
      granulomas often had a lack of a distinct border between the mass and neural
      parenchyma. Four cases were extra-axial and seven were intra-axial, but
      distinguishing between extra-axial and intra-axial locations was sometimes
      challenging. The surgical cases had good outcomes and histology allowed
      definitive diagnosis. Medically managed patients also had generally good
      outcomes, with resolution of clinical signs in most cases. Findings indicated
      that distinction between neoplasia and focal Coccidioides granulomas based on MRI
      features is likely to be imprecise. Demonstration of the organism by cytology or
      histology is required for definitive diagnosis. The role of surgery for improving
      the outcome of brain or spinal coccidioidomycosis granulomas warrants further
      study. 

PMID- 25857574
TI  - A quantitative proteomic analysis of cellular responses to high glucose media in
      Chinese hamster ovary cells.
AB  - A goal in recombinant protein production using Chinese hamster ovary (CHO) cells
      is to achieve both high specific productivity and high cell density. Addition of
      glucose to the culture media is necessary to maintain both cell growth and
      viability. We varied the glucose concentration in the media from 5 to 16 g/L and
      found that although specific productivity of CHO-DG44 cells increased with the
      glucose level, the integrated viable cell density decreased. To examine the
      biological basis of these results, we conducted a discovery proteomic study of
      CHO-DG44 cells grown under batch conditions in normal (5 g/L) or high (15 g/L)
      glucose over 3, 6, and 9 days. Approximately 5,000 proteins were confidently
      identified against an mRNA-based CHO-DG44 specific proteome database, with 2,800
      proteins quantified with at least two peptides. A self-organizing map algorithm
      was used to deconvolute temporal expression profiles of quantitated proteins.
      Functional analysis of altered proteins suggested that differences in growth
      between the two glucose levels resulted from changes in crosstalk between glucose
      metabolism, recombinant protein expression, and cell death, providing an overall
      picture of the responses to high glucose environment. The high glucose
      environment may enhance recombinant dihydrofolate reductase in CHO cells by up
      regulating NCK1 and down-regulating PRKRA, and may lower integrated viable cell
      density by activating mitochondrial- and endoplasmic reticulum-mediated cell
      death pathways by up-regulating HtrA2 and calpains. These proteins are suggested
      as potential targets for bioengineering to enhance recombinant protein
      production.

PMID- 25857576
TI  - Inference of posterior inclusion probability of QTLs in Bayesian shrinkage
      analysis.
AB  - Bayesian shrinkage analysis estimates all QTLs effects simultaneously, which
      shrinks the effect of "insignificant" QTLs close to zero so that it does not need
      special model selection. Bayesian shrinkage estimation usually has an excellent
      performance on multiple QTLs mapping, but it could not give a probabilistic
      explanation of how often a QTLs is included in the model, also called posterior
      inclusion probability, which is important to assess the importance of a QTL. In
      this research, two methods, FitMix and SimMix, are proposed to approximate the
      posterior probabilities. Under the assumption of mixture distribution of the
      estimated QTL effect, FitMix and SimMix mathematically and intuitively fit
      mixture distribution, respectively. The simulation results showed that both
      methods gave very reasonable estimates for posterior probabilities. We also
      applied the two methods to map QTLs for the North American Barley Genome Mapping
      Project data. 

PMID- 25857577
TI  - Editorial.
AB  - Effective communication sometimes requires a common language. This is
      particularly true in science, where communication among health professionals and
      scientists across national boundaries has become critical because of the rapidity
      with which new knowledge is acquired. In the modern era, where multinationalism
      in key medical and scientific discoveries is increasingly common, the language is
      undoubtedly English. In fact, more than three-quarters of scientific papers today
      are published in English. 

PMID- 25857578
TI  - Functional respiratory assessment in interstitial lung disease.
AB  - Interstitial lung diseases are a heterogeneous group of disorders that affect, to
      a greater or lesser degree, the alveolus, peripheral airway, and septal
      interstitium. Functional assessment in patients suspected of having an
      interstitial lung disease has implications for diagnosis and makes it possible to
      objectively analyze both response to treatment and prognosis. Recently the
      clinical value of lung-diffusing capacity and the six-minute walking test has
      been confirmed, and these are now important additions to the traditional
      assessment of lung function that is based on spirometry. Here we review the state
      of-the-art methods for the assessment of patients with interstitial lung disease.

PMID- 25857579
TI  - Pharmacoperones: targeting therapeutics toward diseases caused by protein
      misfolding.
AB  - Pharmacoperones are hydrophobic molecule drugs that enter cells and serve as a
      molecular framework to cause misfolded mutant proteins to fold properly and adopt
      a stable conformation compatible with proper intracellular trafficking.
      Pharmacoperones have successfully been used experimentally to rescue function of
      some misfolded proteins (enzymes, receptors, channels) that lead to disease.
      Identification of pharmacoperones by high-throughput screens of drug libraries
      will likely provide new molecules that may be potentially useful to treat
      diseases caused by protein misfolding. 

PMID- 25857580
TI  - Association between high serum estradiol levels and delirium among hospitalized
      elderly women.
AB  - BACKGROUND: Delirium is a common and serious disorder among hospitalized elderly
      individuals. We investigated the association between serum estradiol levels and
      incident delirium. METHODS: Longitudinal study of 141 women >= 70 years old
      admitted to a tertiary care hospital in Mexico City. All participants underwent a
      comprehensive geriatric assessment. Blood samples for cortisol and estradiol
      determination were obtained at hospital admission. Incident delirium was
      investigated until participants were discharged. Multivariate models were run to
      test the independent association between estradiol levels and incident delirium.
      RESULTS: Twenty-three (16.3%) participants developed delirium. Estradiol levels
      were higher among women with incident delirium compared with non-affected women.
      Multivariate logistic regression analysis showed that serum estradiol levels were
      associated with incident delirium even after adjusting for multiple confounding
      covariates, including cortisol levels (OR: 1.93; 95% CI: 1.28-2.92). CONCLUSIONS:
      Elderly women with high serum estradiol levels at hospital admission had an
      increased risk for incident delirium. Serum estradiol may be a biomarker for
      increased risk of delirium.

PMID- 25857581
TI  - Retinal thickness after focal photocoagulation for diabetic macular edema with
      and without temporal perifoveal thickening.
AB  - BACKGROUND: Visual improvement after focal photocoagulation in diabetic macular
      edema is more common in eyes without temporal perifoveal thickening. This feature
      is related to a lower macular volume before treatment; the higher proportion of
      visual improvement could be associated with a shorter need of volume reduction.
      OBJECTIVE: To compare macular volume before and after focal photocoagulation in
      eyes with diabetic macular edema, with and without temporal perifoveal
      thickening. METHODS: Non-experimental, retrospective, longitudinal, comparative
      study in diabetics with macular edema treated with focal photocoagulation.
      Macular volume measured with optical coherence tomography, and best corrected
      visual acuity were compared between eyes with (group 1) and without temporal
      perifoveal thickening (group 2, independent samples Student's t test). The
      comparison was also performed after stratifying the groups by baseline visual
      acuity. RESULTS: One hundred and twenty eyes, 65 eyes from group 1 (54.2%) and 55
      from group 2 (45.8%). Mean volume before and after treatment and mean absolute
      and percentage changes were lower in group 2 (p < 0.001) regardless of visual
      acuity. Macular volume decreased significantly in eyes of group 1; only eyes in
      group 2 with visual acuity < 0.5 before treatment increased their visual function
      (p < 0.001). CONCLUSIONS: Eyes without temporal perifoveal thickening had visual
      improvement, although their volume did not change statistically. The significant
      volume reduction in eyes with temporal perifoveal thickening was not associated
      to visual improvement. The anatomical change was not enough to explain the
      functional improvement.

PMID- 25857582
TI  - Sarcoidosis: a single hospital-based study in a 24-year period.
AB  - BACKGROUND: Clinical presentation of sarcoidosis varies according to race and
      geographical area. We describe the clinical spectrum and outcome of sarcoidosis
      in Mexican patients compared with other populations. METHODS: We reviewed the
      medical charts of 21 patients with sarcoidosis seen at a referral hospital in
      1989-2012; organ involvement was assessed using the ACCESS instrument. We
      compared our results with the ACCESS and Latin American studies. We used
      descriptive statistics and reported odd ratios with 95% CI. RESULTS AND
      CONCLUSION: Fifty-two percent were women; median age was 31 years; median time to
      diagnosis, 5.5 months. Frequency of organ involvement was: constitutional
      symptoms 62%, lungs 66.6%, skin 42.8%, bone marrow 23.4%, lymph node 19%, liver
      19%, and eye 19%. After one year of follow-up, 47.5% of patients were
      asymptomatic without treatment, 38% asymptomatic on treatment, and 14.2%
      symptomatic on treatment. In our patients, pulmonary involvement was lower (66.6
      vs. 94.9%; p = 0.001) and cutaneous (42.8 vs. 15.8%; p = 0.003) and bone marrow
      (23.4 vs. 4.7%; p = 0.001) were higher than in the ACCESS cohort. Data regarding
      Latin American populations was scarce. The clinical spectrum of sarcoidosis in
      our population differed from other studies, with a higher frequency of cutaneous
      sarcoidosis and less pulmonary involvement.

PMID- 25857583
TI  - Morbidity and mortality following cytoreductive surgery with hyperthermic
      intraperitoneal chemotherapy at a tertiary care center: initial experience.
AB  - BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy
      increases progression-free and overall survival in patients with peritoneal
      carcinomatosis of appendicular or colorectal origin. The morbidity associated
      with this procedure is significant (30-52%). This modality is also routinely used
      in other peritoneal diseases with improvement of outcome. The aim of this study
      was to analyze the morbidity and mortality associated with this procedure.
      MATERIAL & METHODS: Thirteen patients had cytoreductive surgery and hyperthermic
      intraperitoneal chemotherapy in a period from May 2011 to March 2013 and were
      followed up prospectively. Demographic, pathologic, and surgical variables were
      recorded. The Clavien-Dindo classification was used to assess surgical
      complications. The main outcome variable was 30-day morbidity and mortality.
      Descriptive statics were used. RESULTS: The mean patient age was 52.4 +/- 11.1
      years. The most common diagnosis was epithelial ovarian cancer (46.2%). Most
      patients had an adequate preoperative functional status (77% with ECOG 0). Mean
      hospital stay was 13.5 +/- 11.2 days and 2.7 +/- 4.2 days in the intensive care
      unit. Major morbidity (Clavien-Dindo III or IV) observed in this series was 23%,
      with 0% mortality. CONCLUSION: Cytoreductive surgery and hyperthermic
      intraperitoneal chemotherapy is a feasible option with acceptable morbidity and
      mortality for selected patients with peritoneal carcinomatosis in Mexico.

PMID- 25857584
TI  - Oxidative stress in patients with rheumatoid arthritis.
AB  - BACKGROUND: Rheumatoid arthritis is an autoimmune disease of unknown etiology,
      characterized by articular inflammation. Oxidative damage induced by reactive
      oxygen species has been related to the pathophysiology of rheumatoid arthritis in
      several studies, although results have been inconsistent and contradictory.
      OBJECTIVE: To determine oxidative stress markers in patients with rheumatoid
      arthritis. METHODS: Descriptive cross-sectional study in rheumatoid arthritis
      patients and healthy controls. In peripheral blood samples from all study
      subjects, lipid peroxide (thiobarbituric acid reactive substances) and protein
      carbonyl levels were quantified as oxidative damage markers; superoxide dismutase
      and glutathione peroxidase activities, glutathione concentration, and the reduced
      glutathione/oxidized glutathione ratio were analyzed as antioxidant defense
      indicators. Mann-Whitney U tests were run. Statistical significance (a) was
      0.05%. RESULTS: We included 29 rheumatoid arthritis patients, 10 with active
      disease, and 41 healthy controls. Age was higher in the rheumatoid arthritis
      group; there were no differences in female:male ratio between groups. Oxidative
      damage was higher in rheumatoid arthritis patients; however, there was no
      difference between patients with active or inactive rheumatoid arthritis.
      Antioxidant enzyme activities, glutathione concentration, and reduced
      glutathione/oxidized glutathione ratio were higher in rheumatoid arthritis
      patients than in controls. CONCLUSIONS: Antioxidant levels were higher in
      rheumatoid arthritis patients than in healthy controls; however, they were
      insufficient to prevent oxidative damage. This suggests an active oxidative
      process in rheumatoid arthritis patients.

PMID- 25857585
TI  - Eating disorders associated risk factors: trends from 2007 to 2010.
AB  - OBJECTIVE: The purpose of this study was to determine the trends on risk factors
      associated to eating disorders in bachelor students from an urban setting in
      Hidalgo in the period 2007-2010. MATERIAL AND METHODS: Students were censored
      both in 2007 and in 2010, and registered as 455 (50.5% female, 49.5% male)
      students in 2007 and 434 (49.8% female, 50.2% male) in 2010, aged 15-19 years in
      both cases. Three questionnaires were used to assess sociocultural factors,
      disordered eating behaviors, and body aesthetic thin-ideal internalization. Body
      dissatisfaction was measured with nine body figure analogic. To assess body mass
      index, each subject was weighed and height measured. Comparisons by year and
      gender were obtained. RESULTS: Body shape distress increased from 20.8% in 2007
      to 21.7% in 2010; disordered eating behaviors trends increased from 2007 to 2010
      both in females and males, but were statistically significant only in males. The
      percentage of subjects with body dissatisfaction in the sense to be thinner was
      the same in both years (39.8%). The risk analysis showed an increase in those
      with disordered eating, in thin-ideal internalization, advertising influence, and
      body shape distress, mainly in women. CONCLUSIONS: These findings must be
      considered in the design of preventive programs and early case detection in
      adolescents from Hidalgo.

PMID- 25857586
TI  - Malignant middle cerebral artery infarction: a clinical study of 32 patients.
AB  - BACKGROUND AND OBJECTIVE: Malignant middle cerebral artery infarction is a
      devastating type of ischemic stroke whose clinical predictors remain scarcely
      known. The present study aims to improve the knowledge about the prognosis
      factors through an analysis of a malignant middle cerebral artery infarction
      sample of patients from our stroke registry. MATERIAL AND METHODS: From a total
      of 1,396 patients with ischemic stroke in the middle cerebral artery included in
      the "Sagrat Cor Hospital of Barcelona Stroke Registry", we identified 32 patients
      with malignant middle cerebral artery infarction (2.3%). Demographic, anamnestic,
      clinical, and outcome variables in this subgroup of patients were compared with
      those of the middle cerebral artery. The independent predictive value of each
      variable on the development of malignant middle cerebral artery infarction was
      assessed with a logistic regression analysis. RESULTS: The mean age was 74.7 (SD,
      11.4) years and 50% were males. In-hospital death was observed in eight patients
      (25%) and early bad prognosis (in-hospital death or severe residual focality at
      discharge) was present in 16 patients (50%). Decreased consciousness (OR: 4.17;
      95% CI: 2.02-8.61), presence of nausea or vomiting (OR: 3.65; 95% CI: 1.40-8.49),
      and heavy smoking (> 20 cigarettes/day; OR: 2.62; 95% CI: 1.03-6.64) appeared to
      be independent prognostic factors for malignant middle cerebral artery infarction
      in the multivariate analysis. CONCLUSIONS: Malignant middle cerebral artery
      infarction is an infrequent clinical condition associated with poor prognosis and
      high mortality rate. In our sample, decreased consciousness, nausea or vomiting,
      and heavy smoking are the main clinical factors associated.

PMID- 25857587
TI  - Anti-osteoporotic activity of puerarin 6"-O-xyloside on ovariectomized mice and
      its potential mechanism.
AB  - CONTEXT: Osteoporosis is one of the most common bone diseases, and radix of
      Pueraria lobata (Willd.) Ohwi possesses an obvious therapeutical effect on
      postmenopausal osteoporosis. OBJECTIVE: This study investigates the anti
      osteoporotic activity of the puerarin 6"-O-xyloside (PXY) on ovariectomized mice
      and its related mechanism. MATERIALS AND METHODS: Osteoporotic mice model was
      established by ovariectomy (OVX). A total of 50 mice were divided into five
      groups (n = 10): sham, OVX group, PXY treatment groups (20, 40, and 60 mg/kg/d,
      i.p.). After 12 weeks' treatment, body weights were recorded. Then, mice were
      sacrificed, and serum samples were collected to determine the blood calcium,
      blood phosphorus, alkaline phosphatase (ALP), and osteoprotegerin (OPG)
      concentrations and uterine index was assayed. The thigh-bones of mice were
      collected to evaluate histopathological changes. In the in vitro experiment, the
      effect of PXY on osteoblasts' proliferation was evaluated and western blotting
      was performed to determine expressions of OPG and the receptor activators of NF
      kappaB ligand (RANKL), as well as the ratio of OPG/RANKL. RESULTS: PXY (40 and 60
      mg/kg/d, i.p.) obviously decreased body weights and increased uterine index of
      OVX (p < 0.05), and improved osteoporotic syndromes of OVX mice; PXY also
      significantly increased the concentrations of blood calcium, blood phosphorus,
      ALP, and OPG of OVX mice (p < 0.05); moreover, PXY obviously up-regulated the
      ratio of OPG/RANKL (p < 0.05). CONCLUSION: Our results demonstrated that the
      puerarin 6"-O-xyloside possesses significant anti-osteoporotic activity on
      ovariectomy mice.

PMID- 25857589
TI  - Radiation-mode optical microscopy on the growth of graphene.
AB  - Chemical vapour deposition (CVD) growth of graphene has attracted much attention,
      aiming at the mass production of large-area and high-quality specimens. To
      optimize the growth condition, CVD grown graphene is conventionally characterized
      after synthesis. Real-time observation during graphene growth enables us to
      understand the growth mechanism and control the growth more easily. Here we
      report the optical microscope observation of the CVD growth of graphene in real
      time by focusing the radiation emitted from the growing graphene, which we call
      'radiation-mode optical microscopy'. We observe the growth and shrinkage of
      graphene in response to the switching on and off of the methane supply. Analysis
      of the growth feature reveals that the attachment and detachment of carbon
      precursors are the rate-determining factor in the CVD growth of graphene. We
      expect radiation-mode optical microscopy to be applicable to the other crystal
      growth at high temperatures in various atmospheres. 

PMID- 25857588
TI  - Idiopathic spinal cord herniation: an imaging diagnosis with a significant delay.
AB  - BACKGROUND CONTEXT: Idiopathic spinal cord herniation (ISCH) is an
      underrecognized entity that is often underappreciated by the neurosurgery and
      neuroradiologic communities. This leads to delayed diagnosis, multiple imaging
      studies, other diagnostic tests, inappropriate surgeries, and repeat office
      visits. PURPOSE: To evaluate common associations between ISCH and patient
      demographics/clinical presentation and to analyze the potential for delayed
      diagnosis. PATIENT SAMPLE: Patient sample included those diagnosed with ISCH on
      imaging at our institution from June 20, 2005 to December 3, 2012. OUTCOME
      MEASURES: These were based on the patient improvement/stability/decline based on
      the patients' most recent clinic/office visit when compared with initial
      presentation. METHODS: A retrospective search of radiology reports was performed
      using Illuminate software from June 20, 2005 to December 3, 2012, using the
      search term "idiopathic spinal cord herniation." Clinical data were reviewed
      including patient's age, sex, presenting clinical symptoms, number and type of
      imaging studies performed as part of the workup, other diagnostic tests, pain
      procedures, surgeries, and time between original presentation and diagnosis of
      ISCH on imaging. RESULTS: A total of 55 patients had the search term "idiopathic
      spinal cord herniation" included in their radiology report, of which 37 patients
      were found to meet the imaging and clinical diagnosis of ISCH. The median time
      from presentation to imaging diagnosis was 20 months in patients younger than 60
      years and 5 months in those 60 years or older (p=.02). Of the 37 patients
      evaluated, 27 (73%) had no change in symptoms, 5 patients (14%) experienced
      worsening of symptoms, and 5 (14%) experienced symptom improvement from original
      presentation to most recent office visit. Among all patients evaluated, three
      underwent repair of the ventral dural defect in ISCH, resulting in clinical
      improvement. There was a median of nine outpatient office visits, three magnetic
      resonance images (MRIs), and one electromyography (EMG) per patient presenting
      with ISCH. The most frequent complaints were neck/upper back pain in 70%,
      upper/lower extremity numbness/paresthesias/weakness in 49%, hyperreflexia in
      22%, and burning chest pain in 22%. CONCLUSIONS: Prolonged time to diagnosis and
      subsequent treatment of ISCH protracts patient symptoms and is associated with
      redundant diagnostic tests and patient visits. Earlier use of MRI in younger
      patients (younger than 60 years) may be warranted in those with a clinical
      presentation suggestive of Brown-Sequard symptomatology. Increasing recognition
      of ISCH in imaging and surgical communities would lead to improved patient care.

PMID- 25857590
TI  - Percutaneous Ultrasonic Fasciotomy for Refractory Plantar Fasciopathy After
      Failure of a Partial Endoscopic Release Procedure.
AB  - Plantar fasciopathy is a painful, degenerative condition of the plantar fascia
      that affects 2 million people annually and has an estimated 10% lifetime
      prevalence. When both nonoperative and operative management fails, patients have
      limited therapeutic options. We present a case of an active 47-year-old male
      runner who was successfully treated with songraphically guided percutaneous
      ultrasonic fasciotomy after undergoing a prolonged course of nonoperative
      management and an endoscopic plantar fascia release procedure. Percutaneous
      ultrasonic fasciotomy may be considered in patients with chronic, refractory
      plantar fasciopathy, including those for whom a prior operative release procedure
      has failed.

PMID- 25857591
TI  - Successful Rehabilitation of a Young Adult With Total Hip Arthroplasty a Decade
      After a Girdlestone Procedure: A Case Presentation.
AB  - This is a case presentation of a female patient who underwent a Girdlestone
      arthroplasty at age 10 years and a total hip arthroplasty at age 21. Despite
      early postoperative rehabilitation, the patient experienced increasing pain,
      progressive gait deviations, and functional limitations during the year after
      surgery. This course of care was initiated 1 year after surgery and focused on
      motor retraining to address pain and gait deviations. This case demonstrates that
      positive outcomes can be achieved after longstanding musculoskeletal dysfunction
      is corrected, but that prolonged rehabilitation may be necessary to produce
      changes in movement patterns at both the local (joint and muscle) and central
      (cortical) levels. Correction of both the structural problem and the learned
      movement patterns is necessary for a successful outcome. 

PMID- 25857592
TI  - Atypical Coxa Saltans Due to Partial Proximal Hamstring Avulsion: A Case
      Presentation Highlighting the Role for Dynamic Sonography.
AB  - Painful hip snapping can present as a rare sequela of proximal hamstring injury.
      We present a case of painful snapping of the conjoint tendon of the
      semitendinosus and biceps femoris over the ischial tuberosity in the setting of a
      partial proximal hamstring disruption. Dynamic ultrasonography identified the
      source of snapping and a persistent attachment of the conjoint tendon to the
      sacrotuberous ligament, which prevented retraction and allowed subluxation of the
      tendons across the ischial tuberosity. Following surgical transection of the
      persistent sacrotuberous ligament attachment to the conjoint tendon and tendon
      reattachment, the patient's symptoms resolved with full return of function. 

PMID- 25857593
TI  - Sonographic Appearance of the Extensor Carpi Radialis Intermedius Tendon.

PMID- 25857594
TI  - Randomized, Multicenter Clinical Study of Tratinterol Hydrochloride Tablets for
      the Treatment of Bronchial Asthma.
AB  - PURPOSE: The aim of this study was to determine the efficacy and safety profile
      of tratinterol hydrochloride tablets in the treatment of bronchial asthma.
      METHODS: This multicenter, randomized, double-blind clinical research study was
      completed at 6 centers in the People's Republic of China from March 2009 to June
      2010, and a randomized trial of procaterol hydrochloride tablets produced by
      Otsuka Pharmaceutical Co Ltd was conducted. The study was approved by the Medical
      Ethics Committee of the First Hospital of China Medical University. The clinical
      trial registration number is 2007L04263. FINDINGS: A total of 223 patients were
      selected for this study, with 112 patients in the treatment group and 111 in the
      control group. The lung function of the 2 groups after treatment significantly
      increased in all (P < 0.05); however, there was no significant difference in the
      changes between the 2 groups (P > 0.05). The occurrence of related adverse events
      at varying degrees in the control group was higher than in the treatment group.
      IMPLICATIONS: It is safe and effective to use tratinterol hydrochloride tablets
      to treat bronchial asthma.

PMID- 25857595
TI  - Association Between Colchicine and Risk of Diabetes Among the Veterans Affairs
      Population With Gout.
AB  - PURPOSE: This study aimed to determine the association between colchicine use and
      the incidence of diabetes in a cohort of patients with gout. METHODS: This is a
      retrospective study of 27,876 adults with gout identified via the Veterans
      Integrated Services Network 16 data warehouse. Patients had up to 11 years of
      follow-up (January 1999 through December 2010). The final study sample consisted
      of 1046 pairs of 1:1 propensity score-matched patients from the colchicine
      treated and control cohorts. Time to first diabetes development since the first
      gout diagnosis was modeled. RESULTS: After the propensity score matching, the 12
      month baseline variables (eg, age, sex, race, index year, body mass index, serum
      uric acid, antigout drug use, and health care use) were comparable between the
      matched cohorts (P > 0.05 for all). Among the 1046 matched pairs, 234 patients
      who had taken colchicine and 224 patients who had never taken colchicine
      developed diabetes; the incidence rates were 38.95 and 39.02 per 1000 patient
      years, respectively. In Poisson and Cox proportional hazards regression, the risk
      of incident diabetes was reduced with increased duration of colchicine use, but
      the difference was not statistically significant (P > 0.05). In a time-varying
      Cox proportional hazards model, the hazard ratio for incident diabetes among
      patients who had taken colchicine was 0.877 (95% CI, 0.662-1.163; P = 0.362)
      compared with those who had not taken colchicine. CONCLUSION: This study suggests
      a possible duration- or dose-related association between colchicine use and
      reduced risk of diabetes in adults with gout even though the risk reduction was
      not significant. Further studies are needed to confirm findings from this study.

PMID- 25857596
TI  - Changes in phosphorylation of adenosine phosphate and redox state of nicotinamide
      adenine dinucleotide (phosphate) in Geobacter sulfurreducens in response to
      electron acceptor and anode potential variation.
AB  - Geobacter sulfurreducens is one of the dominant bacterial species found in
      biofilms growing on anodes in bioelectrochemical systems. The intracellular
      concentrations of reduced and oxidized forms of nicotinamide-adenine dinucleotide
      (NADH and NAD(+), respectively) and nicotinamide-adenine dinucleotide phosphate
      (NADPH and NADP(+), respectively) as well as adenosine triphosphate (ATP),
      adenosine diphosphate (ADP), and adenosine monophosphate (AMP) were measured in
      G. sulfurreducens using fumarate, Fe(III)-citrate, or anodes poised at different
      potentials (110, 10, -90, and -190 mV (vs. SHE)) as the electron acceptor. The
      ratios of CNADH/CNAD+ (0.088+/-0.022) and CNADPH/CNADP+ (0.268+/-0.098) were
      similar under all anode potentials tested and with Fe(III)-citrate (reduced
      extracellularly). Both ratios significantly increased with fumarate as the
      electron acceptor (0.331+/-0.094 for NAD and 1.96+/-0.37 for NADP). The adenylate
      energy charge (the fraction of phosphorylation in intracellular adenosine
      phosphates) was maintained near 0.47 under almost all conditions. Anode-growing
      biofilms demonstrated a significantly higher molar ratio of ATP/ADP relative to
      suspended cultures grown on fumarate or Fe(III)-citrate. These results provide
      evidence that the cellular location of reduction and not the redox potential of
      the electron acceptor controls the intracellular redox potential in G.
      sulfurreducens and that biofilm growth alters adenylate phosphorylation.

PMID- 25857597
TI  - A randomised controlled trial of radial artery cannulation guided by Doppler vs.
      palpation vs. ultrasound.
AB  - We randomly allocated 749 participants to radial artery cannulation by
      anaesthetic trainees, guided by Doppler (244), palpation (256) or ultrasound
      (249). Ultrasound increased the rate of cannulation at the first attempt by 14%
      (95% CI 5-22%), from 39% with Doppler or palpation, p = 0.002 for both. There
      were no differences in the rates of cannulation 5 min after the procedure
      started: 147/244 (60%) with Doppler; 160/256 (63%) with palpation; and 171/249
      (69%) with ultrasound, p = 0.13. 

PMID- 25857598
TI  - Construction of a cell-surface display system based on the N-terminal domain of
      ice nucleation protein and its application in identification of mycoplasma
      adhesion proteins.
AB  - AIMS: To construct and demonstrate a surface display system that could be used to
      identify mycoplasma adhesion proteins. METHODS AND RESULTS: Using the N-terminal
      domain of InaZ (InaZN) as the anchoring motif and the enhanced green fluorescent
      protein (EGFP) as the reporter, the surface display system pET-InaZN-EGFP was
      constructed. Then, the mgc2 gene which encodes an adhesin and the holB gene which
      encodes DNA polymerase III subunit delta' (nonadhesin, negative control) of
      Mycoplasma gallisepticum were cloned into the pET-InaZN-EGFP respectively. The
      fusion proteins were expressed in Escherichia coli BL21 (DE3). The distribution
      of the fusion proteins in E. coli cells was determined using SDS-PAGE followed by
      Western blotting, based on cell fractionation. Escherichia coli cell surface
      display of the fusion protein was confirmed by immunofluorescence microscopy. The
      results indicated that the fusion proteins were not only anchored to the outer
      membrane fraction but also were successfully displayed on the surface of E. coli
      cells. Adhesion analysis of E. coli harbouring InaZN-EGFP-mgc2 to host cells
      showed that the MGC2-positive E. coli cells can effectively adhere to the
      surfaces of DF-1 cells. CONCLUSIONS: A surface display system using the InaZN as
      the anchoring motif and EGFP as the reporter was developed to identify putative
      adhesins of mycoplasma. Results indicated that adhesion by the cytadhesin-like
      protein MGC2 of mycoplasma can be reproduced using this surface display system.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first construction of surface
      display system which could be used to identify the adhesion proteins of
      mycoplasma. The method developed in this study can even be used to select and
      identify the adhesion proteins of other pathogens.

PMID- 25857599
TI  - Electrolyte ion adsorption and charge blocking effect at the hematite/aqueous
      solution interface: an electrochemical impedance study using multivariate data
      analysis.
AB  - A model-free multivariate analysis using singular value decomposition is employed
      to refine an equivalent electrical circuit model in order to probe the
      electrochemical properties of the hematite/water interface in dilute NaCl and
      NH4Cl solutions using electrochemical impedance spectroscopy. The result shows
      that the surface protonation is directly related to the mobility and trapping of
      charge carriers at the mineral surface. Moreover, the point of zero charge can be
      found at pH where the charge transfer resistance is the highest, in addition to
      the minimum double layer capacitance. The inner-sphere interaction of the NH4(+)
      ion with the surface is indicated by an increase of capacitance for charge
      carrier trapping from the protonated surface as well as lower double layer
      capacitance and open circuit potential. It is clear that the intrinsic
      electrochemical activity of hematite depends on the degree of surface
      (de)protonation and other inner-sphere adsorption, as these processes affect the
      charge carrier density in the surface state. This work also highlights an
      important synergistic effect of the two spectral analyses that enables EIS to be
      utilized in an in-depth investigation of mineral/water interfaces. 

PMID- 25857600
TI  - Accuracy of a predictive bioelectrical impedance analysis equation for estimating
      appendicular skeletal muscle mass in a non-Caucasian sample of older people.
AB  - OBJECTIVE: To design and validate a predictive BIA equation to estimate ASM in a
      sample of non-Caucasian older people and to explore the accuracy of two previous
      single-frequency BIA published equations. METHOD: This is a cross-sectional study
      in 213 physically-independent and apparently healthy older men and women subjects
      from a central region of Mexico. Dual-energy X-ray absorptiometry, anthropometry,
      resistance, reactance, and other independent predictive variables were assessed.
      The total sample was randomized and split into two sub-samples: one group for the
      development of the predictive single-frequency BIA equation and the other for its
      validation. The equation was derived by step-wise regression, the goodness of fit
      was assessed by the highest determination coefficient (R(2)) and precision by the
      lowest root mean square error. In the validation sample, the accuracy of the new
      and the published BIA equations was tested by pure error. In addition, Bland and
      Altman analysis tested the bias. RESULTS: The selected model had a R(2) of 0.91
      and a RMSE of 1.01 kg and fulfilled every regression assumption. The predictive
      variables included were: Ht(2)/R, sex, and body weight. The new BIA equation
      showed a PE close to RMSE of the estimate with no significant bias. The published
      BIA equations proved to be inaccurate and had significant bias. CONCLUSIONS: This
      new single-frequency BIA-derived equation was precise, accurate and free of bias.
      Published BIA equations to estimate ASM should not be used indistinctly in other
      ethnic groups without validation.

PMID- 25857601
TI  - Continuous blood pressure measurement using the pulse transit time: Comparison to
      intra-arterial measurement.
AB  - Continuous blood pressure (BP) measurement allows the investigation of transient
      changes in BP and thus may give insights into mechanisms of BP control. We
      validated a continuous, non-invasive BP measurement based on the pulse transit
      time (PTT), i.e., BP(PTT), by comparing it with the intra-arterial BP (BP(i.a.))
      measurement. Twelve subjects (five females and seven males) were included.
      BP(i.a.) was obtained from the radial artery using a system from ReCor Medical.
      Systolic and diastolic BP were calculated using the PTT (BP(PTT), SOMNOscreen).
      (PTT) was determined from the electrocardiogram and the peripheral pulse wave.
      The BP was modulated by application of increasing doses of dobutamine (5, 10, 20
      MUg/kg body mass). Systolic BP(PTT) and systolic BP(i.a.) correlated
      significantly (R = 0.94). The limits of agreement in the Bland-Altman plot were
      +/- 19 mmHg; the mean values differed by 1 mmHg. The correlation coefficient for
      the diastolic BP measurements was R = 0.42. The limits of agreement in the Bland
      Altman plot were +/- 18 mmHg, with a mean difference of 5 mmHg in favour of the
      BP(PTT). The study demonstrates a significant correlation between the measurement
      methods for systolic BP. The results encourage the application of PTT-based BP
      measurement for the evaluation of BP dynamics and pathological BP changes.

PMID- 25857602
TI  - Nidogen-1 is a common target of microRNAs MiR-192/215 in the pathogenesis of
      Hirschsprung's disease.
AB  - Recent studies have emphasized the important role of microRNA (miRNA) clusters
      and common target genes in disease progression. Despite the known involvement of
      the miR-192/215 family in many human diseases, its biological role in
      Hirschsprung disease (HSCR) remains undefined. In this study, we explored the
      role of the miR-192/215 family in the pathogenesis of HSCR. Quantitative real
      time PCR and western blotting measured relative expression levels of miRNAs,
      mRNAs, and proteins in 80 HSCR patients and 77 normal colon tissues. Targets were
      evaluated by dual-luciferase reporter assays, and the functional effects of miR
      192/215 on human 293T and SH-SY5Y cells were detected by the Transwell assay,
      CCK8 assay and flow cytometry. MiR-192/215 was significantly down-regulated in
      HSCR tissue samples, and their knockdown inhibited cell migration and
      proliferation in the human 293T and SH-SY5Y cell lines. Nidogen 1 (NID1) was
      confirmed as a common target gene of miR-192/215 by dual-luciferase reporter gene
      assay and its expression was inversely correlated with that of miR-192/215 in
      tissue samples and cell lines. Silencing of NID1 could rescue the extent of the
      suppressing effects by miR-192/215 inhibitor. The down-regulation of miR-192/215
      may contribute to HSCR development by targeting NID1. We proposed the following
      cascade for the proposed mechanism of miR-192/215 in the pathogenesis of
      Hirschsprung disease (HSCR) by targeting Nidogen 1 (NID1). Aberrant expression of
      miR-192/215 inhibits cell migration and cell proliferation via NID1. We think the
      miR-192/miR-215/NID1 signaling pathway may play an important role in the
      pathogenesis of HSCR. 

PMID- 25857603
TI  - Hematological and lipid profile evaluation of a hexane fraction of Costus afer
      leaves in arthritic rats.
AB  - CONTEXT: Costus afer Ker Gawl. (Costaceae) is an ethnomedical plant used as
      therapy against inflammatory disorders. OBJECTIVE: The objective of this study
      was to evaluate the hematological and lipid profile analysis of hexane fraction
      of C. afer leaves (CAHLF) in arthritic rats. MATERIALS AND METHODS: Male albino
      rats were randomly distributed into seven groups of six rats each. Rats were
      induced with arthritis using formaldehyde and Complete Freund's Adjuvant (CFA)
      for 7 and 21 d, respectively. The animals were administered orally with 50, 100,
      and 250 mg/kg CAHLF, 10 mg/kg diclofenac and prednisolone, 0.9% NaCl (control),
      and 0.9% NaCl (normal). At the end of treatment periods, blood samples were
      withdrawn and subjected to hematological and biochemical analysis using auto
      analyzer and spectrophotometric methods. RESULTS: Hematological analysis revealed
      that in formaldehyde- and CFA-induced arthritic rat models, 250 mg/kg CAHLF
      treated groups had significantly reduced (p < 0.05) hematocrit counts (HC) (30.98
      +/- 1.59% and 33.55 +/- 1.10%), white blood cell counts (WBC) (5.50 +/- 0.35 and
      4.15 +/- 0.82 * 10(9)/L), and platelet counts (PC) (401.50 +/- 48.94 and 246.33
      +/- 5.54 * 10(9)/L) compared with control HC (46.90 +/- 1.92 and 41.88 +/-
      2.19%), WBC (11.09 +/- 0.26 and 7.37 +/- 0.34 * 10(9)/L), and PC (783.67 +/-
      59.51 and 593.83 +/- 36.3 * 10(9)/L). Furthermore, blood analysis showed that
      CAHLF-treated groups had reduced total cholesterol, low-density lipoprotein
      cholesterol, and triglycerides while they had an elevated high-density
      lipoprotein compared with the control group. DISCUSSION AND CONCLUSION: Findings
      from this study indicated that CAHLF could possess immunomodulatory and
      hypolipidemic properties in arthritic rats. CAHLF could be considered as a source
      of biopharmaceutical agents in anti-arthritis drug discovery process.

PMID- 25857604
TI  - Prevention of Healthcare-Associated Pneumonia with Oral Care in Individuals
      Without Mechanical Ventilation: A Systematic Review and Meta-Analysis of
      Randomized Controlled Trials.
AB  - OBJECTIVE: Evidence is lacking on the preventive effect of oral care on
      healthcare-associated pneumonia in hospitalized patients and nursing home
      residents who are not mechanically ventilated. The primary aim of this review was
      to assess the effectiveness of oral care on the incidence of pneumonia in
      nonventilated patients. METHODS: We searched 8 databases (MEDLINE, Embase,
      CENTRAL, CINAHL, Web of Science, LILACS, ICHUSHI, and CiNii), in addition to
      trial registries and a manual search. Eligible studies were published and
      unpublished randomized controlled trials examining the effect of any method of
      oral care on reported incidence of pneumonia and/or fatal pneumonia. Relative
      risks (RR) and 95% confidence intervals were calculated. Risk of bias was
      assessed for eligible studies. RESULTS: We identified 5 studies consisting of
      1,009 subjects that met the inclusion criteria. Of these, 2 trials assessed the
      effect of chlorhexidine in hospitalized patients; 3 studies examined mechanical
      oral cleaning in nursing home residents. A meta-analysis could only be done on 4
      trials; this analysis showed a significant risk reduction in pneumonia through
      oral care interventions (RRfixed, 0.61; 95% CI, 0.40-0.91; P=.02). The effects of
      mechanical oral care alone were significant when pooled across studies. (RRfixed,
      0.61; 95% CI, 0.40-0.92; P=.02). Risk reduction for fatal pneumonia from
      mechanical oral cleaning was also significant (RRfixed, 0.41; 95% CI, 0.23-0.71;
      P=.002). Most studies had a high risk of bias. CONCLUSIONS: This analysis
      suggests a preventive effect of oral care on pneumonia in nonventilated
      individuals. This effect, however, should be interpreted with caution due to risk
      of bias in the included trials.

PMID- 25857605
TI  - Multi-omic signature of body weight change: results from a population-based
      cohort study.
AB  - BACKGROUND: Excess body weight is a major risk factor for cardiometabolic
      diseases. The complex molecular mechanisms of body weight change-induced
      metabolic perturbations are not fully understood. Specifically, in-depth
      molecular characterization of long-term body weight change in the general
      population is lacking. Here, we pursued a multi-omic approach to comprehensively
      study metabolic consequences of body weight change during a seven-year follow-up
      in a large prospective study. METHODS: We used data from the population-based
      Cooperative Health Research in the Region of Augsburg (KORA) S4/F4 cohort. At
      follow-up (F4), two-platform serum metabolomics and whole blood gene expression
      measurements were obtained for 1,631 and 689 participants, respectively. Using
      weighted correlation network analysis, omics data were clustered into modules of
      closely connected molecules, followed by the formation of a partial correlation
      network from the modules. Association of the omics modules with previous annual
      percentage weight change was then determined using linear models. In addition, we
      performed pathway enrichment analyses, stability analyses, and assessed the
      relation of the omics modules with clinical traits. RESULTS: Four metabolite and
      two gene expression modules were significantly and stably associated with body
      weight change (P-values ranging from 1.9 * 10(-4) to 1.2 * 10(-24)). The four
      metabolite modules covered major branches of metabolism, with VLDL, LDL and large
      HDL subclasses, triglycerides, branched-chain amino acids and markers of energy
      metabolism among the main representative molecules. One gene expression module
      suggests a role of weight change in red blood cell development. The other gene
      expression module largely overlaps with the lipid-leukocyte (LL) module
      previously reported to interact with serum metabolites, for which we identify
      additional co-expressed genes. The omics modules were interrelated and showed
      cross-sectional associations with clinical traits. Moreover, weight gain and
      weight loss showed largely opposing associations with the omics modules.
      CONCLUSIONS: Long-term weight change in the general population globally
      associates with serum metabolite concentrations. An integrated metabolomics and
      transcriptomics approach improved the understanding of molecular mechanisms
      underlying the association of weight gain with changes in lipid and amino acid
      metabolism, insulin sensitivity, mitochondrial function as well as blood cell
      development and function.

PMID- 25857607
TI  - Intraocular lens calcification following endothelial keratoplasty: a message for
      all cataract surgeons.

PMID- 25857606
TI  - Pupil dilation using drops vs gel: a comparative study.
AB  - PURPOSE: To compare the efficacy in pupil dilation and degree of discomfort
      between topical instillation of mydriatic drops and gel. METHODS: The study
      included 60 patients with no previous ocular history of trauma and surgery. One
      eye was dilated with two drops (tropicamide 0.5% and phenylephrine 10%), and the
      other with one drop of gel (tropicamide 0.5%+phenylephrine 5%). Pupil size was
      measured by a Colvard pupillometer at baseline and 5, 15, 30, and 45 min
      following instillation. Pain upon instillation was measured by visual analog
      scale (VAS). RESULTS: There was no difference in pupil size at baseline. Use of
      the gel achieved greater mydriasis than drops (P=0.01), and was also associated
      with lower pain scores (P=0.003). In diabetic patients, pupil size was smaller at
      baseline and following instillation of drops and gel. Use of the gel achieved an
      even greater degree of pupil dilation in this subset of patients than drops
      (P=0.019). CONCLUSIONS: Gel formulation achieved significantly greater pupil
      dilation than drops, despite a lower concentration of phenylephrine, and was also
      associated with significantly lower patient discomfort. This study is the first
      report of improved mydriatic efficacy in diabetic patients.

PMID- 25857608
TI  - Reply to 'Intraocular lens calcification following endothelial keratoplasty: a
      message for all cataract surgeons'.

PMID- 25857610
TI  - Regarding 'Transient visual loss due to reversible 'pending' central retinal
      artery occlusion in occult giant cell arteritis'.

PMID- 25857609
TI  - Topical cyclosporine to control ocular surface disease in patients with chronic
      glaucoma after long-term usage of topical ocular hypotensive medications.
AB  - PURPOSE: To evaluate changes in ocular surface and central corneal sub-basal
      nerve fiber layer (SBNFL) after topical cyclosporin therapy in chronic glaucoma
      patients on long-term topical antiglaucoma therapy. METHODS: A prospective
      comparative study of ocular surface evaluation of chronic glaucoma patients on
      long-term topical therapy treated concurrently with a topical cyclosporine 0.05%
      twice daily for 6 months and controls was done. The study parameters evaluated at
      recruitment and at the 6-month follow-up included details of topical antiglaucoma
      medications, visual acuity, intraocular pressure, ocular surface evaluation
      parameters (TBUT, Schirmers I, ocular surface staining scores and ocular surface
      disease (OSD) index score (OSDI)), central corneal sensation (Cochet Bonnett
      aesthesiometer), and central confocal microscopy to study the SBNFL density
      (SBNFLD). RESULTS: Thirty-two eyes of 16 patients with chronic glaucoma and 30
      eyes of 15 normal subjects as controls were studied. Mean TBUT, pre/post CsA
      treatment was 8.67+/-3.01/12.24+/-1.83 s (P=0.007). Mean conjunctival/corneal
      staining scores pre/post CsA treatment were 3.38+/-1.93/1.50+/-0.718 (P=0.00)
      /5.19+/-1.82/1.81+/-0.78 (P=0.098), respectively. Mean OSDI pre/post CsA
      treatment scores were 30.63+/-14.61/14.76+/-6.06 (P=0.007). Mean corneal
      sensations scores pre/post CsA treatment were 4.64+/-0.46/4.94+/-0.39 (P=0.002).
      Central corneal SBNFLD pre and post CsA treatment was 8811.35+/
      2985.29/10335.13+/-4092.064 MUm/mm(2) (P=0.0001). CONCLUSIONS: Schirmer's test,
      ocular surface staining scores, OSDI, corneal sensations, and corneal SBNFLD
      showed a statistically significant improvement following a 6-month concurrent
      topical CsA therapy.

PMID- 25857611
TI  - Chris Butler: Wants to snuggle up to bacteria.

PMID- 25857613
TI  - ICA of full complex-valued fMRI data using phase information of spatial maps.
AB  - BACKGROUND: ICA of complex-valued fMRI data is challenging because of the
      ambiguous and noisy nature of the phase. A typical solution is to remove noisy
      regions from fMRI data prior to ICA. However, it may be more optimal to carry out
      ICA of full complex-valued fMRI data, since any filtering or voxel-based
      processing may disrupt information that can be useful to ICA. NEW METHOD: We
      enable ICA of the full complex-valued fMRI data by utilizing phase information of
      estimated spatial maps (SMs). The SM phases are first adjusted to properly
      represent spatial phase changes of all voxels based on estimated time courses
      (TCs), and then these are used to segment the voxels into BOLD-related and
      unwanted voxels based on a criterion of TC real-part power maximization. Single
      subject and group phase masks are finally constructed to remove the unwanted
      voxels from the individual and group SM estimates. RESULTS: Our method
      efficiently estimated not only the task-related component but also the non-task
      related component DMN. COMPARISON WITH EXISTING METHOD(S): Our method extracted
      139-331% more contiguous and reasonable activations than magnitude-only infomax
      for the task-related component and DMN at |Z|>2.5, and detected more BOLD-related
      voxels, but eliminated more unwanted voxels than ICA of complex-valued fMRI data
      with pre-ICA de-noising. Our TC-based phase de-ambiguity exhibited higher
      accuracy and robustness than the SM-based method. CONCLUSIONS: The TC-based phase
      de-ambiguity is essential to prepare the SM phases. The SM phases provide a new
      post-ICA index for reliably identifying and suppressing the unwanted voxels.

PMID- 25857612
TI  - Acceptability and feasibility of smartphone-assisted 24 h recalls in the Chinese
      population.
AB  - OBJECTIVE: To examine the acceptability and feasibility of using smartphone
      technology to assess beverage intake and evaluate whether the feasibility of
      smartphone use is greater among key sub-populations. DESIGN: An acceptability and
      feasibility study of recording the video dietary record, the acceptability of the
      ecological momentary assessment (EMA), wearing smartphones and whether the videos
      helped participants recall intake after a cross-over validation study. SETTING:
      Rural and urban area in Shanghai, China. SUBJECTS: Healthy adults (n 110) aged 20
      40 years old. RESULTS: Most participants reported that the phone was acceptable
      in most aspects, including that videos were easy to use (70%), helped with
      recalls (77%), EMA reminders helped them record intake (75%) and apps were easy
      to understand (85%). However, 49% of the participants reported that they had
      trouble remembering to take videos of the beverages before consumption or 46%
      felt embarrassed taking videos in front of others. Moreover, 72% reported that
      the EMA reminders affected their consumption. When assessing overall
      acceptability of using smartphones, 72% of the participants were favourable
      responders. There were no statistically significant differences in overall
      acceptability for overweight v. normal-weight participants or for rural v. urban
      residents. However, we did find that the overall acceptability was higher for
      males (81%) than females (61%, P=0.017). CONCLUSIONS: Our study did not find
      smartphone technology helped with dietary assessments in a Chinese population.
      However, simpler approaches, such as using photographs instead of videos, may be
      more feasible for enhancing 24 h dietary recalls.

PMID- 25857614
TI  - Use of indocyanine green for optical analysis of cortical infarcts in
      photothrombotic ischemic brains.
AB  - BACKGROUND: Currently used techniques for diagnosing ischemic injury, such as
      magnetic resonance imaging and computed tomography, are not easily accessible for
      basic research using small animals due to their high cost and low availability.
      NEW METHOD: We investigated the dynamic recovery of infarct regions in ischemia
      injured brains using indocyanine green (ICG), which is inexpensive and readily
      available. This dye was used to visualize blood vessels and infarct area, and to
      measure blood flow after a photothrombotic ischemic operation (PIO). Mice were
      injected with ICG via the tail vein, and a time-series of fluorescence signal
      images was acquired before and after PIO. We then applied color codes to arteries
      and veins in the images and analyzed ICG intensity and dynamics. RESULTS: These
      time-series stacked images showed changes in pial vessel morphology after PIO.
      Further, a map of maximum fluorescence intensity showed an infarct in the dorsal
      cortical region. Changes in the blood flow index and mean transit time were also
      observed in the infarct region after PIO. COMPARISON WITH EXISTING METHOD(S): Our
      application of ICG imaging provided a range of information on PIO-induced
      infarcts in mice with relative ease and in a cost-effective manner. CONCLUSION:
      Our results show that optical imaging using ICG combined with a time-series
      analysis of molecular dynamics can be a useful tool for the anatomical and
      physiological monitoring of cortical ischemia.

PMID- 25857615
TI  - A novel method for delivering ramped cooling reveals rat behaviours at innocuous
      and noxious temperatures: A comparative study of human psychophysics and rat
      behaviour.
AB  - BACKGROUND: Thermal sensory testing in rodents informs human pain research. There
      are important differences in the methodology for delivering thermal stimuli to
      humans and rodents. This is particularly true in cold pain research. These
      differences confound extrapolation and de-value nociceptive tests in rodents. NEW
      METHOD: We investigated cooling-induced behaviours in rats and psychophysical
      thresholds in humans using ramped cooling stimulation protocols. A Peltier device
      mounted upon force transducers simultaneously applied a ramped cooling stimulus
      whilst measuring contact with rat hind paw or human finger pad. Rat withdrawals
      and human detection, discomfort and pain thresholds were measured. RESULTS:
      Ramped cooling of a rat hind paw revealed two distinct responses: Brief paw
      removal followed by paw replacement, usually with more weight borne than prior to
      the removal (temperature inter-quartile range: 19.1  degrees C to 2.8  degrees
      C). Full withdrawal was evoked at colder temperatures (inter quartile range: 
      11.3  degrees C to -11.8  degrees C). The profile of human cool detection
      threshold and cold pain threshold were remarkably similar to that of the rat
      withdrawals behaviours. COMPARISON: Previous rat cold evoked behaviours utilise
      static temperature stimuli. By utilising ramped cold stimuli this novel
      methodology better reflects thermal testing in patients. CONCLUSION: Brief paw
      removal in the rat is driven by non-nociceptive afferents, as is the perception
      of cooling in humans. This is in contrast to the nociceptor-driven withdrawal
      from colder temperatures. These findings have important implications for the
      interpretation of data generated in older cold pain models and consequently our
      understanding of cold perception and pain.

PMID- 25857616
TI  - Electropolymerized phenol derivatives as permselective polymers for biosensor
      applications.
AB  - Amperometric biosensors are often coated with a polymeric permselective film to
      avoid electroactive interference by reducing agents present in the target medium.
      Phenylenediamine and phenol monomers are commonly used to form these
      permselective films in the design of microsensors and biosensors. This paper aims
      to evaluate the permselectivity, stability and lifetime of polymers
      electrosynthesized using either constant potential amperometry (CPA) or cyclic
      voltammetry (CV) from naturally occurring phenylpropanoids in monomeric and
      dimeric forms (eugenol, isoeugenol, dehydrodieugenol and magnolol). Sensors were
      characterized by scanning electron microscopy and permselectivity analysis.
      Magnolol formed an electro-deposited polymer with a more defined three
      dimensional texture in comparison with the other films. The phenol-derived films
      showed different permselectivity towards H2O2 over ascorbic acid and dopamine,
      likely to be related to the thickness and compactness of the polymer. The CV
      derived films had a better permselectivity compared to the CPA-corresponding
      polymers. Based on these results, the permselectivity, stability and lifetime of
      a biosensor for glucose were studied when a magnolol coating was electro
      deposited. The structural principles governing the permselectivity of the
      magnolol-derived film are suggested to be mainly related to the conformational
      flexibility of this monomer. Newly designed biosensors, coated with
      electropolymerized natural phenol derivatives, may represent promising analytical
      devices for different application fields. 

PMID- 25857617
TI  - Oxidative stress involving changes in Nrf2 and ER stress in early stages of
      Alzheimer's disease.
AB  - Oxidative stress and endoplasmic reticulum (ER) stress have been associated with
      Alzheimer's disease (AD) progression. In this study we analyzed whether oxidative
      stress involving changes in Nrf2 and ER stress may constitute early events in AD
      pathogenesis by using human peripheral blood cells and an AD transgenic mouse
      model at different disease stages. Increased oxidative stress and increased
      phosphorylated Nrf2 (p(Ser40)Nrf2) were observed in human peripheral blood
      mononuclear cells (PBMCs) isolated from individuals with mild cognitive
      impairment (MCI). Moreover, we observed impaired ER Ca2+ homeostasis and
      increased ER stress markers in PBMCs from MCI individuals and mild AD patients.
      Evidence of early oxidative stress defense mechanisms in AD was substantiated by
      increased p(Ser40)Nrf2 in 3month-old 3xTg-AD male mice PBMCs, and also with
      increased nuclear Nrf2 levels in brain cortex. However, SOD1 protein levels were
      decreased in human MCI PBMCs and in 3xTg-AD mice brain cortex; the latter further
      correlated with reduced SOD1 mRNA levels. Increased ER stress was also detected
      in the brain cortex of young female and old male 3xTg-AD mice. We demonstrate
      oxidative stress and early Nrf2 activation in AD human and mouse models, which
      fails to regulate some of its targets, leading to repressed expression of
      antioxidant defenses (e.g., SOD-1), and extending to ER stress. Results suggest
      markers of prodromal AD linked to oxidative stress associated with Nrf2
      activation and ER stress that may be followed in human peripheral blood
      mononuclear cells.

PMID- 25857618
TI  - Transient receptor potential channel M2 contributes to neointimal hyperplasia in
      vascular walls.
AB  - BACKGROUND: A hallmark of atherosclerosis is progressive intimal thickening
      (namely neointimal hyperplasia), which leads to occlusive vascular diseases. Over
      production of reactive oxygen species (ROS) and alteration of Ca2+ signaling are
      among the key factors contributing to neointimal growth. In the present study, we
      investigated the role of TRPM2, a ROS-sensitive Ca2+ entry channel, in neointimal
      hyperplasia. METHODS AND RESULTS: Perivascular cuffs were used to induce
      neointimal hyperplasia in rat/mouse arteries. Immunostaining showed numerous
      TRPM2-positive smooth muscle cells in neointimal regions. ROS were over-produced
      and PCNA-positive proliferating cells were numerous in the neointimal regions.
      The neointimal hyperplasia was substantially reduced in Trpm2 knockout mice
      compared with wild-type mice. In the cultured rat/mouse aortic smooth muscle
      cells, H2O2 treatment was found to stimulate cell proliferation and migration.
      The effect of H2O2 was reduced by a TRPM2-specific blocking antibody TM2E3 or
      Trpm2 knockout. The signaling molecules downstream of TRPM2 were found to be Axl
      and Akt. CONCLUSIONS: These data suggest a critical functional role of TRPM2 in
      the progression of neointimal hyperplasia. The study also highlights the
      possibility of targeting TRPM2 as a potential therapeutic option for the
      treatment of occlusive vascular diseases.

PMID- 25857619
TI  - Altered ROS production, NF-kappaB activation and interleukin-6 gene expression
      induced by electrical stimulation in dystrophic mdx skeletal muscle cells.
AB  - Duchenne muscular dystrophy is a fatal X-linked genetic disease, caused by
      mutations in the dystrophin gene, which cause functional loss of this protein.
      This pathology is associated with an increased production of reactive oxygen
      (ROS) and nitrogen species. The aim of this work was to study the alterations in
      NF-kappaB activation and interleukin-6 (IL-6) expression induced by membrane
      depolarization in dystrophic mdx myotubes. Membrane depolarization elicited by
      electrical stimulation increased p65 phosphorylation, NF-kappaB transcriptional
      activity and NF-kappaB-dependent IL-6 expression in wt myotubes, whereas in mdx
      myotubes it had the opposite effect. We have previously shown that depolarization
      induced intracellular Ca2+ increases and ROS production are necessary for NF
      kappaB activation and stimulation of gene expression in wt myotubes. Dystrophic
      myotubes showed a reduced amplitude and area under the curve of the Ca2+
      transient elicited by electrical stimulation. On the other hand, electrical
      stimuli induced higher ROS production in mdx than wt myotubes, which were blocked
      by NOX2 inhibitors. Moreover, mRNA expression and protein levels of the NADPH
      oxidase subunits: p47phox and gp91phox were increased in mdx myotubes. Looking at
      ROS-dependence of NF-kappaB activation we found that in wt myotubes external
      administration of 50 MUM H2O2 increased NF-kappaB activity; after administration
      of 100 and 200 MUM H2O2 there was no effect. In mdx myotubes there was a dose
      dependent reduction in NF-kappaB activity in response to external administration
      of H2O2, with a significant effect of 100 MUM and 200 MUM, suggesting that ROS
      levels are critical for NF-kappaB activity. Prior blockage with NOX2 inhibitors
      blunted the effects of electrical stimuli in both NF-kappaB activation and IL-6
      expression. Finally, to ascertain whether stimulation of NF-kappaB and IL-6 gene
      expression by the inflammatory pathway is also impaired in mdx myotubes, we
      studied the effect of lipopolysaccharide on both NF-kappaB activation and IL-6
      expression. Exposure to lipopolysaccharide induced a dramatic increase in both NF
      kappaB activation and IL-6 expression in both wt and mdx myotubes, suggesting
      that the altered IL-6 gene expression after electrical stimulation in mdx muscle
      cells is due to dysregulation of Ca2+ release and ROS production, both of which
      impinge on NF-kappaB signaling. IL-6 is a key metabolic modulator that is
      released by the skeletal muscle to coordinate a multi-systemic response (liver,
      muscle, and adipocytes) during physical exercise; the alteration of this response
      in dystrophic muscles may contribute to an abnormal response to contraction and
      exercise.

PMID- 25857620
TI  - Future perspectives: Moving towards NCL treatments.
AB  - Clinicians, basic researchers, representatives from pharma and families from
      around the world met in Cordoba, Argentina in October, 2014 to discuss recent
      research progress at the 14th International Congress on Neuronal Ceroid
      Lipofuscinoses (NCLs; Batten disease), a group of clinically overlapping fatal,
      inherited lysosomal disorders with primarily neurodegenerative symptoms. This
      brief review article will provide perspectives on the anticipated future
      directions of NCL basic and clinical research as we move towards improved
      diagnosis, care and treatment of NCL patients. This article is part of a Special
      Issue entitled: Current Research on the Neuronal Ceroid Lipofuscinoses (Batten
      Disease). 

PMID- 25857621
TI  - Involvement of activated SUMO-2 conjugation in cardiomyopathy.
AB  - Sumoylation is a posttranslational modification that regulates a wide spectrum of
      cellular activities. Cardiomyopathy is the leading cause of heart failure.
      Whether sumoylation, particularly SUMO-2/3 conjugation, is involved in
      cardiomyopathy has not been investigated. We report here that SUMO-2/3
      conjugation was elevated in the human failing hearts, and we investigated the
      impact of increased SUMO-2 conjugation on heart function by using the gain-of
      function approach in mice, in which cardiac specific expression of constitutively
      active SUMO-2 was governed by alpha myosin heavy chain promoter (MHC-SUMO-2
      transgenic, SUMO-2-Tg). Four of five independent SUMO-2-Tg mouse lines exhibited
      cardiomyopathy with various severities, ranging from acute heart failure leading
      to early death to the development of chronic cardiomyopathy with aging. We
      further revealed that SUMO-2 directly regulated apoptotic process by at least
      partially targeting calpain 2 and its natural inhibitor calpastatin. SUMO
      conjugation to calpain 2 promoted its enzymatic activity, and SUMO attachment to
      calpastatin mainly promoted its turnover and altered its subcellular
      distribution. Thus, enhanced SUMO-2 conjugation led to increased apoptosis and
      played a pathogenic role in the development of cardiomyopathy and heart failure. 

PMID- 25857622
TI  - Postdischarge breastfeeding outcomes of infants with complex anomalies that
      require surgery.
AB  - OBJECTIVE: To examine the duration and exclusivity of breastfeeding and provision
      of human milk among infants with complex anomalies that require surgery
      postdischarge from a neonatal intensive care unit (NICU). DESIGN: Prospective
      cohort study. SETTING: A tertiary care children's hospital with a fetal
      diagnostic and treatment center, special delivery unit, and NICU. PARTICIPANTS:
      Mothers who had delivered infants with complex anomalies that require surgery
      between 2009 and 2012 (N = 165). METHODS: Phone interviews were used for data
      collection and were analyzed using descriptive statistics methods. RESULTS: The
      average duration of breastfeeding/provision of human milk was 8 months. The
      percentage of infants who received human milk at 6 months was 60.1% (n = 98/163,;
      p = .0063) and at 12 months was 34.5% (n = 57/165, p = .023). Of infants in this
      cohort, the percentage of those infants exclusively receiving human milk was
      54.3% (n = 89/164, p = .0004) at 3 months of age and 35.6% (n = 58/163, p <
      .0001) at age 6 months. Another clinically important finding is that 30.7% of the
      cohort required gavage feeds postdischarge from the NICU. CONCLUSION: Even for
      the most surgically complex infant/mother dyads, breastfeeding outcomes can
      improve significantly with a strong prenatal lactation program, nursing staff
      with specific breastfeeding education, and a hospital culture that values and
      supports breastfeeding and the provision of human milk. These findings support
      the use of hospital-grade electric breast pumps postdischarge for families of
      infants with complex anomalies that require surgery, as approximately one third
      of the cohort went home on tube feeds and their mothers continued to pump their
      breast milk at home.

PMID- 25857623
TI  - Surgical treatment for medically refractory focal epilepsy in a patient with
      fragile X syndrome.
AB  - RATIONALE: Medication resistant temporal lobe epilepsy occurs in a small
      population of patients with fragile X syndrome. We present the case of a 24-year
      old man with medically refractory temporal lobe epilepsy and fragile X syndrome
      who underwent left anterior temporal lobectomy resulting in cessation of
      seizures. METHODS: Our patient was diagnosed with fragile X syndrome with a fully
      mutated, fully methylated FMR1 gene resulting in 572 CGG repeats. He developed
      seizures initially controlled with Depakote monotherapy, but progressed to become
      medically refractive to combination treatment with Depakote, lamotrigine and
      zonisamide. Prolonged video EEG monitoring revealed interictal left temporal
      sharp waves and slowing as well as subclinical and clinical seizures, each with
      left temporal onset. 3T MRI was consistent with left mesial temporal sclerosis.
      After discussing the case in our multidisciplinary surgical epilepsy conference,
      he was referred for presurgical evaluation including neuropsychological testing
      and Wada testing. RESULTS: He underwent an asleep left anterior temporal
      lobectomy, sparing the superior temporal gyrus. Pathology showed neuronal loss
      and gliosis in the hippocampus and amygdala. Twelve months after surgery, the
      patient has not experienced a seizure. He is described by his parents as less
      perseverative and less restless. CONCLUSIONS: We have presented the case of a 24
      year-old-man with fragile X syndrome who underwent successful left anterior
      temporal lobectomy for the treatment of medically refractory epilepsy who is now
      seizure free without further functional impairment. This case report demonstrates
      the feasibility of surgical treatment for a patient with comorbid fragile X
      syndrome and mesial temporal sclerosis.

PMID- 25857624
TI  - Hereditary Hemorrhagic Telangiectasia presenting as migraine: a case report.
AB  - BACKGROUND: Hemorrhagic Hereditary Telangiectasia (HHT) is an autosomal dominant
      disease characterized by the presence of multiple arteriovenous malformations
      (AVMs). Migraine is described in association with HHT in adulthood, while only
      few paediatric cases are reported in the literature. AIM: In this paper, we
      describe an atypical case of HHT in a 7-year-old boy, who presented severe and
      recurrent episodes of migraine-like headache as the first symptom of the disease.
      METHODS: The patient was accurately investigated both clinically (general,
      neurological and dermatological examinations), instrumentally
      (electroencephalogram, brain magnetic resonance, transcranic Eco-color-Doppler,
      contrast echocardiography and enhanced chest computed tomography) and
      genetically. RESULTS: Familial history was positive for HHT in the paternal line.
      Both general and neurological examination were normal. Brain magnetic resonance
      imaging showed a minor old infarct in the right parietal and occipital lobes.
      Transcranic Eco-color-Doppler, contrast echocardiography and enhanced chest
      computed tomography revealed a pulmonary AVM. Cephalalgia resolved after
      transcatheter embolotherapy. A genetic test, identifying the mutation in endoglin
      gene both in the patient and in the father, confirmed the suspected diagnosis of
      HHT. CONCLUSIONS: Although headache is rarely reported in children as the first
      symptom of HHT, we warn clinicians on this possible link, as a promptly diagnosis
      is advisable in order to prevent potential complications.

PMID- 25857625
TI  - Avoiding verisimilitude when modelling ecological responses to climate change:
      the influence of weather conditions on trapping efficiency in European badgers
      (Meles meles).
AB  - The signal for climate change effects can be abstruse; consequently,
      interpretations of evidence must avoid verisimilitude, or else misattribution of
      causality could compromise policy decisions. Examining climatic effects on wild
      animal population dynamics requires ability to trap, observe or photograph and to
      recapture study individuals consistently. In this regard, we use 19 years of data
      (1994-2012), detailing the life histories on 1179 individual European badgers
      over 3288 (re-) trapping events, to test whether trapping efficiency was
      associated with season, weather variables (both contemporaneous and time lagged),
      body-condition index (BCI) and trapping efficiency (TE). PCA factor loadings
      demonstrated that TE was affected significantly by temperature and precipitation,
      as well as time lags in these variables. From multi-model inference, BCI was the
      principal driver of TE, where badgers in good condition were less likely to be
      trapped. Our analyses exposed that this was enacted mechanistically via weather
      variables driving BCI, affecting TE. Notably, the very conditions that militated
      for poor trapping success have been associated with actual survival and
      population abundance benefits in badgers. Using these findings to parameterize
      simulations, projecting best-/worst-case scenario weather conditions and BCI
      resulted in 8.6% +/- 4.9 SD difference in seasonal TE, leading to a potential
      55.0% population abundance under-estimation under the worst-case scenario; 38.6%
      over-estimation under the best case. Interestingly, simulations revealed that
      while any single trapping session might prove misrepresentative of the true
      population abundance, due to weather effects, prolonging capture-mark-recapture
      studies under sub-optimal conditions decreased the accuracy of population
      estimates significantly. We also use these projection scenarios to explore how
      weather could impact government-led trapping of badgers in the UK, in relation to
      TB management. We conclude that population monitoring must be calibrated against
      the likelihood that weather conditions could be altering trap success directly,
      and therefore biasing model design. 

PMID- 25857626
TI  - Aldosterone down-regulates the slowly activated delayed rectifier potassium
      current in adult guinea pig cardiomyocytes.
AB  - BACKGROUND AND PURPOSE: There is emerging evidence that the mineralocorticoid
      hormone aldosterone is associated with arrhythmias in cardiovascular disease.
      However, the effect of aldosterone on the slowly activated delayed rectifier
      potassium current (IK s ) remains poorly understood. The present study was
      designed to investigate the modulation of IK s by aldosterone. EXPERIMENTAL
      APPROACH: Adult guinea pigs were treated with aldosterone for 28 days via osmotic
      pumps. Standard glass microelectrode recordings and whole-cell patch-clamp
      techniques were used to record action potentials in papillary muscles and IK s in
      ventricular cardiomyocytes. KEY RESULTS: The aldosterone-treated animals
      exhibited a prolongation of the QT interval and action potential duration with a
      higher incidence of early afterdepolarizations. Patch-clamp recordings showed a
      significant down-regulation of IK s density in the ventricular myocytes of these
      treated animals. These aldosterone-induced electrophysiological changes were
      fully prevented by a combined treatment with spironolactone, a mineralocorticoid
      receptor (MR) antagonist. In addition, in in vitro cultured ventricular
      cardiomyocytes, treatment with aldosterone (sustained exposure for 24 h)
      decreased the IK s density in a concentration-dependent manner. Furthermore, a
      significant corresponding reduction in the mRNA/protein expression of IKs channel
      pore and auxiliary subunits, KCNQ1 and KCNE1 was detected in ventricular tissue
      from the aldosterone-treated animals. CONCLUSIONS AND IMPLICATIONS: Aldosterone
      down-regulates IK s by inhibiting the expression of KCNQ1 and KCNE1, thus
      delaying the ventricular repolarization. These results provide new insights into
      the mechanism underlying K(+) channel remodelling in heart disease and may
      explain the highly beneficial effects of MR antagonists in HF.

PMID- 25857627
TI  - Punica granatum and its therapeutic implications on breast carcinogenesis: A
      review.
AB  - Punica granatum has a recorded history of pharmacological properties which can be
      attributed to its rich reservoir of phytochemicals. Investigations in recent
      years have established its tremendous potential as an antitumorogenic agent
      against various cancers including breast cancer, which is the second leading
      cause of cancer-related deaths in women. The plausible role of Punica as a
      therapeutic agent, as an adjuvant in chemotherapy, and its dietary implications
      as chemopreventive agent in breast cancer have been explored. Mechanistic studies
      have revealed that Punica extracts and its components, individually or in
      combination, can modulate and target key proteins and genes involved in breast
      cancer. Our earlier finding also demonstrated the role of methanolic extract of
      pomegranate pericarp in reducing proliferation in breast cancer by binding to
      estrogen receptor at the same time not affecting uterine weight unlike estradiol
      or tamoxifen. This review analyses other plausible mechanisms of Punica in
      preventing the progression of breast cancer and how it can possibly be a
      therapeutic agent by acting at various steps of carcinogenesis including
      proliferation, invasion, migration, metastasis, angiogenesis, and inflammation
      via various molecular mechanisms.

PMID- 25857628
TI  - Patient adaptive maximal resolution magnetic resonance myocardial stress
      perfusion imaging.
AB  - PURPOSE: To demonstrate the feasibility of an automatic adaptive acquisition
      sequence. Magnetic resonance perfusion pulse sequences often leave potential
      acquisition time unused in patients with lower heart-rates (HR) and smaller body
      size. MATERIALS AND METHODS: A perfusion technique was developed that
      automatically adapts to HR and field-of-view by maximizing in-plane spatial
      resolution while maintaining temporal resolution every cardiac cycle. Patients (n
      = 10) and volunteers (n = 10) were scanned with both a standard resolution and
      adaptive method. Image quality was scored, signal-to-noise ratio (SNR)
      calculated, and width of dark-rim artifact (DRA) measured. RESULTS: The acquired
      spatial resolution of the adaptive sequence (1.92 * 1.92 mm(2)  +/- 0.34) was
      higher than the standard resolution (2.42 * 2.42 mm(2) ) (P < 0.0001). Mean DRA
      width was reduced using the adaptive pulse sequence (1.94 +/- 0.60 mm vs. 2.82 +/
      0.65 mm, P < 0.0001). The signal-to-noise ratio (SNR) was higher with the
      standard pulse sequence (6.7 +/- 2.2 vs. 3.8 +/- 1.8, P < 0.0001). There was no
      difference in image quality score between sequences in either volunteers (1.1 +/-
      0.31 vs. 1.0 +/- 0.0, P = 0.34) or patients (1.3 +/- 0.48 vs. 1.3 +/- 0.48, P =
      1.0). CONCLUSION: Optimizing the use of available imaging time during first-pass
      perfusion with a magnetic resonance imaging pulse sequence that adapts image
      acquisition duration to HR and patient size is feasible. Acquired in-plane
      spatial resolution is improved, the DRA is reduced, and while SNR is reduced with
      the adaptive sequence consistent with the lower voxel size used, image quality is
      maintained.

PMID- 25857629
TI  - Contribution of portal-drained viscera to heat production in Iberian gilts fed a
      low-protein diet: comparison to Landrace.
AB  - BACKGROUND: In terms of whole-body metabolism, visceral tissues have a
      disproportionate influence with respect to their masses, and under certain
      circumstances their high metabolic rate may compromise nutrient availability to
      the tissues of productive/economic interest. The low energy efficiency of Iberian
      compared to modern breeds could be partly explained by the contribution of portal
      drained viscera to heat production. The objective of this study was to determine
      the relative contribution of portal-drained viscera heat production (PDVHP) to
      total heat production (THP) in Iberian and Landrace gilts fed a diet with low
      protein content. RESULTS: Compared to Landrace, Iberian gilts (29 +/- 0.9 kg body
      weight) had lower pre- and postprandial portal vein blood flow (654 vs. 965, and
      746 vs. 1133 mL min(-1) , respectively; P < 0.01), postprandial PDVHP (3.09 vs.
      3.88 kJ h(-1)  kg(-0.75) ; P < 0.01) and PDVHP/THP ratio (0.08 vs. 0.13; P <
      0.05), and greater THP (38.5 vs. 31.8 kJ h(-1)  kg(-0.75) ; P < 0.05), when
      offered 0.25 of their daily ration in a 6 h sampling period. CONCLUSION: In spite
      of the low energetic efficiency and growth rate of Iberian compared to modern
      breeds, the contribution of PDV energy expenditure relative to THP was lower in
      Iberian compared to Landrace gilts in the present study.

PMID- 25857631
TI  - Neuropathic Pain Components in Patients with Cancer: Prevalence, Treatment, and
      Interference with Daily Activities.
AB  - BACKGROUND: Pain and neuropathic symptoms impact quality of life of patients with
      cancer. To obtain more insight in the prevalence, severity, and treatment of
      neuropathic symptoms in patients with cancer and their interference with daily
      activities, we conducted a cross-sectional study at the outpatient clinic of a
      Dutch university hospital. METHODS: A cross-sectional study among outpatients
      with cancer. To identify pain, its intensity, quality, and interference with
      daily activities, the Brief Pain Inventory (BPI) was used. Neuropathic symptoms
      were identified with the Douleur Neuropathique (DN4) interview and pain
      characteristics with the McGill Pain Questionnaire (MPQ). Pain medication and
      adjuvant analgesics were also collected with a prestructured questionnaire.
      Descriptives, chi-squared tests, t-tests, and a logistic regression analysis were
      conducted. RESULTS: 892 patients completed the questionnaires. Twenty-three
      percent (n = 204) reported moderate to severe pain, and 19% (n = 170) scored
      positive on neuropathic symptoms (DN4 >= 3). Particularly in patients with a
      rating on a numeric rating scale (NRS) < 5, existence of neuropathic symptoms
      significantly increased interference with daily activities. Of patients with
      neuropathic symptoms, 8% received adjuvant pain treatment. Receiving curative
      treatment, using a systemic drug with neurotoxicity, having had an operation, and
      having had a lymph node dissection independently contributed to having
      neuropathic symptoms. CONCLUSIONS: This study shows that over 40% of the patients
      with moderate to severe pain also have neuropathic symptoms, causing increased
      interference with daily activities. Most of these patients do not receive
      adjuvant analgesics. There is a need to improve management of neuropathic
      symptoms in patients with cancer.

PMID- 25857633
TI  - Factors affecting maternal serum magnesium levels during long-term magnesium
      sulfate tocolysis in singleton and twin pregnancy.
AB  - AIM: Our aim was to determine factors that affect maternal serum magnesium (Mg)
      levels, to help ensure the safety and efficacy of long-term magnesium sulfate
      (MgSO4 ) therapy for threatened preterm labor in singleton and twin pregnancies.
      MATERIAL AND METHODS: We retrospectively and arbitrarily studied 100 patients
      (singleton pregnancy, n = 65; twin pregnancy, n = 35) who received i.v. MgSO4 for
      >48 h for tocolysis of threatened preterm labor. We used multiple regression
      analysis to investigate the functional relations between the candidate factors
      and maternal serum Mg levels. RESULTS: MgSO4 was administered as a loading dose
      of 3 g for 1 h followed by a maintenance dose of 1.0-2.0 g/h. There were no
      maternal severe adverse events related to the elevated Mg levels in any of the
      subjects. The results of multiple regression analysis revealed that total dose of
      MgSO4 for 24 h before blood collection (g/day), total serum protein level (g/dL),
      serum total calcium level (mg/dL), serum creatinine level (mg/dL) and maternal
      bodyweight (kg) significantly affected maternal serum Mg levels in both singleton
      and twin pregnancies (all P-values were < 0.001). Gestational age (weeks) and
      period of MgSO4 administration (days) at blood collection had no significant
      effect in singleton or twin pregnancies. CONCLUSION: Our study statistically
      shows that dose of MgSO4 , total serum protein level, serum total calcium level,
      serum creatinine level and maternal bodyweight are key factors to achieving safe
      and effective long-term tocolysis with MgSO4 in not only singleton but also twin
      pregnancies.

PMID- 25857630
TI  - NF-kappaB and stat3 transcription factor signatures differentiate HPV-positive
      and HPV-negative head and neck squamous cell carcinoma.
AB  - Using high-throughput analyses and the TRANSFAC database, we characterized TF
      signatures of head and neck squamous cell carcinoma (HNSCC) subgroups by
      inferential analysis of target gene expression, correcting for the effects of DNA
      methylation and copy number. Using this discovery pipeline, we determined that
      human papillomavirus-related (HPV+) and HPV- HNSCC differed significantly based
      on the activity levels of key TFs including AP1, STATs, NF-kappaB and p53.
      Immunohistochemical analysis confirmed that HPV- HNSCC is characterized by co
      activated STAT3 and NF-kappaB pathways and functional studies demonstrate that
      this phenotype can be effectively targeted with combined anti-NF-kappaB and anti
      STAT therapies. These discoveries correlate strongly with previous findings
      connecting STATs, NF-kappaB and AP1 in HNSCC. We identified five top-scoring pair
      biomarkers from STATs, NF-kappaB and AP1 pathways that distinguish HPV+ from HPV-
      HNSCC based on TF activity and validated these biomarkers on TCGA and on
      independent validation cohorts. We conclude that a novel approach to TF pathway
      analysis can provide insight into therapeutic targeting of patient subgroup for
      heterogeneous disease such as HNSCC. 

PMID- 25857634
TI  - Genetic Polymorphisms in the Toll-like Receptor 10, Interleukin (IL)17A and IL17F
      Genes Differently Affect the Risk for Tuberculosis in Croatian Population.
AB  - Proinflammatory conditions leading to activation of macrophages via interferon
      gamma bear an important role in host defence against intracellular bacteria such
      as Mycobacterium tuberculosis (Mt). Interleukin-17 plays a similar role, as it
      appears to be also an activator of macrophages. Recently, the TLR-10 was
      identified as an anti-inflammatory factor that exerts its action via association
      with the TLR-2 chain at the cell surface of macrophages, the latter being an Mt
      binding protein. We have previously found that gene polymorphisms that either
      inactivate the TLR2 gene product or have a dominant-negative role are associated
      with tuberculosis (TB) in Croatian population. We have now extended our survey
      and found that single nucleotide polymorphism (SNP) in TLR10 (rs11096957) is
      associated with risk for TB. Homozygotes carrying the A allele are associated
      with predisposition to disease as analysed by the dominant model of inheritance.
      In contrast, SNPs in the proinflammatory IL17A and IL17F genes (rs2275913 and
      rs763780, respectively), found previously to correlate with the disease
      occurrence in Chinese population, were not significantly associated with
      tuberculosis in the Croatian population. 

PMID- 25857635
TI  - Differences Exist in the Left and Right Sciatic Nerves of Naive Rats and Cats.
AB  - The sciatic nerve of rats and cats is commonly used in experimental models of
      peripheral nerve injury and repair, as well as experiments involving peripheral
      nerve electrode implantation. In such experiments, morphometric parameters from
      the implanted nerve are commonly evaluated and compared to control values
      obtained from the contralateral nerves. However, this may not be an appropriate
      approach as differences may naturally exist in the structure of the two nerves
      owing to developmental or behavioral asymmetry. Additionally, in the cat,
      baseline values for standard morphometric parameters are not well established. In
      this study, we characterized fascicle area, fiber count, fiber density, fiber
      packing, mean g-ratio, and fiber diameter distributions in the rat and cat, as
      well as investigated the potential for naturally occurring sided differences in
      these parameters in both species. We also investigated whether animal age or
      location along the nerve influenced these parameters. We found that sided or
      left/right leg differences exist in some parameters in both the rat and the cat,
      calling into question the validity of using the contralateral nerve as a control.
      We also found that animal age and location along the nerve can make significant
      differences in the parameters tested, establishing the importance of using
      control nerves from age- and behaviorally matched animals whose morphometric
      parameters are collected and compared from the same location.

PMID- 25857637
TI  - RH diversity in Mali: characterization of a new haplotype RHD*DIVa/RHCE*ceTI(D2).
AB  - BACKGROUND: Knowledge of RH variants in African populations is critical to
      improving transfusion safety in countries with populations of African ancestry
      and to providing valuable information and direction for future development of
      transfusion in Africa. The purpose of this report is to describe RH diversity in
      individuals from Mali. STUDY DESIGN AND METHODS: Blood samples collected from 147
      individuals self-identified as Dogon and Fulani were analyzed for Rh antigens and
      alleles. RESULTS: The most common RHD allele variant was RHD*DAU0. Five predicted
      partial-D phenotypes were attributed to RHD*DAU3 or RHD*DIVa. Neither RHD*DAR nor
      RHD*DIIIa was found. Investigation of RHCE revealed three predicted partial-e
      antigens encoded by RHCE*ce(254G) in trans to RHCE*cE. Regarding C antigen, 28
      Fulani typed as C+ and 16 of 28 harbored at least one RHCE*Ce-D(4)-ce, two being
      homozygous and predicted to show a rare RH:32,-46 phenotype. A new RHCE*ceTI with
      replacement of Exon 2 by RHD (RHCE*ceTI(D2)) was identified in Dogon and was
      identified by inheritance study to be in cis to RHD*DIVa. These samples typed C-
      with anti-C polyclonal antibody and monoclonal antibodies (MoAbs) MS24,
      P3X2551368+MS24, and MS273, but positive with anti-RhCe MoAb-BS58. The same
      pattern was observed in sample with RHD*DIVa/RHCE*ceTI. CONCLUSION: Our survey
      indicated an uneven distribution of RH variant alleles between Dogon and Fulani,
      suggesting that study in well-documented cohorts is warranted. A high incidence
      of predicted partial-C phenotype encoded by RHCE*Ce-D(4)-ce was found in Fulani.
      Further study will also be needed to clarify the clinical significance of the new
      DIVa/ceTI(D2) haplotype encoding partial D and variant ce antigens.

PMID- 25857636
TI  - Solution structure and properties of AlgH from Pseudomonas aeruginosa.
AB  - In Pseudomonas aeruginosa, the algH gene regulates the cellular concentrations of
      a number of enzymes and the production of several virulence factors, and is
      suggested to serve a global regulatory function. The precise mechanism by which
      the algH gene product, the AlgH protein, functions is unknown. The same is true
      for AlgH family members from other bacteria. In order to lay the groundwork for
      understanding the physical underpinnings of AlgH function, we examined the
      structure and physical properties of AlgH in solution. Under reducing conditions,
      results of NMR, electrophoretic mobility, and sedimentation equilibrium
      experiments indicate AlgH is predominantly monomeric and monodisperse in
      solution. Under nonreducing conditions intra and intermolecular disulfide bonds
      form, the latter promoting AlgH oligomerization. The high-resolution solution
      structure of AlgH reveals alpha/beta-sandwich architecture fashioned from ten
      beta strands and seven alpha helices. Comparison with available structures of
      orthologues indicates conservation of overall structural topology. The region of
      the protein most strongly conserved structurally also shows the highest amino
      acid sequence conservation and, as revealed by hydrogen-deuterium exchange
      studies, is also the most stable. In this region, evolutionary trace analysis
      identifies two clusters of amino acid residues with the highest evolutionary
      importance relative to all other AlgH residues. These frame a partially solvent
      exposed shallow hydrophobic cleft, perhaps identifying a site for intermolecular
      interactions. The results establish a physical foundation for understanding the
      structure and function of AlgH and AlgH family proteins and should be of general
      importance for further investigations of these and related proteins.

PMID- 25857639
TI  - The physiological background behind and course of development of the first proton
      pump inhibitor.
AB  - Gastric acid secretion and its related diseases and their treatments have
      generated important contributions to gastroenterology and its development as an
      autonomous medical specialty. The discovery of histamine receptors and the
      subsequent H2-receptor antagonists (1972) changed the practice of
      gastroenterology forever. Gastric acid was effectively inhibited and ulcers could
      be healed to an extent which had not previously been seen. An additional
      milestone along the same avenue was offered by the identification of hydrogen
      potassium adenosine triphosphatase (H(+)K(+)-ATPase) as the proton pump of the
      parietal cell. Nowadays, proton pump inhibitors (PPIs) are widely used. However,
      we need to reconsider the physiology and pathophysiology of acid secretion and
      its long-term inhibition to avoid potential negative effects on general health.
      PPIs are generally considered among the safest class of drugs. In the late 1960s,
      a research project was initiated to develop an antisecretory drug which could be
      used in acid hypersecretory disease states such as peptic ulcer disease based on
      the option to synthesize a local anesthetic drug that could be orally
      administered and therefore have its main action on the gastrin cells. This
      concept was soon found to be a blind track and further development of the basic
      compounds CMN131 by the synthesis of H77/67 were found to be active in the
      gastric acid secretion, and the benzimidazol analog of H77/67 was then
      synthesized a year later and was tested and found to exert powerful acid
      inhibitory effects. Binding studies with the substituted benzimidazoles clarified
      specific binding to H+/K+/ATPase in the secretory vesicles of the parietal cells.
      Since weak bases like aminopyrine accumulate in the acid compartment of the
      parietal cells, the chemists changed the substituents of the heterocyclic ring
      and obtained a compound with a weak base property with an optimal PkA value,
      thereby maximizing the accumulation of the compound at the site of action. This
      compound H168/68 was synthesized in 1979 and was given the generic name
      omeprazole. Omeprazole was soon shown to be a very potent inhibitor of the proton
      pump in vitro as well as in preparation from the human stomach tissue.
      Pharmacological studies showed long-lasting effect on acid secretion and a
      specific binding to the target site and soon found the compound to exert unique
      therapeutic effects. CONCLUSION: The development of the first PPI omeprazole
      represents an exceptional example of a unique and fruitful collaboration between
      people with in-depth knowledge of gastric physiology and pharmacology. Frontline
      expertise in biochemistry and applied clinical science were added to these
      components, resulting in one of the greatest therapeutic advances during the last
      decades of the former century.

PMID- 25857638
TI  - Prevalence of and risk factors for degenerative mitral valve disease in dogs
      attending primary-care veterinary practices in England.
AB  - BACKGROUND: To date, epidemiological studies on degenerative mitral valve disease
      (DMVD) in dogs have largely reported referral caseloads or been limited to
      predisposed breeds. Analysis of primary-care data to identify factors associated
      with DMVD would help clinicians identify high-risk individuals and improve
      understanding. OBJECTIVES: To estimate the prevalence of and identify risk
      factors for DMVD in dogs attending primary-care veterinary practices in England.
      ANIMALS: Cases were identified within the electronic patient records of 111,967
      dogs attending 93 practices. Four hundred and 5 dogs were diagnosed with DMVD
      (diagnosed cases) and a further 3,557 dogs had a heart murmur (HM) consistent
      with DMVD (possible cases). METHODS: Retrospective cross-sectional study design.
      Prevalence was adjusted for the sampling approach. Mixed effects logistic
      regression models identified factors associated with DMVD. RESULTS: Prevalence
      estimates of diagnosed DMVD and HMs consistent with DMVD (both diagnosed and
      possible cases) were 0.36% (95% confidence interval [CI]: 0.29-0.45) and 3.54%
      (95% CI: 3.26-3.84) respectively. In the multivariable analysis, males had higher
      odds of diagnosed DMVD than did females (odds ratio [OR] 1.40, 95% CI: 1.12
      1.74). Insured dogs had increased odds of DMVD compared with noninsured dogs (OR
      3.56, 95% CI: 2.79-4.55) and dogs >=20 kg had approximately half the odds of DMVD
      diagnosis compared with dogs <20 kg (OR 0.51, 95% CI: 0.36-0.74). Strong
      associations between a DMVD diagnosis and individual breeds and age were
      identified. CONCLUSIONS AND CLINICAL IMPORTANCE: Degenerative mitral valve
      disease was a common disorder in practice-attending dogs. Knowledge of identified
      risk factors for DMVD could improve clinical diagnosis and direct future
      research.

PMID- 25857640
TI  - Improvement in metabolic effects by dietary intervention is dependent on the
      precise nature of the developmental programming challenge.
AB  - Predisposition to offspring metabolic dysfunction due to poor maternal nutrition
      differs with the developmental stage at exposure. Post-weaning nutrition also
      influences offspring phenotype in either adverse or beneficial ways. We studied a
      well-established rat maternal protein-restriction model to determine whether post
      weaning dietary intervention improves adverse outcomes produced by a deficient
      maternal nutritional environment in pregnancy. Pregnant rats were fed a
      controlled diet (C, 20% casein) during pregnancy and lactation (CC) or were fed a
      restricted diet (R, 10% casein isocaloric diet) during pregnancy and C diet
      during lactation (RC). After weaning, the offspring were fed the C diet. At
      postnatal day (PND) 70 (young adulthood), female offspring either continued with
      the C diet (CCC and RCC) or were fed commercial Chow Purina 5001 (I) to further
      divide the animals into dietary intervention groups CCI and RCI. Another group of
      mothers and offspring were fed I throughout (III). Offspring food intake was
      averaged between PND 95-110 and 235-250 and carcass and liver compositions were
      measured at PND 25 and 250. Leptin (PND 110 and 250) and serum glucose,
      triglycerides and cholesterol (PND 250) levels were measured. Statistical
      analysis was carried out using ANOVA. At PND 25, body and liver weights were
      similar between groups; however, CCC and RCC carcass protein:fat ratios were
      lower compared with III diet. At PND 110 and 250, offspring CCC and RCC had
      higher body weight, food intake and serum leptin compared with CCI and RCI. CCI
      had lower carcass fat and increased protein compared with CCC and improved
      fasting glucose and triglycerides. Adult dietary intervention partially overcomes
      adverse effects of programming. Further studies are needed to determine the
      mechanisms involved. 

PMID- 25857641
TI  - Germline and somatic mutations in meningiomas.
AB  - Meningiomas arise from the arachnoid layer of the meninges that surround the
      brain and spine. They account for over one third of all primary central nervous
      system tumors in adults and confer a significant risk of location-dependent
      morbidity due to compression or displacement. A significant increase in risk of
      meningiomas is associated with neurofibromatosis type 2 (NF2) disease through
      mutation of the NF2 gene. In addition, approximately 5% of individuals with
      schwannomatosis disease develop meningiomas, through mutation of the SWI/SNF
      chromatin remodeling complex subunit, SMARCB1. Recently, a second SWI/SNF complex
      subunit, SMARCE1, was identified as a cause of clear cell meningiomas, indicating
      a wider role for this complex in meningioma disease. The sonic hedgehog (SHH)
      GLI1 signaling pathway gene, SUFU, has also been identified as the cause of
      hereditary multiple meningiomas in a large Finnish family. The recent
      identification of somatic mutations in components of the SHH-GLI1 and AKT1-MTOR
      signaling pathways indicates the potential for cross talk of these pathways in
      the development of meningiomas. This review describes the known meningioma
      predisposition genes and their links to the recently identified somatic
      mutations. 

PMID- 25857642
TI  - The influence of polaron formation on exciton dissociation.
AB  - A linear tight-binding model was used to examine the yield of exciton
      dissociation under the influence of the electron-vibration interaction. The
      system consists of a linear chain, coupled to a single vibration, and electron
      vibration interaction is permitted to occur on certain sites. In the presence of
      this interaction, population tends to localize to build a polaron. The system
      loses polaron trapping energy to the environment through its coupling to the bath
      environment, and loses population due to the injection into the electrode at the
      terminal site. A self-energy term was generated from population injection, and
      was added to the energy level of the last site, working as a sink function to
      absorb the electrons and measure the yield. This injection occurs only when the
      electron energy is inside and around the band. When the electron energy is
      outside the tight-binding band, population injection is inhibited. Our aim is to
      investigate the exciton dissociation effected by the competition between polaron
      formation and population injection, via a process strongly influenced by the
      inter-site coupling and the electron-vibration interaction. 

PMID- 25857643
TI  - Battling Against Interfaith Relations in Israel: Religion, Therapy, and Social
      Services.
AB  - One of the less studied aspects of the Israeli-Palestinian conflict is its
      demography. On the Jewish side, active steps are taken by the state to encourage
      Jewish immigration and Jewish births and discourage Jewish assimilation. As part
      of these efforts, the "problematic relationships" between Arab men and Jewish
      women from low socioeconomic background have become a high agenda item in public
      discussions in Israel during the last decade. I will examine here how the
      diagnostic category "girls at risk" and a therapeutic intervention employed by
      social services dealing with these couples helps maintaining the delicate balance
      between Jewish and democratic values. I will analyze these practices as a
      solution to a structural problem of the Jewish enclave in Israel.

PMID- 25857645
TI  - Sex differences associated with hepatitis B virus surface antigen seropositivity
      unwareness in hepatitis B virus surface antigen-positive adults: 2007-2012 Korea
      National Health and Nutrition Examination Survey.
AB  - OBJECTIVES: To examine the sex-specific factors associated with being unaware of
      one's hepatitis B virus surface antigen (HBsAg) seropositivity status in a large,
      HBsAg-positive population of Koreans. METHODS: In total, 1197 subjects aged 19
      years or older who were HBsAg-positive according to data from the 2007-2012 Korea
      National Health and Nutrition Examination Survey were included. Subjects were
      considered unaware of their HBsAg seropositivity status if they answered that
      they had no knowledge of being previously infected by the hepatitis B virus (HBV)
      or diagnosed with HBV hepatitis. Multivariate Poisson regression models with
      robust variance estimate were used to assess the significance of the variables
      using weighted frequencies. RESULTS: The majority (77.8%) of HbsAg-positive
      Korean adults (females, 81.9%; males, 74.6%) were unaware of their HBsAg
      seropositivity status. We found that sex (female: prevalence ratio [PR] 1.19),
      household income (low: PR, 1.15), marital status (never married: PR, 1.18), self
      rated health (moderate: PR, 1.14; good: PR, 1.12), and alcohol use (at least 2-3
      times/wk: PR, 1.21) were associated with being unaware. In females, age (50 to 59
      years: PR, 1.29; >= 70 years: PR, 1.30), household income (low: PR, 1.37; middle
      low: PR, 1.24), and marital status (never married: PR, 1.33) were associated with
      being unaware. In males, self-rated health (moderate: PR, 1.14; good: PR, 1.21)
      and alcohol use (at least 2-3 times/wk: PR, 1.21) were associated with being
      unaware. CONCLUSIONS: Factors related to the socioeconomic status of females and
      the health-related behaviors of males were found to be associated with being
      unaware of one's HBsAg seropositivity status.

PMID- 25857646
TI  - Socioeconomic disparities in osteoporosis prevalence: different results in the
      overall Korean adult population and single-person households.
AB  - OBJECTIVES: The present study was conducted in order to examine the association
      between socioeconomic status (SES) and osteoporosis prevalence in Korea and to
      assess whether different associations are found in single-person households.
      METHODS: A cross-sectional population-based study was conducted using the Korea
      National Health and Nutrition Examination Survey, from 2008 to 2011. The study
      subjects were people aged >= 50 years with osteoporosis as defined by bone
      mineral density. Multivariate logistic models were used to estimate prevalence
      odds ratios (pORs) and 95% confidence intervals (CIs). Gender differences in the
      likelihood of osteoporosis were analyzed based on household income, education
      level, and residential area. RESULTS: There were 8221 osteoporosis patients aged
      >= 50 years, of whom 927 lived in single-person households. There was a gender
      specific association between osteoporosis prevalence and all three SES factors
      that we analyzed: income, education, and residential area. After adjusting for
      age, SES, and health behaviors, including body mass index (BMI), low household
      income was only significantly associated with osteoporosis in men, whereas
      education level had an inverse relationship with osteoporosis only in women (p =
      0.01, p < 0.001, respectively). However, after controlling for age and BMI, rural
      residency was only associated with osteoporosis in women living in single-person
      households (pOR, 1.59; 95% CI, 1.05 to 2.43). CONCLUSIONS: The Korean adult
      population showed a gender-specific relationship between SES and osteoporosis
      prevalence, with a different pattern found in single-person households.

PMID- 25857648
TI  - Low systolic blood pressure and mortality from all causes and vascular diseases
      among older middle-aged men: Korean Veterans Health Study.
AB  - OBJECTIVES: Recently, low systolic blood pressure (SBP) was found to be
      associated with an increased risk of death from vascular diseases in a rural
      elderly population in Korea. However, evidence on the association between low SBP
      and vascular diseases is scarce. The aim of this study was to prospectively
      examine the association between low SBP and mortality from all causes and
      vascular diseases in older middle-aged Korean men. METHODS: From 2004 to 2010, 94
      085 Korean Vietnam War veterans were followed-up for deaths. The adjusted hazard
      ratios (aHR) were calculated using the Cox proportional hazard model. A
      stratified analysis was conducted by age at enrollment. SBP was self-reported by
      a postal survey in 2004. RESULTS: Among the participants aged 60 and older, the
      lowest SBP (<90 mmHg) category had an elevated aHR for mortality from all causes
      (aHR, 1.9; 95% confidence interval [CI], 1.2 to 3.1) and vascular diseases
      (International Classification of Disease, 10th revision, I00-I99; aHR, 3.2; 95%
      CI, 1.2 to 8.4) compared to those with an SBP of 100 to 119 mmHg. Those with an
      SBP below 80 mmHg (aHR, 4.5; 95% CI, 1.1 to 18.8) and those with an SBP of 80 to
      89 mmHg (aHR, 3.1; 95% CI, 0.9 to 10.2) also had an increased risk of vascular
      mortality, compared to those with an SBP of 90 to 119 mmHg. This association was
      sustained when excluding the first two years of follow-up or preexisting vascular
      diseases. In men younger than 60 years, the association of low SBP was weaker
      than that in those aged 60 years or older. CONCLUSIONS: Our findings suggest that
      low SBP (<90 mmHg) may increase vascular mortality in Korean men aged 60 years or
      older.

PMID- 25857647
TI  - The combined effect of subjective body image and body mass index (distorted body
      weight perception) on suicidal ideation.
AB  - OBJECTIVES: Mental health disorders and suicide are an important and growing
      public health concern in Korea. Evidence has shown that both globally and in
      Korea, obesity is associated with an increased risk of developing some
      psychiatric disorders. Therefore, we examined the association between distorted
      body weight perception (BWP) and suicidal ideation. METHODS: Data were obtained
      from the 2007-2012 Korea National Health and Nutritional Evaluation Survey
      (KNHANES), an annual cross-sectional nationwide survey that included 14 276 men
      and 19 428 women. Multiple logistic regression analyses were conducted to
      investigate the associations between nine BWP categories, which combined body
      image (BI) and body mass index (BMI) categories, and suicidal ideation. Moreover,
      the fitness of our models was verified using the Akaike information criterion.
      RESULTS: Consistent with previous studies, suicidal ideation was associated with
      marital status, household income, education level, and perceived health status in
      both genders. Only women were significantly more likely to have distorted BWP;
      there was no relationship among men. In category B1 (low BMI and normal BI),
      women (odds ratio [OR], 2.25; 95% confidence interval [CI], 1.48 to 3.42) were
      more likely to express suicidal ideation than women in category B2 (normal BMI
      and normal BI) were. Women in overweight BWP category C2 (normal BMI and fat BI)
      also had an increased OR for suicidal ideation (OR, 2.25; 95% CI, 1.48 to 3.42).
      Those in normal BWP categories were not likely to have suicidal ideation. Among
      women in the underweight BWP categories, only the OR for those in category A2
      (normal BMI and thin BI) was significant (OR, 1.34; 95% CI, 1.13 to 1.59).
      CONCLUSIONS: Distorted BWP should be considered an important factor in the
      prevention of suicide and for the improvement of mental health among Korean
      adults, especially Korean women with distorted BWPs.

PMID- 25857649
TI  - Influence of asthma on the longitudinal trajectories of cigarette use behaviors
      from adolescence to adulthood using latent growth curve models.
AB  - OBJECTIVES: While epidemiologic research indicates that the prevalence of risk
      taking behaviors including cigarette smoking among young people with asthma is
      substantial, the longitudinal patterns of cigarette smoking in this vulnerable
      population have received little attention. The aim of this study was to evaluate
      differences in the longitudinal trajectories of cigarette use behaviors from
      adolescence to adulthood between young people with and without asthma. METHODS:
      Data from the National Longitudinal Study of Adolescent to Adult Health (Add
      Health) during the years 1994 to 1995 (Wave I, adolescence), 2001 to 2002 (Wave
      III, young adulthood), and 2007 to 2008 (Wave IV, adulthood) were analyzed (n=12
      244). Latent growth curve models were used to examine the longitudinal
      trajectories of cigarette use behaviors during the transition to adulthood
      according to asthma status. RESULTS: Regardless of asthma status, the trajectory
      means of cigarette use behaviors were found to increase, and then slightly
      decrease from adolescence to adulthood. In total participants, there were no
      statistically significant differences in initial levels and changes in cigarette
      use behaviors according to asthma status. However, in select sex and race
      subgroups (i.e., females and non-whites), former asthmatics showed greater
      escalation in cigarette use behaviors than did non-asthmatics or current
      asthmatics. CONCLUSIONS: This study indicated that the changing patterns of
      cigarette use behaviors during the transition to adulthood among young people
      with asthma are comparable to or even more drastic than those among young people
      without asthma.

PMID- 25857650
TI  - Long distance spin communication in chemical vapour deposited graphene.
AB  - Graphene is an ideal medium for long-distance spin communication in future
      spintronic technologies. So far, the prospect is limited by the smaller sizes of
      exfoliated graphene flakes and lower spin transport properties of large-area
      chemical vapour-deposited (CVD) graphene. Here we demonstrate a high spintronic
      performance in CVD graphene on SiO2/Si substrate at room temperature. We show
      pure spin transport and precession over long channel lengths extending up to 16
      MUm with a spin lifetime of 1.2 ns and a spin diffusion length ~6 MUm at room
      temperature. These spin parameters are up to six times higher than previous
      reports and highest at room temperature for any form of pristine graphene on
      industrial standard SiO2/Si substrates. Our detailed investigation reinforces the
      observed performance in CVD graphene over wafer scale and opens up new prospects
      for the development of lateral spin-based memory and logic applications. 

PMID- 25857651
TI  - Criteria for Quick and Consistent Synthesis of Poly(glycerol sebacate) for
      Tailored Mechanical Properties.
AB  - Poly(glycerol sebacate) (PGS) and its derivatives make up an attractive class of
      biomaterial owing to their tunable mechanical properties with programmable
      biodegradability. In practice, however, the application of PGS is often hampered
      by frequent inconsistency in reproducing process conditions. The inconsistency
      stems from the volatile nature of glycerol during the esterification process. In
      this study, we suggest that the degree of esterification (DE) can be used to
      predict precisely the physical status, the mechanical properties, and the
      degradation of the PGS materials. Young's modulus is shown to linearly increase
      with DE, which is in agreement with an entropic spring theory of rubbers. To
      provide a processing guideline for researchers, we also provide a physical status
      map as a function of curing temperature and time. The amount of glycerol loss,
      obtainable by monitoring the evolution of the total mass loss and the DE during
      synthesis, is shown to make the predictions even more precise. We expect that
      these strategies can be applicable to different categories of polymers that
      involve condensation polymerization with the volatility of the reactants. In
      addition, we demonstrate that microwave-assisted prepolymerization is a time- and
      energy-efficient pathway to obtain PGS. For example, 15 min of microwave time is
      shown to be as efficient as prepolymerization in nitrogen atmosphere for 6 h at
      130  degrees C. The quick synthesis method, however, causes a severe evaporation
      of glycerol, resulting in a large distortion in the monomer ratio between
      glycerol and sebacic acid. Consequently, more rigid PGS is produced under a
      similar curing condition compared to the conventional prepolymerization method.
      Finally, we demonstrate that the addition of molecularly rigid cross-linking
      agents and network-structured inorganic nanoparticles are also effective in
      enhancing the mechanical properties of the PGS-derived materials. 

PMID- 25857652
TI  - Validating the measurement of social capital in Bangladesh: a cognitive approach.
AB  - Despite the growing evidence linking social capital to improvements in health and
      health behaviors, reliable measures of social capital are lacking in low-income
      countries. To accurately measure social capital in new contexts, there is a need
      to validate social capital survey questions in each new cultural setting. In this
      article, we examine the content validity of the measurement of social capital in
      Bangladesh using qualitative methods. In December 2012, we conducted four focus
      group discussions and 32 cognitive interviews in one rural subdistrict (Durgapur)
      and one urban slum (Mirpur). We used the findings from the focus groups and
      cognitive interviews to create a new social capital survey instrument that can be
      used by health and development organizations in Bangladesh. Furthermore, in this
      article, we provide insight into social capital survey research in general,
      including suggestions for the measurement of group membership, social support,
      collective action, and social trust. 

PMID- 25857654
TI  - "There Are No Known Benefits . . .": Considering the Risk/Benefit Ratio of
      Qualitative Research.
AB  - Institutional review boards (IRBs) are responsible for weighing the risks and
      benefits of research participation. Qualitative researchers note numerous
      instances where IRB ethical frameworks fail to align with the ethics of their
      research projects and point out that IRB understandings of the benefits and risks
      of research often differ from those of the participants they seek to protect.
      This qualitative cross-case research investigates participants' interview
      experiences in six qualitative studies that differed in their methods, subject of
      focus, and populations. Our findings indicate that contemporary IRBs' use of
      population "vulnerability" and topic "sensitivity" to assess project risk does
      not adequately determine the benefits, risks, or ethicality of research. We
      recommend that IRBs treat as real the evidence for benefits in qualitative
      research, recognize that sensitivity and vulnerability do not predict risk, and
      encourage researchers to attend to relationships in their projects.

PMID- 25857653
TI  - Exploring important influences on the healthfulness of prostate cancer survivors'
      diets.
AB  - A cancer diagnosis is often conceptualized as a teachable moment when individuals
      might be motivated to make lifestyle changes. Many prostate cancer survivors,
      however, do not adhere to dietary guidelines. In this article, we explore how
      cancer affected prostate cancer survivors' diets and identify important
      influences on diet. Twenty prostate cancer survivors completed three 24-hour
      dietary recalls and an in-depth dietary interview. We analyzed interviews using a
      constant comparison approach, and dietary recall data quantitatively to assess
      quality and qualitatively to identify food choice patterns. Most men reported not
      making dietary changes following their cancer diagnosis but did express an
      interest in healthy eating, primarily to facilitate weight loss. Men portrayed
      barriers to healthy eating that often outweighed their motivation to eat healthy.
      Public health programs should consider alternative ways of framing healthy eating
      programs for prostate cancer survivors that might be more effective than a cancer
      specific focus. 

PMID- 25857655
TI  - From themes to hypotheses: following up with quantitative methods.
AB  - One important category of mixed-methods research designs consists of quantitative
      studies that follow up on qualitative research. In this case, the themes that
      serve as the results from the qualitative methods generate hypotheses for testing
      through the quantitative methods. That process requires operationalization to
      translate the concepts from the qualitative themes into quantitative variables.
      This article illustrates these procedures with examples that range from simple
      operationalization to the evaluation of complex models. It concludes with an
      argument for not only following up qualitative work with quantitative studies but
      also the reverse, and doing so by going beyond integrating methods within single
      projects to include broader mutual attention from qualitative and quantitative
      researchers who work in the same field. 

PMID- 25857656
TI  - Direct Aqueous Self-Assembly of an Amphiphilic Diblock Copolymer toward
      Multistimuli-Responsive Fluorescent Anisotropic Micelles.
AB  - It is extremely important for emerging applications and still enormously
      challenging to develop multifunctional stimuli-responsive anisotropic polymeric
      micelles with integration of potentially targeted therapeutic and diagnostic
      function. Herein, we report a first example of fluorescent anisotropic micelles
      (FAMs) with Fe(3+), DTT, H2O2, and thermal responsive fluorescence and
      morphology. FAMs from direct aqueous self-assembly of amphiphilic diblock
      copolymer showed reversible "switch off/on" of aqua fluorescent emission and
      controllable structural change by sequential addition of Fe(3+) and DTT. In
      addition, the FAMs had reversible dual-thermal responsiveness of fluorescence and
      morphology. This micelle could serve as a promising candidate for all-in-one
      application of quantitative detecting, imaging, drug delivery, and targeted
      release. 

PMID- 25857657
TI  - Bell's palsy: aetiology, clinical features and multidisciplinary care.
AB  - Bell's palsy is a common cranial neuropathy causing acute unilateral lower motor
      neuron facial paralysis. Immune, infective and ischaemic mechanisms are all
      potential contributors to the development of Bell's palsy, but the precise cause
      remains unclear. Advancements in the understanding of intra-axonal signal
      molecules and the molecular mechanisms underpinning Wallerian degeneration may
      further delineate its pathogenesis along with in vitro studies of virus-axon
      interactions. Recently published guidelines for the acute treatment of Bell's
      palsy advocate for steroid monotherapy, although controversy exists over whether
      combined corticosteroids and antivirals may possibly have a beneficial role in
      select cases of severe Bell's palsy. For those with longstanding sequaelae from
      incomplete recovery, aesthetic, functional (nasal patency, eye closure, speech
      and swallowing) and psychological considerations need to be addressed by the
      treating team. Increasingly, multidisciplinary collaboration between interested
      clinicians from a wide variety of subspecialties has proven effective. A patient
      centred approach utilising physiotherapy, targeted botulinum toxin injection and
      selective surgical intervention has reduced the burden of long-term disability in
      facial palsy. 

PMID- 25857658
TI  - The corpus callosum in the diagnosis of multiple sclerosis and other CNS
      demyelinating and inflammatory diseases.
AB  - Lesions in the corpus callosum (CC) are important radiological clues to the
      diagnosis of multiple sclerosis (MS), but may also occur in other
      neuroinflammatory and non-neuroinflammatory conditions. In this article, we
      discuss the radiological features of lesions within the CC in MS and other
      central nervous system inflammatory and acquired demyelinating diseases. An
      understanding of the appearance and location of lesions in the CC is important
      not only for accurate diagnosis and treatment of these various conditions, but as
      it also provides insights into pathogenesis. 

PMID- 25857659
TI  - Identifying who will benefit from non-invasive ventilation in amyotrophic lateral
      sclerosis/motor neurone disease in a clinical cohort.
AB  - BACKGROUND: Respiratory failure is associated with significant morbidity and is
      the predominant cause of death in motor neurone disease/amyotrophic lateral
      sclerosis (MND/ALS). This study aimed to determine the effect of non-invasive
      ventilatory (NIV) support on survival and pulmonary function decline across
      MND/ALS phenotypes. METHODS: Cohort recruited via a specialist, multidisciplinary
      clinic. Patients were categorised into four clinical phenotypes (ALS, flail arm,
      flail leg and primary lateral sclerosis) according to site of presenting symptom
      and the pattern of upper versus lower motor neurone involvement. NIV was
      initiated according to current consensus practice guidelines. RESULTS: Between
      1991 and 2011, 1198 patients diagnosed with ALS/MND were registered. 929 patients
      (77.5%) fulfilled the selection criteria and their data were analysed. Median
      tracheostomy free survival from symptom onset was 28 months in NIV-treated
      patients compared to 15 months in untreated (Univariate Cox regression HR=0.61
      (0.51 to 0.73), p<0.001). The positive survival effect of NIV persisted when the
      model was adjusted for age, gender, riluzole and percutaneous endoscopic
      gastrostomy use (HR=0.72 (0.60 to 0.88, p=0.001). In contrast with the only
      randomised controlled trial, NIV statistically significantly increased survival
      by 19 months in those with ALS-bulbar onset (Univariate HR=0.50 (0.36 to 0.70),
      multivariate HR=0.59 (0.41 to 0.83)). These data confirm that NIV improves
      survival in MND/ALS. The overall magnitude of benefit is 13 months and was
      largest in those with ALS-bulbar disease. Future research should explore the
      optimal timing of NIV initiation within phenotypes in order to optimise
      respiratory function, quality of life and survival.

PMID- 25857660
TI  - The correlation between the change of distal motor latency of the median nerve
      and the abundant A-waves in Guillain-Barre syndrome.

PMID- 25857661
TI  - Seropositivity for NT5c1A antibody in sporadic inclusion body myositis predicts
      more severe motor, bulbar and respiratory involvement.
AB  - OBJECTIVES: To explore phenotypic differences between individuals with sporadic
      inclusion body myositis (sIBM) who are seropositive for the NT5c1A antibody
      compared with those who are seronegative. METHODS: Cross-sectional clinical,
      serological and functional analysis in 25 consecutive participants with sIBM.
      RESULTS: All participants met criteria for clinically defined or probable sIBM.
      18 of 25 participants with sIBM (72%) were seropositive for the NT5c1A antibody.
      No differences between median age and duration of illness between the two groups
      were seen. Females have higher odds of being seropositive (OR=2.30). Participants
      with seropositive sIBM took significantly longer to get up and stand (p=0.012).
      There were no significant differences between the two groups in terms of distance
      covered on a 6 min walk. Seropositive participants were more likely to require
      assistive devices such as a walker or wheelchair for mobility (OR=23.00;
      p=0.007). A number of secondary (exploratory) outcomes were assessed. NT5c1A
      seropositive sIBM cases had lower total Medical Research Council (MRC) sum score
      and MRC sum score on the right (p=0.03 and 0.02, respectively). Participants with
      the NT5c1A antibody were significantly more likely to have symptoms of dysphagia
      (OR=10.67; p=0.03) and reduced forced vital capacity (p=0.005). Facial weakness
      occurred in 50% of seropositive participants while it was only seen in 14% of
      seronegative participants. CONCLUSIONS: Even though the small sample size limits
      definite conclusions, our cross-sectional study showed seropositivity to the
      NT5c1A antibody is associated with greater motor and functional disability in
      sIBM. The study also suggests more prominent bulbar, facial and respiratory
      involvement in individuals positive for NT5c1A antibodies.

PMID- 25857662
TI  - Immune-mediated mechanisms influencing the efficacy of anticancer therapies.
AB  - Conventional anticancer therapies, such as chemotherapy, radiotherapy, and
      targeted therapy, are designed to kill cancer cells. However, the efficacy of
      anticancer therapies is not only determined by their direct effects on cancer
      cells but also by off-target effects within the host immune system. Cytotoxic
      treatment regimens elicit several changes in immune-related parameters including
      the composition, phenotype, and function of immune cells. Here we discuss the
      impact of innate and adaptive immune cells on the success of anticancer therapy.
      In this context we examine the opportunities to exploit host immune responses to
      boost tumor clearing, and highlight the challenges facing the treatment of
      advanced metastatic disease. 

PMID- 25857663
TI  - The recently identified modifier of murine metastable epialleles, Rearranged L
      Myc Fusion, is involved in maintaining epigenetic marks at CpG island shores and
      enhancers.
AB  - BACKGROUND: We recently identified a novel protein, Rearranged L-myc fusion
      (Rlf), that is required for DNA hypomethylation and transcriptional activity at
      two specific regions of the genome known to be sensitive to epigenetic gene
      silencing. To identify other loci affected by the absence of Rlf, we have now
      analysed 12 whole genome bisulphite sequencing datasets across three different
      embryonic tissues/stages from mice wild-type or null for Rlf. RESULTS: Here we
      show that the absence of Rlf results in an increase in DNA methylation at
      thousands of elements involved in transcriptional regulation and many of the
      changes occur at enhancers and CpG island shores. ChIP-seq for H3K4me1, a mark
      generally found at regulatory elements, revealed associated changes at many of
      the regions that are differentially methylated in the Rlf mutants. RNA-seq showed
      that the numerous effects of the absence of Rlf on the epigenome are associated
      with relatively subtle effects on the mRNA population. In vitro studies suggest
      that Rlf's zinc fingers have the capacity to bind DNA and that the protein
      interacts with other known epigenetic modifiers. CONCLUSION: This study provides
      the first evidence that the epigenetic modifier Rlf is involved in the
      maintenance of DNA methylation at enhancers and CGI shores across the genome.

PMID- 25857664
TI  - Bottlenecks in carotenoid biosynthesis and accumulation in rice endosperm are
      influenced by the precursor-product balance.
AB  - The profile of secondary metabolites in plants reflects the balance of
      biosynthesis, degradation and storage, including the availability of precursors
      and products that affect the metabolic equilibrium. We investigated the impact of
      the precursor-product balance on the carotenoid pathway in the endosperm of
      intact rice plants because this tissue does not normally accumulate carotenoids,
      allowing us to control each component of the pathway. We generated transgenic
      plants expressing the maize phytoene synthase gene (ZmPSY1) and the bacterial
      phytoene desaturase gene (PaCRTI), which are sufficient to produce beta-carotene
      in the presence of endogenous lycopene beta-cyclase. We combined this mini
      pathway with the Arabidopsis thaliana genes AtDXS (encoding 1-deoxy-D-xylulose 5
      phosphate synthase, which supplies metabolic precursors) or AtOR (the ORANGE
      gene, which promotes the formation of a metabolic sink). Analysis of the
      resulting transgenic plants suggested that the supply of isoprenoid precursors
      from the MEP pathway is one of the key factors limiting carotenoid accumulation
      in the endosperm and that the overexpression of AtOR increased the accumulation
      of carotenoids in part by up-regulating a series of endogenous carotenogenic
      genes. The identification of metabolic bottlenecks in the pathway will help to
      refine strategies for the creation of engineered plants with specific carotenoid
      profiles. 

PMID- 25857665
TI  - Fecal Microbiota Transplantation Induces Remission in Patients With Active
      Ulcerative Colitis in a Randomized Controlled Trial.
AB  - BACKGROUND & AIMS: Ulcerative colitis (UC) is difficult to treat, and standard
      therapy does not always induce remission. Fecal microbiota transplantation (FMT)
      is an alternative approach that induced remission in small series of patients
      with active UC. We investigated its safety and efficacy in a placebo-controlled
      randomized trial. METHODS: We performed a parallel study of patients with active
      UC without infectious diarrhea. Participants were examined by flexible
      sigmoidoscopy when the study began and then were randomly assigned to groups that
      received FMT (50 mL, via enema, from healthy anonymous donors; n = 38) or placebo
      (50 mL water enema; n = 37) once weekly for 6 weeks. Patients, clinicians, and
      investigators were blinded to the groups. The primary outcome was remission of
      UC, defined as a Mayo score <=2 with an endoscopic Mayo score of 0, at week 7.
      Patients provided stool samples when the study began and during each week of FMT
      for microbiome analysis. The trial was stopped early for futility by the Data
      Monitoring and Safety Committee, but all patients already enrolled in the trial
      were allowed to complete the study. RESULTS: Seventy patients completed the trial
      (3 dropped out from the placebo group and 2 from the FMT group). Nine patients
      who received FMT (24%) and 2 who received placebo (5%) were in remission at 7
      weeks (a statistically significant difference in risk of 17%; 95% confidence
      interval, 2%-33%). There was no significant difference in adverse events between
      groups. Seven of the 9 patients in remission after FMT received fecal material
      from a single donor. Three of the 4 patients with UC <=1 year entered remission,
      compared with 6 of 34 of those with UC >1 year (P = .04, Fisher's exact test).
      Stool from patients receiving FMT had greater microbial diversity, compared with
      baseline, than that of patients given the placebo (P = .02, Mann-Whitney U test).
      CONCLUSIONS: FMT induces remission in a significantly greater percentage of
      patients with active UC than placebo, with no difference in adverse events. Fecal
      donor and time of UC appear to affect outcomes. ClinicalTrials.gov Number:
      NCT01545908.

PMID- 25857667
TI  - Effects of 92% oxygen administration on cognitive performance and physiological
      changes of intellectually and developmentally disabled people.
AB  - BACKGROUND: The present study addressed how 92% oxygen administration affects
      cognitive performance, blood oxygen saturation (SpO2), and heart rate (HR) of
      intellectually and developmentally disabled people. METHODS: Seven males (28.9 +/
      1.8 years) and seven females (34.4 +/- 8.3 years) with intellectual and
      developmental disabilities (disabled level 2.1 +/- 0.5) completed an experiment
      consisting a 0-back task with normal air (21% oxygen) administered in one run and
      hyperoxic air (92% oxygen) administered in the other run. The experimental
      sequence in each run consisted of a 1-min adaptation phase, 2-min control phase,
      and 2-min 0-back task phase, where SpO2 and HR were gauged for each phase.
      RESULTS: The administration of 92% oxygen increased 0-back task performance of
      intellectually and developmentally disabled people, in association with increased
      SpO2 and decreased HR. Our results demonstrate that sufficient oxygen supply
      subserving cognitive functions, even as a short-term effect, could increase
      cognitive ability for the intellectually and developmentally disabled people.
      CONCLUSIONS: It is concluded that enriched oxygen can positively affect, at least
      in the short-term, the working memory of those with intellectual and
      developmental disability.

PMID- 25857666
TI  - Multi-cellular 3D human primary liver cell culture elevates metabolic activity
      under fluidic flow.
AB  - We have developed a low-cost liver cell culture device that creates fluidic flow
      over a 3D primary liver cell culture that consists of multiple liver cell types,
      including hepatocytes and non-parenchymal cells (fibroblasts, stellate cells, and
      Kupffer cells). We tested the performance of the cell culture under fluidic flow
      for 14 days, finding that hepatocytes produced albumin and urea at elevated
      levels compared to static cultures. Hepatocytes also responded with induction of
      P450 (CYP1A1 and CYP3A4) enzyme activity when challenged with P450 inducers,
      although we did not find significant differences between static and fluidic
      cultures. Non-parenchymal cells were similarly responsive, producing interleukin
      8 (IL-8) when challenged with 10 MUM bacterial lipoprotein (LPS). To create the
      fluidic flow in an inexpensive manner, we used a rocking platform that tilts the
      cell culture devices at angles between +/-12 degrees , resulting in a
      periodically changing hydrostatic pressure drop between reservoirs and the
      accompanying periodically changing fluidic flow (average flow rate of 650 MUL
      min(-1), and a maximum shear stress of 0.64 dyne cm(-2)). The increase in
      metabolic activity is consistent with the hypothesis that, similar to
      unidirectional fluidic flow, primary liver cell cultures increase their metabolic
      activity in response to fluidic flow periodically changes direction. Since
      fluidic flow that changes direction periodically drastically changes the behavior
      of other cells types that are shear sensitive, our findings support the theory
      that the increase in hepatic metabolic activity associated with fluidic flow is
      either activated by mechanisms other than shear sensing (for example increased
      opportunities for gas and metabolite exchange), or that it follows a shear
      sensing mechanism that does not depend on the direction of shear. Our mode of
      device operation allows us to evaluate drugs under fluidic cell culture
      conditions and at low device manufacturing and operation costs. 

PMID- 25857668
TI  - Implantation of a total abdominal mesh plastic ending up in multiple, lethal
      right heart injuries.
AB  - We present the case of a 62-year old patient who had an elective surgery to
      implant a total abdominal plastic mesh due to massive herniation after prior
      lower body gun shots and deep wound infections. Twenty-four hours after the
      operation, the patient's condition deteriorated, ST-deviation occurred and the
      Troponin I test was positive. On admission, the patient needed moderate
      catecholamine therapy and echocardiography showed a pericardial effusion (>3 cm).
      Puncture of the effusion was impossible due to the plastic mesh and the patient
      was transferred to the operating room. A subxiphoidal pericardial incision was
      performed and 800 ml of fresh blood was drained. Despite this, the patient's
      condition worsened. A full sternotomy was performed, and intrathoracal
      cardiopulmonary resuscitation started. During examination of the pericardium and
      the heart, multiple plastic parts from the mesh fixation system were observed
      transdiaphragmally and were found to have penetrated the diaphragmal part of the
      right ventricle. In spite of maximum drug, respiratory and surgical therapy, a
      sufficient heart ejection fraction could not be achieved. Upon interdisciplinary
      consent, therapy was stopped after 60 min. 

PMID- 25857669
TI  - GS-align for glycan structure alignment and similarity measurement.
AB  - MOTIVATION: Glycans play critical roles in many biological processes, and their
      structural diversity is key for specific protein-glycan recognition. Comparative
      structural studies of biological molecules provide useful insight into their
      biological relationships. However, most computational tools are designed for
      protein structure, and despite their importance, there is no currently available
      tool for comparing glycan structures in a sequence order- and size-independent
      manner. RESULTS: A novel method, GS-align, is developed for glycan structure
      alignment and similarity measurement. GS-align generates possible alignments
      between two glycan structures through iterative maximum clique search and
      fragment superposition. The optimal alignment is then determined by the maximum
      structural similarity score, GS-score, which is size-independent. Benchmark tests
      against the Protein Data Bank (PDB) N-linked glycan library and PDB
      homologous/non-homologous N-glycoprotein sets indicate that GS-align is a robust
      computational tool to align glycan structures and quantify their structural
      similarity. GS-align is also applied to template-based glycan structure
      prediction and monosaccharide substitution matrix generation to illustrate its
      utility. AVAILABILITY AND IMPLEMENTATION: http://www.glycanstructure.org/gsalign.
      CONTACT: wonpil@ku.edu SUPPLEMENTARY INFORMATION: Supplementary data are
      available at Bioinformatics online.

PMID- 25857670
TI  - The roles of excision repair cross-complementation group1 in objective response
      after cisplatin-based concurrent chemoradiotherapy and survival in head and neck
      cancers: a systematic review and meta-analysis.
AB  - Our aim of the study was to investigate the precise relationship of repair cross
      complementation group 1 (ERCC1) expression and the survival as well as objective
      response rate to cisplatin-based concurrent chemoradiotherapy (CCRT) and a meta
      analysis was conducted to analysis ERCC1's prognostic roles in head and neck
      cancer. A search based on published articles in PubMed, Embase and CKNI database
      (up to Oct 15, 2014) to find eligible studies meeting eligibility criteria and
      then a meta-analysis was conducted to assess the outcomes in head and neck
      squamous cell carcinomas (HNSCC) patients with different ERCC1 expression. The
      principle outcomes were hazard ratio (HR) for survival analysis and relative
      risks (RR) for objective response. Fixed or random model was used for calculation
      according to the heterogeneity. The results showed that 9 studies involving 568
      patients met the inclusion criteria. Low/negative expression of ERCC1 was
      associated with longer overall survival (OS) and profession-free survival (PFS)
      after receiving cisplatin-based CCRT therapy (HR 0.38; 95% confidence interval
      (CI) 0.21-0.63; P<0.001 and HR 0.37; 95%CI 0.21-0.63; P<0.001). And there was no
      significant difference discovered in objective response rate between low/negative
      and high/positive ERCC1 expression (RR 1.19; 95%CI 1.00-1.43; P=0.06). Evidence
      of modest heterogeneity was found between ERCC1 expression and OS (I(2)=48.8%,
      P<0.05) and subgroup analysis was performed based on ethnicity, variable methods
      and primary tumor location. The conclusion is that ERCC1 might be the one of
      adverse prognostic factors affecting the survival time and objective response to
      cisplatin-based chemoradiotherap due to its drug-resistance characteristics.

PMID- 25857671
TI  - Predicting New-Onset Postoperative Atrial Fibrillation in Cardiac Surgery
      Patients.
AB  - OBJECTIVE: To derive a simple clinical prediction rule identifying patients at
      high risk of developing new-onset postoperative atrial fibrillation (POAF) after
      cardiac surgery. DESIGN: Retrospective analysis on prospectively collected
      observational data. SETTING: A university-affiliated cardiac hospital.
      PARTICIPANTS: Adult patients undergoing coronary artery bypass grafting and/or
      valve surgery. INTERVENTIONS: Observation for the occurrence of new-onset
      postoperative atrial fibrillation. MEASUREMENTS AND MAIN RESULTS: Details on 28
      preoperative variables from 999 patients were collected and significant
      predictors (p<0.2) were inserted into multivariable logistic regression and
      reconfirmed with recursive partitioning. A total of 305 (30.5%) patients
      developed new-onset POAF. Eleven variables were associated significantly with
      atrial fibrillation. A multivariable logistic regression model included left
      atrial dilatation, mitral valve disease, and age. Coefficients from the model
      were converted into a simple 7-point predictive score. The risk of POAF per score
      is: 15.0%, if 0; 20%, if 1; 27%, if 2; 35%, if 3; 44%, if 4; 53%, if 5; 62%, if
      6; and 70%, if 7. A score of 4 has a sensitivity of 44% and a specificity of 82%
      for POAF. A score of 6 has a sensitivity of 11% and a specificity of 97%.
      Bootstrapping with 5,000 samples confirmed the final model provided consistent
      predictions. CONCLUSIONS: This study proposed a simple predictive score
      incorporating three risk variables to identify cardiac surgical patients at high
      risk of developing new-onset POAF. Preventive treatment should target patients >=
      65 years with left atrial dilatation and mitral valve disease.

PMID- 25857672
TI  - Using Zero-Balance Ultrafiltration With Dialysate as a Replacement Solution for
      Toxin and Eptifibatide Removal on a Dialysis-Dependent Patient During
      Cardiopulmonary Bypass.

PMID- 25857673
TI  - Physiological responses related to moderate mental load during car driving in
      field conditions.
AB  - We measured physiological variables on nine car drivers to capture moderate
      magnitudes of mental load (ML) during driving in prolonged and repeated city and
      highway field conditions. Ecological validity was optimized by avoiding any
      artificial interference to manipulate drivers ML, drivers were alone in the car,
      they were free to choose their paths to the target, and the repeated drives
      familiarized drivers to the procedure. Our aim was to investigate if driver's
      physiological variables can be reliably measured and used as predictors of
      moderate individual levels of ML in naturally occurring unpredictably changing
      field conditions. Variables investigated were: heart-rate, skin conductance
      level, breath duration, blink frequency, blink duration, and eye fixation related
      potentials. After the drives, with support from video uptakes, a self-rating and
      a score made by external raters were used to distinguish moderately high and low
      ML segments. Variability was high but aggregated data could distinguish city from
      highway drives. Multivariate models could successfully classify high and low ML
      within highway and city drives using physiological variables as input. In
      summary, physiological variables have a potential to be used as indicators of
      moderate ML in unpredictably changing field conditions and to advance the
      evaluation and development of new active safety systems. 

PMID- 25857674
TI  - Extremism reduces conflict arousal and increases values affirmation in response
      to meaning violations.
AB  - In the social psychological threat-compensation literature, there is an apparent
      contradiction whereby relatively extreme beliefs both decrease markers of
      physiological arousal following meaning violations, and increase the values
      affirmation behaviors understood as a palliative responses to this arousal. We
      hypothesize that this is due to the differential impact of measuring extremism on
      behavioral inhibition and approach systems following meaning violations, whereby
      extremism both reduces markers of conflict arousal (BIS) and increases values
      affirmation (BAS) unrelated to this initial arousal. Using pupil dilation as a
      proxy for immediate conflict arousal, we found that the same meaning violation
      (anomalous playing cards) evoked greater pupil dilation, and that this pupillary
      reaction was diminished in participants who earlier reported extreme beliefs. We
      also found that reporting extreme beliefs was associated with greater affirmation
      of an unrelated meaning framework, where this affirmation was unrelated to
      physiological markers of conflict arousal. 

PMID- 25857675
TI  - Elements of informed consent and decision quality were poorly correlated in
      informed consent documents.
AB  - OBJECTIVES: Although informed consent (IC) documents must contain specific
      elements, inclusion of these elements may be insufficient to encourage high
      quality decision making. We assessed the extent to which documents conform to IC
      standards and how well conformity to decision quality (DQ) standards can be
      predicted by IC standards, IC document characteristics, and study
      characteristics. STUDY DESIGN AND SETTING: We obtained 139 IC documents for
      trials registered with ClinicalTrials.gov from study investigators. Using a four
      point scale, two raters independently assessed each IC document on 36 IC standard
      items and 9 DQ items. RESULTS: Overall agreement between raters across all 45
      items was 93%. Across the 36 IC standards items, conformity was generally quite
      high but variable, with 20 items showing conformity of 80% or more and seven
      items showing conformity of 50% or lower. IC standards concordance, overall
      length of the IC document, and country of study were all significant predictors
      of DQ standards but together accounted for less than 20% of the variance in DQ
      standards. CONCLUSION: Conformity to recommendations for improving IC documents
      was relatively high but variable. The extent to which an IC document conformed to
      these recommendations was only moderately related to whether it conformed to
      recommendations for improving DQ. Existing IC regulations may not describe the
      optimal approach to helping people make good study participation decisions.

PMID- 25857676
TI  - Adhesive contact of a rigid circular cylinder to a soft elastic substrate--the
      role of surface tension.
AB  - This article studies the effects of surface tension on the adhesive contact
      mechanics of a long rigid cylinder on an infinite half space comprising an
      incompressible elastic material. We present an exact solution based on small
      strain theory. The relationship between the indentation force and contact width
      was found to depend on a single dimensionless parameter omega =
      sigma/[4(MUR)(2/3)(W(ad)/2pi)(1/3'), where R is the cylinder radius, Wad is the
      interfacial work of adhesion, and sigma and MU are the surface tension and shear
      modulus of the half space, respectively. For small omega the solution reduces to
      the classical Johnson-Kendall-Roberts (JKR) theory, whereas for large omega the
      solution reduces to the small slope version of the Young-Dupre equation. The pull
      off phenomenon was carefully examined and it was found that the contact width at
      pull-off reduces to zero when surface tension is larger than a critical value.

PMID- 25857678
TI  - Occurrence, fate, removal and assessment of emerging contaminants in water in the
      water cycle (from wastewater to drinking water).

PMID- 25857677
TI  - Cardiovascular risk factor distribution and subjective risk estimation in urban
      women--the BEFRI study: a randomized cross-sectional study.
AB  - BACKGROUND: Awareness represents a major modulator for the uptake of preventive
      measures and healthy life-style choices. Women underestimate the role of
      cardiovascular diseases as causes of mortality, yet little information is
      available about their subjective risk awareness. METHODS: The Berlin Female Risk
      Evaluation (BEFRI) study included a randomized urban female sample aged 25-74
      years, in which 1,066 women completed standardized questionnaires and attended an
      extensive clinical examination. Subjective estimation was measured by a 3-point
      Likert scale question asking about subjective perception of absolute
      cardiovascular risk with a 10 year outlook to be matched to the cardiovascular
      risk estimate according to the Framingham score for women. RESULTS: An expected
      linear increase with age was observed for hypertension, hyperlipidemia, obesity,
      and vascular compliance measured by pulse pressure. Knowledge about optimal
      values of selected cardiovascular risk factor indicators increased with age, but
      not the perception of the importance of age itself. Only 41.35% of all the
      participants correctly classified their own cardiovascular risk, while 48.65%
      underestimated it, and age resulted as the most significant predictor for this
      subjective underestimation (OR = 3.5 for age >50 years compared to <50, 95% CI =
      2.6-4.8, P <0.0001). Therefore, although socioeconomic factors such as
      joblessness (OR = 1.9, 95% CI = 1.4-2.6, P <0.0001) and combinations of other
      social risk factors (low income, limited education, simple job, living alone,
      having children, statutory health coverage only; OR = 1.5, 95% CI = 1.1-2.1, P =
      0.009) also significantly influenced self-awareness, age appeared as the
      strongest predictor of risk underestimation and at the same time the least
      perceived cardiovascular risk factor. CONCLUSIONS: Less than half of the women in
      our study population correctly estimated their cardiovascular risk. The study
      identifies age as the strongest predictor of risk underestimation in urban women
      and at the same time as the least subjectively perceived cardiovascular risk
      factor. Although age itself cannot be modified, our data highlights the need for
      more explicit risk counseling and information campaigns about the cardiovascular
      relevance of aging while focusing on measures to control coexisting modifiable
      risk factors.

PMID- 25857679
TI  - Human Adipose Stem Cells Improve Mechanical Allodynia and Enhance Functional
      Recovery in a Rat Model of Neuropathic Pain.
AB  - Stem cells are a promising source of tissue engineering due to their
      differentiation potential. Today, direct transplantation of stem cells for cell
      therapy is commonly performed. However, in cases of nerve injury, direct
      transplantation of cells could lead to secondary nerve damage. Male Sprague
      Dawley rats were randomized into four groups: the phosphate-buffered saline
      epineural transplantation (PBS-ENT) group, the PBS intraneural transplantation
      (PBS-INT) group, the human adipose-derived stem cells epineural transplantation
      (hASCs-ENT) group, and human adipose-derived stem cells intraneural
      transplantation (hASCs-INT) group. Transplantation was conducted 1 week later
      after inflicting a crush injury with subsequent observation for 5 weeks. To
      evaluate pain, each group was examined with regard to paw withdrawal latency and
      evoked potentials. The sciatic functional index (SFI) was calculated to estimate
      functional recovery. The sciatic nerve was also examined histologically. The
      hASCs-ENT group showed a more rapid paw withdrawal threshold and SFI recovery
      than the other groups (p<0.05). The hASCs-ENT group also showed shorter initial
      latencies in both somatosensory evoked potential (SSEP) and motor evoked
      potential (MEP) than the PBS-INT group (p<0.05). In addition, the N1 latency of
      the MEP and the N1 and P1 latencies of the SSEP were significantly shorter than
      those of the PBS-INT group (p<0.05). Histological examination revealed that the
      transplanted groups showed better neural recovery and remyelination than the
      groups injected with PBS. These results show that the transplantation of hASCs
      into the injured sciatic nerve improved mechanical allodynia and functional
      recovery as determined by the paw withdrawal test, SFI analysis, and
      electrophysiological studies. ENT is superior to INT in terms of invasiveness and
      better outcomes.

PMID- 25857680
TI  - Incidence of Late-Stage Age-Related Macular Degeneration in American Whites:
      Systematic Review and Meta-analysis.
AB  - PURPOSE: To estimate incidence of age-related macular degeneration (AMD) by
      subtype in American whites aged >=50 years. DESIGN: Systematic review and meta
      analysis. METHODS:  SETTING: Prospective cohort studies of AMD incidence in
      populations of white European ancestry published in MEDLINE, EMBASE, and Web of
      Science. STUDY POPULATION: Fourteen publications in 10 populations that examined
      AMD incident cases were identified. OBSERVATION PROCEDURE: Data on age-sex
      specific incidence of late AMD, geographic atrophy (GA) and neovascular AMD
      (NVAMD), year of recruitment, AMD grading method, and continent were extracted.
      MAIN OUTCOME MEASURE(S): Annual incidence of late AMD, GA, and NVAMD by age-sex
      in American whites aged >=50 years from a Bayesian meta-analysis of incidence
      studies was compared with incidence extrapolated from published prevalence
      estimates. RESULTS: Incidence rates from the review agreed with those derived
      from prevalence, but the latter were based on more data, especially at older ages
      and by AMD subtypes. Annual incidence (estimated from prevalence) of late AMD in
      American whites was 3.5 per 1000 aged >=50 years (95% credible interval 2.5, 4.7
      per 1000), equivalent to 293 000 new cases in American whites per year (95%
      credible interval 207 000, 400 000). Incidence rates approximately quadrupled per
      decade in age. Annual incidence GA rates were 1.9 per 1000 aged >=50 years, NVAMD
      rates were 1.8 per 1000. Late AMD incidence was 38% higher in women vs men (95%
      credible interval 6%, 82%). CONCLUSIONS: Estimating AMD incidence from prevalence
      allows better characterization at older ages and by AMD subtype where
      longitudinal data from incidence studies are limited.

PMID- 25857681
TI  - Expression of Secreted Aspartyl Proteinases in an Experimental Model of Candida
      albicans-Associated Denture Stomatitis.
AB  - PURPOSE: Candida albicans is known to produce secreted aspartyl proteinases
      (SAPs) to aid adhesion, invasion, and host tissue destruction. SAPs may
      contribute to denture stomatitis (DS) pathogenesis. The aim of this study was to
      develop an in vivo experimental model for Candida-associated DS that allows the
      analysis of SAP2, SAP5, and SAP9 expression by C. albicans from biofilm induced
      on the denture surface. MATERIALS AND METHODS: Thirty-five male Wistar rats were
      divided into three groups: control, denture, and denture/Candida group. The last
      two groups remained with dentures for 2, 4, and 6 days, with or without induced
      biofilm. SAP expression was concomitant with leukocyte counts as well as clinical
      and histological changes shown by animal palate. RESULTS: The signs observed at 4
      days in the denture/Candida group were clinically closer to the Candida
      associated DS, showing a significant increase of neutrophils and decrease of
      lymphocytes in peripheral blood, presence of inflammation signs on the palate
      similar to DS Newton type I, and fungal invasion in the epithelial layer.
      Accordingly, the denture/Candida group at 4 days presented the highest relative
      expression of all SAPs studied. CONCLUSION: The results showed a coincidence
      between SAP expression and clinical, microscopic, and blood data. Finally, the
      molecular findings were consistent with the virulence capacities of C. albicans
      from biofilm formed on the denture resin, which possibly allowed epithelial
      invasion by the fungus.

PMID- 25857682
TI  - Employing photoacoustic spectroscopy in the evaluation of the skin permeation
      profile of emulsion containing antioxidant phenolic-rich extract of Melochia
      arenosa.
AB  - CONTEXT: Oxidative stress is an important factor modulating skin alterations.
      Melochia arenosa Benth. (Malvaceae) is a Brazilian plant with antimicrobial
      activity and antioxidant potential. OBJECTIVE: The objective of this study is to
      develop a topical formulation containing antioxidant phenolic-rich extract of M.
      arenosa and to evaluate its skin permeation profile. MATERIALS AND METHODS:
      Response surface methodology was used to maximize the total phenolic (TP) content
      of the extract and its antioxidant activity was evaluated by 2,2-diphenyl-1
      picryl-hydrazyl (DPPH), 2,2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid)
      (ABTS), and respiratory burst methods. An emulsion containing 1% optimized
      extract (OE) was developed and employed photoacoustic spectroscopy (PAS) for the
      determination of its skin permeation profile. The morphology of the skin was
      studied in histological sections stained with hematoxylin-eosin. RESULTS AND
      DISCUSSION: The optimum conditions predicted for the major extractive efficiency
      of the phenolics with 100% ethanol led extraction time 101 h and plant:solvent
      proportion 1:13.5 (w/v). OE presented TP = 724.6 +/- 8.2 mg GAE/g extract and
      scavenging capacity of DPPH (IC50 value = 11.43 +/- 0.14 ug/mL) and ABTS radicals
      (IC50 value = 35.42 +/- 0.48 ug/mL). The production of ROS by neutrophils after
      stimulation with phorbol miristate acetate was lower when the OE was present in
      the reaction medium, endorsing its high antioxidant capacity. The data obtained
      by PAS indicated that the OE present in the emulsion has permeated and was
      distributed in the whole skin. No histopathological alterations were observed in
      the histological analysis. CONCLUSION: The formulation developed is a promising
      tool for skin care and could prevent the damage caused by oxidative stress.

PMID- 25857683
TI  - Increase in the Prevalence of Atrophic Gastritis Among Adults Age 35 to 44 Years
      Old in Northern Sweden Between 1990 and 2009.
AB  - BACKGROUND & AIMS: Atrophic corpus gastritis (ACG) is believed to be an early
      precursor of gastric adenocarcinoma. We aimed to investigate trends of ACG in
      Northern Sweden, from 1990 through 2009, and to identify possible risk factors.
      METHODS: We randomly selected serum samples collected from 5284 participants in
      1990, 1994, 1999, 2004, and 2009, as part of the population-based, cross
      sectional Northern Sweden Multinational Monitoring of Trends and Determinants in
      Cardiovascular Disease study (ages, 35-64 y). Information was collected on
      sociodemographic, anthropometric, lifestyle, and medical factors using
      questionnaires. Serum samples were analyzed for levels of pepsinogen I to
      identify participants with functional ACG; data from participants with ACG were
      compared with those from frequency-matched individuals without ACG (controls).
      Blood samples were analyzed for antibodies against Helicobacter pylori and Cag
      pathogenicity island protein A. Associations were estimated with unconditional
      logistic regression models. RESULTS: Overall, 305 subjects tested positive for
      functional ACG, based on their level of pepsinogen I. The prevalence of ACG in
      participants age 55 to 64 years old decreased from 124 per 1000 to 49 per 1000
      individuals between 1990 and 2009. However, the prevalence of ACG increased from
      22 per 1000 to 64 per 1000 individuals among participants age 35 to 44 years old
      during this time period. Cag pathogenicity island protein A seropositivity was
      associated with risk for ACG (odds ratio, 2.29; 95% confidence interval, 1.69
      3.12). Other risk factors included diabetes, low level of education, and high
      body mass index. The association between body mass index and ACG was confined to
      individuals age 35 to 44 years old; in this group, overweight and obesity were
      associated with a 2.8-fold and a 4.7-fold increased risk of ACG, respectively.
      CONCLUSIONS: Among residents of Northern Sweden, the prevalence of ACG increased
      from 1990 through 2009, specifically among adults age 35 to 44 years old. The
      stabilizing seroprevalence of H pylori and the increasing prevalence of
      overweight and obesity might contribute to this unexpected trend. Studies are
      needed to determine whether these changes have affected the incidence of gastric
      cancer.

PMID- 25857684
TI  - Brain Activation During Emotional Memory Processing Associated with Subsequent
      Course of Depression.
AB  - Major depressive disorder (MDD) is characterized by a heterogeneous course and
      identifying patients at risk for an unfavorable course is difficult. Neuroimaging
      studies may identify brain predictors of clinical course and may help to further
      unravel the neurobiological processes underlying an unfavorable course. We
      investigated whether brain activation during an emotional memory paradigm is
      associated with depressive course. To this end, we followed 74 MDD patients and
      45 healthy controls (HCs) for 2 years. At baseline, participants performed an
      emotional word-encoding and -recognition task during functional magnetic
      resonance imaging. Activation patterns were compared between patients with fast
      remission (n=22), remission with recurrence (n=23), non-remission (n=29), and
      HCs. Additionally, linear relations of brain activation and time to remission
      during the follow-up period were investigated across patients. We observed that
      during encoding of negative words, non-remitters showed higher activation of the
      left insula than HCs. Groups also differed in activation of the right hippocampus
      and left amygdala during negative encoding, with a trend for higher activation in
      non-remitters compared with HCs. Furthermore, hippocampal activation during
      negative word encoding was significantly and positively correlated with time to
      remission, irrespective of illness severity. Our findings suggest that higher
      activation in the left insula could serve as a neural marker of a naturalistic
      non-remitting course, whereas higher hippocampal activation is associated with
      delayed remission. Longitudinal analyses should clarify whether abnormal
      activation progresses further as a function of time with depression or may serve
      as load-independent markers of MDD course. 

PMID- 25857686
TI  - Average thickness of tragal cartilage for slicing techniques in tympanoplasty.
AB  - BACKGROUND: Cartilage-perichondrial grafts are often used for tympanic membrane
      and middle-ear reconstructions. Tragal and conchal cartilages are most frequently
      used for this purpose. Studies have shown that slicing the cartilage to less than
      0.5 mm thickness improves acoustic benefit. However, the thickness of the
      cartilage in a given population may not be uniform. OBJECTIVE: This descriptive
      cross-sectional study aimed to determine the average thickness of tragal
      cartilage (in terms of age and sex) in an Indian population. METHOD: A
      prospective study of 61 tragal cartilages harvested during serial tympanoplasty
      and modified radical mastoidectomy were analysed according to thickness. RESULTS:
      The total average thickness of tragal cartilage was 1.228 +/- 0.204 mm in males
      and 1.090 +/- 0.162 mm in females. The overall thickness was 1.018 +/- 0.139 mm
      in those aged less than 15 years, 1.139 +/- 0.238 mm in those aged 15-30, and
      1.189 +/- 0.155 mm in those aged over 30 years. CONCLUSION: The findings help us
      to determine age-related cartilage thickness for slicing techniques in
      tympanoplasty.

PMID- 25857685
TI  - ApoE2 Exaggerates PTSD-Related Behavioral, Cognitive, and Neuroendocrine
      Alterations.
AB  - Apolipoprotein E (apoE) is an essential component of lipoprotein particles in
      both the brain and periphery, and exists in three isoforms in the human
      population: E2, E3, and E4. ApoE has numerous, well-established roles in
      neurobiology. Most notably, E4 is associated with earlier onset and increased
      risk of Alzheimer's disease (AD). Although possession of E2 is protective in the
      context of AD, E2 appears to confer an increased incidence and severity of
      posttraumatic stress disorder (PTSD). However, the biological processes
      underlying this link remain unclear. In this study, we began to elucidate these
      associations by examining the effects of apoE on PTSD severity in combat
      veterans, and on PTSD-like behavior in mice with human apoE. In a group of 92
      veterans with PTSD, we observed significantly higher Clinician-Administered PTSD
      Scale and PTSD Checklist scores in E2+ individuals, as well as alterations in
      salivary cortisol levels. Furthermore, we measured behavioral and biological
      outcomes in mice expressing human apoE after a single stressful event as well as
      following a period of chronic variable stress, a model of combat-related trauma.
      Mice with E2 showed impairments in fear extinction, and behavioral, cognitive,
      and neuroendocrine alterations following trauma. To the best of our knowledge,
      these data constitute the first translational demonstration of PTSD severity in
      men and PTSD-like symptoms in mice with E2, and point to apoE as a novel
      biomarker of susceptibility, and potential therapeutic target, for PTSD. 

PMID- 25857687
TI  - Gray matter atrophy is associated with functional connectivity reorganization
      during the Paced Auditory Serial Addition Test (PASAT) execution in Multiple
      Sclerosis (MS).
AB  - BACKGROUND AND PURPOSE: We explored the relationship between gray matter atrophy
      and reorganization of functional connectivity in multiple sclerosis patients
      during execution of the Paced Auditory Serial Addition Test (PASAT). MATERIALS
      AND METHODS: Seventeen patients and 15 healthy controls were selected for the
      study. Atrophy was determined using voxel-based morphometry, and atrophy-related
      connectivity changes were assessed using psychophysiological interaction
      analysis. Group differences, and correlations with PASAT performance and
      radiological variables were also examined. RESULTS: Gray matter atrophy in MS
      patients was circumscribed to the bilateral posterior cingulate gyrus/precuneus.
      Compared with controls, patients showed stronger connectivity between the left
      posterior cingulate gyrus/precuneus, and the left middle temporal gyrus and left
      cerebellum. A regression analysis in controls showed a negative correlation
      between PASAT scores and functional connectivity between: (1) the left posterior
      cingulate gyrus/precuneus, and left pre/postcentral gyri and left occipital
      gyrus, and (2) the right posterior cingulate gyrus/precuneus, and bilateral
      cerebellum and left pre/postcentral gyri. Patients showed a negative correlation
      between brain parenchymal fraction and functional connectivity between the left
      posterior cingulate gyrus/precuneus and left cerebellum. CONCLUSION: Patients
      with early MS and little brain damage presented more connectivity during PASAT
      execution, which may be interpreted as compensatory processes that help preserve
      cognitive functions.

PMID- 25857688
TI  - Excavating Meckel's cave: Cavum-trigeminale-cephaloceles (CTCs).
AB  - BACKGROUND AND PURPOSE: Cavum-trigeminale-cephaloceles (CTCs) are rare lesions of
      Meckel's cave and the petrous apex. Despite distinctive imaging features, they
      are frequently mistaken for other petrous apex lesions. In contrast to many of
      these entities, CTCs do--when asymptomatic--not require any invasive work-up or
      even surgical excision. Since correct diagnosis has profound impact on clinical
      decision-making, we report on a series of CTCs with distinct imaging features and
      their important differential diagnoses. MATERIAL AND METHODS: We report a
      retrospective series of 5 patients with CTCs and the associated imaging features
      including the absence of diffusion restriction and solid contrast enhancement as
      well as their size, anatomical location with regard to adjacent structures and
      the remodeling or erosion of surrounding bony structures. RESULTS: Our series
      contains the largest CTC that has, to the best of our knowledge, been reported so
      far. It revealed a deep cervical extension and was initially mistaken for a
      branchial cleft cyst. Furthermore, we show that CTCs can erode or remodel
      important structures such as canalis nervi hypoglossi, canalis Vidiani, foramen
      rotundum, ovale, lacerum and spinosum without causing clinical symptoms.
      CONCLUSION: In contrast to previous reports in which asymptomatic CTC did not
      include critical structures such as the foramina rotundum, ovale, lacerum or
      spinosum or the hypoglossal or Vidian canal, we show that CTCs can be
      asymptomatic even when eroding or remodeling such clinically important
      structures. When extending below the skull base, CTCs are a rare differential
      diagnosis to cystic cervical lesions such as type II branchial cleft cysts.

PMID- 25857689
TI  - Botulinum toxin in masticatory muscles of the adult rat induces bone loss at the
      condyle and alveolar regions of the mandible associated with a bone proliferation
      at a muscle enthesis.
AB  - In man, botulinum toxin type A (BTX) is injected in masticatory muscles for
      several indications such as trismus, bruxism, or masseter hypertrophy. Bone
      changes in the mandible following BTX injections in adult animal have therefore
      became a subject of interest. The aim of this study was to analyze condylar and
      alveolar bone changes following BTX unilateral injections in masseter and
      temporal muscles in adult rats. Mature male rats (n = 15) were randomized into 2
      groups: control (CTRL; n = 6) and BTX group (n= 9). Rats of the BTX group
      received a single injection of BTX into right masseter and temporal muscles. Rats
      of the CTRL group were similarly injected with saline solution. Rats were
      sacrificed 4 weeks after injections. Masticatory muscles examination and
      microcomputed tomography (microCT) were performed. A significant difference of
      weight was found between the 2 groups at weeks 2, 3 and 4 (p < 0.05). Atrophy of
      the right masseter and temporal muscles was observed in all BTX rats. MicroCT
      analysis showed significant bone loss in the right alveolar and condylar areas in
      BTX rats. Decrease in bone volume reached -20% for right alveolar bone and -35%
      for right condylar bone. A hypertrophic bone metaplasia at the digastric muscle
      enthesis was found on every right hemimandible in the BTX group and none in the
      CTRL group. BTX injection in masticatory muscles leads to a significant and major
      mandible bone loss. These alterations can represent a risk factor for fractures
      in human. The occurrence of a hypertrophic bone metaplasia at the Mus Digastricus
      enthesis may constitute an etiological factor for tori.

PMID- 25857690
TI  - Multi-level femoral morphology and mechanical properties of rats of different
      ages.
AB  - A macro-micro-nano-multi-level study was conducted to explore age-related
      structural and mechanical properties of bone, as well as the effects of aging on
      bone properties. A total of 70 male Wistar rats were used, ranging in the ages of
      1, 3, 5, 7, 9, 11, 14, 15, 16, and 17 months (n = 7/age group). After micro
      computed tomography (CT) scanning, longitudinal cortical bone specimens with a
      length of 5mm were cut along the femoral shaft axis from left femur shafts for
      mechanical testing, and the cross-sectional areas were measured. The macro
      mechanical properties obtained in mechanical testing and microarchitecture
      parameters measured by micro-CT were significantly correlated with the animal age
      (r(2) = 0.96, p < 0.001). Scanning electron microscopy was used for detecting the
      microarchitecture features of the fractured surfaces, which exhibited age-related
      plate-fibrous-mixed fibrous-plate texture, resulting in changes in macro
      mechanical properties (r(2) > 0.90, p < 0.001). The mineral phase of the left
      femoral shaft and head was analyzed by atomic force microscopy. Longitudinal and
      transverse trabecular bone tissues, as well as longitudinal cortical bone tissue,
      were used for nanoindentation test, and the chemical composition was evaluated by
      quantitative chemical analyses. The correlations between mineral content and bone
      material properties (i.e., elastic properties of the bone tissue and size and
      roughness of bone mineral grains) were highly significant (r > 0.95, p < 0.001).
      Multi-level femur morphology, mechanical property, and mineral content were
      significantly correlated with the animal age. The correlations between bone
      mineral content and bone material morphological and mechanical properties may
      partly explain the increase in bone fragility with aging, which will provide a
      theoretical basis for the investigation of age-related bone properties in
      clinics.

PMID- 25857691
TI  - [Clinical guideline for management of patients with low risk differentiated
      thyroid carcinoma].
AB  - Incidence of thyroid cancer is increasing in Spain and worldwide. Overall thyroid
      cancer survival is very high, and stratification systems to reliably identify
      patients with worse prognosis have been developed. However, marked differences
      exist between the different specialists in clinical management of low-risk
      patients with thyroid carcinoma. Almost half of all papillary thyroid carcinomas
      are microcarcinomas, and 90% are tumors < 2 cm that have a particularly good
      prognosis. However, they are usually treated more aggressively than needed,
      despite the lack of adequate scientific support. Surgery remains the gold
      standard treatment for these tumors. However, lobectomy may be adequate in most
      patients, without the need for total thyroidectomy. Similarly, prophylactic lymph
      node dissection of the central compartment is not required in most cases. This
      more conservative approach prevents postoperative complications such as
      hypoparathyroidism or recurrent laryngeal nerve injury. Postoperative radioiodine
      remnant ablation and strict suppression of serum thyrotropin, although effective
      for the more aggressive forms of thyroid cancer, have not been shown to be
      beneficial for the treatment of low risk patients, and may impair their quality
      of life. This guideline provides recommendations from the task force on thyroid
      cancer of the Spanish Society of Endocrinology and Nutrition for adequate
      management of patients with low-risk thyroid cancer.

PMID- 25857692
TI  - Kennedy's disease and partial androgen insensitivity syndrome. Report of 4 cases
      and literature review.
AB  - Kennedy's disease, also known as bulbospinal muscular atrophy, is a rare, X
      linked recessive neurodegenerative disorder affecting adult males. It is caused
      by expansion of an unstable cytosine-adenine-guanine tandem-repeat in exon 1 of
      the androgen-receptor gene on chromosome Xq11-12, and is characterized by spinal
      motor neuron progressive degeneration. Endocrinologically, these patients often
      have the features of hypogonadism associated to the androgen insensitivity
      syndrome, particularly its partial forms. We report 4 cases with the typical
      neurological presentation, consisting of slowly progressing generalized muscle
      weakness with atrophy and bulbar muscle involvement; these patients also had
      several endocrine manifestations; the most common non-neurological manifestation
      was gynecomastia. In all cases reported, molecular analysis showed an abnormal
      cytosine-adenine-guanine triplet repeat expansion in the androgen receptor gene.

PMID- 25857693
TI  - Statistical methods for association tests of multiple continuous traits in genome
      wide association studies.
AB  - Multiple correlated traits are often collected in genetic studies. The joint
      analysis of multiple traits could have increased power by aggregating multiple
      weak effects and offer additional insights into the aetiology of complex human
      diseases by revealing pleiotropic variants. We propose to study multivariate test
      statistics to detect single nucleotide polymorphism (SNP) association with
      multiple correlated traits. Most existing methods have been based on the
      generalized estimating equation (GEE) approach without explicitly modelling the
      trait correlations. In this article, we explore an alternative likelihood-based
      framework to test the multiple trait associations. It is based on the familiar
      multinomial logistic regression modelling of genotypes, which can be readily
      implemented using widely available software, and offers very competitive
      performance. We demonstrate through extensive numerical studies that the proposed
      method has competitive performance. Its usefulness is further illustrated with
      application to association analysis of diabetes-related traits in the
      Atherosclerosis Risk in Communities (ARIC) Study. 

PMID- 25857695
TI  - Illuminating biological processes through site-specific protein labeling.
AB  - Coupling genetically encoded peptide tags or unnatural amino acids (UAAs) with
      bioorthogonal reactions allows for precise control over the protein-labeling
      sites as well as the wide choice of labeling dyes. However, the value of these
      site-specific protein labeling strategies in a real biology setting, particularly
      their advantages over conventional labeling methods including fluorescent
      proteins (FPs), remains to be fully demonstrated. In this tutorial review, we
      first introduce various strategies for site-specific protein labeling that
      utilize artificial peptide sequences or genetically encoded UAAs as the labeling
      handle. Emphasis will be placed on introducing the advantages of protein site
      specific labeling techniques as well as their applications in solving biological
      problems, particularly as to why a site-specific protein labeling approach is
      needed. Finally, beyond the widely used single site-specific labeling methods,
      the recently emerged dual site-specific protein labeling strategies will be
      introduced together with their fast-growing potential in illustrating biological
      processes. 

PMID- 25857694
TI  - Mismatch between health-care professionals' and patients' views on a diabetes
      patient decision aid: a qualitative study.
AB  - BACKGROUND: Malaysia is an Asian country with population of diverse culture and
      health perceptions. Patient decision aid (PDA) is a new tool in Malaysia.
      Patients' and health-care professionals' (HCPs) expectation of a PDA is unknown.
      AIM: We aimed to explore patients' and health-care professionals'(HCPs) views on
      the information needed in a patient decision aid (PDA) on insulin initiation
      developed for patients with type 2 diabetes mellitus (T2DM). DESIGN: We used a
      qualitative design and thematic approach. SETTING: Three main primary health-care
      settings in Malaysia: public university-based primary care clinics, public health
      care clinics and private general practices. METHOD: We conducted focus groups and
      one-to-one interviews with a purposive sample of health professionals and
      patients with type 2 diabetes. RESULTS: We interviewed 18 patients and 13 HCPs.
      Patients viewed the content of the PDA as simple and clear. However, HCPs felt
      the PDA might be difficult for patients with low literacy to understand. HCPs
      thought the PDA was too lengthy. Nevertheless, patients would prefer more
      information. HCPs tended to focus on benefits of insulin, while patients wanted
      to know the impact of insulin on their quality of life and practical issues
      regarding insulin and its side-effects. Patients preferred numbers to weigh the
      risks and benefits of treatment options. HCPs' views that presenting numbers in a
      PDA would be too complex for patients to understand. CONCLUSION: It is important
      to consider including issues related to psycho-social impact of treatment to
      patients when developing a patient decision aid.

PMID- 25857696
TI  - Competing events and costs of clinical trials: Analysis of a randomized trial in
      prostate cancer.
AB  - BACKGROUND: Clinical trial costs may be reduced by identifying enriched
      subpopulations of patients with favorable risk profiles for the events of
      interest. However, increased selectivity affects accrual rates, with uncertain
      impact on clinical trial cost. METHODS: We conducted a secondary analysis of
      Southwest Oncology Group (SWOG) 8794 randomized trial of adjuvant radiotherapy
      for high-risk prostate cancer. The primary endpoint was metastasis-free survival
      (MFS), defined as time to metastasis or death from any cause (competing
      mortality). We used competing risks regression models to identify an enriched
      subgroup at high risk for metastasis and low risk for competing mortality. We
      applied a cost model to estimate the impact of enrichment on trial cost and
      duration. RESULTS: The treatment effect on metastasis was similar in the enriched
      subgroup (HR, 0.42; 95% CI, 0.23-0.76) compared to the whole cohort (HR, 0.50;
      95% CI, 0.30-0.81) while the effect on competing mortality was not significant in
      the subgroup or the whole cohort (HR 0.70; 95% CI 0.39-1.23, vs. HR 0.94; 95% CI,
      0.68-1.31). Due to the higher incidence of metastasis relative to competing
      mortality in the enriched subgroup, the treatment effect on MFS was greater in
      the subgroup compared to the whole cohort (HR 0.55; 95% CI 0.36-0.82, vs. HR
      0.77; 95% CI, 0.58-1.01). Trial cost was 75% less in the subgroup compared to the
      whole cohort ($1.7 million vs. $6.8 million), and the trial duration was 30%
      shorter (8.4 vs. 12.0 years). CONCLUSION: Competing event enrichment can reduce
      clinical trial cost and duration, without sacrificing generalizability.

PMID- 25857697
TI  - Identification and characterization of sORF-encoded polypeptides.
AB  - Molecular biology, genomics and proteomics methods have been utilized to reveal a
      non-annotated class of endogenous polypeptides (small proteins and peptides)
      encoded by short open reading frames (sORFs), or small open reading frames
      (smORFs). We refer to these polypeptides as s(m)ORF-encoded polypeptides or SEPs.
      The early SEPs were identified via genetic screens, and many of the RNAs that
      contain s(m)ORFs were originally considered to be non-coding; however, elegant
      work in bacteria and flies demonstrated that these s(m)ORFs code for functional
      polypeptides as small as 11-amino acids in length. The discovery of these initial
      SEPs led to search for these molecules using methods such as ribosome profiling
      and proteomics, which have revealed the existence of many SEPs, including novel
      human SEPs. Unlike screens, omics methods do not necessarily link a SEP to a
      cellular or biological function, but functional genomic and proteomic strategies
      have demonstrated that at least some of these newly discovered SEPs have
      biochemical and cellular functions. Here, we provide an overview of these results
      and discuss the future directions in this emerging field. 

PMID- 25857699
TI  - Antidepressant-like effects of magnesium lithospermate B in a rat model of
      chronic unpredictable stress.
AB  - CONTEXT: Magnesium lithospermate B (MLB), an active polyphenol acid of Danshen
      [Radix Salviae miltiorrhizae (Labiatae)], shows neuroprotective and anti
      inflammatory effects in vivo and in vitro. OBJECTIVE: We hypothesized that MLB
      might exert antidepressant-like effects by targeting the neuroinflammatory
      signals. MATERIALS AND METHODS: Sprague-Dawley rats were subjected to the chronic
      unpredictable stress (CUS) protocol. Rats in the control group received no CUS
      during the whole experiment. In the model group, rats were exposed to CUS for 7
      weeks. From the beginning of the 5th week, model group rats were randomly grouped
      and subjected to different treatments. In the experiment, control and model group
      rats were intraperitoneally (i.p.) injected with saline. MLB was dissolved in
      saline to give a final concentration, and the rats were injected (i.p.) with 15,
      30, or 60 mg/kg MLB once a day for 3 weeks. RESULTS: MLB administration
      significantly reduced: (1) the immobility time in the forced swimming test (19 s,
      p < 0.05); (2) the immobility time in the tail suspension test (76.3 s, p <
      0.05); (3) the corticosterone (CORT) concentrations in the serum (21.7 nmol/L, p
      > 0.05); (4) the pro-inflammatory cytokine levels in the serum - TNF-alpha (92.1
      pg/ml, p < 0.05), IL-1beta (86.9 pg/ml, p < 0.05), and IL-6 (93.8 pg/ml, p <
      0.05); (5) pro-inflammatory cytokine levels in tissue - TNF-alpha (3.2 pg/mg
      protein, p < 0.05), IL-1beta (1.5 pg/mg protein, p > 0.05), and IL-6 (6.3 pg/mg
      protein, p < 0.05); and (6) phospho-NF-kappaB (1.6, p < 0.05) and phospho-IkappaB
      alpha (0.4, p < 0.05) expression in tissue. DISCUSSION AND CONCLUSION: The
      results suggested that MLB might exert therapeutic actions on depression-like
      behavior and the HPA axis hyperactivity in CUS rats, and the mechanisms
      underlying the antidepressant-like effects of MLB might be mediated by regulation
      of the expression of NF-kappaB and IkappaB-alpha in rats.

PMID- 25857700
TI  - Four Moments for Patient Hand Hygiene: A Patient-Centered, Provider-Facilitated
      Model to Improve Patient Hand Hygiene.
AB  - We found that a majority of hospitalized patients were aware of the importance of
      hand hygiene, but observations indicated that performance of hand hygiene was
      uncommon. An intervention in which healthcare personnel facilitated hand hygiene
      at specific moments significantly increased performance of hand hygiene by
      patients.

PMID- 25857698
TI  - Postnatal ethanol exposure alters levels of 2-arachidonylglycerol-metabolizing
      enzymes and pharmacological inhibition of monoacylglycerol lipase does not cause
      neurodegeneration in neonatal mice.
AB  - The consumption of ethanol by pregnant women may cause neurological
      abnormalities, affecting learning and memory processes in children, and are
      collectively described as fetal alcohol spectrum disorders. However, the
      molecular mechanisms underlying these changes are still poorly understood. In our
      previous studies, we found that ethanol treatment of postnatal day 7 (P7) mice
      significantly enhances the anandamide levels but not the 2-arachidonylglycerol (2
      AG) levels and induces widespread neurodegeneration, but the reason for the lack
      of significant effects of ethanol on the 2-AG level is unknown. In this study, we
      examined developmental changes in diacylglycerol lipase-alpha, beta (DAGL-alpha
      and beta) and monoacylglycerol lipase (MAGL). We found that the levels of these
      proteins were significantly higher in adult brains compared to those detected
      early in brain development. Next, we examined the influence of P7 ethanol
      treatment on these enzymes, finding that it differentially altered the DAGL-alpha
      protein and mRNA levels but consistently enhanced those of the DAGL-beta.
      Interestingly, the ethanol treatment enhanced MAGL protein and mRNA levels.
      Inhibition of MAGL with KML29 failed to induce neurodegeneration in P7 mice.
      Collectively, these findings suggest that ethanol significantly activates DAGL
      beta and MAGL in the neonatal brain, resulting in no net change in 2-AG levels.

PMID- 25857701
TI  - Evaluating vaccination strategies for reducing infant respiratory syncytial virus
      infection in low-income settings.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of lower
      respiratory tract disease and related hospitalization of young children in least
      developed countries. Individuals are repeatedly infected, but it is the first
      exposure, often in early infancy, that results in the vast majority of severe RSV
      disease. Unfortunately, due to immunological immaturity, infants are a
      problematic RSV vaccine target. Several trials are ongoing to identify a suitable
      candidate vaccine and target group, but no immunization program is yet in place.
      METHODS: In this work, an individual-based model that explicitly accounts for the
      socio-demographic population structure is developed to investigate RSV
      transmission patterns in a rural setting of Kenya and to evaluate the potential
      effectiveness of alternative population targets in reducing RSV infant infection.
      RESULTS: We find that household transmission is responsible for 39% of infant
      infections and that school-age children are the main source of infection within
      the household, causing around 55% of cases. Moreover, assuming a vaccine-induced
      protection equivalent to that of natural infection, our results show that annual
      vaccination of students is the only alternative strategy to routine immunization
      of infants able to trigger a relevant and persistent reduction of infant
      infection (on average, of 35.6% versus 41.5% in 10 years of vaccination).
      Interestingly, if vaccination of pregnant women boosts maternal antibody
      protection in infants by an additional 4 months, RSV infant infection will be
      reduced by 31.5%. CONCLUSIONS: These preliminary evaluations support the efforts
      to develop vaccines and related strategies that go beyond targeting vaccines to
      those at highest risk of severe disease.

PMID- 25857703
TI  - Community-based educational intervention improved the diversity of complementary
      diets in western Kenya: results from a randomized controlled trial.
AB  - OBJECTIVE: Lack of diversity is a major factor contributing to inadequate
      nutrient intakes among children during the complementary feeding period in many
      rural areas in developing countries. This has been attributed to inadequate
      feeding practices and nutrition knowledge among their caregivers. The aim of the
      present study was to assess the effect of an educational intervention on
      children's dietary diversity and nutrition knowledge of caregivers. DESIGN:
      Cluster randomization was applied and twenty matched village pairs were randomly
      assigned to the intervention or control group. The nutrition education
      intervention consisted of four sessions comprising of group trainings and cooking
      demonstrations that were conducted over a period of 5 months. SETTING: Households
      in rural communities in Bondo and Teso South sub-counties, western Kenya.
      SUBJECTS: Caregivers with children aged 6-17 months receiving nutrition
      education. RESULTS: The children's dietary diversity scores (CDDS) and nutrition
      knowledge scores of the caregivers improved significantly in the intervention
      group at endline. The treatment effect on CDDS was positive and significant
      (P=0.001). The CDDS rate of the children in the intervention group was 27% larger
      than it would have been without the treatment effect. The intervention also had a
      significant effect on the caregivers' nutrition knowledge scores (incidence rate
      ratio=2.05; P<0.001). However, the nutrition knowledge of the caregivers did not
      have a significant effect on CDDS (P=0.731). CONCLUSIONS: The nutrition education
      intervention led to improvements in children's dietary diversity and nutrition
      knowledge of the caregivers.

PMID- 25857704
TI  - Stem cells and their potential therapeutic use in subacute sclerosing
      panencephalitis.

PMID- 25857705
TI  - Kartogenin, transforming growth factor-beta1 and bone morphogenetic protein-7
      coordinately enhance lubricin accumulation in bone-derived mesenchymal stem
      cells.
AB  - Osteoarthritis, a common joint degeneration, can cause breakdown of articular
      cartilage with the presence of lubricin metabolic abnormalities. Lubricin is a
      multi-level chondroprotective mucinous glycoprotein in articular joints. Joint
      defect and infection is elevated and accompanied by accelerated cartilage lesions
      involving degradation and loss of lubricin. However, a novel, heterocyclic
      compound called kartogenin (KGN) was discovered to stimulate chondrogenic
      differentiation of bone-derived mesenchymal stem cells (BMSCs). And the
      synergistic effect of transforming growth factor-beta1 (TGF-beta1) and bone
      morphogenetic protein-7 (BMP-7) could provoke lubricin accumulation. This paper
      attempted to explore the connection between accumulation of lubricin and the
      effect of TGF-beta1, BMP-7 and/or KGN. Hence, we investigated the expression and
      secretion of lubricin in BMSCs treated with different combinations of TGF-beta1,
      BMP-7, and/or KGN. Using an in vitro BMSCs system, we observed the content of
      lubricin from BMSCs treated with TGF-beta1, BMP-7, and KGN was the highest at
      both the protein level and the gene level. The accumulation of lubricin was
      enhanced coordinately by the increase of synthesis and decrease of degradation
      possibly via c-Myc and adamts5 pathway. These results further suggested that
      supplementation of the defect parts with lubricin by using growth factors and
      small molecules showed a promising potential on preventing joint deterioration in
      patients with acquired or genetic deficiency of lubricin in the future of
      regenerative medicine. 

PMID- 25857702
TI  - Diabetes mellitus related bone metabolism and periodontal disease.
AB  - Diabetes mellitus and periodontal disease are chronic diseases affecting a large
      number of populations worldwide. Changed bone metabolism is one of the important
      long-term complications associated with diabetes mellitus. Alveolar bone loss is
      one of the main outcomes of periodontitis, and diabetes is among the primary risk
      factors for periodontal disease. In this review, we summarise the adverse effects
      of diabetes on the periodontium in periodontitis subjects, focusing on alveolar
      bone loss. Bone remodelling begins with osteoclasts resorbing bone, followed by
      new bone formation by osteoblasts in the resorption lacunae. Therefore, we
      discuss the potential mechanism of diabetes-enhanced bone loss in relation to
      osteoblasts and osteoclasts. 

PMID- 25857706
TI  - TAOK3 phosphorylates the methylenecyclopropane nucleoside MBX 2168 to its
      monophosphate.
AB  - Monohydroxymethyl methylenecyclopropane nucleosides (MCPNs) with ether or
      thioether substituents at the 6-position show promise as broad-spectrum herpes
      virus inhibitors. Their proposed mechanism of action involves sequential
      phosphorylation to a triphosphate, which can then inhibit viral DNA polymerase.
      The inhibition of herpes simplex virus (HSV) by these compounds is not dependent
      on the viral thymidine kinase (TK), which is known to phosphorylate acyclovir
      (ACV), a standard treatment for HSV infections. Previous studies on the mechanism
      of action of these compounds against human cytomegalovirus (HCMV) implicated a
      host kinase in addition to HCMV UL97 kinase in performing the initial
      phosphorylation. After first eliminating other candidate HSV-1 encoded kinases
      (UL13 and US3) as well as potential host nucleoside kinases, using activity-based
      fractionation, we have now identified the host serine-threonine protein kinase
      TAOK3 as the kinase responsible for transforming the representative
      monohydroxymethyl MCPN analog MBX 2168 to its monophosphate. 

PMID- 25857707
TI  - Thiolated alkyl-modified carbomers: Novel excipients for mucoadhesive emulsions.
AB  - The aim of this study was the design and evaluation of mucoadhesive emulsifying
      polymeric excipients. Three thiol bearing ligands with increasing pKa values of
      their sulfhydryl group, namely 4-aminothiophenol (pKa=6.86), l-cysteine (pKa=8.4)
      and d/l-homocysteine (pKa=10.0) were coupled to the polymeric backbone of alkyl
      modified carbomer (PA1030). Resulting conjugates displayed 818.5MUmol 4
      aminothiophenol, 698.5MUmol cysteine and 651.5MUmol homocysteine per gram polymer
      and were evaluated regarding the reactivity of thiol groups, emulsifying and
      mucoadhesive properties. In general, the synthesized conjugates showed a pH
      dependent reactivity, whereby the fastest oxidation occurred in PA1030-cysteine,
      as almost no free thiol groups could be detected after 120min. Emulsification of
      medium chain triglycerides was feasible with all synthesized conjugates leading
      to oil-in-water-emulsions. Emulsions with PA1030-cysteine displayed the highest
      stability and the smallest droplet size among the tested formulations. Oxidation
      and consequently cross-linking of the thiomers prior to the emulsification
      process led to an overall decreased emulsion stability. Evaluating mucosal
      residence time of thiomer emulsions on porcine buccal mucosa, a 9.2-fold higher
      amount of formulation based on PA1030-cysteine remained on the mucosal tissue
      within 3h compared to the unmodified polymer. According to these results, the
      highest reactive ligand l-cysteine seems to be most promising in order to obtain
      thiolated polymers for the preparation of mucoadhesive o/w-emulsions. 

PMID- 25857708
TI  - 2'[(18)F]-fluoroethylrhodamine B is a promising radiotracer to measure P
      glycoprotein function.
AB  - In vivo detection of the emergence of P-glycoprotein (Pgp) mediated multidrug
      resistance in tumors could be beneficial for patients treated with anticancer
      drugs. PET technique in combination with appropriate radiotracers could be the
      most convenient method for detection of Pgp function. Rhodamine derivatives are
      validated fluorescent probes for measurement of mitochondrial membrane potential
      and also Pgp function. The aim of this study was to investigate whether 2'[(18)F]
      fluoroethylrhodamine B ((18)FRB) a halogenated rhodamine derivative previously
      synthesized for PET assessment of myocardial perfusion preserved its Pgp
      substrate character. ATPase assay as well as accumulation experiments carried out
      using Pgp(+) and Pgp(-) human gynecologic (A2780/A2780(AD) and KB-3-1/KB-V1) and
      a mouse fibroblast cell pairs (NIH 3T3 and NIH 3T3 MDR1) were applied to study
      the interaction of (18)FRB with Pgp. ATPase assay proved that (18)FRB is a high
      affinity substrate of Pgp. Pgp(-) cells accumulated the (18)FRB rapidly in
      accordance with its lipophilic character. Dissipation of the mitochondrial proton
      gradient by a proton ionophore CCCP decreased the accumulation of rhodamine 123
      (R123) and (18)FRB into Pgp(-) cells. Pgp(+) cells exhibited very low R123 and
      (18)FRB accumulation (around 1-8% of the Pgp(-) cell lines) which was not
      sensitive to the mitochondrial proton gradient; rather it was increased by the
      Pgp inhibitor cyclosporine A (CsA). Based on the above data we conclude that
      (18)FRB is a high affinity Pgp substrate and consequently a potential PET tracer
      to detect multidrug resistant tumors as well as the function of physiological
      barriers expressing Pgp. 

PMID- 25857709
TI  - Technical options for outflow reconstruction in domino liver transplantation: A
      single European center experience.
AB  - Venous outflow is critical to the success of liver transplantation (LT). In
      domino liver transplantation (DLT), the venous cuffs should be shared between the
      donor and the recipient, and the length can be compromised. The aim of this study
      was to describe and compare the technical options for outflow reconstruction used
      at our institution. This was a retrospective analysis of 39 consecutive DLT
      recipients between January 1997 and May 2013. Twenty-seven men and 12 women (mean
      age, 61.8 +/- 4.3 years) underwent LT and consented to receive a liver from a
      donor with familial amyloid polyneuropathy (FAP). The main indications were
      hepatocellular carcinoma and hepatitis C virus cirrhosis. All recipients
      underwent transplantation by a piggyback technique. Liver procurement in the FAP
      donors was performed with the classic technique in 22 patients and with the
      piggyback technique in the last 17. In these latter cases, for vascular outflow
      reconstruction, a cadaveric venous graft was interposed between the hepatic vein
      (HV) stump of the FAP liver and the recipient HV in 11 cases (28%). Since 2011,
      we have employed arterial grafts to be interposed between the vessels stumps: a
      tailored arterial graft in 5 patients and an aortic graft in 1 case. There was no
      postoperative mortality. Arterial and portal complications presented in 2 (5.1)
      and 4 patients (10.3), respectively. Postoperative outflow complications (post-LT
      subacute Budd-Chiari syndrome) occurred in 4 patients, and all of them had
      received a venous interposed graft for reconstruction. The incidence of outflow
      complications tended to be higher among patients with venous grafts than those
      with arterial graft interposition. Overall patient survival at 1, 3, 5, and 10
      years was 97%, 79%, respectively. Arterial grafts constitute a feasible and safe
      option for vascular outflow reconstruction in DLT because they are associated
      with a relatively low incidence of complications. The recently proposed Bellvitge
      arterial graft technique should be added to the current range of available
      surgical modalities.

PMID- 25857710
TI  - Improving practice at the point of care through the optimization of the
      breastfeeding resource nurse model.
AB  - OBJECTIVE: To describe and understand the Breastfeeding Resource Nurse (BRN) role
      and program. DESIGN: The primary study was a multimethod prospective study in
      which quantitative surveys and qualitative interviews of nurses who received
      education through the BRN program were used. Results presented herein are from
      the quantitative arm of the primary study. SETTING: A large free-standing urban
      children's hospital with a birthing unit for specialized deliveries and a primary
      and specialty care network. PARTICIPANTS: A total of 425 of 600 nurses who took
      the BRN course responded to the survey. These nurses worked in all settings
      throughout the enterprise. METHODS: The research team created a Survey Monkey
      interview that was e-mailed to all current nurses with valid hospital e-mail
      addresses who had taken the BRN course. Monthly e-mail reminders were sent and
      nurse managers were asked to encourage their staff to fill out the survey.
      RESULTS: Nurses who received specialized education through BRN course integrated
      the provision of evidence-based breastfeeding support and care into their daily
      routines. Furthermore, nurses became breastfeeding advocates and supported
      family, friends, and members of their communities in their breastfeeding
      experiences. CONCLUSIONS: The type of education needed for nurses who work at
      children's hospitals and in neonatal intensive care units is different than
      traditional breastfeeding education for birth hospitals. Implementation of the
      BRN course resulted in positive outcomes for staff; the course is transferrable
      to other facilities worldwide.

PMID- 25857712
TI  - Bureaucracy and budget revision: how spending cuts are affecting India's public
      health programmes.

PMID- 25857711
TI  - Sensitive measurement of total protein phosphorylation level in complex protein
      samples.
AB  - Measurement of protein phosphorylation plays an essential role in delineating
      cell signaling pathways. Although the detection of a specific phosphoprotein has
      been largely accomplished by immunological methods, a specific and sensitive
      assay to measure total protein phosphorylation level in complex samples such as
      whole cell extracts has yet to be established. Here, we present a sensitive
      phosphorylation assay on a microwell plate to determine total protein
      phosphorylation level calibrated to a phosphoprotein standard. The core of the
      assay is a reagent termed pIMAGO that is multi-functionalized with titanium ions
      for its superior selectivity towards phosphorylated proteins and with
      fluorophores for quantification. The specificity, sensitivity, and quantitative
      nature of the assay were demonstrated with standard proteins and whole cell
      lysates. The method was then employed to measure the overall protein
      phosphorylation level of human cells under different treatments. At last, we
      investigated the practicability of the assay to serve as a sensitive tool to
      estimate the amount of phosphorylated samples prior to a mass spectrometry-based
      phosphoproteomic analysis. 

PMID- 25857713
TI  - Basilar artery occlusion: Prognostic signs of severity on computed tomography.
AB  - PURPOSE: To determine the computed tomography (CT) signs that are predictive of
      the clinical outcome of basilar artery occlusion (BAO). MATERIALS AND METHODS:
      The study population consisted in 37 patients (14 women, 23 men, mean age: 63
      years), admitted with onset of neurological deficit, starting 1-72 h prior to
      admission, who were diagnosed with BAO on the basis of a CT examination with
      intravenous contrast agent. The following signs were collected on CT scans
      performed on admission: clot density on noncontrast images, clot length, and clot
      location, as well as the presence of acute ischemic lesions. The results were
      compared against the modified Rankin Scale (mRS) score of patients at 3 months,
      favorable clinical outcome being defined as a mRS score <=3. RESULTS: The
      clinical outcome was favorable in 13 (35%) of the 37 patients and unfavorable in
      24 (65%). Signs of acute ischemia were visible in 13 of the 24 patients with
      unfavorable outcome but in none of the 13 patients with favorable outcome
      (p<0.001). None of the other CT signs analyzed were significantly correlated with
      clinical prognosis. CONCLUSION: Of all the CT signs analyzed, only the presence
      of signs of acute ischemia on the admission CT of patients with BAO was
      associated with poor prognosis.

PMID- 25857714
TI  - Pharmacokinetics of hepatitis C virus NS5A inhibitor JNJ-56914845 (GSK2336805) in
      subjects with hepatic impairment.
AB  - JNJ-56914845 (GSK2336805) is a hepatitis C virus nonstructural protein 5A
      inhibitor under development for the treatment of chronic hepatitis C (CHC)
      infection. This open-label, parallel-group, 2-part study evaluated the
      pharmacokinetics and safety of a single oral 60 mg dose of JNJ-56914845 in 4
      cohorts: healthy, mild, moderate, and severe hepatic impairment (n = 8/cohort).
      Severity of hepatic impairment was categorized using Child-Pugh score, and the
      healthy subjects were matched for age, sex, body mass index, and smoking status
      to the moderate hepatic impairment cohort. JNJ-56914845 plasma AUC0-infinity was
      26%, 52%, and 45% lower in subjects with mild, moderate, and severe hepatic
      impairment, respectively, relative to healthy subjects with no difference in half
      life among the groups. The apparent oral clearance and volume of distribution
      were higher in subjects with hepatic impairment. The lower plasma concentrations
      were largely explained by decreased plasma protein binding in hepatically
      impaired subjects. One subject with severe hepatic impairment had 2 non-drug
      related serious adverse events: an esophageal bleed requiring hospitalization,
      encephalopathy. Although hepatically impaired subjects have lower exposures than
      healthy matched controls, they had similar or slightly higher exposures than
      those observed in past studies of noncirrhotic, CHC patients, suggesting that no
      dose adjustments for hepatic impairment will be needed. 

PMID- 25857715
TI  - 3D Pseudocontinuous arterial spin labeling in routine clinical practice: A review
      of clinically significant artifacts.
AB  - Arterial spin labeling (ASL) is a completely noninvasive magnetic resonance
      imaging (MRI) perfusion method for quantitatively measuring cerebral blood flow
      utilizing magnetically labeled arterial water. Advances in the technique have
      enabled the major MRI vendors to make the sequence available to the clinical
      neuroimaging community. Consequently, ASL is being increasingly incorporated into
      the routine neuroimaging protocol. Although a variety of ASL techniques are
      available, the ISMRM Perfusion Study Group and the European ASL in Dementia
      Consortium have released consensus guidelines recommending standardized
      implementation of 3D pseudocontinuous ASL with background suppression. The
      purpose of this review, aimed at the large number of neuroimaging clinicians who
      have either no or limited experience with this 3D pseudocontinuous ASL, is to
      discuss the common and clinically significant artifacts that may be encountered
      with this technique. While some of these artifacts hinder accurate interpretation
      of studies, either by degrading the images or mimicking pathology, there are
      other artifacts that are of clinical utility, because they increase the
      conspicuity of pathology. Cognizance of these artifacts will help the physician
      interpreting ASL to avoid potential diagnostic pitfalls, and increase their level
      of comfort with the technique.

PMID- 25857716
TI  - A selective molecularly imprinted polymer for immobilization of
      acetylcholinesterase (AChE): an active enzyme targeted and efficient method.
AB  - In the present study, we immobilized acetylcholinesterase (AChE) enzyme onto
      acetylcholine removed imprinted polymer and acetylcholine containing polymer.
      First, the polymers were produced with acetylcholine, substrate of AChE, by
      dispersion polymerization. Then, the enzyme was immobilized onto the polymers by
      using two different methods: In the first method (method A), acetylcholine was
      removed from the polymer, and then AChE was immobilized onto this polymer
      (acetylcholine removed imprinted polymer). In the second method (method B), AChE
      was immobilized onto acetylcholine containing polymer by affinity. In method A,
      enzyme-specific species (binding sites) occurred by removing acetylcholine from
      the polymer. The immobilized AChE reached 240% relative specific activity
      comparison with free AChE because the active enzyme molecules bounded onto the
      polymer. Transmission electron microscopy results were taken before and after
      immobilization of AChE for the assessment of morphological structure of polymer.
      Also, the experiments, which include optimum temperature (25-65  degrees C),
      optimum pH (3-10), thermal stability (4-70  degrees C), kinetic parameters,
      operational stability and reusability, were performed to determine the
      characteristic of the immobilized AChE.

PMID- 25857717
TI  - A novel modeling framework for ordinal data defined by collapsed counts.
AB  - Adolescent alcohol use is a serious public health concern. Despite advances in
      the theoretical conceptualization of pathways to alcohol use, researchers are
      limited by the statistical techniques currently available. Researchers often fit
      linear models and restrictive categorical models (e.g., proportional odds models)
      to ordinal data with many response categories defined by collapsed count data (0
      drinking days, 1-2 days, 3-6 days, etc.). Consequently, existing models ignore
      the underlying count process, resulting in disjoint between the construct of
      interest and the models being fitted. Our proposed ordinal modeling approach
      overcomes this limitation by explicitly linking ordinal responses to a suitable
      underlying count distribution. In doing so, researchers can use maximum
      likelihood estimation to fit count models to ordinal data as if they had directly
      observed the underlying discrete counts. The usefulness of our ordinal negative
      binomial and ordinal zero-inflated negative binomial models is verified by
      simulation studies. We also demonstrate our approach using real empirical data
      from the 2010 National Survey of Drug Use and Health. Results show the benefit of
      the proposed ordinal modeling framework compared with existing methods.

PMID- 25857718
TI  - Proteomic analysis of exosomes from nasopharyngeal carcinoma cell identifies
      intercellular transfer of angiogenic proteins.
AB  - Exosomes, a group of secreted extracellular nanovesicles containing genetic
      materials and signaling molecules, play a critical role in intercellular
      communication. During tumorigenesis, exosomes have been demonstrated to promote
      tumor angiogenesis and metastasis while their biological functions in
      nasopharyngeal carcinoma (NPC) are poorly understood. In this study, we focused
      on the role of NPC-derived exosomes on angiogenesis. Exosomes derived from the
      NPC C666-1 cells and immortalized nasopharyngeal epithelial cells (NP69 and
      NP460) were isolated using ultracentrifugation. The molecular profile and
      biophysical characteristics of exosomes were verified by Western blotting,
      sucrose density gradient and electron microscopy. We showed that the C666-1
      exosomes (10 and 20 MUg/ml) could significantly increase the tubulogenesis,
      migration and invasion of human umbilical vein endothelial cells (HUVECs) in a
      dose-dependent manner. Subsequently, an iTRAQ-based quantitative proteomics was
      used to identify the differentially expressed proteins in C666-1 exosomes. Among
      the 640 identified proteins, 51 and 89 proteins were considered as up- and down
      regulated (>= 1.5-fold variations) in C666-1 exosomes compared to the normal
      counterparts, respectively. As expected, pro-angiogenic proteins including
      intercellular adhesion molecule-1 (ICAM-1) and CD44 variant isoform 5 (CD44v5)
      are among the up-regulated proteins, whereas angio-suppressive protein,
      thrombospondin-1 (TSP-1) was down-regulated in C666-1 exosomes. Further confocal
      microscopic study and Western blotting clearly demonstrated that the alteration
      of ICAM-1 and TSP-1 expressions in recipient HUVECs are due to internalization of
      exosomes. Taken together, these data strongly indicated the critical roles of
      identified angiogenic proteins in the involvement of exosomes-induced
      angiogenesis, which could potentially be developed as therapeutic targets in
      future. 

PMID- 25857719
TI  - Analgesia and Improved Performance in a Patient Treated by Cooled Radiofrequency
      for Pain and Dysfunction Postbilateral Total Knee Replacement.
AB  - Total knee replacement (TKR) is a terminal therapy for osteoarthritis (OA) of the
      knee. While TKR results are generally satisfactory, a significant proportion of
      patients experience persistent pain lasting > 3 months following surgery, even
      after a technically acceptable operation. Knee pain of any kind post-TKR has been
      reported in up to 53% of patients, while 15% of patients have reported severe
      pain. Pain post-TKR is worse than preoperative pain in 7%, often resulting in
      surgical revision. The clinical experience of a patient that originally presented
      to an orthopedic surgeon with OA of both knees demonstrates an alternative
      relatively noninvasive pain management strategy: cooled radiofrequency (CRF)
      ablation of sensory nerves.

PMID- 25857721
TI  - Significance of chorionicity on long-term outcome of low birthweight infants of
      <1500g in twin pregnancies.
AB  - AIM: The aim of this study was to evaluate the long-term outcomes of very low
      birthweight twins by chorionicity and to identify the perinatal predictors for
      outcomes in the era of laser surgery for twin-twin transfusion syndrome. MATERIAL
      AND METHODS: This was a retrospective single-center cohort study of twin
      pregnancy infants <1500 g from 2003 through 2010. During the study period, laser
      surgery was performed on cases of twin-twin transfusion syndrome. The composite
      of adverse outcomes at 3 years of age was defined, including death, cerebral
      palsy, and developmental delay. The association between perinatal factors and
      adverse outcomes was evaluated by multiple logistic regression analysis. RESULTS:
      A total of 162 infants (79 dichorionic diamniotic twins [DCDA] and 83
      monochorionic diamniotic twins [MCDA]) were included in this study. Laser surgery
      was performed on 11 cases. The rate of adverse outcomes was 13.9% for DCDA and
      26.5% for MCDA. The incidence of each outcome for DCDA and MCDA was: cerebral
      palsy, 1.3% and 4.8%; developmental delay, 8.9% and 9.6%; and death, 3.8% and
      14.5%. Gestational age at birth (adjusted odds ratio: 0.69; 95% confidence
      interval, 0.57-0.84); and anemia at birth (adjusted odds ratio, 10.64; 95%
      confidence interval, 1.69-66.9) were independent risk factors, whereas
      chorionicity did not have significance for outcomes. CONCLUSION: The long-term
      outcome of very low birthweight MCDA was almost identical to that of DCDA.
      Gestational age and anemia at birth were independent risk factors for adverse
      outcomes.

PMID- 25857722
TI  - Within-day variation and influence of physical exercise on circulating Galectin-3
      in patients with rheumatoid arthritis and healthy individuals.
AB  - Galectin-3 has been suggested as a pro-inflammatory mediator in rheumatoid
      arthritis (RA). Previous studies have reported overexpression of Galectin-3 in RA
      synovitis and increased levels in synovial fluid and serum in long-standing RA
      compared with osteoarthritis and healthy controls. Our objectives were to study
      whether serum Galectin-3 (1) exhibits circadian variation and/or (2) responds to
      exercise in RA and controls. The study on circadian patterns (1) comprised eleven
      patients with newly diagnosed RA, disease duration less than 6 months (ERA), 10
      patients with long-standing RA [5-15 years (LRA)] and 16 self-reportedly healthy
      control subjects. During 24 h, 7 blood samples were drawn at 3-h intervals
      starting at 10 a.m. through 10 p.m. and at 7 and 10 a.m. on the following day.
      The study on the effect of physical activity (2) included 10 patients with ERA,
      10 with LRA and 14 controls. The participants underwent a standardized exercise
      programme and four blood samples were drawn before, during and after exercise.
      Serum Galectin-3 was quantified by ELISA (R&D systems). (1) Galectin-3 was
      increased at baseline in both RA subsets (P = 0.08). There were no diurnal
      oscillations (P = 0.85). Day-to-day variation amounted to 3%. (2) Baseline
      Galectin-3 was increased in LRA versus controls and ERA (P < 0.01 and 0.05).
      Physical exercise induced 10-15% Galectin-3 increments in RA and controls (P <
      0.001) peaking after 1-3 h. To conclude, Galectin-3 did not exhibit circadian
      variation. Day-to-day variation was 3%. Exercise elicited comparable increments
      in patients with RA of short and long duration and controls, approaching normal
      after 1-3 h.

PMID- 25857723
TI  - Structural and Biomechanical Properties of the Exchange Tissue of the Avian Lung.
AB  - The blood capillaries (BC) and the air capillaries (ACs) are the terminal gas
      exchange units of the avian lung. The minuscule structures are astonishingly
      strong. It is only recently that the morphologies and the biomechanical
      properties of the BCs and the ACs were investigated. Regarding size and shape,
      the BCs and the ACs differ remarkably. While they were previously claimed to be
      tubular (cylindrical) in shape, the ACs are rather rotund structures which
      interconnect across short, narrow passageways. Atypical of those in other
      tissues, the BCs in the exchange tissue of the avian lung comprise of distinct
      segments which are about as long as they are wide and which are coupled in three
      dimensions. The thin blood-gas barrier (BGB) which separates the ACs from the BCs
      is peculiarly strong. The causes of the strengths of the ACs and the BCs in
      general and the BGB in particular are varied and controversial. Here, the recent
      morphological and physiological findings on the structure, biomechanical
      properties, and the strengths of the respiratory units of the avian lung and the
      BGB have been critically examined. Also, in light of the new morphological
      findings of the ACs and the BCs, the functional model which is currently in use
      to assess the gas exchange efficiency of the avian lung should be revised and the
      inappropriateness of the terms 'blood capillary' and 'air capillary' for the gas
      exchange units of the avian lung is pointed out.

PMID- 25857724
TI  - Short-form RON overexpression augments benzyl isothiocyanate-induced apoptosis in
      human breast cancer cells.
AB  - Chemoprevention of breast cancer is feasible with the use of non-toxic
      phytochemicals from edible and medicinal plants. Benzyl isothiocyanate (BITC) is
      one such plant compound that prevents mammary cancer development in a transgenic
      mouse model in association with tumor cell apoptosis. Prior studies from our
      laboratory have demonstrated a role for reactive oxygen species (ROS)-dependent
      Bax activation through the intermediary of c-Jun N-terminal kinases in BITC
      induced apoptosis in human breast cancer cells. The present study demonstrates
      that truncated Recepteur d'Origine Nantais (sfRON) is a novel regulator of BITC
      induced apoptosis in breast cancer cells. Overexpression of sfRON in MCF-7 and
      MDA-MB-361 cells resulted in augmentation of BITC-induced apoptosis when the
      apoptotic fraction was normalized against vehicle control for each cell type
      (untransfected and sfRON overexpressing cells). ROS generation and G2 /M phase
      cell cycle arrest resulting from BITC treatment were significantly attenuated in
      sfRON overexpressing cells after normalization with vehicle control for each cell
      type. Increased BITC-induced apoptosis by sfRON overexpression was independent of
      c-Jun N-terminal kinase or p38 mitogen-activated protein kinase
      hyperphosphorylation. On the other hand, activation of Bax and Bak following BITC
      exposure was markedly more pronounced in sfRON overexpressing cells than in
      controls. sfRON overexpression also augmented apoptosis induction by structurally
      diverse cancer chemopreventive phytochemicals including withaferin A, phenethyl
      isothiocyanate, and D,L-sulforaphane. In conclusion, the present study provides
      novel mechanistic insights into the role of sfRON in apoptosis regulation by BITC
      and other electrophilic phytochemicals.

PMID- 25857725
TI  - The efficacy and safety of sirolimus-based graft-versus-host disease prophylaxis
      in patients undergoing allogeneic hematopoietic stem cell transplantation: a meta
      analysis of randomized controlled trials.
AB  - BACKGROUND: The efficacy and safety of sirolimus (SIR)-based graft-versus-host
      disease (GVHD) prophylaxis in patients who were subjected to allogeneic
      hematopoietic stem cell transplantation (allo-HSCT) remain to be clarified; this
      meta-analysis was conducted to evaluate these factors. STUDY DESIGN AND METHODS:
      Data from original research were obtained from PubMed, Embase, and Cochrane
      central register of controlled trials databases. Randomized controlled trials
      (RCTs) evaluating the efficacy of SIR-based prophylaxis in allo-HSCT were
      included. The risk ratio (RR), with a 95% confidence interval (CI), was used to
      pool data. The random effects model was used, irrespective of the presence or
      absence of heterogeneity. RESULTS: Five RCTs were included in the meta-analysis.
      SIR was observed to significantly decrease the incidence of Grade II to IV acute
      GVHD (aGVHD; RR, 0.65; 95% CI, 0.47-0.89). However, the incidence of Grade III to
      IV aGVHD and chronic GVHD was not decreased (RR, 0.91; 95% CI, 0.59-1.40; RR,
      1.04; 95% CI, 0.88-1.23, respectively). An analysis of the toxic effects of SIR
      revealed that SIR effected a significant increase in the incidence of sinusoidal
      obstructive syndrome (RR, 2.24; 95% CI, 1.26-4.01), while that of thrombotic
      microangiopathy was not significantly increased (RR, 2.48; 95% CI, 0.87-7.06).
      Moreover, SIR did not improve event-free survival and overall survival (RR, 0.97;
      95% CI, 0.85-1.10; and RR, 0.92; 95% CI, 0.82-1.02, respectively). CONCLUSION:
      This meta-analysis indicated that the SIR-based regimen is an effective and safe
      alternative prophylaxis strategy for GVHD.

PMID- 25857726
TI  - Disclosure of Sexual Intercourse by Teenagers: Agreement Between Telephone Survey
      Responses and Annual Visit Disclosures.
AB  - BACKGROUND: Physicians can help guide teenagers in their emerging sexuality;
      however, teens rarely inform physicians about their sexual activity. METHODS: We
      audio-recorded annual visits between 365 teenagers and 49 physicians. Before the
      recorded visit, the teens were asked in a confidential telephone survey whether
      they had ever engaged in sexual intercourse. Recordings were coded for teenage
      disclosures about previous sexual intercourse. We measured agreement between
      telephone survey responses and annual visit disclosures, and examined factors
      associated with agreement between the two. RESULTS: Fifty-six teenagers (15%)
      reported previous sexual intercourse in either the telephone survey or to their
      physician. Among those who reported sexual intercourse, 57% shared this
      information to both the telephone survey and their physician (kappa = .72,
      confidence interval = 0.63-0.82). CONCLUSIONS: Although a slight majority of
      teenagers disclosed their sexual activity to both the telephone survey and their
      doctor, a significant number disclosed to just one source.

PMID- 25857727
TI  - Peer Victimization in Extremely Low Birth Weight Survivors.
AB  - BACKGROUND: Extremely low birth weight (ELBW; <1000 g) children may be at risk
      for experiencing peer victimization. We examined retrospectively reported peer
      victimization in ELBW and control children in the oldest known, prospectively
      followed, population-based birth cohort of ELBW survivors. METHOD: We compared
      levels of verbal and physical peer victimization in ELBW and control children. We
      also predicted peer victimization in the ELBW sample from child characteristics.
      RESULTS: ELBW children, especially girls, were at an increased risk for verbal,
      but not physical victimization. In addition, ELBW children with a higher IQ
      reported higher levels of verbal victimization, although ELBW females who had a
      lower body mass index in childhood reported higher levels of physical
      victimization. CONCLUSION: Findings highlight the need for parents and clinicians
      to be aware that ELBW girls, especially those with a lower body mass index in
      childhood, may be at increased risk of peer victimization, as are ELBW children
      with a higher IQ.

PMID- 25857728
TI  - Risk Factors on Health-Related Quality of Life in Children With Epilepsy.
AB  - The goal of this study was to evaluate how epilepsy affected the health-related
      quality of life (HRQOL) in children with epilepsy, as well as the risk factors
      for poor HRQOL. Parents of epileptic children (n = 223) and parents of healthy
      children (n = 216) were enrolled. The Child Epilepsy Questionnaire-Parental form
      was given to all parents. Children with epilepsy had significantly lower HRQOL
      scores for overall QOL and all subscales. Seizure types were not associated with
      HRQOL, but the age of the child with epilepsy, disease courses and seizure
      frequency did influence the quality of life. Epilepsy has a severe impact on
      children's HRQOL, and age, increased seizure frequency and longer duration of
      epilepsy are associated with poor HRQOL. 

PMID- 25857729
TI  - Fever and Direct Hyperbilirubinemia.

PMID- 25857730
TI  - Knowledge of Child Development as a Predictor of Mother-Child Play Interactions.

PMID- 25857731
TI  - E-cadherin, beta-catenin, and alpha2beta1 and alpha3beta1 integrin expression in
      primary oral squamous cell carcinoma and its regional metastasis.
AB  - To investigate E-cadherin, beta-catenin, and alpha2beta1 and alpha3beta1
      integrins in 40 samples of non-metastatic and metastatic oral squamous cell
      carcinoma (OSCC) with positive cervical lymph nodes (LN). Immunohistochemistry
      was used to evaluate expression in the lesion center (LC) and invasive tumor
      front (ITF) of non-metastatic (n=18) and metastatic (n=22) OSCC and in the LN on
      the metastatic neoplastic cells (MNC; n=22). In metastatic OSCC, E-cadherin and
      beta-catenin presented significantly lower cytoplasmic membrane expression in the
      ITF and MNC when compared to the LC and lower cytoplasmic expression in MNC when
      compared to the LC and ITF (p<0.05). Integrins alpha2beta1 and alpha3beta1 showed
      high cytoplasmic expression in the LC, ITF and MNC (p>0.05). A positive
      correlation was observed between E-cadherin cytoplasmic expression and
      alpha2beta1 (p=0.860) and alpha3beta1 (p=0.975) expression. When comparing the
      primary sites of metastatic and non-metastatic disease, beta-catenin presented
      lower cytoplasmic membrane (p=0.013) expression in metastatic OSCC. E-cadherin
      presented low expression and the integrins high expression in both groups.
      Abnormal expression of beta-catenin and E-cadherin associated with high
      expression of alpha2beta1 and alpha3beta1 integrins contribute to LN metastasis
      in OSCC. 

PMID- 25857732
TI  - Seizure disorders in 43 cattle.
AB  - BACKGROUND: Large animals have a relatively high seizure threshold, and in most
      cases seizures are acquired. No published case series have described this
      syndrome in cattle. OBJECTIVES: To describe clinical findings and outcomes in
      cattle referred to the Veterinary Teaching Hospital of the University of Turin
      (Italy) because of seizures. ANIMALS: Client-owned cattle with documented
      evidence of seizures. METHODS: Medical records of cattle with episodes of
      seizures reported between January 2002 and February 2014 were reviewed. Evidence
      of seizures was identified based on the evaluation of seizure episodes by the
      referring veterinarian or 1 of the authors. Animals were recruited if physical
      and neurologic examinations were performed and if diagnostic laboratory test
      results were available. RESULTS: Forty-three of 49 cases fulfilled the inclusion
      criteria. The mean age was 8 months. Thirty-one animals were male and 12 were
      female. Piedmontese breed accounted for 39/43 (91%) animals. Seizures were
      etiologically classified as reactive in 30 patients (70%) and secondary or
      structural in 13 (30%). Thirty-six animals survived, 2 died naturally, and 5 were
      euthanized for reasons of animal welfare. The definitive cause of reactive
      seizures was diagnosed as hypomagnesemia (n = 2), hypocalcemia (n = 12), and
      hypomagnesemia-hypocalcemia (n = 16). The cause of structural seizures was
      diagnosed as cerebrocortical necrosis (n = 8), inflammatory diseases (n = 4), and
      lead (Pb) intoxication (n = 1). CONCLUSION AND CLINICAL IMPORTANCE: The study
      results indicate that seizures largely are reported in beef cattle and that the
      cause can be identified and successfully treated in most cases.

PMID- 25857733
TI  - Development and evaluation of murine lung-specific disease models for Pseudomonas
      aeruginosa applicable to therapeutic testing.
AB  - Pseudomonas aeruginosa is an opportunistic bacterial pathogen capable of causing
      a wide range of disease manifestations, including severe bacterial pneumonia.
      Recently, clinics have reported a rise in nosocomial infections with multidrug
      resistant (MDR) species, including MDR strains of P. aeruginosa. In order to
      quickly evaluate the efficacy of new therapeutics for MDR infections, highly
      reproducible and validated animal models need to be developed for pre-clinical
      testing. Here, we describe the characterization of two murine models to study MDR
      P. aeruginosa respiratory disease. We evaluated and compared these models using a
      non-invasive intratracheal instillation method and established the 50% lethal
      dose, course of infection, biometric parameters of disease and degree of
      pneumonia development for each model. Further, we tested meropenem as a proof-of
      concept therapeutic and report efficacy data that suggests that the leukopenic
      model could serve a robust pre-clinical model to test novel therapeutics. 

PMID- 25857735
TI  - Trafficking of Estrella lausannensis in human macrophages.
AB  - Estrella lausannensis is a new member of the Chlamydiales order. Like other
      Chlamydia-related bacteria, it is able to replicate in amoebae and in fish cell
      lines. A preliminary study investigating the pathogenic potential of Chlamydia
      related bacteria found a correlation between antibody response to E. lausannensis
      and pneumonia in children. To further investigate the pathogenic potential of E.
      lausannensis, we determined its ability to grow in human macrophages and its
      intracellular trafficking. The replication in macrophages resulted in viable E.
      lausannensis; however, it caused a significant cytopathic effect. The
      intracellular trafficking of E. lausannensis was analyzed by determining the
      interaction of the Estrella-containing inclusions with various endocytic markers
      as well as host organelles. The E. lausannensis inclusion escaped the endocytic
      pathway rapidly avoiding maturation into phagolysosomes by preventing both EEA-1
      and LAMP-1 accumulation. Compared to Waddlia chondrophila, another Chlamydia
      related bacteria, the recruitment of mitochondria and endoplasmic reticulum was
      minimal for E. lausannensis inclusions. Estrella lausannensis appears to use a
      distinct source of nutrients and energy compared to other members of the
      Chlamydiales order. In conclusion, we hypothesize that E. lausannensis has a
      restricted growth in human macrophages, due to its reduced capacity to control
      programmed cell death. 

PMID- 25857734
TI  - The genome sequence of four isolates from the family Lichtheimiaceae.
AB  - This study reports the release of draft genome sequences of two isolates of
      Lichtheimia corymbifera and two isolates of L. ramosa. Phylogenetic analyses
      indicate that the two L. corymbifera strains (CDC-B2541 and 008-049) are closely
      related to the previously sequenced L. corymbifera isolate (FSU 9682) while our
      two L. ramosa strains CDC-B5399 and CDC-B5792 cluster apart from them. These
      genome sequences will further the understanding of intraspecies and interspecies
      genetic variation within the Mucoraceae family of pathogenic fungi. 

PMID- 25857736
TI  - Vaccination with non-toxic mutant toxic shock syndrome toxin-1 induces IL-17
      dependent protection against Staphylococcus aureus infection.
AB  - Toxic shock syndrome toxin-1 (TSST-1) is one of superantigens produced by
      Staphylococcus aureus. We have previously demonstrated that vaccination with non
      toxic mutant TSST-1 (mTSST-1) develops host protection to lethal S. aureus
      infection in mice. However, the detailed mechanism underlying this protection is
      necessary to elucidate because the passive transfer of antibodies against TSST-1
      fails to provide complete protection against S. aureus infection. In this study,
      the results showed that interleukin-17A (IL-17A)-producing cells were increased
      in the spleen cells of mTSST-1-vaccinated mice. The main source of IL-17A in
      mTSST-1-vaccinated mice was T-helper 17 (Th17) cells. The protective effect of
      vaccination was induced when the vaccinated wild type but not IL-17A-deficient
      mice were challenged with S. aureus. Gene expression of chemokines, CCL2 and
      CXCL1, and infiltration of neutrophils and macrophages were increased in spleens
      and livers of vaccinated mice after infection. The IL-17A-dependent immune
      response was TSST-1 specific because TSST-1-deficient S. aureus failed to induce
      the response. The present study suggests that mTSST-1 vaccination is able to
      provide the IL-17A-dependent host defense against S. aureus infection which
      promotes chemokine-mediated infiltration of phagocytes into the infectious foci. 

PMID- 25857737
TI  - Gastrointestinal cancer screening: screening may release new research funding to
      improve health service also in routine clinics.
AB  - We are far from having seen the ideal method of screening for colorectal cancer
      (CRC) and the downsides of screening have not been fully addressed. Funding of
      adequately sized screening trials with a 10-15-year perspective for endpoints CRC
      mortality and incidence is difficult to get. Also, with such time horizons, there
      will always be an ongoing study to be awaited before feeling obliged to invest in
      the next. New, promising screening methods may, however, emerge far more often
      than every 10th year, and the knowledge gap may easily widen unless research is
      made a key responsibility for any ongoing cancer screening program. Previous lost
      battles on screening research may be won if accepting that scientific evidence
      may be obtained within the framework of screening programs - provided that they
      are designed as platforms for Comparative Effectiveness Research (CER). Accepting
      that CER-based screening programs should be preferred to non-CER programs and
      seriously compete for their funding sources, then CER screening programs may not
      be considered so much as contenders for ordinary clinical research funds. Also,
      CER within a screening framework may benefit patients in routine clinics as shown
      by screening research in Nordic countries. The Nordic countries have been early
      contributors to research on CRC screening, but slow in implementing screening
      programs. 

PMID- 25857738
TI  - Maternal diet as a modifier of offspring epigenetics.
AB  - There has been a substantial body of evidence, which has shown that genetic
      variation is an important determinant of disease risk. However, there is now
      increasing evidence that alterations in epigenetic processes also play a role in
      determining susceptibility to disease. Epigenetic processes, which include DNA
      methylation, histone modifications and non-coding RNAs play a central role in
      regulating gene expression, determining when and where a gene is expressed as
      well as the level of gene expression. The epigenome is highly sensitive to a
      variety of environmental factors, especially in early life. One factor that has
      been shown consistently to alter the epigenome is maternal diet. This review will
      focus on how maternal diet can modify the epigenome of the offspring, producing
      different phenotypes and altered disease susceptibilities. 

PMID- 25857739
TI  - Association of in vitro fertilization with global and IGF2/H19 methylation
      variation in newborn twins.
AB  - In vitro fertilization (IVF) and its subset intracytoplasmic sperm injection
      (ICSI), are widely used medical treatments for conception. There has been
      controversy over whether IVF is associated with adverse short- and long-term
      health outcomes of offspring. As with other prenatal factors, epigenetic change
      is thought to be a molecular mediator of any in utero programming effects. Most
      studies focused on DNA methylation at gene-specific and genomic level, with only
      a few on associations between DNA methylation and IVF. Using buccal epithelium
      from 208 twin pairs from the Peri/Postnatal Epigenetic Twin Study (PETS), we
      investigated associations between IVF and DNA methylation on a global level,
      using the proxies of Alu and LINE-1 interspersed repeats in addition to two locus
      specific regulatory regions within IGF2/H19, controlling for 13 potentially
      confounding factors. Using multiple correction testing, we found strong evidence
      that IVF-conceived twins have lower DNA methylation in Alu, and weak evidence of
      lower methylation in one of the two IGF2/H19 regulatory regions and LINE-1,
      compared with naturally conceived twins. Weak evidence of a relationship between
      ICSI and DNA methylation within IGF2/H19 regulatory region was found, suggesting
      that one or more of the processes associated with IVF/ICSI may contribute to
      these methylation differences. Lower within- and between-pair DNA methylation
      variation was also found in IVF-conceived twins for LINE-1, Alu and one IGF2/H19
      regulatory region. Although larger sample sizes are needed, our results provide
      additional insight to the possible influence of IVF and ICSI on DNA methylation.
      To our knowledge, this is the largest study to date investigating the association
      of IVF and DNA methylation. 

PMID- 25857740
TI  - Ectopic pancreatic tissue in the jejunal mesentery.

PMID- 25857741
TI  - Immunomodulator 'mushroom beta glucan' induces Wnt/beta catenin signalling and
      improves wound recovery in tilapia and rat skin: a histopathological study.
AB  - The present study aims to investigate the effects of mushroom beta glucan (MBG)
      on wound recovery in partial hepatectomy (PH) in Nile tilapia (Oreochromis
      niloticus) and in rat skin wound healing examination. Following PH, we focussed
      on the effects on liver repair ability using in vitro and in vivo tests. In
      vitro, we examined whether the MBG has an impact on liver cell proliferation,
      mainly through 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT)
      assays and bromodeoxyuridine (BrdU) cell proliferation assay detection method.
      Results showed that MBG treatment was remarkable in enhancing cell proliferation
      of hepatocytes and in maintaining the cellular viability. Immunohistochemical
      staining to analyse Wnt/beta-catenin signalling also showed that MBG has the
      effect of promoting cell proliferation of liver tissues after PH surgery.

PMID- 25857742
TI  - Enhanced electrical properties at boundaries including twin boundaries of
      polycrystalline CdTe thin-film solar cells.
AB  - The effect of grain boundaries (GBs), in particular twin boundaries (TBs), on
      CdTe polycrystalline thin films is studied by conductive atomic force microscopy
      (C-AFM), electron-beam-induced current (EBIC), scanning Kelvin probe microscopy
      (SKPM), electron backscatter diffraction (EBSD), and scanning transmission
      electron microscopy (STEM). Four types of CdTe grains with various densities of
      {111} Sigma3 twin boundaries (TBs) are found in Cl-treated CdTe polycrystalline
      thin films: (1) grains having multiple {111} Sigma3 TBs with a low angle to the
      film surface; (2) grains having multiple {111} Sigma3 TBs parallel to the film
      surfaces; (3) small grains on a scale of not more than 500 nm, composed of Cd,
      Cl, Te, and O; and (4) CdTe grains with not more than two {111} Sigma3 TBs. Grain
      boundaries (including TBs) exhibit enhanced current transport phenomena. However,
      the {111} Sigma3 TB is much more beneficial to micro-current transport. The
      enhanced current transport can be explained by the lower electron potential at
      GBs (including TBs) than the grain interiors (GIs). Our results open new
      opportunities for enhancing solar cell performances by controlling the grain
      boundaries, and in particular TBs. 

PMID- 25857743
TI  - [Pharmacokinetics, metabolism, and analytical methods of ethanol].
AB  - Alcohol is a licit substance whose significant consumption is responsible for a
      major public health problem. Every year, a large number of deaths are related to
      its consumption. It is also involved in various accidents, on the road, at work,
      as well as during acts of violence. Ethanol absorption and its fate are detailed.
      It is mainly absorbed in the small intestine. It accompanies the movements of the
      water, so it diffuses in all the tissues uniformly with the exception of bones
      and fat. The major route of ethanol detoxification is located into the liver.
      Detoxification is a saturable two-step oxidation. During the first stage ethanol
      is oxidized into acetaldehyde, under the action of alcohol dehydrogenase. During
      the second stage acetaldehyde is oxidized into acetate. Genetic factors or some
      drugs are able to disturb the absorption and the metabolism of ethanol. The
      analytical methods for the quantification of alcohol in man include analysis in
      exhaled air and in blood. The screening and quantification of ethanol for road
      safety are performed in exhaled air. In hospitals, blood ethanol determination is
      routinely performed by enzymatic method, but the rule for forensic samples is gas
      chromatography. 

PMID- 25857744
TI  - [The glycated hemoglobin: indication, interpretation and limitations].
AB  - HbA1c is defined by the slow and irreversible binding of glucose to the N
      terminal valine of one or both of the beta chains of hemoglobin A (HbA). It is a
      marker that is becoming increasingly important because of its role in both the
      diagnosis and monitoring of diabetic patients with type 1 and type 2. It reflects
      glycemic control of two or three months. Learned societies such as the IFCC and
      NGSP contributed to its standardization, which allows inter-laboratory comparison
      of results. Its assay uses chromatographic, electrophoretic or immunochemical
      methods. The HbA1c concentration is expressed in percent and in mmol/mol, and a
      number that is between 4 and 6% (20 and 42mmol/mol) is desirable. However, HbA1c
      cannot be used in some cases and fructosamine assay must be considered. 

PMID- 25857746
TI  - Geometry flexibility of copper iodide clusters: variability in luminescence
      thermochromism.
AB  - An original copper(I) iodide cluster of novel geometry obtained by using a
      diphosphine ligand is reported and is formulated [Cu6I6(PPh2(CH2)3PPh2)3] (1).
      Interestingly, this sort of "eared cubane" cluster based on the [Cu6I6] inorganic
      core can be viewed as a combination of the two known [Cu4I4] units, namely, the
      cubane and the open-chair isomeric geometries. The synthesis, structural and
      photophysical characterisations, as well as theoretical study of this copper
      iodide along with the derived cubane (3) and open-chair (2) [Cu4I4(PPh3)4] forms,
      were investigated. A new polymorph of the cubane [Cu4I4(PPh3)4] cluster is indeed
      presented (3). The structural differences of the clusters were analyzed by solid
      state nuclear magnetic resonance spectroscopy. Luminescence properties of the
      three clusters were studied in detail as a function of the temperature showing
      reversible luminescence thermochromism for 1 with an intense orange emission at
      room temperature. This behavior presents different feature compared to the cubane
      cluster and completely contrasts with the open isomer, which is almost
      nonemissive at room temperature. Indeed, the thermochromism of 1 differs by a
      concomitant increase of the two emission bands by lowering the temperature, in
      contrast to an equilibrium phenomenon for 3. The luminescence properties of 2 are
      very different by exhibiting only one single band when cooled. To rationalize the
      different optical properties observed, density functional theory calculations
      were performed for the three clusters giving straightforward explanation for the
      different luminescence thermochromism observed, which is attributed to different
      contributions of the ligands to the molecular orbitals. Comparison of 3 with its
      [Cu4I4(PPh3)4] cubane polymorphs highlights the sensibility of the emission
      properties to the cuprophilic interactions. 

PMID- 25857747
TI  - Tethering of nicotinamide adenine dinucleotide inside hollow nanofibers for high
      yield synthesis of methanol from carbon dioxide catalyzed by coencapsulated
      multienzymes.
AB  - Enzymatic conversion of carbon dioxide (CO2) to fuel or chemicals is appealing,
      but is limited by lack of efficient technology for regeneration and reuse of
      expensive cofactors. Here we show that cationic polyelectrolyte-doped hollow
      nanofibers, which can be fabricated via a facile coaxial electrospinning
      technology, provide an ideal scaffold for assembly of cofactor and multienzymes
      capable of synthesizing methanol from CO2 through a cascade multistep reaction
      involving cofactor regeneration. Cofactor and four enzymes including formate,
      formaldehyde, alcohol, and glutamate dehydrogenases were in situ coencapsulated
      inside the lumen of hollow nanofibers by involving them in the core-phase
      solution for coaxial electrospinning, in which cationic polyelectrolyte was
      predissolved. The polyelectrolyte penetrating across the shell of the hollow
      nanofibers enabled efficient tethering and retention of cofactor inside the lumen
      via ion-exchange interactions between oppositely charged polyelectrolytes and
      cofactor. With carbonic anhydrase assembled on the outer surface of the hollow
      nanofibers for accelerating hydration of CO2, these five-enzymes-cofactor
      catalyst system exhibited high activity for methanol synthesis. Compared with
      methanol yield of only 36.17% using free enzymes and cofactor, the hollow
      nanofiber-supported system afforded a high value up to 103.2%, the highest
      reported value so far. It was believed that the linear polyelectrolytes acted as
      spacers to enhance the shuttling of cofactor between enzymes that were
      coencapsulated within near vicinity, thus improving the efficiency of the system.
      The immobilized system showed good stability in reusing. About 80% of its
      original productivity was retained after 10 reusing cycles, with a cofactor-based
      cumulative methanol yield reached 940.5%. 

PMID- 25857745
TI  - Roles of lymphatic endothelial cells expressing peripheral tissue antigens in CD4
      T-cell tolerance induction.
AB  - Lymphatic endothelial cells (LECs) directly express peripheral tissue antigens
      and induce CD8 T-cell deletional tolerance. LECs express MHC-II molecules,
      suggesting they might also tolerize CD4 T cells. We demonstrate that when beta
      galactosidase (beta-gal) is expressed in LECs, beta-gal-specific CD8 T cells
      undergo deletion via the PD-1/PD-L1 and LAG-3/MHC-II pathways. In contrast, LECs
      do not present endogenous beta-gal in the context of MHC-II molecules to beta-gal
      specific CD4 T cells. Lack of presentation is independent of antigen
      localization, as membrane-bound haemagglutinin and I-Ealpha are also not
      presented by MHC-II molecules. LECs express invariant chain and cathepsin L, but
      not H2-M, suggesting that they cannot load endogenous antigenic peptides onto MHC
      II molecules. Importantly, LECs transfer beta-gal to dendritic cells, which
      subsequently present it to induce CD4 T-cell anergy. Therefore, LECs serve as an
      antigen reservoir for CD4 T-cell tolerance, and MHC-II molecules on LECs are used
      to induce CD8 T-cell tolerance via LAG-3. 

PMID- 25857748
TI  - Magnetic resonance angiography or digital subtraction catheter angiography for
      follow-up of coiled aneurysms: do we need both?
AB  - INTRODUCTION: Endovascular treatment of intracranial aneurysms is now common.
      Digital subtraction catheter angiography (DSA) is the gold standard for imaging
      follow-up of coiled intracranial aneurysms; however, it is an invasive procedure
      with a risk of complications. Time-of-flight magnetic resonance angiography (MRA)
      is an alternative non-invasive imaging method. In a previous study, we found that
      MRA at 1.5T was comparable to DSA for detection of aneurysm recurrence in this
      patient group and subsequently added MRA to the routine follow-up protocol. In
      the current study, we further compare MRA with DSA to determine whether MRA could
      safely replace DSA. METHODS: Patients who had endovascular coiling procedure for
      intracranial aneurysm from 10/2004 to 6/2010 were identified from our database. A
      radiologist and a radiology registrar compared MRA and DSA for all patients who
      received both modalities. DSA was considered as the reference technique.
      'Agreement' or 'disagreement' between modalities was noted regarding absence or
      presence of aneurysm recurrence. RESULTS: The study group comprised 86 treatments
      of 80 aneurysms in 73 patients. There were 83/86 agreements between modalities
      and 3 disagreements. In one case, MRA identified a recurrence that was not seen
      on the corresponding DSA. In two cases, DSA showed a minor recurrence that was
      not seen on MRA. CONCLUSION: Of the two MRA 'misses', neither would have resulted
      in different management. MRA is a safe and accurate modality for follow-up of
      coiled aneurysms and can replace DSA.

PMID- 25857752
TI  - User-friendly 3D bioassays with cell-containing hydrogel modules: narrowing the
      gap between microfluidic bioassays and clinical end-users' needs.
AB  - Cell-containing hydrogel modules as cell-hydrogel microunits for creating a
      physiologically relevant 3D in vivo-like microenvironment with multiple cell
      types and unique extracellular matrix (ECM) compositions facilitate long-term
      cell maintenance and bioassays. To date, there have been many important advances
      in microfluidic bioassays, which incorporate hydrogel scaffolds into surface
      accessible microchambers, driven by the strong demand for the application of
      spatiotemporally defined biochemical stimuli to construct in vivo-like conditions
      and perform real-time imaging of cell-matrix interactions. In keeping with the
      trend of fostering collaborations among biologists, clinicians, and microfluidic
      engineers, it is essential to create a simpler approach for coupling cell
      containing hydrogel modules and an automated bioassay platform in a user-friendly
      format. In this article, we review recent progress in hydrogel-incorporated
      microfluidics for long-term cell maintenance and discuss some of the simpler and
      user-friendly 3D bioassay techniques combined with cell-containing hydrogel
      modules that can be applied to mutually beneficial collaborations with non
      engineers. We anticipate that this modular and user-friendly format interfaced
      with existing laboratory infrastructure will help address several clinical
      questions in ways that extend well beyond the current 2D cell-culture systems. 

PMID- 25857750
TI  - Mitophagy and the mitochondrial unfolded protein response in neurodegeneration
      and bacterial infection.
AB  - Mitochondria are highly dynamic and structurally complex organelles that provide
      multiple essential metabolic functions. Mitochondrial dysfunction is associated
      with neurodegenerative conditions such as Parkinson's disease, as well as
      bacterial infection. Here, we explore the roles of mitochondrial autophagy
      (mitophagy) and the mitochondrial unfolded protein response (UPR(mt)) in the
      response to mitochondrial dysfunction, focusing in particular on recent evidence
      on the role of mitochondrial import efficiency in the regulation of these stress
      pathways and how they may interact to protect the mitochondrial pool while
      initiating an innate immune response to protect against bacterial pathogens.

PMID- 25857753
TI  - Ecologically and geologically relevant isotope signatures of C, N, and S: okenone
      producing purple sulfur bacteria Part I.
AB  - Purple sulfur bacteria (PSB) are known to couple the carbon, nitrogen, and sulfur
      cycling in euxinic environments. This is the first study with multiple strains
      and species of okenone-producing PSB to examine the carbon (C), nitrogen (N), and
      sulfur (S) metabolisms and isotopic signatures in controlled laboratory
      conditions, investigating what isotopic fractionations might be recorded in
      modern environments and the geologic record. PSB play an integral role in the
      ecology of euxinic environments and produce the unique molecular fossil okenane,
      derived from the diagenetic alteration of the carotenoid pigment okenone.
      Cultures of Marichromatium purpuratum 1591 (Mpurp1591) were observed to have
      carbon isotope fractionations ((13)epsilon biomass - CO2), via RuBisCO, ranging
      from -16.1 to -23.20/00 during exponential and stationary phases of growth.
      Cultures of Thiocapsa marina 5653 (Tmar5653) and Mpurp1591 had a nitrogen isotope
      fractionation ((15)epsilon biomass - NH 4) of -150/00, via glutamate
      dehydrogenase, measured and recorded for the first time in PSB. The delta(34)
      SVCDT values and amount of stored elemental sulfur for Mpurp1591 cells grown
      autotrophically and photoheterotrophically were dependent upon their carbon
      metabolic pathways. We show that PSB may contribute to the isotopic enrichments
      observed in modern and ancient anoxic basins. In a photoheterotrophic culture of
      Mpurp1591 that switched to autotrophy once the organic substrate was consumed,
      there were bulk biomass delta(13)C values that span a broader range than recorded
      across the Late Devonian, Permian-Triassic, Triassic-Jurassic, and OAE2 mass
      extinction boundaries. This finding stresses the complexities in interpreting and
      assigning delta(13)C values to bulk organic matter preserved in the geologic
      record.

PMID- 25857751
TI  - Plasma FGF21 concentrations, adipose fibroblast growth factor receptor-1 and beta
      klotho expression decrease with fasting in northern elephant seals.
AB  - Fibroblast growth factor (FGF)-21 is secreted from the liver, pancreas, and
      adipose in response to prolonged fasting/starvation to facilitate lipid and
      glucose metabolism. Northern elephant seals naturally fast for several months,
      maintaining a relatively elevated metabolic rate to satisfy their energetic
      requirements. Thus, to better understand the impact of prolonged food deprivation
      on FGF21-associated changes, we analyzed the expression of FGF21, FGF receptor-1
      (FGFR1), beta-klotho (KLB; a co-activator of FGFR) in adipose, and plasma FGF21,
      glucose and 3-hydroxybutyrate in fasted elephant seal pups. Expression of FGFR1
      and KLB mRNA decreased 98% and 43%, respectively, with fasting duration. While
      the 80% decrease in mean adipose FGF21 mRNA expression with fasting did not reach
      statistical significance, it paralleled the 39% decrease in plasma FGF21
      concentrations suggesting that FGF21 is suppressed with fasting in elephant
      seals. Data demonstrate an atypical response of FGF21 to prolonged fasting in a
      mammal suggesting that FGF21-mediated mechanisms have evolved differentially in
      elephant seals. Furthermore, the typical fasting-induced, FGF21-mediated actions
      such as the inhibition of lipolysis in adipose may not be required in elephant
      seals as part of a naturally adapted mechanism to support their unique metabolic
      demands during prolonged fasting. 

PMID- 25857754
TI  - Pigment production and isotopic fractionations in continuous culture: okenone
      producing purple sulfur bacteria Part II.
AB  - Okenone is a carotenoid pigment unique to certain members of Chromatiaceae, the
      dominant family of purple sulfur bacteria (PSB) found in euxinic photic zones.
      Diagenetic alteration of okenone produces okenane, the only recognized molecular
      fossil unique to PSB. The in vivo concentrations of okenone and
      bacteriochlorophyll a (Bchl a) on a per cell basis were monitored and quantified
      as a function of light intensity in continuous cultures of the purple sulfur
      bacterium Marichromatium purpuratum (Mpurp1591). We show that okenone-producing
      PSB have constant bacteriochlorophyll to carotenoid ratios in light-harvesting
      antenna complexes. The in vivo concentrations of Bchl a, 0.151 +/- 0.012 fmol
      cell(-1), and okenone, 0.103 +/- 0.012 fmol cell(-1), were not dependent on
      average light intensity (10-225 Lux) at both steady and non-steady states. This
      observation revealed that in autotrophic continuous cultures of Mpurp1591, there
      was a constant ratio for okenone to Bchl a of 1:1.5. Okenone was therefore
      constitutively produced in planktonic cultures of PSB, regardless of light
      intensity. This confirms the legitimacy of okenone as a signature for autotrophic
      planktonic PSB and by extrapolation water column euxinia. We measured the
      delta(13)C, delta(15)N, and delta(34)S bulk biomass values from cells collected
      daily and determined the isotopic fractionations of Mpurp1591. There was no
      statistical relationship in the bulk isotope measurements or stable isotope
      fractionations to light intensity or cell density under steady and non-steady
      state conditions. The carbon isotope fractionation between okenone and Bchl a
      with respect to overall bulk biomass ((13)epsilon pigment - biomass) was 2.2 +/-
      0.40/00 and -4.1 +/- 0.90/00, respectively. The carbon isotopic fractionation
      (13epsilon pigment-CO2) for the production of pigments in PSB is more variable
      than previously thought with our reported values for okenone at -15.5 +/- 1.20/00
      and -21.8 +/- 1.70/00 for Bchl a.

PMID- 25857755
TI  - Gender difference in N170 elicited under oddball task.
AB  - BACKGROUND: Some studies have reported gender differences in N170, a face
      selective event-related potential (ERP) component. This study investigated gender
      differences in N170 elicited under oddball paradigm in order to clarify the
      effect of task demand on gender differences in early facial processing. FINDINGS:
      Twelve males and 10 females discriminated targets (emotional faces) from non
      targets (emotionally neutral faces) under an oddball paradigm, pressing a button
      as quickly as possible in response to the target. Clear N170 was elicited in
      response to target and non-target stimuli in both males and females. However,
      females showed more negative amplitude of N170 in response to target compared
      with non-target, while males did not show different N170 responses between target
      and non-target. CONCLUSIONS: The present results suggest that females have a
      characteristic of allocating attention at an early stage when responding to faces
      actively (target) compared to viewing faces passively (non-target). This supports
      previous findings suggesting that task demand is an important factor in gender
      differences in N170.

PMID- 25857756
TI  - Investigation of the relationship between low environmental exposure to metals
      and bone mineral density, bone resorption and renal function.
AB  - Environmental exposure to metals has been linked to adverse health outcomes.
      Exposure to cadmium has been associated with decreased bone density, an increased
      risk of osteoporotic fracture and possible renal dysfunction. Older women are a
      group at risk of renal and bone density impacts and exposure to metals may be an
      important risk factor for these health outcomes. This study was a cross sectional
      study of 77 women aged 50 years and above examining the relationship between
      metals exposure and renal and bone health. Urinary and blood metals
      concentrations, plasma creatinine, iron, ferritin and transferrin were measured
      in these subjects. Bone biomarkers assessed included the pyridinium crosslinks,
      pyridinoline and deoxypyridinoline measured by ELISA. Renal function was assessed
      using eGFR and KIM-1. Whole body, hip and lumbar spine bone mineral density was
      assessed using DEXA. Blood and urinary metals concentrations were generally low
      in the subjects, with a median urinary cadmium concentration of 0.26 MUg/g
      creatinine (range <0.065-1.03 MUg/g). Urinary cadmium was found to be a
      significant predictor of bone mineral density at whole body, lumber spine, total
      hip and femoral neck, with increasing urinary Cd concentrations associated with
      decreased bone density. Urinary cadmium and aluminium concentrations were
      positively correlated with bone resorption whilst blood zinc and mercury
      concentrations were negatively correlated. Urinary aluminium was positively
      correlated with KIM-1 concentrations, a marker of early kidney damage, however
      blood zinc concentrations were significantly negatively correlated with this
      biomarker. This study provides additional support for low cadmium exposure being
      of concern for the health of older women. Further investigation into the role of
      exposure to other metals on bone and renal health is warranted.

PMID- 25857758
TI  - Erratum.
AB  - The original versions of Tables 1-4 that were contained in the article
      "International Retrospective Study of the Pipeline Embolization Device: A
      Multicenter Aneurysm Treatment Study" by D.F. Kallmes, R. Hanel, D. Lopes et al
      (AJNRAmJ Neuroradiol 2015;36:108-15, originally published on-line on October 29,
      2014, 10.3174/ajnr.A4111) contained errors. Due to a coding problem, 36 PICA and
      vertebral artery aneurysms were changed from "anterior" to "posterior." In
      addition, 17 ICA aneurysms were changed from "other anterior" to "ICA." The
      authors state that these changes do not affect the conclusions or clinical
      implications of their paper. The only outcome that changed in statistical
      significance was the comparison of the rates of neurologic mortality and
      neurologic morbidity + mortality between anterior and posterior circulation
      aneurysms at >30 days (Table 3). These are the corrected tables.

PMID- 25857757
TI  - Direct Cranial Nerve Involvement by Gliomas: Case Series and Review of the
      Literature.
AB  - Malignant gliomas are characterized by infiltrative growth of tumor cells,
      including along white matter tracts. This may result in clinical cranial
      neuropathy due to direct involvement of a cranial nerve rather than by
      leptomeningeal spread along cranial nerves. Gliomas directly involving cranial
      nerves III-XII are rare, with only 11 cases reported in the literature before
      2014, including 8 with imaging. We present 8 additional cases demonstrating
      direct infiltration of a cranial nerve by a glioma. Asymmetric cisternal nerve
      expansion compared with the contralateral nerve was noted with a mean length of
      involvement of 9.4 mm. Based on our case series, the key imaging feature for
      recognizing direct cranial nerve involvement by a glioma is the detection of an
      intra-axial mass in the pons or midbrain that is directly associated with
      expansion, signal abnormality, and/or enhancement of the adjacent cranial nerves.

PMID- 25857759
TI  - How Does the Accuracy of Intracranial Volume Measurements Affect Normalized Brain
      Volumes? Sample Size Estimates Based on 966 Subjects from the HUNT MRI Cohort.
AB  - BACKGROUND AND PURPOSE: The intracranial volume is commonly used for correcting
      regional brain volume measurements for variations in head size. Accurate
      intracranial volume measurements are important because errors will be propagated
      to the corrected regional brain volume measurements, possibly leading to biased
      data or decreased power. Our aims were to describe a fully automatic SPM-based
      method for estimating the intracranial volume and to explore the practical
      implications of different methods for obtaining the intracranial volume and
      normalization methods on statistical power. MATERIALS AND METHODS: We describe a
      method for calculating the intracranial volume that can use either T1-weighted or
      both T1- and T2-weighted MR images. The accuracy of the method was compared with
      manual measurements and automatic estimates by FreeSurfer and SPM-based methods.
      Sample size calculations on intracranial volume-corrected regional brain volumes
      with intracranial volume estimates from FreeSurfer, SPM, and our proposed method
      were used to explore the benefits of accurate intracranial volume estimates.
      RESULTS: The proposed method for estimating the intracranial volume compared
      favorably with the other methods evaluated here, with mean and absolute
      differences in manual measurements of -0.1% and 2.2%, respectively, and an
      intraclass correlation coefficient of 0.97 when using T1-weighted images. Using
      both T1- and T2-weighted images for estimating the intracranial volume slightly
      improved the accuracy. Sample size calculations showed that both the accuracy of
      intracranial volume estimates and the method for correcting the regional volume
      measurements affected the sample size. CONCLUSIONS: Accurate intracranial volume
      estimates are most important for ratio-corrected regional brain volumes, for
      which our proposed method can provide increased power in intracranial volume
      corrected regional brain volume data.

PMID- 25857760
TI  - Early MRI Characteristics after MRI-Guided Laser-Assisted Cingulotomy for
      Intractable Pain Control.
AB  - BACKGROUND AND PURPOSE: Cingulotomy is a well-accepted stereotactic procedure in
      the treatment of debilitating pain syndromes. At our institution, we used a 980
      nm diode laser to perform MR imaging-guided laser-assisted cingulotomy. We report
      the early MR imaging changes associated with this technique. MATERIALS AND
      METHODS: In this retrospective analysis, MR imaging-guided laser-assisted
      cingulotomy was performed in 4 patients with intractable pain secondary to
      metastatic disease. Patients were imaged at various time points postprocedure,
      with visual analysis of MR imaging changes in the cingulate gyri during that
      timeframe. RESULTS: Twenty-four hours postablation, 4 distinct zones of
      concentric rings reminiscent of an "owl eye" shape were noted in the cingulate
      gyri. Extrapolating from the imaging characteristics of the rings, we defined
      each zone as follows: The central zone (zone 1) represents a laser probe void
      with fluid, zones 2 and 3 have signal characteristics that represent hemorrhage
      and leaked protein, and zone 4 has a peripheral ring of acute infarction,
      enhancement, and surrounding edema. One patient with 1-year follow-up showed
      persistent concentric rings with resolution of enhancement and edema.
      CONCLUSIONS: Post-MR imaging-guided laser-assisted cingulotomy rings appear to
      represent a continuum of injury created by the laser probe and thermal injury.
      The imaging changes are similar to those described for laser ablation of tumor
      infiltrated brain with a 1064-nm laser. This is the first study to characterize
      early MR imaging changes after MR imaging-guided laser-assisted cingulotomy by
      using a 980-nm laser. It is important for neuroradiologists and neurosurgeons to
      understand expected imaging findings as laser ablation cingulotomy re-emerges to
      treat intractable pain.

PMID- 25857761
TI  - Application of a Novel Brain Arteriovenous Malformation Endovascular Grading
      Scale for Transarterial Embolization.
AB  - BACKGROUND AND PURPOSE: The advent of modern neuroendovascular techniques has
      highlighted the need for a simple, effective, and reliable brain arteriovenous
      malformation endovascular grading scale. A novel scale of this type has recently
      been described. It incorporates the number of feeding arteries, eloquence, and
      the presence of an arteriovenous fistula component. Our aim is to assess the
      validity of this grading scale. MATERIALS AND METHODS: We retrospectively
      reviewed all suspected brain arteriovenous malformations at Massachusetts General
      Hospital from 2005 to 2013, identifying 126 patients who met the inclusion
      criteria. Spearman correlations between endovascular and Spetzler-Martin grading
      scales and long-term outcomes were performed. Median endovascular grades were
      compared between treatment modalities and endovascular outcomes. Binary
      regression analysis was performed with major endovascular complications as a
      dichotomized dependent variable. Intraclass correlation coefficients were
      calculated for interobserver reliability of the endovascular grading scale.
      RESULTS: A significant Spearman correlation between the endovascular grade and
      the Spetzler-Martin grade was demonstrated (rho = 0.5, P < .01). Differences in
      the median endovascular grades between the endovascular cure (median = 2) and
      endovascular complication groups (median = 4) (P < .05) and between the
      endovascular cure and successful multimodal treatment groups (median = 3) (P <
      .05) were demonstrated. The endovascular grade was the only independent predictor
      of complications (OR = 0.5, P < .01). The intraclass correlation coefficient of
      the endovascular grade was 0.71 (P < .01). CONCLUSIONS: Validation of a brain
      arteriovenous malformation endovascular grading scale demonstrated that
      endovascular grades of <=II were associated with endovascular cure, while
      endovascular grades of <=III were associated with multimodal cure or significant
      lesion reduction and favorable outcome. The endovascular grade provides useful
      information to refine risk stratification for endovascular and multimodal
      treatment.

PMID- 25857764
TI  - Simultaneous Deletion of RAS Negative Feedback Genes Promotes AML.

PMID- 25857767
TI  - Vascular cell adhesion molecule-1, but not intercellular adhesion molecule-1, is
      associated with diabetic kidney disease in Asians with type 2 diabetes.
AB  - BACKGROUND AND AIMS: The association of adhesion molecules ICAM-1 and VCAM-1 with
      cardiovascular diseases has been well-studied. However, their roles in diabetic
      kidney disease (DKD) are incompletely understood. We aim to study the association
      of plasma ICAM-1 and VCAM-1 with DKD in Asians with type 2 diabetes (T2DM).
      SUBJECTS AND METHODS: A total of 1950 Asians with T2DM were included in this
      cross-sectional study. Plasma ICAM-1 and VCAM-1 were measured by immunoassays.
      RESULTS: Renal filtration function (eGFR) declined and urinary albumin-to
      creatinine ratio (ACR) levels increased progressively with the increase in plasma
      VCAM-1 levels. In contrast, no significant changes in eGFR and ACR were observed
      in subjects across different plasma ICAM-1 levels. Both ICAM-1 and VCAM-1 were
      correlated with ACR (rho = 0.153, p < 0.001 for VCAM-1 and ACR; rho = 0.053, p =
      0.020 for ICAM-1 and ACR) in bivariate correlation analysis. However, only VCAM-1
      was correlated with eGFR (rho = -0.228, p < 0.001). Multivariable linear
      regression models revealed that VCAM-1, but not ICAM-1, was independently
      associated with eGFR and albuminuria. Backward linear regression suggested that
      plasma VCAM-1 variability was mainly determined by eGFR whereas plasma ICAM-1
      level was mainly determined by C-reactive protein in patients with T2DM.
      CONCLUSIONS: Plasma VCAM-1 level, but not ICAM-1 level, was independently
      associated with prevalent DKD in Asians with T2DM. High level of ICAM-1 may be
      indicative of systemic inflammation and portends increase risk of incipient DKD.

PMID- 25857768
TI  - Regeneration of magnetic biochar derived from eucalyptus leaf residue for
      lead(II) removal.
AB  - Regeneration of Pb-loaded magnetic biochar prepared with eucalypts leaf residue
      was studied by using EDTA-2Na as a regenerant. The desorption efficiency was
      found to be 84.1% in 120 min with iron leaching amount of 1.1 mg g(-1). Higher
      SBET and pore volume were observed in regenerated magnetic biochars and no
      significant band shifts occurred in FTIR spectra during 6 regeneration cycles.
      The decrease of Pb(II) adsorption capacity (from 52.4 to 41.5 mg g(-1)) was only
      found in the first regeneration cycle. Magnetic separation performance of
      adsorbents was not significantly affected by multiple regeneration cycles.

PMID- 25857769
TI  - Repeated ethanol production from sweet sorghum juice concentrated by membrane
      separation.
AB  - Sequential batch fermentation from sweet sorghum juice concentrated by membrane
      separation (ultrafiltration permeation and nanofiltration concentration) to
      increase sugar contents, was investigated. Ethanol production at 5th batch
      fermentation by Saccharomyces cerevisiae BY4741 attained 113.7+/-3.1 g L(-1)
      (89.1+/-2.2% of the theoretical ethanol yield) from 270.0+/-22.6 g L(-1) sugars,
      corresponding to 98.7% of ethanol titer attained at the 1st batch fermentation.
      This titer was comparable to ethanol production of 115.8+/-0.6 g L(-1) (87.1+/
      2.7% of the theoretical ethanol yield) obtained at 5th batch fermentation with 3
      g L(-1) yeast extract and 6 g L(-1) polypeptone. Increase of cell density in the
      concentrated sweet sorghum juice was observed during sequential batch
      fermentation, as indicated by increased OD600. Utilization of sweet sorghum juice
      as the sole source, membrane separation, and S. cerevisiae was a cost-effective
      process for high ethanol production.

PMID- 25857770
TI  - Membrane-permeable tastants amplify beta2-adrenergic receptor signaling and delay
      receptor desensitization via intracellular inhibition of GRK2's kinase activity.
AB  - BACKGROUND: Amphipathic sweet and bitter tastants inhibit purified forms of the
      protein kinases GRK2, GRK5 and PKA activities. Here we tested whether membrane
      permeable tastants may intracellularly interfere with GPCR desensitization at the
      whole cell context. METHODS: beta2AR-transfected cells and cells containing
      endogenous beta2AR were preincubated with membrane-permeable or impermeable
      tastants and then stimulated with isoproterenol (ISO). cAMP formation, beta2AR
      phosphorylation and beta2AR internalization were monitored in response to ISO
      stimulation. IBMX and H89 inhibitors and GRK2 silencing were used to explore
      possible roles of PDE, PKA, and GRK2 in the tastants-mediated amplification of
      cAMP formation and the tastant delay of beta2AR phosphorylation and
      internalization. RESULTS: Membrane-permeable but not impermeable tastants
      amplified the ISO-stimulated cAMP formation in a concentration- and time
      dependent manner. Without ISO stimulation, amphipathic tastants, except caffeine,
      had no effect on cAMP formation. The amplification of ISO-stimulated cAMP
      formation by the amphipathic tastants was not affected by PDE and PKA activities,
      but was completely abolished by GRK2 silencing. Amphipathic tastants delayed the
      ISO-induced GRK-mediated phosphorylation of beta2ARs and GRK2 silencing abolished
      it. Further, tastants also delayed the ISO-stimulated beta2AR internalization.
      CONCLUSION: Amphipathic tastants significantly amplify beta2AR signaling and
      delay its desensitization via their intracellular inhibition of GRK2. GENERAL
      SIGNIFICANCE: Commonly used amphipathic tastants may potentially affect similar
      GPCR pathways whose desensitization depends on GRK2's kinase activity. Because
      GRK2 also modulates phosphorylation of non-receptor components in multiple
      cellular pathways, these gut-absorbable tastants may permeate into various cells,
      and potentially affect GRK2-dependent phosphorylation processes in these cells as
      well.

PMID- 25857771
TI  - Expression in yeast, new substrates, and construction of a first 3D model of
      human orphan cytochrome P450 2U1: Interpretation of substrate hydroxylation
      regioselectivity from docking studies.
AB  - BACKGROUND: Cytochrome P450 2U1 (CYP2U1) has been identified from the human
      genome and is highly conserved in the living kingdom. In humans, it has been
      found to be predominantly expressed in the thymus and in the brain. CYP2U1 is
      considered as an "orphan" enzyme as few data are available on its physiological
      function(s) and active site topology. Its only substrates reported so far were
      unsaturated fatty acids such as arachidonic acid, and, much more recently, N
      arachidonoylserotonin. METHODS: We expressed CYP2U1 in yeast Saccharomyces
      cerevisiae, built a 3D homology model of CYP2U1, screened a library of compounds
      known to be substrates of CYP2 family with metabolite detection by high
      performance liquid chromatography-mass spectrometry, and performed docking
      experiments to explain the observed regioselectivity of the reactions. RESULTS:
      We show that drug-related compounds, debrisoquine and terfenadine derivatives,
      subtrates of CYP2D6 and CYP2J2, are hydroxylated by recombinant CYP2U1 with
      regioselectivities different from those reported for CYP2D6 and 2J2. Docking
      experiments of those compounds and of arachidonic acid allow us to explain the
      regioselectivity of the hydroxylations on the basis of their interactions with
      key residues of CYP2U1 active site. MAJOR CONCLUSION: Our results show for the
      first time that human orphan CYP2U1 can oxidize several exogenous molecules
      including drugs, and describe a first CYP2U1 3D model. GENERAL SIGNIFICANCE:
      These results could have consequences for the metabolism of drugs particularly in
      the brain. The described 3D model should be useful to identify other substrates
      of CYP2U1 and help in understanding its physiologic roles.

PMID- 25857772
TI  - Inhibitory effect of ephedrannins A and B from roots of Ephedra sinica STAPF on
      melanogenesis.
AB  - BACKGROUND: Melanogenesis, a process producing the pigment melanin in human skin,
      eyes and hair, is a major physiological response against various environmental
      stresses, in particular exposure to ultraviolet radiation, and its pathway is
      regulated by a key enzyme, tyrosinase. In this study, we evaluated the effects of
      ephedrannins A and B, which are polyphenols from the roots of Ephedra sinica,
      commonly used in herbalism in oriental countries, on mushroom tyrosinase and
      melanogenesis in B16F10 melanoma cells. METHODS: Their effects on mushroom
      tyrosinase were determined via kinetic studies using a spectrophotometric
      analysis and those on melanin and tyrosinase production in melanoma cells treated
      with alpha-MSH (melanin stimulating hormone) were examined using PCR and ELISA.
      RESULTS: Both ephedrannins A and B exhibited concentration-dependent inhibitory
      effects on L-tyrosine oxidation by mushroom tyrosinase, and the inhibition
      mechanism was competitive and reversible with L-tyrosine as the substrate. In
      addition, melanin production in melanoma cells was also suppressed in a
      concentration-dependent manner by ephedrannins A and B without significant
      effects on cell proliferation at the concentrations tested. Both compounds showed
      inhibitory effects on melanin production by suppressing the transcription of
      tyrosinase in the cells. CONCLUSION: Both compounds exhibited significant
      inhibitory effects, but the inhibition by ephedrannin B was much more effective
      than that by ephedrannin A. Both ephedrannins A and B may be good candidates for
      a whitening agent for skin. GENERAL SIGNIFICANCE: This is the first report that
      describes effective inhibition of melanin production by ephedrannins A and B
      isolated from Ephedra roots.

PMID- 25857773
TI  - IMP-GMP specific cytosolic 5'-nucleotidase regulates nucleotide pool and prodrug
      metabolism.
AB  - BACKGROUND: Type II cytosolic 5'-nucleotidase (cN-II) catalyzes the hydrolysis of
      purine and, to some extent, of pyrimidine monophosphates. Recently, a number of
      papers demonstrated the involvement of cN-II in the mechanisms of resistance to
      antitumor drugs such as cytarabine, gemcitabine and fludarabine. Furthermore, cN
      II is involved in drug resistance in patients affected by hematological
      malignancies influencing the clinical outcome. Although the implication of cN-II
      expression and/or activity appears to be correlated with drug resistance and poor
      prognosis, the molecular mechanism by which cN-II mediates drug resistance is
      still unknown. METHODS: HEK 293 cells carrying an expression vector coding for cN
      II linked to green fluorescent protein (GFP) and a control vector without cN-II
      were utilized. A highly sensitive capillary electrophoresis method was applied
      for nucleotide pool determination and cytotoxicity exerted by drugs was
      determined with 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide
      (MTT) assay. RESULTS: Over-expression of cN-II causes a drop of nucleoside
      triphosphate concentration and a general disturbance of nucleotide pool. Over
      expressing cells were resistant to fludarabine, gemcitabine and cytarabine
      independently of cN-II ability to hydrolyze their monophosphates. CONCLUSIONS: An
      increase of cN-II expression is sufficient to cause both a general disturbance of
      nucleotide pool and an increase of half maximal inhibitory concentration (IC50)
      of the drugs. Since the monophosphates of cytarabine and gemcitabine are not
      substrates of cN-II, the protection observed cannot be directly ascribed to drug
      inactivation. GENERAL SIGNIFICANCE: Our results indicate that cN-II exerts a
      relevant role in nucleotide and drug metabolism through not only enzyme activity
      but also a mechanism involving a protein-protein interaction, thus playing a
      general regulatory role in cell survival. SENTENCE: Resistance to fludarabine,
      gemcitabine and cytarabine can be determined by an increase of cN-II both through
      dephosphorylation of active drugs and perturbation of nucleotide pool.

PMID- 25857774
TI  - Spotlight on prostate cancer: the latest evidence and current controversies.
AB  - Recent decades have seen dramatic changes in the management of prostate cancer
      based on novel research findings. Prostate-specific antigen (PSA) screening has
      been introduced, and then recently modified to include new strategies and
      biomarkers. Management of advanced disease has been transformed by the rapid
      introduction of new agents. We have moved from a "one-size-fits-all" approach in
      prostate cancer management to multidisciplinary strategies tailored to the
      individual patient and his specific cancer. This editorial marks the launch of
      the article collection Spotlight on prostate cancer
      (http://www.biomedcentral.com/bmcmed/series/SPR), and here, guest editors Sigrid
      Carlsson and Andrew Vickers give an overview of the past, present, and future of
      prostate cancer research and management. 

PMID- 25857775
TI  - Engineering Escherichia coli for functional expression of membrane proteins.
AB  - A major bottleneck in the characterization of membrane proteins is low yield of
      functional protein in recombinant expression. Microorganisms are widely used for
      recombinant protein production, because of ease of cultivation and high protein
      yield. However, the target proteins do not always obtain their native
      conformation and may end up in a nonfunctional state, in insoluble aggregates.
      For screening of functional protein, it is thus important to readily discriminate
      aggregated, mistargeted protein from globally well-folded, membrane-inserted
      protein. We developed a robust strategy for expression screening of functional
      proteins in bacteria, which is based on directed evolution. In this strategy, the
      C-terminus of the target membrane protein is tagged with two additional protein
      domains in tandem. The first one is green fluorescent protein (GFP), which
      functions as a reporter of the global folding state of the fusion protein. The
      other one is the erythromycin resistance protein (23S ribosomal RNA adenine N-6
      methyltransferase, ErmC), which confers a means to select for enhanced
      expression. By gradually increasing the antibiotic concentration in the medium,
      we force the cells to evolve in a way that allows more functional target-GFP-ErmC
      to be expressed. The acquired genomic mutations can be generic or membrane
      protein specific. This strategy is readily adopted for the expression of any
      protein and ultimately yields a wealth of genomic data that may provide insight
      into the factors that limit the production of given classes or types of proteins.

PMID- 25857776
TI  - ACEMBLing a multiprotein transmembrane complex: the functional SecYEG-SecDF-YajC
      YidC Holotranslocon protein secretase/insertase.
AB  - Membrane proteins constitute about one third of the proteome. The ubiquitous Sec
      machinery facilitates protein movement across or integration of proteins into the
      cytoplasmic membrane. In Escherichia coli post- and co-translational targeting
      pathways converge at the protein-conducting channel, consisting of a central
      pore, SecYEG, which can recruit accessory domains SecDF-YajC and YidC, to form
      the holotranslocon (HTL) supercomplex. Detailed analysis of HTL function and
      architecture remained elusive until recently, largely due to the lack of a
      purified, recombinant complex. ACEMBL is an advanced DNA recombineering-based
      expression vector system we developed for producing challenging multiprotein
      complexes. ACEMBL affords the means to combine multiple expression elements
      including promoter DNAs, tags, genes of interest, and terminators in a
      combinatorial manner until optimal multigene expression plasmids are constructed
      that yield correctly assembled, homogenous, and active multiprotein complex
      specimens. We utilized ACEMBL for recombinant HTL overproduction. We developed
      protocols for detergent solubilizing and purifying the HTL. Highly purified
      complex was then used to reveal HTL function and the interactions between its
      constituents. HTL activity in protein secretion and membrane protein insertion
      was analyzed in both the presence and absence of the proton-motive force. Setting
      up ACEMBL for the assembly of multigene expression constructs that achieve high
      yields of functional multisubunit membrane protein complex is straightforward.
      Here, we used ACEMBL for obtaining active HTL supercomplex in high quality and
      quantity. The concept can likewise be applied to obtain many other assemblies of
      similar complexity, by overexpression in prokaryotic, and also eukaryotic hosts. 

PMID- 25857777
TI  - Expression and purification of OsVDAC4.
AB  - The voltage-dependent anion channel (VDAC), a major component of the
      mitochondrial outer membrane, has emerged as an important player in cell
      function, survival, and death signaling. VDAC function is modulated by its
      interaction with proteins such as hexokinase, adenine nucleotide translocator,
      and apoptotic proteins like Bax. Monitoring the activity of VDAC and its
      modulation in the complex cellular milieu is fraught with complications.
      Minimizing the number of components in the study is one approach to teasing apart
      various aspects of its function. In this chapter, we have described detailed
      protocols for the purification of a rice VDAC isoform, OsVDAC4 after
      overexpression in a bacterial system. The protein is solubilized with LDAO and
      then reconstituted into liposomes or planar bilayers to verify its competence to
      fold into a functionally active form. 

PMID- 25857778
TI  - Membrane protein expression in Lactococcus lactis.
AB  - The Gram-positive bacterium Lactococcus lactis has many properties that are ideal
      for the overproduction of membrane proteins in a functional form. Growth of
      lactococci is rapid, proceeds to high cell densities, and does not require
      aeration, which facilitates large-scale fermentation. The available promoter
      systems are strong and tightly regulated, allowing expression of toxic gene
      products in a controlled manner. Expressed membrane proteins are targeted
      exclusively to the cytoplasmic membrane, allowing the use of ionophores, ligands,
      and inhibitors to study activity of the membrane protein in whole cells.
      Constructed plasmids are stable and expression levels are highly reproducible.
      The relatively small genome size of the organism causes little redundancy, which
      facilitates complementation studies and allows for easier purification. The
      produced membrane proteins are often stable, as the organism has limited
      proteolytic capability, and they are readily solubilized from the membrane with
      mild detergents. Lactococci are multiple amino acid auxotrophs, allowing the
      incorporation of labels, such as selenomethionine. Among the few disadvantages
      are the low transformation frequency, AT-rich codon usage, and resistance to
      lysis by mechanical means, but these problems can be overcome fairly easily. We
      will describe in detail the protocols used to express membrane proteins in L.
      lactis, from cloning of the target gene to the isolation of membrane vesicles for
      the determination of expression levels. 

PMID- 25857779
TI  - An unconventional anaerobic membrane protein production system based on Wolinella
      succinogenes.
AB  - In cases where membrane protein production attempts in more conventional
      Escherichia coli-based systems have failed, a solution is to resort to a system
      based on the nonpathogenic epsilon-proteobacterium Wolinella succinogenes. This
      approach has been demonstrated to be successful for structural and mechanistic
      analyses not only for homologous production of W. succinogenes membrane proteins
      but also for the heterologous production of membrane protein complexes from the
      human pathogens Helicobacter pylori and Campylobacter jejuni. The procedure to
      establish a system for the production of native and variant enzymes in W.
      succinogenes is presented in detail for the examples of the quinol:fumarate
      reductase and the SdhABE complexes of W. succinogenes. Subsequently, further
      projects using W. succinogenes as expression host are covered. 

PMID- 25857780
TI  - Membrane protein expression and analysis in yeast.
AB  - This protocol describes the expression and analysis of membrane proteins produced
      in yeast, as illustrated with Yarrowia lipolytica and Pichia pastoris. Step by
      step, we explain how to generate a yeast strain expressing the membrane protein
      of interest, how to prepare a membrane protein sample from yeast, and how to
      analyze the expression levels using SDS-PAGE and Western blotting. In the final
      section, we describe how to perform a radioligand binding assay, which quantifies
      the amount of the protein folded in a ligand-binding competent state. 

PMID- 25857781
TI  - Heterologous expression of G-protein-coupled receptors in yeast.
AB  - Heterologous yeast expression systems have been successfully used for the
      production of G-protein-coupled receptors (GPCRs) for both structural and
      functional studies. Yeast combine comparatively low cost and short culture times
      with straightforward generation of expression clones. They also perform some key
      posttranslational modifications not possible in bacterial systems. There are two
      major yeast expression systems, Pichia pastoris and Saccharomyces cerevisiae,
      both of which have been used for the production of GPCRs. P. pastoris has a
      proven track record for the production of large amounts of GPCR for structural
      studies. High-resolution crystal structures of both the adenosine A2A and the
      histamine H1 receptors have been obtained using protein expressed in this system.
      S. cerevisiae is relatively easy to engineer and this has resulted in the
      development of sophisticated tools for the functional characterization of GPCRs.
      In this chapter, we provide protocols for both large-scale receptor expression in
      P. pastoris for structural studies and small-scale receptor expression in S.
      cerevisiae for functional characterization. In both cases, the receptor used is
      the human adenosine A2A receptor. The results that both we and others have
      obtained using these protocols show the wide utility of the yeast expression
      systems for the production of GPCRs. 

PMID- 25857782
TI  - Recombinant G protein-coupled receptor expression in Saccharomyces cerevisiae for
      protein characterization.
AB  - G protein-coupled receptors (GPCRs) are membrane proteins that mediate signaling
      across the cellular membrane and facilitate cellular responses to external
      stimuli. Due to the critical role that GPCRs play in signal transduction,
      therapeutics have been developed to influence GPCR function without an extensive
      understanding of the receptors themselves. Closing this knowledge gap is of
      paramount importance to improving therapeutic efficacy and specificity, where
      efforts to achieve this end have focused chiefly on improving our knowledge of
      the structure-function relationship. The purpose of this chapter is to review
      methods for the heterologous expression of GPCRs in Saccharomyces cerevisiae,
      including whole-cell assays that enable quantitation of expression, localization,
      and function in vivo. In addition, we describe methods for the micellular
      solubilization of the human adenosine A2a receptor and for reconstitution of the
      receptor in liposomes that have enabled its biophysical characterization. 

PMID- 25857783
TI  - Baculovirus-mediated expression of GPCRs in insect cells.
AB  - G-protein-coupled receptors (GPCRs) are a large family of seven transmembrane
      proteins that influence a considerable number of cellular events. For this
      reason, they are one of the most studied receptor types for their pharmacological
      and structural properties. Solving the structure of several GPCR receptor types
      has been possible using almost all expression systems, including Escherichia
      coli, yeast, mammalian, and insect cells. So far, however, most of the GPCR
      structures solved have been done using the baculovirus insect cell expression
      system. The reason for this is mainly due to cost-effectiveness,
      posttranslational modification efficiency, and overall effortless maintenance.
      The system has evolved so much that variables starting from vector type,
      purification tags, cell line, and growth conditions can be varied and optimized
      countless ways to suit the needs of new constructs. Here, we present the array of
      techniques that enable the rapid and efficient optimization of expression steps
      for maximal protein quality and quantity, including our emendations. 

PMID- 25857784
TI  - Expression of membrane proteins in the eyes of transgenic Drosophila
      melanogaster.
AB  - In recent years, improved protein expression and crystallization strategies, as
      well as advanced synchrotron radiation sources and crystallographic tools
      considerably increased the number of crystal structures of integral membrane
      proteins from higher eukaryotes. However, seen as a proportion of the total
      number of candidate proteins, these achievements still appear meager, reflecting
      the huge effort that is often required to obtain high-level and functional
      expression of eukaryotic membrane proteins. Besides bacteria, yeast, insect, or
      mammalian cells are frequently used for heterologous expression, but despite
      considerable investments in time, labor, and money, there are numerous drawbacks
      to these systems. Are there other strategies that allow for an effective, large
      scale production of functional membrane proteins? This chapter describes the
      expression of proteins in photoreceptor cells of transgenic Drosophila as an
      easily accessible, versatile alternative. We present step-by-step protocols
      starting from the cloning of the target gene into a suitable vector for fly eye
      expression and ending with the harvest of transgenic Drosophila and subsequent
      protein purification from the eye. Our examples span a number of eukaryotic
      membrane proteins from different classes-including receptors, transporters,
      channels, and enzymes-that were successfully expressed without further
      optimization. The protocols provided here are robust and straightforward to
      follow even without prior experience in Drosophila work. 

PMID- 25857785
TI  - Rapid method to express and purify human membrane protein using the Xenopus
      oocyte system for functional and low-resolution structural analysis.
AB  - Progress toward elucidating the 3D structures of eukaryotic membrane proteins has
      been hampered by the lack of appropriate expression systems. Recent work using
      the Xenopus oocyte as a novel expression system for structural analysis
      demonstrates the capability of providing not only the significant amount of
      protein yields required for structural work but also the expression of eukaryotic
      membrane proteins in a more native and functional conformation. There is a long
      history using the oocyte expression system as an efficient tool for membrane
      transporter and channel expression in direct functional analysis, but
      improvements in robotic injection systems and protein yield optimization allow
      the rapid scalability of expressed proteins to be purified and characterized in
      physiologically relevant structural states. Traditional overexpression systems
      (yeast, bacteria, and insect cells) by comparison require chaotropic conditions
      over several steps for extraction, solubilization, and purification. By contrast,
      overexpressing within the oocyte system for subsequent negative-staining
      transmission electron microscopy studies provides a single system that can
      functionally assess and purify eukaryotic membrane proteins in fewer steps
      maintaining the physiological properties of the membrane protein. 

PMID- 25857786
TI  - Expression of G protein-coupled receptors in Mammalian cells.
AB  - G protein-coupled receptors (GPCRs) are cell surface proteins and play crucial
      role in mediating effective communication between extracellular and intracellular
      milieu of the cell. To understand the structure and function of these membrane
      proteins, it is imperative to express the proteins in a functional form and in
      sufficient quantities. However, heterologous expression of GPCRs in sufficient
      amounts for structural studies is a daunting task and over the years researchers
      have tried various expression systems to achieve this goal. Here, we describe a
      method developed in the laboratory of Dr. Har Gobind Khorana and successfully
      used over the past decade to express GPCRs and other membrane proteins in
      mammalian cells. Improvements to this method include use of genes codon optimized
      for expression in mammalian cells, use of expression tags at N-terminus, and
      affinity tags at the N-terminus and C-terminus of GPCRs. It also provides details
      for the process of selection for stably transfected clones, and to identify
      clones that are effectively expressing the GPCR of interest on the cell surface
      using flow cytometry. Purification of the overexpressed GPCR involves use of
      affinity chromatography. The method discussed here can also be effectively used
      to express cytotoxic proteins such as some constitutively active GPCRs. The
      method is robust and reliable to express GPCRs. 

PMID- 25857787
TI  - Construction of stable mammalian cell lines for inducible expression of G protein
      coupled receptors.
AB  - The large-scale expression of many membrane proteins, including the members of
      the G protein-coupled receptor superfamily, in a correctly folded and fully
      functional form remains a formidable challenge. In this chapter, we focus on the
      construction of stable mammalian cell lines to overcome this hurdle. First, we
      will outline the steps for establishing a tightly regulated gene expression
      system in human HEK293S cells. This system utilizes separate plasmids containing
      components of well-defined genetic control elements from the Escherichia coli
      tetracycline operon to control the powerful cytomegalovirus immediate early
      enhancer/promoter. Next, we describe the assembly of this expression system into
      HEK293S cells and a derivative cell line devoid of complex N-glycosylation.
      Finally, we describe methods for the growth of these cells lines in scalable
      suspension culture for the preparation of milligram amounts of recombinant
      protein. 

PMID- 25857788
TI  - Rapid and facile recombinant expression of bovine rhodopsin in HEK293S GnTI(-)
      cells using a PiggyBac inducible system.
AB  - Rhodopsin is a class A G protein-coupled receptor (GPCR) that provides important
      insights into the structure and function of the GPCR superfamily. Bovine
      rhodopsin is widely used as a model for GPCRs and was the first GPCR whose X-ray
      crystal structure was solved. One of the advantages of rhodopsin is that it is
      abundant in native tissue, and as a result, milligram quantities can be purified
      from the retinal rod cells of bovine eyes. Nonetheless, the study of GPCR
      conformation and dynamics, e.g., by electron paramagnetic resonance or (19)F
      nuclear magnetic resonance spectroscopy, typically requires mutagenesis to enable
      site-directed labeling of the protein. Mutations are also of great importance as
      they can stabilize the receptor and can be necessary to study different receptor
      conformations. Recombinant production of rhodopsins for biophysical studies has
      been achieved in different systems, including mammalian, insect, and yeast cells
      in culture, and from Drosophila melanogaster and Caenorhabditis elegans tissue.
      The piggyBac (PB) transposon system is used for gene delivery into a variety of
      cell types (e.g., HEK293 and CHO cells, fibroblasts, stem cells) and living
      organisms (e.g., honeybees, pigs, chicken, mice). Recently, the PB transposon has
      been described as an efficient tool for inducible protein expression in HEK293T
      and HEK293S N-acetylglucosaminyltransferase I-deficient (GnTI(-)) cells. This
      chapter describes a protocol for using the PB-based system for inducible
      expression of bovine rhodopsin in HEK293S GnTI(-) cells. Using this protocol, we
      expressed and purified 26 rhodopsin mutants to be used for site-directed spin
      labeling. 

PMID- 25857789
TI  - Semliki forest virus-based expression of recombinant GPCRs.
AB  - Due to their importance as targets for drug development, rapid and consistent
      high-level production of G protein-coupled receptors (GPCRs) has become an
      essential part of drug discovery. Alphaviruses, particularly recombinant Semliki
      Forest virus (SFV) particles, have provided the means for expression of a number
      of GPCRs in a broad range of mammalian host cell lines for pharmacological
      characterization by determination of receptor binding activity and functional
      coupling to G proteins. The rapid high-titer virus particle production has made
      it possible to study a large number of GPCRs in parallel. Moreover, large-scale
      production in adherent and suspension cultures of mammalian cells has provided
      sufficient amounts of GPCRs for purification and subsequent structural studies.
      Furthermore, the high preference for neuronal delivery of SFV particles has
      allowed functional and localization studies of recombinant proteins in
      hippocampal slice cultures, in primary neurons, and in vivo. 

PMID- 25857790
TI  - Screening for lipid requirements of membrane proteins by combining cell-free
      expression with nanodiscs.
AB  - Cell-free (CF) protein expression has emerged as one of the most efficient
      production platforms for membrane proteins. Central bottlenecks prevalent in
      conventional cell-based expression systems such as mistargeting, inclusion body
      formation, degradation as well as product toxicity can be addressed by taking
      advantage of the reduced complexity of CF expression systems. However, the open
      accessibility of CF reactions offers the possibility to design customized
      artificial expression environments by supplying synthetic hydrophobic compounds
      such as micelles or membranes of defined composition. The open nature of CF
      systems therefore generally allows systematic screening approaches for the
      identification of efficient cotranslational solubilization environments of
      membrane proteins. Synergies exist in particular with the recently developed
      nanodisc (ND) technology enabling the synthesis of stable and highly soluble
      particles containing membrane discs of defined composition. Specific types of
      lipids frequently modulate folding, stability, and activity of integrated
      membrane proteins. One recently reported example are phospho-MurNAc-pentapeptide
      (MraY) translocases that catalyze a crucial step in bacterial peptidoglycan
      biosynthesis making them interesting as future drug targets. Production of
      functionally active MraY homologues from most human pathogens in conventional
      cellular production systems was so far not successful due to their obviously
      strict lipid dependency for functionally folding. We demonstrate that the
      combination of CF expression with ND technologies is an efficient strategy for
      the production of folded MraY translocases, and we present a general protocol for
      the rapid screening of lipid specificities of membrane proteins. 

PMID- 25857791
TI  - Liposome reconstitution and transport assay for recombinant transporters.
AB  - Secondary active transporters are responsible for the cellular uptake of many
      biologically important molecules, including neurotransmitters, nutrients, and
      drugs. Because of their physiological and clinical importance, a method for
      assessing their transport activity in vitro is necessary to gain a better
      understanding of how these transporters function at the molecular level. In this
      chapter, we describe a protocol for reconstituting the concentrative nucleoside
      transporter from Vibrio cholerae into proteoliposomes. We then describe a
      radiolabeled substrate uptake assay that can be used to functionally characterize
      the transporter. These methods are relatively common and can be applied to other
      secondary active transporters, with or without some modification. 

PMID- 25857792
TI  - Lipid reconstitution and recording of recombinant ion channels.
AB  - Ion channels are membrane proteins that facilitate passive ion movements down the
      electrochemical gradients across biological membranes. They regulate a wide range
      of important physiological functions, from neuronal excitation, muscle
      contraction, substance absorption in epithelial tissues, to innate immunity. In
      recent years, the membrane transport field has seen tremendous advances in
      membrane protein purification and structural determination. This paves the way
      for investigators to reconstitute ion channels into biochemically defined lipid
      systems free of other biological constituents and to study channel functions
      within a structural context. The goal of this chapter is to guide readers through
      the process of producing proteoliposomes, designing liposome assays for initial
      characterization of channel function, and performing electrical recordings for in
      depth mechanistic investigation. 

PMID- 25857793
TI  - Reconstitution of membrane proteins: a GPCR as an example.
AB  - Membrane proteins are the gatekeepers to the cell and are essential to the
      function of all cells, controlling the flow of molecules and information across
      the cell membrane. Much effort has been put into the development of systems for
      studying membrane proteins in simplified environments that nevertheless mimic
      their native lipid environment. After isolation and production of purified
      membrane proteins in detergent, it is often necessary to reconstitute them into a
      lipid structure such as liposome, nanodisc, or lipodisq. Each of these has the
      advantage of returning the protein to a defined lipid environment, and the choice
      of system depends on the application. Regardless of the system to be used, the
      fundamental process involves the removal of detergent and incorporation of the
      protein into a stable lipid system. This chapter details methodologies we have
      developed, mainly focussed on the model G protein-coupled receptor (GPCR)
      neurotensin receptor 1, and the GPCR-homologue and model, bacteriorhopdopsin. 

PMID- 25857794
TI  - Ion channel reporter for monitoring the activity of engineered GPCRs.
AB  - Ion channel-coupled receptor (ICCR) is a recent technology based on the fusion of
      G protein-coupled receptors (GPCRs) to an ion channel. Binding of ligands on the
      GPCR triggers conformational changes of the receptor that are mechanically
      transmitted to the ion channel gates, generating an electrical signal easily
      detectable with conventional electrophysiological techniques. ICCRs are
      heterologously expressed in Xenopus oocytes and offers several advantages such
      as: (i) real-time recordings on single cells, (ii) standard laboratory
      environment and inexpensive media for Xenopus oocytes maintenance, (iii) absence
      of protein purification steps, (iv) sensitivity to agonists and antagonists in
      concentration-dependent manner, (v) compatibility with a Gi/o protein activation
      assay based on Kir3.x channels, and (vi) ability to detect receptor activation
      independently of intracellular effectors. This last characteristic of ICCRs led
      to the development of a functional assay for G protein-"uncoupled" receptors such
      as GPCRs optimized for crystallization by alteration of their third intracellular
      (i3) loop. One of the most widely used approaches consists in replacing the i3
      loop with the T4 phage lysozyme (T4L) domain that obstructs the access of G
      proteins to their binding site. We recently demonstrated that the ICCR technology
      can functionally characterize GPCRs(T4L). Two-electrode voltage-clamp (TEVC)
      recordings revealed that apparent affinities and sensitivities to ligands are not
      affected by T4L insertion, while ICCRs(T4L) displayed a partial agonist phenotype
      upon binding of full agonists, suggesting that ICCRs could detect intermediate
      active states. This chapter aims to provide exhaustive details from molecular
      biology steps to electrophysiological recordings for the design and the
      characterization of ICCRs and ICCRs(T4L). 

PMID- 25857795
TI  - Methods for labeling skeletal muscle ion channels site-specifically with
      fluorophores suitable for FRET-based structural analysis.
AB  - Skeletal muscle excitation-contraction coupling is triggered by the concerted
      action of two enormous Ca(2+) channel complexes, the dihydropyridine receptor and
      the type 1 ryanodine receptor. Recent advances in our understanding of the
      structure of these large Ca(2+) channels have been driven by fluorescence
      resonance energy transfer (FRET)-based analysis. A methodological challenge in
      conducting these FRET measurements is the ability to site-specifically label
      these huge ion channels with donor and acceptor fluorophores capable of
      undergoing energy transfer. In this chapter, we detail specific protocols for
      tagging large membrane proteins with these fluorescent probes using three
      orthogonal labeling methods: fluorescent protein fusions, biarsenical reagents
      directed to engineered tetracysteine tags, and Cy3/5 nitrilotriacetic acid
      conjugates that bind to poly-histidine tags. 

PMID- 25857796
TI  - Structural and Functional Studies of NirC from Salmonella typhimurium.
AB  - NirC is a pentameric transport system for monovalent anions that is expressed in
      the context of assimilatory nitrite reductase NirBD in a wide variety of
      enterobacterial species. A NirC pentamer contains individual pores in each
      protomer that mediate the passage of at least the nitrite [Formula: see text] and
      nitrate [Formula: see text] anions. As a member of the formate/nitrite
      transporter family of membrane transport proteins, NirC shares a range of
      structural and functional features with the formate channel FocA and the
      hydrosulfide channel AsrD (HSC). NirC from the enteropathogen Salmonella
      typhimurium has been studied by X-ray crystallography, proton uptake assays, and
      different electrophysiological techniques, and the picture that has emerged shows
      a fast and versatile transport system for nitrite that doubles as a defense
      system during the enteric life of the bacterium. Structural and functional assays
      are described, which shed light on the transport mechanism of this important
      molecular machine. 

PMID- 25857797
TI  - Surface plasmon resonance analysis of seven-transmembrane receptors.
AB  - G-protein coupled receptors (GPCRs) are the primary target class of currently
      marketed drugs, accounting for around a third of all drug targets of approved
      medicines. However, almost all the screening efforts for novel ligand discovery
      rely exclusively on cellular systems overexpressing the receptors. Current
      receptor assay systems are based on measurement of either ligand displacement or
      downstream functional responses, rather than direct observation of ligand
      binding. Issues of allosteric modulation, probe dependence, and functional
      selectivity create challenges in selecting suitable assay formats. Therefore, a
      method that directly measures GPCR-ligand interactions, independent of binding
      site, probe, and signaling pathway would be a useful primary and orthogonal
      screening method. An alternative ligand discovery strategy would be the direct
      measurement of GPCR-ligand interactions by label-free technologies, such as
      surface plasmon resonance (SPR). In this chapter, we summarize overview of the
      SPR technology and development of applications for detection of ligand binding to
      GPCRs using wild-type and thermostabilized receptors. We discuss the utilization
      of SPR as a biophysical screening method for fragment-based drug discovery for
      GPCRs. In particular, we show how SPR screening can detect both orthosteric and
      allosteric ligands with the appropriate experimental design. 

PMID- 25857798
TI  - Cross-linking strategies to study peptide ligand-receptor interactions.
AB  - Experiments are described that allowed cross-linking of analogs of a 13-amino
      acid peptide into the binding site of a model G protein-coupled receptor.
      Syntheses of peptide analogs that were used for photochemical or chemical cross
      linking were carried out using solid-phase peptide synthesis. Chemical cross
      linking utilized 3,4-dihydroxy-l-phenylalanine-incorporated peptides and
      subsequent periodate-mediated activation, whereas photochemical cross-linking was
      mediated by p-benzoyl-l-phenylalanine (Bpa)-labeled peptides and UV-initiated
      activation. Mass spectrometry was employed to locate the site(s) in the receptor
      that formed the cross-links to the ligand. We also describe a method called
      unnatural amino acid replacement that allowed capture of a peptide ligand into
      the receptor. In this method, the receptor was genetically modified by
      replacement of a natural amino acid with Bpa. The modified receptor was UV
      irradiated to capture the ligand. The approaches described are applicable to
      other peptide-binding proteins and can reveal the ligand-binding site in atomic
      detail. 

PMID- 25857799
TI  - From Recombinant Expression to Crystals: A Step-by-Step Guide to GPCR
      Crystallography.
AB  - G protein-coupled receptors (GPCRs) are the primary targets of drugs prescribed
      for many human pathophysiological conditions such as hypertension, allergies,
      schizophrenia, asthma, and various types of cancer. High-resolution structure
      determination of GPCRs has been a key focus area in GPCR biology to understand
      the basic mechanism of their activation and signaling and to materialize the long
      standing dream of structure-based drug design on these versatile receptors. There
      has been tremendous effort at this front in the past two decades and it has
      culminated into crystal structures of 27 different receptors so far. The recent
      progress in crystallization and structure determination of GPCRs has been driven
      by innovation and cutting-edge developments at every step involved in the process
      of crystallization. Here, we present a step-by-step description of various steps
      involved in GPCR crystallization starting from recombinant expression to
      obtaining diffracting crystals. We also discuss the next frontiers in GPCR
      biology that are likely to be a primary focus for crystallography efforts in the
      next decade or so. 

PMID- 25857801
TI  - Introduction. Preface.

PMID- 25857800
TI  - Structure-based biophysical analysis of the interaction of rhodopsin with G
      protein and arrestin.
AB  - In this chapter, we describe a set of complementary techniques that we use to
      study the activation of rhodopsin, a G protein-coupled receptor (GPCR), and its
      functional interactions with G protein and arrestin. The protein reagents used
      for these studies come from native disc membranes or heterologous expression, and
      G protein and arrestin are often replaced with less complex synthetic peptides
      derived from key interaction sites of these binding partners (BPs). We first
      report on our approach to protein X-ray crystallography and describe how protein
      crystals from native membranes are obtained. The crystal structures provide
      invaluable resolution, but other techniques are required to assess the dynamic
      equilibria characteristic for active GPCRs. The simplest approach is "Extra Meta
      II," which uses UV/Vis absorption spectroscopy to monitor the equilibrium of
      photoactivated states. Site-specific information about the BPs (e.g., arrestin)
      is added by fluorescence techniques employing mutants labeled with reporter
      groups. All functional changes in both the receptor and interacting proteins or
      peptides are seen with highest precision using Fourier transform infrared (FTIR)
      difference spectroscopy. In our approach, the lack of site-specific information
      in FTIR is overcome by parallel molecular dynamics simulations, which are
      employed to interpret the results and to extend the timescale down to the range
      of conformational substates. 

PMID- 25857802
TI  - Targeted deletion of Vglut2 expression in the embryonal telencephalon promotes an
      anxiolytic phenotype of the adult mouse.
AB  - BACKGROUND: Anxiety is a natural emotion experienced by all individuals. However,
      when anxiety becomes excessive, it contributes to the substantial group of
      anxiety disorders that affect one in three people and thus are among the most
      common psychiatric disorders. Anxiolysis, the reduction of anxiety, is mediated
      via several large groups of therapeutical compounds, but the relief is often only
      temporary, and increased knowledge of the neurobiology underlying anxiety is
      needed in order to improve future therapies. AIM: We previously demonstrated that
      mice lacking forebrain expression of the Vesicular glutamate transporter 2
      (Vglut2) from adolescence showed a strong anxiolytic behaviour as adults. In the
      current study, we wished to analyse if removal of Vglut2 expression already from
      mid-gestation of the mouse embryo would give rise to similar anxiolysis in the
      adult mouse. METHODS: We produced transgenic mice lacking Vglut2 from mid
      gestation and analysed their affective behaviour, including anxiety, when they
      had reached adulthood. RESULTS: The transgenic mice lacking Vglut2 expression
      from mid-gestation showed certain signs of anxiolytic behaviour, but this
      phenotype was not as prominent as when Vglut2 was removed during adolescence.
      CONCLUSION: Our results suggest that both embryonal and adolescent forebrain
      expression of Vglut2 normally contributes to balancing the level of anxiety. As
      the neurobiological basis for anxiety is similar across species, our results in
      mice may help improve the current understanding of the neurocircuitry of anxiety,
      and hence anxiolysis, also in humans.

PMID- 25857803
TI  - The family 6 Carbohydrate Binding Module (CtCBM6) of glucuronoxylanase
      (CtXynGH30) of Clostridium thermocellum binds decorated and undecorated xylans
      through cleft A.
AB  - CtCBM6 of glucuronoxylan-xylanohydrolase (CtXynGH30) from Clostridium
      thermocellum was cloned, expressed and purified as a soluble ~14 kDa protein.
      Quantitative binding analysis with soluble polysaccharides by affinity
      electrophoresis and ITC revealed that CtCBM6 displays similar affinity towards
      decorated and undecorated xylans by binding wheat- and rye-arabinoxylans,
      beechwood-, birchwood- and oatspelt-xylan. Protein melting studies confirmed
      thermostable nature of CtCBM6 and that Ca(2+) ions did not affect its structure
      stability and binding affinity significantly. The CtCBM6 structure was modeled
      and refined and CD spectrum displayed 44% beta-strands supporting the predicted
      structure. CtCBM6 displays a jelly roll beta-sandwich fold presenting two
      potential carbohydrate binding clefts, A and B. The cleft A, is located between
      two loops connecting beta4-beta5 and beta8-beta9 strands. Tyr28 and Phe84 present
      on these loops make a planar hydrophobic binding surface to accommodate sugar
      ring of ligand. The cleft B, is located on concave surface of beta-sandwich fold.
      Tyr34 and Tyr104 make a planar hydrophobic platform, which may be inaccessible to
      ligand due to hindrance by Pro68. Site-directed mutagenesis revealed Tyr28 and
      Phe84 in cleft A, playing a major role in ligand binding. The results suggest
      that CtCBM6 interacts with carbohydrates through cleft A, which recognizes
      equally well both decorated and un-decorated xylans.

PMID- 25857805
TI  - Pregnancies in tattooed female tattooists: an observational study.

PMID- 25857804
TI  - Going into surgery: Risk factors for hypertrophic scarring.
AB  - The aim of this study was to examine the association between possible risk
      factors for excessive scarring and the formation of hypertrophic scars (HTS).
      Hypertrophic skin scarring remains a difficult problem in medicine and can cause
      considerable morbidity. Nevertheless, few extensive prospective studies have been
      conducted which assess risk factors in relation to HTS formation. Therefore, a
      prospective observational study was performed. Patients who had elective
      cardiothoracic surgery were followed for the duration of 1 year and information
      was collected about a variety of possible risk factors in these patients. The
      associations between the risk factors and the development of HTSs were
      investigated. Body mass index, ethnic background, and scar related factors are
      positively associated with HTS formation. Antihypertensive therapeutics and
      factors influencing erythropoiesis are negatively associated with HTS formation. 

PMID- 25857806
TI  - Response to "autologous fat grafting: in search of the optimal technique".

PMID- 25857807
TI  - Use of a Fibrinogen/Thrombin-Based Collagen Fleece (TachoComb, TachoSil) With a
      Stapled Closure to Prevent Pancreatic Fistula Formation Following Distal
      Pancreatectomy.
AB  - BACKGROUND/PURPOSE: Postoperative pancreatic fistula formation remains a source
      of significant morbidity following distal pancreatectomy. The aim of this study
      was to evaluate the rate of clinically significant fistulas (International Study
      Group on Pancreatic Fistula grade B and grade C) after distal pancreatectomy
      using a fibrinogen/thrombin-based collagen fleece (TachoComb, TachoSil) with a
      stapled closure. METHODS: Seventy-five patients underwent distal pancreatectomy
      at our institution between January 2005 and March 2014. A fibrinogen/thrombin
      based collagen fleece was applied to the staple line of the pancreas before
      stapling. RESULTS: Twenty-six patients (34.7%) developed a pancreatic fistula, 8
      patients (10.7%) developed a grade B fistula, and no patients developed a grade C
      fistula. The duration of the drain was significantly different in patients with
      or without a pancreatic fistula (8.0 +/- 4.5 vs. 5.4 +/- 1.3 days, P = .0003).
      Histological analysis showed that there was a tight covering with the
      fibrinogen/thrombin-based collagen fleece. CONCLUSION: The fibrinogen/thrombin
      based collagen fleece (TachoComb, TachoSil) with a stapled closure has low rates
      of fistula formation and provides a safe alternative to the conventional stapled
      technique in distal pancreatectomy.

PMID- 25857808
TI  - Salvia miltiorrhiza: A source for anti-Alzheimer's disease drugs.
AB  - CONTEXT: Alzheimer's disease (AD) is a devastating neurodegenerative disorder
      that affects millions of elderly people worldwide. However, no efficient
      therapeutic method for AD has yet been developed. Recently, Salvia miltiorrhiza
      Bunge (Lamiaceae), a well-known traditional Chinese medicine which is widely used
      for treating cardio-cerebrovascular, exerts multiple neuroprotective effects and
      is attracting increased attention for the treatment of AD. OBJECTIVE: The
      objective of this study is to discuss the neuroprotective effects and
      neurogenesis-inducing activities of S. miltiorrhiza components. METHODS: A
      detailed search using major electronic search engines (such as Pubmed,
      ScienceDirect, and Google Scholar) was undertaken with the search terms: Salvia
      miltiorrhiza, the components of S. miltiorrhiza such as salvianolic acid B,
      salvianolic acid A, danshensu, tanshinone I, tanshinone IIA, cryptotanshinone,
      dihydrotanshinone, and neuroprotection. RESULTS: Salvia miltiorrhiza components
      exert multiple neuroprotective potentials relevant to AD, such as anti-amyloid
      beta, antioxidant, anti-apoptosis, acetylcholinesterase inhibition, and anti
      inflammation. Moreover, S. miltiorrhiza promotes neurogenesis of neural
      progenitor cells/stem cells in vitro and in vivo. CONCLUSIONS: The properties of
      S. miltiorrhiza indicate their therapeutic potential in AD via multiple
      mechanisms. In addition, S. miltiorrhiza provides lead compounds for developing
      new drugs against AD.

PMID- 25857809
TI  - Understanding racial and sex-related variations in AF treatment: "Difference,"
      "disparity," or "bias"?

PMID- 25857811
TI  - Stem cells: SIRT7, the UPR and HSC ageing.

PMID- 25857810
TI  - Multidimensional proteomics for cell biology.
AB  - The proteome is a dynamic system in which each protein has interconnected
      properties - dimensions - that together contribute to the phenotype of a cell.
      Measuring these properties has proved challenging owing to their diversity and
      dynamic nature. Advances in mass spectrometry-based proteomics now enable the
      measurement of multiple properties for thousands of proteins, including their
      abundance, isoform expression, turnover rate, subcellular localization, post
      translational modifications and interactions. Complementing these experimental
      developments are new data analysis, integration and visualization tools as well
      as data-sharing resources. Together, these advances in the multidimensional
      analysis of the proteome are transforming our understanding of various cellular
      and physiological processes. 

PMID- 25857813
TI  - Rigid endoscopy in the out-patient clinic.
AB  - OBJECTIVE: This paper presents an efficient and ergonomic system for performing
      rigid endoscopic examination in the out-patient clinic setting. The set-up
      encourages user comfort, and facilitates clear images of the nasal mucosa, nasal
      cavity and paranasal sinuses. EQUIPMENT: This consisted of anti-fog solution, a 5
      ml syringe, a cardboard receiver and gauze. CONCLUSION: By using disposable
      equipment we encourage good infection control practices. We recommend that users
      of rigid endoscopes in the out-patient setting consider setting up for each
      patient in this manner.

PMID- 25857814
TI  - Monod's conception of chance: its diversity and relevance today.
AB  - In his famous book Le hasard et la necessite (1970), Monod claims that natural
      evolution is based on the interplay between chance and necessity bringing about
      adaptive evolutionary change. This article addresses a set of related questions
      about Monod's conception of chance: what does he mean when he uses the term
      "chance"? Does he invoke one or many different concepts of chance? What are the
      implications of his conception about the issue of the deterministic or
      indeterministic nature of the biological world? Is Monod's view of what chance is
      relevant in contemporary biology? This paper, structured by these four questions,
      aims at providing a synthetic study of the way Monod conceptualizes chance,
      particularly highlighting the metaphysical and epistemological implications of
      his conception and its value in biology today. 

PMID- 25857812
TI  - Building endocytic pits without clathrin.
AB  - How endocytic pits are built in clathrin- and caveolin-independent endocytosis
      still remains poorly understood. Recent insight suggests that different forms of
      clathrin-independent endocytosis might involve the actin-driven focusing of
      membrane constituents, the lectin-glycosphingolipid-dependent construction of
      endocytic nanoenvironments, and Bin-Amphiphysin-Rvs (BAR) domain proteins serving
      as scaffolding modules. We discuss the need for different types of
      internalization processes in the context of diverse cellular functions, the
      existence of clathrin-independent mechanisms of cargo recruitment and membrane
      bending from a biological and physical perspective, and finally propose a generic
      scheme for the formation of clathrin-independent endocytic pits.

PMID- 25857815
TI  - Monod as the founder of a new discipline: local and international contexts.
AB  - Monod gained stature as an experimentalist and theorist as well as a discipline
      builder. The essay reviews the intimate connection of the intellectual and
      institutional projects in his career. A brief comparison with the development of
      the new science of molecular biology across the English Channel highlights the
      commonalities and specificities of the disciplinary projects in France and
      Britain and the role that individuals like Monod played in their formation. The
      article argues that there was not a single path that led to the rise of molecular
      biology. Rather individual initiatives and historical contingencies very much
      shaped local outcomes. 

PMID- 25857816
TI  - Science and the applications of science from Louis Pasteur to Jacques Monod.
AB  - Jacques Monod's ideas on the applications of science came within the scope of a
      long tradition at the Institut Pasteur. Louis Pasteur, whose scientific career
      was characterized by a permanent come and go between science and its
      applications, long opposed the idea of getting any income from his research,
      until the financial needs of the Institut Pasteur made him change his mind. As
      for Jacques Monod, he remained a fervent supporter of basic science during his
      whole scientific career. However, once he became director of the Institut
      Pasteur, he realized that the applications of research had to be developed to
      support the institute from a financial point of view. Thus, he reorganized the
      valorization of research in the institute, through an incitation of scientists to
      develop projects with possible applications, and by creating a company, Institut
      Pasteur Production, for which he had a factory built, and which was in charge of
      producing and commercializing the vaccines and reagents stemming from the
      research at the Institut Pasteur. 

PMID- 25857819
TI  - Rational material design for ultrafast rechargeable lithium-ion batteries.
AB  - Rechargeable lithium-ion batteries (LIBs) are important electrochemical energy
      storage devices for consumer electronics and emerging electrical/hybrid vehicles.
      However, one of the formidable challenges is to develop ultrafast charging LIBs
      with the rate capability at least one order of magnitude (>10 C) higher than that
      of the currently commercialized LIBs. This tutorial review presents the state-of
      the-art developments in ultrafast charging LIBs by the rational design of
      materials. First of all, fundamental electrochemistry and related
      ionic/electronic conduction theories identify that the rate capability of LIBs is
      kinetically limited by the sluggish solid-state diffusion process in electrode
      materials. Then, several aspects of the intrinsic materials, materials
      engineering and processing, and electrode materials architecture design towards
      maximizing both ionic and electronic conductivity in the electrode with a short
      diffusion length are deliberated. Finally, the future trends and perspectives for
      the ultrafast rechargeable LIBs are discussed. Continuous rapid progress in this
      area is essential and urgent to endow LIBs with ultrafast charging capability to
      meet huge demands in the near future. 

PMID- 25857818
TI  - [Non-VKA oral anticoagulants: an update for the clinical biologists].
AB  - Non-VKA oral anticoagulants (NOACs), thanks to their ease of use and their
      similar or superior safety/efficacy profiles versus warfarin, have now widely
      reached the lucrative market of anticoagulation. However, while the marketing
      authorization holders always claim, in a quite unclear way that no monitoring is
      required, accumulative evidence and cases of major bleeding have been described
      in the literature and reported by spontaneous reporting systems at the
      regulator's level. These compounds are usually given at fixed doses without
      routine coagulation monitoring. However, new data suggests that an assessment of
      the response at the individual level could improve the benefit-risk ratio of, at
      least dabigatran. Therefore, in certain patient populations, i.e. acute or
      chronic renal impairment or multiple drug interactions, measurement of drug
      exposure may be useful to ensure an optimal treatment response. More specific
      circumstances such as patients experiencing a haemorrhagic or thromboembolic
      event during the treatment duration, patients who require urgent surgery or an
      invasive procedure, or patient with a suspected overdose could benefit from such
      a measurement. This article aims at providing guidance on how to best estimate
      the intensity of anticoagulation using laboratory assays in daily practice. 

PMID- 25857817
TI  - Mutational status of naevus-associated melanomas.
AB  - BACKGROUND: The origin of melanoma has always been a debated subject, as well as
      the role of adjacent melanocytic naevi. Epidemiological and histopathological
      studies point to melanomas arising either de novo or from a naevus. OBJECTIVES:
      To evaluate the presence of mutations in genes from well-known melanomagenesis
      pathways in a large series of naevus-associated melanomas. MATERIALS AND METHODS:
      Sixty-one melanomas found in association with a pre-existing naevus were
      microdissected, after careful selection of cell subpopulations, and submitted to
      Sanger sequencing of the BRAF, NRAS, c-KIT, PPP6C, STK19 and RAC1 genes. Each
      gene was evaluated twice in all samples by sequencing or by sequencing and
      another confirmation method, allele-specific fluorescent polymerase chain
      reaction (PCR) and capillary electrophoresis detection or by SNaPshot analysis.
      Only mutations confirmed via two different molecular methods or twice by
      sequencing were considered positive. RESULTS: The majority of cases presented
      concordance of mutational status between melanoma and the associated naevus for
      all six genes (40 of 60; 66.7%). Nine cases presented concomitant BRAF and NRAS
      mutations, including one case in which both the melanoma and the adjacent naevus
      harboured V600E and Q61K double mutations. In two cases, both melanoma and
      associated naevus located on acral sites were BRAF mutated, including an acral
      lentiginous melanoma. CONCLUSIONS: To our knowledge this is the largest naevus
      associated melanoma series evaluated molecularly. The majority of melanomas and
      adjacent naevi in our sample share the same mutational profile, corroborating the
      theory that the adjacent naevus and melanoma are clonally related and that the
      melanoma originated within a naevus.

PMID- 25857820
TI  - Advances in Toll-like receptor biology: Modes of activation by diverse stimuli.
AB  - As we learn more about the biology of the Toll-like receptors (TLRs), a wide
      range of molecules that can activate this fascinating family of pattern
      recognition receptors emerges. In addition to conserved pathogenic components,
      endogenous danger signals created upon tissue damage are also sensed by TLRs.
      Detection of these types of stimuli results in TLR mediated inflammation that is
      vital to fight pathogenic invasion and drive tissue repair. Aberrant activation
      of TLRs by pathogenic and endogenous ligands has also been linked with the
      pathogenesis of an increasing number of infectious and autoimmune diseases,
      respectively. Most recently, allergen activation of TLRs has also been described,
      creating a third broad class of TLR stimulus that has helped to shed light on the
      pathogenesis of allergic disease. To date, microbial activation of TLRs remains
      best characterized. Each member of the TLR family senses a specific subset of
      pathogenic ligands, pathogen associated molecular patterns (PAMPS), and a wealth
      of structural and biochemical data continues to reveal the molecular mechanisms
      of TLR activation by PAMPs, and to demonstrate how receptor specificity is
      achieved. In contrast, the mechanisms by which endogenous molecules and allergens
      activate TLRs remain much more mysterious. Here, we provide an overview of our
      current knowledge of how very diverse stimuli activate the same TLRs and the
      structural basis of these modes of immunity. 

PMID- 25857821
TI  - Monoamine Oxidase A is Required for Rapid Dendritic Remodeling in Response to
      Stress.
AB  - BACKGROUND: Acute stress triggers transient alterations in the synaptic release
      and metabolism of brain monoamine neurotransmitters. These rapid changes are
      essential to activate neuroplastic processes aimed at the appraisal of the
      stressor and enactment of commensurate defensive behaviors. Threat evaluation has
      been recently associated with the dendritic morphology of pyramidal cells in the
      orbitofrontal cortex (OFC) and basolateral amygdala (BLA); thus, we examined the
      rapid effects of restraint stress on anxiety-like behavior and dendritic
      morphology in the BLA and OFC of mice. Furthermore, we tested whether these
      processes may be affected by deficiency of monoamine oxidase A (MAO-A), the
      primary enzyme catalyzing monoamine metabolism. METHODS: Following a short-term
      (1-4h) restraint schedule, MAO-A knockout (KO) and wild-type (WT) mice were
      sacrificed, and histological analyses of dendrites in pyramidal neurons of the
      BLA and OFC of the animals were performed. Anxiety-like behaviors were examined
      in a separate cohort of animals subjected to the same experimental conditions.
      RESULTS: In WT mice, short-term restraint stress significantly enhanced anxiety
      like responses, as well as a time-dependent proliferation of apical (but not
      basilar) dendrites of the OFC neurons; conversely, a retraction in BLA dendrites
      was observed. None of these behavioral and morphological changes were observed in
      MAO-A KO mice. CONCLUSIONS: These findings suggest that acute stress induces
      anxiety-like responses by affecting rapid dendritic remodeling in the pyramidal
      cells of OFC and BLA; furthermore, our data show that MAO-A and monoamine
      metabolism are required for these phenomena.

PMID- 25857823
TI  - The regulatory effects of Cissus quadrangularis on some enzymes involved in
      carbohydrate metabolism in streptozotocin-induced diabetic rats.
AB  - CONTEXT: Diabetes mellitus (DM) is probably the single most important metabolic
      disease and is widely recognized as one of the leading causes of death and
      disability. Cissus quadrangularis Linn. (Vitaceae) is a medicinal food and is
      reported to possess hypoglycemic activity. OBJECTIVE: The present study evaluates
      the effect of ethyl acetate fraction of C. quadrangularis stem (CQSF) on
      carbohydrate metabolism in hepatic tissues of experimental diabetic rats. The
      phytochemical compounds present in the CQSF extract were identified by gas
      chromatography-mass spectrometry (GC-MS) analysis. MATERIALS AND METHODS:
      Diabetic animals were treated with CQSF (50, 100, and 200 mg/kg body weight) for
      45 d. Several indices such as blood glucose, glycated hemoglobin (HbA1c),
      insulin, liver function tests, hepatic glycogen content, and the activities of
      carbohydrate-metabolizing enzymes were assayed after 45 d of extract treatment.
      RESULTS: A pronounced effect was observed with extract doses 100 and 200 mg/kg
      body weight. CQSF at a dose of 100 mg/kg body weight significantly decreased the
      altered levels of blood glucose by about 56%. CQSF also modulated the activities
      of carbohydrate-metabolizing enzymes by significantly increasing the activity of
      hexokinase (1.9-fold) and pyruvate kinase (2.2-fold) and significantly reducing
      the activity of glucose-6-phosphatase (41.23%), fructose-1,6-diphosphatase
      (29.43%), and glycogen phosphorylase (35.07%). GC-MS analysis revealed the
      presence of 10 chemical constituents, and N-methyl-1-adamantane acetamide was
      found to be the prevailing compound in the extract. DISCUSSION AND CONCLUSION:
      The current study suggests the antidiabetic potential of CQSF, mediated through
      the regulation of carbohydrate metabolic enzyme activities.

PMID- 25857822
TI  - Dopamine Regulates Approach-Avoidance in Human Sensation-Seeking.
AB  - BACKGROUND: Sensation-seeking is a trait that constitutes an important
      vulnerability factor for a variety of psychopathologies with high social cost.
      However, little is understood either about the mechanisms underlying motivation
      for intense sensory experiences or their neuropharmacological modulation in
      humans. METHODS: Here, we first evaluate a novel paradigm to investigate
      sensation-seeking in humans. This test probes the extent to which participants
      choose either to avoid or self-administer an intense tactile stimulus (mild
      electric stimulation) orthogonal to performance on a simple economic decision
      making task. Next we investigate in a different set of participants whether this
      behavior is sensitive to manipulation of dopamine D2 receptors using a within
      subjects, placebo-controlled, double-blind design. RESULTS: In both samples,
      individuals with higher self-reported sensation-seeking chose a greater
      proportion of mild electric stimulation-associated stimuli, even when this
      involved sacrifice of monetary gain. Computational modelling analysis determined
      that people who assigned an additional positive economic value to mild electric
      stimulation-associated stimuli exhibited speeding of responses when choosing
      these stimuli. In contrast, those who assigned a negative value exhibited slowed
      responses. These findings are consistent with involvement of low-level, approach
      avoidance processes. Furthermore, the D2 antagonist haloperidol selectively
      decreased the additional economic value assigned to mild electric stimulation
      associated stimuli in individuals who showed approach reactions to these stimuli
      under normal conditions (behavioral high-sensation seekers). CONCLUSIONS: These
      findings provide the first direct evidence of sensation-seeking behavior being
      driven by an approach-avoidance-like mechanism, modulated by dopamine, in humans.
      They provide a framework for investigation of psychopathologies for which extreme
      sensation-seeking constitutes a vulnerability factor.

PMID- 25857824
TI  - Morphologically low-grade spiradenocarcinoma: a clinicopathologic study of 19
      cases with emphasis on outcome and MYB expression.
AB  - Spiradenocarcinoma is a rare skin adnexal neoplasm with potential for aggressive
      behavior, classified histologically into low- and high-grade tumors.
      Morphologically, low-grade tumors are thought to behave more favorably. Limited
      information is available, however, with only 18 published cases. To study their
      clinical behavior, histological features, and the diagnostic value of
      immunohistochemistry, 19 morphologically low-grade spiradenocarcinomas were
      retrieved and compared with 21 spiradenomas and cylindromas. H&E-stained sections
      were reviewed, follow-up was obtained, and immunohistochemistry for Ki-67, p53
      and, MYB was performed. The tumors were solitary, measuring 0.8-7 cm (median: 2.7
      cm), with a predilection for the head and neck of elderly patients (median age:
      72 years; range 53-92) without gender bias. Histologically, the tumors were
      multinodular and located in deep dermis and subcutis. A pre-existing spiradenoma
      was present in all cases. The malignant component was characterized by expansile
      growth with loss of the dual cell population, up to moderate cytological atypia
      and increased mitotic activity (median: 10/10 HPF; range 1-28). Additional
      findings included squamoid differentiation (n=9), necrosis (n=7), and ulceration
      (n=5). P53 expression was variable and no significant differences were noted in
      the benign compared with the malignant parts of the tumors. In contrast, in the
      malignant components the Ki-67 proliferative index was slightly increased, and
      MYB expression was lost. Follow-up (median: 67 months; range: 13-132) available
      for 16 patients (84%) revealed a local recurrence rate of 19% but no metastases
      or disease-related mortality. In this large study with long-term follow-up, we
      demonstrate that spiradenocarcinomas with low-grade morphology pursue an indolent
      course, characterized by local recurrence only. Metastases and disease-related
      mortality appear to be exceptional. Lack of MYB expression may be useful as an
      additional aid in the diagnosis of these challenging tumors.

PMID- 25857825
TI  - ALK rearrangement and overexpression in epithelioid fibrous histiocytoma.
AB  - Epithelioid benign fibrous histiocytoma, also known as 'epithelioid cell
      histiocytoma,' has traditionally been considered a morphologic variant of
      cutaneous fibrous histiocytoma (dermatofibroma). In addition to its
      characteristic epithelioid cytomorphology, several phenotypic differences suggest
      that epithelioid fibrous histiocytoma may differ biologically from other
      variants. Recently, ALK rearrangement was described in two cases of epithelioid
      fibrous histiocytoma and separately in two cases reported as 'atypical' fibrous
      histiocytoma (with epithelioid features), with corresponding ALK expression
      detectable by immunohistochemistry. The goals of this study were to determine the
      frequency of ALK expression by immunohistochemistry in epithelioid fibrous
      histiocytoma, to determine its value for the diagnosis of epithelioid fibrous
      histiocytoma among variants and other histologic mimics, and to evaluate ALK gene
      rearrangement in epithelioid fibrous histiocytoma. ALK protein expression was
      evaluated in whole tissue sections from 33 epithelioid fibrous histiocytomas, 41
      other cases of fibrous histiocytoma (11 conventional and 10 each cellular,
      atypical, and aneurysmal types), 10 cutaneous syncytial myoepitheliomas, and 5
      atypical fibroxanthomas, using a mouse anti-ALK monoclonal antibody. Fluorescence
      in situ hybridization (FISH) was performed using break-apart probes. In total,
      29/33 (88%) cases of epithelioid fibrous histiocytoma showed diffuse cytoplasmic
      ALK expression. Staining was moderate to strong in intensity in all cases except
      one, which showed diffuse weak expression. All other tumor types were negative
      for ALK expression. FISH demonstrated ALK rearrangement in all ALK-immunoreactive
      cases evaluated (n=13), and not in one ALK expression-negative epithelioid
      fibrous histiocytoma successfully examined. In conclusion, the majority of
      epithelioid fibrous histiocytomas demonstrate ALK expression and ALK gene
      rearrangement. ALK expression is not seen in other variants of fibrous
      histiocytoma, providing a useful diagnostic tool to distinguish epithelioid
      fibrous histiocytoma from most histologic mimics. The expression of ALK suggests
      that epithelioid fibrous histiocytoma is a biologically distinct tumor type,
      unrelated to conventional fibrous histiocytoma and histologic variants. 

PMID- 25857827
TI  - Gray-Level Co-Occurrence Matrix Texture Analysis of Breast Tumor Images in
      Prognosis of Distant Metastasis Risk.
AB  - Owing to exceptional heterogeneity in the outcome of invasive breast cancer it is
      essential to develop highly accurate prognostic tools for effective therapeutic
      management. Based on this pressing need, we aimed to improve breast cancer
      prognosis by exploring the prognostic value of tumor histology image analysis.
      Patient group (n=78) selection was based on invasive breast cancer diagnosis
      without systemic treatment with a median follow-up of 147 months. Gray-level co
      occurrence matrix texture analysis was performed retrospectively on primary tumor
      tissue section digital images stained either nonspecifically with hematoxylin and
      eosin or specifically with a pan-cytokeratin antibody cocktail for epithelial
      malignant cells. Univariate analysis revealed stronger association with
      metastasis risk by texture analysis when compared with clinicopathological
      parameters. The combination of individual clinicopathological and texture
      variables into composite scores resulted in further powerful enhancement of
      prognostic performance, with an accuracy of up to 90%, discrimination efficiency
      by the area under the curve [95% confidence interval (CI)] of 0.94 (0.87-0.99)
      and hazard ratio (95% CI) of 20.1 (7.5-109.4). Internal validation was
      successfully performed by bootstrap and split-sample cross-validation, suggesting
      that the models are generalizable. Whereas further validation is needed on an
      external set of patients, this preliminary study indicates the potential use of
      primary breast tumor histology texture as a highly accurate, simple, and cost
      effective prognostic indicator of distant metastasis risk. 

PMID- 25857828
TI  - Adaptive seating systems in children with severe cerebral palsy across
      International Classification of Functioning, Disability and Health for Children
      and Youth version domains: a systematic review.
AB  - AIM: The aim of this study was to systematically review the effect of adaptive
      seating systems (AdSSs) in young people less than 19 years of age with severe
      cerebral palsy (CP), with particular focus on child-related outcomes across all
      components of the functioning and disability domains of the International
      Classification of Functioning, Disability, and Health for Children and Youth
      version (ICF-CY). METHOD: Literature searches of studies published from 1975 to
      October 2014 were performed. Methodological quality and the risk of bias were
      analysed using Sackett's level of evidence, the American Academy for Cerebral
      Palsy and Developmental Medicine guidelines, and Mallen criteria for
      observational studies. RESULTS: Nine studies fulfilled the selection criteria.
      All studies had level IV evidence and were of moderate methodological quality.
      The results focused on the effects of AdSSs on postural control and on upper
      extremity function and on additional child-related outcomes. The results
      suggested that AdSSs that include trunk and hip support devices may improve
      postural control outcomes, and that special-purpose AdSSs may improve self-care
      and play behaviour at home. INTERPRETATION: Because of a low level of evidence
      and the moderate methodological quality of the studies available, no robust
      conclusions can be drawn. Nevertheless, the data suggest that AdSSs may be able
      to improve activity and participation at home among children with severe CP. More
      studies of high methodological quality addressing the effect of AdSSs on activity
      and participation are urgently needed. Suggestions for future research are
      provided.

PMID- 25857826
TI  - Safe prescribing of non-steroidal anti-inflammatory drugs in patients with
      osteoarthritis--an expert consensus addressing benefits as well as
      gastrointestinal and cardiovascular risks.
AB  - BACKGROUND: There are several guidelines addressing the issues around the use of
      NSAIDs. However, none has specifically addressed the upper versus lower
      gastrointestinal (GI) risk of COX-2 selective and non-selective compounds nor the
      interaction at both the GI and cardiovascular (CV) level of either class of drugs
      with low-dose aspirin. This Consensus paper aims to develop statements and
      guidance devoted to these specific issues through a review of current evidence by
      a multidisciplinary group of experts. METHODS: A modified Delphi consensus
      process was adopted to determine the level of agreement with each statement and
      to determine the level of agreement with the strength of evidence to be assigned
      to the statement. RESULTS: For patients with both low GI and CV risks, any non
      selective NSAID (ns-NSAID) alone may be acceptable. For those with low GI and
      high CV risk, naproxen may be preferred because of its potential lower CV risk
      compared with other ns-NSAIDs or COX-2 selective inhibitors, but celecoxib at the
      lowest approved dose (200 mg once daily) may be acceptable. In patients with high
      GI risk, if CV risk is low, a COX-2 selective inhibitor alone or ns-NSAID with a
      proton pump inhibitor appears to offer similar protection from upper GI events.
      However, only celecoxib will reduce mucosal harm throughout the entire GI tract.
      When both GI and CV risks are high, the optimal strategy is to avoid NSAID
      therapy, if at all possible. CONCLUSIONS: Time is now ripe for offering patients
      with osteoarthritis the safest and most cost-effective therapeutic option, thus
      preventing serious adverse events which could have important quality of life and
      resource use implications. Please see related article:
      http://dx.doi.org/10.1186/s12916-015-0291-x.

PMID- 25857829
TI  - Contamination of the Hospital Environment From Potential Clostridium difficile
      Excretors Without Active Infection.
AB  - Clostridium difficile was recovered from 33 (34%) of 98 rooms of patients who
      were excretors compared with 36 (49%) of 73 rooms of patients with active
      infection. Not all laboratory algorithms can distinguish between these 2 groups,
      yet both may be a significant source for ongoing transmission.

PMID- 25857830
TI  - Palmitate exerts opposite effects on proliferation and differentiation of
      skeletal myoblasts.
AB  - The purpose of the study was to examine mechanisms controlling cell cycle
      progression/arrest and differentiation of mouse C2C12 myoblasts exposed to long
      chain saturated fatty acid salt, palmitate. Treatment of proliferating myoblasts
      with palmitate (0.1 mmol/l) markedly decreased myoblast number. Cyclin A and
      cyclin D1 levels decreased, whereas total p21 and p21 complexed with cyclin
      dependent kinase-4 (cdk4) increased in myoblasts treated with palmitate. In cells
      induced to differentiation addition of palmitate augmented the level of cyclin
      D3, the early (myogenin) and late (alpha-actinin, myosin heavy chain) markers of
      myogenesis, and caused an increase of myotube diameter. In conclusion, exposure
      to palmitate inhibits proliferation of myoblasts through a decrease in cyclin A
      and cyclin D1 levels and an increase of p21-cdk4 complex formation; however, it
      promotes cell cycle exit, myogenic differentiation and myotube growth. 

PMID- 25857836
TI  - Mobilization of endogenous bone marrow-derived stem cells in a thioacetamide
      induced mouse model of liver fibrosis.
AB  - The clinical significance of enhancing endogenous circulating haematopoietic stem
      cells is becoming increasingly recognized, and the augmentation of circulating
      stem cells using granulocyte-colony stimulating factor (G-CSF) has led to
      promising preclinical and clinical results for several liver fibrotic conditions.
      However, this approach is largely limited by cost and the infeasibility of
      maintaining long-term administration. Preclinical studies have reported that
      StemEnhance, a mild haematopoietic stem cell mobilizer, promotes cardiac muscle
      regeneration and remedies the manifestation of diabetes. However, the
      effectiveness of StemEnhance in ameliorating liver cirrhosis has not been
      studied. This study is the first to evaluate the beneficial effect of StemEnhance
      administration in a thioacetamide-induced mouse model of liver fibrosis.
      StemEnhance augmented the number of peripheral CD34-positive cells, reduced
      hepatic fibrosis, improved histopathological changes, and induced endogenous
      liver proliferation. In addition, VEGF expression was up-regulated, while TNF
      alpha expression was down-regulated in thioacetamide-induced fibrotic livers
      after StemEnhance intake. These data suggest that StemEnhance may be useful as a
      potential therapeutic candidate for liver fibrosis by inducing reparative effects
      via mobilization of haematopoietic stem cells. 

PMID- 25857831
TI  - Effects of nicotine on ethanol-induced locomotor sensitization: A model of
      neuroadaptation.
AB  - Co-morbid use of nicotine-containing tobacco products and alcohol (ethanol) is
      prevalent in young adults initiating use and in alcohol dependent adults,
      suggesting that these drugs in combination may increase risk to develop
      dependence on one or both drugs. Neuroadaptations caused by repeated drug
      exposure are related to the development of drug dependence and vulnerability to
      relapse. Locomotor sensitization has been used as a behavioral measure used to
      detect changes in neural drug sensitivity that are thought to contribute to drug
      dependence and relapse. Locomotor sensitization was measured in the current
      studies to examine potential differences in the effects of nicotine and ethanol
      given alone and in combination. Baseline activity levels of DBA/2J mice were
      assessed on 2 days, then mice were treated for 10 days with saline, nicotine (1
      or 2mg/kg of nicotine tartrate), ethanol (1 or 2g/kg), or nicotine plus ethanol
      and locomotor activity was assessed every third day. On the following day, all
      mice were challenged with ethanol to measure the expression of sensitization.
      Mice treated with both nicotine and ethanol exhibited greater stimulation than
      predicted from the combined independent effects of these drugs, consistent with
      our previously published results. The combined effects of nicotine and ethanol on
      locomotor sensitization were dependent on the dose of ethanol and whether testing
      was performed after the drugs were given together, or after challenge with
      ethanol alone. These results suggest that nicotine and ethanol in combination can
      have neuroadaptive effects that differ from the independent effects of these
      drugs. 

PMID- 25857838
TI  - Design attributes of long-circulating polymeric drug delivery vehicles.
AB  - Following systemic administration polymeric drug delivery vehicles allow for a
      controlled and targeted release of the encapsulated medication at the desired
      site of action. For an elevated and organ specific accumulation of their cargo,
      nanocarriers need to avoid opsonization, activation of the complement system and
      uptake by macrophages of the mononuclear phagocyte system. In this respect,
      camouflaged vehicles revealed a delayed elimination from systemic circulation and
      an improved target organ deposition. For instance, a steric shielding of the
      carrier surface by poly(ethylene glycol) substantially decreased interactions
      with the biological environment. However, recent studies disclosed possible
      deficits of this approach, where most notably, poly(ethylene glycol)-modified
      drug delivery vehicles caused significant immune responses. At present,
      identification of novel potential carrier coating strategies facilitating
      negligible immune reactions is an emerging field of interest in drug delivery
      research. Moreover, physical carrier properties including geometry and elasticity
      seem to be very promising design attributes to surpass numerous biological
      barriers, in order to improve the efficacy of the delivered medication. 

PMID- 25857837
TI  - A custom tailored model to investigate skin penetration in porcine skin and its
      comparison with human skin.
AB  - Reliable models for the determination of skin penetration and permeation are
      important for the development of new drugs and formulations. The intention of our
      study was to develop a skin penetration model which (1) is viable and well
      supplied with nutrients during the period of the experiment (2) is mimicking
      human skin as far as possible, but still is independent from the problems of
      supply and heterogeneity, (3) can give information about the penetration into
      different compartments of the skin and (4) considers specific inter-individual
      differences in skin thickness. In addition, it should be quick and inexpensive
      (5) and without ethical implications (6). Using a chemically divers set of four
      topically approved active pharmaceutical ingredients (APIs), namely diclofenac,
      metronidazole, tazarotene, and terbinafine, we demonstrated that the model allows
      reliable determination of drug concentrations in different layers of the viable
      epidermis and dermis. For APIs susceptible for skin metabolism, the extent of
      metabolic transformation in epidermis and dermis can be monitored. Furthermore, a
      high degree of accordance in the ability for discrimination of skin
      concentrations of the substances in different layers was found in models derived
      from porcine and human skin. Viability, proliferation, differentiation and
      markers for skin barrier function were surveyed in the model. This model, which
      we call 'Hamburg model of skin penetration' is particularly suited to support a
      rational ranking and selection of dermatological formulations within drug
      development projects. 

PMID- 25857840
TI  - Meeting report of the 2014 joint international congress of the International
      Liver Transplantation Society, Liver Intensive Care Group of Europe, and European
      Liver and Intestinal Association.
AB  - The 2014 Annual Meeting of the International Liver Transplantation Society was
      held in London, England. This was the 20th meeting of the Society and was marked
      by a joint meeting including the European Liver and Intestinal Association as
      well as the Liver Intensive Care Group of Europe. The meeting included symposia,
      invited lectures, debates, oral presentations, and posters. The principal themes
      were living donation, expanding the deceased donor pool, machine preservation,
      and new oral therapies for hepatitis C virus. This report highlights the
      scientific discussions of this meeting.

PMID- 25857839
TI  - Chip-based human liver-intestine and liver-skin co-cultures--A first step toward
      systemic repeated dose substance testing in vitro.
AB  - Systemic repeated dose safety assessment and systemic efficacy evaluation of
      substances are currently carried out on laboratory animals and in humans due to
      the lack of predictive alternatives. Relevant international regulations, such as
      OECD and ICH guidelines, demand long-term testing and oral, dermal, inhalation,
      and systemic exposure routes for such evaluations. So-called "human-on-a-chip"
      concepts are aiming to replace respective animals and humans in substance
      evaluation with miniaturized functional human organisms. The major technical
      hurdle toward success in this field is the life-like combination of human barrier
      organ models, such as intestine, lung or skin, with parenchymal organ
      equivalents, such as liver, at the smallest biologically acceptable scale. Here,
      we report on a reproducible homeostatic long-term co-culture of human liver
      equivalents with either a reconstructed human intestinal barrier model or a human
      skin biopsy applying a microphysiological system. We used a multi-organ chip
      (MOC) platform, which provides pulsatile fluid flow within physiological ranges
      at low media-to-tissue ratios. The MOC supports submerse cultivation of an intact
      intestinal barrier model and an air-liquid interface for the skin model during
      their co-culture with the liver equivalents respectively at (1)/100.000 the scale
      of their human counterparts in vivo. To increase the degree of organismal
      emulation, microfluidic channels of the liver-skin co-culture could be
      successfully covered with human endothelial cells, thus mimicking human
      vasculature, for the first time. Finally, exposure routes emulating oral and
      systemic administration in humans have been qualified by applying a repeated dose
      administration of a model substance - troglitazone - to the chip-based co
      cultures. 

PMID- 25857841
TI  - Using evidence on human milk and breastfeeding to transform care.

PMID- 25857842
TI  - A bivalent cationic dye enabling selective photo-inactivation against Gram
      negative bacteria.
AB  - A piperazine-modified Crystal Violet was found to be able to selectively
      inactivate Gram-negative bacteria upon visible light irradiation but left Gram
      positive bacteria less damaged, which can serve as a blueprint for the
      development of novel narrow-spectrum agents to replenish the current arsenal of
      photodynamic antimicrobial chemotherapy (PACT). 

PMID- 25857843
TI  - Evolutionary responses to climate change in parasitic systems.
AB  - Species may respond to climate change in many ecological and evolutionary ways.
      In this simulation study, we focus on the concurrent evolution of three traits in
      response to climate change, namely dispersal probability, temperature tolerance
      (or niche width), and temperature preference (optimal habitat). More
      specifically, we consider evolutionary responses in host species involved in
      different types of interaction, that is parasitism or commensalism, and for low
      or high costs of a temperature tolerance-fertility trade-off (cost of
      generalization). We find that host species potentially evolve all three traits
      simultaneously in response to increasing temperature but that the evolutionary
      response interacts and may be compensatory depending on the conditions. The
      evolutionary adjustment of temperature preference is slower in the parasitism
      than in commensalism scenario. Parasitism, in turn, selects for higher
      temperature tolerance and increased dispersal. High costs for temperature
      tolerance (i.e. generalization) restrict evolution of tolerance and thus lead to
      a faster response in temperature preference than that observed under low costs.
      These results emphasize the possible role of biotic interactions and the
      importance of 'multidimensional' evolutionary responses to climate change. 

PMID- 25857845
TI  - Correction for 'Multivariate multidistance tests for high-dimensional low sample
      size case-control studies'.

PMID- 25857844
TI  - Bacterial diversity of polluted surface sediments in the northern Adriatic Sea.
AB  - Samples were collected from sea sediments at seven sites in the northern Adriatic
      Sea that included six sites next to industrial complexes and one from a tourist
      site (recreational beach). The samples were assayed for alkanes and polycyclic
      aromatic hydrocarbons. The composition of the hydrocarbon samples suggested that
      industrial pollution was present in most cases. A sample from one site was also
      grown aerobically under crude oil enrichment in order to evaluate the response of
      indigenous bacterial populations to crude oil exposure. Analysis of 16S rRNA gene
      sequences showed varying microbial biodiversity depending on the level of
      pollution--ranging from low (200 detected genera) to high (1000+ genera)
      biodiversity, with lowest biodiversity observed in polluted samples. This
      indicated that there was considerable biodiversity in all sediment samples but it
      was severely restricted after exposure to crude oil selection pressure.
      Phylogenetic analysis of putative alkB genes showed high evolutionary diversity
      of the enzymes in the samples and suggested great potential for bioremediation
      and bioprospecting. The first systematic analysis of bacterial communities from
      sediments of the northern Adriatic Sea is presented, and it will provide a
      baseline assessment that may serve as a reference point for ecosystem changes and
      hydrocarbon degrading potential--a potential that could soon gain importance due
      to plans for oil exploitation in the area.

PMID- 25857846
TI  - Role of contraction duration in inducing fast-to-slow contractile and metabolic
      protein and functional changes in engineered muscle.
AB  - The role of factors such as frequency, contraction duration and active time in
      the adaptation to chronic low-frequency electrical stimulation (CLFS) is widely
      disputed. In this study we explore the ability of contraction duration (0.6, 6,
      60, and 600 sec) to induce a fast-to-slow shift in engineered muscle while using
      a stimulation frequency of 10 Hz and keeping active time constant at 60%. We
      found that all contraction durations induced similar slowing of time-to-peak
      tension. Despite similar increases in total myosin heavy (MHC) levels with
      stimulation, increasing contraction duration resulted in progressive decreases in
      total fast myosin. With contraction durations of 60 and 600 sec, MHC IIx levels
      decreased and MHC IIa levels increased. All contraction durations resulted in
      fast-to-slow shifts in TnT and TnC but increased both fast and slow TnI levels.
      Half-relaxation slowed to a greater extent with contraction durations of 60 and
      600 sec despite similar changes in the calcium sequestering proteins
      calsequestrin and parvalbumin and the calcium uptake protein SERCA. All CLFS
      groups resulted in greater fatigue resistance than control. Similar increases in
      GLUT4, mitochondrial enzymes (SDH and ATPsynthase), the fatty acid transporter
      CPT-1, and the metabolic regulators PGC-1alpha and MEF2 were found with all
      contraction durations. However, the mitochondrial enzymes cytochrome C and
      citrate synthase were increased to greater levels with contraction durations of
      60 and 600 sec. These results demonstrate that contraction duration plays a
      pivotal role in dictating the level of CLFS-induced contractile and metabolic
      adaptations in tissue-engineered skeletal muscle.

PMID- 25857849
TI  - Experiences of family carers of people diagnosed with borderline personality
      disorder.
AB  - There is limited understanding of the experience of family carers of people
      diagnosed with borderline personality disorder (BPD). This study aimed to explore
      their experiences of being carers, their attempts to seek help for the person
      diagnosed with BPD and their own carer needs. An invitation to participate in an
      online survey was distributed to carers across multiple consumer and carer
      organizations and mental health services, by the Private Mental Health Consumer
      Carer Network (Australia) in 2011. Responses from 121 carers showed that they
      experience significant challenges and discrimination when attempting to engage
      with and seek support from health services. Comparison with consumers'
      experiences (reported elsewhere) showed that these carers have a clear
      understanding of the discrimination faced by people with this diagnosis, largely
      because they also experience exclusion and discrimination. Community carer
      support services were perceived as inadequate. General practitioners were an
      important source of support; however, they and other service providers need more
      education and training to support attitudinal change to address discrimination,
      recognize carers' needs and provide more effective support. This study provides
      the first detailed account of BPD carers' experiences across a broad range of
      support needs and interactions with community support and health services.

PMID- 25857847
TI  - Safety and Efficacy Study of the Cyclooxygenase-2 Inhibitor Parecoxib Sodium
      Applied for Postoperative Analgesia After Endo-Nasal Operation.
AB  - OBJECTIVE: To evaluate the safety and efficacy of the cyclooxygenase-2 inhibitor
      parecoxib sodium after endo-nasal operation. METHODS: Patients aged 18 to 55
      years with body mass index (BMI) <=25 and ASAI~II who were undergoing endo-nasal
      operation were randomly allocated to receive either i.v. parecoxib sodium 40 mg
      or i.v. placebo (saline) 2 mL 15 minutes before induction of anesthesia. The
      magnitude of pain was measured using the visual analogue scale (VAS) and recorded
      on awakening, then at interval of 1, 2, 4, 6, 8, 12, and 24 hours after
      operation. Safety evaluation including nausea, vomiting, dry mouth, drowsiness,
      urinary retention, respiratory depression, surgical site bleeding, and so on was
      assessed. The patients' satisfaction of the postoperative analgesia was recorded
      and compared between the 2 groups. RESULTS: A total of 64 patients were enrolled
      in the study, including 31 in parecoxib group and 33 in placebo group. The VAS
      scores at 1, 2, 4, 6, 8 hours after operation were significantly lower in
      parecoxib group than in placebo group (P < 0.05). The P values were 0.002,
      <0.001, 0.001 at 2, 4, 6 hours after operation, respectively. The percentage of
      the patients who considered the postoperative analgesia "good" or "excellent" was
      45.2% in parecoxib group and 9.1% in placebo group. There were no serious side
      effects in both groups. CONCLUSIONS: Parecoxib sodium was effective and safe when
      used for postoperative analgesia in endo-nasal operation.

PMID- 25857850
TI  - Epitope-based peptide vaccine design and target site depiction against Ebola
      viruses: an immunoinformatics study.
AB  - Ebola viruses (EBOVs) have been identified as an emerging threat in recent year
      as it causes severe haemorrhagic fever in human. Epitope-based vaccine design for
      EBOVs remains a top priority because a mere progress has been made in this
      regard. Another reason is the lack of antiviral drug and licensed vaccine
      although there is a severe outbreak in Central Africa. In this study, we aimed to
      design an epitope-based vaccine that can trigger a significant immune response as
      well as to prognosticate inhibitor that can bind with potential drug target sites
      using various immunoinformatics and docking simulation tools. The capacity to
      induce both humoral and cell-mediated immunity by T cell and B cell was checked
      for the selected protein. The peptide region spanning 9 amino acids from 42 to 50
      and the sequence TLASIGTAF were found as the most potential B and T cell
      epitopes, respectively. This peptide could interact with 12 HLAs and showed high
      population coverage up to 80.99%. Using molecular docking, the epitope was
      further appraised for binding against HLA molecules to verify the binding cleft
      interaction. In addition with this, the allergenicity of the epitopes was also
      evaluated. In the post-therapeutic strategy, docking study of predicted 3D
      structure identified suitable therapeutic inhibitor against targeted protein.
      However, this computational epitope-based peptide vaccine designing and target
      site prediction against EBOVs open up a new horizon which may be the prospective
      way in Ebola viruses research; the results require validation by in vitro and in
      vivo experiments.

PMID- 25857851
TI  - Graphene-based nanomaterials as molecular imaging agents.
AB  - Molecular imaging (MI) is a noninvasive, real-time visualization of biochemical
      events at the cellular and molecular level within tissues, living cells, and/or
      intact objects that can be advantageously applied in the areas of diagnostics,
      therapeutics, drug discovery, and development in understanding the nanoscale
      reactions including enzymatic conversions and protein-protein interactions.
      Consequently, over the years, great advancement has been made in the development
      of a variety of MI agents such as peptides, aptamers, antibodies, and various
      nanomaterials (NMs) including single-walled carbon nanotubes. Recently, graphene,
      a material popularized by Geim & Novoselov, has ignited considerable research
      efforts to rationally design and execute a wide range of graphene-based NMs
      making them an attractive platform for developing highly sensitive MI agents.
      Owing to their exceptional physicochemical and biological properties combined
      with desirable surface engineering, graphene-based NMs offer stable and tunable
      visible emission, small hydrodynamic size, low toxicity, and high
      biocompatibility and thus have been explored for in vitro and in vivo imaging
      applications as a promising alternative of traditional imaging agents. This
      review begins by describing the intrinsic properties of graphene and the key MI
      modalities. After which, we provide an overview on the recent advances in the
      design and development as well as physicochemical properties of the different
      classes of graphene-based NMs (graphene-dye conjugates, graphene-antibody
      conjugates, graphene-nanoparticle composites, and graphene quantum dots) being
      used as MI agents for potential applications including theranostics. Finally, the
      major challenges and future directions in the field will be discussed.

PMID- 25857852
TI  - Polymorphic rs9471643 and rs6458238 upregulate PGC transcription and protein
      expression in overdominant or dominant models.
AB  - The pepsinogen C (PGC) gene encodes a major differentiation biomarker for gastric
      mucosa and has two single nucleotide polymorphisms, rs9471643 G>C and rs6458238
      G>A, within its 5' upstream region that are involved in gastric carcinogenesis.
      However, in what genetic models the two polymorphisms modulate disease risk and
      how they relate to gastric carcinogenesis needs further study. We fitted the most
      appropriate genetic models to the PGC polymorphisms and validated their
      robustness; then with knowledge of the genetic model, we investigated the
      influence of functional variant alleles or genotypes on gene expression in vitro
      and in vivo. We confirmed that rs9471643 CG genotype was stably associated with
      reduced gastric cancer risk in complete overdominant model. This favorable CG
      genotype was also associated with reduced atrophic gastritis risk in subjects
      carrying rs6458238 AG/AA genotype. The G>C transition at rs9471643 enhanced
      promoter activity and transcription factor binding ability, and the CG genotype
      was consistently associated with elevated levels of PGC mRNA, in situ protein and
      serum protein in complete overdominant model based-analyses. Additionally,
      rs6458238 AG/AA genotype was associated with reduced atrophic gastritis risk in
      dominant model. Its favorable A allele was related to higher promoter activity
      and lower transcription factor binding ability, and the AG/AA genotype showed
      association with elevated levels of serum PGC protein in dominant model based
      analyses. Our results suggest that rs9471643 CG and rs6458238 AG/AA genotypes
      have important roles in up-regulating PGC expression, which may partially explain
      why individuals with these favorable genotypes have decreased risks of getting
      gastric cancer.

PMID- 25857853
TI  - Mobilization of hematopoietic progenitor stem cells in allogeneic setting with
      lenograstim by subcutaneous injection, in daily or twice-daily dosing: a single
      center prospective study with historical control.
AB  - BACKGROUND: Although the mobilization of hematopoietic progenitor stem cells from
      healthy donors (HDs) using granulocyte-colony-stimulating factor is widely used,
      the ideal method for the administration of the cytokine has not yet been
      determined. STUDY DESIGN AND METHODS: Seventy-five consecutive HDs received
      lenograstim (LENO) as mobilization agent. LENO was given subcutaneously at a dose
      of 10 ug/kg in a once-daily dose (ODD) every 24 hours. Results were compared with
      a historical control group of 181 HDs treated with 5 ug/kg LENO twice-daily dose
      (TDD) with a time interval of 12 hours. RESULTS: CD34+ cell concentrations
      evaluated on Day 4 and on Day 5 were 45 * 10(6) (range, 6 * 10(6) -217 * 10(6)
      )/L and 75 * 10(6) (range, 7 * 10(6) -279 * 10(6) )/L with ODD versus 36 * 10(6)
      (range, 3 * 10(6) -200 * 10(6) )/L and 55 * 10(6) (range, 3 * 10(6) -738 * 10(6)
      )/L with TDD (p = 0.067 and p = 0.001). The collected CD34+ cell counts in first
      apheresis procedure were 5.6 * 10(6)  +/- 2.9 * 10(6) and 5.7 * 10(6)  +/- 3 *
      10(6) /kg donor and recipient body weight in the ODD versus 5.4 * 10(6)  +/- 3.8
      * 10(6) and 5.3 * 10(6)  +/- 3.5 * 10(6) /kg in the TDD cohort, respectively (p =
      0.08 and p = 0.02). Five HDs (6.7%) mobilized CD34+ cells of fewer than 2 * 10(6)
      /kg recipient body weight in the ODD group compared with seven HDs (3.9%) in the
      TDD group (p = 0.3). CONCLUSIONS: Once-daily administration of LENO is at least
      as effective as twice-daily administration for the mobilization of CD34+ cells in
      HDs.

PMID- 25857854
TI  - Implicit cognitive aggression among young male prisoners: Association with
      dispositional and current aggression.
AB  - The current study explores associations between implicit and explicit aggression
      in young adult male prisoners, seeking to apply the Reflection-Impulsive Model
      and indicate parity with elements of the General Aggression Model and social
      cognition. Implicit cognitive aggressive processing is not an area that has been
      examined among prisoners. Two hundred and sixty two prisoners completed an
      implicit cognitive aggression measure (Puzzle Test) and explicit aggression
      measures, covering current behaviour (DIPC-R) and aggression disposition (AQ). It
      was predicted that dispositional aggression would be predicted by implicit
      cognitive aggression, and that implicit cognitive aggression would predict
      current engagement in aggressive behaviour. It was also predicted that more
      impulsive implicit cognitive processing would associate with aggressive behaviour
      whereas cognitively effortful implicit cognitive processing would not. Implicit
      aggressive cognitive processing was associated with increased dispositional
      aggression but not current reports of aggressive behaviour. Impulsive implicit
      cognitive processing of an aggressive nature predicted increased dispositional
      aggression whereas more cognitively effortful implicit cognitive aggression did
      not. The article concludes by outlining the importance of accounting for implicit
      cognitive processing among prisoners and the need to separate such processing
      into facets (i.e. impulsive vs. cognitively effortful). Implications for future
      research and practice in this novel area of study are indicated. 

PMID- 25857855
TI  - Election watch: access to GP services.

PMID- 25857856
TI  - [Charles Bonnet syndrome. A 45-case series].
AB  - INTRODUCTION: Charles Bonnet Syndrome (CBS) is a condition characterised by the
      presence of visual hallucinations, mainly complex, in patients with significant
      vision loss and without cognitive impairment. The rise in CBS cases is due to an
      increased life expectancy and to the development of age-related pathologies such
      as age-related macular degeneration (AMD). PATIENTS AND METHODS: We herein
      analyse the main characteristics present in 45 patients diagnosed with CBS at the
      Neuro-ophthalmology Unit in Hospital Clinico San Carlos. The patients were
      referred from the macular pathology, glaucoma and ocular surface units, as well
      as from AE, where they were diagnosed with CBS and later confirmed at the
      Multidisciplinary Unit formed by the ophthalmology, neurology and psychiatry
      services of the hospital. RESULTS: Women (66.66%) over 80 constituted 68.88% of
      the patients and mainly had AMD (37.77%). The most prevalent hallucinations
      described by the patients were of people and faces (35.55%), in colour (66.66%),
      in movement (80%), had developed over a period of 6 to 12 months (26.66%), had a
      frequency of 3 episodes per day (35.55%) and lasted between 3 to 5 minutes
      (35.55%). CONCLUSIONS: CBS is a complex disorder that requires a
      multidisciplinary approach from neurologists, psychiatrists, general
      practitioners and ophthalmologists. New studies are needed in order to understand
      its clinical presentation and behaviour, and thus improve its management.

PMID- 25857857
TI  - [Headache and functional symptoms].
AB  - INTRODUCTION: Headaches are a common reason for visiting neurology clinics. They
      have their origin in a variety of causes and their specific diagnosis
      deteriorates as it overlaps with other chronic painful pathologies. Somatic
      functional syndromes are characterised by chronic painful conditions that have a
      negative effect on quality of life, and are accompanied by functional symptoms
      with no organic cause. AIMS: The aim of this study is to evaluate the prevalence
      of functional symptoms in patients who visited due to headaches. PATIENTS AND
      METHODS: The sample included all the patients who visited the walk-in neurology
      clinic because of headaches between March and September 2014. A semi-structured
      survey was carried out in order to evaluate obsessive personality traits,
      bruxism, gastrointestinal symptoms, anxiety, depression and sleep disorders.
      RESULTS: During the period under study, 125 patients visited due to headache. In
      all, 68.7% of patients with migraine presented functional symptoms and only 32.7%
      in the case of other headaches (p = 0.0001). CONCLUSIONS: Functional symptoms
      were prevalent in patients with headache, mainly in those with migraine.

PMID- 25857858
TI  - [What kind of health information search the spinal cord injured patients from
      Spain on the internet?].
AB  - INTRODUCTION: Internet is an alternative for health education to the population.
      Spinal cord injured individuals usually consult the Internet about their health
      problems. AIM: To identify the health information sources, the more consulted
      items and the confidence in Internet information of a group of spinal cord
      injured individuals from Spain. PATIENTS AND METHODS: A survey to spinal cord
      injured individuals from Spain was conducted, with a questionnaire in Google
      Drive. It was accessible with a link in ASPAYM-Asturias web page. The
      questionnaire included epidemiological data and information about Internet use
      and confidence in its contents. RESULTS: 121 individuals answered the survey, 64%
      male, with an average age of 45 years. The predominant aetiology was traumatic
      (70%) and 72% were paraplegics. 83% prefer to consult health care providers
      directly. More of 70% of the sample searches health problems on the Internet,
      mostly web pages in Spanish. The preferred item was 'orthopaedic materials and
      wheelchairs'. 27% of the sample trusts in the Internet information and 32% don't.
      CONCLUSIONS: This research provides information about Internet use of spinal cord
      injured individuals in Spain. Although we have to admit some bias in the study,
      more than 70% of the sample searches health problems on the Internet, mostly web
      pages in Spanish. About one in four individuals trust in information from
      Internet and most of the sample prefers recommendations directly from healthcare
      professionals.

PMID- 25857859
TI  - [Recurring post-traumatic growing skull fracture].
AB  - INTRODUCTION: Growing skull fracture, also known as post-traumatic bone
      absorption or leptomeningeal cyst, is a rare complication of traumatic brain
      injuries and occurs almost exclusively in children under 3 years of age. CASE
      REPORT: We report the case of a 6-month-old child who presented, two months after
      an apparently unimportant traumatic skull injury, persistence of left
      temporoparietooccipital cephalohaematoma with no other signs. A transfontanellar
      ultrasonography scan revealed a bone defect with brain herniation, and
      computerised tomography and magnetic resonance imaging also confirmed the
      existence of a growing fracture. Excision of the leptomeningeal cyst, dural
      closure and repair of the bone defect with plates and lactate material were
      performed. Three months after the operation, the patient still presented
      collection of fluid and recurrence of the growing fracture was confirmed.
      Following the second operation, a baby helmet was fitted in order to prevent
      renewed recurrences. One year after the traumatic injury occurred, the patient
      remains asymptomatic. CONCLUSIONS: Any child under 3 years of age with a post
      traumatic cephalohaematoma should be checked periodically until the full
      resolution of the collection of fluid, especially if they present a fractured
      skull. The presence of a cephalohaematoma that remains more than two weeks after
      traumatic brain injury must make us suspect a growing fracture and reparation of
      the dura mater and a cranioplasty will be needed to treat it. The use of
      resorbable material allows it to be remodelled as the patient's skull grows, but
      its fragility increases the risk of recurrence. The use of a baby helmet after
      the operation could prevent complications.

PMID- 25857860
TI  - [Management of autonomic dysfunction in Parkinson's disease].
AB  - Autonomic dysfunction is a common manifestation in patients with in Parkinson's
      disease, which can sometimes precede motor impairment. It can be expressed as
      orthostatic and postprandial hypotension, supine hypertension, hypersalivation,
      constipation, delayed gastric emptying, dyshidrosis, bladder and sexual
      dysfunction. It impairs the quality of life of patients and complicates the
      management of motor symptoms. Evidence available to treat complications is low.
      Our aim is to review the pathophysiology and clinical features of autonomic
      dysfunction in Parkinson's disease and provide a practical approach to handling
      the available evidence. 

PMID- 25857862
TI  - [Fasciculations, cramps, and statins].

PMID- 25857861
TI  - [Combined treatment with antiepileptic drugs. Andalusian Epilepsy Guide 2015].
AB  - AIMS: The aim of this study was to draw up a set of recommendations based on
      scientific evidence and in agreement with authors and reviewers, which address
      fundamental issues concerning the combination of antiepileptic drugs.
      DEVELOPMENT: A committee of 11 experts belonging to the Sociedad Andaluza de
      Epilepsia (SAdE--Andalusian Epilepsy Society), of whom seven were neurologists,
      three were neuropaediatricians and one was a neurologist-neurophysiologist, all
      of them with long experience in epilepsy, promoted a comprehensive literature
      review among 55 experts in epilepsy who were members of the SAdE, with the aim of
      searching for any evidence that might be available on diagnostic or therapeutic
      matters in epilepsy. The guidelines were set out in 35 chapters. One of the
      chapters addressed the combination of antiepileptic drugs in the treatment of
      epilepsy. Taking 77 bibliographical references and the consensus view of authors
      and reviewers as their starting point, a set of easily applicable recommendations
      were drawn up. CONCLUSIONS: Combining antiepileptic drugs in patients with
      epilepsy whose seizures are not controlled with a single drug can, on many
      occasions, result in their going back into remission. There are a series of
      factors related with the type of epilepsy and characteristics of the patient and
      with the antiepileptic drugs to be used in combination that may favour a
      successful therapeutic outcome. Over-treatment with the combination of
      antiepileptic drugs must be avoided as far as possible. The results of this
      review provide a set of recommendations regarding combined treatment with
      antiepileptic drugs, based on scientific evidence and the agreement of authors,
      that are simple, useful and easy to apply at the different levels of healthcare.

PMID- 25857863
TI  - [Neurosarcoidosis in the Pontevedra-Salnes health district].

PMID- 25857864
TI  - [On the complexity of diagnosing electrical status epilepticus during sleep].

PMID- 25857866
TI  - Proceedings of the 20(th) Annual Fall Scientific Meeting of the Sexual Medicine
      Society of North America, Miami Beach, USA, November 20-23, 2014.

PMID- 25857865
TI  - Psychotherapeutic Agents in End-Stage Renal Disease.
AB  - Patients with end-stage renal disease (ESRD) are often affected by many comorbid
      conditions, including mental health disorders. Psychiatric illness among patients
      with ESRD has been associated with increased risks for nonadherence,
      hospitalizations, suicide, and all-cause mortality. We reviewed the
      pharmacokinetic data available with psychotherapeutic agents, focusing on
      physiologic data rather than specific dosing recommendations. Unfortunately data
      regarding the pharmacokinetics, efficacy, and safety of psychotherapeutic agents
      in ESRD remain rather limited. Of the agents available, it appears that the most
      data in this patient group were found with selective serotonin reuptake
      inhibitors and benzodiazepines. Given the small number of patients enrolled in
      many of the studies and the wide inter-individual variability, it was difficult
      to interpret the significance of results in many instances. A number of agents,
      such as tricyclic antidepressants, were associated with adverse effects that
      would be imperative to avoid in patients with ESRD. Psychotherapeutic medications
      should be started at low doses and titrated carefully, while monitoring the
      efficacy and safety of each agent. 

PMID- 25857867
TI  - Leveraging Cultural Knowledge to Improve Diet and Health among Affiliated Pacific
      Islander Populations.

PMID- 25857870
TI  - Enhancing electrochemical performance by control of transport properties in
      buffer layers--solid oxide fuel/electrolyser cells.
AB  - The current work demonstrates how tailoring the transport properties of thin
      ceria-based buffer layers in solid oxide fuel or electrolyser cells can provide
      the necessary phase stability against chemical interaction at the
      electrolyte/electrode interface, while also providing radical improvements in the
      electrochemical performance of the oxygen electrode. Half cells of Ce0.8R0.2O2
      delta + 2 mol% Co buffer layers (where R = Gd, Pr) with Nd2NiO4+delta electrodes
      were fabricated by spin coating on dense YSZ electrolyte supports. Dramatic
      decreases in polarization resistance, Rp, of up to an order of magnitude, could
      be achieved in the order, Pr ? Gd < no buffer layer. The current article shows
      how this improvement can be related to increased levels of ambipolar conductivity
      in the mixed conducting buffer layer, which provides an additional parallel path
      for electrochemical reaction. This is an important breakthrough as it shows how
      electrode polarization resistance can be substantially improved, in otherwise
      identical electrochemical cells, solely by tailoring the transport properties of
      thin intermediate buffer layers. 

PMID- 25857869
TI  - Current views on chronic rejection after lung transplantation.
AB  - Chronic lung allograft dysfunction (CLAD) was recently introduced as an
      overarching term mainly to classify patients with chronic rejection after lung
      transplantation, although other conditions may also qualify for CLAD. Initially,
      only the development of a persistent and obstructive pulmonary function defect,
      clinically identified as bronchiolitis obliterans syndrome (BOS), was considered
      as chronic rejection, if no other cause could be identified. It became clear in
      recent years that some patients do not qualify for this definition, although they
      developed a chronic and persistent decrease in FEV1 , without another
      identifiable cause. As the pulmonary function decline in these patients was
      rather restrictive, this was called restrictive allograft syndrome (RAS). In the
      present review, we will further elaborate on these two CLAD phenotypes, with
      specific attention to the diagnostic criteria, the role of pathology and imaging,
      the risk factors, outcome, and the possible treatment options. 

PMID- 25857868
TI  - Intermittent Fasting and Human Metabolic Health.

PMID- 25857871
TI  - Crop plant genotyping by real-time PCR analysis of crude extracts of seeds.
AB  - Development of agricultural biotechnology requires rapid and convenient methods
      for crop plant genotyping. Real-time PCR is sensitive and reliable, and has been
      a routine technique in plant research. However, its application is limited by the
      cumbersome DNA template preparation procedures. We tested three PCR master mixes
      for direct amplification of crude seed DNA extracts without extensive
      purification. One mix had higher resistance to plant-derived PCR inhibitors and
      was shown to be applicable to various important crop plants. Furthermore, this
      method is capable of detecting single-copy genes from 2 mg pieces of seeds
      repetitively. Meanwhile, melting curve analysis could detect amplicons directly
      without electrophoresis manipulations. Taken together, this direct real-time PCR
      method provides a rapid and convenient tool for seed genotypic screening in crop
      plants. 

PMID- 25857872
TI  - Quantitative Determination of alpha-Arbutin, beta-Arbutin, Kojic Acid,
      Nicotinamide, Hydroquinone, Resorcinol, 4-Methoxyphenol, 4-Ethoxyphenol, and
      Ascorbic Acid from Skin Whitening Products by HPLC-UV.
AB  - An HPLC-UV method was developed for the quantitative analysis of nine skin
      whitening agents in a single injection. These compounds are alpha-arbutin, beta
      arbutin, kojic acid, nicotinamide, resorcinol, ascorbic acid, hydroquinone, 4
      methoxyphenol, and 4-ethoxyphenol. The separation was achieved on a reversed
      phase C18 column within 30 min. The mobile phase was composed of water and
      methanol, both containing 0.1% acetic acid (v/v). The stability of the analytes
      was evaluated at different pH values between 2.3 and 7.6, and the extraction
      procedure was validated for different types of skin whitening product matrixes,
      which included two creams, a soap bar, and a capsule. The best solvent system for
      sample preparation was 20 mM NaH2PO4 containing 10% methanol at pH 2.3. The
      analytical method was validated for accuracy, precision, LOD, and LOQ. The
      developed HPLC-UV method was applied for the quantitation of the nine analytes in
      59 skin whitening products including creams, lotions, sera, foams, gels, mask
      sheets, soap bars, tablets, and capsules. 

PMID- 25857873
TI  - Identification and Characterization of Indole and Oxindole Alkaloids from Leaves
      of Mitragyna speciosa Korth Using Liquid Chromatography-Accurate QToF Mass
      Spectrometry.
AB  - Alkaloids have been reported to be the major physiologically active constituents
      in Mitragyna. An analytical method was developed to provide an alternative, fast
      method for characterization of alkaloids from various M. speciosa samples. The
      separation was achieved using an RP octylsilyl (C8) column, MS detection, and a
      water-acetonitrile with formic acid gradient as the mobile phase. Ultra
      HPLC/quadrupole time-of-flight MS analysis and characterization were performed on
      12 corynanthe-type indole/oxindole alkaloids obtained from the leaves of M.
      speciosa Korth. The indoles and oxindoles had an open E ring with or without
      substitution occurring at the C9 position. The full single mass spectrum of
      alkaloids showed a strong signal for the protonated molecule [M+H]+. The product
      ion spectrum of mitragynine type of alkaloids showed strong response at
      m/z=174.0901 suggestive of an ion containing an odd number of nitrogen atoms
      corresponding to formula C11H12NO, which is characteristic of indole alkaloids. A
      multivariate statistical analysis technique, principal component analysis, was
      used to show discrimination between the M. speciosa samples. The results
      indicated that the analytical method is suitable for QC testing of various
      Mitragyna commercial samples and can be used to evaluate market products
      purported to contain M. speciosa.

PMID- 25857874
TI  - Discrimination of Gentiana rigescens from Different Origins by Fourier Transform
      Infrared Spectroscopy Combined with Chemometric Methods.
AB  - Gentiana rigescens ("Dian Longdan" in Chinese) medicinal plant is usually used
      for its activities of liver protection, cholagogic, anti-inflammatory, anti
      fungal, anti-hyperthyroidism, anti-hypertension, hyperglycemia, and relieving
      spasm and pain. In this study, methods for the discrimination of different
      geographical origins of G. rigescens by FTIR spectroscopy in hyphenation with
      chemometric methods were developed. Different pretreatments including standard
      normal variate, multiplicative scatter correction, first or second derivative,
      Savitzky-Golay filter, and Norris derivative filter were applied on the spectra
      to optimize the calibrations. According to spectrum SD, spectrum ranges (3559
      2709 and 2026-756 cm(-1)) were selected, and principal component analysis
      Mahalanobis distance (PCA-MD) model was built [the cumulative contribution rate
      of the first 10 principal components, determination coefficient (R2), root-mean
      square error of calibration (RMSEC), and root-mean-square error of prediction
      (RMSEP), and prediction accuracy were 96.4%, 98.6%, 0.5031, 0.7758, and 96.23%,
      respectively]. The spectral regions (3791-3442, 3043-2765, and 2013-646 cm(-1))
      were selected by using the variable importance in projection, and partial least
      squares discriminant analysis (PLS-DA) model was built (the cumulative
      contribution rate of the first 10 principal components, R2, RMSEC, RMSEP, and
      prediction accuracy were 91.3%, 92.0%, 0.1171, 0.1806, and 100%, respectively).
      This research showed that FTIR spectroscopy in combination with chemometrics
      methods (PCA-MD and PLS-DA) was suitable for the discrimination of different
      geographical origins of G. rigescens. Furthermore, it was found that PLS-DA
      provided better results than PCA-MD.

PMID- 25857875
TI  - Development and Validation of a Stability Indicating RP-HPLC Method for
      Hydrocortisone Acetate Active Ingredient, Propyl Parahydroxybenzoate and Methyl
      Parahydroxybenzoate Preservatives, Butylhydroxyanisole Antioxidant, and Their
      Degradation Products in a Rectal Gel Formulation.
AB  - A stability indicating method was established through a stress study, wherein
      different methods of degradation (oxidation, hydrolysis, photolysis, and
      temperature) were studied simultaneously to determine the active ingredient
      hydrocortisone acetate, preservatives propyl parahydroxybenzoate, and methyl
      parahydroxybenzoate, antioxidant butylhydroxyanisole (BHA), and their degradation
      products in a semisolid dosage gel form. The proposed method was suitably
      validated using a Zorbax SB-Phenyl column and gradient elution. The mobile phase
      consisted of a mixture of methanol, acetonitrile, and water in different
      proportions according to a planned program at a flow rate of 1.5 mL/min. The
      diode array detector was set at 240 nm for the active substance and two
      preservatives, and 290 nm for BHA. The validation study was conducted according
      to International Conference on Harmonization guidelines for specificity,
      linearity, repeatability, precision, and accuracy. The method was used for QC of
      hydrocortisone acetate gel and for the stability studies with the aim of
      quantifying the active substance, preservatives, antioxidant, and degradation
      products. It has proved to be suitable as a fast and reliable method for QC. 

PMID- 25857876
TI  - Validated stability-indicating spectrophotometric methods for the determination
      of cefixime trihydrate in the presence of its acid and alkali degradation
      products.
AB  - Five simple, accurate, precise, and economical spectrophotometric methods have
      been developed for the determination of cefixime trihydrate (CFX) in the presence
      of its acid and alkali degradation products without prior separation. In the
      first method, second derivative (2D) and first derivative (1D) spectrophotometry
      was applied to the absorption spectra of CFX and its acid (2D) or alkali (1D)
      degradation products by measuring the amplitude at 289 and 308 nm, respectively.
      The second method was a first derivative (1DD) ratio spectrophotometric method
      where the peak amplitudes were measured at 311 nm in presence of the acid
      degradation product, and 273 and 306 nm in presence of its alkali degradation
      product. The third method was ratio subtraction spectrophotometry where the drug
      is determined at 286 nm in laboratory-prepared mixtures of CFX and its acid or
      alkali degradation product. The fourth method was based on dual wavelength
      analysis; two wavelengths were selected at which the absorbances of one component
      were the same, so wavelengths 209 and 252 nm were used to determine CFX in
      presence of its acid degradation product and 310 and 321 nm in presence of its
      alkali degradation product. The fifth method was bivariate spectrophotometric
      calibration based on four linear regression equations obtained at the wavelengths
      231 and 290 nm, and 231 and 285 nm for the binary mixture of CFX with either its
      acid or alkali degradation product, respectively. The developed methods were
      successfully applied to the analysis of CFX in laboratory-prepared mixtures and
      pharmaceutical formulations with good recoveries, and their validation was
      carried out following the International Conference on Harmonization guidelines.
      The results obtained were statistically compared with each other and showed no
      significant difference with respect to accuracy and precision.

PMID- 25857877
TI  - Identification of Radiodegradation Products of Acebutolol and Alprenolol by
      HPLC/MS/MS.
AB  - Two therapeutically active compounds from the group of beta-blockers, acebutolol
      (AC) and alprenolol (AL), in solid form were subjected to ionizing radiation
      emitted by a beam of high energy electrons from an accelerator with a standard
      sterilization dose of 25 kGy and in higher doses of 50-400 kGy. The effects of
      irradiation were detected by chromatographic methods (TLC, HPLC) and a hyphenated
      method (HPLC/MS/MS). No significant changes in the physicochemical properties of
      both compounds studied irradiated with 25 kGy were noted, but upon irradiation
      with the highest dose (400 kGy) the loss of AC and AL content determined by HPLC
      was 2.79 and 9.12%, respectively. The product of AC decomposition and the two
      products of AL decomposition were separated and identified by HPLC/MS/MS. It has
      been established that radiodegradation of AC and AL takes place by oxidation,
      leading to formation of the products of radiolysis, most probably alcohol
      derivatives of the beta-blockers studied. The additional product that appears on
      radiodegradation of AL is probably formed as a result of two simultaneous
      reactions: oxidation and CH2 group elimination. 

PMID- 25857878
TI  - Measurement Uncertainty of Chromogenic LAL Assays: Reaction Time and Proportion
      of Endotoxin and LAL Reagent Affect Release of p-Nitroaniline.
AB  - Limulus Amebocyte Lysate (LAL) assays are widely used for detection and
      quantification of bacterial endotoxins in pharmaceuticals and medical devices.
      However, there are only a few studies on the measurement uncertainty of LAL
      assays. The aim of this work was to identify and quantify the main sources of
      measurement uncertainty for end point and kinetic-chromogenic LAL assays.
      Response surface methodology was used to study how the release of p-nitroaniline
      (pNA) is affected by reaction time and proportion of endotoxin and LAL reagent in
      end point and kinetic-chromogenic LAL assays, respectively. Increased release of
      pNA was observed when reaction time was increased. In addition, if different
      volumes of sample (or endotoxin standard) and LAL reagent are used, the pNA
      release rate will be affected. These results may be due to the increased
      interaction between the bacterial endotoxin and LAL-activated enzyme. Final
      measurement uncertainties (95% confidence interval) were 90-120% and 90-127% of
      bacterial endotoxin content for end point and kinetic-chromogenic assays,
      respectively. These values are reasonable for the scope of the method and allow
      the application of these measurement uncertainties in routine analysis of
      pharmaceuticals and medical devices. 

PMID- 25857879
TI  - Simultaneous Determination of Tramadol and its Metabolite in Human Plasma by
      GC/MS.
AB  - A simple and sensitive GC/MS method for the determination of tramadol and its
      metabolite (O-desmethyltramadol) in human plasma was developed and validated.
      Medazepam was used as an internal standard. The calibration curves were linear
      (r=0.999) over tramadol and O-desmethyltramadol concentrations ranging from 10 to
      200 ng/mL and 7.5 to 300 ng/mL, respectively. The method had an accuracy of >95%
      and intra- and interday precision (RSD%) of <=4.83% and <=4.68% for tramadol and
      O-desmethyltramadol, respectively. The extraction recoveries were 97.6+/-1.21%
      and 96.3+/-1.66% for tramadol and O-desmethyltramadol, respectively. The LOQ
      using 0.5 mL human plasma was 10 ng/mL for tramadol and 7.5 ng/mL for O
      desmethyltramadol. Stability studies showed that tramadol and O-desmethyltramadol
      were stable in human plasma after 8 h incubation at room temperature or after 1
      week storage at -20 degrees C with three freeze-thaw cycles. Also, this method
      was successfully applied to six patients who had been given an intravenous
      formulation of 100 mg tramadol with Cmax results of 2018.1+/-687.8 and 96.1+/
      22.7 ng/mL for tramadol and O-desmethyltramadol, respectively.

PMID- 25857880
TI  - Dai Nippon Printing Co., Ltd Medi.Ca CC for Enumeration of Coliform Bacteria.
AB  - A ready-made dry medium method for coliform count, the Medi.Ca CC method, was
      compared to the Violet Red Bile Agar method (Bacteriological Analytical Manual,
      Chapter 4, Enumeration of Escherichia coli and the Coliform Bacteria, Section G)
      for nine raw foods from four food categories: raw ground pork, raw lamb, raw
      ground chicken, raw tuna fillet, raw salmon fillet, raw shrimp, fresh peeled
      banana, fresh cut pineapple, and fresh cut apple. The 95% confidence interval for
      the mean difference between the two methods at each contamination level for seven
      matrixes from all four categories fell within the range of -0.50 to 0.50, and no
      statistical difference was observed at all three contamination levels for four
      matrixes from three categories. These results demonstrated that the Medi.Ca CC
      method is a reasonable alternative to the reference method for raw meat, raw
      poultry, raw fish, and fresh fruits. 

PMID- 25857881
TI  - InstantLabs(r) E. coli O157 Food Safety Kit.
AB  - The InstantLabs(r) E. coli O157 Food Safety Kit was validated against the
      International Organization for Standardization reference method 16654 for the
      detection of Escherichia coli O157. The matrixes, raw ground beef, raw beef trim,
      Romaine lettuce, pasteurized apple juice, and raw ground chicken, were inoculated
      with appropriate CFU/test portion of E. coli O157 to generate fractional
      positives (5-15) in 20 inoculated samples. The matrixes were co-inoculated with
      Salmonella at 2-5 times the level of E. coli O157 to demonstrate the potential
      for using the same enrichment culture for the detection of multiple organisms.
      Samples were enriched in prewarmed FASTGRO SE broth at 42+/-1 degrees C for 10-20
      h. All samples were confirmed using the ISO reference method, regardless of
      initial screen result. The InstantLabs test method performed as well as or better
      than the reference method for the detection of E. coli O157 in all tested
      samples. Inclusivity and exclusivity testing revealed no false negatives and no
      false positives among the 50 E. coli O157 serovars and 30 non-E. coli O157
      species examined. Finally, the method was shown to be robust when variations were
      applied to enrichment time, volume for DNA extraction, and heat block time.

PMID- 25857882
TI  - A Natural and Concurrent Interferent in Bolinus brandaris with Consequences on
      Amnesic Shellfish Poisoning Risk Management.
AB  - Regulations aimed to protect public health from amnesic shellfish poisoning (ASP)
      are focused on the detection and accurate quantification of domoic acid (DA). The
      reference detection determination used by the different shellfish safety
      monitoring agencies worldwide is HPLC separation followed by UV detection, in
      which different chromatographic column lengths or brands are accepted as long as
      it is C18 column. A laboratory validation of this method showed different
      performance of two accepted chromatographic columns when analyzing Bolinus
      brandaris samples. A natural compound, present only in those samples that
      contained DA, was evidenced by one of the columns. The DA quantification obtained
      with the column that coelutes both compounds was approximately twice the amount
      obtained with the column that separates them. This difference has important
      consequences in the ASP toxins management for this fishery. The identity and
      toxicity of the compound are still unknown. 

PMID- 25857883
TI  - QuickToxTM Kit for QuickScan DON3 (Vomitoxin) Method Modification.
AB  - Lateral flow technology and a reader-based system are used for quantitative
      determination of deoxynivalenol (DON), also known as vomitoxin, residues in
      cereal grain commodities by the QuickTox Kit for QuickScan DON (Vomitoxin). The
      assay has been modified, and a study was conducted in support of a Performance
      Tested MethodSM (PTM) Modification. The modified assay employs identical biologic
      reagents as used previously (PTM No. 121202). Compared to the PTM certified
      product, the new assay uses modified device architecture. Multiple kits and
      catalog numbers were required in the original kit reflecting the necessity for
      matrix specific calibration curves affixed to assay strips. A single calibration
      curve and kit are utilized in the new product; extraction volumes used in sample
      preparation are varied to accommodate multiple sample types. Extracts are
      clarified by filtration or settling depending on the sample type. Filtration was
      used for matrixes examined in these studies. With the original product, the
      extract was mixed 1:1 with DB1 buffer followed by the addition of the strip which
      was developed for 10 min. The new product dilutes extracts five-fold offline in
      DB6 buffer; an aliquot of the dilution is moved to a reaction vial followed by
      strip development time for 3 min. The new assay performance was evaluated for
      linearity, robustness, selectivity (inclusivity), lot-to-lot consistency, and
      both internal and third party matrix studies. All DON positive samples yielded
      results within previously defined acceptable ranges with dose-dependent
      correlation values of R2 greater than 0.97 in linearity and internal and external
      matrix studies. Inclusivity data indicated detection of DON along with acetyl
      derivatives, glucoside-conjugate, and Nivalenol. Robustness studies showed within
      range results upon co-variation of multiple user interface parameters, and lot-to
      lot consistency challenges demonstrated acceptable results across five
      manufactured lots.

PMID- 25857884
TI  - Ultra-High Performance Liquid Chromatography (UHPLC) Method for the Determination
      of Limonene in Sweet Orange (Citrus sinensis) Oil: Implications for Limonene
      Stability.
AB  - The citrus-derived bioactive monoterpene limonene is an important industrial
      commodity and fragrance constituent. An RP isocratic elution C18 ultra-HPLC
      (UHPLC) method using a superficially porous stationary phase and photodiode array
      (PDA) detector has been developed for determining the limonene content of sweet
      orange (Citrus sinensis) oil. The method is fast with a cycle time of 1.2 min,
      linear, precise, accurate, specific, and stability indicating, and it satisfies
      U.S. Pharmacopeia suitability parameters. The method may be useful in its present
      form for limonene processing, or modified for research on more polar compounds of
      the terpenome. A forced-degradation experiment showed that limonene is degraded
      by heat in hydro-ethanolic solution. PDA detection facilitates classification of
      minor components of the essential oil, including beta-myrcene. 

PMID- 25857885
TI  - Validated HPLC-Diode Array Detector Method for Simultaneous Evaluation of Six
      Quality Markers in Coffee.
AB  - Nicotinic acid, N-methylpyridinium ion, and trigonelline are well studied
      nutritional biomarkers present in coffee, and they are indicators of thermal
      decomposition during roasting. However, no method is yet available for their
      simultaneous determination. This paper describes a rapid and validated HPLC-diode
      array detector method for the simultaneous quantitation of caffeine,
      trigonelline, nicotinic acid, N-methylpyridinium ion, 5-caffeoylquinic acid, and
      5-hydroxymethyl furfural that is applicable to three coffee matrixes: green,
      roasted, and instant. Baseline separation among all compounds was achieved in 30
      min using a phenyl-hexyl RP column (250*4.6 mm, 5 MUm particle size), 0.3%
      aqueous formic buffer (pH 2.4)-methanol mobile phase at a flow rate of 1 mL/min,
      and a column temperature at 30 degrees C. The method showed good linear
      correlation (r2>0.9985), precision (less than 3.9%), sensitivity (LOD=0.023-0.237
      MUg/mL; LOQ=0.069-0.711 MUg/mL), and recovery (84-102%) for all compounds. This
      simplified method is amenable for a more complete routine evaluation of coffee in
      industry.

PMID- 25857886
TI  - Gluten in Rice Flour and Baked Rice Products by G12 Sandwich ELISA: First Action
      2014.03.
AB  - The Protein and Enzymes Technical Committee of American Association of Cereal
      Chemists initiated a collaborative study to confirm whether the G12 antibody
      based sandwich ELISA test kit is able to detect gluten in the lower mg/kg (ppm)
      level. Twenty laboratories investigated 24 heat-treated and non-heat-treated
      blind-coded samples with incurred gluten levels up to 100 mg/kg. The method has
      been validated for testing foods to conform to the defined Codex thresholds for
      gluten in gluten-free products at less than 20 mg gluten/kg. The collaborative
      study showed that low levels of gluten could be detected by G12 Sandwich ELISA
      with reproducibility RSDR of 32% and repeatability RSDr of 16%. Incurred samples
      showed a recovery between 62 and 135%. It is recommended that the method be
      accepted by AOAC as Official First Action. 

PMID- 25857887
TI  - Evaluation Protocol for Review of Method Validation Data by the AOAC Stakeholder
      Panel on Infant Formula and Adult Nutritionals Expert Review Panel.
AB  - Methods under consideration as part of the AOAC Stakeholder Panel on Infant
      Formula and Adult Nutritionals process are to be evaluated against a set of
      Standard Method Performance RequirementsSM (SMPRs) via peer review by an expert
      review panel (ERP). A validation protocol and a checklist have been developed to
      assist the ERP to evaluate experimental data and to compare multiple candidate
      methods for each nutrient. Method performance against validation parameters
      mandated in the SMPRs as well as additional criteria are to be scored, with the
      method selected by the ERP proceeding to multilaboratory study prior to Final
      Action approval. These methods are intended to be used by the infant formula
      industry for the purposes of dispute resolution.

PMID- 25857888
TI  - Modified screen-printed ion selective electrodes for potentiometric determination
      of sodium dodecylsulfate in different samples.
AB  - Fabrication and general performance characteristics of novel screen-printed
      sensors for potentiometric determination of sodium dodecylsulfate (SDS) are
      described. The sensors are based on the use of ion-association complexes of SDS
      with cetylpyridinium chloride (electrode I) and cetyltrimethylammonium bromide
      (electrode II) as exchange sites in a screen-printed electrode matrix. Electrodes
      (I) and (II) show fast, stable, and near-Nernstian response for the mono-charge
      anion of SDS over the concentration range of 1*10(-2) - 5.8*10(-7) and 1*10(-2)
      6.3*10(-7) mol/L at 25 degrees C and the pH range of 2.0-9.0 and 2.0-8.0 with
      anionic slope of 57.32+/-0.81 and 56.58+/-0.65 mV/decade, respectively.
      Electrodes (I) and (II) have lower LODs of 5.8*10(-7) and 6.3*10(-7) mol/L and
      response times of about 8 and 13 s, respectively. Shelf life of 5 months for both
      electrodes is adequate. Selectivity coefficients of SDS related to a number of
      interfering cations, and some inorganic compounds were investigated. There were
      negligible interferences caused by most of the investigated species. The direct
      determination of 0.10-13.50 mg of SDS by electrodes (I) and (II) shows average
      recoveries of 99.96 and 99.85%, and mean RSDs of 0.83 and 1.04%, respectively. In
      the present investigation, both electrodes were used successfully as end point
      indicators for determination of SDS in pure pharmaceutical preparations and real
      spiked water samples. The results obtained using the proposed sensors to
      determine SDS in solution compared favorably with those obtained by the standard
      addition method.

PMID- 25857889
TI  - Immobilized Coprinus plicatilis Biodegradation of Fluorene in Two Different
      Packed-Bed Reactors.
AB  - The biodegradation of fluorene by immobilized Coprinus plicatilis was studied in
      pinewood and foam glass bead-packed reactors. The reactors were operated in a
      sequencing batch system. Removal efficiency increased over time and elevated
      influent fluorene concentration (85 mg/L) was removed 100% in 24-30 h batch
      cycles. Increased laccase activity was detected with the introduction of the
      compounds, and optimum activity corresponded to optimum removal periods.
      Significantly higher laccase activity (16.7-19 U/L) was detected in the glass
      bead-packed reactor compared to the pinewood-packed reactor (0.2-5 U/L). The
      presence of Mn2+ ions in the wood material possibly caused elevated manganese
      peroxidase activity (0.3-5.8 U/L) compared to low to negligible activity in the
      glass bead reactor. Reactor performances are discussed in relation to sequencing
      batch operation and nutrient requirements necessary to induce and sustain fungal
      enzyme activity in inert-like organic material packed systems. Biodegradation
      metabolites were detected in samples via GC/MS.

PMID- 25857890
TI  - High-Throughput Analytical Techniques for Multiresidue, Multiclass Determination
      of 653 Pesticides and Chemical Pollutants in Tea-Part IV: Evaluation of the
      Ruggedness of the Method, Error Analysis, and Key Control Points of the Method.
AB  - A 3 month study was conducted on the ruggedness of a multiresidue method for
      accuracy and stability. The results indicate that in terms of Youden pair ratios
      of 201 pesticide aged tea samples falling approximately within 1.00-1.20 of the
      ratio of theoretical spraying concentrations, the differences do not exceed 5%
      for percentages made up by ratios of the fixed values obtained by two kinds of
      instruments for two teas and those made up by 18 circular determinations.
      However, regarding two kinds of SPE cartridges, the Cleanert TPT cartridge is
      higher than the ENVI-CARB+primary secondary amine (PSA) cartridge by 10%.
      Pertaining to RSD values of "parallel samples" and whether it is green tea or
      Woolong tea, the percentages of RSD<=15% values of the parallel samples all
      exceed 88%. Whether it is the first or circular determination for two teas and
      analytical results from two kinds of instruments, the percentages of RSD<=15%
      values have a difference of less than 6%, while the TPT cartridge is better than
      ENVI-CARB+PSA by above 6% for the two cartridges. Concerning RSDs of Youden pair
      ratios, RSD<=15% values have a proportion exceeding 85% for both green tea and
      Woolong tea, and the percentage is greater than 87% whether it is for two kinds
      of SPE cartridges or two kinds of instruments. In terms of Youden pair ratios and
      the classified statistical analysis of the ruggedness data of parallel samples,
      the proportion of RSD<=15% values of Youden pair ratios is 8% higher for the TPT
      cartridge than the ENVI-CARB+PSA cartridge; the proportion of RSD<=15% values of
      parallel samples is 6.2% higher for the TPT cartridge than the ENVI-CARB+PSA
      cartridge. Data show no marked differences for two teas and two kinds of
      instruments. A comparison of the aforementioned aspects finds that good
      ruggedness was obtained with both SPE cleanup methods, and the results from the
      TPT cartridge are better than those from the ENVI-CARB+PSA cartridge.

PMID- 25857891
TI  - High-Throughput Analytical Techniques for Determination of Residues of 653
      Multiclass Pesticides and Chemical Pollutants in Tea--Part V: A Comparative Study
      of the Influence of Tea Hydration on the Efficiency of Pesticide Multiresidue
      Determination Using Three Sample Preparation Methods and GC/MS/MS.
AB  - This paper describes a comparative study of the influence of three sample
      preparation techniques (M1: hydration+oscillating extraction+partial extraction
      solution hexane partitioning cleanup; M2: hydration+oscillating
      extraction+overall extraction solution SPE cleanup; and M3: pure acetonitrile
      homogeneous extraction+overall extraction SPE cleanup) on the determination
      efficiency of 456 pesticide multiresidues in tea. First, it was discovered from
      the mathematical correlation equation of 329 pesticide recoveries established and
      log Kow values that the extraction efficiency of hydration method M1 has obvious
      correlation with pesticide log Kow, making the extraction efficiency of M1 take
      the shape of an arc trend line with a certain arc hanging down from both ends of
      polar pesticides and nonpolar pesticides. Second, regarding the M1 method, the
      interfering matter after co-extraction increased in large quantities, which
      markedly lowered the S/N of the target pesticides and method sensitivity, leading
      to an obvious decrease of the method efficiency. The fortification experiment of
      the uniform limit 0.010 mg/kg proved that with the M1 hydration method there are
      23 pesticides with recoveries between 70 and 120% and RSD<20%, accounting for
      only 5.0%, while with nonhydration method M3 there are 229 pesticides, making up
      50%.

PMID- 25857892
TI  - Determination of arsenic, chromium, lead, manganese, and mercury in certifiable
      color additives by inductively coupled plasma/mass spectrometry.
AB  - Specifications in the Code of Federal Regulations limit the levels of As, Pb, and
      Hg in most certifiable color additives, and some have additional specification
      limits for Cr and Mn. A new ICP/MS method was developed and validated for the
      quantitative determination of these elements in various certifiable color
      additives. One dissolution and two microwave-assisted digestion sample
      preparation procedures were optimized to address initial low Hg and enhanced As
      recoveries. Results using the three sample preparation procedures were generally
      equivalent for all of the elements determined. LOQ values were 0.3 mg/kg for As,
      0.7 mg/kg for Cr, 0.4 mg/kg for Pb, 0.7 mg/kg for Mn, and 0.1 mg/kg for Hg. 

PMID- 25857893
TI  - Flame Atomic Absorption Spectrometric Determination of Trace Metal Ions in
      Environmental and Biological Samples After Preconcentration on a Newly Developed
      Amberlite XAD-16 Chelating Resin Containing p-Aminobenzene Sulfonic Acid.
AB  - Amberlite(r) XAD-16 was functionalized with p-aminobenzene sulfonic acid via an
      azo spacer in order to prepare a new chelating resin, which was then
      characterized by water regain value, hydrogen ion capacity, elemental analyses,
      and IR spectral and thermal studies. The maximum uptake of Cu(II), Ni(II),
      Zn(II), Co(II), Cr(III), Fe(III), and Pb(II) ions was observed in the pH range
      4.0-6.0 with the corresponding half-loading times of 6.5, 7.0, 8.0, 9.0, 11.0,
      8.5, and 16.5 min. The sorption data followed Langmuir isotherms and a pseudo
      second-order model. Thermodynamic quantities, DeltaH and DeltaS, based on the
      variation of the distribution coefficient with temperature were also evaluated.
      High preconcentration factors of 60-100 up to a low preconcentration limit of 4.0
      6.6 MUg/L have been achieved for the metal ions. The validity of the method was
      checked by analyzing standard reference materials and recoveries of trace metals
      after spiking. The analytical applications of the method were explored by
      analyzing natural water, mango pulp, mint leaves, and fish.

PMID- 25857894
TI  - Experimental design methodology applied to mercury determination: hair samples as
      a mercury bioindicator.
AB  - The application of modified magnetic nanoparticles in extraction of trace Hg was
      investigated. For this purpose, surfaces of magnetic nanoparticles were modified
      by 2-picolamine and then utilized as a solid-phase sorbent for Hg(II) extraction.
      A statistical method, based on surface response design, has been used for the
      optimization of Hg ion elution from the magnetic nanoparticles. The sorbed Hg
      ions were eluted quantitatively with 5.5 mL of a solution containing 0.8 M HCl
      and 0.08 M EDTA after 12 min. The recovery value in this method was 98.6% with
      RSD of 1.4%, and the obtained LOD was 0.01 ng/mL. The preconcentration factor was
      calculated to be 179. The method was applied to the determination of hair Hg
      content for biomonitoring purposes. 

PMID- 25857895
TI  - Application of Near Infrared Spectroscopy Coupled with Fluidized Bed Enrichment
      and Chemometrics to Detect Low Concentration of beta-Naphthalenesulfonic Acid.
AB  - A fluidized bed enrichment technique was developed to improve sensitivity of near
      infrared (NIR) spectroscopy with features of rapidness and large volume solution.
      D301 resin was used as an adsorption material to preconcentrate beta
      naphthalenesulfonic acid in solutions in a concentration range of 2.0-100.0
      MUg/mL, and NIR spectra were measured directly relative to the beta
      naphthalenesulfonic acid adsorbed on the material. An improved partial least
      squares (PLS) model was attained with the aid of multiplicative scatter
      correction pretreatment and stability competitive adaptive reweighted sampling
      wavenumber selection method. The root mean square error of cross validation was
      1.87 MUg/mL at PLS factor of 7. An independent test set was used to assess the
      model, with the relative error (RE) in an acceptable range of 0.46 to 10.03% and
      mean RE of 3.72%. This study confirmed the viability of the proposed method for
      the measurement of a low content of beta-naphthalenesulfonic acid in water.

PMID- 25857896
TI  - Synthesis and chelation properties of a new polymeric ligand derived from 1-amino
      2-naphthol-4-sulfonic Acid.
AB  - A novel chelating resin for preconcentration of heavy metals from various
      seawater samples has been developed by condensing 1-amino-2-hydroxy-7-[(4
      hydroxyphenyl)diazenyl] naphthalene-4-sulfonic acid (AHDNS) with formaldehyde
      (1:2 mole ratio) in the presence of oxalic acid as the catalyst. The resin thus
      obtained was used as a solid sorbent for the separation of divalent metal ions
      present at trace levels in seawater. The functionalized phenol (AHDNS) was
      characterized by spectral studies. The polymeric resin AHDNS-formaldehyde (AHDNS
      F) obtained by condensing the functionalized phenol and formaldehyde was
      characterized by IR and NMR spectral studies. The chelating property of the AHDNS
      F resin towards divalent metal ions was studied as a function of pH and in the
      presence of electrolyte. The metal uptake properties of the resin were determined
      by using an atomic absorption spectrophotometer. This procedure was validated for
      recovery of divalent metal ions from seawater samples. The recoveries of cadmium,
      cobalt, copper, manganese, lead, and zinc were above 92% under the optimum
      preconcentration conditions. The LOD was <0.73 MUg/L and the RSDs were <2%. Thus,
      the AHDNS-F resin can be widely used as a solid sorbent for the preconcentration
      of trace metals at ppm levels in seawater samples. 

PMID- 25857897
TI  - Development and validation of one-step ultrasound-assisted extraction for
      simultaneous determination of multiclass fungicides in soils.
AB  - A rapid, efficient, and simple one-step ultrasound-assisted extraction (UAE)
      method was developed for the analysis of seven fungicides (cymoxanil, metalaxyl,
      mandipropamid, folpet, chlorothalonil, kresoxim-methyl, and famoxadone) in
      horticultural soils. Analytes in the samples were determined by HPLC with
      variable wavelength detection. Key parameters that influence the UAE procedure
      were optimized, such as the nature and volume of extraction solvent, number of
      sonication steps, and sonication time. The highest extraction efficiencies in the
      range of 61.1-87.8% were obtained by using only 7.5 mL of ethyl acetate-hexane
      (1+1, v/v) and sonicating for 10 min. At 0.5 and 2.0 MUg/g fortification levels,
      satisfactory recoveries (>60%) with RSD<13% were obtained for each analyte,
      except for folpet (>52%). The method was linear over the range of 0.005 to 10
      MUg/g and the correlation coefficients (r2) obtained ranged from 0.9955 to
      0.9992. The LODs (S/N=3) varied from 0.0015 to 0.006 MUg/g. The proposed UAE
      procedure was compared to classical extractions (shake-flask and Soxhlet
      extraction) and showed satisfactory extraction efficiencies using shorter time
      and smaller amounts of organic solvents, thereby minimizing the costs of the
      analysis and the disposal of waste solvent.

PMID- 25857898
TI  - Selective ligandless cloud point extraction of palladium from water and dust
      samples.
AB  - In this study, the phase-separation phenomenon of non-ionic surfactants was used
      for separation and preconcentration of Pd(II). The cloud point extraction (CPE)
      method is based on the formation of PdI2 which is then entrapped in the non-ionic
      surfactant Triton X-114. Ethanol acidified with 0.5 M HNO3 was added to the
      surfactant-rich phase prior to its analysis by flame atomic absorption
      spectrometry. The main factors affecting CPE efficiency, such as sample solution
      pH, concentration of iodide ion and Triton X-114, equilibration temperature and
      time, were all investigated and optimized. At optimum conditions, a calibration
      curve was constructed for the determination of palladium according to the
      ligandless CPE procedure. Linearity was maintained between 1.0 to 500.0 ng/mL.
      The LOD based on three times the SD of the blank divided by the slope of
      analytical curve, (3Sb/m) was 0.3 ng/mL. Seven replicate determinations of a
      solution containing of 4.0 MUg palladium gave a mean absorbance of 0.359 with
      RSD+/-1.85%. The high efficiency of CPE to carry out the determination of
      palladium in complex matrixes was demonstrated. The proposed method has been
      applied to the determination of trace amounts of palladium in a platinum-iridium
      alloy, water, and dust samples, with satisfactory results.

PMID- 25857899
TI  - Selective Solid-Phase Extraction of Zinc(II) from Environmental Water Samples
      Using Ion Imprinted Activated Carbon.
AB  - A simple ion imprinted amino-functionalized sorbent was synthesized by coupling
      activated carbon with iminodiacetic acid, a functional compound for metal
      chelating, through cyanoric chloride spacer. The resulting sorbent has been
      characterized using FTIR spectroscopy, elemental analysis, and thermogravimetric
      analysis and evaluated for the preconcentration and determination of trace Zn(II)
      in environmental water samples. The optimum pH value for sorption of the metal
      ion was 6-7.5. The sorption capacity of the functionalized sorbent was 66.6 mg/g.
      The chelating sorbent can be reused for 10 cycles of sorption-desorption without
      any significant change in sorption capacity. A recovery of 100% was obtained for
      the metal ion with 0.5 M nitric acid as the eluent. Compared with nonimprinted
      polymer particles, the prepared Zn-imprinted sorbent showed high adsorption
      capacity, significant selectivity, and good site accessibility for Zn(II).
      Scatchard analysis revealed that the homogeneous binding sites were formed in the
      polymer. The equilibrium sorption data of Zn(II) by modified resin were analyzed
      by Langmuir, Freundlich, Temkin, and Redlich-Peterson models. Based on
      equilibrium adsorption data, the Langmuir, Freundlich, and Temkin constants were
      determined as 0.139, 12.82, and 2.34, respectively, at 25 degrees C. 

PMID- 25857900
TI  - Separation and Preconcentration of Sudan Blue II Using Membrane Filtration and UV
      Visible Spectrophotometric Determination in River Water and Industrial Wastewater
      Samples.
AB  - A new separation and preconcentration method based on adsorption on a cellulose
      acetate membrane filter and elution with ethanol was established for the UV-Vis
      spectrophotometric determination of Sudan blue II. Various analytical parameters
      such as pH of working media, flow rates of solutions, and sample volumes were
      optimized. Matrix effects of concomitants were investigated for the quantitative
      recovery values of Sudan blue II. The preconcentration factor was 200. LOD was
      calculated as 0.96 MUg/L. RSD was 5.1%. The optimized procedure was applied to
      the spectrophotometric determination of Sudan blue II in river and industrial
      wastewater samples from oil and dye products. 

PMID- 25857901
TI  - Determination of V, Cr, Cu, As, and Pb Ions in Water and Biological Samples by
      Combining ICP-MS with Online Preconcentration Using Impregnated Resin.
AB  - A method was developed for detection of V, Cr, Cu, As, and Pb in water and
      biological samples by combining online flow injection and preconcentration with
      inductively coupled plasma-MS. The 2-nitroso-1-naphthol-4-sulfonic acid (Nitroso
      S) impregnated MCI GEL CHP20P resin was prepared as an enrichment sorbent. Some
      parameters affecting the efficiency of the preconcentration process were
      investigated in the experiment, including the pH and volume of sample solution,
      the flow rate for sample loading, the type and concentration of eluent, and the
      influence of co-existing ions. Under the optimal experimental conditions, the
      enrichment factor and LOD (3s) of chosen metal ions V, Cr, Cu, As, and Pb were in
      the ranges of 71-268 and 4.89-23.76 ng/L, respectively. Based on 11 repeated
      measurements of standard solutions (1.0 MUg/L), the RSD of the ions ranged from
      1.2 to 2.9%. The detection procedure was also performed for analyzing two
      certified reference materials, GBW 08607 (water) and GBW 10052 (green tea), as
      well as environmental water and biological samples. Good agreement with certified
      values and high recoveries have demonstrated improved accuracy of the proposed
      method. 

PMID- 25857902
TI  - Accurate quantification of two key time points used in the determination of
      hydroxyl polyaluminum species by ferron timed spectrophotometry.
AB  - The content of mononuclear Al (Ala%) changed with its determination time (ta)
      under different dosages of Ferron (7-iodo-8-hydroxyquinoline-5-sulfonic acid,
      [Ferron]), and the change of Ala% with [Ferron] at different ta was
      systematically investigated for the first time. Thus, the most appropriate ta was
      found with the optimal [Ferron]. Also, the judgment of the platform (flat or
      level portion) of the complete reaction on the absorption-time curve determined
      in the hydroxyl polyaluminum solution by Ferron timed spectrophotometry (Ferron
      assay) was first digitized. The time point (tb) of complete reaction between the
      medium polyaluminum (Alb) and Ferron reagent depended on the reaction extent, and
      time could not be used only to judge. Thus, the tb was accurately determined and
      reduced to half of original, which improved the experiment efficiency
      significantly. The Ferron assay was completely optimized. 

PMID- 25857903
TI  - Multi-residue Determination of Polar Veterinary Drugs in Livestock and Fishery
      Products by Liquid Chromatography/Tandem Mass Spectrometry.
AB  - Residues of 37 polar veterinary drugs belonging to six families (quinolones,
      tetracyclines, macrolides, lincosamides, sulfonamides, and others) in livestock
      and fishery products were determined using a validated LC-MS/MS method. There
      were two key points in sample preparation. First, extraction was performed with
      two solutions of different polarity. Highly polar compounds were initially
      extracted with Na2EDTA-McIlvaine's buffer (pH 7.0). Medium polar compounds were
      then extracted from the same samples with acetonitrile containing 0.1% formic
      acid. Secondly, cleanup was performed using a single SPE polymer cartridge. The
      first extracted solution was applied to the cartridge. Highly polar compounds
      were retained on the cartridge. Then, the second extracted solution was applied
      to the same cartridge. Both highly and medium polar compounds were eluted from
      the cartridge. This method satisfied the guideline criteria for 37 out of 37
      drugs in swine muscle, chicken muscle, bovine muscle, prawn, salmon trout, red
      sea bream, milk, and honey; 35 out of 37 in egg; and 34 out of 37 in flounder.
      The LOQ ranged from 0.1 to 5 MUg/kg. Residues were detected in 24 out of 110
      samples and analyzed using the validated method. 

PMID- 25857905
TI  - Readmissions after carotid artery revascularization in the Medicare population: a
      word of caution.

PMID- 25857904
TI  - Readmissions after carotid artery revascularization in the Medicare population.
AB  - BACKGROUND: In appropriately selected patients with severe carotid stenosis,
      carotid revascularization reduces ischemic stroke. Prior clinical research has
      focused on the efficacy and safety of carotid revascularization, but few
      investigators have considered readmission as a clinically important outcome.
      OBJECTIVES: The aims of this study were to examine frequency, timing, and
      diagnoses of 30-day readmission following carotid revascularization; to assess
      differences in 30-day readmission between patients undergoing carotid
      endarterectomy (CEA) and carotid artery stenting (CAS); to describe hospital
      variation in risk-standardized readmission rates (RSRR); and to examine whether
      hospital variation in the choice of procedure (CEA vs. CAS) is associated with
      differences in RSRRs. METHODS: We used Medicare fee-for-service administrative
      claims data to identify acute care hospitalizations for CEA and CAS from 2009 to
      2011. We calculated crude 30-day all-cause hospital readmissions following
      carotid revascularization. To assess differences in readmission after CAS
      compared with CEA, we used Kaplan-Meier survival curves and fitted mixed-effects
      logistic regression. We estimated hospital RSRRs using hierarchical generalized
      logistic regression. We stratified hospitals into 5 groups by their proportional
      CAS use and compared hospital group median RSRRs. RESULTS: Of 180,059
      revascularizations from 2,287 hospitals, CEA and CAS were performed in 81.5% and
      18.5% of cases, respectively. The unadjusted 30-day readmission rate following
      carotid revascularization was 9.6%. Readmission risk after CAS was greater than
      that after CEA. There was modest hospital-level variation in 30-day RSRRs
      (median: 9.5%; range 7.5% to 12.5%). Variation in proportional use of CAS was not
      associated with differences in hospital RSRR (range of median RSRR across
      hospital groups 9.49% to 9.55%; p = 0.771). CONCLUSIONS: Almost 10% of Medicare
      patients undergoing carotid revascularization were readmitted within 30 days of
      discharge. Compared with CEA, CAS was associated with a greater readmission risk.
      However, hospitals' RSRR did not differ by their proportional CAS use.

PMID- 25857906
TI  - Association of spontaneous bleeding and myocardial infarction with long-term
      mortality after percutaneous coronary intervention.
AB  - BACKGROUND: Platelet inhibition after percutaneous coronary intervention (PCI)
      reduces the risk of myocardial infarction (MI) but increases the risk of
      bleeding. MIs and bleeds during the index hospitalization for PCI are known to
      negatively affect long-term outcomes. The impact of spontaneous bleeding
      occurring after discharge on long-term mortality is unknown. OBJECTIVES: This
      study sought to examine, in a real-world cohort, the association between
      spontaneous major bleeding or MI after PCI and long-term mortality. METHODS: We
      conducted a retrospective cohort study of patients >=30 years of age who
      underwent a PCI between 1996 and 2008 in an integrated healthcare delivery
      system. We used extended Cox regression to examine the associations of
      spontaneous bleeding and MI with all-cause mortality, after adjustment for time
      updated demographics, comorbidities, periprocedural events, and longitudinal
      medication exposure. RESULTS: Among 32,906 patients who had a PCI and survived
      the index hospitalization, 530 had bleeds and 991 had MIs between 7 and 365 days
      post-discharge. There were 4,048 deaths over a mean follow-up of 4.42 years. The
      crude annual death rate after a spontaneous bleed (9.5%) or MI (7.6%) was higher
      than among patients who experienced neither event (2.6%). Bleeding was associated
      with an increased rate of death (adjusted hazard ratio [HR]: 1.61, 95% confidence
      interval [CI]: 1.30 to 2.00), similar to that after an MI (HR: 1.91; 95% CI: 1.62
      to 2.25). The association of bleeding with death remained significant after
      additional adjustment for the longitudinal use of antiplatelet agents.
      CONCLUSIONS: Spontaneous bleeding after a PCI was independently associated with
      higher long-term mortality, and conveyed a risk comparable to that of an MI
      during follow-up. This tradeoff between efficacy and safety bolsters the argument
      for personalizing antiplatelet therapy after PCI on the basis of the patient's
      long-term risk of both thrombotic and bleeding events.

PMID- 25857907
TI  - The conundrum of reducing ischemic and bleeding events after PCI.

PMID- 25857909
TI  - Of mice and men: the best laid scheme?

PMID- 25857908
TI  - Mechanisms of bone marrow-derived cell therapy in ischemic cardiomyopathy with
      left ventricular assist device bridge to transplant.
AB  - BACKGROUND: Clinical trials report improvements in function and perfusion with
      direct injection of bone marrow cells into the hearts of patients with ischemic
      cardiomyopathy. Preclinical data suggest these cells improve vascular density,
      which would be expected to decrease fibrosis and inflammation. OBJECTIVES: The
      goal of this study was to test the hypothesis that bone marrow stem cells (CD34+)
      will improve histological measurements of vascularity, fibrosis, and inflammation
      in human subjects undergoing left ventricular assist device (LVAD) placement as a
      bridge to cardiac transplantation. METHODS: Subjects with ischemic cardiomyopathy
      who were scheduled for placement of an LVAD as a bridge to transplantation
      underwent bone marrow aspiration the day before surgery; the bone marrow was
      processed into cell fractions (bone marrow mononuclear cells, CD34+, and CD34-).
      At LVAD implantation, all fractions and a saline control were injected
      epicardially into predetermined areas and each injection site marked. At the time
      of transplantation, injected areas were collected. Data were analyzed by paired
      Student t test comparing the effect of cell fractions injected within each
      subject. RESULTS: Six subjects completed the study. There were no statistically
      significant differences in complications with the procedure versus control
      subjects. Histological analysis indicated that myocardium injected with CD34+
      cells had decreased density of endothelial cells compared to saline-injected
      myocardium. There were no significant differences in fibrosis or inflammation
      between groups; however, density of activated fibroblasts was decreased in both
      CD34+ and CD34- injected areas. CONCLUSIONS: Tissue analysis does not support the
      hypothesis that bone marrow-derived CD34+ cells promote increased vascular tissue
      in humans with ischemic cardiomyopathy via direct injection.

PMID- 25857910
TI  - Exercise triggers ARVC phenotype in mice expressing a disease-causing mutated
      version of human plakophilin-2.
AB  - BACKGROUND: Exercise has been proposed as a trigger for arrhythmogenic right
      ventricular cardiomyopathy (ARVC) phenotype manifestation; however, research is
      hampered by the limited availability of animal models in which disease-associated
      mutations can be tested. OBJECTIVES: This study evaluated the impact of exercise
      on ARVC cardiac manifestations in mice after adeno-associated virus (AAV)
      mediated gene delivery of mutant human PKP2, which encodes the desmosomal protein
      plakophilin-2. METHODS: We developed a new model of cardiac tissue-specific
      transgenic-like mice on the basis of AAV gene transfer to test the potential of a
      combination of a human PKP2 mutation and endurance training to trigger an ARVC
      like phenotype. RESULTS: Stable cardiac expression of mutant PKP2 (c.2203C>T),
      encoding the R735X mutant protein, was achieved 4 weeks after a single AAV9-R735X
      intravenous injection. High-field cardiac magnetic resonance over a 10-month
      postinfection follow-up did not detect an overt right ventricular (RV) phenotype
      in nonexercised (sedentary) mice. In contrast, endurance exercise training
      (initiated 2 weeks after AAV9-R735X injection) resulted in clear RV dysfunction
      that resembled the ARVC phenotype (impaired global RV systolic function and RV
      regional wall motion abnormalities on cardiac magnetic resonance). At the
      histological level, RV samples from endurance-trained R735X-infected mice
      displayed connexin 43 delocalization at intercardiomyocyte gap junctions, a
      change not observed in sedentary mice. CONCLUSIONS: The introduction of the PKP2
      R735X mutation into mice resulted in an exercise-dependent ARVC phenotype. The
      R735X mutation appears to function as a dominant-negative variant. This novel
      system for AAV-mediated introduction of a mutation into wild-type mice has broad
      potential for study of the implication of diverse mutations in complex
      cardiomyopathies.

PMID- 25857911
TI  - Further evidence of harm from exercise in ARVD/C.

PMID- 25857912
TI  - Evolving therapies for myocardial ischemia/reperfusion injury.
AB  - The damage inflicted on the myocardium during acute myocardial infarction is the
      result of 2 processes: ischemia and subsequent reperfusion (ischemia/reperfusion
      injury). During the last 3 decades, therapies to reduce ischemic injury (mainly
      reperfusion strategies) have been widely incorporated into clinical practice. The
      remarkable reduction in death rates achieved with these therapies has resulted in
      a shift in emphasis from efforts to reduce mortality to a focus on tackling the
      downstream consequence of survival: post-infarction heart failure. Infarct size
      is the main determinant of long-term mortality and chronic heart failure, and
      thus, the possibility of limiting the extent of necrosis during an ST-segment
      elevation myocardial infarction is of great individual and socioeconomic value.
      After the great success of therapies to reduce ischemic injury, the time has come
      to focus efforts on therapies to reduce reperfusion injury, but in the recent few
      years, few interventions have successfully passed the proof-of-concept stage. In
      this review, we examine the past, present, and future therapies to reduce
      ischemia/reperfusion injury.

PMID- 25857913
TI  - A call for an evidence-based approach to the Heart Team for patients with severe
      aortic stenosis.
AB  - Application of a Heart Team approach is now a central concept in the care of
      patients with severe aortic stenosis. It has Class I recommendations from
      American and European professional societies and is required for reimbursement
      for transcatheter aortic valve replacement in the United States. The rationale
      for changing traditional practice models is to improve patient selection,
      procedural planning, and management of patients at high or prohibitive surgical
      risk, thus improving outcomes. Although the concept is intuitive, a clear
      definition of the Heart Team, and data supporting its effectiveness, are lacking.
      Other specialties, including oncology, provide a precedent for investigation of
      the use of a multidisciplinary team and its impact on patient care. We highlight
      the need for clear definitions and shared metrics to advance our understanding of
      an optimal Heart Team approach, focusing on patient, clinician, and health system
      outcomes. 

PMID- 25857914
TI  - Wherein lies the balance between caring and detachment?

PMID- 25857915
TI  - Spontaneous normalization of valve function after failed fibrinolytic therapy for
      left-sided prosthetic valve thrombosis.

PMID- 25857916
TI  - Atrial fibrillation ablation in patients with hypertrophic cardiomyopathy: long
      term outcomes and clinical predictors.

PMID- 25857917
TI  - Platelets interplay between pneumonia and cardiovascular events: establishing a
      link?

PMID- 25857918
TI  - Platelet activation and myocardial infarction in patients with pneumonia: are
      statins the answer?

PMID- 25857919
TI  - Reply: platelets interplay between pneumonia and cardiovascular events:
      establishing a link?

PMID- 25857920
TI  - Reply: platelets interplay between pneumonia and cardiovascular events:
      establishing a link?

PMID- 25857921
TI  - Myocardial infarction in patients with pneumonia.

PMID- 25857922
TI  - Reply: myocardial infarction in patients with pneumonia.

PMID- 25857923
TI  - Platelet activation and pneumonia: is soluble p-selectin the right marker?

PMID- 25857924
TI  - Reply: platelet activation and pneumonia: is soluble p-selectin the right marker?

PMID- 25857926
TI  - Characterization of the Major Odor-Active Compounds in the Leaves of the Curry
      Tree Bergera koenigii L. by Aroma Extract Dilution Analysis.
AB  - Curry leaves are a popular seasoning herb with a pronounced sulfury and burnt
      odor, the molecular background of which was yet unclear. Application of an aroma
      extract dilution analysis to the volatile fraction of curry leaves isolated by
      solvent extraction and solvent-assisted flavor evaporation afforded 23 odor
      active compounds with flavor dilution (FD) factors ranging from 1 to 8192. On the
      basis of the comparison of their retention indices, mass spectra, and odor
      properties with data of reference compounds, the structures of 22 odorants could
      be assigned, 15 of which had not been reported in curry leaves before. Odorants
      with high FD factors included 1-phenylethanethiol (FD factor 8192), linalool
      (4096), alpha-pinene (2048), 1,8-cineole (1024), (3Z)-hex-3-enal (256), 3
      (methylsulfanyl)propanal (128), myrcene (64), (3Z)-hex-3-en-1-ol (32), and
      (2E,6Z)-nona-2,6-dienal (32). The unique sulfury and burnt odor exhibited by 1
      phenylethanethiol in combination with its high FD factor suggested that it
      constitutes the character impact compound of fresh curry leaf aroma. 

PMID- 25857927
TI  - Thiolate versus Selenolate: Structure, Stability, and Charge Transfer Properties.
AB  - Selenolate is considered as an alternative to thiolate to serve as a headgroup
      mediating the formation of self-assembled monolayers (SAMs) on coinage metal
      substrates. There are, however, ongoing vivid discussions regarding the
      advantages and disadvantages of these anchor groups, regarding, in particular,
      the energetics of the headgroup-substrate interface and their efficiency in terms
      of charge transport/transfer. Here we introduce a well-defined model system of 6
      cyanonaphthalene-2-thiolate and -selenolate SAMs on Au(111) to resolve these
      controversies. The exact structural arrangements in both types of SAMs are
      somewhat different, suggesting a better SAM-building ability in the case of
      selenolates. At the same time, both types of SAMs have similar packing densities
      and molecular orientations. This permitted reliable competitive exchange and ion
      beam-induced desorption experiments which provided unequivocal evidence for a
      stronger bonding of selenolates to the substrate as compared to the thiolates.
      Regardless of this difference, the dynamic charge transfer properties of the
      thiolate- and selenolate-based adsorbates were found to be nearly identical, as
      determined by the core-hole-clock approach, which is explained by a
      redistribution of electron density along the molecular framework, compensating
      the difference in the substrate-headgroup bond strength. 

PMID- 25857925
TI  - MicroRNA29a regulates IL-33-mediated tissue remodelling in tendon disease.
AB  - MicroRNA (miRNA) has the potential for cross-regulation and functional
      integration of discrete biological processes during complex physiological events.
      Utilizing the common human condition tendinopathy as a model system to explore
      the cross-regulation of immediate inflammation and matrix synthesis by miRNA we
      observed that elevated IL-33 expression is a characteristic of early
      tendinopathy. Using in vitro tenocyte cultures and in vivo models of tendon
      damage, we demonstrate that such IL-33 expression plays a pivotal role in the
      transition from type 1 to type 3 collagen (Col3) synthesis and thus early tendon
      remodelling. Both IL-33 effector function, via its decoy receptor sST2, and Col3
      synthesis are regulated by miRNA29a. Downregulation of miRNA29a in human
      tenocytes is sufficient to induce an increase in Col3 expression. These data
      provide a molecular mechanism of miRNA-mediated integration of the early
      pathophysiologic events that facilitate tissue remodelling in human tendon after
      injury. 

PMID- 25857928
TI  - Improving confidence in environmental DNA species detection.
AB  - Will we catch fish today? Our grandfathers' responses were usually something
      along the lines of, 'Probably. I've caught them here before'. One of the
      foundations of ecology is identifying which species are present, and where. This
      informs our understanding of species richness patterns, spread of invasive
      species, and loss of threatened and endangered species due to environmental
      change. However, our understanding is often lacking, particularly in aquatic
      environments where biodiversity remains hidden below the water's surface. The
      emerging field of metagenetic species surveillance is aiding our ability to
      rapidly determine which aquatic species are present, and where. In this issue of
      Molecular Ecology Resources, Ficetola et al. () provide a framework for
      metagenetic environmental DNA surveillance to foster the confidence of our
      grandfathers' fishing prowess by more rigorously evaluating the replication
      levels necessary to quantify detection errors and ultimately improving our
      confidence in aquatic species presence. 

PMID- 25857929
TI  - Genomic resources notes accepted 1 December 2014 - 31 January 2015.
AB  - This article documents the public availability of (i) transcriptome sequence data
      and assembly for the rostrum dace (Leuciscus burdigalensis) naturally infected by
      a copepod ectoparasite (Tracheliastes polycolpus) and (ii) SNPs identified and
      validated from RAD sequencing for the Ugandan red colobus (Procolobus
      rufomitratus tephrosceles) using RAD sequencing. 

PMID- 25857930
TI  - The face of female dominance: Women with dominant faces have lower cortisol.
AB  - The human face displays a wealth of information, including information about
      dominance and fecundity. Dominance and fecundity are also associated with lower
      concentrations of the stress hormone cortisol, suggesting that cortisol may
      negatively predict facial dominance and attractiveness. We digitally photographed
      61 women's faces, had these images rated by men and women for dominance,
      attractiveness, and femininity, and explored relationships between these
      perceptions and women's salivary cortisol concentrations. In a first study, we
      found that women with more dominant-appearing, but not more attractive, faces had
      lower cortisol levels. These associations were not due to age, ethnicity, time
      since waking, testosterone, or its interaction with cortisol. In a second study,
      composite images of women with low cortisol were perceived as more dominant than
      those of women with high cortisol significantly more often than chance by two
      samples of viewers, with a similar but non-significant trend in a third sample.
      However, data on perceptions of attractiveness were mixed; low-cortisol images
      were viewed as more attractive by two samples of US viewers and as less
      attractive by a sample of Mexican viewers. Our results suggest that having a more
      dominant-appearing face may be associated with lower stress and hence lower
      cortisol in women, and provide further evidence regarding the information content
      of the human face. 

PMID- 25857932
TI  - Reconstructing a Carboniferous inferred coral-alcyonarian association using a
      biomineralogical approach.
AB  - The taxonomic assignation and ecological implications of the genus Syringoalcyon
      Termier & Termier, 1945 have been a palaeontological problem for a long time.
      Carboniferous material from Morocco and Spain has been studied using a
      biomineralogical approach by means of petrographic microscopy, SEM, AFM, EMPA and
      CIP microscopy analysis. Detailed morphological, structural, chemical composition
      and crystallographic data enable a deeper understanding of the nature of
      Syringoalcyon. The coral walls and the so-called epithecal scales exhibit
      conspicuous differences in microstructure (lamellae and holacanthine fibres in
      the coral vs. single crystal in scales), nanostructure (pill-shaped vs. granule
      shaped nanocrystals), composition (LMC vs. HMC) and crystallographic orientation.
      The results of these analyses imply that Syringoalcyon is an association between
      the tabulate coral Syringopora and an epibiont. They also suggest that the
      epibiont was an alcyonarian (a rare occurrence in the fossil record) that was
      attached to the syringoporoid. This work highlights the utility of the
      biomineralizational approaches for solving palaeontological problems, such as
      systematic affinities, and for advancing knowledge of the evolution of
      biocrystallization processes. 

PMID- 25857931
TI  - Population genomic evidence for adaptive differentiation in Baltic Sea three
      spined sticklebacks.
AB  - BACKGROUND: The degree of genetic differentiation among populations experiencing
      high levels of gene flow is expected to be low for neutral genomic sites, but
      substantial divergence can occur in sites subject to directional selection.
      Studies of highly mobile marine fish populations provide an opportunity to
      investigate this kind of heterogeneous genomic differentiation, but most studies
      to this effect have focused on a relatively low number of genetic markers and/or
      few populations. Hence, the patterns and extent of genomic divergence in high
      gene flow marine fish populations remain poorly understood. RESULTS: We here
      investigated genome-wide patterns of genetic variability and differentiation in
      10 marine populations of three-spined stickleback (Gasterosteus aculeatus)
      distributed across a steep salinity and temperature gradient in the Baltic Sea,
      by utilizing > 30,000 single nucleotide polymorphisms obtained with a pooled RAD
      seq approach. We found that genetic diversity and differentiation varied widely
      across the genome, and identified numerous fairly narrow genomic regions
      exhibiting signatures of both divergent and balancing selection. Evidence was
      uncovered for substantial genetic differentiation associated with both salinity
      and temperature gradients, and many candidate genes associated with local
      adaptation in the Baltic Sea were identified. CONCLUSIONS: The patterns of
      genetic diversity and differentiation, as well as candidate genes associated with
      adaptation in Baltic Sea sticklebacks were similar to those observed in earlier
      comparisons between marine and freshwater populations, suggesting that similar
      processes may be driving adaptation to brackish and freshwater environments.
      Taken together, our results provide strong evidence for heterogenic genomic
      divergence driven by local adaptation in the face of gene flow along an
      environmental gradient in the post-glacially formed Baltic Sea.

PMID- 25857933
TI  - Brain activation during processing of angry facial expressions in patients with
      alcohol dependency.
AB  - BACKGROUND: Alcoholism is associated with abnormal anger processing. The purpose
      of this study was to investigate brain regions involved in the evaluation of
      angry facial expressions in patients with alcohol dependency. METHODS: Brain
      blood-oxygenation-level-dependent (BOLD) responses to angry faces were measured
      and compared between patients with alcohol dependency and controls. RESULTS:
      During intensity ratings of angry faces, significant differences in BOLD were
      observed between patients with alcohol dependency and controls. That is, patients
      who were alcohol-dependent showed significantly greater activation in several
      brain regions, including the dorsal anterior cingulate cortex (dACC) and medial
      prefrontal cortex (MPFC). CONCLUSIONS: Following exposure to angry faces,
      abnormalities in dACC and MPFC activation in patients with alcohol dependency
      indicated possible inefficiencies or hypersensitivities in social cognitive
      processing.

PMID- 25857934
TI  - Toll-like receptor 1 variations influence susceptibility and immune response to
      Mycobacterium tuberculosis.
AB  - BACKGROUND: Tuberculosis (TB), a disease caused by Mycobacterium tuberculosis
      (MTB) infection, is still a global public health problem. TB susceptibility
      varies greatly in infected individuals, and mycobacterial recognition by the
      innate immune system likely affects disease course and outcome. This research
      describes a single nucleotide polymorphism in the Toll-like receptor (TLR) 1 gene
      that functionally alters the innate immune response to MTB and is associated with
      TB susceptibility in India. METHODS: 206 TB patients and 239 healthy controls
      from Hyderabad, India were analyzed for SNPs in the TLR1 and TLR2 genes, which
      were subsequently correlated to TB susceptibility. To test individual responses
      to MTB lysates, we stimulated PBMCs from genotyped healthy German individuals, as
      well as HEK cells transfected with TLR1/2 variants. TNF production and NF-kB
      activation were assessed respectively. RESULTS: Cohort analysis associated the
      TLR1-248N SNP (RS4833095) with TB protection. TLR1-248N expressing PBMCs from
      healthy controls exhibited an increased TNF response to MTB lysates. In addition
      to this, functional studies using HEK cell lines transfected with TLR1-248N and
      stimulated with MTB showed an increased NF-kB activation. CONCLUSION: SNP TLR1
      248N is associated with TB protection in an Indian population and exhibits an
      increased immune response to MTB lysate in vitro.

PMID- 25857936
TI  - The Early Mediaeval manorial estate of Gars/Thunau, Lower Austria: An enclave of
      endemic tuberculosis?
AB  - In recent decades, an increasing number of studies have aimed to shed light on
      the origin and spread of tuberculosis in past human populations. Here we present
      the results of a systematic palaeodemographic and palaeopathological survey of
      the Early Mediaeval population of Gars/Thunau (Lower Austria), which - at this
      stage - includes 373 individuals recovered at two archaeological sub-sites: a
      fortified settlement (including a necropolis) at the top of a hill - probably
      reserved for social and military elites; and a large riverine settlement at the
      foot of the hill, a so-called 'suburbium', where burials and an area of
      'industrial' character were discovered. We recorded a great number of
      pathological alterations and a variety of 'classical' features of tuberculosis,
      such as vertebral destructions (Pott's disease) and joint destructions, and other
      pathological (unspecific) features probably linked with Mycobacterium
      tuberculosis infection (e.g. new bone formation at the inner surface of the ribs,
      endocranial alterations in the form of 'pits', and new bone formation at the
      cranial base). We hypothesize that the two contemporaneous (~900-1000 AD)
      populations of Gars/Thunau differed not only in their social
      affiliation/condition, but also in the type and frequencies of their population
      density-related infectious diseases (in particular tuberculosis). Moreover, we
      investigated the molecular genetic evidence of the causative organism in a few
      selected immatures exhibiting pathological changes at the inner wall of the
      cranium and discuss these findings in regard to the macroscopic features
      observed. Finally, we analysed carbon and nitrogen stable isotopes of both
      populations and strontium isotope ratios of the hill-top inhabitants in order to
      reconstruct certain aspects of diet and mobility to test our hypothesis
      concerning the specific social and/or military character of the site.

PMID- 25857937
TI  - Tuberculosis in Late Neolithic-Early Copper Age human skeletal remains from
      Hungary.
AB  - Alsonyek-Bataszek in Southern Hungary is one of the largest late Neolithic
      settlements and cemeteries excavated in Central Europe. In total, 2359 burials
      from the Late Neolithic - Early Copper Age Lengyel culture were found between
      2006 and 2009 [1]. Anthropological investigations previously carried out on
      individuals from this site revealed an interesting paleopathological case of
      tuberculosis in the form of Pott's disease dated to the early 5(th) millennium
      BC. In this study, selected specimens from this osteoarcheological series were
      subjected to paleomicrobiological analysis to establish the presence of MTBC
      bacteria. As all individuals showing clear osteological signs of TB infection
      belonged to a single grave group, 38 individuals from this grave group were
      analysed. The sample included the case of Pott's disease as well as individuals
      both with and without osseous TB manifestations. The detection of TB DNA in the
      individual with Pott's disease provided further evidence for the occurrence of TB
      in Neolithic populations of Europe. Moreover, our molecular analysis indicated
      that several other individuals of the same grave group were also infected with
      TB, opening the possibility for further analyses of this unique Neolithic
      skeletal series.

PMID- 25857935
TI  - Identification of novel Mycobacterium tuberculosis CD4 T-cell antigens via high
      throughput proteome screening.
AB  - Elicitation of CD4 IFN-gamma T cell responses to Mycobacterium tuberculosis (MTB)
      is a rational vaccine strategy to prevent clinical tuberculosis. Diagnosis of MTB
      infection is based on T-cell immune memory to MTB antigens. The MTB proteome
      contains over four thousand open reading frames (ORFs). We conducted a pilot
      antigen identification study using 164 MTB proteins and MTB-specific T-cells
      expanded in vitro from 12 persons with latent MTB infection. Enrichment of MTB
      reactive T-cells from PBMC used cell sorting or an alternate system compatible
      with limited resources. MTB proteins were used as single antigens or
      combinatorial matrices in proliferation and cytokine secretion readouts. Overall,
      our study found that 44 MTB proteins were antigenic, including 27 not previously
      characterized as CD4 T-cell antigens. Antigen truncation, peptide, NTM homology,
      and HLA class II tetramer studies confirmed malate synthase G (encoded by gene
      Rv1837) as a CD4 T-cell antigen. This simple, scalable system has potential
      utility for the identification of candidate MTB vaccine and biomarker antigens.

PMID- 25857938
TI  - Operative Treatment for Fourth Curly Toe Deformity in Adults.
AB  - BACKGROUND: Curly toe deformity, a relatively common condition, occurs because of
      contracture of the flexor digitorum longus and flexor digitorum brevis. Numerous
      operative techniques have been introduced for treatment. However, there are no
      reports on fixed, longstanding deformity in adults. METHODS: Data on 32 toes in
      24 consecutive patients treated from 2003 to 2013 who underwent dorsolateral
      closing wedge-shaped resection arthroplasty for fourth curly toe deformity with a
      minimum 1-year follow-up were reviewed retrospectively. The mean follow-up period
      was 49 months. All patients presented preoperatively with a fixed deformity,
      underriding the adjacent toe. Combined surgeries were performed in 17 cases.
      RESULTS: Of 32 toes, fixed deformity presented more frequently at the proximal
      interphalangeal (PIP) joint, and resection at the PIP joint level was performed
      in 19 cases as opposed to 13 at the distal interphalangeal joint. The mean
      corrections of varus inclination and shortening were 31 +/- 16 degrees and 3.1 +/
      2.1 mm, respectively. American Orthopaedic Foot & Ankle Society scores
      significantly improved from 50 +/- 2 preoperatively to 89 +/- 8 at the final
      follow-up. There was 1 case of recurrence, floating toe deformity following pin
      tract infection in 1 case, and floating toe deformity without infection in 1
      case. CONCLUSION: We introduced dorsolateral closing wedge-shaped resection
      arthroplasty as a simple, effective, and powerful option for treating fixed,
      longstanding fourth curly toe deformity in adults. LEVEL OF EVIDENCE: Level IV,
      retrospective case series.

PMID- 25857939
TI  - Randomized Controlled Trial Comparing Orthosis Augmented by Either Stretching or
      Stretching and Strengthening for Stage II Tibialis Posterior Tendon Dysfunction.
AB  - BACKGROUND: The value of strengthening and stretching exercises combined with
      orthosis treatment in a home-based program has not been evaluated. The purpose of
      this study was to compare the effects of augmenting orthosis treatment with
      either stretching or a combination of stretching and strengthening in
      participants with stage II tibialis posterior tendon dysfunction (TPTD). METHODS:
      Participants included 39 patients with stage II TPTD who were recruited from a
      medical center and then randomly assigned to a strengthening or stretching
      treatment group. Excluding 3 dropouts, there were 19 participants in the
      strengthening group and 17 in the stretching group. The stretching treatment
      consisted of a prefabricated orthosis used in conjunction with stretching
      exercises. The strengthening treatment consisted of a prefabricated orthosis used
      in conjunction with the stretching and strengthening exercises. The main outcome
      measures were self-report (ie, Foot Function Index and Short Musculoskeletal
      Function Assessment) and isometric deep posterior compartment strength. Two-way
      analysis of variance was used to test for differences between groups at 6 and 12
      weeks after starting the exercise programs. RESULTS: Both groups significantly
      improved in pain and function over the 12-week trial period. The self-report
      measures showed minimal differences between the treatment groups. There were no
      differences in isometric deep posterior compartment strength. CONCLUSIONS: A
      moderate-intensity, home-based exercise program was minimally effective in
      augmenting orthosis wear alone in participants with stage II TPTD. LEVEL OF
      EVIDENCE: Level I, prospective randomized study.

PMID- 25857940
TI  - Efficacy and Accessibility of a Novel Liver Fibrosis Evaluation Program: Limited
      Abdominal Ultrasound with Concurrent Transient Elastography.
AB  - RATIONALE AND OBJECTIVES: To review sustainability and fair access related to
      setting up a centralized transient elastography (TE) program in the radiology
      department and to perform a quality assessment of a novel liver fibrosis
      evaluation program that combines TE with limited abdominal ultrasound (US).
      MATERIAL AND METHODS: As part of a quality assessment, a retrospective chart
      review was performed on 758 patients who underwent TE immediately after limited
      abdominal US of the liver over a 12-month period. The elastography results and
      sonographic findings were documented, including the number and type of lesions
      identified. In terms of fair access evaluation, the indication for TE and
      referring service was reviewed for each case. RESULTS: Most referrals were
      initiated by infectious disease (52.2% [396 of 758]) or gastroenterology (46.3%
      [351 of 758]) for patients with viral hepatitis (29.8% [226 of 758] for HBV and
      52.2% [396 of 758] for HCV) and nonalcoholic steatohepatitis (11.9% [90 of 758]).
      Only 3.2% (24 of 758) of indications were outside the usual indications for which
      standardized values of TE were available. Most studies demonstrated minimal
      fibrosis (66.6% [510 of 766] <=F1) or more advanced fibrosis (21.1% [162 of 766]
      >=F3). Liver nodularity was observed in 63 cases, correlating to F2 fibrosis and
      above in 81.0% (51 of 63). US screening detected five new cases of hepatocellular
      carcinoma (HCC). CONCLUSIONS: This unique program allows fair access and ensures
      that referrals are requested for appropriate indications. Concurrent US confers
      many advantages including proper TE probe placement to optimize measurement
      success, characterization of sonographic features that correlate with advanced
      fibrosis, and provides an opportunity to screen for HCC, in a population which
      may not otherwise have access to standardized screening.

PMID- 25857942
TI  - The synthesis and evaluation of sesamol and benzodioxane derivatives as
      inhibitors of monoamine oxidase.
AB  - In the present study, series of eight sesamol (1,3-benzodioxol-5-ol) and eight
      benzodioxane (2,3-dihydro-1,4-benzodioxine) derivatives were synthesised and
      evaluated as inhibitors of recombinant human monoamine oxidase (MAO) A and B. The
      sesamol and benzodioxane derivatives are structurally related to series of
      phthalide derivatives, which have previously been found to act as potent
      reversible MAO inhibitors. The results document that the benzodioxane
      derivatives, in particular, are potent MAO-B inhibitors with IC50 values ranging
      from 0.045 to 0.947 MUM. IC50 values for the inhibition of MAO-B by the
      homologous series of sesamol derivatives ranged from 0.164 to 7.29 MUM. All
      compounds evaluated are selective for the MAO-B isoform, with IC50 values for the
      inhibition of MAO-A ranging from 13.2 to >100 MUM. It is further shown that for
      the most potent MAO-B inhibitor, 6-[(3-bromophenyl)methoxy]-2,3-dihydro-1,4
      benzodioxine, inhibition is almost completely reversed by dialysis of enzyme
      inhibitor mixtures. It may be concluded that benzodioxane derivatives are
      promising leads for the design of selective MAO-B inhibitors for the treatment of
      Parkinson's disease.

PMID- 25857941
TI  - BMS-871: a novel orally active pan-Notch inhibitor as an anticancer agent.
AB  - This Letter describes synthesis, SAR, and biological activity of (2-oxo-1,4
      benzodiazepin-3-yl)-succinamides as inhibitors of gamma-secretase mediated
      signaling of Notch receptors. Optimization of this series led to the
      identification of BMS-871 (compound 30) which displayed robust in vivo efficacy
      in Notch-dependent leukemia and solid tumor xenograft models. 

PMID- 25857943
TI  - Integration of antibody by surface functionalization of graphite-encapsulated
      magnetic beads using ammonia gas plasma technology for capturing influenza A
      virus.
AB  - Antibody-integrated magnetic beads have been functionalized for influenza A virus
      capture. First, ammonia plasma produced by a radio frequency power source was
      reacted with the surface of graphite-encapsulated magnetic beads to introduce
      amino groups. Anti-influenza A virus hemagglutinin antibody was then anchored by
      its surface sulfide groups to the amino groups on the beads via N-succinimidyl 3
      (2-pyridyldithio) propionate. After incubation with influenza A virus, adsorption
      of the virus to the beads was confirmed by immunochromatography, polymerase chain
      reaction (PCR), enzyme-linked immunosorbent assay (ELISA), and inoculation of
      chicken embryonated eggs, indicating that virus infectivity is maintained and
      that the proposed method is useful for the enhanced detection and isolation of
      influenza A virus. 

PMID- 25857944
TI  - Labeling and preliminary in vivo evaluation of the 5-HT(7) receptor selective
      agonist [(11)C]E-55888.
AB  - E-55888 has been identified as a selective serotonin 7 (5-HT7) receptor agonist.
      In this study, we describe the synthesis, radiolabeling and in vivo evaluation of
      [(11)C]E-55888 as a radioligand for positron emission tomography (PET) imaging.
      [(11)C]E-55888 was obtained by N-methylation of an appropriate precursor using
      [(11)C]MeOTf in acetone at 60  degrees C giving isolated quantities in the range
      of 1.7-2.4 GBq. Studies in Danish Landrace pigs demonstrated that [(11)C]E-55888
      has good brain uptake, however, the distribution in the brain tissue was
      dominated by non-specific binding, as binding could neither be displaced by the
      structurally different 5-HT7 receptor ligand SB-269970 nor by self-block with
      unlabeled E-55888. Based on these data, [(11)C]E-55888 does not show promise as a
      PET radioligand for imaging the 5-HT7 receptor in vivo.

PMID- 25857945
TI  - Hippocampal BDNF signaling restored with chronic asiaticoside treatment in
      depression-like mice.
AB  - Brain-derived neurotrophic factor (BDNF) plays a key role in the regulation of
      depression in the brain. Recently, increasing studies have focused on the
      antidepressant-like mechanism of BDNF and its downstream signaling pathway. A
      previous study has shown that asiaticoside produced an antidepressant-like action
      in the mouse tail suspension test and forced swimming test. However, the
      neurotrophic mechanism that is affected by asiaticoside is unclear. Our present
      study aimed to verify whether asiaticoside produces an antidepressant-like effect
      through the activation of BDNF signaling in chronic unpredictable mild stress
      (CUMS). The results showed that mice treated with asiaticoside for four weeks
      reversed the decreased sucrose preference and increased immobility time that was
      observed in CUMS mice. In addition, we found that asiaticoside up-regulated BDNF,
      PSD-95 and synapsin I expression only in the hippocampus but not in the frontal
      cortex in both non-stressed and CUMS mice. However, K252a, an inhibitor of BDNF
      receptor tropomyosin-related kinase receptor B (TrkB), completely abolished the
      antidepressant-like effect of asiaticoside. Moreover, the expression of
      hippocampal BDNF, PSD-95 and synapsin I that had increased with asiaticoside also
      declined with K252a pretreatment. In conclusion, our study implies that it is
      possible that asiaticoside exerts its antidepressant-like action by activating
      BDNF signaling in the hippocampus.

PMID- 25857947
TI  - Yokukansan normalizes glucocorticoid receptor protein expression in
      oligodendrocytes of the corpus callosum by regulating microRNA-124a expression
      after stress exposure.
AB  - Stressful events are known to down-regulate expression levels of glucocorticoid
      receptors (GRs) in the brain. Recently, we reported that stressed mice with
      elevated plasma levels of corticosterone exhibit morphological changes in the
      oligodendrocytes of nerve fiber bundles, such as those in the corpus callosum.
      However, little is known about the molecular mechanism of GR expression
      regulation in oligodendrocytes after stress exposure. A previous report has
      suggested that GR protein levels might be regulated by microRNA (miR)-18 and/or 
      124a in the brain. In this study, we aimed to elucidate the GR regulation
      mechanism in oligodendrocytes and evaluate the effects of yokukansan (YKS), a
      Kampo medicine, on GR protein regulation. Acute exposure to stress increased
      plasma corticosterone levels, decreased GR protein expression, and increased miR
      124a expression in the corpus callosum of adult male mice, though the GR mRNA and
      miR-18 expression levels were not significant changes. YKS normalized the stress
      induced changes in the plasma corticosterone, GR protein, and miR124a expression
      levels. An oligodendrocyte primary culture study also showed that YKS down
      regulated miR-124a, but not miR-18, expression levels in dexamethasone-treated
      cells. These results suggest that the down-regulation of miR124a expression might
      be involved in the normalization of stress-induced decreases in GR protein in
      oligodendrocytes by YKS. This effect may imply the molecular mechanisms
      underlying the ameliorative effects of YKS on psychological symptoms and stress
      related behaviors.

PMID- 25857946
TI  - In vivo evidence for neuroplasticity in older adults.
AB  - Neuroplasticity can be conceptualized as an intrinsic property of the brain that
      enables modification of function and structure in response to environmental
      demands. Neuroplastic strengthening of synapses is believed to serve as a
      critical mechanism underlying learning, memory, and other cognitive functions. Ex
      vivo work investigating neuroplasticity has been done on hippocampal slices using
      high frequency stimulation. However, in vivo neuroplasticity in humans has been
      difficult to demonstrate. Recently, a long-term potentiation-like phenomenon, a
      form of neuroplastic change, was identified in young adults by differences in
      visual evoked potentials (VEPs) that were measured before and after tetanic
      visual stimulation (TVS). The current study investigated whether neuroplastic
      changes in the visual pathway can persist in older adults. Seventeen healthy
      subjects, 65 years and older, were recruited from the community. Subjects had a
      mean age of 77.4 years, mean education of 17 years, mean MMSE of 29.1, and
      demonstrated normal performance on neuropsychological tests. 1Hz checkerboard
      stimulation, presented randomly to the right or left visual hemi-field, was
      followed by 2min of 9Hz stimulation (TVS) to one hemi-field. After 2min of rest,
      1Hz stimulation was repeated. Temporospatial principal component analysis was
      used to identify the N1b component of the VEPs, at lateral occipital locations,
      in response to 1Hz stimulation pre- and post-TVS. Results showed that the
      amplitude of factors representing the early and late N1b component was
      substantially larger after tetanic stimulation. These findings indicate that high
      frequency visual stimulation can enhance the N1b in cognitively high functioning
      old adults, suggesting that neuroplastic changes in visual pathways can continue
      into late life. Future studies are needed to determine the extent to which this
      marker of neuroplasticity is sustained over a longer period of time, and is
      influenced by age, cognitive status, and neurodegenerative disease.

PMID- 25857948
TI  - Standard dosing of amikacin and gentamicin in critically ill patients results in
      variable and subtherapeutic concentrations.
AB  - Low peak plasma concentrations (Cmax) of amikacin and gentamicin are reported in
      intensive care unit (ICU) patients after administration of the first dose. The
      present study aimed to describe the proportion of ICU patients in whom an
      adequate Cmax was achieved throughout the course of therapy. Septic ICU patients
      with an indication for intravenous amikacin or gentamicin were eligible for
      inclusion in this single-centre observational study. The first and subsequent
      doses and the corresponding Cmax values were recorded. The target Cmax was
      >=60mg/L for amikacin and >=30mg/L for gentamicin. Amikacin and gentamicin plasma
      concentrations were available in 66 and 24 patients, respectively (59+/-17 years;
      79+/-19kg; height 169+/-12cm; SAPS II score 46+/-19). Pulmonary, abdominal and
      urinary tract infections were diagnosed in 64 patients. Culture-positive
      infection was confirmed in 65 patients (72%). A target first Cmax was achieved in
      17/90 patients (19%). For amikacin, the target Cmax was achieved in 16/66
      patients (24%) after the initial dose. In the 50 remaining patients, a change in
      dosing was performed in 14 patients, leading adequate peak plasma level in 2
      patients. For gentamicin, the targeted Cmax was achieved in only 1/24 patient
      (4%) after the initial dose and was never achieved after the third dose. In
      conclusion, standard dosing of amikacin or gentamicin led to adequate Cmax in
      only 19% of patients. Subtherapeutic Cmax were not significantly corrected after
      subsequent doses. 

PMID- 25857949
TI  - Emerging broad-spectrum resistance in Pseudomonas aeruginosa and Acinetobacter
      baumannii: Mechanisms and epidemiology.
AB  - Multidrug resistance is quite common among non-fermenting Gram-negative rods, in
      particular among clinically relevant species including Pseudomonas aeruginosa and
      Acinetobacter baumannii. These bacterial species, which are mainly nosocomial
      pathogens, possess a diversity of resistance mechanisms that may lead to
      multidrug or even pandrug resistance. Extended-spectrum beta-lactamases (ESBLs)
      conferring resistance to broad-spectrum cephalosporins, carbapenemases conferring
      resistance to carbapenems, and 16S rRNA methylases conferring resistance to all
      clinically relevant aminoglycosides are the most important causes of concern.
      Concomitant resistance to fluoroquinolones, polymyxins (colistin) and tigecycline
      may lead to pandrug resistance. The most important mechanisms of resistance in P.
      aeruginosa and A. baumannii and their most recent dissemination worldwide are
      detailed here. 

PMID- 25857950
TI  - The prevalence of malaria among HIV seropositive individuals and the impact of
      the co- infection on their hemoglobin levels.
AB  - BACKGROUND: Malaria and HIV/AIDS are the two most common infections in sub-Sahara
      Africa. There are hypotheses and study reports on the possible association
      between these two infections, hence the prevalence and outcome of their co
      infection in an endemic population will be important in defining healthcare
      strategies. A cross sectional study was carried out at the Holy Family Hospital
      in Techiman, Ghana, between November 2011 and January 2012, to determine the
      prevalence of malaria among HIV sero-positive patients and its impact on
      hemoglobin levels. METHOD: A total of 400 HIV sero-positive participants (292
      females and 108 males) aged between 1 and 73 years were randomly sampled for the
      study. A questionnaire was administered and 2 ml of venous blood samples were
      drawn for malaria parasites detection, CD4 count and haemoglobin level
      estimations. RESULTS: Malaria parasites were detected in 47 (11.75%) of the
      participants. There was no statistically significant difference between the
      malaria prevalence rate of females (12.1%) and males (10.2%) P = 0.6047. An
      overall anaemia prevalence of 67% was observed. Among participants with malaria
      the anaemia prevalence was 93.6%. The CD4 cell count of all the participants
      ranged between 3 and 1604 cells/MUl with a mean of 386.2 (+/-274.3) cells/MUl.
      Participants with malaria had CD4 cell count ranged 3 and 512 Cells/MUl with the
      mean being 186.33 (+/-133.49) Cells/MUl. Out of 377 participants (all above 15
      years) interviewed on knowledge of malaria transmission and prevention, 87.0% had
      knowledge on transmission but only 8.5% use in bed nets. CONCLUSION: It was
      revealed that almost all the patients with malaria infection were anemic.

PMID- 25857951
TI  - Failing softly: a fracture theory of highly-deformable materials.
AB  - Highly-deformable materials, from synthetic hydrogels to biological tissues, are
      becoming increasingly important from both fundamental and practical perspectives.
      Their mechanical behaviors, in particular the dynamics of crack propagation
      during failure, are not yet fully understood. Here we propose a theoretical
      framework for the dynamic fracture of highly-deformable materials, in which the
      effects of a dynamic crack are treated with respect to the nonlinearly deformed
      (pre-stressed/strained), non-cracked, state of the material. Within this
      framework, we derive analytical and semi-analytical solutions for the near-tip
      deformation fields and energy release rates of dynamic cracks propagating in
      incompressible neo-Hookean solids under biaxial and uniaxial loading. We show
      that moderately large pre-stressing has a marked effect on the stress fields
      surrounding a crack's tip. We verify these predictions by performing extensive
      experiments on the fracture of soft brittle elastomers over a range of loading
      levels and propagation velocities, showing that the newly developed framework
      offers significantly better approximations to the measurements than standard
      approaches at moderately large levels of external loadings and high propagation
      velocities. This framework should be relevant to the failure analysis of soft and
      tough, yet brittle, materials. 

PMID- 25857952
TI  - Johan Anton Waldenstrom, a versatile doctor and pioneer: Professor of medicine
      and practising surgeon.

PMID- 25857953
TI  - Physicochemical characterization of the polysaccharide from Bletilla striata:
      effect of drying method.
AB  - The polysaccharide from Bletilla striata, a traditional Chinese herbal medicine,
      was obtained by different drying techniques: vacuum-drying (BVPS) or vacuum
      freeze-drying (BFPS). The effect of drying method on the physicochemical
      properties of the B striata polysaccharide was evaluated using high size
      exclusion chromatography coupled to multiangle laser light scattering (HPSEC
      MALLS), FT-IR and UV spectroscopy, thermogravimetric analysis (TGA), differential
      scanning calorimetry (DSC), X-ray diffraction (XRD), scanning electron microscopy
      (SEM) and atomic force microscopy (AFM). The monosaccharide analysis and pH test
      revealed that the polysaccharide derived from B. striata was a neutral
      polysaccharide that is composed of glucose and mannose. The solubility and
      moisture content test's results demonstrated that BFPS was greater than BVPS. The
      number average molecular weight (Mn) and the computed average molecular weight
      (Mw) of 99.3% BFPS were 7.297*10(4)g/mol and 9.545*10(4)g/mol, respectively,
      whereas the Mn and Mw of 97.6% BVPS were 1.218*10(5)g/mol and 1.472*10(5)g/mol,
      respectively. The FT-IR and UV results indicated that drying technique has little
      effect on the structure of the polysaccharide. The thermal analysis showed that
      weight loss event was at 307.85 degrees C and 305.50 degrees C to BVPS and BFPS,
      respectively. Furthermore, the XRD confirmed that the polysaccharide was the
      amorphous nature. However, both SEM and AFM images exhibited that the drying
      technique had a significant impact on the morphology and conformation of the
      polysaccharide.

PMID- 25857954
TI  - In vitro digestibility and some physicochemical properties of starch from wild
      and cultivated amadumbe corms.
AB  - Amadumbe, commonly known as taro, is an indigenous underutilised tuber to
      Southern Africa. In this study, starch functional properties and in vitro starch
      digestibility of processed products from wild and cultivated amadumbe were
      determined. Starch extracts from both amadumbe types had similar contents of
      total starch (approx. 95%). Wild and cultivated amadumbe starch granules were
      polygonal and very small in size (2.7 +/- 0.9 MUm). Amylose content of wild
      amadumbe (20%) was about double that of cultivated (12%). By DSC, the peak
      gelatinisation temperatures of wild and cultivated amadumbe starches were 81 and
      85 degrees C, respectively. The slowly digestible starch (SDS); 20% and resistant
      starch (RS); 64% contents of wild amadumbe appeared slightly higher than those of
      cultivated. Processing amadumbe into boiled and baked products did not
      substantially affect SDS and RS contents. Estimated glycaemic index of processed
      products ranged from 40 to 44%. Thus, amadumbe, both wild and cultivated, present
      some potential in the formulation of products for diabetics and weight
      management.

PMID- 25857955
TI  - Characterization of an exopolysaccharide produced by Lactobacillus plantarum YW11
      isolated from Tibet Kefir.
AB  - An exopolysaccharide (EPS)-producing strain YW11 isolated from Tibet Kefir was
      identified as Lactobacillus plantarum, and the strain was shown to produce 90
      mgL(-1) of EPS when grown in a semi-defined medium. The molecular mass of the EPS
      was 1.1 * 10(5)Da. The EPS was composed of glucose and galactose in a molar ratio
      of 2.71:1, with possible presence of N-acetylated sugar residues in the
      polysaccharide as confirmed by NMR spectroscopy. Rheological studies showed that
      the EPS had higher viscosity in skim milk, at lower temperature, or at acidic pH.
      The viscous nature of the EPS was confirmed by observation with scanning electron
      microscopy that demonstrated a highly branched and porous structure of the
      polysaccharide. The atomic force microscopy of the EPS further revealed presence
      of many spherical lumps, facilitating binding with water in aqueous solution. The
      EPS had a higher degradation temperature (287.7 degrees C), suggesting high
      thermal stability of the EPS.

PMID- 25857957
TI  - Relationship between structure and functional properties of normal rice starches
      with different amylose contents.
AB  - The structures (morphology, molecule, and crystallinity) and functional
      properties (gelatinization, hydrolysis, and in vitro digestion) of normal rice
      starches with different amylose contents were investigated and their
      relationships were analyzed. The results showed that the morphology, granule
      size, and crystalline type did not significantly change among rice starches. The
      molecular structure (amylose content, amylopectin branch-chain content, and
      amylopectin branching degree) and crystalline structure (relative crystallinity,
      IR ratio of 1045/1022 cm(-1), lamellar peak intensity, and lamellar distance)
      significantly varied among rice starches, which resulted in different functional
      properties. The gelatinization temperature and water solubility were
      significantly positively correlated with amylose content but significantly
      negatively correlated with amylopectin short branch-chain. The swelling power,
      hydrolysis and in vitro digestion were significantly positively correlated with
      amylopectin short branch-chain, relative crystallinity, IR ratio of 1045/1022 cm(
      1), and lamellar peak intensity but significantly negatively correlated with
      amylose content and lamellar distance.

PMID- 25857956
TI  - Effect of pH and interaction between egg white protein and
      hydroxypropymethylcellulose in bulk aqueous medium on foaming properties.
AB  - Egg white protein (EW) is used as surface-active ingredient in aerated food and
      hydroxypropylmethylcellulose (HPMC) is a polysaccharide that behaves as a
      surfactant. This study aimed at investigating the effects of process parameters
      biopolymer concentration (2.0-5.0%, w/w), EW:HPMC ratio (2:1-18:1), pH (3.0-6.0),
      and the influence of biopolymers' behavior in aqueous solution at different pH on
      the foaming properties (overrun, drainage, and bubble growth rate). Process
      parameters had effect on foaming properties. The pH was the major factor
      influencing the type of EW/HPMC interaction and affected the foaming properties
      of biopolymer mixture. At pH 3.0, EW and HPMC showed thermodynamic compatibility
      leading to better foaming properties, higher foaming capacity, and stability than
      without HPMC addition whereas at pH 4.5 and 6.0, EW and HPMC are incompatible
      that causes lower stability concerning the disproportionation comparing to foam
      without HPMC. At pH between 3.0 and 4.5, HPMC improves foaming properties of
      aerated products. 

PMID- 25857958
TI  - Optimization extraction, preliminary characterization and antioxidant activity in
      vitro of polysaccharides from Stachys sieboldii Miq. tubers.
AB  - Response surface methodology was used to optimize the extraction conditions of
      water-soluble polysaccharides from Stachys sieboldii Miq. tubers. A central
      composite design was used to optimize the extraction processing parameters. The
      optimum extraction conditions are as follows: extraction temperature, 95 degrees
      C; extraction time, 2.5h; water to raw material ratio, 16; and extraction
      frequency, 3. Under the optimized conditions, an experimental yield of 9.21 +/-
      0.18%, which is in good agreement with the predicted yield, was obtained.
      Purified polysaccharide SSP II-a was successfully obtained using
      diethylaminoethanol-Sepharose and Sepharose CL-6B column chromatography. SSP II-a
      was found to be an acidic polysaccharide fraction with an average molecular
      weight of 168kDa and composed of rhamnose, glucuronic acid, galacturonic acid,
      glucose, galactose and arabinose. In vitro antioxidant activity assays suggested
      that SSP II-a presents high scavenging activity toward superoxide anion,
      hydroxyl, and 2,2'-azino-bis(3-ethylbenz-thiazoline-6-sulfonic acid) radicals but
      relatively lower scavenging activity toward 1,1-diphenyl-2-picrylhydrazyl
      radicals. The results indicated that response surface methodology is an effective
      method for the extraction of polysaccharides from S. sieboldii Miq. tubers and
      the polysaccharides could be explored as a potential antioxidant agent for use in
      medicine or functional food.

PMID- 25857959
TI  - Preparation and anti-tumor metastasis of carboxymethyl chitosan.
AB  - Carboxymethyl chitosan (CMCS), one of the most important water soluble chitosan
      derivatives, has great potentials in biomedical applications due to its excellent
      water solubility, biodegradability, biocompatibility, and non-toxicity. In the
      present study, the anti-tumor metastasis effect of CMCS on hepatic tumors was
      evaluated using human hepatic cancer cell BEL-7402 and mouse hepatoma 22 cells.
      The results suggested that CMCS could significantly inhibit tumor cell migration
      in vitro, and reduce the expression of matrix metalloproteinase-9 in BEL-7402
      cells in a dose-dependent manner (P<0.05). Furthermore, CMCS significantly
      inhibited the lung metastasis of hepatoma-22 in Kunming mice (P<0.05).
      Significant improvement of the lung injury caused by the metastasis of H22 was
      also observed. The results suggested that the inhibitory effect of CMCS could be
      attributed in part to the decreased levels of vascular endothelial growth factor
      and E-selectin in CMCS treated mice. 

PMID- 25857961
TI  - Hydrophobic modification of cellulose isolated from Agave angustifolia fibre by
      graft copolymerisation using methyl methacrylate.
AB  - Graft copolymerisation of methyl methacrylate (MMA) onto Agave angustifolia was
      conducted with ceric ammonium nitrate (CAN) as the redox initiator. The maximum
      grafting efficiency was observed at CAN and MMA concentrations of 0.91 * 10(-3)
      and 5.63 * 10(-2)M, respectively, at 45 degrees C for 3h reaction time. Four
      characteristic peaks at 2995, 1738, 1440, and 845 cm(-1), attributed to PMMA,
      were found in the IR spectrum of grafted cellulose. The crystallinity index
      dropped from 0.74 to 0.46, while the thermal stability improved upon grafting.
      The water contact angle increased with grafting yield, indicating increased
      hydrophobicity of cellulose. SEM images showed the grafted cellulose to be
      enlarged and rougher. The changes in the physical nature of PMMA-grafted
      cellulose can be attributed to the PMMA grafting in the amorphous regions of
      cellulose, causing it to expand at the expense of the crystalline component.

PMID- 25857960
TI  - Characterization of enzymatically modified rice and barley starches with
      amylosucrase at scale-up production.
AB  - Physicochemical properties of Neisseria polysaccharea amylosucrase (NpAS)-treated
      rice and barley starches were investigated at scale-up production. Pre
      gelatinized rice and barley starches were treated with significantly lower NpAS
      dose (0.1 U/mL) but 100 times larger reaction volume (3500 mL), compared to the
      analytical scale (35 mL) used in the previous study. NpAS-treated starches in
      this scale-up production were characterized with respect to reaction efficiency
      (RE), resistant starch (RS) content, amylopectin (AP) branch-chain length
      distribution, solubility, swelling power, pasting viscosity, and thermal
      transition properties. The RE enhanced up to 1.8 times by increasing the reaction
      volume, which improved the RS content and AP branch-chain lengths of NpAS-treated
      starches. Compared with the native starch, NpAS-treated starches exhibited lower
      solubility and swelling power, lower pasting viscosity, and a large increase in
      the melting peak temperature. Consequently, NpAS treatment of pre-gelatinized
      starches in this study would be a potential way of replacing commercial RS
      production.

PMID- 25857962
TI  - Modulation of the binding of basic fibroblast growth factor and heparanase
      activity by purified lambda-carrageenan oligosaccharides.
AB  - Inhibitors of angiogenesis and tumor metastasis are increasingly emerging as
      promising agents for cancer therapy. Here, we report lambda-carrageenan
      oligosaccharides (lambda-COs), highly-sulfated oligosaccharides acting as a basic
      fibroblast growth factor (bFGF) antagonist and heparanase inhibitor. lambda-COs
      with degree of polymerization (DP) from 2 to 8 degraded by lambda-carrageenase
      were separated and purified. The structures were identified by mass spectrometry.
      The activities of lambda-COs are closely related with DP. lambda-COs showed no
      cytotoxicity, but inactivated bFGF-induced cell proliferation; among them, lambda
      carraheptaose showed highest capability. Only lambda-carraheptaose can
      effectively bind to bFGF. Binding kinetics showed that lambda-carraheptaose and
      suramin had different binding modes, i.e., suramin displayed a fast association
      and fast dissociation, but lambda-carraheptaose exhibited a slow association and
      slow dissociation. In addition, lambda-COs showed the highest heparanase
      inhibitory ability and abolished the endothelial cell invasion. Thus, lambda-COs
      may provide a tool to develop of new carbohydrate-based therapeutics against
      cancer and angiogenesis.

PMID- 25857963
TI  - Effects of polymorphs on dissolution of cellulose in NaOH/urea aqueous solution.
AB  - This study focused on the effect of cellulose crystal type on the dissolution of
      cellulose in aqueous NaOH/urea. Cellulose I, II, IIII, and IVI were prepared and
      characterized. Subsequently, the solubility of these cellulose samples in aqueous
      NaOH/urea was tested and the mechanism was determined by a combination of (1)H
      NMR spectroscopy and differential scanning calorimetry (DSC). The results
      indicated that, compared with the degree of polymerization (DP) and crystallinity
      index of cellulose, the cellulose crystal type had greater impact on cellulose
      dissolution. Specially, the solubility of the cellulose I, II, and III was
      progressively decreased, probably due to different hydrogen bond network and
      packing energy in it. The ability of cellulose I, II, III, and IV to form
      hydrogen bonds with sodium hydroxides was nearly the same, while gradually
      increased when cellulose preparations were associated with urea. Moreover, all
      the cellulose solutions showed good thermal stability. 

PMID- 25857964
TI  - Core-shell cellulose nanofibers for biocomposites - nanostructural effects in
      hydrated state.
AB  - Core-shell wood cellulose nanofibers (CNF) coated by an XG hemicellulose polymer
      are prepared and used to make biocomposites. CNF/XG biocomposites have interest
      as packaging materials and as hydrated CNF/XG plant cell wall analogues.
      Structure and properties are compared between Core-shell CNF/XG and more
      inhomogeneous CNF/XG. Experiments include XG sorption, dynamic light scattering
      of CNF nanoparticle suspensions, FE-SEM of nanostructure, moisture sorption,
      tensile testing in moist conditions and dynamic mechanical analysis. (2)H NMR
      relaxometry is performed on materials containing sorbed (2)H2O2 in order to
      assess water molecular dynamics in different materials. The results clarify the
      roles of CNF, XG and the CNF/XG interface in the biocomposites, both in terms of
      moisture sorption mechanisms and mechanical properties in moist state. The
      concept of core-shell nanofiber network biocomposites, prepared by filtering of
      colloids, provides improved control of polymer matrix distribution and interface
      structure. Also, present mechanical properties are much superior to comparable
      plant fiber biocomposites.

PMID- 25857965
TI  - Novel zinc alginate hydrogels prepared by internal setting method with intrinsic
      antibacterial activity.
AB  - In this paper, a controlled gelation of alginate was performed for the first time
      using ZnCO3 and GDL. Uniform and transparent gels were obtained and investigated
      as potential wound dressings. Homogeneity, water content, swelling capability,
      water evaporation rate, stability in normal saline solution, mechanical
      properties and antibacterial activity were assessed as a function of zinc
      concentration. Gelation rate increased at increasing zinc content, while a
      decrease in water uptake and an improvement of stability were found. Release of
      zinc in physiological environments showed that concentration of zinc released in
      solution lies below the cytotoxicity level. Hydrogels showed antimicrobial
      activity against Escherichia coli. The hydrogel with highest zinc content was
      stabilized with calcium by immersion in a calcium chloride solution. The
      resulting hydrogel preserved homogeneity and antibacterial activity. Furthermore,
      it showed even an improvement of stability and mechanical properties, which makes
      it suitable as long-lasting wound dressing. 

PMID- 25857966
TI  - Effect of sodium-alginate and laminaran on Salmonella Typhimurium infection in
      human enterocyte-like HT-29-Luc cells and BALB/c mice.
AB  - Brown algal polysaccharides such as alginate, polymers of uronic acids, and
      laminaran, beta-1,3 and 1,6-glucan, can be fermented by human intestinal
      microbiota. To evaluate the effects of these polysaccharides on infections caused
      by food poisoning pathogens, we investigated the adhesion and invasion of
      pathogens (Salmonella Typhimurium, Listeria monocytogenes and Vibrio
      parahaemolyticus) in human enterocyte-like HT-29-Luc cells and in infections
      caused in BALB/c mice. Both sodium Na-alginate and laminaran (0.1% each)
      inhibited the adhesion of the pathogens to HT-29-Luc cells by approximately 70
      90%. The invasion of S. Typhimurium was also inhibited by approximately 70 and
      80% by Na-alginate and laminaran, respectively. We observed that incubation with
      Na-alginate for 18 h increased the transepithelial electrical resistance of HT-29
      Luc monolayer cells. Four days after inoculation with 7 log CFU/mouse of S.
      Typhimurium, the faecal pathogen count in mice that were not fed polysaccharides
      (control mice) was about 6.5 log CFU/g while the count in mice that were fed Na
      alginate had decreased to 5.0 log CFU/g. The liver pathogen count, which was 4.1
      log CFU/g in the control mice, was also decreased in mice that were fed Na
      alginate. In contrast, the mice that were fed laminaran exhibited a more severe
      infection than that exhibited by control mice.

PMID- 25857967
TI  - Application of X-ray and neutron small angle scattering techniques to study the
      hierarchical structure of plant cell walls: a review.
AB  - Plant cell walls present an extremely complex structure of hierarchically
      assembled cellulose microfibrils embedded in a multi-component matrix. The
      biosynthesis process determines the mechanism of cellulose crystallisation and
      assembly, as well as the interaction of cellulose with other cell wall
      components. Thus, a knowledge of cellulose microfibril and bundle architecture,
      and the structural role of matrix components, is crucial for understanding cell
      wall functional and technological roles. Small angle scattering techniques,
      combined with complementary methods, provide an efficient approach to
      characterise plant cell walls, covering a broad and relevant size range while
      minimising experimental artefacts derived from sample treatment. Given the system
      complexity, approaches such as component extraction and the use of plant cell
      wall analogues are typically employed to enable the interpretation of
      experimental results. This review summarises the current research status on the
      characterisation of the hierarchical structure of plant cell walls using small
      angle scattering techniques. 

PMID- 25857968
TI  - Cordyceps sinensis polysaccharide inhibits PDGF-BB-induced inflammation and ROS
      production in human mesangial cells.
AB  - CPS-F, a polysaccharide derived from Cordyceps sinensis, is a potential anti
      inflammatory and anti-oxidative agent. We demonstrated that CPS-F not only
      inhibits platelet-derived growth factor BB (PDGF-BB)-induced intracellular
      reactive oxygen species (ROS) generation, and up-regulation of tumor necrosis
      factor-alpha (TNF-alpha), TNF-alpha receptor 1 (TNFR1), and monocyte chemotactic
      protein-1 (MCP-1), but also acts synergistically in combination with MAPK/ERK
      inhibitor U0126 and PI3K/Akt inhibitor LY294002. Additionally, up-regulation of
      pro-inflammatory factors was reversed by use of a combination of CPS-F and NADPH
      oxidase (NOX) inhibitor diphenyleneiodonium chloride (DPI) or silencing of NOX1.
      Furthermore, CPS-F prevents the PDGF receptor beta (PDGFRbeta) promoter activity
      induced by PDGF-BB in transfected cells and ameliorates increased levels of TNF
      alpha, TNFR1, and MCP-1 when PDGFRbeta is silenced, thereby suggesting that CPS-F
      possesses a bidirectional regulatory function. Our findings suggest CPS-F may
      exert its therapeutic effect for the treatment of glomerulonephritis related to
      human mesangial cells (HMCs) through the ERK1/2/Akt pathways.

PMID- 25857969
TI  - The molecular origins of twist in cellulose I-beta.
AB  - The observation of twisted microfibrils in cellulose Ibeta both in imaging and in
      molecular simulations has been reported and studied for years. This article
      reports a computational modeling study of cellulose Ibeta twist showing its
      strong dependence on fibril diameter and no dependence on fibril length. We
      report that an important contribution to the twist in the model, empirically and
      analytically, is the hydrogen bonding that spans the glycosidic linkage, and that
      the characteristics of the chiral centers involved in the trans-glycosidic
      linkage hydrogen bonding determine the directions if those interactions and cause
      observed right-handed twist. Other crystalline forms of cellulose show evidence
      of twisting at the microfibril scale, but less than Ibeta. The minimal twist in
      other forms of cellulose was shown previously to be due to inter-layer hydrogen
      bonds; this study shows it is also partially due to the primary alcohol not
      occurring in the TG orientation in those forms. Thus, only cellulose I has the
      primary alcohol in TG orientation, which leads to formation of the twist-causing
      hydrogen bonds. 

PMID- 25857970
TI  - Solid-state photocrosslinking of hyaluronan microfibres.
AB  - Hyaluronan (HA) was chemically modified to a photocurable derivative by the
      acylation with a mixed anhydride of trans-cinnamic acid and characterized by UV,
      IR and 2D NMR spectroscopy. Photocurable HA was processed to a microfibrous
      structure by wet-spinning technology. Water solubility of otherwise water-soluble
      HA microfibres was reduced significantly by the solid-state photocrosslinking. We
      also investigated that the nature of polymer structure had a great impact to a
      final crosslink ratio. The analysis of the mechanical properties showed higher
      ultimate tensile strength and increased rigidity of the photocrosslinked fibres
      in comparison to the untreated ones. Moreover all tested materials are regarded
      as biocompatible according to the tests of cell viability, phototoxicity and
      enzymatic degradability, which make them suitable candidates for numerous
      biomedical applications.

PMID- 25857971
TI  - Synthesis, characterization, antioxidant activity and neuroprotective effects of
      selenium polysaccharide from Radix hedysari.
AB  - Beta-amyloid (Abeta) peptide, the hallmark of Alzheimer's disease, invokes
      oxidative damage to neurons and eventually leads to neuronal death. Selenylation
      modification of polysaccharide obtained from Radix hedysari (RHP) was studied to
      access antioxidant activities and neuroprotective effects against oxidative
      stress and apoptosis induced by Abeta25-35 in vitro. A series of the selenylation
      derivatives of RHP (Se-RHP) was synthesized using nitric acid-sodium selenite
      (HNO3-Na2SeO3) method. The organic selenium content of Se-RHP increased from 1.04
      to 3.29 mg/g. However, compared with the weight-average molecular mass (Mw) of
      RHP, Mw of Se-RHP showed a significant decrease, and varied from 27.7 kDa to 62.7
      kDa. FT-IR spectra and (13)C NMR spectra indicated the selenite groups had been
      introduced mainly at the C-6 positions of RHP. Compared with RHP, Se-RHP showed
      greater antioxidant activities in vitro. Furthermore, both RHP and Se-RHP3 had
      neuroprotective effects against Abeta25-35-induced oxidative stress and apoptosis
      in SH-SY5Y human neuroblastoma cells, which might be a potential therapeutic
      agent for preventing or treating neurodegenerative diseases.

PMID- 25857972
TI  - Impact of phase separation of soy protein isolate/sodium alginate co-blending
      mixtures on gelation dynamics and gels properties.
AB  - The influence of sodium alginate (SA) on soy protein isolate (SPI)-based co
      blending system gelling properties was studied under thermodynamic compatibility
      and incompatibility conditions using a direct addition (SPI/SA) or co-drying
      (SPI/SA-CO) process. For an SPI/SA (30:1) or SPI/SA-CO (30:1) system, the
      addition of too little SA did not significantly modify the SPI, and the gelation
      temperature (Tgel) and storage modulus (G') were similar to an SPI solution
      alone. For SPI/SA (20:1) and SPI/SA-CO (10:1), the Tgel and G' were between the
      values for solutions of SPI or SA alone; however, SPI/SA-CO (20:1) and SPI/SA-CO
      (10:1) gels could nearly double the equilibrium value of G' (Geq'), thus
      improving the barrier and mechanical properties of the final formed films. The
      cryo-transmission electron microscope morphology of the SPI/SA-CO (20:1) and
      SPI/SA-CO (10:1) systems after heating was of the core-shell type in which the
      core comprised SPI gel. 

PMID- 25857973
TI  - Effects of the order of addition of reagents and alkali on modification of wheat
      starches.
AB  - The objective of this research was to determine if adding reactive reagents to
      wheat starch granules before addition of alkali (the TRF method) would produce
      products that are different than those obtained with the conventional procedure
      (adding alkali before addition of reagent). Laboratory-isolated (LI) and
      commercial (C) normal (NWS) and waxy (WWS) wheat starches were each reacted with
      6 reagents (acetic-adipic mixed anhydride (AAMA), phosphoryl chloride (POCl3),
      sodium trimetaphosphate (STMP), acetic anhydride (AA), succinic anhydride (SA),
      octenylsuccinic anhydride (OSA)). Data obtained were similar to those previously
      obtained with maize starches (Sui, Huber, & BeMiller, 2013). Almost no starch
      polymer molecule modification occurred when the TRF method and AAMA or AA were
      used; less than a third as much reaction when SA was the reagent used, and about
      the same amount of reaction when POCl3, STMP, or OSA were the reagents used (for
      different reasons). 

PMID- 25857975
TI  - Structural characteristics of slowly digestible starch and resistant starch
      isolated from heat-moisture treated waxy potato starch.
AB  - The objective of this study was to investigate the structural characteristics of
      slowly digestible starch (SDS) and resistant starch (RS) fractions isolated from
      heat-moisture treated waxy potato starch. The waxy potato starch with 25.7%
      moisture content was heated at 120 degrees C for 5.3h. Scanning electron
      micrographs of the cross sections of RS and SDS+RS fractions revealed a growth
      ring structure. The branch chain-length distribution of debranched amylopectin
      from the RS fraction had a higher proportion of long chains (DP >= 37) than the
      SDS+RS fraction. The X-ray diffraction intensities of RS and SDS+RS fractions
      were increased compared to the control. The SDS+RS fraction showed a lower
      gelatinization enthalpy than the control while the RS fraction had a higher value
      than the SDS+RS fraction. In this study we showed the RS fraction is composed
      mainly of crystalline structure and the SDS fraction consists of weak
      crystallites and amorphous regions.

PMID- 25857976
TI  - Enhanced chromium (VI) adsorption using nanosized chitosan fibers tailored by
      electrospinning.
AB  - Stacked chitosan nanofibers with an average diameter of 75 nm were successfully
      produced by electrospinning using 5 wt% chitosan in acetic acid as the spinning
      solution. The fibers were then cross-linked with glutaraldehyde to remove
      chromium [Cr(VI)] from water via static adsorption. It was found that the
      adsorption correlated well with pseudo-second order kinetic model, and followed a
      mixed isotherm of Freundlich and Langmuir. The maximum nanofibers adsorption
      capacity was 131.58 mg/g, more than doubled that of chitosan powders. Common co
      ions such as Cl(-), NO3(-), Na(+), Ca(2+) and Mg(2+) had little or no effect on
      the adsorption but SO4(2-) was an exception. Fourier transform infrared
      spectroscopy and X-ray photoelectron spectrophotometer analyses indicated that
      both amino and hydroxyl groups of chitosan were engaged in the adsorption.

PMID- 25857974
TI  - Carboxyl-modified poly(vinyl alcohol)-crosslinked chitosan hydrogel films for
      potential wound dressing.
AB  - The objective of this study was to develop a novel carboxyl-modified poly(vinyl
      alcohol)-crosslinked chitosan hydrogel films for potential wound dressing. To
      prepare the crosslinked hydrogels, poly(vinyl alcohol) (PVA) was grafted with
      succinate acid to yield carboxyl-modified poly(vinyl alcohol) (PVA-COOH).
      Hydrogel films based on PVA-COOH and chitosan (CS) at different concentrations
      were crosslinked through the formation of amide linkages. The mechanical
      properties of these crosslinked hydrogel films in dry and swollen state were
      greatly improved with high swelling ratio. Water vapor and oxygen permeability
      evaluations indicated that crosslinked hydrogel films could maintain a moist
      environment over wound bed. Biocompatibility test showed the crosslinked
      hydrogels had no cytotoxicity and hemolytic potential. Gentamicin sulfate-loaded
      crosslinked hydrogel films showed sustained drug release profile, and could
      effectively suppress bacterial proliferation and protect wound from infection. 

PMID- 25857977
TI  - Thermodynamic and structural properties of tuber starches from transgenic potato
      plants grown in vitro and in vivo.
AB  - Potato plants harboring Phytochrome B (PHYB) gene from Arabidopsis thaliana or
      rol genes from Agrobacterium rhizogenes were used to study the effect of
      transgene expression on structure and properties of starch in tubers.
      Thermodynamic characteristics of starch (melting temperature, enthalpy of
      melting, thickness of crystalline lamellae) were shown to be variable depending
      on the transgene expression and plant culturing mode: in vitro or in soil. The
      expression of rolB or rolC genes in in vitro cultured plants evoked opposite
      effects on starch melting temperature and crystalline lamellae thickness. AtPHYB
      or rolB expression in the soil-grown potato led to the formation of more
      defective or more ordered starch structures, respectively, in comparison with
      starches of the same lines grown in vitro. On the whole, our study revealed
      genotype-dependent differences between starches extracted from tubers of in vitro
      or in vivo grown plants. 

PMID- 25857979
TI  - Rapeseed polysaccharides as prebiotics on growth and acidifying activity of
      probiotics in vitro.
AB  - In vitro digestibility, prebiotic activity and chemical composition of
      polysaccharides from rapeseed were deliberately studied in this paper. After
      preliminary treatments, two fractions of polysaccharides (RP1 and RP2) were
      obtained after purification by DEAE-cellulose and Sephadex G-100. Their primary
      structural feature and molecule weights were characterized. Furthermore, their
      digestibility was also evaluated by artificial gastric juice and alpha-amylase.
      Finally, their proliferative effect on bifidobacteria and lactobacilli and acid
      production of the resulting probiotics in vitro were investigated. The results
      showed that RP1 and RP2 were homogeneously protein-bound polysaccharides with
      molecular weights of 28.51 and 6.55 kDa, respectively. They were resistant to
      hydrolysis by artificial gastric juice and alpha-amylase. Moreover, they could
      also significantly stimulate the tested probiotics to proliferate and produce
      organic acids. These findings clearly suggest the polysaccharides from rapeseed
      are potential to be exploited as novel prebiotics.

PMID- 25857978
TI  - Effect of the degree of substitution in the transition temperatures and
      hydrophobicity of hydroxypropyl cellulose esters.
AB  - We have synthesized and characterized five members of a homologous series of side
      chain polymers of hydroxypropyl cellulose esters obtained by homogeneous
      esterification with 6-[4'-(ethoxycarbonyl)biphenyl-4-yloxy]hexanoic acid. Two
      acylation procedures were studied. One procedure involved the acid chloride
      derivative and the other one was the activation of that acid with N,N'
      carbonyldiimidazol. The second method yielded esters with higher degree of
      substitution, DS-. The esters, with DS- ranging from 26 to about 66%, were
      characterized by FTIR, NMR, solution viscometry, TGA, DSC, polarized optical
      microscopy, and X-ray diffraction, in order to study the effect of the degree of
      substitution on the hydrophobicity, on the transition temperatures and on their
      potential liquid crystal properties. It has been found that the hydrophobicity
      and the transition temperatures of the HPC derivatives are very much dependent on
      the degree of acylation. The esters with high DS- values showed liquid crystal
      properties.

PMID- 25857980
TI  - Effect of the native polysaccharide of cashew-nut tree gum exudate on murine
      peritoneal macrophage modulatory activities.
AB  - The native polysaccharide of cashew-nut tree gum exudate (CNTG) and its
      arabinogalactan-protein component (CNTG-AGP) were tested by using immuno
      stimulant and anti-inflammatory in vitro assays of murine peritoneal macrophage
      activities. In the assay for immuno-stimulant activity (without previous
      treatment with lipopolysaccharide; LPS), CNTG increased the production of
      interleukin (IL)-10 and both CNTG and CNTG-AGP decreased the concentrations of
      IL6. When the macrophages were incubated in the presence of LPS and CNTG a
      decrease in the levels of nitric oxide (NO(.)) and IFN-gamma was observed. The
      results could explain the popular use of CNTG as an anti-inflammatory. In
      addition, CNTG is the main component of the cashew-nut tree gum exudate, which
      has been considered a versatile polymer with potential pharmaceutical and food
      industry applications. These data may contribute to the study of the
      immunomodulation activity of plant polysaccharides, as well as encourage future
      experiments in the field of cashew-nut tree gum exudate applications. 

PMID- 25857981
TI  - Facile cellulose dissolution without heating in [C4mim][CH 3COO]/DMF solvent.
AB  - Novel cellulose solvents, [C4mim][CH3COO]/DMF, were designed by adding an aprotic
      polar solvent N,N-dimethylformamide (DMF) in 1-butyl-3-methylimidazolium acetate
      ([C4mim][CH3COO]). The solubilities of cellulose in [C4mim][CH3COO]/DMF solvents
      were determined at 25 degrees C. The effects of molar ratio of DMF to
      [C4mim][CH3COO] on cellulose solubility and the possible dissolution mechanism of
      cellulose in [C4mim][CH3COO]/DMF solvent have been studied. Moreover, the
      regenerated cellulose from [C4mim][CH3COO]/DMF solvent were characterized by
      scanning electron micrograph (SEM) Fourier transform infrared spectroscopy (FTIR)
      and X-ray diffraction (XRD), and the degree of polymerization (DP) of regenerated
      cellulose was determined. The findings reveal that the facile dissolution of
      cellulose in such solvents is mainly attributed to the increased "free" [CH3COO](
      ) anions and [C4mim](+) cations which result from the dissociation of
      [C4mim][CH3COO] by DMF. Moreover, the macromolecular chain of the cellulose is
      hardly broken during the dissolution and precipitation processes.

PMID- 25857982
TI  - Sodium carboxymethylcellulose-induced aggregation of 1-decyl-3-methylimidazolium
      chloride in aqueous solutions.
AB  - Aggregation behavior of a surface active ionic liquid 1-decyl-3-methylimidazolium
      chloride (C10MeImCl) was studied in aqueous solutions in absence and in presence
      of sodium carboxymethylcellulose (NaCMC) by electrical conductivity, surface
      tension, vapor pressure, and fluorescence measurements. Ion-association behavior
      of C10MeImCl (aq) in the premicellar regime has also been investigated. Two
      characteristic concentrations, namely the critical aggregation concentration and
      polymer saturation concentration, before free C10MeImCl micelles appear in
      C10MeImCl-NaCMC solutions were identified. Effects of temperature, NaCMC
      concentration, and the bulk solution structural property on the self-aggregation
      of C10MeImCl have been discussed to elucidate C10MeImCl-NaCMC interactions.
      Thermodynamics of the micellization processes provided important insight
      regarding the (a) release of water molecules from the hydration layer around the
      hydrophilic domain, and from the water cage around the hydrophobic moiety of the
      SAIL, and (b) transfer of the hydrocarbon chains into the micelle and restoration
      of the H-bonding structure of the water around the micelle.

PMID- 25857983
TI  - Effect of surfactant treatment on swelling behaviour of normal and waxy cereal
      starches.
AB  - Starch swelling behaviour greatly affects its functionality in a food matrix. For
      some granular starches pre-treatment with the surfactant, sodium dodecyl
      sulphate, is known to dramatically affect swelling behaviour. The purpose of this
      study was to assess the effect of this surfactant treatment on the swelling
      behaviour of a variety of waxy and normal cereal starches. A concurrent mid
      infrared spectroscopy study was carried out to investigate the chemical nature of
      variations in swelling behaviour. The native normal starches (amylose content 23
      28%) showed significant variation in their pasting properties, which was largely
      eliminated by surfactant treatment. Surfactant treatment had less effect on the
      behaviour of the waxy starches (amylose contents 1-8%), which still exhibited
      some residual variation. Waxy durum appeared to be unique within the waxy
      starches, behaving more similarly to the normal starches. The spectroscopic data
      highlighted the carbohydrate fingerprint region as the main source of variation
      between samples. 

PMID- 25857984
TI  - Development of a stable low-fat yogurt gel using functionality of psyllium
      (Plantago ovata Forsk) husk gum.
AB  - Psyllium husk gum (PHG) as an ideal fat replacer was utilized to improve the
      production of an industrial low-fat yogurt gel. The combined effects of critical
      structural components (PHG concentration (0.072-0.128%) and fat content (0.29
      1.71%)) on the textural (firmness and syneresis), rheological (viscosity), and
      chemical (pH and total titratable acidity (TTA)) attributes of developed set
      yogurts were investigated using response surface methodology (RSM). The second
      order polynomial equations with high R(2) demonstrated a good agreement between
      experimental and predicted data. The optimal formulation for achieving optimal pH
      (4.39) and TTA (81% lactic acid), maximizing firmness (0.172 N) and viscosity
      (6.40 Pa s) and minimizing whey separation (36.21 mL/100g) was 0.12% PHG and
      0.63% fat. Sensory characterization also revealed that the yogurts manufactured
      at optimal point had more aroma, texture and overall acceptability than the
      control yogurts.

PMID- 25857985
TI  - Formation of spherical and core-shell polymeric microparticles from
      glycopolymers.
AB  - 6-O-methacryloyl-alpha-d-glucoside 2 and 4-bromophenyl-6-O-methacryloyl-d
      glucothioside 7, obtained by enzyme-catalyzed synthesis, have been homo
      polymerized and copolymerized with styrene by a free radical process, yielding
      polymer materials with sugar moieties, attached to the polymer backbone via ester
      linkages. The results demonstrated that modifying the structural features of the
      monomers greatly affected the thermal and rheological properties of the polymers.
      The polymer materials obtained have been characterized by NMR, MALDI-MS, DSC,
      AFM, and EWC (equilibrium water content). The AFM images indicated the formation
      of spherical and core-shell polymeric microparticles.

PMID- 25857986
TI  - Complexation of synthetic CDM-AM copolymer with natamycin and carbendazim to
      improve solubility and fungicidal activity.
AB  - The beta-cyclodextrin-acrylamide (CDM-AM) copolymer was prepared from acrylamide
      and beta-CD maleate (CDM) using K2S2O8 as initiator. The effects of the CDM-AM
      copolymer on the solubility and fungicidal activity of natamycin (NM) and
      carbendazim (MBC) were investigated. The stability constant of NM.CDM-AM and
      MBC.CDM-AM complexes at 303 K were of 10,725.45 M(-1) and 3000.89 M(-1),
      respectively. The complexes were characterized using phase solubility diagrams,
      NMR spectra and FT-IR spectra. The analysis of the biological activities of these
      two complexes indicated that they possessed enhancing fungicidal activities
      compared to NM and MBC alone.

PMID- 25857987
TI  - Characterisation and properties of homo- and heterogenously phosphorylated
      nanocellulose.
AB  - Nano-sized cellulose ester derivatives having phosphoryl side groups were
      synthesised by phosphorylation of nanofibrilated cellulose (NFC) and
      nanocrystaline cellulose (NCC), using different heterogeneous (in water) and
      homogeneous (in molten urea) processes with phosphoric acid as phosphoryl donor.
      The phosphorylation mechanism, efficacy, stability, as well as its influence on
      the NC crystallinity and thermal properties, were evaluated using ATR-FTIR and
      (13)C NMR spectroscopies, potentiometric titration, capillary electrophoresis, X
      ray diffraction, colorimetry, thermogravimmetry and SEM. Phosphorylation under
      both processes created dibasic phosphate and monobasic tautomeric phosphite
      groups at C6 and C3 positioned hydroxyls of cellulose, yielded 60-fold (~1,173
      mmol/kg) and 2-fold (~1.038 mmol/kg) higher surface charge density for p-NFC and
      p-NCC, respectively, under homogenous conditions. None of the phosphorylations
      affected neither the NC crystallinity degree nor the structure, and noticeably
      preventing the derivatives from weight loss during the pyrolysis process. The p
      NC showed high hydrolytic stability to water at all pH mediums. Reusing of the
      treatment bath was examined after the heterogeneous process.

PMID- 25857988
TI  - Structure-activity relationship of immunomodulating pectins from elderberries.
AB  - The berries of Sambucus nigra have traditionally been used and are still used to
      treat respiratory illnesses such as cold and flu in Europe, Asia and America. The
      aim of this paper was to elucidate the structures and the immunomodulating
      properties of the pectic polymers from elderberries. All the purified fractions
      obtained from 50% ethanol, 50 degrees C water and 100 degrees C water extracts
      showed potent dose-dependent complement fixating activity and macrophage
      stimulating activity. The isolated fractions consisted of long homogalacturonan
      regions, in addition to arabinogalactan-I and arabinogalactan-II probably linked
      to a rhamnogalacturonan backbone. Reduced bioactivity was observed after
      reduction of Araf residues and 1->3,6 Gal by weak acid hydrolysis. The
      rhamnogalacturonan region in SnBe50-I-S3-I and SnBe50-I-S3-II showed higher
      activity compared to the native polymer, SnBe50-S3, after enzymatic treatment
      with endo-alpha-d-(1->4)-polygalacturonase. These results indicated that
      elderberries contained immunomodulating polysaccharides, where the ramified
      regions express the activities observed. 

PMID- 25857989
TI  - Surface characterization and drug release from porous microparticles based on
      methacrylic monomers and xanthan.
AB  - Porous crosslinked microparticles based on glycidyl methacrylate and xanthan were
      prepared by suspension polymerization and used for loading theophylline, a
      bronhodilatator drug, in order to obtain new drug delivery systems. The surface
      morphologies observed by means of SEM and AFM analysis demonstrated that
      microparticles show a spherical shape and are characterized by a porous
      structure. The presence of xanthan in the structure of microparticles leads to a
      decrease of surface roughness and pore diameters as well as to an increase of
      hydrophilicity degree compared to the micropaticles based only on glycidyl
      methacrylate. To analyze the in vitro release data various mathematical models
      were used, such as, first order, Higuchi model, Korsmeyer-Peppas model and Baker
      Lonsdale model. Based on the highest values of the correlation coefficient, the
      analysis of the kinetic data indicate that drug release from G1 and X1 porous
      microparticles fits similarly well to the first order and Higuchi models and
      diffusion was the dominant mechanism of drug release. 

PMID- 25857990
TI  - Carboxymethylated glucomannan as paper strengthening agent.
AB  - Strength additives play an important role in allowing the papermaking industry to
      achieve its objectives. In this study, a new kind of paper strengthening agent
      based on glucomannan was developed by treating it with sodium chloroacetate under
      alkaline conditions, and the effects on paper properties were evaluated. Results
      indicated that carboxymethylated glucomannan could significantly improve the
      paper properties. Compared to the untreated paper, the density, burst index,
      tensile index, and folding endurance were increased by 15.2%, 22.8%, 34.6%,
      179.0%, respectively, when 0.9% carboxymethylated glucomannan was used. Polyamide
      epichlorohydrin (PAE) was used to improve the wet strength of the paper. When
      0.6% PAE and 0.6% carboxymethylated glucomannan were used, the burst index, dry
      tensile index, wet tensile index of paper were increased by 14.1%, 25%, 34.3%,
      respectively, as compared to that of the control, while the folding endurance
      decreased slightly. In addition, dry tensile index and wet tensile index were
      increased with increasing the carboxymethylation time of glucomannan. The results
      demonstrated that PAE and carboxymethylated glucomannan displayed a synergistic
      effect. SEM analysis illustrated that paper strengthening agent could increase
      the combination of fibers in paper.

PMID- 25857991
TI  - New findings about the lipase acetylation of nanofibrillated cellulose using
      acetic anhydride as acyl donor.
AB  - The acetylation efficiency of nanofibrillated cellulose (NFC) with acetic
      anhydride as acetyl donor was studied using lipase from Aspergillus niger in a
      mixture of dimethyl sulphoxide (DMSO) and phosphate buffer solution at ambient
      conditions and in supercritical carbon dioxide (scCO2). The chemical acetylation
      of NFC with comparable ester content was carried out for comparison. The ATR
      FTIR, solid-state CP/MAS (13)C NMR and DSC analyses revealed that, besides the
      enzyme-catalysed acetylation, predominantly appearing at the C-6 position of
      cellulose hydroxyls, a strong and stable acyl-enzyme intermediate attachment also
      occurred on the NFC via Maillard reaction. Enzymatic acetylation via attached
      acyl-enzyme complex on NFC yielded high hydophobicity (contact angle of 84+/-9
      degrees ), whereas the chemical acetylation with comparable ester content
      resulted in a much lower hydrophobic surface with a contact angle of 33+/-3
      degrees . Finally, the adsorption capacity profiles of lysozyme and BSA proteins
      on native, chemically and enzymatically acetylated NFC as a function of the pH
      medium were determined. 

PMID- 25857992
TI  - Preparing cellulose nanocrystal/acrylonitrile-butadiene-styrene nanocomposites
      using the master-batch method.
AB  - The master-batch method provides a simple way to apply cellulose nanocrystal
      (CNC) as reinforcement in a hydrophobic matrix. The two-stage process includes
      making high-CNC content (70 wt%) master batch pellets, then mixing acrylonitrile
      butadiene-styrene (ABS) and maleic anhydride grafted polyethylene with the master
      batch pellets to prepare the ABS/CNC nanocomposite in extruder. SEM image
      indicates that self-assembled CNC nanosheets disperse evenly throughout the
      polymer matrix. The improved mechanical properties shown in tensile and DMA tests
      reveal that the CNC combines well with the ABS. TGA results show that the thermal
      degradation temperature of CNC in the master batch increases because of the
      protection of the ABS coating. This approach not only improves the dispersion
      ability and the thermal stability of CNC, but it is also applicable to use with
      other hydrophobic thermoplastics in industrial scale production.

PMID- 25857994
TI  - The synchronized wash-off of reactive-dyed cotton fabrics and decolorization of
      resultant wastewater using titanium dioxide nano-fibers.
AB  - In this research, titanium dioxide (TiO2) nano-fibers with a well-organized
      anatase structure were synthesized by a hydrothermal method. Their structural
      properties were characterized by X-ray diffraction (XRD), Brunauer-Emmett-Teller
      (BET), and transmission electron microscope (TEM) analysis, respectively.
      Subsequently, the TiO2 nano-fibers were optically excited under the ultraviolet
      (UV) irradiation to decolorize the reactive dye solution. The influences of
      initial pH, concentrations of reactive dye and TiO2 nano-fibers as well as
      irradiation time on rate of photocatalytic decolorization were investigated.
      Based on their excellent photocatalytic performance, a novel method for achieving
      the synchronized wash-off of reactive-dyed cotton and decolorization of resultant
      wastewater was developed. It was found that the wash fastness of reactive-dyed
      cotton after TiO2-based wash-off was equal to that after standard way. The
      influences of TiO2-based wash-off on the properties of cotton substrates were
      determined by Fourier transform infrared spectroscopy (FTIR), XRD, and scanning
      electron microscope (SEM) analysis, respectively, which indicated that this new
      synchronized method would exert few damages to the cotton substrate.

PMID- 25857993
TI  - Extraction of cellulose nano-crystals from old corrugated container fiber using
      phosphoric acid and enzymatic hydrolysis followed by sonication.
AB  - Due to its amazing physicochemical properties and high environmental
      compatibility, cellulose nano-crystals (CNC) hold great promise for serving as a
      strategic platform for sustainable development. Now, there has been growing
      interest in the development of processes using waste or residual biomass as CNC
      source for addressing economic and environmental concerns. In the present work, a
      combined process involving phosphoric acid hydrolysis, enzymatic hydrolysis and
      sonication was proposed aiming to efficiently exact CNC from low-cost old
      corrugated container (OCC) pulp fiber. The effect of enzymatic hydrolysis on the
      yield and microstructure of resulting CNC was highlighted. Results showed that
      the enzymatic hydrolysis was effective in enhancing CNC yield after phosphoric
      acid hydrolysis. CNC was obtained with a yield of 23.98 wt% via the combined
      process with phosphoric acid concentration of 60 wt%, cellulase dosage of 2 mL
      (84 EGU) per 2g fiber and sonication intensity of 200 W. Moreover, the presence
      of enzymatic hydrolysis imparted the obtained CNC with improved dispersion,
      increased crystallinity and thermal stability.

PMID- 25857995
TI  - Starch-based hydrogel loading with carbendazim for controlled-release and water
      absorption.
AB  - Starch, with properties of eco-friendliness and abundance, is one of the most
      important natural polymers. Starch-based hydrogels were investigated as carriers
      of carbendazim to combine controlled-release and water absorption (WA). Three
      carbendazim-loaded hydrogels (CLHs) with different WA capacities were prepared by
      solution polymerization. The CLHs were characterized by Fourier transform
      infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), and liquid
      chromatography mass-spectrometry (LC-MS/MS). Release kinetics of CLHs was
      investigated using (14)C-labeling method. The diffusion parameters of CLHs were
      0.47, 0.57 and 0.81 in deionized H2O (ddH2O). WA affected release profile
      significantly, the release longevity reaching 240 h when WA was 800 g/g in ddH2O.
      Solution pH influenced release profiles and the lowest release rate occurred in
      the lowest pH. Addition of CLH (1.3g/kg soil) markedly increased water-holding
      capacity (WHC) of soil by 8.2%. The study indicated that starch-based CLH was a
      good controlled-release agent for carbendazim and water absorbent for soil.

PMID- 25857996
TI  - The external microenvironment of healing skin wounds.
AB  - The skin wound microenvironment can be divided into two main components that
      influence healing: the external wound microenvironment, which is outside the
      wound surface; and the internal wound microenvironment, underneath the surface,
      to which the cells within the wound are exposed. Treatment methods that directly
      alter the features of the external wound microenvironment indirectly affect the
      internal wound microenvironment due to the exchange between the two compartments.
      In this review, we focus on the effects of temperature, pressure (positive and
      negative), hydration, gases (oxygen and carbon dioxide), pH, and anti-microbial
      treatment on the wound. These factors are well described in the literature and
      can be modified with treatment methods available in the clinic. Understanding the
      roles of these factors in wound pathophysiology is of central importance in wound
      treatment. 

PMID- 25857998
TI  - Along came a spider who sat down beside her: Perceived predation risk, but not
      female age, affects female mate choosiness.
AB  - Organisms often exhibit behavioral plasticity in response to changes in factors,
      such as predation risk, mate density, and age. Particularly, female mate
      choosiness (the strength of female's attraction to male traits as they deviate
      from preferred trait values) has repeatedly been shown to be plastic. This is due
      to the costs associated with searching for preferred males fluctuating with
      changes in such factors. Because these factors can interact naturally, it is
      important to understand how female mate choosiness responds to these
      interactions. We studied the interaction between perceived predation risk and
      female age on the variable field cricket, Gryllus lineaticeps. Females were
      either exposed or not exposed to predation cues from a sympatric, cursorial, wolf
      spider predator, Hogna sp. We then tested the females at one of three adult ages
      and measured their choosiness by recording their responsiveness to a low quality
      male song. We found female choosiness plasticity was affected by neither age nor
      the interaction between age and perceived predation risk. Perceived predation
      risk was the only factor to significantly affect the plasticity of female mate
      choosiness: females were less choosy when they perceived predation risk and were
      more choosy when they did not. Predation may be such a strong source of selection
      that, regardless of differences in other factors, most individuals respond
      similarly. 

PMID- 25857997
TI  - UPR(mt)-mediated cytoprotection and organismal aging.
AB  - Time- or age-dependent accumulation of mitochondrial damage and dysfunction is
      strongly associated with aging [1]. Thus, a major biomedical goal is to identify
      and therapeutically manipulate those inherent programs that protect against
      mitochondrial dysfunction to promote cell survival and organismal health. The
      mitochondrial unfolded protein response (UPR(mt)) is such a protective
      transcriptional response mediated by mitochondrial-to-nuclear signaling that
      includes mitochondrial proteostasis genes to stabilize mitochondrial function,
      metabolic adaptations, as well as an innate immunity program. Here, we review the
      UPR(mt) and its role during a variety of forms of mitochondrial dysfunction
      including those caused by mutations in respiratory chain genes as well as upon
      exposure to pathogens that produce mitochondrial toxins. We also review recent
      data in support of and against the emerging role of the UPR(mt) during aging and
      longevity. This article is part of a Special Issue entitled: Mitochondrial
      Dysfunction in Aging. 

PMID- 25857999
TI  - Chronic ethanol consumption disrupts diurnal rhythms of hepatic glycogen
      metabolism in mice.
AB  - Chronic ethanol consumption has been shown to significantly decrease hepatic
      glycogen content; however, the mechanisms responsible for this adverse metabolic
      effect are unknown. In this study, we examined the impact chronic ethanol
      consumption has on time-of-day-dependent oscillations (rhythms) in glycogen
      metabolism processes in the liver. For this, male C57BL/6J mice were fed either a
      control or ethanol-containing liquid diet for 5 wk, and livers were collected
      every 4 h for 24 h and analyzed for changes in various genes and proteins
      involved in hepatic glycogen metabolism. Glycogen displayed a robust diurnal
      rhythm in the livers of mice fed the control diet, with the peak occurring during
      the active (dark) period of the day. The diurnal glycogen rhythm was
      significantly altered in livers of ethanol-fed mice, with the glycogen peak
      shifted into the inactive (light) period and the overall content of glycogen
      decreased compared with controls. Chronic ethanol consumption further disrupted
      diurnal rhythms in gene expression (glycogen synthase 1 and 2, glycogenin,
      glucokinase, protein targeting to glycogen, and pyruvate kinase), total and
      phosphorylated glycogen synthase protein, and enzyme activities of glycogen
      synthase and glycogen phosphorylase, the rate-limiting enzymes of glycogen
      metabolism. In summary, these results show for the first time that chronic
      ethanol consumption disrupts diurnal rhythms in hepatic glycogen metabolism at
      the gene and protein level. Chronic ethanol-induced disruption in these daily
      rhythms likely contributes to glycogen depletion and disruption of hepatic energy
      homeostasis, a recognized risk factor in the etiology of alcoholic liver disease.

PMID- 25858000
TI  - Liver Stiffness: A Significant Relationship with the Waveform Pattern in the
      Hepatic Vein.
AB  - The aim of this prospective study was to assess the relationship between liver
      stiffness and hepatic vein waveform patterns in 42 patients with chronic
      hepatitis and 55 with cirrhosis. Liver stiffness measurement (LSM) values
      (FibroScan, Echosens, Paris, France) were significantly lower in the triphasic
      pattern group (11.3 +/- 8.4 kPa) than in the monophasic pattern (32.5 +/- 23.5
      kPa, p = 0.001) and biphasic pattern (25.6 +/- 18.1 kPa, p = 0.001) groups,
      indicating no significant relationship with portal pressure. The ability to
      diagnose cirrhosis represented by the highest area under the receiver operating
      characteristic curve was 0.921 (83.6% sensitivity, 90.5% specificity, best cutoff
      value: 16.9 kPa) by LSM and 1.000 (best cutoff value: 19.4 kPa) by LSM combined
      with the monophasic pattern. This study revealed a close linkage between liver
      stiffness and hepatic vein waveform findings, resulting in a better understanding
      of hepatic vein hemodynamics and wider application of its analysis.

PMID- 25858001
TI  - Quantification of Microvascular Tortuosity during Tumor Evolution Using Acoustic
      Angiography.
AB  - The recent design of ultra-broadband, multifrequency ultrasound transducers has
      enabled high-sensitivity, high-resolution contrast imaging, with very efficient
      suppression of tissue background using a technique called acoustic angiography.
      Here we perform the first application of acoustic angiography to evolving tumors
      in mice predisposed to develop mammary carcinoma, with the intent of visualizing
      and quantifying angiogenesis progression associated with tumor growth. Metrics
      compared include vascular density and two measures of vessel tortuosity
      quantified from segmentations of vessels traversing and surrounding 24 tumors and
      abdominal vessels from control mice. Quantitative morphologic analysis of tumor
      vessels revealed significantly increased vascular tortuosity abnormalities
      associated with tumor growth, with the distance metric elevated approximately 14%
      and the sum of angles metric increased 60% in tumor vessels versus controls.
      Future applications of this imaging approach may provide clinicians with a new
      tool in tumor detection, differentiation or evaluation, though with limited depth
      of penetration using the current configuration. 

PMID- 25858002
TI  - Cryptotanshinone protects against adriamycin-induced mitochondrial dysfunction in
      cardiomyocytes.
AB  - CONTEXT: The serious side effect of Adriamycin (ADR) is cardiomyopathy.
      Cryptotanshinone (CRY) is widely and safely used as antioxidant with MTD more
      than 5 mg/g in rats (p.o). OBJECTIVE: The objective of this study is to study the
      protection effects of CRY against ADR-induced mitochondrial dysfunction in
      cardiomyocytes. MATERIALS AND METHODS: The chemical administration lasted for 20
      days with an effective dose of CRY (p.o.) at 50 mg/kg in rats. Mitochondrial
      respiratory chain complex activities, ATP generation, mitochondrial membrane
      potential (MMP), superoxide anion free radical, oxidative stress-relative
      enzymes, and mitochondrial biogenesis-relative factors in normal control, ADR
      (i.p., 1.25 mg/kg), and ADR (i.p., 1.25 mg/kg) + CYP (p.o., 50 mg/kg) groups were
      detected. RESULTS: 50 mg/kg CRY significantly promoted the energy production of
      ATP (16.99 +/- 2.38 nmol/g Pro) (Pro: Protein) by increasing the complexes
      activities except II (p > 0.05). After the treatment of CRY, the suppressed MMP
      was increased while superoxide anion free radical (0.57 +/- 0.07/mg Pro) was
      inhibited markedly. Mitochondrial biogenesis-relative factors PGC-1alpha, NRF-1,
      and TFAM were also promoted. Remarkable augmentations of NO, inducible nitric
      oxide synthase (iNOS), and increased activity of GSH-PX (p < 0.05) were also
      detected after the treatment of CRY, while no obvious changes on the activity of
      nitric oxide synthase (cNOS; p > 0.05) were observed. DISCUSSION AND CONCLUSION:
      These results suggest that CRY protects against ADR-induced mitochondrial
      dysfunction in cardiomyocytes. It could be an ideal potential drug of
      cardioprotection.

PMID- 25858003
TI  - Randomized placebo controlled blinded study to assess valsartan efficacy in
      preventing left ventricle remodeling in patients with dual chamber pacemaker-
      Rationale and design of the trial.
AB  - BACKGROUND: Dual chamber pacing is known to have detrimental effect on cardiac
      performance and heart failure occurring eventually is associated with increased
      mortality. Experimental studies of pacing in dogs have shown contractile
      dyssynchrony leading to diffuse alterations in extracellular matrix. In parallel,
      studies on experimental ischemia/reperfusion injury have shown efficacy of
      valsartan to inhibit activity of matrix metalloproteinase-9, to increase the
      activity of tissue inhibitor of matrix metalloproteinase-3 and preserve global
      contractility and left ventricle ejection fraction. PURPOSE: To present rationale
      and design of randomized blinded trial aimed to assess whether 12 month long
      administration of valsartan will prevent left ventricle remodeling in patients
      with preserved left ventricle ejection fraction (LVEF >= 40%) and first
      implantation of dual chamber pacemaker. METHODS: A total of 100 eligible patients
      will be randomized into three parallel arms: placebo, valsartan 80 mg/daily and
      valsartan 160 mg/daily added to previously used drugs. The primary endpoint will
      be assessment of valsartan efficacy to prevent left ventricle remodeling during
      12 month follow-up. We assess patients' functional capacity, blood plasma
      activity of matrix metalloproteinases and their tissue inhibitors, NT-proBNP,
      tumor necrosis factor alpha, and Troponin T. Left ventricle function and
      remodeling is assessed echocardiographically: M-mode, B-mode, tissue Doppler
      imaging. CONCLUSION: If valsartan proves effective, it will be an attractive
      measure to improve long term prognosis in aging population and increasing number
      of pacemaker recipients. ClinicalTrials.org (NCT01805804).

PMID- 25858004
TI  - Public key cryptography for quality assurance in randomization for clinical
      trials.

PMID- 25858005
TI  - Behavioural neuroscience: Going on the defensive.

PMID- 25858006
TI  - Neural circuits: Unpredictable turns in the worm.

PMID- 25858007
TI  - Memory: Remembering to forget.

PMID- 25858008
TI  - Cortical plasticity: A critical role for Clock.

PMID- 25858009
TI  - [Association between moderate-severe bronchiolitis and syndrome of inappropriate
      antidiuretic hormone secretion in emergency departments].
AB  - OBJECTIVES: To identify clinical characteristics that may lead to the early
      recognition of patients admitted to the hospital for moderate-to-severe
      bronchiolitis with urine results associated with the syndrome of inappropriate
      antidiuretic hormone secretion (SIADH). PATIENTS AND METHODS: A prospective
      observational study was conducted, spanning the bronchiolitis epidemic season
      (October 2012-March 2013), including all children who were admitted to the
      hospital with a diagnosis of moderate-to-severe bronchiolitis. The following
      criteria were used to establish a diagnosis of SIADH: urine sodium level of 40
      mmol/L or greater, urine osmolarity above 500 mosm/Kg, and urine density of 1020
      g/L or greater. Demographic characteristics, ventilation mode and clinical
      outcome were also analyzed. A comparison was made between those patients that met
      urine SIADH criteria and those who did not. RESULTS: A total of 126 children were
      included, and 23 (18.6%) of them had urine SIADH criteria. Patients in this group
      had a higher incidence of pneumonia and/or atelectasis on chest X-Ray (21.7% vs.
      1.9%, P=.002), worse response to bronchodilator treatment with nebulized
      adrenaline (69,5% vs. 28,1%, P=.016), more need for respiratory assistance (high
      flow oxygen therapy (17.4% vs. 7.7%, p=.016), or non-invasive mechanical
      ventilation (13% vs. 5.8%, P=.034), and more admissions to the PICU (26.1% vs.
      6.8%, P=.007). CONCLUSIONS: Patients older than one month with acute moderate
      bronchiolitis and urine SIADH criteria have worse clinical courses and more need
      for non-invasive mechanical ventilation, PICU admission, and have a higher
      incidence of pneumonia on chest X-ray. For that reason, it is recommended to
      collect a urine sample from these patients to allow an early diagnosis of SIADH,
      and thus early treatment of fluid and electrolyte abnormalities.

PMID- 25858010
TI  - [Prenatal diagnosis of Down syndrome: study of correlations between two types of
      blood collection tubes].
AB  - In the perspective of a future request of accreditation according to the NF EN
      15189 standard of the sector of prenatal diagnosis of the trisomy 21 foetal, we
      compared the results obtained for AFP, hCG, free hCG, PAPP-A and for the risks,
      according to 2 types of blood collection tubes: sterile tube and sterile tube
      with inert gel barrier. For 107 patients, the study of the Passing-Bablok
      regressions between the results from the 2 kinds of tubes, showed perfect
      correlations for measured biochemical markers (AFP, hCG, free hCG and PAPP-A) as
      well as for the estimated risks. A patient who presented a higher risk of foetal
      trisomy 21 (risk at 1/244) for the serum from the sterile tube was not in the
      high-risk area for the serum from the sterile tube with inert gel barrier (risk
      at 1/295). The fact that these 2 values of risk are very close to the threshold
      fixed to 1/250 can probably explain the observed conflict. Working on sterile
      tube, this study confirms that the requests of prenatal diagnosis of the trisomy
      21 foetal taken from tube with inert gel barrier which we receive of outer
      laboratories.

PMID- 25858011
TI  - Sir Harold Delf Gillies, the otolaryngologist and father of modern facial plastic
      surgery: review of his rhinoplasty case notes.
AB  - BACKGROUND: Sir Harold Gillies, born in New Zealand, is widely considered a
      British icon and the father of modern plastic surgery. OBJECTIVE: This article
      provides an overview of his life and the circumstances which led to him laying
      the foundations of plastic surgery in Britain in the early twentieth century.
      METHODS: A hand search and review of case notes from the Gillies Archives at
      Queen Mary's Hospital in Sidcup, UK, where he made history, was conducted.
      RESULTS AND CONCLUSION: Gillies' ongoing legacy was found to also include his
      influence on the development of his cousin Sir Archibald McIndoe's work. Gillies
      was a talented sportsman who engaged in charitable activities. Additionally, he
      was a gifted teacher, with his hospital attracting many young surgeons from
      around the world. He was found to have expressed genius in both the design and
      execution of the art and science of surgery. He incepted reconstructive
      techniques ranging from the world's first gender reassignment operation to facial
      reanimation procedures for the treatment of facial paralysis. His operative work
      on ex-servicemen in need of complex rhinoplasty and in particular the inception
      of the tubed pedicle flap are depicted.

PMID- 25858012
TI  - The development and pilot randomised controlled trial of a group education
      programme for promoting walking in people with intermittent claudication.
AB  - The aim of this study was to develop and pilot a group education programme for
      promoting walking in people with intermittent claudication. Patient focus groups
      (n=24) and literature reviews were conducted to inform the development of the
      education programme, which involves a three-hour group-based education workshop
      and follow-up telephone support. A pilot study was subsequently conducted in
      which 23 new patients (Rutherford category 1-3) were randomly assigned to usual
      care (control) or usual care plus the education programme. Outcomes were assessed
      at baseline and six weeks including daily steps (tri-axial accelerometer),
      walking capacity (six-minute walk test and Gardner treadmill test), and quality
      of life (Intermittent Claudication Questionnaire [ICQ]). Exit interviews were
      conducted to assess the acceptability and usefulness of the programme. Compared
      with controls, the intervention group had superior walking capacity and quality
      of life at six weeks. Mean differences in six-minute walk distance, treadmill
      maximum walking distance and ICQ score were 44.9 m (95% confidence interval [CI],
      6.9 to 82.9), 173 m (95% CI, 23 to 322), and -10.6 (95% CI, -18.9 to -2.3),
      respectively. The daily step count did not differ between groups. The exit
      interviews indicated that participants valued attending the programme, that it
      gave them a greater understanding of their condition, and that they had been
      walking more for exercise since attending. The results suggest that the education
      programme is feasible, acceptable, and potentially useful for improving walking
      capacity and quality of life. A fully-powered trial exploring clinical and cost
      effectiveness is needed. TRIAL REGISTRATION NUMBER: ISRCTN06733130
      (http://www.controlled-trials.com).

PMID- 25858013
TI  - Synthesis and characterization of the new two-dimensional Heisenberg
      antiferromagnet double perovskite BaLaCuSbO6.
AB  - The BaLaCuSbO(6) double perovskite has been successfully synthesized by solid
      state reaction under an air atmosphere. Its structure was refined using powder
      neutron diffraction in the monoclinic space group I2/m with a 4% antisite
      disorder on the B cations. Magnetic measurements give signs of 2D
      antiferromagnetic behaviour with TN around 64 K. The Jahn-Teller distortion
      produced by Cu(2+) ions favours a crystallographic tetragonal distortion and
      consequently the in-plane super-superexchange antiferromagnetic interactions,
      J(90 degrees ), are favoured over the in-plane J(180 degrees ) antiferromagnetic
      exchange interactions. Both, J and J' magnetic interactions have been evaluated
      according to a Heisenberg antiferromagnetic rectangular model using an
      approximation to Curie's law in powers of J/T, being |J| around 10 times stronger
      than |J'|.

PMID- 25858014
TI  - Interdependence of depressive symptoms, school involvement, and academic
      performance between adolescent friends: A dyadic analysis.
AB  - BACKGROUND: Friendships play an important role in the development of school
      involvement and academic performance during adolescence. This study examined the
      interdependence of depressive symptoms, school involvement, and academic
      performance between adolescent same-sex friends. AIMS: Using cross-sectional
      data, we examined whether the link between depressive symptoms and academic
      performance would be mediated by school involvement at the intrapersonal (actor)
      and interpersonal (partner) levels. SAMPLE: Data came from 155 pairs of same-sex
      adolescent friends (80 boys; M(age) = 16.17, SD = 0.44). The actor-partner
      interdependence model was used to examine the dyadic data and mediation
      hypotheses. RESULTS: Mediated actor effects showed that adolescents who had more
      depressive symptoms reported lower academic performance, and such an association
      was mediated by their own and their friend's lower school involvement. Mediated
      partner effects showed that adolescents who had more depressive symptoms also had
      a friend with lower academic performance, and such an association was mediated by
      both individuals' lower school involvement. CONCLUSIONS: This study provided
      evidence to support the broader interpersonal framework for understanding school
      involvement and academic performance. The current findings also have potential
      practical implications, especially for programmes targeted at addressing
      adolescents' school problems.

PMID- 25858015
TI  - Interference of common haemoglobin variants with the Tosoh G7 standard mode HbA1c
      method.
AB  - BACKGROUND: HbA1c methods may be prone to interference by the presence of
      haemoglobin variants. In contrast to the variant mode of the HbA1c method on the
      Tosoh G7 instrument, the literature lacks investigations of haemoglobin variant
      interference with the standard mode. The current study sought to investigate
      whether different haemoglobin variants interfere with the Tosoh G7 standard mode
      HbA1c method, and whether present haemoglobin variants are identifiable on
      respective chromatograms. METHODS: Samples routinely analyzed for HbA1c and
      suspected of having haemoglobin variants (N = 103) were included. HbA1c was
      measured on a Tosoh G7 in standard mode (Tosoh Corporation, Japan), and on the
      DCA Vantage (Siemens, Germany). Haemoglobin variants were identified using the
      VARIANT(TM)beta-Thalassemia Short Program (Bio-Rad Laboratories, Hercules, CA,
      USA) and by DNA sequencing. RESULTS: The Tosoh G7 in standard mode measured
      significantly lower HbA1c results (between 1.0 and 2.5 percentage points absolute
      bias corresponding to between 11 and 27 mmol/mol, p < 0.001) in samples in which
      common haemoglobin variants (HbS, HbC, HbD or HbE) were present (n = 61). No
      significant difference in HbA1c (0.04 percentage points, p = 0.74) was found
      between Tosoh G7 standard mode and DCA Vantage in samples in which haemoglobin
      variants were absent (n = 36). In contrast to HbS and HbD, HbE and HbC trait
      could be identified on respective chromatograms. CONCLUSION: The presence of
      common haemoglobin variants results in falsely low HbA1c measurements on the
      Tosoh G7 in standard mode. HbS and HbD trait are not identifiable on respective
      haemoglobin chromatograms.

PMID- 25858016
TI  - The role of the emergency medical dispatch centre (EMDC) and prehospital
      emergency care safety: results from an incident report (IR) system.
AB  - INTRODUCTION: The role of the emergency medical dispatch centre (EMDC) is
      essential to ensure coordinated and safe prehospital care. The aim of this study
      was to implement an incident report (IR) system in prehospital emergency care
      management with a view to detecting errors occurring in this setting and guiding
      the implementation of safety improvement initiatives. METHODS: An ad hoc IR form
      for the prehospital setting was developed and implemented within the EMDC of
      Verona. The form included six phases (from the emergency call to hospital
      admission) with the relevant list of potential error modes (30 items). This
      descriptive observational study considered the results from 268 consecutive days
      between February and November 2010. RESULTS: During the study period, 161 error
      modes were detected. The majority of these errors occurred in the resource
      allocation and timing phase (34.2%) and in the dispatch phase (31.0%). Most of
      the errors were due to human factors (77.6%), and almost half of them were
      classified as either moderate (27.9%) or severe (19.9%). These results guided the
      implementation of specific corrective actions, such as the adoption of a more
      efficient Medical Priority Dispatch System and the development of educational
      initiatives targeted at both EMDC staff and the population. CONCLUSIONS: Despite
      the intrinsic limits of IR methodology, results suggest how the implementation of
      an IR system dedicated to the emergency prehospital setting can act as a major
      driver for the development of a "learning organization" and improve both efficacy
      and safety of first aid care.

PMID- 25858017
TI  - Knockdown of asparagine synthetase by RNAi suppresses cell growth in human
      melanoma cells and epidermoid carcinoma cells.
AB  - Melanoma, the most aggressive form of skin cancer, causes more than 40,000 deaths
      each year worldwide. And epidermoid carcinoma is another major form of skin
      cancer, which could be studied together with melanoma in several aspects.
      Asparagine synthetase (ASNS) gene encodes an enzyme that catalyzes the glutamine-
      and ATP-dependent conversion of aspartic acid to asparagine, and its expression
      is associated with the chemotherapy resistance and prognosis in several human
      cancers. The present study aims to explore the potential role of ASNS in melanoma
      cells A375 and human epidermoid carcinoma cell line A431. We applied a lentivirus
      mediated RNA interference (RNAi) system to study its function in cell growth of
      both cells. The results revealed that inhibition of ASNS expression by RNAi
      significantly suppressed the growth of melanoma cells and epidermoid carcinoma
      cells, and induced a G0/G1 cell cycle arrest in melanoma cells. Knockdown of ASNS
      in A375 cells remarkably downregulated the expression levels of CDK4, CDK6, and
      Cyclin D1, and upregulated the expression of p21. Therefore, our study provides
      evidence that ASNS may represent a potential therapeutic target for the treatment
      of melanoma. 

PMID- 25858018
TI  - Antidiabetic mechanism of Coptis chinensis polysaccharide through its antioxidant
      property involving the JNK pathway.
AB  - CONTEXT: Antidiabetic activity of Coptis chinensis Franch (Ranunculaceae)
      polysaccharide (CCPW) has been reported. However, its molecular mechanism remains
      unclear. OBJECTIVE: An attempt was made to further verify the antidiabetic
      activity of CCPW on type 2 diabetes mellitus (T2DM) and elucidate the mechanism
      of antidiabetic activity. MATERIALS AND METHODS: Male Wistar rats were fed with
      high-fat diet (HFD) and injected with streptozotocin (STZ) to generate a T2DM
      model. Effects of CCPW on fasting blood glucose (FBG), triglyceride (TG), total
      cholesterol (TC), glutathione (GSH), glutathione peroxidases (GSH-Px), superoxide
      dismutases (SOD), catalase (CAT), malondialdehyde (MDA), c-jun n-terminal kinase
      (JNK), phosphorylated insulin receptor substrate 1 (phospho-IRS1), phosphorylated
      phosphatidylinositol 3 kinase (phospho-PI3Kp85) and glucose transporter 4 (Glut4)
      were investigated. RESULTS: FBG level of diabetic rats could be significantly
      inhibited by 51.2, 42.7, and 23.3% through administration of CCPW at doses of
      200, 100, and 50 mg/kg b.w., respectively (p < 0.01). CCPW also could
      significantly reduce TG by 19.2, 12.1, and 7.4%, and TC by 24.2, 20.9, and 18.7%,
      respectively (p < 0.05 or p < 0.01). CCPW showed an obvious antioxidant effect
      through increasing GSH-Px, SOD, and CAT activities, and decreasing GSH and MDA
      contents (p < 0.05 or p < 0.01). Furthermore, CCPW could inhibit JNK and phospho
      IRS1 expression and promote the expression of phospho-PI3Kp85 and Glut4 compared
      with those in the DM group (p < 0.05 or p < 0.01). DISCUSSION AND CONCLUSION:
      CCPW can produce antidiabetic activity in rats with T2DM through its
      antioxidative effect, which is closely related to the JNK/IRS1/PI3K pathway.

PMID- 25858019
TI  - The Downsides of Extreme Conscientiousness for Psychological Well-being: The Role
      of Obsessive Compulsive Tendencies.
AB  - Although conscientiousness exhibits positive relations with psychological well
      being, theoretical and empirical work suggests individuals can be too
      conscientious, resulting in obsessive-compulsiveness, and therein less positive
      individual outcomes. However, the potential for curvilinearity between
      conscientiousness and well-being has been underexplored. We measured 912 subjects
      on facets of conscientiousness, obsessive-compulsive personality, and well-being
      variables (life satisfaction, job satisfaction, self-esteem, positive affect,
      negative affect, work stress). Methods of scoring included traditional sum
      scoring, traditional item response theory (IRT), and a relatively new IRT
      approach. Structural models were estimated to evaluate curvilinearity. Results
      confirmed the curvilinear relationship between conscientiousness and well-being,
      and demonstrated that differential facet-level relationships underlie weaker
      curvilinearity at the general trait level. Consistency was found in the strength
      of relation between conscientiousness facets with their obsessive-compulsive
      variants and their contribution to decreased well-being. The most common
      association was that higher standing on conscientiousness facets was positively
      related to negative affect. Findings support the idea that extreme standing on
      facets of conscientiousness more strongly linked to their obsessive-compulsive
      variants contributed to lower well-being, highlighting the importance of
      considering alternative functional representations of the relationship between
      personality and other constructs. Future work should seek to further clarify the
      link between conscientiousness and negative affect.

PMID- 25858020
TI  - High Local Concentrations of Intradermal MSCs Restore Skin Integrity and
      Facilitate Wound Healing in Dystrophic Epidermolysis Bullosa.
AB  - Dystrophic epidermolysis bullosa (DEB) is an incurable skin fragility disorder
      caused by mutations in the COL7A1 gene, coding for the anchoring fibril protein
      collagen VII (C7). Life-long mechanosensitivity of skin and mucosal surfaces is
      associated with large body surface erosions, chronic wounds, and secondary
      fibrosis that severely impede functionality. Here, we present the first
      systematic long-term evaluation of the therapeutic potential of a mesenchymal
      stromal cell (MSC)-based therapy for DEB. Intradermal administration of MSCs in a
      DEB mouse model resulted in production and deposition of C7 at the dermal
      epidermal junction, the physiological site of function. The effect was dose
      dependent with MSCs being up to 10-fold more potent than dermal fibroblasts. MSCs
      promoted regeneration of DEB wounds via normalization of dermal and epidermal
      healing and improved skin integrity through de novo formation of functional
      immature anchoring fibrils. Additional benefits were gained by MSCs' anti
      inflammatory effects, which led to decreased immune cell infiltration into
      injured DEB skin. In our setting, the clinical benefit of MSC injections lasted
      for more than 3 months. We conclude that MSCs are viable options for localized
      DEB therapy. Importantly, however, the cell number needed to achieve therapeutic
      efficacy excludes the use of systemic administration. 

PMID- 25858021
TI  - The effect of chemotherapy on optic pathway gliomas and their sub-components: A
      volumetric MR analysis study.
AB  - BACKGROUND: Optic pathway gliomas (OPG) represent 5% of pediatric brain tumors
      and compose a major therapeutic dilemma to the treating physicians. While
      chemotherapy is widely used for these tumors, our ability to predict radiological
      response is still lacking. In this study, we use volumetric imaging to examine in
      detail the long-term effect of chemotherapy on the tumor as well as its various
      sub-components. PROCEDURE: The tumors of 15 patients with OPG, treated with
      chemotherapy, were longitudinally measured using our novel, previously described
      volumetric method. Patients were treated with up to five lines of chemotherapy.
      Sufficient follow-up imaging data, and patient's numbers, allowed for analysis of
      two treatment lines. Volumetric measurements of the tumors were segmented into
      solid-non-enhancing, solid-enhancing, and cystic components. Outcome analysis was
      done per specific treatment line and for the overall follow-up period. RESULTS:
      An average reduction of 9.7% (+/-23%) in the gross-total-solid volume (GTSV) was
      noted following treatment with vincristine and carboplatin. The cystic component
      grew under therapy by an average of 12.6% (+/-39%). When measured over the course
      of the whole study period, the cystic component grew by an average of 35% (+/
      100%) and the GTSV increased by 12% (+/-35%). CONCLUSION: Initial treatment with
      vincristine and carboplatin seems to have a minimal initial effect, mostly on the
      solid components. The cystic component in itself seems to be unaffected by
      chemotherapy, and contributes to the subsequent growth of the total volume.
      During the overall treatment period, both solid and cystic components grew
      regardless of combined treatment methods.

PMID- 25858022
TI  - Effect of alteration of caveolin-1 expression on doxorubicin-induced apoptosis in
      H9c2 cardiac cells.
AB  - Doxorubicin is an anthracycline antibiotic widely used in cancer treatment.
      Although its antitumor efficacy appears to be dose dependent, its clinical use is
      greatly restricted by the development of cardiotoxicity associated with
      apoptosis. Although caveolin-1, the major structural protein in caveolae, can
      positively or negatively regulate apoptosis depending on the stimulus or cell
      types, the contribution of caveolin-1 to doxorubicin-induced apoptosis remains
      unknown. This study was performed to identify the regulatory role of caveolin-1
      on doxorubicin-induced apoptosis in H9c2 cardiac cells using a genetic approach.
      Caveolin-1 knockdown with a short hairpin (sh) RNA adenovirus, but not
      overexpression of wild-type caveolin-1, resulted in a marked inhibition of
      doxorubicin-induced caspase-3 cleavage. However, caveolin-1 knockdown tended to
      protect against doxorubicin-induced decrease in cell viability, but it did not
      significantly reverse cell death induced by doxorubicin. Doxorubicin stimulated
      the phosphorylation of p38 and extracellular signal regulated kinase (ERK).
      Doxorubicin-induced caspase-3 cleavage was inhibited by U0126, a MEK inhibitor or
      SB203580, a p38 inhibitor. Caveolin-1 knockdown markedly inhibited doxorubicin
      induced p-38 phosphorylation but not ERK-mediated p-53 phosphorylation in H9c2
      cardiac cells. Our results suggest that reduced caveolin-1 expression plays an
      anti-apoptotic role in doxorubicin-induced apoptosis but that it is insufficient
      to prevent such an apoptosis in H9c2 cardiac cells. 

PMID- 25858023
TI  - Effect of NMDAR antagonists in the tetrabenazine test for antidepressants:
      comparison with the tail suspension test.
AB  - OBJECTIVE: The N-methyl-d-aspartate receptor (NMDAR) antagonist ketamine,
      produces rapid and enduring antidepressant effect in patients with treatment
      resistant depression. Similar dramatic effects have not been observed in clinical
      trials with other NMDAR antagonists indicating ketamine may possess unique
      pharmacological properties. Tetrabenazine induces ptosis (a drooping of the
      eyelids), and the reversal of this effect, attributed to a sympathomimetic
      action, has been used to detect first-generation antidepressants, as well as
      ketamine. Because the actions of other NMDAR antagonists have not been reported
      in this measure, we examined whether reversal of tetrabenazine-induced ptosis was
      unique to ketamine, or a class effect of NMDAR antagonists. METHODS: The effects
      of ketamine and other NMDAR antagonists to reverse tetrabenazine-induced ptosis
      were examined and compared with their antidepressant-like effects in the tail
      suspension test (TST) in mice. RESULTS: All the NMDAR antagonists tested produced
      a partial reversal of tetrabenazine-induced ptosis and, as expected, reduced
      immobility in the TST. Ketamine, memantine, MK-801 and AZD6765 were all about
      half as potent in reversing tetrabenazine-induced ptosis compared to reducing
      immobility in the TST, while an NR2B antagonist (Ro 25-6981) and a glycine
      partial agonist (ACPC) were equipotent in both tests. CONCLUSION: The ability to
      reverse tetrabenazine-induced ptosis is a class effect of NMDAR antagonists.
      These findings are consistent with the hypothesis that the inability of
      memantine, AZD6765 (lanicemine) and MK-0657 to reproduce the rapid and robust
      antidepressant effects of ketamine in the clinic result from insufficient dosing
      rather than a difference in mechanism of action among these NMDAR antagonists.

PMID- 25858024
TI  - Resistance to normal human serum reveals Trypanosoma lewisi as an underestimated
      human pathogen.
AB  - Human-infectious trypanosomes such as Trypanosoma cruzi, T. brucei rhodesiense,
      and T. b. gambiense can be discriminated from those only infecting animals by
      their resistance to normal human serum (NHS). These parasites are naturally
      resistant to trypanolysis induced by the human-specific pore-forming serum
      protein apolipoprotein L1 (ApoL-1). T. lewisi, a worldwide distributed parasite,
      has been considered as rat-specific and non-pathogenic to the natural hosts. Here
      we provide evidence that 19 tested T. lewisi isolates from Thailand and China
      share resistance to NHS. Further investigation on one selected isolate CPO02
      showed that it could resist at least 90% NHS or 30 MUg/ml recombinant human ApoL
      1 (rhApoL-1) in vitro, in contrast to T. b. brucei which could not survive in
      0.0001% NHS and 0.1 MUg/ml rhApoL-1. In vivo tests in rats also demonstrated that
      this parasite is fully resistant to lysis by NHS. Together with recent reports of
      atypical human infection by T. lewisi, these data allow the conclusion that T.
      lewisi is potentially an underestimated and thus a neglected human pathogen.

PMID- 25858025
TI  - The World Health Organization and global health estimates: improving
      collaboration and capacity.
AB  - Global, regional, and country statistics on population and health indicators are
      important for assessing development and health progress and for guiding resource
      allocation; however, data are often lacking, especially in low- and middle-income
      countries. To fill the gaps, statistical modelling is frequently used to produce
      comparable health statistics across countries that can be combined to produce
      regional and global statistics. The World Health Organization (WHO), in
      collaboration with other United Nations agencies and academic experts, regularly
      updates estimates for key indicators and involves its Member States in the
      process. Academic institutions also publish estimates independent from the WHO
      using different methods. The use of sophisticated statistical estimation methods
      to fill missing values for countries can reduce the pressures on governments and
      development agencies to improve information systems. Efforts to improve estimates
      must be accompanied by concerted attempts to address data gaps, common standards
      for documentation, sharing of data and methods, and regular interaction and
      collaboration among all groups involved. 

PMID- 25858027
TI  - Time-lag effects of global vegetation responses to climate change.
AB  - Climate conditions significantly affect vegetation growth in terrestrial
      ecosystems. Due to the spatial heterogeneity of ecosystems, the vegetation
      responses to climate vary considerably with the diverse spatial patterns and the
      time-lag effects, which are the most important mechanism of climate-vegetation
      interactive effects. Extensive studies focused on large-scale vegetation-climate
      interactions use the simultaneous meteorological and vegetation indicators to
      develop models; however, the time-lag effects are less considered, which tends to
      increase uncertainty. In this study, we aim to quantitatively determine the time
      lag effects of global vegetation responses to different climatic factors using
      the GIMMS3g NDVI time series and the CRU temperature, precipitation, and solar
      radiation datasets. First, this study analyzed the time-lag effects of global
      vegetation responses to different climatic factors. Then, a multiple linear
      regression model and partial correlation model were established to statistically
      analyze the roles of different climatic factors on vegetation responses, from
      which the primary climate-driving factors for different vegetation types were
      determined. The results showed that (i) both the time-lag effects of the
      vegetation responses and the major climate-driving factors that significantly
      affect vegetation growth varied significantly at the global scale, which was
      related to the diverse vegetation and climate characteristics; (ii) regarding the
      time-lag effects, the climatic factors explained 64% variation of the global
      vegetation growth, which was 11% relatively higher than the model ignoring the
      time-lag effects; (iii) for the area with a significant change trend (for the
      period 1982-2008) in the global GIMMS3g NDVI (P < 0.05), the primary driving
      factor was temperature; and (iv) at the regional scale, the variation in
      vegetation growth was also related to human activities and natural disturbances.
      Considering the time-lag effects is quite important for better predicting and
      evaluating the vegetation dynamics under the background of global climate change.

PMID- 25858026
TI  - A highly selective fluorescent sensor for glucosamine.
AB  - A new fluorescent chemical sensor for glucosamine is reported. The sensor is
      based on a boronic acid-containing coumarin aldehyde and shows excellent
      selectivity for glucosamine by forming a boronic ester with the sugar diol as
      well as an iminium ion with the amine group of glucosamine. The sensor
      successfully discriminates glucosamine over other similar biomolecules in terms
      of both fluorescence intensity and binding affinity. This method provides a new
      concept for the design and synthesis of very selective turn-on optical sensors
      for selective detection of multi-functional biomolecules. 

PMID- 25858028
TI  - Emergence of colistin resistance without loss of fitness and virulence after
      prolonged colistin administration in a patient with extensively drug-resistant
      Acinetobacter baumannii.
AB  - The spread of extensively drug-resistant (XDR) gram-negative bacteria has boosted
      colistin use, with a resultant selection of colistin-resistant, often pandrug
      resistant strains. Whether acquisition of further resistance mechanisms
      translates into a reduced virulence is the subject of active research. In this
      report, we describe clinical features of an immunocompromised patient who
      developed infection due to colistin-resistant Acinetobacter baumannii while on
      long-term colistin therapy. We analyzed phenotypic and genotypic characteristics,
      molecular mechanisms of colistin resistance, and in vitro and in vivo fitness of
      sequential colistin-sensitive and colistin-resistant strains isolated from the
      patient. Both colistin-sensitive and colistin-resistant strains were XDR and
      showed identical ST78 genotype. At variance with prior reports on colistin
      resistant strains of A. baumannii, resistance to colistin due to P233S mutation
      in PmrB sensor kinase did not associate with any measurable reduction in strain
      fitness, growth characteristics, and virulence. 

PMID- 25858029
TI  - The immune signaling pathways of Manduca sexta.
AB  - Signal transduction pathways and their coordination are critically important for
      proper functioning of animal immune systems. Our knowledge of the constituents of
      the intracellular signaling network in insects mainly comes from genetic analyses
      in Drosophila melanogaster. To facilitate future studies of similar systems in
      the tobacco hornworm and other lepidopteran insects, we have identified and
      examined the homologous genes in the genome of Manduca sexta. Based on 1:1
      orthologous relationships in most cases, we hypothesize that the Toll, Imd, MAPK
      JNK-p38 and JAK-STAT pathways are intact and operative in this species, as are
      most of the regulatory mechanisms. Similarly, cellular processes such as
      autophagy, apoptosis and RNA interference probably function in similar ways,
      because their mediators and modulators are mostly conserved in this lepidopteran
      species. We have annotated a total of 186 genes encoding 199 proteins, studied
      their domain structures and evolution, and examined their mRNA levels in tissues
      at different life stages. Such information provides a genomic perspective of the
      intricate signaling system in a non-drosophiline insect. 

PMID- 25858030
TI  - Crosstalk between the renal sympathetic nerve and intrarenal angiotensin II
      modulates proximal tubular sodium reabsorption.
AB  - NEW FINDINGS: What is the topic of this review? The sympathetic control of renal
      sodium tubular reabsorption is dependent on activation of the intrarenal renin
      angiotensin system and activation of the angiotensin II type 1 (AT1 ) receptor by
      angiotensin II. What advances does it highlight? Despite the fact that the
      interaction between the sympathetic nervous system and angiotensin II regarding
      salt reabsorption is a well-known classical mechanism for the maintenance of
      extracellular volume homeostasis, the underlying molecular signalling is not
      clearly understood. It has been shown recently that renal nerve stimulation
      increases intrarenal angiotensin II and activates the AT1 receptor, triggering a
      signalling cascade that leads to elevations of Na(+) -H(+) exchanger isoform 3
      mediated tubular transport. In this short review, the crosstalk between
      intrarenal angiotensin II and renal nerve activity and its effect on sodium
      reabsorption is addressed. In this review, we address the importance of the
      interaction between the sympathetic nervous system and intrarenal renin
      angiotensin system in modulating renal tubular handling of sodium and water. We
      have recently shown that increased Na(+) -H(+) exchanger isoform 3 (NHE3)
      activity induced by renal nerve stimulation (RNS) depends on the activation of
      the angiotensin II type 1 (AT1 ) receptor by angiotensin II (Ang II). Low
      frequency RNS resulted in higher levels of intrarenal angiotensinogen and Ang II
      independent of changes in blood pressure, the glomerular filtration rate and
      systemic angiotensinogen. Angiotensin II, via the AT1 receptor, triggered an
      intracellular pathway activating NHE3 in the renal cortex, leading to
      antinatriuresis and antidiuresis. Pharmacological blockade of the AT1 receptor
      with losartan prior to RNS abolished both the functional and the molecular
      responses, suggesting that intrarenal Ang II acting via the AT1 receptor is a
      major factor for NHE3-mediated sodium and water reabsorption induced by RNS.

PMID- 25858031
TI  - Information Needs of Family Caregivers of People With Dementia.
AB  - PURPOSE: Understanding caregiver needs is essential when caring for people with
      dementia. The aim of this study was to identify family caregivers' information
      needs as perceived by home care workers and the caregivers themselves. DESIGN:
      This study used a descriptive survey design and convenience sampling. METHODS:
      The two groups of care providers were given a list of 48 items and asked to
      choose caregivers' top 10 information needs. FINDINGS: Group 1 (n = 33 unpaid
      family caregivers) identified dealing with behavior changes and group 2 (n = 59
      paid home care workers) identified providing personal care as most important.
      CONCLUSION: While differences between these groups emerged, both care providers
      chose more items related to needing help for the care recipient, than items
      related to needing help for the caregivers themselves, e.g., support group.
      CLINICAL RELEVANCE: These information needs can be used by rehabilitation nurses
      and other healthcare professionals to develop educational materials and
      supportive interventions.

PMID- 25858033
TI  - Burst Spinal Cord Stimulation in a Patient with Complex Regional Pain Syndrome: A
      2-year Follow-Up.
AB  - Spinal cord stimulation (SCS) is an effective therapy to treat most patients with
      complex regional pain syndrome (CRPS); however, the effect is not always
      maintained over time. We present a case report of a patient successfully treated
      with burst SCS after a diminishing effect of conventional tonic stimulation.
      Burst stimulation is a novel method of SCS consisting of delivering 5 spikes at
      500 Hz, 40 times/s (pulse width 1 mseconds). The current output is set to a
      subthreshold level for paresthesia in the supine position. REPORT OF A CASE: A 65
      year-old woman with CRPS in the left upper extremity experienced a diminishing
      effect of conventional tonic SCS over time, resulting in an increase of pain with
      a mean Numerical Rating Score (NRS) of 8. After treatment with burst SCS, the NRS
      declined to 2 and remained at that level for 2 years. An intermediate/brief
      period, due to increased CRPS activity, resulted in a higher pain score, which
      was successfully managed by increasing the burst stimulation to a higher level of
      subthreshold stimulation. DISCUSSION: In this patient with CRPS, burst SCS was
      successful in reducing pain scores that could no longer be achieved with
      conventional tonic stimulation. It appears that pain reduction with burst SCS can
      be sustained for a relatively long period of time.

PMID- 25858034
TI  - Regioselective sulfamoylation at low temperature enables concise syntheses of
      putative small molecule inhibitors of sulfatases.
AB  - Regioselective sulfamoylation of primary hydroxyl groups enabled a 5-step
      synthesis (overall yield 17%) of the first reported small molecule inhibitor of
      sulfatase-1 and 2, ((2S,3R,4R,5S,6R)-4,5-dihydroxy-2-methoxy-6
      ((sulfamoyloxy)methyl)tetrahydro-2H-pyran-3-yl)sulfamic acid, which obviated the
      use of hydroxyl protecting groups and is a marked improvement on the reported 9
      step synthesis (overall yield 9%) employing hazardous trifluoromethylsulfonyl
      azide. The sulfamoylation methodology was used to prepare a range of derivatives
      of 1, and inhibition data was generated for Sulf-2, ARSA and ARSB.

PMID- 25858032
TI  - GRP78/Dna K Is a Target for Nexavar/Stivarga/Votrient in the Treatment of Human
      Malignancies, Viral Infections and Bacterial Diseases.
AB  - Prior tumor cell studies have shown that the drugs sorafenib (Nexavar) and
      regorafenib (Stivarga) reduce expression of the chaperone GRP78.
      Sorafenib/regorafenib and the multi-kinase inhibitor pazopanib (Votrient)
      interacted with sildenafil (Viagra) to further rapidly reduce GRP78 levels in
      eukaryotes and as single agents to reduce Dna K levels in prokaryotes. Similar
      data were obtained in tumor cells in vitro and in drug-treated mice for: HSP70,
      mitochondrial HSP70, HSP60, HSP56, HSP40, HSP10, and cyclophilin A. Prolonged
      'rafenib/sildenafil treatment killed tumor cells and also rapidly decreased the
      expression of: the drug efflux pumps ABCB1 and ABCG2; and NPC1 and NTCP,
      receptors for Ebola/Hepatitis A and B viruses, respectively. Pre-treatment with
      the 'Rafenib/sildenafil combination reduced expression of the Coxsackie and
      Adenovirus receptor in parallel with it also reducing the ability of a serotype 5
      Adenovirus or Coxsackie virus B4 to infect and to reproduce. Sorafenib/pazopanib
      and sildenafil was much more potent than sorafenib/pazopanib as single agents at
      preventing Adenovirus, Mumps, Chikungunya, Dengue, Rabies, West Nile, Yellow
      Fever, and Enterovirus 71 infection and reproduction. 'Rafenib drugs/pazopanib as
      single agents killed laboratory generated antibiotic resistant E. coli which was
      associated with reduced Dna K and Rec A expression. Marginally toxic doses of
      'Rafenib drugs/pazopanib restored antibiotic sensitivity in pan-antibiotic
      resistant bacteria including multiple strains of blakpc Klebsiella pneumoniae.
      Thus, Dna K is an antibiotic target for sorafenib, and inhibition of GRP78/Dna K
      has therapeutic utility for cancer and for bacterial and viral infections.

PMID- 25858035
TI  - Two-year impact of lifestyle changes on workplace productivity loss in the Heart
      of New Ulm Project.
AB  - OBJECTIVE: Unhealthy lifestyles have been associated with lower workplace
      productivity and are the main targets of worksite wellness programmes. The degree
      to which workplace productivity increases over time in response to changes in
      lifestyle habits, however, remains unclear. The purpose of this study was to
      examine the association between 2-year changes in key lifestyle risk factors and
      workplace productivity loss. METHOD: A retrospective cohort of 1273 employed
      adults in 2009 and 2011 was studied from the Heart of New Ulm Project. The
      outcome was overall workplace productivity loss in 2011. Predictors included 2
      year changes in smoking, alcohol use, fruit/vegetable consumption and physical
      activity, as well as an optimal lifestyle score based on a composite of these
      four factors. RESULTS: The adjusted model indicated that participants who
      continued to smoke over 2 years had significantly greater overall workplace
      productivity loss compared to those who remained non-smokers during the same
      timeframe (9.8% vs 2.5% productivity loss, p=0.031). Lifestyle improvements,
      however, were not associated with a reduction in workplace productivity loss.
      CONCLUSIONS: Employed adults in this cohort who quit smoking, moderated alcohol
      use, increased fruit/vegetable consumption, or increased physical activity over 2
      years did not have less productivity loss compared to those whose lifestyle
      factors remained stable. In workforces where productivity is already high and/or
      lifestyle factors are generally healthy, further lifestyle improvements may have
      limited impact on employee productivity. Larger experimental studies in more
      diverse regions are needed to help guide employers' investments in lifestyle
      oriented worksite wellness programmes.

PMID- 25858036
TI  - Mental health nurses can increase capability and capacity in primary care by
      educating practice nurses: an evaluation of an education programme in England.
AB  - Most people with a mental health problem in England are cared for by clinicians
      in primary care who may have had little or no training in this area. Our aim was
      to develop an accessible education programme which was appropriate to the
      learning needs of this workforce. A survey of the mental health and well-being
      training needs and preferred learning methods of practice nurses was undertaken,
      then a programme of education was developed by a primary care mental health
      expert. Teaching was delivered by mental health nurses who were trained as
      educators. Both the practice nurses and mental health nurses felt their clinical
      practice would improve as a result of being involved in this programme. To
      sustain the learning, mental health nurses were supported by attending and then
      leading their own action learning sets. This model of education can be adapted
      and used by health organizations both nationally and internationally. Research is
      required to find out whether training practice nurses using this programme has an
      impact on patients.

PMID- 25858038
TI  - Magnetic resonance imaging in movement disorders.

PMID- 25858037
TI  - A Perspective on the Impact of the Shine-Through Artifact in Clinical
      Applications of PET/MR Imaging.

PMID- 25858039
TI  - 18F-FLT PET Evaluation of Radiation Response.

PMID- 25858040
TI  - The role of radionuclide imaging in the surgical management of primary
      hyperparathyroidism.
AB  - Primary hyperparathyroidism is a frequent and potentially debilitating endocrine
      disorder for which surgery is the only curative treatment. The modalities of
      parathyroid surgery have changed over the last 2 decades, as conventional
      bilateral neck exploration is no longer the only surgical approach. Parathyroid
      scintigraphy plays a major role in defining the surgical strategy, given its
      ability to orient a targeted (focused) parathyroidectomy and to recognize ectopic
      locations or multiglandular disease. This review, which represents a
      collaborative effort between nuclear physicians, endocrinologists, and endocrine
      surgeons, emphasizes the importance of performing imaging before any surgery for
      primary hyperparathyroidism, even in the case of conventional bilateral neck
      exploration. We discuss the advantages and drawbacks of targeted
      parathyroidectomy and the performance of various scintigraphic protocols to guide
      limited surgery. We also discuss the optimal strategy to localize the offending
      gland before reoperation for persistent or recurrent hyperparathyroidism.
      Finally, we describe the potential applications of novel PET tracers, with
      special emphasis on (18)F-fluorocholine. 

PMID- 25858041
TI  - 99mTc SPECT/CT Versus Planar Lymphoscintigraphy for Preoperative Sentinel Lymph
      Node Detection in Cervical Cancer: A Systematic Review and Metaanalysis.
AB  - We aimed to compare SPECT/CT and lymphoscintigraphy on overall and bilateral
      sentinel lymph node (SLN) detection in cervical cancer patients. METHODS: A
      systematic search was performed on August 1, 2014, in PubMed, Embase, Scopus, and
      the Cochrane library. The syntax was based on synonyms of the terms cervical
      cancer, SPECT/CT, and lymphoscintigraphy. Retrieved articles were screened on
      their title/abstract and considered eligible when an SLN procedure was performed
      using both imaging modalities and if detection results were reported. Two
      independent reviewers assessed all included studies on methodologic quality using
      QUADAS-2. Studies were pooled on their odds ratios (ORs) with a random-effects
      model. RESULTS: The search yielded 962 unique articles, of which 8 were
      ultimately included. The studies were recent retrospective or prospective cohort
      studies of limited size (n = 7-51) but sufficient methodologic quality. The
      median overall detection (>=1 SLN in a patient) was 98.6% for SPECT/CT (range,
      92.2%-100.0%) and 85.3% for lymphoscintigraphy (range, 70.0%-100.0%). This
      corresponded to a pooled overall SLN detection OR of 2.5 (95% CI, 1.2-5.3) in
      favor of SPECT/CT. The reported median bilateral detection (>=1 SLN in each
      hemipelvis) was 69.0% for SPECT/CT (range, 62.7%-79.3%) and 66.7% for
      lymphoscintigraphy (range, 56.9%-75.8%), yielding a pooled OR of 1.2 (95% CI, 0.7
      2.1). No significant difference in the number of visualized SLNs was observed at
      a pooled ratio of 1.2 (95% CI, 0.9-1.6). CONCLUSION: In cervical cancer patients,
      preoperative SLN imaging with SPECT/CT results in superior overall SLN detection
      in comparison with planar lymphoscintigraphy.

PMID- 25858042
TI  - Assessment of Simplified Blood Dose Protocols for the Estimation of the Maximum
      Tolerable Activity in Thyroid Cancer Patients Undergoing Radioiodine Therapy
      Using 124I.
AB  - In high-activity radioiodine therapies for differentiated thyroid cancer, blood
      dosimetry has been developed to estimate the maximum tolerable activity (MTA) of
      (131)I that can be safely administered without leading to toxic effects. The
      reference protocol involves a series of both blood sampling (BS) and whole-body
      counting (WC) over a period of several days. The aim of this retrospective study
      was to identify simplified protocols without an appreciable loss of accuracy.
      METHODS: Data from 211 thyroid cancer patients who received (124)I blood
      dosimetries were retrospectively analyzed. BS and WC acquired at approximately 1
      2, 4, 24, 48, and 96 h or longer after (124)I administration were included. This
      dataset was used to determine the reference MTA and estimations based on a
      reduced number of combined data from BS and respective WC. MTA estimates were
      also determined on the basis of either BS or WC alone using some simplifying
      assumptions in the dosimetry approach. A simplified protocol was considered
      equivalent to the reference protocol if the estimates of 95% of the MTAs were
      within the +/-20% range and the absolute maximum percentage deviation did not
      exceed the limit of 30% in a few cases. Lin's concordance correlation analysis
      was applied to assess the protocol's agreements. RESULTS: Two equivalent
      protocols were identified that included both BS and respective WC acquired at
      only 3 time points (1-2, 24 or 48, and >=96 h). Further equivalent protocols with
      only 3 blood samples drawn at similar time points were discovered for patients,
      who had undergone at least 1 radioiodine therapy. For all equivalent protocols,
      deviations of the mean absolute percentage MTA were below 9% and Lin's
      concordance correlation coefficients of 0.95 or greater were found, indicating
      almost excellent agreement (according to Partik's criteria). CONCLUSION: The
      pretherapy blood dosimetry protocol can be substantially shortened and may be
      beneficial to patients and patient management while reducing the radiation
      exposure to medical staff.

PMID- 25858043
TI  - Clinical Assessment of Emission- and Segmentation-Based MR-Guided Attenuation
      Correction in Whole-Body Time-of-Flight PET/MR Imaging.
AB  - The joint maximum-likelihood reconstruction of activity and attenuation (MLAA)
      for emission-based attenuation correction has regained attention since the advent
      of time-of-flight PET/MR imaging. Recently, we improved the performance of the
      MLAA algorithm using an MR imaging-constrained gaussian mixture model (GMM). In
      this study, we compare the performance of our proposed algorithm with standard 4
      class MR-based attenuation correction (MRAC) implemented on commercial systems.
      METHODS: Five head and neck (18)F-FDG patients were scanned on PET/MR imaging and
      PET/CT scanners. Dixon fat and water MR images were registered to CT images. MRAC
      maps were derived by segmenting the MR images into 4 tissue classes and assigning
      predefined attenuation coefficients. For MLAA-GMM, MR images were segmented into
      known tissue classes, including fat, soft tissue, lung, background air, and an
      unknown MR low-intensity class encompassing cortical bones, air cavities, and
      metal artifacts. A coregistered bone probability map was also included in the
      unknown tissue class. Finally, the GMM prior was constrained over known tissue
      classes of attenuation maps using unimodal gaussians parameterized over a patient
      population. RESULTS: The results showed that the MLAA-GMM algorithm outperformed
      the MRAC method by differentiating bones from air gaps and providing more
      accurate patient-specific attenuation coefficients of soft tissue and lungs. It
      was found that the MRAC and MLAA-GMM methods resulted in average standardized
      uptake value errors of -5.4% and -3.5% in the lungs, -7.4% and -5.0% in soft
      tissues/lesions, and -18.4% and -10.2% in bones, respectively. CONCLUSION: The
      proposed MLAA algorithm is promising for accurate derivation of attenuation maps
      on time-of-flight PET/MR systems.

PMID- 25858044
TI  - Immuno-PET and Immuno-SPECT of Rheumatoid Arthritis with Radiolabeled Anti
      Fibroblast Activation Protein Antibody Correlates with Severity of Arthritis.
AB  - One of the most prominent cell populations playing a role in rheumatoid arthritis
      (RA) is activated fibroblast-like synoviocytes. Among many other proteins,
      fibroblast-like synoviocytes dominantly express fibroblast activation protein
      (FAP). Because of the high expression of FAP in arthritic joints,
      radioimmunoimaging of activated fibroblasts with anti-FAP antibodies might be an
      attractive noninvasive imaging tool in RA. METHODS: SPECT and PET with (111)In-
      and (89)Zr-labeled anti-FAP antibody 28H1 was performed in mice with CIA. The
      radioactivity uptake in joints was quantified and correlated with arthritis
      score. RESULTS: Both (111)In-28H1 and (89)Zr-28H1 showed high uptake in inflamed
      joints, being 3-fold higher than that of the irrelevant isotype-matched control
      antibody DP47GS, clearly indicating specific accumulation of 28H1. Uptake of
      (111)In-28H1 ranged from 2.2 percentage injected dose per gram (%ID/g) in
      noninflamed joints to 32.1 %ID/g in severely inflamed joints. DP47GS accumulation
      ranged from 1.6 %ID/g in noninflamed tissue to 12.0 %ID/g in severely inflamed
      joints. Uptake of 28H1 in inflamed joints correlated with arthritis score
      (Spearman rho, 0.69; P < 0.0001) and increased with severity of arthritis.
      CONCLUSION: SPECT/CT imaging with the anti-FAP antibody (111)In-28H1 specifically
      visualized arthritic joints with high resolution, and tracer accumulation
      correlated with the severity of the inflammation in murine experimental
      arthritis. Background uptake of the radiolabeled antibody was low, resulting in
      excellent image quality. (89)Zr-28H1 was less favorable for RA imaging because of
      an elevated bone uptake of (89)Zr. Future studies will focus on the potential
      role of 28H1 as a tool to monitor therapy response early on.

PMID- 25858045
TI  - A Phase I-II, Open-Label, Multicenter Trial to Determine the Dosimetry and Safety
      of 99mTc-Sestamibi in Pediatric Subjects.
AB  - Myocardial perfusion imaging has long been used off label by practitioners
      attending for children with cardiac aliments. To provide clinicians with evidence
      based dosage recommendation, a phase I-II, open-label, nonrandomized, multicenter
      trial was therefore designed using (99m)Tc-sestamibi in pediatric subjects
      (registered under www.clinicaltrials.gov identifier no. NCT00162045). METHODS:
      Safety and pharmacokinetic data were collected from 78 subjects using either a 1
      d imaging protocol (3.7-7.4 MBq/kg, followed by 11.1 MBq/kg) or a 2-d protocol
      (7.4 MBq/kg for both rest and stress). Anterior and posterior planar images were
      collected at 15 min, 1.5 h, 4 h, and 8 h. Blood and urine samples were collected
      at predetermined times. RESULTS: Subjects included 39 children (mean age +/- SD,
      8.5 +/- 2.04 y) and 39 adolescents (mean age +/- SD, 13.6 +/- 1.39 y). Mean
      estimated organ-absorbed doses to the upper large intestine, small intestine,
      gallbladder wall, and lower large intestines were 0.082, 0.043, 0.042, and 0.035
      mSv/MBq, respectively. All patients tolerated the radiotracer without serious
      adverse effects. Significant differences were observed in the liver, upper large
      intestine contents, and small intestine contents between rest and stress imaging.
      The effective dose equivalent and effective dose averages were lower in
      adolescents than younger children (0.011 and 0.019 mSv/MBq, respectively; P <
      0.0001). Percentage injected doses (%IDs) corrected for radioactive decay in all
      dosimetry-evaluable subjects at 15 min and 4 h were 1.9% and 1.2% in the
      myocardium. Similarly in the lungs, the %ID for all dosimetry-evaluable subjects
      was 4.9% at 15 min after injection. At rest, the %ID in the liver decreased from
      a maximum of about 26% at 15 min to less than 9% at 90 min. With stress, values
      decreased from 15% to 7%, respectively. CONCLUSION: The estimates of radiation
      dosimetry, pharmacokinetic parameters, and safety profile in this study
      population are similar to published studies based on body-mass extrapolations
      from studies in adults. As such, applying current (99m)Tc-sestamibi dosing
      regimens for 1- and 2-d protocols based on those extrapolations will result in
      the expected radiation dose in children and adolescents.

PMID- 25858046
TI  - Scintillating balloon-enabled fiber-optic system for radionuclide imaging of
      atherosclerotic plaques.
AB  - Atherosclerosis underlies coronary artery disease, the leading cause of death in
      the United States and worldwide. Detection of coronary plaque inflammation
      remains challenging. In this study, we developed a scintillating balloon-enabled
      fiber-optic radionuclide imaging (SBRI) system to improve the sensitivity and
      resolution of plaque imaging using (18)F-FDG, a marker of vascular inflammation,
      and tested it in a murine model. METHODS: The fiber-optic system uses a
      Complementary Metal-Oxide Silicon (CMOS) camera with a distal ferrule terminated
      with a wide-angle lens. The novelty of this system is a scintillating balloon in
      the front of the wide-angle lens to image light from the decay of (18)F-FDG
      emission signal. To identify the optimal scintillating materials with respect to
      resolution, we calculated the modulation transfer function of yttrium-aluminum
      garnet doped with cerium, anthracene, and calcium fluoride doped with europium
      (CaF2:Eu) phosphors using an edge pattern and a thin-line optical phantom. The
      scintillating balloon was then fabricated from 10 mL of silicone RTV catalyst
      mixed with 1 mL of base and 50 mg of CaF2:Eu per mL. The addition of a lutetium
      oxyorthosilicate scintillating crystal (500 MUm thick) to the balloon was also
      investigated. The SBRI system was tested in a murine atherosclerosis model:
      carotid-ligated mice (n = 5) were injected with (18)F-FDG, followed by ex vivo
      imaging of the macrophage-rich carotid plaques and nonligated controls.
      Confirmatory imaging of carotid plaques and controls was also performed by an
      external optical imaging system and autoradiography. RESULTS: Analyses of the
      different phosphors showed that CaF2:Eu enabled the best resolution of 1.2 MUm.
      The SBRI system detected almost a 4-fold-higher radioluminescence signal from the
      ligated left carotid artery than the nonligated right carotid: 1.63 * 10(2) +/-
      4.01 * 10(1) vs. 4.21 * 10(1) +/- 2.09 * 10(0) (photon counts), P = 0.006. We
      found no significant benefit to adding a scintillating crystal to the balloon:
      1.65 * 10(2) +/- 4.07 * 10(1) vs. 4.44 * 10(1) +/- 2.17 * 10(0) (photon counts),
      P = 0.005. Both external optical imaging and autoradiography confirmed the high
      signal from the (18)F-FDG in carotid plaques versus controls. CONCLUSION: This
      SBRI system provides high-resolution and sensitive detection of (18)F-FDG uptake
      by murine atherosclerotic plaques.

PMID- 25858048
TI  - Resuscitating PROPPRly.

PMID- 25858049
TI  - A highly planar fluorinated benzothiadiazole-based conjugated polymer for high
      performance organic thin-film transistors.
AB  - High-mobility and low-voltage-operated organic field-effect transistors (OFETs)
      are demonstrated by the design of a new fluorinated benzothiadiazole-based
      conjugated polymer with fluorinated high-k polymer dielectrics. A record-breaking
      high hole mobility of 9.0 cm(2) V(-1) s(-1) for benzothiadiazole-based
      semiconducting polymers is achieved by the excellent planarity of the
      semiconducting polymer. 

PMID- 25858047
TI  - Local and serum levels of adipokines in patients with obesity after periodontal
      therapy: one-year follow-up.
AB  - AIM: This study evaluated the effects of scaling and root planing (SRP) on
      gingival crevicular fluid (GCF) and serum levels of adipokines in patients with
      chronic periodontitis (CP) with or without obesity. METHODS: Twenty patients with
      obesity and 20 patients without obesity, all with CP, received SRP. Serum and GCF
      levels of resistin, adiponectin, leptin, tumour necrosis factor [TNF]-alpha and
      interleukin [IL]-6 were evaluated by enzyme-linked immunosorbent assay at
      baseline, 3, 6 and 12 months post-therapy. RESULTS: SRP reduced the amounts of
      TNF-alpha in deep sites and increased the concentration of adiponectin in shallow
      sites of non-obese patients (p < 0.05). SRP increased the concentrations of TNF
      alpha and leptin in patients with obesity (p < 0.05). GCF levels of TNF-alpha
      were higher in patients with obesity than in patients without obesity at all time
      points (p < 0.05). There were no changes in serum levels of any adipokines for
      any group after therapy (p > 0.05). Patients with obesity exhibited higher serum
      levels of leptin at all time-points and IL-6 at 3 months post-therapy (p < 0.05).
      CONCLUSIONS: Obesity may modulate systemic and periodontal levels of adipokines
      in favour of pro-inflammation, independently of periodontal therapy. SRP did not
      affect the circulating levels of adipokines in patients with or without obesity.

PMID- 25858051
TI  - 17(th) Congress of the European Society for Sexual Medicine.

PMID- 25858052
TI  - Proceedings of the 17(th) Annual Congress of the European Society for Sexual
      Medicine, Copenhagen, Denmark, February 5-7, 2015.

PMID- 25858050
TI  - Long-term outcome of patients with severe biventricular heart failure and severe
      mitral regurgitation after percutaneous edge-to-edge mitral valve repair.
AB  - OBJECTIVE: To assess long-term outcome and parameters associated with poor and
      favorable outcome in patients with a left ventricular ejection fraction (LV-EF)
      <=25% and severe mitral regurgitation (MR) after percutaneous edge-to-edge mitral
      valve repair (pMVR). BACKGROUND: There is no data on long-term outcome in this
      cohort of patients. METHODS: We analyzed all 34 patients with a LV-EF <=25% and
      severe MR treated with pMVR in 2 university hospitals from 2009 to 2012. RESULTS:
      Mitral regurgitation could be successfully reduced to grade <=2 in 30 patients
      (88%). Long-term follow-up (up to 5 years) revealed a steep decline of the
      survival curve reaching 50% already 8 month after pMVR. In contrast, estimated
      survival of the remaining patients showed a favorable long-term outcome. Patients
      deceased during the first year presented with higher right ventricular tricuspid
      pressure gradient (RVTG) (44.5 +/- 8.4 mmHg vs. 35.2 +/- 15.4 mmHg, P = 0.035)
      and worse RV-function (P = 0.014) prior to the procedure. One-year mortality of
      patients with pulmonary hypertension and depressed RV-function (n = 22) was very
      high (77%) compared to the remaining patients (n = 12, mortality rate of 0%, P =
      0.0001). CONCLUSIONS: Although pMVR lead to a successful reduction of MR in
      patients with a LV-EF <=25%, 1-year mortality in this cohort was very high.
      However, a subgroup of patients showed a favorable long-term outcome after pMVR.
      Especially the right ventricular parameters sustained RV-function and absence of
      pulmonary hypertension-easily assessed with echocardiography-might be used to
      identify this subgroup and encourage pMVR in these patients.

PMID- 25858053
TI  - Safety of subcutaneous immunotherapy with inhalant allergen extracts: a single
      center 30-year experience from Turkey.
AB  - CONTEXT: Although subcutaneous allergen immunotherapy (SCIT) is effective in
      allergic rhinitis (AR) and asthma, it carries a risk of local and systemic
      adverse reactions. OBJECTIVE: The aim of this study was to evaluate the rates and
      clinical characteristics of local and systemic reactions (LR and SR), and to
      identify their relation of demographic features, allergen extracts and diagnosis.
      MATERIALS AND METHODS: This study analyzed the administration of SCIT from 1983
      to 2013; involving 1816 patients affected by allergic asthma and/or AR. RESULTS:
      The rates of SR from SCIT were 0.078% per injection and 9% per patient. According
      to the World Allergy Organization 2010 grading system, 91 grade 1 reactions
      (44%), 67 grade 2 reactions (32.3%), 33 grade 3 reactions (16%) and 16 grade 4
      reactions (7.7%) were seen. There was no fatal outcome from any of the SRs. Risk
      factors for a SR included: aluminium-adsorbed extract, pollen-containing
      vaccines, large LR and recurrent (>=2) LRs. The total LR rates were 0.062% per
      injection and 5.2% per patient; the small LR rates were 0.027% per injection and
      2.3% per patient, and the large LR rate were 0.035% per injection and 2.9% per
      patient. Female gender, depot extracts, calcium phosphate-adsorbed extract and
      pollen vaccines were identified as risk factors for LR. CONCLUSION: The analysis
      of our data over a 30-year period confirmed that SCIT with inhalant allergens
      conducted strictly according to the standard protocols and when administrated by
      experienced staff is a safe method of treatment with only a few side-effects.

PMID- 25858054
TI  - Survey-Defined Patient Experiences With Aspirin-Exacerbated Respiratory Disease.
AB  - BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is a chronic illness
      of progressive recurrent sinus disease with nasal polyps and asthma. No
      population-based comprehensive surveys of patients with AERD have been carried
      out to assess specific quality-of-life impact or perceptions of treatment
      benefit. OBJECTIVE: This survey analyzed perceptions and quality of life in those
      living with AERD and queried patient observations of treatment effectiveness. The
      survey assessed whether dietary and nutritional support was used to manage AERD,
      and if so, whether there was a perceived benefit. METHODS: This survey was
      publicized through clinics that treat patients with AERD, Web sites, and online
      blogs. RESULTS: Results are reported for 190 patients. Most subjects reported an
      adverse effect of AERD on quality of life. Chronic nasal symptoms followed by
      decreased sense of smell were reported to have the greatest impact on quality of
      life-in 81 (43%) and 74 (39%), respectively. Those who lost their ability to
      smell (n = 65; 34%) reported that they missed the enjoyment of food and eating
      the most. A minority indicated that a combination of medications (aspirin,
      leukotriene receptor antagonist, zileuton, or omalizumab) was more effective than
      1 alone. Of those surveyed, 120 (63%) respondents felt that components of their
      diet contributed to their disease and 147 (77%) respondents reported having
      reactions after alcohol consumption. CONCLUSIONS: Patients with AERD live with
      frustration and report a poor quality of life in spite of several pharmacologic
      treatments including aspirin desensitization followed by daily aspirin. Despite
      ongoing medical therapy, the burden of disease in AERD remains high.

PMID- 25858055
TI  - Anaphylaxis after hymenoptera sting: is it venom allergy, a clonal disorder, or
      both?
AB  - A 47-year-old man presented with loss of consciousness 5 minutes after being
      stung by a yellow jacket in his backyard. Epinephrine and fluids were required
      for resuscitation. Allergy evaluation revealed specific IgE to yellow jacket and
      honeybee, and the patient was started on venom immunotherapy. He had systemic
      reactions during buildup and a severe anaphylactic episode requiring 3 doses of
      intramuscular epinephrine at maintenance doses. Immunotherapy was discontinued.
      Serum tryptase level after 1 such episode was 29 ng/mL, with a baseline level of
      25 ng/mL 4 weeks later. The physical examination was unremarkable including no
      skin lesions of cutaneous mastocytosis. Because of elevated baseline tryptase
      level, a bone marrow biopsy was performed, which revealed multifocal dense
      infiltrates of mast cells. A diagnosis of systemic mastocytosis was made. The
      patient was treated with omalizumab and was able to tolerate immunotherapy and is
      currently maintained on lifelong immunotherapy. He was restung in the field and
      has not had anaphylaxis. 

PMID- 25858056
TI  - Cardiac actions of atrial natriuretic peptide: new visions of an old friend.

PMID- 25858058
TI  - The direct actions of flecainide on the human cardiac ryanodine receptor: keeping
      open the debate on the mechanism of action of local anesthetics in CPVT.

PMID- 25858057
TI  - Exosomes: nanosized cellular messages.

PMID- 25858060
TI  - Cardiac cell therapy: lost in meta-analyses.

PMID- 25858059
TI  - Cell therapy for patients with acute myocardial infarction: ACCRUEd evidence to
      date.

PMID- 25858061
TI  - Leptin beyond the lipostat: key component of blood pressure regulation.

PMID- 25858062
TI  - Matching taxpayer funding to population health needs.
AB  - In an era of economic recession and budget cutbacks,Americans may be curious to
      know how the government is distributing their taxes for medical research,
      relative to their health needs. Previous reports recommended that the National
      Institutes of Health (NIH) allocate funding proportional to the burden-of-illness
      from diseases and conditions. But the most recent publicly available data on
      burden-of-illness and NIH funding show that infectious diseases are still
      overfunded relative to their health burden on the American population, especially
      HIV/AIDS. By contrast, several lifestyle/environmental health conditions are
      still underfunded, including importantly: chronic obstructive pulmonary disease,
      lung cancer, stroke, heart disease, depression, violence, and road injury. NIH's
      allocation of research funding is often disproportionate to the current health
      needs of the American people. Greater decision-making involvement of Congress and
      the public would be helpful, if Americans want their taxes spent fairly on the
      illnesses that actually burden their health.

PMID- 25858063
TI  - Matching taxpayer funding to population health needs: not so simple.

PMID- 25858064
TI  - Direct cardiac reprogramming: progress and challenges in basic biology and
      clinical applications.
AB  - The discovery of induced pluripotent stem cells changed the field of regenerative
      medicine and inspired the technological development of direct reprogramming or
      the process by which one cell type is directly converted into another without
      reverting a stem cell state by overexpressing lineage-specific factors. Indeed,
      direct reprogramming has proven sufficient in yielding a diverse range of cell
      types from fibroblasts, including neurons, cardiomyocytes, endothelial cells,
      hematopoietic stem/progenitor cells, and hepatocytes. These studies revealed that
      somatic cells are more plastic than anticipated, and that transcription factors,
      microRNAs, epigenetic factors, secreted molecules, as well as the cellular
      microenvironment are all important for cell fate specification. With respect to
      the field of cardiology, the cardiac reprogramming presents as a novel method to
      regenerate damaged myocardium by directly converting endogenous cardiac
      fibroblasts into induced cardiomyocyte-like cells in situ. The first in vivo
      cardiac reprogramming reports were promising to repair infarcted hearts; however,
      the low induction efficiency of fully reprogrammed, functional induced
      cardiomyocyte-like cells has become a major challenge and hampered our
      understanding of the reprogramming process. Nevertheless, recent studies have
      identified several critical factors that may affect the efficiency and quality of
      cardiac induction and have provided new insights into the mechanisms of cardiac
      reprogramming. Here, we review the progress in direct reprogramming research and
      discuss the perspectives and challenges of this nascent technology in basic
      biology and clinical applications. 

PMID- 25858065
TI  - Vascular wall progenitor cells in health and disease.
AB  - The vasculature plays an indispensible role in organ development and maintenance
      of tissue homeostasis, such that disturbances to it impact greatly on
      developmental and postnatal health. Although cell turnover in healthy blood
      vessels is low, it increases considerably under pathological conditions. The
      principle sources for this phenomenon have long been considered to be the
      recruitment of cells from the peripheral circulation and the re-entry of mature
      cells in the vessel wall back into cell cycle. However, recent discoveries have
      also uncovered the presence of a range of multipotent and lineage-restricted
      progenitor cells in the mural layers of postnatal blood vessels, possessing high
      proliferative capacity and potential to generate endothelial, smooth muscle,
      hematopoietic or mesenchymal cell progeny. In particular, the tunica adventitia
      has emerged as a progenitor-rich compartment with niche-like characteristics that
      support and regulate vascular wall progenitor cells. Preliminary data indicate
      the involvement of some of these vascular wall progenitor cells in vascular
      disease states, adding weight to the notion that the adventitia is integral to
      vascular wall pathogenesis, and raising potential implications for clinical
      therapies. This review discusses the current body of evidence for the existence
      of vascular wall progenitor cell subpopulations from development to adulthood and
      addresses the gains made and significant challenges that lie ahead in trying to
      accurately delineate their identities, origins, regulatory pathways, and
      relevance to normal vascular structure and function, as well as disease. 

PMID- 25858066
TI  - Use of mesenchymal stem cells for therapy of cardiac disease.
AB  - Despite substantial clinical advances over the past 65 years, cardiovascular
      disease remains the leading cause of death in America. The past 15 years has
      witnessed major basic and translational interest in the use of stem and precursor
      cells as a therapeutic agent for chronically injured organs. Among the cell types
      under investigation, adult mesenchymal stem cells are widely studied, and in
      early stage, clinical studies show promise for repair and regeneration of cardiac
      tissues. The ability of mesenchymal stem cells to differentiate into mesoderm-
      and nonmesoderm-derived tissues, their immunomodulatory effects, their
      availability, and their key role in maintaining and replenishing endogenous stem
      cell niches have rendered them one of the most heavily investigated and
      clinically tested type of stem cell. Accumulating data from preclinical and early
      phase clinical trials document their safety when delivered as either autologous
      or allogeneic forms in a range of cardiovascular diseases, but also importantly
      define parameters of clinical efficacy that justify further investigation in
      larger clinical trials. Here, we review the biology of mesenchymal stem cells,
      their interaction with endogenous molecular and cellular pathways, and their
      modulation of immune responses. Additionally, we discuss factors that enhance
      their proliferative and regenerative ability and factors that may hinder their
      effectiveness in the clinical setting. 

PMID- 25858067
TI  - The hippo pathway in heart development, regeneration, and diseases.
AB  - The heart is the first organ formed during mammalian development. A properly
      sized and functional heart is vital throughout the entire lifespan. Loss of
      cardiomyocytes because of injury or diseases leads to heart failure, which is a
      major cause of human morbidity and mortality. Unfortunately, regenerative
      potential of the adult heart is limited. The Hippo pathway is a recently
      identified signaling cascade that plays an evolutionarily conserved role in organ
      size control by inhibiting cell proliferation, promoting apoptosis, regulating
      fates of stem/progenitor cells, and in some circumstances, limiting cell size.
      Interestingly, research indicates a key role of this pathway in regulation of
      cardiomyocyte proliferation and heart size. Inactivation of the Hippo pathway or
      activation of its downstream effector, the Yes-associated protein transcription
      coactivator, improves cardiac regeneration. Several known upstream signals of the
      Hippo pathway such as mechanical stress, G-protein-coupled receptor signaling,
      and oxidative stress are known to play critical roles in cardiac physiology. In
      addition, Yes-associated protein has been shown to regulate cardiomyocyte fate
      through multiple transcriptional mechanisms. In this review, we summarize and
      discuss current findings on the roles and mechanisms of the Hippo pathway in
      heart development, injury, and regeneration. 

PMID- 25858068
TI  - Role of mechanotransduction in vascular biology: focus on thoracic aortic
      aneurysms and dissections.
AB  - Thoracic aortic diseases that involve progressive enlargement, acute dissection,
      or rupture are influenced by the hemodynamic loads and mechanical properties of
      the wall. We have only limited understanding, however, of the mechanobiological
      processes that lead to these potentially lethal conditions. Homeostasis requires
      that intramural cells sense their local chemomechanical environment and
      establish, maintain, remodel, or repair the extracellular matrix to provide
      suitable compliance and yet sufficient strength. Proper sensing, in turn,
      necessitates both receptors that connect the extracellular matrix to
      intracellular actomyosin filaments and signaling molecules that transmit the
      related information to the nucleus. Thoracic aortic aneurysms and dissections are
      associated with poorly controlled hypertension and mutations in genes for
      extracellular matrix constituents, membrane receptors, contractile proteins, and
      associated signaling molecules. This grouping of factors suggests that these
      thoracic diseases result, in part, from dysfunctional mechanosensing and
      mechanoregulation of the extracellular matrix by the intramural cells, which
      leads to a compromised structural integrity of the wall. Thus, improved
      understanding of the mechanobiology of aortic cells could lead to new therapeutic
      strategies for thoracic aortic aneurysms and dissections. 

PMID- 25858069
TI  - Mechanotransduction in cardiac hypertrophy and failure.
AB  - Cardiac muscle cells have an intrinsic ability to sense and respond to mechanical
      load through a process known as mechanotransduction. In the heart, this process
      involves the conversion of mechanical stimuli into biochemical events that induce
      changes in myocardial structure and function. Mechanotransduction and its
      downstream effects function initially as adaptive responses that serve as
      compensatory mechanisms during adaptation to the initial load. However, under
      prolonged and abnormal loading conditions, the remodeling processes can become
      maladaptive, leading to altered physiological function and the development of
      pathological cardiac hypertrophy and heart failure. Although the mechanisms
      underlying mechanotransduction are far from being fully elucidated, human and
      mouse genetic studies have highlighted various cytoskeletal and sarcolemmal
      structures in cardiac myocytes as the likely candidates for load transducers,
      based on their link to signaling molecules and architectural components important
      in disease pathogenesis. In this review, we summarize recent developments that
      have uncovered specific protein complexes linked to mechanotransduction and
      mechanotransmission within the sarcomere, the intercalated disc, and at the
      sarcolemma. The protein structures acting as mechanotransducers are the first
      step in the process that drives physiological and pathological cardiac
      hypertrophy and remodeling, as well as the transition to heart failure, and may
      provide better insights into mechanisms driving mechanotransduction-based
      diseases. 

PMID- 25858072
TI  - Highlight on mouse endocan.

PMID- 25858073
TI  - Activation of the Albino Sterlet Acipenser ruthenus Eggs by UV-Irradiated Bester
      Hybrid Spermatozoa to Provide Gynogenetic Progeny.
AB  - Meiotic gynogenesis was induced in the albino form of sterlet Acipenser ruthenus
      by activation of eggs with UV-irradiated bester (Huso huso x Acipenser ruthenus)
      spermatozoa followed by inhibition of the second meiotic division performed by a
      heat shock. Obtained putative gynogenetic progeny were all albinos. The genetic
      verification based on three microsatellite DNA markers confirmed the only
      maternal inheritance of the progeny from the gynogenetic experimental groups.
      Cytogenetic analysis proved the gynogenetic sterlets were diploids. Application
      of the albino phenotype together with the molecular and the cytogenetic
      diagnostic approaches enabled to evaluate the efficiency of the spermatozoa
      irradiation and application of the heat shock to restore diploid state in the
      gynogenetic zygotes. 

PMID- 25858074
TI  - The effect of dispersion forces on the interaction energies and far infrared
      spectra of protic ionic liquids.
AB  - We could show by means of dispersion-corrected DFT calculations that the
      interaction energy in protic ionic liquids can be dissected into Coulomb
      interaction, hydrogen bonding and dispersion interaction. The H-bond energy as
      well as the dispersion energy can be quantified to be 50 kJ mol(-1) each
      representing ten percent of the overall interaction energy. The dispersion
      interaction could be dissected into two portions. One third could be related to
      the dispersion interaction within an ion-pair enhancing the H-bond strength, two
      thirds stem from dispersion interaction between the ion-pairs. This distribution
      of dispersion interaction is reflected in the far infrared (FIR) spectra. The H
      bond band is shifted weaker than the low frequency band where the latter
      indicates diffuse cation-anion interaction and H-bond bending motions. Finally,
      we can dissect the different types of interaction energies indicating their
      characteristic influence on vibrational modes in the FIR. 

PMID- 25858070
TI  - Molecular mechanisms of mitochondrial autophagy/mitophagy in the heart.
AB  - Mitochondrial quality is a crucial determinant of cell viability, and
      mitochondrial autophagy plays a central role in this control mechanism. Based on
      studies in yeast, numerous investigations of this process have been conducted,
      and the framework of mammalian mitochondrial autophagy is progressively
      appearing. However, many enigmas about the molecular mechanisms involved remain
      unsolved. Furthermore, the pathological significance of mitochondrial autophagy
      in the heart remains largely unclear. In this review, we discuss the current
      understanding of mitochondrial autophagy in mammals with reference to that in
      yeast. Regarding the process in yeast, some points of uncertainty have arisen. We
      also summarize recent advances in the research of autophagy and mitochondrial
      autophagy in the heart. This article is a part of a review series on Autophagy in
      Health and Disease. 

PMID- 25858071
TI  - DPP4 in cardiometabolic disease: recent insights from the laboratory and clinical
      trials of DPP4 inhibition.
AB  - The discovery of incretin-based medications represents a major therapeutic
      advance in the pharmacological management of type 2 diabetes mellitus (T2DM), as
      these agents avoid hypoglycemia, weight gain, and simplify the management of
      T2DM. Dipeptidyl peptidase-4 (CD26, DPP4) inhibitors are the most widely used
      incretin-based therapy for the treatment of T2DM globally. DPP4 inhibitors are
      modestly effective in reducing HbA1c (glycated hemoglobin) (~0.5%) and while
      these agents were synthesized with the understanding of the role that DPP4 plays
      in prolonging the half-life of incretins such as glucagon-like peptide-1 and
      gastric inhibitory peptide, it is now recognized that incretins are only one of
      many targets of DPP4. The widespread expression of DPP4 on blood vessels,
      myocardium, and myeloid cells and the nonenzymatic function of CD26 as a
      signaling and binding protein, across a wide range of species, suggest a
      teleological role in cardiovascular regulation and inflammation. Indeed, DPP4 is
      upregulated in proinflammatory states including obesity, T2DM, and
      atherosclerosis. Consistent with this maladaptive role, the effects of DPP4
      inhibition seem to exert a protective role in cardiovascular disease at least in
      preclinical animal models. Although 2 large clinical trials suggest a neutral
      effect on cardiovascular end points, current limitations of performing trials in
      T2DM over a limited time horizon on top of maximal medical therapy must be
      acknowledged before rendering judgment on the cardiovascular efficacy of these
      agents. This review will critically review the science of DPP4 and the effects of
      DPP4 inhibitors on the cardiovascular system. 

PMID- 25858076
TI  - A Possible Freshness Marker for Royal Jelly: Formation of 5-Hydroxymethyl-2
      furaldehyde as a Function of Storage Temperature and Time.
AB  - In this article we present a study of the variability of the concentration of 5
      hydroxymethyl-2-furaldehyde (HMF) in natural royal jelly (RJ) as a function of
      its storage temperature (-18, 4, and 25  degrees C) and time (up to 9 months
      after harvesting). For this work HMF is evaluated using an RP-HPLC method we
      previously assessed. While all RJ samples stored at 4 and -18  degrees C always
      showed levels of HMF under the limit of detection (0.13 mg kg(-1)), samples kept
      at 25  degrees C showed an exponential increase in the concentration of HMF as a
      function of the storage time. This behavior and a number of desirable features of
      the analytical method used (ease of use in routine laboratories, availability of
      a complete validation protocol specifically developed for RJ, based on
      consolidated chemical knowledge) allow us to hypothesize the use of HMF as a
      possible, reliable freshness marker for RJ. 

PMID- 25858075
TI  - APF lncRNA regulates autophagy and myocardial infarction by targeting miR-188-3p.
AB  - The abnormal autophagy is associated with a variety of cardiovascular diseases.
      Long noncoding RNAs (lncRNAs) are emerging as new factors in gene regulation, but
      how lncRNAs operate in the regulation of autophagy in the heart is unclear. Here
      we report that a long noncoding RNA, named autophagy promoting factor (APF), can
      regulate autophagic cell death by targeting miR-188-3p and ATG7. The results show
      that miR-188-3p suppresses autophagy and myocardial infarction by targeting ATG7.
      Further, we find that APF lncRNA regulates miR-188-3p, and thus affects ATG7
      expression, autophagic cell death and myocardial infarction. Our present study
      reveals a novel regulating model of autophagic programme, which comprises APF,
      miR-188-3p and ATG7 in the heart. Modulation of their levels may serve as
      potential targets and diagnostic tools for novel therapeutic strategies of
      myocardial infarction and heart failure. 

PMID- 25858077
TI  - Deep cuts to India's health spending will delay universal access to healthcare.

PMID- 25858078
TI  - Clinical and sociodemographic predictors of oral pain and eating problems among
      adult and senior Spaniards in the national survey performed in 2010.
AB  - BACKGROUND: Pain and chewing difficulties have been identified as the strongest
      predictors of oral disadvantage. The aim of this study is to analyze and quantify
      the sociodemographic, behavioural and clinical factors modulating the oral pain
      and eating difficulties reported by Spanish adults and elderly Spanish people in
      the last National Oral Health Survey performed in 2010. STUDY DESIGN: Data
      concerning pain and chewing difficulties were acquired on a Likert-scale format
      from a representative sample of the Spanish general population with ages between
      35-44 years (n=391) and 65-74 years (n=405). Risk factors were identified using
      bivariate analysis, after which the crude association between risk factors
      (sociodemographic, behavioural and clinical) and outcome variables (pain and
      eating problems) was assessed by adjusted odds ratios, calculated by means of
      multivariate logistic regression. RESULTS: Eating problems and oral pain were
      mainly associated with prosthetic and caries treatment needs as clinical
      predictors, but female sex was also seen to be a relevant and significant risk
      factor for suffering pain and eating restrictions. Paradoxically, after taking
      into account all the aforementioned predictors, the adults had an almost two-fold
      higher risk of reporting pain or eating difficulties than the elderly subjects.
      CONCLUSIONS: In agreement with the results from the last national oral health
      survey, prosthetic and caries treatment needs should be considered key factors in
      determining the oral well-being of the Spanish population. In sociodemographic
      terms, the women and adults were seen to be at a significantly higher risk of
      suffering pain and eating restrictions.

PMID- 25858079
TI  - Evaluation of pretreatment serum interleukin-6 and tumour necrosis factor alpha
      as a potential biomarker for recurrence in patients with oral squamous cell
      carcinoma.
AB  - BACKGROUND: Oral squamous cell carcinoma (OSCC) constitutes 3 percent of all
      cancers with predominant occurrence in middle aged and elderly males. Tumour
      recurrence worsens disease prognosis and decreases quality of life in patients
      with OSCC. Proinflammatory cytokines such as interleukin-6 (IL-6) and tumour
      necrosis factor alpha (TNF-alpha) have been suggested to play a certain role in
      variety of tumours. The aim of this study was to investigate the relationship of
      pretreatment serum IL-6 and TNF-alpha levels on tumour recurrence in patients
      with OSCC in order to identify potential biomarkers for the early detection of
      disease recurrence. MATERIAL AND METHODS: The patients with newly diagnosed OSCC
      were treated and followed from the first visit from November 2006 until January
      2008. Serum IL-6 and TNF-alpha concentrations were measured. The records of the
      patients were re-examined in July 2012 and data were recorded about cancer
      characteristics and tumour recurrence. Disease free survival was analyzed by
      Kaplan-Meier survival curves, log rank test and Cox proportional hazards
      regression. RESULTS: Serum IL-6 was shown as an independent risk factor for
      tumour recurrence. CONCLUSIONS: Pretreatment serum IL-6 concentration may be a
      useful biomarker for identification of OSCC patients with increased risk of the
      disease recurrence.

PMID- 25858080
TI  - Metallothionein immunoexpression in non-syndromic and syndromic keratocystic
      odontogenic tumour.
AB  - BACKGROUND: To compare the metallothionein (MT) immunoexpression in non-syndromic
      and syndromic keratocystic odontogenic tumour (KOT), to correlate MT with
      cellular proliferation, and to evaluate the influence of inflammation in MT.
      STUDY DESIGN: Fourteen cases of KOT were submitted to immunohistochemistry for MT
      and Ki-67 analysis. The lesions were grouped according to their grade of
      inflammation, and statistical analysis was performed. RESULTS: MT was higher in
      non-syndromic KOT than in syndromic KOT (p<0.05). No statistical difference in Ki
      67 could be identified; however, an inverse correlation was observed between MT
      and Ki-67 in both lesions. When analysing inflammation, non-syndromic KOT showed
      no differences in either MT or Ki-67. CONCLUSIONS: The MT immunophenotype of
      syndromic KOT was different from non-syndromic KOT. MT might not be involved in
      the proliferation control of both KOT. MT and Ki-67 immunoexpressions proved to
      be unaffected by inflammation in non-syndromic KOT.

PMID- 25858081
TI  - Coronectomy versus surgical removal of the lower third molars with a high risk of
      injury to the inferior alveolar nerve. A bibliographical review.
AB  - BACKGROUND: Coronectomy is the surgical removal of the crown of the tooth
      deliberately leaving part of its roots. This is done with the hope of eliminating
      the pathology caused, and since the roots are still intact, the integrity of the
      inferior alveolar nerve is preserved. OBJECTIVE: The aim is to carry out a
      systematic review in order to be able to provide results and conclusions with the
      greatest scientific evidence possible. MATERIAL AND METHODS: A literature review
      is carried out through the following search engines: Pubmed MEDLINE, Scielo,
      Cochrane library and EMI. The level of evidence criteria from the Agency for
      Healthcare Research and Quality was applied, and the clinical trials' level of
      quality was analyzed by means of the JADAD criteria. RESULTS: The following
      articles were obtained which represents a total of 17: 1 systematic review, 2
      randomized clinical trials and 2 non-randomized clinical trials, 3 cohort
      studies, 2 retrospective studies, 3 case studies and 4 literature reviews.
      CONCLUSIONS: Coronectomy is an adequate preventative technique in protecting the
      inferior alveolar nerve, which is an alternative to the conventional extraction
      of third molars, which unlike the former technique, presents a high risk of
      injury to the inferior alveolar nerve. However, there is a need for new clinical
      studies, with a greater number of samples and with a longer follow-up period in
      order to detect potential adverse effects of the retained roots.

PMID- 25858082
TI  - Awareness of complications and maintenance mode of oral piercing in a group of
      adolescents and young Italian adults with intraoral piercing.
AB  - BACKGROUND: The aim of the study was to focus the awareness of complications of
      oral piercing among a group of adolescents and young Italian adults with
      intraoral piercings. MATERIAL AND METHODS: A total of 225 teenagers were asked to
      complete a questionnaire on the awareness of complications of oral piercing. An
      additional questionnaire was administered in case of oral piercing worn, based on
      site piercing, knowledge about piercer license, oral and systemic risks due to
      oral piercing, disinfection and sterilization of the material pierced,
      information by the piercer about piercing hygiene maintenance and post-piercing
      dentist check-up. After questionnaire all participants received a brochure with
      some information about risks and maintenance mode of piercing. RESULTS: Data
      revealed that more than 50% of teens surveyed was found to wear a piercing. Only
      25.3% was aware of the risk of HCV cross-infection and only 17.3% reported of
      knowledge about risk of endocarditis. Only 17% checked the piercer license and
      only 18% sterilization and disinfection of the materials used. 53.7% did not
      received explanations about the risks associated with piercing. With regard to
      the maintenance mode of the piercing, it has been suggested to brush the piercing
      bar in 17% of cases. The post piercing specialist visits have been suggested only
      in 7% of cases. CONCLUSIONS: The general lack of awareness of complications and
      maintenance mode related to oral piercing needs to be addressed by some education
      programs performed at school and by dentists.

PMID- 25858083
TI  - Complications in the treatment with alveolar extraosseous distractors. Literature
      review.
AB  - BACKGROUND: To review the literature that analyses the types and frequency of
      complications associated with the use of extraosseous alveolar distraction from
      2007 to 2013. MATERIAL AND METHOD: Review of the literature in PubMed, using
      these keywords; alveolar ridge, alveolar distraction osteogenesis, complication,
      literature review. Inclusion criteria were: articles published between 2007 and
      2013 that included the distraction protocol, the complications encountered and
      the time when they occurred. RESULTS: According to the above criteria, 12
      articles were included in this review, where 334 extraosseous distractors were
      placed and 395 complications were encountered, of which 19 (4.81%) were
      intraoperative, 261 (66.07%) postoperative and 115 (29.11 %) were post
      distraction. The most common complication was the incorrect distraction vector
      found in 105 cases (26.58%), in 23 cases (5.82%) there were severe complications,
      of which 14 (3.54%) were mandibular fracture and 9 (2.27%) were fractures of the
      distractor elements. CONCLUSIONS: According to this review, although alveolar
      distraction is a safe and predictable technique, it can cause complications;
      however, they are usually minor and easily resolved without affecting the
      treatment outcome.

PMID- 25858084
TI  - CT maxillary sinus evaluation--A retrospective cohort study.
AB  - BACKGROUND: Proximity of the dental roots to the sinus floor makes dental disease
      a probable cause of maxillary sinusitis. The aim of this study was to find out if
      maxillary sinus pathologic changes were more prevalent in patients with dental
      disease and to evaluate the performance of computed tomography (CT) in analyzing
      and detecting apical periodontitis and other odontogenic causes on the maxillary
      sinusitis etiology in a Portuguese Caucasian population. MATERIAL AND METHODS:
      Retrospective cohort study. The total sample of 504 patients and their CT was
      included in this study. The patients were from a private dental clinic,
      specializing in oral surgery, where the first complaint was not directly related
      to sinus disease, but with dental pathology. For each patient, the etiological
      factors of maxillary sinusitis and the imaging CT findings were analyzed. All the
      axial, coronal and sagittal CT slices were evaluated and general data were
      registered. The latter was selected based on the maxillary sinus CT published
      literature. RESULTS: 32.40% of patients presented normal sinus (without any
      etiological factor associated), 29.00% showed presence of etiological and imaging
      findings in the maxillary sinus, 20.60% had only imaging changes in the maxillary
      sinus and 18.00% of patients presented only etiological factors and no change in
      the maxillary sinus. CONCLUSIONS: Radiological imaging is an important tool for
      establishing the diagnosis of maxillary sinus pathology. These results indicate
      that the CT scan should be an excellent tool for complement the odontogenic
      sinusitis diagnosis.

PMID- 25858085
TI  - Comparison of success rate and onset time of two different anesthesia techniques.
AB  - BACKGROUND: Using local anesthetic is common to control the pain through blocking
      the nerve reversibly in dental procedures. Gow-Gates (GG) technique has a high
      success rate but less common. This study aimed to compare the onset time and
      success rate in GG and standard technique of inferior alveolar nerve block
      (IANB). STUDY DESIGN: This descriptive, single blind study was consisted of 136
      patients (59 males and 77 females) who were randomly received GG or IANB for
      extraction of mandibular molar teeth. Comparisons between the successes of two
      anesthetic injection techniques were analyzed with Chi-square test. Incidence of
      pulpal anesthesia and soft tissue anesthesia were analyzed with Kaplan-Meier
      method. Mean onset times of pulpal anesthesia, soft tissue and lip numbness were
      analyzed with Log-Rank test. Comparisons were considered significant at P<=0.05
      by using SPSS software ver.15. RESULTS: The incidence of pulpal anesthesia in the
      IANB group (canine 49.3%, premolar 60.3%) were not significantly different from
      the GG group (canine 41.3%, premolar 74.6%) (P=0.200 and P=0.723). The success
      rate in the IANB group (80.82%) was not significantly different from the GG group
      (92.02%) (P=0.123). Furthermore, onset time of lip and buccal soft tissue
      numbness in GG group (3.25, 4.96 minutes) was quite similar to IANB group (3.22,
      4.89 minutes) (all P values >0.05). CONCLUSIONS: Although this study demonstrated
      higher clinical success rate for GG than IANB technique, no significant
      differences in success rates and onset time were observed between two techniques.

PMID- 25858086
TI  - Analysis of 126 hospitalized elder maxillofacial trauma victims in central China.
AB  - BACKGROUND: The aim of this study was to analyzed the characteristics and
      treatment of maxillofacial injuries in the elder patients with maxillofacial
      injuries in central China. MATERIAL AND METHODS: We retrospectively analyzed the
      characteristics and treatment of maxillofacial injuries in the patients over the
      age of 60 to analyze the trends and clinical characteristics of maxillofacial
      trauma in elder patients from the First Affiliated Hospital of Zhengzhou
      University (from 2010 to 2013) in central China and to present recommendations on
      prevention and management. RESULTS: Of the 932 patients with maxillofacial
      injuries, 126 aged over 60 years old accounting for 13.52% of all the patients
      (male:female, 1.74:1; mean age, 67.08 years old). Approximately 52% of the
      patients were injured by falls. The most frequently observed type of injuries was
      soft tissue injuries (100%), followed by facial fractures (83.05%). Of the
      patients with soft tissue injuries, the abrasions accounted the most, followed by
      lacerations. The numbers of patients of midface fracture (60 patients) were
      almost similar to the number of lower face fractures (66 patients). Eighty two
      patients (65.08%%) demonstrated associated injuries, of which craniocerebral
      injuries were the most prevalent. One hundred and four patients (82.54%) had
      other systemic medical conditions, with cardiovascular diseases the most and
      followed by metabolic diseases and musculoskeletal conditions. Furthermore, the
      study indicated a relationship between maxillofacial fractures and
      musculoskeletal conditions. Only 13 patients (10.32%) sustained local infections,
      of whom had other medical conditions. Most of the facial injuries (85.71%) in
      older people were operated including debridement, fixing loose teeth, reduction,
      intermaxillary fixation and open reduction and internal fixation (ORIF).
      CONCLUSIONS: Our analysis of the characteristics of maxillofacial injuries in the
      elder patents may help to promote clinical research to develop more effective
      treatment and possibly prevent such injuries.

PMID- 25858087
TI  - Drilling dimension effects in early stages of osseointegration and implant
      stability in a canine model.
AB  - BACKGROUND: This study histologically evaluated two implant designs: a classic
      thread design versus another specifically designed for healing chamber formation
      placed with two drilling protocols. STUDY DESIGN: Forty dental implants (4.1 mm
      diameter) with two different macrogeometries were inserted in the tibia of 10
      Beagle dogs, and maximum insertion torque was recorded. Drilling techniques were:
      until 3.75 mm (regular-group); and until 4.0 mm diameter (overdrilling-group) for
      both implant designs. At 2 and 4 weeks, samples were retrieved and processed for
      histomorphometric analysis. For torque and BIC (bone-to-implant contact) and BAFO
      (bone area fraction occupied), a general-linear model was employed including
      instrumentation technique and time in vivo as independent. RESULTS: The insertion
      torque recorded for each implant design and drilling group significantly
      decreased as a function of increasing drilling diameter for both implant designs
      (p<0.001). No significant differences were detected between implant designs for
      each drilling technique (p>0.18). A significant increase in BIC was observed from
      2 to 4 weeks for both implants placed with the overdrilling technique (p<0.03)
      only, but not for those placed in the 3.75 mm drilling sites (p>0.32).
      CONCLUSIONS: Despite the differences between implant designs and drilling
      technique an intramembranous-like healing mode with newly formed woven bone
      prevailed.

PMID- 25858088
TI  - Magnetic interaction between a radical spin and a single-molecule magnet in a
      molecular spin-valve.
AB  - Molecular spintronics using single molecule magnets (SMMs) is a fast growing
      field of nanoscience that proposes to manipulate the magnetic and quantum
      information stored in these molecules. Herein we report evidence of a strong
      magnetic coupling between a metallic ion and a radical spin in one of the most
      extensively studied SMMs: the bis(phtalocyaninato)terbium(III) complex (TbPc2).
      For that we use an original multiterminal device comprising a carbon nanotube
      laterally coupled to the SMMs. The current through the device, sensitive to
      magnetic interactions, is used to probe the magnetization of a single Tb ion.
      Combining this electronic read-out with the transverse field technique has
      allowed us to measure the interaction between the terbium ion, its nuclear spin,
      and a single electron located on the phtalocyanine ligands. We show that the
      coupling between the Tb and this radical is strong enough to give extra
      resonances in the hysteresis loop that are not observed in the anionic form of
      the complex. The experimental results are then modeled by diagonalization of a
      three-spins Hamiltonian. This strong coupling offers perspectives for
      implementing nuclear and electron spin resonance techniques to perform basic
      quantum operations in TbPc2. 

PMID- 25858089
TI  - The roles of RgpB and Kgp in late onset gingipain activity in the vimA-defective
      mutant of Porphyromonas gingivalis W83.
AB  - Previous studies have shown that VimA, an acetyltransferase, can modulate
      gingipain biogenesis in Porphyromonas gingivalis. Inactivation of the vimA gene
      resulted in isogenic mutants that showed a late onset of gingipain activity that
      only occurred during the stationary growth phase. To further elucidate the role
      and contribution of the gingipains in this VimA-dependent process, isogenic
      mutants defective in the gingipain genes in the vimA-deficient genetic background
      were evaluated. In contrast with the wild-type strain, RgpB and Kgp gingipain
      activities were absent in exponential phase in the ?rgpA::tetQ-vimA::ermF mutant.
      However, these activities increased to 31 and 53%, respectively, of that of the
      wild-type during stationary phase. In the ?rgpA::cat-?kgp::tetQ-vimA::ermF
      mutant, the RgpB protein was observed in the extracellular fraction but no
      activity was present even at the stationary growth phase. There was no gingipain
      activity observed in the ?rgpB::cat-?kgp::tetQ-vimA::ermF mutant whereas Kgp
      activity in ?rgpA::cat-?rgpB::tetQ-vimA::ermF mutant was 24% of the wild-type at
      late stationary phase. In contrast to RgpA, the glycosylation profile of the RgpB
      catalytic domain from both W83 and P. gingivalis FLL92 (vimA::ermF) showed
      similarity. Taken together, the results suggest multiple gingipain activation
      pathways in P. gingivalis. Whereas the maturation pathways for RgpA and RgpB are
      different, the late-onset gingipain activity in the vimA-defective mutant was due
      to activation/maturation of RgpB and Kgp. Moreover, unlike RgpA, which is VimA
      dependent, the maturation/activation pathways for RgpB and Kgp are interdependent
      in the absence VimA.

PMID- 25858090
TI  - Multiplex real-time PCR monitoring of intestinal helminths in humans reveals
      widespread polyparasitism in Northern Samar, the Philippines.
AB  - The global socioeconomic importance of helminth parasitic disease is underpinned
      by the considerable clinical impact on millions of people. While helminth
      polyparasitism is considered common in the Philippines, little has been done to
      survey its extent in endemic communities. High morphological similarity of eggs
      between related species complicates conventional microscopic diagnostic methods
      which are known to lack sensitivity, particularly in low intensity infections.
      Multiplex quantitative PCR diagnostic methods can provide rapid, simultaneous
      identification of multiple helminth species from a single stool sample. We
      describe a multiplex assay for the differentiation of Ascaris lumbricoides,
      Necator americanus, Ancylostoma, Taenia saginata and Taenia solium, building on
      our previously published findings for Schistosoma japonicum. Of 545 human faecal
      samples examined, 46.6% were positive for at least three different parasite
      species. High prevalences of S. japonicum (90.64%), A. lumbricoides (58.17%), T.
      saginata (42.57%) and A. duodenale (48.07%) were recorded. Neither T. solium nor
      N. americanus were found to be present. The utility of molecular diagnostic
      methods for monitoring helminth parasite prevalence provides new information on
      the extent of polyparasitism in the Philippines municipality of Palapag. These
      methods and findings have potential global implications for the monitoring of
      neglected tropical diseases and control measures. 

PMID- 25858091
TI  - Identification and characterisation of Emp53, the homologue of human tumor
      suppressor p53, from Echinococcus multilocularis: its role in apoptosis and the
      oxidative stress response.
AB  - Larvae of the fox tapeworm, Echinococcus multilocularis, cause alveolar
      echinococcosis, which is considered to be the most lethal helminthic infection in
      humans. Since it develops in host organs, the parasite must have evolved a stress
      defense system to cope with various genotoxic and cellular stresses that may
      cause DNA damage and genomic instability. Tumor suppressor p53, well known as the
      "guardian of the genome", plays a vital role in response to many types of stress
      and damage. In the present study, we describe the characterisation of Emp53 from
      E. multilocularis and demonstrate that it is a structural and functional
      homologue of mammalian tumor suppressor p53. We show that Emp53 binds
      specifically to oligonucleotides containing conventional p53 binding sites,
      indicating that it exhibits a function as a DNA binding transcription factor.
      Inhibition of Emp53 function can suppress UV irradiation-induced apoptosis in the
      E. multilocularis metacestode, indicating an important role of Emp53 in the
      induction of apoptosis following DNA damage. We also reveal that Emp53 plays
      important roles in resistance to oxidative stress and regulation of oxidative
      stress-induced apoptosis. Our results suggest that, similar to its human
      counterpart, Emp53 plays a central role in the network of DNA damage responses
      and apoptosis in E. multilocularis. These results may help in exploring stress
      defense mechanisms of parasitic helminths and may provide useful information for
      the development of new interventions and therapeutic drugs for the control of
      alveolar echinococcosis. 

PMID- 25858092
TI  - Battle of the sexes over paternity.
AB  - Reproductive behaviors have evolved through severe inter-sexual competition. We
      have recently described a behavior in post-mated female Drosophila melanogaster
      that controls ejaculate retention and sperm storage, and is a possible mechanism
      by which females who have mated with several partners can choose which sperm that
      is stored and used for fertilization. This behavior can also regulate exposure of
      the female to harmful effects of male SFP that are present in the ejaculate. Our
      study identified the neural pathway functioning in the female brain that
      regulates this behavior.

PMID- 25858093
TI  - The serine threonine kinase RIP3: lost and found.
AB  - Receptor-interacting protein kinase-3 (RIP3, or RIPK3) is an essential protein in
      the "programmed", or "regulated" necrosis cell death pathway that is activated in
      response to death receptor ligands and other types of cellular stress. Programmed
      necrotic cell death is distinguished from its apoptotic counterpart in that it is
      not characterized by the activation of caspases; unlike apoptosis, programmed
      necrosis results in plasma membrane rupture, thus spilling the contents of the
      cell and triggering the activation of the immune system and inflammation. Here we
      discuss findings, including our own recent data, which show that RIP3 protein
      expression is absent in many cancer cell lines. The recent data suggests that the
      lack of RIP3 expression in a majority of these deficient cell lines is due to
      methylation-dependent silencing, which limits the responses of these cells to pro
      necrotic stimuli. Importantly, RIP3 expression may be restored in many cancer
      cells through the use of hypomethylating agents, such as decitabine. The
      potential implications of loss of RIP3 expression in cancer are explored, along
      with possible consequences for chemotherapeutic response.

PMID- 25858095
TI  - Effect of emotional arousal on inter-temporal decision-making: an fMRI study.
AB  - BACKGROUND: Previous research has shown that emotion can significantly impact
      decision-making in humans. The current study examined whether or not and how
      situationally induced emotion influences people to make inter-temporal choices.
      METHODS: Affective pictures were used as experiment stimuli to provoke emotion,
      immediately followed by subjects' performance of a delay-discounting task to
      measure impulsivity during functional magnetic resonance imaging. RESULTS:
      Results demonstrate a subsequent process of increased impulsive decision-making
      following a prior exposure to both high positive and negative arousal stimuli,
      compared to the experiment subjects' experiences with neutral stimuli. Findings
      indicate that increased impulsive decision-making behaviors can occur with high
      arousal and can be characterized by decreased activities in the cognitive control
      regions such as prefronto-parietal regions. CONCLUSIONS: These results suggest
      that 'stabilization of high emotional arousal' may facilitate a reduction of
      impulsive decision-making and implementation of longer term goals.

PMID- 25858096
TI  - Appendiceal phlegmon mimicking intussusception on ultrasound: correspondence
      between sonographic and operative findings.
AB  - Little is known about the possibility that ruptured appendicitis may produce a
      false sonographic appearance of intussusception. We present here a case of a
      periappendiceal phlegmon mimicking ileocolic intussusception on ultrasound in a
      3.5-year-old girl and provide a surgico-anatomic explanation on the basis of the
      intraoperative findings for the false sonographic image. CT imaging was used to
      make the diagnosis. Intraoperatively, it was revealed that the cecum and sigmoid,
      which were adherent to each other with pseudomembranes, formed an intestinal mass
      around the appendix. Accordingly, the appendicolith at the center of the phlegmon
      was responsible for the central echogenicity, and the surrounding cecum and
      sigmoid for the external hypoechoic and hyperechoic rings of the target-sign
      appearing mass on the preoperative ultrasound. Such an understanding of the
      etiology of the false sonographic image may help to increase awareness and avoid
      misdiagnosis.

PMID- 25858097
TI  - Sacral nerve stimulation: a promising therapy for fecal and urinary incontinence
      and constipation in children.
AB  - PURPOSE: This study describes our series of children with bowel and bladder
      dysfunction (BDD) treated with sacral nerve stimulation in order to begin to
      identify characteristics associated with better outcomes and guide future
      therapies. METHODS: Between May 2012 and February 2014, 29 patients were
      evaluated before and after sacral nerve stimulator (SNS) placement. A prospective
      data registry was developed that contains clinical information and patient
      reported measures: Fecal Incontinence Qualify of Life Scale, Fecal Incontinence
      Severity Scale, PedsQL Gastrointestinal Symptom Scale, and Vancouver DES Symptom
      Scale. RESULTS: The median age of patients was 12.1 (interquartile range: 9.4,
      14.3) years and the median follow-up period was 17.7 (12.9, 36.4) weeks. 93% had
      GI complaints and 65.5% had urinary symptoms while 7% had urologic symptoms only.
      The most common etiologies of BBD were idiopathic (66%) and imperforate anus
      (27%). Five patients required reoperation due to a complication with battery
      placement. Six of 11 patients (55%) with a pre-SNS cecostomy tube no longer
      require an antegrade bowel regimen as they now have voluntary bowel movements.
      Ten of eleven patients (91%) no longer require anticholinergic medications for
      bladder overactivity after receiving SNS. Significant improvements have been
      demonstrated in all four patient-reported instruments for the overall cohort.
      CONCLUSIONS: Early results have demonstrated improvements in both GI and urinary
      function after SNS placement in pediatric patients with bowel and bladder
      dysfunction.

PMID- 25858094
TI  - Management of severe paediatric malaria in resource-limited settings.
AB  - Over 90% of the world's severe and fatal Plasmodium falciparum malaria is
      estimated to affect young children in sub-Sahara Africa, where it remains a
      common cause of hospital admission and inpatient mortality. Few children will
      ever be managed on high dependency or intensive care units and, therefore, rely
      on simple supportive treatments and parenteral anti-malarials. There has been
      some progress on defining best practice for antimalarial treatment with the
      publication of the AQUAMAT trial in 2010, involving 5,425 children at 11 centres
      across 9 African countries, showing that in artesunate-treated children, the
      relative risk of death was 22.5% (95% confidence interval (CI) 8.1 to 36.9) lower
      than in those receiving quinine. Human trials of supportive therapies carried out
      on the basis of pathophysiology studies, have so far made little progress on
      reducing mortality; despite appearing to reduce morbidity endpoints, more often
      than not they have led to an excess of adverse outcomes. This review highlights
      the spectrum of complications in African children with severe malaria, the
      therapeutic challenges of managing these in resource-poor settings and examines
      in-depth the results from clinical trials with a view to identifying the
      treatment priorities and a future research agenda. 

PMID- 25858098
TI  - Ileal pouch anal anastomosis in pediatric familial adenomatous polyposis: A 24
      year review of operative technique and patient outcomes.

PMID- 25858099
TI  - Pathologic leadpoint is uncommon in ileo-colic intussusception regardless of age.
AB  - PURPOSE: Historically, the rate of pathologic leadpoints in older children with
      intussusception is quoted as 20%-25%. Our anecdotal experience suggested a lower
      rate. We therefore compiled a case series to examine the actual incidence of
      pathologic leadpoint, and treatment success, by age. METHODS: A retrospective
      review was performed of all patients admitted with intussusception between 1998
      and 2012 and tested for differences in anatomic location, presence of pathologic
      leadpoint, and need for operative intervention, on the basis of age. RESULTS: In
      total, 154 cases of intussusception were diagnosed in 141 patients (136 ileo
      colic), 38 of which were in children older than 3 (29 ileo-colic). Considering
      all anatomic locations, older children were more likely to have a pathologic
      leadpoint (p-value 0.01); however subgroup analysis of ileo-colic intussusception
      demonstrated no difference (p-value 0.38). Additionally, there was no difference
      in the success of pneumatic or barium enema reduction on the basis of age (p
      value 0.56). CONCLUSION: Despite historical reports of increased pathologic
      leadpoints in ileo-colic intussusception in older children, in this series the
      majority were idiopathic. Non-operative management was successful approximately
      75% of the time, irrespective of age. In older age groups, there was an increased
      frequency of pathologic leadpoints in small bowel-small bowel intussusception.

PMID- 25858100
TI  - Be vigilant: New MERS-CoV outbreaks can occur in the Kingdom of Saudi Arabia.

PMID- 25858101
TI  - Role of surgical resection for refractory germ cell tumors.
AB  - PURPOSE: This article aims to critically review the current recommendations with
      regard to the role of surgery following salvage chemotherapy, growing teratoma
      syndrome, late relapse, as well as malignant transformation. METHODS: All the
      literature published in English and available on Pubmed pertaining to refractory
      germ cell tumors was reviewed and the relevant articles, as well as our own
      institutional experience were included in this review. RESULTS: There is
      universal agreement that patients with non-seminoma who have residual tumor
      measuring greater than one centimeter should undergo post-chemotherapy
      retroperitoneal lymph node dissection (PC-RPLND) for resection of potential
      teratoma or viable germ cell tumor. The role of surgical resection is less clear
      in patients who are deemed to have germ cell tumors refractory to chemotherapy.
      Patients with residual masses following second line therapy, those with growing
      teratoma, late relapse, and malignant transformation should all be considered for
      upfront surgical resection. Compared with the typical PC-RPLND, these operations
      are generally more complex, with a higher proportion requiring adjunctive
      procedures; and should be performed in experienced, tertiary referral centers.
      CONCLUSION: Patients who have complete resection of disease are sill curable and
      patients with chemorefractory disease should have evaluation by an expert
      surgeon.

PMID- 25858102
TI  - Decision analysis model comparing cost of multiparametric magnetic resonance
      imaging vs. repeat biopsy for detection of prostate cancer in men with prior
      negative findings on biopsy.
AB  - PURPOSE: We compared cost of multiparametric magnetic resonance imaging (MP-MRI)
      vs. repeat biopsy in detection of prostate cancer (PCa) in men with prior
      negative findings on biopsy. METHODS: A decision tree model compared the strategy
      of office-based transrectal ultrasound-guided biopsy (TRUS) for men with prior
      negative findings on biopsy with a strategy of initial MP-MRI with TRUS performed
      only in cases of abnormal results on imaging. Study end points were cost, number
      of biopsies, and cancers detected. Cost was based on Medicare reimbursement. Cost
      of sepsis and minor complications were incorporated into analysis. Sensitivity
      analyses were performed by varying model assumptions. RESULTS: The baseline model
      with 24% PCa found that the overall cost for 100 men was $90,400 and $87,700 for
      TRUS and MP-MRI arms, respectively. The MP-MRI arm resulted in 73 fewer biopsies
      per 100 men but detected 4 fewer cancers (16 vs. 20.4) than the TRUS arm did. A
      lower risk of PCa resulted in lower costs for the MP-MRI arm and a small
      difference in detected cancers. At lower cancer rates, MP-MRI is superior to TRUS
      over a wide range of sensitivity and specificity of MRI. A lower sensitivity of
      MP-MRI decreases the cost of the MP-MRI, as fewer biopsies are performed, but
      this also reduces the number of cancers detected. CONCLUSIONS: The use of MP-MRI
      to select patients for repeat biopsy reduced the number of biopsies needed by 73%
      but resulted in a few cancers being missed at lower cost when compared with the
      TRUS arm. Further studies are required to determine whether cancers missed
      represent clinically significant tumors.

PMID- 25858103
TI  - Neoadjuvant endocrine therapy for resectable breast cancer: A systematic review
      and meta-analysis.
AB  - INTRODUCTION: The role of neoadjuvant endocrine therapy for resectable breast
      cancer is not well established, despite encouraging results obtained in the
      metastatic and adjuvant settings. This systematic review aims to examine existing
      medical literature on neoadjuvant hormone therapy (HT). METHODS: Data from
      prospective, randomized trials was included if comparing neoadjuvant HT versus
      surgery alone without adjuvant treatment, or neoadjuvant HT versus chemotherapy
      (CT), or HT plus CT versus CT alone, or HT plus CT versus HT alone, or two
      distinct HT. Odds Ratios (OR) were calculated from pooled data. RESULTS: Five
      studies compared HT with tamoxifen versus HT with aromatase inhibitors (AI). A
      meta-analysis of their results demonstrated superiority of AIs in overall
      response rate (ORR) (OR 1.9; 95% CI 1.17-3.08). Two trials compared HT against
      CT, and pooled data from them demonstrated a trend favoring CT (OR for ORR 0.75;
      95% CI 0.35-1.6). That trend disappeared when only postmenopausal women were
      considered (OR 1.01; 95% CI 0.62-1.63). One trial compared HT plus CT with no
      neoadjuvant treatment, and obtained an 83% ORR. One trial compared HT plus CT
      versus CT alone and found a non-significant increase in ORR for adding HT to CT
      (OR 1.48; 95% CI 0.58-3.77). No trial compared HT plus CT versus HT alone.
      CONCLUSIONS: Neoadjuvant HT is a safe and feasible option, but it cannot be
      considered equivalent to CT. If neoadjuvant HT is performed, AIs are preferable
      over tamoxifen due to higher response rates.

PMID- 25858104
TI  - Regulatory and clinical aspects of psychotropic medicinal products
      bioequivalence.
AB  - Introduction of generic medicinal products to the market has increased access to
      modern therapies but also enabled significant reduction in their cost, leading to
      containment of public expenditures on medicinal products reimbursement. The
      critical assessment of bioequivalence of any reference medicinal product and its
      counterpart is based on comparison of their rate and extent of absorption. It is
      assumed that two medicinal products are bioequivalent when their rate and extent
      of absorption do not show significant differences when administered at the same
      dose under similar experimental conditions. Bioequivalent medicinal products are
      declared to be also therapeutically equivalent and can be used interchangeably.
      However, despite regulatory declaration, switching from reference to generic
      drugs is often associated with concerns of healthcare providers about decreased
      treatment effectiveness or occurrence of adverse drug reactions. The aim of this
      article is to provide a description of rules that guide registration of generic
      medicinal products in the European Union and to analyze specific examples from
      the scientific literature concerning therapeutic equivalence of reference and
      generic antidepressant and antipsychotic medicinal products. 

PMID- 25858105
TI  - Tunable synthesis of self-assembled cyclic peptide nanotubes and nanoparticles.
AB  - While tremendous efforts have been made in investigating scalable approaches for
      fabricating nanoparticles, less progress has been made in scalable synthesis of
      cyclic peptide nanoparticles and nanotubes, despite their great potential for
      broader biomedical applications. In this paper, tunable synthesis of self
      assembled cyclic peptide nanotubes and nanoparticles using three different
      methods, phase equilibrium, pH-driven, and pH-sensitive methods, were proposed
      and investigated. The goal is scalable nanomanufacturing of cyclic peptide
      nanoparticles and nanotubes with different sizes in large quality by controlling
      multiple process parameters. Cyclo-(L-Gln-D-Ala-L-Glu-D-Ala-)2 was applied to
      illustrate the proposed ideas. In the study, mass spectrometry and high
      performance liquid chromatography were employed to verify the chemical structures
      and purity of the cyclic peptides. Morphology and size of the synthesized
      nanomaterials were characterized using atomic force microscopy and dynamic light
      scattering. The dimensions of the self-assembled nanostructures were found to be
      strongly influenced by the cyclic peptide concentration, side chain modification,
      pH values, reaction time, stirring intensity, and sonication time. This paper
      proposed an overall strategy to integrate all the parameters to achieve optimal
      synthesis outputs. Mechanisms of the self-assembly of the cyclic peptide
      nanotubes and nanoparticles under variable conditions and tunable parameters were
      discussed. This study contributes to scalable nanomanufacturing of cyclic peptide
      based self-assembled nanoparticles and nanotubes for broader biomedical
      applications.

PMID- 25858106
TI  - Field Research and Parametric Analysis in a Medical-Surgical Unit.
AB  - OBJECTIVE: To study the workplace in a medical-surgical (med-surg) unit and to
      identify suboptimal environmental conditions that can be improved in the current
      unit and avoided in future design, through rapidly deployed field research and
      timely simulation. BACKGROUND: Literature emphasizes the importance of the
      healthcare workplace and the effect on patient outcomes. What is lacking are
      studies conducted on-site and used for immediate application in design to assess
      and improve workplace conditions. METHODS: A rapidly deployed field research and
      simulation study was conducted in a 40-bed med-surg unit of a large healthcare
      system as part of the process of designing a new medical tower. Online surveys,
      systematic behavioral observations, semi-structured interviews, sound studies,
      and advanced spatial analysis through parametric modeling were conducted.
      RESULTS: The following created challenges for patient monitoring, care
      coordination, and management: (1) waste and variability in walking, (2) limited
      point-of-use access to supplies, (3) large distances traveled for minor tasks,
      and (4) low visibility and connectivity. The corridor is used as a
      workspace/communication hub. There is a distinct difference in beginning of day
      and night shift patterns and between walking "distance" and walking "sequence."
      There is a tendency for nurses to multitask, but a simulation exercise shows that
      for key tasks like medication delivery, multitasking may not always reduce
      walking distances. CONCLUSION: Co-location of medications, supplies, and
      nourishment; accommodation for work on wheels; and spatial and technological
      connectivity between care team and patients should be considered while designing
      a med-surg unit. Understanding the key activity sequences helps determine the
      proximity of spaces in relationship to patient rooms and each other.

PMID- 25858107
TI  - Screening of antimicrobial, antioxidant properties and bioactive compounds of
      some edible mushrooms cultivated in Bangladesh.
AB  - BACKGROUND: For a long time mushrooms have been playing an important role in
      several aspects of the human activity. Recently edible mushrooms are used
      extensively in cooking and make part of new food in Bangladesh for their
      beneficial properties. The aim of this study is to screen some values of
      mushrooms used in Bangladesh. METHODS: Methanolic extracts of 3 edible mushrooms
      (Pleurotus ostreatus, Lentinula edodes, Hypsizigus tessulatus) isolated from
      Chittagong, Bangladesh were used in this study. Phenolic compounds in the
      mushroom methanolic extracts were estimated by a colorimetric assay. The
      antioxidant activity was determined by radical 1, 1-diphenyl;-2-picrylhydrazyl
      (DPPH) radical scavenging assay. Eight microbial isolates were used for
      antimicrobial activity of methanolic extract of mushrooms by the agar well
      diffusion method with slight modification. RESULTS: Determination of
      antimicrobial activity indicated considerable activity against all bacteria and
      fungi reveling zone of inhibition ranged from 7 +/- 0.2 to 20 +/- 0.1 mm. Minimum
      inhibitory concentration values of the extracts showed that they are also active
      even in least concentrations ranged from 1 mg/ml to 9 mg/ml. Lentinula edodes
      showed the best antimicrobial activity than others. Pseudomonas aeruginosa was
      quite resistant and Saccharomyces cerevisiae was more sensitive than others
      microbial isolates. Antioxidant efficiency by inhibitory concentration on 1,1
      Diphenly-2-picrylhydrazyl (DPPH) was found significant when compared to standard
      antioxidant like ascorbic Acid . The concentration (IC50) ranged from 100 +/-
      1.20 to 110 +/- 1.24 MUg/ml. Total phenols are the major bioactive component
      found in extracts of isolates expressed as mg of GAE per gram of fruit body,
      which ranged from 3.20 +/- 0.05 to 10.66 +/- 0.52 mg/ml. Average concentration of
      flavonoid ranged from 2.50 +/- 0.008 mg/ml to 4.76 +/- 0.11 mg/ml; followed by
      very small concentration of ascorbic acid (range, 0.06 +/- 0.00 mg/ml to 0.21 +/-
      0.01 mg/ml) in all the isolates. All the isolates showed high phenol and
      flavonoid content (except Pleurotus ostreatus), but ascorbic acid content was
      found in traces. CONCLUSION: This study has revealed that selected edible
      mushrooms have not only nutritional values but also some therapeutic values.
      Proper and more investigations can lead us to use these as strong medicine in
      future.

PMID- 25858108
TI  - Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels regulate
      firing of globus pallidus neurons in vivo.
AB  - The globus pallidus plays a significant role in motor control under both health
      and pathological states. Recent studies have revealed that hyperpolarization
      activated cyclic nucleotide-gated (HCN) channels occupy a critical position in
      globus pallidus pacemaking activity. Morphological studies have shown the
      expression of HCN channels in the globus pallidus. To investigate the in vivo
      effects of HCN channels in the globus pallidus, extracellular recordings and
      behavioral tests were performed in the present study. In normal rats, micro
      pressure ejection of 0.05mM ZD7288, the selective HCN channel blocker, decreased
      the frequency of spontaneous firing in 21 out of the 40 pallidal neurons. The
      average decrease was 50.4+/-5.4%. Interestingly, in another 18 out of the 40
      pallidal neurons, ZD7288 increased the firing rate by 137.1+/-27.6%. Similar
      bidirectional modulation on the firing rate was observed by a higher
      concentration of ZD7288 (0.5mM) as well as another HCN channel blocker, CsCl.
      Furthermore, activation of HCN channels by 8-Br-cAMP increased the firing rate by
      63.0+/-9.3% in 15 out of the 25 pallidal neurons and decreased the firing rate by
      46.9+/-9.4% in another 8 out of the 25 pallidal neurons. Further experiments
      revealed that modulation of glutamatergic but not GABAergic transmission may be
      involved in ZD7288-induced increase in firing rate. Consistent with
      electrophysiological results, further studies revealed that modulation of HCN
      channels also had bidirectional effects on behavior. Taken together, the present
      studies suggest that HCN channels may modulate the activity of pallidal neurons
      by different pathways in vivo. 

PMID- 25858109
TI  - Pore forming activity of the potent RTX-toxin produced by pediatric pathogen
      Kingella kingae: Characterization and comparison to other RTX-family members.
AB  - Pediatric septic arthritis in patients under age of four is frequently caused by
      the oral Gram-negative bacterium Kingella kingae. This organism may be
      responsible for a severe form of infective endocarditis in otherwise healthy
      children and adults. A major virulence factor of K. kingae is RtxA, a toxin that
      belongs to the RTX (Repeats-in-ToXin) group of secreted pore forming toxins. To
      understand the RtxA effects on host cell membranes, the toxin activity was
      studied using planar lipid bilayers. K. kingae strain PYKK081 and its isogenic
      RtxA-deficient strain, KKNB100, were tested for their ability to form pores in
      artificial membranes of asolectin/n-decane. RtxA, purified from PYKK081, was able
      to rapidly form pores with an apparent diameter of 1.9nm as measured by the
      partition of nonelectrolytes in the pores. The RtxA channels are cation-selective
      and showed strong voltage-dependent gating. In contrast to supernatants of
      PYKK081, those of KKNB100 did not show any pore forming activity. We concluded
      that RtxA toxin is the only secreted protein from K. kingae forming large
      channels in host cell membranes where it induces cation flux leading to
      programmed cell death. Furthermore, our findings suggested that the planar lipid
      bilayer technique can effectively be used to test possible inhibitors of RTX
      toxin activity and to investigate the mechanism of the toxin binding to the
      membrane. 

PMID- 25858110
TI  - Electrochemical analysis of autodisplayed adrenodoxin (Adx) on the outer membrane
      of E. coli.
AB  - In this work, adrenodoxin (Adx) was expressed on the outer membrane of E. coli by
      autodisplay and then the iron-sulfur cluster was incorporated into apo-Adx by an
      anaerobic reconstitution process. For the determination of the redox potentials
      of the iron-sulfur clusters of the autodisplayed Adx, E. coli cells with
      autodisplayed Adx were immobilized on a gold electrode modified with a self
      assembled monolayer of mercaptoundecanoic acid (MUA). From the repeated cyclic
      voltammetry (CV) analysis, the E. coli (10mM HEPES buffer, pH7.0) with
      autodisplayed Adx showed significant changes in shape with an oxidation peak at
      +0.4V (vs. Ag/AgCl) and a reduction peak at -0.3V (vs. Ag/AgCl) after the
      reconstitution process for the incorporation of the iron-sulfur cluster. From the
      repeated CV analysis in the reduction and oxidation potential ranges, the iron
      sulfur clusters of the autodisplayed Adx were observed to undergo reversible
      redox reactions via direct electron transfer to the MUA-modified gold electrode. 

PMID- 25858111
TI  - The structure-function role of C-terminus in human bitter taste receptor T2R4
      signaling.
AB  - Bitter taste, in humans, is sensed by 25 G protein-coupled receptors, referred to
      as bitter taste receptors (T2Rs). The diverse roles of T2Rs in various extraoral
      tissues have implicated them as a potential target for therapeutic intervention.
      Structure-function studies have provided insights into the role of transmembrane
      and loop regions in the activation mechanism of T2Rs. However, studies aimed at
      deciphering the role of their carboxyl-terminus (C-terminus) are limited. In this
      study, we identified a KLK/R motif in the C-terminus that is conserved in 19 of
      the 25 T2Rs. Using site-directed mutagenesis we studied the role of 16 residues
      in the C-terminus of T2R4. The C-terminus of T2R4 is polybasic with 6 of the 16
      residues consisting of lysines, constituting two separate KK motifs. We analyzed
      the effect of the C-terminus mutations on plasma membrane trafficking, and
      characterized their function in response to the T2R4 agonist quinine. The
      majority of the mutants showed defective receptor trafficking with <=50%
      expression on the cell surface. Interestingly, mutation of the distal Lys296 of
      the KLK motif in T2R4 resulted in constitutive activity. The K296A mutant
      displayed five-fold basal activity over wild type T2R4, while the conservative
      substitution K296R showed wild type characteristics. The Lys294, Leu295 and
      Lys296 of the KLK motif in T2R4 were found to perform crucial roles, both, in
      receptor trafficking and function. Results from this study provide unique
      mechanistic insights into the structure-function role of the C-terminus in T2R
      signaling. 

PMID- 25858112
TI  - Povidone iodine skin absorption: an ex-vivo study.
AB  - Povidone iodine is a water-soluble complex used to disinfect the skin surface and
      it exerts prolonged germicidal action against a broad spectrum of germs. Indeed,
      it is often applied on burned skin, large wounds, deep tissues or mucosa. Notably
      some surgical hand-scrub solutions, which are considered safe antiseptics,
      contain large amounts of iodine that can be absorbed by skin. The aim of present
      study was to study the skin absorption of iodine after the application on the
      skin of povidone-iodine solution, used by health care workers during surgical
      procedure. We use Franz diffusion static cells with human skin. After 24h from
      the beginning of our measurement the iodine concentration in the receiving
      compartment was 11.59+/-6.3MUg/cm(2). The medium flux calculated was 0.73+/
      0.33MUg/cm(2)/h with a lag time of 8.9+/-1.5h. These in vitro results confirmed
      that povidone iodine could pass through the skin in a relevant amount that can
      explain the clinical findings in burned or surgically treated patients. In
      professional use the repetitive contact with povidone iodine, also as soap, can
      cause iodine skin permeation that must be considered when the washing procedures
      are repeated more than 20 times a day.

PMID- 25858113
TI  - Cytochrome P450-derived versus mitochondrial oxidant stress in acetaminophen
      hepatotoxicity.
AB  - In evaluating the mechanisms of acetaminophen hepatotoxicity in experimental
      systems, it is critical to keep in mind the relevance of the model system for
      humans. Important aspects of the human toxicity include formation of a reactive
      metabolite by the cytochrome P450 system and protein adduct formation, which is
      thought to trigger mitochondrial dysfunction and oxidant stress ultimately
      causing necrotic cell death. If models that miss critical parts of this well
      established mechanism are used, the relevance of the new information for the
      human toxicity has to be questioned. Therefore, we feel it is necessary to
      express our concern regarding the recent publication by Jiang et al. (2015). 

PMID- 25858114
TI  - Occurrence of Aelurostrongylus abstrusus (Railliet, 1898) in Danish cats: A
      modified lung digestion method for isolating adult worms.
AB  - As Aelurostrongylus abstrusus has not previously received any attention in
      Denmark, the study investigated the occurrence of A. abstrusus amongst outdoor
      cats from three regions (Zealand, Mon and Falster). Faeces and lungs were
      collected from a total of 147 feral (n=125) and domesticated cats (n=22) that
      were euthanized for reasons outside of this project. Using a modified Baermann
      technique 13.6% of the cats was found to be positive. A new lung digestion
      technique was developed to isolate eggs, L1 and adult worms from the lungs and
      this revealed a prevalence of 15.6% although with regional differences. There was
      no difference between feral and domesticated cats just as sex and age did not
      appear to influence prevalence and worm burden. Lungs from 87% of the positive
      cats had the gross appearance compatible with A. abstrusus and the severity of
      lung damage was proportional to LPG and number of adult worms. Within the current
      range of worm burdens (0-22) with a mean intensity of 7 per cat, there was a
      correlation with faecal excretion levels of L1 that ranged from 0-39,000 with a
      mean of 3586 per cat. The results did not indicate that the infection levels of
      the naturally infected cats were substantially affected by acquired immunity, but
      further studies are needed to determine the importance of host immune responses
      in regulating parasite populations. 

PMID- 25858115
TI  - The epidemiology of tick-borne haemoparasites as determined by the reverse line
      blot hybridization assay in an intensively studied cohort of calves in western
      Kenya.
AB  - The development of sensitive surveillance technologies using PCR-based detection
      of microbial DNA, such as the reverse line blot assay, can facilitate the
      gathering of epidemiological information on tick-borne diseases, which continue
      to hamper the productivity of livestock in many parts of Africa and elsewhere. We
      have employed a reverse line blot assay to detect the prevalence of tick-borne
      parasites in an intensively studied cohort of indigenous calves in western Kenya.
      The calves were recruited close to birth and monitored for the presence of
      infectious disease for up to 51 weeks. The final visit samples from 453 calves
      which survived for the study period were analyzed by RLB. The results indicated
      high prevalences of Theileria mutans (71.6%), T. velifera (62.8%), Anaplasma sp.
      Omatjenne (42.7%), A. bovis (39.9%), Theileria sp. (sable) (32.7%), T. parva
      (12.9%) and T. taurotragi (8.5%), with minor occurrences of eight other
      haemoparasites. The unexpectedly low prevalence of the pathogenic species
      Ehrlichia ruminantium was confirmed by a species-specific PCR targeting the pCS20
      gene region. Coinfection analyses of the seven most prevalent haemoparasites
      indicated that they were present as coinfections in over 90% of the cases. The
      analyses revealed significant associations between several of the Theileria
      parasites, in particular T. velifera with Theileria sp. sable and T. mutans, and
      T. parva with T. taurotragi. There was very little coinfection of the two most
      common Anaplasma species, although they were commonly detected as coinfections
      with the Theileria parasites. The comparison of reverse line blot and serological
      results for four haemoparasites (T. parva, T. mutans, A. marginale and B.
      bigemina) indicated that, except for the mostly benign T. mutans, indigenous
      cattle seem capable of clearing infections of the three other, pathogenic
      parasites to below detectable levels. Although the study site was located across
      four agroecological zones, there was little restriction of the parasites to
      particular zones. 

PMID- 25858116
TI  - Detection of a quantitative trait locus associated with resistance to infection
      with Trichuris suis in pigs.
AB  - Whipworms (Trichuris spp.) infect a variety of hosts, including domestic animals
      and humans. Of considerable interest is the porcine whipworm, T. suis, which is
      particularly prevalent in outdoor production systems. High infection levels may
      cause growth retardation, anaemia and haemorrhagic diarrhoea. A significant
      proportion of the variation in Trichuris faecal egg count (FEC) has been
      attributed to the host's genetic make-up. The aim of the present study was to
      identify genetic loci associated with resistance to T. suis in pigs. We used
      single nucleotide polymorphism (SNP) markers to perform a whole-genome scan of an
      F1 resource population (n = 195) trickle-infected with T. suis. A measured
      genotype analysis revealed a putative quantitative trait locus (QTL) for T. suis
      FEC on chromosome 13 covering ~ 4.5 Mbp, although none of the SNPs reached genome
      wide significance. We tested the hypothesis that this region of SSC13 harboured
      genes with effects on T. suis burden by genotyping three SNPs within the putative
      QTL in unrelated pigs exposed to either experimental or natural T. suis
      infections and from which we had FEC (n = 113) or worm counts (n = 178). In these
      studies, two of the SNPs (rs55618716, ST) were associated with FEC (P < 0.01),
      thus confirming our initial findings. However, we did not find any of the SNPs to
      be associated with T. suis worm burden. In conclusion, our study demonstrates
      that genetic markers for resistance to T. suis as indicated by low FEC can be
      identified in pigs.

PMID- 25858117
TI  - Combining Sprague-Dawley rat uterus cell membrane chromatography with HPLC/MS to
      screen active components from Leonurus artemisia.
AB  - CONTEXT: Leonurus artemisia (Lour.) S.Y.Hu (Lamiaceae) (YiMuCao in Chinese) is a
      traditional Chinese medicine. Leonurus artemisia has been shown to have many
      pharmacological effects such as increasing uterine contraction amplitude, and
      tension, but the active components are still unknown. OBJECTIVE: The objective of
      this study is to determine active components of L. Artemisia that are responsible
      for the biological activity using HPLC and cell membrane-based system. MATERIALS
      AND METHODS: The whole L. artemisia ethanol extract and its eight fractions were
      screened using Sprague-Dawley rat uterus cell membrane chromatography (CMC)
      combined with the HPLC/MS system. Oxytocin was used to investigate the activity
      of CMC column. The effect of active components screened from L. artemisia was
      studied by tension measurement of isolated rat uterine strips in vitro at a dose
      of 10(-7)-10(-4 )mol/L with oxytocin as a control. RESULTS: The acetone extract
      showed obvious activity when compared with the eight extracts of L. artemisia.
      From the acetone extract, in the negative ionization mode, the active compound
      was identified as genkwanin, with a molecular weight of 283. In vitro
      pharmacological experiments proved that genkwanin promoted uterine contractions
      at a dose from 10(-7) to 10(-4 )mol/L. The EC50 value was 4.86 +/- 4.21 MUmol/L
      for genkwanin and 4.30 +/- 3.65 MUmol/L for oxytocin on the contractile amplitude
      of uterine strips isolated from rats. DISCUSSION AND CONCLUSION: Genkwanin was
      identified as the active compound in L. artemisia by this method. In vitro
      pharmacological experiments proved that genkwanin promoted uterine contractions.
      Genkwanin may be used to uterine inertia and may have an effect on postpartum
      hemorrhage.

PMID- 25858118
TI  - International trades, local spread and viral evolution: the case of porcine
      circovirus type 2 (PCV2) strains heterogeneity in Italy.
AB  - Porcine circovirus type 2 is one of the most widespread and economically relevant
      infections of swine. Four genotypes have been recognized, but currently, only
      three (PCV2a, PCV2b and PCV2d) are effectively circulating. The widespread
      livestock trade and rapid viral evolution have contributed to determining the
      high heterogeneity of PCV2 and the dispersal of potentially more virulent
      strains. Italian swine farming and the related processing industry are relevant
      in the national economy. Despite the noteworthy losses associated with direct and
      control measure costs, no data are currently available on the molecular
      epidemiology of PCV2 in Italy. Our study, which was intended to fill this gap,
      considered 75 completed genome PCV2 sequences, which were obtained from samples
      collected from the highly densely populated area of Northern Italy between 2007
      and 2014. Phylogenetic analysis and comparison with reference sequences
      demonstrated the co-circulation, with different prevalences, of PCV2a, PCV2b and
      PCV2d within the national borders, with PCV2b being the most prevalent.
      Recombination between different genotypes was also proven to be frequent.
      Phylogeographic analysis demonstrated that the marked variability of Italian PCV2
      strains can be attributable to multiple introduction events. The comparison of
      the phylogenetic analysis results, the location of different haplotypes and the
      international commercial routs of live pigs allow the speculation of several
      links as well as the role of Italy as both an importer and exporter of PCV2
      haplotypes, mainly from and to European and Asian countries. A similarly
      intricate contact network was demonstrated within national borders, with
      different haplotypes being detected in the same province and different provinces
      harbouring the same haplotype. Overall, this paper represents the first
      description of PCV2 in Italy and demonstrates that the high variability of
      circulating Italian strains is due to multiple introduction events, wide
      circulation within national boundaries and rapid viral evolution.

PMID- 25858119
TI  - The repeated introduction of the H3N2 virus from human to swine during 1979-1993
      in China.
AB  - Limited data are available regarding the swine influenza viruses (SIVs) that
      circulated in Mainland China prior to the 1990s. Eleven H3N2 virus strains were
      isolated from swine populations from 1979 to 1992. To determine the origin and
      tendency of these SIVs, the phylogenetic and antigenic properties of these
      viruses were analyzed based on the whole genome sequenced and the HI titrations
      with post-infection ferret antisera against influenza A (H3N2) virus isolates of
      swine and human origin. The results revealed that these 11 SIVs originated from
      humans and were not maintained in swine populations, indicating the interspecies
      transmission from humans to pigs occurred frequently and independently throughout
      these periods. However, human H3N2 viruses might not have the ability to
      circulate in pig herds. 

PMID- 25858120
TI  - The distribution of parasite strains among hosts affects disease spread in a
      social insect.
AB  - Social insects present highly interesting and experimentally amenable systems for
      the study of disease transmission because they naturally live in dense groups of
      frequently interacting individuals. Using experimental inoculations of five
      trypanosomatid strains into groups of its natural host, the bumblebee Bombus
      terrestris, we investigate the effects of the initial parasite strain
      distribution across group members on the establishment and transmission success
      of the different strains to new hosts. For a given number of parasite strains
      circulating within a host group, transmission to new hosts was increased when the
      strains were initially inoculated as mixed infections (as opposed to separate
      single infections), presumably because mixed infections generally favored fast
      replicating strains. In contrast, separate single infections reduced transmission
      at least in part through a precedence effect, whereby weak strains appeared to
      persist by making their host unavailable to superinfection. These results suggest
      that host groups could benefit from 'compartmentalizing' infections by different
      parasite strains across different group members, which might be achieved in
      social insects, for example, by division of labor.

PMID- 25858121
TI  - Natural hybridization of the ticks Ixodes persulcatus and Ixodes pavlovskyi in
      their sympatric populations in Western Siberia.
AB  - Hybridization of ticks of the genus Ixodes has been described for several species
      under laboratory conditions although no molecular genetics evidence confirming
      interspecific hybridization in nature is available. We have designed a real time
      PCR targeted on nuclear (ITS2) and mitochondrial (cox1) markers to accurately
      identify tick species and to detect interspecific hybrids of Ixodes persulcatus
      and Ixodes pavlovskyi in their sympatric populations in Western Siberia. A survey
      of 783 individual ticks from a suburb of Tomsk showed that 44.2% of ticks belong
      to I. pavlovskyi species and 55.8% to I. persulcatus, based on the mtDNA data.
      Results obtained with the nuclear marker were not consistent, indicating that
      approximately 10% of the ticks were hybrids and about 5% revealed mtDNA
      introgression. Both hybridization and introgression have been shown to occur
      bidirectionally but more efficiently in the mating pair female I. pavlovskyi*male
      I. persulcatus than vice versa. The existence of the first generation hybrids and
      backcrosses challenges the existing view about effective reproductive barriers
      between I. pavlovskyi and I. persulcatus. While using only mitochondrial markers
      can lead to errors in determining tick species, we propose to use nuclear or both
      markers instead. The results obtained in the present paper and published earlier
      suggest that hybridization between closely related tick species in their
      sympatric zones is common rather than exceptional. The role of hybrid populations
      of vectors in the evolution of transmitted pathogens is also discussed.

PMID- 25858122
TI  - Significance of viral status on prognosis of hepatitis B-related hepatocellular
      carcinoma after curative resection in East Asia.
AB  - Tumor recurrence remains one major obstacle for further improving the prognosis
      of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients after
      curative liver resection. It has been widely reported that tumor size, positive
      surgical margin, macroscopic vascular invasion, tumor-node-metastasis stage and
      Edmondson's grade were significantly related to HCC recurrence. However, the
      association between HCC recurrence and important viral factors, including the HBV
      DNA levels, status of hepatitis B surface antigen and hepatitis B e-antigen,
      levels of cccDNA and hepatitis B core-related antigen, viral genotypes and
      specific viral sequence mutations remained controversial. Meanwhile, studies on
      the effect of postoperative adjuvant antiviral therapy on HCC recurrence have
      been relatively limited and have yielded conflicting results. Identification of
      certain viral risk factors for HCC recurrence and stratification of patient risk
      are very important to perform future surveillance programs. As a HBV hyperendemic
      region, the majority of HBV-related HCC patients develop in East Asia. In this
      article, we thus systematically reviewed the risk of important viral factors
      involved in recurrent carcinogenesis and the role of adjuvant antiviral therapy
      in preventing tumor recurrence in this area. 

PMID- 25858123
TI  - Randomised controlled trials do not always give the results we want but that
      doesn't mean we should abandon randomised controlled trials.

PMID- 25858124
TI  - Corrigendum: Expression of cytokines, growth factors and apoptosis-related signal
      molecules in chronic pressure ulcer wounds healing.

PMID- 25858125
TI  - Mammography screening causes anxiety in women.

PMID- 25858126
TI  - The use of benzodiazepines for tinnitus: systematic review.
AB  - OBJECTIVES: To investigate the effectiveness of benzodiazepine use for subjective
      tinnitus and to consider this in the context of the concomitant side effects.
      METHODS: A systematic search of several databases using the terms 'tinnitus' and
      'benzodiazepines' was conducted to find clinical trials of benzodiazepines and
      comparators in tinnitus patients. These studies were then assessed for risk of
      bias. RESULTS: Six clinical trials were included. Clonazepam was found to be
      effective in three studies, but these studies had limitations regarding adequate
      blinding. The effectiveness of alprazolam was equivocal. Diazepam was not
      effective in two studies and oxazepam was effective in one study. CONCLUSION:
      Benzodiazepine use for subjective tinnitus does not have a robust evidence base.
      Clonazepam has the most evidence to support its use and is relatively less likely
      to lead to abuse because of its longer half-life, but caution is still needed
      given the other serious side effects.

PMID- 25858127
TI  - [Chronic B-cell lymphoproliferative disorders with hairy cells].
AB  - The standardized blood smear examination is the first step in the diagnosis of a
      B-cell chronic lymphoproliferative disorder and can guide further investigations.
      In the laboratory, the identification of hairy cells on blood smear is a matter
      of daily practice. Hairy cell proliferations represent heterogeneous entities and
      their respective diagnoses can be difficult. If hairy cell leukemia (HCL) and
      splenic marginal zone lymphoma (SMZL) represent separate entities, the variant
      form of HCL (HCLv) and splenic diffuse red pulp small B-cell lymphoma (SDRPL)
      remain provisional entities in the 2008 WHO classification. We discuss the main
      clinical and biological characteristics of these four entities and appropriate
      means to characterize, identify and distinguish from each other; standardized
      blood smear examination, multiparameter flow cytometry analysis, analysis of the
      repertoire of immunoglobulins heavy chains genes and their mutational status
      (mutated or unmutated profile), molecular analyses: BRAF gene V600E mutation in
      HCL and MAP2K1 gene mutations in HCLv. We also discuss the main therapeutic
      aspects with emphasis on the new targeted drugs that enter into force in the
      therapeutic arsenal. 

PMID- 25858128
TI  - PcG and trxG in plants - friends or foes.
AB  - The highly-conserved Polycomb group (PcG) and trithorax group (trxG) proteins
      play major roles in regulating gene expression and maintaining developmental
      states in many organisms. However, neither the recruitment of Polycomb repressive
      complexes (PRC) nor the mechanisms of PcG and trxG-mediated gene silencing and
      activation are well understood. Recent progress in Arabidopsis research
      challenges the dominant model of PRC2-dependent recruitment of PRC1 to target
      genes. Moreover, evidence indicates that diverse forms of PRC1, with shared
      components, are a common theme in plants and mammals. Although trxG is known to
      antagonize PcG, emerging data reveal that trxG can also repress gene expression,
      acting cooperatively with PcG. We discuss these recent findings and highlight the
      employment of diverse epigenetic mechanisms during development in plants and
      animals. 

PMID- 25858129
TI  - Biomimetic synthetic self-assembled hydrogels for cell transplantation.
AB  - The development of three-dimensional matrices capable of recapitulating the main
      features of native extracellular matrix and contribute for the establishment of a
      favorable microenvironment for cell behavior and fate is expected to circumvent
      some of the main limitations of cell-based therapies. In this context, self
      assembly has emerged as a promising strategy to engineer cell-compatible
      hydrogels. A wide number of synthetically-derived biopolymers, such as proteins,
      peptides and DNA/RNA, with intrinsic ability to self-assemble into well-defined
      nanofibrous structures, are being explored. The resulting hydrogels, in addition
      to closely resembling the architecture of native cellular microenvironments,
      present a versatile and dynamic behavior that allows them to be designed to
      undergo sol-to-gel transition in response to exogenous stimulus. This review
      presents an overview on the state-of-the-art of the different strategies being
      explored for the development of injectable synthetic self-assembled hydrogels for
      cell transplantation and/or recruitment of endogenous cells, with an emphasis on
      their biological performance, both in vitro and in vivo. Systems based on
      peptides are the most widely explored and have already generated promising
      results in pre-clinical in vivo studies involving different repair/regenerative
      scenarios, including cartilage, bone, nerve and heart. On the other hand, systems
      based on DNA and hybrid hydrogels are now emerging for application in the
      biomedical field with high potential. Finally, the main challenges hampering the
      translation of these systems to the clinic and the issues that need to be
      addressed for these to progress from bench-to-bedside are discussed. 

PMID- 25858130
TI  - Chlorotoxin-conjugated nanoparticles for targeted imaging and therapy of glioma.
AB  - This review reports the recent advances in chlorotoxin (CTX)-targeted
      nanoparticles (NPs) for imaging and therapy of glioma. CTX has been identified as
      a targeting ligand to specifically bind to glioma. Through different conjugation
      approaches, CTX can be conjugated onto iron oxide NPs, quantum dots, and rare
      earth upconversion NPs for targeted magnetic resonance and fluorescence imaging
      of glioma. Likewise, CTX-conjugated NPs can also be used as a carrier system to
      load anticancer drugs or therapeutic genes for targeted chemotherapy or gene
      therapy of glioma, respectively. Some of the key developments in this area of
      research will be introduced in detail. Challenges and future perspectives in the
      development of CTX-conjugated NPs will be discussed. 

PMID- 25858131
TI  - Gelatin-ionic liquid based platform for glucose detection.
AB  - Herein, we have fabricated a novel platform consisting of gelatin B in ionic
      liquid [1-ethyl- 3-methylimidazolium chloride [C2mim][Cl] (ionic liquid, IL)]
      formed ionogels (Ig) by dissolution method and used it for glucose detection. The
      ionogels were deposited onto indium tin oxide (ITO) coated glass plate using drop
      casting technique. Glucose oxidase (GOx) was selected as a model enzyme to
      investigate its interaction with Ig/ITO electrode using electrochemical and
      optical methods. Structural and morphological studies of the Ig/ITO electrode
      were characterized by scanning electron microscopy, Fourier transform infrared
      spectroscopy and cyclic voltmmetry before and after GOx immobilization. It was
      found that [C2mim][Cl] enhanced electrocatalytic behaviour of the fabricated
      electrode which provided electron transfer rate constant as Ks ~ 0.113 s(-1).
      Response study of GOx/Ig/ITO bioelectrode as a function of glucose concentration
      was monitored. These gelatin-ionic liquid based bioelectrodes showed following
      results obtained from electrochemical technique linearity ~ 1-20 mM, and low
      value of Michaelis-Menten constant, Km ~ 0.174 mM with sensitivity ~ 4.6uA mM(-1)
      cm(-2). In contrast, the optical detection of glucose exhibited linearity in the
      range of 6-20 mM, value of Km ~ 3.8 mM with sensitivity 6.76 x 10(-3) Abs/mM
      cm(2). This clearly indicated that the prepared ionogel based electrodes will
      provide a promising platform for glucose detection. 

PMID- 25858132
TI  - Cationic polymers and their self-assembly for antibacterial applications.
AB  - The present article focuses on the amphiphilic cationic polymers as antibacterial
      agents. These polymers undergo self-assembly in aqueous conditions and impart
      biological activity by efficiently interacting with the bacterial cell wall,
      hence, used in preparing chemical disinfectants and biocides. Both cationic
      charge as well as hydrophobic segments facilitate interactions with the bacterial
      cell surface and initiate its disruption. The perturbation in transmembrane
      potential causes leakage of cytosolic contents followed by cell death. Out of two
      categories of macromolecules, peptide oligomers and cationic polymers, which have
      extensively been used as antibacterials, we have elaborated on the current
      advances made in the area of cationic polymer-based (naturally occurring and
      commonly employed synthetic polymers and their modified analogs) antibacterial
      agents. The development of polymer-based antibacterials has helped in addressing
      challenges posed by the drug-resistant bacterial infections. These polymers
      provide a new platform to combat such infections in the most efficient manner.
      This review presents concise discussion on the amphiphilic cationic polymers and
      their modified analogs having low hemolytic activity and excellent antibacterial
      activity against array of fungi, bacteria and other microorganisms. 

PMID- 25858133
TI  - Interlocked systems in nanomedicine.
AB  - The concept of Nanomedicine emerged along with the new millennium, and it is
      expected to provide solutions to some of modern medicine's unsolved problems.
      Nanomedicine offers new hopes in several critical areas such as cancer treatment,
      viral and bacterial infections, medical imaging, tissue regeneration, and
      theranostics. To explore all these applications, a wide variety of nanomaterials
      have been developed which include liposomes, dendrimers, nanohydrogels and
      polymeric, metallic and inorganic nanoparticles. Recently, interlocked systems,
      namely rotaxanes and catenanes, have been incorporated into some of these
      chemical platforms in an attempt to improve their performance. This review focus
      on the nanomedicine applications of nanomaterials containing interlocked
      structures. The introduction gives an overview on the significance of
      interdisciplinary science in the progress of the nanomedicine field, and it
      explains the evolution of interlocked molecules until their application in
      nanomedicine. The following sections are organized by the type of interlocked
      structure, and it comprises details of the in vitro and/or in vivo experiments
      involving each material: rotaxanes as imaging agents, rotaxanes as cytotoxic
      agents, rotaxanes as peptide transporters, mechanized silica nanoparticles as
      stimuli responsive drug delivery systems, and polyrotaxanes as drug and gene
      delivery systems. 

PMID- 25858134
TI  - Recent advances in self-assembled fluorescent DNA structures and probes.
AB  - The combined efforts of chemistry, nanotechnology, and spectroscopy led to the
      development of self-assembled fluorescent DNA nanostructures, an inexhaustible
      source of refined and bizarre tools and powerful techniques for research and
      diagnostic applications. This multidisciplinary area has tremendous prospects for
      science and technology. 

PMID- 25858135
TI  - Vitamin E-TPGS stabilized self-assembled tripeptide nanostructures for drug
      delivery.
AB  - Self-assembled peptides and specifically small peptide based nanostructures have
      been the focus of research in past decade due to their potential biological
      applications. In this study, we prepared a protected peptide, Boc-Pro-Phe-Gly
      OMe, which self-assembled in aqueous solutions leading to the formation of
      nanostructures and ability to act as a drug carrier. Dynamic light scattering
      (DLS) measurements showed nanostructures with average size of 119.6 nm containing
      hydrophobic core, wherein hydrophobic drugs, viz, eosin, aspirin and curcumin,
      were successfully encapsulated. These encapsulated nanostructures, were further
      stabilized with Vitamin E-TPGS. In-vitro drug release studies revealed the
      release of drugs in controlled fashion from the nanostructures. The results
      advocate the potential of the proposed peptide nanostructures as controlled drug
      delivery systems and could be used in other biomedical applications. 

PMID- 25858136
TI  - Acute visual loss following dapsone-induced methemoglobinemia and hemolysis.
AB  - OBJECTIVE: While methemoglobinemia is a possible complication of chronic dapsone
      therapy or of acute overdose, serious adverse manifestations related to
      methemoglobin formation remain rare. We present an unusual case with severe
      ischemic retinal injury. CASE REPORT: A 30-year-old African woman presented with
      a sudden decrease of visual acuity secondary to retinal ischemia. She was
      chronically treated with dapsone (50 mg/day) for a dermatologic disease and
      denied any drug overdose. However, the determination of serum dapsone level on
      admission revealed a largely supratherapeutic concentration (20,044 MUg/ml
      compared with 1-3.5 +/- 0.5 MUg/ml for therapeutic levels). The methemoglobin
      level at admission was 32% (sulfhemoglobin 1.2%), with hemoglobin level, 7.4
      g/dl, schistocytes count, 2-5%, lactate dehydrogenase level, 580 IU/l, and
      haptoglobin level, < 10 mg/dl. The patient had both alpha-thalassemia and sickle
      cell trait. She was treated with methylene blue, vitamin C, and exchange
      transfusion. There was no improvement in visual symptoms over time. CONCLUSIONS:
      In a patient with supratherapeutic serum levels of dapsone, the severity of
      visual injury was associated with dapsone-induced methemoglobinemia and
      hemolysis, and perhaps also with some hematologic predisposing factors.

PMID- 25858138
TI  - Massive cerebral air embolism after blunt chest trauma with full neurological
      recovery.
AB  - Cerebral air embolism (CAE) is a common, often lethal, complication in blunt and
      penetrating chest trauma. The factors affecting the outcome of CAE patients are
      poorly understood, and there is no generally accepted treatment algorithm. In
      this report, we present the case of a 28-year-old male motorcyclist with a
      massive CAE, including bilateral internal carotid artery air on computed
      tomographic examination following blunt chest trauma. With prehospital
      intubation, oxygen, transfusion, and open laparotomy but without any specific
      treatment regarding the CAE, a follow-up computed tomography (CT) scan
      approximately 6 hours later showed resolution of the cerebrovascular air.
      Recovery was unremarkable, and the patient was discharged neurologically intact
      after 22 days. 

PMID- 25858137
TI  - Fab fragments of ovine antibody to colchicine enhance its clearance in the rat.
AB  - CONTEXT: Colchicine is an anti-inflammatory alkaloid used for the treatment of
      acute gout, but has a narrow therapeutic index. Colchicine overdoses are
      relatively rare, but have high mortality requiring rapid treatment. OBJECTIVE: To
      evaluate the ability of a newly available ovine fragment antigen-binding (Fab)
      antibody to colchicine (ColchiFab(TM)) to protect rats against renal and other
      injury 24 h after colchicine ingestion. MATERIALS AND METHODS: Rats were gavaged
      with colchicine (5 mg/kg), then 2 h later injected intraperitoneally with 5 ml of
      sterile saline, or Fab anti-colchicine, a newly available ovine antibody to
      colchicine. Samples of blood were taken at 1, 2, 5 and 24 h after gavage, and
      urine was collected from 5 to 24 h after gavage. Concentrations of colchicine in
      tissue, blood and urine were measured by liquid chromatography/mass spectrometry,
      concentrations of Fab anti-colchicine, urinary neutrophil gelatinase-associated
      lipocalin (NGAL) and kidney injury molecule-1 or KIM-1 by enzyme-linked
      immunosorbent assay or ELISA, while concentrations of creatine kinase and
      creatinine (Cr) were measured enzymatically. RESULTS: Colchicine equilibrated
      rapidly throughout the body and increased serum creatine kinase. Fab anti
      colchicine also rapidly redistributed to the blood and remained at high
      concentrations over 24 h. Fab anti-colchicine caused a rapid 7.1-fold increase in
      serum colchicine level, followed by excretion of both colchicine and Fab anti
      colchicine through the urine. This was associated with the accumulation of
      colchicine in the kidney, a reversal of colchicine-induced diarrhoea, and
      increasing urinary NGAL level; from 168 +/- 48 to 477 +/- 255 ng/mmol Cr [mean +/
      standard deviation or SD]. DISCUSSION: Fab anti-colchicine greatly increased the
      clearance of colchicine, although increasing NGAL level suggested the presence of
      mild kidney damage. CONCLUSION: These data suggest clinical utility for Fab anti
      colchicine in the treatment of colchicine overdose.

PMID- 25858139
TI  - Role of fumonisin B1 on DNA methylation changes in rat kidney and liver cells.
AB  - CONTEXT: Fumonisin B1 (FB1) is a mycotoxin produced by Fusarium verticillioides
      (Sacc.) Nirenberg (Nectriaceae) mold that contaminates maize and other
      agricultural products. Although the effects of FB1 on sphingolipid metabolism are
      clear, little is known about early molecular changes associated with FB1
      carcinogenicity. OBJECTIVE: Alteration on DNA methylation, as an early event in
      non-genotoxic carcinogenesis, may play an important role in the mechanism of FB1
      toxiciy. MATERIALS AND METHODS: Dose-related effects of FB1 (1-50 uM for 24 h) on
      global DNA methylation by using high-performance liquid chromatography with UV
      diode array detection (HPLC-UV/DAD) and CpG promoter methylation by methylation
      specific PCR (MSP) were performed in rat liver (Clone 9) and rat kidney (NRK-52E)
      epithelial cells. RESULTS: Cell viability reduction is 39% and 34% by the XTT
      test and LDH release in the growth medium is 32% and 26% at 200 uM of FB1
      treatment in Clone 9 and NRK-52E cells, respectively. No significant dose-related
      effects of FB1 on global DNA methylation which ranged from 4 to 5% were observed
      in both cells compared with controls. Promoter regions of c-myc gene were
      methylated (>33%) at 10 and 50 uM of FB1 treatment in Clone 9 cells while it was
      unmethylated in NRK-52E cells. Promoter regions of p15 gene were unmethylated
      while VHL gene were found to be methylated (>33%) at 10, 25, and 50 uM and 10 and
      50 uM of FB1 treatment in Clone 9 and NRK-52E cells, respectively. DISCUSSION AND
      CONCLUSION: Alteration in DNA methylation might play an important role in the
      toxicity of FB1 in risk assessment process.

PMID- 25858141
TI  - Plants, viruses and the environment: Ecology and mutualism.
AB  - Since the discovery of Tobacco mosaic virus nearly 120 years ago, most studies on
      viruses have focused on their roles as pathogens. Virus ecology takes a different
      look at viruses, from the standpoint of how they affect their hosts' interactions
      with the environment. Using the framework of symbiotic relationships helps put
      the true nature of viruses into perspective. Plants clearly have a long history
      of relationships with viruses that have shaped their evolution. In wild plants
      viruses are common but usually asymptomatic. In experimental studies plant
      viruses are sometimes mutualists rather than pathogens. Virus ecology is closely
      tied to the ecology of their vectors, and the behavior of insects, critical for
      transmission of many plant viruses, is impacted by virus-plant interactions.
      Virulence is probable not beneficial for most host-virus interactions, hence
      commensal and mutualistic relationships are almost certainly common, in spite of
      the paucity of literature on beneficial viruses. 

PMID- 25858140
TI  - Viruses and the autophagy pathway.
AB  - Studies of the cellular autophagy pathway have exploded over the past twenty
      years. Now appreciated as a constitutive degradative mechanism that promotes
      cellular homeostasis, autophagy is also required for a variety of developmental
      processes, cellular stress responses, and immune pathways. Autophagy certainly
      acts as both an anti-viral and pro-viral pathway, and the roles of autophagy
      depend on the virus, the cell type, and the cellular environment. The goal of
      this review is to summarize, in brief, what we know so far about the relationship
      between autophagy and viruses, particularly for those who are not familiar with
      the field. With a massive amount of relevant published data, it is simply not
      possible to be comprehensive, or to provide a complete "parade of viruses", and
      apologies are offered to researchers whose work is not described herein. Rather,
      this review is organized around general themes regarding the relationship between
      autophagy and animal viruses. 

PMID- 25858142
TI  - Light-induced plasticity in leaf hydraulics, venation, anatomy, and gas exchange
      in ecologically diverse Hawaiian lobeliads.
AB  - Leaf hydraulic conductance (Kleaf ) quantifies the capacity of a leaf to
      transport liquid water and is a major constraint on light-saturated stomatal
      conductance (gs ) and photosynthetic rate (Amax ). Few studies have tested the
      plasticity of Kleaf and anatomy across growth light environments. These provided
      conflicting results. The Hawaiian lobeliads are an excellent system to examine
      plasticity, given the striking diversity in the light regimes they occupy, and
      their correspondingly wide range of Amax , allowing maximal carbon gain for
      success in given environments. We measured Kleaf , Amax , gs and leaf anatomical
      and structural traits, focusing on six species of lobeliads grown in a common
      garden under two irradiances (300/800 MUmol photons m(-2)  s(-1) ). We tested
      hypotheses for light-induced plasticity in each trait based on expectations from
      optimality. Kleaf , Amax , and gs differed strongly among species. Sun/shade
      plasticity was observed in Kleaf , Amax, and numerous traits relating to lamina
      and xylem anatomy, venation, and composition, but gs was not plastic with growth
      irradiance. Species native to higher irradiance showed greater hydraulic
      plasticity. Our results demonstrate that a wide set of leaf hydraulic, stomatal,
      photosynthetic, anatomical, and structural traits tend to shift together during
      plasticity and adaptation to diverse light regimes, optimizing performance from
      low to high irradiance. 

PMID- 25858144
TI  - miR-25 Modulates Invasiveness and Dissemination of Human Prostate Cancer Cells
      via Regulation of alphav- and alpha6-Integrin Expression.
AB  - Altered microRNA (miRNA; miR) expression is associated with tumor formation and
      progression of various solid cancers. A major challenge in miRNA expression
      profiling of bulk tumors is represented by the heterogeneity of the
      subpopulations of cells that constitute the organ, as well as the tumor tissue.
      Here, we analyzed the expression of miRNAs in a subpopulation of epithelial
      stem/progenitor-like cells in human prostate cancer [prostate cancer stem cell
      (PCSC)] and compared their expression profile to more differentiated cancer
      cells. In both cell lines and clinical prostate cancer specimens, we identified
      that miR-25 expression in PCSCs was low/absent and steadily increased during
      their differentiation into cells with a luminal epithelial phenotype. Functional
      studies revealed that overexpression of miR-25 in prostate cancer cell lines and
      selected subpopulation of highly metastatic and tumorigenic cells (ALDH(high))
      strongly affected the invasive cytoskeleton, causing reduced migration in vitro
      and metastasis via attenuation of extravasation in vivo. Here, we show, for the
      first time, that miR-25 can act as a tumor suppressor in highly metastatic PCSCs
      by direct functional interaction with the 3'-untranslated regions of proinvasive
      alphav- and alpha6-integrins. Taken together, our observations suggest that miR
      25 is a key regulator of invasiveness in human prostate cancer through its direct
      interactions with alphav- and alpha6-integrin expression.

PMID- 25858143
TI  - SOCS2 Controls Proliferation and Stemness of Hematopoietic Cells under Stress
      Conditions and Its Deregulation Marks Unfavorable Acute Leukemias.
AB  - Hematopoietic stem cells (HSC) promptly adapt hematopoiesis to stress conditions,
      such as infection and cancer, replenishing bone marrow-derived circulating
      populations, while preserving the stem cell reservoir. SOCS2, a feedback
      inhibitor of JAK-STAT pathways, is expressed in most primitive HSC and is
      upregulated in response to STAT5-inducing cytokines. We demonstrate that Socs2
      deficiency unleashes HSC proliferation in vitro, sustaining STAT5 phosphorylation
      in response to IL3, thrombopoietin, and GM-CSF. In vivo, SOCS2 deficiency leads
      to unrestricted myelopoietic response to 5-fluorouracil (5-FU) and, in turn,
      induces exhaustion of long-term HSC function along serial bone marrow
      transplantations. The emerging role of SOCS2 in HSC under stress conditions
      prompted the investigation of malignant hematopoiesis. High levels of SOCS2
      characterize unfavorable subsets of acute myeloid and lymphoblastic leukemias,
      such as those with MLL and BCR/ABL abnormalities, and correlate with the
      enrichment of genes belonging to hematopoietic and leukemic stemness signatures.
      In this setting, SOCS2 and its correlated genes are part of regulatory networks
      fronted by IKZF1/Ikaros and MEF2C, two transcriptional regulators involved in
      normal and leukemic hematopoiesis that have never been linked to SOCS2.
      Accordingly, a comparison of murine wt and Socs2(-/-) HSC gene expression in
      response to 5-FU revealed a significant overlap with the molecular programs that
      correlate with SOCS2 expression in leukemias, particularly with the oncogenic
      pathways and with the IKZF1/Ikaros and MEF2C-predicted targets. Lentiviral gene
      transduction of murine hematopoietic precursors with Mef2c, but not with Ikzf1,
      induces Socs2 upregulation, unveiling a direct control exerted by Mef2c over
      Socs2 expression.

PMID- 25858145
TI  - Silencing beta3 Integrin by Targeted ECO/siRNA Nanoparticles Inhibits EMT and
      Metastasis of Triple-Negative Breast Cancer.
AB  - Metastatic breast cancer is the second leading cause of cancer-related deaths
      among women. Triple-negative breast cancer (TNBC) is a highly aggressive
      subcategory of breast cancer and currently lacks well-defined molecular targets
      for effective targeted therapies. Disease relapse, metastasis, and drug
      resistance render standard chemotherapy ineffective in the treatment of TNBC.
      Because previous studies coupled beta3 integrin (ITGB3) to epithelial-mesenchymal
      transition (EMT) and metastasis, we exploited beta3 integrin as a therapeutic
      target to treat TNBC by delivering beta3 integrin siRNA via lipid ECO-based
      nanoparticles (ECO/sibeta3). Treatment of TNBC cells with ECO/sibeta3 was
      sufficient to effectively silence beta3 integrin expression, attenuate TGFbeta
      mediated EMT and invasion, restore TGFbeta-mediated cytostasis, and inhibit three
      dimensional organoid growth. Modification of ECO/sibeta3 nanoparticles with an
      RGD peptide via a PEG spacer enhanced siRNA uptake by post-EMT cells. Intravenous
      injections of RGD-targeted ECO/sibeta3 nanoparticles in vivo alleviated primary
      tumor burden and, more importantly, significantly inhibited metastasis. In the
      span of 16 weeks of the experiments and observations, including primary tumor
      resection at week 9 and release from the treatment for 4 weeks, the mice bearing
      orthotopic, TGFbeta-prestimulated MDA-MB-231 tumors that were treated with RGD
      targeted ECO/sibeta3 nanoparticles were free of metastases and relapse, in
      comparison with untreated mice. Collectively, these results highlight ECO/sibeta3
      nanoparticles as a promising therapeutic regimen to combat TNBC.

PMID- 25858146
TI  - Hepcidin regulation in prostate and its disruption in prostate cancer.
AB  - Hepcidin is a circulating peptide hormone made by the liver that is a central
      regulator of systemic iron uptake and recycling. Here, we report that prostate
      epithelial cells also synthesize hepcidin, and that synthesis and secretion of
      hepcidin are markedly increased in prostate cancer cells and tissue. Prostatic
      hepcidin functions as an autocrine hormone, decreasing cell surface ferroportin,
      an iron exporter, increasing intracellular iron retention, and promoting prostate
      cancer cell survival. Synthesis of hepcidin in prostate cancer is controlled by a
      unique intersection of pathways that involves BMP4/7, IL6, Wnt, and the dual BMP
      and Wnt antagonist, SOSTDC1. Epigenetic silencing of SOSTDC1 through methylation
      is increased in prostate cancer and is associated with accelerated disease
      progression in patients with prostate cancer. These results establish a new
      connection between iron metabolism and prostate cancer, and suggest that
      prostatic dysregulation of hepcidin contributes to prostate cancer growth and
      progression.

PMID- 25858147
TI  - Lin28B/Let-7 Regulates Expression of Oct4 and Sox2 and Reprograms Oral Squamous
      Cell Carcinoma Cells to a Stem-like State.
AB  - Lin28, a key factor for cellular reprogramming and generation of induced
      pluripotent stem cell (iPSC), makes a critical contribution to tumorigenicity by
      suppressing Let-7. However, it is unclear whether Lin28 is involved in regulating
      cancer stem-like cells (CSC), including in oral squamous carcinoma cells (OSCC).
      In this study, we demonstrate a correlation between high levels of Lin28B, Oct4,
      and Sox2, and a high percentage of CD44(+)ALDH1(+) CSC in OSCC. Ectopic Lin28B
      expression in CD44(-)ALDH1(-)/OSCC cells was sufficient to enhance Oct4/Sox2
      expression and CSC properties, whereas Let7 co-overexpression effectively
      reversed these phenomena. We identified ARID3B and HMGA2 as downstream effectors
      of Lin28B/Let7 signaling in regulating endogenous Oct4 and Sox2 expression. Let7
      targeted the 3' untranslated region of ARID3B and HMGA2 and suppressed their
      expression, whereas ARID3B and HMGA2 increased the transcription of Oct4 and
      Sox2, respectively, through promoter binding. Chromatin immunoprecipitation
      assays revealed a direct association between ARID3B and a specific ARID3B-binding
      sequence in the Oct4 promoter. Notably, by modulating Oct4/Sox2 expression, the
      Lin28B-Let7 pathway not only regulated stemness properties in OSCC but also
      determined the efficiency by which normal human oral keratinocytes could be
      reprogrammed to iPSC. Clinically, a Lin28B(high)-Let7(low) expression pattern was
      highly correlated with high levels of ARID3B, HMGA2, OCT4, and SOX2 expression in
      OSCC specimens. Taken together, our results show how Lin28B/Let7 regulates key
      cancer stem-like properties in oral squamous cancers.

PMID- 25858148
TI  - TGFbeta Is a Master Regulator of Radiation Therapy-Induced Antitumor Immunity.
AB  - T cells directed to endogenous tumor antigens are powerful mediators of tumor
      regression. Recent immunotherapy advances have identified effective interventions
      to unleash tumor-specific T-cell activity in patients who naturally develop them.
      Eliciting T-cell responses to a patient's individual tumor remains a major
      challenge. Radiation therapy can induce immune responses to model antigens
      expressed by tumors, but it remains unclear whether it can effectively prime T
      cells specific for endogenous antigens expressed by poorly immunogenic tumors. We
      hypothesized that TGFbeta activity is a major obstacle hindering the ability of
      radiation to generate an in situ tumor vaccine. Here, we show that antibody
      mediated TGFbeta neutralization during radiation therapy effectively generates
      CD8(+) T-cell responses to multiple endogenous tumor antigens in poorly
      immunogenic mouse carcinomas. Generated T cells were effective at causing
      regression of irradiated tumors and nonirradiated lung metastases or synchronous
      tumors (abscopal effect). Gene signatures associated with IFNgamma and immune
      mediated rejection were detected in tumors treated with radiation therapy and
      TGFbeta blockade in combination but not as single agents. Upregulation of
      programmed death (PD) ligand-1 and -2 in neoplastic and myeloid cells and PD-1 on
      intratumoral T cells limited tumor rejection, resulting in rapid recurrence.
      Addition of anti-PD-1 antibodies extended survival achieved with radiation and
      TGFbeta blockade. Thus, TGFbeta is a fundamental regulator of radiation therapy's
      ability to generate an in situ tumor vaccine. The combination of local radiation
      therapy with TGFbeta neutralization offers a novel individualized strategy for
      vaccinating patients against their tumors.

PMID- 25858149
TI  - Forecasting fish biomasses, densities, productions, and bioaccumulation
      potentials of mid-atlantic wadeable streams.
AB  - Regional fishery conditions of Mid-Atlantic wadeable streams in the eastern
      United States are estimated using the Bioaccumulation and Aquatic System
      Simulator (BASS) bioaccumulation and fish community model and data collected by
      the US Environmental Protection Agency's Environmental Monitoring and Assessment
      Program (EMAP). Average annual biomasses and population densities and annual
      productions are estimated for 352 randomly selected streams. Realized
      bioaccumulation factors (BAF) and biomagnification factors (BMF), which are
      dependent on these forecasted biomasses, population densities, and productions,
      are also estimated by assuming constant water exposures to methylmercury and
      tetra-, penta-, hexa-, and hepta-chlorinated biphenyls. Using observed biomasses,
      observed densities, and estimated annual productions of total fish from 3 regions
      assumed to support healthy fisheries as benchmarks (eastern Tennessee and
      Catskill Mountain trout streams and Ozark Mountains smallmouth bass streams), 58%
      of the region's wadeable streams are estimated to be in marginal or poor
      condition (i.e., not healthy). Using simulated BAFs and EMAP Hg fish
      concentrations, we also estimate that approximately 24% of the game fish and
      subsistence fishing species that are found in streams having detectable Hg
      concentrations would exceed an acceptable human consumption criterion of 0.185
      MUg/g wet wt. Importantly, such streams have been estimated to represent 78.2% to
      84.4% of the Mid-Atlantic's wadeable stream lengths. Our results demonstrate how
      a dynamic simulation model can support regional assessment and trends analysis
      for fisheries.

PMID- 25858150
TI  - Decreased DNA Disruption in the Porcine Neocortex with Erythromycin
      Preconditioning during Prolonged Hypothermic Circulatory Arrest: Evidence for
      Neuroprotection.
AB  - BACKGROUND AND AIM OF THE STUDY: We have previously reported that the neocortex
      is selectively vulnerable to injury in an acute porcine model of hypothermic
      circulatory arrest (HCA) at 18 degrees C. In view of recent evidence showing that
      pharmacologic preconditioning with a single dose of erythromycin induces
      tolerance against transient global cerebral ischemia in rats, we hypothesized
      that erythromycin would reduce the number of apoptotic neurons in the neocortex
      in an acute porcine model of HCA at 18 degrees C. METHODS: Fourteen piglets
      underwent 75 min of HCA at 18 degrees C following pretreatment with erythromycin
      (25 mg/kg, IV) (n = 8) or vehicle (Normal Saline 0.9%) (n = 6), applied 12 hr
      before arrest. Three served as normal controls. After gradual rewarming to a
      temperature of 36 degrees C, treatment animals were sacrificed and brains were
      perfusion-fixed and cryopreserved. Neuronal apoptosis after HCA was observed
      morphologically with hematoxylin and eosin staining, and characterized by in situ
      DNA fragmentation using terminal deoxynucleotidyl-transferase-mediated biotin
      dUTP nick end-labeling (TUNEL) histochemistry. RESULTS: Pre-ischemic conditioning
      with a single dose of the antibiotic erythromycin reduced neuronal apoptosis in
      the neocortex of the porcine brain. TUNEL-positive cells indicating DNA
      fragmentation and neuronal injury were significantly greater in the neocortex of
      animals treated with 18 degrees C HCA (2.55 +/- 1.17) compared to animals
      undergoing HCA after erythromycin preconditioning (1.76 +/- 0.91) (p <= 0.001).
      CONCLUSIONS: These results suggest that cerebral protection during HCA may be
      achieved with erythromycin pharmacological preconditioning in the porcine model.

PMID- 25858151
TI  - Conserved lamin A protein expression in differentiated cells in the earthworm
      Eudrilus eugeniae.
AB  - Lamin A is an intermediate filament protein found in most of the differentiated
      vertebrate cells but absent in stem cells. It shapes the skeletal frame structure
      beneath the inner nuclear membrane of the cell nucleus. As there are few studies
      of the expression of lamin A in invertebrates, in the present work, we have
      analyzed the sequence, immunochemical conservation and expression pattern of
      lamin A protein in the earthworm Eudrilus eugeniae, a model organism for tissue
      regeneration. The expression of lamin A has been confirmed in E. eugeniae by
      immunoblot. Its localization in the nuclear membrane has been observed by
      immunohistochemistry using two different rabbit anti-sera raised against human
      lamin A peptides, which are located at the C-terminus of the lamin A protein.
      These two antibodies detected 70 kDa lamin A protein in mice and a single 65 kDa
      protein in the earthworm. The Oct-4 positive undifferentiated blastemal tissues
      of regenerating earthworm do not express lamin A, while the Oct-4 negative
      differentiated cells express lamin A. This pattern was also confirmed in the
      earthworm prostate gland. The present study is the first evidence for the
      immunochemical identification of lamin A and Oct-4 in the earthworm. Along with
      the partial sequence obtained from the earthworm genome, the present results
      suggest that lamin A protein and its expression pattern is conserved from the
      earthworm to humans. 

PMID- 25858152
TI  - Improved n-butanol tolerance in Escherichia coli by controlling membrane related
      functions.
AB  - As the increasing demand from both chemical and fuel markets, the interest in
      producing n-butanol using biological route has been rejuvenated to engineer an
      economical fermentation process, competing with the currently-dominant chemical
      synthesis. n-Butanol has been traditionally produced from the ABE fermentation of
      Clostridium acetobutylicum. This system, however, is not economically feasible
      due to its limited efficiency and the lack of genetic modification tools for
      further improvements. Alternatively, n-butanol synthesis pathway was successfully
      transferred into Escherichia coli and rapidly improved to reach a level of
      production comparable to the native producer. Nevertheless, the toxicity of n
      butanol has become a common issue that either approach has to deal with.
      Previously, we reported our success in improving n-butanol tolerance in E. coli
      by engineering an Artificial Transcription Factor (ATF) that can modify the
      expression level of multiple targets simultaneously and improved the n-butanol
      tolerance of MG1655 strain to 1.5% (vol/vol) n-butanol. However, it was observed
      that some possible n-butanol tolerance mechanisms did not occurred upon the ATF
      expression, especially the membrane-related functions such as the homeoviscous
      adaptation, iron uptaking system, and efflux pump system. In this work, we
      attempted to enhance the n-butanol tolerance associated with the ATF by combining
      it with the membrane-related functions in E. coli, including the overexpression
      of fatty acid synthesis genes, iron-uptaking protein FeoA, and introducing a
      SrpABC efflux pump from Pseudomonas putida into E. coli. The synergistic effect
      of this combinatorial approach led to 4, 5, and 9-fold improved growths in the
      cultures containing 1, 1.5, and 2% (vol/vol) n-butanol, respectively, of an
      MG1655 knockout strain engineered for n-butanol production, and expanded the
      tolerance limit to 2% (vol/vol) n-butanol. 

PMID- 25858153
TI  - Complete genome of Jeotgalibacillus malaysiensis D5(T) consisting of a chromosome
      and a circular megaplasmid.
AB  - Jeotgalibacillus spp. are halophilic bacteria within the family Planococcaceae.
      No genomes of Jeotgalibacillus spp. have been reported to date, and their
      metabolic pathways are unknown. How the bacteria survive in hypertonic conditions
      such as seawater is yet to be discovered. As only few studies have been conducted
      on Jeotgalibacillus spp., potential applications of these bacteria are unknown.
      Here, we present the complete genome of J. malaysiensis D5(T) (=DSM 28777(T)
      =KCTC 33350(T)), which is invaluable in identifying interesting applications for
      this genus. 

PMID- 25858154
TI  - Osteogenic and osteoclastogenic differentiation of co-cultured cells in
      polylactic acid-nanohydroxyapatite fiber scaffolds.
AB  - The design of bone substitutes involves the creation of a microenvironment
      supporting molecular cross-talk between cells and scaffolds during tissue
      formation and remodelling. Bone remodelling process includes the cooperation of
      bone-building cells and bone-resorbing cells. In this paper we developed
      polylactic acid (PLA) and composite PLA-nanohydroxyapatite (nHA) scaffolds with
      20 and 50wt.% of nHA by electrospinning technique to be used in bone tissue
      engineering. The developed scaffolds have different fiber diameter, porosity with
      interconnected pores and mechanical properties. Taking cues from the bone
      environment features we investigated the differentiation of human mesenchymal
      stem cells (hMSCs) from bone marrow in osteoblasts and the osteoclastogenesis in
      the developed scaffolds in homotypic and in co-culture up to 46 days. PLA and
      composite PLA-nHA scaffolds induced osteogenic and osteoclastogenic
      differentiation. Both osteoblasts and osteoclasts displayed high expression of
      specific markers (osteopontin, osteocalcin, RANK, RANKL) and functions such as
      secretion of ALP, cathepsin K and TRAP activity on composite scaffolds especially
      on PLA-nHA containing 20wt.% of nHA. The heterotypic interactions between
      osteoblasts and osteoclasts co-cultured in the developed scaffolds triggered
      their functional differentiation and activation. 

PMID- 25858155
TI  - Drying enhances immunoactivity of spent brewer's yeast cell wall beta-D-glucans.
AB  - Due to immunological activity, microbial cell wall polysaccharides are defined as
      'biological response modifiers' (BRM). Cell walls of spent brewer's yeast also
      have some BRM activity. However, up to date there is no consensus on the use of
      spent brewer's yeast D-glucan as specific BRM in humans or animals. The aim of
      this paper is to demonstrate the potential of spent brewer's yeast beta-D-glucans
      as BRM, and drying as an efficient pretreatment to increase beta-D-glucan's
      immunogenic activity. Our results revealed that drying does not change spent
      brewer's yeast biomass carbohydrate content as well as the chemical structure of
      purified beta-D-glucan. However, drying increased purified beta-D-glucan TNF
      alpha induction activity in the murine macrophage model. We presume drying
      pretreatment enhances purity of extracted beta-D-glucan. This is corroborated
      with FT-IR analyses of the beta-D-glucan spectra. Based on our results, we
      suggest that dry spent brewer's yeast biomass can be used as a cheap source for
      high-quality beta-D-glucan extraction. Drying in combination with
      carboxylmethylation (CM), endows spent brewer's yeast beta-D-glucan with the
      immunoactivity similar or exceeding that of a well-characterized fungal BRM
      pleuran.

PMID- 25858156
TI  - Complete genome sequence of Bacillus thuringiensis tenebrionis 4AA1, a typical
      strain with toxicity to Coleopteran insects.
AB  - Bacillus thuringiensis serovar morrisoni biovar tenebrionis has been developed as
      an bioinsecticide to control Coleopteran insects in agriculture and forestry for
      a few decades. Its major crystal protein Cry3Aa was also applied to transgenic
      crops. Here we report the complete genome sequence of strain tenebrionis 4AA1,
      which has one chromosome of 5,652,292bp and six plasmids. Two crystal protein
      genes, cry3Aa and cry15Aa, locate on one single plasmid named pBMB51. This strain
      also possesses plentiful virulence factors besides crystal proteins. 

PMID- 25858158
TI  - Non-targeted lipidomics of CSF and frontal cortex grey and white matter in
      control, mild cognitive impairment, and Alzheimer's disease subjects.
AB  - OBJECTIVE: We undertook a non-targeted lipidomics analysis of post-mortem
      cerebrospinal fluid (CSF), frontal cortex grey matter, and subjacent white matter
      to define potential biomarkers that distinguish cognitively intact subjects from
      those with incipient or established dementia. Our objective was to increase our
      understanding of the role of brain lipids in pathophysiology of aging and age
      related cognitive impairment. METHODS: Levels of 650 individual lipids, across 26
      lipid subclasses, were measured utilising a high-resolution mass spectrometric
      analysis platform. RESULTS: Monoacylglycerols (MAG), diacylglycerols (DAG), and
      the very-long-chain fatty acid 26:0 were elevated in the grey matter of the mild
      cognitive impairment (MCI) and old dementia (OD) cohorts. Ethanolamine
      plasmalogens (PlsEtn) were decreased in the grey matter of the young dementia
      (YD) and OD cohorts while and phosphatidylethanolamines (PtdEth) were lower in
      the MCI, YD and OD cohorts. In the white matter, decrements in sulphatide levels
      were detected in the YD group, DAG levels were elevated in the MCI group, and MAG
      levels were increased in the YD and OD groups. CONCLUSION: The parallel changes
      in grey matter MAGs and DAGs in the MCI and OD groups suggest that these two
      cohorts may have a similar underlying pathophysiology; consistent with this, MCI
      subjects were more similar in age to OD than to YD subjects. While PlsEtn and
      phosphatidylethanolamine were decreased in the YD and OD groups they were
      unaltered in the MCI group indicating that alterations in plasmalogen synthesis
      are unlikely to represent an initiating event in the transition from MCI to
      dementia.

PMID- 25858159
TI  - Does mothers' postnatal depression influence the development of imitation?
AB  - BACKGROUND: Links between mothers' postnatal depression (PND) and children's
      cognition have been identified in several samples, but the evidence is
      inconsistent. We hypothesized that PND may specifically interfere with infants'
      imitation, an early learning ability that features in early mother-infant
      interaction and is linked to memory, causal understanding and joint attention.
      METHODS: A randomly controlled experiment on imitation was embedded into a
      longitudinal study of a representative sample of firstborn British infants, whose
      mothers were assessed for depression using the SCAN interview during pregnancy
      and at 6 months postpartum. At a mean of 12.8 months, 253 infants were presented
      with two imitation tasks that varied in difficulty, in counterbalanced order.
      RESULTS: The infants of mothers who experienced PND were significantly less
      likely than other infants in the sample to imitate the modelled actions, showing
      a 72% reduction in the likelihood of imitation. The association with PND was not
      explained by sociodemographic adversity, or a history of depression during
      pregnancy or prior to conception. Mothers' references to infants' internal states
      during mother-infant interaction at 6 months facilitated imitation at 12 months,
      but did not explain the link with PND. CONCLUSIONS: The findings support the
      hypothesis that associations between PND and later cognitive outcomes may partly
      derive from effects of the mother's illness on infants' early learning abilities.
      Support for infants' learning should be considered as an age-appropriate, child
      focused component of interventions designed to ameliorate the effects of PND.

PMID- 25858160
TI  - Organocatalyzed benzannulation for the construction of diverse anthraquinones and
      tetracenediones.
AB  - An efficient one-pot synthesis of anthraquinones and tetracenediones was achieved
      via L-proline catalyzed [4+2] cycloaddition of in situ generated azadiene from
      alpha,beta-unsaturated aldehydes and 1,4-naphthoquinones or 1,4-anthracenedione
      in good to excellent yield. This protocol constitutes an unprecedented tandem
      benzannulation that allows one-pot construction of diverse anthraquinones and
      tetracenediones in the presence of organocatalysts. This methodology was applied
      successfully to the synthesis of naturally occurring molecules and
      photochemically interesting phenanthrenequinone derivatives.

PMID- 25858161
TI  - The impact of a healthy lifestyle on Disability-Adjusted Life Years: a
      prospective cohort study.
AB  - BACKGROUND: The association between single health behaviours and incidence of and
      premature mortality from major chronic diseases, including myocardial infarction,
      stroke, diabetes mellitus, and cancer, has been demonstrated thoroughly. However,
      the association of several healthy behaviours with Disability-Adjusted Life Years
      (DALYs), which is a measure for total health combining Years Lost due to
      Disability and the Years of Life Lost due to premature mortality, has not been
      studied yet. METHODS: A prospective cohort study was conducted among 33,066
      healthy men and women aged 20 to 70 years recruited into the EPIC-NL study during
      1993 to 1997. Participants' smoking status, BMI, physical activity, and adherence
      to a Mediterranean-style diet (excluding alcohol) were investigated separately
      and combined into a simple health behaviour score ranging from 0 to 4.
      Participants were followed until the end of 2007 for occurrence of and mortality
      from the most important chronic diseases. The association between lifestyle
      (separate lifestyle factors and a simple health behaviour score) and DALYs were
      adjusted for relevant confounders. RESULTS: After a median follow-up of 12.4
      years, 6,647 disease incidences and 1,482 deaths were documented. Non-smoking,
      low BMI (BMI <25), being physically active, and adherence to a Mediterranean diet
      were all associated with a significantly lower disease burden. Persons adhering
      to all four healthy lifestyle characteristics lived a minimum of 2 years longer
      in good health (DALYs: -2.13; 95% CI: -2.65 to -1.62) than persons with none. Due
      to our non-extinct cohort, the total number of DALYs, and consequently the
      estimates, is underestimated. Therefore, true lifetime health benefits of a
      healthy lifestyle will be even larger. CONCLUSIONS: Non-smoking, a low BMI, being
      physically active, and adherence to a Mediterranean diet were associated with a
      lower disease burden. Each additional healthy lifestyle factor contributed to a
      longer life in good health.

PMID- 25858162
TI  - ED prognostication of comatose cardiac arrest patients undergoing therapeutic
      hypothermia is unreliable.
AB  - BACKGROUND: Therapeutic hypothermia (TH) improves patient survival with good
      neurologic outcome after cardiac arrest. The value of early clinician
      prognostication in the emergency department (ED) has not been studied in this
      patient population. OBJECTIVE: To determine if physicians can accurately predict
      survival and neurologic outcome at hospital discharge of resuscitated, comatose
      out-of-hospital cardiac arrest (OHCA) patients treated in a post-cardiac arrest
      clinical pathway that included TH. METHODS: This was a prospective, observational
      study conducted at a tertiary referral center. Participants were physicians
      involved in the resuscitation of OHCA patients treated with a clinical pathway
      that included TH. Immediately after patient resuscitation in the ED, physicians
      recorded their prediction of patient survival and neurologic outcome on a
      standardized questionnaire. Neurologic outcome was assessed by the cerebral
      performance category. RESULTS: Forty-two physicians completed questionnaires on
      17 patients enrolled from October 2009 to March 2010. Sensitivity and specificity
      of physician prediction of patient survival were 0.67 (95% confidence interval
      [CI], 0.45-0.83) and 0.82 (95% CI, 0.59-0.94), respectively, with an area under
      the curve of 0.74 (95% CI, 0.61-0.88), a positive likelihood ratio (+LR) of 3.72
      (95% CI, 1.30-11.02), and a -LR of 0.40 (95% CI, 0.21-0.77). Sensitivity and
      specificity of physician prediction of good neurologic outcome were 0.40 (95% CI,
      0.20-0.64) and 0.69 (95% CI, 0.50-0.84), respectively, with an area under the
      curve of 0.55 (95% CI, 0.39-0.70), a +LR of 1.29 (95% CI, 0.56-3.03), and a -LR
      of 0.87 (95% CI, 0.53-1.41). CONCLUSIONS: Physicians poorly prognosticate both
      survival and neurologic outcome in comatose OHCA patients undergoing TH.
      Premature prognostication in the ED is unreliable and should be avoided.

PMID- 25858157
TI  - Analysis of immunoglobulin transcripts and hypermutation following SHIV(AD8)
      infection and protein-plus-adjuvant immunization.
AB  - Developing predictive animal models to assess how candidate vaccines and
      infection influence the ontogenies of Envelope (Env)-specific antibodies is
      critical for the development of an HIV vaccine. Here we use two nonhuman primate
      models to compare the roles of antigen persistence, diversity and innate
      immunity. We perform longitudinal analyses of HIV Env-specific B-cell receptor
      responses to SHIV(AD8) infection and Env protein vaccination with eight different
      adjuvants. A subset of the SHIV(AD8)-infected animals with higher viral loads and
      greater Env diversity show increased neutralization associated with increasing
      somatic hypermutation (SHM) levels over time. The use of adjuvants results in
      increased ELISA titres but does not affect the mean SHM levels or CDR H3 lengths.
      Our study shows how the ontogeny of Env-specific B cells can be tracked, and
      provides insights into the requirements for developing neutralizing antibodies
      that should facilitate translation to human vaccine studies.

PMID- 25858163
TI  - Factors Influencing the Use of Psychotropic Medication for Challenging Behaviour
      in the United Kingdom: A Q Method Investigation.
AB  - OBJECTIVES: The use of pharmacological interventions to manage challenging
      behaviour displayed by adults with intellectual disabilities remains
      controversial, with current clinical guidelines in the United Kingdom advocating
      the use of less invasive psychological interventions. This exploratory study
      aimed to discover what views and beliefs are held by a sample of NHS
      professionals who provided care and treatment to adults with learning
      disabilities, about the factors that are influential in the clinical decision
      making process, surrounding the prescription of psychotropic medication, to
      manage challenging behaviour. METHODS: Q methodology was used to elucidate the
      factors considered influential in the clinical decision-making process,
      surrounding the prescription of medication to manage challenging behaviour. 55
      participants from a range of services across the north-west of England performed
      a 104 statement Q-sort task. RESULTS: Principle component factor analysis with
      varimax rotation was performed on the 55 completed Q sorts. This revealed a four
      factor solution, accounting for 44% of the variance in the data. The factors were
      interpreted and discussed under the following headings: 'High-quality safe
      ethical practice', Risk is a rationale for reactive prescribing', 'Pragmatic
      management' and 'Contextual issues'. CONCLUSIONS: The study demonstrated that Q
      methodology is a useful tool for identifying subjective viewpoints held by a
      range of professionals, with regard to the factors that influence the clinical
      decision-making process surrounding the prescription of medication. The study
      suggests that services need to identify the wider contextual factors, which are
      barriers, to the use of less invasive psychological interventions.

PMID- 25858165
TI  - Management of pregnancy in type 3 von Willebrand disease with additional platelet
      dysfunction.

PMID- 25858166
TI  - Antidepressant therapy in cancer patients: initiation and factors associated with
      treatment.
AB  - PURPOSE: We assessed the impact of a cancer diagnosis and its timing on
      antidepressant initiation. We also examined patterns of, and factors associated
      with, new antidepressant treatment in cancer patients. METHODS: We followed 61
      067 antidepressant-naive Australian Government Department of Veterans' Affairs
      clients. We used multivariable Cox proportional hazards models with time-varying
      covariates to compare antidepressant initiation in clients with and without
      cancer and to assess how initiation varies with time from diagnosis, adjusting
      for sociodemographic characteristics, health service use and co-morbidities.
      RESULTS: 17.2% (995/5795) of cancer patients initiated antidepressants and, on
      average, was more likely to initiate treatment than non-cancer controls with
      similar characteristics (initiation rate 9/100 person-years, 95% confidence
      interval: 8.5-9.6 vs 6.6/100 person-years, 95% confidence interval: 6.5-6.7). The
      peak initiation period was 12 weeks before and 16 weeks after diagnosis; cancer
      patients were 42% more likely to commence therapy than non-cancer patients
      (adjusted hazard ratio = 1.4, 1.2 to 1.7). Cancer patients with co-morbid
      disease, dispensed opioids, corticosteroids or anxiolytics and to whom death was
      approaching were more likely to initiate treatment. Median duration of
      antidepressant therapy was 16 weeks. CONCLUSION: New antidepressant treatment is
      more common in cancer populations than in cancer-free populations. Treatment was
      most commonly initiated around diagnosis time, a period when cancer drug
      treatments also commence. The timing of peak antidepressant uptake suggests
      treatment may be for short-term adjustment reactions, better managed without
      drugs. Durations of treatment are shorter than recommended for depression.

PMID- 25858164
TI  - 'Fine-tuning' blood flow to the exercising muscle with advancing age: an update.
AB  - NEW FINDINGS: What is the topic of this review? This review focuses on age
      related changes in the regulatory pathways that exist at the unique interface
      between the vascular smooth muscle and the endothelium of the skeletal muscle
      vasculature, and how these changes contribute to impairments in exercising
      skeletal muscle blood flow in the elderly. What advances does it highlight?
      Several recent in vivo human studies from our group and others are highlighted
      that have examined age-related changes in nitric oxide, endothelin-1, alpha
      adrenergic, and renin-angiotensin-aldosterone (RAAS) signaling. During dynamic
      exercise, oxygen demand from the exercising muscle is dramatically elevated,
      requiring a marked increase in skeletal muscle blood flow that is accomplished
      through a combination of systemic sympathoexcitation and local metabolic
      vasodilatation. With advancing age, the balance between these factors appears to
      be disrupted in favour of vasoconstriction, leading to an impairment in
      exercising skeletal muscle blood flow in the elderly. This 'hot topic' review
      aims to provide an update to our current knowledge of age-related changes in the
      neural and local mechanisms that contribute to this 'fine-tuning' of blood flow
      during exercise. The focus is on results from recent human studies that have
      adopted a reductionist approach to explore how age-related changes in both
      vasodilators (nitric oxide) and vasoconstrictors (endothelin-1, alpha-adrenergic
      agonists and angiotensin II) interact and how these changes impact blood flow to
      the exercising skeletal muscle with advancing age.

PMID- 25858167
TI  - Stellate Ganglion Block for Painful Congenital Venous Malformation of the Arm.
AB  - Stellate ganglion block is an established intervention used in pain management
      settings. Its use in the treatment of congenital venous malformations (VM) of the
      upper limb has never been described. We present a case of ultrasound-guided
      stellate ganglion block for a patient who derived excellent relief from pain
      uncontrolled with conservative and pharmacological methods. 

PMID- 25858168
TI  - Altered levels of endocrine biomarkers in juvenile barramundi (Lates calcarifer;
      Bloch) following exposure to commercial herbicide and surfactant formulations.
AB  - Agricultural pesticides that are known endocrine disrupting chemicals have been
      detected in waters in the Great Barrier Reef catchment and lagoon. Altered
      transcription levels of liver vitellogenin (vtg) have been documented in wild
      populations of 2 Great Barrier Reef fisheries species and were strongly
      associated with pesticide-containing runoff from sugarcane plantations. The
      present study examined endocrine and physiological biomarkers in juvenile
      barramundi (Lates calcarifer) exposed to environmentally relevant concentrations
      of commercial herbicide (ATRADEX((r)) WG Herbicide, DIUREX((r)) WG Herbicide) and
      surfactant (ACTIVATOR((r)) 90) formulations commonly used on sugarcane in the
      Great Barrier Reef catchment. Estrogenic biomarkers (namely, liver vtg messenger
      RNA and plasma 17beta-estradiol) increased following exposure to commercial
      mixtures but not to the analytical grade chemical, suggesting an estrogenic
      response to the additives. In contrast, brain aromatase (cyp19a1b) transcription
      levels, plasma testosterone and 11-ketotestosterone concentrations, and gill
      ventilation rates were not affected by any of the experimental exposures. These
      findings support the assertion that exposure to pesticide-containing runoff from
      sugarcane plantations is a potential causative agent of altered liver vtg
      transcription levels in wild barramundi. Whether exposure patterns in the Great
      Barrier Reef catchment and lagoon are sufficient to impair fish sexual and
      reproductive development and ultimately influence fish population dynamics
      remains to be determined. These findings highlight the need to consider both
      active and so-called inert ingredients in commercial pesticide formulations for
      environmental risk assessments.

PMID- 25858169
TI  - NSAIDs and spontaneous abortions - true effect or an indication bias?
AB  - AIM: The aim of the study was to characterize the extent of indication bias
      resulting from the excessive use of NSAIDs on the days preceding a spontaneous
      abortion to relieve pain. METHODS: We used data from a retrospective cohort study
      assessing the risk for spontaneous abortions following exposure to NSAIDs. Three
      definitions of exposure for cases of spontaneous abortions were compared, from
      the first day of pregnancy until the day of spontaneous abortion and until 3 and
      2 days before a spontaneous abortion. Statistical analysis was performed using
      multivariate time programmed Cox regression. RESULTS: A sharp increase was
      observed in the dispensation of indomethacin, diclofenac and naproxen, and a
      milder increase was found in the use of ibuprofen during the week before a
      spontaneous abortion. Non- selective COX inhibitors in general and specifically
      diclofenac and indomethacin were found to be associated with spontaneous
      abortions when the exposure period was defined until the day of spontaneous
      abortion (hazard ratio (HR) 1.15, 95% confidence interval (CI) 1.04, 1.28; HR
      1.31, 95% CI 1.08, 1.59 and HR 3.33, 95% CI 2.09, 5.29, respectively). The effect
      disappears by excluding exposures occurring on the day before the spontaneous
      abortion for non-selective COX inhibitors and on the last week before the
      spontaneous abortion for indomethacin. In general, decreasing HRs were found with
      the exclusion of exposures occurring on the days immediately before the
      spontaneous abortion. CONCLUSIONS: The increased use of NSAIDs during the last
      few days that preceded a spontaneous abortion to relieve pain associated with the
      miscarriage could bias studies assessing the association between exposure to
      NSAIDs and spontaneous abortions.

PMID- 25858170
TI  - Assessment of cell viability, early apoptosis, and hematopoietic potential in
      umbilical cord blood units after storage.
AB  - BACKGROUND: Successful hematopoietic stem cell transplantation using stored
      umbilical cord blood (CB) largely depends on cell dose and quality of CB units.
      The aim of this study was to assess the degree of early apoptosis, in addition to
      cell viability and hematopoietic potential, in umbilical CB units after storage.
      STUDY DESIGN AND METHODS: Sixty CB units that had been cryopreserved for up to 8
      years in a single public CB bank were investigated. After the CB units were
      thawed, cell viability and early apoptosis of total nucleated cells (TNCs),
      mononuclear cells (MNCs), and CD34+ cells were determined using flow cytometric
      method based on 7-aminoactinomycin D (7-AAD) and annexin V staining. Next,
      clonogenic assays to predict graft potency were performed. RESULTS: Postthawing
      cell viability values determined by 7-AAD were as follows: TNCs, 78.8% +/- 5.8%;
      MNCs, 88.4% +/- 5.8%; and CD34+ cells, 94.1% +/- 3.2%. Cell viability values
      using 7-AAD and annexin V dual staining were as follows: TNCs, 71.2% +/- 11.3%;
      MNCs, 83.1% +/- 7.0%; and CD34+ cells, 88.8% +/- 6.0%. Early apoptotic cells (7
      AAD-negative and annexin V-positive cells) in TNCs, MNCs, and CD34+ cells were
      6.4% +/- 3.5%, 5.4% +/- 3.1%, and 5.3% +/- 4.1%, respectively. The corrected
      colony-forming unit-granulocyte-macrophage content per 100 CD34+ cells was 67.5
      +/- 48.7. CONCLUSIONS: Postthawing cell viability determined by flow cytometric
      methods was in the following order: TNCs < MNCs < CD34+ cells. CD34+ cell
      viability was nearly identical to that of fresh CB 48 hours after collection.
      Necrosis or apoptosis in cryopreserved CB units did not accelerate during
      storage.

PMID- 25858171
TI  - Development of an Experimental Animal Model for Lower Back Pain by Percutaneous
      Injury-Induced Lumbar Facet Joint Osteoarthritis.
AB  - We report generation and characterization of pain-related behavior in a minimally
      invasive facet joint degeneration (FJD) animal model in rats. FJD was produced by
      a non-open percutaneous puncture-induced injury on the right lumbar FJs at three
      consecutive levels. Pressure hyperalgesia in the lower back was assessed by
      measuring the vocalization response to pressure from a force transducer. After
      hyperalgesia was established, pathological changes in lumbar FJs and alterations
      of intervertebral foramen size were assessed by histological and imaging
      analyses. To investigate treatment options for lumber FJ osteoarthritis-induced
      pain, animals with established hyperalgesia were administered with analgesic
      drugs, such as morphine, a selective COX-2 inhibitor, a non-steroidal anti
      inflammatory drug (NSAID) (ketorolac), or pregabalin. Effects were assessed by
      behavioral pain responses. One week after percutaneous puncture-induced injury of
      the lumbar FJs, ipsilateral primary pressure hyperalgesia developed and was
      maintained for at least 12 weeks without foraminal stenosis. Animals showed
      decreased spontaneous activity, but no secondary hyperalgesia in the hind paws.
      Histopathological and microfocus X-ray computed tomography analyses demonstrated
      that the percutaneous puncture injury resulted in osteoarthritis-like structural
      changes in the FJs cartilage and subchondral bone. Pressure hyperalgesia was
      completely reversed by morphine. The administration of celecoxib produced
      moderate pain reduction with no statistical significance while the administration
      of ketorolac and pregabalin produced no analgesic effect on FJ osteoarthritis
      induced back pain. Our animal model of non-open percutanous puncture-induced
      injury of the lumbar FJs in rats shows similar characteristics of low back pain
      produced by human facet arthropathy.

PMID- 25858173
TI  - Gold-catalysed glycosylation reaction using an easily accessible leaving group.
AB  - Gold(III)-catalysed glycosylation reaction has been developed by employing a new
      and easily accessible leaving group synthesized from ethyl cyanoacetate. Several
      nucleophiles like alcohols, thiols, allyltrimethylsilane, trimethylsilyl azide
      and triethylsilane have been reacted to make the corresponding glycosides in good
      yields and with marginal to excellent alpha-selectivity.

PMID- 25858172
TI  - Both serum 25-hydroxyvitamin D and calcium levels may increase the risk of
      incident prostate cancer in Caribbean men of African ancestry.
AB  - Circulating 25-hydroxyvitamin D [25(OH)D] concentrations have been associated
      with both higher and lower risk of prostate cancer (PCa), whereas elevated levels
      of circulating calcium has been related to higher risks. However, there are few
      studies that account for effects of both calcium and 25(OH)D concentrations on
      incident PCa in a black population. We examined these relationships in a case
      control study of men 40-80 years old with newly diagnosed, histologically
      confirmed PCa in Jamaica, a tropical country. Mean serum calcium concentrations
      was higher among cases (2.32 +/- 0.19 mmol/L) than controls, (2.27 +/- 0.30
      mmol/L) (P = 0.023) however, there were no differences in 25(OH)D by cancer
      status (cases, 33.67 +/- 12.71 ng/mL; controls (32.25 +/- 12.59 ng/mL). Serum
      calcium was not correlated with 25(OH)D (partial correlation: r, 0.06; P =
      0.287). Multivariable-adjusted models showed a positive linear relationship
      between PCa and serum calcium (OR, 1.12; CI, 1.00-1.25 per 0.1 nmol/L). Serum
      25(OH)D concentration also showed a positive association with PCa (OR, 1.23; CI,
      1.01-1.49 per 10 ng/mL). The odds of PCa in men with serum 25(OH)D tertile 2 was
      OR, 2.18; CI, 1.04-4.43 and OR, 2.47 CI, 1.20-4.90 for tertile 3 (P(trend) =
      0.013). Dietary intakes of calcium showed no relationship with PCa. Despite the
      strong relationship between serum calcium and vitamin D the mechanism by which
      each affects prostate cancer risk in men of African ancestry needs additional
      investigation.

PMID- 25858175
TI  - Oxidative Addition of Haloheteroarenes to Palladium(0): Concerted versus SN Ar
      Type Mechanism.
AB  - The kinetics of the oxidative additions of haloheteroarenes HetX (X=I, Br, Cl) to
      [Pd(0) (PPh3 )2 ] (generated from [Pd(0) (PPh3 )4 ]) have been investigated in
      THF and DMF and the rate constants have been determined. In contrast to the
      generally accepted concerted mechanism, Hammett plots obtained for substituted 2
      halopyridines and solvent effects reveal a reaction mechanism dependent on the
      halide X of HetX: an unprecedented SN Ar-type mechanism for X=Br or Cl and a
      classical concerted mechanism for X=I. These results are supported by DFT
      studies. 

PMID- 25858174
TI  - Intrinsically photosensitive retinal ganglion cell activity is associated with
      decreased sleep quality in patients with glaucoma.
AB  - PURPOSE: To use the pupillary light reflex and polysomnography to evaluate the
      function of intrinsically photosensitive retinal ganglion cells (ipRGCs) and to
      correlate this function with structural damage in glaucoma. DESIGN: Cross
      sectional study. PARTICIPANTS: A study was conducted on both eyes of 45
      participants (32 patients with glaucoma and 13 healthy subjects). METHODS: For
      the pupillary reflex evaluation, patients were tested in the dark using a
      Ganzfeld system (RETIport; Roland Consult, Brandenburg, Germany); pupil diameter
      was measured with an eye tracker system. To preferentially stimulate ipRGCs, we
      used a 1-second 470-nm flash with a luminance of 250 cd/m(2). To stimulate
      different retinal photoreceptors, we used a 1-second 640-nm flash with a
      luminance of 250 cd/m(2). All of the subjects underwent polysomnography. Subjects
      underwent standard automated perimetry and optical coherence tomography (Cirrus
      HD-OCT; Carl Zeiss Meditec Inc, Dublin, CA). MAIN OUTCOME MEASURES: Correlations
      between ipRGC activity, as measured by the pupillary light reflex, and
      polysomnography parameters, and correlations between retinal nerve fiber layer
      (RNFL) thickness and the pupillary light reflex and polysomnography parameters.
      RESULTS: The mean patient ages in the healthy and glaucoma groups were 56.8+/-7.8
      years and 61.5+/-11.6 years, respectively (P = 0.174). Patients with glaucoma had
      significantly lower average total sleep time, sleep efficiency, and minimum
      oxyhemoglobin saturation compared with the healthy subjects (P  = 0.008, P =
      0.002, and P = 0.028, respectively). Patients with glaucoma had significantly
      higher arousal durations after falling asleep and more periodic limb movements (P
      = 0.002 and P = 0.045, respectively). There was an inverse correlation between
      the rapid eye movement latency and the peak of the pupillary response to the blue
      flash (P = 0.004). The total arousals were inversely correlated with the
      sustained blue flash response (P = 0.029). The RNFL thickness was associated with
      the peak and sustained responses to the blue flash (P  <  0.001 for both
      comparisons); however, RNFL thickness was only associated with the mean oxygen
      desaturation index among the polysomnography parameters (P = 0.023). CONCLUSIONS:
      This study demonstrated that decreased ipRGC function caused by glaucoma affected
      pupillary response and sleep quality.

PMID- 25858176
TI  - Longitudinal determinants of mental health treatment-seeking by US soldiers.
AB  - BACKGROUND: Studies with members of the armed forces have found a gap between
      reports of mental health symptoms and treatment-seeking. AIMS: To assess the
      impact of attitudes on treatment-seeking behaviours in soldiers returning from a
      combat deployment. METHOD: A sample of 529 US soldiers were surveyed 4 months
      (time 1) and 12 months (time 2) post-deployment. Mental health symptoms and
      treatment-seeking attitudes were assessed at time 1; reported mental healthcare
      visits were assessed at time 2. RESULTS: Factor analysis of the total time 1
      sample revealed four attitude factors: professional concerns, practical barriers,
      preference for self-management and positive attitudes about treatment. For the
      subset of 160 soldiers reporting a mental health problem at time 1, and
      controlling for mental health symptom severity, self-management inversely
      predicted treatment-seeking; positive attitudes were positively related.
      CONCLUSIONS: Results demonstrate the importance of broadening the
      conceptualisation of barriers and facilitators of mental healthcare beyond
      stigma. Techniques and delivery models emphasising self-care may help increase
      soldiers' interest in using mental health services.

PMID- 25858177
TI  - Lung function and respiratory diseases in people with psychosis: population-based
      study.
AB  - BACKGROUND: There is little information on lung function and respiratory diseases
      in people with psychosis. AIMS: To compare the respiratory health of people with
      psychosis with that of the general population. METHOD: In a nationally
      representative sample of 8028 adult Finns, lung function was measured by
      spirometry. Information on respiratory diseases and symptoms was collected.
      Smoking was quantified with serum cotinine levels. Psychotic disorders were
      diagnosed utilising the Structured Clinical Interview for DSM-IV (SCID-I) and
      medical records. RESULTS: Participants with schizophrenia and other non-affective
      psychoses had significantly lower lung function values compared with the general
      population, and the association remained significant for schizophrenia after
      adjustment for smoking and other potential confounders. Schizophrenia was
      associated with increased odds of pneumonia (odds ratio (OR) = 4.9), chronic
      obstructive pulmonary disease (COPD, OR = 4.2) and chronic bronchitis (OR = 3.8);
      and with high cotinine levels. CONCLUSIONS: Schizophrenia is associated with
      impaired lung function and increased risk for pneumonia, COPD and chronic
      bronchitis.

PMID- 25858179
TI  - Depression and anxiety in expectant and new fathers: longitudinal findings in
      Australian men.
AB  - BACKGROUND: Despite growing interest in men's perinatal mental health, we still
      know little about whether becoming a new father is associated with increases in
      psychological distress. AIMS: To use prospective longitudinal data to investigate
      whether becoming a first-time expectant (partner pregnant) and/or new father
      (child <1 year) is associated with increases in depression and anxiety. METHOD:
      Men were aged 20-24 years at baseline (n = 1162). Levels of depression and
      anxiety were measured at four time points over 12 years. Over this time, 88 men
      were expectant fathers, 108 men were new fathers and 626 men remained non
      fathers. RESULTS: Longitudinal mixed models showed no significant increase in
      depression or anxiety as a function of expectant or new fatherhood, as compared
      with pre-fatherhood levels. CONCLUSIONS: Our findings suggest that, generally,
      expectant and new fathers are not at greater risk of depression or anxiety.
      Future epidemiological research should continue to identify men who are most (and
      least) at risk to focus resources and assistance most effectively.

PMID- 25858178
TI  - Evaluation of cognitive restructuring for post-traumatic stress disorder in
      people with severe mental illness.
AB  - BACKGROUND: A cognitive-behavioural therapy (CBT) programme designed for post
      traumatic stress disorder (PTSD) in people with severe mental illness, including
      breathing retraining, education and cognitive restructuring, was shown to be more
      effective than usual services. AIMS: To evaluate the incremental benefit of
      adding cognitive restructuring to the breathing retraining and education
      components of the CBT programme (trial registration: clinicaltrials.gov
      identifier: NCT00494650). METHOD: In all, 201 people with severe mental illness
      and PTSD were randomised to 12- to 16-session CBT or a 3-session brief treatment
      programme (breathing retraining and education). The primary outcome was PTSD
      symptom severity. Secondary outcomes were PTSD diagnosis, other symptoms,
      functioning and quality of life. RESULTS: There was greater improvement in PTSD
      symptoms and functioning in the CBT group than in the brief treatment group, with
      both groups improving on other outcomes and effects maintained 1-year post
      treatment. CONCLUSIONS: Cognitive restructuring has a significant impact beyond
      breathing retraining and education in the CBT programme, reducing PTSD symptoms
      and improving functioning in people with severe mental illness.

PMID- 25858180
TI  - Causal and mediating factors for anxiety, depression and well-being.
AB  - Background The relationship between well-being and mental ill health is complex;
      people may experience very low levels of well-being even in the absence of overt
      mental health problems. Aims This study tested the hypothesis that anxiety,
      depression and well-being have different causal determinants and psychological
      mediating mechanisms. Method The influence of causal and mediating factors on
      anxiety, depression and well-being were investigated in a cross-sectional online
      questionnaire survey hosted on a UK national broadcasting website. Results
      Multivariate conditional independence analysis of data from 27 397 participants
      revealed different association pathways for the two constructs. Anxiety and
      depression were associated with negative life events mediated by rumination; low
      levels of subjective well-being were associated with material deprivation and
      social isolation, mediated by adaptive coping style. Conclusions Our findings
      support the 'two continua' model of the relationship between psychological well
      being and mental health problems, with implications for both treatment and
      prevention. 

PMID- 25858181
TI  - Debriefing interventions for the prevention of psychological trauma in women
      following childbirth.
AB  - BACKGROUND: Childbirth is a complex life event that can be associated with both
      positive and negative psychological responses. When giving birth is experienced
      as particularly traumatic this can have a negative impact on a woman's postnatal
      emotional well-being. There has been an increasing focus on women's psychological
      trauma symptoms following childbirth, including the relatively rare phenomenon of
      post-traumatic stress disorder (PTSD), and the benefit of debriefing
      interventions to prevent this. In this review we examined the evidence for
      debriefing as a preventative intervention for psychological trauma following
      childbirth. OBJECTIVES: To assess the effects of debriefing interventions
      compared with standard postnatal care for the prevention of psychological trauma
      in women following childbirth. SEARCH METHODS: The trials registers of the
      Cochrane Depression, Anxiety and Neurosis Group (CCDANCTR-References and CCDANCTR
      Studies) and the Cochrane Pregnancy and Childbirth Group were searched up to 4
      March 2015. These registers include relevant randomised controlled trials from
      the following bibliographic databases: the Cochrane Library (all years to date),
      MEDLINE (1950 to date), EMBASE (1974 to date), and PsycINFO (1967 to date).
      Additional searches were conducted in CENTRAL, MEDLINE, EMBASE, PsycINFO, and
      Maternity and Infant Care. The reference lists of all included studies were
      checked for additional published reports and citations of unpublished research.
      Experts in the field were contacted. SELECTION CRITERIA: We included randomised
      controlled trials (RCTs) and quasi-randomised trials comparing postnatal
      debriefing interventions with standard postnatal care for the prevention of
      psychological trauma of women following childbirth. The intervention consisted of
      at least one debriefing intervention session, which had the purpose of allowing
      women to describe their experience and to normalise their emotional reaction to
      that experience. DATA COLLECTION AND ANALYSIS: Three authors independently
      assessed trial quality and extracted data. Meta-analysis was conducted where
      there were more than two trials examining the same outcomes. MAIN RESULTS: We
      included seven trials (eight articles) from three countries (UK, Australia and
      Sweden) that fulfilled the inclusion criteria. The number of women contributing
      data to each outcome varied from 102 to 1745. Methodological quality was variable
      and most of the studies were of low quality. The quality of evidence for the
      prevalence of psychological trauma (primary outcome) and the prevalence of
      depression symptoms was rated low or very low, based on few studies (ranging from
      a single study to three studies) with high risk of bias in main domains such as
      performance bias, random sequence generation, allocation concealment and
      incomplete outcome data. The quality of evidence for the remaining outcomes (that
      is prevalence of anxiety, prevalence of fear of childbirth, prevalence of general
      psychological morbidity, health service utilization and attrition from treatment)
      was not assessed as data were not available.Among women who had a high level of
      obstetric intervention during labour and birth, we found no difference between
      standard postnatal care with debriefing and standard postnatal care without
      debriefing on psychological trauma symptoms within three months postpartum (RR
      0.61; 95% CI 0.28 to 1.31; n = 425) or at three to six months postpartum (RR
      0.62; 95% CI 0.27 to 1.42; n = 246). The results were based on two trials,
      respectively. Among women who experienced a distressing or traumatic birth, there
      was no evidence of an effect of psychological debriefing on the prevention of
      PTSD (measured by the MINI-PTSD) at four to six weeks postpartum (RR 1.15; 95% CI
      0.66 to 2.01; n = 102) or at six months (RR 0.35; 95% CI 0.10 to 1.23; n = 103).
      The results were based on one small trial. One trial involving low-risk women who
      delivered healthy infants at or near term reported no significant difference
      between the intervention group and the control group in the proportion of women
      who met the diagnostic criteria for psychological trauma during the year
      following childbirth (RR 1.06; 95% CI 0.88 to 1.28; n = 1745). We did not find
      any information about attrition rates. AUTHORS' CONCLUSIONS: We did not find any
      high quality evidence to inform practice, with substantial heterogeneity being
      found between the studies conducted to date. There is little or no evidence to
      support either a positive or adverse effect of psychological debriefing for the
      prevention of psychological trauma in women following childbirth. There is no
      evidence to support routine debriefing for women who perceive giving birth as
      psychologically traumatic.Future research should provide greater detail of the
      outcome measures used, and with scales for measuring psychological trauma
      validated against clinical diagnostic interviews. High rates of obstetric
      intervention in some birth settings may mean that women require improved
      emotional care from health professionals to reduce the risk of childbirth being
      experienced as traumatic. As all included trials excluded women unable to
      communicate in the native language of the study setting, there is no information
      on the response of these women to psychological debriefing. No included studies
      were conducted in low or middle-income countries.

PMID- 25858182
TI  - Relative clinical effectiveness of carbon ion radiotherapy: theoretical modelling
      for H&N tumours.
AB  - Comparison of the efficiency of photon and carbon ion radiotherapy (RT)
      administered with the same number of fractions might be of limited clinical
      interest, since a wide range of fractionation patterns are used clinically today.
      Due to advanced photon treatment techniques, hypofractionation is becoming
      increasingly accepted for prostate and lung tumours, whereas patients with head
      and neck tumours still benefit from hyperfractionated treatments. In general, the
      number of fractions is considerably lower in carbon ion RT. A clinically relevant
      comparison would be between fractionation schedules that are optimal within each
      treatment modality category. In this in silico study, the relative clinical
      effectiveness (RCE) of carbon ions was investigated for human salivary gland
      tumours, assuming various radiation sensitivities related to their oxygenation.
      The results indicate that, for hypoxic tumours in the absence of reoxygenation,
      the RCE (defined as the ratio of D(50) for photons to carbon ions) ranges from
      3.5 to 5.7, corresponding to carbon ion treatments given in 36 and 3 fractions,
      respectively, and 30 fractions for photons. Assuming that interfraction local
      oxygenation changes take place, results for RCE are lower than that for an oxic
      tumour if only a few fractions of carbon ions are used. If the carbon ion
      treatment is given in more than 12 fractions, the RCE is larger for the hypoxic
      than for the well-oxygenated tumour. In conclusion, this study showed that in
      silico modelling enables the study of a wide range of factors in the clinical
      considerations and could be an important step towards individualisation of RT
      treatments.

PMID- 25858184
TI  - Analysis of microbiota in stable patients with chronic obstructive pulmonary
      disease.
AB  - To identify the bacterial diversity (microbiota) in expectorated sputum, a
      pyrosequencing method that investigates complex microbial communities of
      expectorated sputum was done in 19 stable chronic obstructive pulmonary disease
      patients (mean (SD) FEV1: 47 (18%) of predicted value). Using conventional
      culture, 3 phyla and 20 bacterial genera were identified, whereas the
      pyrosequencing approach detected 9 phyla and 43 genera (p < 0.001). In sputum the
      prevalent genera with pyrosequencing approach were Streptococcus, Actinomyces,
      Neisseria, Haemophilus, Rothia, Fusobacterium, Gemella, Granulicatella,
      Porphyromonas, Prevotella and Veillonella. Enterobacteriaceae, detected
      frequently in conventional culture, were not significantly detected with
      pyrosequencing methods. In addition, we found that important pathogens such as
      Haemophilus and Moraxella were detected more frequently with the new genetic
      procedures. The presence of Enterobacteriaceae is probably overestimated with
      conventional culture, whereas other difficult cultivable pathogens are
      underestimated. These studies open a new perspective for evaluating the role of
      bacterial colonization in chronic obstructive pulmonary disease pathogenesis and
      progression.

PMID- 25858183
TI  - Zinc regulates a switch between primary and alternative S18 ribosomal proteins in
      Mycobacterium tuberculosis.
AB  - The Mycobacterium tuberculosis genome encodes five putative 'alternative'
      ribosomal proteins whose expression is repressed at high Zn(2+) concentration.
      Each alternative protein has a primary homologue that is predicted to bind
      Zn(2+). We hypothesized that zinc triggers a switch between these paired
      homologous proteins and therefore chose one of these pairs, S18-1/S18-2, to study
      mechanisms of the predicted competition for their incorporation into ribosomes.
      Our data show that Zn(2+)-depletion causes accumulation of both S18-2 mRNA and
      protein. In contrast, S18-1 mRNA levels are unchanged to slightly elevated under
      Zn(2+)-limited conditions. However, the amount of S18-1 protein is markedly
      decreased. We further demonstrate that both S18 proteins interact with ribosomal
      protein S6, a committed step in ribosome biogenesis. Zn(2+) is absolutely
      required for the S18-1/S6 interaction while it is dispensable for S18-2/S6 dimer
      formation. These data suggest a model in which S18-1 is the dominant ribosome
      constituent in high zinc conditions, e.g. inside of phagosomes, but that it can
      be replaced by S18-2 when zinc is deficient, e.g. in the extracellular milieu.
      Consequently, Zn(2+)-depletion may serve as a signal for building alternative
      ribosomes when M. tuberculosis is released from macrophages, to allow survival in
      the extracellular environment.

PMID- 25858186
TI  - Surgery for melanoma is often delayed in Medicare patients, study finds.

PMID- 25858190
TI  - Secondary structure and folding stability of proteins adsorbed on silica
      particles - Pressure versus temperature denaturation.
AB  - We present a systematic study of the pressure and temperature dependent unfolding
      behavior of proteins that are adsorbed on silica particles. Hen egg white
      lysozyme and bovine ribonuclease A (RNase) were used as model proteins, and their
      secondary structures were resolved by Fourier transform infrared (FTIR)
      spectroscopy in the temperature range of 10-90 degrees C and the pressure range
      of 1-16,000bar. Apparently, the secondary structures of both proteins do not
      change significantly when they are adsorbing on the silica particles. Remarkably,
      the changes of the secondary structure elements upon protein unfolding are very
      similar in the adsorbed and the free states. This similarity could be observed
      for both lysozyme and RNase using both high pressures and high temperatures as
      denaturing conditions. However, the pressures and temperatures of unfolding of
      lysozyme and RNase are drastically lowered upon adsorption indicating lower
      folding stabilities of the proteins on the silica particles. Moreover, the
      temperature ranges, where changes in secondary structure occur, are broadened due
      to adsorption, which is related to smaller enthalpy changes of unfolding. For
      both proteins, free or adsorbed, pressure-induced unfolding always leads to less
      pronounced changes in secondary structure than temperature-induced unfolding. In
      the case of lysozyme, high pressure also favors a different unfolded conformation
      than high temperature. Overall, the results of this study reveal that adsorption
      of proteins on silica particles decreases the folding stability against high
      pressures and temperatures, whereas the unfolding pathways are mainly preserved
      in the adsorbed state. 

PMID- 25858192
TI  - Correction: Self-assembly of Janus particles under shear.

PMID- 25858191
TI  - Bio-templated bioactive glass particles with hierarchical macro-nano porous
      structure and drug delivery capability.
AB  - Hierarchically porous bioactive glass particles (BGPs) were synthesized by a
      facile sol-gel process using pollen grains as the templates. The synthesized
      pollen-templated bioactive glass particles (PBGPs) exhibited dual macro-nano
      porous structure. The macro pores (~ 1 MUm) were inherited from the template of
      pollen grains while the nano pores (~ 9.5 nm) were induced by the intrinsic
      mechanism of the sol-gel process. PBGPs possessed a high specific surface area
      (111.4m(2)/g) and pore volume (0.35 cm(3)/g). Hydroxyapatite (HA) formation on
      PBGPs was detected within 3 days after immersion in simulated body fluid (SBF).
      Due to their larger specific surface area and pore volume, PBGPs could be loaded
      with more tetracycline hydrochloride (TCH) than non-templated BGPs and
      conventional melt-derived 45S5 BGPs. In addition, PBGPs exhibited a low initial
      burst release (within 10% of the loaded amount) within 18 h and a sustained
      release with a two-stage release pattern for up to 6 days in phosphate buffered
      saline (PBS). The antibacterial assay confirmed that the TCH-loaded PBGPs could
      release TCH within 5 days, and the released TCH could reach the minimum
      inhibitory concentration (MIC) against Escherichia coli. MTT assay indicated that
      PBGPs showed non-cytotoxic effects toward human hepatocellular carcinoma (Hep G2)
      cells after co-culture for up to 72 h in vitro. These results showed that the
      biocompatible hierarchically macro-nano porous PBGPs are potential for bone
      regeneration and local drug delivery applications.

PMID- 25858193
TI  - Localized Health News Releases and Community Newspapers: A Method for Rural
      Health Promotion.
AB  - Newspaper health stories often originate with news releases from health
      organizations. Tailoring news releases to a particular mass media outlet
      increases the possibility that the release will result in a published story. This
      study describes a 2-year effort to promote coverage of health through
      dissemination of localized health news releases to newspapers. Each newspaper
      received stories tailored to that community. Localized elements of stories
      included local headlines and local data. Nearly half of newspapers in our study
      (48.2%) published at least one of our health news stories, and 541 health news
      stories were published as a result of the project. We also examined which types
      of newspapers were most likely to publish health news stories. Newspapers in
      rural versus suburban and urban areas were more likely to publish health news
      stories, as were midsized newspapers. In addition, rural newspapers were more
      likely than urban newspapers to publish stories about aging, specifically
      arthritis and heart disease. Our findings indicate that tailoring health news
      releases with local information and targeting releases to align with newspaper
      audience demographics could increase the quantity and quality of health-promoting
      information available to rural residents, who experience disparities in health
      care access and health outcomes. 

PMID- 25858194
TI  - Risk of Intracranial Hemorrhage From Statin Use in Asians: A Nationwide Cohort
      Study.
AB  - BACKGROUND: Reports of statin usage and increased risk of intracranial hemorrhage
      (ICH) have been inconsistent. This study examined potential associations between
      statin usage and the risk of ICH in subjects without a previous history of
      stroke. METHODS AND RESULTS: Patients initiating statin therapy between 2005 and
      2009 without a previous history of ischemic or hemorrhagic stroke were identified
      from Taiwan's National Health Insurance database. Participants were stratified by
      advanced age (>=70 years), sex, and diagnosed hypertension. The outcome of
      interest was hospital admission for ICH (International Classification of
      Diseases, Ninth Revision, Clinical Modification codes 430, 431, 432). Cox
      regression models were applied to estimate the hazard ratio of ICH. The
      cumulative statin dosage stratified by quartile and adjusted for baseline disease
      risk score served as the primary variable using the lowest quartile of cumulative
      dosage as a reference. There were 1 096 547 statin initiators with an average
      follow-up of 3.3 years. The adjusted hazard ratio for ICH between the highest and
      the lowest quartile was nonsignificant at 1.06 with a 95% confidence interval
      spanning 1.00 (0.94-1.19). Similar nonsignificant results were found in
      sensitivity analyses using different outcome definitions or model adjustments,
      reinforcing the robustness of the study findings. Subgroup analysis identified an
      excess of ICH frequency in patients without diagnosed hypertension (adjusted
      hazard ratio 1.36 [1.11-1.67]). CONCLUSIONS: In general, no association was
      observed between cumulative statin use and the risk of ICH among subjects without
      a previous history of stroke. An increased risk was identified among the
      nonhypertensive cohort, but this finding should be interpreted with caution.

PMID- 25858195
TI  - Studying the life course health consequences of childhood adversity: challenges
      and opportunities.

PMID- 25858197
TI  - A national tragedy: increases in death by suicide, decreases in other major
      causes of death.

PMID- 25858196
TI  - Adverse childhood experiences and blood pressure trajectories from childhood to
      young adulthood: the Georgia stress and Heart study.
AB  - BACKGROUND: The purposes of this study were to assess the long-term effect of
      adverse childhood experiences (ACEs) on blood pressure (BP) trajectories from
      childhood to young adulthood and to examine whether this relation is explained by
      childhood socioeconomic status (SES) or risk behaviors that are associated with
      ACEs. METHODS AND RESULTS: Systolic and diastolic BPs were measured up to 16
      times (13 times on average) over a 23-year period in 213 African Americans and
      181 European Americans 5 to 38 years of age. Retrospective data on traumatic
      experiences before 18 years of age were collected, including abuse, neglect, and
      household dysfunction. Individual growth curve modeling within a multilevel
      framework was used to examine the relation between exposure to ACEs and BP
      development. No main effect of ACEs on average BP levels was found. However, a
      significant interaction of ACE score with age(3) was observed (systolic BP,
      P=0.033; diastolic BP, P=0.017). Subjects who experienced multiple traumatic
      events during childhood showed a faster rise in BP levels after 30 years of age
      than those without ACEs. As expected, a graded association of ACEs with childhood
      socioeconomic status and negative health behaviors was observed (P<0.001). The
      ACE-systolic BP relation was not explained by these factors, whereas the ACE
      diastolic BP relation was partially mediated by illicit drug use. CONCLUSION: In
      this novel longitudinal study, we observed that participants who were exposed to
      multiple ACEs displayed a greater increase in BP levels in young adulthood
      compared with their counterparts without ACEs.

PMID- 25858198
TI  - The impact of a lifestyle change program on the mental health of obese under
      served African American women.
AB  - BACKGROUND: Obesity is a critical social and health issue, adversely impacting
      life expectancy, quality of life, and mental health. Minorities are
      disproportionately impacted by obesity with African Americans experiencing the
      highest prevalence among minority groups. PURPOSE: The aim of this study was to
      determine if a lifestyle program that integrated chair exercises, nutrition and
      educational counseling, and scripture readings would help under-served obese
      African American women make lifestyle changes that would positively impact their
      quality of life, especially mental health. METHODS: A repeated measures
      intervention study was conducted (24-weeks). Weeks 1-12 involved meeting twice a
      week for a total of 4h with participants engaged in chair exercises, educational
      counseling, and scripture readings. During weeks 13-24, the participants were "on
      their own" but were encouraged to exercise and eat healthy. Focus groups were
      held at 12 and 24-weeks. Participants were recruited from a nurse managed center
      and a primary care clinic for the uninsured. Mental health data were collected at
      baseline, 12, and 24-weeks. The Medical Outcomes Study Short Form Version 2 (SF
      36v2) was used to measure changes in mental health. Higher scores indicate better
      perceived health status. Group scores less than 47 indicate impaired functioning.
      FINDINGS: 55 women had complete data for all three data collection points, with a
      mean age of 50 and a mean BMI of 41.2. Repeated ANOVAs detected significant
      differences on the mental component summary of the SF-36v2: this score improved
      from baseline (M=44.1) to 12-weeks (M=50.7) but decreased at 24-weeks (M=47.9)
      (p=.000). The four domains (vitality, social functioning, role emotional, mental
      health) were also significantly different over the three data collection points.
      IMPLICATIONS: The findings have significant implications for psychiatric nurses
      in terms of education, clinical practice, and future research. The study
      contributed to the participants' mental health through the various group
      activities including scripture readings, socialization with "like minded" women
      and structured exercises. These findings offer psychiatric nurses additional
      tools for effective care.

PMID- 25858199
TI  - Obeah-illness versus psychiatric entities among jamaican immigrants: cultural and
      clinical perspectives for psychiatric mental health professionals.
AB  - In order to provide culturally authentic healthcare, psychiatric-mental health
      nurses and other professionals must familiarize themselves with the culture
      specific syndromes, idioms of distress, beliefs and practices that may present
      among the diverse patient groups with whom they work. Psychiatric conditions
      relating to the Jamaican belief in "Obeah" are specific, culturally-interpreted
      phenomena that psychiatric nurses may encounter among Jamaican patients. This
      paper describes the phenomenon of Obeah and its influences on the worldview of
      life, health, illness; psychiatric conditions in the form of culture-bound
      syndromes; and help-seeking behaviors throughout Jamaican cultural communities.
      Inability to understand the obeah-illness concept from a culturally-interpreted
      perspective may be constrictive and result in less-than-optimal care. Armed with
      the knowledge of the concept of Obeah from a core belief perspective, how it
      influences psychiatric presentations, and embracing its significance to the
      Jamaican health belief model will assist in building a workable, caring, best
      practice framework aimed toward a clinical and practice paradigm for this unique
      folk-health belief system. 

PMID- 25858200
TI  - Effects of teaching communication skills using a video clip on a smart phone on
      communication competence and emotional intelligence in nursing students.
AB  - This study aims to verify the communication skills training for nursing students
      by using a video clip on a smart phone. The study settings were the nursing
      departments of two universities in South Korea. This study was a quasi
      experimental one using a nonequivalent control group pre-posttest design. The
      experimental and control groups consisted of second-year nursing students who had
      taken a communication course. The experimental group included 45 students, and
      the control group included 42 students. The experimental group improved more
      significantly than the control group in communication competence and emotional
      intelligence. Using a video clip on a smart phone is helpful for communication
      teaching method. 

PMID- 25858201
TI  - 'You just lose the people you know': relationship loss and mental illness.
AB  - The purpose of this qualitative study was to explore the nature, scope and
      consequences of losses resulting from mental illness. This paper presents
      findings from a key theme of this study-the loss of relationships. Thematic
      analysis revealed two categories: loss of intimate relationships, which included
      subcategories of (i) spouses/partners, (ii) children/parenthood, (iii) family,
      and (iv) friends; and (2) people within the community, such as people at church
      and support groups. Relationships are seen as one of the most crucial yet
      challenging elements to recovery and wellbeing for people affected by mental
      illness. 

PMID- 25858202
TI  - The effects of dietary tryptophan on affective disorders.
AB  - Using a randomized crossover study design, 25 healthy young adults were examined
      for differences in anxiety, depression, and mood after consuming a high
      tryptophan and a low tryptophan diet for 4days each. There was a 2week washout
      between the diets. A within-subjects analysis of the participants' mood indicated
      significantly (p<.01) more positive affect scores after consuming a high
      tryptophan diet as compared to a low tryptophan diet. Negative affect differences
      between the diets were not statistically significant (p>.05). Also, consuming
      more dietary tryptophan resulted in (p<.05) less depressive symptoms and
      decreased anxiety. 

PMID- 25858203
TI  - The effect of positive group psychotherapy on self-esteem and state anger among
      adolescents at Korean immigrant churches.
AB  - The aim of the current study was to describe participants' experiences and
      examine the effects of group therapy on self-esteem and state anger among the
      adolescent children of immigrants in the US. A quasi-experimental design and
      qualitative and quantitative methods were used. Group therapy was conducted for
      8weeks. Thirty-three adolescents took part in the study. Quantitative results
      revealed that group therapy improved self-esteem (t=2.222. p<.05) but not state
      anger. However, qualitative results suggested that group therapy helped improve
      interpersonal relationships and communication skills, the forgiveness of others,
      and the management of anger. Furthermore, group therapy utilizing positive
      psychology strategies improved self-esteem, interpersonal relationships, and
      communication skills. 

PMID- 25858204
TI  - Exploring identity dynamics in mental help-seeking trajectories: an ethnographic
      study among inpatient service users of two Belgian psychiatric hospitals.
AB  - Using an ethnographic approach, in combining interviews with forty-two inpatient
      service users and participant observations, this research explored service users'
      experiences of their help seeking trajectories in an effort to uncover identity
      dynamics by which these are informed. They described both identity dynamics that
      made them postpone their search for help, like their belief in the essential
      difference between themselves and mental health service users; and dynamics that
      catalyzed their hospitalization, like the loss of social roles. Their accounts
      illustrate how experiences of barriers and facilitators for help seeking are
      closely intertwined with identity and therefore context related dynamics. 

PMID- 25858205
TI  - Effectiveness of the tobacco tactics program for psychiatric inpatient veterans:
      an implementation study.
AB  - BACKGROUND: The objective of this study was to evaluate the effectiveness of the
      inpatient, nurse-administered Tobacco Tactics program for patients admitted for
      psychiatric conditions in two Veterans Affairs (VA) hospitals compared to a
      control hospital. METHODS: This is a subgroup analysis of data from the inpatient
      tobacco tactics effectiveness trial, which was a longitudinal, pre- post
      nonrandomized comparison design with 6-month follow-up in the three large
      Veterans Integrated Service Networks (VISN) 11 hospitals. RESULTS: Six-month self
      reported quit rates for patients admitted for psychiatric conditions increased
      from 3.5% pre-intervention to 10.2% post-intervention compared to a decrease in
      self-reported quit rates in the control hospital (12% pre-intervention to 1.6%
      post-intervention). There was significant improvement in self-reported quit rates
      for the pre- versus post-intervention time periods in the Detroit and Ann Arbor
      intervention sites compared to the Indianapolis control site (P=0.01) and
      cotinine results were in the same direction. CONCLUSION: The implementation of
      the Tobacco Tactics intervention has the potential to significantly decrease
      smoking and smoking-related morbidity and mortality among smokers admitted to VA
      hospitals for psychiatric disorders.

PMID- 25858206
TI  - Experiences of community-dwelling persons recovering from severe mental illness.
AB  - This qualitative study explored experiences of recovery from severe mental
      illness based on semi-structured interviews with sixteen persons diagnosed with
      schizophrenia spectrum disorders using psychiatric rehabilitation facilities. The
      participants' transcripts revealed two major themes: (1) ongoing efforts to live
      better and (2) inconsistent self-acceptance as a person living with a mental
      illness. The participants were aware of their responsibility to live with
      integrity. They all had hopes and goals, were able to respond to social cues, and
      considered what they could do independently. They wanted to be recognized as
      people who adapted successfully in society while inconsistently perceiving
      themselves as either sick or healthy. It is necessary to examine approaches that
      support the identities of persons who have been treated for schizophrenia and
      allow them to live comfortable within their communities. 

PMID- 25858207
TI  - Strongly correlated plexcitonics: evolution of the Fano resonance in the presence
      of Kondo correlations.
AB  - We study the optical absorption of a system consisting of a diatomic molecule
      that exhibits strong electron correlations coupled to metal nanoparticles
      possessing plasmon resonances by invoking the time-dependent non-crossing
      approximation. We investigate the evolution of the Fano resonance arising from
      the plasmon-exciton coupling when both atoms are Coulomb blockaded. We found that
      the Fano resonance rapidly dwindles as the ambient temperature exceeds the Kondo
      temperature of the singly occupied discrete state with higher energy and vanishes
      entirely at elevated temperatures. Our results show that even boosting the
      plasmon-exciton coupling above this temperature scale fails to revive the Fano
      resonance. We propose a microscopic model that accounts for these results. We
      suggest that a possible remedy for observation of the Fano resonance at high
      ambient temperatures is to position the singly occupied discrete state with the
      higher energy as close as possible to the Fermi level of the contacts while
      keeping the emitter resonance constant to prevent the merger of the Fano and
      plasmon resonances. 

PMID- 25858208
TI  - Systematic review: thalidomide and thalidomide analogues for treatment of
      inflammatory bowel disease.
AB  - BACKGROUND: It has been reported that thalidomide may be effective in treating
      inflammatory bowel disease (IBD). AIM: To review the evidence examining the
      efficacy and safety of thalidomide for inducing and maintaining remission in
      Crohn's disease (CD) and ulcerative colitis (UC). METHODS: The Cochrane Central
      Register of Controlled Trials (CENTRAL), MEDLINE, PubMed (1950-August 2014),
      EMBASE (1984-August 2014), Scopus, and Web of knowledge were searched for
      randomised controlled trials (RCTs), observational studies and case series. The
      primary outcomes were induction of remission or response for active IBD or
      relapse rate for patients in remission and subsequently on thalidomide/analogues
      for at least 3 months. RESULTS: Twelve studies (2 RCTs and 10 case series) met
      the inclusion criteria for inducing remission and included 248 patients (10 with
      UC, 238 with CD). Only one RCT of paediatric CD achieved high quality scores
      (remission rate thalidomide: 46%, placebo: 12%; p=0.01). The crude pooled
      remission rate for thalidomide was 49% and 25% in luminal and perianal CD
      respectively. For UC, 50% achieved remission and 10% had partial response. One
      case series reported 21 patients (17 CD, four UC) who maintained remission for 6
      months. Many adverse events were reported including sedation (32%) and peripheral
      neuropathy (20%). CONCLUSIONS: One high quality RCT showed that thalidomide is
      effective for inducing remission in paediatric CD. The current evidence is
      insufficient to support using thalidomide to induce remission in UC or adult CD,
      or to maintain remission in IBD. Significant adverse events may occur,
      necessitating discontinuation of thalidomide.

PMID- 25858209
TI  - Stable thermoplastic, pressure-formed record bases.

PMID- 25858210
TI  - Optimal placement of the two anterior implants for the mandibular All-on-4
      concept.
AB  - The novelty of the All-on-4 concept for a mandibular implant-supported fixed
      dental prosthesis is the inclination of the posterior implants. Typically, the
      anterior implants are placed lingually relative to the canine/incisor teeth and
      perpendicular relative to the occlusal plane. According to the laws of elementary
      biomechanics, the long axis of the implant unit should be aligned to the axis of
      the occlusal loading forces during clenching in the maximal intercuspal position.
      When several implants are connected by a prosthesis, the mean axis of the overall
      occlusal loading must be taken into account. The objective of this report was to
      propose a different position for anterior implants by tilting them labially to
      counterbalance the distal inclination of the posterior implants.

PMID- 25858211
TI  - Maxillofacial prosthodontic rehabilitation of a patient with oral complications
      during and after multimodality therapy for the management of oral squamous cell
      carcinoma.
AB  - Multimodality cancer therapy involving surgical resection, chemotherapy, and
      radiation therapy is frequently employed in the management of head and neck
      cancer. Patients who have undergone such therapy face substantial challenges
      during and after treatment. Prosthodontic rehabilitation is essential during and
      after tumor ablation to restore function, esthetics, and minimize interruption in
      daily routine. This clinical report describes the challenges faced by a patient
      undergoing multimodality therapy for a squamous cell carcinoma of the maxillary
      sinus and the stages involved in prosthodontic rehabilitation. 

PMID- 25858212
TI  - Reporting numeric values of complete crowns. Part 1: Clinical preparation
      parameters.
AB  - STATEMENT OF PROBLEM: An implemented objective measuring system for measuring
      clinical tooth preparations does not exist. PURPOSE: The purpose of this study
      was to compare clinically achieved tooth preparations for ceramic crowns by
      general dentists with the recommended values in the literature with an objective
      measuring method. MATERIAL AND METHODS: Two hundred thirty-six stone dies
      prepared for anterior and posterior complete ceramic crown restorations (IPS
      e.max Press; Ivoclar Vivadent) were collected from dental laboratories. The dies
      were scanned and analyzed using the coordinate geometry method. Cross-sectioned
      images were captured, and the average total occlusal convergence angle, margin
      width, and abutment height for each preparation was measured and presented with
      associated 95% confidence intervals. RESULTS: The average total occlusal
      convergence angles for each tooth type was above the recommended values reported
      in the literature. The average margin widths (0.40 to 0.83 mm) were below the
      minimum recommended values (1 to 1.5 mm). The tallest preparations were maxillary
      canines (5.25 mm), while the shortest preparations were mandibular molars (1.87
      mm). CONCLUSIONS: Complete crown preparations produced in general practice do not
      achieve the recommended values found in the literature. However, these
      recommended values are not based on clinical trials, and the effects of observed
      shortfalls on the clinical longevity of these restorations are not predictable.

PMID- 25858213
TI  - An adjustable, cast based, fully restrictive surgical guide.
AB  - The 3D Click Guide is a fully restrictive cast-based surgical guide for the
      placement of dental implants. This in-office system consists of prefabricated
      parts that are assembled onto a carrier. The 3-dimensional data are derived from
      a dental cast in combination with a periapical radiograph or cone-beam computed
      tomography data.

PMID- 25858214
TI  - Biofilms in restorative dentistry: A clinical report.
AB  - This clinical report describes the structure and characteristics of the biofilm
      formed under a cemented restoration, confirming the need to develop new
      cementation protocols to disrupt and minimize the formation of biofilm before
      cementing definitive restorations. 

PMID- 25858215
TI  - Biometric analysis of the clinical crown and the width/length ratio in the
      maxillary anterior region.
AB  - STATEMENT OF PROBLEM: Restorative dentistry often involves correcting tooth size
      discrepancies. Therefore, dental biometrics should play an important role in the
      planning of an esthetic restoration. PURPOSE: The purpose of this study was to
      analyze the clinical crown width, length, and width/length ratio of maxillary
      central incisors, lateral incisors, and canines in an adult population. The study
      also aimed to determine whether a correlation exists between natural tooth
      dimensions and the optimal tooth dimension guidelines suggested for planning
      esthetic restorations. MATERIAL AND METHODS: Stone casts were poured from
      irreversible hydrocolloid impressions of 412 healthy adult participants. These
      casts were used to measure the maximum mesiodistal width and maximum crown-root
      length of the maxillary central incisors, lateral incisors, and canines with a
      digital precision caliper (0.01 mm). The width/length ratio was calculated for
      each tooth, and 40 casts were selected to test the reliability of the measuring
      method. RESULTS: The mean age of the participants in the sample was 33.94 years;
      60.7% were women and 39.3% were men. The mean width value was 8.71 mm for central
      incisors, 6.75 mm for lateral incisors, and 7.81 mm for canines. The mean length
      was 10.23 mm for central incisors, 8.59 mm for lateral incisors, and 9.93 mm for
      canines. The average width/length ratio was 85% for central incisors and 79% for
      lateral incisors and canines. CONCLUSION: The data obtained from the population
      studied are similar to those from previous research studies with similar
      methodology. However, great discrepancies in the absolute values were found when
      compared with other studies of ideal tooth dimension guidelines on the personal
      preferences and the esthetic perception of dentists. The perception of what is
      considered natural seems to differ from what is considered esthetically perfect.

PMID- 25858216
TI  - A technique for changing the shade of a custom-made ocular prosthesis.

PMID- 25858217
TI  - Reporting numeric values of complete crowns. Part 2: Retention and resistance
      theories.
AB  - STATEMENT OF PROBLEM: Determining the retention and resistance of a tooth
      preparation for a complete crown has only existed in theory, and these theories
      have never been measured on tooth preparations performed in vivo. PURPOSE: The
      purpose of this study was to measure the theoretical retention and resistance of
      clinically produced complete crown preparations by using an objective measuring
      method. MATERIAL AND METHODS: Stone dies from 236 complete crown preparations
      were collected from dental laboratories. The dies were scanned and analyzed with
      the coordinate geometry method. Cross-sectional images were captured, and the
      surface area was measured with a cone frustum and right truncated pyramid
      formula. Two different theories of resistance form, the "on" or "off" theory
      (limiting taper) and the linear model (resistance length), were calculated for
      premolar and molar preparations. RESULTS: The mean surface areas ranged from
      33.97 mm(2) to 105.44 mm(2) for the cone frustum formula and 41.75 mm(2) to
      117.50 mm(2) for the right truncated pyramid formula. The facial side of
      maxillary premolars exhibited the highest percentage of resistance form with the
      limiting taper, at 58%, and the mesial side of the mandibular molars exhibited
      the lowest percentage of resistance form, at 6%. CONCLUSIONS: The objective
      method used in this study provides a way for retention and resistance theories to
      be tested and for further clinical implications to be investigated.

PMID- 25858218
TI  - Comparison of marginal and internal fit of press-on-metal and conventional
      ceramic systems for three- and four-unit implant-supported partial fixed dental
      prostheses: An in vitro study.
AB  - STATEMENT OF PROBLEM: Adaptation is an important factor in the long-term clinical
      success of implant supported ceramic restorations. Ceramic firings may affect the
      adaptation of the restoration. PURPOSE: The purpose of this study was to compare
      the marginal and internal adaptation of 3 different restorative materials and the
      effect of veneering/pressing on the material used for 3- and 4-unit implant
      supported fixed dental prostheses. MATERIAL AND METHODS: One mandibular epoxy
      cast was prepared for 3-unit restorations and one for 4-unit restorations.
      Impressions of the casts were made and 60 stone die casts (30 3-unit, 30 4-unit)
      produced. The casts were divided into 3 subgroups: group MCR, conventional metal
      ceramic restorations; group POM, press-on-metal restorations; group ZIR, computer
      aided design/computer-aided manufacturing CAD/CAM) zirconia restorations. A
      replica technique was used to examine the marginal and internal gap values. A
      total of 2400 measurements were made by making 40 measurements of each
      restoration. The data were evaluated statistically using analysis of variance and
      the least significant difference post hoc test (alpha=.05). RESULTS: The lowest
      marginal gaps were found in group POM (81.58 MUm) and the highest in group MCR
      (103.82 MUm). The differences in marginal adaptation measurements were found to
      be statistically significant. The highest values for internal adaptation were
      found at the occlusal surface in all groups. CONCLUSIONS: Although veneering
      metal ceramic restorations increased the misfit of the restoration, the marginal
      discrepancy of the materials (81 to 120 MUm) can be considered clinically
      acceptable.

PMID- 25858219
TI  - Influence of coloring procedure on flexural resistance of zirconia blocks.
AB  - STATEMENT OF PROBLEM: The white color of zirconia limits the possibility of a
      natural-looking restoration. Industrially precolored blocks and green-stage
      coloring liquids are used to obtain shaded zirconia. Several authors have
      reported that pigments may negatively affect the mechanical characteristics of
      the material. PURPOSE: The purpose of this in vitro study was to investigate the
      effect of a recently marketed coloring system on the flexural strength (sigma),
      Weibull characteristic strength (sigma0), and Weibull modulus (m) of a zirconia
      for computer-aided design/computer-aided manufacturing (CAD/CAM) systems.
      MATERIAL AND METHODS: Noncolored white blocks (In-Ceram YZ), industrially
      precolored blocks (In-Ceram YZ col. LL1p), and green-stage infiltration-shaded
      blocks in 4 colors (In-Ceram YZ Coloring Liquids) were tested. Industrially
      precolored specimens (n = 30) were assigned to the PREC group. Noncolored
      specimens were divided into 5 groups (n = 30). Group CNTR was not treated
      (control). Groups INF-N, INF-L, INF-M, and INF-I were subject to green-stage
      infiltration (neutral, light, medium, and intense, respectively). Specimens were
      tested in a 3-point bending apparatus following ISO 6872:2008 specifications.
      Data were analyzed by 1-way ANOVA. RESULTS: The calculated flexural strengths
      (MPa) were CNTR 1232.56 +/- 103.91; PREC 1215.16 +/- 141.42; INF-N 1280.72 +/-
      160.10; INF-L 1218.92 +/- 78.63; INF-M 1153.71 +/- 176.80; and INF-I 1248.46 +/-
      111.73. No statistically significant differences were found among the tested
      groups (P = .195). CONCLUSIONS: Unlike what has been reported for other
      combinations of zirconia and coloring liquids, the coloring technique tested in
      the present study did not negatively influence the flexural characteristics of
      the tested zirconia.

PMID- 25858220
TI  - Comparison of a conventional and virtual occlusal record.
AB  - STATEMENT OF PROBLEM: Conventional methods associated with many processes in
      dentistry are being replaced by methods that use digital technology. One of these
      processes is the making of occlusal records for the positioning of casts in a
      virtual articulator. Conventional interocclusal records and the articulator are
      being replaced by the virtual occlusal record and the virtual articulator.
      PURPOSE: The purpose of this study was to validate a virtual procedure to locate
      the mandibular cast in a 3-dimensional (3D) spatial position and to verify the
      occlusal contact points in reference to the corresponding maxillary cast on a
      virtual articulator. MATERIAL AND METHODS: The conventional procedure was carried
      out by locating 6 sets of casts in maximal intercuspal position without any
      interocclusal record. Then, the occlusal contacts were determined with
      articulating paper. Subsequently, the occlusal relationships and stone cast were
      digitized with a 3D scanner. The occlusal contacts were compared with photographs
      and by superimposing these on screenshots of the software. Finally, the deviation
      of discrete points on the mandibular cast was calculated, and all the points of
      the occlusal surface were compared point by point. RESULTS: This study analyzed
      the main variables of the virtual occlusal record by using 3 current reverse
      engineering software packages. The results show a mean deviation of 0.069 mm from
      the virtual occlusion procedure and a mean standard deviation of 0.011 mm from
      all the points of the occlusal surface. CONCLUSIONS: The main conclusion of this
      study was that the accuracy provided by a virtual occlusion procedure is greater
      than that of the traditional physical interocclusal record. Additionally, knowing
      the deviation of each alignment (best-fit operation or algorithm) is useful.

PMID- 25858221
TI  - Adhesive retention of experimental fiber-reinforced composite, orthodontic
      acrylic resin, and aliphatic urethane acrylate to silicone elastomer for
      maxillofacial prostheses.
AB  - STATEMENT OF PROBLEM: A key factor of an implant-retained facial prosthesis is
      the success of the bonding between the substructure and the silicone elastomer.
      Little has been reported on the bonding of fiber reinforced composite (FRC) to
      silicone elastomers. Experimental FRC could be a solution for facial prostheses
      supported by light-activated aliphatic urethane acrylate, orthodontic acrylic
      resin, or commercially available FRCs. PURPOSE: The purpose of this study was to
      evaluate the bonding of the experimental FRC, orthodontic acrylic resin, and
      light-activated aliphatic urethane acrylate to a commercially available high
      temperature vulcanizing silicone elastomer. MATERIAL AND METHODS: Shear and 180
      degree peel bond strengths of 3 different substructures (experimental FRC,
      orthodontic acrylic resin, light-activated aliphatic urethane acrylate) (n=15) to
      a high-temperature vulcanizing maxillofacial silicone elastomer (M511) with a
      primer (G611) were assessed after 200 hours of accelerated artificial light
      aging. The specimens were tested in a universal testing machine at a cross-head
      speed of 10 mm/min. Data were collected and statistically analyzed by 1-way
      ANOVA, followed by the Bonferroni correction and the Dunnett post hoc test
      (alpha=.05). Modes of failure were visually determined and categorized as
      adhesive, cohesive, or mixed and were statistically analyzed with the chi-squared
      goodness-of-fit test (alpha=.05). RESULTS: As the mean shear bond strength values
      were evaluated statistically, no difference was found among the experimental FRC,
      aliphatic urethane acrylate, and orthodontic acrylic resin subgroups (P>.05). The
      mean peel bond strengths of experimental fiber reinforced composite and aliphatic
      urethane acrylate were not found to be statistically different (P>.05). The mean
      value of the orthodontic acrylic resin subgroup peel bond strength was found to
      be statistically lower (P<.05). Shear test failure types were found to be
      statistically different (P<.05), whereas 180-degree peel test failure types were
      not found to be statistically significant (P>.05). Shear forces predominantly
      exhibited cohesive failure (64.4%), whereas peel forces predominantly exhibited
      adhesive failure (93.3%). CONCLUSION: The mean shear bond strengths of the
      experimental FRC and aliphatic urethane acrylate groups were not found to be
      statistically different (P>.05). The mean value of the 180-degree peel strength
      of the orthodontic acrylic resin group was found to be lower (P<.05).

PMID- 25858222
TI  - Long-term clinical evaluation of the color stability and stainability of acrylic
      resin denture teeth.
AB  - STATEMENT OF PROBLEM: The color stability and staining of acrylic resin denture
      teeth remains an esthetic problem for complete denture wearers. PURPOSE: The
      purpose of this study was to evaluate the long-term clinical color stability and
      stainability of acrylic resin denture teeth in complete denture wearers over a
      period of 5 years. MATERIAL AND METHODS: Fifty participants rehabilitated with
      complete dentures from February 2008 to December 2013 were selected. The
      demographic data and the clinical characteristics of participants were recorded.
      Color change (DeltaE) in 3 regions of the denture teeth (incisal, middle, and
      cervical) was evaluated by spectrophotometry in the CIE L*a*b* system.
      Participants were asked whether they had noticed any changes in the coloring of
      the teeth in their dentures. Hierarchical clustering analysis was used to
      identify groups formed from variables related to demographic questions and color
      analysis. Two-way ANOVA among the color cluster groups was performed and the
      Tukey-Kramer test was used as a post hoc test (alpha=.05). A chi-square test and
      Fisher exact test were used to identify the association between the study
      variables and color changes in the participants' responses (alpha=.05). RESULTS:
      Four cluster groups from 50 participants were identified in the clustering
      analysis. The DeltaE was statistically significant for the interaction between
      the dental third and cluster groups (P<.001). Cluster groups 1 and 4 exhibited
      statistically higher DeltaE values than cluster groups 2 and 3 (P<.05). Greater
      chromatic alterations were noted in the incisal third of the teeth than in the
      cervical and medium thirds in the cluster groups 1 (DeltaE=11.03 +/-1.22) and 3
      (DeltaE=4.14 +/-1.14) (P<.05). No relationship was found with the participants'
      personal opinions about color change (P>.05). CONCLUSION: Although the acrylic
      resin denture teeth exhibited color instability and staining in vivo, the
      participants were unable to identify the color change. The cluster groups with
      higher color change values consumed more staining solutions.

PMID- 25858223
TI  - Limiting the dimension of a screw-access hole with an interim screw-retained
      prosthesis.
AB  - Fabricating an interim screw-retained prosthesis often involves obliteration of
      the abutment screw access site, which later must be exposed. This frequently
      results in excessive preparation of the screw access site with poor esthetics and
      a weaker restoration. The technique described expedites the process by locating
      the access site and limits the size of the screw access hole preparation. 

PMID- 25858224
TI  - Consequences of relining on a maxillary complete denture: A clinical report.
AB  - The position of a complete denture may change after relining, especially in the
      maxillary arch. This report reviews relining techniques and presents a situation
      with anterior displacement after the relining of a maxillary complete denture.
      Instead of providing a new denture, the displaced denture was repaired and the
      original tooth arrangement maintained. 

PMID- 25858225
TI  - Comparison of the metal-ceramic bond after recasting and after laser sintering.
AB  - STATEMENT OF PROBLEM: Failure of the bond between metal and ceramic is common
      with metal ceramic prostheses. PURPOSE: The purpose of this in vitro study was to
      investigate how recasting affects the metal-ceramic bond strength for 1 base
      metal and 1 noble alloy compared with laser-sintered Co-Cr alloy by using a
      procedure based on ANSI/ADA Specification No. 38. MATERIAL AND METHODS: One laser
      sintered (Co-Cr) and 2 metal (Co-Cr, Pd-Ag) alloys were used. Metal strips (25 *
      3 * 0.5 mm) were obtained with 2 different methods: torch melting and laser
      sintering. Twelve alloy specimens were processed for each group. Vita VM13
      porcelain layers (8 * 3 * 1.1 mm) were fabricated at the centers of the metal
      frameworks. Specimens containing 100% fresh alloy were used in the first casting
      group (control). Metal ceramic specimens were prepared for each alloy, and no new
      metal was added to the second and third castings. The findings were statistically
      analyzed and compared with a 2-way analysis of variance (ANOVA). RESULTS: The
      second casting of the noble alloy-ceramic specimen had the highest mean metal
      ceramic bond strength in flexure. No significant differences were found between
      the laser-sintered Co-Cr and the Pd-Ag metal ceramic specimens after the first
      and third castings. CONCLUSION: All groups had adequate porcelain bond strength,
      except C2 (second casting of Co-Cr alloy) and C3 (third casting of Co-Cr alloy).
      Co-Cr alloy fabricated with new laser-sintering techniques is a promising
      alternative for metal ceramic restorations. Further research is needed before its
      use can be advocated in the dental laboratory.

PMID- 25858226
TI  - Effect of surface treatments on the biaxial flexural strength, phase
      transformation, and surface roughness of bilayered porcelain/zirconia dental
      ceramics.
AB  - STATEMENT OF PROBLEM: Veneered zirconia restorations are widely used in
      prosthetic applications. However, these restorations often fail because of
      chipping of the veneer porcelain. Surface treatments of zirconia core materials
      may affect the connection between the 2 layers. PURPOSE: The purpose of this
      study was to evaluate the effect of surface treatments on the biaxial flexural
      strength, phase transformation, and mean surface roughness of different bilayered
      porcelain/zirconia ceramics. MATERIAL AND METHODS: Forty disk-shaped specimens
      were obtained for each material (Kavo and Noritake) and divided into 4 (n=10)
      groups (control, airborne-particle abraded, ground, and ground and airborne
      particle abraded). Airborne-particle abrasion was performed with 110-MUm Al2O3
      particles for 15 seconds and at 400 kPa. Diamond rotary instruments with 100-MUm
      grain size were used for grinding. The monoclinic phase transformation and
      surface roughness of the specimens were measured. Then, the specimens were
      veneered and subjected to a biaxial flexural strength test to calculate the
      Weibull moduli (m values) and the stresses occurring at the layers, outer
      surfaces of the bilayer, and interfaces of the layers. RESULTS: The Kavo airborne
      particle abraded group showed higher strength values in both layers (P<.05) than
      those of all experimental groups. The Kavo airborne-particle abraded group showed
      the lowest m values at the core and veneer layers. According to the phase
      analysis, significantly higher Xm values were found in the ground and airborne
      particle abraded groups for both materials (P<.05). In both materials, except in
      the airborne-particle abraded groups, the relative monoclinic phases showed no
      difference (P<.05). CONCLUSION: Surface treatments affected the phase
      transformation, surface roughness, and biaxial flexural strength of Kavo and
      Noritake zirconia ceramics differently. Surface treatments increased the relative
      monoclinic phase content and average surface roughness.

PMID- 25858227
TI  - Induction of Th17 cells by segmented filamentous bacteria in the murine
      intestine.
AB  - Segmented filamentous bacteria (SFB) are Gram-positive, anaerobic, spore-forming
      commensals that reside in the gut of many animal species. Described more than
      forty years ago, SFB have recently gained interest due to their unique ability to
      modulate the host immune system through induction of IgA and Th17 cells. Here, we
      describe a collection of methods to detect and quantify SFB and SFB adhesion in
      intestinal mucosa, as well as SFB-specific CD4 T cells in the lamina propria. In
      addition, we describe methods for purification of SFB from fecal material of SFB
      monoassociated gnotobiotic mice. Using these methods we examine the kinetics of
      SFB colonization and Th17 cell induction. We also show that SFB colonize unevenly
      the intestinal mucosa and that SFB adherence occurs predominantly in the terminal
      ileum and correlates with an increased proportion of SFB-specific Th17 cells. 

PMID- 25858228
TI  - Using image-based flow cytometry to measure monocyte oxidized LDL phagocytosis: A
      potential risk factor for CVD?
AB  - Obesity and cardiovascular disease is a worldwide health concern that has been a
      major focus in research for several decades. Among these diseases,
      atherosclerosis is one of the leading causes of death and disability nationwide.
      Circulating monocytes are believed to be primary cells responsible for foam cell
      formation. The present report describes a novel method for measuring monocyte
      oxLDL phagocytosis capacity using image-based flow cytometry. Human venous blood
      monocytes were incubated with different concentrations of oxLDL for different
      lengths of time to optimize the assay. High (post-meal) and low (pre-meal)
      responder samples were generated by feeding human subjects a high-fat (~85% of
      daily fat allowance), high-calorie (~65% of daily calorie needs) meal. This is a
      relevant model with respect to obesity and risk of developing atherogenesis.
      After the functional assay, classic (CD14+/CD16-) and pro-inflammatory
      (CD14+/CD16+) monocytes were assessed for oxLDL uptake, adhesion molecule
      expression (CD11b and CD18), and scavenger receptor expression (CD36) using an
      image-based flow cytometer (FlowSight). The present method represents a novel
      advance in methods available to detect the propensity of circulating monocytes to
      become intima foam cells. We found the assay to be most effective at separating
      high from low responder samples when using a fixed oxLDL concentration (120
      MUL/mL) and incubation length (1-h). In a clinical application, this method
      demonstrated that consuming a single high-fat meal causes an increase in the
      proportion of monocyte oxLDL phagocytosis and their adhesion capacity, suggesting
      a higher propensity to become foam cells.

PMID- 25858229
TI  - Imaging flow cytometry for the study of erythroid cell biology and pathology.
AB  - Erythroid cell maturation and diseases affecting erythrocytes are frequently
      accompanied by morphologic and immunophenotypic changes to these cells. In the
      past, these changes have been assessed primarily through the use of manual
      microscopy, which substantially limits the statistical rigor, throughput, and
      objectivity of these studies. Imaging flow cytometry provides a technology to
      examine both the morphology of cells as well as to quantify the staining
      intensity and signal distribution of numerous fluorescent markers on a cell-by
      cell basis with high throughput in a statistically robust manner, and thus is
      ideally suited to studying erythroid cell biology. To date imaging flow cytometry
      has been used to study erythrocytes in three areas: 1) erythroid cell maturation,
      2) sickle cell disease, and 3) infectious diseases such as malaria. In the
      maturation studies, imaging flow cytometry can closely recapitulate known stages
      of maturation and has led to the identification of a new population of erythroid
      cell precursors. In sickle cell disease, imaging flow cytometry provides a robust
      method to quantify sickled erythrocytes and to identify cellular aggregates
      linked to morbidities, and in malaria, imaging flow cytometry has been used to
      screen for new chemotherapeutic agents. These studies have demonstrated the value
      of imaging flow cytometry for investigations of erythrocyte biology and
      pathology. 

PMID- 25858230
TI  - Vaccines for visceral leishmaniasis: A review.
AB  - Visceral leishmaniasis, which is also known as Kala-Azar, is one of the most
      severely neglected tropical diseases recognized by the World Health Organization
      (WHO). The threat of this debilitating disease continues due to unavailability of
      promising drug therapy or human vaccine. An extensive research is undergoing to
      develop a promising vaccine to prevent this devastating disease. In this review
      we compiled the findings of recent research with a view to facilitate knowledge
      on experimental vaccinology for visceral leishmaniasis. Various killed or
      attenuated parasite based first generation vaccines, second generation vaccines
      based on antigenic protein or recombinant protein, and third generation vaccines
      derived from antigen-encoding DNA plasmids including heterologous prime-boost
      Leishmania vaccine have been examined for control and prevention of visceral
      leishmaniasis. Vaccines based on recombinant protein and antigen-encoding DNA
      plasmids have given promising results and few vaccines including Leishmune(r),
      Leishtec, and CaniLeish(r) have been licensed for canine visceral leishmaniasis.
      A systematic investigation of these vaccine candidates can lead to development of
      promising vaccine for human visceral leishmaniasis, most probably in the near
      future. 

PMID- 25858231
TI  - Lack of dissemination of acquired resistance to beta-lactams in small wild
      mammals around an isolated village in the Amazonian forest.
AB  - In this study, we quantitatively evaluated the spread of resistance to beta
      lactams and of integrons in small rodents and marsupials living at various
      distances from a point of antibiotic's use. Rectal swabs from 114 animals were
      collected in Trois-Sauts, an isolated village in French Guiana, and along a 3 km
      transect heading through the non-anthropized primary forest. Prevalence of
      ticarcillin-resistant enterobacteria was 36% (41/114). Klebsiella spp., naturally
      resistant to ticarcillin, were found in 31.1% (23/73) of animals from the village
      and in an equal ratio of 31.7% (13/41) of animals trapped along the transect. By
      contrast Escherichia coli with acquired resistance to ticarcillin were found in
      13.7% (10/73) of animals from the village and in only 2.4% (1/41) of those from
      the transect (600 m from the village). There was a huge diversity of E. coli and
      Klebsiella pneumoniae strains with very unique and infrequent sequence types. The
      overall prevalence of class 1 integrons carriage was 19.3% (22/114) homogenously
      distributed between animals from the village and the transect, which suggests a
      co-selection by a non-antibiotic environmental factor. Our results indicate that
      the anthropogenic acquired antibiotic resistance did not disseminate in the wild
      far from the point of selective pressure.

PMID- 25858233
TI  - A Pain in the Neck. Clay shoveler's fracture due to cervical spine trauma.

PMID- 25858234
TI  - It is time to attack pneumonia head-on.

PMID- 25858232
TI  - Alcohol misuse, genetics, and major bleeding among warfarin therapy patients in a
      community setting.
AB  - PURPOSE: Little is known about the impact of alcohol consumption on warfarin
      safety, or whether demographic, clinical, or genetic factors modify risk of
      adverse events. We conducted a case-control study to assess the association
      between screening positive for moderate/severe alcohol misuse and the risk of
      major bleeding in a community sample of patients using warfarin. METHODS: The
      study sample consisted of 570 adult patients continuously enrolled in Group Heath
      for at least 2 years and receiving warfarin. The main outcome was major bleeding
      validated through medical record review. Cases experienced major bleeding, and
      controls did not experience major bleeding. Exposures were Alcohol Use Disorders
      Identification Test Consumption Questionnaire (AUDIT-C) scores and report of
      heavy episodic drinking (>=5 drinks on an occasion). The odds of major bleeding
      were estimated with multivariate logistic regression models. The overall sample
      was 55% male, 94% Caucasian, and had a mean age of 70 years. RESULTS: Among 265
      cases and 305 controls, AUDIT-C scores indicative of moderate/severe alcohol
      misuse and heavy episodic drinking were associated with increased risk of major
      bleeding (OR = 2.10, 95% CI = 1.08-4.07; and OR = 2.36, 95% CI = 1.24-4.50,
      respectively). Stratified analyses demonstrated increased alcohol-related major
      bleeding risk in patients on warfarin for >=1 year and in those with a low-dose
      genotype (CYP2C9*2/*3, VKORC1(1173G>A), CYP4F2*1), but not in other sub-groups
      evaluated. CONCLUSIONS: Alcohol screening questionnaires, potentially coupled
      with genetic testing, could have clinical utility in selecting patients for
      warfarin therapy, as well as refining dosing and monitoring practices.

PMID- 25858235
TI  - Bundled Payment and Care of Acute Stroke: What Does it Take to Make it Work?

PMID- 25858236
TI  - Hemorrhage rates from brain arteriovenous malformation in patients with
      hereditary hemorrhagic telangiectasia.
AB  - BACKGROUND AND PURPOSE: Hereditary hemorrhagic telangiectasia (HHT) is a systemic
      disease characterized by mucocutaneous telangiectasias, epistaxis, and
      arteriovenous malformations (AVMs). Intracranial hemorrhage (ICH) rates in this
      population are not well described. We report ICH rates and characteristics in HHT
      patients with brain AVMs (HHT-BAVMs). METHODS: We studied the first 153 HHT-BAVM
      patients with follow-up data enrolled in the Brain Vascular Malformation
      Consortium HHT Project. We estimated ICH rates after BAVM diagnosis. RESULTS: The
      majority of patients were women (58%) and white (98%). The mean age at BAVM
      diagnosis was 31+/-19 years (range, 0-70), with 61% of cases diagnosed on
      asymptomatic screening. Overall, 14% presented with ICH; among symptomatic cases,
      37% presented ruptured. During 493 patient-years of follow-up, 5 ICH events
      occurred yielding a rate of 1.02% per year (95% confidence interval, 0.42-2.44%).
      ICH-free survival differed significantly by ICH presentation (P=0.003); ruptured
      cases had a higher ICH rate (10.07%; 95% confidence interval, 3.25-31.21%) than
      unruptured cases (0.43%; 95% confidence interval, 0.11-1.73%). CONCLUSIONS:
      Patients with HHT-BAVM who present with hemorrhage are at a higher risk for
      rehemorrhage compared with patients with BAVM detected presymptomatically.

PMID- 25858237
TI  - Relative distributions: a novel method for examining trends between stroke onset
      and thrombolysis time.
AB  - BACKGROUND AND PURPOSE: Analyses of trends in the delivery of time critical
      treatments typically report the median, but measures of central tendency may
      ignore important changes for specific patient groups. We considered whether this
      was an important effect during comparison of onset to treatment (OTT) time
      between 2 cohorts of patients with stroke receiving intravenous thrombolysis.
      METHODS: After controlling for stroke severity, a relative distributions
      technique compared OTT for UK patients treated with recombinant tissue-type
      plasminogen activator registered within the first and last quarters (each n=661)
      of the Safe Implementation of Thrombolysis in Stroke-Monitoring Study database
      between January 2003 and September 2010. RESULTS: Significant differences were
      found between OTT distributions. Overall, the second cohort's OTT distribution
      demonstrated simultaneous increases in the proportion of patients with faster and
      slower OTT, which resulted in no net effect on the median after correction for
      stroke severity. CONCLUSIONS: Medians did not adequately describe distributional
      changes. Faster OTT may be because of more efficient processes in acute stroke
      centers and improved symptom recognition by the public. Slower OTT is likely to
      reflect movement from a 3- to a 4.5-hour OTT target. Relative distributions offer
      new insights into historical trends and service evaluation where time critical
      treatments are involved.

PMID- 25858238
TI  - How is pneumonia diagnosed in clinical stroke research? A systematic review and
      meta-analysis.
AB  - BACKGROUND AND PURPOSE: Diagnosis of pneumonia complicating stroke is
      challenging, and there are currently no consensus diagnostic criteria. As a first
      step in developing such consensus-based diagnostic criteria, we undertook a
      systematic review to identify the existing diagnostic approaches to pneumonia in
      recent clinical stroke research to establish the variation in diagnosis and
      terminology. METHODS: Studies of ischemic stroke, intracerebral hemorrhage, or
      both, which reported occurrence of pneumonia from January 2009 to March 2014,
      were considered and independently screened for inclusion by 2 reviewers after
      multiple searches using electronic databases. The primary analysis was to
      identify existing diagnostic approaches for pneumonia. Secondary analyses
      explored potential reasons for any heterogeneity where standard criteria for
      pneumonia had been applied. RESULTS: Sixty-four studies (56% ischemic stroke, 6%
      intracerebral hemorrhage, 38% both) of 639 953 patients were included. Six
      studies (9%) reported no information on the diagnostic approach, whereas 12 (19%)
      used unspecified clinician-reported diagnosis or initiation of antibiotics. The
      majority used objective diagnostic criteria: 20 studies (31%) used respiratory or
      other published standard criteria; 26 studies (41%) used previously unpublished
      ad hoc criteria. The overall occurrence of pneumonia was 14.3% (95% confidence
      interval 13.2%-15.4%; I(2)=98.9%). Occurrence was highest in studies applying
      standard criteria (19.1%; 95% confidence interval 15.1%-23.4%; I(2)=98.5%). The
      substantial heterogeneity observed was not explained by stratifying for other
      potential confounders. CONCLUSIONS: We found considerable variation in
      terminology and the diagnostic approach to pneumonia. Our review supports the
      need for consensus development of operational diagnostic criteria for pneumonia
      complicating stroke.

PMID- 25858239
TI  - Twelve-Month Clinical and Quality-of-Life Outcomes in the Interventional
      Management of Stroke III Trial.
AB  - BACKGROUND AND PURPOSE: Randomized trials have indicated a benefit for
      endovascular therapy in appropriately selected stroke patients at 3 months, but
      data regarding outcomes at 12 months are currently lacking. METHODS: We compared
      functional and quality-of-life outcomes at 12 months overall and by stroke
      severity in stroke patients treated with intravenous tissue-type plasminogen
      activator followed by endovascular treatment as compared with intravenous tissue
      type plasminogen activator alone in the Interventional Management of Stroke III
      Trial. The key outcome measures were a modified Rankin Scale score <=2
      (functional independence) and the Euro-QoL EQ-5D, a health-related quality-of
      life measure. RESULTS: 656 subjects with moderate-to-severe stroke (National
      Institutes of Health Stroke Scale >=8) were enrolled at 58 centers in the United
      States (41 sites), Canada (7), Australia (4), and Europe (6). There was an
      interaction between treatment group and stroke severity in the repeated measures
      analysis of modified Rankin Scale <=2 outcome (P=0.039). In the 204 participants
      with severe stroke (National Institutes of Health Stroke Scale >=20), a greater
      proportion of the endovascular group had a modified Rankin Scale <=2 (32.5%) at
      12 months as compared with the intravenous tissue-type plasminogen activator
      group (18.6%, P=0.037); no difference was seen for the 452 participants with
      moderately severe strokes (55.6% versus 57.7%). In participants with severe
      stroke, the endovascular group had 35.2 (95% confidence interval: 2.1, 73.3) more
      quality-adjusted-days over 12 months as compared with intravenous tissue-type
      plasminogen activator alone. CONCLUSIONS: Endovascular therapy improves
      functional outcome and health-related quality-of-life at 12 months after severe
      ischemic stroke. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov.
      Unique identifier: NCT00359424.

PMID- 25858240
TI  - Cytological evaluation of spermatogenesis: a novel and simple diagnostic method
      to assess spermatogenesis in non-obstructive azoospermia using testicular sperm
      extraction specimens.
AB  - Most of the non-obstructive azoospermia (NOA)-patients have only focal
      spermatogenesis which results in insufficient numbers of spermatozoa to reach the
      ejaculate. In ~50% of these NOA-patients testicular sperm extraction (TESE) is
      successful and intracytoplasmic sperm injection (ICSI) is pursued. We studied
      whether (i) spermatogenesis can be evaluated by defining the ratios between
      Sertoli cells, pachytene spermatocytes and spermatozoa in a testicular cell
      suspension, and (ii) these ratios are associated with the outcome of fertility
      treatment. A retrospective cohort study was conducted between June 2007 and
      August 2012. In this period, 441 consecutive ICSI-TESE cycles were performed in
      212 couples. For each TESE biopsy, the ratios between Sertoli cells, pachytene
      spermatocytes and spermatozoa were calculated. A control population of 32
      vasectomized men was used to define cut-off values for complete spermatogenesis.
      Based on the pachytene to sperm ratio (P/Sp) and number of spermatozoa per 100
      Sertoli cells (#Sp/100SC) groups were defined as complete spermatogenesis,
      hypospermatogenesis and partial maturation arrest (MA). Validation of the
      cytological diagnoses was performed by comparing the results of cytology to the
      histological evaluation of spermatogenesis in 40 cases. In 92.5%, a perfect match
      was observed and in the three remaining cases cytology corresponded well with the
      results of TESE. Couples with complete spermatogenesis have a higher ongoing
      pregnancy rate after the first treatment cycle compared to couples with
      hypospermatogenesis (34 vs. 16%; p = 0.02) and partial MA (34 vs. 19%; p = 0.11).
      In conclusion, pachytene spermatocytes, spermatozoa and Sertoli cells can be
      easily identified and counted in a cell suspension and their ratios can be
      successfully used to diagnose the level of spermatogenic impairment. This pilot
      study indicates that once successful spermatozoa retrieval is achieved, treatment
      outcome declines when spermatogenesis is impaired in NOA. The predictive value of
      cytological evaluation of spermatogenesis has to be established in a future
      prospective trial. 

PMID- 25858241
TI  - Phaeocystidibacter marisrubri sp. nov., a member of the family Cryomorphaceae
      isolated from Red Sea sediment.
AB  - Strain G18(T), a Gram-stain-negative, aerobic, rod-shaped, motile, non
      fermentative, yellow-pigmented bacterium, was isolated from Red Sea sediment.
      Phylogenetic analyses based on 16S rRNA gene sequences revealed that strain
      G18(T) was most closely related to Phaeocystidibacter luteus PG2S01(T) with 95.3%
      similarity. Growth of strain G18(T) occurred at 10-42  degrees C (optimum 28-37 
      degrees C), pH 5.0-9.0 (optimum pH 6.0-8.0) and in the presence of 0.5-10% NaCl
      (optimum 2-5%). The major fatty acids of strain G18(T) were iso-C15 : 0, summed
      feature 3 (C16 : 1omega7c and/or C16 : 1omega6c), iso-C15 : 1 G and iso-C17 : 0 3
      OH. The major polar lipids were phosphatidylethanolamine, unidentified
      aminolipids, phospholipids and other lipids. The predominant quinone was
      menaquinone 6 (MK-6). The G+C content of the genomic DNA from strain G18(T) was
      39.0 mol%. Based on the phylogenetic and phenotypic properties, strain G18(T)
      represents a novel species of the genus Phaeocystidibacter, for which the name
      Phaeocystidibacter marisrubri sp. nov. is proposed. The type strain is G18(T) ( =
      CGMCC 1.14954(T)= JCM 30614(T)).

PMID- 25858242
TI  - Mycobacterium franklinii sp. nov., a species closely related to members of the
      Mycobacterium chelonae-Mycobacterium abscessus group.
AB  - Two isolates from water, D16Q19 and D16R27, were shown to be highly similar in
      their 16S rRNA, 16S-23S internal transcribed spacer (ITS), hsp65 and rpoB gene
      sequences to 'Mycobacterium franklinii' DSM 45524, described in 2011 but with the
      name not validly published. They are all nonpigmented rapid growers and are
      related phenotypically and genetically to the Mycobacterium chelonae
      Mycobacterium abscessus group. Extensive characterization by phenotypic analysis,
      biochemical tests, drug susceptibility testing, PCR restriction enzyme analysis
      of the hsp65 gene and ITS, DNA sequencing of housekeeping genes and DNA-DNA
      hybridization demonstrated that 'M. franklinii' DSM 45524, D16Q19 and D16R27
      belong to a single species that is separated from other members of the M.
      chelonae-M. abscessus group. On the basis of these results we propose the formal
      recognition of Mycobacterium franklinii sp. nov. Strain DSM 45524(T) ( = ATCC BAA
      2149(T)) is the type strain.

PMID- 25858243
TI  - Tumebacillus algifaecis sp. nov., isolated from decomposing algal scum.
AB  - Bacterial strain THMBR28(T) was isolated from decomposing algal scum that was
      collected during an algal bloom in Taihu lake, China. Cells of strain THMBR28(T)
      were Gram-staining-positive, facultatively anaerobic and rod-shaped. Growth was
      observed at 20-45  degrees C (optimum, 30  degrees C), at pH 5.0-9.5 (optimum, pH
      6.5-7.5), and in the presence of 0-1.0% (w/v) NaCl (optimum, 0.5%). Strain
      THMBR28(T) contained MK-7 as the major menaquinone and iso-C15 : 0 as the major
      cellular fatty acid. The polar lipid profile contained phosphatidylglycerol,
      phosphatidylmonomethylethanolamine, phosphatidylethanolamine and six unidentified
      polar lipids. The diamino acid found in the cell-wall peptidoglycan was meso
      diaminopimelic acid. The DNA G+C content was 57.6 mol% (Tm). Phylogenetic
      analysis of 16S rRNA gene sequences showed that strain THMBR28(T) belonged to the
      genus Tumebacillus, most closely related to Tumebacillus ginsengisoli DSM
      18389(T) (95.0%) and Tumebacillus permanentifrigoris Eur1 9.5(T) (93.4%). Based
      on phylogenetic and phenotypic characterization, it is concluded that strain
      THMBR28(T) represents a novel species of the genus Tumebacillus, for which the
      name Tumebacillus algifaecis sp. nov. is proposed, with THMBR28(T) ( = CGMCC
      1.10949(T) = NBRC 108765(T)) as the type strain.

PMID- 25858244
TI  - Pullulanibacillus pueri sp. nov., isolated from Pu'er tea.
AB  - A novel Gram-stain-positive, aerobic, endospore-forming, rod-shaped bacterial
      strain YN3(T) was isolated from ripened Pu'er tea. Phylogenetic analysis of 16S
      rRNA gene sequences showed that the strain belonged to the family
      Sporolactobacillaceae and was closely related to Pullulanibacillus naganoensis
      DSM 10191(T) (95.8% 16S rRNA gene sequence similarity) and Pullulanibacillus
      uraniitolerans DSM 19429(T) (95.4%). Growth of the strain was observed at 20-50 
      degrees C (optimum 30-37  degrees C), at pH 4.0-8.0 (optimum pH 5.0-6.0). The
      strain had a cell-wall type A1gamma peptidoglycan with meso-diaminopimelic acid
      as the diagnostic diamino acid. The predominant menaquinone was menaquinone-7 (MK
      7). The major fatty acids were anteiso-C15:0, anteiso-C17:0 and C18:1omega7c. The
      DNA G+C content of strain YN3(T) was 38.7 mol%. Strain YN3(T) could be
      differentiated from recognized species of the genus Pullulanibacillus based on
      phenotypic characteristics, chemotaxonomic differences, phylogenetic analysis and
      DNA-DNA hybridization data. On the basis of polyphasic evidence from this study,
      Pullulanibacilluspueri sp. nov., is proposed, with strain YN3(T) ( = CGMCC
      1.12777(T ) = JCM 30075(T)) as the type strain.

PMID- 25858245
TI  - Streptobacillus felis sp. nov., isolated from a cat with pneumonia, and emended
      descriptions of the genus Streptobacillus and of Streptobacillus moniliformis.
AB  - A pleomorphic, Gram-stain-negative, rod-shaped, indole-, oxidase- and catalase
      negative, non-spore-forming, non-motile bacterium (strain 131000547(T)) was
      isolated from the lungs of a cat with pneumonia. On the basis of 16S rRNA gene
      sequence analyses the strain was assigned to the genus Streptobacillus with 97.6%
      sequence similarity to the type strain of Streptobacillus moniliformis and 94.6%
      to that of Streptobacillus hongkongensis. The clear differentiation of strain
      131000547(T) from Streptobacillus moniliformis and Streptobacillus hongkongensis
      was also supported by gyrB, groEL, and recA nucleotide and amino acid sequence
      analysis. DNA-DNA hybridization demonstrated <= 19.9% (reciprocal 28.7%) DNA-DNA
      relatedness between strain 131000547(T) and Streptobacillus moniliformis DSM
      12112(T). Physiological data confirmed the allocation of strain 131000547(T) to
      the family Leptotrichiaceae. Strain 131000547(T) has a unique profile of enzyme
      activities allowing differentiation from the most closely related species. Within
      the genus Streptobacillus, isolate 131000547(T) could also unambiguously be
      separated from Streptobacillus moniliformis and Streptobacillus hongkongensis by
      both matrix-assisted laser desorption ionization time-of-flight mass spectrometry
      and Fourier transform-infrared spectroscopy. On the basis of these data, a novel
      species of the genus Streptobacillus, Streptobacillus felis sp. nov., is proposed
      with the type strain 131000547(T) ( = DSM 29248(T) = CCUG 66203(T) = CCM
      8542(T)). Emended descriptions of the genus Streptobacillus and of
      Streptobacillus moniliformis are also given.

PMID- 25858246
TI  - Paenibacillus qingshengii sp. nov., isolated from a lead-zinc tailing.
AB  - A novel bacterial strain, S1-9(T), was isolated from a lead-zinc tailing in
      Nanjing, Jiangsu Province, China. Cells of strain S1-9(T) were Gram-stain
      negative, ellipsoidal endospore-forming, aerobic rods and motile by means of
      peritrichous flagella. On the basis of 16S rRNA gene sequence analysis, strain S1
      9(T) was shown to belong to the genus Paenibacillus and the closest phylogenetic
      relatives were Paenibacillus glucanolyticus DSM 5162(T) (96.8% similarity),
      Paenibacillus lautus NRRL NRS-666(T) (96.5%) and Paenibacillus lactis MB 1871(T)
      (95.4%). The predominant menaquinone was MK-7. The major cellular fatty acids
      were anteiso-C15:0 and iso-C16:0. The polar lipid profile contained
      phosphatidylglycerol, phosphatidylethanolamine, diphosphatidylglycerol, two
      unknown phospholipids and two unknown lipids. The total DNA G+C content of strain
      S1-9(T) was 49.9 mol%. Based on the low levels of DNA-DNA relatedness (ranging
      from 21.8 to 48.4%) to the type strains of the above species of the genus
      Paenibacillus and unique phenotypic characteristics, strain S1-9(T) is considered
      to represent a novel species of the genus Paenibacillus, for which the name
      Paenibacillus qingshengii sp. nov. is proposed. The type strain is S1-9(T) ( =
      CCTCC AB 2014290(T) = JCM 30613(T)).

PMID- 25858247
TI  - Arthrobacter endophyticus sp. nov., an endophytic actinobacterium isolated from
      root of Salsola affinis C. A. Mey.
AB  - A Gram-staining-positive, white-coloured, aerobic, non-motile, catalase-positive
      and oxidase-negative, endophytic actinobacterium, designated strain EGI
      6500322(T), was isolated from the surface-sterilized root of the halophyte
      Salsola affinis C. A. Mey collected from Urumqi, Xinjiang province, north-west
      China. Growth occurred at 5-35  degrees C (optimum 25-30  degrees C), at pH 5-10
      (optimum pH 7-8) and with 0-13% NaCl (w/v) (optimum 0-5%). The predominant
      menaquinone was MK-9 (93.1%). The major cellular fatty acids were anteiso-C15:0
      (49.5%) and iso-C15:0 (15.1%). The cell-wall peptidoglycan contained lysine,
      alanine and glutamic acid. The major polar lipids were diphosphatidylglycerol,
      phosphatidylglycerol, phosphatidylinositol, two unknown phospholipids and one
      unknown glycolipid. The DNA G+C content of strain EGI 6500322(T) was 62.0 mol%.
      Based on 16S rRNA gene sequence analysis, the nearest phylogenetic neighbours of
      strain EGI 6500322(T) were identified as Arthrobacter ardleyensis DSM 17432(T)
      (98.38%) and Arthrobacter bergerei DSM 16367(T (98.37%). The DNA-DNA relatedness
      between strain EGI 6500322(T) and Arthrobacter ardleyensis DSM 17432(T) and
      Arthrobacter bergerei DSM 16367(T) was 53.4 +/- 4.1% and 30.5 +/- 1.7%,
      respectively. On the basis of the phylogenetic analysis, chemotaxonomic data,
      physiological characteristics and DNA-DNA hybridization data, strain EGI
      6500322(T) should represent a novel species of the genus Arthrobacter, for which
      the name Arthrobacter endophyticus sp. nov. is proposed. The type strain is EGI
      6500322(T) ( =  CTC 29490(T) = JCM 30091(T)).

PMID- 25858248
TI  - Elizabethkingia endophytica sp. nov., isolated from Zea mays and emended
      description of Elizabethkingia anophelisKampfer et al. 2011.
AB  - A slightly yellow bacterial strain (JM-87(T)), isolated from the stem of healthy
      10 day-old sweet corn (Zea mays), was studied for its taxonomic allocation. The
      isolate revealed Gram-stain-negative, rod-shaped cells. A comparison of the 16S
      rRNA gene sequence of the isolate showed 99.1, 97.8, and 97.4% similarity to the
      16S rRNA gene sequences of the type strains of Elizabethkingia anophelis,
      Elizabethkingia meningoseptica and Elizabethkingia miricola, respectively. The
      fatty acid profile of strain JM-87(T) consisted mainly of the major fatty acids
      C15:0 iso, C17:0 iso 3-OH, and C15:0 iso 2-OH/C16:1omega7c/t. The quinone system
      of strain JM-87(T) contained, exclusively, menaquinone MK-6. The major polyamine
      was sym-homospermidine. The polar lipid profile consisted of the major lipid
      phosphatidylethanolamine plus several unidentified aminolipids and other
      unidentified lipids. DNA-DNA hybridization experiments with E. meningoseptica
      CCUG 214(T) ( = ATCC 13253(T)), E. miricola KCTC 12492(T) ( = GTC 862(T)) and E.
      anophelis R26(T) resulted in relatedness values of 17% (reciprocal 16%), 30%
      (reciprocal 19%), and 51% (reciprocal 54%), respectively. These DNA-DNA
      hybridization results, in addition to some differentiating biochemical
      properties, clearly indicate that strain JM-87(T) is a representative of a novel
      species, for which the name Elizabethkingia endophytica sp. nov. is proposed. The
      type strain is JM-87(T) ( = CIP 110885(T) = LMG 28604(T) = CCM 8570(T)).

PMID- 25858249
TI  - Chryseobacterium arachidiradicis sp. nov., isolated from the geocarposphere (soil
      around the peanut) of very immature peanuts (Arachis hypogaea).
AB  - A yellow-pigmented bacterial strain, 91A-612(T), isolated from the geocarposphere
      (soil around the peanut) of very immature peanuts (Arachis hypogaea) in Alabama,
      USA, was studied for its taxonomic position. Cells of the isolate were rod-shaped
      and stained Gram-negative. A comparison of the 16S rRNA gene sequence with the
      sequences of the type strains of the most closely related species showed that the
      strain belongs to the genus Chryseobacterium, showing the highest sequence
      similarities to the type strains of Chryseobacterium molle (98.4%), C. pallidum
      (98.3%) and C. hominis (97.8%). The 16S rRNA gene sequence similarities to the
      type strains of all other species of the genus Chryseobacterium were below 97.0%.
      The fatty acid profile of strain 91A-612(T) consisted of the major fatty acids
      iso-C15 : 0, summed feature 3 (iso-C15 : 0 2-OH/C16 : 1omega7c) and iso-C17 : 0 3
      OH. Major compounds in the polar lipid profile were phosphatidylethanolamine and
      several unidentified lipids, including two lipids that did not contain a sugar
      moiety, an amino group or a phosphate group (L3, L8), and an aminolipid (AL1).
      The quinone system was composed mainly of MK-6. The polyamine pattern contained
      sym-homospermidine as the major compound and moderate amounts of spermidine and
      spermine. DNA-DNA hybridizations between strain 91A-612(T) and the type strains
      of C. molle, C. pallidum and C. hominis resulted in relatedness values well below
      70%. These data and the differentiating biochemical and chemotaxonomic properties
      showed that isolate 91A-612(T) represents a novel species of the genus
      Chryseobacterium, for which we propose the name Chryseobacterium arachidiradicis
      sp. nov. (type strain 91A-612(T) = LMG 27814(T)= CCM 8490(T) = CIP 110647(T)).

PMID- 25858250
TI  - Alcanivorax gelatiniphagus sp. nov., a marine bacterium isolated from tidal flat
      sediments enriched with crude oil.
AB  - A Gram-reaction-negative, rod-shaped marine bacterium, designated MEBiC08158(T),
      was isolated from sediments collected from Taean County, Korea, near the Hebei
      Spirit tanker oil spill accident. 16S rRNA gene sequence analysis revealed that
      strain MEBiC08158(T) was closely related to Alcanivorax marinus R8-12(T) (99.5%
      similarity) but was distinguishable from other members of the genus Alcanivorax
      (93.7-97.1%). The DNA-DNA hybridization value between strain MEBiC08158(T) and A.
      marinus R8-12(T) was 58.4%. Growth of strain MEBiC08158(T) was observed at 15-43 
      degrees C (optimum 37-40  degrees C), at pH 6.0-9.5 (optimum pH 7.0-8.0) and with
      0.5-16% NaCl (optimum 1.5-3.0%). The dominant fatty acids were C16 : 0, C19 : 0
      cyclo omega8c, C12 : 0, C18 : 1omega7c, C12 : 0 3-OH and summed feature 3
      (comprising C15 : 0 2-OH and/or C16 : 1omega7c). Several phenotypic
      characteristics differentiate strain MEBiC08158(T) from phylogenetically close
      members of the genus Alcanivorax. Therefore, strain MEBiC08158(T) should be
      classified as representing a novel species of the genus Alcanivorax, for which
      the name Alcanivorax gelatiniphagus sp. nov. is proposed. The type strain is
      MEBiC08158(T) ( = KCCM 42990(T) = JCM 18425(T)).

PMID- 25858251
TI  - Flaviaesturariibacter amylovorans gen. nov., sp. nov., a starch-hydrolysing
      bacterium, isolated from estuarine water.
AB  - A novel bacterial strain, designated GCR0105(T), was isolated from a water sample
      of the Mangyung estuary enclosed by the Saemangeum Embankment, located in
      JEOLlabuk-do, South Korea. Cells of strain GCR0105(T) were Gram-stain-negative,
      non-motile and rod-shaped. Colonies of strain GCR0105(T) were pale yellow
      pigmented on R2A agar and nutrient agar media, and were able to grow at 15-30 
      degrees C (optimum 25  degrees C) and pH 6.5-8.5 (optimum pH 7.5). Phylogenetic
      analysis based on 16S rRNA gene sequences revealed that strain GCR0105(T) was
      related most closely to Flavisolibacter ginsengisoli Gsoil 643(T) (93.14%
      similarity). The polar lipid profile of strain GCR0105(T) comprised
      phosphatidylethanolamine, two unknown aminolipids, an unknown aminophospholipid
      and four unknown lipids. The DNA G+C content of strain GCR0105(T) was 42.9 mol%
      and the respiratory quinone was MK-7.On the basis of phenotypic, chemotaxonomic
      and phylogenetic properties, strain GCR0105(T) represents a novel species in a
      new genus within the family Chitinophagaceae, for which the name
      Flaviaesturariibacter amylovorans gen. nov., sp. nov. is proposed. The type
      strain of Flaviaesturariibacter amylovorans is GCR0105(T) ( = KACC 16454(T) = JCM
      17919(T)).

PMID- 25858252
TI  - Commentary to Adam Oliver's 'Incentivising improvements in health care delivery'.
AB  - The commentary discusses key issues for assessment of performance management
      within health care. It supports the ambition to develop more realistic
      understandings of performance management based on insights from behavioral
      economics as suggested by Adam Oliver. However, it also points to several
      pitfalls and potential risks to consider when doing so. The commentary concludes
      that this is a promising field, but further research is needed to support the
      development of policy instruments. 

PMID- 25858253
TI  - Atypical chemokine receptor 1 deficiency reduces atherogenesis in ApoE-knockout
      mice.
AB  - AIMS: Atypical chemokine receptor 1 (Ackr1; previously known as the Duffy antigen
      receptor for chemokines or Darc) is thought to regulate acute inflammatory
      responses in part by scavenging inflammatory CC and CXC chemokines; however,
      evidence for a role in chronic inflammation has been lacking. Here we
      investigated the role of Ackr1 in chronic inflammation, in particular in the
      setting of atherogenesis, using the apolipoprotein E-deficient (ApoE(-/-)) mouse
      model. METHODS AND RESULTS: Ackr1(-/-)ApoE(-/-) and Ackr1(+/+)ApoE(-/-)
      littermates were obtained by crossing ApoE(-/-) mice and Ackr1(-/-) mice on a
      C57BL/6J background. Ackr1 (+/+)ApoE(-/-)mice fed a Western diet up-regulated
      Ackr1 expression in the aorta and had markedly increased atherosclerotic lesion
      size compared with Ackr1(-/-)ApoE(-/-) mice. This difference was observed in both
      the whole aorta and the aortic root in both early and late stages of the model.
      Ackr1 deficiency did not affect serum cholesterol levels or macrophage, collagen
      or smooth muscle cell content in atherosclerotic plaques, but significantly
      reduced the expression of Ccl2 and Cxcl1 in the whole aorta of ApoE(-/-) mice. In
      addition, Ackr1 deficiency resulted in a modest decrease in T cell subset
      frequency and inflammatory mononuclear phagocyte content in aorta and blood in
      the model. CONCLUSIONS: Ackr1 deficiency appears to be protective in the ApoE
      knockout model of atherogenesis, but it is associated with only modest changes in
      cytokine and chemokine expression as well as T-cell subset frequency and
      inflammatory macrophage content.

PMID- 25858254
TI  - Identification of natural products as modulators of OATP2B1 using LC-MS/MS to
      quantify OATP-mediated uptake.
AB  - CONTEXT: Organic anion-transporting polypeptide 2B1 (OATP2B1) which is highly
      expressed in enterocytes and hepatocytes could be a key determinant for the
      intestinal absorption and hepatic uptake of its substrate drugs. Natural products
      are commonly used in traditional Chinese medicine, foods, and beverages.
      OBJECTIVE: The objective of this study is to determine the OATP2B1-mediated drug
      interactions that could occur between natural products and OATP2B1 substrate
      drugs. MATERIALS AND METHODS: Human OATP2B1 was transiently expressed in human
      embryonic kidney (HEK293) cells and characterized by immunofluorescence, Western
      blot, and uptake assay. Liquid chromatography-tandem mass spectrometry (LC-MS/MS)
      methods for detecting OATP2B1 substrates estrone-3-sulfate (E3S) and three
      statins had been developed and were employed to investigate the effects of 27
      frequently used natural products on the function of OATP2B1. Uptake of 5 MUM E3S
      and 1 MUM statins in the absence or presence of natural products was measured at
      37  degrees C for 2 min with empty vector- and OATP2B1-transfected HEK293 cells.
      The IC50 values of inhibitors for OATP2B1-mediated 5 MUM E3S uptake were
      determined. RESULTS: Our results showed that mulberrin, scutellarin, quercetin,
      and glycyrrhetinic acid were strong inhibitors of OATP2B1-mediate E3S uptake with
      IC50 values being 1.8, 2.0, 7.5, and 13.0 MUM, which were comparable with their
      plasma concentrations in clinical trials. They also inhibited OATP-mediated
      uptake of atorvastatin, fluvastatin, and rosuvastatin. These results indicated
      that clinically relevant drug interactions could occur between these natural
      compounds and OATP2B1 substrate drugs. DISCUSSION AND CONCLUSION: The information
      obtained from this study might be helpful to predict and to avoid potential
      OATP2B1-mediated drug interactions.

PMID- 25858256
TI  - Public involvement in research should be "second nature" by 2025, review
      concludes.

PMID- 25858255
TI  - The Philadelphia Neurodevelopmental Cohort: constructing a deep phenotyping
      collaborative.
AB  - BACKGROUND: An integrative multidisciplinary approach is required to elucidate
      the multiple factors that shape neurodevelopmental trajectories of mental
      disorders. The Philadelphia Neurodevelopmental Cohort (PNC), funded by the
      National Institute of Mental Health Grand Opportunity (GO) mechanism of the
      American Recovery and Reinvestment Act, was designed to characterize clinical and
      neurobehavioral phenotypes of genotyped youths. Data generated, which are
      recently available through the NIMH Database of Genotypes and Phenotypes (dbGaP),
      have garnered considerable interest. We provide an overview of PNC recruitment
      and clinical assessment methods to allow informed use and interpretation of the
      PNC resource by the scientific community. We also evaluate the structure of the
      assessment tools and their criterion validity. METHODS: Participants were
      recruited from a large pool of youths (n = 13,958) previously identified and
      genotyped at The Children's Hospital of Philadelphia. A comprehensive
      computerized tool for structured evaluation of psychopathology domains (GOASSESS)
      was constructed. We administered GOASSESS to all participants and used factor
      analysis to evaluate its structure. RESULTS: A total of 9,498 youths (aged 8-21;
      mean age = 14.2; European American = 55.8%; African American = 32.9%; Other =
      11.4%) were enrolled. Factor analysis revealed a strong general psychopathology
      factor, and specific 'anxious-misery', 'fear', and 'behavior' factors. The
      'behavior' factor had a small negative correlation (-0.21) with overall accuracy
      of neurocognitive performance, particularly in tests of executive and complex
      reasoning. Being female had a high association with the 'anxious-misery' and low
      association with the 'behavior' factors. The psychosis spectrum was also best
      characterized by a general factor and three specific factors: ideas about
      'special abilities/persecution,' 'unusual thoughts/perceptions', and
      'negative/disorganized' symptoms. CONCLUSIONS: The PNC assessment mechanism
      yielded psychopathology data with strong factorial validity in a large diverse
      community cohort of genotyped youths. Factor scores should be useful for
      dimensional integration with other modalities (neuroimaging, genomics). Thus, PNC
      public domain resources can advance understanding of complex inter-relationships
      among genes, cognition, brain, and behavior involved in neurodevelopment of
      common mental disorders.

PMID- 25858257
TI  - Precise quantitation of 136 urinary proteins by LC/MRM-MS using stable isotope
      labeled peptides as internal standards for biomarker discovery and/or
      verification studies.
AB  - Spurred on by the growing demand for panels of validated disease biomarkers,
      increasing efforts have focused on advancing qualitative and quantitative tools
      for more highly multiplexed and sensitive analyses of a multitude of analytes in
      various human biofluids. In quantitative proteomics, evolving strategies involve
      the use of the targeted multiple reaction monitoring (MRM) mode of mass
      spectrometry (MS) with stable isotope-labeled standards (SIS) used for internal
      normalization. Using that preferred approach with non-invasive urine samples, we
      have systematically advanced and rigorously assessed the methodology toward the
      precise quantitation of the largest, multiplexed panel of candidate protein
      biomarkers in human urine to date. The concentrations of the 136 proteins span >5
      orders of magnitude (from 8.6 MUg/mL to 25 pg/mL), with average CVs of 8.6% over
      process triplicate. Detailed here is our quantitative method, the analysis
      strategy, a feasibility application to prostate cancer samples, and a discussion
      of the utility of this method in translational studies.

PMID- 25858258
TI  - Biodynamic performance of hyaluronic acid versus synovial fluid of the knee in
      osteoarthritis.
AB  - Hyaluronic acid (HA), a natural biomaterial present in healthy joints but
      depleted in osteoarthritis (OA), has been employed clinically to provide
      symptomatic relief of joint pain. Joint movement combined with a reduced joint
      lubrication in osteoarthritic knees can result in increased wear and tear,
      chondrocyte apoptosis, and inflammation, leading to cascading cartilage
      deterioration. Therefore, development of an appropriate cartilage model that can
      be evaluated for its friction properties with potential lubricants in different
      conditions is necessary, which can closely resemble a mechanically induced OA
      cartilage. Additionally, a comparison of different models with and without
      endogenous lubricating surface zone proteins, such as PRG4 promotes a well
      rounded understanding of cartilage lubrication. In this study, we present our
      findings on the lubricating effects of HA on different articular cartilage model
      surfaces in comparison to synovial fluid, a physiological lubricating
      biomaterial. The mechanical testings data demonstrated that HA reduced average
      static and kinetic friction coefficient values of the cartilage samples by 75%
      and 70%, respectively. Furthermore, HA mimicked the friction characteristics of
      freshly harvested natural synovial fluid throughout all tested and modeled OA
      conditions with no statistically significant difference. These characteristics
      led us to exclusively identify HA as an effective boundary layer lubricant in the
      technology that we develop to treat OA (Singh et al., 2014). 

PMID- 25858259
TI  - The role of the uncinate process in sinusitis aetiology: isolated agenesis versus
      maxillary sinus hypoplasia.
AB  - OBJECTIVE: This study aimed to evaluate the clinical significance of maxillary
      sinus hypoplasia and isolated agenesis of the uncinate process in sinusitis
      aetiology. METHODS: Three patients with isolated agenesis of the uncinate process
      and 27 patients with 43 maxillary sinus hypoplasia variations were recruited. The
      frequencies of sinusitis episodes and radiological findings were compared between
      patient subgroups. RESULTS: In all, 23 type I maxillary sinus hypoplasia, 13 type
      II maxillary sinus hypoplasia and 7 type III maxillary sinus hypoplasia
      variations were detected. Patients with isolated agenesis of the uncinate process
      underwent antibiotic treatment an average of 7 times per year, whereas those with
      types I, II and III maxillary sinus hypoplasia were treated 1.57, 3.22, and 5.75
      times per year, respectively, over a 5-year period. The antibiotic treatment
      frequency for patients with isolated agenesis of the uncinate process was
      significantly higher than for those with types I and II maxillary sinus
      hypoplasia. CONCLUSION: Isolated agenesis of the uncinate process seems to play a
      stronger role than types I and II maxillary sinus hypoplasia in the
      pathophysiology of chronic sinusitis.

PMID- 25858260
TI  - Bibliometric assessment of the Latin-American contributions in dengue.
AB  - BACKGROUND: Despite efforts in prevention and control of dengue, it is still a
      public health problem in the region. There are estimations of 13 million people
      affected in the Americas, therefore, it is of outmost importance to research it.
      An assessment on the Latin- American contributions on dengue was done. METHODS:
      Bibliometric study at SCI (1980- 2013), MEDLINE/GOPUBMED (1802-2013), Scopus
      (1959-2013), SCIELO (2004-2013), LILACS (1980- 2013). Different study types,
      characterized by years, city/country of origin, journals and more productive
      authors, by country, cites and H index have been conducted. RESULTS: At SCI, 2598
      articles were retrieved (21% of the total). Brazil was found to be the highest
      contributor (31.2%), then Puerto Rico (12.9%) and Mexico (10.7%). At Scopus,
      there are 2646 articles (16.7% of the total), 31.2% Brazil, 11.1% Mexico, 9.3%
      Cuba; the region received 41881 citations, 25.4% from Brazil (H index=45), 14.4%
      Cuba (H index=35) and 12.88% Puerto Rico (H index=38); 9.1% in Brazil were from
      Fundacao Oswaldo Cruz; 1.6% of Mexico corresponded to Instituto Nacional de Salud
      Publica, 4.9% of Cuba are from Instituto de Medicina Tropical Pedro Kouri. At
      Medline, there are 2799 records (33.9% from Brazil). At SciELO there are 825
      records (46.6% Brazil). At LILACS, there are 1178 records (46.8% Brazil).
      CONCLUSIONS: Brazil is the best producer in the region. In Puerto Rico and
      Brazil, there observed the epidemiologic burden of the disease. Scientific
      production in bibliographical data bases, particularly regional, is low, as
      compared to the high impact of the disease of in urban zones of the region.

PMID- 25858261
TI  - Dengue Patients Treated with Doxycycline Showed Lower Mortality Associated to a
      Reduction in IL-6 and TNF Levels.
AB  - OBJECTIVE: To determine the effect of doxycycline treatment on cytokine levels,
      including tumor necrosis factor (TNF) and interleukin 6 (IL-6), and mortality in
      dengue patients at high risk of complication. METHODS: A group of dengue
      hemorrhagic fever patients (n=231) were randomized to receive either standard
      supportive care or supportive care in addition to oral doxycycline twice daily
      for 7 days. Dengue virus infection was confirmed by PCR using multiple primers.
      Serum samples were obtained at days 0, 3, 5 and 7 and tested for levels of TNF
      and IL-6. RESULTS: Doxycycline-treated group presented a 46% lower mortality than
      that observed in the untreated group (11.2% [13/116] vs 20.9% [24/115],
      respectively, p=0.05). Moreover, administration of doxycycline resulted in a
      significant (p<0.01) decrease in levels of TNF and IL-6 versus controls in the
      tests performed during follow-up (day 3, 5 and 7). Patients who died in both
      groups possessed significantly (p<0.01) higher levels of TNF and IL-6 compared to
      those who survived at all-time points. CONCLUSION: The above findings suggest
      that doxycycline can provide a clinical benefit to dengue patients at high risk
      of complications. This effect could be mediated by decreasing pro-inflammatory
      cytokine levels.

PMID- 25858262
TI  - Bibliometric assessment of the contributions of literature on Chagas disease in
      Latin America and the Caribbean.
AB  - Chagas disease, considered a parasitic neglected disease, is endemic in Latin
      America. Although, its mortality rate has decreased over time, it still
      represents a public health problem in the region. A bibliometric evaluation of
      the Latin American contributions on this disease was done. This study used SCI
      (1980-2013), MEDLINE/GOPUBMED (1802-2013), Scopus (1959-2013), SCIELO (2004
      2013), and LILACS (1980-2013). Different study types have been characterized by
      years, origin city/country, journals and most productive authors, by country,
      cites and H-index. 2988 articles were retrieved from SCI (30.85% of total).
      Brazil was found to be the highest producer (31.22%), followed by Argentina
      (18.14%) and Mexico (9.57%); the region received 47241 citations, 28.60% for
      Brazil (H-index=52), 18.26% of Argentina (Hindex= 43), 11.40% Bolivia (H
      index=37). 4484 were retrieved from Scopus (30.20% of the total), 38.58% of which
      were from Brazil, 12.40% from Argentina and 8.90% from Mexico. From Medline, 6647
      records were retrieved (45.58% Brazil). From SciELO, 917 articles (47.66%
      Brazil). From LILACS, 2165 articles (60.05% Brazil). Brazil has the highest
      output in the region. Despite advances in controlling Chagas disease, scientific
      production is low, particularly for regional bibliographic databases, which calls
      for more research on this disease. 

PMID- 25858263
TI  - Does the mortality risk of social isolation depend upon socioeconomic factors?
AB  - This study considers whether socioeconomic status influences the impact of social
      isolation on mortality risk. Using data from the Alameda County Study, Cox
      proportional hazard models indicate that having a high income worsens the
      mortality risk of social isolation. Education may offset risk, however, and the
      specific pattern that emerges depends on which measures for socioeconomic status
      and social isolation are included. Additionally, lonely people who earn high
      incomes suffer especially high risk of accidents and suicides as well as cancer.
      Further research is needed that contextualizes the health risks of social
      isolation within the broader social environment.

PMID- 25858264
TI  - An assessment of WISC-IIIUK on children with HIV infection.
AB  - The Wechsler Intelligence Scale for Children - Third Edition UK test was
      administered to groups of children between the ages of 6 and 12 years with
      vertically transmitted HIV infection (n = 70) and a control group who were not
      infected by the virus (n = 70). The study was conducted in India. The two groups
      were matched for general verbal abilities, age and gender. The children were
      assessed for Verbal IQ, Performance IQ and Full-Scale IQ. The Verbal
      Comprehension Index, Perceptual Organization Index and Freedom from
      Distractibility Index were also obtained. A three-factor analysis of variance
      disclosed that school-age children with vertically transmitted HIV infection
      notched below in the areas of Verbal IQ, Performance IQ, Full-Scale IQ, Verbal
      Comprehension Index, Perceptual Organization Index and Freedom from
      Distractibility Index when collated with normal uninfected cohorts. Findings are
      discussed in the light of both theoretical and clinical implications.

PMID- 25858266
TI  - An unusual triad of pneumatosis intestinalis, portal venous gas and
      pneumoperitoneum in an asymptomatic patient.
AB  - Pneumatosis intestinalis (PI) is defined as the presence of gas within the
      serosal or mucosal layer bowel wall. This sign is usually found upon radiographic
      imaging and is most commonly secondary to acute gastro-intestinal ischaemia.
      Fifteen per cent of cases can present with a primary condition called pneumatosis
      cystoides intestinalis (PCI). PCI is usually a benign condition and patients are
      usually asymptomatic. Portal venous gas (PVG) or the presence/accumulation of
      free gas within the hepatic portal vein. It is most commonly associated with
      acute bowel ischaemia, and when seen in the presence of ischaemia the mortality
      rate is between 75 and 90%. Other associations include mechanical causes (e.g.
      obstruction), chemotherapy, liver transplant and diverticulitis. Benign PI has
      previously been described with PVG, but usually in the presence of other
      associated conditions such as AIDS, malignancy or chemotherapy. Some examples
      have been described without these associations, but not with free intra
      peritoneal air. We describe a case of PCI and PVG with pneumoperitoneum,
      investigations and ongoing management. 

PMID- 25858265
TI  - Disease activity guided dose reduction and withdrawal of adalimumab or etanercept
      compared with usual care in rheumatoid arthritis: open label, randomised
      controlled, non-inferiority trial.
AB  - OBJECTIVE: To evaluate whether a disease activity guided strategy of dose
      reduction of two tumour necrosis factor (TNF) inhibitors, adalimumab or
      etanercept, is non-inferior in maintaining disease control in patients with
      rheumatoid arthritis compared with usual care. DESIGN: Randomised controlled,
      open label, non-inferiority strategy trial. SETTING: Two rheumatology outpatient
      clinics in the Netherlands, from December 2011 to May 2014. PARTICIPANTS: 180
      patients with rheumatoid arthritis and low disease activity using adalimumab or
      etanercept; 121 allocated to the dose reduction strategy, 59 to usual care.
      INTERVENTIONS: Disease activity guided dose reduction (advice to stepwise
      increase the injection interval every three months, until flare of disease
      activity or discontinuation) or usual care (no dose reduction advice). Flare was
      defined as increase in DAS28-CRP (a composite score measuring disease activity)
      greater than 1.2, or increase greater than 0.6 and current score of at least 3.2.
      In the case of flare, TNF inhibitor use was restarted or escalated. MAIN OUTCOME
      MEASURES: Difference in proportions of patients with major flare (DAS28-CRP based
      flare longer than three months) between the two groups at 18 months, compared
      against a non-inferiority margin of 20%. Secondary outcomes included TNF
      inhibitor use at study end, functioning, quality of life, radiographic
      progression, and adverse events. RESULTS: Dose reduction of adalimumab or
      etanercept was non-inferior to usual care (proportion of patients with major
      flare at 18 months, 12% v 10%; difference 2%, 95% confidence interval -12% to
      12%). In the dose reduction group, TNF inhibitor use could successfully be
      stopped in 20% (95% confidence interval 13% to 28%), the injection interval
      successfully increased in 43% (34% to 53%), but no dose reduction was possible in
      37% (28% to 46%). Functional status, quality of life, relevant radiographic
      progression, and adverse events did not differ between the groups, although short
      lived flares (73% v 27%) and minimal radiographic progression (32% v 15%) were
      more frequent in dose reduction than usual care. CONCLUSIONS: A disease activity
      guided, dose reduction strategy of adalimumab or etanercept to treat rheumatoid
      arthritis is non-inferior to usual care with regard to major flaring, while
      resulting in the successful dose reduction or stopping in two thirds of
      patients.Trial registration Dutch trial register (www.trialregister.nl), NTR
      3216.

PMID- 25858267
TI  - Tumoral calcinosis of the hand.
AB  - Tumoral calcinosis is a rare condition described in literature as a deposition of
      calcium salts in soft tissues. We here report a rare case of Tumoral calcinosis
      in the index finger of a hand in a 22-year-old woman. Because of the absence of
      any trauma, normal serum phosphate and calcium levels and no symptoms but a
      cosmetic defect, our case is classified as a primary tumoral calcinosis. As well
      as described in literature, also in this case the surgical excision was the
      mainstay treatment for this benign pathology. For the particular area involved we
      performed a radical excision followed by an interesting reverse homodigital
      artery flap from the ulnar side of the index. 

PMID- 25858268
TI  - Excess anticoagulation as a cause of small-bowel obstruction: a report of two
      cases.
AB  - Spontaneous intramural haemorrhage is a rare cause of small-bowel obstruction,
      occurring most commonly in those who are anticoagulated. We describe two cases
      that presented with a history and imaging suggestive of small-bowel obstruction;
      both had International Normalized Ratios of above 10 on admission. The first
      case, a 62-year-old lady on warfarin for atrial fibrillation, was managed
      conservatively with good effect. In contrast, the second case, a 57-year-old
      gentleman on warfarin for his metallic aortic valve, underwent diagnostic
      laparotomy that revealed a 30-cm segment of proximal jejunum with spontaneous
      intramural haemorrhage. In this study, we emphasize the merit of conservative
      management for this rare cause of small-bowel obstruction. 

PMID- 25858269
TI  - Scientific research in malaria: bibliometric assessment of the Latin-American
      contributions.
AB  - BACKGROUND: Malaria is a parasitic disease of high global impact in public
      health, including Latin America. There should be more researched, particularly in
      this region. A bibliometric assessment of the Latin American contributions about
      malaria was done. METHODS: Bibliometric study at SCI (1980-2013), MEDLINE/
      GOPUBMED (1802-2013), Scopus (1959-2013), SCIELO (2004-2013), LILACS (1980-2013).
      The studies were characterized by study type, year of publication, city/country
      of origin, journals and more productive authors, citations and H index. RESULTS:
      At SCI, 2,806 articles were retrieved (5.13% of the total). Brazil was the
      highest producer (31.41%), followed by Colombia (14.3%) and Mexico (9.5%). The
      region received 39,894 citations, 32.2% from Brazil (H index=51), 12.75% Mexico
      (H index=38), 11.2% Colombia (H index=33). At Scopus, there are 4,150 articles
      (4.9% of the total), 33.0% Brazil, 11.3% Colombia and 8.8% Mexico; 17% in Brazil
      were from Universidad de Sao Paulo; 23.6% of Colombia from Universidad de
      Antioquia; 15.4% of Mexico from Instituto Nacional de Salud Publica. At Medline
      there were 4,278 records (36.8% Brazil). At SciELO there are 792 records (45.3%
      Brazil). At LILACS there were 1744 records (34.3% Brazil). CONCLUSIONS: Brazil
      has the highest output of the region, as Venezuela the scientific production in
      Malaria was related with the burden of disease. This was not the case for
      Colombia. Scientific production at bibliographical databases, particularly
      regionals, is low, compared to the high incidence of this disease that requires
      more research and control.

PMID- 25858270
TI  - Study of the scientific production on leishmaniasis in Latin America.
AB  - Leishmaniasis is a highly relevant neglected tropical disease. It has important
      consequences in affected populations, including a high fatality rate in its
      visceral form. It is present in Latin America, then it is necessary to promote
      more research on it. A bibliometric assessment of the Latin American scientific
      production in leishmaniasis was done. METHODS: Bibliometric study at SCI (1980
      2013), MEDLINE/GOPUBMED (1802-2013), Scopus (1959-2013), SCIELO (2004-2013),
      LILACS (1980-2013). Different study types, characterized by years, city/country
      of origin, journals and more productive authors, by country, cites and H index.
      RESULTS: At SCI, 2857 articles were found (17.7% of the total). Brazil was the
      highest producer (58.1%), followed by Colombia (9.9%) and Venezuela (5.6%); the
      region received 41186 citations, 54.2% of Brazil (H index=62), 12.1% Colombia (H
      index=30) and 4.5% of Venezuela (H index=25). At Scopus, there are 3681 (14.7% of
      the total), 53.2% Brazil, 6.8% Colombia and 6.0% Venezuela; 38.46% at Brazil were
      from Fundacao Oswaldo Cruz; 30.6% of Colombia corresponded to Universidad de
      Antioquia; 31.34% at Venezuela were from Universidad Central de Venezuela. At
      Medline there are 4525 records (60.6% of Brazil). At SciELO there are 1068
      records (67.5% Brazil). At LILACS, there are 1740 records (56.0% Brazil).
      CONCLUSIONS: Scientific production of Brazil predominates in the region, with one
      single institution generating more articles than Colombia and Venezuela together.
      Scientific production in bibliographical data bases, particularly regional, is
      still relatively low, and the disease neglected when compared to other tropical
      conditions such as dengue and malaria.

PMID- 25858271
TI  - Polymorphic differences in the SOD-2 gene may affect the pathogenesis of
      nephropathy in patients with diabetes and diabetic complications.
AB  - The effective treatment of diabetes and the prevention of diabetic complications
      may be improved by a better understanding of the antioxidant function of
      intracellular defences against oxidative stress. Polymorphisms in antioxidant
      genes may determine cellular oxidative stress levels as a primary pathogenic role
      in diabetes and/or in its complications. SOD-2 was investigated in patients with
      type 1 diabetes mellitus (T1DM) to ascertain if specific genotypes have any
      protective influences in the pathogenic mechanisms in diabetes and/or in several
      different complications, including retinopathy, nephropathy and diabetic controls
      compared to normal healthy controls. METHOD: 278 (136M:142F) T1DM patients and
      135 (72M:63F) normal, healthy controls were investigated for SOD-2 polymorphism
      in the mitochondrial targeting sequence with Ala/Val (C-9T) substitution.
      RESULTS: A significant difference in the C-9-T genotype was observed between
      patients and normal controls but not between diabetic controls and patients with
      complications. There were significantly more of the diabetic control (DC, n=62)
      group (11.3%) than the patients with diabetic nephropathy (DN, n=73) (1.4%) with
      the CC genotype (p=0.03 and chi(2)=4.27, OR=9.16 (1.08<OR<204.03)). Further
      significance was found between normal healthy controls (11.4%) and patients with
      nephropathy (1.4%) with the genotype CC (p=0.03, chi(2)=4.68, OR=0.11
      (0.00<OR<0.87)). No significant differences were found between these groups for
      the allelic frequency or between the different complication groups after
      correction for the number of groups. All groups were in Hardy Weinberg
      equilibrium. CONCLUSION: The SNP in SOD-2 results in a substitution of C to T,
      which causes an amino acid change from alanine to valine. The variation in the
      SOD-2 leader signal affects the processing efficiency of the enzyme. A
      significantly greater proportion of the diabetic control group had the CC
      genotype suggesting antioxidant protection against diabetic nephropathy. The
      healthy control group also had a higher incidence of the protective genotype,
      which may suggest protective influences from the antioxidant gene in the CC form.

PMID- 25858273
TI  - Two-component phosphorelays in fungal mitochondria and beyond.
AB  - Prokaryotes, eukaryotic microorganisms and plants utilize two-component signal
      transduction pathways to detect and respond to various environmental cues. These
      signaling cascades were acquired by eukaryotes via horizontal gene transfer
      events from ancestral bacteria. Recent exciting discoveries have identified two
      component signaling systems in mitochondria and chloroplasts of several
      eukaryotic microorganisms and plants, therefore providing important clues to the
      evolutionary transition of these signaling cascades from prokaryotes to
      eukaryotes. This review will focus on the role of two-component signal
      transduction pathways in fungal pathogenesis and also discuss key new discoveries
      of presence of proteins participating in these signaling pathways in
      mitochondrion. Before addressing these issues, I first briefly describe the
      magnitude and the economic impact of the healthcare problems caused by fungal
      pathogens. 

PMID- 25858274
TI  - Neutrino and cosmic-ray emission from multiple internal shocks in gamma-ray
      bursts.
AB  - Gamma-ray bursts (GRBs) are short-lived, luminous explosions at cosmological
      distances, thought to originate from relativistic jets launched at the deaths of
      massive stars. They are among the prime candidates to produce the observed cosmic
      rays at the highest energies. Recent neutrino data have, however, started to
      constrain this possibility in the simplest models with only one emission zone. In
      the classical theory of GRBs, it is expected that particles are accelerated at
      mildly relativistic shocks generated by the collisions of material ejected from a
      central engine. Here we consider neutrino and cosmic-ray emission from multiple
      emission regions since these internal collisions must occur at very different
      radii, from below the photosphere all the way out to the circumburst medium, as a
      consequence of the efficient dissipation of kinetic energy. We demonstrate that
      the different messengers originate from different collision radii, which means
      that multi-messenger observations open windows for revealing the evolving GRB
      outflows. 

PMID- 25858272
TI  - Cis- and trans-regulation of luteovirus gene expression by the 3' end of the
      viral genome.
AB  - Translation of the 5.7 kb luteovirus genome is controlled by the 3' untranslated
      region (UTR). Base pairing between regions of the 3' UTR and sequences kilobases
      upstream is required for cap-independent translation and ribosomal frameshifting
      needed to synthesize the viral replicase. Luteoviruses produce subgenomic RNAs,
      which can serve as mRNA, but one sgRNA also regulates translation initiation in
      trans. As on all viruses, the 3' and 5' ends contain structures that are presumed
      to facilitate RNA synthesis. This review describes the structures and
      interactions of barley yellow dwarf virus RNA that facilitate the complex
      interplay between the above events and result in a successful virus infection. We
      also present surprising results on the apparent lack of need for some subgenomic
      RNAs for the virus to infect cells or whole plants. In summary, the UTRs of
      luteoviruses are highly complex entities that control and fine-tune many key
      events of the virus replication cycle.

PMID- 25858275
TI  - Regional anesthesia alone for pediatric free flaps.
AB  - Microvascular surgery plays an important reconstructive role in the pediatric
      population. Successful outcomes rely on surgical technique as well as anesthesia.
      Regional anesthesia contributes to successful free tissue transfer through
      sympathetic blockade, postoperative pain control, and elimination of risks and
      costs associated with general anesthesia. While regional anesthesia in
      microsurgery is discussed in the literature for adult and elderly patients, no
      studies focus on the pediatric population. Accordingly, this paper reviews 20
      pediatric patients undergoing microvascular surgery (anterolateral thigh, n = 9;
      gracilis, n = 3; toe transfer, n = 6; and fibula, n = 2) with regional anesthesia
      and sedation. All patients underwent spinal epidural anesthesia, and seven also
      received brachial plexus blocks. The average duration of anesthesia was 3-4 h
      (anterolateral thigh (ALT) and gracilis) and 6-8 h (toe transfer and fibula). No
      anesthesia-related complications or flap failures occurred. We conclude that
      regional anesthesia has important benefits in pediatric microsurgery and it is a
      safe and cost-effective alternative to general anesthesia. 

PMID- 25858277
TI  - Pain and Personality: Do Individuals with Different Forms of Chronic Pain Exhibit
      a Mutual Personality?
AB  - The role of personality in the experience of chronic pain is a growing field,
      with endless debate regarding the existence of a "pain personality". This study
      aims to compare different chronic pain types and consolidate the existence of a
      common personality. Thirty-two females with chronic orofacial pain and 37 age
      matched healthy females were assessed with the Temperament and Character
      Inventory-Revised. Chronic pain subjects had either trigeminal neuropathy
      (neuropathic pain) or temporomandibular disorders (nociceptive pain). This study
      revealed that individuals with different chronic pain types exhibit a mutual
      personality profile encompassing significantly higher scores in Harm Avoidance
      and significantly lower scores in Self-Directedness when compared to healthy
      subjects. In fact, this combination is associated with Cluster C personality
      disorders. In conclusion, our study reveals that irrespective of type, chronic
      pain may be associated with Cluster C personality disorders. Indeed, there has
      never been empirical evidence in the past to suggest that chronic pain as an
      overall concept is associated with any particular personality disorders.
      Therefore, a potential future avenue of chronic pain treatment may lie in
      targeting particular personality aspects and shift the target of pain-relieving
      treatments from sensory and psychologically state focused to psychologically
      trait focused. 

PMID- 25858276
TI  - Replantation vs revision amputation in single digit zone II amputations.
AB  - The objective of this study was to compare the functional outcomes of zone II
      amputations treated with either replantation or revision amputation at our
      institution to better aid patients in their decision making process regarding
      these treatment options. We conducted a comparative retrospective study. All
      cases of single digit amputations received at our replantation center between
      2007 and 2011 were screened for single digit zone II injuries. These patients
      were stratified based on the treatment received: replantation vs revision
      amputation. Patients were called and invited to participate in the research
      project. Those who accepted to enter the study were asked to complete the Quick
      DASH, the Beck Depression Inventory-short form, and a custom made questionnaire.
      There were seventeen patients with single digit zone II replantation and fourteen
      patients with similar injuries who underwent revision amputation and agreed to
      take part in the study. Our data revealed that the duration of sick leave,
      occupation after injury, professional and social reintegration, discontinued
      activities, and self-confidence were not statistically different between the two
      groups. The average hospital stay and the follow-up period of replanted
      individuals were longer. The replantation group did not have higher levels of
      pain or cold intolerance, and the global functional and esthetic satisfaction
      levels were similar between the two groups. Also, Beck Depression Inventory and
      Quick-DASH scores were not statistically different. Yet, significantly more
      patients in the replantation group would opt to repeat the replantation than
      revised patients would opt for revision amputation. From a functional viewpoint,
      our study suggests that revision amputation is not superior to replantation in
      zone II single digit amputations. This is valuable information that should be
      given to patients when deciding on the treatment process and to insure a proper
      informed consent. 

PMID- 25858278
TI  - In-vitro antibacterial, antifungal, antioxidant and functional properties of
      Bacillus amyloliquefaciens.
AB  - BACKGROUND: Food born pathogenic bacteria and filamentous fungi are able to grow
      on most foods, including natural foods, processed foods, and fermented foods and
      create considerable economic loss. The aim of this study was to determine the
      antibacterial, antifungal, antioxidant and functional properties of Bacillus
      amyloliquefaciens recovered from silage. METHODS: Minimum Inhibitory
      Concentration (MIC) of the compounds was assessed by using broth micro dilution
      method. The 1,1-diphenyl-2-picrylhydrazyl (DPPH)-radical scavenging and hydroxyl
      radical-scavenging abilities were measured to evaluate antioxidant activity of
      the strain. RESULTS: Primary antimicrobial compound production screening revealed
      that B. amyloliquefaciens exhibited significant activity against all the tested
      bacteria and fungi compared to other strains. The 16S rRNA and gyrase A gene
      sequence analysis determined using molecular biological tools confirmed that the
      strain was 99% similarity towards B. amyloliquefaciens. The Minimum Inhibitory
      Concentration (MIC) of ethyl acetate extract against Bacillus subtilis,
      Enterococcus cloacae and Staphylococcus aureus were 25.0 MUg ml-1, and S,
      epidermidis were 12.5 MUg ml-1, respectively. Filamentous fungi Aspergillus
      clavatus, A. fumigates, A. niger and Gibberella moniliformis showed 25 MUg ml-1.
      VJ-1 was able to survive the gastrointestinal conditions simulating the stomach
      and duodenum passage with the highest percentage of hydrophobicity. In addition,
      its resistance to hydrogen peroxide and highest hydroxyl radical and 2, 2
      diphenyl-1-picrylhydrazyl (DPPH) scavenging activities, with inhibition rates of
      56.84% and 67.12% respectively, were its advantage. An antimicrobial
      susceptibility pattern was an intrinsic feature of this strain, and thus,
      consumption does not represent a health risk to humans. CONCLUSION: Bacillus
      amyloliquefaciens might be a promising candidate for new pharmaceutical agents
      and probiotics.

PMID- 25858279
TI  - Quality of life and its correlates in diabetic outpatients in Swaziland.
AB  - BACKGROUND: Diabetes is a chronic disease requiring frequent monitoring that may
      be accompanied by considerable quality of life (QOL) burden. Low- and middle
      income countries such as Swaziland are facing a double disease burden exacerbated
      by the high prevalence of infectious diseases. This study aimed to understand the
      QOL and its correlates in diabetic outpatients in Swaziland. METHODS:
      Participants were consecutively recruited during their routine visits to a
      referral hospital in Swaziland. Face-to-face interviews were conducted with
      outpatients using the Diabetes-39 questionnaire to measure their QOL. Raw scores
      were transformed to a standard domain-specific score using linear transformation
      with scores ranging from 0 (lowest impact) to 100 (highest impact). RESULTS:
      Among the 340 participants in this cross-sectional study anxiety and worry was
      the most affected QOL domain. In multiple linear regression analyses, the
      presence of complications and/or comorbidities, low income, limited education and
      being on insulin therapy, showed higher impacts of diabetes on the participants'
      QOL. CONCLUSIONS: The high impact of diabetes on anxiety and worry QOL score
      highlights the need to address diabetic patients' psychological wellbeing in the
      clinical management of diabetes. An integrated diabetes care program that takes
      into account the impacts of sociodemographic and clinical factors on QOL may
      improve the QOL of diabetic patients.

PMID- 25858280
TI  - Knowledge, attitude and preventive practices regarding dengue fever in rural
      areas of Yemen.
AB  - BACKGROUND: In recent years there have been several reports of outbreaks of
      dengue fever (DF) in Yemen. This study aimed to describe the prevailing
      knowledge, attitude and preventive practices regarding DF, and to investigate the
      factors associated with poor preventive practices in rural areas of Yemen.
      METHODS: A population-based, cross-sectional study was conducted on 804 randomly
      selected heads of household. A pretested, structured questionnaire was
      administered through face-to-face interviews. Logistic regression was used to
      investigate factors independently associated with poor practice. RESULTS: Out of
      804 participants, 753 (93.7%) were aware of the symptoms of DF and 671 (83.4%)
      knew that DF was transmitted by mosquito bites. Only 420 (52.2%) knew that direct
      person-to-person transmission was not possible. Furthermore, 205 (25.5%) thought
      that someone with DF should be avoided and 460 (57.2%) thought the elimination of
      breeding sites was the responsibility of health authorities. Poor knowledge of DF
      and a low level of education were significantly associated with poor preventive
      practices. CONCLUSIONS: In rural areas of Yemen, people have a vague
      understanding of DF transmission and a negative attitude towards preventative
      practices. Efforts should be made to correct misconceptions about transmission of
      the disease and to highlight the importance of community participation in control
      activities.

PMID- 25858281
TI  - Mail-Based Intervention for Sarcopenia Prevention Increased Anabolic Hormone and
      Skeletal Muscle Mass in Community-Dwelling Japanese Older Adults: The INE
      (Intervention by Nutrition and Exercise) Study.
AB  - OBJECTIVE: The aim of the Intervention by Nutrition and Exercise (INE) study was
      to investigate the effects of a mail-based intervention for sarcopenia prevention
      on muscle mass and anabolic hormones in community-dwelling older adults. DESIGN:
      A cluster-randomized controlled trial. SETTING AND PARTICIPANTS: This trial
      recruited community-dwelling adults aged 65 years and older in Japan. The 227
      participants were cluster randomized into a walking and nutrition (W/N) group (n
      = 79), a walking (W) group (n = 71), and a control (C) group (n = 77). We
      analyzed the physical and biochemical measurements in this substudy.
      INTERVENTION: Six months of mail-based intervention (a pedometer-based walking
      program and nutritional supplementation). MEASUREMENTS: The skeletal muscle mass
      index (SMI) using the bioelectrical impedance data acquisition system,
      biochemical measurements, such as those of insulinlike growth factor (IGF-1),
      dehydroepiandrosterone sulfate (DHEA-S), and 25-hydroxy vitamin D (25[OH]D), as
      well as frailty, were assessed by the Cardiovascular Health Study criteria.
      RESULTS: Participants in the W/N and W groups had significantly greater
      improvements in SMI, IGF-1, and 25(OH)D (P < .05) than those in the C group.
      Participants in the W/N group had significantly greater improvements in DHEA-S (P
      < .05) than in the other groups. These effects were more pronounced in frail,
      older adults. CONCLUSION: These results suggest that the mail-based walking
      intervention of the remote monitoring type for sarcopenia prevention can increase
      anabolic hormone levels and SMI in community-dwelling older adults, particularly
      in those who are frail.

PMID- 25858282
TI  - Toward a Comprehensive Model of Frailty: An Emerging Concept From the Hong Kong
      Centenarian Study.
AB  - OBJECTIVES: A better understanding of the essential components of frailty is
      important for future developments of management strategies. We aimed to assess
      the incremental validity of a Comprehensive Model of Frailty (CMF) over Frailty
      Index (FI) in predicting self-rated health and functional dependency amongst near
      centenarians and centenarians. DESIGN: Cross-sectional, community-based study.
      SETTING: Two community-based social and clinical networks. PARTICIPANTS: One
      hundred twenty-four community-dwelling Chinese near-centenarians and
      centenarians. MEASUREMENTS: Frailty was first assessed using a 32-item FI (FI
      32). Then, a new CMF was constructed by adding 12 items in the psychological,
      social/family, environmental, and economic domains to the FI-32. Hierarchical
      multiple regressions explored whether the new CMF provided significant additional
      predictive power for self-rated health and instrumental activities of daily
      living (IADL) dependency. RESULTS: Mean age was 97.7 (standard deviation 2.3)
      years, with a range from 95 to 108, and 74.2% were female. Overall, 16% of our
      participants were nonfrail, 59% were prefrail, and 25% were frail. Frailty
      according to FI-32 significantly predicted self-rated health and IADL dependency
      beyond the effect of age and gender. Inclusion of the new CMF into the regression
      models provided significant additional predictive power beyond FI-32 on self
      rated health, but not IADL dependency. CONCLUSIONS: A CMF should ideally be a
      multidimensional and multidisciplinary construct including physical, cognitive,
      functional, psychosocial/family, environmental, and economic factors.

PMID- 25858283
TI  - Physicians in nursing homes: effectiveness of physician accountability and
      communication.
AB  - OBJECTIVES: The objective of this study was to develop a measure of the
      perceptions of nursing home (NH) directors of nursing (DONs) on the adequacy of
      physician care and to examine its variation as well as its construct validity.
      DESIGN: A nationwide cross-sectional study with primary data collection. SETTING:
      A total of 2043 NHs surveyed between August 2009 and April 2011. PARTICIPANTS:
      DONs and NH administrators responded to questions pertaining to their perceptions
      of the care provided by physicians in their NH. MEASUREMENTS: Ten items were used
      to create 3 domains: medical staff attentiveness, physician communication, and
      staff concerns about physician practice. These were combined into an overall
      summary score measure called "Effectiveness of Physician Accountability and
      Communication" (EPAC). EPAC construct validity was ascertained from other DON
      questions and from a complementary survey of NH administrators. RESULTS: The
      established EPAC score is the first measure to capture specific components of the
      adequacy of physician care in NHs. EPAC exhibited good construct validity: more
      effective practices were correlated with greater physician involvement in
      discussions of do-not-resuscitate orders, the frequency with which the medical
      director checked on the medical care delivered by the attending physician, the
      tightness of the NH's control of its physician resources, and the DON's
      perception of whether or not avoidable hospitalizations and emergency room visits
      could be reduced with greater physician attention to resident needs. CONCLUSION:
      As increased attention is given to the quality of care provided to vulnerable
      elders, effective measures of processes of care are essential. The EPAC measure
      provides an important new metric that can be used in these efforts. The goal is
      that future studies could use EPAC and its individual domains to shed light on
      the manner through which physician presence is related to resident outcomes in
      the NH setting.

PMID- 25858284
TI  - Change in therapeutic apheresis practices: Role of continuing medical education
      (CME).
AB  - INTRODUCTION: American society for apheresis (ASFA) publishes guidelines for
      therapeutic apheresis (TA) and physicians ordering TA procedures should be aware
      of the appropriate indications based on scientific evidence. Transfusion Medicine
      specialists (apheresis physicians) can steer physicians in right direction
      through CME on right indications, duration of therapy and replacement fluid.
      Therefore, authors reviewed, collated, and interpreted effect of formal CME
      interventions. MATERIALS AND METHODS: Retrospective study was conducted in a
      large hospital in India. CME interventions to teach clinical and managerial
      aspects of TA were conducted in the first quarter of 2012. Sessions involved ASFA
      guidelines and recommendations for TA. Data was collected and changes in practice
      related to TA before (March 2010 to December 2011) and after (April 2012 to
      December 2013) the intervention was analyzed. RESULTS: Seventy-three subjects
      participated in the interventions. Five hundred and eighty-nine TA procedures
      were performed during study period; 214 procedures in 49 patients before
      intervention and 375 procedures in 84 patients after intervention. After
      intervention there was significant improvement in indications of category I
      (38.7% vs. 64.3%; P = 0.004), category II (22.5% vs. 16.6%), category III (12.2%
      vs. 11.9%), and category IV (6.1% vs. 2.4%; P = 0.0001). Significant reduction
      was seen in procedures not belonging to any category from 20.5% to 4.8% (P =
      0.002). Change in practices was also observed in context of duration of therapy
      and replacement fluid. CONCLUSION: CME intervention, based on the 2010 edition of
      ASFA guidelines for therapeutic apheresis appears to have had a positive impact
      on physicians TA practices.

PMID- 25858285
TI  - Using Ontology Fingerprints to disambiguate gene name entities in the biomedical
      literature.
AB  - Ambiguous gene names in the biomedical literature are a barrier to accurate
      information extraction. To overcome this hurdle, we generated Ontology
      Fingerprints for selected genes that are relevant for personalized cancer
      therapy. These Ontology Fingerprints were used to evaluate the association
      between genes and biomedical literature to disambiguate gene names. We obtained
      93.6% precision for the test gene set and 80.4% for the area under a receiver
      operating characteristics curve for gene and article association. The core
      algorithm was implemented using a graphics processing unit-based MapReduce
      framework to handle big data and to improve performance. We conclude that
      Ontology Fingerprints can help disambiguate gene names mentioned in text and
      analyse the association between genes and articles. Database URL:
      http://www.ontologyfingerprint.org

PMID- 25858287
TI  - What doctors have in common with architects--part 2: the common good.

PMID- 25858286
TI  - miRGate: a curated database of human, mouse and rat miRNA-mRNA targets.
AB  - MicroRNAs (miRNAs) are small non-coding elements involved in the post
      transcriptional down-regulation of gene expression through base pairing with
      messenger RNAs (mRNAs). Through this mechanism, several miRNA-mRNA pairs have
      been described as critical in the regulation of multiple cellular processes,
      including early embryonic development and pathological conditions. Many of these
      pairs (such as miR-15 b/BCL2 in apoptosis or BART-6/BCL6 in diffuse large B-cell
      lymphomas) were experimentally discovered and/or computationally predicted.
      Available tools for target prediction are usually based on sequence matching,
      thermodynamics and conservation, among other approaches. Nevertheless, the main
      issue on miRNA-mRNA pair prediction is the little overlapping results among
      different prediction methods, or even with experimentally validated pairs lists,
      despite the fact that all rely on similar principles. To circumvent this problem,
      we have developed miRGate, a database containing novel computational predicted
      miRNA-mRNA pairs that are calculated using well-established algorithms. In
      addition, it includes an updated and complete dataset of sequences for both miRNA
      and mRNAs 3'-Untranslated region from human (including human viruses), mouse and
      rat, as well as experimentally validated data from four well-known databases. The
      underlying methodology of miRGate has been successfully applied to independent
      datasets providing predictions that were convincingly validated by functional
      assays. miRGate is an open resource available at http://mirgate.bioinfo.cnio.es.
      For programmatic access, we have provided a representational state transfer web
      service application programming interface that allows accessing the database at
      http://mirgate.bioinfo.cnio.es/API/ Database URL: http://mirgate.bioinfo.cnio.es

PMID- 25858288
TI  - Antiplasmodial activity of aqueous extract of Berberis aristata roots against
      Plasmodium berghei-infected BALB/c mice.
AB  - CONTEXT: The rising problem of resistance to present antimalarial drugs stresses
      the need to look for newer antiplasmodial components with effective modes of
      action. The roots of Berberis aristata DC. (Berberidaceae) are used in the
      traditional medicine for malaria in various parts of India. OBJECTIVE: The
      objective of this study was to evaluate antiplasmodial activity of B. aristata
      roots extract for the validation of its traditional medicinal use. MATERIAL AND
      METHODS: Aqueous root extract of Berberis aristata (AREBA) was screened for its
      in vitro as well as in vivo antiplasmodial activity against lethal rodent malaria
      parasite Plasmodium berghei NK65. In vitro activity was evaluated against
      schizont maturation of P. berghei using various concentrations ranging from 1 to
      100 ug/mL. For in vivo studies, AREBA at the doses of 150, 250, 350, and 650
      mg/kg/d was administered to P. berghei infected BALB/c mice orally for 4
      consecutive days (D0-D3). RESULTS: AREBA showed in vitro antiplasmodial activity
      with an IC50 value of 40 ug/mL. In vivo studies demonstrated a variable dose
      dependent chemosuppression with higher efficacy at lower doses. At a dose of 350
      mg/kg/d, the suppressive and preventive activities were found to be 67.1% and
      53.9%, respectively, followed by enhancing mean survival period up to 12.8 d for
      the curative assay versus 7.5 d for the untreated mice. DISCUSSION AND
      CONCLUSION: These results provide relevant scientific evidences for the
      traditional medicinal use of this plant as malaria remedy and further advocates
      the isolation and characterization of active antiplasmodial principle from this
      plant.

PMID- 25858290
TI  - Atopic allergic conditions and colorectal cancer risk in the Multiethnic Cohort
      Study.
AB  - Studies have provided evidence of an inverse association between atopic allergic
      conditions (AACs) and invasive colorectal cancer (CRC) incidence and mortality in
      predominantly white populations. We examined the association between AACs
      (asthma, hay fever, or allergy) and CRC among white, African-American, Native
      Hawaiian, Japanese-American, and Latino men and women in the Multiethnic Cohort
      Study within Hawaii and Los Angeles, California. The prospective analysis
      included 4,834 incident CRC cases and 1,363 CRC-related deaths ascertained
      between 1993 and 2010. We examined associations by ethnicity, location, stage,
      and potential effect modification by CRC risk factors. AACs were associated with
      a reduced risk of CRC incidence among both men and women (relative risk (RR) =
      0.86, 95% confidence interval (CI): 0.80, 0.92). The reduction in risk was noted
      in all populations except Latinos and was significant in whites (RR = 0.85, 95%
      CI: 0.73, 0.98), African Americans (RR = 0.81, 95% CI: 0.70, 0.95), Native
      Hawaiians (RR = 0.72, 95% CI: 0.54, 0.96), and Japanese Americans (RR = 0.87, 95%
      CI: 0.78, 0.98). Individuals with AACs also had a 20% reduction in CRC-related
      mortality (P = 0.001). These findings provide evidence for the potential
      protective role of the reactive immune system in colorectal cancer. 

PMID- 25858291
TI  - Parental reasoning about growth attenuation therapy: report of a single-case
      study.
AB  - In 2006 a case report was published about a 6-year-old girl, Ashley, who has
      profound developmental disabilities and was treated with oestrogen patches to
      limit her final height, along with a hysterectomy and the removal of her breast
      buds. Ashley's parents claimed that attenuating her growth would make it possible
      for them to lift and move her more easily, facilitating greater involvement in
      family activities and making routine care more straightforward. The 'Ashley
      treatment' provoked public comment and academic debate and remains ethically
      controversial. As more children are being referred for such treatment, there is
      an urgent need to clarify how clinicians and ethics committees should respond to
      such requests. The controversy surrounding the Ashley treatment exists, at least
      in part, because of gaps in the literature, including a lack of empirical data
      about the outcomes for children who do and do not receive such treatment.
      However, we suggest in this paper that there is also merit in examining the
      parental decision-making process itself, and provide empirical data about the
      reasoning of one set of parents who ultimately chose part of this treatment for
      their child. Using the interview data, we illuminate some important points
      regarding how these parents characterise benefits and harms and their
      responsibilities as surrogate decision-makers. This analysis could inform
      decision-making about future requests for growth attenuation and might also have
      wider relevance to healthcare decision-making for children with profound
      cognitive impairment. 

PMID- 25858289
TI  - Indoor tanning and the MC1R genotype: risk prediction for basal cell carcinoma
      risk in young people.
AB  - Basal cell carcinoma (BCC) incidence is increasing, particularly in young people,
      and can be associated with significant morbidity and treatment costs. To identify
      young individuals at risk of BCC, we assessed existing melanoma or overall skin
      cancer risk prediction models and built a novel risk prediction model, with a
      focus on indoor tanning and the melanocortin 1 receptor gene, MC1R. We evaluated
      logistic regression models among 759 non-Hispanic whites from a case-control
      study of patients seen between 2006 and 2010 in New Haven, Connecticut. In our
      data, the adjusted area under the receiver operating characteristic curve (AUC)
      for a model by Han et al. (Int J Cancer. 2006;119(8):1976-1984) with 7 MC1R
      variants was 0.72 (95% confidence interval (CI): 0.66, 0.78), while that by Smith
      et al. (J Clin Oncol. 2012;30(15 suppl):8574) with MC1R and indoor tanning had an
      AUC of 0.69 (95% CI: 0.63, 0.75). Our base model had greater predictive ability
      than existing models and was significantly improved when we added ever-indoor
      tanning, burns from indoor tanning, and MC1R (AUC = 0.77, 95% CI: 0.74, 0.81).
      Our early-onset BCC risk prediction model incorporating MC1R and indoor tanning
      extends the work of other skin cancer risk prediction models, emphasizes the
      value of both genotype and indoor tanning in skin cancer risk prediction in young
      people, and should be validated with an independent cohort. 

PMID- 25858292
TI  - Increased peak gamma frequency in individuals with higher levels of autistic
      traits.
AB  - Individual differences in orientation discrimination threshold are related to
      both visually-induced peak gamma frequency and the presence of autistic traits.
      The relationship between peak gamma frequency and orientation discrimination
      thresholds may be due to both of these factors being mediated by levels of neural
      inhibition. No study has previously measured the relationship between peak gamma
      frequency and levels of autistic traits. Thus, this was the aim of the present
      study. We measured orientation discrimination thresholds and autistic traits in a
      neurotypical human sample (N = 33), and separately recorded
      electroencephalography to measure visually induced gamma activity. In line with
      our prediction, we found a significant relationship between peak gamma frequency
      and level of autistic traits. Consistent with previous work we also found
      significant relationships between orientation discrimination thresholds and level
      of autistic traits and between orientation discrimination thresholds and peak
      gamma frequency. Our results demonstrate that individuals with individuals with
      higher levels of autistic personality traits have a higher peak-gamma frequency
      and are better at discriminating between visual stimuli based on orientation. As
      both higher peak gamma frequency and lower orientation discrimination thresholds
      have been linked to higher levels of neural inhibition, this suggests that
      autistic traits co-occur with increased neural inhibition. This discovery is
      significant as it challenges the currently-held view that autism spectrum
      conditions are associated with increased neural excitation. 

PMID- 25858293
TI  - Acute myeloid leukaemia: challenges and real world data from India.
AB  - The management of acute myeloid leukaemia (AML) in India remains a challenge. In
      a two-year prospective study at our centre there were 380 newly diagnosed AML
      (excluding acute promyelocytic leukaemia, AML-M3) patients. The median age of
      newly diagnosed patients was 40 years (range: 1-79; 12.3% were <= 15 years, 16.3%
      were >= 60 years old) and there were 244 (64.2%) males. The median duration of
      symptoms prior to first presentation at our hospital was 4 weeks (range: 1-52).
      The median distance from home to hospital was 580 km (range: 6-3200 km). 109
      (29%) opted for standard of care and were admitted for induction chemotherapy. Of
      the 271 that did not take treatment the major reason was lack of financial
      resources in 219 (81%). There were 27 (24.7%) inductions deaths and of these, 12
      (44.5%) were due to multidrug-resistant gram-negative bacilli and 12 (44.5%)
      showed evidence of a fungal infection. The overall survival at 1 year was 70.4%
      +/- 10.7%, 55.6% +/- 6.8% and 42.4% +/- 15.6% in patients aged <= 15 years, 15 -
      60 years and >= 60 years, respectively. In conclusion, the biggest constraint is
      the cost of treatment and the absence of a health security net to treat all
      patients with this diagnosis.

PMID- 25858294
TI  - Functional brain changes underlying irritability in premanifest Huntington's
      disease.
AB  - The clinical phenotype of Huntington's disease (HD) consists of motor, cognitive
      and psychiatric symptoms, of which irritability is an important manifestation.
      Our aim was to identify the functional and structural brain changes that underlie
      irritability in premanifest HD (preHD). Twenty preHD carriers and 20 gene
      negative controls from HD families took part in the study. Although the 5-year
      probability of disease onset was only 11%, the preHD group showed striatal
      atrophy and increased clinical irritability ratings. Functional MRI was performed
      during a mood induction experiment by means of recollection of emotional (angry,
      sad, and happy) and neutral autobiographical episodes. While there were no
      significant group differences in the subjective intensity of the emotional
      experience, the preHD group showed increased anger-selective activation in a
      distributed network, including the pulvinar, cingulate cortex, and somatosensory
      association cortex, compared to gene-negative controls. Pulvinar activation
      during anger experience correlated negatively with putaminal grey matter volume
      and positively with irritability ratings in the preHD group. In addition, the
      preHD group showed a decrease in anger-selective activation in the amygdala,
      which correlated with putaminal and caudate grey matter volume. In conclusion,
      compared to gene-negative controls, anger experience in preHD is associated with
      activity changes in a distributed set of regions known to be involved in emotion
      regulation. Increased activity is related to behavioral and volumetric measures,
      providing insight in the pathophysiology of early neuropsychiatric symptoms in
      preHD.

PMID- 25858295
TI  - All-dielectric multilayer cylindrical structures for invisibility cloaking.
AB  - We study optical response of all-dielectric multilayer structures and demonstrate
      that the total scattering of such structures can be suppressed leading to optimal
      invisibility cloaking. We use experimental material data and a genetic algorithm
      to reduce the total scattering by adjusting the material and thickness of various
      layers for several types of dielectric cores at telecommunication wavelengths.
      Our approach demonstrates 80-fold suppression of the total scattering cross
      section by employing just a few dielectric layers. 

PMID- 25858296
TI  - Ultralow Density, Monolithic WS2, MoS2, and MoS2/Graphene Aerogels.
AB  - We describe the synthesis and characterization of monolithic, ultralow density
      WS2 and MoS2 aerogels, as well as a high surface area MoS2/graphene hybrid
      aerogel. The monolithic WS2 and MoS2 aerogels are prepared via thermal
      decomposition of freeze-dried ammonium thio-molybdate (ATM) and ammonium thio
      tungstate (ATT) solutions, respectively. The densities of the pure dichalcogenide
      aerogels represent 0.4% and 0.5% of full density MoS2 and WS2, respectively, and
      can be tailored by simply changing the initial ATM or ATT concentrations. Similar
      processing in the presence of the graphene aerogel results in a hybrid structure
      with MoS2 sheets conformally coating the graphene scaffold. This layered motif
      produces a ~50 wt % MoS2 aerogel with BET surface area of ~700 m(2)/g and an
      electrical conductivity of 112 S/m. The MoS2/graphene aerogel shows promising
      results as a hydrogen evolution reaction catalyst with low onset potential (~100
      mV) and high current density (100 mA/cm(2) at 260 mV). 

PMID- 25858297
TI  - Internet-based remote health self-checker symptom data as an adjuvant to a
      national syndromic surveillance system.
AB  - Syndromic surveillance is an innovative surveillance tool used to support
      national surveillance programmes. Recent advances in the use of internet-based
      health data have demonstrated the potential usefulness of these health data;
      however, there have been limited studies comparing these innovative health data
      to existing established syndromic surveillance systems. We conducted a
      retrospective observational study to assess the usefulness of a national internet
      based 'symptom checker' service for use as a syndromic surveillance system. NHS
      Direct online data were extracted for 1 August 2012 to 1 July 2013; a time-series
      analysis on the symptom categories self-reported by online users was undertaken
      and compared to existing telehealth syndromic data. There were 3.37 million
      online users of the internet-based self-checker compared to 1.43 million callers
      to the telephone triage health service. There was a good correlation between the
      online and telephone triage data for a number of syndromic indicators including
      cold/flu, difficulty breathing and eye problems; however, online data appeared to
      provide additional early warning over telephone triage health data. This
      assessment has illustrated some potential benefit of using internet-based symptom
      checker data and provides the basis for further investigating how these data can
      be incorporated into national syndromic surveillance programmes. 

PMID- 25858298
TI  - Fortuitous description of haemoglobin A2' [delta16 (A13) Gly->Arg (GGC->CGC)] in
      a Tunisian family: study of the molecular defect and its origin.
AB  - The most common inherited haemoglobin disorders encountered in Tunisia are beta
      thalassemia and sickle cell disease, which result from mutations in the beta
      globin gene. Few studies focused on delta-globin gene variations responsible for
      delta-thalassemia or HbA2 variants. HbA2' [delta16 (A13) Gly->Arg (GGC->CGC)] is
      a delta-chain variant that has been identified in several populations of African
      origin. We report herein for the first time the description of HbA2' in the
      Tunisian population. Identification of HbA2' in the studied family was carried
      out by high-performance liquid chromatography and confirmed by sequencing
      analyses of the whole delta-globin gene. Haplotypes of the beta-globin gene
      cluster were constructed by mapping the restriction sites using polymerase chain
      reaction followed by enzymatic digestion. Compound heterozygosity of HbA2' with
      HbO-Arab was identified in the proband. The mother and two other siblings showed
      heterozygous HbA2' whereas the father showed heterozygous HbO-Arab. The sum of
      HbA2 and HbA2' in all cases was less than 4%, thus excluding beta-thalassemia.
      beta-cluster haplotype analysis revealed that this mutation was associated with
      the F haplotype (-+--+++). The unique origin of this mutation in Africa is likely
      since the linked beta-cluster haplotype is one of the major haplotypes found in
      African populations. 

PMID- 25858299
TI  - Tracking camera control in endoscopic dacryocystorhinostomy surgery.
AB  - OBJECTIVES: Poor camera control during endoscopic dacryocystorhinostomy (EnDCR)
      surgery can cause inadequate visualisation of the anatomy and suboptimal surgical
      outcomes. This study investigates the feasibility of using computer vision
      tracking in EnDCR surgery as a potential formative feedback tool for the quality
      of endoscope control. DESIGN: A prospective cohort analysis was undertaken
      comparing junior versus senior surgeons performing routine EnDCR surgery.
      Computer vision tracking was applied to endoscopic video footage of the surgery:
      Total number of movements, camera path length in pixels and surgical time were
      determined for each procedure. A Mann-Whitney U-test was used to test for a
      significant difference between juniors and seniors (P < 0.05). SETTING: Operating
      theatre. PARTICIPANTS: Ten junior surgeons (<20 completed procedures) and 10
      senior surgeons (>100 completed procedures). MAIN OUTCOME MEASURES: Total number
      of movements of the endoscope per procedure. Path length of the endoscope per
      procedure. RESULTS: Twenty videos, 10 from junior surgeons and 10 from senior
      surgeons were analysed. Feasibility of our tracking system was demonstrated. Mean
      camera path lengths were significantly different at 119,329px (juniors) versus
      43,697px (seniors), P ? 0.05. The mean number of movements was significantly
      different at 9134 (juniors) versus 3690 (seniors), P ? 0.05. These quantifiable
      differences demonstrate construct validity for computer vision endoscope tracking
      as a measure of surgical experience. CONCLUSIONS: Computer vision tracking is a
      potentially useful structured and objective feedback tool to assist trainees in
      improving endoscope control. It enables juniors to examine how their pattern of
      endoscope control differs from that of seniors, focusing in particular on
      sections where they are most divergent.

PMID- 25858300
TI  - Effects of the F-actin inhibitor latrunculin A on the budding yeast Saccharomyces
      cerevisiae.
AB  - Our basic cell biology research was aimed at investigating the effect on
      eukaryotic cells of the sudden loss of the F-actin cytoskeleton. Cells treated
      with latrunculin A (LA) in yeast extract peptone dextrose (YEPD) medium were
      examined using phase-contrast and fluorescent microscopy, freeze-substitution,
      transmission and scanning electron microscopy, counted using a Burker chamber and
      their absorbance measured. The cells responded to the presence of LA, an F-actin
      inhibitor, with the disappearance of actin patches, actin cables and actin rings.
      This resulted in the formation of larger spherical cells with irregular
      morphology in the cell walls and ultrastructural disorder of the cell organelles
      and secretory vesicles. Instead of buds, LA-inhibited cells formed only 'table
      mountain-like' wide flattened swellings without apical growth with a thinner
      glucan cell-wall layer containing beta-1,3-glucan microfibrils. The LA-inhibited
      cells lysed. Actin cables and patches were required for bud formation and bud
      growth. In addition, actin patches were required for the formation of beta-1,3
      glucan microfibrils in the bud cell wall. LA has fungistatic, fungicidal and
      fungilytic effects on the budding yeast Saccharomyces cerevisiae. 

PMID- 25858301
TI  - Experimental and Theoretical Data on the Mechanism by Which Red Wine Anthocyanins
      Are Transported through a Human MKN-28 Gastric Cell Model.
AB  - The gastric absorption of red wine anthocyanins was evaluated using a gastric MKN
      28 cell barrier model. Anthocyanin transport was not affected by the presence of
      4% ethanol and decreased with the increase of pH. Gastric cells pretreated with
      anthocyanins were found to increase anthocyanin transport. The presence of d-(+)
      glucose was found to decrease anthocyanin uptake, suggesting the involvement of
      glucose transporters. RT-PCR assays revealed that GLUT1, GLUT3, and MCT1
      transporters were expressed in MKN-28 cells. Computational studies were performed
      to provide a structural characterization of the binding site of hGLUT1 to glucose
      or different anthocyanins under different forms. Docking results demonstrated
      that anthocyanins can bind to glucose transporters from both intracellular and
      extracellular sides. Anthocyanins seem to enter into the transporter by two main
      conformations: B ring or glucose. From MD simulations, hGLUT1 was found to form
      complexes with all anthocyanins tested in the different protonation states. 

PMID- 25858302
TI  - Anti-Toxoplasma activity of natural products: a review.
AB  - Toxoplasma gondii is an intracellular parasite widely distributed in nature.
      Infection is asymptomatic in immunocompetent individuals; however, various
      clinical manifestations may occur in immunocompromised individuals. Although
      there are medications for the treatment of toxoplasmosis, such as pyrimethamine
      and sulfonamide, they cannot always be used due to adverse reactions or to
      therapeutic failures related to intolerance or malabsorption of drugs and to
      parasite drug resistance. In recent years, the search for new antimicrobial
      agents derived from plants has intensified because a quarter of synthetic drugs
      that are currently prescribed have been isolated from a plant source,
      demonstrating that natural products are important in the development of new
      drugs. A systematic literature search was conducted to evaluate the use of
      natural products as an alternative for the treatment of T. gondii infection. The
      search was conducted for the 2000-2014 period in Science Direct, Scopus, PubMed,
      EMBASE, and SciELO databases, using the following MeSH terms: anti-Toxoplasma
      activity, toxoplasma AND natural products, toxoplasma AND plant extracts.
      Ethnobotanical and experimental evidence (in vitro/in vivo) was found supporting
      the use of natural products as a source for the discovery of new therapies
      against T. gondii. 

PMID- 25858303
TI  - Ocular toxocariasis: new diagnostic and therapeutic perspectives.
AB  - PURPOSE: To provide an updated insight of concepts regarding the overview,
      epidemiology, risk factors, clinical manifestations, diagnosis, treatment and
      prevention of ocular toxocariasis. DESIGN: Perspective of literature review.
      METHODS: Review and synthesis of literature about toxocariasis, with
      interpretation and perspective. A literature search for "ocular toxocariasis" was
      performed using PubMed, ScienceDirect, Scopus, SciELO and LILACS databases.
      RESULTS: Mild to moderate infections are frequently reported in ocular
      toxocariasis which usually occurs in children and typically presents as
      unilateral vision impairment, blindness is common and could present invasion of
      the retina. There are three groups of presentation of toxocariasis (according to
      the physical examination): chronic endophthalmitis, posterior granuloma and
      peripheral granuloma. Standard diagnosis of ocular toxocariasis is based on the
      identification of clinical signs, supported by additional diagnostic methods.
      Regarding treatment, there is no commonly accepted regimen but most of the
      authors prefer to use steroids and anthelminthic agents, but nowadays there are
      no standardized parameters in terms of dosage, duration and route of
      administration. Surgery has been recommended in some cases. CONCLUSION:
      Toxocariasis is still a problem of public health, particularly in developing
      countries with an increasing epidemiological burden in terms of morbidity and
      mortality and most of the authors agree on the utmost relevance of its
      prevention. Clinical experience and suspicion of ophthalmologists make an
      important role in its diagnosis, but always with supportive diagnostic methods.
      Additional studies should explore new therapeutic options for toxocariasis.

PMID- 25858304
TI  - The present situation of human taeniases and cysticercosis in Asia.
AB  - Three human Taenia species, Taenia solium, Taenia saginata, and Taenia asiatica,
      are endemic in rural regions of Asia, with these species sympatrically
      distributed in parts of Thailand and China. The pork tapeworm, T. solium, is the
      most pathogenic to humans, causing cysticercosis and neurocysticercosis (NCC).
      Due to its public health impact, T. solium taeniasis/cysticercosis is one of 17
      neglected tropical diseases (NTDs) prioritized by the World Health Organization.
      In this review, the current status of taeniasis and NCC in several Asian
      countries will be presented as will possible prevention and control strategies.
      Among the known T. solium endemic areas in Asia, Bali, Indonesia is of high
      importance due to the risk of tourists becoming infected. Therefore, special
      attention will be given to ongoing control initiatives in Bali. 

PMID- 25858305
TI  - Rabies in South Asia: fighting for elimination.
AB  - South Asia is regarded as the hot spot for the tourist and travelers.
      Unfortunately, three big countries (India, Pakistan and Bangladesh) of this
      region belong to top five rabies endemic countries of the world. Around 55,000
      people die of rabies every year globally and 45% of them belong to South and
      South East Asia. Countries are now working on the elimination of rabies by the
      year 2020. Elimination of animal rabies is the pivotal of controlling human
      rabies. Dog (primary source) registration, population control and mass
      vaccination are the different ways of eliminating animal rabies. Pre (for risk
      groups including travelers) and post-exposure vaccine is the core for controlling
      human rabies. Post-exposure vaccine consists of nerve tissue vaccine and tissue
      culture vaccine. Due to low antigenicity and post-vaccine neurological
      complications all countries of South Asia except Pakistan have phased out the
      production and use of nerve tissue vaccine. To reduce the cost intramuscular
      regimen is now largely replaced by intradermal regimen and equine rabies
      immunoglobulin will probably replace human immunoglobulin in future for category
      III animal bite. 'SAARC' took initiatives for rabies elimination through 'SAARC
      development fund' which would hopefully play a vital role in regional
      collaboration to make the region rabies free. 

PMID- 25858306
TI  - Geographical and occupational aspects of leptospirosis in the coffee-triangle
      region of Colombia, 2007-2011.
AB  - BACKGROUND: There are few studies occupationally profiling as well as using
      Geographic information system (GIS) to map human leptospirosis. There are no
      detailed, municipality-level, epidemiological maps in Colombia neither in South
      America. We developed such maps for the Coffee-triangle region, Colombia and
      assess some occupational issues. METHODS: surveillance cases data (2007-2011)
      were used to estimate the annual incidence rates (cases/100,000 population) of
      leptospirosis to develop the first maps of disease in the 53 municipalities of
      the Coffee-triangle region of Colombia. GIS used was Kosmo((r)) 3.1. Five
      thematic maps were developed according to municipalities and years. Using labor
      official information, analyses between agriculture (harvested areas) with disease
      occurrence was done (linear regression). RESULTS: Between 2007 and 2011, 786
      cases were reported (77.8% from one department, Risaralda), for a cumulated rate
      of 32.18 cases/100,000 population. The highest rate was reported in the less
      developed municipality of one department (Pueblo Rico, Risaralda) with 1535.05
      cases/100,000 population (187 cases, 2009). Armenia (Quindio department capital
      city), reported 23.41 cases/100,000pop (2011). In those patients with identified
      occupations, 33.3% were agriculture workers, finding a significant relationship
      between the number of cases in 2008 and the harvested area by municipality
      (r(2)=0.48; p=0.0083). CONCLUSION: one of the 53 municipalities contributed with
      almost a quarter of the cases. Agriculture was significantly associated with the
      incidence. Use of GIS-based epidemiological maps allow to focus actions in
      prevention and control for risk zones for leptospirosis which still represents a
      significant issue in the region and Colombia, particularly in agriculture
      workers.

PMID- 25858307
TI  - Variation in health care-associated infection surveillance practices in
      Australia.
AB  - In the absence of a national health care-associated infection surveillance
      program in Australia, differences between existing state-based programs were
      explored using an online survey. Only 51% of respondents who undertake
      surveillance have been trained, fewer than half perform surgical site infection
      surveillance prospectively, and only 41% indicated they risk adjust surgical site
      infection data. Widespread variation of surveillance methods highlights future
      challenges when considering the development and implementation of a national
      program in Australia. 

PMID- 25858308
TI  - Identifying changes in the role of the infection preventionist through the 2014
      practice analysis study conducted by the Certification Board of Infection Control
      and Epidemiology, Inc.
AB  - The Certification Board of Infection Control and Epidemiology, Inc (CBIC) is a
      voluntary autonomous multidisciplinary board that provides direction and
      administers the certification process for professionals who are responsible for
      the infection prevention and control program in a health care facility. The CBIC
      performs a practice analysis approximately every 4-5 years. The practice analysis
      is an integral part of the certification examination development process and
      serves as the backbone of the test content outline. In 2013, the CBIC determined
      that a practice analysis was required and contracted with Prometric to facilitate
      the process. The practice analysis was carried out in 2014 by a diverse group of
      subject matter experts from the United States and Canada. The practice analysis
      results showed a significant change in the number of tasks and associated
      knowledge required for the competent practice of infection prevention. As
      authorized by the CBIC, the test committee is currently reclassifying the bank of
      examination questions as required and is writing and reviewing questions based on
      the updated test specifications and content outline. The new content outline will
      be reflected in examinations that are taken beginning in July 2015. This
      iterative process of assessing and updating the certification examination ensures
      not only a valid competency tool but a true reflection of current practices. 

PMID- 25858309
TI  - Parenting stress in mothers with cystic fibrosis.
AB  - AIM: To assess the parenting experience of mothers with cystic fibrosis (CF) and
      to compare with normative data. METHODS: Cross-sectional study with a validated
      generic parental stress questionnaire (PSQ). This PSQ differentiates four
      components of parental stress: main factor "parental stress", compounding factor
      "role restrictions", protective factors "support from spouse", and "social
      support". Cut-off scores categorise results as "normal", "borderline" or
      "concerning". SAMPLE: Seventy-three women were informed by their local CF centre.
      Of these, 36 enrolled and had a first-born child aged 1-12 years (consistent with
      reference values of the PSQ). Of these, 31 (86%) returned the PSQ. Mean age of
      mothers was 32.6 years +/- 6.9 years, mean age of first-born child was 5.2 years
      +/- 3.4 years. Most of the mothers had one biological child, five women had two
      children and one had three children. RESULTS: Parental stress scores were
      normally distributed, the same applies for contributing factors and for the two
      protective factors. Favourable scores were twice as frequent as concerning
      scores. Mothers of younger children scored slightly better than mothers of school
      aged children. CONCLUSION: In line with the only comparable study, mothers with
      CF seem to be a remarkably resilient group who mostly cope well with parental
      stress even in the face of a progressive, chronic disease requiring time
      consuming treatment. IMPLICATIONS FOR REHABILITATION: Today, motherhood is
      increasingly becoming an option in fertile women with cystic fibrosis. The
      additional burden of parenting seems to be rewarded by fulfilling essential
      personal goals. CF clinics should routinely address a possible wish for a child
      and to discuss it, openly.

PMID- 25858310
TI  - Oxalic acid: a signal molecule for fungus-feeding bacteria of the genus
      Collimonas?
AB  - Mycophagous (=fungus feeding) soil bacteria of the genus Collimonas have been
      shown to colonize and grow on hyphae of different fungal hosts as the only source
      of energy and carbon. The ability to exploit fungal nutrient resources might
      require a strategy for collimonads to sense fungi in the soil matrix. Oxalic acid
      is ubiquitously secreted by soil fungi, serving different purposes. In this
      study, we investigated the possibility that collimonads might use oxalic acid
      secretion to localize a fungal host and move towards it. We first confirmed
      earlier indications that collimonads have a very limited ability to use oxalic
      acid as growth substrate. In a second step, with using different assays, we show
      that oxalic acid triggers bacterial movement in such a way that accumulation of
      cells can be expected at micro-sites with high free oxalic acid concentrations.
      Based on these observations we propose that oxalic acid functions as a signal
      molecule to guide collimonads to hyphal tips, the mycelial zones that are most
      sensitive for mycophagous bacterial attack. 

PMID- 25858311
TI  - Three-dimensional grammar in the brain: Dissociating the neural correlates of
      natural sign language and manually coded spoken language.
AB  - In several countries natural sign languages were considered inadequate for
      education. Instead, new sign-supported systems were created, based on the belief
      that spoken/written language is grammatically superior. One such system called
      SJM (system jezykowo-migowy) preserves the grammatical and lexical structure of
      spoken Polish and since 1960s has been extensively employed in schools and on TV.
      Nevertheless, the Deaf community avoids using SJM for everyday communication, its
      preferred language being PJM (polski jezyk migowy), a natural sign language,
      structurally and grammatically independent of spoken Polish and featuring
      classifier constructions (CCs). Here, for the first time, we compare, with fMRI
      method, the neural bases of natural vs. devised communication systems. Deaf
      signers were presented with three types of signed sentences (SJM and PJM
      with/without CCs). Consistent with previous findings, PJM with CCs compared to
      either SJM or PJM without CCs recruited the parietal lobes. The reverse
      comparison revealed activation in the anterior temporal lobes, suggesting
      increased semantic combinatory processes in lexical sign comprehension. Finally,
      PJM compared with SJM engaged left posterior superior temporal gyrus and anterior
      temporal lobe, areas crucial for sentence-level speech comprehension. We suggest
      that activity in these two areas reflects greater processing efficiency for
      naturally evolved sign language. 

PMID- 25858313
TI  - Expression and biochemical characterization of light chains of Botulinum
      neurotoxin subtypes F5 and F7.
AB  - Botulinum neurotoxins are the most potent protein toxins known to human. To date,
      seven subtypes of the BoNT/F serotype (BoNT/F1 to BoNT/F7) have been identified,
      among which BoNT/F5 and BoNT/F7 are the most divergent. However, little
      structural and functional information is available for these two subtypes due to
      a lack of suitable recombinant proteins for biochemical characterization, except
      that they appear to possess unique substrate recognition mechanisms, thereby
      impeding development of vaccine or inhibitors against these proteins. In the
      present study, we utilized a combinatorial approach which involved examining the
      effects of different affinity tags, mapping C-terminal truncation mutants and
      optimization of expression and purification conditions, that allowed us to
      successfully express and purify soluble and highly active recombinant LC/F5 and
      LC/F7 proteins. GST-LC/F5(1-450) and 6* His-LC/F5(1-405) were the formats which
      exhibit the highest level of solubility and activity, whereas GST-LC/F7(1-405)
      was the most active form of LC/F7. In comparison, GST-LC/F5(1-450) was more
      active than GST-LC/F7(1-405), which was in turn more active than the LC/F1
      control. Our data suggest that solubility of these proteins strongly correlated
      with their catalytic activity. Successful expression and purification of LC/F5
      and LC/F7 in this work will, for the first time, provide materials for further
      characterization of these two subtypes of BoNT/F, which is essential for future
      development of protective vaccine or other therapeutic strategies, as well as
      BoNT/F protein engineering. 

PMID- 25858312
TI  - Neuropsychiatric lupus: a mosaic of clinical presentations.
AB  - Neuropsychiatric symptoms affect nearly half of the patients with systemic lupus
      erythematosus; however, the effect on disease severity, quality of life, and
      prognosis is tremendous. Symptoms of neuropsychiatric systemic lupus
      erythematosus may range from mild diffuse ones, to acute life threatening events.
      Although the underlying mechanisms are still largely unraveled, several
      pathogenic pathways are identified, such as antibody-mediated neurotoxicity,
      vasculopathy due to anti-phospholipid antibodies and other mechanisms, and
      cytokine-induced neurotoxicity. In the current review, we describe the old and
      the new regarding epidemiology, pathophysiology, diagnosis, and management of
      neuropsychiatric systemic lupus erythematosus. The possible link between
      neuropsychiatric symptoms and specific mechanisms may help to facilitate our
      understanding of the disease in the future, thus allowing for better treatment
      strategies. 

PMID- 25858314
TI  - Purification of galectin-1 mutants using an immobilized Galactosebeta1-4Fucose
      affinity adsorbent.
AB  - Galectins are a family of lectins characterized by their carbohydrate recognition
      domains containing eight conserved amino acid residues, which allows the binding
      of galectin to beta-galactoside sugars such as Galbeta1-4GlcNAc. Since galectin
      glycan interactions occur extracellularly, recombinant galectins are often used
      for the functional analysis of these interactions. Although it is relatively easy
      to purify galectins via affinity to Galbeta1-4GlcNAc using affinity adsorbents
      such as asialofetuin-Sepharose, it could be difficult to do so with mutated
      galectins, which may have reduced affinity towards their endogenous ligands.
      However, this is not the case with Caenorhabditis elegans galectin LEC-6; binding
      to its endogenous recognition unit Galbeta1-4Fuc, a unique disaccharide found
      only in invertebrates, is not necessarily affected by point mutations of the
      eight well-conserved amino acids. In this study, we constructed mutants of mouse
      galectin-1 carrying substitutions of each of the eight conserved amino acid
      residues (H44F, N46D, R48H, V59A, N61D, W68F, E71Q, and R73H) and examined their
      affinity for Galbeta1-4GlcNAc and Galbeta1-4Fuc. These mutants, except W68F, had
      very low affinity for asialofetuin-Sepharose; however, most of them (with the
      exception of H44F and R48H) could be purified using Galbeta1-4Fuc-Sepharose. The
      affinity of the purified mutant galectins for glycans containing Galbeta1-4Fuc or
      Galbeta1-4GlcNAc moieties was quantitatively examined by frontal affinity
      chromatography, and the results indicated that the mutants retained the affinity
      only for Galbeta1-4Fuc. Given that other mammalian galectins are known to bind
      Galbeta1-4Fuc, our data suggest that immobilized Galbeta1-4Fuc ligands could be
      generally used for easy one-step affinity purification of mutant galectins. 

PMID- 25858315
TI  - Cloning and characterization of HbMT2a, a metallothionein gene from Hevea
      brasiliensis Muell. Arg differently responds to abiotic stress and heavy metals.
AB  - Metallothioneins (MTs) are of low molecular mass, cysteine-rich proteins. They
      play an important role in the detoxification of heavy metals and homeostasis of
      intracellular metal ions, and protecting against intracellular oxidative damages.
      In this study a full-length cDNA of type 2 plant metallothioneins, HbMT2a, was
      isolated from 25 mM Polyethyleneglycol (PEG) stressed leaves of Hevea
      brasiliensis by RACE. The HbMT2a was 372bp in length and had a 237bp open reading
      frame (ORF) encoding for a protein of 78 amino acid residues with molecular mass
      of 7.772 kDa. The expression of HbMT2a in the detached leaves of rubber tree
      clone RY7-33-97 was up-regulated by Me-JA, ABA, PEG, H2O2, Cu(2+) and Zn(2+), but
      down-regulated by water. The role of HbMT2a protein in protecting against metal
      toxicity was demonstrated in vitro. PET-28a-HbMT2-beared Escherichia coli.
      Differential expression of HbMT2a upon treatment with 10  degrees C was observed
      in the detached leaves of rubber tree clone 93-114 which is cold-resistant and
      Reken501 which is cold-sensitive. The expression patterns of HbMT2a in the two
      rubber tree clones may be ascribed to a change in the level of endogenous H2O2. 

PMID- 25858316
TI  - IL32gamma activates natural killer receptor-expressing innate immune cells to
      produce IFNgamma via dendritic cell-derived IL12.
AB  - The inflammatory cytokine IL32gamma acts on dendritic cells (DCs) to produce IL12
      and IL6, which are involved in the differentiation of Th1 and Th17 cells. Natural
      killer (NK) and NKT cells play important roles in IL12-mediated adaptive immune
      responses, such as antitumor immunity. Herein we demonstrate the effect of
      IL32gamma on the activation of NK and NKT cells. Upon IL32gamma stimulation,
      splenic NK and NKT cells could be activated, and this activation was dependent on
      both IL12 and DCs, which was confirmed by using IL12p35 knockout and CD11c
      diphtheria toxin receptor transgenic mouse models. Furthermore, IL32gamma could
      induce the production of proinflammatory cytokines by NKDCs, a subset of DCs
      expressing NK cell markers, known to enhance NKT cell function. Unlike
      conventional DCs, NKDCs produced IFNgamma and TNFalpha rather than IL12 upon
      stimulation with IL32gamma. Taken together, IL32gamma will be useful as an
      adjuvant to boost the cytotoxicities of NK and NKT cells that play critical roles
      in antitumor immunity. 

PMID- 25858317
TI  - Amiloride-insensitive sodium channels are directly regulated by actin
      cytoskeleton dynamics in human lymphoma cells.
AB  - Sodium influx mediated by ion channels of plasma membrane underlies fundamental
      physiological processes in cells of blood origin. However, little is known about
      the single channel activity and regulatory mechanisms of sodium-specific channels
      in native cells. In the present work, we used different modes of patch clamp
      technique to examine ion channels involved in Na-transporting pathway in U937
      human lymphoma cells. The activity of native non-voltage-gated sodium (NVGS)
      channels with unitary conductance of 10 pS was revealed in cell-attached, inside
      out and whole-cell configurations. NVGS channel activity is directly controlled
      by submembranous actin cytoskeleton. Specifically, an activation of sodium
      channels in U937 cells in response to microfilament disassembly was demonstrated
      on single-channel and integral current level. Inside-out experiments showed that
      filament assembly on cytoplasmic membrane surface caused fast inactivation of the
      channels. Biophysical characteristics of NVGS channels in U937 cells were similar
      to that of epithelial sodium channels (ENaCs). However, we found that amiloride,
      a known inhibitor of DEG/ENaC, did not block NVGS channels in U937 cells. Whole
      cell current measurements revealed no amiloride-sensitive component of membrane
      current. Our data show that cortical actin structures represent the main factor
      that controls the activity of amiloride-insensitive ENaC-like channels in human
      lymphoma cells. 

PMID- 25858318
TI  - EGFR-independent autophagy induction with gefitinib and enhancement of its
      cytotoxic effect by targeting autophagy with clarithromycin in non-small cell
      lung cancer cells.
AB  - Gefitinib (GEF), an inhibitor for EGFR tyrosine kinase, potently induces
      autophagy in non-small cell lung cancer (NSCLC) cell lines such as PC-9 cells
      expressing constitutively activated EGFR kinase by EGFR gene mutation as well as
      A549 and H226 cells with wild-type EGFR. Unexpectedly, GEF-induced autophagy was
      also observed in non-NSCLC cells such as murine embryonic fibroblasts (MEF) and
      leukemia cell lines K562 and HL-60 without EGFR expression. Knockout of EGFR gene
      in A549 cells by CRISPR/Cas9 system still exhibited autophagy induction after
      treatment with GEF, indicating that the autophagy induction by GEF is not
      mediated through inhibiting EGFR kinase activity. Combined treatment with GEF and
      clarithromycin (CAM), a macrolide antibiotic having the effect of inhibiting
      autophagy flux, enhances the cytotoxic effect in NSCLC cell lines, although
      treatment with CAM alone exhibits no cytotoxicity. GEF treatment induced up
      regulation of endoplasmic reticulum (ER)-stress related genes such as
      CHOP/GADD153 and GRP78. Knockdown of CHOP in PC-9 cells and Chop-knockout MEF
      both exhibited less sensitivity to GEF than controls. Addition of CAM in culture
      medium resulted in further pronounced GEF-induced ER stress loading, while CAM
      alone exhibited no effect. These data suggest that GEF-induced autophagy
      functions as cytoprotective and indicates the potential therapeutic possibility
      of using CAM for GEF therapy. Furthermore, it is suggested that the intracellular
      signaling for autophagy initiation in response to GEF can be completely
      dissociated from EGFR, but unknown target molecule(s) of GEF for autophagy
      induction might exist. 

PMID- 25858319
TI  - Structural basis for the substrate selectivity of a HAD phosphatase from
      Thermococcus onnurineus NA1.
AB  - Proteins in the haloalkaloic acid dehalogenase (HAD) superfamily, which is one of
      the largest enzyme families, is generally composed of a catalytic core domain and
      a cap domain. Although proteins in this family show broad substrate
      specificities, the mechanisms of their substrate recognition are not well
      understood. In this study, we identified a new substrate binding motif of HAD
      proteins from structural and functional analyses, and propose that this motif
      might be crucial for interacting with hydrophobic rings of substrates. The
      crystal structure of TON_0338, one of the 17 putative HAD proteins identified in
      a hyperthermophilic archaeon, Thermococcus onnurineus NA1, was determined as an
      apo-form at 2.0 A resolution. In addition, we determined the crystal structure
      TON_0338 in complex with Mg(2+) or N-cyclohexyl-2-aminoethanesulfonic acid (CHES)
      at 1.7 A resolution. Examination of the apo-form and CHES-bound structures
      revealed that CHES is sandwiched between Trp58 and Trp61, suggesting that this
      Trp sandwich might function as a substrate recognition motif. In the phosphatase
      assay, TON_0338 was shown to have high activity for flavin mononucleotide (FMN),
      and the docking analysis suggested that the flavin of FMN may interact with Trp58
      and Trp61 in a way similar to that observed in the crystal structure. Moreover,
      the replacement of these tryptophan residues significantly reduced the
      phosphatase activity for FMN. Our results suggest that WxxW may function as a
      substrate binding motif in HAD proteins, and expand the diversity of their
      substrate recognition mode. 

PMID- 25858320
TI  - Sir2 is involved in the transcriptional modulation of NHP6A in Saccharomyces
      cerevisiae.
AB  - The Sir proteins, namely Sir2, 3 and 4, have roles related to heterochromatin,
      but genome-wide studies have revealed their presence at many euchromatic loci,
      although the functional meaning of this is still not clear. Nhp6a is an abundant
      HMG-like protein in yeast, which has a role in transcription by modulating
      chromatin structure and nucleosome number. Although much is known about its
      structure and function, information regarding its regulation is scarce. NHP6A,
      among other genes, emerges in ChIP-on chip studies of global Sir proteins
      binding, suggesting it could be regulated by SIR. We have investigated NHP6A
      expression in sir deletion mutants as well as in SIR2 overexpressing conditions.
      In addition, we have asked if the Sir2 deacetylation activity is involved by
      using conditions that either inhibit (treatment with nicotinamide) or enhance
      (calorie restriction conditions) Sir2 activity. We have found that, consistent
      with previous microarray studies, NHP6A expression undergoes a slight increase in
      sir mutant strains, but is strongly repressed when SIR2 is overexpressed. In a
      sir3 mutant strain the gene continues to be transcribed, even in SIR2
      overexpressing conditions. In addition, treating the cells with nicotinamide
      counteracts the SIR2 overexpressing effect. Finally, conditions that are known to
      potentiate Sir2 deacetylation activity seem to mimic the effect of SIR2
      overexpression on NHP6A. Our results suggest that Sir2 is involved in the
      regulation of NHP6A promoter, acting more as a specific repressor, rather than a
      long-range silencer. This effect is specific, and the Sir2 deacetylase activity
      is required for the Sir2 mediated repression of NHP6A. Moreover, the presence of
      the SIR complex seems required for Sir2 to silence NHP6A. 

PMID- 25858321
TI  - Downregulation of the DNA repair enzyme apurinic/apyrimidinic endonuclease 1
      stimulates transforming growth factor-beta1 production and promotes actin
      rearrangement.
AB  - The DNA repair enzyme apurinic/apyrimidinic endonuclease 1 (APE1) plays a central
      role in base excision repair and functions as a reductive activator of various
      transcription factors. Multiple other functionalities have been ascribed to APE1
      in addition to these major functions. A recent study showed that APE1 knockdown
      upregulated the expression of a set of genes related to extracellular matrix
      (ECM) production, indicating an additional novel biological role for this enzyme.
      Based on this finding, we have investigated the effect of APE1 downregulation on
      ECM-related gene expression and its biological consequences. Endogenous APE1
      expression was downregulated in human cervical carcinoma HeLa cells and human
      lung carcinoma A549 cells using siRNA. When the expression of six ECM-related
      genes (TGFB1, LAMC1, FN1, COL1A1, COL3A1, and COL4A1) was evaluated, we found
      that APE1 knockdown upregulated the expression of TGFB1 in both cell lines. APE1
      downregulation promoted actin rearrangement, inducing F-actin accumulation in
      HeLa cells and the dissipation of stress fibers in A549 cells. We also discovered
      that APE1 knockdown enhanced cellular motility in A549 cells, which was
      suppressed by the inhibition of transforming growth factor (TGF)-beta1 signaling.
      These results suggested that APE1 controls the organization of actin cytoskeleton
      through the regulation of TGF-beta1 expression, providing novel insights into the
      biological significance of APE1. 

PMID- 25858322
TI  - Molecular imaging of inflammation in the ApoE -/- mouse model of atherosclerosis
      with IodoDPA.
AB  - BACKGROUND: Atherosclerosis is a common and serious vascular disease predisposing
      individuals to myocardial infarction and stroke. Intravascular plaques, the
      pathologic lesions of atherosclerosis, are largely composed of cholesterol-laden
      luminal macrophage-rich infiltrates within a fibrous cap. The ability to detect
      those macrophages non-invasively within the aorta, carotid artery and other
      vessels would allow physicians to determine plaque burden, aiding management of
      patients with atherosclerosis. METHODS AND RESULTS: We previously developed a low
      molecular-weight imaging agent, [(125)I]iodo-DPA-713 (iodoDPA), which selectively
      targets macrophages. Here we use it to detect both intravascular macrophages and
      macrophage infiltrates within the myocardium in the ApoE -/- mouse model of
      atherosclerosis using single photon emission computed tomography (SPECT). SPECT
      data were confirmed by echocardiography, near-infrared fluorescence imaging and
      histology. SPECT images showed focal uptake of radiotracer at the aortic root in
      all ApoE -/- mice, while the age-matched controls were nearly devoid of
      radiotracer uptake. Focal radiotracer uptake along the descending aorta and
      within the myocardium was also observed in affected animals. CONCLUSIONS: IodoDPA
      is a promising new imaging agent for atherosclerosis, with specificity for the
      macrophage component of the lesions involved.

PMID- 25858323
TI  - Enhanced expression of the beta4-N-acetylgalactosaminyltransferase 4 gene impairs
      tumor growth of human breast cancer cells.
AB  - Two beta4-N-acetylgalactosaminyltransferases (beta4GalNAcTs), beta4GalNAcT3 and
      beta4GalNAcT4, have been shown to be involved in the synthesis of the GalNAcbeta1
      -> 4GlcNAc (LacdiNAc) group expressed on the outer branches of N- and/or O
      glycans, and only beta4GalNAcT4 is expressed in human mammary gland. We found
      that the expression level of the LacdiNAc group decreases as human breast cancers
      progress. To investigate biological significances of this disaccharide in human
      breast cancers, we transfected the FLAG-tagged beta4GalNAcT4 cDNA into MDA-MB-231
      cells, and obtained several clones showing enhanced expression of the gene.
      Clones 1 and 2 showed 15 and 9 times more transcript than mock-transfected cells.
      The FLAG-beta4GalNAcT4 protein and its product, the LacdiNAc group, were detected
      in clone 1 and 2 cells. No change was observed in their growth rates while
      significant decreases in colony forming and invasive abilities were observed for
      clone 1 and 2 cells. When clone 1 cells were transplanted subcutaneously into
      nude mice, no tumors were formed while tumors were formed with mock-transfected
      cells. These results indicate that the expression of the LacdiNAc group is quite
      important for the suppression of malignancies of the MDA-MB-231 cells. 

PMID- 25858324
TI  - Stomatal density and aperture in non-vascular land plants are non-responsive to
      above-ambient atmospheric CO2 concentrations.
AB  - BACKGROUND AND AIMS: Following the consensus view for unitary origin and
      conserved function of stomata across over 400 million years of land plant
      evolution, stomatal abundance has been widely used to reconstruct palaeo
      atmospheric environments. However, the responsiveness of stomata in mosses and
      hornworts, the most basal stomate lineages of extant land plants, has received
      relatively little attention. This study aimed to redress this imbalance and
      provide the first direct evidence of bryophyte stomatal responsiveness to
      atmospheric CO2. METHODS: A selection of hornwort (Anthoceros punctatus,
      Phaeoceros laevis) and moss (Polytrichum juniperinum, Mnium hornum, Funaria
      hygrometrica) sporophytes with contrasting stomatal morphologies were grown under
      different atmospheric CO2 concentrations ([CO2]) representing both modern (440
      p.p.m. CO2) and ancient (1500 p.p.m. CO2) atmospheres. Upon sporophyte
      maturation, stomata from each bryophyte species were imaged, measured and
      quantified. KEY RESULTS: Densities and dimensions were unaffected by changes in
      [CO2], other than a slight increase in stomatal density in Funaria and
      abnormalities in Polytrichum stomata under elevated [CO2]. CONCLUSIONS: The
      changes to stomata in Funaria and Polytrichum are attributed to differential
      growth of the sporophytes rather than stomata-specific responses. The absence of
      responses to changes in [CO2] in bryophytes is in line with findings previously
      reported in other early lineages of vascular plants. These findings strengthen
      the hypothesis of an incremental acquisition of stomatal regulatory processes
      through land plant evolution and urge considerable caution in using stomatal
      densities as proxies for paleo-atmospheric CO2 concentrations.

PMID- 25858326
TI  - Pure duplication of 19p13.3 in three members of a family with intellectual
      disability and literature review. Definition of a new microduplication syndrome.
AB  - This paper describes the presence of an interstitial pure duplication of 19p13.3
      (4.95 Mb) in a patient with intellectual disability studied by array-CGH which
      was initially considered as a de novo alteration. The discovery of the same
      chromosomal alteration in a first-degree cousin of this patient led us to
      investigate the presence of insertional translocations, which were consequently
      found in three family generations. The same duplication was found in three
      intellectually disabled patients and among the translocation carrier family
      members a very high incidence of miscarriages are reported. A review of other
      published cases has allowed us to find three other patients with a similar pure
      duplication, all of them sharing some common clinical findings such as
      intrauterine growth retardation, microcephaly, motor and speech delay, moderate
      to severe intellectual disability, and dysmorphic features. These findings allow
      us to suggest the presence of a new microduplication syndrome in chromosomal
      region 19p13.3.

PMID- 25858327
TI  - The growth and medicinal quality of Epimedium wushanense are improved by an
      isolate of dark septate fungus.
AB  - CONTEXT: Seven dark-septate endophytic (DSE) fungi have been isolated from the
      roots of Epimedium wushanense T. S. Ying (Berberidaceae), an important medicinal
      plant with various pharmacological activities. OBJECTIVE: The current study
      explores the effects of seven DSE fungi on the growth and accumulation of
      bioactive compounds in E. wushanense. MATERIALS AND METHODS: Each 1-month-old E.
      wushanense seedling was inoculated with one of the seven DSE fungi and was grown
      under greenhouse conditions for 90 d. The molecular identification of the fungi
      was based on the ITS1-5.8S-ITS2 nuclear ribosomal gene cluster. RESULTS: The
      results showed that the influence of DSE fungi inoculation varied between
      strains. Inoculation with DSE8 not only significantly enhanced plant height, root
      length, leaf area, leaf number, and shoot and root biomass but also improved the
      total flavonoid and icariin content, with an increase ranging from 20.24% to
      237.97%. Three of the seven DSE fungi caused the inoculated plants to die, and
      the remaining three DSE strains showed neutral or negative effects on plant
      growth and the accumulation of bioactive compounds. According to the ITS
      sequence, DSE8 is congeneric to the genus Leptodontidium. DISCUSSION AND
      CONCLUSION: The findings indicate that application of DSE8 may be valuable to
      facilitate the cultivation of E. wushanense with a higher biomass and improved
      medicinal quality.

PMID- 25858325
TI  - Transcript profiles in cortical cells of maize primary root during ethylene
      induced lysigenous aerenchyma formation under aerobic conditions.
AB  - BACKGROUND AND AIMS: Internal aeration is important for plants to survive during
      periods of waterlogging, and the ability to form aerenchyma contributes by
      creating a continuous gas space between the shoots and the roots. Roots of maize
      (Zea mays) react to prolonged waterlogging by forming aerenchyma in root cortical
      cells by programmed cell death (PCD) in response to ethylene. The aim of this
      study was to understand the molecular mechanisms of ethylene-induced aerenchyma
      formation by identifying genes that are either up- or downregulated by ethylene
      treatment in maize root cortical cells. METHODS: Three-day-old maize seedlings
      were treated with ethylene for several hours under aerobic conditions. Cortical
      cells were isolated from the primary roots using laser microdissection (LM), and
      transcript profiles with and without ethylene treatment were compared by
      microarray. In addition, the effect on ethylene-induced aerenchyma formation of
      diphenyleneiodonium (DPI), an inhibitor of NADPH oxidases, was examined in order
      to assess the involvement of reactive oxygen species (ROS). KEY RESULTS: A total
      of 223 genes were identified whose transcript levels were significantly increased
      or decreased by ethylene treatment in root cortical cells under aerobic
      conditions. Subsequent tissue-specific quantitative reverse-transcription PCR
      analyses revealed that ethylene increased the transcript levels of genes related
      to ethylene signalling in all of the root tissues examined (stelar cells,
      cortical cells and outer cell layers), whereas it increased the transcript levels
      of genes related to cell wall modification and proteolysis specifically in the
      cortical cells. DPI treatment inhibited the ethylene-induced aerenchyma formation
      and suppressed expression of some cell wall modification-related genes.
      CONCLUSIONS: Several genes related to cell wall modification and proteolysis are
      specifically up- or downregulated in cortical cells during lysigenous aerenchyma
      formation under aerobic conditions with ethylene treatment. The results suggest
      that ethylene is perceived in stelar cells, cortical cells and outer cell layers
      in the maize primary root, and that the cortical cell-specific PCD is controlled
      downstream of ethylene perception through subsequent gene expression, which is
      partly regulated by ROS, in the cortical cells.

PMID- 25858328
TI  - Estimation of the cutoff value of vitamin D: the Dong-gu study.
AB  - BACKGROUND: Vitamin D plays an essential role in bone health and growth, but the
      optimal serum 25-hydroxyvitamin D (25(OH)D) concentration is not known. This
      study was performed to investigate the optimal 25(OH)D concentration in regard to
      parathyroid hormone (PTH) concentration in the Korean general population aged 50
      years or older. FINDINGS: The study population consisted of 8,857 subjects (3,545
      men and 5,312 women) who participated in the baseline survey of the Dong-gu
      study, conducted in Korea between 2007 and 2010. Serum 25(OH)D and PTH
      concentrations were measured by chemiluminescent microparticle immunoassay. The
      optimal 25(OH)D concentration was estimated by using nonlinear regression model.
      Our data show that PTH concentration reached a theoretical plateau at 38.2 pg/ml
      and corresponding 25(OH)D concentration was 21.1 ng/ml in men and PTH
      concentration at 42.9 pg/ml and 25(OH)D concentration at 13.8 ng/ml in women.
      CONCLUSIONS: These results indicate that, for Korean general population aged 50
      years or older, the optimal 25(OH)D concentration is 21.1 ng/ml in men and 13.8
      ng/ml in women.

PMID- 25858330
TI  - Carrier transport in quantum dot quantum well microstructures of the self
      assembled CdTe/CdS/ligand core-shell system.
AB  - The study on the quantum dot quantum well (QDQW) microstructure modified by
      choosing different ligands containing a sulfhydryl group is of significance
      because it enables one to regulate photoexcited free charge carriers' (FCCs')
      transport behaviours in high-quality CdTe/ligand QDs via a self-assembled way.
      The photoelectron characteristics of ligand-capped CdTe nanoparticles were probed
      by a combination of surface photovoltaic (SPV) and photoacoustic technologies,
      supplemented by a computer simulation method of the CASTEP module. The experiment
      reveals that the D-value DeltaEWi obtained by the associated two parameters of
      the SPV spectroscopy was closely related to the quantum confinement energy in the
      self-assembled CdTe/CdS/ligand core-shell system. In the paper the D-value was
      termed the depth of QWs, which were buried in the space charge regions located in
      the graded-band-gap and on either side of the shell-CdS. Obvious resonance
      quantum tunnelling may occur in the energy band structure with deep QWs on using
      certain ligands, resulting in an extended diffusion length of the FCCs on
      illumination of the photon energy hnu >= Eg, core-CdTe, and in a strong SPV
      response at a specific wavelength region. In addition, the carrier-longitudinal
      optical phonon interaction is the reciprocal of the carriers' lifetime. The d
      frontier orbital in the graded-band-gap plays an important role in both the
      microstructure and the resonance quantum tunnelling of the QDQW system according
      to the CASTEP calculations. 

PMID- 25858331
TI  - "Bleeding in the jungle".

PMID- 25858332
TI  - Risk Factors, Warning Signs, and Drivers of Suicide: What Are They, How Do They
      Differ, and Why Does It Matter?
AB  - Research investigating suicide attempts and deaths by suicide has yielded many
      specific risk factors and warning signs for future suicidal behaviors. Yet, even
      though these variables are each valuable for suicide prevention efforts, they may
      be limited in their applicability to clinical practice. The differences among
      risk factors, warning signs, and "drivers," which are person-specific variables
      that lead individuals to desire death by suicide, are highlighted. The scarce
      evidence on drivers is described and specific recommendations for conducting
      future drivers-focused research and targeting them in clinical practice are
      suggested. 

PMID- 25858333
TI  - Clinical effectiveness and cost-effectiveness of foam sclerotherapy, endovenous
      laser ablation and surgery for varicose veins: results from the Comparison of
      LAser, Surgery and foam Sclerotherapy (CLASS) randomised controlled trial.
AB  - BACKGROUND: Foam sclerotherapy (foam) and endovenous laser ablation (EVLA) have
      emerged as alternative treatments to surgery for patients with varicose veins,
      but uncertainty exists regarding their effectiveness in the medium to longer
      term. OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of
      foam, EVLA and surgery for the treatment of varicose veins. DESIGN: A parallel
      group randomised controlled trial (RCT) without blinding, and economic modelling
      evaluation. SETTING: Eleven UK specialist vascular centres. PARTICIPANTS: Seven
      hundred and ninety-eight patients with primary varicose veins (foam, n = 292;
      surgery, n = 294; EVLA, n = 212). INTERVENTIONS: Patients were randomised between
      all three treatment options (eight centres) or between foam and surgery (three
      centres). PRIMARY OUTCOME MEASURES: Disease-specific [Aberdeen Varicose Vein
      Questionnaire (AVVQ)] and generic [European Quality of Life-5 Dimensions (EQ-5D),
      Short Form questionnaire-36 items (SF-36) physical and mental component scores]
      quality of life (QoL) at 6 months. Cost-effectiveness as cost per quality
      adjusted life-year (QALY) gained. SECONDARY OUTCOME MEASURES: Quality of life at
      6 weeks; residual varicose veins; Venous Clinical Severity Score (VCSS);
      complication rates; return to normal activity; truncal vein ablation rates; and
      costs. RESULTS: The results appear generalisable in that participants' baseline
      characteristics (apart from a lower-than-expected proportion of females) and post
      treatment improvement in outcomes were comparable with those in other RCTs. The
      health gain achieved in the AVVQ with foam was significantly lower than with
      surgery at 6 months [effect size -1.74, 95% confidence interval (CI) -2.97 to 
      0.50; p = 0.006], but was similar to that achieved with EVLA. The health gain in
      SF-36 mental component score for foam was worse than that for EVLA (effect size
      1.54, 95% CI 0.01 to 3.06; p = 0.048) but similar to that for surgery. There were
      no differences in EQ-5D or SF-36 component scores in the surgery versus foam or
      surgery versus EVLA comparisons at 6 months. The trial-based cost-effectiveness
      analysis showed that, at 6 months, foam had the highest probability of being
      considered cost-effective at a ceiling willingness-to-pay ratio of L20,000 per
      QALY. EVLA was found to cost L26,107 per QALY gained versus foam, and was less
      costly and generated slightly more QALYs than surgery. Markov modelling using
      trial costs and the limited recurrence data available suggested that, at 5 years,
      EVLA had the highest probability (~ 79%) of being cost-effective at conventional
      thresholds, followed by foam (~ 17%) and surgery (~ 5%). With regard to secondary
      outcomes, health gains at 6 weeks (p < 0.005) were greater for EVLA than for foam
      (EQ-5D, p = 0.004). There were fewer procedural complications in the EVLA group
      (1%) than after foam (7%) and surgery (8%) (p < 0.001). Participants returned to
      a wide range of behaviours more quickly following foam or EVLA than following
      surgery (p < 0.05). There were no differences in VCSS between the three
      treatments. Truncal ablation rates were higher for surgery (p < 0.001) and EVLA
      (p < 0.001) than for foam, and were similar for surgery and EVLA. CONCLUSIONS:
      Considerations of both the 6-month clinical outcomes and the estimated 5-year
      cost-effectiveness suggest that EVLA should be considered as the treatment of
      choice for suitable patients. FUTURE WORK: Five-year trial results are currently
      being evaluated to compare the cost-effectiveness of foam, surgery and EVLA, and
      to determine the recurrence rates following each treatment. This trial has
      highlighted the need for long-term outcome data from RCTs on QoL, recurrence
      rates and costs for foam sclerotherapy and other endovenous techniques compared
      against each other and against surgery. TRIAL REGISTRATION: Current Controlled
      Trials ISRCTN51995477. FUNDING: This project was funded by the National Institute
      for Health Research (NIHR) Health Technology Assessment programme and will be
      published in full in Health Technology Assessment; Vol. 19, No. 27. See the NIHR
      Journals Library website for further project information.

PMID- 25858334
TI  - Declines in migrant shorebird populations from a winter-quarter perspective.
AB  - Many long-distance migrating shorebird (i.e., sandpipers, plovers, flamingos,
      oystercatchers) populations are declining. Although regular shorebird monitoring
      programs exist worldwide, most estimates of shorebird population trends and sizes
      are poor or nonexistent. We built a state-space model to estimate shorebird
      population trends. Compared with more commonly used methods of trend estimation,
      state-space models are more mechanistic, allow for the separation of observation
      and state process, and can easily accommodate multivariate time series and
      nonlinear trends. We fitted the model to count data collected from 1990 to 2013
      on 18 common shorebirds at the 2 largest coastal wetlands in southern Africa,
      Sandwich Harbour (a relatively pristine bay) and Walvis Bay (an international
      harbor), Namibia. Four of the 12 long-distance migrant species declined since
      1990: Ruddy Turnstone (Arenaria interpres), Little Stint (Calidris minuta),
      Common Ringed Plover (Charadrius hiaticula), and Red Knot (Calidris canutus).
      Populations of resident species and short-distance migrants increased or were
      stable. Similar patterns at a key South African wetland suggest that shorebird
      populations migrating to southern Africa are declining in line with the global
      decline, but local conditions in southern Africa's largest wetlands are not
      contributing to these declines. State-space models provide estimates of
      population levels and trends and could be used widely to improve the current
      state of water bird estimates.

PMID- 25858335
TI  - Bullous skin lesions in an adult male: a diagnostic dilemma.
AB  - BACKGROUND: Henoch-Schonlein Purpura (HSP) is an IgA small-vessel vasculitis that
      is primarily a disease of childhood. Its presentation in adulthood is rare and
      has a more severe disease course. We present a case with an atypical presentation
      of this disease that was a diagnostic challenge for multiple providers. CASE
      REPORT: A 42-year-old man noticed bullous lesions over his ankles that spread to
      his entire legs over a few weeks. They later became necrotic and ulcerated areas.
      His primary care physician and 2 dermatologists could not reach a definitive
      diagnosis. He then presented to our hospital with new abdominal pain, rectal
      bleeding, and a new elevation in liver enzymes. A biopsy of his skin lesions led
      to the diagnosis of HSP. CONCLUSIONS: We discuss this highly unusual initial
      presentation with bullous skin lesions and liver enzyme abnormalities and explore
      the medical literature to understand its pathogenesis. Clinicians need to be
      aware of this rare presentation to avoid a delay in diagnosis and management.

PMID- 25858336
TI  - Polypharmacy and frailty: prevalence, relationship, and impact on mortality in a
      French sample of 2350 old people.
AB  - PURPOSE: To assess the prevalence of polypharmacy and frailty, to examine their
      association, and to establish their independent and combined effects on mortality
      in a sample of French old people. METHODS: This is a cross-sectional population
      study of people aged 70 years and over. A total of 2350 respondents were
      interviewed at home in 2008-2010. Frailty was defined as impairment in three
      domains or more among nutrition, energy, physical activity, strength, and
      mobility, in the absence of difficulties in basic activities of daily living.
      Mortality data were documented after a mean follow-up period of 2.6 years.
      RESULTS: Mean age of the population was 83.3 +/- 7.5 years, with 59.4% of women.
      Prevalence of frailty was 17.0%. Polypharmacy (5-9 drugs) was reported in 53.6%
      of the population, and excessive polypharmacy (10 drugs or more) in 13.8%. After
      adjustment for socio-demographic and health variables, polypharmacy and excessive
      polypharmacy were associated with frailty with odds ratio 1.77 [1.20-2.61] and
      4.47 [2.37-8.42], respectively. Frailty (hazard ratio [HR] 2.56 [1.63-4.04]) and
      excessive polypharmacy (HR 1.83 [1.28-2.62]) were independent predictors of
      mortality. Compared with non-frail people without polypharmacy, frail people with
      excessive polypharmacy were six times more likely to die during the follow-up
      period (HR 6.30 [3.09-12.84]). CONCLUSION: By showing the independent and
      combined effects of polypharmacy and frailty on mortality risk, this study should
      reinforce the awareness of clinicians with regard to these factors, rather
      prevalent in old people.

PMID- 25858337
TI  - Jaw-muscle architecture and mandibular morphology influence relative maximum jaw
      gapes in the sexually dimorphic Macaca fascicularis.
AB  - Maximum jaw gape is a performance variable related to feeding and non-feeding
      oral behaviors, such as canine gape displays, and is influenced by several
      factors including jaw-muscle fiber architecture, muscle position on the skull,
      and jaw morphology. Maximum gape, jaw length, and canine height are strongly
      correlated across catarrhine primates, but relationships between gape and other
      aspects of masticatory apparatus morphology are less clear. We examine the
      effects of jaw-adductor fiber architecture, jaw-muscle leverage, and jaw form on
      gape in an intraspecific sample of sexually dimorphic crab-eating macaques
      (Macaca fascicularis). As M. fascicularis males have relatively larger maximum
      gapes than females, we predict that males will have muscle and jaw morphologies
      that facilitate large gape, but these morphologies may come at some expense to
      bite force. Male crab-eating macaques have relatively longer jaw-muscle fibers,
      masseters with decreased leverage, and temporomandibular joint morphologies that
      facilitate the production of wide gapes. Because relative canine height is
      correlated with maximum gape in catarrhines, and males have relatively longer
      canines than females, these results support the hypothesis that male M.
      fascicularis have experienced selection to increase maximum gape. The sexes do
      not differ in relative masseter physiologic cross-sectional area (PCSA), but
      males compensate for a potential trade-off between muscle excursion versus muscle
      force with increased temporalis weight and PCSA. This musculoskeletal
      configuration is likely functionally significant for behaviors involving
      aggressive canine biting and displays in male M. fascicularis and provides
      additional evidence supporting the multifactorial nature of the catarrhine
      masticatory apparatus. Our results have implications for the evolution of
      craniofacial morphology in catarrhine primates and reinforce the importance of
      evaluating additional factors other than feeding behavior and diet in analyses of
      masticatory apparatus form, function, and evolution. 

PMID- 25858338
TI  - A gardener with a Fever for 2 weeks.

PMID- 25858339
TI  - Ophthalmic Artery Occlusion after Cocaine Use.

PMID- 25858340
TI  - Comments on: "Toxicity of Antihypertensives in Unintentional Poisoning of Young
      Children".

PMID- 25858341
TI  - Jejunojejunal Intussusception.

PMID- 25858342
TI  - Dislodged pacer lead causing ventricular tachycardia.

PMID- 25858343
TI  - Reversible Cerebral Vasoconstriction Syndrome.
AB  - BACKGROUND: Reversible cerebral vasoconstriction syndrome (RCVS) is an
      underappreciated and poorly understood cause of thunderclap headache (TCH).
      Although self-limited in the majority of patients, incidence is increasing, with
      presentations overlapping considerably with life-threatening conditions, such as
      aneurysmal subarachnoid hemorrhage and stroke. In addition, radiographic findings
      seen in RCVS are also present in primary angiitis of the central nervous system
      (PACNS). Misdiagnosis of RCVS might subject patients to unnecessary invasive
      testing and immunosuppressive therapy. Furthermore, the recommended treatment of
      glucocorticoids used in PACNS can be harmful in RCVS. RCVS is not a benign
      condition, as patients can have ischemic or hemorrhagic complications leading to
      persistent neurologic deficits and even death. Current treatments, guided only by
      expert consensus, have no proven effect on these complications, which argues the
      need for accurate identification of patients with RCVS and prospective studies to
      validate treatment and inform prognoses. CASE REPORT: We describe a previously
      healthy male who presented to the emergency department after 2 episodes of TCH
      and angiography consistent with RCVS. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE
      OF THIS?: RCVS is a common but underappreciated cause of TCH. The likelihood of
      misdiagnosing RCVS following the accepted diagnostic algorithm of acute headache
      in the emergency department is high due to a lack of clinical awareness and
      common features shared with other headache syndromes. Emergency department
      physicians must broaden the differential in patients presenting to the emergency
      department with TCH to include RCVS and be familiar with the accepted treatments
      and appropriate follow-up.

PMID- 25858344
TI  - Phenolic profile within the fine-root branching orders of an evergreen species
      highlights a disconnect in root tissue quality predicted by elemental- and
      molecular-level carbon composition.
AB  - Fine roots constitute a significant source of plant productivity and litter
      turnover across terrestrial ecosystems, but less is known about the quantitative
      and qualitative profile of phenolic compounds within the fine-root architecture,
      which could regulate the potential contribution of plant roots to the soil
      organic matter pool. To understand the linkage between traditional macro
      elemental and morphological traits of roots and their molecular-level carbon
      chemistry, we analyzed seasonal variations in monomeric yields of the free,
      bound, and lignin phenols in fine roots (distal five orders) and leaves of
      Ardisia quinquegona. Fine roots contained two-fold higher concentrations of bound
      phenols and three-fold higher concentrations of lignin phenols than leaves.
      Within fine roots, the concentrations of free and bound phenols decreased with
      increasing root order, and seasonal variation in the phenolic profile was more
      evident in lower order than in higher order roots. The morphological and macro
      elemental root traits were decoupled from the quantity, composition and tissue
      association of phenolic compounds, revealing the potential inability of these
      traditional parameters to capture the molecular identity of phenolic carbon
      within the fine-root architecture and between fine roots and leaves. Our results
      highlight the molecular-level heterogeneity in phenolic carbon composition within
      the fine-root architecture, and imply that traits that capture the molecular
      identity of the root construct might better predict the decomposition dynamics
      within fine-root orders.

PMID- 25858345
TI  - Rivastigmine for Alzheimer's disease.
AB  - BACKGROUND: Alzheimer's disease is the commonest cause of dementia affecting
      older people. One of the therapeutic strategies aimed at ameliorating the
      clinical manifestations of Alzheimer's disease is to enhance cholinergic
      neurotransmission in the brain by the use of cholinesterase inhibitors to delay
      the breakdown of acetylcholine released into synaptic clefts. Tacrine, the first
      of the cholinesterase inhibitors to undergo extensive trials for this purpose,
      was associated with significant adverse effects including hepatotoxicity. Other
      cholinesterase inhibitors, including rivastigmine, with superior properties in
      terms of specificity of action and lower risk of adverse effects have since been
      introduced. Rivastigmine has received approval for use in 60 countries including
      all member states of the European Union and the USA. OBJECTIVES: To determine the
      clinical efficacy and safety of rivastigmine for patients with dementia of
      Alzheimer's type. SEARCH METHODS: We searched ALOIS, the Cochrane Dementia and
      Cognitive Improvement Group Specialized Register, on 2 March 2015 using the
      terms: Rivastigmine OR  exelon OR ENA OR "SDZ ENA 713". ALOIS contains records of
      clinical trials identified from monthly searches of a number of major healthcare
      databases (Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS), numerous
      trial registries and grey literature sources. SELECTION CRITERIA: We included all
      unconfounded, double-blind, randomised, controlled trials in which treatment with
      rivastigmine was administered to patients with dementia of the Alzheimer's type
      for 12 weeks or more and its effects compared with those of placebo in a parallel
      group of patients, or where two formulations of rivastigmine were compared. DATA
      COLLECTION AND ANALYSIS: One review author (JSB) applied the study selection
      criteria, assessed the quality of studies and extracted data. MAIN RESULTS: A
      total of 13 trials met the inclusion criteria of the review. The trials had a
      duration of between 12 and 52 weeks. The older trials tested a capsule form with
      a dose of up to 12 mg/day. Trials reported since 2007 have tested continuous dose
      transdermal patch formulations delivering 4.6, 9.5 and 17.7 mg/day.Our main
      analysis compared the safety and efficacy of rivastigmine 6 to 12 mg/day orally
      or 9.5 mg/day transdermally with placebo.Seven trials contributed data from 3450
      patients to this analysis. Data from another two studies were not included
      because of a lack of information and methodological concerns. All the included
      trials were multicentre trials and recruited patients with mild to moderate
      Alzheimer's disease with a mean age of about 75 years. All had low risk of bias
      for randomisation and allocation but the risk of bias due to attrition was
      unclear in four studies, low in one study and high in two studies.After 26 weeks
      of treatment rivastigmine compared to placebo was associated with better outcomes
      for cognitive function measured with the Alzheimer's Disease Assessment Scale
      Cognitive (ADAS-Cog) score (mean difference (MD) -1.79; 95% confidence interval
      (CI) -2.21 to -1.37, n = 3232, 6 studies) and the Mini-Mental State Examination
      (MMSE) score (MD 0.74; 95% CI 0.52 to 0.97, n = 3205, 6 studies), activities of
      daily living (SMD 0.20; 95% CI 0.13 to 0.27, n = 3230, 6 studies) and clinician
      rated global impression of changes, with a smaller proportion of patients treated
      with rivastigmine experiencing no change or a deterioration (OR 0.68; 95% CI 0.58
      to 0.80, n = 3338, 7 studies).Three studies reported behavioural change, and
      there were no differences compared to placebo (standardised mean difference (SMD)
      -0.04; 95% CI -0.14 to 0.06, n = 1529, 3 studies). Only one study measured the
      impact on caregivers using the Neuropsychiatric Inventory-Caregiver Distress (NPI
      D) scale and this found no difference between the groups (MD 0.10; 95% CI -0.91
      to 1.11, n = 529, 1 study). Overall, participants who received rivastigmine were
      about twice as likely to withdraw from the trials (odds ratio (OR) 2.01, 95% CI
      1.71 to 2.37, n = 3569, 7 studies) or to experience an adverse event during the
      trials (OR 2.16, 95% CI 1.82 to 2.57, n = 3587, 7 studies). AUTHORS' CONCLUSIONS:
      Rivastigmine (6 to 12 mg daily orally or 9.5 mg daily transdermally) appears to
      be beneficial for people with mild to moderate Alzheimer's disease. In
      comparisons with placebo, better outcomes were observed for rate of decline of
      cognitive function and activities of daily living, although the effects were
      small and of uncertain clinical importance. There was also a benefit from
      rivastigmine on the outcome of clinician's global assessment. There were no
      differences between the rivastigmine group and placebo group in behavioural
      change or impact on carers. At these doses the transdermal patch may have fewer
      side effects than the capsules but has comparable efficacy. The quality of
      evidence is only moderate for all of the outcomes reviewed because of a risk of
      bias due to dropouts. All the studies with usable data were industry funded or
      sponsored. This review has not examined economic data.

PMID- 25858346
TI  - Cultured blood T-cell responses predict anti-TNF therapy response in patients
      with ulcerative colitis.
AB  - BACKGROUND: Anti-tumour necrosis factor (TNF) therapy is used for treatment of
      ulcerative colitis (UC). As approximately 30% of patients with UC do not benefit
      from the treatment, it is of clinical interest to identify biomarkers of response
      before therapy is initiated. AIM: To identify prognostic biomarkers of anti-TNF
      therapy response in anti-TNF therapy-naive patients with UC. METHODS: Peripheral
      blood cells were obtained from 56 patients with UC before therapy started. Thirty
      four patients were included in an exploratory cohort and 22 patients in a
      validation cohort. Blood cells were stimulated in vitro with influenza vaccine
      with and without anti-TNF. T-cell surface receptor expression and cytokine
      release were determined (in total 17 variables). Treatment response was evaluated
      using the Mayo score 12-14 weeks after the first infusion. RESULTS: In the
      exploratory cohort, blood cells from the patients showed stronger anti-TNF
      dependent suppression of T-cell surface receptor expression and cytokine
      secretion among therapy responders than nonresponders. In particular, anti-TNF
      suppressed the expression of CD25 on T cells and secretion of interleukin 5, to a
      higher degree in responders than in nonresponders. These variables were used to a
      create model to predict therapy outcome, which was confirmed in the validation
      cohort. Correct classification of future therapy response was achieved in 91% of
      the cases in the validation cohort. CONCLUSION: The effects of anti-TNF on
      cultured blood T cells, obtained before therapy started, predict treatment
      outcome in patients with UC.

PMID- 25858347
TI  - Little do more: a highly effective Pt(1)/FeO(x) single-atom catalyst for the
      reduction of NO by H2.
AB  - A FeOx supported Pt single-atom catalyst (Pt-SAC) exhibited much higher NO
      conversion and selectivity to N2 than the supported Pt nanocatalyst (Pt-Nano).
      This better performance was attributed to not only the stronger NO adsorption and
      easier dissociation of the N-O bond but also the presence of more oxygen
      vacancies on the Pt-SAC. 

PMID- 25858348
TI  - A Comparative Study of Conservative versus Surgical Treatment Protocols for 77
      Patients with Idiopathic Granulomatous Mastitis.
AB  - The purpose of this study was to analyze the clinical features and demographic
      data of patients with idiopathic granulomatous mastitis (IGM) and to compare the
      results of conservative versus surgical treatment protocols. The demographic
      data, clinical findings, microbiological and pathologic features, scanning and
      treatment methods, recurrence, and recovery rates of 77 patients were analyzed
      retrospectively. The patients were divided into two groups based on the type of
      treatment received. Core biopsies were used to diagnose 37 patients: 26 using
      incisional biopsies and 14 using excisional biopsies. Of the patient population
      with IGM, 31 were treated with surgical excision, one with a simple mastectomy,
      and one with a subcutaneous mastectomy combined with a breast implant, whereas 44
      were treated with steroids. The recovery rates of the 44 patients who were
      treated conservatively were 6 (1-15) months while for the 33 patients who were
      treated surgically, it was 1 (1-5) month (p = 0.001). Nine patients from the
      conservative treatment group experienced a recurrence while there were no
      recurrences in the surgically treated group (p = 0.009). Among all patients, the
      recurrence rate was 11.7% (9/77) while the average follow-up period was 16.57 +/-
      18.57 months. As a comparative study between conservative treatment protocols and
      surgical ones for patients with idiopathic granulomatous mastitis (IGM), this
      study is the largest to date. A wide surgical excision is the preferred approach
      for treating patients with IGM because of the low recurrence rate. 

PMID- 25858349
TI  - Crystal preferred orientation of an amphibole experimentally deformed by simple
      shear.
AB  - Seismic anisotropy has been widely observed in crust and mantle materials and
      plays a key role in the understanding of structure and flow patterns. Although
      seismic anisotropy can be explained by the crystal preferred orientation (CPO) of
      highly anisotropic minerals in the crust, that is, amphibole, experimental
      studies on the CPO of amphibole are limited. Here we present the results of novel
      experiments on simple shear deformation of amphibolite at high pressure and
      temperatures (1 GPa, 480-700  degrees C). Depending on the temperature and
      stress, the deformed amphibole produced three types of CPOs and resulted in a
      strong seismic anisotropy. Our data provide a new understanding of the observed
      seismic anisotropy. The seismic data obtained from the amphibole CPOs revealed
      that anomalous seismic anisotropy observed in the deep crust, subducting slab and
      mantle wedge can be attributed to the CPO of amphibole.

PMID- 25858350
TI  - The Brief Memory and Executive Test (BMET) for detecting vascular cognitive
      impairment in small vessel disease: a validation study.
AB  - BACKGROUND: Cognitive impairment is common in patients with cerebral small vessel
      disease, but is not well detected using common cognitive screening tests which
      have been primarily devised for cortical dementias. We developed the Brief Memory
      and Executive Test (BMET); a rapid screening measure sensitive to the impaired
      executive function and processing speed characteristic of small vessel disease
      (SVD). To assess the BMET's validity for general use, we evaluated it when
      administered by non-psychologists in a multicentre study and collected control
      data to derive normative scores. METHODS: Two-hundred participants with SVD,
      defined as a clinical lacunar stroke and a corresponding lacunar infarct on MRI,
      and 303 healthy controls aged between 40-90 years old were recruited. The BMET,
      as well as the Montreal Cognitive Assessment (MoCA) and Mini Mental State
      Examination (MMSE), were performed. Overall, 55 SVD participants underwent repeat
      testing at 3 months to assess the BMET test-retest reliability. RESULTS:
      Administering the BMET took a mean (SD) of 12.9 (4.7) in cases and 9.5 (2.6)
      minutes in controls. Receiver Operator Curve analysis showed the BMET was a good
      predictor of cognitive impairment in SVD (AUC = 0.94) and performed significantly
      better than both the MoCA (AUC = 0.77) and the MMSE (AUC = 0.70). Using a cut-off
      score of 13, the BMET had a sensitivity of 93% and specificity of 76% for
      detecting cognitive impairment in SVD. CONCLUSIONS: The BMET is a brief and
      sensitive tool for the detection of cognitive impairment in patients with SVD.

PMID- 25858351
TI  - Systemic vasculitis and pregnancy: a multicenter study on maternal and neonatal
      outcome of 65 prospectively followed pregnancies.
AB  - OBJECTIVE: Systemic vasculitis (SV) are uncommon diseases that rarely affect
      women during their reproductive age; little data, mainly retrospective, is
      available on this topic. The aim of our study was to evaluate maternal/neonatal
      outcome and disease course before, during and after pregnancy. METHODS: Sixty
      five pregnancies in 50 women with SV were followed by a multispecialistic team in
      8 institutions between 1995 and 2014. Clinical data on pregnancy, 1year before
      and 1year after delivery was retrospectively collected. The rate of pregnancy
      complications was compared to that of a General Obstetric Population (GOP) of
      3939 women. RESULTS: In 2 patients the diagnosis of SV was done during pregnancy;
      59 out of the remaining 63 started when maternal disease was quiescent. We
      recorded 56 deliveries with 59 live births, 8 miscarriages and 1 fetal death. In
      SV, preterm, particularly early preterm (<34weeks) deliveries and cesarean
      sections appeared significantly more frequent than in GOP (11.3% vs 5.0%, p=0.049
      and 48.2% vs 31.0%, p=0.009). Vasculitis-related complications occurred in 23
      pregnancies (35.4%), with 5 severe events (7.7%) including 3 cases of transient
      ischemic attack (TIA). Data about the post-partum period were available for 56
      pregnancies: 12 flares (21.4%) occurred, with 1 severe event (1.8%). CONCLUSION:
      SV patients can have successful pregnancies (especially during a disease
      remission phase) despite an increased rate of preterm delivery. Severe flares
      were limited, but the occurrence of 3 TIA suggests that particular attention
      should be given to possible thrombotic complications in SV patients during
      pregnancy and puerperium.

PMID- 25858352
TI  - A New Hierarchy of Phylogenetic Models Consistent with Heterogeneous Substitution
      Rates.
AB  - When the process underlying DNA substitutions varies across evolutionary history,
      some standard Markov models underlying phylogenetic methods are mathematically
      inconsistent. The most prominent example is the general time-reversible model
      (GTR) together with some, but not all, of its submodels. To rectify this
      deficiency, nonhomogeneous Lie Markov models have been identified as the class of
      models that are consistent in the face of a changing process of DNA substitutions
      regardless of taxon sampling. Some well-known models in popular use are within
      this class, but are either overly simplistic (e.g., the Kimura two-parameter
      model) or overly complex (the general Markov model). On a diverse set of
      biological data sets, we test a hierarchy of Lie Markov models spanning the full
      range of parameter richness. Compared against the benchmark of the ever-popular
      GTR model, we find that as a whole the Lie Markov models perform well, with the
      best performing models having 8-10 parameters and the ability to recognize the
      distinction between purines and pyrimidines. 

PMID- 25858353
TI  - Adsorbate enhancement of electron emission during the quenching of metastable CO
      at metal surfaces.
AB  - When electronically excited CO(a(3)Pi) collides with a Au(111) surface, electron
      emission can be observed with a quantum efficiency of 0.13. We have studied the
      influence of Ar, Kr and Xe adsorption on the electron emission efficiency
      resulting from CO(a(3)Pi) quenching. Surprisingly, a single monolayer (ML) of
      rare gas dramatically enhances electron emission. For Ar and Kr bilayers,
      emission efficiency is further enhanced and approaches unity. The quenching
      mechanism involves electron transfer from the metal to the CO(a(3)Pi) molecule
      followed by electron emission from the molecule. The enhanced emission efficiency
      is due to the long range nature of the initial electron transfer process and the
      rare gas adlayer's ability to reflect the electron emitted by the transient CO
      anion. This work shows that CO(a(3)Pi) quenching is a useful model system for
      investigating the fate of electronically excited molecules at surfaces. 

PMID- 25858354
TI  - Is infant exposure to antiretroviral drugs during breastfeeding quantitatively
      important? A systematic review and meta-analysis of pharmacokinetic studies.
AB  - OBJECTIVES: The objectives of this study were to summarize antiretroviral drug
      concentrations in breast milk (BM) and exposure of breast-fed infants. METHODS:
      This was a systematic review of pharmacokinetic studies of HIV-positive women
      taking antiretrovirals that measured drugs in BM. The quality of pharmacokinetic
      and laboratory methods was assessed using pre-defined criteria. Pooled ratios and
      95% CIs were calculated using the generalized inverse variance method and
      heterogeneity was estimated by the I(2) statistic. PubMed Central, SCOPUS and
      LactMed databases were searched. No date or language restrictions were applied.
      Searches were conducted up to 10 November 2014. Clinical relevance was estimated
      by comparing ingested dose with the recommended therapeutic dose for each drug.
      RESULTS: Twenty-four studies were included. There was substantial variability in
      the clinical and laboratory methods used and in reported results. Relative to
      maternal plasma (MP), NRTIs accumulate in BM, with BM : MP ratios (95% CI
      estimates) from 0.89 to 1.21 (14 studies, 1159 paired BM and MP samples). NNRTI
      estimates were from 0.71 to 0.94 (17 studies, 965 paired samples) and PI
      estimates were from 0.17 to 0.21 (8 studies, 477 paired samples). Relative to the
      recommended paediatric doses, a breast-fed infant may ingest 8.4% (95% CI 1.9
      15.0), 12.5% (95% CI 2.6-22.3) and 1.1% (95% CI 0-3.6) of lamivudine, nevirapine
      and efavirenz, respectively, via BM. CONCLUSIONS: Transfer to untreated infants
      appears quantitatively important for some NRTIs and NNRTIs. The pharmacokinetic
      methods varied widely and we propose standards for the design, analysis and
      reporting of future pharmacokinetic studies of drug transfer during
      breastfeeding.

PMID- 25858355
TI  - A novel small-molecule inhibitor of hepatitis C virus replication acts by
      suppressing signal transducer and activator of transcription 3.
AB  - OBJECTIVES: Hepatitis C virus (HCV) infects hepatocytes and causes liver damage.
      The aim of this study was to identify new classes of host-targeting anti-HCV
      compounds that may provide novel approaches for antiviral treatment regimens.
      METHODS: Cell culture-derived HCV (HCVcc), replicons and pseudoparticles were
      used in combination with high-throughput screening, reporter gene assays and
      cytotoxicity and signalling pathway analyses. RESULTS: A small-molecule inhibitor
      of HCV, N-(cyclopropyl(phenyl)methyl)thieno[2,3-d]pyrimidin-4-amine, designated
      IB-32, was identified by screening a compound library with a Jc1-luc HCVcc assay.
      By using various virus models, HCV replication was identified as the predominant
      step of IB-32's action. IB-32 inhibited HCVcc (genotype 2a) and HCV replicons
      (genotype 1b) at low nanomolar ranges (with IC50s of 40 +/- 8 and 100 +/- 15 nM,
      respectively). IB-32 was found to be non-toxic when tested against a panel of
      human cell lines in vitro at the effective antiviral dose. Mechanistically, IB-32
      strongly inhibited STAT3 (Tyr705) phosphorylation, a necessary cellular factor
      for HCV replication and a pivotal therapeutic target for multiple cancers.
      Furthermore, the inhibition of HCV replication by IB-32 was augmented in cells
      with STAT3 knockdown. In contrast, the inhibitory effect of IB-32 was attenuated
      in cells overexpressing a constitutively active form of STAT3. CONCLUSION: The
      results presented here identify a promising STAT3-targeting anti-HCV therapeutic
      candidate. This novel small molecule could be further optimized and developed for
      use as both an antiviral and an anti-cancer drug.

PMID- 25858357
TI  - Validation of the Japanese version of the Chronic Liver Disease Questionnaire for
      the assessment of health-related quality of life in patients with chronic viral
      hepatitis.
AB  - AIM: Patients with chronic liver diseases (CLD) suffer from a variety of
      subjective symptoms, and the assessment of health-related quality of life (HRQOL)
      is crucial. The Chronic Liver Disease Questionnaire (CLDQ) is the first liver
      disease-specific instrument for this purpose. In this study we aimed to develop
      the Japanese version of CLDQ and to assess its validity and reliability in
      Japanese patients with chronic viral hepatitis. METHODS: The participants
      included 135 Japanese patients chronically infected with hepatitis B or C virus.
      The Japanese version of the CLDQ was developed according to the standard "back
      translation" method. In addition to the Japanese version of the CLDQ, we asked
      the patients to fill out two other self-report questionnaires: the Japanese
      versions of the 36-Item Short Form Survey (SF-36) and Hospital Anxiety and
      Depression Scale (HADS). Then, the internal consistency, convergent and
      discriminant validity of the Japanese version of CLDQ were statistically
      examined. RESULTS: Cronbach's alpha of the Japanese version of the CLDQ was
      acceptable. The mean score was lower in emotional domains of the CLDQ, compared
      with those in somatic domains. Pearson correlations between Japanese CLDQ and SF
      36 and HADS were significant. The mean of the CLDQ scores decreased in all
      domains in patients with liver cirrhosis compared with those in patients with
      chronic hepatitis. CONCLUSION: The Japanese version of the CLDQ is a reliable and
      valid instrument for assessment of the HRQOL of Japanese patients with chronic
      viral hepatitis. The results also suggest that the HRQOL of Japanese patients is
      mainly impaired by emotional factors rather than somatic symptoms, and
      significantly worsened by progression of the disease.

PMID- 25858356
TI  - Extremely high prevalence of antiseptic resistant Quaternary Ammonium Compound E
      gene among clinical isolates of multiple drug resistant Acinetobacter baumannii
      in Malaysia.
AB  - BACKGROUND: Antiseptics are commonly used for the management of MDR (multiple
      drug resistance) pathogens in hospitals. They play crucial roles in the infection
      control practices. Antiseptics are often used for skin antisepsis, gauze
      dressing, preparation of anatomical sites for surgical procedure, hand
      sterilization before in contact with an infected person, before an invasive
      procedure and as surgical scrub. METHODS: We screened 122 multiple drug resistant
      Acinetobacter baumannii (MDRAB) isolated from admitted patients in one of the
      tertiary care hospital in Malaysia for the presence of antiseptic resistant genes
      qacA and qacE (Quaternary Ammonium Compound) and susceptibility towards
      chlorhexidine (CLX), benzalkonium (BZK) and benzethonium (BZT). RESULTS: Eighty
      nine (73%) isolates harboured qacE gene, while none were positive for qacA. The
      MIC ranged from 0.2 to 0.6 for CLX, 0.02 to 0.2 for BZK and 0.04 to 0.2 MUg/mL
      for BZT. The highest number of qacE positive isolates were obtained from surgery
      (n = 24; 27%; p < 0.05), followed by medical ward (n = 23; 25.8%) and ICU (n =
      21; 23.6%). Majority of the isolates from wound swabs (n = 33; 37%), T/aspirate
      (n = 16; 18%) and tissue (n = 10; 11.2%) harboured the qacE genes. CONCLUSION:
      The present investigation showed high prevalence of qacE gene among the studied
      isolates. Antiseptics are important components of infection control, continuous
      monitoring of antiseptics use in the hospital is cautioned.

PMID- 25858358
TI  - Mechanisms of ibrutinib resistance in chronic lymphocytic leukaemia and non
      Hodgkin lymphoma.
AB  - Bruton tyrosine kinase (BTK), a mediator of B-cell receptor (BCR) signalling, has
      been implicated in the pathogenesis of chronic lymphocytic leukaemia (CLL) and
      other B-cell malignancies. Ibrutinib is an orally bioavailable and highly
      specific BTK inhibitor that was recently approved for treatment of patients with
      recurrent CLL and mantle cell lymphoma (MCL). In addition, ibrutinib has shown
      efficacy in subsets of patients with diffuse large B cell lymphoma (DLBCL) and
      Waldenstrom macroglobulinaemia (WM). However, despite ibrutinib's activity in
      multiple B-cell malignancies, cases of primary and secondary resistance have
      emerged. The overall reported frequency of resistance is low, but follow-up in
      many trials was short, and we predict that the incidence of observed resistance
      will increase as clinical use outside clinical trials expands over time.
      Mutations within BTK have been described and clearly interfere with drug binding;
      however, there are also emerging alternative mechanisms that bypass BTK entirely
      and offer new opportunities for other targeted agents. Improved understanding of
      mechanisms of primary and secondary resistance is essential to developing
      appropriate therapeutic strategies to both prevent and address resistance. This
      review provides a comprehensive analysis of ibrutinib resistance in CLL, MCL,
      DLBCL and WM and considers potential strategies for further study. 

PMID- 25858360
TI  - Simple synthesis of conformationally fixed glycosamine analogues by beckmann
      rearrangement at the carbohydrate ring.
AB  - Conformationally fixed carbohydrate analogues are promising small-molecule
      inhibitors for hydrolases like O-GlcNAcase (OGA); however, their synthesis
      usually requires many steps. Herein we describe cycloadditions of dichloroketene
      to various glycals and subsequent Beckmann rearrangements, which offer an easy
      and stereoselective entry to glycosamine derivatives in good yields. The
      reactions are applicable for hexoses, pentoses, and disaccharides, and
      transformations to the corresponding imidates proceed smoothly. First biological
      tests reveal that such imidates indeed inhibit human OGA. 

PMID- 25858361
TI  - [The effect of fluoride on the expression of GRP-78 and caspase-12 in rat
      ameloblast].
AB  - PURPOSE: To study the effect of GRP-78 and caspase-12 on fluoride-induced
      endoplasmic reticulum stress and apoptosis in rat ameloblast, and explore whether
      fluoride-induced endoplasmic reticulum stress results in the occurrence of
      apoptosis. METHODS: The cell activity of ameloblast cultured in various
      concentrations of fluoride was measured by CCK8 and flow cytometry; Real-time RT
      PCR and Western blot were used to analyze the endoplasmic reticulum chaperone GRP
      78 and caspase-12 genes and the expression of related proteins. The data was
      analyzed with SPSS13.0 software package. RESULTS: With the increasing
      concentration of fluoride, the cell activity of rat ameloblasts decreased
      gradually, and flow cytometry also showed that the number of apoptosis gradually
      increased; Real-time RT-PCR and Western blot showed the expression of GRP-78 and
      caspase-12 increased while the fluoride concentration increased. CONCLUSIONS:
      Excessive fluoride induces endoplasmic reticulum stress of rat ameloblast, and
      leads to cell apoptosis.

PMID- 25858359
TI  - Structural asymmetry of the insula is linked to the lateralization of gesture and
      language.
AB  - The control of gesture is one of the most left-lateralized functions, and the
      insular cortex is one of the most left-biased structures in the human brain.
      Therefore, we investigated whether structural asymmetries of the insula are
      linked to the organization of functional activity during gesture planning. We
      reconstructed and parcellated the insular cortex of 27 participants. First, we
      tested 15 strongly left-handed individuals because of a higher incidence of
      atypical organization of functions such as gesture and language in such a
      population. The inter-hemispheric structural asymmetries were compared with the
      lateralization of activity for gesture in the supramarginal gyrus (the hotspot of
      signal increase regardless of the gesturing hand) and Broca's area (the hotspot
      of signal increase for language production). The more pronounced leftward
      structural asymmetries were accompanied by greater left-hemisphere dominance for
      both of the studied functions. Conversely, an atypical, bilateral or rightward
      functional shift of gesture and language was accompanied by an attenuated
      leftward asymmetry of the insula. These significant relationships were driven
      primarily by differences in surface area. Subsequently, by adding 12 right-handed
      individuals to these analyses we demonstrated that the observed significant
      associations are generalizable to the population. These results provide the first
      demonstration of the relationships between structural inter-hemispheric
      differences of the insula and the cerebral specialization for gesture. They also
      corroborate the link between insular asymmetries and language lateralization. As
      such, these outcomes are relevant to the common cerebral specialization for
      gesture and language. 

PMID- 25858362
TI  - [Expression of TRPV1 and CGRP in rat trigeminal ganglion during orthodontic tooth
      movement].
AB  - PURPOSE: Sprague-Dawley rat models of tooth movement were established to
      investigate the expression of transient receptor potential vanilloid 1 (TRPV1)
      and calcitonin gene related peptide (CGRP) in rat trigeminal ganglion during
      orthodontic tooth movement, and to explore the roles of TRPV1 and CGRP in
      orthodontic pain. METHODS: Sixty-six Sprague-Dawley rats were randomly divided
      into control group (n=6), sham operation group (n=6), and experimental group
      (n=54). Tooth movement models were established, orthodontic force (50 g) was
      applied on the maxillary first molar in the rats of experimental group, and then
      the trigeminal ganglia were collected at 4, 8 h, 1 d (3 subgroups were set up
      according to the force: 1 d-30 g, 1 d-50 g, 1 d-80 g), 3, 5, 7, 14 d after tooth
      movement. The changes of TRPV1 and CGRP expression were detected by
      immunofluorescence staining. SPSS16.0 software package was used for statistical
      analysis. RESULTS: According to immunofluorescence staining, the TRPV1-IR and
      CGRP-IR neurons were mostly small to medium sized. The percentages of TRPV1-IR
      and CGRP-IR neurons in trigeminal ganglion increased after applying force, and
      reached the peak at 1-3 d and then fell to the initial level gradually. In
      addition, the application of greater force during experimental tooth movement
      induced higher percentages of TRPV1-IR and CGRP-IR neurons in trigeminal
      ganglion. CONCLUSIONS: Experimental tooth movement leads to the regular changes
      of TRPV1-IR and CGRP-IR neurons in trigeminal ganglion, indicating that TRPV1 and
      CGRP may play important roles in orthodontic pain.

PMID- 25858363
TI  - [The effect of denture base resins coated with antibacterial coating on water
      sorption, solubility and monomer elution].
AB  - PURPOSE: To determine the influence of denture base resins coated with
      antibacterial coating on water sorption, solubility and monomer elution. METHODS:
      The values of water sorption and solubility were measured according to YY 0270
      2003 and gas chromatography was used to examine the leachability of 4
      commercially available heat-cured acrylic resins between experimental group and
      control group. Degree of crosslinking of the experimental heat-cured acrylic
      denture bases we remeasured by soxhlet extraction method. The data was analyzed
      by 17.0 software package. RESULTS: The values of water sorption, solubility and
      monomer elution of experimental group were lower compared to the control group.
      Degree of crosslinking of Heraeus reins was the highest among the experimental
      heat-cured acrylic denture bases. CONCLUSIONS: There is a same trend among water
      sorption, degree of crosslinking and the monomer elution. When the degree of
      crosslinking increases, the values of water sorption and monomer elution
      decrease. Antibacterial coating can improve the comprehensive properties of the
      denture base resins.

PMID- 25858364
TI  - [In vitro remineralization effect of grape seed extract on artificial dentin
      caries].
AB  - PURPOSE: To evaluate the effect of grape seed extract (GSE) on remineralization
      of artificial dentin caries. METHODS: Sixty human dentine fragments were stored
      in a demineralization solution for 24 h at 37 degrees centigrade to induce
      artificial dentin caries lesions. The fragments were then randomly divided into 4
      groups: 10% GSE, 1 mg/L NaF, 10% GSE+1 mg/L NaF and distilled water (DDW, as
      control). The demineralized samples were pH-cycled for 8 days and surface dentine
      microhardness was assessed before and after pH-cycling regimen. The percentage
      surface microhardness recovery (SMHR) was calculated. The samples were
      subsequently analyzed with scanning electron microscopy (SEM) and energy
      dispersive X-ray spectrometry (EDXS). The date was analyzed using ANOVA and
      Fisher's tests by SPSS17.0 software package. RESULTS: The percentage surface
      microhardness recovery (SMHR) was obtained for GSE, NaF, GSE+NaF and DDW
      group(40.87 +/- 9.92,44.60 +/- 12.48, 48.54 +/- 9.27 and 15.98 +/- 8.33,
      respectively). The treatment groups significantly increased the microhardness of
      the lesions (P<0.05) compared to DDW group, with no statistically significant
      difference among the treatment groups(P>0.05). Scanning electron microscopy of
      the treatment groups revealed greater mineral deposition on dentinal tubules, and
      DDW group formed honeycomb structure. Furthermore, from EDXS data, the treatment
      groups had higher percentage of Ca and P than the control. CONCLUSIONS: GSE
      positively affects the remineralization processes of artificial dentinal caries
      lesions, which may be a promising natural agent for remineralization therapy
      instead of fluoride.

PMID- 25858365
TI  - [Facial motoneurons death and caspase regulatory gene expression following facial
      nerve injury].
AB  - PURPOSE: To investigate the morphology of facial motoneurons and its death course
      as well as caspase 3, caspase 8, cyto-c death proteins' expression and their
      correlation following facial nerve distal transection or crush in rats. METHODS:
      The right facial nerve underwent distal transaction and crush as experimental
      group, while the left facial nerve acted as normal control. We observed the
      morphology and the death course of motoneurons by light microscope and
      transmission electron microscope. Expressions of caspase 3, 8, and cyto-c protein
      were studied by immunohistochemistry (S-P) and image analysis. SPSS 10.0 software
      package was used for statistical analysis. RESULTS: (1) Both axon distal
      transection and axon crush resulted in death of facial motoneurons. The
      motoneurons' loss reached peak 28 days after injuries and were mainly through
      apoptotic pathway. The number of motoneurons' loss in the distal transection
      group were more than that in the crush group. (2) Caspase 3, caspase 8 and cyto-c
      protein expressions were observed in wide spread areas of normal rat facial
      nucleus. In addition to neurons, glial cells were also stained. Cells of the
      distal transection group stained more strongly than that of crush group.
      Expressions of the proteins began to increase 3 days after the injuries. Caspase
      3 and caspase 8 protein expression reached peak 14 days whereas cyto-c protein
      expression reached peak 7 days after the injuries. Expression of caspase 8 and
      cytoc protein were correlated with expression of caspase 3 protein. CONCLUSIONS:
      (1)Different facial nerve injuries result in death of facial motoneurons. The
      loss of motoneurons is related with the injuries' patterns. Clinical nerve
      reparation should be performed as early as possible within 4 weeks after the
      transection. (2)The expression of caspase 3, 8 and cyto-c protein were related
      with facial nerve injuries' patterns. Caspase 8 and cyto-c protein expressions
      were correlated with caspase 3 protein expression, indicating that caspase 8 and
      cyto-c may take part in activating caspase 3. Caspase cascade reaction may have
      an important role in the apoptosis of facial motoneurons.

PMID- 25858366
TI  - [Mechanism of chloroquine in promoting sensitivity of chemotherapeutics in oral
      squamous cell carcinoma CAL-27 cell line to cisplatin].
AB  - PURPOSE: To study the role and mechanism of autophagy in chemotherapy of oral
      squamous cell carcinoma, and provide theoretical evidence to improve
      chemotherapeutic efficacy of oral squamous cell carcinoma patients. METHODS: The
      cell survival rate changes induced by cisplatin (DDP) and chloroquine (CQ) in CAL
      27 cells were assayed by methyl thiazolyl tetrazolium method(MTT). The LC3-II
      expression level was detected by laser scanning confocal microscope; The
      apoptotic rate was determined by flow cytometry. SPSS17.0 software package was
      used for statistical analysis. RESULTS: MTT results showed that compared with the
      control group, the cell survival rate reduced with the increasing time of DDP and
      CQ treatment; The optimal concentration of CAL-27 cells was 5 mg/L after
      treatment with CQ. IC50 of the CAL-27 cells was 5 mg/L after treatment with DDP;
      MTT results showed that the cell survival rate of CQ+DDP group was significantly
      lower than control group, CQ group and DDP group (P<0.05). With the action of CQ
      and DDP to CAL-27 cells for 48 hours, immunofluorescence results showed that the
      average fluorescence intensity of DDP group was significantly higher than the
      other 3 groups (P<0.05), while it was significantly lower in CQ group than the
      other 3 groups (P<0.05). With the action of CQ and DDP to CAL-27 cells for 48
      hours, flow cytometry results showed that the cell apoptosis rate of DDP group
      and CQ+DDP group were significantly higher than control group and CQ group. The
      cell apoptosis rate of CQ+DDP group was significantly higher than DDP group
      (P<0.05). With the action of CQ and DDP to CAL-27 cells for 48 hours, cells in G1
      phase of DDP group and CQ+DDP group increased, indicating G1 phase blockage. The
      cell count in G1 phase of CQ+DDP group was significantly higher than DDP group
      (P<0.05). CONCLUSIONS: Inhibition of autophagy can enhance the chemotherapeutic
      sensitivity of DDP in CAL-27 cells. Autophagy in CAL-27 cells is an important
      mechanism for chemotherapy resistance of oral squamous cell carcinoma. Autophagy
      inhibitor may have significant potential to be a novel chemotherapeutic
      sensitizer for oral squamous cell carcinoma.

PMID- 25858367
TI  - [Establishment of animal model with peri-implantitis after immediate implantation
      in rabbits].
AB  - PURPOSE: To establish animal model with peri-implantitis after immediate
      implantation and study bone defect characteristics by Micro-CT. METHODS: Implants
      were immediately planted in the first mandibular anterior tooth of 12 rabbits.
      Silk ligatures were placed around one side of the implants to induce peri
      implantitis. Micro-CT was used to evaluate bone defect at different periods after
      implantation. RESULTS: Silk ligatures around the implants were effective to
      induce peri-implantitis. With the development of peri-implantitis, implants can
      not be well integrated with bone. Bone defect was gradually produced and then
      aggravated, and finally formed typical "V-type" bone defect. CONCLUSIONS: The
      establishment of animal model with peri-implantitis is simple and effective,
      which provides important references for relative studies in the field of peri
      implantitis.

PMID- 25858368
TI  - [Expression of MMP-2 in the periodontal tissues with the mini-screw for molar
      intrusion with cyclic intrusive force in dogs].
AB  - PURPOSE: To observe the expression of MMP-2 in the periodontal tissues of molars
      in Beagle dogs after different times of intrusion by mini-screw with cyclic
      intrusive force. METHODS: Three mature Beagle dogs were used for the experiment.
      On the buccal and palatal sites of the left maxillary second and third premolars,
      a minis-crew was placed at the inter-radicular septa separately, intruding the
      tooth with 150 g initial force, which would be reinforced every 4 weeks. The
      teeth of left side as the experimental group were divided into 3 subgroups, as
      being intruded 12, 24 and 36 weeks, and the right side as blank control. Then the
      dogs were sacrificed, and the second and the third premolars with the surrounding
      periodontal tissue were cut down, fixed, decalcified, wrapped and cut into
      slices. Immunohistochemical staining with MMP-2 was performed. The average
      optical density (OD) of MMP-2 was calculated with IPP software, which represented
      the expression of MMP-2. SPSS 17.0 software package was used for statistical
      analysis. RESULTS: Immunohistochemical staining revealed that the expression of
      MMP-2 in control group was low. After tooth intrusion, MMP-2 expression
      significantly increased in the periodontal tissues of molars, and reached the
      maximum in the group of 24 weeks. Then MMP-2 expression decreased in the 36-week
      group but still significantly higher than the control group. There was no
      significant difference among the 3 subgroups for different intrusion
      times(P>0.05). CONCLUSIONS: MMP-2 participates in remodeling of the periodontal
      tissue during tooth intrusion. The expression of MMP-2 is not significantly
      increased with the extension of the intrusion time with cyclic intrusive force,
      which suggests that with the use of mini-screw to intrude the molars with cyclic
      intrusive force, the periodontal tissues of the intruded tooth maintain dynamic
      balance of bone remodeling.

PMID- 25858369
TI  - [Study of relationship between (Ca+Zn)/P of pure titanium surface coating and
      biological activity of osteoblasts].
AB  - PURPOSE: To study osteoblast (MC3T3-E1 cells) adhesion, proliferation and
      differentiation activity on the surface of pure titanium with different (Ca+Zn)/P
      ratios, and determine Ca, P, Zn contents offering best biological activity on
      pure titanium surface. METHODS: In the micro-arc oxidation electrolyte, Ca, P
      with a certain concentration, and 5 different concentrations of Zn (0, 0.01,
      0.03,0.04, and 0.06 mol/L) were added, which made the mole ratio of Ca and P
      element close to the ratio of hydroxyapatite. (Ca+Zn)/P ratio of bioactive
      coating on 5 different pure titanium material surfaces were prepared, which named
      S0 and S1, S2, S3 and S4 group, respectively. The surface elements, existence
      form, (Ca+Zn)/P ratio and surface morphology were analyzed by XPS and SEM; MC3T3
      E1 cells adhesion, proliferation and differentiation cultured on the material
      surface were analyzed by SEM, MTT method and ALP activity assay. RESULTS: The
      data was analyzed with SPSS13.0 software package. With the increase of Zn content
      in the electrolyte, (Ca+Zn)/P ratios were 2.94, 2.64 2.71, 2.87 and 2.72 in S0-S4
      group, respectively. (Ca+Zn)/P ratio was maximal in S3 group and decreased in S4
      group. MC3T3-E1 cell adhesion, proliferation and differentiation capacity on
      material surface of 5 groups changed in the following order: 3>S4>S2>S1>S0, with
      significant differences among 5 groups (P<0.05). CONCLUSIONS: Coating with
      different concentrations of Ca, P, Zn on pure titanium surface by micro-arc
      oxidation technique, the adhesion, proliferation and differentiation ability of
      osteoblast increase as (Ca+Zn)/P ratio increase, and cell biological activity is
      the best when the (Ca+Zn)/P ratio reached 2.87.

PMID- 25858370
TI  - [Effect of 3 polishing methods on microleakage of 2 kinds of resin composite
      restorations].
AB  - PURPOSE: To evaluate the effect of different polishing methods on microleakage of
      different resin composite restorations (Filtek Z350 and Filtek Z250). METHODS:
      Standardized preparations (the box-type cavities, 3 mm in length and width,2 mm
      in depth) were prepared at the cemento-enamel junction on buccal surface of 80
      premolars. They were randomly divided into 2 groups, and restored with
      composites( Filtek Z350 or Filtek Z250). Based on polishing methods, the
      specimens of each group were randomly classified into 4 subgroups: no polishing,
      polishing with Soflex discs, polishing with Super-snap discs and polishing with
      diamond burs. After thermal circulation (2000 times, 5-55 degrees centigrade) and
      soaked for 24 hours in 2% methyl blue solution, the specimens were cut through
      the midline of the restoration, the microleakage at the occlusal margin and the
      gingival margin were observed under a stereomicroscope and the leakage depth was
      measured with Spot version 4.6 software package. The microleakage width and
      microleakage depth of different groups were analyzed with SPSS 17.0 software
      package for Mann -Whitney U test and Kruskal-Wallis test. RESULTS: The
      microleakage depth of Filtek Z350 groups was (0.655 +/- 0.486) mm, (0.626 +/-
      0.497) mm,(0.634 +/- 0.345) mm and (0.875 +/- 0.283) mm, respectively. The
      microleakage depth of Filtek Z250 groups was (0.785 +/- 0.553) mm, (0.763 +/-
      0.491) mm,(0.789 +/- 0.308) mm and (0.942 +/- 0.318) mm. The microleakage depth
      of specimens polishing with diamond burs was significantly deeper than that of
      other groups. There was no significant difference among specimens with no
      polishing, polishing with Soflex discs and polishing with Super-snap discs.
      CONCLUSIONS: The polishing system of Soflex discs and Super-snap discs have no
      significant influence on microleakage of resin composite restorations.

PMID- 25858371
TI  - [p38 signal pathway regulates osteogenic differentiation of maxillary primordium
      mesenchymal cells].
AB  - PURPOSE: To explore whether p38 signal pathway regulates osteogenic
      differentiation of maxillary primordium mesenchymal cells. METHODS: The first
      passage of maxillary primordium mesenchymal cells (MPMCs) from E12.5 embryos were
      cultured in the osteogenic medium, and 10 nM SB203580 (an inhibitor of
      phosphorylation of p38) was added in the medium in the experimental group for 1
      week. Then immunofluorescence staining was applied to detect the phosphorylation
      of p38 in MPMCs. Brdu label and immunofluorescence staining were used to detect
      the proliferation of MPMCs. ALP staining and qPCR were used to detect the mRNA
      expression of ALP, Runx2, OCN and OPN in MPMCs. ALP staining and PCR were used to
      evaluate the osteogenic capability of MPMCs. SPSS 18.0 software package was used
      to analyze the data. RESULTS: Osteogenic induction could promote phosphorylation
      of p38, inhibit phosphorylation of p38 and proliferation of MPMCs, down-regulate
      the expression of ALP, Runx2, OCN and OPN, thus weaken the ALP staining in MPMCs.
      CONCLUSIONS: p38 signal pathway regulates osteogenic differentiation of MPMCs in
      vitro.

PMID- 25858372
TI  - [The effect of platelet-rich fibrin on biologic characteristics of osteoblasts].
AB  - PURPOSE: To investigate the effect of platelet-rich fibrin on biologic
      characteristics of osteoblasts. METHODS: Osteoblasts were cultured with or
      without a PRF membrane. The cell proliferation was detected by MTT. The alkaline
      phosphatase (ALP) stain and the positive expression of collagen type I,
      osteoprotegerin and RANKL were measured. The data was statistically analyzed with
      SPSS17.0 software package. RESULTS: PRF promoted cell proliferation and increased
      expression of ALP, collagen typeI and OPG significantly, but there was no
      significant impact on expression of RANKL. CONCLUSIONS: PRF promotes osteoblasts
      proliferation, differentiation and OPG expression. PRF is involved in bone
      remodeling via regulating expression of OPG and RANKL.

PMID- 25858373
TI  - [Expression and clinical significance of plasma microRNA-125b level in patients
      with oral squamous cell carcinoma].
AB  - PURPOSE: To explore the expression and clinical significance of plasma microRNA
      125b (miR-125b) in patients with oral squamous cell carcinoma (OSCC). METHODS: By
      Stem-loop RT real-time PCR based on the SYBR Green, we investigated the
      expression of plasma miR-125b in 85 OSCC patients and 46 healthy controls, then
      evaluated its diagnostic performance as OSCC biomarker. Data analysis was
      performed with SPSS 17.0 software package for one-way ANOVA and receiver
      operating characteristic (ROC) curve. RESULTS: Stem-loop RT-PCR could
      specifically amplify miR-125b in plasma. The expression of plasma miR-125b was
      significantly increased in patients with OSCC compared with healthy controls
      (P<0.05). ROC results showed that miR-125b could differentiate OSCC from healthy
      controls(AUC=0.966). As fold change 3.46 was chosen for optimal cutoff value, the
      diagnostic sensitivity and specificity was 89.4% and 93.5%, respectively.
      CONCLUSIONS: Due to the satisfactory diagnostic performance, plasma miR-125b can
      be used as a promising biomarker in OSCC.

PMID- 25858374
TI  - [Treatment of adult bimaxillary arch protrusion with micro-implant anchorage].
AB  - PURPOSE: In this study, micro-implants were used in 15 adult patients with mild
      and moderate bimaxillary arch protrusion or crowding. Cephalometric analysis was
      used to analyze hard and soft-tissues change before and after treatment, with the
      aim to investigate the effects of treatment on adult bimaxillary arch protrusion
      with micro-implant anchorage. METHODS: Fifteen adult patients with mild and
      moderate bimaxillary arch protrusion were selected in this study. Micro-implants
      were inserted into the zygomaticoalveolar ridge of maxilla and the external
      oblique line of mandible. A NiTi coil spring was attached to the micro-implant to
      drag the whole upper and lower dentition for distal movement. Cephalometrics were
      taken before and after treatment, and the changes of soft and hard-tissue profile
      were studied. SPSS13.0 software package was used to analyze the data. RESULTS:
      (1)Sixty micro-implants remained stable.(2)SNA, SNB had no significant changes
      (P>0.05), and the relationship between the maxilla and the mandible did not
      change significantly. U1/NA, U1-NA, L1/NB, L1-NB and U1/L1 changes in hard tissue
      had significant difference in cephalometric measurement (P<0.05). The upper and
      lower anterior teeth were more retrusive, and the tipping of incisor decreased
      significantly.(3)Cephalometric analysis showed that lateral appearance improved
      and soft tissue cephalometric-related measurements such as Cm-Sn-UL,LL-B'-Pos
      increased significantly (P<0.01). (4)Molars and incisors acquired distal
      movement. CONCLUSIONS: Micro-implant can provide not only excellent skeletal
      anchorage but also a novel way to distalize the whole dentition efficiently.

PMID- 25858375
TI  - [BMP2/BMP4 genetic evaluation in 40 patients with tooth agenesis].
AB  - PURPOSE: To evaluate the potential mutation in BMP2/BMP4 genes in Chinese
      patients with non-syndromic hypodontia. METHODS: Genomic DNA was isolated from
      blood samples of 40 non-syndromic hypodontia Chinese patients. One hundred
      unrelated individuals, who were not affected with tooth agenesis (excluding third
      molars), were used as controls. PCR was performed to amplify each exon of
      BMP2/BMP4 genes. Gel-purified PCR fragments were sequenced to detect mutations.
      SPSS13.0 software package was used to analyze the data. RESULTS: We identified 4
      single nucleotide polymorphisms (SNPs) BMP2, c.109T>G p.Ser37Ala; c.261A> G
      p.Ser87Ser; c.570A>T p.Arg190Ser; BMP4 c.455T> C p.Val152Ala; and a novel
      mutation BMP2 c.166C> G p.Arg56Gly within the family. CONCLUSIONS: Our finding
      suggests that all the identified SNPs and the new mutation of BMP2 may be
      responsible for tooth agenesis in the participants, but the possible association
      requires further research.

PMID- 25858376
TI  - [Expression and clinical significance of the genes of Wnt signaling pathway in
      keratocystic odontogenic tumor of the jaw bones].
AB  - PURPOSE: To study the role of genes of Wnt signaling pathway in keratocystic
      odontogenic tumor (KCOT) of the jaw bones. METHODS: Fresh specimens of KCOT and
      the same patient 's normal oral mucosa were obtained. Then RNA was extracted.
      Gene chip was used to detect the genes of Wnt signaling pathway. RESULTS:
      Compared to normal oral mucosa, there were 5 genes of Wnt signaling pathway in
      KCOT changed, including CAMK2A down-regulated, FZD3, MAPK10, PRKX and WNT5a up
      regulated. CONCLUSIONS: There are abnormal expressions of genes of Wnt pathway in
      KCOT. Genes of Wnt pathway plays certain roles in KCOT.

PMID- 25858377
TI  - [Investigation of the prevalence of periodontal diseases among naval personnel
      during prolonged sailing].
AB  - PURPOSE: To investigate the prevalence of periodontal diseases among naval
      personnel during prolonged sailing. METHODS: The calculus index-simplified (CI
      S), plaque index (PLI), gingival index (GI), community periodontal index (CPI),
      attachment loss (AL), number of missing tooth (NMT) and prevalence of periodontal
      disease were recorded among 186 naval personnel who participated in prolonged
      sailing before and after sailing. The data was analyzed with SPSS 14.0 software
      package. RESULTS: Each periodontal index after sailing was significantly higher
      than that of before sailing(P<0.01). Before sailing, the prevalence of
      periodontal diseases from 186 objects was 59.7%; While after sailing the
      prevalence increased to 83.3%. Among them, patients who suffered from gingivitis
      and mid or moderate periodontitis raised greatly, and significant differences
      were found in the prevalence and degree of periodontal disease (P<0.01) compared
      between pre-sailing and post-sailing. CONCLUSIONS: Prolonged sailing environment,
      food constraint and poor oral hygiene can influence periodontal state of naval
      personnel. To enhance propaganda and education on oral hygiene promptly and
      effectively, to develop the habit of correct toothbrushing, to have balanced and
      rational diet, and to perform proper periodontal non-surgical treatment and
      medication are essential to periodontal health of naval personnel during
      prolonged sailing.

PMID- 25858378
TI  - [Study of the influence of nodal liquefaction in measurement of the ADC value of
      OSCC metastatic lymph nodes in patients with oral squamous cell carcinoma].
AB  - PURPOSE: To study the influence of nodal liquefaction portion in the measurement
      of the ADC value of metastatic lymph nodes in patients with oral squamous cell
      carcinoma (OSCC) on DW-MRI images. METHODS: According to the postoperative
      histopathological examination results, the DW-MRI data of 25 OSCC patients was
      analyzed. The ADC values of both solid portions of metastatic lymph nodes and the
      whole metastatic lymph nodes with internal liquefaction were selected and
      measured. Further comparison between the 2 groups was processed for 2 independent
      samples t test with SPSS 17.0 software package. RESULTS: Eleven patients out of
      all cases were diagnosed with cervical lymph node metastasis, and 15 metastatic
      lymph nodes were detected, among which 8 metastatic lymph nodes had obvious
      internal liquefaction. The average ADC values of solid portions of metastatic
      lymph nodes (group SMLN) and the whole metastatic lymph nodes with internal
      liquefaction (LMLN group) ADC were (872.1 +/- 22.65) * 10-6 mm2/s (n=15) and
      (1073 +/- 16.99) * 10-6 mm2/s (n=8), respectively. Two independent samples t test
      showed statistically significant difference of ADC values between group SMLN and
      group LMLN (P<0.05). CONCLUSIONS: The internal liquefaction in OSCC metastatic
      lymph nodes can lead to an increased average ADC value. If the measurement of
      OSCC metastatic lymph nodes includes obvious liquefaction portions, it may reduce
      the diagnostic accuracy of DW-MRI for discrimination of lymph node metastasis.

PMID- 25858379
TI  - [Detection of gingipain K in the gingival crevicular fluid of orthodontic
      patients].
AB  - PURPOSE: To explore the correlation between gingipain K (Kgp) and inflammatory
      reaction of gum in the process of orthodontic treatment, and analyse the role of
      Kgp in the development of gingivitis during orthodontic treatment. METHODS:
      Totally 45 orthodontic healthy teenagers were randomly chosen for the study. The
      subgingival plaques were collected simultaneously before orthodontic treatment
      and 3 months after treatment. 16S rDNA PCR technique was used to detect
      Porphyromonas gingivalis (P.g) and Kgp. SPSS17.0 software package was used for
      statistical analysis. RESULTS: The detection rate of Kgp was 35.71% before
      orthodontic treatment and 67.86% after treatment. Positive correlation (P<0.05)
      was observed between Kgp and gingival inflammation. CONCLUSIONS: Fixed
      orthodontic appliances cause plaque accumulation, accordingly slight gingiva
      inflammation and the increament of P.gingivalis in the early stage.

PMID- 25858380
TI  - [The change of patients' psychosomatic symptoms after orthognathic surgery].
AB  - PURPOSE: To assess the change of patients' psychological status before and after
      orthognathic surgery. METHODS: The psychological status in 36 patients were
      assessed before and after orthognathic surgery using the SCL-90 questionnaire.
      The patients were allowed to evaluate the changes of mastication, facial
      aesthetics, pronunciation and function of temporomandibular joint subjectively
      through the questionnaire. The data were analyzed using SPSS13.0 software
      package. RESULTS: Six factors including obsessive-compulsive symptoms,
      interpersonal sensitivity, depression, anxiety, phobic anxiety and psychoticism
      were significantly higher than norm preoperatively. No obvious abnormalities were
      found 2 years after operation. The self-evaluated quotas by patients after
      operation were significantly improved compared with those preoperatively.
      CONCLUSIONS: The patients' psychosomatic symptoms are significantly improved
      after operation. No significant difference is found compared with ordinary people
      concerning psychological health.

PMID- 25858381
TI  - [The influence of lower vertical dimension construction of complete denture on
      cerebral blood flow].
AB  - PURPOSE: To investigate the influence of lower vertical dimension construction on
      cerebral blood flow among patients with complete denture. METHODS: Ten edentulous
      patients were chosen and lower vertical dimension was constructed with complete
      denture. Transcranial Doppler ultrasonography was used to detect the average peak
      flow velocity, peak systolic velocity and end-diastolic peak flow velocity of the
      middle cerebral artery. The detection was performed before chewing, 10 minutes
      after chewing and 20 minutes after chewing, respectively. Before-after self
      control study was designed, and SPSS18.0 software package was used to analyze the
      data with independent samples t test and multiple comparisons and analysis of
      variance. RESULTS: There was no significant increase in cerebral blood flow
      before chewing, 10 minutes after chewing and 20 minutes after chewing in the
      experimental group, while blood flow velocity of the control group was
      significantly increased. The blood flow velocity of the experimental group 10
      minutes after chewing was significantly lower than that of the control group,
      while no significant difference was found after chewing between the experimental
      group and control group 20 minutes. CONCLUSIONS: No significant increase of
      cerebral blood flow is detected in patients whose vertical dimension are lower
      when restored with complete denture during mastication.

PMID- 25858382
TI  - [Management of infected fractures of the mandible by open reduction and rigid
      internal fixation with reconstructive plates].
AB  - PURPOSE: To evaluate the epidemiology and the treatment of infected fractures of
      the mandible. METHODS: Thirty-five cases of infected mandible fractures treated
      by extra oral open reduction and rigid internal fixation with reconstructive
      plates were retrospectively investigated. RESULTS: The fracture healing and
      occlusion recovery of 34 cases were satisfied without any nonunion or deformity,
      except 1 case healed after bone grafting for bone defect. CONCLUSIONS: The
      reconstructive plate fixation is applicable to the treatment of infected mandible
      fractures by its excellent stability and reliability.

PMID- 25858383
TI  - [Application of baked plastic splint in occlusal reconstruction: clinical
      analysis of 21 consecutive cases].
AB  - PURPOSE: To observe the effect of removable denture with metal stent of baked
      plastic occlusal pad in the reconstruction of dentition defects accompanied with
      severe residual teeth attrition. METHODS: Twenty one patients were selected with
      dentition defects accompanied with severe residual teeth attrition, who needed
      occlusal reconstruction. Their removable dentures with metal stent of baked
      plastic occlusal pad were reconstructed, and their occlusal vertical dimensions
      were restored. The restoration effect was evaluated. RESULTS: Twenty-one patients
      were treated and followed up for 12-24 months. Excellent results were achieved in
      18 patients, and fair results were obtained in 3 patients. CONCLUSIONS: Using the
      baked plastic occlusal pad can not only recover patients' occlusal vertical
      dimension, but also restore the shapes and function of their residual teeth to a
      better extent. It is a good method for occlusal reconstruction.

PMID- 25858384
TI  - [Application of role play in cardiopulmonary resuscitation teaching for dental
      students].
AB  - PURPOSE: To explore the effect of role-play in cardiopulmonary resuscitation
      (CPR) teaching for dental students. METHODS: The experimental group included 40
      students from grade 2011 while the control group included 41 students from grade
      2010 in College of Stomatology, Shanghai Jiao Tong University. Students in the
      control group were taught in traditional method, while those in the experimental
      group were taught using role play method. At the end of the course, we compared
      the outcome of theoretic test and skill evaluation about CPR. Evaluation of role
      play in the experimental group was conducted by questionnaire survey. SPSS13.0
      software package was used for statistical analysis. RESULTS: The results of
      theoretic test and skill evaluation in the experimental group were significantly
      better than those of the control group (P<0.05). The result of questionnaire
      showed that role-play was approved by over 80% students. CONCLUSIONS: Role-play
      is advantageous over traditional teaching for dental students and can improve
      students' comprehensive ability and CPR skill.

PMID- 25858385
TI  - [Research progress of quantitative DNA analysis in oral carcinoma and
      precancerous lesions].
AB  - Normal individual cells had 23 pairs of chromosome and stable DNA content. DNA
      content was varied during malignant transformation, which was specific feature of
      tumor. Quantitative DNA analysis can reflect cellular physiological or
      pathological condition by nuclear DNA content, which had significant role in
      early diagnosis, predication of prognosis and treatment selection. This article
      summarized the research progress of quantitative DNA analysis in oral carcinoma
      and precancerous lesions in recent years.

PMID- 25858386
TI  - [Three-dimensional localization and assessment of maxillary palatal impacted
      canines with cone-beam computed tomography].
AB  - PURPOSE: To evaluate the location of maxillary palatal impacted canines and
      resorption of neighboring incisors with cone-beam computed tomography (CBCT).
      METHODS: Twenty-two healthy adolescent patients who had received orthodontic
      treatments at Stomatological Hospital of Nanjing Medical University were selected
      and scanned by CBCT. Palatal impacted maxillary canines were reconstructed by
      Dolphin imaging 11.0 software. The impactions, spatial relationships and
      classification relative to adjacent structures and incisor resorption were
      assessed. RESULTS: Most of the maxillary palatal impacted canines inclinated
      mesially and palatally. Mesial malpositions were more significantly prevalent in
      Class I and IV, and the prevalence rates were 30.8% and 38.5% respectively.
      Mesial inclinations of the impacted canines to occlusal plane were mostly between
      53.8 degrees  and 68.5 degrees , and the distances from the impacted canines to
      median sagittal plane were between 5.4 and 8.4 mm. Older the patient was, further
      the impacted canines mesiopalatal displaced and mesial inclined. The roots of
      84.6% of lateral incisors and 19.2% of central incisors contacted impacted
      canines; Root resorption occurred in 50% of lateral incisors and 15.4% of central
      incisors, which predominantly located in apical third of the lateral incisors and
      middle third of the central incisors. A inverse correlation was found between the
      resorption rates of adjacent incisors and minimum distances from impacted canines
      to adjacent incisors. CONCLUSIONS: CBCT allows three dimensional evaluation of
      impaction and spatial relationships relative to adjacent structures. In addition,
      3 dimensional measurement contributes to more accurate exhibition of the adjacent
      root resorptions, inclinations and depths of the impacted canines, which leads to
      more efficient guidance of maxillary palatal impacted canines treatment.

PMID- 25858387
TI  - Getting the education model right.

PMID- 25858389
TI  - Call for mental health training to help staff support young people.

PMID- 25858390
TI  - Framework on decision making about end of life care updated.

PMID- 25858391
TI  - Best foot forward to climb Mount Kilimanjaro.

PMID- 25858392
TI  - Construction on two radiotherapy centres to begin this summer.

PMID- 25858393
TI  - Caution greets new model of education.

PMID- 25858394
TI  - Child health is low down the election agenda.

PMID- 25858399
TI  - Research essentials.

PMID- 25858400
TI  - Research and commentary. Identifying clearer healthcare pathways for adolescents
      who self-harm.

PMID- 25858402
TI  - Starting out--Take up the challenge.

PMID- 25858405
TI  - Nothing to fear with mental health.

PMID- 25858406
TI  - Opportunistic health promotion among overweight children.
AB  - AIM: To explore children's nurses' attitudes to providing health promotion advice
      to overweight children and their families during hospital admissions. METHODS:
      Individual semi-structured interviews were conducted in a private room in the
      ward setting. Interviews were recorded and transcribed, and thematic analysis of
      the transcripts was undertaken. FINDINGS: The six themes generated from responses
      were: responsibility for health promotion; sensitivity of the topic; long-term
      benefits; parents--a barrier; need for training; and need for institutional
      support. CONCLUSION: Further research with acute care children's nurses in the UK
      is required to validate the study findings. More work is also needed to explore
      the ethics of health promotion in the acute care setting.

PMID- 25858407
TI  - Training to raise staff awareness about safeguarding children.
AB  - To improve outcomes for children and young people health organisations are
      required to train all staff in children's safeguarding. This creates difficulties
      for large complex organisations where most staff provide services to the adult
      population. Heart of England NHS Foundation Trust is a large acute and community
      trust that had difficulties in engaging staff in children's safeguarding
      training. Compliance rates for clinical staff who were trained in children's
      safeguarding were low and needed to be addressed. This article sets out why
      safeguarding training is important for all staff and how the trust achieved staff
      engagement and improved compliance rates. To evaluate, maintain and develop
      safeguarding knowledge, understanding, skills, attitude and behaviour further
      resources are planned to allow access to learning resources in a variety of
      formats. 

PMID- 25858408
TI  - A randomised controlled trial examining the effectiveness of cartoons as a
      distraction technique.
AB  - AIM: Distress and pain associated with immunisation are significant problems for
      children, carers and healthcare professionals. This study was designed to
      determine whether distraction by watching cartoons during immunisation could
      reduce the distress and pain perceived by the children. METHODS: A sample of 35
      six year olds was randomly assigned to one of two groups: the first was
      distracted by standard techniques during immunisation, the second by watching
      cartoons. Levels of distress were measured with the amended observation scale of
      behavioural distress, and of pain by the Wong-Baker FACES pain rating scale.
      RESULTS: The levels of distress were significantly lower in the group distracted
      by cartoons compared with children who received traditional distraction
      techniques during immunisation. CONCLUSION: By using an easy, cheap intervention,
      children's first introduction to health services can be made a positive
      experience which will decrease the number developing pre-procedural anxiety or a
      fear of needles.

PMID- 25858409
TI  - To stay or not to stay: children's nurses' experiences of parental presence
      during resuscitation.
AB  - AIM: To examine the perspectives of children's nurses about parental presence
      during resuscitation. METHODS: Semi-structured interviews were used to collect
      data from nine children's nurses, working in the same emergency department,
      followed by thematic analysis to identify common themes. FINDINGS: Nurses thought
      that parents had a negative effect on the ability of professionals caring for the
      child. However, they also recognised the negative effect parental absence can
      have on the grieving process. During resuscitation nurses struggle personally and
      professionally to decide whether parents should be present. CONCLUSION: There is
      a lack of guidance available about how to manage parental presence at the
      resuscitation of the child. Experienced children's nurses were having to 'gauge
      it every time'.

PMID- 25858410
TI  - Reflecting on 'Valuing lives and life years: anomalies, implications, and an
      alternative'.

PMID- 25858411
TI  - Unravelling adherence to prophylaxis in haemophilia: a patients' perspective.
AB  - Given the lifelong therapy in haemophilia patients, insight in non-adherence
      behaviour from a patient perspective is important to understand patients'
      difficulties with the following treatment recommendations. The aim of this study
      was to clarify the process underlying adherence (behaviour) to prophylactic
      treatment, from a patients' perspective. To develop a grounded theory, a
      qualitative study using individual in-depth interviews was performed to
      understand experiences, perceptions and beliefs concerning adherence to
      prophylaxis. From two Dutch treatment centres, 21 adults with haemophilia using
      prophylaxis were interviewed. Patients were asked how they experience their task
      to administer prophylaxis and how they adhere to this. The interviews were
      transcribed, coded and analysed in an iterative process, leading to the
      development of the grounded theory. Adherence was determined by the position of
      prophylaxis in life. The position of prophylaxis was determined by the perception
      of prophylaxis and the ability to exert prophylaxis. Patients' perception was
      influenced by two main factors: acceptance of haemophilia and feeling/fearing
      symptoms. The ability to exert prophylaxis was influenced by understanding
      haemophilia and prophylaxis and planning/infusion skills. The combination of
      different perceptions and skills led to four main positions of prophylaxis in
      life: (i) prophylaxis integrated in life, (ii) prophylaxis according to doctors'
      advice, struggling with irregular situations, (iii) prophylaxis is too much to
      handle, (iv) prophylaxis is a confrontation with illness. The adherence level
      gradually decreased from position 1 to 4. This information can be used to design
      tailored interventions to promote adherence. 

PMID- 25858412
TI  - Mechanisms of tolvaptan-induced toxicity in HepG2 cells.
AB  - Tolvaptan, a vasopressin receptor 2 antagonist used to treat hyponatremia, has
      recently been reported to be associated with an increased risk of liver injury.
      In this study, we explored the underlying mechanisms of hepatotoxicity of
      tolvaptan using human HepG2 cells. Tolvaptan inhibited cell growth and caused
      cell death in a concentration- and time-dependent manner. Tolvaptan treatment led
      to delayed cell cycle progression, accompanied by decreased levels of several
      cyclins and cyclin-dependent kinases. Tolvaptan was found to cause DNA damage, as
      assessed by alkaline comet assays; this was confirmed by increased levels of 8
      oxoguanine and phosphorylation of histone H2AX. Exposure of HepG2 cells to
      tolvaptan enhanced cytochrome C release and triggered apoptosis by modulating Bcl
      2 family members. The activation of p38 contributed to tolvaptan-mediated
      apoptosis via down-regulation of Bcl-2. Proteasome inhibition altered tolvaptan
      induced cell cycle deregulation and enhanced tolvaptan-induced apoptosis and
      cytotoxicity. Moreover, tolvaptan treatment induced autophagy. Inhibition of
      autophagy by knocking-down an autophagy-related gene increased tolvaptan-induced
      apoptosis and cytotoxicity. Taken together, our findings suggest that the
      cytotoxicity of tolvaptan results from delayed cell cycle progression, the
      induction of DNA damage, and the execution of apoptosis. In addition, a number of
      signaling pathways were perturbed by tolvaptan and played an important role in
      its cytotoxicity. 

PMID- 25858413
TI  - A functional polymorphism in the interleukin-1beta and severity of nicotine
      dependence in male schizophrenia: a case-control study.
AB  - Previous studies have shown that the functional 511C/T polymorphism in the IL
      1beta-gene may be implicated in the susceptibility for schizophrenia. Moreover,
      recent studies suggested that IL-1 participates in the progression of lung
      disease in smokers, which are overrepresented in schizophrenia. We aimed to
      investigate the possible relationship between the IL-1beta-511C/T polymorphism
      and smoking behavior in schizophrenia versus healthy controls in a Chinese
      population. The IL-1beta-511C/T polymorphism was genotyped in 638 male patients
      with chronic schizophrenia (smoker/never-smoker = 486/152) and 469 male controls
      (smoker/never-smoker = 243/226). The cigarettes smoked per day, the Heaviness of
      Smoking Index (HSI) and the Fagerstrom Test for nicotine dependence (FTND) were
      assessed. Patients were also rated on the Positive and Negative Syndrome Scale
      (PANSS). The results showed no significant differences in genotype and allele
      distribution between patients and controls, and between smokers and never-smokers
      in either the patient or control group. However, in patients, smokers with the
      C/C genotype had significantly higher HSI (p < 0.005) and FTND (p < 0.05) scores
      than smokers with the T/T genotype, without significant differences in controls.
      Furthermore, there was a linear positive correlation between the number of C
      alleles and the HSI (p < 0.005) in patients. Our findings suggest that the IL
      1beta-511C/T polymorphism may not be related to schizophrenia or smoking status
      in Chinese individuals, but may affect the severity of nicotine dependence among
      male smokers with schizophrenia. 

PMID- 25858414
TI  - A dimensional liability model of age differences in mental disorder prevalence:
      evidence from a national sample.
AB  - Recent theories have proposed a metastructure that organizes related mental
      disorders into broad dimensions of psychopathology (i.e., internalizing and
      externalizing dimensions). Prevalence rates of most mental disorders, when
      examined independently, are substantially lower in older than in younger adults,
      which may affect this metastructure. Within a nationally representative sample,
      the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC; N =
      43,093), we developed a dimensional liability model of common psychiatric
      disorders to clarify whether aging affects specific disorders or general
      dimensions of psychopathology. Significant age differences existed across age
      groups (18-24, 25-34, 35-44, 45-54, 55-64, 65-75 and 75+), such that older adults
      showed lower prevalence rates of most disorders compared to younger adults. We
      next investigated patterns of disorder comorbidity for past-year psychiatric
      disorders and found that a distress-fear-externalizing liability model fit the
      data well. This model was age-group invariant and indicated that the observed
      lower prevalence of mental disorders with advancing age originates from lower
      average means on externalizing and internalizing liability dimensions. This
      unifying dimensional liability model of age and mental disorder comorbidity can
      help inform the role of aging on mental disorder prevalence for research and
      intervention efforts, and service planning for the impending crisis in geriatric
      mental health. 

PMID- 25858416
TI  - Self-templated chemically stable hollow spherical covalent organic framework.
AB  - Covalent organic frameworks are a family of crystalline porous materials with
      promising applications. Although active research on the design and synthesis of
      covalent organic frameworks has been ongoing for almost a decade, the mechanisms
      of formation of covalent organic frameworks crystallites remain poorly
      understood. Here we report the synthesis of a hollow spherical covalent organic
      framework with mesoporous walls in a single-step template-free method. A detailed
      time-dependent study of hollow sphere formation reveals that an inside-out
      Ostwald ripening process is responsible for the hollow sphere formation. The
      synthesized covalent organic framework hollow spheres are highly porous (surface
      area ~1,500 m(2 )g(-1)), crystalline and chemically stable, due to the presence
      of strong intramolecular hydrogen bonding. These mesoporous hollow sphere
      covalent organic frameworks are used for a trypsin immobilization study, which
      shows an uptake of 15.5 MUmol g(-1) of trypsin. 

PMID- 25858415
TI  - Generation of a safe and effective live viral vaccine by virus self-attenuation
      using species-specific artificial microRNA.
AB  - Vaccination with live attenuated vaccines (LAVs) is an effective way for
      prevention of infectious disease. While several methods are employed to create
      them, efficacy and safety are still a challenge. In this study, we evaluated the
      feasibility of creating a self-attenuated RNA virus expressing a functional
      species-specific artificial microRNA. Using influenza virus as a model, we
      produced an attenuated virus carrying a mammalian-specific miR-93 expression
      cassette that expresses a viral nucleoprotein (NP)-specific artificial microRNA
      from an insertion site within the non-structural (NS) gene segment. The resulting
      engineered live-attenuated influenza virus, PR8-amiR-93NP, produced mature and
      functional artificial microRNA against NP in mammalian cells, but not in avian
      cells. Furthermore, PR8-amiR-93NP was attenuated by 10(4) fold in mice compared
      with its wild-type counterpart. Importantly, intranasal immunization with PR8
      amiR-93NP conferred cross-protective immunity against heterologous influenza
      virus strains. In short, this method provides a safe and effective platform for
      creation of live attenuated RNA viral vaccines. 

PMID- 25858417
TI  - [Accreditation of a hygiene hospital laboratory for sampling and analysis
      activities for the detection and counting of Legionella in water].
AB  - Since January 1(st) 2012, detection and counting of Legionella bacteria have been
      obligatory in France and must be carried out by COFRAC-accredited laboratories.
      In our establishment, sampling and analysis were outsourced and our hospital was
      scheduled to move to a new site. We aimed to develop both these activities in
      house and to obtain COFRAC accreditation, whilst organizing the move to the new
      site. We set up a quality assurance system bringing together staff from the
      hygiene laboratory and institutional resource managers. We set up sampling and
      analysis activities in-house 13 months before requesting accreditation. The
      initial evaluation took place before we moved and identified 17 areas of
      deficiency, six of which were considered critical. After we had moved, a
      subsequent evaluation considered 14 of these deficiencies to have been corrected,
      included the six initially identified as critical. We were therefore awarded
      accreditation. The quality assurance system established during the year before
      our request was submitted led to accreditation two and a half years after the
      transfer in-house of sampling and analysis activities, despite our hospital
      moving during this period. 

PMID- 25858418
TI  - Polychaete burrows harbour distinct microbial communities in oil-contaminated
      coastal sediments.
AB  - Previous studies have shown that the bioturbating polychaete Hediste (Nereis)
      diversicolor can affect the composition of bacterial communities in oil
      contaminated sediments, but have not considered diversity specifically within
      bioturbator burrows or the impact on microbial eukaryotes. We tested the
      hypothesis that H. diversicolor burrows harbour different eukaryotic and
      bacterial communities compared with un-bioturbated sediment, and that
      bioturbation stimulates oil degradation. Oil-contaminated sediment was incubated
      with or without H. diversicolor for 30 days, after which sediment un-affected by
      H. diversicolor and burrow DNA/RNA samples were analysed using quantitative
      reverse transcription PCR (Q-RT-PCR) and high-throughput sequencing. Fungi
      dominated both burrow and un-bioturbated sediment sequence libraries; however,
      there was significant enrichment of bacterivorous protists and nematodes in the
      burrows. There were also significant differences between the bacterial
      communities in burrows compared with un-bioturbated sediment. Increased activity
      and relative abundance of aerobic hydrocarbon-degrading bacteria in the burrows
      coincided with the significant reduction in hydrocarbon concentration in the
      bioturbated sediment. This study represents the first detailed assessment of the
      effect of bioturbation on total microbial communities in oil-contaminated
      sediments. In addition, it further shows that bioturbation is a significant
      factor in determining microbial diversity within polluted sediments and plays an
      important role in stimulating bioremediation. 

PMID- 25858419
TI  - Robotic Level III Inferior Vena Cava Tumor Thrombectomy: Initial Series.
AB  - PURPOSE: Level III inferior vena cava tumor thrombectomy for renal cancer is one
      of the most challenging open urologic oncology surgeries. We present the initial
      series of completely intracorporeal robotic level III inferior vena cava tumor
      thrombectomy. MATERIALS AND METHODS: Nine patients underwent robotic level III
      inferior vena cava thrombectomy and 7 patients underwent level II thrombectomy.
      The entire operation (high intrahepatic inferior vena cava control, caval
      exclusion, tumor thrombectomy, inferior vena cava repair, radical nephrectomy,
      retroperitoneal lymphadenectomy) was performed exclusively robotically. To
      minimize the chances of intraoperative inferior vena cava thrombus embolization,
      an "inferior vena cava-first, kidney-last" robotic technique was developed. Data
      were accrued prospectively. RESULTS: All 16 robotic procedures were successful,
      without open conversion or mortality. For level III cases (9), median primary
      kidney (right 6, left 3) cancer size was 8.5 cm (range 5.3 to 10.8) and inferior
      vena cava thrombus length was 5.7 cm (range 4 to 7). Median operative time was
      4.9 hours (range 4.5 to 6.3), estimated blood loss was 375 cc (range 200 to
      7,000) and hospital stay was 4.5 days. All surgical margins were negative. There
      were no intraoperative complications and 1 postoperative complication (Clavien
      3b). At a median 7 months of followup (range 1 to 18) all patients are alive.
      Compared to level II thrombi the level III cohort trended toward greater inferior
      vena cava thrombus length (3.3 vs 5.7 cm), operative time (4.5 vs 4.9 hours) and
      blood loss (290 vs 375 cc). CONCLUSIONS: With appropriate patient selection,
      surgical planning and robotic experience, completely intracorporeal robotic level
      III inferior vena cava thrombectomy is feasible and can be performed efficiently.
      Larger experience, longer followup and comparison with open surgery are needed to
      confirm these initial outcomes.

PMID- 25858420
TI  - Low Use of Immediate and Delayed Postoperative Radiation for Prostate Cancer with
      Adverse Pathological Features.
AB  - PURPOSE: Level 1 evidence supports immediate radiation in post-prostatectomy
      patients with adverse pathological features while analogous evidence for delayed
      radiation is lacking. We evaluated immediate and delayed radiation practice
      patterns and identified factors affecting their use. MATERIALS AND METHODS: Using
      the National Cancer Data Base we identified 57,448 men diagnosed with pT3 disease
      and/or positive margins from 2004 to 2009. Postoperative radiation use through
      2011 was analyzed by time trends and multivariate analysis. RESULTS: A total of
      4,316 men (7.5%) received immediate radiation, 1,637 (2.8%) received delayed
      radiation and 51,495 (90%) were observed. Immediate and delayed radiation use
      remained relatively stable except for a small but significant decrease in
      immediate radiation in 2008. This decrease was associated with a relative
      increase in delayed radiotherapy. Compared to 2004 men diagnosed in 2007 to 2009
      had 1.3-fold to 1.5-fold higher odds of delayed radiation than of immediate
      radiation (p <0.01). The strongest predictors of immediate radiation were margin
      status, T stage, N stage, Gleason score and patient age. Men with positive
      margins, seminal vesicle invasion, nodal disease, or Gleason score 8 or greater
      and younger men had 2.3-fold to sixfold greater odds of receiving immediate
      radiation than observation (p <0.01). Men with positive margins, seminal vesicle
      invasion or nodal metastases were also more likely to receive immediate rather
      than delayed radiation (p <0.01). CONCLUSIONS: Post-prostatectomy radiation is
      performed sparingly. Immediate radiation rates remain low but do not appear to be
      influenced substantially by delayed radiation use. Consistent with the evidence,
      patients at high risk for recurrence are more likely to undergo immediate
      radiation rather than observation or delayed radiation.

PMID- 25858421
TI  - Risk Factors for Catheter Associated Urinary Tract Infections in a Pediatric
      Institution.
AB  - PURPOSE: Catheter associated urinary tract infections are an essential measure
      for health care quality improvement that affects reimbursement through hospital
      acquired condition reduction programs in adult patients. With the mounting
      importance of preventing such infections we evaluated risk factors for acquiring
      catheter associated urinary tract infections in pediatric patients. MATERIALS AND
      METHODS: All catheter associated urinary tract infections were identified at 1
      pediatric institution from September 2010 to August 2014 from a prospective
      database maintained by the infection control office. To identify risk factors
      patients with a catheter associated urinary tract infection were individually
      matched to control patients with a urinary catheter but without infection by age,
      gender, date and the hospital location of the infection in 1:2 fashion. RESULTS:
      A total of 50 patients with catheter associated urinary tract infection were
      identified and matched to 100 control patients. Compared to controls the patients
      with infection were more likely to have a catheter in place for longer (2.9 days,
      OR 1.08, 95% CI 1.01, 1.15, p = 0.02). They were also more likely to be on
      contact precautions (OR 4.00, 95% CI 1.73, 9.26, p = 0.001), and have concurrent
      infections (OR 3.04, 95% CI 1.39, 6.28, p = 0.005) and a history of
      catheterization (OR 3.24, 95% CI 1.55, 6.77, p = 0.002). Using a conditional
      multivariate regression model the 3 most predictive variables were duration of
      catheter drainage, contact isolation status and history of catheterization.
      CONCLUSIONS: Longer duration of urinary catheter drainage, positive contact
      precautions status and a history of catheterization appear to be associated with
      a higher risk of catheter associated urinary tract infection in hospitalized
      pediatric patients. Physicians should attempt to decrease the duration of
      catheterization, especially in patients who meet these criteria, to minimize the
      risk of catheter associated urinary tract infection.

PMID- 25858422
TI  - Lifestyle modifications supported by regional health nurses lowered insulin
      resistance, oxidative stress and central blood pressure in subjects with
      metabolic syndrome.
AB  - BACKGROUND: This study was attempted to investigate whether lifestyle
      modifications supported by regional health nurses should improve cardio-metabolic
      factors--including adipocytokines, oxidative stress, and arterial stiffness--in
      subjects with metabolic syndrome. METHODS: Thirty-six subjects with metabolic
      syndrome were enrolled, 28 of whom completed the 6-month lifestyle modifications
      (male:female=19:9). Blood and urine test results were examined in relation to
      metabolic factors before and after 6-month nutritional and physical activity
      modifications. In addition, oral glucose tolerance tests were performed and
      arterial stiffness was measured by brachial-ankle pulse wave velocity and radial
      augmentation index before and after them. RESULTS: Six-month lifestyle
      modifications significantly reduced body weight, homeostasis model assessment
      index, and low-density lipoprotein cholesterol (LDL-C). They significantly
      attenuated oxidative stress measured by the urinary 8-hydroxy-2
      deoxyguanosine/creatinine ratio. They also lowered brachial and central systolic
      blood pressure. They tended to decrease waist circumferences and the levels of C
      reactive protein. However they did not significantly change the levels of
      adipocytokines, including tumour necrosis factor, soluble tumour necrosis factor
      receptors, and interleukin 6, or arterial stiffness measured by brachial-ankle
      pulse wave velocity and radial augmentation index. CONCLUSIONS: Six-month
      lifestyle modifications supported by regional health nurses lowered body weight,
      insulin resistance, LDL-C, oxidative stress, and peripheral and central blood
      pressure in subjects with metabolic syndrome.

PMID- 25858423
TI  - Pursuing bariatric surgery in an urban area: Gender and racial disparities and
      risk for psychiatric symptoms.
AB  - BACKGROUND: Bariatric surgery is effective for weight loss; however, only a small
      percentage of those who qualify choose to pursue it. Additionally, although
      psychiatric symptoms appear to be common among candidates, the risk factors for
      symptoms are not known. Therefore, the purpose of this study was to examine the
      characteristics of those who are pursuing bariatric surgery in an urban area,
      whether demographic disparities continue to exist, and identify characteristics
      of those who may be at higher risk for experiencing psychiatric symptoms.
      METHODS: There were 424 bariatric candidates who completed a required
      psychological evaluation prior to bariatric surgery. RESULTS AND CONCLUSIONS:
      Bariatric surgery candidates tended to be middle-aged, Caucasian females, which
      was unexpected when compared to the rates of obesity among these groups.
      Therefore, it appears that there are disparities in who chooses to seek out
      bariatric surgery compared to those who may qualify due to their obesity status.
      Cultural factors may play a role in why males and African Americans seek out
      bariatric surgery less frequently. Psychiatric symptoms among candidates are also
      common, with depression symptoms increasing with age and BMI. Perhaps the
      compounding effects of medical comorbidities over time are contributing to
      greater depressive symptoms in the older patients. Findings from this study
      suggest that we may need to explore ways of encouraging younger patients, males,
      and ethnic minorities to pursue bariatric surgery to increase weight loss success
      and decrease medical comorbidities.

PMID- 25858424
TI  - Laryngeal dysplasia: an evidence-based flowchart to guide management and follow
      up.
AB  - BACKGROUND: Laryngeal dysplasia is an important pre-malignant lesion. In 2010, a
      consensus statement by ENT surgeons and pathologists was published outlining the
      management and follow up of patients with laryngeal dysplasia. OBJECTIVE: After
      reviewing these guidelines, we noted the need for a flowchart for laryngologists
      to improve efficiency in managing dysplasia and encourage adherence to evidence
      based protocols. RESULT: A diagram has been produced to aid other ENT units
      around the country.

PMID- 25858426
TI  - Inhibition of bcr-abl in human leukemic cells with a coiled-coil protein
      delivered by a leukemia-specific cell-penetrating Peptide.
AB  - The oncoprotein Bcr-Abl is the cause of chronic myeloid leukemia (CML).1 Current
      therapies target the tyrosine kinase domain of Bcr-Abl, but resistance to these
      drugs is common.2 Bcr-Abl homo-oligomerization via its N-terminal coiled-coil
      (CC) domain is required for tyrosine kinase activity.3 Our previous work has
      shown that it is possible to inhibit Bcr-Abl activity by targeting the CC domain
      with a peptidomemetic known as CC(mut3), delivered as a plasmid.4 In this study,
      CC(mut3) is delivered to cells as a protein by utilizing a leukemia-specific cell
      penetrating peptide (CPP).5 Here, recombinant CPP-CC(mut3) was expressed,
      purified, and tested for its antioncogenic activity. CPP-CC(mut3) was able to
      enter two leukemic cell lines (K562 and Ba/F3-P210) and inhibit Bcr-Abl activity
      as shown by induction of necrosis/apoptosis via 7-AAD/Annexin V staining,
      reduction of oncogenic potential in colony forming assays, reduction of cell
      proliferation, and inhibition of Bcr-Abl phosphorylation (kinase activity).
      Further, CPP-CC(mut3) did not enter nonleukemic cell lines (HEK293 and MCF-7).
      While CPP-CC(mut3) was able to enter the parental, nonleukemic Bcr-Abl(-) Ba/F3
      pro-B cell line, it revealed no signs of activity in the assays performed, as
      expected. These results indicate the feasibility of using CPP-CC(mut3) as a
      therapeutic against CML. 

PMID- 25858425
TI  - Akt and mitogen-activated protein kinase enhance C-type lectin-like receptor 2
      mediated platelet activation by inhibition of glycogen synthase kinase
      3alpha/beta.
AB  - BACKGROUND: The C-type lectin-like receptor 2 (CLEC-2) and the collagen receptor
      glycoprotein (GP)VI activate platelets through Src and Syk tyrosine kinases, and
      phospholipase Cgamma2. The initial events in the two signaling cascades, however,
      are distinct, and there are quantitative differences in the roles of proteins
      downstream of Syk activation. The activation of Akt and mitogen-activated protein
      kinases (MAPKs) has been shown to enhance platelet activation by GPVI, but their
      role in CLEC-2 signaling is not known. OBJECTIVES: We sought to investigate the
      role of the Akt and MAPK pathways in platelet activation by CLEC-2. RESULTS: The
      CLEC-2 agonist rhodocytin stimulated phosphorylation of Akt and p38 and
      extracellular signal-related kinase (ERK) MAPKs, but with a delay relative to
      Syk. Phosphorylation of these proteins was markedly inhibited in the combined
      presence of apyrase and indomethacin, consistent with the reported feedback
      action of ADP and thromboxane A2 in CLEC-2 signaling. Phosphorylation of Akt and
      phosphorylation of ERK were blocked by the phosphoinositide 3-kinase (PI3K)
      inhibitor wortmannin and the protein kinase C (PKC) inhibitor Ro31-8220,
      respectively, whereas Syk phosphorylation was not altered. On the other hand,
      both inhibitors reduced phosphorylation of the Akt substrate glycogen synthase
      kinase 3alpha/beta (GSK3alpha/beta). Phosphorylation of GSK3alpha/beta was also
      blocked by the Akt inhibitor MK2206, and reduced at late, but not early, times by
      the MEK inhibitor PD0325901. MK2206 and PD0325901 inhibited aggregation and
      secretion in response to a low concentration of rhodocytin, which was restored by
      GSK3alpha/beta inhibitors. CONCLUSIONS: These results demonstrate that CLEC-2
      regulates Akt and MAPK downstream of PI3K and PKC, leading to phosphorylation and
      inhibition of GSK3alpha/beta, and enhanced platelet aggregation and secretion.

PMID- 25858427
TI  - Association between regional white and gray matter volume and ambiguity
      tolerance: Evidence from voxel-based morphometry.
AB  - The concept of tolerance of ambiguity (AT) is defined as the way in which an
      individual tends to perceive and deal with confusing, vague, and unclear
      situations. AT is generally considered as an important personality trait, but the
      neural mechanisms underlying individual differences in AT have never been
      investigated. Using voxel-based morphometry and MSTAT-II scale, we investigated
      the correlations between AT and regional white matter volume (rWMV) and regional
      gray matter volume (rGMV) in 351 young healthy subjects. We found AT to be
      positively correlated with rGMV in the dorsolateral prefrontal cortex (DLPFC),
      and negatively correlated with rGMV in the precuneus. These results indicate that
      increased rGMV in the left DLPFC may lead to characteristics of ambiguous stimuli
      consideration from multiple contexts and risk taking. Decreased rGMV in the left
      precuneus may be associated with a high tolerance for ambiguity, which attributes
      uncertainty to self-related factors. 

PMID- 25858428
TI  - Versatile Conjugated Polymer Nanoparticles for High-Resolution O2 Imaging in
      Cells and 3D Tissue Models.
AB  - High brightness, chemical and photostability, tunable characteristics, and
      spectral and surface properties are important attributes for nanoparticle probes
      designed for live cell imaging. We describe a class of nanoparticles for high
      resolution imaging of O2 that consists of a substituted conjugated polymer
      (polyfluorene or poly(fluorene-alt-benzothiadiazole)) acting as a FRET antenna
      and a fluorescent reference with covalently bound phosphorescent metalloporphyrin
      (PtTFPP, PtTPTBPF). The nanoparticles prepared from such copolymers by
      precipitation method display stability, enhanced (>5-10 times) brightness under
      one- and two-photon excitation, compatibility with ratiometric and lifetime-based
      imaging modes, and low toxicity for cells. Their cell-staining properties can be
      modulated with positively and negatively charged groups grafted to the backbone.
      The "zwitter-ionic" nanoparticles show high cell-staining efficiency, while their
      cell entry mechanisms differ for the different 3D models. When injected in the
      bloodstream, the cationic and anionic nanoparticles show similar distribution in
      vivo. These features and tunable properties make the conjugated polymer based
      phosphorescent nanoparticles a versatile tool for quantitative O2 imaging with a
      broad range of cell and 3D tissue models. 

PMID- 25858429
TI  - Health-related quality of life in 794 patients with a peripheral facial palsy
      using the FaCE Scale: a retrospective cohort study.
AB  - OBJECTIVES: To describe the health-related quality of life of patients visiting a
      tertiary referral centre for facial palsy, and to analyse factors associated with
      health-related quality of life, using the FaCE Scale instrument. DESIGN:
      Retrospective cohort study. SETTING: The Facial Nerve Center at the Massachusetts
      Eye and Ear Infirmary, a tertiary referral centre. PARTICIPANTS: Patients with a
      peripheral facial palsy visiting the centre for an initial consultation between
      August 2007 and June 2012. MAIN OUTCOME MEASURES: The total FaCE score and the
      FaCE social function subdomain. Multiple regression models were developed to
      identify factors associated with the total FaCE score and FaCE social function
      score. RESULTS: A total of 794 patients with a mean age of 47.0 +/- 16.0 years
      were analysed in this study, of which 59.9% were female. The mean House
      Brackmann, Sunnybrook, total FaCE and FaCE social function scores were 3.6 +/-
      1.5, 48.2 +/- 21.2, 47.3 +/- 19.3 and 55.5 +/- 19.2, respectively. Increasing age
      (r = -0.229, P < 0.001) was associated with a lower total FaCE score. Female
      gender (r = -4.422, P = 0.033) and increased duration of palsy (r = -0.018, P =
      0.041) were associated with lower FaCE social function scores. CONCLUSIONS: While
      counselling patients on what to expect during the recovery process after facial
      paralysis is an important part of any clinical visit, FaCE score correlations
      suggest that female patients with chronic facial palsy and increased age
      constitute a patient category that may require additional time and attention to
      prevent or mitigate psychosocial dysfunction.

PMID- 25858430
TI  - Absence of intrinsic post-zygotic incompatibilities in artificial crosses between
      sympatric coregonid species from upper Lake Constance.
AB  - A full factorial crossing experiment with five females and five males of each of
      two coregonid species from upper Lake Constance was used to test for intrinsic
      post-zygotic incompatibilities during early ontogeny. Up until shortly before
      hatching, there was no difference in embryo mortality between homo and
      heterologous crosses. A maternal effect on mortality was found in both species,
      but paternal effects and female-male interactions were absent. Thus, genetic
      incompatibility during early ontogeny does not appear to prevent introgressive
      hybridization, suggesting that genetic divergence between these species is
      maintained primarily by pre-zygotic barriers. The recent genetic homogenizations
      of coregonid species flocks in European alpine lakes may have been caused by a
      flattening of adaptive landscapes through eutrophication, but intensive stocking
      with larvae obtained in hatcheries from artificially fertilized eggs is also
      likely to be a contributing factor. To safeguard diversity among sympatric
      coregonids, it is important to re-establish ecological conditions conducive to
      species divergence and to revise traditional management strategies. 

PMID- 25858431
TI  - Variations in Head-and-Face Shape of Chinese Civilian Workers.
AB  - This study aims to elucidate variations in head-and-face shape among the Chinese
      civilian workers. Most respirator manufacturers are using outdated, Western
      anthropometric data to design respirators for the Chinese workers. Therefore,
      newly acquired anthropometric data specific to the Chinese population are needed
      to create more effective personal protective equipment. The three-dimensional
      (3D) head scans of 350 participants, who were selected from the 3000 participants
      in the 2006 Chinese Anthropometric Survey, were processed using geometric
      processing techniques. Each scan was then linked with the others, making
      statistical shape analysis on a dense set of 3D points possible. Furthermore,
      this provided for the reduction of scan noise as well as for the patching of
      holes. Following general scan correspondence and fine tuning, principal component
      analysis was used to analyze the variability in head-and-face shape of the 3D
      images. More than 90% of the variability among head-and-face shapes was accounted
      for with 26 principal components. Future study is recommended so the overall
      usefulness of the point cloud-based approach for the quantification of variations
      in facial morphology may be determined. 

PMID- 25858432
TI  - Comparison and Evaluation of Multiple Users' Usage of the Exposure and Risk Tool:
      Stoffenmanager 5.1.
AB  - Stoffenmanager is an exposure and risk assessment tool that has a control banding
      part, with risk bands as outcome and a quantitative exposure assessment part,
      with the 90th percentile of the predicted exposure as a default outcome. The main
      aim of the study was to investigate whether multiple users of Stoffenmanager came
      to the same result when modelling the same scenarios. Other aims were to
      investigate the differences between outcomes of the control banding part with the
      measured risk quota and to evaluate the conservatism of the tool by testing
      whether the 90th percentiles are above the measured median exposures. We
      investigated airborne exposures at companies in four different types of industry:
      wood, printing, metal foundry, and spray painting. Three scenarios were modelled
      and measured, when possible, at each company. When modelled, 13 users visited
      each company on the same occasion creating individual assessments. Consensus
      assessments were also modelled for each scenario by six occupational hygienists.
      The multiple users' outcomes were often spread over two risk bands in the control
      banding part, and the differences in the quantitative exposure outcomes for the
      highest and lowest assessments per scenario varied between a factor 2 and 100.
      Four parameters were difficult for the users to assess and had a large impact on
      the outcome: type of task, breathing zone, personal protection, and control
      measures. Only two scenarios had a higher measured risk quota than predicted by
      the control banding part, also two scenarios had slightly higher measured median
      exposure value than modelled consensus in the quantitative exposure assessment
      part. Hence, the variability between users was large but the model performed
      well. 

PMID- 25858433
TI  - NHS is "withering away" as result of government policies, open letter from 140
      senior doctors says.

PMID- 25858435
TI  - Developments in geriatric cancer chemotherapy.

PMID- 25858434
TI  - Emerging OP354-Like P[8] Rotaviruses Have Rapidly Dispersed from Asia to Other
      Continents.
AB  - The majority of human group A rotaviruses possess the P[8] VP4 genotype.
      Recently, a genetically distinct subtype of the P[8] genotype, also known as
      OP354-like P[8] or lineage P[8]-4, emerged in several countries. However, it is
      unclear for how long the OP354-like P[8] gene has been circulating in humans and
      how it has spread. In a global collaborative effort 98 (near-)complete OP354-like
      P[8] VP4 sequences were obtained and used for phylogeographic analysis to
      determine the viral migration patterns. During the sampling period, 1988-2012, we
      found that South and East Asia acted as a source from which strains with the
      OP354-like P[8] gene were seeded to Africa, Europe, and North America. The time
      to the most recent common ancestor (TMRCA) of all OP354-like P[8] genes was
      estimated at 1987. However, most OP354-like P[8] strains were found in three main
      clusters with TMRCAs estimated between 1996 and 2001. The VP7 gene segment of
      OP354-like P[8] strains showed evidence of frequent reassortment, even in
      localized epidemics, suggesting that OP354-like P[8] genes behave in a similar
      manner on the evolutionary level as other P[8] subtypes. The results of this
      study suggest that OP354-like P[8] strains have been able to disperse globally in
      a relatively short time period. This, in combination with a relatively large
      genetic distance to other P[8] subtypes, might result in a lower vaccine
      effectiveness, underscoring the need for a continued surveillance of OP354-like
      P[8] strains, especially in countries where rotavirus vaccination programs are in
      place. 

PMID- 25858436
TI  - Is riluzole a potential therapy for Rett syndrome?
AB  - Rett syndrome (RTT) is a severe neurodevelopmental disorder with autistic
      features and is caused by loss-of-function mutations in the gene encoding methyl
      CpG-binding protein 2 (MECP2) in the majority of cases. Besides symptomatic
      treatment, no therapeutic trials have shown effectiveness for RTT. Some
      perspectives in the treatment of RTT have been provided by recent works showing a
      phenotypic reversal by increasing brain-derived neurotrophic factor (BDNF)
      expression in a RTT mouse model. Glutamate may also play an important role in the
      primary pathogenesis in Rett syndrome through the excitotoxic neuronal injury in
      experimental models. Riluzole, an agent currently approved for the treatment of
      amyotrophic lateral sclerosis, is a glutamatergic modulator and BDNF enhancer
      with neuroprotective properties. For these reasons, riluzole could potentially
      play an important role in the treatment of RTT symptoms. Several points regarding
      the use of riluzole in RTT are discussed. Further evaluation of the therapeutic
      effects of this agent in RTT animal models is needed before clinical trials can
      begin. 

PMID- 25858437
TI  - Modeling the role of osmotic forces in the cerebrovascular response to CO2.
AB  - Increases in blood osmolarity have been shown to exert a vasodilatory effect on
      cerebral and other vasculature, with accompanying increases in blood flow. It has
      also been shown that, through an influence on blood concentration of the
      bicarbonate ion and pH, changes in blood levels of CO2 can alter blood osmolarity
      sufficiently to have an impact on vessel diameter. We propose here that this
      phenomenon plays a previously unappreciated role in CO2-mediated vasodilation,
      and present a biophysical model of osmotically driven vasodilation. Our model,
      which is based on literature data describing CO2-dependent changes in blood
      osmolarity and hydraulic conductivity (Lp) of the blood-brain barrier, is used to
      predict the change in cerebral blood flow (CBF) associated with osmotic forces
      arising from a specific hypercapnic challenge. Modeled changes were then compared
      with actual CBF changes determined using arterial spin-labeling (ASL) MRI. For
      changes in the arterial partial pressure of CO2 (PaCO2) of 20 mmHg, our model
      predicted increases of 80% from baseline CBF with a temporal evolution that was
      comparable to the measured hemodynamic responses. Our modeling results suggest
      that osmotic forces could play a significant role in the cerebrovascular response
      to CO2.

PMID- 25858438
TI  - Potential of the plant Thespesia populnea in the treatment of ulcerative colitis.
AB  - CONTEXT: Thespesia populnea Sol. ex Correa (Malvaceae), an indigenous tree
      species in India, is of interest to researchers because traditionally its
      heartwood is used in the treatment of ulcer and colic pain. OBJECTIVE: To
      validate its folk use in the treatment of ulcerative colitis (UC). MATERIALS AND
      METHODS: Mice were administered intrarectal DNBS and then treated with different
      plant extracts (100 and 200 mg/kg), 30 min before and 24 and 48 h after DNBS
      infusion. Colonic mucosal injury was assessed by macroscopic and histological
      examination. Furthermore, malondialdehyde (MDA), myeloperoxidase (MPO), protease,
      and hemoglobin (Hb) contents were measured in tissue and blood samples. RESULTS:
      Administration of various extracts ameliorated macroscopic and microscopic scores
      which were altered due to DNBS treatment in mice. Hb concentration in blood was
      restored significantly by the aqueous extract to 17.20 +/- 0.5, which was reduced
      to 13.80 +/- 0.5 after treatment with DNBS. MDA level was increased to 10.82
      nm/mg and 10.25 nm/ml in tissue and blood, respectively, due to DNBS treatment
      which was reduced to 2.69 nm/mg and 3.59 nm/ml in tissue and blood, respectively,
      by aqueous extract treatment. Similarly, MPO level was increased to 412 U/mg and
      404 U/ml in tissue and blood, respectively, which was significantly reduced to
      205 U/mg and 219 U/ml in tissue and blood, respectively, by aqueous extract
      treatment. Aqueous extract significantly reduced protease activity which was
      markedly increased in DNBS-treated animals. DISCUSSION AND CONCLUSION: Aqueous
      extract of heartwood of T. populnea is effective in the treatment of UC.

PMID- 25858439
TI  - The changing landscape of cancer care - the impact of psychosocial clinical
      practice guidelines.
AB  - The International Psycho-Oncology Society (IPOS) has championed the need for
      quality care to incorporate attention to the psychosocial concerns of cancer
      patients. Widespread international endorsement of distress as the '6th vital
      sign' is a major step towards improving access to psychosocial care and reducing
      the isolation and stigma experienced by many affected by cancer. However, the
      integration of psychosocial care into routine clinical practice also requires
      active multidisciplinary engagement, and demonstration that evidence-based
      psychosocial interventions are effective and feasible to deliver in practice.
      Clinical practice guidelines are valuable in this context. Typically, they
      provide a synthesis and evaluation of existing evidence, critically appraised by
      stakeholders and clinicians, presented in a way which allows for translation of
      research evidence into practice. Such guidelines are also tools for informing and
      educating those who do not have psychosocial expertise, potentially increasing
      the status of psycho-oncology. This paper describes the background to the
      development of psychosocial clinical practice guidelines in Australia as a means
      of understanding the factors that can underpin the evolution of attitudes and
      integration of psychosocial care in oncology, and considers the current status of
      psychosocial care in Australia and internationally, including challenges for the
      future.

PMID- 25858440
TI  - Sexual issues among cervical cancer survivors: how can we help women seek help?
AB  - OBJECTIVE: Many women treated for cervical cancer (CC) report sexual complaints
      and sexual distress. It is important to assess these women's and their partners'
      sexual healthcare needs. This study aims to (a) investigate the prevalence of
      psychosexual healthcare needs and help-seeking behaviour among CC survivors, (b)
      identify the association between psychosocial variables and help-seeking
      intentions among CC survivors and (c) assess survivors' and partners' preferences
      regarding psychosexual healthcare services. METHODS: A multicentre cross
      sectional questionnaire study was conducted in a cohort of women with a history
      of CC (n=343, mean age=48.7), and their partners (n=154, mean age=50.8).
      Questions concerned professional healthcare needs, help-seeking behaviour, help
      seeking intentions and preferences regarding sexual healthcare services.
      Furthermore, the questionnaire assessed social cognitive variables related to
      help-seeking intentions. Data were analysed with multivariate linear regression
      analyses with future help-seeking intention as an outcome variable. RESULTS:
      About 51% of the women reported a need for information and/or professional help,
      although only 35% of these women had initiated a conversation with a professional
      about sexuality. Women considering sexual functioning important, expecting relief
      from seeking help, perceiving social support to seek help and having positive
      beliefs about the quality of professional psychosexual support had higher help
      seeking intentions. Women who were embarrassed to discuss sexual issues with a
      professional were less likely to seek help. Most participants would appreciate
      receiving information about sexuality and CC. CONCLUSIONS: Many CC survivors have
      psychosexual healthcare needs, although few seek professional help. Women and
      their partners should be facilitated in accessing sexual healthcare services.

PMID- 25858441
TI  - Burnout in oncology: is the situation alarming or reassuring?

PMID- 25858442
TI  - Comments on attentional bias and metacognitions in cancer survivors with high
      fear of cancer recurrence by Butow et al. (Psycho-oncology 25 Aug 2014).

PMID- 25858443
TI  - Attentional biases in cancer survivors: directions for future research.

PMID- 25858446
TI  - The Journey of Elastography: Background, Current Status, and Future Possibilities
      in Breast Cancer Diagnosis.
AB  - Elastography is a promising way to assess tissue differences regarding stiffness
      or elasticity for what was historically assessed manually by palpation. Combined
      with conventional imaging modalities (eg, ultrasonography [US]), elastography can
      potentially evaluate the stiffness of a breast lesion and consequently help to
      detect malignant breast tumor from benign ones. Recent studies show that
      ultrasonographic elastography (USE) provides higher image quality compared with
      conventional B-mode US or mammography during breast cancer diagnosis, which
      eventually helps to reduce false-positive results (ie, increased specificity) and
      therefore is useful in avoiding breast biopsy. This article reviews the basics of
      elastography technique, classifications, diagnosis results obtained from clinical
      studies to date for differentiating malignant breast tumors from benign lesions,
      and its future possibilities. In addition, this article generalizes different
      elastography methods, modes, and associated imaging modalities in a simpler way
      and attempts to identify misconceptions and confusion related to existing
      elastography techniques. It also makes an effort to identify the gaps of
      information that need to be filled so that interested researchers can get an
      overall idea of elastography-based methods in a convenient way to carry out their
      research on breast elastography for prospective future applications, eg, breast
      cancer diagnosis or even in intraoperative breast tumor localization. 

PMID- 25858445
TI  - Functional connectivity with distinct neural networks tracks fluctuations in
      gain/loss framing susceptibility.
AB  - Multiple large-scale neural networks orchestrate a wide range of cognitive
      processes. For example, interoceptive processes related to self-referential
      thinking have been linked to the default-mode network (DMN); whereas
      exteroceptive processes related to cognitive control have been linked to the
      executive-control network (ECN). Although the DMN and ECN have been postulated to
      exert opposing effects on cognition, it remains unclear how connectivity with
      these spatially overlapping networks contribute to fluctuations in behavior.
      While previous work has suggested the medial-prefrontal cortex (MPFC) is involved
      in behavioral change following feedback, these observations could be linked to
      interoceptive processes tied to DMN or exteroceptive processes tied to ECN
      because MPFC is positioned in both networks. To address this problem, we employed
      independent component analysis combined with dual-regression functional
      connectivity analysis. Participants made a series of financial decisions framed
      as monetary gains or losses. In some sessions, participants received feedback
      from a peer observing their choices; in other sessions, feedback was not
      provided. Following feedback, framing susceptibility-indexed as the increase in
      gambling behavior in loss frames compared to gain frames-was heightened in some
      participants and diminished in others. We examined whether these individual
      differences were linked to differences in connectivity by contrasting sessions
      containing feedback against those that did not contain feedback. We found two key
      results. As framing susceptibility increased, the MPFC increased connectivity
      with DMN; in contrast, temporal-parietal junction decreased connectivity with the
      ECN. Our results highlight how functional connectivity patterns with distinct
      neural networks contribute to idiosyncratic behavioral changes.

PMID- 25858447
TI  - Native language experience shapes neural basis of addressed and assembled
      phonologies.
AB  - Previous studies have suggested differential engagement of addressed and
      assembled phonologies in reading Chinese and alphabetic languages (e.g., English)
      and the modulatory role of native language in learning to read a second language.
      However, it is not clear whether native language experience shapes the neural
      mechanisms of addressed and assembled phonologies. To address this question, we
      trained native Chinese and native English speakers to read the same artificial
      language (based on Korean Hangul) either through addressed (i.e., whole-word
      mapping) or assembled (i.e., grapheme-to-phoneme mapping) phonology. We found
      that, for both native Chinese and native English speakers, addressed phonology
      relied on the regions in the ventral pathway, whereas assembled phonology
      depended on the regions in the dorsal pathway. More importantly, we found that
      the neural mechanisms of addressed and assembled phonologies were shaped by
      native language experience. Specifically, one key region for addressed phonology
      (i.e., the left middle temporal gyrus) showed greater activation for addressed
      phonology in native Chinese speakers, while one key region for assembled
      phonology (i.e., the left supramarginal gyrus) showed more activation for
      assembled phonology in native English speakers. These results provide direct
      neuroimaging evidence for the effect of native language experience on the neural
      mechanisms of phonological access in a new language and support the assimilation
      accommodation hypothesis. 

PMID- 25858448
TI  - Improved estimation of myelin water fraction using complex model fitting.
AB  - In gradient echo (GRE) imaging, three compartment water modeling (myelin water,
      axonal water and extracellular water) in white matter has been demonstrated to
      show different frequency shifts that depend on the relative orientation of fibers
      and the B0 field. This finding suggests that in GRE-based myelin water imaging, a
      signal model may need to incorporate frequency offset terms and become a complex
      valued model. In the current study, three different signal models and fitting
      approaches (a magnitude model fitted to magnitude data, a complex model fitted to
      magnitude data, and a complex model fitted to complex data) were investigated to
      address the reliability of each model in the estimation of the myelin water
      signal. For the complex model fitted to complex data, a new fitting approach that
      does not require background phase removal was proposed. When the three models
      were compared, the results from the new complex model fitting showed the most
      stable parameter estimation. 

PMID- 25858449
TI  - In vitro antibacterial activities of compounds isolated from roots of Caylusea
      abyssinica.
AB  - BACKGROUND: Caylusea absyssinica, a plant used as vegetable and for medicinal
      purposes was selected for in vitro antibacterial evaluation in this study. The
      main aim of this study was to isolate compounds from the plant roots and evaluate
      their antibacterial activities on clinical bacterial test strains. METHODS:
      Compounds from roots of Caylusea absyssinica (fresen) were identified based on
      observed spectral (1H-NMR, 13C-NMR and IR) data and physical properties (melting
      point) as well as reported literature. Disk diffusion method was employed to
      evaluate the antibacterial activities of the isolated compounds on four test
      bacterial strains namely, Staphylococcus aureus (ATCC25903), Escherichia coli
      (ATCC25722), Pseudomonas aeruginosa (DSMZ1117) and Salmonella thyphimurium
      (ATCC13311). RESULTS: Two compounds, CA1 and CA2 were isolated from the methanol
      crude extract of the roots of Caylusea absyssinica (fresen). The compounds were
      identified as beta-sitosterol and stigmasterol, respectively. Evaluation of
      antibacterial activities revealed that the compounds are active against all the
      bacterial strains in the experiment, showing inhibition zones ranging from 12 mm
      15 mm by CA1 and 11 mm-18 mm by CA2 against the different test strains. However,
      the compounds were less active than the reference drug (Gentamycine), which
      showed minimum inhibition zone of 21 mm (Pseudomonas aeruginosa) and maximum of
      28 mm (Escherichia coli) inhibition zone. DISCUSSION AND CONCLUSION: The
      isolation of the compounds is the first report from roots of Caylusea abyssinica
      and could be potential candidates for future antibacterial drug development
      programs.

PMID- 25858450
TI  - [Contamination of human milk with aerobic flora: Evaluation of losses for a human
      milk bank].
AB  - INTRODUCTION: In France, human milk banks pasteurize milk for the mother's own
      hospitalized baby (personalized milk) and for donation. There is specific
      legislation regulating the activity of human milk banks with bacterial screening
      of donor milk before and after pasteurization. Milk should be tested for
      Staphylococcus aureus and total aerobic flora. Any sample of milk positive for
      aerobic flora and/or S. aureus before and/or after pasteurization should be
      discarded. The real pathogenicity of the total aerobic flora is actually debated
      as well as the usefulness of systematic postpasteurization screening. The aim of
      this study was to quantify milk losses related to prepasteurization contamination
      by total aerobic flora in a regional milk bank, to identify losses due to
      contamination with S. aureus or aerobic flora, and to analyze differences between
      centers. METHODS: This was a prospective observational study conducted in the
      regional human milk bank of the Nord-Pas-de-Calais area in France. Data were
      collected from six major centers providing 80% of the milk collected between June
      2011 and June 2012. Variables were the volumes of personalized milk collected by
      each center, volumes of contaminated milk, and the type of bacteria identified.
      RESULTS: During the study period, the regional human milk bank treated 4715 L
      (liters) of personalized milk and 508 L (10.8%) were discarded due to
      bacteriological screening. Among these 508 L, 43% were discarded because of a
      prepasteurization contamination with aerobic flora, 55% because of a
      prepasteurization contamination with S. aureus, and 2% because of other
      pathogenic bacteria. Postpasteurization tests were positive in 25 samples (0.5%).
      Only five of these 25 samples were positive before pasteurization and in all
      cases with S. aureus. A total of 218 L were destroyed because of
      prepasteurization contamination with total aerobic flora, while the
      postpasteurization culture was sterile. There was a great difference between
      centers in the percentage of discarded milk and the type of contamination. The
      percentage of discarded milk varied from 4 to 16% (P<0.001) and the percentage of
      prepasteurization positive samples with aerobic flora from 0 to 70% (P<0.001).
      Costing 80 ?/L in France, this represented an economic loss of ?17,440.
      CONCLUSION: A significant volume of milk is discarded because of contamination
      with total aerobic flora found only in prepasteurization tests. Reassessment of
      the French regulations with regard to microbiological safety could save human
      milk to cover the needs of a larger group of preterm babies.

PMID- 25858452
TI  - Photocleavable ligands for protein decoration of DNA nanostructures.
AB  - This work describes the synthesis of amino-reactive, photocleavable hapten
      modifiers and their application as affinity tags for DNA nanostructures. In
      particular, N-hydroxysuccinimide-activated linkers containing an alpha-methyl
      nitroveratryl-butyric acid group and carboxyfluorescein or biotin were
      synthesized and coupled to alkyl-amino-modified DNA oligonucleotides. The
      resulting conjugates were then incorporated into DNA origami nanostructures. As
      demonstrated by electrophoresis and AFM imaging, the functionalized
      nanostructures were capable to bind cognate proteins which could then be cleaved
      off by irradiation. Owing to its modularity, this approach to control protein
      binding should be useful for a wide variety of functional DNA nanostructures. 

PMID- 25858451
TI  - [Is alfa-interferon still current in the management of Kasabach-Merritt
      syndrome?].
AB  - Kasabach-Merritt syndrome (KMS), characterized by thrombocytopenia, may
      complicate vascular tumors such as kaposiform hemangioendothelioma and tufted
      angioma. We report on two infants, respectively 2 months and 15 days old at the
      onset of symptoms, the first of whom presented with a left cervico-occipito
      scapular hemangioma with parotid extension, and the second with a vascular tumor
      located on the left shoulder with fast extension on the left inferior hemithorax
      and the left arm. Thrombocytopenia (< 20 G/L) was associated in both cases.
      Treatment comprised first high-dose corticosteroids (2mg/kg) in association with
      vincristine (1mg/m(2)/week). Interferon was introduced as third-line treatment at
      3 MIU/m(2)/day. In the first patient, interferon was effective both on
      thrombocytopenia and tumor in 2 months. In the second patient, the first
      interferon treatment was not effective despite 6 months of therapy. However, a
      second treatment 8 years later was successful. After 10 and 3 years follow-up,
      respectively, there were no side effects and most particularly no neurologic
      complications. These two observations open the discussion of the role of
      interferon (3 MIU/m(2)/day) as well as new therapies in the control of
      angiogenesis in case of failure of first-line treatment of complicated KMS
      vascular tumors.

PMID- 25858453
TI  - Insight into neonatal septicaemic Escherichia coli from India with respect to
      phylogroups, serotypes, virulence, extended-spectrum-beta-lactamases and
      association of ST131 clonal group.
AB  - The study characterizes a collection of 67 neonatal septicaemic Escherichia coli
      isolates on the basis of phylogroup, serotype, virulence, antibiotic resistance
      and also the association of CTX-M-producing E. coli and the ST131 clone in a
      developing country. Phylogroups B2 and D were predominant (33% and 19%,
      respectively). The most prevalent virulence factors (VFs) were traT (69%) and
      iucC (68%) and most VFs were concentrated in the B2 isolates. High levels of
      resistance (?70%) to cefotaxime, ciprofloxacin and trimethoprim/sulfamethoxazole
      was recorded but meropenem remained the most active antimicrobial. Six (9%) of
      the study isolates belonged to the ST131 clone, five of which were from the same
      hospital, and were either indistinguishable or closely related by pulsed-field
      gel electrophoresis. Although the prevalence of CTX-M-15-producing isolates was
      high (81%), the ST131 clone was relatively infrequent (11%) in extended spectrum
      beta-lactamase (ESBL)-producers. The ST131 clone was characterized by the
      presence of bla CTX-M-15, qnrS, aac(6')-Ib-cr, IncF plasmids and virulence
      determinants such as iucC, papC, traT, usp, hlyA, iroN E.coli , cnf, and sat. We
      conclude that clonal spread of ST131 did not contribute directly to the high
      prevalence of CTX-M-15 in our settings. 

PMID- 25858454
TI  - Structure-affinity relationship of the cocaine-binding aptamer with quinine
      derivatives.
AB  - In addition to binding its target molecule, cocaine, the cocaine-binding aptamer
      tightly binds the alkaloid quinine. In order to understand better how the cocaine
      binding aptamer interacts with quinine we have used isothermal titration
      calorimetry-based binding experiments to study the interaction of the cocaine
      binding aptamer to a series of structural analogs of quinine. As a basis for
      comparison we also investigated the binding of the cocaine-binding aptamer to a
      set of cocaine metabolites. The bicyclic aromatic ring on quinine is essential
      for tight affinity by the cocaine-binding aptamer with 6-methoxyquinoline alone
      being sufficient for tight binding while the aliphatic portion of quinine,
      quinuclidine, does not show detectable binding. Compounds with three fused
      aromatic rings are not bound by the aptamer. Having a methoxy group at the 6
      position of the bicyclic ring is important for binding as substituting it with a
      hydrogen, an alcohol or an amino group all result in lower binding affinity. For
      all ligands that bind, association is driven by a negative enthalpy compensated
      by unfavorable binding entropy. 

PMID- 25858455
TI  - Systematic synthesis and anti-inflammatory activity of omega-carboxylated
      menaquinone derivatives--Investigations on identified and putative vitamin K2
      metabolites.
AB  - Vitamin K is an essential nutrient for blood coagulation and bone homeostasis,
      and also functions in many physiological processes including inflammation and
      cancer progression. However, the nature and activities of its metabolites remain
      unclear. We report here systematic synthesis of omega-carboxylated derivatives of
      menaquinone (vitamin K2), including previously identified metabolites 5, K acid I
      (10), and K acid II (12), and evaluation of their inhibitory activity toward LPS
      stimulated induction of inflammatory cytokines. These results should contribute
      to an improved understanding of the biochemistry and pharmacology of vitamin K. 

PMID- 25858456
TI  - Control of E-cadherin apical localisation and morphogenesis by a SOAP-1/AP
      1/clathrin pathway in C. elegans epidermal cells.
AB  - E-cadherin (E-cad) is the main component of epithelial junctions in multicellular
      organisms, where it is essential for cell-cell adhesion. The localisation of E
      cad is often strongly polarised in the apico-basal axis. However, the mechanisms
      required for its polarised distribution are still largely unknown. We performed a
      systematic RNAi screen in vivo to identify genes required for the strict E-cad
      apical localisation in C. elegans epithelial epidermal cells. We found that the
      loss of clathrin, its adaptor AP-1 and the AP-1 interactor SOAP-1 induced a
      basolateral localisation of E-cad without affecting the apico-basal diffusion
      barrier. We further found that SOAP-1 controls AP-1 localisation, and that AP-1
      is required for clathrin recruitment. Finally, we also show that AP-1 controls E
      cad apical delivery and actin organisation during embryonic elongation, the final
      morphogenetic step of embryogenesis. We therefore propose that a molecular
      pathway, containing SOAP-1, AP-1 and clathrin, controls the apical delivery of E
      cad and morphogenesis. 

PMID- 25858457
TI  - Transcription factor AP-2gamma induces early Cdx2 expression and represses HIPPO
      signaling to specify the trophectoderm lineage.
AB  - Cell fate decisions are fundamental to the development of multicellular
      organisms. In mammals the first cell fate decision involves segregation of the
      pluripotent inner cell mass and the trophectoderm, a process regulated by cell
      polarity proteins, HIPPO signaling and lineage-specific transcription factors
      such as CDX2. However, the regulatory mechanisms that operate upstream to specify
      the trophectoderm lineage have not been established. Here we report that
      transcription factor AP-2gamma (TFAP2C) functions as a novel upstream regulator
      of Cdx2 expression and position-dependent HIPPO signaling in mice. Loss- and gain
      of-function studies and promoter analysis revealed that TFAP2C binding to an
      intronic enhancer is required for activation of Cdx2 expression during early
      development. During the 8-cell to morula transition TFAP2C potentiates cell
      polarity to suppress HIPPO signaling in the outside blastomeres. TFAP2C depletion
      triggered downregulation of PARD6B, loss of apical cell polarity, disorganization
      of F-actin, and activation of HIPPO signaling in the outside blastomeres. Rescue
      experiments using Pard6b mRNA restored cell polarity but only partially corrected
      position-dependent HIPPO signaling, suggesting that TFAP2C negatively regulates
      HIPPO signaling via multiple pathways. Several genes involved in regulation of
      the actin cytoskeleton (including Rock1, Rock2) were downregulated in TFAP2C
      depleted embryos. Inhibition of ROCK1 and ROCK2 activity during the 8-cell to
      morula transition phenocopied TFAP2C knockdown, triggering a loss of position
      dependent HIPPO signaling and decrease in Cdx2 expression. Altogether, these
      results demonstrate that TFAP2C facilitates trophectoderm lineage specification
      by functioning as a key regulator of Cdx2 transcription, cell polarity and
      position-dependent HIPPO signaling. 

PMID- 25858458
TI  - Hierarchical differentiation competence in response to retinoic acid ensures stem
      cell maintenance during mouse spermatogenesis.
AB  - Stem cells ensure tissue homeostasis through the production of differentiating
      and self-renewing progeny. In some tissues, this is achieved by the function of a
      definitive stem cell niche. However, the mechanisms that operate in mouse
      spermatogenesis are unknown because undifferentiated spermatogonia (Aundiff) are
      motile and intermingle with differentiating cells in an 'open' niche environment
      of seminiferous tubules. Aundiff include glial cell line-derived neurotrophic
      factor receptor alpha1 (GFRalpha1)(+) and neurogenin 3 (NGN3)(+) subpopulations,
      both of which retain the ability to self-renew. However, whereas GFRalpha1(+)
      cells comprise the homeostatic stem cell pool, NGN3(+) cells show a higher
      probability to differentiate into KIT(+) spermatogonia by as yet unknown
      mechanisms. In the present study, by combining fate analysis of pulse-labeled
      cells and a model of vitamin A deficiency, we demonstrate that retinoic acid
      (RA), which may periodically increase in concentration in the tubules during the
      seminiferous epithelial cycle, induced only NGN3(+) cells to differentiate.
      Comparison of gene expression revealed that retinoic acid receptor gamma (Rarg)
      was predominantly expressed in NGN3(+) cells, but not in GFRalpha1(+) cells,
      whereas the expression levels of many other RA response-related genes were
      similar in the two populations. Ectopic expression of RARgamma was sufficient to
      induce GFRalpha1(+) cells to directly differentiate to KIT(+) cells without
      transiting the NGN3(+) state. Therefore, RARgamma plays key roles in the
      differentiation competence of NGN3(+) cells. We propose a novel mechanism of stem
      cell fate selection in an open niche environment whereby undifferentiated cells
      show heterogeneous competence to differentiate in response to ubiquitously
      distributed differentiation-inducing signals. 

PMID- 25858459
TI  - Quantitative analysis of tissue deformation dynamics reveals three characteristic
      growth modes and globally aligned anisotropic tissue deformation during chick
      limb development.
AB  - Tissue-level characterization of deformation dynamics is crucial for
      understanding organ morphogenetic mechanisms, especially the interhierarchical
      links among molecular activities, cellular behaviors and tissue/organ
      morphogenetic processes. Limb development is a well-studied topic in vertebrate
      organogenesis. Nevertheless, there is still little understanding of tissue-level
      deformation relative to molecular and cellular dynamics. This is mainly because
      live recording of detailed cell behaviors in whole tissues is technically
      difficult. To overcome this limitation, by applying a recently developed Bayesian
      approach, we here constructed tissue deformation maps for chick limb development
      with high precision, based on snapshot lineage tracing using dye injection. The
      precision of the constructed maps was validated with a clear statistical
      criterion. From the geometrical analysis of the map, we identified three
      characteristic tissue growth modes in the limb and showed that they are
      consistent with local growth factor activity and cell cycle length. In
      particular, we report that SHH signaling activity changes dynamically with
      developmental stage and strongly correlates with the dynamic shift in the tissue
      growth mode. We also found anisotropic tissue deformation along the proximal
      distal axis. Morphogenetic simulation and experimental studies suggested that
      this directional tissue elongation, and not local growth, has the greatest impact
      on limb shaping. This result was supported by the novel finding that anisotropic
      tissue elongation along the proximal-distal axis occurs independently of cell
      proliferation. Our study marks a pivotal point for multi-scale system
      understanding in vertebrate development. 

PMID- 25858460
TI  - Diverging biological roles among human monocyte subsets in the context of
      tuberculosis infection.
AB  - Circulating monocytes (Mo) play an essential role in the host immune response to
      chronic infections. We previously demonstrated that CD16(pos) Mo were expanded in
      TB (tuberculosis) patients, correlated with disease severity and were refractory
      to dendritic cell differentiation. In the present study, we investigated whether
      human Mo subsets (CD16(neg) and CD16(pos)) differed in their ability to influence
      the early inflammatory response against Mycobacterium tuberculosis. We first
      evaluated the capacity of the Mo subsets to migrate and engage a microbicidal
      response in vitro. Accordingly, CD16(neg) Mo were more prone to migrate in
      response to different mycobacteria-derived gradients, were more resistant to M.
      tuberculosis intracellular growth and produced higher reactive oxygen species
      than their CD16(pos) counterpart. To assess further the functional dichotomy
      among the human Mo subsets, we carried out an in vivo analysis by adapting a
      hybrid mouse model (SCID/Beige, where SCID is severe combined immunodeficient) to
      transfer each Mo subset, track their migratory fate during M. tuberculosis
      infection, and determine their impact on the host immune response. In M.
      tuberculosis-infected mice, the adoptively transferred CD16(neg) Mo displayed a
      higher lung migration index, induced a stronger pulmonary infiltration of murine
      leucocytes expressing pro- and anti-inflammatory cytokines, and significantly
      decreased the bacterial burden, in comparison with CD16(pos) Mo. Collectively,
      our results indicate that human Mo subsets display divergent biological roles in
      the context of M. tuberculosis infection, a scenario in which CD16(neg) Mo may
      contribute to the anti-mycobacterial immune response, whereas CD16(pos) Mo might
      promote microbial resilience, shedding light on a key aspect of the
      physiopathology of TB disease.

PMID- 25858461
TI  - Vanadium(IV) and copper(II) complexes of salicylaldimines and aromatic
      heterocycles: Cytotoxicity, DNA binding and DNA cleavage properties.
AB  - Five copper(II) complexes, [Cu(sal-Gly)(bipy)](1), [Cu(sal-Gly)(phen)] (2),
      [Cu(sal-l-Ala)(phen)] (3), [Cu(sal-D-Ala)(phen)] (4), [Cu(sal-l-Phe)(phen)] (5)
      and five oxidovanadium(IV) complexes, [V(IV)O(sal-Gly)(bipy)] (6), [V(IV)O(sal
      Gly)(phen)] (7), [V(IV)O(sal-l-Phe)(H2O)] (8), [V(IV)O(sal-l-Phe)(bipy)] (9),
      [V(IV)O(sal-l-Phe)(phen)] (10) (sal=salicylaldehyde, bipy=2,2'-bipyridine,
      phen=1,10-phenanthroline) were synthesized and characterized, and their
      interaction with DNA was evaluated by different techniques: gel electrophoresis,
      fluorescence, UV-visible and circular dichroism spectroscopy. The complexes
      interact with calf-thymus DNA and efficiently cleave plasmid DNA in the absence
      (only 2 and 5) and/or presence of additives. The cleavage ability is
      concentration-dependent as well as metal and ligand-dependent. Moreover, DNA
      binding experiments show that the phen-containing Cu(II) and V(IV)O compounds
      display stronger DNA interaction ability than the corresponding bipy analogues.
      The complexes present cytotoxic activity against human ovarian (A2780) and breast
      (MCF7) carcinoma cells. Cell-growth inhibition (IC50) of compounds 1, 2 and 5 in
      human promyelocytic leukemia (HL60) and human cervical cancer (HeLa) cells were
      also determined. The copper complexes show much higher cytotoxic activity than
      the corresponding vanadium complexes and the reference drug cisplatin (except for
      the sal-Gly complexes); namely, the phenanthroline copper complexes 2-5 are ca.
      10-fold more cytotoxic than cisplatin and more cytotoxic than their bipyridine
      analogues. 

PMID- 25858462
TI  - An exercise regimen prevents development paclitaxel induced peripheral neuropathy
      in a mouse model.
AB  - Peripheral neuropathy is a major, dose-limiting complication of many
      chemotherapeutic agents. Currently there is no effective method to prevent
      development of chemotherapy-induced peripheral neuropathy (CIPN). Recent studies
      have shown that exercise can improve regeneration of peripheral nerves but its
      effect in preventing peripheral neuropathy is unknown. In this study, we examined
      the effect of a rigorous treadmill exercise program that was started 1 week
      before administration of paclitaxel and continued throughout the study in a mouse
      model of CIPN. We showed that exercise can partially abrogate features of axonal
      degeneration induced by paclitaxel including reduction in epidermal nerve fiber
      density in the plantar hind paw and thermal hypoalgesia. Furthermore,
      detyrosinated tubulin that is elevated in nerves treated with paclitaxel was
      normal in exercised animals. This study points to a relatively simple and
      potentially effective therapeutic option to reduce the neurotoxic effects of
      chemotherapy. 

PMID- 25858463
TI  - Consensus about managing gastrointestinal and cardiovascular risks of
      nonsteroidal anti-inflammatory drugs?
AB  - In a recently published article in BMC Medicine, Scarpignato and colleagues
      present the results of a consensus conference that addressed several aspects of
      the management of pain in patients with osteoarthritis. The main areas covered
      include the relative safety in regard to gastrointestinal and cardiovascular
      adverse events of non-selective 'traditional' non-steroidal anti-inflammatory
      drugs (NSAIDs) versus cyclooxygenase-2 selective NSAIDs. The role of co-therapy
      with proton pump inhibitors in enhancing gastrointestinal safety is also
      reviewed. This commentary focuses on two areas that the consensus conference
      addressed, i) the whole length of gastrointestinal tract risk profile of the
      various NSAIDs (not just the ulcer risks in stomach and duodenum); ii) more
      recent information, but still some uncertainties, about the cardiovascular risks
      associated with the two classes of NSAID in general, and naproxen in particular.
      Please see related article: http://dx.doi.org/10.1186/s12916-015-0285-8.

PMID- 25858468
TI  - Neuroproteomics: applications in neuroscience and neurology.

PMID- 25858469
TI  - Effect of sertraline on Ca2+ fluxes in rabbit corneal epithelial cells.
AB  - The effect of sertraline, a selective serotonin reuptake inhibitor (SSRI), on
      cytosolic free Ca2+ concentrations ([Ca2+](i)) in a rabbit corneal epithelial
      cell line (SIRC) is unclear. This study explored whether sertraline changed basal
      [Ca2+](i) levels in suspended SIRC cells by using fura-2 as a Ca2+-sensitive
      fluorescent dye. Sertraline at concentrations between 10-100 MUM increased
      [Ca2+](i) in a concentration-dependent manner. The Ca2+ signal was reduced by 23%
      by removing extracellular Ca2+. Sertraline induced Mn2+ influx, leading to quench
      of fura-2 fluorescence, suggesting Ca2+ influx. This Ca2+ influx was inhibited by
      phospholipase A2 inhibitor aristolochic acid, but not by store-operated Ca2+
      channel blockers and protein kinase C/A modulators. In Ca2+-free medium,
      pretreatment with the endoplasmic reticulum Ca2+ pump inhibitor thapsigargin,
      cyclopiazonic acid or 2,5-di-tert-butylhydroquinone greatly inhibited sertraline
      induced Ca2+ release. Inhibition of phospholipase C with U73122 abolished
      sertraline-induced [Ca2+](i) rise. At concentrations of 5-50 MUM, sertraline
      killed cells in a concentration-dependent manner. The cytotoxic effect of 25 MUM
      sertraline was not reversed by prechelating cytosolic Ca2+ with BAPTA/AM.
      Collectively, in SIRC cells, sertraline induced [Ca2+](i) rises by causing
      phospholipase C-dependent Ca2+ release from the endoplasmic reticulum and Ca2+
      influx via phospholipase A2-sensitive Ca2+ channels. Sertraline-caused
      cytotoxicity was mediated by Ca2+-independent pathways.

PMID- 25858470
TI  - Induction of survivin inhibition, G2/M cell cycle arrest and autophagic on cell
      death in human malignant glioblastoma cells.
AB  - Chemotherapy efficacy is limited by intrinsic and acquired resistance in
      glioblastoma (GBM); hence, novel tactics are crucial. Survivin has been
      demonstrated as a key resistant factor in GBM because of its function in
      inhibiting apoptosis, regulating autophagy, and in promoting G2/M cell cycle
      transition. Parthenolide has been reported to be an effective antitumor agent in
      a variety of tumor cells and decreases survivin level in leukemia cells. But the
      effect of parthenolide on survivin and the cell death process in GBM is still
      unknown. The aim of this study was to examine whether parthenolide had the
      potential to inhibit cell proliferation in the GBM cell line U373. The
      parthenolide-induced effects in relation to survivin suppression and cell death
      were further investigated. Our results showed that parthenolide substantially
      inhibited cell viability with IC50 values of approximate 16 MUM. Treatment with
      parthenolide at the dose of 16 MUM led to considerable downregulation of
      survivin, G2/M cell cycle arrest and Chk2 upregulation in cells. Parthenolide
      induced apoptosis in only a few cells and a slight increase in activated caspases
      3 levels. By contrast, parthenolide induced a significant increase of
      intracellular autophagosomes and the expression of autophagy related proteins,
      including ULK1 and LC3 I/LC3 II, in the treated cells. These results suggested
      that parthenolide induced survivin inhibition, G2/M cell cycle arrest, and
      triggered cell death through autophagic cell death in the GBM cell line. 

PMID- 25858471
TI  - Neuroprotective effects of an aqueous extract of Futokadsura stem in an Abeta
      induced Alzheimer's disease-like rat model.
AB  - Futokadsura stem has been traditionally used to dispel wind-damp obstruction
      syndrome manifested as painful and stiff joints, tendon and muscle spasms, lower
      back pain, painful knees and pain from external injury. An aqueous extract of
      Futokadsura stem has previously been found to have neuro-protective effects in
      vitro. In this study, we aimed to investigate if the Futokadsura stem extract
      could protect the neuron in the brain of an Abeta-induced Alzheimer's Disease
      (AD)-like rat model by improving the learning and memory ability of the rats.
      Learning and memory ability of the rats were measured by the Morris water maze
      test. Neuronal morphology in the hippocampus was examined by HE staining.
      Expression levels of Abeta, TNF-alpha, IL-6 and synaptophysin (SYP) were measured
      by immunofluorescence. Nitric oxide (NO) and nitric oxide synthase (NOS) levels
      were measured by NO and NOS detecting kit. We found that aqueous extract of
      Futokadsura stem alleviated Abeta(25-35)-induced impairment of spatial learning
      and memory in the AD rats. Furthermore, the extract protected the neurons by
      decreasing the expression of Abeta, TNF-alpha and IL-6 and the content of NO and
      NOS in the brain, and increasing the expression of SYP in the hippocampus. Our
      data indicated that aqueous extract of Futokadsura stem improved the learning and
      memory ability of AD rats. The neuro-protective effect was accomplished probably
      by depressing inflammation and oxidative stress in the brain. 

PMID- 25858472
TI  - Comparison of cardiac autonomic nervous system disturbed by sleep deprivation in
      sex and menstrual phase.
AB  - Sleep deprivation (SD) leads to cardiovascular risk by disturbing autonomic
      nervous system (ANS). Whether sex or menstrual cycle influences cardiac ANS
      interfered by SD remained unclear. This investigation was to further clarify the
      effects of different menstrual phases on cardiac autonomic nervous activity
      disturbed by SD. Methodologically, cardiac autonomic modulation before and after
      30 h of total SD was determined by spectral analysis of heart rate variability in
      10 healthy females during the mid-follicular (FF) and mid-luteal (FL) phases and
      10 healthy males. The result showed that before SD, the FF subjects, but not FL,
      had higher normalized high frequency (nHF) (vagal activity) or lower ratio of low
      frequency (LF) to high frequency(HF) power (sympathetic activity) while
      performing deep breathing or Valsalva maneuver (40 mmHg) than the male subjects
      did. However, the SD for 30 h in the FF group significantly increased the LF/HF
      ratio and decreased nHF level at rest and in responses to deep breathing and
      Valsalva maneuver, despite no significant change of HRV in either male or FL
      group. Simultaneously, the SD substantially lowered venous PCO2 in the FF group,
      and the decreased PCO2 level was associated with the increased LF/HF ratio
      following SD. We concluded that 30-h acute SD promotes sympathetic and depresses
      [corrected] parasympathetic activities in female during the follicular phase
      rather than the luteal phase. Compared to FF, SD-triggered cardiac sympathetic
      activation is blunted in FL. The study provides further insight into the
      physiology of acute SD in different sex and menstrual phases.

PMID- 25858474
TI  - Cell Cycle Regulation in the Estrogen Receptor Beta (ESR2)-Overexpressing Hep3B
      Hepatocellular Carcinoma Cell Line.
AB  - Epidemiological studies and experimental data have shown that the incidences of
      hepatocellular carcinoma in men are more frequent than in women. Evidence
      suggests that imbalance of hormones, including estrogen, androgen, prolactin, and
      growth hormone, modifies liver tumorigenesis. In this present study, we
      investigated how estrogen and estrogen receptor 2 (ESR2), regulates the cell
      cycle mechanism in Hep3B hepatocellular carcinoma cell line. Our results showed
      that ESR2 overexpression in the presence of 10-8 M 17-beta-estradiol
      downregulated c-myc and cyclin D1 expression and simultaneously upregulated p27
      expression. However, flow cytometry and MTT assays showed only minor G1 phase
      arrest without affecting cell viability. Taken together, these observations
      indicate that ESR2 is required to lower tumorigenesis in males by altering cell
      cycle proteins in a ligand-dependent manner. 

PMID- 25858473
TI  - Assessment of oxidative status in patients with acute kidney injury: a pilot
      study.
AB  - Extensive experimental evidence confirms the role of oxidative stress as a major
      contributor to the pathogenesis of acute kidney injury (AKI). However, less
      information is available on the evolution of prooxidant-antioxidant parameters
      from early to end-phase renal function decline in humans. This study aimed to
      determine the oxidative status in dynamic throughout the evolutionary phases of
      the disease. The study included patients with cardiovascular pathology and AKI
      hospitalized in the intensive care unit (n = 69) and age-matched healthy controls
      (n = 30). They were followed through three phases of AKI; the first [corrected]
      phase was the phase of diagnosis, which is characterized by oliguria/anuria, the
      [corrected] second phase was established diuresis, and the [corrected] third
      phase was the polyuric phase. In these phases of the disease, blood samples were
      taken from the patients for biochemical analysis. From the collected whole blood,
      we measured spectrophotometrically prooxidants: index of lipid peroxidation,
      measured as Thiobarbituric acid reactive substances (TBARS), nitrite (NO2-),
      superoxide anion radical (O2-) and hydrogen peroxide (H2O2), and antioxidants:
      activity of superoxide dismutase (SOD), catalase (CAT) and reduced glutathione
      (GSH) from erythrocyte lysate. Comparing the results of the three measurements, a
      significant difference was found in the levels of NO2- and GSH, both of which
      increased in the second phase (P < 0.05) and then decreased in the third phase,
      and a significant increase in TBARS, which was elevated in the second phase (P <
      0.05) and did not change significantly until the third phase. Our results showed
      phase-dependent modification in 3 parameters of the oxidative status (TBARS, NO2-
      and GSH). Whether these changes contribute to the deterioration of renal function
      in AKI remains to be established.

PMID- 25858475
TI  - Conservation of biodiversity through taxonomy, data publication, and
      collaborative infrastructures.
AB  - Taxonomy is the foundation of biodiversity science because it furthers discovery
      of new species. Globally, there have never been so many people involved in naming
      species new to science. The number of new marine species described per decade has
      never been greater. Nevertheless, it is estimated that tens of thousands of
      marine species, and hundreds of thousands of terrestrial species, are yet to be
      discovered; many of which may already be in specimen collections. However, naming
      species is only a first step in documenting knowledge about their biology,
      biogeography, and ecology. Considering the threats to biodiversity, new knowledge
      of existing species and discovery of undescribed species and their subsequent
      study are urgently required. To accelerate this research, we recommend, and cite
      examples of, more and better communication: use of collaborative online
      databases; easier access to knowledge and specimens; production of taxonomic
      revisions and species identification guides; engagement of nonspecialists; and
      international collaboration. "Data-sharing" should be abandoned in favor of
      mandated data publication by the conservation science community. Such a step
      requires support from peer reviewers, editors, journals, and conservation
      organizations. Online data publication infrastructures (e.g., Global Biodiversity
      Information Facility, Ocean Biogeographic Information System) illustrate gaps in
      biodiversity sampling and may provide common ground for long-term international
      collaboration between scientists and conservation organizations. 

PMID- 25858477
TI  - Adaptation of Cryo-Sectioning for IEM Labeling of Asymmetric Samples: A Study
      Using Caenorhabditis elegans.
AB  - Cryo-sectioning procedures, initially developed by Tokuyasu, have been
      successfully improved for tissues and cultured cells, enabling efficient protein
      localization on the ultrastructural level. Without a standard procedure
      applicable to any sample, currently existing protocols must be individually
      modified for each model organism or asymmetric sample. Here, we describe our
      method that enables reproducible cryo-sectioning of Caenorhabditis elegans
      larvae/adults and embryos. We have established a chemical-fixation procedure in
      which flat embedding considerably simplifies manipulation and lateral orientation
      of larvae or adults. To bypass the limitations of chemical fixation, we have
      improved the hybrid cryo-immobilization-rehydration technique and reduced the
      overall time required to complete this procedure. Using our procedures, precise
      cryo-sectioning orientation can be combined with good ultrastructural
      preservation and efficient immuno-electron microscopy protein localization. Also,
      GFP fluorescence can be efficiently preserved, permitting a direct correlation of
      the fluorescent signal and its subcellular localization. Although developed for
      C. elegans samples, our method addresses the challenge of working with small
      asymmetric samples in general, and thus could be used to improve the efficiency
      of immuno-electron localization in other model organisms. 

PMID- 25858478
TI  - Randomised clinical trial: colestyramine vs. hydroxypropyl cellulose in patients
      with functional chronic watery diarrhoea.
AB  - BACKGROUND: Idiopathic bile acid malabsorption (BAM) has been suggested as a
      cause of chronic watery diarrhoea, with a response to colestyramine in 70% of
      patients. However, the efficacy of this drug has never been investigated in
      placebo-controlled trials. AIM: To evaluate the efficacy of colestyramine as
      compared with hydroxypropyl cellulose in the treatment of functional chronic
      watery diarrhoea. METHODS: Patients with chronic watery diarrhoea were randomly
      assigned to groups given colestyramine sachets 4 g twice daily (n = 13) or
      identical hydroxypropyl cellulose sachets (n = 13) for 8 weeks. The primary end
      point was clinical remission defined as a mean of 3 or fewer stools per day
      during the week before the visit, with less than 1 watery stool per day. A
      secondary end-point was the reduction in daily watery stool number. SeHCAT test
      was performed in all patients, but an abnormal test was not a prerequisite to be
      included. RESULTS: All included patients had a SeHCAT 7-day retention <=20%.
      There were no statistical differences in the percentage of patients in clinical
      remission at week 8 between colestyramine and hydroxypropyl cellulose with either
      intention-to-treat (53.8% vs. 38.4%; P = 0.43) or per-protocol (63.6% vs. 38.4%;
      P = 0.22) analyses. However, the mean per cent decrease in watery stool number
      was significantly higher with colestyramine than with hydroxypropyl cellulose (
      92.4 +/- 3.5% vs. -75.8 +/- 7.1%; P = 0.048). The rate of adverse events related
      to study drugs did not differ between groups. CONCLUSIONS: Colestyramine (4 g
      twice daily) is effective and safe for short-term treatment of patients with
      chronic watery diarrhoea presumably secondary to BAM. Clinical Trials Register
      number EudraCT 2009-011149-14.

PMID- 25858479
TI  - Woman is sentenced to 20 years in prison for feticide after death of baby.

PMID- 25858476
TI  - Life course trajectories of alcohol consumption in the United Kingdom using
      longitudinal data from nine cohort studies.
AB  - BACKGROUND: Alcohol consumption patterns change across life and this is not fully
      captured in cross-sectional series data. Analysis of longitudinal data, with
      repeat alcohol measures, is necessary to reveal changes within the same
      individuals as they age. Such data are scarce and few studies are able to capture
      multiple decades of the life course. Therefore, we examined alcohol consumption
      trajectories, reporting both average weekly volume and frequency, using data from
      cohorts with repeated measures that cover different and overlapping periods of
      life. METHODS: Data were from nine UK-based prospective cohorts with at least
      three repeated alcohol consumption measures on individuals (combined sample size
      of 59,397 with 174,666 alcohol observations), with data spanning from adolescence
      to very old age (90 years plus). Information on volume and frequency of drinking
      were harmonised across the cohorts. Predicted volume of alcohol by age was
      estimated using random effect multilevel models fitted to each cohort. Quadratic
      and cubic polynomial terms were used to describe non-linear age trajectories.
      Changes in drinking frequency by age were calculated from observed data within
      each cohort and then smoothed using locally weighted scatterplot smoothing.
      Models were fitted for men and women separately. RESULTS: We found that, for men,
      mean consumption rose sharply during adolescence, peaked at around 25 years at 20
      units per week, and then declined and plateaued during mid-life, before declining
      from around 60 years. A similar trajectory was seen for women, but with lower
      overall consumption (peak of around 7 to 8 units per week). Frequent drinking
      (daily or most days of the week) became more common during mid to older age, most
      notably among men, reaching above 50% of men. CONCLUSIONS: This is the first
      attempt to synthesise longitudinal data on alcohol consumption from several
      overlapping cohorts to represent the entire life course and illustrates the
      importance of recognising that this behaviour is dynamic. The aetiological
      findings from epidemiological studies using just one exposure measure of alcohol,
      as is typically done, should be treated with caution. Having a better
      understanding of how drinking changes with age may help design intervention
      strategies.

PMID- 25858480
TI  - Sperm fucosyltransferase-5 mediates spermatozoa-oviductal epithelial cell
      interaction to protect human spermatozoa from oxidative damage.
AB  - Oxidative damage by reactive oxygen species (ROS) is a major cause of sperm
      dysfunction. Excessive ROS generation reduces fertilization and enhances DNA
      damage of spermatozoa. Interaction between spermatozoa and oviductal epithelial
      cells improves the fertilizing ability of and reduces chromatin damage in
      spermatozoa. Our previous data showed that oviductal epithelial cell membrane
      proteins interact with the human spermatozoa and protect them from ROS-induced
      reduction in sperm motility, membrane integrity and DNA integrity. Sperm
      fucosyltransferase-5 (sFUT5) is a membrane carbohydrate-binding protein on human
      spermatozoa. In this study, we demonstrate for the first time that sFUT5 is
      involved in human spermatozoa-oviduct interaction and the beneficial effects of
      such interaction on the fertilizing ability of human spermatozoa. Anti-sFUT5
      antibody-treated spermatozoa had reduced binding to oviductal membrane proteins.
      It is consistent with the result that affinity-purified sFUT5 is bound to the
      epithelial lining of human oviduct and to the immortalized human oviductal
      epithelial cell line, OE-E6/E7. Pretreatment of spermatozoa with anti-sFUT5
      antibody and oviductal membrane proteins with sFUT5 suppressed the protective
      action of oviductal membrane proteins against ROS/cryopreservation-induced
      oxidative damage in spermatozoa. Asialofetuin, a reported sFUT5 substrate, can
      partly mimic the protective effect of oviductal epithelial cell membrane proteins
      on sperm motility, membrane and DNA integrity. The results enhance our
      understanding on the protective mechanism of oviduct on sperm functions. 

PMID- 25858481
TI  - Severe osteogenesis imperfecta caused by double glycine substitutions near the
      amino-terminal triple helical region in COL1A2.
AB  - Most cases of osteogenesis imperfecta (OI) are caused by heterozygous mutations
      in COL1A1 or COL1A2, the genes encoding the two type I procollagen alpha chains,
      proalpha1 (I) and proalpha2 (I). We report on a unique case of severe OI, a long
      term survivor of lethal type II OI, rather than progressively deforming type III,
      due to double substitutions of glycine residues in COL1A2 (p.Gly208Glu and
      p.Gly235Asp), located on the same allele. To the best of our knowledge, this is
      the first example of a patient with double COL1A2 glycine substitution mutations
      on the same allele. We show for the first time that double COL1A2 glycine
      substitution mutations located near the amino-terminal triple helical region,
      which individually are likely to result in mild OI, cause severe OI in
      combination.

PMID- 25858482
TI  - Maternal obesity alters immune cell frequencies and responses in umbilical cord
      blood samples.
AB  - BACKGROUND: Maternal obesity is one of the several key factors thought to
      modulate neonatal immune system development. Data from murine studies demonstrate
      worse outcomes in models of infection, autoimmunity, and allergic sensitization
      in offspring of obese dams. In humans, children born to obese mothers are at
      increased risk for asthma. These findings suggest a dysregulation of immune
      function in the children of obese mothers; however, the underlying mechanisms
      remain poorly understood. The aim of this study was to examine the relationship
      between maternal body weight and the human neonatal immune system. METHODS:
      Umbilical cord blood samples were collected from infants born to lean,
      overweight, and obese mothers. Frequency and function of major innate and
      adaptive immune cell populations were quantified using flow cytometry and
      multiplex analysis of circulating factors. RESULTS: Compared to babies born to
      lean mothers, babies of obese mothers had fewer eosinophils and CD4 T helper
      cells, reduced monocyte and dendritic cell responses to Toll-like receptor
      ligands, and increased plasma levels of IFN-alpha2 and IL-6 in cord blood.
      CONCLUSION: These results support the hypothesis that maternal obesity influences
      programming of the neonatal immune system, providing a potential link to
      increased incidence of chronic inflammatory diseases such as asthma and
      cardiovascular disease in the offspring.

PMID- 25858483
TI  - Bortezomib-based therapy combined with high cut-off hemodialysis is highly
      effective in newly diagnosed multiple myeloma patients with severe renal
      impairment.
AB  - Multiple myeloma (MM) is often associated with renal insufficiency (RI) which
      adversely influences the prognosis. Several studies demonstrated that bortezomib
      can improve both renal function and outcome. We prospectively evaluated 21 newly
      diagnosed MM patients with severe renal impairment secondary to tubular
      interstitial damage, most of them due to myeloma kidney, who were primarily
      treated with bortezomib-based therapy combined with high cut-off hemodialysis
      (HCOD). The median serum creatinine level at baseline was 6.44 mg dL(-1) and
      calculated median estimated glomerular filtration rate (eGFR), according to
      Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation,
      was 8 mL/min/1.73 m(2) . Serum free light chain (sFLC) median concentration was
      6,040 mg L(-1) . Post induction and best stringent complete response rates were
      19 and 38%, respectively. Responses were fast, occurring within a median of 1.4
      months. The combination of bortezomib and HCOD led to a prompt and remarkable
      (>90%) decrease in sFLC levels. Sixteen patients (76%) became dialysis
      independent within a median of 32 days. With a median follow up of 17.2 months,
      the 3-year PFS and OS were 76 and 67%, respectively. No early deaths were
      observed. This study demonstrates that incorporation of bortezomib into induction
      therapy combined with HCOD is a highly effective strategy in rescuing renal
      function and improving outcomes in patients with MM and RI.

PMID- 25858484
TI  - Detection and quantification of dental plaque based on laser-induced
      autofluorescence intensity ratio values.
AB  - The aim of this study was to evaluate the applicability of laser-induced
      autofluorescence (LIAF) spectroscopy to detect and quantify dental plaque. LIAF
      spectra were recorded in situ from dental plaque (0-3 grades of plaque index) in
      300 patients with 404 nm diode laser excitation. The fluorescence intensity ratio
      of the emission peaks was calculated from the LIAF spectral data following which
      their scatter plots were drawn and the area under the receiver operating
      characteristics were calculated. The LIAF spectrum of clinically invisible grade
      1 plaque showed a prominent emission peak at 510 nm with a satellite peak around
      630 nm in contrast to grade 0 that has a single peak around 500 nm. The
      fluorescence intensity ratio (F510/F630) has a decreasing trend with increase in
      plaque grade and the ratio values show statistically significant differences
      (p<0.01) between different grades. An overall sensitivity and specificity of 100%
      each was achieved for discrimination between grade-0 and grade-1 plaque. The
      clinical significance of this study is that the diagnostic algorithm developed
      based on fluorescence spectral intensity ratio (F510/F630) would be useful to
      precisely identify minute amounts of plaque without the need for disclosing
      solutions and to convince patients of the need for proper oral hygiene and
      homecare practices.

PMID- 25858485
TI  - Interaction between valence of empathy and familiarity: is it difficult to
      empathize with the positive events of a stranger?
AB  - BACKGROUND: Empathy in humans is thought to have evolved via social interactions
      caused by the formation of social groups. Considering the role of empathy within
      a social group, there might be a difference between emotional empathy for
      strangers and familiar others belonging to the same social group. In this study,
      we used the global field power (GFP) index to investigate empathic brain activity
      during observation of a cue indicating either a negative or positive image viewed
      by a stranger or close friend. METHODS: Sixteen healthy participants observed a
      partner performing an emotional gambling task displayed on a monitor. After the
      partner's choice-response, a frowning or smiling face symbol was simultaneously
      presented to the participant's monitor while a negative or positive emotional
      image was presented to the partner's monitor. All participants observed a control
      condition (CT) showing a computer trial, a stranger-observation condition (SO)
      showing the trial of a stranger, and a friend-observation condition (FO) to
      observe the trial of a close friend. During these observations, participants'
      event-related potentials (ERPs) were recorded to calculate GFP, and after the
      task, a subjective assessment of their feelings was measured. RESULTS: Positive
      emotion was significantly larger under the FO compared to the CT and the SO.
      Significantly larger negative emotion was found under the SO and FO compared to
      the CT. In response to a positive cue, significantly larger GFP during 300 to 600
      ms was observed under the FO compared to the CT and SO. In response to a negative
      cue, significantly larger GFP was observed under the FO and SO compared to the
      CT. A significantly larger GFP under the SO was found in response to only a
      negative cue. Topographic map analysis suggested that these differences were
      related to frontal-occipital dynamics. GFP was significantly correlated with
      empathic trait. CONCLUSION: These results revealed that familiarity with another
      person has different effects depending on the valence of empathy. Negative
      empathy, including the danger perception function, might easily occur even among
      strangers, whereas positive empathy related to nursing and supporting an inner
      group does not happen easily with strangers.

PMID- 25858486
TI  - 17-AAG post-treatment ameliorates memory impairment and hippocampal CA1 neuronal
      autophagic death induced by transient global cerebral ischemia.
AB  - Neuro-inflammation plays an important role in global cerebral ischemia (GCI). The
      72-kDa heat shock protein (Hsp70) has been reported to be involved in the
      inflammatory response of many central nervous system diseases. Preclinical
      findings implicate that 17-allylamino-demethoxygeldanamycin (17-AAG), an
      anticancer drug in clinical, provide neuroprotection actions in a rat model of
      traumatic brain injury, and the beneficial effects of 17-AAG were specifically
      due to up-regulation of Hsp70. However, no experiments have tested whether 17-AAG
      has beneficial or harmful effects in the setting of GCI. The present study was
      designed to determine the hypothesis that administration of 17-AAG could
      attenuate cerebral infarction and improve neuronal survival, thereby ameliorating
      memory impairment in a rat model of GCI. Furthermore, to test whether any
      neuroprotective effect of 17-AAG was associated with inflammatory response and
      neuronal autophagy, we examined the expression of multiplex inflammatory cytokine
      levels as well as autophagy-associate protein in hippocampal CA1 of rat brain.
      Our results showed that post-GCI administration of 17-AAG significantly protected
      rats against GCI induced brain injury, and 17-AAG is also an effective antagonist
      of the inflammatory response and thereby ameliorates hippocampal CA1 neuronal
      autophagic death. We therefore believe that the present study provides novel
      clues in understanding the mechanisms by which 17-AAG exerts its neuroprotective
      activity in GCI. All data reveal that 17-AAG might be a potential neuroprotective
      agent for ischemic stroke. 

PMID- 25858487
TI  - Aryl hydrocarbon receptor regulates CYP1B1 but not ABCB1 and ABCG2 in hCMEC/D3
      human cerebral microvascular endothelial cells after TCDD exposure.
AB  - The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor
      activated by a variety of widespread persistent environmental pollutants such as
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). It can transactivate the expression
      of several target genes. Recently AhR transcripts were detected in isolated human
      brain microvessels and in the hCMEC/D3 human cerebral microvascular endothelial
      cell line, an in vitro model of the human cerebral endothelium. To date AhR
      implication in the co-regulation of ABCB1, ABCG2 and CYP1B1 at human cerebral
      endothelium has not been addressed. Here we investigated whether AhR could co
      regulate ABCB1, ABCG2 and CYP1B1 expressions in the hCMEC/D3 cell line. Exposure
      to TCDD induced a concentration-dependent increase in CYP1B1 expression. We
      demonstrated AhR involvement in the TCDD-mediated increase in CYP1B1 expression
      by using small interfering RNA against AhR. Western blotting analysis also
      revealed an increase in CYP1B1 protein expression following TCDD exposure in
      hCMEC/D3. Regarding ABCB1 and ABCG2, exposure to TCDD had no effect on their
      protein expressions and functional activities. In conclusion our data indicated a
      differential modulation of CYP1B1 and ABCB1/ABCG2 expressions in hCMEC/D3 cells
      following TCDD exposure. 

PMID- 25858488
TI  - The linguistic context effects on the processing of body-object interaction
      words: An ERP study on second language learners.
AB  - Embodied theories of cognition argue that the processing of both concrete and
      abstract concepts requires the activation of sensorimotor systems. The present
      study examined the time course for embedding a sensorimotor context in order to
      elicit sensitivity to the sensorimotor consequences of understanding body-object
      interaction (BOI) words. In the study, Event-Related Potentials (ERPs) were
      recorded while subjects performed a sentence acceptability task. Target BOI words
      were preceded by rich or poor sensorimotor sentential contexts. The behavioural
      results replicated previous findings in that high BOI words received a response
      faster than low BOI words. In addition to this, however, there was a context
      effect in the sensorimotor region as well as a BOI effect in the parietal region
      (involved in object representation). The results indicate that the sentential
      sensorimotor context contributes to the subsequent BOI processing and that action
      and perception-related language leads to the activation of the same brain areas,
      which is consistent with the embodiment theory. 

PMID- 25858489
TI  - Preparation and in vitro antioxidant activities of 6-amino-6-deoxychitosan and
      its sulfonated derivatives.
AB  - The 6-amino-6-deoxychitosan (NC) and their 2, 6-di-N-sulfonated derivatives were
      prepared via N-phthaloylation, tosylation, azidation, hydrazinolysis, reduction
      of azide groups and N-sulfonation, and their structures were systematically
      characterized by FT-IR, 2D HSQC NMR, XRD, gel permeation chromatography (GPC),
      and elemental analysis. The 6-amino-6-deoxychitosan showed effect in three
      selected antioxidant essays, including reducing power, superoxide anion radical
      scavenging ability, and hydroxyl radical scavenging effect. But the factors
      affecting each activity were different. The reducing power and the superoxide
      anion radical scavenging ability of NC were strong and closely related to the
      amino groups in the molecular chains. Both introducing N-sulfonated groups into
      NC and the concentration reduction of NC and its sulfonated derivatives decreased
      these activities. For the superoxide anion radical, the molecular charge property
      was also a significant influence factor. For the hydroxyl radical, NC only showed
      weak scavenging activity in a special inverse concentration-dependent manner.
      However, the incorporation of N-sulfonated groups significantly improved the
      scavenging activity, and the more N-sulfonated groups, the higher the
      concentrations, the stronger the activity was. The results could be due to the
      different conformations of NC and its sulfonated derivatives in aqueous solution.

PMID- 25858490
TI  - Stroke survivors' and family members' perspectives of multimodal lifestyle
      interventions for secondary prevention of stroke and transient ischemic attack: a
      qualitative review and meta-aggregation.
AB  - PURPOSE: The incidence of stroke is of global concern, and the rates of
      recurrence are high. Many risk factors are related to lifestyle behaviours and,
      as such, are amenable to change. Implementation of effective secondary prevention
      interventions is essential; however, little is known about influences on
      participation and adherence. This review and meta-aggregation aimed to improve
      understanding of stroke survivor and family member perspectives of secondary
      prevention interventions. METHODS: We searched 11 databases, e.g. Medline and
      PsycINFO. We included qualitative studies that focused on adult stroke survivors
      and family members who had participated in a multimodal stroke secondary
      prevention intervention. Critical appraisal and data extraction were performed
      independently by two reviewers. A meta-aggregation of qualitative findings was
      conducted. RESULTS: Five papers were included. One hundred and three findings
      were extracted and grouped into 14 categories from which three synthesised
      findings emerged: feeling supported, acquiring knowledge and gaining confidence.
      CONCLUSIONS: The findings highlight the perceived benefits of participation in
      secondary prevention group interventions from the perspective of stroke survivors
      and family members, i.e. feeling supported, by others with shared understanding
      and by knowledgeable health professionals, acquiring new knowledge and gaining
      confidence. These findings may be used to inform development of patient-centred
      interventions and thereby assist in improving health outcomes. IMPLICATIONS FOR
      REHABILITATION: Health professionals should consider implementing group-based
      secondary prevention interventions. The content of group-based secondary
      prevention interventions should be person-centred, i.e. meaningful and relevant
      to the individual. Stroke survivors and family members are more likely to comply
      with advice and information provided by expert and experienced health
      professionals.

PMID- 25858491
TI  - Role of calcium ions in the positive interaction between TRPA1 and TRPV1 channels
      in bronchopulmonary sensory neurons.
AB  - Both transient receptor potential ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1)
      receptors are abundantly expressed in bronchopulmonary C-fiber sensory nerves and
      can be activated by a number of endogenous inflammatory mediators. A recent study
      has reported a synergistic effect of simultaneous TRPA1 and TRPV1 activations in
      vagal pulmonary C-fiber afferents in anesthetized rats, but its underlying
      mechanism was not known. This study aimed to characterize a possible interaction
      between these two TRP channels and to investigate the potential role of Ca(2+) as
      a mediator of this interaction in isolated rat vagal pulmonary sensory neurons.
      Using the perforated patch-clamp recording technique, our study demonstrated a
      distinct positive interaction occurring abruptly between TRPA1 and TRPV1 when
      they were activated simultaneously by their respective agonists, capsaicin (Cap)
      and allyl isothiocyanate (AITC), at near-threshold concentrations in these
      neurons. AITC at this low concentration evoked only minimal or undetectable
      responses, but it markedly amplified the Cap-evoked current in the same neurons.
      This potentiating effect was eliminated when either AITC or Cap was replaced by
      non-TRPA1 and non-TRPV1 chemical activators of these neurons, demonstrating the
      selectivity of the interaction between these two TRP channels. Furthermore, when
      Ca(2+) was removed from the extracellular solution, the synergistic effect of Cap
      and AITC on pulmonary sensory neurons was completely abrogated, clearly
      indicating a critical role of Ca(2+) in mediating the action. These results
      suggest that this TRPA1-TRPV1 interaction may play a part in regulating the
      sensitivity of pulmonary sensory neurons during airway inflammatory reaction. 

PMID- 25858493
TI  - Ultrasound-induced modulation of cardiac rhythm in neonatal rat ventricular
      cardiomyocytes.
AB  - Isolated neonatal rat ventricular cardiomyocytes were used to study the influence
      of ultrasound on the chronotropic response in a tissue culture model. The beat
      frequency of the cells, varying from 40 to 90 beats/min, was measured based upon
      the translocation of the nuclear membrane captured by a high-speed camera.
      Ultrasound pulses (frequency = 2.5 MHz) were delivered at 300-ms intervals [3.33
      Hz pulse repetition frequency (PRF)], in turn corresponding to 200 pulses/min.
      The intensity of acoustic energy and pulse duration were made variable, 0.02-0.87
      W/cm(2) and 1-5 ms, respectively. In 57 of 99 trials, there was a noted average
      increase in beat frequency of 25% with 8-s exposures to ultrasonic pulses.
      Applied ultrasound energy with a spatial peak time average acoustic intensity
      (Ispta) of 0.02 W/cm(2) and pulse duration of 1 ms effectively increased the
      contraction rate of cardiomyocytes (P < 0.05). Of the acoustic power tested, the
      lowest level of acoustic intensity and shortest pulse duration proved most
      effective at increasing the electrophysiological responsiveness and beat
      frequency of cardiomyocytes. Determining the optimal conditions for delivery of
      ultrasound will be essential to developing new models for understanding
      mechanoelectrical coupling (MEC) and understanding novel nonelectrical pacing
      modalities for clinical applications. 

PMID- 25858492
TI  - Selective optogenetic stimulation of the retrotrapezoid nucleus in sleeping rats
      activates breathing without changing blood pressure or causing arousal or sighs.
AB  - Combined optogenetic activation of the retrotrapezoid nucleus (RTN; a CO2/proton
      activated brainstem nucleus) with nearby catecholaminergic neurons (C1 and A5),
      or selective C1 neuron stimulation, increases blood pressure (BP) and breathing,
      causes arousal from non-rapid eye movement (non-REM) sleep, and triggers sighs.
      Here we wished to determine which of these physiological responses are elicited
      when RTN neurons are selectively activated. The left rostral RTN and nearby A5
      neurons were transduced with channelrhodopsin-2 (ChR2(+)) using a lentiviral
      vector. Very few C1 cells were transduced. BP, breathing, EEG, and neck EMG were
      monitored. During non-REM sleep, photostimulation of ChR2(+) neurons (20s, 2-20
      Hz) instantly increased Ve without changing BP (13 rats). Ve and BP were
      unaffected by light in nine control (ChR2(-)) rats. Photostimulation produced no
      sighs and caused arousal (EEG desynchronization) more frequently in ChR2(+) than
      ChR2(-) rats (62 +/- 5% of trials vs. 25 +/- 2%; P < 0.0001). Six ChR2(+) rats
      then received spinal injections of a saporin-based toxin that spared RTN neurons
      but destroyed surrounding catecholaminergic neurons. Photostimulation of the
      ChR2(+) neurons produced the same ventilatory stimulation before and after
      lesion, but arousal was no longer elicited. Overall (all ChR2(+) rats combined),
      DeltaVe correlated with the number of ChR2(+) RTN neurons whereas arousal
      probability correlated with the number of ChR2(+) catecholaminergic neurons. In
      conclusion, RTN neurons activate breathing powerfully and, unlike the C1 cells,
      have minimal effects on BP and have a weak arousal capability at best. A5 neuron
      stimulation produces little effect on breathing and BP but does appear to
      facilitate arousal. 

PMID- 25858494
TI  - Inorganic nitrate supplementation improves muscle oxygenation, O2 uptake
      kinetics, and exercise tolerance at high but not low pedal rates.
AB  - We tested the hypothesis that inorganic nitrate (NO3 (-)) supplementation would
      improve muscle oxygenation, pulmonary oxygen uptake (Vo2) kinetics, and exercise
      tolerance (Tlim) to a greater extent when cycling at high compared with low pedal
      rates. In a randomized, placebo-controlled cross-over study, seven subjects (mean
      +/- SD, age 21 +/- 2 yr, body mass 86 +/- 10 kg) completed severe-intensity step
      cycle tests at pedal cadences of 35 rpm and 115 rpm during separate nine-day
      supplementation periods with NO3 (-)-rich beetroot juice (BR) (providing 8.4 mmol
      NO3 (-)/day) and placebo (PLA). Compared with PLA, plasma nitrite concentration
      increased 178% with BR (P < 0.01). There were no significant differences in
      muscle oxyhemoglobin concentration ([O2Hb]), phase II Vo2 kinetics, or Tlim
      between BR and PLA when cycling at 35 rpm (P > 0.05). However, when cycling at
      115 rpm, muscle [O2Hb] was higher at baseline and throughout exercise, phase II
      Vo2 kinetics was faster (47 +/- 16 s vs. 61 +/- 25 s; P < 0.05), and Tlim was
      greater (362 +/- 137 s vs. 297 +/- 79 s; P < 0.05) with BR compared with PLA.
      These results suggest that short-term BR supplementation can increase muscle
      oxygenation, expedite the adjustment of oxidative metabolism, and enhance
      exercise tolerance when cycling at a high, but not a low, pedal cadence in
      healthy recreationally active subjects. These findings support recent
      observations that NO3 (-) supplementation may be particularly effective at
      improving physiological and functional responses in type II muscle fibers.

PMID- 25858495
TI  - Late-onset pyoderma gangrenosum following surgical operation in a patient with
      malignant melanoma.

PMID- 25858496
TI  - Y chromosome haplogroup D2a1 is significantly associated with high levels of
      luteinizing hormone in Japanese men.
AB  - The association between the Y chromosome haplogroup D2 and risk of azoospermia
      and low sperm motility has been previously studied, and it was indicated that
      haplogroups DE (YAP lineage) are associated with prostate cancer risk in Japanese
      males. Our assumption had been that Y chromosome haplogroups may be associated
      with sex hormone levels, because sex hormones have been deemed responsible for
      spermatogenesis and carcinogenesis. In this study, we assessed the association
      between Y chromosome haplogroups and sex hormone levels, including those of
      testosterone, sex hormone-binding globulin (SHBG), follicle-stimulating hormone
      (FSH), luteinizing hormone (LH), inhibin-B, and calculated free testosterone
      (cFT), in 901 young men from the general Japanese population (cohort 1) and 786
      Japanese men of proven fertility (cohort 2). We found that the haplogroup D2a1
      was significantly associated with high LH levels in a combined analysis involving
      two cohorts (beta = 0.068, SE = 0.025, p = 0.0075), following correction for
      multiple testing. To date, this result is the first evidence that implicates Y
      chromosome haplogroups in an association with sex hormone levels.

PMID- 25858497
TI  - A randomized, placebo-controlled phase III trial of masitinib plus gemcitabine in
      the treatment of advanced pancreatic cancer.
AB  - BACKGROUND: Masitinib is a selective oral tyrosine-kinase inhibitor. The efficacy
      and safety of masitinib combined with gemcitabine was compared against single
      agent gemcitabine in patients with advanced pancreatic ductal adenocarcinoma
      (PDAC). PATIENTS AND METHODS: Patients with inoperable, chemotherapy-naive, PDAC
      were randomized (1 : 1) to receive gemcitabine (1000 mg/m(2)) in combination with
      either masitinib (9 mg/kg/day) or a placebo. The primary endpoint was overall
      survival (OS) in the modified intent-to-treat population. Secondary OS analyses
      aimed to characterize subgroups with poor survival while receiving single-agent
      gemcitabine with subsequent evaluation of masitinib therapeutic benefit. These
      prospectively declared subgroups were based on pharmacogenomic data or a baseline
      characteristic. RESULTS: Three hundred and fifty-three patients were randomly
      assigned to receive either masitinib plus gemcitabine (N = 175) or placebo plus
      gemcitabine (N = 178). Median OS was similar between treatment-arms for the
      overall population, at respectively, 7.7 and 7.1 months, with a hazard ratio (HR)
      of 0.89 (95% CI [0.70; 1.13]. Secondary analyses identified two subgroups having
      a significantly poor survival rate when receiving single-agent gemcitabine; one
      defined by an overexpression of acyl-CoA oxidase-1 (ACOX1) in blood, and another
      via a baseline pain intensity threshold (VAS > 20 mm). These subgroups represent
      a critical unmet medical need as evidenced from median OS of 5.5 months in
      patients receiving single-agent gemcitabine, and comprise an estimated 63% of
      patients. A significant treatment effect was observed in these subgroups for
      masitinib with median OS of 11.7 months in the 'ACOX1' subgroup [HR = 0.23 (0.10;
      0.51), P = 0.001], and 8.0 months in the 'pain' subgroup [HR = 0.62 (0.43; 0.89),
      P = 0.012]. Despite an increased toxicity of the combination as compared with
      single-agent gemcitabine, side-effects remained manageable. CONCLUSIONS: The
      present data warrant initiation of a confirmatory study that may support the use
      of masitinib plus gemcitabine for treatment of PDAC patients with overexpression
      of ACOX1 or baseline pain (VAS > 20mm). Masitinib's effect in these subgroups is
      also supported by biological plausibility and evidence of internal clinical
      validation. TRIAL REGISTRATION: ClinicalTrials.gov:NCT00789633.

PMID- 25858498
TI  - Doxorubicin plus the IGF-1R antibody cixutumumab in soft tissue sarcoma: a phase
      I study using the TITE-CRM model.
AB  - BACKGROUND: Insulin-like growth factor receptor (IGF-1R) has been studied as an
      oncologic target in soft tissue sarcoma (STS), but its role in sarcoma biology is
      unclear. Anti-IGF-1R antibody cixutumumab demonstrated acceptable toxicity but
      limited activity as a single agent in STS. We carried out a dose-escalation study
      of cixutumumab with doxorubicin to evaluate safety and dosing of the combination.
      PATIENTS AND METHODS: Eligible patients with advanced STS were treated with
      cixutumumab intravenously on days 1/8/15 at one of three dose levels (A: 1 mg/kg,
      B: 3 mg/kg, C: 6 mg/kg) with doxorubicin at 75 mg/m(2) as a 48 h infusion on day
      1 of a 21 day cycle. After six cycles of the combination, patients could receive
      cixutumumab alone. The Time-to-Event Continual Reassessment Method was used to
      estimate the probability of dose-limiting toxicity (DLT) and to assign patients
      to the dose with an estimated probability of DLT<=20%. RESULTS: Between September
      2008 and January 2012, 30 patients with advanced STS received a median of six
      cycles of therapy (range <1-22). Two DLTs were observed, grade 3 mucositis (dose
      level B) and grade 4 hyperglycemia (dose level C). Grade 2 and 3 reduced left
      ventricular ejection fraction was seen in three and two patients, respectively.
      Five partial responses were observed, and estimated progression-free survival was
      5.3 months (95% confidence interval 3.0-6.3) in 26 response-assessable patients.
      Immunohistochemical staining of 11 available tumor samples for IGF-1R and phospho
      IGF-1R was not significantly different among responders and non-responders, and
      serum analysis of select single-nucleotide polymorphisms did not predict for
      cardiotoxicity. CONCLUSION: The maximum tolerated dose was doxorubicin 75 mg/m(2)
      on day 1 and cixitumumab 6 mg/kg on days 1/8/15 of a 21 day cycle. Cardiac
      toxicity was observed and should be monitored in subsequent studies, which should
      be considered in STS only if a predictive biomarker of benefit to anti-IGF-1R
      therapy is identified. TRIAL REGISTRATION: ClinicalTrials.gov:NCT00789633.

PMID- 25858499
TI  - (111)In-octreotide SPECT-CT in head and neck paragangliomas.
AB  - Head and neck paragangliomas are rare neuroendocrine tumors expressing
      somatostatin receptors on their cell surface, particularly subtype 2. Due to this
      distinctive feature, images can be obtained in Nuclear Medicine using synthetic
      analogues of somatostatin, mainly octreotide, which allow selective display by
      planar scintigraphy, SPECT-CT or PET-CT imaging after radiolabeling with (111)In
      or (68)Ga. Three cases have been selected and presented from a series of patients
      that illustrate the utility of SPECT-CT studies with (111)In-octreotide in the
      diagnosis and monitoring of this type of tumor. These are characterization at
      initial diagnosis, staging, and detection of local recurrence or metastasis, with
      added value with respect to anatomical images (nuclear magnetic resonance,
      computed axial tomography, angiography), for example in the differentiation
      between functional tissue or scar in patients who had previously undergone
      surgery. 

PMID- 25858501
TI  - Reflecting on 'Equity in health care: the Irish perspective'.

PMID- 25858500
TI  - Immunoglobulin G4-related disease (IgG4-RD) in the orbit: mucosa-associated
      lymphoid tissue (MALT)-type lymphomas.
AB  - BACKGROUND: MALT lymphomas were classified for differential diagnostics of IgG4
      dependent disease due to their exceptional predilection to intraorbital
      localization. Therefore, the goal of our studies was large retrospective analysis
      of patients diagnosed with MALT lymphomas within the orbital tissues, since no
      such studies have been conducted in Poland. MATERIAL/METHODS: The starting study
      population consisted of 167 patients with isolated infiltrative tumor diseases
      within the orbital region treated at the Department of Otolaryngology, Head and
      Neck Surgery of the Medical College Jagiellonian University in Cracow. The
      immunohistochemical assays using anti-IgG, anti-IgG4 and anti-CD138 antibodies
      were used to estimate the IgG4+/CD138+ and IgG4+/IgG+ ratios. RESULTS: Of all the
      studied and analyzed patients, a final group of 19 patients with orbital MALT
      lymphomas was selected to undergo diagnostic examinations for IgG4-related
      disease. Detailed analysis and diagnostic screening for IgG4-related disease was
      performed and results meeting the criteria of IgG4-dependent disease were
      obtained in 10 out of 19 patients with the diagnosis of MALT tumor established on
      the basis of immunohistochemical assays. CONCLUSIONS: MALT lymphomas are the most
      common of all lymphomas occurring within orbital tissues. In this study, results
      consistent with the criteria of IgG4-related disease were obtained in
      approximately 50% patients with immunohistochemical diagnosis of orbital MALT
      lymphoma.

PMID- 25858502
TI  - Matrix Metalloproteinase Expression in Contusional Traumatic Brain Injury: A
      Paired Microdialysis Study.
AB  - Matrix metalloproteinases (MMPs) are extracellular enzymes that have been
      implicated in the pathophysiology of blood-brain barrier (BBB) breakdown,
      contusion expansion, and vasogenic edema after traumatic brain injury (TBI).
      Specifically, in focal injury models, increased MMP-9 expression has been
      observed in pericontusional brain, and MMP-9 inhibitors reduce brain swelling and
      final lesion volume. The aim of this study was to examine whether there is a
      similarly localized increase of MMP concentrations in patients with contusional
      TBI. Paired microdialysis catheters were inserted into 12 patients with
      contusional TBI (with or without associated mass lesion) targeting
      pericontusional and radiologically normal brain defined on admission computed
      tomography scan. Microdialysate was pooled every 8 h and analyzed for MMP-1, -2, 
      7, -9, and -10 using a multiplex immunoassay. Concentrations of MMP-1, -2, and 
      10 were similar at both monitoring sites and did not show discernible temporal
      trends. Overall, there was a gradual increase in MMP-7 concentrations in both
      normal and injured brain over the monitoring period, although this was not
      consistent in every patient. MMP-9 concentrations were elevated in
      pericontusional, compared to normal, brain, with the maximal difference at the
      earliest monitoring times (i.e., <24 h postinjury). Repeated-measures analysis of
      variance showed that MMP-9 concentrations were significantly higher in
      pericontusional brain (p=0.03) and within the first 72 h of injury, compared with
      later in the monitoring period (p=0.04). No significant differences were found
      for the other MMPs assayed. MMP-9 concentrations are increased in pericontusional
      brain early post-TBI and may represent a potential therapeutic target to reduce
      hemorrhagic progression and vasogenic edema.

PMID- 25858504
TI  - Geographical and geological origin of natural graphite heavily influence the
      electrical and electrochemical properties of chemically modified graphenes.
AB  - Natural graphite is an important precursor for the production of chemically
      modified graphenes in bulk quantities for electrochemical applications. These
      natural graphites have varying fundamental properties due to the different
      geological processes and environments at their points of origin, which are
      expected to affect their chemical reactivity and hence the properties of the
      derived graphene materials. Four different natural graphites with known
      geographical and geological origins were exposed to a modified Hummers oxidation
      method and the resulting graphite oxides were studied. The graphite oxides were
      shown to have different extents of oxidation and types of oxygen groups, which
      directly influenced their electrochemical properties. These differences were
      propagated further in the subsequent chemical reduction of the graphite oxides,
      and the reduced graphene oxides exhibited significantly different reduction
      efficiencies and electrical conductivities. These findings show that the choice
      of natural graphite of known origin is important to synthesize chemically
      modified graphenes with a desired set of properties. 

PMID- 25858503
TI  - Pharmacologically blocking p53-dependent apoptosis protects intestinal stem cells
      and mice from radiation.
AB  - Exposure to high levels of ionizing radiation (IR) leads to debilitating and dose
      limiting gastrointestinal (GI) toxicity. Using three-dimensional mouse crypt
      culture, we demonstrated that p53 target PUMA mediates radiation-induced
      apoptosis via a cell-intrinsic mechanism, and identified the GSK-3 inhibitor
      CHIR99021 as a potent radioprotector. CHIR99021 treatment improved Lgr5+ cell
      survival and crypt regeneration after radiation in culture and mice. CHIR99021
      treatment specifically blocked apoptosis and PUMA induction and K120 acetylation
      of p53 mediated by acetyl-transferase Tip60, while it had no effect on p53
      stabilization, phosphorylation or p21 induction. CHIR99021 also protected human
      intestinal cultures from radiation by PUMA but not p21 suppression. These results
      demonstrate that p53 posttranslational modifications play a key role in the
      pathological and apoptotic response of the intestinal stem cells to radiation and
      can be targeted pharmacologically. 

PMID- 25858506
TI  - Corrigendum.

PMID- 25858505
TI  - Biochemistry-Enabled 3D Foams for Ultrafast Battery Cathodes.
AB  - Metal vanadium phosphates (MVP), particularly Li3V2(PO4)3 (LVP) and Na3V2(PO4)3
      (NVP), are regarded as the next-generation cathode materials in lithium/sodium
      ion batteries. These materials possess desirable properties such as high
      stability, theoretical capacity, and operating voltages. Yet, low
      electrical/ionic conductivities of LVP and NVP have limited their applications in
      demanding devices such as electric vehicles. In this work, a novel synthesis
      route for the preparation of LVP/NVP micro/mesoporous 3D foams via assembly of
      elastin-like polypeptides is demonstrated. The as-synthesized MVP 3D foams
      consist of microporous networks of mesoporous nanofibers, where the surfaces of
      individual fibers are covered with MVP nanocrystallites. TEM images further
      reveal that LVP/NVP nanoparticles are about 100-200 nm in diameter, with each
      particle enveloped by a 5 nm thick carbon shell. The MVP 3D foams prepared in
      this work exhibit ultrafast rate capabilities (79 mA h g(-1) at 100C and 66 mA h
      g(-1) at 200C for LVP 3D foams; 73 mA h g(-1) at 100C and 51 mA h g(-1) at 200C
      for NVP 3D foams) and excellent cycle performance (almost 100% performance
      retention after 1000 cycles at 100C); their properties are far superior compared
      to current state-of-the-art active materials. 

PMID- 25858507
TI  - Taraxacum officinale and related species-An ethnopharmacological review and its
      potential as a commercial medicinal plant.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Dandelion (Taraxacum spec) is a wild plant that
      has been used for centuries as a traditional medicine in the relief and treatment
      of several diseases. This use is due to the presence of sesquiterpenes, saponins,
      phenolic compounds, flavonoids, and sugars, among others, found in the organs of
      the plant. AIM OF THE STUDY: The aim of this work is to provide a current review
      of developments and trends in research on the Taraxacum genus, with a focus on
      traditional uses and pharmacological properties. This should shed light on the
      potential of this plant as an attractive commercial herbal medicine. MATERIALS
      AND METHODS: Documents were collected, analyzed, and classified for information
      regarding medical, agronomic, genetic, and biological aspects of the Taraxacum
      species. This process was based on a thorough search of documents indexed by
      scientific search engines. RESULTS: Two important periods of research on
      Taraxacum have been identified: the first, between 1930 and 1950; and the second,
      from 1990 to today. During the former, agricultural and genetics research on this
      plant were, due to the shortage of natural rubber, the focus. In contrast, the
      main drive in Taraxacum research is now the recovery of bioactives and/or
      applications in medicine. Pharmacology is the main area in which these plants
      have been tested, thanks in part to its widely known traditional uses; however,
      there is less than enthusiastic interest in further human clinical trials. In
      other areas, Taraxacum sports an enormous list of compounds of industrial
      interest; and while it is true that only a small amount of these compounds is
      immediately available in Taraxacum organs and makes it relatively commercially
      unattractive, only scarce efforts have been made to improve yields. Compounding
      this issue, most studies of its growth and cultivation have been focused mainly
      on controlling it as a weed detrimental to certain industrial crops. To wit, in
      spite of all the research carried out, less than 1% of all the species identified
      so far (>2500) have been studied (including Taraxacum officinale, Taraxacum
      coreanum, Taraxacum mongolicum and Taraxacum platycarpum). This is a indication
      of the little knowledge that we have about this genus so far. Biotechnology
      (involving genetics, agriculture, and biology) is the most powerful means by
      which to take advantage of all the medicinal potential of Taraxacum. Great
      strides have been made in identifying metabolic pathways for synthesizing
      terpenes, one of the most important compound families in clinical applications.
      In order to improve yield and performance of the plant in the field, greenhouse
      cultivation is another aspect taken into account, deriving an increase in
      recovery of bioactives from Taraxacum organs. Even while considering that only a
      few species have been studied, their different biochemical and cultivation
      profiles indicate huge potential for qualitative improvements in composition
      through genetic engineering, thus directly impacting pharmacological properties.
      CONCLUSIONS: Taraxacum is has been traditionally considered a natural remedy,
      well-inserted into popular knowledge, but with low commercial applicability. Only
      once the recovery of pure and highly reactive compounds can be pursued at (a
      qualitatively and quantitatively attractive) economical scale, human clinical
      trials would be of interest in order to prove their efficacy and safety,
      positioning Taraxacum as an important commercial source of natural drugs.

PMID- 25858508
TI  - Mechanism-based inhibition of Alantolactone on human cytochrome P450 3A4 in vitro
      and activity of hepatic cytochrome P450 in mice.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Alantolactone (AL), one of the main active
      ingredients in Inula helenium L., has been included in various prescriptions of
      traditional Chinese medicine. The effects of AL on cytochrome P450 (CYP450) were
      still unclear. This study evaluated the inhibitory effect of AL on cytochrome
      P450s in vitro and in vivo. MATERIALS AND METHODS: The inhibitory effects of AL
      on the CYPs activity were evaluated in human liver microsomes (HLMs) and
      recombinant cDNA-expressed enzymes incubation system, and then determined by LC
      MS/MS based CYPs probe substrate assay. C57BL/6 mice were treated AL orally (0,
      25, 50, 100 mg/kg) for 15 days. The inhibitory effects of AL on major Cyps in
      mice were examined at both the mRNA and enzyme activity levels. RESULTS: AL
      showed a potent inhibitory effect on CYP3A4 activity with IC50 values of 3.599
      (HLMs) and 3.90 (recombinant CYP3A4) MUM, respectively. AL strongly decreased
      CYP3A4 activity in a dose-dependent but not time-dependent way in HLMs. Results
      from typical Lineweaver-Burk plots showed that AL could inhibit CYP3A4 activity
      noncompetitively, with a Ki value of 1.09 MUM in HLMs. Moreover, activity of
      CYP2C19 could also be inhibited by AL with IC50 of 36.82 MUM. Other CYP450
      isoforms were not markedly affected by AL. The inhibition was also validated by
      in vivo study of mice. AL significantly decreased mRNA expression of Cyp2c and 3a
      family. CONCLUSION: The study indicates that herb-drug interaction should be paid
      more attention between AL and drugs metabolized by CYP3A4.

PMID- 25858509
TI  - Polyphenols rich fraction of Dicranopteris linearis promotes fibroblast cell
      migration and proliferation in vitro.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Dicranopteris linearis is a fern used
      traditionally for the treatment of skin afflictions such as external wounds,
      boils and ulcers. However, there are no scientific studies to date to demonstrate
      its ability to induce wound recovery. The objective of the present study was to
      explore the wound healing properties of an active fraction of D. linearis through
      several in vitro assays and to determine its chemical profile. MATERIALS AND
      METHODS: The antioxidant activities were evaluated by DPPH and FRAP assays. The
      ability of the active fraction to induce fibroblast cell proliferation in serum
      deprived medium or under the challenge of exogenous hydrogen peroxide was
      evaluated by MTT assay. Cell migration was investigated using the scratch-wound
      assay. Chemical constituents of the active fraction were isolated and their
      structures were determined by NMR and MS spectroscopic techniques. Chemical
      profiling was carried out by the HPLC-UV method. RESULTS: The fifth subfraction
      of the methanol extract of D. linearis (sF5) showed prominent antioxidant
      activities. It was non-cytotoxic at the concentration tested and was able to
      induce cell proliferation of selected fibroblast cells under serum deprived
      conditions. In addition, sF5 was found to enhance cell migration and promote
      cellular repair following oxidative damage caused by hydrogen peroxide through a
      mechanism which was independent of its hydroxyl radical scavenging capability.
      Six phenolic glycosides were identified in sF5 where three were known, two were
      new and one phenolic glycoside first time reported from the plant. CONCLUSION:
      The active fraction of D. linearis which was rich in polyphenolic substances
      exhibited substantial antioxidant activities, induced cellular repair and
      contributed positively to fibroblasts proliferation and migration in vitro.
      Hence, it may have potential application in inducing wound recovery and supports
      its ethnopharmacological use for treating skin problems.

PMID- 25858510
TI  - O-prenylated flavonoid, an antidiabetes constituent in Melicope lunu-ankenda.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Melicope lunu-ankenda leaves are used to treat
      diabetes in folklore medicinal practices in India and Malaysia. Here we report
      the isolation of an O-prenylated flavonoid (3,5,4'-trihydroxy-8,3'-dimethoxy-7-(3
      methylbut-2-enoxy)flavone; OPF) from the leaves of M. lunu-ankenda and its
      antidiabetes activity against type-2 diabetes mellitus (T2DM). MATERIALS AND
      METHODS: OPF was isolated from M. lunu-ankenda leaves by extraction and repeated
      column chromatography and its structure was elucidated by IR, UV-vis, 1D-, 2D-NMR
      and mass spectral analyses. Blood glucose lowering activity of OPF was tested in
      normal rats by oral glucose tolerance test and its efficacy was tested in STZ
      induced type-2 diabetic rats. SGOT, SGPT, ALP, serum urea, total triglycerides,
      total cholesterol and reduction in HDLC, protein and serum insulin levels in
      normal rats and STZ-induced type-2 diabetic rats were measured. Acute toxicity of
      OPF was tested at 500 mg/kg dose. Mechanism of antidiabetes action of OPF was
      elucidated by insulin release from RIN 5F cells. RESULTS: OPF isolated from M.
      lunu-ankenda showed significant blood glucose lowering activity in oral glucose
      tolerance test on overnight fasted, glucose loaded normal rats and the optimum
      activity was observed at a dose of 10mg/kg body weight. In neonatal
      streptozotocin (STZ) induced diabetic rats, the OPF treatment for 20 days
      significantly ameliorated the derailed blood glucose levels, liver glycogen and
      serum biological parameters including insulin to normal levels. OPF on acute
      toxicity evaluation did not show any conspicuous toxic symptoms even at a higher
      dose of 500 mg/kg body weight in mice. On evaluating the mechanism of
      antidiabetes action, it was observed that, OPF induced insulin release from
      cultured RIN 5F cells in vitro from which it was evident that the OPF acts on
      pancreatic beta-cells for insulin release thereby correcting the derailed blood
      glucose levels, serum biochemical parameters and ameliorate various diabetic
      complications in STZ-induced diabetic rats. CONCLUSIONS: This study shows the
      potent antidiabetes activity of OPF and describes its mechanism of action. OPF is
      a promising candidate for the development of new generation anti-DM drugs.
      Isolation of the O-prenylated flavonoid justifies the use of M. lunu-ankenda for
      diabetic treatments in folklore practices.

PMID- 25858511
TI  - Antitumor immunostimulatory activity of polysaccharides from Salvia chinensis
      Benth.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Salvia chinensis Benth (S. chinensis) is a
      traditional herb applied in the treatment of hepatocellular carcinoma (HCC).
      Polysaccharides abundantly exist in this plant. However, it remains poorly
      understood if polysaccharides from S. chinensis (PSSC) contribute to its anti-HCC
      activity. MATERIALS AND METHODS: The in vivo anti-HCC activity of PSSC was
      evaluated in Kunming mice bearing H22 ascitic hepatoma cells. An array of
      physiological indexes was measured to evaluate toxicological effects on host
      animals. Subgroups of immune cells were purified by a magnetic-activated cell
      sorting system and analyzed by flow cytometry. Reverse transcription real-time
      PCR and immunoblotting were recruited to determine the effects of PSSC on the
      cellular signaling of different subgroup of immune cells. RESULTS: PSSC
      suppressed in vivo proliferation of H22 cells with undetectable toxic effects on
      tumor-bearing mice. PSSC alleviated tumor transplantation-induced CD4+ T cell
      apoptosis and dysregulation of serum cytokine profiles, which elevated cytotoxic
      activities of natural killer and CD8+ T cells. PSSC reduced serum levels of
      prostaglandin E2 (PGE2). Injection of exogenous PGE2 completely abrogated the
      antitumor immunostimulatory activity of PSSC. Cyclic adenosine monophosphate
      (cAMP) is the second messager of PGE2. In CD4+ T cells, PSSC substantially
      declined intracellular cAMP. This event elevated protein levels of JAK3,
      enhancing STAT5 phosphorylation and STAT5-dependent expression of anti-apoptotic
      genes. Cyclooxygenase-2 is the key enzyme mediating biosynthesis of PGE2. PSSC
      suppressed the transcription and translation of cyclooxygenase-2 in tumor
      associated macrophages. CONCLUSION: Our data clearly showed antitumor
      immunostimulatory activity of PSSC against transplanted H22 HCC cells.
      Suppressing tumor transplantation-induced PGE2 production was implicated in the
      anti-tumor immunostimulatory activity of PSSC. These works provides novel
      insights into the traditional application of S. chinensis against HCC and
      supported considering PSSC as an adjuvant reagent in clinical HCC treatment.

PMID- 25858512
TI  - miR-26a and miR-384-5p are required for LTP maintenance and spine enlargement.
AB  - Long-term potentiation (LTP) is a form of synaptic plasticity that results in
      enhanced synaptic strength. It is associated with the formation and enlargement
      of dendritic spines-tiny protrusions accommodating excitatory synapses. Both LTP
      and spine remodelling are crucial for brain development, cognition and the
      pathophysiology of neurological disorders. The role of microRNAs (miRNAs) in the
      maintenance of LTP, however, is not well understood. Using next-generation
      sequencing to profile miRNA transcriptomes, we demonstrate that miR-26a and miR
      384-5p specifically affect the maintenance, but not induction, of LTP and
      different stages of spine enlargement by regulating the expression of RSK3. Using
      bioinformatics, we also examine the global effects of miRNA transcriptome changes
      during LTP on gene expression and cellular activities. This study reveals a novel
      miRNA-mediated mechanism for gene-specific regulation of translation in LTP,
      identifies two miRNAs required for long-lasting synaptic and spine plasticity and
      presents a catalogue of candidate 'LTP miRNAs'. 

PMID- 25858514
TI  - Molecular mechanisms of the protective role of wheat germ oil against cyclosporin
      A-induced hepatotoxicity in rats.
AB  - CONTEXT: Cyclosporin A (CsA) is one of the most important immunosuppressive
      agents. However, its clinical use is strongly limited by several side effects
      including hepatotoxicity which remains a major clinical problem. Involvement of
      reactive oxygen species (ROS) in CsA-induced hepatotoxicity has been reported.
      OBJECTIVE: This study investigates the potential protective role of wheat germ
      oil (WGO) as an antioxidant against CsA-induced hepatotoxicity. MATERIALS AND
      METHODS: Twenty-four male Wistar albino rats (six animals in each group) received
      castor oil, the vehicle of CsA i.p. (control) or either CsA (25 mg/kg/d i.p.),
      WGO (900 mg/kg/d by oral gavage), or CsA in combination with WGO daily for 21 d.
      RESULTS: CsA administration significantly increased serum levels of the liver
      enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST). In
      addition, an increase in lipid peroxidation, inducible NO-synthase (iNOS), and NF
      kappaB expression were observed in hepatic tissues of CsA-alone-treated rats.
      Furthermore, significant reduction in the hepatic content of reduced glutathione
      (GSH), superoxide dismutase (SOD), and catalase (CAT) was also observed in CsA
      alone-treated animals. Moreover, histopathological changes occurred in CsA-alone
      treated rats. Concomitant administration of WGO along with CsA improved all these
      parameters. Most interestingly, the immunosuppressive effect of CsA was not
      affected by WGO. CONCLUSION: The present study suggests that concomitant use of
      WGO might be useful in reducing liver toxicity induced by CsA via inhibition of
      ROS, iNOS, and NF-kappaB expression.

PMID- 25858513
TI  - Evaluation of [(18)F]-(-)-norchlorofluorohomoepibatidine ([(18)F]-(-)-NCFHEB) as
      a PET radioligand to image the nicotinic acetylcholine receptors in non-human
      primates.
AB  - INTRODUCTION: The aims of the present study were to develop an optimized
      microfluidic method for the production of the selective nicotinic acetylcholine
      alpha4beta2 receptor radiotracer [(18)F]-(-)-NCFHEB ([(18)F]-Flubatine) and to
      investigate its receptor binding profile and pharmacokinetic properties in rhesus
      monkeys in vivo. METHODS: [(18)F]-(-)-NCFHEB was prepared in two steps, a
      nucleophilic fluorination followed by N-Boc deprotection. PET measurements were
      performed in rhesus monkeys including baseline and preblocking experiments with
      nicotine (0.24 mg/kg). Radiometabolites in plasma were measured using HPLC.
      RESULTS: [(18)F]-(-)-NCFHEB was prepared in a total synthesis time of 140 min.
      The radiochemical purity in its final formulation was >98% and the mean specific
      radioactivity was 97.3 +/- 16.1 GBq/MUmol (n = 6) at end of synthesis (EOS). In
      the monkey brain, radioactivity concentration was high in the thalamus, moderate
      in the putamen, hippocampus, frontal cortex, and lower in the cerebellum.
      Nicotine blocked 98-100% of [(18)F]-(-)-NCFHEB specific binding, and the non
      displaceable distribution volume (VND) was estimated at 5.9 +/- 1.0 mL/cm(3) (n =
      2), or 6.6 +/- 1.1 mL/cm(3) after normalization by the plasma free fraction fP.
      Imaging data are amenable to kinetic modeling analysis using the multilinear
      analysis (MA1) method, and model-derived binding parameters display good test
      retest reproducibility. In rhesus monkeys, [(18)F]-(-)-NCFHEB can yield robust
      regional binding potential (BPND) values (thalamus = 4.1 +/- 1.5, frontal cortex
      = 1.2 +/- 0.2, putamen = 0.96 +/- 0.45, and cerebellum = 0.10 +/- 0.29).
      CONCLUSION: An efficient microfluidic synthetic method was developed for
      preparation of [(18)F]-(-)-NCFHEB. PET examination in rhesus monkeys showed that
      [(18)F]-(-)-NCFHEB entered the brain readily and its regional radioactivity
      uptake pattern was in accordance with the known distribution of alpha4beta2
      receptors. Estimated non-displaceable binding potential (BPND) values in brain
      regions were better than those of [(18)F]2-FA and comparable to [(18)F]AZAN.
      These results confirm previous findings and support further examination of
      [(18)F]-(-)-NCFHEB in humans.

PMID- 25858515
TI  - Changing cell behaviours during beetle embryogenesis correlates with slowing of
      segmentation.
AB  - Segmented animals are found in major clades as phylogenetically distant as
      vertebrates and arthropods. Typically, segments form sequentially in what has
      been thought to be a regular process, relying on a segmentation clock to pattern
      budding segments and posterior mitosis to generate axial elongation. Here we show
      that segmentation in Tribolium has phases of variable periodicity during which
      segments are added at different rates. Furthermore, elongation during a period of
      rapid posterior segment addition is driven by high rates of cell rearrangement,
      demonstrated by differential fates of marked anterior and posterior blastoderm
      cells. A computational model of this period successfully reproduces elongation
      through cell rearrangement in the absence of cell division. Unlike current models
      of steady-state sequential segmentation and elongation from a proliferative
      growth zone, our results indicate that cell behaviours are dynamic and variable,
      corresponding to differences in segmentation rate and giving rise to
      morphologically distinct regions of the embryo. 

PMID- 25858516
TI  - Effect of ethnicity on first trimester biomarkers for combined trisomy 21
      screening: results from a multicenter study in six Asian countries.
AB  - OBJECTIVE: To assess differences between first trimester trisomy 21 screening
      markers free beta chain of the human chorionic gonadotrophin (betahCG) and
      pregnancy-associated plasma protein A (PAPP-A) in pregnant women of six different
      Asian countries (China, Indonesia, Korea, Taiwan, Thailand, and Vietnam) and
      compare serum levels with those in women of European countries. METHODS: Median
      and multiple of median (MoM) values of free betahCG and PAPP-A were determined in
      more than 3000 pregnant women from the Asian countries during their first
      trimester of pregnancy. Differences in MoM values between a European reference
      group from a previous multicenter evaluation and the Asian population were
      evaluated. Two different types of population correction factors for T21 risk
      estimation were assessed. RESULTS: An at least 10% difference of median MoMs
      between European and Asian PAPP-A values was found to be statistically
      significant (p < 0.0001). The specificity of the screening did not show a big
      difference in individual countries, when using the country-specific correction
      factor compared with the overall Asian correction factor (<1.4%). CONCLUSIONS:
      The use of a correction factor is recommended based on the differences in
      European and Asian MoM values. Developing country-specific medians in larger
      study populations can help identify clinical relevant differences and give the
      opportunity to explore a more accurate risk calculation.

PMID- 25858517
TI  - Length of hospital stay and discharge disposition in older trauma patients.
AB  - As the number of older adults increases and life expectancies are increasing,
      more incidences of traumatic injury are expected in this population. In this
      study, the relationships between demographic variables, pain, days from admission
      to therapy evaluation, length of stay and discharge disposition were examined in
      132 older adults who had experienced a traumatic event. Results showed that
      significant relationships existed between pain, age, comorbidities, injury
      severity and days from admission to therapy evaluation and length of stay; those
      with less pain, greater age and had more days between admission and when the
      first therapy evaluation occurred had longer lengths of stay. In addition,
      demographic variables, overall length of stay and pain intensity during therapy
      were associated with discharge location; for longer lengths of stay and higher
      pain, older trauma patients were less likely to be discharged to home. 

PMID- 25858518
TI  - Low health literacy in older women: the influence of patient-clinician
      relationships.
AB  - One in five individuals living in the United States has deficient literacy
      skills, contributing to challenges navigating a complex health system. Low health
      literacy is a burden to individuals and to society, with global implications to
      the most vulnerable, including older women. Findings of this qualitative study
      support the current literature in that health literacy is a social commodity
      bound to health care access, health promotion, health protection and disease
      prevention. New insights highlight the importance of the patient-clinician
      relationship and a focus on patient-centered care to identify and address health
      literacy needs. Essential themes identified by participants as requisite to
      working with low literacy older females are time, relationships, communication,
      education, and empowerment. Although each may be viewed independently, their
      overlapping was recognized as key to optimizing health, and of this list,
      relationships and communication were identified as critical to enhancing minimal
      health literacy in the clinical setting. 

PMID- 25858519
TI  - Long-term safety of proton pump inhibitor therapy assessed under controlled,
      randomised clinical trial conditions: data from the SOPRAN and LOTUS studies.
AB  - BACKGROUND: Control of chronic gastro-oesophageal reflux disease may be achieved
      either by anti-reflux surgery (ARS) or by long-term medical therapy with proton
      pump inhibitors (PPIs). The primary efficacy results of the SOPRAN study,
      comparing long-term omeprazole use with open ARS, and the LOTUS study, comparing
      long-term esomeprazole use with laparoscopic ARS, have been reported. A secondary
      objective of these studies was to address the long-term safety of these
      respective therapeutic strategies and thereby provide a valid scientific platform
      for assessing long-term PPI safety. AIM: To assess the safety of long-term PPI
      therapy with omeprazole and esomeprazole through analyses of data from the
      randomised SOPRAN and LOTUS studies. METHODS: Safety data were collected from
      patients during the 12-year period of the SOPRAN study (n = 298) and the 5-year
      period of the LOTUS study (n = 514). Reported serious adverse events (SAEs) and
      changes in laboratory variables were analysed. RESULTS: Across both studies, SAEs
      were reported at a similar frequency in the PPI and ARS treatment groups. Taking
      the time frames into consideration, the number of fatal SAEs in the two studies
      was low in both treatment groups. Laboratory results, including routine
      haematology and tests for liver enzymes, electrolytes, vitamin D, vitamin B12 ,
      folate and homocysteine, showed no clinically relevant changes over time. As
      expected, gastrin and chromogranin A were elevated in the PPI groups, with the
      greatest increases observed in the first year. CONCLUSION: No major safety
      concerns arose during 5-12 years of continuous PPI therapy. (ClinicalTrials.gov:
      NCT00251927 and NCT00256737).

PMID- 25858520
TI  - Early post-transplant survival: Interaction of MELD score and hospitalization
      status.
AB  - BACKGROUND & AIMS: Urgency-based allocation that relies on the MELD score
      prioritizes patients at the highest risk of waitlist mortality. However,
      identifying patients at greatest risk for short-term post-transplant mortality is
      needed in order to optimize the potential gains in overall survival obtained
      through improved long-term management of transplant recipients. There are limited
      data on the predictive ability of MELD score for early post-transplant mortality,
      and no data assessing the interaction between MELD score and hospitalization
      status. METHODS: We analyzed UNOS data from 2002 to 2013 on 50,838 non-status 1
      single-organ liver transplant recipients and fit multivariable logistic models to
      evaluate the association and interaction between MELD score and pre-transplant
      hospitalization status on short-term post-transplant mortality. RESULTS: There
      was a significant interaction (p<0.01) between laboratory MELD score and
      hospitalization status on three-, six-, and 12-month post-transplant mortality in
      multivariable logistic models. This interaction was most pronounced in patients
      with a laboratory MELD score <25 transplanted from an ICU, whose adjusted
      predicted three-, six-, and 12-month post-transplant mortality approximated those
      of patients with a MELD score ?30. Compared to hospitalized patients with a MELD
      score of 30-34, those with a MELD score ?35 in an ICU had significantly increased
      risk of three-month (OR: 1.54, 95% CI: 1.21-1.97), 6-month (OR: 1.35, 95% CI:
      1.09-1.67), and 12-month (OR: 1.25, 95% CI: 1.03-1.52) post-transplant mortality.
      DISCUSSION: Pre-transplant ICU status modifies the risk of early post-transplant
      mortality, independent of MELD score. This should be considered when determining
      candidacy for transplantation in order to optimize efficient use of a scarce
      resource.

PMID- 25858521
TI  - The prevalence of pineal cyst in patients with cerebral palsy.
AB  - PURPOSE: Pineal cysts are common incidental findings during magnetic resonance
      imaging (MRI) examinations. The etiology of pineal cyst development is still
      unclear. We aimed to determine whether there is an association between
      periventricular leukomalacia and pineal cyst prevalence. METHODS: Clinical and
      MRI data of 201 patients with periventricular leukomalacia (110 female, 91 male;
      mean age, 6 years; range, 2-18 years) and 687 control patients (355 female, 332
      male; mean age, 6 years  range, 2-18 years) who did not have any evidence of
      periventricular leukomalacia were independently evaluated by two radiologists for
      presence or absence of pineal cyst. RESULTS: Pineal cysts were detected in 32.3%
      of the study group (65/201) and 8.4% of the control group (58/687) (P < 0.001).
      Patients with periventricular leukomalacia were more likely to have a pineal
      cyst. In terms of pineal cyst detection on MRI, interobserver reliability was
      high between the two radiologists. CONCLUSION: The prevalence of pineal cysts is
      higher in patients with periventricular leukomalacia. We suggest that an ischemic
      process may have a role in the etiopathogenesis of pineal cyst development.

PMID- 25858522
TI  - Direct aneurysm sac catheterization and embolization of an enlarging internal
      iliac aneurysm using cone-beam CT.
AB  - Since cone-beam computed tomography (CT) has been adapted for use with a C-arm
      system it has brought volumetric CT capabilities in the interventional suite.
      Although cone-beam CT image resolution is far inferior to that generated by
      traditional CT scanners, the system offers the ability to place an access needle
      into position under tomographic guidance and use the access to immediately begin
      a fluoroscopic procedure without moving the patient. We describe a case of a
      "jailed" enlarging internal iliac artery aneurysm secondary to abdominal aortic
      aneurysm repair, in which direct percutaneous puncture of the internal iliac
      artery aneurysm sac was performed under cone-beam CT guidance. 

PMID- 25858523
TI  - Shear wave elastography of placenta: in vivo quantitation of placental elasticity
      in preeclampsia.
AB  - PURPOSE: We aimed to evaluate the utility of shear wave elastography (SWE) for
      assessing the placenta in preeclampsia disease. METHODS: A total of 50 pregnant
      women in the second or third trimester (23 preeclampsia patients and 27 healthy
      control subjects) were enrolled in the study. Obstetrical grayscale and Doppler
      ultrasonography, SWE findings of placenta, and prenatal/postnatal clinical data
      were analyzed and the best SWE cutoff value which represents the diagnosis of
      preeclampsia was determined. Sensitivity, specificity, positive predictive value
      (PPV), negative predictive value (NPV), and diagnostic accuracy of preeclampsia
      were calculated based on SWE measurements. RESULTS: Mean stiffness values were
      much higher in preeclamptic placentas in all regions and layers than in normal
      controls. The most significant difference was observed in the central placental
      area facing the fetus where the umbilical cord inserts, with a median of 21 kPa
      (range, 3-71 kPa) for preeclampsia and 4 kPa (range, 1.5-14 kPa) for the control
      group (P < 0.01). The SWE data showed a moderate correlation with the uterine
      artery resistivity and pulsatility indices. The cutoff value maximizing the
      accuracy of diagnosis was 7.35 kPa (area under curve, 0.895; 95% confidence
      interval, 0.791-0.998); sensitivity, specificity, PPV, NPV, and accuracy were
      90%, 86%, 82%, 92%, and 88%, respectively. CONCLUSION: Stiffness of the placenta
      is significantly higher in patients with preeclampsia. SWE appears to be an
      assistive diagnostic technique for placenta evaluation in preeclampsia.

PMID- 25858524
TI  - Risk factors associated with late aneurysmal sac expansion after endovascular
      abdominal aortic aneurysm repair.
AB  - PURPOSE: We aimed to identify the risk factors associated with late aneurysmal
      sac expansion after endovascular abdominal aortic aneurysm repair (EVAR).
      METHODS: We retrospectively reviewed contrast-enhanced computed tomography (CT)
      images of 143 patients who were followed for >=6 months after EVAR. Sac expansion
      was defined as an increase in sac diameter of 5 mm relative to the preoperative
      diameter. Univariate and multivariate analyses were performed to identify
      associated risk factors for late sac expansion after EVAR from the following
      variables: age, gender, device, endoleak, antiplatelet therapy, internal iliac
      artery embolization, and preprocedural variables (aneurysm diameter, proximal
      neck diameter, proximal neck length, suprarenal neck angulation, and infrarenal
      neck angulation). RESULTS: Univariate analysis revealed female gender, endoleak,
      aneurysm diameter >=60 mm, suprarenal neck angulation >45 degrees , and
      infrarenal neck angulation >60 degrees  as factors associated with sac expansion.
      Multivariate analysis revealed endoleak, aneurysm diameter >=60 mm, and
      infrarenal neck angulation >60 degrees  as independent predictors of sac
      expansion (P < 0.05, for all). CONCLUSION: Our results suggest that patients with
      small abdominal aortic aneurysms (<60 mm) and infrarenal neck angulation <=60
      degrees  are more favorable candidates for EVAR. Intraprocedural treatments, such
      as prophylactic embolization of aortic branches or intrasac embolization, may
      reduce the risk of sac expansion in patients with larger abdominal aortic
      aneurysms or greater infrarenal neck angulation.

PMID- 25858525
TI  - MRI-guided core needle biopsy of the prostate: acceptance and side effects.
AB  - PURPOSE: We aimed to study side effects, complications, and patient acceptance of
      magnetic resonance imaging-guided real-time biopsy (MRI-GB) of the prostate.
      METHODS: Fifty-four men (49-78 years) with elevated prostate-specific antigen
      after at least one negative systematic transrectal ultrasound-guided biopsy (TRUS
      GB) were included in a prospective clinical study. Suspicious areas on images
      were selectively sampled by obtaining a median of four specimens (range, 1-9
      specimens) using MRI-GB. In TRUS-GB, a median of 10 specimens (range, 6-14
      specimens) were obtained. Telephone interviews were conducted one week after
      outpatient MRI-GB, asking patients about pain and side effects (hematuria,
      hemospermia, rectal bleeding, fever, and chills) of the two biopsy procedures and
      which of the two procedures they preferred. Multinomial regression analysis and
      Fisher's exact test was used to test for differences. RESULTS: MRI-GB was
      preferred by 65% (35/54), and 82% (44/54) would undergo MRI-GB again. Pain
      intensity (P = 0.005) and bleeding duration (P = 0.004) were significantly lower
      for MRI-GB compared with TRUS-GB. Hematuria was less common after MRI-GB compared
      with TRUS-GB (P = 0.006). A high correlation was given between bleeding intensity
      and bleeding duration for TRUS-GB (r=0.77) and pain intensity and pain duration
      for MRI-GB (r=0.65). Although hemospermia, rectal hemorrhage, fever, and chills
      were less common in MRI, they showed no statistically significant difference.
      CONCLUSION: MRI-GB of the prostate seems to have fewer side effects and less pain
      intensity than TRUS-GB and was preferred by the majority of patients.

PMID- 25858526
TI  - Preoperative arterial embolization of large liver hemangiomas.
AB  - PURPOSE: We aimed to investigate the efficacy and safety of preoperative
      selective intra-arterial embolization (PSIAE) in the surgical treatment of large
      liver hemangiomas. METHODS: Data of 22 patients who underwent resection of large
      liver hemangiomas were retrospectively analyzed. PSIAE was performed in cases
      having a high risk of severe blood loss during surgery (n=11), while it was not
      applied in cases with a low risk of blood loss (n=11). RESULTS: A total of 19
      enucleations and six anatomic resections were performed. Operative time,
      intraoperative bleeding amount, Pringle period, and blood transfusion were
      comparable between the two groups (P > 0.05, for all). The perioperative serum
      aspartate transaminase level was not different between groups (P = 1.000).
      Perioperative total bilirubin levels were significantly increased in the PSIAE
      group (P = 0.041). Postoperative hospital stay was longer in the PSIAE group.
      Surgical complications were comparable between groups (P = 0.476). CONCLUSION:
      Patients who underwent PSIAE due to a high risk of severe blood loss during
      resection of large liver hemangiomas had comparable operative success as patients
      with a low risk of blood loss who were operated without PSIAE. Hence, PSIAE can
      be used for the control of intraoperative blood loss, especially in surgically
      difficult cases.

PMID- 25858527
TI  - Therapeutic effects of transarterial infusion of lipiodol and ethanol in various
      ratios in a rabbit VX2 tumor model.
AB  - PURPOSE: We aimed to evaluate the therapeutic effect and safety of transcatheter
      arterial embolization with various volume ratios of lipiodol and ethanol in a
      rabbit VX2 tumor model to identify the optimal volume ratio. METHODS: Eighteen
      adult male New Zealand white rabbits implanted with VX2 tumors in their left
      liver lobes were randomly divided into six groups based on volume ratios of
      lipiodol to ethanol: group A, 3:1; group B, 2:1; group C, 1:1; group D, 1:2;
      group E, 1:3; and group F, 1:4. Pre- and post-treatment unenhanced magnetic
      resonance imaging was used to detect tumor formation and evaluate tumor growth
      rates. Liver samples were harvested one week after the procedure, and apoptosis
      index of tumor tissues was evaluated by pathologic examination and TUNEL assay.
      RESULTS: Tumor size decreased in groups B, C, and D, but increased in groups A,
      E, and F. Tumor growth rates in groups A-F were 0.40+/-0.03, -0.11+/-0.21, 
      0.08+/-0.09, -0.12+/-0.07, 0.06+/-0.12, and 0.05+/-0.09, respectively. The change
      in tumor size was significantly different in group A compared with the rest of
      the groups, but no significant difference was observed among groups B-F.
      Apoptosis indexes of the six groups were 4.7+/-2.1%, 6.7+/-2.1%, 11.7+/-3.1%,
      11.0+/-2.0%, 10.7+/-3.2%, and 12+/-3%, respectively. Apoptosis index was
      significantly lower in group A compared with groups C-F (P < 0.05). Apoptosis
      index of group B was significantly lower than groups C and F. There was no
      significant difference among the other groups. CONCLUSION: The volume ratios of
      lipiodol to ethanol ranging from 2:1 to 1:4 were equally effective, the ratios
      2:1 and 1:3 had equal safety, and the ratios 1:1 and 1:2 indicated better long
      term therapeutic effect. Increasing ethanol in the mixture caused more severe
      liver injury. Optimal efficacy and safety was achieved with a lipiodol to ethanol
      volume ratio of 1:1.

PMID- 25858528
TI  - Three-dimensional coronary dark-blood interleaved with gray-blood (cDIG) magnetic
      resonance imaging at 3 tesla.
AB  - PURPOSE: Three-dimensional (3D) dark-blood MRI has shown great potential in
      coronary artery plaque evaluation. However, substantial variability in
      quantification could result from superficial calcification because of its low
      signal. To address this issue, a 3D coronary dark-blood interleaved with gray
      blood (cDIG) technique was developed. METHODS: cDIG is based on a balanced steady
      state free precession readout combined with a local re-inversion-based double
      inversion-recovery (LocReInv-DIR) preparation. The LocReInv-DIR is applied every
      two RR intervals. Dark-blood and gray-blood contrasts are collected in the first
      and second RR interval, respectively. To improve the respiratory gating
      efficiency, two independent navigators were developed to separately gate the
      respiratory motion for the two interleaved acquisitions. In vivo experiments in
      eight healthy subjects and one patient were conducted to validate the technique.
      RESULTS: cDIG provided dual-contrasts without compromise in scan time. The dark
      blood images with cDIG demonstrated excellent wall and lumen signal performances
      and morphological measurements. Advantageously, cDIG yielded a second contrast
      that was shown to help identify the superficial calcification in the coronary
      plaque of a patient. CONCLUSION: A novel technique was developed for obtaining 3D
      coronary vessel wall and gray lumen images. The additional contrast may aid in
      identifying calcified nodules and thus potentially improve the evaluation of
      coronary plaque burden.

PMID- 25858530
TI  - Subcutaneous transplantation promotes organ formation of the fetal rat urogenital
      sinus.
AB  - The aim of this study is to develop a novel experimental model of the
      subcutaneous transplantation of fetal urogenital sinus (UGS) into normal and
      castrated adult male rats for the pathophysiological investigation of the normal
      and developing prostate. Fetal UGS obtained from 20-day-old male rat embryos was
      subcutaneously transplanted into 7-week-old normal and castrated male rats. We
      observed the growth pattern, histopathological characteristics and
      immunohistochemical localization of cytokeratin 5 (CK 5), cytokeratin 8 (CK 8)
      and androgen receptor (AR) in the transplanted tissues. Almost all of the
      transplanted UGS organs gradually increased in weight over time in the non
      castrated recipient animals, and the histopathological observations and
      immunohistochemical analysis of CK 5 and CK 8 revealed that the morphological
      changes in the tissues were in accordance with the features of normal prostate
      development. The histological characteristics included glandular epithelial
      dominant and stromal dominant area, with an increase in the glandular epithelial
      dominant areas over time and resemblance among a portion of the transplanted
      tissues within a certain period during the developmental course to the
      histopathology of human benign prostatic hyperplasia (BPH). The effects of
      androgens and resemblance in the immunohistochemical localization pattern changes
      in AR to that observed in the normal differentiating rat prostate were also
      noted. We conclude that the subcutaneous space provides an adequate
      microenvironment for UGS growth. 

PMID- 25858529
TI  - Advanced protein formulations.
AB  - It is well recognized that protein product development is far more challenging
      than that for small-molecule drugs. The major challenges include inherent
      sensitivity to different types of stresses during the drug product manufacturing
      process, high rate of physical and chemical degradation during long-term storage,
      and enhanced aggregation and/or viscosity at high protein concentrations. In the
      past decade, many novel formulation concepts and technologies have been or are
      being developed to address these product development challenges for proteins.
      These concepts and technologies include use of uncommon/combination of
      formulation stabilizers, conjugation or fusion with potential stabilizers, site
      specific mutagenesis, and preparation of nontraditional types of dosage forms
      semiaqueous solutions, nonfreeze-dried solid formulations, suspensions, and other
      emerging concepts. No one technology appears to be mature, ideal, and/or adequate
      to address all the challenges. These gaps will likely remain in the foreseeable
      future and need significant efforts for ultimate resolution. 

PMID- 25858531
TI  - A journey through the pituitary gland: Development, structure and function, with
      emphasis on embryo-foetal and later development.
AB  - The pituitary gland and the hypothalamus are morphologically and functionally
      associated in the endocrine and neuroendocrine control of other endocrine glands.
      They therefore play a key role in a number of regulatory feedback processes that
      co-ordinate the whole endocrine system. Here we review the neuroendocrine system,
      from the discoveries that led to its identification to some recently clarified
      embryological, functional, and morphological aspects. In particular we review the
      pituitary gland and the main notions related to its development, organization,
      cell differentiation, and vascularization. Given the crucial importance of the
      factors controlling neuroendocrine system development to understand parvocellular
      neuron function and the aetiology of the congenital disorders related to
      hypothalamic-pituitary axis dysfunction, we also provide an overview of the
      molecular and genetic studies that have advanced our knowledge in the field.
      Through the action of the hypothalamus, the pituitary gland is involved in the
      control of a broad range of key aspects of our lives: the review focuses on the
      hypothalamic-pituitary-gonadal axis, particularly GnRH, whose abnormal secretion
      is associated with clinical conditions involving delayed or absent puberty and
      reproductive dysfunction. 

PMID- 25858532
TI  - Wilms' tumor 1 (WT1) protein expression in human developing tissues.
AB  - Several genes playing crucial roles in human development often reproduce a key
      role also during the onset and progression of malignant tumors. WT1, a
      transcription factor expressed with a dynamic pattern during human development,
      has either oncogenic or suppressor tumor properties. A detailed analysis of the
      immunohistochemical profile of WT1 protein in human developmental tissues could
      be exploitable as the rational for better understanding its role in
      cancerogenesis and planning innovative WT1-based therapeutic approaches. This
      review focuses on the dynamic immunohistochemical expression and distribution of
      WT1 protein during human ontogenesis, providing illustrations and discussion on
      the most relevant findings. The possibility that WT1 nuclear/cytoplasmic
      expression in some tumors mirrors its normal developmental regulation will be
      emphasized. 

PMID- 25858533
TI  - Should we administrate anticoagulants to critically ill patients with new onset
      supraventricular arrhythmias?

PMID- 25858534
TI  - Type 2 diabetes mellitus and atrial fibrillation: From mechanisms to clinical
      practice.
AB  - Type 2 diabetes mellitus is one of the most common chronic conditions and its
      prevalence has increased continuously over the past decades, primarily due to the
      obesity epidemic. Atrial fibrillation (AF) is the most frequent sustained cardiac
      arrhythmia in clinical practice and is associated with increased cardiovascular
      and cerebrovascular morbidity and mortality. Recent studies have shown that
      patients with diabetes have an increased risk of AF. However, the results about
      the relationship between diabetes and AF are still conflicting. Mechanisms that
      are responsible for an association between diabetes and AF, as well as the
      adequate treatment of AF in patients with diabetes, are still insufficiently
      studied. The aim of this review is to summarize the current knowledge of
      mechanisms that connect AF and diabetes, the clinical studies that include
      patients with both conditions, and the treatment options in modern pharmacology. 

PMID- 25858535
TI  - Reliability of a Bayesian network to predict an elevated aldosterone-to-renin
      ratio.
AB  - BACKGROUND: Resistant hypertension is common, mainly idiopathic, but sometimes
      related to primary aldosteronism. Thus, most hypertension specialists recommend
      screening for primary aldosteronism. AIMS: To optimize the selection of patients
      whose aldosterone-to-renin ratio (ARR) is elevated from simple clinical and
      biological characteristics. METHODS: Data from consecutive patients referred
      between 1 June 2008 and 30 May 2009 were collected retrospectively from five
      French 'European excellence hypertension centres' institutional registers.
      Patients were included if they had at least one of: onset of hypertension before
      age 40 years, resistant hypertension, history of hypokalaemia, efficient
      treatment by spironolactone, and potassium supplementation. An ARR>32 ng/L and
      aldosterone>160 ng/L in patients treated without agents altering the renin
      angiotensin system was considered as elevated. Bayesian network and stepwise
      logistic regression were used to predict an elevated ARR. RESULTS: Of 334
      patients, 89 were excluded (31 for incomplete data, 32 for taking agents that
      alter the renin-angiotensin system and 26 for other reasons). Among 245 included
      patients, 110 had an elevated ARR. Sensitivity reached 100% or 63.3% using
      Bayesian network or logistic regression, respectively, and specificity reached
      89.6% or 67.2%, respectively. The area under the receiver-operating
      characteristic curve obtained with the Bayesian network was significantly higher
      than that obtained by stepwise regression (0.93+/-0.02 vs. 0.70+/-0.03; P<0.001).
      CONCLUSION: In hypertension centres, Bayesian network efficiently detected
      patients with an elevated ARR. An external validation study is required before
      use in primary clinical settings.

PMID- 25858536
TI  - End-systolic wall stress predicts post-discharge heart failure after acute
      myocardial infarction.
AB  - BACKGROUND: Compensatory mechanisms activated after myocardial infarction include
      an increase in systolic wall stress (SWS) and activation of the neurohormonal
      system. Nevertheless, left ventricular ejection fraction (LVEF) and infarct size
      are the established primary predictors of outcome after ST-segment elevation
      myocardial infarction. AIMS: To assess the relative impact of various cardiac
      magnetic resonance (CMR) imaging variables, such as infarct size, LVEF and SWS,
      on pre- and post-discharge heart failure (HF). METHODS: CMR was performed in a
      prospective study involving 169 patients with first ST-segment elevation
      myocardial infarction. Common CMR findings, such as SWS, were computed. RESULTS:
      Mean SWS was 16.3+/-5.1*10(3)N.m(-2), and was systematically higher in patients
      exhibiting either pre- or post-discharge HF (18.9+/-5.7 and 21.3+/-7.6*10(3) N.m(
      2), respectively). SWS was moderately related to initial infarct size (r=0.405; P
      <0.001). In total, 28 patients presented with HF during the hospitalization phase
      and 14 during follow-up, with a median time of event of 93 days (25th-75th
      percentiles, 29-139.25 days). The univariate predictors of HF were age, LVEF,
      infarct size, SWS, microvascular obstruction, anterior infarction and heart rate
      at admission. Multivariable analysis revealed infarct size and age to be the
      predictors of predischarge HF, while SWS and heart rate at admission predicted
      post-discharge HF. The greatest SWS quartile provided a negative predictive value
      of 95.9%. CONCLUSION: Regardless of LVEF and infarct size, SWS was shown to be an
      independent predictor of post-discharge HF after ST-segment elevation myocardial
      infarction.

PMID- 25858537
TI  - Eosinophilic cardiac disease: Molecular, clinical and imaging aspects.
AB  - Eosinophilia may be responsible for cardiac injuries of widely varying severity,
      from acute myocarditis to endomyocardial fibrosis. In this review, we present
      both the molecular mechanisms that are responsible for these lesions and their
      clinical and paraclinical aspects. Numerous aetiologies can lead to severe
      eosinophilia, but these are mainly represented by hypersensitivity reactions,
      rheumatological diseases and hypereosinophilic syndrome. Because cardiac
      involvement may be extremely severe, echocardiography should be always performed
      in the context of eosinophilia and appropriate therapeutics should be started
      rapidly in order to limit the progression of the disease. 

PMID- 25858538
TI  - Factors predicting Sprint Fidelis lead fracture: Results at 5 years from a French
      multicentre registry.
AB  - BACKGROUND: The small diameter Sprint Fidelis defibrillation lead has not been
      implanted in patients since 2007 due to its unusually high rate of fracture.
      Predictors of lead fracture risk were identified in several studies, mainly in
      North American studies. AIM: We established a multicentre registry to determine
      the lead fracture rate and predictors of fracture in a large cohort of French
      patients. METHODS: Nine hundred and eighty-six patients implanted with a Sprint
      Fidelis lead at six centres between December 2004 and November 2007 were included
      in this registry. RESULTS: Over a mean follow-up of 51.4+/-20 months, the mean
      fracture rate was 11.2%, and increased over time: 1.2% at 1 year, 3.8% at 2
      years, 7.4% at 3 years, 13.9% at 4 years, and 20.7% at 5 years. In multivariable
      analysis, younger age (<40 years) was associated with a higher risk of fracture
      compared to patients<40 years, patients aged between 40-60 years had a relative
      risk of 0.53 (95% confidence interval [CI] 0.29-0.98) and patients>60 years had a
      relative risk of 0.45 (95% CI 0.24-0.84) and subpectoral implantation (at 3
      years) with a relative risk of 2.35 (95% CI 1.29-4.28). Lead model 6930 (single
      coil, passive-fixation) had a relative risk of 3.47 (95% CI 1.13-10.7) compared
      with the 6949 model (double coil, active-fixation). No other predictor of
      fracture was identified. CONCLUSIONS: In a large multicentre cohort of French
      patients implanted with a Sprint Fidelis electrode, the fracture rate remains
      high, especially in young patients with submuscular implant and the 6930
      electrode model.

PMID- 25858539
TI  - Prevalence and correlates of non-optimal secondary medical prevention in patients
      with stable coronary artery disease.
AB  - BACKGROUND: In patients with coronary artery disease (CAD), non-optimal use of
      evidence-based medications is associated with an increased risk of adverse
      outcome. AIMS: To assess the prevalence and correlates of non-optimal secondary
      medical prevention in patients with stable CAD. METHODS: We included 4184
      consecutive outpatients with stable CAD. Treatment at inclusion was classified as
      optimal/non-optimal regarding the four major classes of secondary prevention
      drugs: antithrombotics; statins; angiotensin-converting enzyme (ACE) inhibitors
      or angiotensin II receptor blockers (ARBs); and beta-blockers. For each
      treatment, the prescription was considered non-optimal if the drug was missing
      despite a class IA indication according to international guidelines. To assess
      the information globally, non-optimal secondary prevention was defined as at
      least one major treatment missing. RESULTS: The proportions of patients with non
      optimal treatment were 0.7%, 7.8%, 12.9% and 10.3% for antithrombotics, statins,
      ACE inhibitors/ARBs and beta-blockers, respectively. Non-optimal secondary
      medical prevention was observed in 16.8% of cases. By multivariable analysis, the
      correlates of non-optimal secondary medical prevention were long time interval
      since last coronary event (P<0.0001), older age (P<0.0001), diabetes mellitus
      (P<0.0001), hypertension (P<0.0001), no history of myocardial infarction
      (P=0.001), no history of coronary revascularization (P=0.013) and low glomerular
      filtration rate (P=0.042). CONCLUSIONS: Although most patients with stable CAD
      are receiving evidence-based medications according to guidelines, there remain
      subgroups at higher risk of non-optimal treatment. In particular, it might be
      feasible to improve prevention by focusing on patients in whom a long time has
      elapsed since the last coronary event.

PMID- 25858540
TI  - Effects of germination on the nutritional properties, phenolic profiles, and
      antioxidant activities of buckwheat.
AB  - Germination is considered to be an effective process for improving the
      nutritional quality and functionality of cereals. In this study, changes of
      nutritional ingredients, antinutritional components, chemical composition, and
      antioxidant activities of buckwheat seeds over 72 h of germination were
      investigated, and the reasons for these changes are discussed. With the prolonged
      germination time, the contents of crude protein, reducing sugar, total phenolics,
      total flavonoids, and condensed tannins increased significantly, while the levels
      of crude fat, phytic acid, and the activity of trypsin inhibitor decreased.
      Phenolic compounds, such as rutin, vitexin, isovitexin, orientin, isoorientin,
      chlorogenic acid, trans-3-hydroxycinnamic acid, and p-hydroxybenzoic acid
      increased significantly during the germination process, which may be due to the
      activation of phenylalanine ammonialyase. The improvement of flavonoids led to
      significant enhancement of the antioxidant activities of germinated buckwheat.
      Germinated buckwheat had better nutritional value and antioxidant activities than
      ungerminated buckwheat, and it represented an excellent natural source of
      flavonoids and phenolic compounds, especially rutin and C-glycosylflavones.
      Therefore, germinated buckwheat could be used as a promising functional food for
      health promotion. 

PMID- 25858542
TI  - Silver salts and DBU cooperatively catalyzed nucleophilic addition/cyclization of
      propargylic alcohols with trifluoromethyl ketones.
AB  - A general and efficient synthesis of trifluoromethyl substituted 5-alkylidene-1,3
      dioxolane using a silver salt and DBU cooperatively catalyzed nucleophilic
      addition/cyclization of propargylic alcohols and trifluoromethyl ketones is
      described. The procedure produced 5-alkylidene-1,3-dioxolane derivatives with
      good to excellent yields and can be used with a broad range of substrates. 

PMID- 25858541
TI  - The Nurr1 Activator 1,1-Bis(3'-Indolyl)-1-(p-Chlorophenyl)Methane Blocks
      Inflammatory Gene Expression in BV-2 Microglial Cells by Inhibiting Nuclear
      Factor kappaB.
AB  - NR4A family orphan nuclear receptors are an important class of transcription
      factors for development and homeostasis of dopaminergic neurons that also inhibit
      expression of inflammatory genes in glial cells. The identification of NR4A2
      (Nurr1) as a suppressor of nuclear factor kappaB (NF-kappaB)-related
      neuroinflammatory genes in microglia and astrocytes suggests that this receptor
      could be a target for pharmacologic intervention in neurologic disease, but
      compounds that promote this activity are lacking. Selected diindolylmethane
      compounds (C-DIMs) have been shown to activate or inactivate nuclear receptors,
      including Nurr1, in cancer cells and also suppress astrocyte inflammatory
      signaling in vitro. Based upon these data, we postulated that C-DIM12 [1,1-bis(3'
      indolyl)-1-(p-chlorophenyl) methane] would suppress inflammatory signaling in
      microglia by a Nurr1-dependent mechanism. C-DIM12 inhibited lipopolysaccharide
      (LPS)-induced expression of NF-kappaB-regulated genes in BV-2 microglia including
      nitric oxide synthase (NOS2), interleukin-6 (IL-6), and chemokine (C-C motif)
      ligand 2 (CCL2), and the effects were attenuated by Nurr1-RNA interference.
      Additionally, C-DIM12 decreased NF-kappaB activation in NF-kappaB-GFP (green
      fluorescent protein) reporter cells and enhanced nuclear translocation of Nurr1
      primary microglia. Chromatin immunoprecipitation assays indicated that C-DIM12
      decreased lipopolysaccharide-induced p65 binding to the NOS2 promoter and
      concurrently enhanced binding of Nurr1 to the p65-binding site. Consistent with
      these findings, C-DIM12 also stabilized binding of the Corepressor for Repressor
      Element 1 Silencing Transcription Factor (CoREST) and the Nuclear Receptor
      Corepressor 2 (NCOR2). Collectively, these data identify C-DIM12 as a modulator
      of Nurr1 activity that results in inhibition of NF-kappaB-dependent gene
      expression in glial cells by stabilizing nuclear corepressor proteins, which
      reduces binding of p65 to inflammatory gene promoters. 

PMID- 25858543
TI  - A novel technique for diaphragm biopsies in human patients.
AB  - BACKGROUND: The diaphragm is difficult to biopsy because of its anatomic
      location. We describe a new laparoscopic diaphragm biopsy technique. MATERIAL AND
      METHODS: Fifty one patients with amyotrophic lateral sclerosis gave their consent
      to diaphragm biopsy in the context of an implanted phrenic nerve stimulation
      protocol (NCT01583088). The biopsy was taken from the costal diaphragm, after
      opening the parietal peritoneum with scissors, and by grasping the diaphragmatic
      muscle over the rib with toothed laparoscopy forceps. RESULTS: The first four
      electrocoagulation biopsies were unsuitable for morphologic examination. The
      following 47 biopsies were therefore performed without electrocoagulation. The
      mean size of the biopsy fragments obtained after preparation was 3 +/- 1 * 2 +/-
      1 * 1 +/- 1 mm (maximum: 4 * 3 * 2 mm). A diaphragmatic injury occurred during
      the section in three cases requiring immediate suture without causing
      pneumothorax. A small pleural effusion was observed on the postoperative chest x
      ray in one patient with a spontaneously favorable outcome. Numerous stains were
      able to be performed on the fragments obtained. CONCLUSIONS: Diaphragm biopsy can
      be safely performed by laparoscopy and yields tissue suitable for our future
      histologic evaluation.

PMID- 25858544
TI  - Simulation-based end-of-life care training during surgical clerkship: assessment
      of skills and perceptions.
AB  - BACKGROUND: Assessment of interpersonal and psychosocial competencies during end
      of-life care training is essential. This study reports the relationship between
      simulation-based end-of-life care Objective Structured Clinical Examination
      ratings and communication skills, trust, and self-assessed empathy along with the
      perceptions of students regarding their training experiences. METHOD: Medical
      students underwent simulation-based end-of-life care OSCE training that involved
      standardized patients who evaluated students' communication skills and physician
      trust with the Kalamazoo Essential Elements Communication Checklist and the Wake
      Forest Physician Trust Scale. Students also completed the Jefferson Scale of
      Physician Empathy. Pearson correlation was used to examine the relationship
      between OSCE performance grades and communication, trust, and empathy scores.
      Student comments were analyzed using the constant comparative method of analysis
      to identify dominant themes. RESULTS: The 389 students (mean age 26.6 +/- 2.8 y;
      54.5% female) had OSCE grades that were positively correlated with physician
      trust scores (r = 0.325, P < 0.01) and communication skills (r = 0.383, P <
      0.01). However, OSCE grades and self-reported empathy were not related (r =
      0.021, P = 0.68). Time of clerkship differed for OSCE grade and physician trust
      scores; however, there was no trend identified. No differences were noted between
      the time of clerkship and communication skills or empathy. Overall, students
      perceived simulation-based end-of-life care training to be a valuable learning
      experience and appreciated its placement early in clinical training. CONCLUSIONS:
      We found that simulation-based OSCE training in palliative and end-of-life care
      can be effectively conducted during a surgery clerkship. Moreover, the
      standardized patient encounters combined with the formal assessment of
      communication skills, physician trust, and empathy provide feedback to students
      at an early phase of their professional life. The positive and appreciative
      comments of students regarding the opportunity to practice difficult patient
      conversations suggest that attention to these professional characteristics and
      skills is a valued element of clinical training and conceivably a step toward
      better patient outcomes and satisfaction.

PMID- 25858545
TI  - Understanding cardiogenic shock.

PMID- 25858546
TI  - Relationship between testosterone, estradiol and circulating PCSK9: Cross
      sectional and interventional studies in humans.
AB  - BACKGROUND: Circulating PCSK9 levels are higher in women than men, in
      postmenopausal than premenopausal women, and in pregnant than non-pregnant women,
      suggesting that sex hormones may be related to PCSK9 levels. We have examined the
      relationship between serum estradiol (E2) and testosterone (T) and PCSK9, and the
      impact of E2 replacement therapy in women and T replacement and ablation therapy
      in men on circulating PCSK9. METHODS: We conducted a cross-sectional study to
      examine the correlation between serum T (in males) and E2 (in females) and serum
      PCSK9. We also conducted interventional studies to examine the effect of hormonal
      therapy on serum PCSK9 levels. RESULTS: In men, (1) serum T does not correlate
      with circulating PCSK9 or with LDLC in the basal state, (2) T replacement therapy
      does not have any effect on circulating PCSK9, and (3) T ablation therapy has
      mixed results. In women, (1) E2 correlates inversely with circulating PCSK9 and
      directly with serum LDLC, but (2) E2 replacement therapy does not have any effect
      on circulating PCSK9. CONCLUSIONS: We demonstrate differences between men and
      women in the relationship of their major sex hormones with circulating PCSK9. In
      men, circulating PCSK9 is not related to or affected by T except for a possible
      effect during T ablation therapy. In women, E2 is inversely related to
      circulating PCSK9 but the lack of effect of E2 therapy on circulating PCSK9
      suggests that the E2-related differences in PCSK9 levels may be the result of
      differences in receptor-mediated PCSK9 clearance through E2-induced changes
      rather than production of PCSK9. The studies were registered with
      ClinicalTrials.gov NCT00848276.

PMID- 25858547
TI  - Apolipoprotein M.
AB  - Apolipoprotein M (ApoM) is a novel apolipoprotein that was discovered in 1999 and
      is bound primarily to high-density lipoproteins (HDLs) in the plasma. Multiple
      factors may influence its expression at both the post-transcriptional and the
      transcriptional levels both in vivo and ex vivo as follows: hepatocyte nuclear
      factor-1alpha, 4alpha (HNF-1alpha, 4alpha), liver receptor homolog-1 (LRH-1),
      forkhead box A2 (Foxa2) and platelet activating factor (PAF) upregulate its
      expression; liver X receptor (LXR), retinoid X receptor (RXR), farnesoid X
      receptor (FXR), small heterodimer partner (SHP) and the majority of cytokines
      downregulate its expression. However, mechanisms underlying these processes
      remain unknown. Structurally, there exists a characterized hydrophobic binding
      pocket within the apoM protein, which enables it to bind functional lipids such
      as Sphingosine-1-Phosphate (S1P). Functionally, it facilitates the formation of
      prebeta-HDL and enhances an avalanche of atheroprotective effects exerted by HDL.
      Moreover, in patients with diabetes, the levels of plasma apoM may decrease,
      whereas the augmentation of apoM decreases plasma glucose levels and magnifies
      the secretion of insulin. This article offers a panorama of the progress made in
      the research regarding the characteristics of apoM, particularly the regulation
      of its expression and its functions. 

PMID- 25858548
TI  - CSF3R and CALR mutations in paediatric myeloid disorders and the association of
      CSF3R mutations with translocations, including t(8; 21).
AB  - Mutations in the colony-stimulating factor 3 receptor (CSF3R) and calreticulin
      (CALR) genes have been reported in a proportion of adults with myeloproliferative
      disease. However, little is known about CSF3R or CALR mutations in paediatric
      myeloid disorders. We analysed CSF3R exons 14 and 17, and CALR exon 9, using
      direct sequencing in samples of paediatric acute myeloid leukaemia (AML; n =
      521), juvenile myelomonocytic leukaemia (JMML; n = 40), myelodysplastic syndrome
      (MDS; n = 20) and essential thrombocythaemia (ET; n = 21). CSF3R mutations were
      found in 10 (1.2%) of 521 patients with AML; two in exon 14 (both missense
      mutations resulting in p.T618I) and eight in exon 17 (three frameshift mutations:
      p.S715X, p.Q774R, and p.S783Q; and five novel missense mutations: p.Q754K,
      p.R769H, p.L777F, p.T781I, and S795R). All of the patients with mutations in
      CSF3R exon 17 had chromosomal translocations, including four with t(8;21). At the
      time of reporting, seven of these ten patients are alive; three have died, due to
      side effects of chemotherapy. No CSF3R mutations were found in cases of MDS, JMML
      or ET. The only mutation found in the CALR gene was a frameshift (p.L367 fs) in
      one ET patient. We discuss the potential impact of these findings for the
      leukaemogenesis and clinical features of paediatric myeloid disorders.

PMID- 25858549
TI  - Clonality and antimicrobial susceptibility of methicillin-resistant
      Staphylococcus aureus at the University Hospital Zurich, Switzerland between 2012
      and 2014.
AB  - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a global
      epidemic threat. The aim of this study was to determine which globally known MRSA
      lineages are currently present at our tertiary care hospital in Switzerland, a
      hospital with low MRSA prevalence. In light of the increasing prevalence of multi
      drug resistance including vancomycin resistance we also assessed antibiotic
      susceptibilities. METHODS: The 146 MRSA strains collected over two years (March
      2012 until February 2014) at the University Hospital Zurich, Switzerland, were
      analyzed by PFGE analysis of SmaI digests in combination with spa-typing. In
      addition, representative isolates were analyzed by multi locus sequence typing
      (MLST). Susceptibilities to eight antibiotics were assessed using the Kirby-Bauer
      disc diffusion method. RESULTS: Isolates showed resistance to erythromycin (48%),
      ciprofloxacin (43%), clindamycin (31%), tetracycline (22%), and gentamicin (16%).
      All isolates were susceptible to vancomycin, 95% were susceptible to
      sulfamethoxazole/trimethoprim and rifampicin, respectively. PFGE analysis
      revealed 22 different patterns, with four major patterns that accounted for 53.4%
      of all MRSA isolates, and seven sporadic patterns. Spa typing revealed 50
      different spa types with the predominant types being t008 (14%), t002 (10%), and
      t127 (9%). 82% of the MRSA isolates could be assigned to six clonal complexes
      (CCs) namely CC1 (10%), CC5 (23%), CC8 (18%), CC22 (17%), CC30 (11%), and CC45
      (3%) based on spa-types, PFGE patterns, and MLST. Two isolates could not be typed
      by either PFGE analysis or spa-typing and three isolates had spa-types that have
      not yet been described. CONCLUSIONS: The combination of the two typing methods
      was more discriminatory as compared to the use of a single method. Several of the
      lineages that are predominant in Europe are present in our hospital. Resistances
      to antibiotics have decreased in comparison to a study conducted between 2004 and
      2006.

PMID- 25858550
TI  - Latent transforming growth factor-beta binding proteins (LTBP-1 and LTBP-2) and
      gingiva keratinization.
AB  - OBJECTIVE: Transforming growth factor-beta (TGF-beta) proteins are involved in
      epithelial keratinization. The major function of latent TGF-beta binding proteins
      (LTBPs) is modulating TGF-beta activity. However, whether LTBP-1 and LTBP-2 play
      roles in gingiva keratinization remains unclear. MATERIALS AND METHODS: Human
      keratinized gingiva and non-keratinized alveolar mucosa were processed for LTBP
      1, LTBP-2, cytokeratin-1 (K1), cytokeratin-4 (K4), and TGF-beta
      immunohistochemical (IHC) staining. Porcine heterotopically transplanted
      connective tissues and newly grown epithelia were harvested for IHC staining. The
      expression levels of LTBP-1 and LTBP-2 were compared between differentiated and
      undifferentiated human normal oral keratinocytes (hNOK). The expression of LTBP-1
      and LTBP-2 was knocked down in a cell line (OEC-M1) to evaluate the effects on
      the expression of K1, K4, and involucrin (INV). RESULTS: In human and porcine
      specimens, LTBP-2 expression patterns distinguished keratinized and non
      keratinized oral epithelia. Western blotting results showed that K1, LTBP-1, and
      INV proteins were upregulated in differentiated hNOK. In OEC-M1 cells, LTBP-2
      knockdown resulted in upregulated the expression of K1 and INV and downregulated
      the expression of K4. LTBP-1 knockdown resulted in opposite effects. CONCLUSION:
      The expression patterns of LTBP-2 differ in keratinized gingiva and non
      keratinized mucosa. LTBP-1 and LTBP-2 are involved in the keratinization of oral
      epithelium; however, the underlying mechanism remains to be elucidated.

PMID- 25858552
TI  - Response of Dictyostelium discoideum to UV-C and involvement of poly (ADP-ribose)
      polymerase.
AB  - OBJECTIVES: Radiation and chemical mutagens are direct DNA-damaging agents and
      ultraviolet (UV) radiation is frequently used in biological studies. Consequent
      to ozone depletion, UV-C could become a great challenge to living organisms on
      earth, in the near future. The present study has focused on the role of poly (ADP
      ribose) polymerase (PARP) during UV-C-induced growth and developmental changes in
      Dictyostelium discoideum, a phylogenetically important unicellular eukaryote.
      MATERIALS AND METHODS: Dictyostelium discoideum cells were exposed to different
      doses of UV-C and PARP activity, and effects of its inhibition were studied.
      Expression of developmentally regulated genes yakA, car1, aca, csA, regA, ctnA,
      ctnB, gp24, hspD and dsn were analysed using semiquantitative RT-PCR. RESULTS: We
      report that the D. discoideum cells displayed PARP activation within 2 min of UV
      C irradiation and there was increase in NO levels in a dose-dependent manner. UV
      C-irradiated cells had impaired growth, delayed or blocked development and
      delayed germination compared to control cells. In our previous studies we have
      shown that inhibition of PARP recovered oxidative stress-induced changes in D.
      discoideum; however, intriguingly PARP inhibition did not correct all defects as
      effectively in UV-C-irradiated cells. This possibly was due to interplay with
      increased NO signalling. CONCLUSIONS: Our results signify that UV-C and oxidative
      stress affected growth and development in D. discoideum by different mechanisms;
      these studies could provide major clues to complex mechanisms of growth and
      development in higher organisms.

PMID- 25858553
TI  - Epidemiology of Clostridium difficile infection: results of a hospital-based
      study in Krakow, Poland.
AB  - Over the past two decades Clostridium difficile infection (CDI) has appeared as a
      major public health threat. We performed a retrospective study based on the
      records of patients hospitalized for CDI at the University Hospital in Krakow,
      Poland, between 2008 and 2014. In the study period, CDI occurred in 1009
      individuals. There were 790 (78%) individuals who developed infection only once,
      whereas 219 (22%) developed infection more than once. The percentage of deaths
      within 14 days of CDI confirmation was 2.4%, with a mean age of 74.2 +/- 15.9
      years. Crude mortality was 12.9% in medical wards, 5.6% for surgical wards and
      27.7% in the ICU setting. The time span between diagnosis and death was 5.1 days
      on average. Between 2008 and 2012 a 6.5-fold increase of CDI frequency with a
      posterior stabilization and even reduction in 2013 and 2014 was observed.
      According to the data analysed, 2/3 patients in our population developed CDI
      during their hospitalization even though they were admitted for different
      reasons. Medical wards pose a significantly higher risk of CDI than the surgical
      ones. Age is a risk factor for CDI recurrence. In the case of patients who died,
      death occurred shortly after diagnosis. The first CDI episode poses much higher
      risk of mortality than the consecutive ones. 

PMID- 25858551
TI  - Early-life house dust mite allergens, childhood mite sensitization, and
      respiratory outcomes.
AB  - BACKGROUND: Exposure to indoor allergens during early life may play a role in the
      development of the immune system and inception of asthma. OBJECTIVE: To describe
      the house dust mite (HDM) allergen concentrations in bedroom dust during early
      life and to evaluate its associations with HDM sensitization, wheezing, and
      asthma, from birth to school age, in 5 geographically spread European birth
      cohorts. METHODS: We included 4334 children from INMA-Menorca (Spain), BAMSE
      (Sweden), LISAplus and MAS (Germany), and PIAMA-NHS (the Netherlands). Dust
      samples were collected from bedrooms during early life and analyzed for
      Dermatophagoides pteronyssinus (Der p1) and Dermatophagoides farinae (Der f1).
      HDM concentrations were divided into four categories. Sensitization was
      determined by specific IgE. Wheezing and asthma information up to 8/10 years was
      collected through questionnaires. We performed mixed-effects logistic regression
      models and expressed associations as odds ratios with 95% confidence intervals.
      RESULTS: House dust mite concentrations varied across cohorts. Mean allergen
      concentrations were highest in INMA-Menorca (geometric mean (GM) Der p1 = 3.3
      MUg/g) and LISAplus (GM Der f1 = 2.1 MUg/g) and lowest in BAMSE (GM Der p1 = 0.1
      MUg/g, Der f1 = 0.3 MUg/g). Moderate and high HDM concentrations were
      significantly (P-values < 0.05) associated with 50-90% higher prevalence of HDM
      sensitization. No significant associations were observed with respiratory
      outcomes. CONCLUSION: Our study based on geographically spread regions, a large
      sample size, and a wide range of allergen concentration shows that HDM allergen
      concentrations vary across regions and that exposure during early life plays a
      role in the development of allergic sensitization but not in the development of
      respiratory outcomes.

PMID- 25858554
TI  - Fabrication of charged membranes by the solvent-assisted lipid bilayer (SALB)
      formation method on SiO2 and Al2O3.
AB  - In this study, we employed the solvent-assisted lipid bilayer (SALB) formation
      method to fabricate charged membranes on solid supports. The SALB formation
      method exploits a ternary mixture of lipid-alcohol-aqueous buffer to deposit
      lamellar phase structures on solid supports upon gradual increase of the buffer
      fraction. Using the quartz crystal microbalance with dissipation (QCM-D)
      technique, we investigated the formation of negatively and positively charged
      membranes via the SALB formation method and directly compared with the vesicle
      fusion method on two different oxide films. Bilayers containing an increasing
      fraction of negatively charged DOPS lipid molecules were successfully formed on
      both SiO2 and Al2O3 substrates using the SALB formation method at physiological
      pH (7.5). In contrast, the vesicle fusion method did not support bilayer
      formation on Al2O3 and those containing more than 10% DOPS ruptured on SiO2 only
      under acidic conditions (pH 5). Characterization of the fraction of negatively
      charge DOPS by in situ annexin 5A binding assay revealed that the fraction of
      DOPS lipid molecules in the bilayers formed on Al2O3 is significantly higher than
      that formed on SiO2. This suggests that the SALB self-assembly of charged
      membranes is predominantly governed by the electrostatic interaction.
      Furthermore, our findings indicate that when multicomponent lipid mixtures are
      used, the relative fraction of lipids in the bilayer may differ from the fraction
      of lipids in the precursor mixture. 

PMID- 25858555
TI  - Current Concepts of the Carpal Boss: Pathophysiology, Symptoms, Clinical or
      Imaging Diagnosis, and Management.
AB  - The carpal boss reflects an osseous protuberance at the level of the dorsal base
      of the second or third metacarpal, variably present in the general population.
      There are numerous theories as to the etiology of the bony excrescence; however,
      the exact cause remains uncertain. The abnormality can result in dorsal wrist
      pain and swelling. The diagnosis is typically established based on clinical
      examination and imaging, including radiography, ultrasound, nuclear medicine,
      computed tomography, and magnetic resonance imaging. We review the proposed
      theories of how the carpal boss develops, explain the clinical manifestations,
      demonstrate the imaging appearance, and address treatment strategies. 

PMID- 25858556
TI  - Nephrogenic Systemic Fibrosis on Mammography.
AB  - Nephrogenic systemic fibrosis, previously known as nephrogenic fibrosing
      dermopathy, is a multiorgan sclerotic disorder that is strongly linked to the
      administration of gadolinium-based chelates used for intravenous contrast in
      magnetic resonance imaging procedures. Although involvement of truncal skin is a
      relatively common, few reports of its appearance on mammography exist in the
      literature. 

PMID- 25858558
TI  - Three new, early diverging Carex (Cariceae, Cyperaceae) lineages from East and
      Southeast Asia with important evolutionary and biogeographic implications.
AB  - Traditional Cariceae and Carex (1966 spp.) classifications recognised five genera
      (Carex, Cymophyllus, Kobresia, Schoenoxiphium, Uncinia) and four subgenera
      (Carex, Vignea, Vigneastra, Psyllophora). However, molecular studies have shown
      that only Carex, divided into five major lineages (the Core Carex,
      Schoenoxiphium, Core Unispicate, Vignea and Siderostictae Clades), is natural.
      These studies have also suggested that many early diverging tribal lineages are
      East Asian in origin, but the sampling of East Asian groups has been poor, and
      support for relationships within and among major Cariceae clades has been weak.
      To test deep patterns of relationship in Carex we assembled the longest sequence
      dataset yet (ITS, ETS 1f, matK, ndhF, rps16; ca. 4400bp) with taxonomic sampling
      focused on critical East and Southeast Asian Carex sections that have blurred
      subgeneric limits (Decorae, Graciles, Mundae) or have been at the heart of
      theories on tribal origins (Hemiscaposae, Indicae, Surculosae, Euprepes,
      Mapaniifoliae, Hypolytroides). Results indicate that subg. Vigneastra is highly
      polyphyletic (in five of seven major lineages recognised), and they provide the
      strongest support yet seen for all previously recognised major Cariceae clades in
      a single analysis (?93% BS). Moreover, results provide strong evidence for three
      previously unrecognised early diverging East and Southeast Asian lineages: a
      "Hypolytroides Clade" (sect. Hypolytroides) sister to the Siderostictae Clade,
      and for a "Dissitiflora Lineage" (sect. Mundae) and a morphologically diverse
      "Small Core Carex Clade" (sects. Graciles, Decorae, Mapaniifoliae, Euprepes,
      Indicae) as successive sisters to approximately 1400 species in the Core Carex
      Clade. Our findings also suggest that morphological diversification may have
      occurred in clades dominated by Asian species followed by canalization to a
      narrower range of morphologies in species-rich, cosmopolitan lineages. 

PMID- 25858557
TI  - Silk scaffolds with tunable mechanical capability for cell differentiation.
AB  - Bombyx mori silk fibroin is a promising biomaterial for tissue regeneration and
      is usually considered an "inert" material with respect to actively regulating
      cell differentiation due to few specific cell signaling peptide domains in the
      primary sequence and the generally stiffer mechanical properties due to
      crystalline content formed in processing. In the present study, silk fibroin
      porous 3D scaffolds with nanostructures and tunable stiffness were generated via
      a silk fibroin nanofiber-assisted lyophilization process. The silk fibroin
      nanofibers with high beta-sheet content were added into the silk fibroin
      solutions to modulate the self-assembly, and to directly induce water-insoluble
      scaffold formation after lyophilization. Unlike previously reported silk fibroin
      scaffold formation processes, these new scaffolds had lower overall beta-sheet
      content and softer mechanical properties for improved cell compatibility. The
      scaffold stiffness could be further tuned to match soft tissue mechanical
      properties, which resulted in different differentiation outcomes with rat bone
      marrow-derived mesenchymal stem cells toward myogenic and endothelial cells,
      respectively. Therefore, these silk fibroin scaffolds regulate cell
      differentiation outcomes due to their mechanical features.

PMID- 25858559
TI  - The evolutionary history of the embiotocid surfperch radiation based on genome
      wide RAD sequence data.
AB  - The radiation of surfperches (Embiotocidae) in the temperate North Pacific has
      been suggested to be the product of ecological competition and niche
      partitioning. Surfperches are a family of viviparous marine fishes, which have
      been used to study multiple paternity, sperm competition, and population
      genetics. Phylogenetic inference is essential for interpreting the evolutionary
      context of embiotocid life history traits and testing alternative scenarios, yet
      previous studies have yielded phylogenies with low support and incongruent
      topologies. Here we constructed reduced representation genomic libraries using
      restriction-site associated DNA (RAD) sequence markers to infer phylogenetic
      relationships among all genera and 22 out of 24 embiotocid species. Orthologous
      markers retained across 91% of sampled species, corresponding to 523 loci,
      yielded trees with the highest support values. Our results support a scenario
      where embiotocids first diverged into clades associated with sandy and reef
      habitats during the middle Miocene (13-18Mya) with subsequent invasions of novel
      habitats in the reef associated clade, and northern range expansion in the
      Northwest Pacific. The appearance of California kelp forests (Laminariales) in
      the late Miocene (8-15Mya) correlates with further proliferation in the reef
      associated clade. In all cases, radiations occurred within specific habitats, a
      pattern consistent with niche partitioning. We infer fine scale species
      relationships among surfperches with confidence and corroborate the utility of
      RAD data for phylogenetic inference in young lineages. 

PMID- 25858560
TI  - AMPK Suppresses Vascular Inflammation In Vivo by Inhibiting Signal Transducer and
      Activator of Transcription-1.
AB  - Activation of AMPK suppresses inflammation, but the underlying mechanisms remain
      poorly understood. This study was designed to characterize the molecular
      mechanisms by which AMPK suppresses vascular inflammation. In cultured human
      aortic smooth muscle cells, pharmacologic or genetic activation of AMPK inhibited
      the signal transducer and activator of transcription-1 (STAT1), while inhibition
      of AMPK had opposite effects. Deletion of AMPKalpha1 or AMPKalpha2 resulted in
      activation of STAT1 and in increases in proinflammatory mediators, both of which
      were attenuated by administration of STAT1 small interfering RNA or fludarabine,
      a selective STAT1 inhibitor. Moreover, AMPK activation attenuated the
      proinflammatory actions induced by STAT1 activators such as interferon-gamma and
      angiotensin II (AngII). Mechanistically, we found that AMPK activation increased,
      whereas AMPK inhibition decreased, the levels of mitogen-activated protein kinase
      phosphatase-1 (MKP-1), an inducible nuclear phosphatase, by regulating proteasome
      dependent degradation of MKP-1. Gene silencing of MKP-1 increased STAT1
      phosphorylation and prevented 5-aminoimidazole-4-carboxyamide ribonucleoside
      reduced STAT1 phosphorylation. Finally, we found that infusion of AngII caused a
      more severe inflammatory response in AMPKalpha2 knockout mouse aortas, all of
      which were suppressed by chronic administration of fludarabine. We conclude that
      AMPK activation suppresses STAT1 signaling and inhibits vascular inflammation
      through the upregulation of MKP-1. 

PMID- 25858561
TI  - Enhancing Cardiac Triacylglycerol Metabolism Improves Recovery From Ischemic
      Stress.
AB  - Elevated cardiac triacylglycerol (TAG) content is traditionally equated with
      cardiolipotoxicity and suggested to be a culprit in cardiac dysfunction. However,
      previous work demonstrated that myosin heavy-chain-mediated cardiac-specific
      overexpression of diacylglycerol transferase 1 (MHC-DGAT1), the primary enzyme
      for TAG synthesis, preserved cardiac function in two lipotoxic mouse models
      despite maintaining high TAG content. Therefore, we examined whether increased
      cardiomyocyte TAG levels due to DGAT1 overexpression led to changes in cardiac
      TAG turnover rates under normoxia and ischemia-reperfusion conditions. MHC-DGAT1
      mice had elevated TAG content and synthesis rates, which did not alter cardiac
      function, substrate oxidation, or myocardial energetics. MHC-DGAT1 hearts had
      ischemia-induced lipolysis; however, when a physiologic mixture of long-chain
      fatty acids was provided, enhanced TAG turnover rates were associated with
      improved functional recovery from low-flow ischemia. Conversely, exogenous supply
      of palmitate during reperfusion suppressed elevated TAG turnover rates and
      impaired recovery from ischemia in MHC-DGAT1 hearts. Collectively, this study
      shows that elevated TAG content, accompanied by enhanced turnover, does not
      adversely affect cardiac function and, in fact, provides cardioprotection from
      ischemic stress. In addition, the results highlight the importance of exogenous
      supply of fatty acids when assessing cardiac lipid metabolism and its
      relationship with cardiac function. 

PMID- 25858562
TI  - GLP-1(32-36)amide Pentapeptide Increases Basal Energy Expenditure and Inhibits
      Weight Gain in Obese Mice.
AB  - The prevalence of obesity-related diabetes is increasing worldwide. Here we
      report the identification of a pentapeptide, GLP-1(32-36)amide (LVKGRamide),
      derived from the glucoincretin hormone GLP-1, that increases basal energy
      expenditure and curtails the development of obesity, insulin resistance,
      diabetes, and hepatic steatosis in diet-induced obese mice. The pentapeptide
      inhibited weight gain, reduced fat mass without change in energy intake, and
      increased basal energy expenditure independent of physical activity. Analyses of
      tissues from peptide-treated mice reveal increased expression of UCP-1 and UCP-3
      in brown adipose tissue and increased UCP-3 and inhibition of acetyl-CoA
      carboxylase in skeletal muscle, findings consistent with increased fatty acid
      oxidation and thermogenesis. In palmitate-treated C2C12 skeletal myotubes, GLP
      1(32-36)amide activated AMPK and inhibited acetyl-CoA carboxylase, suggesting
      activation of fat metabolism in response to energy depletion. By mass
      spectroscopy, the pentapeptide is rapidly formed from GLP-1(9-36)amide, the major
      form of GLP-1 in the circulation of mice. These findings suggest that the
      reported insulin-like actions of GLP-1 receptor agonists that occur independently
      of the GLP-1 receptor might be mediated by the pentapeptide, and the previously
      reported nonapeptide (FIAWLVKGRamide). We propose that by increasing basal energy
      expenditure, GLP-1(32-36)amide might be a useful treatment for human obesity and
      associated metabolic disorders. 

PMID- 25858563
TI  - Hypothalamic Neuropeptide 26RFa Acts as an Incretin to Regulate Glucose
      Homeostasis.
AB  - 26RFa is a hypothalamic neuropeptide that promotes food intake. 26RFa is
      upregulated in obese animal models, and its orexigenic activity is accentuated in
      rodents fed a high-fat diet, suggesting that this neuropeptide might play a role
      in the development and maintenance of the obese status. As obesity is frequently
      associated with type 2 diabetes, we investigated whether 26RFa may be involved in
      the regulation of glucose homeostasis. In the current study, we show a moderate
      positive correlation between plasma 26RFa levels and plasma insulin in patients
      with diabetes. Plasma 26RFa concentration also increases in response to an oral
      glucose tolerance test. In addition, we found that 26RFa and its receptor GPR103
      are present in human pancreatic beta-cells as well as in the gut. In mice, 26RFa
      attenuates the hyperglycemia induced by a glucose load, potentiates insulin
      sensitivity, and increases plasma insulin concentrations. Consistent with these
      data, 26RFa stimulates insulin production by MIN6 insulinoma cells. Finally, we
      show, using in vivo and in vitro approaches, that a glucose load induces a
      massive secretion of 26RFa by the small intestine. Altogether, the present data
      indicate that 26RFa acts as an incretin to regulate glucose homeostasis. 

PMID- 25858565
TI  - [Addictovigilance: the pharmacological challenge of assessment and prevention of
      risky substances].

PMID- 25858564
TI  - Platelet-dependent von Willebrand factor activity. Nomenclature and methodology:
      communication from the SSC of the ISTH.

PMID- 25858567
TI  - Signal identification in addictovigilance: the functioning of the French system.
AB  - The French addictovigilance network (addictovigilance: surveillance of
      addiction), composed of 13 Addictovigilance Centres, was set up in 1990 in order
      to achieve reliable surveillance and evaluation of abuse and dependence cases due
      to psychoactive substances (alcohol and tobacco excepted). The detection of
      safety signals is one of the roles of the addictovigilance centres. Signals from
      spontaneous reports need to be analyzed before further communication. In
      addictovigilance, signals may be linked to adverse effects (deaths, pathological
      signs), to products (new psychoactive substances with potentially dangerous
      effects) or to practices (new administration routes, new contexts of use). These
      signals are provided by numerous partners among whom the addictovigilance network
      has to raise awareness about information that may possibly be an alert signal.
      The watchful attitude of all partners will make it possible that signals will be,
      after analyze, considered as true alerts. The addictovigilance network collects
      data, assess the potential for addiction of psychoactive drugs to provide
      information on the risk of addiction and give opinions for public health
      decisions (harm reduction or prevention programs, psychoactive substances
      control, health alerts). 

PMID- 25858569
TI  - Addiction, experimental models and neurobiological mechanisms.
AB  - Humans have constantly sought to alleviate their existential anxieties, first
      resorting to substances found in their natural environment, and more recently,
      with the arrival of modern chemistry, using synthetic substances or medications.
      The substances used in this way are constantly renewing, warranting health
      surveillance and particular vigilance towards the addictive risk, given its major
      medical and social impact. This surveillance and vigilance requires detailed,
      accurate knowledge of the pharmacological and physio-pathological models involved
      in the emergence of the process of addiction, in particular disturbances of the
      systems regulating dopaminergic transfer; it also requires knowledge of the means
      to identify individual risk factors linked to genetic or psycho-behavioural
      susceptibilities. 

PMID- 25858571
TI  - Drug abuse monitoring: which pharmacoepidemiological resources at the European
      level?
AB  - Monitoring the potential for abuse and dependence of psychoactive substances
      falls within the scope of international conventions on narcotic drugs. At the
      European level, this monitoring is based on activities controlled by the European
      Monitoring Centre for Drugs and Drug Addiction (EMCDDA) for substance abuse in
      general and by the European Medicines Agency (EMA) for marketed drugs, in the
      context of pharmacovigilance. If France has set up in the early 1990s an original
      system to assess potential for abuse of psychoactive substances, with specific
      tools combining both the evaluation of the use of these substances (illicit
      substances or diverted drugs), and the consequences of that use in terms of
      morbidity and mortality, there is no equivalent in other European countries.
      Indeed, unlike the USA, who, for several decades, organized this type of
      surveillance, with a multisource approach (sentinel systems, databases, medical
      and administrative data, databases for seeking care in relation abuse), we have
      not found in other European countries integrated system for identifying a signal
      of drug abuse, or to assess the impact of measures for minimizing the risk of
      abuse. However, some recent examples show a growing concern about drug addiction,
      based on a pharmacoepidemiological approach using pharmacovigilance databases or
      medical administrative data. These examples illustrate the interest of these
      approaches in the field of drug of abuse. 

PMID- 25858573
TI  - New synthetic drugs in addictovigilance.
AB  - New substances, also known as "designer drugs" or "legal highs" are increasingly
      available to drug users. Two hundred and fifteen hitherto unlisted substances
      have been notified by European Union member states since 2005. These synthetic
      drugs, which have been developed to side-step the legislation on drugs, are
      analogues or derivatives of existing drugs and medications. The availability of
      these "legal highs", sold on Internet under various denominations such as bath
      salt, plant fertilizer, chemical not intended for human use, or spice, is
      unlimited. The effects felt by users vary, and the substances may be stimulant,
      entactogenic, hallucinogenic, psychedelic or dissociative. The pharmacological
      targets also vary, and may be either the increase of extracellular levels of
      neurotransmitters via different mechanisms (reuptake inhibition, stimulation of
      intracellular release) or else fixation on specific receptors. Several chemical
      classes, themselves divided into sub-classes, are involved: phenethylamines,
      tryptamines, piperazines, cathinones, cannabinoids etc. The toxicity of the main
      members of these categories is increasingly well known, the most deleterious
      being behavioural effects, physical manifestations, and cardiovascular
      consequences. However, small variations in their chemical structure can generate
      effects that are quantitatively different, thus enhancing their toxicity or
      addictive potential, and much remains to be achieved in terms of knowledge about
      these new drugs. These substances are indeed present on the French territory, as
      shown by data provided by the Observatoire Francais des Drogues et Toxicomanies,
      and notifications by the French Addictovigilance network. Screening in clinical
      toxicology laboratories is not widespread, since these molecules are not detected
      by the standard screening tests, so that there is probably an under-estimation of
      the use of these new drugs. The legislation on these substances changes
      regularly, with more and more countries classifying them as "narcotics" or
      illegal psychotropic drugs so as to restrict their use, applying a generic
      classification when possible.

PMID- 25858575
TI  - Example of an investigation of an "emergent" phenomenon in addiction vigilance:
      the case of methylphenidate.
AB  - Abuse of and addiction to medication are a major public health issue which is
      evolving fast, in particular in countries like France, one of the largest
      consumers of medication in Europe. As a single source of information is not
      generally sufficient to measure a phenomenon as difficult to apprehend as
      medication-related addiction, as can be seen in the case of methylphenidate, it
      is essential to mobilise all the tools available, here surveillance programmes
      developed by the French CEIP Addiction vigilance network, such as suspicious
      prescriptions indicating possible abuse data (OSIAP) or observatory of illegal or
      misused psychoactive medications (OPPIDUM), as well as the health insurance
      databases, and health professional sentinel networks. The latest data available
      on methylphenidate abuse in France suggests a stabilisation of the phenomenon,
      which emerged in the Provence-Alpes-Cote-d'Azur (PACA) region in southern France.
      It also evidences its diffusion to other regions, so that the information needs
      to be widely relayed, and suggests that health professionals should exercise the
      greatest caution in the use of this substance, and should look for early signs of
      its misuse. 

PMID- 25858577
TI  - Evaluation of abuse and dependence in addiction monitoring systems: tramadol as
      an example.
AB  - The objective of this paper is to present an evaluation of the potential for
      abuse of and dependence on a drug from the data obtained from the different
      pharmacoepidemiological tools used by the French network for evaluation and
      information on pharmacodependence and addiction monitoring taking the example of
      tramadol. Comparison of the data from spontaneous reports with surveys in
      specific populations and with evaluations of indicators of diverted uses does not
      highlight a major problem of tramadol abuse and dependence in terms of public
      health, but stresses the importance of paying attention to the signal. This
      example of addiction monitoring of tramadol illustrates the interest of comparing
      results obtained from different validated sources. The implementation of repeated
      observational programs of abuse of and dependence on psychoactive drugs is an
      important aid to health authorities to define the content of the information to
      be delivered or regulatory decisions to reduce these problematic uses. 

PMID- 25858579
TI  - New methadone formulation in France: results from 5 years of utilization.
AB  - BACKGROUND: In France, methadone has historically been less accessible than
      buprenorphine. In 2008, a dry formulation (capsule) was introduced into the
      market, aimed in particular to improve methadone accessibility. OBJECTIVE: To
      describe the impact (prevalence of use, patient profiles and compliance with
      requirements) of the dry methadone formulation in France. METHOD: A retrospective
      cohort (from 2008 to 2012) was created from the data of the French General Health
      Insurance System which covers 80% of the French population. For each years, all
      subjects affiliated to this insurance system in southeast France (about 8.5
      million inhabitants) with at least two reimbursements of methadone between 1st
      January and 31st December were selected. RESULTS: In 2012, the proportion of
      capsule users was almost the same as that of syrup users (40.0% versus 43.1%; p <
      0.001). The rise in the number of methadone users has followed the rise in
      capsule users. Over the study period, the proportion of patients using
      benzodiazepines or antidepressants was 6-9% (p < 0.001) higher for capsule users
      than for syrup users. On average over the study period, 18% of subjects had at
      least one concurrent issue of the two forms. CONCLUSION: The study has shown the
      rapid spread of the capsule formulation among methadone users. This may suggest
      that the capsule is well accepted by patients and the medical community. However,
      the monitoring of methadone-related deaths should continue because of the
      pharmacodynamic properties of methadone and the context of relaxed regulations
      concerning access to methadone maintenance treatement (MMT).

PMID- 25858580
TI  - What is the impact of genome-wide supported risk variants for schizophrenia and
      bipolar disorder on brain structure and function? A systematic review.
AB  - The powerful genome-wide association studies (GWAS) revealed common mutations
      that increase susceptibility for schizophrenia (SZ) and bipolar disorder (BD),
      but the vast majority were not known to be functional or associated with these
      illnesses. To help fill this gap, their impact on human brain structure and
      function has been examined. We systematically discuss this output to facilitate
      its timely integration in the psychosis research field; and encourage reflection
      for future research. Irrespective of imaging modality, studies addressing the
      effect of SZ/BD GWAS risk genes (ANK3, CACNA1C, MHC, TCF4, NRGN, DGKH, PBRM1,
      NCAN and ZNF804A) were included. Most GWAS risk variations were reported to
      affect neuroimaging phenotypes implicated in SZ/BD: white-matter integrity (ANK3
      and ZNF804A), volume (CACNA1C and ZNF804A) and density (ZNF804A); grey-matter
      (CACNA1C, NRGN, TCF4 and ZNF804A) and ventricular (TCF4) volume; cortical folding
      (NCAN) and thickness (ZNF804A); regional activation during executive tasks (ANK3,
      CACNA1C, DGKH, NRGN and ZNF804A) and functional connectivity during executive
      tasks (CACNA1C and ZNF804A), facial affect recognition (CACNA1C and ZNF804A) and
      theory-of-mind (ZNF804A); but inconsistencies and non-replications also exist.
      Further efforts such as standardizing reporting and exploring complementary
      designs, are warranted to test the reproducibility of these early findings. 

PMID- 25858581
TI  - Global mental health and neuroethics.
AB  - BACKGROUND: Global mental health is a relatively new field that has focused on
      disparities in mental health services across different settings, and on
      innovative ways to provide feasible, acceptable, and effective services in poorly
      resourced settings. Neuroethics, too, is a relatively new field, lying at the
      intersection of bioethics and neuroscience; it has studied the implications of
      neuroscientific findings for age-old questions in philosophy, as well as
      questions about the ethics of novel neuroscientific methods and interventions.
      DISCUSSION: In this essay, we address a number of issues that lie at the
      intersection of these two fields: an emphasis on a naturalist and empirical
      position, a concern with both disease and wellness, the importance of human
      rights in neuropsychiatric care, and the value of social inclusion and patient
      empowerment. SUMMARY: These different disciplines share a number of perspectives,
      and future dialogue between the two should be encouraged.

PMID- 25858582
TI  - Decitabine improves outcomes in older patients with acute myeloid leukemia and
      higher blast counts.

PMID- 25858583
TI  - Lack of genetic association of 5-HTR2A 102 T/C and -1438A/G polymorphisms with
      Tourette syndrome in a family-based association study in a Chinese Han
      population.
AB  - INTRODUCTION: Our purpose is to investigate whether polymorphisms of 102 T/C and 
      1438A/G in 5HTR2A are associated with Tourette syndrome (TS) in Chinese Han
      population. METHODS: A total of 178 TS trios were recruited in this study. After
      the allelic and genotypic distributions of two polymorphisms were genotyped using
      polymerase chain reaction and restriction fragment length polymorphism (PCR
      RFLP), we compared their genetic distributions with what is expected with Hardy
      Weinberg to explore whether there might be an association of these polymorphisms
      with TS by haplotype relative risk (HRR) and transmission disequilibrium test
      (TDT) statistics. RESULTS: Our results showed that no significant associations
      were found between the HTR2A 102 T/C and -1438A/G polymorphisms and TS (for HTR2A
      102 T/C: TDT = 2.041, df = 1, P = 0.175; HRR = 1.468, chi(2)  = 1.905, P = 0.168,
      95% confidence interval: 0.850-2.535; for HTR2A: -1438A/G, TDT = 0.093, df = 1, P
      = 0.819; HRR = 0.965, chi(2)  = 0.018, P = 0.894, 95% confidence interval: 0.574
      1.624). DISCUSSION: Our study suggested that the HTR2A 102T/C and -1438A/G
      polymorphisms may not be associated with susceptibility to TS, and thus do not
      play a major role in the development of TS in the Chinese Han population.
      However, these results need to be confirmed in a larger sample collected from
      different populations.

PMID- 25858584
TI  - Construction of dibenzo-fused seven- to nine-membered carbocycles via Bronsted
      acid-promoted intramolecular Friedel-Crafts-type alkenylation.
AB  - Bronsted acid-promoted intramolecular hydroarylation of alkynylbenzenes carrying
      an arylalkyl group at the ortho-position leads to
      alkylidenedibenzo[a,d]cycloheptenes, -octenes and -nonenes in up to quantitative
      yield with complete regioselectivity. The scope and limitation of this reaction
      and application to the synthesis of tricyclic antidepressants are described. 

PMID- 25858585
TI  - Free thyroxine concentrations by equilibrium dialysis and chemiluminescent
      immunoassays in 13 hypothyroid dogs positive for thyroglobulin antibody.
AB  - OBJECTIVE: To determine if concentrations of free thyroxine (FT4) measured by
      semi-automated chemiluminescent immunoassay (CLIA) correspond to FT4 determined
      by equilibrium dialysis (ED) in hypothyroid dogs positive for thyroglobulin
      antibody (TGA). ANIMALS: Thirteen TGA-positive dogs classified as hypothyroid
      based on subnormal FT4 concentrations by ED. METHODS: Qualitative assessment of
      canine TGA was performed using an enzyme-linked immunosorbent assay. Serum total
      thyroxine and total triiodothyronine concentrations were measured by
      radioimmunoassay. Serum FT4 concentration was determined by ED, and also by semi
      automated CLIA for human FT4 (FT4h) and veterinary FT4 (FT4v). Canine thyroid
      stimulating hormone concentration was measured by semi-automated CLIA. RESULTS:
      Each dog's comprehensive thyroid profile supported a diagnosis of hypothyroidism.
      For detection of hypothyroidism, sensitivities of CLIA for FT4h and FT4v were 62%
      (95% CI, 32-85%) and 75% (95% CI, 36-96%), respectively, compared to FT4 by ED.
      Five of 13 (38%) dogs had FT4h and 2 of 8 (25%) dogs had FT4v concentrations by
      CLIA that were increased or within the reference range. Percentage of false
      negative test results for FT4 by CLIA compared to ED was significantly (P < .0001
      for FT4h and P < .001for FT4v) higher than the hypothesized false-negative rate
      of 0%. CONCLUSIONS AND CLINICAL IMPORTANCE: Caution should be exercised in
      screening dogs for hypothyroidism using FT4 measured by CLIA alone. Some (25-38%)
      TGA-positive hypothyroid dogs had FT4 concentrations determined by CLIA that did
      not support a diagnosis of hypothyroidism.

PMID- 25858586
TI  - Beat it early: putative renoprotective haemodynamic effects of oral hypoglycaemic
      agents.
AB  - Diabetic kidney disease represents a considerable burden; around one-third of
      patients with type 2 diabetes develop chronic kidney disease. In health, the
      kidneys play an important role in the regulation of glucose homeostasis via
      glucose utilization, gluconeogenesis and glucose reabsorption. In patients with
      diabetes, renal glucose homeostasis is significantly altered with an increase in
      both gluconeogenesis and renal tubular reabsorption of glucose. Environmental
      factors, both metabolic (hyperglycaemia, obesity and dyslipidaemia) and
      haemodynamic, together with a genetic susceptibility, lead to the activation of
      pro-oxidative, pro-inflammatory and pro-fibrotic pathways resulting in kidney
      damage. Hyperfiltration and its haemodynamic-driven insult to the kidney
      glomeruli is an important player in proteinuria and progression of kidney disease
      towards end-stage renal failure. Control of glycaemia and blood pressure are the
      mainstays to prevent kidney damage and slow its progression. There is emerging
      evidence that some hypoglycaemic agents may have renoprotective effects which are
      independent of their glucose-lowering effects. Sodium-glucose co-transporter-2
      (SGLT-2) inhibitors may exert a renoprotective effect by a number of mechanisms
      including restoring the tubuloglomerular feedback mechanism and lowering
      glomerular hyperfiltration, reducing inflammatory and fibrotic markers induced by
      hyperglycaemia thus limiting renal damage. Simultaneous use of an SGLT-2
      inhibitor and blockade of the renin-angiotensin-aldosterone system may be a
      strategy to slow progression of diabetic nephropathy more than either drug alone.
      The use of dipeptidyl peptidase-4 inhibitors and glucagon-like peptide 1 receptor
      agonists may exert a renoprotective effect by reducing inflammation, fibrosis and
      blood pressure. Given the burden of diabetic kidney disease, any additional
      renoprotective benefit with hypoglycaemic therapy is to be welcomed. Large
      randomized controlled trials are currently underway investigating if these new
      anti-diabetic agents can provide renoprotection in diabetes.

PMID- 25858588
TI  - Structure of a Novel DNA-binding Domain of Helicase-like Transcription Factor
      (HLTF) and Its Functional Implication in DNA Damage Tolerance.
AB  - HLTF (helicase-like transcription factor) is a yeast RAD5 homolog found in
      mammals. HLTF has E3 ubiquitin ligase and DNA helicase activities, and plays a
      pivotal role in the template-switching pathway of DNA damage tolerance. HLTF has
      an N-terminal domain that has been designated the HIRAN (HIP116 and RAD5 N
      terminal) domain. The HIRAN domain has been hypothesized to play a role in DNA
      binding; however, the structural basis of, and functional evidence for, the HIRAN
      domain in DNA binding has remained unclear. Here we show for the first time the
      crystal structure of the HIRAN domain of human HLTF in complex with DNA. The
      HIRAN domain is composed of six beta-strands and two alpha-helices, forming an OB
      fold structure frequently found in ssDNA-binding proteins, including in
      replication factor A (RPA). Interestingly, this study reveals that the HIRAN
      domain interacts with not only with a single-stranded DNA but also with a duplex
      DNA. Furthermore, the structure unexpectedly clarifies that the HIRAN domain
      specifically recognizes the 3'-end of DNA. These results suggest that the HIRAN
      domain functions as a sensor to the 3'-end of the primer strand at the stalled
      replication fork and that the domain facilitates fork regression. HLTF is
      recruited to a damaged site through the HIRAN domain at the stalled replication
      fork. Furthermore, our results have implications for the mechanism of template
      switching. 

PMID- 25858587
TI  - Drosophila Low Temperature Viability Protein 1 (LTV1) Is Required for Ribosome
      Biogenesis and Cell Growth Downstream of Drosophila Myc (dMyc).
AB  - During animal development, various signaling pathways converge to regulate cell
      growth. In this study, we identified LTV1 as a novel cell growth regulator in
      Drosophila. LTV1 mutant larvae exhibited developmental delays and lethality at
      the second larval stage. Using biochemical studies, we discovered that LTV1
      interacted with ribosomal protein S3 and co-purified with free 40S ribosome
      subunits. We further demonstrated that LTV1 is crucial for ribosome biogenesis
      through 40S ribosome subunit synthesis and preribosomal RNA processing,
      suggesting that LTV1 is required for cell growth by regulating protein synthesis.
      We also demonstrated that Drosophila Myc (dMyc) directly regulates LTV1
      transcription and requires LTV1 to stimulate ribosome biogenesis. Importantly,
      the loss of LTV1 blocked the cell growth and endoreplication induced by dMyc.
      Combined, these results suggest that LTV1 is a key downstream factor of dMyc
      induced cell growth by properly maintaining ribosome biogenesis. 

PMID- 25858589
TI  - Genetic determinants of chronic oxaliplatin-induced peripheral neurotoxicity: a
      genome-wide study replication and meta-analysis.
AB  - We aimed at validating the role of genetic variants identified by a recent genome
      wide association study (GWAS) as determinants of chronic oxaliplatin-induced
      peripheral neurotoxicity (OXAIPN). Eight polymorphisms (rs10486003, rs2338,
      rs843748, rs797519, rs4936453, rs12023000, rs17140129, and rs6924717) were
      genotyped in a total of 150 colorectal cancer patients of Caucasian origin
      receiving oxaliplatin-based chemotherapy. The severity grade of chronic OXAIPN
      was assessed by NCI-CTC criteria and the clinical version of the Total Neuropathy
      Score((c)) (TNSc((c)) ). None of the polymorphisms investigated was found
      associated with grade >= 2 chronic OXAIPN (NCI-CTC criteria), while a nominal
      association emerged for ACYP2 rs843748 when using the TNSc((c)) scale (dominant
      model: odds ratio [OR]: 0.27, 95% confidence interval [CI]: 0.10-0.75, P =
      0.008). In the combined analysis of this results with data of the two previously
      published studies which assessed chronic OXAIPN by NCI-CTC criteria, evidence
      suggestive of association with chronic OXAIPN (NCI-CTC criteria) was found for
      ACYP2 rs843748 (dominant model: OR: 2.40, 95%CI: 1.40-5.24, P = 0.027), which,
      however, did not remain significant after correction for multiple testing
      (threshold P-value <0.00625). These findings suggest a minor role of the single
      nucleotide polymorphisms (SNPs) investigated as genetic determinants of chronic
      OXAIPN. These results also highlight the importance of replication studies with
      meta-analysis for validation of GWAS findings. 

PMID- 25858590
TI  - Good, but Not Perfect: Parental Knowledge About Risk Factors for Skin Cancer and
      the Necessity of Sun Protection in Southern Germany.
AB  - The level of knowledge and awareness of skin cancer risks in parents of young
      children is largely unknown. The Erlangen Kindergarten study, which enrolled
      3,129 parents of 3- to 6-year-old children in southern Germany, addressed this.
      The population-based survey found an overall high level of knowledge about skin
      cancer risks and strong support for the necessity of sun protection but
      identified two areas (role of intermittent sun exposure, sun protection on cloudy
      summer days) offering a target for improvement in future public health campaigns.

PMID- 25858592
TI  - Chloroanisoles may explain mold odor and represent a major indoor environment
      problem in Sweden.
AB  - Indoor mold odor is associated with adverse health effects, but the microbial
      volatiles underlying mold odor are poorly described. Here, chloroanisoles were
      studied as potential key players, being formed by microbial metabolism of
      chlorophenols in wood preservatives. Using a three-stage approach, we (i)
      investigated the occurrence of chloroanisoles in buildings with indoor air
      quality problems, (ii) estimated their frequency in Sweden, and (iii) evaluated
      the toxicological risk of observed chloroanisole concentrations. Analyses of 499
      building materials revealed several chloroanisole congeners in various types of
      buildings from the 1950s to 1970s. Evaluation of Swedish records from this time
      period revealed three coinciding factors, namely an unprecedented nationwide
      building boom, national regulations promoting wood preservatives instead of
      moisture prevention, and use of chlorophenols in these preservatives.
      Chlorophenols were banned in 1978, yet analysis of 457 indoor air samples
      revealed several chloroanisole congeners, but at median air levels generally
      below 15 ng/m(3) . Our toxicological evaluation suggests that these
      concentrations are not detrimental to human health per se, but sufficiently high
      to cause malodor. Thereby, one may speculate that chloroanisoles in buildings
      contribute to adverse health effects by evoking odor which, enhanced by belief of
      the exposure being hazardous, induces stress-related and inflammatory symptoms. 

PMID- 25858591
TI  - Maternal undernutrition and cardiometabolic disease: a Latin American
      perspective.
AB  - The current epidemic of obesity and cardiometabolic diseases in developing
      countries is described as being driven by socioeconomic inequalities. These
      populations have a greater vulnerability to cardiometabolic diseases due to the
      discrepancy between the maternal undernutrition and its consequence, low-birth
      weight progeny, and the subsequent modern lifestyles which are associated with
      socioeconomic and environmental changes that modify dietary habits, discourage
      physical activity and encourage sedentary behaviors. Maternal undernutrition can
      generate epigenetic modifications, with potential long-term consequences.
      Throughout life, people are faced with the challenge of adapting to changes in
      their environment, such as excessive intake of high energy density foods and
      sedentary behavior. However, a mismatch between conditions experienced during
      fetal programming and current environmental conditions will make adaptation
      difficult for them, and will increase their susceptibility to obesity and
      cardiovascular diseases. It is important to conduct research in the Latin
      American context, in order to define the best strategies to prevent the epidemic
      of cardiometabolic diseases in the region. 

PMID- 25858593
TI  - In vivo optical microscopy of peripheral nerve myelination with polarization
      sensitive-optical coherence tomography.
AB  - Assessing nerve integrity and myelination after injury is necessary to provide
      insight for treatment strategies aimed at restoring neuromuscular function.
      Currently, this is largely done with electrical analysis, which lacks direct
      quantitative information. In vivo optical imaging with sufficient imaging depth
      and resolution could be used to assess the nerve microarchitecture. In this
      study, we examine the use of polarization sensitive-optical coherence tomography
      (PS-OCT) to quantitatively assess the sciatic nerve microenvironment through
      measurements of birefringence after applying a nerve crush injury in a rat model.
      Initial loss of function and subsequent recovery were demonstrated by calculating
      the sciatic function index (SFI). We found that the PS-OCT phase retardation
      slope, which is proportional to birefringence, increased monotonically with the
      SFI. Additionally, histomorphometric analysis of the myelin thickness and g-ratio
      shows that the PS-OCT slope is a good indicator of myelin health and recovery
      after injury. These results demonstrate that PS-OCT is capable of providing
      nondestructive and quantitative assessment of nerve health after injury and shows
      promise for continued use both clinically and experimentally in neuroscience.

PMID- 25858594
TI  - Effects of titanium dioxide nanoparticles coupled with diode laser on optical
      properties of in vitro normal and cancerous human lung tissues studied with
      optical coherence tomography and diffuse reflectance spectra.
AB  - The objective is to investigate the effects of two different sized (60 and 100
      nm) titanium dioxide (TiO2) nanoparticles (NPs) penetration and accumulation in
      in vitro human normal lung (NL) tissue, lung squamous cell carcinoma (LSCC)
      tissue, and 650-nm diode laser-pretreated tissue on their optical properties
      studied with optical coherence tomography monitoring and diffuse reflectance (DR)
      spectra measurement. As with TiO2 NPs penetrating into the tissues, the
      intensities of DR of the samples increase, and then the enhancements of DR and
      the attenuation coefficients of the tissues were quantitatively calculated. The
      results suggest that 650-nm diode laser pretreatment increased the amounts of
      TiO2 NPs penetration and accumulation in NL and LSCC tissues, and the tissue
      optical properties were significantly influenced by accumulation of TiO2 NPs.

PMID- 25858595
TI  - Kidney tumor staging using surface-enhanced Raman scattering.
AB  - The detection of kidney cancers at an early stage is critical for diagnosis and
      therapy. Surface-enhanced Raman scattering (SERS) is investigated for early
      detection of cancer cases from biopsy samples. The colloidal silver nanoparticles
      as the SERS-active nanostructures are directly mixed with homogenized tissue
      samples. The SERS spectra from the normal and abnormal tissue samples collected
      from 40 cancer patients, 28 of them at T1 stage and 12 of them at T2-T3 stages,
      are analyzed using principal component analysis combined linear discriminant
      analysis with leave-one-out cross-validation method. It is found that the
      diagnosis sensitivity, specificity, and total accuracy of the approach can be as
      high as 100%. The results suggest that SERS can be used as a potential technique
      for the identification of the different tumor stages.

PMID- 25858596
TI  - Biodegradable nanoneedles for localized delivery of nanoparticles in vivo:
      exploring the biointerface.
AB  - Nanoneedles display potential in mediating the delivery of drugs and biologicals,
      as well as intracellular sensing and single-cell stimulation, through direct
      access to the cell cytoplasm. Nanoneedles enable cytosolic delivery, negotiating
      the cell membrane and the endolysosomal system, thus overcoming these major
      obstacles to the efficacy of nanotherapeutics. The low toxicity and minimal
      invasiveness of nanoneedles have a potential for the sustained nonimmunogenic
      delivery of payloads in vivo, provided that the development of biocompatible
      nanoneedles with a simple deployment strategy is achieved. Here we present a
      mesoporous silicon nanoneedle array that achieves a tight interface with the
      cell, rapidly negotiating local biological barriers to grant temporary access to
      the cytosol with minimal impact on cell viability. The tightness of this
      interfacing enables both delivery of cell-impermeant quantum dots in vivo and
      live intracellular sensing of pH. Dissecting the biointerface over time
      elucidated the dynamics of cell association and nanoneedle biodegradation,
      showing rapid interfacing leading to cytosolic payload delivery within less than
      30 minutes in vitro. The rapid and simple application of nanoneedles in vivo to
      the surface of tissues with different architectures invariably resulted in the
      localized delivery of quantum dots to the superficial cells and their prolonged
      retention. This investigation provides an understanding of the dynamics of
      nanoneedles' biointerface and delivery, outlining a strategy for highly local
      intracellular delivery of nanoparticles and cell-impermeant payloads within live
      tissues. 

PMID- 25858597
TI  - Moyamoya disease in two patients with Noonan-like syndrome with loose anagen
      hair.
AB  - Moyamoya disease is a unique chronic cerebrovascular condition caused by
      progressive stenosis of the arteries around the circle of Willis with prominent
      arterial collateral circulation. Noonan-like syndrome with loose anagen hair
      (NSLH) is characterized by short stature, characteristic facial phenotype, darkly
      pigmented and hairless skin, mild psychomotor delay with attention deficit
      disorder, and easily pluckable, sparse, thin, slow growing hair. Mutations in
      SHOC2 have been reported to underlie NSLH. In this paper, we describe two
      individuals with NSLH who also have moyamoya disease and in whom heterozygous
      germline mutation in SHOC2 was found.

PMID- 25858598
TI  - Treatment of invasive fungal disease using anidulafungin alone or in combination
      for hematologic patients with concomitant hepatic or renal impairment.
AB  - BACKGROUND: Invasive fungal disease (IFD) treatment is challenging in hematologic
      patients due to drug interactions and toxicities that limit the use of the
      antifungal agents. AIMS: To analyze retrospectively in terms of safety and
      potential efficacy anidulafungin therapy, alone or in combination. METHODS: Our
      institutional guidelines recommended anidulafungin treatment in hematologic
      patients with suspected IFD and concomitant renal or liver impairment (to avoid
      drug interactions and preserve organ function). RESULTS: From 2008 to 2013, 24
      episodes of IFD occurring in 21 patients were classified as proven (4 cases),
      probable (15 cases) and possible (5 cases). Anidulafungin was administered alone
      (13%) or in combination (88%). Eight (33%) episodes were resolved, using
      monotherapy (1 out of 3, 33%) or a combined therapy (7 out of 21, 33%). Twelve
      cases (50%) were registered as failure (death due to IFD progression in 4
      patients, and treatment change due to lack of efficacy in 8), and 4 cases (17%)
      were not evaluable (death unrelated to the IFD). Anidulafungin was not withdrawn
      in any case due to toxicity. CONCLUSIONS: Anidulafungin therapy, alone or in
      combination, could be considered in hematologic patients with IFD and concomitant
      liver or renal impairment. Due to the low number of patients, we cannot draw any
      conclusion about efficacy.

PMID- 25858599
TI  - [Subcutaneous phaeohyphomycosis caused by Phaeoacremonium parasiticum].
AB  - BACKGROUND: From the available literature, it is demonstrated that dematiaceous
      fungal infections mostly affect immunosuppressed patients. These infections can
      occur in different forms, from subcutaneous infection to disseminated forms that
      may compromise the life of the patient. In many cases the infection is related to
      the inoculation of the microorganism by diverse traumatic mechanisms, which
      determines the course of the infection to be slower in some cases. CASE REPORT:
      We describe two cases of phaeohyphomycosis caused by Phaeoacremonium parasiticum:
      A cancer patient with subcutaneous lesions affecting the left hand and forearm,
      and a patient who presented with subcutaneous abscesses in the left leg.
      CONCLUSIONS: These cases confirm the presence of this type of fungus in Spain. In
      the second case a combination of amphotericin B lipid complex and posaconazole,
      together with several surgical resections, were necessary in order to overcome
      the infection.

PMID- 25858600
TI  - Bilingualism alters brain functional connectivity between "control" regions and
      "language" regions: Evidence from bimodal bilinguals.
AB  - Previous neuroimaging studies have revealed that bilingualism induces both
      structural and functional neuroplasticity in the dorsal anterior cingulate cortex
      (dACC) and the left caudate nucleus (LCN), both of which are associated with
      cognitive control. Since these "control" regions should work together with other
      language regions during language processing, we hypothesized that bilingualism
      may also alter the functional interaction between the dACC/LCN and language
      regions. Here we tested this hypothesis by exploring the functional connectivity
      (FC) in bimodal bilinguals and monolinguals using functional MRI when they either
      performed a picture naming task with spoken language or were in resting state. We
      found that for bimodal bilinguals who use spoken and sign languages, the FC of
      the dACC with regions involved in spoken language (e.g. the left superior
      temporal gyrus) was stronger in performing the task, but weaker in the resting
      state as compared to monolinguals. For the LCN, its intrinsic FC with sign
      language regions including the left inferior temporo-occipital part and right
      inferior and superior parietal lobules was increased in the bilinguals. These
      results demonstrate that bilingual experience may alter the brain functional
      interaction between "control" regions and "language" regions. For different
      control regions, the FC alters in different ways. The findings also deepen our
      understanding of the functional roles of the dACC and LCN in language processing.

PMID- 25858601
TI  - The impact of stress on feedback and error processing during behavioral
      adaptation.
AB  - Stress is known to influence learning in a complex fashion. The present study
      aimed to examine, in how far feedback-based behavioral adaptation and
      electrophysiological correlates of error and feedback processing during this
      process are altered after acute stress. To this end, a learning task involving
      conditions with contingent and non-contingent monetary feedback was applied to 40
      healthy young men (two groups of 20 each). The participants of one group were
      stressed using the socially evaluated cold pressor test. A second group of
      participants underwent a control procedure before the task was administered and
      brain activity was assessed by means of electroencephalography. The analysis
      focused on the feedback-related negativity (FRN) and the error-related negativity
      (ERN). Stressed participants did not differ from controls in learning
      performance. They showed, however, an elevated FRN amplitude difference between
      punishment and reward compared to controls. Moreover, stressed but not control
      participants' FRN amplitudes reflected feedback contingency after learning and
      thus an outcome prediction error. For response-locked potentials, no significant
      group differences were found. These results indicate that stress leads to a
      stronger recruitment of the so-called reward system in the processing of
      performance feedback during feedback-based behavioral adaptation. 

PMID- 25858602
TI  - Concepts within reach: Action performance predicts action language processing in
      stroke.
AB  - The relationship between the brain's conceptual or semantic and sensory-motor
      systems remains controversial. Here, we tested manual and conceptual abilities of
      41 chronic stroke patients in order to examine their relationship. Manual
      abilities were assed through a reaching task using an exoskeleton robot. Semantic
      abilities were assessed with implicit as well as explicit semantic tasks, for
      both verbs and nouns. The results show that that the degree of selective
      impairment for action word processing was predicted by the degree of impairment
      in reaching performance. Moreover, the implicit semantic measures showed a
      correlation with a global reaching parameter, while the explicit semantic
      similarity judgment task predicted performance in action initiation. These
      results suggest that action concepts are dynamically grounded through motoric
      simulations, and that more details are simulated for more explicit semantic
      tasks. This is evidence for a close and causal relationship between sensory-motor
      and conceptual systems of the brain. 

PMID- 25858603
TI  - A job interview in the MRI scanner: How does indirectness affect addressees and
      overhearers?
AB  - In using language, people not only exchange information, but also navigate their
      social world - for example, they can express themselves indirectly to avoid
      losing face. In this functional magnetic resonance imaging study, we investigated
      the neural correlates of interpreting face-saving indirect replies, in a
      situation where participants only overheard the replies as part of a conversation
      between two other people, as well as in a situation where the participants were
      directly addressed themselves. We created a fictional job interview context where
      indirect replies serve as a natural communicative strategy to attenuate one's
      shortcomings, and asked fMRI participants to either pose scripted questions and
      receive answers from three putative job candidates (addressee condition) or to
      listen to someone else interview the same candidates (overhearer condition). In
      both cases, the need to evaluate the candidate ensured that participants had an
      active interest in comprehending the replies. Relative to direct replies, face
      saving indirect replies increased activation in medial prefrontal cortex,
      bilateral temporo-parietal junction (TPJ), bilateral inferior frontal gyrus and
      bilateral middle temporal gyrus, in active overhearers and active addressees
      alike, with similar effect size, and comparable to findings obtained in an
      earlier passive listening study (Basnakova et al., 2014). In contrast,
      indirectness effects in bilateral anterior insula and pregenual ACC, two regions
      implicated in emotional salience and empathy, were reliably stronger in
      addressees than in active overhearers. Our findings indicate that understanding
      face-saving indirect language requires additional cognitive perspective-taking
      and other discourse-relevant cognitive processing, to a comparable extent in
      active overhearers and addressees. Furthermore, they indicate that face-saving
      indirect language draws upon affective systems more in addressees than in
      overhearers, presumably because the addressee is the one being managed by a face
      saving reply. In all, face-saving indirectness provides a window on the cognitive
      as well as affect-related neural systems involved in human communication. 

PMID- 25858604
TI  - [In Process Citation].

PMID- 25858605
TI  - [Mechanisms of action, pharmacology and interactions of dolutegravir].
AB  - Dolutegravir is a second-generation integrase strand transfer inhibitor (INSTI),
      whose potential and binding half-life in the integrase are far superior to those
      of raltegravir and elvitegravir, conferring it with unique characteristics in
      terms of its genetic barrier to resistance and activity against viruses with one
      or more mutations in the integrase. The pharmacokinetic properties of
      dolutegravir allow once-daily dosing (50 mg), with or without food, maintaining
      concentrations far above those effective against wild-type viruses. If integrase
      resistance mutations are present, the recommended dosing regimen is 50 mg/12 h.
      The distribution of dolutegravir in cerebrospinal fluid is good and effective
      concentrations are also reached in the male and female genital tracts.
      Dolutegravir is metabolized by UGT1A1 and, to a lesser extent, by CYP3A4, without
      being an inducer or inhibitor of the usual metabolic systems. It has a very low
      potential for drug interactions and can be administered in routine doses with
      most drugs. Dose adjustment is not required, even in patients with renal
      insufficiency or mild or moderate liver failure. Increasing the dose of
      dolutegravir (50 mg/12 h) is only recommended when administered with efavirenz,
      nevirapine, fosamprenavir/r, tipranavir/r, rifampicin, carbamazepine, phenytoin
      and phenobarbital. Coadministration of dolutegravir with etravirine is not
      recommended without a protease inhibitor or with Hypericum perforatum.
      Dolutegravir should be administered 2 h before or 6 h after antacids or products
      with polyvalent cations. Dolutegravir can reduce renal tubule secretion of
      substances excreted via OCT2, with a slight initial increase in creatinine, with
      no risk of renal toxicity. The drug can also increase metformin concentrations
      and consequently monitoring is recommended in case dose adjustment is required.
      In summary, dolutegravir has excellent pharmacokinetic and drug interaction
      profiles. 

PMID- 25858606
TI  - [Safety profile of dolutegravir].
AB  - Integrase inhibitors are the latest drug family to be added to the therapeutic
      arsenal against human immunodeficiency virus infection. Drugs in this family that
      do not require pharmacological boosting are characterized by a very good safety
      profile. The latest integrase inhibitor to be approved for use is dolutegravir.
      In clinical trials, dolutegravir has shown an excellent tolerability profile,
      both in antiretroviral-naive and previously treated patients. Discontinuation
      rates due to adverse effects were 2% and 3%, respectively. The most frequent
      adverse effects were nausea, headache, diarrhea and sleep disturbance. A severe
      hypersensitivity reaction has been reported in only one patient. In patients
      coinfected with hepatropic viruses, the safety profile is similar to that in
      patients without coinfection. The lipid profile of dolutegravir is similar to
      that of raltegravir and superior to those of Atripla(r) and darunavir/ritonavir.
      Dolutegravir induces an early, predictable and non-progressive increase in serum
      creatinine of around 10% of baseline values in treatment-naive patients and of
      14% in treatment-experienced patients. This increase is due to inhibition of
      tubular creatinine secretion through the OCT2 receptor and does not lead to a
      real decrease in estimated glomerular filtration rate with algorithms that
      include serum creatinine. The effect of the combination of dolutegravir plus
      Kivexa((r)) on biomarkers of bone remodeling is lower than that of Atripla((r)).
      Dolutegravir has an excellent tolerability profile with no current evidence of
      long-term adverse effects. Its use is accompanied by an early and non-progressive
      increase in serum creatinine due to OCT2 receptor inhibition. In combination with
      abacavir/lamivudine, dolutegravir has a lower impact than
      enofovir/emtricitabine/efavirenz on bone remodelling markers. 

PMID- 25858607
TI  - [Efficacy of dolutegravir in treatment-naive patients. The SPRING-1, SPRING-2,
      SINGLE and FLAMINGO trials].
AB  - The efficacy of dolutegravir (DTG) in treatment-naive patients has been analyzed
      in the SPRING 1 and 2, SINGLE and FLAMINGO trials, which compared dolutegravir
      with the agents currently recommended as the drugs of choice in clinical practice
      guidelines in treatment-naive patients: efavirenz, raltegravir and
      darunavir/ritonavir. These trials confirmed the superiority (SINGLE and FLAMINGO)
      or the non-inferiority (SPRING-2) of dolutegravir. More than 2,000 patients were
      included in these 4 studies, lending value to their results and reinforcing the
      view of dolutegravir as the drug of choice in treatment-naive patients,
      accompanied either by abacavir/lamivudine (Kivexa((r))) or
      tenofovir/emtricitabine (Truvada(r)).

PMID- 25858608
TI  - [Resistance profile and genetic barrier of dolutegravir].
AB  - The resistance profile of dolutegravir differs significantly from those of
      earlier integrase inhibitors (INI). Dolutegravir displays in vitro activity
      against mutant HIV-1 harboring any isolated resistance mutations selected during
      failures to raltegravir or elvitegravir (Y143C/H/, N155H, Q148H/K/R, E92G/Q,
      T66A/I/K, T97A, E138A/K, G140A/S). Its activity is only compromised by Q148X
      mutations combined with other mutations, particularly > 1 mutation. The drug has
      pharmacokinetic/pharmacodynamic properties (plasmatic t1/2 15.3 h, inhibitory
      quotient 19, dissociative t1/2 from the IN-DNA complex 71 h) that favor a high
      genetic barrier to resistance. In vitro the selection of HIV-1 resistance to
      dolutegravir is extremely difficult to achieve. The mutations eventually selected
      (R263K, H51Y and E138K) do not confer significant resistance, and induce a
      fitness cost that prevents HIV-1 from evading drug pressure. Suprisingly, HIV-1
      is not able to compensate, leading the virus to a previously unnoticed
      evolutionary pathway with very low chances of developing resistance to INI or the
      backbone. No treatment-naive patients starting dolutegravir therapy (+TDF/FTC o
      ABC/3TC) have selected resistance in IN or against the backbone. No INI- naive
      patients with prior virologic failure selected phenotypic dolutegravir
      resistance. Only 4 out of 354 patients selected resistance mutations in IN, and
      rates of selection of mutations in IN or against the backbone were significantly
      lower than with raltegravir. In multitreated patients with widespread resistance
      including IN resistance, the high efficacy of dolutegravir was confirmed,
      irrespective of the previous pattern of IN mutations, provided that Q148X
      associated with other mutations was absent. 

PMID- 25858609
TI  - [Efficacy of dolutegravir in treatment-experienced patients: the SAILING and
      VIKING trials].
AB  - Dolutegravir is an HIV integrase inhibitor with a high genetic barrier to
      resistance and is active against raltegravir- and/or elvitegravir-resistant
      strains. The clinical development of dolutegravir for HIV infection rescue
      therapy is based on 3 clinical trials. In the SAILING trial, dolutegravir (5 mg
      once daily) in combination with 2 other antiretroviral agents was well tolerated
      and showed greater virological effect than raltegravir (400 mg twice daily) in
      the treatment of integrase inhibitor-naive adults with virological failure
      infected with HIV strains with at least two-class drug resistance. The VIKING
      studies were designed to evaluate the efficacy of dolutegravir as rescue therapy
      in treatment-experienced patients infected with HIV strains with resistance
      mutations to raltegravir and/or elvitegravir. VIKING-1-2 was a dose-ranging phase
      IIb trial. VIKING-3 was a phase III trial in which dolutegravir (50 mg twice
      daily) formed part of an optimized regimen and proved safe and effective in this
      difficult-to-treat group of patients. Dolutegravir is the integrase inhibitor of
      choice for rescue therapy in multiresistant HIV infection, both in integrase
      inhibitor-naive patients and in those previously treated with raltegravir or
      elvitegravir. 

PMID- 25858610
TI  - [Position of dolutegravir in the treatment of HIV infection].
AB  - Initial treatment with dolutegravir offers higher efficacy than treatment with
      efavirenz, darunavir/ritonavir and even with raltegravir in patients with a high
      viral load. Like ritonavir-boosted protease inhibitors, dolutegravir will
      probably have a high genetic barrier to resistance and prior genetic testing will
      not be required in integrase inhibitor-naive patients. The drug is well tolerated
      and associated with few treatment discontinuations. It can be administered once
      daily and the tablet size is small. A fixed-dose combination tablet containing
      dolutegravir, abacavir and lamivudine will soon be available. Dolutegravir has
      few interactions with commonly-used drugs. It does not require pharmacological
      boosting and has no food or time of day restrictions. Because of these
      characteristics, dolutegravir has a unique profile and is the ideal drug for most
      HIV-infected patients.

PMID- 25858611
TI  - Substrate Selectivities and Catalytic Activities of Marmoset Liver Cytochrome
      P450 2A6 Differed from Those of Human P450 2A6.
AB  - The common marmoset (Callithrix jacchus), a New World primate species, is
      potentially a useful animal model for preclinical studies in drug development.
      However, cytochrome P450 (P450) enzymes have not been fully identified and
      characterized in marmosets. In this study, we identified P450 2A6 cDNA with the
      sequence highly identical (91-94%) to human P450 2A6, 2A7, and 2A13 cDNA and
      cynomolgus monkey P450 2A23, 2A24, and 2A26 cDNA. Among the tissue types
      examined, marmoset P450 2A6 mRNA was most abundantly expressed in livers where
      P450 2A6 protein was also detected by immunoblotting. Phylogenetic analysis
      showed that marmoset P450 2A6 was more closely clustered with human and
      cynomolgus monkey P450 2As than P450 2As of dog, rat, and mouse (the species also
      used in drug metabolism). Marmoset P450 2A6 heterologously expressed in
      Escherichia coli membranes efficiently catalyzed 7-ethoxycoumarin O-deethylation,
      similar to human P450 2A6 and 2A13 and cynomolgus monkey P450 2A23, 2A24, and
      2A26, but much less effectively coumarin 7-hydroxylation, showing some difference
      as well. Interestingly, marmoset P450 2A6 and cynomolgus monkey P450 2A23
      catalyzed phenacetin O-deethylation, which is catalyzed by human P450 1A2 and
      2A13, but not by P450 2A6. Marmoset P450 2A6 also exhibited catalytic activity
      toward testosterone by the multiple sites, but not rat P450 2A-specific
      testosterone 7alpha-hydroxylation activity. These results indicated that marmoset
      P450 2A6 had functional characteristics different from those of human and
      cynomolgus monkey P450 2As in terms of partially different substrate
      specificities and catalytic activities, indicating its importance of further
      studies for P450 2A-dependent drug metabolism in marmosets. 

PMID- 25858612
TI  - Ten-Year Safety with Polyacrylamide Gel Used to Correct Facial Lipoatrophy in HIV
      Infected Patients.
AB  - Long-term results (>5 years) for synthetic substances used to repair facial
      lipoatrophy have not been published. We performed a cross-sectional study to
      evaluate the 10-year safety of polyacrylamide hydrogel (Aquamid) among the 751
      patients from our unit who received facial infiltrations at least 10 years ago.
      Epidemiological and clinical data such as complications and patient satisfaction
      were collected. We also identified those patients who presented a facial
      infection at any time after infiltration. A total of 104 patients had received
      Aquamid at least 10 years ago. Before infiltrations, 24.0%, 41.3%, and 34.7%
      presented very severe, severe, and moderate facial lipoatrophy, respectively.
      After a mean (SD) of 10.3 (0.5) years since the infiltrations, 19.2%, 47.7%, and
      31.7% of patients reported moderate, mild, and no signs of facial lipoatrophy.
      The values reported by physicians for the same categories were 1.9%, 10.6%, and
      87.5%. Indurations were detected in 6.7% of patients and nodules in 3.8%. Five
      patients (4.8%) had a local infection. A further 15 patients with a shorter
      follow-up (less than 10 years) presented local infections (overall incidence
      considering the 751 patients who received infiltrations of Aquamid, 2.7%); the
      product had to be withdrawn in three cases. The majority of patients were highly
      satisfied (74.8%) or satisfied (23.4%) with the cosmetic results; among patients
      with severe or very severe lipoatrophy at baseline, 31.4% were satisfied and
      65.7% were highly satisfied. Infiltrations with polyacrylamide hydrogel (Aquamid)
      are a safe strategy for the treatment of facial lipoatrophy in the long term. The
      rate of severe complications was low, and patient satisfaction with the cosmetic
      results was high. However, facial infections may appear in the long term.
      Therefore, HIV-infected patients who received synthetic substances should be
      carefully monitored over time. 

PMID- 25858613
TI  - Pharmacological Inhibition of Protein Kinase G1 Enhances Bone Formation by Human
      Skeletal Stem Cells Through Activation of RhoA-Akt Signaling.
AB  - Development of novel approaches to enhance bone regeneration is needed for
      efficient treatment of bone defects. Protein kinases play a key role in
      regulation of intracellular signal transduction pathways, and pharmacological
      targeting of protein kinases has led to development of novel treatments for
      several malignant and nonmalignant conditions. We screened a library of kinase
      inhibitors to identify small molecules that enhance bone formation by human
      skeletal (stromal or mesenchymal) stem cells (hMSC). We identified H-8 (known to
      inhibit protein kinases A, C, and G) as a potent enhancer of ex vivo osteoblast
      (OB) differentiation of hMSC, in a stage- and cell type-specific manner, without
      affecting adipogenesis or osteoclastogenesis. Furthermore, we showed that
      systemic administration of H-8 enhances in vivo bone formation by hMSC, using a
      preclinical ectopic bone formation model in mice. Using functional screening of
      known H-8 targets, we demonstrated that inhibition of protein kinase G1 (PRKG1)
      and consequent activation of RhoA-Akt signaling is the main mechanism through
      which H-8 enhances osteogenesis. Our studies revealed PRKG1 as a novel negative
      regulator of OB differentiation and suggest that pharmacological inhibition of
      PRKG1 in hMSC implanted at the site of bone defect can enhance bone regeneration.
      Stem Cells 2015;33:2219-2231. 

PMID- 25858614
TI  - Transport properties of pristine few-layer black phosphorus by van der Waals
      passivation in an inert atmosphere.
AB  - Ultrathin black phosphorus is a two-dimensional semiconductor with a sizeable
      band gap. Its excellent electronic properties make it attractive for applications
      in transistor, logic and optoelectronic devices. However, it is also the first
      widely investigated two-dimensional material to undergo degradation upon exposure
      to ambient air. Therefore a passivation method is required to study the intrinsic
      material properties, understand how oxidation affects the physical properties and
      enable applications of phosphorene. Here we demonstrate that atomically thin
      graphene and hexagonal boron nitride can be used for passivation of ultrathin
      black phosphorus. We report that few-layer pristine black phosphorus channels
      passivated in an inert gas environment, without any prior exposure to air,
      exhibit greatly improved n-type charge transport resulting in symmetric electron
      and hole transconductance characteristics. 

PMID- 25858615
TI  - Hypertension and obesity in Italian school children: The role of diet, lifestyle
      and family history.
AB  - BACKGROUND AND AIMS: In Italy, the prevalence of hypertension, obesity and
      overweight in paediatric patients has increased in the past years. The purpose of
      this study was to analyse the relationship between obesity and hypertension and
      related factors in Italian students. METHODS AND RESULTS: We studied 2007 healthy
      individuals between the ages of 6 and 17 years of age (998 males and 1009
      females) attending schools in the cities of Varese (northern Italy), Rome
      (central Italy) and Catanzaro (southern Italy). The blood pressure, weight and
      height of the students were measured. We also assessed their daily intake of
      foods and the amount of physical activity they performed. A questionnaire was
      administered to the parents of the subjects to obtain information on the child's
      medical history and family lifestyle. Of the students, 27.2% were overweight, and
      6.6% were obese, with the highest percentages in southern Italy. A total of 6.2%
      of students had hypertension, and the region with the highest percentage was
      found to be northern Italy. Obese students had a risk of developing hypertension
      that was four times greater than those subjects who were of normal weight.
      CONCLUSION: Overweight and obese children/adolescents were more frequently found
      in southern Italy as opposed to northern and central Italy, and hypertensive
      children were more prevalent in the north. An unhealthy diet might explain the
      more widely spread obesity among children living in the south; an excess use of
      salt could explain the greater rate of hypertension found among
      children/adolescents living in the north.

PMID- 25858616
TI  - Assessment of dyspnoea in the emergency department by numeric and visual scales:
      A pilot study.
AB  - OBJECTIVE(S): Dyspnoea is a common and often debilitating symptom that affects up
      to 50% of patients admitted to acute tertiary care hospitals. The primary purpose
      of this study was to compare the numeric rating scale (NRS) and the visual
      analogue scale (VAS) for dyspnoea evaluation in the ED setting. STUDY DESIGN AND
      PATIENTS: This was a cohort study of patients admitted to the ED in a university
      hospital, with dyspnoea as the chief complaint. METHODS: The agreement of the two
      dyspnoea scales was assessed using the intraclass correlation coefficient (ICC).
      RESULTS: One hundred and seventeen patients were included in this analysis. The
      median age for the whole study population was 67 years and 42% of patients were
      male. The aetiology of dyspnoea was acute heart failure (AHF) in 35% of patients.
      There was good agreement between the two scores (ICC=0.795; 95% CI=0.717-0.853;
      P<0.001). CONCLUSIONS: This pilot study demonstrated that numerical rating and
      visual analogue scales agree well when assessing the severity of dyspnoea in the
      ED. Further studies with larger cohorts of patients are needed to confirm these
      preliminary results.

PMID- 25858617
TI  - Spontaneous uterine rupture at 14 weeks gestation during a pregnancy consecutive
      to an oocyte donation in a woman with Turner's syndrome.
AB  - We describe a spontaneous uterine rupture at 14 weeks gestation in a Turner
      patient. A 39 year-old patient was admitted for abdominal pain and hypotension at
      14 weeks of pregnancy. The pregnancy had been obtained by oocyte donation and in
      vitro fertilization (IVF) because of Turner's syndrome. The abdominal ultrasound
      scan showed a normal pregnancy and a conserved foetal cardiac activity. It also
      showed a large amount of free fluid in the perihepatic space. Haemoglobin was
      11.2 g/dL. After hemodynamic degradation, urgent laparoscopy showed an
      unrepairable uterine rupture with partial exteriorisation of the pregnancy, and
      placenta percreta. Urgent conversion to laparotomy allowed haemostatic
      hysterectomy. Uterine rupture during pregnancy obtained by oocyte donation in
      Turner's syndrome may be life threatening. The possibility of such a complication
      should be considered before oocyte donation for IVF in Turner's patients. Early
      spontaneous uterine rupture (second trimester) is a challenging diagnostic that
      should be evoked in case of non-specific abdominal pain in the presence of risk
      factors.

PMID- 25858618
TI  - Usefulness of the Airtraq DLTM videolaryngoscope for placing a double-lumen tube.
AB  - BACKGROUND: Endotracheal insertion of a double-lumen tube (DLT) may be difficult
      because of its size and shape. The AirtraqTM is a new videolaryngoscope that
      allows supraglottis exposure without needing to align the oro-pharyngo-laryngeal
      axis. A specific model (Airtraq DLTM), with a large diameter, has been
      specifically designed to insert a DLT. We have tested the efficiency of this
      device on the quality of supraglottis exposure and the endotracheal position of
      the DLT. STUDY DESIGN: This was a prospective and observational study. METHODS:
      This study included 37 consecutive patients with no risk for difficult intubation
      and who required insertion of a DLT for one-lung ventilation. The main outcomes
      were the success rate of endotracheal intubation within 120 s, the quality of
      glottis exposure, the position of the tube within the trachea and the occurrence
      of any complications. RESULTS: All patients were safely intubated, but only 33
      (89%) were successfully intubated within 120 s (mean time: 44+/-27 s). Using the
      Airtraq DLTM videolaryngoscope, significantly more patients were graded Cormack
      and Lehane I as compared to the Macintosh laryngoscope (97% vs. 73%, P<0.05).
      Overall, fiberoptic bronchoscopy detected 62% of incorrectly positioned DLTs.
      Blood was noted on the blade of the videolaryngoscope in seven patients,
      desaturation occurred in two patients and labial trauma in one patient.
      CONCLUSION: The use of the Airtraq DLTM improves exposure of the supraglottis
      during insertion of a DLT. However, previous removal of the stylet could increase
      the risk of incorrectly positioning the tube.

PMID- 25858619
TI  - Compatibility of medications during multi-infusion therapy: A controlled in vitro
      study on a multilumen infusion device.
AB  - OBJECTIVE: Drug incompatibilities can jeopardize the safety and effectiveness of
      intravenous drug therapies, especially in the field of anaesthesia and intensive
      care. Patients receive many drugs simultaneously through limited venous accesses.
      This study was designed to confirm the impact of a multilumen infusion device on
      the occurrence of known physical drug incompatibilities. STUDY DESIGN: In vitro
      laboratory work. METHODS: Two infusion devices were studied: a standard single
      lumen set and a multilumen infusion access device (Edelvaiss Multiline-8, Doran
      International). Up to six drugs were infused simultaneously: three acidic
      solutions of midazolam, amiodarone and dobutamine, and three alkaline solutions
      of furosemide, pantoprazole and amoxicillin/clavulanate. Saline, Ringer' solution
      and 5% dextrose were used as hydration vehicles with an infusion rate initially
      set at 100 mL/h and with stepwise decreases of 10 mL/h until precipitation. Two
      methods were used to highlight physical drug compatibility according to the
      European Pharmacopoeia: visual inspection of the extension set and an obscured
      light sub-visible particle count test of infusions. The lowest infusion rate
      value for vehicle infusion to satisfy the two tests in all trials is reported for
      each infusion device. RESULTS: The standard set did not satisfy the test in 82%
      of the assessed drug combinations. The Edelvaiss Multiline-8 was able to prevent
      the occurrence of drug incompatibilities in 49% of the drug combinations tested.
      This device is therefore advantageous, especially when simultaneously infusing
      two or four incompatible drugs. CONCLUSIONS: Infusion device characteristics have
      an impact on physical drug incompatibilities. Our results confirm that the
      Edelvaiss Multiline-8 device prevents physical drug incompatibilities under
      specified conditions.

PMID- 25858620
TI  - A case of circulatory collapse during intravenous immunoglobulin therapy: A
      manageable adverse effect!

PMID- 25858621
TI  - High-frequency percussive ventilation as a rescue therapy for ARDS patients under
      ECMO: About a case.

PMID- 25858622
TI  - Monitoring glutamate levels in the posterior cingulate cortex of thyroid
      dysfunction patients with TE-averaged PRESS at 3T.
AB  - BACKGROUNDS AND OBJECTIVES: Patients with thyroid dysfunction frequently have
      neuropsychiatric complaints such as lack of concentration, poor memory,
      depression, anxiety and mania, which suggest brain dysfunction. However, the
      underlying process of this dysfunction remains unclear. Recent studies of the
      glutamatergic system have offered important insight into the neuropsychiatric
      process. Thus, this study investigates changes in glutamate concentration in
      patients with thyroid dysfunction. It also clarifies whether Glu levels are
      related to thyroid hormones via proton magnetic resonance spectroscopy. METHODS:
      36 untreated patients with thyroid dysfunction (18 hyperthyroidism patients and
      18 hypothyroidism patients) and 18 age- and gender-matched controls were included
      in this study. The posterior cingulate cortex was examined by MRS with TE
      averaged PRESS at 3T. The intensity of glutamate, choline, N-acetylaspartate, and
      creatine was assessed using jMRUI v4.0 software. RESULTS: We found a significant
      difference among hyper-/hypo- and control groups in Glu (P=0.003) and Cho
      (P=0.015). The concentrations of glutamate increased (P=0.006) in the posterior
      cingulate cortex in patients with hypothyroidism and significantly decreased
      (P=0.002) in hyperthyroidism patients relative to controls. There were no
      difference in the concentrations of choline between hyperthyroidism patients and
      controls (P=0.679). Versus the hyperthyroidism group, the hypothyroidism group
      showed increased glutamate (P=0.018) and choline (P=0.001) in the posterior
      cingulate cortex. There was no significant difference in the concentrations of
      NAA or creatine across the three groups (P>0.05). The Glu level correlates with
      TT3 (P=0.000) and FT3 (P=0.022). CONCLUSION: The signal intensity of glutamate
      shows significant differences in the region of the posterior cingulate cortex in
      patients with thyroid dysfunction. This change indicates a potential role of
      glutamate in the brain dysfunction experience by patients with thyroid hormone
      disorders.

PMID- 25858623
TI  - Metal-free cascade cyclization of alkenes toward perfluorinated oxindoles.
AB  - A simple AIBN-mediated cyclization reaction of activated alkenes toward
      perfluorinated oxindoles is developed. In the presence of readily available AIBN,
      N-arylacrylamide and perfluoroalkyl iodides underwent perfluorination reaction to
      give perfluorinated oxindoles in good to excellent yields under metal-free
      conditions. 

PMID- 25858624
TI  - Silencing of Bmi-1 gene enhances chemotherapy sensitivity in human glioblastoma
      cells.
AB  - BACKGROUND: The aim of this study was to determine the influence of the BMI1 gene
      on chemotherapy sensitivity in human glioma cells. MATERIAL/METHODS: The
      expression of the BMI1 gene in 41 cases of human brain glioma was determined by
      quantitative real-time PCR. The silencing effect of RNA interference on the BMI1
      gene was detected by Western blot. Methyl thiazolyl tetrazolium assay (MTT) and
      flow cytometry methods were used to determine the cell viability and apoptosis
      rate of the U251 cells with BMI1 silencing. After those U251 cells were treated
      with Cisplatin (DDP), the cell viability and apoptosis rate were further
      detected. RESULTS: The BMI1 mRNA in glioma was remarkably up-regulated, 176.3% as
      much as that in peri-cancerous tissues (P<0.05). The siRNA-BMI1 significantly and
      effectually inhibited the expression of BMI1 protein (P<0.05). The cell viability
      decreased in U251 cells with BMI1 silenced, and the apoptosis rate upgraded
      significantly (P<0.05 for both). After treating with DDP at various
      concentrations (1, 3, and 5 MUg/ml), the cell viability in the BMI1-slienced U251
      cells was much lower than that in corresponding control U251 cells at each DDP
      concentration (P<0.05 for all), and the apoptosis rate showed the opposite
      changing trends (P<0.05 for all). CONCLUSIONS: There is a notable relationship
      between the over-expression of BMI1 and the carcinogenesis of gliomas. The
      silence of BMI1 inhibited cell proliferation and enhanced the apoptosis of the
      U251 cells, and increased the chemotherapy sensitivity of U251 cells to DDP.

PMID- 25858625
TI  - Charge transport in electrically doped amorphous organic semiconductors.
AB  - This article reviews recent progress on charge generation by doping and its
      influence on the carrier mobility in organic semiconductors (OSs). The doping
      induced charge generation efficiency is generally low in OSs which was explained
      by the integer charge transfer model and the hybrid charge transfer model. The
      ionized dopants formed by charge transfer between hosts and dopants can act as
      Coulomb traps for mobile charges, and the presence of Coulomb traps in OSs
      broadens the density of states (DOS) in doped organic films. The Coulomb traps
      strongly reduce the carrier hopping rate and thereby change the carrier mobility,
      which was confirmed by experiments in recent years. In order to fully understand
      the doping mechanism in OSs, further quantitative and systematic analyses of
      charge transport characteristics must be accomplished.

PMID- 25858626
TI  - Cytotoxic constituents from the seeds of Vietnamese Caesalpinia sappan.
AB  - CONTEXT: Caesalpinia sappan Linn. (Leguminosae) has been used in folk medicines
      for the treatment of many diseases. The heartwood of this plant contains various
      phenolic components with interesting biological applications; however, the
      chemical and biological potentials of the seed of this plant have not been fully
      explored. OBJECTIVE: This study identified the cytotoxic activity of compounds
      from the seeds of C. sappan. MATERIALS AND METHODS: The methanol extract of the
      seed of C. sappan was suspended in H2O and then partitioned with CH2Cl2, EtOAc,
      and n-BuOH, successively. Diterpenoid compounds were isolated from the CH2Cl2
      soluble fraction by silica gel column chromatography methods using organic
      solvents. The compound structures were determined by detailed analysis of NMR and
      MS spectral data. Cytotoxic activity was measured using a modified MTT assay
      against HL-60, HeLa, MCF-7, and LLC cancer cells. The activation of caspase-3
      enzyme and western blotting assay were performed to confirm inhibitory mechanism
      of active compound. RESULTS: Five cassane-type diterpenoids were isolated and
      identified as phanginin I (1), phaginin A (2), phanginin D (3), phanginin H (4),
      and phanginin J (5). Compounds 1-4 showed effective inhibition against HL-60
      cells with the IC50 values of 16.4 +/- 1.5, 19.2 +/- 2.0, 11.7 +/- 1.6, and 22.5
      +/- 5.1 MUM. Compounds 1-3 exhibited cytotoxic activity against HeLa cells with
      the IC50 values of 28.1 +/- 3.6, 37.2 +/- 3.4, and 22.7 +/- 2.8 MUM. Treatment of
      HL-60 cell lines with various concentrations of 3 (0-30 MUM) resulted in the
      growth inhibition and induction of apoptosis. CONCLUSION: These findings
      demonstrate that compound 3 (phanginin D) is one of the main active components of
      the seed of C. sappan activating caspases-3 which contribute to apoptotic cell
      death.

PMID- 25858627
TI  - Prospective comparative study of inhibitory control test and psychometric hepatic
      encephalopathy score for diagnosis and prognosis of minimal hepatic
      encephalopathy in cirrhotic patients in the Indian subcontinent.
AB  - OBJECTIVE: This study aimed to determine the usefulness of inhibitory control
      test (ICT) for diagnosing minimal hepatic encephalopathy (MHE) in the Indian
      subcontinent and its correlation with the severity of liver disease and to
      determine its prognostic significance. METHODS: Two hundred patients with
      cirrhosis and 200 healthy controls were enrolled. Only patients were administered
      with psychometric hepatic encephalopathy score (PHES), while both patients and
      controls were subjected to ICT. MHE was diagnosed when PHES <= -5. ICT was
      considered abnormal when the numbers of ICT lures were >= 14. RESULTS: Overall,
      135 (67.5%) patients had MHE. Mean ICT lures were higher in cirrhotic patients
      with MHE than those without MHE (17.27, 95% confidence interval [CI] 13.9-22.3 vs
      8.79, 95% CI 6.8-12.60, P < 0.001). Target accuracy was lower in patients with
      MHE than in those without (84.35, 95% CI 78.5-89.8 vs 95.36, 95% CI 90.1-99.2, P
      < 0.001). ICT had a sensitivity of 92.6% and specificity of 78.5% with the area
      under the receiver operating characteristic curve of 0.855 (95% CI 0.791-0.920)
      for MHE. ICT was correlated with Child-Turcotte-Pugh class (P < 0.001) and the
      model for end-stage liver disease score (P < 0.001) and predicted the development
      of overt hepatic encephalopathy (OHE) and probable survival with excellent test
      retest reliability. CONCLUSIONS: ICT is useful for diagnosing MHE in patients
      with cirrhosis. It is correlated with disease severity and predicts the
      development of OHE and probable survival with excellent test-retest reliability.

PMID- 25858628
TI  - Informal caregivers' needs on discharge from the spinal cord unit: analysis of
      perceptions and lived experiences.
AB  - PURPOSE: Spinal cord injuries (SCI) are one of the most complex and disabling
      diseases, implying severe consequences on aspects of life of people affected by
      SCI and their caregivers. The aim of our study was to explore the situation of
      informal caregivers of persons with SCI when discharged home from a SCI Unit, in
      relation to needs, emotional experiences, difficulties and subsequent reactions
      to discharge. METHODS: A purposive sample of 11 caregivers were interviewed on
      patients' discharge home from the Spinal Injury Care Unit and at 6 months. The
      semi-structured interviews were analyzed using a qualitative phenomenological
      methodology as described by Giorgi. RESULTS: Five main themes emerged from the
      caregivers' experiences including their implicit and explicit needs. Problems
      concerning communication with healthcare professionals and the need for an
      adequate multidisciplinary taking charge of caregivers in order to support their
      new role emerged within all the themes. CONCLUSIONS: Results suggest that greater
      caregiver involvement in the rehabilitation process and their preparation for
      discharge are required. Communication with healthcare professionals needs to be
      enhanced. It would be useful to organize follow-up visits after discharge to
      assess intervention effectiveness. IMPLICATIONS FOR REHABILITATION: Understanding
      the importance of discharge from the spinal cord unit as a meaningful step in the
      rehabilitation path for both patients and their informal caregivers. Orientating
      healthcare professionals towards a better caregiver involvement during the
      rehabilitation process. Promoting rehabilitation interventions addressed to the
      patients and their caregivers concerning supportive communication strategies as
      well as providing meaningful information, psychological and social support,
      educational intervention besides the physical aspects of care. Understanding SCI
      survivors caregivers' needs can assist healthcare professionals in planning and
      improving taking charge of this core aspect of nursing care.

PMID- 25858629
TI  - Reflecting on 'Choice policies in Northern European health systems'.

PMID- 25858630
TI  - Mesenchymal stem cells suppress fibroblast proliferation and reduce skin fibrosis
      through a TGF-beta3-dependent activation.
AB  - Recent studies showed that transplantation of mesenchymal stem cells (MSCs)
      significantly decreased tissue fibrosis; however, little attention has been paid
      to its efficacy on attenuating skin fibrosis, and the mechanism involved in its
      effect is poorly understood. In this work, we investigated the effects of MSCs on
      keloid fibroblasts and extracellular matrix deposition through paracrine actions
      and whether the antifibrotic properties of MSCs involved transforming growth
      factor-beta (TGF-beta)-dependent activation. In vitro experiments showed that
      conditioned media (CM) from MSCs decreased viability, a-smooth muscle actin
      expression, and collagen secretion of human keloid fibroblasts. In addition, TGF
      beta3 secreted by MSCs was expressed at high level under inflammatory
      environment, and blocking the activity of TGF-beta3 apparently antagonized the
      suppressive activity of MSC CM, which demonstrated that TGF-beta3 played a
      preponderant role in preventing collagen accumulation. In vivo studies showed
      that MSC CM infusion in a mouse dermal fibrosis model induced a significant
      decrease in skin fibrosis. Histological examination of tissue sections and
      immunohistochemical analysis for alpha-smooth muscle actin revealed that TGF
      beta3 of CM-mediated therapeutic effects could obviously attenuate matrix
      production and myofibroblast proliferation and differentiation. These findings
      suggest that TGF-beta3 mediates the attenuating effect of MSCs on both the
      proliferation and extracellular matrix production of human keloid fibroblasts and
      decreases skin fibrosis of mouse model, thus providing new understanding and MSC
      based therapeutic strategy for cutaneous scar treatment. 

PMID- 25858631
TI  - 'I still have no idea why this patient was here': An exploration of the
      difficulties GP trainees experience when gathering information.
AB  - OBJECTIVE: Collecting information during patient encounters is essential for the
      delivery of patient-centered care. To obtain insight into areas that require more
      attention in medical communication training, this study explores what
      difficulties GP trainees encounter when gathering information. METHODS: In this
      phenomenological study, we observed a morning clinic of 15 GP trainees. To
      explore trainees' experiences with information-gathering, we held brief
      interviews after every consultation and a lengthier interview directly after the
      morning clinic. The resulting data were analyzed using template analysis.
      RESULTS: From trainees' reflections, we distilled five difficulties that trainees
      experience when gathering information: (1) Goal conflicts; (2) Ineffectiveness of
      trained communication skills in specific situations; (3) Trainees' distress
      hampers open communication; (4) Untrustworthy information; (5) Tunnel vision.
      CONCLUSION: Information-gathering is difficult for GP trainees. Current generic
      communication skills training does not seem to support trainees sufficiently to
      handle effectively the challenges they encounter during consultations. PRACTICE
      IMPLICATIONS: Medical communication training needs to support trainees in
      handling their goal-conflicts and feelings that hamper information-gathering,
      while also providing them with communication strategies adapted to handling
      specific challenging situations.

PMID- 25858632
TI  - Promoting mammography screening among Chinese American women using a message
      framing intervention.
AB  - OBJECTIVES: This study examined the role of women's perceptions about the
      relative pros versus cons (decisional balance) of mammography in moderating
      Chinese American women's responses to gain- and loss-framed messages that promote
      mammography. METHODS: One hundred and forty-three Chinese American women who were
      currently nonadherent to guidelines for receiving annual screening mammograms
      were randomly assigned to read either a gain- or loss-framed culturally
      appropriate print brochure about mammography screening. Mammography screening was
      self-reported at a 2-month follow-up. RESULTS: Although there was not a main
      effect for message frame, the hypothesized interaction between message frame and
      decisional balance was significant, indicating that women who received a framed
      message that matched their decisional balance were significantly more likely to
      have obtained a mammogram by the follow-up than women who received a mismatched
      message. CONCLUSIONS: Results suggest that decisional balance, and more
      generally, perceptions about mammography, may be an important moderator of
      framing effects for mammography among Chinese American women. PRACTICE
      IMPLICATIONS: The match between message frame and decisional balance should be
      considered when attempting to encourage Chinese American women to receive
      mammography screening, as a match between the two may be most persuasive.

PMID- 25858633
TI  - Effectiveness of motivational interviewing to improve therapeutic adherence in
      patients over 65 years old with chronic diseases: A cluster randomized clinical
      trial in primary care.
AB  - OBJECTIVE: To evaluate the effectiveness of motivational interviewing (MI) in
      improving medication adherence in older patients being treated by polypharmacy.
      METHODS: Cluster randomized clinical trial in 16 primary care centers with 27
      health care providers and 154 patients. Thirty-two health care providers were
      assigned to an experimental (EG) or control group (CG). INTERVENTIONS: MI
      training program and review of patient treatments. Providers in the EG carried
      out MI, whereas those in the CG used an "advice approach". Three follow-up visits
      were completed, at 15 days and at 3 and 6 months. Medication adherence in both
      groups was compared (p<0.05). RESULTS: Patients recruited: 70/84 (EG/CG). Mean
      age: 76 years; female: 68.8%. The proportion of subjects changing to adherence
      was 7.6% higher in the EG (p<0.001). Therapeutic adherence was higher for
      patients in the EG (OR=2.84), women (OR=0.24) and those with high educational
      levels (OR=3.93). CONCLUSION: A face-to-face motivational approach in primary
      care helps elderly patients with chronic diseases who are being treated by
      polypharmacy to achieve an improved level of treatment adherence than traditional
      strategies of providing information and advice. PRACTICE IMPLICATIONS: MI is a
      patient-centered approach that can be used to improve medication adherence in
      primary care. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov
      (NCT01291966).

PMID- 25858634
TI  - Changing knowledge, attitudes, and behaviors regarding cervical cancer screening:
      The effects of an educational intervention in rural Kenya.
AB  - OBJECTIVE: Cervical cancer screening uptake may be influenced by inadequate
      knowledge in resource-limited settings. This randomized trial evaluated a health
      talk's impact on cervical cancer knowledge, attitudes, and screening rates in
      rural Kenya. METHODS: 419 women attending government clinics were randomized to
      an intervention (N=207) or control (N=212) group. The intervention was a brief
      health talk on cervical cancer. Participants completed surveys at enrollment
      (all), immediately after the talk (intervention arm), and at three-months follow
      up (all). The primary outcomes were the change in knowledge scores and the final
      screening rates at three-months follow-up. Secondary outcomes were changes in
      awareness about cervical cancer screening, perception of personal cervical cancer
      risk, cervical cancer and HIV stigma, and screening acceptability. RESULTS: Mean
      Knowledge Scores increased by 26.4% (8.7 points increased to 11.0 points) in the
      intervention arm compared to only 17.6% (8.5 points increased to 10.0 points) in
      the control arm (p<0.01). Screening uptake was moderate in both the intervention
      (58.9%; N=122) and control (60.9%; N=129) arms, with no difference between the
      groups (p=0.60). CONCLUSION: A brief health talk increased cervical cancer
      knowledge, although it did not increase screening over simply informing women
      about free screening. PRACTICAL IMPLICATIONS: Screening programs can increase
      patient understanding with just a brief educational intervention.

PMID- 25858635
TI  - Does N-terminal pro-brain natriuretic peptide correlate with measured shunt
      fraction in children with septal defects?
AB  - BACKGROUND: The aim of this study was to investigate the potential role of N
      terminal pro-brain natriuretic peptide in the assessment of shunt severity and
      invasive haemodynamic parameters in children with atrial septal defects and
      ventricular septal defects. METHODS: This is a prospective, controlled (n:62),
      observational study. Correlation analysis was performed between N-terminal pro
      brain natriuretic peptide levels and various invasive haemodynamic measurements
      in 127 children (ventricular septal defect: 64; atrial septal defect: 63). A
      ratio of pulmonary to systemic blood flow (Qp/Qs?1.5) was considered to indicate
      a significant shunt. RESULTS: Statistically significant relationship was found
      between the mean N-terminal pro-brain natriuretic peptide values of the patients,
      with Qp/Qs?1.5 in both defect types and control group. For ventricular septal
      defect, N-terminal pro-brain natriuretic peptide level?113.5 pg/ml was associated
      with high specificity and sensitivity for determining the significant shunt. In
      addition, the cut-off point for determining the significant shunt for atrial
      septal defect was 57.9 pg/ml. Significant positive correlation was found between
      all invasive haemodynamic parameters and N-terminal pro-brain natriuretic peptide
      levels in patients with ventricular septal defects. Whereas significant positive
      correlation was found only between mean pulmonary artery pressure, right
      ventricular end-diastolic pressure, and systemic pressure to pulmonary pressure
      ratio and N-terminal pro-brain natriuretic peptide levels in patients with atrial
      septal defects. CONCLUSION: Our study demonstrated that the N-terminal pro-brain
      natriuretic peptide measurements could be used as a supporting parameter in
      determining significance of the shunt.

PMID- 25858636
TI  - Outcomes after combined use of intraoperative MRI and 5-aminolevulinic acid in
      high-grade glioma surgery.
AB  - BACKGROUND: Previous studies have shown the individual benefits of 5
      aminolevulinic acid (5-ALA) and intraoperative (i)MRI in enhancing survival for
      patients with high-grade glioma. In this retrospective study, we compare rates of
      progression-free and overall survival between patients who underwent surgical
      resection with the combination of 5-ALA and iMRI and a control group without
      iMRI. METHODS: In 200 consecutive patients with high-grade gliomas, we recorded
      age, sex, World Health Organization tumor grade, and pre- and postoperative
      Karnofsky performance status (good >=80 and poor <80). A 0.15-Tesla magnet was
      used for iMRI; all patients operated on with iMRI received 5-ALA. Overall and
      progression-free survival rates were compared using multivariable regression
      analysis. RESULTS: Median overall survival was 13.8 months in the non-iMRI group
      and 17.9 months in the iMRI group (P = .043). However, on identifying confounding
      variables (ie, KPS and resection status) in this univariate analysis, we then
      adjusted for these confounders in multivariate analysis and eliminated this
      distinction in overall survival (hazard ratio: 1.23, P = .34, 95% CI: 0.81,
      1.86). Although 5-ALA enhanced the achievement of gross total resection (odds
      ratio: 3.19, P = .01, 95% CI: 1.28, 7.93), it offered no effect on overall or
      progression-free survival when adjusted for resection status. CONCLUSIONS: Gross
      total resection is the key surgical variable that influences progression and
      survival in patients with high-grade glioma and more likely when surgical
      adjuncts, such as iMRI in combination with 5-ALA, are used to enhance resection.

PMID- 25858637
TI  - Mother's education and adverse birth outcomes.

PMID- 25858638
TI  - Association between delayed bedtime and sleep-related problems among community
      dwelling 2-year-old children in Japan.
AB  - BACKGROUND: Although delayed sleep timing causes many socio-psycho-biological
      problems such as sleep loss, excessive daytime sleepiness, obesity, and impaired
      daytime neurocognitive performance in adults, there are insufficient data showing
      the clinical significance of a 'night owl lifestyle' in early life. This study
      examined the association between habitual delayed bedtime and sleep-related
      problems among community-dwelling 2-year-old children in Japan. METHODS:
      Parents/caregivers of 708 community-dwelling 2-year-old children in Nishitokyo
      City, Tokyo, participated in the study. The participants answered a questionnaire
      to evaluate their child's sleep habits and sleep-related problems for the past 1
      month. RESULTS: Of the 425 children for whom complete data were collected, 90
      (21.2%) went to bed at 22:00 or later. Children with delayed bedtime showed
      significantly more irregular bedtime, delayed wake time, shorter total sleep
      time, and difficulty in initiating and terminating sleep. Although this
      relationship indicated the presence of sleep debt in children with delayed
      bedtime, sleep onset latency did not differ between children with earlier bedtime
      and those with delayed bedtime. Rather, delayed bedtime was significantly
      associated with bedtime resistance and problems in the morning even when
      adjusting for nighttime and daytime sleep time. CONCLUSIONS: Even in 2-year-old
      children, delayed bedtime was associated with various sleep-related problems. The
      causal factors may include diminished homeostatic sleep drive due to prolonged
      daytime nap as well as diurnal preference (morning or night type) regulated by
      the biological clock.

PMID- 25858639
TI  - A megacolon with a skin lesion.

PMID- 25858640
TI  - Expression of chemokines CXCL4 and CXCL7 by synovial macrophages defines an early
      stage of rheumatoid arthritis.
AB  - BACKGROUND AND OBJECTIVES: For our understanding of the pathogenesis of
      rheumatoid arthritis (RA), it is important to elucidate the mechanisms underlying
      early stages of synovitis. Here, synovial cytokine production was investigated in
      patients with very early arthritis. METHODS: Synovial biopsies were obtained from
      patients with at least one clinically swollen joint within 12 weeks of symptom
      onset. At an 18-month follow-up visit, patients who went on to develop RA, or
      whose arthritis spontaneously resolved, were identified. Biopsies were also
      obtained from patients with RA with longer symptom duration (>12 weeks) and
      individuals with no clinically apparent inflammation. Synovial mRNA expression of
      117 cytokines was quantified using PCR techniques and analysed using standard and
      novel methods of data analysis. Synovial tissue sections were stained for CXCL4,
      CXCL7, CD41, CD68 and von Willebrand factor. RESULTS: A machine learning approach
      identified expression of mRNA for CXCL4 and CXCL7 as potentially important in the
      classification of early RA versus resolving arthritis. mRNA levels for these
      chemokines were significantly elevated in patients with early RA compared with
      uninflamed controls. Significantly increased CXCL4 and CXCL7 protein expression
      was observed in patients with early RA compared with those with resolving
      arthritis or longer established disease. CXCL4 and CXCL7 co-localised with blood
      vessels, platelets and CD68(+) macrophages. Extravascular CXCL7 expression was
      significantly higher in patients with very early RA compared with longer duration
      RA or resolving arthritis CONCLUSIONS: Taken together, these observations suggest
      a transient increase in synovial CXCL4 and CXCL7 levels in early RA.

PMID- 25858642
TI  - Paracetamol: is all the concern valid?

PMID- 25858641
TI  - Nintedanib inhibits fibroblast activation and ameliorates fibrosis in preclinical
      models of systemic sclerosis.
AB  - BACKGROUND: Nintedanib is a tyrosine kinase inhibitor that has recently been
      shown to slow disease progression in idiopathic pulmonary fibrosis in two
      replicate phase III clinical trials. The aim of this study was to analyse the
      antifibrotic effects of nintedanib in preclinical models of systemic sclerosis
      (SSc) and to provide a scientific background for clinical trials in SSc. METHODS:
      The effects of nintedanib on migration, proliferation, myofibroblast
      differentiation and release of extracellular matrix of dermal fibroblasts were
      analysed by microtitre tetrazolium and scratch assays, stress fibre staining,
      qPCR and SirCol assays. The antifibrotic effects of nintedanib were evaluated in
      bleomycin-induced skin fibrosis, in a murine sclerodermatous chronic graft-versus
      host disease model and in tight-skin-1 mice. RESULTS: Nintedanib dose-dependently
      reduced platelet-derived growth factor-induced and transforming growth factor
      beta-induced proliferation and migration as well as myofibroblast differentiation
      and collagen release of dermal fibroblasts from patients with and healthy
      individuals. Nintedanib also inhibited the endogenous activation of SSc
      fibroblasts. Nintedanib prevented bleomycin-induced skin fibrosis in a dose
      dependent manner and was also effective in the treatment of established fibrosis.
      Moreover, treatment with nintedanib ameliorated fibrosis in the chronic graft
      versus-host disease model and in tight-skin-1 mice in well-tolerated doses.
      CONCLUSIONS: We demonstrate that nintedanib effectively inhibits the endogenous
      as well as cytokine-induced activation of SSc fibroblasts and exerts potent
      antifibrotic effects in different complementary mouse models of SSc. These data
      have direct translational implications for clinical trials with nintedanib in
      SSc.

PMID- 25858643
TI  - The effects of a brace for patellofemoral osteoarthritis targeting knee pain and
      bone marrow lesions were overestimated or not?

PMID- 25858644
TI  - Chemical feasibility of the general acid/base mechanism of glmS ribozyme self
      cleavage.
AB  - In numerous Gram-positive bacteria, the glmS ribozyme or catalytic riboswitch
      regulates the expression of glucosamine-6-phosphate (GlcN6P) synthase via site
      specific cleavage of its sugar-phosphate backbone in response to GlcN6P ligand
      binding. Biochemical data have suggested a crucial catalytic role for an active
      site guanine (G40 in Thermoanaerobacter tengcongensis, G33 in Bacillus
      anthracis). We used hybrid quantum chemical/molecular mechanical (QM/MM)
      calculations to probe the mechanism where G40 is deprotonated and acts as a
      general base. The calculations suggest that the deprotonated guanine G40(-) is
      sufficiently reactive to overcome the thermodynamic penalty arising from its rare
      protonation state, and thus is able to activate the A-1(2'-OH) group toward
      nucleophilic attack on the adjacent backbone. Furthermore, deprotonation of A
      1(2'-OH) and nucleophilic attack are predicted to occur as separate steps, where
      activation of A-1(2'-OH) precedes nucleophilic attack. Conversely, the transition
      state associated with the rate-determining step corresponds to concurrent
      nucleophilic attack and protonation of the G1(O5') leaving group by the ammonium
      moiety of the GlcN6P cofactor. Overall, our calculations help to explain the
      crucial roles of G40 (as a general base) and GlcN6P (as a general acid) during
      glmS ribozyme self-cleavage. In addition, we show that the QM/MM description of
      the glmS ribozyme self-cleavage reaction is significantly more sensitive to the
      size of the QM region and the quality of the QM-MM coupling than that of other
      small ribozymes.

PMID- 25858645
TI  - Impact of persistent minimal residual disease post-consolidation therapy in
      children and adolescents with advanced Burkitt leukaemia: a Children's Oncology
      Group Pilot Study Report.
AB  - Patient-specific primers from 10 children/adolescents with Burkitt leukaemia (BL)
      +/- central nervous system disease who were treated with French-British
      American/Lymphome Malins de Burkitt 96 C1 plus rituximab were developed from
      diagnostic blood/bone marrow. Minimal residual disease (MRD) was assessed by real
      time polymerase chain reaction at the end of induction (EOI) and consolidation
      (EOC). Seventy per cent (7/10) and 71% (5/7) were MRD-positive at EOI and EOC,
      respectively, with no disease recurrences. MRD after induction and consolidation
      did not predict relapse and subsequent therapy appeared to eliminate MRD. Thus,
      assessing MRD at a later time point is warranted in future trials to determine
      its clinical significance. 

PMID- 25858648
TI  - Yoga therapy research, individualized yoga therapy and call it yoga therapy.
AB  - Three independent perspectives on Yoga therapy research, Individualized yoga
      therapy and the current controversy over nomenclature for our field, i.e., yoga
      therapy vs. medical yoga. 

PMID- 25858647
TI  - The differences between yoga teacher training and yoga therapist training and the
      distinction between yoga teaching and yoga therapy.
AB  - This is a set of invited perspectives on two key policy issues: The Differences
      Between Yoga Teacher Training and Yoga Therapist Training and the Distinction
      Between Yoga Teaching and Yoga Therapy. 

PMID- 25858649
TI  - Measuring the effect of an eight-week adaptive yoga program on the physical and
      psychological status of individuals with Parkinson's disease. A pilot study.
AB  - Parkinson's disease (PD) is a neurodegenerative disease that affects muscle tone,
      strength, flexibility, motor control, psychological outlook, cognition, and
      function. Exercise has been found to improve physical ability and psychological
      outlook, but the effect of yoga on individuals with PD has not been well
      researched. The purposes of this study were to identify outcome measures that
      were responsive to change in individuals with PD after an 8-week adaptive yoga
      program and to determine appropriate sample sizes for future studies. In a
      repeated measures design, 10 participants with a Hoehn and Yahr stage of 2 or 3
      were tested prior to and after an 8-week control phase and again after they
      underwent an 8-week adaptive yoga program. Analysis of variance (ANOVA) tests
      revealed differences in time of measure that approached significance for the
      depression subscale of the Hospital Anxiety and Depression Scale (HADS) (p =
      0.008) and the 30-Second Chair Stand (TSCS) (p = 0.013). The interaction between
      time of measure and gender approached significance for the Sit-and-Reach Test
      (SRT) (p = 0.08 and 0.03, right and left respectively), with male participants
      improving in sit-and-reach flexibility compared with female participants after
      intervention. The interaction between time of measure and age approached
      significance for the Single-Leg Balance test (SLB) (p = 0.007), with younger
      participants improving in SLB time after intervention. Power calculations found
      that a sample size ranging from 33 to 153 would be required to achieve
      significance at the 0.01 level in the various outcome measures in a future study
      of this design. The depression subscale of the HADS, the TSCS, the SLB, and the
      right and left SRT were the measures that changed following the yoga intervention
      and are recommended as outcome measures in future studies investigating the
      effectiveness of yoga for individuals with PD. This preliminary study supports
      further investigation of adaptive yoga using a randomized design and a larger
      sample size of individuals with PD. 

PMID- 25858650
TI  - A preliminary investigation of lumbar tactile acuity in yoga practitioners.
AB  - BACKGROUND: Tactile acuity in the back relates to voluntary lumbo-pelvic control
      and is lower in chronic low back pain (CLBP) patients. Two-point discrimination
      (TPD) thresholds are higher, indicating decreased tactile acuity in patients with
      CLBP. Yoga has been shown to help relieve CLBP. OBJECTIVES: This study
      investigated the hypothesis that regular practitioners of yoga have increased
      tactile acuity (i.e., lower TPD thresholds) when compared to matched controls who
      regularly perform gym-based (resistance training or aerobic-type) exercise.
      METHOD: Tactile acuity in the low back was assessed using TPD in 16 long-term
      practitioners of yoga (5 Ashtanga, 5 Bikram, and 6 Iyengar practitioners) and 16
      age- and gender-matched healthy controls who exercise (with weights and aerobic
      exercise). RESULTS: The yoga practitioners' TPD was lower than that of the
      exercisers, indicating greater tactile acuity in the low back. While there was no
      difference between the TPD of the practitioners of different yoga styles, the TPD
      of the Ashtanga yoga participants were significantly lower than those of the
      exercisers. The yogis whose main reasons to practice yoga were for "meditation or
      increased mindfulness" and for "well-being" showed a nonsignificant trend of
      higher tactile acuity than those who did yoga for "physical exercise." There was
      no association between TPD threshold and cumulative amount of yoga practice in
      terms of hours per week and years of experience. However, increased hours of
      exercise per week correlated with higher TPD. CONCLUSION: The findings suggest
      that there may be a relationship between yoga practice and enhanced tactile
      acuity in the low back.

PMID- 25858651
TI  - Delivering Integrative Restoration-Yoga Nidra Meditation (iRest(r)) to Women with
      Sexual Trauma at a Veteran's Medical Center: A Pilot Study.
AB  - OBJECTIVE: This pilot study examines iRest, a form of guided mindfulness
      meditation, and its ability to reduce symptoms associated with sexual trauma,
      including military sexual trauma (MST), in a sample of women seeking
      psychotherapy services at a Department of Veterans Affairs (VA) medical center.
      METHODS: 90-minute sessions were held 19 times, twice a week for 10 weeks, except
      for the week with a holiday. Participants completed self-report measures Brief
      Symptom Inventory-18 (BSI), Posttraumatic Cognitions Inventory (PTCI), and the
      Post-traumatic Stress Disorder Check List (PCL) pre- and post-treatment. Sixteen
      women were recruited: 15 enrolled, 5 dropped due to transportation issues, and 10
      completed the protocol. RESULTS: Completers reported significant decreases in
      symptoms of posttraumatic stress disorder (PCL, t (9) = 3.17, p < 0.01, d =
      0.66), negative thoughts of self-blame (PTCI t (9) = 2.96, p < 0.05, d = 0.52),
      and depression (BSI, t (9) = 2.33, p < 0.05, d = 0.64). Participants also offered
      verbal reports of decreased body tension, improved quality of sleep, improved
      ability to handle intrusive thoughts, improved ability to manage stress, and an
      increased feeling of joy. Participants also enthusiastically endorsed the class
      and stated they would take it again and recommend it to others. CONCLUSIONS: This
      small pilot study showed promising results for delivering iRest to women with
      sexual trauma in a VA medical center. Further research is warranted.

PMID- 25858652
TI  - Acute and Cumulative Effects of Vinyasa Yoga on Affect and Stress among College
      Students Participating in an Eight-week Yoga Program: A Pilot Study.
AB  - BACKGROUND: College students are vulnerable to a critical period in developmental
      maturation, facing rigorous academic work and learning how to function
      independently. Western aerobic exercise (WAE), such as running and bicycling, has
      been shown to improve mood and relieve stress. However, college students often
      have low levels of physical activity. Yoga is an ancient physical and mental
      practice that may affect mood and stress. However, rigorous studies examining the
      psychological effects of yoga are rare in peerreviewed Western journals. The aim
      of this research was to establish preliminary evidence for the acute effects of
      Vinyasa yoga on affect and stress in young-adult college students. METHODS:
      Twenty healthy college students age 18 years and older were recruited to
      participate in this pilot study. Participants attended a Vinyasa yoga class at a
      local studio twice weekly for 8 weeks. Affect and stress were assessed before and
      after each yoga session. Measures included the Positive and Negative Affective
      Schedule (PANAS) and the Cohen Perceived Stress scale. RESULTS: Positive affect
      scores increased significantly (p < 0.05) for 14 of the 16 yoga sessions (mean
      increase = 23.2%). Negative affect decreased significantly from pre- to postyoga
      (p < 0.05) for 15 of the 16 sessions (mean decrease = 22%). Repeated measures
      ANOVAs examining pre-post composite scores across all 8 weeks showed significant
      changes in PANAS, but not stress scores. CONCLUSIONS: Findings suggest that yoga
      practice is associated with acute improvements in affect in a young-adult college
      population. Future research is needed to examine the extent to which different
      types of yoga address the needs of different college sub-populations (e.g.,
      eating disordered, overweight/obese, sedentary, and smokers).

PMID- 25858653
TI  - Flexibility of the elderly after one-year practice of yoga and calisthenics.
AB  - Flexibility training responses to distinct stretching techniques are not well
      defined, especially in the elderly. This study compared the flexibility of
      elderly individuals before and after having practiced hatha yoga and calisthenics
      for 1 year (52 weeks), at least 3 times/week. Sixty-six subjects (12 men)
      measured and assigned to 3 groups: control (n = 24, age = 67.7+/-6.9 years),
      hatha yoga (n = 22, age = 61.2+/-4.8 years), and calisthenics (n = 20, age =
      69.0+/-5.8 years). The maximal range of passive motion of 13 movements in 7
      joints was assessed by the Flexitest, comparing the range obtained with standard
      charts representing each arc of movement on a discontinuous and non-dimensional
      scale from 0 to 4. Results of individual movements were summed to define 4
      indexes (ankle+knee, hip+trunk, wrist+elbow, and shoulder) and total flexibility
      (Flexindex). Results showed significant increases of total flexibility in the
      hatha yoga group (by 22.5 points) and the calisthenics group (by 5.8 points) (p <
      0.01 for each) and a decrease in the control group (by 2.1 points) (p < 0.01)
      after one year of intervention. Between-group comparison showed that increases in
      the hatha yoga group were greater than in the calisthenics group for most
      flexibility indexes, particularly the overall flexibility (p <0.05). In
      conclusion, the practice of hatha yoga (i.e., slow/passive movements) was more
      effective in improving flexibility compared to calisthenics (i.e., fast/dynamic
      movements), but calisthenics was able to prevent flexibility losses observed in
      sedentary elderly subjects. 

PMID- 25858654
TI  - Self-reported morningness-eveningness related to positive affect-change
      associated with a single session of hatha yoga.
AB  - OBJECTIVES: To examine positive affect (PA) responses to a single hatha yoga
      session compared to a lecture control class and to investigate a potential
      association between selfreported morningness-eveningness and yoga - related PA
      change. METHOD: Participants (Mean age = 28.50 years) in the yoga group (n = 45)
      and control group (n = 25) completed the revised Morningness-Eveningness
      Questionnaire (rMEQ) before yoga and lecture (pre) and the Visual Analogue Mood
      Scale (VAMS) as a measure of PA before and after yoga and lecture (post).
      RESULTS: Pre-to-post PA change was greater in the yoga group compared to the
      control (p < 0.001). Analysis of the yoga group VAMS scores revealed a
      significant rMEQ type (morning, neither, evening) by time (pre to post)
      interaction (p = 0.03), with greater PA change in evening types compared to
      morning types (p = 0.01). CONCLUSIONS: The results show that a single hatha yoga
      session improves self-reported PA more than a lecture control and suggest a
      relationship between self-reported morningness-eveningness and PA responses to
      hatha yoga. The findings may help yoga practitioners, instructors, and
      researchers better understand the psychological benefits of yoga. Researchers
      should consider conducting long-term studies on the association between self
      reported morningness- eveningness and affective responses to yoga practice.

PMID- 25858655
TI  - Implementing yoga therapy adapted for older veterans who are cancer survivors.
AB  - OBJECTIVES: This goal of this paper is to describe the reach, application, and
      effectiveness of an 8-week yoga therapy protocol with older cancer survivors
      within a Veterans Health Administration setting. METHODS: To document the reach
      of this intervention, recruitment efforts, attendance, and practice rates were
      tracked. To explore the application of the protocol to this population, physical
      therapy preassessment and observations by the yoga therapist were recorded to
      ascertain necessary pose modifications. Effectiveness was measured through pre-
      and post-course structured interviews, tracking self-reported symptoms of combat
      related posttraumatic stress disorder, depression, anxiety, fatigue, insomnia,
      and pain. RESULTS: Regarding reach, 15% of eligible veterans (n = 14) enrolled,
      participated in 3-16 classes (M+/-SD = 11.64+/-3.39), and practiced at home for 0
      56 days (M+/-SD = 26.36+/-17.87). Participants were primarily Caucasian (n = 13),
      male (n = 13), ranged in age from 55 to 78 years (M+/-SD = 65.64+/-5.15), and had
      multiple medical problems. During application, substantial individualized
      modifications to the yoga therapy protocol were necessary. Effectiveness of the
      intervention was mixed. During post-course interviews, participants reported a
      variety of qualitative benefits. Notably, the majority of participants reported
      that breathing and relaxation techniques were the most useful to learn. Group
      comparisons of mean pre- and post-course scores on standardized measures showed
      no significant differences. CONCLUSIONS: A minority of older veterans express an
      interest in yoga, but those who do have high rates of class attendance and home
      practice. Careful physical pre-assessment and attentive therapists are required
      to undertake the adaptations required by participants with multiple
      comorbidities. The effectiveness of yoga in this setting requires additional
      study.

PMID- 25858656
TI  - A process evaluation of the art of yoga project mentor program for incarcerated
      teenage girls.
AB  - Returning to the community upon release from custody is a difficult process to
      navigate, and there are scant resources available to juvenile female offenders,
      in particular. Comprehensive wraparound aftercare and mentor services are a
      central component of successful community reentry, and the well-established
      unique characteristics of juvenile girls make it necessary to create programs
      catered specifically to them. The present study employed a case study design to
      describe and evaluate the Art of Yoga Project's Mentor Program. Eight girls and
      their mentors were followed for a period of 12 months after the girls' release
      from custody. Preliminary results from qualitative content analysis suggest that
      the program was valuable for the girls who participated. 

PMID- 25858657
TI  - Incorporating yoga into early childhood programs: exploring staff members'
      perceptions of a classroom-based yoga program.

PMID- 25858658
TI  - Interest in yoga among fibromyalgia patients: an international internet survey.
AB  - Studies in circumscribed clinical settings have reported the adoption of yoga by
      many fibromyalgia (FM) patients. However, it is unclear from existing studies
      which types of yoga practices FM patients are typically engaging in and the
      extent to which they experience yoga as helpful or not. The purpose of this study
      was to survey FM patients in many different regions to inquire about their
      engagement in various yoga practices, the perceived benefits, and the obstacles
      to further practice. A 13-question Internet survey of persons self-identified as
      FM patients was conducted among subscribers to 2 electronic newsletters on the
      topic of FM. Respondents (N = 2543) replied from all 50 U.S. states and also from
      Canada, Australia, and the United Kingdom, and from more than two dozen other
      countries. On average, respondents were 57 years of age and 96% were female, with
      an average time since diagnosis of 13 years. Of these respondents, 79.8% had
      considered trying yoga and 57.8% had attended 1 yoga class. The respondents'
      classes typically focused almost exclusively on yoga poses, with minimal training
      in meditation, breathing techniques, or other practices. The most commonly cited
      benefits were reduced stiffness, relaxation, and better balance. The most
      frequently cited obstacles were concerns about the poses being too physically
      demanding and fear that the poses would cause too much pain. These findings
      confirm strong interest in yoga across a geographically diverse range of FM
      patients. However, concerns about yoga-induced pain and yoga poses being too
      difficult are common reasons that FM patients do not engage in yoga exercises.
      This study supports the need for yoga programs tailored for FM patients to
      include modification of poses to minimize aggravating movements and substantive
      training in meditation and other yoga-based coping methods to minimize pain
      related fear. 

PMID- 25858659
TI  - Yoga as the "next wave" of therapeutic modalities for treatment of insomnia.
AB  - Insomnia rates continue to rise, especially among specific populations. Current
      nonpharmacological treatments rely primarily upon cognitive behavioral therapy
      for insomnia (CBT-I), which was introduced in the 1970s. Newer treatments have
      incorporated CBT "third wave" techniques, including mindfulness and acceptance
      techniques. Yoga practice is well suited to complement existing therapies and to
      address sleep problems in a more holistic way. Current theoretical and empirical
      approaches to treating insomnia are discussed, with an emphasis on the role of
      yoga in addressing precipitating and perpetuating factors in insomnia that have
      previously been largely overlooked.An estimated one-third of U.S. adults suffer
      from insomnia (Chen, Gelaye, & Williams, 2013; Mellinger, Balter, & Uhlenhuth,
      1985; Ohayon, 2002), and the problem appears to be growing. While treatment for
      insomnia has helped to alleviate the problem for some (Irwin, Cole, & Nicassio,
      2006; Morin et al., 2009), prevalence of insomnia is on the rise, especially
      among certain groups, including elderly and military populations (Morin, 2009;
      Mysliwiec et al., 2013). Rising rates of insomnia have been attributed to changes
      in lifestyle and environmental factors, including increased reliance on
      technology and decreased synchrony with natural wake-sleep rhythms (Brahinsky,
      2013; Wallace-Guy et al., 2002; Yun, Bazar, Gerber, Lee, & Daniel, 2005). 

PMID- 25858660
TI  - Convergence vs. Specialization in the ear region of moles (Mammalia).
AB  - We investigated if and how the inner ear region undergoes similar adaptations in
      small, fossorial, insectivoran-grade mammals, and found a variety of inner ear
      phenotypes. In our sample, afrotherian moles (Chrysochloridae) and the marsupial
      Notoryctes differ from most other burrowing mammals in their relatively short
      radii of semicircular canal curvature; chrysochlorids and fossorial talpids share
      a relatively long interampullar width. Chrysochlorids are unique in showing a
      highly coiled cochlea with nearly four turns. Extensive cochlear coiling may
      reflect their greater ecological dependence on low frequency auditory cues
      compared to talpids, tenrecids, and the marsupial Notoryctes. Correspondingly,
      the lack of such extensive coiling in the inner ear of other fossorial species
      may indicate a greater reliance on other senses to enable their fossorial
      lifestyle, such as tactile sensation from vibrissae and Eimer's organs. The
      reliance of chrysochlorids on sound is evident in the high degree of coiling and
      in the diversity of its mallear types, and may help explain the lack of any
      semiaquatic members of that group. The simplest mallear types among
      chrysochlorids are not present in the basal-most members of that clade, but all
      extant chrysochlorids investigated to date exhibit extensive cochlear coiling.
      The chrysochlorid ear region thus exhibits mosaic evolution; our data suggest
      that extensive coiling evolved in chrysochlorids prior to and independently of
      diversification in middle ear ossicle size and shape.

PMID- 25858661
TI  - Review article: gut-directed hypnotherapy in the management of irritable bowel
      syndrome and inflammatory bowel disease.
AB  - BACKGROUND: Gut-directed hypnotherapy is being increasingly applied to patients
      with irritable bowel syndrome (IBS) and to a lesser extent, inflammatory bowel
      disease (IBD). AIM: To review the technique, mechanisms of action and evidence
      for efficacy, and to identify gaps in the understanding of gut-directed
      hypnotherapy as a treatment for IBS and IBD. METHODS: A review of published
      literature and a systematic review of clinical trials in its application to
      patients with IBS and IBD were performed. RESULTS: Gut-directed hypnotherapy is a
      clearly described technique. Its potential mechanisms of action on the brain-gut
      axis are multiple with evidence spanning psychological effects through to
      physiological gastrointestinal modifications. Six of seven randomised IBS studies
      reported a significant reduction (all P < 0.05) in overall gastrointestinal
      symptoms following treatment usually compared to supportive therapy only.
      Response rates amongst those who received gut-directed hypnotherapy ranged
      between 24% and 73%. Efficacy was maintained long-term in four of five studies. A
      therapeutic effect was also observed in the maintenance of clinical remission in
      patients with ulcerative colitis. Uncontrolled trials supported the efficacy and
      durability of gut-directed hypnotherapy in IBS. Gaps in understanding included to
      whom and when it should be applied, the paucity of adequately trained
      hypnotherapists, and the difficulties in designing well controlled-trials.
      CONCLUSIONS: Gut-directed hypnotherapy has durable efficacy in patients with IBS
      and possibly ulcerative colitis. Whether it sits in the therapeutic arsenal as a
      primary and/or adjunctive therapy cannot be ascertained on the current evidence
      base. Further research into efficacy, mechanisms of action and predictors of
      response is required.

PMID- 25858662
TI  - Assessment of trace elements, POPs, (210)Po and stable isotopes ((15)N and (13)C)
      in a rare filter-feeding shark: The megamouth.
AB  - With less than 60 records being reported worldwide, the megamouth (Megachasma
      pelagios) is today one of the least known shark species inhabiting our oceans.
      Therefore, information concerning the biology and ecology of this enigmatic
      organism is very scarce and limited to feeding behaviour and preferred habitat.
      The present work reports new data on the concentrations of trace elements,
      organic mercury, POPs and (210)Po in hepatic and muscular tissues of a specimen
      found stranded in the southeastern coast of Brazil. Additionally, we provide new
      evidence based on stable isotope analysis (delta(15)N and delta(13)C) confirming
      the preference for the pelagic habitat and the zooplanktivorous feeding behaviour
      of the megamouth. These results are consistent with the low concentrations of
      organic pollutant compounds and other elements measured in our samples. 

PMID- 25858663
TI  - Short Communication: Coronary Heart Disease Risk by Framingham Risk Score in
      Hepatitis C and HIV/Hepatitis C-Coinfected Persons.
AB  - We compared the Framingham risk score (FRS) for 10-year coronary heart disease
      (CHD) risk in age- and race-matched hepatitis C virus (HCV)-infected and HCV
      uninfected persons: 114,073 HCV-infected (111,436 HCV-monoinfected and 2,637
      HIV/HCV-coinfected) and 122,996 HCV-uninfected (121,380 HIV and HCV-uninfected
      and 1,616 HIV-monoinfected) males without cardiovascular disease, diabetes, or
      hepatitis B. In unadjusted analyses, FRS was similar between the HCV-infected and
      HCV-uninfected groups [median (interquartile range, IQR) risk points 13 (10-14)
      vs. 13 (10-14), p=0.192]. Cholesterol levels were lower and current smoking more
      prevalent in the HCV groups (both HCV and HIV/HCV) compared with the uninfected
      groups (p<0.001 for both). Prevalence of non-FRS CHD risk factors, such as
      substance abuse and chronic kidney disease, in the cohort was high, and differed
      by HCV and HIV status. Adjusting for age, race/ethnicity, body mass index,
      chronic kidney disease, drug and alcohol use, and HIV status, HCV infection was
      associated with minimally lower FRS (beta=-0.095 risk points, p<0.001),
      suggesting a small but significant difference in 10-year CHD risk estimation in
      HCV-infected as compared to HCV-uninfected persons when measuring risk by FRS.
      Given the complex relationship between HCV, HIV, and CHD risk factors, some of
      which are not captured by the FRS, the FRS may underestimate CHD risk in HCV
      monoinfected and HIV/HCV-coinfected persons. HCV- and HIV/HCV-specific risk
      scores may be needed to optimize CHD risk stratification.

PMID- 25858665
TI  - Profiles and technological requirements of urogenital probiotics.
AB  - Probiotics, defined as live microorganisms that, when administered in adequate
      amounts, confer a health benefit on the host, are considered a valid and novel
      alternative for the prevention and treatment of female urogenital tract
      infections. Lactobacilli, the predominant microorganisms of the healthy human
      vaginal microbiome, can be included as active pharmaceutical ingredients in
      probiotics products. Several requirements must be considered or criteria
      fulfilled during the development of a probiotic product or formula for the female
      urogenital tract. This review deals with the main selection criteria for
      urogenital probiotic microorganisms: host specificity, potential beneficial
      properties, functional specifications, technological characteristics and clinical
      trials used to test their effect on certain physiological and pathological
      conditions. Further studies are required to complement the current knowledge and
      support the clinical applications of probiotics in the urogenital tract. This
      therapy will allow the restoration of the ecological equilibrium of the
      urogenital tract microbiome as well as the recovery of the sexual and
      reproductive health of women. 

PMID- 25858666
TI  - Recent advances on anti-HIV vaginal delivery systems development.
AB  - A review of the recent outcomes regarding technologies to prevent vaginal
      transmission of HIV, mainly by using antiretroviral (ARV) drugs formulated as
      microbicides. An introduction about the HIV transmission mechanisms by the
      vaginal route is included, together with the recent challenges faced for
      development of successful microbicide products. The outcomes of clinical
      evaluations are mentioned, and the different formulation strategies studied to
      date, with the requirements, advantages, disadvantages and limitations of each
      dosage-form type, are presented. Finally, the recent attempts to apply various
      types of nanotechnologies in order to develop advanced microbicide-products and
      overcome existing limitations, are discussed. 

PMID- 25858664
TI  - Particle tracking in drug and gene delivery research: State-of-the-art
      applications and methods.
AB  - Particle tracking is a powerful microscopy technique to quantify the motion of
      individual particles at high spatial and temporal resolution in complex fluids
      and biological specimens. Particle tracking's applications and impact in drug and
      gene delivery research have greatly increased during the last decade. Thanks to
      advances in hardware and software, this technique is now more accessible than
      ever, and can be reliably automated to enable rapid processing of large data
      sets, thereby further enhancing the role that particle tracking will play in drug
      and gene delivery studies in the future. We begin this review by discussing
      particle tracking-based advances in characterizing extracellular and cellular
      barriers to therapeutic nanoparticles and in characterizing nanoparticle size and
      stability. To facilitate wider adoption of the technique, we then present a user
      friendly review of state-of-the-art automated particle tracking algorithms and
      methods of analysis. We conclude by reviewing technological developments for next
      generation particle tracking methods, and we survey future research directions in
      drug and gene delivery where particle tracking may be useful. 

PMID- 25858667
TI  - Conflicting relationship between platelets and prognosis of hepatocellular
      carcinoma: is platelet-derived serotonin involved in?

PMID- 25858669
TI  - Optical control of biological processes by light-switchable proteins.
AB  - Cellular processes such as proliferation, differentiation, or migration depend on
      precise spatiotemporal coordination of protein activities. Correspondingly,
      reaching a quantitative understanding of cellular behavior requires experimental
      approaches that enable spatial and temporal modulation of protein activity.
      Recently, a variety of light-sensitive protein domains have been engineered as
      optogenetic actuators to spatiotemporally control protein activity. In the
      present review, we discuss the principle of these optical control methods and
      examples of their applications in modulating signaling pathways. By controlling
      protein activity with spatiotemporal specificity, tunable dynamics, and
      quantitative control, light-controllable proteins promise to accelerate our
      understanding of cellular and organismal biology.

PMID- 25858670
TI  - Three-dimensional printing of high-content graphene scaffolds for electronic and
      biomedical applications.
AB  - The exceptional properties of graphene enable applications in electronics,
      optoelectronics, energy storage, and structural composites. Here we demonstrate a
      3D printable graphene (3DG) composite consisting of majority graphene and
      minority polylactide-co-glycolide, a biocompatible elastomer, 3D-printed from a
      liquid ink. This ink can be utilized under ambient conditions via extrusion-based
      3D printing to create graphene structures with features as small as 100 MUm
      composed of as few as two layers (<300 MUm thick object) or many hundreds of
      layers (>10 cm thick object). The resulting 3DG material is mechanically robust
      and flexible while retaining electrical conductivities greater than 800 S/m, an
      order of magnitude increase over previously reported 3D-printed carbon materials.
      In vitro experiments in simple growth medium, in the absence of neurogenic
      stimuli, reveal that 3DG supports human mesenchymal stem cell (hMSC) adhesion,
      viability, proliferation, and neurogenic differentiation with significant
      upregulation of glial and neuronal genes. This coincides with hMSCs adopting
      highly elongated morphologies with features similar to axons and presynaptic
      terminals. In vivo experiments indicate that 3DG has promising biocompatibility
      over the course of at least 30 days. Surgical tests using a human cadaver nerve
      model also illustrate that 3DG has exceptional handling characteristics and can
      be intraoperatively manipulated and applied to fine surgical procedures. With
      this unique set of properties, combined with ease of fabrication, 3DG could be
      applied toward the design and fabrication of a wide range of functional
      electronic, biological, and bioelectronic medical and nonmedical devices. 

PMID- 25858668
TI  - Deciphering principles of morphogenesis from temporal and spatial patterns on the
      integument.
AB  - BACKGROUND: How tissue patterns form in development and regeneration is a
      fundamental issue remaining to be fully understood. The integument often forms
      repetitive units in space (periodic patterning) and time (cyclic renewal), such
      as feathers and hairs. Integument patterns are visible and experimentally
      manipulatable, helping us reveal pattern formative processes. Variability is seen
      in regional phenotypic specificities and temporal cycling at different
      physiological stages. RESULTS: Here we show some cellular/molecular bases
      revealed by analyzing integument patterns. (1) Localized cellular activity
      (proliferation, rearrangement, apoptosis, differentiation) transforms prototypic
      organ primordia into specific shapes. Combinatorial positioning of different
      localized activity zones generates diverse and complex organ forms. (2)
      Competitive equilibrium between activators and inhibitors regulates stem cells
      through cyclic quiescence and activation. CONCLUSIONS: Dynamic interactions
      between stem cells and their adjacent niche regulate regenerative behavior,
      modulated by multi-layers of macro-environmental factors (dermis, body hormone
      status, and external environment). Genomics studies may reveal how positional
      information of localized cellular activity is stored. In vivo skin imaging and
      lineage tracing unveils new insights into stem cell plasticity. Principles of
      self-assembly obtained from the integumentary organ model can be applied to help
      restore damaged patterns during regenerative wound healing and for tissue
      engineering to rebuild tissues. Developmental Dynamics 244:905-920, 2015. (c)
      2015 Wiley Periodicals, Inc.

PMID- 25858673
TI  - Quantifying aromaticity with electron delocalisation measures.
AB  - Aromaticity cannot be measured directly by any physical or chemical experiment
      because it is not a well-defined magnitude. Its quantification is done indirectly
      from the measure of different properties that are usually found in aromatic
      compounds such as bond length equalisation, energetic stabilisation, and
      particular magnetic behaviour associated with induced ring currents. These
      properties have been used to set up the myriad of structural-, energetic-, and
      magnetic-based indices of aromaticity known to date. The cyclic delocalisation of
      mobile electrons in two or three dimensions is probably one of the key aspects
      that characterise aromatic compounds. However, it has not been until the last
      decade that electron delocalisation measures have been widely employed to
      quantify aromaticity. Some of these new indicators of aromaticity such as the
      PDI, FLU, ING, and INB were defined in our group. In this paper, we review the
      different existing descriptors of aromaticity that are based on electron
      delocalisation properties, we compare their performance with indices based on
      other properties, and we summarise a number of applications of electronic-based
      indices for the analysis of aromaticity in interesting chemical problems. 

PMID- 25858671
TI  - Galectin-1-secreting neural stem cells elicit long-term neuroprotection against
      ischemic brain injury.
AB  - Galectin-1 (gal-1), a special lectin with high affinity to beta-galactosides, is
      implicated in protection against ischemic brain injury. The present study
      investigated transplantation of gal-1-secreting neural stem cell (s-NSC) into
      ischemic brains and identified the mechanisms underlying protection. To
      accomplish this goal, secretory gal-1 was stably overexpressed in NE-4C neural
      stem cells. Transient cerebral ischemia was induced in mice by middle cerebral
      artery occlusion for 60 minutes and s-NSCs were injected into the striatum and
      cortex within 2 hours post-ischemia. Brain infarct volume and neurological
      performance were assessed up to 28 days post-ischemia. s-NSC transplantation
      reduced infarct volume, improved sensorimotor and cognitive functions, and
      provided more robust neuroprotection than non-engineered NSCs or gal-1
      overexpressing (but non-secreting) NSCs. White matter injury was also ameliorated
      in s-NSC-treated stroke mice. Gal-1 modulated microglial function in vitro, by
      attenuating secretion of pro-inflammatory cytokines (TNF-alpha and nitric oxide)
      in response to LPS stimulation and enhancing production of anti-inflammatory
      cytokines (IL-10 and TGF-beta). Gal-1 also shifted microglia/macrophage
      polarization toward the beneficial M2 phenotype in vivo by reducing CD16
      expression and increasing CD206 expression. In sum, s-NSC transplantation confers
      robust neuroprotection against cerebral ischemia, probably by alleviating white
      matter injury and modulating microglial/macrophage function. 

PMID- 25858674
TI  - Salidroside prevents cognitive impairment induced by chronic cerebral
      hypoperfusion in rats.
AB  - OBJECTIVE: To investigate the effects of salidroside on cognitive dysfunction
      induced by chronic cerebral hypoperfusion in rats. METHODS: Male Sprague-Dawley
      rats (n = 36) were divided into three groups (n = 12 per group): sham operation;
      bilateral permanent occlusion of the common carotid arteries (2-VO); 2-VO +
      salidroside. Rats received 20 mg/kg per day salidroside or vehicle
      intraperitoneal injection beginning the day before surgery and continuing until
      34 days postoperatively. Cognitive function was evaluated by Morris water maze
      test and hippocampal long-term potentiation (LTP) measurement. Hippocampal
      neuronal apoptosis was evaluated via immunofluorescence. RESULTS: Chronic
      cerebral hypoperfusion caused marked cognitive deficit and LTP inhibition. These
      effects were largely ameliorated by salidroside administration. Salidroside
      prevented caspase-3 activation, increased the ratio of Bax/Bcl-2, and reversed
      hippocampal neuronal loss induced by chronic cerebral hypoperfusion. CONCLUSIONS:
      Salidroside prevents cognitive deficits caused by chronic cerebral hypoperfusion
      in rats, and alleviates apoptosis in the hippocampal CA1 area.

PMID- 25858676
TI  - The SCL/TAL1 Transcription Factor Represses the Stress Protein DDiT4/REDD1 in
      Human Hematopoietic Stem/Progenitor Cells.
AB  - Hematopoietic stem/progenitor cells (HSPCs) are regulated through numerous
      molecular mechanisms that have not been interconnected. The transcription factor
      stem cell leukemia/T-cell acute leukemia 1 (TAL1) controls human HSPC but its
      mechanism of action is not clarified. In this study, we show that knockdown (KD)
      or short-term conditional over-expression (OE) of TAL1 in human HSPC ex vivo,
      respectively, blocks and maintains hematopoietic potentials, affecting
      proliferation of human HSPC. Comparative gene expression analyses of TAL1/KD and
      TAL1/OE human HSPC revealed modifications of cell cycle regulators as well as
      previously described TAL1 target genes. Interestingly an inverse correlation
      between TAL1 and DNA damage-induced transcript 4 (DDiT4/REDD1), an inhibitor of
      the mammalian target of rapamycin (mTOR) pathway, is uncovered. Low
      phosphorylation levels of mTOR target proteins in TAL1/KD HSPC confirmed an
      interplay between mTOR pathway and TAL1 in correlation with TAL1-mediated effects
      of HSPC proliferation. Finally chromatin immunoprecipitation experiments
      performed in human HSPC showed that DDiT4 is a direct TAL1 target gene.
      Functional analyses showed that TAL1 represses DDiT4 expression in HSPCs. These
      results pinpoint DDiT4/REDD1 as a novel target gene regulated by TAL1 in human
      HSPC and establish for the first time a link between TAL1 and the mTOR pathway in
      human early hematopoietic cells. Stem Cells 2015;33:2268-2279. 

PMID- 25858675
TI  - Controlled induction of DNA double-strand breaks in the mouse liver induces
      features of tissue ageing.
AB  - DNA damage has been implicated in ageing, but direct evidence for a causal
      relationship is lacking, owing to the difficulty of inducing defined DNA lesions
      in cells and tissues without simultaneously damaging other biomolecules and
      cellular structures. Here we directly test whether highly toxic DNA double-strand
      breaks (DSBs) alone can drive an ageing phenotype using an adenovirus-based
      system based on tetracycline-controlled expression of the SacI restriction
      enzyme. We deliver the adenovirus to mice and compare molecular and cellular end
      points in the liver with normally aged animals. Treated, 3-month-old mice display
      many, but not all signs of normal liver ageing as early as 1 month after
      treatment, including ageing pathologies, markers of senescence, fused
      mitochondria and alterations in gene expression profiles. These results, showing
      that DSBs alone can cause distinct ageing phenotypes in mouse liver, provide new
      insights in the role of DNA damage as a driver of tissue ageing. 

PMID- 25858677
TI  - Pharmacy claims data versus patient self-report to measure contraceptive method
      continuation.
AB  - OBJECTIVE: To compare self-reported 12-month continuation of oral contraceptive
      pills (OCPs), patch, and ring versus continuation by pharmacy claims data. STUDY
      DESIGN: Women in the Contraceptive CHOICE Project who chose OCPs, the patch, or
      the ring as their initial method were included. Continuation was assessed by
      periodic telephone survey and by obtaining prescription claims data. Continuation
      was defined as no gap of more than 30 days. Kaplan-Meier survival functions were
      used to estimate continuation rates and cumulative unintended pregnancy rates.
      Kappa statistic assessed the level of agreement between self-report and claims
      data. RESULTS: We analyzed 1510 women who initiated use by 3 months and provided
      information on discontinuation. Of OCP users, 59% continued their method at 12
      months by self-report versus 38% by pharmacy claims. Patch and ring users had
      self-reported/pharmacy continuation of 45%/28% and 57%/37%, respectively. Kappa
      coefficients and their 95% confidence intervals between the two measurements were
      0.46 (0.40, 0.52), 0.54 (0.39, 0.68), and 0.54 (0.47, 0.61) for OCP, patch, and
      ring, respectively. Among women who self-reported continuation, unintended
      pregnancy rates were 0.4% in those who continued by pharmacy claims versus 4.9%
      in those who discontinued according to claims data. CONCLUSION: Contraceptive
      continuation rates differ by self-report versus pharmacy claims with women
      overestimating their continuation by self-report. IMPLICATIONS: This article
      directly compares contraception continuation rates by self-report and by pharmacy
      claims data. The study suggests that previously reported continuation rates from
      survey data overestimate specific method use.

PMID- 25858678
TI  - Abnormally elevated serum hCG in a patient with end-stage renal disease seeking
      abortion: to be expected or a cause for concern? A case report.
AB  - A patient with end-stage renal disease on hemodialysis was referred to our
      abortion clinic with a concern for molar pregnancy. By 12 weeks, her human
      chorionic gonadotropin (hCG) level was over 500,000. A review of the literature
      demonstrates that elevated hCG should be expected in this population and should
      not alter care. 

PMID- 25858679
TI  - Molecular genetic analysis of para-Bombay phenotype in Chinese persons: a novel
      FUT1 allele is identified.

PMID- 25858680
TI  - [Botulism outbreak in Castellon (Spain)].

PMID- 25858681
TI  - Comparison of the CT OligoGen kit with cobas 4800 assay for detection of
      Chlamydia trachomatis.
AB  - INTRODUCTION: A prospective study was designed to assess the performance of the
      new CT OligoGen kit and the cobas 4800 assay for detection of Chlamydia
      trachomatis. METHODS: A set of samples that included urine samples (n=212),
      endocervical (n=167), rectal (n=53), pharyngeal (n=7) and urethral swabs (n=3).
      The samples were sent from a regional sexually transmitted diseases (STD) clinic
      in Seville, Spain, and were collected from 261 men and 181 women. Discordant
      results were re-analyzed and clinical data and other tests were reviewed in order
      to resolve them. RESULTS: Sensitivity, specificity, positive predicative value
      (PPV), negative predictive value (NPV) and kappa value for C. trachomatis
      detection using the CT OligoGen kit were 98.5%, 100%, 100%, 95.4% and 0.97,
      respectively. CONCLUSIONS: This new kit had a high sensitivity, specificity, PPV
      and NPV for C. trachomatis, therefore the performance profile confirms the
      usefulness and reliable results of this new assay.

PMID- 25858682
TI  - Direct medical costs and source of cost differences across the spectrum of
      cognitive decline: a population-based study.
AB  - BACKGROUND: Objective cost estimates and source of cost differences are needed
      across the spectrum of cognition, including cognitively normal (CN), mild
      cognitive impairment (MCI), newly discovered dementia, and prevalent dementia.
      METHODS: Subjects were a subset of the Mayo Clinic Study of Aging stratified
      random sampling of Olmsted County, MN, residents aged 70 to 89 years. A
      neurologist reviewed provider-linked medical records to identify prevalent
      dementia (review date = index). Remaining subjects were invited to participate in
      prospective clinical/neuropsychological assessments; participants were
      categorized as CN, MCI, or newly discovered dementia (assessment date = index).
      Costs for medical services/procedures 1-year pre-index (excluding indirect and
      long-term care costs) were estimated using line-item provider-linked
      administrative data. We estimated contributions of care-delivery site and
      comorbid conditions (including and excluding neuropsychiatric diagnoses) to
      between-category cost differences. RESULTS: Annual mean medical costs for CN,
      MCI, newly discovered dementia, and prevalent dementia were $6042, $6784, $9431,
      $11,678, respectively. Hospital inpatient costs contributed 70% of total costs
      for prevalent dementia and accounted for differences between CN and both
      prevalent and newly discovered dementia. Ambulatory costs accounted for
      differences between CN and MCI. Age-, sex-, education-adjusted differences
      reached significance for CN versus newly discovered and prevalent dementia and
      for MCI versus prevalent dementia. After considering all comorbid diagnoses,
      between-category differences were reduced (e.g., prevalent dementia minus MCI
      (from $4842 to $3575); newly discovered dementia minus CN (from $3578 to $711)).
      Following the exclusion of neuropsychiatric diagnoses from comorbidity
      adjustment, between-category differences tended to revert to greater differences.
      CONCLUSIONS: Cost estimates did not differ significantly between CN and MCI.
      Substantial differences between MCI and prevalent dementia reflected high
      inpatient costs for dementia and appear partly related to co-occurring mental
      disorders. Such comparisons can help inform models aimed at identifying where,
      when, and for which individuals proposed interventions might be cost-effective.

PMID- 25858683
TI  - Performance of the CogState computerized battery in the Mayo Clinic Study on
      Aging.
AB  - INTRODUCTION: The feasibility and validity of brief computerized cognitive
      batteries at the population-level are unknown. METHODS: Nondemented participants
      (n = 1660, age 50-97 years) in the Mayo Clinic Study on Aging completed the
      computerized CogState battery and standard neuropsychological battery. The
      correlation between tests was examined and comparisons between CogState
      performance on the personal computer (PC) and iPad (n = 331), and in the clinic
      vs. at home (n = 194), were assessed. RESULTS: We obtained valid data on greater
      than 97% of participants on each test. Correlations between the CogState and
      neuropsychological tests ranged from -0.462 to 0.531. Although absolute
      differences between the PC and iPad were small and participants preferred the
      iPad, performance on the PC was faster. Participants performed faster on
      Detection, One Card Learning, and One Back at home compared with the clinic.
      DISCUSSION: The computerized CogState battery, especially the iPad, was feasible,
      acceptable, and valid in the population.

PMID- 25858684
TI  - Perinatal depression screening in a Women, Infants, and Children (WIC) program:
      perception of feasibility and acceptability among a multidisciplinary staff.
AB  - OBJECTIVE: Best practices for addressing women's mental health and screening for
      depression in public health clinics are not available. Clinic staff are often
      responsible for screening for depression; however, few studies examine staff
      perceptions on feasibility and acceptability of using perinatal screening for
      mood disorders in ethnically diverse public health clinics. METHODS: During
      December 2012, we conducted four focus groups using a semistructured interview
      guide with public health clinic staff of varying disciplines (n=25) in a Special
      Supplemental Nutrition Program for Women, Infants, and Children. All interviews
      were audio recorded and analyzed using thematic analysis. RESULTS: We found five
      descriptive themes related to acceptability and feasibility of screening for
      perinatal depression in a public health clinic. The main themes include (1)
      literacy barriers, (2) need for referrals and follow-up with outside services,
      (3) training and capacity needs, (4) stigma of depression, and (5) location and
      privacy of screening. Although multiple barriers to universal depression
      screening in a public health clinic were identified, participants found value in
      practice of screening low-income women for depression. CONCLUSION: Factors for
      facilitating implementation of systematic depression screening in a public health
      clinic have been identified. Implications discuss how policy makers and public
      health clinic administrators can improve the universal depression screening
      process.

PMID- 25858685
TI  - Rechallenging 5-Fluorouracil in a Patient With Capecitabine-Induced Ventricular
      Fibrillation.

PMID- 25858686
TI  - Th2 cytokines impair innate immune responses to rhinovirus in respiratory
      epithelial cells.
AB  - BACKGROUND: Asthma and other Th2 inflammatory conditions have been associated
      with increased susceptibility to viral infections. The mechanisms by which Th2
      cytokines can influence immune responses to infections are largely unknown.
      METHODS: We measured the effects of Th2 cytokines (IL-4 and IL-13) on bronchial
      epithelial cell innate immune antiviral responses by assessing interferon (IFN
      beta and IFN-lambda1) induction following rhinovirus (RV)-16 infection. We also
      investigated the modulatory effects of Th2 cytokines on Toll-like receptor 3
      (TLR3), interferon-responsive factor 3 (IRF3) and nuclear factor (NF)-kB, that is
      key molecules and transcription factors involved in the rhinovirus-induced
      interferon production and inflammatory cascade. Pharmacological and redox
      modulation of these pathways was also assessed. RESULTS: Th2 cytokines impaired
      RV-16-induced interferon production, increased rhinovirus replication and
      impaired TLR3 expression in bronchial epithelial cells. These results were
      replicated in vivo: we found increased IL-4 mRNA levels in nasal epithelial cells
      from nasal brushing of atopic rhinitis patients and a parallel reduction in TLR3
      expression and increased RV-16 replication compared to nonatopic subjects.
      Mechanistically, Th2 cytokines impaired RV-16-induced activation of IRF3, but had
      no effects on RV-16-induced NF-kB activation in bronchial epithelial cell
      cultures. N-acetylcysteine and phosphoinositide 3-kinase (PI3K) inhibitor
      restored the inhibitory effects of Th2 cytokines over RV-16-induced activation of
      IRF3. CONCLUSIONS: IL-4 and IL-13, through inhibition of TLR3 expression and
      signalling (IRF3), impair immune response to RV-16 infection. These data suggest
      that Th2 conditions increase susceptibility to infections and identify
      pharmacological approaches with potential to restore impaired immune response in
      these conditions.

PMID- 25858688
TI  - Optimization of hydrogen-evolving photochemical molecular devices.
AB  - A molecular photocatalyst consisting of a Ru(II) photocenter, a
      tetrapyridophenazine bridging ligand, and a PtX2 (X=Cl or I) moiety as the
      catalytic center functions as a stable system for light-driven hydrogen
      production. The catalytic activity of this photochemical molecular device (PMD)
      is significantly enhanced by exchanging the terminal chlorides at the Pt center
      for iodide ligands. Ultrafast transient absorption spectroscopy shows that the
      intramolecular photophysics are not affected by this change. Additionally, the
      general catalytic behavior, that is, instant hydrogen formation, a constant
      turnover frequency, and stability are maintained. Unlike as observed for the Pd
      analogue, the presence of excess halide does not affect the hydrogen generation
      capacity of the PMD. The highly improved catalytic efficiency is explained by an
      increased electron density at the Pt catalytic center, this is confirmed by DFT
      studies. 

PMID- 25858687
TI  - Lentinan exerts synergistic apoptotic effects with paclitaxel in A549 cells via
      activating ROS-TXNIP-NLRP3 inflammasome.
AB  - Paclitaxel is generally used to treat cancers in clinic as an inhibitor of cell
      division. However, the acquired resistance in tumours limits its clinical
      efficacy. Therefore, the aim of this study was to detect whether co-treatment
      with lentinan enhanced the anti-cancer effects of paclitaxel in A549 cells. We
      found that the combination of paclitaxel and lentinan resulted in a significantly
      stronger inhibition on A549 cell proliferation than paclitaxel treatment alone.
      Co-treatment with paclitaxel and lentinan enhanced cell apoptosis rate by
      inducing caspase-3 activation. Furthermore, co-treatment with paclitaxel and
      lentinan significantly triggered reactive oxygen species (ROS) production, and
      increased thioredoxin-interacting protein (TXNIP) expression. Moreover, co
      treatment with paclitaxel and lentinan enhanced TXNIP-NLRP3 interaction, and
      activated NLRP3 inflammasome whereat interleukin-1beta levels were increased and
      cell apoptosis was induced. In addition, combination of paclitaxel and lentinan
      could activate apoptosis signal regulating kinase-1 (ASK1)/p38 mitogen-activated
      protein kinase (MAPK) signal which also contributed to cell apoptosis. Taken
      together, co-treatment with paclitaxel and lentinan exerts synergistic apoptotic
      effects in A549 cells through inducing ROS production, and activating NLRP3
      inflammasome and ASK1/p38 MAPK signal pathway. 

PMID- 25858690
TI  - High-quality phosphorus-doped MoS2 ultrathin nanosheets with amenable ORR
      catalytic activity.
AB  - Engineering phosphorus heteroatoms into the plane of ultrathin MoS2 nanosheets is
      realized via a facile thermolytical process. The doping of low-electronegative P
      atoms generates an extra ORR activity with four-electron selectivity, manifesting
      seven-fold current increase as well as 160 mV positive shift in both onset and
      half-wave potentials. 

PMID- 25858689
TI  - Consumption of whole grains and cereal fiber and total and cause-specific
      mortality: prospective analysis of 367,442 individuals.
AB  - BACKGROUND: Intakes of whole grains and cereal fiber have been inversely
      associated with the risk of chronic diseases; however, their relation with total
      and disease-specific mortality remain unclear. We aimed to prospectively assess
      the association of whole grains and cereal fiber intake with all causes and cause
      specific mortality. METHODS: The study included 367,442 participants from the
      prospective NIH-AARP Diet and Health Study (enrolled in 1995 and followed through
      2009). Participants with cancer, heart disease, stroke, diabetes, and self
      reported end-stage renal disease at baseline were excluded. RESULTS: Over an
      average of 14 years of follow-up, a total of 46,067 deaths were documented.
      Consumption of whole grains were inversely associated with risk of all-cause
      mortality and death from cancer, cardiovascular disease (CVD), diabetes,
      respiratory disease, infections, and other causes. In multivariable models, as
      compared with individuals with the lowest intakes, those in the highest intake of
      whole grains had a 17% (95% CI, 14-19%) lower risk of all-cause mortality and 11
      48% lower risk of disease-specific mortality (all P for trend <0.023); those in
      the highest intake of cereal fiber had a 19% (95% CI, 16-21%) lower risk of all
      cause mortality and 15-34% lower risk of disease-specific mortality (all P for
      trend <0.005). When cereal fiber was further adjusted, the associations of whole
      grains with death from CVD, respiratory disease and infections became not
      significant; the associations with all-cause mortality and death from cancer and
      diabetes were attenuated but remained significant (P for trend <0.029).
      CONCLUSIONS: Consumption of whole grains and cereal fiber was inversely
      associated with reduced total and cause-specific mortality. Our data suggest
      cereal fiber is one potentially protective component.

PMID- 25858691
TI  - Development of a bundle measure for preventive service delivery to infants in
      primary care.
AB  - RATIONALE, AIMS AND OBJECTIVES: In the United States, paediatric patients receive
      only 41% of indicated preventive services. Past improvement efforts have not
      bundled preventive services to measure the reliability with which infants'
      physical, developmental and emotional needs are all addressed. We aimed to create
      a comprehensive bundle measure that reflects reliable delivery of preventive
      services during primary care visits, as well as overall preventive service status
      of a population of patients served by three primary care centres. METHOD: Data
      were collected from electronic health records for cohorts of infants < 14 months
      old with at least one visit to one of three primary care centres. Immunizations,
      lead screening, developmental screening and screening for biopsychosocial risk
      factors (gestational age, parental depression, food insecurity) were chosen by
      local expert consensus for inclusion in the preventive services bundle measure.
      Monthly measures of preventive service status at 14 months of age were
      constructed. A visit-level bundle measure of preventive service delivery was also
      created. To obtain a baseline for improvement work, bundle completion rates were
      calculated for infants born in May 2011. Visit-level performance was measured for
      visits from July to August 2012. RESULTS: Among 278 patients born in May 2011,
      22% of patients received the entire bundle of preventive services by 14 months of
      age. On a visit level, patients received all indicated services at 58% of visits.
      CONCLUSION: A novel bundle measure can be used to characterize delivery of
      preventive services and drive improvement at both an individual visit level and a
      population level.

PMID- 25858692
TI  - Variation in reward quality and pollinator attraction: the consumer does not
      always get it right.
AB  - Nearly all bees rely on pollen as the sole protein source for the development of
      their larvae. The central importance of pollen for the bee life cycle should
      exert strong selection on their ability to locate the most rewarding sources of
      pollen. Despite this importance, very few studies have examined the influence of
      intraspecific variation in pollen rewards on the foraging decisions of bees.
      Previous studies have demonstrated that inbreeding reduces viability and hence
      protein content in Mimulus guttatus (seep monkeyflower) pollen and that bees
      strongly discriminate against inbred in favour of outbred plants. We examined
      whether variation in pollen viability could explain this preference using a
      series of choice tests with living plants, artificial plants and olfactometer
      tests using the bumble bee Bombus impatiens. We found that B. impatiens preferred
      to visit artificial plants provisioned with fertile anthers over those
      provisioned with sterile anthers. They also preferred fertile anthers when
      provided only olfactory cues. These bumble bees were unable to discriminate among
      live plants from subpopulations differing dramatically in pollen viability,
      however. They preferred outbred plants even when those plants were from
      subpopulations with pollen viability as low as the inbred populations. Their
      preference for outbred plants was evident even when only olfactory cues were
      available. Our data showed that bumble bees are able to differentiate between
      anthers that provide higher rewards when cues are isolated from the rest of the
      flower. When confronted with cues from the entire flower, their choices are
      independent of the quality of the pollen reward, suggesting that they are
      responding more strongly to cues unassociated with rewards than to those
      correlated with rewards. If so, this suggests that a sensory bias or some level
      of deception may be involved with advertisement to pollinators in M. guttatus. 

PMID- 25858693
TI  - Minimally invasive interventions for replacing missing teeth with implants:
      current status and future perspective.

PMID- 25858694
TI  - [Catatonia].
AB  - In the new classification of the DSM-V, catatonia is individualized as a disease
      of its own. It is defined by presence of at least two out of five criteria: motor
      immobility, negativism, echolalia or echopraxia, sterile motor activity, atypical
      movements. The priority is to look first for organic causes: the main ones are
      neurologic disorders. Intoxication may also be found (illegal drugs or
      medication), and the role of neuroleptic malignant syndrome in catatonia remains
      unclear. Among the psychiatric causes, first come bipolar disorders, especially
      mania; then schizophrenia. Idiopathic forms can also be observed. Epidemiological
      work on catatonia show highly variable results, highlighting a possible
      underestimation of the diagnosis. Among the differential diagnoses, which are
      rare motor syndromes, neuroleptic malignant syndrome and serotonin syndrome are
      also discussed. The diagnosis of catatonia is clinical and can be obtained using
      standardized diagnostic scales. The use of zolpidem provides both a diagnostic
      and therapeutic guidance for the degree of response to drug treatment. The
      physiopathological hypotheses describe an intracerebral GABAergic, dopaminergic
      and glutamatergic dysfunction in catatonic patients. The complete mechanisms are
      still partly unknown. Benzodiazepines are the first treatment of choice.
      Electroconvulsive therapy is used secondarily or in severe cases. First
      generation antipsychotics are prohibited, at the risk of worsening the catatonia
      in becoming malignant and lethal. The renewed interest in the catatonic syndrome
      during the past recent years has expanded research on the mechanisms of this
      syndrome and opened the way to new therapeutic options. The latest works tend to
      modulate the strict prohibition of antipsychotic in a catatonic patient. 

PMID- 25858695
TI  - Sport science for salmon and other species: ecological consequences of metabolic
      power constraints.
AB  - For metabolically demanding behaviours, power supply (ATP resynthesis per unit
      time) is an important constraint on performance. Yet ecology as a discipline
      lacks a framework to account for these power constraints. We developed such a
      framework (borrowing concepts from sports science) and applied it to the upriver
      migration of anadromous fish. Our models demonstrate how metabolic power
      constraints alters optimal migratory behaviour; in response to strong counter
      flows, fish minimise cost of transport by alternating between rapid,
      anaerobically fuelled swimming and holding to restore spent fuels. Models
      ignoring power constraints underestimated the effect of elevated water
      temperature on migration speed and costs (by up to 60%). These differences were
      primarily due to a temperature-mediated reduction in aerobic scope that impairs
      the ability of fish to rapidly migrate through warm waters. Our framework
      provides a mechanistic link between temperature-induced reductions in aerobic
      scope and their ecological consequences for individuals, populations and
      communities. 

PMID- 25858696
TI  - Loss of ASRGL1 expression is an independent biomarker for disease-specific
      survival in endometrioid endometrial carcinoma.
AB  - OBJECTIVE: For endometrial carcinoma, prognostic stratification methods do not
      satisfactorily identify patients with adverse outcome. Currently, histology,
      tumor grade and stage are used to tailoring surgical treatment and to determine
      the need for adjuvant treatment. Low-risk patients are not considered to require
      adjuvant therapy or staging lymphadenectomy. For patients with intermediate or
      high risk, some guidelines recommend tailoring adjuvant treatment according to
      additional negative prognostic factors. Our objective was to evaluate the
      biomarker potential of the ASRGL1 protein in endometrial carcinoma. METHODS:
      Using The Human Protein Atlas (www.proteinatlas.org), the l-asparaginase (ASRGL1)
      protein was identified as an endometrial carcinoma biomarker candidate. ASRGL1
      expression was immunohistochemically evaluated with an extensively validated
      antibody on two independent endometrial carcinoma cohorts (n=229 and n=286)
      arranged as tissue microarrays. Staining results were correlated with clinical
      features. RESULTS: Reduced expression of ASRGL1, defined as <75% positively
      stained tumor cells, was significantly associated with poor prognosis and reduced
      disease-specific survival in endometrioid endometrial adenocarcinoma (EEA). In
      multivariate analysis the hazard ratios for disease-specific survival were 3.55
      (95% CI=1.10-11.43; p=0.003) and 3.23 (95% CI=1.53-6.81; p=0.002) in the two
      cohorts, respectively. Of the 48 cases with Grade 3 Stage I tumor all disease
      related deaths were associated with low ASRGL1 expression. CONCLUSIONS: Loss of
      ASRGL1 in EEA is a powerful biomarker for poor prognosis and retained ASRGL1 has
      a positive impact on survival. ASRGL1 immunohistochemistry has potential to
      become an additional tool for prognostication in cases where tailoring adjuvant
      treatment according to additional prognostic factors besides grade and stage is
      recommended.

PMID- 25858697
TI  - Melatonin ameliorates amyloid beta-induced memory deficits, tau
      hyperphosphorylation and neurodegeneration via PI3/Akt/GSk3beta pathway in the
      mouse hippocampus.
AB  - Alzheimer's disease (AD) is the most prevalent age-related neurodegenerative
      disease, pathologically characterized by the accumulation of amyloid beta (Abeta)
      aggregation in the brain, and is considered to be the primary cause of cognitive
      dysfunction. Abeta aggregates lead to synaptic disorder, tau
      hyperphosphorylation, and neurodegeneration. In this study, the underlying
      neuroprotective mechanism of melatonin against Abeta1-42-induced neurotoxicity
      was investigated in the mice hippocampus. Intracerebroventricular (i.c.v.) Abeta1
      42-injection triggered memory impairment, synaptic disorder, hyperphosphorylation
      of tau protein, and neurodegeneration in the mice hippocampus. After 24 hr of
      Abeta1-42 injection, the mice were treated with melatonin (10 mg/kg,
      intraperitonially) for 3 wks, reversed the Abeta1-42-induced synaptic disorder
      via increasing the level of presyanptic (Synaptophysin and SNAP-25) and
      postsynaptic protein [PSD95, p-GluR1 (Ser845), SNAP23, and p-CREB (Ser133)],
      respectively, and attenuated the Abeta1-42-induced memory impairment. Chronic
      melatonin treatment attenuated the hyperphosphorylation of tau protein via
      PI3K/Akt/GSK3beta signaling by activating the p-PI3K, p-Akt (Ser 473) and p
      GSK3beta (Ser9) in the Abeta1-42-treated mice. Furthermore, melatonin decreased
      Abeta1-42 -induced apoptosis through decreasing the overexpression of caspase-9,
      caspase-3, and PARP-1 level. Additionally, the evaluation of immunohistochemical
      analysis of caspase-3, Fluorojade-B, and Nissl staining indicated that melatonin
      prevented neurodegeneration in Abeta1-42-treated mice. Our results demonstrated
      that melatonin has neuroprotective effect against Abeta1-42-induced neurotoxicity
      through decreasing memory impairment, synaptic disorder, tau
      hyperphosphorylation, and neurodegeneration via PI3K/Akt/GSK3beta signaling in
      the Abeta1-42-treated mouse model of AD. On the basis of these results, we
      suggest that melatonin could be an effective, promising, and safe neuroprotective
      candidate for the treatment of progressive neurodegenerative disorders, such as
      AD.

PMID- 25858698
TI  - Electrophysiological evidence for the effects of unitization on associative
      recognition memory in older adults.
AB  - Normal aging is associated with greater decline in associative memory relative to
      item memory due to impaired recollection. Familiarity may also contribute to
      associative recognition when stimuli are perceived as a 'unitized'
      representation. Given that familiarity is relatively preserved in older adults,
      we explored whether age-related associative memory deficits could be attenuated
      when associations were unitized (i.e., compounds) compared with those non
      unitized (i.e., unrelated word pairs). Young and older adults performed an
      associative recognition task while electroencephalogram (EEG) was recorded.
      Behavioral results showed that age differences were smaller for recognition of
      compounds than for unrelated word pairs. ERP results indicated that only
      compounds evoked an early frontal old/new effect in older adults. Moreover, the
      early frontal old/new effect was positively correlated with associative
      discrimination accuracy. These findings suggest that reduced age-related
      associative deficits under unitized condition may be associated with the presence
      of familiarity-based retrieval of compounds in older adults. 

PMID- 25858699
TI  - Seasonal variation of non-shivering thermogenesis (NST) during mild cold
      exposure.
AB  - BACKGROUND: The physiological function of non-shivering thermogenesis (NST) has
      been investigated in recent years, and some studies have discussed the importance
      of NST with respect to human cold adaptation. The present study aimed to clarify
      individual and seasonal variations in NST that occurred as a result of mild cold
      exposure. METHODS: Seventeen male university students participated in the present
      study during summer and winter. The climate chamber used was programmed so that
      ambient temperature dropped from 28 degrees C to 16 degrees C over an 80-min
      period. Physiological parameters of test subjects were recorded during the
      experiments. RESULTS: Increases in oxygen intake (VO2) during cold exposure were
      significantly greater without shivering in winter than they were in summer.
      Respiratory exchange ratio (RER) was significantly lower during thermoneutral
      baseline and cold exposure in winter than it was during the same periods in
      summer. In addition, there was a significant negative correlation between
      DeltaVO2 and DeltaRER. CONCLUSIONS: Increase of VO2 without shivering indicated
      increase of NST, and decrease of RER depends on the metabolization of fat in
      winter. These results suggested that NST activity was activated by seasonal
      acclimatization, and individual variation of NST depends on individual variation
      of fat metabolism.

PMID- 25858700
TI  - Arabidopsis uses two gluconeogenic gateways for organic acids to fuel seedling
      establishment.
AB  - Gluconeogenesis is a fundamental metabolic process that allows organisms to make
      sugars from non-carbohydrate stores such as lipids and protein. In eukaryotes
      only one gluconeogenic route has been described from organic acid intermediates
      and this relies on the enzyme phosphoenolpyruvate carboxykinase (PCK). Here we
      show that two routes exist in Arabidopsis, and that the second uses pyruvate,
      orthophosphate dikinase (PPDK). Gluconeogenesis is critical to fuel the
      transition from seed to seedling. Arabidopsis pck1 and ppdk mutants are
      compromised in seed-storage reserve mobilization and seedling establishment.
      Radiolabelling studies show that PCK predominantly allows sugars to be made from
      dicarboxylic acids, which are products of lipid breakdown. However, PPDK also
      allows sugars to be made from pyruvate, which is a major product of protein
      breakdown. We propose that both routes have been evolutionarily conserved in
      plants because, while PCK expends less energy, PPDK is twice as efficient at
      recovering carbon from pyruvate. 

PMID- 25858702
TI  - Microdeletion of the escape genes KDM5C and IQSEC2 in a girl with severe
      intellectual disability and autistic features.
AB  - Intellectual disability (ID) is a very heterogeneous disorder with over 100 ID
      genes located on the X chromosome alone. Of these, KDM5C and IQSEC2 are located
      adjacent to each other at the Xp11.22 locus. While mutations in either of these
      genes are associated with severe ID in males, female carriers are mostly
      unaffected. Here, we report on a female patient with severe ID and autistic
      features carrying a de novo 0.4 Mb deletion containing six coding genes including
      KDM5C and IQSEC2. X-inactivation analysis revealed skewing in a lymphocyte
      derived cell line from this patient with preferential inactivation of the mutant
      X chromosome. As the brain-expressed KDM5C and IQSEC2 genes escape X
      inactivation, deletion of these alleles could still be detrimental despite
      skewing of X-inactivation. Indeed, mutations in either of both genes have been
      reported in a few female ID patients. Expression analysis in the patients' cell
      line revealed decreased KDM5C mRNA levels compared to female controls. IQSEC2
      levels could not be compared due to very low expression in blood. Overall, our
      data suggest that heterozygous loss-of-function of the escape genes KDM5C and/or
      IQSEC2 can contribute to severe ID in female patients and should be taken into
      account in diagnostics. 

PMID- 25858703
TI  - Familial transmission of 5p13.2 duplication due to maternal der(X)ins(X;5).
AB  - Submicroscopic duplications of 5p13 have been recently reported in several cases,
      warranting the description of a new clinical entity (Chromosome 5p13 Duplication
      Syndrome; MIM 613174). These microduplications, while variable in size, all
      contain at least part of the NIPBL gene. Patients with duplications in this
      region present with intellectual disability/developmental delay (ID/DD) and
      dysmorphic facies. In addition, skeletal and brain abnormalities have been
      variably reported, as well as propensity for obesity in adulthood and hypotonia.
      We report a family with two affected sons and two affected daughters, each
      carrying a duplication at 5p13.2 encompassing the 3' portion of SLC1A3 and the 5'
      portion of NIPBL. Upon confirming the SNP microarray finding by FISH in the
      proband, it was discovered that the 5p13.2 duplication was located on the short
      arm of the X chromosome. Further FISH studies on the family demonstrated that all
      affected children and their mother carried a derivative X chromosome with
      insertion of material from 5p13.2 into the intermediate region of Xp
      [der(X)ins(X;5)(p2?2.1;p13.2p13.2)]. To our knowledge, this is the first report
      of an inherited duplication of 5p13.2 with multiple affected family members. This
      family underscores the need to confirm array findings by FISH, both in the
      proband and family members, to discern implications for pathogenicity and more
      accurately define the recurrence risk. 

PMID- 25858704
TI  - Microduplications of 3p26.3p26.2 containing CRBN gene in patients with
      intellectual disability and behavior abnormalities.
AB  - We report on the clinical data and molecular cytogenetic findings in three
      unrelated patients presenting with intellectual disability and behavior
      abnormalities. An overlapping microduplication involving 3p26.2-26.3 was
      identified in these patients. All three aberrations were confirmed and proven to
      be parentally inherited. The sizes of the duplications were different, with a
      common minimal region of 423,754 bp containing two genes - TRNT1 and CRBN. Here,
      we hypothesize that the copy number gain of CRBN gene might be responsible for
      developmental delay/intellectual disability. 

PMID- 25858705
TI  - Minor Prenylated Flavonoids from the Twigs of Macarangaadenantha and Their
      Cytotoxic Activity.
AB  - Three new minor prenylated flavonoids, named macadenanthins A-C (1-3), together
      with three known ones (4-6), were isolated from the twigs of Macaranga adenantha.
      Their structures were elucidated on the basis of extensive spectroscopic analysis
      including NMR, UV and MS. The prenyl moieties in compounds 1-3 were further
      modified by cyclization and hydroxylation. The new compounds were tested for
      their cytotoxicity against four cancer cell lines (MCF-7, Hep G2, Hela and P388)
      and showed IC50 values in the range of 13.76-22.27 MUM.

PMID- 25858701
TI  - Development of protein mimics for intracellular delivery.
AB  - Designing delivery agents for therapeutics is an ongoing challenge. As treatments
      and desired cargoes become more complex, the need for improved delivery vehicles
      becomes critical. Excellent delivery vehicles must ensure the stability of the
      cargo, maintain the cargo's solubility, and promote efficient delivery and
      release. In order to address these issues, many research groups have looked to
      nature for design inspiration. Proteins, such as HIV-1 trans-activator of
      transcription (TAT) and Antennapedia homeodomain protein, are capable of crossing
      cellular membranes. However, due to the complexities of their structures, they
      are synthetically challenging to reproduce in the laboratory setting. Being able
      to incorporate the key features of these proteins that enable cell entry into
      simpler scaffolds opens up a wide range of opportunities for the development of
      new delivery reagents with improved performance. This review charts the
      development of protein mimics based on cell-penetrating peptides (CPPs) and how
      structure-activity relationships (SARs) with these molecules and their protein
      counterparts ultimately led to the use of polymeric scaffolds. These scaffolds
      deviate from the normal peptide backbone, allowing for simpler, synthetic
      procedures to make carriers and tune chemical compositions for application
      specific needs. Successful design of polymeric protein mimics would allow
      researchers to further understand the key features in proteins and peptides
      necessary for efficient delivery and to design the next generation of more
      efficient delivery reagents.

PMID- 25858706
TI  - Syndrome of inappropriate antidiuretic hormone in a bulldog with aspiration
      pneumonia.

PMID- 25858707
TI  - Iris metastasis from prostate carcinoma: a case report and review of the
      literature.
AB  - Despite the high incidence of prostate carcinoma, metastases of the uvea are very
      rare and the iris localization is even more. Only a few cases worldwide have been
      described so far. We report here the case of a 66-year-old man diagnosed with a
      metastatic prostate carcinoma. Nine months later, he developed brain and skin
      metastases. A couple of weeks later, the metastatic lesion appeared on his left
      iris. He has received whole brain radiation therapy including the iris lesion in
      the radiation fields. Through this case report and a literature review, we
      discuss the incidence, the different clinical presentations and the impact on the
      survival prognosis of this uncommon metastatic site. 

PMID- 25858708
TI  - [Individual patient data meta-analyses of randomized trials for the treatment of
      non-metastatic head and neck squamous cell carcinomas: Principles, results and
      perspectives].
AB  - Meta-analyses are considered as an important pillar of evidence-based medicine.
      The aim of this review is to describe the main principles of a meta-analysis and
      to use examples of head and neck oncology to demonstrate their clinical impact
      and methodological interest. The major role of individual patient data is
      outlined, as well as the superiority of individual patient data over meta
      analyses based on published summary data. The major clinical breakthrough of head
      and neck meta-analyses are summarized, regarding concomitant chemotherapy,
      altered fractionated chemotherapy, new regimens of induction chemotherapy or the
      use of radioprotectants. Recent methodological developments are described,
      including network meta-analyses, the validation of surrogate markers. Lastly, the
      future of meta-analyses is discussed in the context of personalized medicine. 

PMID- 25858709
TI  - Auto-inflammatory challenge of the endolymphatic sac--Cochlear damage measured by
      distortion product oto-acoustic emissions.
AB  - CONCLUSION: Twenty-five rats were challenged by an immunologic attack of the
      endolymphatic sac. After 6 months, distortion product oto-acoustic emissions
      (DPOAE) revealed a dysfunction of the outer hair cells and immunological active
      cells were observed in the endolymphatic sac. This information could contribute
      to the understanding of Meniere's disease. OBJECTIVES: This study investigated if
      an autoimmune challenge of the endolymphatic sac could affect DPOAE output
      measurements in rats. Also, a potential autoimmune cell infiltration of the
      endolymphatic sac was investigated. METHODS: Eighteen Lewis rats were immunized
      with a crude endolymphatic sac extract in complete Freund's adjuvant. Seven
      control animals were injected with Freund's adjuvant in saline. Cochlear damage
      was estimated by DPOAE dynamics 3 weeks and 6 months after the immunization.
      Infiltrative cells in the endolymphatic sac were investigated with transmission
      electron microscopy. RESULTS: The hearing assessment 6 months after immunization
      revealed a reduction of the DPOAE, on the full range of frequencies (2-63 kHz) in
      an average of the mean, of 2 dB +/- 1.1 in the immunized group compared to the
      controls (p < 0.05). The same test showed a 2.5 dB decrease from 2 to 5 kHz (p <
      0.01). Immunological active cells were observed in the endolymphatic sac in most
      of the immunized rats.

PMID- 25858710
TI  - Open for the future.

PMID- 25858711
TI  - Dento-legal: a modern-day Wolf Hall?

PMID- 25858712
TI  - Impact on the airway.

PMID- 25858713
TI  - Orthodontics: why 50?

PMID- 25858714
TI  - Fighting the stupidity.

PMID- 25858715
TI  - Dental education: galactic microscopes.

PMID- 25858716
TI  - The reaction...: GDC accountability hearing.

PMID- 25858718
TI  - Research reveals dentists are down in the mouth.

PMID- 25858720
TI  - Tour de dentistry.

PMID- 25858724
TI  - Polar molars.

PMID- 25858726
TI  - Photo story: new 200 m record set by 95-year-old dentist.

PMID- 25858728
TI  - Janet Clarke: 'We will increasingly see dentists being salaried'.

PMID- 25858729
TI  - Janine Brooks: 'I may no longer see patients, but I'm still in dentistry'.

PMID- 25858730
TI  - Professional standards and their escalating impact upon the dental profession.
AB  - This article highlights several areas of confusion that have arisen in relation
      to professional standards in the UK. In doing so, it provides a possible
      explanation for the fact that litigation levels against UK dentists, and also the
      level of regulatory challenge and criticism that they face, are both at levels
      far beyond those that are seen in virtually any other country in the world. 

PMID- 25858735
TI  - Current practice and factors influencing the provision of periodontal healthcare
      in primary dental care in Scotland: an explorative study.
AB  - AIMS: To understand current practice and the beliefs of dentists and hygienists
      towards factors which may influence the management of patients with periodontal
      diseases in primary dental care in Scotland. To inform the scope of a guidance
      publication and the future development of diagnostic analyses tools. METHODS: A
      qualitative approach of semi-structured telephone interviews with a randomly
      selected sample of dentists and hygienists was used. Interviews continued until
      saturation was reached and were audio-recorded and transcribed verbatim. The data
      were analysed using the method of framework analysis. To increase the
      participation of hygienists the topic guide was adapted into a self-reporting
      questionnaire and posted to all hygienists in Scotland. RESULTS: Eighteen
      dentists and three hygienists were interviewed. Key themes identified were extent
      of control over working environment, capabilities to treat appropriately and
      changing patients' oral hygiene behaviour. Factors which facilitated the
      management of patients with periodontal diseases were 'access to a hygienist' and
      'beliefs about capabilities', while 'routine and habit', 'motivation of patients'
      and 'time and money' were perceived as barriers. Some evidence of variation in
      treatment provision and of varying levels of confidence among practitioners about
      treating more advanced periodontal conditions was identified. Two hundred and
      thirty-seven hygienists returned the postal questionnaire. Agreement was found
      with the views of the interviewed hygienists on beliefs about capabilities and
      routine record-keeping. CONCLUSION: To improve the periodontal health of patients
      requires consideration of both extrinsic and intrinsic factors present in primary
      dental care. Practitioners would find having guidance on managing patients with
      basic periodontal examinations of three and four, referral criteria to secondary
      care, record-keeping and techniques to change patients' oral hygiene behaviour
      particularly useful. Applying the evaluative framework pre-publication indicated
      where knowledge translation interventions may be required in the future.

PMID- 25858736
TI  - A discourse of disconnection--challenges to clinical engagement and collaborative
      dental commissioning.
AB  - AIM: While doctors are moving centre-stage into managerial and leadership
      commissioning roles, the role of clinicians in NHS dental commissioning has
      retained a mainly representative model. In this paper we describe the discourse
      of 'rank and file' dental practitioners and the implications of this for clinical
      engagement and clinical leadership in dentistry. METHOD: As part of an NIHR study
      of NHS dental contracting a questionnaire was sent to 925 practitioners. The
      questionnaire included a free text box inviting further comment. We received 113
      lengthy narratives in 333 (43%) of the questionnaires returned and so undertook a
      discourse analysis of this data--focusing on the use of language, shared meaning
      and how practitioners portrayed their identity and activities. RESULTS: Three
      discursive repertoires were identified: professional subordination; a
      disconnected hierarchy; and a strained collegiality. Underpinning these
      repertoires was the sense of disjuncture between the macro-level (managerial) and
      micro-level (practice), and the problematic nature of clinical leadership in a
      profession where dentists' common identity is fractured by their individual
      clinical and business practice. CONCLUSIONS: This paper presents an insight into
      the views of dental practitioners in their own words, and the challenges of
      engaging dental practitioners in a new commissioning era.

PMID- 25858737
TI  - Use and knowledge of IOTN among GDPs in Scotland.
AB  - OBJECTIVES: To evaluate the use and knowledge of the index of orthodontic
      treatment need (IOTN) by general dental practitioners (GDPs) working within
      Scotland. SETTING: Scottish general dental services (SGDS). METHODS:
      Questionnaires were posted to randomly selected dentists (n=356) working within
      the SGDS for self-completion and return. MAIN OUTCOME MEASURES: Use of
      IOTN.Knowledge of IOTN Participants were asked to match 12 malocclusions to the
      correct IOTN category. Kappa statistics evaluated agreement to a gold standard.
      RESULTS: The overall response rate was 64%. Sixty-one percent of respondents did
      not use IOTN. The most common reason for using the index was to assess treatment
      eligibility (40.2%). The main reason for non-use was that it was only considered
      suitable for secondary dental care (27%). Over half (56%) of respondents had
      received IOTN training at undergraduate level. Knowledge of the index was found
      to be low--the mean level of agreement was k=0.42 (fair). 10.5% of respondents
      scored k>=0.61(substantial). The factors most likely to contribute to both use
      and knowledge of IOTN were having a postgraduate qualification and carrying out
      orthodontic treatment in practice. CONCLUSION: Overall use and knowledge of IOTN
      among GDPs in Scotland appears to still be low. More resources need to be
      directed towards improving both undergraduate and postgraduate orthodontic
      training with the focus on IOTN in particular.

PMID- 25858738
TI  - Person-centred care in dentistry--the patients' perspective.
AB  - OBJECTIVES: To develop an understanding of the key features of person-centred
      care (PCC) in relation to general dental practice from a patient's perspective.
      BACKGROUND: PCC is acknowledged as an important dimension of quality with
      'patient experience' increasingly used as a marker of quality within the NHS. A
      Dental Quality and Outcomes Framework (DQOF) is currently being piloted in the
      UK, which includes patient experience as one of the three domains. It is
      recognised that there is limited understanding of PCC within dentistry, with
      little evidence published on the subject. METHODS: This study uses qualitative
      methods to explore the views of 16 purposively sampled patients living in
      Southwest England. In-depth semi-structured interviews were recorded,
      transcribed, coded and analysed thematically. RESULTS: PCC was viewed as key in
      the delivery of high-quality care. Dimensions of PCC were identified and
      categorised as relational or functional aspects of care. Relational aspects of
      care were viewed as being central to the delivery of PCC with five components
      identified and named: connection, attitude, communication, empowerment and
      feeling valued. Functional aspects of care were identified as healthcare system
      and physical environment and were noted to influence PCC to a variable degree.
      CONCLUSION: A model of PCC in dentistry is proposed which has been generated from
      empirical evidence that represents the views of patients. It is hoped that this
      may inform and influence development of a tool to measure PCC within any future
      version of the DQOF.

PMID- 25858739
TI  - What are dental non-attenders' preferences for anxiety management techniques? A
      cross-sectional study based at a dental access centre.
AB  - OBJECTIVE: Dental anxiety is a barrier to attendance. Dental non-attenders may
      seek emergency care and may prefer to receive anxiety management measures for
      treatment required. Little is known about the preferences of these dental non
      attenders for different anxiety management techniques. Understanding such
      preferences may inform management pathways, improve experiences, alleviate
      anxieties and encourage a more regular attendance pattern. As such, the aim of
      this study was to gain a greater understanding of the dental anxiety of patients
      attending a dental access centre for emergency dental treatment and to ascertain
      preferences for different anxiety management techniques. DESIGN: Cross-sectional
      study involving self-completed questionnaires and clinical observation. SETTING:
      NHS Dental Access Centre, York, UK. SUBJECTS AND METHODS: Two hundred
      participants not registered with a general dental practitioner, aged 18 years or
      over, experiencing pain and self-referred were recruited on a consecutive
      sampling basis. Participants completed a questionnaire eliciting demographic and
      dental history details, dental anxiety and preferences for dental anxiety
      management options. MAIN OUTCOME MEASURES: Correlation of the modified dental
      anxiety scale with preference for different dental anxiety management techniques.
      RESULTS: No significant predictive factors were found that explained preferring
      local anaesthetic to sedation, or general anaesthesia for restorations or
      extractions. Those highly anxious were less likely to consider tell-show-do
      techniques (p=0.001) or watching explanatory videos (p=0.004) to be helpful for
      overcoming their anxieties than the low or moderate anxiety groups. CONCLUSIONS:
      People attending access centres may represent a group who are unwilling to
      explore non-pharmacological methods to overcome their anxieties. This supports
      the need for sedation to provide treatment. Future work may include exploring in
      more depth the thoughts and opinions of this group of patients to improve
      understanding of their complex dental attitudes. From this, more effective
      strategies may be developed to encourage regular dental attendance.

PMID- 25858740
TI  - Survival characteristics of 771 resin-retained bridges provided at a UK dental
      teaching hospital.
AB  - OBJECTIVE: To analyse the factors affecting the clinical performance and those
      influencing the survival of resin-retained bridgework provided at a UK dental
      teaching hospital between 1994 and 2001. DESIGN: A prospective analysis of
      restorations provided at a single centre using case notes with all patients
      invited for review to corroborate findings. SETTING: Department of Restorative
      Dentistry, University of Bristol Dental Hospital and School, Bristol, United
      Kingdom. SUBJECTS AND METHODS: Between January 1994 and December 2001, data
      regarding 1,000 consecutive resin-retained bridges provided at Bristol Dental
      Hospital and School were recorded. Data was available for 805 patients at the
      time of the study. Following invitation, 621 patients attended for a review
      appointment. Life table and Kaplan-Meir survival analysis were carried out for
      all restorations provided. RESULTS: The five-year and ten-year survival rates
      estimated by the life-table method are 80.8% (95% confidence interval 78.0-83.6%)
      and 80.4% (95% confidence interval 77.6-83.2%) respectively. The median survival
      cannot be estimated for this study as the survival probability remains above 80%
      even at the longest follow-up. Analysis of clinical variables influencing
      survival revealed that design of the restoration and experience of the operator
      providing the restoration were significant factors. Resin-retained bridges made
      with minimal tooth preparation are shown to be superior in terms of longevity
      than those for which other types of tooth preparation is made. Patient
      satisfaction with their treatment was high.

PMID- 25858757
TI  - Synthesis of Biofunctional Janus Particles.
AB  - Janus particles with anisotropic biofunctionalities are perfect models to mimic
      anisotropic architectures and directional interactions that occur in nature. It
      is therefore highly desirable to develop reliable and efficient methods to
      synthesize biofunctional Janus particles. Herein, a facile method combining
      seeded-emulsion polymerization and thiol-click chemistry has been developed to
      synthesize Janus particles with glucose moieties on one side. These biofunctional
      Janus particles show region-selective binding of protein, which represents a big
      step toward biomimicry, and demonstrates the potential of the bioJanus particles
      for targeted drug delivery and binding. 

PMID- 25858758
TI  - Particulate matter phagocytosis induces tissue factor in differentiating
      macrophages.
AB  - Airborne exposure to particulate matter with diameter < 10 mcM (PM10) has been
      linked to an increased risk of thromboembolic events, but the mechanisms are not
      completely understood. The aim of this study was to evaluate the effect of PM10
      phagocytosis on the release of procoagulant molecules in human differentiating
      macrophages, and that of PM10 inhalation in an experimental model in rats. Human
      monocytes were separated from the peripheral blood by the lymphoprep method,
      differentiated in vitro and treated with standard PM10 or vehicle. Sprague-Dawley
      rats were instilled intratracheally with PM10 or vehicle alone. The outcome was
      expression of proinflammatory genes and of tissue factor (TF). In human
      differentiating macrophages, PM10 exposure upregulated inflammatory genes, but
      most consistently induced TF mRNA and protein levels, but not TF protein
      inhibitor, resulting in increased TF membrane expression and a procoagulant
      phenotype. Differentiation towards the anti-inflammatory M2 phenotype inhibited
      PM10 -mediated TF expression. TF induction required phagocytosis of PM10 ,
      whereas phagocytosis of inert particles was less effective. PM10 phagocytosis was
      associated with a gene expression profile consistent with intracellular retention
      of iron, inducing oxidative stress. Both PM10 and iron activated the stress
      kinases ERK1/2 pathway, involved in the induction of TF expression. In rats,
      alveolar exposure to PM10 was associated with pulmonary recruitment of
      inflammatory cells and resulted in local, but not systemic, induction of TF
      expression, which was sufficient to increase circulating TF levels. In
      conclusion, TF induction by differentiating lung macrophages, activated following
      phagocytosis, contributes to the increased risk of thromboembolic complications
      associated with PM10 exposure.

PMID- 25858759
TI  - Effect of diet-induced obesity or type 1 or type 2 diabetes on corneal nerves and
      peripheral neuropathy in C57Bl/6J mice.
AB  - We determined the impact diet-induced obesity (DIO) and types 1 and 2 diabetes
      have on peripheral neuropathy with emphasis on corneal nerve structural changes
      in C57Bl/6J mice. Endpoints examined included nerve conduction velocity, response
      to thermal and mechanical stimuli and innervation of the skin and cornea. DIO
      mice and to a greater extent type 2 diabetic mice were insulin resistant. DIO and
      both types 1 and 2 diabetic mice developed motor and sensory nerve conduction
      deficits. In the cornea of DIO and type 2 diabetic mice there was a decrease in
      sub-epithelial corneal nerves, innervation of the corneal epithelium, and corneal
      sensitivity. Type 1 diabetic mice did not present with any significant changes in
      corneal nerve structure until after 20 weeks of hyperglycemia. DIO and type 2
      diabetic mice developed corneal structural damage more rapidly than type 1
      diabetic mice although hemoglobin A1 C values were significantly higher in type 1
      diabetic mice. This suggests that DIO with or without hyperglycemia contributes
      to development and progression of peripheral neuropathy and nerve structural
      damage in the cornea. 

PMID- 25858760
TI  - Adaptation and Validation of the Instrument Treatment Outcomes Profile to the
      Chilean Population.
AB  - This study aims to psychometrically validate the Chilean version of the treatment
      outcomes profile (TOP), an instrument that can be used by treatment centers to
      monitor the results of drug and alcohol treatments. Specifically, this study is
      interested in evaluating the inter-rater reliability, concurrent validity, change
      sensitivity and discriminant and construct validity of this instrument. The TOP
      was modified to reflect the Chilean context and then applied in three successive
      stages: an initial application at the beginning of treatment, a retest after
      1week, and a follow up after a month. The sample was composed of 411 users of
      different types of drugs who were in treatment centers in the three largest
      regions of the country. The TOP reliability was greater than .75 for most items.
      Regarding concurrent validity, all the coefficients were in the expected
      direction and statistically significant. Change over time, as measured by Cohen's
      d statistic and the Reliable Change Index, was significant for most items. Users
      in treatment for less than 3months showed higher alcohol consumption (odds ratio
      [OR]=1.07; 95% confidence interval [95% CI]: 1.01-1.13), poorer psychological
      health (OR=0.94; 95% CI: 0.87-1.00), fewer days worked (0.56; 0.95-0.99) and
      poorer housing conditions (OR=2.76; 95% CI: 1.22-6.23) than did their
      counterparts who had more than 3months of treatment. Researchers extracted six
      components with eigenvalues greater than one, accounting for 69.0% of the total
      variance. In general, the Chilean TOP is a reliable and valid mechanism to
      monitor outcomes of people treated for problems with drug and alcohol abuse in
      Chile, but further validation work is required in some dimensions. 

PMID- 25858761
TI  - Factors Associated with Recidivism among Corrections-Based Treatment Participants
      in Rural and Urban Areas.
AB  - The majority of corrections-based treatment outcome studies focus on individuals
      paroling to urban areas; thus there is a significant gap in the literature on
      outcomes, including recidivism, among individuals paroling to non-urban and rural
      communities. This study examines differences in factors associated with
      recidivism among former corrections-based treatment participants living in urban
      and rural communities following release. Analyses focused on secondary data
      collected from treatment participants in one southeastern state over a four year
      period between July 2006 and June 2010 including both baseline (treatment intake)
      and follow-up data (12-months post-release). Findings indicated that individuals
      in urban areas were 2.4 times more likely to recidivate than rural individuals.
      Other factors identified in separate rural and urban analyses also emerged as
      significant predictors in the overall model including age, gender, race,
      employment and drug use. Overall, these findings suggest that corrections-based
      treatment participants living in urban and rural areas following release may
      share similar risk factors for recidivism. However, rural areas may be protective
      for returning to custody despite the presence of some of these risks. 

PMID- 25858762
TI  - An additional clinical sign of 17q21.31 microdeletion syndrome: preaxial
      polydactyly of hands with broad thumbs.

PMID- 25858763
TI  - Protective effects of quercetin against chronic mixed reflux esophagitis in rats
      by inhibiting the nuclear factor-kappaB p65 and interleukin-8 signaling pathways.
AB  - OBJECTIVE: To observe the effects of quercetin on chronic mixed reflux
      esophagitis (RE) in rats by inhibiting the nuclear factor-kappaB p65 (NF
      kappaBp65) and interleukin-8 (IL-8) signaling pathways. METHODS: Forty-eight
      healthy male Sprague-Dawley rats were randomly divided into six groups, with 8
      rats in each group: the normal intact group, the sham operation group, the RE
      control group, the RE group treated with omeprazole or 100 mg/kg and 200 mg/kg
      quercetin. The animals were sacrificed after 6 weeks of different interventions.
      The pathological characteristics of esophageal mucosa were observed according to
      the diagnostic criteria and the expressions of NF-kappaBp65 and IL-8 were
      assessed by immunohistochemistry and real-time polymerase chain reaction.
      RESULTS: Compared with the RE control group, esophageal mucosal injury was
      improved and the expressions of NF-kappaBp65 and IL-8 were significantly
      decreased in the RE group treated with omeprazole or quercetin (P < 0.05).
      Compared with the omeprazole group, the gross and microscopic scores of
      esophageal mucosal injury and the expressions of NF-kappaBp65 and IL-8 in the 100
      mg/kg and 200 mg/kg quercetin groups were not increased (P > 0.05). There was no
      statistically significant difference between the RE groups treated with 100 mg/kg
      quercetin and 200 mg/kg quercetin. CONCLUSION: Quercetin can prevent esophageal
      mucosal injury in RE rats by suppressing the NF-kappaBp65 and IL- 8 signaling
      pathways.

PMID- 25858764
TI  - New anthropometry-based age- and sex-specific reference values for urinary 24
      hour creatinine excretion based on the adult Swiss population.
AB  - BACKGROUND: Urinary creatinine excretion is used as a marker of completeness of
      timed urine collections, which are a keystone of several metabolic evaluations in
      clinical investigations and epidemiological surveys. METHODS: We used data from
      two independent Swiss cross-sectional population-based studies with standardised
      24-hour urinary collection and measured anthropometric variables. Only data from
      adults of European descent, with estimated glomerular filtration rate (eGFR) >=60
      ml/min/1.73 m2 and reported completeness of the urinary collection were retained.
      A linear regression model was developed to predict centiles of the 24-hour
      urinary creatinine excretion in 1,137 participants from the Swiss Survey on Salt
      and validated in 994 participants from the Swiss Kidney Project on Genes in
      Hypertension. RESULTS: The mean urinary creatinine excretion was 193 +/- 41
      MUmol/kg/24 hours in men and 151 +/- 38 MUmol/kg/24 hours in women in the Swiss
      Survey on Salt. The values were inversely correlated with age and body mass index
      (BMI). CONCLUSIONS: We propose a validated prediction equation for 24-hour
      urinary creatinine excretion in the general European population, based on readily
      available variables such as age, sex and BMI, and a few derived normograms to
      ease its clinical application. This should help healthcare providers to interpret
      the completeness of a 24-hour urine collection in daily clinical practice and in
      epidemiological population studies.

PMID- 25858765
TI  - Development of a quantitative PCR assay for monitoring Streptococcus agalactiae
      colonization and tissue tropism in experimentally infected tilapia.
AB  - Streptococcus agalactiae has become one of the most important emerging pathogens
      in the aquaculture industry and has resulted in large economic losses for tilapia
      farms in China. In this study, three pairs of specific primers were designed and
      tested for their specificities and sensitivities in quantitative real-time
      polymerase chain reactions (qPCRs) after optimization of the annealing
      temperature. The primer pair IGS-s/IGS-a, which targets the 16S-23S rRNA
      intergenic spacer region, was finally chosen, having a detection limit of 8.6
      copies of S. agalactiae DNA in a 20 MUL reaction mixture. Bacterial tissue
      tropism was demonstrated by qPCR in Oreochromis niloticus 5 days post-injection
      with a virulent S. agalactiae strain. Bacterial loads were detected at the
      highest level in brain, followed by moderately high levels in kidney, heart,
      spleen, intestines, and eye. Significantly lower bacterial loads were observed in
      muscle, gill and liver. In addition, significantly lower bacterial loads were
      observed in the brain of convalescent O. niloticus 14 days post-injection with
      several different S. agalactiae strains. The qPCR for the detection of S.
      agalactiae developed in this study provides a quantitative tool for investigating
      bacterial tissue tropism in infected fish, as well as for monitoring bacterial
      colonization in convalescent fish.

PMID- 25858766
TI  - Facile chemoenzymatic synthesis of biotinylated heparosan hexasaccharide.
AB  - A biotinylated heparosan hexasaccharide was synthesized using a one-pot multi
      enzyme strategy, in situ activation and transfer of N-trifluoroacetylglucosamine
      (GlcNTFA) to a heparin backbone significantly improved the synthetic efficiency.
      The biotinylated hexasaccharide could serve as a flexible core to diversify its
      conversion into heparan sulfate isoforms with potential biological applications
      and therapeutics. 

PMID- 25858767
TI  - Acute toxicity of CCl4 but not of paracetamol induces a transcriptomic signature
      of fibrosis in precision-cut liver slices.
AB  - In rat in vivo, both paracetamol (APAP) and carbon tetrachloride (CCl4) induce
      liver necrosis, but long-term treatment with CCl4, in contrast to paracetamol,
      causes liver fibrosis. The aim of this study was to perform transcriptomic
      analysis to compare the early changes in mRNA expression profiles induced by APAP
      and CCl4 in the rat precision-cut liver slice model (PCLS) and to identify early
      markers that could predict fibrosis-inducing potential. Microarray data of rat
      PCLS exposed to APAP andCCl4was generated using a toxic dose based on decrease in
      ATP levels. Toxicity pathway analysis using a custom made fibrosis-related gene
      list showed fibrosis as one of the predominant toxic endpoints in CCl4-treated,
      but not in APAP-treated PCLS. Moreover, genes which have a role in fibrosis such
      as alpha-B crystallin, jun proto-oncogene, mitogen-activated protein kinase 6,
      serpin peptidase inhibitor and also the transcription factor Kruppel-like-factor
      6 were up-regulated by CCl4, but not by APAP. Predicted activation or inhibition
      of several upstream regulators due to CCl4 is in accordance with their role in
      fibrosis. In conclusion, transcriptomic analysis of PCLS successfully identified
      the fibrotic potential of CCl4 as opposed to APAP. The application of PCLS as an
      ex vivo model to identify early biomarkers to predict the fibrogenic potential of
      toxic compounds should be further explored. 

PMID- 25858768
TI  - [Recurrent diffuse alveolar hemorrhage in systemic lupus erytematosus treated
      with rituximab and immunoglobulins].

PMID- 25858769
TI  - Common variants of chemokine receptor gene CXCR3 and its ligands CXCL10 and
      CXCL11 associated with vascular permeability of dengue infection in peninsular
      Malaysia.
AB  - Dengue causes significantly more human disease than any other arboviruses. It
      causes a spectrum of illness, ranging from mild self-limited fever, to severe and
      fatal dengue hemorrhagic fever, as evidenced by vascular leakage and
      multifactorial hemostatic abnormalities. There is no specific treatment available
      till date. Evidence shows that chemokines CXCL10, CXCL11 and their receptor CXCR3
      are involved in severity of dengue, but their genetic association with the
      susceptibility of vascular leakage during dengue infection has not been reported.
      We genotyped 14 common variants of these candidate genes in 176 patients infected
      with dengue. rs4859584 and rs8878 (CXCL10) were significantly associated with
      vascular permeability of dengue infection (P<0.05); while variants of CXCL11
      showed moderate significance of association (P=0.0527). Haplotype blocks were
      constructed for genes CXCL10 and CXCL11 (5 and 7 common variants respectively).
      Haplotype association tests performed revealed that, "CCCCA" of gene CXCL10 and
      "AGTTTAC" of CXCL11 were found to be significantly associated with vascular
      leakage (P=0.0154 and 0.0366 respectively). In summary, our association study
      further strengthens the evidence of the involvement of CXCL10 and CXCL11 in the
      pathogenesis of dengue infection. 

PMID- 25858770
TI  - Postoperative radiation therapy for osseous metastasis: Outcomes and predictors
      of local failure.
AB  - PURPOSE: To evaluate patterns and predictors of local failure in patients
      undergoing postoperative radiation therapy (RT) for osseous metastases. METHODS
      AND MATERIALS: Patients undergoing postoperative RT for bone metastases between
      June 2008 and January 2012 were retrospectively reviewed. Patterns of local
      failure were assessed, and Fine and Gray's univariable and multivariable analyses
      (MVA) were used to evaluate factors associated with local progression, including
      dose intensity of RT (biological equivalent dose, BED, Gy10) and percent coverage
      of the surgical hardware by the RT fields. Additional predictors were similarly
      assessed, including patient (eg, age, performance status), disease (eg, tumor
      type, metastasis site), and treatment (eg, interval from surgery to RT)
      characteristics. RESULTS: A total of 82 cases were followed for a median of 4.3
      months (11.5 months among living patients) after treatment completion. Median BED
      was 39 Gy10 (range, 14-60), and RT fields covered an average of 71% (standard
      deviation, 26%) of the hardware. Fourteen cases (17%) experienced local
      progression. Although most (71%) failures occurred within the RT fields, 29%
      occurred marginally or out of field, but adjacent to surgical hardware.
      Increasing coverage of the surgical hardware by RT fields was associated with a
      reduced risk of local failure in MVA (hazard ratio [HR], 0.10; 95% confidence
      interval [CI], 0.012-0.82; P = .03), whereas a greater risk of failure was seen
      with increasing time between surgery and RT (HR, 1.03; 95% CI, 1.01-1.06; P =
      .01). Extremity rather than spinal site trended toward a greater risk of failure
      but did not reach significance (HR, 3.79; 95% CI, 0.96-14.89; P = .057). BED >=39
      Gy10 did not predict local failure (P = .51) in MVA. CONCLUSIONS: Current
      strategies achieve good outcomes after postoperative RT for osseous metastases.
      Greater coverage of the surgical hardware with RT fields and avoiding delays
      between surgery and postoperative RT should be considered to reduce recurrence
      risk for patients with bone metastases requiring surgical stabilization.

PMID- 25858771
TI  - Increased radiation dose heterogeneity within the prostate predisposes to
      urethral strictures in patients receiving moderately hypofractionated prostate
      radiation therapy.
AB  - PURPOSE: The purpose of this study was to determine whether radiation dose
      inhomogeneity within the prostate predisposes to late urinary strictures after
      moderately hypofractionated definitive external beam radiation therapy for
      prostate cancer. METHODS AND MATERIALS: One hundred seventy-three men with
      clinically localized prostate cancer met the inclusion criteria for this
      analysis. All patients received 70 Gy to the prostate delivered over 28
      fractions, had at least 2 years of clinical follow-up, and had dose-volume
      histogram information available for review. The endpoint of this study was the
      development of a urethral stricture that required a procedural intervention such
      as urethral dilation or suprapubic catheterization. Dosimetric parameters were
      evaluated for effect on the rate of urethral stricture formation by univariate
      Cox proportional hazards modeling. RESULTS: The median follow-up was 49.5 months
      (range, 24.6-108 months). At 5 years, the actuarial rate of intervention for
      urethral strictures across all patients was 4.9%. The maximum point dose within
      the prostate (P = .034, hazard ratio = 1.006) and the mean prostate dose (P =
      .039, hazard ratio = 1.004) were the only parameters predictive of urethral
      stricture formation. All patients who developed a urethral stricture were treated
      by a plan with a maximum prostate dose of >75 Gy (median, 77.67 Gy). CONCLUSIONS:
      For patients receiving moderately hypofractionated prostate radiation therapy
      over 28 fractions, a maximum point dose of 75 Gy within the prostate was
      associated with an increased probability of developing a urethral stricture that
      required procedural intervention. The hypothesis that hypofractionation increases
      susceptibility to toxicity from heterogeneity within the prostate should be
      confirmed by analyzing data from randomized trials with a conventionally
      fractionated control arm for comparison.

PMID- 25858772
TI  - Dosimetric impact of setup accuracy for an electron breast boost technique.
AB  - PURPOSE: To determine the setup error on an electron breast boost technique using
      daily cone beam computed tomography (CBCT). Patient and setup attributes were
      studied as contributing factors to the accuracy. METHODS AND MATERIALS:
      Reproducibility of a modified lateral decubitus position breast boost setup was
      verified for 33 patients using CBCT. Three-dimensional matching was performed
      between the CBCT and the initial planning CT for each boost fraction by matching
      the tumor bed and/or surgical clips. The dosimetric impact of the daily
      positioning error was achieved by rerunning the initial treatment plans
      incorporating the recorded shifts to study the dose differences. Breast
      compression, decubitus angle, tumor bed location and volume, and cup size were
      studied for their contribution to setup error. RESULTS: The range of setup errors
      was: 1.5 cm anterior to 9 mm posterior, 1.3 cm superior to 2.3 cm inferior, and
      3.2 cm medial to 2.4 cm lateral. Seven patients had setup errors that were >=2-cm
      margin placed on the tumor bed and scar. Four of those 7 patients had
      unacceptable coverage as defined by the volume of the tumor bed plus scar that is
      covered by the 90% isodose line (V90) compared with the original plan. All other
      patients had no discernible difference in the coverage (V90). The use of
      compression, tumor bed location, or volumes >20 mL showed no effect on coverage.
      CONCLUSIONS: In general, this study supported that a 2-cm margin was adequate (29
      of 33 patients) when patients are treated under typical conditions. Care should
      be taken when high electron energies are selected because the coverage at depth
      is more difficult to maintain in the clinical environment.

PMID- 25858774
TI  - Cardiovascular lifetime risk in patients with low risk in the short term.
      Association with carotid atheromatosis.

PMID- 25858773
TI  - Physiological consequences of abnormal connectivity in a developmental epilepsy.
AB  - OBJECTIVE: Many forms of epilepsy are associated with aberrant neuronal
      connections, but the relationship between such pathological connectivity and the
      underlying physiological predisposition to seizures is unclear. We sought to
      characterize the cortical excitability profile of a developmental form of
      epilepsy known to have structural and functional connectivity abnormalities.
      METHODS: We employed transcranial magnetic stimulation (TMS) with simultaneous
      electroencephalographic (EEG) recording in 8 patients with epilepsy from
      periventricular nodular heterotopia and matched healthy controls. We used
      connectivity imaging findings to guide TMS targeting and compared the evoked
      responses to single-pulse stimulation from different cortical regions. RESULTS:
      Heterotopia patients with active epilepsy demonstrated a relatively augmented
      late cortical response that was greater than that of matched controls. This
      abnormality was specific to cortical regions with connectivity to subcortical
      heterotopic gray matter. Topographic mapping of the late response differences
      showed distributed cortical networks that were not limited to the stimulation
      site, and source analysis in 1 subject revealed that the generator of abnormal
      TMS-evoked activity overlapped with the spike and seizure onset zone.
      INTERPRETATION: Our findings indicate that patients with epilepsy from gray
      matter heterotopia have altered cortical physiology consistent with
      hyperexcitability, and that this abnormality is specifically linked to the
      presence of aberrant connectivity. These results support the idea that TMS-EEG
      could be a useful biomarker in epilepsy in gray matter heterotopia, expand our
      understanding of circuit mechanisms of epileptogenesis, and have potential
      implications for therapeutic neuromodulation in similar epileptic conditions
      associated with deep lesions.

PMID- 25858775
TI  - Recent Progress towards Transition-Metal-Catalyzed Synthesis of Fluorenes.
AB  - Fluorenes are a commonly encountered structural motif in materials science,
      pharmaceutical chemistry, and organic synthesis. Among various strategies towards
      the synthesis of this unique structure, transition metal-catalyzed
      functionalization has emerged as one of the most efficient methods. This
      Minireview presents an overview of the recent advances in this emerging area by
      highlighting the reactions' specificity and applicability and, where possible,
      provides a mechanistic rationale. 

PMID- 25858776
TI  - SNARE protein analog-mediated membrane fusion.
AB  - Fusion of lipid membranes to form a single bilayer is an essential process for
      life and provides important biological functions including neurotransmitter
      release. Membrane fusion proteins facilitate approximation of interacting
      membranes to overcome the energy barrier. In case of synaptic transmission,
      proteins involved are known as soluble N-ethylmaleimide-sensitive-factor
      attachment receptor (SNARE) proteins. The SNAREs from synaptic vesicles interact
      with the SNAREs from the target membrane to form a coiled-coil bundle of four
      helices, thus pulling the membranes tightly together and initiating fusion.
      However, it remains unclear how these proteins function at molecular level.
      Natural systems are often too complex to obtain unambiguous results. Simple model
      systems mimicking natural proteins in synthetic lipid bilayers are powerful tools
      for obtaining insights into this essential biological process. An important
      advantage of such systems is their well-defined composition, which can be
      systematically varied in order to fully understand events at molecular level. In
      this review, selected model systems are presented based upon specific
      interactions between recognition units embedded in separate lipid bilayers
      mimicking native SNARE protein-mediated membrane fusion.

PMID- 25858777
TI  - Exploring women's beliefs and perceptions about healthy eating blogs: a
      qualitative study.
AB  - BACKGROUND: Chronic diseases are the leading cause of death (63%) worldwide. A
      key behavioral risk factor is unhealthy eating. New strategies must be identified
      and evaluated to improve dietary habits. Social media, such as blogs, represent a
      unique opportunity for improving knowledge translation in health care through
      interactive communication between health consumers and health professionals.
      Despite the proliferation of food and lifestyle blogs, no research has been
      devoted to understanding potential blog readers' perceptions of healthy eating
      blogs written by dietitians. OBJECTIVE: To identify women's salient beliefs and
      perceptions regarding the use of healthy eating blogs written by dietitians
      promoting the improvement of their dietary habits. METHODS: We conducted a
      qualitative study with female Internet users living in the Quebec City, QC, area
      with suboptimal dietary habits. First, the women explored 4 existing healthy
      eating blogs written in French by qualified dietitians. At a focus group 2-4
      weeks later, they were asked to discuss their experience and perceptions. Focus
      group participants were grouped by age (18-34, 35-54, and 55-75 years) and by
      their use of social media (users/nonusers). Using a questionnaire based on the
      Theory of Planned Behavior, participants were asked to identify salient beliefs
      underlying their attitudes (advantages/disadvantages), subjective norms (what
      people important to them would think), and perceptions of control
      (facilitators/barriers) regarding the use of a healthy eating blog written by a
      dietitian to improve dietary habits. Discussion groups were audiotaped,
      transcribed verbatim, coded, and a deductive content analysis was performed
      independently by 2 individuals using the NVivo software (version 10). RESULTS:
      All participants (N=33) were Caucasian women aged between 22 to 73 year. Main
      advantages perceived of using healthy eating blogs written by a dietitian were
      that they provided useful recipe ideas, improved lifestyle, were a credible
      source of information, and allowed interaction with a dietitian. Disadvantages
      included increased time spent on the Internet and guilt if recommendations were
      not followed. Important people who would approve were family, colleagues, and
      friends. Important people who could disapprove were family and doctors. Main
      facilitators were visually attractive blogs, receiving an email notification
      about new posts, and finding new information on the blog. Main barriers were too
      much text, advertising on the blog, and lack of time. CONCLUSIONS: The women in
      this study valued the credibility of healthy eating blogs written by dietitians
      and the contact with dietitians they provided. Identifying salient beliefs
      underlying women's perceptions of using such blogs provides an empirically
      supported basis for the design of knowledge translation interventions to help
      prevent chronic diseases.

PMID- 25858778
TI  - Regional heterogeneity of expression of renal NPRs, TonEBP, and AQP-2 mRNAs in
      rats with acute kidney injury.
AB  - To understand the pathophysiology of ischemia/reperfusion (I/R) - induced acute
      kidney injury (AKI), the present study defined changes in renal function, plasma
      renotropic hormones and its receptors in the kidney 2, 5, or 7 days after 45 min
      renal ischemia in rats. Blood urea nitrogen, plasma creatinine, and osmolarity
      increased 2 days after I/R injury and tended to return to control level 7 days
      after I/R injury. Decreased renal function tended to return to control level 5
      days after I/R injury. However, plasma concentrations of atrial natriuretic
      peptide and renin did not change. In control kidney, natriuretic peptide receptor
      (NPR)-A, -B and -C mRNAs were highly expressed in medulla (ME), inner cortex
      (IC), and outer cortex (OC), respectively, and tonicity-responsive enhancer
      binding protein (TonEBP), auqaporin-2 (AQP-2) and eNOS mRNAs were highly
      expressed in ME. NPR-A and -B mRNA expressions were markedly decreased 2 days
      after I/R injury. On 5 days after I/R injury, NPR-A mRNA expression increased in
      OC and recovered to control level in IC but not in ME. NPR-B mRNA expression was
      increased in OC, and recovered to control level in IC and ME. NPR-C mRNA
      expression was markedly decreased in OC 2 and 5 days after I/R injury. TonEBP,
      APQ-2 and eNOS mRNA expressions were markedly decreased 2 days after I/R injury
      and did not recover in ME 7 days after I/R injury. Therefore, we suggest that
      there is a regional heterogeneity of regulation of renal NPRs, TonEBP, and APQ-2
      mRNA in AKI.

PMID- 25858779
TI  - MUC5B expression and location in surfactant protein C mutations in children.
AB  - BACKGROUND: Mutations in Surfactant Protein C (SFTPC) can lead to fibrotic
      interstitial lung disease (ILD) with variable phenotypes, especially in children.
      The sources of phenotype variability are incompletely understood. A common MUC5B
      promoter variant rs35705950 is associated with adult Idiopathic Pulmonary
      Fibrosis (IPF). We examined whether MUC5B is similarly linked to ILD secondary to
      SFTPC mutations. METHODS: MUC5B concentration in bronchoalveolar lavage fluid
      (BALF) was measured in six pediatric patients with SFTPC mutations and diseased
      controls. Immunohistochemical localization of MUC5B was studied in fixed lung
      tissues in patients with SFTPC mutations, ABCA3 mutations, and controls.
      Genotyping for the MUC5B promoter variant rs35705950 was attempted in all
      samples. RESULTS: MUC5B glycoprotein was increased in BALF of patients with SFTPC
      mutations compared to diseased controls (P = 0.04). MUC5B was unexpectedly
      present in cells morphologically consistent with alveolar epithelial type II
      cells in patients with SFTPC mutations in the BRICHOS domain. Genotyping for the
      MUC5B promoter variant was successful in 18/27 patients, and there was no
      significant relationship between the MUC5B promoter variant and the BALF or MUC5B
      localization. CONCLUSION: MUC5B may play a role in the development of fibrosis in
      patients with SFTPC mutations, especially in patients with BRICHOS mutations.
      Understanding the role of MUC5B in adult and pediatric lung diseases may lead to
      a better understanding of the etiology of fibrotic lung disease as well as
      development of novel therapies.

PMID- 25858780
TI  - Plant macrofossil evidence for an early onset of the Holocene summer thermal
      maximum in northernmost Europe.
AB  - Holocene summer temperature reconstructions from northern Europe based on
      sedimentary pollen records suggest an onset of peak summer warmth around 9,000
      years ago. However, pollen-based temperature reconstructions are largely driven
      by changes in the proportions of tree taxa, and thus the early-Holocene warming
      signal may be delayed due to the geographical disequilibrium between climate and
      tree populations. Here we show that quantitative summer-temperature estimates in
      northern Europe based on macrofossils of aquatic plants are in many cases ca. 2 
      degrees C warmer in the early Holocene (11,700-7,500 years ago) than
      reconstructions based on pollen data. When the lag in potential tree
      establishment becomes imperceptible in the mid-Holocene (7,500 years ago), the
      reconstructed temperatures converge at all study sites. We demonstrate that
      aquatic plant macrofossil records can provide additional and informative insights
      into early-Holocene temperature evolution in northernmost Europe and suggest
      further validation of early post-glacial climate development based on multi-proxy
      data syntheses. 

PMID- 25858781
TI  - Soft Tissue Integration of Hydroxyapatite-Coated Abutments for Bone Conduction
      Implants.
AB  - PURPOSE: The protocol for bone conduction hearing implant surgery involves
      reduction of soft tissues around the abutment to minimize the risk of skin
      related complications. The present investigation was undertaken to demonstrate
      that hydroxyapatite-coated abutments provide improved soft tissue integration
      compared with conventional (pure titanium) abutments and are suitable for use
      without surgical removal of subepidermal soft tissues. MATERIALS AND METHODS:
      Forty-eight implants for bone conduction with two different types of abutments
      (test and control) were inserted in the skull parietal part of eight sheep. Test
      abutments had a hydroxyapatite-coated surface and a concave shape. Conventional
      titanium abutments were used as controls. A follow-up time of 4 weeks was used.
      Histomorphometric analyses of test and control samples were analyzed, and
      morphometric results were compared using mixed model analysis. RESULTS:
      Histological assessment showed healthy soft tissues around the abutments with
      limited or no signs of inflammation. Hydroxyapatite-coated abutments showed
      intimate dermal adherence, while less close contact was noted for control
      abutments. Statistically significant differences in mean pocket depth (0.4 vs 1.6
      mm, p = .0013) and epidermal downgrowth (0.6 vs 2.0 mm, p = .0003) between test
      and control abutments were recorded. CONCLUSION: The study confirms that
      hydroxyapatite-coated abutments resulted in a significant reduction in pocket
      depth and improved soft tissue integration compared with conventional titanium
      abutments, possibly by providing tight adherence at the interface. Statistically
      significant reduced pocket depth formation and epidermal downgrowth were
      recorded.

PMID- 25858782
TI  - Damage tolerance of indirect restorative materials (including PICN) after
      simulated bur adjustments.
AB  - OBJECTIVE: To analyze the damage tolerance of indirect restorative materials
      after grinding with diamond burs to simulate adjustments by clinicians and
      technicians. METHODS: Seven commercially available restorative materials (Mark
      II, ENAMIC, In-Ceram Alumina, VM 9, In-Ceram YZ, IPS e.max CAD) and an
      experimental one (PICN) were analyzed. Forty bending bars per material were
      fabricated according to manufacturer's instructions and lapped with 15 MUm
      diamond suspension. The initial flexural strength was determined in three-point
      bending on 10 specimens. Additionally the elastic modulus and Poisson's ratio
      were determined by the resonant frequency method. The remaining bending bars were
      divided into six groups (n=5) and subjected to standardized grinding with three
      different diamond grit burs (coarse, 151 MUm; medium, 107 MUm and extra fine 25
      MUm) and two grinding directions (transversal and longitudinal). The ground
      specimens were subsequently loaded to fracture and analyzed by SEM. RESULTS:
      Except for the YTZP bending bars, the initial materials strength of all tested
      materials decreased significantly with all diamond burs upon adjustments in both
      transversal and longitudinal grinding directions. The resistance of the ground
      materials to strength reduction follow the order from highest to least damage
      tolerant material: PICN>ENAMIC>Mark II>VM 9>In-Ceram Alumina>IPS e.max CAD. The
      loss in strength of all examined materials after longitudinal grinding is
      generally less compared to transversal grinding. The lowest loss in strength
      occurred for VM 9 (7.79%) and ENAMIC (9.18%) upon longitudinal grinding direction
      with extra fine and medium diamond grit bur, respectively. SIGNIFICANCE: The
      damage tolerance of restorative materials upon adjustments depends on specific
      mechanical properties and the adjustment procedure. The outcomes of the simulated
      grinding protocols of this study can be adopted clinically in terms of the
      selection of appropriate materials, burs and adjustment parameters.

PMID- 25858783
TI  - A critical evaluation of bond strength tests for the assessment of bonding to Y
      TZP.
AB  - OBJECTIVES: To compare three different designs for measuring the bond strength
      between Y-TZP ceramic and a composite material, before and after ceramic surface
      treatment, evaluating the influence of the size of the adhesive interface for
      each design. METHODS: 'Macro' tensile, microtensile, 'macro' shear, microshear,
      'macro' push-out, and micropush-out tests were carried out. Two Y-TZP surface
      treatments were evaluated: silanization (sil) and tribochemical silica coating
      (30MUm silica-modified Al2O3 particles+silanization) (TBS). Failure mode analysis
      of tested samples was also performed. RESULTS: Both the surface treatment and the
      size of the bonded interface significantly affected the results (p=0.00).
      Regardless of the type of surface treatment, the microtensile and microshear
      tests had higher values than their equivalent "macro" tests. However, the push
      out test showed the highest values for the "macro" test. The tensile tests showed
      the greatest variability in results. The tribochemical silica coating method
      significantly increased bond strength for all tests. SIGNIFICANCE: Different test
      designs can change the outcome for Y-TZP/cement interfaces, in terms of mean
      values and reliability (variability). The 'micro' tests expressed higher bond
      strengths than their equivalent 'macro' tests, with the exception of the push-out
      test (macro>micro).

PMID- 25858784
TI  - Antimicrobial activity of pomegranate fruit constituents against drug-resistant
      Mycobacterium tuberculosis and beta-lactamase producing Klebsiella pneumoniae.
AB  - CONTEXT: The global surge in multi-drug resistant bacteria and the imminence of
      tuberculosis pandemic necessitate alternative therapeutic approaches to augment
      the existing medications. Pomegranate, the fruit of Punica granatum Linn.
      (Punicaceae), widely recognized for potency against a broad spectrum of bacterial
      pathogens, deserves further investigation in this respect. OBJECTIVE: This study
      determines the therapeutic potential of pomegranate juice, extracts of non-edible
      peel prepared with methanol/water, and its four polyphenolic constituents, namely
      caffeic acid, ellagic acid, epigallocatechin-3-gallate (EGCG) and quercetin,
      against drug-resistant clinical isolates. MATERIALS AND METHODS: Phenotypic
      characterisation of Mycobacterium tuberculosis, extended-spectrum beta-lactamase
      (ESBL) and KPC-type carbapenemase producing Klebsiella pneumoniae was performed
      by biochemical and molecular methods. Resistance profiles of M. tuberculosis and
      K. pneumoniae were determined using LJ proportion and Kirby-Bauer methods,
      respectively. Pomegranate fruit extracts, and the compounds, were evaluated at a
      dose range of 1024-0.5 ug/mL, and 512-0.25 ug/mL, respectively, to determine
      minimum inhibitory (MIC) and bactericidal concentrations (MBC) against the drug
      resistant isolates by the broth micro-dilution method. RESULTS: The peel extracts
      exhibited greater antimycobacterial activity (MIC 64-1024 MUg/mL) than the
      potable juice (MIC 256 - > 1024 MUg/mL). EGCG and quercetin exhibited higher
      antitubercular (MIC 32-256 MUg/mL) and antibacterial (MIC 64-56 MUg/mL) potencies
      than caffeic acid and ellagic acid (MIC 64-512 MUg/mL). DISCUSSION AND
      CONCLUSION: The pomegranate fruit peel and pure constituents were active against
      a broad panel of M. tuberculosis and beta-lactamase producing K. pneumoniae
      isolates. EGCG and quercetin need further investigation for prospective
      application against respiratory infections.

PMID- 25858785
TI  - Drinking problems and mortality risk in the United States.
AB  - OBJECTIVE: We examine the links between 41 problems related to alcohol
      consumption and the risk of death among adults in the United States. METHOD: We
      use Cox proportional hazards models and data from the nationally representative
      prospective National Health Interview Survey-Linked Mortality Files (NHIS-LMF).
      RESULTS: Drinking problems are relatively common among moderate and heavy
      drinkers and these problems are associated with increases in the risk of death.
      The strongest associations between problem drinking and mortality involved cases
      in which physicians, family members, or friends intervened to suggest reduced
      drinking. Losing one's job because of drinking problems within their lifetime (HR
      = 1.36, 95% confidence interval [CI]: 1.11, 1.65) was strongly linked to
      mortality risk. Social risks were equally or more strongly linked to mortality
      than physiological consequences of alcohol abuse such as lifetime reports of
      needing a drink to stop shaking or getting sick (HR = 1.23, 95% CI: 1.09, 1.40).
      Most importantly, these associations were evident despite statistical controls
      for alcohol consumption levels and demographic, social, economic, behavioral,
      health, and geographic factors. CONCLUSIONS: Our results highlight the
      independent and additive effects of alcohol-related problems and alcohol
      consumption levels on the risk of death. We recommend that studies examining the
      mortality risks of alcohol consumption take into account drinking status and also
      specific drinking-related problems, paying particular attention to social
      problems related to alcohol use or abuse.

PMID- 25858786
TI  - Neighborhood-level and individual-level correlates of cannabis use among young
      persons living with HIV/AIDS.
AB  - INTRODUCTION: In addition to individual characteristics, there may be a wide
      range of environmental or neighborhood stressors that contribute to elevated
      cannabis use in groups of youth living with HIV/AIDS (YLHIV); however, the
      effects of social disorganization on cannabis use in YLHIV to date have not been
      studied. METHODS: We examined the effects of individual-level and neighborhood
      level factors by developing hierarchical generalized linear models estimating
      odds of current cannabis use (any use during the past 3 months) and daily
      cannabis use among a sample of YLHIV (N = 1921) currently receiving medical care.
      RESULTS: The final model for daily cannabis use in the past 3 months included
      significant positive effects associated with hostility (O.R. = 1.08, 95% C.I.:
      1.05, 1.11), being older (O.R. = 1.12, 95% C.I.: 1.05, 1.20), being a bisexual
      male (O.R. = 1.72, 95% C.I.: 1.10, 2.70), and residing in a community with a
      murder rate in the highest quartile (O.R. = 1.91, 95% C.I.: 1.27, 2.87), second
      highest quartile (O.R. = 1.62, 95% C.I.: 1.06, 2.46), or third highest quartile
      (O.R. = 1.52, 95% C.I.: 1.01, 2.30). DISCUSSION: This paper advances our
      knowledge of the multilevel factors associated with elevated cannabis use among
      groups of YLHIV and furthers our understanding of social and structural
      determinants of health in this population. Future research into cannabis use
      among YLHIV should consider, not only cannabis use within the context of the
      adjustment of living with HIV/AIDS, but also the stressors that characterize the
      environments in which groups of YLHIV live.

PMID- 25858787
TI  - The roles of outlet density and norms in alcohol use disorder.
AB  - BACKGROUND: Alcohol outlet density and norms shape alcohol consumption. However,
      due to analytic challenges we do not know: (a) if alcohol outlet density and
      norms also shape alcohol use disorder, and (b) whether they act in combination to
      shape disorder. METHODS: We applied a new targeted minimum loss-based estimator
      for rare outcomes (rTMLE) to a general population sample from New York City (N =
      4000) to examine the separate and combined relations of neighborhood alcohol
      outlet density and norms around drunkenness with alcohol use disorder. Alcohol
      use disorder was assessed using the World Mental Health Comprehensive
      International Diagnostic Interview (WMH-CIDI) alcohol module. Confounders
      included demographic and socioeconomic characteristics, as well as history of
      drinking prior to residence in the current neighborhood. RESULTS: Alcohol use
      disorder prevalence was 1.78%. We found a marginal risk difference for alcohol
      outlet density of 0.88% (95% CI 0.00-1.77%), and for norms of 2.05% (95% CI 0.89
      3.21%), adjusted for confounders. While each exposure had a substantial relation
      with alcohol use disorder, there was no evidence of additive interaction between
      the exposures. CONCLUSIONS: Results indicate that the neighborhood environment
      shapes alcohol use disorder. Despite the lack of additive interaction, each
      exposure had a substantial relation with alcohol use disorder and our findings
      suggest that alteration of outlet density and norms together would likely be more
      effective than either one alone. Important next steps include development and
      testing of multi-component intervention approaches aiming to modify alcohol
      outlet density and norms toward reducing alcohol use disorder.

PMID- 25858789
TI  - Sequential double second-order nonlinear optical switch by an acido-triggered
      photochromic cyclometallated platinum(II) complex.
AB  - An unprecedented DTE-based Pt(II) complex, 2(o), which stands as the first
      example of a sequential double nonlinear optical switch, induced first by
      protonation and next upon irradiation with UV light is presented.

PMID- 25858788
TI  - Ltb4r1 inhibitor: A pivotal insulin sensitizer?
AB  - The potent chemokine leukotriene B4 (LTB4) is increased in obesity, and is
      associated with insulin resistance. A recent article shows that inhibition of its
      receptor LTB4 receptor 1 (Ltb4r1) improves insulin sensitivity in muscle and
      liver via cytokine-independent mechanisms, and reduces proinflammatory immune
      cell infiltration in the adipose tissue. 

PMID- 25858790
TI  - The chlorinating behaviour of WCl6 towards alpha-aminoacids.
AB  - Cl/O interchange took place when WCl6 was allowed to interact with a series of
      alpha-aminoacids. The alpha-ammonium-acylchloride salts
      [NH2(CH2)3CHC(O)Cl][WOCl5], 1a, and [MeNH2CH2C(O)Cl][WOCl5], 1b, were afforded in
      ca. 55% yields from the reactions of WCl6 with, respectively, L-proline and
      sarcosine in CH2Cl2. By using other reaction media (hexane or CHCl3), the alpha
      amino-acylchloride complexes WOCl4[O=C(Cl)CH(CH2)3NH2], 5a, and
      WOCl4[O=C(Cl)CH(R)NHR'] (R = H, R' = Me, 5b; R = R' = H, 5c; R = Me, R' = H, 5d)
      were isolated in moderate to good yields from WCl6 and, respectively, L-proline,
      sarcosine, glycine and L-alanine. The formation of 5a,b is basically the result
      of HCl release from the parent compounds 1a,b. 5a represents a key intermediate
      in the course of the reaction leading to (WOCl4)2[MU:kappa(2)(O)-dkp], 2, dkp =
      (S,S)-octahydrodipyrrolo[1,2-a:1',2'-d]pyrazine-5,10-dione. 2 was optimally
      prepared from WCl6/L-proline under high temperature conditions. Hydrolytic
      treatment of 2 afforded the L-proline-derived 2,5-diketopiperazine (dkp), which
      was finally isolated with an overall yield of 70%. 1a,b were characterized by X
      ray diffractometry, thus providing very rare examples of crystallographically
      characterized acylchloride derivatives of alpha-aminoacids. DFT calculations were
      extensively carried out in order to shed light on structural and mechanistic
      features.

PMID- 25858791
TI  - Cranial suture-like gap and bone regeneration after transplantation of
      cryopreserved MSCs by use of a programmed freezer with magnetic field in rats.
AB  - Mesenchymal stem cells (MSCs) can be used for regeneration of various organs and
      tissues. A previous study revealed that cryopreserved MSCs, which were frozen by
      a programmed freezer with a magnetic field (Cells Alive System: CAS) and
      cryopreserved for 7 days in a -150 degrees C deep freezer, can maintain high
      survival and proliferation rates while retaining both adipogenic and osteogenic
      differentiation abilities. The purpose of this study was to examine MSC viability
      and tissue regenerative ability after long-term cryopreservation using a CAS
      freezer. MSCs were isolated from rat femora bone marrow and cryopreserved in a 
      150 degrees C deep freezer (CAS group) or directly cryopreserved in a deep
      freezer (Direct group). After 3 years, the cells were thawed and the number of
      viable cells was counted. Cell proliferation was also examined after 14 days in
      culture. For histological examination, forty 4-week-old Fischer 344 male rats
      received bone and sagittal suture defects with a diameter of 6.0mm, and MSCs (CAS
      or Direct group) cryopreserved for 1 year were grafted with membranes. Non
      cryopreserved MSCs (Control group) were transplanted to an additional twenty
      rats. The rats were sacrificed at 4, 8, 16, and 24 weeks after surgery. The
      parietal bones, including the sagittal suture, were observed under a light
      microscope and the extent of bone regeneration was measured. Our results indicate
      that MSCs survival and proliferation rates were significantly higher in the CAS
      group than in the Direct group. In the Control and CAS groups, a large amount of
      new bone formation and a suture-like gap was identified 24 weeks after
      transplantation, whereas only a small amount of new bone formation was observed
      in the Direct group. These results suggest that the CAS freezer is amenable to
      long-term cryopreservation of MSCs, which can be applied to the regeneration of
      various tissues, including bone tissue with suture-like gap formation.

PMID- 25858792
TI  - High aspect ratio 10-nm-scale nanoaperture arrays with template-guided metal
      dewetting.
AB  - We introduce an approach to fabricate ordered arrays of 10-nm-scale silica-filled
      apertures in a metal film without etching or liftoff. Using low temperature (<400
      degrees C) thermal dewetting of metal films guided by nano-patterned templates,
      apertures with aspect ratios up to 5:1 are demonstrated. Apertures form
      spontaneously during the thermal process without need for further processing.
      Although the phenomenon of dewetting has been well studied, this is the first
      demonstration of its use in the fabrication of nanoapertures in a spatially
      controllable manner. In particular, the achievement of 10-nm length-scale
      patterning at high aspect ratio with thermal dewetting is unprecedented. By
      varying the nanotemplate design, we show its strong influence over the positions
      and sizes of the nanoapertures. In addition, we construct a three-dimensional
      phase field model of metal dewetting on nano-patterned substrates. The simulation
      data obtained closely corroborates our experimental results and reveals new
      insights to template dewetting at the nanoscale. Taken together, this fabrication
      method and simulation model form a complete toolbox for 10-nm-scale patterning
      using template-guided dewetting that could be extended to a wide range of
      material systems and geometries. 

PMID- 25858793
TI  - Reading RVUs: How can we meet the informational needs of cardiologists?

PMID- 25858794
TI  - Upgrade ambulatory extra-aortic counterpulsation to full-support LVAD.

PMID- 25858795
TI  - Reply: Upgrade ambulatory extra-aortic counterpulsation to full-support LVAD.

PMID- 25858796
TI  - Experimental Myocardial Infarction Upregulates Circulating Fibroblast Growth
      Factor-23.
AB  - Myocardial infarction (MI) is a major cause of death worldwide. Epidemiological
      studies have linked vitamin D deficiency to MI incidence. Because fibroblast
      growth factor-23 (FGF23) is a master regulator of vitamin D hormone production
      and has been shown to be associated with cardiac hypertrophy per se, we explored
      the hypothesis that FGF23 may be a previously unrecognized pathophysiological
      factor causally linked to progression of cardiac dysfunction post-MI. Here, we
      show that circulating intact Fgf23 was profoundly elevated, whereas serum vitamin
      D hormone levels were suppressed, after induction of experimental MI in rat and
      mouse models, independent of changes in serum soluble Klotho or serum parathyroid
      hormone. Both skeletal and cardiac expression of Fgf23 was increased after MI.
      Although the molecular link between the cardiac lesion and circulating Fgf23
      concentrations remains to be identified, our study has uncovered a novel heart
      bone-kidney axis that may have important clinical implications and may inaugurate
      the new field of cardio-osteology.

PMID- 25858797
TI  - Biomimetic total synthesis of santalin Y.
AB  - A biomimetic total synthesis of santalin Y, a structurally complex but racemic
      natural product, is described. The key step is proposed to be a (3+2)
      cycloaddition of a benzylstyrene to a "vinylogous oxidopyrylium", which is
      followed by an intramolecular Friedel-Crafts reaction. This cascade generates the
      unique oxafenestrane framework of the target molecule and sets its five
      stereocenters in one operation. Our work provides rapid access to santalin Y and
      clarifies its biosynthetic relationship with other colorants isolated from red
      sandalwood. 

PMID- 25858798
TI  - Fatty acid composition of the postmortem prefrontal cortex of patients with
      schizophrenia, bipolar disorder, and major depressive disorder.
AB  - Postmortem brain studies have shown abnormal levels of n-3 polyunsaturated fatty
      acids (PUFAs), especially docosahexaenoic acid, in the frontal cortex
      (particularly the orbitofrontal cortex) of patients with depression,
      schizophrenia, or bipolar disorder. However, the results from regions in the
      frontal cortex other than the orbitofrontal cortex are inconsistent. In this
      study we investigated whether patients with schizophrenia, bipolar disorder, or
      major depressive disorder have abnormalities in PUFA levels in the prefrontal
      cortex [Brodmann area (BA) 8]. In postmortem studies, fatty acids in the
      phospholipids of the prefrontal cortex (BA8) were evaluated by thin layer
      chromatography and gas chromatography. Specimens were evaluated for patients with
      schizophrenia (n=15), bipolar disorder (n=15), or major depressive disorder
      (n=15) and compared with unaffected controls (n=15). In contrast to previous
      studies, we found no significant differences in the levels of PUFAs or other
      fatty acids in the prefrontal cortex (BA8) between patients and controls.
      Subanalysis by sex also showed no significant differences. No significant
      differences were found in any individual fatty acids between suicide and non
      suicide cases. These psychiatric disorders might be characterized by very
      specific fatty acid compositions in certain areas of the brain, and BA8 might not
      be involved in abnormalities of PUFA metabolism. 

PMID- 25858799
TI  - Non-suicidal self-injury as a predictor of active and passive suicidal ideation
      among Iraq/Afghanistan war veterans.
AB  - The present study examined the association between lifetime non-suicidal self
      injury (NSSI) and current suicidal ideation among Iraq/Afghanistan veterans. NSSI
      was positively associated with passive, active, and concurrent active-passive
      suicidal ideation at the bivariate level. NSSI remained a predictor of active,
      OR=5.15, and concurrent active-passive suicidal ideation, OR=7.01, when other
      risk factors were considered. These findings suggest that NSSI may be a
      particularly useful marker of active suicidal ideation among veterans. 

PMID- 25858800
TI  - Genetic association analyses of neuregulin 1 gene polymorphism with endopheontype
      for sociality of Korean autism spectrum disorders family.
AB  - To determine the genetic association between qualitative and quantitative traits
      of autism spectrum disorder (ASD) and neuregulin 1 (NRG1)-a schizophrenia
      candidate gene-we examined six single nucleotide polymorphisms (SNPs) in NRG1
      using a family-based association test (FBAT) in Korean families with ASD.
      rs35753505 and rs6994992 SNPs in NRG1 revealed a statistically significant family
      based association with three quantitative traits for sociality. 

PMID- 25858801
TI  - Thyroid hormones and adult interpersonal violence among women with borderline
      personality disorder.
AB  - Elevated T3 levels have been reported in men with antisocial behavior. The aim of
      the present study was to investigate the relationship between thyroid hormones
      and expressed adult interpersonal violence in female patients with borderline
      personality disorder (BPD). Furthermore, expressed adult interpersonal violence
      in female BPD patients was compared to healthy female controls. A total of 92
      clinically euthyroid women with BPD and 57 healthy women were assessed with the
      Karolinska Interpersonal Violence Scales (KIVS). Baseline thyroid function was
      evaluated by measuring plasma free and bound triiodothyronine (FT3 and T3),
      thyroxine (FT4 and T4), and thyroid-stimulating hormone (TSH) with immunoassays
      in patients. Plasma cortisol was also measured. Among females with BPD, expressed
      interpersonal violence as an adult showed a significant positive correlation with
      the T3 levels. The mean expression of interpersonal violence as an adult was
      significantly higher in BPD patients as compared to healthy controls. The
      multiple regression model indicated that two independent predictors of KIVS
      expressed interpersonal violence as an adult: T3 and comorbid diagnosis of
      alcohol abuse. Association between T3 levels and violent/aggressive behavior
      earlier reported exclusively in male samples may be valid also in females with
      BPD. 

PMID- 25858802
TI  - Combatting bacterial infections by killing persister cells with mitomycin C.
AB  - Persister cells are a multi-drug tolerant subpopulation of bacteria that
      contribute to chronic and recalcitrant clinical infections such as cystic
      fibrosis and tuberculosis. Persisters are metabolically dormant, so they are
      highly tolerant to all traditional antibiotics which are mainly effective against
      actively growing cells. Here, we show that the FDA-approved anti-cancer drug
      mitomycin C (MMC) eradicates persister cells through a growth-independent
      mechanism. MMC is passively transported and bioreductively activated, leading to
      spontaneous cross-linking of DNA, which we verify in both active and dormant
      cells. We find MMC effectively eradicates cells grown in numerous different
      growth states (e.g. planktonic cultures and highly robust biofilm cultures) in
      both rich and minimal media. Additionally, MMC is a potent bactericide for a
      broad range of bacterial persisters, including commensal Escherichia coli K-12 as
      well as pathogenic species of E. coli, Staphylococcus aureus and Pseudomonas
      aeruginosa. We also demonstrate the efficacy of MMC in an animal model and a
      wound model, substantiating the clinical applicability of MMC against bacterial
      infections. Therefore, MMC is the first broad-spectrum compound capable of
      eliminating persister cells, meriting investigation as a new approach for the
      treatment of recalcitrant infections. 

PMID- 25858803
TI  - The journey from discoveries in fundamental immunology to cancer immunotherapy.
AB  - Recent advances in cancer immunotherapy have directly built on 50 years of
      fundamental and technological advances that made checkpoint blockade and T cell
      engineering possible. In this review, we intend to show that research, not
      specifically designed to bring relief or cure to any particular disease, can,
      when creatively exploited, lead to spectacular results in the management of
      cancer. The discovery of thymus immune function, T cells, and immune surveillance
      bore the seeds for today's targeted immune interventions and chimeric antigen
      receptors. 

PMID- 25858804
TI  - Immune checkpoint blockade: a common denominator approach to cancer therapy.
AB  - The immune system recognizes and is poised to eliminate cancer but is held in
      check by inhibitory receptors and ligands. These immune checkpoint pathways,
      which normally maintain self-tolerance and limit collateral tissue damage during
      anti-microbial immune responses, can be co-opted by cancer to evade immune
      destruction. Drugs interrupting immune checkpoints, such as anti-CTLA-4, anti-PD
      1, anti-PD-L1, and others in early development, can unleash anti-tumor immunity
      and mediate durable cancer regressions. The complex biology of immune checkpoint
      pathways still contains many mysteries, and the full activity spectrum of
      checkpoint-blocking drugs, used alone or in combination, is currently the subject
      of intense study. 

PMID- 25858805
TI  - Macrophages and therapeutic resistance in cancer.
AB  - How neoplastic cells respond to therapy is not solely dependent on the complexity
      of the genomic aberrations they harbor but is also regulated by numerous dynamic
      properties of the tumor microenvironment. Identifying and targeting critical
      pathways that improve therapeutic efficacy by bolstering anti-tumor immune
      responses holds great potential for improving outcomes and impacting long-term
      patient survival. Macrophages are key regulators of homeostatic tissue and tumor
      microenvironments. Therefore, therapeutics impacting macrophage presence and/or
      bioactivity have shown promise in preclinical models and are now being evaluated
      in the clinic. This review discusses the molecular/cellular pathways identified
      so far whereby macrophages mediate therapeutic responses. 

PMID- 25858808
TI  - The contradictions of homeopathy legislation.

PMID- 25858806
TI  - Health behavior change following a diagnosis of ductal carcinoma in situ: An
      opportunity to improve health outcomes.
AB  - Ductal carcinoma in situ (DCIS) is a non-invasive breast cancer that comprises
      approximately 20% of new breast cancer diagnoses. DCIS is predominantly detected
      by screening mammography prior to the development of any clinical symptoms.
      Prognosis following a DCIS diagnosis is excellent, due to both the availability
      of effective treatments and the frequently benign nature of the disease. However,
      a DCIS diagnosis and its treatment have psychological and physical impacts that
      often lead to adverse changes in health-related behaviors, including changes in
      physical activity, body weight, alcohol intake, and smoking, which may represent
      a greater threat to the woman's overall health than the DCIS itself. Depending on
      age at diagnosis, women diagnosed with DCIS are 3-13 times more likely to die
      from non-breast cancer related causes, such as cardiovascular disease, than from
      breast cancer. Thus, the maintenance and improvement of healthy behaviors that
      influence a variety of outcomes after diagnosis may warrant increased attention
      during DCIS management. This may also represent an important opportunity to
      promote the adoption of healthy behaviors, given that DCIS carries the
      psychological impact of a cancer diagnosis but also a favorable prognosis.
      Particular focus is needed to address these issues in vulnerable patient
      subgroups with pre-existing higher rates of unhealthy behaviors and demonstrated
      health disparities. 

PMID- 25858807
TI  - Regulation of autophagy and the ubiquitin-proteasome system by the FoxO
      transcriptional network during muscle atrophy.
AB  - Stresses like low nutrients, systemic inflammation, cancer or infections provoke
      a catabolic state characterized by enhanced muscle proteolysis and amino acid
      release to sustain liver gluconeogenesis and tissue protein synthesis. These
      conditions activate the family of Forkhead Box (Fox) O transcription factors.
      Here we report that muscle-specific deletion of FoxO members protects from muscle
      loss as a result of the role of FoxOs in the induction of autophagy-lysosome and
      ubiquitin-proteasome systems. Notably, in the setting of low nutrient signalling,
      we demonstrate that FoxOs are required for Akt activity but not for mTOR
      signalling. FoxOs control several stress-response pathways such as the unfolded
      protein response, ROS detoxification, DNA repair and translation. Finally, we
      identify FoxO-dependent ubiquitin ligases including MUSA1 and a previously
      uncharacterised ligase termed SMART (Specific of Muscle Atrophy and Regulated by
      Transcription). Our findings underscore the central function of FoxOs in
      coordinating a variety of stress-response genes during catabolic conditions. 

PMID- 25858809
TI  - Age-related and obstacle height-related differences in movements while stepping
      over obstacles.
AB  - BACKGROUND: This study aims to examine age-related and obstacle height-related
      differences in movements while stepping over obstacles. METHODS: The participants
      included 16 elderly and nine young women. Obstacles that were either 5 or 20 cm
      high were positioned at the center of a 4-m walking path. The participants were
      instructed to walk along the path as quickly as possible. The participants'
      movements were analyzed using a three-dimensional motion analysis system that
      recorded their movements as they walked and stepped over the obstacles. RESULTS
      AND CONCLUSIONS: Seven joint angles and the distances between the ground and six
      markers were examined in the initial contact and swing instants of the leading
      and trailing limbs. In the initial contact instant, the elderly women prepared
      for stepping with a lower toe height than the young women when stepping over the
      20-cm obstacle. Trunk rotation was greater in the young women than in the elderly
      women. In the swing instant, the elderly women showed greater ankle dorsiflexion
      and hip adduction angles for the leading limb when stepping over the 20-cm
      obstacle. They moved the trailing limb with increased ankle dorsiflexion, knee
      flexion, hip flexion, and foot inversion to ensure that they did not touch the
      obstacle as they stepped over it. These movement patterns are characteristic of
      elderly individuals who cannot easily lift their lower limbs because of decreased
      lower-limb strength.

PMID- 25858811
TI  - Smart design of fiber optic surfaces for improved plasmonic biosensing.
AB  - Although the phenomenon of surface plasmon resonance (SPR) is known for more than
      a century now, traditional prism-based SPR platforms have hardly escaped the
      research laboratories despite being recognized for the sensitive and specific
      performance. Significant efforts have been made over the last years to overcome
      their existing limitations by coupling the SPR phenomenon to the fiber optic (FO)
      technology. While this platform has been promoted as cost-effective and simpler
      alternative capable of handling label-free bioassays, quantification and real
      time monitoring of biomolecular interactions, examples of its applicability in
      sensing and biosensing remain to date very limited. The FO-SPR system is still in
      development and requires further advancements for reaching the stability and
      sensitivity of the benchmark SPR systems. Among existing strategies for device
      improvement, those based on modifying the FO tips using nanomaterials are mostly
      studied. These small-scale objects provide a wide range of possibilities for
      alternating the architecture of the FO sensitive zone, enabling also unique
      effects such as localized SPR (LSPR). This mini-review summarizes the latest
      innovations in the fabrication procedures which use nanoparticles or other
      nanomaterials, aiming at FO-SPR technology performance improvements, as well as
      addition of new device features and functionalities. 

PMID- 25858810
TI  - Induction Therapy with Bortezomib Followed by Bortezomib-High Dose Melphalan and
      Stem Cell Transplantation for Light Chain Amyloidosis: Results of a Prospective
      Clinical Trial.
AB  - The depth of hematologic response has been shown to correlate with survival and
      organ responses for patients with light chain (AL) amyloidosis. We conducted a
      prospective trial of 2 cycles of induction with bortezomib and dexamethasone on a
      twice a week schedule followed by conditioning with bortezomib and high-dose
      melphalan (HDM) and autologous stem cell transplantation (SCT). The objectives
      were hematologic responses, tolerability, and survival. Thirty-five patients were
      enrolled from 2010 to 2013. Of these, 30 proceeded with SCT, whereas 5 did not
      because of clinical deterioration during induction (n = 3) or complications after
      stem cell collection (n = 2). Two patients developed features of an autologous
      graft-versus-host disease-like syndrome post-SCT, which responded to steroids; no
      other unusual complications were seen. Treatment-related mortality occurred in
      8.5% (3/35). Hematologic responses were achieved by 100% of the 27 assessable
      patients (63% complete response, 37% very good partial response [VGPR]) who
      completed the planned treatment. By intention-to-treat, hematologic responses
      occurred in 77% of patients (49% complete response, 29% VGPR). With a median
      follow-up of 36 months, the median overall survival and progression-free survival
      were not reached. In conclusion, incorporating bortezomib into induction and
      conditioning yielded a high rate of hematologic responses after HDM/SCT in
      patients with AL amyloidosis.

PMID- 25858812
TI  - Multiplexed detection of foodborne pathogens based on magnetic particles.
AB  - This paper addresses the novel approaches for the multiplex detection of food
      poisoning bacteria, paying closer attention to three of the most common pathogens
      involved in food outbreaks: Salmonella enterica, Escherichia coli O157:H7 and
      Listeria monocytogenes. End-point and real-time PCR, classical immunological
      techniques, biosensors, microarrays and microfluidic platforms, as well as
      commercial kits for multiplex detection of food pathogens will be reviewed, with
      special focus on the role of magnetic particles in these approaches. Although the
      immunomagnetic separation for capturing single bacteria from contaminating
      microflora and interfering food components has demonstrated to improve the
      performance on these approaches, the integration of magnetic particles for
      multiplex detection of bacteria is still in a preliminary stage and requires
      further studies. 

PMID- 25858813
TI  - Kallikrein-related peptidases targeted therapies in prostate cancer: perspectives
      and challenges.
AB  - INTRODUCTION: Despite the emergence of several new effective treatments for
      metastatic castration-resistant prostate cancer patients, disease progression
      inevitably occurs, leading scientific community to carefully look for novel
      therapeutic targets of prostate cancer. Kallikrein (KLK)-related peptidases have
      been demonstrated to facilitate prostate tumorigenesis and disease progression
      through the development of an oncogenic microenvironment for prostate cells.
      AREAS COVERED: This review first summarizes the large amount of preclinical data
      showing the involvement of KLKs in prostate cancer pathobiology. In the second
      part, the authors assess the current status and future directions for KLK
      targeted therapy and briefly describe the advances and challenges implicated in
      the design of effective manufactured drugs. The authors then focus on the
      preclinical data and on Phase I/II studies of the most promising KLK-targeted
      agents in prostate cancer. The drugs discussed here are divided on the basis of
      their mechanism of action: KLK-engineered inhibitors; KLK-activated pro-drugs;
      KLK-targeted microRNAs and small interfering RNAs(-/)small hairpin RNAs; KLK
      vaccines and antibodies. EXPERT OPINION: Targeting KLK expression and/or activity
      could be a promising direction in prostate cancer treatment. Future human
      clinical trials will help us to evaluate the real benefits, toxicities and the
      consequent optimal use of KLK-targeted drugs, as mono-therapy or in combination
      regimens.

PMID- 25858814
TI  - A randomized clinical trial evaluating metabolism of colostral and plasma derived
      immunoglobulin G in Jersey bull calves.
AB  - BACKGROUND: Intravenous plasma administration has been recommended in healthy or
      sick calves with failure of passive immunity. HYPOTHESIS: IV administered plasma
      derived immunoglobulin G (IgG) undergoes increased catabolism as reflected by a
      rapid decrease in serum IgG concentration with an increase in fecal IgG
      concentrations within 48 h. ANIMALS: Thirty newborn Jersey calves. Fifteen were
      fed colostrum (CL group) and 15 were given bovine plasma IV (PL group). MATERIALS
      AND METHODS: Randomized clinical trial. Calves in the CL group were fed 3 L of
      colostrum once, by oroesophageal tubing. Calves in the PL group were given plasma
      IV at a dosage of 34 mL/kg. Serum and fecal samples were collected at 0 h, 6 h,
      12 h, 48 h, 5 d, and 7 d. Serum and fecal IgG concentrations were determined by
      radial immunodiffusion. RESULTS: Calves in the CL group maintained serum IgG
      concentrations consistent with adequate transfer of immunity (>=1,000 mg/dL)
      throughout the study period. Calves in the PL group achieved median IgG
      concentrations of >=1,000 mg/dL at 6 h but the concentrations were <1,000 mg/dL
      by 12 h. Calves in the PL group were 5 times more likely to experience mortality
      compared to the CL group (hazard ratio = 5.01). Fecal IgG concentrations were not
      different between the 2 groups during the first 48 h (P > .05). CONCLUSIONS AND
      CLINICAL IMPORTANCE: Catabolism of plasma derived IgG occurs rapidly during the
      first 12 h after transfusion. Fecal excretion did not explain the fate of the
      plasma derived IgG.

PMID- 25858816
TI  - NHS prescription charges.
AB  - In 2009, DTB published an editorial calling for the abolition of the NHS
      prescription charge.1 The article highlighted that from April 2011, England would
      be the only UK country that would tax patients for medicines through levying a
      prescription charge. In addition, it noted that the categorisation of medical and
      other exemptions is illogical and that the prescription charge is a poorly
      conceived, manifestly unfair tax. Of particular concern is the impact of the
      prescription charge on patients with chronic conditions that do not fall into the
      exemption categories. For many years the Prescription Charges Coalition, an
      alliance of more than 30 organisations concerned with the impact of prescription
      charges on people with long-term conditions, has campaigned to extend exemption
      from prescription charges to all those with long-term conditions.2 A subsequent
      DTB editorial, published in 2014, discussed anomalies associated with the
      prescription charge, including the cost of administering the bureaucracy needed
      to underpin the collection and checking of exemptions, and management of pre
      payment certification.3 The editorial repeated the call for prescription charges
      to be abolished. Revisiting these themes, here we present an overview of the
      results of a survey conducted to explore the views of healthcare professionals on
      the NHS prescription charge. 

PMID- 25858815
TI  - ?Olodaterol--another LABA for COPD.
AB  - ?Olodaterol solution for inhalation (Striverdi Respimat-Boehringer Ingelheim) is
      a long-acting beta2 agonist (LABA) licensed for once-daily use as maintenance
      bronchodilator therapy for chronic obstructive pulmonary disease (COPD). This is
      the third LABA to be licensed in the UK for once-daily use for patients with
      COPD. DTB has previously reviewed the use of indacaterol and vilanterol in
      combination with fluticasone furoate (?Relvar Ellipta).1,2 In this article we
      consider the evidence for olodaterol and whether it offers any advantages in the
      management of COPD. 

PMID- 25858817
TI  - X-ray Study of Human Dental Tissues Affected by Erythroblastosis Fetalis.
AB  - Numerous diseases are known to cause microstructural alteration of dental tissues
      structure. One type in particular is associated with neonatal jaundice and
      circulation of bilirubin in blood at high concentration due to increased
      hemolysis in conditions such as erythroblastosis fetalis, septicemia, biliary
      atresia, and other causes of hyperbilirubinemia. In those conditions, the
      products of the catabolism of hemoglobin end up deposited in various tissues,
      including teeth, where they can present clinically as visibly stained brown/green
      teeth. There is almost no information on the nature or extent of the structural
      changes taking place in these conditions. Here, advanced nondestructive wide
      angle synchrotron X-ray scattering techniques combined with scanning microscopy
      methods were used to investigate for the first time the ultrastructure of the
      dental hard tissues in an archival case of intrinsically pigmented green teeth.
      Despite no obvious elemental variation across the pigmented tissue region, the
      high-resolution crystallographic properties probed by wide-angle synchrotron X
      ray scattering revealed an ultrastructural variation (orientation, particle size,
      and lattice parameter of hydroxyapatite crystallites) associated with a
      pigmentation line in dentine and with a distinct neonatal line in enamel. 

PMID- 25858818
TI  - NADPH Oxidase 4 Mediates TGFbeta1-induced CCN2 in Gingival Fibroblasts.
AB  - Transforming growth factor beta (TGFbeta) plays a central role in the
      pathogenesis of gingival overgrowth (GO). Connective tissue growth factor (CTGF;
      or CCN2) is induced by TGFbeta in human gingival fibroblasts (HGFs) and is
      overexpressed in GO tissues. CCN2 creates an environment favorable for
      fibrogenesis and is required for the maximal profibrotic effects of TGFbeta. We
      previously showed that Src, JNK, and Smad3 mediate TGFbeta1-induced CCN2 protein
      expression in HGFs. Moreover, Src is an upstream signaling transducer of JNK and
      Smad3. Recent studies suggested that NADPH oxidase (NOX)-dependent redox
      mechanisms are involved in mediating the profibrotic effects of TGFbeta. In this
      study, we demonstrated that TGFbeta1 upregulated NOX4 protein expression and
      increased reactive oxygen species (ROS) production in HGFs. Genetic or
      pharmacologic targeting of NOX4 abrogated TGFbeta1-induced ROS production; Src,
      JNK, and Smad3 activation; and CCN2 and type I collagen protein expression in
      HGFs. Our results indicated that NOX4-derived ROS play pivotal roles in
      activating Src kinase activity leading to the activation of canonical (Smad3) and
      noncanonical (JNK) cascades that cooperate to attain maximum CCN2 expression.
      Furthermore, we demonstrated that curcumin significantly inhibited the TGFbeta1
      induced NOX4 protein expression in HGFs. Curcumin potentially qualifies as an
      agent to control GO by suppressing TGFbeta1-induced NOX4 expression in HGFs. 

PMID- 25858819
TI  - Femoral venous oxygen saturation and central venous oxygen saturation in
      critically ill patients.
AB  - OBJECTIVES: To investigate the relationship between central venous oxygen
      saturation (ScvO(2)) and femoral venous oxygen saturation (SfvO(2)) in a large
      group of critically ill patients. DESIGN: Observational study. PATIENTS: A group
      of unselected critically ill patients with central line placed into superior vena
      cava were included. SETTING: A 26-bed intensive care unit in a tertiary referral
      hospital. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Venous blood
      samples of superior vena cava and femoral vein were collected within an interval
      of 5 to 15 minutes and analyzed with blood gas/electrolyte analyzer immediately.
      Although SfvO(2) was significantly correlated with ScvO(2) (r = 0.493, P < .001;
      Pearson correlation, 2 tailed), the limits of agreement were wide (up to 61% to 
      41%) between the 731 pairs of blood samples collected from 357 patients. The fit
      line of scatter diagram ScvO(2) vs SfvO(2) had a large intercept (48.68%) and a
      low slope (0.2978); ScvO(2) was still around 50% while SfvO(2) was nearing 0%.
      The distribution of blood flow, measured with Doppler ultrasound, had a similar
      trend in 237 patients and 412 measurements. The ratio of femoral artery flow over
      common carotid artery flow varied widely (from 0 to 7.13). Blood flow was not
      distributed in a fixed ratio to the superior vena cava-drained organs and
      tissues. CONCLUSIONS: Central venous oxygen saturation was not representative of
      the whole systemic circulation in critically ill patients. Central venous oxygen
      saturation alone might be misleading in goal-directed therapy.

PMID- 25858820
TI  - Sample entropy predicts lifesaving interventions in trauma patients with normal
      vital signs.
AB  - INTRODUCTION: Heart rate complexity, commonly described as a "new vital sign,"
      has shown promise in predicting injury severity, but its use in clinical practice
      is not yet widely adopted. We previously demonstrated the ability of this
      noninvasive technology to predict lifesaving interventions (LSIs) in trauma
      patients. This study was conducted to prospectively evaluate the utility of real
      time, automated, noninvasive, instantaneous sample entropy (SampEn) analysis to
      predict the need for an LSI in a trauma alert population presenting with normal
      vital signs. METHODS: Prospective enrollment of patients who met criteria for
      trauma team activation and presented with normal vital signs was conducted at a
      level I trauma center. High-fidelity electrocardiogram recording was used to
      calculate SampEn and SD of the normal-to-normal R-R interval (SDNN) continuously
      in real time for 2 hours with a portable, handheld device. Patients who received
      an LSI were compared to patients without any intervention (non-LSI).
      Multivariable analysis was performed to control for differences between the
      groups. Treating clinicians were blinded to results. RESULTS: Of 129 patients
      enrolled, 38 (29%) received 136 LSIs within 24 hours of hospital arrival. Initial
      systolic blood pressure was similar in both groups. Lifesaving intervention
      patients had a lower Glasgow Coma Scale. The mean SampEn on presentation was 0.7
      (0.4-1.2) in the LSI group compared to 1.5 (1.1-2.0) in the non-LSI group (P <
      .0001). The area under the curve with initial SampEn alone was 0.73 (95%
      confidence interval [CI], 0.64-0.81) and increased to 0.93 (95% CI, 0.89-0.98)
      after adding sedation to the model. Sample entropy of less than 0.8 yields
      sensitivity, specificity, negative predictive value, and positive predictive
      value of 58%, 86%, 82%, and 65%, respectively, with an overall accuracy of 76%
      for predicting an LSI. SD of the normal-to-normal R-R interval had no predictive
      value. CONCLUSIONS: In trauma patients with normal presenting vital signs,
      decreased SampEn is an independent predictor of the need for LSI. Real-time
      SampEn analysis may be a useful adjunct to standard vital signs monitoring.
      Adoption of real-time, instantaneous SampEn monitoring for trauma patients,
      especially in resource-constrained environments, should be considered.

PMID- 25858821
TI  - Polymorphisms in folate pathway genes are not associated with somatic
      nondisjunction in turner syndrome.
AB  - Folate metabolism dysfunction can lead to DNA hypomethylation and abnormal
      chromosomal segregation. Previous investigations of this association have
      produced controversial results. Here we performed a case-control study in
      patients with Turner syndrome (TS) to determine the effects of genetic
      polymorphisms of folate pathway genes as potential risk factors for somatic
      chromosomal nondisjunction. TS is a useful model for this investigation because
      patients with TS show a high frequency of chromosome mosaicism. Here we
      investigated the possible association of polymorphisms of the MTHFR gene with TS
      risk, which has been previously investigated with controversial results. We also
      examined the effects of MTR, RFC1, and TYMS gene polymorphisms in TS for the
      first time. The risk was evaluated according to allelic and genotype (independent
      and combined) frequencies among 70 patients with TS and 144 age-matched healthy
      control subjects. Polymorphism genotyping was performed by PCR, PCR-RFLP, and PCR
      ASA. The polymorphisms MTHFR 677C>T and 1298A>C, MTR 2756A>G, RFC1 80G>A, and
      TYMS 2R/3R-alone or in combinations-were not associated with the risk of
      chromosomal aneuploidy in TS. In conclusion, our present findings did not support
      a link between impaired folate metabolism and abnormal chromosome segregation
      leading to somatic nondisjunction in TS patients.

PMID- 25858822
TI  - Complete Genome Sequences of vB_LmoS_188 and vB_LmoS_293, Two Bacteriophages with
      Specificity for Listeria monocytogenes Strains of Serotypes 4b and 4e.
AB  - Listeria monocytogenes is responsible for the rare disease listeriosis, which is
      associated with the consumption of contaminated food products. We report here the
      complete genome sequences of vB_LmoS_188 and vB_LmoS_293, phages isolated from
      environmental sources and that have host specificity for L. monocytogenes strains
      of the 4b and 4e serotypes. 

PMID- 25858823
TI  - Genome Sequence of Bluetongue Virus Type 2 from India: Evidence for Reassortment
      between Outer Capsid Protein Genes.
AB  - Southern Indian isolate IND1994/01 of bluetongue virus serotype 2 (BTV-2), from
      the Orbivirus Reference Collection at the Pirbright Institute
      (http://www.reoviridae.org/dsRNA_virus_proteins/ReoID/btv-2.htm#IND1994/01), was
      sequenced. Its genome segment 6 (Seg-6) [encoding VP5(OCP2)] is identical to that
      of the Indian BTV-1 isolate (IND2003/05), while Seg-5 and Seg-9 are closely
      related to isolates from South Africa and the United States, respectively. 

PMID- 25858824
TI  - Rethinking the Niche of Upper-Atmosphere Bacteria: Draft Genome Sequences of
      Bacillus aryabhattai C765 and Bacillus aerophilus C772, Isolated from Rice
      Fields.
AB  - Here, we report two genome sequences of endospore-forming bacteria isolated from
      the rice fields of Comporta, Portugal, identified as Bacillus aryabhattai C765
      and Bacillus aerophilus C772. Both species were previously identified in air
      samples from the upper atmosphere, but our findings suggest their presence in a
      wider range of environmental niches. 

PMID- 25858825
TI  - Complete Genome Sequence of Mannheimia haemolytica Strain Mh10517, Isolated from
      Sheep in South Africa.
AB  - Respiratory disease caused by Mannheimia haemolytica is a major concern in the
      cattle and small stock industry worldwide. This problem arises due to the
      interaction of numerous contributing factors, including physical stresses
      associated with weaning, shipment, inclement weather, and overcrowding coupled
      with viral and bacterial infections. The whole genome of M. haemolytica strain
      Mh10517 was analyzed using an Illumina MiSeq high-throughput sequencing platform.
      The genome size is 2.67 Mb with 2,879 predicted gene sequences. The availability
      of this genome sequence will advance studies on various aspects of the biology of
      M. haemolytica in Africa and the world at large. 

PMID- 25858826
TI  - Draft Genome Sequences of Supercritical CO2-Tolerant Bacteria Bacillus
      subterraneus MITOT1 and Bacillus cereus MIT0214.
AB  - We report draft genome sequences of Bacillus subterraneus MITOT1 and Bacillus
      cereus MIT0214 isolated through enrichment of samples from geologic sequestration
      sites in pressurized bioreactors containing a supercritical (sc) CO2 headspace.
      Their genome sequences expand the phylogenetic range of sequenced bacilli and
      allow characterization of molecular mechanisms of scCO2 tolerance. 

PMID- 25858827
TI  - Complete Genome Sequence of Salmonella enterica Serovar Typhimurium Myophage
      Mushroom.
AB  - Salmonella enterica serovar Typhimurium (S. Typhimurium) is a leading cause of
      foodborne illness worldwide. Over the past two decades, strains resistant to
      antibiotics have begun to emerge, highlighting the need for alternative treatment
      strategies such as bacteriophage therapy. Here, we present the complete genome of
      Mushroom, an S. Typhimurium myophage. 

PMID- 25858828
TI  - Identification of a Genotype VIId Newcastle Disease Virus Isolated from Sansui
      Sheldrake Ducks in Guizhou Province, China.
AB  - In this study, we report the complete genome sequence of a novel Newcastle
      disease virus (NDV) strain, Sheldrake duck/China/Guizhou/SS1/2014, isolated from
      Sansui Sheldrake duck flocks in Guizhou Province, southwestern China. The genome
      of this isolate is 15,192 nucleotides in length, which belongs to NDV genotype
      VIId in class II. This discovery will help us further study the epidemiology
      characteristics and molecular pathogenesis of genotype VIId NDV in Sansui
      Sheldrake ducks. 

PMID- 25858829
TI  - Complete Genome Sequence of Lactobacillus acidophilus FSI4, Isolated from Yogurt.
AB  - A new Lactobacillus acidophilus strain, FSI4, isolated from yogurt, was isolated
      and sequenced in our laboratory. Our data, although supportive of previous
      conclusions regarding the remarkable stability of L. acidophilus species,
      indicate accumulating mutations in commercial L. acidophilus strains that warrant
      further study of the effect of damaged genes on the competitiveness of these
      bacteria in gut microbiota. 

PMID- 25858830
TI  - De Novo Whole-Genome Sequence of Micromonospora carbonacea JXNU-1 with Broad
      Spectrum Antimicrobial Activity, Isolated from Soil Samples.
AB  - Micromonospora carbonacea JXNU-1 is an actinomycete with broad-spectrum
      antimicrobial activity, isolated from soil samples from the farmland in the area
      of Yaohu Lake in Nanchang, China. Here, we report the whole-genome sequence of M.
      carbonacea JXNU-1. 

PMID- 25858831
TI  - Genome Sequence of a Pseudomonas syringae pv. tabaci Strain, yuexi-1, Causing
      Wildfire Disease in Tobacco.
AB  - We determined the draft genome sequence of the Pseudomonas syringae pv. tabaci
      strain yuexi-1. It was isolated from tobacco sample of yuexi-1, Sichuan province,
      China, by our laboratory. The genome contains 6,232,497 bp and has a G+C content
      of 58.2 mol%. 

PMID- 25858832
TI  - Draft genome sequences of 26 porphyromonas strains isolated from the canine oral
      microbiome.
AB  - We present the draft genome sequences for 26 strains of Porphyromonas (P.
      canoris, P. gulae, P. cangingavalis, P. macacae, and 7 unidentified) and an
      unidentified member of the Porphyromonadaceae family. All of these strains were
      isolated from the canine oral cavity, from dogs with and without early
      periodontal disease. 

PMID- 25858833
TI  - Draft Genome Sequence of NDM-5-Producing Escherichia coli Sequence Type 648 and
      Genetic Context of blaNDM-5 in Australia.
AB  - We report here the draft genome sequence of uropathogenic Escherichia coli
      sequence type 648 (ST648) possessing blaNDM-5 from a 55-year-old female in
      Australia with a history of travel to India. The plasmid-mediated blaNDM-5 was in
      a genetic context nearly identical to that of the GenBank entry of an IncX3
      blaNDM-5 plasmid previously reported from India (Klebsiella pneumoniae MGR-K194).

PMID- 25858834
TI  - Draft Genome Sequence of Rhodotorula mucilaginosa, an Emergent Opportunistic
      Pathogen.
AB  - Rhodotorula mucilaginosa, a yeast with valuable biotechnological features, has
      also been recorded as an emergent opportunistic pathogen that might cause disease
      in both immunocompetent and immunocompromised individuals. Here, we report the
      draft genome sequence of R. mucilaginosa strain C2.5t1, which was isolated from
      cacao seeds in Cameroon. 

PMID- 25858835
TI  - Draft Genome Sequence of Exophiala mesophila, a Black Yeast with High
      Bioremediation Potential.
AB  - The fungal genus Exophiala comprises both pathogen species, which cause severe
      infections in humans, and environmental species, which are able to degrade
      alkylbenzene compounds. The draft genome sequence of Exophiala mesophila
      presented here is the first genome assembly of an alkylbenzene-degrading organism
      belonging to the genus Exophiala. 

PMID- 25858836
TI  - Genome Sequence of EU-Unauthorized Genetically Modified Bacillus subtilis Strain
      2014-3557 Overproducing Riboflavin, Isolated from a Vitamin B2 80% Feed Additive.
AB  - This paper announces the genome sequence and annotation of the genetically
      modified (GM) Bacillus subtilis strain 2014-3557 overproducing riboflavin
      (vitamin B2). This GM-strain is unauthorized in the European Union. Nevertheless,
      it has been isolated from a lot of vitamin B2 (riboflavin) 80% feed grade
      imported to Europe from China. 

PMID- 25858837
TI  - Draft Genome Sequences for Canadian Isolates of Pectobacterium carotovorum subsp.
      brasiliense with Weak Virulence on Potato.
AB  - Pectobacterium carotovurum subsp. brasiliense causes soft rot and blackleg
      diseases on potato. Here, we report the draft genome sequences of three weakly
      virulent P. carotovurum subsp. brasiliense strains isolated in Canada. Analysis
      of these genome sequences will help to pinpoint differences in virulence among P.
      carotovurum subsp. brasiliense strains from tropical/subtropical and temperate
      regions, such as Canada and United States. A small number of key factors for
      adaptation to this bacterium's specific environmental niche were also evaluated. 

PMID- 25858838
TI  - Draft Genome Sequence of a Helicobacter pylori Strain Isolated from a Patient
      with Diffuse Gastritis from a Region of High Cancer Risk in Colombia.
AB  - The draft genome sequence of one Colombian Helicobacter pylori strain is
      presented. This strain was isolated from a patient with diffuse gastritis from
      Tibana, Boyaca, a region with high gastric cancer risk. 

PMID- 25858839
TI  - Complete Genome Sequence of a Novel Bacterium within the Family Rhodocyclaceae
      That Degrades Polycyclic Aromatic Hydrocarbons.
AB  - A polycyclic aromatic hydrocarbon-degrading bacterium designated strain Ca6, a
      member of the family Rhodocyclaceae and a representative of the uncharacterized
      pyrene group 1 (PG1), was isolated and its genome sequenced. The presence of
      several genes suspected to be associated with PG1 was confirmed, and additional
      genes for aromatic compound metabolism were detected. 

PMID- 25858840
TI  - Draft Genome Sequence of Shewanella sp. Strain CP20.
AB  - Shewanella sp. CP20 is a marine bacterium that survives ingestion by Tetrahymena
      pyriformis and is expelled from the protozoan within membrane-bound vacuoles,
      where the bacterial cells show long-term survival. Here, we report the draft
      genome sequence of Shewanella sp. CP20 and discuss the potential mechanisms
      facilitating intraprotozoan survival. 

PMID- 25858841
TI  - Genome Sequences of Two Bovine Mastitis-Causing Escherichia coli Strains.
AB  - Escherichia coli is one of the main pathogenic agents causing inflammatory
      infections in the bovine udder. Here, we report the draft genome sequences of two
      strains isolated from different cases of clinical mastitis. 

PMID- 25858842
TI  - Complete Genome Sequence of Methylobacterium aquaticum Strain 22A, Isolated from
      Racomitrium japonicum Moss.
AB  - Methylobacterium species colonize plant surfaces and utilize methanol emitted
      from plants. Methylobacterium aquaticum strain 22A was isolated from a hydroponic
      culture of a moss, Racomitrium japonicum, and is a potent plant growth promoter.
      The complete genome sequencing of the strain confirmed the presence of genes
      related to plant growth promotion and methylotrophy. 

PMID- 25858843
TI  - Draft Genome Sequence of the Piezotolerant and Crude Oil-Degrading Bacterium
      Rhodococcus qingshengii Strain TUHH-12.
AB  - We report here the draft genome sequence of Rhodococcus qingshengii strain TUHH
      12. The ability of this piezotolerant bacterium to grow on crude oil and
      tetracosane as sole carbon sources at 150 * 10(5) Pa makes it useful in studies
      of hydrocarbon degradation under simulated deep-sea conditions. 

PMID- 25858844
TI  - Complete Genome Sequence of a Carbapenem-Resistant Extraintestinal Pathogenic
      Escherichia coli Strain Belonging to the Sequence Type 131 H30R Subclade.
AB  - Here, we report the completed genome sequence of a carbapenem-resistant
      extraintestinal pathogenic Escherichia coli sequence type 131 (ST131) isolate,
      MNCRE44. The isolate was obtained in 2012 in Minnesota, USA, from a sputum sample
      from a hospitalized patient with multiple comorbidities, and it belongs to the
      H30R sublineage. 

PMID- 25858845
TI  - Draft Genome Sequence of Klebsiella pneumoniae Carbapenemase-Producing
      Acinetobacter baumannii Strain M3AC9-7, Isolated from Puerto Rico.
AB  - We report the draft genome of a multidrug resistant, Klebsiella pneumoniae
      carbapenemase (KPC)-producing Acinetobacter baumannii strain M3AC9-7 that belongs
      to the novel sequence type, ST250. The draft genome consists of a total length of
      4.09 Mbp and a G+C content of 38.95%. 

PMID- 25858846
TI  - Genome Resequencing of the Virulent and Multidrug-Resistant Reference Strain
      Clostridium difficile 630.
AB  - We resequenced the complete genome of the virulent and multidrug-resistant
      pathogen Clostridium difficile strain 630. A combination of single-molecule real
      time and Illumina sequencing technology revealed the presence of an additional
      rRNA gene cluster, additional tRNAs, and the absence of a transposon in
      comparison to the published and reannotated genome sequence. 

PMID- 25858847
TI  - Complete Genome Sequence of Bifidobacterium dentium Strain JCM 1195T, Isolated
      from Human Dental Caries.
AB  - Bifidobacterium dentium strain JCM 1195(T) was isolated from human dental caries.
      Here, we report the complete genome sequence of this organism. 

PMID- 25858848
TI  - Complete Genome Sequence of Bifidobacterium scardovii Strain JCM 12489T, Isolated
      from Human Blood.
AB  - Bifidobacterium scardovii strain JCM 12489(T) was isolated from human blood and
      has the largest bifidobacterial genome reported to date. Here, we report the
      complete genome sequence of this organism. This paper is the first report
      demonstrating the fully sequenced and completely annotated genome of a B.
      scardovii strain. 

PMID- 25858849
TI  - Complete Genome Sequence of Gardnerella vaginalis Strain JCM 11026T, Isolated
      from Vaginal Tracts of Women.
AB  - Gardnerella vaginalis strain JCM 11026(T) was isolated from vaginal tracts of
      women. Here, we report the complete genome sequence of this organism. 

PMID- 25858850
TI  - Draft Genome Sequence of the First Hypermucoviscous Klebsiella variicola Clinical
      Isolate.
AB  - An antibiotic-susceptible and hypermucoviscous clinical isolate of Klebsiella
      variicola (K. variicola 8917) was obtained from the sputum of an adult patient.
      This work reports the complete draft genome sequence of K. variicola 8917 with
      103 contigs and an annotation that revealed a 5,686,491-bp circular chromosome
      containing a total of 5,621 coding DNA sequences, 65 tRNA genes, and an average
      G+C content of 56.98%. 

PMID- 25858851
TI  - Complete genome sequence of an american avian leukosis virus subgroup j isolate
      that causes hemangiomas and myeloid leukosis.
AB  - We report the complete genome sequence of avian leukosis virus subgroup J (ALV-J)
      isolate PDRC-59831, which causes myeloid leukosis and hemangiomas in chickens.
      This is an American ALV-J isolate, which was found in a 38-week-old broiler
      breeder chicken on a farm in Georgia in 2007. 

PMID- 25858852
TI  - Changes of gene expression of Gal3, Hsp27, Lcn2, and Timp1 in rat substantia
      nigra following medial forebrain bundle transection using a candidate gene
      microarray.
AB  - Neuroinflammation is an early event and important contributor to the pathobiology
      of neurodegenerative diseases. Neuroglia, especially microglia, are a major
      central nervous system population that can modulate neuroinflammation. To
      determine potential key molecules in this process, we employed microarray
      analysis in the substantia nigra (SN) following medial forebrain bundle (MFB)
      transection and analyzed the temporal expression profiles of candidate genes
      implicated in neuroglial activation and functional maturation. The DNA microarray
      analyzed, 8913 probes. Sixty nine genes were up-regulated and 11 genes were down
      regulated at least twofold compared to normal control. Of the 80 genes, 23 were
      related to cell metabolism, 3 related to apoptosis, 27 related to immunity. Among
      them, 4 genes (Galectin 3, Heat shock protein 27, Lipocalin 2, Tissue inhibitory
      metalloproteinase 1) seemed to be related to the neuroglial function. The
      candidate genes were subjected to quantitative real-time PCR, Western blotting,
      and immunohistochemical approaches. Expression changes similar to the microarray
      were evident. In a double immunofluorescence assay, Galectin 3 almost completely
      co-localized with OX6-positive activated microglia, and Heat shock protein 27
      mainly co-localized with glial fibrillary acidic protein (GFAP) positive
      astrocytes. Lipocalin 2, except for a few matches of GFAP positive astrocytes,
      did not co-localized with any of neuroglial markers. This is the first study to
      evaluate gene expression changes in the SN following MFB transection, which has
      been used as a parkinsonian animal model. Several candidate genes with potential
      roles in neuroglial activation and functional maturation were identified. The
      molecular significance of the candidate genes in neuroglial activation and
      neuroinflammation remains unclear. 

PMID- 25858853
TI  - Leucine amplifies the effects of metformin on insulin sensitivity and glycemic
      control in diet-induced obese mice.
AB  - BACKGROUND AND OBJECTIVE: The Sirt1/AMPK signaling pathway is a key sensor of
      energy status and regulates glucose and lipid metabolism. Leucine (Leu) activates
      Sirt1 by lowering its Km for NAD(+) and potentiates other sirtuin/AMPK
      activators, resulting in improvement of insulin sensitivity. Since metformin
      (Met) converges on this pathway, we hypothesized that leucine would amplify its
      gluco-regulatory effects. MATERIALS AND METHODS: The effects of Leu (24 g/kg
      diet)+Met (0.05-0.5 g/kg diet) combinations were compared to standard therapeutic
      Met (1.5 g/kg diet; ~300 mg/kg BW) on glycemic control in high fat diet induced
      insulin resistant mice for 6 weeks. The effects of Leu on Met stimulation of
      Sirt1 and AMPK activities were further evaluated in adipocytes. RESULTS: Sub
      therapeutic levels of Met combined with Leu resulted in increases in Sirt1
      activity and in tissue P-AMPK/AMPK ratio and corresponding dose-responsive
      improvements in fasting and post-prandial glucose, in glucose response to an
      insulin tolerance test and in the area under the curve in glucose tolerance
      tests. Changes were evident within 7 days of treatment and sustained throughout
      the 6-week study duration. The Leu+Met (0.25 g/kg)-combinations produced a
      comparable effect to a standard therapeutic Met dose, while the Leu+Met (0.5 g/kg
      diet) resulted in greater improvements. Since resveratrol also synergizes with
      leucine to augment sirtuin signaling and insulin sensitivity, we tested the
      addition of resveratrol to Leu-Met and found no additional benefit. CONCLUSION:
      These data demonstrate that adding Leu to Met enables a dose reduction of 66%
      with improved efficacy and of 83% with comparable efficacy to standard metformin
      in diet-induced obese mice, and addition of resveratrol does not provide further
      benefit.

PMID- 25858854
TI  - Multifunctional liposomes constituting microneedles induced robust systemic and
      mucosal immunoresponses against the loaded antigens via oral mucosal vaccination.
AB  - To develop effective, convenient and stable mucosal vaccines, mannose-PEG
      cholesterol (MPC)/lipid A-liposomes (MLLs) entrapping model antigen bovine serum
      albumin (BSA) were prepared by the procedure of emulsification-lyophilization and
      used to constitute microneedles, forming the proMLL-filled microneedle arrays
      (proMMAs). The proMMAs were rather stable and hard enough to pierce porcine skin
      and, upon rehydration, dissolved rapidly recovering the MLLs without size and
      entrapment change. The proMMAs given to mice via oral mucosal (o.m.) route,
      rather than routine intradermal administration, elicited robust systemic and
      mucosal immunoresponses against the loaded antigens as evidenced by high levels
      of BSA-specific IgG in the sera and IgA in the salivary, intestinal and vaginal
      secretions of mice. Enhanced levels of IgG2a and IFN-gamma in treated mice
      revealed that proMMAs induced a mixed Th1/Th2 immunoresponse. Moreover, a
      significant increase in CD8(+) T cells confirmed that strong cellular immunity
      had also been established by the immunization of the proMMAs. Thus, the proMMAs
      can be immunized via o.m. route to set up an effective multiple defense against
      pathogen invasion and may be an effective vaccine adjuvant-delivery system (VADS)
      applicable in the controlled temperature chain. 

PMID- 25858855
TI  - Hepatitis B surface antigen (HBsAg) and core antigen (HBcAg) combine CpG
      oligodeoxynucletides as a novel therapeutic vaccine for chronic hepatitis B
      infection.
AB  - Hepatitis B virus infection is a non-cytopathic hepatotropic virus which can lead
      to chronic liver disease and hepatocellular carcinoma. Traditional therapies fail
      to provide sustained control of viral replication and liver damage in most
      patients. As an alternative strategy, immunotherapeutic approaches have shown
      promising efficacy in the treatment of chronic hepatitis B patients. Here, we
      investigated the efficacy of a novel therapeutic vaccine formulation consisting
      of two HBV antigens, HBsAg and HBcAg, and CpG adjuvant. This vaccine formulation
      elicits forceful humoral responses directed against HBsAg/HBcAg, and promotes a
      Th1/Th2 balance response against HBsAg and a Th1-biased response against HBcAg in
      both C57BL/6 and HBV transgenic mice. Vigorous cellular immune response was also
      detected in HBV transgenic mice, for a significantly higher number of HBs/HBc
      specific IFN-gamma secreting CD4+ and CD8+ T cells was generated. Moreover,
      vaccinated mice elicited significantly intense in vivo CTL attack, reduced serum
      HBsAg level without causing liver damage in HBV transgenic mice. In summary, this
      study demonstrates a novel therapeutic vaccine with the potential to elicit
      vigorous humoral and cellular response, overcoming tolerance in HBV transgenic
      mice. 

PMID- 25858856
TI  - Molecular signatures for vaccine development.
AB  - The immune system has evolved complex and specialized mechanisms to mount
      specific defense responses against the various types of pathogens it encounters.
      For the development of new vaccines, it is crucial to gain a better understanding
      of what these mechanisms are and how they work. The field of vaccinology has
      adopted high-throughput profiling techniques to gain more detailed insights into
      the various immune responses elicited by different vaccines and natural
      infections. From all detailed transcriptional profiles generated today, a general
      picture of immunological responses emerges. First, almost every type of vaccine
      induces an early interferon-dominated signature. Second, different vaccine
      formulations induce distinct transcriptional signatures, representing the highly
      specialized defense mechanisms that must cope with the different pathogens and
      insults they cause. Transcriptional profiling has shifted its attention toward
      early molecular signatures, with a growing awareness that early innate responses
      are likely critical instructors for the development of adaptive immunity at later
      time points. 

PMID- 25858857
TI  - Use of recombinant flagellin in oil-in-water emulsions enhances hemagglutinin
      specific mucosal IgA production and IL-17 secreting T cells against H5N1 avian
      influenza virus infection.
AB  - Researchers are currently involved in a strong effort to find a safe and
      effective vaccine against highly pathogenic avian influenza H5N1 viruses. Toward
      that goal, we obtained soluble recombinant flagellin (FliC) of Salmonella
      typhimurium to be used as a mucosal adjuvant for H5HA subunit vaccine
      development. Intranasal immunization of H5HA antigen with recombinant FliC
      protein in an oil-in-water emulsion increased H5HA-specific IgG and IgA titers in
      sera, bronchoalveolar lavage fluids (BALFs), and nasal washes. Use of FliC
      adjuvant for intranasal immunization further augmented B-cell responses in
      mucosal environments via increased IgA titers in BALFs and nasal washes.
      Increases in IgA and IgG titers through the use of FliC adjuvant in intranasal
      immunization correlated with higher neutralizing antibody titers in sera and
      BALFs and higher numbers of IgG- and IgA-secreting B cells in spleen and cervical
      lymph nodes. High levels of IL-17A cytokine production were also found in
      stimulated T cells of spleen and cervical lymph node cells, only by intranasal
      immunization particularly with the use of FliC adjuvant in oil-in-water
      emulsions. These findings may provide useful information toward the development
      of H5HA mucosal influenza vaccines. 

PMID- 25858858
TI  - sIPV process development for costs reduction.
AB  - Polio is expected to be eradicated within only a few years from now. Upon polio
      eradication, the use of oral polio vaccines, which can cause circulating and
      virulent vaccine derived polio viruses, will be stopped. From this moment
      onwards, inactivated polio vaccines (IPV) will be used for worldwide vaccination
      against polio. An increased demand for IPV is thus anticipated. As a result,
      process development studies regarding the IPV production process, developed in
      the 1960s, have intensified. Studies on yield optimization aiming at costs
      reduction as well as the use of alternative polio viruses, which are more biosafe
      for manufacturing, are actual. Here our strategy to setup a new IPV production
      process using attenuated Sabin polio virus strains is presented. Moreover,
      aspects on reduction of the costs of goods and the impact of process optimization
      on sIPV costs are reviewed. 

PMID- 25858859
TI  - An experimental subunit vaccine based on Bluetongue virus 4 VP2 protein fused to
      an antigen-presenting cells single chain antibody elicits cellular and humoral
      immune responses in cattle, guinea pigs and IFNAR(-/-) mice.
AB  - Bluetongue virus (BTV), the causative agent of bluetongue disease (BT) in
      domestic and wild ruminants, is worldwide distributed. A total of 27 serotypes
      have been described so far, and several outbreaks have been reported. Vaccination
      is critical for controlling the spread of BTV. In the last years, subunit
      vaccines, viral vector vaccines and reverse genetic-based vaccines have emerged
      as new alternatives to conventional ones. In this study, we developed an
      experimental subunit vaccine against BTV4, with the benefit of targeting the
      recombinant protein to antigen-presenting cells. The VP2 protein from an
      Argentine BTV4 isolate was expressed alone or fused to the antigen presenting
      cell homing (APCH) molecule, in the baculovirus insect cell expression system.
      The immunogenicity of both proteins was evaluated in guinea pigs and cattle.
      Titers of specific neutralizing antibodies in guinea pigs and cattle immunized
      with VP2 or APCH-VP2 were high and similar to those induced by a conventional
      inactivated vaccine. The immunogenicity of recombinant proteins was further
      studied in the IFNAR(-/-) mouse model where the fusion of VP2 to APCH enhanced
      the cellular immune response and the neutralizing activity induced by VP2. 

PMID- 25858861
TI  - Tribulus terrestris (Linn.) Attenuates Cellular Alterations Induced by Ischemia
      in H9c2 Cells Via Antioxidant Potential.
AB  - Tribulus terrestris L. was evaluated for its cardioprotective property against
      myocardial ischemia in a cell line model. Initially, methanolic extract was
      prepared and subjected to sequential extraction with various solvents. The
      extract with high phenolic content (T. terrestris L. ethyl acetate extract-TTME)
      was further characterized for its chemical constituents and taken forward for
      evaluation against cardiac ischemia. HPLC analysis revealed the presence of
      phenolic compounds like caffeic acid (12.41 +/- 0.22 mg g(-1)), chlorogenic acid
      (0.52 +/- 0.06 mg g(-1)) and 4-hydroxybenzoic acid (0.60 +/- 0.08 mg g(-1)). H9c2
      cells were pretreated with TTME (10, 25, 50 and 100 ug/ml) for 24 h before the
      induction of ischemia. Then ischemia was induced by exposing cells to ischemia
      buffer, in a hypoxic chamber, maintained at 0.1% O2, 95% N2 and 5% CO2, for 1 h.
      A significant (p <= 0.05) increase in reactive oxygen species generation (56%),
      superoxide production (18%), loss of plasma membrane integrity, dissipation of
      transmembrane potential, permeability transition pore opening and apoptosis had
      been observed during ischemia. However, pretreatment with TTME was found to
      significantly (p <= 0.05) attenuate the alterations caused by ischemia. The
      overall results of this study partially reveal the scientific basis of the use of
      T. terrestris L. in the traditional system of medicine for heart diseases.

PMID- 25858860
TI  - Systems vaccinology: Enabling rational vaccine design with systems biological
      approaches.
AB  - Vaccines have drastically reduced the mortality and morbidity of many diseases.
      However, vaccines have historically been developed empirically, and recent
      development of vaccines against current pandemics such as HIV and malaria has
      been met with difficulty. The advent of high-throughput technologies, coupled
      with systems biological methods of data analysis, has enabled researchers to
      interrogate the entire complement of a variety of molecular components within
      cells, and characterize the myriad interactions among them in order to model and
      understand the behavior of the system as a whole. In the context of vaccinology,
      these tools permit exploration of the molecular mechanisms by which vaccines
      induce protective immune responses. Here we review the recent advances,
      challenges, and potential of systems biological approaches in vaccinology. If the
      challenges facing this developing field can be overcome, systems vaccinology
      promises to empower the identification of early predictive signatures of vaccine
      response, as well as novel and robust correlates of protection from infection.
      Such discoveries, along with the improved understanding of immune responses to
      vaccination they impart, will play an instrumental role in development of the
      next generation of rationally designed vaccines. 

PMID- 25858862
TI  - 3D immersive patient simulators and their impact on learning success: a thematic
      review.
AB  - BACKGROUND: Immersive patient simulators (IPSs) combine the simulation of virtual
      patients with a three-dimensional (3D) environment and, thus, allow an
      illusionary immersion into a synthetic world, similar to computer games. Playful
      learning in a 3D environment is motivating and allows repetitive training and
      internalization of medical workflows (ie, procedural knowledge) without
      compromising real patients. The impact of this innovative educational concept on
      learning success requires review of feasibility and validity. OBJECTIVE: It was
      the aim of this paper to conduct a survey of all immersive patient simulators
      currently available. In addition, we address the question of whether the use of
      these simulators has an impact on knowledge gain by summarizing the existing
      validation studies. METHODS: A systematic literature search via PubMed was
      performed using predefined inclusion criteria (ie, virtual worlds, focus on
      education of medical students, validation testing) to identify all available
      simulators. Validation testing was defined as the primary end point. RESULTS:
      There are currently 13 immersive patient simulators available. Of these, 9 are
      Web-based simulators and represent feasibility studies. None of these simulators
      are used routinely for student education. The workstation-based simulators are
      commercially driven and show a higher quality in terms of graphical quality
      and/or data content. Out of the studies, 1 showed a positive correlation between
      simulated content and real content (ie, content validity). There was a positive
      correlation between the outcome of simulator training and alternative training
      methods (ie, concordance validity), and a positive coherence between measured
      outcome and future professional attitude and performance (ie, predictive
      validity). CONCLUSIONS: IPSs can promote learning and consolidation of procedural
      knowledge. The use of immersive patient simulators is still marginal, and
      technical and educational approaches are heterogeneous. Academic-driven IPSs
      could possibly enhance the content quality, improve the validity level, and make
      this educational concept accessible to all medical students.

PMID- 25858863
TI  - Distribution of lymphocyte subpopulations in patients with polycythemia vera.
AB  - Polycythemia vera (PV) is a disease with slow development. Nonetheless, the
      immune response is unable to eliminate the uncontrolled proliferating
      hematopoietic cells, leading to treatment of patient by phlebotomy and/or
      cytotoxic drugs. In addition, a higher incidence of cancers is observed in PV
      patients, independently of treatment. These observations argue for an impaired
      immune response in PV. In order to investigate this hypothesis, we studied the
      distribution of lymphocyte subpopulations in PV, and showed a significant
      decrease in T, TCR gamma/delta and B cells together with an increase in natural
      killer (NK) cells. 

PMID- 25858864
TI  - Evidence of association of interleukin-23 receptor gene polymorphisms with
      Egyptian rheumatoid arthritis patients.
AB  - BACKGROUND: The identification of additional genetic risk factor is an on-going
      process that will aid in the understanding of rheumatoid arthritis (RA)
      aetiology. A genome-wide association scan in Crohn's (CD) disease highlighted the
      interleukin-23 receptor (IL23R) gene as a susceptibility factor. Since the IL
      23/IL-17 pathway is known to associate with other autoimmune disease, including
      rheumatoid arthritis and systemic sclerosis, we hypothesised that IL23R could be
      a shared susceptibility gene. The rare allele of IL23R single nucleotide
      polymorphism (SNP) rs11209026 (Arg381Gln) confers strong protection against CD.
      Our aim was to analyse IL23R SNP (rs11209026, rs2201841, and rs10889677) and to
      detect its association with RA in Egyptian patients. METHODS: A group of Egyptian
      patients with RA (n=120) and apparently healthy persons as controls (n=120) was
      genotyped for rs11209026, rs2201841 and rs10889677 by real time/polymerase chain
      reaction (real-time/PCR) for the first SNP and restriction fragment length
      polymorphism/PCR (RFLP/PCR) in the last two SNPs. RESULTS: Our data emphasise
      that the AA genotype of rs11209026 (Arg381Gln) was significantly associated with
      RA patients compared to the controls (P value=0.001).We did not find any
      significant association between either rs2201841 or rs10889677 and the
      development of rheumatoid arthritis (P value=1.000 & 0.562 respectively).
      CONCLUSION: Our results suggest that IL23 receptor AA genotype variant of
      rs11209026 would contribute to RA aetiology; consequently, it might be a genetic
      marker for RA. We need to address the subgroup of patients who will benefit from
      the selective suppression of the IL23 signalling which would represent new
      perspectives toward a personalized therapy of RA patients by further studies.

PMID- 25858865
TI  - Gold nanoparticles with different charge and moiety induce differential cell
      response on mesenchymal stem cell osteogenesis.
AB  - Stem cells exist in an in vivo microenvironment that provides biological and
      physiochemical cues to direct cell fate decisions. How the stem cells sense and
      respond to these cues is still not clearly understood. Gold nanoparticles (AuNPs)
      have been widely used for manipulation of cell behavior due to their ease of
      synthesis and versatility in surface functionalization. In this study, AuNPs with
      amine (AuNP-NH2), carboxyl (AuNP-COOH) and hydroxyl (AuNP-OH) functional groups
      possessing different surface charge were synthesized. Human bone marrow-derived
      mesenchymal stem cells (hMSCs) were treated with the surface functionalized AuNPs
      and assessed for cell viability and osteogenic differentiation ability. The
      surface functionalized AuNPs were well tolerated by hMSCs and showed no acute
      toxicity. Positively charged AuNPs showed higher cellular uptake. AuNPs did not
      inhibit osteogenesis but ALP activity and calcium deposition were markedly
      reduced in AuNP-COOH treatment. Gene profiling revealed an upregulation of TGF
      beta and FGF-2 expression that promoted cell proliferation over osteogenic
      differentiation in hMSCs. These results provide some insight on the influence of
      surface functionalized AuNPs on hMSCs behavior and the use of these materials for
      strategic tissue engineering. 

PMID- 25858866
TI  - Exposure medium: key in identifying free Ag+ as the exclusive species of silver
      nanoparticles with acute toxicity to Daphnia magna.
AB  - It is still not very clear what roles the various Ag species play in the toxicity
      of silver nanoparticles (AgNPs). In this study, we found that traditional
      exposure media result in uncontrollable but consistent physicochemical
      transformation of AgNPs, causing artifacts in determination of median lethal
      concentration (LC50) and hindering the identification of Ag species responsible
      for the acute toxicity of AgNPs to Daphnia magna. This obstacle was overcome by
      using 8 h exposure in 0.1 mmol L(-1) NaNO3 medium, in which we measured the 8-h
      LC50 of seven AgNPs with different sizes and coatings, and determined the
      concentrations of various Ag species. The LC50 as free Ag(+) of the seven AgNPs
      (0.37-0.44 MUg L(-1)) agreed very well with that of AgNO3 (0.40 MUg L(-1)), and
      showed the lowest value compared to that as total Ag, total Ag(+), and dissolved
      Ag, demonstrating free Ag(+) is exclusively responsible for the acute toxicity of
      AgNPs to D. magna, while other Ag species in AgNPs have no contribution to the
      acute toxicity. Our results demonstrated the great importance of developing
      appropriate exposure media for evaluating risk of nanomaterials. 

PMID- 25858867
TI  - Overview of biomarkers for diagnosis and monitoring of celiac disease.
AB  - Among the adverse reactions caused by wheat, celiac disease (CD) is the longest
      studied and best-known pathology. The more recently defined non-celiac gluten
      sensitivity (NCGS) presents with symptoms which are often indistinguishable from
      CD. Diagnosis of CD is based on serologic, molecular, and bioptic testing. The
      IgA anti-transglutaminase (tTG) test is considered highly important, as it shows
      high sensitivity and specificity and its levels correlate to the degree of
      intestinal damage. Small bowel biopsy can be avoided in symptomatic patients with
      IgA anti-tTG levels above 10* the manufacturer's cut-off. Recently, tests of anti
      deamidated peptides of gliadin (DGP) have replaced classic anti-native gliadin
      (AGA) tests. DGP assays have a considerably higher diagnostic accuracy than AGA
      assays, especially in the IgG class, and can replace anti-tTG tests in patients
      with selective IgA deficiency. The combination of IgG anti-DGP plus IgA anti-tTG
      assays show greater sensitivity than a single test, with very high specificity.
      EMA tests have great diagnostic accuracy but are not recommended by all the
      latest guidelines because they are observer dependent. Biopsy must still be
      considered the gold standard for CD diagnosis. HLA-DQ genotyping can be used to
      screen asymptomatic children and in cases of histology/serology disagreement.
      About half of NCGS patients are DQ2 positive and have IgG AGA. To diagnose NCGS,
      first CD and wheat allergy must be excluded; then the wheat dependence of
      symptoms must be verified by a gluten-free diet and subsequent gluten challenge. 

PMID- 25858868
TI  - Cystatin C: a kidney function biomarker.
AB  - Renal function is essential for homeostasis. The kidneys play important
      pleiotropic roles including removal of metabolic waste products and maintenance
      of water-electrolyte balance and blood pressure. Early diagnosis of renal
      dysfunction and institution of appropriate therapy are vital to survival.
      Unfortunately, common indicators of renal function lack necessary sensitivity and
      specificity. Recent evidence has, however, suggested that cystatin C (cysC) may
      be useful as a marker for glomerular filtration. CysC is a protein belonging to a
      group of cysteine proteases inhibitors produced primarily by nucleated cells. Due
      to low molecular weight and positive pI, it is easily filtered. Moreover, its
      serum concentration is independent of gender, age, or muscle mass, i.e., typical
      confounders in assessing glomerular filtration rate (GFR). This chapter discusses
      the structure and biologic function of cysC, its role as an indicator of GFR, and
      the most frequently used methods for its determination. 

PMID- 25858869
TI  - Procalcitonin: potential role in diagnosis and management of sepsis.
AB  - Sepsis is an important cause of worldwide morbidity and mortality. Early
      recognition and diagnosis are keys to achieving improved outcomes. Procalcitonin
      has been widely investigated as a potential biomarker for sepsis. Furthermore,
      management of sepsis and other infectious disease is becoming increasingly
      complicated by the emergence of antibiotic resistant strains of pathogens. Good
      antibiotic governance is important in reducing the risk of the development of
      further antibiotic resistance. We reviewed the current literature on the use of
      procalcitonin in sepsis to determine whether it should be recommended for use in
      either of these roles. Procalcitonin should not be used as a stand-alone
      diagnostic test to rule-in or rule-out sepsis or bacterial infection, or for
      prognostication, in the absence of clinical judgment. Used as part of a clinical
      algorithm, however, it has been shown to reduce antibiotic prescribing in
      critical care environments and for respiratory tract infections. 

PMID- 25858870
TI  - Manganese superoxide dismutase and oxidative stress modulation.
AB  - Oxidative stress is characterized by imbalanced reactive oxygen species (ROS)
      production and antioxidant defenses. Two main antioxidant systems exist. The
      nonenzymatic system relies on molecules to directly quench ROS and the enzymatic
      system is composed of specific enzymes that detoxify ROS. Among the latter, the
      superoxide dismutase (SOD) family is important in oxidative stress modulation. Of
      these, manganese-dependent SOD (MnSOD) plays a major role due to its
      mitochondrial location, i.e., the main site of superoxide (O(2)(.-)) production.
      As such, extensive research has focused on its capacity to modulate oxidative
      stress. Early data demonstrated the relevance of MnSOD as an O(2)(.-) scavenger.
      More recent research has, however, identified a prominent role for MnSOD in
      carcinogenesis. In addition, SOD downregulation appears associated with health
      risk in heart and brain. A single nucleotide polymorphism which alters the
      mitochondria signaling sequence for the cytosolic MnSOD form has been identified.
      Transport into the mitochondria was differentially affected by allelic presence
      and a new chapter in MnSOD research thus begun. As a result, an ever-increasing
      number of diseases appear associated with this allelic variation including
      metabolic and cardiovascular disease. Although diet and exercise upregulate
      MnSOD, the relationship between environmental and genetic factors remains
      unclear.

PMID- 25858871
TI  - Selenium and selenium-dependent antioxidants in chronic kidney disease.
AB  - Oxidative stress plays a key role in numerous disease processes including chronic
      kidney disease (CKD). In general, oxygen metabolism leads to the formation of
      reactive oxygen species (ROS) dangerous to cells. Although enzymes and low
      molecular-weight antioxidants protect against ROS, chronic imbalances of
      formation and elimination can eventually overwhelm endogenous defenses leading to
      deleterious consequences. In CKD, glutathione peroxidases (GSH-Px) play an
      important role in ROS metabolism. Plasma GSH-Px is synthesized in the kidney and
      requires selenium (Se) as a cofactor. Interestingly, Se and plasma GSH-Px are
      both significantly reduced in CKD, especially for those patients on hemodialysis.
      Supplementation of Se in these patients results in modest increases of GSH-Px,
      presumably from residual renal tissue. Kidney transplantation rapidly restores
      plasma GSH-Px. In this chapter, the relevance of these findings to CKD is
      explored with emphasis on renal disease processes and impact on attendant
      disorders including cancer and cardiovascular disease. 

PMID- 25858872
TI  - Lipidomics: new insight into kidney disease.
AB  - Due to the incidence of type-2 diabetes and hypertension, chronic kidney disease
      (CKD) has emerged as a major public health problem worldwide. CKD results in
      premature death from accelerated cardiovascular disease and various other
      complications. Early detection, careful monitoring of renal function, and
      response to therapeutic intervention are critical for prevention of CKD
      progression and its complications. Unfortunately, traditional biomarkers of renal
      function are insufficiently sensitive or specific to detect early stages of
      disease when therapeutic intervention is most effective. Therefore, more
      sensitive biomarkers of kidney disease are needed for early diagnosis,
      monitoring, and effective treatment. CKD results in profound changes in lipid and
      lipoprotein metabolism that, in turn, contribute to progression of CKD and its
      cardiovascular complications. Lipids and lipid-derived metabolites play diverse
      and critically important roles in the structure and function of cells, tissues,
      and biofluids. Lipidomics is a branch of metabolomics, which encompasses the
      global study of lipids and their biologic function in health and disease
      including identification of biomarkers for diagnosis, prognosis, prevention, and
      therapeutic response for various diseases. This review summarizes recent
      developments in lipidomics and its application to various kidney diseases
      including chronic glomerulonephritis, IgA nephropathy, chronic renal failure,
      renal cell carcinoma, diabetic nephropathy, and acute renal failure in clinical
      and experimental research. Analytical technologies, data analysis, as well as
      currently known metabolic biomarkers of kidney diseases are addressed. Future
      perspectives and potential limitations of lipidomics are discussed. 

PMID- 25858873
TI  - Advances in biomarkers of major depressive disorder.
AB  - Major depressive disorder (MDD) is characterized by mood, vegetative, cognitive,
      and even psychotic symptoms and signs that can cause substantial impairments in
      quality of life and functioning. Biomarkers are measurable indicators that could
      help diagnosing MDD or predicting treatment response. In this chapter, lipid
      profiles, immune/inflammation, and neurotrophic factor pathways that have long
      been implicated in the pathogenesis of MDD are discussed. Then, pharmacogenetics
      and epigenetics of serotonin transport and its metabolism pathway, brain-derived
      neurotrophic factor, and abnormality of hypothalamo-pituitary-adrenocortical axis
      also revealed new biomarkers. Lastly, new techniques, such as proteomics and
      metabolomics, which allow researchers to approach the studying of MDD with new
      directions and make new discoveries are addressed. In the future, more data are
      needed regarding pathophysiology of MDD, including protein levels, single
      nucleotide polymorphism, epigenetic regulation, and clinical data in order to
      better identify reliable and consistent biomarkers for diagnosis, treatment
      choice, and outcome prediction. 

PMID- 25858874
TI  - The first volume of the Advances in Clinical Chemistry series for 2015 is
      presented. Introduction.

PMID- 25858875
TI  - Celastrol ameliorates experimental colitis in IL-10 deficient mice via the up
      regulation of autophagy.
AB  - BACKGROUND: Celastrol had been proved effective in the treatment for IBD,
      probably with the modulation of oxidative stress, inflammatory cytokines and
      intestinal homeostasis. This study was aimed to investigate whether celastrol
      could ameliorate the inflammation of IL-10 deficient mice, a murine model of
      Crohn's disease (CD) with the induction of autophagy. MATERIAL AND METHODS: The
      mice included were divided into four groups, ##WT group, IL-10(-/-) group, Cel
      group and Control group (celastrol+3-Methyladenine). Celastrol (2 mg/kg)
      treatment by gavage was administered to mice daily over one week. 3-Methyladenine
      (autophagy inhibitors) was administered at a dose of 30 mg/kg by intraperitoneal
      injection. The histological evaluation of the colon, tissue myeloperoxidase
      (MPO), and colon inflammation of mice in the four groups was evaluated and
      compared. Furthermore, the PI3K/Akt/mTOR pathway and the status of autophagy in
      intestine affected by celastrol were also assessed. RESULTS: The one-week
      administration of celastrol ameliorated established colitis in IL-10 deficient
      mice, associated with a reduction of marked histological inflammation, a
      decreased colon MPO concentration and suppression of colonic proinflammatory
      cytokine. Furthermore, the decreased neutrophil infiltration in proximal colon
      and improvement of inflammation in the Cel group was much more obvious than that
      in the Control group. The Western blotting analysis of the PI3K/Akt/mTOR pathway
      and autophagy showed that celastrol treatment up-regulated the autophagy of colon
      tissue by suppressing the PI3K/Akt/mTOR signaling pathway. CONCLUSIONS: Celastrol
      ameliorates experimental colitis in IL-10 deficient mice via the up-regulation of
      autophagy by suppressing the PI3K/Akt/mTOR signaling pathway.

PMID- 25858877
TI  - Co-exposure to aluminum and acrylamide disturbs expression of metallothionein,
      proinflammatory cytokines and induces genotoxicity: Biochemical and
      histopathological changes in the kidney of adult rats.
AB  - The individual toxic effects of aluminum and acrylamide are known but there is no
      data on their combined effects. The present study investigates the toxic effects
      after combined exposure to these toxicants on: (i) oxidative stress during
      combined chronic exposure to aluminum and acrylamide on kidney function (ii)
      correlation of oxidative stress with metallothionein (MT) and inflammatory
      cytokines expression, DNA damage, and histopathological changes. Rats were
      exposed to aluminum (50 mg/kg body weight) in drinking water and acrylamide (20
      mg/kg body weight) by gavage either individually or in combination for 3 weeks.
      Exposure rats to aluminum chloride or acrylamide alone and in combination induced
      nephrotoxicity, as evidenced by a decrease in the 24-h urine volume and uric acid
      levels in plasma and an increase of plasma creatinine, urea, and blood urea
      nitrogen levels. Nephrotoxicity was objectified by a significant increase in
      malondialdehyde level, advanced oxidation protein, and protein carbonyl contents,
      whereas reduced glutathione, nonprotein thiol, vitamin C levels, catalase, and
      glutathione peroxidase activities showed a significant decline. Superoxide
      dismutase activity and its gene expression were increased. Aluminum and
      acrylamide co-exposure exhibited synergism in various biochemical variables and
      also in DNA damage. Kidney total MT levels and genes expression of MT1, MT2, and
      proinflammatory cytokines were increased. All these changes were supported by
      histopathological observations. Co-exposure to aluminum and acrylamide exhibited
      synergism and more pronounced toxic effects compared with their individual
      effects based on various biochemical variables, genotoxic, and histopathological
      changes. (c) 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1044-1058, 2016. 

PMID- 25858876
TI  - Immunomodulatory activity of Melaleuca alternifolia concentrate (MAC): inhibition
      of LPS-induced NF-kappaB activation and cytokine production in myeloid cell
      lines.
AB  - Melaleuca alternifolia concentrate (MAC) is a mixture predominantly composed of
      monoterpenoids and sesquiterpenes, refined from the essential oil of the tea tree
      by removing up to 99% of the more toxic, hydrophobic monoterpenes. MAC was
      examined here for its immunomodulatory effects on the human THP1 and murine
      RAW264.7 myeloid leukemic cell lines as models for macrophage-like cells.
      Firstly, MAC levels were determined that did not affect either the survival or
      proliferation of these cell lines in vitro. Next, the levels of
      lipopolysaccharide (LPS)-induced production of cytokines (IL-6, TNFalpha, IL-10,
      GM-CSF, IFNgamma and IL-3) were examined from the myeloid cell lines using
      multiplex assays. Many of the LPS-inducible cytokines produced by either cell
      lines could be significantly inhibited by MAC. Closer examination of the
      mechanism of action of MAC showed that it inhibited the LPS-induced activation of
      IkappaB phosphorylation and nuclear factor (NF)-kappaB signalling and
      translocation, inhibiting iNOS protein expression and NO production. These
      results demonstrate that MAC exerts its immunomodulatory effects by inhibiting NF
      kappaB signalling activation and levels of cytokine production by macrophage-like
      cell lines.

PMID- 25858878
TI  - One-step synthesis of CDTA coated magnetic nanoparticles for selective removal of
      Cu(II) from aqueous solution.
AB  - A novel 1,2-cyclohexylenedinitrilotetraacetic acid (CDTA) modified Fe3O4 magnetic
      nanoparticles (MNPs) was synthesized by one-step solvothermal method and used as
      solid phase extraction (SPE) material to preconcentrate trace copper coupled with
      flame atomic absorption spectrometry (FAAS). The synthesized adsorbents were
      characterized by field emission scanning electron microscopy and X-ray powder
      diffraction with a nanoscale. The optimum conditions for the absorption process
      were investigated on several commonly tested experimental parameters such as pH
      of the solution, ultrasound time, sample volume, concentration and volume of
      elution solution. The influences of some anions and cations on the recoveries of
      Cu(II) ions were also investigated, and no considerable interference was
      observed. The maximum adsorption capacity of Fe3O4 magnetic nanoparticles and
      CDTA modified Fe3O4 magnetic nanoparticles were found to be 27.50 mg/g and 78.24
      mg/g for Cu(II). The developed method was applied to the determination of Cu(II)
      in tap and lake water samples with recoveries ranging from 96.4% to 99.1%.

PMID- 25858879
TI  - Spectroscopic and molecular docking studies on the interaction of troxerutin with
      DNA.
AB  - Troxerutin (TXER) is a derivative of naturally occurring bioflavonoid rutin. It
      possesses different biological activities in rising clinical world. The
      biological activity possessed by most of the drugs mainly targets on
      macromolecules. Hence, in the current study we have examined the interaction
      mechanism of TXER with calf thymus DNA (CT-DNA) by using various spectroscopic
      methods, isothermal titration calorimetry (ITC) and molecular docking studies.
      Further, DNA cleavage study was carried out to find the DNA protection activity
      of TXER. UV-absorption and emission spectroscopy showed low binding constant
      values via groove binding. Circular dichroism study indicates that TXER does not
      modify native B-form of DNA, and it retains the native B-conformation.
      Furthermore, no effective positive potential peak shift was observed in TXER-DNA
      complex during electrochemical analysis by which it represents an interaction of
      TXER with DNA through groove binding. Molecular docking study showed thymine
      guanine based interaction with docking score -7.09 kcal/mol. This result was
      compared to experimental ITC value. The DNA cleavage study illustrates that TXER
      does not cause any DNA damage as well as TXER showed DNA protection against
      hydroxyl radical induced DNA damage. From this study, we conclude that TXER
      interacts with DNA by fashion of groove binding.

PMID- 25858880
TI  - Oral delivery of nanoparticles containing anticancer SN38 and hSET1 antisense for
      dual therapy of colon cancer.
AB  - An oral delivery system intended for treatment of colon cancer in HT29 cancerous
      cells was investigated by encapsulating hSET1 antisense and SN38 anticancer in
      nanoparticles based on cysteine trimethyl chitosan (cysTMC) and carboxymethyl
      dextran (CMD). Studies have shown hSET1 as the main type of histone
      methyltransferase (HMT) complex, is significantly overexpressed in malignant
      cells. In this study, hSET1 antisense was employed to inhibit gene expression.
      Additionally, SN38 was incorporated into nanoparticles to enhance the efficiency
      of the system by inhibition of topoisomerase 1. CysTMC was synthetized and
      characterized by (1)H NMR and FTIR. Nanoparticles were prepared through
      complexation of CMD and cysTMC. Particle size and surface charge was 100-150 nm
      and 17-21 mV respectively with drug content of around 2.6%. Gel electrophoresis
      assay proved the stability of antisense in simulated gastric and intestinal
      fluids. Nanoparticles showed high mucoadhesion and glutathione responsive
      release. Cellular uptake was observed by confocal microscopy and quantified by
      flow cytometry. Cytotoxicity of NPs was assessed using MTT assay. Results showed
      hSET1/SN38 nanoparticles had significantly higher cytotoxicity against HT29 cells
      compared with nanoparticles containing SN38, free SN38 or naked hSET1. Therefore,
      present system could be considered an effective combination therapy of highly
      hydrophobic SN38 and hSET1.

PMID- 25858881
TI  - Maternal low-protein diet causes body weight loss in male, neonate Sprague-Dawley
      rats involving UCP-1-mediated thermogenesis.
AB  - Brown adipose tissue (BAT) plays an important role in regulating body weight (BW)
      by modifying thermogenesis. Maternal low protein (LP) diets reduce offspring
      birth weight. Increased BAT thermogenesis in utero may be one mechanism for the
      lower BW. However, whether maternal LP nutrition alters BAT thermogenesis and BW
      of offspring in utero is not yet known. We fed obese-prone Sprague-Dawley dams 8%
      LP or 20% normal protein (NP) diets for 3 weeks prior to breeding and through
      pregnancy. BW and gene expression of interscapular BAT (iBAT) thermogenic markers
      were measured in male fetal (gestation day 18) and neonatal (day 0 or 1)
      offspring. BW of neonatal LP males was lower than NP males but no difference was
      observed in females. Gene and protein expression of UCP-1 and transcription
      factors PRDM16 and PPARalpha in iBAT were 2- to 6-fold greater in LP than in NP
      male neonatal offspring. FNDC5, a precursor of irisin and activator of
      thermogenesis, was expressed 2-fold greater in neonatal LP iBAT than NP males.
      However, fetal iBAT UCP-1, PRDM16, PPARalpha and irisin mRNA did not differ
      between LP and NP groups. Maternal LP diet had no effects on placental irisin and
      UCP-2 expression. These results suggest that prenatal protein restriction
      increases the risk for low BW through mechanisms affecting full-term offspring
      iBAT thermogenesis but not greatly altering fetal iBAT or placental
      thermogenesis.

PMID- 25858882
TI  - Characterization of Circulating Tumor DNA for Genetic Assessment of solid Tumors.
AB  - Personalized cancer therapy requires characterization of the current status of an
      individual's cancer, necessitating invasive tumor tissue biopsies at diagnosis,
      during treatment and at progression. Serial acquisition of solid tumor biopsies
      during treatment to characterize mutations related to acquired resistance may not
      be medically feasible. Circulating tumor DNA (ctDNA) in plasma offers a possible
      noninvasive "real time" tool for tumor characterization, providing accessible
      genetic biomarkers for cancer diagnosis, prognosis, and response to therapy. 

PMID- 25858883
TI  - Met Expectations and Satisfaction with Duration: A Patient-Centered Evaluation of
      Breastfeeding Outcomes in the Infant Feeding Practices Study II.
AB  - BACKGROUND: Breastfeeding expectations predict breastfeeding duration. The extent
      to which expectations for duration are met remains unknown. OBJECTIVES: To
      evaluate prospective measures of expected breastfeeding duration, changes in
      expectations over time, and factors associated with meeting expectations.
      METHODS: The Infant Feeding Practices Study II followed women from late pregnancy
      to 1 year postpartum. Expected breastfeeding duration was assessed 5 times.
      Logistic regression identified factors associated with met prenatal expectations.
      Subgroup analysis compared met prenatal expectations to satisfaction with
      breastfeeding duration. RESULTS: One-year postpartum, 34.7% of 1802 participants
      had met prenatal expected breastfeeding duration, and 23.9% were still
      breastfeeding. Fifty-eight percent of women met expectations stated at 7 months
      postpartum. Modifiable risk factors associated with meeting prenatal expectations
      included early regular breast pump use (odds ratio [OR], 1.55; 95% confidence
      interval [CI], 1.18-2.07). Return to work was negatively associated with met
      expectations (return by 6 weeks postpartum: OR, 0.48; 95% CI, 0.33-0.71; later
      return: OR, 0.73; 95% CI, 0.56-0.95). Among those who reported on satisfaction
      with duration (n = 1226), 40.4% were satisfied. Satisfaction was associated with
      meeting expectations (OR, 10.56; 95% CI, 7.67-14.55), but expectation and
      satisfaction measures were not equivalent. Elevated body mass index and
      depressive symptoms at 2 months postpartum were negatively associated with both
      measures. CONCLUSION: Most participants did not meet prenatal or postnatal
      expectations for breastfeeding duration and were unsatisfied with duration.
      However, at 12 months, more participants felt they had met their expectations and
      were satisfied with their breastfeeding duration than were actually
      breastfeeding. Therefore, women may perceive greater breastfeeding progress than
      suggested by Healthy People 2020 benchmarks.

PMID- 25858884
TI  - Fish oil-based lipid emulsion: current updates on a promising novel therapy for
      the management of parenteral nutrition-associated liver disease.
AB  - Intestinal failure is characterized by loss of enteral function to absorb
      necessary nutrients and water to sustain life. Parenteral nutrition (PN) is a
      lifesaving therapeutic modality for patients with intestinal failure. Lifelong PN
      is also needed for patients who have short bowel syndrome due to extensive
      resection or a dysmotility disorder with malabsorption. However, prolonged PN is
      associated with short-term and long-term complications. Parenteral nutrition
      associated liver disease (PNALD) is one of the long-term complications associated
      with the use of an intravenous lipid emulsion to prevent essential fatty acid
      deficiency in these patients. PNALD affects 30-60% of the adult population on
      long-term PN. Further, PNALD is one of the indications for isolated liver or
      combined liver and intestinal transplantation. There is no consensus on how to
      manage PNALD, but fish oil-based lipid emulsion (FOBLE) has been suggested to
      play an important role both in its prevention and reversal. There is significant
      improvement in liver function in those who received FOBLE as lipid supplement
      compared with those who received soy-based lipid emulsion. Studies have also
      demonstrated that FOBLE reverses hepatic steatosis and reduces markers of
      inflammation in patients on long-term PN. Future prospective studies with larger
      sample sizes are needed to further strengthen the positive role of FOBLE in
      PNALD. 

PMID- 25858885
TI  - Could the grade of the tumour be related to nodal involvement?

PMID- 25858886
TI  - Reply to Cubuk and Yucel.

PMID- 25858887
TI  - Haplo graft engineering: sculpting to a T.
AB  - In this issue of Blood, Airoldi et al find that gammadelta T cells can provide
      critical antiviral and antileukemia effects after HLA-haploidentical
      hematopoietic transplants depleted of alphabeta T cells.

PMID- 25858888
TI  - Mutations in complement C3 from aHUS patients.
AB  - In this issue of Blood, Schramm et al demonstrate that the majority of mutations
      in complement C3 identified in atypical hemolytic uremic syndrome (aHUS) patients
      cause dysregulation in the alternative pathway of complement.

PMID- 25858889
TI  - Macro-quest.
AB  - In this issue of Blood, Paiva et al provide important information on the cell of
      origin in Waldenstrom macroglobulinemia (WM), a longstanding puzzle due to
      conflicting and incomplete data.

PMID- 25858890
TI  - Why "R" HIT patients predisposed to thrombosis?
AB  - In this issue of Blood, Rollin et al demonstrate that heparin-induced
      thrombocytopenia and thrombosis (HIT) patients homozygous for arginine (R) at
      position 131 in the immunoglobulin (Ig)G receptor FcgammaRIIA have a
      significantly higher incidence of thrombosis, and show that plasma IgG may play a
      key role in modulating the thrombotic process.

PMID- 25858891
TI  - The primacy of IL-6 in IPS?
AB  - In this issue of Blood, Varelias and colleagues demonstrate a central role of
      interleukin (IL)-6 in idiopathic pneumonia syndrome (IPS) after allogeneic stem
      cell transplantation (SCT) in both mice and humans.

PMID- 25858892
TI  - Regression of an HCV-associated disseminated marginal zone lymphoma under IFN
      free antiviral treatment.

PMID- 25858893
TI  - Common cancer-associated PIK3CA activating mutations rarely occur in Langerhans
      cell histiocytosis.

PMID- 25858894
TI  - Low frequency of mutations in Chinese with acute myeloid leukemia: Different
      disease or different aetiology?
AB  - Mutations in FLT3, DNMT3A, NRAS, NF1 and TP53 occur in persons of predominately
      European descent with acute myeloid leukemia (AML). Some, such as internal tandem
      duplication of FLT3 (FLT3-ITD) and point mutations in DNMT3A and NRAS, are
      especially frequent whereas others such as NF1 and TP53 are less so. Frequencies
      of these mutations in persons with seemingly similar AML from other genetic
      groups are largely unknown. We studied 269 Chinese (mostly Han) with de novo AML.
      FLT3-ITD was detected in 51 subjects (23%; 95% CI, 17-28%), R882 mutation of
      DNMT3A in 17 (6%; 95% CI, 3-9%) and NRAS mutation in 17 (7%; 95% CI, 3-9%). No
      mutations in NF1 and only 1 mutation in TP53 (1%, 95% CI, <2.5%) were detected.
      Except for FLT3-ITD, frequencies of these mutations are significantly less than
      those in persons of predominately European descent with AML. The reason(s) for
      this disparity is unknown but may offer clues to the aetiology of AML in
      different populations or may indicate some mutations associated with AML in
      persons of predominately European descent are not fundamental to the aetiology of
      the disease.

PMID- 25858895
TI  - Survival of patients with mixed phenotype acute leukemias: A large population
      based study.
AB  - Little is known about the incidence and treatment outcome of patients with acute
      biphenotypic leukemias. The World Health Organization (WHO) established the term
      of acute leukemia of ambiguous phenotype in 2001 (revised in 2008) introducing
      the term of mixed phenotype acute leukemias. Using the database of the
      Surveillance, Epidemiology, and End Results registry (SEER), we identified 313
      patients with mixed phenotype acute leukemias and compared them with 14,739
      patients with acute lymphoblastic leukemia and 34,326 patients with acute
      myelogenous leukemias diagnosed between 2001 and 2011. As a further control
      group, 1777 patients were included who were not classified as myeloid, lymphoid
      or biphenotypic (other acute leukemias). The incidence of mixed phenotype acute
      leukemias is 0.35 cases/1,000,000 person-years. In a multivariate analysis, the
      prognosis depends strongly on age (as with other leukemias) and it has the worst
      outcome of all four types of leukemia. However, the prognosis has improved,
      comparing 2001-2005 with 2006-2011. We present the first comprehensive,
      population-based study of acute biphenotypic or mixed phenotype acute leukemias
      according to the WHO classification. Especially in older patients, the prognosis
      is unfavorable and new treatments should be investigated. 

PMID- 25858896
TI  - Tactile Massage as Part of the Caring Act: A Qualitative Study in Short-Term
      Emergency Wards.
AB  - AIMS AND OBJECTIVES: The aim of this study was to illuminate the nursing staff's
      lived experiences and meaning in giving tactile massage (TM) while caring for
      patients in short-term emergency ward. METHOD: Data were collected through
      individual qualitative interviews with six nurses and eight assistant nurses
      working with TM in short-term emergency wards in two hospitals in Sweden. The
      narratives were analyzed using a phenomenological hermeneutical method. FINDINGS:
      Nurses experienced providing TM to patients as a present awareness in connection
      with compassion for the patient. TM provided the nurses with a tool to ease
      patient suffering and pain. Three dimensions were found where touch became a tool
      of doing, was an aware presence as a mindful being, and was embodied in a human
      to-human connection with a changed caregiver. CONCLUSION: Given the current high
      tech health care system with overcrowded units and a shortage of nursing staff,
      TM could be included as a caring tool to improve the caring in caregiving,
      allowing nurses to act in aware presence by touch to encourage health and well
      being for both the patient and themselves.

PMID- 25858897
TI  - Conceptualizing Telehealth in Nursing Practice: Advancing a Conceptual Model to
      Fill a Virtual Gap.
AB  - Increasingly nurses use various telehealth technologies to deliver health care
      services; however, there has been a lag in research and generation of empirical
      knowledge to support nursing practice in this expanding field. One challenge to
      generating knowledge is a gap in development of a comprehensive conceptual model
      or theoretical framework to illustrate relationships of concepts and phenomena
      inherent to adoption of a broad range of telehealth technologies to holistic
      nursing practice. A review of the literature revealed eight published conceptual
      models, theoretical frameworks, or similar entities applicable to nursing
      practice. Many of these models focus exclusively on use of telephones and four
      were generated from qualitative studies, but none comprehensively reflect
      complexities of bridging nursing process and elements of nursing practice into
      use of telehealth. The purpose of this article is to present a review of existing
      conceptual models and frameworks, discuss predominant themes and features of
      these models, and present a comprehensive conceptual model for telehealth nursing
      practice synthesized from this literature for consideration and further
      development. This conceptual model illustrates characteristics of, and
      relationships between, dimensions of telehealth practice to guide research and
      knowledge development in provision of holistic person-centered care delivery to
      individuals by nurses through telehealth technologies. 

PMID- 25858898
TI  - Hereditary systemic immunoglobulin light-chain amyloidosis.
AB  - Several members of a family died from renal failure as a result of systemic
      amyloidosis. Extensive studies to detect previously documented gene mutations
      associated with amyloidosis failed to identify a causative factor. In search of
      the genetic basis for this syndrome, amyloid fibrils were isolated from renal
      tissue of a member of the kin who died while on renal dialysis. Amino acid
      sequencing of isolated amyloid protein identified sequences compatible with the
      constant region of the immunoglobulin kappa light-chain. Isolation and
      characterization of kappa light-chain protein from serum of an affected member of
      the kindred revealed mutation in the constant region of kappa light-chain, with
      cysteine replacing serine at amino acid residue 131. This mutation (Ser131Cys)
      was confirmed by DNA analysis, which identified a single-base change of cytosine
      to guanine at the second position of codon 131 of the kappa light-chain gene
      (TCT131TGT). DNA analysis of members of the extended family revealed transmission
      of the Ser131Cys mutation and association with systemic amyloidosis. This amyloid
      light-chain (AL) amyloidosis, which is a hereditary type of amyloidosis and not
      the result of a monoclonal plasma cell dyscrasia, may be misdiagnosed and lead to
      inappropriate chemotherapy. 

PMID- 25858899
TI  - A Cost-Effectiveness Analysis of Community Health Workers in Mozambique.
AB  - INTRODUCTION: Community health worker (CHW) programs are a key strategy for
      reducing mortality and morbidity. Despite this, there is a gap in the literature
      on the cost and cost-effectiveness of CHW programs, especially in developing
      countries. METHODS: This study assessed the costs of a CHW program in Mozambique
      over the period 2010-2012. Incremental cost-effectiveness ratios, comparing the
      change in costs to the change in 3 output measures, as well as gains in
      efficiency were calculated over the periods 2010-2011 and 2010-2012. The results
      were reported both excluding and including salaries for CHWs. RESULTS: The
      results of the study showed total costs of the CHW program increased from US$1.34
      million in 2010 to US$1.67 million in 2012. The highest incremental cost
      effectiveness ratio was for the cost per beneficiary covered including CHW
      salaries, estimated at US$47.12 for 2010-2011. The smallest incremental cost
      effectiveness ratio was for the cost per household visit not including CHW
      salaries, estimated at US$0.09 for 2010-2012. Adding CHW salaries would not only
      have increased total program costs by 362% in 2012 but also led to the largest
      efficiency gains in program implementation; a 56% gain in cost per output in the
      long run as compared with the short run after including CHW salaries.
      CONCLUSIONS: Our findings can be used to inform future CHW program policy both in
      Mozambique and in other countries, as well as provide a set of incremental cost
      per output measures to be used in benchmarking to other CHW costing analyses.

PMID- 25858900
TI  - Evaluating the performance of a screening test for depression in primary care.

PMID- 25858901
TI  - Facemasks for the prevention of infection in healthcare and community settings.
AB  - Facemasks are recommended for diseases transmitted through droplets and
      respirators for respiratory aerosols, yet recommendations and terminology vary
      between guidelines. The concepts of droplet and airborne transmission that are
      entrenched in clinical practice have recently been shown to be more complex than
      previously thought. Several randomised clinical trials of facemasks have been
      conducted in community and healthcare settings, using widely varying
      interventions, including mixed interventions (such as masks and handwashing), and
      diverse outcomes. Of the nine trials of facemasks identified in community
      settings, in all but one, facemasks were used for respiratory protection of well
      people. They found that facemasks and facemasks plus hand hygiene may prevent
      infection in community settings, subject to early use and compliance. Two trials
      in healthcare workers favoured respirators for clinical respiratory illness. The
      use of reusable cloth masks is widespread globally, particularly in Asia, which
      is an important region for emerging infections, but there is no clinical research
      to inform their use and most policies offer no guidance on them. Health economic
      analyses of facemasks are scarce and the few published cost effectiveness models
      do not use clinical efficacy data. The lack of research on facemasks and
      respirators is reflected in varied and sometimes conflicting policies and
      guidelines. Further research should focus on examining the efficacy of facemasks
      against specific infectious threats such as influenza and tuberculosis, assessing
      the efficacy of cloth masks, investigating common practices such as reuse of
      masks, assessing compliance, filling in policy gaps, and obtaining cost
      effectiveness data using clinical efficacy estimates. 

PMID- 25858902
TI  - Perspectives on progress: using genomics to guide clinical therapy.

PMID- 25858903
TI  - China lays out bold plan to improve healthcare.

PMID- 25858904
TI  - Treatment results of image-guided high-dose-rate interstitial brachytherapy for
      pelvic recurrence of uterine cancer.
AB  - PURPOSE: We analyzed clinical data to evaluate the effectiveness of image-guided
      high-dose-rate interstitial brachytherapy (HDR-ISBT) for pelvic recurrence of
      uterine cancer. METHODS AND MATERIALS: Between 2003 and 2011, 56 patients were
      treated with HDR-ISBT with or without external beam radiotherapy (EBRT). The
      median followup time was 33 months (range, 1-109 months). Pre-ISBT treatments
      included radical hysterectomy for 35 patients (Group A), radical hysterectomy
      with postoperative radiotherapy for 8 patients (Group B), and radical
      radiotherapy for 13 patients (Group C). We initiated MRI-assisted CT-based
      planning for the last 49 patients. The median ISBT single fraction dose was 6 Gy.
      The median total doses were 30 and 54 Gy with and without EBRT (range, 30-50 Gy)
      for Group A, respectively and 48 Gy without EBRT for Groups B and C. RESULTS: The
      3-year local control (LC) rates were 85%, 75%, and 46% for Groups A, B, and C,
      respectively (p = 0.017). The 3-year LC rates were 84%, 73%, and 33% for clinical
      target volume at the time of HDR-ISBT of <10, 10-29, and >=30 cc, respectively (p
      = 0.005). The 3-year LC results tended to be higher for patients whose D100
      (clinical target volume) was equal or higher than 67.1 Gy (p = 0.098). A total of
      13 late complications of Grades 3-5 occurred in 11 patients (20%). CONCLUSIONS:
      Our image-guided HDR-ISBT for pelvic recurrence of uterine cancer provided good
      treatment outcomes. The treatment results for patients who underwent radical
      surgery with or without postoperative radiotherapy are better than those for
      patients who underwent radical radiotherapy.

PMID- 25858905
TI  - Endotracheal brachytherapy alone: An effective palliative treatment for tracheal
      tumors.
AB  - BACKGROUND: Tracheal tumors are rare. They are usually unresectable and treated
      primarily with external beam radiation. The use of palliative endotracheal
      brachytherapy (ETBT) alone in treating patients with tracheal tumors has not been
      reported. METHODS: Using a prospective database, demographic, treatment, and
      outcome data of patients with tracheal tumors treated palliatively with ETBT from
      2006 to 2014 were analyzed. Tumor and symptom responses were evaluated based on
      response evaluation criteria in solid tumors criteria. Survival, in-field disease
      control, symptom response, and duration of symptom responses were evaluated using
      descriptive analyses. RESULTS: Sixteen ETBT (median, 2) treatments were delivered
      to 8 patients. Median age was 63.4 years old. Common symptoms were hemoptysis,
      cough, and dyspnea. Tracheal lengths of 3.5-11 cm were treated with 5-7
      Gy/fraction, using 1-3 fractions. The mean overall survival was 5 months and
      symptom-free survival was 6.8 months, respectively. After ETBT, 88% of patients
      experienced symptomatic improvement (hemoptysis [n = 3/3], cough [n = 6/7], and
      dyspnea [n = 4/4]). One patient developed Grade 1 stenosis that did not require
      intervention. CONCLUSIONS: This is among the largest series of tracheal tumors
      treated palliatively with ETBT alone. ETBT provided effective palliation with
      symptom improvement and minimal toxicity.

PMID- 25858907
TI  - Paediatric neurologist's suspension may affect 50 birth damage cases in which he
      was an expert witness.

PMID- 25858906
TI  - Impact of emotional distress on caregivers burden among Nigerian children with
      Obstructive Adenotonsillar hypertrophy.
AB  - BACKGROUND: Despite the significance of the role of caregivers among children
      with Obstructive Adenotonsillar hypertrophy (OAT), their caregiving experience
      and emotional well-being are given poor attention in research, policy and service
      design. This study represents a novel effort sought to investigate the burden
      experienced by caregivers of children with OAT and the impact of emotional
      distress on their caregiving burden. METHODOLOGY: A total of one hundred
      consecutive caregivers of children with OAT were interviewed with designed socio
      demographic questionnaire. This was subsequently followed by administration of
      General Health Questionnaire-12 (GHQ-12) to ascertain emotional distress using
      cut-off score >= 3 and Zarit Caregivers Burden of care scale was used to
      characterize the pattern of burden experienced by these caregivers. RESULTS: In
      this study, the mean ages of children with OAT and their caregivers were 36.7(+/-
      21.8) months and 34.4(+/- 5.4) years, respectively. The affected children were
      mainly males (68%), while their caregivers were predominantly females (84%).
      Fifty-seven percent of children with OAT were schooling but 13% of them had
      academic delay. Majority of the caregivers (66%) had a tertiary level of
      education. Of the total participants, up to 43% reported various degrees of
      burden of care, with majority (34%) of them reporting mild to moderate burden of
      care. In the same vein, 48% were emotionally distressed. Following regression
      analyses, emotional distress was independently associated with burden of care
      among participants (Odds ratio [OR]=0.108; 95% Confidence Interval [95% CI]=0.043
      0.272; p < 0.001). CONCLUSION: Caregivers of children with OAT reported the
      experience of various degrees of burden, and worse among caregivers with
      emotional distress. Overall, the level of distress and burden observed in this
      study were many-fold what has been reported among caregivers of other populations
      of children. The results of this study support the proposal of proactive measures
      to address the psychosocial needs of caregivers as integral to the care of
      children with OAT. Further research on the well-being of caregivers is also
      justified.

PMID- 25858908
TI  - A good night for a bad day.

PMID- 25858910
TI  - What do you think should be the political priorities for the NHS?

PMID- 25858909
TI  - A randomised controlled trial of small particle inhaled steroids in refractory
      eosinophilic asthma (SPIRA).
AB  - BACKGROUND: Some patients with refractory asthma have evidence of uncontrolled
      eosinophilic inflammation in the distal airways. While traditional formulations
      of inhaled steroids settle predominantly in the large airways, newer formulations
      with an extra-fine particle size have a more peripheral pattern of deposition.
      Specifically treating distal airway inflammation may improve asthma control.
      METHODS: 30 patients with refractory asthma despite high dose inhaled
      corticosteroids were identified as having persistent airway eosinophilia.
      Following 2 weeks of prednisolone 30 mg, patients demonstrating an improvement in
      asthma control were randomised to receive either ciclesonide 320 ug twice daily
      or placebo in addition to usual maintenance therapy for 8 weeks. The primary
      outcome measure was sputum eosinophil count at week 8. Alveolar nitric oxide was
      measured as a marker of distal airway inflammation. RESULTS: There was continued
      suppression of differential sputum eosinophil counts with ciclesonide (median
      2.3%) but not placebo (median 4.5%) though the between-group difference was not
      significant. When patients who had changed their maintenance prednisolone dose
      during the trial were excluded the difference between groups was significant
      (1.4% vs 4.5%, p=0.028). Though alveolar nitric oxide decreased with ciclesonide
      the value did not reach statistical significance. CONCLUSIONS: These data
      demonstrate that patients with ongoing eosinophilic inflammation are not truly
      refractory, and that suppression of airway eosinophilia may be maintained with
      additional inhaled corticosteroid. Further work is needed with a focus on patient
      orientated outcome measures such as exacerbation rate, with additional tests of
      small airway function. TRIAL REGISTRATION NUMBER: NCT01171365. Protocol available
      at http://www.clinicaltrials.gov.

PMID- 25858911
TI  - Comparative Risks of Aldehyde Constituents in Cigarette Smoke Using Transient
      Computational Fluid Dynamics/Physiologically Based Pharmacokinetic Models of the
      Rat and Human Respiratory Tracts.
AB  - Computational fluid dynamics (CFD) modeling is well suited for addressing species
      specific anatomy and physiology in calculating respiratory tissue exposures to
      inhaled materials. In this study, we overcame prior CFD model limitations to
      demonstrate the importance of realistic, transient breathing patterns for
      predicting site-specific tissue dose. Specifically, extended airway CFD models of
      the rat and human were coupled with airway region-specific physiologically based
      pharmacokinetic (PBPK) tissue models to describe the kinetics of 3 reactive
      constituents of cigarette smoke: acrolein, acetaldehyde and formaldehyde.
      Simulations of aldehyde no-observed-adverse-effect levels for nasal toxicity in
      the rat were conducted until breath-by-breath tissue concentration profiles
      reached steady state. Human oral breathing simulations were conducted using
      representative aldehyde yields from cigarette smoke, measured puff ventilation
      profiles and numbers of cigarettes smoked per day. As with prior steady-state
      CFD/PBPK simulations, the anterior respiratory nasal epithelial tissues received
      the greatest initial uptake rates for each aldehyde in the rat. However,
      integrated time- and tissue depth-dependent area under the curve (AUC)
      concentrations were typically greater in the anterior dorsal olfactory epithelium
      using the more realistic transient breathing profiles. For human simulations,
      oral and laryngeal tissues received the highest local tissue dose with greater
      penetration to pulmonary tissues than predicted in the rat. Based upon lifetime
      average daily dose comparisons of tissue hot-spot AUCs (top 2.5% of surface area
      normalized AUCs in each region) and numbers of cigarettes smoked/day, the order
      of concern for human exposures was acrolein > formaldehyde > acetaldehyde even
      though acetaldehyde yields were 10-fold greater than formaldehyde and acrolein. 

PMID- 25858912
TI  - Allelic Imbalance Is a Prevalent and Tissue-Specific Feature of the Mouse
      Transcriptome.
AB  - In mammals, several classes of monoallelic genes have been identified, including
      those subject to X-chromosome inactivation (XCI), genomic imprinting, and random
      monoallelic expression (RMAE). However, the extent to which these epigenetic
      phenomena are influenced by underlying genetic variation is unknown. Here we
      perform a systematic classification of allelic imbalance in mouse hybrids derived
      from reciprocal crosses of divergent strains. We observe that deviation from
      balanced biallelic expression is common, occurring in ~20% of the mouse
      transcriptome in a given tissue. Allelic imbalance attributed to genotypic
      variation is by far the most prevalent class and typically is tissue-specific.
      However, some genotype-based imbalance is maintained across tissues and is
      associated with greater genetic variation, especially in 5' and 3' termini of
      transcripts. We further identify novel random monoallelic and imprinted genes and
      find that genotype can modify penetrance of parental origin even in the setting
      of large imprinted regions. Examination of nascent transcripts in single cells
      from inbred parental strains reveals that genes showing genotype-based imbalance
      in hybrids can also exhibit monoallelic expression in isogenic backgrounds. This
      surprising observation may suggest a competition between alleles and/or reflect
      the combined impact of cis- and trans-acting variation on expression of a given
      gene. Our findings provide novel insights into gene regulation and may be
      relevant to human genetic variation and disease. 

PMID- 25858913
TI  - Genetic screening could improve breast cancer prevention, study finds.

PMID- 25858914
TI  - High INR on warfarin.

PMID- 25858917
TI  - Correction.
AB  - Demey D, Berrington A, Evandrou M, et al. Living alone and psychological well
      being in mid-life: does partnership history matter?. J Epidemiol Community Health
      2014;68:410. This article now includes the CC BY-NC licence. J

PMID- 25858915
TI  - STATE TRANSITION7-Dependent Phosphorylation Is Modulated by Changing
      Environmental Conditions, and Its Absence Triggers Remodeling of Photosynthetic
      Protein Complexes.
AB  - In plants and algae, the serine/threonine kinase STN7/STT7, orthologous protein
      kinases in Chlamydomonas reinhardtii and Arabidopsis (Arabidopsis thaliana),
      respectively, is an important regulator in acclimation to changing light
      environments. In this work, we assessed STT7-dependent protein phosphorylation
      under high light in C. reinhardtii, known to fully induce the expression of light
      harvesting complex stress-related protein3 (LHCSR3) and a nonphotochemical
      quenching mechanism, in relationship to anoxia where the activity of cyclic
      electron flow is stimulated. Our quantitative proteomics data revealed numerous
      unique STT7 protein substrates and STT7-dependent protein phosphorylation
      variations that were reliant on the environmental condition. These results
      indicate that STT7-dependent phosphorylation is modulated by the environment and
      point to an intricate chloroplast phosphorylation network responding in a highly
      sensitive and dynamic manner to environmental cues and alterations in kinase
      function. Functionally, the absence of the STT7 kinase triggered changes in
      protein expression and photoinhibition of photosystem I (PSI) and resulted in the
      remodeling of photosynthetic complexes. This remodeling initiated a pronounced
      association of LHCSR3 with PSI-light harvesting complex I (LHCI)-ferredoxin-NADPH
      oxidoreductase supercomplexes. Lack of STT7 kinase strongly diminished PSII-LHCII
      supercomplexes, while PSII core complex phosphorylation and accumulation were
      significantly enhanced. In conclusion, our study provides strong evidence that
      the regulation of protein phosphorylation is critical for driving successful
      acclimation to high light and anoxic growth environments and gives new insights
      into acclimation strategies to these environmental conditions.

PMID- 25858918
TI  - Acute penile pain and swelling in a 4-year-old child with Henoch-Schonlein
      purpura.
AB  - Henoch-Schonlein purpura (HSP) is the most common vasculitis found in children.
      It usually affects the small vessels of the skin, joints, gastrointestinal tract
      and, more rarely, kidneys, brain, lungs and genitalia. Apart from classical
      presentation with purpuric rashes around buttocks and lower extremities, features
      such as arthralgia, abdominal pain, haematuria and proteinuria as well as scrotal
      swelling have been described in the literature. Penile involvement is rare and is
      not commonly described. We describe a child with HSP who developed penile
      involvement. We review the literature of all the cases reported in detail, in
      order to highlight useful clinical presentation, management and prognosis of this
      rare manifestation. 

PMID- 25858916
TI  - SOS2-LIKE PROTEIN KINASE5, an SNF1-RELATED PROTEIN KINASE3-Type Protein Kinase,
      Is Important for Abscisic Acid Responses in Arabidopsis through Phosphorylation
      of ABSCISIC ACID-INSENSITIVE5.
AB  - Abscisic acid (ABA) plays an essential role in seed germination. In this study,
      we demonstrate that one SNF1-related protein kinase3-type protein kinase, SOS2
      like protein kinase5 (PKS5), is involved in ABA signal transduction via the
      phosphorylation of an interacting protein, abscisic acid-insensitive5 (ABI5). We
      found that pks5-3 and pks5-4, two previously identified PKS5 superactive kinase
      mutants with point mutations in the PKS5 FISL/NAF (a conserved peptide that is
      necessary for interaction with SOS3 or SOS3-like calcium binding proteins) motif
      and the kinase domain, respectively, are hypersensitive to ABA during seed
      germination. PKS5 was found to interact with ABI5 in yeast (Saccharomyces
      cerevisiae), and this interaction was further confirmed in planta using
      bimolecular fluorescence complementation. Genetic studies revealed that ABI5 is
      epistatic to PKS5. PKS5 phosphorylates a serine (Ser) residue at position 42 in
      ABI5 and regulates ABA-responsive gene expression. This phosphorylation was
      induced by ABA in vivo and transactivated ABI5. Expression of ABI5, in which Ser
      42 was mutated to alanine, could not fully rescue the ABA-insensitive phenotypes
      of the abi5-8 and pks5-4abi5-8 mutants. In contrast, mutating Ser-42 to aspartate
      rescued the ABA insensitivity of these mutants. These data demonstrate that PKS5
      mediated phosphorylation of ABI5 at Ser-42 is critical for the ABA regulation of
      seed germination and gene expression in Arabidopsis (Arabidopsis thaliana).

PMID- 25858919
TI  - Family as the primary caregiver: palliative care in the Golan Heights.
AB  - Palliative care is recognised by the WHO as an essential component of care for
      the seriously ill. Geographically isolated and historically underserved
      communities, particularly from ethnic minority groups, face obstacles in
      obtaining adequate palliative care. This case involves the care of a 26-year-old
      Druze man suffering from a terminal cancer in his Golan Heights village. Local
      physicians were able to train the patient's father in a palliative care capacity.
      In the effort of capacity building, the physician and palliative care team also
      aided the aggrieved family in the process of coping. Robust support networks,
      both at state and community levels, facilitated the care provided. In showcasing
      the role of the national and local safety net in activating and building
      community resources to address a dearth of palliative care services in
      disadvantaged regions, this case models a potentially effective community-based
      approach to palliative care for patients from underserved populations. 

PMID- 25858920
TI  - Autoimmune pancreatitis mimicking Klatskin tumour on radiology.
AB  - Autoimmune pancreatitis (AIP) is categorised into two distinct types, AIP type 1
      and 2. Although there can be multisystem involvement, rarely, the cholangitis
      associated with AIP can present radiologically in a manner similar to that of
      Klatskin tumour. We present the case of a 65-year-old man who was almost
      misdiagnosed with a Klatskin tumour because of the similarity in radiological
      features of the two aforementioned clinical entities. The patient presented with
      a history of jaundice, pruritus and abdominal pain, and work up showed deranged
      liver function tests, elevated cancer antigen 19-9 levels and positive
      antinuclear antibodies. CT scan of the abdomen showed findings suggestive of
      Klatskin tumour but due to diffuse enlargement of the pancreas and surrounding
      low-attenuation halo found on a closer review, a diagnosis of AIP was performed.
      The patient was started on standard corticosteroid therapy and responded well,
      with complete resolution of the radiological findings. 

PMID- 25858921
TI  - Complicated septic arthritis after knee arthroscopy in a 75-year-old man with
      osteoarthritis and a popliteal cyst.
AB  - A 75-year-old man presented in shock secondary to septic arthritis of the knee.
      The patient, with a known history of knee osteoarthritis, was treated elsewhere
      for mechanical locking symptoms and effusion with arthroscopic debridement, and
      developed septic arthritis, which disseminated to the leg and foot after a tear
      in the capsule, and a ruptured pyogenic popliteal cyst. Open debridement of the
      knee joint, and drainage of the abscesses of the leg and foot, were performed.
      Antibiotic-loaded cement beads were left in the residual space. Debridement was
      repeated and cement beads removed after 4 days, and finally the infection was
      eradicated without any serious consequences for the patient. There is debate over
      arthroscopic intervention for osteoarthritic knees. The presence of a popliteal
      cyst, which is a rather common finding in the latter, could be related to a
      significant number of complications, such as septic arthritis.

PMID- 25858922
TI  - Treasure in the chest.
AB  - A 41-year-old woman with a background of asthma was preparing for a party on New
      Year's Eve when she developed a mild wheeze. Concerned her symptoms would develop
      and impact on festivities, she located her uncapped salbutamol inhaler in her
      handbag. Ignoring the coarse rattle as she shook it, she proceeded to take a deep
      inspiration. Instantly, she felt a painful scratch in her pharynx followed by a
      harsh cough, which persisted over the next few minutes and became associated with
      haemoptysis. She was taken to the accident and emergency department. Chest X-ray
      revealed a radiodense foreign body in the distal right main bronchus. During
      endoscopy, an earring, causing subtotal occlusion in the right lower lobe
      bronchus was found and extracted. Her observations remained within normal limits
      throughout. The importance of replacing caps on inhalers when not in use is
      illustrated and should be encouraged when inhaler technique is taught or
      reviewed. 

PMID- 25858923
TI  - Autotransplantation for the management of ketamine ureteritis.
AB  - Ketamine-associated cystitis is a well-recognised syndrome; yet upper urinary
      tract involvement remains poorly understood. We present the case of a 33-year-old
      man who developed ketamine-associated cystitis and ureteritis. The patient's
      severe bladder symptoms required subtotal cystectomy and orthotopic
      reconstruction. However, the associated ureteritis led to bilateral ureteric
      obstruction and renal failure. Bilateral autotransplantation with
      pyelovesicostomy was performed. This first case of autotransplantation for
      ketamine uropathy helps to demonstrate the potentially devastating effects of
      ketamine on the urinary tract. 

PMID- 25858924
TI  - Severe thrombocytopenia and recurrent epistaxis associated with primary Epstein
      Barr virus infection.
AB  - Infectious mononucleosis, caused by the Epstein-Barr virus (EBV), generally
      follows a benign, yet protracted course, with the majority of symptoms being
      systemic somatic symptoms. Rarely, the clinical picture can be complicated by
      more acute severe haemotological sequelae of the disease, requiring
      hospitalisation and causing diagnostic uncertainty, particularly when
      distinguishing between a viral illness and a lymphoproliferative disorder. We
      describe the case of a young male patient who presented with headache, recurrent
      epistaxis and severe thrombocytopenia. 

PMID- 25858925
TI  - Group A streptococcal endophthalmitis complicating a sore throat in a 2-year-old
      child.
AB  - A previously well 2-year-old presented to her general practitioner after 5 days
      of fever, lethargy, sore throat and a slightly red eye. A viral infection was
      diagnosed. Two days later, she re-presented with a swollen right eyelid and a
      moderately red eye. Oral amoxicillin and chloramphenicol eye drops were
      prescribed. The next day, marked periorbital swelling developed. She was admitted
      to hospital and parenteral ceftriaxone was started. Examination under anaesthetic
      showed injected globe diffuse corneal clouding and peripheral corneal opacities;
      ultrasound and CT suggested endophthalmitis. On transfer to a tertiary centre,
      intraocular vancomycin and subconjunctival cefuroxime were given. Aqueous fluid
      samples were positive for group A Streptococcus (GAS) by PCR, so parenteral
      clindamycin was added. GAS endophthalmitis was confirmed 1 day later from the
      positive intraocular fluid culture results. Visual evoked potentials revealed
      complete loss of vision. The eye was removed to limit potential spread. She made
      a good recovery postoperatively and was discharged on oral antibiotics.

PMID- 25858926
TI  - Femoral hernia, a rare complication following deep inguinal lymph node
      dissection.
AB  - A 72-year-old woman underwent complete deep inguinal lymph node dissection on her
      right side subsequent to metastasis from malignant melanoma. On the second
      postoperative day, the patient reported of nausea and vomiting. She presented
      with a mass in the resected area that gradually increased in size to
      approximately 15*20 cm. The wound was opened a few hours after onset of symptoms
      and a large femoral hernia with 40 cm of small intestine was immediately revealed
      protruding in the groin. Prophylactic suturing of the inguinal ligament and
      Coopers ligament can reduce the risk of postoperative femoral hernia. Further,
      the authors argue that drainage for seroma and haematoma should be performed with
      utmost care, considering other possible causes and, if necessary, guided by
      ultrasonography.

PMID- 25858928
TI  - Mucoepidermoid carcinoma of oral mucosa.

PMID- 25858927
TI  - Granulomatous interstitial pneumonia induced by the intake of rice bran pickles:
      a rare subtype of pulmonary manifestation associated with food allergy.
AB  - Pulmonary manifestations associated with food allergy are rich in variety. We
      report the first case of food-induced granulomatous interstitial pneumonia
      mimicking hypersensitivity pneumonitis (HP). A 77-year-old woman with respiratory
      symptoms was referred to our hospital. We performed a surgical lung biopsy, which
      showed the features of granulomatous interstitial pneumonia. Her clinical history
      resembled those observed in HP. However, avoidance of exposure to the causative
      antigens did not improve her symptoms. Moreover, the patient had some features
      inconsistent with HP, such as elevated serum IgE levels, blood eosinophilia,
      intrathoracic lymphadenopathies and pleural effusion. Therefore, we pursued
      another extrinsic non-inhaled antigen as the cause of pulmonary involvements. We
      noted that she had been eating homemade rice bran pickles, and pulmonary
      involvements were induced by an ingestion challenge test. We suggest that
      granulomatous interstitial pneumonia may be a rare subtype of the pulmonary
      manifestations associated with food allergy. 

PMID- 25858929
TI  - Proximal-type epithelioid sarcoma-unusual presentation: unilateral vulvar mass.
AB  - Epithelioid sarcoma of the vulva is a very rare malignant soft tissue tumour,
      usually initially asymptomatic, which simulates a variety of benign lesions,
      leading to diagnosis only at later stages. Prognosis is generally poor. We report
      a case of a 55-year-old postmenopausal woman, who presented with rapid growth of
      an asymptomatic mass located in the left labia majora. Biopsy of the lesion
      revealed features characteristic of proximal-type epithelioid sarcoma.
      Ganglionar, adrenal, pulmonary and hepatic metastases were found at
      thoracoabdominopelvic CT scan. During hospitalisation, the patient's clinical
      condition suffered rapid deterioration and she died on the 16th day of admission.

PMID- 25858930
TI  - Colonic phytobezoar as a rare cause of large bowel obstruction.
AB  - Bezoars are masses formed by the concretion of stomach contents or debris within
      the gastrointestinal tract. Bezoars are rare and account for only 0.4-4% of all
      cases of gastrointestinal obstruction and mainly occur in the stomach or small
      intestine. Intestinal obstruction caused by colonic bezoars is extremely rare. We
      report a case of a distal sigmoid obstruction caused by a phytobezoar in a 60
      year-old man with no obvious precipitating causes. He presented to the emergency
      department acutely unwell and a subsequent abdominal CT scan showed a mass within
      the proximal sigmoid colon suspicious for a bezoar. He proceeded to have an
      urgent laparotomy and the obstructive intraluminal mass in the sigmoid colon was
      identified and manually broken down. Subsequent histopathological assessment
      reported amorphous material and plant cellular matter consistent with the
      diagnosis of a phytobezoar. 

PMID- 25858931
TI  - Stress-induced cardiomyopathy.
AB  - A woman in her early 70s presented with chest pain, dyspnoea and diaphoresis 30
      min after her husband expired in our hospital. Cardiac markers were elevated and
      there were acute changes in ECG suggestive for acute coronary syndrome.
      Echocardiogram showed apical akinesis, basal segment hyperkinesis with an
      ejection fraction of 30%. Cardiac catheterisation was performed showing non
      obstructive coronary arteries, leading to the diagnosis of stress-induced
      cardiomyopathy. The patient improved with medical management. Repeat
      echocardiogram 2 months later showed resolution of heart failure with an ejection
      fraction of 65-70%.

PMID- 25858932
TI  - Not all secondary bone tumours are secondaries. Concurrent metastatic breast
      carcinoma and chondrosarcoma of the femur.
AB  - We present a case of metastatic adenocarcinoma of the breast in a patient who
      sustained a pathological fracture of the distal femur. Histology of the distal
      femur lesion excised at the time of endoprosthetic replacement confirmed this to
      be a primary chondrosarcoma. We have reviewed the literature and identified
      previously documented cases of concurrent breast carcinoma and chondrosarcoma of
      bone. A high index of suspicion is warranted and the diagnosis must be first
      confirmed before rushing to internal fixation (therapeutic or prophylactic)
      assuming them to be secondary bone lesions from the known primary cancer even in
      patients with multiple metastases. 

PMID- 25858933
TI  - Delayed diagnosis of angiosarcoma of the spleen: clinically presenting as
      recurrent haemoperitoneum following embolisation.
AB  - Angiosarcoma is a highly aggressive and extremely rare neoplasm of the spleen,
      with a limited number of reported cases worldwide. We report a case of a 69-year
      old man who presented with progressive symptoms of fatigue, abdominal and back
      pain, anaemia and haemoperitoneum 1 year following embolisation of the spleen for
      splenic rupture. Additional imaging and colonoscopy with biopsy revealed intra
      abdominal fluid and a colonic adenocarcinoma. Diagnostic laparoscopy demonstrated
      a haemoperitoneum and colon carcinoma, after which splenectomy via laparotomy was
      performed. Pathology report revealed an angiosarcoma of the spleen with
      peritoneal tumour deposits. Rupturing of a spleen may be due to an underlying
      disease. Therefore, the differential diagnosis of splenic rupture should include
      the possibility of a splenic tumour. The definitive diagnosis and treatment of a
      splenic angiosarcoma may require splenectomy, although prognosis is poor.

PMID- 25858934
TI  - Diffuse unresolving pulmonary nodules in a patient with a history of cervical
      carcinoma.

PMID- 25858935
TI  - Leucocyte adhesion deficiency type 1 with developmental delay secondary to CMV
      infection and filiation questions.
AB  - Leucocyte adhesion deficiency (LAD) is a group of rare autosomal recessive (<1:1
      000 000 births) inherited disorders characterised by immune deficiency and
      peripheral neutrophilia. Three types of LAD syndrome have been distinguished. LAD
      type 1 (LAD-I) is the most common. It results from a mutation in the integrin
      beta 2 (ITGB2) gene that codes the ITGB subunit (CD18 antigen). Since 1970, it
      has been reported in more than 300 children worldwide. It is characterised by
      delayed separation of the umbilical cord, recurrent bacterial and fungal
      infections, defective wound healing, blood neutrophilia and a high mortality rate
      at an early age. We report the second fatal case of an infant with LAD-I
      diagnosed in Chile, with developmental delay associated with a congenital
      cytomegalovirus infection. CD18/CD11 expression was normal. Genetic analysis of
      CD18 revealed a homozygous mutation in ITGB2, viz.c.1835G>T; p.C612F, and led us
      to suspect a biological parent other than the legal father and, therefore, an
      unwanted social situation.

PMID- 25858936
TI  - Chemotherapy-induced acute psychosis in a patient with malignant germ cell
      tumour.
AB  - A 25-year-old Thai woman with ovarian germ cell tumour presented with behavioural
      changes after receiving an intensive dose of neoadjuvant chemotherapy with
      bleomycin, etoposide and cisplatin, for a relapse. Her initial symptoms of mood
      fluctuation and insomnia were noticed while hospitalised for the third cycle, and
      became more severe. She was very irritable, highly distracted and forgetful. She
      exhibited flights of ideas and hyperactivity, including compulsive shopping. She
      also had paranoid ideations, auditory hallucinations, and thoughts of being
      wealthy and close to the prime minister. She was not depressed. She was diagnosed
      with axis I psychotic disorder not otherwise specified. The incremental dosage of
      olanzapine from 5 to 20 mg/day was given but failed to control her psychotic
      symptoms during the first week, and was therefore switched to risperidone. At 4
      mg/day, her symptoms were dramatically controlled. This novel evidence suggests
      the rare possibility of an association between chemotherapy and the development
      of psychotic attacks.

PMID- 25858937
TI  - Unusual presentation of uterine leiomyoma.
AB  - Uterine leiomyoma is the most common pelvic tumour in women. The presentation of
      uterine leiomyoma varies. Symptoms may include abnormal uterine bleeding or
      abdominal pressure and heaviness; however, most cases are asymptomatic. We report
      a case with renal impairment as the first presentation of uterine leiomyoma in a
      patient who presented with extensive bilateral lower limb oedema and no menstrual
      symptoms. Imaging studies, a subsequent Papanicolaou test and uterine biopsy were
      suggestive of uterine leiomyoma, which was confirmed by pathological examination
      after hysterectomy. The patient's kidney impairment resolved completely after the
      procedure. 

PMID- 25858938
TI  - Primary clear cell carcinoma of the rete testis: 1st report.
AB  - Primary tumours of the rete testis, either benign or malignant, are very rare.
      Such lesions require careful scrutiny including immunohistochemical analysis to
      exclude malignant lesions such as mesothelioma or papillary serous carcinoma. To
      the best of our knowledge this is the first report of a primary clear cell
      carcinoma of the rete testis. The possibility of a primary renal cell carcinoma
      or other primary site with metastatic spread to rete testis was excluded by
      thorough clinical and radiological work-up. 

PMID- 25858939
TI  - Variability in the international normalised ratio (INR) in patients with
      antiphospholipid syndrome and positive lupus anticoagulant: should the INR
      targets be higher?
AB  - We present the case of a 34-year-old woman with a history of antiphospholipid
      syndrome with triple positivity for antiphospholipid antibodies, who had multiple
      thrombotic events, predominantly pulmonary embolic events, despite treatment with
      enoxaparin. She is currently on warfarin, with which she has been adequately
      controlled most of the time, presenting with only one haemorrhagic event
      consisting of haematuria and prolonged international normalised ratio (INR)
      without bleeding. This kind of patient represents a challenge for clinicians,
      particularly due to INR therapeutic targets, which should be higher than
      recommended in other patients due to the lupus anticoagulant positivity. 

PMID- 25858940
TI  - Carcinoma pancreas and fibrocalcific pancreatic diabetes: a dual association for
      weight loss.

PMID- 25858941
TI  - Pituitary apoplexy presenting with anorexia and hyponatraemia.
AB  - Pituitary apoplexy, a syndrome caused by haemorrhage into the pituitary gland,
      typically manifests as sudden severe headache, visual symptoms and
      hypopituitarism, including adrenal insufficiency. We report a case of a 65-year
      old man with adrenal insufficiency due to pituitary apoplexy presenting with
      anorexia following temporal headache and diagnosed through evaluation for
      hyponatraemia. MRI focusing on the pituitary gland helped to confirm the
      diagnosis. Our experience serves as a useful reminder of this atypical
      presentation of pituitary apoplexy, also known as 'subclinical pituitary
      apoplexy,' and underscores the importance of careful evaluation for hyponatraemia
      using serial urine osmolality, which is useful to distinguish hypovolaemic
      hyponatraemia from euvolaemic hyponatraemia. Clinicians should consider pituitary
      apoplexy as a differential diagnosis in cases of anorexia, loss of energy or
      hyponatraemia, following headache even when the patient is lacking classical
      symptoms such as severe headache or visual symptoms. 

PMID- 25858942
TI  - A rare combination of facial and hypoglossal nerve palsies following post
      traumatic internal carotid artery dissection.

PMID- 25858943
TI  - Giant cell arteritis mimicking infiltrative leptomeningeal disease of the optic
      nerves.
AB  - A 67-year-old man presented with several days of progressive, painless left eye
      vision loss. He reported mild jaw claudication but denied headache, scalp
      tenderness or constitutional symptoms. Examination revealed palpable temporal
      arteries, blurring of the left optic disc, and 20/100 vision in the left eye with
      mild relative afferent pupillary defect. Inflammatory markers were sent, and
      methylprednisolone was initiated for presumptive giant cell arteritis (GCA).
      Erythrocyte sedimentation rate was normal, however, and C reactive protein was
      only mildly elevated, prompting further investigation. Orbital MRI revealed
      nodular enhancement of the optic nerve sheaths bilaterally from optic nerve head
      to chiasm, raising concern for an infiltrative leptomeningeal process such as
      sarcoidosis or lymphoma. Methylprednisolone was temporarily stopped while a broad
      work up for inflammatory and neoplastic causes was pursued. Fluorodeoxyglucose
      positron emission tomography ultimately revealed hypermetabolism in the temporal,
      ophthalmic and occipital arteries suggesting GCA, which was confirmed by temporal
      artery biopsy. Steroids were restarted, and the patient's vision stabilised. 

PMID- 25858944
TI  - A hot, swollen joint without trauma: septic arthritis until proven otherwise.

PMID- 25858945
TI  - Horner syndrome after radical neck surgery for anaplastic thyroid carcinoma.

PMID- 25858946
TI  - Thyroglossal duct cyst presenting as a large isolated mass within the middle
      mediastinum.

PMID- 25858947
TI  - Pregnancy in a patient with Schwachman-Diamond syndrome.
AB  - We present the case of a 26-year-old Caucasian woman with Schwachman-Diamond
      syndrome with regard to her obstetric and gynaecology requirements, and in
      particular to her antenatal care across two pregnancies. 

PMID- 25858948
TI  - Utility of transbronchial lung biopsy in diagnosis of cavitary lung lesion in a
      patient with HIV infection.

PMID- 25858949
TI  - Urethral diverticulum: a potential hazard of penile clamp application for male
      urinary incontinence.

PMID- 25858950
TI  - An unusual pelvic cyst found at laparoscopic hernia repair.

PMID- 25858951
TI  - Optimizing sparse sequencing of single cells for highly multiplex copy number
      profiling.
AB  - Genome-wide analysis at the level of single cells has recently emerged as a
      powerful tool to dissect genome heterogeneity in cancer, neurobiology, and
      development. To be truly transformative, single-cell approaches must affordably
      accommodate large numbers of single cells. This is feasible in the case of copy
      number variation (CNV), because CNV determination requires only sparse sequence
      coverage. We have used a combination of bioinformatic and molecular approaches to
      optimize single-cell DNA amplification and library preparation for highly
      multiplexed sequencing, yielding a method that can produce genome-wide CNV
      profiles of up to a hundred individual cells on a single lane of an Illumina
      HiSeq instrument. We apply the method to human cancer cell lines and biopsied
      cancer tissue, thereby illustrating its efficiency, reproducibility, and power to
      reveal underlying genetic heterogeneity and clonal phylogeny. The capacity of the
      method to facilitate the rapid profiling of hundreds to thousands of single-cell
      genomes represents a key step in making single-cell profiling an easily
      accessible tool for studying cell lineage.

PMID- 25858953
TI  - All-atom 3D structure prediction of transmembrane beta-barrel proteins from
      sequences.
AB  - Transmembrane beta-barrels (TMBs) carry out major functions in substrate
      transport and protein biogenesis but experimental determination of their 3D
      structure is challenging. Encouraged by successful de novo 3D structure
      prediction of globular and alpha-helical membrane proteins from sequence
      alignments alone, we developed an approach to predict the 3D structure of TMBs.
      The approach combines the maximum-entropy evolutionary coupling method for
      predicting residue contacts (EVfold) with a machine-learning approach (boctopus2)
      for predicting beta-strands in the barrel. In a blinded test for 19 TMB proteins
      of known structure that have a sufficient number of diverse homologous sequences
      available, this combined method (EVfold_bb) predicts hydrogen-bonded residue
      pairs between adjacent beta-strands at an accuracy of ~70%. This accuracy is
      sufficient for the generation of all-atom 3D models. In the transmembrane barrel
      region, the average 3D structure accuracy [template-modeling (TM) score] of top
      ranked models is 0.54 (ranging from 0.36 to 0.85), with a higher (44%) number of
      residue pairs in correct strand-strand registration than in earlier methods
      (18%). Although the nonbarrel regions are predicted less accurately overall, the
      evolutionary couplings identify some highly constrained loop residues and, for
      FecA protein, the barrel including the structure of a plug domain can be
      accurately modeled (TM score = 0.68). Lower prediction accuracy tends to be
      associated with insufficient sequence information and we therefore expect
      increasing numbers of beta-barrel families to become accessible to accurate 3D
      structure prediction as the number of available sequences increases. 

PMID- 25858952
TI  - New signaling pathways govern the host response to C. albicans infection in
      various niches.
AB  - Candida albicans, the major invasive fungal pathogen of humans, can cause both
      debilitating mucosal infections and fatal invasive infections. Understanding the
      complex nature of the host-pathogen interaction in each of these contexts is
      essential to developing desperately needed therapies to treat fungal infections.
      RNA-seq enables a systems-level understanding of infection by facilitating
      comprehensive analysis of transcriptomes from multiple species (e.g., host and
      pathogen) simultaneously. We used RNA-seq to characterize the transcriptomes of
      both C. albicans and human endothelial cells or oral epithelial cells during in
      vitro infection. Network analysis of the differentially expressed genes
      identified the activation of several signaling pathways that have not previously
      been associated with the host response to fungal pathogens. Using an siRNA
      knockdown approach, we demonstrate that two of these pathways-platelet-derived
      growth factor BB (PDGF BB) and neural precursor-cell-expressed developmentally
      down-regulated protein 9 (NEDD9)-govern the host-pathogen interaction by
      regulating the uptake of C. albicans by host cells. Using RNA-seq analysis of a
      mouse model of hematogenously disseminated candidiasis (HDC) and episodes of
      vulvovaginal candidiasis (VVC) in humans, we found evidence that many of the same
      signaling pathways are activated during mucosal (VVC) and/or disseminated (HDC)
      infections in vivo. Our analyses have uncovered several signaling pathways at the
      interface between C. albicans and host cells in various contexts of infection,
      and suggest that PDGF BB and NEDD9 play important roles in this interaction. In
      addition, these data provide a valuable community resource for better
      understanding host-fungal pathogen interactions.

PMID- 25858954
TI  - Singlet fission in pentacene dimers.
AB  - Singlet fission (SF) has the potential to supersede the traditional solar energy
      conversion scheme by means of boosting the photon-to-current conversion
      efficiencies beyond the 30% Shockley-Queisser limit. Here, we show unambiguous
      and compelling evidence for unprecedented intramolecular SF within regioisomeric
      pentacene dimers in room-temperature solutions, with observed triplet quantum
      yields reaching as high as 156 +/- 5%. Whereas previous studies have shown that
      the collision of a photoexcited chromophore with a ground-state chromophore can
      give rise to SF, here we demonstrate that the proximity and sufficient coupling
      through bond or space in pentacene dimers is enough to induce intramolecular SF
      where two triplets are generated on one molecule. 

PMID- 25858955
TI  - Transcranial direct current stimulation to lateral prefrontal cortex could
      increase meta-awareness of mind wandering.

PMID- 25858956
TI  - The Diversity of Meningococcal Carriage Across the African Meningitis Belt and
      the Impact of Vaccination With a Group A Meningococcal Conjugate Vaccine.
AB  - BACKGROUND: Study of meningococcal carriage is essential to understanding the
      epidemiology of Neisseria meningitidis infection. METHODS: Twenty cross-sectional
      carriage surveys were conducted in 7 countries in the African meningitis belt; 5
      surveys were conducted after introduction of a new serogroup A meningococcal
      conjugate vaccine (MenAfriVac). Pharyngeal swab specimens were collected, and
      Neisseria species were identified by microbiological and molecular techniques.
      RESULTS: A total of 1687 of 48 490 participants (3.4%; 95% confidence interval
      [CI], 3.2%-3.6%) carried meningococci. Carriage was more frequent in individuals
      aged 5-14 years, relative to those aged 15-29 years (adjusted odds ratio [OR],
      1.41; 95% CI, 1.25-1.60); in males, relative to females (adjusted OR, 1.17; 95%
      CI, 1.10-1.24); in individuals in rural areas, relative to those in urban areas
      (adjusted OR, 1.44; 95% CI, 1.28-1.63); and in the dry season, relative to the
      rainy season (adjusted OR, 1.54; 95% CI, 1.37-1.75). Forty-eight percent of
      isolates had genes encoding disease-associated polysaccharide capsules; genogroup
      W predominated, and genogroup A was rare. Strain diversity was lower in countries
      in the center of the meningitis belt than in Senegal or Ethiopia. The prevalence
      of genogroup A fell from 0.7% to 0.02% in Chad following mass vaccination with
      MenAfriVac. CONCLUSIONS: The prevalence of meningococcal carriage in the African
      meningitis belt is lower than in industrialized countries and is very diverse and
      dynamic, even in the absence of vaccination.

PMID- 25858957
TI  - Antibody to Influenza Virus Neuraminidase: An Independent Correlate of
      Protection.
AB  - BACKGROUND: Laboratory correlates of influenza vaccine protection can best be
      identified by examining people who are infected despite vaccination. While the
      importance of antibody to viral hemagglutinin (HA) has long been recognized, the
      level of protection contributed independently by antibody to viral neuraminidase
      (NA) has not been determined. METHODS: Sera from a controlled trial of the
      efficacies of inactivated influenza vaccine (IIV) and live attenuated influenza
      vaccine (LAIV) were tested by hemagglutination inhibition (HAI) assay,
      microneutralization (MN) assay, and a newly standardized lectin-based
      neuraminidase inhibition (NAI) assay. RESULTS: The NAI assay detected a vaccine
      response in 37% of IIV recipients, compared with 77% and 67% of participants in
      whom responses were detected by the HAI and MN assays, respectively. For LAIV
      recipients, the NAI, HAI, and MN assays detected responses in 6%, 21%, and 17%,
      respectively. In IIV recipients, as NAI assay titers rose, the frequency of
      infection fell, similar to patterns seen with HAI and MN assays. HAI and MN assay
      titers were highly correlated, but NAI assay titers exhibited less of a
      correlation. Analyses suggested an independent role for NAI antibody in
      protection, which was similar in the IIV, LAIV, and placebo groups. CONCLUSIONS:
      While NAI antibody is not produced to a large extent in response to current IIV,
      it appears to have an independent role in protection. As new influenza vaccines
      are developed, NA content should be considered. CLINICAL TRIALS REGISTRATION:
      NCT00538512.

PMID- 25858958
TI  - Neuraminidase: Another Piece of the Influenza Vaccine Puzzle.

PMID- 25858959
TI  - Long-Read Single Molecule Sequencing to Resolve Tandem Gene Copies: The Mst77Y
      Region on the Drosophila melanogaster Y Chromosome.
AB  - The autosomal gene Mst77F of Drosophila melanogaster is essential for male
      fertility. In 2010, Krsticevic et al. (Genetics 184: 295-307) found 18 Y-linked
      copies of Mst77F ("Mst77Y"), which collectively account for 20% of the functional
      Mst77F-like mRNA. The Mst77Y genes were severely misassembled in the then
      available genome assembly and were identified by cloning and sequencing
      polymerase chain reaction products. The genomic structure of the Mst77Y region
      and the possible existence of additional copies remained unknown. The recent
      publication of two long-read assemblies of D. melanogaster prompted us to
      reinvestigate this challenging region of the Y chromosome. We found that the
      Illumina Synthetic Long Reads assembly failed in the Mst77Y region, most likely
      because of its tandem duplication structure. The PacBio MHAP assembly of the
      Mst77Y region seems to be very accurate, as revealed by comparisons with the
      previously found Mst77Y genes, a bacterial artificial chromosome sequence, and
      Illumina reads of the same strain. We found that the Mst77Y region spans 96 kb
      and originated from a 3.4-kb transposition from chromosome 3L to the Y
      chromosome, followed by tandem duplications inside the Y chromosome and invasion
      of transposable elements, which account for 48% of its length. Twelve of the 18
      Mst77Y genes found in 2010 were confirmed in the PacBio assembly, the remaining
      six being polymerase chain reaction-induced artifacts. There are several
      identical copies of some Mst77Y genes, coincidentally bringing the total copy
      number to 18. Besides providing a detailed picture of the Mst77Y region, our
      results highlight the utility of PacBio technology in assembling difficult
      genomic regions such as tandemly repeated genes. 

PMID- 25858961
TI  - Correction.

PMID- 25858960
TI  - BAC-End Sequence-Based SNP Mining in Allotetraploid Cotton (Gossypium) Utilizing
      Resequencing Data, Phylogenetic Inferences, and Perspectives for Genetic Mapping.
AB  - A bacterial artificial chromosome library and BAC-end sequences for cultivated
      cotton (Gossypium hirsutum L.) have recently been developed. This report presents
      genome-wide single nucleotide polymorphism (SNP) mining utilizing resequencing
      data with BAC-end sequences as a reference by alignment of 12 G. hirsutum L.
      lines, one G. barbadense L. line, and one G. longicalyx Hutch and Lee line. A
      total of 132,262 intraspecific SNPs have been developed for G. hirsutum, whereas
      223,138 and 470,631 interspecific SNPs have been developed for G. barbadense and
      G. longicalyx, respectively. Using a set of interspecific SNPs, 11 randomly
      selected and 77 SNPs that are putatively associated with the homeologous
      chromosome pair 12 and 26, we mapped 77 SNPs into two linkage groups representing
      these chromosomes, spanning a total of 236.2 cM in an interspecific F2 population
      (G. barbadense 3-79 * G. hirsutum TM-1). The mapping results validated the
      approach for reliably producing large numbers of both intraspecific and
      interspecific SNPs aligned to BAC-ends. This will allow for future construction
      of high-density integrated physical and genetic maps for cotton and other complex
      polyploid genomes. The methods developed will allow for future Gossypium
      resequencing data to be automatically genotyped for identified SNPs along the BAC
      end sequence reference for anchoring sequence assemblies and comparative studies.

PMID- 25858963
TI  - Correction.

PMID- 25858962
TI  - Hemiballism with leg predominance caused by contralateral subthalamic
      haemorrhage.
AB  - Hemiballism is a rare movement disorder characterised by high-amplitude movements
      of the limbs on one side of the body. Stroke of the contralateral basal ganglia,
      especially the subthalamic nucleus (STN) is the most common aetiology of acute
      development of hemiballism. Recently, the pathophysiology of hemiballism has been
      associated with abnormal firing patterns in the globus pallidus interna, with
      intermittent firing bursts followed by pauses, during which movements occur. An
      87-year-old woman presented with a 5-day history of hemiballism predominantly in
      her leg. On the basis of her brain MRI findings, she was diagnosed as having
      vascular hemiballism caused by haemorrhage in the contralateral STN. Treatment
      with risperidone led to the clinical resolution of her condition. We discuss the
      distribution of the patient's ballistic movements on the basis of the somatotopic
      organisation of the STN. 

PMID- 25858964
TI  - Ancestral amino acid substitution improves the thermal stability of recombinant
      lignin-peroxidase from white-rot fungi, Phanerochaete chrysosporium strain UAMH
      3641.
AB  - Stabilizing enzymes from mesophiles of industrial interest is one of the greatest
      challenges of protein engineering. The ancestral mutation method, which
      introduces inferred ancestral residues into a target enzyme, has previously been
      developed and used to improve the thermostability of thermophilic enzymes. In
      this report, we studied the ancestral mutation method to improve the chemical and
      thermal stabilities of Phanerochaete chrysosporium lignin peroxidase (LiP), a
      mesophilic fungal enzyme. A fungal ancestral LiP sequence was inferred using a
      phylogenetic tree comprising Basidiomycota and Ascomycota fungal peroxidase
      sequences. Eleven mutant enzymes containing ancestral residues were designed,
      heterologously expressed in Escherichia coli and purified. Several of these
      ancestral mutants showed higher thermal stabilities and increased specific
      activities and/or kcat/KM than those of wild-type LiP. 

PMID- 25858965
TI  - Political repression, civil society and the politics of responding to AIDS in the
      BRICS nations.
AB  - The policy responses to human immunodeficiency virus/acquired immune deficiency
      syndrome (AIDS) in the Brazil, Russia, India, China and South Africa (BRICS)
      nations have played out amid radically different political environments that have
      shaped state-civil society relations in critical ways. In contrasting these
      different environments, this article offers the first comparison of the policy
      response to AIDS in the BRICS nations and seeks to understand the way in which
      political context matters for conditioning the response to a major epidemic.
      Using a comparative historical approach, we find that while collaborative state
      civil society relations have produced an aggressive response and successful
      outcomes in Brazil, democratic openness and state-civil society engagement has
      not necessarily correlated with an aggressive response or better outcomes in the
      other cases. Response to the epidemic has been worst by far in democratic South
      Africa, followed by Russia, where in the former, denialism and antagonistic state
      civil society relations fuelled a delayed response and proved extremely costly in
      terms of human lives. In Russia, a lack of civil societal opportunity for
      mobilization and non-governmental organization (NGO) growth, political
      centralization and the state's unwillingness to work with NGOs led to an
      ineffective government response. Top-down bureaucratic rule and a reluctance to
      fully engage civil society in democratic India substantially delayed the state's
      efforts to engage in a successful partnership with NGOs. Nevertheless, China has
      done surprisingly well, in spite of its repressive approach and narrow engagement
      with civil society. And in all cases, we find the relationship between state and
      civil society to be evolving over time in important ways. These findings suggest
      the need for more research on the links between democratic openness, political
      repression and policy responses to epidemics.

PMID- 25858966
TI  - Direct Reversible Kidney Injury in Familial Hemophagocytic Lymphohistiocytosis
      Type 3.
AB  - Hemophagocytic lymphohistiocytosis is a hyperinflammatory disorder resulting from
      primary or secondary immune dysfunction. AKI is frequent in severe hemophagocytic
      lymphohistiocytosis and has been attributed to multiorgan failure or the use of
      nephrotoxic drugs, but AKI is rarely considered a direct consequence of the
      disease process. We describe a child with familial hemophagocytic
      lymphohistiocytosis type 3 who developed AKI requiring prolonged renal
      replacement therapy because of severe renal inflammation. There was massive
      infiltration of the renal parenchyma by activated macrophages and cytotoxic T
      cells, and acute tubular injury. The patient responded to high-dose intravenous
      methylprednisolone, which resulted in improvement of renal function and
      discontinuation of renal replacement therapy. This case confirms the occurrence
      of reversible AKI due to hemophagocytic lymphohistiocytosis-induced activated
      macrophage infiltration of the renal parenchyma and inflammation.

PMID- 25858968
TI  - The Neural Signature of Subliminal Visuomotor Priming: Brain Activity and
      Functional Connectivity Profiles.
AB  - Unconscious visuomotor priming defined as the advantage in reaction time (RT) or
      accuracy for target shapes mapped to the same (congruent condition) when compared
      with a different (incongruent condition) motor response as a preceding
      subliminally presented prime shape has been shown to modulate activity within a
      visuomotor network comprised of parietal and frontal motor areas in previous
      functional magnetic resonance imaging (fMRI) studies. The present fMRI study
      investigated whether, in addition to changes in brain activity, unconscious
      visuomotor priming results in a modulation of functional connectivity profiles.
      Activity associated with congruent compared with incongruent trials was lower in
      the bilateral inferior and medial superior frontal gyri, in the inferior parietal
      lobules, and in the right caudate nucleus and adjacent portions of the thalamus.
      Functional connectivity increased under congruent relative to incongruent
      conditions between ventral visual stream areas (e.g., calcarine, fusiform, and
      lingual gyri), the precentral gyrus, the supplementary motor area, posterior
      parietal areas, the inferior frontal gyrus, and the caudate nucleus. Our findings
      suggest that an increase in coupling between visuomotor regions, reflecting
      higher efficiency of processing, is an important neural mechanism underlying
      unconscious visuomotor priming, in addition to changes in the magnitude of
      activation.

PMID- 25858967
TI  - A Podocyte-Based Automated Screening Assay Identifies Protective Small Molecules.
AB  - Podocyte injury and loss mark an early step in the pathogenesis of various
      glomerular diseases, making these cells excellent targets for therapeutics.
      However, cell-based high-throughput screening assays for the rational development
      of podocyte-directed therapeutics are currently lacking. Here, we describe a
      novel high-content screening-based phenotypic assay that analyzes thousands of
      podocytes per assay condition in 96-well plates to quantitatively measure dose
      dependent changes in multiple cellular features. Our assay consistently produced
      a Z' value >0.44, making it suitable for compound screening. On screening with
      >2100 pharmacologically active agents, we identified 24 small molecules that
      protected podocytes against injury in vitro (1% hit rate). Among the identified
      hits, we confirmed an beta1-integrin agonist, pyrintegrin, as a podocyte
      protective agent. Treatment with pyrintegrin prevented damage-induced decreases
      in F-actin stress fibers, focal adhesions, and active beta1-integrin levels in
      cultured cells. In vivo, administration of pyrintegrin protected mice from LPS
      induced podocyte foot process effacement and proteinuria. Analysis of the murine
      glomeruli showed that LPS administration reduced the levels of active beta1
      integrin in the podocytes, which was prevented by cotreatment with pyrintegrin.
      In rats, pyrintegrin reduced peak proteinuria caused by puromycin aminonucleoside
      induced nephropathy. Our findings identify pyrintegrin as a potential therapeutic
      candidate and show the use of podocyte-based screening assays for identifying
      novel therapeutics for proteinuric kidney diseases. 

PMID- 25858969
TI  - Others' Sheer Presence Boosts Brain Activity in the Attention (But Not the
      Motivation) Network.
AB  - The sheer presence of another member of the same species affects performance,
      sometimes impeding it, sometimes enhancing it. For well-learned tasks, the effect
      is generally positive. This fundamental form of social influence, known as social
      facilitation, concerns human as well as nonhuman animals and affects many
      behaviors from food consumption to cognition. In psychology, this phenomenon has
      been known for over a century. Yet, its underlying mechanism (motivation or
      attention) remains debated, its relationship to stress unclear, and its neural
      substrates unknown. To address these issues, we investigated the behavioral,
      neuronal, and endocrinological markers of social facilitation in monkeys trained
      to touch images to obtain rewards. When another animal was present, performance
      was enhanced, but testing-induced stress (i.e., plasma cortisol elevation) was
      unchanged, as was metabolic activity in the brain motivation network. Rather,
      task-related activity in the (right) attention frontoparietal network
      encompassing the lateral prefrontal cortex, ventral premotor cortex, frontal eye
      field, and intraparietal sulcus was increased when another individual was present
      compared with when animals were tested alone. These results establish the very
      first link between the behavioral enhancement produced by the mere presence of a
      peer and an increase of metabolic activity in those brain structures underpinning
      attention.

PMID- 25858970
TI  - Robust and Rugged Stability-Indicating HPLC Method for the Determination of
      Plerixafor and Its Related Impurities in Drug Substances.
AB  - A novel, reversed-phase high-performance liquid chromatographic method was
      developed and validated for the determination of related substances in Plerixafor
      (PLX) drug substance. PLX is an immunostimulant used to mobilize hematopoietic
      stem cells in cancer patients. The method is efficient for estimation of all
      degradation and process-related impurities. The method was developed using the
      Phenomenex Luna L11 column using the gradient program with mobile phase A and
      mobile phase B, where mobile phase A consists of pH 2.0 1-heptanesulfonic acid
      sodium salt buffer and acetonitrile in the ratio of 80:20 (v/v) and mobile phase
      B consists of pH 2.0 1-heptanesulfonic acid sodium salt buffer and acetonitrile
      in the ratio of 20:80 (v/v). PLX and its impurities were monitored at 210 nm. The
      present work is describing the role of ion-pair reagent in the separation of
      polar compounds. PLX was subjected to various stress conditions of oxidative,
      acid, base, hydrolytic, thermal, humidity and photolytic degradations. The
      degradation products were well separated from each other and with the main peak,
      demonstrating the stability-indicating power of the method. The performance of
      the method was validated according to the present ICH guidelines for specificity,
      limit of detection, limit of quantification, linearity, accuracy, precision,
      ruggedness and robustness. 

PMID- 25858971
TI  - Toward Understanding Ambulatory Activity Decline in Parkinson Disease.
AB  - BACKGROUND: Declining ambulatory activity represents an important facet of
      disablement in Parkinson disease (PD). OBJECTIVE: The primary study aim was to
      compare the 2-year trajectory of ambulatory activity decline with concurrently
      evolving facets of disability in a small cohort of people with PD. The secondary
      aim was to identify baseline variables associated with ambulatory activity at 1-
      and 2-year follow-up assessments. DESIGN: This was a prospective, longitudinal
      cohort study. METHODS: Seventeen people with PD (Hoehn and Yahr stages 1-3) were
      recruited from 2 outpatient settings. Ambulatory activity data were collected at
      baseline and at 1- and 2-year annual assessments. Motor, mood, balance, gait,
      upper extremity function, quality of life, self-efficacy, and levodopa equivalent
      daily dose data and data on activities of daily living also were collected.
      RESULTS: Participants displayed significant 1- and 2-year declines in the amount
      and intensity of ambulatory activity concurrently with increasing levodopa
      equivalent daily dose. Worsening motor symptoms and slowing of gait were apparent
      only after 2 years. Concurrent changes in the remaining clinical variables were
      not observed. Baseline ambulatory activity and physical performance variables had
      the strongest relationships with 1- and 2-year mean daily steps. LIMITATIONS: The
      sample was small and homogeneous. CONCLUSIONS: Future research that combines
      ambulatory activity monitoring with a broader and more balanced array of measures
      would further illuminate the dynamic interactions among evolving facets of
      disablement and help determine the extent to which sustained patterns of
      recommended daily physical activity might slow the rate of disablement in PD.

PMID- 25858973
TI  - Relationship Between Skin Intrinsic Fluorescence--an Indicator of Advanced
      Glycation End Products-and Upper Extremity Impairments in Individuals With
      Diabetes Mellitus.
AB  - BACKGROUND: Accumulation of advanced glycation end products (AGEs) is thought to
      contribute to limited joint mobility in people with diabetes mellitus (DM), but
      the relationships among AGEs, shoulder structural changes, movement, and
      disability are not understood. OBJECTIVE: The purpose of this study was to
      determine the differences and relationships among skin intrinsic fluorescence
      (SIF), a proxy measure of AGEs, biceps and supraspinatus tendon thickness, upper
      extremity movement, and disability in groups with and without DM. DESIGN: This
      was a cross-sectional, case-control study. METHODS: Fifty-two individuals
      participated: 26 with type 2 DM and 26 controls matched for sex, age, and body
      mass index. The main outcome measures were: SIF; biceps and supraspinatus tendon
      thickness; 3-dimensional peak shoulder motion; and Disability of the Arm,
      Shoulder and Hand (DASH) questionnaire scores. RESULTS: Mean SIF measurements
      were 19% higher in the DM group compared with the control group (P<.05). Biceps
      tendons (mean and 95% confidence interval [CI]) (4.7 mm [4.4, 5.0] versus 3.2 mm
      [2.9, 3.5]) and supraspinatus tendons (6.4 mm [5.9, 6.8] versus 4.9 mm [4.4,
      5.3]) were thicker and peak humerothoracic elevation (139 degrees  [135 degrees ,
      146 degrees ] versus 150 degrees  [146 degrees , 155 degrees ]) and glenohumeral
      external rotation (35 degrees  [26 degrees , 46 degrees ] versus 51 degrees  [41
      degrees , 58 degrees ]) were reduced in the DM group compared with the control
      group (P<.05). In the DM group, SIF was correlated to biceps tendon thickness,
      DASH score, and shoulder motion (r=.44-.51, P<.05). The SIF score and shoulder
      strength explained 64% of the DASH scores (P<.01). LIMITATIONS: Because this was
      a cross-sectional study design, a cause-effect relationship could not be
      established. CONCLUSIONS: Accumulation of AGEs in the connective tissues of
      individuals with DM appears to be associated with increased tendon thickness and
      decreased shoulder joint mobility and upper extremity function. Physical
      therapists should be aware of these possible metabolic effects on structure,
      movement, and disability when treating people with diabetes.

PMID- 25858974
TI  - Efficacy of a Novel Method for Inspiratory Muscle Training in People With Chronic
      Obstructive Pulmonary Disease.
AB  - BACKGROUND: Most inspiratory muscle training (IMT) interventions in patients with
      chronic obstructive pulmonary disease (COPD) have been implemented as fully
      supervised daily training for 30 minutes with controlled training loads using
      mechanical threshold loading (MTL) devices. Recently, an electronic tapered flow
      resistive loading (TFRL) device was introduced that has a different loading
      profile and stores training data during IMT sessions. OBJECTIVE: The aim of this
      study was to compare the efficacy of a brief, largely unsupervised IMT protocol
      conducted using either traditional MTL or TFRL on inspiratory muscle function in
      patients with COPD. DESIGN: Twenty patients with inspiratory muscle weakness who
      were clinically stable and participating in a pulmonary rehabilitation program
      were randomly allocated to perform 8 weeks of either MTL IMT or TFRL IMT.
      METHODS: Participants performed 2 daily home-based IMT sessions of 30 breaths (3
      5 minutes per session) at the highest tolerable intensity, supported by twice
      weekly supervised sessions. Adherence, progression of training intensity,
      increases in maximal inspiratory mouth pressure (Pimax), and endurance capacity
      of inspiratory muscles (Tlim) were evaluated. RESULTS: More than 90% of IMT
      sessions were completed in both groups. The TFRL group tolerated higher loads
      during the final 3 weeks of the IMT program, with similar effort scores on the 10
      Item Borg Category Ratio (CR-10) Scale, and achieved larger improvements in Pimax
      and Tlim than the MTL group. LIMITATIONS: A limitation of the study was the
      absence of a study arm involving a sham IMT intervention. CONCLUSIONS: The short
      and largely home-based IMT protocol significantly improved inspiratory muscle
      function in both groups and is an alternative to traditional IMT protocols in
      this population. Participants in the TFRL group tolerated higher training loads
      and achieved larger improvements in inspiratory muscle function than those in the
      MTL group.

PMID- 25858972
TI  - Pragmatic Implementation of a Stratified Primary Care Model for Low Back Pain
      Management in Outpatient Physical Therapy Settings: Two-Phase, Sequential
      Preliminary Study.
AB  - BACKGROUND: The effectiveness of risk stratification for low back pain (LBP)
      management has not been demonstrated in outpatient physical therapy settings.
      OBJECTIVE: The purposes of this study were: (1) to assess implementation of a
      stratified care approach for LBP management by evaluating short-term treatment
      effects and (2) to determine feasibility of conducting a larger-scale study.
      DESIGN: This was a 2-phase, preliminary study. METHODS: In phase 1, clinicians
      were randomly assigned to receive standard (n=6) or stratified care (n=6)
      training. Stratified care training included 8 hours of content focusing on
      psychologically informed practice. Changes in LBP attitudes and beliefs were
      assessed using the Pain Attitudes and Beliefs Scale for Physiotherapists (PABS
      PT) and the Health Care Providers Pain and Impairment Relationship Scale (HC
      PAIRS). In phase 2, clinicians receiving the stratified care training were
      instructed to incorporate those strategies in their practice and 4-week patient
      outcomes were collected using a numerical pain rating scale (NPRS), and the
      Oswestry Disability Index (ODI). Study feasibility was assessed to identify
      potential barriers for completion of a larger-scale study. RESULTS: In phase 1,
      minimal changes were observed for PABS-PT and HC-PAIRS scores for standard care
      clinicians (Cohen d=0.00-0.28). Decreased biomedical (-4.5+/-2.5 points, d=1.08)
      and increased biopsychosocial (+5.5+/-2.0 points, d=2.86) treatment orientations
      were observed for stratified care clinicians, with these changes sustained 6
      months later on the PABS-PT. In phase 2, patients receiving stratified care
      (n=67) had greater between-group improvements in NPRS (0.8 points; 95% confidence
      interval=0.1, 1.5; d=0.40) and ODI (8.9% points; 95% confidence interval=4.1,
      13.6; d=0.76) scores compared with patients receiving standard physical therapy
      care (n=33). LIMITATIONS: In phase 2, treatment was not randomly assigned, and
      therapist adherence to treatment recommendations was not monitored. This study
      was not adequately powered to conduct subgroup analyses. CONCLUSIONS: In physical
      therapy settings, biomedical orientation can be modified, and risk-stratified
      care for LBP can be effectively implemented. Findings from this study can be used
      for planning of larger studies.

PMID- 25858975
TI  - Safety and efficacy of resolute zotarolimus-eluting stents compared with
      everolimus-eluting stents: a meta-analysis.
AB  - BACKGROUND: Although new-generation drug-eluting stents represent the standard of
      care among patients undergoing percutaneous coronary intervention, there remains
      debate about differences in efficacy and the risk of stent thrombosis between the
      Resolute zotarolimus-eluting stent (R-ZES) and the everolimus-eluting stent
      (EES). The aim of this study was to evaluate the safety and efficacy of the R-ZES
      compared with EES in patients undergoing percutaneous coronary intervention.
      METHODS AND RESULTS: A systematic literature search of electronic resources was
      performed using specific search terms until September 2014. Random-effects meta
      analysis was performed comparing clinical outcomes between patients treated with
      R-ZES and EES up to maximum available follow-up. The primary efficacy end point
      was target-vessel revascularization. The primary safety end point was definite or
      probable stent thrombosis. Secondary safety end points were cardiac death and
      target-vessel myocardial infarction. Five trials were identified, including a
      total of 9899 patients. Compared with EES, R-ZES had similar risks of target
      vessel revascularization (risk ratio [RR], 1.06; 95% confidence interval [CI],
      0.90-1.24; P=0.50), definite or probable stent thrombosis (RR, 1.26; 95% CI, 0.86
      1.85; P=0.24), cardiac death (RR, 1.01; 95% CI, 0.79-1.30; P=0.91), and target
      vessel myocardial infarction (RR, 1.10; 95% CI, 0.89-1.36; P=0.39). Moreover, R
      ZES and EES had similar risks of late definite or probable very late stent
      thrombosis (RR, 1.06; 95% CI, 0.53-2.11; P=0.87). No evidence of significant
      heterogeneity was observed across trials. CONCLUSIONS: R-ZES and EES provide
      similar safety and efficacy among patients undergoing percutaneous coronary
      intervention.

PMID- 25858976
TI  - Cerebrovascular events after a primary percutaneous coronary intervention
      strategy for acute ST-segment-elevation myocardial infarction: analysis from the
      HORIZONS-AMI Trial.
AB  - BACKGROUND: Patients with ST-segment-elevation myocardial infarction are at
      increased risk of cerebrovascular events. We assessed the incidence, predictors,
      and implications of cerebrovascular events in patients with ST-segment-elevation
      myocardial infarction managed with a primary percutaneous coronary intervention
      strategy. METHODS AND RESULTS: In the Harmonizing Outcomes With Revascularization
      and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial, 72 of 3602
      patients (2.0%) experienced at least 1 cerebrovascular event (stroke: 63
      patients; transient ischemic attack: 12 patients) during the 3-year follow-up
      (40.3% within 30 days, 20.8% between 30 days and 1 year, and 38.9% between 1 and
      3 years). Stroke was ischemic in 58 (92.1%) patients and hemorrhagic in 5 (7.9%)
      patients. More than half of all strokes (52.3%) were disabling. By principal
      management strategy, cerebrovascular events developed in 2.0%, 14.9%, and 1.9% of
      patients triaged to primary percutaneous coronary intervention, coronary artery
      bypass grafting, and medical therapy, respectively (P<0.0001). Cerebrovascular
      events were independently predicted by older age, creatinine clearance <60
      mL/min, treatment with coronary artery bypass grafting, anemia, and diabetes
      mellitus. Cerebrovascular events were associated with significantly increased
      rates of 3-year mortality (20.5% versus 6.5%; P<0.0001), as well as reinfarction
      (14.3% versus 3.8%; P=0.0007), ischemia-driven target vessel revascularization
      (22.8% versus 13.0%; P=0.006), and major bleeding (23.5% versus 8.4%; P<0.0001).
      CONCLUSIONS: In HORIZONS-AMI, cerebrovascular events within 3 years after ST
      segment-elevation myocardial infarction in patients undergoing a primary
      percutaneous coronary intervention management strategy occurred in 2.0% of
      patients and were most frequent after coronary artery bypass grafting.
      Cerebrovascular events were often disabling and were strongly associated with
      high rates of death, reinfarction, recurrent ischemia, and major bleeding.
      CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique
      identifier: NCT00433966.

PMID- 25858977
TI  - RNA imaging. Spatially resolved, highly multiplexed RNA profiling in single
      cells.
AB  - Knowledge of the expression profile and spatial landscape of the transcriptome in
      individual cells is essential for understanding the rich repertoire of cellular
      behaviors. Here, we report multiplexed error-robust fluorescence in situ
      hybridization (MERFISH), a single-molecule imaging approach that allows the copy
      numbers and spatial localizations of thousands of RNA species to be determined in
      single cells. Using error-robust encoding schemes to combat single-molecule
      labeling and detection errors, we demonstrated the imaging of 100 to 1000
      distinct RNA species in hundreds of individual cells. Correlation analysis of the
      ~10(4) to 10(6) pairs of genes allowed us to constrain gene regulatory networks,
      predict novel functions for many unannotated genes, and identify distinct spatial
      distribution patterns of RNAs that correlate with properties of the encoded
      proteins. 

PMID- 25858978
TI  - Catalysis. Identification of molybdenum oxide nanostructures on zeolites for
      natural gas conversion.
AB  - Direct methane conversion into aromatic hydrocarbons over catalysts with
      molybdenum (Mo) nanostructures supported on shape-selective zeolites is a
      promising technology for natural gas liquefaction. We determined the identity and
      anchoring sites of the initial Mo structures in such catalysts as isolated oxide
      species with a single Mo atom on aluminum sites in the zeolite framework and on
      silicon sites on the zeolite external surface. During the reaction, the initial
      isolated Mo oxide species agglomerate and convert into carbided Mo nanoparticles.
      This process is reversible, and the initial isolated Mo oxide species can be
      restored by a treatment with gas-phase oxygen. Furthermore, the distribution of
      the Mo nanostructures can be controlled and catalytic performance can be fully
      restored, even enhanced, by adjusting the oxygen treatment. 

PMID- 25858981
TI  - Call for harmonised legislation on cats and dogs.

PMID- 25858982
TI  - Welsh dog breeders reminded of impending rule changes.

PMID- 25858979
TI  - Stress responses. Mutations in a translation initiation factor identify the
      target of a memory-enhancing compound.
AB  - The integrated stress response (ISR) modulates messenger RNA translation to
      regulate the mammalian unfolded protein response (UPR), immunity, and memory
      formation. A chemical ISR inhibitor, ISRIB, enhances cognitive function and
      modulates the UPR in vivo. To explore mechanisms involved in ISRIB action, we
      screened cultured mammalian cells for somatic mutations that reversed its effect
      on the ISR. Clustered missense mutations were found at the amino-terminal portion
      of the delta subunit of guanine nucleotide exchange factor (GEF) eIF2B. When
      reintroduced by CRISPR-Cas9 gene editing of wild-type cells, these mutations
      reversed both ISRIB-mediated inhibition of the ISR and its stimulatory effect on
      eIF2B GEF activity toward its substrate, the translation initiation factor eIF2,
      in vitro. Thus, ISRIB targets an interaction between eIF2 and eIF2B that lies at
      the core of the ISR. 

PMID- 25858983
TI  - Scotland's food body starts work.

PMID- 25858984
TI  - Pet nutrition: animation explains how pet food is made.

PMID- 25858988
TI  - One Health: more than just collaboration.
AB  - One Health has become a hot topic in recent years, and the impetus does not seem
      to be waning. But what is One Health? Is it simply the collaboration of human and
      veterinary medicine, or is it something bigger? And how can the veterinary and
      medical professions best embrace it? These questions were discussed at a
      conference organised by the Veterinary Public Health Association (VPHA) and
      Association of Government Veterinarians (AGV) on March 21. Georgina Mills
      reports. 

PMID- 25858989
TI  - US government sets out action plan for addressing antimicrobial resistance.

PMID- 25858990
TI  - Funding for cattle data exchange system.

PMID- 25858992
TI  - Bronchointerstitial pneumonia in Scottish cattle.

PMID- 25858993
TI  - 'New Forest syndrome': first pieces of the puzzle.

PMID- 25858994
TI  - Correction. Antibiotic susceptibility of bacterial isolates from 502 dogs with
      respiratory signs (VR, April 4, 2015, vol 176, p 357; doi: 10.1136/vr.102694).

PMID- 25858995
TI  - CRGV in dogs visiting the New Forest.

PMID- 25858996
TI  - CRGV in dogs visiting the New Forest.

PMID- 25858997
TI  - TB testing.

PMID- 25858998
TI  - Misconceptions regarding rabbit behaviour.

PMID- 25858999
TI  - Diagnostic test for ovine chlamydiosis.

PMID- 25859000
TI  - Factors to consider when prescribing antibiotics.

PMID- 25859001
TI  - Pig welfare app.

PMID- 25859002
TI  - Preventing parasites inside and out.

PMID- 25859003
TI  - Online guides to positioning dogs for radiography.

PMID- 25859004
TI  - Learning down under.

PMID- 25859005
TI  - First-year student diary.

PMID- 25859006
TI  - Antioxidant and anti-inflammatory agents mitigate pathology in a mouse model of
      pseudoachondroplasia.
AB  - Pseudoachondroplasia (PSACH), a severe short-limb dwarfing condition, results
      from mutations that cause misfolding of the cartilage oligomeric matrix protein
      (COMP). Accumulated COMP in growth plate chondrocytes activates endoplasmic
      reticulum stress, leading to inflammation and chondrocyte death. Using a MT-COMP
      mouse model of PSACH that recapitulates the molecular and clinical PSACH
      phenotype, we previously reported that oxidative stress and inflammation play
      important and unappreciated roles in PSACH pathology. In this study, we assessed
      the ability of antioxidant and anti-inflammatory agents to affect skeletal and
      cellular pathology in our mouse model of PSACH. Treatment of MT-COMP mice with
      aspirin or resveratrol from birth to P28 decreased mutant COMP intracellular
      retention and chondrocyte cell death, and restored chondrocyte proliferation.
      Inflammatory markers associated with cartilage degradation and eosinophils were
      present in the joints of untreated juvenile MT-COMP mice, but were undetectable
      in treated mice. Most importantly, these treatments resulted in significantly
      increased femur length. This is the first and only therapeutic approach shown to
      mitigate both the chondrocyte and long-bone pathology of PSACH in a mouse model
      and suggests that reducing inflammation and oxidative stress early in the disease
      process may be a novel approach to treat this disorder. 

PMID- 25859007
TI  - CEP290 alleles in mice disrupt tissue-specific cilia biogenesis and recapitulate
      features of syndromic ciliopathies.
AB  - Distinct mutations in the centrosomal-cilia protein CEP290 lead to diverse
      clinical findings in syndromic ciliopathies. We show that CEP290 localizes to the
      transition zone in ciliated cells, precisely to the region of Y-linkers between
      central microtubules and plasma membrane. To create models of CEP290-associated
      ciliopathy syndromes, we generated Cep290(ko/ko) and Cep290(gt/gt) mice that
      produce no or a truncated CEP290 protein, respectively. Cep290(ko/ko) mice
      exhibit early vision loss and die from hydrocephalus. Retinal photoreceptors in
      Cep290(ko/ko) mice lack connecting cilia, and ciliated ventricular ependyma fails
      to mature. The minority of Cep290(ko/ko) mice that escape hydrocephalus
      demonstrate progressive kidney pathology. Cep290(gt/gt) mice die at mid
      gestation, and the occasional Cep290(gt/gt) mouse that survives shows
      hydrocephalus and severely cystic kidneys. Partial loss of CEP290-interacting
      ciliopathy protein MKKS mitigates lethality and renal pathology in Cep290(gt/gt)
      mice. Our studies demonstrate domain-specific functions of CEP290 and provide
      novel therapeutic paradigms for ciliopathies. 

PMID- 25859008
TI  - Proteolytic cleavage of ataxin-7 promotes SCA7 retinal degeneration and
      neurological dysfunction.
AB  - The neurodegenerative disorder spinocerebellar ataxia type 7 (SCA7) is caused by
      a polyglutamine (polyQ) expansion in the ataxin-7 protein, categorizing SCA7 as
      one member of a large class of heritable neurodegenerative proteinopathies.
      Cleavage of ataxin-7 by the protease caspase-7 has been demonstrated in vitro,
      and the accumulation of proteolytic cleavage products in SCA7 patients and mouse
      models has been identified as an early pathological change. However, it remains
      unknown whether a causal relationship exists between ataxin-7 proteolysis and in
      vivo SCA7 disease progression. To determine whether caspase cleavage is a
      critical event in SCA7 disease pathogenesis, we generated transgenic mice
      expressing polyQ-expanded ataxin-7 with a second-site mutation (D266N) to prevent
      caspase-7 proteolysis. When we compared SCA7-D266N mice with SCA7 mice lacking
      the D266N mutation, we found that SCA7-D266N mice exhibited improved motor
      performance, reduced neurodegeneration and substantial lifespan extension. Our
      findings indicate that proteolysis at the D266 caspase-7 cleavage site is an
      important mediator of ataxin-7 neurotoxicity, suggesting that inhibition of
      caspase-7 cleavage of polyQ-ataxin-7 may be a promising therapeutic strategy for
      this untreatable disorder. 

PMID- 25859009
TI  - SMN deficiency disrupts gastrointestinal and enteric nervous system function in
      mice.
AB  - The 2007 Consensus Statement for Standard of Care in Spinal Muscular Atrophy
      (SMA) notes that patients suffer from gastroesophageal reflux, constipation and
      delayed gastric emptying. We used two mouse models of SMA to determine whether
      functional GI complications are a direct consequence of or are secondary to
      survival motor neuron (Smn) deficiency. Our results show that despite normal
      activity levels and food and water intake, Smn deficiency caused constipation,
      delayed gastric emptying, slow intestinal transit and reduced colonic motility
      without gross anatomical or histopathological abnormalities. These changes
      indicate alterations to the intrinsic neural control of gut functions mediated by
      the enteric nervous system (ENS). Indeed, Smn deficiency led to disrupted ENS
      signaling to the smooth muscle of the colon but did not cause enteric neuron
      loss. High-frequency electrical field stimulation (EFS) of distal colon segments
      produced up to a 10-fold greater contractile response in Smn deficient tissues.
      EFS responses were not corrected by the addition of a neuronal nitric oxide
      synthase inhibitor indicating that the increased contractility was due to
      hyperexcitability and not disinhibition of the circuitry. The GI symptoms
      observed in mice are similar to those reported in SMA patients. Together these
      data suggest that ENS cells are susceptible to Smn deficiency and may underlie
      the patient GI symptoms. 

PMID- 25859010
TI  - Non-syndromic retinitis pigmentosa due to mutations in the mucopolysaccharidosis
      type IIIC gene, heparan-alpha-glucosaminide N-acetyltransferase (HGSNAT).
AB  - Retinitis pigmentosa (RP), the most common form of inherited retinal
      degeneration, is clinically and genetically heterogeneous and can appear as
      syndromic or non-syndromic. Mucopolysaccharidosis type IIIC (MPS IIIC) is a
      lethal disorder, caused by mutations in the heparan-alpha-glucosaminide N
      acetyltransferase (HGSNAT) gene and characterized by progressive neurological
      deterioration, with retinal degeneration as a prominent feature. We identified
      HGSNAT mutations in six patients with non-syndromic RP. Whole exome sequencing
      (WES) in an Ashkenazi Jewish Israeli RP patient revealed a novel homozygous
      HGSNAT variant, c.370A>T, which leads to partial skipping of exon 3. Screening of
      66 Ashkenazi RP index cases revealed an additional family with two siblings
      homozygous for c.370A>T. WES in three Dutch siblings with RP revealed a complex
      HGSNAT variant, c.[398G>C; 1843G>A] on one allele, and c.1843G>A on the other
      allele. HGSNAT activity levels in blood leukocytes of patients were reduced
      compared with healthy controls, but usually higher than those in MPS IIIC
      patients. All patients were diagnosed with non-syndromic RP and did not exhibit
      neurological deterioration, or any phenotypic features consistent with MPS IIIC.
      Furthermore, four of the patients were over 60 years old, exceeding by far the
      life expectancy of MPS IIIC patients. HGSNAT is highly expressed in the mouse
      retina, and we hypothesize that the retina requires higher HGSNAT activity to
      maintain proper function, compared with other tissues associated with MPS IIIC,
      such as the brain. This report broadens the spectrum of phenotypes associated
      with HGSNAT mutations and highlights the critical function of HGSNAT in the human
      retina. 

PMID- 25859012
TI  - Functional disruption of the dystrophin gene in rhesus monkey using CRISPR/Cas9.
AB  - CRISPR/Cas9 has been used to genetically modify genomes in a variety of species,
      including non-human primates. Unfortunately, this new technology does cause
      mosaic mutations, and we do not yet know whether such mutations can functionally
      disrupt the targeted gene or cause the pathology seen in human disease.
      Addressing these issues is necessary if we are to generate large animal models of
      human diseases using CRISPR/Cas9. Here we used CRISPR/Cas9 to target the monkey
      dystrophin gene to create mutations that lead to Duchenne muscular dystrophy
      (DMD), a recessive X-linked form of muscular dystrophy. Examination of the
      relative targeting rate revealed that Crispr/Cas9 targeting could lead to mosaic
      mutations in up to 87% of the dystrophin alleles in monkey muscle. Moreover,
      CRISPR/Cas9 induced mutations in both male and female monkeys, with the markedly
      depleted dystrophin and muscle degeneration seen in early DMD. Our findings
      indicate that CRISPR/Cas9 can efficiently generate monkey models of human
      diseases, regardless of inheritance patterns. The presence of degenerated muscle
      cells in newborn Cas9-targeted monkeys suggests that therapeutic interventions at
      the early disease stage may be effective at alleviating the myopathy. 

PMID- 25859014
TI  - Coronary artery bypass grafting and percutaneous coronary intervention in
      patients with end-stage renal disease.
AB  - OBJECTIVES: To determine the relative risks of long-term mortality between
      coronary artery bypass grafting (CABG) and percutaneous coronary intervention
      (PCI) among patients with end-stage renal disease (ESRD). METHODS: We identified
      1015 patients with ESRD who underwent coronary revascularization between 1996 and
      2008 within Kaiser Permanente Northern California. We obtained clinical variables
      from health plan databases, state death certificates and social security
      administration files. Our primary and secondary outcomes, respectively, were all
      cause mortality and repeat revascularization. Our primary predictor was CABG
      compared with PCI. We used a Cox proportional hazards model for multivariable
      analyses. RESULTS: The mean age of CABG and PCI patients was similar (64.7 +/-
      10.6 and 63.4 +/- 9.3, respectively, P = 0.06). The CABG group had a higher
      proportion of diabetics (P = 0.045), and higher nitrate use (P = 0.01). Adjusted
      for age, gender, race, year of index revascularization, number of vessels
      intervened, duration of dialysis and baseline comorbidities, patients referred
      for CABG during the first year had a hazard ratio (HR) of 1.16 [95% confidence
      interval (CI), 0.80-1.67] for mortality compared with PCI. During Years 1-5, the
      HR was 0.91 (95% CI, 0.63-1.33) with an overall HR of 0.73 (95% CI, 0.43-1.22).
      The sub-HR as calculated by the Fine-Gray competing risk model was 0.51 (95% CI,
      0.31-0.85). CONCLUSIONS: As there are no randomized clinical trials in this area,
      our observational study adds to the growing body of literature that suggests a
      significant decrease in repeat revascularization with CABG and at least
      equivalency in long-term mortality with CABG when compared with PCI in ESRD
      patients.

PMID- 25859011
TI  - Activation of non-myogenic mesenchymal stem cells during the disease progression
      in dystrophic dystrophin/utrophin knockout mice.
AB  - Ectopic calcification as well as fatty and fibrotic tissue accumulation occurs in
      skeletal muscle during the disease progression of Duchenne muscular dystrophy
      (DMD), a degenerative muscle disorder caused by mutations in the dystrophin gene.
      The cellular origin and the environmental cues responsible for this ectopic
      calcification, fatty and fibrotic infiltration during the disease progression,
      however, remain unknown. Based on a previously published preplate technique, we
      isolated two distinct populations of muscle-derived cells from skeletal muscle:
      (i) a rapidly adhering cell population, which is non-myogenic, Pax7(-) and
      express the mesenchymal stem cell (MSC) marker platelet-derived growth factor
      receptor alpha; hence, we termed this population of cells non-myogenic MSCs
      (nmMSCs); and (ii) a slowly adhering cell population which is Pax7(+) and highly
      myogenic, termed muscle progenitor cells (MPCs). Previously, we demonstrated that
      the rapid progression of skeletal muscle histopathologies in dystrophin/utrophin
      knockout (dys(-/-) utro(-/-) dKO) mice is closely associated with a rapid
      depletion of the MPC population pool. In the current study, we showed that in
      contrast to the MPCs, the nmMSCs become activated during the disease progression
      in dKO mice, displaying increased proliferation and differentiation potentials
      (adipogenesis, osteogenesis and fibrogenesis). We also found that after co
      culturing the dKO-nmMSCs with dKO-MPCs, the myogenic differentiation potential of
      the dKO-MPCs was reduced. This effect was found to be potentially mediated by the
      secretion of secreted frizzled-related protein 1 by the dKO-nmMSCs. We therefore
      posit that the rapid occurrence of fibrosis, ectopic calcification and fat
      accumulation, in dKO mice, is not only attributable to the rapid depletion of the
      MPC pool, but is also the consequence of nmMSC activation. Results from this
      study suggest that approaches to alleviate muscle weakness and wasting in DMD
      patients should not only target the myogenic MPCs but should also attempt to
      prevent the activation of the nmMSCs. 

PMID- 25859013
TI  - Defects in optineurin- and myosin VI-mediated cellular trafficking in amyotrophic
      lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder
      primarily affecting motor neurons. Mutations in optineurin cause a small
      proportion of familial ALS cases, and wild-type (WT) optineurin is misfolded and
      forms inclusions in sporadic ALS patient motor neurons. However, it is unknown
      how optineurin mutation or misfolding leads to ALS. Optineurin acts an adaptor
      protein connecting the molecular motor myosin VI to secretory vesicles and
      autophagosomes. Here, we demonstrate that ALS-linked mutations p.Q398X and
      p.E478G disrupt the association of optineurin with myosin VI, leading to an
      abnormal diffuse cytoplasmic distribution, inhibition of secretory protein
      trafficking, endoplasmic reticulum (ER) stress and Golgi fragmentation in motor
      neuron-like NSC-34 cells. We also provide further insight into the role of
      optineurin as an autophagy receptor. WT optineurin associated with lysosomes and
      promoted autophagosome fusion to lysosomes in neuronal cells, implying that it
      mediates trafficking of lysosomes during autophagy in association with myosin VI.
      However, either expression of ALS mutant optineurin or small interfering RNA
      mediated knockdown of endogenous optineurin blocked lysosome fusion to
      autophagosomes, resulting in autophagosome accumulation. Together these results
      indicate that ALS-linked mutations in optineurin disrupt myosin VI-mediated
      intracellular trafficking processes. In addition, in control human patient
      tissues, optineurin displayed its normal vesicular localization, but in sporadic
      ALS patient tissues, vesicles were present in a significantly decreased
      proportion of motor neurons. Optineurin binding to myosin VI was also decreased
      in tissue lysates from sporadic ALS spinal cords. This study therefore links
      several previously described pathological mechanisms in ALS, including defects in
      autophagy, fragmentation of the Golgi and induction of ER stress, to disruption
      of optineurin function. These findings also indicate that optineurin-myosin VI
      dysfunction is a common feature of both sporadic and familial ALS. 

PMID- 25859015
TI  - Hybrid stenting therapy for dysphagia aortica with Rokitansky's diverticulum
      concomitant with thoracic aortic aneurysm.
AB  - An 87-year old man with a past medical history of a descending aortic aneurysm
      for 20 years presented with progressive dysphagia and aspiration pneumonia.
      Computed tomography angiography demonstrated the impending rupture of the
      thoracic aortic aneurysm (TAA) and endoscopic examinations revealed the extrinsic
      compression of the middle oesophagus with Rokitansky's diverticulum proximal to
      the compression area. He underwent urgent thoracic endovascular aortic aneurysm
      repair, followed by oesophageal stenting. The patient's symptoms immediately
      improved, and the postoperative period was uneventful. This report is the first
      to describe a hybrid stenting therapy for dysphagia aortica with Rokitansky's
      diverticulum concomitant with a TAA. 

PMID- 25859017
TI  - Switch to DDD mode in SafeR algorithm could be delayed in paroxysmal atrial
      fibrillation and simultaneous occurrence of complete atrioventricular block.

PMID- 25859016
TI  - A new twist to the emerging functions of ceramides in cancer: novel role for
      platelet acid sphingomyelinase in cancer metastasis.
AB  - It is now appreciated that sphingolipids constitute a rich class of bioactive
      molecules that include ceramide, sphingosine, and sphingosine 1-phosphate whose
      formation is controlled by a network of highly regulated enzymes (Hannun & Obeid,
      2008). Notably, several stress stimuli induce the production of ceramide, which,
      as a single entity, has been traditionally associated with apoptotic and growth
      suppressive functions. However, recent data clearly suggest that this simplistic
      formulation is no longer tenable.

PMID- 25859018
TI  - NIH research: think globally.

PMID- 25859020
TI  - Nuclear Weapons. Iran deal would transform its nuclear infrastructure.

PMID- 25859021
TI  - Geochemistry. Acid oceans cited in Earth's worst die-off.

PMID- 25859022
TI  - Scientific Publishing. U.S. agencies fall in line on public access.

PMID- 25859023
TI  - Paleontology. Bully for Brontosaurus!

PMID- 25859024
TI  - Conservation. Brazil roils waters with moves to protect aquatic life.

PMID- 25859025
TI  - Cancer Biology. Infectious cancer found in clams.

PMID- 25859026
TI  - Startup liftoff.

PMID- 25859027
TI  - Thinking inside the box.

PMID- 25859028
TI  - Medicine. Transatlantic lessons in regulation of mitochondrial replacement
      therapy.

PMID- 25859029
TI  - Development. Aneuploidy and mother's genes.

PMID- 25859030
TI  - Cell Biology. Finding nascent proteins the right home.

PMID- 25859031
TI  - Biochemistry. Details of destruction, one molecule at a time.

PMID- 25859032
TI  - Physics. Assembling a complex quantum ensemble.

PMID- 25859033
TI  - Geology. An early start for the Panama land bridge.

PMID- 25859034
TI  - Drug Development. Are trade secrets delaying biosimilars?

PMID- 25859035
TI  - Optics. A chaotic approach clears up imaging.

PMID- 25859036
TI  - A new privacy debate.

PMID- 25859037
TI  - Assessing data intrusion threats.

PMID- 25859038
TI  - Assessing data intrusion threats--response.

PMID- 25859039
TI  - Outside the Tower. Acting to build trust.

PMID- 25859040
TI  - The principle of antagonism ensures protein targeting specificity at the
      endoplasmic reticulum.
AB  - The sorting of proteins to the appropriate compartment is one of the most
      fundamental cellular processes. We found that in the model organism
      Caenorhabditis elegans, correct cotranslational endoplasmic reticulum (ER)
      transport required the suppressor activity of the nascent polypeptide-associated
      complex (NAC). NAC did not affect the accurate targeting of ribosomes to ER
      translocons mediated by the signal recognition particle (SRP) pathway but
      inhibited additional unspecific contacts between ribosomes and translocons by
      blocking their autonomous binding affinity. NAC depletion shortened the life span
      of Caenorhabditis elegans, caused global mistargeting of translating ribosomes to
      the ER, and provoked incorrect import of mitochondrial proteins into the ER
      lumen, resulting in a strong impairment of protein homeostasis in both
      compartments. Thus, the antagonistic targeting activity of NAC is important in
      vivo to preserve the robustness and specificity of cellular protein-sorting
      routes. 

PMID- 25859041
TI  - Experimental observation of a generalized Gibbs ensemble.
AB  - The description of the non-equilibrium dynamics of isolated quantum many-body
      systems within the framework of statistical mechanics is a fundamental open
      question. Conventional thermodynamical ensembles fail to describe the large class
      of systems that exhibit nontrivial conserved quantities, and generalized
      ensembles have been predicted to maximize entropy in these systems. We show
      experimentally that a degenerate one-dimensional Bose gas relaxes to a state that
      can be described by such a generalized ensemble. This is verified through a
      detailed study of correlation functions up to 10th order. The applicability of
      the generalized ensemble description for isolated quantum many-body systems
      points to a natural emergence of classical statistical properties from the
      microscopic unitary quantum evolution. 

PMID- 25859042
TI  - Middle Miocene closure of the Central American Seaway.
AB  - Uranium-lead geochronology in detrital zircons and provenance analyses in eight
      boreholes and two surface stratigraphic sections in the northern Andes provide
      insight into the time of closure of the Central American Seaway. The timing of
      this closure has been correlated with Plio-Pleistocene global oceanographic,
      atmospheric, and biotic events. We found that a uniquely Panamanian Eocene
      detrital zircon fingerprint is pronounced in middle Miocene fluvial and shallow
      marine strata cropping out in the northern Andes but is absent in underlying
      lower Miocene and Oligocene strata. We contend that this fingerprint demonstrates
      a fluvial connection, and therefore the absence of an intervening seaway, between
      the Panama arc and South America in middle Miocene times; the Central American
      Seaway had vanished by that time. 

PMID- 25859043
TI  - Ocean acidification and the Permo-Triassic mass extinction.
AB  - Ocean acidification triggered by Siberian Trap volcanism was a possible kill
      mechanism for the Permo-Triassic Boundary mass extinction, but direct evidence
      for an acidification event is lacking. We present a high-resolution seawater pH
      record across this interval, using boron isotope data combined with a
      quantitative modeling approach. In the latest Permian, increased ocean alkalinity
      primed the Earth system with a low level of atmospheric CO2 and a high ocean
      buffering capacity. The first phase of extinction was coincident with a slow
      injection of carbon into the atmosphere, and ocean pH remained stable. During the
      second extinction pulse, however, a rapid and large injection of carbon caused an
      abrupt acidification event that drove the preferential loss of heavily calcified
      marine biota. 

PMID- 25859044
TI  - Common variants spanning PLK4 are associated with mitotic-origin aneuploidy in
      human embryos.
AB  - Aneuploidy, the inheritance of an atypical chromosome complement, is common in
      early human development and is the primary cause of pregnancy loss. By screening
      day-3 embryos during in vitro fertilization cycles, we identified an association
      between aneuploidy of putative mitotic origin and linked genetic variants on
      chromosome 4 of maternal genomes. This associated region contains a candidate
      gene, Polo-like kinase 4 (PLK4), that plays a well-characterized role in
      centriole duplication and has the ability to alter mitotic fidelity upon minor
      dysregulation. Mothers with the high-risk genotypes contributed fewer embryos for
      testing at day 5, suggesting that their embryos are less likely to survive to
      blastocyst formation. The associated region coincides with a signature of a
      selective sweep in ancient humans, suggesting that the causal variant was either
      the target of selection or hitchhiked to substantial frequency. 

PMID- 25859045
TI  - Preventing proteostasis diseases by selective inhibition of a phosphatase
      regulatory subunit.
AB  - Protein phosphorylation regulates virtually all biological processes. Although
      protein kinases are popular drug targets, targeting protein phosphatases remains
      a challenge. Here, we describe Sephin1 (selective inhibitor of a
      holophosphatase), a small molecule that safely and selectively inhibited a
      regulatory subunit of protein phosphatase 1 in vivo. Sephin1 selectively bound
      and inhibited the stress-induced PPP1R15A, but not the related and constitutive
      PPP1R15B, to prolong the benefit of an adaptive phospho-signaling pathway,
      protecting cells from otherwise lethal protein misfolding stress. In vivo,
      Sephin1 safely prevented the motor, morphological, and molecular defects of two
      otherwise unrelated protein-misfolding diseases in mice, Charcot-Marie-Tooth 1B,
      and amyotrophic lateral sclerosis. Thus, regulatory subunits of phosphatases are
      drug targets, a property exploited here to safely prevent two protein misfolding
      diseases. 

PMID- 25859047
TI  - Love knows no boundaries.

PMID- 25859048
TI  - Erratum for the research article: "Neurotransmitter switching in the adult brain
      regulates behavior" by D. Dulcis, P. Jamshidi, S. Leutgeb, N. C. Spitzer.

PMID- 25859046
TI  - Mountain gorilla genomes reveal the impact of long-term population decline and
      inbreeding.
AB  - Mountain gorillas are an endangered great ape subspecies and a prominent focus
      for conservation, yet we know little about their genomic diversity and
      evolutionary past. We sequenced whole genomes from multiple wild individuals and
      compared the genomes of all four Gorilla subspecies. We found that the two
      eastern subspecies have experienced a prolonged population decline over the past
      100,000 years, resulting in very low genetic diversity and an increased overall
      burden of deleterious variation. A further recent decline in the mountain gorilla
      population has led to extensive inbreeding, such that individuals are typically
      homozygous at 34% of their sequence, leading to the purging of severely
      deleterious recessive mutations from the population. We discuss the causes of
      their decline and the consequences for their future survival. 

PMID- 25859049
TI  - Specificity of the anaphase-promoting complex: a single-molecule study.
AB  - Biological processes require specific enzymatic reactions, paradoxically
      involving short recognition sequences. As an example, cell-cycle timing depends
      on a sequence of ubiquitylation events mediated by the anaphase-promoting complex
      (APC) based on short redundant motifs. To understand the origin of specificity,
      we designed single-molecule fluorescence assays that capture transient
      ubiquitylation reactions. We find that the APC-mediated ubiquitylation involves a
      highly processive initial reaction on the substrate, followed by multiple
      encounters and reactions at a slower rate. The initial ubiquitylation greatly
      enhances the substrate's binding affinity in subsequent reactions, by both
      increasing the on-rate and decreasing the off-rate. We postulate that these
      cycles of positive feedback enable high specificity for substrates with short
      recognition motifs in a complex cellular environment. 

PMID- 25859051
TI  - Biochemical Evaluation of Prealbumin Levels in Patients After Peripheral Arterial
      Angiography.

PMID- 25859052
TI  - Increased Mean Platelet Volume in Familial Hypercholesterolemia.
AB  - Familial hypercholesterolemia (FH) is a genetic disorder of lipoprotein
      metabolism and increases the risk of premature cardiovascular diseases. In
      patients with FH, platelet function may be activated; however, the extent of this
      activation and its etiology are unclear. We aimed to evaluate the mean platelet
      volume (MPV), a marker of platelet activation, in patients with FH. The study
      group consisted of 164 patients with FH and 160 control patients. Controls were
      matched for age, gender, hypertension, and smoking. The MPV was significantly
      higher in patients with FH than in controls (9.2 +/- 0.4 vs 7.9 +/- 0.6 fL,
      respectively; P < .001). Platelet count was significantly lower among patients
      with FH when compared to control patients (259 +/- 51 vs 272 +/- 56 * 10(3)/L,
      respectively; P = .03). In linear regression analysis, MPV was independently
      associated only with total cholesterol (beta = .6, 95% confidence interval: 0.004
      0.008, P < .001). We have shown that MPV was increased in patients with FH and
      that it was independently associated with total cholesterol level. 

PMID- 25859050
TI  - Substrate degradation by the proteasome: a single-molecule kinetic analysis.
AB  - To address how the configuration of conjugated ubiquitins determines the
      recognition of substrates by the proteasome, we analyzed the degradation kinetics
      of substrates with chemically defined ubiquitin configurations. Contrary to the
      view that a tetraubiquitin chain is the minimal signal for efficient degradation,
      we find that distributing the ubiquitins as diubiquitin chains provides a more
      efficient signal. To understand how the proteasome actually discriminates among
      ubiquitin configurations, we developed single-molecule assays that distinguished
      intermediate steps of degradation kinetically. The level of ubiquitin on a
      substrate drives proteasome-substrate interaction, whereas the chain structure of
      ubiquitin affects translocation into the axial channel on the proteasome.
      Together these two features largely determine the susceptibility of substrates
      for proteasomal degradation. 

PMID- 25859053
TI  - A model for managing the mentally ill fixated person at major events.
AB  - OBJECTIVE: The main risk of serious harm at major public figure gatherings comes
      not from terrorists or criminal activity but from fixated persons, many of whom
      have a serious mental illness. This paper reviews a collaborative mental health
      police diversionary model for assessing and managing mentally ill individuals who
      attend major events because of their fixation on a dignitary or some
      idiosyncratic cause. METHOD: We examine the role of a multidisciplinary fixated
      threat assessment service during the pre-operational, operational and post
      operational phases of major events in Queensland in 2014, including the G20 World
      Leaders' Summit. The benefits and challenges of this unique approach are
      reviewed. RESULTS: The royal visit and G20 Finance Ministers' Meeting presented
      opportunities for the Queensland Fixated Threat Assessment Centre to develop and
      refine its approach to assessing and managing the threat posed by fixated persons
      at such events. Based on this experience, we also developed a typology to assist
      in the assessment of mentally ill people who present at public figure gatherings.
      In the week prior to the G20 Summit, six fixated people required hospitalisation
      for acute psychosis. A further 18 cases were identified during the event, one of
      whom was an involuntary patient whose leave from hospital was revoked as a
      consequence of his concerning behaviour at one of the G20 venues. There were no
      other admissions to hospital during the event, but in the remaining cases, where
      indicated, follow-up was arranged through the treating mental health service or
      general practitioner. There were no disruptive incidents involving fixated
      individuals during the G20. CONCLUSION: This novel diversionary model for
      assessing and intervening with concerning, fixated persons at major events proved
      effective in mitigating the risk posed by these individuals. It also highlighted
      the need for police, security and mental health services to consider the fixated
      in major event planning, for the safety of the event, the public and vulnerable
      mentally ill, fixated persons.

PMID- 25859054
TI  - "Everybody sounds the same": Otherwise Overlooked Ideology in Perceptual
      Dialectolgy.
AB  - When analyzing dialectology survey data, researchers usually exclude respondents
      who do not complete the survey as directed. It is argued here that such
      "unusable" responses can be considered "outlier" data and analyzed rather than be
      excluded, allowing otherwise overlooked language ideologies to emerge. Responses
      to a perceptual dialectology map survey in which 31 of the 229 respondents wrote
      comments on a map of Washington state, without drawing lines around perceived
      dialect areas as instructed, are described to illustrate this point. In the
      present data, ideologies such as the homogeneity of dialects and the importance
      of an urban/rural dichotomy surfaced. These themes are examined in terms outlined
      by Judith Irvine and Susan Gal in their discussion of how ideological processes
      are evident in language data. In addition, methodological issues regarding the
      presuppositions and orientation of respondents to the questionnaire itself are
      raised.

PMID- 25859055
TI  - Biostatistics Faculty and NIH Awards at U.S. Medical Schools.
AB  - Statistical principles and methods are critical to the success of biomedical and
      translational research. However, it is difficult to track and evaluate the
      monetary value of a biostatistician to a medical school (SoM). Limited published
      data on this topic is available, especially comparing across SoMs. Using National
      Institutes of Health (NIH) awards and American Association of Medical Colleges
      (AAMC) faculty counts data (2010-2013), together with online information on
      biostatistics faculty from 119 institutions across the country, we demonstrated
      that the number of biostatistics faculty was significantly positively associated
      with the amount of NIH awards, both as a school total and on a per faculty basis,
      across various sizes of U.S. SoMs. Biostatisticians, as a profession, need to be
      proactive in communicating and advocating the value of their work and their
      unique contribution to the long-term success of a biomedical research enterprise.

PMID- 25859056
TI  - A stochastic agent-based model of pathogen propagation in dynamic multi
      relational social networks.
AB  - We describe a general framework for modeling and stochastic simulation of
      epidemics in realistic dynamic social networks, which incorporates heterogeneity
      in the types of individuals, types of interconnecting risk-bearing relationships,
      and types of pathogens transmitted across them. Dynamism is supported through
      arrival and departure processes, continuous restructuring of risk relationships,
      and changes to pathogen infectiousness, as mandated by natural history; dynamism
      is regulated through constraints on the local agency of individual nodes and
      their risk behaviors, while simulation trajectories are validated using system
      wide metrics. To illustrate its utility, we present a case study that applies the
      proposed framework towards a simulation of HIV in artificial networks of
      intravenous drug users (IDUs) modeled using data collected in the Social Factors
      for HIV Risk survey.

PMID- 25859057
TI  - Microbial community composition shapes enzyme patterns in topsoil and subsoil
      horizons along a latitudinal transect in Western Siberia.
AB  - Soil horizons below 30 cm depth contain about 60% of the organic carbon stored in
      soils. Although insight into the physical and chemical stabilization of soil
      organic matter (SOM) and into microbial community composition in these horizons
      is being gained, information on microbial functions of subsoil microbial
      communities and on associated microbially-mediated processes remains sparse. To
      identify possible controls on enzyme patterns, we correlated enzyme patterns with
      biotic and abiotic soil parameters, as well as with microbial community
      composition, estimated using phospholipid fatty acid profiles. Enzyme patterns
      (i.e. distance-matrixes calculated from these enzyme activities) were calculated
      from the activities of six extracellular enzymes (cellobiohydrolase, leucine
      amino-peptidase, N-acetylglucosaminidase, chitotriosidase, phosphatase and
      phenoloxidase), which had been measured in soil samples from organic topsoil
      horizons, mineral topsoil horizons, and mineral subsoil horizons from seven
      ecosystems along a 1500 km latitudinal transect in Western Siberia. We found that
      hydrolytic enzyme activities decreased rapidly with depth, whereas oxidative
      enzyme activities in mineral horizons were as high as, or higher than in organic
      topsoil horizons. Enzyme patterns varied more strongly between ecosystems in
      mineral subsoil horizons than in organic topsoils. The enzyme patterns in topsoil
      horizons were correlated with SOM content (i.e., C and N content) and microbial
      community composition. In contrast, the enzyme patterns in mineral subsoil
      horizons were related to water content, soil pH and microbial community
      composition. The lack of correlation between enzyme patterns and SOM quantity in
      the mineral subsoils suggests that SOM chemistry, spatial separation or physical
      stabilization of SOM rather than SOM content might determine substrate
      availability for enzymatic breakdown. The correlation of microbial community
      composition and enzyme patterns in all horizons, suggests that microbial
      community composition shapes enzyme patterns and might act as a modifier for the
      usual dependency of decomposition rates on SOM content or C/N ratios.

PMID- 25859058
TI  - Increased decomposer diversity accelerates and potentially stabilises litter
      decomposition.
AB  - Little is known about the effect of decomposer diversity on litter decomposition
      in alpine areas. Especially under the premise that alpine ecosystems are very
      sensitive to global change and are currently undergoing extensive land-use
      changes, a better understanding is needed to predict how environmental change
      will affect litter decomposition. A mesocosm experiment was conducted to compare
      the effects of the most common and functionally diverse invertebrates
      (earthworms, millipedes and sciarid larvae) found in alpine soils on
      decomposition rates and to assess how decomposer diversity affects litter
      decomposition. Experimental and estimated (i.e. projected to field decomposer
      biomass) litter mass loss was 13-33% higher in the three-species treatment.
      Notably, the variability in decomposition was greatly reduced when decomposer
      diversity was high, indicating a portfolio effect. Our results suggest that
      invertebrate decomposer diversity is essential for sustaining litter
      decomposition in alpine areas and for the stability of this service.

PMID- 25859059
TI  - Localization of hsp27 in the rat submandibular gland following the application of
      various surgical treatments.
AB  - Salivary glands repair and regenerate following various types of injuries and
      surgical procedures. However, the tissue responses induced in the contralateral
      glands have yet to be elucidated in detail. Hsp27, a member of the heat-shock
      protein (Hsp) family, is strongly expressed in physiological environments,
      particularly during development. Hsp27 was previously shown to play a role in the
      regulation of acinar cell proliferation and differentiation in the rat
      submandibular gland. The present study performed the following surgical
      treatments on the right submandibular glands of adult rats: 1) duct ligation
      followed by unligation after one week; 2) partial sialoadenectomy; and 3) total
      sialoadenectomy. Immunohistochemistry for Hsp27 and Ki67 was performed in the
      experimental and normal contralateral glands, and localization was histologically
      and morphometrically analyzed. The results obtained revealed the localization of
      Hsp27 to the intercalated duct in the submandibular glands of non-treated rats.
      The expression of Hsp27 was strongly induced in both the uninjured contralateral
      control glands as well as treated glands of experimental rats regardless of the
      surgical procedure performed. The number of Hsp27-immunopositive cells increased
      rapidly following surgery, and subsequently returned to the same level as that in
      non-treated rats after 4 weeks. However, no marked changes were observed in the
      number of Ki67-immunopositive proliferating cells. Therefore, the change in the
      number of Hsp27-immunopositive cells may have contributed to compensatory
      hypertrophy. The results of the present study indicate that the expression of
      Hsp27 in the intercalated duct in the submandibular gland may play a role in the
      differentiation of acinar cells. 

PMID- 25859060
TI  - A Decrease in Glomerular Endothelial Cells and Endothelial-mesenchymal Transition
      during Glomerulosclerosis in the Tensin2-deficient Mice (ICGN strain).
AB  - The ICR-derived glomerulonephritis (ICGN) mouse is a unique model of nephrotic
      syndrome, and albuminuria becomes evident in a neonatal stage, due to a genetic
      mutation of tensin2. We previously provided evidence that an apparent decrease in
      nephrin, caused by tensin2-deficiencient states, leads to podocytopathy,
      albuminuria and eventually, chronic renal failure. In general, glomerular
      endothelial cells (ECs) function as a barrier through tight attachment of
      glomerular basement membrane to podocytes, while decreased ECs can worsen renal
      failure. Nevertheless, it is still unknown whether glomerular ECs are altered
      under the tensin-2-deficient states during the manifestation of chronic renal
      failure. Herein, we examined the changes of glomerular ECs, with focus on the
      expression of PECAM-1 and VE-cadherin (EC-specific markers), or of alpha-SMA
      (myofibroblast marker) in this mouse model by histological methods. Compared with
      the non-nephrotic (+/nep) mice, the nephrotic (nep/nep) mice exhibited the
      reduced expression of PECAM-1, or of VE-cadherin, in glomerular area. Notably,
      some glomerular ECs showed the positive stainings for both PECAM-1 and alpha-SMA,
      suggesting endothelial-to-mesenchymal transition (EndoMT) during progression of
      glomerular sclerosis. This is the first report showing that a decrease in
      glomerular ECs, at least in part, via EndoMT is involved in tensin2-deficient
      pathological conditions. 

PMID- 25859061
TI  - Immuno- and Enzyme-histochemistry of HRP for Demonstration of Blood Vessel
      Permeability in Mouse Thymic Tissues by "In Vivo Cryotechnique".
AB  - It is difficult to understand the in vivo permeability of thymic blood vessels,
      but "in vivo cryotechnique" (IVCT) is useful to capture dynamic blood flow
      conditions. We injected various concentrations of horseradish peroxidase (HRP)
      with or without quantum dots into anesthetized mice via left ventricles to
      examine architectures of thymic blood vessels and their permeability at different
      time intervals. At 30 sec after HRP (100 mg/ml) injection, enzyme reaction
      products were weakly detected in interstitium around some thick blood vessels of
      corticomedullary boundary areas, but within capillaries of cortical areas. At 1
      and 3 min, they were more widely detected in interstitium around all thick blood
      vessels of the boundary areas. At 10 min, they were diffusely detected throughout
      interstitium of cortical areas, and more densely seen in medullary areas. At 15
      min, however, they were uniformly detected throughout interstitium outside blood
      vessels. At 30 min, phagocytosis of HRP by macrophages was scattered throughout
      the interstitium, which was accompanied by decrease of HRP reaction intensity in
      interstitial matrices. Thus, time-dependent HRP distributions in living mice
      indicate that molecular permeability and diffusion depend on different areas of
      thymic tissues, resulting from topographic variations of local interstitial flow
      starting from corticomedullary areas. 

PMID- 25859062
TI  - Heterogeneous Immunoreactivity of Emerin, a Nuclear Envelope LEM-domain Protein,
      in Normal Thyroid Follicles.
AB  - Emerin is a LEM domain-containing integral membrane protein of the vertebrate
      nuclear envelope. Recently it has been reported that emerin regulates tissue
      specific gene/protein expression. We studied the relationship between emerin
      expression and follicle function in normal and hyperplastic human thyroid tissues
      using immunohistochemistry and statistical methods. Emerin immunoreactivity was
      heterogeneous among follicular cells and follicles in normal thyroid tissue. It
      tended to be strong in the nuclei of tall follicular cells of small follicles and
      weak or negative in the nuclei of flat follicular cells of large follicles.
      Follicles with strong expression of emerin were also strongly positive for
      thyroglobulin (Tg) and thyroxine (T4) in follicular cells and colloid substance,
      suggesting active functioning follicles. In contrast, large follicles with weak
      expression of emerin were also weak or negative for Tg and T4. Emerin
      immunoreactivity was strong in almost all nuclei of hyperplastic follicular cells
      in Graves' disease tissues. These findings suggest that emerin expression may be
      related with follicular function and may contribute to the understanding of
      hormonogenesis in normal thyroid follicles. 

PMID- 25859063
TI  - High Expression of SQSTM1/p62 Protein Is Associated with Poor Prognosis in
      Epithelial Ovarian Cancer.
AB  - High expression of SQSTM1/p62 (p62) protein, which functions as a hub for various
      cellular signaling pathways, has been detected in several human cancers. However,
      the clinicopathological impact of high p62 expression is largely unknown in
      epithelial ovarian cancer (EOC). Here, the expression level of p62 in primary
      EOCs (n=266) was assessed by immunohistochemistry, and its clinical significance
      was analyzed. Univariate and multivariate analyses were used to determine the
      impact of p62 expression on overall survival. p62 was expressed in the cytoplasm
      (Cyto) and/or nucleus (Nuc) in primary EOCs, and an expression subtype
      (Cyto(High)/Nuc(Low)), showing high expression in the cytoplasm but low
      expression in the nucleus, was significantly correlated with serous carcinoma
      (P<0.001), advanced stage (P=0.005), presence of residual tumor (P<0.001), and
      low overall survival rate (P=0.013). Furthermore, in serous carcinomas (n=107),
      the p62 Cyto(High)/Nuc(Low) subtype was significantly correlated with low overall
      survival rate (P=0.019) as an independent factor (P=0.044). Thus, our findings
      suggest that high expression of cytoplasmic p62 may be a novel prognostic
      biomarker in EOC, particularly in serous carcinoma. 

PMID- 25859064
TI  - Expression of Nephrin Homologue in the Freshwater Planarian, Dugesia japonica.
AB  - Excretory organs contain epithelial cells that form a filtration membrane
      specialized for ultrafiltration to produce primary urine. In vertebrates, the
      filtration membrane is made up of slit diaphragm (SD) formed by glomerular
      podocytes. Basal metazoans such as flatworms are also known have filtration
      epithelial cells, called flame cells, which exhibit SD-like structures. The
      molecular components of podocyte SD have been studied in detail, while those of
      the SD-like structures in basal metazoans including flatworms remain to be
      clarified. To determine whether the SD-like structures in flatworms have
      molecular components common to the SD in vertebrate podocytes, we examined the
      expression of gene homologue for mammalian nephrin, which encodes an essential
      transmembrane protein that participates in the formation of the SD, in a species
      of flatworms, planarian (Dugesia japonica). Flame cells were distributed
      throughout the entire body of the planarian, but the nephrin-expressing cells
      identified by in situ hybridization were mainly detected at body periphery
      excluding head region. The distribution pattern of nephrin-expressing cells was
      similar to that of proliferating cell nuclear antigen-expressing neoblasts, which
      are pluripotent stem cells characteristic to planarians. These findings indicated
      that the SD-like structures can be formed without the Nephrin protein in
      planarian flame cells. 

PMID- 25859065
TI  - Accumulation of Platinum Nanoparticles by Sinapis alba and Lepidium sativum
      Plants.
AB  - Nanoparticles (NPs) are commonly used, and concerns about their possible adverse
      effects are being voiced as well. However, little is known about the fates of NPs
      released to the environment. The aim of the study was to (i) evaluate the ability
      of Sinapis alba and Lepidium sativum plants to take up platinum nanoparticles (Pt
      NPs) and translocate them to aboveground organs, (ii) compare the accumulation
      efficiency of different forms of platinum and (iii) identify the forms in which
      platinum is stored in plant tissues. Plants were cultivated on medium
      supplemented with different concentrations of Pt-NPs and [Pt(NH3)4](NO3)2.
      Platinum content in plants was determined using inductively coupled plasma mass
      spectrometry. For the identification of the presence of Pt-NPs in plant tissues,
      gamma spectrometry following iron irradiation was applied. It was found that L.
      sativum and S. alba are tolerant to applied concentrations of Pt-NPs and have an
      ability to take up platinum from the medium and translocate it to aboveground
      organs. The highest concentration of platinum was observed in plant roots
      (reaching 8.7 g kg-1 for S. alba). We tentatively conclude that platinum is
      accumulated as nanoparticles. The obtained results suggest future application of
      plants for phytoremediation and recovery of noble metal nanoparticles.

PMID- 25859066
TI  - "Deficits Don't Matter": Abundance, Indebtedness and American Culture.
AB  - If deficits, nor defaults, don't really matter anymore, what sign of our times is
      it? What has changed from the days that Franklin Delano Roosevelt risked the
      fragile economic recovery from the great depression by returning, in 1937, to the
      standard of his economic orthodoxy, a belief in fiscal rectitude and anaversion
      to debts and deficits? If that was a sign of a certain American character, what
      has happened to it? A massive shift in public culture must have occurred,
      affecting people's views on public probity and political rectitude. The following
      is an attempt to trace some of the main shifts on the way to our present
      quandary.

PMID- 25859067
TI  - Links between Adolescents' Closeness to Adoptive Parents and Attachment Style in
      Young Adulthood.
AB  - This study examined whether adolescents' closeness to adoptive parents (APs)
      predicted attachment styles in close relationships outside their family during
      young adulthood. In a longitudinal study of domestic infant adoptions, closeness
      to adoptive mother and adoptive father was assessed in 156 adolescents (M = 15.7
      years). Approximately nine years later (M = 25.0 years), closeness to parents was
      assessed again as well as attachment style in their close relationships.
      Multilevel modeling was used to predict attachment style in young adulthood from
      the average and discrepancy of closeness to adolescents' adoptive mothers and
      fathers and the change over time in closeness to APs. Less avoidant attachment
      style was predicted by stronger closeness to both APs during adolescence.
      Increased closeness to APs over time was related to less anxiety in close
      relationships. Higher closeness over time to either AP was related to less
      avoidance and anxiety in close relationships.

PMID- 25859068
TI  - Orientation of PVDF alpha and gamma crystals in nanolayered films.
AB  - Wide-angle X-ray scattering in conjunction with pole figure technique was used to
      study the texture of poly(vinylidene fluoride) (PVDF) alpha and gamma phase
      crystals in nanolayered polysulfone/poly(vinylidene fluoride) films (PSF/PVDF)
      produced by layer-multiplying coextrusion. In all as-extruded PSF/PVDF films, the
      PVDF nanolayers crystallized into the alpha phase crystals. A large fraction of
      those crystals was oriented with macromolecular chains perpendicular to the
      PSF/PVDF interface as evidenced from the (021) pole figures. Further refinement
      of the texture occurs during isothermal recrystallization at 170  degrees C in
      conjunction with transformation of alpha to gamma crystals. The gamma crystals
      orientation was probed with the (004) pole figures showing the c-axis of PVDF
      gamma crystals perpendicular to the PSF/PVDF interface. The thinner the PVDF
      layers the stronger the orientation of gamma crystals. It was proven that the X
      ray reflections from the (021) planes of alpha crystals and from the (004) planes
      of gamma crystals are not overlapped with other reflections and can be
      effectively used for the texture determination of PVDF nanolayers in multilayered
      PSF/PVDF films.

PMID- 25859069
TI  - First Order Dominance Analysis: Child Wellbeing in the Democratic Republic of
      Congo.
AB  - This paper performs a multidimensional first order dominance analysis of child
      wellbeing in the Democratic Republic of Congo (DRC). This methodology allows the
      ordinal ranking of the 11 provinces of the DRC in terms of their wellbeing based
      upon the probability of their domination. This empirical application obviates the
      need to adopt a weighting scheme for the deprivation indicators or to rely on the
      signs of other cross-derivatives for comparison. We execute a bootstrap linear
      programming algorithm on seven deprivation indicators for three age groups of
      children derived from the DRC 2007 Standard Demographic and Health Survey. The
      results reveal widespread disparities in child wellbeing in the DRC.

PMID- 25859070
TI  - Writing and publishing a scientific paper: Facts, Myths and Realities.

PMID- 25859071
TI  - Antimicrobial use and antimicrobial resistance in nosocomial pathogens at a
      tertiary care hospital in Pune.
AB  - BACKGROUND: Resistance to antimicrobial agents is emerging in wide variety of
      nosocomial and community acquired pathogens. Widespread and often inappropriate
      use of broad spectrum antimicrobial agents is recognized as a significant
      contributing factor to the development and spread of bacterial resistance. This
      study was conducted to gain insight into the prevalent antimicrobial prescribing
      practices, and antimicrobial resistance pattern in nosocomial pathogens at a
      tertiary care hospital in Pune, India. METHODS: Series of one day cross sectional
      point prevalence surveys were carried out on four days between March and August
      2014. All eligible in patients were included in the study. A structured data
      entry form was used to collect the data for each patient. Relevant samples were
      collected for microbiological examination from all the clinically identified
      hospital acquired infection cases. RESULTS: 41.73% of the eligible patients (95%
      CI: 39.52-43.97) had been prescribed at least one antimicrobial during their stay
      in the hospital. Beta-lactams (38%) were the most prescribed antimicrobials,
      followed by Protein synthesis inhibitors (24%). Majority of the organisms
      isolated from Hospital acquired infection (HAI cases) were found to be resistant
      to the commonly used antimicrobials viz: Cefotaxime, Ceftriaxone, Amikacin,
      Gentamicin and Monobactams. CONCLUSION: There is need to have regular
      antimicrobial susceptibility surveillance and dissemination of this information
      to the clinicians. In addition, emphasis on the rational use of antimicrobials,
      antimicrobial rotation and strict adherence to the standard treatment guidelines
      is very essential.

PMID- 25859072
TI  - Transvaginal sonography versus hysteroscopy in evaluation of abnormal uterine
      bleeding.
AB  - BACKGROUND: Abnormal uterine bleeding (AUB) accounts for 33% of female patients
      referred to gynaecologists. Common causes of AUB include endometrial polyps,
      endometrial hyperplasia, submucous fibroids and anovulation. Accurate diagnosis
      of the cause of AUB can reduce the frequency of hysterectomy. This study was
      aimed at assessing the usefulness of TVS in comparison with hysteroscopy in AUB
      evaluation. METHODS: 100 female patients with AUB were enrolled in the study.
      Each patient was subjected to TVS where uterine cavity was studied in detail and
      hysteroscopy under anaesthesia using saline as distension medium. Sensitivity,
      specificity and predictive value of TVS as compared to hysteroscopy were
      calculated. Subgroup analysis within each group was also performed. RESULTS:
      Menorrhagia was the commonest presenting symptom in the study population (n = 58)
      followed by metrorrhagia, menometrorrhagia and continuous bleeding >21 days. 74
      female patients had normal size uterus. In 57 patients, the uterine cavity was
      normal on TVS. Thickened endometrium, endometrial polyp and submucous fibroids
      were seen in 19, 16 and 6 patients respectively. Hysteroscopy showed normal
      cavity in 59 female patients and polypoidal endometrium, polyps or submucous
      fibroids in 41. TVS was found to have high sensitivity and specificity (95.23 and
      94.82 respectively) and high positive and negative predictive value. Strength of
      agreement between TVS and hysteroscopy was high (kappa value 0.898). CONCLUSION:
      TVS is recommended as first line investigation in AUB. If TVS shows normal
      cavity, further evaluation can be omitted and patient started directly on medical
      treatment for her symptoms.

PMID- 25859073
TI  - Major laparoscopic surgery under regional anesthesia: A prospective feasibility
      study.
AB  - BACKGROUND: Laparoscopic surgeries have attained the status of a gold standard
      for most of the abdominal pathology; we therefore performed this study to assess
      feasibility and safety of major laparoscopic surgeries like laparoscopic
      cholecystectomy (LC) and laparoscopic assisted vaginal hysterectomy (LAVH)/total
      laparoscopic hysterectomy (TLH) under regional anesthesia that is combined spinal
      epidural anesthesia (CSE) with normal pressure pneumoperitoneum using intrathecal
      fentanyl with bupivacain. METHODS: In a zonal government hospital, 50 patients
      were selected prospectively for LC and LAVH/TLH, under normal pressure (12 mmHg)
      pneumoperitoneum and under CSE over a span of fifteen months. Injection
      bupivacaine (0.5%) and 20 MUg of fentanyl were used for spinal anesthesia. Plain
      bupivacaine (0.5%) was used for epidural anesthesia. RESULTS: We successfully
      performed the operations in 48 patients without major complications. CSE was
      converted to general anesthesia in two patients due to distressing shoulder tip
      pain. Age varied between 25 and 70 years. Duration of operation time (skin to
      skin) was between 50 and 170 min. Five patients had urinary retention and one
      developed localized pruritis. There was no incidence of respiratory depression,
      aspiration or headache. CONCLUSION: Laparoscopic surgeries with normal pressure
      CO2 pneumoperitoneum are feasible and safe under CSE. Incidence of postoperative
      shoulder pain was minimal due to use of intrathecal fentanyl and complications
      were less and easily manageable.

PMID- 25859074
TI  - The ABC of diabetes. How many patients are able to achieve the goal laid down by
      American Diabetes Association?
AB  - BACKGROUND: To study the number of patients with Type 2 Diabetes Mellitus who
      achieve the glycemic, blood pressure and LDL-Cholesterol targets as per American
      Diabetes Association, Standard of Care for Management of Diabetes. METHODS:
      Hundred patients of Type 2 Diabetes mellitus were recruited from December 2008 to
      January 2009 from an Endocrinology OPD of tertiary care hospital and followed up
      for six months. Glycosylated hemoglobin (HbA1c), blood pressure (BP) and LDL
      Cholesterol (LDL) were estimated at baseline and prevalence of those at target
      (HbA1c <7%, BP < 130/80 mm Hg, LDL < 100 mg/dl) was documented and repeated at
      three and six months to monitor improvement in the number of patients at target
      and trend in improvement of individual parameters. RESULTS: The percentage of
      patients at target at baseline and six months for HbA1c was (45% vs. 55% p =
      0.101), BP < 130/80 mm Hg (27% vs. 25%) and LDL <100 mg/dl (37% vs. 40% p =
      0.386). All three parameters were at target in one patient and three patients at
      six months period. Mean values at baseline and six months of HbA1c 7.46% (95% CI
      7.17-7.75) vs 7.21% (95% CI 6.9-7.52), Systolic BP 138 mm Hg (95% CI 135-141),
      Diastolic BP 86 mm Hg (95% CI 84-86) and LDL 114 mg/dl (95%CI 107-121) vs. 110
      mg/dl (95%CI 105-116) did not show significant improvement (p for trend).
      CONCLUSION: Standards of care for HbA1c, blood pressure and LDL remains to be
      achieved in majority of the diabetic patients.

PMID- 25859075
TI  - Seroprevalence of TORCH infections in antenatal and HIV positive patient
      populations.
AB  - BACKGROUND: The TORCH (Toxoplasma gondii, Rubella, Cytomegalovirus (CMV) and the
      Herpes Simplex Virus) cause range of diseases in pregnant women and HIV patients
      and lead to adverse fetal outcomes when not treated on time, in HIV positive can
      cause life threating infections. There is inadequate data available of these
      infections in India. METHODS: A retrospective study was undertaken to determine
      the seroprevalence of the TORCH infections in antenatal and HIV/AIDS patients at
      a tertiary care centre. The laboratory data pertaining to the period Jan 2012-May
      2014 was analyzed. The study population involved 162 antenatal cases and 729
      HIV/AIDS patients under review at an ART centre. Laboratory testing was done for
      the presence of IgM and IgG antibodies against the TORCH infections by ELISA
      method. RESULTS: Among the antenatal cases, 30 (18.52%) samples were found to be
      seropositive for Toxoplasma IgM, CMV IgM antibodies were found in 47 (29.01%)
      samples, HSV IgM antibodies were found in 12 (7.40%) samples, Rubella IgM
      antibodies were found in 13 (8.02%) samples, indicating recent infection. Among
      the HIV/AIDS cases, indicative of recent or current infection, 160 (21.94%)
      samples were positive for Toxoplasma IgM, CMV IgM was found in 99 (13.58%), HSV
      IgM antibodies were found in 98 (13.44%) and Rubella IgM in 47 (6.44%).
      CONCLUSIONS: The study showed a high seroprevalence of the infections caused by
      the TORCH complex amongst pregnant women and HIV/AIDS patients despite improved
      hygiene conditions and health awareness. Maximum seroprevalence for CMV was
      observed followed by Rubella and HSV infection.

PMID- 25859076
TI  - Emergence of multidrug resistant enterococci at a tertiary care centre.
AB  - BACKGROUND: Enterococci have assumed great clinical importance because of their
      increasing resistance to various antimicrobial agents. Thus, knowledge about the
      antibiogram of these multidrug resistant isolates is of utmost importance in
      formulating an effective antibiotic policy to treat these infections and reducing
      the morbidity and mortality. Aim of this study was to assess the antimicrobial
      resistance pattern of enterococci and determine the prevalence of multidrug
      resistance among them. METHODS: This cross sectional study was carried out from
      August 2011 to February 2014, in which 200 non-repetitive clinical isolates of
      enterococci were included. Antimicrobial susceptibility testing was done by disc
      diffusion method. Minimum inhibitory concentration (MIC) of gentamicin,
      streptomycin, vancomycin, teicoplanin and linezolid was determined by E-test
      method. RESULTS: The prevalence of multidrug resistance among enterococcal
      isolates was found to be 63%. Varying levels of resistance was seen to various
      antibiotics. Most of the isolates were resistant to penicillin (95%), ampicillin
      (95%) and cotrimoxazole (90%). High level aminoglycoside resistance (HLAR) and
      glycopeptide resistance was seen in 39% and 14% isolates respectively. Only 4
      isolates (2%) were found to be resistant to linezolid. CONCLUSION: The prevalence
      of multidrug resistance among enterococci was found to be 63%, the resistance
      being more common in Enterococcus faecium as compared to Enterococcus faecalis.
      The study highlights the emergence and increased prevalence of multidrug
      resistant enterococci which pose a serious therapeutic challenge.

PMID- 25859077
TI  - Comparative analysis of changes in MR imaging of pre and post intrauterine
      progesterone implants in adenomyosis cases.
AB  - BACKGROUND: Magnetic Resonance Imaging (MRI) plays an important role in the
      evaluation and management of adenomyosis. In this study, we first diagnosed the
      adenomyosis on MRI and then we analyzed the MRI changes in the uterus in pre and
      post intrauterine progesterone implants cases. METHOD: All the patients with
      clinical diagnosis of menorrhagia or dysmenorrhea were screened by
      Ultrasonography (USG) of the pelvis. Patients with heterogeneous echo texture of
      the uterus were then evaluated by the MRI of the pelvis. All patients with MRI
      findings suggestive of adenomyosis formed the study group. RESULT: On MRI study
      60 patients were diagnosed as adenomyosis, 68.33% had diffuse adenomyosis and
      31.66% had focal adenomyosis. 83% of diagnosed adenomyosis cases had high
      intensity signal foci which were seen in 75% cases of diffuse adenomyosis and
      100% cases of focal adenomyosis. 50 diagnosed adenomyosis cases were then
      reviewed after 03 months, 06 months and 12 months to see for any change in the
      MRI findings in the post intrauterine implant cases. On follow up MRI after post
      progesterone intrauterine implant, 50% of the cases showed reduction in the high
      intensity signals, 10% of the cases showed mild reduction in the junctional zone
      thickness with no significant change in the uterine size. CONCLUSIONS: It is
      inferred that MR imaging is not only helpful in diagnosing but also helpful in
      monitoring the effects of hormonal therapy in adenomyosis.

PMID- 25859078
TI  - A study of assessment of patient safety climate in tertiary care hospitals.
AB  - BACKGROUND: Medical errors are being detected with increasing frequency in
      healthcare environment, in many cases leading to patient harm. Measurement and
      improvement of patient safety climate has been identified as a strategic effort
      towards addressing this vital issue. METHOD: Safety Attitude Questionnaire (SAQ),
      validated by previous research was administered to 300 respondents in three
      tertiary care hospitals of India, the respondents representing various categories
      of healthcare workers and variations in safety scale score was analyzed by
      various statistical tools. RESULTS: No variation was observed in the Patient
      Safety Index score among the study hospitals. However, significant variations
      were observed among different categories of healthcare workers across dimensions
      of Teamwork, Perception of Management and Stress Recognition. Multiple Regression
      models identified Teamwork and Perception of Management to have significant
      correlation with Patient Safety Index Score. CONCLUSION: Patient Safety Climate
      can be effectively assessed and such assessment utilized for focused improvement
      efforts towards safety in healthcare organizations.

PMID- 25859079
TI  - Real time ultrasound-guided percutaneous tracheostomy: Is it a better option than
      bronchoscopic guided percutaneous tracheostomy?
AB  - BACKGROUND: The purpose of this study was to evaluate the efficacy of ultrasound
      guided percutaneous tracheostomy (USPCT) and bronchoscopic guided percutaneous
      tracheostomy (BPCT) and the incidence of complications in critically ill, obese
      patients. METHODS: Seventy four consecutive patients were included in a
      prospective study and randomly divided into USPCT and BPCT. Incidence of
      complications, ease and efficacy were compared in obese USPCT (n = 38)and BPCT (n
      = 36). Results are expressed as the median (25th-75th percentile) or number
      (percentage). RESULTS: The median times for tracheostomy were 12 min (9-14) in
      USPCT patients and 18 min (12-21.5) in BPCT (p = 0.05). The overall complication
      rate was higher in BPCT than USPCT patient group (75% vs. 321%, p < 0.05). Most
      complications were minor (hypotension, desaturation, tracheal cuff puncture and
      minor bleeding) and of higher number in the BPCT. Ultrasound-guided PCT was
      possible in all enrolled patients and there were no surgical conversions or
      deaths. CONCLUSIONS: This study demonstrated that real US-guided PCT is a
      favourable alternative to BPCT with a low complication rate and ease, thus
      proving more efficacious. A US examination provides information on cervical
      anatomy, vasculature etc. and hence modifies and guides choice of the PCT
      puncture site.

PMID- 25859080
TI  - Clinical evaluation of immediate loading of titanium orthodontic implants.
AB  - BACKGROUND: Skeletal anchorage using dental implants, miniplates, miniscrews and
      microscrews provides an absolute anchorage for tooth movement. Miniscrew and
      microscrew implants have many benefits such as ease of placement and removal and
      immediate orthodontic force application. METHODS: Fifteen subjects in the
      permanent dentition with an overjet >=6 mm received treatment with the 0.018-inch
      pre-adjusted edgewise appliance system (Roth prescription) and extraction of all
      first premolars. Titanium orthodontic implants were placed in both the upper
      quadrants and were immediately loaded with elastic chain from the implant head to
      the sectional arch wire. RESULT: The overall success rate of immediate loaded
      titanium orthodontic micro implants (OMI) in the present study was 83.33%, with a
      mean chairside time of 15.33 min of placing two implants in each patient. Peri
      implant inflammation was the only complication observed. Most failures were in
      the initial part of the study. There was no significant difference in the success
      rate of implants based on sex, side of placement (right or left) and type of
      malocclusion. CONCLUSION: The OMIs used in the present study proved to be
      effective and well tolerated in producing immediate orthodontic anchorage for the
      retraction.

PMID- 25859081
TI  - HPV vaccine: Current status and future directions.
AB  - HPV Vaccine was introduced to prevent cervical cancer known to be caused by
      infection with one or more of the high risk subtypes of the Human papilloma virus
      (HPV). Since introduction, trials have proven its efficacy in preventing Cervical
      intraepithelial neoplasia (CIN) beyond doubt and its effectiveness in preventing
      cervical cancer though presumptive is reasonably certain as per mathematical
      modelling. It also prevents other HPV related anogenital and oropharyngeal
      malignancies in both sexes. HPV vaccines have courted many controversies related
      to its efficacy, safety, ideal age of vaccination, use in HPV infected
      individuals and use in males. The currently available vaccines are based on L1
      Viral like particles (VLP) and hence highly species specific, thermolabile,
      costly and are purely prophylactic. The quest for a cheaper, thermostable and
      broad spectrum vaccine has led to many newer prophylactic vaccines. Therapeutic
      vaccines were born out of the inescapable necessity considering high HPV related
      morbidity projected in the non HPV naive population. Therapeutic vaccines would
      immediately reduce this burden and also help in the management of HPV related
      cancers alone or as part of combination strategies. Ongoing research is aimed at
      a total control over HPV related malignancies in the near future. 

PMID- 25859082
TI  - Antimicrobial resistance: A public health challenge.
AB  - Antimicrobial resistance has become a global concern. Though an evolutionary
      phenomenon, it is promulgated by faulty human behaviours. It is a growing concern
      ever since first reported in 1940s. Today, a plethora of newer generation
      antimicrobials have become ineffective against previously susceptible organisms.
      This is a huge challenge for health care managers all across the globe,
      compounded by the "discovery void" in the field of development of new
      antibiotics. If proper steps are not taken presently, the lurking fear of
      reaching a therapeutic dead end will become a reality. This paper aims at
      describing the pandemic of AMR from a public health perspective and suggesting
      strategies to deal with it in an effective and collaborative manner. 

PMID- 25859083
TI  - Detection of human papillomavirus in women attending Pap cervical screening camp
      at a peripheral hospital of North-Eastern India.
AB  - Human papillomavirus (HPV) associated cervical cancer is the leading cause of
      deaths in India. However, cytological/HPV screening may result in early detection
      of cervical cancer, resulting in early treatment and reduced mortality. Although
      reports related to general population is available, data on HPV prevalence among
      women attending AFMS health care facilities is scarce. Cervical samples were
      collected for cytological staining by Pap test and molecular detection by PCR,
      genotyping by HPV specific primers and sequencing. Apart from finding of atypical
      cells of undetermined significance (ASCUS) in one subject, no evidence of
      malignancy was observed. A high prevalence of HPV was found in this study group,
      which was intermediate between previous reports from general population and
      cervical cancer patients. All the subjects had infection of high risk HPV type16.
      HPV prevalence was found similar between different age groups. Although, none of
      the study subjects had malignant changes, but due to high prevalence of high risk
      HPV infection and other associated risk factors, these subjects might be at an
      elevated risk of developing cervical cancer. Regular follow-up of these patients
      who were detected HPV positive are required to screen for cervical malignancy. 

PMID- 25859084
TI  - Anaesthetic management of an esophageal stent perforation of the left main
      bronchus.

PMID- 25859085
TI  - A case of bilateral developmental cataract with non-syndromic cyanotic congenital
      heart disease.

PMID- 25859086
TI  - Spontaneous perforation of pyometra: A rare cause of diffuse peritonitis.

PMID- 25859087
TI  - Interstitial implantation in a setting of recurrent ectopic pregnancy: A rare
      combination.

PMID- 25859088
TI  - Histiocytosis.

PMID- 25859089
TI  - Unique complication during central venous catheterisation: "Needle dislodgement".

PMID- 25859090
TI  - Letter to editor.

PMID- 25859091
TI  - Reply.

PMID- 25859092
TI  - Reply.

PMID- 25859093
TI  - Technology acquisition in radiodiagnosis: Pros and cons.

PMID- 25859094
TI  - Reply.

PMID- 25859095
TI  - Letter to the editor.

PMID- 25859096
TI  - Tax authorities' interaction with taxpayers: A conception of compliance in social
      dilemmas by power and trust.
AB  - Tax compliance represents a social dilemma in which the short-term self-interest
      to minimize tax payments is at odds with the collective long-term interest to
      provide sufficient tax funds for public goods. According to the Slippery Slope
      Framework, the social dilemma can be solved and tax compliance can be guaranteed
      by power of tax authorities and trust in tax authorities. The framework, however,
      remains silent on the dynamics between power and trust. The aim of the present
      theoretical paper is to conceptualize the dynamics between power and trust by
      differentiating coercive and legitimate power and reason-based and implicit
      trust. Insights into this dynamic are derived from an integration of a wide range
      of literature such as on organizational behavior and social influence.
      Conclusions on the effect of the dynamics between power and trust on the
      interaction climate between authorities and individuals and subsequent individual
      motivation of cooperation in social dilemmas such as tax contributions are drawn.
      Practically, the assumptions on the dynamics can be utilized by authorities to
      increase cooperation and to change the interaction climate from an antagonistic
      climate to a service and confidence climate.

PMID- 25859097
TI  - Emotion Knowledge, Loneliness, Negative Social Experiences, and Internalizing
      Symptoms Among Low-Income Preschoolers.
AB  - Children with poor emotion knowledge (EK) skills are at risk for externalizing
      problems; less is known about early internalizing behavior. We examined multiple
      facets of EK and social-emotional experiences relevant for internalizing
      difficulties, including loneliness, victimization, and peer rejection, in Head
      Start preschoolers (N = 134; M = 60 months). Results based on multiple informants
      suggest that facets of EK are differentially related to negative social-emotional
      experiences and internalizing behavior and that sex plays a moderating role.
      Behavioral EK was associated with self-reported loneliness,
      victimization/rejection, and parent-reported internalizing symptoms. Emotion
      recognition and expressive emotion knowledge were related to self-reported
      loneliness, and emotion situation knowledge was related to parent-reported
      internalizing symptoms and negative peer nominations. Sex moderated many of these
      associations, suggesting that EK may operate differently for girls versus boys in
      the preschool social context. Results are discussed with regard to the role of EK
      for social development and intervention implications.

PMID- 25859098
TI  - Oral Health Related Awareness and Practices among Pregnant Women in Bagalkot
      District, Karnataka, India.
AB  - BACKGROUND: Cumulative evidence in the dental literature strongly supports the
      fact that poor oral hygiene practices and inadequate attention toward oral health
      during pregnancy have an impact on developing the fetus and significant adverse
      postnatal effects. Available literature suggests that the research is deficit in
      assessing knowledge and practices related to exposure to radiation, use of
      medication and safe period for dental treatment during pregnancy. Assessing the
      knowledge and practices among pregnant women could be a valuable tool for policy
      makers to improve the oral health. To assess knowledge and practices of pregnant
      woman regarding oral health. MATERIALS AND METHODS: This study was a cross
      sectional survey. A total of 332 samples were selected by convenience sampling
      technique. A questionnaire containing 14 close-ended questions related to
      knowledge and practices pertaining to oral health during pregnancy along with
      sociodemographic data were used for collecting baseline information. RESULTS: The
      overall level of knowledge and practice was 27.17% and 55%, respectively.
      Majority of respondents (89.10%) were not aware that gum diseases are common
      during pregnancy. Most of them (73.07%) were not aware of safe period for
      undergoing dental treatment during pregnancy. Only 19.87% were aware that
      exposure to high dose of radiation was hazardous to their babies. Around 18.6%
      did not brush when they experienced bleeding, 35.25% cleaned their teeth using
      finger. CONCLUSION: The overall results suggest that knowledge and practices of
      pregnant women need to be greatly improved. All necessary measures should be
      taken for maintenance of oral hygiene and to avoid complications with the use of
      drugs and exposure to radiation.

PMID- 25859099
TI  - Comparative Evaluation of Fracture Resistance of Endodontically Treated Teeth
      Obturated with Resin Based Adhesive Sealers with Conventional Obturation
      Technique: An In vitro Study.
AB  - BACKGROUND: To compare fracture resistance of endodontically treated teeth
      obturated with different resin-based adhesive sealers with a conventional
      obturation technique. MATERIALS AND METHODS: A total of 60 Single canaled teeth
      were divided into five groups. The first group was taken as a negative control.
      The rest of the groups were shaped using ProFile rotary files (Dentsply
      Maillefer, Ballaigues, Switzerland). The second group was obturated with gutta
      percha and a ZOE-based sealer Endoflas FS (Sanlor Dental Products, USA). The
      third group was obturated with gutta-percha and an epoxy-based sealer AH Plus
      (Dentsply, DeTrey, Germany). The fourth group was obturated with Resilon (Pentron
      Clinical Technologies, Wallingford, CT) and RealSeal sealer (Pentron Clinical
      Technologies). The fifth group was obturated with EndoREZ points and EndoREZ
      sealer (both from Ultradent, South Jordan, UT). Roots were then embedded into
      acrylic blocks and were then fixed into a material testing system and loaded with
      a stainless steel pin with a crosshead speed of 5 mm/min until fracture. The load
      at which the specimen fractured was recorded in Newtons. RESULTS: It was found
      that forces at fracture were statistically significant for the newer resin
      systems, Resilon, and EndoREZ. CONCLUSION: It was concluded that roots obturated
      with newer resin systems (Resilon and EndoREZ) enhanced the root strength almost
      up to the level of the intact roots.

PMID- 25859100
TI  - The effect of temperature on compressive and tensile strengths of commonly used
      luting cements: an in vitro study.
AB  - BACKGROUND: The luting cements must withstand masticatory and parafunctional
      stresses in the warm and wet oral environment. Mouth temperature and the
      temperature of the ingested foods may induce thermal variation and plastic
      deformation within the cements and might affect the strength properties. The
      objectives of this study were to evaluate the effect of temperature on the
      compressive and diametral tensile strengths of two polycarboxylate, a
      conventional glass ionomer and a resin modified glass ionomer luting cements and,
      to compare the compressive strength and the diametral tensile strength of the
      selected luting cements at varying temperatures. MATERIALS AND METHODS: In this
      study, standardized specimens were prepared. The temperature of the specimens was
      regulated prior to testing them using a universal testing machine at a crosshead
      speed of 1 mm/min. Six specimens each were tested at 23 degrees C, 37 degrees C
      and 50 degrees C for both the compressive and diametral tensile strengths, for
      all the luting cements. RESULTS: All the luting cements showed a marginal
      reduction in their compressive and diametral tensile strengths at raised
      temperatures. Fuji Plus was strongest in compression, followed by Fuji I > Poly F
      > Liv Carbo. Fuji Plus had the highest diametral tensile strength values,
      followed by Poly F = Fuji I = Liv Carbo, at all temperatures. CONCLUSION: An
      increase in the temperature caused no significant reduction in the compressive
      and diametral tensile strengths of the cements evaluated. The compressive
      strength of the luting cements differed significantly from one another at all
      temperatures. The diametral tensile strength of resin modified glass ionomers
      differed considerably from the other cements, whereas there was no significant
      difference between the other cements, at all the temperatures.

PMID- 25859101
TI  - Evaluation of Glycemic Control in Type 2 Diabetes Mellitus using Cytomorphometry
      of Buccal Cells and Correlation with Glycosylated Hemoglobin.
AB  - BACKGROUND: To study cytological alterations in the exfoliated buccal cells of
      diabetic patients. To analyze the cytomorphometric findings in the smears of
      uncontrolled and controlled diabetic patients and compare it with that of normal
      healthy controls. To establish a correlation between cytomorphometric changes and
      glycosylated hemoglobin (HbA1c) in diabetics and normal controls, for evaluation
      of glycemic control. MATERIALS AND METHODS: The study was carried out in 40
      confirmed diabetic patients from a hospital out-patient diabetic ward and 20
      healthy individuals as controls (Group A: n = 20), in Chennai. Specific exclusion
      criteria were used to select the study group from a larger group of subjects.
      Based on HbA1c values, the diabetic patients were categorized into Group B =
      Controlled diabetics (n = 20) (HbA1c <7%) and Group C = Uncontrolled diabetics (n
      = 20) (HbA1c >9%). After informed consent, buccal smear was collected from
      clinically normal appearing mucosa and stained with papanicoloau (PAP) stain.
      Cytomorphometric analysis of selective PAP stained cells was done using image
      analysis software, Image Pro Plus 5.5 (Olympus) and parameters determined were
      average cytoplasmic area (CA), average nuclear area (NA) and cytoplasmic:nuclear
      (C: N) ratio for an average of 50 cells/patient. RESULTS: Comparing the average
      NA among three groups, an increase through Group A, B, C, with a maximum
      significance between Group C and A was seen. The average C: N ratio showed a
      statistically significant difference between all three groups. Significant
      correlation existed between the HbA1c values and both the C: N ratio and average
      NA in all the three groups. CONCLUSIONS: Cytomorphometric analysis of buccal
      smears using the C: N ratio alteration as a reliable criteria, may serve as yet
      another non-invasive tool for screening programs for diabetic detection. And the
      technique may possibly be used also for evaluation of glycemic control in known
      diabetics.

PMID- 25859102
TI  - A spectro photometric comparative evaluation of apical sealing ability of three
      different sealers; calcium hydroxide based, resin based and zinc oxide eugenol
      based sealers.
AB  - BACKGROUND: The aim of this study was to quantitatively analyze the amount of dye
      leakage with AH26, Sealapex and Tubliseal sealers in endodonticaly treated teeth.
      MATERIALS AND METHODS: A total of 36 extracted mandibular molar specimens were
      divided into three groups; Group I: Sealapex, Group II: Tubliseal, Group II: AH26
      with 12 samples in each group. Standard access cavity and biomechanical
      preparation was done with step back flare technique. Obturations were done using
      respective sealers in the three different groups. Then, samples were subjected to
      spectro photometric analysis using a filter of 670 nm. Spectrophotometric
      analysis was performed to quantitatively analyze the amount of dye leakage with
      all three sealers. RESULTS: Tubliseal exhibited the least microleakage. In
      comparison to Sealapex, Tubliseal showed a significant difference. Compared to
      Sealapex, AH26 showed no significant difference. Comparisons made between
      Tubliseal and AH26 showed no significant difference. CONCLUSION: In the present
      study, Tubliseal sealer showed least microleage compared with Sealapex and AH26
      sealer.

PMID- 25859103
TI  - Orthodontic cements and demineralization: an in vitro comparative scanning
      electron microscope study.
AB  - BACKGROUND: Comparison of the demineralization potential of four luting cements,
      i.e. zinc phosphate, conventional glass ionomer cement (GIC), resin-modified GIC
      and acid modified composite resin. MATERIALS AND METHODS: This study was
      conducted on 75 extracted premolar teeth, which were grouped into five, each
      group containing 15 teeth. Groups were non-banded control, teeth cemented with
      the above-mentioned cements. These were incubated at 37 degrees C for 30 days in
      sealable plastic containers, after which the teeth were debanded, cleaned and
      placed in acid gelatin solution at 37 degrees C for 4 weeks to simulate the
      cariogenic solution. Then, the teeth were sectioned and examined under scanning
      electron microscope. The depth of the carious lesions was measured using image
      analysis with Digimizer software. RESULTS: The depth of the carious lesions was
      maximum with non-banded group, followed by zinc phosphate, acid modified
      composite resin, resin-modified GIC and conventional GIC. CONCLUSIONS: Among the
      four orthodontic banding cements compared, the enamel demineralization potential
      is least with conventional GIC, followed by resin-modified GIC, acid modified
      composite resin and zinc phosphate.

PMID- 25859104
TI  - Variation in Size and Form between Left and Right Maxillary Central Incisor
      Teeth.
AB  - BACKGROUND: To compare the variation in size of left and right maxillary central
      incisors for male patients (using digital calipers of 0.01 mm accuracy). To
      compare the variation in size of left and right maxillary central incisors for
      female patients (using digital calipers of 0.01 mm accuracy). To find out the
      difference between the maxillary central incisors of men and women. Its clinical
      applicability if difference exists. MATERIALS AND METHODS: A total of 70 dental
      students of PMNM Dental College and Hospital were selected. Of 70 dental
      students, 40 male and 30 female were selected. Impressions were made for all
      subjects, using irreversible hydrocolloid (Algitex, manufacturer DPI, Batch-T
      8804) using perforated stock metal trays. The mesiodistal crown width and
      cervical width were measured for each incisor and recorded separately for left
      and right teeth. The length was measured for each incisor and recorded separately
      for left and right maxillary central incisor using digitec height caliper.
      RESULTS: The mean value of maximum crown length of maxillary left central incisor
      of male was greater in length compared with maxillary right central incisor. Mean
      value of maximum crown length for male patient right and left side was greater
      compared with maximum crown length of female patient. CONCLUSION: When compared
      the dimensions of teeth between two sex, male group shows larger values to female
      group.

PMID- 25859105
TI  - Oral manifestation in mentally challenged children.
AB  - BACKGROUND: In general, mentally challenged children have higher rates poor oral
      hygiene, gingivitis and periodontitis than the general population. An
      investigation was undertaken to assess the oral manifestations of mentally
      challenged children in Chennai, India. MATERIALS AND METHODS: The study group
      consisted of 150 children (70 Down syndrome patients and 80 cerebral palsy
      patients). Of which, 93 patients were males and 57 were females. RESULTS: Speech
      difficulty hindered the communication between the patient and the dentist.
      Mastication and swallowing difficulties were also present in few children.
      Profuse salivation was a cause for drooling of saliva down the cheeks, which was
      a constant finding in cerebral palsy children. The oral hygiene statuses of the
      patient were significantly poor. The prevalence of periodontitis was 35.7% in
      Down syndrome and 55.0% in cerebral palsy patients. Whereas, the prevalence of
      gingivitis was found to be 92.9% and 61.3% respectively. The prevalence of
      fractured maxillary anterior teeth was found to be more evident in cerebral palsy
      patients (62.9%) when compared to Down syndrome patients (0.0%). An increase in
      age shows an increase in the decayed-missing-filled teeth which is statistically
      significant. CONCLUSION: The prominent findings like flat nasal bridge (94.3%),
      hypertelorism (92.9%), high arched palate (78.6%) and fissured tongue (78.6%) in
      our study, suggest that they could be used as a reliable clinical markers to
      diagnose Down syndrome condition.

PMID- 25859106
TI  - Presence of Candida albicans in Root Canals of Teeth with Apical Periodontitis
      and Evaluation of their Possible Role in Failure of Endodontic Treatment.
AB  - BACKGROUND: Candidal organisms are commensals of the oral cavity and their
      opportunistic infection depends on the interplay of local and systemic factors.
      Endodontic treatment failure has been associated with the persistence of
      microbial flora following therapy in the root canal system, and this includes
      fungi like Candida, which are resistant to conventional root canal irrigants.
      MATERIALS AND METHODS: A total of 20 mandibular molars were included in the study
      of which 15 were primary randomized controlled trial cases, whereas 5 were
      retreatment cases. The patient's saliva, as well as the root canal flora, were
      examined for the presence of Candida organisms and further confirmed for the
      presence of Candida albicans. RESULTS: Of the 20 samples comprising the study
      group, the saliva culture revealed 11 of them to have a colony forming unit (CFU)
      >400 and 9 of the 20 canals microbiology showed CFU >400. Among the 15 first-time
      root canal treatment cases, saliva examination these revealed 8 of them to have
      CFU >400 and the canal microbiology of these showed 6 of them to have CFU >400.
      Among the retreatment cases, 3 of the 5 cases showed CFU >400 in both the saliva
      DN canal culture. CONCLUSION: Candidal contamination of the root canals could be
      the cause of endodontic treatment failure and thus emphasizes the importance of
      rubber dam isolation and the use of irrigants with antifungal properties for
      sufficient duration during treatment.

PMID- 25859107
TI  - All the mandibular incisors with double canals in a single patient: a rare case.
AB  - Single rooted tooth are considered to be the easiest for root canal treatment.
      The literature has documented cases with single rooted tooth showing more than
      single canal. Understanding of root canal morphology thus is an important aspect
      to be considered for successful endodontic treatment. The case presented here
      shows a rare entity of having double canals in all the mandibular incisors in a
      single patient. 

PMID- 25859108
TI  - Brown tumor of mandible in association with primary hyperparathyroidism: a case
      report.
AB  - Brown tumors are giant cell focal lesion that arises as a result of abnormal bone
      metabolism in patients with hyperparathyroidism (HPT). The lesions localize in
      areas of extensive bone resorption, which is replaced by fibrovascular tissue and
      giant cells with abundant deposits hemorrhage and hemosiderin. A rare case of
      brown tumor of mandible in a 22-year-old woman is reported here. This case
      emphasizes the importance of a detailed systemic investigation for all lesions in
      the maxillofacial region and also discusses the diverse presentations associated
      with primary HPT. 

PMID- 25859109
TI  - From hopeless to good prognosis: journey of a failing tooth.
AB  - Chronic periodontitis, along with associated clinical findings such as pathologic
      tooth migration, diastema, functional and aesthetic aberrations, poses an immense
      challenge to a dental professional. These findings convert clinical decision
      making into a daunting task and adversely affect the prognosis and the treatment
      plan for the presenting clinical problem. An interdisciplinary approach aimed at
      restoring functional and aesthetic needs of the affected individual within the
      limitations of such a compromised clinical scenario may be a viable alternative
      to any radical treatment causing loss of natural tooth structure such as
      extraction. This article reports the usefulness of the interdisciplinary route
      for managing an otherwise hopeless clinical situation of chronic periodontitis
      complicated with extreme mobility and pathologic tooth migration, which resulted
      in compromised function and aesthetics. 

PMID- 25859110
TI  - Rhinosporidiosis presenting as a facial swelling: a case report.
AB  - Rhinosporidiosis caused by Rhinosporidium seeberi is a fungal infection, which
      affects chiefly the mucus membranes of the nose, oropharynx, and nasopharynx, as
      well as the larynx, skin, eyes, and genital mucosa. Soil and water act as a
      reservoir for the organism. Here, we present a case of Rhinosporidiosis, which
      clinically manifested as a facial swelling indicating that fungal infections
      should also be considered as one of the differential diagnoses whenever facial
      swellings are encountered. 

PMID- 25859111
TI  - Bilateral radicular cyst in mandible: an unusual case report.
AB  - A radicular cyst is one of the furthermost everyday odontogenic cysts of the
      anterior maxilla, not regularly comprehended in youth. They are found mostly at
      the apices of the tooth (periapical cyst), lateral surface of the roots (lateral
      radicular cyst) and remains in the jaw after removal of the offending tooth
      (residual cyst). The radicular cyst has been catalogued as an inflammatory cyst,
      as an outcome to pulpal necrosis succeeding caries, with a linked periapical
      inflammatory reaction. They advance sluggishly and asymptomatic lest infected.
      Because of this they can extent to big dimensions. Many times it is perplexing to
      segregate radicular cysts from the obligatory pre-existing chronic periapical
      periodontitis lesions radiographically. Here, we present a rare case with
      bilateral radicular cyst in relation to first molar of the mandible in a 19-year
      old. Orthopantomograph showed a large unilocular radiolucency with a well-defined
      border in the periapical region of the first molar on the left side extending
      from the root of the second premolar to the mesial root of the second molar.
      Correspondingly another well-defined unilocular radiolucency with a well-defined
      border was seen on the right side of the mandible. Several treatment
      possibilities are presented for a radicular cyst such as surgical endodontic
      treatment, extraction of the transgressing tooth, enucleation with primary
      closure, and marsupialization trailed by enucleation. The patient management
      comprised surgical enucleation of cystic sac followed by rehabilitation of the
      same area. 

PMID- 25859112
TI  - Cone beam computed tomography - know its secrets.
AB  - Cone-beam computed tomography (CBCT) is an advanced imaging modality that has
      high clinical applications in the field of dentistry. CBCT proved to be a
      successful investigative modality that has been used for dental and maxillofacial
      imaging. Radiation exposure dose from CBCT is 10 times less than from
      conventional CT scans during maxillofacial exposure. Furthermore, CBCT is highly
      accurate and can provide a three-dimensional volumetric data in axial, sagittal
      and coronal planes. This article describes the basic technique, difference in
      CBCT from CT and main clinical applications of CBCT. 

PMID- 25859113
TI  - Clinical and oral implications of dengue Fever: a review.
AB  - Dengue is a viral infection with fatal potential complications. It is also called
      as break-bone fever. Worldwide dengue infection is the most common mosquito-borne
      viral disease. It is caused by vector Aedesa egypti and represents a major public
      health issue in more than 100 tropical countries. The word dengue is obtained
      from Swahili phrase Ka-dinga pepo meaning "cramplikeseizure." Dengue viral
      infections are characterized by abrupt febrile illness, but can also lead to
      significant morbidity and mortality. Hence, it requires an early and correct
      diagnosis. Gingival bleeding is the most common oral manifestation of dengue
      infection. Although oral lesions are uncommon in dengue infections and if
      manifested, may be mistaken for bleeding disorders. This review emphasizes the
      significance of oral lesions as it may be the early indicators of dengue
      hemorrhagic fever. 

PMID- 25859114
TI  - Circulating tumor cells in oral cancer.

PMID- 25859116
TI  - Medicare oversight of hospital compounding gets middling marks from inspector
      general: accreditors look closely at some practices but not at others.
AB  - Medicare oversight of hospital compounding is questioned. 

PMID- 25859115
TI  - Reduce readmissions with pharmacy programs that focus on transitions from the
      hospital to the community.
AB  - Pharmacy focus on hospital discharge cuts readmissions. 

PMID- 25859118
TI  - Pharmaceutical approval update.
AB  - Palbociclib (Ibrance) for breast cancer, secukinumab (Cosentyx) for plaque
      psoriasis, meningococcal group B vaccine (Bexsero) to help prevent meningitis,
      and lenvatinib (Lenvima) for differentiated thyroid cancer. 

PMID- 25859119
TI  - Ledipasvir/Sofosbuvir (harvoni): improving options for hepatitis C virus
      infection.
AB  - Ledipasvir/sofosbuvir (Harvoni): improving options for hepatitis C virus
      infection. 

PMID- 25859120
TI  - States try to control medicaid pharmaceutical costs: numerous, diverse cost
      pressures force myriad reform efforts.
AB  - State Medicaid programs and the managed care plans that insure most recipients
      are struggling with the costs of hepatitis C medications and other specialty
      drugs that may be only the leading edge of a wave of expensive treatments for
      common conditions. 

PMID- 25859121
TI  - Assessment of hospital pharmacy preparedness for mass casualty events.
AB  - OBJECTIVES: To assess the preparedness of hospital pharmacies in New Jersey to
      provide pharmaceutical services in mass casualty scenarios. METHODS: An
      electronic cross-sectional survey was developed to assess the general knowledge
      of available resources and attitudes toward the preparedness of the pharmacy
      department. RESULTS: Out of 60 invitations to participate, 18 surveys (30%) were
      completed. Respondents practiced at community hospitals (12, 66.6%) with no
      trauma center designation (11, 67.4%) that served more than 500 licensed beds
      (five, 29.4%). Six respondents (35.3%) indicated that 75,000 to 100,000 patients
      visited their emergency departments annually. Seventeen sites (94.4%) reported
      the existence of an institutional disaster preparedness protocol; 10 (55.5%)
      indicated that there is a specific plan for the pharmacy department. Most
      respondents (10, 55.5%) were unsure whether their hospitals had an adequate
      supply of analgesics, rapid sequence intubation agents, vasopressors,
      antiemetics, respiratory medications, ophthalmics, oral antimicrobials, and
      chemical-weapon-specific antidotes. Five (27.7%) agreed that the pharmacy
      disaster plan included processes to ensure care for patients already
      hospitalized, and four (22.2%) agreed that the quantity of medication was
      adequate to treat patients and hospital employees if necessary. Medication stock
      and quantities were determined based on national or international guidelines at
      three (16.6%) institutions surveyed. CONCLUSION: This survey demonstrates a lack
      of general consensus regarding hospital pharmacy preparedness for mass casualty
      scenarios despite individualized institutional protocols for disaster
      preparedness. Standardized recommendations from government and/or professional
      pharmacy organizations should be developed to guide the preparation of hospital
      pharmacy departments for mass casualty scenarios.

PMID- 25859122
TI  - Kenneth tanabe works to solve the mysteries of liver cancer: while progress has
      been relatively slow, this noted expert sees reasons for hope.
AB  - Dr. Tanabe, Chief of the Division of Surgical Oncology at Massachusetts General
      Hospital, studies preventing and treating hepatocellular carcinoma, the most
      rapidly rising cause of cancer-related mortality. Promising developments are on
      the horizon. 

PMID- 25859123
TI  - The antibiotic resistance crisis: part 1: causes and threats.
AB  - Decades after the first patients were treated with antibiotics, bacterial
      infections have again become a threat because of the rapid emergence of resistant
      bacteria-a crisis attributed to abuse of these medications and a lack of new drug
      development. 

PMID- 25859124
TI  - Pharmacotherapy of neuropsychiatric symptoms of dementia.
AB  - Approximately 5 million Americans have dementia, and many receive psychiatric
      medications. Management of such patients is complex and controversial, and it has
      become apparent that all potential pharmacological therapies present risks. 

PMID- 25859125
TI  - Cautious optimism for growth in Alzheimer's disease treatments.
AB  - Available options for Alzheimer's disease are used only for symptomatic
      improvement, but disease-modifying therapies may help triple annual medication
      sales by 2023. 

PMID- 25859126
TI  - First records of the jewel beetles Chrysobothrisdesmaresti (Laporte & Gory, 1836)
      and Hiperanthastempelmanni Berg, 1889 (Coleoptera: Buprestidae) in Bolivia.
AB  - The jewel beetle species Chrysobothrisdesmaresti (Laporte & Gory, 1836) and
      Hiperanthastempelmanni Berg, 1889, have been recorded in Bolivia for the first
      time. Both species were collected on xeric Acacia trees. As indicated by their
      presence on Acacia and previous records, both species may be endemic to the arid
      intermountain valleys of the Southern Bolivian and Northern Argentinean Andes as
      well as the Chaco lowland forests. 

PMID- 25859127
TI  - Fauna Europaea: Hymenoptera - Apocrita (excl. Ichneumonoidea).
AB  - Fauna Europaea provides a public web-service with an index of scientific names
      (including important synonyms) of all living European land and freshwater
      animals, their geographical distribution at country level (up to the Urals,
      excluding the Caucasus region), and some additional information. The Fauna
      Europaea project covers about 230,000 taxonomic names, including 130,000 accepted
      species and 14,000 accepted subspecies. This represents a huge effort by more
      than 400 contributing specialists throughout Europe and is a unique (standard)
      reference suitable for many users in science, government, industry, nature
      conservation and education. Hymenoptera is one of the four largest orders of
      insects, with about 130,000 described species. In the Fauna Europaea database,
      'Hymenoptera - Apocrita (excluding Ichneumonoidea)' comprises 13 superfamilies,
      52 families, 91 subfamilies, 38 tribes and 13,211 species. The paper includes a
      complete list of taxa dealt with, the number of species in each and the name of
      the specialist responsible for data acquisition. As a general conclusion about
      the European fauna of Hymenoptera, the best known countries in terms of recorded
      species are those from northwestern Europe, with the least known fauna probably
      in the more eastern and southeastern parts of Europe. 

PMID- 25859128
TI  - Extravagant female sexual display in a Megaselia Rondani species (Diptera:
      Phoridae).
AB  - The behavior of females of a species of Megaselia is described. Females perch on
      leaves and occasionally "dance", fluttering their wings while rapidly running on
      the leaf surface. During this dance, they evert bright white abdominal sacs that
      apparently constitute part of a visual display to attract males. The evolutionary
      basis of these behaviors is discussed. 

PMID- 25859129
TI  - Taxonomy and distribution of the ant Cataglyphissetipes (Hymenoptera:
      Formicidae).
AB  - Taxonomy and distribution of the ant species Cataglyphissetipes (Forel, 1894) is
      herewith detailed. C.setipes is redescribed, based on workers, queens, and males.
      Photomontage images of all castes are provided. Information on the distribution
      and ecology of this species is also given. A key to the Indian species of
      Cataglyphis is presented. 

PMID- 25859130
TI  - Seven new species of Spathidexia Townsend (Diptera: Tachinidae) reared from
      caterpillars in Area de Conservacion Guanacaste, Costa Rica.
AB  - We describe seven new species of Spathidexia (Diptera: Tachinidae) reared from
      Area de Conservacion Guanacaste (ACG), northwestern Costa Rica. All were reared
      from -various species of ACG caterpillars during an ongoing inventory of
      caterpillars, their food plants and their parasitoids. By coupling morphology,
      photographic documentation, life history and molecular data, we provide a clear
      and concise description of each species. All are known to be previously
      undescribed as a result of a comprehensive study of the genus by DMW.
      Spathidexiaatripalpus sp. n., Spathidexiajuanvialesi sp. n.,
      Spathidexiamarioburgosi sp. n., Spathidexialuisrobertogallegosi sp. n.,
      Spathidexialuteola sp. n., Spathidexiahernanrodriguezi sp. n. and
      Spathidexiaaurantiaca sp. n. are all authored and described by Fleming and Wood.
      Minthodexiopsis Townsend is proposed by Wood as a new synonym of Spathidexia. A
      new combination proposed by Wood as a result of the new synonymy is S.flavicornis
      (Brauer & Bergenstamm) comb. n. 

PMID- 25859131
TI  - Notes on Shore Flies (Diptera: Ephydridae) from Finland and north-western Russia.
AB  - The recent checklist of the Ephydridae of Finland by Zatwarnicki and Kahanpaa
      (2014) mentioned 13 ephydrid species as new for Finland without further details.
      This paper presents detailed records for those species and a few other species of
      interest. Four species are recorded for the first time from Russia.
      Trimerinaindistincta Krivosheina, 2004 is herein considered as a new junior
      synonym of Trimerinamicrochaeta Hendel, 1932, syn. nov. 

PMID- 25859132
TI  - Bridging the distributional gap of Tyloridastriata (Thorell, 1877) and new
      synonymy (Araneae: Tetragnathidae).
AB  - BACKGROUND: Although Tyloridastriata has not been reported from India,
      observations on India Biodiversity Portal (IBP 2015), an open access repository
      for biodiversity information of Indian subcontinent, showed images resembling
      this species. The respective locality in Gujarat, India was explored and
      specimens were studied to confirm record of T.striata in India. Literature study
      showed some taxonomic lacunae which needed to be resolved. NEW INFORMATION: The
      tetragnathid spider Tyloridastriata (Thorell, 1877) is redescribed on examination
      of its long unknown syntypes from Kendari, Southeast Sulawesi deposited in the
      Natural History Museum of Giacomo Doria, Genoa, Italy and additional material
      from Kendari and other Indonesian regions. Description of Tyloridastellimicans
      (Simon, 1885) mentions its identity with T.striata, which however characterizes
      sub-adult of T.striata and is accordingly synonymized. Tyloridastriata is newly
      recorded from India which links the distributional gap between China to Australia
      and Comoros Islands. Distributional and taxonomic records of Tylorida species
      with T.striata- like globose abdomen infer probable synonymy, which is subject to
      genus revision.

PMID- 25859133
TI  - Highlights in neuro-ophthalmology.

PMID- 25859134
TI  - Cerebral venous sinus stenting for pseudotumor cerebri: A review.
AB  - Pseudotumor cerebri is characterized by headaches, visual field changes,
      papilledema and an elevated cerebrospinal fluid opening pressure without evidence
      of an intracranial mass. In the setting of failed medical therapy, surgical
      options such as ventriculoperitoneal shunts and optic nerve sheath fenestrations
      are considered. Recently, venous sinus stenting has emerged as a new treatment
      option for patients with pseudotumor cerebri. We review the role of cerebral
      venous sinus stenting in the management of patients with medically refractory
      pseudotumor cerebri. Although long- term studies are needed in this field, the
      current reports indicate a favorable outcome for preventing vision loss and
      symptom control. 

PMID- 25859135
TI  - OCT: New perspectives in neuro-ophthalmology.
AB  - Optical coherence tomography (OCT) has become essential to evaluate
      axonal/neuronal integrity, to assess disease progression in the afferent visual
      pathway and to predict visual recovery after surgery in compressive optic
      neuropathies. Besides that OCT testing is considered a powerful biomarker of
      neurodegeneration and a promising outcome measure for neuroprotective trials in
      multiple sclerosis (MS). Currently, spectral-domain OCT (SD-OCT) technology
      allows quantification of retinal individual layers. The Ganglion Cell layer (GCL)
      investigation has become one of the most useful tools from a neuro-ophthalmic
      perspective. It has a high correlation with perimetry, is predictive of future
      progression and is a highly sensitive, specific of several neuro-ophthalmic
      pathologies. Moreover the superior correlation with clinical measures compared to
      peripapillary retinal nerve fiber layer (pRNFL) suggests that GCL analysis might
      be a better approach to examine MS neurodegeneration. In disorders with optic
      disk edema, such as ischemic optic neuropathy, papillitis and papilledema,
      reduction in RNFL thickness caused by axonal atrophy is difficult to distinguish
      from a swelling resolution. In this setting, and in buried optic nerve head
      drusen (ONHD), GCL analysis may provide more accurate information than RNFL
      analysis and it might be an early structural indicator of irreversible neuronal
      loss. Enhanced depth imaging OCT (EDI-OCT) provides in vivo detail of ONHD,
      allowing to evaluate and quantify the drusen dimensions. OCT is improving our
      knowledge in hereditary optic neuropathies. Furthermore, there is growing
      evidence about the role of OCT as an adjunctive biomarker of disorders such as
      Alzheimer and Parkinson's disease. 

PMID- 25859136
TI  - Idiopathic intracranial hypertension in the Middle East: A growing concern.
AB  - Idiopathic Intracranial Hypertension (IIH) is a disorder of increased
      intracranial pressure without any identifiable etiology. It is defined by
      elevated intracranial pressure (ICP) with normal neuroimaging and normal
      cerebrospinal fluid (CSF) contents. IIH typically affects young obese women and
      produces symptoms and signs related to high ICP. Headache and blurred vision are
      the most common symptoms, and papilledema is the major clinical sign. In this
      review we examine the epidemiology and demographic features of IIH in Middle
      Eastern countries and compare and contrast them with the published IIH literature
      from Western countries. The incidence of IIH in several Middle East countries has
      been estimated at 2.02-2.2/100,000 in the general population, which is higher
      than the Western rate. Obesity is a major risk factor globally and it is
      associated with an increased risk of severe vision loss due to IIH. There has
      been an increase in obesity prevalence in the Middle East countries mainly
      affecting the Gulf Council Countries (GCC), which parallels increased industrial
      development. This rise may be contributing to the increasing incidence of IIH in
      these countries. Other risk factors may also be contributing to IIH in Middle
      East countries and the differences and similarities to Western IIH merit further
      study. 

PMID- 25859137
TI  - Congenital anomalies of the optic nerve.
AB  - Congenital optic nerve head anomalies are a group of structural malformations of
      the optic nerve head and surrounding tissues, which may cause congenital visual
      impairment and blindness. Each entity in this group of optic nerve anomalies has
      individually become more prevalent as our ability to differentiate between them
      has improved due to better characterization of cases. Access to better medical
      technology (e.g., neuroimaging and genetic analysis advances in recent years) has
      helped to expand our knowledge of these abnormalities. However, visual impairment
      may not be the only problem in these patients, some of these entities will be
      related to ophthalmologic, neurologic and systemic features that will help the
      physician to identify and predict possible outcomes in these patients, which
      sometimes may be life-threatening. Herein we present helpful hints, associations
      and management (when plausible) for them. 

PMID- 25859138
TI  - Neuro-ophthalmological approach to facial nerve palsy.
AB  - Facial nerve palsy is associated with significant morbidity and can have
      different etiologies. The most common causes are Bell's palsy, Ramsay-Hunt
      syndrome and trauma, including surgical trauma. Incidence varies between 17 and
      35 cases per 100,000. Initial evaluation should include accurate clinical
      history, followed by a comprehensive investigation of the head and neck,
      including ophthalmological, otological, oral and neurological examination, to
      exclude secondary causes. Routine laboratory testing and diagnostic imaging is
      not indicated in patients with new-onset Bell's palsy, but should be performed in
      patients with risk factors, atypical cases or in any case without resolution
      within 4 months. Many factors are involved in determining the appropriate
      treatment of these patients: the underlying cause, expected duration of nerve
      dysfunction, anatomical manifestations, severity of symptoms and objective
      clinical findings. Systemic steroids should be offered to patients with new-onset
      Bell's palsy to increase the chance of facial nerve recovery and reduce
      synkinesis. Ophthalmologists play a pivotal role in the multidisciplinary team
      involved in the evaluation and rehabilitation of these patients. In the acute
      phase, the main priority should be to ensure adequate corneal protection.
      Treatment depends on the degree of nerve lesion and on the risk of the corneal
      damage based on the amount of lagophthalmos, the quality of Bell's phenomenon,
      the presence or absence of corneal sensitivity and the degree of lid retraction.
      The main therapy is intensive lubrication. Other treatments include: taping the
      eyelid overnight, botulinum toxin injection, tarsorrhaphy, eyelid weight
      implants, scleral contact lenses and palpebral spring. Once the cornea is
      protected, longer term planning for eyelid and facial rehabilitation may take
      place. Spontaneous complete recovery of Bell's palsy occurs in up to 70% of
      cases. Long-term complications include aberrant regeneration with synkinesis. FNP
      after acoustic neuroma surgery remains the most common indication for FN
      rehabilitation. 

PMID- 25859139
TI  - Review of Giant cell arteritis.
AB  - Giant-cell arteritis (GCA) is a systemic autoimmune disease affecting primarily
      the elderly. Giant cell arteritis can cause sudden and potentially bilateral
      sequential vision loss in the elderly. Therefore, it is considered a medical
      emergency in ophthalmology and a significant cause of morbidity in an
      increasingly aging population. Ophthalmologists need to be able to recognize the
      classic symptoms and signs of this disease, and then be able to work-up and treat
      these patients in an efficient manner. An in-depth review of GCA from the
      literature as well as personal clinical experience follows. 

PMID- 25859140
TI  - IgG4-related ophthalmic disease.
AB  - IgG4-related disease is a fibro-inflammatory condition with tendency to form
      tumors with inflammatory infiltrate with IgG4 rich plasma cells and elevation of
      IgG4 level in serum, which may affect virtually every organ and tissue in the
      organism. IgG4-related ophthalmic disease may present as dacryoadenitis,
      myositis, other orbital tissues, hypophysitis or pachymeningitis causing cranial
      neuropathies. The diagnosis of IgG4-related disease is based on a typical
      clinical scenario, supportive laboratory data, expected radiological
      characteristics and distinct histopathological and immunohistochemical features.
      Corticosteroid followed by the use of long-term immunosuppressive therapy is the
      most commonly attempted treatment. 

PMID- 25859141
TI  - Intracranial pressure and skull remodeling.
AB  - In this article we review bony changes resulting from alterations in intracranial
      pressure (ICP) and the implications for ophthalmologists and the patients for
      whom we care. Before addressing ophthalmic implications, we will begin with a
      brief overview of bone remodeling. Bony changes seen with chronic intracranial
      hypotension and hypertension will be discussed. The primary objective of this
      review was to bring attention to bony changes seen with chronic intracranial
      hypotension. Intracranial hypotension skull remodeling can result in
      enophthalmos. In advanced disease enophthalmos develops to a degree that is truly
      disfiguring. The most common finding for which subjects are referred is ocular
      surface disease, related to loss of contact between the eyelids and the cornea.
      Other abnormalities seen include abnormal ocular motility and optic atrophy.
      Recognition of such changes is important to allow for diagnosis and treatment
      prior to advanced clinical deterioration. Routine radiographic assessment of bony
      changes may allow for the identification of patient with abnormal ICP prior to
      the development of clinically significant disease. 

PMID- 25859142
TI  - Sixth nerve palsy + ipsilateral Horner's Syndrome = Parkinson's Syndrome.
AB  - PURPOSE: To present five patients with VIth nerve palsy and ipsilateral Horner's
      Syndrome (HS), as a result of cavernous sinus alteration. STUDY DESIGN:
      Consecutive case series. MATERIAL AND METHODS: Five patients presented abducens
      palsy with horizontal diplopia (3 in primary position and 2 in lateral gaze only)
      and ipsilateral HS. Apraclonidine 0.5% drops evidenced sympathetic denervation in
      all patients 40-60 min after instillation. All 5 cases had neuroimages (MRI in 3
      cases, Computerized Tomography - CT in one case and Magnetic Resonance
      Angiography - MRA in one case) demonstrating cavernous sinus lesions; 2
      meningiomas, 1 carotid-cavernous aneurism, 1 foreign body (bullet) and 1 squamous
      cell carcinoma. CONCLUSION: Lesions on the cavernous sinus need to be considered
      in cases of abducens nerve palsy and ipsilateral Horner's Syndrome.

PMID- 25859143
TI  - Peripapillary nerve fiber layer thickness changes after macular photocoagulation
      for clinically significant diabetic macular edema.
AB  - PURPOSE: To evaluate the effect of macular photocoagulation (MPC) on
      peripapillary nerve fiber layer (PNFL) thickness measurement in patients with
      clinically significant diabetic macular edema (CSME). METHODS: This study was a
      prospective interventional case series. Patients with CSME underwent MPC. Optical
      coherence tomography (OCT) was used to measure the PNFL and central macular
      thicknesses before and 3 months after MPC. RESULTS: Thirty-three eyes of 25
      patients with a mean age of 59.4 +/- 7.2 years were included. There was no
      statistically significant difference between pre- and post-MPC mean best
      corrected visual acuity (0.35 +/- 0.29 and 0.40 +/- 0.23 LogMAR, respectively, P
      = 0.2). Mean baseline and 3 months central macular subfield thickness was 305.9
      +/- 90.7 and 317.5 +/- 112.4 microns, respectively (P = 0.1). Peripapillary nerve
      fiber layer thickness was 105.7 +/- 10.0 before and 106.1 +/- 9.9 three months
      after MPC (P = 0.7). No significant differences were found between pre and post
      MPC measurements in temporal, nasal, inferior and superior nerve fiber layer
      thickness in each quadrant around optic nerve head (P > 0.05). CONCLUSIONS:
      Macular photocoagulation has no statistically significant effect on PNFL
      thickness measurements in patients with CSME.

PMID- 25859144
TI  - Macular star formation in diabetic patients with non-arteritic anterior ischemic
      optic neuropathy (NA-AION).
AB  - BACKGROUND: NA-AION is a condition that exhibits a number of unique
      characteristics in diabetics compared with the rest of the population. In some
      diabetic patients with NA-AION, lipid deposits can be observed around the macula
      forming an incomplete macular star. METHODS: We describe 12 case studies of
      patients with NA-AION observing the development of lipid deposits around the
      macula forming an incomplete macular star. RESULTS: All our patients developed
      some level of lipid deposits around the macula in the form of a macular hemistar
      in the course of their illness. CONCLUSION: Some authors have suggested that the
      macular star is formed by transudation from capillaries deep in the optic disk
      through the intermediary tissue of Kuhnt, which is located between the retina and
      the anterior portion of the lamina retinalis. However, the development of the
      macular star is currently understood not as a simple transudation but as a
      multifactorial process involving the presence of vascular damage around the optic
      disk, which is considered one of the most important factors leading to its
      occurrence. Although some studies mention the presence of a macular star in
      patients with NA-AION, we believe that this phenomenon may be significantly more
      common than the current literature suggests.

PMID- 25859145
TI  - Correlation of visual field defects and optical coherence tomography finding in
      migraine patients.
AB  - AIM OF WORK: The aim of our work was to detect any structural or functional
      visual defects during and in between the attacks in patients with migraine.
      PATIENT AND METHODS: Sixty patients with migraine as well as sixty age and sex
      matched controls were included. All cases were subjected to full ophthalmological
      examination. Cases with any previously known optic nerve abnormalities or with
      history of increased intraocular pressure were excluded from this study. A full
      threshold 24-2 automated perimetry as well as optical coherence tomography (OCT)
      were performed for retinal nerve fiber layer (RNFL) thickness. Correlations
      between results of study group with migraine and controls were analyzed and
      recorded. RESULTS: There was a statistically significant difference between the
      patients with migraine and the controls in visual field analysis which was (P <
      0.05) for generalized visual field deficits and (P < 0.001) for localized visual
      field deficits during the attack with no statistically significant difference in
      visual field in between the attacks (P > 0.05). OCT RNFL thickness had no
      statistically significant difference between migraine and control groups (P >
      0.05). CONCLUSION: Migraine can cause functional ocular disorder without any
      structural abnormalities.

PMID- 25859146
TI  - Behcet's disease presenting as intracranial hypertension due to cerebral venous
      thrombosis.
AB  - The non-parenchymal central nervous system's (CNS) involvement in Behcet's
      disease (BD) is considered rare. We herein report a case of BD complicated by
      intracranial hypertension (ICH) due to cerebral venous thrombosis (CVT) in a 25
      year-old Saudi male. Our patient presented with a four-week history of
      increasingly severe headache, nausea and diplopia, which were preceded by
      previous recurrent intermittent oral and genital ulcers, history suggestive of
      acneiform lesions and arthralgia over the past two years. Ophthalmic examination
      disclosed normal visual acuity (20/20) in both eyes with bilateral 6th nerve
      palsy and papilledema. Both eyes showed no signs of anterior or posterior segment
      inflammation. Oral and genital ulcers were found on physical examination with no
      other lesions. Magnetic resonance imaging (MRI) and magnetic resonance venography
      (MRV) of the brain showed lack of flow in the right transverse and sigmoid dural
      sinuses suggestive of venous thrombosis. On lumbar puncture, the opening pressure
      was greatly raised. After a comprehensive screening for prothrombotic conditions,
      a diagnosis of BD with ICH due to CVT was made. The patient was then treated by
      oral prednisolone, azathioprine, colchicine, cyclosporine, as well as
      anticoagulation, which resulted in significant clinical improvement. 

PMID- 25859147
TI  - Myelinated retinal nerve fibers (MRNF) - Dilemmas related to their influence on
      visual function.
AB  - Myelinated nerve fibers (MNF) occur in less than 1% of the population, however,
      they might be responsible for diagnostic dilemmas in cases with visual loss. The
      case report of an aged pseudophakic patient with visual deterioration in the
      right eye and MNF in both eyes is presented. The documentation provided by the
      patient proved recent several examinations of both fundi, and all of them were
      described as normal. Physical examination revealed the posterior capsule
      opacification in the right eye, white lesions on the retina of the right eye
      around the optic disk, and in the left eye - the peripheral, which could
      correspond to the myelinated fibers. Although visual field changes and OCTs
      corresponded to the NMF, it turned out, however, that visual acuity loss was in
      fact caused by PCO and was reversed by the YAG capsulotomy procedure. This case
      shows some problems related to MNF diagnosis and evaluation of their influence on
      visual function. 

PMID- 25859148
TI  - Nanophthalmos and hemiretinal vein occlusion: A case report.
AB  - Many risk factors have been linked to retinal vein occlusions (RVOs) whether
      central or branch retinal vein occlusion. Ocular risk factors include glaucoma
      and hypermetropia. Controversy exists to whether short axial length is a risk
      factor for retinal vein occlusions. We report an extreme case that supports the
      latter hypothesis. A 33-year-old male presented with decreased visual acuity in
      the left eye. He turned out to have nanophthalmos with hemiretinal vein occlusion
      and macular edema with unremarkable systemic work up for retinal vein occlusion
      except for a glycated hemoglobin (HbA1c) level of 7%. To our knowledge this is
      the first case report of hemiretinal vein occlusion in the setting of
      nanophthalmos and suggests that short axial length may be a risk factor for
      retinal vein occlusion. 

PMID- 25859149
TI  - A systematic review of methodology: time series regression analysis for
      environmental factors and infectious diseases.
AB  - BACKGROUND: Time series analysis is suitable for investigations of relatively
      direct and short-term effects of exposures on outcomes. In environmental
      epidemiology studies, this method has been one of the standard approaches to
      assess impacts of environmental factors on acute non-infectious diseases (e.g.
      cardiovascular deaths), with conventionally generalized linear or additive models
      (GLM and GAM). However, the same analysis practices are often observed with
      infectious diseases despite of the substantial differences from non-infectious
      diseases that may result in analytical challenges. METHODS: Following the
      Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines,
      systematic review was conducted to elucidate important issues in assessing the
      associations between environmental factors and infectious diseases using time
      series analysis with GLM and GAM. Published studies on the associations between
      weather factors and malaria, cholera, dengue, and influenza were targeted.
      FINDINGS: Our review raised issues regarding the estimation of susceptible
      population and exposure lag times, the adequacy of seasonal adjustments, the
      presence of strong autocorrelations, and the lack of a smaller observation time
      unit of outcomes (i.e. daily data). These concerns may be attributable to
      features specific to infectious diseases, such as transmission among individuals
      and complicated causal mechanisms. CONCLUSION: The consequence of not taking
      adequate measures to address these issues is distortion of the appropriate risk
      quantifications of exposures factors. Future studies should pay careful attention
      to details and examine alternative models or methods that improve studies using
      time series regression analysis for environmental determinants of infectious
      diseases.

PMID- 25859150
TI  - Molecular Epidemiology of Dengue Viruses Co-circulating in Upper Myanmar in 2006.
AB  - To understand the molecular epidemiology of circulating dengue viruses (DENV) in
      Upper Myanmar, DENV isolation was attempted by inoculating the sera of a panel of
      110 serum samples onto a C6/36 mosquito cell line. The samples were collected
      from dengue (DEN) patients admitted at Mandalay Children's Hospital in 2006.
      Infected culture fluids were subjected to a RT-PCR to detect the DENV genome.
      Three DENV strains were isolated. This was the first DENV isolation performed
      either in Mandalay or in Upper Myanmar. One strain belonged to DENV serotype-3
      (DENV-3), and two other strains belonged to DENV serotype-4 (DEN-4). The sequence
      data for the envelope gene of these strains were used in a phylogenetic
      comparison of DENV-3 and DENV-4 from various countries. Phylogenetic analyses
      revealed that this DENV-3 strain was clustered within genotype II, and the two
      DENV-4 strains were clustered within genotype I in each serotype. The Myanmar
      strains were closely related to strains from the neighboring countries of
      Thailand and Bangladesh. These results are important for elucidating the trends
      of recent and future DEN outbreaks in Myanmar. 

PMID- 25859151
TI  - Assessment of Climate-sensitive Infectious Diseases in the Federated States of
      Micronesia.
AB  - BACKGROUND: The health impacts of climate change are an issue of growing concern
      in the Pacific region. Prior to 2010, no formal, structured, evidence-based
      approach had been used to identify the most significant health risks posed by
      climate change in Pacific island countries. During 2010 and 2011, the World
      Health Organization supported the Federated States of Micronesia (FSM) in
      performing a climate change and health vulnerability and adaptation assessment.
      This paper summarizes the priority climate-sensitive health risks in FSM, with a
      focus on diarrheal disease, its link with climatic variables and the implications
      of climate change. METHODS: The vulnerability and adaptation assessment process
      included a review of the literature, extensive stakeholder consultations, ranking
      of climate-sensitive health risks, and analysis of the available long-term data
      on climate and climate-sensitive infectious diseases in FSM, which involved
      examination of health information data from the four state hospitals in FSM
      between 2000 and 2010; along with each state's rainfall, temperature and El Nino
      Southern Oscillation data. Generalized linear Poisson regression models were used
      to demonstrate associations between monthly climate variables and cases of
      climate-sensitive diseases at differing temporal lags. RESULTS: Infectious
      diseases were among the highest priority climate-sensitive health risks
      identified in FSM, particularly diarrheal diseases, vector-borne diseases and
      leptospirosis. Correlation with climate data demonstrated significant
      associations between monthly maximum temperature and monthly outpatient cases of
      diarrheal disease in Pohnpei and Kosrae at a lag of one month and 0 to 3 months,
      respectively; no such associations were observed in Chuuk or Yap. Significant
      correlations between disease incidence and El Nino-Southern Oscillation cycles
      were demonstrated in Kosrae state. CONCLUSIONS: Analysis of the available data
      demonstrated significant associations between climate variables and climate
      sensitive infectious diseases. This information should prove useful in
      implementing health system and community adaptation strategies to avoid the most
      serious impacts of climate change on health in FSM.

PMID- 25859152
TI  - The role of carbohydrates in infection strategies of enteric pathogens.
AB  - Enteric pathogens cause considerable public health concerns worldwide including
      tropical regions. Here, we review the roles of carbohydrates in the infection
      strategies of various enteric pathogens including viruses, bacteria and protozoa,
      which infect the epithelial lining of the human and animal intestine. At host
      cell entry, enteric viruses, including norovirus, recognize mainly histo-blood
      group antigens. At the initial step of bacterial infections, carbohydrates also
      function as receptors for attachment. Here, we describe the function of
      carbohydrates in infection by Salmonella enterica and several bacterial species
      that produce a variety of fimbrial adhesions. During invasion by enteropathogenic
      protozoa, apicomplexan parasites utilize sialic acids or sulfated glycans.
      Carbohydrates serve as receptors for infection by these microbes; however, their
      usage of carbohydrates varies depending on the microbe. On the surface of the
      mucosal tissues of the gastrointestinal tract, various carbohydrate moieties are
      present and play a crucial role in infection, representing the site of infection
      or route of access for most microbes. During the infection and/or invasion
      process of the microbes, carbohydrates function as receptors for various
      microbes, but they can also function as a barrier to infection. One approach to
      develop effective prophylactic and therapeutic antimicrobial agents is to modify
      the drug structure. Another approach is to modify the mode of inhibition of
      infection depending on the individual pathogen by using and mimicking the
      interactions with carbohydrates. In addition, similarities in mode of infection
      may also be utilized. Our findings will be useful in the development of new drugs
      for the treatment of enteric pathogens. 

PMID- 25859153
TI  - Visualization of Malaria Parasites in the Skin Using the Luciferase Transgenic
      Parasite, Plasmodium berghei.
AB  - We produced a transgenic rodent malaria parasite (Plasmodium berghei) that
      contained the luciferase gene under a promoter region of elongation factor
      1alpha. These transgenic (TG) parasites expressed luciferase in all stages of
      their life cycle, as previously reported. However, we were the first to succeed
      in observing sporozoites as a mass in mouse skin following their deposition by
      the probing of infective mosquitoes. Our transgenic parasites may have emitted
      stronger bioluminescence than previous TG parasites. The estimated number of
      injected sporozoites by mosquitoes was between 34 and 775 (median 80). Since
      luciferase activity diminished immediately after the death of the parasites,
      luciferase activity could be an indicator of the existence of live parasites. Our
      results indicated that sporozoites survived at the probed site for more than 42
      hours. We also detected sporozoites in the liver within 15 min of the intravenous
      injection. Bioluminescence was not observed in the lung, kidney or spleen. We
      confirmed the observation that the liver was the first organ in which malaria
      parasites entered and increased in number. 

PMID- 25859154
TI  - A Prospective Hospital-based Surveillance to Estimate Rotavirus Disease Burden in
      Bhutanese Children under 5 Years of Age.
AB  - As part of efforts to develop an informed policy for rotavirus vaccination, this
      prospective study was conducted to estimate the burden of rotavirus diarrhea
      among children less than 5 years old attended to the Department of Pediatrics,
      Jigme Dorji Wangchuk National Referral Hospital (JDWNRH), Thimphu, Bhutan. The
      duration of the study was three years, extending from February 2010 through
      December 2012. We estimated the frequency of hospitalization in the pediatric
      ward and dehydration treatment unit (DTU) for diarrhea and the number of events
      attributable to rotavirus infection among children under 5 years of age. During
      the study period, a total of 284 children (1 in 45) were hospitalized in the
      pediatric ward, and 2,220 (1 in 6) in the DTU with diarrhea among children
      residing in the Thimphu district. Group A rotavirus was detected in 32.5% and
      18.8% of the stool samples from children hospitalized in the pediatric ward,
      respectively. Overall, 22.3% of the stool samples were rotavirus-positive, and
      the majority (90.8%) of them was detected in children under 2 years of age. From
      this study, we estimated that the annual incidence of hospitalization in the
      pediatric ward and DTU due to rotavirus diarrhea was 2.4/1000 (95% CI 1.7-3.4)
      and 10.8/1000 (95% CI 9.1-12.7) children, respectively. This study revealed that
      rotavirus is a major cause of diarrhea in Bhutanese children in Thimphu district
      and since no study has been performed previously, represents an important finding
      for policy discussions regarding the adoption of a rotavirus vaccine in Bhutan. 

PMID- 25859155
TI  - Acute scrotal ulcers in typhoid Fever: case report and literature review.
AB  - BACKGROUND: In developed countries, typhoid fever is a travel-associated disease
      that is often overlooked. However, as standard blood and stool culture methods
      have relatively low sensitivity, diagnosis depends heavily on clinical signs and
      symptoms and on a high level of suspicion. METHODS: Reported here is the case of
      an 18-year-old male who presented with fever and acute scrotal ulcers and whose
      blood cultures were positive for Salmonella enterica serotype Typhi. A review of
      genital ulcers associated with typhoid fever in the literature is discussed.
      CONCLUSION: This report suggests that typhoid fever is a differential diagnosis
      of acute genital ulcers.

PMID- 25859156
TI  - Survey of wild mammal hosts of cutaneous leishmaniasis parasites in panama and
      costa rica.
AB  - The eco-epidemiology of American cutaneous leishmaniasis (ACL) is driven by
      animal reservoir species that are a source of infection for sand flies that serve
      as vectors infecting humans with Leishmania spp parasites. The emergence and re
      emergence of this disease across Latin America calls for further studies to
      identify reservoir species associated with enzootic transmission. Here, we
      present results from a survey of 52 individuals from 13 wild mammal species at
      endemic sites in Costa Rica and Panama where ACL mammal hosts have not been
      previously studied. For Leishmania spp. diagnostics we employed a novel PCR
      technique using blood samples collected on filter paper. We only found Leishmania
      spp parasites in one host, the two-toed sloth, Choloepus hoffmanni. Our findings
      add further support to the role of two-toed sloths as an important ACL reservoir
      in Central America. 

PMID- 25859157
TI  - Hospitalizations of cancer patients in the last month of life: quality indicator
      scores reveal large variation between four European countries in a mortality
      follow-back study.
AB  - BACKGROUND: Repeated and long hospitalizations of cancer patients at the end of
      life have been suggested as indicators of low quality of palliative care.
      Comparing the care delivered between different countries with the help of these
      quality indicators may identify opportunities to improve practice. Our objective
      is twofold: firstly, to describe the scores for the existing quality indicators
      "the percentage of time spent in hospital" and "the proportion of adult patients
      with more than one hospitalization in the last 30 days of life" in populations of
      cancer patients in four European countries and to see whether these countries met
      previously defined performance standards; secondly, to assess whether these
      scores are related to receiving palliative care from their GP. METHODS: A
      mortality follow-back study was conducted, based on data recorded by
      representative GP networks for samples of cancer patients living at home who died
      non-suddenly in Belgium (n = 500), the Netherlands (n = 310), Italy (n = 764),
      and Spain (n = 224). RESULTS: The quality indicator score for "the percentage of
      time spent in hospital" in the last month of life was 14.1% in the Netherlands,
      17.7% in Spain, 22.2% in Italy, and 24.6% in Belgium, which means that none of
      the countries met the performance standard of <10%. For the "proportion of
      patients with more than one hospitalization in the last 30 days of life", two
      countries met the performance standard of <4%: the Netherlands (0.6%) and Italy
      (3.1%). Spain had a score of 4.0% and Belgium scored 5.4%. When patients received
      palliative care from their GP, significantly less time was spent in hospital in
      the last month and fewer hospitalizations took place. CONCLUSIONS: European
      countries differ regarding the frequency and duration of hospitalizations of
      cancer patients in the last month of life. This reflects country-specific
      differences in the organization of palliative care and highlights the important
      role of the GP in palliative care provision.

PMID- 25859158
TI  - The study protocol of: 'Initiating end of life care in stroke: clinical decision
      making around prognosis'.
AB  - BACKGROUND: The initiation of end of life care in an acute stroke context should
      be focused on those patients and families with greatest need. This requires
      clinicians to synthesise information on prognosis, patterns (trajectories) of
      dying and patient and family preferences. Within acute stroke, prognostic models
      are available to identify risks of dying, but variability in dying trajectories
      makes it difficult for clinicians to know when to commence palliative
      interventions. This study aims to investigate clinicians' use of different types
      of evidence in decisions to initiate end of life care within trajectories typical
      of the acute stroke population. METHODS/DESIGN: This two-phase, mixed methods
      study comprises investigation of dying trajectories in acute stroke (Phase 1),
      and the use of clinical scenarios to investigate clinical decision-making in the
      initiation of palliative care (Phase 2). It will be conducted in four acute
      stroke services in North Wales and North West England. Patient and public
      involvement is integral to this research, with service users involved at each
      stage. DISCUSSION: This study will be the first to examine whether patterns of
      dying reported in other diagnostic groups are transferable to acute stroke care.
      The strengths and limitations of the study will be considered. This research will
      produce comprehensive understanding of the nature of clinical decision-making
      around end of life care in an acute stroke context, which in turn will inform the
      development of interventions to further build staff knowledge, skills and
      confidence in this challenging aspect of acute stroke care.

PMID- 25859159
TI  - A modified systematic review of research evidence about education for pre
      registration nurses in palliative care.
AB  - BACKGROUND: We undertook a modified systematic review of research regarding
      educational approaches to and effectiveness of pre-registration palliative care
      nursing, to inform the development of a short course in palliative care for pre
      registration nursing students in Cameroon. The aim of this review was to examine
      educational approaches applied to pre-registration palliative care nursing
      education and their effectiveness, and to discuss implications for the
      development of palliative care curricula in resource-poor countries. METHOD: A
      modified systematic review of research on palliative care educational
      interventions, conducted with pre-registration student nurses was undertaken.
      Relevant literature was gathered from CINAHL, EMBASE, MEDLINE and PsychINFO
      databases for the period 2000-2013. Inclusion was limited to studies of
      educational interventions evaluating the effectiveness and outcomes of palliative
      and end of life care education with pre-registration student nurses. RESULTS: 17
      studies were found, all of which were conducted in resource-rich countries:
      United States of America, Canada, Australia, and United Kingdom. Palliative care
      nursing education at pre-registration level is either delivered as a discrete
      course within the curriculum or palliative care content is embedded into other
      nursing specialty courses throughout the wider curriculum. Palliative care
      education is delivered to students at a variety of stages in their nursing
      program, using a mix of both didactic and experiential educational strategies.
      Course facilitators span palliative care specialists, educators who have attended
      'train-the-trainer' courses in palliative care, and nurses with hospice
      experience. Education is underpinned by transformative and experiential learning
      theories and reported as effective in improving students' attitudes towards care
      of the dying. CONCLUSION: The educational strategies identified in this review
      may be applicable to resource-poor countries. However, there are challenges in
      transferability because of the lack of availability of specialist palliative care
      practitioners who can serve as educators, specialist palliative care
      units/institutions for experiential learning, funds to design and use high
      fidelity simulations, and palliative care textbooks and other educational
      materials. There is thus a need for innovative educational strategies that can
      bridge these barriers in resource-poor countries. There is also a need for
      further research into how palliative care education impacts on pre-registration
      student nurses' knowledge and practice.

PMID- 25859161
TI  - Initiating decision-making conversations in palliative care: an ethnographic
      discourse analysis.
AB  - BACKGROUND: Conversations about end-of-life care remain challenging for health
      care providers. The tendency to delay conversations about care options represents
      a barrier that impedes the ability of terminally-ill patients to participate in
      decision-making. Family physicians with a palliative care practice are often
      responsible for discussing end-of-life care preferences with patients, yet there
      is a paucity of research directly observing these interactions. In this study, we
      sought to explore how patients and family physicians initiated decision-making
      conversations in the context of a community hospital-based palliative care
      service. METHODS: This qualitative study combined discourse analysis with
      ethnographic methods. The field research lasted one year, and data were generated
      through participant observation and audio-recordings of consultations. A total of
      101 consultations were observed longitudinally between 18 patients, 6 family
      physicians and 2 pivot nurses. Data analysis consisted in exploring the different
      types of discourses initiating decision-making conversations and how these
      discourses were affected by the organizational context in which they took place.
      RESULTS: The organization of care had an impact on decision-making conversations.
      The timing and origin of referrals to palliative care shaped whether patients
      were still able to participate in decision-making, and the decisions that
      remained to be made. The type of decisions to be made also shaped how
      conversations were initiated. Family physicians introduced decision-making
      conversations about issues needing immediate attention, such as symptom
      management, by directly addressing or eliciting patients' complaints. When
      decisions involved discussing impending death, decision-making conversations were
      initiated either indirectly, by prompting the patients to express their
      understanding of the disease and its progression, or directly, by providing a
      justification for broaching a difficult topic. CONCLUSIONS: Decision-making
      conversations and the initiation thereof were framed by the organization of care
      and the referral process prior to initial encounters. While symptom management
      was taken for granted as part of health care professionals' expected role,
      engaging in decisions regarding preparation for death implicitly remained under
      patients' control. This work makes important clinical contributions by exposing
      the rhetorical function of family physicians' discourse when introducing
      palliative care decisions.

PMID- 25859160
TI  - Factors associated with the designation of a health care proxy and writing
      advance directives for patients suffering from haematological malignancies.
AB  - BACKGROUND: During the last few decades, patients' rights have been reinforced in
      many countries by acts of law. Measures now include health care proxies to uphold
      the doctor-patient relationship and advance directives for end-of-life patients.
      These could be relevant tools as early as the initial diagnosis of haematological
      malignancies because of the uncertain disease course. The aim of this research
      was to assess the factors associated with the designation of a proxy and writing
      advance directives by patients in a haematology department in France. METHODS:
      After a specific programme to encourage discussions about end-of-life
      preferences, we conducted a mixed-methods study comprising retrospective analysis
      of a random sample of 200 patients' medical records, crossed with a qualitative
      analysis of the content of advance directives. Statistical analysis was performed
      by the RKward V 0.6.1 software with 0.05 denoting significance. The study was
      performed and presented in accordance with the STROBE guidelines. A thematic
      analysis of the advance directives was performed by two researchers. RESULTS: A
      total of 197 medical records were evaluable. The mean age of the patients was 66
      years (range: 18-91). Nearly 2/3 of them (64.5%) designated a proxy, 6.1% wrote
      advance directives, and 8.1% and 4.6% expressed a wish to meet a religious
      representative or a volunteer, respectively. The 2-year survival rate was 78.4%
      [95%CI: 68.2-90.2]. Patients who wrote advance directives were statistically
      older (p <0.00025). Patients who wrote an advance directive were more likely to
      have expressed a wish to meet a religious representative (p <0.001) or a
      volunteer (p = 0.003). Marital status was a significant factor in appointing a
      proxy (p = 0.04). CONCLUSIONS: To the best of our knowledge, this is the first
      paper to identify influencing factors for proxies and advance directives in a
      homogenous population of patients with haematological malignancies. Most patients
      chose a proxy. However, despite several training programmes for the carers and a
      care planning programme, few patients wrote advance directives. Our findings
      suggest that influencing factors are advanced age and a wish to see a religious
      representative. This study highlights the importance of oral communication about
      end-of-life issues between carers, patients and their relatives.

PMID- 25859162
TI  - A reliable method for the detection of BRCA1 and BRCA2 mutations in fixed tumour
      tissue utilising multiplex PCR-based targeted next generation sequencing.
AB  - BACKGROUND: Germline mutations in BRCA1 or BRCA2 lead to a high lifetime
      probability of developing ovarian or breast cancer. These genes can also be
      involved in the development of non-hereditary tumours as somatic BRCA1/2
      pathogenic variants are found in some of these cancers. Since patients with
      somatic BRCA pathogenic variants may benefit from treatment with poly ADP ribose
      polymerase inhibitors, it is important to be able to test for somatic changes in
      routinely available tumour samples. Such samples are typically formalin-fixed
      paraffin-embedded (FFPE) tissue, where the extracted DNA tends to be highly
      fragmented and of limited quantity, making analysis of large genes such as BRCA1
      and BRCA2 challenging. This is made more difficult as somatic changes may be
      evident in only part of the sample, due to the presence of normal tissue.
      METHODS: We examined the feasibility of analysing DNA extracted from FFPE ovarian
      and breast tumour tissue to identify significant DNA variants in BRCA1/ BRCA2
      using next generation sequencing methods that were sensitive enough to detect low
      level mutations, multiplexed to reduce the amount of DNA required and had short
      amplicon design. The utility of two GeneRead DNAseq Targeted Exon Enrichment
      Panels with different designs targeting only BRCA1/2 exons, and the Ion AmpliSeq
      BRCA community panel, followed by library preparation and adaptor ligation using
      the TruSeq DNA PCR-Free HT Sample Preparation Kit and NGS analysis on the MiSeq
      were investigated. RESULTS: Using the GeneRead method, we successfully analysed
      over 76% of samples, with >95% coverage of BRCA1/2 coding regions and a mean
      average read depth of >1000-fold. All mutations identified were confirmed where
      possible by Sanger sequencing or replication to eliminate the risk of false
      positive results due to artefacts within FFPE material. Admixture experiments
      demonstrated that BRCA1/2 variants could be detected if present in >10% of the
      sample. A sample subset was evaluated using the Ion AmpliSeq BRCA panel,
      achieving >99% coverage and sufficient read depth for a proportion of the
      samples. CONCLUSIONS: Detection of BRCA1/2 variants in fixed tissue is feasible,
      and could be performed prospectively to facilitate optimum treatment decisions
      for ovarian or breast cancer patients.

PMID- 25859163
TI  - Apigenin, a dietary flavonoid, inhibits proliferation of human bladder cancer T
      24 cells via blocking cell cycle progression and inducing apoptosis.
AB  - BACKGROUND: Apigenin is a nontoxic dietary flavonoid, and it may have
      chemopreventive and therapeutic potential as an anti-inflammatory, antioxidant,
      and anti-cancer agent. However, its role in bladder cancer remains poorly
      understood. The aim of this study was to investigate the anti-proliferative
      activity of apigenin in human bladder cancer T-24 cells. METHODS AND RESULTS:
      Apigenin inhibited T-24 cell proliferation in a dose-dependent manner. We
      demonstrated that apigenin-induced early and mid-apoptotic cell could be
      identified by Annexnin V-Alexa Fluor 488/PI apoptosis detection and TUNEL assay.
      Moreover, using a JC-1 staining assay, we found that apigenin may induce the loss
      of the mitochondrial membrane potential. By performing flow cytometry and Western
      blotting, apigenin-mediated subG1 phase acculmulation was also associated with an
      increase in the phospho-p53, p53, p21, and p27 levels, and with a decrease in the
      Cyclin A, Cyclin B1, Cyclin E, CDK2, Cdc2, and Cdc25C levels, thereby blocking
      cell cycle progression. ELISA showed that the subG1 phase acculmulation was due
      to the increase in the p53, p21, and p27 levels. In addition, apigenin increased
      the Bax, Bad, and Bak levels, but reduced the Bcl-xL, Bcl-2, and Mcl-1 levels,
      and subsequently triggered the mitochondrial apoptotic pathway (release of
      cytochrome c and activation of caspase-9, caspase-3, caspase-7, and PARP).
      Further analysis demonstrated that apigenin increased the ROS levels and depleted
      GSH in T-24 cells at 12 h. CONCLUSIONS: The results suggested that apigenin
      inhibits T-24 cells proliferation via blocking cell cycle progression and
      inducing apoptosis. In addition, we discovered a potential anticancer activity of
      apigenin against T-24 cells.

PMID- 25859164
TI  - Bursts of Self-Conscious Emotions in the Daily Lives of Emerging Adults.
AB  - Self-conscious emotions play a role in regulating daily achievement strivings,
      social behavior, and health, but little is known about the processes underlying
      their daily manifestation. Emerging adults (n = 182) completed daily diaries for
      eight days and multilevel models were estimated to evaluate whether, how much,
      and why their emotions varied from day-to-day. Within-person variation in
      authentic pride was normally-distributed across people and days whereas the other
      emotions were burst-like and characterized by zero-inflated, negative binomial
      distributions. Perceiving social interactions as generally communal increased the
      odds of hubristic pride activation and reduced the odds of guilt activation;
      daily communal behavior reduced guilt intensity. Results illuminated processes
      through which meaning about the self-in-relation-to-others is constructed during
      a critical period of development.

PMID- 25859165
TI  - A review of the treatment of type 2 diabetes in children.
AB  - The incidence of type 2 diabetes and obesity in children and adolescents has
      risen at staggering rates. Studies have shown that treating type 2 diabetes with
      oral medications in children may be more difficult than treating in adults.
      Compounding this problem is the fact that most of the medications available for
      treating type 2 diabetes have not been studied in children. Recently, the
      American Diabetes Association and the Pediatric Endocrine Society have
      collaborated to create a guideline for the treatment of type 2 diabetes in
      children. Similar to the treatment of adults with type 2 diabetes, metformin
      remains the mainstay of therapy along with diet and exercise. Adjunctive therapy
      should be based on the limited clinical evidence available as well as on patient
      preference. In order to avoid detrimental microvascular and macrovascular
      complications, patients, clinicians, and family members should work together to
      ensure adequate treatment of type 2 diabetes in children. 

PMID- 25859166
TI  - Voriconazole monitoring in children with invasive fungal infections.
AB  - OBJECTIVES: The primary objective of this study was to determine the optimal
      daily dose of voriconazole required to achieve therapeutic trough concentrations
      in children 1 month to 18 years of age. The secondary objective was to analyze
      the association between voriconazole trough concentrations and clinical and
      microbiological outcomes, toxicity, and mortality. METHODS: This study was a
      retrospective chart review (October 2009 to August 2012) of pediatric
      oncology/bone marrow transplant patients with proven or probable invasive fungal
      infections treated with intravenous or oral voriconazole. Patients were excluded
      if they were older than 18 years of age, had no voriconazole concentrations drawn
      during the study period, or received voriconazole prior to the study period.
      RESULTS: Thirty-four patients were reviewed; 11 patients met all criteria for
      inclusion. There were 6 males and 5 females, with a median age of 8 years (range:
      0.8-14.8) and a median weight of 27 kg (range: 9-74). Doses were adjusted to a
      median 6 mg/kg/dose (range: 3-8.7 mg/kg/dose) given every 8 (n = 5) to 12 (n = 6)
      hours; dose regimens varied greatly. All but 1 child achieved a voriconazole
      trough concentration above 1 mg/L; 7 children had a trough concentration above 2
      mg/L. The median time to achieve a therapeutic trough concentration was 11 days
      (range: 6-37 days). Therapy failed for 4 of 11 patients, including 3 of the 4
      youngest patients (p=0.022). Three of the 4 for whom therapy failed also had
      voriconazole trough concentrations less than 2 mg/L; this did not reach
      statistical significance. Voriconazole therapy was discontinued in 2 patients due
      to toxicity. CONCLUSIONS: This study confirmed that voriconazole pharmacokinetics
      vary greatly in pediatric oncology/bone marrow transplant patients. "Optimal"
      doses varied over nearly a 3-fold range. Younger patients may be at greater risk
      of poor outcomes and may require additional monitoring and dose adjustment.

PMID- 25859167
TI  - Development and validation of weight, height and age bands to guide the
      prescription of fixed-dose dispersible tablet formulations.
AB  - OBJECTIVES: Conversion of pediatric essential drugs from syrup to dispersible
      tablet formulations would require fixed dose options guided by the weight band in
      which a child falls or a proxy for weight, such as height or age. The purpose of
      this study was to determine whether weight, height, or age bands can be created
      that would lead to greater than 95% of children receiving a therapeutic dose of 6
      commonly prescribed essential drugs, including paracetamol, iron sulfate,
      amoxicillin, co-trimoxazole (i.e., trimethoprim/sulfamethoxazole), ciprofloxacin,
      and co-artemether (i.e., artemether/lumefantrine). METHODS: Using World Health
      Organization growth standards, we created 4 weight bands and then matched them to
      height and age 50th percentile growth curves. The resulting weight, height, and
      age bands were then applied to Ugandan and Bangladeshi anthropometric data sets,
      and the percentage of children who would have received a correct therapeutic dose
      based upon weight, height, or age was determined. This percentage was interpreted
      as acceptable if >95%, marginal if 90% to 95% and unacceptable if <90%. RESULTS:
      Applying the 4 weight bands to the 6 selected drugs, greater than 95% of children
      would have received an acceptable therapeutic dose across the 4 weight bands for
      each of the 6 drugs tested. None of the drugs tested would deliver an acceptable
      therapeutic dose across all bands based upon height or age among Ugandan
      children, and only co-trimoxazole would have been delivered at acceptable
      therapeutic levels based upon these bands in Bangladeshi children. CONCLUSIONS:
      For the 6 drugs tested, dispersible tablets prescribed on the basis of a 4-dose
      regimen determined by weight bands would deliver an acceptable therapeutic dose
      greater than 95% of the time. Substituting weight for age or height bands would
      result in unacceptable levels of under- or overdosing.

PMID- 25859168
TI  - Evaluation of Enoxaparin Dosing and Monitoring in Pediatric Patients at
      Children's Teaching Hospital.
AB  - OBJECTIVES: The primary objective of this study was to evaluate whether empirical
      enoxaparin doses according to Chest guidelines resulted in therapeutic antifactor
      Xa concentrations in pediatric patients. Secondary objectives were to determine
      the median enoxaparin dose that resulted in therapeutic anticoagulation, the
      median time to therapeutic concentrations, and the percentage of patients who
      experienced major bleeding. METHODS: Patients in a tertiary medical center who
      were <18 years of age and received treatment doses of enoxaparin between July
      2007 and June 2010 were included. Patients with <2 antifactor Xa concentrations
      or with only supratherapeutic concentrations and doses that were higher than
      recommended by the guidelines were excluded. Subgroup analysis was conducted by
      dividing children into 4 age groups: <2 months of age, 2 months to <1 year of
      age, 1 year to <3 years of age, and 3 to 17 years of age. RESULTS: Thirty-two
      patients were included in the study. Thirty-seven percent of the patients
      achieved a therapeutic drug level with empirical dosing. The therapeutic dose
      ranged from 1 to 1.9 mg/kg in patients <1 year old, and 0.6 to 1.5 mg/kg in those
      =1 year of age. Comparison of the median therapeutic doses for patients 2 months
      to <1 year to that for patients =1 year old using the Mann-Whitney U test showed
      the median doses to be significantly difierent between the 2 groups (p=0.01). The
      antifactor Xa level became therapeutic on day 5 (median). There were no major
      bleeding events. CONCLUSION: Less than 40% of patients were therapeutic with
      empirical dosing, which supports findings from other studies that suggest a need
      for modification of empirical treatment dosing of enoxaparin in children.

PMID- 25859169
TI  - Time to first antimicrobial administration after onset of sepsis in critically
      ill children.
AB  - OBJECTIVES: Delay of antimicrobial administration in adult patients with severe
      sepsis and septic shock has been associated with a decrease in survival to
      hospital discharge. The primary objective of this investigation was to determine
      the time to first antimicrobial administration after the onset of sepsis in
      critically ill children. Secondary objectives included appropriateness of empiric
      antimicrobials and microbiological testing, fluid resuscitation during the first
      24 hours after onset of sepsis, intensive care unit and hospital length of stay,
      and mortality. METHODS: Retrospective, chart review of all subjects less than or
      equal to 18 years of age admitted to the pediatric intensive care unit (PICU)
      with a diagnosis of sepsis between January 1, 2011, and December 31, 2012.
      RESULTS: A total of 72 subjects met the inclusion criteria during the study
      period. Median time to first antimicrobial administration by a nurse after the
      onset of sepsis was 2.7 (0.5-5.1) hours. Cultures were drawn prior to
      administration of antimicrobials in 91.7% of subjects and were repeated within 48
      hours in 72.2% of subjects. Empiric antimicrobial regimens were appropriate in
      91.7% of cases. The most common empiric antimicrobial regimens included
      piperacillin/tazobactam plus vancomycin in 19 subjects (26.4%) and ceftriaxone
      plus vancomycin in 15 subjects (20.8%). Median PICU length of stay was 129 (64.6
      370.9) hours, approximately 5 days, and median hospital length of stay was 289
      (162.5-597.1) hours, approximately 12 days. There were 4 deaths during the study
      period. CONCLUSIONS: Time to first antimicrobial administration after onset of
      sepsis was not optimal and exceeded the recommendations set forth in
      international guidelines. At our institution, the process for treating pediatric
      patients with severe sepsis and septic shock should be modified to increase
      compliance with national guidelines.

PMID- 25859170
TI  - Effects of Clonidine on Withdrawal From Long-term Dexmedetomidine in the
      Pediatric Patient.
AB  - OBJECTIVE: To compare withdrawal symptoms among pediatric intensive care patients
      receiving clonidine to those not receiving clonidine while being weaned from long
      term dexmedetomidine. METHODS: This retrospective analysis evaluated Withdrawal
      Assessment Tool-1 (WAT-1) scores and hemodynamic parameters in pediatric patients
      on dexmedetomidine for 5 days or longer between January 1, 2009, and December 31,
      2012. The primary objective was to compare withdrawal symptoms based on the
      number of elevated WAT-1 scores among patients on clonidine to those not on
      clonidine, while being weaned from long-term dexmedetomidine. The secondary
      objective was to describe withdrawal symptoms associated with long-term
      dexmedetomidine use. RESULTS: Nineteen patients (median age, 1.5 years;
      interquartile range [IQR], 0.67-3.3) received 20 treatment courses of
      dexmedetomidine for at least 5 days. Clonidine was received by patients during 12
      of the treatment courses. The patients in the clonidine group had an average of
      0.8 (range, 0-6) elevated WAT-1 scores 24 hours post wean compared to an average
      of 3.2 (0-8) elevated WAT-1 scores in the no clonidine group (p = 0.49). There
      were no significant difierences between prewean and postwean systolic or
      diastolic blood pressures among the 2 groups. The average heart rate during the
      postwean period was 112 beats per minute (bpm) (range, 88.5-151.5) in the
      clonidine group compared to 138.4 bpm (range, 117.8-168.3) in the no clonidine
      group (p = 0.003). In the clonidine group, the mean change in heart rate postwean
      compared to prewean was an increase of 3.6 bpm (range, -39.6 to 47.5), compared
      to a mean increase of 29.9 bpm (range, 5.5-74.7) in the no clonidine group (p =
      0.042). CONCLUSIONS: There was no difierence in WAT-1 scores between groups, with
      the clonidine group displaying a trend towards fewer elevated WAT-1 scores during
      the 24 hours post dexmedetomidine wean. Patients who received clonidine had
      significantly lower heart rates than the no clonidine group.

PMID- 25859171
TI  - A prospective, open-label trial of clevidipine for controlled hypotension during
      posterior spinal fusion.
AB  - OBJECTIVES: Controlled hypotension is one means to limit or avoid the need for
      allogeneic blood products. Clevidipine is a short-acting, intravenous calcium
      channel antagonist with a half-life of 1 to 3 minutes due to rapid metabolism by
      non-specific blood and tissue esterases. To date, there are no prospective
      evaluations with clevidipine in the pediatric population. We prospectively
      evaluated the dosing requirements, efficacy, and safety of clevidipine for
      ontrolled hypotension during spinal surgery for neuromuscular scoliosis in the
      pediatric population. METHODS: Patients undergoing posterior spinal fusion for
      neuromuscular scoliosis were eligible for inclusion. The study was an open label,
      observational study. Maintenance anesthesia included desflurane titrated to
      maintain a bispectral index at 40 to 60 and a remifentanil infusion. Motor and
      somatosensory evoked potentials were monitored intraoperatively. When the mean
      arterial pressure (MAP) was >= 65 mmHg despite remifentanil at 0.3 mcg/kg/min,
      clevidipine was added to maintain the MAP at 55 to 65 mmHg. Clevidipine was
      initiated at 0.25 to 1 mcg/kg/min and titrated up in increments of 0.25 to 1
      mcg/kg/min every 3 to 5 minutes to achieve the desired MAP. RESULTS: The study
      cohort included 45 patients. Fifteen patients (33.3%) did not require a
      clevidipine infusion to maintain the desired MAP range, leaving 30 patients
      including 13 males and 17 females for analysis. These patients ranged in age from
      7.9 to 17.4 years (mean +/- SD: 13.7 +/- 2.2 years) and in weight from 18.9 to
      78.1 kg (mean +/- SD: 43.4 +/- 14.2 kg). Intraoperatively, the clevidipine
      infusion was stopped in 6 patients as the surgeon expressed concerns regarding
      spinal cord perfusion and requested a higher MAP than the study protocol allowed.
      The data until that point were included for analysis. The target MAP was
      initially achieved at a mean time of 8.9 minutes. Sixteen of the 30 patients
      (53.3%) achieved the target MAP within 5 minutes. Heart rate (HR) increased from
      a baseline of 83 +/- 16 to 86 +/- 15 beats per minute (mean +/- SD) (p=0.04) with
      the administration of clevidipine. No patient had a HR increase >= 20 beats per
      minute or required the administration of a beta-adrenergic antagonist. The
      duration of the clevidipine administration varied from 8 to 527 minutes (mean +/-
      SD: 160 +/- 123 minutes). The maintenance infusion rate of clevidipine varied
      from 0.25 to 5.0 mcg/kg/min (mean +/- SD: 1.4 +/- 1.1 mcg/kg/min). Clevidipine
      was paused a total of 43 times in the 30 cases. In 18 of the 30 patients (60%),
      the clevidipine infusion was temporarily paused more than once due to a MAP < 55
      mmHg. A fluid bolus was administered to only 1 patient to treat the low MAP. No
      patient required the administration of a vasoactive agent for hypotension. When
      the clevidipine infusion was discontinued as controlled hypotension was no longer
      required, the MAP returned to baseline or >= 65 mmHg within 10 minutes in 12 of
      the 30 patients (40%). CONCLUSIONS: Clevidipine can be used to provide controlled
      hypotension during posterior spinal fusion. The response of the MAP, both the
      onset and duration of action, were rapid. Although titration of the infusion with
      occasional pauses of administration may be needed, excessive hypotension was not
      noted.

PMID- 25859172
TI  - Successful Use of Daptomycin in a Preterm Neonate With Persistent Methicillin
      Resistant Staphylococcus epidermidis Bacteremia.
AB  - There is limited information regarding the use of daptomycin in the neonatal
      population, and dosage adjustments for neonates with renal dysfunction. We report
      on the successful use of daptomycin in a 1-month-old, former 24-week gestation
      neonate with persistent methicillin-resistant Staphylococcus epidermidis (MRSE)
      bacteremia and impaired renal function. We also review the available literature
      supporting daptomycin use in the neonatal period. Daptomycin peak and trough
      serum levels were obtained immediately prior to and 60 minutes after the fifth
      dose. While vancomycin remains the drug of choice for methicillin-resistant
      Staphylococcal infections, due to increasing reports of treatment failures,
      alternative therapies are recommended. Based on mounting evidence, daptomycin may
      be considered an option in persistently bacteremic neonates who fail vancomycin
      therapy, although further investigation is warranted. 

PMID- 25859173
TI  - Continuous Inhalation of Ipratropium Bromide for Acute Asthma Refractory to beta2
      agonist Treatment.
AB  - To present the case of a patient with persistent bronchospasm, refractory to
      treatment with beta2-agonists, that resolved promptly with continuous inhalation
      of large dose (1000 mcg/hr) ipratropium bromide, and to discuss the possibility
      of tolerance to beta2-agonists as the cause for his failure to respond to
      adrenergic medications. The patient had received multiple doses of albuterol, as
      well as subcutaneous terbutaline (0.3 mg), intravenous magnesium sulfate (1 g)
      and intravenous dexamethasone (10 mg) prior to his admission to the intensive
      care unit. He remained symptomatic despite systemic intravenous steroids,
      continuous intravenous terbutaline (up to 0.6 mcg/kg/min), and continuous
      nebulized albuterol (up to 20 mg/hr for 57 hr) followed by 49 hours of continuous
      levalbuterol (7 mg/hr). Due to the lack of response, all beta2-agonists were
      discontinued at 106 hours post-admission, and he was started on large dose
      ipratropium bromide (1000 mcg/hr) by continuous nebulization. Clinical
      improvement was evident within 1 hour and complete resolution of his symptoms
      within 4 hours. Continuous inhalation of large dose ipratropium bromide may be an
      effective regimen for the treatment of patients hospitalized with acute asthma
      who are deemed to be nonresponsive and/or tolerant to beta2-agonist therapy. 

PMID- 25859174
TI  - Adverse effects of bronchodilators in infants with bronchiolitis.

PMID- 25859175
TI  - Recent advances in synthesis and biological activity of triterpenic acylated
      oximes.
AB  - During the last few decades more and more attention has been paid to triterpenes
      a group of compounds with five- or four-ring skeleton and carboxyl, hydroxyl or
      oxo groups. Triterpenes with unsubstituted C-3 hydroxyl group can be easily
      transformed into appropriate ketones and then into oximes. The carbonyl group can
      be created not only from the hydroxyl group at C-3 position, but also at C-2, C
      12 or C-28 positions. Several methods of creation of two = NOH groups within one
      molecule of triterpene are known. There are also known triterpenes with two
      carbonyl groups, e.g. at C-3 and C-11 positions, which differ in reactivity:
      among them only C-3 group can be transformed into oxime. A reactive hydroxyimine
      group can undergo the action of acylating agents, such as carboxylic acids or
      their derivatives, also the ones with significant pharmacological activity. Acyl
      derivatives of triterpenic oximes exhibit important pharmacological activity. The
      biological tests performed with the use of cell cultures inoculated with viruses
      showed inhibitory activity of some triterpenic acyloximes against type 1 HSV
      (H7N1), ECHO-6 and HIV-1 viruses. Another acylated oximes derived from
      triterpenes shown cytotoxic or antiproliferative activity against many lines of
      cancer cells. In many cases the pharmacological effects of the tested
      acyloxyiminotriterpenes were comparable to those of appropriate standard drugs.
      One of the newest application of acyl derivatives of triterpenic oximes is their
      ability to form organogels.

PMID- 25859176
TI  - Effectiveness of smoking reduction intervention for hardcore smokers.
AB  - BACKGROUND: The prevalence and correlates of hardcore smokers, who have high
      daily cigarette consumption, no quitting history and no intention to quit, have
      been studied in several western developed countries, but no previous trials of
      smoking cessation have tested intervention effectiveness for these smokers. The
      current study examined if hardcore smokers can benefit from smoking reduction
      intervention to achieve cessation, and explored the underlying reasons. METHODS:
      A posteriori analysis was conducted on data from a randomized controlled trial of
      smoking reduction intervention on 1,154 smokers who did not want to quit. Odds
      ratios of 7-day point prevalence of abstinence, smoking reduction by at least 50%
      and quit attempt at the 6-month follow-up comparing subgroups of smokers were
      analyzed. RESULTS: In hardcore smokers, the odds ratio comparing the quit rate
      between the intervention and control group was 4.18 (95% CI: 0.51-34.65), which
      was greater than non-hardcore smokers (OR = 1.58, 95% CI: 0.98-2.54). The number
      needed to treat for hardcore and non-hardcore smokers was 8.33 (95% CI: 5.56
      16.67) and 16.67 (95% CI: 8.33-233.64), respectively. In smokers who did not have
      quit attempt experience and those who smoked more than 15 cigarettes daily, the
      odds ratio comparing intervention and control group was 3.29 (95% CI: 0.72-14.98)
      and 1.36 (95% CI: 0.78-2.36), respectively. CONCLUSIONS: The a posteriori
      analysis provided pilot results that smoking reduction intervention may be
      effective to help hardcore smokers to quit and reduce smoking. Having no previous
      quit attempt was identified as more important than having large cigarette
      consumption in explaining the greater effectiveness of the intervention.

PMID- 25859178
TI  - An evaluation of prospective motion correction (PMC) for high resolution
      quantitative MRI.
AB  - Quantitative imaging aims to provide in vivo neuroimaging biomarkers with high
      research and diagnostic value that are sensitive to underlying tissue
      microstructure. In order to use these data to examine intra-cortical differences
      or to define boundaries between different myelo-architectural areas, high
      resolution data are required. The quality of such measurements is degraded in the
      presence of motion hindering insight into brain microstructure. Correction
      schemes are therefore vital for high resolution, whole brain coverage approaches
      that have long acquisition times and greater sensitivity to motion. Here we
      evaluate the use of prospective motion correction (PMC) via an optical tracking
      system to counter intra-scan motion in a high resolution (800 MUm isotropic)
      multi-parameter mapping (MPM) protocol. Data were acquired on six volunteers
      using a 2 * 2 factorial design permuting the following conditions: PMC on/off and
      motion/no motion. In the presence of head motion, PMC-based motion correction
      considerably improved the quality of the maps as reflected by fewer visible
      artifacts and improved consistency. The precision of the maps, parameterized
      through the coefficient of variation in cortical sub-regions, showed improvements
      of 11-25% in the presence of deliberate head motion. Importantly, in the absence
      of motion the PMC system did not introduce extraneous artifacts into the
      quantitative maps. The PMC system based on optical tracking offers a robust
      approach to minimizing motion artifacts in quantitative anatomical imaging
      without extending scan times. Such a robust motion correction scheme is crucial
      in order to achieve the ultra-high resolution required of quantitative imaging
      for cutting edge in vivo histology applications. 

PMID- 25859177
TI  - Abnormal cardiovascular sympathetic and parasympathetic responses to physical and
      emotional stimuli in depersonalization disorder.
AB  - BACKGROUND: Depersonalization disorder (DPD) is characterized by a subjective
      sense of unreality, disembodiment, emotional numbing and reduced psychogenic
      (sudomotor) sympathoexcitation. AIMS: Three related experiments utilized
      escalating physical and emotional challenges in 14 DPD participants and 16
      controls aimed to elucidate (i) whether the cardiovascular sympathetic (SNS) and
      parasympathetic (PNS) nervous systems are implicated in DPD pathophysiology and
      (ii) if possible, to determine whether the blunted sympathoexcitation in DPD is
      peripherally or centrally mediated. METHOD: Participants completed the Beck
      Anxiety Inventory (BAI), Dissociative Experience Scale (DES), and Cambridge
      Depersonalization Scale (CDS). Study I recorded heart rate (HR) and blood
      pressure (BP) during 5 min supine baseline, 3 min sustained handgrip (HG), 3 min
      cold pressor (CP) and 5 min 60 degrees  head-up tilt (HUT). In study II, HR, BP,
      and heart rate variability (HRV) were recorded during 5 min simultaneous 60
      degrees  HUT and continuous presentation of unpleasant images (5 s per image).
      Study III examined HR and BP orienting responses (ORs) to simultaneous 60 degrees
      HUT and pseudorandom presentation of unpleasant, neutral and pleasant images (5
      s per image 3 min 25 s). OR data was grouped by image valence post hoc. RESULTS:
      DPD BAI (p = 0.0004), DES (p = 0.0002), and CDS (p <= 0.0001) scores were higher
      than controls. The DPD group produced diminished diastolic BP (DBP) (p = 0.045)
      increases to HG. Other indices were comparable between groups. DPD participants
      produced diminished systolic BP (SBP) (p = 0.003) and DBP (p = 0.002) increases,
      but greater (p = 0.004) HR increases to CP. In study II, DPD high frequency HRV
      (HF-HRV)-indicating parasympathetic vagal activity-was reduced (p = 0.029). In
      study III, DPD DBP was higher throughout the 5 s duration of HUT/pseudorandom
      unpleasant image presentation (1 s, p = 0.002, 2 s p = 0.033, 3 s p = 0.001, 4 s
      p = 0.009, 5 s p = 0.029). CONCLUSIONS: Study I's BP pressor data supports
      previous findings of suppressed sympathoexcitation in DPD. The greater HR
      increases to CP, decreased HF-HRV in study II, and increased DBP during
      unpleasant ORs in study III implicates the SNS and PNS in DPD pathophysiology.
      These studies suggest the cardiovascular autonomic dysregulation in DPD is likely
      to be centrally-mediated.

PMID- 25859179
TI  - Social buffering suppresses fear-associated activation of the lateral amygdala in
      male rats: behavioral and neurophysiological evidence.
AB  - In social mammals, the presence of an affiliative conspecific reduces stress
      responses, a phenomenon referred to as "social buffering."In a previous study, we
      found that the presence of a conspecific animal ameliorated a variety of stress
      responses to an aversive conditioned stimulus (CS), including freezing and Fos
      expression in the lateral amygdala (LA) of male rats. Although these findings
      suggest that the presence of a conspecific animal suppresses neural activity in
      the LA, direct neurophysiological evidence of suppressed activity in the LA
      during social buffering is still lacking. In the present study, we analyzed
      freezing behavior and local field potentials in the LA of fear-conditioned rats
      in response to the CS, in the presence or absence of a conspecific. After
      auditory aversive conditioning, the CS was presented to the conditioned rats in
      the presence or absence of a conspecific animal, on 2 successive days. The
      presence of a conspecific animal significantly decreased the mean peak amplitudes
      of auditory evoked field potentials, gamma oscillations (25-75 Hz) and high
      frequency oscillations (100-300 Hz) in the LA. Furthermore, magnitudes of these
      neural responses positively correlated with freezing duration of the fear
      conditioned rats. The results provide the first electrophysiological evidence
      that social buffering suppresses CS-induced activation in the LA, which
      consequently reduces conditioned fear responses. 

PMID- 25859180
TI  - Secretory function in subplate neurons during cortical development.
AB  - Subplate cells are among the first generated neurons in the mammalian cerebral
      cortex and have been implicated in the establishment of cortical wiring. In
      rodents some subplate neurons persist into adulthood. Here we would like to
      highlight several converging findings which suggest a novel secretory function of
      subplate neurons during cortical development. Throughout the postnatal period in
      rodents, subplate neurons have highly developed rough endoplasmic reticulum (ER)
      and are under an ER stress condition. By comparing gene expression between
      subplate and layer 6, we found that several genes encoding secreted proteins are
      highly expressed in subplate neurons. One of these secreted proteins,
      neuroserpin, encoded by the serpini1 gene, is localized to the ER in subplate
      cells. We propose that subplate might influence cortical circuit formation
      through a transient secretory function. 

PMID- 25859181
TI  - GluN2D-containing NMDA receptors-mediate synaptic currents in hippocampal
      interneurons and pyramidal cells in juvenile mice.
AB  - The differential regulation of the two major N-methyl-D-aspartate receptor
      (NMDAR) subunits GluN2A and GluN2B during development in forebrain pyramidal
      cells has been thoroughly investigated. In contrast, much less is known about the
      role of GluN2D, which is expressed at low levels and is downregulated following
      the second postnatal week. However, it appears that few cells, presumably
      interneurons, continue to express GluN2D also in juvenile mice. To investigate
      which hippocampal cell types express this subunit, we generated transgenic mice
      with EGFP-tagged GluN2D receptors. The expression of the transgene was confined
      to hippocampal interneurons, most of which were parvalbumin- and/or somatostatin
      positive. Electrophysiological and morphological analyses showed that GluN2D was
      present mainly in fast spiking basket and axo-axonic cells. Based on
      pharmacological evidence and electrophysiological analysis of GluN2D knockout
      mice, we conclude that GluN2D-containing NMDARs mediate synaptic currents in
      hippocampal interneurons of young and juvenile mice and in CA1 pyramidal neurons
      of newborn mice. 

PMID- 25859182
TI  - Functional and structural deficits at accumbens synapses in a mouse model of
      Fragile X.
AB  - Fragile X is the most common cause of inherited intellectual disability and a
      leading cause of autism. The disease is caused by mutation of a single X-linked
      gene called fmr1 that codes for the Fragile X mental retardation protein (FMRP),
      a 71 kDa protein, which acts mainly as a translation inhibitor. Fragile X
      patients suffer from cognitive and emotional deficits that coincide with
      abnormalities in dendritic spines. Changes in spine morphology are often
      associated with altered excitatory transmission and long-term plasticity, the
      most prominent deficit in fmr1-/y mice. The nucleus accumbens, a central part of
      the mesocortico-limbic reward pathway, is now considered as a core structure in
      the control of social behaviors. Although the socio-affective impairments
      observed in Fragile X suggest dysfunctions in the accumbens, the impact of the
      lack of FMRP on accumbal synapses has scarcely been studied. Here we report for
      the first time a new spike timing-dependent plasticity paradigm that reliably
      triggers NMDAR-dependent long-term potentiation (LTP) of excitatory afferent
      inputs of medium spiny neurons (MSN) in the nucleus accumbens core region.
      Notably, we discovered that this LTP was completely absent in fmr1-/y mice. In
      the fmr1-/y accumbens intrinsic membrane properties of MSNs and basal excitatory
      neurotransmission remained intact in the fmr1-/y accumbens but the deficit in LTP
      was accompanied by an increase in evoked AMPA/NMDA ratio and a concomitant
      reduction of spontaneous NMDAR-mediated currents. In agreement with these
      physiological findings, we found significantly more filopodial spines in fmr1-/y
      mice by using an ultrastructural electron microscopic analysis of accumbens core
      medium spiny neuron spines. Surprisingly, spine elongation was specifically due
      to the longer longitudinal axis and larger area of spine necks, whereas spine
      head morphology and postsynaptic density size on spine heads remained unaffected
      in the fmr1-/y accumbens. These findings together reveal new structural and
      functional synaptic deficits in Fragile X. 

PMID- 25859183
TI  - Aging, Alzheimer's, and APOE genotype influence the expression and neuronal
      distribution patterns of microtubule motor protein dynactin-P50.
AB  - Reports from neural cell cultures and experimental animal studies provide
      evidence of age- and disease-related changes in retrograde transport of spent or
      misfolded proteins destined for degradation or recycling. However, few studies
      address these issues in human brain from those who either age without dementia
      and overt neuropathology, or succumb to Alzheimer's; especially as such
      propensity may be influenced by APOE genotype. We studied the expression and
      distribution of the dynein subunit dynactin-P50, the beta amyloid precursor
      protein (betaAPP), and hyperphosphorylated tau (P-tau) in tissues and tissue
      sections of brains from non-demented, neuropathology-free patients and from
      Alzheimer patients, with either APOE epsilon3,3 or APOE epsilon4,4. We found that
      advanced age in patients without dementia or neuropathological change was
      associated with coordinated increases in dynactin-P50 and betaAPP in neurons in
      pyramidal layers of the hippocampus. In contrast, in Alzheimer's, betaAPP and
      dynactin were significantly reduced. Furthermore, the dynactin-P50 and betaAPP
      that was present was located primarily in dystrophic neurites in Abeta plaques.
      Tissues from Alzheimer patients with APOE epsilon3,3 had less P-tau, more
      betaAPP, dynactin-P50, and synaptophysin than did tissues from Alzheimer patients
      carrying APOE epsilon4,4. It is logical to conclude, then, that as neurons age
      successfully, there is coordination between retrograde delivery and maintenance
      and repair, as well as between retrograde delivery and degradation and/or
      recycling of spent proteins. The buildup of proteins slated for repair, synaptic
      viability, transport, and re-cycling in neuron soma and dystrophic neurites
      suggest a loss of this coordination in Alzheimer neurons. Inheritance of APOE
      epsilon3,3 rather than APOE epsilon4,4, is associated with neuronal resilience,
      suggestive of better repair capabilities, more synapses, more efficient
      transport, and less hyperphosphorylation of tau. We conclude that even in disease
      the epsilon3 allele is neuroprotective. 

PMID- 25859184
TI  - A single-cross, RNA interference-based genetic tool for examining the long-term
      maintenance of homeostatic plasticity.
AB  - Homeostatic synaptic plasticity (HSP) helps neurons and synapses maintain
      physiologically appropriate levels of output. The fruit fly Drosophila
      melanogaster larval neuromuscular junction (NMJ) is a valuable model for studying
      HSP. Here we introduce a genetic tool that allows fruit fly researchers to
      examine the lifelong maintenance of HSP with a single cross. The tool is a fruit
      fly stock that combines the GAL4/UAS expression system with RNA interference
      (RNAi)-based knock down of a glutamate receptor subunit gene. With this stock, we
      uncover important new information about the maintenance of HSP. We address an
      open question about the role that presynaptic CaV2-type Ca(2+) channels play in
      NMJ homeostasis. Published experiments have demonstrated that hypomorphic
      missense mutations in the CaV2 alpha1a subunit gene cacophony (cac) can impair
      homeostatic plasticity at the NMJ. Here we report that reducing cac expression
      levels by RNAi is not sufficient to impair homeostatic plasticity. The presence
      of wild-type channels appears to support HSP-even when total CaV2 function is
      severely reduced. We also conduct an RNAi- and electrophysiology-based screen to
      identify new factors required for sustained homeostatic signaling throughout
      development. We uncover novel roles in HSP for Drosophila homologs of Cysteine
      string protein (CSP) and Phospholipase Cbeta (Plc21C). We characterize those
      roles through follow-up genetic tests. We discuss how CSP, Plc21C, and associated
      factors could modulate presynaptic CaV2 function, presynaptic Ca(2+) handling, or
      other signaling processes crucial for sustained homeostatic regulation of NMJ
      function throughout development. Our findings expand the scope of signaling
      pathways and processes that contribute to the durable strength of the NMJ. 

PMID- 25859186
TI  - Corrigendum: Brain scaling in mammalian evolution as a consequence of concerted
      and mosaic changes in numbers of neurons and average neuronal cell size.
AB  - [This corrects the article on p. 77 in vol. 8, PMID: 25157220.]. 

PMID- 25859187
TI  - Corrigendum: Cellular scaling rules for the brain of Artiodactyla include a
      highly folded cortex with few neurons.
AB  - [This corrects the article on p. 128 in vol. 8, PMID: 25429261.]. 

PMID- 25859185
TI  - Differential requirements for Gli2 and Gli3 in the regional specification of the
      mouse hypothalamus.
AB  - Secreted protein Sonic hedgehog (Shh) ventralizes the neural tube by modulating
      the crucial balance between activating and repressing functions (GliA, GliR) of
      transcription factors Gli2 and Gli3. This balance-the Shh-Gli code-is species-
      and context-dependent and has been elucidated for the mouse spinal cord. The
      hypothalamus, a forebrain region regulating vital functions like homeostasis and
      hormone secretion, shows dynamic and intricate Shh expression as well as complex
      regional differentiation. Here we asked if particular combinations of Gli2 and
      Gli3 and of GliA and GliR functions contribute to the variety of hypothalamic
      regions, i.e., we wanted to approach the question of a possible hypothalamic
      version of the Shh-Gli code. Based on mouse mutant analysis, we show that: (1)
      hypothalamic regional heterogeneity is based in part on differentially stringent
      requirements for Gli2 or Gli3; (2) another source of diversity are differential
      requirements for Shh of neural vs. non-neural origin; (3) the medial progenitor
      domain known to depend on Gli2 for its development generates several essential
      hypothalamic nuclei plus the pituitary and median eminence; (4) the suppression
      of Gli3R by neural and non-neural Shh is essential for hypothalamic
      specification. Finally, we have mapped our results on a recent model which
      considers the hypothalamus as a transverse region with alar and basal portions.
      Our data confirm the model and are explained by it. 

PMID- 25859189
TI  - A computational model of pattern separation efficiency in the dentate gyrus with
      implications in schizophrenia.
AB  - Information processing in the hippocampus begins by transferring spiking activity
      of the entorhinal cortex (EC) into the dentate gyrus (DG). Activity pattern in
      the EC is separated by the DG such that it plays an important role in hippocampal
      functions including memory. The structural and physiological parameters of these
      neural networks enable the hippocampus to be efficient in encoding a large number
      of inputs that animals receive and process in their life time. The neural
      encoding capacity of the DG depends on its single neurons encoding and pattern
      separation efficiency. In this study, encoding by the DG is modeled such that
      single neurons and pattern separation efficiency are measured using simulations
      of different parameter values. For this purpose, a probabilistic model of single
      neurons efficiency is presented to study the role of structural and physiological
      parameters. Known neurons number of the EC and the DG is used to construct a
      neural network by electrophysiological features of granule cells of the DG.
      Separated inputs as activated neurons in the EC with different firing
      probabilities are presented into the DG. For different connectivity rates between
      the EC and DG, pattern separation efficiency of the DG is measured. The results
      show that in the absence of feedback inhibition on the DG neurons, the DG
      demonstrates low separation efficiency and high firing frequency. Feedback
      inhibition can increase separation efficiency while resulting in very low single
      neuron's encoding efficiency in the DG and very low firing frequency of neurons
      in the DG (sparse spiking). This work presents a mechanistic explanation for
      experimental observations in the hippocampus, in combination with theoretical
      measures. Moreover, the model predicts a critical role for impaired inhibitory
      neurons in schizophrenia where deficiency in pattern separation of the DG has
      been observed. 

PMID- 25859188
TI  - Hippocampal subfield and medial temporal cortical persistent activity during
      working memory reflects ongoing encoding.
AB  - Previous neuroimaging studies support a role for the medial temporal lobes in
      maintaining novel stimuli over brief working memory (WM) delays, and suggest
      delay period activity predicts subsequent memory. Additionally, slice recording
      studies have demonstrated neuronal persistent spiking in entorhinal cortex,
      perirhinal cortex (PrC), and hippocampus (CA1, CA3, subiculum). These data have
      led to computational models that suggest persistent spiking in parahippocampal
      regions could sustain neuronal representations of sensory information over many
      seconds. This mechanism may support both WM maintenance and encoding of
      information into long term episodic memory. The goal of the current study was to
      use high-resolution fMRI to elucidate the contributions of the MTL cortices and
      hippocampal subfields to WM maintenance as it relates to later episodic
      recognition memory. We scanned participants while they performed a delayed match
      to sample task with novel scene stimuli, and assessed their memory for these
      scenes post-scan. We hypothesized stimulus-driven activation that persists into
      the delay period-a putative correlate of persistent spiking-would predict later
      recognition memory. Our results suggest sample and delay period activation in the
      parahippocampal cortex (PHC), PrC, and subiculum (extending into DG/CA3 and CA1)
      was linearly related to increases in subsequent memory strength. These data
      extend previous neuroimaging studies that have constrained their analysis to
      either the sample or delay period by modeling these together as one continuous
      ongoing encoding process, and support computational frameworks that predict
      persistent activity underlies both WM and episodic encoding. 

PMID- 25859190
TI  - Characterization of mind wandering using fNIRS.
AB  - Assessing whether someone is attending to a task has become important for
      educational and professional applications. Such attentional drifts are usually
      termed mind wandering (MW). The purpose of the current study is to test to what
      extent a recent neural imaging modality can be used to detect MW episodes.
      Functional near infrared spectroscopy is a non-invasive neuroimaging technique
      that has never been used so far to measure MW. We used the Sustained Attention to
      Response Task (SART) to assess when subjects attention leaves a primary task.
      Sixteen-channel fNIRS data were collected over frontal cortices. We observed
      significant activations over the medial prefrontal cortex (mPFC) during MW, a
      brain region associated with the default mode network (DMN). fNIRS data were used
      to classify MW data above chance level. In line with previous brain-imaging
      studies, our results confirm the ability of fNIRS to detect Default Network
      activations in the context of MW. 

PMID- 25859191
TI  - Clinical application of the Hybrid Assistive Limb (HAL) for gait training-a
      systematic review.
AB  - OBJECTIVE: The aim of this study was to review the literature on clinical
      applications of the Hybrid Assistive Limb system for gait training. METHODS: A
      systematic literature search was conducted using Web of Science, PubMed, CINAHL
      and clinicaltrials.gov and additional search was made using reference lists in
      identified reports. Abstracts were screened, relevant articles were reviewed and
      subject to quality assessment. RESULTS: Out of 37 studies, 7 studies fulfilled
      inclusion criteria. Six studies were single group studies and 1 was an
      explorative randomized controlled trial. In total, these studies involved 140
      participants of whom 118 completed the interventions and 107 used HAL for gait
      training. Five studies concerned gait training after stroke, 1 after spinal cord
      injury (SCI) and 1 study after stroke, SCI or other diseases affecting walking
      ability. Minor and transient side effects occurred but no serious adverse events
      were reported in the studies. Beneficial effects on gait function variables and
      independence in walking were observed. CONCLUSIONS: The accumulated findings
      demonstrate that the HAL system is feasible when used for gait training of
      patients with lower extremity paresis in a professional setting. Beneficial
      effects on gait function and independence in walking were observed but data do
      not allow conclusions. Further controlled studies are recommended.

PMID- 25859192
TI  - Predictive coding and multisensory integration: an attentional account of the
      multisensory mind.
AB  - Multisensory integration involves a host of different cognitive processes,
      occurring at different stages of sensory processing. Here I argue that, despite
      recent insights suggesting that multisensory interactions can occur at very early
      latencies, the actual integration of individual sensory traces into an internally
      consistent mental representation is dependent on both top-down and bottom-up
      processes. Moreover, I argue that this integration is not limited to just sensory
      inputs, but that internal cognitive processes also shape the resulting mental
      representation. Studies showing that memory recall is affected by the initial
      multisensory context in which the stimuli were presented will be discussed, as
      well as several studies showing that mental imagery can affect multisensory
      illusions. This empirical evidence will be discussed from a predictive coding
      perspective, in which a central top-down attentional process is proposed to play
      a central role in coordinating the integration of all these inputs into a
      coherent mental representation. 

PMID- 25859193
TI  - Loss of dysbindin-1, a risk gene for schizophrenia, leads to impaired group 1
      metabotropic glutamate receptor function in mice.
AB  - The expression of dysbindin-1, a protein coded by the risk gene dtnbp1, is
      reduced in the brains of schizophrenia patients. Evidence indicates a role of
      dysbindin-1 in dopaminergic and glutamatergic transmission. Glutamatergic
      transmission and plasticity at excitatory synapses is critically regulated by G
      protein coupled metabotropic glutamate receptor (mGluR) family members, that have
      been implicated in schizophrenia. Here, we report a role of dysbindin-1 in
      hippocampal group 1 mGluR (mGluRI) function in mice. In hippocampal
      synaptoneurosomal preparations from sandy (sdy) mice, that have a loss of
      function mutation in dysbindin-1 gene, we observed a striking reduction in mGluRI
      agonist [(S)-3, 5-dihydroxyphenylglycine] (DHPG)-induced phosphorylation of
      extracellular signal regulated kinase 1/2 (ERK1/2). This mGluR-ERK1/2 deficit
      occurred in the absence of significant changes in protein levels of the two
      members of the mGluRI family (i.e., mGluR1 and mGluR5) or in another mGluRI
      signaling pathway, i.e., protein kinase C (PKC). Aberrant mGluRI-ERK1/2 signaling
      affected hippocampal synaptic plasticity in the sdy mutants as DHPG-induced long
      term depression (LTD) at CA1 excitatory synapses was significantly reduced.
      Behavioral data suggest that the mGluRI hypofunction may underlie some of the
      cognitive abnormalities described in sdy mice as the administration of CDPPB (3
      cyano-N-(1, 3-diphenyl-1H-pyrazol-5-yl benzamide), a positive allosteric
      modulator of mGluR5, rescued short-term object recognition and spatial learning
      and memory deficits in these mice. Taken together, our data suggest a novel role
      of dysbindin-1 in regulating mGluRI functions. 

PMID- 25859194
TI  - Dementias show differential physiological responses to salient sounds.
AB  - Abnormal responsiveness to salient sensory signals is often a prominent feature
      of dementia diseases, particularly the frontotemporal lobar degenerations, but
      has been little studied. Here we assessed processing of one important class of
      salient signals, looming sounds, in canonical dementia syndromes. We manipulated
      tones using intensity cues to create percepts of salient approaching ("looming")
      or less salient withdrawing sounds. Pupil dilatation responses and behavioral
      rating responses to these stimuli were compared in patients fulfilling consensus
      criteria for dementia syndromes (semantic dementia, n = 10; behavioral variant
      frontotemporal dementia, n = 16, progressive nonfluent aphasia, n = 12; amnestic
      Alzheimer's disease, n = 10) and a cohort of 26 healthy age-matched individuals.
      Approaching sounds were rated as more salient than withdrawing sounds by healthy
      older individuals but this behavioral response to salience did not differentiate
      healthy individuals from patients with dementia syndromes. Pupil responses to
      approaching sounds were greater than responses to withdrawing sounds in healthy
      older individuals and in patients with semantic dementia: this differential pupil
      response was reduced in patients with progressive nonfluent aphasia and
      Alzheimer's disease relative both to the healthy control and semantic dementia
      groups, and did not correlate with nonverbal auditory semantic function.
      Autonomic responses to auditory salience are differentially affected by dementias
      and may constitute a novel biomarker of these diseases. 

PMID- 25859195
TI  - Neural circuits containing olfactory neurons are involved in the prepulse
      inhibition of the startle reflex in rats.
AB  - Many neuropsychiatric disorders, such as schizophrenia, have been associated with
      olfactory dysfunction and abnormalities in the prepulse inhibition (PPI) response
      to a startle reflex. However, whether these two abnormalities could be related is
      unclear. The present investigations were designed to determine whether
      theblockage of olfactory sensory input by zinc sulfate infusion in the olfactory
      naris (0.5 ml, 0.17 M, ZnE) can disturb the PPI response. Furthermore, a
      bilateral microinjection of lidocaine/MK801 in the olfactory bulb (OB) was
      administered to examine whether the blockage of olfactory sensory input could
      impair the PPI response. To identify the neural projection between olfaction and
      PPI-related areas, trans-synaptic retrograde tracing with the recombinant
      pseudorabies virus (PRV) was used. Our results demonstrated that blockage of
      olfactory sensory input could disturb olfactory behavior. In the function
      studies, we demonstrated that blockage of olfactory sensory input could impair
      the pre-pulse inhibition of the startle response following decreased c-Fos
      expression in relevant brain regions during the PPI responses. Furthermore,
      similar and more robust findings indicated that blockage of olfactory sensory
      input by microinjection of lidocaine/MK801 in the OB could impair the PPI
      response. In the circuit-level studies, we demonstrated that trans-synaptic
      retrograde tracing with PRV exhibited a large portion of labeled neurons in
      several regions of the olfactory cortices from the pedunculopontine tegmental
      nucleus (PPTg). Thus, these data suggest that the olfactory system participates
      in the PPI regulating fields and plays a role in the pre-pulse inhibition of the
      startle response in rats. 

PMID- 25859196
TI  - Temporal self-regulation theory: a neurobiologically informed model for physical
      activity behavior.
AB  - Dominant explanatory models for physical activity behavior are limited by the
      exclusion of several important components, including temporal dynamics,
      ecological forces, and neurobiological factors. The latter may be a critical
      omission, given the relevance of several aspects of cognitive function for the
      self-regulatory processes that are likely required for consistent implementation
      of physical activity behavior in everyday life. This narrative review introduces
      temporal self-regulation theory (TST; Hall and Fong, 2007, 2013) as a new
      explanatory model for physical activity behavior. Important features of the model
      include consideration of the default status of the physical activity behavior, as
      well as the disproportionate influence of temporally proximal behavioral
      contingencies. Most importantly, the TST model proposes positive feedback loops
      linking executive function (EF) and the performance of physical activity
      behavior. Specifically, those with relatively stronger executive control (and
      optimized brain structures supporting it, such as the dorsolateral prefrontal
      cortex (PFC)) are able to implement physical activity with more consistency than
      others, which in turn serves to strengthen the executive control network itself.
      The TST model has the potential to explain everyday variants of incidental
      physical activity, sport-related excellence via capacity for deliberate practice,
      and variability in the propensity to schedule and implement exercise routines. 

PMID- 25859197
TI  - Eye movement instructions modulate motion illusion and body sway with Op Art.
AB  - Op Art generates illusory visual motion. It has been proposed that eye movements
      participate in such illusion. This study examined the effect of eye movement
      instructions (fixation vs. free exploration) on the sensation of motion as well
      as the body sway of subjects viewing Op Art paintings. Twenty-eight healthy
      adults in orthostatic stance were successively exposed to three visual stimuli
      consisting of one figure representing a cross (baseline condition) and two Op Art
      paintings providing sense of motion in depth-Bridget Riley's Movements in Squares
      and Akiyoshi Kitaoka's Rollers. Before their exposure to the Op Art images,
      participants were instructed either to fixate at the center of the image
      (fixation condition) or to explore the artwork (free viewing condition). Posture
      was measured for 30 s per condition using a body fixed sensor (accelerometer).
      The major finding of this study is that the two Op Art paintings induced a larger
      antero-posterior body sway both in terms of speed and displacement and an
      increased motion illusion in the free viewing condition as compared to the
      fixation condition. For body sway, this effect was significant for the Riley
      painting, while for motion illusion this effect was significant for Kitaoka's
      image. These results are attributed to macro-saccades presumably occurring under
      free viewing instructions, and most likely to the small vergence drifts during
      fixations following the saccades; such movements in interaction with visual
      properties of each image would increase either the illusory motion sensation or
      the antero-posterior body sway. 

PMID- 25859198
TI  - Factors influencing the latency of simple reaction time.
AB  - Simple reaction time (SRT), the minimal time needed to respond to a stimulus, is
      a basic measure of processing speed. SRTs were first measured by Francis Galton
      in the 19th century, who reported visual SRT latencies below 190 ms in young
      subjects. However, recent large-scale studies have reported substantially
      increased SRT latencies that differ markedly in different laboratories, in part
      due to timing delays introduced by the computer hardware and software used for
      SRT measurement. We developed a calibrated and temporally precise SRT test to
      analyze the factors that influence SRT latencies in a paradigm where visual
      stimuli were presented to the left or right hemifield at varying stimulus onset
      asynchronies (SOAs). Experiment 1 examined a community sample of 1469 subjects
      ranging in age from 18 to 65. Mean SRT latencies were short (231, 213 ms when
      corrected for hardware delays) and increased significantly with age (0.55
      ms/year), but were unaffected by sex or education. As in previous studies, SRTs
      were prolonged at shorter SOAs and were slightly faster for stimuli presented in
      the visual field contralateral to the responding hand. Stimulus detection time
      (SDT) was estimated by subtracting movement initiation time, measured in a
      speeded finger tapping test, from SRTs. SDT latencies averaged 131 ms and were
      unaffected by age. Experiment 2 tested 189 subjects ranging in age from 18 to 82
      years in a different laboratory using a larger range of SOAs. Both SRTs and SDTs
      were slightly prolonged (by 7 ms). SRT latencies increased with age while SDT
      latencies remained stable. Precise computer-based measurements of SRT latencies
      show that processing speed is as fast in contemporary populations as in the
      Victorian era, and that age-related increases in SRT latencies are due primarily
      to slowed motor output. 

PMID- 25859199
TI  - Experience, cortisol reactivity, and the coordination of emotional responses to
      skydiving.
AB  - Physiological habituation to laboratory stressors has previously been
      demonstrated, although the literature remains equivocal. Previous studies have
      found skydiving to be a salient naturalistic stressor that elicits a robust
      subjective and physiological stress response. However, it is uncertain whether
      (or how) stress reactivity habituates to this stressor given that skydiving
      remains a risky, life-threatening challenge with every jump despite experience.
      While multiple components of the stress response have been documented, it is
      unclear whether an individual's subjective emotions are related to their
      physiological responses. Documenting coordinated responsivity would lend insight
      into shared underlying mechanisms for the nature of habituation of both
      subjective (emotion) and objective (cortisol) stress responses. Therefore, we
      examined subjective emotion and cortisol responses in first-time compared to
      experienced skydivers in a predominantly male sample (total n = 44; males = 32,
      females = 12). Hierarchical linear modeling (HLM) revealed that experienced
      skydivers showed less reactivity and faster recovery compared to first-time
      skydivers. Subjective emotions were coordinated with physiological responses
      primarily within first-time skydivers. Pre-jump anxiety predicted cortisol
      reactivity within first-time, but not experienced, skydivers. Higher post-jump
      happiness predicted faster cortisol recovery after jumping although this effect
      overlapped somewhat with the effect of experience. Results suggest that
      experience may modulate the coordination of emotional response with cortisol
      reactivity to skydiving. Prior experience does not appear to extinguish the
      stress response but rather alters the individual's engagement of the HPA axis. 

PMID- 25859200
TI  - Personal involvement is related to increased search motivation and associated
      with activity in left BA44-a pilot study.
AB  - Numerous studies explore consumer perception of brands in a more or less passive
      way. This may still be representative for many situations or decisions we make
      each day. Nevertheless, sometimes we often actively search for and use
      information to make informed and reasoned choices, thus implying a rational and
      thinking consumer. Researchers suggested describing this distinction as low
      relative to high involvement consumer behavior. Although the involvement concept
      has been widely used to explain consumer behavior, behavioral and neural
      correlates of this concept are poorly understood. The current study aims to
      describe a behavioral measure that is associated with high involvement, the
      length of search behavior. A second aim of this study was to explore brain
      activations associated with involvement by employing functional magnetic
      resonance imaging (fMRI). We presented participants information cues for
      different products and told them that they had to answer questions with respect
      to these products at the end of the experiment. Participants were free to stop
      the information search if they think they gathered enough information or to
      continue with collecting information. Behavioral results confirmed our hypothesis
      of a relationship between searching behavior and personal involvement by
      demonstrating that the length of search correlated significantly with the degree
      of personal involvement of the participants. fMRI data revealed that personal
      involvement was associated with activation in BA44. Since this brain region is
      known to be involved in semantic memory, the results of this pilot study suggest
      that high involvement consumer behavior may be linked to cognitive load and
      attention towards a product. 

PMID- 25859201
TI  - A computerized tablet with visual feedback of hand position for functional
      magnetic resonance imaging.
AB  - Neuropsychological tests behavioral tasks that very commonly involve handwriting
      and drawing are widely used in the clinic to detect abnormal brain function.
      Functional magnetic resonance imaging (fMRI) may be useful in increasing the
      specificity of such tests. However, performing complex pen-and-paper tests during
      fMRI involves engineering challenges. Previously, we developed an fMRI
      compatible, computerized tablet system to address this issue. However, the tablet
      did not include visual feedback of hand position (VFHP), a human factors
      component that may be important for fMRI of certain patient populations. A real
      time system was thus developed to provide VFHP and integrated with the tablet in
      an augmented reality display. The effectiveness of the system was initially
      tested in young healthy adults who performed various handwriting tasks in front
      of a computer display with and without VFHP. Pilot fMRI of writing tasks were
      performed by two representative individuals with and without VFHP. Quantitative
      analysis of the behavioral results indicated improved writing performance with
      VFHP. The pilot fMRI results suggest that writing with VFHP requires less neural
      resources compared to the without VFHP condition, to maintain similar behavior.
      Thus, the tablet system with VFHP is recommended for future fMRI studies
      involving patients with impaired brain function and where ecologically valid
      behavior is important. 

PMID- 25859203
TI  - Mothers say "baby" and their newborns do not choose to listen: a behavioral
      preference study to compare with ERP results.
AB  - Previously published results from neonatal brain evoked response potential (ERP)
      experiments revealed different brain responses to the single word "baby"
      depending on whether it was recorded by the mother or an unfamiliar female. These
      results are consistent with behavioral preference studies in which infants
      altered pacifier sucking to contingently activate recordings of the maternal vs.
      an unfamiliar female voice, but the speech samples were much longer and
      information-rich than in the ERP studies. Both types of neonatal voice
      recognition studies imply postnatal retention of prenatal learning. The
      preference studies require infant motor and motivation systems to mount a
      response in addition to voice recognition. The current contingent sucking
      preference study was designed to test neonatal motivation to alter behavior when
      the reward is the single word "baby" recorded by the mother or an unfamiliar
      speaker. Results showed an absent or weak contingent sucking response to the
      brief maternal voice sample, and they demonstrate the complementary value of
      electrophysiological and behavioral studies for very early development. Neonates
      can apparently recognize the maternal voice in brief recorded sample (previous
      ERP results) but they are not sufficiently motivated by it to alter sucking
      behavior. 

PMID- 25859202
TI  - Multivariate cross-classification: applying machine learning techniques to
      characterize abstraction in neural representations.
AB  - Here we highlight an emerging trend in the use of machine learning classifiers to
      test for abstraction across patterns of neural activity. When a classifier
      algorithm is trained on data from one cognitive context, and tested on data from
      another, conclusions can be drawn about the role of a given brain region in
      representing information that abstracts across those cognitive contexts. We call
      this kind of analysis Multivariate Cross-Classification (MVCC), and review
      several domains where it has recently made an impact. MVCC has been important in
      establishing correspondences among neural patterns across cognitive domains,
      including motor-perception matching and cross-sensory matching. It has been used
      to test for similarity between neural patterns evoked by perception and those
      generated from memory. Other work has used MVCC to investigate the similarity of
      representations for semantic categories across different kinds of stimulus
      presentation, and in the presence of different cognitive demands. We use these
      examples to demonstrate the power of MVCC as a tool for investigating neural
      abstraction and discuss some important methodological issues related to its
      application. 

PMID- 25859204
TI  - Error-related potentials during continuous feedback: using EEG to detect errors
      of different type and severity.
AB  - When a person recognizes an error during a task, an error-related potential
      (ErrP) can be measured as response. It has been shown that ErrPs can be
      automatically detected in tasks with time-discrete feedback, which is widely
      applied in the field of Brain-Computer Interfaces (BCIs) for error correction or
      adaptation. However, there are only a few studies that concentrate on ErrPs
      during continuous feedback. With this study, we wanted to answer three different
      questions: (i) Can ErrPs be measured in electroencephalography (EEG) recordings
      during a task with continuous cursor control? (ii) Can ErrPs be classified using
      machine learning methods and is it possible to discriminate errors of different
      origins? (iii) Can we use EEG to detect the severity of an error? To answer these
      questions, we recorded EEG data from 10 subjects during a video game task and
      investigated two different types of error (execution error, due to inaccurate
      feedback; outcome error, due to not achieving the goal of an action). We analyzed
      the recorded data to show that during the same task, different kinds of error
      produce different ErrP waveforms and have a different spectral response. This
      allows us to detect and discriminate errors of different origin in an event
      locked manner. By utilizing the error-related spectral response, we show that
      also a continuous, asynchronous detection of errors is possible. Although the
      detection of error severity based on EEG was one goal of this study, we did not
      find any significant influence of the severity on the EEG. 

PMID- 25859205
TI  - Evolutionary aspects of self- and world consciousness in vertebrates.
AB  - Although most aspects of world and self-consciousness are inherently subjective,
      neuroscience studies in humans and non-human animals provide correlational and
      causative indices of specific links between brain activity and representation of
      the self and the world. In this article we review neuroanatomic,
      neurophysiological and neuropsychological data supporting the hypothesis that
      different levels of self and world representation in vertebrates rely upon (i) a
      "basal" subcortical system that includes brainstem, hypothalamus and central
      thalamic nuclei and that may underpin the primary (or anoetic) consciousness
      likely present in all vertebrates; and (ii) a forebrain system that include the
      medial and lateral structures of the cerebral hemispheres and may sustain the
      most sophisticated forms of consciousness [e.g., noetic (knowledge based) and
      autonoetic, reflective knowledge]. We posit a mutual, bidirectional functional
      influence between these two major brain circuits. We conclude that basic aspects
      of consciousness like primary self and core self (based on anoetic and noetic
      consciousness) are present in many species of vertebrates and that, even self
      consciousness (autonoetic consciousness) does not seem to be a prerogative of
      humans and of some non-human primates but may, to a certain extent, be present in
      some other mammals and birds. 

PMID- 25859206
TI  - Shaping pseudoneglect with transcranial cerebellar direct current stimulation and
      music listening.
AB  - Non-invasive brain stimulation modulates cortical excitability depending on the
      initial activation state of the structure being stimulated. Combination of
      cognitive with neurophysiological stimulations has been successfully employed to
      modulate responses of specific brain regions. The present research combined a
      neurophysiological pre-conditioning with a cognitive conditioning stimulation to
      modulate behavior. We applied this new state-dependency approach to investigate
      the cerebellar role in musical and spatial information processing, given that a
      link between musical perception and visuo-spatial abilities and a clear
      cerebellar involvement in music perception and visuo-spatial tasks have been
      reported. Cathodal, anodal or sham transcranial cerebellar Direct Current
      Stimulation (tcDCS) pre-conditioning was applied on the left cerebellar
      hemisphere followed by conditioning stimulation through music or white noise
      listening in a sample of healthy subjects performing a Line Bisection Task (LBT).
      The combination of the cathodal stimulation with music listening resulted in a
      marked attentional shift toward the right hemispace, compensating thus the
      natural leftward bias of the baseline condition (pseudoneglect). Conversely, the
      anodal or sham pre-conditioning stimulations combined with either music and white
      noise conditioning listening did not modulate spatial attention. The efficacy of
      the combined stimulation (cathodal pre-conditioning and music conditioning) and
      the absence of any effect of the single stimulations provide a strong support to
      the state-dependency theory. They propose that tcDCS in combination with music
      listening could act as a rehabilitative tool to improve cognitive functions in
      the presence of neglect or other spatial disorders. 

PMID- 25859207
TI  - The first 1000 days of the autistic brain: a systematic review of diffusion
      imaging studies.
AB  - There is overwhelming evidence that autism spectrum disorder (ASD) is related to
      altered brain connectivity. While these alterations are starting to be well
      characterized in subjects where the clinical picture is fully expressed, less is
      known on their earlier developmental course. In the present study we
      systematically reviewed current knowledge on structural connectivity in ASD
      infants and toddlers. We searched PubMed and Medline databases for all English
      language papers, published from year 2000, exploring structural connectivity in
      populations of infants and toddlers whose mean age was below 30 months. Of the
      264 papers extracted, four were found to be eligible and were reviewed. Three of
      the four selected studies reported higher fractional anisotropy values in
      subjects with ASD compared to controls within commissural fibers, projections
      fibers, and association fibers, suggesting brain hyper-connectivity in the
      earliest phases of the disorder. Similar conclusions emerged from the other
      diffusion parameters assessed. These findings are reversed to what is generally
      found in studies exploring older patient groups and suggest a developmental
      course characterized by a shift toward hypo-connectivity starting at a time
      between two and four years of age. 

PMID- 25859208
TI  - Differences between kinematic synergies and muscle synergies during two-digit
      grasping.
AB  - The large number of mechanical degrees of freedom of the hand is not fully
      exploited during actual movements such as grasping. Usually, angular movements in
      various joints tend to be coupled, and EMG activities in different hand muscles
      tend to be correlated. The occurrence of covariation in the former was termed
      kinematic synergies, in the latter muscle synergies. This study addresses two
      questions: (i) Whether kinematic and muscle synergies can simultaneously
      accommodate for kinematic and kinetic constraints. (ii) If so, whether there is
      an interrelation between kinematic and muscle synergies. We used a reach-grasp
      and-pull paradigm and recorded the hand kinematics as well as eight surface EMGs.
      Subjects had to either perform a precision grip or side grip and had to modify
      their grip force in order to displace an object against a low or high load. The
      analysis was subdivided into three epochs: reach, grasp-and-pull, and static
      hold. Principal component analysis (PCA, temporal or static) was performed
      separately for all three epochs, in the kinematic and in the EMG domain. PCA
      revealed that (i) Kinematic- and muscle-synergies can simultaneously accommodate
      kinematic (grip type) and kinetic task constraints (load condition). (ii)
      Upcoming grip and load conditions of the grasp are represented in kinematic- and
      muscle-synergies already during reach. Phase plane plots of the principal muscle
      synergy against the principal kinematic synergy revealed (iii) that the muscle
      synergy is linked (correlated, and in phase advance) to the kinematic synergy
      during reach and during grasp-and-pull. Furthermore (iv), pair-wise correlations
      of EMGs during hold suggest that muscle-synergies are (in part) implemented by
      coactivation of muscles through common input. Together, these results suggest
      that kinematic synergies have (at least in part) their origin not just in
      muscular activation, but in synergistic muscle activation. In short: kinematic
      synergies may result from muscle synergies. 

PMID- 25859209
TI  - Processing changes when listening to foreign-accented speech.
AB  - This study investigates the mechanisms responsible for fast changes in processing
      foreign-accented speech. Event Related brain Potentials (ERPs) were obtained
      while native speakers of Spanish listened to native and foreign-accented speakers
      of Spanish. We observed a less positive P200 component for foreign-accented
      speech relative to native speech comprehension. This suggests that the extraction
      of spectral information and other important acoustic features was hampered during
      foreign-accented speech comprehension. However, the amplitude of the N400
      component for foreign-accented speech comprehension decreased across the
      experiment, suggesting the use of a higher level, lexical mechanism. Furthermore,
      during native speech comprehension, semantic violations in the critical words
      elicited an N400 effect followed by a late positivity. During foreign-accented
      speech comprehension, semantic violations only elicited an N400 effect. Overall,
      our results suggest that, despite a lack of improvement in phonetic
      discrimination, native listeners experience changes at lexical-semantic levels of
      processing after brief exposure to foreign-accented speech. Moreover, these
      results suggest that lexical access, semantic integration and linguistic re
      analysis processes are permeable to external factors, such as the accent of the
      speaker. 

PMID- 25859210
TI  - Corrigendum "fNIRS-based brain-computer interfaces: a review".
AB  - [This corrects the article on p. 3 in vol. 9, PMID: 25674060.]. 

PMID- 25859211
TI  - Competition improves robustness against loss of information.
AB  - A substantial number of works have aimed at modeling the receptive field
      properties of the primary visual cortex (V1). Their evaluation criterion is
      usually the similarity of the model response properties to the recorded responses
      from biological organisms. However, as several algorithms were able to
      demonstrate some degree of similarity to biological data based on the existing
      criteria, we focus on the robustness against loss of information in the form of
      occlusions as an additional constraint for better understanding the algorithmic
      level of early vision in the brain. We try to investigate the influence of
      competition mechanisms on the robustness. Therefore, we compared four methods
      employing different competition mechanisms, namely, independent component
      analysis, non-negative matrix factorization with sparseness constraint,
      predictive coding/biased competition, and a Hebbian neural network with lateral
      inhibitory connections. Each of those methods is known to be capable of
      developing receptive fields comparable to those of V1 simple-cells. Since
      measuring the robustness of methods having simple-cell like receptive fields
      against occlusion is difficult, we measure the robustness using the
      classification accuracy on the MNIST hand written digit dataset. For this we
      trained all methods on the training set of the MNIST hand written digits dataset
      and tested them on a MNIST test set with different levels of occlusions. We
      observe that methods which employ competitive mechanisms have higher robustness
      against loss of information. Also the kind of the competition mechanisms plays an
      important role in robustness. Global feedback inhibition as employed in
      predictive coding/biased competition has an advantage compared to local lateral
      inhibition learned by an anti-Hebb rule. 

PMID- 25859213
TI  - Neuroinformatics and the The Insight ToolKit.

PMID- 25859214
TI  - AuthorSynth: a collaboration network and behaviorally-based visualization tool of
      activation reports from the neuroscience literature.
AB  - Targeted collaboration is becoming more challenging with the ever-increasing
      number of publications, conferences, and academic responsibilities that the
      modern-day researcher must synthesize. Specifically, the field of neuroimaging
      had roughly 10,000 new papers in PubMed for the year 2013, presenting tens of
      thousands of international authors, each a potential collaborator working on some
      sub-domain in the field. To remove the burden of synthesizing an entire corpus of
      publications, talks, and conference interactions to find and assess
      collaborations, we combine meta-analytical neuroimaging informatics methods with
      machine learning and network analysis toward this goal. We present "AuthorSynth,"
      a novel application prototype that includes (1) a collaboration network to
      identify researchers with similar results reported in the literature; and (2) a
      2D plot-"brain lattice"-to visually summarize a single author's contribution to
      the field, and allow for searching of authors based on behavioral terms. This
      method capitalizes on intelligent synthesis of the neuroimaging literature, and
      demonstrates that data-driven approaches can be used to confirm existing
      collaborations, reveal potential ones, and identify gaps in published knowledge.
      We believe this tool exemplifies how methods from neuroimaging informatics can
      better inform researchers about progress and knowledge in the field, and enhance
      the modern workflow of finding collaborations. 

PMID- 25859212
TI  - Characterizing psychological dimensions in non-pathological subjects through
      autonomic nervous system dynamics.
AB  - The objective assessment of psychological traits of healthy subjects and
      psychiatric patients has been growing interest in clinical and bioengineering
      research fields during the last decade. Several experimental evidences strongly
      suggest that a link between Autonomic Nervous System (ANS) dynamics and specific
      dimensions such as anxiety, social phobia, stress, and emotional regulation might
      exist. Nevertheless, an extensive investigation on a wide range of psycho
      cognitive scales and ANS non-invasive markers gathered from standard and non
      linear analysis still needs to be addressed. In this study, we analyzed the
      discerning and correlation capabilities of a comprehensive set of ANS features
      and psycho-cognitive scales in 29 non-pathological subjects monitored during
      resting conditions. In particular, the state of the art of standard and non
      linear analysis was performed on Heart Rate Variability, InterBreath Interval
      series, and InterBeat Respiration series, which were considered as monovariate
      and multivariate measurements. Experimental results show that each ANS feature is
      linked to specific psychological traits. Moreover, non-linear analysis
      outperforms the psychological assessment with respect to standard analysis.
      Considering that the current clinical practice relies only on subjective scores
      from interviews and questionnaires, this study provides objective tools for the
      assessment of psychological dimensions. 

PMID- 25859215
TI  - Are AD-Typical Regions the Convergence Point of Multiple Pathologies?

PMID- 25859217
TI  - Whole genome sequencing in pharmacogenomics.
AB  - Pharmacogenomics aims to shed light on the role of genes and genomic variants in
      clinical treatment response. Although, several drug-gene relationships are
      characterized to date, many challenges still remain toward the application of
      pharmacogenomics in the clinic; clinical guidelines for pharmacogenomic testing
      are still in their infancy, whereas the emerging high throughput genotyping
      technologies produce a tsunami of new findings. Herein, the potential of whole
      genome sequencing on pharmacogenomics research and clinical application are
      highlighted. 

PMID- 25859216
TI  - New perspectives in signaling mediated by receptors coupled to stimulatory G
      protein: the emerging significance of cAMP efflux and extracellular cAMP
      adenosine pathway.
AB  - G protein-coupled receptors (GPCRs) linked to stimulatory G (Gs) proteins
      (GsPCRs) mediate increases in intracellular cyclic AMP as consequence of
      activation of nine adenylyl cyclases , which differ considerably in their
      cellular distribution and activation mechanisms. Once produced, cyclic AMP may
      act via distinct intracellular signaling effectors such as protein kinase A and
      the exchange proteins activated by cAMP (Epacs). More recently, attention has
      been focused on the efflux of cAMP through a specific transport system named
      multidrug resistance proteins that belongs to the ATP-binding cassette
      transporter superfamily. Outside the cell, cAMP is metabolized into adenosine,
      which is able to activate four distinct subtypes of adenosine receptors, members
      of the GPCR family: A1, A2A, A2B, and A3. Taking into account that this
      phenomenon occurs in numerous cell types, as consequence of GsPCR activation and
      increment in intracellular cAMP levels, in this review, we will discuss the
      impact of cAMP efflux and the extracellular cAMP-adenosine pathway on the
      regulation of GsPCR-induced cell response. 

PMID- 25859218
TI  - A clinician's perspective of the role of renal sympathetic nerves in
      hypertension.
AB  - The renal sympathetic nerves have significant contribution to the control of
      different aspects of kidney function. Early animal studies of renal denervation
      in a large number of different models of hypertension showed that that RDN
      improved BP control. Recently, data from prospective cohorts and randomized
      studies showed that renal denervation therapy (RDN) is a safe procedure but is
      associated with only modest reduction of ambulatory blood pressure (BP) in
      patients on intensive medical therapy. The main goal of this article is to review
      the results of preclinical and clinical studies on the contribution of the renal
      sympathetic nervous system to hypertension and the therapeutic applications of
      catheter-based renal denervation. 

PMID- 25859219
TI  - The importance of Ca(2+)-dependent mechanisms for the initiation of the
      heartbeat.
AB  - Mechanisms underlying pacemaker activity in the sinus node remain controversial,
      with some ascribing a dominant role to timing events in the surface membrane
      ("membrane clock") and others to uptake and release of calcium from the
      sarcoplasmic reticulum (SR) ("calcium clock"). Here we discuss recent evidence on
      mechanisms underlying pacemaker activity with a particular emphasis on the many
      roles of calcium. There are particular areas of controversy concerning the
      contribution of calcium spark-like events and the importance of I(f) to
      spontaneous diastolic depolarisation, though it will be suggested that neither of
      these is essential for pacemaking. Sodium-calcium exchange (NCX) is most often
      considered in the context of mediating membrane depolarisation after spark-like
      events. We present evidence for a broader role of this electrogenic exchanger
      which need not always depend upon these spark-like events. Short (milliseconds or
      seconds) and long (minutes) term influences of calcium are discussed including
      direct regulation of ion channels and NCX, and control of the activity of calcium
      dependent enzymes (including CaMKII, AC1, and AC8). The balance between the many
      contributory factors to pacemaker activity may well alter with experimental and
      clinical conditions, and potentially redundant mechanisms are desirable to ensure
      the regular spontaneous heart rate that is essential for life. This review
      presents evidence that calcium is central to the normal control of pacemaking
      across a range of temporal scales and seeks to broaden the accepted description
      of the "calcium clock" to cover these important influences. 

PMID- 25859221
TI  - The involvement of TRPC3 channels in sinoatrial arrhythmias.
AB  - Atrial fibrillation (AF) is a significant contributor to cardiovascular morbidity
      and mortality. The currently available treatments are limited and AF continues to
      be a major clinical challenge. Clinical studies have shown that AF is frequently
      associated with dysfunction in the sino-atrial node (SAN). The association
      between AF and SAN dysfunction is probably related to the communication between
      the SAN and the surrounding atrial cells that form the SAN-atrial pacemaker
      complex and/or pathological processes that affect both the SAN and atrial
      simultaneously. Recent evidence suggests that Ca(2+) entry through TRPC3
      (Transient Receptor Potential Canonical-3) channels may underlie several
      pathophysiological conditions -including cardiac arrhythmias. However, it is
      still not known if atrial and sinoatrial node cells are also involved. In this
      article we will first briefly review TRPC3 and IP3R signaling that relate to
      store/receptor-operated Ca(2+) entry (SOCE/ROCE) mechanisms and cardiac
      arrhythmias. We will then present some of our recent research progress in this
      field. Our experiments results suggest that pacing-induced AF in angiotensin II
      (Ang II) treated mice are significantly reduced in mice lacking the TRPC3 gene
      (TRPC3(-/-) mice) compared to wild type controls. We also show that pacemaker
      cells express TRPC3 and several other molecular components related to SOCE/ROCE
      signaling, including STIM1 and IP3R. Activation of G-protein coupled receptors
      (GPCRs) signaling that is able to modulate SOCE/ROCE and Ang II induced Ca(2+)
      homeostasis changes in sinoatrial complex being linked to TRPC3. The results
      provide new evidence that TRPC3 may play a role in sinoatrial and atrial
      arrhythmias that are caused by GPCRs activation. 

PMID- 25859220
TI  - Lactobacillus species as biomarkers and agents that can promote various aspects
      of vaginal health.
AB  - The human body is colonized by a vast number of microorganisms collectively
      referred to as the human microbiota. One of the main microbiota body sites is the
      female genital tract, commonly dominated by Lactobacillus spp., in approximately
      70% of women. Each individual species can constitute approximately 99% of the
      ribotypes observed in any individual woman. The most frequently isolated species
      are Lactobacillus crispatus, Lactobacillus gasseri, Lactobacillus jensenii and
      Lactobacillus iners. Residing at the port of entry of bacterial and viral
      pathogens, the vaginal Lactobacillus species can create a barrier against
      pathogen invasion since mainly products of their metabolism secreted in the
      cervicovaginal fluid can play an important role in the inhibition of bacterial
      and viral infections. Therefore, a Lactobacillus-dominated microbiota appears to
      be a good biomarker for a healthy vaginal ecosystem. This balance can be rapidly
      altered during processes such as menstruation, sexual activity, pregnancy and
      various infections. An abnormal vaginal microbiota is characterized by an
      increased diversity of microbial species, leading to a condition known as
      bacterial vaginosis. Information on the vaginal microbiota can be gathered from
      the analysis of cervicovaginal fluid, by using the Nugent scoring or the Amsel's
      criteria, or at the molecular level by investigating the number and type of
      Lactobacillus species. However, when translating this to the clinical setting, it
      should be noted that the absence of a Lactobacillus-dominated microbiota does not
      appear to directly imply a diseased condition or dysbiosis. Nevertheless, the
      widely documented beneficial role of vaginal Lactobacillus species demonstrates
      the potential of data on the composition and activity of lactobacilli as
      biomarkers for vaginal health. The substantiation and further validation of such
      biomarkers will allow the design of better targeted probiotic strategies. 

PMID- 25859223
TI  - Mitochondria: hubs of cellular signaling, energetics and redox balance. A rich,
      vibrant, and diverse landscape of mitochondrial research.

PMID- 25859222
TI  - Quantitative trait loci affecting the 3D skull shape and size in mouse and
      prioritization of candidate genes in-silico.
AB  - We describe the first application of high-resolution 3D micro-computed
      tomography, together with 3D landmarks and geometric morphometrics, to map QTL
      responsible for variation in skull shape and size using a backcross between
      C57BL/6J and A/J inbred strains. Using 433 animals, 53 3D landmarks, and 882 SNPs
      from autosomes, we identified seven QTL responsible for the skull size (SCS.qtl)
      and 30 QTL responsible for the skull shape (SSH.qtl). Size, sex, and direction-of
      cross were all significant factors and included in the analysis as covariates.
      All autosomes harbored at least one SSH.qtl, sometimes up to three. Effect sizes
      of SSH.qtl appeared to be small, rarely exceeding 1% of the overall shape
      variation. However, they account for significant amount of variation in some
      specific directions of the shape space. Many QTL have stronger effect on the
      neurocranium than expected from a random vector that will parcellate uniformly
      across the four cranial regions. On the contrary, most of QTL have an effect on
      the palate weaker than expected. Combined interval length of 30 SSH.qtl was about
      315 MB and contained 2476 known protein coding genes. We used a bioinformatics
      approach to filter these candidate genes and identified 16 high-priority
      candidates that are likely to play a role in the craniofacial development and
      disorders. Thus, coupling the QTL mapping approach in model organisms with
      candidate gene enrichment approaches appears to be a feasible way to identify
      high-priority candidates genes related to the structure or tissue of interest. 

PMID- 25859224
TI  - Two dimensional blue native/SDS-PAGE to identify mitochondrial complex I subunits
      modified by 4-hydroxynonenal (HNE).
AB  - The lipid peroxidation product 4-hydroxynonenal (HNE) can form protein-linked HNE
      adducts, thereby impacting protein structure and function. Mitochondrial complex
      I (NADH-ubiquinone oxidoreductase), containing at least 45 subunits in mammalian
      cells, sits in a lipid-rich environment and is thus very susceptible to HNE
      modifications. In this paper, a procedure for the identification of HNE-modified
      complex I subunits is described. Complex I was isolated by first dimensional non
      gradient blue native polyacrylamide gel electrophoresis (BN-PAGE). The isolated
      complex I band, visualized by either Coomassie blue staining or silver staining,
      was further analyzed by second dimensional sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis (SDS-PAGE). HNE-modified proteins were visualized by Western
      blotting probed with anti-HNE antibodies. HNE-positive bands were then excised
      and the proteins contained in them were identified by mass spectrometric peptide
      sequencing. The method was successfully applied for the identification of two
      complex I subunits that showed enhanced HNE-modifications in diabetic kidney
      mitochondria. 

PMID- 25859225
TI  - Odyssey of human dental pulp stem cells and their remarkable ability to survive
      in extremely adverse conditions.

PMID- 25859227
TI  - Surrogate utility estimation by long-term partners and unfamiliar dyads.
AB  - To what extent are people able to make predictions about other people's
      preferences and values?We report two experiments that present a novel method
      assessing some of the basic processes in surrogate decision-making, namely
      surrogate-utility estimation. In each experiment participants formed dyads who
      were asked to assign utilities to health related items and commodity items, and
      to predict their partner's utility judgments for the same items. In experiment
      one we showed that older adults in long-term relationships were able to
      accurately predict their partner's wishes. In experiment two we showed that
      younger adults who were relatively unfamiliar with one another were also able to
      predict other people's wishes. Crucially we demonstrated that these judgments
      were accurate even after partialling out each participant's own preferences
      indicating that in order to make surrogate utility estimations people engage in
      perspective-taking rather than simple anchoring and adjustment, suggesting that
      utility estimation is not the cause of inaccuracy in surrogate decision-making.
      The data and implications are discussed with respect to theories of surrogate
      decision-making. 

PMID- 25859228
TI  - Perception of speech rhythm in second language: the case of rhythmically similar
      L1 and L2.
AB  - We investigated the perception of developmental changes in timing patterns that
      happen in the course of second language (L2) acquisition, provided that the
      native and the target languages of the learner are rhythmically similar (German
      and English). It was found that speech rhythm in L2 English produced by German
      learners becomes increasingly stress-timed as acquisition progresses. This
      development is captured by the tempo-normalized rhythm measures of durational
      variability. Advanced learners also deliver speech at a faster rate. However,
      when native speakers have to classify the timing patterns characteristic of L2
      English of German learners at different proficiency levels, they attend to speech
      rate cues and ignore the differences in speech rhythm. 

PMID- 25859226
TI  - Role of the endogenous cannabinoid system in nicotine addiction: novel insights.
AB  - Several lines of evidence have shown that the endogenous cannabinoids are
      implicated in several neuropsychiatric diseases. Notably, preclinical and human
      clinical studies have shown a pivotal role of the cannabinoid system in nicotine
      addiction. The CB1 receptor inverse agonist/antagonist rimonabant (also known as
      SR141716) was effective to decrease nicotine-taking and nicotine-seeking in
      rodents, as well as the elevation of dopamine induced by nicotine in brain reward
      area. Rimonabant has been shown to improve the ability of smokers to quit smoking
      in randomized clinical trials. However, rimonabant was removed from the market
      due to increased risk of psychiatric side-effects observed in humans. Recently,
      other components of the endogenous cannabinoid system have been explored. Here,
      we present the recent advances on the understanding of the role of the different
      components of the cannabinoid system on nicotine's effects. Those recent findings
      suggest possible alternative ways of modulating the cannabinoid system that could
      have implication for nicotine dependence treatment. 

PMID- 25859229
TI  - Dimensions of emotional intelligence related to physical and mental health and to
      health behaviors.
AB  - In this paper the relationship between emotional intelligence (EI) and health is
      examined. The current work investigated the dimensions of EI are sufficient to
      explain various components of physical and mental health, and various categories
      of health-related behaviors. A sample of 855 participants completed two measures
      of EI, the Trait Meta-Mood Scale and trait emotional intelligence questionnaire,
      a measure of health, the Health Survey SF-36 Questionnaire (SF-36); and a measure
      of health-related behaviors, the health behavior checklist. The results show that
      the EI dimensions analyzed are better predictors of mental health than of
      physical health. The EI dimensions that positively explain the Mental Health
      Component are Well-Being, Self-Control and Sociability, and negatively,
      Attention. Well-Being, Self-Control and Sociability positively explain the
      Physical Health Component. EI dimensions predict a lower percentage of health
      related behaviors than they do health components. Emotionality and Repair predict
      the Preventive Health Behavior category, and only one dimension, Self-Control,
      predicts the Risk Taking Behavior category. Older people carry out more
      preventive behaviors for health. 

PMID- 25859230
TI  - Complexities of emotional responses to social and non-social affective stimuli in
      schizophrenia.
AB  - BACKGROUND: Adaptive emotional responses are important in interpersonal
      relationships. We investigated self-reported emotional experience, physiological
      reactivity, and micro-facial expressivity in relation to the social nature of
      stimuli in individuals with schizophrenia (SZ). METHOD: Galvanic skin response
      (GSR) and facial electromyography (fEMG) were recorded in medicated outpatients
      with SZ and demographically matched healthy controls (CO) while they viewed
      social and non-social images from the International Affective Pictures System.
      Participants rated the valence and arousal, and selected a label for experienced
      emotions. Symptom severity in the SZ and psychometric schizotypy in CO were
      assessed. RESULTS: The two groups did not differ in their labeling of the
      emotions evoked by the stimuli, but individuals with SZ were more positive in
      their valence ratings. Although self-reported arousal was similar in both groups,
      mean GSR was greater in SZ, suggesting differential awareness, or calibration of
      internal states. Both groups reported social images to be more arousing than non
      social images but their physiological responses to non-social vs. social images
      were different. Self-reported arousal to neutral social images was correlated
      with positive symptoms in SZ. Negative symptoms in SZ and disorganized schizotypy
      in CO were associated with reduced mean fEMG. Greater corrugator mean fEMG
      activity for positive images in SZ indicates valence-incongruent facial
      expressions. CONCLUSION: The patterns of emotional responses differed between the
      two groups. While both groups were in broad agreement in self-reported arousal
      and emotion labels, their mean GSR, and fEMG correlates of emotion diverged in
      relation to the social nature of the stimuli and clinical measures. Importantly,
      these results suggest disrupted self awareness of internal states in SZ and
      underscore the complexities of emotion processing in health and disease.

PMID- 25859231
TI  - Imagining the impossible before breakfast: the relation between creativity,
      dissociation, and sleep.
AB  - Dissociative symptoms have been related to higher rapid eye movement sleep
      density, a sleep phase during which hyperassociativity may occur. This may
      enhance artistic creativity during the day. To test this hypothesis, we conducted
      a creative photo contest to explore the relation between dissociation, sleep, and
      creativity. During the contest, participants (N = 72) took one photo per day for
      five consecutive days, based on specific daily themes (consisting of single
      words) and the instruction to take as creative a photo as possible each day.
      Furthermore, they completed daily measures of state dissociation and a short
      sleep diary. The photos and their captions were ranked by two professional
      photographers and two clinical psychologists based on creativity, originality,
      bizarreness, and quality. We expected that dissociative people would rank higher
      in the contest compared with low-dissociative participants, and that the most
      original photos would be taken on days when the participants scored highest on
      acute dissociation. We found that acute dissociation predicted a higher ranking
      on creativity. Poorer sleep quality and fewer hours of sleep predicted more
      bizarreness in the photos and captions. None of the trait measures could predict
      creativity. In sum, acute dissociation related to enhanced creativity. These
      findings contribute to our understanding of dissociative symptomatology. 

PMID- 25859232
TI  - Cognitive skills and reading in adults with Usher syndrome type 2.
AB  - OBJECTIVE: To investigate working memory (WM), phonological skills, lexical
      skills, and reading comprehension in adults with Usher syndrome type 2 (USH2).
      DESIGN: The participants performed tests of phonological processing, lexical
      access, WM, and reading comprehension. The design of the test situation and tests
      was specifically considered for use with persons with low vision in combination
      with hearing impairment. The performance of the group with USH2 on the different
      cognitive measures was compared to that of a matched control group with normal
      hearing and vision (NVH). STUDY SAMPLE: Thirteen participants with USH2 aged 21
      60 years and a control group of 10 individuals with NVH, matched on age and level
      of education. RESULTS: The group with USH2 displayed significantly lower
      performance on tests of phonological processing, and on measures requiring both
      fast visual judgment and phonological processing. There was a larger variation in
      performance among the individuals with USH2 than in the matched control group.
      CONCLUSION: The performance of the group with USH2 indicated similar problems
      with phonological processing skills and phonological WM as in individuals with
      long-term hearing loss. The group with USH2 also had significantly longer
      reaction times, indicating that processing of visual stimuli is difficult due to
      the visual impairment. These findings point toward the difficulties in accessing
      information that persons with USH2 experience, and could be part of the
      explanation of why individuals with USH2 report high levels of fatigue and
      feelings of stress (Wahlqvist et al., 2013).

PMID- 25859233
TI  - Intra-individual variability and continuity of action and perception measures in
      infants.
AB  - The development of action and perception, and their relation in infancy is a
      central research area in socio-cognitive sciences. In this Perspective Article,
      we focus on the developmental variability and continuity of action and
      perception. At group level, these skills have been shown to consistently improve
      with age. We would like to raise awareness for the issue that, at individual
      level, development might be subject to more variable changes. We present data
      from a longitudinal study on the perception and production of contralateral
      reaching skills of infants aged 7, 8, 9, and 12 months. Our findings suggest that
      individual development does not increase linearly for action or for perception,
      but instead changes dynamically. These non-continuous changes substantially
      affect the relation between action and perception at each measuring point and the
      respective direction of causality. This suggests that research on the development
      of action and perception and their interrelations needs to take into account
      individual variability and continuity more progressively. 

PMID- 25859235
TI  - Spatial complexity of character-based writing systems and arithmetic in primary
      school: a longitudinal study.
AB  - Previous research has consistently found an association between spatial and
      mathematical abilities. We hypothesized that this link may partially explain the
      consistently observed advantage in mathematics demonstrated by East Asian
      children. Spatial complexity of the character-based writing systems may reflect
      or lead to a cognitive advantage relevant to mathematics. Seven hundered and
      twenty one 6-9-year old children from the UK and Russia were assessed on a
      battery of cognitive skills and arithmetic. The Russian children were recruited
      from specialist linguistic schools and divided into four different language
      groups, based on the second language they were learning (i.e., English, Spanish,
      Chinese, and Japanese). The UK children attended regular schools and were not
      learning any second language. The testing took place twice across the school
      year, once at the beginning, before the start of the second language acquisition,
      and once at the end of the year. The study had two aims: (1) to test whether
      spatial ability predicts mathematical ability in 7-9 year-old children across the
      samples; (2) to test whether acquisition and usage of a character-based writing
      system leads to an advantage in performance in arithmetic and related cognitive
      tasks. The longitudinal link from spatial ability to mathematics was found only
      in the Russian sample. The effect of second language acquisition on mathematics
      or other cognitive skills was negligible, although some effect of Chinese
      language on mathematical reasoning was suggested. Overall, the findings suggest
      that although spatial ability is related to mathematics at this age, one academic
      year of exposure to spatially complex writing systems is not enough to provide a
      mathematical advantage. Other educational and socio-cultural factors might play a
      greater role in explaining individual and cross-cultural differences in
      arithmetic at this age. 

PMID- 25859236
TI  - Chronologically organized structure in autobiographical memory search.
AB  - Each of us has a rich set of autobiographical memories that provides us with a
      coherent story of our lives. These memories are known to be highly structured
      both thematically and temporally. However, it is not known how we naturally tend
      to explore the mental timeline of our memories. Here we developed a novel cued
      retrieval paradigm in order to investigate the temporal element of memory search.
      We found that, when asked to search for memories in the days immediately
      surrounding a salient cued event, participants displayed a marked set of temporal
      biases in their search patterns. Specifically, participants first tended to jump
      back in time and retrieve memories from the day prior to the cued event.
      Following this they then transitioned forward in time, and retrieved memories
      from the day after the cued event. This pattern of results replicated in a second
      experiment with a much larger group of participants, and a different method of
      cueing the memories. We argue that this set of temporal biases is consistent with
      memory search conforming to a temporally ordered narrative structure. 

PMID- 25859237
TI  - When seeing is learning: dynamic and interactive visualizations to teach
      statistical concepts.

PMID- 25859234
TI  - Advancing understanding of executive function impairments and psychopathology:
      bridging the gap between clinical and cognitive approaches.
AB  - Executive function (EF) is essential for successfully navigating nearly all of
      our daily activities. Of critical importance for clinical psychological science,
      EF impairments are associated with most forms of psychopathology. However,
      despite the proliferation of research on EF in clinical populations, with notable
      exceptions clinical and cognitive approaches to EF have remained largely
      independent, leading to failures to apply theoretical and methodological advances
      in one field to the other field and hindering progress. First, we review the
      current state of knowledge of EF impairments associated with psychopathology and
      limitations to the previous research in light of recent advances in understanding
      and measuring EF. Next, we offer concrete suggestions for improving EF
      assessment. Last, we suggest future directions, including integrating modern
      models of EF with state of the art, hierarchical models of dimensional
      psychopathology as well as translational implications of EF-informed research on
      clinical science. 

PMID- 25859238
TI  - Angry facial expressions bias gender categorization in children and adults:
      behavioral and computational evidence.
AB  - Angry faces are perceived as more masculine by adults. However, the developmental
      course and underlying mechanism (bottom-up stimulus driven or top-down belief
      driven) associated with the angry-male bias remain unclear. Here we report that
      anger biases face gender categorization toward "male" responding in children as
      young as 5-6 years. The bias is observed for both own- and other-race faces, and
      is remarkably unchanged across development (into adulthood) as revealed by signal
      detection analyses (Experiments 1-2). The developmental course of the angry-male
      bias, along with its extension to other-race faces, combine to suggest that it is
      not rooted in extensive experience, e.g., observing males engaging in aggressive
      acts during the school years. Based on several computational simulations of
      gender categorization (Experiment 3), we further conclude that (1) the angry-male
      bias results, at least partially, from a strategy of attending to facial features
      or their second-order relations when categorizing face gender, and (2) any single
      choice of computational representation (e.g., Principal Component Analysis) is
      insufficient to assess resemblances between face categories, as different
      representations of the very same faces suggest different bases for the angry-male
      bias. Our findings are thus consistent with stimulus-and stereotyped-belief
      driven accounts of the angry-male bias. Taken together, the evidence suggests
      considerable stability in the interaction between some facial dimensions in
      social categorization that is present prior to the onset of formal schooling. 

PMID- 25859239
TI  - What is the Optimal Duration of Middle-Cerebral Artery Occlusion Consistently
      Resulting in Isolated Cortical Selective Neuronal Loss in the Spontaneously
      Hypertensive Rat?
AB  - INTRODUCTION AND OBJECTIVES: Selective neuronal loss (SNL) in the reperfused
      penumbra may impact clinical recovery and is thus important to investigate. Brief
      proximal middle cerebral artery occlusion (MCAo) results in predominantly
      striatal SNL, yet cortical damage is more relevant given its behavioral
      implications and that thrombolytic therapy mainly rescues the cortex. Distal
      temporary MCAo (tMCAo) does target the cortex, but the optimal occlusion duration
      that results in isolated SNL has not been determined. In the present study, we
      assessed different distal tMCAo durations looking for consistently pure SNL.
      METHODS: Microclip distal tMCAo (md-tMCAo) was performed in ~6-month old male
      spontaneously hypertensive rats (SHRs). We previously reported that 45 min md
      tMCAo in SHRs results in pan-necrosis in the majority of subjects. Accordingly,
      three shorter MCAo durations were investigated here in decremental succession,
      namely 30, 22, and 15 min (n = 3, 3, and 7 subjects, respectively).
      Recanalization was confirmed by MR angiography just prior to brain collection at
      28 days and T2-weighted MRI was obtained for characterization of ischemic
      lesions. NeuN, OX42, and GFAP immunohistochemistry appraised changes in neurons,
      microglia, and astrocytes, respectively. Ischemic lesions were categorized into
      three main types: (1) pan-necrosis; (2) partial infarction; and (3) SNL. RESULTS:
      Pan-necrosis or partial infarction was present in all 30 min and 22 min subjects,
      but not in the 15 min group (p < 0.001), in which isolated cortical SNL was
      consistently present. MRI revealed characteristic hyperintense abnormalities in
      all rats with pan-necrosis or partial infarction, but no change in any 15 min
      subject. CONCLUSION: We found that 15 min distal MCAo consistently resulted in
      pure cortical SNL, whereas durations equal or longer than 22 min consistently
      resulted in infarcts. This model may be of use to study the pathophysiology of
      cortical SNL and its prevention by appropriate interventions.

PMID- 25859241
TI  - Hypothalamic-pituitary-gonadal axis involvement in learning and memory and
      Alzheimer's disease: more than "just" estrogen.
AB  - Accumulating studies affirm the effects of age-related endocrine dysfunction on
      cognitive decline and increasing risk of neurodegenerative diseases. It is well
      known that estrogens can be protective for cognitive function, and more recently
      androgens and luteinizing hormone have also been shown to modulate learning and
      memory. Understanding the mechanisms underlying hypothalamic-pituitary-gonadal
      axis-associated cognitive dysfunction is crucial for therapeutic advancement.
      Here, we emphasize that reproductive hormones are influential in maintaining
      neuronal health and enhancing signaling cascades that lead to cognitive
      impairment. We summarize and critically evaluate age-related changes in the
      endocrine system, their implications in the development of Alzheimer's disease,
      and the therapeutic potential of endocrine modulation in the prevention of age
      related cognitive decline. 

PMID- 25859240
TI  - Role of non-neuronal cells in body weight and appetite control.
AB  - The brain is composed of neurons and non-neuronal cells, with the latter
      encompassing glial, ependymal and endothelial cells, as well as pericytes and
      progenitor cells. Studies aimed at understanding how the brain operates have
      traditionally focused on neurons, but the importance of non-neuronal cells has
      become increasingly evident. Once relegated to supporting roles, it is now
      indubitable that these diverse cell types are fundamental for brain development
      and function, including that of metabolic circuits, and they may play a
      significant role in obesity onset and complications. They participate in
      processes of neurogenesis, synaptogenesis, and synaptic plasticity of metabolic
      circuits both during development and in adulthood. Some glial cells, such as
      tanycytes and astrocytes, transport circulating nutrients and metabolic factors
      that are fundamental for neuronal viability and activity into and within the
      hypothalamus. All of these cell types express receptors for a variety of
      metabolic factors and hormones, suggesting that they participate in metabolic
      function. They are the first line of defense against any assault to neurons.
      Indeed, microglia and astrocytes participate in the hypothalamic inflammatory
      response to high fat diet (HFD)-induced obesity, with this process contributing
      to inflammatory-related insulin and leptin resistance. Moreover, HFD-induced
      obesity and hyperleptinemia modify hypothalamic astroglial morphology, which is
      associated with changes in the synaptic inputs to neuronal metabolic circuits.
      Astrocytic contact with the microvasculature is increased by HFD intake and this
      could modify nutrient/hormonal uptake into the brain. In addition, progenitor
      cells in the hypothalamus are now known to have the capacity to renew metabolic
      circuits, and this can be affected by HFD intake and obesity. Here, we discuss
      our current understanding of how non-neuronal cells participate in physiological
      and physiopathological metabolic control. 

PMID- 25859242
TI  - No more monkeying around: primate malaria model systems are key to understanding
      Plasmodium vivax liver-stage biology, hypnozoites, and relapses.
AB  - Plasmodium vivax is a human malaria parasite responsible for significant
      morbidity worldwide and potentially death. This parasite possesses formidable
      liver-stage biology that involves the formation of dormant parasites known as
      hypnozoites. Hypnozoites are capable of activating weeks, months, or years after
      a primary blood-stage infection causing relapsing bouts of illness. Elimination
      of this dormant parasitic reservoir will be critical for global malaria
      eradication. Although hypnozoites were first discovered in 1982, few advancements
      have been made to understand their composition and biology. Until recently, in
      vitro models did not exist to study these forms and studying them from human ex
      vivo samples was virtually impossible. Today, non-human primate (NHP) models and
      modern systems biology approaches are poised as tools to enable the in-depth
      study of P. vivax liver-stage biology, including hypnozoites and relapses. NHP
      liver-stage model systems for P. vivax and the related simian malaria species P.
      cynomolgi are discussed along with perspectives regarding metabolite biomarker
      discovery, putative roles of extracellular vesicles, and relapse immunobiology. 

PMID- 25859243
TI  - Hantavirus-induced disruption of the endothelial barrier: neutrophils are on the
      payroll.
AB  - Viral hemorrhagic fever caused by hantaviruses is an emerging infectious disease
      for which suitable treatments are not available. In order to improve this
      situation a better understanding of hantaviral pathogenesis is urgently required.
      Hantaviruses infect endothelial cell layers in vitro without causing any
      cytopathogenic effect and without increasing permeability. This implies that the
      mechanisms underlying vascular hyperpermeability in hantavirus-associated disease
      are more complex and that immune mechanisms play an important role. In this
      review we highlight the latest developments in hantavirus-induced
      immunopathogenesis. A possible contribution of neutrophils has been neglected so
      far. For this reason, we place special emphasis on the pathogenic role of
      neutrophils in disrupting the endothelial barrier. 

PMID- 25859244
TI  - Beyond research: a primer for considerations on using viral metagenomics in the
      field and clinic.
AB  - Powered by recent advances in next-generation sequencing technologies,
      metagenomics has already unveiled vast microbial biodiversity in a range of
      environments, and is increasingly being applied in clinics for difficult-to
      diagnose cases. It can be tempting to suggest that metagenomics could be used as
      a "universal test" for all pathogens without the need to conduct lengthy serial
      testing using specific assays. While this is an exciting prospect, there are
      issues that need to be addressed before metagenomic methods can be applied with
      rigor as a diagnostic tool, including the potential for incidental findings,
      unforeseen consequences for trade and regulatory authorities, privacy and
      cultural issues, data sharing, and appropriate reporting of results to end-users.
      These issues will require consideration and discussion across a range of
      disciplines, with inclusion of scientists, ethicists, clinicians, diagnosticians,
      health practitioners, and ultimately the public. Here, we provide a primer for
      consideration on some of these issues. 

PMID- 25859245
TI  - Spatial variability of microbial assemblages associated with a dominant habitat
      forming seaweed.
AB  - Macroalgal surfaces support abundant and diverse microorganisms within biofilms,
      which are often involved in fundamental functions relating to the health and
      defense of their seaweed hosts, including algal development, facilitation of
      spore release, and chemical antifouling. Given these intimate and important
      interactions, environmental changes have the potential to negatively impact
      macroalgae by disrupting seaweed-microbe interactions. We used the disappearance
      of the dominant canopy-forming fucoid Phyllospora comosa from the metropolitan
      coast of Sydney, NSW, Australia as a model system to study these interactions. We
      transplanted Phyllospora individuals from nearby, extant populations back onto
      reefs in Sydney to test whether bacterial assemblages associated with seaweed
      surfaces would be influenced by (i) the host itself, independently of where it
      occurs, (ii) the type of habitat where the host occurs, or (iii) site-specific
      differences. Analyses of bacterial DNA fingerprints (terminal fragment length
      polymorphisms) indicated that assemblages of bacteria on Phyllospora were not
      habitat-specific. Rather, they were primarily influenced by local, site-specific
      conditions with some evidence for host-specificity in some cases. This could
      suggest a lottery model of host-surface colonization, by which hosts are
      colonized by 'suitable' bacteria available in the local species pool, resulting
      in high variability in assemblage structure across sites, but where some species
      in the community are specific to the host and possibly influenced by differences
      in host traits. 

PMID- 25859246
TI  - Oxidative stress and starvation in Dinoroseobacter shibae: the role of
      extrachromosomal elements.
AB  - Aerobic anoxygenic phototrophic bacteria (AAP) are abundant in the photic zone of
      the marine environment. Dinoroseobacter shibae, a representative of the
      Roseobacter group, converts light into additional energy that enhances its
      survival especially under starvation. However, light exposure results in the
      production of cytotoxic reactive oxygen species in AAPs. Here we investigated the
      response of D. shibae to starvation and oxidative stress, focusing on the role of
      extrachromosomal elements (ECRs). D. shibae possessing five ECRs (three plasmids
      and two chromids) was starved for 4 weeks either in the dark or under light/dark
      cycles and the survival was monitored. Transcriptomics showed that on the
      chromosome genes with a role in oxidative stress response and photosynthesis were
      differentially expressed during the light period. Most extrachromosomal genes in
      contrast showed a general loss of transcriptional activity, especially in dark
      starved cells. The observed decrease of gene expression was not due to plasmid
      loss, as all five ECRs were maintained in the cells. Interestingly, the genes on
      the 72-kb chromid were the least downregulated, and one region with genes of the
      oxygen stress response and a light-dependent protochlorophyllide reductase of
      cyanobacterial origin was strongly activated under the light/dark cycle. A
      Delta72-kb curing mutant lost the ability to survive under starvation in a
      light/dark cycle demonstrating the essential role of this chromid for adaptation
      to starvation and oxidative stress. Our data moreover suggest that the other four
      ECRs of D. shibae have no vital function under the investigated conditions and
      therefore were transcriptionally silenced. 

PMID- 25859247
TI  - Immunotherapy in Cancer: A Combat between Tumors and the Immune System; You Win
      Some, You Lose Some.
AB  - Cancer immunotherapy has emerged as a treatment modality, mainly as the result of
      discoveries in the immune response regulation, including mechanisms that turn off
      immune responses. Immunogenic cutaneous melanoma is a canonical model for
      therapeutic immunotherapy studies. "Passive" immunotherapy with monoclonal
      antibodies (mAbs) has outpaced "active" immunotherapy with anti-tumor vaccines,
      and mAbs that antagonize the off responses have been recently introduced in
      clinical practice. Despite these recent successes, many unresolved practical and
      theoretical questions remain. Notably unknown are the identity of the lymphocytes
      that eliminate tumor cells, which white cells enter into tumors, through which
      endothelium, in what order, and how they perform their task. The parameters of
      size and location that could be used to determine in which tumors the immune
      response may be sufficient to eradicate the tumor are yet unknown. Immunotherapy
      has been so far more efficient to treat solid and hematologic tumors located
      outside the central nervous system, than primary brain tumors and brain
      metastases. In contrast to recent advances with mAbs, anti-tumor vaccine
      development has been lagging behind. The multiplicity of antigens that must be
      targeted to achieve significant clinical response is partially responsible for
      this lag, especially in melanoma, one of the most mutated tumors. Further
      hampering vaccination results is the fact that tumor elimination by the immune
      system is the result of a race between tumors with different growth rates and the
      relatively slow development of the adaptive immune response. The enhancement of
      the native arm of the immune response or the administration of targeted
      chemotherapy to slow tumor development, are approaches that should be studied.
      Finally, criteria used to analyze patient response to immunotherapeutic
      treatments must be perfected, and the patient populations that could benefit the
      most from this approach must be better defined. 

PMID- 25859248
TI  - Apoptotic cell clearance and its role in the origin and resolution of chronic
      inflammation.

PMID- 25859249
TI  - Ice nucleation activity in various tissues of Rhododendron flower buds: their
      relevance to extraorgan freezing.
AB  - Wintering flower buds of cold hardy Rhododendron japonicum cooled slowly to
      subfreezing temperatures are known to undergo extraorgan freezing, whose
      mechanisms remain obscure. We revisited this material to demonstrate why bud
      scales freeze first in spite of their lower water content, why florets remain
      deeply supercooled and how seasonal adaptive responses occur in regard to
      extraorgan freezing in flower buds. We determined ice nucleation activity (INA)
      of various flower bud tissues using a test tube-based assay. Irrespective of
      collection sites, outer and inner bud scales that function as ice sinks in
      extraorgan freezing had high INA levels whilst florets that remain supercooled
      and act as a water source lacked INA. The INA level of bud scales was not high in
      late August when flower bud formation was ending, but increased to reach the
      highest level in late October just before the first autumnal freeze. The results
      support the following hypothesis: the high INA in bud scales functions as the
      subfreezing sensor, ensuring the primary freezing in bud scales at warmer subzero
      temperatures, which likely allows the migration of floret water to the bud scales
      and accumulation of icicles within the bud scales. The low INA in the florets
      helps them remain unfrozen by deep supercooling. The INA in the bud scales was
      resistant to grinding and autoclaving at 121(?)C for 15 min, implying the
      intrinsic nature of the INA rather than of microbial origin, whilst the INA in
      stem bark was autoclaving-labile. Anti-nucleation activity (ANA) was implicated
      in the leachate of autoclaved bud scales, which suppresses the INA at millimolar
      levels of concentration and likely differs from the colligative effects of the
      solutes. The tissue INA levels likely contribute to the establishment of freezing
      behaviors by ensuring the order of freezing in the tissues: from the primary
      freeze to the last tissue remaining unfrozen. 

PMID- 25859250
TI  - How salicylic acid takes transcriptional control over jasmonic acid signaling.
AB  - Transcriptional regulation is a central process in plant immunity. The induction
      or repression of defense genes is orchestrated by signaling networks that are
      directed by plant hormones of which salicylic acid (SA) and jasmonic acid (JA)
      are the major players. Extensive cross-communication between the hormone
      signaling pathways allows for fine tuning of transcriptional programs,
      determining resistance to invaders and trade-offs with plant development. Here,
      we give an overview of how SA can control transcriptional reprogramming of JA
      induced genes in Arabidopsis thaliana. SA can influence activity and/or
      localization of transcriptional regulators by post-translational modifications of
      transcription factors and co-regulators. SA-induced redox changes, mediated by
      thioredoxins and glutaredoxins, modify transcriptional regulators that are
      involved in suppression of JA-dependent genes, such as NPR1 and TGA transcription
      factors, which affects their localization or DNA binding activity. Furthermore,
      SA can mediate sequestering of JA-responsive transcription factors away from
      their target genes by stalling them in the cytosol or in complexes with repressor
      proteins in the nucleus. SA also affects JA-induced transcription by inducing
      degradation of transcription factors with an activating role in JA signaling, as
      was shown for the ERF transcription factor ORA59. Additionally, SA can induce
      negative regulators, among which WRKY transcription factors, that can directly or
      indirectly inhibit JA-responsive gene expression. Finally, at the DNA level,
      modification of histones by SA-dependent factors can result in repression of JA
      responsive genes. These diverse and complex regulatory mechanisms affect
      important signaling hubs in the integration of hormone signaling networks. Some
      pathogens have evolved effectors that highjack hormone crosstalk mechanisms for
      their own good, which are described in this review as well. 

PMID- 25859251
TI  - Genetic diversity in tef [Eragrostis tef (Zucc.) Trotter].
AB  - Tef [Eragrostis tef (Zucc.) Trotter] is a cereal crop resilient to adverse
      climatic and soil conditions, and possessing desirable storage properties.
      Although tef provides high quality food and grows under marginal conditions
      unsuitable for other cereals, it is considered to be an orphan crop because it
      has benefited little from genetic improvement. Hence, unlike other cereals such
      as maize and wheat, the productivity of tef is extremely low. In spite of the low
      productivity, tef is widely cultivated by over six million small-scale farmers in
      Ethiopia where it is annually grown on more than three million hectares of land,
      accounting for over 30% of the total cereal acreage. Tef, a tetraploid with 40
      chromosomes (2n = 4x = 40), belongs to the family Poaceae and, together with
      finger millet (Eleusine coracana Gaerth.), to the subfamily Chloridoideae. It was
      originated and domesticated in Ethiopia. There are about 350 Eragrostis species
      of which E. tef is the only species cultivated for human consumption. At the
      present time, the gene bank in Ethiopia holds over five thousand tef accessions
      collected from geographical regions diverse in terms of climate and elevation.
      These germplasm accessions appear to have huge variability with regard to key
      agronomic and nutritional traits. In order to properly utilize the variability in
      developing new tef cultivars, various techniques have been implemented to catalog
      the extent and unravel the patterns of genetic diversity. In this review, we show
      some recent initiatives investigating the diversity of tef using genomics,
      transcriptomics and proteomics and discuss the prospect of these efforts in
      providing molecular resources that can aid modern tef breeding. 

PMID- 25859252
TI  - Nitrogen uptake and nitrogen fertilizer recovery in old and modern wheat
      genotypes grown in the presence or absence of interspecific competition.
AB  - Choosing genotypes with a high capacity for taking up nitrogen (N) from the soil
      and the ability to efficiently compete with weeds for this nutrient is essential
      to increasing the sustainability of cropping systems that are less dependent on
      auxiliary inputs. This research aimed to verify whether differences exist in N
      uptake and N fertilizer recovery capacity among wheat genotypes and, if so,
      whether these differences are related to a different competitive ability against
      weeds of wheat genotypes. To this end, 12 genotypes, varying widely in
      morphological traits and year of release, were grown in the presence or absence
      of interspecific competition (using Avena sativa L. as a surrogate weed).
      Isotopic tracer (15)N was used to measure the fertilizer N uptake efficiencies of
      the wheat genotypes and weed. A field experiment, a split-plot design with four
      replications, was conducted during two consecutive growing seasons in a typical
      Mediterranean environment. In the absence of interspecific competition, few
      differences in either total N uptake (range: 98-112 kg N ha(-1)) or the (15)N
      fertilizer recovery fraction (range: 30.0-36.7%) were observed among the wheat
      genotypes. The presence of competition, compared to competitor-free conditions,
      resulted in reductions in grain yield (49%), total N uptake (29%), and an (15)N
      fertilizer recovery fraction (32%) that were on average markedly higher in modern
      varieties than in old ones. Both biomass and grain reductions were strongly
      related to the biomass of the competitor (correlation coefficients > 0.95), which
      ranged from 135 to 573 g m(-2). Variations in both grain and biomass yield due to
      interspecific competition were significantly correlated with percentage of soil
      cover and leaf area at tillering, plant height at heading, and total N uptake,
      thus highlighting that the ability to take up N from the soil played a certain
      role in determining the different competitive abilities against weed of the
      genotypes. 

PMID- 25859253
TI  - A systematic simulation of the effect of salicylic acid on sphingolipid
      metabolism.
AB  - The phytohormone salicylic acid (SA) affects plant development and defense
      responses. Recent studies revealed that SA also participates in the regulation of
      sphingolipid metabolism, but the details of this regulation remain to beexplored.
      Here, we use in silico Flux Balance Analysis (FBA) with published microarray data
      to construct a whole-cell simulation model, including 23 pathways, 259 reactions,
      and 172 metabolites, to predict the alterations in flux of major sphingolipid
      species after treatment with exogenous SA. This model predicts significant
      changes in fluxes of certain sphingolipid species after SA treatment, changes
      that likely trigger downstream physiological and phenotypic effects. To validate
      the simulation, we used (15)N-labeled metabolic turnover analysis to measure
      sphingolipid contents and turnover rate in Arabidopsis thaliana seedlings treated
      with SA or the SA analog benzothiadiazole (BTH). The results show that both SA
      and BTH affect sphingolipid metabolism, altering the concentrations of certain
      species and also changing the optimal flux distribution and turnover rate of
      sphingolipids. Our strategy allows us to estimate sphingolipid fluxes on a short
      time scale and gives us a systemic view of the effect of SA on sphingolipid
      homeostasis. 

PMID- 25859254
TI  - Correlation between a loss of auxin signaling and a loss of proliferation in
      maize antipodal cells.
AB  - The plant life cycle alternates between two genetically active generations: the
      diploid sporophyte and the haploid gametophyte. In angiosperms the gametophytes
      are sexually dimorphic and consist of only a few cells. The female gametophyte,
      or embryo sac, is comprised of four cell types: two synergids, an egg cell, a
      central cell, and a variable number of antipodal cells. In some species the
      antipodal cells are indistinct and fail to proliferate, so many aspects of
      antipodal cell function and development have been unclear. In maize and many
      other grasses, the antipodal cells proliferate to produce a highly distinct
      cluster at the chalazal end of the embryo sac that persists at the apex of the
      endosperm after fertilization. The antipodal cells are a site of auxin
      accumulation in the maize embryo sac. Analysis of different families of genes
      involved in auxin biosynthesis, distribution, and signaling for expression in the
      embryo sac demonstrates that all steps are expressed within the embryo sac. In
      contrast to auxin signaling, cytokinin signaling is absent in the embryo sac and
      instead occurs adjacent to but outside of the antipodal cells. Mutant analysis
      shows a correlation between a loss of auxin signaling and a loss of proliferation
      of the antipodal cells. The leaf polarity mutant Laxmidrib1 causes a lack of
      antipodal cell proliferation coupled with a loss of DR5 and PIN1a expression in
      the antipodal cells. 

PMID- 25859255
TI  - Focus issue on plant immunity: from model systems to crop species.

PMID- 25859256
TI  - New insights into how seeds are made.

PMID- 25859258
TI  - Cis-encoded non-coding antisense RNAs in streptococci and other low GC Gram (+)
      bacterial pathogens.
AB  - Due to recent advances of bioinformatics and high throughput sequencing
      technology, discovery of regulatory non-coding RNAs in bacteria has been
      increased to a great extent. Based on this bandwagon, many studies searching for
      trans-acting small non-coding RNAs in streptococci have been performed
      intensively, especially in the important human pathogen, group A and B
      streptococci. However, studies for cis-encoded non-coding antisense RNAs in
      streptococci have been scarce. A recent study shows antisense RNAs are involved
      in virulence gene regulation in group B streptococcus, S. agalactiae. This
      suggests antisense RNAs could have important roles in the pathogenesis of
      streptococcal pathogens. In this review, we describe recent discoveries of
      chromosomal cis-encoded antisense RNAs in streptococcal pathogens and other low
      GC Gram (+) bacteria to provide a guide for future studies. 

PMID- 25859257
TI  - Non-coding RNAs and HIV: viral manipulation of host dark matter to shape the
      cellular environment.
AB  - On October 28th 1943 Winston Churchill said "we shape our buildings, and
      afterward our buildings shape us" (Humes, 1994). Churchill was pondering how and
      when to rebuild the British House of Commons, which had been destroyed by enemy
      bombs on May 10th 1941. The old House had been small and insufficient to hold all
      its members, but was restored to its original form in 1950 in order to recapture
      the "convenience and dignity" that the building had shaped into its parliamentary
      members. The circular loop whereby buildings or dwellings are shaped and go on to
      shape those that reside in them is also true of pathogens and their hosts. As
      obligate parasites, pathogens need to alter their cellular host environments to
      ensure survival. Typically pathogens modify cellular transcription profiles and
      in doing so, the pathogen in turn is affected, thereby closing the loop. As key
      orchestrators of gene expression, non-coding RNAs provide a vast and extremely
      precise set of tools for pathogens to target in order to shape the cellular
      environment. This review will focus on host non-coding RNAs that are manipulated
      by the infamous intracellular pathogen, the human immunodeficiency virus (HIV).
      We will briefly describe both short and long host non-coding RNAs and discuss how
      HIV gains control of these factors to ensure widespread dissemination throughout
      the host as well as the establishment of lifelong, chronic infection. 

PMID- 25859259
TI  - Hippocampal transcriptome-guided genetic analysis of correlated episodic memory
      phenotypes in Alzheimer's disease.
AB  - As the most common type of dementia, Alzheimer's disease (AD) is a
      neurodegenerative disorder initially manifested by impaired memory performances.
      While the diagnosis information indicates a dichotomous status of a patient,
      memory scores have the potential to capture the continuous nature of the disease
      progression and may provide more insights into the underlying mechanism. In this
      work, we performed a targeted genetic study of memory scores on an AD cohort to
      identify the associations between a set of genes highly expressed in the
      hippocampal region and seven cognitive scores related to episodic memory. Both
      main effects and interaction effects of the targeted genetic markers on these
      correlated memory scores were examined. In addition to well-known AD genetic
      markers APOE and TOMM40, our analysis identified a new risk gene NAV2 through the
      gene-level main effect analysis. NAV2 was found to be significantly and
      consistently associated with all seven episodic memory scores. Genetic
      interaction analysis also yielded a few promising hits warranting further
      investigation, especially for the RAVLT list B Score. 

PMID- 25859261
TI  - Metabolic surgery: present and future.

PMID- 25859260
TI  - Go with the flow-biology and genetics of the lactation cycle.
AB  - Lactation is a dynamic process, which evolved to meet dietary demands of growing
      offspring. At the same time, the mother's metabolism changes to meet the high
      requirements of nutrient supply to the offspring. Through strong artificial
      selection, the strain of milk production on dairy cows is often associated with
      impaired health and fertility. This led to the incorporation of functional traits
      into breeding aims to counteract this negative association. Potentially,
      distributing the total quantity of milk per lactation cycle more equally over
      time could reduce the peak of physiological strain and improve health and
      fertility. During lactation many factors affect the production of milk: food
      intake; digestion, absorption, and transportation of nutrients; blood glucose
      levels; activity of cells in the mammary gland, liver, and adipose tissue;
      synthesis of proteins and fat in the secretory cells; and the metabolic and
      regulatory pathways that provide fatty acids, amino acids, and carbohydrates.
      Whilst the endocrine regulation and physiology of the dynamic process of milk
      production seems to be understood, the genetics that underlie these dynamics are
      still to be uncovered. Modeling of longitudinal traits and estimating the change
      in additive genetic variation over time has shown that the genetic contribution
      to the expression of a trait depends on the considered time-point. Such time
      dependent studies could contribute to the discovery of missing heritability. Only
      very few studies have estimated exact gene and marker effects at different time
      points during lactation. The most prominent gene affecting milk yield and milk
      fat, DGAT1, exhibits its main effects after peak production, whilst the casein
      genes have larger effects in early lactation. Understanding the physiological
      dynamics and elucidating the time-dependent genetic effects behind dynamically
      expressed traits will contribute to selection decisions to further improve
      productive and healthy breeding populations. 

PMID- 25859262
TI  - The success of sleeve gastrectomy in the management of metabolic syndrome and
      obesity.
AB  - The rapid reversal of diabetes, hypertension, hyperlipidaemia and obesity by
      surgical means has challenged accepted doctrines regarding the management of
      metabolic syndrome. Sleeve gastrectomy, which developed initially as a
      preparatory procedure for biliopancreatic diversion with duodenal switch, has
      seen an exponential rise in popularity as an effective lone laparoscopic
      bariatric procedure. Superior excess weight loss, a low complication rate, and
      excellent food tolerance, combined with a short hospital stay, have made this the
      procedure of choice for patients and surgeons across the globe. High volume
      centres nurture the ongoing development of experienced and specialized teams,
      pathways and regimens. Optimum surgical outcomes allow minimization of metabolic
      syndrome, reducing cardiovascular and cerebrovascular risk. 

PMID- 25859263
TI  - Recent advances in bariatric/metabolic surgery: appraisal of clinical evidence.
AB  - Obesity and associated type 2 diabetes mellitus (T2DM) are becoming a serious
      medical issue worldwide. Bariatric surgery has been shown to be the most
      effective and durable therapy for the treatment of morbid obese patients.
      Increasing data indicates bariatric surgery as metabolic surgery is an effective
      and novel therapy for not well controlled obese T2DM patients. The review of
      recent developments in bariatric/metabolic surgery covers 4 major fields. 1)
      Improvement of safety: recent advances in laparoscopic/metabolic surgery has made
      this minimal invasive surgery more than ten times safer than a decade ago. The
      safety profile of laparoscopic/metabolic surgery is compatible with that of
      laparoscopic cholecystectomy now. 2) New bariatric/metabolic surgery:
      laparoscopic sleeve gastrectomy (LSG) is becoming the leading bariatric surgery
      because of its simplicity and efficacy. Other new procedures, such as gastric
      plication, banded plication, single anastomosis (mini) gastric bypass and Duodeno
      jejunal bypass with sleeve gastrectomy have all been accepted as treatment
      modalities for bariatric/metabolic surgery. 3) Mechanism of bariatric/metabolic
      surgery: Restriction is the most important mechanism for bariatric surgery.
      Weight regain after bariatric surgery is usually associated with loss of
      restriction. Recent studies demonstrated that gut hormone, microbiota and bile
      acid changes after bariatric surgery may play an important role in durable weight
      loss as well as in T2DM remission. However, weight loss is still the cornerstone
      of T2DM remission after metabolic surgery. 4) PATIENT SELECTION: patients who may
      benefit most from bariatric surgery was found to be patients with insulin
      resistance. For Asian T2DM patients, the indication of metabolic surgery has been
      set to those with not well controlled (HbA1c > 7.5%) disease and with their BMI >
      27.5 Kg/m(2). A novel diabetes surgical score, ABCD score, is a simple system for
      predicting the success of surgical therapy for T2DM. 

PMID- 25859264
TI  - Metabolic bariatric surgery and type 2 diabetes mellitus: an endocrinologist's
      perspective.
AB  - Traditional treatment of T2DM consisting of modification of diet, an exercise
      regimen, and pharmacotherapy has problems of poor lifestyle modifications and
      fail tend of treatment over time, now bariatric surgery is recommended for
      treatment of obese patients with T2DM because its great improvements on weight
      loss and metabolic. In this article, effects of bariatric surgery on diabetes and
      diabetes-related complications are reviewed. 

PMID- 25859265
TI  - Roux-en-Y gastric bypass for Chinese type 2 diabetes mellitus patients with a BMI
      < 28 kg/m(2): a multi-institutional study.
AB  - Roux-en-Y gastric bypass surgery (RYGB) has been demonstrated to be successful
      for treating type-II diabetes mellitus (T2DM) patients with a body mass index
      (BMI) <30 kg/m(2), but reports of RYGB for T2DM patients with a BMI <28 kg/m(2)
      are lacking. T2DM patients with a BMI <28 kg/m(2) were prospectively recruited to
      participate in this study in four hospitals. The endpoint was T2DM remission
      (defined by fasting blood glucose (FBG) level <110 mg/dL and hemoglobin (Hb)A1c
      level <6.0% at 12 months postoperatively). Predictors of remission were
      investigated by univariate and multivariate analyses. Eighty-six patients were
      assessed. Eighty-five patients underwent RYGB, with one conversion to open
      surgery. We compared the values of various variables before and after surgery.
      The mean BMI decreased from 24.68+/-2.12 to 21.72+/-2.43 kg/m(2) (P<0.001). Fifty
      eight (67.4%) patients were not treated by drugs or insulin after surgery, and 20
      patients (23.3%) had complete remission of T2DM at 12 months after surgery with
      an acceptable number of complications. The mean HbA1c level in the remission
      group was significantly lower than that in the non-remission group. Patients with
      a higher weight, lower HbA1c level, higher C-peptide level, and higher FBG level
      were more likely to have T2DM remission in multivariate analyses. In conclusion,
      RYGB was effective and safe for treating T2DM patients with a BMI <28 kg/m(2).
      Complete remission can be predicted by cases having a higher weight, lower HbA1c
      level, higher C-peptide level, and higher FBG level. 

PMID- 25859266
TI  - Bariatric surgery in old age: a comparative study of laparoscopic Roux-en-Y
      gastric bypass and sleeve gastrectomy in an Asia centre of excellence.
AB  - Bariatric surgery has been proved to be the safest and efficient procedure in
      treating morbid obese patients, but data is still lacking in the elderly
      population. The aim of our study was to compare the safety and efficacy of
      laparoscopic Roux-en-Y gastric bypass (LRYGB) and sleeve gastrectomy (LSG) in
      patients aged more than 55 years. We performed a retrospective review of a
      prospectively collected database. All patients with body mass index (BMI) ?32
      kg/m(2) and aged more than 55 years undergoing LRYGB or LSG in BMI Surgery
      Centre, E-Da Hospital between January 2008 and December 2011 with at least one
      year of follow up were included for the analysis. Demography, peri-operative
      data, weight loss and surgical complications were all recorded and analyzed. Mean
      age and BMI of these 68 patients (22 males and 46 female) were 58.8 years (55-79
      years) and 39.5 kg/m(2) (32.00-60.40 kg/m(2)). LRYGB was performed in 44 patients
      and LSG in 24 patients. The two groups were comparable in their preoperative BMI,
      American Society of Anaesthesia (ASA) score and gender distribution. LSG patients
      were significantly older than patients receiving LRYGB. The proportion of type 2
      diabetes preoperatively was significantly higher in LRYGB patients as compared to
      LSG patients (88.63% vs. 50%; P < 0.01). The prevalence of other co-morbidities
      was similar and comparable between the groups. Mean BMI in the LRYGB and LSG
      groups at the end of 1 year were 28.8 kg/m(2) and 28.2 kg/m(2), respectively, and
      there was no statistically significant difference in mean percentage of excess
      weight loss (%EWL) at 1 year. The percentage of resolution of diabetes was
      significantly higher in LRYGB (69.2%) as compared to LSG (33.3%). On the other
      hand, there was no statistical difference in the percentage of resolution of
      hypertension, hyperlipidemia and fatty liver hepatitis. The overall morbidity and
      re-operation rate was higher in LRYGB patients. In morbidly elderly patients,
      both surgeries achieved good weight loss and resolution of comorbidities. LRYGB
      is superior to LSG in terms of diabetes remission but carries higher complication
      rates even at high volume centres. 

PMID- 25859267
TI  - Maternal inheritance of severe hypertriglyceridemia impairs glucose metabolism in
      offspring.
AB  - Maternally inherited familial hypercholesterolemia (FH) impairs glucose
      metabolism and increases cardiovascular risks in the offspring to a greater
      degree than paternal inherited FH. However, it remains unknown whether
      hypertriglyceridemia affects glucose metabolism via inheritance. In this study,
      we sought to compare the impact of maternally and paternally inherited
      hypertriglyceridemia on glucose and lipid metabolism in mice. ApoCIII transgenic
      mice with severe hypertriglyceridemia were mated with non-transgenic control mice
      to obtain 4 types of offspring: maternal non-transgenic control and maternal
      transgenic offspring, and paternal control and paternal transgenic offspring.
      Plasma triglycerides (TG), total cholesterol (TC), fasting plasma glucose (FPG)
      and fasting insulin (FINS) were measured. ApoCIII overexpression caused severe
      hypertriglyceridemia, but the transgenic female mice had unaltered fertility with
      normal pregnancy and birth of pups. The 4 groups of offspring had similar birth
      weight and growth rate. The plasma TG of maternal and paternal transgenic
      offspring were nearly 40-fold higher than maternal and paternal control mice, but
      there was no difference in plasma TG between maternal and paternal transgenic
      offspring. Although the FPG of the 4 groups of animals had no difference, the
      maternal transgenic mice showed impaired glucose tolerance, increased FINS levels
      and higher homeostasis model assessment insulin resistance index (HOMA-IR) than
      the other 3 groups. In conclusion, maternally inherited hypertriglyceridemia in
      ApoCIII transgenic mice displayed impaired glucose tolerance, hyperinsulinemia
      and increased HOMA-R, while paternally inherited hypertriglyceridemia did not
      have such impacts. 

PMID- 25859268
TI  - Osthole inhibits proliferation of human breast cancer cells by inducing cell
      cycle arrest and apoptosis.
AB  - Recent studies have revealed that osthole, an active constituent isolated from
      the fruit of Cnidium monnieri (L.) Cusson, a traditional Chinese medicine,
      possesses anticancer activity. However, its effect on breast cancer cells so far
      has not been elucidated clearly. In the present study, we evaluated the effects
      of osthole on the proliferation, cell cycle and apoptosis of human breast cancer
      cells MDA-MB 435. We demonstrated that osthole is effective in inhibiting the
      proliferation of MDA-MB 435 cells, The mitochondrion-mediated apoptotic pathway
      was involved in apoptosis induced by osthole, as indicated by activation of
      caspase-9 and caspase-3 followed by PARP degradation. The mechanism underlying
      its effect on the induction of G1 phase arrest was due to the up-regulation of
      p53 and p21 and down-regulation of Cdk2 and cyclin D1 expression. Were observed
      taken together, these findings suggest that the anticancer efficacy of osthole is
      mediated via induction of cell cycle arrest and apoptosis in human breast cancer
      cells and osthole may be a potential chemotherapeutic agent against human breast
      cancer. 

PMID- 25859269
TI  - Quercetin attenuates the development of 7, 12-dimethyl benz (a) anthracene (DMBA)
      and croton oil-induced skin cancer in mice.
AB  - To evaluate the chemopreventive potential of quercetin in an experimental skin
      carcinogenesis mouse model. Skin tumor was induced by topical application of 7,
      12-dimethyl Benz (a) anthracene (DMBA) and Croton oil in Swiss albino mouse.
      Quercetin was orally administered at a concentration of 200 mg/kg and 400 mg/kg
      body weight daily for 16 weeks in mouse to evaluate chemopreventive potential.
      Skin cancer was assessed by histopathological analysis. We found that quercetin
      reduced the tumor size and the cumulative number of papillomas. The mean latent
      period was significantly increased as compared to carcinogen treated controls.
      Quercetin significantly decreased the serum levels of glutamate oxalate
      transaminase, glutamate pyruvate transaminase, alkaline phosphatase and
      bilirubin. It significantly increased the levels of glutathione, superoxide
      dismutase and catalase. The elevated level of lipid peroxides in the control
      group was significantly inhibited by quercetin. Futhermore, DNA damage was
      significantly decreased in quercetin treated mice as compared to DMBA and croton
      oil treated mice. The results suggest that quercetin exerts chemopreventive
      effect on DMBA and croton oil induced skin cancer in mice by increasing
      antioxidant activities. 

PMID- 25859270
TI  - Evaluation of metal nanoparticles for drug delivery systems.
AB  - Diminazene aceturate is a trypanocide with unwanted toxicity and limited
      efficacy. It was reasoned that conjugating diminazene aceturate to functionalized
      nanoparticle would lower untoward toxicity while improving selectivity and
      therapeutic efficacy. Silver and gold nanoparticles were evaluated for their
      capacities to serve as carriers for diminazene aceturate. The silver and gold
      nanoparticles were synthesized, functionalized and coupled to diminazene
      aceturate following established protocols. The nanoparticle conjugates were
      characterized. The free diminazene aceturate and drug conjugated nanoparticles
      were subsequently evaluated for cytotoxicity in vitro. The characterizations by
      transmission electron microscopy or UV/Vis spectroscopy revealed that conjugation
      of diminazene aceturate to silver or gold nanoparticles was successful.
      Evaluation for cytotoxic actions in vitro demonstrated no significance difference
      between free diminazene aceturate and the conjugates. Our data suggest that
      surface modified metal nanoparticles could be optimized for drug delivery
      systems. 

PMID- 25859271
TI  - In silico modification of oseltamivir as neuraminidase inhibitor of influenza A
      virus subtype H1N1.
AB  - This research focused on the modification of the functional groups of oseltamivir
      as neuraminidase inhibitor against influenza A virus subtype H1N1. Interactions
      of three of the best ligands were evaluated in the hydrated state using molecular
      dynamics simulation at two different temperatures. The docking result showed that
      AD3BF2D ligand (N-[(1S,6R)-5-amino-5-{[(2R,3S,4S)-3,4-dihydroxy-4-(hydroxymethyl)
      tetrahydrofuran-2-yl]oxy}-4-formylcyclohex-3-en-1-yl]acetamide-3-(1-ethylpropoxy)
      1-cyclohexene-1-carboxylate) had better binding energy values than standard
      oseltamivir. AD3BF2D had several interactions, including hydrogen bonds, with the
      residues in the catalytic site of neuraminidase as identified by molecular
      dynamics simulation. The results showed that AD3BF2D ligand can be used as a good
      candidate for neuraminidase inhibitor to cope with influenza A virus subtype
      H1N1. 

PMID- 25859273
TI  - Quantitative variation of bioactive phyto compounds in ethyl acetate and methanol
      extracts of Pergularia daemia (Forsk.) Chiov.

PMID- 25859272
TI  - Efficacy of biofeedback therapy via a mini wireless device on sleep bruxism
      contrasted with occlusal splint: a pilot study.
AB  - The putative causes of bruxism are multifactorial and there are no definite
      measures for bruxism management. The aim of this study was to evaluate the
      efficacy of biofeedback therapy on sleep bruxism, compared with occlusal splint.
      Twenty-four volunteers with sleep bruxism were divided into two groups: the GTB
      group that were treated with biofeedback therapy (n  = 12) and the GTO group that
      were treated with occlusal splint (n  = 12). A mini pressure sensor integrated
      with a monitoring circuit by use of a maxillary biofeedback splint was
      fabricated. To foster the relaxation of the masticatory muscles and the nervous
      system, the wireless device received signals from bruxism events and vibrations
      alerted the bruxer when the threshold was exceeded. Total episodes and average
      duration of bruxism events during 8 hours of sleep were analyzed with the
      monitoring program (TRMY1.0). After 6 and 12 weeks, the episodes (P  =  0.001)
      and duration (P < 0.05) in the GTB group declined dramatically. In contrast,
      there were no significant differences in the GTO group after the treatment (P >
      0.05). Furthermore, the episodes had significant differences between the GTB
      group and the GTO group after the same period of treatment (P  =  0.000). The
      results suggest that biofeedback therapy may be an effective and convenient
      measure for mild bruxers, when compared with occlusal splint therapy. The mini
      wireless biofeedback method may be of value for the diagnosis and management of
      bruxism in the future. 

PMID- 25859274
TI  - Central obesity and other factors associated with uncontrolled asthma in women.
AB  - BACKGROUND: Asthma remains an uncontrolled disease. The Comorbidities,
      particularly obesity, and several other factors have been identified as being
      individually associated with asthma control, and these factors vary among
      different countries and between sexes. Studies have suggested that the harmful
      effects of these factors are greatest among women. The aim of the present study
      was to identify associated factors with uncontrolled asthma in women at the
      outpatient clinic of a Federal University Hospital in Rio de Janeiro, Brazil.
      METHODS: Cross-sectional study with asthmatic women, older than 18 years old. All
      subjects were included according to stringent criteria. The study used a
      structured questionnaire with data about demographic variables, education level,
      comorbid conditions, and disease history. Anthropometric and spirometric
      measurements were obtained. Asthma control was assessed by three different tools:
      the Asthma Control Test (ACT), the Asthma Control Questionnaire (ACQ) and the
      Global Initiative for Asthma (GINA) criteria. RESULTS: A total of 124 women were
      included, and 57%, 38% and 21% were totally controlled according to ACT, ACQ and
      GINA criteria, respectively. A total of 31.5% were obese. According to the CI
      (Conicity Index) and WC (waist circumference) respectively, 84% and 68% were
      centrally obese. There was no association between asthma control and age,
      education, duration of the disease or BMI (Body Mass Index) in the three models,
      but there was a significant association between central obesity and asthma
      control with the ACQ and GINA assessment tools, controlling for explanatory
      variables such as GERD (gastroesophageal reflux disease). Pre-bronchodilator
      percent predicted forced expiratory volume in one second (FEV1) and forced vital
      capacity (FVC) were significantly associated with age and FVC was also associated
      with central obesity. CONCLUSIONS: Asthma remains uncontrolled in women despite
      treatment, and central obesity seems to have a negative influence on the control
      of the disease. We believe that women should be studied as a separate group and
      suggest prospective studies with assessment of fat distribution and biomarkers,
      controlling for possible comorbidities associated with asthma control.

PMID- 25859276
TI  - On the family-free DCJ distance and similarity.
AB  - Structural variation in genomes can be revealed by many (dis)similarity measures.
      Rearrangement operations, such as the so called double-cut-and-join (DCJ), are
      large-scale mutations that can create complex changes and produce such variations
      in genomes. A basic task in comparative genomics is to find the rearrangement
      distance between two given genomes, i.e., the minimum number of rearragement
      operations that transform one given genome into another one. In a family-based
      setting, genes are grouped into gene families and efficient algorithms have
      already been presented to compute the DCJ distance between two given genomes. In
      this work we propose the problem of computing the DCJ distance of two given
      genomes without prior gene family assignment, directly using the pairwise
      similarities between genes. We prove that this new family-free DCJ distance
      problem is APX-hard and provide an integer linear program to its solution. We
      also study a family-free DCJ similarity and prove that its computation is NP
      hard. 

PMID- 25859275
TI  - Revisiting loxapine: a systematic review.
AB  - Loxapine is an antipsychotic used in psychiatry for over 40 years with a well
      established profile. Loxapine is a dibenzoxazepine tricyclic antipsychotic agent,
      available for oral, intramuscular and inhalatory administration. In the light of
      the recent approval by the regulatory agencies of inhaled loxapine for use in the
      acute treatment of mild-to-moderate agitation in adults affected with
      schizophrenia or bipolar disorder, this article aims to critically review the
      available literature on loxapine, irrespective of its formulation. This review
      examines the efficacy and tolerability of the various formulations of loxapine in
      the treatment of agitation and aggression in patients affected with
      schizophrenia, bipolar disorder and other psychiatric conditions. A comprehensive
      and systematic literature search of PubMed/MEDLINE was conducted, and relevant
      pharmacodynamic and pharmacokinetic data was included. The findings from the
      literature were critically reviewed and synthesized. The available data suggests
      that the antipsychotic efficacy of loxapine is similar to the efficacy of other
      typical or atypical antipsychotics, with an adverse effects profile comparable to
      that of the typical antipsychotics at high doses for chronic treatment. As an
      acute treatment in agitation associated with schizophrenia or bipolar disorder,
      inhaled loxapine was developed as an innovative and rapid option which appears to
      be efficacious and tolerable. 

PMID- 25859277
TI  - NaCl pretreatment attenuates H.pylori-induced DNA damage and exacerbates
      proliferation of gastric epithelial cells (GES-1).
AB  - BACKGROUND: Both H. pylori infection and high salt (NaCl) diet are risks of
      gastric cancer, however, the interaction pattern of the two is not very clear.
      Our objective was to investigate the effects of NaCl-pretreated H. pylori on DNA
      damage and proliferation of gastric epithelial cell (GES-1). METHODS: GES-1 cells
      were co-cultured with H.pylori or NaCl-pretreated H. pylori (with 30% NaCl) for
      24 h. The morphological changes of all cells were observed by inverted phase
      contrast microscopy and transmission electron microscopy. Oxidative DNA damage
      was examined by immunofluorescence. Alterations in mitochondrial membrane
      potential and apoptosis rate were detected by flow cytometry and western blot,
      and expression of Ki-67, PCNA and P21 were evaluated using the immunocytochemical
      staining. RESULTS: GES-1 cells co-cultured with NaCl-pretreated H.pylori
      exhibited morphological changes and oxidative DNA damage. Although no significant
      disruption of the mitochondrial membrane potential (DeltaPsim) and apoptotic rate
      were observed compared with control groups, there were significant decreased in
      Bax and Caspase3 proteins and increased in Bcl-2 protein in GES-1 cells infected
      with H. pylori (30) when compared with GES-1 cells cultured with H. pylori. In
      addition, we found a proliferative effect on GES-1 cells with an increased
      expression of Ki-67 and PCNA as well as a decreased p21 expression, through which
      the cells may acquire the potential for malignant transformation. CONCLUSION:
      NaCl-pretreated H. pylori possessed the ability to cause cell injury and promote
      proliferation in gastric epithelial cells.

PMID- 25859278
TI  - Associations of betatrophin levels with irisin in Chinese women with normal
      glucose tolerance.
AB  - BACKGROUND: Betatrophin may increase islet beta cell proliferation in insulin
      resistance and irisin may improve glucose tolerance in mice. To examine the
      relationship between betatrophin and irisin, we investigated it in middle-aged
      Chinese subjects with normal glucose tolerance (NGT) and type 2 diabetes mellitus
      (T2DM). METHODS: A total of 460 permanent residents of Fengxian District, aged 40
      60 years and without T2DM, were enrolled. Anthropometric parameters, oral glucose
      tolerance test (OGTT) results, glycosylated haemoglobin levels, blood lipid
      levels, insulin sensitivity (homeostasis model assessment of insulin resistance,
      HOMA-IR), beta cell function (homeostasis model assessment-beta, HOMA-beta),
      estimated glomerular filtration rate (eGFR) and body fat composition were
      determined. Matched for age, gender and body mass index (BMI, 18-28 kg/m2), newly
      diagnosed T2DM (n = 50, male/female = 23/27) and NGT (n = 50, male/female =
      21/29) subjects were selected based on the results of an OGTT. Serum betatrophin
      and irisin levels were determined by enzyme linked immune sorbent assay (ELISA).
      RESULTS: Males had higher levels of betatrophin compared with females in both the
      NGT and T2DM groups. Compared with NGT subjects, the level of betatrophin in the
      T2DM group was higher, and males in the T2DM group had higher betatrophin levels
      than males in the NGT group, but there was no significant difference in
      betatrophin levels in females between the T2DM and NGT groups. Spearman's
      correlation analysis revealed that serum betatrophin levels in females with NGT
      were positively correlated with irisin and negatively correlated with FINS
      (fasting insulin) levels ( p < 0.05), but no correlation was found between
      betatrophin and irisin levels in males with NGT or in males or females with T2DM.
      In females with T2DM, circulating betatrophin levels were positively correlated
      with weight, BMI and hip circumference (p < 0.05) but negatively correlated with
      FPG (fasting plasma glucose) and HOMA-IR (p < 0.05). CONCLUSIONS: Gender
      differences in the relationship between betatrophin and irisin indicate that
      there might be cytokine-mediated crosstalk among the liver, adipose tissue and
      skeletal muscle.

PMID- 25859279
TI  - Evaluation of epicardial adipose tissue in familial partial lipodystrophy.
AB  - BACKGROUND: Dunnigan type Familial Partial Lipodystrophy (FPLD) is characterized
      by loss of subcutaneous fat from the limbs and excessive accumulation on the
      visceral adipose tissue (VAT). Affected individuals have insulin resistance (IR),
      diabetes, dyslipidemia and early cardiovascular (CV) events, due to their
      imbalanced distribution of total body fat (TBF). Epicardial adipose tissue (EAT)
      is correlated with VAT. Hence, EAT could be a new index of cardiac and visceral
      adiposity with great potential as a marker of CV risk in FPLD. OBJECTIVE: Compare
      EAT in FPLD patients versus healthy controls. Moreover, we aimed to verify if EFT
      is related to anthropometrical (ATPM) and Dual-Energy X-ray Absorptiometry (DEXA)
      measures, as well as laboratory blood findings. We postulated that FPLD patients
      have enlarged EAT. METHODS: This is an observational, cross-sectional study. Six
      patients with a confirmed mutation in the LMNA gene for FPLD were enrolled in the
      study. Six sex, age and BMI-matched healthy controls were also selected. EFT was
      measured by transthoracic echocardiography (ECHO). All participants had body fat
      distribution evaluated by ATPM and by DEXA measures. Fasting blood samples were
      obtained for biochemical profiles and also for leptin measurements. RESULTS:
      Median EFT was significantly higher in the FPLD group than in matched controls
      (6.0 +/- 3.6 mm vs. 0.0 +/- 2.04 mm; p = 0.0306). Additionally, FPLD patients had
      lower leptin values. There was no significant correlation between EAT and ATPM
      and DEXA measurements, nor laboratory findings. CONCLUSIONS: This study
      demonstrates, for the first time, that EAT measured by ECHO is increased in FPLD
      patients, compared to healthy controls. However, it failed to prove a significant
      relation neither between EAT and DEXA, ATPM or laboratory variables analyzed.

PMID- 25859281
TI  - Health literacy and blood glucose among Guyanese emergency department patients
      without diagnosed diabetes: a cross-sectional study.
AB  - BACKGROUND: Low health literacy is associated with worse glycemic control among
      patients with diabetes; the relationship between health literacy and blood
      glucose among patients without diagnosed diabetes, particularly in resource
      limited settings, is not known. Because emergency department patients are at risk
      for both low health literacy and undiagnosed diabetes, we examined their
      relationships among emergency department patients at the Georgetown Public
      Hospital Corporation in Guyana. METHODS: We conducted a cross-sectional study
      across random time blocks from May to August 2012 among Guyanese emergency
      department patients without a diagnosis of diabetes. Health literacy was assessed
      by the Single Item Literacy Screener (SILS, range 1-5); low health literacy was
      defined as SILS >= 3. We examined the relationships among health literacy, random
      blood glucose (RBG), and point-of-care glycated hemoglobin (HbA1c). RESULTS: Of
      the 228 enrolled patients, 125 (54%) were female, median age was 43 years
      (interquartile range 38 to 53), mean body mass index (BMI) was 25.6 kg/m(2)
      (standard deviation 6.8 kg/m(2)), and 103 (45.2%) had low health literacy. The
      receiver operating characteristic area under the curve for RBG to detect elevated
      HbA1c (>=48mmol/mol) was 0.94 (95% CI: 0.91-0.97). After adjustment for age, sex,
      BMI, ethnicity, and education, the odds of having HbA1c >= 48 mmol/mol,
      consistent with undiagnosed diabetes, rose with decreasing health literacy (OR
      2.2, 95% CI 1.2-3.8, p = 0.007, per point decrease in literacy). CONCLUSION: This
      pilot study of Guyanese emergency department patients without diagnosed diabetes
      found that low health literacy was common and was associated with higher HbA1c
      and random blood glucose.

PMID- 25859280
TI  - IRS-1 gene polymorphism and DNA damage in pregnant women with diabetes or mild
      gestational hyperglycemia.
AB  - BACKGROUND: Pregnant women with mild gestational hyperglycemia present a high
      risk for hypertension and obesity, and appear to reproduce the model of metabolic
      syndrome in pregnancy, including hyperinsulinemia and insulin resistance.
      Diabetic patients have a higher frequency of the IRS-1 Gly972Arg variant and this
      polymorphism is directly related to insulin resistance and subsequent
      hyperglycemia. In diabetes, hyperglycemia and other associated factors generate
      reactive oxygen species that increase DNA damage. The aims of this study were to
      evaluate the presence of the IRS-1 Arg972 polymorphism in pregnant women with
      diabetes or mild gestational hyperglycemia, and in their newborns. Additionally,
      we evaluated the level of primary DNA damage in lymphocytes of Brazilian pregnant
      women and the relationship between the amount of genetic damage and presence of
      the polymorphism. METHODS: A based on the oral glucose tolerance test (OGTT)
      results and on glycemic profiles (GP), as follows: non-diabetic group, mild
      gestational hyperglycemia (MGH) and diabetic group. Eighty-five newborns were
      included in the study. Maternal peripheral blood samples and umbilical cord blood
      samples (5-10 mL) were collected for genotyping by PCR-RFLP and for comet assays.
      RESULTS: The prevalence of genotype Gly/Arg in pregnant women groups was not
      statistically significant. In newborns, the frequency of Gly/Arg was
      significantly higher in the MGH and diabetic groups than in the non-diabetic
      group. Taken together, groups IIA and IIB (IIA + IIB; diabetes) presented lower
      amounts of DNA damage than the non-diabetic group (p = 0.064). No significant
      association was detected between genetic damage and the presence of the Arg972
      genotype in pregnant women. CONCLUSION: The polymorphism was more prevalent in
      newborns of diabetic and MGH women. We believe that it is necessary to increase
      the number of subjects to be examined in order to better determine the biological
      role of the Arg972 polymorphism in these patients. Despite being classified as
      low-risk, pregnant women with mild gestational hyperglycemia characterize a
      population of maternal and perinatal adverse outcomes, and that, together with
      their newborns, require better monitoring by professionals and health services.

PMID- 25859282
TI  - Follow-up plasma apolipoprotein E levels in the Australian Imaging, Biomarkers
      and Lifestyle Flagship Study of Ageing (AIBL) cohort.
AB  - INTRODUCTION: Alzheimer's disease (AD) is a growing socioeconomic problem
      worldwide. Early diagnosis and prevention of this devastating disease have become
      a research priority. Consequently, the identification of clinically significant
      and sensitive blood biomarkers for its early detection is very important.
      Apolipoprotein E (APOE) is a well-known and established genetic risk factor for
      late-onset AD; however, the impact of the protein level on AD risk is unclear. We
      assessed the utility of plasma ApoE protein as a potential biomarker of AD in the
      large, well-characterised Australian Imaging, Biomarkers and Lifestyle Study of
      Ageing (AIBL) cohort. METHODS: Total plasma ApoE levels were measured at 18-month
      follow-up using a commercial bead-based enzyme-linked immunosorbent assay: the
      Luminex xMAP human apolipoprotein kit. ApoE levels were then analysed between
      clinical classifications (healthy controls, mild cognitive impairment (MCI) and
      AD) and correlated with the data available from the AIBL cohort, including but
      not limited to APOE genotype and cerebral amyloid burden. RESULTS: A significant
      decrease in ApoE levels was found in the AD group compared with the healthy
      controls. These results validate previously published ApoE protein levels at
      baseline obtained using different methodology. ApoE protein levels were also
      significantly affected, depending on APOE genotypes, with epsilon2/epsilon2
      having the highest protein levels and epsilon4/epsilon4 having the lowest. Plasma
      ApoE levels were significantly negatively correlated with cerebral amyloid burden
      as measured by neuroimaging. CONCLUSIONS: ApoE is decreased in individuals with
      AD compared with healthy controls at 18-month follow-up, and this trend is
      consistent with our results published at baseline. The influence of APOE genotype
      and sex on the protein levels are also explored. It is clear that ApoE is a
      strong player in the aetiology of this disease at both the protein and genetic
      levels.

PMID- 25859284
TI  - LINE-1 hypomethylation is neither present in rectal aberrant crypt foci nor
      associated with field defect in sporadic colorectal neoplasia.
AB  - BACKGROUND: Aberrant crypt foci (ACF) are considered the first identifiable
      preneoplastic lesion in colorectal cancer (CRC), and have been proposed as a
      potential biomarker for CRC risk. Global DNA hypomethylation is an early event in
      colorectal carcinogenesis, and long interspersed nuclear element-1 (LINE-1)
      methylation status is a well-known surrogate marker for genome-wide DNA
      methylation levels. Despite the gradual increase in DNA hypomethylation in the
      adenoma-carcinoma sequence, LINE-1 methylation in ACF has never been studied.
      Moreover, recent studies have reported a field defect for LINE-1 hypomethylation,
      suggesting that LINE-1 methylation status in normal mucosa could be used to
      stratify CRC risk and tailor preventive strategies. Thus, we assessed LINE-1
      status by pyrosequencing in rectal ACF and paired normal colorectal mucosa from
      individuals with sporadic colon cancer (CC) (n = 35) or adenoma (n = 42), and
      from healthy controls (n = 70). FINDINGS: Compared with normal mucosa, LINE-1 in
      ACF were hypermethylated across all groups (P < 0.0001). Furthermore, LINE-1
      methylation status in normal colorectal mucosa was independent of the presence of
      adenoma or CC (P = 0.1072), and did not differ depending on the distance to the
      adenoma or CC. Interestingly, when we compared the LINE-1 methylation status in
      normal mucosa from different segments of the colorectum, we found higher
      hypomethylation in the rectum compared with the descending colon (P < 0.0001).
      CONCLUSIONS: Overall, our results suggest that global hypomethylation is not
      present in rectal ACF and argues against the existence of LINE-1 methylation
      field defect in sporadic colon cancer.

PMID- 25859283
TI  - Quantitative methodology is critical for assessing DNA methylation and impacts on
      correlation with patient outcome.
AB  - BACKGROUND: DNA hypermethylation is reported as a frequent event and prognostic
      marker in head and neck squamous cell carcinomas (HNSCC). Methylation has been
      commonly assessed with non-quantitative methodologies, such as methylation
      specific PCR (MSP). We investigated previously reported hypermethylated genes
      with quantitative methodology in oral tongue squamous cell carcinomas (OTSCC).
      RESULTS: The methylation status of 12 genes in 115 OTSCC samples was assessed by
      one or more of three quantitative analyses: methylation sensitive high resolution
      melting (MS-HRM), sensitive-melting analysis after real time-methylation specific
      PCR (SMART-MSP), and bisulfite pyrosequencing. In contrast to much of the
      literature, either no or infrequent locus-specific methylation was identified by
      MS-HRM for DAPK1, RASSF1A, MGMT, MLH1, APC, CDH1, CDH13, BRCA1, ERCC1, and ATM.
      The most frequently methylated loci were RUNX3 (18/108 methylated) and ABO
      (22/107 methylated). Interrogation of the Cancer Genome Atlas (TCGA) HNSCC cohort
      confirmed the frequency of significant methylation for the loci investigated.
      Heterogeneous methylation of RUNX3 (18/108) and ABO (22/107) detected by MS-HRM,
      conferred significantly worse survival (P = 0.01, and P = 0.03). However,
      following quantification of methylation levels using pyrosequencing, only four
      tumors had significant quantities (>15%) of RUNX3 methylation which correlated
      with a worse patient outcome (P <0.001), while the prognostic significance of ABO
      hypermethylation was lost. RUNX3 methylation was not prognostic for the TCGA
      cohort (P = 0.76). CONCLUSIONS: We demonstrated the critical need for
      quantification of methylation levels and its impact on correlative analyses. In
      OTSCC, we found little evidence of significant or frequent hypermethylation of
      many loci reported to be commonly methylated. It is likely that previous reports
      have overestimated the frequency of significant methylation events as a
      consequence of the use of non-quantitative methodology.

PMID- 25859285
TI  - Restitution of gene expression and histone acetylation signatures altered by
      hepatitis B virus through antiviral microRNA-like molecules in nontransformed
      murine hepatocytes.
AB  - BACKGROUND: Virus-host interactions result in altered gene expression profiles in
      host cell nuclei and enable virus particle production, thus obligatorily
      involving changes in their epigenomes. Neither such epigenome changes nor their
      response to antiviral treatment have been extensively studied to date, although
      viral infections are known to contribute to the long-term development of severe
      secondary diseases, for example, hepatocellular carcinoma. This may be causally
      linked to virus-induced persistent plastic chromatin deformations. RESULTS: We
      studied whether impaired hepatitis B virus (HBV) replication can lead to the
      restitution of epigenome signatures hypothesizing that hepatocytes alternatively
      could adopt a 'memory' state of the infection; that is, the chromatin could
      persist in a HBV-induced configuration potentially inheritable between dividing
      hepatocytes. We therefore determined epigenomic signatures and gene expression
      changes altered by HBV and the effects of suppressed HBV replication in
      nontransformed hepatocytes of newborn mice. Further we investigated differential
      histone acetyltransferase and histone deacetylase activities in HBV-negative and
      HBVpositive hepatocytes, as well as the effects of HBV suppression on gene
      expression and the chromatin landscape. We show that the expression of several
      genes and the chromatin landscape become altered upon HBV infection, including
      global hypoacetylation of H2A.Z and H3K9. Reporter assays monitoring the
      activities of histone acetyltransferases or histone deacetylases, respectively,
      suggest that hypoacetylation most probably depends on elevated sirtuin
      deacetylase activity, but not on class I/II histone deacetylases. Using
      Micrococcus nuclease to study the chromatin accessibility in met murine-D3 and
      hepatitis B virus met murine hepatocytes, we demonstrate that the observed
      differences in H2A.Z/H3K9 acetylation lead to global chromatin structure changes.
      At all selected sites examined by chromatin immunoprecipitation and quantitative
      real-time PCR, these effects can be partly restituted via the nucleoside analog
      reverse transcriptase inhibitor 3TC or using anti-HBV microRNA-like molecules.
      CONCLUSIONS: Increased sirtuin activity might lead to global histone
      hypoacetylation signatures, which could contribute to the HBV-induced
      pathomechanism in nontransformed hepatocytes. Using several techniques to
      suppress HBV replication, we observed restituted gene expression and chromatin
      signature patterns reminiscent of noninfected hepatocytes. Importantly, ectopic
      expression of antiviral short-hairpin RNA, but not microRNA-like molecules,
      provoked intolerable off-target effects on the gene expression level.

PMID- 25859286
TI  - Leucine alters hepatic glucose/lipid homeostasis via the myostatin-AMP-activated
      protein kinase pathway - potential implications for nonalcoholic fatty liver
      disease.
AB  - BACKGROUND: Elevated plasma levels of the branched-chain amino acid (BCAA)
      leucine are associated with obesity and insulin resistance (IR), and thus the
      propensity for type 2 diabetes mellitus development. However, other clinical
      studies suggest the contradictory view that leucine may in fact offer a degree of
      protection against metabolic syndrome. Aiming to resolve this apparent paradox,
      we assessed the effect of leucine supplementation on the metabolism of human
      hepatic HepG2 cells. RESULTS: We demonstrate that pathophysiological leucine
      appears to be antagonistic to insulin, promotes glucose uptake (and not glycogen
      synthesis), but results in hepatic cell triglyceride (TG) accumulation. Further,
      we provide evidence that myostatin (MSTN) regulation of AMP-activated protein
      kinase (AMPK) is a key pathway in the metabolic effects elicited by excess
      leucine. Finally, we report associated changes in miRNA expression (some species
      previously linked to metabolic disease etiology), suggesting that epigenetic
      processes may contribute to these effects. CONCLUSIONS: Collectively, our
      observations suggest leucine may be both 'friend' and 'foe' in the context of
      metabolic syndrome, promoting glucose sequestration and driving lipid
      accumulation in liver cells. These observations provide insight into the clinical
      consequences of excess plasma leucine, particularly for hyperglycemia, IR and
      nonalcoholic fatty liver disease (NAFLD).

PMID- 25859287
TI  - Methylation array data can simultaneously identify individuals and convey
      protected health information: an unrecognized ethical concern.
AB  - BACKGROUND: Genome-wide methylation arrays are increasingly used tools in studies
      of complex medical disorders. Because of their expense and potential utility to
      the scientific community, current federal policy dictates that data from these
      arrays, like those from genome-wide genotyping arrays, be deposited in publicly
      available databases. Unlike the genotyping information, access to the expression
      data is not restricted. An underlying supposition in the current nonrestricted
      access to methylation data is the belief that protected health and personal
      identifying information cannot be simultaneously extracted from these arrays.
      RESULTS: In this communication, we analyze methylation data from the Illumina
      HumanMethylation450 array and show that genotype at 1,069 highly informative
      loci, and both alcohol and smoking consumption information, can be derived from
      the array data. CONCLUSIONS: We conclude that both potentially personally
      identifying information and substance-use histories can be simultaneously derived
      from methylation array data. Because access to genetic information about a
      database subject or one of their relatives is critical to the de-identification
      process, this risk of de-identification is limited at the current time. We
      propose that access to genome-wide methylation data be restricted to
      institutionally approved investigators who accede to data use agreements
      prohibiting re-identification.

PMID- 25859288
TI  - Genome-wide methylation profiling of the different stages of hepatitis B virus
      related hepatocellular carcinoma development in plasma cell-free DNA reveals
      potential biomarkers for early detection and high-risk monitoring of
      hepatocellular carcinoma.
AB  - BACKGROUND: An important model of hepatocellular carcinoma (HCC) that has been
      described in southeast Asia includes the transition from chronic hepatitis B
      infection (CHB) to liver cirrhosis (LC) and, finally, to HCC. The genome-wide
      methylation profiling of plasma cell-free DNA (cfDNA) has not previously been
      used to assess HCC development. Using MethylCap-seq, we analyzed the genome-wide
      cfDNA methylation profiles by separately pooling healthy control (HC), CHB, LC
      and HCC samples and independently validating the library data for the tissue DNA
      and cfDNA by MSP, qMSP and Multiplex-BSP-seq. RESULTS: The dynamic features of
      cfDNA methylation coincided with the natural course of HCC development. Data
      mining revealed the presence of 240, 272 and 286 differentially methylated genes
      (DMGs) corresponding to the early, middle and late stages of HCC progression,
      respectively. The validation of the DNA and cfDNA results in independent tissues
      identified three DMGs, including ZNF300, SLC22A20 and SHISA7, with the potential
      for distinguishing between CHB and LC as well as between LC and HCC. The area
      under the curve (AUC) ranged from 0.65 to 0.80, and the odds ratio (OR) values
      ranged from 5.18 to 14.2. CONCLUSIONS: Our data revealed highly dynamic cfDNA
      methylation profiles in support of HBV-related HCC development. We have
      identified a panel of DMGs that are predictive for the early, middle and late
      stages of HCC development, and these are potential markers for the early
      detection of HCC as well as the screening of high-risk populations.

PMID- 25859289
TI  - Differential DNA methylation of genes involved in fibrosis progression in non
      alcoholic fatty liver disease and alcoholic liver disease.
AB  - BACKGROUND: Chronic liver injury can lead to the development of liver fibrosis
      and cirrhosis but only in a minority of patients. Currently, it is not clear
      which factors determine progression to fibrosis. We investigated whether
      DNA?methylation profile as determined by pyrosequencing can distinguish patients
      with mild from those with advanced/severe fibrosis in non-alcoholic liver disease
      (NAFLD) and alcoholic liver disease (ALD). To this end, paraffin-embedded liver
      biopsies were collected from patients with biopsy-proven NAFLD or ALD, as well as
      paraffin-embedded normal liver resections, genomic DNA isolated, bisulfite
      converted and pyrosequencing assays used to quantify DNA methylation at specific
      CpGs within PPARalpha, PPARalpha, TGFbeta1, Collagen 1A1 and PDGFalpha genes.
      Furthermore, we assessed the impact of age, gender and anatomical location within
      the liver on patterns of DNA methylation in the same panel of genes. RESULTS: DNA
      methylation at specific CpGs within genes known to affect fibrogenesis
      distinguishes between patients with mild from those with severe fibrosis in both
      NAFLD and ALD, although same CpGs are not equally represented in both etiologies.
      In normal liver, age, gender or anatomical location had no significant impact on
      DNA methylation patterns in the liver. CONCLUSIONS: DNA methylation status at
      specific CpGs may be useful as part of a wider set of patient data for predicting
      progression to liver fibrosis.

PMID- 25859290
TI  - Differences in DNA methylation profile of Th1 and Th2 cytokine genes are
      associated with tolerance acquisition in children with IgE-mediated cow's milk
      allergy.
AB  - BACKGROUND: Epigenetic changes in DNA methylation could regulate the expression
      of several allergy-related genes. We investigated whether tolerance acquisition
      in children with immunoglobulin E (IgE)-mediated cow's milk allergy (CMA) is
      characterized by a specific DNA methylation profile of Th2 (IL-4, IL-5) and Th1
      (IL-10, IFN-gamma)-associated cytokine genes. RESULTS: DNA methylation of CpGs in
      the promoting regions of genes from peripheral blood mononuclear cells and serum
      level of IL-4, IL-5, IL-10 and INF-gamma were assessed in children with active
      IgE-mediated CMA (group 1), in children who acquired tolerance to cow's milk
      proteins (group 2) and in healthy children (group 3). Forty children (24 boys,
      aged 3 to 18 months) were enrolled: 10 in group 1, 20 in group 2, and 10 in the
      control group. The DNA methylation profiles clearly separated active CMA patients
      from healthy controls. We observed an opposite pattern comparing subjects with
      active IgE-mediated CMA with healthy controls and group 2 children who outgrew
      CMA. The IL-4 and IL-5 DNA methylation was significantly lower, and IL-10 and INF
      gamma DNA methylation was higher in active IgE-mediated CMA patients. Gene
      promoter DNA methylation rates of all cytokines and respective serum levels were
      strongly correlated. Formula selection significantly influenced cytokine DNA
      methylation profiles in group 2. CONCLUSIONS: Tolerance acquisition in children
      with IgE-mediated CMA is characterized by a distinct Th1 and Th2 cytokine gene
      DNA methylation pattern. These results suggest that DNA methylation may be a
      target for CMA prevention and treatment.

PMID- 25859292
TI  - The rice ALS3 encoding a novel pentatricopeptide repeat protein is required for
      chloroplast development and seedling growth.
AB  - BACKGROUND: Pentatricopeptide repeat (PPR) proteins play essential roles in
      modulating the expression of organelle genes and have expanded greatly in higher
      plants. However, molecular mechanisms of most rice PPR genes remain unclear.
      RESULTS: In this study, a new rice PPR mutant, asl3 (albino seedling lethality3)
      exhibits an albino lethal phenotype at the seedling stage. This albino phenotype
      was associated with altered photosynthetic-pigment and chloroplast development.
      Map-based cloning showed that ASL3 encodes a novel rice PPR protein with 10
      tandem PPR motifs, which localizes to the chloroplast. ASL3 showed tissue
      specific expression, as it was highly expressed in the chlorenchyma, but
      expressed at much lower levels in roots and panicles. RNAi of ASL3 confirmed that
      ASL3 plays an essential role in the early development and chloroplast development
      in rice. Moreover, expression analysis revealed that the asl3 mutation severely
      affected the transcriptional levels of important genes associated with plastid
      translation machinery and photosynthesis, which may impair photosynthesis and
      finally led to the seedling death in asl3 mutant. These results evidenced the
      important role of ASL3 in the early development of rice, especially chloroplast
      development. CONCLUSIONS: The ASL3 gene encoded a novel chloroplast-targeted PPR
      protein with 10 tandem PPR motifs in rice. Disruption of the ASL3 would lead to a
      defective chloroplast and seedling lethality, and affected expression levels of
      genes associated with chloroplast development and photosynthesis at early leaf
      stage of rice.

PMID- 25859291
TI  - Polycomb-mediated silencing in neuroendocrine prostate cancer.
AB  - BACKGROUND: Neuroendocrine prostate cancer (NEPC) is a highly aggressive subtype
      of prostate cancer (PCa) for which the median survival remains less than a year.
      Current treatments are only palliative in nature, and the lack of suitable pre
      clinical models has hampered previous efforts to develop novel therapeutic
      strategies. Addressing this need, we have recently established the first in vivo
      model of complete neuroendocrine transdifferentiation using patient-derived
      xenografts. Few genetic differences were observed between parental PCa and
      relapsed NEPC, suggesting that NEPC likely results from alterations that are
      epigenetic in nature. Thus, we sought to identify targetable epigenetic
      regulators whose expression was elevated in NEPC using genome-wide profiling of
      patient-derived xenografts and clinical samples. RESULTS: Our data indicate that
      multiple members of the polycomb group (PcG) family of transcriptional repressors
      were selectively upregulated in NEPC. Notably, CBX2 and EZH2 were consistently
      the most highly overexpressed epigenetic regulators across multiple datasets from
      clinical and xenograft tumor tissues. Given the striking upregulation of PcG
      genes and other transcriptional repressors, we derived a 185-gene list termed
      'neuroendocrine-associated repression signature' (NEARS) by overlapping
      transcripts downregulated across multiple in vivo NEPC models. In line with the
      striking upregulation of PcG family members, NEARS was preferentially enriched
      with PcG target genes, suggesting a driving role for PcG silencing in NEPC.
      Importantly, NEARS was significantly associated with high-grade tumors,
      metastatic progression, and poor outcome in multiple clinical datasets,
      consistent with extensive literature linking PcG genes and aggressive disease
      progression. CONCLUSIONS: We have explored the epigenetic landscape of NEPC and
      provided evidence of increased PcG-mediated silencing associated with aberrant
      transcriptional regulation of key differentiation genes. Our results position
      CBX2 and EZH2 as potential therapeutic targets in NEPC, providing opportunities
      to explore novel strategies aimed at reversing epigenetic alterations driving
      this lethal disease.

PMID- 25859293
TI  - 7T Multi-shell Hybrid Diffusion Imaging (HYDI) for Mapping Brain Connectivity in
      Mice.
AB  - Diffusion weighted imaging (DWI) is widely used to study microstructural
      characteristics of the brain. High angular resolution diffusion imaging (HARDI)
      samples diffusivity at a large number of spherical angles, to better resolve
      neural fibers that mix or cross. Here, we implemented a framework for advanced
      mathematical analysis of mouse 5-shell HARDI (b=1000, 3000, 4000, 8000, 12000
      s/mm2), also known as hybrid diffusion imaging (HYDI). Using q-ball imaging (QBI)
      at ultra-high field strength (7 Tesla), we computed diffusion and fiber
      orientation distribution functions (dODF, fODF) to better detect crossing fibers.
      We also computed a quantitative anisotropy (QA) index, and deterministic
      tractography, from the peak orientation of the fODFs. We found that the signal to
      noise ratio (SNR) of the QA was significantly higher in single and multi-shell
      reconstructed data at the lower b-values (b=1000, 3000, 4000 s/mm2) than at
      higher b-values (b=8000, 12000 s/mm2); the b=1000 s/mm2 shell increased the SNR
      of the QA in all multi-shell reconstructions, but when used alone or in <5-shell
      reconstruction, it led to higher angular error for the major fibers, compared to
      5-shell HYDI. Multi-shell data reconstructed major fibers with less error than
      single-shell data, and was most successful at reducing the angular error when the
      lowest shell was excluded (b=1000 s/mm2). Overall, high-resolution connectivity
      mapping with 7T HYDI offers great potential for understanding unresolved changes
      in mouse models of brain disease.

PMID- 25859294
TI  - Robust motion correction and outlier rejection of in vivo functional MR images of
      the fetal brain and placenta during maternal hyperoxia.
AB  - Subject motion is a major challenge in functional magnetic resonance imaging
      studies (fMRI) of the fetal brain and placenta during maternal hyperoxia. We
      propose a motion correction and volume outlier rejection method for the
      correction of severe motion artifacts in both fetal brain and placenta. The
      method is optimized to the experimental design by processing different phases of
      acquisition separately. It also automatically excludes high-motion volumes and
      all the missing data are regressed from ROI-averaged signals. The results
      demonstrate that the proposed method is effective in enhancing motion correction
      in fetal fMRI without large data loss, compared to traditional motion correction
      methods.

PMID- 25859295
TI  - Opioid dependence and substitution therapy: thymoquinone as potential novel
      supplement therapy for better outcome for methadone maintenance therapy
      substitution therapy.
AB  - Methadone is widely being used for opioid substitution therapy. However, the
      administration of methadone to opioid dependent individual is frequently
      accompanied by withdrawal syndrome and chemical dependency develops. Other than
      that, it is also difficult to retain patients in the treatment programme making
      their retention rates are decreasing over time. This article is written to
      higlights the potential use of prophetic medicines, Nigella sativa, as a
      supplement for opioid dependent receiving methadone. It focuses on the potential
      role of N. sativa and its major active compound, Thymoquinone (TQ) as a calcium
      channel blocking agent to reduce withdrawal syndrome and opioid dependency. 

PMID- 25859296
TI  - Black cumin (Nigella sativa) and its constituent (thymoquinone): a review on
      antimicrobial effects.
AB  - Nigella sativa seeds have wide therapeutic effects and have been reported to have
      significant effects against many ailments such as skin diseases, jaundice,
      gastrointestinal problems, anorexia, conjunctivitis, dyspepsia, rheumatism,
      diabetes, hypertension, intrinsic hemorrhage, paralysis, amenorrhea, anorexia,
      asthma, cough, bronchitis, headache, fever, influenza and eczema. Thymoquinone
      (TQ) is one of the most active constituent and has different beneficial
      properties. Focus on antimicrobial effects, different extracts of N. sativa as
      well as TQ, have a broad antimicrobial spectrum including Gram-negative, Gram
      positive bacteria, viruses, parasites, schistosoma and fungi. The effectiveness
      of N. sativa seeds and TQ is variable and depends on species of target
      microorganisms. The present review paper tries to describe all antimicrobial
      activities that have been carried out by various researchers. 

PMID- 25859297
TI  - The relaxant effect of Nigella sativa on smooth muscles, its possible mechanisms
      and clinical applications.
AB  - Nigella sativa (N. sativa) is a spice plant which has been traditionally used for
      culinary and medicinal purposes. Different therapeutic properties including the
      beneficial effects on asthma and dyspnea, digestive and gynecology disorders have
      been described for the seeds of N. sativa. There is evidence of the relaxant
      effects of this plant and some of its constituents on different types of smooth
      muscle including rabbit aorta, rabbit jejunum and trachea. The relaxant effect of
      N. sativa could be of therapeutic importance such as bronchodilation in asthma,
      vasodilation in hypertension and therapeutic effect on digestive or urogenital
      disorders. Therefore in the present article, the relaxant effects of N. sativa
      and its constituents on smooth muscles and its possible mechanisms as well as
      clinical application of this effect were reviewed. 

PMID- 25859298
TI  - Thymoquinone: an emerging natural drug with a wide range of medical applications.
AB  - Nigella sativa has attracted healers in ancient civilizations and researchers in
      recent times. Traditionally, it has been used in different forms to treat many
      diseases including asthma, hypertension, diabetes, inflammation, cough,
      bronchitis, headache, eczema, fever, dizziness and influenza. Experimentally, it
      has been demonstrated that N. sativa extracts and the main constituent of their
      volatile oil, thymoquinone, possess antioxidant, anti-inflammatory and
      hepatoprotective properties. In this review we aimed at summarizing the most
      recent investigations related to a few and most important effects of
      thymoquinone. It is concluded that thymoquinone has evidently proved its activity
      as hepatoprotective, anti-inflammatory, antioxidant, cytotoxic and anti-cancer
      chemical, with specific mechanisms of action, which provide support to consider
      this compound as an emerging drug. Further research is required to make
      thymoquinone a pharmaceutical preparation ready for clinical trials. 

PMID- 25859299
TI  - The protective effect of Nigella sativa against liver injury: a review.
AB  - Nigella sativa (Family Ranunculaceae) is a widely used medicinal plant throughout
      the world. N. sativa is referred in the Middle East as a part of an overall
      holistic approach to health. Pharmacological properties of N. sativa including
      immune stimulant, hypotensive, anti-inflammatory, anti-cancer, antioxidant,
      hypoglycemic, spasmolytic and bronchodilator have been shown. Reactive oxygen
      species (ROS) and oxidative stress are known as the major causes of many diseases
      such as liver injury and many substances and drugs can induce oxidative damage by
      generation of ROS in the body. Many pharmacological properties of N. sativa are
      known to be attributed to the presence of thymoquinone and its antioxidant
      effects. Thymoquinone protects liver from injury via different mechanisms
      including inhibition of iron-dependent lipid peroxidation, elevation in total
      thiol content and glutathione level, radical scavengering, increasing the
      activity of quinone reductase, catalase, superoxide dismutase and glutathione
      transferase, inhibition of NF-kappaB activity and inhibition of both
      cyclooxygenase and lipoxygenase. Therefore, this review aimed to highlight the
      roles of ROS in liver diseases and the mechanisms of N. sativa in prevention of
      liver injury. 

PMID- 25859301
TI  - Alternative supplement for enhancement of reproductive health and metabolic
      profile among perimenopausal women: a novel role of Nigella sativa.
AB  - OBJECTIVES: The aim of this open label crossover study was to investigate the
      effects of Nigella sativa on reproductive health and metabolic profile of
      perimenopausal women in Rawang, Malaysia. MATERIALS AND METHODS: Sixty nine
      perimenopausal women aged 45 to 65 were allocated into the experimental group
      treated orally with 1600mg/day of encapsulated pure powdered N. sativa compared
      to control groups treated with placebo for 12 weeks. At the end of study,
      participants underwent washout period for fourteen days before being crossed over
      and continued for another cycle of treatment. Participants were abstained from
      taking any other drugs, herbal preparations or food supplements throughout the
      study. Body weight, height, waist circumference, blood pressure, biochemical
      parameters and hormonal levels were measured at baseline and at the end of
      experiment for both cycles. Face to face interview was carried out at baseline
      and every week to check for compliance, minimize dropouts and to record
      reproductive health and quality of life indicators using Greene climacteric and
      SF-36 instruments. RESULTS: The treatment groups in both cycles showed
      significant improvement with reference to low density lipoprotein cholesterol and
      blood glucose (P<0.05). There were no significant differences between groups in
      total cholesterol, high density lipoprotein and triglyceride concentration.
      Treatment with N. sativa induced a significant reduction of prevalence and
      severity of menopausal symptomsas well as significant improvement in some
      components of quality of life (P<0.05). CONCLUSION: These results suggested that
      treatment with N. sativa exert a therapeutic and protective effect by modifying
      weight gain, improving lipid profile and blood glucose as well as hormonal level
      which is believed to play an important role in the pathogenesis of metabolic
      syndrome during menopause.

PMID- 25859300
TI  - Cardio-protective and anti-cancer therapeutic potential of Nigella sativa.
AB  - Nigella sativa is the miraculous plant having a lot of nutritional and medicinal
      benefits, and attracts large number of nutrition and pharmacological researchers.
      N. sativa seed composition shows that it is the blessing of nature and it
      contains and many bioactive compounds like thymoquinone, alpha-hederin,
      alkaloids, flavonoids, antioxidants, fatty acids many other compounds that have
      positive effects on curing of different diseases. Several medicinal properties of
      N. sativa like its anti-cancer, anti-inflammatory, anti-diabetic, antioxidant
      activities and many others are well acknowledged. However, this article focuses
      on activity of N. sativa against cardiovascular diseases and cancer. For
      gathering required data the authors went through vast number of articles using
      search engines like Science direct, ELSEVIER, Pub Med, Willey on Line Library and
      Google scholar and the findings were classified on the basis of relevance of the
      topic and were reviewed in the article. N. sativa is rich source of different
      biologically active compounds and is found effective in controlling number of
      cardiovascular diseases and various cancers both in vivo and in vitro studies. 

PMID- 25859302
TI  - Effect of Nigella sativa on ischemia-reperfusion induced rat kidney damage.
AB  - OBJECTIVES: There are a few previously reported studies about the effect of
      Nigella sativa oil on renal ischemia-reperfusion injury (IRI). The aim of the
      present study was to test the hypothesis whether pre- or post-treatment with N.
      sativa hydroalcoholic extract (NSE) would reduce tissue injury and oxidative
      damages in a clinically relevant rat model of renal IRI. MATERIALS AND METHODS:
      IRI was induced by clamping of bilateral renal arteries for 40 min fallowed by
      reperfusion for 180 min. NSE was prepared in a Soxhlet extractor and
      administrated with doses of 150 mg/kg or 300 mg/kg at 1 hr before ischemia
      induction (P-150 and 300) or at the beginning of reperfusion phase (T-150 and
      300), via jugular catheter intravenously. The kidneys were then removed and
      subjected to biochemical analysis, comet assay or histopathological examination.
      RESULTS: The kidneys of untreated IRI rats had a higher histopathological score
      (P<0.001), while in P-150, as well as T-150 and T-300 groups tubular lesions
      significantly decreased (P<0.001). Pre- and post-treatment with NSE also resulted
      in a significant decrease in malondialdehyde (MDA) level (P<0.001) and DNA damage
      (P<0.001) that were increased by renal I/R injury. NSE treatment also
      significantly restore (P<0.01) the decrease in renal thiol content caused by IRI.
      CONCLUSION: The present study shows N. sativa extract has marked protective
      action against renal IRI, which may be partly due to its antioxidant effects.

PMID- 25859303
TI  - Combination of Nigella sativa with Glycyrrhiza glabra and Zingiber officinale
      augments their protective effects on doxorubicin-induced toxicity in h9c2 cells.
AB  - OBJECTIVES: The use of doxorubicin (DOX) is limited by its dose-dependent cardio
      toxicity in which reactive Oxygen Species (ROS) play an important role in the
      pathological process. The aim of this study was to evaluate the protective effect
      of three medicinal plants, Nigella sativa (N), Glycyrrhiza glabra (G) and
      Zingiber officinale (Z), and their combination (NGZ), against DOX-induced
      apoptosis and death in H9c2 cells. MATERIALS AND METHODS: The cells were
      incubated with different concentrations of each extract or NGZ for 4 hr which
      continued in the presence or absence of 5uM doxorubicin for 24 hr. Cell viability
      and the apoptotic rate were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyl tetrazolium (MTT) and propidium iodide (PI) staining assays,
      respectively. The level of ROS and lipid peroxidation were measured by
      fluorimetric methods. RESULTS: Treatment with doxorubicin increased ROS
      generation, enhanced malondialdehyde (MDA) formation, and induced apoptosis. Co
      treatment of the cells with each herb extract increased viability of cells dose
      dependently with a maximum protection effect of about 30%, and their potencies
      were N>G>Z. The combination of the threshold dose of each extract (NGZ) produced
      a similar effect, which was increased dose-dependently to a maximum protection of
      70%. These effects were correlated with the effects of NGZ on ROS and MDA.
      CONCLUSION: All of the extracts have some protective effects against DOX-induced
      toxicity in cardiomyocytes with similar efficacies, but with different potencies.
      However, NGZ produced much higher protective effect via reducing oxidative stress
      and inhibiting of apoptotic induction processes. Further investigations are
      needed to determine the effects of NGZ on DOX chemotherapy.

PMID- 25859304
TI  - In vitro lethal effects of various extracts of Nigella sativa seed on hydatid
      cyst protoscoleces.
AB  - OBJECTIVES: There are several scolicidal agents for inactivation of hydatid cyst
      protoscolices during surgery, but most of them are associated with adverse side
      effects such as sclerosing cholangitis and liver necrosis. The present study was
      aimed to evaluate scolicidal effects of various extracts of Nigella sativa seeds
      against protoscoleces of hydatid cyst in an in vitro model. MATERIALS AND
      METHODS: Protoscoleces were aseptically aspirated from naturally infected livers
      of sheep and goats. Various concentrations of the different extracts of N. sativa
      (5 to 50 mg/ml) were used for 5 to 60 min. Viability of protoscoleces was
      confirmed by 0.1% eosin staining. RESULTS: The findings exhibited that methanolic
      extract at the concentration of 50 mg/ml after 10 min of incubation, and aqueous
      extract at the concentration of 50 mg/ml after 30 min of incubation can kill 100%
      of protoscoleces. In addition, all of experiments revealed dose-dependent and
      also time-dependent scolicidal effect of various extracts of N. sativa on the
      protoscoleces of hydatid cyst. CONCLUSION: The results of the present study
      demonstrated that N. sativa may be a natural source for the production of new
      scolicidal agent for use in hydatid cyst surgery. However, further studies will
      be required to evaluate scolicidal effects of N. sativa in the in vivo model.

PMID- 25859305
TI  - Neuroprotective effect of thymoquinone in acrylamide-induced neurotoxicity in
      Wistar rats.
AB  - OBJECTIVES: Acrylamide (ACR) has broad applications in different industries. It
      also forms in food during heating process. Oxidative stress has a critical role
      in ACR-induced neurotoxicity in both in vitro and in vivo models; therefore, the
      aim of the current study was the evaluation of effects of thymoquinone, the main
      constituent of volatile oil from Nigella sativa seeds in ACR-induced
      neurotoxicity. MATERIALS AND METHODS: Male Wistar rats were treated with ACR (50
      mg/kg IP) alone or with thymoquinone (TQ) (2.5, 5, 10 mg/kg IP) for 11 days. Two
      protocols were used in this study, A: in this one TQ and ACR were used
      simultaneously, B: Administration of TQ was started 1 week before ACR treatment
      and continued during exposure to ACR. At the end of the treatment, behavioral
      index (gait score) was examined for rats. After that, rats were sacrificed and
      molondialdehyde (MDA) as a marker of lipid peroxidation and glutathione (GSH)
      content were determined in cerebral cortex. RESULTS: Exposure to ACR led to
      severe gait abnormalities and treatment with TQ significantly decreased
      abnormalities. Level of MDA was elevated in cerebral cortex after exposure to ACR
      while TQ treatment significantly and in a dose-dependent manner reduced lipid
      peroxidation. Results clearly showed that there is no significant difference
      between two protocols of administration of TQ. CONCLUSION: It suggests the
      neuroprotective effect of TQ in this model in part, may be because of due the
      antioxidant activity of this natural compound.

PMID- 25859306
TI  - Thymoquinone, the main constituent of Nigella sativa, affects adenosine receptors
      in asthmatic guinea pigs.
AB  - OBJECTIVES: For determining the mechanism of anti-asthmatic effect of
      thymoquinone, this investigation evaluated the effect of thymoquinone in the
      presence of selective A2A and A2B adenosine receptor antagonists (ZM241385 and
      MRS1706, respectively). MATERIALS AND METHODS: Seventy guinea pigs were randomly
      divided to 7 groups; control (C), sensitized with ovalbumin (S), sensitized
      groups pretreated with thymoquinone (S+TQ), ZM241385 (S+Anta A2A), MRS1706
      (S+Anta A2B), thymoquinone and antagonists (S+Anta A2A+TQ and S+Anta A2B+TQ).
      Thymoquinone and each of these antagonists with 3 mg/kg dose were injected i.p.
      on 10(th) day of sensitization protocol. Tracheal responsiveness (TR) to
      methacholine and ovalbumin (OA), and total and differential cell count in lung
      lavage fluid (LLF) in different groups were measured. RESULTS: Increased EC50 and
      LLF neutrophil count and decreased TR to methacholine and OA, LLF eosinophil and
      basophil counts were observed in S+TQ group compared to S group (P<0.001 to
      P<0.05). Significant decrease in EC50 (P<0.01), LLF neutrophil, lymphocyte and
      monocyte count (P<0.001 for all) and significant increase in TR to OA (P<0.01),
      LLF total WBC (P<0.01) and eosinophil count (P<0.001) were observed in S+A2A
      group compared to S+TQ group. There was significant increase in LLF eosinophil
      and monocyte counts in S+Anta A2B group compared with S+TQ group (P<0.001 for
      both). In S+TQ+Anta A2A group, there was significant increase in LLF eosinophil
      (P<0.001) and significant decrease in LLF neutrophil (P<0.01) and monocyte
      (P<0.001) counts compared with S+TQ group. CONCLUSION: Thymoquinone affects
      adenosine receptors, which suggest that some of its anti-inflammatory effects may
      be mediated by these receptors.

PMID- 25859307
TI  - Effect of Nigella sativa fixed oil on ethanol toxicity in rats.
AB  - OBJECTIVES: This study was planned to appraise the protective effect of Nigella
      sativa fixed oil (NSO) against subchronic ethanol induced toxicity in rats.
      MATERIALS AND METHODS: Studies were carried out on six groups of six animals
      each, including control (normal saline, gavage), ethanol (3 g/kg/day, gavage),
      NSO (0.125, 0.25 and 0.5 ml/Kg/day, IP) plus ethanol and NSO (0.5 ml/Kg/day, IP)
      groups. Treatments were continued for 4 weeks. RESULTS: According to data,
      treatment with NSO attenuated ethanol-induced increased levels of malondialdehyde
      (MDA), tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6), as well
      as histopathological changes in liver and kidney tissues. Moreover, NSO improved
      the level of serum liver enzymes (including alanine transaminase (ALT), aspartate
      transaminase (AST), alkaline phosphatase (ALP) and glutathione (GSH) content in
      liver and kidney tissues in ethanol-treated rats. Western blot analysis and
      quantitative real time RT-PCR showed that NSO treatment inhibited apoptosis
      stimulated by ethanol through decreasing the Bax/Bcl-2 ratio (both protein and
      mRNA levels), cleaved caspase-3, cleaved caspase-8 and cleaved caspase-9 level in
      liver and kidney. CONCLUSION: This study showed that NSO may have protective
      effects against hepatotoxicity and renal toxicity of ethanol by decreasing lipid
      peroxidation and inflammation and preventing apoptosis.

PMID- 25859308
TI  - The Efficacy of Written Information Intervention in Reduction of Hospital Re
      admission Cost in Patients With Heart Failure; A Systematic Review and Meta
      Analysis.
AB  - OBJECTIVE: To assess the efficacy of written information versus non written
      information intervention in reducing hospital readmission cost, if prescribed or
      presented to the patients with HF. METHODS: The study was a systematic review and
      meta-analysis. We searched Medline (Ovid) and Cochrane library during the past 20
      years from 1993 to 2013. We also conducted a manual search through Google Scholar
      and a direct search in the group of related journals in Black Well and Science
      Direct trough their websites. Two reviewers appraised the identified studies, and
      meta-analysis was done to estimate the mean saving cost of patient readmission.
      All the included studies must have been done by randomization to be eligible for
      study. RESULT: We assessed the full-texts 3 out of 65 studies with 754 patients
      and average age of 74.33. The mean of estimated saving readmission cost in
      intervention group versus control group was US $2751 (95% CI: 2708 - 2794) and
      the mean of total saving cost in intervention group versus control group was US
      $2047 (base year 2010) with (95% CI: 2004 - 2089). No publication bias was found
      by testing the heterogeneity of studies. CONCLUSION: One of the effective factors
      in minimizing the healthcare cost and preventing from hospital re-admission is
      providing the patients with information prescription in a written format. It is
      suggested that hospital management, Medicare organizations, policy makers and
      individual physicians consider the prescription of appropriate medical
      information as the indispensable part of patient's care process.

PMID- 25859309
TI  - Duration analysis for coronary artery disease patients with chronic chest pain:
      an output from saudi arabia.
AB  - INTRODUCTION: Coronary artery disease (CAD) is a persistent public health problem
      worldwide. Chest pain is one of the perceptible symptoms of the same disease.
      Literature has found acute chest pain as plausible risk factors for CAD.
      Nevertheless, none of the study has estimated duration from chronic chest pain to
      the diagnosis of CAD. The objective of the study was to estimate duration from
      chronic chest pain to CAD and to assess impact of risk factors on same duration.
      METHODS: Data were obtained from community based study on 17,232 Saudi adults.
      History of patients about onset of chest pain and other risk factors were
      inquired. Descriptive measures were obtained by Kaplan-Meier curve. Effect of
      demographic and clinical factors was assessed by Cox regression models. RESULTS:
      Out of 24% patients with chest pain, 21% diagnosed with CAD. The average duration
      was 5 years. About 12% of patients with chest pain diagnosed with CAD after one
      year. Advancing age, female gender, no exercise and reduced high density
      lipoprotein (HDL) were significantly hazardous predictors throughout duration
      from chest pain to diagnosis of CAD. CONCLUSION: The duration from chest pain to
      CAD was 5 years. Age, gender, exercise and HDL can be variables of concern to
      deteriorate hazards of CAD for patients with chest pain.

PMID- 25859310
TI  - Effect of respiratory rehabilitation before open cardiac surgery on respiratory
      function: a randomized clinical trial.
AB  - INTRODUCTION: Prevention of pulmonary complications after coronary artery bypass
      graft is attended as a very important issue. The aim of this study was to
      evaluate the role of pulmonary rehabilitation before surgery for reducing the
      risk of pulmonary complications after surgery. METHODS: In a randomized clinical
      trial, 60 patients undergoing heart surgery were randomly divided into two groups
      A and B. Chest physiotherapy was performed before and after surgery on group A
      patients however it was done on group B's, only after surgery. Effects of
      preoperative pulmonary rehabilitation were compared between two groups, using
      spirometry and arterial blood gas (ABG). RESULTS: Thirty nine males (65%) and 21
      females (35%) with mean age of 8.10 +/- 9.56 were analyzed. The mean differences
      were statistically significant for predicted forced vital capacity (FVC) (CI
      95%:1.3 to 8.7) and Predicted Peak Flow indices (PEF) (CI 95%: 1.9 to 9.4) of
      spirometry indicator, PCO2 index (of ABG parameter) (CI 95%: 1.4 to 8.9) and mean
      oxygen saturation (mean Spo2) (CI 95%: 0.6 to 1.7) of ABG index in two groups.
      CONCLUSION: The performance of pulmonary rehabilitation program before surgery is
      recommended, as it may result in the reduction of complications of heart surgery.

PMID- 25859311
TI  - Predictors of post pericardiotomy low cardiac output syndrome in patients with
      pericardial effusion.
AB  - INTRODUCTION: Pathological involvement of pericardium by any disease that
      resulting in effusion may require decompression and pericardiectomy. The current
      article describes rare patients with effusion who after pericadiectomy and
      transient hemodynamic improvement rapidly developed progressive heart failure and
      subsequent multi organ failure. METHODS: During periods of five years, 423
      patients in our hospital underwent pericardiotomy for decompression of effusion.
      The clinical characteristics of those patient with postoperative low cardiac
      output (B group) (14 cases) recorded and compared with other patients without
      this postoperative complication (A group) by test and X2. Significant variables
      in invariables (P<=0.1) entered in logistic regression analysis and odd ratio of
      these significant variables obtained. RESULTS: Idiopathic pericardial effusion,
      malignancy, renal failure, connective tissue disease, viral pericarditis was
      found in 125 patients (27%), 105 patients (25.4%), 65 patients (15.6%), 50
      (17.1%) and 10 (2.4%) of patients subsequently. The factors that predict post
      operative death in logistic regression analysis were malignancy, radiotherapy,
      constrictive pericarditis inotropic drug using IABP using, pre-operative EF and
      pericardial calcification. CONCLUSION: Certain preoperative variables such as
      malignancy, radiotherapy, low EF, calcified pericardium and connective tissue
      disease are associated with POLCOS and post-operative risk of death. This
      paradoxical response to pericardial decompression may be more frequent than
      currently appreciated. Its cause may relate to the sudden removal of the chronic
      external ventricular support from the effusion or thicken pericardium resulting
      in ventricular dilatation and failure or intra operative myocardial injury due to
      pericardiectomy of calcified pericardium, radiation and cardiomyopathy.

PMID- 25859312
TI  - Relationship Between Prohormone Brain Natriuretic Peptide (NT-proBNP) Level and
      Severity of Pulmonary Dysfunction in Patients With Chronic Congestive Heart
      Failure.
AB  - INTRODUCTION: Congestive heart failure (CHF) is a common disease and its
      prevalence is increasing in industrialized countries. NT-proBNP measurement is an
      established diagnostic test for diagnosis of CHF in patients who present to
      emergency room with acute dyspnea. The primary object of this study was to
      determine the relationship between levels of brain natriuretic peptide precursor
      and severity of lung function impairment in patients with chronic CHF. METHODS:
      This cross-sectional and analytical study that performed in Tuberculosis and Lung
      Disease Research Center of Tabriz University of Medical Sciences on 95 patients
      with chronic heart failure, and relation between NT-proBNP levels and pulmonary
      function parameters were examined. RESULTS: Sixty-four patients were male and 31
      were female. The average age of male and females was 62.90 +/- 11.54 and 61.61 +/
      11.98 years, respectively. A significant inverse linear correlation was found
      between NT-proBNP and FEV1 (P < 0.001, r = -0.367), FVC (P < 0.001, r = -0.444),
      TLC (P = 0.022, r = -0.238), maximal midexpiratory flow (MMEF) (P = 0.047, r = 
      0.207) and left ventricular ejection fraction (LVEF) (P < 0.001, r = -0.461). A
      significant positive linear correlation was found between NT-proBNP and FEV1/FVC
      (P = 0.013, r = 0.257), RV/TLC (P = 0.003, r=0.303) and 5 Hz Raw (r = 0.231, P =
      0.024). CONCLUSION: This study showed that, both restrictive and obstructive
      ventilator impairments can occur in chronic CHF and as NT-proBNP increases
      appropriate to hemodynamic deterioration, pulmonary dysfunction increases.

PMID- 25859313
TI  - Comparison of the spo2/fio2 ratio and the pao2/fio2 ratio in patients with acute
      lung injury or acute respiratory distress syndrome.
AB  - INTRODUCTION: Diagnostic criteria for acute lung injury (ALI) and Acute
      Respiratory Distress syndrome (ARDS) includes acute onset of disease, chest
      radiograph demonstrating bilateral pulmonary infiltrates, lack of significant
      left ventricular dysfunction and Pao2/Fio2 (PF) ratio <=300 for ALI or <=200 for
      ARDS. Recent criteria require invasive arterial sampling. The pulse oximetric
      saturation Spo2/Fio2 (SF) ratio may be a reliable non-invasive alternative to the
      PF ratio. METHODS: In this cross-sectional study, we enrolled 70 patients with
      ALI or ARDS who were admitted in Tabriz children's hospital pediatrics intensive
      care unit (PICU). Spo2, Fio2, Pao2, charted within 5 minutes of each other and
      calculated SF and PF were recorded to determine the relationship between SF and
      PF ratio. SF values were examined as a substitute of PF ratio for diagnosis ARDS
      and ALI. RESULTS: The relationship between SF and PF ratio was described by the
      following regression equation: SF=57+0.61 PF (P<0.001). SF ratios of 181 and 235
      corresponded of PF ratio 300 and 200. The SF cutoff of 235 had 57% sensitivity
      and 100% specificity for diagnosis of ALI. The SF cutoff of 181 had 71%
      sensitivity and 82% specificity for diagnosis of ARDS. CONCLUSION: SF ratio is a
      reliable noninvasive surrogate for PF ratio to identify children with ALI or ARDS
      with the advantage of replacing invasive arterial blood sampling by non-invasive
      pulse oximetry.

PMID- 25859314
TI  - The effects of percutaneous mitral balloon valvuloplasty on the left atrial
      appendage function in patients with sinus rhythm and atrial fibrillation.
AB  - INTRODUCTION: Mitral stenosis (MS) causes structural and functional abnormalities
      of the left atrium (LA) and left atrial appendage (LAA), and studies show that
      LAA performance improves within a short time after percutaneous transvenous
      mitral commissurotomy (PTMC). This study aimed to investigate the effects of PTMC
      on left atrial function by transesophageal echocardiography (TEE). METHODS: We
      enrolled 56 patients with severe mitral stenosis (valve area less than 1.5
      CM(2)). All participants underwent mitral valvuloplasty; they also underwent
      transesophageal echocardiography before and at least one month after PTMC.
      RESULTS: Underlying heart rhythm was sinus rhythm (SR) in 28 patients and atrial
      fibrillation (AF) in remainder 28 cases. There was no significant change in the
      left ventricular ejection fraction (LVEF), left ventricular end diastolic
      dimension (LVEDD), or the left ventricular end systolic dimension (LVESD) before
      and after PTMC in both groups. However, both groups showed a significant decrease
      in the left atrial volume index (LAVI) following PTMC (P=0.032 in SR and P=0.015
      in AF group). LAA ejection fraction (LAAEF) and the LAA emptying velocity (LAAEV)
      were improved significantly after PTMC in both groups with SR and AF (P<0.001 for
      both). CONCLUSION: Percutaneous transvenous mitral commissurotomy improves left
      atrial appendage function in patients with mitral stenosis irrespective of the
      underlying heart rhythm.

PMID- 25859315
TI  - Endovascular treatment of an aortic traumatic double rupture.
AB  - Traumatic thoracic aortic rupture is a life-threatening condition; aortic isthmus
      is the most common site of rupture, but in rare cases traumatic injury can
      localize elsewhere, such as at aortic arch or at the level of the diaphragm. In
      the past few years, endovascular treatment of traumatic aortic injury became a
      safe procedure, with lower mortality and complication, if compared with open
      surgery. We report a case of a 40-year-old-man admitted to emergency department
      after a violent car crash in which an aortic traumatic double rupture was
      successfully treated with two endovascular stent-grafts coverage. 

PMID- 25859316
TI  - Svensson class IV Ascending aortic dissection, often confused with penetrating
      ulcer.
AB  - TWe present the case of a 64 years old male patient who had recently suffered an
      infective aortic valve endocarditis (Streptococcus agalactiae) complicated by
      embolic arthritis of the right hip. Initial echocardiography revealed moderate
      aortic insufficiency developed on a tricuspid aortic valve with a small
      vegetation (5 mm * 4 mm) on the left coronary cusp. Furthermore, an aneurysmal
      dilatation of the ascending aorta (maximal diameter, 54 mm) was noted. Other
      heart valves and left ventricular function were considered normal. The patient
      completed a 4 weeks course of antibiotherapy, and the right hip arthritis was
      treated by drainage and synovectomy. The patient was subsequently referred to
      surgery on an outpatient basis for the aneurysm of the ascending aorta.
      Preoperative computed tomography showed localized aortic dissection of the
      tubular ascending aorta characterized by an intimal tear without medial hematoma
      but excentric bulging of the aortic wall. This lesion was initially considered a
      penetrating ulcer of the aortic wall The operative specimen allowed to make
      differential diagnosis with a penetrating aortic ulcer by showing that the lesion
      did not develop within an atherosclerotic plaque. However, downstream extension
      of the dissection was probably limited by the presence of transmural
      calcifications on its distal side. The patient underwent successful complete
      aortic root replacement using a stentless Freestyle bioprosthesis with Dacron
      graft extension as reported previously. 

PMID- 25859317
TI  - Point-of-care ultrasound of the diaphragm in a liver transplant patient with
      acute respiratory failure.
AB  - In some intensive care, nowadays, ultrasound diagnostics have become an extension
      of the physical examination (like a stethoscope). In this report, we discuss the
      case of an acute respiratory failure which arose immediately after the end of
      general anesthesia. An initial bedside ultrasound evaluation applying the 'BLUE
      protocol' showed no pathological changes capable of explaining the clinical
      picture; however, by evaluating also the right and left hemidiaphragms, we made a
      diagnosis of diaphragmatic dysfunction, which would probably have been difficult
      to diagnose without the aid of the diaphragm ultrasound. We therefore decided to
      avoid intubation, transfer the patient to the intensive care unit, and treat him
      conservatively with non-invasive ventilation only. To our knowledge, this is the
      first case report that has shown the usefulness of ultrasonography in detecting
      diaphragmatic dysfunction as a cause of acute respiratory failure with a
      subsequent change in patient management. The use of bedside ultrasonography
      provides practical functional information on the diaphragmatic function in
      patients with acute respiratory failure and can also be easily repeated if follow
      up is required. This feature is still held in little consideration, but it can
      affect the diagnosis and the treatment of critically ill patients. 

PMID- 25859318
TI  - School-Based Intervention: Evaluating the role of Water, Latrines and Hygiene
      Education on Trachoma and Intestinal Parasitic Infections in Ethiopia.
AB  - OBJECTIVE: We sought to evaluate the impact of a hygiene and sanitation
      intervention program among school-children to control active trachoma and
      intestinal parasitic infections. METHODS: This longitudinal epidemiologic study
      was conducted among 630 students in rural Ethiopia. Baseline and follow-up
      surveys were conducted to evaluate the impact of a three pronged intervention
      program i) constructing of ventilated improved pit latrines, ii) provision of
      clean drinking water, and iii) and hygiene education. Socio-demographic
      information was collected using a structured questionnaire. Presence of trachoma
      and intestinal parasitic infections were evaluated using standard procedures.
      RESULTS: At baseline 15% of students had active trachoma while 6.7% of them were
      found to have active trachoma post intervention (p<0.001). Similar improvements
      were noted for parasitic infections. At baseline 7% of students were reported to
      have helminthic infections and 30.2% protozoa infections. However, only 4% of
      students had any helminthic infection and 13.4% (p<0.001) of them were found to
      have any protozoa infection. Improvements were noted in students' knowledge and
      attitudes towards hygiene and sanitation. CONCLUSIONS: The results of our study
      demonstrated that provision of comprehensive and targeted sanitation intervention
      program was successful in reducing the burden of trachoma and intestinal
      parasitic infection among school children.

PMID- 25859320
TI  - Shifting ranges and conservation challenges for lemurs in the face of climate
      change.
AB  - Geospatial modeling is one of the most powerful tools available to conservation
      biologists for estimating current species ranges of Earth's biodiversity. Now,
      with the advantage of predictive climate models, these methods can be deployed
      for understanding future impacts on threatened biota. Here, we employ predictive
      modeling under a conservative estimate of future climate change to examine
      impacts on the future abundance and geographic distributions of Malagasy lemurs.
      Using distribution data from the primary literature, we employed ensemble species
      distribution models and geospatial analyses to predict future changes in species
      distributions. Current species distribution models (SDMs) were created within the
      BIOMOD2 framework that capitalizes on ten widely used modeling techniques. Future
      and current SDMs were then subtracted from each other, and areas of contraction,
      expansion, and stability were calculated. Model overprediction is a common issue
      associated Malagasy taxa. Accordingly, we introduce novel methods for
      incorporating biological data on dispersal potential to better inform the
      selection of pseudo-absence points. This study predicts that 60% of the 57
      species examined will experience a considerable range of reductions in the next
      seventy years entirely due to future climate change. Of these species, range
      sizes are predicted to decrease by an average of 59.6%. Nine lemur species (16%)
      are predicted to expand their ranges, and 13 species (22.8%) distribution sizes
      were predicted to be stable through time. Species ranges will experience severe
      shifts, typically contractions, and for the majority of lemur species, geographic
      distributions will be considerably altered. We identify three areas in dire need
      of protection, concluding that strategically managed forest corridors must be a
      key component of lemur and other biodiversity conservation strategies. This
      recommendation is all the more urgent given that the results presented here do
      not take into account patterns of ongoing habitat destruction relating to human
      activities. 

PMID- 25859319
TI  - A requirement for hedgehog signaling in thyroid hormone-induced postembryonic
      intestinal remodeling.
AB  - BACKGROUND: Intestinal remodeling during amphibian metamorphosis has long been
      studied as a model for the formation of the adult organs in vertebrates,
      especially the formation of adult organ-specific stem cells. Like all other
      processes during metamorphosis, this process is controlled by thyroid hormone
      (T3), which affects cell fate and behavior through transcriptional regulation of
      target genes by binding to T3 receptors (TRs). Earlier studies have shown that
      Sonic hedgehog (Shh) is induced by T3 in the developing adult stem cells and that
      the Shh receptor and other downstream components are present in the connective
      tissue and at lower levels in the muscles at the climax of intestinal remodeling.
      However, no in vivo studies have carried out to investigate whether Shh produced
      in the adult cells can regulate the connective tissue to promote intestinal
      maturation. RESULTS: We have addressed this issue by treating tadpoles with Shh
      inhibitor cyclopamine. We showed that cyclopamine but not the structurally
      related chemical tomatidine inhibited the expression of Shh response genes BMP4,
      Snai2, and Twist1. More importantly, we showed that cyclopamine reduced the cell
      proliferation of both the developing adult stem cells as well as cells in the
      other intestinal tissues at the climax of metamorphosis, leading to
      delayed/incomplete remodeling of the intestine at the end of metamorphosis. We
      further revealed that both Snai2 and Twist1 were strongly upregulated during
      metamorphosis in the intestine and their expression was restricted to the
      connective tissue. CONCLUSIONS: Our results suggest that Shh indeed signals the
      connective tissue whereby it can increase adult stem cell proliferation and
      promote formation of the adult intestine.

PMID- 25859321
TI  - No-tillage and fertilization management on crop yields and nitrate leaching in
      North China Plain.
AB  - A field experiment was performed from 2003 to 2008 to evaluate the effects of
      tillage system and nitrogen management regimes on crop yields and nitrate
      leaching from the fluvo-aquic soil with a winter wheat (Triticum aestivum L.)
      maize (Zea mays L.) double-cropping system. The tillage systems consisted of
      conventional tillage (CT) and no-tillage (NT). Three nitrogen management regimes
      were included: 270 kg N ha(-1) of urea for wheat and 225 kg N ha(-1) of urea for
      maize (U), 180 kg N ha(-1) of urea and 90 kg N ha(-1) of straw for wheat and 180
      kg N of urea and 45 kg N ha(-1) of straw for maize (S), 180 kg N ha(-1) of urea
      and 90 kg N ha(-1) of manure for wheat and 180 kg N ha(-1) of urea and 45 kg N
      ha(-1) of manure for maize (M). An array of tension-free pan lysimeters (50 cm *
      75 cm) were installed (1.2 m deep) to measure water flow and [Formula: see text]
      N movement. No significant effect of the N management regime on yields of winter
      wheat and maize grain was found in the 5-year rotation. Tillage systems had
      significant influences on [Formula: see text]-N leaching from the second year and
      thereafter interacted with N management regimes on [Formula: see text]-N loads
      during all maize seasons. The average yield-scaled [Formula: see text]-N leaching
      losses were in order of CTS < NTS< CTU < NTU <CTM < NTM, ranging from 0.88 (CTS)
      to 6.07 (NTM) kg N Mg(-1) for winter wheat system and from 0.99 (CTS) to 6.27
      (NTM) kg N Mg(-1) for summer maize system for 5 rotation years. The results
      showed that CTS decreased the yield-scaled [Formula: see text]-N leaching losses
      while sustaining crop grain yields. Considering the lower costs, NTS could be a
      potential alternative to decrease yield-scaled [Formula: see text]-N leaching
      losses and improve soil fertility while maintaining crop yield for the winter
      wheat-maize double-cropping systems in the North China Plain. 

PMID- 25859322
TI  - The effect of developmental nutrition on life span and fecundity depends on the
      adult reproductive environment in Drosophila melanogaster.
AB  - Both developmental nutrition and adult nutrition affect life-history traits;
      however, little is known about whether the effect of developmental nutrition
      depends on the adult environment experienced. We used the fruit fly to determine
      whether life-history traits, particularly life span and fecundity, are affected
      by developmental nutrition, and whether this depends on the extent to which the
      adult environment allows females to realize their full reproductive potential. We
      raised flies on three different developmental food levels containing increasing
      amounts of yeast and sugar: poor, control, and rich. We found that development on
      poor or rich larval food resulted in several life-history phenotypes indicative
      of suboptimal conditions, including increased developmental time, and, for poor
      food, decreased adult weight. However, development on poor larval food actually
      increased adult virgin life span. In addition, we manipulated the reproductive
      potential of the adult environment by adding yeast or yeast and a male. This
      manipulation interacted with larval food to determine adult fecundity.
      Specifically, under two adult conditions, flies raised on poor larval food had
      higher reproduction at certain ages - when singly mated this occurred early in
      life and when continuously mated with yeast this occurred during midlife. We show
      that poor larval food is not necessarily detrimental to key adult life-history
      traits, but does exert an adult environment-dependent effect, especially by
      affecting virgin life span and altering adult patterns of reproductive
      investment. Our findings are relevant because (1) they may explain differences
      between published studies on nutritional effects on life-history traits; (2) they
      indicate that optimal nutritional conditions are likely to be different for
      larvae and adults, potentially reflecting evolutionary history; and (3) they urge
      for the incorporation of developmental nutritional conditions into the central
      life-history concept of resource acquisition and allocation. 

PMID- 25859323
TI  - Stress relief may promote the evolution of greater phenotypic plasticity in
      exotic invasive species: a hypothesis.
AB  - Invasion ecologists have often found that exotic invaders evolve to be more
      plastic than conspecific populations from their native range. However, an open
      question is why some exotic invaders can even evolve to be more plastic given
      that there may be costs to being plastic. Investigation into the benefits and
      costs of plasticity suggests that stress may constrain the expression of
      plasticity (thereby reducing the benefits of plasticity) and exacerbate the costs
      of plasticity (although this possibility might not be generally applicable).
      Therefore, evolution of adaptive plasticity is more likely to be constrained in
      stressful environments. Upon introduction to a new range, exotic species may
      experience more favorable growth conditions (e.g., because of release from
      natural enemies). Therefore, we hypothesize that any factors mitigating stress in
      the introduced range may promote exotic invaders to evolve increased adaptive
      plasticity by reducing the costs and increasing the benefits of plasticity.
      Empirical evidence is largely consistent with this hypothesis. This hypothesis
      contributes to our understanding of why invasive species are often found to be
      more competitive in a subset of environments. Tests of this hypothesis may not
      only help us understand what caused increased plasticity in some exotic invaders,
      but could also tell us if costs (unless very small) are more likely to inhibit
      the evolution of adaptive plasticity in stressful environments in general. 

PMID- 25859324
TI  - Potential for adaptive evolution at species range margins: contrasting
      interactions between red coral populations and their environment in a changing
      ocean.
AB  - Studying population-by-environment interactions (PEIs) at species range margins
      offers the opportunity to characterize the responses of populations facing an
      extreme regime of selection, as expected due to global change. Nevertheless, the
      importance of these marginal populations as putative reservoirs of adaptive
      genetic variation has scarcely been considered in conservation biology. This is
      particularly true in marine ecosystems for which the deep refugia hypothesis
      proposes that disturbed shallow and marginal populations of a given species can
      be replenished by mesophotic ones. This hypothesis therefore assumes that
      identical PEIs exist between populations, neglecting the potential for adaptation
      at species range margins. Here, we combine reciprocal transplant and common
      garden experiments with population genetics analyses to decipher the PEIs in the
      red coral, Corallium rubrum. Our analyses reveal partially contrasting PEIs
      between shallow and mesophotic populations separated by approximately one hundred
      meters, suggesting that red coral populations may potentially be locally adapted
      to their environment. Based on the effective population size and connectivity
      analyses, we posit that genetic drift may be more important than gene flow in the
      adaptation of the red coral. We further investigate how adaptive divergence could
      impact population viability in the context of warming and demonstrate
      differential phenotypic buffering capacities against thermal stress. Our study
      questions the relevance of the deep refugia hypothesis and highlights the
      conservation value of marginal populations as a putative reservoir of adaptive
      genetic polymorphism. 

PMID- 25859325
TI  - Tree height-diameter allometry across the United States.
AB  - The relationship between tree height and diameter is fundamental in determining
      community and ecosystem structure as well as estimates of biomass and carbon
      storage. Yet our understanding of how tree allometry relates to climate and whole
      organismal function is limited. We used the Forest Inventory and Analysis
      National Program database to determine height-diameter allometries of 2,976,937
      individuals of 293 tree species across the United States. The shape of the
      allometric relationship was determined by comparing linear and nonlinear
      functional forms. Mixed-effects models were used to test for allometric
      differences due to climate and floristic (between angiosperms and gymnosperms)
      and functional groups (leaf habit and shade tolerance). Tree allometry
      significantly differed across the United States largely because of climate.
      Temperature, and to some extent precipitation, in part explained tree allometric
      variation. The magnitude of allometric variation due to climate, however, had a
      phylogenetic signal. Specifically, angiosperm allometry was more sensitive to
      differences in temperature compared to gymnosperms. Most notably, angiosperm
      height was more negatively influenced by increasing temperature variability,
      whereas gymnosperm height was negatively influenced by decreasing precipitation
      and increasing altitude. There was little evidence to suggest that shade
      tolerance influenced tree allometry except for very shade-intolerant trees which
      were taller for any given diameter. Tree allometry is plastic rather than fixed
      and scaling parameters vary around predicted central tendencies. This allometric
      variation provides insight into life-history strategies, phylogenetic history,
      and environmental limitations at biogeographical scales. 

PMID- 25859326
TI  - Natural selection for earlier male arrival to breeding grounds through direct and
      indirect effects in a migratory songbird.
AB  - For migratory birds, the earlier arrival of males to breeding grounds is often
      expected to have fitness benefits. However, the selection differential on male
      arrival time has rarely been decomposed into the direct effect of male arrival
      and potential indirect effects through female traits. We measured the directional
      selection differential on male arrival time in the pied flycatcher (Ficedula
      hypoleuca) using data from 6 years and annual number of fledglings as the fitness
      proxy. Using structural equation modeling, we were able to take into account the
      temporal structure of the breeding cycle and the hierarchy between the examined
      traits. We found directional selection differentials for earlier male arrival
      date and earlier female laying date, as well as strong selection differential for
      larger clutch size. These selection differentials were due to direct selection
      only as indirect selection for these traits was nonsignificant. When decomposing
      the direct selection for earlier male arrival into direct and indirect effects,
      we discovered that it was almost exclusively due to the direct effect of male
      arrival date on fitness and not due to its indirect effects via female traits. In
      other words, we showed for the first time that there is a direct effect of male
      arrival date on fitness while accounting for those effects that are mediated by
      effects of the social partner. Our study thus indicates that natural selection
      directly favored earlier male arrival in this flycatcher population. 

PMID- 25859327
TI  - Mitochondrial genetic differentiation and morphological difference of Miniopterus
      fuliginosus and Miniopterus magnater in China and Vietnam.
AB  - Because of its complicated systematics, the bent-winged bat is one of the most
      frequently studied bat species groups. In China, two morphologically similar bent
      winged bat species, Miniopterus fuliginosus and Miniopterus magnater were
      identified, but their distribution range and genetic differentiation are largely
      unexplored. In this study, we applied DNA bar codes and two other mitochondrial
      DNA genes including morphological parameters to determine the phylogeny, genetic
      differentiation, spatial distribution, and morphological difference of the M.
      fuliginosus and M. magnater sampled from China and one site in Vietnam.
      Mitochondrial DNA gene genealogies revealed two monophyletic lineages throughout
      the Tropic of Cancer. According to DNA bar code divergences, one is M.
      fuliginosus corresponding to the Chinese mainland and the other is M. magnater
      corresponding to tropical regions including Hainan and Guangdong provinces of
      China and Vietnam. Their most recent common ancestor was dated to the early stage
      of the Quaternary glacial period (ca. 2.26 million years ago [Ma] on the basis of
      D-loop data, and ca. 1.69-2.37 Ma according to ND2). A population expansion event
      was inferred for populations of M. fuliginosus at 0.14 Ma. The two species
      probably arose in separate Pleistocene refugia under different climate zones.
      They significantly differed in forearm length, maxillary third molar width, and
      greatest length of the skull. 

PMID- 25859328
TI  - Ecological differentiation, lack of hybrids involving diploids, and asymmetric
      gene flow between polyploids in narrow contact zones of Senecio carniolicus (syn.
      Jacobaea carniolica, Asteraceae).
AB  - Areas of immediate contact of different cytotypes offer a unique opportunity to
      study evolutionary dynamics within heteroploid species and to assess isolation
      mechanisms governing coexistence of cytotypes of different ploidy. The degree of
      reproductive isolation of cytotypes, that is, the frequency of heteroploid
      crosses and subsequent formation of viable and (partly) fertile hybrids, plays a
      crucial role for the long-term integrity of lineages in contact zones. Here, we
      assessed fine-scale distribution, spatial clustering, and ecological niches as
      well as patterns of gene flow in parental and hybrid cytotypes in zones of
      immediate contact of di-, tetra-, and hexaploid Senecio carniolicus (Asteraceae)
      in the Eastern Alps. Cytotypes were spatially separated also at the investigated
      microscale; the strongest spatial separation was observed for the fully
      interfertile tetra- and hexaploids. The three main cytotypes showed highly
      significant niche differences, which were, however, weaker than across their
      entire distribution ranges in the Eastern Alps. Individuals with intermediate
      ploidy levels were found neither in the diploid/tetraploid nor in the
      diploid/hexaploid contact zones indicating strong reproductive barriers. In
      contrast, pentaploid individuals were frequent in the tetraploid/hexaploid
      contact zone, albeit limited to a narrow strip in the immediate contact zone of
      their parental cytotypes. AFLP fingerprinting data revealed introgressive gene
      flow mediated by pentaploid hybrids from tetra- to hexaploid individuals, but not
      vice versa. The ecological niche of pentaploids differed significantly from that
      of tetraploids but not from hexaploids. 

PMID- 25859330
TI  - Distance measures and optimization spaces in quantitative fatty acid signature
      analysis.
AB  - Quantitative fatty acid signature analysis has become an important method of diet
      estimation in ecology, especially marine ecology. Controlled feeding trials to
      validate the method and estimate the calibration coefficients necessary to
      account for differential metabolism of individual fatty acids have been conducted
      with several species from diverse taxa. However, research into potential
      refinements of the estimation method has been limited. We compared the
      performance of the original method of estimating diet composition with that of
      five variants based on different combinations of distance measures and
      calibration-coefficient transformations between prey and predator fatty acid
      signature spaces. Fatty acid signatures of pseudopredators were constructed using
      known diet mixtures of two prey data sets previously used to estimate the diets
      of polar bears Ursus maritimus and gray seals Halichoerus grypus, and their diets
      were then estimated using all six variants. In addition, previously published
      diets of Chukchi Sea polar bears were re-estimated using all six methods. Our
      findings reveal that the selection of an estimation method can meaningfully
      influence estimates of diet composition. Among the pseudopredator results, which
      allowed evaluation of bias and precision, differences in estimator performance
      were rarely large, and no one estimator was universally preferred, although
      estimators based on the Aitchison distance measure tended to have modestly
      superior properties compared to estimators based on the Kullback-Leibler distance
      measure. However, greater differences were observed among estimated polar bear
      diets, most likely due to differential estimator sensitivity to assumption
      violations. Our results, particularly the polar bear example, suggest that
      additional research into estimator performance and model diagnostics is
      warranted. 

PMID- 25859329
TI  - A comparative analysis reveals weak relationships between ecological factors and
      beta diversity of stream insect metacommunities at two spatial levels.
AB  - The hypotheses that beta diversity should increase with decreasing latitude and
      increase with spatial extent of a region have rarely been tested based on a
      comparative analysis of multiple datasets, and no such study has focused on
      stream insects. We first assessed how well variability in beta diversity of
      stream insect metacommunities is predicted by insect group, latitude, spatial
      extent, altitudinal range, and dataset properties across multiple drainage basins
      throughout the world. Second, we assessed the relative roles of environmental and
      spatial factors in driving variation in assemblage composition within each
      drainage basin. Our analyses were based on a dataset of 95 stream insect
      metacommunities from 31 drainage basins distributed around the world. We used
      dissimilarity-based indices to quantify beta diversity for each metacommunity
      and, subsequently, regressed beta diversity on insect group, latitude, spatial
      extent, altitudinal range, and dataset properties (e.g., number of sites and
      percentage of presences). Within each metacommunity, we used a combination of
      spatial eigenfunction analyses and partial redundancy analysis to partition
      variation in assemblage structure into environmental, shared, spatial, and
      unexplained fractions. We found that dataset properties were more important
      predictors of beta diversity than ecological and geographical factors across
      multiple drainage basins. In the within-basin analyses, environmental and spatial
      variables were generally poor predictors of variation in assemblage composition.
      Our results revealed deviation from general biodiversity patterns because beta
      diversity did not show the expected decreasing trend with latitude. Our results
      also call for reconsideration of just how predictable stream assemblages are
      along ecological gradients, with implications for environmental assessment and
      conservation decisions. Our findings may also be applicable to other dynamic
      systems where predictability is low. 

PMID- 25859331
TI  - Morphological and moisture availability controls of the leaf area-to-sapwood area
      ratio: analysis of measurements on Australian trees.
AB  - The leaf area-to-sapwood area ratio (LA:SA) is a key plant trait that links
      photosynthesis to transpiration. The pipe model theory states that the sapwood
      cross-sectional area of a stem or branch at any point should scale isometrically
      with the area of leaves distal to that point. Optimization theory further
      suggests that LA:SA should decrease toward drier climates. Although acclimation
      of LA:SA to climate has been reported within species, much less is known about
      the scaling of this trait with climate among species. We compiled LA:SA
      measurements from 184 species of Australian evergreen angiosperm trees. The pipe
      model was broadly confirmed, based on measurements on branches and trunks of
      trees from one to 27 years old. Despite considerable scatter in LA:SA among
      species, quantile regression showed strong (0.2 < R1 < 0.65) positive
      relationships between two climatic moisture indices and the lowermost (5%) and
      uppermost (5-15%) quantiles of log LA:SA, suggesting that moisture availability
      constrains the envelope of minimum and maximum values of LA:SA typical for any
      given climate. Interspecific differences in plant hydraulic conductivity are
      probably responsible for the large scatter of values in the mid-quantile range
      and may be an important determinant of tree morphology. 

PMID- 25859332
TI  - Demonstration of pollinator-mediated competition between two native Impatiens
      species, Impatiens noli-tangere and I. textori (Balsaminaceae).
AB  - Plant-plant interspecific competition via pollinators occurs when the flowering
      seasons of two or more plant species overlap and the pollinator fauna is shared.
      Negative sexual interactions between species (reproductive interference) through
      improper heterospecific pollen transfer have recently been reported between
      native and invasive species demonstrating pollination-driven competition. We
      focused on two native Impatiens species (I. noli-tangere and I. textori) found in
      Japan and examined whether pollinator-mediated plant competition occurs between
      them. We demonstrate that I. noli-tangere and I. textori share the same
      pollination niche (i.e., flowering season, pollinator fauna, and position of
      pollen on the pollinator's body). In addition, heterospecific pollen grains were
      deposited on most stigmas of both I. noli-tangere and I. textori flowers that
      were situated within 2 m of flowers of the other species resulting in depressed
      fruit set. Further, by hand-pollination experiments, we show that when as few as
      10% of the pollen grains are heterospecific, fruit set is decreased to less than
      half in both species. These results show that intensive pollinator-mediated
      competition occurs between I. noli-tangere and I. textori. This study suggests
      that intensive pollinator-mediated competition occurs in the wild even when
      interacting species are both native and not invasive. 

PMID- 25859333
TI  - Carbon and nitrogen isotope fractionation of amino acids in an avian marine
      predator, the gentoo penguin (Pygoscelis papua).
AB  - Compound-specific stable isotope analysis (CSIA) of amino acids (AA) has rapidly
      become a powerful tool in studies of food web architecture, resource use, and
      biogeochemical cycling. However, applications to avian ecology have been limited
      because no controlled studies have examined the patterns in AA isotope
      fractionation in birds. We conducted a controlled CSIA feeding experiment on an
      avian species, the gentoo penguin (Pygoscelis papua), to examine patterns in
      individual AA carbon and nitrogen stable isotope fractionation between diet (D)
      and consumer (C) (Delta(13)CC-D and Delta(15)NC-D, respectively). We found that
      essential AA delta (13)C values and source AA delta (15)N values in feathers
      showed minimal trophic fractionation between diet and consumer, providing
      independent but complimentary archival proxies for primary producers and nitrogen
      sources respectively, at the base of food webs supporting penguins. Variations in
      nonessential AA Delta(13)CC-D values reflected differences in macromolecule
      sources used for biosynthesis (e.g., protein vs. lipids) and provided a metric to
      assess resource utilization. The avian-specific nitrogen trophic discrimination
      factor (TDFGlu-Phe = 3.5 +/- 0.40/00) that we calculated from the difference in
      trophic fractionation (Delta(15)NC -D) of glutamic acid and phenylalanine was
      significantly lower than the conventional literature value of 7.60/00. Trophic
      positions of five species of wild penguins calculated using a multi-TDFG lu-Phe
      equation with the avian-specific TDFG lu-Phe value from our experiment provided
      estimates that were more ecologically realistic than estimates using a single
      TDFG lu-Phe of 7.60/00 from the previous literature. Our results provide a
      quantitative, mechanistic framework for the use of CSIA in nonlethal, archival
      feathers to study the movement and foraging ecology of avian consumers. 

PMID- 25859334
TI  - Drought-induced changes in flow regimes lead to long-term losses in mussel
      provided ecosystem services.
AB  - Extreme hydro-meteorological events such as droughts are becoming more frequent,
      intense, and persistent. This is particularly true in the south central USA,
      where rapidly growing urban areas are running out of water and human-engineered
      water storage and management are leading to broad-scale changes in flow regimes.
      The Kiamichi River in southeastern Oklahoma, USA, has high fish and freshwater
      mussel biodiversity. However, water from this rural river is desired by multiple
      urban areas and other entities. Freshwater mussels are large, long-lived filter
      feeders that provide important ecosystem services. We ask how observed changes in
      mussel biomass and community composition resulting from drought-induced changes
      in flow regimes might lead to changes in river ecosystem services. We sampled
      mussel communities in this river over a 20-year period that included two severe
      droughts. We then used laboratory-derived physiological rates and river-wide
      estimates of species-specific mussel biomass to estimate three aggregate
      ecosystem services provided by mussels over this time period: biofiltration,
      nutrient recycling (nitrogen and phosphorus), and nutrient storage (nitrogen,
      phosphorus, and carbon). Mussel populations declined over 60%, and declines were
      directly linked to drought-induced changes in flow regimes. All ecosystem
      services declined over time and mirrored biomass losses. Mussel declines were
      exacerbated by human water management, which has increased the magnitude and
      frequency of hydrologic drought in downstream reaches of the river. Freshwater
      mussels are globally imperiled and declining around the world. Summed across
      multiple streams and rivers, mussel losses similar to those we document here
      could have considerable consequences for downstream water quality although lost
      biofiltration and nutrient retention. While we cannot control the frequency and
      severity of climatological droughts, water releases from reservoirs could be used
      to augment stream flows and prevent compounded anthropogenic stressors. 

PMID- 25859335
TI  - The stress hormone corticosterone in a marine top predator reflects short-term
      changes in food availability.
AB  - In many seabird studies, single annual proxies of prey abundance have been used
      to explain variability in breeding performance, but much more important is
      probably the timing of prey availability relative to the breeding season when
      energy demand is at a maximum. Until now, intraseasonal variation in prey
      availability has been difficult to quantify in seabirds. Using a state-of-the-art
      ocean drift model of larval cod Gadus morhua, an important constituent of the
      diet of common guillemots Uria aalge in the southwestern Barents Sea, we were
      able to show clear, short-term correlations between food availability and
      measurements of the stress hormone corticosterone (CORT) in parental guillemots
      over a 3-year period (2009-2011). The model allowed the extraction of abundance
      and size of cod larvae with very high spatial (4 km) and temporal resolutions (1
      day) and showed that cod larvae from adjacent northern spawning grounds in Norway
      were always available near the guillemot breeding colony while those from more
      distant southerly spawning grounds were less frequent, but larger. The latter
      arrived in waves whose magnitude and timing, and thus overlap with the guillemot
      breeding season, varied between years. CORT levels in adult guillemots were lower
      in birds caught after a week with high frequencies of southern cod larvae. This
      pattern was restricted to the two years (2009 and 2010) in which southern larvae
      arrived before the end of the guillemot breeding season. Any such pattern was
      masked in 2011 by already exceptionally high numbers of cod larvae in the region
      throughout chick-rearing period. The findings suggest that CORT levels in
      breeding birds increase when the arrival of southern sizable larvae does not
      match the period of peak energy requirements during breeding. 

PMID- 25859336
TI  - A temperature shock can lead to trans-generational immune priming in the Red
      Flour Beetle, Tribolium castaneum.
AB  - Trans-generational immune priming (TGIP) describes the transfer of immune
      stimulation to the next generation. As stress and immunity are closely connected,
      we here address the question whether trans-generational effects on immunity and
      resistance can also be elicited by a nonpathogen stress treatment of parents.
      General stressors have been shown to induce immunity to pathogens within
      individuals. However, to our knowledge, it is as of yet unknown whether stress
      can also induce trans-generational effects on immunity and resistance. We exposed
      a parental generation (mothers, fathers, or both parents) of the red flour beetle
      Tribolium castaneum, a species where TGIP has been previously been demonstrated,
      to either a brief heat or cold shock and examined offspring survival after
      bacterial infection with the entomopathogen Bacillus thuringiensis. We also
      studied phenoloxidase activity, a key enzyme of the insect innate immune system
      that has previously been demonstrated to be up-regulated upon TGIP. We quantified
      parental fecundity and offspring developmental time to evaluate whether trans
      generational priming might have costs. Offspring resistance was found to be
      significantly increased when both parents received a cold shock. Offspring
      phenoloxidase activity was also higher when mothers or both parents were cold
      shocked. By contrast, parental heat shock reduced offspring phenoloxidase
      activity. Moreover, parental cold or heat shock delayed offspring development. In
      sum, we conclude that trans-generational priming for resistance could not only be
      elicited by pathogens or pathogen-derived components, but also by more general
      cues that are indicative of a stressful environment. The interaction between
      stress responses and the immune system might play an important role also for
      trans-generational effects. 

PMID- 25859337
TI  - Shade treatment affects structure and recovery of invasive C4 African grass
      Echinochloa pyramidalis.
AB  - Echinochloa pyramidalis (Lam.) Hitchc. & Chase is an African grass with C4
      photosynthesis, high biomass production, and high vegetative propagation that is
      tolerant to grazing and able to grow in flooded and dry conditions. Thus, it is
      highly invasive in tropical freshwater marshes where it is intentionally planted
      by ranchers to increase cattle production. This invasion is reducing plant
      biodiversity by increasing the invader's aerial coverage, changing wetland
      hydrology and causing soil physicochemical changes such as vertical accretion.
      Reducing the dominance of this species and increasing the density of native
      wetland species is a difficult, expensive, and time-consuming process. We applied
      a series of disturbance treatments aimed at eliminating E. pyramidalis and
      recovering the native vegetation of a partially invaded freshwater marsh.
      Treatments included physical (cutting, soil disking, transplanting individuals of
      the key native species Sagittaria lancifolia subsp. media (Micheli) Bogin, and/or
      reducing light with shade mesh) and/or chemical (spraying Round-UpTM herbicide)
      disturbances. At the end of the experiment, four of the five treatments used were
      effective in increasing the cover and biomass of native species and reducing that
      of E. pyramidalis. The combination of these treatments should be used to generate
      a proposal for the restoration of tropical wetlands invaded by non-native
      grasses. A promising treatment is using soil disked to soften the soil and
      destroy belowground structures such as roots and rhizomes. This treatment would
      be more promising if combined with the use of shade cloth. If it is desirable not
      to impact the soil or if there is not enough budget to make an effort to include
      active restoration disking soil, the use of shade cloth will suffice, although
      the recovery of native vegetation will be slower. 

PMID- 25859338
TI  - The evolution of plasticity of dauer larva developmental arrest in the nematode
      Caenorhabditis elegans.
AB  - Organisms can end up in unfavourable conditions and to survive this they have
      evolved various strategies. Some organisms, including nematodes, survive
      unfavourable conditions by undergoing developmental arrest. The model nematode
      Caenorhabditis elegans has a developmental choice between two larval forms, and
      it chooses to develop into the arrested dauer larva form in unfavourable
      conditions (specifically, a lack of food and high population density, indicated
      by the concentration of a pheromone). Wild C. elegans isolates vary extensively
      in their dauer larva arrest phenotypes, and this prompts the question of what
      selective pressures maintain such phenotypic diversity? To investigate this we
      grew C. elegans in four different environments, consisting of different
      combinations of cues that can induce dauer larva development: two combinations of
      food concentration (high and low) in the presence or absence of a dauer larva
      inducing pheromone. Five generations of artificial selection of dauer larvae
      resulted in an overall increase in dauer larva formation in most selection
      regimes. The presence of pheromone in the environment selected for twice the
      number of dauer larvae, compared with environments not containing pheromone.
      Further, only a high food concentration environment containing pheromone
      increased the plasticity of dauer larva formation. These evolutionary responses
      also affected the timing of the worms' reproduction. Overall, these results give
      an insight into the environments that can select for different plasticities of C.
      elegans dauer larva arrest phenotypes, suggesting that different combinations of
      environmental cues can select for the diversity of phenotypically plastic
      responses seen in C. elegans. 

PMID- 25859339
TI  - Landscape-scale accessibility of livestock to tigers: implications of spatial
      grain for modeling predation risk to mitigate human-carnivore conflict.
AB  - Innovative conservation tools are greatly needed to reduce livelihood losses and
      wildlife declines resulting from human-carnivore conflict. Spatial risk modeling
      is an emerging method for assessing the spatial patterns of predator-prey
      interactions, with applications for mitigating carnivore attacks on livestock.
      Large carnivores that ambush prey attack and kill over small areas, requiring
      models at fine spatial grains to predict livestock depredation hot spots. To
      detect the best resolution for predicting where carnivores access livestock, we
      examined the spatial attributes associated with livestock killed by tigers in
      Kanha Tiger Reserve, India, using risk models generated at 20, 100, and 200-m
      spatial grains. We analyzed land-use, human presence, and vegetation structure
      variables at 138 kill sites and 439 random sites to identify key landscape
      attributes where livestock were vulnerable to tigers. Land-use and human presence
      variables contributed strongly to predation risk models, with most variables
      showing high relative importance (>=0.85) at all spatial grains. The risk of a
      tiger killing livestock increased near dense forests and near the boundary of the
      park core zone where human presence is restricted. Risk was nonlinearly related
      to human infrastructure and open vegetation, with the greatest risk occurring 1.2
      km from roads, 1.1 km from villages, and 8.0 km from scrubland. Kill sites were
      characterized by denser, patchier, and more complex vegetation with lower
      visibility than random sites. Risk maps revealed high-risk hot spots inside of
      the core zone boundary and in several patches in the human-dominated buffer zone.
      Validation against known kills revealed predictive accuracy for only the 20 m
      model, the resolution best representing the kill stage of hunting for large
      carnivores that ambush prey, like the tiger. Results demonstrate that risk models
      developed at fine spatial grains can offer accurate guidance on landscape
      attributes livestock should avoid to minimize human-carnivore conflict. 

PMID- 25859341
TI  - Non-targeted metabolomics and lipidomics LC-MS data from maternal plasma of 180
      healthy pregnant women.
AB  - BACKGROUND: Metabolomics has the potential to be a powerful and sensitive
      approach for investigating the low molecular weight metabolite profiles present
      in maternal fluids and their role in pregnancy. FINDINGS: In this Data Note, LC
      MS metabolome, lipidome and carnitine profiling data were collected from 180
      healthy pregnant women, representing six time points spanning all three
      trimesters, and providing sufficient coverage to model the progression of normal
      pregnancy. CONCLUSIONS: As a relatively large scale, real-world dataset with
      robust numbers of quality control samples, the data are expected to prove useful
      for algorithm optimization and development, with the potential to augment studies
      into abnormal pregnancy. All data and ISA-TAB format enriched metadata are
      available for download in the MetaboLights and GigaScience databases.

PMID- 25859342
TI  - A genome draft of the legless anguid lizard, Ophisaurus gracilis.
AB  - BACKGROUND: Transition from a lizard-like to a snake-like body form is one of the
      most important transformations in reptilian evolution. The increasing number of
      sequenced reptilian genomes is enabling a deeper understanding of vertebrate
      evolution, although the genetic basis of the loss of limbs in reptiles remains
      enigmatic. Here we report genome sequencing, assembly, and annotation for the
      Asian glass lizard Ophisaurus gracilis, a limbless lizard species with an
      elongated snake-like body form. Addition of this species to the genome repository
      will provide an excellent resource for studying the genetic basis of limb loss
      and trunk elongation. FINDINGS: O. gracilis genome sequencing using the Illumina
      HiSeq2000 platform resulted in 274.20 Gbp of raw data that was filtered and
      assembled to a final size of 1.78 Gbp, comprising 6,717 scaffolds with N50 = 1.27
      Mbp. Based on the k-mer estimated genome size of 1.71 Gbp, the assembly appears
      to be nearly 100% complete. A total of 19,513 protein-coding genes were
      predicted, and 884.06 Mbp of repeat sequences (approximately half of the genome)
      were annotated. The draft genome of O. gracilis has similar characteristics to
      both lizard and snake genomes. CONCLUSIONS: We report the first genome of a
      lizard from the family Anguidae, O. gracilis. This supplements currently
      available genetic and genomic resources for amniote vertebrates, representing a
      major increase in comparative genome data available for squamate reptiles in
      particular.

PMID- 25859343
TI  - Peritoneal dialysis catheter placement by interventional radiologists.

PMID- 25859344
TI  - Endovascular renal denervation: a novel sympatholytic with relevance to chronic
      kidney disease.
AB  - Endovascular renal denervation (sympathectomy) is a novel procedure developed for
      the treatment of resistant hypertension. Evidence suggests that it reduces both
      afferent and efferent sympathetic nerve activity, which may offer clinical
      benefit over and above any blood pressure-lowering effect. Studies have shown
      objective improvements in left ventricular mass, ventricular function, central
      arterial stiffness, central haemodynamics, baroreflex sensitivity and arrhythmia
      frequency. Benefits have also been seen in insulin resistance, microalbuminuria
      and glomerular filtration rate. In chronic kidney disease, elevated sympathetic
      activity has been causally linked to disease progression and cardiovascular
      sequelae. Effecting a marked reduction in sympathetic hyperactivity may herald a
      significant step in the management of this and other conditions. In this in-depth
      review, the pathophysiology and clinical significance of the sympatholytic
      effects of endovascular renal denervation are discussed. 

PMID- 25859345
TI  - Nephrotoxicity of recent anti-cancer agents.
AB  - Cancer patients may develop a variety of kidney lesions that impair not only
      their immediate survival but also limit the adequate treatment of the underlying
      malignant process. This review summarizes the nephrotoxic potential of some of
      the most recently developed anti-cancer drugs, focusing on those interfering with
      the vascular endothelial growth factor and epidermal growth factor receptor
      pathways and mammalian target of rapamycin inhibitors. Thrombotic microangiopathy
      (haemolytic-uraemic syndrome), proteinuria, hypertension and magnesium depletion
      are the most common side effects. Also the risk for developing acute kidney
      injury in patients with advanced prostate cancer undergoing androgen deprivation
      therapy is discussed. 

PMID- 25859346
TI  - Radiological insertion of Tenckhoff catheters for peritoneal dialysis: a 1-year
      single-centre experience.
AB  - BACKGROUND: Peritoneal dialysis (PD) is an important home-based dialysis modality
      for patients with end-stage kidney disease (ESKD). The initiation of PD requires
      timely and skilled insertion of a Tenckhoff catheter (TC). At most centres, TCs
      are inserted laparoscopically by surgeons under general anaesthetic. This
      requires access to increasingly scarce surgical, anaesthetic and hospital
      inpatient resources. Radiological insertion of TCs performed as a day procedure
      under local anaesthetic allows for easier access to the TC insertion with reduced
      resource requirements. We report our 1-year experience following the introduction
      of this technique to our PD programme. METHODS: This is a retrospective review of
      the outcomes for all patients who had TCs inserted radiologically (percutaneously
      with the assistance of ultrasound and fluoroscopy) over the 12-month period from
      December 2011 to December 2012. Relevant patient demographics collected included
      age, gender, body mass index (BMI), previous abdominal surgery and cause of ESKD.
      Extended details of the insertion procedure were also obtained including length
      of stay, early complications and time to first use of the catheter for PD.
      RESULTS: Thirty Argyle(TM) Swan Neck TCs were inserted under radiological
      guidance during the study period. The mean age of patients was 56 (SD +/- 14).
      The male-to-female ratio was 2:1. The mean BMI was 25.7 (SD +/- 4.8). PD was the
      initial dialysis modality in 22 (73%) patients. Of the 30 patients, 14 (46.7%)
      had previously undergone extraperitoneal abdominal surgery. All catheters were
      inserted successfully as day cases except four patients (13.3%) who had catheters
      inserted during an inpatient hospital admission. Most catheters were not accessed
      for a minimum of 10 days to reduce the chance of exit site leakage, in two cases
      the catheters were used within 5 days without complication. There were no cases
      of peritonitis or exit site infection during the observation period. Catheter
      migration occurred in four patients (13.3%) but only one required surgical
      intervention. Minor pain issues were noted in six patients (20%) and bleeding
      around the exit site requiring suturing in two patients (6.7%). The introduction
      of this technique at our institution saw a 67% increase in the number of patients
      performing PD. CONCLUSIONS: Radiological insertion of TCs for PD provided
      improved access to catheter insertion in a timely manner with reduced resource
      requirements. Over the 12-month observation period we noted a high technical
      success rate with very few complications. Our study supports radiological
      insertion of TCs under local anaesthetic as a viable alternative to catheter
      insertion in theatre under general anaesthetic. The relative ease of radiological
      TC insertion has resulted in a significant increase in patient uptake of PD at
      our centre.

PMID- 25859347
TI  - Forty-four-hour interdialytic ambulatory blood pressure monitoring and
      cardiovascular risk in pediatric hemodialysis patients.
AB  - BACKGROUND: Children undergoing chronic hemodialysis are at risk of
      cardiovascular disease and often develop left ventricular hypertrophy (LVH).
      Twenty-four-hour ambulatory blood pressure monitoring (ABPM) is known to better
      predict cardiovascular morbidity than casual blood pressure (BP) measurement.
      Given the BP variability attributed to interdialytic fluid overload, 44-h ABPM
      should better delineate cardiovascular morbidity in pediatric hemodialysis
      patients. METHODS: In this cross-sectional study, 17 children (16.7 +/- 2.9
      years) on chronic hemodialysis underwent 44-h interdialytic ABPM and routine
      echocardiogram. Left ventricular mass index (LVMI) was calculated by height-based
      equation; LVH was defined as an LVMI in the >=95th percentile for height-age and
      gender. Hypertension was defined by the recommendations of the Fourth Report of
      the National High Blood Pressure Education Program for casual measurements, and
      by those of the American Heart Association for ABPM. RESULTS: Twenty-four
      percentage of patients were hypertensive by casual post-dialytic systolic BP,
      whereas 59% were hypertensive by ABPM. Eighty-eight percentage of patients had
      abnormal cardiac geometry: 53% had LVH. Thirty-five percentage (6 of 17) had
      masked hypertension, including four with abnormal cardiac geometry, of which,
      three had LVH. LVMI correlated with ABPM, but not with casual measurements.
      Strongest correlations with an increased LVMI were with 44-h diastolic BP: at
      night (r = 0.53, P = 0.03) and total load (r = 0.57, P = 0.02). LVH was similarly
      associated with 44-h nighttime BP: systolic (P = 0.02), diastolic (P = 0.01) and
      mean arterial (P = 0.01). CONCLUSIONS: Casual BP measurement underestimates
      hypertension in pediatric hemodialysis patients and does not correlate well with
      indicators of cardiovascular morbidity. In contrast, 44-h interdialytic ABPM
      better characterizes hypertension, with nighttime parameters most strongly
      predicting increased LVMI and LVH.

PMID- 25859348
TI  - Increased risk of death in African American patients with end-stage renal disease
      secondary to lupus.
AB  - BACKGROUND: Systemic lupus erythematosus (SLE) is a devastating systemic disease
      that can lead to end-stage renal disease (ESRD). Our goal was to assess the
      relative mortality risk associated with race in pediatric and adult populations
      with ESRD secondary to SLE maintained on hemodialysis (HD). METHODS: We
      identified an inception cohort of patients who were started on HD in January 1990
      from data collected by the United States Renal Data System (USRDS). Kaplan-Meier
      survival analyses were performed in these patients using the time at risk from 1
      January 1990 through 31 December 2010, the last date of the USRDS data collection
      period in this dataset. Cox proportional hazard models were used to assess
      mortality, adjusted for age at dialysis initiation. Subjects were censored at
      transplantation or end of follow-up. RESULTS: There were 1580 patients with ESRD
      secondary to SLE, 252 pediatric patients (62% African American) and 1328 adults
      (56% African American). African American pediatric patients with ESRD secondary
      to SLE had a 2-fold increased risk of death compared with African American
      children with other causes of ESRD [hazard ratio (HR): 2.1, 95% confidence
      interval (CI): 1.4-2.9, P < 0.01]. Increased risk of death was also seen in
      African American adults with ESRD secondary to SLE compared with both Caucasians
      with ESRD secondary to SLE (HR: 2.3, 95% CI: 1.2-4.2, P < 0.01) and African
      American adults with ESRD secondary to other diseases (HR: 1.2, 95% CI: 1.1-1.4,
      P < 0.01). CONCLUSION: Our study suggests that there is a significant increased
      risk for mortality in African American children and adults with ESRD secondary to
      SLE. This suggests that African Americans with ESRD secondary to SLE need
      aggressive monitoring.

PMID- 25859349
TI  - Anti-neutrophil cytoplasmic antibody-associated vasculitis associated with
      infectious mononucleosis due to primary Epstein-Barr virus infection: report of
      three cases.
AB  - Although the aetiology of anti-neutrophil cytoplasmic antibody (ANCA)-associated
      vasculitis remains unclear, it is generally believed that environmental factors
      such as infections contribute to its development of ANCA-associated vasculitis.
      Prior Epstein-Barr virus (EBV) infection is reported to be a trigger of systemic
      vasculitis. We herein report three cases of ANCA-associated vasculitis presenting
      with infectious mononucleosis due to primary EBV infection. The causal link
      between the two pathologies could not be proved, but primary EBV infection may
      play a role in the initiation or exacerbation of ANCA-associated vasculitis.
      Future studies are necessary to determine the interaction between these diseases
      conditions. 

PMID- 25859350
TI  - Life-threatening hyperkalemia in a patient with normal renal function.
AB  - With media focus on benefits from reducing sodium intake, there is increased
      popularity of salt substitutes, typically potassium chloride. While viewed by the
      public as a healthy alternative to standard table salt, less appreciated is the
      severe risk with certain comorbidities and medications. We report the case of an
      elderly female with chronically high salt substitute intake, normal renal
      function, diabetes, hypertension treated with angiotensin-converting enzyme
      inhibitor and beta blockade, who developed life-threatening hyperkalemia after a
      minimally invasive outpatient procedure. We describe the pathophysiology of the
      disruption in potassium homeostasis and emphasize the importance of dietary
      history and educating high-risk patients to avoid salt substitutes. 

PMID- 25859351
TI  - Rituximab for the treatment of refractory simultaneous anti-glomerular basement
      membrane (anti-GBM) and membranous nephropathy.
AB  - Antibody-mediated anti-glomerular basement membrane (anti-GBM) disease occurs
      rarely in the presence of another B-cell disorder, membranous nephropathy. The
      coexistence of these two autoimmune disorders would be anticipated to require
      differing, specific therapies targeted to each disease process. We describe a
      case of concomitant membranous nephropathy and anti-GBM disease in which
      conventional therapy, including steroids, plasmapheresis and cyclophosphamide,
      failed to attenuate the anti-GBM disease, yet responded to an alternative
      treatment of rituximab. This B-cell directed, monoclonal, chimeric antibody
      treatment substantially reduced anti-GBM antibody titers and led to
      discontinuation of plasmapheresis, while maintaining the remission of membranous
      nephropathy and anti-GBM disease. 

PMID- 25859352
TI  - Dialysis for twins.
AB  - A 32-year-old woman with known stage-4 chronic kidney disease due to lupus
      nephritis presented with twin pregnancy after in vitro fertilization at a
      gestational age of 24 weeks + 3 days because of imminent preterm labour. Repeated
      ultrasound evaluations confirmed intrauterine growth restriction in both twins
      and polyhydramnios as the cause of imminent preterm labour. After initiation of
      haemodialysis treatment, ultrasound evaluation showed a significant decrease in
      amniotic fluids, and also reduction in blood urea nitrogen and in clinical
      complaints could be observed. At a gestational age of 28 weeks + 4 days, delivery
      was performed by Caesarean section. This case study shows that effective
      treatment of elevated uraemic toxins significantly reduced the morbidity risks of
      the twins. 

PMID- 25859353
TI  - Overlap between dermatomyositis and ANCA vasculitides.
AB  - We present the second report of the association between antineutrophil cytoplasm
      antibodies (ANCA)-associated vasculitis with dermatomyositis (DM). A 47-year-old
      woman suddenly developed rapidly progressive renal failure in the context of
      (DM). The kidney biopsy showed focal and segmental necrotizing glomerulonephritis
      with crescent formation. Cyclophosphamide treatment was commenced resulting in a
      significant recovery of kidney function and maintenance of recovery at 6 months.
      Although the pathophysiology is unknown, we hypothesize that CD8-T-deficient
      cells and MPO+ neutrophils in the DM lesions play an important role in the
      disease process. 

PMID- 25859354
TI  - Renal phospholipidosis possibly induced by ranolazine.
AB  - A 76-year-old male Caucasian patient was treated in our hospital for acutely
      decompensated heart failure due to restrictive cardiomyopathy. Acute-on-chronic
      kidney failure developed with serum creatinine rising from 160 to 345 MUmol/L
      (1.8-3.9 mg/dL); therefore, a kidney biopsy was performed. Besides secondary
      focal-segmental glomerulosclerosis and minimal amyloidosis, histological analysis
      showed zebra bodies in the cytoplasm of some podocytes, suggesting renal
      phospholipidosis (PL). Possible causes for this storage disorder encompass
      Fabry's disease, in rare cases silicosis, and an iatrogenic drug-induced
      aetiology. The main suspects are cationic amphiphilic drugs, such as amiodarone
      and chloroquine. The only cationic amphiphilic drug our patient had taken was the
      anti-anginal ranolazine, a compound not yet associated with PL. The patient had
      taken ranolazine for diastolic dysfunction over a period of 9 months until 6
      weeks before renal biopsy. In the absence of a hereditary disorder, silicosis and
      well-known pharmaceutical triggers, a causative role of ranolazine seems likely,
      and this drug should be considered in the differential diagnosis of drug-induced
      PL. 

PMID- 25859355
TI  - Severe acute tubular necrosis observed subsequent to oxaliplatin administration.
AB  - A 67-year-old man known for metastatic colon cancer received treatment with
      oxaliplatin and developed severe acute kidney injury requiring dialysis. Renal
      biopsy revealed severe acute tubular necrosis. Acute kidney injury is a rare but
      severe adverse effect of oxaliplatin administration. 

PMID- 25859356
TI  - A rare cause of chylous ascites.
AB  - We report a patient with end-stage renal disease status after two renal
      transplantations. Milky-like ascites was noted since the immunosuppressant agent
      was switched to sirolimus (1 mg/day). Chylous ascites was diagnosed owing to the
      triglyceride of dialysate to serum being 15.98:15.99. Series studies were all
      negative. It is highly suspected that the cause of chylous ascites is sirolimus
      related because surgically related lymph vessel injury happens most often 6
      months after transplantation. Sirolimus-related chylous ascites is a rare cause
      of chylous ascites but the incidence rate increases after transplantation. Side
      effects of sirolimus include hyperlipidemia, anemia, thrombocytopenia,
      hepatotoxicity, delayed wound healing and a high rate of lymphoceles, lymph
      edema, and pulmonary alveolar proteinosis. Chylous ascitis has improved since the
      switch from sirolimus to other immunosuppressant agents. 

PMID- 25859357
TI  - Low-dose liquorice ingestion resulting in severe hypokalaemic paraparesis,
      rhabdomyolysis and nephrogenic diabetes insipidus.

PMID- 25859358
TI  - Acute kidney injury in a 'well-filled patient': an unusual cause of elevated
      jugular venous pressure.

PMID- 25859359
TI  - Renal allograft pyelonephritis and fungemia due to Candida krusei.

PMID- 25859360
TI  - Renal amyloidosis in cystic fibrosis: role of colchicine therapy.

PMID- 25859361
TI  - Oral galactose in children with focal and segmental glomerulosclerosis: a novel
      adjunct therapy.

PMID- 25859362
TI  - Plasma exchange for concurrent lupus nephritis and antiphospholipid syndrome.

PMID- 25859363
TI  - Anti-glomerular basement membrane glomerulonephritis after radiotherapy for early
      prostate cancer.

PMID- 25859364
TI  - A farewell editorial from the Clinical Kidney Journal's former Editor-in-Chief.

PMID- 25859365
TI  - Clinical manifestation of macrolide antibiotic toxicity in CKD and dialysis
      patients.
AB  - Macrolide antibiotics, erythromycin, clarithromycin and azithromycin are commonly
      prescribed for upper respiratory infection, and their use has recently been
      further linked to immunomodulatory effects. With the widespread and expanded use
      of macrolides, special attention should be paid to their potential adverse
      effects. We reported two cases of end-stage renal disease (ESRD) patients who
      developed hallucinations such as vivid images of worms after taking
      clarithromycin. Similar to previous case reports of clarithromycin neurotoxicity,
      the visual hallucination resolved upon cessation of clarithromycin. Furthermore,
      we discussed the pharmacokinetic properties and other toxicities of macrolide
      antibiotics in patients with chronic kidney disease and ESRD. 

PMID- 25859367
TI  - CKD hotspots around the world: announcement.

PMID- 25859366
TI  - Cocaine and kidney injury: a kaleidoscope of pathology.
AB  - Cocaine is abused worldwide as a recreational drug. It is a potent activator of
      the sympathetic nervous system leading to intense vasoconstriction, endothelial
      dysfunction, oxidative stress, platelet activation and decrease in prostaglandins
      E2 and prostacyclin. Cocaine can lead to widespread systemic adverse effects such
      as stroke, myocardial infarction, arterial dissection, vascular thrombosis and
      rhabdomyolysis. In human and rat kidneys, cocaine has been associated with
      glomerular, tubular, vascular and interstitial injury. It is not uncommon to
      diagnose cocaine-related acute kidney injury (AKI), malignant hypertension and
      chronic kidney disease. Cocaine abuse can lead to AKI by rhabdomyolysis,
      vasculitis, infarction, thrombotic microangiopathy and malignant hypertension. It
      is reported that 50-60% of people who use both cocaine and heroin are at
      increased risk of HIV, hepatitis and additional risk factors that can cause
      kidney diseases. While acute interstitial nephritis (AIN) is a known cause of
      AKI, an association of AIN with cocaine is unusual and seldom reported. We
      describe a patient with diabetes mellitus, hypertension and chronic hepatitis C,
      who presented with AKI. Urine toxicology was positive for cocaine and a kidney
      biopsy was consistent with AIN. Illicit drugs such as cocaine or contaminants may
      have caused AIN in this case and should be considered in the differential
      diagnosis of causes of AKI in a patient with substance abuse. We review the many
      ways that cocaine adversely impacts on kidney function. 

PMID- 25859368
TI  - CKD hotspots around the world: where, why and what the lessons are. A CKJ review
      series.
AB  - Chronic kidney disease (CKD) is one of the three causes of death that has had the
      highest increase in the last 20 years. The increasing CKD burden occurs in the
      context of lack of access of most of the world population to adequate healthcare
      and an incomplete understanding of the pathogenesis of CKD. However, CKD is not
      homogeneously distributed. CKD hotspots are defined as countries, region,
      communities or ethnicities with higher than average incidence of CKD. Analysis of
      CKD hotspots has the potential to provide valuable insights into the pathogenesis
      of kidney disease and to improve the life expectancy of the affected communities.
      Examples include ethnicities such as African Americans in the USA or Aboriginals
      in Australia, regions such as certain Balkan valleys or Central America and even
      groups of people sharing common activities or interests such as young women
      trying to lose weight in Belgium. The study of these CKD hotspots has identified
      underlying genetic factors, such as ApoL1 gene variants, environmental toxins,
      such as aristolochic acid and socioeconomic factors leading to nutritional
      deprivation and inflammation/infection. The CKD hotspots series of CKJ reviews
      will explore the epidemiology and causes in CKD hotspots, beginning with
      Australian Aboriginals in this issue. An online map of CKD hotspots around the
      world will feature the reviewed hotspots, highlighting known or suspected causes
      as well as ongoing projects to unravel the cause and providing a directory of
      public health officials, physicians and basic scientists involved in these
      efforts. Since the high prevalence of CKD in a particular region or population
      may only be known to local physicians, we encourage readers to propose further
      CKD hotspots to be reviewed. 

PMID- 25859369
TI  - The need for improved uptake of the KDIGO glomerulonephritis guidelines into
      clinical practice in Canada: a survey of nephrologists.
AB  - BACKGROUND: The lack of glomerulonephritis (GN) guidelines has historically
      contributed to substantial variability in the treatment of GN. We hypothesize
      that there are barriers to GN guideline implementation leading to incomplete
      translation of the 2012 KDIGO GN guidelines into patient care, and that current
      practice patterns deviate from guideline recommendations. METHODS: Adult
      nephrologists in Canada (N = 390) were surveyed using a web-based tool. The
      survey of 40 questions captured physician demographics, self-reported GN case
      load, treatment approaches and barriers to guideline implementation. RESULTS: The
      response rate was 44%. Physicians report seeing six (IQR 4,10) new cases of
      idiopathic GN every 6 months. The majority treat ANCA GN according to guidelines,
      but 9-37% treat nephrotic focal segmental glomerulosclerosis or membranous
      nephropathy with non-recommended immunosuppression and 6-9% do not treat with any
      immunotherapy, whereas 26% treat subnephrotic disease with immunosuppression. The
      majority indicated that standardized care tools would improve patient care, but
      they were only available to 25-44%. Patient education tools and nursing support
      are unavailable to 87 and 67%, respectively; insurance coverage for immune
      therapies is poorly accessible to 84%, yet 86% feel this would improve care and
      96% of physicians support comparing their practice with benchmarks from
      provincial GN registries. CONCLUSIONS: We show that 2 years after the publication
      of the KDIGO GN guidelines, 15-46% of Canadian nephrologists report treatment
      strategies not in keeping with guideline recommendations. We identify barriers to
      guideline implementation and widespread physician support for initiatives that
      address these barriers to improve patient care.

PMID- 25859370
TI  - Incidence of acute kidney injury following total joint arthroplasty: a
      retrospective review by RIFLE criteria.
AB  - BACKGROUND: Total joint arthroplasty (TJA) is a common procedure with demand for
      arthroplasties expected to increase exponentially. Incidence of acute kidney
      injury (AKI) following TJA is reportedly low, with most studies finding an
      incidence of <2%, increasing to 9% when emergency orthopaedic patients are
      included. METHODS: Retrospective medical record review of consecutive primary,
      elective TJA procedures was undertaken at a large tertiary hospital (Alfred).
      Demographic, peri-operative and post-operative data were recorded. Factors
      associated with AKI (based on RIFLE criteria) were determined using multiple
      logistic regression. RESULTS: Between January 2011 and June 2013, 425 patients
      underwent TJA; 252 total knee replacements (TKR) and 173 total hip replacements
      (THR). Sixty-seven patients (14.8%) developed AKI, including 51 TKR. Factors
      associated with AKI (adjusting for known confounders) include increasing body
      mass index [adjusted odds ratio (AOR) 1.14; 95% CI: 1.07, 1.21], older age (AOR
      1.07; 95% CI 1.02, 1.13) and lower pre-operative glomerular filtration rate (AOR
      0.97; 95% CI 0.96, 0.99) and taking angiotensin-converting enzyme inhibitors (AOR
      2.70; 95% CI 1.12, 6.48) and angiotensin-II receptor blockers (AOR 2.64; 95% CI
      1.18, 5.93). In most patients, AKI resolved by discharge, however, only 62% of
      patients had renal function tests after discharge. CONCLUSIONS: This study showed
      a rate of AKI of nearly 15% in our TJA population, substantially higher than
      previously reported. Given that AKI and long-term complications are associated,
      prospective research is needed to further understand the associated factors and
      predict those at risk of AKI. There may be opportunities to maximize the pre
      operative medical management and mitigate risk.

PMID- 25859371
TI  - Inpatient hemodialysis without anticoagulation in adults.
AB  - BACKGROUND: Anticoagulation use during hemodialysis (HD) is standard practice but
      issues related to an increased risk of hemorrhage associated with inpatients make
      this a concern. METHODS: An anticoagulation-free protocol in which (i) the
      dialysis circuit is aggressively primed with normal saline (NS) in an attempt to
      flush it of all air, (ii) blood flow during the HD treatment is maximized to up
      to 400 mL/min, (iii) the dialysis circuit is flushed every 15 min with 100 mL of
      NS, and (iv) the use of bloodlines that lack a blood-air interface was developed
      and used for all adult inpatient HD treatments at Rush University Medical Center.
      The purpose of this study was to evaluate the rate of HD circuit clotting using
      this approach and to determine if factors such as access type, blood flow,
      arterial and venous bloodline pressures, the need for reversing the arterial and
      venous access lines for low blood flow or high venous or arterial bloodline
      pressures, or the amount of net ultrafiltration were associated with HD circuit
      clotting. Patients were excluded from analysis if they were on a heparin drip,
      clopidogrel, warfarin or direct thrombin inhibitors. We reviewed 400 HD
      treatments in 400 adult patients from 12/12 to 10/13. RESULTS: The HD access in
      these patients consisted of catheters in 45%, native AV fistulas in 40% and
      grafts in 15% of the patients. The average blood flow in the treatments was 378
      +/- 46 mL/min. In 5% of the treatments, the arterial and venous bloodlines were
      reversed. Only 4 of the 400 (1%) of the treatments clotted the dialysis circuit.
      Factors associated with clotting were lower achieved blood flows (225 +/- 50
      mL/min versus 379 +/- 44 mL/min), higher arterial bloodline pressures (-198 +/-
      24 mmHg versus -151 +/- 45 mmHg) and reversal of arterial and venous access
      lines. CONCLUSION: Our anticoagulation-free protocol allows inpatient HD to be
      performed in adults across all access types and with essentially no circuit
      clotting.

PMID- 25859372
TI  - Medication burden in CKD-5D: impact of dialysis modality and setting.
AB  - BACKGROUND: Medication adherence is thought to be around 50% in the general and
      dialysis population. Reducing the pill burden (PB) reduces regime complexity and
      can improve adherence. Increased adherence should lead to improvement in
      treatment outcomes and patient quality of life. There is currently little
      published data on PB in CKD-5D across dialysis modalities. METHODS: This is a
      retrospective, single renal network study. All in-centre HD (MHD), peritoneal
      dialysis (PD) and home HD (HHD) patients were identified in the Greater
      Manchester East sector renal network. Information collected included age, sex,
      comorbidities, daily PB, dialysis vintage and adequacy. Data were retrieved from
      a customized renal database, clinic and discharge letters with cross validation
      from the general practitioner when needed. RESULTS: Two hundred and thirty-six
      prevalent dialysis patients were studied. HHD patients had a significantly lower
      PB (11 +/- 7 pills/day) compared with PD and MHD (16 +/- 7 pills/day). The HHD
      patients required fewer BP medications to meet the recommended target. HD setting
      was the only significant factor for reducing PB. For home therapies (HHD versus
      PD), weekly Kt/v and serum phosphate were significant factors influencing PB.
      When comparing all modalities, OR of PB >= 15/day for MHD versus HHD was 3.9 and
      PD versus HHD was 4.9. The influence of HHD is dominant above factors such as
      comorbidities or clinical variables in reducing PB for MHD. Higher clearances
      achieved by HHD could explain differences in PB with PD. CONCLUSION: This is the
      first comparative study of PB across all dialysis modalities and factors that
      influence it. The PB advantage in HHD may result in greater adherence and might
      contribute to the outcome benefit often seen with this modality. Higher
      clearances achieved by HHD could explain differences in PB with PD but the
      precise reasons for lower PB remain speculative and deserve further research in
      larger settings.

PMID- 25859373
TI  - Randomized trial of enteric-coated mycophenolate sodium versus mycophenolate
      mofetil in multi-system autoimmune disease.
AB  - BACKGROUND: The use of mycophenolate mofetil (MMF) in autoimmune disease is often
      limited by adverse effects. In this single-centre, open label, parallel design
      study, we investigated whether enteric-coated mycophenolate sodium (MS) is better
      tolerated and therefore more efficacious than MMF in primary systemic vasculitis
      (PSV) and systemic lupus erythematosus (SLE). METHODS: Forty patients with
      vasculitis or systemic lupus erythematosus (SLE) due to commence MMF for active
      disease or remission maintenance were randomized to receive either 1440 mg/day MS
      or 2000 mg/day MMF (18 PSV, 2 SLE per group) in addition to corticosteroids.
      Random allocation was performed by minimization for age, diagnosis and renal
      function using a computer algorithm. Twenty-five were treated for active disease
      (5 first-line therapy, 20 salvage therapy) and 15 for remission maintenance. The
      composite primary end point was treatment failure and/or drug intolerance over 12
      months. Treatment failure was defined as failure to achieve remission by 6 months
      or disease relapse and treatment intolerance was defined as inability to tolerate
      and maintain the target dose of MS or MMF within 12 months. RESULTS: Forty
      patients were included in the analyses. MS was associated with a lower primary
      end point rate [hazard ratio (HR) 0.37; 95% CI 0.17-0.80; P = 0.012] (11/20, 55%
      patients) compared with MMF (17/20, 85% patients). Treatment failure alone was
      less common in the MS group (HR 0.28; 95% CI 0.095-0.82; P = 0.020), although
      drug intolerance did not differ between groups (HR 0.53; 95% CI 0.20-1.42; P =
      0.21). Despite randomization, patients in the MMF group may have had a higher
      baseline risk for treatment failure; more MMF patients had refractory disease and
      granulomatosis with polyangiitis (Wegener's). A glomerular filtration rate (GFR)
      <=40 mL/min was associated with intolerance. Serious adverse events were common
      (55% MMF and 45% MS patients). CONCLUSIONS: No differences in treatment tolerance
      were observed between the MS and MMF groups. Despite similar treatment
      intolerance, MS was associated with improved efficacy in PSV and SLE compared
      with MMF. However, baseline group imbalances in factors potentially affecting
      remission and relapse may have influenced the results. Treatment intolerance was
      common and strongly associated with low GFR. Further treatment trials are
      warranted to investigate the effect of GFR on mycophenolic acid pharmacokinetics
      and clinical outcomes (ISRCTN83027184; EUDRACT 2005-002207-16; Funding Novartis
      UK).

PMID- 25859374
TI  - Capillary rarefaction: an early marker of microvascular disease in young
      hemodialysis patients.
AB  - BACKGROUND: Pediatric patients with chronic kidney disease (CKD) are at increased
      risk of early cardiovascular disease and premature death. Abnormalities in
      microvascular structure and function may presage end-organ damage including
      vascular calcification and myocardial ischemia associated with disordered mineral
      metabolism. Early detection of microvascular rarefaction (reduced density of
      capillaries) may identify at-risk patients and prompt timely therapeutic
      interventions. Our objective was to study capillary rarefaction in pediatric
      hemodialysis (HD) patients and to determine possible associations with mineral
      metabolism and cardiac risk biomarkers. METHODS: Capillary density (CD) was
      measured by nailfold capillaroscopy in 19 pediatric HD patients and 20 healthy
      controls. Demographic and biochemical markers were collected at entry and 6-month
      follow-up. RESULTS: CD was significantly decreased in HD patients compared with
      controls with a deficit of 24 and 31% at baseline and subsequent follow-up.
      Maximal CD correlated significantly with intact parathyroid hormone (iPTH) (r = 
      0.45; P = 0.005), serum calcium (r = -0.38; P = 0.02) and 25(OH) vitamin D levels
      (r = +0.36; P = 0.03) in HD patients. Capillary functional measures were similar
      to controls. By multivariate analysis, the primary negative determinants of CD
      were African American race and hyperparathyroidism; whereas, glomerular disease
      had a positive influence on capillary rarefaction (R (2) = 64.2% variance; P =
      0.001). CONCLUSION: Pediatric HD patients demonstrate a 'structural deficit' in
      CD but show preserved 'functional integrity'. Capillary rarefaction, an early
      risk factor of incipient vascular calcification, was strongly associated with
      biomarkers of altered mineral metabolism. Further studies are warranted to
      determine the impact of optimizing blood pressure and metabolic control on
      changes in capillary rarefaction in young CKD patients.

PMID- 25859375
TI  - The Choice of Renal Replacement Therapy (CORETH) project: study design and
      methods.
AB  - BACKGROUND: To date, research has neglected the patient's psychosocial and
      cognitive conditions as contributing factors to dialysis modality decision
      making. Hence, the Choice of Renal Replacement Therapy (CORETH) study aims to
      examine these conditions with regard to their impact on the choice. Here we
      describe the design of the multicentre study, which is supported by a grant from
      the German Ministry for Education and Research. METHODS: Two groups of patients
      will be compared after having chosen peritoneal or haemodialysis as permanent
      treatment. About 1200 participants from 50 dialysis centres all over Germany will
      be questioned. The questionnaire addresses social, psychological and shared
      decision-making aspects. Furthermore, cognitive functioning will be tested. For
      an economic evaluation direct and indirect costs of treatment will be calculated.
      Changes will be examined through a one-year follow-up. CONCLUSIONS: The results
      will enlighten the treatment choice under the German healthcare system. They will
      provide further insight regarding the discussion on patient autonomy. From the
      patients' perspective, the results will help to strengthen their participation in
      the individual process of health-related decision-making.

PMID- 25859376
TI  - Peritoneal dialysis in an extremely low-birth-weight infant with acute kidney
      injury.
AB  - Critically ill neonates are at high risk for acute kidney injury (AKI). Renal
      supportive therapy (RST) can be an important tool for supporting critically ill
      neonates with AKI, particularly in cases of oliguria and fluid overload. There
      are few reports of RST for management of oligo-anuric AKI in the extremely low
      birth-weight infant weighing <1000 g. We report successful provision of
      peritoneal dialysis (PD) to an 830-g neonate with oligo-anuric AKI through
      adaptation of a standard pediatric acute PD catheter. 

PMID- 25859377
TI  - Methotrexate toxicity treated with continuous venovenous hemofiltration,
      leucovorin and glucarpidase.
AB  - High-dose methotrexate (MTX) can produce acute kidney injury, impairing MTX
      elimination. Continuous venovenous hemofiltration (CVVH) may enhance elimination
      in this setting, although its use is largely unstudied. A 79-year-old man
      received IV MTX for central nervous system lymphoma, and over a 34-h period his
      serum creatinine increased from 1.09 to 2.24 mg/dL. His serum MTX concentration
      (sMTX) at the end of this time period was 59.05 umol/L. After urinary
      alkalinization and leucovorin and glucarpidase (CPDG2) treatment, sMTX decreased.
      Fluid overload ensued and CVVH was initiated. The initial MTX extraction ratio
      and clearance were 0.22 and 47.0 mL/min, respectively. No MTX extraction occurred
      at an sMTX of 0.15 umol/L. Continuous venovenous hemodialysis was initiated, and
      sMTX further declined. CVVH may help eliminate MTX and provide renal replacement
      at moderate sMTX. 

PMID- 25859378
TI  - Successful delivery of chemotherapy to treat small-cell prostate cancer in a
      patient undergoing haemodialysis.
AB  - We report on the successful treatment of small-cell prostate cancer in a patient
      undergoing haemodialysis. The therapeutic regimen included 300 mg/m(2) of
      carboplatin and 50 mg/m(2) of etoposide coupled with radical radiotherapy.
      Adjustments to the patient's haemodialysis prescription included the use of high
      flux, a larger dialyser surface area and an increased dialysis time. The
      parameters used aided tolerance to the drug, allowing the delivery of safe,
      effective treatment. At an interval of over 12 months post-treatment the patient
      shows no clinical evidence of recurrent disease. This case provides evidence to
      encourage the use of chemotherapy in otherwise potentially undertreated
      haemodialysed patients. 

PMID- 25859379
TI  - Urinary protein selectivity in nephrotic syndrome and pregnancy: resurrection of
      a biomarker when renal biopsy is contraindicated.
AB  - Significant proteinuria in pregnancy can indicate the presence of serious
      conditions requiring investigation and treatment. The nephrotic syndrome in
      pregnancy presents a multitude of difficulties and is a relative contraindication
      of renal biopsy, particularly in the third trimester. We present a case of
      nephrotic syndrome of unknown cause presenting at 33 weeks of pregnancy. With
      renal biopsy contraindicated, we used the urine protein selectivity test, a
      largely discarded test predicting steroid-responsive nephrotic syndrome, to help
      inform the decision to give steroids. This led to a successful clinical outcome
      including the avoidance of neonatal ICU care for baby. 

PMID- 25859380
TI  - Fanconi syndrome with lysinuric protein intolerance.
AB  - We present the case of a 9-year-old child with lysinuric protein intolerance and
      Fanconi syndrome. She was referred to our hospital with a persistent metabolic
      acidosis and polyuria. Renal investigations revealed all laboratory signs of
      Fanconi syndrome, with glucosuria, generalized aminoaciduria, phosphaturia and
      severe hypercalciuria. The diagnosis of Fanconi syndrome was confirmed by a renal
      biopsy that showed extensive lesions of proximal tubular epithelial cells with
      vacuolation of these cells and a sloughing of the brush border. 

PMID- 25859381
TI  - Desmopressin use prior to renal transplant biopsy-does it fit?
AB  - Desmopressin acetate (DDAVP), a selective agonist of type 2 vasopressin
      receptors, is sometimes used prior to percutaneous renal biopsy to reduce the
      risk of bleeding complications. DDAVP increases free water reabsorption in renal
      collecting ducts, potentially leading to water intoxication or dilutional
      hyponatraemia. We present two cases, where DDAVP was used prior to percutaneous
      renal transplant biopsy and was associated with severe hyponatraemia and
      neurological sequelae. With DDAVP being advocated in many centres prior to
      percutaneous renal biopsy, these cases highlight the need for increased awareness
      regarding side effects. In this report, we provide suggestions on strategies to
      minimize hyponatraemia in this context. 

PMID- 25859382
TI  - Warfarin-related nephropathy: possible role for the warfarin pharmacogenetic
      profile.
AB  - Warfarin-related nephropathy (WRN) is a renal complication of warfarin treatment
      associated with over-anticoagulation. We describe a case of a 73-year-old man
      affected by chronic kidney disease, essential hypertension and atrial
      fibrillation treated with warfarin. The patient presented a rapid course of
      kidney failure after many episodes of over-anticoagulation, and renal biopsy
      demonstrated WRN. Interestingly, the patient's warfarin pharmacogenetic profile
      showed that he was warfarin sensitive. This is the first report describing the
      presence of gene polymorphisms affecting warfarin metabolism in a subject with a
      biopsy-proven WRN. The patient was treated with corticosteroids obtaining a
      partial clinical response. 

PMID- 25859383
TI  - Imported bugs, not beasts: extensively drug-resistant tuberculosis and acute
      kidney injury.

PMID- 25859384
TI  - Black esophagus in the early kidney post-transplant period.

PMID- 25859385
TI  - Post-transplant diagnosis of hereditary leiomyomatosis and renal cell carcinoma
      syndrome in a kidney donor.

PMID- 25859387
TI  - The Research Registry - Answering the call to register every research study
      involving human participants.

PMID- 25859386
TI  - Laparoscopic colorectal surgery in learning curve: Role of implementation of a
      standardized technique and recovery protocol. A cohort study.
AB  - BACKGROUND: Despite the proven benefits, laparoscopic colorectal surgery is still
      under utilized among surgeons. A steep learning is one of the causes of its
      limited adoption. Aim of the study is to determine the feasibility and morbidity
      rate after laparoscopic colorectal surgery in a single institution, "learning
      curve" experience, implementing a well standardized operative technique and
      recovery protocol. METHODS: The first 50 patients treated laparoscopically were
      included. All the procedures were performed by a trainee surgeon, supervised by a
      consultant surgeon, according to the principle of complete mesocolic excision
      with central vascular ligation or TME. Patients underwent a fast track recovery
      programme. Recovery parameters, short-term outcomes, morbidity and mortality have
      been assessed. RESULTS: Type of resections: 20 left side resections, 8 right side
      resections, 14 low anterior resection/TME, 5 total colectomy and IRA, 3 total
      panproctocolectomy and pouch. Mean operative time: 227 min; mean number of lymph
      nodes: 18.7. Conversion rate: 8%. Mean time to flatus: 1.3 days; Mean time to
      solid stool: 2.3 days. Mean length of hospital stay: 7.2 days. Overall morbidity:
      24%; major morbidity (Dindo-Clavien III): 4%. No anastomotic leak, no mortality,
      no 30-days readmission. CONCLUSION: Proper laparoscopic colorectal surgery is
      safe and leads to excellent results in terms of recovery and short term outcomes,
      even in a learning curve setting. Key factors for better outcomes and shortening
      the learning curve seem to be the adoption of a standardized technique and
      training model along with the strict supervision of an expert colorectal surgeon.

PMID- 25859388
TI  - Erratum: Acquired immunity and asymptomatic reservoir impact on frontline and
      airport Ebola outbreak syndromic surveillance and response.
AB  - [This corrects the article DOI: 10.1186/2049-9957-3-41.]. 

PMID- 25859389
TI  - The ontogeny of naive and regulatory CD4(+) T-cell subsets during the first
      postnatal year: a cohort study.
AB  - As there is limited knowledge regarding the longitudinal development and early
      ontogeny of naive and regulatory CD4(+) T-cell subsets during the first postnatal
      year, we sought to evaluate the changes in proportion of naive (thymic and
      central) and regulatory (resting and activated) CD4(+) T-cell populations during
      the first postnatal year. Blood samples were collected and analyzed at birth, 6
      and 12 months of age from a population-derived sample of 130 infants. The
      proportion of naive and regulatory CD4(+) T-cell populations was determined by
      flow cytometry, and the thymic and central naive populations were sorted and
      their phenotype confirmed by relative expression of T cell-receptor excision
      circle DNA (TREC). At birth, the majority (94%) of CD4(+) T cells were naive
      (CD45RA(+)), and of these, ~80% had a thymic naive phenotype (CD31(+) and high
      TREC), with the remainder already central naive cells (CD31(-) and low TREC).
      During the first year of life, the naive CD4(+) T cells retained an overall
      thymic phenotype but decreased steadily. From birth to 6 months of age, the
      proportion of both resting naive T regulatory cells (rTreg;
      CD4(+)CD45RA(+)FoxP3(+)) and activated Treg (aTreg, CD4(+)CD45RA(-)FoxP3(high))
      increased markedly. The ratio of thymic to central naive CD4(+) T cells was lower
      in males throughout the first postnatal year indicating early sexual dimorphism
      in immune development. This longitudinal study defines proportions of CD4(+) T
      cell populations during the first year of postnatal life that provide a better
      understanding of normal immune development. 

PMID- 25859390
TI  - Adoptive T-cell immunotherapy for ganciclovir-resistant CMV disease after lung
      transplantation.
AB  - Infections with cytomegalovirus (CMV) can induce severe complications after solid
      organ transplantation (SOT). The prognosis for ganciclovir-resistant CMV
      infection and disease is particularly poor. Whereas adoptive transfer of CMV
      specific T cells has emerged as a powerful tool in hematopoietic stem cell
      transplant patients, its translation into the SOT setting remains a significant
      challenge as underlying immunosuppression inhibits the virus-specific T-cell
      response in vivo. Here, we demonstrate successful expansion and adoptive transfer
      of autologous CMV-specific T cells from a seronegative recipient of a
      seropositive lung allograft with ganciclovir-resistant CMV disease, resulting in
      the long-term reconstitution of protective anti-viral immunity, CMV infection,
      disease-free survival and no allograft rejection. 

PMID- 25859391
TI  - Primary hyperparathyroidism and Klinefelter's syndrome in a young man.
AB  - We report the association of primary hyperparathyroidism (PHPT) and Klinefelter's
      syndrome (KS) in a 22-year-old male complaining of worsening fatigue. PHPT was
      asymptomatic at the diagnosis, but the patient had worsening hypercalcemia and
      osteoporosis, and developed acute renal colic. He then underwent
      parathyroidectomy with resection of a single adenoma and normalization of calcium
      and parathyroid hormone levels. Clinical and therapeutic implications of this
      rare association are discussed. LEARNING POINTS: The coexistence of KS and PHPT
      is very uncommon.Patients with mild PHPT often have nonspecific symptoms that may
      be confused and superimposed with those of hypogonadism.KS patients, especially
      when young and already osteoporotic at diagnosis, should be screened for other
      causes of secondary osteoporosis, in particular PHPT.

PMID- 25859392
TI  - Biogas production experimental research using algae.
AB  - The current study is on the the use of macro-algae as feedstock for biogas
      production. Three types of macro-algae, Cladophora glomerata (CG), Chara fragilis
      (CF), and Spirogyra neglecta (SN), were chosen for this research. The
      experimental studies on biogas production were carried out with these algae in a
      batch bioreactor. In the bioreactor was maintained 35 +/- 1 degrees C
      temperature. The results showed that the most appropriate macro-algae for biogas
      production are Spirogyra neglecta (SN) and Cladophora glomerata (CG). The average
      amount of biogas obtained from the processing of SN - 0.23 m(3)/m(3)d, CG - 0.20
      m(3)/m(3)d, and CF - 0.12 m(3)/m(3)d. Considering the concentration of methane
      obtained during the processing of SN and CG, which after eight days and until the
      end of the experiment exceeded 60%, it can be claimed that biogas produced using
      these algae is valuable. When processing CF, the concentration of methane reached
      the level of 50% only by the final day of the experiment, which indicates that
      this alga is less suitable for biogas production. 

PMID- 25859393
TI  - Biodegradation of naphthalene using Pseudomonas aeruginosa by up flow anoxic
      aerobic continuous flow combined bioreactor.
AB  - BACKGROUND: Naphthalene is a poly aromatic hydrocarbon (PAH) present in many
      sediment-water systems. The aim of this study was to evaluate the applicability
      of an anoxic/aerobic system for the biological treatment of water polluted by
      naphthalene by Pseudomonas aeruginosa PTCC 1707 to utilize naphthalene. The
      naphthalene elimination from wastewater was determined in anoxic-aerobic
      continuous flow combined bioreactor under continuously oxic and anoxic
      conditions. Experiments were conducted in continues mode, and naphthalene was
      administered in consecutive spike doses. Then Pseudomonas aeruginosa bacteria
      suspension with a specific turbidity (0.5-10 NTU) was prepared from growing
      bacteria on R2A medium and injected to reactor. FINDINGS: At naphthalene
      concentration = 0.5-20 mg/L, 33-65.5% naphthalene removal efficiencies were
      observed. Mean COD removal efficiency in solid retention times of 2, 4, 6, and 8
      days was 82.7, 92.45, 95.97 and 96.1%, respectively. Naphthalene removal
      efficiency by bacterium pseudomonas at pH 8 was 96% and at pH 4, 5.5, 7 and 9.5,
      68, 80, 90 and 85%, respectively. As the initial concentration of naphthalene
      increased from 0.5 to 20 mg/L, the remaining concentration of naphthalene
      decreased from 33.4% to 65.5% after 3 days. CONCLUSION: Based on experimental
      results, it was determined that this process can effectively reduce naphthalene
      under optimal conditions and this method can be used for the removal of similar
      compounds.

PMID- 25859394
TI  - Antimicrobial Activity of Chemokine CXCL10 for Dermal and Oral Microorganisms.
AB  - CXCL10 (IP-10) is a small 10 kDa chemokine with antimicrobial activity. It is
      induced by IFN-gamma, chemoattracts mononuclear cells, and promotes adhesion of T
      cells. Recently, we detected CXCL10 on the surface of the skin and in the oral
      cavity. In the current study, we used broth microdilution and radial diffusion
      assays to show that CXCL10 inhibits the growth of Escherichia coli,
      Staphylococcus aureus, Corynebacterium jeikeium, Corynebacterium striatum, and
      Candida albicans HMV4C, but not Corynebacterium bovis, Streptococcus mutans,
      Streptococcus mitis, Streptococcus sanguinis, Fusobacterium nucleatum,
      Aggregatibacter actinomycetemcomitans, Poryphromonas gingivalis, or C. albicans
      ATCC 64124. The reason for the selective antimicrobial activity is not yet known.
      However, antimicrobial activity of CXCL10 may be related to its composition and
      structure, as a cationic 98 amino acid residue molecule with 10 lysine residues,
      7 arginine residues, a total net charge of +11, and a theoretical pI of 9.93.
      Modeling studies revealed that CXCL10 contains an alpha-helix at the N-terminal,
      three anti-parallel beta-strands in the middle, and an alpha-helix at the C
      terminal. Thus, CXCL10, when produced on the surface of the skin or in the oral
      cavity, likely has antimicrobial activity and may enhance innate antimicrobial
      and cellular responses to the presence of select commensal or opportunistic
      microorganisms. 

PMID- 25859395
TI  - How to compare treatment plans? Personalized perspective.

PMID- 25859396
TI  - miRNA - Therapeutic tool in breast cancer? Where are we now?
AB  - OBJECTIVE: The aim of this study was to review the current knowledge about
      involvement of microRNAs in breast cancer, and their potential in the clinic,
      published in scientific journals searched in Pubmed/Medline database until March
      2014. RESULTS: MicroRNAs (miRNAs) are a family of 21-25 nucleotide small RNAs
      molecules. Currently, it is well known that miRNA plays a key role in all
      cellular processes of the organism including tumour initiation and progression.
      Many studies have shown that circulating miRNAs are attractive, easily detectable
      tumour biomarkers. Breast cancer is one of the most common cancers in the world.
      It is clinically established that different subtypes may respond differently to
      therapies, give metastases and present drug resistance. MicroRNAs have a
      potential as diagnostic, prognostic and therapeutic tools in breast cancer.
      CONCLUSION: Molecular knowledge is crucial for choosing the most effective
      therapy for individual patients. MicroRNAs holds a great potential in anticancer
      therapy.

PMID- 25859397
TI  - Silk as an innovative biomaterial for cancer therapy.
AB  - Silk has been used for centuries in the textile industry and as surgical sutures.
      In addition to its unique mechanical properties, silk possesses other properties,
      such as biocompatibility, biodegradability and ability to self-assemble, which
      make it an interesting material for biomedical applications. Although silk forms
      only fibers in nature, synthetic techniques can be used to control the processing
      of silk into different morphologies, such as scaffolds, films, hydrogels,
      microcapsules, and micro- and nanospheres. Moreover, the biotechnological
      production of silk proteins broadens the potential applications of silk.
      Synthetic silk genes have been designed. Genetic engineering enables modification
      of silk properties or the construction of a hybrid silk. Bioengineered hybrid
      silks consist of a silk sequence that self-assembles into the desired
      morphological structure and the sequence of a polypeptide that confers a function
      to the silk biomaterial. The functional domains can comprise binding sites for
      receptors, enzymes, drugs, metals or sugars, among others. Here, we review the
      current status of potential applications of silk biomaterials in the field of
      oncology with a focus on the generation of implantable, injectable and targeted
      drug delivery systems and the three-dimensional cancer models based on silk
      scaffolds for cancer research. However, the systems described could be applied in
      many biomedical fields. 

PMID- 25859398
TI  - Integral dose: Comparison between four techniques for prostate radiotherapy.
AB  - AIM: Comparisons of integral dose delivered to the treatment planning volume and
      to the whole patient body during stereotactic, helical and intensity modulated
      radiotherapy of prostate. BACKGROUND: Multifield techniques produce large volumes
      of low dose inside the patient body. Delivered dose could be the result of the
      cytotoxic injuries of the cells even away from the treatment field. We calculated
      the total dose absorbed in the patient body for four radiotherapy techniques to
      investigate whether some methods have a potential to reduce the exposure to the
      patient. MATERIALS AND METHODS: We analyzed CyberKnife plans for 10 patients with
      localized prostate cancer. Five alternative plans for each patient were
      calculated with the VMAT, IMRT and TomoTherapy techniques. Alternative dose
      distributions were calculated to achieve the same coverage for PTV. Integral Dose
      formula was used to calculate the total dose delivered to the PTV and whole
      patient body. RESULTS: Analysis showed that the same amount of dose was deposited
      to the treated volume despite different methods of treatment delivery. The mean
      values of total dose delivered to the whole patient body differed significantly
      for each treatment technique. The highest integral dose in the patient's body was
      at the TomoTherapy and CyberKnife treatment session. VMAT was characterized by
      the lowest integral dose deposited in the patient body. CONCLUSIONS: The highest
      total dose absorbed in normal tissue was observed with the use of a robotic
      radiosurgery system and TomoTherapy. These results demonstrate that the exposure
      of healthy tissue is a dosimetric factor which differentiates the dose delivery
      methods.

PMID- 25859399
TI  - Influence of (11)C-choline PET/CT on radiotherapy planning in prostate cancer.
AB  - AIM: To evaluate the influence of (11)C-choline PET/CT on radiotherapy planning
      in prostate cancer patients. BACKGROUND: Precise information on the extension of
      prostate cancer is crucial for the choice of an appropriate therapeutic strategy.
      (11)C-choline positron emission tomography ((11)C-choline PET/CT) has two roles
      in radiation oncology (RT): (1) patient selection for treatment and (2) target
      volume selection and delineation. In conjunction with high-accuracy techniques,
      it might offer an opportunity of dose escalation and better tumour control while
      sparing healthy tissues. MATERIALS AND METHODS: We carried out a retrospective
      study in order to analyse RT planning modification based on (11)C-choline PET/CT
      in 16 prostate cancer patients. Patients were treated with hypofractionated step
      and-shoot Intensity Modulated Radiotherapy (IMRT), or Volumetric Modulated Arc
      Therapy (VMAT), and a daily cone-beam CT for Image Guided Radiation Therapy
      (IGRT). All patients underwent a (11)C-choline-PET/CT scan prior to radiotherapy.
      RESULTS: In 37.5% of cases, a re-delineation and new dose prescription occurred.
      Data show good preliminary clinical results in terms of biochemical control and
      toxicity. No gastrointestinal (GI)/genitourinary (GU) grade III toxicities were
      observed after a median follow-up of 9.5 months. CONCLUSIONS: In our experience,
      concerning the treatment of prostate cancer (PCa), (11)C-choline PET/CT may be
      helpful in radiotherapy planning, either for dose escalation or exclusion of
      selected sites.

PMID- 25859400
TI  - Postoperative radiotherapy in prostate cancer: Analysis of prognostic factors in
      a series of 282 patients.
AB  - AIM: To assess the outcomes of patients treated with postoperative RT in relation
      to the possible prognostic factors. BACKGROUND: Postoperative radiotherapy (RT)
      has been proved to reduce the risk of biochemical recurrence in high-risk
      prostate cancer patients. Baseline prostate specific antigen (PSA), pathological
      Gleason score (GS), positive surgical margins, nodal status and seminal vesicle
      invasion are independent predictors of biochemical relapse. MATERIALS AND
      METHODS: The clinical records of 282 patients who underwent postoperative RT were
      retrospectively reviewed. The prognostic value of postoperative PSA, preoperative
      risk class, nodal status, pathological GS, margins status, and administration of
      hormonal therapy (HT) was analyzed. RESULTS: Postoperative RT was delivered with
      a median dose to the prostatic fossa of 66 Gy (range 50-72) in 1.8-2 Gy/fraction.
      Median follow-up was 23.1 months (range 6-119). Five-year actuarial biochemical
      disease-free survival (bDFS) and overall survival rates were 76% and 95%,
      respectively. Higher bDFS was found for patients with postoperative PSA <0.02
      ng/ml (p = 0.03), low preoperative risk class (p = 0.01), pN0 (p = 0.003), GS 4-6
      (p = 0.0006), no androgen deprivation therapy (p = 0.02), and irrespective of
      surgical margin status (p = 0.10). Multivariate analysis showed that
      postoperative PSA and Gleason score had a significant impact on bDFS (p = 0.039
      and p = 0.05, respectively). CONCLUSIONS: Postoperative RT with a dose of 66 Gy
      offers an acceptable toxicity and an optimal disease control after radical
      prostatectomy in patients with different risk features. A postoperative PSA >0.02
      ng/ml could be considered as a prognostic factor and a tool to select patients at
      risk for progression.

PMID- 25859401
TI  - Radiochemotherapy in Anal Cancer: cCR, clinical outcomes and quality of life
      using two different treatment schedules.
AB  - AIM: Main endpoint was a response rate to therapy; secondary endpoints were
      disease-free survival, overall survival, acute and late toxicities, specially in
      terms of anorectal and urinary continence. BACKGROUND: Radiochemotherapy for anal
      cancer achieves a good clinical response, locoregional control, anal function
      preservation. However, oncologic outcomes can differ using radiotherapy plus
      fluorouracil and mytomicin vs. cisplatin and fluorouracil. METHODS: Between 2000
      and 2012, 27 anal cancer patients receiving radiotherapy combined with two
      different radiochemotherapy schedules, fluorouracil and mytomicin (group A) and
      cisplatin plus fluorouracil (group B). The Kaplan-Meier method was also used to
      estimate local control, overall survival and disease free survival. Statistical
      significance between curves was evaluated using the Log-rank test. RESULTS:
      Complete pathological response was found in 85.2% of patients, with higher rates
      of response in the group A (100% vs. 63.6%, p = 0.039). No significantly
      difference was found between the two groups for the other endpoints. Low rates of
      both acute and late toxicities were recorded. CONCLUSION: Radiotherapy plus
      fluorouracil and mytomicin provide a better complete pathological response than
      radiotherapy plus cisplatin and fluorouracil and a greater rate of anal sphincter
      function preservation. Globally, radiochemotherapy of the anal cancer provides
      excellent clinical outcomes with a good profile of acute and late toxicity,
      without difference between the two groups studied.

PMID- 25859402
TI  - Decentralisation of radiation therapy. Is it possible and beneficial to patients?
      Experience of the first 5 years of a satellite radiotherapy unit in the province
      of Tarragona, Spain.
AB  - BACKGROUND: The concept of satellite radiotherapy originates in countries whose
      populations are largely dispersed in order to treat homogenously the population
      by a unique fixed team. AIM: This report describes the creation and management of
      a satellite radiotherapy unit in Spain (RUTE-Radiotherapy Unit, Terres de
      l'Ebre). It is managed by the Radiation Oncology Department at Hospital
      Universitari Sant Joan de Reus. We report the benefit gained in the comfort of
      patients and the economic benefit gained by reducing the expense of transport for
      the health care system. MATERIALS AND METHODS: RUTE is equipped with a linear
      accelerator. A team of 10 physicians, specialised in different oncology
      pathologies, travel to RUTE on a rotational basis from the main Radiation
      Oncology Department. Simulation and planning of treatment is managed at the
      Radiation Oncology Department in Reus. Patients from RUTE only have to visit the
      centre in Reus once throughout the treatment process. RESULTS: Since August 2008,
      1500 patients have completed treatment in the satellite unit. The implementation
      of RUTE has greatly improved the comfort of patients and along with that, there
      have been important savings in transport costs to the regional health care
      system. CONCLUSIONS: Despite the high technological requirements of our
      speciality, decentralising radiotherapy is feasible. We can guarantee the highest
      standards of treatment with no differences from attending the main centre. It
      implies a clear benefit for the comfort of the patients and an economic benefit
      by decreasing transport costs.

PMID- 25859403
TI  - Oral administration of melatonin modulates the expression of tumor necrosis
      factor-alpha (TNF-alpha) gene in irradiated rat cervical spinal cord.
AB  - AIM: We aimed to determine the changes in TNF-alpha expression and
      Malondialdehyde (MDA) level in a short time after irradiation. Furthermore, we
      evaluated the effect of melatonin on the modulation of TNF-alpha gene expression.
      BACKGROUND: The radio-sensitivity of the cervical spinal cord limits the dose of
      radiation which can be delivered to tumors in the neck region. There is
      increasing evidence that TNF-alpha has a role in the development of the acute
      phase of spinal cord injury. MATERIALS/METHODS: Four groups of rats were
      investigated. Group 1 (vehicle treatment) served as the control. Group 2
      (radiation) was treated with the vehicle, and 30 min later, the rats were exposed
      to radiation. Group 3 (radiation + melatonin) was given an oral administration of
      melatonin (100 mg/kg body weight) and 30 min later exposed to radiation in the
      same manner as in group 2. Group 4 (melatonin-only) was also given an oral
      administration of melatonin (100 mg/kg body weight). 5 mg/kg of melatonin was
      administered daily to rats in groups 3 and 4, and the vehicle was administered
      daily to rats in groups 1 and 2. RESULTS: Three weeks after irradiation, TNF
      alpha gene up-regulated almost 5 fold in the irradiated group compared to the
      normal group. TNF-alpha gene expression in the melatonin pretreatment group,
      compared to the radiation group, was significantly down-regulated 3 weeks after
      irradiation (p < 0.05). MDA levels increased after irradiation and then
      significantly decreased under melatonin treatment. CONCLUSION: We suggest that
      inhibition of TNF-alpha expression by oral administration of melatonin may be a
      therapeutic option for preventing radiation-induced spinal cord injury.

PMID- 25859404
TI  - Is dose escalation achievable for esophageal carcinoma?
AB  - AIM: To investigate the feasibility of dose escalation using rapid arc (RA) and
      Helical Tomotherapy (HT) for patients with upper, middle and distal esophageal
      carcinomas, even for large tumor volumes. BACKGROUND: In esophageal cancer, for
      patients with exclusive radio-chemotherapy, local disease control remains poor.
      Planning study with dose escalation was done for two sophisticated modulated
      radiotherapy techniques: Rapid arc against Tomotherapy. MATERIALS AND METHODS:
      Six patients treated with a RA simultaneous integrated boost (SIB) of 60 Gy were
      re-planned for RA and HT techniques with a SIB dose escalated to 70 Gy. Dose
      volume histogram statistics, conformity indices and homogeneity indices were
      analyzed. For a given set of normal tissue constraints, the capability of each
      treatment modality to increase the GTV dose to 70 Gy was investigated. RESULTS:
      Either HT or VMAT may be used to escalate the dose delivered in esophageal tumors
      while maintaining the spinal cord, lung and heart doses within tolerance.
      Adequate target coverage was achieved by both techniques. Typically, HT achieved
      better lung sparing and PTV coverage than did RA. CONCLUSIONS: Dose escalation
      for esophageal cancer becomes clinically feasible with the use of RA and HT. This
      promising result could be explored in a carefully controlled clinical study which
      considered normal tissue complications and tumor control as endpoints.

PMID- 25859405
TI  - Prospective study on dosimetric comparison of helical tomotherapy and 3DCRT for
      craniospinal irradiation - A single institution experience.
AB  - AIM: This prospective study aims to assess feasibility of helical tomotherapy
      (HT) for craniospinal irradiation (CSI) and perform dosimetric comparison of
      treatment plans for both HT and 3D conformal radiotherapy (3DCRT). BACKGROUND:
      CSI is a challenging procedure. Large PTV size requires field matching due to
      technical limitations of standard linear accelerators, which cannot irradiate
      such volumes as a single field. HT could help to avoid these limitations as
      irradiation of long fields is possible without field matching. MATERIALS AND
      METHODS: Three adults were enrolled from 2009 to 2010. All patients received
      radiochemotherapy. Treatment plans in prone position for 3DCRT and in supine
      position for HT were generated. The superior plan was used for patients'
      irradiation. Plans were compared with the application of DVH, Dx parameters -
      where x represents a percentage of the structure volume receiving a normalized
      dose and homogeneity index (HI). RESULTS: All patients received HT irradiation.
      The treatment was well tolerated. The HT plans resulted in a better dose coverage
      and uniformity in the PTV: HI were 5.4, 7.8, 6.8 for HT vs. 10.3, 6.6, 10.4 for
      3DCRT. For most organs at risk (OARs), the D(V80) was higher for HT than for
      3DCRT, whereas D(V5) was lower for HT. CONCLUSIONS: HT is feasible for CSI, and
      in comparison with 3DCRT it improves PTV coverage. HT reduces high dose volumes
      of OARs, but larger volumes of normal tissue receive low radiation dose. HT
      requires further study to establish correlations between dosimetrical findings
      and clinical outcomes, especially with regard to late sequelae of treatment.

PMID- 25859406
TI  - HOTAIR: an oncogenic long non-coding RNA in different cancers.
AB  - Long non-coding RNAs (lncRNAs) refer to a group of RNAs that are usually more
      than 200 nucleotides and are not involved in protein generation. Instead, lncRNAs
      are involved in different regulatory processes, such as regulation of gene
      expression. Different lncRNAs exist throughout the genome. LncRNAs are also known
      for their roles in different human diseases such as cancer. HOTAIR is an lncRNA
      that plays a role as an oncogenic molecule in different cancer cells, such as
      breast, gastric, colorectal, and cervical cancer cells. Therefore, HOTAIR
      expression level is a potential biomarker for diagnostic and therapeutic purposes
      in several cancers. This RNA takes part in epigenetic regulation of genes and
      plays an important role in different cellular pathways by interacting with
      Polycomb Repressive Complex 2 (PRC2). In this review, we describe the molecular
      function and regulation of HOTAIR and its role in different types of cancers. 

PMID- 25859407
TI  - Critical protein GAPDH and its regulatory mechanisms in cancer cells.
AB  - Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), initially identified as a
      glycolytic enzyme and considered as a housekeeping gene, is widely used as an
      internal control in experiments on proteins, mRNA, and DNA. However, emerging
      evidence indicates that GAPDH is implicated in diverse functions independent of
      its role in energy metabolism; the expression status of GAPDH is also deregulated
      in various cancer cells. One of the most common effects of GAPDH is its
      inconsistent role in the determination of cancer cell fate. Furthermore, studies
      have described GAPDH as a regulator of cell death; other studies have suggested
      that GAPDH participates in tumor progression and serves as a new therapeutic
      target. However, related regulatory mechanisms of its numerous cellular functions
      and deregulated expression levels remain unclear. GAPDH is tightly regulated at
      transcriptional and posttranscriptional levels, which are involved in the
      regulation of diverse GAPDH functions. Several cancer-related factors, such as
      insulin, hypoxia inducible factor-1 (HIF-1), p53, nitric oxide (NO), and
      acetylated histone, not only modulate GAPDH gene expression but also affect
      protein functions via common pathways. Moreover, posttranslational modifications
      (PTMs) occurring in GAPDH in cancer cells result in new activities unrelated to
      the original glycolytic function of GAPDH. In this review, recent findings
      related to GAPDH transcriptional regulation and PTMs are summarized. Mechanisms
      and pathways involved in GAPDH regulation and its different roles in cancer cells
      are also described. 

PMID- 25859408
TI  - Biomarkers for enhancing the radiosensitivity of nasopharyngeal carcinoma.
AB  - Nasopharyngeal carcinoma (NPC) is a common head and neck malignancy. The
      incidence of NPC is higher in Southern China and Southeast Asia compared with
      Western countries. Given its high radiosensitivity, the standard treatment for
      NPC is radiotherapy. However, radioresistance remains a serious obstacle to
      successful treatment. Radioresistance can cause local recurrence and distant
      metastases in some patients after treatment by radiation. Thus, special emphasis
      has been given to the discovery of effective radiosensitizers. This review aims
      to discuss the biomarkers, classified according to the main mechanisms of
      radiosensitization, which can enhance the sensitivity of NPC cells to ionizing
      radiation. 

PMID- 25859409
TI  - Change of SPARC expression after chemotherapy in gastric cancer.
AB  - OBJECTIVE: The expression of tumor biomarkers may change after chemotherapy.
      However, whether secreted protein acidic and rich in cysteine (SPARC) expression
      changes after chemotherapy in gastric cancer (GC) is unclear. This study
      investigated the influence of chemotherapy on SPARC expression in GC. METHODS:
      Immunohistochemistry was used to analyze SPARC expression in 132 GC cases
      (including 54 cases with preoperative chemotherapy and 78 cases without
      preoperative chemotherapy). SPARC expression of postoperative specimens with and
      without preoperative chemotherapy was assessed to analyze the influence of
      chemotherapy on SPARC expression. RESULTS: SPARC was highly expressed in GC
      compared with the desmoplastic stroma surrounding tumor cells and noncancerous
      tissues. High SPARC expression was correlated with invasion depth, lymph node,
      and TNM stage. After chemotherapy, a lower proportion of high SPARC expression
      was observed in patients with preoperative chemotherapy than in the controls. For
      54 patients with preoperative chemotherapy, gross type, histology, depth of
      invasion, lymph node, TNM stage, and SPARC expression were related to overall
      survival. Further multivariate analysis showed that lymph node, histology, and
      SPARC expression after chemotherapy were independent prognostic factors.
      CONCLUSION: SPARC expression may change after chemotherapy in GC. SPARC
      expression should be reassessed for patients with GC after chemotherapy.

PMID- 25859410
TI  - Clinical features of AIDS patients with Hodgkin's lymphoma with isolated bone
      marrow involvement: report of 12 cases at a single institution.
AB  - OBJECTIVE: To study the main clinical and histopathological features of 12
      patients with Hodgkin's lymphoma (HL) diagnosed primarily from bone marrow (BM)
      involvement. METHODS: We included 12 acquired immunodeficiency syndrome (AIDS)
      patients with HL assisted in the F. J. Muniz Infectious Diseases Hospital since
      January 2002 to December 2013. The diagnosis of HL with primary BM involvement in
      patients was confirmed by clinical, histopathological, and immunohistochemical
      findings. RESULTS: All patients presented "B" symptoms and pancytopenia. All of
      them had stage IV neoplasm disease because of BM infiltration. The median of
      CD4(+) T-cell counts was 114 cells/MUL, and mixed cellularity (MC) was the most
      frequent histopathological subtype of 92% cases. CONCLUSION: When other causes
      are excluded, BM biopsy should be performed in AIDS patients with "B" symptoms
      and pancytopenia to evaluate BM infiltration by atypical lymphocytes.

PMID- 25859411
TI  - Clinicopathologic features of 112 cases with mantle cell lymphoma.
AB  - OBJECTIVE: This study aims to explore the clinicopathologic features of 112
      patients with mantle cell lymphoma (MCL). METHODS: Data from 112 MCL cases were
      collected, and immunohistochemical assay was conducted. Fluorescence in situ
      hybridization (FISH) detected a break in the CCND1 gene. The t-test was used in
      the statistical analysis. RESULTS: All tumor cells in the 112 cases expressed B
      cell-related antigen, including 1 blastoid subtype and 1 polymorphic subtype.
      Among all cases, 106 expressed CD5 and 104 expressed cyclin D1. A break in the
      CCND1 gene was not found in 3 cases with CD5-MCL. IgH/CCND1 polyploid was
      observed in 2 classic cases. CONCLUSION: MCL is a type of special
      immunophenotypic B-cell lymphoma. The prognoses of blastoid and polymorphic
      subtypes are poor. Special subtypes should be classified during diagnosis.

PMID- 25859412
TI  - Difference between papillary and follicular thyroid carcinoma outcomes: an
      experience from Egyptian institution.
AB  - OBJECTIVE: Differentiated thyroid carcinomas (DTCs) are classified into papillary
      thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC). DTCs are analyzed
      as a single group in clinical studies that investigated the prognostic factors
      and prognosis of these malignancies. However, the biological behaviors of these
      carcinomas significantly differ. In the present study, we aimed to detect
      differences in the outcomes between PTC and FTC in Mansoura University Hospital
      in Egypt. METHODS: A total of 558 patients with histologically proven thyroid
      carcinomas from January 2003 to December 2012 were retrospectively enrolled. The
      clinical and pathological data of patients were reviewed. RESULTS: Large primary
      tumor size, lymph node involvement, extrathyroid extension, and distant
      metastasis were significant poor prognostic factors for overall survival (OS) in
      old PTC patients. Cox hazard analysis showed that the patient's age, extra
      thyroid extension, and distant metastasis were the only independent prognostic
      factors. In FTC patients, only the distant metastasis and degree of tumor
      invasion were significant poor prognostic factors in OS univariate analysis.
      However, these factors were nonsignificant in multivariate analysis. The 10-year
      OS rates were 97% and 89% for PTC and FTC, respectively (P=0.003). The 10-year
      disease-free survival (DFS) rates were 77.2% in PTC vs. 65% in FTC (P=0.179).
      CONCLUSION: The significant prognostic factors vary between the two types of
      DTCs. Therefore, PTC and FTC patients need to be analyzed and reported
      independently. PTC survival is widely and significantly affected by age,
      extrathyroid extension, and distant metastasis. By contrast, these factors were
      nonsignificant in FTC, which showed poorer survival than PTC.

PMID- 25859413
TI  - Can palliative radiotherapy influence prostate-specific antigen response in
      patients with castrate-resistant prostate cancer treated with systemic therapy
      (chemotherapy or abiraterone)?-a report of three cases.
AB  - Palliative radiotherapy (pRT) is primarily employed for palliation of bone pain
      in patients with castrate-resistant prostate cancer (CRPC). However, evidence
      that pRT influences prostate-specific antigen response in patients with CRPC on
      systemic therapy is lacking. We describe three cases of CRPC progressing after
      treatment with docetaxel (n=2) and abiraterone (n=1), who responded unusually
      after pRT for bone pain with the development of a significant biochemical
      response and restoration of response to systemic therapy. The possibility of pRT
      influencing metastatic disease in CRPC has not been previously reported, and
      raises the possibility of radiation-induced modulation of anti-tumor immune
      response mechanisms that may play a role in the restoration of response to
      systemic treatment. 

PMID- 25859414
TI  - Eukaryotic cell encystation and cancer cell dormancy: is a greater devil veiled
      in the details of a lesser evil?
AB  - Cancer cell dormancy is the main cause of cancer recurrence and failure of
      therapy as dormant cells evade not only the anticancer drugs but also the host
      immune system. These dormant cells veil themselves from detection by imaging
      and/or using biomarkers, which imposes an additional problem in targeting such
      cells. A similar form of hibernation process known as encystation is studied in
      detail for pathogenic unicellular eukaryotic microorganisms. By examination using
      microarray gene expression profiles, immunocytochemistry tools, and siRNAs during
      the process of encystation, understanding the covert features of cancer cell
      dormancy as proposed could be possible. This knowledge can be extended to dormant
      cancer cells to uncover the mechanisms that underlie this ghost, yet dangerous
      state of human cancers. We propose a strategy to induce dormancy and exit this
      state by application of knowledge gained from the encystation induction and
      retrieval processes in pathogenic eukaryotic microorganisms. Given that early
      detection and characterization of dormant malignant tumor cells is important as a
      general strategy to monitor and prevent the development of overt metastatic
      disease, this homology may enable the design of therapies that could either awake
      the dormant cell from dormancy to make it available for therapies or prolong such
      a phase to make cancer appear as a chronic disease. 

PMID- 25859415
TI  - Highlights of Miami winter symposium 2015: into the era of immunotherapy.
AB  - Personalized cancer medicine has seen significant improvements over the past
      decade. Recent Elsevier conference: Miami winter symposium 2015 (MWS2015)
      "Towards Personalized Cancer Medicine" meeting was dedicated to this exciting
      field, and focused on new progress in personalized drug development and antibody
      drug against checkpoint pathway. This meeting report summarizes the key
      developments presented and discussed at the meeting, with a focus on
      immunotherapy, especially on the CTLA-4 and PD-1/PD-L1 pathways. The monoclonal
      antibody drugs intervening these checkpoint pathways have the potential to play a
      larger role in personalize medicine within the near future. Here we intended to
      provide a comprehensive summary about ongoing trends and future perspectives on
      personalized medicine in cancer therapy. 

PMID- 25859417
TI  - Sparse Bayesian Graphical Models for RPPA Time Course Data.
AB  - Advances in functional proteomic technologies have significantly enriched our
      knowledge of protein functions and their interactions in bio-molecular pathways.
      We discuss inference for RPPA (reverse phase protein array) data that measure the
      expression of the protein markers over time. We exploit the dynamical nature of
      the experiment to build a directed network of protein interactions. For this, we
      employ a Bayesian graphical model with an informative prior that favors sparsity.
      Conditional on the network, we model dependence at the level of latent binary
      indicators rather than the raw expression measurements. One of the key features
      of the proposed approach is a hierarchical model that allows for the dependence
      structure to be shared across different experiments, in the case of the
      motivating application across different drugs and doses. This is critical to
      facilitate meaningful inference with the limited available sample sizes. The
      second key feature is a sparsity inducing prior on the dependence structure. We
      show an application of the method to data measuring abundance of phosphorylated
      proteins in a human ovarian cell line.

PMID- 25859416
TI  - Echocardiographic detection of transpulmonary bubble transit during acute
      respiratory distress syndrome.
AB  - BACKGROUND: Transpulmonary bubble transit (TPBT) detected with contrast
      echocardiography is reported as a sign of intrapulmonary shunt during cirrhosis
      or exercise in healthy humans. However, its physiological meaning is not clear
      during acute respiratory distress syndrome (ARDS). Our aim was to determine the
      prevalence, significance, and prognosis of TPBT detection during ARDS. METHODS:
      This was a prospective observational study in an academic medical intensive care
      unit in France. Two hundred and sixteen consecutive patients with moderate-to
      severe ARDS underwent transesophageal echocardiography with modified gelatine
      contrast. Moderate-to-large TPBT was defined as right-to-left passage of at least
      ten bubbles through a pulmonary vein more than three cardiac cycles after
      complete opacification of the right atrium. Patients with intra-cardiac shunt
      through patent foramen ovale were excluded. RESULTS: The prevalence of moderate
      to-large TPBT was 26% (including 42 patients with moderate and 15 with large
      TPBT). Patients with moderate-to-large TPBT had higher values of cardiac index
      and heart rate as compared to those without TPBT. There was no significant
      difference in PaO2/FIO2 ratio between groups, and TPBT was not influenced by end
      expiratory positive pressure level in 93% of tested patients. Prevalence of
      septic shock was higher in the group with moderate-to-large TPBT. Patients with
      moderate-to-large TPBT had fewer ventilator-free days and intensive care unit
      free days within the first 28 days, and higher in-hospital mortality as compared
      to others. CONCLUSIONS: Moderate-to-large TPBT was detected with contrast
      echocardiography in 26% of patients with ARDS. This finding was associated with a
      hyperdynamic and septic state, but did not influence oxygenation.

PMID- 25859418
TI  - A Bayesian Graphical Model for Integrative Analysis of TCGA Data.
AB  - We integrate three TCGA data sets including measurements on matched DNA copy
      numbers (C), DNA methylation (M), and mRNA expression (E) over 500+ ovarian
      cancer samples. The integrative analysis is based on a Bayesian graphical model
      treating the three types of measurements as three vertices in a network. The
      graph is used as a convenient way to parameterize and display the dependence
      structure. Edges connecting vertices infer specific types of regulatory
      relationships. For example, an edge between M and E and a lack of edge between C
      and E implies methylation-controlled transcription, which is robust to copy
      number changes. In other words, the mRNA expression is sensitive to methylational
      variation but not copy number variation. We apply the graphical model to each of
      the genes in the TCGA data independently and provide a comprehensive list of
      inferred profiles. Examples are provided based on simulated data as well.

PMID- 25859419
TI  - MicroRNA biomarkers for early detection of embryonic malformations in pregnancy.
AB  - Congenital birth defects, manifested in newborn infants, are formed during early
      embryogenesis. Targeted and individualized interventions to prevent birth defects
      require early detection of risk and signs of developmental abnormalities. Current
      diagnosis of structural anomalies largely relies on ultrasonography, which can
      only detect abnormities after their formation in fetuses. Biomolecules, mainly
      proteins, in maternal blood have been used as indicators of fetal anomalies;
      however, they lack adequate sensitivity for detecting embryonic malformations.
      Recently, cell-free microRNAs (miRNAs) have been found in blood and evaluated as
      biomarkers for diseases. Expression of certain miRNAs in maternal plasma has been
      shown to be correlated with birth defects in infants. Although their reliability
      and sensitivity remain to be validated, miRNAs, which can be amplified and
      sequenced, are potentially sensitive and specific biomarkers for early embryonic
      dysmorphogenesis.

PMID- 25859420
TI  - Noise-induced precursors of state transitions in the stochastic Wilson-cowan
      model.
AB  - The Wilson-Cowan neural field equations describe the dynamical behavior of a 1-D
      continuum of excitatory and inhibitory cortical neural aggregates, using a pair
      of coupled integro-differential equations. Here we use bifurcation theory and
      small-noise linear stochastics to study the range of a phase transitions-sudden
      qualitative changes in the state of a dynamical system emerging from a
      bifurcation-accessible to the Wilson-Cowan network. Specifically, we examine
      saddle-node, Hopf, Turing, and Turing-Hopf instabilities. We introduce
      stochasticity by adding small-amplitude spatio-temporal white noise, and analyze
      the resulting subthreshold fluctuations using an Ornstein-Uhlenbeck
      linearization. This analysis predicts divergent changes in correlation and
      spectral characteristics of neural activity during close approach to bifurcation
      from below. We validate these theoretical predictions using numerical
      simulations. The results demonstrate the role of noise in the emergence of
      critically slowed precursors in both space and time, and suggest that these early
      warning signals are a universal feature of a neural system close to bifurcation.
      In particular, these precursor signals are likely to have neurobiological
      significance as early warnings of impending state change in the cortex. We
      support this claim with an analysis of the in vitro local field potentials
      recorded from slices of mouse-brain tissue. We show that in the period leading up
      to emergence of spontaneous seizure-like events, the mouse field potentials show
      a characteristic spectral focusing toward lower frequencies concomitant with a
      growth in fluctuation variance, consistent with critical slowing near a
      bifurcation point. This observation of biological criticality has clear
      implications regarding the feasibility of seizure prediction. 

PMID- 25859421
TI  - Monochromaticity of orientation maps in v1 implies minimum variance for
      hypercolumn size.
AB  - In the primary visual cortex of many mammals, the processing of sensory
      information involves recognizing stimuli orientations. The repartition of
      preferred orientations of neurons in some areas is remarkable: a repetitive, non
      periodic, layout. This repetitive pattern is understood to be fundamental for
      basic non-local aspects of vision, like the perception of contours, but important
      questions remain about its development and function. We focus here on Gaussian
      Random Fields, which provide a good description of the initial stage of
      orientation map development and, in spite of shortcomings we will recall, a
      computable framework for discussing general principles underlying the geometry of
      mature maps. We discuss the relationship between the notion of column spacing and
      the structure of correlation spectra; we prove formulas for the mean value and
      variance of column spacing, and we use numerical analysis of exact analytic
      formulae to study the variance. Referring to studies by Wolf, Geisel, Kaschube,
      Schnabel, and coworkers, we also show that spectral thinness is not an essential
      ingredient to obtain a pinwheel density of pi, whereas it appears as a signature
      of Euclidean symmetry. The minimum variance property associated to thin spectra
      could be useful for information processing, provide optimal modularity for V1
      hypercolumns, and be a first step toward a mathematical definition of
      hypercolumns. A measurement of this property in real maps is in principle
      possible, and comparison with the results in our paper could help establish the
      role of our minimum variance hypothesis in the development process. 

PMID- 25859422
TI  - Comparison of cake compositions, pepsin digestibility and amino acids
      concentration of proteins isolated from black mustard and yellow mustard cakes.
AB  - As a byproduct of oil production, black and yellow mustard cakes protein are
      considered as potential source of plant protein for feed applications to poultry,
      fish and swine industries. The protein contents in black and yellow mustard cakes
      were 38.17% and 28.80% and their pepsin digestibility was 80.33% and 77.43%,
      respectively. The proteins were extracted at different pH and maximum proteins
      (89.13% of 38.17% and 87.76% of 28.80% respectively) isolated from black and
      yellow mustard cakes at pH 12. The purity of isolated proteins of black and
      yellow mustard cakes was 89.83% and 91.12% respectively and their pepsin
      digestibility was 89.67% and 90.17% respectively which assigned the absence of
      antinutritional compounds. It was found that essential amino acids isoleucine,
      lysine, methionine, threonine and tryptophan and non essential amino acids
      arginine and tyrosine were present in greater concentration in black mustard cake
      protein whereas other amino acids were higher in yellow mustard cake protein. 

PMID- 25859423
TI  - Neurotensin receptors in pancreatic ductal carcinomas.
AB  - BACKGROUND: The frequent expression of neurotensin receptors (NT-R) in primaries
      of pancreatic ductal carcinomas has triggered the development of radioactive
      neurotensin analogs for possible in vivo targeting of these tumors. However, the
      complete lack of information regarding NT-R in liver metastases of pancreatic
      cancer and pancreatic intraepithelial neoplasia (PanIN) makes an in vitro study
      of NT-R in these tissues indispensable. METHODS: Using in vitro receptor
      autoradiography with (125)I-[Tyr(3)]-neurotensin, NT-R were investigated in 18
      primaries and 23 liver metastases of pancreatic ductal carcinomas as well as in
      19 PanIN lesions. RESULTS: We report here that 13 of 18 ductal carcinoma
      primaries and 14 of 23 liver metastases expressed NT-R. Moreover, none of the six
      PanIN 1B cases expressed NT-R, while two of six PanIN 2 and five of seven PanIN 3
      expressed NT-R. Binding was fully displaced by the type 1 NT-R-selective
      antagonist SR48692, indicating that the NT-R in the tumors are of the type 1 NT-R
      subtype. CONCLUSIONS: These in vitro data extend the currently available
      information on NT-R in invasive and non-invasive pancreatic ductal tumors. They
      suggest that type 1 NT-R may be a novel, specific marker of PanIN of higher
      degree. The high expression of NT-R in primaries and metastases of invasive
      cancer strongly support the need to develop radioactive neurotensin analogs for
      the diagnosis and therapy of this tumor type.

PMID- 25859424
TI  - Quantification of the effects of fur, fur color, and velocity on Time-Of-Flight
      technology in dairy production.
AB  - With increasing herd sizes, camera based monitoring solutions rise in importance.
      3D cameras, for example Time-Of-Flight (TOF) cameras, measure depth information.
      These additional information (3D data) could be beneficial for monitoring in
      dairy production. In previous studies regarding TOF technology, only standing
      cows were recorded to avoid motion artifacts. Therefore, necessary conditions for
      a TOF camera application in dairy cows are examined in this study. For this
      purpose, two cow models with plaster and fur surface, respectively, were recorded
      at four controlled velocities to quantify the effects of movement, fur color, and
      fur. Comparison criteria concerning image usability, pixel-wise deviation, and
      precision in coordinate determination were defined. Fur and fur color showed
      large effects (eta (2)=0.235 and eta (2)=0.472, respectively), which became even
      more considerable when the models were moving. The velocity of recorded animals
      must therefore be controlled when using TOF cameras. As another main result, body
      parts which lie in the middle of the cow model's back can be determined
      neglecting the effect of velocity or fur. With this in mind, further studies may
      obtain sound results using TOF technology in dairy production. 

PMID- 25859425
TI  - Life cycle of television public service announcements disseminated through
      donated airtime.
AB  - OBJECTIVE: To investigate the longevity and reach of television public service
      announcements (PSAs) developed by the Centers for Disease Control and
      Prevention's Screen for Life: National Colorectal Cancer Action Campaign.
      METHODS: Television airtime donated to Screen for Life PSAs was tracked, and the
      impressions (a broadcasting metric for audience size) generated by PSAs in
      circulation >= 5 years were analyzed in 2014. The sample consisted of 8 PSAs,
      including English and Spanish PSAs, PSAs featuring celebrities, and PSAs
      redistributed multiple times after their initial release. RESULTS: During the
      most recent year of circulation (5-9 years after initial release), each PSA
      generated 15.7 million to 251.7 million impressions. Peak annual impressions were
      achieved as late as 9 years after a PSA's initial release. When PSAs were
      redistributed 2 years or longer after the prior distribution, annual impressions
      increased over the preceding year by > 20 million in 80.0% of instances. Among
      English PSAs, those featuring celebrities produced the highest mean and peak
      annual impressions. CONCLUSIONS: Donated-placement television PSAs can be a long
      lived health promotion strategy. Redistribution may enhance PSA longevity, and
      featuring celebrities, particularly in English PSAs, may expand reach.

PMID- 25859426
TI  - A generalised enzyme kinetic model for predicting the behaviour of complex
      biochemical systems.
AB  - Quasi steady-state enzyme kinetic models are increasingly used in systems
      modelling. The Michaelis Menten model is popular due to its reduced parameter
      dimensionality, but its low-enzyme and irreversibility assumption may not always
      be valid in the in vivo context. Whilst the total quasi-steady state assumption
      (tQSSA) model eliminates the reactant stationary assumptions, its mathematical
      complexity is increased. Here, we propose the differential quasi-steady state
      approximation (dQSSA) kinetic model, which expresses the differential equations
      as a linear algebraic equation. It eliminates the reactant stationary assumptions
      of the Michaelis Menten model without increasing model dimensionality. The dQSSA
      was found to be easily adaptable for reversible enzyme kinetic systems with
      complex topologies and to predict behaviour consistent with mass action kinetics
      in silico. Additionally, the dQSSA was able to predict coenzyme inhibition in the
      reversible lactate dehydrogenase enzyme, which the Michaelis Menten model failed
      to do. Whilst the dQSSA does not account for the physical and thermodynamic
      interactions of all intermediate enzyme-substrate complex states, it is proposed
      to be suitable for modelling complex enzyme mediated biochemical systems. This is
      due to its simpler application, reduced parameter dimensionality and improved
      accuracy. 

PMID- 25859427
TI  - 'The great imitator': Neurosyphilis and new-onset refractory status epilepticus
      (NORSE) syndrome.
AB  - New-onset refractory status epilepticus (NORSE) is a syndrome of new-onset drug
      resistant status epilepticus that often has a catastrophic outcome. A 30-year-old
      man of Somali origin presented with refractory status to a district general
      hospital. A clinical diagnosis of NORSE syndrome was made, and he was transferred
      to the regional epilepsy center for immunomodulatory treatment and consideration
      for cyclophosphamide treatment. After transfer to the regional epilepsy center,
      his repeat cerebrospinal fluid tested strongly positive for syphilis, indicating
      a diagnosis of neurosyphilis, and the patient was treated with high-dose
      intravenous (IV) benzylpenicillin. His status epilepticus abated 24 h later. New
      onset refractory status epilepticus syndrome is a diagnosis of exclusion. Before
      instigation of potentially harmful neuromodulatory therapies, treatable causes
      such as neurosyphilis should be considered. We advocate the early transfer of
      refractory status patients to a specialist epilepsy center for both seizure
      management and cause determination. 

PMID- 25859428
TI  - Prolongation of Chemically-Induced Methemoglobinemia in Mice Lacking alpha
      synuclein: A Novel Pharmacologic and Toxicologic Phenotype.
AB  - The protein alpha -synuclein is considered central to the pathogenesis of
      Parkinson disease (PD) on genetic and histopathological grounds. It is widely
      expressed in fetal life and continues to be highly expressed in adult neural
      tissues, red blood cells and platelets, while the remainder of adult tissues are
      reported to have little or no expression. Despite cellular and molecular evidence
      for a role in neuronal function including synaptic vesicle trafficking,
      neurotransmitter release, mitochondrial function, lipid metabolism, neurogenesis,
      neuroprotection, and neuromelanin biosynthesis, mice ablated for the gene
      encoding alpha -synuclein (Snca) have little or no neurological phenotype. Thus,
      nearly 20 years of intensive study have yet to reveal conclusively what the
      normal function of this highly abundant protein is in the nervous system.
      Interestingly, alpha -synuclein has also been shown to have enzymatic activity as
      a ferrireductase capable of reducing Fe+3 to Fe+2. Given its abundant expression
      in red blood cells, we set out to explore the role of alpha -synuclein in
      converting chemically-induced Fe+3 methemoglobin to normal Fe+2 hemoglobin.
      Initial in vivo experiments with the potent methemoglobin inducer, para
      aminopropiophenone and its active metabolite, 4-hydroxy para-aminopropiophenone,
      demonstrated significantly greater and more prolonged methemoglobinemia in Snca-/
      mice compared to Snca+/+ mice. In vitro experiments with red blood cells,
      however, and in vivo experiments in genetically engineered mouse strains that
      differ in their alpha -synuclein expression in various tissues, including the
      nervous system, red blood cells and liver, revealed that contrary to the initial
      hypothesis, a lack of expression of alpha -synuclein in red blood cells did not
      correlate with higher levels or more prolonged duration of methemoglobinemia.
      Instead, the greater sensitivity to chemically induced methemoglobinemia
      correlated with the absence of hepatic alpha -synuclein expression. We have
      uncovered a new and robust whole-animal phenotype in mice lacking alpha 
      synuclein that reflects its hitherto unrecognized role in xenobiotic
      detoxification.

PMID- 25859429
TI  - The "Macro" World of microRNAs in Hepatocellular Carcinoma.
AB  - Hepatotropic viruses such as hepatitis B virus (HBV) and hepatitis C virus (HCV)
      are the major etiological agents associated with development of hepatocellular
      carcinoma (HCC). Progression of HCC is a multistep process that requires
      sequential or parallel deregulation of oncogenic and tumor suppressive pathways
      leading to chromosomal instability and neoplastic phenotype. In the recent years,
      microRNAs (miRNAs) have carved their own niche alongside oncogenes and tumor
      suppressors, owing to their innate ability to receive and relay multiple signals.
      Not surprisingly, miRNAs are fast emerging as central player in myriads of
      malignancies including HCC. miRNAs are reported to participate in initiation and
      progression of HCC, and have also been clinically correlated with risk
      assessment, disease grade, aggressiveness, and prognosis. Despite extensive data
      available on the role of miRNAs in HCC, there is a pressing need to integrate and
      evaluate these datasets to find its correlation, if any, with causal agents in
      order to devise novel interventional modalities. Through this review, we attempt
      to bridge the gap by consolidating the current knowledge and concepts in the
      field of HCC-related miRNAs with special emphasis on HBV and HCV. Further, we
      assess the potential of common as well as unique signatures that may be useful in
      developing novel biomarkers and therapeutics. 

PMID- 25859430
TI  - Feasibility and utility of telephone-based psychological support for people with
      brain tumor: a single-case experimental study.
AB  - Rates of psychological distress are high following diagnosis and treatment of
      brain tumor. There can be multiple barriers to accessing psychological support,
      including physical and cognitive impairments and geographical limitations. Tele
      based support could provide an effective and more flexible option for delivering
      psychological interventions. The present study aimed to investigate the
      feasibility and utility of a telephone-based psychotherapy intervention for
      people with brain tumor. A single-case multiple-baseline design was employed with
      a 4-7-week baseline phase, 10-week treatment phase, and 5-week maintenance phase
      including a booster session. Four participants with a benign or malignant brain
      tumor (three males and one female; aged 34-49 years), received 10 sessions of
      tele-based therapy and a booster session at 4 weeks post-treatment. Levels of
      depression, anxiety, and illness cognitions were monitored on a weekly basis
      throughout each phase whilst measures of quality of life, stress, and self
      concept were administered at the start and end of each phase. Weekly measures
      were analyzed using a combination of both visual analysis and Tau-U statistics.
      Of the four participants, two of them demonstrated significant gains in mental
      health (depression and/or anxiety) and a significant decrease in their levels of
      helplessness (p < 0.05). The other two participants did not show gains in mental
      health or change in illness cognitions. All participants reported improvement in
      quality of life post-treatment. The results of the study provide preliminary
      support concerning the feasibility and utility of tele-based therapy for some
      people with brain tumor. Further research examining factors influencing the
      outcomes of tele-based psychological support is needed. 

PMID- 25859432
TI  - Epstein-barr virus in gastro-esophageal adenocarcinomas - single center
      experiences in the context of current literature.
AB  - Epstein-Barr virus (EBV)-associated gastric carcinomas (GC) represent a distinct
      and well-recognized subtype of gastric cancer with a prevalence of around 10% of
      all GC. In contrast, EBV has not been reported to play a major role in esophageal
      adenocarcinomas (EAC) and adenocarcinomas of the gastro-esophageal junction
      (GEJ). We report our experiences on EBV in collections of gastro-esophageal
      adenocarcinomas from two surgical centers and discuss the current state of
      research in this field. Tumor samples from 465 primary resected gastro-esophageal
      adenocarcinomas (118 EAC, 73 GEJ, and 274 GC) were investigated. Presence of EBV
      was determined by EBV-encoded small RNAs (EBER) in situ hybridization. Results
      were correlated with pathologic parameters (UICC pTNM category, Her2 status,
      tumor grading) and survival. EBER positivity was observed in 14 cases. None of
      the EAC were positive for EBER. In contrast, we observed EBER positivity in 2/73
      adenocarcinomas of the GEJ (2.7%) and 12/274 GC (4.4%). These were of intestinal
      type (seven cases) or unclassifiable (six cases), while only one case was of
      diffuse type according to the Lauren classification. No association between EBV
      and pT, pN, or tumor grading was found, neither was there a correlation with
      clinical outcome. None of the EBER positive cases were Her2 positive. In
      conclusion, EBV does not seem to play a role in the carcinogenesis of EAC.
      Moreover, adenocarcinomas of the GEJ show lower rates of EBV positivity compared
      to GC. Our data only partially correlate with previous reports from the
      literature. This highlights the need for further research on this distinct
      entity. Recent reports, however, have identified specific epigenetic and genetic
      alterations in EBV-associated GC, which might lead to a distinct treatment
      approach for this specific subtype of GC in the future. 

PMID- 25859433
TI  - Suggested safe harbor limit for titanium dioxide: an exposure level which
      protects consumers from cancer incidence.

PMID- 25859431
TI  - Psychological intervention for improving cognitive function in cancer survivors:
      a literature review and randomized controlled trial.
AB  - Although the impact of cancer and associated treatments on cognitive functioning
      is becoming an increasingly recognized problem, there are few published studies
      that have investigated psychological interventions to address this issue. A
      waitlist randomized controlled trial methodology was used to assess the efficacy
      of a group cognitive rehabilitation intervention ("ReCog") that successfully
      targeted cancer-related cognitive decline in previously published pilot research.
      Participants were 29 cancer survivors who were randomly allocated to either the
      intervention group or a waitlist group who received the intervention at a later
      date, and 16 demographically matched community volunteers with no history of
      cancer (trial registration ACTRN12615000009516, available at
      http://www.ANZCTR.org.au/ACTRN12615000009516.aspx). The study was the first to
      include an adapted version of the Traumatic Brain Injury Self-Efficacy Scale to
      assess cognitive self-efficacy (CSE) in people who have experienced cancer.
      Results revealed participating in the intervention was associated with
      significantly faster performance on one objective cognitive task that measures
      processing speed and visual scanning. Significantly larger improvements for the
      intervention group were also found on measures of perceived cognitive impairments
      and CSE. There was some evidence to support the roles of CSE and illness
      perceptions as potential mechanisms of change for the intervention. Overall, the
      study provided additional evidence of feasibility and efficacy of group
      psychological intervention for targeting cancer-related cognitive decline. 

PMID- 25859434
TI  - Transcriptomic analysis of three Veillonella spp. present in carious dentine and
      in the saliva of caries-free individuals.
AB  - Veillonella spp. are predominant bacteria found in all oral biofilms. In this
      study, a metatranscriptomic approach was used to investigate the gene expression
      levels of three oral Veillonella spp. (V. parvula, V. dispar and V. atypica) in
      whole stimulated saliva from caries-free volunteers and in carious lesions (n =
      11 for each group). In the lesions the greatest proportion of reads were assigned
      to V. parvula and genes with the highest level of expression in carious samples
      were those coding for membrane transport systems. All three Veillonella spp.
      increased expression of genes involved in the catabolism of lactate and
      succinate, notably the alpha- and beta-subunits of L(+)-tartrate dehydratase (EC
      4.2.1.32). There was also significantly increased expression of histidine
      biosynthesis pathway in V. parvula, suggesting higher intra-cellular levels of
      histidine that could provide intra-cellular buffering capacity and, therefore,
      assist survival in the acidic environment. Various other systems such as
      potassium uptake systems were also up regulated that may aid in the survival and
      proliferation of V. parvula in carious lesions. 

PMID- 25859436
TI  - Versatile but temperamental: a morphological study of palmaris longus in the
      cadaver.
AB  - INTRODUCTION: Palmaris longus (PL) is one of the most variable muscles in our
      body and is vestigial functionally. Its long tendon and its superficial location
      make it an ideal source for tendon harvesting. Variations such as absence,
      duplication and reversal have far reaching clinical impact. The aim of this study
      is to estimate the presence, variants and nerve supply of the PL. MATERIALS AND
      METHODS: Upper extremity of 24 cadavers was dissected and PL was examined. The
      results were compared to other studies on the PL and literature survey was
      carried out. RESULTS: Thirty nine specimens showed normal morphology and four
      showed complete agenesis. Other morphological variations seen included -
      reversed, hybrid, fusiform, fleshy and bifurcated tendon of insertion.
      CONCLUSION: Every surgeon must be aware of the variations of the versatile but
      temperamental PL. Prior knowledge of the layout of the muscle helps in planning
      intricate surgeries to which this tendon is put use to.

PMID- 25859437
TI  - A morphologic and morphometric study of foramen vesalius in dry adult human
      skulls of gujarat region.
AB  - INTRODUCTION: The foramen Vesalius is located within bony plate between the
      foramen ovale and the foramen rotundum in the floor of middle cranial fossa. This
      foramen allows passage of emissary veins which communicate cavernous sinus and
      pterygoid plexus of veins. AIM: To study the morphological and morphometric
      variations of foramen Vesalius in dry adult human skulls. MATERIALS AND METHODS:
      One hundred and fifty dry adult human skulls were studied for variations in size,
      shape, presence/absence and any duplication/multiplication of the foramen
      Vesalius. After collecting data, appropriate statistical analysis was done.
      RESULTS: The mean maximum dimension of foramen Vesalius was 0.98+/-0.67 mm on
      right side and 1.12+/-0.73 mm on left side. Foramen Vesalius was present in 90
      (60%) skulls out of 150 observed. The incidence was 41(27.33%) on right side and
      49 (32.67%) on left side. Foramen Vesalius was present unilaterally in 32
      (35.56%) and bilaterally in 29 (32.23%) out of 90 skulls. Duplication of this
      foramen was observed in two skulls (one right side and one on left side). Foramen
      Vesalius was round in 72%, oval in 24% and irregular in 4% of total foramina
      present. CONCLUSION: Foramen Vesalius was present in 60% of total skulls studied.
      The foramen showed variations in incidence and shapes, while there was no
      statistically significant difference in the maximum dimension between foramen
      Vesalius on right and left side. There could be some developmental reasons to
      explain these variations. The findings of this study could be important to
      anatomists and also equally essential for clinicians who approach middle cranial
      cavity for various procedures.

PMID- 25859435
TI  - Lactobacillus protects the integrity of intestinal epithelial barrier damaged by
      pathogenic bacteria.
AB  - Pathogens invade intestinal mucosal barrier through phagocytosis of antigen
      presenting cells (dendritic cell, microfold cells), or through the invasion into
      the intestinal epithelial directly. Some pathogens could damage the cell junction
      between epithelial cells and use the paracellular pathway as an entrance to
      invade. Moreover, some Lactobacillus could inhibit the adhesion of the pathogens
      and protect the integrity of the cell junction and mucosal barrier. This research
      focused on the potential therapeutic effect of Lactobacillus fructosus (L.
      fructosus) C2 to attenuate ETEC K88 or S. typhimurium SL1344 induced changes to
      mucosal barrier. The results demonstrated that treatment of polarized Caco-2
      cells with L. fructosus C2 reduced the permeation of dextran, and expression of
      IL-8, p-ERK, and p-JNK when cells were infected with pathogenic bacteria. The
      findings indicated that L. fructosus C2 exerted a protective effect against the
      damage to the integrity of Caco-2 cells by ETEC or S. typhimurium infection. 

PMID- 25859438
TI  - Variations of gonadal veins: embryological prospective and clinical significance.
AB  - INTRODUCTION: An adequate knowledge of anomalies of gonadal veins will help the
      radiologists and surgeons in recognition and protection of these veins which play
      major roles in thermo-regulation that is essential for the efficient functioning
      of testis on which the survival of the human species depends. AIM: The aim of
      this work is to present an analysis of the anatomical variations of gonadal
      veins. An effort has also been made to explicate the possible embryological model
      of development of such variants and to present the variable clinical aspects
      concerning them. MATERIALS AND METHODS: Gonadal veins in 60 dissection room
      cadavers were examined for variations from the classic anatomic description.
      RESULT: In the present study, out of 60 cases, male: female ratio was 2:1(40:20)
      in which no variation was found in ovarian veins. In the 18 (45%) cases,
      testicular veins showed variations which consist of duplication and atypical
      drainage. DISCUSSION: Variations of drainage of gonadal vein are due to error of
      embryological development in venous shift and alteration in anastomotic channel
      of post-cardinal, supra-cardinal and sub cardinal veins. CONCLUSION: The gonadal
      veins present numeric variations as well as variations in its site of drainage,
      which attributed to the various pathological conditions as varicocele and pelvic
      congestion syndrome, leading to infertility in patients. Hence, in -depth
      knowledge of these developmental anomalies of gonadal veins is important.

PMID- 25859439
TI  - A glimpse towards the vestigiality and fate of human vermiform appendix-a
      histomorphometric study.
AB  - INTRODUCTION: The vermiform appendix in human is considered to be a vestigial
      organ by most of the authors. Absence of appendix is already reported in Indian
      population. Whether the human appendix is performing any function is debatable
      but when present it can create trouble. So if there is no appendix we can escape
      the ill-effects of the organ. With this hope the study has been done to see
      whether the appendix is really going to be rudimentary or absent or not.
      Marerials and Methods: Length, external diameter, number of lymphoid follicles,
      maximum diameter of the follicle or submucous coat, thickening of the muscle coat
      and seromucosal thickening of freshly removed appendix from human cadavers were
      seen. After fixation in 10% formal saline tissues were stained with haematoxylin
      eosin stain and photographs were taken. The results had been tabulated and
      statistically correlated. RESULT: The parameters like number of lymphoid
      follicles, length and diameter all are changed as per the age advancement which
      is strictly indicating some functional activities of the organ which is against
      the idea of vestigiality of the appendix. CONCLUSION: Human appendix cannot be
      called a vestigial organ unless the functional inactivity is proved. Lymphoid
      changes which occur after birth to provide the gut immunity is needed to be
      proved by further studies. There might be incidental absence or rudimentary
      appendix in human body, but that does not indicate that we would not have any
      appendix in future.

PMID- 25859440
TI  - Study of Morphometry of Carotid Canal in Skulls of South Indian origin.
AB  - BACKGROUND: The internal carotid artery supplies the anterior part of the brain,
      the eye and its appendages and sends branches to the forehead and nose.Carotid
      canal is a curved channel in the petrous temporal bone through which internal
      carotid artery enters the skull. AIM: In the present study 20 skulls of unknown
      sex were considered. The morphometric study of carotid canal was studied by
      direct bone method and by silicone cast method. The present study aimed to show
      the differences of measurements by two methods and the silicon cast method is of
      its kind to measure the length of the carotid canal. MATERIALS AND METHODS:
      Carotid canal were measured at three different levels by both methods. Length of
      carotid canal to bend, diameter at the bend, length from the bend to foramen
      lacerum. The data was analysed for all the measurements of two methods and
      comparison of mean and SD at three different levels was done.Significant
      difference between two methods at three different levels was observed.
      Independent sample t-test was applied for total length of carotid canal. RESULTS:
      By observation there is a mean significant difference between two methods in the
      measurements of carotid canal from lower opening till the angulation on left side
      of the skull.The study showed that there is a bilateral significant difference in
      measurements of diameter between two methods. There was no significant difference
      observed in total length of the canal in both left and right sides. CONCLUSION:
      Morphometrical details of the canal are of great significance to neurosurgeons
      and otologists. Silicon cast method was cost effective and much easier method to
      study the length and measurements of carotid canal as it exactly depicts the
      curvature of carotid canal.

PMID- 25859441
TI  - Multiple variations in the pelvic vasculature - a case report.
AB  - A thorough knowledge of possible variations of pelvic vasculature is very useful
      for surgeons, gynaecologists, radiologists, urologists and orthopaedic surgeons.
      We report multiple vascular variations in the left half of the pelvis of an adult
      male cadaver. Iliolumbar artery arose from the main trunk of the internal iliac
      artery. Posterior division of the internal iliac artery gave two lateral sacral
      arteries and a superior gluteal artery. The anterior division of the internal
      iliac artery gave origin to superior vesical, inferior vesical, inferior gluteal
      and internal pudendal arteries. The internal pudendal artery gave origin to a
      common trunk before leaving the pelvis. The common trunk divided into middle
      rectal artery and deep artery of the penis. The obturator artery took origin from
      the inferior epigastric artery and descended downward to the pelvis and left the
      pelvis by passing through the obturator foramen. Most of the other veins
      accompanying the arteries joined to form a plexus on the superior surface of the
      pelvic diaphragm. This plexus condensed to form anterior and posterior divisions
      of the internal iliac vein. Apart from this, the posterior part of the plexus
      drained directly into the common iliac vein through a large unnamed vein. 

PMID- 25859442
TI  - Oxidative stress and nutritional status in chronic obstructive pulmonary disease.
AB  - BACKGROUND: Oxidative stress and malnutrition are shown to have pathogenic effect
      in Chronic Obstructive Pulmonary Disease (COPD). AIM: This study was done to
      assess the burden of oxidative stress in COPD and to determine its relation to
      their nutritional status. MATERIALS AND METHODS: In this cross-sectional study,
      100 COPD cases from emergency and medical ward and meeting inclusion criteria,
      along with age, sex and occupation (mainly farmers, housewives and drivers)
      matched 100 controls without COPD and meeting inclusion criteria were enrolled.
      Oxidative stress was assessed by measuring lipid peroxidation product,
      Malondialdehyde (MDA) and antioxidants, like Vitamin C, E and Red Blood Cell
      Catalase (RBCC). Mini Nutritional Assessment (MNA) tool and Body Mass Index (BMI)
      were used to assess nutritional status. STATISTICAL ANALYSIS: Chi-square test was
      applied for categorical variable. Student t-test was applied for comparison of
      means. Analysis of Variance (ANOVA) was applied for comparison between groups
      followed by Bonferroni post hoc analysis. Pearson correlation method was used for
      quantitative variables. Statistical significance was defined as p< 0.05 (two
      tailed). RESULTS: COPD cases had significantly high MDA level with low level of
      Vitamin E and catalase as compared to controls (p < 0.001). Most of the COPD
      cases were underweight (BMI <= 18.5 Kg/m(2)) and malnourished (MNA score less
      than 7). Bonferroni post-hoc analysis, showed significantly high burden of
      oxidative stress in underweight and malnourished cases as compared to normal
      weight (p < 0.05) among COPD cases. Highly significant correlation was seen
      between BMI and plasma MDA level (r = -0.27, p = 0.008) in COPD cases.
      CONCLUSION: This study shows impaired oxidant/antioxidant balance along with
      malnutrition and underweight in COPD, which signals for considering antioxidant
      therapy along with nutritional management.

PMID- 25859443
TI  - Plasma Levels of Uric Acid, Urea and Creatinine in Diabetics Who Visit the
      Clinical Analysis Laboratory (CAn-Lab) at Kwame Nkrumah University of Science and
      Technology, Kumasi, Ghana.
AB  - INTRODUCTION: Diabetes mellitus is one of the most common metabolic diseases
      worldwide. This metabolic disorder contributes greatly to the significant
      proportion of the burden of renal damage and dysfunction. The aim of the study
      was to investigate the renal function of the diabetic patients who visit the
      Clinical Analysis Laboratory (CAn-Lab) at the Kwame Nkrumah University of Science
      and Technology (KNUST), Kumasi, Ghana. MATERIALS AND METHODS: Demographic data as
      well as medical history were obtained through the administration of a
      questionnaire. Anthro-pometric measurements were taken and blood samples were
      analysed for glucose, uric acid, urea and creatinine. Data collected were
      analysed using SPSS version 16.0. RESULTS: A total of 34 diabetic patients, aged
      from 40-77 y were recruited, 22 (64.7%) of them were males with mean age of 57.40
      +/- 11.8 y (+/-SD), while 12 (35.3%) were females with mean age of 58.17 +/- 7.47
      y. There was a statistically significant difference between the mean duration of
      the disease, as the females had longer duration, 12.50 +/- 6.95 y, as compared to
      7.32 +/- 4.48 y in males (p=0.033). The mean plasma creatinine level in the
      females was 84.17 +/- 54.73 MUmol/l. In the diabetic population, there was a
      positive correlation between age and plasma creatinine level, (r=0.375, p=0.029).
      In the female diabetics, there was a positive correlation between fasting blood
      sugar (FBS) and the measured metabolic end products (r>0.5, p<0.05), a positive
      correlation between body mass index (BMI) and uric acid (r=0.576, p=0.005) and a
      positive correlation between BMI and FBS (r= 0.625, p= 0.030). CONCLUSION: Our
      results on the parameters measured; show that the diabetic population was
      experiencing mild kidney dysfunction, compared to non-diabetic controls.

PMID- 25859444
TI  - Study on serum cortisol and perceived stress scale in the police constables.
AB  - INTRODUCTION: The occupational stress may be more among the police constables.
      Under the stressed conditions, the body secretes more Cortisol. Elevated serum
      cortisol levels significantly correlate with the symptoms of metabolic Syndrome.
      Perceived stress scale (PSS) is the most widely used psychological tool for
      measuring the perception of stress. The objective of this study was to examine
      the association between perceived stress and Serum Cortisol and also to explore
      stress as an occupational risk factor which may lead to metabolic syndrome.
      MATERIALS AND METHODS: We measured Serum Cortisol, Lipid profile, Blood Glucose
      and HbA1c in both Police constables and the general population. Also to evaluate
      the occupational stress, the questionnaire consisting of Perceived stress scale 
      14 items was used. RESULTS: A positive correlation was found between Serum
      Cortisol and perceived stress scale, Blood Glucose, HbA1c. The biochemical
      parameters were found to be elevated in police constables compared to controls.
      It was found that among 108 policemen, 38% were confirmed with cardiometabolic
      syndrome. CONCLUSION: The relation between Serum Cortisol and perceived stress
      scale indicates the severity of occupational stress the police constables are
      experiencing. So the occupation based health program for lifestyle changes,
      modification in job related rules and regulations will help to avert further
      complications and keep police personnel healthy.

PMID- 25859445
TI  - Evidence of Paternal N5, N10 - Methylenetetrahydrofolate Reductase (MTHFR) C677T
      Gene Polymorphism in Couples with Recurrent Spontaneous Abortions (RSAs) in Kolar
      District- A South West of India.
AB  - INTRODUCTION: Recurrent spontaneous abortion (RSA) is a multifactorial clinical
      obstetrics complication commonly occurring in pregnancy. Many research studies
      have noted the mutations such as C677T in N5, N10 - Methylenetetrahydrofolate
      reductase (MTHFR)gene which is regarded as RSA risk factor. This study was
      carried out to determine the occurrence of frequency of C677T of the MTHFR gene
      mutations with RSA. AIM: The purpose of present study is to determine the
      frequency of MTHFR C677T polymorphisms in couples with recurrent pregnancy loss
      and the impact of paternal polymorphisms of MTHFR C677T in recurrent pregnancy
      loss in population of couples living in Kolar district of Karnataka with RSA.
      DESIGN: A total of 15 couples with a history of two or more unexplained RSA were
      enrolled as subjects in the study and a total of 15 couples with normal
      reproductive history, having two or more children and no history of miscarriages
      were enrolled as controls. MATERIALS AND METHODS: DNA extraction from samples
      case and control group couples and its quantification by Agarose gel
      electrophoresis, assessment of DNA purity, MTHFR C 677T gene mutation detection
      by PCR-RFLP method. STATISTICAL ANALYSIS: Carried out by web based online SPSS
      tool. RESULTS: The frequency of C677T genotype showed homozygous wild type CC
      (80%), heterozygous CT type (13.3%) and homozygous mutation TT type (6.67%)
      observed in males. Similarly from female's homozygous wild type CC (86.6%),
      heterozygous type (13.3%), and homozygous type mutations TT (0%) was recorded. In
      couple control groups, we observed homozygous wild type CC (86.6%), heterozygous
      CT type (13.3%) and homozygous type mutations TT type (0%). CONCLUSION: We
      noticed a high frequency of MTHFR specifically T allele associated with paternal
      side.Therefore, the present study indicated the impact of paternal gene
      polymorphism of MTHFR C677T on screening in couples with recurrent pregnancy
      loss.

PMID- 25859446
TI  - Effect of cell phone use on salivary total protein, enzymes and oxidative stress
      markers in young adults: a pilot study.
AB  - INTRODUCTION: The present study aimed to assess the levels of salivary enzymes,
      protein and oxidant-antioxidant system in young college-going cell phone users.
      MATERIALS AND METHODS: The cell users (students) were categorized in to two
      groups - less mobile users and high mobile users, based on the duration and
      frequency of cell use. Unstimulated whole saliva samples of the volunteers were
      analysed for amylase, lactate dehydrogenase (LDH), malondialdehdye (MDA) and
      glutathione (GSH). RESULTS: High mobile users had significantly higher levels of
      amylase (p = 0.001), LDH (p = 0.002) and MDA (p = 0.002) in saliva, when compared
      to less mobile users. The marginal decrease in salivary total proteins, GSH and
      flow rate were statistically not significant (p >0.05). CONCLUSION: Significant
      changes in salivary enzymes and MDA suggest adverse effect of high use of cell
      phones on cell health.

PMID- 25859447
TI  - Identification of Predictable Biomarkers in Conjunction to Framingham Risk Score
      to Predict the Risk for Cardiovascular disease (CVD) in Non Cardiac Subjects.
AB  - INTRODUCTION: Although the cardiovascular disease (CVD) burden is rising in
      different countries, the morbidity and mortality rate is not reduced to much
      extent because of lack of application of the biomarkers for diagnosing CVD.
      Hence, we aimed to establish the predictable biomarkers in conjunction to
      framingham risk score in order to predict the risk for CVD in non cardiac
      patients. MATERIALS AND METHODS: Three hundred subjects were screened for the
      study who came for the master health checkup. Out of them 50 patients were
      excluded as they were under medication. 23 patients were excluded due to various
      systemic diseases like fever and infection etc. The remaining of 227 patients
      with age range of 30-80 y was randomly selected for investigation. These subjects
      were divided into four different groups: Group I - controls with age range: 30-60
      y (n=50) these subjects were free from all the systemic ailments and risk
      factors. Study groups comprised of Group II - (n=44) with age range: 30-40 y,
      Group III - (n=50) with age range: 41-50 y and Group IV - (n=83) with age range:
      51-80 y. Patients with different risk factors without medication participated as
      study groups. Routine biochemical parameters were analysed using fully automated
      analyser and atherosclerotic biomarkers was analysed using ELISA kit. In addition
      to this, framingham risk scores was calculated in all the groups, for 30 y risk
      prognosis for CVD. RESULTS: The atherosclerotic biomarkers such as E-selectin,
      Leptin, osteoprotegerin (OPG) and Ox-LDL were elevated among the study groups as
      compared to control group. Pearson correlation showed a significant association
      between the individual risk score (30 y framingham risk for CVD) of individuals,
      and the above biomarkers. The Receiver operating curve (ROC) analysis also showed
      a greater area under curve with higher sensitivity and specificity. CONCLUSION:
      We conclude the application E-Selectin, leptin, OPG and Ox-LDL as biomarkers
      along with the framingham risk scores in prediction risk for CVD in the
      individuals with subclinical atherosclerosis. It is more reliable and predictable
      as compared to the individual biomarkers alone.

PMID- 25859448
TI  - Agreement of arterial sodium and arterial potassium levels with venous sodium and
      venous potassium in patients admitted to intensive care unit.
AB  - INTRODUCTION: Electrolyte abnormalities are one of the common causes of morbidity
      and mortality in critically ill patients. The turnaround time for electrolyte
      reporting should be as low as possible. Electrolytes are measured conventionally
      in serum obtained from venous blood by electrolyte analyser which takes 20 to 30
      min. Point of care analysers are now available where in electrolytes can be
      measured in arterial blood within 5 min. This study was done to study the
      agreement of arterial sodium and arterial potassium with venous sodium and venous
      potassium levels. MATERIALS AND METHODS: Venous sodium and venous potassium
      levels and arterial sodium and arterial potassium levels were analysed on 206
      patient samples admitted to Intensive Care Unit (ICU). The venous values were
      compared with the arterial values for correlation. Venous sodium was compared
      with arterial sodium by spearman correlation. Venous potassium was compared with
      arterial potassium by pearson correlation. RESULTS: The mean value of arterial
      sodium was 134 and venous sodium was 137. The mean value of arterial potassium
      was 3.6 and venous potassium was 4.1. The correlation coefficient obtained for
      sodium was 0.787 and correlation coefficient obtained for potassium was 0.701.
      There was positive correlation of arterial sodium and arterial potassium with
      venous sodium and venous potassium indicating agreement between the parameters.
      CONCLUSION: Arterial sodium and arterial potassium can be used instead of venous
      sodium and venous potassium levels in management of critically ill patients.

PMID- 25859449
TI  - Efficacy of garcinia cambogia on body weight, inflammation and glucose tolerance
      in high fat fed male wistar rats.
AB  - INTRODUCTION: Obesity leads to derangements in lipid and glucose homeostasis
      resulting in various metabolic complications. Plants containing vital
      phytochemicals are known to posses anti obesity properties and have proved to
      exert beneficial effects in obesity. OBJECTIVES: The present study was aimed to
      investigate the effects of Garcinia Cambogia on body weight, glucose tolerance
      and inflammation in high fat diet fed male Wistar rats. MATERIALS AND METHODS:
      Five month old male wistar rats (n=40) were divided into four groups. Two groups
      were fed with standard rodent diet and the remaining two with 30% high fat diet.
      One group in each of the two sets received the crude ethanolic extract of
      Garcinia Cambogia at a dose of 400mg/kg body weight/day for ten weeks. Body
      weight, intraperitoneal glucose tolerance test, leptin, tumour necrosis factor
      alpha (TNF-alpha) and renal function (urea, creatinine, uric acid) were studied.
      RESULTS: High fat diet fed rats showed increased body weight gain, glucose
      intolerance, elevated levels of plasma leptin and TNF-alpha. Supplementation of
      Garcinia Cambogia extract (GE) along with high fat diet significantly decreased
      body weight gain, glucose intolerance, plasma leptin and TNF-alpha level. No
      significant changes were observed in the renal function parameters in any of the
      groups. CONCLUSION: Supplementation of the Garcinia Cambogia extract with high
      fat diet reduced body weight gain, inflammation and glucose intolerance.

PMID- 25859450
TI  - Effect of yoga module on pro-inflammatory and anti-inflammatory cytokines in
      industrial workers of lonavla: a randomized controlled trial.
AB  - INTRODUCTION: Inflammatory markers play a very important role in body's defense
      mechanism. Pro-inflammatory markers and anti-inflammatory markers counterbalance
      each other. It is extremely essential for the body to maintain their balance for
      a good immune response. OBJECTIVES: To study the effect of yoga practices on
      selected pro-inflammatory and anti-inflammatory cytokine among industrial
      workers. MATERIALS AND METHODS: Forty eight male study participants, aged 30-58
      years, were randomly divided into experimental (n=24) & control (n=24) groups.
      Pro-inflammatory cytokine IL-1beta and anti-inflammatory cytokine IL-10 were
      evaluated at the baseline and at the end of 12 wk of yoga training in both the
      groups. During the experimental study, all the study participants continued with
      their daily lifestyle and diet. Data were analysed using paired t-test and
      independent t-test. RESULTS: The result of within group comparison revealed that
      the yoga group showed a significant decrease in IL-1 beta while significant
      increase in IL-10 (p < 0.05), whereas the control group revealed no change in IL
      1 beta (p > 0.05) and IL-10 (p > 0.05). Further, the results between the groups
      confirmed that the yoga group had significantly lower level of IL-1 beta and
      increase in IL-10 as compared to control group (p < 0.05). CONCLUSION: The
      present study has demonstrated that yoga practices could reduce pro-inflammatory
      cytokine and increase anti-inflammatory cytokine in industrial workers.

PMID- 25859451
TI  - High Prevalence of Symptomatic Hepatitis A Infection in Rural Area of Chaharmahal
      VA Bakhtiari Province, Iran.
AB  - INTRODUCTION: Hepatitis A virus (HAV) is the most common cause of hepatitis
      during childhood and is an important public health problem. Therefore, the aim of
      this study was to investigate an outbreak of symptomatic viral hepatitis in
      children and in young adults in a rural area from Chaharmahal Va Bakhtiari
      Province, Iran. MATERIALS AND METHODS: Serum samples from the 70 patients with
      icterus, who were suspected for HAV infection, referred to a therapeutic center
      in a central province of Iran from February to July, 2010 were tested for IgM
      specific antibody to HAV, using Enzyme linked Fluorscent assay (ELFA) Kit
      (General Biological Corp., Hsinchu, Taiwan). RESULTS: All of the 70 children had
      jaundice. The ELFA results showed that 48 out of 70 (68.6%) tested positive for
      anti-HAV specific antibody (IgM). The mean age of the individuals were 12.81+12.2
      and 23 of them (32.8%) were females. There was significant relationship between
      seropositivity for IgM anti-HAV antibody and age group in the patients studied
      (p<0.05). CONCLUSION: The high number of cases identified, may indicate an
      outbreak of hepatitis A in this region with the children as the most susceptible
      age group to this symptomatic infection.

PMID- 25859452
TI  - Prevalence of clostridium difficile among paediatric patients in a tertiary care
      hospital, coastal karnataka, South India.
AB  - INTRODUCTION: The study was intended to analyse the burden of Clostridium
      difficile (C. difficile) and associated intestinal pathogens from children with
      diarrhoea who were hospitalized in a tertiary care teaching hospital of South
      India. MATERIALS AND METHODS: Stool samples from 138 children with diarrhoea
      belonging to the age group 0-14 years were analysed by semi quantitative culture,
      latex agglutination and enzyme immunoassay for C. difficile. The associated
      intestinal pathogens were also detected from the specimens by standard
      procedures. RESULTS: Stool samples of 138 children were tested during the period;
      21 (15.22%) samples were culture positive for C. difficile and the isolates were
      confirmed by biochemical reactions. 9(6.52%) were positive by latex
      agglutination. EIA for C. difficile toxins A and B was done on all the stool
      specimens and 15 were found to be positive (10.87 %). According to the reference
      standard method employed in our study, 4 toxigenic C. difficile isolates (2.90%)
      were obtained from 138 specimens. Among the other intestinal pathogens,
      Escherichia coli predominated (22.46%). Rota virus was detected in 7.27% stool
      samples of children under the age of five years. CONCLUSION: The study shows the
      prevalence of C. difficile in hospitalized children in our locality which
      highlights the importance of judicious use of antibiotics and strict infection
      control measures.

PMID- 25859453
TI  - Relationship between Antimicrobial Consumption and the Incidence of Antimicrobial
      Resistance in Escherichia coli and Klebsiella pneumoniae Isolates.
AB  - INTRODUCTION: Gram negative organisms are one of the major causes of nosocomial
      diseases. Development of resistance to antibiotics by these organisms increases
      their risk in clinical treatment of patients. It also affects morbidity and
      mortality hence needs to be monitored and controlled. AIM: The aim of the present
      study was to analyse the correlation between consumption of parenteral
      antibiotics and the rates of antimicrobial resistance among the Escherichia coli
      and Klebsiella pneumoniae isolates collected during Dec 2010 - Jun 2013 from
      JIPMER hospital. MATERIALS AND METHODS: Consumption data of parenteral
      antibiotics in J01 category of Anatomical Therapeutic Chemical (ATC) in JIPMER
      was obtained and expressed in Defined Daily Doses (DDD) per 1000 inhabitants.
      Valid consumption and resistance data during the period Dec 2010 to Jun 2013 were
      obtained at 6 month intervals and were correlated to draw a relationship between
      antimicrobial consumption and its impact on drug resistance for Escherichia coli
      and Klebsiella pneumoniae. RESULTS: Escherichia coli isolates showed high
      resistance for increased use of gentamycin and ciprofloxacin. Increase in
      antibiotic consumption increases the resistance for Escherichia coli except for
      amikacin. Among the Klebsiella isolates, meropenem and gentamycin showed high
      correlations followed by ceftazidime, amikacin, ceftriaxone and ciprofloxacin.
      CONCLUSION: In summary, a statistically significant association was noticed
      between consumption of the studied antimicrobials and resistance of Escherichia
      coli isolates, except for amikacin and ceftazidime. In the case of Klebsiella
      pneumoniae, there was a statistically significant association between the
      resistance rates and consumption of gentamycin, ceftazidime and meropenem.
      Further, a linear relationship was noted between antimicrobial consumption and
      resistant isolates of Escherichia coli and Klebsiella pneumoniae, except for
      Escherichia coli resistance to amikacin.

PMID- 25859454
TI  - In Vitro Fractional Inhibitory Concentration (FIC) Study of Cefixime and
      Azithromycin Fixed Dose Combination (FDC) Against Respiratory Clinical Isolates.
AB  - INTRODUCTION: Acute respiratory infections (ARI) contribute to more than 75% of
      health care seeking in primary health care facilities in India. Respiratory tract
      infections (RTIs) are managed frequently by beta-lactam, macrolide and
      fluroquinolone class of antibiotics. However, these recommended classes of
      antibiotic have shown resistance in community settings. Antibiotic combinations
      may provide broader spectrum not only in terms of coverage but also to overcome
      multiple resistance mechanisms overcoming individual class limitations. AIM: The
      study aimed to determine In vitro interactions interpreted according to
      calculated fractional inhibitory concentration (FIC) index between cefixime and
      azithromycin against common respiratory clinical isolates. MATERIALS AND METHODS:
      Forty four bacterial respiratory clinical isolates from microbiology department
      of tertiary care hospital from Mumbai were used to determine the minimum
      inhibitory concentration (MIC) values of cefixime and azithromycin. Synergy
      testing of cefixime combination with azithromycin was performed by checkerboard
      method. Interaction was determined according to calculated FIC index. RESULTS:
      MIC values were ranging from 2-128 MUg/ml and 0.24-128 MUg/ml for cefixime and
      azithromycin respectively against K.pneumoniae, M.catarrhalis, S.pneumoniae and
      H.influenzae isolates. All the tested isolates were resistant to cefixime.
      Azithromycin resistance was noted in all the isolates except six M. catarrhalis
      isolates. FIC index showed synergy and additive effect in 66% (29/44) and 34%
      (15/44) all bacterial clinical isolates. Maximum synergy between cefixime and
      azithromycin was observed against K. pneumoniae in 91% isolates. CONCLUSION: This
      is one of the first attempts to check the rationality of fixed dose antibiotic
      combination of cefixime and azithromycin in India market. Though results of this
      study cannot be generalized considering the limitations of low sample size and in
      vitro model, our data provides stepping stone for further validation of cefixime
      and azithromycin fixed dose combinations (FDCs) in clinical setting by conducting
      randomized controlled trials. We think that judicious and rational use of FDCs
      may help to reduce the risk of selection of further drug resistance along with
      better clinical outcome.

PMID- 25859455
TI  - Skin and Soft Tissue Infections due to Shewanella algae - An Emerging Pathogen.
AB  - INTRODUCTION: Shewanella spp. are emerging human pathogens, the predominant
      species being Shewanella algae. Shewanella skin and soft tissue infections are
      more commonly seen in immunocompromised patients with a pre-existing cutaneous
      ulcer and most often associated with exposure to marine environments. AIM: The
      study was conducted to investigate the epidemiological and clinical
      characteristics of Shewanella skin and soft tissue infections (SSTIs) for a
      period of five years. MATERIALS AND METHODS: All Gram-negative non-fermenting
      motile isolates which produced pigmented colonies and positive for oxidase and
      H2S were further identified with Vitek 2 system. RESULTS: A total of 16 patients
      with SSTIs due to Shewanella species were identified during the period from 2010
      to 2014. Majority of patients were urban, elderly and fisher men. Shewanella
      algae (n=12, 75%) was the predominant isolate. Skin or mucosal portal of entry
      was found in all patients and seawater contact was recorded in 56.25% of the
      patients. 81% of infections were polymicrobial, common concomitant pathogens
      being gut and marine flora. Peripheral vascular diseases were the predominant
      risk factors with comorbidities like diabetes, hypertension and hepatobiliary
      diseases. Third generation cephalosporins, meropenem and gentamicin were the most
      effective antibiotics while two of the isolates were multidrug resistant. 75% of
      the infected patients recovered completely and three patients died of
      complications. CONCLUSION: Shewanella algae should be considered as an emerging
      pathogen of SSTIs mainly in patients with chronic ulcers and at times be
      multidrug resistant. These infections have a good clinical outcome if prompt
      medical, surgical and supportive treatment is offered.

PMID- 25859456
TI  - To evaluate the different rapid screening tests for diagnosis of leptospirosis.
AB  - INTRODUCTION: Leptospirosis is an acute febrile disease, in tropical and sub
      tropical regions of world. It has been under-reported in India, due to presence
      of non-specific symptoms and unavailability of appropriate laboratory diagnostic
      facilities in most part of the country. The diagnosis of leptospirosis is usually
      based on demonstration of antibodies by different serological tests. AIM: The
      present study aims to evaluate and compare commercially available rapid test.
      DESIGN AND SETTINGS: Case control study. MATERIALS AND METHODS: Three screening
      tests (Leptocheck WB, Latex agglutination test and SD leptospira) were compared
      by using 100 serum samples randomly obtained from clinical cases of Leptospirosis
      admitted in new civil hospital, Surat, Gujarat. All the patients with acute
      Leptospirosis were included in this 4-months pilot study from July 2011 to
      October 2011. All the results were compared with IgM ELISA and MAT for
      confirmation of diagnosis. RESULTS: Leptocheck WB, Latex agglutination test and
      SD leptospira had sensitivities of 84.8%, 84.8% and 72.7% & specificities of
      37.3%, 71.2% and 71.2% respectively as compared to MAT. Leptocheck WB, Latex
      agglutination test and SD leptospira had sensitivities of 90.7%, 89.7% and 53.7%
      & specificities of 93.4%, 90.9% and 60% respectively as compared to IgM ELISA.
      CONCLUSION: Latex agglutination test kit and Leptocheck WB were found to be
      highly sensitive and specific. Neither of these tests require specialized
      equipment, and could be performed in peripheral laboratories with relatively
      little expertise.

PMID- 25859457
TI  - Non traumatic keratitis due to colletotrichum coccodes: a case report.
AB  - Colletotrichum species, a rare and emerging fungus is a well- known plant
      pathogen and an uncommon cause of human infection. It has been implicated as the
      etiological agent of cutaneous phaeohyphomycosis and keratitis, particularly
      following colonization of traumatized tissues or in immunocompromised patients.
      However, it has hardly ever been reported in the absence of such predisposing
      risk factors. Here, we report a case of keratitis with Colletotrichum coccodes
      occurring in a middle- aged, immunocompetent person without any history of trauma
      or co-morbidity. The isolate was sensitive to Amphotericin B and Voriconazole,
      and accordingly the patient was treated successfully with ocular administration
      of Amphotericin B. 

PMID- 25859458
TI  - Spontaneous Bacterial Peritonitis (SBP) caused by Bacillus Cereus in an Alcoholic
      Patient: Case Report and Review of Literature.
AB  - Spontaneous bacterial peritonitis (SBP) is infection of peritoneal covering of
      the abdomen caused by bacteria, without any known etiology. Common known
      predisposing factors are cirrhosis of liver and old age among others. Bacillus
      cereus is an uncommon cause of SBP and often wrongly interpreted as a
      contaminant. We hereby report a case of peritonitis in chronic alcoholic, elderly
      male patient presenting in the outpatient department. Bacillus cereus is often
      regarded as contaminant but must be carefully identified and correlated
      clinically in case of isolation from peritoneal fluid. 

PMID- 25859459
TI  - Schistosome infections: an Indian perspective.
AB  - Schistosomiasis is an endemic helminthic disease of human. Schistosomes display
      considerable biodiversity in habitat, host range, and epidemiology globally. In
      spite of the noticeable presence of sero-positivity for schistosomal antibody and
      passage of schistosome eggs in human faeces, Indian subcontinent has always been
      considered as a low risk region for human schistosomiasis. Several species has
      been described in India which may have association with human infection and
      cercarial rash. Although sporadic cases are not uncommon, the status of human
      schistosomiasis in India is not well investigated. In this review different
      aspect of schistosomal infection in human in India has been described briefly. 

PMID- 25859460
TI  - XIAP and Ki-67: A Correlation Between Antiapoptotic and Proliferative Marker
      Expression in Benign and Malignant Tumours of Salivary Gland: An
      Immunohistochemical Study.
AB  - BACKGROUND: Impaired balance between cell proliferation and apoptosis is crucial
      to the development of malignant neoplasm. The purpose of this study was to
      evaluate and compare the expression of X-Linked inhibitor of apoptotic protein
      (XIAP) (antiapoptotic marker) and Ki-67 (proliferative marker) expression in
      benign and malignant salivary gland (SG) tumours. MATERIALS AND METHODS: The
      study consisted of 40 cases of benign SG tumours and 50 cases of malignant SG
      tumours. The immunohistochemistry was carried out by using Ki-67 antibody (clone
      MIB-1) and XIAP antibody in all the groups. RESULTS: XIAP expression was
      significantly higher in malignant SG tumours than benign SG tumours (p = 0.016).
      Ki-67 LI was significantly higher in malignant SG tumours than benign SG tumours
      (p = 0.0002). Statistically significant positive correlation between Ki-67 count
      and XIAP expression was noted in benign and malignant SG tumours (p = 0.000).
      CONCLUSION: As the expression of an antiapoptotic marker (XIAP) increases, the
      expression of a proliferative marker (Ki-67) also increases from benign to
      malignant SG tumours. Thus, targeted therapy of XIAP may play a future role in
      the management of SG malignancy.

PMID- 25859461
TI  - Autoimmune pancreatitis - a case report.
AB  - Autoiommune pancreatitis (AIP) is a rare disease that has distinct histological,
      immunological, serological and radiological findings. It is characterised
      histologically by lymphoplasmacytic infiltrate, storiform fibrosis, obliterative
      phelibitis and presence of IgG4 positive plasma cells and lymphocytes. Elevated
      serum levels of IgG4 are also noted. It is usually misdiagnosed preoperatively as
      pancreatic cancer. It may involve extrapancreatic sites also and responds well to
      steroid therapy. Here, we share our experience of AIP in a 52-year-old male. 

PMID- 25859462
TI  - Jejunal diverticulosis with perforation - a challenging differential diagnosis of
      acute abdomen: case report.
AB  - Multiple diverticulosis of the jejunum represents a very rare entity. Jejunal
      diverticula are found to be the rarest of all small bowel diverticula. The
      disease is usually asymptomatic and often becomes clinically relevant when
      complicated. This rarity makes it a difficult differential diagnosis. Related
      complications such as diverticulitis, perforation, and bleeding and/or intestinal
      obstruction appear in about 10-30% of the patients which increase the morbidity
      and mortality rates in such individuals. Here, we present a case of jejunal
      diverticulosis with perforation who presented with symptoms of acute abdominal
      pain, vomiting and fever along with a brief review of literature. 

PMID- 25859463
TI  - Adenosquamous variant of metaplastic carcinoma of breast - an unusual
      histological variant.
AB  - Metaplastic carcinoma of breast refers to a heterogeneous group of neoplasms
      characterized by intimate admixture of adenocarcinoma with dominant areas of
      spindle cell, squamous cell and/ or mesenchymal differentiation. They constitute
      the rarest histological variant of invasive ductal carcinoma. These carcinomas
      have aggressive clinical behaviour and show suboptimal response to standard
      treatment. A 49-year-old female presented with lump in the left breast for one
      year. She was diagnosed as infiltrating ductal carcinoma breast with triple
      negative hormone status by trucut biopsy. She completed four cycles of
      neoadjuvant chemotherapy. Postchemotherapy, axillary nodes decreased in size but
      the size of the primary tumour remained the same. Hence, she underwent modified
      radical mastectomy and the specimen sent for histopathological examination.
      Grossly, there was a solitary cyst measuring 4x3cm. Histologically, cyst
      enclosing malignant cells which resemble mature squamous epithelial cells. Also,
      seen are malignant cells in glandular pattern. 

PMID- 25859464
TI  - Asymptomatic cervical mature teratoma in a child: an unusual presentation.

PMID- 25859465
TI  - Prescribing Patterns of Drugs in Acute Respiratory Distress Syndrome (ARDS): An
      Observational Study.
AB  - INTRODUCTION: Acute respiratory distress syndrome (ARDS) is characterized by
      acute respiratory failure and is associated with wide range of clinical
      disorders. Controversy prevails over the pharmacological intervention in this
      disease. The aim of the study was to observe the prescribing pattern of drugs in
      patients with ARDS managed at a tertiary care hospital. MATERIALS AND METHODS:
      This observational study was conducted at tertiary care hospital in India. Data
      of patients admitted from January 2010 to December 2012 was collected. Patients
      aged more than 18 years admitted in ICU, who were diagnosed to have ARDS during
      the study period, were included. A total of 150 patients of ARDS were selected.
      Data was collected as per the pre designed proforma and it included patients'
      age, gender, clinical disorders precipitating ARDS, prescribing pattern of drugs
      and outcome. The data of the subjects was collected till discharge from hospital
      or death. RESULTS: Infection was the cause of ARDS in 81.3% (n=122) of subjects.
      Antibiotics were prescribed in all the subjects and beta-lactams were prescribed
      in 97.3% (n=146). 41.3% (n=62) were prescribed corticosteroids, 39.3% (n=59)
      diuretics and 89.3% (n=134) intravenous fluids. CONCLUSION: The outcome of
      patients on different pharmacological treatment did not show any statistically
      significant difference.

PMID- 25859466
TI  - Reserve drug indent form and its impact on antimicrobial consumption and
      sensitivity pattern in the medical intensive care unit of a tertiary care
      hospital.
AB  - OBJECTIVES: A world without effective antibiotics is a terrifying but a real
      prospect. Overuse or misuse especially of newer and higher antimicrobials (AM) is
      of particular concern, as this contributes to development of resistance among
      microorganisms. To check this trend, the Reserve Drug Indent Form (RDIF) was
      introduced in our hospital and its impact on AM consumption, cost of therapy and
      the sensitivity pattern was studied in the medical intensive care unit (MICU).
      MATERIALS AND METHODS: A retrospective descriptive study in the medical ICU of a
      tertiary care hospital from July 2012 to August 2013. From March 2013, RDIF was
      made mandatory to be filled up prior to prescribing reserve antimicrobials. AM
      consumption (expressed as DDD/100 bed days) and sensitivity pattern (expressed in
      percentage) six months prior to and six months after implementation of the form
      were analysed. RESULTS: The total Reserve AM consumption was 125.79 per 100 bed
      days during the study period. Average occupancy index was 0.50 and length of ICU
      stay was 6 days. The total consumption reduced from 85.55/100 to 40.24/100 bed
      days after the introduction of the RDIF. However, Imipenem usage increased from
      11.35/100 to 23.94/100 bed days, which can be attributed to sensitivity profile
      to Imipenem (82.1%) compared to Meropenem (65.7%). Cost of therapy reduced from
      Rs 6,27,951 to 4,20,469. CONCLUSION: Reserve AM consumption showed a declining
      trend after introduction of the RDIF. Hence, the RDIF served as an important tool
      to combat inappropriate use, reducing the cost burden and also helped to improve
      the sensitivity to reserve drugs.

PMID- 25859467
TI  - Evaluation of potential drug - drug interactions in general medicine ward of
      teaching hospital in southern India.
AB  - BACKGROUND: Polypharmacy is considered as one of the major risk factors in
      precipitation of drug-drug interactions (DDIs). Patient population at high risk
      include the elderly and patients with co morbidities as they are usually
      prescribed with more number of drugs. Critical evaluation of such prescriptions
      by pharmacist could result in identification and reduction of such problems.
      OBJECTIVE: The study aims to assess the prevalence, severity and significance of
      potential DDI (pDDI) in general medicine wards of South Indian tertiary care
      teaching hospital. MATERIALS AND METHOD: A prospective observational study was
      conducted in a general medicine ward for a period of six months (September 2012
      to February 2013). The socio-demographic, clinical characteristics and medication
      prescribed was documented in a specially designed form. Analysis was carried out
      to assess the prevalence, severity and significance of identified pDDIs using
      Micromedex. Descriptive and Univariate analysis were used to report the findings.
      RESULTS: A total of 404 case records reviewed, 78 (19.3%) patients had pDDIs. A
      total of 139 (34.4%) pDDIs were reported during the study period. Majority
      (53.95%, n=75) of the interactions were moderate in intensity and significant in
      nature (53.23%, n=74). Positive association between number of pDDIs and age was
      observed. CONCLUSION: The prevalence of pDDIs was 19.3% which is lesser then
      previously reported studies from India. Patient with more co-morbidities and
      elders were observed with more pDDIs. The study highlighted the need to
      effectively monitor and patients prevent pDDIs to improve patient safety.

PMID- 25859468
TI  - Cycloserine Induced Late Onset Psychosis and Ethambutol Induced Peripheral
      Neuropathy Associated with MDR-TB Treatment in an Indian Patient- A Rare Case
      Report.
AB  - Adverse reactions and toxicity inevitably accompany all treatment courses for
      drug-resistant TB. Our case underscores the importance of awareness regarding
      neuropsychiatric adverse reactions due to MDR-TB therapy and reversible nature of
      it. Cycloserine induced psychosis is most life threatening complication and
      sometimes could be fatal. A 42-year-old male on MDR-TB therapy got admitted for
      his persistent psychotic complaints like hallucinations, delusions and suicidal
      ideations, despite being treated with quetiapine/olanzapine. Eventually patient
      was rehabilitated, cycloserine was stopped and psychotic events regressed slowly.
      Other culprit drugs like ethambutol and levofloxacin causing psychosis was ruled
      out because there was no relapse of psychotic events despite being continued with
      these drugs. He also complained of tingling, numbness, swaying, pain and
      weakness. On examination, he had distal motor weakness in lower limbs, tandem
      gait positive, altered position sense, and tenderness over toes and positive
      Romberg's sign with ataxia. He was diagnosed to have drug induced sensorimotor
      peripheral neuropathy. All these symptoms persisted after stopping cycloserine
      and patient continued to have neuropathy with ethambutol and ethionamide.
      Considering the nature of neuropathy which was mild, mixed sensorimotor and
      resolved completely after 2-3 weeks of stopping, it was more in favour of
      ethambutol. However, we could not rule out the possibility of ethionamide or
      (ethionamide + ethambutol) causing neuropathy or both could have accelerated the
      neurotoxic effects of cycloserine which remained elusive. 

PMID- 25859470
TI  - Study of morbidity profile of a rural population in Tamil Nadu.
AB  - OBJECTIVE: To identify the reported morbidity profile of people according to age,
      gender and organ system affected using International Classification of Diseases
      (ICD) coding, in a demographically defined area in Tamil Nadu in order to
      identify their health care needs and to plan appropriate interventions
      strategies. MATERIALS AND METHODS: This is a-cross sectional study using a
      convenience sample of 12308 persons sceened from the 41 panchayat units of the
      Kattankulathur block, comprising 90 villages with a population of about 2,00,890,
      over a period of one year. Diagnosis made were coded using ICD 10 version and
      data collected was analysed by appropriate statistical methods to explain the
      distribution of morbidity profile among the study population. RESULT: Out of
      total, 38.1% screened were males and 61.9% were females. Underfives were 5.3%,
      school going children 43.3%, adults 39.2% and elderly 12.3%. Majority had illness
      affecting respiratory system (20%), 'symptoms and signs' (19%), musculo-skeletal
      system (16.1%) and digestive system(11.9%). 'Symptoms and signs' classification,
      is a group of conditions which is of nonspecific diseases, signs, symptoms,
      abnormal findings and complaints, apart from the system specific conditions
      diagnosed properly and not elsewhere classified, More males were affeced with
      respiratory, digestive and illnesses with 'symptoms and signs' while more women
      were affected with musculo-skeletal problems. Only 9.7 % of patients reported
      with non-communicable diseases. Among them, 55 % women and 42.3 % men had
      osteoarthritis and 15.7 % women and 21.3 % men had cataract. About 15.8 % women
      and 18.1 % men had hypertension and other heart diseases while 9.7 % women and
      8.4 % men had diabetes and 10.0 % men and 3.9 % women had chronic respiratory
      diseases. CONCLUSION: School going children and adults have higher levels of
      morbidity when compared to elderly and under five children. More females reported
      with illness but morbidity was found to be higher among males. The burden of
      illness increased with age. Acute ailments were responsible for high morbidity
      among children, while chronic ailments caused high morbidity among the elderly.

PMID- 25859469
TI  - Status of eye donation awareness and its associated factors among adults in rural
      pondicherry.
AB  - INTRODUCTION: The value of anything is realized only when it is lost, one such
      thing is vision. Though all the causes of blindness can't be cured, corneal
      blindness can be reverted by corneal transplantation, for which a suitable donor
      cornea is required at right time. There is lack of awareness about eye donation
      among general population, so practice of eye donation is also lacking. Studies
      about awareness of eye donation among general population are lacking in rural
      India, keeping this in mind, present study was conducted. AIM: To determine the
      awareness about eye donation and its associated factors among adults in rural
      Pondicherry, India. MATERIALS AND METHODS: A cross-sectional study was conducted
      at Rural Health and Training Centre (RHTC) of Community Medicine department.
      Total 196 adults visiting to RHTC were interviewed after obtaining informed
      written consent. Data were collected by investigator using pre-designed and pre
      tested questionnaire in local language (Tamil). The data were analyzed using epi
      info 7 software. Chi-square test was used for statistical significance between
      awareness and socio-demographic factors like age, sex, education, occupation,
      etc. Ethical permission was obtained before conducting the study. RESULT: Of 196
      participants, 80.6% subjects were aware about eye donation. Education and
      occupation had significant association with awareness. Main source of information
      about eye donation was television (65.2%). The employed persons had significantly
      more awareness about the correct timing to donate eyes. Education and occupation
      were found to be the predictors for awareness about eye donation. CONCLUSION:
      Although the awareness is good in this population, the quantum of people pledged
      is very low. To make the dream of converting the awareness into pledging and
      procurement of eyes, the knowledge about eye donation is highly required.

PMID- 25859471
TI  - Strategy to Increase Awareness and Involvement of Private Medical Practitioners
      in RNTCP in Taluka Rahata of District Ahmednagar.
AB  - BACKGROUND: The global annual incidence of Tuberculosis (TB) is 9 million cases
      of which estimated 2.3 million cases occur in India. In many parts of India, the
      private sector has remained alienated from Directly Observed Treatment Short
      course (DOTS) implementation; hence, case detection has remained low. The
      performance of Taluka Rahata in terms of TB control was poorest before the year
      2000; RNTCP was started in Taluka Rahata on 24th March 2001. From 2001-2010,
      there was improvement in the performance but was not satisfactory. Hence, present
      study is an attempt to devise strategy, to increase awareness and involvement of
      private practitioners in Revised National TB Control Programme in a rural area of
      Rahata Taluka. AIM: To adopt strategies to improve the awareness and increase
      involvement of Private Practitioners about RNTCP in Rahata Taluka of Ahmednagar
      district. SETTING & DESIGN: It is an Interventional study conducted in Rahata
      Taluka of District Ahmednagar from June to November by giving personal visits to
      all the Private Medical Practitioners of Rahata Taluka at their workplace.
      MATERIALS AND METHODS: Personal visit was given to 143 private medical
      practitioners at their workplace. Workshop used as the major strategy was
      arranged as per RNTCP guidelines. Health education material was distributed.
      RESULTS: Out of the 148 PMPs, 143 could be covered by giving personal visits to
      their clinic for pre-interventional assessment.110 (76.93%) were males while 33
      (23.07%) were females. The mean age of PMPs was 41.60 y. Around 60 percentages of
      PMPs were non- allopathic practitioners. Sensitization workshop was attended by
      132 PMPs. Though no significant difference was observed in their assessment
      regarding etiology about TB, a significant and highly significant value was
      obtained after assessing their KAP regarding their diagnosis & referral for
      sputum diagnosis, categorization and treatment, DOTS provider and TB case
      management. CONCLUSION: The PMPs due to its non-involvement and non-reinforcement
      are lagging with the update knowledge. The PMPs who have attained their higher
      qualification before implementation of RNTCP (before year 2001) are in majority
      unaware of RNTCP Recommendations: Public-Private partnership involving PMPs &
      private hospitals need to be strengthened by additional inputs in the form of
      incentives, free IEC materials and periodic modular training in RNTCP.

PMID- 25859472
TI  - Ghrelin O Acyl Transferase (GOAT) as a Novel Metabolic Regulatory Enzyme.
AB  - BACKGROUND: Obesity and Type 2 Diabetes Mellitus (T2DM) presents a growing threat
      to the global health. Evidences highlight an important role of ghrelin as a key
      regulator of glucose metabolism. The physiological functions of ghrelin are
      mediated by enzyme ghrelin-O-acyltransferase (GOAT) which is capable of
      generating the active form of this metabolic hormone. However, its exact
      mechanism of action and influence on energy balance and glucose metabolism is yet
      to be explored. OBJECTIVES: To review the physiological role of GOAT in the
      regulation of energy balance and glucose metabolism and explore the potential
      therapeutic avenues of modulators of GOAT to counter the progression of obesity
      and T2DM. METHODS: Publications were sought through electronic searches. The
      bibliographies of all papers, book, chapters and editorials were scanned and hand
      searches were also conducted for journals, and conference proceedings.
      CONCLUSION: GOAT peptide modulates the insulin secretion as well as insulin
      sensitivity. Modulators of GOAT signaling like inhibitors of GOAT increases
      insulin secretion, enhance peripheral insulin sensitivity and thus counters
      obesity and T2DM. Modulators of GOAT can be a probable therapy for modifying food
      intake and for countering obesity and T2DM.

PMID- 25859473
TI  - mHealth in the Prevention and Control of Non-Communicable Diseases in India:
      Current Possibilities and the Way Forward.
AB  - Mobile health technology has been used effectively for healthcare delivery in
      many developing countries. India is currently facing an epidemic of Non
      Communicable Diseases (NCDs). With greater availability of cheaper phones in the
      market, the user base of mobile phones in India is increasing rapidly. The
      present review was thus conducted to explore the current possibilities and future
      scope of mobile health for NCD prevention and control in India. Literature search
      was conducted using MEDLINE, EMBASE, and Cochrane Library to collect information
      regarding mobile health interventions. Two authors extracted the data and
      included studies if at least the abstract was available. Information from key
      reports and government websites were also included. We examined information from
      domains such as need for mobile health in NCDs in India, and the advantages,
      scope and challenges of mobile health for healthcare delivery in India. Existing
      mobile health systems in India, current evidence of mobile health use in NCDs,
      and the recent mobile health related initiatives taken by Government of India
      were also assessed. Though we found some examples of current mobile phone usage
      in many health related programmes in India, data from mobile health research is
      scarce, particularly for NCDs. The current evidence base needs to be
      strengthened. There is also a need for identifying various opportunities in the
      recent initiatives taken by Government of India. It can be concluded that though
      mobile health has many advantages, there are numerous challenges which need to be
      addressed before scaling it up at the national level. 

PMID- 25859474
TI  - Cruciate incision for treatment of primary/recurrent cases of seroma/hematoma of
      pinna : a novel approach.
AB  - INTRODUCTION: Seroma of pinna have a high predisposition for recurrence. Its
      surgical management requires excision of cartilage and perichondrium which can
      cause scarring, deformity of pinna, perichondritis and abscess formation,
      postoperatively.The aim of the current study is to the access the outcome of a
      novel approach using cruciate incision for surgical treatment of seroma/ hematoma
      of pinna. MATERIALS AND METHODS: Study was conducted at Father Muller Medical
      College in the Department of Otorhinolaryngology for a period of three months
      between January 2014 to March 2014 during which period 30 patients with seroma of
      the pinna were taken up for the study. Procedure was done under local anaesthesia
      with all aseptic precautions. A cruciate incision was given over the most
      dependent part of the swelling and flaps were raised. The collection was drained
      and the under surface of the flap was scraped using Rosen's knife followed by
      pressure dressing for three days. Patients were followed up for three months.
      RESULTS: A total of 30 patients with seroma were studied. Out of the 30 cases 24
      were primary cases and 6 were recurrent cases. Majority of the patients were in
      the age group 41-50 y. Out of 30 patients 18 were males and 12 were females. Out
      of 30 patients studied, none of them had recurrence. Four patients however
      developed perichondrial reaction with pain and inflammation which required
      analgesics and antibiotics. In 6 cases a thickening of the auricle at the site of
      incision was noticed which resolved over a period of 4 to 5 months. Overall
      cosmetic deformity was negligible with most of the patients showing a negligible
      scar after 6 months of follow up. CONCLUSION: Cruciate incision is a good
      technique for treatment of seroma and hematoma of pinna as the outcome is good
      with no recurrence.

PMID- 25859475
TI  - Tuberculosis of Waldeyer's Ring with an Atypical Presentation as Chronic Adeno
      Tonsilitis.
AB  - Primary tuberculosis of the oropharynx and nasopharynx is a rare clinical
      entity.It usually arises secondary to pulmonary tuberculosis. We report a rare
      case of a 20-year-female, who presented with fever and throat pain. Examination
      revealed hypertrophied adenoids and tonsils, which was ultimately proved as
      tuberculosis.Enlargement of the palatine tonsils could be due to a multitude of
      causes, and a thorough evaluation is necessary to arrive at the right
      diagnosis.Increased awareness of nasopharyngeal and oropharyngeal tuberculosis is
      important in tropical countries, as the disease may be overlooked resulting in
      inappropriate management. 

PMID- 25859476
TI  - Optical coherence tomography assisted retinal nerve fibre layer thickness profile
      in high myopia.
AB  - INTRODUCTION: To evaluate the association of high myopia with retinal nerve fibre
      layer (RNFL) thickness by Fourier domain optical coherence tomography (FD OCT).
      MATERIALS AND METHODS: Fifty highly myopic eyes (25 patients) and forty
      emmetropic eyes (20 Normal subject) were randomly selected after excluding
      concomitant ophthalmic disorder and RNFL thickness measured using the Fourier
      domain optical coherence tomography (FD OCT). RESULTS: The overall mean RNFL
      thickness in the myopic groups and control were 87.89 MUm and 111.64 MUm
      respectively. The mean retinal nerve fibre thickness was significantly less in
      myopic eyes as compared to control group (p =0.0001). Retinal nerve fibre layer
      thickness shows topographic double hump pattern in both the groups (myopes and
      emmetropes). CONCLUSION: Retinal nerve fibre thickness was significantly less in
      myopic eyes as compared to emmetropic eyes. The retinal nerve fibre layer
      thinning in high myopes may be confused with open angle glaucoma, a disease also
      prevalent in high myopes. There is therefore a need to have retinal nerve fibre
      layer thickness normogram for high myopes of a given population group to avoid
      wrong interpretation.

PMID- 25859477
TI  - Effect of insulin resistance in assessing the clinical outcome of clinical and
      subclinical hypothyroid patients.
AB  - BACKGROUND: The effect of thyroid status on insulin sensitivity is of great
      interest but despite various studies there is conflicting data on this subject.
      Hypothyroidism has been associated with disorders of glucose and insulin
      metabolism involving defective insulin secretion in response to glucose,
      hyperinsulinemia, altered peripheral glucose disposal and insulin resistance.
      Thyroid dysfunction leads to alterations in glucose and lipid metabolism which is
      an important risk factor for cardiovascular diseases. The dyslipidemia and
      insulin resistance should be managed aggressively to reduce the impending risk.
      OBJECTIVES: The prime objectives of the study were as follows: 1. To compare and
      correlate insulin resistance levels with T3, T4, and TSH in hypothyroidism
      patients. 2. To compare and correlate lipid profile with T3, T4, and TSH in
      hypothyroidism patients with healthy controls. MATERIALS AND METHODS: Forty
      hypothyroidism patients and Forty healthy age and sex matched controls in the age
      group of 18 to 45 years were taken for the study. The venous blood samples
      collected were used for estimation of thyroid hormones, insulin, glucose and
      lipid profile. RESULTS AND DISCUSSION: There is significant increase in insulin,
      Homa-IR and glucose levels in hypothyroidism cases when compared to controls.
      Cholesterol, LDL, VLDL and triglycerides were significantly increased, whereas
      HDL was significantly decreased in hypothyroidism cases when compared with
      controls. Insulin was moderately correlated with cholesterol but there was no
      correlation with other lipid profile parameters in hypothyroidism patients. Homa
      IR was significantly correlated with TSH in hypothyroidism cases when compared
      with controls. TSH was significantly correlated with cholesterol and LDL in
      hypothyroidism cases (both clinical and subclinical) when compared with controls.
      The present study helps to evaluate changes in insulin resistance and lipid risk
      factors. These factors should be managed aggressively to reduce the impending
      risk of cardiovascular diseases.

PMID- 25859478
TI  - Evaluation of clinical outcomes in patients undergoing dual vessel percutaneous
      coronary intervention using sirolimus-eluting coronary stent system in India.
AB  - INTRODUCTION: Coronary artery disease is the most common catastrophic disease in
      India. The safety and effectiveness of dual vessel sirolimus-eluting stent (SES)
      implantation (used as an intervention in CAD) is currently unknown in Indian
      population. The purpose of this study was to investigate one year clinical
      outcomes of patients with dual vessel coronary artery disease after implantation
      of the Supralimus-Core SES, in a "real-world" setting. MATERIALS AND METHODS: We
      evaluated 60 patients between April-2011 and August-2012, who underwent dual
      vessel percutaneous coronary intervention (PCI) with the Supralimus-Core SES
      implantation at the same index procedure. Dual vessels were defined as
      involvement of two major epicardial vessels (right, left anterior descending,
      circumflex, or left main coronary arteries) or one major epicardial vessel and a
      branch (>=2.5 mm in diameter) originating from another major epicardial vessel.
      The primary endpoint was target lesion failure (TLF) defined as the composite of
      cardiac death, myocardial infarction (MI), and clinically-driven target lesion
      revascularization (TLR) at one year. Secondary endpoint included combined
      (definite, probable and possible) stent thrombosis (ST). RESULTS: A total of 120
      lesions were treated in 60 enrolled patients (mean age 56.0+/-9.2 y; 80.0% male)
      with average stent length of 23.1+/-8.5 mm. Among 60 patients, diabetes,
      hypertension and hypercholesterolemia were present in 15 (25.0%), 22 (36.7%) and
      25 (41.7%) patients respectively. Indications for PCI were unstable angina in 30
      (50.0%) patients and stable angina in 11 (18.3%) patients. Overall, 40 (33.3%)
      lesions were classified as complex (American College of Cardiology/American Heart
      Association type B2/C). The cumulative TLF rate was 5.0% (n=3) at one year.
      Cardiac death, MI and clinically-driven TLR occurred in 1 (1.7%), 0 (0%) and 2
      (3.3%) patients, respectively at one year follow-up. The Kaplan-Meier curve of
      the freedom from overall events at one year was 95.0%. According to the Academic
      Research Consortium definition, there were no events of stent thrombosis during
      one year. CONCLUSION: Our study shows that, dual vessel Supralimus-Core SES
      implantation allows safe and effective treatment with low rates of TLF at one
      year follow-up in Indian population.

PMID- 25859479
TI  - The Study of Efficacy, Tolerability and Safety of Theophylline Given Along with
      Formoterol Plus Budesonide in COPD.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a common disease
      causing significant socioeconomic burden. COPD patients, commonly smokers develop
      resistance to inhaled steroids attributed to deficiency of histone deacetylase 2
      (HDAC2). The study of relationship between systemic inflammation and functional
      performance demonstrated that increased CRP level is inversely related to six
      minute walk distance (SMWD) and Forced Expired Volume in one second (FEV1).
      Theophylline restores HDAC2 activity thereby unlocking steroid resistance and
      potentiating inhaled corticosteroids (ICS) action culminating in reduced airway
      inflammation and mortality. AIM: To study the effects of addition of Theophylline
      to the combination of Formoterol plus Budesonide on various objective and
      subjective parameters in moderate to severe COPD patients and to assess the
      safety profile of the combination. Setting and Study design: A single blinded,
      prospective, randomized, placebo controlled study at a tertiary care hospital in
      Jaipur, India. MATERIALS AND METHODS: Fifty eight patients diagnosed with
      moderate to severe COPD were randomized into two groups. Group A patients
      received Formoterol 24MUg plus budesonide 800MUg daily in divided doses along
      with Theophylline while group B patients received Formoterol 24MUg plus
      budesonide 800MUg daily in divided doses along with placebo tablets. Both groups
      were followed up on 15th, 30th &60th day. During every visit all patients were
      assessed subjectively (symptom scoring) and objectively (spirometry, CRP, SMWT)
      and adverse effects if any were recorded. The obtained data subject to
      statistical analysis using"Graph pad Instat3" software. RESULTS: Statistically
      significant improvement with a decline in total symptom score (p < 0.0001) was
      found with respect to "Night symptoms"&"SOB on rising" in group A. Theophylline
      group showed significant improvement in SMWD and FEV1.Mean fall in CRP was
      greater in Group A (not statistically significant). No side effects requiring
      withdrawal of drug were noted with Theophylline. CONCLUSION: Addition of
      Theophylline to Formoterol plus Budesonide reduces dyspnea, improves exercise
      performance and pulmonary functions in moderate to severe COPD. Further studies
      are required to explore if reduced dosage would have equal efficacy with better
      safety and tolerability profile.

PMID- 25859480
TI  - Combination Versus Monotherapy for the Treatment of HIV Associated Cryptococcal
      Meningitis.
AB  - OBJECTIVE: To study the efficacy of anti Cryptococcal treatment by cerebrospinal
      fluid (CSF) fungal negativity after two weeks of treatment with amphotericin B
      alone or combined with fluconazole in treatment of HIV associated Cryptococcal
      meningitis (CM). MATERIALS AND METHODS: A total of 84 human immunodeficiency
      virus (HIV) associated CM patients confirmed by CSF culture positivity were
      recruited for the study. Patients were randomly divided into two groups. Group A
      was given amphotericin B alone whereas Amphotericin B in combination with
      fluconazole was given in group B for the treatment of CM. Patients were followed
      for 14 days. RESULTS: Maximum number of patients was in the age group 21-49 y.
      All the 84 patients had <100 CD4 counts/MUl. After 14 days of the treatment in
      group A and B, there was no significant difference in terms of fever, headache
      and neck stiffness as a clinical outcome. But in group B there was improved in
      altered sensorium and focal neurological deficit as compared to group A. After 14
      days of the treatment CSF culture negativity was more in group B as compared to
      group A. CONCLUSION: Amphotericin B in combination with fluconazole is
      recommended for the treatment of HIV associated CM.

PMID- 25859481
TI  - Type 1 and type 3 Gaucher disease in two siblings in a family: 2 unusual case
      reports.
AB  - Gaucher disease (GD) is an autosomal recessive disorder, characterized by lack of
      acid beta-glucosidase (glucocerebrosidase) enzyme resulting in accumulation of
      glucosylceramide in different organs. It is common in Ashkenazi Jews but rare in
      India. Around five hundred cases are identified and diagnosed in India. We are
      reporting two interesting cases of type 1 non-neuropathic and type 3 juvenile
      subacute neuropathic variant of adult Gaucher disease in two of three siblings in
      a family. 

PMID- 25859482
TI  - Cirrhosis: an unusual presentation of sickle cell disease.
AB  - Hepatobiliary complications of sickle cell disease are relatively rare but well
      recognised in literature. Clinical syndromes range from mild intrahepatic
      cholestasis and gallstones to life threatening sequestration crisis. Most
      patients, homozygous for sickle cell anaemia, present before adolescence. We
      report a case of an adult man with no prior symptoms who presented for the first
      time with decompensated cirrhosis, which was found to be due to underlying
      previously unrecognised sickle cell anaemia. 

PMID- 25859483
TI  - Normokalemic thyrotoxic periodic paralysis with preserved reflexes- a unique case
      report.
AB  - Although serum potassium levels are usually subnormal in Thyrotoxic Periodic
      Paralysis (TPP), but in exceptionally rare circumstances, it may be normal
      leading to the entity called normokalemic TPP. The diagnosis of normokalemic TPP
      is more often overlooked and/or delayed due to lack of awareness among the
      physicians and associated mild symptoms of hyperthyroidism. Here, the author
      describes the case of a 27-year-old male with newly diagnosed but untreated
      Grave's disease and TPP who was normokalemic during the acute phase of paralysis.
      Hypokalemia was documented only after resolution of paralytic attacks during
      subsequent days of admission. The importance of the case report is to highlight
      upon the fact that TPP should always be considered in an "previously
      asymptomatic" young Asian individual with acute paralysis with or without
      hypokalemia , and thyroid function and serial potassium values should be
      evaluated for diagnosing the usual hypokalemic type or the more rarer variant
      normokalemic TPP. This case report also deserves mention as the patient of TPP
      had a notable feature of having preserved reflexes in the face of hypokalemia. 

PMID- 25859484
TI  - Osteoblastic and osteoclastic metastases in a single vertebra-a rare
      presentation.
AB  - Malignancies may produce bony metastases which may be osteoclastic or
      osteoblastic. Vertebrae are a common site for bony metastases. Prostatic
      adenocarcinoma is an important source of vertebral metastases that are mainly
      osteoblastic in nature. As the osteoblastic metastases are developing there is an
      ongoing osteoclastic activity which is going on at the microscopic level.
      Presence of gross osteoblastic and osteoclastic lesions, in the same vertebra,
      have not been reported at the time of presentation. Here a rare case of vertebral
      metastases is being presented which shows osteoblastic and osteoclastic gross
      lesions in the same vertebra. 

PMID- 25859485
TI  - A rare case of autoimmune hypophysitis presenting as temperature dysregulation.
AB  - Autoimmune hypophysitis is a rare cause of pan-hypopituitarism. Hypothalamic
      involvement in autoimmune hypophysitis is rare and usually manifests as central
      diabetes insipidus due to antibodies against arginine vasopressin. Temperature
      dysregulation is occasionally seen with suprasellar tumours but has never been
      reported with hypophysitis. We report a case of a middle aged man who presented
      to us with the complaints of documented body temperature fluctuations since two
      months followed gradually by hoarseness of voice, sexual dysfunction and syncope.
      Examination was remarkable for postural hypotension, dry coarse skin and delayed
      ankle reflexes. Patient's hormone profile revealed pan-hypopituitarism and
      elevated titre of anti-TPO antibodies. Patient's work up for secondary causes of
      hypopituitarism was negative. MRI brain revealed typical findings of
      hypophysitis. Patient was suspected as a case of autoimmune hypophysitis and was
      immediately treated with prednisolone along with hormone replacement. Rapid
      response within 30 days was observed in the form of subsidence of temperature
      fluctuations, improvement in general well being, sexual function and repeat MRI
      done after one month which revealed a partial empty sella. Autoimmune
      hypophysitis as a potentially treatable cause of temperature dysregulation has
      been highlighted in this case. 

PMID- 25859486
TI  - Embryonic metastatic rhabdomyosarcoma compressing the trachea.

PMID- 25859487
TI  - A comparitive study to evaluate the role of serum lipid levels in aetiology of
      carcinoma breast.
AB  - INTRODUCTION: Breast cancer is the most common occurring cancer in women
      worldwide. Various factors that have lead to change in lifestyle are thought to
      be associated with increase in breast cancer incidence in Asian countries.
      Several clinical studies suggest the prognostic significance of serum lipid
      levels in breast cancer. Present study was planned to confirm the association of
      lipids levels with breast cancer. MATERIALS AND METHODS: Lipid analyses was
      carried out on serum samples from 100 breast cancer patients and 100 control
      women, with a age group of 25 y and above. The case & control group included 50
      premenopausal women and 50 postmenopausal women. RESULTS: Patients of study group
      had high Low density lipoproteins (LDL) (p-value - 0.00), Triglycerides (TG) (p
      value -0.001) and Total cholesterol (TC) (p-value -0.00) as compared to control
      group. There was no association of VLDL (p-value -0.436) and HDL (p-value -0.797)
      among study group and control group. There was no association of lipid levels in
      different grades of carcinoma. CONCLUSION: High levels of LDL, TG and TC were
      associated with breast cancer. However, no association was there in different
      grades of carcinoma. So it may be concluded that, LDL, TG and TC may be having
      some role in aetiology of breast cancer. Therefore, early detection and control
      of these factors may help in reducing the incidence of breast cancer and
      ultimately social and economic burden on society.

PMID- 25859488
TI  - Mucoid cyst of the penis: a case report.
AB  - Penile cysts are rare benign lesions. Their clinical or pathological diagnosis is
      extremely difficult. Less than 200 cases have been reported in literature. Most
      of them are asymptomatic and present since birth, but usually they are only
      detectable in adolescence or adulthood. These lesions rarely interfere with
      sexual function. These cysts most likely arise from ectopic urethral mucosa
      sequestered in the penile skin during embryologic development. We report a rare
      case of a 55-year-old man with a 4.5 * 4 cm nodule on the prepuce (ventral
      surface), which appeared two years ago and interfered with his sexual function.
      The nodule was excised by circumcision and a histopathological examination
      revealed a mucoid cyst of penis with squamous metaplasia. No recurrence was
      observed at a one year follow-up and the patient's sexual function returned to
      normal. 

PMID- 25859489
TI  - Amyand's Hernia: Case Report -Current Dilemma in Diagnosis and Management.
AB  - Amyand's hernia is an extremely rare condition, often misdiagnosed as a
      strangulated inguinal hernia, in which the inguinal hernial sac contains the
      vermiform appendix. It is often a surgical surprise. The reported incidence is
      approximately 1% of all adult inguinal hernia cases. Acute appendicitis in the
      Amyand's hernia is even less common. We report a rare presentation of acute
      appendicitis associated with Amyand's hernia managed by en masse reduction of the
      hernia followed by laparoscopic appendicectomy and open Lichtenstein's tension
      free inguinal hernioplasty. 

PMID- 25859490
TI  - Rhabdoid meningioma: report of two cases.
AB  - Rhabdoid meningioma is an uncommon anaplastic variant of meningioma. We describe
      the clinicoradiological and histomorphological features of two such cases of
      meningioma, with a brief review of literature. One case in a 9-year-old girl,
      presented initially as an atypical meningioma in the right fronto-parietal
      region, which on recurrence 18 months later, evolved into a rhabdoid meningioma.
      The second case in a 33-year-old male was located in the right parieto-occipital
      region. 

PMID- 25859491
TI  - Giant aggressive mesenteric fibromatosis- a case report.
AB  - Fibromatosis are rare, accounting for 0.03% of all tumours. Mesenteric
      fibromatosis is a very rare (8% of all desmoid neoplasm). Aggressive fibromatosis
      of mesentery is a rare surgical problem affecting 2-4 per million people. Females
      are more commonly affected than males (Estrogen acts as a growth factor). It is
      locally invasive and tends to recur but never metastasize. Here, we are
      discussing about 24-year-old male presented with progressive abdomen distension
      associated with pain since one month. Abdominal examination showed a firm non
      tender intra-abdominal mass, measuring around 15x14 cm size, with intrinsic
      mobility, which was perpendicular to mesenteric line, all borders were well-made
      out. CECT abdomen showed features suggestive of GIST . Elective Laparotomy was
      done and a giant mass arising from mesentery without any infiltration to the
      surrounding structures was noted. The entire mass was excised and mesentery
      repaired. Histopathology showed uniform band of spindle shaped cells arranged in
      fascicles admixed with blood vessels in a collagenous stroma.
      Immunohistochemistry showed Beta Catenin +ve, CD 117-ve, CD 34 -ve and SMA-ve,
      which is confirmative of Fibromatosis. Postoperative period was uneventful. 

PMID- 25859492
TI  - Outcome of ovarian drilling in women with polycystic ovary syndrome.
AB  - OBJECTIVE: To determine the effectiveness and safety of laparoscopic ovarian
      drilling (LOD) in inducing ovulation in women with polycystic ovary syndrome
      (PCOS) who failed to conceive after medical methods of ovulation induction.
      MATERIALS AND METHODS: A retrospective study of all women who underwent LOD as a
      treatment for anovulatory infertility between January 2010 and December 2011 was
      conducted. Women diagnosed to have PCOS by the Rotterdam criteria were considered
      for the study. Those who had PCOS but were associated with male factor
      infertility, deep infiltrating endometriosis and submucous fibroids were
      excluded. RESULTS: A total of 43 women underwent LOD during the study period.
      Majority were aged 26 to 30 years and two-thirds were overweight or obese. Most
      (72%) of them had primary infertility. Other factors which could have contributed
      to infertility such as superficial endometriosis, septate uterus and unilateral
      tubal block were observed in 30.2% of the women, which were dealt with
      concomitantly. When we excluded the 14% who were lost to follow up, 23 of 43
      (53.5%) women achieved pregnancy and almost 70% of them did so within the first 6
      months. None of our study population had ovarian hyperstimulation or multiple
      pregnancy. CONCLUSION: LOD thus not only helps in regulating ovulation and
      enhancing conception rates but also provides an opportunity to assess the pelvis
      for other potential causes of subfertility which could be treated at the same
      time. We therefore believe that diagnostic hysteroscopy and laparoscopy should be
      offered quite high-up in the hierarchy of infertility investigations and
      treatment.

PMID- 25859493
TI  - Tetra-phocomelia: the seal limb deformity - a case report.
AB  - We report a case of term live baby with tetra-phocomelia born to a 35-year-old
      G3P2L2A0 with history of consanguineous marriage. She was an unbooked case from a
      tribal community with no previous antenatal visits. At 39 wk of gestation, she
      was admitted to our hospital with complaint of pain abdomen and on examination
      was found to be in second stage of labour. She delivered vaginally a term live
      2.5 kg female baby with multiple anomalies. There was no history of drug intake,
      radiation exposure, maternal diabetes or family history of congenital anomalies
      to support the occurrence of tetra-phocomelia in this baby. The neonate also had
      multiple facial abnormalities like hypertelorism, microretrognathia and partial
      cleft palate. Further investigations revealed no abnormalities of internal
      organs. At present the baby is being followed up at our paediatric department.
      The case is reported owing to its rarity and term live birth. 

PMID- 25859494
TI  - Pregnancy with uterine didelphys with obstructed hemivagina and pyocolpus.

PMID- 25859495
TI  - Infected Gap Non Union of Radius Treated with Modified Nicoll's Technique-A Case
      Report.
AB  - Management of atrophic non union of forearm bones is a challenging task. Various
      methods of treatment available in the literature are cortical tibial graft
      (Boyd), ulnar segment graft (Miller and Phalen), iliac crest graft (Spira),
      cancellous insert graft (Nicoll), vascularized fibular graft (Jupiter), and bone
      transport by ring fixator (Tesworth). We here report a case of infected non union
      of radius managed with modified Nicoll's method. Here, intra medullary nailing is
      preferred over plating which was originally described by Nicoll. At two years
      follow up, the patient is symptom free and is able to carry out his daily
      activities with ease. 

PMID- 25859496
TI  - Neurocysticercosis (NCC) with Hydrocephalus, Optic Atrophy and Vision Loss: A
      Rare Presentation.
AB  - Neurocysticercosis (NCC) is one of the most common parasitic infestations (Taenia
      solium) of central nervous system (CNS) in children. Seizures are the common
      presenting symptoms. Hydrocephalus and optic atrophy are rare complications which
      may require neurosurgical interventions. We report a case of NCC with
      hydrocephalus and bilateral optic atrophy associated with vision loss in a
      Nepalese patient who improved with anti-parasitic therapy followed by ventriculo
      peritoneal (VP) shunting. 

PMID- 25859497
TI  - Disseminated langerhans cell histiocytosis presenting as cholestatic jaundice.
AB  - Langerhans cell histiocytosis (LCH) is a disorder associated with proliferation
      of Langerhans cells in various organs. LCH secondary to multisystem involvement
      can present in a variety of ways. Because of its infiltrative nature, LCH can
      involve the skin, lymph nodes, the lung or the liver. Jaundice in LCH is a
      manifestation of liver disease; biliary dilatation secondary to lithiasis or may
      be due to coexistent Niemann-Pick disease. However, a case of cholestasis has
      been very rarely described. Cholestasis may result from lymph nodes obstructing
      the porta hepatis. In this report, we describe a case of type II histiocytosis X
      with obstructive cholestasis and pulmonary involvement in the form of cysts
      without significant lymphadenopathy at the porta. 

PMID- 25859498
TI  - Incontinentia pigmenti: a rare genodermatosis in a male child.
AB  - Incontinentia pigmenti is rare X-linked dominant disorder. There is no consistent
      expression of Incontinetia pigmenti in female child, but in male child, they
      always lead to death in utero. Vesicular, verrucous, hyperpigmented, and atrophic
      stages are the four stages of Incontinetia Pigmenti and it is uncommon for all
      stages to be seen in a same case. It is a rare genodermatosis, with only very few
      cases of male child with Incontinentia pigmenti have been reported. Thus, we
      report this case due to its extreme rarity and the child showed all the first 3
      stages on followup. 

PMID- 25859499
TI  - Magnetic resonance imaging (MRI) appearances of primary amelanotic malign
      melanoma in the nasal cavity: a rare case.
AB  - Malign melanoma of the nasal cavity that arises at such an unusual location is an
      exceptional case only occasionally mentioned in the literature. An amelanotic
      form, which is an uncommon type for this malignancy, also has an unusual
      radiological appearence from the classic melanotic form. We report here the
      magnetic resonance imaging (MRI) findings of a 46-year-old man who had a nasal
      cavity mass diagnosed as an amelanotic malign melanoma and discuss the importance
      of differential diagnosis with such an unusual radiological manifestation in this
      location. 

PMID- 25859500
TI  - Saccular aortic aneurysm causing hoarseness: an alarming bell..!

PMID- 25859501
TI  - Postpartum Acute Pulmonary Oedema with Sub clinical Rheumatic Heart Disease.
AB  - Acute dyspnea with pulmonary oedema in postpartum is uncommon but life
      threatening event. Contributing factors for pulmonary oedema include,
      administration of tocolytics, underlying cardiac disease, iatrogenic fluid
      overload and preeclampsia acounting 0.08% of pregnancies. Pulmonary embolism,
      amniotic fluid embolism, pneumonia, aspiration and pulmonary oedema are some of
      the potentially devastating conditions that should be considered by the attending
      physician. Here, we report a case of postpartum acute pulmonary oedema referred
      to causality after an emergency caesarean section in a private hospital. No
      matter what the underlying pathology, prompt administration and appropriate
      resuscitation is always the first priority. Only after the patient has been
      stabilized attention must be turned to diagnosis and specific treatment. A
      diagnosis of severe Mitral Stenosis, probably of rheumatic origin was made after
      stabilizing the patient. 

PMID- 25859502
TI  - Local Anaesthetic Systemic Toxicity in a Patient under General Anaesthesia (GA):
      A Diagnostic Challenge.
AB  - Local anaesthetic systemic toxicity (LAST) is one of the most dreadful
      complications after local anaesthetic (LA) use and it is very difficult to
      manage. The diagnosis of LAST is purely clinical and its presentation is usually
      obscured in a sedated or anaesthetized patient. A 25-year-old male patient
      undergoing laparotomy for acute duodenal perforation under general anaesthesia
      developed seizures after epidural administration of 0.5% bupivacaine. All other
      possible causes of seizures were ruled out. Seizures were controlled with
      antiepileptic drugs and patient recovered fully after withholding LA
      administration. Although, lipid rescue is recommended for LAST, our patient was
      managed without its use. We, therefore, recommend that utmost care and vigilance
      should be exercised while using local anesthetics as there is no perfectly
      accurate method to rule out intravascular administration of LA. Even, if LA is
      correctly used, LA is detected in plasma due to its systemic absorption from
      injection site. 

PMID- 25859503
TI  - Eventful anaesthesia: can we prevent it?
AB  - To ensure the utmost safety, it is recommended that prior checking the machine
      and breathing systems as mandatory. Certain factors beyond the control of the
      anaesthesiologist lead to the operative room incidences jeopardizing the
      anaesthetised patient which otherwise cannot be prevented by prior custom
      checking. Delayed occlusion of a spiral reinforced endotracheal tube during prone
      position anaesthesia and faulty dual control knob of fresh gas flow of an
      anaesthesia machine leading to inadequate ventilation are given as examples. In
      above events, a prior checking the machine or tracheal tube, could not prevent
      its occurrence. However, use of a deputy of the objects resulted in uneventful
      anaesthesia. 

PMID- 25859504
TI  - A Case of SSRI Induced Irreversible Parkinsonism.
AB  - Serotonin specific reuptake inhibitors (SSRI) are widely used antidepressants for
      variety of clinical conditions and have found popularity. They are sometimes
      associated with extrapyramidal side effects including Parkinsonism. We report a
      case of generalized anxiety disorder on treatment with SSRI (fluoxetine /
      sertraline) who developed irreversible Parkinsonism. SSRI are known to cause
      reversible or irreversible motor disturbances through pathophysiological changes
      in basal ganglion motor system by altering the dopamine receptors
      postsynaptically. Clinician should keep risk benefit ratio in mind and change of
      antidepressant of different class may be considered. Case is reported to alert
      physicians to possibility of motor system damage while treating with SSRI. 

PMID- 25859505
TI  - Internet sex addiction and its negative consequences: a report.

PMID- 25859506
TI  - Systematised epidermal nevus - a case report.
AB  - A 20-year-old female presented with raised skin lesions all over the body since
      birth. Clinical examination revealed multiple pigmented macules and
      hyperkeratotic papules seen along Blaschko's lines over the face, neck, trunk and
      both lower limbs. Histopathological examination revealed hyperkeratosis with
      moderated acanthosis and uniform pigmentation over basal zone. Systemic
      examination was found to be normal. A diagnosis of systematised epidermal nevus
      in the absence of epidermal nevus syndrome was diagnosed and the patient was
      asked to undergo carbon dioxide laser mediated destruction of the skin lesions.
      The patient was also advised to be under surveillance for late onset neurological
      symptoms. 

PMID- 25859507
TI  - Papulonecrotic tuberculid with scrofuloderma: an uncommon association.
AB  - Cutaneous tuberculosis can be classified as true cutaneous tuberculosis and
      tuberculids which is regarded as a hypersensitivity reaction to M. tuberculosis
      in patients with a high degree of tuberculin sensitivity. Papulonecrotic
      tuberculid (PNT) is a form of tuberculid. It is an uncommon manifestation even in
      areas with high prevalence of tuberculosis. We report a case of 35-year-old man
      who presented with necrotizing papules in symmetrical fashion over the trunk and
      extremities for last one year along with a discharging sinus in right axilla for
      last two months. Papulonecrotic tuberculid (PNT) with scrofuloderma were
      suspected on clinical examination. Mantoux test was strongly positive with
      20x20mm. He was treated successfully with ATT without any further appearance of
      new lesions. 

PMID- 25859508
TI  - Allopurinol induced stevens - johnson syndrome - a case report.

PMID- 25859509
TI  - Anaplastic Thyroid Carcinoma (ATC) with Superior Vena Cava (SVC) Syndrome,
      Cardiac Tamponade and Pleural Effusion: An Unusual Clinical Presentation.
AB  - Superior vena cava (SVC) syndrome and cardiac tamponade are potentially life
      threatening conditions that are not uncommon in the oncological setting but their
      occurrence together in a patient is infrequent. Herein, we present a case of 50
      year-old male who presented with SVC syndrome and pleural effusion; developed
      recurrent cardiac tamponade in the hospital. Fine needle aspiration cytology
      (FNAC) of left supraclavicular lymph node which appeared during hospital stay
      revealed high grade carcinoma and diagnosis of anaplastic thyroid carcinoma was
      established by FNAC of thyroid nodule. Despite rarity, clinicians must be aware
      of such presentation of thyroid malignancy. 

PMID- 25859510
TI  - Metastatic amelanotic melanoma with occult primary masquerading as sarcoma.
AB  - Malignant melanoma with occult primary is extremely rare. It is found that
      survival is almost same or even better than the melanomas with known primary
      site. Surgeons should have a high index of suspicion when a patient presents like
      sarcoma which bleeds profusely when planning for excision. Here, is an unusual
      case of young adult which presented initially with granulomatous lymphandenitis
      in axilla with primary suspicion of tuberculosis, later turning out to be sarcoma
      on FNAC and MRI. On immunochemistry (IHC), the final diagnosis of amelanotic
      melanoma was made and further workup did not show up any primary site of origin. 

PMID- 25859512
TI  - Non-functional paraganglioma of retroperitoneum mimicking pancreatic mass with
      concurrent urinary bladder paraganglioma: an extremely rare entity.
AB  - Paragangliomas are extra-adrenal tumours of the autonomic nervous system, which
      rarely present as primary retroperitoneal mass mimicking pancreatic malignancy
      (incidence 2-8 per million populations). Urinary Bladder Paraganglioma are also
      extremely rare (0.06% of all Bladder Tumour and 6% of Paragangliomas) with most
      being malignant and high grade tumours. Non-functional varieties of both tumours
      are usually incidentally diagnosed. The possibility for malignant transformation
      in them makes surgical excision the treatment of choice. A 45-year-old lady with
      abdominal pain was investigated to have a complex retroperitoneal mass behind
      head of pancreas and a urinary bladder mass. Complete excision of retroperitoneal
      and bladder lesion was done. Histopathological examinations of both specimens
      were suggestive of Paraganglioma with no abnormal mitotic activity and
      capsular/vascular invasion. Although concurrent non functional paragangliomas had
      been reported but the synchronous non-functional paragangliomas of
      retroperitoneum and urinary bladder reported in this case is extremely rare and
      is not reported so far in English literature. 

PMID- 25859511
TI  - Giant omental fibromatosis presenting as pelvic mass.
AB  - Omental fibromatosis (abdominal desmoids) is a rare benign but locally aggressive
      neoplasm characterized by mass like or infiltrative growth of fibrous tissue. It
      usually arises from the abdominal wall or the extremities, however rarely it may
      also arise in the omentum, ileocolic mesentery, transverse or sigmoid mesocolon
      and ligamentum teres. Here, we present an 18-year-old male, who presented with
      lower abdominal pain and palpable lump in hypogastric region. Computed tomography
      of the abdomen showed large heterogeneous mass in lower abdomen, possibly arising
      from mesentery with regional adenopathy. Patient underwent exploratory laparotomy
      with a preoperative diagnosis of mesenteric tumour possibly gastrointestinal
      stromal tumour (GIST). Histopathological examination revealed the lesion as
      omental fibromatosis. To the best of our knowledge, very few cases of omental
      fibromatosis are noted in literature. Here, we describe a rare case of giant
      omental fibromatosis which resembled mesenteric GIST clinically but finally
      diagnosed as fibromatosis by histomorphology and immunohistochemistry (IHC). The
      present article describes fibromatosis of greater omentum and the difficulty in
      preoperative diagnosis, as it is frequently misdiagnosed as GIST. 

PMID- 25859513
TI  - Cutaneous angiosarcoma - a rare case report in Indian female!
AB  - Cutaneous angiosarcoma is a rare vascular tumour especially of elderly males. We
      present a rare case of elderly female who presented with scalp lesion, parotid
      swelling and posed a diagnostic challenge. Further work up including biopsy of
      the lesion revealed the diagnosis of cutaneous angiosarcoma. Rarity of the case
      due to presence of this rare tumour in a darkcolored female and wide spread
      presentation of the tumour prompted us to report the case. This case adds to the
      literature of few cases describing this rare tumour in Indian subcontinent. It
      attempts to alert the clinicians of this entity, as early diagnosis of the tumour
      may possibly improve the already known dismal prognosis! 

PMID- 25859514
TI  - Evaluation of adhesive bonding of lithium disilicate ceramic material with duel
      cured resin luting agents.
AB  - PURPOSE: The purpose of this vitro study was to comparatively evaluate the
      adhesive bonding of dual cured resin luting agents with lithium disilicate
      ceramic material. MATERIALS AND METHODS: Porcelain laminate veneers were prepared
      with lithium disilicate ceramic material i.e. IPS Empress II( E-Max Press). These
      laminates were bonded with RelyX ARC, Panavia F 2.0, Variolink II, Duolink and
      Nexus NX3.The porcelain laminates were etched with 9.6% hydrofluoric acid
      (Pulpdent Corporation) for one minute, washed for 15 sec with three way syringe
      and dried for 15 sec with air syringe. The silane (Ultradent) was applied with
      the help of applicator tip in a single coat and kept undisturbed for one minute.
      The prepared surfaces of the premolars were treated with 37% phosphoric acid
      (Prime dent) for 15 sec, thoroughly rinsed and dried as per manufactures
      instructions. The shear bond test was carried out on all samples with the
      Universal testing machine (Instron U.S.A.) The scanning electron microscopic
      study was performed at the fractured interface of representative samples from
      each group of luting agents. RESULT: In this study, the highest value of shear
      bond strength was obtained for NEXUS NX3 and the lowest for VARIOLINK II.
      CONCLUSION: The difference in bond strength can be interpreted as the difference
      in fracture resistance of luting agents, to which shearing load was applied
      during the shear bond strength test. It is inferred from this study that the
      composition of the luting agent determines the adhesive characteristics in
      addition to surface treatment and bonding surface area.

PMID- 25859515
TI  - Effect of Probiotic Containing Ice-cream on Salivary Mutans Streptococci (SMS)
      Levels in Children of 6-12 Years of Age: A Randomized Controlled Double Blind
      Study with Six-months Follow Up.
AB  - INTRODUCTION: To evaluate the caries risk based on the salivary levels of
      streptococcus mutans in children of 6-12 years of age group before and after
      consuming probiotic ice-cream containing Bifidobacterium lactis Bb-12 and
      Lactobacillus acidophilus La-5. MATERIALS AND METHODS: A double blind, placebo
      controlled trial was carried out in 60 children aged between 6 to 12 years with
      zero decayed, missing, and filled teeth (DMFT). They were randomly divided into
      two equal groups. Saliva sample were collected before the consumption of ice
      cream and Streptococcus mutans count was calculated and recorded as baseline
      data. For the next seven days both the groups were given ice creams marked as A
      and B. Saliva samples were collected after ice-cream consumption at the end of
      study period and also after a washout period of 30 days and again after six
      months. Samples were inoculated and colonies were counted. RESULTS: On
      statistical evaluation by students paired t-test, probiotic ice-cream brought
      significant reduction in the Streptococcus mutans count after seven days of ice
      cream ingestion (p<0.001) and also after 30 d of washout period (p<0.001). There
      was no significant reduction (p=0.076) by normal ice-cream consumption. After six
      months of the study period in both the groups the salivary levels of
      Streptococcus mutans was similar to the baseline. CONCLUSION: Probiotic ice-cream
      containing Bifidobacterium lactis Bb-12 and Lactobacillus acidophilus La-5 can
      cause reduction in caries causative organism. The dosage of the probiotic
      organisms for the long term or synergetic effect on the oral health are still
      needed to be explored.

PMID- 25859516
TI  - A Comparison of Platelet Count and Enrichment Percentages in the Platelet Rich
      Plasma (PRP) Obtained Following Preparation by Three Different Methods.
AB  - INTRODUCTION: Platelet rich plasma (PRP) represents an easily accessible and rich
      source of autologous growth factors. Different manual methods for the preparation
      of PRP have been suggested. Lacuna in knowledge exists about the efficacy of PRP
      preparation by these different manual methods. AIMS: This study was performed to
      determine the effects of centrifugation rate revolutions per minute (RPM) and
      time on the platelet count and enrichment percentages in the concentrates
      obtained following the three different manual methods of PRP preparation. SETTING
      AND DESIGN: In vitro experimental study. MATERIALS AND METHODS: This was an
      experimental study in which platelet concentration was assessed in the PRP
      prepared by three different protocols as suggested by Marx R (method 1), Okuda K
      (method 2) and Landesberg R (method 3). A total of 60 peripheral blood samples,
      (n=20 per method) were obtained from healthy volunteers. Baseline platelet count
      was assessed for all the subjects following which PRP was prepared. The platelet
      count in the PRP was determined using coulter counter (Sysmex XT 2000i).
      STATISTICAL METHOD: The mean of the platelet count obtained and their enrichment
      percentage were calculated and intergroup comparison was done (Tukey's HSD test).
      RESULTS: The number of platelets and enrichment percentage in PRP prepared by
      method 1 was higher compared to method 2 and method 3; this difference in
      platelet concentrates was found to be statistically significant (p < 0.05).
      CONCLUSION: The centrifugation rate and time appear to be important parameters,
      which influence the platelet yield. Method 1 which had lower centrifugation rate
      and time yielded a greater platelet count and enrichment percentage.

PMID- 25859517
TI  - Changes in Transforming Growth Factor-beta1 in Gingival Crevicular Fluid of
      Patients with Chronic Periodontitis Following Periodontal Flap Surgery.
AB  - INTRODUCTION: The aim of the study was to assess changes in Transforming Growth
      Factor- beta1 (TGF-beta1) levels in gingival crevicular fluid (GCF) and examine
      correlation of TGF-beta1 levels and periodontal parameters: probing pocket depth
      (PPD) and clinical attachment level (CAL) in sites with chronic periodontitis at
      various time intervals before and after periodontal surgery. MATERIALS AND
      METHODS: The effects of non-surgical and surgical therapy on periodontal
      parameters and GCF TGF-beta1 levels in 18 sites affected with chronic
      periodontitis were assessed upto 6 weeks post conventional flap surgery. GCF was
      collected and PPD, CAL recorded at Baseline. GCF was collected and PPD, CAL
      recorded at Pre-surgery and flap surgery performed. GCF was collected from all
      sites at Two Weeks Post-surgery. GCF was collected and PPD, CAL recorded at Six
      Weeks Post-surgery. The concentration of TGF-beta1 in GCF was determined using a
      human TGF-beta1 enzyme immunometric assay kit. RESULTS: Mean TGF-beta1
      concentrations were significantly reduced at Pre-surgery, at Two Weeks Post
      surgery and at Six Weeks Post-surgery (p<0.05) when compared to Baseline TGF
      beta1 values. There was a statistically significant reduction in PPD and gain in
      CAL following non-surgical and surgical therapy when compared to baseline
      (p<0.05). CONCLUSION: RESULTS indicate that TGF-beta1 may play a role in the
      pathogenesis and diagnosis of periodontal disease and could be considered as a
      disease predictive biomarker.

PMID- 25859518
TI  - Effect of intra-orifice barriers on the fracture resistance of endodontically
      treated teeth - an ex-vivo study.
AB  - INTRODUCTION: The purpose of this study was to evaluate and compare the fracture
      resistance of roots obturated with guttapercha using bonded amalgam, GC Light
      cure GIC (resin modified glass ionomer cement) and Tetric N Flow (flowable hybrid
      composite) as different intra orifice barriers. MATERIALS AND METHODS: Eighty
      freshly extracted mandibular premolars with straight roots were reduced to 14 mm
      from the coronal aspect. All canals were enlarged to size 30 and specimens were
      obturated with gutta percha cones, except for control group specimens the coronal
      3 mm of root fillings of all other group specimens were removed with the aid of
      heated plugger. All samples were randomly divided into 4 groups of 20 specimens
      each. They were control, Fuji GC LC GIC, Tetric N Flow and Bonded Amalgam. After
      the placement of the intra orifice barrier materials, specimens stored at 37(o)C
      and 100% humidity for one week to allow the materials to set completely. After
      one week, all the groups were subjected to fracture resistance testing by using
      Universal testing machine. RESULTS: Data was analysed for significance by ANOVA
      (Analysis of variance) and further pair wise comparison was performed by
      Benferroni test. Level of significance was taken as 0.05. Tetric N Flow group
      showed better fracture resistance as compared to all other groups and Control
      group is least among the groups. Fracture resistance of Tetric N Flow compared
      with bonded amalgam was statistically significant. CONCLUSION: Tetric N Flow and
      Fuji GC LC GIC can be used as intra-orifice barriers with good fracture
      resistance in endodontically treated teeth.

PMID- 25859519
TI  - Incidental findings on cone beam computed tomography and reasons for referral by
      dental practitioners in indore city (m.p).
AB  - INTRODUCTION: Cone beam computed tomography is a new diagnostic innovation to
      dental imaging. Despite the use of CBCT in oral and maxillofacial imaging,
      reports on its use either by individual practitioners or referral patterns to
      CBCT centers is lacking. Hence, a study was conducted to determine incidental
      findings on CBCT and reasons for referral by dental practitioners in Indore city.
      MATERIALS AND METHODS: A retrospective analysis of 795 records that were referred
      for CBCT imaging at Institutional and Oracal CBCT Centre, Indore was undertaken.
      Referrals from both within and outside institution, as well as from private
      practitioners were considered. The reason for CBCT referral, provision diagnosis,
      final diagnosis and any incidental diagnosis were recorded. RESULTS: This
      retrospective chart audit revealed that 56.7 % were male and 43.3% were females.
      Greatest source of patients was referred by oral surgeons (21.9%) followed by
      oral and maxillofacial radiologist (14.2%) and prosthodontist (9.3%). The most
      common reason for referral was for implant analysis (24.2%) and the most common
      incidental finding diagnosed by CBCT was oral malignancies. CONCLUSION: In
      Institutional set-up, CBCT referrals were mostly for the reason of planning
      implant placement followed by trauma whereas private practitioners used CBCT
      mostly for implant placement followed by impaction. CBCT was being utilized more
      by Oral surgeons in private sector whereas it in an Institutional setup majority
      of referrals from Department of Oral Diagnosis and Radiology. Findings that were
      most commonly diagnosed incidentally on CBCT were Orofacial malignancies followed
      maxillary sinus pathologies.

PMID- 25859520
TI  - Evaluation of Periodontal Risk in Adult Patients using Two Different Risk
      Assessment Models - A Pilot Study.
AB  - OBJECTIVE: The aim of the present study was to evaluate the periodontal risk of
      individuals using periodontal risk assessment (PRA) model and modified PRA model.
      MATERIALS AND METHODS: A total of 50 patients with chronic periodontitis, age 30
      60 years were selected randomly and charting of the periodontal status was
      performed and those who met the inclusion criteria were enrolled in the study.
      Parameters recorded were- percentage of sites with bleeding on probing (BOP),
      number of sites with pocket depths (PD) >= 5mm, number of the teeth lost, bone
      loss (BL)/age ratio, Clinical attachment loss(CAL)/age ratio, diabetic and
      smoking status, dental status, systemic factors like diabetes were assessed. All
      the risk factors were plotted on the radar chart in (PRA) and (mPRA) models,
      using Microsoft excel and periodontal risk were categorized as low, moderate and
      high risk. RESULTS: Among 50 patients 31 were in low risk, 9 in moderate risk,
      and 10 in high risk identified by modified (PRA) model, whereas 28 patients were
      in low risk, 13 in moderate risk and 9 in high risk identified by (PRA).
      Statistical analysis demonstrated that there was no significant difference
      between the risk scores (X(2) = 0.932 with degree of freedom = 2, P = 0.627).
      CONCLUSION: Both the periodontal risk models are effective in evaluating the risk
      factors and can be useful tool for predicting proper diagnosis, disease
      progression and therapeutic strategies during the supportive periodontal therapy.

PMID- 25859521
TI  - The comparative evaluation of the translucency of crowns fabricated with three
      different all-ceramic materials: an in vitro study.
AB  - INTRODUCTION: All-ceramic crowns with different core materials of different
      strength and aesthetics are available in recent years. The aesthetics of the
      crown depends mainly on the shade and translucency. Clinician should be aware of
      the quality and characteristics of these materials so that they will be able to
      opt for good material for successful clinical use. AIM AND OBJECTIVE: The aim of
      this study was to evaluate and compare the translucency of crowns fabricated with
      three different commercially available all-ceramic materials viz. Alumina - CAD
      CAM Procera, Lithium disilicate - Pressable IPS e.max Press, Zirconia - CAD-CAM
      Lava. MATERIALS AND METHODS: All-ceramic crowns (5 per each group and total of 15
      samples) were made of Alumina - CAD-CAM Procera (Group I), Lithium disilicate -
      Pressable IPS e.max Press (Group II), Zirconia - CAD-CAM Lava (Group III) and
      veneered with their respective layering ceramic. Evaluation for the Translucency
      (CR=Yb/Yw) over the White (Yw) and Black (Yb) backgrounds at the Incisal, Middle,
      Cervical, Mesial and Distal thirds of each crown were done using the
      Spectrophotometer. The results obtained were statistically analyzed by Paired t
      test (p<0.05) and Analysis of Variance (p<0.05) for the test of significance
      among the groups. RESULTS: Significant differences in the contrast ratios were
      obtained among the three Groups (p<0.001). In this study, Group II Lithium
      disilicate-Pressable IPS e.max Press showed higher translucency (0.54). Group III
      Zirconia - CAD-CAM Lava showed the least translucency (0.75) and the translucency
      of Group I Alumina - CAD-CAM Procera (0.7) was in between both the groups.
      CONCLUSION: Translucency of material gives fair idea to clinician for the choice
      of material in different zones during replacement and suitability for restoration
      in aesthetic zone. Selection of all ceramic system depends on the translucency
      needed for successful prosthesis of artificial tooth so that it mimics patient's
      natural dentition. The qualitative measurement of translucency will give the
      evidence for the clinicians during selection of high or low value translucent
      tooth for successful replacement. Lithium disilicate - Pressable IPS e.max Press
      is having better translucency in comparison with other two materials in our
      study.

PMID- 25859522
TI  - Comparison of diagnostic accuracy of conventional intraoral periapical and direct
      digital radiographs in detecting interdental bone loss.
AB  - BACKGROUND: Periodontitis is an inflammatory disease of the supporting tissues of
      the teeth caused by specific microorganisms, resulting in destruction of the
      periodontal ligament and alveolar bone. Progressive loss of alveolar bone is the
      salient feature of periodontal disease. Accurate detection of periodontal disease
      with the use of radiographs helps in diagnosis, treatment and prognosis. AIMS:
      The present study aims to compare the efficacy of conventional intraoral
      periapical (IOPA) and direct digital radiographs (RVG) in detecting interdental
      alveolar bone loss using intrasurgical (IS) measurements as the gold standard.
      MATERIALS AND METHODS: Thirty patients elected to undergo periodontal flap
      surgery with periodontitis computing to 60 interdental alveolar defects on
      mandibular first molars were considered. IOPA and RVG were captured using
      standardized techniques. Bone loss measurements in IOPA and RVG were compared to
      the IS measurements. STATISTICAL ANALYSIS: Statistical analysis was carried out
      using student t test and ANOVA with the help of SPSS software and p-value <0.05
      was considered as significant. RESULTS: Both IOPA and RVG underestimated the bone
      loss measurements when compared to IS measurements which was statistically
      significant (p<0.0001). Bone loss measurements in RVG were closer to IS
      measurements than IOPA. CONCLUSION: Both the radiographic techniques IOPA and RVG
      underestimated bone loss by 1.5-2.5 mm. RVG was superior to IOPA for the
      detection of interdental bone loss due to reduced time and radiation exposure to
      obtain the same diagnostic information.

PMID- 25859523
TI  - Relationship Between Occlusal Plane and Three Levels of Ala Tragus line in
      Dentulous and Partially Dentulous Patients in Different Age Groups: A Pilot
      Study.
AB  - STATEMENT OF PROBLEM: Correct orientation of the occlusal plane plays a vital
      role in achieving optimal aesthetics, occlusal balance and function of complete
      dentures. The use of ala tragus line for determination of occlusal plane has been
      a topic of debate over past many years. Also, the effect of age on level of ala
      tragal line has not been investigated in the past. PURPOSE: To determine the
      effect of age on location of Ala-Tragus line. MATERIALS AND METHODS: A total of
      180 patients (90 males and 90 females) were selected with complete dentition and
      were grouped according to their age in three age groups with 60 subjects in each
      age group (Group A: 20-35 y, Group B: 36-50 y, Group C: 51-65 y). Right lateral
      profile photographs were taken with subjects having fox plane placed intraorally
      parallel to occlusal plane. Reference points corresponding to inferior border,
      middle or superior border of tragus and inferior border of ala of nose were
      marked on photographs. These were joined to get three different levels of Ala
      Tragus line. Images were analysed photometrically and most parallel relationship
      was determined in between arms of fox plane (that represented the occlusal plane)
      and three different levels of ala tragus line. Data obtained was subjected to
      statistical analysis using Pearson chi-square and Likelihood-ratio chi-square
      test. RESULTS: Significant correlation was found between age and level of Ala
      Tragus line. The occlusal plane was found to be more parallel to Ala-tragus line
      when inferior border of tragus was considered as posterior reference point in
      young adult age group (20-35 y). In older age groups, occlusal plane was found to
      be more parallel to Ala-tragus line when middle of tragus was considered as
      posterior reference point. CONCLUSION: Within the limitations of this study, it
      can be concluded that a definite relationship exists in between age and level of
      ala tragus line.

PMID- 25859524
TI  - Microleakage evaluation around retrograde filling materials prepared using
      conventional and ultrasonic techniques.
AB  - INTRODUCTION: The importance of the retrograde cavity preparation and the
      material used to restore is of utmost importance to achieve successful surgical
      endodontics. AIM: The aim of the present study is to evaluate the apical micro
      leakage of root end cavities filled with Mineral trioxide aggregate, Biodentine
      and light cure GIC using two different cavity preparation techniques that is
      conventional bur preparation and ultrasonic tip preparation. MATERIALS AND
      METHODS: Eighty extracted single rooted human teeth (except mandibular incisors)
      with one canal, fully developed apices and without any major carious lesion are
      collected for the study. The teeth were sectioned at CEJ to standardize the
      length. Roots are instrumented upto master apical file 40 K size and obturated
      with gutta percha and AH plus sealer in lateral condensation technique. The teeth
      were then resected apically at 90 degrees  angle axis to the long axis of the
      root removing 3 mm of the apex. The teeth were divided in to four groups of 20
      each- * Group I- samples restored with MTA. * Group II- samples restored with
      Biodentine. * Group III- (Positive control group)- samples restored with Light
      activated GIC. * Group IV - (negative control group)- no filling material. Each
      group is divided into two subgroups (a, b) of ten teeth each 1. Retropreparation
      done with ultrasonic retrotip. 2. Retropreparation done with conventional bur.
      The teeth were then immersed in 0.5% Rhodamine B dye for 48 h. The teeth were
      split longitudinally and the interface between the restored material and the
      canal wall is observed under Confocal laser scanning microscope. Depth of dye
      penetration was examined under stereomicroscope. RESULTS: The statistical
      analysis was performed by One way ANOVA, t test. Pair wise comparision was done
      by Newman - Keuls multiple post hoc test. The mean values of Dye penetration for
      Group Ia (321.23), Group Ib (490.11), Group IIa (1065.14), Group IIb (1170.96),
      Group IIIa (1888.90), Group IIIb (2025.35). The samples prepared with ultrasonic
      retrotip showed less microleakage but it is statistically not significant.
      CONCLUSION: MTA showed significantly less microleakage when compared to
      Biodentine and light cure GIC and there is no statistical difference between the
      ultrasonic retrotip preparation and conventional bur preparation.

PMID- 25859525
TI  - Comparison of Time Required by D-RaCe, R-Endo and Mtwo Instruments for
      Retreatment: An in vitro Study.
AB  - INTRODUCTION: To evaluate and compare the amount of time required by three rotary
      NiTi instruments in removing gutta-percha from root canal during retreatment with
      hand file as control. MATERIALS AND METHODS: Eighty human mandibular premolars
      with single straight root canals were prepared and obturated by cold lateral
      condensation with gutta-percha and AH Plus sealer. After two weeks, the 80 teeth
      were divided into one control group and 3 retreatment groups (n = 20 each). Gutta
      percha was removed using H-files, the D-RaCe, or the Mtwo or the R-Endo
      retreatment systems. Retreatment time was calculated using stopwatch. RESULTS: D
      RaCe and Mtwo required significantly less time than R-Endo and hand file. Hand
      file took maximum time, which was significantly slower than all groups. However,
      D-RaCe and Mtwo retreatment time was statistically insignificant. CONCLUSION: D
      RaCe and Mtwo remove gutta-percha faster than R-Endo and Hand files.

PMID- 25859526
TI  - Comparative Evaluation of Antibacterial Efficacy of Six Indian Plant Extracts
      against Streptococcus Mutans.
AB  - INTRODUCTION: To assess the antimicrobial efficacy of six plant extracts of
      Indian origin often used as traditional medicine against standard strains of
      Streptococcus mutans. MATERIALS AND METHODS: The antimicrobial activity of six
      plant extracts was determined by the agar well diffusion method. The minimum
      inhibitory concentration (MIC) for the crude (raw), Organic solvent based,
      aqueous extracts was determined by the agar well diffusion method. RESULTS: Out
      of all the six extracts evaluated, organic solvent based and aqueous extracts of
      all the extracts were found to have variable antimicrobial activities against the
      oral pathogen. The crude extract of Garlic was the most effective against
      Streptococcus mutans with the highest zone of inhibition (24.62 mm) followed by
      the aqueous extract of Amla (19.47mm) and organic solvent based extract of Ginger
      (18.76 mm). CONCLUSION: Despite of the fact that the extracts were not pure
      compounds and antimicrobial results were obtained. This recommends the potency of
      these extracts. The figment of the derivation of antimicrobial compounds from
      plants seems lucrative as it will lead to the development of a phytomedicine to
      act against microbes.

PMID- 25859527
TI  - An in-vivo correlation analysis of the distance between lingual frenal attachment
      and mandibular incisal edge position as an aid in establishing mandibular
      occlusal plane in South Indian population.
AB  - STATEMENT OF PROBLEM: The aim of the study is to find the reliability in
      measuring the distance between the anterior attachment of the lingual frenum and
      the incisal edge of the mandibular central incisor on casts to be used as a pre
      extraction record. PURPOSE: The objective of this study is to give a range of
      numerical values from anterior attachment of lingual frenum to mandibular central
      incisors in a class I ridge relation in south Indian population, which may be
      used in establishing the vertical dimension of the edentulous patient and also to
      locate the mandibular incisors in teeth arrangement of complete denture
      fabrication. MATERIALS AND METHODS: One hundred subjects (50 males and 50
      females) under the age group of 21-28y, with class I dental relationship and who
      have never undergone orthodontic treatment were selected. Two models were made
      for each subject using irreversible hydrocolloid impression material and type III
      gypsum product to obtain an average value for each subject. The distance between
      the incisal edges of the lower central incisor and the anterior attachment of the
      lingual frenum is measured using a divider and digital vernier caliper.
      STATISTICAL ANALYSIS: Mean and Standard deviation using descriptive statistics
      tool using SPSS software version 18. RESULT: The distance between the anterior
      attachment of the lingual frenum and incisal edges of mandibular central incisors
      among the 100 subjects was 14.50mm +/- 2.2245 mm. CONCLUSION: The value obtained
      aided in establishing the vertical dimension easier by making a pre-determined
      height of mandibular occlusal rim.

PMID- 25859528
TI  - Knowledge and attitudes of general dental practitioners towards posterior
      composite restorations in northern saudi arabia.
AB  - INTRODUCTION: The restoration of posterior teeth with composite restoration is a
      common clinical practice nowadays. Opinions regarding posterior composite
      restorations vary among dentists. The aim of the present study was to determine
      the knowledge and opinions of general dental practitioners towards composite
      resins for posterior teeth restorations. MATERIALS AND METHODS: A questionnaire
      was devised to elicit information regarding placement of composite restoration in
      posterior teeth in northern Saudi Arabia. It was distributed to 230 dentists by
      hand and e-mail. A response rate 136 (59%) was obtained. The questionnaire sought
      details about case selection criteria for composite restoration, problems
      associated with composites and reasons for selecting composite restoration in
      posterior teeth. The data was processed and analysed by SPSS statistical software
      19. Frequencies and percentages were calculated for various responses of the
      participants. RESULTS: Regarding the selection of composite restoration in
      posterior teeth, 97% of the dentists did not prefer composite placement for class
      I restoration with heavy occlusal contacts. 83% of the participants did not
      select composite for class II restoration. 78% of the respondents opted for
      restoring composites in small defects. Patients' aesthetic demands (90%), amalgam
      replacement (22%) and restoration of endodontically treated teeth (42%) were the
      contributing factors. Regarding the problems associated with posterior composite
      restorations. Recurrent caries (87%), post-operative sensitivity (84%),
      restoration fracture (83%) and polymerization shrinkage (73%) were the major
      problems reported by respondents associated with composite restorations. The
      other minor concerns were wear (60%), contact build up in case of class II cavity
      restorations (51%) and isolation for composite restorations (36%). Conservative
      cavity preparation (78%), aesthetics (73%) and patient preference (65%) were the
      main reasons for choosing composite restoration for the posterior teeth.
      CONCLUSION: Posterior composites are not popular among dentists practicing in
      northern Saudi Arabia and there is a need of continued professional education and
      clinical training for the dentists for posterior composite restorations.

PMID- 25859529
TI  - Apicoectomy versus apexification.
AB  - The aim was to evaluate treatment outcomes after apicoectomy and apexification in
      adjacent non-vital maxillary central incisors with large periapical
      radiolucencies, in a 10-year-old boy. The patient had complained of tenderness in
      the upper central incisors on mastication and gave a history of trauma to those
      teeth three years ago. On examination, there were found to be non-vital.
      Apexification (using Metapex) and apicoectomy (obturation with gutta percha) were
      performed on 11 and 21, respectively. Radiographical observations were made six
      months, one year and two years, post-operatively. Apical repair was found to be
      more favorable after apicoectomy than apexification, for a non-vital maxillary
      central incisor with an open apex and large periapical radiolucency. 

PMID- 25859530
TI  - Recurrent mandibular supplemental premolars: a case report with 5 year follow up
      and review of literature.
AB  - A 12-year-old girl reported for a routine dental checkup. Radiographic survey
      disclosed the presence of two developing structures resembling premolars one on
      either side of the mandible in premolar region, which were of supplemental type
      and surgical removal of supernumerary premolars facilitated eruption of the left
      second premolar. On six months follow-up, there was radiographic evidence of
      another supernumerary premolar in the left side of mandible that is left in situ,
      patient is on regular follow-up. This emphasizes the importance of thorough
      clinical and radiographic examination, early diagnosis and follow-up of the
      developing dentition in children. The patient has been followed-up from the age
      of 12 year to 17 year. This paper describes a case of recurrent supplemental
      supernumerary premolars in the mandible along with review of literature. 

PMID- 25859531
TI  - Alveolar rhabdomyosarcoma on the left maxillary alveolus: a unique presentation.
AB  - Rhabdomyosarcomas (RMSs) are a group of soft-tissue malignant tumours. They
      derive from primitive skeletal muscle tissue with head and neck as its principle
      location. These tumours are extremely rare in adults and it is believed to have a
      different natural course, treatment response, and prognosis. The invasiveness of
      tumour, metastasis, lymph node involvement, and the age at diagnosis is a
      predictor of outcome in patients with RMC. Hence early recognition and
      histological sub-typing is of critical importance in the therapy of the disease.
      We report a rare case of RMC in a 50-year-old female patient involving the left
      maxillary alveolus with a detailed clinical, radiological, histopathological and
      immunohistochemical findings. 

PMID- 25859533
TI  - Dental management of cornelia de lange syndrome: a rare case report.
AB  - Cornelia de Lange syndrome (CdLS) is a rare, multiple congenital defect often
      called as Amsterdam dwarfism. The physical phenotype of CdLS includes low birth
      body weight, short stature and facio-cranial dysmorphia. The diagnosis of the
      syndrome is based on clinical grounds as there is no biochemical or chromosomal
      markers for CDLS that makes its diagnosis more complicated. The purpose of this
      paper is to present a clinical report of a boy emphasizing the importance of
      multidisciplinary approach for the diagnosis and treatment of this syndrome. 

PMID- 25859532
TI  - Unusual foreign body in a routine lateral cephalogram.
AB  - Routine radiographs made in the orthodontic office can often give way to
      detection and diagnosis of unusual syndromes, signs or foreign bodies. A case
      report of one such accidental detection of a very unusual foreign body within the
      nasal cavity of an orthodontic patient has been presented here to emphasize the
      importance of routine radiographic views, which over and above aiding in
      Orthodontic diagnosis, can also often detect potentially life threatening
      problems in the Oro-facial region. 

PMID- 25859534
TI  - Osteochondroma (OC) of the Condyle of Left Mandible: A Rare Case.
AB  - Osteochondroma (OC) is one of the most common benign condylar tumours having both
      chondroma and osteoma. However, this tumour is most frequently found on the
      metaphyses of long bones and is unusual on the skull. When it affects the
      mandibular condyle, the cause could be due to trauma to the tempero mandibular
      joint (TMJ). Here, in this report we present a rare case of osteochondroma of
      left condyle region in a 36-year-old man. The patient had noticed pain in the
      left TMJ for six months. The lesion is surgically removed and histologically
      evaluated which composed of chondrocytes dispersed in hyaline matrix along with a
      rim of calcified bone at one end. 

PMID- 25859535
TI  - Access to abutment screw in cement retained restorations: a clinical tip.
AB  - Abutment screw loosening has been reported to be the most common prosthetic
      complications occurring in screw retained as well as cement retained implant
      restorations. Different methods to treat this issue have been reported in the
      literature so far; however these have their own short-comings. Retrievability of
      an implant restoration intact becomes a clinical challenge when the restoration
      is cement retained especially with an angulated abutment. This technique is aimed
      at accurately determining the position of the abutment screw in 3 dimensional
      relationships using a vacuum formed clear stent. This technique can be used as a
      viable protocol for management of screw loosening in cement retained implant
      restorations. 

PMID- 25859536
TI  - Rushton bodies: an update.
AB  - Rushton bodies are peculiar, eosinophilic, linear, curved or straight,
      polycyclic, glassy structures occurring with variable frequency in the epithelial
      lining of odontogenic cysts, whose presence occasionally contributes to the
      diagnosis. Presence of these structures depends upon the sectioning plane of
      specimen. They are easily identifiable by their peculiar morphological and
      staining patterns. There is considerably ambiguity about the nature and
      epithelial, vascular, odontogenic or keratinous origin of these hyaline bodies.
      This article highlights the occurrence, light and electron microscopic features
      and histogenesis of Rushton bodies. 

PMID- 25859537
TI  - Human Epidermal Growth Factor Receptor 2 (HER2/neu) in Salivary Gland Carcinomas:
      A Review of Literature.
AB  - The aim of our study is to assess the relation of human epidermal growth factor
      receptor 2 or HER2/neu with the development of salivary gland carcinomas and use
      of Herceptin in the treatment of these cancers. A literature search was conducted
      using MEDLINE accessed via the National Library of Medicine PubMed interface
      searching for articles from 1994 up to 2014 relating to the existence of HER-2
      protein and gene in salivary gland carcinomas and HER2/neu targeted therapy,
      written in English language. Almost all the studies in literature reported a
      frequent over expression and amplification of HER2/nue in salivary duct
      carcinomas (SDC) compared to other salivary gland cancers. Herceptin given as a
      monotherapy was not effective. The data on Herceptin combined chemotherapy are
      potentially promising but inadequate to evaluate drug activity, as patients also
      received a variety of cytotoxic agents. Therefore, Herceptin contribution to
      tumour response outcomes could not be precisely determined and the total number
      of cases is not sufficient. It is recommended that further work involves a large
      series of HER2/neu positive salivary gland cancers (randomized control trial)
      treated with chemotherapy with and without Herceptin. This might need multi
      institutional cooperation. 

PMID- 25859538
TI  - Role of homeobox genes in tooth morphogenesis: a review.
AB  - In oral cavity, disturbances due to genetic alterations may range from lack of
      tooth development to morphological defects. Due to technical advances in genetic
      engineering and molecular biology, valuable information regarding dentofacial
      growth could be studied in detailed manner. This helped us to explain the
      aetiology and pathogenesis of many dentofacial disorders. The success in
      treatment lies first in determining the aetiology of tooth anomalies and finally
      differentiating the effect of genes and environment on the orofacial diseases of
      that particular individual. Several genes belonging to class II homeobox families
      are expressed during odontogenesis however homeobox genes are not directly
      imvolved in tooth formation as they are not directly expressed in the first
      branchial arch derivatives. 

PMID- 25859539
TI  - Effect of Platelet-Rich-Plasma (PRP) Implant Surface Topography on Implant
      Stability and Bone Revisited.

PMID- 25859540
TI  - Recent investigations of ergot alkaloids incorporated into plant and/or animal
      systems.

PMID- 25859541
TI  - Genome-wide identification of evolutionarily conserved alternative splicing
      events in flowering plants.
AB  - Alternative splicing (AS) plays important roles in many plant functions, but its
      conservation across the plant kingdom is not known. We describe a methodology to
      identify AS events and identify conserved AS events across large phylogenetic
      distances using RNA-Seq datasets. We applied this methodology to transcriptome
      data from nine angiosperms including Amborella, the single sister species to all
      other extant flowering plants. AS events within 40-70% of the expressed multi
      exonic genes per species were found, 27,120 of which are conserved among two or
      more of the taxa studied. While many events are species specific, many others are
      shared across long evolutionary distances suggesting they have functional
      significance. Conservation of AS event data provides an estimate of the number of
      ancestral AS events present at each node of the tree representing the nine
      species studied. Furthermore, the presence or absence of AS isoforms between
      species with different whole genome duplication (WGD) histories provides the
      opportunity to examine the impact of WDG on AS potential. Examining AS in gene
      families identifies those with high rates of AS, and conservation can distinguish
      ancient events vs. recent or species specific adaptations. The MADS-box and SR
      protein families are found to represent families with low and high occurrences of
      AS, respectively, yet their AS events were likely present in the MRCA of
      angiosperms. 

PMID- 25859542
TI  - A-to-I RNA Editing: Current Knowledge Sources and Computational Approaches with
      Special Emphasis on Non-Coding RNA Molecules.
AB  - RNA editing is a dynamic mechanism for gene regulation attained through the
      alteration of the sequence of primary RNA transcripts. A-to-I (adenosine-to
      inosine) RNA editing, which is catalyzed by members of the adenosine deaminase
      acting on RNA (ADAR) family of enzymes, is the most common post-transcriptional
      modification in humans. The ADARs bind double-stranded regions and deaminate
      adenosine (A) into inosine (I), which in turn is interpreted by the translation
      and splicing machineries as guanosine (G). In recent years, this modification has
      been discovered to occur not only in coding RNAs but also in non-coding RNAs
      (ncRNA), such as microRNAs, small interfering RNAs, transfer RNAs, and long non
      coding RNAs. This may have several consequences, such as the creation or
      disruption of microRNA/mRNA binding sites, and thus affect the biogenesis,
      stability, and target recognition properties of ncRNAs. The malfunction of the
      editing machinery is not surprisingly associated with various human diseases,
      such as neurodegenerative, cardiovascular, and carcinogenic diseases. Despite the
      enormous efforts made so far, the real biological function of this phenomenon, as
      well as the features of the ADAR substrate, in particular in non-coding RNAs, has
      still not been fully understood. In this work, we focus on the current knowledge
      of RNA editing on ncRNA molecules and provide a few examples of computational
      approaches to elucidate its biological function. 

PMID- 25859543
TI  - High mobility group a proteins as tumor markers.
AB  - Almost 30 years ago, overexpression of HMGA proteins was associated with
      malignant phenotype of rat thyroid cells transformed with murine retroviruses.
      Thereafter, several studies have analyzed HMGA expression in a wide range of
      human neoplasias. Here, we summarize all these results that, in the large
      majority of the cases, confirm the association of HMGA overexpression with high
      malignant phenotype as outlined by chemoresistance, spreading of metastases, and
      a global poor survival. Even though HMGA proteins' overexpression indicates a
      poor prognosis in almost all malignancies, their detection may be particularly
      useful in determining the prognosis of breast, lung, and colon carcinomas,
      suggesting for the treatment a more aggressive therapy. In particular, the
      expression of HMGA2 in lung carcinomas is frequently associated with the presence
      of metastases. Moreover, recent data revealed that often the cause for the high
      HMGA proteins levels detected in human malignancies is a deregulated expression
      of non-coding RNA. Therefore, the HMGA proteins represent tumor markers whose
      detection can be a valid tool for the diagnosis and prognosis of neoplastic
      diseases. 

PMID- 25859545
TI  - Check'-ing DLBCL.

PMID- 25859544
TI  - Towards patient-oriented diabetes care: results from two KORA surveys in southern
      Germany.
AB  - OBJECTIVE: This study aims to examine the relationship of diabetes care processes
      and patient outcomes with an expanded set of indicators regarding patient
      oriented care delivery, such as treatment satisfaction, the quality of patient
      physician relationship, and a wider range of patient outcomes such as self
      management, health behaviour, disease-related burden, and health-related quality
      of life (HRQL). METHODS: The study population consisted of 486 participants with
      type 2 diabetes in two population-based follow-up surveys, conducted in 2003 to
      2005 and 2006 to 2008 in Southern Germany. Data were self-reported and
      questionnaire-based, including the SF-12 for HRQL. Multiple regression models
      were used to identify associations between care processes and outcomes with
      adjustment for confounders. RESULTS: Frequent medical examinations increased the
      likelihood of self-monitoring activities, such as foot care. A positive patient
      experienced relationship with their physician is associated with higher adherence
      to medical recommendations, such as medication intake, and the score of the SF-12
      mental component. Participants with diabetes-related complications reported
      higher levels of medical examinations and multiprofessional care. CONCLUSIONS:
      Indicators of patient-oriented care should become an indispensable part of
      diabetes clinical practice guidelines with the aim of striving for more effective
      support of patients.

PMID- 25859546
TI  - Functional polymorphisms in cancer.

PMID- 25859547
TI  - TIC10/ONC201: a bend in the road to clinical development.

PMID- 25859548
TI  - BCC or not: Sufu keeps it in check.

PMID- 25859549
TI  - Fighting Neuroblastomas with NBAT1.

PMID- 25859550
TI  - Genomics of chromophobe renal cell carcinoma: implications from a rare tumor for
      pan-cancer studies.
AB  - Chromophobe Renal Cell Carcinoma (ChRCC) is a rare subtype of the renal cell
      carcinomas, a heterogenous group of cancers arising from the nephron. Recently,
      The Cancer Genome Atlas (TCGA) profiled this understudied disease using multiple
      data platforms, including whole exome sequencing, whole genome sequencing (WGS),
      and mitochondrial DNA (mtDNA) sequencing. The insights gained from this study
      would have implications for other types of kidney cancer as well as for cancer
      biology in general. Global molecular patterns in ChRCC provided clues as to this
      cancer's cell of origin, which is distinct from that of the other renal cell
      carcinomas, illustrating an approach that might be applied towards elucidating
      the cell of origin of other cancer types. MtDNA sequencing revealed loss-of
      function mutations in NADH dehydrogenase subunits, highlighting the role of
      deregulated metabolism in this and other cancers. Analysis of WGS data led to the
      discovery of recurrent genomic rearrangements involving TERT promoter region,
      which were associated with very high expression levels of TERT, pointing to a
      potential mechanism for TERT deregulation that might be found in other cancers.
      WGS data, generated by large scale efforts such as TCGA and the International
      Cancer Genomics Consortium (ICGC), could be more extensively mined across various
      cancer types, to uncover structural variants, mtDNA mutations, themes of tumor
      metabolic properties, as well as noncoding point mutations. TCGA's data on ChRCC
      should continue to serve as a resource for future pan-cancer as well as kidney
      cancer studies, and highlight the value of investigations into rare tumor types
      to globally inform principals of cancer biology. 

PMID- 25859551
TI  - Two preclinical tests to evaluate anticancer activity and to help validate drug
      candidates for clinical trials.
AB  - Current approaches to assessing preclinical anticancer activity do not reliably
      predict drug efficacy in cancer patients. Most of the compounds that show
      remarkable anticancer effects in preclinical models actually fail when tested in
      clinical trials. We blame these failures on the complexity of the disease and on
      the limitations of the preclinical tools we require for our research. This
      manuscript argues that this lack of clinical response may also be caused by poor
      in vitro and in vivo preclinical designs, in which cancer patients' needs are not
      fully considered. Then, it proposes two patient-oriented tests to assess in vitro
      and in vivo anticancer activity and to help validate drug candidates for clinical
      evaluation. 

PMID- 25859552
TI  - MEK5-ERK5 pathway associates with poor survival of breast cancer patients after
      systemic treatments.
AB  - The MEK5-ERK5 pathway is a mammalian mitogen-activated protein (MAP) kinase
      cascade that is not well studied compared to other MAP kinase cascades. Two
      independent studies by Al-Ejeh et al. and Ortiz-Ruiz et al. published in
      Oncotarget last year concluded that ERK5 is an attractive target in triple
      negative breast cancer. In this perspective, we briefly describe the findings of
      these studies and propose the use of pharmacological inhibition of ERK5 in
      combination with chemotherapy against triple negative breast cancer because MEK5
      ERK5 overexpression associates with poor survival of patients treated with
      chemotherapy. 

PMID- 25859553
TI  - SapC-DOPS nanovesicles: a novel targeted agent for the imaging and treatment of
      glioblastoma.
AB  - Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor.
      Classified by the World Health Organization (WHO) as grade IV astrocytoma, GBMs
      are extremely aggressive, almost always recur, and despite our best efforts,
      remain incurable. This review describes the traditional treatment approaches that
      led to moderate successes in GBM patients, discusses standard imaging modalities,
      and presents data supporting the use of SapC-DOPS, a novel proteoliposomal
      formulation with tumoricidal activity, as a promising diagnostic imaging tool and
      an innovative anti-cancer agent against GBM. 

PMID- 25859554
TI  - Genistein exerts anti-leukemic effects on genetically different acute myeloid
      leukemia cell lines by inhibiting protein synthesis and cell proliferation while
      inducing apoptosis - molecular insights from an iTRAQTM quantitative proteomics
      study.
AB  - Acute myeloid leukemia (AML) is a form of cancer that affects the hematopoietic
      precursor cells with lethal effects. We investigated the prospect of using
      genistein as an effective alternate therapy for AML. A two-cell line model, one
      possessing the FLT3 gene with the ITD mutation (MV4-11) and the other with the
      wildtype FLT3 gene (HL-60) has been employed. Our 8-plexed iTRAQTM-based
      quantitative proteomics analysis together with various functional studies
      demonstrated that genistein exerts anti-leukemic effects on both the AML cell
      lines. Genistein treatment on the AML cells showed that the drug arrested the
      mTOR pathway leading to down-regulation of protein synthesis. Additionally,
      genistein treatment is found to induce cell death via apoptosis. Contrasting
      regulatory effects of genistein on the cell cycle of the two cell lines were also
      identified, with the induction of G2/M phase arrest in HL-60 cells but not in MV4
      11 cells. Hence, our study highlights the potent anti-leukemic effect of
      genistein on AML cells irrespective of their genetic status. This suggests the
      potential use of genistein as an effective general drug therapy for AML patients.

PMID- 25859555
TI  - RAS mutations vary between lesions in synchronous primary colorectal cancer:
      testing only one lesion is not sufficient to guide anti-EGFR treatment decisions.
AB  - INTRODUCTION: Mutations in KRAS and NRAS genes are negative predictors of anti
      EGFR therapies response in metastatic colorectal cancer. There are few reports on
      RAS testing in synchronous primary colorectal cancer (SP-CRC) and a lack of
      recommendations on which tissue should be tested for the mutation in this
      disease. This study analyzed the RAS status of both lesions in SP-CRC patients
      and in their metastasis. MATERIALS AND METHODS: DNA was obtained from formalin
      fixed-paraffin-embedded tissue, and mutations were analyzed by pyrosequencing.
      RESULTS: RAS status was heterogeneous in 6 (75%) of 8 SP-CRC patients between
      primary lesions. Five showed heterogeneity regarding RAS mutational status, and
      from these, four presented with metastasis: 3 cases (75%) had WT metastatic
      tissue, and 1 case (25%) had mutated metastatic tissue. One patient showed
      divergence regarding RAS mutation type. DISCUSSION: RAS mutations vary
      significantly between SP-CRC lesions, and the status of the metastasis is
      unpredictable. Testing for RAS mutations in only 1 of the primary lesions can
      misguide clinical decisions and hind the predictive potential of anti-EGFR
      treatment. A more appropriate approach in metastatic SP-CRC is to test the
      metastatic tissue or both primary lesions for providing more accurate mutation
      scenery and support more assertive clinical decisions.

PMID- 25859556
TI  - Cannabinoids receptor type 2, CB2, expression correlates with human colon cancer
      progression and predicts patient survival.
AB  - Many studies have demonstrated that the endocannabinoid system (ECS) is altered
      in different tumor types, including colon cancer. However, little is known about
      the role of the ECS in tumor progression. Here we report the correlation between
      CB 2 expression and pathological data in a series of 175 colorectal cancer
      patients, as well as the response of the HT29 colon cancer-derived cell line upon
      CB 2 activation. CB 2 mRNA was detected in 28.6% of samples tested. It was more
      frequent in N+ patients and predicts disease free survival and overall survival
      in colon cancer. In positive samples, CB 2 was expressed with great intensity in
      tumor epithelial cells and correlated with tumor growth. Treatment of HT29 with
      CB 2 agonist revealed membrane loss of E-cadherin and SNAIL1 overexpression. A
      direct correlation between CB 2 and SNAIL1 expression was also found in human
      tumors. CB 2 receptor expression is a poor prognostic marker for colon cancer and
      the activation of this receptor, with non-apoptotic doses of agonists, could be
      collaborating with disease progression. These results raise the question whether
      the activation of CB 2 should be considered as anti-tumoral therapy. 

PMID- 25859557
TI  - TR4 nuclear receptor enhances prostate cancer initiation via altering the stem
      cell population and EMT signals in the PPARG-deleted prostate cells.
AB  - A recent report indicated that the TR4 nuclear receptor might suppress the
      prostate cancer (PCa) initiation via modulating the DNA damage/repair system.
      Knocking-out peroxisome proliferator-activated receptor gamma (PPARG), a nuclear
      receptor that shares similar ligands/activators with TR4, promoted PCa
      initiation. Here we found 9% of PCa patients have one allele of PPARG deletion.
      Results from in vitro cell lines and in vivo mouse model indicated that during
      PCa initiation TR4 roles might switch from suppressor to enhancer in prostate
      cells when PPARG was deleted or suppressed (by antagonist GW9662). Mechanism
      dissection found targeting TR4 in the absence of PPARG might alter the stem cell
      population and epithelial-mesenchymal transition (EMT) signals. Together, these
      results suggest that whether TR4 can enhance or suppress PCa initiation may
      depend on the availability of PPARG and future potential therapy via targeting
      PPARG to battle PPARG-related diseases may need to consider the potential side
      effects of TR4 switched roles during the PCa initiation. 

PMID- 25859559
TI  - Clinical next generation sequencing of pediatric-type malignancies in adult
      patients identifies novel somatic aberrations.
AB  - Pediatric malignancies in adults, in contrast to the same diseases in children
      are clinically more aggressive, resistant to chemotherapeutics, and carry a
      higher risk of relapse. Molecular profiling of tumor sample using next generation
      sequencing (NGS) has recently become clinically available. We report the results
      of targeted exome sequencing of six adult patients with pediatric-type
      malignancies : Wilms tumor(n=2), medulloblastoma(n=2), Ewing's sarcoma( n=1) and
      desmoplastic small round cell tumor (n=1) with a median age of 28.8 years.
      Detection of druggable somatic aberrations in tumors is feasible. However,
      identification of actionable target therapies in these rare adult patients with
      pediatric-type malignancies is challenging. Continuous efforts to establish a
      rare disease registry are warranted. 

PMID- 25859560
TI  - Versican is a potential therapeutic target in docetaxel-resistant prostate
      cancer.
AB  - In the current study, we investigated a combination of docetaxel and thalidomide
      (DT therapy) in castration-resistant prostate cancer (CRPC) patients. We
      identified marker genes that predict the effect of DT therapy. Using an androgen
      insensitive PC3 cell line, we established a docetaxel-resistant PC-3 cell line
      (DR-PC3). In DR-PC3 cells, DT therapy stronger inhibited proliferation/viability
      than docetaxel alone. Based on gene ontology analysis, we found versican as a
      selective gene. This result with the findings of cDNA microarray and validated by
      quantitative RT-PCR. In addition, the effect of DT therapy on cell viability was
      the same as the effect of docetaxel plus versican siRNA. In other words,
      silencing of versican can substitute for thalidomide. In the clinical setting,
      versican expression in prostate biopsy samples (before DT therapy) correlated
      with PSA reduction after DT therapy (p<0.05). Thus targeting versican is a
      potential therapeutic strategy in docetaxel-resistant prostate cancer. 

PMID- 25859561
TI  - Examining Emotion Regulation as an Outcome, Mechanism, or Target of Psychological
      Treatments.
AB  - This paper reviews the extant literature on emotion regulation (ER) in
      psychological interventions. First, we review current conceptualizations of ER,
      highlighting a model with established clinical utility (particularly with regard
      to the development of new interventions and modification of existing
      interventions). Next, we review the literature on the effects of psychological
      interventions on ER, from traditional cognitive-behavioral and acceptance-based
      behavioral interventions that do not target ER directly to treatments that
      directly target ER as one component of a larger or more comprehensive treatment,
      as well as the preliminary research examining ER as a mechanism of change in
      these treatments. Finally, extant data on three treatments developed specifically
      to address ER are reviewed, with an emphasis on the ER-specific treatment with
      the most empirical support to date (emotion regulation group therapy).

PMID- 25859558
TI  - Analysis and interpretation of transcriptomic data obtained from extended Warburg
      effect genes in patients with clear cell renal cell carcinoma.
AB  - BACKGROUND: Many cancers adopt a metabolism that is characterized by the well
      known Warburg effect (aerobic glycolysis). Recently, numerous attempts have been
      made to treat cancer by targeting one or more gene products involved in this
      pathway without notable success. This work outlines a transcriptomic approach to
      identify genes that are highly perturbed in clear cell renal cell carcinoma
      (CCRCC). METHODS: We developed a model of the extended Warburg effect and
      outlined the model using Cytoscape. Following this, gene expression fold changes
      (FCs) for tumor and adjacent normal tissue from patients with CCRCC (GSE6344)
      were mapped on to the network. Gene expression values with FCs of greater than
      two were considered as potential targets for treatment of CCRCC. RESULTS: The
      Cytoscape network includes glycolysis, gluconeogenesis, the pentose phosphate
      pathway (PPP), the TCA cycle, the serine/glycine pathway, and partial
      glutaminolysis and fatty acid synthesis pathways. Gene expression FCs for nine of
      the 10 CCRCC patients in the GSE6344 data set were consistent with a shift to
      aerobic glycolysis. Genes involved in glycolysis and the synthesis and transport
      of lactate were over-expressed, as was the gene that codes for the kinase that
      inhibits the conversion of pyruvate to acetyl-CoA. Interestingly, genes that code
      for unique proteins involved in gluconeogenesis were strongly under-expressed as
      was also the case for the serine/glycine pathway. These latter two results
      suggest that the role attributed to the M2 isoform of pyruvate kinase (PKM2),
      frequently the principal isoform of PK present in cancer: i.e. causing a buildup
      of glucose metabolites that are shunted into branch pathways for synthesis of key
      biomolecules, may not be operative in CCRCC. The fact that there was no increase
      in the expression FC of any gene in the PPP is consistent with this hypothesis.
      Literature protein data generally support the transcriptomic findings.
      CONCLUSIONS: A number of key genes have been identified that could serve as valid
      targets for anti-cancer pharmaceutical agents. Genes that are highly over
      expressed include ENO2, HK2, PFKP, SLC2A3, PDK1, and SLC16A1. Genes that are
      highly under-expressed include ALDOB, PKLR, PFKFB2, G6PC, PCK1, FBP1, PC, and
      SUCLG1.

PMID- 25859563
TI  - Dust Allergens within Rural Northern Rocky Mountain Residences.
AB  - To date, few studies have characterized allergens within residences located in
      rural areas of the northern Rocky Mountain region. In this study, we collected
      dust samples from 57 homes located throughout western Montana and northern Idaho.
      Dust samples were collected and later analyzed for dust mite allergens Der f 1
      and Der p 1, Group 2 mite allergens (Der p 2 and Der f 2), domestic feline (Fel d
      1), and canine (Can f 1). Indoor temperature and humidity levels were also
      measured during the sampling program, as were basic characteristics of each home.
      Dog (96%) and cat (82%) allergens were the most prevalent allergens found in
      these homes (even when a feline or canine did not reside in the home). Results
      also revealed the presence of dust mites. Seven percent (7%) of homes tested
      positive for Der p 1, 19% of homes were positive for Der f 1, and 5% of homes
      were positive for the Group 2 mite allergens. Indoor relative humidity averaged
      27.0 +/- 7.6% within the homes. Overall, humidity was not significantly
      associated with dust mite presence, nor was any of the other measured home
      characteristics. This study provides a descriptive assessment of indoor allergen
      presence (including dust mites) in rural areas of the northern Rocky Mountains,
      and provides new information to assist regional patients with reducing allergen
      exposure using in-home intervention strategies.

PMID- 25859564
TI  - Towards Scalable Graph Computation on Mobile Devices.
AB  - Mobile devices have become increasingly central to our everyday activities, due
      to their portability, multi-touch capabilities, and ever-improving computational
      power. Such attractive features have spurred research interest in leveraging
      mobile devices for computation. We explore a novel approach that aims to use a
      single mobile device to perform scalable graph computation on large graphs that
      do not fit in the device's limited main memory, opening up the possibility of
      performing on-device analysis of large datasets, without relying on the cloud.
      Based on the familiar memory mapping capability provided by today's mobile
      operating systems, our approach to scale up computation is powerful and
      intentionally kept simple to maximize its applicability across the iOS and
      Android platforms. Our experiments demonstrate that an iPad mini can perform fast
      computation on large real graphs with as many as 272 million edges (Google+
      social graph), at a speed that is only a few times slower than a 13" Macbook Pro.
      Through creating a real world iOS app with this technique, we demonstrate the
      strong potential application for scalable graph computation on a single mobile
      device using our approach.

PMID- 25859562
TI  - Role of endolysosomes and cholesterol in the pathogenesis of Alzheimer's disease:
      Insights into why statins might not provide clinical benefit.
AB  - Altered cholesterol homeostasis in general and increased levels of low-density
      lipoprotein (LDL) cholesterol specifically is a robust risk factor for the
      pathogenesis of sporadic Alzheimer's disease (AD). Because of this, the family of
      drugs known as statins have been tried extensively to lower cholesterol levels in
      attempting to prevent and/or lessen the neuropathogenesis of AD. Unfortunately,
      evidence accumulated to date is insufficient to support the continued use of
      statins as a viable pharmacotherapeutic approach against AD. To understand these
      complex and inter-related issues it is important to review how altered
      cholesterol homeostasis contributes to AD pathogenesis and why statins have not
      provided clinical benefit against AD. Apolipoproteins with their different
      affinities for various lipids and the receptors that control cholesterol uptake
      can result in drastic differences in cholesterol trafficking into and its
      distribution within neurons. The presence of the apoE4 or elevated plasma levels
      of LDL cholesterol can lead to a set of conditions that resembles lysosomal lipid
      storage disorders observed in Niemann-Pick type C disease such as impaired
      recycling of cholesterol back to the endoplasmic reticulum (ER), Golgi and plasma
      membranes, cholesterol deficiencies in plasma membranes, and increased
      cholesterol accumulation in endolysosomes resulting in endolysosome dysfunction.
      Consequently, the use of statins to block cholesterol synthesis in ER might not
      only decrease further plasma membrane cholesterol levels thus disturbing synaptic
      integrity, but also could also increase cholesterol burden in endolysosomes thus
      worsening endolysosome dysfunction. Therefore, it is not surprising that the use
      of cholesterol-lowering strategies with statins has not resulted in clinical
      benefit for patients living with AD.

PMID- 25859565
TI  - MAGE: Matching Approximate Patterns in Richly-Attributed Graphs.
AB  - Given a large graph with millions of nodes and edges, say a social network where
      both its nodes and edges have multiple attributes (e.g., job titles, tie
      strengths), how to quickly find subgraphs of interest (e.g., a ring of
      businessmen with strong ties)? We present MAGE, a scalable, multicore subgraph
      matching approach that supports expressive queries over large, richly-attributed
      graphs. Our major contributions include: (1) MAGE supports graphs with both node
      and edge attributes (most existing approaches handle either one, but not both);
      (2) it supports expressive queries, allowing multiple attributes on an edge,
      wildcards as attribute values (i.e., match any permissible values), and
      attributes with continuous values; and (3) it is scalable, supporting graphs with
      several hundred million edges. We demonstrate MAGE's effectiveness and
      scalability via extensive experiments on large real and synthetic graphs, such as
      a Google+ social network with 460 million edges.

PMID- 25859566
TI  - Inferring Meal Eating Activities in Real World Settings from Ambient Sounds: A
      Feasibility Study.
AB  - Dietary self-monitoring has been shown to be an effective method for weight-loss,
      but it remains an onerous task despite recent advances in food journaling
      systems. Semi-automated food journaling can reduce the effort of logging, but
      often requires that eating activities be detected automatically. In this work we
      describe results from a feasibility study conducted in-the-wild where eating
      activities were inferred from ambient sounds captured with a wrist-mounted
      device; twenty participants wore the device during one day for an average of 5
      hours while performing normal everyday activities. Our system was able to
      identify meal eating with an F-score of 79.8% in a person-dependent evaluation,
      and with 86.6% accuracy in a person-independent evaluation. Our approach is
      intended to be practical, leveraging off-the-shelf devices with audio sensing
      capabilities in contrast to systems for automated dietary assessment based on
      specialized sensors.

PMID- 25859567
TI  - Interactive Querying over Large Network Data: Scalability, Visualization, and
      Interaction Design.
AB  - Given the explosive growth of modern graph data, new methods are needed that
      allow for the querying of complex graph structures without the need of a
      complicated querying languages; in short, interactive graph querying is
      desirable. We describe our work towards achieving our overall research goal of
      designing and developing an interactive querying system for large network data.
      We focus on three critical aspects: scalable data mining algorithms, graph
      visualization, and interaction design. We have already completed an approximate
      subgraph matching system called MAGE in our previous work that fulfills the
      algorithmic foundation allowing us to query a graph with hundreds of millions of
      edges. Our preliminary work on visual graph querying, Graphite, was the first
      step in the process to making an interactive graph querying system. We are in the
      process of designing the graph visualization and robust interaction needed to
      make truly interactive graph querying a reality.

PMID- 25859568
TI  - Influence of insertion techniques for resin cement and mechanical cycling on the
      bond strength between fiber posts and root dentin.
AB  - PURPOSE: To evaluate the effect of the insertion technique for resin cement and
      mechanical cycling on the bond strength between fiber posts and root dentin.
      MATERIALS AND METHODS: Sixty-four single-rooted bovine teeth were endodontically
      prepared to receive glass-fiber posts. The insertion of cement into the root
      canal was performed using one of the following techniques: POS, insertion with
      the post; LEN, the use of a lentulo-type drill; EXP, insertion with a straight
      tip explorer; or CEN, the use of a Centrix syringe. Half of the specimens were
      mechanically cycled. All specimens were sectioned into slices of 1.8 mm for the
      push-out test and 0.5 mm for analysis of the cement layer quality. RESULTS: The
      insertion technique affected the interaction between factors (bond strength and
      mechanical cycling; p < 0.0001). Insertion of the Centrix syringe after
      mechanical cycling showed the highest bond values (13.6 +/- 3.2 MPa). Group-to
      group comparisons for baseline and cycled conditions indicated that mechanical
      cycling significantly influenced the bond strength (p < 0.0001) of the POS and
      CEN groups. The quality of the cement layer did not differ between the techniques
      when evaluated in the middle (p = 0.0612) and cervical (p = 0.1119) regions, but
      did differ in the apical region (p = 0.0097), where the CEN group had better
      layer quality for the two conditions tested (baseline and cycled). CONCLUSION:
      The use of the Centrix syringe improved the homogeneity of the cement layer,
      reducing the defects in the layer and increasing adhesive strength values to
      dentin, even after mechanical cycling.

PMID- 25859569
TI  - Effect of Conditioning and Aging on the Bond Strength and Interfacial Morphology
      of Glass-ionomer Cement Bonded to Dentin.
AB  - PURPOSE: To determine the bond stability and the change in interfacial
      ultrastructure of a conventional glassionomer cement bonded to dentin, with and
      without pretreatment using a polyalkenoic acid conditioner. MATERIALS AND
      METHODS: The occlusal dentin surfaces of 10 teeth were ground flat. Glass-ionomer
      cement was bonded to the surfaces either with or without polyalkenoic acid
      conditioning. The teeth were sectioned into 1-mm2 stick-shaped specimens. The 200
      specimens obtained were randomly assigned to four groups with different periods
      of storage in water: 1 week, 1 month, 3 months, and 6 months. The microtensile
      bond strength (MUTBS) was determined for each storage time. Additional specimens
      were prepared for transmission electron microscopy (TEM); they were produced with
      or without prior polyalkenoic acid conditioning in the same manner as for the
      MUTBS test. RESULTS: There was no significant difference in MUTBS to conditioned
      dentin (p > 0.05). After 6 months of aging, the MUTBS to non-conditioned dentin
      was significantly reduced as compared to the 1-week, 1-month, and 3-month results
      (p < 0.05). The failures appeared to be of a mixed nature, although aging caused
      more areas of cohesive than adhesive failure in all groups. TEM observation
      showed a demineralized layer and an amorphous gel phase in the polyalkenoic acid
      conditioned group. CONCLUSION: Aging did not reduce the bond strength of the
      conventional glass-ionomer cement to dentin when the surface was pretreated with
      a polyalkenoic acid conditioner.

PMID- 25859575
TI  - Label-free fluorescence detection of mercury ions based on the regulation of the
      Ag autocatalytic reaction.
AB  - In this work, a novel facile nanoparticle autocatalytic sensor based on the
      inhibition of the Ag autocatalytic reaction for the determination of Hg(2+) was
      developed. o-Phenylenediamine (OPD) tended to be oxidized into 2,3
      diaminophenazine (OPDox) by silver ions (Ag(+)) followed by the formation of
      silver nanoparticles (AgNPs). Employed as a catalyst, the thus-formed AgNPs would
      further promote the reaction between OPD and Ag(+). When Hg(2+) was introduced,
      Hg(2+) adsorbed on the surface of the AgNPs, thus inhibiting the oxidation
      process mentioned above and achieving weakened fluorescence intensity. A linear
      relationship between fluorescence intensity and Hg(2+) concentration (within the
      range from 10 nM to 2500 nM) was obtained and the detection limit reached as low
      as 8.2 nM. The proposed method was also applied for the determination of Hg(2+)
      in real water samples with satisfactory results. The protocol showed excellent
      advantages of sensitivity and selectivity for Hg(2+) over various metal ions and
      anions. Meanwhile, this method was simpler and more cost-effective compared with
      many reported nanomaterial- and DNA-based approaches. Furthermore, an "INHIBIT"
      logic gate based on the Ag(+)-Hg(2+)-OPD system has also been designed. 

PMID- 25859576
TI  - Personal, social and environmental risk factors of problematic gambling among
      high school adolescents in Addis Ababa, Ethiopia.
AB  - Understanding risk factors of problematic gambling is prerequisite to effective
      intervention design to alleviate the negative consequences of gambling. This
      study explored the personal, social and environmental risk factors of problematic
      gambling in four high schools in Addis Ababa, Ethiopia, among students (N = 422)
      ranging from 12 to 21 years of age. Results from the cross-sectional survey
      showed that personal feelings (e.g., self-esteem, false perceptions about
      winning, drug abuse), social factors (e.g., peer influence, parental gambling),
      and environmental factors (e.g., accessibility of gambling venues,
      advertisements) were significant correlates of problematic gambling. The study
      also revealed that men were more at risk for severe problematic gambling than
      females. Among the identified types of gambling activities, the most prevalent
      ones were playing cards followed by flipping coin and pool gambling while
      internet gambling was among the least reported gambling activities. By
      identifying personal, social and environmental correlates of risky gambling
      activities this study provides evidence-based information for the systematic
      design and evaluation of educational interventions to prevent problematic
      gambling in young people.

PMID- 25859577
TI  - Validation of the Gambling Refusal Self-Efficacy Questionnaire for Chinese
      undergraduate students.
AB  - Although research on self-efficacy in the gambling literature took place more
      than 25 years ago, only in the recent decade did researchers attempt to develop
      valid and reliable measures of gambling-related self-efficacy. Recently Casey et
      al. (J Gambl Stud 24:229-246, 2008) developed the Gambling Refusal Self-Efficacy
      Questionnaire (GRSEQ) in an Australian sample, which is a valuable tool for
      gambling research. The first objective of this study is to validate the measure
      in a new sample. Given that previous research on Chinese's gamblers' self
      efficacy is lacking, and that related research often used ad-hoc measures of the
      construct, a second objective of this study is to evaluate whether the GRSEQ is
      suitable for Chinese people. A sample of 427 university students (56.4 % females,
      50.7 % gamblers) answered a questionnaire with measures including the GRSEQ,
      subjective norms, intentions toward gambling, general self-efficacy,
      impulsiveness, and pathological gambling symptoms. Evidence was found for the
      four-factor structure, internal consistency, criterion-related validity, and
      discriminant validity of the Chinese version of the GRSEQ among this young
      Chinese group.

PMID- 25859578
TI  - On finding the C in CBT: the challenges of applying gambling-related cognitive
      approaches to video-gaming.
AB  - Many similarities have been drawn between the activities of gambling and video
      gaming. Both are repetitive activities with intermittent reinforcement, decision
      making opportunities, and elements of risk-taking. As a result, it might be
      tempting to believe that cognitive strategies that are used to treat problem
      gambling might also be applied to problematic video gaming. In this paper, we
      argue that many cognitive approaches to gambling that typically involve a focus
      on erroneous beliefs about probabilities and randomness are not readily
      applicable to video gaming. Instead, we encourage a focus on other clusters of
      cognitions that relate to: (a) the salience and over-valuing of gaming rewards,
      experiences, and identities, (b) maladaptive and inflexible rules about
      behaviour, (c) the use of video-gaming to maintain self-esteem, and (d) video
      gaming for social status and recognition. This theoretical discussion is advanced
      as a starting point for the development of more refined cognitive treatment
      approaches for problematic video gaming.

PMID- 25859579
TI  - A medical mystery.

PMID- 25859580
TI  - Hands on stamps: hands from Michelangelo's Creation of Adam.

PMID- 25859581
TI  - Hand of Buddha.

PMID- 25859582
TI  - Hands on stamps: Praying hands.

PMID- 25859583
TI  - Retraction. Cyclobacterium qasimii sp. nov., a psychrotolerant bacterium isolated
      from a marine sediment of Kongsfjorden, Svalbard.
AB  - The authors would like to retract this publication in order to improve the
      chemotaxonomic data as it has become apparent that there are inconsistencies in
      the data presented in this paper. This paper has been retracted from IJSEM Papers
      in Press and will not be published in print in IJSEM.

PMID- 25859584
TI  - Retraction. Cecembia lonarensis gen. nov., sp. nov., a novel haloalkalitolerant
      bacterium of the family Cyclobacteriaceae, isolated from a haloalkaline lake and
      emended descriptions of the genera Indibacter, Nitritalea, Belliella and
      Aquiflexum.
AB  - The authors would like to retract this publication in order to improve the
      chemotaxonomic data as it has become apparent that there are inconsistencies in
      the data presented in this paper. This paper has been retracted from IJSEM Papers
      in Press and will not be published in print in IJSEM.

PMID- 25859586
TI  - Evidence and policy: mind the gap.

PMID- 25859585
TI  - [Hard times... redoubled determination!].

PMID- 25859587
TI  - [Team work].

PMID- 25859588
TI  - [The next Congress of the SPCCTV].

PMID- 25859589
TI  - Species-specific Standardisation of Licorice by Metabolomic Profiling of
      Flavanones and Chalcones.
AB  - INTRODUCTION: Major phenolics from licorice roots (Glycyrrhiza sp.) are
      glycosides of the flavanone liquiritigenin (F) and its 2'-hydroxychalcone isomer,
      isoliquiritigenin (C). As the F and C contents fluctuate between batches of
      licorice, both quality control and standardisation of its preparations become
      complex tasks. OBJECTIVE: To characterise the F and C metabolome in extracts from
      Glycyrrhiza glabra L. and Glycyrrhiza uralensis Fisch. ex DC. by addressing their
      composition in major F-C pairs and defining the total F:C proportion. MATERIAL
      AND METHODS: Three types of extracts from DNA-authenticated samples were analysed
      by a validated UHPLC/UV method to quantify major F and C glycosides. Each extract
      was characterised by the identity of major F-C pairs and the proportion of Fs
      among all quantified Fs:Cs. RESULTS: The F and C compositions and proportions
      were found to be constant for all extracts from a Glycyrrhiza species. All G.
      uralensis extracts contained up to 2.5 more Fs than G. glabra extracts. Major F-C
      pairs were B-ring glycosidated in G. uralensis, and A-/B-ring apiosyl
      glucosidated in the G. glabra extracts. The F:C proportion was found to be linked
      to the glycosidation site: the more B-ring F-C glycosides were present, the
      higher was the final F:C proportion in the extract. These results enable the
      chemical differentiation of extracts from G. uralensis and G. glabra, which are
      characterised by total F:C proportions of 8.37:1.63 and 7.18:2.82, respectively.
      CONCLUSION: Extracts from G. glabra and G. uralensis can be differentiated by
      their respective F and C compositions and proportions, which are both useful for
      further standardisation of licorice botanicals.

PMID- 25859590
TI  - Data science: Industry allure.

PMID- 25859591
TI  - Response.

PMID- 25859592
TI  - Commentary:Would your  health be better if you lived  in England or in the USA?

PMID- 25859593
TI  - Response.

PMID- 25859594
TI  - Commentary:  Environmental chemicals and  diabetes: which ones are we missing?

PMID- 25859595
TI  - Response.

PMID- 25859597
TI  - Response.

PMID- 25859596
TI  - CD41 T cell recovery during suppression of HIV  replication: an international
      comparison of the  immunological efficacy of antiretroviral therapy  in North
      America, Asia and Africa.
AB  - BACKGROUND: Even among HIV-infected patients who fully suppress plasma HIV RNA
      replication on antiretroviral therapy, genetic (e.g. CCL3L1 copy number), viral
      (e.g. tropism) and environmental (e.g. chronic exposure to microbial antigens)
      factors influence CD4 recovery. These factors differ markedly around the world
      and therefore the expected CD4 recovery during HIV RNA suppression may differ
      globally. METHODS: We evaluated HIV-infected adults from North America, West
      Africa, East Africa, Southern Africa and Asia starting non-nucleoside reverse
      transcriptase inhibitorbased regimens containing efavirenz or nevirapine, who
      achieved at least one HIV RNA level <500/ml in the first year of therapy and
      observed CD4 changes during HIV RNA suppression. We used a piecewise linear
      regression to estimate the influence of region of residence on CD4 recovery,
      adjusting for socio-demographic and clinical characteristics. We observed 28 217
      patients from 105 cohorts over 37 825 person-years. RESULTS: After adjustment,
      patients from East Africa showed diminished CD4 recovery as compared with other
      regions. Three years after antiretroviral therapy initiation, the mean CD4 count
      for a prototypical patient with a pre-therapy CD4 count of 150/ml was 529/ml [95%
      confidence interval (CI): 517-541] in North America, 494/ml (95% CI: 429-559) in
      West Africa, 515/ml (95% CI: 508-522) in Southern Africa, 503/ml (95% CI: 478
      528) in Asia and 437/ml (95% CI: 425-449) in East Africa. CONCLUSIONS: CD4
      recovery during HIV RNA suppression is diminished in East Africa as compared with
      other regions of the world, and observed differences are large enough to
      potentially influence clinical outcomes. Epidemiological analyses on a global
      scale can identify macroscopic effects unobservable at the clinical, national or
      individual regional level.

PMID- 25859598
TI  - Creativity in medicine.

PMID- 25859599
TI  - [Glial fibrillary acidic protein: the component of intermediate filaments in the
      vertebrate brain astrocytes].
AB  - Glial fibrillary acidic protein (GFAP) refers to the type III intermediate
      filament proteins and is the essential component of the cytoskeleton in
      astrocytes of all vertebrates. This review presents current data on the molecular
      organization of GFAP in a comparative aspect. The results of most relevant
      studies using immunocytochemical labeling of the protein are summarized. The data
      on the changes in expression of GFAP in Alexander disease caused by the primary
      pathology of astrocytes are presented.

PMID- 25859600
TI  - [Novel achievements in development and application of GPCR-peptides].
AB  - One of the approaches to creating the regulators of G-protein-coupled receptors
      (GPCR) is the development of peptides that structurally correspond to the
      functionally important regions of the intracellular extracellular loops of the
      receptors. GPCR-peptides can selectively regulate the functional activity of
      homologous receptor and affect the hormonal signal transduction via the receptor.
      Among the peptides corresponding to the intracellular regions of GPCR, their
      derivatives modified with hydrophobic radicals exhibit the highest activity and
      selectivity of action in vitro and in vivo. Ample evidence demonstrates that
      lipophilic GPCR-peptides may be used to treat diseases and various abnormalities
      that depend on the functional activity of receptors homologous to them. In turn,
      the peptides corresponding to the extracellular regions of GPCR can be used as
      functional probes for studying the specific interaction between the receptors and
      their ligands, as well as for studying the etiology and pathogenesis of
      autoimmune diseases caused by the production of antibodies to GPCR antigenic
      determinants that are localized in the receptor extracellular loops. The present
      review focuses on the recent achievements in development and application of GPCR
      peptides and on the prospects for their further use in medicine and fundamental
      biology.

PMID- 25859601
TI  - [Characterization of the intestinal digestive glycosidases in plankton- and
      benthos-feeding species of the fish genus Ballerus (Cyprinidae)].
AB  - The activity of hydrolases (maltase, saccharase, amylolytic activity) in the
      intestinal mucosa of the plankton-feeding zope Ballerus ballerus and the benthos
      feeding white-eye bream Ballerus sapa was investigated. The temperature
      characteristics of maltase hydrolysis (T(opt) and E(act)) are similar in both
      species. The lower K(m) of maltase hydrolysis in the white-eye bream reflects a
      higher enzyme/substrate affinity and indicates a more effective carbohydrate
      hydrolysis in the benthos-versus plankton-feeding species. The glycosidase
      activity in the white-eye bream is twice as high as in the zope. This may be due
      not only to different feeding spectra and biochemical food contents but also to
      the differences in thyroid status of species under consideration.

PMID- 25859602
TI  - [The activity of transaminases in the tissues of the Black-Sea mollusk Mytilus
      galloprovincialis].
AB  - The activities of aspartate aminotransferase (AST, E. C. 2.6.1.1) and alanine
      aminotransferase (ALT, E. C. 2.6.1.2) were studied in the tissues of the bivalve
      mollusks differing in shell color. Shell color patterns were assessed by
      photographing and computer processing in Adobe Photoshop CS-3. The activity of
      transaminases was determined by the Reitman-Frankel procedure. Four color groups
      of mollusks were singled out: black, intermediate, dark- and light brown. The AST
      and ALT activities were found to increase as shells lose color probably
      reflecting different tolerance of mollusks to habitats with different
      concentration of oxygen. The ALT distribution pattern differs appreciably in the
      foot of M. galloprovincialis where the highest values were found in the black
      colored mussels, evidently due to the change of the predominant enzyme function.
      In this tissue, the reaction of transamination replenishes the pool of free amino
      acids required for the synthesis of byssus threads.

PMID- 25859603
TI  - [Thresholds of continuously approaching sound sources with rhythmic structures
      typical for biologically significant signals].
AB  - Localization of biologically significant moving rhythmic sources with different
      pulse/pause ratio has been practically not investigated. The issue of the
      perception thresholds of continuously approaching sound sources is addressed in
      the present study. The illusion of approaching sound courses was created by noise
      pulse sequences linearly increasing in amplitude and emitted by a loudspeaker
      placed at the level of the subject's head, 1.1 m away, under free field
      conditions. The sequences were formed by short (5 and 10 ms) or long (70 and 100
      ms) pulses. The continuous movement thresholds were evaluated by the pauses
      between noise pulses varying from 10 to 150 ms. For the short pulse sequences the
      thresholds were 49 and 41 ms, while for the long ones they decreased to 21 and 16
      ms, respectively. A progressive decay of the continuous movement perception
      threshold in pausing between noise pulses with increasing width over the whole
      pulse-width range studied was observed. The thresholds for the short noise pulse
      sequences were 54 and 51 ms did not differ significantly, while for the long
      noise pulse sequences they were almost twice as long, 91 and 115 ms. For the
      structures representing the short (up to 10 ms) pulse sequences, the thresholds
      were highly variable in magnitude that is indicative of a probabilistic
      evaluation of movement in case of insufficient information. For the long (tens of
      ms) pulse sequences, the threshold evaluation was stabilized. The continuous
      movement thresholds and the effective masking time for sound pulse sequences
      coincided suggesting critical role of non-simultaneous masking for the evaluation
      of movement continuity.

PMID- 25859604
TI  - [Species-specific features of tocopherol content in carnivorous mammals during
      autumn period].
AB  - A comparative study of the major liposoluble antioxidant, vitamin E (alpha
      tocopherol), content was conducted in carnivorous mammals (polar fox, silver fox,
      raccoon dog, mink, sable) during late autumn under natural lowering of
      temperature. The highest vitamin E content in liver and kidney was found in polar
      fox and raccoon dog, obviously due to seasonal metabolic changes and ecological
      specialization determining the accumulation of considerable amounts of tocopherol
      both in polar and hibernating species. To investigate the features of vitamin E
      accumulation, the tocopherol loading experiment was implemented on three species
      (polar fox, silver fox, mink). It was shown that polar fox, as compared to
      silverfox and mink, exhibits a higher ability to reserve vitamin E. The
      established differences in tocopherol content and distribution in different
      species should be considered as a genetically fixed reaction to the effect of
      environment underlain by metabolic differences in animals with different
      ecological specialization. The ability of tocopherol to accumulate in tissues and
      organs allows considering its essential role in stabilization of the antioxidant
      system and ensuring thereby a seasonal cold resistance.

PMID- 25859605
TI  - [Osphradial chemosensory organ as a probable trigger of the cardiac system
      adaptive reaction to the effect of heavy metals in aquatic mollusks].
AB  - The responses of osphradium in the fresh-water mollusk Viviparus sp. and single
      osphradial neurons in the pond snail Lymnaea stagnalis to L-glutamine and L
      asparagine as well as the changes in these responses under the effect of heavy
      metals (Cu, Cd) were recorded electrophysiologically. The functional connections
      of osphradium with the identified neurons of the central pattern generator of
      respiratory movements and cardiac activity as well as the modification of these
      connections under the effect of short-term application of HgCl2 solution on the
      snail's osphradium were investigated. The cardiac rhythm in the mollusk Littorina
      littorea under the effect of Cu ions was registered non-invasively in long
      lasting experiments. The dose-dependent short-term effects of heavy metals
      changes after osphradium injury were revealed. The implication of osphradium in
      adaptive reactions of the cardiac system in aquatic mollusks to the environmental
      heavy metal pollution is suggested. The dependence of cardiac rhythm on the
      degree of accumulation of copper ions in the mollusk tissues was detected. The
      results obtained are essential for unraveling neural mechanisms and pathways
      allowing heavy metals to affect the functional state of hydrobionts,
      particularly, the cardiac activity frequency characteristics of which are widely
      used as informative biomarkers to assess physiological condition of aquatic
      invertebrates.

PMID- 25859606
TI  - [Erythrocytes of hetero- and homoiothermal animals in natural and artificial
      hypothermia].
AB  - By the low-angle light scattering technique there are revealed peculiarities of
      dynamics of transformation (osmotic fragility, level of hemolysis and ratio of
      forms by index of sphericity) of erythrocytes of hetero- (golden hamsters
      Mesocricetus auratus) and homoiothermal (white rats Rattus norbegicus) animals in
      natural hibernation and suspended animation, craniocerebral and immersion
      hypothermia. In control in hamsters the osmotic fragility and the level of
      hemolysis of erythrocytes were higher than in rats, predominant were modified
      forms (in particular stomatocytes). Under artificial hypothermia, regardless of
      the way of achievement, depth and duration, we observed changes similar in
      direction, but different in expression: the osmotic fragility and hemolysis
      increased, the portion of discocytes decreased (especially sharply in hamsters
      under suspended animation), the number of changed erythrocytic forms rose. In
      contrast, under hiberation the osmotic fragility, hemolysis and the amount of
      stomatocytes declined, the portion of discocytes increased, but at the same time
      the amount of prehemolytic forms (spherocytes) rose too. In 24 hs there occurred
      a decrease of osmotic fragility (after suspended animation more pronounced in
      hamsters) and the level of hemolysis (especially after immersion hypothermia),
      the portion of discocytes was restored, in hamsters after suspended animation and
      in rats after immersion hypothermia it even exceeded the control level;
      spherocytes in blood of hamsters were not revealed, in rats they were elevated.
      Possibly, the observed qualitative change of population of spherocytes 24 h after
      hypothermia toward its homogeneity is determined not only at the level of
      elimination of old and defected cells, activation of erythropoiesis, the
      appearance of highly resistant erythrocytes, but also at the level of time
      membrane-stabilizing mechanisms.

PMID- 25859607
TI  - [Functional topography of pacemaker and conducting myocytes in the right
      atrioventricular valve of the chicken (Gallus domesticus) heart].

PMID- 25859608
TI  - [Comparative properties of pyruvate kinase and lactate dehydrogenase from muscles
      of pigeons with motor activity and hypodynamia].

PMID- 25859609
TI  - [<RNA World"--an unlikely scenario of the life origin and early ecolution on
      Earth].
AB  - The most widely accepted modern scenario of prebiotic evolution that led to the
      emergence of the first cells on our planet is the "RNA World"--a hypothetical
      period of the early Earth's biosphere, when the information transfer and all the
      processes necessary for the functioning of the primary systems were provided by
      replicating RNA molecules. The essence of the "RNA World" hypothesis is based on
      two postulates: 1) at the initial stages of the origin of life, RNA molecules
      performed all functions necessary for reproduction and replication of biological
      molecules: informational, catalytic and structural; 2) at a certain stage of
      evolution arose separation of RNA and DNA, appeared genetically encoded proteins
      and occurred a transition to the modern world of living systems functioning.
      However, the analysis shows that the hypothesis of "RNA World" has a number of
      unsurmountable problems of chemical and informational nature. The biggest of them
      are: a) the unreliability of the initial components synthesis; b) a catastrophic
      rise of polynucleotide chains instability with their elongation; c)
      catastrophically low probability of formation of sequences possessing meaningful
      information; d) lack of a mechanism determining the regularities division of the
      membrane vesicles permeable to nitrogen bases and other RNA components; e) lack
      of driving forces for the transition from the RNA world to the much more complex
      world based on DNA and RNA. Therefore, the "RNA World" scenario seems unlikely.

PMID- 25859610
TI  - Adolescent tramadol use and abuse in Egypt.
AB  - BACKGROUND: Tramadol abuse liability is underestimated and the evidence of abuse
      and dependence is emerging. It has many health and social consequences especially
      in adolescents. Tramadol abuse has not been well studied in Egypt. The aim of
      this study was to estimate the prevalence and associated correlates of tramadol
      use and abuse among school students in Egypt. METHODS: A total of 204 students,
      aged 13-18 years, from six schools in Zagazig, Egypt, were screened for tramadol
      use using The Drug Use Disorders Identification Test and a urine screen for
      tramadol. RESULTS: The prevalence of tramadol use was 8.8% among school students
      and the average age at onset of tramadol use was 16.5 +/- 1.1. Some 83% of the
      users were using tramadol alone while the rest (17%) were using a combination of
      tramadol, alcohol, and cannabis. Two-thirds of these students started with
      tramadol as the first drug after the onset of tobacco smoking. Over one third of
      tramadol users had drug-related problems and 6% had dependence. There was a
      significant association between tramadol use and older age, male gender, and
      smoking. Drug-related problems were negatively correlated with age at onset of
      tramadol use. CONCLUSIONS: Tramadol use was common among adolescents and over one
      third of tramadol users had drug-related problems. Population-based longitudinal
      studies are needed to investigate tramadol use and the possible role of tramadol
      as a gateway drug in the development of substance abuse in Egypt.

PMID- 25859612
TI  - A molecular structure matching approach to efficient identification of endogenous
      mammalian biochemical structures.
AB  - Metabolomics is the study of small molecules, called metabolites, of a cell,
      tissue or organism. It is of particular interest as endogenous metabolites
      represent the phenotype resulting from gene expression. A major challenge in
      metabolomics research is the structural identification of unknown biochemical
      compounds in complex biofluids. In this paper we present an efficient
      cheminformatics tool, BioSMXpress that uses known endogenous mammalian
      biochemicals and graph matching methods to identify endogenous mammalian
      biochemical structures in chemical structure space. The results of a
      comprehensive set of empirical experiments suggest that BioSMXpress identifies
      endogenous mammalian biochemical structures with high accuracy. BioSMXpress is 8
      times faster than our previous work BioSM without compromising the accuracy of
      the predictions made. BioSMXpress is freely available at
      http://engr.uconn.edu/~rajasek/BioSMXpress.zip. 

PMID- 25859611
TI  - Real-Time Monitoring of ATP-Responsive Drug Release Using Mesoporous-Silica
      Coated Multicolor Upconversion Nanoparticles.
AB  - Stimuli-responsive drug delivery vehicles have garnered immense interest in
      recent years due to unparalleled progress made in material science and
      nanomedicine. However, the development of stimuli-responsive devices with
      integrated real-time monitoring capabilities is still in its nascent stage
      because of the limitations of imaging modalities. In this paper, we describe the
      development of a polypeptide-wrapped mesoporous-silica-coated multicolor
      upconversion nanoparticle (UCNP@MSN) as an adenosine triphosphate (ATP)
      responsive drug delivery system (DDS) for long-term tracking and real-time
      monitoring of drug release. Our UCNP@MSN with multiple emission peaks in UV-NIR
      wavelength range was functionalized with zinc-dipicolylamine analogue (TDPA
      Zn(2+)) on its exterior surface and loaded with small-molecule drugs like
      chemotherapeutics in interior mesopores. The drugs remained entrapped within the
      UCNP-MSNs when the nanoparticles were wrapped with a compact branched
      polypeptide, poly(Asp-Lys)-b-Asp, because of multivalent interactions between Asp
      moieties present in the polypeptide and the TDPA-Zn(2+) complex present on the
      surface of UCNP-MSNs. This led to luminescence resonance energy transfer (LRET)
      from the UCNPs to the entrapped drugs, which typically have absorption in UV
      visible range, ultimately resulting in quenching of UCNP emission in UV-visible
      range while retaining their strong NIR emission. Addition of ATP led to a
      competitive displacement of the surface bound polypeptide by ATP due to its
      higher affinity to TDPA-Zn(2+), which led to the release of the entrapped drugs
      and subsequent elimination of LRET. Monitoring of such ATP-triggered ratiometric
      changes in LRET allowed us to monitor the release of the entrapped drugs in real
      time. Given these results, we envision that our proposed UCNP@MSN-polypeptide
      hybrid nanoparticle has great potential for stimuli-responsive drug delivery as
      well as for monitoring biochemical changes taking place in live cancer and stem
      cells. 

PMID- 25859613
TI  - Reliability and Intersession Agreement of Microperimetric and Fixation
      Measurements Obtained with a New Microperimeter in Normal Eyes.
AB  - PURPOSE: To evaluate the reliability and intersession agreement of measurements
      of retinal sensitivity as well as of the fixation pattern obtained in healthy
      eyes with a microperimeter integrating the mechanism of the scanning laser
      ophthalmoscope (SLO) with the static perimetry. METHODS: This study included a
      sample of 44 healthy eyes of 44 subjects of a mean age of 27.0 +/- 8.5 years. In
      all cases, microperimetric exams with the MAIA system (Centervue, Padova, Italy)
      were performed in three different sessions to evaluate the intersession
      repeatability. The consistency of measurements was analyzed by using the Friedman
      test and by analyzing the correlation between consecutive measurements. Agreement
      between the first and third sessions was assessed by using the Passing-Bablok
      regression analysis. The following parameters were analyzed: average threshold
      (AT), macular integrity (MI) index, fixation indexes P1 and P2, bivariate contour
      ellipse area (BCEA), major and minor axes of the ellipse and high preferred
      retinal locus position (PRLh). RESULTS: Not statistically significant differences
      were found in the evaluated parameters between the three sessions (p >= 0.193).
      The correlation between consecutive measurements was moderate to strong for all
      parameters evaluated (r >= 0.49, p < 0.01), except for the MI and the position of
      the PRLh (r <= 0.305, p >= 0.05). The Passing-Bablok regression analysis showed a
      good agreement between the first and third measurement for all parameters, except
      for the MI and the position of the PRLh. CONCLUSION: MAIA MP system is able to
      provide consistent measurements of AT and fixation in normal subjects. MI and the
      position of PRLh seem to be the least reliable parameters in this group of
      patients.

PMID- 25859614
TI  - Newly fabricated magnetic lanthanide oxides core-shell nanoparticles in
      phosphoproteomics.
AB  - Metal oxides show high selectivity and sensitivity toward mass spectrometry based
      enrichment strategies. Phosphopeptides/phosphoproteins enrichment from biological
      samples is cumbersome because of their low abundance. Phosphopeptides are of
      interest in enzymes and phosphorylation pathways which lead to the clinical links
      of a disease. Magnetic core-shell lanthanide oxide nanoparticles (Fe3O4@SiO2
      La2O3 and Fe3O4@SiO2-Sm2O3) are fabricated, characterized by SEM, FTIR, and EDX
      and employed in the enrichment of phosphopeptides. The nanoparticles enrich
      phosphopeptides from casein variants, nonfat milk, egg yolk, human serum and HeLa
      cell extract. The materials and enrichment protocols are designed in a way that
      there are almost no nonspecific bindings. The selectivity is achieved up to
      1:8500 using beta-casein/BSA mixture and sensitivity down to 1 atto-mole. Batch
      to-batch reproducibility is high with the reuse of core-shell nanoparticles up to
      four cycles. The enrichment followed by MALDI-MS analyses is carried out for the
      identification of phosphopeptides from serum digest and HeLa cell extract.
      Characteristic phosphopeptides of phosphoproteins are identified from human serum
      after the enrichment, which have the diagnostic potential toward prostate cancer.
      Thus, the lanthanide based magnetic core-shell materials offer a highly selective
      and sensitive workflow in phosphoproteomics. 

PMID- 25859615
TI  - PGF2alpha levels in Day 8 blood plasma are increased by the presence of one or
      more embryos in the uterus.
AB  - In cattle, the detection of very early endometrial responses is considered to be
      hampered by the presence of only a single embryo. Therefore, we have previously
      developed a model of multiple embryo transfer to circumvent this hindrance. In
      this work, we analysed embryo-maternal interactions in the bovine uterus on day 8
      of development while comparing the presence of multiple v. single embryos using
      embryo transfer and artificial insemination, respectively. Concentration of
      proteins (beta-actin, NFkB, clusterin and immunoproteosome 20S beta5i subunit
      i20S), by western blot, and hexoses (glucose and fructose) were measured in
      paired samples of uterine fluid (UF) from the same animal with and without
      embryos in the uterus and were compared with UF obtained after artificial
      insemination. Prostaglandin (PG) F2 alpha and PGE2 concentrations were also
      analysed in blood plasma. The four proteins analysed and hexoses were unaffected
      by the presence of one or more embryos in the uterus. However, blood PGF2 alpha
      showed similar, significant increases with one or more embryos over cyclic
      animals; such changes were not observed in blood PGE2. Although multiple embryo
      transfer may appear to be non-physiological, we showed that the uterus, at the
      very early embryonic stages, does exhibit physiological reactions. Multiple
      embryo transfer can, therefore, be used for studies of very early embryo-maternal
      interactions in vivo in monotocous species. 

PMID- 25859616
TI  - Exploring the role of cognitive and structural forms of social capital in
      HIV/AIDS trends in the Kagera region of Tanzania - a grounded theory study.
AB  - The article presents a synthesis of data from three village case studies focusing
      on how structural and cognitive social capital may have influenced the
      progression of the HIV epidemic in the Kagera region of Tanzania. Grounded theory
      was used to develop a theoretical model describing the possible links between
      structural and cognitive social capital and the impact on sexual health
      behaviours. Focus group discussions and key informant interviews were carried out
      to represent the range of experiences of existing social capital. Both structural
      and cognitive social capital were active avenues for community members to come
      together, empower each other, and develop norms, values, trust and reciprocal
      relations. This empowerment created an enabling environment in which members
      could adopt protective behaviours against HIV infection. On the one hand, we
      observed that involvement in formal and informal organisations resulted in a
      reduction of numbers of sexual partners, led people to demand abstinence from
      sexual relations until marriage, caused fewer opportunities for casual sex, and
      gave individuals the agency to demand the use of condoms. On the other hand,
      strict membership rules and regulations excluded some members, particularly
      excessive alcohol drinkers and debtors, from becoming members of the social
      groups, which increased their vulnerability in terms of exposure to HIV. Social
      gatherings (especially those organised during the night) were also found to
      increase youths' risk of HIV infection through instances of unsafe sex. We
      conclude that even though social capital may at times have negative effects on
      individuals' HIV-prevention efforts, this study provides initial evidence that
      social capital is largely protective through empowering vulnerable groups such as
      women and the poor to protect against HIV infection and by promoting protective
      sexual behaviours. 

PMID- 25859617
TI  - Delays in presenting for tuberculosis treatment associated with fear of learning
      one is HIV-positive.
AB  - A cornerstone of tuberculosis (TB) control is early diagnosis and treatment. The
      first hurdle that prospective TB patients must overcome is to present at a public
      health clinic for treatment. The Global Plan to Stop TB addresses the new
      challenges of the intersecting epidemics of TB and HIV, and it aims to cut the
      transmission chain by achieving early and effective treatment of all people with
      TB infection. This goal may be more difficult to achieve in practice. Findings
      from a representative community survey conducted in an area of high HIV
      prevalence in the Eastern Cape Province of South Africa suggest that patients
      must conquer fear of knowing their HIV status in order to present for TB
      diagnosis and treatment. A total of 1 020 adults residing in a low-income suburb
      of Grahamstown, Makana Municipality, participated in a questionnaire survey that
      probed attitudes and opinions about TB and HIV/AIDS-related issues. The
      respondents were presented with eight factors previously cited in the literature
      as causing delays in presenting for TB treatment at a public health clinic. The
      single largest proportion of respondents attributed delay to a fear of
      discovering that one is HIV-positive. While the vast majority of the respondents
      agreed that knowing one's HIV status is a civic responsibility ('the right thing
      to do'), half indicated that the lack of privacy during voluntary counselling and
      testing for HIV at a public health clinic acts as a disincentive. The evidence
      suggests that a fear of knowing one's HIV status is a deep-seated anxiety that is
      often not openly acknowledged, and that it is intertwined with the stigma related
      to the 'new' TB associated with HIV and AIDS. It is crucial to allay this deep
      seated fear in the general public so that South Africa's integrated HIV and TB
      services, designed to accelerate control of the twin epidemics, are successful. 

PMID- 25859618
TI  - A qualitative exploration of the impact of HIV and ART on social disruption and
      household continuity in Uganda.
AB  - With increased uptake of antiretroviral therapy (ART) throughout sub-Saharan
      Africa, it is critical to have a better understanding of the impact of ART on all
      health dimensions since the treatment can have the expected benefits as well as
      unintended negative consequences. We conducted semi-structured interviews with 24
      adult HIV clients (19 women and 5 men) in Uganda who had been on ART for at least
      six months. A grounded approach and content analysis were used to explore the
      effects of having HIV and undergoing ART on household continuity, social
      engagement, experience of support and stigma, and children's school attendance.
      Most of the participants reported loss of a spouse/partner and household
      discontinuity (e.g. having to move in with extended family) because of HIV, and
      this was largely unchanged after being on ART. While experiences of HIV stigma
      and social disengagement were common after an HIV diagnosis, most participants
      reported improved social interaction after having commenced ART, which for some
      was tied to economic productivity. Many of the participants' children who had
      stopped going to school were able to return after the parent was on ART. HIV care
      and ART, with related improvements in clients' physical and work-related
      functioning, together with family support, helped to reverse some of the
      deleterious effects of having HIV. Nonetheless, support that augments healthcare
      is needed to help individuals provide for themselves and their families, both
      socially and economically. 

PMID- 25859619
TI  - Masculinity and sexual practices in the military: a South African study.
AB  - The military's organisational culture tends to condone or encourage risk-taking
      behaviour. Willingness to accept and engage in risk-taking behaviour is central
      to good soldiering and is strongly associated with readiness for combat. This
      core attribute of military culture might predispose soldiers to engage in other
      higher-risk behaviours, such as unprotected sex. Soldiers' working and living
      conditions, such as the high level of work-related stress in combat and
      deployment situations, and being away from home and particularly from partners
      for long periods, are reported as contributing to high levels of HIV in military
      groups. This article explores the underlying value system in the military context
      as a strong enabler of higher-risk sexual practices among male soldiers. This not
      only obstructs gender equality in the military organisation but also impacts on
      the prevalence of HIV. The article derives from a qualitative study of a diverse
      sample of 23-33-year-old male South African soldiers. Semi-structured interviews
      were conducted with 14 fulltime soldiers and the interview transcripts were
      analysed through interpretive discourse analysis. The findings highlight that
      when soldiers are on deployment or attending military courses they are often
      tempted to engage in higher-risk sexual behaviours. Underlying this narrative are
      patriarchal notions that men 'need' sex and cannot endure being without it, and
      that they have the right therefore to demand it from their partner or to seek it
      from multiple partners. Male soldiers' sexual practices appear to be rationalised
      predominantly on the basis of the 'male sexual drive' discourse. The research
      found an association between work in the military and higher-risk sexual
      activity. Therefore, we argue that tackling HIV in the military demands critical
      examination of the constructions of masculinity. 

PMID- 25859620
TI  - Why do some South African ethnic groups have very high HIV rates and others not?
AB  - The differences in HIV prevalence between South Africa's racial/ethnic groups
      (19.9%, 3.2%, and 0.5% among 15-49-year-old blacks, coloureds and whites,
      respectively) are as big as those between the countries with the highest and
      lowest levels of HIV prevalence worldwide. These large racial/ethnic differences
      are largely determined by different sexual network structures. In networks among
      black South Africans, sexual partnerships are more likely to be arranged
      concurrently - a configuration that leads to exponential increases in the spread
      of HIV. An examination of the historical origins of polygamy (where it is
      normative for partnerships to be arranged concurrently) and monogamy (serial or
      lifetime) reveals that it is the practice of universal monogamy in stratified
      societies which is the outlier. The ideology and practice of universal monogamy
      originated in Europe as the result of several factors, most prominently conflicts
      between the Christian Church and the nobility. After its imposition in Europe,
      the European colonial project would see this ideology disseminated around the
      world. Under the influence of liberalism it would mutate into a secular and
      unacknowledged value-programme of monogamy as a universal norm. This value
      programme and practice of monogamy (mostly serial) is still the norm for white
      South Africans; thus, this sexual behaviour 'spandrel' (by-product of other
      historical processes) is a large contributor to the lower levels of HIV
      prevalence among whites. In pre-colonial African societies, polygyny was
      normative, and the Christian value-programme of monogamy never achieved the
      hegemonic status it did in Europe and other areas of conquest. Married black
      African men who converted to Christianity were no less likely to have additional
      sexual partners, but only more likely to conceal them. The ongoing secrecy about
      having concurrent partners has contributed to the connectedness of sexual
      networks among black Africans at large and in this manner has contributed to the
      rapid spread of HIV. 

PMID- 25859621
TI  - Formative evaluation of the STAR intervention: improving teachers' ability to
      provide psychosocial support for vulnerable individuals in the school community.
AB  - The article describes the pilot phase of a participatory reflection and action
      (PRA) study. The longitudinal investigation explores teachers' ability to provide
      psychosocial support within the context of HIV/AIDS following an asset-based
      intervention. The study ensued from our desire to understand and contribute to
      knowledge about the changed roles of teachers due to adversity in the community,
      specifically in relation to HIV/AIDS and education. The supportive teachers,
      assets and resilience (STAR) intervention was facilitated from November 2003 to
      October 2005 and consisted of the research team undertaking nine field visits and
      facilitating 20 intervention sessions (2-3 hours each), and 12 post-intervention
      research visits have been conducted to date. Ten female teachers were selected
      for participation through random purposeful sampling at a primary school in an
      informal settlement outside Port Elizabeth, South Africa. Data-generation
      included PRA activities, observation, informal interactive interviews, and focus
      group discussions. The data were analysed by means of inductive thematic
      analysis. We found that the teachers did not view vulnerability as being related
      to children or HIV/AIDS in isolation, but rather that their psychosocial support
      to children and the school community was inclusive across a spectrum of
      vulnerabilities and services. We argue that teachers who are inclined to provide
      such support will fulfil this role irrespective of understanding policy or
      receiving training. We contend that teachers are well-positioned to manage school
      based psychosocial support in order to create relevant and caring spaces for
      vulnerable individuals in the school community. 

PMID- 25859622
TI  - Use of a simulation game for HIV/AIDS education with pre-service teachers.
AB  - The article describes the use of a simulation game in HIV/AIDS education with pre
      service teachers in Johannesburg, South Africa. The use of a simulation game, as
      novel experiential pedagogy, was an attempt to raise awareness about HIV and AIDS
      and to demonstrate that anyone can be at risk of HIV infection. Using a generic
      qualitative research design, the data were collected over a three-year period by
      way of video recordings of the simulation game, recordings of large and small
      group discussions afterwards, and via questionnaires and written reflections by
      the education students four weeks afterwards. Content analysis and discourse
      analysis led to the construction of three main themes. First, we found that the
      novelty factor of the simulation game for raising HIV/AIDS awareness was
      confirmed both during the game itself and after a period of time had elapsed.
      Second, in light of many education students' naivety about the intersection of
      biological, socio-cultural and economic issues at play in the spread of HIV, the
      game prompted more reflexivity about the disease and helped to broaden the
      participants' discussions. Lastly, the data revealed the disjuncture between
      theory and practice in HIV/AIDS education. We propose that in raising awareness
      of HIV and AIDS, educators should move towards more engaging and challenging
      pedagogies that address the learning needs of the 'new' generation of university
      students. 

PMID- 25859623
TI  - Pre- and post-intervention assessment of a PMTCT-programme-strengthening
      initiative in a rural area of the Eastern Cape, South Africa.
AB  - The research assesses prevention-of-mother-to-child-transmission-of-HIV (PMTCT)
      services following implementation of programme-strengthening activities in a
      municipality in the Eastern Cape Province, South Africa. A pre-intervention and
      post-intervention design was used to conduct facility assessments and client exit
      interviews at baseline and after 28 months. For the facility assessments,
      unstructured interviews were conducted with the heads of maternity wards at each
      delivery facility (n = 4), nurses (n = 9) and lay counsellors (n = 18). District
      Health Information System (DHIS) records were used to assess changes on PMTCT
      programme indicators. Observations were conducted at the fixed clinics and
      hospitals to determine compliance to the national criteria for PMTCT-services
      delivery. For the exit interviews with clients, the pre- and post-assessment
      samples, respectively, included women attending for antenatal care (n = 296; n =
      239) as well as HIV-positive women attending for postnatal care (n = 70; n =
      142). The personnel generally perceived the PMTCT services as having been
      strengthened as a result of the initiative and the DHIS records showed positive
      changes. Client exit interviews revealed significant increases in the numbers of
      women who: were aware of the PMTCT programme; were tested for HIV during their
      pregnancy; were aware of VCT before coming to the facility; knew their HIV-test
      result; and, had helpful pre-HIV-test and/or post-HIV-test counselling
      experiences. The long waiting periods at the facilities and the relatively short
      length of the counselling sessions remained a serious concern. Lessons learnt may
      help with designing strategies to expand the national programme in South Africa
      as well as PMTCT programmes elsewhere. 

PMID- 25859624
TI  - Sexuality among the elderly in Dzivaresekwa district of Harare: the challenge of
      information, education and communication campaigns in support of an HIV/AIDS
      response.
AB  - This ethnographic study in Dzivaresekwa district, Harare, Zimbabwe, examines the
      issue of sexuality among the elderly and their challenges in accessing
      information, education, and communication (IEC) campaigns in the face of HIV and
      AIDS. The research depended heavily on collecting life histories through key
      informant interviews. The theory of structuration (as proposed by Anthony
      Giddens) was adopted as a framework to analyse the findings. The findings reveal
      that although the sample of elderly people in Dzivaresekwa district were sexually
      active, HIV/ AIDS-related interventions in the form of IEC campaigns mainly focus
      on the age group of 14-49-year-olds, and otherwise consider the elderly only as a
      group indirectly affected by the epidemic and less at risk of HIV infection. This
      is mainly a result of society's presumption that people withdraw from sexual life
      with advanced age. Thus, the elderly are incorrectly regarded as sexually
      inactive and not susceptible to contracting sexually transmitted infections. A
      fuller understanding of the sexuality of the elderly is important to increase the
      usefulness HIV/AIDS efforts, while IEC campaigns that target them are still
      needed. 

PMID- 25859625
TI  - Twelve-year mortality in HIV-infected patients receiving antiretroviral therapy:
      the role of social vulnerability. The ANRS CO8 APROCO-COPILOTE cohort.
AB  - BACKGROUND: Although the role of clinical/biological factors associated with
      mortality has already been explored in HIV-infected patients on antiretroviral
      therapy (ART), to date little attention has been given to the potential role of
      social vulnerability. This study aimed to construct an appropriate measure of
      social vulnerability and to evaluate whether this measure is predictive of
      increased mortality risk in ART-treated patients followed up in the ANRS CO8
      APROCO-COPILOTE cohort. METHODS: The cohort enrolled 1,281 patients initiating a
      protease inhibitor-based regimen in 1997-1999. Clinical/laboratory data were
      collected every 4 months. Self-administered questionnaires collected psycho
      social/behavioural characteristics at enrolment (month [M] 0), M4 and every 8-12
      months thereafter. A multiple correspondence analysis using education, employment
      and housing indicators helped construct a composite indicator measuring social
      vulnerability. The outcome studied was all-cause deaths occurring after M4. The
      relationship between social vulnerability and mortality, after adjustment for
      other predictors, was studied using a shared-frailty Cox model, taking into
      account informative study dropout. RESULTS: Over a median (IQR) follow-up of 7.9
      (3.0-11.2) years, 121 deaths occurred among 1,057 eligible patients,
      corresponding to a mortality rate (95% CI) of 1.64 (1.37, 1.96)/100 person-years.
      Leading causes of death were non-AIDS defining cancers (n=26), AIDS (n=23) and
      cardiovascular diseases (n=12). Social vulnerability (HR [95% CI] =1.2 [1.0,
      1.5]) was associated with increased mortality risk, after adjustment for other
      known behavioural and bio-medical predictors. CONCLUSIONS: Social vulnerability
      remains a major mortality predictor in ART-treated patients. A real need exists
      for innovative interventions targeting individuals cumulating several sources of
      social vulnerability, to ensure that social inequalities do not continue to lead
      to higher mortality.

PMID- 25859627
TI  - Task shifting for cataract surgery in eastern Africa: productivity and attrition
      of non-physician cataract surgeons in Kenya, Malawi and Tanzania.
AB  - BACKGROUND: This project examined the surgical productivity and attrition of non
      physician cataract surgeons (NPCSs) in Tanzania, Malawi, and Kenya. METHODS:
      Baseline (2008-9) data on training, support, and productivity (annual cataract
      surgery rate) were collected from officially trained NPCSs using mailed
      questionnaires followed by telephone interviews. Telephone interviews were used
      to collect follow-up data annually on productivity and semi-annually on
      attrition. A detailed telephone interview was conducted if a surgeon left his/her
      post. Data were entered into and analysed using STATA. RESULTS: Among the 135
      NPCSs, 129 were enrolled in the study (Kenya 88, Tanzania 38, and Malawi 3) mean
      age 42 years; average time since completing training 6.6 years. Employment was in
      District 44%, Regional 24% or mission/ private 32% hospitals. Small incision
      cataract surgery was practiced by 38% of the NPCSs. The mean cataract surgery
      rate was 188/year, median 76 (range 0-1700). For 39 (31%) NPCSs their surgical
      rate was more than 200/year. Approximately 22% in Kenya and 25% in Tanzania had
      years where the cataract surgical rate was zero. About 11% of the surgeons had no
      support staff. CONCLUSIONS: High quality training is necessary but not sufficient
      to result in cataract surgical activity that meets population needs and maintains
      surgical skill. Needed are supporting institutions and staff, functioning
      equipment and programs to recruit and transport patients.

PMID- 25859626
TI  - Cultural considerations for South Asian women with breast cancer.
AB  - PURPOSE: Cultural values shape a woman's experience of disease and introduce
      novel stressors that influence psychosocial needs and adaptation. This literature
      review examines the psychosocial impact of breast cancer in South Asian women, a
      large group that has received little attention in this regard. METHODS: We
      conducted a comprehensive review of the literature published before April 2014
      using Ovid MEDLINE, PsychINFO, PubMED, CINHAL, EMBASE, and Sociological
      Abstracts. We searched for articles about the psychosocial impact of breast
      cancer in South Asian women. We retained 23 studies for review. RESULTS: The
      literature concerning South Asian women's experiences identified culturally
      linked themes that play significant roles in shaping the illness experience;
      e.g., stigma and breast cancer, low priority of women's health, collective
      experience of disease, and religion and spirituality. CONCLUSION: There is a
      growing need for culturally sensitive care for South Asian women. By
      understanding the core cultural values and integrating them into clinical
      practice, Western healthcare providers may improve the quality of care they
      deliver and help women to extract the maximum benefit. IMPLICATIONS FOR CANCER
      SURVIVORS: Developing culturally competent support services may enhance
      effectiveness in addressing the healthcare needs of South Asian women and may
      serve other ethnic minorities in North America.

PMID- 25859629
TI  - X-ray Diffraction, Mossbauer Spectroscopy, Magnetic Susceptibility, and Specific
      Heat Investigations of Na4NpO5 and Na5NpO6.
AB  - The hexavalent and heptavalent sodium neptunate compounds Na4NpO5 and Na5NpO6
      have been investigated using X-ray powder diffraction, Mossbauer spectroscopy,
      magnetic susceptibility, and specific heat measurements. Na4NpO5 has tetragonal
      symmetry in the space group I4/m, while Na5NpO6 adopts a monoclinic unit cell in
      the space group C2/m. Both structures have been refined for the first time using
      the Rietveld method. The valence states of neptunium in these two compounds,
      i.e., Np(VI) and Np(VII), respectively, have been confirmed by the isomer shift
      values of their Mossbauer spectra. The local structural properties obtained from
      the X-ray refinements have also been related to the quadrupole coupling constants
      and asymmetry parameters determined from the Mossbauer studies. The absence of
      magnetic ordering has been confirmed for Na4NpO5. However, specific heat
      measurements at low temperatures have suggested the existence of a Schottky-type
      anomaly at around 7 K in this Np(VI) phase. 

PMID- 25859628
TI  - Arsenic Exposure and Glucose Intolerance/Insulin Resistance in Estrogen-Deficient
      Female Mice.
AB  - BACKGROUND: Epidemiological studies have reported that the prevalence of diabetes
      in women > 40 years of age, especially those in the postmenopausal phase, was
      higher than in men in areas with high levels of arsenic in drinking water. The
      detailed effect of arsenic on glucose metabolism/homeostasis in the
      postmenopausal condition is still unclear. OBJECTIVES: We investigated the
      effects of arsenic at doses relevant to human exposure from drinking water on
      blood glucose regulation in estrogen-deficient female mice. METHODS: Adult female
      mice who underwent ovariectomy or sham surgery were exposed to drinking water
      contaminated with arsenic trioxide (0.05 or 0.5 ppm) in the presence or absence
      of 17beta-estradiol supplementation for 2-6 weeks. Assays related to glucose
      metabolism were performed. RESULTS: Exposure of sham mice to arsenic
      significantly increased blood glucose, decreased plasma insulin, and impaired
      glucose tolerance, but did not induce insulin resistance. Blood glucose and
      insulin were higher, and glucose intolerance, insulin intolerance, and insulin
      resistance were increased in arsenic-treated ovariectomized mice compared with
      arsenic-treated sham mice. Furthermore, liver phosphoenolpyruvate carboxykinase
      (PEPCK) mRNA expression was increased and liver glycogen content was decreased in
      arsenic-treated ovariectomized mice compared with arsenic-treated sham mice.
      Glucose-stimulated insulin secretion in islets isolated from arsenic-treated
      ovariectomized mice was also significantly decreased. Arsenic treatment
      significantly decreased plasma adiponectin levels in sham and ovariectomized
      mice. Altered glucose metabolism/homeostasis in arsenic-treated ovariectomized
      mice was reversed by 17beta-estradiol supplementation. CONCLUSIONS: Our findings
      suggest that estrogen deficiency plays an important role in arsenic-altered
      glucose metabolism/homeostasis in females. CITATION: Huang CF, Yang CY, Chan DC,
      Wang CC, Huang KH, Wu CC, Tsai KS, Yang RS, Liu SH. 2015. Arsenic exposure and
      glucose intolerance/insulin resistance in estrogen-deficient female mice. Environ
      Health Perspect 123:1138-1144; http://dx.doi.org/10.1289/ehp.1408663.

PMID- 25859630
TI  - Development of thermosensitive hydrogels of chitosan, sodium and magnesium
      glycerophosphate for bone regeneration applications.
AB  - Thermosensitive injectable hydrogels based on chitosan neutralized with sodium
      beta-glycerophosphate (Na-beta-GP) have been studied as biomaterials for drug
      delivery and tissue regeneration. Magnesium (Mg) has been reported to stimulate
      adhesion and proliferation of bone forming cells. With the aim of improving the
      suitability of the aforementioned chitosan hydrogels as materials for bone
      regeneration, Mg was incorporated by partial substitution of Na-beta-GP with
      magnesium glycerophosphate (Mg-GP). Chitosan/Na-beta-GP and chitosan/Na-beta
      GP/Mg-GP hydrogels were also loaded with the enzyme alkaline phosphatase (ALP)
      which induces hydrogel mineralization. Hydrogels were characterized
      physicochemically with respect to mineralizability and gelation kinetics, and
      biologically with respect to cytocompatibility and cell adhesion. Substitution of
      Na-beta-GP with Mg-GP did not negatively influence mineralizability. Cell
      biological testing showed that both chitosan/Na-beta-GP and chitosan/Na-beta
      GP/Mg-GP hydrogels were cytocompatible towards MG63 osteoblast-like cells. Hence,
      chitosan/Na-beta-GP/Mg-GP hydrogels can be used as an alternative to chitosan/Na
      beta-GP hydrogels for bone regeneration applications. However the incorporation
      of Mg in the hydrogels during hydrogel formation did not bring any appreciable
      physicochemical or biological benefit. 

PMID- 25859631
TI  - Synaptic competition in the lateral amygdala and the stimulus specificity of
      conditioned fear: a biophysical modeling study.
AB  - Competitive synaptic interactions between principal neurons (PNs) with differing
      intrinsic excitability were recently shown to determine which dorsal lateral
      amygdala (LAd) neurons are recruited into a fear memory trace. Here, we explored
      the contribution of these competitive interactions in determining the stimulus
      specificity of conditioned fear associations. To this end, we used a realistic
      biophysical computational model of LAd that included multi-compartment
      conductance-based models of 800 PNs and 200 interneurons. To reproduce the
      continuum of spike frequency adaptation displayed by PNs, the model included
      three subtypes of PNs with high, intermediate, and low spike frequency
      adaptation. In addition, the model network integrated spatially differentiated
      patterns of excitatory and inhibitory connections within LA, dopaminergic and
      noradrenergic inputs, extrinsic thalamic and cortical tone afferents to simulate
      conditioned stimuli as well as shock inputs for the unconditioned stimulus. Last,
      glutamatergic synapses in the model could undergo activity-dependent plasticity.
      Our results suggest that plasticity at both excitatory (PN-PN) and di-synaptic
      inhibitory (PN-ITN and, particularly, ITN-PN) connections are major determinants
      of the synaptic competition governing the assignment of PNs to the memory trace.
      The model also revealed that training-induced potentiation of PN-PN synapses
      promotes, whereas that of ITN-PN synapses opposes, stimulus generalization.
      Indeed, suppressing plasticity of PN-PN synapses increased, whereas preventing
      plasticity of interneuronal synapses decreased the CS specificity of PN
      recruitment. Overall, our results indicate that the plasticity configuration
      imprinted in the network by synaptic competition ensures memory specificity.
      Given that anxiety disorders are characterized by tendency to generalize learned
      fear to safe stimuli or situations, understanding how plasticity of intrinsic LAd
      synapses regulates the specificity of learned fear is an important challenge for
      future experimental studies.

PMID- 25859633
TI  - Deep brain stimulation in the globus pallidus compensates response inhibition
      deficits: evidence from pantothenate kinase-associated neurodegeneration.
AB  - Fronto-striatal loops are important for many cognitive control processes, like
      response inhibition, and it has been suggested that the globus pallidus is of
      particular importance for these processes. In the current study, we investigate
      the effect of deep brain stimulation in the GP on response inhibition processes
      by means of neurophysiological (EEG) methods. We perform a case-control study in
      neuroaxonal dystrophy pantothenate kinase-associated neurodegeneration (PKAN)
      using single-case statistics. We control the signal-to-noise ratio of the EEG
      data. The data show that disease-related changes in the globus pallidus lead to
      dysfunctions in response inhibition processes. Dysfunctions in the GP seem to
      affect controlled, but not automatized behavior as evidenced by an increased rate
      of false alarms and attenuation of inhibition-related neurophysiological
      correlates. With respect to controlled behavior in terms of response inhibition,
      it seems that pre-motor subprocesses and not evaluation subprocesses are
      affected. Deep brain stimulation in the globus pallidus seems to be able to
      compensate the effects of disease-related changes in this structure and
      normalizes response inhibition performance and their electrophysiological
      correlates in PKAN.

PMID- 25859634
TI  - Instrument of self-perception and knowledge of dental erosion: cross-cultural
      adaptation to the Brazilian population.
AB  - There are few instruments available in Brazil for obtaining data on dental
      erosion among adults. For this reason, the interview entitled "A Survey on Hong
      Kong People's Dietary Behavior in Relations to Acid Erosion", published in
      English, was considered for translation. The aim of this study was to perform a
      cross-cultural adaptation and content validation for the Brazilian population.
      After obtaining the author's permission, the interview underwent several stages:
      translation, back translation, review by a bilingual person and a committee of
      experts, administration of the English instrument and of the Portuguese version
      to a bilingual group, and pretesting in a convenience sample of 50 adults. The
      interview was translated and adapted to the Portuguese language and the Brazilian
      culture. The analysis of the data revealed that the interview was easy to apply,
      conduct and understand; therefore, it was considered viable and capable of being
      used in different studies. 

PMID- 25859632
TI  - A central mesencephalic reticular formation projection to the supraoculomotor
      area in macaque monkeys.
AB  - The central mesencephalic reticular formation is physiologically implicated in
      oculomotor function and anatomically interwoven with many parts of the oculomotor
      system's premotor circuitry. This study in Macaca fascicularis monkeys
      investigates the pattern of central mesencephalic reticular formation projections
      to the area in and around the extraocular motor nuclei, with special emphasis on
      the supraoculomotor area. It also examines the location of the cells responsible
      for this projection. Injections of biotinylated dextran amine were
      stereotaxically placed within the central mesencephalic reticular formation to
      anterogradely label axons and terminals. These revealed bilateral terminal fields
      in the supraoculomotor area. In addition, dense terminations were found in both
      the preganglionic Edinger-Westphal nuclei. The dense terminations just dorsal to
      the oculomotor nucleus overlap with the location of the C-group medial rectus
      motoneurons projecting to multiply innervated muscle fibers suggesting they may
      be targeted. Minor terminal fields were observed bilaterally within the borders
      of the oculomotor and abducens nuclei. Injections including the supraoculomotor
      area and oculomotor nucleus retrogradely labeled a tight band of neurons crossing
      the central third of the central mesencephalic reticular formation at all
      rostrocaudal levels, indicating a subregion of the nucleus provides this
      projection. Thus, these experiments reveal that a subregion of the central
      mesencephalic reticular formation may directly project to motoneurons in the
      oculomotor and abducens nuclei, as well as to preganglionic neurons controlling
      the tone of intraocular muscles. This pattern of projections suggests an as yet
      undetermined role in regulating the near triad.

PMID- 25859635
TI  - Improving adhesion between luting cement and zirconia-based ceramic with an
      alternative surface treatment.
AB  - This study evaluated the influence of an alternative surface treatment on the
      microshear bond strength (MUsbs) of zirconia-based ceramic. Thirty-five zirconia
      disks were assigned to five groups according to the following treatments: Control
      (CO), glass and silane were not applied to the zirconia surface; G1, air blasted
      with 100MUm glass beads + glaze + silane; G2, a gel containing 15% (by weight)
      glass beads applied to the ceramic surface + glaze + silane; G3, a gel containing
      25% (by weight) glass beads applied to the ceramic surface + glaze + silane; and
      G4, a gel containing 50% (by weight) glass beads applied to the ceramic surface +
      glaze + silane. The specimens were built up using RelyX ARC(r), according to the
      manufacturer's recommendations, and inserted in an elastomeric mold with an inner
      diameter of 0.8 mm. The MUsbs test was performed using a testing machine at a
      crosshead speed of 0.5 mm/min. ANOVA and Tukey's test (p < 0.05) were applied to
      the bond strength values (in MPa). CO (15.6 +/- 4.1) showed the lowest MUsbs
      value. There were no statistical differences between the G1 (24.9 +/- 7.4), G2
      (24.9 +/- 2.3), G3 (35.0 +/- 10.3) and G4 (35.3 +/- 6.0) experimental groups.
      Those groups submitted to surface treatments with higher concentrations of glass
      showed a lower frequency of adhesive failures. In conclusion, the glass
      application improved the interaction between the ceramic and the luting cement. 

PMID- 25859637
TI  - Leisure boredom and adolescent risk behaviour: a systematic literature review.
AB  - There has been very little research investigating leisure boredom and risk
      behaviour among adolescents in South Africa. A systematic review of literature
      was conducted to synthesise current knowledge within the field of leisure boredom
      and risk behaviour among adolescents. An online and a hand search for relevant
      articles were conducted using keywords. This resulted in the retrieval of 25
      articles that met the inclusion criteria. It was evident that the experience of
      leisure boredom is influenced by a variety of different factors, not least of
      which is the environment or context within which adolescents are situated. A key
      finding was how few studies have focussed on leisure boredom and risk behaviour
      in adolescents, particularly in the developing world. Also, gaps in the knowledge
      basis were identified, thus providing direction for future research. The review
      focuses attention on leisure boredom as a factor contributing to risk behaviour
      in adolescents. Expanding knowledge in this area is useful for individuals and
      organisations concerned with adolescent health, education and development. 

PMID- 25859636
TI  - The natural compound chebulagic acid inhibits vascular endothelial growth factor
      A mediated regulation of endothelial cell functions.
AB  - Vascular endothelial growth factor A (VEGFA) plays an important role in tumour
      angiogenesis and its angiogenic action is mainly mediated through its VEGF
      receptor 2 (VEGFR-2). Therefore drugs targeting VEGFA/VEGFR-2 are being presently
      used in the clinics for treatment of several types of solid malignant tumours. We
      here in report that low dose of chebulagic acid (CA), a hydrolysable tannin found
      in myrobalan fruits can inhibit VEGFA induced vascular permeability, endothelial
      cell proliferation, migration, tube formation and thereby, angiogenesis by
      suppressing VEGFR-2 phosphorylation. CA may thus be an effective and useful
      natural inhibitor of VEGFA mediated angiogenesis. 

PMID- 25859638
TI  - Drop-out from parenting training programmes: a retrospective study.
AB  - OBJECTIVE: Parent training programmes are a well-established treatment approach
      for children and adolescents with disruptive behaviour disorders. However,
      dropout from treatment is a common problem that confounds research on the
      efficacy of this approach, and wastes important mental health resources. This
      study sought to further our understanding of the reasons why parents drop out of
      parent training programmes. METHOD: Nine parents of children with disruptive
      behaviour disorders who had dropped out of a parent training programme were
      interviewed to investigate why they discontinued the programme. RESULTS: Parents
      who dropped out of treatment believed that their children were more difficult
      than other children with the same disorder and may have been better suited to a
      child-focused intervention. The parents themselves had very stressful lives, with
      the majority being single mothers with little support. Dropout parents also had
      difficulty with the group context and putting strategies into place. Practical
      concerns included parking, timing of session and the length and number of
      sessions. CONCLUSIONS: The findings are discussed in terms of what modifications
      can be made to these programmes to increase retention.

PMID- 25859639
TI  - Preliminary validation of the Multi-Attitude Suicide Tendency (MAST) scale using
      a South African adolescent sample.
AB  - OBJECTIVE: The factor structure of the Multi-Attitude Suicide Tendency (MAST)
      scale was examined using a sample of non-white South African adolescents. METHOD:
      The MAST scale was administered to 205 secondary school students between 13 and
      20 years of age. RESULTS: The scale demonstrated satisfactory internal
      consistency with alpha values being in line with previous studies using the
      instrument. Factor analysis confirmed the original four-factor structure of the
      scale. Strong support was found for the Repulsion by Death (RD) and Attraction to
      Life (AL) subscales of the instrument, with moderate support for the Atttraction
      to Death (AD) and Repulsion by Life (RL) subscales. CONCLUSION: The authors
      conclude that the generalisability of the MAST can be improved by the inclusion
      of more culturally relevant items.

PMID- 25859640
TI  - Monsters in the dark and other scary things: preschoolers' self-reports.
AB  - OBJECTIVE: This study attempted to obtain normative data regarding the content
      and frequency of expressed fears of a culturally diverse group of 152 South
      African preschool children (aged 5-7 years). METHOD: The study employed four
      measuring instruments: a biographical questionnaire, the Goodenough-Harris
      Drawing Test, and individual drawings of feared objects by participants in
      conjunction with semi-structured interviews. The data analysis included
      descriptive statistics based on the themes that emerged from the children's
      drawings and interviews. RESULTS: Fear of animals was the most commonly expressed
      fear. Other high-frequency fear categories that emerged were fear of the dark,
      night and bad dreams; fantasy people; real people; and physical harm. For the
      group as a whole, the results largely support the existing body of literature.
      Participants expressed between one and nine fears (f = 429; mean = 2.8).
      CONCLUSIONS: This study contributed to a better understanding of both an under
      researched psychological phenomenon, fear, and of an under-researched target
      group of young children. This knowledge is important in order for significant
      others, such as parents and caregivers, to understand and effectively mediate
      potentially stressful experiences of young children in their respective
      capacities.

PMID- 25859642
TI  - Childhood Re-imagined: Images and Narratives of Development in Analytical
      Psychology.

PMID- 25859641
TI  - A case of effective single-session treatment for attention deficit and learning
      problems in a routine clinical practice: the value of a transdiagnostic approach
      to case formulation.
AB  - This article reports a systematic clinical case study of the psychological
      assessment and treatment of Daniel (9), a coloured South African boy with a
      diagnosis of attention deficit hyperactivity disorder (ADHD) (inattentive type).
      The case is of scientific interest because: (1) there was only a single treatment
      session, in which contingency management training was delivered to Daniel's
      parents and teacher; (2) there was evidence for the effectiveness of the
      intervention immediately and at two-year follow-up; (3) it documents the
      transportability to a South African context of an intervention developed by
      overseas research; (4) it documents the central role of case formulation in the
      delivery of effective psychological interventions; and (5) although Daniel met
      the criteria for ADHD, he also displayed symptoms of depression and social
      anxiety and the case supports the use of a transdiagnostic approach to case
      formulation. The conscientiousness with which his parents and teachers applied
      the programme was a major factor in the effectiveness of the intervention, and
      such rapid impact would not be possible where parents and teachers are
      unavailable or not co-operative. The publication of systematic case studies such
      as this one is important for the development of a local evidence-based practice
      in South Africa. 

PMID- 25859643
TI  - Moving on after childhood sexual abuse: understanding the effects and preparing
      for therapy.

PMID- 25859644
TI  - The juvenile sex offender.

PMID- 25859645
TI  - Treating traumatized children: risk, resilience and recovery.

PMID- 25859646
TI  - Papers and posters presented at the 17th Biennial Congress of the South African
      Association for Child and Adolescent Psychiatry and Allied Professions.

PMID- 25859647
TI  - Evaluation of health literacy tools for correct prescription understanding.
AB  - OBJECTIVES: To evaluate two brief health literacy prediction tools for
      understanding of a prescription label and using a drug correctly. METHODS:
      Patients who visited the Family HealthCare Pharmacy were asked to complete the
      Newest Vital Sign (NVS) and Rapid Estimate of Adult Literacy in Medicine (REALM
      R) and to interpret a prescription medication label. Each patient received a
      bottle of amoxicillin suspension with one of four prescription labels randomly
      varied in directions for frequency and amount. Patients were also asked to
      calculate the days' supply and demonstrate their ability to draw up the required
      dose using an oral syringe. RESULTS: A total of 150 patients consented to
      participate. Only the NVS score was associated with ability to fully interpret
      the label correctly. Neither tool was related to ability to draw up the correct
      amount using an oral syringe but both had some correlation to successfully
      calculating the days' supply provided. The NVS and REALM-R literacy scores had a
      modest correlation with each other. CONCLUSION: The NVS may be useful in
      predicting prescription label understanding and a patient's ability to do a
      simple dosage calculation. Neither the NVS nor the REALM-R correlated well with
      ability to draw an amount using an oral syringe correctly.

PMID- 25859648
TI  - Comparison of nickel speciation in workplace aerosol samples using sequential
      extraction analysis and X-ray absorption near-edge structure spectroscopy.
AB  - There is a pressing need to further develop speciation knowledge of Ni workplace
      aerosols as the Zatka sequential extraction method used until now to speciate
      workplace Ni exposures has limitations. Here we compare the Zatka and XANES
      methods and evaluate XANES spectroscopy as a more appropriate and accurate
      technique for identifying nickel species in workplace aerosols. XANES
      spectroscopy is capable of identifying unique Ni species in the unaltered
      samples. Our findings indicate some significant departures in speciation
      assignment between the Zatka and XANES methods. In particular, the Zatka method
      can overestimate the soluble Ni fraction and it may underestimate the sulphidic
      and metallic fractions in some samples. Of particular importance, XANES is able
      to identify component sulphidic species. This information can lead to more
      accurate exposure matrices and more refined epidemiological analysis of
      respiratory cancer causation in sulphidic Ni processing. 

PMID- 25859649
TI  - Protein-borne methionine residues as structural antioxidants in mitochondria.
AB  - Methionine is an oxidant-labile amino acid whose major oxidation products,
      methionine sulfoxides, can be readily repaired by various NADPH-dependent
      methionine sulfoxide reductases. Formally, the methionine oxidation-reduction
      circuit could act as a cellular antioxidant system, by providing a safe sink for
      oxidants that might cause much more damage if reacting otherwise. This concept is
      supported by focal experimental evidence; however, the global importance, scope
      and biochemical role of protein-borne methionine as an inbuilt macromolecular
      antioxidant have remained incompletely defined. In analyzing proteomic methionine
      usage on different levels of comparison, we find that protein methionine (i) is
      primarily an antioxidant of mitochondria, especially of the inner mitochondrial
      membrane, (ii) responds strongly to respiratory demands on an evolutionary
      timescale, (iii) acts locally, by selectively protecting its carrier protein, and
      (iv) might be utilized as a molecular predictor of aerobic metabolic rate in
      animals, to complement traditional markers like the presence of a respiratory
      pigment. Our data support the idea that proteins in need of a long lifespan or
      acting in dangerous environments may acquire massive structural alterations aimed
      at increasing their resistance to oxidation. Counterintuitively though, they
      sometimes do so by accumulating particularly labile rather than particularly
      stable building blocks, illustrating that the technical concept of cathodic
      protection is also employed by the animate nature. 

PMID- 25859650
TI  - Differential associations of circulating asymmetric dimethylarginine and cell
      adhesion molecules with metformin use in patients with type 2 diabetes mellitus
      and stable coronary artery disease.
AB  - Metformin, the drug of first choice in type 2 diabetes mellitus (T2DM), reduces
      cardiovascular (CV) morbidity and mortality in part independently of improved
      glycemic control and changes in traditional risk factors. However, there are
      discordant reports on the effects of metformin on endothelial function in T2DM.
      Our aim was to compare biochemical endothelial markers in patients with stable
      coronary artery disease (CAD) and T2DM stratified by metformin use. We studied 70
      patients (29 women, age 68 +/- 9 years) with established T2DM referred for
      elective coronary angiography owing to stable angina who were receiving a
      standard CV medication and metformin or other oral antidiabetic drugs. Exclusion
      criteria included heart failure and other relevant coexistent disorders.
      Biochemical indices of endothelial dysfunction and activation at admission were
      compared according to metformin use for at least 1 year prior to index
      hospitalization. Clinical characteristics were similar in patients receiving
      metformin (n = 40) vs. those on other oral antidiabetic agents (n = 30). Plasma
      soluble vascular cell adhesion molecule-1 (sVCAM-1) was lower (553 +/- 148 vs.
      668 +/- 170 ug/L, P = 0.004) and asymmetric dimethylarginine (ADMA) higher (0.53
      +/- 0.09 vs. 0.48 +/- 0.08 uM, P = 0.01) in subjects on metformin, which was
      maintained in multivariate analysis. Symmetric dimethylarginine, intercellular
      adhesion molecule-1, monocyte chemotactic protein-1 and E-selectin did not differ
      across the groups. The results were substantially unchanged after exclusion of
      insulin users. Thus, metformin use appears differentially associated with sVCAM-1
      and ADMA in patients with T2DM and stable CAD. Whether this observation may
      reflect different prognostic effects of these endothelial markers in diabetes
      remains to be studied.

PMID- 25859652
TI  - Fournier's Gangrene: A Summary of 10 Years of Clinical Experience.
AB  - We aimed to present our clinical experience with FG treatment. Fournier's
      gangrene (FG) is a rare but serious disease characterized by progressive necrosis
      in the genitourinary and perineal region. The retrospective study included 43
      patients. Patients were divided into 2 groups as survivors and nonsurvivors.
      Included in the analysis were data pertaining to demographics, predisposing
      factors, comorbidities, results of bacteriologic analyses, number of
      debridements, duration of treatment, FG Severity Index (FGSI) score, fecal
      diversion methods (trephine ostomy or Flexi-Seal Fecal Management System-FMS),
      and dressing methods (wet or negative aspiration system). In the nonsurvivor
      group, urea, WBC, and age were significantly higher, whereas albumin, hematocrit,
      platelet count, and length of hospital stay (LOHS) were significantly lower
      compared to the survivor group. Mean FGSI was lower in survivors in comparison
      with nonsurvivors (5.00 +/- 1.86 and 10.00 +/- 1.27, respectively; P < 0.001). We
      conclude that FGSI is an important predictor in the prognosis of FG. Vacuum
      assisted closure (VAC) should be performed in compliant patients in order to
      enhance patient comfort by reducing pain and the number of dressings. Fecal
      diversion should be performed as needed, preferably by using FMS. The trephine
      ostomy should be the method of choice in cases where an ostomy is necessary. 

PMID- 25859654
TI  - An Unusual Cause of Lumbar Radiculopathy.

PMID- 25859655
TI  - Two-dimensional zymography differentiates gelatinase isoforms in stimulated
      microglial cells and in brain tissues of acute brain injuries.
AB  - Excessive activation of gelatinases (MMP-2/-9) is a key cause of detrimental
      outcomes in neurodegenerative diseases. A single-dimension zymography has been
      widely used to determine gelatinase expression and activity, but this method is
      inadequate in resolving complex enzyme isoforms, because gelatinase expression
      and activity could be modified at transcriptional and posttranslational levels.
      In this study, we investigated gelatinase isoforms under in vitro and in vivo
      conditions using two-dimensional (2D) gelatin zymography electrophoresis, a
      protocol allowing separation of proteins based on isoelectric points (pI) and
      molecular weights. We observed organomercuric chemical 4-aminophenylmercuric
      acetate-induced activation of MMP-2 isoforms with variant pI values in the
      conditioned medium of human fibrosarcoma HT1080 cells. Studies with murine BV-2
      microglial cells indicated a series of proform MMP-9 spots separated by variant
      pI values due to stimulation with lipopolysaccharide (LPS). The MMP-9 pI values
      were shifted after treatment with alkaline phosphatase, suggesting presence of
      phosphorylated isoforms due to the proinflammatory stimulation. Similar MMP-9
      isoforms with variant pI values in the same molecular weight were also found in
      mouse brains after ischemic and traumatic brain injuries. In contrast, there was
      no detectable pI differentiation of MMP-9 in the brains of chronic Zucker obese
      rats. These results demonstrated effective use of 2D zymography to separate
      modified MMP isoforms with variant pI values and to detect posttranslational
      modifications under different pathological conditions. 

PMID- 25859656
TI  - Physiological and comparative proteomic analysis reveals different drought
      responses in roots and leaves of drought-tolerant wild wheat (Triticum
      boeoticum).
AB  - To determine the proteomic-level responses of drought tolerant wild wheat
      (Triticum boeoticum), physiological and comparative proteomic analyses were
      conducted using the roots and the leaves of control and short term drought
      stressed plants. Drought stress was imposed by transferring hydroponically grown
      seedlings at the 3-leaf stage into 1/2 Hoagland solution containing 20% PEG-6000
      for 48 h. Root and leaf samples were separately collected at 0 (control), 24, and
      48 h of drought treatment for analysis. Physiological analysis indicated that
      abscisic acid (ABA) level was greatly increased in the drought-treated plants,
      but the increase was greater and more rapid in the leaves than in the roots. The
      net photosynthetic rate of the wild wheat leaves was significantly decreased
      under short-term drought stress. The deleterious effects of drought on the
      studied traits mainly targeted photosynthesis. Comparative proteomic analysis
      identified 98 and 85 differently changed protein spots (DEPs) (corresponding to
      87 and 80 unique proteins, respectively) in the leaves and the roots,
      respectively, with only 6 mutual unique proteins in the both organs. An
      impressive 86% of the DEPs were implicated in detoxification and defense, carbon
      metabolism, amino acid and nitrogen metabolism, proteins metabolism, chaperones,
      transcription and translation, photosynthesis, nucleotide metabolism, and signal
      transduction. Further analysis revealed some mutual and tissue-specific responses
      to short-term drought in the leaves and the roots. The differences of drought
      response between the roots and the leaves mainly included that signal sensing and
      transduction-associated proteins were greatly up-regulated in the roots.
      Photosynthesis and carbon fixation ability were decreased in the leaves.
      Glycolysis was down-regulated but PPP pathway enhanced in the roots, resulting in
      occurrence of complex changes in energy metabolism and establishment of a new
      homeostasis. Protein metabolism was down-regulated in the roots, but enhanced in
      the leaves. These results will contribute to the existing knowledge on the
      complexity of root and leaf protein changes that occur in response to drought,
      and also provide a framework for further functional studies on the identified
      proteins. 

PMID- 25859657
TI  - Species distribution and population connectivity of deep-sea mussels at
      hydrocarbon seeps in the Gulf of Mexico.
AB  - Hydrocarbon seepage is widespread and patchy in the Gulf of Mexico, and six
      species of symbiont containing bathymodiolin mussels are found on active seeps
      over wide and overlapping depth and geographic ranges. We use mitochondrial genes
      to discriminate among the previously known and a newly discovered species and to
      assess the connectivity among populations of the same species in the northern
      Gulf of Mexico (GoM). Our results generally validate the morphologically based
      distribution of the three previously known GoM species of Bathymodiolus, although
      we found that approximately 10% of the morphologically based identifications were
      incorrect and this resulted in some inaccuracies with respect to their previously
      assigned depth and geographical distribution patterns. These data allowed us to
      confirm that sympatry of two species of Bathymodiolus within a single patch of
      mussels is common. A new species of bathymodiolin, Bathymodiolus sp. nov.,
      closely related to B. heckerae was also discovered. The two species live at the
      same depths but have not been found in sympatry and both have small effective
      population sizes. We found evidence for genetic structure within populations of
      the three species of Bathymodiolinae for which we had samples from multiple sites
      and suggest limited connectivity for populations at some sites. Despite
      relatively small sample sizes, genetic diversity indices suggest the largest
      population sizes for B. childressi and Tamu fisheri and the smallest for B.
      heckerae and B. sp. nov. among the GoM bathymodiolins. Moreover, we detected an
      excess of rare variants indicating recent demographic changes and population
      expansions for the four species of bathymodiolins from the Gulf of Mexico. 

PMID- 25859658
TI  - Significance of technetium-99m human serum albumin diethylenetriamine pentaacetic
      acid scintigraphy in patients with nephrotic syndrome.
AB  - It is thought that a large amount of albumin leaking from the glomerulus in
      nephrotic syndrome (NS) is reabsorbed at the proximal tubule and catabolized.
      Therefore, it is possible the final quantity of urinary protein does not always
      reflect the amount of leakage of protein from the glomerulus. We experienced two
      cases without nephrotic range proteinuria thought to involve hypoproteinemia due
      to the same pathophysiology as NS. On these patients, we performed protein
      leakage scintigraphy with technetium-99m human serum albumin diethylenetriamine
      pentaacetic acid (99mTc-HSAD) to exclude a diagnosis of protein-losing
      gastroenteropathy and observed diffuse positive accumulation in the kidneys with
      more intense uptake in the kidney than the liver on the anterior view 24 hours
      after 99mTc-HSAD administration. In healthy adults intravenously given 99mTc
      HSAD, the same dynamics are observed as in albumin metabolism, and the organ
      radioactivity of the liver and kidneys after 24 hours is equal. Therefore, we
      thought it was possible that the renal uptake 24 hours after 99mTc-HSAD
      administration was a characteristic finding of NS. In order to confirm it, the
      subjects were divided into two groups: the NS group (n = 10) and the non-NS group
      (n = 7). We defined more intense uptake in the kidney than the liver on the
      anterior view 24 hours after 99mTc-HSAD administration as Dense Kidney (+).
      Furthermore, we designed regions of interest in the right and left kidneys and
      liver on anterior and posterior images, then calculated the kidney-liver ratio.
      Nine of the ten patients had Dense Kidney (+) in the NS group, compared to none
      in the non-NS group. And the kidney-liver ratio was significantly higher in the
      NS group than in the non-NS group on each view in the bilateral kidneys. In
      conclusion, our results suggest that the renal uptake 24 hours after 99mTc-HSAD
      administration is a characteristic finding of NS. 

PMID- 25859659
TI  - Prevalence and factors associated with sexually transmitted infections among HIV
      positive women opting for intrauterine contraception.
AB  - BACKGROUND: Women living with HIV/AIDS (WLHA) are a high risk group for sexually
      transmitted infections (STIs). However, the majority of women with STIs are
      asymptomatic. Data on prevalence of STIs among WLHA in Uganda are limited. The
      objective of the study was to determine prevalence and factors associated with
      STIs among WLHA opting for intrauterine contraceptive device (IUD). METHODS:
      Three hundred fifty one WLHA deemed free of STIs using a syndromic logarithm were
      enrolled into the study. Endo-cervical swabs were taken before IUD insertion and
      PCR test for Nisseria gonorrhea (NG), Trichomonas vaginalis (TV) and Chlamydia
      trachomatis (CT) infections conducted. RESULTS: Participants' mean age was 29.4
      +/- 6.2 years, 83% were under 35years, 50% had secondary education and 73% were
      married. The majority (69%) had disclosed their HIV sero status to their spouses,
      82% used Cotrimoxazole prophylaxis, 70% were on antiretroviral therapy, 90% had
      CD4 count greater than 350, about 60% reported condoms use and 70% were of parity
      2-4. Over 50% of the participants' spouses were older than 35 years and 72% had
      attained secondary education. STIs prevalence was 11.1%, (95% CI 7.8-14.4) and
      individual prevalence for TV, NG, and CT was 5.9%, 5.4% and 0.9% respectively.
      Factors independently associated with STI were having primary or less education
      (OR= 2.3, 95% CI: 1.09 - 4.85) having a spouse of primary or less education (OR=
      3.3, 95% CI: 1.6 - 6.78) and muslim faith (OR= 0.2, 95% CI: 0.04 - 0.78).
      CONCLUSION: STI prevalence was 11.1%. TV and NG were the commonest STIs in this
      population. Having primary or less education for both participant and spouse was
      associated with increased risk while being of muslim faith was associated with
      reduced risk of STI.

PMID- 25859660
TI  - Emotion-motion interactions in conversion disorder: an FMRI study.
AB  - OBJECTIVES: To evaluate the neural correlates of implicit processing of negative
      emotions in motor conversion disorder (CD) patients. METHODS: An event related
      fMRI task was completed by 12 motor CD patients and 14 matched healthy controls
      using standardised stimuli of faces with fearful and sad emotional expressions in
      comparison to faces with neutral expressions. Temporal changes in the sensitivity
      to stimuli were also modelled and tested in the two groups. RESULTS: We found
      increased amygdala activation to negative emotions in CD compared to healthy
      controls in region of interest analyses, which persisted over time consistent
      with previous findings using emotional paradigms. Furthermore during whole brain
      analyses we found significantly increased activation in CD patients in areas
      involved in the 'freeze response' to fear (periaqueductal grey matter), and areas
      involved in self-awareness and motor control (cingulate gyrus and supplementary
      motor area). CONCLUSIONS: In contrast to healthy controls, CD patients exhibited
      increased response amplitude to fearful stimuli over time, suggesting abnormal
      emotional regulation (failure of habituation / sensitization). Patients with CD
      also activated midbrain and frontal structures that could reflect an abnormal
      behavioral-motor response to negative including threatening stimuli. This
      suggests a mechanism linking emotions to motor dysfunction in CD.

PMID- 25859662
TI  - Correction: The Arabidopsis miR472-RDR6 silencing pathway modulates PAMP- and
      effector-triggered immunity through the post-transcriptional control of disease
      resistance genes.
AB  - [This corrects the article DOI: 10.1371/journal.ppat.1003883.]. 

PMID- 25859661
TI  - Aberrant default-mode functional and structural connectivity in heroin-dependent
      individuals.
AB  - BACKGROUND: Little is known about connectivity within the default mode network
      (DMN) in heroin-dependent individuals (HDIs). In the current study, diffusion
      tensor imaging (DTI) and resting-state functional MRI (rs-fMRI) were combined to
      investigate both structural and functional connectivity within the DMN in HDIs.
      METHODS: Fourteen HDIs and 14 controls participated in the study. Structural
      (path length, tracts count, (fractional anisotropy) FA and (mean diffusivity) MD
      derived from DTI tractography)and functional (temporal correlation coefficient
      derived from rs-fMRI) DMN connectivity changes were examined in HDIs. Pearson
      correlation analysis was performed to compare the structural/functional indices
      and duration of heroin use/Iowa gambling task(IGT) performance in HDIs. RESULTS:
      HDIs had lower FA and higher MD in the tract connecting the posterior cingulate
      cortex/precuneus (PCC/PCUN) to right parahippocampal gyrus (PHG), compared to the
      controls. HDIs also had decreased FA and track count in the tract connecting the
      PCC/PCUN and medial prefrontal cortex (MPFC), as well as decreased functional
      connectivity between the PCC/PCUN and bilateral PHG and MPFC, compared to
      controls. FA values for the tract connecting PCC/PCUN to the right PHG and
      connecting PCC/PCUN to the MPFC were negatively correlated to the duration of
      heroin use. The temporal correlation coefficients between the PCC/PCUN and the
      MPFC, and the FA values for the tract connecting the PCC/PCUN to the MPFC were
      positively correlated to IGT performance in HDIs. CONCLUSIONS: Structural and
      functional connectivity within the DMN are both disturbed in HDIs. This
      disturbance progresses as duration of heroin use increases and is related to
      deficits in decision making in HDIs.

PMID- 25859663
TI  - Rapid Increases in forest understory diversity and productivity following a
      mountain pine beetle (Dendroctonus ponderosae) outbreak in pine forests.
AB  - The current unprecedented outbreak of mountain pine beetle (Dendroctonus
      ponderosae) in lodgepole pine (Pinus contorta) forests of western Canada has
      resulted in a landscape consisting of a mosaic of forest stands at different
      stages of mortality. Within forest stands, understory communities are the
      reservoir of the majority of plant species diversity and influence the
      composition of future forests in response to disturbance. Although changes to
      stand composition following beetle outbreaks are well documented, information on
      immediate responses of forest understory plant communities is limited. The
      objective of this study was to examine the effects of D. ponderosae-induced tree
      mortality on initial changes in diversity and productivity of understory plant
      communities. We established a total of 110 1-m2 plots across eleven mature
      lodgepole pine forests to measure changes in understory diversity and
      productivity as a function of tree mortality and below ground resource
      availability across multiple years. Overall, understory community diversity and
      productivity increased across the gradient of increased tree mortality. Richness
      of herbaceous perennials increased with tree mortality as well as soil moisture
      and nutrient levels. In contrast, the diversity of woody perennials did not
      change across the gradient of tree mortality. Understory vegetation, namely
      herbaceous perennials, showed an immediate response to improved growing
      conditions caused by increases in tree mortality. How this increased pulse in
      understory richness and productivity affects future forest trajectories in a
      novel system is unknown. 

PMID- 25859664
TI  - The Cryptococcus neoformans alkaline response pathway: identification of a novel
      rim pathway activator.
AB  - The Rim101/PacC transcription factor acts in a fungal-specific signaling pathway
      responsible for sensing extracellular pH signals. First characterized in
      ascomycete fungi such as Aspergillus nidulans and Saccharomyces cerevisiae, the
      Rim/Pal pathway maintains conserved features among very distantly related fungi,
      where it coordinates cellular adaptation to alkaline pH signals and micronutrient
      deprivation. However, it also directs species-specific functions in fungal
      pathogens such as Cryptococcus neoformans, where it controls surface capsule
      expression. Moreover, disruption of the Rim pathway central transcription factor,
      Rim101, results in a strain that causes a hyper-inflammatory response in animal
      infection models. Using targeted gene deletions, we demonstrate that several
      genes encoding components of the classical Rim/Pal pathway are present in the C.
      neoformans genome. Many of these genes are in fact required for Rim101
      activation, including members of the ESCRT complex (Vps23 and Snf7), ESCRT
      interacting proteins (Rim20 and Rim23), and the predicted Rim13 protease. We
      demonstrate that in neutral/alkaline pH, Rim23 is recruited to punctate regions
      on the plasma membrane. This change in Rim23 localization requires upstream ESCRT
      complex components but does not require other Rim101 proteolysis components, such
      as Rim20 or Rim13. Using a forward genetics screen, we identified the RRA1 gene
      encoding a novel membrane protein that is also required for Rim101 protein
      activation and, like the ESCRT complex, is functionally upstream of Rim23
      membrane localization. Homologs of RRA1 are present in other Cryptococcus species
      as well as other basidiomycetes, but closely related genes are not present in
      ascomycetes. These findings suggest that major branches of the fungal Kingdom
      developed different mechanisms to sense and respond to very elemental
      extracellular signals such as changing pH levels. 

PMID- 25859666
TI  - Characterization of HTT inclusion size, location, and timing in the zQ175 mouse
      model of Huntington's disease: an in vivo high-content imaging study.
AB  - Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder
      caused by a CAG trinucleotide repeat expansion in the huntingtin gene. Major
      pathological hallmarks of HD include inclusions of mutant huntingtin (mHTT)
      protein, loss of neurons predominantly in the caudate nucleus, and atrophy of
      multiple brain regions. However, the early sequence of histological events that
      manifest in region- and cell-specific manner has not been well characterized.
      Here we use a high-content histological approach to precisely monitor changes in
      HTT expression and characterize deposition dynamics of mHTT protein inclusion
      bodies in the recently characterized zQ175 knock-in mouse line. We carried out an
      automated multi-parameter quantitative analysis of individual cortical and
      striatal cells in tissue slices from mice aged 2-12 months and confirmed
      biochemical reports of an age-associated increase in mHTT inclusions in this
      model. We also found distinct regional and subregional dynamics for inclusion
      number, size and distribution with subcellular resolution. We used viral-mediated
      suppression of total HTT in the striatum of zQ175 mice as an example of a
      therapeutically-relevant but heterogeneously transducing strategy to demonstrate
      successful application of this platform to quantitatively assess target
      engagement and outcome on a cellular basis. 

PMID- 25859667
TI  - Editorial: Communicating vaccine safety - the Vienna Vaccine Safety Initiative.

PMID- 25859665
TI  - 15-deoxy-delta12,14-prostaglandin j2 inhibits osteolytic breast cancer bone
      metastasis and estrogen deficiency-induced bone loss.
AB  - Breast cancer is the major cause of cancer death in women worldwide. The most
      common site of metastasis is bone. Bone metastases obstruct the normal bone
      remodeling process and aberrantly enhance osteoclast-mediated bone resorption,
      which results in osteolytic lesions. 15-deoxy-Delta12,14-prostaglandin J2 (15d
      PGJ2) is an endogenous ligand of peroxisome proliferator-activated receptor gamma
      (PPARgamma) that has anti-inflammatory and antitumor activity at micromolar
      concentrations through PPARgamma-dependent and/or PPARgamma-independent pathways.
      We investigated the inhibitory activity of 15d-PGJ2 on the bone loss that is
      associated with breast cancer bone metastasis and estrogen deficiency caused by
      cancer treatment. 15d-PGJ2 dose-dependently inhibited viability, migration,
      invasion, and parathyroid hormone-related protein (PTHrP) production in MDA-MB
      231 breast cancer cells. 15d-PGJ2 suppressed receptor activator of nuclear factor
      kappa-B ligand (RANKL) mRNA levels and normalized osteoprotegerin (OPG) mRNA
      levels in hFOB1.19 osteoblastic cells treated with culture medium from MDA-MB-231
      cells or PTHrP, which decreased the RANKL/OPG ratio. 15d-PGJ2 blocked RANKL
      induced osteoclastogenesis and inhibited the formation of resorption pits by
      decreasing the activities of cathepsin K and matrix metalloproteinases, which are
      secreted by mature osteoclasts. 15d-PGJ2 exerted its effects on breast cancer and
      bone cells via PPARgamma-independent pathways. In Balb/c nu/nu mice that received
      an intracardiac injection of MDA-MB-231 cells, subcutaneously injected 15d-PGJ2
      substantially decreased metastatic progression, cancer cell-mediated bone
      destruction in femora, tibiae, and mandibles, and serum PTHrP levels. 15d-PGJ2
      prevented the destruction of femoral trabecular structures in estrogen-deprived
      ICR mice as measured by bone morphometric parameters and serum biochemical data.
      Therefore, 15d-PGJ2 may be beneficial for the prevention and treatment of breast
      cancer-associated bone diseases. 

PMID- 25859668
TI  - Historical aspects of immunization and vaccine safety communication.
AB  - It has been a long journey starting from the beginnings of variolation [3]
      leading up to the greatest success in the history of immunization: the
      eradication of smallpox [39]. Today, vaccines are an acknowledged important
      medical advance [40]. Nevertheless, immunization has been the subject of public
      controversy on several occasions [15, 24, 31]. This article shall provide a short
      overview of some aspects of the early stages of immunization in Western
      countries, including some examples of vaccine safety controversies in the past. 

PMID- 25859669
TI  - Risk communication of vaccines: challenges in the post-trust environment.
AB  - Highly publicised vaccine scares and recent debates about the risks suggest that
      public trust in immunisation programmes is fragile. For instance, the recent
      outbreak of Measles in Wales was the direct result of almost fifteen years of
      distrust for the MMR vaccine in the UK. This article shows how the latest science
      on risk communication will help critical actors, especially policy-makers, to
      build trust when they communicate risks to citizens and patients. The article
      offers policy advice on risk communication based on the results of three vaccines
      case studies. Five procedural principles which were developed for the UK
      government - the so-called "five As" of public risk communication are used to
      structure the discussion. Conclusions and recommendations suggest ways to move
      forward and build a two-way proactive risk communication practice. 

PMID- 25859671
TI  - Teaching vaccine safety communication to medical students and health
      professionals.
AB  - Not only the general public, but also those studying to become health
      professionals, are struggling to keep up with a growing body of evidence and
      increasingly complex information about the many different types of vaccines
      available to date. At the same time, a number of increasingly complex subjects of
      study are competing for their attention during undergraduate and graduate
      education. In many medical school curricula in German-speaking countries, the
      subject of vaccines has been entirely omitted, or is regarded a minor subtopic.
      During the studies, most medical school curricula in German-speaking countries do
      not offer obligatory courses and/ or hands-on training vaccinology in
      vaccination. In Germany, private pediatricians administer the majority of
      immunizations. Even during postgraduate training programs in pediatrics, which
      are largely hospital-based, vaccinations are rarely a topic, and vaccinology
      remains a "hobby" and a "field without lobby" lacking specific certification
      requirements. Studies of acceptance of vaccines among health professionals and
      medical students have shown that many may still have their own doubts and
      uncertainties about vaccines revealing a number of unanswered questions during
      their studies and postgraduate training. 

PMID- 25859670
TI  - The impact of the parent-physician relationship on parental vaccine safety
      perceptions.
AB  - In times of declining immunization rates among children in many countries and an
      increasing threat of potentially vaccine-preventable diseases, there is a strong
      need for new strategies to improve trust in vaccinations and acceptance of
      recommendations, especially in parents of infants and children. A survey to
      evaluate vaccination acceptance has been conducted in Vienna, Austria, based on a
      US CDC survey, applying a cross-sectional approach with districts and public as
      well as private kindergartens and preschools as selection base. The survey aimed
      to investigate the impact of parent satisfaction with, and overall trust in the
      physician on vaccine acceptance, as well as the impact of quality and
      completeness of safety information delivered during the vaccination consultation.
      Overall 1101 parents, predominantly (84.2%) mothers, participated in the survey.
      The majority (82.7%) of participants had a generally positive view concerning
      childhood vaccination. However, 25.1% refused at least one of the recommended
      vaccinations. In multivariate analysis, confidence in vaccinations was
      significantly influenced by education (lower confidence at higher levels of
      education), gender (higher confidence in females), and positively associated with
      trust in physician, smooth vaccination procedure, and information about vaccine
      risks. Similar results were obtained for compliance with recommended vaccinations
      with information about vaccine benefits being the most important predictor. This
      large survey indicates an important role of the physician in communicating
      balanced information about benefits and risks associated with childhood
      vaccinations. A trustworthy parent-physician relationship is crucial for
      vaccination decisions of parents. 

PMID- 25859672
TI  - The importance of precise documentation of vaccination by physicians and vaccine
      providers.
AB  - When reporting adverse events following immunisation, information about which
      vaccine was given, how it was administered, and if it was administered within the
      expiry date is often incomplete. To improve immunisation practice, a standardised
      uniform procedure is needed. Examples are given, where immunisations were given
      beyond the expiry date or were wrongly administered. These examples include
      proposals to avoid misleading documentation in the immunisation card. 

PMID- 25859673
TI  - A design thinking approach to effective vaccine safety communication.
AB  - The highly complex and controversial topic of vaccine safety communication
      warrants innovative, user-centered solutions that would start with gaining mutual
      respect while taking into account the needs, concerns and underlying motives of
      patients, parents and physicians. To this end, a non-profit collaborative project
      was conducted by The Vienna Vaccine Safety Initiative, an international think
      tank aiming to promote vaccine safety research and communication, and the School
      of Design Thinking in Potsdam, Germany, the first school for innovation in
      Europe. The revolutionary concept of the Design Thinking approach is to group
      students in small multi-disciplinary teams. As a result they can generate ground
      breaking ideas by combining their expertise and different points of view. The
      team agreed to address the following design challenge question: "How might we
      enable physicians to encourage parents and children to prevent infectious
      diseases?" The current article describes, step-by step, the ideation and
      innovation process as well as first tangible outcomes of the project. 

PMID- 25859674
TI  - Controlled language and information on vaccines: application to package inserts.
AB  - Any ambiguity in texts used in the communication about vaccines can not only
      interfere with comprehension, but also generate safety and liability issues.
      Within a survey on the quality of written protocols for at-risk interventional
      procedures and sanitary crises, we analyzed documents relating to vaccination,
      and among them, the "package-leaflet" of an anti-H1N1 influenza vaccine, widely
      disseminated to the public in 2009-2010. Among the most common mistakes, we
      observed that 1) language was not always adjusted to the non-specialist's level
      of knowledge; 2) chronology, logic, consistency, and homogeneity were often
      missing; 3) crucial pieces of information were disseminated all over the text, 4)
      use of the passive voice did not distinguish between instructions and
      information; 5) use of synonyms could be misleading and impair translation. We
      propose the use of "Controlled language" (CL) to improve the situation. By
      constraining lexicon, grammar and syntax, CL is a way to write documents that are
      clear, accurate and devoid of ambiguity. However, the set of rules necessary to
      write in CL is difficult to memorize. We thus developed authoring software
      (Redacticiel Prolipsia) to make the creation of a CL by linguists and its use by
      health professionals easy and adapted to any domain. It may considerably improve
      the writing of vaccine package inserts/leaflets. It could be used to write
      information documents about vaccines and their safety, and operating procedures
      for professionals to prepare, store, and administer vaccines, decide upon proper
      indication of vaccines, and follow patients after vaccine injection. 

PMID- 25859675
TI  - Importance of Vaccine Safety in Children with Chronic Conditions--Experience at
      the Scientific Centre for Children's Health in Moscow, Russia.
AB  - The risk of severe disease outcomes and complications of infectious diseases
      remains markedly increased in children and adolescents with chronic conditions.
      Specialized pediatric healthcare aims to improve quality of life in this high
      risk group. One of the most important measures to achieve this goal is to improve
      immunization rates in this vulnerable population. This article aims to provide
      insight into models for the integration of infectious disease prevention into
      specialized healthcare for children with chronic conditions, by the example of
      the Department of Vaccines and Disease Prevention in Children with Chronic
      Conditions in Moscow, Russian Federation. The article highlights the importance
      of vaccine safety and effectiveness research in children with chronic conditions.
      Useful strategies for the optimization of vaccination rates in this population
      are presented, along with suggestions for the development of individual
      immunization schedules for different disease conditions. 

PMID- 25859676
TI  - Communicating vaccine safety during the development and introduction of vaccines.
AB  - Vaccines are the best defense available against infectious diseases. Vaccine
      safety is of major focus for regulatory bodies, vaccine manufacturers, public
      health authorities, health care providers and the public as vaccines are often
      given to healthy children and adults as well as to pregnant woman. Safety
      assessment is critical at all stages of vaccine development. Effective, clear and
      consistent communication of the risks and benefits of vaccines and advocacy
      during all stages of clinical research (including the preparation, approvals,
      conduct of clinical trials through the post marketing phase) is critically
      important. This needs to be done for all major stakeholders (e.g. community
      members, Study Team, Health Care Providers, Ministry of Health, Regulators,
      Ethics Committee members, Public Health Authorities and Policy Makers). Improved
      stakeholder alignment would help to address some of the concerns that may affect
      the clinical research, licensing of vaccines and their wide-spread use in
      immunization programs around the world. 

PMID- 25859677
TI  - Vaccine safety monitoring systems in developing countries: an example of the
      Vietnam model.
AB  - Only few health intervention programs have been as successful as vaccination
      programs with respect to preventing morbidity and mortality in developing
      countries. However, the success of a vaccination program is threatened by rumors
      and misunderstanding about the risks of vaccines. It is short-sighted to plan the
      introduction of vaccines into developing countries unless effective vaccine
      safety monitoring systems are in place. Such systems that track adverse events
      following immunization (AEFI) is currently lacking in most developing countries.
      Therefore, any rumor may affect the entire vaccination program. Public health
      authorities should implement the safety monitoring system of vaccines, and
      disseminate safety issues in a proactive mode. Effective safety surveillance
      systems should allow for the conduct of both traditional and alternative
      epidemiologic studies through the use of prospective data sets. The vaccine
      safety data link implemented in Vietnam in mid-2002 indicates that it is feasible
      to establish a vaccine safety monitoring system for the communication of vaccine
      safety in developing countries. The data link provided the investigators an
      opportunity to evaluate AEFI related to measles vaccine. Implementing such
      vaccine safety monitoring system is useful in all developing countries. The
      system should be able to make objective and clear communication regarding safety
      issues of vaccines, and the data should be reported to the public on a regular
      basis for maintaining their confidence in vaccination programs. 

PMID- 25859678
TI  - Communicating vaccine safety in the context of immunization programs in low
      resource settings.
AB  - Vaccines are effective in preventing infectious diseases and their complications,
      hence reducing morbidity and infectious disease mortaity. Successful immunization
      programs, however, depend on high vaccine acceptance and coverage rates. In
      recent years there has been an increased level of public concern towards real or
      perceived adverse events associated with immunizations, leading to many people in
      high- as well as low-resource settings to refuse vaccines. Health care workers
      therefore must be able to provide parents and guardians of children with the most
      current and accurate information about the benefits and risks of vaccination.
      Communicating vaccine safety using appropriate channels plays a crucial role in
      maintaining public trust and confidence in vaccination programs. Several factors
      render this endeavor especially challenging in low-resource settings where
      literacy rates are low and access to information is often limited. Many languages
      are spoken in most countries in low-resource settings, making the provision of
      appropriate information difficult. Poor infrastructure often results in
      inadequate logistics. Recently, some concerned consumer groups have been able to
      propagate misinformation and rumors. To successfully communicate vaccine safety
      in a resource limited setting it is crucial to use a mix of communication
      channels that are both culturally acceptable and effective. Social mobilization
      through cultural, administrative and political leaders, the media or text
      messages (SMS) as well as the adoption of the Village Health Team (VHT) strategy
      whereby trained community members (Community Health Workers (CHWs)) are providing
      primary healthcare, can all be effective in increasing the demand for
      immunization. 

PMID- 25859679
TI  - The need to teach vaccine safety to basic scientists and public health officials.
AB  - Vaccination has been shown to be the most successful measure in preventing
      millions of mortalities and morbidities related to infectious diseases. Higher
      rates of vaccination lead to a greater number of protected individuals in the
      community. While vaccine safety is a primary concern, misinformation accessed
      through various communication channels can lead to misconceptions about
      vaccination that are often hard to address. When the public collects information,
      they usually do not check for accuracy. To overcome the problem, the most
      effective way is to disseminate information through teaching facts about vaccine
      benefits and harms to the public and the authorities in advance. To encourage the
      public to participate and support vaccination programs, basic scientists and
      public health officials must be trained and updated about vaccines and
      vaccination benefits and harms to be able to inform the public. 

PMID- 25859680
TI  - Communicating vaccine safety to the media and general public.
AB  - Vaccines are among the most effective measures to control and prevent infectious
      diseases. Yet, the topic of vaccination is difficult to communicate, as it bears
      upon individual versus common good. The efficacy and safety of vaccines can only
      be shown by the absence of undesired events, such as vaccine-preventable diseases
      or adverse events following immunization. The authors of this paper view
      accurate, transparent and timely vaccine-safety communication to the media and
      general public as a core responsibility of healthcare providers. The authors wish
      to explore potential difficulties faced by immunization specialists when talking
      to the media, and suggest how to successfully convey vaccination messages to the
      general public. 

PMID- 25859681
TI  - Why some messages speak better: child immunization in the news and on the
      internet.
AB  - Modern health protection generally affords vaccination against infectious
      diseases along with other environmental health threats. However, with the
      increase both in development of new vaccines and in making more and more vaccines
      available to the general public comes an increase in health scares, mainly in the
      media. In the wake of health scares, we often find government and health
      organizations launching campaigns to restore faith in current vaccine policies.
      But health scares are hard to quell and seem to have messages that "speak better"
      to those unconvinced about the safety of vaccines. This paper seeks to review
      recent studies on the health messages prevalent in various news outlets and on
      the internet. Equal focus has been given to messages originating from government
      and health organizations as well as those that stem from lay organizations, such
      as parent communities and anti-vaccination groups. Particular emphasis was placed
      on studies that did not simply look at the content of the message, but which
      explored the rhetoric of the message. This review revealed that there is a
      shortage of studies, and that a comprehensive study of health messages and
      communication outlets across a much wider range of vaccines is urgently
      warranted. Based on current research, lay-based/lay-oriented dissemination
      approaches seem to have a greater effect on lay perceptions of vaccines, and
      potentially parent behavior. In terms of content, these approaches rely heavily
      on parent stories around adverse effects, and in terms of rhetoric, the language
      used tends towards dread words. 

PMID- 25859682
TI  - Isoniazid induced convulsions at therapeutic dose in an alcoholic and smoker
      patient.
AB  - We report a case of isoniazid induced convulsions in 35 years old male alcoholic
      and smoker patient receiving intensive phase therapy for pulmonary tuberculosis.
      A case was confirmed by accidental positive de-challenge and rechallenge as well
      as ruled out other conditions. Use of isoniazid in alcoholic and smoker patient
      required a caution for prevention of neurological adverse reactions. Pyridoxine
      should always be prescribed to such patients for the prevention of such adverse
      reaction. 

PMID- 25859684
TI  - Axial Globe Length in Congenital Ptosis.
AB  - PURPOSE: To compare axial globe length between affected and unaffected sides in
      patients with unilateral congenital ptosis. METHODS: This prospective
      observational study included 37 patients (age range: 7 months to 58 years). The
      axial globe length, margin reflex distance-1 (MRD-1), and refractive power were
      measured. The axial globe length difference was calculated by subtracting the
      axial globe length on the unaffected side from that of the affected side. The
      relationships among axial globe length differences, MRD-1 on the affected sides,
      and patient ages were analyzed using multiple regression analysis. RESULTS: No
      significant differences were found in the axial globe length between sides (P =
      .677). The axial globe length difference was 0.17 +/- 0.30 mm (mean +/- standard
      deviation), and two patients (5.4%), aged 32 to 57 years, showed axial globe
      length more than 0.67 mm longer (corresponding to a refractive power of 2
      diopters) on the affected side compared to the unaffected side. The multiple
      regression model between axial globe length difference, patient age, and MRD-1 on
      the affected sides was less appropriate (YAGL = 0.003XAGE-0.048XMRD-1 +0.112; r =
      0.338; adjusted r2 = 0.062; P = .127). The cylindrical power was greater on the
      affected side (P = .046), although the spherical power was not different between
      sides (P = .657). CONCLUSIONS: No significant difference was identified in the
      axial globe length between sides, and only 5% of non-pediatric patients showed an
      axial globe length more than 0.67 mm longer on the affected side. Congenital
      ptosis may have little effect on axial globe length elongation, and the risk of
      axial myopia-induced anisometropic amblyopia may be low in patients with
      unilateral congenital ptosis.

PMID- 25859685
TI  - Spectral-Domain OCT Analyses of Macular Changes After Ranibizumab Therapy for
      Type 1 Retinopathy of Prematurity.
AB  - PURPOSE: To investigate the clinical and macular spectral-domain optical
      coherence tomography (SD-OCT) findings after intravitreal ranibizumab treatment
      for type 1 retinopathy of prematurity (ROP). METHODS: Eighteen eyes of 10
      premature infants with type 1 ROP were retrospectively studied. All eyes were
      treated with intravitreal ranibizumab as monotherapy. Macular SD-OCT was
      performed before and after intravitreal ranibizumab therapy using a portable SD
      OCT machine; the follow-up images were taken 1 day, 1 week, 1 month, and 2 months
      after therapy. RESULTS: Among the 10 infants, there were six males and four
      females. Mean central foveal thickness before and 2 months after intravitreal
      ranibizumab was 292.5 +/- 61.4 and 171.6 +/- 21.7 um, respectively. Differences
      were statistically significant (P = .01). Sixteen eyes of eight patients had
      macular edema before treatment. Two eyes of two patients developed a crack in the
      outer hyperreflective line on SD-OCT corresponding with retinal pigment
      epithelium with serous retinal detachment 1 day after treatment. Macular edema
      regressed in all patients 2 months after intravitreal ranibizumab therapy. Mean
      follow-up time was 11.4 +/- 1.5 months. No recurrence was seen except in both
      eyes of one patient treated with intravitreal ranibizumab monotherapy.
      CONCLUSIONS: Intravitreal ranibizumab injection is effective for the treatment of
      type 1 ROP as a monotherapy agent; however, macular changes not seen with
      indirect ophthalmoscope may develop.

PMID- 25859683
TI  - Fluctuations of serum neuron specific enolase and protein S-100B concentrations
      in relation to the use of shunt during carotid endarterectomy.
AB  - OBJECTIVE: To evaluate the changes in serum neuron specific enolase and protein S
      100B, after carotid endarterectomy performed using the conventional technique
      with routine shunting and patch closure, or eversion technique without the use of
      shunt. MATERIALS AND METHODS: Prospective non-randomized study included 43
      patients with severe (>80%) carotid stenosis undergoing carotid endarterectomy in
      regional anesthesia. Patients were divided into two groups: conventional
      endarterectomy with routine use of shunt and Dacron patch (csCEA group) and
      eversion endarterectomy without the use of shunt (eCEA group). Protein S-100B and
      NSE concentrations were measured from peripheral blood before carotid clamping,
      after declamping and 24 hours after surgery. RESULTS: Neurologic examination and
      brain CT findings on the first postoperative day did not differ from preoperative
      controls in any patients. In csCEA group, NSE concentrations decreased after
      declamping (P<0.01), and 24 hours after surgery (P<0.01), while in the eCEA group
      NSE values slightly increased (P=ns), accounting for a significant difference
      between groups on the first postoperative day (P=0.006). In both groups S-100B
      concentrations significantly increased after declamping (P<0.05), returning to
      near pre-clamp values 24 hours after surgery (P=ns). Sub-group analysis revealed
      significant decline of serum NSE concentrations in asymptomatic patients shunted
      during surgery after declamping (P<0.05) and 24 hours after surgery (P<0.01),
      while no significant changes were noted in non-shunted patients (P=ns). Decrease
      of NSE serum levels was also found in symptomatic patients operated with the use
      of shunt on the first postoperative day (P<0.05). Significant increase in NSE
      serum levels was recorded in non-shunted symptomatic patients 24 hours after
      surgery (P<0.05). CONCLUSION: Variations of NSE concentrations seemed to be
      influenced by cerebral perfusion alterations, while protein S-100B values were
      unaffected by shunting strategy. Routine shunting during surgery for symptomatic
      carotid stenosis may have the potential to prevent postoperative increase of
      serum NSE levels, a potential marker of brain injury.

PMID- 25859687
TI  - Fearbola.

PMID- 25859686
TI  - An Assessment of Participatory Integrated Vector Management for Malaria Control
      in Kenya.
AB  - BACKGROUND: The World Health Organization (WHO) recommends integrated vector
      management (IVM) as a strategy to improve and sustain malaria vector control.
      However, this approach has not been widely adopted. OBJECTIVES: We
      comprehensively assessed experiences and findings on IVM in Kenya with a view to
      sharing lessons that might promote its wider application. METHODS: The assessment
      used information from a qualitative external evaluation of two malaria IVM
      projects implemented between 2006 and 2011 and an analysis of their accumulated
      entomological and malaria case data. The project sites were Malindi and Nyabondo,
      located in coastal and western Kenya, respectively. The assessment focused on
      implementation of five key elements of IVM: integration of vector control
      methods, evidence-based decision making, intersectoral collaboration, advocacy
      and social mobilization, and capacity building. RESULTS: IVM was more
      successfully implemented in Malindi than in Nyabondo owing to greater community
      participation and multistakeholder engagement. There was a significant decline in
      the proportion of malaria cases among children admitted to Malindi Hospital, from
      23.7% in 2006 to 10.47% in 2011 (p < 0.001). However, the projects' operational
      research methodology did not allow statistical attribution of the decline in
      malaria and malaria vectors to specific IVM interventions or other factors.
      CONCLUSIONS: Sustaining IVM is likely to require strong participation and support
      from multiple actors, including community-based groups, non-governmental
      organizations, international and national research institutes, and various
      government ministries. A cluster-randomized controlled trial would be essential
      to quantify the effectiveness and impact of specific IVM interventions, alone or
      in combination. CITATION: Mutero CM, Mbogo C, Mwangangi J, Imbahale S, Kibe L,
      Orindi B, Girma M, Njui A, Lwande W, Affognon H, Gichuki C, Mukabana WR. 2015. An
      assessment of participatory integrated vector management for malaria control in
      Kenya. Environ Health Perspect 123:1145-1151;
      http://dx.doi.org/10.1289/ehp.1408748.

PMID- 25859688
TI  - Detecting residual fluorine 18 from a medical PET-CT procedure during population
      whole body counter screening in Fukushima.

PMID- 25859689
TI  - Perceptions of the utility and acceptability of an emergency child minding
      service for health staff.
AB  - OBJECTIVE: Tropical Cyclone Yasi in North Queensland activated the disaster
      management plans at The Townsville Hospital, including the establishment of an
      emergency child minding service to facilitate the return of staff to work.
      METHODS: This report describes the establishment of this service and the results
      of brief electronic surveys that were distributed in the 2 weeks following the
      cyclone to gather feedback from staff who had placed their children in the care
      of the service (consumers), staff who had manned the service (staff), and allied
      health managers whose staff had manned the service (managers). RESULTS: Overall,
      approximately 94 episodes of care were provided by the child minding service. All
      consumers responded "'yes'" in answer to the question of whether the emergency
      child minding service facilitated their return to work in the immediate post
      disaster period. The survey also identified that a lack of effective advertising
      may have prevented further uptake of the child minding service. CONCLUSIONS: The
      provision of an emergency child minding service facilitated the return to work of
      health care staff immediately after Tropical Cyclone Yasi. More research is
      needed to understand the effect disaster type has on the uptake of a child
      minding service.

PMID- 25859690
TI  - Assessing electronic death registration and american red cross systems for
      mortality surveillance during Hurricane Sandy, October 29-November 10, 2012, New
      York City.
AB  - OBJECTIVE: We briefly describe 2 systems that provided disaster-related mortality
      surveillance during and after Hurricane Sandy in New York City, namely, the New
      York City Health Department Electronic Death Registration System (EDRS) and the
      American Red Cross paper-based tracking system. METHODS: Red Cross fatality data
      were linked with New York City EDRS records by using decedent name and date of
      birth. We analyzed cases identified by both systems for completeness and
      agreement across selected variables and the time interval between death and
      reporting in the system. RESULTS: Red Cross captured 93% (41/44) of all Sandy
      related deaths; the completeness and quality varied by item, and timeliness was
      difficult to determine. The circumstances leading to death captured by Red Cross
      were particularly useful for identifying reasons individuals stayed in evacuation
      zones. EDRS variables were nearly 100% complete, and the median interval between
      date of death and reporting was 6 days (range: 0-43 days). CONCLUSIONS: Our
      findings indicate that a number of steps have the potential to improve disaster
      related mortality surveillance, including updating Red Cross surveillance forms
      and electronic databases to enhance timeliness assessments, greater collaboration
      across agencies to share and use data for public health preparedness, and
      continued expansion of electronic death registration systems.

PMID- 25859691
TI  - Developing strong response capacity: training volunteers in the medical reserve
      corps.
AB  - OBJECTIVE: The success of the Medical Reserve Corps (MRC) is dependent on the
      ability of volunteers to respond in a timely and effective manner. This study
      aimed to assess the current status of MRC volunteer training and to examine the
      association between MRC characteristics and provision of training. METHODS: The
      data for this study were drawn from the 2013 Network Profile Survey of the MRC,
      which was administered to active MRC unit leaders or designated alternates of 962
      units across the country in April to May of 2013. RESULTS: Over 80% of MRCs had a
      training plan. Ninety-one percent of MRCs offered one or more training courses to
      volunteers, and 73% indicated requirements for mandatory training. Approximately
      84% of MRC units collaborated with other organizations to conduct trainings.
      Units with more volunteers (>150) were 3 times as likely to have a plan for
      volunteer training as were those with fewer volunteers (<=50). Compared to units
      with a full-time leader, those with leaders who were volunteers were only 0.57
      times as likely to have a training plan. CONCLUSIONS: An overwhelming majority of
      MRC units provide critical training to their volunteers prior to an emergency
      deployment. To further strengthen the overall MRC capacities, it is important for
      MRC units to have a training plan tailored to their community needs and features,
      make full use of available training resources, and collaborate with partner
      organizations.

PMID- 25859692
TI  - Educating first responders to provide emergency services to individuals with
      disabilities.
AB  - OBJECTIVE: Individuals with disabilities experience more negative outcomes due to
      natural and manmade disasters and emergencies than do people without
      disabilities. This vulnerability appears to be due in part to knowledge gaps
      among public health and safety emergency planning and response personnel
      (responders). We assessed the effectiveness of an online program to increase
      emergency responder knowledge about emergency planning and response for
      individuals with disabilities. METHODS: Researchers developed an online course
      designed to teach public health, emergency planning and management, and other
      first response personnel about appropriate, efficient, and equitable emergency
      planning, response, interaction, and communication with children and adults with
      disabilities before, during, and after disasters or emergencies. Course features
      included an ongoing storyline, exercises embedded in the form of real-life
      scenarios, and game-like features such as points and timed segments. RESULTS:
      Evaluation measures indicated significant pre- to post-test gains in learner
      knowledge and simulated applied skills. CONCLUSION: An online program using
      scenarios and simulations is an effective way to make disability-related training
      available to a wide variety of emergency responders across geographically
      disparate areas.

PMID- 25859694
TI  - Amyotrophic lateral sclerosis mortality rates in Chile: A population based study
      (1994-2010).
AB  - Our objective was to describe amyotrophic lateral sclerosis (ALS) mortality rates
      in the Chilean population over a 17-year period. Chilean death records (1994
      2010) were reviewed for the ICD-10 diagnosis G.12.2 (including motor neuron
      disease and similar conditions), and weighted with population data. Crude and
      standardized mortality rates by ALS were calculated at the nationwide level and
      by geographic zone. A risk analysis was performed in successive cohorts from 1910
      1919 to 1960-1969, comparing mortality slopes. One thousand six hundred and
      seventy-one deaths were recorded during 1994-2010, with an average of 1.13 per
      100,000, a 1.2:1 male/female ratio, and a statistically significant increase in
      mortality rate. According to geographical distribution, the Austral area, with a
      larger population of European origin, showed higher mortality rates compared to
      the national average. The cohort analysis showed an increasing risk of dying from
      ALS for all cohorts, and highest above 64 years of age, becoming a competitive
      cause of death in older ages. In conclusion, as expected, the mortality rate in
      Chile by ALS is higher than that reported previously in our country, and similar
      to other Latin American countries. ALS mortality rate has increased over time
      probably due to the aging of the population and decline in rates for competing
      causes of death. 

PMID- 25859695
TI  - Contested multiple voices of young masculinities amongst adolescent boys in
      Alexandra Township, South Africa.
AB  - OBJECTIVE: In this paper, the author explores how adolescent boys negotiate
      multiple voices of masculinity in Alexandra Township, a historically working
      class and black community in Gauteng, South Africa. METHOD: Thirty adolescent
      boys were recruited and provided with disposable cameras to take 27 photos under
      the theme 'my life as a boy' in the new South Africa. Arrangements were made for
      photos to be collected and processed. In the follow-up interviews, boys were
      asked to give a description of each photo and why and how they had decided to
      take that photo to represent aspects of their masculinity. Results Some of the
      photos taken depict books, cars, boys smoking, gambling, fighting and reading
      books at school. CONCLUSION: This study reveals that being a boy is not a
      homogeneous phenomenon. All the participants agreed that there are different ways
      of being a boy and that some boys are more popular than others, which often
      depends on the context in which the boys find themselves. The interviews revealed
      recurring allusions to different 'types' of boys at schools in Alexandra Township
      namely, tsotsi boys and academic boys. However, it is important to note that boys
      do not fit neatly into each of these categories. The findings of the study reveal
      some interesting complexities on how adolescent boys simultaneously accept and
      reject certain practices of township masculinity in their daily lives, depending
      on the time and space in which they find themselves. Some positions are more
      dominant than others and this reveals how adolescent boys 'police' each other as
      part of a process of conforming to idealised norms of township masculinity as
      lived out in the township context of Alexandra.

PMID- 25859693
TI  - Systemic Metabolomic Changes in Blood Samples of Lung Cancer Patients Identified
      by Gas Chromatography Time-of-Flight Mass Spectrometry.
AB  - Lung cancer is a leading cause of cancer deaths worldwide. Metabolic alterations
      in tumor cells coupled with systemic indicators of the host response to tumor
      development have the potential to yield blood profiles with clinical utility for
      diagnosis and monitoring of treatment. We report results from two separate
      studies using gas chromatography time-of-flight mass spectrometry (GC-TOF MS) to
      profile metabolites in human blood samples that significantly differ from non
      small cell lung cancer (NSCLC) adenocarcinoma and other lung cancer cases.
      Metabolomic analysis of blood samples from the two studies yielded a total of 437
      metabolites, of which 148 were identified as known compounds and 289 identified
      as unknown compounds. Differential analysis identified 15 known metabolites in
      one study and 18 in a second study that were statistically different (p-values
      <0.05). Levels of maltose, palmitic acid, glycerol, ethanolamine, glutamic acid,
      and lactic acid were increased in cancer samples while amino acids tryptophan,
      lysine and histidine decreased. Many of the metabolites were found to be
      significantly different in both studies, suggesting that metabolomics appears to
      be robust enough to find systemic changes from lung cancer, thus showing the
      potential of this type of analysis for lung cancer detection. 

PMID- 25859696
TI  - The Alcohol Use Disorders Identification Scale (AUDIT) normative scores for a
      multiracial sample of Rhodes University residence students.
AB  - OBJECTIVE: The objective of this research is to obtain accurate drinking norms
      for students living in the university residences in preparation for future social
      norms interventions that would allow individual students to compare their
      drinking to an appropriate reference group. METHOD: Random cluster sampling was
      used to obtain data from 318 residence students who completed the Alcohol Use
      Disorders Identification Test (AUDIT), a brief, reliable and valid screening
      measure designed by the World Health Organisation (Babor et al. 2001). RESULTS:
      The Cronbach alpha coefficient of 0.83 reported for this multicultural sample is
      high, suggesting that the AUDIT may be reliably used in this and similar
      contexts. Normative scores are reported in the form of percentiles. Comparisons
      between the portions of students drinking safely and hazardously according to
      race and gender indicate that while male students are drinking no more
      hazardously than female students, white students drink far more hazardously than
      black students. CONCLUSIONS: These differences suggest that both race- and gender
      specific norms would be essential for an effective social norms intervention in
      this multicultural South African context. Finally, the racialised drinking
      patterns might reflect an informal segregation of social space at Rhodes
      University.

PMID- 25859697
TI  - Psychosocial adjustment of children affected by HIV/AIDS in Ghana.
AB  - OBJECTIVE: The study was conducted to assess the psychosocial adjustment of
      children affected by HIV/ AIDS in the eastern part of Ghana. METHOD: Four groups
      of children (children who lost their parents to AIDS, children who lost their
      parents through other causes, children living with HIV infected, alive parents
      and the comparison children who were from the same community but did not have
      HIV/AIDS-related illness or death in their families) were interviewed on
      depressive symptoms, prosocial behaviours, hyperactivity, conduct and peer
      problems using the Strengths and Difficulties Questionnaire (SDQ). RESULTS:
      Orphans in general and children living with HIV-infected parents consistently
      demonstrated poorer psychosocial adjustment than comparison children in the same
      community. CONCLUSION: The findings underscore the urgency and importance of
      culturally and developmentally appropriate intervention efforts targeting
      psychosocial problems among children affected by AIDS and call for more
      exploration of risk and resilience factors, both individual and contextual,
      affecting the wellbeing of these children.

PMID- 25859698
TI  - A description of the establishment of a new child and adolescent mental health
      service in the United Kingdom.
AB  - OBJECTIVE: This paper describes an evaluation of a child and adolescent mental
      health project located in a large County in Eastern England. The project was one
      of eight developed in the voluntary sector and supported by the UK Mental Health
      Foundation as part of a national initiative aimed at responding in new,
      accessible ways to young people requiring help for emotional and mental health
      problems. METHODS: This was a mixed-method study conducted with referring
      agencies and service users and staff at the project using individual face to face
      semi-structured interviews, a focus group and postal questionnaires. Core
      evaluation questions were based on the UK Commission for Health Improvement (CHI)
      evaluation instrument for child and adolescent mental health service provision
      (DOH 2003a). RESULTS: Over the course of three years, 494 referrals were
      received. A total of 25% of questionnaires were returned from the referring
      agencies. A representative sample of clients and project staff were interviewed
      and audio-tape recorded. Clients reported overall satisfaction with the service
      provided feeling it was accessible, acceptable and appropriate. Staff enjoyed
      working outside statutory contexts but desired more stable funding arrangements
      to enable the project to expand. CONCLUSIONS: The evidence from this study
      demonstrates that it is possible to establish, with careful planning,
      interprofessional teams who are able to integrate with primary care and
      specialist child and adolescent mental health staff, within the social
      environments of children and families to provide a more accessible and acceptable
      service.

PMID- 25859699
TI  - The parent-child-therapist alliance: A case study using a strategic approach.
AB  - In this paper we present a single case study of a clinical approach that
      addresses the needs of parents and their children in psychotherapy. The approach
      begins by addressing the child's and parent's concerns separately at first by
      establishing strong therapeutic alliances with each, and then proceeds to address
      the concerns of the parent-child dyad. The basic premise is that the therapeutic
      alliance is the central element to successful outcomes in psychotherapy. The
      nature of alliance-building and its associated methods and techniques have been
      extensively considered for adult therapy. However, there is considerably less
      written on the therapeutic alliance with children and adolescents in the context
      of family interventions. We briefly examine some theoretical dimensions and
      applications of the therapeutic alliance in psychotherapy with
      children/adolescents and their parents. A three-phase alliance-building
      psychotherapy strategy, founded on the idea that each therapeutic relationship
      warrants an effective working alliance, is proposed. The case of a single mother
      and her adolescent daughter is employed to illustrate the strategy. 

PMID- 25859700
TI  - Handbook of infant mental health (Third edition).

PMID- 25859701
TI  - Relational trauma in infancy: psychoanalytic, attachment and neuropsychological
      contributions to parent-infant psychotherapy.

PMID- 25859702
TI  - Behavioural and emotional disorders in adolescents: nature, assessment, and
      treatment.

PMID- 25859703
TI  - Straight talk about psychiatric medications for kids (Third edition).

PMID- 25859704
TI  - Increased self-efficacy following a ten-day developmental voyage.

PMID- 25859705
TI  - Journal abstracts from current research in the field of child and adolescent
      mental health.

PMID- 25859706
TI  - Alan John Flisher16 April 1957-18 April 2010Editor-in-Chief, Journal of Child and
      Adolescent Mental Health, 1999-2010.

PMID- 25859707
TI  - Letter of condolence.

PMID- 25859708
TI  - The development and course of childhood psychiatric disorders.

PMID- 25859709
TI  - Vibrational Sum Frequency Spectroscopy on Polyelectrolyte Multilayers: Effect of
      Molecular Surface Structure on Macroscopic Wetting Properties.
AB  - Adsorption of a single layer of molecules on a surface, or even a reorientation
      of already present molecules, can significantly affect the surface properties of
      a material. In this study, vibrational sum frequency spectroscopy (VSFS) has been
      used to study the change in molecular structure at the solid-air interface
      following thermal curing of polyelectrolyte multilayers of poly(allylamine
      hydrochloride) and poly(acrylic acid). Significant changes in the VSF spectra
      were observed after curing. These changes were accompanied by a distinct increase
      in the static water contact angle, showing how the properties of the layer-by
      layer molecular structure are controlled not just by the polyelectrolyte in the
      outermost layer but ultimately by the orientation of the chemical constituents in
      the outermost layers. 

PMID- 25859711
TI  - Skill and art in an intolerant world: a brief commentary on the article by Paiva
      et al.

PMID- 25859710
TI  - Controlled, Parametric, Individualized, 2-D and 3-D Imaging Measurements of
      Aerosol Deposition in the Respiratory Tract of Asthmatic Human Subjects for Model
      Validation.
AB  - BACKGROUND: Computer modeling is used to predict inhaled aerosol deposition in
      the lung based on definition of the aerosol characteristics and the breathing
      pattern and airway anatomy of the subject. Validation of the models is limited by
      the lack of detailed experimental data. Three-dimensional imaging provides an
      opportunity to address this unmet need. METHODS: Radioactive aerosol was
      administered to six male asthmatic subjects on two occasions under carefully
      monitored input conditions. Input parameters varied in particle size, depth of
      breathing, and carrier gas. The aerosol distribution was measured by combined
      single photon emission computed tomography and x-ray computer tomography
      (SPECT/CT) and airway anatomy by high resolution CT. The deposition distribution
      was measured by both a 2D and 3D analysis and described in terms of the
      percentage of inhaled aerosol deposited in sections of the respiratory tract and
      in both spatial and anatomical subdivisions within each lung. The percentage
      deposition in the conducting airways was also assessed by 24 h clearance.
      RESULTS: A set of imaging data of aerosol deposition has thus been produced in
      which the input parameters of inhalation are well described. The results in
      asthmatics were compared to previous measurements in healthy controls using an
      identical inhalation protocol. The percentages of deposition in extra-thoracic
      and thoracic compartments of the airways were not significantly affected by
      disease, but the regional pulmonary deposition pattern was, with asthma leading
      to increased deposition in the conducting airways. CONCLUSIONS: The dataset
      acquired in this study will be useful in validating computer models of aerosol
      deposition in asthmatic subjects. Asthma did not affect the fraction of inhaled
      aerosol depositing in the lungs, but gave rise to a more central deposition
      pattern. The use of 3D SPECT imaging in combination with 24 h clearance
      measurements enables differentiation of deposition between bronchial and
      bronchiolar airways.

PMID- 25859712
TI  - The crisis in water supply: how different it can look through the lens of the
      human right to water?

PMID- 25859713
TI  - Studies published in indexed journals on lawsuits for medicines in Brazil: a
      systematic review.
AB  - The aim of this systematic review was to identify and characterize articles in
      indexed scientific journals with quantitative data surveys on administrative or
      legal proceedings for access to medicines. The SciELO, LILACS, MEDLINE via
      PubMed, Embase, and Scopus databases were used. We identified 45 articles, of
      which 17 were selected. The larger studies, each covering between 2,000 and 2,927
      lawsuits, were done in the states of Sao Paulo, Rio de Janeiro, and Santa
      Catarina, Brazil. Eleven studies specified the type of legal representation, of
      which six examined cases with public attorneys and five with private attorneys.
      Only two studies reported whether the lawsuit was individual or class action, and
      in both the claims were individual. Since the majority of the medicines requested
      in the lawsuits were medium to high-cost, the review indicates that lawsuits
      contributed to the incorporation of these drugs into current pharmaceutical care
      in Brazil. 

PMID- 25859714
TI  - Cyberbullying and adolescent mental health: systematic review.
AB  - Cyberbullying is a new form of violence that is expressed through electronic
      media and has given rise to concern for parents, educators and researchers. In
      this paper, an association between cyberbullying and adolescent mental health
      will be assessed through a systematic review of two databases: PubMed and Virtual
      Health Library (BVS). The prevalence of cyberbullying ranged from 6.5% to 35.4%.
      Previous or current experiences of traditional bullying were associated with
      victims and perpetrators of cyberbullying. Daily use of three or more hours of
      Internet, web camera, text messages, posting personal information and harassing
      others online were associated with cyberbullying. Cybervictims and cyberbullies
      had more emotional and psychosomatic problems, social difficulties and did not
      feel safe and cared for in school. Cyberbullying was associated with moderate to
      severe depressive symptoms, substance use, ideation and suicide attempts. Health
      professionals should be aware of the violent nature of interactions occurring in
      the virtual environment and its harm to the mental health of adolescents. 

PMID- 25859716
TI  - Obtaining adjusted prevalence ratios from logistic regression models in cross
      sectional studies.
AB  - In the last decades, the use of the epidemiological prevalence ratio (PR) instead
      of the odds ratio has been debated as a measure of association in cross-sectional
      studies. This article addresses the main difficulties in the use of statistical
      models for the calculation of PR: convergence problems, availability of tools and
      inappropriate assumptions. We implement the direct approach to estimate the PR
      from binary regression models based on two methods proposed by Wilcosky &
      Chambless and compare with different methods. We used three examples and compared
      the crude and adjusted estimate of PR, with the estimates obtained by use of log
      binomial, Poisson regression and the prevalence odds ratio (POR). PRs obtained
      from the direct approach resulted in values close enough to those obtained by log
      binomial and Poisson, while the POR overestimated the PR. The model implemented
      here showed the following advantages: no numerical instability; assumes adequate
      probability distribution and, is available through the R statistical package. 

PMID- 25859715
TI  - The current state of play of research on the social, political and legal
      dimensions of HIV.
AB  - This paper offers a critical overview of social science research presented at the
      2014 International AIDS Conference in Melbourne, Australia. In an era of major
      biomedical advance, the political nature of HIV remains of fundamental
      importance. No new development can be rolled out successfully without taking into
      account its social and political context, and consequences. Four main themes ran
      throughout the conference track on social and political research, law, policy and
      human rights: first, the importance of work with socially vulnerable groups, now
      increasingly referred to as "key populations"; second, continued recognition that
      actions and programs need to be tailored locally and contextually; third, the
      need for an urgent response to a rapidly growing epidemic of HIV among young
      people; and fourth, the negative effects of the growing criminalization of
      minority sexualities and people living with HIV. Lack of stress on human rights
      and community participation is resulting in poorer policy globally. A new
      research agenda is needed to respond to these challenges. 

PMID- 25859717
TI  - Economic evaluation in the context of rare diseases: is it possible?
AB  - This study analyzes the available evidence on the adequacy of economic evaluation
      for decision-making on the incorporation or exclusion of technologies for rare
      diseases. The authors conducted a structured literature review in MEDLINE via
      PubMed, CRD, LILACS, SciELO, and Google Scholar (gray literature). Economic
      evaluation studies had their origins in Welfare Economics, in which individuals
      maximize their utilities based on allocative efficiency. There is no widely
      accepted criterion in the literature to weigh the expected utilities, in the
      sense of assigning more weight to individuals with greater health needs. Thus,
      economic evaluation studies do not usually weigh utilities asymmetrically (that
      is, everyone is treated equally, which in Brazil is also a Constitutional
      principle). Healthcare systems have ratified the use of economic evaluation as
      the main tool to assist decision-making. However, this approach does not rule out
      the use of other methodologies to complement cost-effectiveness studies, such as
      Person Trade-Off and Rule of Rescue. 

PMID- 25859718
TI  - Psychometric properties of the Brazilian version of the Vulnerable Elders Survey
      13 (VES-13).
AB  - This study aims to assess the psychometric properties of the Brazilian version of
      the Vulnerable Elders Survey-13 (VES-13). Interviews were carried out with
      individuals aged 60 years and over receiving care at an ambulatory cancer centre.
      Test-retest reliability was assessed using the Spearman correlation coefficient,
      intraclass correlation coefficients and Cohen's kappa coefficient. Construct
      validity was assessed by testing convergent and discriminant validity using
      principal component analysis and Varimax rotation. The Spearman correlation
      coefficient value of the comparison between test and retest scores was 0.98 (p <
      0.001). All intraclass correlation coefficient values were higher than 0.60 and
      kappa coefficients varied between 0.33 and 0.94. Three identified factors
      explained 72.6% of overall sample variance. VES-13 presented good convergent
      validity and reasonable discriminant validity. The psychometric properties of the
      adapted version of the VES-13 are consistent and adequate for use with the
      Brazilian population. 

PMID- 25859719
TI  - Territorial analysis of Aedes aegypti distribution in two Colombian cities: a
      chorematic and ecosystem approach.
AB  - A territorial analysis of Aedes aegypti density was conducted in two Colombian
      cities using an ecosystem and chorematic approach. Entomological and behavioral
      data (by cluster) and information on the urban context were used to analyze the
      relationship between territorial structures and dynamics and vector density. The
      results were represented in graphic (chorematic) models. Arauca showed higher
      vector density than Armenia. Higher density was related to unplanned
      urbanization, flood-prone areas, low socioeconomic strata, household water tanks,
      higher temperature, and recall of control measures for adult mosquitos. Zones
      with low density indices coincided with diverse socioeconomic, ecological, and
      behavioral conditions. The study found a relationship between territorial
      structures and dynamics and vector density in both Arauca and Armenia, where the
      interaction between ecological and social systems shape areas with high and low
      A. aegypti density. 

PMID- 25859720
TI  - [Vitamin A and D status among child participants in a food supplementation
      program].
AB  - Vitamin A and D serum concentrations and risk factors for their deficiencies were
      investigated in children participating in a government-sponsored fortified milk
      program. The study used multivariate linear regression analysis with hierarchical
      selection of independent variables: socio-demographic conditions, children's
      health, food consumption, breastfeeding, fortified milk, exposure to sunlight,
      anthropometric measurements, and serum concentration of retinol and 25(OH)D.
      Vitamin A and vitamin D insufficiency and deficiency values were defined as <
      1.05 umol/L, < 0.7 umol/L, < 30 ng/mL, and < 20 ng/mL, respectively. Vitamin A
      and D intake was inadequate. Prevalence rates for vitamin A and vitamin D
      insufficiency and deficiency were 19%, 6%, 82%, and 58%, respectively. Factors
      associated with low serum vitamin A were exclusive breastfeeding for less than
      120 days, low maternal schooling, maternal unemployment, more consumers of
      fortified milk in the family, and low serum vitamin D. Factors associated with
      vitamin D deficiency were low exposure to sunlight and low serum vitamin A.
      Nutritional education is needed to improve children's nutritional status.

PMID- 25859721
TI  - [Analysis of the implementation of the Tuberculosis Control Program in Brazilian
      prisons].
AB  - Tuberculosis control measures in Brazil's prison population have been regulated
      for ten years under the National Prison Health System Plan. Brazilian states have
      different organizational models for the Tuberculosis Control Program (TCP) in
      their prison systems. This study evaluated TCP implementation in prisons in two
      Brazilian states, using a multiple case study design with a qualitative approach
      and a log-frame analysis and assessment. According to predefined criteria, two
      state cases were selected, with two analytical units for each case and one prison
      hospital in Case 2. We identified partial program implementation in the Case 1
      prisons and prison hospital and low implementation in non-hospital prison health
      services in Case 2. Lack of financial investment and resources, lack of
      integration between the courts and law enforcement system and health
      institutions, and poor access to health services in prisons were adverse factors
      for program implementation. 

PMID- 25859722
TI  - [Latent structure of depression in the elderly: a taxometric analysis].
AB  - This study aimed to investigate the latent structure of depression with a non
      clinical sample of elderly, using taxometric analysis. The latter consists of a
      family of statistical procedures conceived for testing whether a given
      psychological construct is best represented by categories or dimensions in which
      individuals vary. The sample consisted of 570 elderly with a mean age of 71.9
      years (SD = 7.45), who answered the Brazilian version of the Geriatric Depression
      Scale, a cognitive test, and demographic questions. Three taxometric procedures
      were used: Mean Above Minus Below A Cut (MAMBAC), Maximum Eigenvalue (MAXEIG),
      and Latent Mode (L-mode). Sets of simulated categorical and dimensional data,
      along with the comparison curve fit indices (CCFI), oriented the study data's
      interpretation. The results with the three techniques pointed to a better fit
      with the dimensional format as opposed to the taxonic one, that is, depression
      represented better as a syndrome in which subjects are distributed along a
      continuum rather than as a discrete diagnostic entity. 

PMID- 25859723
TI  - [Stigma and discrimination: the experiences of HIV-positive women in poor
      neighborhoods of Maputo, Mozambique].
AB  - The HIV/AIDS epidemic is a serious public health problem in Mozambique. The
      country has high prevalence rates, and the epidemic's impact is aggravated by the
      stigma affecting HIV-positive persons. This study takes a socio-anthropological
      perspective to analyze the experience of HIV-positive women in poor neighborhoods
      of Maputo and the ways they cope with stigma and discrimination. Semi-structured
      interviews were conducted with 10 HIV-positive women. The results show how gender
      inequalities increase women's vulnerability to HIV and contribute to their
      stigmatization and discrimination. In dealing with stigma, women try to keep
      their diagnosis confidential, seeking support in group meetings with others
      living with HIV. Public policies should focus on women's empowerment and the
      reduction of HIV/AIDS-related stigma. 

PMID- 25859724
TI  - [Induction of hospital indebtedness due to medicine purchases under monopoly
      conditions: the case of imatinib mesylate].
AB  - Medicine expenditures consume a large share of the health budget, so knowledge on
      the use of these funds is essential for decision-making in public health and
      improvement of pharmaceutical care. This study analyzed the indebtedness of a
      high-complexity university hospital due to increased spending on imatinib
      mesylate. The descriptive study was based on analysis of documents and records in
      the Hospital Information System (SIH) from 2002 to 2010. Starting with inclusion
      of the medicine in the budget, the study mapped strategies by the pharmaceutical
      industry and government, as well as government responses to reduce the product's
      price. The systematization and publication of information stored in files and
      electronic databases can help monitor the results of programs funded by the
      Brazilian Ministry of Health. 

PMID- 25859725
TI  - [Local government and public dental health services: an analysis of inequality in
      use].
AB  - The aim of this study was to identify factors associated with the use of primary
      and specialized public dental health services and private services. A population
      based household survey was conducted in two cities of Bahia State, Brazil. Key
      informants provided data on socioeconomic variables and use of dental health
      services. Organization of the local public dental health service was ranked as
      worse versus better. Univariate and multivariate polytomous logistic regression
      was performed. Of the total of 1,290 individuals, 38.76% used private services,
      33.80% used public primary care, and 17.29% used both primary care and the Center
      for Dental Specialties. Less use of both primary care and specialized public
      services was associated with lower education (OR = 1.47; 95%CI: 1.03-2.10) and
      worse organization of services (OR = 1.74; 95%CI: 1.22-2.48), when compared to
      the exclusive use of primary care. The study showed inequality in the use of
      dental services, even when comparing more homogeneous groups, namely users of
      public services. 

PMID- 25859726
TI  - [Psychosocial and socioeconomic factors related to insomnia and menopause: Pro
      Saude Study].
AB  - This study evaluated the association between insomnia and menopausal status and
      the influence of socioeconomic and psychosocial variables on this association in
      a cross-sectional analysis of 2,190 university employees (the Pro-Saude Study). A
      self-administered questionnaire was used, covering menopausal status, complaints
      of insomnia, common mental disorders, stressful life events, social support, and
      socioeconomic variables. Odds ratios were calculated using logistic regression
      with a polytomous outcome. After adjusting for potential socio-demographic
      confounders, women who had entered menopause more than 60 months previously were
      more likely to report complaints with sleep (OR 1.53-1.86) as compared to women
      in menopause for less than 60 months. After adjusting for psychosocial variables,
      in the first group the ORs decreased to 1.53 (95%CI: 0.92-2.52) for difficulty
      initiating sleep, 1.81 (95%CI: 1.09-2.98) for difficulty maintaining sleep, and
      1.71 (95%CI: 1.08-2.73) for general complaints of insomnia. Psychosocial factors
      can mediate the manifestation of insomnia among menopausal women. 

PMID- 25859727
TI  - [Motherhood behind bars: the struggle for citizens' rights and health for women
      inmates and their children in Brazil].
AB  - This study analyzes the links between health, rights, legislation, and public
      policies based on document research on legal safeguards for women and their
      children residing in prison. The research was conducted at the Federal level and
      in four States of Brazil: Rio Grande do Sul, Mato Grosso, Parana, and Sao Paulo.
      The study aims to back measures by public agencies to guarantee such rights and
      to raise awareness of the problem, given the extreme vulnerability of women
      inmates and their children and the issue's legal and administrative invisibility.
      The authors identified 33 different legal provisions as points of tension, such
      as the possibility of house arrest and disparities in the terms and conditions
      for children to remain inside the prison system. Various provisions cite the
      Constitutional guarantee of women inmates' right to breastfeed in prison.
      Meanwhile, the study found gaps in other issues pertaining to motherhood in
      prison, expressed as dual incarceration (imprisonment arbitrarily extended to
      their children). It is necessary to expand and enforce the existing legislation
      to prevent such violations of rights. 

PMID- 25859728
TI  - [Retail food outlets and the association with overweight/obesity in
      schoolchildren from Florianopolis, Santa Catarina State, Brazil].
AB  - The study analyzes retail food outlets and their association with
      overweight/obesity in schoolchildren from Florianopolis, Santa Catarina State,
      Brazil. The study used a cross-sectional design with a random sample of 2,506
      schoolchildren from public (n = 19) and private schools (n = 11). Overweight and
      obesity were classified according to World Health Organization guidelines for
      2007, and crude and adjusted analyses were performed using Poisson regression.
      Prevalence of overweight/obesity was 34.2%. In public schools, 19.6% of the
      children were overweight and 13.5% were obese, as compared to 22.4% and 11.1% in
      private schools. An association was found in the public school system between
      overweight/obesity and the use of bakeries for food purchases (p = 0.004). In the
      private school system, children of families that bought groceries at the
      supermarket showed 26% less overweight/obesity compared to those who did not (p =
      0.003). The data show an association between some types of food outlets
      (supermarkets and bakeries) and prevalence of overweight/obesity in the school
      age population. 

PMID- 25859729
TI  - Pesticide exposure and health conditions of terrestrial pesticide applicators in
      Cordoba Province, Argentina.
AB  - Agricultural workers represent a population that is highly vulnerable to the
      toxic effects of pesticide exposure. This cross sectional study aimed to describe
      the health conditions of terrestrial pesticide applicators in Cordoba Province,
      Argentina, their work practices and socio-demographic characteristics, by means
      of a standardized self-administered questionnaire (n = 880). A descriptive
      analysis reported a high prevalence of occasional or frequent symptoms: 47.4% had
      symptoms of irritation, 35.5% fatigue, 40.4% headache and 27.6% nervousness or
      depression. Using logistic regression models, risk and protective factors were
      found for symptoms of irritation, medical consultation and hospitalization. Among
      the occupational exposure variables, marital status, length of time in the job,
      low level of protection with regard to the use of personal protective equipment,
      combined use of different pesticides and the application of the insecticide
      endosulfan, were associated with a higher frequency of reported symptoms and
      higher consultation rates and hospitalization. 

PMID- 25859730
TI  - [The Brazilian National List of Medicines: a work in progress].

PMID- 25859731
TI  - [The authors reply].

PMID- 25859733
TI  - HIV/AIDS and mental health research in sub-Saharan Africa: a systematic review.
AB  - The relationship between mental illness and HIV/AIDS is complex and
      bidirectional. A significant amount of research has been performed in high-income
      countries but less is known about HIV and mental health in sub-Saharan Africa.
      The objectives of the review were to search the literature for quantitative
      studies conducted in sub-Saharan Africa on mental health and HIV and to
      critically evaluate and collate the studies in order to identify research needs
      and priorities. The databases Ovid, MEDLINE, PsycINFO and the Social Sciences
      Citation Index (SSCI) were searched for variations of search terms related to
      HIV/AIDS and mental health and studies limited to the populations of African
      countries. In addition, we hand-searched indexes of key journals and the
      databases of academic theses. We included 104 papers or research publications.
      The majority of these were published after 2005. The major topics covered were:
      mental-health-related HIV-risk behaviour, HIV in psychiatric populations, and
      mental illness in HIV-positive populations. The reported prevalence levels of
      mental illness among people living with HIV or AIDS (PLHIV) was high, with all
      but one study noting a prevalence of 19% or higher. Neurocognitive changes in
      adults with HIV were also prevalent, with reported deficits of up to 99% in
      symptomatic PLHIV and 33% in non-symptomatic PLHIV. Research on HIV in relation
      to mental health is increasing; however, there is a need for good-quality
      prospective studies to investigate the bidirectional effects of mental illness
      and HIV on each other. 

PMID- 25859732
TI  - Suramin, Genistein and Collagen Matrix (DuraGen) for Delayed Adjustment after
      Strabismus Surgery: Which One is Best?
AB  - AIM: To evaluate the efficacy and safety of suramin, genistein and collagen
      matrix for the prevention of inflammation, the reduction of fibrosis and the
      delay in adjustment after strabismus surgery on a rabbit model. METHODS: By using
      an adjustable suture technique, a recession of the superior rectus muscle (SRM)
      was made in 36 eyes of 18 rabbits. Three study groups were created using
      genistein, suramin and collagen matrix (n = 6 per group). Two control groups
      utilized dimethyl sulphoxide (DMSO) (n = 6) and balanced salt solution (n = 12).
      The adjustments and measurements were made on days 2, 7, 14. After enucleation
      was done on day 21, the degree of inflammation was evaluated quantitatively in
      histopathological sections and immunohistochemical investigations were performed
      for tissue expression of cytoplasmic vascular endothelial growth factor (VEGF),
      MAC 387, TGF-beta and bFGF. RESULTS: The adhesions between conjunctiva and SRM
      were significantly less in the collagen matrix and suramin groups (p = 0.002) and
      adhesions between the sclera and SRM were considerably reduced in the genistein
      and DMSO groups (p = 0.006) on day 7. Force exerted for adjustment was
      significantly less in the collagen matrix and suramin groups on day 14 (p =
      0.006). Expression of b-FGF was significantly lower in the conjunctival
      epithelium in the suramin and genistein groups (p = 0.0001 for both). TGF-beta
      was significantly lower (p = 0.001) in the suramin group and VEGF expression was
      totally absent. MAC 387 expression was lower in the genistein and suramin groups
      (p = 0.0001). CONCLUSION: Suramin, genistein and collagen matrix successfully
      reduce adhesions, and facilitate adjustment following recession surgery. Both
      suramin and genistein effectively suppress growth factor expression, while
      collagen matrix offers the longest time interval for adjustability after
      strabismus surgery.

PMID- 25859734
TI  - Correlates of sexual faithfulness among low-literate rural males in the Amhara
      Region of Ethiopia.
AB  - HIV is a major threat to the people of the rural Amhara Region, northwest
      Ethiopia. To date, numerous studies have focused on condom use for HIV
      prevention. Using the theory of planned behaviour, this study investigates the
      psychosocial determinants of intended sexual faithfulness among rural males in
      the Amhara Region. In February 2008, we conducted a cross-sectional study with
      100 males, with an age range of 20-50 years (mean age 38 years), in Dejen Woreda.
      The participants were illiterate or had a low level of literacy and all were
      rural farmers. Consequently, 10 literate male data collectors were recruited from
      the same community to assist in collecting data by means of a structured
      questionnaire. In the analysis of social cognitions as determinants of sexual
      faithfulness, attitude to faithfulness emerged as the best predictor of intended
      faithfulness, with significant contributions from self-efficacy and social norm
      for faithfulness. Thus, balanced and comprehensive HIV interventions focusing on
      attitudes, self-efficacy and social norms pertaining to faithfulness, sexual
      abstinence and condom use are needed to halt the spread of HIV among low-literate
      males in rural Amhara. 

PMID- 25859735
TI  - Negotiating therapeutic citizenship and notions of masculinity in a South African
      village.
AB  - The article explores the idea of therapeutic citizenship in relation to the
      experiences of men who attend support groups for people living with HIV or AIDS
      (PLHIV). At a rural South African health facility offering free antiretroviral
      (ARV) medicines, support groups aim to empower HIV-positive clients through
      knowledge and skills that enable them to adhere to their ARV regimen. Members are
      exhorted to abandon their 'traditional' health and gender beliefs in favour of a
      biomedical understanding and approach to health; to embrace participation in a
      support group for PLHIV; and to actively challenge HIV stigma through the public
      disclosure of their HIV-test result. Fourteen months of ethnographic fieldwork
      conducted in Bushbuckridge, Mpumalanga Province, South Africa, investigated how
      men negotiated these efforts - normally characterised in the academic literature
      as 'therapeutic citizenship' - in relation to men's socio-cultural definitions of
      masculinity. The findings reveal that most of the men gained the knowledge and
      skills necessary to adhere to treatment. Although they generally behaved in a
      disciplined way, they remained doubtful about their commitment to the particular
      kind of 'HIV identity' that a support group conferred on them. Men who embrace
      this identity must abandon their previous masculine lifestyles and conform to the
      support group's messages concerning what it means to be a 'responsible' HIV
      patient. The research documents some of the challenges men experience in
      negotiating these conflicting demands. The discussion draws on personal accounts
      by the participants to illustrate the ambivalence of men towards their 'HIV
      identity' and to belonging to a support group. 

PMID- 25859736
TI  - Understanding HIV-related posttraumatic stress disorder in South Africa: a review
      and conceptual framework.
AB  - A number of epidemiological studies have attempted to measure the prevalence of
      HIV-related posttraumatic stress disorder (PTSD) in sub-Saharan Africa. A
      systematic review of the literature identified eight relevant studies that put
      current estimates of the prevalence of HIV-related PTSD between 4.2% and 40%.
      Even the lower estimates suggest that PTSD in response to the trauma of being
      diagnosed and living with HIV is a significant mental health burden. However, a
      conceptual framework to advance our understanding of the prevalence and
      phenomenology of HIV-related PTSD is lacking. This article argues that the Ehlers
      & Clark (2000) cognitive model of PTSD provides a useful conceptual framework for
      understanding HIV-related PTSD in South Africa. The model emphasises the role of
      trauma appraisals in the development and maintenance of PTSD, which can also be
      usefully applied to some of the other psychological disorders associated with HIV
      infection. The model appears to fit some of the important research findings, and
      it offers insights into the relationships between HIV-related PTSD and other
      psychological disorders, HIV stigma, the high prevalence of non-HIV traumatic
      events, occasional problems with the delivery of antiretroviral drugs in the
      South African public health service, the unpredictable course of HIV illness, and
      the quality of HIV testing and counselling. Implications for individual treatment
      strategies and broader public health interventions are briefly discussed. 

PMID- 25859737
TI  - Socioeconomic status and barriers to the use of free antiretroviral treatment for
      HIV/AIDS in Enugu State, south-eastern Nigeria.
AB  - With about 3 million people living with HIV, Nigeria has approximately 8% of the
      global burden of HIV cases. In 2009, only about 34% of those in need of
      antiretroviral treatment (ART) were able to access care, which means that Nigeria
      was far from achieving the United Nations target of 'universal access' by 2010.
      This study aimed to describe the barriers to accessibility and the coping
      strategies employed to overcome these barriers among users of free ART services
      overall and by socioeconomic status (SES). Data were collected from 240 people
      receiving ART at one urban and one peri-urban health facility in Enugu State,
      south-eastern Nigeria. Information on SES, demographic characteristics, and
      barriers and coping mechanisms for accessing ART were elicited from the
      respondents. The high cost of transportation, HIV stigma, and long waiting hours
      were found to be key barriers to the use of ART services. On average, ART clients
      spent just under four hours at the clinic during their monthly appointments. The
      use of personal savings and financial support from relatives were the main means
      to access treatment. When the data were analysed according to clients' SES,
      transportation costs were a chief concern among the poorest while those who were
      better off were more likely to be concerned about stigma and discrimination.
      These findings should be borne in mind when designing and locating services to
      maximise ongoing accessibility to ART. 

PMID- 25859738
TI  - 'Keeping healthy in the backseat': How motherhood interrupted HIV treatment in
      recently delivered women in Kenya.
AB  - Although there is a large body of literature related to the experiences of
      motherhood and aspects of the change that it brings about, how the experience of
      motherhood affects the healthcare of women with chronic illness is less
      documented. This study explores how motherhood in newly delivered HIV-infected
      mothers in Kenya interrupted their antiretroviral treatment (ART). Qualitative
      interviews were performed with 26 mothers on ART in a rural or urban area. The
      data were organised and interpreted using content analysis. The study found that
      adherence to ART was influenced by contextual differences in socio-cultural
      expectations and family relationships. Urban life enabled women to make decisions
      on their own and to negotiate challenges that were often unpredictable. Women in
      rural areas knew what was expected of them and decisions were normally not for
      them to make alone. The women in Busia and Kibera had difficulties combining
      adherence with attaining the socio-cultural definition of good mothering. Lack of
      support from health providers and weak healthcare systems contributed to
      inadequate stocks of HIV drugs and inaccessibility of HIV-related care. From the
      data, we developed the main theme 'keeping healthy in the backseat' and the two
      sub-themes 'regaining self-worth through motherhood' and 'mother first - patient
      later.' We suggest that motherhood is context-specific and follows socio-cultural
      practises, which made it difficult for the women in Kenya to follow ART
      instructions. There is a need to reassess HIV-related services for mothers on ART
      in order to give them a better chance to stay on treatment and satisfy their
      aspiration to be 'good mothers.' Context-specific HIV-treatment policies are
      necessary for ensuring adherence and successful treatment outcomes. 

PMID- 25859739
TI  - The role of 'pimping' in the mediation of transactional sex at a university
      campus in Zimbabwe.
AB  - The article focuses on a very specific form of transactional sex that exists at a
      university campus in Zimbabwe, which students refer to as 'pimping.' Drawing
      extensively on the specific experiences of a male student pimp, the article
      demonstrates that, in practice, transactional sex takes different forms and is
      not always confined to two parties (namely, a woman and a man). In this case,
      'pimp-mediated' transactional sex introduces a third person - the pimp - into
      what is traditionally understood to be a relationship between the two parties
      and, in the process, dramatically transforms the social obligations that define
      this particular social relation. A major transformation that occurs in pimp
      mediated transactional sex is that it makes the pimps, rather than the women, the
      central people in these relationships. This, I argue, makes transactional sex
      more efficient and potentially increases the female participants' vulnerability
      to HIV infection. 

PMID- 25859740
TI  - The influence of antiretroviral treatment on willingness to test: a qualitative
      study in rural KwaZulu-Natal, South Africa.
AB  - Previous quantitative studies suggest a mutually reinforcing relationship between
      HIV counselling and testing (HCT) and antiretroviral treatment (ART). HCT is the
      entry into ART, and access to ART appears to increase HIV-testing uptake in
      settings with historically low uptake. Adopting a qualitative approach, this
      study examined the influence of ART on willingness to test for HIV, in a rural
      community in South Africa. Ninety-six in-depth interviews from a large community
      based HIV-prevention trial were analysed. The data provide insight into the
      community members' views, perceptions and experiences regarding ART, and how they
      draw on these in making decisions about HIV testing. Several key factors that
      supported a positive relationship between ART and HIV testing were noted. These
      included the beliefs that ART brings hope and that it prolongs life; the powerful
      positive effect of witnessing the recovery of someone on treatment; and that ART
      encourages early HIV-testing behaviour. A few negative factors that could
      potentially weaken the effects of this positive relationship between ART and HCT
      uptake were the disclosure difficulties experienced by those enrolled in
      treatment, beliefs that ART does not cure HIV disease, and the travel distance to
      testing and treatment facilities from where people live and work. HIV/AIDS
      service providers and programme planners should actively draw on these
      observations, to encourage increased HIV testing in communities and to ensure
      that the maximum number of people get the HIV treatment and care services that
      they require. 

PMID- 25859741
TI  - Protein-glycolipid interactions studied in vitro using ESI-MS and nanodiscs:
      insights into the mechanisms and energetics of binding.
AB  - Electrospray ionization-mass spectrometry (ESI-MS) analysis combined with the use
      of nanodiscs (NDs) to solubilize glycolipids (GLs) has recently emerged as a
      promising analytical method for detecting protein-GL interactions in vitro and,
      when applied to libraries of GLs, ranking their affinities. However, there is
      uncertainty regarding the mechanism(s) of complex formation in solution and the
      extent to which the relative abundances of protein-glycolipid complexes observed
      by ESI-MS reflect the relative concentrations in solution. Here, we describe the
      results of a systematic ESI-MS study aimed at elucidating the processes that
      influence binding of water-soluble proteins to GLs incorporated into NDs and to
      exploit these insights to quantify the binding energetics. The interactions
      between the cholera toxin B subunit homopentamer (CTB5) and its native
      ganglioside receptor, beta-D-Gal-(1 -> 3)-beta-D-GalNAc-(1 -> 4)-[alpha-D-Neu5Ac
      (2 -> 3)]-beta-D-Gal-(1 -> 4)-beta-D-Glc-ceramide (GM1), and between a
      recombinant fragment of family 51 carbohydrate-binding module (CBM), originating
      from S. pneumoniae, with a synthetic B type 2 neoglycolipid, alpha-D-Gal-(1 -> 3)
      [alpha-L-Fuc-(1 -> 2)]-beta-D-Gal-(1 -> 4)-beta-D-GlcNAc-1,2-di-O-dodecyl-sn
      glycero (B2NGL) served as model protein-GL complexes for this study. The results
      of the ESI-MS measurements reveal that proteins bind reversibly to ND-bound GLs
      and that proteins possessing multiple ligand binding sites are able to interact
      with GLs originating from different NDs. Experimental evidence suggests that the
      diffusion of GLs between NDs is rapid and influences the nature of the protein-GL
      complexes that are detected. Using a newly developed ESI-MS assay, the proxy
      ligand method, the association constants for the CBM-B2NGL and CTB5-GM1
      interactions were quantified and found to be slightly smaller than those for the
      corresponding oligosaccharides in solution. 

PMID- 25859742
TI  - Multifunctional radical-doped polyoxometalate-based host-guest material:
      photochromism and photocatalytic activity.
AB  - An effective strategy to synthesize multifunctional materials is the
      incorporation of functional organic moieties and metal oxide clusters via self
      assembly. A rare multifunctional radical-doped zinc-based host-guest crystalline
      material was synthesized with a fast-responsive reversible ultraviolet visible
      light photochromism, photocontrolled tunable luminescence, and highly selective
      photocatalytic oxidation of benzylic alcohols as a result of blending of
      distinctively different functional components, naphthalenediimide tectons, and
      polyoxometalates (POMs). It is highly unique to link pi-electron-deficient
      organic tectons and POMs by unusual POMs anion-pi interactions, which are not
      only conducive to keeping the independence of each component but also effectively
      promoting the charge transfer or exchange among the components to realize the
      fast-responsive photochromism, photocontrolled tunable luminescence, and
      photocatalytic activity. 

PMID- 25859743
TI  - Super-narrow, extremely high quality collective plasmon resonances at telecom
      wavelengths and their application in a hybrid graphene-plasmonic modulator.
AB  - We present extremely narrow collective plasmon resonances observed in gold
      nanostripe arrays fabricated on a thin gold film, with the spectral line full
      width at half-maximum (fwhm) as low as 5 nm and quality factors Q reaching 300,
      at important fiber-optic telecommunication wavelengths around 1.5 MUm. Using
      these resonances, we demonstrate a hybrid graphene-plasmonic modulator with the
      modulation depth of 20% in reflection operated by gating of a single layer
      graphene, the largest measured so far. 

PMID- 25859744
TI  - A qualitative analysis of health professionals' job descriptions for surgical
      service delivery in Uganda.
AB  - BACKGROUND: The ever increasing demand for surgical services in sub-Saharan
      Africa is creating a need to increase the number of health workers able to
      provide surgical care. This calls for the optimisation of all available human
      resources to provide universal access to essential and emergency surgical
      services. One way of optimising already scarce human resources for health is by
      clarifying job descriptions to guide the scope of practice, measuring
      rewards/benefits for the health workers providing surgical care, and informing
      education and training for health professionals. This study set out to determine
      the scope of the mandate to perform surgical procedures in current job
      descriptions of surgical care health professionals in Uganda. METHODS: A document
      review was conducted of job descriptions for the health professionals responsible
      for surgical service delivery in the Ugandan Health care system. The job
      descriptions were extracted and subjected to a qualitative content data analysis
      approach using a text based RQDA package of the open source R statistical
      computing software. RESULTS: It was observed that there was no explicit mention
      of assignment of delivery of surgical services to a particular cadre. Instead the
      bulk of direct patient related care, including surgical attention, was assigned
      to the lower cadres, in particular the medical officer. Senior cadres were
      assigned to perform predominantly advisory and managerial roles in the health
      care system. In addition, a no cost opportunity to task shift surgical service
      delivery to the senior clinical officers was identified. CONCLUSIONS: There is a
      need to specifically assign the mandate to provide surgical care tasks, according
      to degree of complexity, to adequately trained cadres of health workers. Health
      professionals' current job descriptions are not explicit, and therefore do not
      adequately support proper training, deployment, defined scope of practice, and
      remuneration for equitable surgical service delivery in Uganda. Such deliberate
      assignment of mandates will provide a means of increasing surgical service
      delivery through further optimisation of the available human resources for
      health.

PMID- 25859745
TI  - Exploiting topic modeling to boost metagenomic reads binning.
AB  - BACKGROUND: With the rapid development of high-throughput technologies,
      researchers can sequence the whole metagenome of a microbial community sampled
      directly from the environment. The assignment of these metagenomic reads into
      different species or taxonomical classes is a vital step for metagenomic
      analysis, which is referred to as binning of metagenomic data. RESULTS: In this
      paper, we propose a new method TM-MCluster for binning metagenomic reads. First,
      we represent each metagenomic read as a set of "k-mers" with their frequencies
      occurring in the read. Then, we employ a probabilistic topic model -- the Latent
      Dirichlet Allocation (LDA) model to the reads, which generates a number of hidden
      "topics" such that each read can be represented by a distribution vector of the
      generated topics. Finally, as in the MCluster method, we apply SKWIC -- a variant
      of the classical K-means algorithm with automatic feature weighting mechanism to
      cluster these reads represented by topic distributions. CONCLUSIONS: Experiments
      show that the new method TM-MCluster outperforms major existing methods,
      including AbundanceBin, MetaCluster 3.0/5.0 and MCluster. This result indicates
      that the exploitation of topic modeling can effectively improve the binning
      performance of metagenomic reads.

PMID- 25859746
TI  - CE: Atrial Fibrillation: Updated Management Guidelines and Nursing Implications.
AB  - OVERVIEW: Atrial fibrillation, the most common chronic cardiac arrhythmia,
      adversely affects the quality of life of millions of people. The condition is
      frequently associated with advancing age, structural cardiac dysfunction, and
      preexisting comorbidities. The most common complications, stroke and heart
      failure, result in significant morbidity and mortality. Indeed, atrial
      fibrillation is responsible for over 450,000 hospitalizations and 99,000 deaths
      annually and adds up to $26 billion to U.S. health care costs each year. Given
      the aging of the U.S. population, the incidence of atrial fibrillation is
      expected to double within the next 50 years. There is evidence that nursing
      intervention in patient education and transition of care coordination can improve
      adherence to treatment plans and patient outcomes.This article reviews the
      recently updated guideline for the management of atrial fibrillation, issued
      jointly by the American Heart Association, the American College of Cardiology,
      and the Heart Rhythm Society. It focuses on the prevention of thromboembolism and
      on symptom control, and stresses the importance of patient adherence to treatment
      plans in order to ensure better outcomes.

PMID- 25859747
TI  - CE: Epilepsy Update, Part 1: Refining Our Understanding of a Complex Disease.
AB  - OVERVIEW: Epilepsy is a serious, common neurologic disease that affects people of
      all ages. As underscored in the 2012 Institute of Medicine report Epilepsy Across
      the Spectrum: Promoting Health and Understanding, the millions of people living
      with epilepsy in the United States face the challenges of seeking out high
      quality, coordinated health care and community services; overcoming epilepsy
      misinformation and stigma; and finding understanding and support in their
      communities. This article, the first in a two-part series, discusses new research
      that has increased our understanding of epilepsy's etiology and pathophysiology,
      new definitions that are changing the ways we evaluate and treat this disease,
      conditions that frequently present with epilepsy, and psychosocial challenges
      faced by people with epilepsy. Part 2, which will appear in next month's issue,
      reviews comprehensive nursing care and evidence-based treatment for epilepsy and
      presents resources for people with epilepsy and their families.

PMID- 25859748
TI  - Patient perspectives of barriers and facilitators of treatment-seeking behaviors
      for stroke care.
AB  - OBJECTIVE: Delays in seeking treatment for stroke care are associated with
      greater disability and reductions in stroke outcomes. The objective of this study
      was to qualitatively examine facilitators and barriers to urgently seeking stroke
      related care. METHODS: A qualitative analytic approach was used to explore
      facilitators and barriers to seeking stroke care in an urgent manner. Sixty-four
      stroke survivors offered information related to facilitators and barriers to
      stroke care via a structured survey as part of a larger mixed-methods study
      designed to measure stroke outcomes. RESULTS: Three themes emerged related to
      facilitators and barriers: (a) recognition of symptoms, (b) social support, and
      (c) knowledge and ability to call emergency medical services as a first response.
      Facilitators to urgent care-seeking behaviors included classic stroke symptoms,
      severe symptoms, sudden symptom onset, and high perceived level of emergency.
      Social support and knowledge/ability to call emergency medical services also
      emerged as facilitators of urgent care. Barriers to urgent care-seeking behaviors
      included atypical symptoms, mild symptoms, gradual symptom onset, and low
      perceived level of emergency. CONCLUSIONS: Individuals who experience strokes
      face a number of facilitators and barriers to seeking urgent care for their
      condition. Facilitators and barriers are associated with stroke symptoms and
      their personal environments. Additional study of barriers to stroke care is
      needed to adequately design interventions to reduce delays in seeking treatment.

PMID- 25859749
TI  - Secondary health conditions in individuals with multiple sclerosis: a cross
      sectional web-based survey analysis.
AB  - PURPOSE: The purpose of this study was to compare the rates of secondary health
      conditions in individuals with multiple sclerosis (MS) with age-matched U.S.
      general population norms. METHOD: This was a cross-sectional study in which data
      were collected using a Web-based survey from members of the greater Midwest MS
      society chapter. Questions were modeled from the National Health Interview Survey
      to assess the presence of six health conditions. Self-reported health conditions
      among the sample were compared to U.S. general population norms from the National
      Health Interview Survey. RESULTS: Individuals with MS reported higher rates of
      depression, arthritis, diabetes, coronary artery disease, migraine headaches, and
      cancer than the normative population. Although the rates of health conditions
      increased with age in the normative sample, the MS sample showed a curvilinear
      (bimodal) pattern as a function of age for some secondary health conditions.

PMID- 25859750
TI  - Arrhythmias in the epilepsy monitoring unit: watching for sudden unexpected death
      in epilepsy.
AB  - Nurses who work with patients at risk for seizures should be informed that both
      adult and pediatric patients are at risk for sudden unexpected death in epilepsy
      (SUDEP). Although the exact pathophysiology of SUDEP is not determined, patients
      with mesial temporal lobe epilepsy represent an at-risk population because of
      autonomic dysregulation. With prompt treatment, patients with near-SUDEP can
      continue to lead normal productive lives. This case series presents three
      patients with near-SUDEP diagnosed with temporal lobe epilepsy. 

PMID- 25859751
TI  - Bilateral locked anterior shoulder dislocation in a bench-pressing athlete: case
      report.
AB  - Chronic bilateral anterior shoulder dislocation is a rare entity. Treatment
      options range from conservative to surgical reduction. We present a case of a
      young bench-pressing athlete with bilateral locked anterior shoulder dislocation
      without fracture. Upon presentation, the patient had no pain with functional
      range of motion so he refused surgery. Conservative treatment could be an
      acceptable alternative to surgical intervention if pain and functional status are
      satisfactory. 

PMID- 25859753
TI  - Expanding patient access to quality medication-related information: the potential
      of medication hotlines to improve patient adherence in schizophrenia.
AB  - Medication nonadherence is a widespread problem that compromises treatment
      outcomes, particularly in schizophrenia. Weersink et al. (Soc Psychiatry
      Psychiatr Epidemiol, 2015) describe telephone calls to a national medicines
      information line, with a focus on queries related to antipsychotic medications.
      Their analysis of callers' questions and concerns offers a valuable window into
      patient and caregiver perspectives. Given that many callers reported that they
      had not shared these concerns with a health care provider, this study also
      highlights the capacity of medication hotlines to address unmet needs.
      Establishing and maintaining long-term treatment regimens is a complex task, and
      truly patient-centered care requires a variety of creative and accessible support
      resources. Medication lines have the potential to serve as a resource and to
      provide proactive and timely adherence support.

PMID- 25859752
TI  - An international consensus approach to the management of atypical hemolytic
      uremic syndrome in children.
AB  - Atypical hemolytic uremic syndrome (aHUS) emerged during the last decade as a
      disease largely of complement dysregulation. This advance facilitated the
      development of novel, rational treatment options targeting terminal complement
      activation, e.g., using an anti-C5 antibody (eculizumab). We review treatment and
      patient management issues related to this therapeutic approach. We present
      consensus clinical practice recommendations generated by HUS International, an
      international expert group of clinicians and basic scientists with a focused
      interest in HUS. We aim to address the following questions of high relevance to
      daily clinical practice: Which complement investigations should be done and when?
      What is the importance of anti-factor H antibody detection? Who should be treated
      with eculizumab? Is plasma exchange therapy still needed? When should eculizumab
      therapy be initiated? How and when should complement blockade be monitored? Can
      the approved treatment schedule be modified? What approach should be taken to
      kidney and/or combined liver-kidney transplantation? How should we limit the risk
      of meningococcal infection under complement blockade therapy? A pressing question
      today regards the treatment duration. We discuss the need for prospective studies
      to establish evidence-based criteria for the continuation or cessation of
      anticomplement therapy in patients with and without identified complement
      mutations. 

PMID- 25859754
TI  - The association of trends in charcoal-burning suicide with Google search and
      newspaper reporting in Taiwan: a time series analysis.
AB  - PURPOSE: Some East/Southeast Asian countries have experienced a rapid increase in
      suicide by charcoal burning over the past decade. Media reporting and Internet
      use were thought to contribute to the epidemic. We investigated the association
      between method-specific suicide incidence and both Internet search volume and
      newspaper reporting in Taiwan. METHOD: Weekly data for suicide, suicide-related
      Google search volume, and the number of articles reporting suicide in four major
      newspapers in Taiwan during 2008-2011 were obtained. Poisson autoregressive
      regression models were used to examine the associations between these variables.
      RESULTS: In the fully adjusted models, every 10 % increase in Google searches was
      associated with a 4.3 % [95 % confidence interval (CI) 1.1-7.6 %] increase in
      charcoal-burning suicide incidence in the same week, and a 3.8 % (95 % CI 0.4-7.2
      %) increase in the following week. A one-article increase in the United Daily was
      associated with a 3.6 % (95 % CI 1.5-5.8 %) increase in charcoal-burning suicide
      in the same week. By contrast, non-charcoal-burning suicide was not associated
      with Google search volume, but was associated with the Apple Daily's reporting in
      the preceding week. CONCLUSIONS: We found that increased Internet searches for
      charcoal-burning suicide appeared to be associated with a subsequent increase in
      suicide by this method. The prevention of suicide using emerging methods may
      include monitoring and regulating online information that provides details of
      these methods as well as encouraging Internet service providers to provide help
      seeking information.

PMID- 25859756
TI  - Innovative patient care practices using social media.
AB  - OBJECTIVE: To characterize the literature on social media applications used to
      deliver patient care. DATA SOURCES: A search of the literature was conducted on
      June 11, 2014, using PubMed, MEDLINE, CINAHL, and Communication Abstracts
      databases for clinical studies between 2004 and 2014. A combination of the search
      terms "social media" or "Web 2.0" or "online social networking" or "Facebook" or
      "Twitter" AND "patient care" or "health care" was used. In addition, 42
      additional abstracts were retrieved from www.patientslikeme.com for review. STUDY
      SELECTION: Only published, peer-reviewed journal articles were considered and
      only publications in English were included. The abstracts from this search were
      reviewed for relevance to Web-based social media platforms being used in patient
      care activities. DATA SYNTHESIS: A total of 35 articles were included in the
      review. A majority of the studies published on social media and patient care used
      cross-sectional designs and were conducted in the United States. Multiple social
      media applications were studied, but Facebook was the predominant social media
      tool found. Patient care opportunities for various diseases with social media
      have been studied. Recurring themes included overcoming barriers, engaging and
      empowering patients, enhancing research, providing information for health
      promotion, scratching the surface, and potential pitfalls. CONCLUSION: Social
      media have the potential to help patients and practitioners overcome multiple
      barriers in the delivery of health care. Maintaining patient privacy, security of
      information shared in the platform, and integrity of information shared are all
      concerns when using this type of Web application.

PMID- 25859755
TI  - Normalization of CEA Levels Post-Neoadjuvant Therapy is a Strong Predictor of
      Pathologic Complete Response in Rectal Cancer.
AB  - BACKGROUND: Recent attention has been focused on the relationship between
      carcinoembryonic antigen (CEA) and pathological complete response (pCR), without
      consensus regarding its predictive value. This study aims to examine the
      association between CEA and pCR. METHODS: We conducted a retrospective review of
      a prospectively maintained database of all patients who underwent primary rectal
      cancer resection after neo-adjuvant chemoradiotherapy (nCRT). Patients were
      divided into two groups, pCR or no-pCR, based on final pathology. CEA levels were
      measured at the initial visit with the surgeon/oncologist and post-completion of
      nCRT. RESULTS: One hundred and forty-one patients underwent primary rectal cancer
      resections after nCRT. Nineteen patients (13.5 %) achieved pCR, while 122 (86.5
      %) had no-pCR. Pre-nCRT CEA levels were not significantly different between
      groups (2.75 vs 4.5 MUg/L, p = 0.65). However, post-nCRT CEA levels were
      significantly lower in patients with pCR (1.7 vs 2.4 MUg/L, p < 0.01). On
      multivariate logistic regression analyses, low post-nCRT CEA level was an
      independent predictor of pCR (OR 1.74, CI 1.06, 3.81) and normalization of CEA
      from an initially elevated level was a highly significant predictor of pCR (OR
      64.8, CI 2.53, 18,371). CONCLUSION: Low post-nCRT CEA is an independent predictor
      of pCR, and normalization of CEA post-nCRT is a strong predictor of pCR.

PMID- 25859757
TI  - Patterns of attachment of the myodural bridge by the rectus capitis posterior
      minor muscle.
AB  - The myodural bridge was first described by Hack in 1995 and was thought to be
      related to chronic cervicogenic headaches. For a long time, few studies revealed
      the patterns of the myodural bridge considering the rectus capitis posterior
      minor muscle. In this study, P45 plastination technology and anatomical
      dissection were performed on head specimens, and four different terminal region
      types of the rectus capitis posterior minor muscle were observed, including the
      posterior atlanto-occipital interspace, posterior arch of the atlas and posterior
      atlanto-axial interspace. We propose that the myodural complex structures in the
      posterior atlanto-occipital and posterior atlanto-axial interspace have
      cooperative effects on cerebrospinal fluid and work together. This force might be
      an important source for the circulation of cerebrospinal fluid. 

PMID- 25859760
TI  - New in situ solid-state NMR techniques for probing the evolution of
      crystallization processes: pre-nucleation, nucleation and growth.
AB  - The application of in situ techniques for investigating crystallization processes
      promises to yield significant new insights into fundamental aspects of
      crystallization science. With this motivation, we recently developed a new in
      situ solid-state NMR technique that exploits the ability of NMR to selectively
      detect the solid phase in heterogeneous solid-liquid systems (of the type that
      exist during crystallization from solution), with the liquid phase "invisible" to
      the measurement. As a consequence, the technique allows the first solid particles
      produced during crystallization to be observed and identified, and allows the
      evolution of different solid phases (e.g., polymorphs) present during the
      crystallization process to be monitored as a function of time. This in situ solid
      state NMR strategy has been demonstrated to be a powerful approach for
      establishing the sequence of solid phases produced during crystallization and for
      the discovery of new polymorphs. The most recent advance of the in situ NMR
      methodology has been the development of a strategy (named "CLASSIC NMR") that
      allows both solid-state NMR and liquid-state NMR spectra to be measured
      (essentially simultaneously) during the crystallization process, yielding
      information on the complementary changes that occur in both the solid and liquid
      phases as a function of time. In this article, we present new results that
      highlight the application of our in situ NMR techniques to successfully unravel
      different aspects of crystallization processes, focusing on: (i) the application
      of a CLASSIC NMR approach to monitor competitive inclusion processes in solid
      urea inclusion compounds, (ii) exploiting liquid-state NMR to gain insights into
      co-crystal formation between benzoic acid and pentafluorobenzoic acid, and (iii)
      applications of in situ solid-state NMR for the discovery of new solid forms of
      trimethylphosphine oxide and L-phenylalanine. Finally, the article discusses a
      number of important fundamental issues relating to practical aspects, the
      interpretation of results and the future scope of these techniques, including:
      (i) an assessment of the smallest size of solid particle that can be detected in
      in situ solid-state NMR studies of crystallization, (ii) an appraisal of whether
      the rapid sample spinning required by the NMR measurement technique may actually
      influence or perturb the crystallization behaviour, and (iii) a discussion of
      factors that influence the sensitivity and time-resolution of in situ solid-state
      NMR experiments.

PMID- 25859758
TI  - Natural selection constrains neutral diversity across a wide range of species.
AB  - The neutral theory of molecular evolution predicts that the amount of neutral
      polymorphisms within a species will increase proportionally with the census
      population size (Nc). However, this prediction has not been borne out in
      practice: while the range of Nc spans many orders of magnitude, levels of genetic
      diversity within species fall in a comparatively narrow range. Although
      theoretical arguments have invoked the increased efficacy of natural selection in
      larger populations to explain this discrepancy, few direct empirical tests of
      this hypothesis have been conducted. In this work, we provide a direct test of
      this hypothesis using population genomic data from a wide range of taxonomically
      diverse species. To do this, we relied on the fact that the impact of natural
      selection on linked neutral diversity depends on the local recombinational
      environment. In regions of relatively low recombination, selected variants affect
      more neutral sites through linkage, and the resulting correlation between
      recombination and polymorphism allows a quantitative assessment of the magnitude
      of the impact of selection on linked neutral diversity. By comparing whole genome
      polymorphism data and genetic maps using a coalescent modeling framework, we
      estimate the degree to which natural selection reduces linked neutral diversity
      for 40 species of obligately sexual eukaryotes. We then show that the magnitude
      of the impact of natural selection is positively correlated with Nc, based on
      body size and species range as proxies for census population size. These results
      demonstrate that natural selection removes more variation at linked neutral sites
      in species with large Nc than those with small Nc and provides direct empirical
      evidence that natural selection constrains levels of neutral genetic diversity
      across many species. This implies that natural selection may provide an
      explanation for this longstanding paradox of population genetics. 

PMID- 25859761
TI  - Identification and Prioritization of Relationships between Environmental
      Stressors and Adverse Human Health Impacts.
AB  - BACKGROUND: There are > 80,000 chemicals in commerce with few data available
      describing their impacts on human health. Biomonitoring surveys, such as the
      NHANES (National Health and Nutrition Examination Survey), offer one route to
      identifying possible relationships between environmental chemicals and health
      impacts, but sparse data and the complexity of traditional models make it
      difficult to leverage effectively. OBJECTIVE: We describe a workflow to
      efficiently and comprehensively evaluate and prioritize chemical-health impact
      relationships from the NHANES biomonitoring survey studies. METHODS: Using a
      frequent itemset mining (FIM) approach, we identified relationships between
      chemicals and health biomarkers and diseases. RESULTS: The FIM method identified
      7,848 relationships between 219 chemicals and 93 health outcomes/biomarkers. Two
      case studies used to evaluate the FIM rankings demonstrate that the FIM approach
      is able to identify published relationships. Because the relationships are
      derived from the vast majority of the chemicals monitored by NHANES, the
      resulting list of associations is appropriate for evaluating results from
      targeted data mining or identifying novel candidate relationships for more
      detailed investigation. CONCLUSIONS: Because of the computational efficiency of
      the FIM method, all chemicals and health effects can be considered in a single
      analysis. The resulting list provides a comprehensive summary of the
      chemical/health co-occurrences from NHANES that are higher than expected by
      chance. This information enables ranking and prioritization on chemicals or
      health effects of interest for evaluation of published results and design of
      future studies. CITATION: Bell SM, Edwards SW. 2015. Identification and
      prioritization of relationships between environmental stressors and adverse human
      health impacts. Environ Health Perspect 123:1193-1199;
      http://dx.doi.org/10.1289/ehp.1409138.

PMID- 25859762
TI  - A biokinetic model for systemic technetium in adult humans.
AB  - This paper reviews biokinetic data for technetium and proposes a biokinetic model
      for systemic technetium in adult humans. The development of parameter values
      focuses on data for pertechnetate TcO(-)(4) the most commonly encountered form of
      technetium and the form expected to be present in body fluids. The model is
      intended as a default model for occupational or environmental intake of
      technetium, i.e. applicable in the absence of form- or site-specific information.
      Tissues depicted explicitly in the model include thyroid, salivary glands,
      stomach wall, right colon wall, liver, kidneys, and bone. Compared with the
      ICRP's current biokinetic model for occupational or environmental intake of
      technetium (ICRP 1993, 1994), the proposed model provides a more detailed and
      biologically realistic description of the systemic behaviour of technetium and is
      based on a broader set of experimental and medical data. For acute input of
      (99m)Tc (T(1/2) = 6.02 h) to blood, the ratios of cumulative (time-integrated)
      activity predicted by the current ICRP model to that predicted by the proposed
      model range from 0.4-7 for systemic regions addressed explicitly in both models.
      For acute input of (99)Tc (T(1/2) = 2.1 * 10(5) year) to blood, the corresponding
      ratios range from 0.2-30.

PMID- 25859763
TI  - Prediction of working memory performance in schizophrenia by plasma ratio of
      clozapine to N-desmethylclozapine.
AB  - OBJECTIVE: Clozapine's potent antagonism of muscarinic M1 receptors is thought to
      worsen working memory deficits associated with schizophrenia. In contrast, its
      major metabolite, N-desmethylclozapine (NDMC), is thought to enhance working
      memory via its M1 receptor agonist activity. The authors hypothesized that the
      ratio of serum clozapine and NDMC concentrations would be inversely associated
      with working memory performance in schizophrenia. METHOD: Thirty patients with
      schizophrenia or schizoaffective disorder who were receiving clozapine
      monotherapy at bedtime completed the MATRICS Consensus Cognitive Battery (MCCB)
      on the day their blood was collected to assess concentrations of clozapine and
      NDMC as well as serum anticholinergic activity. RESULTS: The clozapine/NDMC ratio
      was significantly and negatively associated with working memory performance after
      controlling for age, gender, education, and symptom severity. No significant
      associations were found between individual clozapine and NDMC concentrations and
      working memory performance. Serum anticholinergic activity was significantly
      associated with clozapine concentration, but not with working memory performance
      or NDMC concentration. No significant associations were found between any
      pharmacological measure and performance on other MCCB cognitive domains.
      CONCLUSIONS: This hypothesis-driven study confirms that clozapine/NDMC ratio is a
      strong predictor of working memory performance in patients with schizophrenia.
      This finding suggests that manipulating the clozapine/NDMC ratio could enhance
      cognition in patients with schizophrenia treated with clozapine. It also supports
      the study of procholinergic agents, such as M1 receptor-positive allosteric
      modulators, to enhance cognition in schizophrenia.

PMID- 25859765
TI  - Improving child outcomes through maternal mental health interventions.
AB  - This commentary will provide a general overview of the public health
      considerations of maternal mental illness, both from a global perspective as well
      as from the South African context. The paper will outline the consequences of
      maternal mental illness for mothers as well as their offspring, through the life
      stages from pregnancy until adulthood. The paper then describes the Perinatal
      Mental Health Project (PMHP), an intervention that addresses maternal mental
      health in Cape Town, South Africa. The evidence emerging from this example
      contributes to the case for integrating maternal mental health into the
      mainstream health environment. 

PMID- 25859766
TI  - Challenges in international collaboration in child and adolescent psychiatry.
AB  - International collaboration in child and adolescent psychiatry has historically
      been weak and fragmented. The field has also lagged in developing remedies for
      improving collaboration. This article identifies barriers to successful
      collaboration and examines problems in the areas of finance, professional
      development, knowledge dissemination, professional organisations, public policy
      and the political environment, priority setting, nomenclature, as well as ethical
      challenges. The article then identifies some promising initiatives and proposes
      solutions to improve international collaboration in child and adolescent mental
      health. 

PMID- 25859767
TI  - Lifestyles and routine activities of South African teenagers at risk of being
      trafficked for involuntary prostitution.
AB  - The United Nations estimates that 79% of teenage girls trafficked globally every
      year are forced into involuntary prostitution. About 247 000 South African
      children work in exploitative conditions; about 40 000 South African female
      teenagers work as prostitutes. This paper investigates lifestyles and routine
      activities of teenagers at risk of being trafficked for involuntary prostitution.
      The key concepts involuntary prostitution, intergenerational sex and exploitative
      conditions are defined in relation to the lifestyles and routine activities of
      South African female teenagers. Human trafficking for involuntary prostitution is
      described, based on a literature review. Lifestyle exposure and routine
      activities theories help to explain the potential victimisation of these
      teenagers in human trafficking for involuntary prostitution. Actual lifestyle and
      routine activities of South African teenagers and risky behaviours (substance
      abuse, intergenerational sex and child prostitution) are discussed as factors
      that make teens vulnerable to such trafficking. This paper recommends that human
      trafficking prevention efforts (awareness programmes and information campaigns)
      be directed at places frequented by human traffickers and teenagers in the
      absence of a capable guardian to reduce victimisation, as traffickers analyse the
      lifestyles and routine activities of their targets. South Africa should also
      interrogate entrenched practices such as intergenerational sex. 

PMID- 25859764
TI  - Randomized Trial of Cognitive-Behavioral Therapy Versus Light Therapy for
      Seasonal Affective Disorder: Acute Outcomes.
AB  - OBJECTIVE: Whereas considerable evidence supports light therapy for winter
      seasonal affective disorder (SAD), data on cognitive-behavioral therapy for SAD
      (CBT-SAD) are promising but preliminary. This study estimated the difference
      between CBT-SAD and light therapy outcomes in a large, more definitive test.
      METHOD: The participants were 177 adults with a current episode of major
      depression that was recurrent with a seasonal pattern. The randomized clinical
      trial compared 6 weeks of CBT-SAD (N=88) and light therapy (N=89). Light therapy
      consisted of 10,000-lux cool-white florescent light, initiated at 30 minutes each
      morning and adjusted according to a treatment algorithm based on response and
      side effects. CBT-SAD comprised 12 sessions of the authors' SAD-tailored protocol
      in a group format and was administered by Ph.D. psychologists in two 90-minute
      sessions per week. Outcomes were continuous scores on the Structured Interview
      Guide for the Hamilton Rating Scale for Depression-SAD Version (SIGH-SAD,
      administered weekly) and Beck Depression Inventory-Second Edition (BDI-II,
      administered before treatment, at week 3, and after treatment) and posttreatment
      remission status based on cut points. RESULTS: Depression severity measured with
      the SIGH-SAD and BDI-II improved significantly and comparably with CBT-SAD and
      light therapy. Having a baseline comorbid diagnosis was associated with higher
      depression scores across all time points in both treatments. CBT-SAD and light
      therapy did not differ in remission rates based on the SIGH-SAD (47.6% and 47.2%,
      respectively) or the BDI-II (56.0% and 63.6%). CONCLUSIONS: CBT-SAD and light
      therapy are comparably effective for SAD during an acute episode, and both may be
      considered as treatment options.

PMID- 25859768
TI  - Exploring high school learners' perceptions of bullying.
AB  - OBJECTIVE: Learners' perceptions of aspects of school life that are sufficiently
      serious to interfere with their schoolwork were investigated. Bullying was a form
      of behaviour that was singled out for inclusion and further exploration in the
      study. METHOD: Learners from three coeducational Western Cape Education
      Department schools were surveyed: 414 Grade 8 and 474 Grade 9 learners completed
      an anonymous, voluntary self-report questionnaire. RESULTS: Factors identified as
      most frequently interfering with their schoolwork included classmates not
      listening in class, feeling overwhelmed by schoolwork, teacher absenteeism, and
      verbal fighting. When asked specifically about bullying, 40% of learners
      indicated that they frequently experienced bullying at school-although they
      ranked it as much lower when compared to other potentially problematic school
      experiences. Furthermore, although the majority of learners indicated they
      thought teachers considered bullying a problem, few felt there was anything that
      school staff could do to counteract bullying effectively. CONCLUSIONS: These
      findings suggest that learners perceive bullying as an unavoidable part of school
      experience and have normalised this aggressive behaviour.

PMID- 25859769
TI  - Predicting HIV risk using a locus of control-based model among university
      students.
AB  - OBJECTIVE: The purpose of the study was to predict HIV risk using a locus of
      control-based intervention. The locus of control-based variables that were used
      in this study were social systems control, self-control, fatalism and achievement
      oriented behaviour. The study sample was made up of 257 university students whose
      ages ranged from 17-20 years. All the students were black. METHOD: The study
      assessed participants' perceived health control perceptions using Rotter's locus
      of control scale, social systems control scale, self-control scale, fatalism
      scale, the intellectual responsibility questionnaire and HIV risk assessment
      questionnaire. The study performed correlational and linear regression analyses
      using statistical software SAS to establish the relationship between locus of
      control-based factors and HIV risk. RESULTS: The results showed significant
      correlations between locus of control-based variables and HIV risk. The locus of
      control-based model significantly predicted variance in HIV risk. CONCLUSION:
      Directions for future research on the relationship between locus of control-based
      interventions and HIV risk could focus on the development of locus of control
      based HIV risk reduction interventions in South African universities.

PMID- 25859770
TI  - Bullying boys: the traumatic effects of bullying in male adolescent learners.
AB  - OBJECTIVE: This study investigated the nature and extent of the relationship
      between bullying and trauma among male adolescent learners. Trauma was
      operationalised through the multiple constructs of post-traumatic stress,
      anxiety, depression, dissociation and anger. METHOD: In this quantitative study,
      two objective measures were administered (viz. the Olweus Bullying/ Victimisation
      Scale and the Trauma Symptom Checklist for children) to a sample of male
      adolescent learners between the ages of 12 and 17, from a South African male-only
      high school (n = 486). RESULTS AND DISCUSSION: Statistical analysis
      (correlational analysis and MANOVA) produced evidence to suggest that there was a
      statistically significant relationship between bullying and trauma, and this was
      strongest for the victim role. The relationship between bullying and trauma was
      dependent on the frequency of bullying; as the frequency of being bullied
      increased so too did the mean scores of all the five trauma subscales. In
      general, the findings indicated that learners presented with elevated levels of
      internalising trauma outcomes. Depression demonstrated the highest correlation
      with the victim role, followed by Posttraumatic stress. In addition, 22.4% of
      learners could be clinically and sub-clinically diagnosed with post-traumatic
      stress and 21.0% with dissociation. Overall, the findings corroborate the
      argument that repetitive stressful events (such as bullying) are related to
      symptom-clusters of ongoing trauma.

PMID- 25859771
TI  - The challenge of treating conduct disorder in low-resourced settings: rap music
      to the rescue.
AB  - Conduct disorder is one of the most frequent serious childhood problems that
      present for treatment in community clinic settings. Evidence-based treatments for
      conduct disorder are intensive and require considerable resources to implement.
      In low-resourced contexts it is often not feasible to implement evidence-based
      treatments in their current form, which poses significant challenges for
      clinicians attempting to treat children in these settings. This article explores
      these challenges using a case study of the treatment of a young adolescent boy
      with a short-term multisystem intervention where rap music was employed as a
      powerful tool to facilitate an empathic connection in therapy and as a projective
      technique to explore underlying emotional difficulties. 

PMID- 25859772
TI  - Eating disorders.

PMID- 25859773
TI  - Cognitive-behavioural interventions for emotional and behavioural disorders:
      school-based practice.

PMID- 25859775
TI  - Journal abstracts from current research in the field of child and adolescent
      mental health.

PMID- 25859774
TI  - Anxiety: cognitive behaviour therapy with children and young people.

PMID- 25859776
TI  - Modular synthesis of heparin-related tetra-, hexa- and octasaccharides with
      differential o-6 protections: programming for regiodefined 6-o-modifications.
AB  - Heparin and heparan sulphate (H/HS) are important members of the
      glycosaminoglycan family of sugars that regulate a substantial number of
      biological processes. Such biological promiscuity is underpinned by
      hetereogeneity in their molecular structure. The degree of O-sulfation,
      particularly at the 6-position of constituent D-GlcN units, is believed to play a
      role in modulating the effects of such sequences. Synthetic chemistry is
      essential to be able to extend the diversity of HS-like fragments with defined
      molecular structure, and particularly to deconvolute the biological significance
      of modifications at O6. Here we report a synthetic approach to a small matrix of
      protected heparin-type oligosaccharides, containing orthogonal D-GlcN O-6
      protecting groups at programmed positions along the chain, facilitating access
      towards programmed modifications at specific sites, relevant to sulfation or
      future mimetics. 

PMID- 25859777
TI  - Evaluation of the hypoglycemic effects of flavonoids and extracts from Jatropha
      gossypifolia L.
AB  - Jatropha gossypifolia L. (Euphorbiaceae) is a plant widely used in the treatment
      of type 2 diabetes mellitus (T2DM), but there are few scientific reports
      validating its activity in this area. In this work and through a bioguided assay,
      a crude extract stimulated glucose uptake in C2C12 myotubes up to 30%, thereby
      reducing insulin resistance induced by fatty acids compared to the basal control.
      A chromatographic fraction applied intraperitoneally (IP) in mice reduced glucose
      by 42% in a mouse model of T2DM, after administration of 10 doses during 20 days.
      A flavanone was purified from this active fraction and its structure was assigned
      by 1H- and 13C-NMR (1D and 2D) and MS. This compound retains the previously
      reported activity, stimulating in vitro the glucose uptake in a concentration
      dependent manner. This study indicates that Jatropha gossypifolia L. extracts
      enhance glucose uptake in cultured myotubes and adipocytes and also improving
      glucose tolerance in an in vivo model. 

PMID- 25859778
TI  - Biological activities and cytotoxicity of diterpenes from Copaifera spp.
      Oleoresins.
AB  - Copaifera spp. are Amazonian species widely studied and whose oleoresins are used
      by local people for various medicinal purposes. However, a detailed study of the
      activity of the main phytochemical components of these oleoresins remains to be
      done. Here, we studied the cytotoxicity and in vitro anti-inflammatory effects of
      six diterpene acids: copalic, 3-hydroxy-copalic, 3-acetoxy-copalic, hardwickiic,
      kolavic-15-metyl ester, and kaurenoic, isolated from the oleoresins of Copaifera
      spp. The diterpenes did not show cytotoxicity in normal cell lines, nor did they
      show significant changes in viability of tumoral line cells. The 3-hydroxy
      copalic was able to inhibit the enzyme tyrosinase (64% +/- 1.5%) at 250 uM. The
      kolavic-15-metyl ester at 200 uM showed high inhibitory effect on lipoxygenase
      (89.5% +/- 1.2%). Among the diterpenes tested, only kaurenoic and copalic acids
      showed significant hemolytic activities with 61.7% and 38.4% at 100 uM,
      respectively. In addition, it was observed that only the copalic acid (98.5% +/-
      1.3%) and hardwickiic acid (92.7% +/- 4.9%) at 100 mM inhibited nitric oxide
      production in macrophages activated by lipopolysaccharide. In this assay, the
      diterpenes did not inhibit tumor necrosis factor-alpha production. The acids
      inhibited the production of IL-6, 3-acetoxy-copalic (23.8% +/- 8.2%), kaurenoic
      (11.2% +/- 5.7%), kolavic-15-methyl ester (17.3% +/- 4.2%), and copalic (4.2% +/-
      1.8%), respectively, at 25 uM. The kaurenoic, 3-acetoxy-copalic and copalic acids
      increased IL-10 production. This study may provide a basis for future studies on
      the therapeutic role of diterpenic acids in treating acute injuries such as
      inflammation or skin disorders. 

PMID- 25859779
TI  - Covalent modification of human serum albumin by the natural sesquiterpene lactone
      parthenolide.
AB  - The reactivity of parthenolide (PRT), a natural sesquiterpene lactone from
      Tanacetum parthenium (Asteraceae), with human serum albumin (HSA) was studied by
      UHPLC/+ESI-QqTOF MS analysis after tryptic digestion of albumin samples after
      incubation with this compound. It was found that the single free cysteine
      residue, C34, of HSA (0.6 mM) reacted readily with PRT when incubated at
      approximately 13-fold excess of PRT (8 mM). Time-course studies with PRT and its
      11beta,13-dihydro derivative at equimolar ratios of the reactants revealed that
      PRT under the chosen conditions reacts preferably with C34 and does so
      exclusively via its alpha-methylene-gamma-lactone moiety, while the epoxide
      structure is not involved in the reaction. 

PMID- 25859780
TI  - Cu (II)-catalyzed asymmetric henry reaction with a novel C1-symmetric aminopinane
      derived ligand.
AB  - A novel C1-symmetric dinitrogen ligand was synthesized in high yield from
      commercially available (1R,2R,3R,5S)-(-)-isopinocampheylamine and 1-methyl-2
      imidazolecarboxaldehyde. In combination with Cu(OAc)2H2O, this new ligand promote
      the reaction between nitromethane and aliphatic aldehydes with high yields (up to
      97%) and moderate enantioselectivities (up to 67% ee). The reactions with
      benzaldehyde required prolonged reaction time that resulted in diminished yields,
      but accompanied with ee-values in the 55%-76% range. 

PMID- 25859782
TI  - Determination of the primary molecular target of 1,2,4-triazole-ciprofloxacin
      hybrids.
AB  - We have synthesized and examined the antibacterial activity, toxicity and
      affinity towards bacterial type II topoisomerases of a series of 1,2,4-triazole
      ciprofloxacin hybrids. A number of these compounds displayed enhanced activity
      against Gram-positive and Gram-negative bacteria when compared to ciprofloxacin.
      The toxic concentrations of the obtained derivatives, evaluated on HEK-293 cells
      using MTT assay, were much higher than concentrations required to produce
      antibacterial effect. Finally, the results of enzymatic studies showed that the
      analyzed compounds demonstrated other preferences as regards primary and
      secondary molecular targets than ciprofloxacin. 

PMID- 25859781
TI  - Model organisms in the fight against muscular dystrophy: lessons from drosophila
      and Zebrafish.
AB  - Muscular dystrophies (MD) are a heterogeneous group of genetic disorders that
      cause muscle weakness, abnormal contractions and muscle wasting, often leading to
      premature death. More than 30 types of MD have been described so far; those most
      thoroughly studied are Duchenne muscular dystrophy (DMD), myotonic dystrophy type
      1 (DM1) and congenital MDs. Structurally, physiologically and biochemically, MDs
      affect different types of muscles and cause individual symptoms such that genetic
      and molecular pathways underlying their pathogenesis thus remain poorly
      understood. To improve our knowledge of how MD-caused muscle defects arise and to
      find efficacious therapeutic treatments, different animal models have been
      generated and applied. Among these, simple non-mammalian Drosophila and zebrafish
      models have proved most useful. This review discusses how zebrafish and
      Drosophila MD have helped to identify genetic determinants of MDs and design
      innovative therapeutic strategies with a special focus on DMD, DM1 and congenital
      MDs. 

PMID- 25859783
TI  - Hepatoprotective triterpene saponins from the roots of Glycyrrhiza inflata.
AB  - Two novel oleanane-type triterpene saponins, licorice-saponin P2 (1) and licorice
      saponin Q2 (3), together with nine known compounds 2, 4-11, have been isolated
      from the water extract of the roots of Glycyrrhiza inflata. The structures of
      these compounds were elucidated on the basis of spectroscopic analysis, including
      2D-NMR experiments (1H-1H COSY, HSQC, HMBC and ROESY). In in vitro assays,
      compounds 2-4, 6 and 11 showed significant hepatoprotective activities by
      lowering the ALT and AST levels in primary rat hepatocytes injured by D
      galactosamine (D-GalN). In addition, compounds 2-4, 6, 7 and 11 were found to
      inhibit the activity of PLA2 with IC50 values of 6.9 MUM, 3.6 MUM, 16.9 MUM, 27.1
      MUM, 32.2 MUM and 9.3 MUM, respectively, which might be involved in the
      regulation of the hepatoprotective activities observed. 

PMID- 25859784
TI  - Synthesis, photophysical characterization, and photoinduced antibacterial
      activity of methylene blue-loaded amino- and mannose-targeted mesoporous silica
      nanoparticles.
AB  - Over the last 20 years, the number of pathogenic multi-resistant microorganisms
      has grown steadily, which has stimulated the search for new strategies to combat
      antimicrobial resistance. Antimicrobial photodynamic therapy (aPDT), also called
      photodynamic inactivation, is emerging as a promising alternative to treatments
      based on conventional antibiotics. We have explored the effectiveness of
      methylene blue-loaded targeted mesoporous silica nanoparticles (MSNP) in the
      photodynamic inactivation of two Gram negative bacteria, namely Escherichia coli
      and Pseudomonas aeruginosa. For E. coli, nanoparticle association clearly reduced
      the dark toxicity of MB while preserving its photoinactivation activity. For P.
      aeruginosa, a remarkable difference was observed between amino- and mannose
      decorated nanoparticles. The details of singlet oxygen production in the
      nanoparticles have been characterized, revealing the presence of two populations
      of this cytotoxic species. Strong quenching of singlet oxygen within the
      nanoparticles is observed. 

PMID- 25859785
TI  - Silver nanopartical over AuFON substrate for enhanced raman readout and their
      application in pesticide monitoring.
AB  - Surface-enhanced Raman detection of thiram is demonstrated by using Ag
      nanoparticles (Ag NPs) on Au film over nanosphere (AuFON) substrate as the hybrid
      substrate. The SERS signal of the Ag NPs attached to solid supports is studied.
      The close coupling together of thousands of Ag NPs on AuFON leads to the
      generation of hot spots for SERS. The Ag NPs on AuFON can be applied to detect
      rhodamine-6G (R6G) with the detection limitation of 10-11 M and the pesticide
      thiram in acetone with a detection limit of as low as 0.24 ppm, which is much
      lower than the maximal residue limit (MRL) of 7 ppm in fruit prescribed by the
      U.S. Environmental Protection Agency (EPA). The hybrid substrates are shown to be
      highly sensitive for the detection of thriam, which produce highly enhanced Raman
      signals with good uniformity and reproducibility due to having plenty of hot
      spots on its surface. 

PMID- 25859787
TI  - Determinants of age at sexual debut and associated risks among South African
      youths.
AB  - The research uses data from a representative national survey to explore the
      determinants of age at sexual debut among South African youths in the age group
      15-24 years. A random sample of 5 708 youths were interviewed and 92% responded
      to questions on whether or not they had ever had sex and their age at first sex
      for those who had. The research used survival analyses techniques to combine
      'current status data' and 'recall data' for respondents who reported ever having
      had sex. The females were more likely than the males to report ever having had
      sex (p<=0.001). The median age at sexual debut was 18 years for both males and
      females. The hazard ratio pertaining to early sexual debut was 0.81-times less
      for those in the age group 15-19 as compared to those in the age group 20-24
      (p<=0.001). Age, race, geographical location, and level of education were found
      to be important determinants of age at sexual debut. The 'hazards of sexual
      debut' (theta=0.112; p<=0.001) varied significantly between geographical areas
      (rural or urban). Youths with an earlier age of sexual debut were less likely to
      have used condoms, a behaviour which increases their risk of HIV infection. HIV
      prevalence was consistently higher among the females than among the males. We
      recommend that HIV-prevention interventions target community sets rather than
      only individuals at higher risk of exposure to HIV. 

PMID- 25859786
TI  - Thermoresponsive Photonic Crystal: Synergistic Effect of Poly(N
      isopropylacrylamide)-co-acrylic Acid and Morpho Butterfly Wing.
AB  - In this work, we report a simple method to fabricate smart polymers engineered
      with hierarchical photonic structures of Morpho butterfly wing to present high
      performance that are capable of color tunability over temperature. The materials
      were assembled by combining functional temperature responsivity of poly(N
      isopropylacrylamide)-co-acrylic acid (PNIPAm-co-AAc) with the biological photonic
      crystal (PC) structure of Morpho butterfly wing, and then the synergistic effect
      between the functional polymer and the natural PC structure was created. Their
      cooperativity is instantiated in the phase transition of PNIPAm-co-AAc (varying
      with the change of temperature) that can alter the nanostructure of PCs, which
      further leads to the reversible spectrum response property of the modified
      hierarchical photonic structures. The cost-effective biomimetic technique
      presented here highlights the bright prospect of fabrication of more stimuli
      responsive functional materials via coassembling smart polymers and
      biohierarchical structures, and it will be an important platform for the
      development of nanosmart biomaterials. 

PMID- 25859788
TI  - Extraction of non-timber forest products as a coping strategy for HIV/AIDS
      afflicted rural households in south-eastern Zimbabwe.
AB  - This article examines the role of the extraction of non-timber forest products
      (NTFPs) as a coping strategy in response to HIV/AIDS-related economic shocks
      among rural households in the semi-arid Sengwe communal lands in south-eastern
      Zimbabwe. Using panel data for 200 households in 2008 and 2009, an econometric
      analysis revealed NTFP extraction as an important ex-post coping mechanism for
      the HIV/AIDS-afflicted households. Many of the households responded to HIV
      related economic crises by increasing NTFP extraction to smooth both consumption
      and income. On average, the additional income from NTFPs offset about 48% of a
      household's income shortfalls due to the impact of HIV or AIDS. The importance of
      NTFPs as an economic safety-net for households depends more on the timing of
      extraction than on the magnitude (i.e. as a share of total household
      contribution). Hence, sustainable forest management is of great value for semi
      arid tropical areas, such as the Sengwe communal lands, which are hard hit by the
      HIV epidemic. Consequently, government and other stakeholders would be well
      advised to implement programmes that reduce pressure on the forest resources,
      such as by introducing other incomegenerating enterprises like raising small
      livestock, while improvements in access to education and healthcare will further
      help the rural poor cope with HIV/AIDS-induced economic crises. 

PMID- 25859789
TI  - The significance of gathering wild orchid tubers for orphan household livelihoods
      in a context of HIV/AIDS in Tanzania.
AB  - We investigated the role of gathering and selling the edible tubers of wild
      orchids by children orphaned by AIDS as one of their livelihood strategies,
      through a household survey administered to 152 households in three villages in
      the Southern Highlands of Tanzania during 2006 and 2007. Additionally, several
      household heads were selected as case studies and subjected to an in-depth life
      history interview. Overall, most households in the study villages were very poor.
      We made comparisons within a total sample of 57 households headed by children
      orphaned by AIDS, 43 adult female-headed AIDS-affected households, and 52 adult
      male-headed non-AIDS-affected households in terms of food security and wealth
      outcomes after engaging in orchid tuber-gathering activities. The findings reveal
      that the majority of the orphan heads of households regarded the gathering and
      selling of wild orchid tubers as the best option for satisfying their basic
      needs. This category of households gathered more orchid tubers than the male
      headed non-AIDS-affected households but not more than the female-headed AIDS
      affected households. Children in these households spent more time on tuber
      gathering activities than did members of the other households but had fewer
      household assets. Almost all the orphan-headed households depended on the cash
      obtained from selling orchid tubers to purchase food throughout the year.
      However, we surmise that gathering and selling wild orchid tubers fails to pull
      these children out of poverty and functions merely as a survival strategy. 

PMID- 25859790
TI  - The new female condom (FC2) in Uganda: perceptions and experiences of users and
      their sexual partners.
AB  - The new version of the female condom (FC2) was introduced in Uganda in October
      2009, following an unsuccessful female condom programme begun in 1998. The
      failure of the earlier programme was partly attributed to low acceptance of the
      first type of female condom (FC1). We evaluated the acceptability of FC2 and the
      experiences of users and their sexual partners. This was a qualitative cross
      sectional evaluation. We conducted 16 in-depth interviews with FC2 users (8 women
      and 8 male partners). We also conducted eight focus group discussions with women
      who used FC2, and 22 key informant interviews with service providers. All the
      female users appreciated FC2 as a tool to empower them to avoid sexually
      transmitted infections (STIs) and unwanted pregnancies. They liked FC2 because it
      has no smell, is not noisy, and does not rupture easily. The men also liked FC2
      because of its soft texture and lubrication. Some women found FC2 insertion
      cumbersome, while others feared that it would slip in on itself during sex.
      Concurrent use of male condoms with FC2 and the reuse of FC2 were also mentioned.
      Providers reported a high demand for FC2; their main challenges were inadequate
      supplies and distribution mechanisms. This evaluation shows generally high
      acceptance of FC2. The experiences of users and their partners were largely
      positive, although some fears and incorrect practices arose. FC2 should be added
      to the existing HIV/STI-prevention and family-planning options in Uganda and
      other countries, with sufficient training and support to ensure correct use. 

PMID- 25859791
TI  - Predictors of sexual-risk behaviour and HIV-preventive practices among university
      students in Ethiopia.
AB  - A cross-sectional study design was used to assess sexual-risk behaviour and HIV
      preventive practices among students at Hawassa University, Ethiopia, in 2009.
      Among 1 220 students eligible for the study, approximately 29% reported
      experience of sex (36.3% of the males and 9.3% of the females). Of the total
      sexually active respondents, 67.1% had begun sexual activity while still in
      secondary school. For the previous 12-month period, 42.1% said they did not use
      condoms during the last sexual encounter, 46.1% of the males claimed having had
      sex with 'bar ladies,' and 39% said they had an active symptom of a sexually
      transmitted infection (STI). Logistic regression analysis demonstrated a
      significant association of higher-risk sexual practices in the previous year with
      being female and having an income greater than US$30/month. Having multiple
      sexual partners was strongly associated with being female, having a monthly
      income greater than US$30, a sexual debut before age 18 and before attending
      university, ever having had sex for the sake of money, active STI symptoms, and
      attending nightclubs. Overall, the students reported sexual practices that were
      considerably unprotected; we surmise that this likely exposed approximately two
      fifths to STIs and nearly 10% to unplanned pregnancy. We conclude that to alter
      university students' sexual-risk behaviour, a great deal of relevant intervention
      should be carried out during earlier school years, and the observed link between
      a greater frequency of sexual-risk behaviour and higher income needs to be
      investigated. 

PMID- 25859792
TI  - Gender vulnerabilities, spousal abuse and the incidence of HIV in Lesotho:a case
      for an integrative rights-based approach.
AB  - The article posits that imbalances in gender relations are influencing two
      distinctive yet connected crises for women in Lesotho: the HIV epidemic and
      spousal abuse. The overarching premise is that as spousal abuse is increasingly
      recognised and as HIV infections spread, responses to the phenomenon do not
      reflect the related risks and consequences in married women's lives. This article
      underscores the nexus of connections between HIV and spousal abuse in Lesotho,
      identifying potential areas for pragmatic state-led responses. Applying a rights
      based approach, it assesses women's vulnerability to each problem at the
      individual, societal and programmatic levels, noting that there are both direct
      and underlying factors heightening risks for women. The article asks, what is the
      value added by a rights-based approach to the subject under discourse? And, how
      can a rights-based approach be translated into practical tools for planning,
      monitoring and evaluating projects and programmes aimed at tackling the
      multifaceted risks and challenges of HIV and spousal abuse confronting women in
      Lesotho? In response to these questions, the author identifies three trajectories
      of opportunities for an integrated, comprehensive response. The unmistakable
      anchor of the article's propositions is the rights-based approach. Although the
      discussion focuses on Lesotho, the implications for the broader African region
      cannot be overemphasised in light of commonly shared experiences pertaining to
      the severe difficulties posed by spousal abuse and HIV. 

PMID- 25859793
TI  - Depression underdiagnosis and the effects on quality of life in outpatients with
      HIV at a Nigerian university teaching hospital.
AB  - The study aimed to determine the frequency of depressive disorder in a sample of
      patients with HIV and its level of underdiagnosis by attending physicians. The
      study also explored the effect of depressive disorder on the quality of life
      (QOL) of patients with HIV. A sociodemographic questionnaire was administered to
      patients with HIV attending a medical out-patient clinic at Ahmadu Bello
      University Teaching Hospital, central northern Nigeria. The Center for
      Epidemiologic Studies Depression Scale (CES-D) was used to screen for depressive
      symptoms, and the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) was
      used to confirm the diagnosis of depressive disorder. The patients' medical
      records were screened for documentation of depressive symptoms or previous
      treatment with antidepressants by an attending physician. The World Health
      Organization Quality of Life assessment short version (WHOQOL-BREF) was used to
      measure six domains of QOL. A total of 310 patients with HIV participated in the
      study; of these, 14.2% (n = 44) met the diagnostic criteria for depressive
      disorder, according to the International Statistical Classification of Diseases
      and Related Health Problems 10th Revision (ICD-10). All of these cases of
      depressive disorder had not been previously recognised by any attending
      physician. Of the 310 participants, 58 (18.7%) had a 'poor' score and 252 (81.3%)
      had an 'average or above' score for overall QOL. Of the 44 with depressive
      disorder, 28 (63.6%) were among those with a poor score for overall QOL. A fairly
      similar pattern was observed for all the other domains, with patients with
      depressive disorder accounting for greater proportions of the participants with
      poor domain scores. Thus, the authors found that depression is common but seldom
      clinically recognised in people with HIV, and that it is associated with a
      reduction in quality of life. Identifying and treating depression in patients
      with HIV will improve functioning and general wellbeing. 

PMID- 25859794
TI  - Sexual-risk behaviour among sexually active first-year students at the University
      of the Western Cape, South Africa.
AB  - In South Africa, new HIV infections are concentrated among persons aged 15-24
      years. The university population falls within this age group and are prone to
      higher-risk behaviours that place them at risk of acquiring HIV. In a study to
      assess this risk among sexually active students, we classified higher-risk sexual
      behaviours as not using condoms at every instance of sex, having had more than
      one sexual partner during the preceding 12 months, a relatively young age at
      first sexual intercourse (7-16 years), and experience of sexual violence and/or
      transactional sex. In total, 796 first-year students at the University of the
      Western Cape in Cape Town, South Africa, completed a self-administered
      questionnaire in 2006. The sample included 263 sexually active, unmarried
      students, aged 16 to 24 years. The responses showed that 62% did not use a condom
      for every instance of sex, 39% had two or more sexual partners in the previous 12
      months, 53% had initiated sexual intercourse at a younger age (7-16 years), and
      2% had ever exchanged money or gifts for sexual intercourse. Eight percent of the
      respondents said they did not give their consent or permission at initiation of
      first sexual intercourse. One in every 10 respondents claimed that they had ever
      been forced to have sexual intercourse, and 4% said that they had ever forced
      someone to have sexual intercourse. The sexually active students who reported an
      earlier age of initiation of sexual intercourse and having only one sexual
      partner during the last year were more likely to not use a condom every time,
      whereas the sexually active students that had experienced initiation of sexual
      intercourse while in an older age group (17-24 years) and who had two or more
      sexual partners in the last year were more likely to use a condom every time.
      Sexually active university students are in need of particular HIV-prevention
      interventions given their tendencies for poor condom usage and having multiple
      sexual partners. 

PMID- 25859795
TI  - Correlates of highly active antiretroviral therapy adherence among urban
      Ethiopian clients.
AB  - There has been a massive expansion of highly active antiretroviral therapy
      (HAART) services in Ethiopia since 2005. To assess clients' self-reported
      adherence to HAART medication, a descriptive, comparative cross-sectional study
      was carried out among adults receiving HAART medication at the Zewditu Memorial
      Hospital ART clinic in Addis Ababa. Of 1 808 clients eligible for the study, 1
      722 agreed to participate. The data were collected over six weeks in February and
      March 2010. Ordered and binary logistic regression models were applied to analyse
      the data. The majority of participants were over age 30 years, most were females,
      and 90% had some formal education. More than half reported being 'extremely sure'
      about their ability to take most or all of their medication. Self-reported
      adherence to the medication was generally good, as 62% said they had never missed
      a dose. The most commonly cited reason for missing medication was being busy
      (57.5%). The odds of ever missing a dose of HAART were lower for males (adjusted
      odds ratio [AOR]: 1.44; 95% confidence interval [CI]: 1.15-1.79), older persons
      (AOR: 0.98; 95% CI: 0.97-0.99), and those who did not drink alcohol regularly.
      Similarly, the odds of being self-confident about taking the medication properly
      were higher for males and for those who did not drink alcohol regularly (AOR:
      0.48; 95% CI: 0.35-0.64). The odds of self-confidence in taking the medication
      were lower among those in lower income group. Those who reported an expenditure
      income of Birr 501-999 (AOR: 0.35; 95% CI: 0.24-0.49) or Birr 1 000-1 999 (AOR:
      0.41; 95% CI: 0.29-0.60) had less self-confidence in taking their medication
      properly as compared to those who had an expenditure income of Birr 2 000 or
      more. There is a need to design and implement targeted adherence interventions
      that could lead to better treatment outcomes. 

PMID- 25859796
TI  - Kenyan pastors' perspectives on communicating about sexual behaviour and HIV.
AB  - The article presents an analysis of in-depth interviews with 18 leaders of
      Christian churches in Nairobi, Kenya, regarding the content and context of
      messages they disseminate to their congregations about sexual behaviour and HIV.
      The content of messages was nearly consistent across the different denominations.
      However, three sorts of tensions were identified within pastoral communication
      about these topics: the need to discuss sex and HIV versus societal taboos
      against speaking about those issues from the pulpit; traditional cultural norms
      versus current lifestyles; and the ideals of abstinence and fidelity versus the
      reality of congregants' sexual behaviour. Although some of the religious leaders
      accepted the idea of condom use, no denominational patterns were noted on that
      subject, except with respect to Catholic priests. Pentecostal leaders were
      notable for describing proactive strategies to address both the ideal/real
      dilemma and the tension between church norms and current media content about
      sexuality and HIV. 

PMID- 25859797
TI  - The rise and fall of HIV prevalence in Zimbabwe: the social, political and
      economic context.
AB  - For more than 10 years Zimbabwe has experienced social, political and economic
      instability, including the near collapse in 2008 of its health system.
      Paradoxically, this period has also seen a fall in estimated HIV prevalence, from
      25.6% in 1996 to 13.7% in 2009. This article examines this development in a socio
      political and historical context. We focus on the complex interplay of migration,
      mortality, individual behaviour change, and economic patterns in shaping the
      presumed epidemiological waning of HIV prevalence in Zimbabwe and explore the
      evolution and management of the country's HIV/AIDS response. Our assessment of
      the role that the Zimbabwean state has played in this development leads to the
      conclusion that a decline in HIV prevalence has been as much an artefact of dire
      social, political and economic conditions as the outcome of deliberate
      interventions. Lastly, we propose the need to contextualise available
      epidemiological data through qualitative research into the social aspects of HIV
      and the everyday lives of individuals affected by it. 

PMID- 25859799
TI  - Editorial: update on inflammatory targets modulating atherogenesis.

PMID- 25859800
TI  - Vascular consequences of operculoinsular corticectomy for refractory epilepsy.
AB  - OBJECT: Surgery in the insular region is considered challenging because of its
      vascular relationships, the proximity of functional structures, and its deep
      location in the sylvian fissure. The authors report the incidence and
      consequences of ischemic lesions after operculoinsular corticectomy for
      refractory epilepsy. METHODS: The authors retrospectively reviewed the data of
      all patients who underwent an insular resection with or without an opercular
      resection for refractory epilepsy at their center. All patients underwent
      postoperative MRI, enabling a radiological analysis of the ischemic lesions as a
      result of the corticectomies. The resections were classified according to the
      location and extent of the insular corticectomy and the type of operculectomy.
      Each patient underwent clinical follow-up. RESULTS: Twenty patients underwent
      surgery. All patients underwent insular corticectomy with or without an
      operculectomy. Ischemic lesions were identified in 12 patients (60%). In these
      patients, 11 ischemic lesions (55%) were related to the insular corticectomy, and
      1 was related to the associated periinsular resection. The ischemic lesions
      associated with the insulectomies were typically located in the corona radiata
      running from the insula to the periventricular region. Nine patients (45%)
      developed a postoperative neurological deficit, among whom 6 (67%) had an insular
      corticectomy-related ischemic lesion. All reported neurological deficits were
      transient. Five patients (25%) had ischemic lesions without neurological deficit.
      CONCLUSIONS: Operculoinsular corticectomies are associated with ischemic lesions
      in approximately 60% of patients. However, given that no patient had a definitive
      postoperative deficit, these ischemic lesions have few clinical consequences.
      Therefore, this surgical procedure can be considered reasonably safe for the
      treatment of refractory epilepsy.

PMID- 25859798
TI  - Large Amounts of Reactivated Virus in Tears Precedes Recurrent Herpes Stromal
      Keratitis in Stressed Rabbits Latently Infected with Herpes Simplex Virus.
AB  - AIM: Recurrent herpetic stromal keratitis (rHSK), due to an immune response to
      reactivation of herpes simplex virus (HSV-1), can cause corneal blindness. The
      development of therapeutic interventions such as drugs and vaccines to decrease
      rHSK have been hampered by the lack of a small and reliable animal model in which
      rHSK occurs at a high frequency during HSV-1 latency. The aim of this study is to
      develop a rabbit model of rHSK in which stress from elevated temperatures
      increases the frequency of HSV-1 reactivations and rHSK. MATERIALS AND METHODS:
      Rabbits latently infected with HSV-1 were subjected to elevated temperatures and
      the frequency of viral reactivations and rHSK were determined. RESULTS: In an
      experiment in which rabbits latently infected with HSV-1 were subjected to ill
      defined stress as a result of failure of the vivarium air conditioning system,
      reactivation of HSV-1 occurred at over twice the normal frequency. In addition,
      60% of eyes developed severe rHSK compared to <1% of eyes normally. All episodes
      of rHSK were preceded four to five days prior by an unusually large amount of
      reactivated virus in the tears of that eye and whenever this unusually large
      amount of reactivated virus was detected in tears, rHSK always appeared 4-5 days
      later. In subsequent experiments using well defined heat stress the reactivation
      frequency was similarly increased, but no eyes developed rHSK. CONCLUSIONS: The
      results reported here support the hypothesis that rHSK is associated not simply
      with elevated reactivation frequency, but rather with rare episodes of very high
      levels of reactivated virus in tears 4-5 days earlier.

PMID- 25859801
TI  - Clinical features and disease progression in moyamoya disease patients with
      Graves disease.
AB  - OBJECT: The present study aimed to clarify the incidence and clinical features of
      disease progression in adult moyamoya disease (MMD) patients with Graves disease
      (GD) for better management of these patients. METHODS: During the past 18 years,
      320 adult Chinese patients at West China Hospital were diagnosed with MMD, and 29
      were also diagnosed with GD. A total of 170 patients (25 with GD; 145 without GD)
      were included in this study and were followed up. The mean follow-up was 106.4 +/
      48.6 months (range 6-216 months). The progression of the occlusive lesions in
      the major intracranial arteries was measured using cerebral angiography and was
      evaluated according to Suzuki's angiographic staging. Information about
      cerebrovascular strokes was obtained from the records of patients' recent
      clinical visits. Both angiographic progression and strokes were analyzed to
      estimate the incidences of angiographic progression and strokes using Kaplan
      Meier analysis. A multivariate logistic regression model was used to test the
      effects of sex, age at MMD onset, disease type, strokes, and GD on the onset of
      MMD progression during follow-up. RESULTS: During follow-up, the incidence of
      disease progression in MMD patients with GD was significantly higher than in
      patients without GD (40.0% vs 20.7%, respectively; p = 0.036). The interval
      between initial diagnosis and disease progression was significantly shorter in
      MMD patients with GD than in patients without GD (p = 0.041). Disease progression
      occurred in both unilateral MMD and bilateral MMD, but the interval before
      disease progression in patients with unilateral disease was significantly longer
      than in patients with bilateral disease (p = 0.021). The incidence of strokes in
      MMD patients with GD was significantly higher than in patients without GD (48% vs
      26.2%, respectively; p = 0.027). The Kaplan-Meier survival curve showed
      significant differences in the incidence of disease progression (p = 0.038, log
      rank test) and strokes (p = 0.031, log-rank test) between MMD patients with GD
      and those without GD. Multivariate analysis suggested that GD may contribute to
      disease progression in MMD (OR 5.97, 95% CI 1.24-33.76, p = 0.043). CONCLUSIONS:
      The incidence of disease progression in MMD patients with GD was significantly
      higher than that in MMD patients without GD, and GD may contribute to disease
      progression in MMD patients. The incidence of strokes was significantly higher in
      MMD patients with GD than in patients without GD. Management guidelines for MMD
      patients with GD should be developed.

PMID- 25859802
TI  - Apoplexy of pituitary adenomas: the perfect storm.
AB  - OBJECT: Pituitary adenomas occasionally undergo infarction, apoplexy, which often
      destroys much of the tumor. It is well known that apoplexy can be precipitated by
      several acute factors, including cardiac surgery, other types of surgery, trauma,
      insulin infusion, and stimulation with administration of hypothalamic releasing
      factors. METHODS: The prior focus on mechanisms underlying pituitary apoplexy has
      been on these acute events. Less attention has been given to the endogenous
      features of pituitary tumors that make them susceptible to spontaneous
      infarction, despite that most pituitary apoplexy occurs in the absence of a
      recognized precipitating event. The authors examine intrinsic features of
      pituitary adenomas that render them vulnerable to apoplexy-features such as high
      metabolic demand, paucity of angiogenesis, and sparse vascularity, qualities that
      have previously not been linked with apoplexy-and argue that it is these features
      of adenomas that underlie their susceptibility to spontaneous infarction. The
      sensitivity of freshly cultured pituitary adenomas to hypoglycemia is assessed.
      RESULTS: Adenomas have high metabolic demand, limited angiogenesis, and reduced
      vessel density compared with the normal gland. Pituitary adenoma cells do not
      survive in the presence of reduced or absent concentrations of glucose.
      CONCLUSIONS: The authors propose that the frequent ischemic infarction of
      pituitary adenomas is the product of intrinsic features of these tumors. These
      endogenous qualities create a tenuous balance between high metabolic demand and
      marginal tissue perfusion. Thus, the tumor is vulnerable to spontaneous
      infarction or to acute ischemia by any event that acutely alters the balance
      between tumor perfusion and tumor metabolism, events such as acute systemic
      hypotension, abruptly decreased supply of nutrients, hypoglycemia with insulin
      administration, or increase in the tumor's metabolic demand due to administration
      of hypothalamic releasing factors. It may be possible to take advantage of these
      intrinsic features of pituitary adenomas by using aspects of this vulnerability
      for development of new approaches for treatment.

PMID- 25859803
TI  - Cerebral hemodynamic disturbance in dural arteriovenous fistula with retrograde
      leptomeningeal venous drainage: a prospective study using (123)I-iodoamphetamine
      single photon emission computed tomography.
AB  - OBJECT: The severity of cerebral hemodynamic disturbance caused by retrograde
      leptomeningeal venous drainage (RLVD) of a dural arteriovenous fistula (dAVF) is
      related to neurological morbidity and unfavorable outcome. However, the cerebral
      hemodynamics of this disorder have not been elucidated well. The aim of this
      study was to assess the relationship between the cerebral venous congestive
      encephalopathy represented as a high-intensity area (HIA) on T2-weighted MR
      images and the cerebral hemodynamics examined by (123)I-iodoamphetamine (IMP)
      single photon emission computed tomography (SPECT), as well as the predictive
      value of (123)I-IMP SPECT for the development and reversibility of venous
      congestion encephalopathy. METHODS: Based on the pre- and posttreatment T2 HIAs
      associated with venous congestion encephalopathy, patients were divided into 3
      groups: a normal group, an edema group, and an infarction group. The regional
      cerebral blood flow (rCBF) at the region with RLVD was analyzed by (123)I-IMP
      SPECT, and the results were compared among the groups. RESULTS: There were 11, 6,
      and 3 patients in the normal, edema, and infarction groups, respectively. No
      patients in the normal group showed any symptoms related to venous congestion. In
      contrast, all patients in the edema and infarction groups developed neurological
      symptoms. The rCBF in the edema group was significantly lower than that in the
      normal group, and significantly higher than that in the infarction group. The
      cerebral vascular reactivity (CVR) of the infarction group was significantly
      lower than that of the normal and edema groups. After treatment, the neurological
      signs disappeared in the edema group, but only partial improvement was seen in
      the infarction group. The rCBF also significantly increased in the normal and
      edema groups, but not in the infarction group. CONCLUSIONS: Quantitative rCBF
      measurement is useful for evaluating hemodynamic disturbance in dAVF with RLVD.
      The reduction of rCBF was strongly correlated with the severity of venous
      congestive encephalopathy, and loss of CVR is a reliable indicator of
      irreversible venous infarction caused by RLVD.

PMID- 25859805
TI  - Cerebrospinal fluid reconstitution via a perfusion-based cadaveric model:
      feasibility study demonstrating surgical simulation of neuroendoscopic
      procedures.
AB  - Cadaveric surgical simulation carries the advantage of realistic anatomy and
      haptic feedback but has been historically difficult to model for intraventricular
      approaches given the need for active flow of CSF. This feasibility study was
      designed to simulate intraventricular neuroendoscopic approaches and techniques
      by reconstituting natural CSF flow in a cadaveric model. In 10 fresh human
      cadavers, a simple cervical laminectomy and dural opening were made, and a 12
      gauge arterial catheter was introduced. Saline was continuously perfused at
      physiological CSF pressures to reconstitute the subarachnoid space and
      ventricles. A neuroendoscope was subsequently inserted via a standard right
      frontal bur hole. In 8 of the 10 cadavers, adequate reconstitution and endoscopic
      access of the lateral and third ventricles were achieved. In 2 cadavers,
      ventricular access was not feasible, perhaps because of a small ventricle size
      and/or deteriorated tissue quality. In all 8 cadavers with successful CSF flow
      reconstitution and endoscopic access, identifying the foramen of Monro was
      possible, as was performing septum pellucidotomy and endoscopic third
      ventriculostomy. Furthermore, navigation of the cerebral aqueduct, fourth
      ventricle, prepontine cistern, and suprasellar cistern via the lamina terminalis
      was possible, providing a complementary educational paradigm for resident
      education that cannot typically be performed in live surgery. Surgical simulation
      plays a critical and increasingly prominent role in surgical education,
      particularly for techniques with steep learning curves including intraventricular
      neuroendoscopic procedures. This novel model provides feasible and realistic
      surgical simulation of neuroendoscopic intraventricular procedures and
      approaches. 

PMID- 25859804
TI  - Management and outcomes of pituitary apoplexy.
AB  - OBJECT: This study was undertaken to analyze the predisposing factors, clinical
      presentation, therapeutic management, and clinical recovery in patients with
      pituitary apoplexy, with an emphasis on the long-term visual, endocrine, and
      functional outcomes. METHODS: The authors performed a retrospective analysis of
      consecutive cases involving patients treated at Mayo Clinic between 1992 and
      2013. Patients were included in the study only if they had 1) abrupt onset of
      severe headache or visual disturbance in the presence of a pituitary adenoma and
      2) radiological or surgical confirmation of a pituitary mass. The primary
      endpoints of analysis were the visual (ocular motility, visual fields, and visual
      acuity), endocrine, and functional outcomes (using the modified Rankin Scale).
      RESULTS: Eighty-seven patients were identified (57 males and 30 females, mean age
      50.9 years, range 15-91 years). Twenty-two patients (25.3%) had a known pituitary
      adenoma. Hypertension was the most common associated factor (39%). Headache was
      the most frequent presenting symptom (89.7%), followed by visual abnormalities
      (47.1%). Cranial nerve palsies were present in 39% and visual field defects in
      34.1%. MRI detected hemorrhage in 89% patients, as compared with 42% detected by
      CT scan. Sixty-one patients (70.1%) underwent surgery during acute
      hospitalization (median time from apoplexy 5 days, IQR 3-10 days), 8 (9.2%) had
      delayed surgery, and 18 (20.7%) were treated conservatively. Histopathological
      examination revealed adenoma with pure necrosis in 18 (30%), pure hemorrhage in 4
      (6.7%), and both in 6 (10%) patients. Four patients died during hospitalization.
      The average duration of follow-up was 44.2 +/- 43.8 months. All survivors were
      independent and had complete resolution or substantial improvement in eye
      movements and visual fields at the last follow-up. Many patients needed long-term
      hormonal replacement with levothyroxine (62.7%) and cortisol (60%). Daily
      desmopressin was needed in 23% of all surgical patients at 3 months (versus none
      of the medically treated) and this requirement decreased slightly over time.
      Regrowth of pituitary adenoma was seen in 7 patients (8.6%). There were no
      statistically significant differences in any of the outcome measures across the
      treatment groups. CONCLUSIONS: The outcome of most patients with pituitary
      apoplexy is excellent. Selected patients can be managed conservatively, and
      patients with severe neuro-ophthalmological deficits treated with early surgery
      can achieve an excellent recovery.

PMID- 25859806
TI  - Microsurgical anatomy of the inferior limiting insular sulcus and the temporal
      stem.
AB  - OBJECT: The purpose of this study was to describe the location of each white
      matter pathway in the area between the inferior limiting insular sulcus (ILS) and
      temporal horn that may be crossed in approaches through the temporal stem to the
      medial temporal lobe. METHODS: The fiber tracts in 14 adult cadaveric cerebral
      hemispheres were examined using the Klingler technique. The fiber dissections
      were completed in a stepwise manner, identifying each white matter pathway in
      different planes and describing its position in relation to the anterior end of
      the ILS. RESULTS: The short-association fibers from the extreme capsule, which
      continue toward the operculae, are the most superficial subcortical layer deep to
      the ILS. The external capsule fibers are found deeper at an intermediate layer
      and are formed by the uncinate fasciculus, inferior frontooccipital fasciculus,
      and claustrocortical fibers in a sequential anteroposterior disposition. The
      anterior commissure forms the next deeper layer, and the optic radiations in the
      sublenticular part of the internal capsule represent the deepest layer. The
      uncinate fasciculus is found deep to the anterior third of the ILS, whereas the
      inferior frontooccipital fasciculus and optic radiations are found superficial
      and deep, respectively, at the posterior two-thirds of this length. CONCLUSIONS:
      The authors' findings suggest that in the transsylvian approach, a 6-mm incision
      beginning just posterior to the limen insula through the ILS will cross the
      uncinate fasciculus but not the inferior frontooccipital fasciculus or optic
      radiations, but that longer incisions carry a risk to language and visual
      functions.

PMID- 25859807
TI  - Survival in patients treated for anaplastic meningioma.
AB  - OBJECT: While most meningiomas are benign, 1%-3% display anaplastic features,
      with little current understanding regarding the molecular mechanisms underlying
      their formation. In a large single-center cohort, the authors tested the
      hypothesis that two distinct subtypes of anaplastic meningiomas, those that arise
      de novo and those that progress from lower grade tumors, exist and exhibit
      different clinical behavior. METHODS: Pathology reports and clinical data of 37
      patients treated between 1999 and 2012 for anaplastic meningioma at Memorial
      Sloan-Kettering Cancer Center (MSKCC) were retrospectively reviewed. Patients
      were divided into those whose tumors arose de novo and those whose tumors
      progressed from previously documented benign or atypical meningiomas. RESULTS:
      Overall, the median age at diagnosis was 59 years and 57% of patients were
      female. Most patients (38%) underwent 2 craniotomies (range 1-5 surgeries) aimed
      at gross-total resection (GTR; 59%), which afforded better survival when compared
      with subtotal resection according to Kaplan-Meier estimates (median overall
      survival [OS] 3.2 vs 1.3 years, respectively; p = 0.04, log-rank test). Twenty
      three patients (62%) presented with apparently de novo anaplastic meningiomas.
      Compared with patients whose tumors had progressed from a lower grade, those
      patients with de novo tumors were significantly more likely to be female (70% vs
      36%, respectively; p = 0.04), experience better survival (median OS 3.0 vs 2.4
      years, respectively; p = 0.03, log-rank test), and harbor cerebral hemispheric as
      opposed to skull base tumors (91% vs 43%, respectively; p = 0.002). CONCLUSIONS:
      Based on this single-center experience at MSKCC, anaplastic meningiomas, similar
      to glial tumors, can arise de novo or progress from lower grade tumors. These
      tumor groups appear to have distinct clinical behavior. De novo tumors may well
      be molecularly distinct, which is under further investigation. Aggressive GTR
      appears to confer an OS advantage in patients with anaplastic meningioma, and
      this is likely independent of tumor progression status. Similarly, those patients
      with de novo tumors experience a survival advantage likely independent of extent
      of resection.

PMID- 25859809
TI  - Letter to the Editor: Malignant meningiomas.

PMID- 25859808
TI  - Assessment of third ventriculostomy patency with the 3D-SPACE technique: a
      preliminary multicenter research study.
AB  - OBJECT: The goal of this study was to determine the value of the 3D sampling
      perfection with application-optimized contrasts using different flip-angle
      evolutions (3D-SPACE) technique in the evaluation of endoscopic third
      ventriculostomy (ETV) patency. METHODS: Twenty-six patients with ETV were
      examined using 3-T MRI units. Sagittal-plane 3D-SPACE with variant flip-angle
      mode, 3D T1-weighted (T1W), and 3D heavily T2-weighted (T2W) images were obtained
      with isotropic voxel sizes. Also, sagittal-axial plane phase-contrast cine (PC)
      MR images were obtained. The following findings were evaluated: diameters of
      stoma and third ventricle, flow-void sign on 3D-SPACE and PC-MR images, integrity
      of the third ventricle on heavily T2W images, and quantitative PC-MRI parameters
      of the stoma. Obtained sequences were evaluated singly, in combination with one
      another, and all together. RESULTS: The mean area, flow, and velocity values
      measured at the level of stoma in patients with patent stoma were significantly
      higher than those measured in patients with closed stoma (p < 0.05). There was
      significant correlation among PC-MRI, 3D-SPACE, and 3D heavily T2W techniques
      regarding assessment of ETV patency (p < 0.001). The 3D-SPACE technique provided
      the lowest rate of ambiguous results. CONCLUSIONS: The 3D-SPACE technique seems
      to be the most efficient one for determination of ETV patency. The authors
      suggest the use of 3D-SPACE as a stand-alone first-line sequence in addition to
      routine brain MRI protocols in assessing patients with ETV, thereby decreasing
      scan time and reserving the use of a combination of additional sequences such as
      PC-MRI and 3D heavily T2W images in suspicious or complex cases.

PMID- 25859810
TI  - Risks associated with preoperative anemia and perioperative blood transfusion in
      open surgery for intracranial aneurysms.
AB  - OBJECT: Preoperative anemia may be treated with a blood transfusion. Both are
      associated with adverse outcomes in various surgical procedures, but this has not
      been clearly elucidated in surgery for cerebral aneurysms. In this study the
      authors assessed the association of preoperative anemia and perioperative blood
      transfusion, separately, on 30-day morbidity and mortality in patients undergoing
      open surgery for ruptured and unruptured intracranial aneurysms. METHODS: The
      authors identified 668 cases (including 400 unruptured and 268 unruptured
      intracranial aneurysms) of open surgery for treatment of intracranial aneurysms
      in the 2006-2012 National Surgical Quality Improvement Program, a validated and
      reproducible prospective clinical database. Anemia was defined as a hematocrit
      level less than 39% in males and less than 36% in females. Perioperative
      transfusion was defined as at least 1 unit of packed or whole red blood cells
      given at any point between the start of surgery to 72 hours postoperatively. The
      authors separately compared surgical outcome between patients with (n = 198)
      versus without (n = 470) anemia, and those who underwent (n = 78) versus those
      who did not receive (n = 521) a transfusion, using a 1:1 match on propensity
      score. RESULTS: In the matched cohorts, all observed covariates were comparable
      between anemic (n = 147) versus nonanemic (n = 147) and between transfused (n =
      67) versus nontransfused patients (n = 67). Anemia was independently associated
      with prolonged hospital length of stay (LOS; odds ratio [OR] 2.5, 95% confidence
      interval [CI] 1.4-4.5), perioperative complications (OR 1.9, 95% CI 1.1-3.1), and
      return to the operating room (OR 2.1, 95% CI 1.1-4.5). Transfusion was also
      independently associated with perioperative complications (OR 2.4, 95% CI 1.1
      5.3). CONCLUSIONS: Preoperative anemia and transfusion are each independent risk
      factors for perioperative complications in patients undergoing surgery for
      cerebral aneurysms. Perioperative anemia is also associated with prolonged
      hospital LOS and 30-day return to the operating room.

PMID- 25859811
TI  - Predictability of the future development of aggressive behavior of cranial dural
      arteriovenous fistulas based on decision tree analysis.
AB  - OBJECT: The severity of clinical signs and symptoms of cranial dural
      arteriovenous fistulas (DAVFs) are well correlated with their pattern of venous
      drainage. Although the presence of cortical venous drainage can be considered a
      potential predictor of aggressive DAVF behaviors, such as intracranial hemorrhage
      or progressive neurological deficits due to venous congestion, accurate
      statistical analyses are currently not available. Using a decision tree data
      mining method, the authors aimed at clarifying the predictability of the future
      development of aggressive behaviors of DAVF and at identifying the main causative
      factors. METHODS: Of 266 DAVF patients, 89 were eligible for analysis. Under
      observational management, 51 patients presented with intracranial
      hemorrhage/infarction during the follow-up period. RESULTS: The authors created a
      decision tree able to assess the risk for the development of aggressive DAVF
      behavior. Evaluated by 10-fold cross-validation, the decision tree's accuracy,
      sensitivity, and specificity were 85.28%, 88.33%, and 80.83%, respectively. The
      tree shows that the main factor in symptomatic patients was the presence of
      cortical venous drainage. In its absence, the lesion location determined the risk
      of a DAVF developing aggressive behavior. CONCLUSIONS: Decision tree analysis
      accurately predicts the future development of aggressive DAVF behavior.

PMID- 25859812
TI  - Gamma Knife radiosurgery for posterior fossa meningiomas: a multicenter study.
AB  - OBJECT: Posterior fossa meningiomas represent a common yet challenging clinical
      entity. They are often associated with neurovascular structures and adjacent to
      the brainstem. Resection can be undertaken for posterior fossa meningiomas, but
      residual or recurrent tumor is frequent. Stereotactic radiosurgery (SRS) has been
      used to treat meningiomas, and this study evaluates the outcome of this approach
      for those located in the posterior fossa. METHODS: At 7 medical centers
      participating in the North American Gamma Knife Consortium, 675 patients
      undergoing SRS for a posterior fossa meningioma were identified, and clinical and
      radiological data were obtained for these cases. Females outnumbered males at a
      ratio of 3.8 to 1, and the median patient age was 57.6 years (range 12-89 years).
      Prior resection was performed in 43.3% of the patient sample. The mean tumor
      volume was 6.5 cm(3), and a median margin dose of 13.6 Gy (range 8-40 Gy) was
      delivered to the tumor. RESULTS: At a mean follow-up of 60.1 months, tumor
      control was achieved in 91.2% of cases. Actuarial tumor control was 95%, 92%, and
      81% at 3, 5, and 10 years after radiosurgery. Factors predictive of tumor
      progression included age greater than 65 years (hazard ratio [HR] 2.36, 95% CI
      1.30-4.29, p = 0.005), prior history of radiotherapy (HR 5.19, 95% CI 1.69-15.94,
      p = 0.004), and increasing tumor volume (HR 1.05, 95% CI 1.01-1.08, p = 0.005).
      Clinical stability or improvement was achieved in 92.3% of patients. Increasing
      tumor volume (odds ratio [OR] 1.06, 95% CI 1.01-1.10, p = 0.009) and clival,
      petrous, or cerebellopontine angle location as compared with petroclival,
      tentorial, and foramen magnum location (OR 1.95, 95% CI 1.05-3.65, p = 0.036)
      were predictive of neurological decline after radiosurgery. After radiosurgery,
      ventriculoperitoneal shunt placement, resection, and radiation therapy were
      performed in 1.6%, 3.6%, and 1.5%, respectively. CONCLUSIONS: Stereotactic
      radiosurgery affords a high rate of tumor control and neurological preservation
      for patients with posterior fossa meningiomas. Those with a smaller tumor volume
      and no prior radiation therapy were more likely to have a favorable response
      after radiosurgery. Rarely, additional procedures may be required for
      hydrocephalus or tumor progression.

PMID- 25859813
TI  - Letter to the Editor: Minimally invasive technique for epilepsy surgery.

PMID- 25859815
TI  - Formation of a Stable Complex, RuCl2(S2CPPh3)(PPh3)2, Containing an Unstable
      Zwitterion from the Reaction of RuCl2(PPh3)3 with Carbon Disulfide.
AB  - New insight into the complexity of the reaction of the prominent catalyst
      RuCl2(PPh3)3 with carbon disulfide has been obtained from a combination of X-ray
      diffraction and (31)P NMR studies. The red-violet compound originally formulated
      as a cationic pi-CS2 complex, [RuCl(pi-CS2)(PPh3)3]Cl, has been identified as a
      neutral molecule, RuCl2(S2CPPh3)(PPh3)2, which contains the unstable zwitterion
      S2CPPh3. In the absence of RuCl2(PPh3)3, there is no sign of a reaction between
      triphenylphosphine and carbon disulfide, although more basic trialkylphosphines
      form red adducts, S2CPR3. Despite the presence of an unstable ligand,
      RuCl2(S2CPPh3)(PPh3)2 is remarkably stable. It survives melting at 173-174 
      degrees C intact, is stable to air, and undergoes reversible electrochemical
      oxidation to form a monocation. When the reaction of RuCl2(PPh3)3 with carbon
      disulfide is conducted in the presence of methanol, crystals of orange
      [RuCl(S2CPPh3)(CS)(PPh3)2]Cl.2MeOH and yellow RuCl2(CS)(MeOH)(PPh3)2 also form.
      (31)P NMR studies indicate that the unsymmetrical dinuclear complex
      (SC)(Ph3P)2Ru(MU-Cl)3Ru(PPh3)2Cl is the initial product of the reaction of
      RuCl2(PPh3)3 with carbon disulfide. A path connecting the isolated products is
      presented. 

PMID- 25859814
TI  - Letter to the Editor: Endoscopic transnasal transcribriform approach.

PMID- 25859816
TI  - New views on the reaction of primary amine and aldehyde from DFT study.
AB  - A general theoretical investigation on the reaction of primary amine with
      aldehyde was carried out by density functional theory. The calculation systems
      involve three kinds of primary amines (methylamine, vinylamine, and phenylamine)
      and three kinds of aldehydes (formaldehyde, acetaldehyde, and acrylaldehyde). The
      steric and electronic inductive effects on the reaction mechanism were studied.
      Results reveal that the nucleophilic attack of primary amine on aldehyde under
      neutral conditions leads to carbinolamines, rather than Schiff bases. The
      nucleophilic attack on the protonated aldehyde produces the protonated Schiff
      base. The steric hindrance of the aldehyde slows down the nucleophilic attack but
      allows enough time to abstract a H; consequently, the formation of the protonated
      Schiff base is preferred. During the carbinolamine protonation, the H(+)
      preferably locates on the amine nitrogen and then is abstracted by the hydroxyl
      oxygen over an energy barrier, leaving protonated Schiff base after timely water
      liberation. The formation of a prereaction potential energy well obviously
      softens the steric and electronic inductive effects on the active barrier for
      different reactants. 

PMID- 25859817
TI  - BF3-Mediated cis-Selective Cycloaddition of O-Silyloxime with Alkenes.
AB  - A C-amide-substituted O-silylated oxime, (E)-(tert
      butyldimethylsiloxyimino)acetic acid N,N-dimethylamide (8b), on treatment with
      2.2 equiv of BF3.OEt2, in situ generated boracyclic nitrone-type intermediate
      BF3.14, which underwent cycloaddition with alkenes to give 3,5-cis-isoxazolidines
      as the major products. The mechanism was strongly supported by isolation of the
      reaction intermediate 14 that was characterized by X-ray diffraction and its
      further reaction. This cycloaddition was successfully applied to the synthesis of
      syn-HPA-12 known as an inhibitor of CERT that mediates the transport of ceramide.

PMID- 25859818
TI  - Influence of the local atom configuration on a hexagonal skyrmion lattice.
AB  - Spin-resolved scanning tunneling microscopy is used to reveal a commensurate
      hexagonal nanoskyrmion lattice in the hcp stacked Fe monolayer on Ir(111). The
      exact nature of the spin configuration is due to magnetic interactions between
      the Fe atoms and the Ir substrate, either originating from polarization effects,
      or due to a three-site hopping mechanism of the Dzyaloshinsky-Moriya interaction
      leading to a canting of the Dzyaloshinsky-Moriya vector with respect to the
      interface. 

PMID- 25859819
TI  - Identifying overlapping mutated driver pathways by constructing gene networks in
      cancer.
AB  - BACKGROUND: Large-scale cancer genomic projects are providing lots of data on
      genomic, epigenomic and gene expression aberrations in many cancer types. One key
      challenge is to detect functional driver pathways and to filter out nonfunctional
      passenger genes in cancer genomics. Vandin et al. introduced the Maximum Weight
      Sub-matrix Problem to find driver pathways and showed that it is an NP-hard
      problem. METHODS: To find a better solution and solve the problem more
      efficiently, we present a network-based method (NBM) to detect overlapping driver
      pathways automatically. This algorithm can directly find driver pathways or gene
      sets de novo from somatic mutation data utilizing two combinatorial properties,
      high coverage and high exclusivity, without any prior information. We firstly
      construct gene networks based on the approximate exclusivity between each pair of
      genes using somatic mutation data from many cancer patients. Secondly, we present
      a new greedy strategy to add or remove genes for obtaining overlapping gene sets
      with driver mutations according to the properties of high exclusivity and high
      coverage. RESULTS: To assess the efficiency of the proposed NBM, we apply the
      method on simulated data and compare results obtained from the NBM, RME, Dendrix
      and Multi-Dendrix. NBM obtains optimal results in less than nine seconds on a
      conventional computer and the time complexity is much less than the three other
      methods. To further verify the performance of NBM, we apply the method to analyze
      somatic mutation data from five real biological data sets such as the mutation
      profiles of 90 glioblastoma tumor samples and 163 lung carcinoma samples. NBM
      detects groups of genes which overlap with known pathways, including P53, RB and
      RTK/RAS/PI(3)K signaling pathways. New gene sets with p-value less than 1e-3 are
      found from the somatic mutation data. CONCLUSIONS: NBM can detect more
      biologically relevant gene sets. Results show that NBM outperforms other
      algorithms for detecting driver pathways or gene sets. Further research will be
      conducted with the use of novel machine learning techniques.

PMID- 25859820
TI  - An exploratory analysis of the regionalization policy for the recruitment of
      health workers in Burkina Faso.
AB  - BACKGROUND: Health personnel retention in remote areas is a key health systems
      issue wordwide. To deal with this issue, since 2002 the government of Burkina
      Faso has implemented a staff retention policy, the regionalized health personnel
      recruitment policy, aimed at front-line workers such as nurses, midwives, and
      birth attendants. This study aimed to describe the policy's development,
      formulation, and implementation process for the regionalization of health worker
      recruitment in Burkina Faso. METHODS: We conducted a qualitative study. The unit
      of analysis is a single case study with several levels of analysis. This study
      was conducted in three remote areas in Burkina Faso for the implementation
      portion, and at the central level for the development portion. Indepth interviews
      were conducted with Ministry of Health officials in charge of human resources,
      regional directors, regional human resource managers, district chief medical
      officers, and health workers at primary health centres. In total, 46 in depth
      interviews were conducted (February 3 - March 16, 2011). RESULTS:  DEVELOPMENT:
      The idea for this policy emerged after finding a highly uneven distribution of
      health personnel across urban and rural areas, the availability of a large number
      of health officers in the labour market, and the opportunity given to the
      Ministry of Health by the government to recruit personnel through a specific
      budget allocation. FORMULATION: The formulation consisted of a call for job
      applications from the Ministry of Health, which indicates the number of available
      posts by region.The respondents interviewed unanimously acknowledged the lack of
      documents governing the status of this new personnel category. IMPLEMENTATION:
      During the initial years of implementation (2002-2003), this policy was limited
      to recruiting health workers for the regions with no possibility of transfer. The
      possibility of job-for-job exchange was then approved for a certain time, then
      cancelled. Starting in 2005, a departure condition was added. Now, regionalized
      health workers can leave the regions after undergoing a competitive selection
      process. CONCLUSION: The policy was characterized by the absence of written
      directives and by targeting only one category of personnel. Moreover, there was
      no associated incentive-financial or otherwise-which poses the question of long
      term viability.

PMID- 25859821
TI  - Retrospective Study on the Analgesic Activity of a Topical (TT-CTAC) Cream in
      Patients With Diabetic Neuropathy and Other Chronic Pain Conditions.
AB  - Treatment of chronic pain in diabetic neuropathy or neuropathic pain of other
      origins is challenging. Compounded topical formulations have evolved as potential
      treatment options. The objective of this retrospective study was to evaluate the
      efficacy of a compounded topical cream (Transdermal Therapeutics). Two versions
      of TT-CTAC cream were evaluated: cream 6B and cream 7B. Both creams contain
      ketamine (10%), baclofen (2%), gabapentin (6%), amitriptyline (4%), bupivacaine
      (2%), and clonidine (0.2%). Additionally, one cream (7B) contains nifedipine
      (2%). The primary efficacy outcome was the change in numeric pain intensity score
      from pretreatment to posttreatment. Secondary outcomes were qualitative grading
      (excellent, good, poor, or no effect), reduction in oral medication, and avoiding
      referral to a pain specialist. Information on 283 patients was evaluated, 205
      received the 7B and 78 received 6B creams. The pain score decreased by 2.4 +/-
      2.4 (35%) with the 6B cream (from 7.8 +/- 1.6 to 5.4 +/- 2.0, P < 0.001) and by
      3.0 +/- 2.4 (40%) with the 7B cream (from 7.5 +/- 1.7 to 4.5 +/- 2.2, P < 0.001).
      Excellent or good effects were reported in 82% of the patients in the 6B and in
      70% in the 7B groups. Reduction in oral pain medication was seen in 35% of the
      patients in the 7B and in 20% in the 6B groups. In the opinion of the treating
      physicians, the cream therapy caused the avoidance of a pain specialist referral
      in 53% of the patients in the 6B and in 39% in the 7B groups. The creams were
      equally effective in diabetic neuropathy, neuropathic pain, or other chronic pain
      states. We conclude that both creams provided excellent pain relief in the
      majority of the patients studied and may be a useful modality for pain therapy.

PMID- 25859823
TI  - Acetaminophen Adducts Detected in Serum of Pediatric Patients With Acute Liver
      Failure.
AB  - OBJECTIVES: Previous studies in patients with acute liver failure identified
      acetaminophen (APAP) protein adducts in the serum of 12% and 19% of children and
      adults, respectively, with acute liver failure of indeterminate etiology. This
      article details the testing of APAP adducts in a subset (n = 393) of patients
      with varied diagnoses in the Pediatric Acute Liver Failure Study Group (PALFSG).
      METHODS: Serum samples were available from 393 participants included in the
      PALFSG registry. Adduct measurement was performed using validated methods.
      Participants were grouped by diagnostic category as known APAP overdose, known
      other diagnosis, and indeterminate etiology. Demographic and clinical
      characteristics and participant outcomes were compared by adduct status (positive
      or negative) within each group. RESULTS: APAP adduct testing was positive in 86%
      of participants with known APAP overdose, 6% with other known diagnoses, and 11%
      with an indeterminate cause of liver failure. Adduct-positive participants were
      noted to have marked elevation of serum alanine aminotransferase and aspartate
      aminotransferase coupled with total serum bilirubin that was significantly lower
      than adduct-negative patients. In the indeterminate group, adduct-positive
      patients had different outcomes than adduct-negative patients (P = 0.03);
      spontaneous survival was 16 of 21 (76%) in adduct-positive patients versus 75 of
      169 (44%) in adduct-negative patients. Prognosis did not vary by adduct status in
      patients with known diagnoses. CONCLUSIONS: Furthermore, study is needed to
      understand the relation of APAP exposure, as determined by the presence of APAP
      adducts, to the clinical phenotype and outcomes of children with acute liver
      failure.

PMID- 25859824
TI  - Gastrointestinal Infantile Hemangioma: Presentation and Management.
AB  - OBJECTIVES: The aim of the present study was to document the clinical
      presentation, diagnostic studies, and therapy of gastrointestinal infantile
      hemangiomas. METHODS: This is a retrospective analysis of children with
      gastrointestinal hemangiomas culled from our Vascular Anomalies Center database.
      We detailed the location of visceral and cutaneous tumors, as well as radiologic
      and procedural methods used for diagnosis and treatment. RESULTS: A total of 9 of
      the 16 children (14 girls and 2 boys) with hollow visceral hemangiomas also had
      cutaneous lesions. The most common extravisceral sites were regional facial
      lesions (n = 6), multifocal lesions (n = 2), and a solitary chest lesion (n = 1).
      Presenting symptoms were melena and hematochezia in the first 4 months of life (n
      = 14); several infants required multiple blood transfusions. The most frequent
      locations were small bowel and mesentery. One-half of the patients (n = 8) were
      diagnosed by laparotomy; the majority (n = 12) had suspicious radiologic
      findings. Corticosteroid and/or propranolol were the most common therapies.
      CONCLUSIONS: Melena and hematochezia, sometimes with profound anemia, in the
      first 4 months of life, suggest the possibility of intestinal infantile
      hemangioma even in the absence of cutaneous tumor. Intestinal bleeding,
      particularly in association with a regional facial lesion, should initiate
      workup: ultrasonography, computed tomography, and magnetic resonance imaging
      display diagnostic features. First-line treatment is medical management; bowel
      resection may be necessary, particularly for perforation.

PMID- 25859825
TI  - Emergency Department Visits Related to Inflammatory Bowel Disease: Results From
      Nationwide Emergency Department Sample.
AB  - We analyzed a national US database to study the presentation of children with
      inflammatory bowel disease (IBD) to the emergency department (ED). Our results
      indicate that from 2006 to 2010, there was a significant increase in the number
      of ED visits related to children with IBD accompanied by a contemporaneous
      decline in the rate of hospitalization that followed these ED visits. Earlier
      published results have highlighted an increased overall rate of hospitalizations
      in the United States related to children with IBD. In this context, our results
      support the evidence for an increased prevalence of pediatric IBD in the United
      States in recent years.

PMID- 25859826
TI  - Primum Non Nocere.

PMID- 25859827
TI  - Association of the intercellular adhesion molecule-1 (ICAM-1) gene polymorphisms
      with endometriosis: a systematic review and meta-analysis.
AB  - BACKGROUND: Reported associations of the G241R and K469E polymorphisms of the
      intercellular adhesion molecule-1 gene (ICAM-1) gene with endometriosis have
      differed in magnitude. MATERIALS AND METHODS: In a meta-analysis of six published
      case-control studies (from five articles), we estimated risk [odds ratio (OR) 95
      % confidence intervals (CI)] of associations with these polymorphisms using the
      Review Manager 5.3 software. RESULTS: Based on 1213 cases and 1103 controls,
      overall analysis showed significant increased risk in the homozygous (OR 2.83, 95
      % CI 0.99-8.10, p = 0.05), dominant (OR 1.86, 95 % CI 1.00-3.46, p = 0.05) and
      codominant (OR 2.15, 95 % CI 1.06-4.35, p = 0.03) models. Confined to the studies
      in Hardy-Weinberg Equilibrium erased the significance (OR 1.59-2.59, 95 % CI 0.81
      8.22, p = 0.10-0.15). Asian effects were variable (OR 0.93-1.09, p = 0.50-0.57),
      but Caucasian effects were not (OR 4.09-13.60, p < 0.0001). Independent data for
      the late stages of endometriosis suggest protection of the ICAM-1 K469E
      polymorphism among the Asians (OR 0.91-0.95, p = 0.35-0.71). These effects were
      weak but non-heterogeneous (P heterogeneity = 0.17-0.57, I (2) = 0-40 %).
      CONCLUSION: In summary, strengths of the overall effects were consistency,
      significance and robustness but limited by their high heterogeneity. These
      strengths and limitations were also observed in the Caucasian subgroup which when
      tested for interaction against the contrasting Asian effects, highlighted
      Caucasian susceptibility (p = 0.004-0.01). The findings are an interplay of
      strengths and limitations, which warrant awareness of their interpretation as
      susceptibility markers for this disorder.

PMID- 25859828
TI  - Screening occult anal sphincter injuries in primigravid women after vaginal
      delivery with transperineal use of vaginal probe: a prospective, randomized
      controlled trial.
AB  - PURPOSE: Here we aimed to evaluate the incidence of obstetric anal sphincter
      injuries in spontaneous primigravid deliveries with mediolateral episiotomy
      beyond 36 gestational weeks. METHODS: We performed a prospective, randomized
      controlled study including 201 primigravid women that delivered vaginally. Anal
      sphincter anatomy and integrity was evaluated before hospital discharge in all
      cases with transvaginal sonography (5-9 MHz) (Siemens Sonoline G50 and Voluson
      730 Expert). The vaginal ultrasound probe is placed in the fourchette of the
      vaginal introitus to obtain the transverse section of the anal sphincter.
      RESULTS: In the cases with sphincter defect, mean gestational week and second
      stage of labor were prolonged significantly (p = 0.039 and p < 0.0001,
      respectively). The mean perineal body distance in cases with sphincter injury, as
      detected by sonography, 2.18 +/- 0.33 cm, is compared to 2.31 +/- 2.43 cm in
      cases without injury. There was a significant difference between the two groups
      (p = 0.0142). Shoulder dystocia was significantly higher in cases with sphincter
      injury, compared to cases without injury (p = 0.011). No clinical findings were
      reported in 11.5 % of cases (Sonography findings 1A?, 1B?) and 3.5 % of cases had
      clinical and sonographic findings (Sonography findings 2A?, 2B?). "Occult tears"
      were considered as those cases not detected clinically, but detected by
      sonography (11.5 % of all cases). Two months after examination, a moderate
      incontinence (Wexner continence scale) was found in 71.5 % of cases with overt
      sphincter tear, which was significantly different to the non-overt sphincter tear
      group. Multiple logistic regression analyses for sphincter injuries identified
      prolonged second stage of labor and shoulder dystocia as two independent risk
      factors. CONCLUSION: Here, we found that only a portion of anal sphincter
      injuries can be detected after physical examination, with many of cases of
      "occult tears" escaping notice. These cases of occult anal sphincter injury are
      detectable by sonography with transperineal use of a vaginal probe. Based on
      these findings, we propose that this technique is convenient for obstetric,
      gynecologic and proctologic evaluation of sphincter anatomy.

PMID- 25859829
TI  - Soft tissue sarcoma and radiation therapy advances, impact on toxicity.
AB  - OPINION STATEMENT: Since adjuvant radiotherapy was introduced in the 1970s for
      soft tissue sarcoma (STS), sequential clinical trials characterized the
      toxicities induced by radiotherapy when given post-operatively and pre
      operatively. Gradual technological advancements led to more precise radiotherapy
      delivery through intensity-modulated radiation therapy (IMRT) and more accurate
      targeting through image-guided radiotherapy (IGRT) to minimize normal tissues
      from high-dose irradiation. These improvements ultimately reduced the long-term
      toxicities from radiotherapy. Due to the rarity and complexity of the disease,
      patients with STS should be treated at institutes where multidisciplinary
      discussion and care can be provided. Patients with STS should ideally be offered
      the choice of participating in clinical trials. International phase III trials
      are ongoing through COG-NRG Oncology (Pazopanib Neoadjuvant Trial in Non
      Rhabdomyosarcoma Soft Tissue Sarcomas (PAZNTIS)) to define the role of
      radiotherapy in combination with pazopanib in the clinical care of extremity STS
      and through EORTC (STRASS) to define the role of pre-operative radiotherapy in
      the treatment of retroperitoneal STS. Outside of clinical trials, extremity STS
      should be treated at centers of expertise where high-quality IMRT-IGRT is
      administered to lessen acute and long-term toxicities. In patients with extremity
      STS, pre-operative IMRT-IGRT is preferred as better target delineation and image
      guidance can be achieved. While acute wound complication remains a concern,
      patients treated using pre-operative IMRT-IGRT are largely spared of severe
      chronic irreversible radiation-related side effects such as bone fracture,
      fibrosis, edema, and joint stiffness that alter limb functions. For STS
      originating from the retroperitoneum, if radiotherapy is recommended following
      multidisciplinary case discussion, pre-operative radiotherapy is preferred over
      post-operative radiotherapy. Post-operatively, normal radiosensitive organs fill
      the surgical cavity, which is the targeted volume of radiotherapy; hence, post
      operative radiotherapy for retroperitoneal STS is associated with severe to fatal
      toxicities. Pre-operative radiotherapy has a more favorable toxicity profile as
      the retroperitoneal STS displaces, and thus spares, normal structures and organs
      from the high-dose irradiation volume.

PMID- 25859830
TI  - Immunotherapy in upper GI malignancies.
AB  - OPINION STATEMENT: A comprehensive analysis of the interactions that can occur
      amongst three complex systems-the tumor cell, tissue microenvironment, and the
      immune response, is required if we are to realize the potential of
      immunotherapeutics in gastroesophageal cancer. For many years, epithelial cancers
      were believed to originate due to the transformation of tissue stem cells.
      Recently however, it has suggested that bone marrow-derived cells (BMDCs), which
      are frequently recruited to sites of tissue injury and inflammation, might also
      represent a potential source of malignancy. The link between infection, chronic
      inflammation, and cancer has long been recognized in gastric cancer with its
      close association with Helicobacter pylori as a class I carcinogen. The long-term
      consequences of recruiting pluripotent cells to areas of chronic inflammation
      which can result in altered cell signaling and differentiation needs to be
      defined, but this work provides a fascinating insight into the pivotal role
      played by the immune system in the development of upper GI tumors. Here, we
      discuss many of the immunotherapeutic strategies that have been assessed in
      gastroesophageal cancer in the last two decades. At the time of writing, the use
      of checkpoint inhibitors represents the most exciting approach and displays the
      greatest potential for widespread adoption in the clinic. Preliminary data
      suggest that programmed death ligand-1 (PD-L1) expression ranges from
      approximately 18 to 42% in gastroesophageal cancer. Phase II and phase III
      clinical trials involving either single agent PD-1/PD-L1 inhibition or combined
      with CTLA-4 inhibitors are currently enrolling, and it is expected that
      checkpoint inhibition will become a new standard of care in the management of
      advanced disease in the near future.

PMID- 25859831
TI  - Dose-dense approaches to ovarian cancer treatment.
AB  - OPINION STATEMENT: Currently, paclitaxel and carboplatin are administered every 3
      weeks as the standard agents for the first-line treatment of advanced ovarian
      cancer. The concept of "dose-dense therapy" is based on the Norton-Simon
      hypothesis that a shorter interval between the doses of cytotoxic agents is more
      effective in reducing tumor burden than dose escalation. The results of phase III
      clinical trials demonstrating the superiority of weekly paclitaxel
      administration, compared with a 3-week schedule in breast cancer in both the
      metastatic and adjuvant settings support the hypothesis. The Japanese Gynecologic
      Oncology Group reported the results from a phase III study comparing the
      conventional paclitaxel and carboplatin every 3-week administration vs dose-dense
      weekly administration of paclitaxel combined with the every 3-week administration
      of carboplatin in advanced epithelial ovarian cancer, Fallopian tube, or primary
      peritoneal cancer. The median progression-free survival (PFS), the primary
      endpoint of this study, was substantially improved in the dose-dense treatment
      group (28 vs 17.2 months, hazard ratio [HR]: 0.71, 95% CI: 0.58-0.88, P =
      0.0015), and the overall survival (OS) at 3 years was also higher in the dose
      dense treatment group (72 . 1%) than in the conventional treatment group (65.1%;
      HR 0.75, 0.57-0.98; P = 0 . 03). The long-term outcomes at a median follow-up
      period of 76.8 months were reported. The median PFS was significantly longer in
      the dose-dense regimen than in the conventional regimen (28.2 vs 17.5 months;
      hazard ratio [HR], 0.76; 95% CI, 0.62-0.91; P = 0.0037), and the median OS was
      100.5 months (95% CI 65.2-infinity) in the dose-dense regimen and 62.2 months
      (52.1-82.6) in the conventional regimen (HR, 0.79; 95% CI, 0.63-0.99; P = 0.039;
      log-rank test). Dose-dense treatment offers a potential new standard of care for
      first-line chemotherapy for patients with advanced epithelial ovarian cancer.
      Ongoing studies will clarify the best dose, schedule, and route of
      administration.

PMID- 25859833
TI  - Midbrain morphology reflects extent of brain damage in Krabbe disease.
AB  - INTRODUCTION: To study the relationships between midbrain morphology, Loes score,
      gross motor function, and cognitive function in infantile Krabbe disease.
      METHODS: Magnetic resonance imaging (MRI) scans were evaluated by two
      neuroradiologists blinded to clinical status and neurodevelopmental function of
      children with early or late infantile Krabbe disease. A simplified qualitative 3
      point scoring system based on midbrain morphology on midsagittal MRI was used. A
      score of 0 represented normal convex morphology of the midbrain, a score of 1
      represented flattening of the midbrain, and a score of 3 represented concave
      morphology of the midbrain (hummingbird sign). Spearman correlations were
      estimated between this simplified MRI scoring system and the Loes score, gross
      motor score, and cognitive score. RESULTS: Forty-two MRIs of 27 subjects were
      reviewed. Analysis of the 42 scans showed normal midbrain morphology in 3 (7.1%)
      scans, midbrain flattening in 11 (26.2%) scans, and concave midbrain morphology
      (hummingbird sign) in 28 (66.7%) scans. Midbrain morphology scores were
      positively correlated with the Loes score (r = 0.81, p < 0.001) and negatively
      correlated with both gross motor and cognitive scores (r = -.84, p < 0.001; r = 
      0.87, p < 0.001, respectively). The inter-rater reliability for the midbrain
      morphology scale was kappa = .95 (95% CI: 0.86-1.0), and the inter-rater
      reliability for the Loes scale was kappa = .58 (95% CI: 0.42-0.73). CONCLUSIONS:
      Midbrain morphology scores of midsagittal MRI images correlates with cognition
      and gross motor function in children with Krabbe disease. This MRI scoring system
      represents a simple but reliable method to assess disease progression in patients
      with infantile Krabbe disease.

PMID- 25859834
TI  - Thrombectomy in patients with tandem stenoses.

PMID- 25859835
TI  - Pre-exposure to Cadmium or Zinc Alters the Heart Rate Response of the Crayfish
      Procambarus clarkii Towards Copper.
AB  - Exposure to sub-lethal concentrations of a pollutant induces, in some organisms,
      an acclimation process which increases their resistance to other substances
      (cross-acclimation). Understanding this phenomenon is important as a basis for a
      better comprehension of the effects of pollutants in ecosystems. In this paper we
      investigated whether the exposure to Cd or Zn is able to modify the heart rate
      response of the crayfish Procambarus clarkii to acute Cu stress. A first set of
      experiments provided the basis to understand heart rate changes induced by
      varying Cd or Zn concentrations. In a second set of experiments crayfish were
      acclimated for 96 h to control water, Cd or Zn enriched water, and then exposed
      to a 10 mg L(-1) Cu solution, known to induce bradycardia in this species.
      Bradycardia was suppressed in specimens previously exposed to Cd or Zn but not in
      those exposed to clean water, providing a clear evidence of a cross-acclimation
      in the heart rate response of P. clarkii.

PMID- 25859832
TI  - State-of-the-art MRI techniques in neuroradiology: principles, pitfalls, and
      clinical applications.
AB  - This article reviews the most relevant state-of-the-art magnetic resonance (MR)
      techniques, which are clinically available to investigate brain diseases. MR
      acquisition techniques addressed include notably diffusion imaging (diffusion
      weighted imaging (DWI), diffusion tensor imaging (DTI), and diffusion kurtosis
      imaging (DKI)) as well as perfusion imaging (dynamic susceptibility contrast
      (DSC), arterial spin labeling (ASL), and dynamic contrast enhanced (DCE)). The
      underlying models used to process these images are described, as well as the
      theoretic underpinnings of quantitative diffusion and perfusion MR imaging-based
      methods. The technical requirements and how they may help to understand,
      classify, or follow-up neurological pathologies are briefly summarized.
      Techniques, principles, advantages but also intrinsic limitations, typical
      artifacts, and alternative solutions developed to overcome them are discussed. In
      this article, we also review routinely available three-dimensional (3D)
      techniques in neuro MRI, including state-of-the-art and emerging angiography
      sequences, and briefly introduce more recently proposed 3D quantitative neuro
      anatomy sequences, and new technology, such as multi-slice and multi-transmit
      imaging. 

PMID- 25859836
TI  - Near-infrared noninvasive blood glucose prediction without using multivariate
      analyses: introduction of imaginary spectra due to scattering change in the skin.
AB  - A noninvasive measurement method is proposed and examined to continuously predict
      blood glucose contents using near-infrared diffuse reflection difference spectra
      measured at the skin tissue without using multivariate analyses. Using the
      modified Beer's law, the difference spectra are assumed to be synthesized from
      four major components in the human skin (water, protein, glucose, and fat) and a
      scattering equivalent component called baseline. As a result, one of the origins
      of the errors in blood glucose prediction using near-infrared is found to be the
      similarity of the shapes of the absorption spectrum between glucose and baseline.
      After separating the glucose contributions from the difference spectra at the
      characteristic wavelengths of baseline and fat, an imaginary component combining
      baseline and fat is introduced by considering that both the change in the fat
      contribution and the generation of baseline originate from the change in
      scattering in the skin. The imaginary component enables us to reduce the errors
      in blood glucose prediction. In contrast to the methods using multivariate
      analyses, the calculation process of the blood glucose contents from the measured
      reflection spectra is clear in this method, thus, it is easy to estimate the
      origins of the changes and contributions of the components in the measured
      difference spectra. The proposed method may become a useful tool for realization
      of noninvasive blood glucose prediction using near-infrared spectroscopy.

PMID- 25859837
TI  - A Unique Coexistence of Colonic Collision and Synchronous Tumors!

PMID- 25859838
TI  - Tumor Lysis Syndrome in Metastatic Colon Cancer Following Treatment with
      Regorafenib.

PMID- 25859839
TI  - An Unusual Case of Gastric Cancer with Bone Marrow Metastases and Embolic
      Phenomena as Initial Presentation.

PMID- 25859840
TI  - Gastric Gist with Syncronous Ampullary Gangliocytic Paraganglyoma: A Novel
      Presentation of an Incomplete Carney's Triad.

PMID- 25859842
TI  - An open-label, two-stage, phase II study of bevacizumab and lapatinib in children
      with recurrent or refractory ependymoma: a collaborative ependymoma research
      network study (CERN).
AB  - Co-expression of ERBB2 and ERBB4, reported in 75% of pediatric ependymomas,
      correlates with worse overall survival. Lapatinib, a selective ERBB1 and ERBB2
      inhibitor has produced prolonged disease stabilization in patients with
      ependymoma in a phase I study. Bevacizumab exposure in ependymoma xenografts
      leads to ablation of tumor self-renewing cells, arresting growth. Thus, we
      conducted an open-label, phase II study of bevacizumab and lapatinib in children
      with recurrent ependymomas. Patients <= 21 years of age with recurrent ependymoma
      received lapatinib orally twice daily (900 mg/m(2)/dose to the first 10 patients,
      and then 700 mg/m(2)/dose) and bevacizumab 10 mg/kg intravenously on days 1 and
      15 of a 28-day course. Lapatinib serum trough levels were analyzed prior to each
      course. Total and phosphorylated VEGFR2 expression was measured in peripheral
      blood mononuclear cells (PBMCs) before doses 1 and 2 of bevacizumab and 24-48 h
      following dose 2 of bevacizumab. Twenty-four patients with a median age of 10
      years (range 2-21 years) were enrolled; 22 were eligible and 20 evaluable for
      response. Thirteen had anaplastic ependymoma. There were no objective responses;
      4 patients had stable disease for >= 4 courses (range 4-14). Grade 3 toxicities
      included rash, elevated ALT, and diarrhea. Grade 4 toxicities included peri
      tracheostomy hemorrhage (n = 1) and elevated creatinine phosphokinase (n = 1).
      The median lapatinib pre-dose trough concentration was 3.72 uM. Although the
      combination of bevacizumab and lapatinib was well tolerated in children with
      recurrent ependymoma, it proved ineffective.

PMID- 25859843
TI  - Proton therapy for atypical meningiomas.
AB  - We report clinical outcomes of proton therapy in patients with World Health
      Organization grade 2 (atypical) meningiomas. Between 2005 and 2013, 22 patients
      with atypical meningiomas were treated to a median dose of 63 Gy (RBE) using
      proton therapy, as an adjuvant therapy after surgery (n = 12) or for recurrence
      or progression of residual tumor (n = 10). Six patients had presumed radiation
      induced meningiomas, but none had received prior radiotherapy for their
      meningioma. The median follow-up time after radiation was 39 months (range 7-104)
      and all patients remain alive at last follow-up. The 5-year estimate of local
      control was 71.1% (95% CI 49.3-92.9%). The 5-year estimate of local control was
      87.5% following a radiation dose >60 Gy (RBE), compared to 50.0% for <= 60 Gy
      (RBE) (p = 0.038). The 5-year estimate of neuraxis dissemination was 5% (95% CI 0
      14.6%) and 6.2% (95% CI 0-18.2%) for metastases outside of the central nervous
      system. Radiation necrosis was observed in one patient with a history of prior
      cranial irradiation. Fractionated proton therapy was associated with favorable
      tumor control rates for grade 2 meningiomas. Prospective studies are needed to
      define the optimal radiation dose for high-grade meningiomas.

PMID- 25859841
TI  - Neuroprotective and neurorestorative potential of propargylamine derivatives in
      ageing: focus on mitochondrial targets.
AB  - The mitochondrial theory of ageing proposes that accumulation of damage to
      mitochondrial function and DNA mutation lead to ageing of humans and animals. It
      has been suggested that mitochondria play dynamic roles in regulating
      synaptogenesis and morphological/functional responses of synaptic activity, and
      thus, deteriorating of mitochondrial function (e.g., deficits of the
      mitochondrial respiratory enzymes, reduced calcium influx, increased accumulation
      of mitochondrial DNA defects/apoptotic proteins and impairment of mitochondrial
      membrane potential) can lead to severe neuronal energy deficit, and in the long
      run, to modifications in neuronal synapses and neurodegeneration in the ageing
      brain. Hence, considering the mechanisms by which mitochondrial impairment can
      lead to neuronal death, the development of neuroprotective molecules that target
      various mitochondrial pathogenic processes can be effective in the treatment of
      ageing and age-related neurodegenerative diseases. This review addresses several
      aspects of the neuroprotective effects of propargylamine derivatives (e.g., the
      monoamine oxidase-B inhibitors, selegiline and rasagiline and the multifunctional
      drugs, ladostigil, M30 and VAR10303) in ageing with a special focus on
      mitochondrial molecular protective mechanisms. 

PMID- 25859844
TI  - Overexpression of Roundabout4 predicts poor prognosis of primary glioma patients
      via correlating with microvessel density.
AB  - Roundabout4 (Robo4), a new member of Robo proteins family, is specifically
      expressed in endothelial cells. Recent studies have indicated that Robo4 could
      regulate tumor angiogenesis and vascular permeability. However, the role and
      function of Robo4 are not well understood. This study was performed to
      investigate the expression of Robo4 in primary glioma patients, and thus to
      determine the association of Robo4 expression with microvessel density and
      survival of glioma patients. In this study, real-time PCR and
      immunohistochemistry were performed to examine the mRNA level and protein
      expression of Robo4 in both 43 cases of glioma samples and 10 cases of normal
      brain tissue samples. The results demonstrated that Robo4 was significantly up
      regulated in glioma tissues compared with normal brain tissues. In addition,
      double immunofluorescent staining revealed that Robo4 expression co-localized
      with CD34 expression in the vessel of glioma tissues. The expression of Robo4
      positively correlated with patients' age (P = 0.0139) and glioma grade (P <
      0.0001). A linear correlation was observed between the relative mRNA expression
      of Robo4 values and corresponding microvessel density values (r = 0.9735, P <
      0.0001). Kaplan-Meier analysis and log-rank test result showed that the overall
      survival of patients with Robo4 high expression was significantly shorter than
      that of patients with Robo4 low expression (P < 0.001). The results of present
      study verify that overexpression of Robo4 is related to poor prognosis of primary
      gliomas patients through correlating with microvessel density.

PMID- 25859845
TI  - All effects of psychophysical variables on color attributes: a classification
      system.
AB  - This paper reports the research and structuring of a classification system for
      the effects of psychophysical variables on the color attributes. A basic role of
      color science is to psychophysically specify color appearance. An early stage is
      to specify the effects of the psychophysical variables (as singles, pairs, etc)
      on the color attributes (as singles, pairs, etc), for example to model color
      appearance. Current data on effects are often scarce or conflicting. Few effects
      are well understood, and the practice of naming effects after their discoverer(s)
      is inadequate and can be confusing. The number and types of possible effects have
      never been systematically analyzed and categorized. We propose a simple and
      rigorous system of classification including nomenclature. The total range of
      effects is computed from the possible combinations of three psychophysical
      variables (luminance, dominant wavelength, purity) and six color attributes
      (lightness, brightness, hue, chroma, colorfulness, saturation) in all modes of
      appearance. Omitting those effects that are normally impossible to perceive at
      any one time (such as four- or five-dimensional colors), the total number
      perceivable is 161 types of effects for all modes of appearance. The type of
      effect is named after the psychophysical stimulus (or stimuli) and the relevant
      color attribute(s), e.g., Luminance-on-hue effect (traditionally known as Bezold
      Brucke effect). Each type of effect may include slightly different effects with
      infinite variations depending on experimental parameters. 

PMID- 25859846
TI  - Metabolic dysfunction and altered mitochondrial dynamics in the utrophin
      dystrophin deficient mouse model of duchenne muscular dystrophy.
AB  - The utrophin-dystrophin deficient (DKO) mouse model has been widely used to
      understand the progression of Duchenne muscular dystrophy (DMD). However, it is
      unclear as to what extent muscle pathology affects metabolism. Therefore, the
      present study was focused on understanding energy expenditure in the whole animal
      and in isolated extensor digitorum longus (EDL) muscle and to determine changes
      in metabolic enzymes. Our results show that the 8 week-old DKO mice consume
      higher oxygen relative to activity levels. Interestingly the EDL muscle from DKO
      mouse consumes higher oxygen per unit integral force, generates less force and
      performs better in the presence of pyruvate thus mimicking a slow twitch muscle.
      We also found that the expression of hexokinase 1 and pyruvate kinase M2 was
      upregulated several fold suggesting increased glycolytic flux. Additionally,
      there is a dramatic increase in dynamin-related protein 1 (Drp 1) and mitofusin 2
      protein levels suggesting increased mitochondrial fission and fusion, a feature
      associated with increased energy demand and altered mitochondrial dynamics.
      Collectively our studies point out that the dystrophic disease has caused
      significant changes in muscle metabolism. To meet the increased energetic demand,
      upregulation of metabolic enzymes and regulators of mitochondrial fusion and
      fission is observed in the dystrophic muscle. A better understanding of the
      metabolic demands and the accompanied alterations in the dystrophic muscle can
      help us design improved intervention therapies along with existing drug
      treatments for the DMD patients. 

PMID- 25859848
TI  - Correction: Energy-optimal electrical-stimulation pulses shaped by the least
      action principle.

PMID- 25859849
TI  - Public health and budget impact of probiotics on common respiratory tract
      infections: a modelling study.
AB  - OBJECTIVES: Two recent meta-analyses by the York Health Economics Consortium
      (YHEC) and Cochrane demonstrated probiotic efficacy in reducing the duration and
      number of common respiratory tract infections (CRTI) and associated antibiotic
      prescriptions. A health-economic analysis was undertaken to estimate the public
      health and budget consequences of a generalized probiotic consumption in France.
      METHODS: A virtual age- and gender-standardized population was generated using a
      Markov microsimulation model. CRTI risk factors incorporated into this model were
      age, active/passive smoking and living in a community setting. Incidence rates
      and resource utilization were based on the 2011-2012 flu season and retrieved
      from the French GPs Sentinelles network. Results of both meta-analyses were
      independently applied to the French population to estimate CRTI events, assuming
      a generalized probiotic use compared to no probiotics during winter months: -0.77
      days/CRTI episode (YHEC scenario) or odds-ratio 0.58 for >=1 CRTI episode
      (Cochrane scenario) with vs. without probiotics. Economic perspectives were
      National Health System (NHS), society, family. Outcomes included cost savings
      related to the reduced numbers of CRTI episodes, days of illness, number of
      antibiotic courses, sick leave days, medical and indirect costs. RESULTS: For
      France, generalized probiotic use would save 2.4 million CRTI-days, 291,000
      antibiotic courses and 581,000 sick leave days, based on YHEC data. Applying the
      Cochrane data, reductions were 6.6 million CRTI days, 473,000 antibiotic courses
      and 1.5 million sick days. From the NHS perspective, probiotics' economic impact
      was about ?14.6 million saved according to YHEC and ?37.7 million according to
      Cochrane. Higher savings were observed in children, active smokers and people
      with more frequent human contacts. CONCLUSIONS: Public health and budget impact
      of probiotics are substantial, whether they reduce CRTI episodes frequency or
      duration. Noteworthy, the 2011-12 winter CRTI incidence was low and this analysis
      focused on the fraction of CRTI patients consulting a practitioner.

PMID- 25859847
TI  - Genome wide DNA methylation profiles provide clues to the origin and pathogenesis
      of germ cell tumors.
AB  - The cell of origin of the five subtypes (I-V) of germ cell tumors (GCTs) are
      assumed to be germ cells from different maturation stages. This is (potentially)
      reflected in their methylation status as fetal maturing primordial germ cells are
      globally demethylated during migration from the yolk sac to the gonad. Imprinted
      regions are erased in the gonad and later become uniparentally imprinted
      according to fetal sex. Here, 91 GCTs (type I-IV) and four cell lines were
      profiled (Illumina's HumanMethylation450BeadChip). Data was pre-processed
      controlling for cross hybridization, SNPs, detection rate, probe-type bias and
      batch effects. The annotation was extended, covering snRNAs/microRNAs, repeat
      elements and imprinted regions. A Hidden Markov Model-based genome segmentation
      was devised to identify differentially methylated genomic regions. Methylation
      profiles allowed for separation of clusters of non-seminomas (type II),
      seminomas/dysgerminomas (type II), spermatocytic seminomas (type III) and
      teratomas/dermoid cysts (type I/IV). The seminomas, dysgerminomas and
      spermatocytic seminomas were globally hypomethylated, in line with previous
      reports and their demethylated precursor. Differential methylation and imprinting
      status between subtypes reflected their presumed cell of origin. Ovarian type I
      teratomas and dermoid cysts showed (partial) sex specific uniparental maternal
      imprinting. The spermatocytic seminomas showed uniparental paternal imprinting
      while testicular teratomas exhibited partial imprinting erasure. Somatic
      imprinting in type II GCTs might indicate a cell of origin after global
      demethylation but before imprinting erasure. This is earlier than previously
      described, but agrees with the totipotent/embryonic stem cell like potential of
      type II GCTs and their rare extra-gonadal localization. The results support the
      common origin of the type I teratomas and show strong similarity between ovarian
      type I teratomas and dermoid cysts. In conclusion, we identified specific and
      global methylation differences between GCT subtypes, providing insight into their
      developmental timing and underlying developmental biology. Data and extended
      annotation are deposited at GEO (GSE58538 and GPL18809). 

PMID- 25859850
TI  - Even the smallest non-crop habitat islands could be beneficial: distribution of
      carabid beetles and spiders in agricultural landscape.
AB  - Carabid beetles and ground-dwelling spiders inhabiting agroecosystems are
      beneficial organisms with a potential to control pest species. Intensification of
      agricultural management and reduction of areas covered by non-crop vegetation
      during recent decades in some areas has led to many potentially serious
      environmental problems including a decline in the diversity and abundance of
      beneficial arthropods in agricultural landscapes. This study investigated carabid
      beetle and spider assemblages in non-crop habitat islands of various sizes (50 to
      18,000 square metres) within one large field, as well as the arable land within
      the field, using pitfall traps in two consecutive sampling periods (spring to
      early summer and peak summer). The non-crop habitat islands situated inside
      arable land hosted many unique ground-dwelling arthropod species that were not
      present within the surrounding arable land. Even the smallest non-crop habitat
      islands with areas of tens of square metres were inhabited by assemblages
      substantially different from these inhabiting arable land and thus enhanced the
      biodiversity of agricultural landscapes. The non-crop habitat area substantially
      affected the activity density, recorded species richness and recorded species
      composition of carabid and ground-dwelling spider assemblages; however, the
      effects were weakened when species specialised to non-crop habitats species were
      analysed separately. Interestingly, recorded species richness of spiders
      increased with non-crop habitat area, whereas recorded species richness of
      carabid beetles exhibited an opposite trend. There was substantial temporal
      variation in the spatial distribution of ground-dwelling arthropods, and
      contrasting patterns were observed for particular taxa (carabid beetles and
      spiders). In general, local environmental conditions (i.e., non-crop habitat
      island tree cover, shrub cover, grass cover and litter depth) were better
      determinants of arthropod assemblages than non-crop habitat island size,
      indicating that the creation of quite small but diversified (e.g., differing in
      vegetation cover) non-crop habitat islands could be the most efficient tool for
      the maintenance and enhancement of diversity of ground-dwelling carabids and
      spiders in agricultural landscapes. 

PMID- 25859851
TI  - Specific marker expression and cell state of Schwann cells during culture in
      vitro.
AB  - Schwann cells (SCs) in animals exist in different developmental stages or wound
      repair phases, distinguished mainly by the expression of SC-specific markers. No
      study has yet determined SC state under in vitro culture conditions, and the
      specific markers expressed in SC are obscure as well. In this study, we harvested
      sciatic nerves from newborn mice and isolated SCs by an enzyme-digestion method,
      then we examined the expression profiles of ten markers (S100, p75NTR, Sox10,
      Sox2, GAP43, NCAM, Krox20, Oct6, MBP, and MPZ) at both the RNA and protein levels
      in in vitro mouse SCs and speculated their relation with in vivo SC stages. We
      assayed RNA and protein levels of SC specific markers by immunofluorescence,
      Western Blot, and real-time quantitative RT-PCR. The results show that the
      expression of most markers (S100, p75NTR, GAP43, NCAM, Krox20, Oct6, MBP and MPZ)
      was not detectable in all of early stage cultured SCs. The expression of
      transcription factors Sox10 and Sox2 was, however, detectable in all SCs. After 8
      days, the positive expression rate of all markers except GAP43 and Oct6 was
      almost 100%.These results indicates Sox10 is a necessary marker for SC
      identification, while S100 is not reliable. SCs cultured in vitro express Sox2,
      P75NTR, NCAM, GAP43, Oct6, and MPZ, suggesting that they are similar to in vivo
      undifferentiated iSCs or dedifferentiated iSCs after nerve injury. 

PMID- 25859852
TI  - Carvacrol codrugs: a new approach in the antimicrobial plan.
AB  - OBJECTIVE: The increasing prevalence of antibiotic-resistant bacterial infections
      led to identify alternative strategies for a novel therapeutic approach. In this
      study, we synthesized ten carvacrol codrugs - obtained linking the carvacrol
      hydroxyl group to the carboxyl moiety of sulphur-containing amino acids via an
      ester bond - to develop novel compounds with improved antimicrobial and
      antibiofilm activities and reduced toxicity respect to carvacrol alone. METHOD:
      All carvacrol codrugs were screened against a representative panel of Gram
      positive (S. aureus and S. epidermidis), Gram negative (E. coli and P.
      aeruginosa) bacterial strains and C. albicans, using broth microdilution assays.
      FINDINGS: Results showed that carvacrol codrug 4 possesses the most notable
      enhancement in the anti-bacterial activity displaying MIC and MBC values equal to
      2.5 mg/mL for all bacterial strains, except for P. aeruginosa ATCC 9027 (MIC and
      MBC values equal to 5 mg/mL and 10 mg/mL, respectively). All carvacrol codrugs 1
      10 revealed good antifungal activity against C. albicans ATCC 10231. The
      cytotoxicity assay showed that the novel carvacrol codrugs did not produce human
      blood hemolysis at their MIC values except for codrugs 8 and 9. In particular,
      deepened experiments performed on carvacrol codrug 4 showed an interesting
      antimicrobial effect on the mature biofilm produced by E. coli ATCC 8739, respect
      to the carvacrol alone. The antimicrobial effects of carvacrol codrug 4 were also
      analyzed by TEM evidencing morphological modifications in S. aureus, E. coli, and
      C. albicans. CONCLUSION: The current study presents an insight into the use of
      codrug strategy for developing carvacrol derivatives with antibacterial and
      antibiofilm potentials, and reduced cytotoxicity.

PMID- 25859853
TI  - Supercritical CO2 foaming of thermoplastic materials derived from maize: proof-of
      concept use in mammalian cell culture applications.
AB  - BACKGROUND: Foams are high porosity and low density materials. In nature, they
      are a common architecture. Some of their relevant technological applications
      include heat and sound insulation, lightweight materials, and tissue engineering
      scaffolds. Foams derived from natural polymers are particularly attractive for
      tissue culture due to their biodegradability and bio-compatibility. Here, the
      foaming potential of an extensive list of materials was assayed, including slabs
      elaborated from whole flour, the starch component only, or the protein fraction
      only of maize seeds. METHODOLOGY/PRINCIPAL FINDINGS: We used supercritical CO2 to
      produce foams from thermoplasticized maize derived materials. Polyethylene
      glycol, sorbitol/glycerol, or urea/formamide were used as plasticizers. We report
      expansion ratios, porosities, average pore sizes, pore morphologies, and pore
      size distributions for these materials. High porosity foams were obtained from
      zein thermoplasticized with polyethylene glycol, and from starch
      thermoplasticized with urea/formamide. Zein foams had a higher porosity than
      starch foams (88% and 85%, respectively) and a narrower and more evenly
      distributed pore size. Starch foams exhibited a wider span of pore sizes and a
      larger average pore size than zein (208.84 vs. 55.43 MUm2, respectively). Proof
      of-concept cell culture experiments confirmed that mouse fibroblasts (NIH 3T3)
      and two different prostate cancer cell lines (22RV1, DU145) attached to and
      proliferated on zein foams. CONCLUSIONS/SIGNIFICANCE: We conducted screening and
      proof-of-concept experiments on the fabrication of foams from cereal-based
      bioplastics. We propose that a key indicator of foamability is the strain at
      break of the materials to be foamed (as calculated from stress vs. strain rate
      curves). Zein foams exhibit attractive properties (average pore size, pore size
      distribution, and porosity) for cell culture applications; we were able to
      establish and sustain mammalian cell cultures on zein foams for extended time
      periods.

PMID- 25859854
TI  - The role of temporal abundance structure and habitat preferences in the survival
      of conodonts during the mid-early Silurian Ireviken mass extinction event.
AB  - The Ireviken event was one of the most intense extinction episodes that occurred
      during the mid-Paleozoic era. It had a strong global effect on a range of clades,
      with conodonts, graptolites and chitinozoans affected most. Using geophysical
      proxies and conodont species parameters of their temporal abundance structure we
      investigate how they affected the selectivity of conodont species survival during
      this calamity. After performing bivariate logistic analyses on 34 species of
      conodonts, we find three variables that were statistically significantly
      associated with their odds of survival. These namely include spectral exponents
      that describe degrees of autocorrelation in a time series, the skewness of
      species abundance distribution, and average environmental preferences, which are
      mostly determined by ancient water depths at sampling sites. Model selection of
      multivariate logistic models found the best model includes species local
      abundance skewness and substrate preference. A similar pattern is revealed
      through the regression tree analysis. The apparent extinction selectivity points
      to a possible causes of environmental deterioration during the Ireviken event.
      The significant positive relationship between extinction risk and preferential
      existence in deeper environments suggests the open ocean causal mechanisms of
      biotic stress that occurred during the Ireviken event. Marine regressions, which
      were previously suggested as a causal factor in this extinction episode, on
      theoretical grounds should have had higher impact on species living in near-shore
      environments, through the processes of habitat loss which are associated with
      decreases of shelfal areas. In addition, the significant positive correlations
      found between skewness of abundance distributions and spectral exponent values
      and the probability of species survival suggest that community and ecosystem
      processes (which controlled species abundance fluctuation patterns) were
      significantly related to selectivity processes of this smaller mass extinction
      event. 

PMID- 25859856
TI  - Correction: Molecular and functional analyses of a maize autoactive NB-LRR
      protein identify precise structural requirements for activity.
AB  - [This corrects the article DOI: 10.1371/journal.ppat.1004674.]. 

PMID- 25859855
TI  - The DNA helicase recql4 is required for normal osteoblast expansion and
      osteosarcoma formation.
AB  - RECQL4 mutations are associated with Rothmund Thomson Syndrome (RTS), RAPADILINO
      Syndrome and Baller-Gerold Syndrome. These patients display a range of benign
      skeletal abnormalities such as low bone mass. In addition, RTS patients have a
      highly increased incidence of osteosarcoma (OS). The role of RECQL4 in normal
      adult bone development and homeostasis is largely uncharacterized and how
      mutation of RECQL4 contributes to OS susceptibility is not known. We hypothesised
      that Recql4 was required for normal skeletal development and both benign and
      malignant osteoblast function, which we have tested in the mouse. Recql4 deletion
      in vivo at the osteoblastic progenitor stage of differentiation resulted in mice
      with shorter bones and reduced bone volume, assessed at 9 weeks of age. This was
      associated with an osteoblast intrinsic decrease in mineral apposition rate and
      bone formation rate in the Recql4-deficient cohorts. Deletion of Recql4 in mature
      osteoblasts/osteocytes in vivo, however, did not cause a detectable phenotype.
      Acute deletion of Recql4 in primary osteoblasts or shRNA knockdown in an
      osteoblastic cell line caused failed proliferation, accompanied by cell cycle
      arrest, induction of apoptosis and impaired differentiation. When cohorts of
      animals were aged long term, the loss of Recql4 alone was not sufficient to
      initiate OS. We then crossed the Recql4fl/fl allele to a fully penetrant OS model
      (Osx-Cre p53fl/fl). Unexpectedly, the Osx-Cre p53fl/flRecql4fl/fl (dKO) animals
      had a significantly increased OS-free survival compared to Osx-Cre p53fl/fl or
      Osx-Cre p53fl/flRecql4fl/+ (het) animals. The extended survival was explained
      when the Recql4 status in the tumors that arose was assessed, and in no case was
      there complete deletion of Recql4 in the dKO OS. These data provide a mechanism
      for the benign skeletal phenotypes of RECQL4 mutation syndromes. We propose that
      tumor suppression and osteosarcoma susceptibility are most likely a function of
      mutant, not null, alleles of RECQL4. 

PMID- 25859857
TI  - Could the extent of lymphadenectomy be modified by neoadjuvant chemotherapy in
      cervical cancer? A large-scale retrospective study.
AB  - BACKGROUND: The effect of neoadjuvant chemotherapy (NACT) on topographical
      distribution patterns of lymph node metastasis in cervical cancer was unknown.
      METHODS: Patients with FIGO stage IB1-IIB who underwent radical surgery with or
      without NACT were enrolled (3527 patients). A matched-case comparison design was
      used to compare the effects of NACT on lymph node metastasis. RESULTS: We
      analyzed groups of 167 and 140 patients who were diagnosed with lymph node
      metastasis in the matched primary surgery group and NACT group, respectively, and
      no significant difference was observed (p = 0.081). The incidence of lymph node
      metastasis was significantly decreased in the NACT-responsive group compared to
      the non-responsive group (18.4% vs. 38.6%, P<0.001). The metastatic rates for
      every lymph node group also declined in the NACT-responsive group except for the
      deep inguinal and the para-aortic lymph node groups. Clinical response, deep
      stromal, parametrial and lymph vascular invasions were independent risk factors
      for lymph node metastasis in the NACT group. Furthermore, deep stromal invasion
      and lymph vascular invasion, but not the response to NACT, were independently
      associated with upper LNM. The number of lymph nodes involved, response to NACT,
      tumor histology and a positive vaginal margin were independent prognostic factors
      affecting DFS or OS rates in node-positive patients treated with NACT plus
      radical surgery. CONCLUSION: The frequency and topographic distribution of LNM
      are not modified by NACT, and clinical non-responders showed more involved LNs. A
      systemic and extensive lymphadenectomy should be performed in patients treated
      with NACT plus surgery regardless of the response to NACT.

PMID- 25859859
TI  - Lewontin's paradox resolved? In larger populations, stronger selection erases
      more diversity.
AB  - A new study uses a massive comparative population genetics dataset to explore why
      the neutral genetic diversity of a species does not have a simple relationship to
      its population size. 

PMID- 25859858
TI  - Chimeric antigen receptor-engineered T cells for the treatment of metastatic
      prostate cancer.
AB  - Cancer immunotherapy was selected as the Breakthrough of the Year 2013 by the
      editors of Science, in part because of the successful treatment of refractory
      hematological malignancies with adoptive transfer of chimeric antigen receptor
      (CAR)-engineered T cells. Effective treatment of B cell leukemia may pave the
      road to future treatment of solid tumors, using similar approaches. The prostate
      expresses many unique proteins and, since the prostate gland is a dispensable
      organ, CAR T cells can potentially be used to target these tissue-specific
      antigens. However, the location and composition of prostate cancer metastases
      complicate the task of treating these tumors. It is therefore likely that more
      sophisticated CAR T cell approaches are going to be required for prostate
      metastasis than for B cell malignancies. Two main challenges that need to be
      resolved are how to increase the migration and infiltration of CAR T cells into
      prostate cancer bone metastases and how to counteract the immunosuppressive
      microenvironment found in bone lesions. Inclusion of homing (chemokine) receptors
      in CAR T cells may improve their recruitment to bone metastases, as may antibody
      based combination therapies to normalize the tumor vasculature. Optimal
      activation of CAR T cells through the introduction of multiple costimulatory
      domains would help to overcome inhibitory signals from the tumor
      microenvironment. Likewise, combination therapy with checkpoint inhibitors that
      can reduce tumor immunosuppression may help improve efficacy. Other elegant
      approaches such as induced expression of immune stimulatory cytokines upon target
      recognition may also help to recruit other effector immune cells to metastatic
      sites. Although toxicities are difficult to predict in prostate cancer, severe on
      target/off-tumor toxicities have been observed in clinical trials with use of CAR
      T cells against hematological malignancies; therefore, the choice of the target
      antigen is going to be crucial. This review focuses on different means of
      accomplishing maximal effectiveness of CAR T cell therapy for prostate cancer
      bone metastases while minimizing side effects and CAR T cell-associated
      toxicities. CAR T cell-based therapies for prostate cancer have the potential to
      be a therapy model for other solid tumors. 

PMID- 25859861
TI  - Performance of InsCor and three international scores in cardiac surgery at Santa
      Casa de Marilia.
AB  - OBJECTIVE: To apply and to compare the Society of Thoracic Surgery score (STS),
      EuroSCORE (Eurosc1), EuroSCORE II (Eurosc2) and InsCor (IS) for predicting
      mortality in patients undergoing to coronary artery bypass graft and/or valve
      surgery at the Santa Casa Marilia. METHODS: The present study is a cohort. It is
      a prospective, observational, analytical and unicentric. We analyzed 562
      consecutive patients coronary artery bypass graft and/or valve surgery, between
      April 2011 and June 2013 at the Santa Casa Marilia. Mortality was calculated for
      each patient through the scores STS, Eurosc1, Eurosc2 and IS. The calibration was
      calculated using the Hosmer Lemeshow test and discrimination by ROC curve.
      RESULTS: The hospital mortality was 4,6%. The calibration is generally adequate
      group P=0.345, P=0.765, P=0.272 and P=0.062 for STS, Eurosc1, Eurosc2, and IS
      respectively. The discriminatory power of STS score 0.649 (95% CI 0.529 to 0.770,
      P=0.012), Eurosc1 0.706 (95% CI 0.589 to 0.823, P <=0.001), Eurosc2 was 0.704
      (95% CI 0.590-0.818 P=0.001) and InsCor 0.739 (95% CI 0.638 to 0.839, P <=0.001).
      CONCLUSION: We can say that overall, the InsCor was the best model, mainly in the
      discrimination of the sample. The InsCor showed good accuracy, in addition to
      being effective and easy to apply, especially by using a smaller number of
      variables compared to the other models.

PMID- 25859862
TI  - Determinants of peak VO2 in heart transplant recipients.
AB  - OBJECTIVE: To establish the determinants of the peak VO2 in heart transplant
      recipients. METHODS: Patient's assessment was performed in two consecutive days.
      In the first day, patients performed the heart rate variability assessment
      followed by a cardiopulmonary exercise test. In the second day, patients
      performed a resting echocardiography. Heart transplant recipients were eligible
      if they were in a stable condition and without any evidence of tissue rejection
      diagnosed by endomyocardial biopsy. Patients with pacemaker, noncardiovascular
      functional limitations such as osteoarthritis and chronic obstructive pulmonary
      disease were excluded from this study. RESULTS: Sixty patients (68% male, 48
      years and 64 months following heart transplantation) were assessed. Multivariate
      analysis selected the following variables: receptor's gender (P=0.001), receptor
      age (P=0.049), receptor Body Mass Index (P=0.005), heart rate reserve (P
      <0.0001), left atrium diameter (P=0.016). Multivariate analysis showed r=0.77 and
      r2=0.6 with P <0.001. Equation: peakVO2=32.851 - 3.708 (receptor gender) - 0.067
      (receptor age) - 0.318 (receptor BMI) + 0.145 (heart rate reserve) - 0.111 (left
      atrium diameter). CONCLUSION: The determinants of the peak VO2 in heart
      transplant recipients were: receptor sex, age, Body Mass Index, heart rate
      reserve and left atrium diameter. Heart rate reserve was the unique variable
      positively associated with peak VO2. This data suggest the importance of the
      sympathetic reinnervation in peak VO2 in heart transplant recipients.

PMID- 25859860
TI  - Role of complement and complement regulatory proteins in the complications of
      diabetes.
AB  - It is well established that the organ damage that complicates human diabetes is
      caused by prolonged hyperglycemia, but the cellular and molecular mechanisms by
      which high levels of glucose cause tissue damage in humans are still not fully
      understood. The prevalent hypothesis explaining the mechanisms that may underlie
      the pathogenesis of diabetes complications includes overproduction of reactive
      oxygen species, increased flux through the polyol pathway, overactivity of the
      hexosamine pathway causing intracellular formation of advanced glycation end
      products, and activation of protein kinase C isoforms. In addition, experimental
      and clinical evidence reported in past decades supports a strong link between the
      complement system, complement regulatory proteins, and the pathogenesis of
      diabetes complications. In this article, we summarize the body of evidence that
      supports a role for the complement system and complement regulatory proteins in
      the pathogenesis of diabetic vascular complications, with specific emphasis on
      the role of the membrane attack complex (MAC) and of CD59, an extracellular cell
      membrane-anchored inhibitor of MAC formation that is inactivated by nonenzymatic
      glycation. We discuss a pathogenic model of human diabetic complications in which
      a combination of CD59 inactivation by glycation and hyperglycemia-induced
      complement activation increases MAC deposition, activates pathways of
      intracellular signaling, and induces the release of proinflammatory,
      prothrombotic cytokines and growth factors. Combined, complement-dependent and
      complement-independent mechanisms induced by high glucose promote inflammation,
      proliferation, and thrombosis as characteristically seen in the target organs of
      diabetes complications. 

PMID- 25859863
TI  - Evaluation of the prevalence of stress and its phases in acute myocardial
      infarction in patients active in the labor market.
AB  - INTRODUCTION: Acute myocardial infarction is a social health problem of
      epidemiological relevance, with high levels of morbidity and mortality. Stress is
      one of the modifiable risk factors that triggers acute myocardial infarction.
      Stress is a result of a set of physiological reactions, which when exaggerated in
      intensity or duration can lead to imbalances in one's organism, resulting in
      vulnerability to diseases. OBJECTIVE: To identify the presence of stress and its
      phases in hospitalized and active labor market patients with unstable myocardial
      infarction and observe its correlation with the life of this population with
      stress. METHODS: The methodology used was a quantitative, descriptive and
      transversal research approach conducted with a total of 43 patients, who were
      still active in the labor market, presenting or not morbidities. Data collection
      occurred on the fourth day of their hospitalization and patients responded to
      Lipp's Stress Symptom Inventory for adults. RESULTS: Thirty-one patients (72.1%)
      presented stress and twelve (27.8%) did not. In patients with stress, the
      identified phases were: alert - one patient (3.2%); resistance -twenty-two
      patients (71.0%); quasi-exhaustion - six patients (19.4%) and exhaustion - two
      patients (6.5%). All women researched presented stress. CONCLUSION: The results
      suggest a high level of stress, especially in the resistance phase, in the male
      infarcted population, hospitalized and active in the labor market.

PMID- 25859864
TI  - Risk factors for transient dysfunction of gas exchange after cardiac surgery.
AB  - OBJECTIVE: A retrospective cohort study was preformed aiming to verify the
      presence of transient dysfunction of gas exchange in the postoperative period of
      cardiac surgery and determine if this disorder is linked to cardiorespiratory
      events. METHODS: We included 942 consecutive patients undergoing cardiac surgery
      and cardiac procedures who were referred to the Intensive Care Unit between June
      2007 and November 2011. RESULTS: Fifteen patients had acute respiratory distress
      syndrome (2%), 199 (27.75%) had mild transient dysfunction of gas exchange, 402
      (56.1%) had moderate transient dysfunction of gas exchange, and 39 (5.4%) had
      severe transient dysfunction of gas exchange. Hypertension and cardiogenic shock
      were associated with the emergence of moderate transient dysfunction of gas
      exchange postoperatively (P=0.02 and P=0.019, respectively) and were risk factors
      for this dysfunction (P=0.0023 and P=0.0017, respectively). Diabetes mellitus was
      also a risk factor for transient dysfunction of gas exchange (P=0.03). Pneumonia
      was present in 8.9% of cases and correlated with the presence of moderate
      transient dysfunction of gas exchange (P=0.001). Severe transient dysfunction of
      gas exchange was associated with patients who had renal replacement therapy
      (P=0.0005), hemotherapy (P=0.0001), enteral nutrition (P=0.0012), or cardiac
      arrhythmia (P=0.0451). CONCLUSION: Preoperative hypertension and cardiogenic
      shock were associated with the occurrence of postoperative transient dysfunction
      of gas exchange. The preoperative risk factors included hypertension, cardiogenic
      shock, and diabetes. Postoperatively, pneumonia, ventilator-associated pneumonia,
      renal replacement therapy, hemotherapy, and cardiac arrhythmia were associated
      with the appearance of some degree of transient dysfunction of gas exchange,
      which was a risk factor for reintubation, pneumonia, ventilator-associated
      pneumonia, and renal replacement therapy in the postoperative period of cardiac
      surgery and cardiac procedures.

PMID- 25859865
TI  - Epidemiology of coronary artery bypass grafting at the Hospital Beneficencia
      Portuguesa, Sao Paulo.
AB  - INTRODUCTION: The knowledge of the prevalence of risk factors and comorbidities,
      as well as the evolution and complications in patients undergoing coronary artery
      bypass graft allows comparison between institutions and evidence of changes in
      the profile of patients and postoperative evolution over time. OBJECTIVE: To
      profile (risk factors and comorbidities) and clinical outcome (complications) in
      patients undergoing coronary artery bypass graft in a national institution of
      great surgical volume. METHODS: A retrospective cohort study of patients
      undergoing coronary artery bypass graft in the hospital Beneficencia Portuguesa
      de Sao Paulo, from July 2009 to July 2010. RESULTS: We included 3,010 patients,
      mean age of 62.2 years and 69.9% male. 83.8% of patients were hypertensive, 36.6%
      diabetic, 44.5% had dyslipidemia, 15.3% were smokers, 65.7% were
      overweight/obese, 29.3% had a family history of coronary heart disease. The
      expected mortality calculated by logistic EuroSCORE was 2.7%. The isolated CABG
      occurred in 89.3% and 11.9% surgery was performed without cardiopulmonary bypass.
      The most common complication was cardiac arrhythmia (18.7%), especially acute
      atrial fibrillation (14.3%). Pneumonia occurred in 6.2% of patients, acute renal
      failure in 4.4%, mediastinites in 2.1%, stroke in 1.8% and AMI in 1.2%. The in
      hospital mortality was 5.4% and in isolated coronary artery bypass graft was
      3.5%. The average hospital stay was 11 days with a median of eight days (3-244
      days). CONCLUSION: The profile of patients undergoing coronary artery bypass
      graft surgery in this study is similar to other published studies.

PMID- 25859866
TI  - Analysis of steps adapted protocol in cardiac rehabilitation in the hospital
      phase.
AB  - OBJECTIVE: To analyze a cardiac rehabilitation adapted protocol in physical
      therapy during the postoperative hospital phase of cardiac surgery in a service
      of high complexity, in aspects regarded to complications and mortality prevalence
      and hospitalization days. METHODS: This is an observational cross-sectional,
      retrospective and analytical study performed by investigating 99 patients who
      underwent cardiac surgery for coronary artery bypass graft, heart valve
      replacement or a combination of both. Step program adapted for rehabilitation
      after cardiac surgery was analyzed under the command of the physiotherapy
      professional team. RESULTS: In average, a patient stays for two days in the
      Intensive Care Unit and three to four days in the hospital room, totalizing six
      days of hospitalization. Fatalities occurred in a higher percentage during
      hospitalization (5.1%) and up to two years period (8.6%) when compared to 30 days
      after hospital discharge (1.1%). Among the postoperative complications, the
      hemodynamic (63.4%) and respiratory (42.6%) were the most prevalent. 36-42% of
      complications occurred between the immediate postoperative period and the second
      postoperative day. The hospital discharge started from the fifth postoperative
      day. We can observe that in each following day, the patients are evolving in
      achieving the Steps, where Step 3 was the most used during the rehabilitation
      phase I. CONCLUSION: This evolution program by steps can to guide the physical
      rehabilitation at the hospital in patients after cardiac surgery.

PMID- 25859867
TI  - Perioperative myocardial infarction in patients undergoing myocardial
      revascularization surgery.
AB  - INTRODUCTION: Perioperative myocardial infarction adversely affects the prognosis
      of patients undergoing coronary artery bypass graft and its diagnosis was
      hampered by numerous difficulties, because the pathophysiology is different from
      the traditional instability atherosclerotic and the clinical difficulty to be
      characterized. OBJECTIVE: To identify the frequency of perioperative myocardial
      infarction and its outcome in patients undergoing coronary artery bypass graft.
      METHODS: Retrospective cohort study performed in a tertiary hospital specialized
      in cardiology, from May 01, 2011 to April 30, 2012, which included all records
      containing coronary artery bypass graft records. To confirm the diagnosis of
      perioperative myocardial infarction criteria, the Third Universal Definition of
      Myocardial Infarction was used. RESULTS: We analyzed 116 cases. Perioperative
      myocardial infarction was diagnosed in 28 patients (24.1%). Number of grafts and
      use and cardiopulmonary bypass time were associated with this diagnosis and the
      mean age was significantly higher in this group. The diagnostic criteria elevated
      troponin I, which was positive in 99.1% of cases regardless of diagnosis of
      perioperative myocardial infarction. No significant difference was found between
      length of hospital stay and intensive care unit in patients with and without this
      complication, however patients with perioperative myocardial infarction
      progressed with worse left ventricular function and more death cases. CONCLUSION:
      The frequency of perioperative myocardial infarction found in this study was
      considered high and as a consequence the same observed average higher troponin I,
      more cases of worsening left ventricular function and death.

PMID- 25859868
TI  - Abnormal heart rate variability and atrial fibrillation after aortic surgery.
AB  - INTRODUCTION: Complete denervation of transplanted heart exerts protective effect
      against postoperative atrial fibrillation; various degrees of autonomic
      denervation appear also after transection of ascending aorta during surgery for
      aortic aneurysm. OBJECTIVE: This study aimed to evaluate if the level of cardiac
      denervation obtained by resection of ascending aorta could exert any effect on
      postoperative atrial fibrillation incidence. METHODS: We retrospectively analysed
      the clinical records of 67 patients submitted to graft replacement of ascending
      aorta (group A) and 132 with aortic valve replacement (group B); all episodes of
      postoperative atrial fibrillation occurred during the 1-month follow-up have been
      reported. Heart Rate Variability parameters were obtained from a 24-h Holter
      recording; clinical, echocardiographic and treatment data were also evaluated.
      RESULTS: Overall, 45% of patients (group A 43%, group B 46%) presented at least
      one episode of postoperative atrial fibrillation. Older age (but not gender,
      abnormal glucose tolerance, ejection fraction, left atrial diameter) was
      correlated with incidence of postoperative atrial fibrillation. Only among a
      subgroup of patients with aortic transection and signs of greater autonomic
      derangement (heart rate variability parameters below the median and mean heart
      rate over the 75th percentile), possibly indicating more profound autonomic
      denervation, a lower incidence of postoperative atrial fibrillation was observed
      (22% vs. 54%). CONCLUSION: Transection of ascending aorta for repair of an aortic
      aneurysm did not confer any significant protective effect from postoperative
      atrial fibrillation in comparison to patients with intact ascending aorta. It
      could be speculated that a limited and heterogeneous cardiac denervation was
      produced by the intervention, creating an eletrophysiological substrate for the
      high incidence of postoperative atrial fibrillation observed.

PMID- 25859869
TI  - Morphological description of great cardiac vein in pigs compared to human hearts.
AB  - INTRODUCTION: In spite of its importance as an experimental model, the
      information on the great cardiac vein in pigs is sparse. OBJECTIVE: To determine
      the morphologic characteristics of the great cardiac vein and its tributaries in
      pigs. METHODS: 120 hearts extracted from pigs destined to the slaughterhouse with
      stunning method were studied. This descriptive cross-over study evaluated
      continuous variables with T test and discrete variables with Pearson chi square
      test. A level of significance P<0.05 was used. The great cardiac vein and its
      tributaries were perfused with polyester resin (85% Palatal and 15% Styrene) and
      then subjected to potassium hydroxide infusion to release the subepicardial fat.
      Calibers were measured, and trajectories and relations with adjacent arterial
      structures were evaluated. RESULTS: The origin of the great cardiac vein was
      observed at the heart apex in 91 (76%) hearts. The arterio-venous trigone was
      present in 117 (97.5%) specimens, corresponding to the open expression in its
      lower segment and to the closed expression in the upper segment in the majority
      of the cases (65%). The caliber of the great cardiac vein at the upper segment of
      the paraconal interventricular sulcus was 3.73+/-0.79 mm. An anastomosis between
      the great cardiac vein and the middle cardiac vein was found in 59 (49%)
      specimens. CONCLUSION: The morphological and biometric characteristics of the
      great cardiac vein and its tributaries had not been reported in prior studies,
      and due to their similitude with those of the human heart, allows us to propose
      the pig model for procedural and hemodynamic applications.

PMID- 25859870
TI  - Are there gender differences in left ventricular remodeling after myocardial
      infarction in rats?
AB  - OBJECTIVE: An unclear issue is whether gender may influence at cardiac remodeling
      after myocardial infarction (MI). We evaluated left ventricle remodeling in
      female and male rats post-MI. METHODS: Rats were submitted to anterior descending
      coronary occlusion. Echocardiographic evaluations were performed on the first and
      sixth week post-occlusion to determine myocardial infarction size and left
      ventricle systolic function (FAC, fractional area change). Pulsed Doppler was
      applied to analyze left ventricle diastolic function using the following
      parameters: E wave, A wave, E/A ratio. Two-way ANOVA was applied for comparisons,
      complemented by the Bonferroni test. A P<==0.05 was considered significant.
      RESULTS: There were no significant differences between genders for morphometric
      parameters on first (MI [Female (FE): 44.0 +/- 5.0 vs. Male (MA): 42.0 +/- 3.0%];
      diastolic [FE: 0.04 +/- 0.003 vs. MA: 0.037 +/- 0.005, mm/g] and systolic [FE:
      0.03 +/- 0.0004 vs. MA: 0.028 +/- 0.005, mm/g] diameters of left ventricle) and
      sixth (MI [FE: 44.0 +/- 5.0 vs. MA: 42.0 +/- 3.0, %]; diastolic [FE: 0.043 +/-
      0.01 vs. MA: 0.034 +/- 0.005, mm/g] and systolic [FE: 0.035 +/- 0.01 vs. MA:
      0.027 +/- 0.005, mm/g] of LV) week. Similar findings were reported for left
      ventricle functional parameters on first (FAC [FE: 34.0 +/- 6.0 vs. MA: 32.0 +/-
      4.0, %]; wave E [FE: 70.0 +/- 18.0 vs. MA: 73.0 +/- 14.0, cm/s]; wave A [FE: 20.0
      +/- 12.0 vs. MA: 28.0 +/- 13.0, cm/s]; E/A [FE: 4.9 +/- 3.4 vs. MA: 3.3 +/- 1.8])
      and sixth (FAC [FE: 29.0 +/- 7.0 vs. MA: 31.0 +/- 7.0, %]; wave E [FE: 85.0 +/-
      18.0 vs. MA: 87.0 +/- 20.0, cm/s]; wave A [FE: 20.0 +/- 11.0 vs. MA: 28.0 +/-
      17.0, cm/s]; E/A [FE: 6.2 +/- 4.0 vs. MA: 4.6 +/- 3.4]) week. CONCLUSION: Gender
      does not influence left ventricle remodeling post-MI in rats.

PMID- 25859871
TI  - Thymoquinone protects end organs from abdominal aorta ischemia/reperfusion injury
      in a rat model.
AB  - INTRODUCTION: Previous studies have demonstrated that thymoquinone has protective
      effects against ischemia reperfusion injury to various organs like lungs, kidneys
      and liver in different experimental models. OBJECTIVE: We aimed to determine
      whether thymoquinone has favorable effects on lung, renal, heart tissues and
      oxidative stress in abdominal aorta ischemia-reperfusion injury. METHODS: Thirty
      rats were divided into three groups as sham (n=10), control (n=10) and
      thymoquinone (TQ) treatment group (n=10). Control and TQ-treatment groups
      underwent abdominal aorta ischemia for 45 minutes followed by a 120-min period of
      reperfusion. In the TQ-treatment group, thymoquinone was given 5 minutes. before
      reperfusion at a dose of 20 mg/kg via an intraperitoneal route. Total antioxidant
      capacity, total oxidative status (TOS), and oxidative stress index (OSI) in blood
      serum were measured and lung, kidney, and heart tissue histopathology were
      evaluated with light microscopy. RESULTS: Total oxidative status and oxidative
      stress index activity in blood samples were statistically higher in the control
      group compared to the sham and TQ-treatment groups (P<0.001 for TOS and OSI).
      Control group injury scores were statistically higher compared to sham and TQ
      treatment groups (P<0.001 for all comparisons). CONCLUSION: Thymoquinone
      administered intraperitoneally was effective in reducing oxidative stress and
      histopathologic injury in an acute abdominal aorta ischemia-reperfusion rat
      model.

PMID- 25859872
TI  - Twenty years of vasoplegic syndrome treatment in heart surgery. Methylene blue
      revised.
AB  - OBJECTIVE: This study was conducted to reassess the concepts established over the
      past 20 years, in particular in the last 5 years, about the use of methylene blue
      in the treatment of vasoplegic syndrome in cardiac surgery. METHODS: A wide
      literature review was carried out using the data extracted from: MEDLINE, SCOPUS
      and ISI WEB OF SCIENCE. RESULTS: The reassessed and reaffirmed concepts were 1)
      MB is safe in the recommended doses (the lethal dose is 40 mg/kg); 2) MB does not
      cause endothelial dysfunction; 3) The MB effect appears in cases of NO up
      regulation; 4) MB is not a vasoconstrictor, by blocking the cGMP pathway it
      releases the cAMP pathway, facilitating the norepinephrine vasoconstrictor
      effect; 5) The most used dosage is 2 mg/kg as IV bolus, followed by the same
      continuous infusion because plasma concentrations sharply decrease in the first
      40 minutes; and 6) There is a possible "window of opportunity" for MB's
      effectiveness. In the last five years, major challenges were: 1) Observations
      about side effects; 2) The need for prophylactic and therapeutic guidelines, and;
      3) The need for the establishment of the MB therapeutic window in humans.
      CONCLUSION: MB action to treat vasoplegic syndrome is time-dependent. Therefore,
      the great challenge is the need, for the establishment the MB therapeutic window
      in humans. This would be the first step towards a systematic guideline to be
      followed by possible multicenter studies.

PMID- 25859873
TI  - Mycobacterial endocarditis: a comprehensive review.
AB  - OBJECTIVE: A systematic analysis was made in view of the epidemiology, clinical
      features, diagnosis, treatment and main outcomes of mycobacterial endocarditis.
      METHODS: The data source of the present study was based on a comprehensive
      literature search in MEDLINE, Highwire Press and Google search engine for
      publications on mycobacterial endocarditis published between 2000 and 2013.
      RESULTS: The rapidly growing mycobacteria become the predominant pathogens with
      Mycobacterium chelonae being the most common. This condition has changed
      significantly in terms of epidemiology since the 21st century, with more broad
      patient age range, longer latency, prevailed mitral valve infections and better
      prognosis. CONCLUSION: Mycobacterial endocarditis is rare and the causative
      pathogens are predominantly the rapidly growing mycobacteria. Amikacin,
      ciprofloxacin and clarithromycin are the most frequently used targeted
      antimicrobial agents but often show poor responses. Patients with deep infections
      may warrant a surgical operation or line withdrawal. With periodic multidrug
      therapy guided by drug susceptibility testing, and surgical managements, patients
      may achieve good therapeutic results.

PMID- 25859874
TI  - Barriers to development: pushing the boundaries.
AB  - Why some countries have failed to create democracy, wealth and happiness for
      their people is one of the great questions of our time. This essay encompasses a
      description of the multiple barriers to development that may have different
      characteristics, according to the context and the social structures that maintain
      these conditions. It would be arrogant to pretend to have all the solutions for
      these problems. 

PMID- 25859875
TI  - A new classification of post-sternotomy dehiscence.
AB  - The dehiscence after median transesternal sternotomy used as surgical access for
      cardiac surgery is one of its complications and it increases the patient's
      morbidity and mortality. A variety of surgical techniques were recently described
      resulting to the need of a classification bringing a measure of objectivity to
      the management of these complex and dangerous wounds. The different related
      classifications are based in the primary causal infection, but recently the
      anatomical description of the wound including the deepness and the vertical
      extension showed to be more useful. We propose a new classification based only on
      the anatomical changes following sternotomy dehiscence and chronic wound
      formation separating it in four types according to the deepness and in two sub
      groups according to the vertical extension based on the inferior insertion of the
      pectoralis major muscle. 

PMID- 25859877
TI  - Is clinical treatment the gold standard in the treatment of acute type B aortic
      dissections?

PMID- 25859876
TI  - Comparison of polyurethane with cyanoacrylate in hemostasis of vascular injury in
      guinea pigs.
AB  - OBJECTIVE: To evaluate the behavior of castor oil-derived polyurethane as a
      hemostatic agent and tissue response after abdominal aortic injury and to compare
      it with 2-octyl-cyanoacrylate. METHODS: Twenty-four Guinea Pigs were randomly
      divided into three groups of eight animals (I, II, and III). The infrarenal
      abdominal aorta was dissected, clamped proximally and distally to the vascular
      puncture site. In group I (control), hemostasis was achieved with digital
      pressure; in group II (polyurethane) castor oil-derived polyurethane was applied,
      and in group III (cyanoacrylate), 2-octyl-cyanoacrylate was used. Group II was
      subdivided into IIA and IIB according to the time of preparation of the
      hemostatic agent. RESULTS: Mean blood loss in groups IIA, IIB and III was 0.002
      grams (g), 0.008 g, and 0.170 g, with standard deviation of 0.005 g, 0.005 g, and
      0.424 g, respectively (P=0.069). The drying time for cyanoacrylate averaged 81.5
      seconds (s) (standard deviation: 51.5 seconds) and 126.1 s (standard deviation:
      23.0 s) for polyurethane B (P=0.046). However, there was a trend (P=0.069) for
      cyanoacrylate to dry more slowly than polyurethane A (mean: 40.5 s; SD: 8.6 s).
      Furthermore, polyurethane A had a shorter drying time than polyurethane B
      (P=0.003), mean IIA of 40.5 s (standard deviation: 8.6 s). In group III, 100% of
      the animals had mild/severe fibrosis, while in group II only 12.5% showed this
      degree of fibrosis (P=0.001). CONCLUSION: Polyurethane derived from castor oil
      showed similar hemostatic behavior to octyl-2-cyanoacrylate. There was less
      perivascular tissue response with polyurethane when compared with cyanoacrylate.

PMID- 25859878
TI  - BJCVS/RBCCV and endnote.

PMID- 25859879
TI  - English: the new official language of BJCVS.

PMID- 25859880
TI  - TRALI or ARDS or TDGE versus blood transfusion.

PMID- 25859881
TI  - Fetal cardiac tumors: prenatal diagnosis and outcomes.

PMID- 25859882
TI  - Effectiveness of a cardiac rehabilitation program during hospital stay.

PMID- 25859883
TI  - Structure-Independent Proton Transport in Cerium(III) Phosphate Nanowires.
AB  - Understanding of water-related electrical conduction is of utmost importance in
      applications that utilize solid-state proton conductors. However, in spite of the
      vast amount of theoretical and experimental work published in the literature,
      thus far its mechanism remained unsolved. In this study, the structure-related
      ambient temperature electrical conduction of one-dimensional hydrophilic
      nanostructures was investigated. Cerium phosphate nanowires with monoclinic and
      hexagonal crystal structures were synthesized via the hydrothermal and ambient
      temperature precipitation routes, and their structural and surface properties
      were examined by using high-resolution transmission electron microscopy, X-ray
      diffractometry, nitrogen and water sorption, temperature-programmed ammonia
      desorption, and potentiometric titration techniques. The relative humidity (RH)
      dependent charge-transport processes of hexagonal and monoclinic nanowires were
      investigated by means of impedance spectroscopy and transient ionic current
      measurement techniques to gain insight into their atomistic level mechanism.
      Although considerable differences in RH-dependent conductivity were first found,
      the distinct characteristics collapsed into a master curve when specific surface
      area and acidity were taken into account, implying structure-independent proton
      conduction mechanism in both types of nanowires. 

PMID- 25859885
TI  - The health impact of nighttime eating: old and new perspectives.
AB  - Nighttime eating, particularly before bed, has received considerable attention.
      Limiting and/or avoiding food before nighttime sleep has been proposed as both a
      weight loss strategy and approach to improve health and body composition. Indeed,
      negative outcomes have been demonstrated in response to large mixed meals in
      populations that consume a majority of their daily food intake during the night.
      However, data is beginning to mount to suggest that negative outcomes may not be
      consistent when the food choice is small, nutrient-dense, low energy foods and/or
      single macronutrients rather than large mixed-meals. From this perspective, it
      appears that a bedtime supply of nutrients can promote positive physiological
      changes in healthy populations. In addition, when nighttime feeding is combined
      with exercise training, any adverse effects appear to be eliminated in obese
      populations. Lastly, in Type I diabetics and those with glycogen storage disease,
      eating before bed is essential for survival. Nevertheless, nighttime consumption
      of small (~150 kcals) single nutrients or mixed-meals does not appear to be
      harmful and may be beneficial for muscle protein synthesis and cardiometabolic
      health. Future research is warranted to elucidate potential applications of
      nighttime feeding alone and in combination with exercise in various populations
      of health and disease. 

PMID- 25859886
TI  - 3-Fluoroazetidinecarboxylic Acids and trans,trans-3,4-Difluoroproline as Peptide
      Scaffolds: Inhibition of Pancreatic Cancer Cell Growth by a Fluoroazetidine
      Iminosugar.
AB  - Reverse aldol opening renders amides of 3-hydroxyazetidinecarboxylic acids (3-OH
      Aze) unstable above pH 8. Aze, found in sugar beet, is mis-incorporated for
      proline in peptides in humans and is associated with multiple sclerosis and
      teratogenesis. Aze-containing peptides may be oxygenated by prolyl hydroxylases
      resulting in potential damage of the protein by a reverse aldol of the
      hydroxyazetidine; this, rather than changes in conformation, may account for the
      deleterious effects of Aze. This paper describes the synthesis of 3-fluoro-Aze
      amino acids as hydroxy-Aze analogues which are not susceptible to aldol cleavage.
      4-(Azidomethyl)-3-fluoro-Aze and 3,4-difluoroproline are new peptide building
      blocks. trans,trans-2,4-Dihydroxy-3-fluoroazetidine, an iminosugar, inhibits the
      growth of pancreatic cancer cells to a similar degree as gemcitabine. 

PMID- 25859887
TI  - Tailgut cysts in children: a report of two cases and literature review.
AB  - Tailgut cysts are rare congenital lesions that typically manifest as a presacral,
      retrorectal, multicystic mass. Even though they are derived from remnants of the
      embryonic tailgut, they most often present in women. Differential diagnosis
      includes rectal duplication cyst, sacrococcygeal teratoma, and anterior
      meningocele. Treatment demands complete excision to prevent infection and
      malignant degeneration. Fewer than 20 pediatric cases have been reported. Two
      further affected children are described, one of whom presented uniquely with
      urinary tract obstruction and acute renal failure. 

PMID- 25859888
TI  - Contaminant deposition building shielding factors for US residential structures.
AB  - This paper presents validated building shielding factors designed for
      contemporary US housing-stock under an idealized, yet realistic, exposure
      scenario from contaminant deposition on the roof and surrounding surfaces. The
      building shielding factors are intended for use in emergency planning and level
      three probabilistic risk assessments for a variety of postulated radiological
      events in which a realistic assessment is necessary to better understand the
      potential risks for accident mitigation and emergency response planning. Factors
      are calculated from detailed computational housing-units models using the general
      purpose Monte Carlo N-Particle computational code, MCNP5, and are benchmarked
      from a series of narrow- and broad-beam measurements analyzing the shielding
      effectiveness of ten common general-purpose construction materials and ten
      shielding models representing the primary weather barriers (walls and roofs) of
      likely US housing-stock. Each model was designed to scale based on common
      residential construction practices and include, to the extent practical, all
      structurally significant components important for shielding against ionizing
      radiation. Calculations were performed for floor-specific locations from
      contaminant deposition on the roof and surrounding ground as well as for
      computing a weighted-average representative building shielding factor for single-
      and multi-story detached homes, both with and without basement as well for single
      wide manufactured housing-unit. 

PMID- 25859884
TI  - Inflammaging and cancer: a challenge for the Mediterranean diet.
AB  - Aging is considered the major risk factor for cancer, one of the most important
      mortality causes in the western world. Inflammaging, a state of chronic, low
      level systemic inflammation, is a pervasive feature of human aging. Chronic
      inflammation increases cancer risk and affects all cancer stages, triggering the
      initial genetic mutation or epigenetic mechanism, promoting cancer initiation,
      progression and metastatic diffusion. Thus, inflammaging is a strong candidate to
      connect age and cancer. A corollary of this hypothesis is that interventions
      aiming to decrease inflammaging should protect against cancer, as well as
      most/all age-related diseases. Epidemiological data are concordant in suggesting
      that the Mediterranean Diet (MD) decreases the risk of a variety of cancers but
      the underpinning mechanism(s) is (are) still unclear. Here we review data
      indicating that the MD (as a whole diet or single bioactive nutrients typical of
      the MD) modulates multiple interconnected processes involved in carcinogenesis
      and inflammatory response such as free radical production, NF-kappaB activation
      and expression of inflammatory mediators, and the eicosanoids pathway. Particular
      attention is devoted to the capability of MD to affect the balance between pro-
      and anti-inflammaging as well as to emerging topics such as maintenance of gut
      microbiota (GM) homeostasis and epigenetic modulation of oncogenesis through
      specific microRNAs. 

PMID- 25859889
TI  - Which incentive package will retain regionalized health personnel in Burkina
      Faso: a discrete choice experiment.
AB  - BACKGROUND: The lack of motivation of health workers to practice in rural areas
      remains a crucial problem for decision-makers, as it deprives the majority of
      access to health care. To solve the problem, many countries have implemented
      health worker retention strategies. However, the development of such strategies
      requires an understanding of the preferences of health workers. The objective of
      the study was to identify a package for attracting and retaining health workers
      in underserved areas. METHODS: A cross sectional study was conducted in three
      health regions of Burkina Faso in 2012. A discrete choice experiment was used to
      investigate preferences for incentive packages among health workers recruited
      under the regionalized policy. In-depth interviews and focus group discussions
      with health workers currently working in the East and Sahel regions and policy
      makers, and a literature review on attraction and retention in low income
      countries, were performed to identify the attributes and levels. These attributes
      were: the regionalized recruitment policy, health insurance, work equipment,
      housing, and specific incentive compensation. The final design resulted in 16
      choice sets. A multinomial logistic regression was used to determine the
      influence of socio-demographic characteristics on choice of a given option. A
      probit logistic regression model was then used to analyze the effect of these
      difference variables on choice, to identify the incentive package best suited to
      health workers. In total, questionnaires were administered to 315 regional health
      workers. RESULTS: For all participants, choice of package was strongly influenced
      by length of commitment under the policy and provision of housing. Sex, number of
      years in profession, and location also influenced the choice of package. Women
      are twice more likely to choose a package with free housing and the cancellation
      of the policy. CONCLUSION: It is important that governments consider health
      worker preferences in crafting policies to address attraction and retention in
      underserved areas. In addition, the methodology of discrete choice experiment has
      been particularly useful, not only for better understanding the factors
      explaining the reluctance of health workers to work in underserved areas, but
      also to provide practical advice to the government, to improve its retention
      policy.

PMID- 25859891
TI  - Violence and violence prevention: New roles for child and adolescent mental
      health practitioners.

PMID- 25859892
TI  - Professional services for child rape survivors: A child-centred perspective on
      helpful and harmful experiences.
AB  - OBJECTIVE: The aim of this study was to explore child rape survivors' perceptions
      of helpful and harmful experiences at the hands of professional service
      providers. METHOD: Focused interviews were conducted with a convenience sample of
      20 child rape survivors who had presented for counselling services at a non
      governmental organisation located in the coastal region of KwaZulu-Natal, South
      Africa. For each case, information was obtained regarding children's perceptions
      of helpful and harmful experiences at the hands of police, medical and criminal
      justice system personnel. RESULTS: A thematic analysis of children's responses
      indicated that the concerns expressed by respondents reflected four basic inter
      related needs and rights including the need and right: to be given a voice, to be
      informed and consulted, to be protected from harm, and for competent and
      efficient service provision. Study findings provided little support to the view
      that the medico-legal examination or the adversarial nature of legal proceedings
      are likely to be experienced as particularly distressing or traumatising for the
      child. CONCLUSIONS: Study findings indicate that the professional services
      provided to some child rape survivors fail to adequately address the child's
      basic needs and rights, with there being an associated need for improved codes of
      practice designed to better serve the interests of child rape survivors.

PMID- 25859893
TI  - The use and trends of information and communication technology (ICT) during
      middle childhood.
AB  - OBJECTIVE: Information and communication technologies (ICT) have become an
      integral part of people's lives. Trends suggest that the age when technology is
      used for the first time is rapidly decreasing and that children are exposed to
      ICT daily. However, the focus of the existing research has been on adolescents,
      and there is a dearth of knowledge about the use of ICT amongst children in
      middle childhood in South Africa. The objective of this study was to address this
      issue. METHOD: The research participants included 12 children aged between 6 and
      12 years old from two private schools (a boys' school and a girls' school) in the
      Gauteng region. A phenomenological approach was used to explore the use and
      trends of ICT among this age group. A semi-structured interview approach was
      employed for the data collection and each interview was tape-recorded and
      transcribed by the researcher. The Interpretative Phenomenological Analysis was
      used to analyse and interpret the data collected. RESULTS: Various themes were
      identified. While all the participants had been exposed to and used ICT, a clear
      developmental trend was observed: not only were younger children less
      sophisticated users of ICT, but they were also less informed about the dangers of
      ICT usage. The participants were generally not supervised but some rules were
      implemented by the parents. Although the children did not experience cyber
      bullying, they did report exposure to pornography. CONCLUSION: The results
      suggest various implications for developmental trends and protection of children.

PMID- 25859894
TI  - An exploratory study of psychological and developmental issues facing HIV and
      AIDS affected adolescents living in a residential care facility.
AB  - OBJECTIVE: This article explores the psychological issues experienced by
      adolescents affected by HIV and living in a residential care facility. METHOD:
      This was a multi-method, exploratory study. Data were collected through one focus
      group discussion with adolescents at the residential care facility, individual
      interviews with caregivers and ethnographic observation. Data were obtained from
      a residential care facility for HIV affected and infected children and mothers in
      Gauteng. RESULTS: Findings suggest that for adolescents in this study, living in
      a residential care facility offered both opportunities and challenges.
      Adolescents at the facility enjoyed material and, to some extent, emotional
      support. Association with a facility known as a HIV and AIDS care facility,
      however, had a negative impact on the adolescents. Additionally, the lack of
      significant attachment figures, asserting their independence and challenging the
      authority and the expectations of the facility appeared to be significant
      developmental challenges. Adolescents reported experiencing a range of emotional
      and psychological problems, some of which were present before they arrived at the
      facility. CONCLUSION: Living in a care facility can be both a protective and a
      risk factor; additional studies on the availability and the impact of alternate
      forms of care are suggested.

PMID- 25859890
TI  - Indications and Effects of Plasma Transfusions in Critically Ill Children.
AB  - RATIONALE: Plasma transfusions are frequently prescribed for critically ill
      children, although their indications lack a strong evidence base. Plasma
      transfusions are largely driven by physician conceptions of need, and these are
      poorly documented in pediatric intensive care patients. OBJECTIVES: To identify
      patient characteristics and to characterize indications leading to plasma
      transfusions in critically ill children, and to assess the effect of plasma
      transfusions on coagulation tests. METHODS: Point-prevalence study in 101
      pediatric intensive care units in 21 countries, on 6 predefined weeks. All
      critically ill children admitted to a participating unit were included if they
      received at least one plasma transfusion. MEASUREMENTS AND MAIN RESULTS: During
      the 6 study weeks, 13,192 children were eligible. Among these, 443 (3.4%)
      received at least one plasma transfusion and were included. The primary
      indications for plasma transfusion were critical bleeding in 22.3%, minor
      bleeding in 21.2%, planned surgery or procedure in 11.7%, and high risk of
      postoperative bleeding in 10.6%. No bleeding or planned procedures were reported
      in 34.1%. Before plasma transfusion, the median international normalized ratio
      (INR) and activated partial thromboplastin time (aPTT) values were 1.5 and 48,
      respectively. After plasma transfusion, the median INR and aPTT changes were -0.2
      and -5, respectively. Plasma transfusion significantly improved INR only in
      patients with a baseline INR greater than 2.5. CONCLUSIONS: One-third of
      transfused patients were not bleeding and had no planned procedure. In addition,
      in most patients, coagulation tests are not sensitive to increases in coagulation
      factors resulting from plasma transfusion. Studies assessing appropriate plasma
      transfusion strategies are urgently needed.

PMID- 25859895
TI  - Prevalence of enuresis in a community sample of children and adolescents referred
      for outpatient clinical psychological evaluation: Psychiatric comorbidities and
      association with intellectual functioning.
AB  - Research suggests a higher prevalence of coexisting behavioural disorders,
      particularly Attention-Deficit Hyperactivity Disorder (ADHD), among children with
      enuresis in comparison to the general population. Studies generally have
      consisted of participants attending general paediatric medical clinics as opposed
      to facilities specialising in the treatment of psychiatric disorders. This
      descriptive investigation examined the frequency of enuresis and its psychiatric
      comorbidities among 363 children and adolescents referred for outpatient clinical
      psychological evaluation during a 12-month period. Results revealed that 16% of
      participants met diagnostic criteria for enuresis and that of these 98% had at
      least one comorbid psychiatric disorder. Mood disorders were the most common
      coexisting diagnoses, followed by ADHD and Oppositional Defiant Disorder. No
      association was found between a diagnosis of enuresis and participant
      intelligence. Implications for mental health providers are discussed. 

PMID- 25859896
TI  - The shaking woman or a history of my nerves.
AB  - The shaking woman or a history of my nerves Siri Hustvedt 2010, Sceptre, London
      ISBN 978-0-340-99876-2. 

PMID- 25859897
TI  - Therapy with young men: 16-24 year olds in treatment.
AB  - Therapy with young men: 16-24 year olds in treatment Dave Verhaagen 2010,
      Routledge, Hove, East Sussex, UK; New York, New York, USA 217 pages Paperback,
      ISBN: 978-0-415-80447-9, ZAR 385.95 Hardback, ISBN: 978-0-415-80446-2. 

PMID- 25859898
TI  - The fighter.

PMID- 25859899
TI  - Journal abstracts from current research in the field of child and adolescent
      mental health.
AB  - Gonzales NA, Coxe S, Roosa MW, White RMB, Knight GP, Zeiders KH and Saenz D
      (2011) Economic hardship, neighborhood context, and parenting: Prospective
      effects on Mexican-American adolescent's mental health. American Journal of
      Community Psychology 47(1-2): 98-113 O'Kane D (2011) A phenomenological study of
      child and adolescent mental health consultation in primary care. Journal of
      Psychiatric and Mental Health Nursing 18(2): 185-188 Sentse M, Ormel J, Veenstra
      R, Verhulst FC and Oldehinkel AJ (2011) Child temperament moderates the impact of
      parental separation on adolescent mental health: The trails study. Journal of
      Family Psychology 25(1): 97-106 Leo RJ, Srinivasan SP and Parekh S (2011) The
      role of the mental health practitioner in the assessment and treatment of child
      and adolescent chronic pain. Child and Adolescent Mental Health 16(1): 2-8 James
      AC, Winmill L, Anderson C and Alfoadari K (2011) A preliminary study of an
      extension of a community dialectic behaviour therapy (DBT) programme to
      adolescents in the looked after care system. Child and Adolescent Mental Health
      16(1): 9-13 Flouri E, Hickey J, Mavroveli S and Hurry J (2011) Adversity,
      emotional arousal, and problem behaviour in adolescence: The role of non-verbal
      cognitive ability as a resilience promoting factor. Child and Adolescent Mental
      Health 16(1): 22-29 Paradis AD, Giaconia RM, Reinherz HZ, Beardslee WR, Ward KE
      and Fitzmaurice GM (2011) Adolescent family factors promoting healthy adult
      functioning: A longitudinal community study. Child and Adolescent Mental Health
      16(1): 30-37 Webster-Stratton C, Rinaldi J and Reid JM (2011) Long-term outcomes
      of Incredible Years parenting program: Predictors of adolescent adjustment. Child
      and Adolescent Mental Health 16(1): 38-46 Baruch G, Vrouva I and Wells C (2011)
      Outcome findings from a parent training programme for young people with conduct
      problems. Child and Adolescent Mental Health 16(1): 47-54 Davis Kenaley BL and
      Williams NJ (2011) A preliminary evaluation: Demographic and clinical profiles
      and changes in functioning in children receiving psychosocial rehabilitation.
      Children and Youth Services Review 33(2): 301-307. 

PMID- 25859902
TI  - Exploring Support for 100% College Tobacco-Free Policies and Tobacco-Free
      Campuses Among College Tobacco Users.
AB  - BACKGROUND: Tobacco-free campus policy is identified as an effective means to
      address tobacco use on college campuses; however, the prevalence of tobacco-free
      policies (TFPs) in the United States remains low. This study explores college
      tobacco users' support for a university's TFP and tobacco-free campuses (TFCs) in
      general. METHODS: A standardized and structured questionnaire was administered to
      790 college tobacco users recruited in a university located in a tobacco-growing
      region of the United States, during April-May 2011, to collect information on
      support for TFPs and TFCs and sociodemographic-political characteristics.
      Descriptive and multivariable logistic regression analyses were conducted to
      identify key factors associated with support for TFPs and TFCs. RESULTS:
      Approximately 2 of 5 tobacco users favored TFPs and TFCs. Multivariable logistic
      regression models showed that demographic factors were mostly not significantly
      associated with attitudes of the college tobacco users. Instead, while knowledge
      about harmful effects of exposure to secondhand tobacco smoke significantly
      increased support for both TFPs and TFCs, parental and peer smoking and exposure
      to tobacco industry promotions significantly decreased the likelihoods of support
      compared with respective referent groups. CONCLUSION: Study findings suggest that
      campus advocacy and education campaigns for campus tobacco policies to pay
      attention to tobacco use behavior of familial relations, tobacco industry
      activities, and other political determinants of tobacco users' attitudes. Thus,
      this study should inform national initiatives to promote TFPs nationwide such as
      the Tobacco-Free College Campus Initiative.

PMID- 25859901
TI  - Uses of NHANES Biomarker Data for Chemical Risk Assessment: Trends, Challenges,
      and Opportunities.
AB  - BACKGROUND: Each year, the U.S. NHANES measures hundreds of chemical biomarkers
      in samples from thousands of study participants. These biomarker measurements are
      used to establish population reference ranges, track exposure trends, identify
      population subsets with elevated exposures, and prioritize research needs. There
      is now interest in further utilizing the NHANES data to inform chemical risk
      assessments. OBJECTIVES: This article highlights a) the extent to which U.S.
      NHANES chemical biomarker data have been evaluated, b) groups of chemicals that
      have been studied, c) data analysis approaches and challenges, and d)
      opportunities for using these data to inform risk assessments. METHODS: A
      literature search (1999-2013) was performed to identify publications in which
      U.S. NHANES data were reported. Manual curation identified only the subset of
      publications that clearly utilized chemical biomarker data. This subset was
      evaluated for chemical groupings, data analysis approaches, and overall trends.
      RESULTS: A small percentage of the sampled NHANES-related publications reported
      on chemical biomarkers (8% yearly average). Of 11 chemical groups,
      metals/metalloids were most frequently evaluated (49%), followed by pesticides
      (9%) and environmental phenols (7%). Studies of multiple chemical groups were
      also common (8%). Publications linking chemical biomarkers to health metrics have
      increased dramatically in recent years. New studies are addressing challenges
      related to NHANES data interpretation in health risk contexts. CONCLUSIONS: This
      article demonstrates growing use of NHANES chemical biomarker data in studies
      that can impact risk assessments. Best practices for analysis and interpretation
      must be defined and adopted to allow the full potential of NHANES to be realized.

PMID- 25859903
TI  - Improving multiple sequence alignment by using better guide trees.
AB  - Progressive sequence alignment is one of the most commonly used method for
      multiple sequence alignment. Roughly speaking, the method first builds a guide
      tree, and then aligns the sequences progressively according to the topology of
      the tree. It is believed that guide trees are very important to progressive
      alignment; a better guide tree will give an alignment with higher accuracy.
      Recently, we have proposed an adaptive method for constructing guide trees. This
      paper studies the quality of the guide trees constructed by such method. Our
      study showed that our adaptive method can be used to improve the accuracy of many
      different progressive MSA tools. In fact, we give evidences showing that the
      guide trees constructed by the adaptive method are among the best. 

PMID- 25859905
TI  - How long does incisional pain last: early life vulnerability could make it last a
      lifetime.

PMID- 25859904
TI  - Targeting p38 Mitogen-activated Protein Kinase to Reduce the Impact of Neonatal
      Microglial Priming on Incision-induced Hyperalgesia in the Adult Rat.
AB  - BACKGROUND: Neonatal surgical injury triggers developmentally regulated long-term
      changes that include enhanced hyperalgesia and spinal microglial reactivity after
      reinjury. To further evaluate priming of response by neonatal hindpaw incision,
      the authors investigated the functional role of spinal microglial p38 mitogen
      activated protein kinase after reincision in adult rodents. METHODS: Plantar
      hindpaw incision was performed in anesthetized adult rats, with or without
      previous incision on postnatal day 3. Numbers and distribution of phosphorylated
      p38 (1, 3, 24 h) and phosphorylated extracellular signal-regulated kinase (15
      min, 24 h) immunoreactive cells in the lumbar dorsal horn were compared after
      adult or neonatal plus adult incision. Withdrawal thresholds evaluated reversal
      of incision-induced hyperalgesia by p38 inhibition with intrathecal SB203850.
      RESULTS: Neonatal injury significantly increased phosphorylated-p38 expression 3
      h after adult incision (55 +/- 4 vs. 35 +/- 4 cells per section, mean +/- SEM, n
      = 6 to 7, P < 0.01). Increased expression was restricted to microglia, maintained
      across lumbar segments, and also apparent at 1 and 24 h. Preincision intrathecal
      SB203850 prevented the enhanced mechanical hyperalgesia in adults with previous
      neonatal injury and was effective at a lower dose (0.2 vs. 1 mg/kg, n = 8, P <
      0.05) and for a longer duration (10 vs. 3 days). Lumbar neuronal phosphorylated
      extracellular signal-regulated kinase expression reflected the distribution of
      hindpaw primary afferents, but was not significantly altered by previous
      incision. CONCLUSIONS: Neonatal incision primes spinal neuroglial signaling, and
      reincision in adult rats unmasks centrally mediated increases in functional
      microglial reactivity and persistent hyperalgesia. After early life injury, p38
      inhibitors may have specific benefit as part of multimodal analgesic regimes to
      reduce the risk of persistent postsurgical pain.

PMID- 25859906
TI  - Preexisting cognitive impairment is associated with postoperative cognitive
      dysfunction after hip joint replacement surgery.
AB  - BACKGROUND: This study investigated the prevalence of cognitive impairment in
      elderly noncardiac surgery patients and any association between preoperative
      cognitive impairment and postoperative cognitive dysfunction (POCD).
      Additionally, the incidence of cognitive decline at 12 months after surgery was
      identified. METHODS: Three hundred patients for hip joint replacement and 51
      nonsurgical controls aged 60 yr or older were studied in a prospective
      observational clinical trial. All study participants and controls completed a
      battery of eight neuropsychological tests before surgery and at 7 days, 3 months,
      and 12 months afterwards. Preoperative cognitive status was assessed using
      preexisting cognitive impairment (PreCI) defined as a decline of at least 2 SD on
      two or more of seven neuropsychological tests compared to population norms. POCD
      and cognitive decline were assessed using the reliable change index utilizing the
      results of the control group. RESULTS: PreCI was classified in 96 of 300 (32%)
      patients (95% CI, 23 to 43%). After surgery, 49 of 286 (17%) patients (95% CI, 13
      to 22%) and 27 of 284 (10%) patients (95% CI, 6 to 13%) demonstrated POCD at 7
      days and 3 months, respectively, while 7 of 271 (3%) patients (95% CI, 1 to 4%)
      demonstrated cognitive decline at 12 months. Patients with PreCI had a
      significantly increased incidence of POCD at 7 days and 3 months and cognitive
      decline at 12 months. CONCLUSIONS: Patients with PreCI have an increased
      incidence of POCD and cognitive decline. PreCI is a good predictor of subsequent
      POCD and cognitive decline. The incidence of cognitive decline after 12 months in
      this group of patients is low.

PMID- 25859907
TI  - Highly torquoselective electrocyclizations and competing 1,7-hydrogen shifts of 1
      azatrienes with silyl substitution at the allylic carbon.
AB  - Highly torquoselective electrocyclizations of chiral 1-azatrienes are described.
      These 1-azatrienes contain an allylic stereocenter that is substituted with a
      silyl group and are derived in situ from condensation of gamma-silyl-substituted
      enals with vinylogous amides. The ensuing stereoselective ring closures are part
      of a tandem sequence that constitutes an aza-[3 + 3] annulation method for
      constructing 1,2-dihydropyridines. Several mechanisms for the formal 1,7-hydrogen
      shift of these 1-azatrienes were evaluated computationally. 

PMID- 25859908
TI  - The Population Burden of Chronic Symptoms that Substantially Predate the
      Diagnosis of a Life-Limiting Illness.
AB  - Many people in our communities live with symptoms for years or decades, something
      of relevance to hospice/palliative care clinicians and researchers. The
      proportion of people in the community at large who have a chronic symptom is
      likely to approximate the proportion of people referred to hospice/palliative
      care services with that same chronic symptom that pre-dates their life-limiting
      illness. Such patients may have different responsiveness to, and expectations
      from, symptomatic therapies, thus requiring more advanced approaches to symptom
      control. For researchers evaluating the impact of hospice/palliative care
      services, failing to account for people with long-term refractory symptoms pre
      dating their life-limiting illness may systematically underestimate services'
      benefits. Observational symptom prevalence studies reported in hospice/palliative
      care to date have not accounted for people with long-term refractory symptoms,
      potentially systematically overestimating symptoms attributed to life-limiting
      illnesses. Cross-sectional community prevalence rates of key chronic refractory
      symptoms largely unrelated to their life-limiting illness reflect the likely
      prevalence on referral to hospice/palliative care: fatigue (up to 35%); pain (12%
      31%); pain with neuropathic characteristics (9%); constipation (2%-29%); dyspnea
      (4%-9%); cognitive impairment (>10% of people >65 years old; >30% of people >85
      years old); anxiety (4%); and depression (lifetime incidence 2%-15%; one year
      prevalence 3%). Prospective research is needed to establish (1) the prevalence
      and severity of chronic symptoms that pre-date the diagnosis of a life-limiting
      illness in people referred to hospice/palliative care services, comparing this to
      whole-of-population estimates; and (2) whether this group is disproportionately
      represented in people with refractory symptoms. 

PMID- 25859909
TI  - Experimental and Theoretical Study on the OH-Reaction Kinetics and Photochemistry
      of Acetyl Fluoride (CH3C(O)F), an Atmospheric Degradation Intermediate of HFC-161
      (C2H5F).
AB  - The direct reaction kinetic method of low pressure fast discharge flow (DF) with
      resonance fluorescence monitoring of OH (RF) has been applied to determine rate
      coefficients for the overall reactions OH + C2H5F (EtF) (1) and OH + CH3C(O)F
      (AcF) (2). Acetyl fluoride reacts slowly with the hydroxyl radical, the rate
      coefficient at laboratory temperature is k2(300 K) = (0.74 +/- 0.05) * 10(-14)
      cm(3) molecule(-1) s(-1) (given with 2sigma statistical uncertainty). The
      temperature dependence of the reaction does not obey the Arrhenius law and it is
      described well by the two-exponential rate expression of k2(300-410 K) = 3.60 *
      10(-3) exp(-10500/T) + 1.56 * 10(-13) exp(-910/T) cm(3) molecule(-1) s(-1). The
      rate coefficient of k1 = (1.90 +/- 0.19) * 10(-13) cm(3) molecule(-1) s(-1) has
      been determined for the EtF-reaction at room temperature (T = 298 K). Microscopic
      mechanisms for the OH + CH3C(O)F reaction have also been studied theoretically
      using the ab initio CBS-QB3 and G4 methods. Variational transition state theory
      was employed to obtain rate coefficients for the OH + CH3C(O)F reaction as a
      function of temperature on the basis of the ab initio data. The calculated rate
      coefficients are in good agreement with the experimental data. It is revealed
      that the reaction takes place predominantly via the indirect H-abstraction
      mechanism involving H-bonded prereactive complexes and forming the nascent
      products of H2O and the CH2CFO radical. The non-Arrhenius behavior of the rate
      coefficient at temperatures below 500 K is ascribed to the significant tunneling
      effect of the in-the-plane H-abstraction dynamic bottleneck. The production of
      FC(O)OH + CH3 via the addition/elimination mechanism is hardly competitive due to
      the significant barriers along the reaction routes. Photochemical experiments of
      AcF were performed at 248 nm by using exciplex lasers. The total
      photodissociation quantum yield for CH3C(O)F has been found significantly less
      than unity; among the primary photochemical processes, C-C bond cleavage is by
      far dominating compared with CO-elimination. The absorption spectrum of AcF has
      also been determined by displaying a strong blue shift compared with the spectra
      of aliphatic carbonyls. Consequences of the results on atmospheric chemistry have
      been discussed. 

PMID- 25859910
TI  - Evaluating adverse drug reactions among HAART patients in a resource-constrained
      province of South Africa.
AB  - The high prevalence of HIV in KwaZulu-Natal Province, South Africa, has greatly
      increased the demand for antiretroviral therapy (ART), resulting in an
      exponential increase in the number of patients initiated on highly active
      antiretroviral treatment (HAART). However, little information about adverse drug
      reactions in these patients was forthcoming from public health facilities in
      KwaZulu-Natal. A compulsory system of reporting adverse drug reactions was
      established among patients attending accredited ART sites, with minimal resource
      requirements. The study sought to evaluate the adverse drug reactions reported
      through the new compulsory system. A retrospective audit was performed on the
      reporting forms received during the first year of the new system, pertaining to
      all patients on HAART who had experienced an adverse drug reaction that resulted
      in a request for a change in antiretroviral (ARV) drug or regimen. The forms for
      documenting adverse drug reactions were completed by prescribers who would
      confirm the event or reaction by specifying the diagnosis as well as the relevant
      clinical and laboratory values. In total, 3 923 forms, submitted between 1 May
      2007 and 31 May 2008, were available for audit. Adverse drug reactions were
      documented in 78.7% of the reports and 74% of the patients that presented with an
      adverse event were females. Of the forms recording a serious adverse drug
      reaction, 84.7% pertained to patients taking the three-drug combination
      stavudine, lamivudine and either efavirenz or nevirapine. Of those reports,
      stavudine was implicated as the possible causative agent of an adverse drug
      reaction in 93% of the cases. In 73.6% of the total reports the proposed new
      regimen was zidovudine, lamivudine and efavirenz or nevirapine. The compulsory
      system of reporting greatly improved the reporting of adverse drug reactions
      associated with HAART among patients in the province. This system may be
      similarly implemented in other low-resourced settings to actively encourage the
      reporting of adverse drug reactions associated with ARV use. 

PMID- 25859911
TI  - Analysis of factors associated with failure to return for an HIV-test result in
      The Gambia.
AB  - Knowing one's HIV status is fundamental to the prevention and treatment of HIV
      and AIDS. However, HIV prevention is defeated if individuals who opt to be tested
      fail to return for their test result. Despite the burden of HIV and AIDS in sub
      Saharan Africa, regional studies on failure to return (FTR) for an HIV-test
      result are lacking. We investigated the factors associated with FTR in The
      Gambia, West Africa. FTR was analysed for 1 755 persons who attended an
      outpatient clinic during 2000 to 2009. Overall, the proportion of FTR was 30%.
      Logistic regression showed that FTR was significantly higher among males,
      individuals whose nationality was not Gambian, individuals with a history of
      condom use, and individuals who resided in an urban area. Persons who were
      younger than age 18 years and persons who had received some formal education were
      more likely to not return for the HIV-test result than were persons aged 40 years
      or older and persons without formal schooling. The results provide evidence for
      the need for appropriate strategies to increase the receipt of HIV-test results
      among people in the general population and among certain group profiles. 

PMID- 25859912
TI  - A framework to expand public services to children with biomedical healthcare
      needs related to HIV in the Free State, South Africa.
AB  - The study undertook the development of a framework for expanding the public
      services available to children with biomedical healthcare needs related to HIV in
      South Africa. The study consisted of various component projects which were
      depicted as phases. The first phase was a descriptive quantitative analysis of
      healthcare services for children exposed to or infected by HIV, as rendered by
      the public health sector in the Free State Province. The second stage was
      informed by health policy research: a nominal group technique with stakeholders
      was used to identify strategies for expanding the healthcare services available
      to these children. The third phase consisted of workshops with stakeholders in
      order to devise and validate a framework for the expansion. The theory of change
      logic model served as the theoretical underpinning of the draft framework.
      Triangulated data from the literature and the preceding two phases of the study
      provided the empirical foundation. The problem identified was that of fragmented
      care delivered to children exposed to or infected with HIV, due to the 'over
      verticalization' of programmes. A workshop was held during which the desired
      results, the possible factors that could influence the results, as well as the
      suggested strategies to expand and integrate the public services available to HIV
      affected children were confirmed. Thus the framework was finalised during the
      validation workshop by the researchers in collaboration with the stakeholders. 

PMID- 25859914
TI  - AIDS fatigue and university students' talk about HIV risk.
AB  - Drawing on a qualitative study that included 20 focus group discussions with male
      and female students at an urban-based university in South Africa, this article
      reports on perceptions, attitudes and reported behaviour with respect to HIV and
      AIDS and safer sex in the campus setting, with an aim to better understand how
      young people are responding to the challenges of HIV and AIDS in contemporary
      South Africa. The findings demonstrate the gap between reported HIV-prevention
      knowledge and safer-sex practices among a group of young and educated South
      Africans. Although the participants reported that students were knowledgeable
      about HIV and had easy access to condoms on campus, a range of factors mediated
      their capacity to apply this knowledge to safer-sex practices. Besides the usual
      set of complex social-cultural dynamics, including normative gender roles and
      power inequalities between men and women, socioeconomic challenges, and
      differences in age and status between sexual partners, the findings reveal
      substantial denial, stigma and HIV/AIDS 'fatigue.' The findings point to the
      importance of seeking creative ways to impart HIV-prevention and safer-sex
      messages that are not explicitly referent to HIV but link rather with broader
      issues concerning relationships, lifestyle and identity, and hence are responsive
      to the particular cultural context of university campuses. 

PMID- 25859913
TI  - Perceptions of HIV, AIDS and tuberculosis among patients on antiretroviral
      therapy in Bulawayo, Zimbabwe: implications for the provision of HIV and TB care
      services.
AB  - The objectives of the research were to explore perceptions of HIV, AIDS and
      tuberculosis (TB) among individuals enrolled in antiretroviral therapy (ART) at
      two municipal clinics in Bulawayo, Zimbabwe, and to assess the implications of
      these perceptions on the provision of HIV and TB care services. Data were
      collected using the freelist technique to elicit the elements of a cultural
      domain as well as open-ended interviews with ART clients, conducted during June
      and July 2009. Participants were recruited through non-probability convenience
      sampling. The freelist data were analysed using multidimensional scaling and
      hierarchical clustering, and the interview data were analysed using the grounded
      theory method. The results suggest that: 1) the participants had substantial
      knowledge about HIV, AIDS and TB; 2) the participants' perceptions of HIV, AIDS
      and TB constituted three distinct, though overlapping, cultural domains; 3)
      because of the availability of ART and TB treatment, a diagnosis of HIV infection
      or TB alone was generally perceived with hope that one would be able to live a
      normal life, while AIDS illness or TB/HIV coinfection were associated with
      notions of death and despair; and, 4) such perceptions may negatively impact the
      uptake of testing for HIV and TB, and thereby contribute to delayed start of the
      respective treatment. Health messages should build on these meanings which have
      the potential to either enhance or compromise available health programmes and
      their use by people living with HIV or TB. 

PMID- 25859915
TI  - A narrative review of research on the effects of physical activity on people
      living with HIV and opportunities for health promotion in disadvantaged settings.
AB  - The article explores different types and effects of physical activity for people
      living with HIV. Considering the lack of studies done in African contexts and the
      disparity between research settings and natural settings, a narrative review of
      the literature was conducted and contextualised to South Africa. Various
      physical, psychological and social-cultural constraints impair the wellbeing of
      people living with HIV, in part by restricting their participation in physical
      activities. Apart from the well-studied immediate physiological benefits on
      health, we argue that physical-sportive group activities, such as sport or
      recreational games, can improve psychosocial factors and generate holistic health
      effects for people living with HIV. Group-activity effects could improve
      individuals' motivation and adherence to participating in physical activities,
      provided that positive interaction and non-stigmatisation are guaranteed.
      However, most studies in this field have been limited to the benefits of aerobic
      exercise and resistance training. There has been little research on the types and
      different effects of physical activity and adherence to physical activity of
      people living with HIV in African contexts. Based on an analysis of the different
      types and effects, we suggest opportunities for and challenges to implementing
      physical activities for people living with HIV, especially in disadvantaged
      settings, and also identify gaps in the research to date. 

PMID- 25859916
TI  - Children as caregivers of older relatives living with HIV and AIDS in Nyang'oma
      division of western Kenya.
AB  - There is growing debate about the situations of children who care for a relative
      with HIV-related illness, especially in developing countries with high HIV
      prevalence. In particular, there is inadequate information on the long-term
      consequences of children taking on this caregiving role. The article reanalyses
      data collected between January and November 2006 in a rural setting in western
      Kenya where 19 children caring for a total of 15 people living with HIV or AIDS
      (PLHIV) participated. Data were collected through in-depth interviews,
      participant observation, focus group discussions and narratives. The findings
      show that children regularly become involved in caregiving due to lack of a
      responsible adult to perform the role, which may be as a result of HIV stigma and
      rejection of the care recipient by extended family members and neighbours or
      because of cultural barriers. Fulfilling the responsibilities of caregiving had
      profound repercussions for the children's lives, including psychological
      distress, physical burden, dropping out of school, participation in wage labour,
      and forced early marriage. Financial needs pushed some girls into transactional
      sexual relations, predisposing them to the risks of unwanted pregnancy or
      sexually transmitted infections. Since the children providing care for PLHIV are
      themselves vulnerable, we recommend that they should be targeted with support. 

PMID- 25859917
TI  - Understanding the agency of home-based care volunteers: establishing identity and
      negotiating space in AIDS-home-based care in rural KwaZulu-Natal, South Africa.
AB  - In traditional Zulu communities, caregiving is rooted in compassionate and
      hardworking personal identity precepts and the traditional identity expectations
      of women. Home-based-care volunteerism in the community represents the
      performance of this identity. Data from a series of interviews with 15 home-based
      care volunteers (HBCVs), in a rural community in KwaZulu-Natal Province, South
      Africa, is used to illustrate how HBCVs promote the notion of women as paid home
      based caregivers, with a recognised space in the care and support system
      regarding HIV and AIDS. Home-based-care volunteering also represents the attempt
      by women to be seen, heard and recognised in the hope that it will lead to self
      improvement and the improvement of their families. Volunteer motivations vary
      from altruism, to volunteering as a means to be recognised and increasing the
      chances of self-improvement. We propose that home-based-care volunteering may be
      viewed as a form of agency in response to a lack of recognition, support and
      acknowledgement for AIDS caregivers and their patients. The continued lack of
      support for HBCVs over a long period undermines the work and the basis of the
      HBCVs' identity or the aspects of identity on which the motivation for the work
      is based. 

PMID- 25859918
TI  - Recent advances in the understanding of two-step nucleation of protein crystals.
AB  - The two-step mechanism of nucleation of crystals in solutions posits that the
      formation of crystal nuclei occurs within structures of extended lifetimes, in
      which the nucleating solute is at high concentration. The validity of this
      mechanism has been demonstrated for proteins, small-molecule organic and
      inorganic materials, colloids, and polymers. Due to large molecule sizes,
      proteins are an ideal system to study the details of this nucleation pathway, in
      particular the formation mechanisms of the nucleation precursors and the
      associated physico-chemical rules. The precursors of protein crystal nuclei are
      protein-rich clusters of sizes ~100 nm that contain 10,000-100,000 molecules and
      occupy less than 10(-3) of the total solution volume. Here we demonstrate, using
      oblique illumination microscopy, the liquid nature of the clusters of the protein
      lysozyme and reveal their inhomogeneous structure. We test a hypothesis put forth
      by theory that clusters primarily consist of transient protein oligomers. For
      this, we explore how varying the strength of the Coulomb interaction affects the
      cluster characteristics. We find that the cluster's size is insensitive to
      variations of pH and ionic strength. In contrast, the addition of urea, a
      chaotropic agent that leads to protein unfolding, strongly decreases the cluster
      size. Shear stress, a known protein denaturant, induced by bubbling of the
      solutions with an inert gas, elicits a similar response. These observations
      support partial protein unfolding, followed by dimerization, as the mechanism of
      cluster formation. The amide hydrogen-deuterium exchange, monitored by nuclear
      magnetic resonance, highlights that lysozyme conformational flexibility is a
      condition for the formation of the protein-rich clusters and facilitates the
      nucleation of protein crystals.

PMID- 25859919
TI  - The effects of social capital and neighborhood characteristics on intimate
      partner violence: a consideration of social resources and risks.
AB  - Intimate partner violence (IPV) is a growing public health problem, and gaps
      exist in knowledge with respect to appropriate prevention and treatment
      strategies. A growing body of research evidence suggests that beyond individual
      factors (e.g., socio-economic status, psychological processes, substance abuse
      problems), neighborhood characteristics, such as neighborhood economic
      disadvantage, high crime rates, high unemployment and social disorder, are
      associated with increased risk for IPV. However, existing research in this area
      has focused primarily on risk factors inherent in neighborhoods, and has failed
      to adequately examine resources within social networks and neighborhoods that may
      buffer or prevent the occurrence of IPV. This study examines the effects of
      neighborhood characteristics, such as economic disadvantage and disorder, and
      individual and neighborhood resources, such as social capital, on IPV among a
      representative sample of 2412 residents of Toronto, Ontario, Canada. Using a
      population based sample of 2412 randomly selected Toronto adults with
      comprehensive neighborhood level data on a broad set of characteristics, we
      conducted multi-level modeling to examine the effects of individual- and
      neighborhood-level effects on IPV outcomes. We also examined protective factors
      through a comprehensive operationalization of the concept of social capital,
      involving neighborhood collective efficacy, community group participation, social
      network structure and social support. Findings show that residents who were
      involved in one or more community groups in the last 12 months and had high
      perceived neighborhood problems were more likely to have experienced physical
      IPV. Residents who had high perceived social support and low perceived
      neighborhood problems were less likely to experience non-physical IPV. These
      relationships did not differ by neighborhood income or gender. Findings suggest
      interesting contextual effects of social capital on IPV. Consistent with previous
      research, higher levels of perceived neighborhood problems can reflect
      disadvantaged environments that are more challenged in promoting health and
      regulating disorder, and can create stressors in which IPV is more likely to
      occur. Such analyses will be helpful to further understanding of the complex,
      multi-level pathways related to IPV and to inform the development of effective
      programs and policies with which to address and prevent this serious public
      health issue.

PMID- 25859921
TI  - Correction to Protocatechuic Acid Inhibits Oleic Acid-Induced Vascular Smooth
      Muscle Cell Proliferation through Activation of AMP-Activated Protein Kinase and
      Cell Cycle Arrest in G0/G1 Phase.

PMID- 25859920
TI  - Get the message: targeting beliefs to develop risk reduction intervention
      messages for African American adolescents.
AB  - Risk reduction interventions that promote condom use, a vital component of most
      HIV prevention interventions, have been successful in increasing condom use among
      African American adolescents. Understanding theoretical components that lead to
      behavior change and selecting relevant risk reduction messages remain important
      considerations for targeting new interventions and tailoring existing
      interventions. The present study sought to (1) identify the most important
      theoretical determinants of condom use intention in African American adolescent
      males and females, separately, using the integrative model of behavior
      prediction, and (2) identify underlying beliefs within the determinants that were
      good candidates for message development in similar interventions. Using 446
      African American adolescents, multi-group SEM indicated that the gender-specific
      IM exhibited a better fit than the overall model. Specifically, the IM had a
      stronger capacity for predicting condom use intention and condom use behavior for
      adolescent boys. Using a specific criteria for message selection, specific condom
      use beliefs were discussed as potential candidate messages for both African
      American males and females. 

PMID- 25859922
TI  - PZT-like structural phase transitions in the BiFeO3-KNbO3 solid solution.
AB  - Despite the high prominence of the perovskites BiFeO(3) and KNbO(3) the solid
      solution between the two has received little attention. We report a detailed
      neutron and synchrotron X-ray powder diffraction, and Raman spectroscopy study
      which demonstrates an R3c->P4mm->Amm2 series of structural phase transitions
      similar to that exhibited by the PbZrO(3)-PbTiO(3) solid solution.

PMID- 25859923
TI  - Metabotropic glutamate receptor 1 disrupts mammary acinar architecture and
      initiates malignant transformation of mammary epithelial cells.
AB  - Metabotropic glutamate receptor 1 (mGluR1/Grm1) is a member of the G-protein
      coupled receptor superfamily, which was once thought to only participate in
      synaptic transmission and neuronal excitability, but has more recently been
      implicated in non-neuronal tissue functions. We previously described the
      oncogenic properties of Grm1 in cultured melanocytes in vitro and in spontaneous
      melanoma development with 100 % penetrance in vivo. Aberrant mGluR1 expression
      was detected in 60-80 % of human melanoma cell lines and biopsy samples. As most
      human cancers are of epithelial origin, we utilized immortalized mouse mammary
      epithelial cells (iMMECs) as a model system to study the transformative
      properties of Grm1. We introduced Grm1 into iMMECs and isolated several stable
      mGluR1-expressing clones. Phenotypic alterations in mammary acinar architecture
      were assessed using three-dimensional morphogenesis assays. We found that mGluR1
      expressing iMMECs exhibited delayed lumen formation in association with decreased
      central acinar cell death, disrupted cell polarity, and a dramatic increase in
      the activation of the mitogen-activated protein kinase pathway. Orthotopic
      implantation of mGluR1-expressing iMMEC clones into mammary fat pads of
      immunodeficient nude mice resulted in mammary tumor formation in vivo. Persistent
      mGluR1 expression was required for the maintenance of the tumorigenic phenotypes
      in vitro and in vivo, as demonstrated by an inducible Grm1-silencing RNA system.
      Furthermore, mGluR1 was found be expressed in human breast cancer cell lines and
      breast tumor biopsies. Elevated levels of extracellular glutamate were observed
      in mGluR1-expressing breast cancer cell lines and concurrent treatment of MCF7
      xenografts with glutamate release inhibitor, riluzole, and an AKT inhibitor led
      to suppression of tumor progression. Our results are likely relevant to human
      breast cancer, highlighting a putative role of mGluR1 in the pathophysiology of
      breast cancer and the potential of mGluR1 as a novel therapeutic target. 

PMID- 25859924
TI  - Oncotype Dx assay and breast cancer in the United States: usage and concordance
      with chemotherapy.
AB  - The 21-gene recurrence score (RS) assay (Oncotype DXTM) predicts the likelihood
      of breast cancer recurrence and chemotherapy responsiveness. The aims of this
      study were to describe temporal trends in assay usage, to investigate factors
      associated with the receipt of the assay and to determine how the assay is
      associated with treatment decisions. Random samples of stage I-II female breast
      cancer patients diagnosed in 2004, 2005 and 2010 as reported to the National
      Cancer Institute's Surveillance Epidemiology and End Results program were
      included. Among women diagnosed in 2010 with estrogen receptor positive (ER+),
      lymph node-negative (LN-) tumors, factors associated with receipt of the assay
      were identified and the likelihood of chemotherapy by RS was estimated. Assay
      usage increased over time (ER+/LN-:8.0-27.0 %, p < 0.01; ER+/LN+: 2.0-15.7 %, p =
      0.09; ER-: 0.2-1.7 %, p < 0.01) from 2005 to 2010. Receipt of the assay was
      associated with younger age, lower area income and tumor characteristics. Among
      women in the low (RS < 18) and high risk (RS > 30) categories, 3.3 and 95.9 %
      received chemotherapy, respectively. Within the intermediate risk group the
      receipt of chemotherapy varied: 12.8 % (RS: 18-19), 35.0 % (RS: 20-23) and 84.0 %
      (RS: 24-30). During the study years, assay usage increased among women for whom
      the assay is and is not guideline recommended. Factors such as insurance and
      race/ethnicity do not appear to be associated with the receipt of the assay. The
      RS, as determined broadly via three categories and within the intermediate risk
      group, does appear to influence chemotherapy decisions.

PMID- 25859925
TI  - Parasitic diversity found in coprolites of camelids during the Holocene.
AB  - Knowledge of parasitic infections to which fauna was exposed in the past provides
      information on the geographical origin of some parasites, on the possible
      dispersal routes and for archaeological fauna on the potential zoonotic risk that
      human and animal populations could be exposed. The aim of the present study was
      to examine the gastrointestinal parasite present in camelid coprolites collected
      from the archaeological site Cerro Casa de Piedra, cave 7 (CCP7), Patagonia,
      Argentina. Coprolites were collected from different stratified sequences dating
      from the Pleistocene-Holocene transition to the late Holocene.
      Paleoparasitological examination revealed the presence of eggs of
      Trichostrongylidae attributed to Lamanema chavezi or Nematodirus lamae, eggs of
      three unidentified capillariids, Strongylus-type eggs and oocysts of Eimeria
      macusaniensis. These parasites affected camelids living in the studied area since
      the Pleistocene-Holocene transition, about 10,000 years ago. Gastrointestinal
      parasite fauna of patagonian camelids did not vary significatively from
      Pleistocene-Holocene transition to late Holocene, although environmental
      conditions fluctuated greatly throughout this period, as indicative of the
      strength and the stability of these associations over time. In this study, the
      zoonotic and biogeography importance of parasites of camelids are also discussed.

PMID- 25859926
TI  - Characterization of Blastocystis species infection in humans and mantled howler
      monkeys, Alouatta palliata aequatorialis, living in close proximity to one
      another.
AB  - This study characterizes Blastocystis species infections in humans and mantled
      howler monkeys, Alouatta palliata aequatorialis, living in close proximity to one
      another in northwestern Ecuador. Blastocystis species were identified from 58 of
      96 (60.4 %) mantled howler monkey fecal samples, and 44 of 55 human fecal samples
      (81.5 %) by polymerase chain reaction. Using single-stranded conformation
      polymorphism, we were able to efficiently separate and sequence subtypes (STs)
      within mixed samples without the need for cloning. Blastocystis ST1, ST2, and ST3
      were found in people, and two individuals were infected with more than one
      subtype. All monkey samples were ST8. The lack of shared subtypes between humans
      and monkeys suggests that no Blastocystis transmission occurs between these
      species in spite of close proximity in some instances. Based on analysis of
      demographic data from a questionnaire given to human participants, individuals
      who boiled their water before consumption were significantly less likely to be
      infected with Blastocystis (44.4 %) compared to those who did not (93.8 %) (p =
      0.002). No other risk factors were significant, although hunters, females,
      individuals living in large families, and those living closer to forested habitat
      tended to have a higher proportion of Blastocystis infections. 

PMID- 25859927
TI  - Ultrastructure of antennal sensory organs of horse nasal-myiasis fly, Rhinoestrus
      purpureus (Diptera: Oestridae).
AB  - Rhinoestrus purpureus (Brauer, 1858) (Diptera: Oestridae) is an economically
      important parasite that can cause severe nasal myiasis in equids or even
      attacking humans. The antennae of R. purpureus were examined using stereoscopic
      microscopy and scanning electron microscopy. The general morphology was provided
      detailedly, together with distribution, type, size, and ultrastructure of
      antennal sensilla. All the three antennal segments, antennal scape, pedicel, and
      funiculus, are interspersed by microtrichiae. Only mechanoreceptors are detected
      on antennal scape and pedicel. On antennal funiculus, three types of sensilla
      were observed, including basiconic sensilla, coeloconic sensilla and clavate
      sensilla. Two features are characterized of this host-specific bot fly: (1)
      numerous sensory pits with branched basiconic sensilla on antennal funiculus and
      (2) the absence of trichoid sensilla. The function of these distinctive traits
      are discussed in association with the life history. We suggest that more sensory
      pits with branched sensilla could increase the sensitivity of olfactory system
      for host orientation, while the capability of pheromone identification might be
      reduced due to the absence of trichoid sensilla. Besides, we support both thermo-
      and chemo-functions of coeloconic sensilla. 

PMID- 25859929
TI  - [Proctology].

PMID- 25859928
TI  - [Skin cancer screening in Germany : The situation in 2014 with suggestions for
      the future].
AB  - Based on the skin cancer screening model of Germany a critical statement is
      presented about skin cancer epidemiology, the total body examination and time
      intervals. The number of skin cancer cases will increase and the number of
      dermatologists will probably decrease; thus a fundamental and pragmatic strategy
      is required for further education and planning to comply with the increased
      dermato-oncological demand of an aging population. Hereby dermoscopy should be a
      basic diagnostic tool for the early recognition of skin cancer and precursors as
      well as to avoid unnecessary excisions of benign skin lesions. The excision ratio
      between malignant and benign skin tumours should be optimized. 

PMID- 25859930
TI  - [HPV-induced anal lesions].
AB  - Human papillomavirus (HPV) infections belong to the most common sexually
      transmitted infections. To date, more than 200 completely classified HPV-types
      have been reported, and those belonging to the genus alpha predominantly infect
      the anogenital region. Condylomata acuminata are caused by the two low-risk types
      HPV6 and HPV11 in more than 90 % of cases. Treatment of genital warts might be
      either ablative (e.g. electrocautery, surgical excision, or laser therapy) or
      topical (e.g. podophyllotoxine, trichloroacetic acid, or imiquimod), and depends
      on the size, location, morphology and anatomical region. Recurrences after
      treatment are frequent. Therefore, combination therapies (e.g. topical and
      ablative) play an important role in daily routine. HIV-infected individuals,
      especially HIV-positive MSM, have a strongly increased risk for anal dysplasia
      and anal cancer. Condylomata acuminata and a large proportion of anal dysplasia
      and anal carcinoma are preventable by prophylactic HPV-vaccination.

PMID- 25859931
TI  - Tandem prenyltransferases catalyze isoprenoid elongation and complexity
      generation in biosynthesis of quinolone alkaloids.
AB  - Modification of natural products with prenyl groups and the ensuing oxidative
      transformations are important for introducing structural complexity and
      biological activities. Penigequinolones (1) are potent insecticidal alkaloids
      that contain a highly modified 10-carbon prenyl group. Here we reveal an
      iterative prenylation mechanism for installing the 10-carbon unit using two
      aromatic prenyltransferases (PenI and PenG) present in the gene cluster of 1 from
      Penicillium thymicola. The initial Friedel-Crafts alkylation is catalyzed by PenI
      to yield dimethylallyl quinolone 6. The five-carbon side chain is then
      dehydrogenated by a flavin-dependent monooxygenase to give aryl diene 9, which
      serves as the electron-rich substrate for a second alkylation with dimethylallyl
      diphosphate to yield stryrenyl product 10. The completed, oxidized 10-carbon
      prenyl group then undergoes further structural morphing to yield yaequinolone C
      (12), the immediate precursor of 1. Our studies have therefore uncovered an
      unprecedented prenyl chain extension mechanism in natural product biosynthesis. 

PMID- 25859932
TI  - MiR-206, a Cerebellum Enriched miRNA Is Downregulated in All Medulloblastoma
      Subgroups and Its Overexpression Is Necessary for Growth Inhibition of
      Medulloblastoma Cells.
AB  - Medulloblastoma is the most common and a highly malignant pediatric brain tumor
      located in the cerebellar region of the brain. Medulloblastomas have recently
      been shown to consist of four distinct molecular subgroups, viz., WNT, SHH, group
      3, and group 4. MiR-206, a miRNA first identified as a myomiR due to its enriched
      expression in skeletal muscle was found to be expressed specifically in the
      cerebellum, the site of medulloblastoma occurrence. MiR-206 expression was found
      to be downregulated in medulloblastomas belonging to all the four molecular
      subgroups as well as in established medulloblastoma cell lines. Further, the
      expression of murine homolog of miR-206 was also found to be downregulated in SHH
      subgroup medulloblastomas from the Smo (+/+) transgenic mice and the Ptch1 (+/-)
      knockout mice. MiR-206 downregulation in all the four medulloblastoma subgroups
      suggests tumor-suppressive role for miR-206 in medulloblastoma pathogenesis. The
      effect of miR-206 expression was analyzed in three established medulloblastoma
      cell lines, viz., Daoy, D425, and D283 belonging to distinct molecular subgroups.
      Restoration of miR-206 expression to the levels comparable to those in the normal
      cerebellum, however, was found to be insufficient to inhibit the growth of
      established medulloblastoma cell lines. OTX2, an oncogenic miR-206 target,
      overexpressed in all non-SHH medulloblastomas, is known to inhibit myogenic
      differentiation of medulloblastoma cells. Overexpression of miR-206 was necessary
      to downregulate OTX2 expression and inhibit growth of medulloblastoma cell lines.

PMID- 25859933
TI  - Microstructural White Matter Abnormalities and Cognitive Dysfunction in
      Subcortical Ischemic Vascular Disease: an Atlas-Based Diffusion Tensor Analysis
      Study.
AB  - Recent studies in subcortical ischemic vascular disease (SIVD) suggest the
      involvement of white matter (WM) abnormalities underlying the pathogenesis of
      cognitive function impairment. Here, we performed magnetic resonance diffusion
      tensor imaging (DTI) on detecting WM damage and to investigate the correlations
      between DTI measures and cognitive dysfunction in SIVD patients. Fifty right
      handed SIVD patients were recruited and divided into vascular cognitive
      impairment on dementia (VCIND) group and normal cognition (NC) group. Twenty-two
      VCIND patients and 28 NC patients underwent DTI scanning and neuropsychological
      assessment. Atlas-based analysis (ABA) was performed on each subject for
      extracting FA and MD measures from supratentorial tracts. Among VCIND, as
      compared to NC patients, decreased FA and increased MD were observed in all
      projection fibers (bilateral anterior, posterior limb, and retrolenticular part
      of internal capsule, anterior, superior, and posterior corona radiata and
      posterior thalamic radiation), association fibers (bilateral sagittal stratum,
      external capsule, cingulum, fornix, and stria terminalis, superior longitudinal
      fasciculus, superior fronto-occipital fasciculus, and uncinate fasciculus), and
      commissural fibers (genu, body, splenium, and bilateral tapetum of corpus
      callosum). Furthermore, we also found that MoCA scores correlated with DTI values
      in all supratentorial WM tracts. The results suggested that SIVD patients
      demonstrated abnormal WM connectivity in all supratentorial regions. Moreover,
      the severity of damage in WM tracts correlated with cognitive dysfunction. 

PMID- 25859935
TI  - Genetic Variation of ApoE Gene in Ethnic Kashmiri Population and Its Association
      with Outcome After Traumatic Brain Injury.
AB  - The outcome from traumatic brain injury (TBI) is variable and only partly
      explained by known prognostic factors. Genetic factors may influence the brain's
      susceptibility to injury or capacity for repair and regeneration. ApoE has been
      implicated in modifying neurological outcome after TBI, although the mechanisms
      by which this occurs remain poorly defined. Apolipoprotein E is an apparently
      multifunctional protein involved in the response of the brain to injury and in
      subsequent repair processes. Several studies have shown that patients with APOE
      e4 have a poorer outcome after TBI. This study was aimed to analyse the genotypes
      of ApoE in Kashmiri population and to examine the association of APOE genotype
      with outcome after TBI. A total of 450 subjects (300 healthy controls and 150 TBI
      patients) were recruited for the study. Genotyping was done by PCR-restriction
      fragment length polymorphism (RFLP).Our study indicated Apoe3/e3 to be the most
      common genotype in this study group. The allele frequency of the Apo E gene in
      these study subjects was observed to be 0.07 for the e2 allele, 0.82 for the e3
      allele and 0.11 for the e4 allele. However, no association between the presence
      of APOe4 allele and outcome after head injury was observed in this study [p =
      0.92]. Thus, genotype containing the e4 allele (e4/e3 and e4/e4) was not
      associated with unfavourable outcome after TBI in Kashmiri population.

PMID- 25859934
TI  - Regulatory Mechanisms of Endoplasmic Reticulum Resident IP3 Receptors.
AB  - Dysregulated calcium signaling and accumulation of aberrant proteins causing
      endoplasmic reticulum stress are the early sign of intra-axonal pathological
      events in many neurodegenerative diseases, and apoptotic signaling is initiated
      when the stress goes beyond the maximum threshold level of endoplasmic reticulum.
      The fate of the cell to undergo apoptosis is controlled by Ca2(+) signaling and
      dynamics at the level of the endoplasmic reticulum. Endoplasmic reticulum
      resident inositol 1,4,5-trisphosphate receptors (IP3R) play a pivotal role in
      cell death signaling by mediating Ca2(+) flux from the endoplasmic reticulum into
      the cytosol and mitochondria. Hence, many prosurvival and prodeath signaling
      pathways and proteins affect Ca2(+) signaling by directly targeting IP3R
      channels, which can happen in an IP3R-isoform-dependent manner. Here, in this
      review, we summarize the regulatory mechanisms of inositol triphosphate receptors
      in calcium regulation and initiation of apoptosis during unfolded protein
      response. 

PMID- 25859936
TI  - Drinking water quality and chronic kidney disease of unknown etiology (CKDu):
      synergic effects of fluoride, cadmium and hardness of water.
AB  - High prevalence of chronic kidney disease of unknown etiology (CKDu) in some
      regions of the world is suspected mainly due to a toxin-mediated renal failure.
      We examined the incidence of CKDu and potable chemical water quality in a CKDu
      affected region. This region has been identified as a high-risk zone for CKDu
      (location: latitude: 8.3500 degrees -9.0000 degrees , longitude: 80.3833 degrees 
      81.3000 degrees , North Central Province, NCP, Sri Lanka) by the World Health
      Organization (WHO). However, within this macro-region, small pockets of CKDu non
      prevalence zones do exist; notably, the residents in those pockets consume spring
      water. Therefore, the drinking water quality of four areas, namely high-CKDu
      prevalence areas (zone I), low-CKDu-prevalence area (zone II), the CKDu-free
      isolated pockets (zone III) and control areas (controls) were examined for F, Al,
      Cd, and As, and hardness and the statistical analysis were carried out to probe
      possible correlations among these parameters. The fluoride and hardness
      concentrations of water in zone III and control areas are much lower compared to
      zones I and II, and the water hardness is ~61 mg/L CaCO3. In zones I and II, the
      harness of drinking water is ~121-180 mg/L CaCO3; however, Al, Cd and As
      concentrations are almost comparable and below WHO recommendations. In most of
      the locations in zones I and II, the F concentration in drinking water is higher
      than the WHO recommendations. The peculiar distribution patterns of CKDu point to
      a synergic effect of trace elements in water for etiology of the disease. 

PMID- 25859937
TI  - Ambient air particulates and particulate-bound mercury Hg(p) concentrations: dry
      deposition study over a Traffic, Airport, Park (T.A.P.) areas during years of
      2011-2012.
AB  - The main purpose of this study was to monitor ambient air particles and
      particulate-bound mercury Hg(p) in total suspended particulate (TSP)
      concentrations and dry deposition at the Hung Kuang (Traffic), Taichung airport
      and Westing Park sampling sites during the daytime and nighttime, from 2011 to
      2012. In addition, the calculated/measured dry deposition flux ratios of ambient
      air particles and particulate-bound mercury Hg(p) were also studied with Baklanov
      & Sorensen and the Williams models. For a particle size of 10 MUm, the Baklanov &
      Sorensen model yielded better predictions of dry deposition of ambient air
      particulates and particulate-bound mercury Hg(p) at the Hung Kuang (Traffic),
      Taichung airport and Westing Park sampling site during the daytime and nighttime
      sampling periods. However, for particulates with sizes 20-23 MUm, the results
      obtained in the study reveal that the Williams model provided better prediction
      results for ambient air particulates and particulate-bound mercury Hg(p) at all
      sampling sites in this study. 

PMID- 25859938
TI  - Thyroglossal duct cyst excision with hyoid bone preservation.
AB  - The objective of this study is to assess complete removal of the thyroglossal
      duct cyst (TGDC) and its tract(s) to the base of the tongue with sparing of the
      hyoid bone. This is a prospective cohort study. Tertiary hospital (Zagazig
      university hospital). This prospective study was carried out on 21 patients who
      had been diagnosed preoperatively as TGDC or fistula. All patients were managed
      by dissection and removal of the TGDC and its tract(s) to the base of the tongue
      with sparing of the hyoid bone. The study was conducted on 12 males (57.14 %) and
      9 females (42.85 %) with mean age 6.8 years (4-20 years). After histopathological
      examination; 16 patients (9 male and 7 female) were proved to have TGDC and 5
      patients (3 male and 2 female) were proved to have dermoid cyst. The hyoid bone
      could be preserved in all cases except in two cases for whom the middle third of
      the hyoid bone was removed with the specimen. Multiple tracts were found in three
      cases and could be identified and dissected successfully with sparing of the
      hyoid bone. Identification, dissection, and complete excision of the TGDC with
      its attaching tract(s) could be performed without hyoid bone resection with no
      recurrence and minimal minor complication. The impacts of this hyoid bone
      preservation versus removal on the pattern of swallowing and retroglossal space
      need to be studied. 

PMID- 25859940
TI  - Structural basis of protein-protein interactions.
AB  - Regulated interactions between proteins govern signaling pathways within and
      between cells. Structural studies on protein complexes formed reversibly and/or
      transiently illustrate the remarkable diversity of interactions, both in terms of
      interfacial size and nature. In recent years, "domain-peptide" interactions have
      gained much greater recognition and may be viewed as both pre-translational and
      posttranslational-dependent functional switches. Our understanding of the
      multistep regulation of auto-inhibited multidomain proteins has also grown. Their
      activity may be understood as the "combinatorial" output of multiple input
      signals, including phosphorylation, location, and mechanical force. The prospects
      for bridging the gap between the new "systems biology" data and the traditional
      "reductionist" data are also discussed. 

PMID- 25859939
TI  - Bioelectrical impedance phase angle and subjective global assessment in detecting
      malnutrition among newly diagnosed head and neck cancer patients.
AB  - Malnutrition, which can be determined by subjective and objective methods, has a
      high prevalence in head and neck cancer patients. Subjective Global Assessment is
      a subjective method of nutritional status evaluation. Phase angle, determined by
      bioelectrical impedance analysis, is proposed as an objective nutritional marker
      in various disease conditions. The study was conducted to investigate the
      association between phase angle and Subjective Global Assessment to validate the
      determination of the nutrition status in adult patients with head and neck
      cancer. In a prospective cohort study, patients were classified as either well
      nourished or malnourished using the Subjective Global Assessment. Phase angle
      measured by bioelectrical impedance analysis was planned in 75 naive patients
      with histologically confirmed head and neck cancer. Receiver operating
      characteristic curves were estimated using the non-parametric method to determine
      the optimal cut-off level of phase angle. The study was conducted on a cohort
      population of 75 patients. Well-nourished patients (n = 45) had a statistically
      significantly higher (p = 0.005) median phase angle score (5.25o) as compared to
      those who were malnourished (4.73o) (n = 30). A phase angle cut-off of 4.73 was
      80 % sensitive and 56.7 % specific in detecting malnutrition diagnosed by SGA in
      these populations. Phase angle is considered to be a nutritional indicator in
      patients with head and neck cancer in detecting malnutrition. Further
      observations are needed to calculate survival, and validate the prognostic
      significance of phase angle. For future studies, it is important to indicate the
      specificity of the PA in comparison to SGA measurement.

PMID- 25859941
TI  - Quantitative analysis of protein-protein interactions.
AB  - Numerous authors, including contributors to this volume, have described methods
      to detect protein-protein interactions. Many of these approaches are now
      accessible to the inexperienced investigator thanks to core facilities and/or
      affordable instrumentation. This chapter discusses some common design
      considerations that are necessary to obtain valid measurements, as well as the
      assumptions and analytical methods that are relevant to the quantitation of these
      interactions. 

PMID- 25859942
TI  - Protein-protein interaction databases.
AB  - Years of meticulous curation of scientific literature and increasingly reliable
      computational predictions have resulted in creation of vast databases of protein
      interaction data. Over the years, these repositories have become a basic
      framework in which experiments are analyzed and new directions of research are
      explored. Here we present an overview of the most widely used protein-protein
      interaction databases and the methods they employ to gather, combine, and predict
      interactions. We also point out the trade-off between comprehensiveness and
      accuracy and the main pitfall scientists have to be aware before adopting protein
      interaction databases in any single-gene or genome-wide analysis. 

PMID- 25859943
TI  - Computational prediction of protein-protein interactions.
AB  - The prediction of protein-protein interactions and kinase-specific
      phosphorylation sites on individual proteins is critical for correctly placing
      proteins within signaling pathways and networks. The importance of this type of
      annotation continues to increase with the continued explosion of genomic and
      proteomic data, particularly with emerging data categorizing posttranslational
      modifications on a large scale. A variety of computational tools are available
      for this purpose. In this chapter, we review the general methodologies for these
      types of computational predictions and present a detailed user-focused tutorial
      of one such method and computational tool, Scansite, which is freely available to
      the entire scientific community over the Internet. 

PMID- 25859944
TI  - Structure-based computational approaches for small-molecule modulation of protein
      protein interactions.
AB  - Three-dimensional structures of proteins offer an opportunity for the rational
      design of small molecules to modulate protein-protein interactions. The presence
      of a well-defined binding pocket on the surface of protein complexes,
      particularly at their interface, can be used for docking-based virtual screening
      of chemical libraries. Several approaches have been developed to identify binding
      pockets that are implemented in programs such as SiteMap, fpocket, and FTSite.
      These programs enable the scoring of these pockets to determine whether they are
      suitable to accommodate high-affinity small molecules. Virtual screening of
      commercial or combinatorial libraries can be carried out to enrich these
      libraries and select compounds for further experimental validation. In virtual
      screening, a compound library is docked to the target protein. The resulting
      structures are scored and ranked for the selection and experimental validation of
      top candidates. Molecular docking has been implemented in a number of computer
      programs such as AutoDock Vina. We select a set of protein-protein interactions
      that have been successfully inhibited with small molecules in the past. Several
      computer programs are applied to identify pockets on the surface, and molecular
      docking is conducted in an attempt to reproduce the binding pose of the
      inhibitors. The results highlight the strengths and limitations of computational
      methods for the design of PPI inhibitors. 

PMID- 25859945
TI  - Targeting protein-protein interactions for drug discovery.
AB  - Protein-protein interactions are associated with key activities and pathways in
      the cell, and in that regard are promising targets for drug discovery. However,
      in terms of small molecule drugs, this promise has not been realized. The
      physical nature of many protein-protein interaction surfaces renders them unable
      to support binding of small drug-like molecules. In addition, there are other
      unique hurdles presented by this class that make the drug development process
      difficult and risky. Nevertheless, success stories have begun to steadily appear
      in this field. These experiences are starting to provide general strategies and
      tools to help overcome the problems inherent in pursuing protein-protein
      interaction targets. These lessons should improve the rate of success as these
      systems are pursued in the future. 

PMID- 25859946
TI  - Studying protein-protein interactions using surface plasmon resonance.
AB  - Protein-protein interactions regulate many important cellular processes,
      including carbohydrate and lipid metabolism, cell cycle and cell death
      regulation, protein and nucleic acid metabolism, signal transduction, and
      cellular architecture. A complete understanding of cellular function depends on
      full characterization of the complex network of cellular protein-protein
      interactions, including measurements of their kinetic and binding properties.
      Surface plasmon resonance (SPR) is one of the commonly used technologies for
      detailed and quantitative studies of protein-protein interactions and
      determination of their equilibrium and kinetic parameters. SPR provides excellent
      instrumentation for a label-free, real-time investigation of protein-protein
      interactions. This chapter details the experimental design and proper use of the
      instrumentation for a kinetic experiment. It will provide readers with basic
      theory, assay setup, and the proper way of reporting this type of results with
      practical tips useful for SPR-based studies. A generic protocol for immobilizing
      ligands using amino coupling chemistry, also useful if an antibody affinity
      capture approach is used, performing kinetic studies, and collecting and
      analyzing data is described. 

PMID- 25859947
TI  - Resonant waveguide grating for monitoring biomolecular interactions.
AB  - Label-free detection technologies have been widely used to characterize
      biomolecular interactions without having to label the target molecules. These
      technologies exhibit considerable potential in facilitating assay development and
      enabling new integrated readouts. When combined with high-throughput capability,
      label-free detection may be applied to small molecule screens for drug
      candidates. Based on the resonant waveguide grating biosensors, a label-free high
      throughput detection system, the Epic((r)) System, has been applied to monitor
      molecular interactions. Here we describe a generic label-free assay to
      quantitatively measure phospho-specific interactions between a trafficking signal
      phosphorylated SWTY peptide and 14-3-3 proteins or anti-phosphopeptide
      antibodies. Compared with the solution-based fluorescence anisotropy assay, our
      results support that the high-throughput resonant waveguide grating biosensor
      system has shown the capability not only for high-throughput characterization of
      binding rank and affinity but also for the exploration of potential interacting
      kinases for the substrates. Hence, it provides a new generic HTS platform for
      phospho-detection. 

PMID- 25859948
TI  - Quartz microbalance technology for probing biomolecular interactions.
AB  - Quartz crystal microbalance with dissipation monitoring (QCM-D) is a useful
      technique for observing the adsorption of molecules onto a protein-functionalized
      surface in real time. This technique is based on relating changes in the
      frequency of a piezoelectric sensor chip, onto which molecules are adsorbing, to
      changes in mass using the Sauerbrey equation. Here, we outline the cleaning,
      preparation, and analysis involved in a typical QCM-D experiment, from which one
      can obtain mass adsorption and kinetic binding information. 

PMID- 25859949
TI  - Label-free kinetic analysis of an antibody-antigen interaction using biolayer
      interferometry.
AB  - Biolayer Interferometry (BLI) is a powerful technique that enables direct
      measurement of biomolecular interactions in real time without the need for
      labeled reagents. Here we describe the analysis of a high-affinity binding
      interaction between a monoclonal antibody and purified antigen using BLI. A
      simple Dip-and-ReadTM format in which biosensors are dipped into microplate wells
      containing purified or complex samples provides a highly parallel, user-friendly
      technique to study molecular interactions. A rapid rise in publications citing
      the use of BLI technology in a wide range of applications, from biopharmaceutical
      discovery to infectious diseases monitoring, suggests broad utility of this
      technology in the life sciences. 

PMID- 25859950
TI  - Characterization of protein-protein interactions by isothermal titration
      calorimetry.
AB  - The analysis of protein-protein interactions has attracted the attention of many
      researchers from both a fundamental point of view and a practical point of view.
      From a fundamental point of view, the development of an understanding of the
      signaling events triggered by the interaction of two or more proteins provides
      key information to elucidate the functioning of many cell processes. From a
      practical point of view, understanding protein-protein interactions at a
      quantitative level provides the foundation for the development of antagonists or
      agonists of those interactions. Isothermal Titration Calorimetry (ITC) is the
      only technique with the capability of measuring not only binding affinity but the
      enthalpic and entropic components that define affinity. Over the years,
      isothermal titration calorimeters have evolved in sensitivity and accuracy.
      Today, TA Instruments and MicroCal market instruments with the performance
      required to evaluate protein-protein interactions. In this methods paper, we
      describe general procedures to analyze heterodimeric (porcine pancreatic trypsin
      binding to soybean trypsin inhibitor) and homodimeric (bovine pancreatic alpha
      chymotrypsin) protein associations by ITC. 

PMID- 25859951
TI  - Sedimentation equilibrium studies.
AB  - The reversible formation of protein-protein interactions plays a crucial role in
      many biological processes. In order to carry out a thorough quantitative
      characterization of these interactions it is essential to establish the
      oligomerization state of the individual components first. The sedimentation
      equilibrium method is ideally suited to perform these studies because it allows a
      reliable, accurate, and absolute value of the solution molecular weight of a
      macromolecule to be obtained. This technique is independent of the shape of the
      macromolecule under investigation and allows the determination of equilibrium
      constants for a monomer-multimer self-associating system. 

PMID- 25859952
TI  - Detecting protein-protein interactions by gel filtration chromatography.
AB  - Upon protein-protein interaction, the formed complex is subject to a change in
      size. A number of methods can be utilized to detect such a change. Gel filtration
      technology is well recognized for its ability to monitor and separate protein
      species of different sizes, and can greatly facilitate functional studies of
      protein complexes. In addition, gel filtration can be performed in any buffer
      system that preserves the protein complex formation and function. Therefore, it
      can be a significantly useful method for studying protein interactions. In this
      chapter, a protocol for performing gel filtration is described in detail. 

PMID- 25859953
TI  - Using light scattering to determine the stoichiometry of protein complexes.
AB  - The stoichiometry of a protein complex can be calculated from an accurate
      measurement of the complex's molecular weight. Multiangle laser light scattering
      in combination with size exclusion chromatography and interferometric
      refractometry provides a powerful means for determining the molecular weights of
      proteins and protein complexes. In contrast to conventional size exclusion
      chromatography and analytical centrifugation, measurements do not rely on the use
      of molecular weight standards and are not affected by the shape of the proteins.
      The technique is based on the direct relationship between the amount of light
      scattered by a protein in solution, and the product of its concentration and
      molecular weight. A typical experimental configuration includes a size exclusion
      column to fractionate the sample, a light scattering detector to measure
      scattered light, and an interferometric refractometer to measure protein
      concentration. The determination of the molecular weight of an anthrax toxin
      complex will be used to illustrate how multiangle laser light scattering can be
      used to determine the stoichiometry of protein complexes. 

PMID- 25859954
TI  - Circular dichroism (CD) analyses of protein-protein interactions.
AB  - Circular dichroism (CD) spectroscopy is a useful technique for studying protein
      protein interactions in solution. CD in the far ultraviolet region (178-260 nm)
      arises from the amides of the protein backbone and is sensitive to the
      conformation of the protein. Thus, CD can determine whether there are changes in
      the conformation of proteins when they interact. Changes in the conformation of
      the protein complexes as a function of temperature or added denaturants, compared
      to the individual proteins, can be used to determine binding constants. CD bands
      in the near ultraviolet (350-260 nm) and visible regions arise from aromatic
      amino acid side chains and prosthetic groups. There are often changes in these
      regions when proteins bind to each other. Because CD is a quantitative technique,
      these changes are directly proportional to the amount of the protein-protein
      complexes formed and thus also can be used to estimate binding constants. 

PMID- 25859955
TI  - Protein-protein interaction analysis by nuclear magnetic resonance spectroscopy.
AB  - Nuclear magnetic resonance (NMR) has continued to evolve as a powerful method,
      with an increase in the number of pulse sequences and techniques available to
      study protein-protein interactions. In this chapter, a straightforward method to
      map a protein-protein interface and design a structural model is described, using
      chemical shift perturbation, paramagnetic relaxation enhancement, and data-driven
      docking. 

PMID- 25859956
TI  - Quantitative protein analysis by mass spectrometry.
AB  - Mass spectrometry is one of the most sensitive methods in analytical chemistry,
      and its application in proteomics has been rapidly expanded after sequencing the
      human genome. Mass spectrometry is now the mainstream approach for identification
      and quantification of proteins and posttranslational modifications, either in
      small scale or in the entire proteome. Shotgun proteomics can analyze up to
      10,000 proteins in a comprehensive study, with detection sensitivity in the
      picogram range. In this chapter, we describe major experimental steps in a
      shotgun proteomics platform, including sample preparation in the context of
      studying protein-protein interaction, mass spectrometric data acquisition, and
      database search to identify proteins and posttranslational modification analysis.
      Proteome quantification strategies and bioinformatics analysis are also
      illustrated. Finally, we discuss the capabilities, limitations, and potential
      improvements of current platforms. 

PMID- 25859957
TI  - Using peptide arrays created by the SPOT method for defining protein-protein
      interactions.
AB  - Evaluating sites of protein-protein interactions can be an arduous task involving
      extensive mutagenesis work and attempts to express and purify individual proteins
      in sufficient quantities. Peptide mapping is a useful alternative to traditional
      methods as it allows rapid detection of regions and/or individual residues
      important for binding, and it can be readily applied to numerous proteins at
      once. Here we describe the use of the ResPep SL SPOT method to evaluate protein
      protein binding interactions such as that between G-protein betagamma subunits
      and SNARE proteins, identifying both regions of interest and subsequently
      individual residues which can then be manipulated in further biochemical assays
      to confirm their validity. 

PMID- 25859958
TI  - Fluorescence polarization assay to quantify protein-protein interactions: an
      update.
AB  - A fluorescence polarization assay can be used to evaluate the strength of a
      protein-protein interaction. A green fluorescent protein variant is fused to one
      of the protein partners. The formation of a complex is then deduced from an
      increase in fluorescence polarization, and the equilibrium dissociation constant
      of the complex is determined in a homogeneous aqueous environment. The assay is
      demonstrated by using the interaction of the S-protein and S-peptide fragments of
      ribonuclease A as a case study. 

PMID- 25859959
TI  - Forster resonance energy transfer (FRET) microscopy for monitoring biomolecular
      interactions.
AB  - Forster or Fluorescence resonance energy transfer (FRET) can be used to detect
      protein-protein interactions. When combined with microscopy, FRET has high
      temporal and spatial resolution, allowing the interaction dynamics of proteins
      within specific subcellular compartments to be detected in cells. FRET microscopy
      has become a powerful technique to assay the direct binding interaction of two
      proteins in vivo. Here, we describe a sensitized emission method to determine the
      presence and dynamics of protein-protein interactions in living cells. 

PMID- 25859960
TI  - Utilizing ELISA to monitor protein-protein interaction.
AB  - Enzyme-linked immunosorbent assay (ELISA) is a commonly used method in analyzing
      biomolecular interactions. As a rapid, specific, and easy-to-operate method,
      ELISA has been used as a research tool as well as a widely adopted diagnostic
      method in clinical settings and for microbial testing in various industries.
      Inhibition ELISA is a one-site binding analysis method, which can monitor protein
      protein interactions in solution as opposed to more commonly used sandwich ELISA
      in which the analyte capture step is required on a solid surface either through
      specific capture or through passive adsorption. Here, we introduce inhibition
      ELISA procedures, using a recombinant viral protein as an example, with emphasis
      on how inhibition ELISA could be used to probe subtle protein conformational
      changes in solution impacting protein-protein binding affinity. Inhibition ELISA
      is used to probe one binding site at a time for binding partners in solution with
      unrestricted conformation. The assay can be performed in a quantitative manner
      with a serially diluted analyte in solution for solution antigenicity or binding
      activity assessment. 

PMID- 25859961
TI  - Glutathione-S-transferase (GST)-fusion based assays for studying protein-protein
      interactions.
AB  - Glutathione-S-transferase (GST)-fusion proteins have become an effective reagent
      to use in the study of protein-protein interactions. GST-fusion proteins can be
      produced in bacterial and mammalian cells in large quantities and purified
      rapidly. GST can be coupled to a glutathione matrix, which permits its use as an
      effective affinity column to study interactions in vitro or to purify protein
      complexes in cells expressing the GST-fusion protein. Here, we provide a
      technical description of the utilization of GST-fusion proteins as both a tool to
      study protein-protein interactions and also as a means to purify interacting
      proteins. 

PMID- 25859962
TI  - Hexahistidine (6xHis) fusion-based assays for protein-protein interactions.
AB  - Fusion-protein tags provide a useful method to study protein-protein
      interactions. One widely used fusion tag is hexahistidine (6xHis). This tag has
      unique advantages over others due to its small size and the relatively low
      abundance of naturally occurring consecutive histidine repeats. 6xHis tags can
      interact with immobilized metal cations to provide for the capture of proteins
      and protein complexes of interest. In this chapter, a description of the benefits
      and uses of 6xHis-fusion proteins as well as a detailed method for performing a
      6xHis-pulldown assay are described. 

PMID- 25859963
TI  - Studying protein-protein interactions via blot overlay/far western blot.
AB  - Blot overlay is a useful method for studying protein-protein interactions. This
      technique involves fractionating proteins on SDS-PAGE, blotting to nitrocellulose
      or PVDF membrane, and then incubating with a probe of interest. The probe is
      typically a protein that is radiolabeled, biotinylated, or simply visualized with
      a specific antibody. When the probe is visualized via antibody detection, this
      technique is often referred to as "Far Western blot." Many different kinds of
      protein-protein interactions can be studied via blot overlay, and the method is
      applicable to screens for unknown protein-protein interactions as well as to the
      detailed characterization of known interactions. 

PMID- 25859964
TI  - Co-immunoprecipitation from transfected cells.
AB  - Co-immunoprecipitation (Co-IP) is one of the most widely used methods to identify
      novel proteins that associate with a protein of interest or to determine complex
      formation between known proteins. For this technique, a protein of interest is
      captured using a specific antibody. The antibody-bound protein, as well as any
      proteins bound to the protein of interest, is then precipitated using a resin
      (immunoprecipitation, IP). Proteins that are not bound to the protein of interest
      are then removed from the sample with a series of washes. The resulting
      immunocomplexes are then analyzed by immunoblot. As the requirements for protein
      protein interactions vary, optimal experimental conditions for examining the
      interacting partners of different proteins of interest must be determined
      empirically. Once appropriate experimental conditions have been established, the
      IP/Co-IP procedure is simple and straightforward. In this chapter, a standard
      protocol for IP/co-IP, with several key factors for the success of IP/co-IP
      analyses, is discussed. 

PMID- 25859965
TI  - In vivo protein cross-linking.
AB  - In the cell, homo- and hetero-associations of polypeptide chains evolve and take
      place within subcellular compartments that are crowded with many other cellular
      macromolecules. In vivo chemical cross-linking of proteins is a powerful method
      to examine changes in protein oligomerization and protein-protein interactions
      upon cellular events such as signal transduction. This chapter is intended to
      provide a guide for the selection of cell membrane permeable cross-linkers, the
      optimization of in vivo cross-linking conditions, and the identification of
      specific cross-links in a cellular context where the frequency of random
      collisions is high. By combining the chemoselectivity of the homo-bifunctional
      cross-linker and the length of its spacer arm with knowledge on the protein
      structure, we show that selective cross-links can be introduced specifically on
      either the dimer or the hexamer form of the same polypeptide in vitro as well as
      in vivo, using the human type B nucleoside diphosphate kinase as a protein model.

PMID- 25859966
TI  - Identification of protein-protein interactions by standard gal4p-based yeast two
      hybrid screening.
AB  - Yeast two-hybrid (Y2H) screening permits identification of completely new protein
      interaction partners for a protein of interest, in addition to confirming binary
      protein-protein interactions. After discussing the general advantages and
      drawbacks of Y2H and existing alternatives, this chapter provides a detailed
      protocol for traditional Gal4p-based Y2H library screens in Saccharomyces
      cerevisiae AH109. This includes bait transformation, bait auto-activation
      testing, prey library transformation, Y2H evaluation, and subsequent
      identification of the prey plasmids. Moreover, a one-on-one mating protocol to
      confirm interactions between suspected partners is given. Finally, a quantitative
      alpha-galactosidase assay protocol to compare interaction strengths is provided. 

PMID- 25859967
TI  - Reverse two-hybrid techniques in the yeast Saccharomyces cerevisiae.
AB  - Use of the yeast two-hybrid system has provided definition to many previously
      uncharacterized pathways through the identification and characterization of novel
      protein-protein interactions. The two-hybrid system uses the bifunctional nature
      of transcription factors, such as the yeast enhancer Gal4, to allow protein
      protein interactions to be monitored through changes in transcription of reporter
      genes. Once a positive interaction has been identified, either of the interacting
      proteins can be mutated by site-specific or randomly introduced changes, to
      produce proteins with a decreased ability to interact. Mutants generated using
      this strategy are very powerful reagents in tests of the biological significance
      of the interaction and in defining the residues involved in the interaction. Such
      techniques are termed reverse two-hybrid methods. We describe a reverse two
      hybrid method that generates loss-of-interaction mutations of the catalytic
      subunit of the Escherichia coli heat-labile toxin (LTA1) with decreased binding
      to the active (GTP-bound) form of human ARF3, its protein cofactor. While newer
      methods are emerging for performing interaction screens in mammalian cells,
      instead of yeast, the use of reverse two-hybrid in yeast remains a robust and
      powerful means of identifying loss-of-interaction point mutants and compensating
      changes that remain among the most powerful tools of testing the biological
      significance of a protein-protein interaction. 

PMID- 25859968
TI  - MAPPIT, a mammalian two-hybrid method for in-cell detection of protein-protein
      interactions.
AB  - MAPPIT (MAmmalian Protein-Protein Interaction Trap) is a two-hybrid technology
      that facilitates the detection and analysis of interactions between proteins in
      living mammalian cells. The system is based on type 1 cytokine receptor
      signaling. The bait protein of interest is fused to a chimeric signaling
      deficient cytokine receptor, the signaling competence of which is restored upon
      recruitment of a prey protein that is coupled to a functional cytokine receptor
      domain. MAPPIT exhibits an excellent signal-to-noise ratio, detects a wide
      variety of protein-protein interactions (PPIs) including transient and indirect
      interactions, and has been shown to be highly complementary to other two-hybrid
      methods with respect to the interactions it can detect. Variants of the method
      were developed to allow large-scale PPI screening, mapping of protein interaction
      interfaces, PPI inhibitor screening and drug profiling. This chapter describes a
      basic 4-day MAPPIT protocol for the analysis of interaction between two
      designated proteins. 

PMID- 25859969
TI  - Bioluminescence resonance energy transfer to detect protein-protein interactions
      in live cells.
AB  - Bioluminescence resonance energy transfer (BRET) is a valuable tool to detect
      protein-protein interactions. BRET utilizes bioluminescent and fluorescent
      protein tags with compatible emission and excitation properties, making it
      possible to examine resonance energy transfer when the tags are in close
      proximity (<10 nm) as a typical result of protein-protein interactions. Here we
      describe a protocol for detecting BRET from two known protein binding partners
      (Galphai1 and RGS14) in HEK 293 cells using Renilla luciferase and yellow
      fluorescent protein tags. We discuss the calculation of the acceptor/donor ratio
      as well as net BRET and demonstrate that BRET can be used as a platform to
      investigate the regulation of protein-protein interactions in live cells in real
      time. 

PMID- 25859970
TI  - Mapping biochemical networks with protein fragment complementation assays.
AB  - Cellular biochemical machineries, what we call pathways, consist of dynamically
      assembling and disassembling macromolecular complexes. Although our models for
      the organization of biochemical machines are derived largely from in vitro
      experiments, do they reflect their organization in intact, living cells? We have
      developed a general experimental strategy that addresses this question by
      allowing the quantitative probing of molecular interactions in intact, living
      cells. The experimental strategy is based on Protein fragment Complementation
      Assays (PCA), a method whereby protein interactions are coupled to refolding of
      enzymes from cognate fragments where reconstitution of enzyme activity acts as
      the detector of a protein interaction. A biochemical machine or pathway is
      defined by grouping interacting proteins into those that are perturbed in the
      same way by common factors (hormones, metabolites, enzyme inhibitors, etc.). In
      this chapter we review some of the essential principles of PCA and provide
      details and protocols for applications of PCA, particularly in mammalian cells,
      based on three PCA reporters, dihydrofolate reductase, green fluorescent protein,
      and beta-lactamase. 

PMID- 25859971
TI  - Detection of protein-protein interaction using bimolecular fluorescence
      complementation assay.
AB  - The bimolecular fluorescence complementation (BiFC) assay is a versatile
      technique for investigating protein-protein interaction (PPI) in living systems.
      The BiFC assay exploits the color-emitting moiety and the modular structure of
      fluorescent proteins to provide both temporal and spatial information of the PPI.
      The modular property of fluorescent proteins enables researchers to strategically
      partition a fluorescent protein into two nonfluorescent units, which can be
      independently fused to other proteins. When the fusion proteins interact with
      each other, the nonfluorescent fragments reconstitute to generate a fluorescence
      signal. PPI can then be detected by capturing the fluorescence signal with a
      fluorescence microscope. In this chapter, the Venus fluorescent protein is
      employed to demonstrate the application of the BiFC assay. 

PMID- 25859972
TI  - Split-luciferase complementation assay to detect channel-protein interactions in
      live cells.
AB  - The understanding of ion channel function continues to be a significant driver in
      molecular pharmacology. In this field of study, protein-protein interactions are
      emerging as fundamental molecular determinants of ion channel function and as
      such are becoming an attractive source of highly specific targets for drug
      development. The investigation of ion channel macromolecular complexes, however,
      still relies on conventional methods that are usually technically challenging and
      time-consuming, significantly hampering our ability to identify, characterize and
      modify ion channel function through targeted molecular approaches. As a response
      to the urgent need of developing rapid and albeit accurate technologies to survey
      ion channel molecular complexes, we describe a new application of the split
      luciferase complementation assay to study the interaction of the voltage-gated Na
      + channel with the intracellular fibroblast growth factor 14 and its dynamic
      regulation in live cells. We envision that the flexibility and accessibility of
      this assay will have a broad impact in the ion channel field complementing
      structural and functional studies, enabling the interrogation of protein-channel
      dynamic interactions in complex cellular contexts and laying the basis for new
      frameworks in drug discovery campaigns. 

PMID- 25859973
TI  - Confocal microscopy for intracellular co-localization of proteins.
AB  - Confocal laser scanning microscopy is the best method to visualize intracellular
      co-localization of proteins in intact cells. Because of the point scan/pinhole
      detection system, light contribution from the neighborhood of the scanning spot
      in the specimen can be eliminated, allowing high Z-axis resolution. Fluorescence
      detection by sensitive photomultiplier tubes allows the usage of filters with a
      narrow bandpath, resulting in minimal cross-talk (overlap) between two spectra.
      This is particularly important in demonstrating co-localization of proteins with
      multicolor labeling. Here, the methods outlining the detection of transiently
      expressed tagged proteins and the detection of endogenous proteins are described.
      Ideally, the intracellular co-localization of two endogenous proteins should be
      demonstrated. However, when antibodies raised against the protein of interest are
      unavailable for immunofluorescence or the available cell lines do not express the
      protein of interest sufficiently enough for immunofluorescence, an alternative
      method is to transfect cells with expression plasmids that encode tagged proteins
      and stain the cells with anti-tag antibodies. However, it should be noted that
      the tagging of proteins of interest or their overexpression could potentially
      alter the intracellular localization or the function of the target protein. 

PMID- 25859974
TI  - Fluorescence polarization assay to quantify protein-protein interactions in an
      HTS format.
AB  - Fluorescence polarization (FP) technology is based on the measurement of molecule
      rotation, and has been widely used to study molecular interactions in solution.
      This method can be used to measure binding and dissociation between two molecules
      if one of the binding molecules is relatively small and fluorescent. The
      fluorescently labeled small molecule (such as a small peptide) rotates rapidly in
      the solution. Upon excitation by polarized light, the emitted light remains
      depolarized and gives rise to a low FP signal. When the fluorescent small
      molecules in solution are bound to bigger molecules (such as a protein), the
      movement of the complex becomes slower. When such a complex is excited with
      polarized light, much of the emitted light is polarized because of the slow
      movement of the complex. Thus, the binding of a fluorescently labeled small
      molecule to a bigger molecule can be monitored by the change in polarization and
      measured by the generation of an increased FP signal. This chapter aims to
      provide a step-by-step practical procedure for developing an FP assay in a multi
      well plate format to monitor protein-protein interaction (PPI) in a homogenous
      format. 

PMID- 25859975
TI  - Estrogen receptor alpha/co-activator interaction assay: TR-FRET.
AB  - Time-resolved fluorescence resonance energy transfer, TR-FRET, is a time-gated
      fluorescence intensity measurement which defines the relative proximity of two
      biomolecules (e.g., proteins, peptides, or DNA) based on the extent of non
      radiative energy transfer between two fluorophores with overlapping
      emission/excitation spectra. In these assays, an excited lanthanide ion acts as a
      "donor" that transfers energy to an "acceptor" fluorophore through dipole-dipole
      interactions. A FRET signal is reported as the ratio of acceptor to donor
      emission following donor excitation. When a donor-conjugated protein interacts
      with an acceptor-conjugated protein, the donor and acceptor fluorophores are
      brought in close proximity allowing energy transfer from the donor to the
      acceptor resulting in a FRET signal. Because the lanthanide donors have a long
      emission half-life, the energy transfer measurement can be time-gated, which
      dramatically reduces assay interference (due to background autofluorescence and
      direct acceptor excitation) and thereby increases data quality. Here, we describe
      a TR-FRET assay that monitors the interaction of the estrogen receptor (ER) alpha
      ligand binding domain (labeled with a terbium chelate via a streptavidin-biotin
      interaction) with a sequence of coactivator protein SRC3 (labeled directly with
      fluorescein) and the disruption of this interaction with a peptide and a small
      molecule inhibitor. 

PMID- 25859976
TI  - High content screening biosensor assay to identify disruptors of p53-hDM2 protein
      protein interactions.
AB  - This chapter describes the implementation of the p53-hDM2 protein-protein
      interaction (PPI) biosensor (PPIB) HCS assay to identify disruptors of p53-hDM2
      PPIs. Recombinant adenovirus expression constructs were generated bearing the
      individual p53-GFP and hDM2-RFP PPI partners. The N-terminal p53 transactivating
      domain that contains the binding site for hDM2 is expressed as a GFP fusion
      protein that is targeted and anchored in the nucleolus of infected cells by a
      nuclear localization (NLS) sequence. The p53-GFP biosensor is localized to the
      nucleolus to enhance and facilitate the image acquisition and analysis of the
      PPIs. The N-terminus of hDM2 encodes the domain for binding to the
      transactivating domain of p53, and is expressed as a RFP fusion protein that
      includes both an NLS and a nuclear export sequence (NES). In U-2 OS cells co
      infected with both adenovirus constructs, the binding interactions between hDM2
      and p53 result in both biosensors becoming co-localized within the nucleolus.
      Upon disruption of the p53-hDM2 PPIs, the p53-GFP biosensor remains in the
      nucleolus while the shuttling hDM2-RFP biosensor redistributes into the
      cytoplasm. p53-hDM2 PPIs are measured by acquiring fluorescent images of cells co
      infected with both adenovirus biosensors on an automated HCS imaging platform and
      using an image analysis algorithm to quantify the relative distribution of the
      hDM2-RFP shuttling component of the biosensor between the cytoplasm and nuclear
      regions of compound treated cells. 

PMID- 25859977
TI  - Case Study: discovery of inhibitors of the MDM2-p53 protein-protein interaction.
AB  - The p53 protein, a tumor suppressor, is inactivated in many human cancers through
      mutations or by its interaction with an oncoprotein, MDM2. Blocking the MDM2-p53
      protein-protein interaction has the effect of activating wild-type p53 and has
      been pursued as a novel anticancer strategy. Small-molecule inhibitors of the
      MDM2-p53 interaction have been discovered through various approaches, and a
      number of them have progressed into clinical trials for cancer treatment. Here,
      we describe the methods and techniques used in the discovery of small-molecule
      inhibitors of the MDM2-p53 interaction. 

PMID- 25859978
TI  - Biophysical methods for identifying fragment-based inhibitors of protein-protein
      interactions.
AB  - Fragment-based lead discovery complements high-throughput screening and computer
      aided drug design for the discovery of small-molecule inhibitors of protein
      protein interactions. Fragments are molecules with molecular masses ca 280 Da or
      smaller, and are generally screened using structural or biophysical approaches.
      Several methods of fragment-based screening are feasible for any soluble protein
      that can be expressed and purified; specific techniques also have size
      limitations and/or require multiple milligrams of protein. This chapter describes
      some of the most common fragment-discovery methods, including surface plasmon
      resonance, nuclear magnetic resonance, differential scanning fluorimetry, and X
      ray crystallography. 

PMID- 25859980
TI  - Plenary symposia.

PMID- 25859979
TI  - HIF-1alpha disturbs osteoblasts and osteoclasts coupling in bone remodeling by up
      regulating OPG expression.
AB  - Hypoxia-inducible factor 1alpha (HIF-1alpha) is one of the master regulators of
      hypoxia reactions, playing an important role in bone modeling, remodeling, and
      homeostasis. And overexpression of HIF-1alpha in mature osteoblasts through
      conditional deletion of the von Hippel-Lindau (VHL) gene profoundly increases
      angiogenesis and osteogenesis. Studies showed that mice with osteoblasts lacking
      Vhl had a high level of Hif-1alpha and increased bone mass and density. On the
      contrary, Hif-1alpha conditional knockout mice had decreased bone mass and
      density. Our in vitro study showed that osteoprotegerin (OPG), an essential
      regulator of osteoclastic activity, can be upregulated by HIF-1alpha and in turn
      downregulate the resorption activity of osteoclasts. We showed that HIF-1alpha
      may directly bind to the upstream site of OPG and enhance its expression. Our
      study suggested that a novel mechanism, which works via OPG signaling, may
      mediate the function of HIF-1alpha in bone remodeling. 

PMID- 25859982
TI  - Hesperidin, a Citrus Flavonoid, Has the Ameliorative Effects Against Experimental
      Autoimmune Encephalomyelitis (EAE) in a C57BL/J6 Mouse Model.
AB  - The aim of this study was determined the effects of Hesperidin (HP) on neuronal
      damage in brain tissue caused by Experimental allergic encephalomyelitis (EAE),
      an established model of multiple sclerosis in C57BL/J6 mice. To explore 40 mice
      were equally divided into four groups: (1) Control, (2) EAE, (3) HP, and (4) HP +
      EAE. 14 days after induction of EAE with MOG35-55 and pertussis toxin, the mice
      treated with HP at the doses of 50 mg/kg/day for 7 days subcutaneously. To our
      results HP treatment prevents the oxidative stress caused by EAE via a decrease
      in lipid peroxidations and increase in elements of the antioxidant defense
      systems in brain tissue. Also, EAE elevate the IL-17, express the pro
      inflammatory cytokines, and caspase-3-like immunreactivity, show apoptosis,
      staining in EAE mice brain and increased the incidence of histopathological
      damage. However, immonohistochemical and histological changes were reversed with
      HP. Moreover, elevated TNF-alpha and IL-1beta levels, a result of EAE, were
      decreased in serum and neurological deficits as clinical signs were reversed with
      HP treatment in EAE mice, given HP. In conclusion, HP treatment effectively
      prevents oxidative, immunological and histological damage in the brain caused by
      EAE. It was thought that the beneficial effects of HP are likely a result of its
      strong antioxidant and anti-inflammatory properties.

PMID- 25859983
TI  - Teduglutide: a guide to its use in short bowel syndrome.
AB  - Teduglutide (Gattex((r))) is a recombinant analogue of human glucagon-like
      peptide-2 and is indicated for the treatment of adults with short bowel syndrome
      (SBS) dependent on parenteral support (PS). In a pivotal, 24-week clinical trial
      in SBS patients, subcutaneous teduglutide 0.05 mg/kg once daily increased
      absorption from the remnant intestine as evidenced by significant reductions in
      PS volume requirements versus placebo. Improvements attained in absorption in the
      first 6 months of therapy were maintained during the extension trial (total
      teduglutide treatment periods of up to 30 months), with evidence indicating that
      benefits accrue over time. Among patients who received teduglutide treatment for
      up to 30 months, 11 of 30 were able to achieve at least one additional day off PS
      and another ten achieved complete independence from PS. Subcutaneous teduglutide
      was generally well tolerated in clinical trials, including over the long term,
      with most adverse events that led to study discontinuation being gastrointestinal
      in origin.

PMID- 25859984
TI  - CyberKnife radiosurgery leading to long-lasting complete remission in locally
      relapsed solitary plasmacytoma of the bone.

PMID- 25859981
TI  - Integrated multimodal imaging of dynamic bone-tumor alterations associated with
      metastatic prostate cancer.
AB  - Bone metastasis occurs for men with advanced prostate cancer which promotes
      osseous growth and destruction driven by alterations in osteoblast and osteoclast
      homeostasis. Patients can experience pain, spontaneous fractures and morbidity
      eroding overall quality of life. The complex and dynamic cellular interactions
      within the bone microenvironment limit current treatment options thus prostate to
      bone metastases remains incurable. This study uses voxel-based analysis of
      diffusion-weighted MRI and CT scans to simultaneously evaluate temporal changes
      in normal bone homeostasis along with prostate bone metatastsis to deliver an
      improved understanding of the spatiotemporal local microenvironment. Dynamic
      tumor-stromal interactions were assessed during treatment in mouse models along
      with a pilot prospective clinical trial with metastatic hormone sensitive and
      castration resistant prostate cancer patients with bone metastases. Longitudinal
      changes in tumor and bone imaging metrics during delivery of therapy were
      quantified. Studies revealed that voxel-based parametric response maps (PRM) of
      DW-MRI and CT scans could be used to quantify and spatially visualize dynamic
      changes during prostate tumor growth and in response to treatment thereby
      distinguishing patients with stable disease from those with progressive disease
      (p<0.05). These studies suggest that PRM imaging biomarkers are useful for
      detection of the impact of prostate tumor-stromal responses to therapies thus
      demonstrating the potential of multi-modal PRM image-based biomarkers as a novel
      means for assessing dynamic alterations associated with metastatic prostate
      cancer. These results establish an integrated and clinically translatable
      approach which can be readily implemented for improving the clinical management
      of patients with metastatic bone disease.

PMID- 25859985
TI  - Agreement of point-of-care INR test with standard venous sampling assay at higher
      extreme ranges.

PMID- 25859986
TI  - Monitoring anticoagulant therapy with vitamin K antagonists in patients with
      antiphospholipid syndrome.
AB  - Because of the possible interference of antiphospholipid antibodies (APL) with
      the phospholipid component of thromboplastin reagents, concerns have been raised
      about the validity of international normalized ratio (INR) testing to monitor
      anticoagulant therapy with vitamin K antagonists in patients with
      antiphospholipid syndrome (APS). To investigate the reliability of the INR, we
      determined the INR using various prothrombin time (PT) assays and compared the
      results with those of a chromogenic factor X (CFX) assay. The study cohort
      consisted of 40 APS patients and 100 APL-negative patients who were on
      anticoagulant therapy for reasons other than APS. The agreement (i.e. the
      percentage of patients with a difference <=0.5 INR units) between the PT-derived
      INR and CFX-derived INR equivalents was only moderate in both patient groups. The
      best agreement with CFX-derived INR equivalents was observed for the Thromborel S
      reagent in APS patients (69.1 %) and for Neoplastin Plus in APL-negative patients
      (72.0 %). Regarding the results for the point-of-care system CoaguChek XS, an
      agreement between the INR and the CFX-derived INR equivalent was less frequently
      observed in the APS patients (55.6 vs. 67.8 %; p = 0.050). When considering all
      3058 pairs of INR tests within the international sensitivity index (ISI)
      calibrated range of 1.5 to 4.5 s, we did not observe a higher variability of INR
      values in either the APS patient group or the subgroup of APS patients positive
      for lupus coagulants compared with the APL-negative controls. In conclusion,
      monitoring vitamin K antagonists (VKA) therapy with laboratory INR measurements
      seems to be suitable for the majority of APS patients. 

PMID- 25859987
TI  - MDR-TB recurrence after successful treatment: additional studies using molecular
      genotyping are needed.

PMID- 25859988
TI  - Occupational asthma in developing countries requires further research.

PMID- 25859989
TI  - Hippocrates and tuberculosis.

PMID- 25859990
TI  - The epidemiological advantage of preferential targeting of tuberculosis control
      at the poor.
AB  - Tuberculosis (TB) remains disproportionately concentrated among the poor, yet
      known determinants of TB reactivation may fail to explain observed disparities in
      disease rates according to wealth. Reviewing data on TB disparities in India and
      the wealth distribution of known TB risk factors, we describe how social mixing
      patterns could be contributing to TB disparities. Wealth-assortative mixing,
      whereby individuals are more likely to be in contact with others from similar
      socio-economic backgrounds, amplifies smaller differences in risk of TB,
      resulting in large population-level disparities. As disparities and
      assortativeness increase, TB becomes more difficult to control, an effect that is
      obscured by looking at population averages of epidemiological parameters, such as
      case detection rates. We illustrate how TB control efforts may benefit from
      preferential targeting toward the poor. In India, an equivalent-scale
      intervention could have a substantially greater impact if targeted at those
      living below the poverty line than with a population-wide strategy. In addition
      to potential efficiencies in targeting higher-risk populations, TB control
      efforts would lead to a greater reduction in secondary TB cases per primary case
      diagnosed if they were preferentially targeted at the poor. We highlight the need
      to collect programmatic data on TB disparities and explicitly incorporate equity
      considerations into TB control plans. 

PMID- 25859991
TI  - F-A-S-T: a refocused, intensified, administrative tuberculosis transmission
      control strategy.

PMID- 25859992
TI  - QTc prolongation and treatment of multidrug-resistant tuberculosis.
AB  - Electrocardiographic (ECG) monitoring is recommended for some of the new and re
      purposed drugs used in the treatment of multidrug-resistant tuberculosis (MDR
      TB), as these drugs have been shown to prolong the QTc interval. ECG monitoring
      is relatively new in the management of TB patients, and has several implications
      for programs and providers. This review discusses what is known about QTc
      prolongation and the medications currently being studied or used to treat MDR-TB,
      and discusses strategies for managing QTc prolongation in the context of treating
      such a serious infectious disease. It also reviews some major implications of ECG
      monitoring in the field, including interpretation of ECGs and QTc intervals,
      management of patients with prolonged QTc intervals, and contextualizing the risk
      of QTc prolongation for patients being treated for MDR-TB. 

PMID- 25859993
TI  - The impact of Xpert((r)) MTB/RIF in sparsely populated rural settings.
AB  - BACKGROUND: The impact of implementing Xpert((r)) MTB/RIF and the choice of
      instrument placement on patient care in sparsely populated areas with poor access
      to laboratory and radiology services have not yet been elucidated. METHODS:
      Prospective evaluation of three diagnostic approaches in the Central Karoo, South
      Africa: smear microscopy as the initial diagnostic, with sputum processing at
      centralised laboratories, and Xpert as the initial diagnostic with instrument
      placement at facility level or centralised laboratory. RESULTS: Of 1449
      individuals, 196 were diagnosed with TB. The proportion positive on initial
      testing was respectively 8%, 20% and 8% during the smear microscopy,
      decentralised Xpert and centralised Xpert periods. The proportion of
      bacteriologically confirmed cases was respectively 88%, 99% and 91% during the
      smear microscopy, decentralised Xpert and centralised Xpert periods. The median
      time to treatment was respectively 11.5 (interquartile range [IQR] 6-24), 1 (IQR
      0-2) and 6 days (IQR 2-9) during the smear microscopy, decentralised Xpert and
      centralised Xpert periods. CONCLUSION: Introducing Xpert as the initial
      diagnostic in areas with poor access to TB diagnostics increased the proportion
      of cases with bacteriological confirmation and reduced time to treatment
      initiation; however, point-of-care placement may have resulted in fewer people
      being evaluated for TB.

PMID- 25859994
TI  - Low rates of recurrence after successful treatment of multidrug-resistant
      tuberculosis in Tomsk, Russia.
AB  - SETTING: Tomsk, Russia, where multidrug-resistant tuberculosis (MDR-TB) is
      prevalent. OBJECTIVES: To report rates of recurrence following successful
      treatment of MDR-TB in a program providing individualized treatment regimens
      designed according to the current global standard of care. DESIGN: A
      retrospective cohort study of 408 adults successfully treated for pulmonary MDR
      TB from 10 September 2000 to 1 November 2004, and followed for up to 6 years post
      treatment. We used Poisson regression with generalized estimating equations to
      assess whether recurrence rates changed significantly with time. RESULTS: We
      analyzed 399 (97.5%) patients with at least one follow-up visit (15 850 person
      months of observation [PMO]). Baseline resistance to second-line drugs was common
      (65.2%); 398 patients (99.7%) were human immunodeficiency virus (HIV) negative.
      In the first year of post-treatment follow-up, there were six episodes of
      recurrence (1.4/1000 PMO, 95%CI 0.5-3.0). After the first post-treatment year,
      there were 21 episodes of recurrence (1.8/1000 PMO, 95%CI 1.1-2.8). The rate did
      not change significantly with time. CONCLUSION: Individualized regimens designed
      according to the current global standard of care achieved low rates of MDR-TB
      recurrence among non-HIV-infected persons treated in a programmatic setting.

PMID- 25859995
TI  - Highly successful treatment outcome of multidrug-resistant tuberculosis in the
      Netherlands, 2000-2009.
AB  - SETTING: Resistance to the two key anti-tuberculosis drugs isoniazid and
      rifampicin is a characteristic of multidrug-resistant tuberculosis (MDR-TB). MDR
      TB is a scourge requiring toxic, prolonged treatment and is associated with poor
      outcomes. The Netherlands is a country with a long-standing, integrated, well
      resourced TB service where all patients are offered culture-confirmed diagnosis
      by a central reference laboratory. OBJECTIVE: To assess the treatment outcomes of
      MDR-TB patients over a period of 10 years in The Netherlands. DESIGN:
      Demographic, clinical and microbiological features of all patients with MDR-TB
      who started treatment in 2000-2009 in the Netherlands were analysed from national
      registry and patient records. RESULTS: Characteristics of the 113 MDR-TB patients
      were as follows: male/female ratio 1.57, 96% foreign born, median age 29 years,
      96 (85%) pulmonary TB, 56 (50%) smear-positive, 14 (12%) human immunodeficiency
      virus (HIV) co-infected. Of the 104 (92%) patients who started MDR-TB treatment,
      86% had a successful outcome using a median of six active drugs; eight underwent
      pulmonary surgery. HIV negativity was associated with successful outcome
      (adjusted OR 2.1, 95%CI 1.1-3.8). CONCLUSION: High success rates for MDR-TB
      treatment were achieved with close collaboration of all stakeholders, reaching
      the targets set for drug-susceptible TB. HIV remained an independent risk factor
      for unsuccessful treatment outcome.

PMID- 25859996
TI  - Treatment interruption and directly observed treatment of multidrug-resistant
      tuberculosis patients in China.
AB  - BACKGROUND: China has nearly one fifth of global multidrug-resistant tuberculosis
      (MDR-TB) cases, and follows the 24-month World Health Organization (WHO)
      standardised regimens. OBJECTIVE: To assess treatment interruption among MDR-TB
      patients and its association with the provision of directly observed treatment
      (DOT). METHODS: We reviewed clinical charts and conducted a questionnaire survey
      among all confirmed MDR-TB patients who had been treated for at least 6 months
      from 1 January 2009 to 30 April 2012 in Shandong Province. Treatment interruption
      was defined as missing a dose for at least 1 day but for <8 consecutive weeks;
      the subset 'severe interruption' was defined as missing doses for 2-8 consecutive
      weeks. RESULTS: Of 110 patients, 75 (68%) interrupted treatment; 19 (17%)
      reported severe interruption, with a median duration of 30 days. Of the 110
      patients, 26 (24%) received injections from family members and 55 (50%) received
      DOT, 7 (13%) from village doctors and 48 (87%) from family members. Patients who
      underwent DOT with a family member had less severe interruptions (OR 0.25, 95%CI
      0.05-0.98) than those who were given DOT by a village doctor or who did not
      undergo DOT. CONCLUSIONS: Family members may act as treatment supporters for MDR
      TB patients to reduce treatment interruptions, but require orientation on their
      role.

PMID- 25859997
TI  - Phenotypic and genotypic diversity in a multinational sample of drug-resistant
      Mycobacterium tuberculosis isolates.
AB  - OBJECTIVE: To develop and evaluate rapid, molecular-based drug susceptibility
      testing (DST) for extensively drug-resistant tuberculosis (XDR-TB), we assembled
      a phenotypically and genotypically diverse collection of Mycobacterium
      tuberculosis isolates from patients evaluated for drug resistance in four high
      burden countries. METHODS: M. tuberculosis isolates from India (n = 111), Moldova
      (n = 90), the Philippines (n = 96), and South Africa (n = 103) were selected from
      existing regional and national repositories to maximize phenotypic diversity for
      resistance to isoniazid, rifampin (RMP), moxifloxacin, ofloxacin, amikacin,
      kanamycin, and capreomycin. MGITTM 960 was performed on viable isolates in one
      laboratory using standardized procedures and drug concentrations. Genetic
      diversity within drug resistance phenotypes was assessed. RESULTS: Nineteen
      distinct phenotypes were observed among 400 isolates with complete DST results.
      Diversity was greatest in the Philippines (14 phenotypes), and least in South
      Africa (9 phenotypes). Nearly all phenotypes included multiple genotypes. All
      sites provided isolates resistant to injectables but susceptible to
      fluoroquinolones. Many patients were taking drugs to which their disease was
      resistant. DISCUSSION: Diverse phenotypes for XDR-TB-defining drugs, including
      resistance to fluoroquinolones and/or injectable drugs in RMP-susceptible
      isolates, indicate that RMP susceptibility does not ensure effectiveness of a
      standard four-drug regimen. Rapid, low-cost DST assays for first- and second-line
      drugs are thus needed.

PMID- 25859998
TI  - Mycobacterium tuberculosis genotypic drug resistance patterns and clustering in
      Jayapura, Papua, Indonesia.
AB  - BACKGROUND: Little is known about drug-resistant tuberculosis (TB) and its
      transmission in Papua, which has one of the highest rates of TB in Indonesia.
      DESIGN: We examined genotypic drug resistance patterns using multiplex ligation
      dependent probe amplification and the degree of molecular clustering using 24
      locus mycobacterial interspersed repetitive units-variable number of tandem
      repeats (MIRU-VNTR) among 199 consecutive pulmonary TB patients in Jayapura,
      Papua. RESULTS: Drug resistance mutations were present in 30/198 (15.2%)
      patients: 16/144 (11.1%) primary cases and 14/51 (27.5%) retreatment cases.
      Genotypic resistance to rifampicin was found in 15 (7.6%) patients, to isoniazid
      in 19 (9.6%), to ethambutol in 7 (3.5%), and to streptomycin and second-line
      injectable drugs in 5 (2.5%) patients. Eight (4.0%) patients had multidrug
      resistant TB, while no mutations were found for fluoroquinolones. The most common
      lineage found among all isolates was East-African Indian (n = 66, 33.7%),
      followed by Euro-American (n = 38, 19.4%). Drug resistance mutations were more
      common among Beijing strains than other lineages. Of the 30 drug-resistant
      isolates, 12 (40.0%) fell into four clusters that were separate from drug
      susceptible clusters as determined using MIRU-VNTR. CONCLUSIONS: These are the
      first genotypic drug resistance data from Jayapura, Papua, showing moderate rates
      of resistance to first-line drugs and likely transmission of drug-resistant TB.

PMID- 25859999
TI  - Genetic mutations associated with rifampicin and isoniazid resistance in MDR-TB
      patients in North-West India.
AB  - BACKGROUND: Effective tuberculosis (TB) control has been hindered by the
      emergence of multidrug-resistant TB (MDR-TB). OBJECTIVE: To analyse the frequency
      of drug resistance among presumed cases of drug-resistant TB in the state of
      Punjab, India, and to determine the frequency of various genetic mutations
      detected using the line-probe assay (LPA). METHODS: Eight hundred patients with
      presumptive drug-resistant TB were enrolled under the programmatic management of
      drug-resistant TB under India's Revised National Tuberculosis Control Programme.
      Sputum samples from these patients were subjected to smear microscopy and LPA.
      Clinicodemographic details along with drug resistance patterns and genetic
      mutations were studied. RESULTS: After excluding non-eligible samples, 545
      samples were analysed, of which 290 (53.2%) showed resistance. Isoniazid and
      rifampicin (RMP) monoresistance were detected in respectively 9.3% (51/545) and
      18% (98/545) of samples, while MDR was present in 25.8% (141/545) of samples. Of
      the MDR-TB cases, 2.1% (3/141) were treatment-naive, while 90.8% (128/141) were
      on retreatment. The most common mutation conferring RMP resistance was S531L.
      CONCLUSION: All patients undergoing retreatment for TB should be tested for drug
      susceptibility at the initial evaluation. Factors responsible for high MDR-TB and
      heteroresistance in Punjab need further studies.

PMID- 25860000
TI  - Rifampicin pharmacokinetics in children under the Revised National Tuberculosis
      Control Programme, India, 2009.
AB  - OBJECTIVE: To evaluate serum levels of rifampicin (RMP) in children with
      tuberculosis (TB) at doses administered according to India's Revised National
      Tuberculosis Control Programme (RNTCP) 2009 report. METHOD: Prospective, open
      label, non-randomised single-dose study in 20 children aged 5-12 years. SETTING:
      The out-patient chest clinic of a tertiary care hospital, New Delhi, India.
      RESULTS: The median RMP dose administered was 9.56 mg/kg (range 9-12.64). Peak
      RMP concentration (Cmax) attained was 6.24 MUg/ml (range 5.44-7.61) at time to
      Cmax of 3.5 h (range 3-4). RMP levels were significantly lower at 2, 3 and 4 h in
      children administered <10 mg/kg than those who received ?10 mg/kg (P < 0.05). A
      positive correlation between the RMP dose administered and Cmax was observed
      (r(2) = 0.748). RMP Cmax was <8 MUg/ml in all patients, a level considered too
      low for therapeutic efficacy. CONCLUSIONS: Low serum concentrations of RMP were
      attained in children under the RNTCP 2009 weight band system. Peak RMP levels
      appear to be lower and the single dose elimination half-life shorter in children
      than in adults. To optimise treatment outcomes, revisions in RMP dose in children
      should take into consideration age-related differences in pharmacokinetics.

PMID- 25860001
TI  - Novel application of NIH case definitions in a paediatric tuberculosis contact
      investigation study.
AB  - BACKGROUND: International (National Institutes of Health [NIH]) case definitions
      have been proposed for paediatric tuberculosis (TB) diagnostic studies. The
      relevance of these definitions for contact tracing studies is unknown. METHODS:
      We developed case definitions for a community-based contact tracing diagnostic
      study. We compare disease certainty using protocol-defined and NIH case
      definitions and describe TB disease spectrum and severity. RESULTS: There were
      111 potential disease episodes in 109 (21% human immunodeficiency virus [HIV]
      infected) of 1093 children enrolled. Based on NIH definitions, there were 8
      confirmed, 12 probable, 17 possible and 3 unlikely TB and 2 non-TB episodes.
      Using protocol case definitions, there were 23 episodes of confirmed, 36
      probable, 27 possible and 0 unlikely TB and 21 non-TB. Of 111 potential episodes,
      69 were unclassifiable using the NIH definition, while 4 were unclassifiable
      using the protocol definition. Agreement between definitions was 0.30 (95%CI 0.23
      0.38). There were 62 episodes (72%) of non-severe and 24 (28%) of severe TB.
      CONCLUSIONS: The NIH definition had limited applicability to household contact
      studies, despite the wide spectrum of disease observed. Further research is
      needed to develop case definitions relevant to different research settings,
      including contact investigation to capture the wide spectrum of paediatric TB in
      clinical research.

PMID- 25860002
TI  - Immunogenicity of BCG in HIV-exposed and non-exposed infants following routine
      birth or delayed vaccination.
AB  - BACKGROUND: Human immunodeficiency virus (HIV) exposed infants are at high risk
      of Mycobacterium tuberculosis exposure, have high rates of progression to
      tuberculosis (TB) disease and are at significant risk of bacille Calmette-Guerin
      (BCG) induced adverse events. OBJECTIVE: To evaluate a delayed BCG vaccination
      strategy in HIV-exposed infants. DESIGN: A randomised trial of routine BCG
      vaccination given at birth compared to 14 weeks of age in HIV-exposed non
      infected and non-HIV-exposed infants to investigate longitudinal BCG-induced
      immune responses using a 7-day whole blood interferon-gamma (IFN-gamma) enzyme
      linked immunosorbent assay. RESULTS: A significantly higher proportion of infants
      had positive responses to M. tuberculosis purified protein derivative (PPD) and
      BCG at 14 weeks in the birth vs. delayed vaccination groups (P = 0.001 for both).
      This difference was no longer apparent at weeks 24 or 52. Among infants
      vaccinated at birth, the 14-week IFN-gamma response to M. tuberculosis PPD was
      lower among HIV-exposed than non-exposed infants (276.5 pg/ml vs. 790.2, P =
      0.048). Among all infants, there were significant correlations between the
      magnitude of IFN-gamma responses to BCG, M. tuberculosis PPD, TB 10.4 and culture
      filtrate protein 10/early secreted antigenic target 6. CONCLUSIONS: The timing of
      vaccination had limited effect on BCG-induced IFN-gamma responses, which waned
      considerably over 1 year despite initial vigorous responses in both vaccination
      groups. The lower responses in HIV-exposed non-infected infants suggest
      potentially altered mycobacterial immunity early in life.

PMID- 25860003
TI  - Tuberculosis among nomads in Adamawa, Nigeria: outcomes from two years of active
      case finding.
AB  - BACKGROUND: Nomadic populations are often isolated and have difficulty accessing
      health care, leading to increased morbidity and mortality. Although Nigeria has
      one of the highest tuberculosis (TB) burdens in Africa, case detection rates
      remain relatively low. METHODS: Active case finding for TB among nomadic
      populations was implemented over a 2-year period in Adamawa State. A total of 378
      community screening days were organised with local leaders; community volunteers
      provided treatment support. Xpert((r)) MTB/RIF was available for nomads with
      negative smear results. RESULTS: Through active case finding, 96 376 nomads were
      verbally screened, yielding 1310 bacteriologically positive patients. The number
      of patients submitting sputum for smear microscopy statewide increased by 112%
      compared with the 2 years before the intervention. New smear-positive
      notifications increased by 49.5%, while notifications of all forms of TB
      increased by 24.5% compared with expected notifications based on historical
      trends. Nomads accounted for respectively 31.4% and 26.0% of all smear-positive
      and all forms TB notifications. Pre-treatment loss to follow-up and treatment
      outcomes were similar among nomads and non-nomads. DISCUSSION: Nomads in Nigeria
      have high TB rates, and active case-finding approaches may be useful in
      identifying and successfully treating them. Large-scale interventions in
      vulnerable populations can improve TB case detection.

PMID- 25860004
TI  - Applying spatiotemporal models to study risk of smear-positive tuberculosis in
      Iran, 2001-2012.
AB  - SETTING: Assessing tuberculosis (TB) distribution in regions over time is
      essential for health officials to have a proper understanding of current status,
      determine high-risk areas, and improve case management and resource allocation.
      OBJECTIVE: To evaluate spatial distribution and trends in the risk of smear
      positive Mycobacterium tuberculosis in Iran during 2001-2012 using spatiotemporal
      models. DESIGN: Overall and province-specific trends in TB risk were estimated
      using a Bayesian spatiotemporal model. We obtained Bayesian posterior
      probabilities to test the hypothesis of the relative risk (RR) being equal to 1
      and the significance of TB trends in each province. RESULTS: Estimated
      countrywide trends declined at a rate of almost 3% per decade. The RR was the
      highest in the provinces of Sistan and Baluchestan, followed by Golestan,
      Khorasan-Razavi, Hormozgan, Qom, Guilan and South Khorasan. Upward temporal
      trends were observed in nine provinces. CONCLUSION: TB risk was generally high in
      provinces bordering high TB burden countries; population movements from high-risk
      provinces and adjacent countries appear to be the main challenge to TB control.
      Nevertheless, the declining risk pattern in these provinces indicates good, but
      inadequate, progress with TB control. Different health policies according to TB
      risk and trend are required for each province.

PMID- 25860005
TI  - Role of bicyclol in preventing drug-induced liver injury in tuberculosis patients
      with liver disease.
AB  - SETTING: Four hospitals in China. OBJECTIVE: To evaluate the clinical efficacy
      and safety of using bicyclol in conjunction with glucurolactone in preventing
      drug-induced liver injury (DILI) in tuberculosis (TB) patients suffering from
      underlying liver disease. DESIGN: A total of 240 initially treated TB patients
      who were healthy hepatitis B carriers or had pure steatosis were randomised into
      two equal groups; both received an oral glucurolactone tablet 600 mg/day (200 mg
      three times daily) as basic liver protection. The test group also received 75
      mg/day (25 mg three times daily) bicyclol tablets orally, while the control group
      received no other liver protection. The incidence of liver injury in the two
      groups, the adjustment or termination of anti-tuberculosis chemotherapy and any
      adverse reactions were assessed. RESULTS: The incidence rate and level of
      severity of liver injury and the termination rate of anti-tuberculosis treatment
      in the test group were lower than that of the control group (P < 0.05). The
      overall time of occurrence of liver injury was significantly different between
      the two groups (P < 0.05). CONCLUSION: Adding bicyclol to basic liver protectants
      may effectively and safely prevent the occurrence of anti-tuberculosis DILI in
      patients with underlying liver disease, and help simplify anti-tuberculosis
      treatment.

PMID- 25860006
TI  - Waterpipe a gateway to cigarette smoking initiation among adolescents in Irbid,
      Jordan: a longitudinal study.
AB  - SETTING: According to anecdotal evidence, waterpipe smoking may lead to the
      initiation of cigarette smoking among young people. This hypothesis is yet to be
      examined using an appropriate study design and a theoretical model for behavioral
      change. OBJECTIVE: To compare the risk of cigarette smoking initiation among
      waterpipe-only smokers and never smokers in a school-based sample of adolescents
      from Irbid, Jordan. METHODS: A total of 1454 cigarette-naive participants were
      drawn from a longitudinal study on smoking behavior conducted in Irbid among 1781
      seventh graders who were enrolled at baseline (2008) and completed the study
      questionnaire on smoking behavior annually until 2011. Grouped time-survival
      analysis was used to compare the risk of subsequent initiation of cigarette
      smoking between waterpipe smokers (n = 298) and never smokers (n = 1156) using
      adjusted hazard ratios (aHRs) and 95% confidence intervals (95%CI). RESULTS: Risk
      of initiation of cigarette smoking among waterpipe smokers was significantly
      higher than among never smokers after adjusting for potential confounders (aHR
      1.67, 95%CI 1.46-1.92). The association between waterpipe and cigarette smoking
      initiation was dose-dependent. The risk of initiating cigarette smoking increased
      with increase in the frequency of waterpipe smoking (P for linear trend < 0.001).
      CONCLUSIONS: Waterpipe smoking led to the initiation of cigarette smoking among
      this cohort of Jordanian adolescents; the effect was dose-dependent.

PMID- 25860007
TI  - Change in peak expiratory flow over time among workers exposed to polyvinyl
      chloride dust.
AB  - OBJECTIVE: To evaluate the variation of peak expiratory flow (PEF) over a working
      week among non-smoking workers without previous asthma who have been exposed to
      polyvinyl chloride (PVC) dust. DESIGN: We conducted a cross-sectional study among
      42 operators with exposure to PVC dust (filling hoppers to feed extrusion
      machines) and 23 employees without exposure to PVC dust in a plant producing PVC
      pipes in West Africa. A pre-tested questionnaire was administered and PEF was
      measured using a portable peak flow meter after a day off (day 1), on day 3 and
      at the end of the week (day 6). RESULTS: The two groups did not differ by age or
      body mass index. Dyspnoea was more prevalent in exposed workers than controls
      (52% vs. 13%, P = 0.002). PEF decreased more significantly in exposed workers
      than controls (-8% vs. -3% on day 3 and -10% vs. -5% on day 6, both P = 0.004).
      The duration of exposure did not affect PEF variability in the exposed groups.
      CONCLUSION: The decrease of PEF over the working week in workers exposed to PVC
      dust is consistent with occupational asthma, although standard measures to
      diagnose occupational asthma were not used. This result reinforces the need to
      prevent excessive exposure to PVC dust.

PMID- 25860008
TI  - Multidrug-resistant tuberculosis in Ukraine at a time of military conflict.

PMID- 25860009
TI  - Implementation of the Stop TB strategy in a large TB hospital in Ukraine:
      achievements and deficiencies.

PMID- 25860010
TI  - Safe and effective treatment for patients with isoniazid drug resistance.

PMID- 25860011
TI  - False-positive Xpert((r)) MTB/RIF assays and previous treatment.

PMID- 25860012
TI  - In reply.

PMID- 25860013
TI  - A longitudinal study of the health status of a community of religious sisters:
      addressing the advantages, challenges, and limitations.
AB  - Longitudinal studies are recognized as contributing to understanding the
      complexity of aging and generating insights that cannot be gained using other
      research methods. However, conducting longitudinal studies is recognized as
      challenging, especially among older adults. The purpose of the current review is
      to describe how the authors addressed the limitations and challenges of
      longitudinal studies in a study of the health status of a community of religious
      sisters. Methods of this specific longitudinal study are presented to provide
      background to the discussion. Challenges, limitations, and advantages of the
      current longitudinal study are organized into three categories (i.e., sample,
      method, and data analysis) that have been addressed in the literature as
      contributing to the fidelity of longitudinal studies. The unique characteristics
      of the current study sample, particularly their access to health care, creates a
      comparison group for the study of older women in general.

PMID- 25860014
TI  - Correction: Descriptive anatomy and three-dimensional reconstruction of the skull
      of the early tetrapod Acanthostega gunnari Jarvik, 1952.

PMID- 25860015
TI  - The development of the skull of the Egyptian Cobra Naja h. haje (Squamata:
      Serpentes: Elapidae).
AB  - BACKGROUND: The study of craniofacial development is important in understanding
      the ontogenetic processes behind morphological diversity. A complete
      morphological description of the embryonic skull development of the Egyptian
      cobra, Naja h. haje, is lacking and there has been little comparative discussion
      of skull development either among elapid snakes or between them and other snakes.
      METHODOLOGY/PRINCIPAL FINDINGS: We present a description of skull development
      through a full sequence of developmental stages of the Egyptian cobra, and
      compare it to other snakes. Associated soft tissues of the head are noted where
      relevant. The first visible ossification centres are in the supratemporal,
      prearticular and surangular, with slight ossification visible in parts of the
      maxilla, prefrontal, and dentary. Epiotic centres of ossification are present in
      the supraoccipital, and the body of the supraoccipital forms from the tectum
      posterior not the tectum synoticum. The venom glands are visible as distinct
      bodies as early at stage 5 and enlarge later to extend from the otic capsule to
      the maxilla level with the anterior margin of the eye. The gland becomes more
      prominent shortly before hatching, concomitant with the development of the fangs.
      The tongue shows incipient forking at stage 5, and becomes fully bifid at stage
      6. CONCLUSIONS/SIGNIFICANCE: We present the first detailed staging series of
      cranial development for the Egyptian cobra, Naja h. haje. This is one of the
      first studies since the classical works of G. de Beer and W. Parker that provides
      a detailed description of cranial development in an advanced snake species. It
      allows us to correct errors and misinterpretations in previous accounts which
      were based on a small sample of specimens of uncertain age. Our results highlight
      potentially significant variation in supraoccipital formation among squamates and
      the need for further research in this area.

PMID- 25860018
TI  - Correction: Higuchi dimension of digital images.

PMID- 25860016
TI  - Malaria care in infants aged under six months in Uganda: an area of unmet needs!
AB  - BACKGROUND: Little information exists on malaria burden, artemisinin-based
      combination therapy (ACT) use, and malaria care provided to infants under six
      months of age. The perception that malaria may be rare in this age group has led
      to lack of clinical trials and evidence-based treatment guidelines. The objective
      of this study was to identify malaria parasitemia positivity rate (MPPR) among
      patients under six months, and practices and predictors of malaria diagnosis and
      treatment in this population. METHODS: Cross-sectional data collected from
      October 2010 to September 2011 on 25,997 individual outpatients aged <6 months
      from 36 health facilities across Uganda were analysed. FINDINGS: Malaria was
      suspected in 18,415 (70.8%) patients, of whom 7,785 (42.3%) were tested for
      malaria. Of those tested, the MPPR was 36.1%, with 63.9% testing negative, of
      which 1,545 (31.1%) were prescribed an antimalarial. Among children <5kgs, off
      label prescription of ACT was high (104/285, 36.5%). Younger age (1-6 days,
      aOR=0.47, p=0.01; 7-31 days, aOR=0.43, p<0.001; and 1-2 months, aOR=0.61,
      p<0.001), pneumonia (aOR=0.78, p=0.01) or cough/cold (aOR=0.65, p<0.001)
      diagnosis, and fever (aOR=0.56, p=0.01) reduced the odds of receiving a malaria
      test. Fever (aOR=2.22, p<0.001), anemia diagnosis (aOR=3.51, p=0.01), consulting
      midwives (aOR=3.58, p=0.04) and other less skilled providers (aOR=4.75, p<0.001)
      relative to medical officers, consulting at hospitals (aOR=3.31, p=0.03),
      visiting health facilities in a medium-high malaria transmission area (aOR=2.20,
      p<0.001), and visiting during antimalarial (aOR=1.82, p=0.04) or antibiotic
      (aOR=2.23, p=0.04) shortages increased the odds of prescribing an antimalarial
      despite a negative malaria test result. CONCLUSIONS: We found high malaria
      suspicion but low testing rates in outpatient children aged <6 months. Among
      those tested, MPPR was high. Despite a negative malaria test result, many infants
      were prescribed antimalarials. Off-label ACT prescription was common in children
      weighing <5kgs. Evidence-based malaria guidelines for infants weighing <5
      kilograms and aged <6 months are urgently needed.

PMID- 25860017
TI  - Surnames and Y-chromosomal markers reveal low relationships in Southern Spain.
AB  - A sample of 416 males from western and eastern Andalusia has been jointly
      analyzed for surnames and Y-chromosome haplogroups and haplotypes. The observed
      number of different surnames was 222 (353 when the second surname of the Spanish
      system of naming is considered). The great majority of recorded surnames have a
      Castilian-Leonese origin, while Catalan or Basque surnames have not been found. A
      few Arab-related surnames appear but none discernible of Sephardic-Jewish
      descent. Low correlation among surnames with different population frequencies and
      Y-chromosome markers, at different levels of genetic resolution, has been
      observed in Andalusia. This finding could be explained mainly by the very low
      rate of monophyletic surnames because of the historical process of surname
      ascription and the resulting high frequencies of the most common Spanish
      surnames. The introduction of surnames in Spain during the Middle Ages coincided
      with Reconquest of the territories under Islamic rule, and Muslims and Jews
      progressively adopted the present male line surname system. Sampled surnames and
      Y-chromosome lineages fit well a power-law distribution and observed isonymy is
      very close to that of the general population. Besides, our data and results show
      that the reliability of the isonymy method should be questioned because of the
      high rate of polyphyletic surnames, even in small geographic regions and
      autochthonous populations. Random isonymy would be consistently dependent of the
      most common surname frequencies in the population. 

PMID- 25860019
TI  - Comparison of peak cardiopulmonary performance parameters on a robotics-assisted
      tilt table, a cycle and a treadmill.
AB  - Robotics-assisted tilt table (RATT) technology provides body support, cyclical
      stepping movement and physiological loading. This technology can potentially be
      used to facilitate the estimation of peak cardiopulmonary performance parameters
      in patients who have neurological or other problems that may preclude testing on
      a treadmill or cycle ergometer. The aim of the study was to compare the magnitude
      of peak cardiopulmonary performance parameters including peak oxygen uptake
      (VO2peak) and peak heart rate (HRpeak) obtained from a robotics-assisted tilt
      table (RATT), a cycle ergometer and a treadmill. The strength of correlations
      between the three devices, test-retest reliability and repeatability were also
      assessed. Eighteen healthy subjects performed six maximal exercise tests, with
      two tests on each of the three exercise modalities. Data from the second tests
      were used for the comparative and correlation analyses. For nine subjects, test
      retest reliability and repeatability of VO2peak and HRpeak were assessed.
      Absolute VO2peak from the RATT, the cycle ergometer and the treadmill was (mean
      (SD)) 2.2 (0.56), 2.8 (0.80) and 3.2 (0.87) L/min, respectively (p < 0.001).
      HRpeak from the RATT, the cycle ergometer and the treadmill was 168 (9.5), 179
      (7.9) and 184 (6.9) beats/min, respectively (p < 0.001). VO2peak and HRpeak from
      the RATT vs the cycle ergometer and the RATT vs the treadmill showed strong
      correlations. Test-retest reliability and repeatability were high for VO2peak and
      HRpeak for all devices. The results demonstrate that the RATT is a valid and
      reliable device for exercise testing. There is potential for the RATT to be used
      in severely impaired subjects who cannot use the standard modalities. 

PMID- 25860020
TI  - tRNAGlu increases the affinity of glutamyl-tRNA synthetase for its inhibitor
      glutamyl-sulfamoyl-adenosine, an analogue of the aminoacylation reaction
      intermediate glutamyl-AMP: mechanistic and evolutionary implications.
AB  - For tRNA-dependent protein biosynthesis, amino acids are first activated by
      aminoacyl-tRNA synthetases (aaRSs) yielding the reaction intermediates aminoacyl
      AMP (aa-AMP). Stable analogues of aa-AMP, such as aminoacyl-sulfamoyl-adenosines,
      inhibit their cognate aaRSs. Glutamyl-sulfamoyl-adenosine (Glu-AMS) is the best
      known inhibitor of Escherichia coli glutamyl-tRNA synthetase (GluRS).
      Thermodynamic parameters of the interactions between Glu-AMS and E. coli GluRS
      were measured in the presence and in the absence of tRNA by isothermal titration
      microcalorimetry. A significant entropic contribution for the interactions
      between Glu-AMS and GluRS in the absence of tRNA or in the presence of the
      cognate tRNAGlu or of the non-cognate tRNAPhe is indicated by the negative values
      of -TDeltaSb, and by the negative value of DeltaCp. On the other hand, the large
      negative enthalpy is the dominant contribution to DeltaGb in the absence of tRNA.
      The affinity of GluRS for Glu-AMS is not altered in the presence of the non
      cognate tRNAPhe, but the dissociation constant Kd is decreased 50-fold in the
      presence of tRNAGlu; this result is consistent with molecular dynamics results
      indicating the presence of an H-bond between Glu-AMS and the 3'-OH oxygen of the
      3'-terminal ribose of tRNAGlu in the Glu-AMS*GluRS*tRNAGlu complex. Glu-AMS being
      a very close structural analogue of Glu-AMP, its weak binding to free GluRS
      suggests that the unstable Glu-AMP reaction intermediate binds weakly to GluRS;
      these results could explain why all the known GluRSs evolved to activate
      glutamate only in the presence of tRNAGlu, the coupling of glutamate activation
      to its transfer to tRNA preventing unproductive cleavage of ATP. 

PMID- 25860022
TI  - Correction: discovery of CTCF-sensitive cis-spliced fusion RNAs between adjacent
      genes in human prostate cells.

PMID- 25860021
TI  - Use of the common marmoset to study Burkholderia mallei infection.
AB  - Burkholderia mallei is a host-adapted bacterium that does not persist outside of
      its equine reservoir. The organism causes the zoonosis glanders, which is endemic
      in Asia, Africa, the Middle East and South America. Infection by B. mallei
      typically occurs via the respiratory or percutaneous route, and the most common
      manifestations are life-threatening pneumonia and bacteremia. Glanders is
      difficult to diagnose and requires prolonged antibiotic therapy with low success
      rates. There is no vaccine to protect against B. mallei and there is concern
      regarding its use as a biothreat agent. Thus, experiments were performed to
      establish a non-human primate model of intranasal infection to study the organism
      and develop countermeasures. Groups of marmosets (Callithrix jacchus) were
      inoculated intranasally with B. mallei strain ATCC 23344 and monitored for
      clinical signs of illness for up to 13 days. We discovered that 83% of marmosets
      inoculated with doses of 2.5 X 10(4) to 2.5 X 10(5) bacteria developed acute
      lethal infection within 3-4 days. Signs of disease were severe and included
      lethargy, inappetence, conjunctivitis, mucopurulent and hemorrhagic nasal
      discharges, and increased respiratory effort with abdominal lifts. Burkholderia
      mallei was cultured from the lungs, spleen and liver of these animals, and
      pathologic examination of tissues revealed lesions characteristic of glanders.
      Challenge experiments also revealed that 91% of animals infected with doses
      ranging from 25 to 2.5 X 10(3) bacteria exhibited mild non-specific signs of
      illness and were culture negative. One marmoset inoculated with 2.5 X 10(3)
      organisms developed moderate signs of disease and reached humane end-points 8
      days post-infection. The liver and spleen of this animal were colonized with the
      agent and pathological analysis of tissues showed nasal, splenic and hepatic
      lesions. Taken together, these data indicate that the marmoset is a suitable
      model to study respiratory infection by B. mallei.

PMID- 25860023
TI  - Characterizing task-based OpenMP programs.
AB  - Programmers struggle to understand performance of task-based OpenMP programs
      since profiling tools only report thread-based performance. Performance tuning
      also requires task-based performance in order to balance per-task memory
      hierarchy utilization against exposed task parallelism. We provide a cost
      effective method to extract detailed task-based performance information from
      OpenMP programs. We demonstrate the utility of our method by quickly diagnosing
      performance problems and characterizing exposed task parallelism and per-task
      instruction profiles of benchmarks in the widely-used Barcelona OpenMP Tasks
      Suite. Programmers can tune performance faster and understand performance
      tradeoffs more effectively than existing tools by using our method to
      characterize task-based performance. 

PMID- 25860024
TI  - Lipid profiles and obesity as potential risk factors of sudden sensorineural
      hearing loss.
AB  - OBJECTIVES: The objective of our study was to establish whether increased lipid
      profiles and obesity affect the prevalence and prognosis of sudden sensorineural
      hearing loss (SSNHL). METHODS: This was a case-controlled study with a
      longitudinal design. According to our criteria, 324 patients with SSNHL were
      included in this study. To manage potential covariates, 972 subjects with normal
      hearing from the Korean National Health and Nutrition Examination Survey were
      matched as control group according to their propensity scores. Age, level of
      total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low-density
      lipoprotein cholesterol (LDL-C), triglycerides (TG), and body mass index (BMI)
      were obtained from the clinical data. Multivariate logistic regression analysis
      was used to investigate the association between SSNHL and lipid profiles or
      obesity in the 1296 subjects. Multivariate Cox regression analysis was used to
      determine whether lipid profiles and obesity are prognostic factors in patients
      with SSNHL. RESULTS: Mean body weight, BMI, TC, and TG were significantly higher
      in patients with SSNHL compared with control subjects (p<0.05). However, LDL-C
      values did not differ significantly between the two groups. Subjects with
      elevated TC and TG levels had a 2.20- (95% CI 1.50-3.24) and 1.50-fold (95% CI
      1.08-2.08) increased odds, respectively, of SSNHL compared with subjects with
      normal TC and TG levels. Subjects with grade III BMI had a 1.59-fold (95% CI 1.17
      2.16) increased odds of SSNHL. Multivariate Cox regression analyses revealed that
      BMI was an independent risk factor of treatment outcome, as patients with BMI
      >=27.5 were less likely to achieve complete recovery than those with BMI <27.5
      (p<0.05). CONCLUSIONS: The results of this study revealed that elevated TC and TG
      levels and increased BMI are significantly associated with the prevalence of
      SSNHL and its prognosis, indicating that vascular compromise may play an
      important role in the pathogenesis of SSNHL.

PMID- 25860026
TI  - Colonic delivery of celecoxib is a potential pharmaceutical strategy for
      repositioning the selective COX-2 inhibitor as an anti-colitic agent.
AB  - Celecoxib is a selective cyclooxygenase-2 inhibitor applied to the treatment of
      arthritis. Repositioning the anti-inflammatory drug as an anti-inflammatory bowel
      disease drug has obstacles such as controversial anti-colitic efficacy and
      potential side effects. We examined whether colonic delivery of celecoxib could
      circumvent the therapeutic limitations. N-succinylglutam-1-yl celecoxib (SG1C), a
      colon-specific prodrug of celecoxib), was administered orally to rats with
      colitis and the anti-inflammatory activity and pharmacologic mechanisms were
      investigated. SG1C alleviated the colonic injury and lowered myeloperoxidase
      activity in the inflamed colonic tissues much more effectively than conventional
      celecoxib. While suppressing expression of pro-inflammatory nuclear factor kappaB
      gene products including cyclooxygenase-2, SG1C elevated an anti-inflammatory
      nuclear factor-erythroid 2 p45 (NF-E2)-related factor 2 (Nrf2) and its target
      gene product heme oxygenase (HO)-1 in the inflamed colon. In contrast, no
      significant molecular effects were observed with conventional celecoxib. Unlike
      conventional celecoxib, SG1C did not lower the serum level of 6-keto-PGF1alpha,
      an inverse indicator of cardiovascular adverse effects. Collectively, colonic
      delivery of celecoxib, likely improving therapeutic and toxicological properties
      of celecoxib, may be a feasible pharmaceutical strategy to therapeutically switch
      celecoxib to an anti-colitic drug. 

PMID- 25860025
TI  - Chronic ouabain treatment induces Rho kinase activation.
AB  - Ouabain is an endogenous Na(+)/K(+)-ATPase inhibitor whose chronic administration
      induces hypertension. Endogenous ouabain levels increase in human essential
      hypertension. On the other hand, Rho/Rho kinase (ROCK) pathway has been
      implicated in various animal models of hypertension. In the current work, we
      evaluated the possible involvement of Rho kinase in ouabain-induced hypertension.
      Ouabain was administered daily (20 ug/kg, i.p.) to Wistar rats for 6 weeks. After
      the ouabain treatment, we evaluated the possible changes in vascular responses to
      KCl and phenylephrine alone and in the presence of Rho kinase inhibitor Y27632.
      We also determined the expressions of ROCKs, Rho A and phosphorylation of myosin
      binding subunit of myosin light chain phosphatase (pMYPT) and activation of Rho
      A. Agonist-induced contractions in the presence of Y27632 are significantly
      decreased and Y27632-induced relaxations in aortas precontracted with
      phenylephrine are significantly enhanced with the chronic treatment of ouabain.
      Although the expressions of ROCK I and ROCK II remained unchanged, pMYPT
      expression was significantly increased in ouabain-treated group. Moreover, Rho A
      expression and activation were decreased after treatment with ouabain. Although
      Rho kinase expression did not change in aortas, increased basal Rho kinase
      activation may contribute to the development of ouabain-induced hypertension. Our
      current data present the first evidence that Rho kinase is involved in the
      development of ouabain-induced hypertension in rats.

PMID- 25860027
TI  - GSK3beta-Dzip1-Rab8 cascade regulates ciliogenesis after mitosis.
AB  - The primary cilium, which disassembles before mitotic entry and reassembles after
      mitosis, organizes many signal transduction pathways that are crucial for cell
      life and individual development. However, how ciliogenesis is regulated during
      the cell cycle remains largely unknown. Here we show that GSK3beta, Dzip1, and
      Rab8 co-regulate ciliogenesis by promoting the assembly of the ciliary membrane
      after mitosis. Immunofluorescence and super-resolution microscopy showed that
      Dzip1 was localized to the periciliary diffusion barrier and enriched at the
      mother centriole. Knockdown of Dzip1 by short hairpin RNAs led to failed ciliary
      localization of Rab8, and Rab8 accumulation at the basal body. Dzip1
      preferentially bound to Rab8GDP and promoted its dissociation from its inhibitor
      GDI2 at the pericentriolar region, as demonstrated by sucrose gradient
      centrifugation of purified basal bodies, immunoprecipitation, and acceptor
      bleaching fluorescence resonance energy transfer assays. By means of in vitro
      phosphorylation, in vivo gel shift, phospho-peptide identification by mass
      spectrometry, and GST pulldown assays, we demonstrated that Dzip1 was
      phosphorylated by GSK3beta at S520 in G0 phase, which increased its binding to
      GDI2 to promote the release of Rab8GDP at the cilium base. Moreover, ciliogenesis
      was inhibited by overexpression of the GSK3beta-nonphosphorylatable Dzip1 mutant
      or by disabling of GSK3beta by specific inhibitors or knockout of GSK3beta in
      cells. Collectively, our data reveal a unique cascade consisting of GSK3beta,
      Dzip1, and Rab8 that regulates ciliogenesis after mitosis. 

PMID- 25860028
TI  - Effects of Dulaglutide on Thyroid C Cells and Serum Calcitonin in Male Monkeys.
AB  - Glucagon-like peptide-1 (GLP-1) receptor agonists, used for the treatment of type
      2 diabetes, have caused hyperplasia/neoplasia of thyroid C cells in rodent
      carcinogenicity studies. Studies in monkeys have not identified an effect of GLP
      1 receptor agonists on thyroid C cells; however, group sizes were small.
      Dulaglutide is a once-weekly, long-acting human GLP-1 receptor agonist recently
      approved in the United States and the European Union. The objective of this study
      was to determine whether dulaglutide altered C-cell mass in monkeys. Male
      cynomolgus monkeys (20 per group) were sc injected with dulaglutide 8.15 mg/kg
      (~500-fold maximum human plasma exposure) or a vehicle control twice weekly for
      52 weeks. Basal and calcium gluconate-stimulated serum calcitonin concentrations
      were obtained at 3, 6, 9, and 12 months. Thyroid glands were weighed, fixed, and
      sectioned at 500-MUm intervals. C-cell volumes were measured using an automated
      image analysis. C-cell proliferation was estimated using Ki67/calcitonin
      colabeling and cell counting. Administration of dulaglutide 8.15 mg/kg twice
      weekly for 52 weeks did not increase serum calcitonin in monkeys or affect
      thyroid weight, histology, C-cell proliferation, or absolute/relative C-cell
      volume. This study represents a comprehensive evaluation of the monkey thyroid C
      cells after dosing with a GLP-1 receptor agonist, with a large group size, and
      measurement of multiple relevant parameters. The lack of effect of dulaglutide on
      C cells is consistent with other studies in monkeys using GLP-1 receptor agonists
      and suggests that nonhuman primates are less sensitive than rodents to the
      induction of proliferative changes in thyroid C cells by GLP-1 receptor agonists.

PMID- 25860029
TI  - Chronic Toxicity and Carcinogenicity Studies of the Long-Acting GLP-1 Receptor
      Agonist Dulaglutide in Rodents.
AB  - The tumorigenic potential of dulaglutide was evaluated in rats and transgenic
      mice. Rats were injected sc twice weekly for 93 weeks with dulaglutide 0, 0.05,
      0.5, 1.5, or 5 mg/kg corresponding to 0, 0.5, 7, 20, and 58 times, respectively,
      the maximum recommended human dose based on plasma area under the curve.
      Transgenic mice were dosed sc twice weekly with dulaglutide 0, 0.3, 1, or 3 mg/kg
      for 26 weeks. Dulaglutide effects were limited to the thyroid C-cells. In rats,
      diffuse C-cell hyperplasia and adenomas were statistically increased at 0.5 mg/kg
      or greater (P <= .01 at 5 mg/kg), and C-cell carcinomas were numerically
      increased at 5 mg/kg. Focal C-cell hyperplasia was higher compared with controls
      in females given 0.5, 1.5, and 5 mg/kg. In transgenic mice, no dulaglutide
      related C-cell hyperplasia or neoplasia was observed at any dose; however,
      minimal cytoplasmic hypertrophy of C cells was observed in all dulaglutide
      groups. Systemic exposures decreased over time in mice, possibly due to an
      antidrug antibody response. In a 52-week study designed to quantitate C-cell mass
      and plasma calcitonin responses, rats received twice-weekly sc injections of
      dulaglutide 0 or 5 mg/kg. Dulaglutide increased focal C-cell hyperplasia;
      however, quantitative increases in C-cell mass did not occur. Consistent with the
      lack of morphometric changes in C-cell mass, dulaglutide did not affect the
      incidence of diffuse C-cell hyperplasia or basal or calcium-stimulated plasma
      calcitonin, suggesting that diffuse increases in C-cell mass did not occur during
      the initial 52 weeks of the rat carcinogenicity study. 

PMID- 25860030
TI  - Increased Bone Turnover and Possible Accelerated Fracture Healing in a Murine
      Model With an Increased Circulating C-Type Natriuretic Peptide.
AB  - Recent studies have revealed that C-type natriuretic peptide (CNP) is a potent
      stimulator of endochondral bone growth. Nevertheless, the effect of CNP on bone
      turnover has not yet been well studied. To elucidate this issue, we investigated
      the bone phenotype of a mouse model with elevated plasma CNP concentrations (SAP
      CNP-Tg mice) in the present study. Microcomputed tomography (CT) analysis
      revealed less bone in femurs, but not in lumber vertebrae, of young adult SAP-CNP
      Tg mice than that of wild-type mice. Bone histomorphometry of the tibiae from 8
      week-old SAP-CNP-Tg mice showed enhanced osteoblastic and osteoclastic
      activities, in accordance with elevated serum levels of osteocalcin and tartrate
      resistant acid phosphatase-5b, respectively. Next we performed an open and
      stabilized femoral fracture using 8-week-old SAP-CNP-Tg mice and compared the
      healing process with age-matched wild-type mice. An immunohistochemical study
      revealed that CNP and its receptors, natriuretic peptide receptor-B and
      natriuretic peptide clearance receptor, are expressed in hard calluses of wild
      type mice, suggesting a possible role of CNP/natriuretic peptide receptor-B
      signaling in fracture repair, especially in bone remodeling stage. On micro-CT
      analysis, a rapid decrease in callus volume was observed in SAP-CNP-Tg mice,
      followed by a generation of significantly higher new bone volume with a tendency
      of increased bone strength. In addition, a micro-CT analysis also showed that
      bone remodeling was accelerated in SAP-CNP-Tg mice, which was also evident from
      increased serum osteocalcin and tartrate-resistant acid phosphatase-5b levels in
      SAP-CNP-Tg mice at the remodeling stage of fracture repair. These results
      indicate that CNP activates bone turnover and remodeling in vivo and possibly
      accelerates fracture healing in our mouse model. 

PMID- 25860031
TI  - MEF2 Cooperates With Forskolin/cAMP and GATA4 to Regulate Star Gene Expression in
      Mouse MA-10 Leydig Cells.
AB  - In Leydig cells, steroidogenic acute regulatory protein (STAR) participates in
      cholesterol shuttling from the outer to the inner mitochondrial membrane, the
      rate-limiting step in steroidogenesis. Steroid hormone biosynthesis and
      steroidogenic gene expression are regulated by LH, which activates various
      signaling pathways and transcription factors, including cAMP/Ca(2+)/CAMK
      (Ca(2+)/calmodulin-dependent kinase)-myocyte enhancer factor 2 (MEF2). The 4 MEF2
      transcription factors are essential regulators of cell differentiation and
      organogenesis in numerous tissues. Recently, MEF2 was identified in Sertoli and
      Leydig cells of the testis. Here, we report that MEF2 regulates steroidogenesis
      in mouse MA-10 Leydig cells by acting on the Star gene. In MA-10 cells depleted
      of MEF2 using siRNAs (small interfering RNAs), STAR protein levels, Star mRNA
      levels, and promoter activity were significantly decreased. On its own, MEF2 did
      not activate the mouse Star promoter but was found to cooperate with
      forskolin/cAMP. By chromatin immunoprecipitation and DNA precipitation assays, we
      confirmed MEF2 binding to a consensus element located at -232 bp of the Star
      promoter. Mutation or deletion of the MEF2 element reduced but did not abrogate
      the MEF2/cAMP cooperation, indicating that MEF2 cooperates with other DNA-bound
      transcription factor(s). We identified GATA4 (GATA binding protein 4) as a
      partner for MEF2 in Leydig cells, because mutation of the GATA element abrogated
      the MEF2/cAMP cooperation on a reporter lacking a MEF2 element. MEF2 and GATA4
      interact as revealed by coimmunoprecipitation, and MEF2 and GATA4
      transcriptionally cooperate on the Star promoter. Altogether, our results define
      MEF2 as a novel regulator of steroidogenesis and Star transcription in Leydig
      cells and identify GATA4 as a key partner for MEF2-mediated action. 

PMID- 25860032
TI  - Absence of Female-Typical Pheromone-Induced Hypothalamic Neural Responses and
      Kisspeptin Neuronal Activity in alpha-Fetoprotein Knockout Female Mice.
AB  - Pheromones induce sexually dimorphic neuroendocrine responses, such as LH
      secretion. However, the neuronal network by which pheromones are converted into
      signals that will initiate and modulate endocrine changes remains unclear. We
      asked whether 2 sexually dimorphic populations in the anteroventral
      periventricular and periventricular nuclei that express kisspeptin and tyrosine
      hydroxylase (TH) are potential candidates that will transduce the olfactory
      signal to the neuroendocrine system. Furthermore, we assessed whether this
      transduction is sensitive to perinatal actions of estradiol by using female mice
      deficient in alpha-fetoprotein (AfpKO), which lack the protective actions of Afp
      against maternal estradiol. Wild-type (WT) and AfpKO male and female mice were
      exposed to same- versus opposite-sex odors and the expression of Fos (the protein
      product of the immediate early gene c-Fos) was analyzed along the olfactory
      projection pathways as well as whether kisspeptin, TH, and GnRH neurons are
      responsive to opposite-sex odors. Male odors induced a female-typical Fos
      expression in target forebrain sites of olfactory inputs involved in reproduction
      in WT, but not in AfpKO females, whereas female odors induced a male-typical Fos
      expression in males of both genotypes. In WT females, opposite-sex odors induced
      Fos in kisspeptin and TH neurons, whereas in AfpKO females and WT males, only a
      lower, but still significant, Fos expression was observed in TH but not in
      kisspeptin neurons. Finally, opposite-sex odors did not induce any significant
      Fos expression in GnRH neurons of both sexes or genotypes. Our results strongly
      suggest a role for fetal estrogen in the sexual differentiation of neural
      responses to sex-related olfactory cues. 

PMID- 25860033
TI  - Deleting the Redundant TSH Receptor C-Peptide Region Permits Generation of the
      Conformationally Intact Extracellular Domain by Insect Cells.
AB  - The TSH receptor (TSHR) extracellular domain (ECD) comprises a N-terminal leucine
      rich repeat domain and an hinge region (HR), the latter contributing to ligand
      binding and critical for receptor activation. The crystal structure of the
      leucine-rich repeat domain component has been solved, but previous attempts to
      generate conformationally intact complete ECD or the isolated HR component for
      structural analysis have failed. The TSHR HR contains a C-peptide segment that is
      removed during spontaneous TSHR intramolecular cleavage into disulfide linked A-
      and B-subunits. We hypothesized that deletion of the redundant C-peptide would
      overcome the obstacle to generating conformationally intact TSHR ECD protein.
      Indeed, lacking the C-peptide region, the TSHR ECD (termed ECD-D1) and the
      isolated HR (termed HR-D1) were secreted into medium of insect cells infected
      with baculoviruses coding for these modified proteins. The identities of TSHR ECD
      D1 and HR-D1 were confirmed by ELISA and immunoblotting using TSHR-specific
      monoclonal antibodies. The TSHR-ECD-D1 in conditioned medium was folded
      correctly, as demonstrated by its ability to inhibit radiolabeled TSH binding to
      the TSH holoreceptor. The TSHR ECD-D1 purification was accomplished in a single
      step using a TSHR monoclonal antibody affinity column, whereas the HR-D1 required
      a multistep protocol with a low yield. In conclusion, we report a novel approach
      to generate the TSHR ECD, as well as the isolated HR in insect cells, the former
      in sufficient amounts for structural studies. However, such studies will require
      previous complexing of the ECD with a ligand such as TSH or a thyroid-stimulating
      antibody. 

PMID- 25860034
TI  - Lowering radiation dose during dedicated colorectal cancer MDCT: comparison of
      low tube voltage and sinogram-affirmed iterative reconstruction at 80 kVp versus
      blended dual-energy images in a population of patients with low body mass index.
AB  - PURPOSE: To assess the diagnostic accuracy, cancer staging, image quality, and
      radiation dose of 80-kVp computed tomography (CT) images for patients with
      colorectal cancers (CRCs) using sinogram-affirmed iterative reconstruction
      (SAFIRE). METHODS: Sixty-four consecutive patients (mean weight 62.5  +/-  11.3
      kg, mean BMI 24.1  +/-  3.3 kg/m(2)) with known CRC underwent dual-energy CT.
      Data were reconstructed as a weighted average (WA) 120-kVp dataset. Both filtered
      back projection (FBP) and SAFIRE were applied to reconstruct the WA 120-Kvp
      (Protocol A, B) and 80-kVp (Protocol C, D) image sets. The image noise, signal-to
      noise ratio (SNR), and contrast-to-noise ratio (CNR) of the cancers, the normal
      reference tissues, and the effective dose for each protocol were assessed. The
      cancer detection, staging, and image quality were evaluated. Analysis of variance
      was used for statistical analysis. RESULTS: Compared with the FBP datasets at WA
      120-kVp (Protocol A) and 80-kVp (Protocol C), the SAFIRE-reconstructed images
      (Protocols B, D) demonstrated significantly lower image noise (P  <  0.0083).
      Protocol D yielded significantly higher CNRs and SNRs for the CRCs and normal
      reference tissues than did Protocols A and C (P  <  0.0083). Protocol D also
      exhibited a significantly higher CNR for the CRC and some normal reference
      tissues than did Protocol B (P  <  0.0083). For hypovascular liver metastases (n 
      =  10), Protocol D yielded better SNRs and significantly higher CNRs than did
      Protocol A (P  <  0.0083). Overall, accuracy for tumor staging and liver
      metastasis was 95.3% (61/64) and 100%, respectively, in all of the 4 protocols.
      The mean effective dose decreased 41% from the WA 120-kVp to the 80-kVp protocols
      (6.23 vs. 3.68 mSv). CONCLUSIONS: The 80-kVp technique with SAFIRE provided high
      SNR, high CNR, and good accuracy for staging in nonobese patients with CRC. Our
      study results should be extrapolated to patient populations with a high BMI with
      caution. Further studies of high BMI patients are therefore warranted.

PMID- 25860035
TI  - [Inpatient cutaneous adverse reactions to systemic antibiotics: an analytical
      cross-sectional retrospective study].
AB  - INTRODUCTION: The reported literature about the types of cutaneous adverse
      antibiotic reactions (ATB-CAR) and the responsible antimicrobial class is scarce.
      AIM: to describe the clinical and histopathological profile of these reactions,
      and potential associations between different types of ATB-CAR and causal
      antibiotic class in a tertiary hospital in Chile. MATERIAL AND METHODS: Cross
      sectional retrospective study performed at the Hospital of the Pontificia
      Universidad Catolica de Chile. RESULTS: A total of 58 patients were included. The
      most common type of ATB-CAR was morbilliform (n: 37, 63.8%). The antibiotics most
      frequently involved were the penicillins and cephalosporins (n: 34, 69.3%). The
      most common histological pattern in all types of ATB-CAR was superficial
      perivascular dermatitis with or without spongiosis. There was significant
      association between urticarial, morbilliform, DRESS and PEGA types, with the use
      of penicillins, cephalosporins, cotrimoxazole, and lincomycin, respectively (n:
      4,100%, n: 15, 40.5%, n: 2; 50%, n: 1, 50%, p < 0.05, respectively). DISCUSSION:
      This is the first description of the ATB-CAR patterns in South American
      hospitalized patients. Both clinical and histopathological patterns of ATB-CAR
      are similar to other published series, however the types of causal antibiotics
      are different.

PMID- 25860037
TI  - [Risk groups for tuberculosis in Chile].
AB  - Tuberculosis (TB) remains a major global and national problem. In Chile the
      incidence rate has remained at 13 per 100,000 inhabitants for several years
      without tendency to the expected decline that would allow their elimination by
      2020. As a low prevalence country, TB cases have been concentrated in risk
      groups, reaching 33% in 2013, and this proportion increases as younger people are
      analyzed. The main risk groups in Chile are HIV co-infection, foreigners and
      population of prisons. By 2013, the proportion of cases for these three groups
      was 8.7%, 8.4% and 3.9% respectively, and these percentages vary significantly
      when regional situation is analyzed. In addition, many of these patients have
      more than one risk factor, demons-rating the existence of clusters more
      vulnerable to TB. 

PMID- 25860039
TI  - [Microbiological features and risk factors for acquiring multidrug-resistant
      Acinetobacter baumannii bacteremia in pediatric patients. Case-control study].
AB  - BACKGROUND: Multidrug-resistant Acinetobacter baumannii (MAB) is an important
      nosocomial pathogen. OBJECTIVES: To analyze the risk factors for acquiring MAB,
      and the clinical and microbiological characteristics of MAB bacteremia (MABB) in
      children. MATERIALS AND METHODS: Control-case study 2005-2008. Demographic and
      clinical data from all MABB and from non-multiresistant gram-negative bacteremias
      were recorded. Identification at species level, antimicrobial susceptibility
      tests, time-kill studies and clonally relationships were performed. Stata 8.0 was
      used for data analysis. RESULTS: A total of 50 MABB and 100 controls were
      included. Ninety four percent of patients acquired MAB in ICU and the 88% had
      underlying diseases. All patients had invasive procedures previous to MABB. The
      median of hospitalization stay previous to MABB was different in cases than in
      controls (16 vs 7 days, p < 0.001). Five clones were detected among the MABB.
      Time-killing curves showed bactericidal activity of ampicillin/sulbactam plus
      gentamicin and polymixin B. Three patients with MAB died. In a multivariate
      analysis final predictors of MABB were: previous use of broad-spectrum
      antibiotics [OR: 7,0; IC 95% 1,93-25,0; p: 0,003] and mechanical ventilation [OR:
      4,19; IC 95% 1,66-10,0; p: 0,002]. CONCLUSIONS: MABB were detected in patients
      with underlying conditions, invasive procedures and prolonged hospitalization.
      Predictors of MABB were mechanical previous use of broad-spectrum antibiotics and
      mechanical ventilation.

PMID- 25860040
TI  - [Nosocomial infections impact in a hospital in Bogota, Colombia: effects on
      mortality and hospital costs].
AB  - BACKGROUND: Nosocomial infections (NI) are events associated with high impact on
      hospital costs and mortality. AIM: To evaluate from the health provider's
      perspective the costs and mortality attributable to NI. METHODS: We selected a
      sample of patients with and without NI matched by age and diagnosis at admission.
      Costs were calculated and converted from Colombian pesos to US dollars using the
      average exchange rate of 2008. We evaluated the mortality rate in both groups.
      RESULTS: We collected data on 187 patients with NI and 276 without NI. Median
      total hospitalization cost was US$ 6,329 (95% CI US$5,527-7,934) in NI patients,
      while in non-infected patients this median was US$1,207 (95% CI US$ 974-1,495).
      Mortality was higher in the NI group (31.6% versus 5.1%). Patients with NI had
      longer hospital stays (median 21 days, 95% CI 18-24 days) than non-infected
      patients (median 5 days, 95% CI 5-6 days). Mortality was also markedly higher in
      the NI group than in the non-infected group (31.6% versus 5.1%). CONCLUSION: NI
      are adverse and costly events related to patient attention that affect adversely
      the quality of attention.

PMID- 25860041
TI  - [Vaginal infections in a Family Health Clinic in the Metropolitan Region, Chile].
AB  - BACKGROUND: Vaginal infections are a frequent cause for consultation, but their
      prevalence and etiology vary in different populations. OBJECTIVES: To determine
      the prevalence and etiologies of vaginal infection in women attending a family
      health center in the Metropolitan Region of Chile. METHODS: The microbiological
      diagnosis was made by wet mount and Gram stain. Diagnosis of trichomoniasis was
      performed by wet mount, culture and polymerase chain reaction. RESULTS: 101 women
      aged 15-54, not selected by signs or symptoms of vaginal infection, 46 of them
      pregnant were included. In 47 women (46.5%), vaginal infections were diagnosed.
      An association was observed between age and frequency of vaginal infection. The
      proportion of infections among pregnant and non-pregnant women was similar. The
      most frequent infections were bacterial vaginosis (16.8%), vulvovaginal
      candidiasis (11.9%) and co-infections (6.9%). We found 5.9% of intermediate
      microbiota cases, 3% of trichomoniasis and 2% of aerobic vaginitis. Symptoms of
      vaginal infection had poor agreement with microbiological findings. Otherwise
      physical signs had good agreement with the presence of infection, but low to
      moderate concordance with a specific etiology. CONCLUSIONS: We found a high
      prevalence of vaginal infections in the study population. It is necessary to
      improve the definitions and criteria of microbiological diagnosis of co
      infections and intermediate microbiota, for them to be diagnosed in the clinical
      practice. More descriptive questionnaires are recommended to enhance the
      usefulness of clinical examination.

PMID- 25860042
TI  - [Demodex spp in chronic blepharitis patients].
AB  - BACKGROUND: Blepharitis is a very common disease in the ophthalmologic practice
      generally taking a chronic course with intermittent exacerbations. Several
      studies have linked the presence of Demodex folliculorum with chronic
      blepharitis, since the mite has the capacity to perpetuate the follicular
      inflammatory process. The prevalence of infection by Demodex spp. is variable
      depending on the population. In Paraguay, information on the frequency of the
      infestation in patients with chronic blepharitis is not available. AIM: To
      determine the frequency of Demodex spp, and the ocular microbiota in patients
      with chronic blepharitis attending the Department of Ophthalmology at the
      Teaching Hospital of the National University of Asuncion. PATIENTS AND METHODS:
      Consecutively, 28 patients with chronic blepharitis, who agreed to participate in
      the study, were included. Eyes lashes from the upper and lower eyelids were
      extracted for immediate mite search by direct observation under a light
      microscope. Samples from eyelids were taken with Kimura spatula and then cultured
      on blood agar and in enrichment media and incubated in 5% CO2 at 35 degrees  C
      for 72 hours. RESULTS: Among participants, females were more frequent (64%), the
      age ranged from 17 to 87 years (mean: 38.0; SD: +/- 13.5 years). The prevalence
      of Demodex sp was 54%. Bacteria were isolated 92.9% of cases, most frequently
      coagulase-negative staphylococci (75%). No association was found between socio
      demographic or clinical characteristics and the presence of Demodex sp.
      CONCLUSION: The observed high prevalence of infestation by Demodex spp in
      patients with chronic blepharitis is consistent with other studies.

PMID- 25860044
TI  - [Post surgery morbidity in patients with complicated hepatic hydatidosis].
AB  - INTRODUCTION: Hepatic echinococcosis (HE) surgery is common in southern's Chile
      hospitals; however, related publications are scarce and with conflicting results,
      especially with regard to postoperative morbidity (POM), due to the diversity in
      it severity. The aim of this study is to determine POM in patients undergoing
      surgery for complicated HE (CHE). MATERIAL AND METHODS: Case series part of a
      prospective cohort. Patients undergoing surgery for CHH in hospitals Hernan
      Henriquez Aravena hospital and Clinica Mayor of Temuco, between 2000 and 2012
      were included. The main outcome variable was development of POM using the Clavien
      scale. Other variables of interest were hospital stay, mortality and recurrence.
      Descriptive statistics were applied and incidence of POM was determined. RESULTS:
      73 patients with a median age of 41 years and 58.9% female were studied. The
      median ultrasound diameter cysts were 15.0 cm. The average surgical time was
      125.4 +/- 26.3 min. The surgical procedure used most often was the pericystectomy
      (84.9%); and 84.9% of cases was performed concomitantly some other surgical
      procedure. The incidence of POM was 19.2%, 78.6% of whose cases were Grade I or
      II Clavien. The aetiology was 10.9% of medical complications and 8.2% of surgical
      complications. 1.4% of mortality was recorded; and with a median follow up of 97
      months, no recurrence was verified. CONCLUSIONS: POM in a cohort of patients with
      CHE is lower than the published and low severity. Subgroups with higher POM were:
      patients with coexistence of more than one complication, those with
      colangiohydatidosis and patients with liver abscess of hydatid origin.

PMID- 25860045
TI  - [Pharmacotherapy follow-up of Chilean inpatients with HIV/AIDS in a high
      complexity hospital during one year].
AB  - BACKGROUND: Pharmaceutical follow-up consists on the detection, prevention, and
      resolution of drug-related problems (DRP) in a continuous, systematized, and
      documented way. DRP is a health problem connected to pharmacotherapy, which can
      interfere with the expected health outcomes in the patient. AIM: To make a
      pharmacotherapeutic surveillance in HIV/AIDS inpatients attended at "Hospital San
      Juan de Dios" throughout a year prospective study (January to December 2012).
      RESULTS: 88.6% (93/105) of patients were in stage AIDS with a median of CD4+
      lymphocytes of 29 cells/mm3 and a viral load of 107,000 RNA copies/mL. The 16.2%
      were admitted to a intensive care unit ICU. 296 DRP (DRP 2.8 per patient) were
      detected, 72% of DRP (n; 213) were associated with treatment safety, 94 were
      adverse reactions, 19 required dose adjustments, and 6 interactions had a
      negative clinical impact; 23.3% (n: 69) experimented the necessity to add or
      remove a drug and 4.7% (n: 14) presented problems associated with effectiveness.
      A statistically significant relation was observed when associating the number of
      DRP with admittance to the ICU and the use of more than six drugs. CONCLUSION:
      The results allow the conclusion that inpatients present drug-related problems
      mainly related to toxicity, becoming risk factors for the development of them
      admittance to ICU, and concomitant use of more than 6 drugs.

PMID- 25860047
TI  - [Immune evasion by herpes simplex viruses].
AB  - Herpes simplex viruses and humans have co-existed for tens of thousands of years.
      This long relationship has translated into the evolution and selection of viral
      determinants to evade the host immune response and reciprocally the evolution and
      selection of host immune components for limiting virus infection and damage.
      Currently there are no vaccines available to avoid infection with these viruses
      or therapies to cure them. Herpes simplex viruses are neurotropic and reside
      latently in neurons at the trigeminal and dorsal root ganglia, occasionally
      reactivating. Most viral recurrences are subclinical and thus, unnoticed. Here,
      we discuss the initial steps of infection by herpes simplex viruses and the
      molecular mechanisms they have developed to evade innate and adaptive immunity. A
      better understanding of the molecular mechanisms evolved by these viruses to
      evade host immunity should help us envision novel vaccine strategies and
      therapies that limit infection and dissemination. 

PMID- 25860048
TI  - [Malassezia pachydermatis (Weidman) C.W. Dodge].

PMID- 25860049
TI  - [Cryptococcal infections in non-HIV infected patients: a new clinical problem in
      Chile].
AB  - Cryptococcal infections are classically associated to HIV/AIDS patients without
      therapy, but its presence among other immunosuppressed patients is less
      recognized. We report 3 lethal cases in non HIV-patients. Two of them presented
      with meningitis associated to renal transplant or corticosteroid use and, the
      third, with a necrotic skin infection in the context of progressive liver
      cirrhosis. In the former two patients, meningeal infection was suspected late,
      and in the latter, the diagnosis was established postmortem. Cryptococcal
      infections in non-HIV immunosupressed patients can affect different sites, are
      suspected late and have a high case-fatality ratio. 

PMID- 25860050
TI  - [Atypical mycobacterial infections in five adult patients without evidence of
      immunosuppression. Making an experience].
AB  - We aim to communicate the experience gathered during the management of infections
      by atypical mycobacteria in immunocompetent patients in a general practice.
      Between 2008 and 2013, 5 patients with non-tuberculous mycobacterial infections
      were identified: 2 with cutaneous involvement and 3 with lung infection. None of
      them had evidence of immunosuppression. A patient with elbow bursitis by M.
      chelonae presented with a high mononuclear count in fluid analysis with
      mycobacterial growth at the fifth day of culture. He evolved satisfactorily with
      clarithromycin. A case with M. fortuitum skin infection had a delayed initial
      diagnosis with progression to local draining lymph nodes; the culture when
      requested was positive after 13 days of incubation. Patients with pulmonary
      infection presented with prolonged cough and sputum and had in common to be
      postmenopausal women displaying small nodules and bronchiectases at lung images,
      a classical pattern. Time elapsed between respiratory sampling and a definitive
      inform ranged from 40 to 89 days. Non-tuberculous mycobacterial infections in non
      immunosuppresed patients can generate diagnostic and therapeutic challenges.
      Delay in identification contributes to this problem. 

PMID- 25860052
TI  - [Penicillin production in Chile between 1944 and 1954].
AB  - Penicillin production in Chile was a pioneering development; however there is not
      much information to learn about it. The Chilean Institute for Bacteriology
      (Instituto Bacteriologico de Chile) produced penicillin between 1944 and 1973.
      The stage starting in 1953 is better known since there was an agreement with
      United Nations. Our research focused on building a story about production between
      1944 and 1954 based on archival information and the national and international
      historic context. Our results place Chile amongst the pioneer countries in the
      successful industrialization of the drug. Our conclusions are that this was a
      proper industrial production as opposite to a pilot plant - a name commonly used
      to call the early factory. We explain the production plant trajectory by making
      relations between technological change and governance. Finally, we believe the
      later expansion of the plant, in the context of the agreement with the United
      Nations, took place under unpromising governance conditions, which called for
      passive innovation and technology management. 

PMID- 25860053
TI  - [Sepsis in children with cancer: problems to detect it and challenges for
      diminishing it].
AB  - Since 1992 the availability of the criteria of systemic inflammatory response
      syndrome (SIRS) has improved the identification of subjects with sepsis. Sepsis
      remains a major hospital complication worldwide, responsible for thousands of
      deaths in children with cancer. Different biomarkers have been proposed for
      discrimination of septic child, who is not, but its introduction and routine use
      in control programs and surveillance has not been possible so far. The challenge
      in septic cancer remains valid subject and makes it a public health problem. The
      research accompanying the treatment of these children and introducing them,
      depend on their effectiveness, financing and universal availability of methods;
      but especially strategic planning based on that knowledge. 

PMID- 25860054
TI  - [Pott's disease and immunological diagnosis of tuberculosis, about a pediatric
      clinical case].
AB  - Tuberculosis (TB) remains a major health problem in the world. The clinical forms
      of TB in children are variable, pulmonary involvement occurs in two thirds of
      cases. In the remaining third, clinical forms incluye node, meningeal and
      osteoarticular involvement. CASE REPORT: 7 year old boy with a history of an
      osteolytic lesion of the right ischial branch. Three months later he presented
      with spondylodiscitis at L2-L3, associated with a large abscess in the right
      iliac psoas muscle. Pott's disease was suspected, and tuberculin test and T
      SPOT(r).TB test were performed, with a positive result. Antimicrobial treatment
      was initiated with isoniazid, rifampicin, pyrazinamide and ethambutol. After 30
      days, Mycobacterium tuberculosis was isolated from psoas abscess. We discuss
      methods of TB diagnosis, with special emphasis on immunological methods:
      tuberculin test and interferon-gamma release assays. Methods of immunological TB
      diagnosis are an important contribution to the diagnosis of this disease,
      allowing early initiation of treatment.

PMID- 25860055
TI  - [Detection of flavivirus in mosquitoes (Diptera: Culicidae) from Easter Island
      Chile].
AB  - Flaviviruses are arthropod-borne viruses, mainly by mosquitoes of the genera
      Aedes and Culex (Culicidae) that are detected in tropical and subtropical areas.
      Main flaviviruses of public health importance are: dengue, West Nile virus,
      yellow fever, among others. In continental Chile, flaviviruses has not been
      detected. However, there are indigenous cases of dengue detected in Easter Island
      since 2002, as the presence of its vector Aedes aegypti. The aim of this study
      was: To determine diversity of flavivirus mosquitoes present in Easter Island.
      Thirty pools of mosquitoes collected in Hanga Roa were analyzed; a RT-PCR nested
      flavivirus was performed. Thirteen positive samples were detected and the
      amplification products were sequenced, identifying two specific flavivirus
      Insect, the Cell fusing agent virus and other related viruses Kamiti River. This
      is the first study in Chile showed the presence of flavivirus in vectors in
      Easter Island. 

PMID- 25860056
TI  - [Utility of Aspergillus-LFD: first experience in Chile].
AB  - The diagnosis of invasive aspergillosis remains a challenge. Detection of
      galactomannan in serum and bronchoalveolar lavage is a useful tool; however due
      to methodological and economic reasons, the test frequencies of galactomannan
      assays vary from daily to weekly, which constitute a risk to the patient. In this
      study, we aimed to evaluate and correlate the performance of the new kit
      Aspergillus-LFD with the GM-EIA. Aspergillus-LFD kit represents a fast,
      economical and simple test; showed a good performance and excellent correlation
      with GM-EIA kit. Given the above, the Aspergillus-LFD is emerging as an
      alternative to consider in the early diagnosis of invasive aspergillosis. 

PMID- 25860057
TI  - [Rapid identification of pathogens from pediatric blood cultures by use of the
      FilmArray blood culture identification panel].

PMID- 25860058
TI  - Synergistic effects of surface chemistry and topologic structure from modified
      microarc oxidation coatings on Ti implants for improving osseointegration.
AB  - Microarc oxidation (MAO) coating containing Ca, P, Si, and Na elements on a
      titanium (Ti) implant has been steam-hydrothermally treated and further mediated
      by post-heat treatment to overcome the compromised bone-implant integration. The
      bone regeneration, bone-implant contact, and biomechanical push-out force of the
      modified Ti implants are discussed thoroughly in this work. The best in vivo
      performances for the steam-hydrothermally treated one is attributed to the
      synergistic effects of surface chemistry and topologic structure. Through post
      heat treatment, we can decouple the effects of surface chemistry and the
      nanoscale topologic structure easily. Attributed to the excellent in vivo
      performance of the surface-modified Ti implant, the steam-hydrothermal treatment
      could be a promising strategy to improve the osseointegration of the MAO coating
      covered Ti implant. 

PMID- 25860059
TI  - Editorial: immunotherapy in central nervous system.

PMID- 25860060
TI  - New developments of clinical trial in immunotherapy for Alzheimer's disease.
AB  - Active or passive immunotherapy is expected to slow or stop the pathological
      process of Alzheimer's disease (AD). Immunotherapy for AD has demonstrated that
      targeting beta-amyloid (Abeta) or tau protein with vaccines or antibodies can
      reduce AD pathologies. Active anti-Abeta immunization for AD includes using
      AN1792 and second generation vaccines such as ACC-001, CAD106 and AFFITOPE
      vaccines, while antibodies for passive immunization include monoclonal antibodies
      and intravenous immunoglobulin (IVIG). Preclinical trials have shown powerful
      evidence of significant advances for more than a decade; however, there are still
      issues that need to be addressed in clinical trials. In the phase IIa AN1792
      trial, 6% of patients who received the vaccination were diagnosed with
      meningoencephalitis as an adverse effect. There was a high incidence of amyloid
      related imaging abnormalities (ARIA) in patients treated with some monoclonal
      antibodies. Moreover, several phase 3 clinical trial findings of immunization
      targeting Abeta were negative. These issues require attention in order to improve
      the safety and efficacy of immunization strategies in AD. Prevention studies and
      other novel immunization strategies have the potential to dramatically impact AD
      care. Herein we review the recent advances in clinical trials involving
      immunotherapy for AD. 

PMID- 25860061
TI  - Immunotherapy strategies for spinal cord injury.
AB  - Regeneration in the central nervous system (CNS) of adult mammalian after
      traumatic injury is limited, which often causes permanent functional motor and
      sensory loss. After spinal cord injury (SCI), the lack of regeneration is mainly
      attributed to the presence of a hostile microenvironment, glial scarring, and
      cavitation. Besides, inflammation has also been proved to play a crucial role in
      secondary degeneration following SCI. The more prominent treatment strategies in
      experimental models focus mainly on drugs and cell therapies, however, only a few
      strategies applied in clinical studies and therapies still have only limited
      effects on the repair of SCI. Recently, the interests in immunotherapy strategies
      for CNS are increasing in number and breadth. Immunotherapy strategies have made
      good progresses in treating many CNS degenerative disorders, such as Alzheimer's
      disease (AD), Parkinson's disease (PD), stroke, and multiple sclerosis (MS).
      However, the strategies begin to be considered to the treatment of SCI and other
      neurological disorders in recent years. Besides anti-inflamatory therapy,
      immunization with protein vaccines and DNA vaccines has emerged as a novel
      therapy strategy because of the simplicity of preparation and application. An
      inflammatory response followed by spinal cord injury, and is controled by
      specific signaling molecules, such as some cytokines playing a crucial role. As a
      result, appropriate immunoregulation, the expression of pro-inflammatory
      cytokines and anti-inflammatory cytokines may be an effective therapy strategy
      for earlier injury of spinal cord. In addition, myelinassociated inhibitors
      (MAIs) in the injured spinal cord, such as Nogo, myelin-associated glycoprotein
      (MAG) and oligodendrocyte- myelin glycoprotein (OMgp) are known to prevent axonal
      regeneration through their co-receptors, and to trigger demyelinating
      autoimmunity through T cell-mediated harmful autoimmune response. The antagonism
      of the MAIs through vaccinating with protein or DNA vaccines targeting Nogo, MAG,
      OMgp, and their co-receptors, may be an effective strategy for the treatment of
      SCI. However, immunotherapy such as anti-inflammtory therapy or vaccine targeting
      MAIs or their receptors, accompanied with the potential in risking autoimmune
      diseases. As a result, in order to optimize the anti-inflammtory therapy and
      design of protein or DNA vaccines for their use in the future clinical
      application, we need to further understand the possible mechanisms of
      neuroprotective immunity. This review presents recent advances in the development
      of immunotherapy strategies for the treatment of axonal degeneration and
      demyelination, and improvement of motor function after SCI. 

PMID- 25860062
TI  - Gymnema sylvestre R. Br., an Indian medicinal herb: traditional uses, chemical
      composition, and biological activity.
AB  - Gymnema sylvestre R. Br. is one of the most important medicinal plants that grows
      in tropical forests in India and South East Asia. Its active ingredients and
      extracts of leaves and roots are used in traditional medicine to treat various
      ailments and they are present in the market for pharmaceutical and
      parapharmaceutical products. Commercial products based on substances of plant
      origin that are generally connoted as natural have to be subjected to monitoring
      and evaluation by health authorities for their potential impacts on public
      health. The monitoring and evaluation of these products are critical because the
      boundary between a therapeutic action and a functional or healthy activity has
      not yet been defined in a clear and unambiguous way. Therefore, these products
      are considered borderline products, and they require careful and rigorous
      studies, in order to use them as complement and/or even replacement of synthetic
      drugs that are characterized by side effects and high economic costs. This review
      explores the traditional uses, chemical composition and biological activity of G.
      sylvestre extracts, providing a general framework on the most interesting
      extracts and what are the necessary studies for a complete definition of the
      range of activities. 

PMID- 25860063
TI  - Mechanisms of enhanced vasoconstriction in the mouse model of atherosclerosis:
      the beneficial effects of sildenafil.
AB  - Sildenafil ameliorates aortic relaxations in apolipoprotein E knockout (apoE)
      mice. Now, we tested the hypothesis that endothelial dysfunction (ED) in this
      model is characterized by contractile hyperresponsiveness to phenylephrine (PE)
      and that this abnormality may be repaired using sildenafil. The aortic rings were
      evaluated in apoE mice treated with sildenafil (apoE-sil, 40 mg/kg/day) and
      compared with apoE and wild-type (WT) mice administered with vehicle (veh). The
      apoE-veh mice exhibited an imbalance of nitric oxide and reactive oxygen species
      (NO/ROS) levels and an increased maximum response (Rmax, 20%) and sensitivity
      (7%) to PE, which were not modified by endothelial removal. Under the prostanoids
      blockade, vasocontraction was decreased more in apoE-veh (-37%) than in WT (-27%)
      and apoE-sil (-30%) mice. NADPH-oxidase blockade abolished the enhanced
      contractile responsiveness in apoE-veh (-33%), without effects in WT and apoE-sil
      groups. The atherosclerotic lesions and the imbalance of NO/ROS were reduced
      (40%) in apoE-sil mice. In conclusion, ED in apoE mice was characterized by
      decreased NO-bioavailability and contractile hyperresponsiveness, due to
      thromboxane and oxidative stress, and was normalized by sildenafil. The
      beneficial effects of this phosphodiesterase-5 inhibitor on ED and lipid
      deposition provide new insights for its use as adjuvant in the treatment of
      atherosclerosis. 

PMID- 25860064
TI  - Targeting chromatin remodeling to prevent cardiovascular disease in diabetes.
AB  - Diabetes is a major cause of cardiovascular morbidity and mortality and its
      prevalence is rapidly increasing worldwide. Despite clear advances in developing
      effective glucose-lowering drugs, clinical trials have recently shown that
      intensive glycemic control failed to reduce cardiovascular events in the diabetic
      population. These findings support the concept that the hyperglycemic environment
      may be remembered in the cardiovascular system. This phenomenon has been recently
      defined as "metabolic memory" and may contribute to explain the progression of
      diabetic vascular complications despite achievement of target HbA1c levels. In
      this regard, epigenetic changes of DNA/histone complexes are emerging as
      important modulators of oxidant and inflammatory genes, thus leading to
      persistent cardiac and vascular dysfunction. Over the last few years, the rapid
      development of many compounds (i.e. histone deacetylase and histone
      acetyltransferase inhibitors) able to erase adverse chromatin signatures led to
      the perception that reverting hyperglycemic damage might be possible and
      represents an attractive challenge. Here we critically discuss recent evidence
      supporting the concept that chromatin alterations are key drivers of
      cardiovascular disease and describe the emerging potential of chromatin modifying
      agents for the reprogramming of detrimental epigenetic signatures in patients
      with cardiometabolic disturbances. 

PMID- 25860065
TI  - Flavonoids rich fraction of Citrus limetta fruit peels reduces proinflammatory
      cytokine production and attenuates malaria pathogenesis.
AB  - Exploration of possible pharmacological effects along with characterisation of
      the bioactive compounds present in peels may have a key role in converting the
      fruit waste materials into therapeutic value added products. Extracts prepared
      from the Citrus limetta fruit peels were studied for antioxidant and anti-
      inflammatory activity using in-vitro bioassays. Among all, ClEt an ethanol
      extract of Citrus limetta fruit peels has shown promising anti-oxidant and anti
      inflammatory activity. ClEt was further validated to ensure its safety evaluation
      at 2000mg/kg and anti-malarial efficacy at 100, 250, 500 mg/kg body weight with
      special reference to inflammatory mediators involved in malaria pathogenesis. In
      vivo study revealed that ClEt was safe at higher dose and showed promising anti
      malarial activity by inhibiting the parasitaemia and inflammatory mediators (IFN
      gamma, TNF-alpha, IL-6) involved in malaria pathogenesis, able to improve the
      haemoglobin and glucose level and increase the survival time. Chemical
      fingerprint of ClEt revealed the presence of flavonoids. Results suggested the
      suitability of ClEt, a flavonoid rich fraction of Citrus limetta fruit peels as a
      candidate for further investigation towards the management of malaria
      pathogenesis. 

PMID- 25860066
TI  - Low doses of CPS49 and flavopiridol combination as potential treatment for
      advanced prostate cancer.
AB  - Prostate cancer (PCa) still ranks as the second most frequently diagnosed cancer
      and metastatic castration resistant prostate cancer (CRPC) is a foremost cause of
      men cancer death around the world. The aim of this work was to investigate the
      selectivity and efficacy of new drug combinations for CRPC. We combined three
      compounds: paclitaxel (PTX: taxane that inhibits microtubule polymerization); 2
      (2,4-Difluoro-phenyl)-4,5,6,7-tetrafluoro-1H-isoindole- 1,3(2H)-dione (CPS49;
      redox-reactive thalidomide analog with anti-angiogenic properties) and
      flavopiridol (flavo: semisynthetic flavonoid that inhibits cyclin dependent
      kinases). We assessed CPS49-flavo or -PTX combinations cytotoxicity in a panel of
      PCa cell lines and PC3 xenografts. We found that CPS49 enhanced flavo or PTX
      cytotoxicity in human PCa cell lines while showed resistance in a non-tumor cell
      line. Furthermore, xenografts generated by inoculation of human prostate
      carcinoma PC3 cells in nu/nu mice showed that CPS49/flavo administration reduced
      tumor growth both after 2 weeks of co-treatment and after 1 week of pretreatment
      with a low dose of flavo followed by 2 weeks of co-treatment. PTX and CPS49
      combination did not significantly reduce tumor growth in PC3 xenografts.
      Histological analysis of xenograft PC3 tumor samples from CPS49/flavo combination
      showed extensive areas of necrosis induced by the treatment. RT-qPCR array
      containing 23 genes from PC3 cells or PC3 xenografts exposed to CPS49/flavo
      combination showed that this treatment shut down the expression of several genes
      involved in adhesion, migration or invasion. In summary, the antitumor activity
      of CPS49 or flavopiridol was improved by the combination of these compounds and
      using half dose of that previously reported. Hence, CPS49-flavo combination is a
      promising new alternative for PCa therapy.

PMID- 25860067
TI  - Expression of CTB-10*rolGLP-1 in E. coli and its therapeutic effect on type 2
      diabetes.
AB  - Glucagon-like peptide-1 (GLP-1) is a short peptide that can significantly reduce
      blood glucose level. Recombination oral long-acting glucagon-like peptide-1
      (rolGLP-1), is a GLP-1 analog generated from site-specific mutation of GLP-1. CTB
      is a non-toxic portion of the cholera toxin and an ideal protein antigen carrier.
      In this study, we firstly constructed a vector pET-22b (+)-CTB-10*rolGLP-1 to
      express a fusion protein composed of CTB and ten tandem repeated rolGLP-1 in BL21
      (DE3) line of E. coli. The CTB-10*rolGLP-1 was expressed efficiently in the
      inclusion bodies. The expression product was analyzed by SDS-PAGE electrophoresis
      and Western blotting. The inclusion bodies were then denatured, refolded and
      purified by ion exchange chromatography to obtain a high-purity CTB- 10*rolGLP-1.
      The therapeutic effect of CTB-10*rolGLP-1 was assessed in comparison with
      10*rolGLP-1 alone by daily oral-gavage administration up to 10 days in
      streptozotocin-induced type 2 diabetic mice. The results showed that the level of
      blood glucose was reduced more effectively and the oral glucose tolerance of mice
      was improved more significantly with the administration of CTB-10*rolGLP-1. Our
      results provided a potentially promising oral biological drug for the treatment
      of type 2 diabetes. 

PMID- 25860068
TI  - Histomorphometric analysis of salivary gland in wistar rats treated chronically
      with two benzodiazepines.
AB  - Benzodiazepines (BZDs), the most commonly prescribed psychotropic drugs with
      anxiolytic action, may cause hyposalivation. Therefore, this study sought to
      quantify the acini (N) in parotid glands of Wistar rats treated chronically with
      two BZDs (Lorazepam and Midazolan) and to verify the action of the pilocarpine
      when administered with these drugs. Ninety male Wistar rats were distributed in 9
      groups according to the administration of: a) S30 - saline solution for 30 days;
      b) S60 - saline solution for 60 days; c) P60 - pilocarpine for 60 days; d) L30 -
      Lorazepam for 30 days; e) M30 - Midozolam for 30 days; f) LS60 - Lorazepam for 60
      days and, after this period, 30 more days of saline solution; g) MS60 - Midazolam
      for 30 days and, after this period, 30 more days of saline solution; h) LP60 -
      Lorazepam and Pilocarpine for 60 days; i) MP60 - Midazolam and Pilocarpine for 60
      days. A surgery was performed on the animals to remove the glands. After this,
      histological cuts were stained by hematoxylin and eosin, from which the N was
      quantified. The ANOVA and Games-Howell tests were used for statistical analysis.
      The L30 and M30 groups presented less N than did the S30 group (p<0.05). The
      LS60, MS60, and LP60 groups presented less N than did the S60 and P60 groups
      (p<0.05). No differences could be observed between the MP60 and S60 groups. The
      chronic administration of Midazolam and Lorazepam reduced acini, which may well
      have collaborated in the reduction of salivary flow previously verified. The
      association of Midazolam with Pilocarpine led to the reestablishment of acinar
      cells, which may have favored the restoration of the salivary flow formerly
      shown.

PMID- 25860069
TI  - An ultrasound-based liquid pressure measurement method in small diameter
      pipelines considering the installation and temperature.
AB  - Liquid pressure is a key parameter for detecting and judging faults in hydraulic
      mechanisms, but traditional measurement methods have many deficiencies. An
      effective non-intrusive method using an ultrasound-based technique to measure
      liquid pressure in small diameter (less than 15 mm) pipelines is presented in
      this paper. The proposed method is based on the principle that the transmission
      speed of an ultrasonic wave in a Kneser liquid correlates with liquid pressure.
      Liquid pressure was calculated using the variation of ultrasonic propagation time
      in a liquid under different pressures: 0 Pa and X Pa. In this research the time
      difference was obtained by an electrical processing approach and was accurately
      measured to the nanosecond level through a high-resolution time measurement
      module. Because installation differences and liquid temperatures could influence
      the measurement accuracy, a special type of circuit called automatic gain control
      (AGC) circuit and a new back propagation network (BPN) model accounting for
      liquid temperature were employed to improve the measurement results. The
      corresponding pressure values were finally obtained by utilizing the relationship
      between time difference, transient temperature and liquid pressure. An
      experimental pressure measurement platform was built and the experimental results
      confirm that the proposed method has good measurement accuracy. 

PMID- 25860070
TI  - A new method of using sensor arrays for gas leakage location based on correlation
      of the time-space domain of continuous ultrasound.
AB  - This paper proposes a time-space domain correlation-based method for gas leakage
      detection and location. It acquires the propagated signal on the skin of the
      plate by using a piezoelectric acoustic emission (AE) sensor array. The signal
      generated from the gas leakage hole (which diameter is less than 2 mm) is time
      continuous. By collecting and analyzing signals from different sensors' positions
      in the array, the correlation among those signals in the time-space domain can be
      achieved. Then, the directional relationship between the sensor array and the
      leakage source can be calculated. The method successfully solves the real-time
      orientation problem of continuous ultrasonic signals generated from leakage
      sources (the orientation time is about 15 s once), and acquires high accuracy
      location information of leakage sources by the combination of multiple sets of
      orientation results. According to the experimental results, the mean value of the
      location absolute error is 5.83 mm on a one square meter plate, and the maximum
      location error is generally within a +/-10 mm interval. Meanwhile, the error
      variance is less than 20.17. 

PMID- 25860071
TI  - Vineyard yield estimation based on the analysis of high resolution images
      obtained with artificial illumination at night.
AB  - This paper presents a method for vineyard yield estimation based on the analysis
      of high-resolution images obtained with artificial illumination at night. First,
      this paper assesses different pixel-based segmentation methods in order to detect
      reddish grapes: threshold based, Mahalanobis distance, Bayesian classifier,
      linear color model segmentation and histogram segmentation, in order to obtain
      the best estimation of the area of the clusters of grapes in this illumination
      conditions. The color spaces tested were the original RGB and the Hue-Saturation
      Value (HSV). The best segmentation method in the case of a non-occluded reddish
      table-grape variety was the threshold segmentation applied to the H layer, with
      an estimation error in the area of 13.55%, improved up to 10.01% by morphological
      filtering. Secondly, after segmentation, two procedures for yield estimation
      based on a previous calibration procedure have been proposed: (1) the number of
      pixels corresponding to a cluster of grapes is computed and converted directly
      into a yield estimate; and (2) the area of a cluster of grapes is converted into
      a volume by means of a solid of revolution, and this volume is converted into a
      yield estimate; the yield errors obtained were 16% and -17%, respectively. 

PMID- 25860072
TI  - Portable and reusable optofluidics-based biosensing platform for ultrasensitive
      detection of sulfadimidine in dairy products.
AB  - Sulfadimidine (SM2) is a highly toxic and ubiquitous pollutant which requires
      rapid, sensitive and portable detection method for environmental and food
      monitoring. Herein, the use for the detection of SM2 of a portable optofluidics
      based biosensing platform, which was used for the accurate detection of bisphenol
      A, atrazine and melamine, is reported for the first time. The proposed compact
      biosensing system combines the advantages of an evanescent wave immunosensor and
      microfluidic technology. Through the indirect competitive immunoassay, the
      detection limit of the proposed optofluidics-based biosensing platform for SM2
      reaches 0.05 MUg.L(-1) at the concentration of Cy5.5-labeled antibody of 0.1
      MUg.mL(-1). Linearity is obtained over a dynamic range from 0.17 MUg.L(-1) to
      10.73 MUg.L(-1). The surface of the fiber probe can be regenerated more than 300
      times by means of 0.5% sodium dodecyl sulfate solution (pH = 1.9) washes without
      losing sensitivity. This method, featuring high sensitivity, portability and
      acceptable reproducibility shows potential in the detection of SM2 in real milk
      and other dairy products.

PMID- 25860073
TI  - Cross-layer cluster-based energy-efficient protocol for wireless sensor networks.
AB  - Recent developments in electronics and wireless communications have enabled the
      improvement of low-power and low-cost wireless sensors networks (WSNs). One of
      the most important challenges in WSNs is to increase the network lifetime due to
      the limited energy capacity of the network nodes. Another major challenge in WSNs
      is the hot spots that emerge as locations under heavy traffic load. Nodes in such
      areas quickly drain energy resources, leading to disconnection in network
      services. In such an environment, cross-layer cluster-based energy-efficient
      algorithms (CCBE) can prolong the network lifetime and energy efficiency. CCBE is
      based on clustering the nodes to different hexagonal structures. A hexagonal
      cluster consists of cluster members (CMs) and a cluster head (CH). The CHs are
      selected from the CMs based on nodes near the optimal CH distance and the
      residual energy of the nodes. Additionally, the optimal CH distance that links to
      optimal energy consumption is derived. To balance the energy consumption and the
      traffic load in the network, the CHs are rotated among all CMs. In WSNs, energy
      is mostly consumed during transmission and reception. Transmission collisions can
      further decrease the energy efficiency. These collisions can be avoided by using
      a contention-free protocol during the transmission period. Additionally, the CH
      allocates slots to the CMs based on their residual energy to increase sleep time.
      Furthermore, the energy consumption of CH can be further reduced by data
      aggregation. In this paper, we propose a data aggregation level based on the
      residual energy of CH and a cost-aware decision scheme for the fusion of data.
      Performance results show that the CCBE scheme performs better in terms of network
      lifetime, energy consumption and throughput compared to low-energy adaptive
      clustering hierarchy (LEACH) and hybrid energy-efficient distributed clustering
      (HEED). 

PMID- 25860074
TI  - A method to accurately estimate the muscular torques of human wearing
      exoskeletons by torque sensors.
AB  - In exoskeletal robots, the quantification of the user's muscular effort is
      important to recognize the user's motion intentions and evaluate motor abilities.
      In this paper, we attempt to estimate users' muscular efforts accurately using
      joint torque sensor which contains the measurements of dynamic effect of human
      body such as the inertial, Coriolis, and gravitational torques as well as torque
      by active muscular effort. It is important to extract the dynamic effects of the
      user's limb accurately from the measured torque. The user's limb dynamics are
      formulated and a convenient method of identifying user-specific parameters is
      suggested for estimating the user's muscular torque in robotic exoskeletons.
      Experiments were carried out on a wheelchair-integrated lower limb exoskeleton,
      EXOwheel, which was equipped with torque sensors in the hip and knee joints. The
      proposed methods were evaluated by 10 healthy participants during body weight
      supported gait training. The experimental results show that the torque sensors
      are to estimate the muscular torque accurately in cases of relaxed and activated
      muscle conditions. 

PMID- 25860075
TI  - Synthesis of Five-, Six-, and Seven-Membered 1,3- and 1,4-Heterocyclic Compounds
      via Intramolecular Hydroalkoxylation/Hydrothioalkoxylation of
      Alkenols/Thioalkenols.
AB  - Intramolecular hydroalkoxylation/hydrothioalkoxylation of nitrogen-tethered
      alkenes and alcohols/thiols mediated by boron trifluoride etherate leads to five
      membered thiazolidine, six-membered 1,4-oxazines (morpholines) and tetrahydro-2H
      1,4-thiazines (thiomorpholines), and seven-membered 1,4-oxazepanes in good
      yields. 

PMID- 25860076
TI  - Quantitative methods for reconstructing tissue biomechanical properties in
      optical coherence elastography: a comparison study.
AB  - We present a systematic analysis of the accuracy of five different methods for
      extracting the biomechanical properties of soft samples using optical coherence
      elastography (OCE). OCE is an emerging noninvasive technique, which allows
      assessment of biomechanical properties of tissues with micrometer spatial
      resolution. However, in order to accurately extract biomechanical properties from
      OCE measurements, application of a proper mechanical model is required. In this
      study, we utilize tissue-mimicking phantoms with controlled elastic properties
      and investigate the feasibilities of four available methods for reconstructing
      elasticity (Young's modulus) based on OCE measurements of an air-pulse induced
      elastic wave. The approaches are based on the shear wave equation (SWE), the
      surface wave equation (SuWE), Rayleigh-Lamb frequency equation (RLFE), and finite
      element method (FEM), Elasticity values were compared with uniaxial mechanical
      testing. The results show that the RLFE and the FEM are more robust in
      quantitatively assessing elasticity than the other simplified models. This study
      provides a foundation and reference for reconstructing the biomechanical
      properties of tissues from OCE data, which is important for the further
      development of noninvasive elastography methods. 

PMID- 25860077
TI  - Nursing and midwife staffing needs in maternity wards in Burkina Faso referral
      hospitals.
AB  - BACKGROUND: In 2006, Burkina Faso set up a policy to subsidize the cost of
      obstetric and neonatal emergency care. This policy has undoubtedly increased
      attendance at all levels of the health pyramid. The aim of this study was to
      measure the capacity of referral hospitals' maternity services to cope with the
      demand for health services after the implementation of this policy. METHODS: This
      study was conducted in three referral health centres (CMAs, CHRs, and CHUs). The
      CHU Yalgado Ouedraogo (tertiary level) and the CMA in Sector 30 (primary level)
      were selected as health facilities in the capital, along with the Kaya CHR
      (secondary level). At each health facility, the study included official maternity
      ward staff only. We combined the two occupational categories (nurses and
      midwives) because they perform the same activities in these health facilities. We
      used the WISN method recommended by WHO to assess the availability of nurses and
      midwives. RESULTS: Nurses and midwives represented 38% of staff at the University
      Hospital, 65% in the CHR and 80% in the CMA. The number of nurses and midwives
      needed for carrying out the activities in the maternity ward in the University
      Hospital and the CMA is greater than the current workforce, with WISN ratio of
      0.68 and 0.79 respectively. In the CHR, the current workforce is greater than the
      number required (WISN ratio = 2). CONCLUSION: This study showed a shortage of
      nurses and midwives in two health facilities in Ouagadougou, which confirms that
      there is considerable demand. At the Kaya CHR, there is currently enough staff to
      handle the workload in the maternity ward, which may indicate a need to expand
      the analysis to other health facilities to determine whether a redistribution of
      health human resources is warranted.

PMID- 25860078
TI  - Role of triggering receptor expressed on myeloid cells-1/3 in Klebsiella-derived
      pneumosepsis.
AB  - Triggering receptor expressed on myeloid cells (TREM)-1 and -2 can affect Toll
      like receptor-mediated activation of immune cells. Klebsiella pneumoniae is a
      common cause of pneumonia-derived sepsis. Here we studied the role of TREM-1/3
      and TREM-2 in the host response during Klebsiella pneumonia. Macrophages lacking
      either TREM-1/3 or TREM-2 were tested for their responsiveness toward K.
      pneumoniae and for their capacity to internalize this pathogen in vitro. TREM-1/3
      and TREM-2-deficient mice were infected with K. pneumoniae via the airways, and
      their responses were compared with those in wild-type mice. TREM-1/3-deficient
      macrophages produced lower cytokine levels upon exposure to K. pneumoniae,
      whereas TREM-2-deficient macrophages released higher cytokine concentrations.
      TREM-2-deficient, but not TREM-1/3-deficient, macrophages showed a reduced
      capacity to phagocytose K. pneumoniae. TREM-1/3-deficient mice showed an impaired
      host defense during Klebsiella pneumonia, as reflected by worsened survival and
      increased bacterial growth and dissemination. In contrast, TREM-2 deficiency did
      not affect disease outcome. Although TREM-1/3 and TREM-2 influence macrophage
      responsiveness to K. pneumoniae in vitro, only TREM-1/3 contribute to the host
      response during Klebsiella pneumonia in vivo, serving a protective role. 

PMID- 25860079
TI  - Practical identification of human originated Lactobacillus species by amplified
      ribosomal DNA restriction analysis (ARDRA) for probiotic use.
AB  - Probiotics are gaining popularity and increasing the importance of their accurate
      speciation. Lactobacillus species are commonly used as probiotic strains mostly
      of clinical importance. Present knowledge indicates that at least 14
      Lactobacillus species are associated with the human intestinal tract. Currently,
      researchers are interested in developing efficient techniques for screening and
      selecting probiotics bacteria, but unfortunately most of these methods are time
      consuming, labor-intensive and costly. The aim of this study is to develop
      reliable, rapid and accurate method to identify 14 references Lactobacillus
      species that could have been found in the human alimentary tract by 16S ribosomal
      DNA restriction analysis. In this study, to develop an effective method for the
      genotype-based identification of the reference Lactobacillus species, 1.5 kb of
      16S rRNA nucleotide sequences of 14 Lactobacillus were collected from the Gene
      Bank aligned, in silico restricted and analyzed in respect to their 16S-rRNA
      restriction fragment polymorphism. In silico restriction profiles of 16S-rRNA
      indicated that FspBI, HinfI and DraI restriction enzymes (RE) are convenient for
      differentiation of 14 Lactobacillus species in human intestinal tract except Lb.
      casei and Lb. paracasei. The patterns of our experimental findings obtained from
      16S PCR-ARDRA completely confirmed our in silico patterns. The present work
      demonstrated that 16S PCR-ARDRA method with FspBI, HinfI and DraI RE is a rapid,
      accurate and reliable method for the identification of Lactobacillus species from
      human alimentary tract, especially during the identification of large numbers of
      isolates and any laboratory equipped with a thermo cycler for probiotic use. 

PMID- 25860080
TI  - Correction to differential stabilities and sequence-dependent base pair opening
      dynamics of watson-crick base pairs with 5-hydroxymethylcytosine, 5
      formylcytosine, or 5-carboxylcytosine.

PMID- 25860081
TI  - Solanioic Acid, an Antibacterial Degraded Steroid Produced in Culture by the
      Fungus Rhizoctonia solani Isolated from Tubers of the Medicinal Plant Cyperus
      rotundus.
AB  - Solanioic acid (1), a degraded and rearranged steroid that exhibits in vitro
      antibacterial activity against methicillin-resistant Staphylococcus aureus
      (MRSA), has been isolated from laboratory cultures of the fungus Rhizoctonia
      solani obtained from tubers of the plant Cyperus rotundus collected in Sri Lanka.
      The structure of solanioic acid (1) was elucidated by detailed analysis of NMR
      data, a single crystal X-ray diffraction analysis of a reduction product 2, and
      Mosher ester analysis on a derivative of the natural product. Solanioic acid (1)
      has an unprecedented carbon skeleton. 

PMID- 25860082
TI  - Child and adolescent cognitive behaviour therapy in South Africa: An editorial
      review.
AB  - The evidence base for cognitive behaviour therapy (CBT) (1) and other
      psychotherapeutic interventions in child and adolescent populations in low to
      middle income countries such as in South Africa is almost non-existent. In this
      review we explored the transportability of cognitive behaviour therapy
      interventions into the South African mental health care environment. Further
      investigations of CBT's effectiveness for children and adolescents and its
      cultural adaptability in South Africa are needed. (1)When using 'cognitive
      behaviour therapy' in this article we refer to all iterations and therapies that
      support the basic principles of CBT and that are evidenced based. 

PMID- 25860083
TI  - The development of parent-infant/child psychotherapy in South Africa: A review of
      the history from infancy towards maturity.
AB  - This paper takes the form of an account of the emergence of the field of
      psychoanalytically informed parent-infant/child psychotherapy in South Africa. It
      traces the origins and the development of the South African field by locating
      local practice within the international field. The influential links between
      international approaches and local practice and services are described. The
      historical account is based on a review of published parent-infant/child
      literature, including South African authored texts. Interviews with key local
      stakeholders and practitioners supplement the literature review. This paper
      endeavours to locate parent-infant/child psychotherapy more clearly on the map of
      mental health work in South Africa, and in so doing to promote the work as both a
      relevant and valuable intervention. 

PMID- 25860084
TI  - Predictors of non-condom use intentions by university students in Britain and
      Greece: The impact of attitudes, time perspective, relationship status, and
      habit.
AB  - OBJECTIVE: This study investigated the impact of socio-cognitive factors
      (attitudes and norms), time perspective (TP), relationship status (RS), and past
      sexual behaviour on intended non-condom use in 104 Greek and 93 British
      university undergraduates. METHOD: Data were obtained by a self-report
      questionnaire. Data analysis included correlation, regression and ANOVA
      procedures. RESULTS: Attitudes were the strongest predictors of non-condom use
      intentions for participants who had casual relationships or were single (i.e.
      unstable relationship context), and past behaviour was the strongest predictor of
      non-condom use intentions for those who perceived themselves to be in an
      exclusive relationship (i.e. stable relationship context). Past behaviour was the
      strongest predictorof intended non-condom use in relation to all the variables of
      this study. TP managed to predict non-condom use intentions and moderate the
      attitudes-intentions relationship. In terms of temporal influences, participants
      high in fatalistic TP were strongly inclined not to use condoms, irrespective of
      their attitudes, but TP did not differ as a function of culture. CONCLUSIONS: Our
      data revealed the value of considering the combined effects of relationship
      status, habit and attitudes, when investigating undergraduate non-condom use
      intentions and designing interventions. The construct of TP was introduced as a
      meaningful addition to sexual risk research.

PMID- 25860085
TI  - Working memory functioning in children with attention-deficit/hyperactivity
      disorder (ADHD): A comparison between subtypes and normal controls.
AB  - OBJECTIVE: Children with attention-deficit/hyperactivity disorder (ADHD) often
      experience working memory difficulties. However, research findings are
      inconsistent, making it difficult to compare results across studies. There are
      several reasons for this inconsistency. Firstly, most studies make no distinction
      between ADHD subtypes, despite evidence that predominantly inattentive ADHD
      (ADHD/I) represents a different neurocognitive profile to the hyperactive
      impulsive subtype (ADHD/HI). Secondly, documented studies use different tests of
      working memory which may be measuring different skills. Some assess only the
      verbal components of working memory and others the visuo-spatial; few of the
      tests assess both. Further, some tests employ a recognition methodology and
      others use recall, which require different brain regions and cognitive processes.
      To clarify these inconsistencies, the verbal and visuo-spatial working memory of
      children with ADHD/I, ADHD/HI and a control group with no ADHD symptoms were
      compared. METHOD: The Automated Working Memory Assessment and Ravens Coloured
      Progressive Matrices were administered to 72 children (ADHD/I n = 27; ADHD/HI n =
      25; control n = 20). RESULTS: The ADHD groups performed similarly, but were
      significantly poorer than the control group in all aspects of working memory.
      Storage abilities were stronger than processing abilities, while verbal and visuo
      spatial abilities were equally developed for all groups. CONCLUSION: ADHD-related
      deficits were apparent across working memory components, even when IQ was
      controlled for, suggesting a generalised impairment.

PMID- 25860086
TI  - Reliability of self report questionnaires for epidemiological investigations of
      adolescent mental health in Cape Town, South Africa.
AB  - OBJECTIVE: This study aimed to assess the reliability of a number of self report
      questionnaires for epidemiological investigations of adolescents' mental health
      in Cape Town, South Africa. The scales used were: the Short Mood and Feelings
      Questionnaire (SMFQ), Zung Self-rating Anxiety Scale (SAS), Self-esteem
      Questionnaire (SEQ), Harvard Trauma Questionnaire (HTQ) and Multi-Dimensional
      Scale of Perceived Social Support (MSPSS). METHOD: The self-report questionnaire
      (available in Afrikaans, English and isiXhosa) was administered to 237 grade 8
      students (14-15 years) on 2 occasions in metropolitan Cape Town high schools. The
      mean interval between first and second administration of the questionnaire was
      8.3 days. Test-retest reliability was assessed using Cohen's kappa and observed
      agreement. Pearson's correlation coefficients were used to assess consistency
      across total scores between occasion 1 and occasion 2. Cronbach's alpha was used
      to assess the internal consistency of each scale. RESULTS: All items had at least
      fair test-retest reliability (kappa > 0.20) apart from two items on the Self
      rating Anxiety Scale and one item on the Harvard Trauma questionnaire. Test
      retest reliability was strong for the HTQ (Pearson's correlation coefficient
      >0.75), moderate for the SAS, SEQ and MSPSS (0.50-0.74) and weak for the SMFQ
      (0.25-0.49). Cronbach's alpha for all scales was acceptable (>0.60). Analysis by
      the different language versions (Afrikaans/English and isi-Xhosa/ English) of the
      questionnaire indicated good internal consistency for most measures for all three
      languages. CONCLUSIONS: The results indicate that many of these instruments may
      be used reliably in South Africa to assess adolescent mental health and that the
      different language versions of the instruments used in the questionnaire are
      generally reliable for use in South African schools. However, some caution is
      required with the use of the SAS and SEQ in different language groups.

PMID- 25860087
TI  - Development and implementation of a peer-based mental health support programme
      for adolescents orphaned by HIV/AIDS in South Africa.
AB  - AIM: The article describes a framework and the process for the development of the
      peer-based mental health support programme and its implementation. The
      development of a peer-based mental health support programme is based on Erikson's
      theory on the adolescent phase of development, the psycho-educational processes;
      the peer approach and the orphaned adolescents lived experiences as conceptual
      framework. METHODS: A triangulation of five qualitative methods of photography,
      reflective diaries, focus groups, event history calendar and field notes were
      used to capture the lived experiences of adolescents orphaned to HIV and AIDS.
      Analysis of data followed Colaizzi's method of data analysis. RESULTS: The
      combination of psycho-education, Erikson's stages of development and peer support
      assisted the participants to gain knowledge and skills to overcome adversity and
      to assist them to become to more resilient. CONCLUSION: The peer based mental
      health support programme if used would enhance the mental health of adolescent
      orphans.

PMID- 25860088
TI  - A profile of students receiving counselling services at a university in post
      apartheid South Africa.
AB  - OBJECTIVES: The purpose of this study was to describe a profile of students
      seeking counselling at a racially diverse university in post-apartheid South
      Africa as a means to demonstrate the importance of routinely collecting and
      analysing student counselling data at university-based centres across the
      country. METHODS: Student data were extracted from the only two counselling
      centres based at the University of the Witwatersrand in Johannesburg that
      provided services to 831 students during 2008. The 26 243 students that did not
      seek counselling during this period formed the comparison group. These data were
      analysed using logistic regression. RESULTS: Black, female and students within
      the 21-25 year age category were more likely to receive counselling, and
      presenting problems varied by population group. CONCLUSIONS: Given the country's
      past and continued levels of social asymmetry, we argue that the development of
      standardised university-based reporting systems able to describe the
      characteristics and presenting problems of students seeking counselling across
      South African universities should be prioritised by its higher education sector.
      Timely access to information of this kind is crucial to the generation of
      evidence-based mental health interventions in a population that is especially
      important to the country's development vision.

PMID- 25860090
TI  - Engaging boys in treatment: Creative approaches to the therapy process.

PMID- 25860089
TI  - Risk factors for premature termination of treatment at a child and family mental
      health clinic.
AB  - OBJECTIVE: Premature termination of treatment amongst children and families
      attending mental health services is a significant problem for both outcomes
      research and clinical practice in South Africa and elsewhere. This study
      investigated factors that are associated with premature termination of treatment
      at a public service child and family clinic in Cape Town. METHOD: A retrospective
      archival analysis of clinic files from 2002-2009 was conducted. Administrative,
      child and family factors, and type of treatment were explored as risk factors for
      premature termination. RESULTS: A single-parent household and the presence of a
      child or oppositional defiant disorder were risk factors for premature
      termination of treatment, while the presence of a maternal psychiatric diagnosis
      was associated with a lower likelihood of terminating treatment prematurely.
      Conducting a scholastic assessment with the child was associated with a lower
      risk of premature termination, while there was a trend towards a higher risk of
      premature termination when individual child therapy was the recommended
      treatment. CONCLUSIONS: This study offers recommendations for how these findings
      could assist South African clinicians to enhance client retention in child and
      family mental health services, and suggestions for future research.

PMID- 25860091
TI  - Journal abstracts from current research in the field of child and adolescent
      mental health.

PMID- 25860092
TI  - A Combined Experimental and Theoretical Study of the Reaction OH + 2-Butene in
      the 400-800 K Temperature Range.
AB  - We report a combined experimental and theoretical study of the OH + cis-2-butene
      and OH + trans-2-butene reactions at combustion-relevant conditions: pressures of
      1-20 bar and temperatures of 400-800 K. We probe the OH radical time histories by
      laser-induced fluorescence and analyze these experimental measurements with aid
      from time-dependent master-equation calculations. Importantly, our investigation
      covers a temperature range where experimental data on OH + alkene chemistry in
      general are lacking, and interpretation of such data is challenging due to the
      complexity of the competing reaction pathways. Guided by theory, we unravel this
      complex behavior and determine the temperature- and pressure-dependent rate
      coefficients for the three most important OH + 2-butene reaction channels at our
      conditions: H abstraction, OH addition to the double bond, and back-dissociation
      of the OH-butene adduct. 

PMID- 25860093
TI  - Youths navigating social networks and social support systems in settings of
      chronic crisis: the case of youth-headed households in Rwanda.
AB  - Youth-headed households in Rwanda live in a context of chronic crisis, where
      poverty, disease and uncertainty are not exceptional but characterise people's
      daily lived reality. Struggling under the pressures of economic deprivation,
      social isolation, abuse and exploitation, these youths experience social
      suffering and feel the impact of social forces on their everyday lives. Yet, amid
      constraints in the environment, youths demonstrate resilience by actively
      navigating their social networks and working to create opportunities for the
      future. The article describes qualitative research carried out in three
      communities in Rwanda, between 2006 and 2010, examining the support systems of
      Rwandan youths affected by the HIV epidemic and socio-political conflict and
      exploring how youth heads of households navigate social networks in order to
      buffer the suffering in their lives. It is argued that social support is vital
      for these youths as they struggle to survive, seek to gain a degree of control
      over their lives, and strive to have a hopeful future. Examples show the
      remarkable ability of such youths to confront adversity by mobilising resources
      and exhibiting agency, although they may continue to experience suffering when
      support is lacking. The article concludes that to improve wellbeing and reduce
      suffering for youth-headed households, it is critical to recognise the social
      relations that may limit or enhance these youths' ability to navigate their
      social environment. Youths' agency needs to be recognised as a means to reduce
      the detrimental impacts of their actions and instead build on positive
      strategies, enabling them as they navigate their life course towards future
      possibilities. Finally, the dual role of youth heads of households - as
      individuals in adult roles and as youths - should be recognised, with initiatives
      to build them up designed around economic strengthening and mentorship. 

PMID- 25860094
TI  - Safeguarding inheritance and enhancing the resilience of orphaned young people
      living in child- and youth-headed households in Tanzania and Uganda.
AB  - This article explores the resilience of orphaned young people in safeguarding
      physical assets (land and property) inherited from their parents and sustaining
      their households without a co-resident adult relative. Drawing on the concept of
      resilience and the sustainable livelihoods framework, the article analyses the
      findings of an exploratory study conducted in 2008-2009 in Tanzania and Uganda
      with 15 orphaned young people heading households, 18 of their siblings, and 39
      NGO workers and community members. The findings suggest that inherited land and
      property were key determining factors in the formation and viability of the child
      and youth-headed households in both rural and urban areas. Despite experiences
      of stigma and marginalisation in the community, social networks were crucial in
      enabling the young people to protect themselves and their property, providing
      access to material and emotional resources, and enhancing their skills and
      capabilities to develop sustainable livelihoods. Support for child- and youth
      headed households needs to recognise young people's agency and should adopt a
      holistic approach to their lives by analysing the physical assets, material
      resources, and human and social capital available to the household, as well as
      giving consideration to individual young people's wellbeing, outlook and
      aspirations. Alongside cash transfers and material support, youth-led collective
      mobilisation that is sustained over time may also help build resilience and
      foster supportive social environments in order to challenge property-grabbing and
      the stigmatisation of child- and youth-headed households. 

PMID- 25860095
TI  - Challenges and coping strategies of orphaned children in Tanzania who are not
      adequately cared for by adults.
AB  - Orphaned children in poor rural communities sometimes have no adult who is able
      to care for them or else the adult caregiver is not able to provide adequate
      care. Tanzania remains one of the poorest countries in the world, and poverty
      frequently constrains foster care. Although HIV prevalence is declining, AIDS is
      still a major cause of orphaning. This article explores the challenges and coping
      strategies accompanying two possible life trajectories for orphaned children
      without adequate adult care: 1) that they remain in rural areas in child-headed
      households, or 2) that they are trafficked to an urban area. Antonovsky's
      salutogenic model is used as the theoretical framework. The data come from two
      separate phenomenological studies with vulnerable children. In the first study,
      in-depth interviews were held with 12 orphaned children in a poor rural area;
      data concerning three child heads of households are included here. In the second
      study, 15 girls who were trafficked from rural areas to Dar es Salaam gave
      extended life-history narrations; data are included for nine of the girls who
      were orphaned. Loss of parents, a lack of cash, and the need to balance school
      attendance with food production were chronic stressors for the children heading
      households, while resources included income-generation strategies and the ability
      to negotiate with teachers for time to cultivate. For the trafficked girls
      chronic stressors included exploitation, long working hours, little or no pay,
      isolation and rape. Resources for them, although limited, included faith networks
      and neighbours; escape from the exploitative situation frequently involved
      external help. We conclude that given physical and social assets the child-headed
      households were able to cope with the challenges of caring for themselves and a
      younger child, but isolation and dependency on employers made it difficult for
      the trafficked girls to cope with this exploitation. The salutogenic model proved
      a useful tool in analysing the coping strategies of children living without
      adequate adult care. 

PMID- 25860096
TI  - Children's caregiving of HIV-infected parents accessing treatment in western
      Kenya: challenges and coping strategies.
AB  - This article describes qualitative research carried out in rural western Kenya in
      a setting characterised by poverty and high HIV prevalence. It discusses the
      responsibilities and challenges that children face when becoming the primary
      caregiver to an HIV-infected parent enrolled in an antiretroviral therapy (ART)
      programme, and the coping strategies these children adopt to deal with hardship.
      The research draws attention to the difficulties and opportunities of
      strengthening home-based care services to facilitate better conditions for
      children to cope as caregivers. Ethnographic data was collected through a variety
      of qualitative research methods (in-depth interviews, focus group discussions,
      drama, diaries and participant observation) during five months of fieldwork in
      2009. Informants included caregiving children (ages 6-16 years), HIV-infected
      parents, community members, school teachers, community health workers, NGO
      representatives, and other home-based-care stakeholders. The findings reveal that
      children may play a significant role in the daily healthcare of an HIV-infected
      parent enrolled in an ART programme. The main responsibilities of the children
      caring for parents on ART were intimate care and nursing, household duties, and
      income-generating activities. A number of social factors determine children's
      ability to cope with these responsibilities, including the caregiving children's
      access to nutritious food, social and emotional support, assistance from
      community health workers, and adequate healthcare knowledge. The level and
      consequences of the children's caregiving activities as well as their ability to
      cope were heavily influenced by: 1) the dynamics of their parent's health
      condition while on antiretroviral (ARV) medication, and 2) the context in which
      the child sought social and economic resources. There is an urgent need for home
      based care services to look holistically at people's needs and resources at the
      household level, and, in particular, to consider the hardships and coping
      strategies of children who live with a parent on ART. 

PMID- 25860097
TI  - The use of rites of passage in strengthening the psychosocial wellbeing of
      orphaned children in Botswana.
AB  - Children who have been bereaved in the context of AIDS may experience many
      challenges to their psychosocial wellbeing. Programmes to help orphaned children
      are usually anchored in child rights. As the individual focus of rights-based
      approaches is inept in African collectivist culture, NGOs tend to make use of
      group approaches in psychosocial support programmes. One orphan-strengthening
      programme in Botswana, called the Ark for Children, uses rites of passage and
      rites of affirmation as part of a therapeutic retreat. This study explored how
      rites of passage and rites of affirmation contribute to psychosocial
      strengthening of orphaned children in Botswana. Ten orphaned children were
      involved in five rounds of data collection during a 16-day therapeutic retreat;
      and eight social workers answered questions on the effectiveness of the therapy.
      A supplementary document analysis was also completed, which included retreat
      reports since 2001 and correspondence from community-based support workers and
      graduates of the programme. Participants reported that the rites used during the
      retreat helped them to commit to therapeutic transformation. During a retreat,
      all the participants witness and support each individual going through each rite 
      a process reported to foster and strengthen group formation. It was documented
      that the symbols used as part of the themed rites of affirmation are used by
      participants for years afterwards as reminders of their transformation and
      commitment to the group. We conclude that rites of passage can provide a powerful
      tool to help children commit to therapeutic transformation, build the supportive
      group, and enable the community to recognise and affirm that the children return
      as changed individuals and members of the group. 

PMID- 25860098
TI  - 'Read me to resilience': Exploring the use of cultural stories to boost the
      positive adjustment of children orphaned by AIDS.
AB  - The study explored whether and how culturally sensitive stories can encourage
      resilience in young children orphaned by AIDS. The purpose of the investigation
      was allied to the paradigm of positive psychology, which focuses on the promotion
      of potential strengths to buffer children against adversity, as well as on social
      ecological understandings of resilience, which emphasise that social ecologies
      have a duty to facilitate children's positive adjustment to adversity. A pre-post
      intervention evaluation was used to gather qualitative data on orphaned
      children's resilience to AIDS-related adversity by employing participatory visual
      methods. The intervention, called Read-me-to-Resilience (Rm2R), consisted of
      telling 22 culturally sensitive stories to the children. We compared the pre- and
      post-intervention data for each participant before thematically analysing the
      total findings. Our analysis indicates that the children's resilience had been
      bolstered in the period between the pre-test and post-test. We conclude that
      culturally relevant stories could be used by South African caregivers, service
      providers, and educators as an accessible, inexpensive and ready-made tool to
      directly empower children who have been orphaned by AIDS. 

PMID- 25860099
TI  - Schoolchildren affected by HIV in rural South Africa: schools as environments
      that enable or limit coping.
AB  - The importance of psychosocial support for the wellbeing of children made
      vulnerable by HIV is a frequently discussed topic in the fields of education and
      HIV-related social science research. For children to juggle both the demands of
      education and the impacts of HIV is an enormous challenge. Against this
      background, schools have been hailed as potential sources of support, yet we know
      little about how the school environment can provide support, which might reflect
      the lack of input from schoolchildren themselves. This article explores how
      schoolchildren made vulnerable due to HIV and AIDS might cope and even thrive in
      a rural school environment in South Africa. I argue that schoolchildren's own
      contributions and abilities are fundamental to accelerate their coping
      strategies, allowing them to step back from vulnerability and so gain perspective
      about it. An inductive analysis makes use of data generated from a method of
      participatory photography (PhotoVoice), conducted with schoolchildren aged 16-18
      years at a rural school in KwaZulu-Natal Province. The article draws on the
      concept of appreciative inquiry as a framework for examining coping strategies
      among schoolchildren made vulnerable by HIV. The findings point to the
      schoolchildren's ability to identify and access resources that will encourage
      them to cope with HIV-related adversities in their own lives. The participants
      revealed an ability to point out perceived social and structural challenges that
      have a dominant influence on their coping strategies. 

PMID- 25860100
TI  - How disclosure and antiretroviral therapy help HIV-infected adolescents in sub
      Saharan Africa cope with stigma.
AB  - HIV-related stigma has a major impact on the health and psychosocial wellbeing of
      HIV-infected children and youths. While there is some debate about the extent to
      which improved access to antiretroviral therapy (ART) contributes to a reduction
      in HIV stigma, we know little about how adolescents who know their HIV status and
      who are enrolled in ART experience and cope with stigma. The aim of the research
      was to understand and identify the pathways between HIV-status disclosure, ART,
      and children's psychosocial wellbeing, including from the perspective of
      adolescents themselves. Two qualitative studies were carried out, in Botswana and
      Tanzania, in 2011: 16 adolescents and three healthcare workers were enrolled in
      Botswana, and 12 adolescents and two healthcare workers were enrolled in
      Tanzania. The data were collected through individual and group interviews as well
      as participant observation. The recorded interviews were transcribed and analysed
      using thematic network analysis. The findings indicate that HIV-status disclosure
      enabled adolescents to engage effectively with their ART treatment and support
      groups, which in turn provided them with a sense of confidence and control over
      their lives. Although the adolescents in the two studies were still experiencing
      stigma from peers and community members, most did not internalise these
      experiences in a negative way, but retained hope for the future and felt pity for
      those untested and uninformed of their own HIV status. We conclude that
      disclosure and good HIV-related services provide an important platform for HIV
      infected adolescents to resist and cope with HIV stigma. 

PMID- 25860101
TI  - Strategies to bring about change: a longitudinal study on challenges and coping
      strategies of orphans and vulnerable children and adolescents in Namibia.
AB  - Longitudinal research provides insight about the life trajectories of children,
      the challenges that children experience in different phases of their lives, and
      the way children cope with these challenges. The article examines the
      perspectives of 14 orphaned or vulnerable children, initially aged 9 to 12 years
      (in grades 3 and 4), concerning changes in their difficulties and coping
      strategies. The children participated in the research in 2003 and again in a
      follow-up study in 2010 to 2012. Focus group discussions with the
      children/adolescents were used, as well as child-orientated methods such as
      drawings, and in-depth interviews with the adolescents and caregivers. Most of
      the participants described their life situation as better at the time of the
      2010/12 study than it had been in 2003. In general, they were receiving more
      financial support than before from their immediate and extended family or were
      supporting themselves. One important change since 2003 was that nine of the 14
      had since received a state-provided child welfare grant for at least some years.
      Also, those who said they had previously experienced mistreatment had since left
      these home situations. The children's agency in making positive changes to their
      life situations is described by the participants. As adolescents, they tried to
      access family support by actively asking for financial assistance, and in return
      they generally felt obligated to support the family once they began earning an
      income. The strategies they most used to get away from abusive home situations
      were to inform a relative about the mistreatment or to run away. Children's and
      adolescents' limitations concerning strategies for improving their adverse living
      situations are also discussed. 

PMID- 25860102
TI  - Questioning the use-value of social relationships: care and support of youths
      affected by HIV in child-headed households in Port Elizabeth, South Africa.
AB  - The opinion that the extended family can fulfil its supportive role in assisting
      child-headed households continues to exist. How these households encounter
      support, what this support entails, and how they experience this support is an
      under-researched subject. Most research literature on this topic emphasises child
      headed households' material and financial support. However, although financial
      support is vital, emotional support to cope with the loss of loved ones, or with
      loneliness and insecurity, is also much needed, as well as adult assistance in
      obtaining formal support, such as social welfare grants. Thus, to what extent are
      child-headed households capable of capitalising on existing (extended) family and
      community members' care and support? This article addresses this question by
      exploring the 'use-value' of social relationships among child-headed households
      in Port Elizabeth, South Africa. The coping strategies of the child-headed
      households are discussed and analysed, indicating the children's interpretations
      and valuation of social relationships and support, whether this increased their
      potential access to other resources, and whether this support could be considered
      sufficient. Despite some exceptions, we argue that support from relatives or
      neighbours is often ambiguous and of little use-value from the viewpoint of a
      child-headed household. Insights from these findings might be of interest to
      those involved in support programmes for these households, including the
      assignment of an adult mentor - which is based on the assumption that existing
      networks of extended family and community members will help orphaned and
      vulnerable children to cope. 

PMID- 25860103
TI  - Active pneumatic control of centrifugal microfluidic flows for lab-on-a-chip
      applications.
AB  - This paper reports a novel method of controlling liquid motion on a centrifugal
      microfluidic platform based on the integration of a regulated pressure pump and a
      programmable electromechanical valving system. We demonstrate accurate control
      over the displacement of liquids within the system by pressurizing simultaneously
      multiple ports of the microfluidic device while the platform is rotating at high
      speed. Compared to classical centrifugal microfluidic platforms where liquids are
      solely driven by centrifugal and capillary forces, the method presented herein
      adds a new degree of freedom for fluidic manipulation, which represents a
      paradigm change in centrifugal microfluidics. We first demonstrate how various
      core microfluidic functions such as valving, switching, and reverse pumping
      (i.e., against the centrifugal field) can be easily achieved by programming the
      pressures applied at dedicated access ports of the microfluidic device. We then
      show, for the first time, that the combination of centrifugal force and active
      pneumatic pumping offers the possibility of mixing fluids rapidly (~0.1 s) and
      efficiently based on the creation of air bubbles at the bottom of a microfluidic
      reservoir. Finally, the suitability of the developed platform for performing
      complex bioanalytical assays in an automated fashion is demonstrated in a DNA
      harvesting experiment where recovery rates of about 70% were systematically
      achieved. The proposed concept offers the interesting prospect to decouple basic
      microfluidic functions from specific material properties, channel dimensions and
      fabrication tolerances, surface treatments, or on-chip active components, thus
      promoting integration of complex assays on simple and low-cost microfluidic
      cartridges. 

PMID- 25860106
TI  - Pregnancy Risk Assessment Monitoring System and the W.K. Kellogg Foundation joint
      project to enhance maternal and child health surveillance: focus on
      collaboration.
AB  - Maternal and child health (MCH) surveillance data are important for understanding
      gaps in services and disparities in burden of disease, access to care, risk
      behaviors, and health outcomes. However, national and state surveillance systems
      are not always designed to gather sufficient data for calculating reliable
      estimates of the health conditions among high-risk or underrepresented population
      subgroups living in smaller geographic areas. The Centers for Disease Control and
      Prevention's Pregnancy Risk Assessment Monitoring System (PRAMS) has conducted
      surveillance for over 25 years in collaboration with state and city health
      departments. In 2012, PRAMS embarked on a multiyear collaboration with the W.K.
      Kellogg Foundation (WKKF) to include oversampling of minority and low-income
      women in selected geographic areas in four states (Louisiana, Michigan,
      Mississippi, and New Mexico) where the WKKF funded extensive place-based
      initiatives are located. The PRAMS-WKKF collaboration has broad implications for
      promoting meaningful collaboration between public, private, local, state, and
      federal organizations to address MCH data gaps on disparities, and for improving
      the availability of information needed for MCH programs, policy makers, and
      women. 

PMID- 25860107
TI  - A pooled analysis of the efficacy of desvenlafaxine for the treatment of major
      depressive disorder in perimenopausal and postmenopausal women.
AB  - BACKGROUND: Few studies in the literature have examined the efficacy of
      antidepressant drugs in perimenopausal and postmenopausal women. The objective of
      the current study was to assess the efficacy of desvenlafaxine (administered as
      desvenlafaxine succinate) separately in perimenopausal and postmenopausal women
      with major depressive disorder (MDD). METHODS: Data were pooled from two double
      blind, placebo-controlled clinical trials enrolling perimenopausal and
      postmenopausal women (40-70 years old) diagnosed with MDD. Patients were randomly
      assigned to receive desvenlafaxine 100 to 200 mg/day or placebo (8 weeks) or
      desvenlafaxine 50 mg/day or placebo (10 weeks). The primary efficacy end point
      for each trial was change from baseline in Hamilton Rating Scale for Depression
      (HAM-D17) total score at week 8. Secondary end points included change from
      baseline in Sheehan Disability Scale (SDS) and Menopause Rating Scale (MRS)
      scores. Changes from baseline in continuous variables were analyzed using
      analysis of covariance with treatment, region, and baseline in the model. All
      treatment comparisons were carried out separately in perimenopausal or
      postmenopausal women, in individual studies, and in the pooled population,
      adjusting for menopausal status and study. RESULTS: A total of 798 patients were
      included in the full analysis set (perimenopausal, n=252; postmenopausal, n=546).
      Desvenlafaxine significantly reduced HAM-D17 total scores versus placebo at week
      8 in both perimenopausal (-10.3 vs. -6.5; p<0.001) and postmenopausal women (
      10.1 vs. -7.6; p<0.001). Significant improvements in SDS and MRS total scores
      were also observed for desvenlafaxine versus placebo in perimenopausal (p <=
      0.024) and postmenopausal women (p <= 0.009). A significant treatment by
      menopausal status interaction was observed for SDS only (p=0.036). CONCLUSIONS:
      Desvenlafaxine demonstrated antidepressant efficacy in both perimenopausal and
      postmenopausal subgroups of women with MDD. DISCLAIMER: In September 2011, Pfizer
      received a Complete Response Letter from the United States Food and Drug
      Administration on its application for approval to market desvenlafaxine for the
      treatment of moderate to severe vasomotor symptoms associated with menopause. The
      Complete Response Letter states that the data included in the application are not
      sufficient to establish an acceptable risk/benefit profile for the treatment of
      vasomotor symptoms in the general population of postmenopausal women, and
      therefore desvenlafaxine is not approved for the treatment of vasomotor symptoms
      in the United States at this time. This decision does not impact desvenlafaxine's
      approval for the treatment of MDD in adults.

PMID- 25860108
TI  - Enhancing referral of sexually active adolescent females from the emergency
      department to family planning.
AB  - BACKGROUND: Female adolescents at high pregnancy risk frequently visit the
      emergency department (ED) and lack primary providers. It is unclear if current
      methods of ED referral are successful. The objective of this pilot study was to
      assess the potential effect and feasibility of a standardized, enhanced method of
      referral of sexually active females from an ED for family planning (FP). METHODS:
      We conducted an ED-based intervention study using an enhanced referral process,
      which included a wallet card advertising a walk-in, adolescent-friendly FP clinic
      and a standardized ED physician monologue. ED physicians were instructed to
      disseminate the enhanced process to sexually active females ages 12-19 years
      (intervention group). Patients receiving the intervention were prospectively
      enrolled. The control group consisted of patients who, on retrospective review,
      came to the ED during the enrollment period and were eligible but were not
      enrolled. We used the electronic medical record (EMR) to identify and randomly
      select missed eligible patients (control group) and accumulated one control for
      each case. The primary outcome was FP follow-up within 2 months, measured by EMR
      review. RESULTS: The intervention (n=101) and control groups (n=101) were similar
      in age, prior ED visits (54% versus 56%), and previous FP visits (28% versus
      28%). The absolute difference in follow-up to a FP clinic between the enhanced
      referral group (7%; 7/101) compared with the nonenhanced referral group (5%;
      5/101) was only 2% (95% confidence interval -5% to 9%). Feasibility of the
      intervention was modest, with a best-case scenario of 59/160 (37%) of eligible
      patients captured. CONCLUSIONS: An enhanced referral initiative relying on
      physician participation did not substantially increase follow-up rates to a FP
      clinic and showed modest feasibility. More research is required to identify
      effective means of ED-based referral for preventive reproductive care.

PMID- 25860109
TI  - An integrated network of microRNA and gene expression in ovarian cancer.
AB  - BACKGROUND: Ovarian cancer is a deadly female reproductive cancer. Understanding
      the biological mechanisms underlying ovarian cancer could help lead to quicker
      and more accurate diagnosis and more effective treatments. Both changes in
      microRNA(miRNA) expression and miRNA/mRNA dysregulation have been associated with
      ovarian cancer. With the availability of whole-genome miRNA and mRNA sequencing
      we now have new potentials to study these associations. In this study, we
      performed a comprehensive analysis of miRNA and mRNA expression in ovarian cancer
      using an integrative network approach combined with association analysis.
      RESULTS: We developed an integrative approach to construct a network that
      illustrates the complex interplay among miRNA and gene expression from a systems
      perspective. Our method is composed of expanding networks from eQTL associations,
      building network associations in eQTL analysis, and then combine the networks
      into an integrated network. This integrated network takes account of miRNA
      expression quantitative trait loci (eQTL) associations, miRNAs and their targets,
      protein-protein interactions, co-expressions among miRNAs and genes respectively.
      Applied to the ovarian cancer data set from The Cancer Genome Atlas (TCGA), we
      created an integrated network with 167 nodes containing 108 miRNA-target
      interactions and 145 from protein-protein interactions, starting from 44 initial
      eQTLs. This integrated network encompassed 26 genes and 14 miRNAs associated with
      cancer. In particular, 11 genes and 12 miRNAs in the integrated network are
      associated with ovarian cancer. CONCLUSION: We demonstrated an integrated network
      approach that integrates multiple data sources at a systems level. We applied
      this approach to the TCGA ovarian cancer dataset, and constructed a network that
      provided a more inclusive view of miRNA and gene expression in ovarian cancer.
      This network included four separate types of interactions among miRNAs and genes.
      Simply analyzing each interaction component in isolation, such as the eQTL
      associations, the miRNA-target interactions or the protein-protein interactions,
      would create a much more limited network than the integrated one.

PMID- 25860110
TI  - Quantum chemical study of the isomerization of 24-methylenecycloartanol, a
      potential marker of olive oil refining.
AB  - Quantum chemical calculations on the isomerization of 24-methylenecycloartanol
      are described. An energetically viable mechanism, with a rate-determining
      protonation step, is proposed. This rearrangement may find applicability in tests
      for determining if an olive oil has been refined. 

PMID- 25860111
TI  - Curcumin and hydroxamate-derivative (PCI-34058) interfere with histone
      deacetylase I catalytic core Asp-His charge relay system: atomistic simulation
      studies.
AB  - Histone deacetylases (HDACs) are representative targets for the natural and
      synthetic chemicals used to transform cells to confer antitumor properties. In
      the current study, curcumin and hydroxamate-derivative PCI-34058-bound HDAC1 were
      subjected to atomistic simulation. The results support the view that fitting of
      curcumin and PCI-34058 within the HDAC1 pocket depends on extensive interactions
      between the aromatic moieties of the inhibitors and the extensive network of
      aromatic amino acid side chains lining the pocket of HDAC1. The interaction
      forces a local perturbation of the coiled structures connecting the pocket
      residues resulting in ligand-induced tightening of the pocket. In addition to the
      competitive occupancy of the histone-acetyl-lysine binding pocket by the
      inhibitors, interference with the in-pocket aspartate-histidine (ASP-HIS) charge
      relay system was also observed in inhibitor-bound HDAC1 systems. In conclusion,
      curcumin and PCI-34058-mediated ligand-dependent HDAC1 tunnel closure interferes
      negatively with the ASP-HIS charge relay system in HDAC1. Future design of HDAC
      inhibitors may benefit from optimizing competitive interaction with the ligand
      site and interference with the charge relay system. 

PMID- 25860113
TI  - [Chronic myelogenous leukemia].
AB  - The advent of tyrosine kinase inhibitors (TKI) has improved the prognosis and
      outcome of patients with chronic myelogenous leukemia (CML) considerably.
      Compared with imatinib, the first-line use of second-generation inhibitors
      nilotinib and dasatinib has led to faster and deeper molecular remissions
      accompanied by a differential adverse effect profile. An essential part of the
      management of CML patients is the guideline-based application of cytogenetics and
      standardized polymerase chain reaction techniques to regularly assess the
      remission status. Long-lasting treatment-free remission in a minority of patients
      led to hopes for the curability of CML in a significant minority of patients. The
      use of interferon alpha combined with or after TKI therapy is associated with the
      induction of an immune response toward the leukemic clone. This innovative
      treatment approach is currently under prospective investigation to improve long
      term response. The coordinated cooperation of academic and regional hospitals,
      office-based hematologists, laboratories, and patient representatives allows for
      up-to-date patient care and the early use of new therapeutic options in patients
      at risk. 

PMID- 25860114
TI  - Mammographic density in relation to tumor biomarkers, molecular subtypes, and
      mode of detection in breast cancer.
AB  - PURPOSE: Mammographic density is an established risk factor for breast cancer;
      however, the relation to tumor pathological parameters including the androgen
      receptor and molecular subtypes has not been extensively studied. METHODS: In the
      Malmo Diet and Cancer Study, 733 invasive breast cancers were diagnosed from 1991
      to 2007. Mammographic density was defined qualitatively. Tumor biomarker
      information including estrogen receptor (ER), progesterone receptor, androgen
      receptor (AR), human epidermal growth factor 2 (HER2), and Ki67 was collected.
      Surrogate molecular subtypes were defined as luminal A, luminal B, HER2 positive
      and triple-negative breast cancer (TNBC). RESULTS: Among the 632 tumors with
      mammographic and pathological information, 352 tumors were screening-detected and
      280 clinically detected. Higher mammographic density was associated with ER
      negative tumors [ORadj 1.93 (1.04-3.59)] and TNBC [ORadj 2.44 (1.01-5.89),
      luminal A reference], in clinically detected breast cancer. Similarly, higher
      mammographic density was associated with AR-negative tumors [ORadj 1.77 (0.80
      3.93)] in clinically detected breast cancer, though the evidence for this
      association was weak. CONCLUSIONS: In clinically detected breast cancer, but not
      in screening-detected, higher mammographic density was associated with ER
      negative tumors including TNBC. This study highlights the need for taking mode of
      detection into consideration when addressing mammographic density and tumor
      biomarkers.

PMID- 25860115
TI  - Preeclampsia and subsequent breast cancer risk.

PMID- 25860116
TI  - Comparative transcriptome analysis of the petal degeneration mutant pdm in
      Chinese cabbage (Brassica campestris ssp. pekinensis) using RNA-Seq.
AB  - Flowering, which plays a crucial role in the growth and development of flowering
      plants, is a crucial point from vegetative growth to reproductive growth. The
      goal of this study was to examine the differences between the transcriptomes of
      the Chinese cabbage mutant pdm and the corresponding wild-type line 'FT'. We
      performed transcriptome analysis on mRNA isolated from flower buds of pdm and
      'FT' using Illumina RNA sequencing (RNA-Seq) data. A total of 117 differentially
      expressed genes (DEGs) were detected. Among the DEGs, we identified a number of
      genes involved in floral development and flowering, including an F-box protein
      gene, EARLY FLOWERING 4 (ELF4), and transcription factors BIGPETAL (BPE) and
      MYB21 (v-myb avian myeloblastosis viral oncogene homolog); differential
      expression of these genes could potentially explain the difference in the flowers
      between pdm and 'FT'. In addition, the expression patterns of 20 DEGs, including
      12 floral development and flowering-related genes and eight randomly selected
      genes, were validated by qRT-PCR, and the results were highly concordant with the
      RNA-Seq results. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes
      pathway enrichment analyses were performed to better understand the functions of
      these DEGs. We also identified a large number of single nucleotide polymorphism
      and insertion/deletion markers, which will be a rich resource for future marker
      development and breeding research in Chinese cabbage. Also, our analysis revealed
      numerous novel transcripts and alternative splicing events. The transcriptome
      analysis provides valuable information for furthering our understanding of the
      molecular mechanisms that regulate the flowering process, and establishes a solid
      foundation for future genetic and functional genomic studies in Chinese cabbage. 

PMID- 25860117
TI  - Long-lived luminescent soft materials of hexanitratosamarate(III) complexes with
      orange visible emission.
AB  - Sm(III)-based ionic liquids incorporating hexanitratosamarate(III) anions were
      obtained and fully characterized as novel Sm(III)-containing organic complexes.
      The structure of the ionic liquids was determined by single-crystal X-ray
      diffraction (1: monoclinic system C2/c space group with cell parameters: a =
      19.5624(4) A, b = 10.11895(18) A, c = 33.2256(6) A, beta = 101.2912(18) degrees ,
      Z = 8). The central Sm(III) ion is 12-coordinated by six bidentate nitrate
      ligands with twelve oxygen donors to form a [Sm(NO3)6](3-) anion. The low melting
      point, high thermostability and wide liquid range of these ionic liquids were
      determined in detail. All the complexes 1-5 display orange luminescence, rather
      than red luminescence as in most Sm(III)-containing organic complexes. Three
      characteristic monochromatic bands and an intense emission, derived from (4)G5/2
      >(6)HJ (J = 5/2, 7/2, and 9/2) intraconfigurational f-f transitions, were
      revealed. All these complexes exhibit long luminescence lifetimes.

PMID- 25860118
TI  - [Ipsilateral THA after stemmed TKA: Risk of interprosthetic fracture?].
AB  - BACKGROUND: There is an increasing number of patients who have undergone stemmed
      total knee arthroplasty and total hip arthroplasty in the same leg. These
      patients may be at increased risk of periprosthetic and interprostethic fracture.
      Etiology and the potential therapy strategies are not well represented in the
      current literature. OBJECTIVES: Determination of the risk factors for
      interprosthetic fractures and possible prevention. MATERIALS AND METHODS: We
      performed a review of the literature and additionally a survey among experts
      (members of the German Association for Arthroplasty [AE]) to investigate the risk
      and the necessity for a preventive internal fixation. RESULTS: There are only a
      few biomechanical studies. The interprosthetic distance seems to have little
      influence on the fracture risk, but the thickness of the cortex and the cortical
      area at the diaphysis seems to be important. The value of a bridging
      osteosynthesis remains uncertain. Ninety experts took part in the survey. The
      risk of fracture risk was estimated to be only slight to medium. Opinions
      regarding the necessity of preventive internal fixation were heterogeneous.
      CONCLUSIONS: The indication for preventive internal fixation could be derived
      neither from the literature nor from the survey of experts. The thickness of the
      cortex and co-morbidities (osteoporosis, tendency to fall, and medication) seem
      to be more important than the interprosthetic distance.

PMID- 25860119
TI  - [Individualized total knee arthroplasty].
AB  - This article describes the rationale and the surgical technique of patient
      specific uni-, bi-, or three-compartmental knee arthroplasty using the second
      generation (G2) of ConforMISTM technology. The patient-individual implants and
      instruments are designed and fabricated based on data from a preoperative
      computed tomography of the lower limb. The disposable patient-specific drill
      guides and cutting-jigs are manufactured under consideration of the anatomical
      and biomechanical axes of the knee joint and mediate efficient pre-navigation of
      the saw-cuts on the femoral and tibial bone without the need for an additional
      navigation or balancing device. The surgical technique for all types of knee
      resurfacement comprises the steps of cartilage removal, knee balancing in
      extension and flexion, sparing bony cuts, final preparation of femur and tibia,
      trialling, cementing of components and final choice of tibial insert. The use of
      individualized three-dimensional image-derived resurfacing implants, as well as
      personalized single-use instrumentation, facilitates the surgeon to perform an
      almost anatomical knee resurfacement that has the potential to restore almost
      normal knee kinematics. The limited data on this novel technology is promising,
      however long-term clinical data is needed for final evaluation of this
      technology. 

PMID- 25860120
TI  - [Arthroplasty for osteoarthritis secondary to hip dysplasia: Problem-oriented
      treatment strategies].
AB  - BACKGROUND: Because of anatomical variations total hip arthroplasty (THA) can be
      demanding in patients with osteoarthritis secondary to hip dysplasia. OBJECTIVES:
      Depending on the degree of bony deformation, hip dislocation and soft tissue
      alteration numerous treatment strategies are available. This review describes
      current approaches that address frequent deformities. MATERIALS AND METHODS:
      Review of relevant clinical studies, meta-analyses, and presentation of our own
      approach. RESULTS: Pre-operative planning (based on a thorough clinical and
      radiographic examination) is essential. Acetabular reconstruction close to the
      primary acetabulum should always be intended. Roof augmentation and/or cup
      medialization can support stable bony implant fixation. Subtrochanteric
      shortening osteotomy of the femur is a demanding but reliable technique that
      avoids nerve damage in cases where inappropriate lengthening would be necessary
      (i.e., high riding dislocation). CONCLUSIONS: Although the post-operative
      complication rate is elevated after THA for dysplastic hips compared with primary
      osteoarthritis, the overall functional results and implant survival are
      comparable.

PMID- 25860121
TI  - Titania-catalyzed radiofluorination of tosylated precursors in highly aqueous
      medium.
AB  - Nucleophilic radiofluorination is an efficient synthetic route to many positron
      emission tomography (PET) probes, but removal of water to activate the cyclotron
      produced [(18)F]fluoride has to be performed prior to reaction, which
      significantly increases overall radiolabeling time and causes radioactivity loss.
      In this report, we demonstrate the possibility of (18)F-radiofluorination in
      highly aqueous medium. The method utilizes titania nanoparticles, 1:1 (v/v)
      acetonitrile-thexyl alcohol solvent mixture, and tetra-n-butylammonium
      bicarbonate as a phase-transfer agent. Efficient radiolabeling is directly
      performed with aqueous [(18)F]fluoride without the need for a drying/azeotroping
      step to significantly reduce radiosynthesis time. High radiochemical purity of
      the target compound is also achieved. The substrate scope of the synthetic
      strategy is demonstrated with a range of aromatic, aliphatic, and cycloaliphatic
      tosylated precursors. 

PMID- 25860122
TI  - Evaluation of a Novel Tc-99m Labelled Vitamin B12 Derivative for Targeting
      Escherichia coli and Staphylococcus aureus In Vitro and in an Experimental
      Foreign-Body Infection Model.
AB  - PURPOSE: Vitamin B12 (cyanocobalamin, Cbl) is accumulated by rapidly replicating
      prokaryotic and eukaryotic cells. We investigated the potential of a Tc-99m
      labelled Cbl derivative ([(99m)Tc]PAMA(4)-Cbl) for targeting infections caused by
      Escherichia coli and Staphylococcus aureus. In vitro binding assays were followed
      by biodistribution studies in a mouse model of foreign body infection.
      PROCEDURES: E. coli (ATCC 25922) and S. aureus (ATCC 43335) were used as test
      strains. [(57)Co]Cbl, [(67)Ga]citrate and [(99m)Tc]DTPA served as reference
      compounds. The in vitro competitive binding of [(57)Co]Cbl or [(99m)Tc]PAMA(4)
      Cbl, and unlabeled Cbl, to viable or killed bacteria, was evaluated at 37 and 4 
      degrees C. A cage mouse model of infection was used for biodistribution of
      intravenous [(57)Co]Cbl and [(99m)Tc]PAMA(4)-Cbl in cage and dissected tissues of
      infected and non-infected mice. RESULTS: Maximum binding (mean +/- SD) of
      [(57)Co]Cbl to viable E. coli was 81.7 +/- 2.6 % and to S. aureus 34.0 +/- 6.7 %,
      at 37  degrees C; no binding occurred to heat-killed bacteria. Binding to both
      test strains was displaced by 100- to 1000-fold excess of unlabeled Cbl. The in
      vitro binding of [(99m)Tc]PAMA(4)-Cbl was 100-fold and 3-fold lower than the one
      of [(57)Co]Cbl for E. coli and S. aureus, respectively. In vivo, [(99m)Tc]PAMA(4)
      Cbl showed peak percentage of injected dose (% ID) values between 1.33 and 2.3,
      at 30 min post-injection (p.i.). Significantly higher retention occurred in cage
      fluids infected with S. aureus at 4 h and with E. coli at 8 h p.i. than in non
      infected animals. Accumulation into infected cages was also higher than the one
      of [(99m)Tc]DTPA, which showed similar biodistribution in infected and sterile
      mice. [(57)Co]Cbl gradually accumulated in cages with peaks % ID between 3.58 and
      4.83 % achieved from 24 to 48 h. Discrimination for infection occurred only in E.
      coli-infected mice, at 72 h p.i. [(67)Ga]citrate, which showed a gradual
      accumulation into cage fluids during 12 h, was discriminative for infection from
      48 to 72 h p.i. (P < 0.05). CONCLUSION: Cbl displayed rapid and specific in vitro
      binding to test strains. [(99m)Tc]PAMA(4)-Cbl was rapidly cleared from most
      tissues and discriminated between sterile and infected cages, being a promising
      candidate for imaging infections in humans.

PMID- 25860124
TI  - L-sorbose is not only a substrate for 2-keto-L-gulonic acid production in the
      artificial microbial ecosystem of two strains mixed fermentation.
AB  - The co-culture system of the fermentation process of vitamin C can be regarded as
      an artificial microbial ecosystem (AME). To extend our understanding of this AME,
      an investigation of the relationship between strains, substrate and product was
      carried out in this study. The results showed that both Ketogulonicigenium
      vulgare and 2-keto-L-gulonic acid (2-KLG, the precursor of vitamin C) can inhibit
      the growth of the helper strain, while the helper strain promoted the growth of
      K. vulgare and 2-KLG production. Moreover, L-sorbose is not only a substrate for
      2-KLG production in the AME, but also a promoter of K. vulgare and an inhibitor
      of the helper strain. In the earlier stage of fermentation, the inhibition of L
      sorbose on the helper strain's growth is a key factor for ensuring an efficient
      fermentation. In the condition of adding the extra helper strain (OD: 0.57, ratio
      of inoculation: 2%), the yields of 2-KLG is increased by 9% in the 14% L-sorbose
      medium. To the best of our knowledge, this is the first report about the
      inhibition of substrate in the AME of 2-KLG production.

PMID- 25860123
TI  - Whole-genome sequencing of Bacillus subtilis XF-1 reveals mechanisms for
      biological control and multiple beneficial properties in plants.
AB  - Bacillus subtilis XF-1 is a gram-positive, plant-associated bacterium that
      stimulates plant growth and produces secondary metabolites that suppress soil
      borne plant pathogens. In particular, it is especially highly efficient at
      controlling the clubroot disease of cruciferous crops. Its 4,061,186-bp genome
      contains an estimated 3853 protein-coding sequences and the 1155 genes of XF-1
      are present in most genome-sequenced Bacillus strains: 3757 genes in B. subtilis
      168, and 1164 in B. amyloliquefaciens FZB42. Analysis using the Cluster of
      Orthologous Groups database of proteins shows that 60 genes control bacterial
      mobility, 221 genes are related to cell wall and membrane biosynthesis, and more
      than 112 are genes associated with secondary metabolites. In addition, the genes
      contributed to the strain's plant colonization, bio-control and stimulation of
      plant growth. Sequencing of the genome is a fundamental step for developing a
      desired strain to serve as an efficient biological control agent and plant growth
      stimulator. Similar to other members of the taxon, XF-1 has a genome that
      contains giant gene clusters for the non-ribosomal synthesis of antifungal
      lipopeptides (surfactin and fengycin), the polyketides (macrolactin and
      bacillaene), the siderophore bacillibactin, and the dipeptide bacilysin. There
      are two synthesis pathways for volatile growth-promoting compounds. The
      expression of biosynthesized antibiotic peptides in XF-1 was revealed by matrix
      assisted laser desorption/ionization-time of flight mass spectrometry. 

PMID- 25860125
TI  - Pilot studies on scale-up biocatalysis of 7-beta-xylosyl-10-deacetyltaxol and its
      analogues by an engineered yeast.
AB  - Paclitaxel content in yew tree is extremely low, causing a worldwide shortage of
      this important anticancer drug. Yew tree can also produce abundant 7-beta-xylosyl
      10-deacetyltaxol that can be bio-converted into 10-deacetyltaxol for semi
      synthesis of paclitaxel. However, the bio-conversion by the screened natural
      microorganisms was inefficient. We have constructed the recombinant yeast with a
      glycoside hydrolase gene from Lentinula edodes and explored the bioconversion.
      Based on previously established reaction conditions, the bioconversion of 7-beta
      xylosyl-10-deacetyltaxol or its extract was further optimized and scaled up with
      the engineered yeast harvested from 200-L scale high-cell-density fermentation.
      The optimization included the freeze-dried cell amount, dimethyl sulfoxide
      concentration, addition of 0.5% antifoam supplement, and substrate concentration.
      A 93-95% bioconversion and 83% bioconversion of 10 and 15 g/L 7-beta
      xylosyltaxanes in 10 L reaction volume were achieved, respectively. The yield of
      10-deacetyltaxol reached 10.58 g/L in 1 L volume with 15 g/L 7-beta-xylosyl-10
      deacetyltaxol. The conversion efficiencies were not only much higher than those
      of other reports and our previous work, but also realized in 10 L reaction
      volume. A pilot-scale product purification was also established. Our study
      bridges the gap between the basic research and commercial utilization of 7-beta
      xylosyl-10-deacetyltaxol for the industrial production of semi-synthetic
      paclitaxel.

PMID- 25860126
TI  - Carbetocin at Cesarean delivery for labour arrest: a sequential allocation trial
      to determine the effective dose.
AB  - PURPOSE: The aim of this study was to estimate the effective dose 90% (ED90) of
      carbetocin to provide adequate uterine tone at Cesarean delivery (CD) for labour
      arrest. METHODS: We conducted a double-blind dose-finding study of carbetocin
      using a biased-coin up-and-down design in women undergoing CD for labour arrest
      under epidural anesthesia. Forty healthy term pregnant women who had received at
      least three hours of oxytocin infusion during labour were recruited for the
      study. Carbetocin was administered intravenously upon delivery of the anterior
      shoulder of the fetus. The first patient received 20 ug, and the dose for the
      subsequent patient was determined according to the response of the previous
      patient as per the biased-coin allocation scheme using increments or decrements
      of 20 ug (maximum 140 ug). Uterine tone was assessed by the obstetrician and
      rated as satisfactory or unsatisfactory throughout the intraoperative period. The
      primary outcome was satisfactory uterine tone with no need for additional
      uterotonic drugs intraoperatively. Secondary outcomes included use of additional
      uterotonic drugs postoperatively in the first 24 hr, estimated blood loss, and
      adverse effects. RESULTS: The ED90 of carbetocin to produce adequate uterine tone
      was estimated at 121 ug (95% confidence interval [CI]: 111 to 130; 99% CI: 108 to
      133) using the truncated Dixon and Mood (DM) method. The isotonic estimator of
      ED90 was 140 ug; however, the observed response rate across all doses was < 90%.
      Also, the 95% CI of the DM estimator is likely to have lower than expected
      coverage, while the 99% CI may have about 90% coverage. Therefore, these results
      should be interpreted with caution. The overall median (range) estimated blood
      loss was 1,014 (104-2,436) mL. The overall incidence of hypotension and
      tachycardia were 45% and 57.5%, respectively. At a dose of 140 ug, the incidence
      of tachycardia and intraoperative arrhythmias was 76% and 14%, respectively.
      CONCLUSION: The ED90 of carbetocin at CD for labour arrest, as determined in our
      study, should be interpreted with caution since it may be underestimated. This
      dose is higher than the currently recommended dose of 100 ug at elective CD and
      should not be used routinely given the uncertainty regarding its efficacy and the
      high incidence of arrhythmias at higher doses. This trial was registered at
      ClinicalTrials.gov, number: NCT01725243.

PMID- 25860127
TI  - Undiagnosed vertebral hemangioma causing a lumbar compression fracture and
      epidural hematoma in a parturient undergoing vaginal delivery under epidural
      analgesia: a case report.
AB  - INTRODUCTION: Vertebral hemangiomas are benign vascular tumours of the bony spine
      which are usually asymptomatic. Pregnancy-related anatomical and hormonal changes
      may lead to expansion of hemangiomas and development of neurological symptoms. We
      present an unusual case of vertebral fracture due to an undiagnosed hemangioma
      presenting as postpartum back pain following epidural analgesia. CASE
      PRESENTATION: A multiparous female with an unremarkable history developed intense
      lumbar pain after vaginal delivery under epidural analgesia. The pain was
      attributed to tissue trauma associated with the epidural technique. The patient
      had no clinical improvement with analgesics, and her symptoms deteriorated over
      the following days. A magnetic resonance imaging scan revealed an acute fracture
      of the second lumbar vertebra (L2) with epidural extension and mild compression
      of the dural sac, suggesting hemangioma as the underlying cause. The patient
      underwent successful spinal surgery with pedicle screw fixation to stabilize the
      fracture. CONCLUSION: Vertebral fractures secondary to acute expansion of a
      vertebral hemangioma rarely occur during vaginal delivery. In such cases, the
      labour epidural technique and analgesia may challenge the physician in making the
      diagnosis. Postpartum severe back pain should be thoroughly investigated even in
      the absence of neurological deficits, and osseous spinal pathology should be
      considered in the differential diagnosis.

PMID- 25860129
TI  - Interfacial tension does not drive asymmetric nanoscale electrowetting on
      graphene.
AB  - We report molecular dynamics simulations of the electrowetting behavior of
      liquids in confinement between two oppositely charged graphene sheets. We observe
      that changes in the static contact angles of water, salty (4 M NaCl) water, and 1
      butyl-3-methylimidazolium tetrafluoroborate ([bmim][BF4]) (a room temperature
      ionic liquid) exhibit an asymmetric dependence on electric field polarity. The
      solid-liquid interfacial tension, which is expected to drive these changes, has
      been calculated independently by integrating the reversible work performed upon
      introducing positive and negative surface charges. This quantity shows either no
      dependence on the polarity of the electric field (water) or a dependence exactly
      opposite to the one obtained by applying the Young-Lippmann equation to the
      observed contact angles ([bmim][BF4]). Our analysis indicates that the observed
      contact angle asymmetry finds its origin in the liquid structure in the vicinity
      of the three-phase contact line. In particular, it is suggested that the
      molecular orientation properties are crucial to determine the asymmetric wetting
      behavior of pure water; in addition, the contrast in the strength of the ion
      hydration shells has a decisive influence on the NaCl solution behavior. 

PMID- 25860128
TI  - Characterization of the loss of SUMO pathway function on cancer cells and tumor
      proliferation.
AB  - SUMOylation is a post-translational ubiquitin-like protein modification pathway
      that regulates important cellular processes including chromosome structure,
      kinetochore function, chromosome segregation, nuclear and sub-nuclear
      organization, transcription and DNA damage repair. There is increasing evidence
      that the SUMO pathway is dysregulated in cancer, raising the possibility that
      modulation of this pathway may have therapeutic potential. To investigate the
      importance of the SUMO pathway in the context of cancer cell proliferation and
      tumor growth, we applied lentivirus-based short hairpin RNAs (shRNA) to knockdown
      SUMO pathway genes in human cancer cells. shRNAs for SAE2 and UBC9 reduced SUMO
      conjugation activity and inhibited proliferation of human cancer cells. To expand
      upon these observations, we generated doxycycline inducible conditional shRNA
      cell lines for SAE2 to achieve acute and reversible SAE2 knockdown. Conditional
      SAE2 knockdown in U2OS and HCT116 cells slowed cell growth in vitro, and SAE2
      knockdown induced multiple terminal outcomes including apoptosis,
      endoreduplication and senescence. Multinucleated cells became senescent and
      stained positive for the senescence marker, SA-beta Gal, and displayed elevated
      levels of p53 and p21. In an attempt to explain these phenotypes, we confirmed
      that loss of SUMO pathway activity leads to a loss of SUMOylated Topoisomerase
      IIalpha and the appearance of chromatin bridges which can impair proper
      cytokinesis and lead to multinucleation. Furthermore, knockdown of SAE2 induces
      disruption of PML nuclear bodies which may further promote apoptosis or
      senescence. In an in vivo HCT116 xenograft tumor model, conditional SAE2
      knockdown strongly impaired tumor growth. These data demonstrate that the SUMO
      pathway is required for cancer cell proliferation in vitro and tumor growth in
      vivo, implicating the SUMO pathway as a potential cancer therapeutic target. 

PMID- 25860130
TI  - Memantine monotherapy for Alzheimer's disease: a systematic review and meta
      analysis.
AB  - BACKGROUND: We performed an updated meta-analysis of randomized placebo
      controlled trials testing memantine monotherapy for patients with Alzheimer's
      disease (AD). METHODS: The meta-analysis included randomized controlled trials of
      memantine monotherapy for AD, omitting those in which patients were also
      administered a cholinesterase inhibitor. Cognitive function, activities of daily
      living, behavioral disturbances, global function, stage of dementia, drug
      discontinuation rate, and individual side effects were compared between memantine
      monotherapy and placebo groups. The primary outcomes were cognitive function and
      behavioral disturbances; the others were secondary outcomes. RESULTS: Nine
      studies including 2433 patients that met the study's inclusion criteria were
      identified. Memantine monotherapy significantly improved cognitive function
      [standardized mean difference (SMD)=-0.27, 95% confidence interval (CI)=-0.39 to 
      0.14, p=0.0001], behavioral disturbances (SMD=-0.12, 95% CI=-0.22 to -0.01,
      p=0.03), activities of daily living (SMD=-0.09, 95% CI=-0.19 to -0.00, p=0.05),
      global function assessment (SMD=-0.18, 95% CI=-0.27 to -0.09, p=0.0001), and
      stage of dementia (SMD=-0.23, 95% CI=-0.33 to -0.12, p=0.0001) scores. Memantine
      was superior to placebo in terms of discontinuation because of inefficacy [risk
      ratio (RR)=0.36, 95% CI=0.17! to 0.74, p=0.006, number needed to harm (NNH)=non
      significant]. Moreover, memantine was associated with less agitation compared
      with placebo (RR=0.68, 95% CI=0.49 to 0.94, p=0.02, NNH=non significant). There
      were no significant differences in the rate of discontinuation because of all
      causes, all adverse events, and individual side effects other than agitation
      between the memantine monotherapy and placebo groups. CONCLUSIONS: Memantine
      monotherapy improved cognition, behavior, activities of daily living, global
      function, and stage of dementia and was well-tolerated by AD patients. However,
      the effect size in terms of efficacy outcomes was small and thus there is limited
      evidence of clinical benefit.

PMID- 25860131
TI  - Characterization of the kidney transcriptome of the long-haired mouse Abrothrix
      hirta (Rodentia, Sigmodontinae) and comparison with that of the olive mouse A.
      olivacea.
AB  - To understand how small mammals cope with the challenge of water homeostasis is a
      matter of interest for ecologists and evolutionary biologists. Here we take a
      step towards the understanding of the transcriptomic functional response of
      kidney using as a model the long-haired mouse (Abrothrix hirta) a species that
      distributes across Patagonian steppes and Austral temperate rainforests in
      Argentina and Chile. Specifically, we i) characterize the renal transcriptome of
      A. hirta, and ii) compare it with that-already available-of the co-generic and co
      distributed A. olivacea. Renal mRNA transcripts from 16 specimens of A. hirta
      from natural populations were analyzed. Over 500 million Illumina paired-end
      reads were assembled de novo under two approaches, an individual assembly for
      each specimen, and a single in-silico normalized joint assembly including all
      reads from all specimens. The total number of annotated genes was similar with
      both strategies: an average of 14,956 in individual assemblies and 14,410 in the
      joint assembly. Overall, 15,463 distinct genes express in the kidney of A. hirta.
      Transcriptomes of A. hirta and A. olivacea were similar in terms of gene
      abundance and composition: 95.6% of the genes of A. hirta were also found in A.
      olivacea making their functional profiles also similar. However, differences in
      the transcriptome of these two species were observed in the set of highly
      expressed genes, in terms of private genes for each species and the functional
      profiles of highly expressed genes. As part of the novel transcriptome
      characterization, we provide distinct gene lists with their functional annotation
      that would constitute the basis for further research on these or any other
      species of the subfamily Sigmodontinae, which includes about 400 living species
      distributed from Tierra del Fuego to southern United States. 

PMID- 25860133
TI  - Aneurysms: foreword.

PMID- 25860132
TI  - Response to letter to the editor Re: The effect of PPI use on human gut
      microbiota and weight loss in patients undergoing laparoscopic Roux-en-Y gastric
      bypass.

PMID- 25860134
TI  - Aneurysms: intracranial aneurysms.
AB  - Intracranial aneurysms (IAs) are found in 3.2% of the general population and most
      commonly are diagnosed in individuals at a mean age of 50 years. Most IAs occur
      in the internal carotid circulation. When an IA ruptures and causes subarachnoid
      hemorrhage, patients typically present with severe thunderclap headaches. When
      aneurysmal rupture is suspected, noncontrast computed tomography scan of the head
      is indicated. If subarachnoid hemorrhage is confirmed, the patient should be
      referred to a center that offers neurosurgical and critical care for short- and
      long-term management. A computed tomography angiogram is then obtained to define
      anatomy. Nonoperative components of management include blood pressure control,
      antifibrinolytics, calcium channel blockers, statins, and an anticonvulsant for
      seizure prophylaxis. Definitive treatment involves endovascular procedures (eg,
      coil embolization) or microvascular surgery (eg, clipping the base of the
      aneurysm), with the choice depending on patient age, comorbidities, and IA
      anatomy. In some patients, aneurysms are detected before rupture, such as via
      imaging studies obtained for other reasons. In such cases, monitoring of
      unruptured anterior circulation IAs with interval magnetic resonance angiography
      is recommended if the aneurysm is smaller than 7 mm. Larger IAs and posterior
      circulation IAs typically warrant endovascular or microvascular procedures to
      prevent subarachnoid hemorrhage. 

PMID- 25860135
TI  - Aneurysms: abdominal aortic aneurysms.
AB  - Ruptured abdominal aortic aneurysms (AAAs) cause approximately 16,000 deaths per
      year in the United States. Smoking, male sex, advanced age, hypertension, and
      family history are risk factors. AAAs suspected on physical examination should be
      evaluated with ultrasonography. In addition, ultrasonography screening for AAA is
      recommend for men ages 65 to 75 years with smoking histories. For men ages 65 to
      75 years who have never smoked, screening should be performed selectively, such
      as for those with family histories of AAA. Screening women currently is not
      recommended, regardless of smoking status. Surgical repair is indicated for men
      with AAA diameters of 5.5 cm or greater. The common practice for women is to
      repair AAAs with diameters of 5.0 cm or greater. For patients with smaller AAAs,
      cardiac risk factor management is recommended along with interval ultrasonography
      monitoring. Surgery is indicated if monitoring shows that an AAA is enlarging (by
      1 cm or more per year) or reaches the noted limits. Repair of AAA (ruptured or
      unruptured) is accomplished with open surgery or endovascular procedures (eg,
      transcatheter placement of a stent graft). Endovascular procedures are now used
      more frequently than open surgery and have similar outcomes. 

PMID- 25860136
TI  - Aneurysms: thoracic aortic aneurysms.
AB  - Thoracic aortic aneurysms (TAAs) have many possible etiologies, including
      congenital heart defects (eg, bicuspid aortic valves, coarctation of the aorta),
      inherited connective tissue disorders (eg, Marfan, Ehlers-Danlos, Loeys-Dietz
      syndromes), and degenerative conditions (eg, medial necrosis, atherosclerosis of
      the aortic wall). Symptoms of rupture include a severe tearing pain in the chest,
      back, or neck, sometimes associated with cardiovascular collapse. Before rupture,
      TAAs may exert pressure on other thoracic structures, leading to a variety of
      symptoms. However, most TAAs are asymptomatic and are found incidentally during
      imaging for other conditions. Diagnosis is confirmed with computed tomography
      scan or echocardiography. Asymptomatic TAAs should be monitored with imaging at
      specified intervals and patients referred for repair if the TAAs are enlarging
      rapidly (greater than 0.5 cm in diameter over 6 months for heritable etiologies;
      greater than 0.5 cm over 1 year for degenerative etiologies) or reach a critical
      aortic diameter threshold for elective surgery (5.5 cm for TAAs due to
      degenerative etiologies, 5.0 cm when associated with inherited syndromes). Open
      surgery is used most often to treat asymptomatic TAAs in the ascending aorta and
      aortic arch. Asymptomatic TAAs in the descending aorta often are treated
      medically with aggressive blood pressure control, though recent data suggest that
      endovascular procedures may result in better long-term survival rates. 

PMID- 25860137
TI  - Aneurysms: popliteal and visceral artery aneurysms.
AB  - Popliteal artery aneurysms (PAAs) occur in approximately 1 of every 100 men ages
      65 to 80 years. They can occur bilaterally, and abdominal aortic aneurysm is
      simultaneously present in 50% of cases. Therefore, patients with PAAs should
      undergo ultrasonography to exclude abdominal aortic aneurysms and contralateral
      PAAs. The main risk of PAAs is thrombus/embolus formation causing lower limb
      ischemia. Any symptomatic PAA or PAA containing a thrombus should be repaired
      regardless of size. Asymptomatic PAAs should be considered for repair if the
      diameter is 2 cm or greater. Visceral artery aneurysms are rare and typically are
      diagnosed incidentally during imaging for other conditions. The most common is
      splenic artery (SA) aneurysm, but aneurysms also occur in hepatic, mesenteric,
      celiac, and other arteries. Although uncommon and typically asymptomatic, SA
      aneurysms are significant because of rupture risk. Current recommendations are
      that SA aneurysms 2 cm or larger should be repaired. SA aneurysms of any size
      should be repaired in pregnant women and women of childbearing age because of the
      high maternal (75%) and fetal (95%) mortality rates associated with rupture.
      Superior mesenteric artery aneurysms should be repaired, regardless of size
      because of rupture risk. Other visceral artery aneurysms typically can be
      monitored and repaired if they reach 2 cm in diameter. 

PMID- 25860139
TI  - Who bites the bullet first? The susceptibility of leopards Panthera pardus to
      trophy hunting.
AB  - Reliable data is fundamentally important for managing large carnivore
      populations, and vital for informing hunting quota levels if those populations
      are subject to trophy hunting. Camera-trapping and spoor counts can provide
      reliable population estimates for many carnivores, but governments typically lack
      the resources to implement such surveys over the spatial scales required to
      inform robust quota setting. It may therefore be prudent to shift focus away from
      estimating population size and instead focus on monitoring population trend. In
      this paper we assess the susceptibility of African leopards Panthera pardus to
      trophy hunting. This has management ramifications, particularly if the use of
      harvest composition is to be explored as a metric of population trend. We explore
      the susceptibility of different leopard age and sex cohorts to trophy hunting;
      first by examining their intrinsic susceptibility to encountering trophy hunters
      using camera-traps as surrogates, and second by assessing their extrinsic
      susceptibility using photographic questionnaire surveys to determine their
      attractiveness to hunters. We show that adult male and female leopards share
      similar incident rates to encountering hunters but adult males are the most
      susceptible to hunting due to hunter preference for large trophies. In contrast,
      sub-adult leopards rarely encounter hunters and are the least attractive
      trophies. We suggest that our findings be used as a foundation for the
      exploration of a harvest composition scheme in the Kwazulu-Natal and Limpopo
      provinces where post mortem information is collected from hunted leopards and
      submitted to the local provincial authorities. 

PMID- 25860138
TI  - Functional characterization of human T cell hyporesponsiveness induced by CTLA4
      Ig.
AB  - During activation, T cells integrate multiple signals from APCs and cytokine
      milieu. The blockade of these signals can have clinical benefits as exemplified
      by CTLA4-Ig, which blocks interaction of B7 co-stimulatory molecules on APCs with
      CD28 on T cells. Variants of CTLA4-Ig, abatacept and belatacept are FDA approved
      as immunosuppressive agents in arthritis and transplantation, yet murine studies
      suggested that CTLA4-Ig could be beneficial in a number of other diseases.
      However, detailed analysis of human CD4 cell hyporesponsivness induced by CTLA4
      Ig has not been performed. Herein, we established a model to study the effect of
      CTLA4-Ig on the activation of human naive T cells in a human mixed lymphocytes
      system. Comparison of human CD4 cells activated in the presence or absence of
      CTLA4-Ig showed that co-stimulation blockade during TCR activation does not
      affect NFAT signaling but results in decreased activation of NF-kappaB and AP-1
      transcription factors followed by a profound decrease in proliferation and
      cytokine production. The resulting T cells become hyporesponsive to secondary
      activation and, although capable of receiving TCR signals, fail to proliferate or
      produce cytokines, demonstrating properties of anergic cells. However, unlike
      some models of T cell anergy, these cells did not possess increased levels of the
      TCR signaling inhibitor CBLB. Rather, the CTLA4-Ig-induced hyporesponsiveness was
      associated with an elevated level of p27kip1 cyclin-dependent kinase inhibitor. 

PMID- 25860140
TI  - Cascading walks model for human mobility patterns.
AB  - BACKGROUND: Uncovering the mechanism behind the scaling laws and series of
      anomalies in human trajectories is of fundamental significance in understanding
      many spatio-temporal phenomena. Recently, several models, e.g. the explorations
      returns model (Song et al., 2010) and the radiation model for intercity travels
      (Simini et al., 2012), have been proposed to study the origin of these anomalies
      and the prediction of human movements. However, an agent-based model that could
      reproduce most of empirical observations without priori is still lacking.
      METHODOLOGY/PRINCIPAL FINDINGS: In this paper, considering the empirical findings
      on the correlations of move-lengths and staying time in human trips, we propose a
      simple model which is mainly based on the cascading processes to capture the
      human mobility patterns. In this model, each long-range movement activates series
      of shorter movements that are organized by the law of localized explorations and
      preferential returns in prescribed region. CONCLUSIONS/SIGNIFICANCE: Based on the
      numerical simulations and analytical studies, we show more than five statistical
      characters that are well consistent with the empirical observations, including
      several types of scaling anomalies and the ultraslow diffusion properties,
      implying the cascading processes associated with the localized exploration and
      preferential returns are indeed a key in the understanding of human mobility
      activities. Moreover, the model shows both of the diverse individual mobility and
      aggregated scaling displacements, bridging the micro and macro patterns in human
      mobility. In summary, our model successfully explains most of empirical findings
      and provides deeper understandings on the emergence of human mobility patterns.

PMID- 25860142
TI  - Individualizing risk of multidrug-resistant pathogens in community-onset
      pneumonia.
AB  - INTRODUCTION: The diffusion of multidrug-resistant (MDR) bacteria has created the
      need to identify risk factors for acquiring resistant pathogens in patients
      living in the community. OBJECTIVE: To analyze clinical features of patients with
      community-onset pneumonia due to MDR pathogens, to evaluate performance of
      existing scoring tools and to develop a bedside risk score for an early
      identification of these patients in the Emergency Department. PATIENTS AND
      METHODS: This was an open, observational, prospective study of consecutive
      patients with pneumonia, coming from the community, from January 2011 to January
      2013. The new score was validated on an external cohort of 929 patients with
      pneumonia admitted in internal medicine departments participating at a
      multicenter prospective study in Spain. RESULTS: A total of 900 patients were
      included in the study. The final logistic regression model consisted of four
      variables: 1) one risk factor for HCAP, 2) bilateral pulmonary infiltration, 3)
      the presence of pleural effusion, and 4) the severity of respiratory impairment
      calculated by use of PaO2/FiO2 ratio. A new risk score, the ARUC score, was
      developed; compared to Aliberti, Shorr, and Shindo scores, this point score
      system has a good discrimination performance (AUC 0.76, 95% CI 0.71-0.82) and
      calibration (Hosmer-Lemeshow, chi2 = 7.64; p = 0.469). The new score outperformed
      HCAP definition in predicting etiology due to MDR organism. The performance of
      this bedside score was confirmed in the validation cohort (AUC 0.68, 95% CI 0.60
      0.77). CONCLUSION: Physicians working in ED should adopt simple risk scores, like
      ARUC score, to select the most appropriate antibiotic regimens. This
      individualized approach may help clinicians to identify those patients who need
      an empirical broad-spectrum antibiotic therapy.

PMID- 25860143
TI  - Control of trachoma in Australia: a model based evaluation of current
      interventions.
AB  - BACKGROUND: Australia is the only high-income country in which endemic trachoma
      persists. In response, the Australian Government has recently invested heavily
      towards the nationwide control of the disease. METHODOLOGY/PRINCIPAL FINDINGS: A
      novel simulation model was developed to reflect the trachoma epidemic in
      Australian Aboriginal communities. The model, which incorporates demographic,
      migration, mixing, and biological heterogeneities, was used to evaluate recent
      intervention measures against counterfactual past scenarios, and also to assess
      the potential impact of a series of hypothesized future intervention measures
      relative to the current national strategy and intensity. The model simulations
      indicate that, under the current intervention strategy and intensity, the
      likelihood of controlling trachoma to less than 5% prevalence among 5-9 year-old
      children in hyperendemic communities by 2020 is 31% (19%-43%). By shifting
      intervention priorities such that large increases in the facial cleanliness of
      children are observed, this likelihood of controlling trachoma in hyperendemic
      communities is increased to 64% (53%-76%). The most effective intervention
      strategy incorporated large-scale antibiotic distribution programs whilst
      attaining ambitious yet feasible screening, treatment, facial cleanliness and
      housing construction targets. Accordingly, the estimated likelihood of
      controlling trachoma in these communities is increased to 86% (76%-95%).
      CONCLUSIONS/SIGNIFICANCE: Maintaining the current intervention strategy and
      intensity is unlikely to be sufficient to control trachoma across Australia by
      2020. However, by shifting the intervention strategy and increasing intensity,
      the likelihood of controlling trachoma nationwide can be significantly increased.

PMID- 25860144
TI  - Adjunctive medical therapy with alpha-blocker after extracorporeal shock wave
      lithotripsy of renal and ureteral stones: a meta-analysis.
AB  - BACKGROUND: Although some trials assessed the efficacy and safety of the alpha
      blocker in facilitating renal and ureteral stones expulsion after extracorporeal
      shock wave lithotripsy (ESWL), the role of the alpha-blocker in facilitating
      upper urinary calculi expulsion after ESWL remain controversial. AIMS: To
      determine the efficacy and safety of the alpha-blocker in facilitating renal and
      ureteral stones expulsion after ESWL. METHODS: A literature search was carried
      out using the PubMed database, EMBASE and the Cochrane Library database to
      identify relevant studies. Two reviewers independently extracted data and
      assessed methodological quality. Pooled effect estimates were obtained using a
      fixed- and random-effects meta-analysis. RESULTS: The meta-analysis included 23
      RCTs, alpha-blocker significantly enhanced expulsion rate of upper urinary tract
      calculi after ESWL (P<0.00001; RR 1.21; 95% CI 1.12-1.31), significantly promoted
      steinstrasse expulsion (P=0.03; RR 1.25; 95% CI 1.03-1.53), significantly
      shortened the discharge time of upper urinary tract calculi (P=0.0001; MD -2.12;
      95% CI -3.20--1.04), significantly reduced the patient's pain VAS score (P=0.001;
      RR -1.0; 95% CI -1.61--0.39). Compared with the control group, dizziness
      (P=0.002; RR 5.48; 95% CI 1.91-15.77), anejaculation (P=0.02; RR 12.17; 95% CI
      1.61-91.99) and headache (P=0.04; RR 4.03; 95% CI 1.04-15.72) in the alpha
      blocker group was associated with a higher incidence. CONCLUSIONS: Treatment with
      alpha-blocker after ESWL appears to be effective in enhancing expulsion rate of
      upper urinary tract calculi, shortening the discharge time of upper urinary tract
      calculi, reducing the patient's pain. The side effects of alpha-blocker were
      light and few.

PMID- 25860145
TI  - Serum levels of the cancer-testis antigen POTEE and its clinical significance in
      non-small-cell lung cancer.
AB  - BACKGROUND: POTEE (POTE ankyrin domain family, member E) is a newly identified
      cancer-testis antigen that has been found to be expressed in a wide variety of
      human cancers including cancers of the colon, prostate, lung, breast, ovary, and
      pancreas. AIM: To measure the serum levels of POTEE in patients with non-small
      cell lung cancer (NSCLC) and to explore the clinical significance of POTEE in
      NSCLC. PATIENTS AND METHODS: 104 NSCLC patients, 66 benign lung disease patients
      and 80 healthy volunteers were enrolled in this study from May 2013 to February
      2014. Serum POTEE levels were measured using enzyme-linked immunosorbent assay
      (ELISA). Numerical variables were recorded as means +/- standard deviation (SD)
      and analyzed by independent t tests. Categorical variables were calculated as
      rates and were analyzed using a chi2 test or Fisher's exact test. Survival curves
      were estimated and compared using the Kaplan-Meier method and log-rank tests.
      RESULTS: Serum POTEE levels were significantly higher in NSCLC patients than in
      benign lung disease patients and healthy controls (mean +/- SD [pg/ml], 324.38+/-
      13.84 vs. 156.93 +/- 17.38 and 139.09 +/- 15.80, P<0.001) and were significantly
      correlated with TNM stage. Survival analysis revealed that patients with low
      serum POTEE had longer progression-free survival (PFS) than those with high serum
      POTEE (P=0.021). Cox multivariate analysis indicated that POTEE was an
      independent prognostic factor of progression-free survival (P =0.009, hazard
      ratio, 2.440). CONCLUSIONS: Serum POTEE level in NSCLC patients is associated
      with TNM stage and is a potential prognostic factor.

PMID- 25860146
TI  - Time course of immediate early gene protein expression in the spinal cord
      following conditioning stimulation of the sciatic nerve in rats.
AB  - Long-term potentiation induced by conditioning electrical stimulation of afferent
      fibers is a widely studied form of synaptic plasticity in the brain and the
      spinal cord. In the spinal cord dorsal horn, long-term potentiation is induced by
      a series of high-frequency trains applied to primary afferent fibers.
      Conditioning stimulation (CS) of sciatic nerve primary afferent fibers also
      induces expression of immediate early gene proteins in the lumbar spinal cord.
      However, the time course of immediate early gene expression and the rostral
      caudal distribution of expression in the spinal cord have not been systematically
      studied. Here, we examined the effects of sciatic nerve conditioning stimulation
      (10 stimulus trains, 0.5 ms stimuli, 7.2 mA, 100 Hz, train duration 2 s, 8 s
      intervals between trains) on cellular expression of immediate early genes, Arc, c
      Fos and Zif268, in anesthetized rats. Immunohistochemical analysis was performed
      on sagittal sections obtained from Th13- L5 segments of the spinal cord at 1, 2,
      3, 6 and 12 h post-CS. Strikingly, all immediate early genes exhibited a
      monophasic increase in expression with peak increases detected in dorsal horn
      neurons at 2 hours post-CS. Regional analysis showed peak increases at the
      location between the L3 and L4 spinal segments. Both Arc, c-Fos and Zif268
      remained significantly elevated at 2 hours, followed by a sharp decrease in
      immediate early gene expression between 2 and 3 hours post-CS. Colocalization
      analysis performed at 2 hours post-CS showed that all c-Fos and Zif268 neurons
      were positive for Arc, while 30% and 43% of Arc positive neurons were positive
      for c-Fos and Zif268, respectively. The present study identifies the spinal cord
      level and time course of immediate early gene (IEGP) expression of relevance for
      analysis of IEGPs function in neuronal plasticity and nociception. 

PMID- 25860147
TI  - Estimating mortality derived from indoor exposure to particles of outdoor origin.
AB  - Following an extensive review of the literature, we further analyze the published
      data to examine the health effects of indoor exposure to particulate matter (PM)
      of outdoor origin. We obtained data on all-cause, cardiovascular, and respiratory
      mortality per 10 MUg/m3 increase in outdoor PM10 or PM2.5; the infiltration
      factors for buildings; and estimated time spent outdoors by individuals in the
      United States, Europe, China, and globally. These data were combined log-linear
      exposure-response model to estimate the all-cause, cardiovascular, and
      respiratory mortality of exposure to indoor PM pollution of outdoor origin.
      Indoor PM pollution of outdoor origin is a cause of considerable mortality,
      accounting for 81% to 89% of the total increase in mortality associated with
      exposure to outdoor PM pollution for the studied regions. The findings suggest
      that enhancing the capacity of buildings to protect occupants against exposure to
      outdoor PM pollution has significant potential to improve public health outcomes.

PMID- 25860148
TI  - Response to goal management training in veterans with blast-related mild
      traumatic brain injury.
AB  - Veterans with blast-related mild traumatic brain injury (TBI) experience
      cognitive deficits that interfere with functional activities. Goal Management
      Training (GMT), which is a metacognitive intervention, offers an executive
      function rehabilitation approach that draws upon theories concerning goal
      processing and sustained attention. GMT has received empirical support in studies
      of patients with TBI but has not been tested in Veterans with blast-related mild
      TBI. GMT was modified from 7 weekly to 10 biweekly sessions. Participants
      included six combat Veterans that reported multiple blast exposures resulting in
      symptoms consistent with mild TBI. Group analysis showed a significant
      improvement in measures of executive function derived from performance on the
      computerized Tower of London. There were no significant changes on self/informant
      questionnaires of executive function, indicating a lack of generalization of
      improvement from the clinic to everyday activities. Overall, while the data
      indicate efficacy of GMT in the rehabilitation of combat Veterans with executive
      function deficits because of blast-related mild TBI, enhancement of
      generalization is needed. 

PMID- 25860150
TI  - [Incorporation to the academy of medicine: Dr. Marcelo Wolff Reyes].

PMID- 25860149
TI  - Global mapping of DNA conformational flexibility on Saccharomyces cerevisiae.
AB  - In this study we provide the first comprehensive map of DNA conformational
      flexibility in Saccharomyces cerevisiae complete genome. Flexibility plays a key
      role in DNA supercoiling and DNA/protein binding, regulating DNA transcription,
      replication or repair. Specific interest in flexibility analysis concerns its
      relationship with human genome instability. Enrichment in flexible sequences has
      been detected in unstable regions of human genome defined fragile sites, where
      genes map and carry frequent deletions and rearrangements in cancer. Flexible
      sequences have been suggested to be the determinants of fragile gene proneness to
      breakage; however, their actual role and properties remain elusive. Our in silico
      analysis carried out genome-wide via the StabFlex algorithm, shows the conserved
      presence of highly flexible regions in budding yeast genome as well as in genomes
      of other Saccharomyces sensu stricto species. Flexibile peaks in S. cerevisiae
      identify 175 ORFs mapping on their 3'UTR, a region affecting mRNA translation,
      localization and stability. (TA)n repeats of different extension shape the
      central structure of peaks and co-localize with polyadenylation efficiency
      element (EE) signals. ORFs with flexible peaks share common features. Transcripts
      are characterized by decreased half-life: this is considered peculiar of genes
      involved in regulatory systems with high turnover; consistently, their function
      affects biological processes such as cell cycle regulation or stress response.
      Our findings support the functional importance of flexibility peaks, suggesting
      that the flexible sequence may be derived by an expansion of canonical TAYRTA
      polyadenylation efficiency element. The flexible (TA)n repeat amplification could
      be the outcome of an evolutionary neofunctionalization leading to a differential
      3'-end processing and expression regulation in genes with peculiar function. Our
      study provides a new support to the functional role of flexibility in genomes and
      a strategy for its characterization inside human fragile sites. 

PMID- 25860151
TI  - [AIDS: a travel since impotent despair to the therapeutic success].

PMID- 25860152
TI  - [National Report: evolution of HIV/AIDS infection in Chile, 1984-2012].

PMID- 25860153
TI  - [Human immunodeficiency virus infection in children and adolescents: more of 25
      years in Chile].
AB  - In this article, the following topics about pediatric HIV infection and AIDS are
      summarized: a description of pathogenic and clinical aspects of HIV infection in
      children, the clues for its suspicion, the preventive strategies to avoid the
      vertical transmission of HIV, the study to certify or to rule out the HIV
      infection in infants and children, the main recommendations of antiretroviral
      treatment and how to prevent and treat manifestations of HIV infection. Besides,
      the evolution in Chile of the pediatric HIV infection is described with details,
      since the first child detected with AIDS in 1987, infected by transfusion and the
      first infants (twin) diagnosed in 1989, infected by vertical twins transmission,
      to 2014, with the progress obtained, snags, hopes and challenges addressed. 

PMID- 25860154
TI  - [Dermatologic manifestations associated with HIV/AIDS].
AB  - The ongoing human immunodeficiency virus (HIV) infection epidemic coupled with
      more efficacious and available treatments has led to a larger number of patients
      living with HIV or AIDS. As a result, skin manifestations related to HIV/AIDS or
      its therapy have become increasingly more common and are reported to occur in as
      many as 95% of patients. Herein, we review the most common HIV/AIDS related
      cutaneous pathologies and classify them into inflammatory, HAART-associated,
      neoplastic, and infectious manifestations. Cutaneous manifestations should be
      promptly recognized and treated by physicians and health care personnel in order
      to provide optimal care. 

PMID- 25860155
TI  - [Clinical and epidemiological characteristics of HIV infection in Latin-American
      immigrants: comparative analysis from clinical records in a clinical care centre
      in Santiago in the last decade].
AB  - BACKGROUND: There has been an increasing number of immigrants to Chile in the
      last years, especially from South American countries. The phenomenon of
      immigration and its consequences has been studied by international literature,
      and different health care needs have been reported for this group as compared
      with local population. In Chile this phenomenon is poorly studied and HIV
      prevention campaigns are focused on national population needs. OBJECTIVE: To
      determine baseline clinical and epidemiological characteristics of the HIV
      infection in Latin-American immigrants presenting to a referral HIV clinical care
      centre between the years 2003-2013. METHODS: Retrospective analysis. Baseline
      characteristics of Latin-American immigrants at admission to the infectious
      disease unit were compared to a peered group of Chileans in the same unit.
      RESULTS: There was an increase in the number of immigrants trough out the
      observation period. Foreigners presented larger proportion of women (26% vs. 9%)
      and heterosexual conduct as compared to nationals (37% vs 22%). The majority of
      immigrants came from Peru (55%) and Colombia (12%). CONCLUSIONS: There were
      significant differences in regards to gender and sexual behavior. This brings up
      the need to address different prevention strategies with more emphasis in women
      and heterosexual population in this vulnerable group.

PMID- 25860157
TI  - What lessons can be learned from failed Alzheimer's disease trials?
AB  - Trials missing primary efficacy end points raise the question of whether the
      choice of drug or the limitations of disease biology were at fault. In some
      trials, drugs appear not to have achieved biochemical effect thresholds
      sufficient for clinical benefit. This suggests the need for improved drugs that
      are more active at tolerated doses. In other trials, it is unclear how the
      observed biomarker changes are related to potential efficacy. However, hints of
      efficacy from exploratory analyses support the idea that starting treatment
      earlier in the course of the disease might be more effective. A closer look at
      the failed trials will help de-risk future trials. 

PMID- 25860156
TI  - Sonographic cross-sectional area measurement in carpal tunnel syndrome patients:
      can delta and ratio calculations predict severity compared to nerve conduction
      studies?
AB  - OBJECTIVE: To evaluate the accuracy of two different sonographic median nerve
      measurement calculations in predicting carpal tunnel syndrome (CTS) severity in a
      study population with clinically and electrophysiologically confirmed CTS.
      METHODS: 643 wrists of 427 patients (325 females and 102 males, age range: 17-90
      years, mean +/- SD: 57.9 +/- 14.7) were included with CTS diagnosis based on
      clinical and nerve conduction studies (NCS). Cross-sectional area (CSA)
      measurement of the median nerve was performed at the carpal tunnel level (CSAc)
      and at the pronator quadratus muscle level (CSAp). Two parameters were
      calculated: delta (?-CSA), which is the difference between proximal and distal
      measurements, and ratio (R-CSA), calculated by dividing distal over proximal
      measurements. RESULTS: Patients were classified into mild, moderate and severe
      CTS based upon NCS. The mean ?-CSA (4.2 +/- 2.6, 6.95 +/- 2.2 and 10.7 +/- 4.9
      mm(2)) and mean R-CSA (1.5 +/- 0.4, 1.95 +/- 0.4 and 2.4 +/- 0.7) values were
      significantly different between all groups (p < 0.001). Optimal cut-off values
      for ?-CSA and R-CSA were 6 mm(2) and 1.7, respectively, to distinguish mild from
      moderate disease, and 9 mm(2) and 2.2, respectively, to distinguish moderate from
      severe disease. CONCLUSION: Threshold values for the calculated sonographic
      parameters ?-CSA and R-CSA are useful in predicting CTS severity compared to NCS.
      KEY POINTS: * Two proposed parameters were calculated (?-CSA, R-CSA) and compared
      to NCS. * A defined sonoanatomical proximal landmark was used for the
      calculation. * Both parameters showed ability to detect CTS severity comparable
      to NCS. * Cut-off values could be determined for both parameters.

PMID- 25860158
TI  - Hysteretic Behavior upon Light Soaking in Perovskite Solar Cells Prepared via
      Modified Vapor-Assisted Solution Process.
AB  - Recently, the organic-inorganic hybrid perovskite solar cells exhibit rapidly
      rising efficiencies, while anomalous hysteresis in perovskite solar cells remains
      unsolvable. Herein, a high-quality perovskite thin film is prepared by a modified
      vapor-assisted solution process, which is a simple but well-controllable method
      proven to be capable of producing a thin film with full surface coverage and
      grain size up to micrometers. The as-fabricated perovskite solar cell has
      efficiency as high as 10.2%. The hysteresis effects of both planar and mesoscopic
      TiO2-based perovskite solar cells have been comprehensively studied upon
      illumination. The results demonstrate that mesoporous-based perovskite cells
      combined with remarkable grain size are subject to alleviating the hysteresis
      effects in comparison to the planar cells. Likewise, mesoscopic TiO2-based
      perovskite cells perform independently of illumination and bias conditions prior
      to the measurements, whereas the planar cells display a reversible behavior of
      illumination and applied bias-dependent I-V curves. The present study would refer
      strip road for the stability study of the perovskite solar cells. 

PMID- 25860159
TI  - Relations of vitamin D status, gender and type 2 diabetes in middle-aged
      Caucasians: teply to Dr. Guo.

PMID- 25860160
TI  - Integrative monitoring of marine and freshwater harmful algae in Washington State
      for public health protection.
AB  - The more frequent occurrence of both marine and freshwater toxic algal blooms and
      recent problems with new toxic events have increased the risk for illness and
      negatively impacted sustainable public access to safe shellfish and recreational
      waters in Washington State. Marine toxins that affect safe shellfish harvest in
      the state are the saxitoxins that cause paralytic shellfish poisoning (PSP),
      domoic acid that causes amnesic shellfish poisoning (ASP) and the first ever US
      closure in 2011 due to diarrhetic shellfish toxins that cause diarrhetic
      shellfish poisoning (DSP). Likewise, the freshwater toxins microcystins, anatoxin
      a, cylindrospermopsins, and saxitoxins have been measured in state lakes,
      although cylindrospermopsins have not yet been measured above state regulatory
      guidance levels. This increased incidence of harmful algal blooms (HABs) has
      necessitated the partnering of state regulatory programs with citizen and user
      fee sponsored monitoring efforts such as SoundToxins, the Olympic Region Harmful
      Algal Bloom (ORHAB) partnership and the state's freshwater harmful algal bloom
      passive (opportunistic) surveillance program that allow citizens to share their
      observations with scientists. Through such integrated programs that provide an
      effective interface between formalized state and federal programs and
      observations by the general public, county staff and trained citizen volunteers,
      the best possible early warning systems can be instituted for surveillance of
      known HABs, as well as for the reporting and diagnosis of unusual events that may
      impact the future health of oceans, lakes, wildlife, and humans.

PMID- 25860162
TI  - One-Pot Synthesis of 2,5-Diaryl 1,3,4-Oxadiazoles via Di-tert-butyl Peroxide
      Promoted N-Acylation of Aryl Tetrazoles with Aldehydes.
AB  - A metal- and base-free protocol for one-pot synthesis of 2,5-diaryl 1,3,4
      oxadiazoles via a radical-promoted cross-dehydrogenative coupling strategy was
      developed. This reaction involved the N-acylation of aryl tetrazoles with aryl
      aldehydes, followed by thermal rearrangement. A wide range of aryl tetrazoles and
      aryl aldehydes survived the reaction conditions to deliver the corresponding
      products in moderate to good yields. 

PMID- 25860161
TI  - Binding studies on isolated porcine small intestinal mucosa and in vitro toxicity
      studies reveal lack of effect of C. perfringens beta-toxin on the porcine
      intestinal epithelium.
AB  - Beta-toxin (CPB) is the essential virulence factor of C. perfringens type C
      causing necrotizing enteritis (NE) in different hosts. Using a pig infection
      model, we showed that CPB targets small intestinal endothelial cells. Its effect
      on the porcine intestinal epithelium, however, could not be adequately
      investigated by this approach. Using porcine neonatal jejunal explants and
      cryosections, we performed in situ binding studies with CPB. We confirmed binding
      of CPB to endothelial but could not detect binding to epithelial cells. In
      contrast, the intact epithelial layer inhibited CPB penetration into deeper
      intestinal layers. CPB failed to induce cytopathic effects in cultured polarized
      porcine intestinal epithelial cells (IPEC-J2) and primary jejunal epithelial
      cells. C. perfringens type C culture supernatants were toxic for cell cultures.
      This, however, was not inhibited by CPB neutralization. Our results show that, in
      the porcine small intestine, CPB primarily targets endothelial cells and does not
      bind to epithelial cells. An intact intestinal epithelial layer prevents CPB
      diffusion into underlying tissue and CPB alone does not cause direct damage to
      intestinal epithelial cells. Additional factors might be involved in the early
      epithelial damage which is needed for CPB diffusion towards its endothelial
      targets in the small intestine.

PMID- 25860163
TI  - 35th international symposium on intensive care and emergency medicine.

PMID- 25860164
TI  - Practical recommendations for mixing allergy immunotherapy extracts.
AB  - Critical aspects of formulating allergy immunotherapy vaccines include the
      selection, total number, and proportions of each allergen component in
      therapeutic mixtures. The immunotherapy prescription, determined by a medical
      provider, details the dosing and schedule for treatment as well as the specific
      composition of the treatment vials. Allergen extracts are composed of many
      components such as proteins, glycoproteins, and proteases. Some components in
      allergen extracts are cross-reactive, meaning that treatment with an extract from
      one species may confer partial protection against a triggering allergen from
      another species. Conversely, some allergen extracts are incompatible with other
      extracts when combined in a mixture for treatment, resulting in lowered
      therapeutic potential for the patient. Therefore, knowledge of allergen extract
      cross-reactivities and incompatibilities guides the preparation of subcutaneous
      immunotherapy prescriptions. In a clinical setting, an understanding of what can
      and can not be mixed is one critical element in improving treatment outcomes. 

PMID- 25860165
TI  - Sinus penetration of saline solution irrigation and atomizer in a cadaveric polyp
      and allergic fungal sinusitis model.
AB  - Allergic fungal sinusitis (AFS) is a stubborn disease requiring surgical and
      medical management. Delivery of topical medication is paramount in these
      patients, but the most difficult to accomplish. We investigated heavy irrigation
      (nasal douche) and atomized medication delivery potential in a cadaveric sinus
      model of polypoid AFS disease. Three disease models were created: a control that
      involved unoperated sinuses and no simulated disease; an unoperated AFS with type
      II polyposis mode; and an operated model with recurrent allergic fungal sinusitis
      with type II polyposis. The maxillary sinus showed the best irrigation and
      overall the heavy irrigator was more efficient than the atomizer. 

PMID- 25860167
TI  - A postal survey of hereditary hemorrhagic telangectasia in the northeast of
      England.
AB  - The aim of this study is to identify the demographics and epistaxis burden of
      hereditary hemorrhagic telangiectasia (HHT). A questionnaire was sent to
      participants with HHT who were recruited from a prospectively maintained
      respiratory clinic data base in a tertiary hospital. Details on demographics, HHT
      symptoms, family history, epistaxis severity, and treatment received were
      recorded. There were 34 of 60 responses (57%). Two responses were from families
      of the deceased. Of the 32 evaluable patients (men, 14; women 18), the average
      age was 51 years (range, 23-78 years). The average age of HHT diagnosis was 31
      years (range, 3-61 years). The diagnosis of HHT was made by the respiratory team
      in 13 patients; neurologist (2); ear, nose, and throat (ENT) specialist (4);
      general practitioner (5); hematologist (4); gastroenterologist (1); and not
      mentioned in two patients. Twenty-seven of 32 patients (84%) had a positive
      family history of HHT. Only 13 patients had formal genetic testing (4 endoglin, 1
      activin receptor-like kinase, 8 unknown gene). All patients who presented to the
      respiratory clinic had a background of epistaxis, which was noted on
      presentation. The average age at initial epistaxis was 14 years (range, 2-50
      years). The frequency of epistaxis was daily 63% (n = 20), weekly 9% (3), monthly
      16% (5), and a few times a year 10% (3), and unstated in one patient. Nine of 32
      patients (28%) required a transfusion. Six patients thought that they were unable
      to perform daily activities due to epistaxis. Only 15 of 32 patients (47%) were
      under the care of an ENT specialist. The treatment plan for epistaxis management
      was deemed good by 7 patients, adequate in 8, poor in 6, and not stated by 11
      patients. In conclusion, this survey is the first to quantify the epistaxis
      burden within the northeast of England. The management of epistaxis needs
      specific education and treatment to optimize the quality of life among these
      patients. 

PMID- 25860168
TI  - Monitor height ergonomics: A comparison of operating room video display
      terminals.
AB  - A surgeon's eyes should be positioned 1 meter (m) distant and no more than 15
      degrees  below the top of an operating monitor (0.27 m). We sought to determine
      which operating room video display terminal can best accommodate ergonomically
      optimized gaze during surgery. Floor to eye height was measured for surgeons in
      seated, perched, and standing positions. These ranges were then compared to
      vertical displacement ranges for monitors measured from floor to top of the
      screen. Eye height was measured for standing (1.56-1.80 m), perched (1.40-1.65
      m), and seated (1.10-1.32 m) positions. The minimum distance (min) between the
      floor and the top of the monitor and the vertical mobility range (VR) of the
      monitor were measured throughout a tertiary medical center including towers with
      boom arms (TcB) (min: 1.58 m, VR: 0.37 m), towers without booms (TsB) (min: 1.82
      m, VR: 0.025 m), ceiling mounted booms (CMB) (min: 1.34 m:, VR: 1.04 m), and
      portable monitors (PM) (min: 1.73 m, VR: 0.04 m). The tangent of 15 degrees 
      declination was used to calculate a correction factor to determine the minimum
      optimal ergonomic display height. The correction factor was subtracted from the
      eye height at each position to determine the lowest target height and the highest
      target floor to eye distance for each position. Analysis of variance with least
      significant difference post hoc testing identified all minimum distances and
      vertical ranges to be statistically different (p < 0.001). Monitor vertical
      displacement varied between styles of carts. CMB video display terminal systems
      can accommodate standing, perched and the tallest seated surgeons. TcB, TsB and
      PM systems cannot adequately accommodate all standing, perched or seated
      surgeons. 

PMID- 25860166
TI  - Endoscopic dacryocystorhinostomy as treatment for lower lacrimal pathway
      obstructions in adults: Review article.
AB  - Obstruction of the lacrimal pathway is manifested by epiphora, infection, and
      blurred vision as well as ocular and facial pain. Conservative treatments only
      achieve temporary relief of symptoms, thus surgery is the treatment of choice.
      Dacryocystorhinostomy (DCR) is recognized as the most suitable treatment for
      patients with obstructions of the lacrimal system at the level of the sac or in
      the nasolacrimal duct. The aim of this operation is to create a bypass between
      the lacrimal sac and the nasal cavity. During the past 2 decades, advances in
      rigid endoscopic equipment and other instruments have made it possible to obtain
      more information about the anatomic landmarks of the nasolacrimal system, which
      led to the development of less-invasive and safer endoscopic techniques. However,
      many parts of the treatment process related to endoscopic endonasal
      dacryocystorhinostomy (EN-DCR) still remain controversial. This article reviews
      the published literature about the technical issues associated with the success
      of EN-DCR, and clarifies the pros and cons of different pre- and postoperative
      procedures in adults with lower lacrimal pathway obstructions. 

PMID- 25860169
TI  - A retrospective study of peanut and tree nut allergy: Sensitization and
      correlations with clinical manifestations.
AB  - Peanut (PN) and tree nut (TN) allergies are among the leading causes of fatal
      food-induced anaphylaxis and are increasing in prevalence, especially in
      children. Their cosensitization and concurrent clinical allergy have been
      understudied. This retrospective study investigated the correlation between PN
      and TN allergy, both in terms of in vitro sensitization (IVS) and clinical
      allergic manifestations. We conducted a retrospective medical record review at
      the Allergy Clinic at University Hospital of Brooklyn. Fourteen hundred six
      charts were reviewed, of which 76 (5.4%) had documented relevant clinical
      allergy: PN allergy but not TN allergy (n = 29) or TN allergy but not PN allergy
      (n = 11) or both (n = 30). Six patients with PN allergy but no TN exposure
      history were not included in the analysis. The majority of patients (67/76,
      88.1%) had a concurrent history of asthma, rhinoconjunctivitis, or AD.
      Sensitivity of TN IVS predicting PN IVS was 38/39 (97%). Similarly, sensitivity
      of PN IVS predicting TN IVS was 38/42 (91%). Sensitivity of TN clinical allergy
      predicting PN allergy was 30/59 (51%). Sensitivity of PN clinical allergy
      predicting TN allergy was 30/41 (73%). The total number of organ systems involved
      in reported clinical reactions correlated with IVS to TN (p = 0.004) but not IVS
      to PN (p = 0.983). In summary, we found PN sensitization predicts TN
      sensitization in vitro, with lower predictability for clinical reactions. 

PMID- 25860170
TI  - Chronic vulvovaginal Candida hypersensitivity: An underrecognized and
      undertreated disorder by allergists.
AB  - Vulvovaginal candidiasis infections are estimated to occur at least once during
      the lifetime of 75% of the female population. It has been proposed that some
      women with recurrent vulvovaginal candidiasis (RVVC) develop sensitization to
      Candida albicans and clinically improve in response to Candida immunotherapy.
      Here, we report a case series of 12 women diagnosed with chronic vulvovaginal
      Candida hypersensitivity subsequently treated with Candida immunotherapy and
      review potential systemic and localized host immune defense mechanisms involved
      in C. albicans overgrowth and sensitization. A retrospective review of
      vulvovaginal Candida hypersensitivity in women who were treated with C. albicans
      immunotherapy over the past eight years was conducted. Twelve women who qualified
      for a diagnosis of vulvovaginal Candida hypersensitivity were treated with
      Candida immunotherapy. Eleven of the 12 (92%) women reported clinical improvement
      after immunotherapy. The majority of these women were not sensitized to seasonal
      or perennial aeroallergens and clinically responded to lower concentrations of C.
      albicans allergen than what has been previously reported. In general, Candida
      immunotherapy was well tolerated. Chronic vulvovaginal Candida hypersensitivity
      is an underrecognized disorder by primary care physicians and therefore an
      undertreated disorder by allergists. A double-blinded, placebo-controlled
      randomized trial is necessary to firmly establish the efficacy of treatment with
      Candida immunotherapy. This investigation should be designed to include
      mechanistic studies that would help to better understand the etiology of this
      disorder. 

PMID- 25860171
TI  - Perioperative management for patients with hereditary angioedema.
AB  - Hereditary angioedema (HAE) is a rare autosomal dominant disease that results
      from mutations in the C1-esterase inhibitor (C1-INH) gene. HAE is characterized
      by recurrent episodes of angioedema of the skin (face, extremities, genitalia,
      trunk), the gastrointestinal tract, and respiratory tract. Symptoms experienced
      can be debilitating, may impact quality of life, and can be life threatening.
      Preventing attacks particularly for patients undergoing procedures is critical.
      Patients with HAE may now treat acute attacks or prevent attacks with medications
      that have recently become available in the United States; however, these same
      medications can be used for perioperative management for patients undergoing
      medical, surgical, and dental procedures. Periprocedural planning is important
      for patients to reduce the incidence of acute attacks. Education is critical and
      increasing awareness of short-term prophylaxis options will allow providers to
      develop an appropriate action plan for their patients. The goal of this review is
      to increase awareness for HAE treating physicians, surgeons, anesthesia, and
      emergency room physicians by examining the available treatment options,
      researching the literature, and summarizing available data for periprocedural
      management. The availability of treatment options has increased over the past few
      years, expanding options for physicians and patients living with HAE and improve
      safety during the perioperative period and at the time of other procedures. 

PMID- 25860172
TI  - Characterization of stacked-crystal PET detector designs for measurement of both
      TOF and DOI.
AB  - A PET detector with good timing resolution and two-level depth-of-interaction
      (DOI) discrimination can be constructed using a single-ended readout of
      scintillator stacks of Lanthanum Bromide (LaBr3), with various Cerium dopant
      concentrations, including pure Cerium Bromide (CeBr3). The stacked crystal
      geometry creates a unique signal shape for interactions occurring in each layer,
      which can be used to identify the DOI, while retaining the inherently good timing
      properties of LaBr3 and CeBr3. In this work, single pixel elements are used to
      optimize the choice of scintillator, coupling of layers, and type of
      photodetector, evaluating the performance using a fast, single-channel
      photomultiplier tube (PMT) and a single 4 * 4 mm(2) silicon photomultiplier
      (SiPM). We also introduce a method to quantify and evaluate the DOI
      discrimination accuracy. From signal shape measurements using fast waveform
      sampling, we found that in addition to differences in signal rise times, between
      crystal layers, there were also differences in the signal fall times. A DOI
      accuracy of 98% was achieved using our classification method for a stacked
      crystal pair, consisting of a 15 mm long LaBr3(Ce:20%) crystal on top of a 15 mm
      long CeBr3 crystal, readout using a PMT. A DOI accuracy of 95% was measured with
      a stack of two, identical, 12 mm long, CeBr3 crystals. The DOI accuracy of this
      crystal pair was reduced to 91% when using a SiPM for readout. For the stack of
      two, 12 mm long, CeBr3 crystals, a coincidence timing resolution (average of
      timing results from the top and bottom layer) of 199 ps was measured using a PMT,
      and this was improved to 153 ps when using a SiPM. These results show that with
      stacked LaBr3/CeBr3 scintillators and fast waveform sampling nearly perfect DOI
      accuracy can be achieved with excellent timing resolution-timing resolution that
      is only minimally degraded compared to results from a single CeBr3 crystal of
      comparable length to the stacked crystals. The interface in the stacked crystal
      geometry itself plays a major role in creating the differences in signal shape
      and this can be used to construct stacked DOI detectors using the same
      scintillator type, thereby simplifying and broadening the application of this
      technique. 

PMID- 25860173
TI  - Contribution of Ninjurin1 to Toll-like receptor 4 signaling and systemic
      inflammation.
AB  - Nerve injury-induced protein (Ninjurin [Ninj]) 1 is an adhesion molecule
      originally identified in Schwann cells after nerve injury, whereas it is also
      expressed in leukocytes, epithelium, endothelium, and various organs, and is
      induced under inflammatory conditions. Its contribution to inflammation was so
      far restricted to the nervous system and exclusively attributed to its role
      during leukocyte migration. We hypothesized a proinflammatory role for Ninj1 also
      outside the nervous system. To elucidate its impact during inflammation, we
      analyzed expression levels and its contribution to inflammation in septic mice
      and studied its effect on inflammatory signaling in vitro. The effect on
      inflammation was analyzed by genetic (only in vitro) and pharmacologic repression
      in septic mice (cecal ligation and puncture) and cell culture, respectively.
      Repression of Ninj1 by an inhibitory peptide or small interfering RNA attenuated
      LPS-triggered inflammation in macrophages and endothelial cells by modulating p38
      phosphorylation and activator protein-1 activation. Inhibition of Ninj1 in septic
      mice reduced systemic and pulmonary inflammation as well as organ damage, and
      ameliorated survival after 24 hours. Ninj1 is elevated under inflammatory
      conditions and contributes to inflammation not only by mediating leukocyte
      migration, but also by modulating Toll-like receptor 4-dependent expression of
      inflammatory mediators. We assume that, owing to both mechanisms, inhibition
      reduces systemic inflammation and organ damage in septic mice. Our data
      contribute to a better understanding of the complex inflammatory mechanisms and
      add a novel therapeutic target for inflammatory conditions such as sepsis. 

PMID- 25860175
TI  - Editorial: in silico drug design and medicinal chemistry).
AB  - Medicinal chemistry is not limited to molecules, their structures and design but
      also highly cohesive to pharmacological activities. The potency of a molecule
      varies by its structure. Hence structural activity relationship is the sub-branch
      which deals with the estimation of ability of a molecule in depicting any
      pharmacological activity. In silico drug design is a novel technique which is
      employed in designing a molecule by using computer aided software's and bringing
      a superior and potent molecule. In recent years, in silico drug design has been
      merged with medicinal chemistry especially by the techniques like ligand based
      strategy to isolate the required structures. By such strategic techniques, there
      are high chances of delivering high throughput screening which involves of
      screening large number of molecules in a very less time. Involvement of such
      techniques would be a boon for development of new drug entity as it can aid in
      development of newer, safe, effective and potent drug molecules. Hence, the
      present issue is aimed to emphasize the cohesion between in silico drug design
      and it significance in medicinal chemistry. The articles which would be published
      will mainly focus on the role of in silico drug design techniques in the
      development of molecules to target various disease and disorders. Molecules can
      from natural/ synthetic/semi synthetic origin. Articles will be a treasure box
      consisting of employment of computational methods for unprecedented molecules.
      The issue will be sure an endorsement for international readership and
      researchers.

PMID- 25860174
TI  - Alyssum homolocarpum seeds: phytochemical analysis and effects of the seed oil on
      neural stem cell proliferation and differentiation.
AB  - Pharmacognostic evaluation of medicinal plants may assess their current
      applications and possibly results in finding new active components. In this
      study, ash and extractive values and high performance thin layer chromatography
      fingerprints of Alyssum homolocarpum (Brassicaceae) seed extracts were
      investigated to elucidate its composition. Differential scanning calorimetry and
      gas chromatography-mass spectrometry analysis were employed to determine the
      components of A. homolocarpum seed oil (AHO). Neurosphere assay, in vitro
      differentiation and immunofluorescence analysis were performed to evaluate the
      effects of oral administration of AHO (0.5 or 1 g/kg/day for 14 days) on
      proliferation and differentiation of neural stem cells (NSCs) in adult male
      BALB/c mice. Total, acid-insoluble and water-soluble ash values were determined
      as 45.83 +/- 5.85, 6.67 +/- 2.89 and 28.33 +/- 2.89 mg/g, respectively. The
      extractive values were 4.90, 0.43 and 0.56 % (w/w) for n-hexane, dichloromethane
      and ethanolic extracts, respectively. Interestingly, AHO was mainly composed of
      alpha-linolenic acid (89.71 %), beta-sitosterol (3.3 mg/g) and campesterol (0.86
      mg/g). Administration of AHO at 1 g/kg/day significantly increased proliferation
      of NSCs, as evidenced by an increase in mean neurosphere-forming frequency per
      brain (872.7 +/- 15.17) and neurosphere diameter (101 +/- 2.48 um) compared to
      the control group (424.3 +/- 59.29 and 78.63 +/- 1.7 um, respectively; P < 0.05).
      AHO treatment did not affect in vitro differentiation of the harvested NSCs. Our
      data show that A. homolocarpum seed oil is a rich source of alpha-linolenic acid
      and beta-sitosterol with potential therapeutic application to enhance NSC
      proliferation and recruitment in neurological diseases. 

PMID- 25860176
TI  - Molecular modeling based synthesis and evaluation of in vitro anticancer activity
      of indolyl chalcones.
AB  - A series of twenty one chalcone derivatives having indole moiety were synthesized
      and were evaluated against four human cancer cell lines. Indolyl chalcones 1a,
      1b, 1d, 1f-1j, 2c, 2e, 2i showed good anticancer activity. Chalcones 1b and 1d
      were the most active and selective anticancer agents with IC50 values <1MUg/ml
      and 1.51MUg/ml, against WRL-68 cell line, respectively. Molecular mechanism was
      explored through in silico docking & ADMET studies. 

PMID- 25860177
TI  - Synthesis, antimicrobial, anticancer evaluation and QSAR studies of 3/4-bromo
      benzohydrazide derivatives.
AB  - A series 3/4-bromo-N'-(substituted benzylidene/furan-2-ylmethylene/5
      oxopentylidene/3- phenylallylidene)benzohydrazides (1-23) was synthesized and
      characterized by physicochemical and spectral means. The synthesized compounds
      were screened for their antimicrobial and anticancer potentials. Antimicrobial
      activity results indicated that compound 12 (pMICam = 1.67 MUM/ml) was the most
      potent antimicrobial agent. The synthesized benzohydrazides were also having good
      anticancer potential and compound 22 (IC50 = 1.20 MUM MUM) was found to be the
      most potent anticancer agent which was more potent than standard drugs,
      tetrandrine (IC50 = 1.53) and 5- fluorouracil (IC50 = 4.6 MUM). QSAR studies
      indicated that antimicrobial activity of synthesized compounds was best described
      by electronic parameter, total energy (Te) and topological parameters, valance
      zero order molecular connectivity index ((0)chi(v)) and Wiener index (W). 

PMID- 25860178
TI  - Enantioselective Synthesis of the ABC-Tricyclic Core of Phomactin A by a gamma
      Hydroxylation Strategy.
AB  - An enantioselective synthesis of the ABC-tricyclic furanochroman core of
      phomactin A has been accomplished by a gamma-hydroxylation approach. The C ring
      was established by gamma-hydroxylation of an alpha-enone. The regioselectivity
      was optimized by using a strong base with an oxophilic cation (t-BuLi) and a
      bulky oxygen donor (Davis reagent), which afforded the gamma-hydroxylation
      product selectively in 63% yield. 

PMID- 25860179
TI  - Challenges in the interpretation of protein h/d exchange data: a molecular
      dynamics simulation perspective.
AB  - Many protein structural investigations involve the use of H/D exchange (HDX)
      techniques. It is commonly thought that amide backbone protection arises from
      intramolecular H-bonding and/or burial of NH sites. Recently, fundamental HDX
      related tenets have been called into question. The current work focuses on
      ubiquitin for exploring the defining features that distinguish amides in "open"
      (exchange-competent) and "closed" (exchange-incompetent) environments. Instead of
      relying on static X-ray structures, we employ all-atom molecular dynamics (MD)
      simulations for obtaining a dynamic view of the protein ground state and its
      surrounding solvent. The HDX properties for 57 out of 72 NH sites can be readily
      explained on the basis of backbone and side chain H-bonding, as well as solvent
      accessibility considerations. Unexpectedly, the same criteria fail for predicting
      the HDX characteristics of the remaining 15 amides. Significant protection is
      seen for numerous exposed NH sites that are not engaged in intramolecular H
      bonds, whereas other amides that seemingly share the same features are
      unprotected. We scrutinize the proposal that H-bonding to crystallographically
      defined water can cause the protection of surface amides. For ubiquitin, the
      positioning of crystal water is not compatible with this idea. To further explore
      possible solvation effects, we tested for the presence of partially immobilized
      water networks. Our MD data reveal no difference in the solvation properties of
      protected vs unprotected surface amides, making it unlikely that restricted water
      dynamics can cause anomalous amide protection. The findings reported here suggest
      that efforts to deduce protein structural features on the basis of HDX protection
      factors may yield misleading results. This conclusion is relevant for initiatives
      that rely on sparse structural data as constraints for elucidating protein
      conformations. It may be necessary to pursue detailed quantum mechanical studies
      of the protein, the solvent, and the hydroxide catalyst for obtaining a
      comprehensive understanding of the factors that govern HDX rates. The
      considerable size of the systems involved makes such endeavors a daunting task. 

PMID- 25860180
TI  - Malicious MXit? South African adolescents' use of mobile-based communication
      applications.
AB  - Across the globe, and particularly in the high-income countries of the developed
      world, adolescents are resorting in increasing numbers to the virtual world for
      peer interaction and socialisation (Subrahmanyam, Smahel and Greenfield 2006).
      This new and popular way of relating through virtual mediums such as the Internet
      has sparked public concern, and has been a focus of academic debate. Ongoing
      debate in psychology literature discusses the notion of compulsive usage of
      online communication platforms (commonly termed Internet addiction), particularly
      among adolescents (Kim et al. 2006, Fu et al. 2010, Israelashvili, Kim and
      Bukobza 2012). 

PMID- 25860181
TI  - Exploring foundation phase school teachers' perceptions of learning difficulties
      in two Johannesburg schools.
AB  - OBJECTIVES: According to the 2001 census (StatsSA 2001), approximately 12% of the
      population in South Africa are intellectually disabled and 7% of the population
      have a communication disability. Early diagnosis and intervention is vital for
      optimum functioning in later life yet most children are not identified until well
      into their schooling. Since foundation phase teachers are amongst the first to
      encounter these difficulties, this research explored foundation phase teachers'
      perceptions of learners with learning difficulties (LD) in two inner city public
      schools in Johannesburg. METHODS: Eight teachers were interviewed using a semi
      structured interview schedule. The challenges associated with dealing with
      children who have a LD together with issues of stigma and parents responses were
      explored. Thematic content analysis was used to analyse the results. RESULTS:
      Seven themes were identified, namely understanding of LD, symptoms of LD,
      aetiology of LD, impact LD has on a learner, stigmatisation of learners with LD,
      parental denial and inclusive education. CONCLUSION: From the results, it was
      evident that LD needs a more contextually appropriate definition in South Africa
      for teachers to correctly identify these learners. Furthermore, teachers require
      more training for them to effectively cope with learners with LD.

PMID- 25860182
TI  - Child and adolescent mental health in South Africa.
AB  - Mental health problems in childhood and adolescence pose a major threat to public
      health. Epidemiological studies in high, middle and low income countries indicate
      that approximately one in five children and adolescents suffer from a mental
      disorder. In many instances these persist into adulthood. In South Africa, HIV
      infection, substance use, and exposure to violence increase vulnerability to
      mental disorders. Child and adolescent mental health services play a key role in
      reducing the burden of mental disorders in childhood and later in adulthood. This
      paper focuses on service needs for children and adolescents in South Africa. It
      commences with a discussion of the prevalence of child and adolescent psychiatric
      disorders after which the legal and policy context of child and adolescent
      psychiatric services is described. A framework for child and adolescent mental
      health service provision is presented, following which steps for reducing the
      extent of unmet service need are considered. The paper concludes with a call to
      scale up child and adolescent mental health services in South Africa, based on
      the stark realities of unmet need and the constitutional rights of children and
      adolescents to appropriate mental health care. 

PMID- 25860183
TI  - Level of depression among adolescents of religious minorities and their dominant
      counterparts in Pakistan.
AB  - OBJECTIVE: This study investigated the level of depression among religious
      minority adolescents (Christians and Hindus) in comparison with their dominant
      counterparts (Muslims) in Pakistan. For this purpose, based on literature
      available, we hypothesised that adolescents of religious minorities would have a
      higher level of depression than their dominant counterparts. DESIGN: Between
      group design was used as it was considered most appropriate for this study where
      a religious minority adolescent group was compared with its dominant counterpart.
      METHOD: A total of 320 adolescents participated in this study of whom 160
      belonged to the minority religious groups (i.e. 76 Christians and 84 Hindus) and
      160 to the dominant religious group, i.e. Muslims. To assess the level of
      depression in the participants, Reynolds Adolescents Depression Scale (2nd ed.,
      Reynolds 2002) was used. RESULTS: One-Way Analysis of Variance was used to
      analyse the data in statistical terms to reveal any significant difference or
      differences between these two groups. CONCLUSIONS: The findings of the study
      suggest that religious minority adolescents (Christians and Hindus) in Pakistan
      are inclined to have higher levels of depression than their dominant counterparts
      (Muslim adolescents).

PMID- 25860184
TI  - Zero degrees of empathy: A new theory of human cruelty.

PMID- 25860185
TI  - Journal abstracts from current research in the field of child and adolescent
      mental health.

PMID- 25860186
TI  - Intellectually disabled child and adolescent sexual violence survivors face
      greater challenges in the legal system.

PMID- 25860188
TI  - Older people living with HIV in Uganda: understanding their experience and needs.
AB  - Older adults ageing with HIV in Africa have been largely neglected, despite the
      distinctive healthcare needs of this population. This article examines the
      medical care experiences of older Ugandans living with HIV. Data were collected
      from 40 HIV-positive adults, aged 50 years or older, attending two clinics in
      Uganda. Individual in-depth interviews were conducted with 16 adults and four
      focus groups were conducted with a total of 24 adults. Observations of clinic
      interactions were also recorded. Mean age of the participants was 65 years (range
      50 to 80 years), and 50% were females. Interview transcripts were analysed using
      thematic content analysis. Although most issues raised were not qualitatively
      different for older individuals versus younger ones, from the analysis, nine
      major themes emerged, revealing healthcare needs distinctive to older people
      living with HIV: 1) stigma (43%); 2) difficulty disclosing (8%); 3) delayed
      diagnosis and care-seeking (55%); 4) access to care (80%); 5) quality of patient
      provider relationship (75%); 6) adherence support (25%); 7) serodiscordance
      (20%); 8) continuity of care (14%); and, 9) end-of-life issues (13%) and other
      issues (20%). Most participants attributed a double burden of stigma - from HIV
      and old age - as a major factor affecting access to healthcare for HIV. Most of
      the participants expressed anxiety about securing healthcare in the future and
      concern about the lack of social services. Many participants had problems with
      transportation and food that compromised their adherence to antiretroviral
      therapy. HIV-prevention, treatment and care programmes should seek to meet the
      special needs of older people through focused and innovative approaches. Further
      research with larger samples is needed to explore the impact of these healthcare
      needs on the quality of life of older people living with HIV. 

PMID- 25860187
TI  - New Insights into Low-Temperature Oxidation of Propane from Synchrotron
      Photoionization Mass Spectrometry and Multiscale Informatics Modeling.
AB  - Low-temperature propane oxidation was studied at P = 4 Torr and T = 530, 600, and
      670 K by time-resolved multiplexed photoionization mass spectrometry (MPIMS),
      which probes the reactants, intermediates, and products with isomeric selectivity
      using tunable synchrotron vacuum UV ionizing radiation. The oxidation is
      initiated by pulsed laser photolysis of oxalyl chloride, (COCl)2, at 248 nm,
      which rapidly generates a ~1:1 mixture of 1-propyl (n-propyl) and 2-propyl (i
      propyl) radicals via the fast Cl + propane reaction. At all three temperatures,
      the major stable product species is propene, formed in the propyl + O2 reactions
      by direct HO2 elimination from both n- and i-propyl peroxy radicals. The
      experimentally derived propene yields relative to the initial concentration of Cl
      atoms are (20 +/- 4)% at 530 K, (55 +/- 11)% at 600 K, and (86 +/- 17)% at 670 K
      at a reaction time of 20 ms. The lower yield of propene at low temperature
      reflects substantial formation of propyl peroxy radicals, which do not completely
      decompose on the experimental time scale. In addition, C3H6O isomers
      methyloxirane, oxetane, acetone, and propanal are detected as minor products. Our
      measured yields of oxetane and methyloxirane, which are coproducts of OH
      radicals, suggest a revision of the OH formation pathways in models of low
      temperature propane oxidation. The experimental results are modeled and
      interpreted using a multiscale informatics approach, presented in detail in a
      separate publication (Burke, M. P.; Goldsmith, C. F.; Klippenstein, S. J.; Welz,
      O.; Huang H.; Antonov I. O.; Savee J. D.; Osborn D. L.; Zador, J.; Taatjes, C.
      A.; Sheps, L. Multiscale Informatics for Low-Temperature Propane Oxidation:
      Further Complexities in Studies of Complex Reactions. J. Phys. Chem A. 2015, DOI:
      10.1021/acs.jpca.5b01003). The model predicts the time profiles and yields of the
      experimentally observed primary products well, and shows satisfactory agreement
      for products formed mostly via secondary radical-radical reactions. 

PMID- 25860189
TI  - Poverty, sexual behaviour, gender and HIV infection among young black men and
      women in Cape Town, South Africa.
AB  - This article contributes methodologically and substantively to the debate over
      the importance of poverty, sexual behaviour and circumcision in relation to HIV
      infection, using panel data on young black men and women in Cape Town, South
      Africa. Methodological challenges included problems of endogeneity and blunt
      indicator variables, especially for the measurement of sexual behaviour. Noting
      these difficulties, we found that the importance of socioeconomic and sexual
      behavioural factors differed between men and women. While we found a clear
      association between the number of years of sexual activity and HIV status among
      both men and women, we found that past participation in a concurrent sexual
      partnership increased the odds of HIV infection for men but not women. Women, but
      not men, who made the transition from school to tertiary education (our key
      indicator of socioeconomic status) were less likely to be HIV-positive than those
      who made the transition from school to unemployment. Both poverty and sexual
      behaviour matter to individuals' HIV risk, but in gendered ways. 

PMID- 25860190
TI  - 'Trophy-hunting scripts' among male university students in Zimbabwe.
AB  - Drawing on a multi-method qualitative study, this article examines 'trophy
      hunting' scripts among male university students in Zimbabwe. 'Trophy hunting' is
      a term I have adopted to refer to hegemonic masculinity rituals through which men
      gain social admiration for dating and having sex with as many women as possible.
      I argue that this trophy hunting is exacerbated by the 'crisis of masculinity'
      which has been brought about by the harsh macroeconomic environment in Zimbabwe.
      The latter has reduced men's access to the material trappings that denote
      successful masculinity in a competitive and materialistic environment. Sexual
      scripting that is based on such trophy hunting makes students susceptible to
      acquiring HIV infection. Research was conducted with 69 male social-science
      students at a Zimbabwean university, and the findings were analysed within a post
      structural conceptual framework. The findings point to the existence of 'toxic
      masculinities' among male students. In their endeavour to live up to hegemonic
      masculinity expectations of the university bachelor, they end up being trapped in
      what can be described as 'toxic masculinity entrapments.' There is a need to
      challenge these identities if efforts against HIV and AIDS are to be successful. 

PMID- 25860192
TI  - Correlates of HIV-status awareness among adults in Nairobi slum areas.
AB  - The prevalence of HIV in the adult population in slum areas in Nairobi, Kenya, is
      higher than for residents in the city as a whole. This disparity suggests that
      the characteristics of slum areas may adversely influence the HIV-prevention
      strategies directed at reducing the national prevalence of HIV. The objective of
      the study was to identify some of the sociodemographic and behavioural correlates
      of HIV-status awareness among the adult population of two slums in Nairobi. In a
      household-based survey conducted by the African Population and Health Research
      Center (APHRC), 4 767 men and women aged between 15 and 54 years were randomly
      sampled from two slums (Korogocho and Viwandani) in Nairobi and data were
      collected on the social and health context of HIV and AIDS in these settlements.
      Bivariate and multivariate logistic regression analyses were conducted to
      identify factors associated with HIV-status awareness. The proportion of
      respondents that had ever been tested and knew their HIV status was 53%, with the
      women having greater awareness of their HIV status (62%) than the men (38%).
      Awareness of HIV status was significantly associated with age, sex, level of
      education, marital status and slum of residence. The lower level of HIV-status
      awareness among the men compared with the women in the slums suggests a poor
      uptake of HIV-testing services by males. Innovative strategies are needed to
      ensure greater access and uptake of HIV-testing services by the younger and less
      educated residents of these slums if the barriers to HIV-status awareness are to
      be overcome. 

PMID- 25860191
TI  - Poor-quality health services and lack of programme support leads to low uptake of
      HIV testing in rural Mozambique.
AB  - Mozambique has one of the world's highest burdens of HIV infection. Despite the
      increase in HIV-testing services throughout the country, the uptake has been low.
      To identify barriers to HIV testing we conducted a study in six rural districts
      in Zambezia Province. We recruited a total of 124 men and women from the
      community through purposeful sampling to participate in gender-specific focus
      group discussions about barriers to HIV testing. The participants noted three
      main barriers to HIV testing: 1) poor conduct by clinicians, including
      intentional disclosure of patients' HIV status to other community members; 2)
      unintentional disclosure of patients' HIV status through clinical practices; and,
      3) a widespread fatalistic belief that HIV infection will result in death,
      particularly given poor access to adequate food. Improving quality and
      confidentiality within clinical service delivery, coupled with the introduction
      of food-supplement programmes should increase people's willingness to test and
      remain in care for HIV disease. 

PMID- 25860193
TI  - Perceptions of educators of Deaf and hard-of-hearing adolescents of HIV-risk
      factors for these youths.
AB  - Like the general population in South Africa, adolescents with deafness or who are
      hard-of-hearing may be vulnerable to HIV infection. They are exposed to all known
      risk factors for HIV infection. Educators who work in schools for Deaf (meaning
      culturally deaf) and hard-of-hearing adolescents can provide valuable information
      about HIV-risk factors for these youths. We conducted 21 in-depth interviews and
      two focus group discussions with educators of Deaf and hard-of-hearing
      adolescents in six schools in two provinces of South Africa. We explored the
      participants' perceptions of the HIV-risk factors to which their learners are
      exposed. The educators were aware of the adolescents' vulnerability to HIV
      infection. All the participants believed that Deaf and hard-of-hearing
      adolescents are at risk of contracting HIV due to vulnerability to sexual abuse
      and higher-risk sexual behaviour. The participants were aware of substance abuse
      patterns, such as excessive alcohol use or recreational drug use, among their
      learners. Adolescence is a vulnerable period, and adolescents who are Deaf or
      hard-of-hearing are likewise exposed to the risk of HIV infection. 

PMID- 25860194
TI  - HIV-seroprevalence among pulmonary tuberculosis patients in a tertiary care
      hospital in Douala, Cameroon.
AB  - A retrospective study was carried out at Douala General Hospital, Cameroon,
      between July 2007 and July 2011, to determine the prevalence of HIV infection
      among the pulmonary tuberculosis (pTB) patients and to compare epidemiological
      profiles with respect to TB/HIV co-infection. The cases of all patients aged 15
      years and above and diagnosed with pTB during the study period were reviewed.
      Sociodemographic data, sputum examination for acid-fast bacilli, previous TB
      treatment status, and HIV status were recorded. The chi-square or Fisher's exact
      tests were used to compare the proportions. The independent sample t-test was
      used to compare means for the quantitative data. Of the 383 pTB patients
      included, 56.1% were males. The mean age was 38.9 +/- 13.9 years (range 15-95).
      The age group 25-44 years was most represented, with 55.6% of the patients, while
      the least represented age group was that of patients over 65 years. The mean age
      of the females (36.2 +/- 13.6 years) was statistically lower than that of the
      males (41.1 +/- 13.8 years). Smear-positive pTB was diagnosed in 208 cases
      (54.6%). All the patients were tested for HIV infection. The overall prevalence
      of HIV among the pTB patients was 50.4%. There were no significant differences
      between the HIV-positive and HIV-negative groups with respect to age, sex, sputum
      examination for acid-fast bacilli, and previous TB-treatment status. The results
      suggest that the TB/HIV co-infection rate in Cameroon is high. Intensification of
      the screening of HIV infection in the general population and early management of
      HIV disease, especially in young women, could reduce the incidence of TB. 

PMID- 25860195
TI  - An exploratory study of the individual determinants of students' sexual risk
      behaviour at a South African university.
AB  - The prevalence of sexual risk behaviour is high on campuses at South African
      universities, putting many students at risk of HIV infection. This study explores
      individual influences on students' sexual risk-taking behaviour at the University
      of KwaZulu-Natal. The study collected cross-sectional data obtained between late
      2008 and early 2010. A total of 80 in-depth interviews and four focus group
      discussions were conducted, allowing for an equal representation of males and
      females and a mix of different races (black, white, Indian and coloured) among
      students at two campuses (Howard College and Pietermaritzburg) and at different
      levels of study (undergraduate and postgraduate). The data were analysed using
      thematic analysis to identify factors associated with the students' sexual risk
      behaviour. Sexual risk behaviour was found to be influenced by a range of
      individual factors, especially: personal beliefs about long-term relationships;
      attitudes towards sex for variety; a drive for material wealth; a lack of
      satisfaction in relationships; levels of trust and attention; pursuit of the long
      term goal of marriage; and HIV denialism. As young adults, university students
      lack experience in assessing influences on their risk-taking behaviour, thus they
      require education on the individual risk factors that put them at risk of
      acquiring HIV infection. Likewise, the nature of these factors pose significant
      challenges to reducing sexual risk behaviour among university students. 

PMID- 25860196
TI  - Media ownership and news framing: an analysis of HIV/AIDS coverage by Ugandan
      press.
AB  - Applying framing theory, the present research analyzes trends in Ugandan news
      coverage and the prominent issue frames for HIV/AIDS-related stories. In order to
      determine the influence of other factors, such as media ownership and journalist
      origin, nearly 800 articles, from 2000 to 2004, were gathered from the major
      private newspaper and government-owned newspaper in Uganda. After systematic
      sampling, 365 articles constitute the sample. The results indicate that print
      news coverage of HIV and AIDS followed a non-linear trajectory, declining from
      2000-2002 and then increasing from 2003-2004. Curative medicine emerged as the
      most prominent issue frame. Higher-risk behaviour was the least prominent issue
      frame overall. The 'solutions' issue frame nearly doubled in prominence from 2000
      2004, while the HIV-prevention frame decreased from 2000-2002 and then rebounded
      from 2003-2004. Concerning HIV-related topics, the private newspaper included
      more features, printed lengthier articles, incorporated a greater variety of news
      frames, and published more articles by foreign journalists than the government
      owned newspaper. The private newspaper employed the 'HIV-prevention,' 'action,'
      and 'victims' frames more often than the government-owned newspaper. Journalists
      at the government-owned newspaper adopted a 'solutions' frame more often than
      their private-press counterparts. Though foreign journalists were more likely
      than local journalists to employ the HIV-prevention frame, additional tests
      revealed that the news organisation for which the journalists worked contributed
      to issue framing to a greater extent than did either a local or foreign reporting
      origin. Local (Ugandan) journalists working for the two news organisations
      differed in their tendencies to apply the HIV-prevention, action, victims, and
      tragedy frames in news stories on HIV and AIDS, with journalists at the private
      newspaper using these frames more often than did journalists at the government
      owned newspaper. 

PMID- 25860197
TI  - [The problem with the hammer].

PMID- 25860198
TI  - [Bisphosphonate-associated osteonecrosis of the jaw].
AB  - BACKGROUND: Bisphosphonates (BP) are used in the treatment of severe osteoporosis
      and metastasis of malignant diseases. A possible relationship between the
      occurrence of osteonecrosis of the jaw and BP therapy was first described in
      2003. Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is difficult to
      treat. In some cases the condition of the patients is so compromised that only
      minimally invasive surgery is possible. Histopathologically, osteonecrosis shows
      the features of chronic sequestered osteomyelitis, which can be found in
      different areas of the upper and lower jaw. Sometimes extensive resections of the
      jaw are necessary. Thus, BRONJ can cause mutilation, impairment of function and
      esthetics in the orofacial system and, thereby, compromise the life quality of
      the patients. Triggering factors are often tooth extraction without surgical
      plastic wound closure of the alveoli, but can also be associated with bruises
      from denture or other minor wounds. OBJECTIVES: The purpose of this article is to
      present results from our own patient collective, including therapy regime,
      success rate, and therapy recommendations. METHODS: The patient populations at
      three German hospitals were analyzed using a standard questionnaire. The patients
      in the study group, entered into a follow-up system for early detection of
      possible BRONJ, were evaluated for treatement outcome. RESULTS: The success rate
      for prophylactic surgery in asymptomatic patients was very high at 96 %. In the
      group with symptomatic BRONJ, the outcome was significantly lower (76.4 %).
      CONCLUSIONS: Because of the complex symptoms, close cooperation between
      oncologists, dentists, and maxillofacial surgeons is required in the treatment of
      BRONJ. Before starting therapy with bisphosphonates and during the therapy,
      dental treatment and monitoring of the patient' oral health is necessary.

PMID- 25860199
TI  - [Direct inhibition of TRPV1 by acetylsalicylic acid : New effect of an old drug].

PMID- 25860200
TI  - [Serotonin syndrome and pain medication : What is relevant for practice?].
AB  - Serotonin syndrome is a dangerous and rare complication of a pharmacotherapy and
      can lead to death. Caused by unwanted interactions of serotonergic drugs, it is
      characterised by a neuroexcitatory triad of mental changes, neuromuscular
      hyperactivity and autonomic instability. Opioids with serotonergic effects
      include the phenylpiperidine series opioids fentanyl, methadone, meperidine and
      tramadol and the morphine analogues oxycodone and codeine. In combination with
      certain serotonergic drugs, e.g. antidepressants, they can provoke serotonin
      syndrome. In patients with such combinations, special attention should be paid to
      clinical signs of serotonergic hyperactivity. Higher risk combinations (e.g.
      monoamine oxidase inhibitors with tramadol) must be avoided. Treatment with
      serotonergic agents must be stopped in moderate or severe serotonin syndrome.
      Patients with a severe serotonin syndrome require symptomatic intensive care and
      specifically a pharmacological antagonism with cyproheptadine or chlorpromazine. 

PMID- 25860201
TI  - Missed Central Venous Guide Wires: A Systematic Analysis of Published Case
      Reports.
AB  - OBJECTIVE: The inadvertent loss of an entire guide wire during central venous
      catheterization can lead to serious patient harm and require additional
      investigations as well as retrieval procedures. We aimed to analyze globally
      published reports of lost wires during central venous catheterization to
      understand its possible etiology, presentation, treatment, and outcomes with an
      objective of finding solutions to make the procedure safer. DATA SOURCES:
      MEDLINE, Scopus, and CINAHL, supplemented by scanning the reference lists of
      relevant publications. STUDY SELECTION: All reports describing an inadvertent
      intravascular loss of a complete guide wire during placement of central venous
      catheters published up to December 2014 were included. Reports exclusively
      describing the 1) retrieval method, 2) partially retained guide wires, and 3)
      entrapped guide wires during withdrawal were excluded. DATA EXTRACTION: In each
      instance, we collected data about the method of the missed guide wire detection,
      the time interval between the procedure and detection, the supplementary
      investigations performed to confirm the diagnosis, and the risk factors
      associated with such events as well as the complications, the final outcome, and
      the wire retrieval methods used. DATA SYNTHESIS: A systematic analysis of the
      accessed publications was performed. CONCLUSIONS: Over the last decade, the
      number of reported instances of lost guide wires during central venous
      catheterization has increased rapidly. Unsupervised or improperly supervised
      insertions of the central catheters by trainees, distractions during insertions,
      and high workload are the main risk factors. A retained guide wire increases the
      risk and cost of additional diagnostic and therapeutic interventions, as well as
      imposing many minor-to-serious life-threatening complications. Continuing
      education along with simulator-based skill development, vigilant supervision, and
      a shared workload during out of hours working are likely to prevent such
      occurrences.

PMID- 25860202
TI  - Transfusion of Old RBCs Induces Neuroinflammation and Cognitive Impairment.
AB  - OBJECTIVES: Transfusing RBCs stored for longer than 14 days (old RBC) in humans
      is common. This transfusion can injure organs, such as lungs and kidneys. We
      determined whether transfusion with old RBC injured brain. DESIGN: Prospective,
      controlled animal study. SETTING: University research laboratory. SUBJECTS: Adult
      male Sprague-Dawley rats. INTERVENTIONS: Six-month-old Sprague-Dawley rats lost
      20% total blood volume and then received RBC prepared from equal volume of the
      lost blood. RBC was stored for 1 day (fresh RBC) or 7 days (old RBC, storage
      lesions similar to those of human RBC stored for 28 d). Some rats received IV
      cell-free hemoglobin. These rats were not subjected to hemorrhage and RBC
      transfusion. MEASUREMENTS AND MAIN RESULTS: Rats were subjected to Barnes maze
      and fear conditioning tests from 1 week after blood transfusion. Rats transfused
      with old RBC but not fresh RBC took a longer time to identify the target hole in
      the Barnes maze and had less context-related fear conditioning behavior than
      control rats. Old RBC significantly increased interleukin 6 and ionized calcium
      binding adapter molecule 1 in the hippocampus at 24 hours after the transfusion.
      These effects were attenuated by sulforaphane and minocycline, an antibiotic with
      anti-inflammatory property. Old RBC solution had a higher concentration of cell
      free hemoglobin. Sulforaphane increased haptoglobin, a chelator of cell-free
      hemoglobin. Rats that received cell-free hemoglobin had a pattern of
      neuroinflammation and impairment of learning and memory similar to that of rats
      that received old RBC. CONCLUSIONS: These results provide initial evidence to
      suggest that transfusion of old RBC induces neuroinflammation and impairment of
      learning and memory. These effects may be mediated by cell-free hemoglobin.

PMID- 25860203
TI  - Goal-Directed Resuscitative Interventions During Pediatric Interfacility
      Transport.
AB  - OBJECTIVES: This article reports results of the first National Institutes of
      Health-funded prospective interfacility transport study to determine the effect
      of goal-directed therapy administered by a specialized pediatric team to
      critically ill children with the systemic inflammatory response syndrome. We
      hypothesized that goal-directed therapy during interfacility transport would
      decrease hospital length of stay, prevent multiple organ dysfunction, and reduce
      subsequent ICU interventions. DESIGN: Before-and-after intervention trial.
      SETTING: During interfacility transport of critically ill patients by a
      specialized pediatric transport team, back to a tertiary care children's
      hospital. PATIENTS: Before-and-after intervention trial. DESIGN: Interfacility
      pediatric transport patients, age 1 month to 17 years, with systemic inflammatory
      response syndrome. INTERVENTIONS: Prospective data were collected on all
      pediatric interfacility transport patients with systemic inflammatory response
      syndrome transported by the Angel One Transport team at Arkansas Children's
      Hospital. A 10-month data collection period was followed by institution of a goal
      directed resuscitation protocol. Data were subsequently collected for 10
      additional months followed by comparison of pre- and postintervention groups. All
      transport personnel underwent training with didactics and high-fidelity
      simulation until mastery with goal-directed resuscitation was achieved.
      MEASUREMENTS AND MAIN RESULTS: All transport patients were screened for systemic
      inflammatory response syndrome using established variables and 235 (123
      preintervention and 112 postintervention) were enrolled. Univariate analysis
      revealed shorter hospital stay (11 +/- 15 d vs 7 +/- 10 d; p = 0.02) and fewer
      required therapeutic ICU interventions in the postintervention group (Therapeutic
      Intervention Scoring System-28 Scores, 19.4 +/- 6.8 vs 17.3 +/- 6.6; p = 0.04).
      ICU stay and prevalence of organ dysfunction were not statistically different.
      Multivariable analysis showed a 1.6-day (95% CI, 1.3-2.03; p = 0.02) decrease in
      hospital stay in the postintervention group. CONCLUSIONS: This study suggests
      that goal-directed therapy administered by a specialized pediatric transport team
      has the potential to impact the outcomes of critically ill children. Findings
      from this study should be confirmed across multiple institutions, but have the
      potential to impact the clinical outcomes of critically ill children with
      systemic inflammatory response syndrome.

PMID- 25860204
TI  - Clonidine Restores Pressor Responsiveness to Phenylephrine and Angiotensin II in
      Ovine Sepsis.
AB  - OBJECTIVES: In sepsis, prolonged, sympathetic overstimulation may lead to
      vasopressor-refractory hypotension. We therefore examined the effects of the
      alpha2-adrenergic agonist clonidine on mean arterial pressure, renal sympathetic
      nerve activity, and pressor responsiveness to phenylephrine and angiotensin II
      during hypotensive sepsis in conscious sheep. DESIGN: Interventional study.
      SETTING: Research institute. SUBJECTS: Twelve adult Merino ewes (n = 6 per
      group). INTERVENTIONS: Sepsis was induced by IV infusion of Escherichia coli for
      32 hours. Pressor responses to increasing doses of phenylephrine and angiotensin
      II were measured at baseline and at 24, 28, and 32 hours of sepsis. Sheep were
      treated with clonidine (1 MUg/kg/hr) or saline-vehicle from 24 to 32 hours of
      sepsis. MEASUREMENTS AND MAIN RESULTS: Sepsis was characterized by hypotension
      (~12 mm Hg), increased heart rate (~80 beats/min), increased renal sympathetic
      nerve activity (~70%), and blunted pressor responses to phenylephrine and
      angiotensin II. In vehicle-treated sheep, mean arterial pressure progressively
      declined from 25 to 32 hours of sepsis (73 +/- 3 to 66 +/- 3 mm Hg; p = 0.013)
      while the elevations in heart rate and renal sympathetic nerve activity and
      reduced pressor responsiveness to vasopressors persisted. Clonidine treatment
      prevented the further decline in mean arterial pressure, substantially reduced
      heart rate and renal sympathetic nerve activity and restored pressor
      responsiveness to both phenylephrine and angiotensin II toward preseptic levels.
      CONCLUSIONS: Administration of clonidine during hypotensive sepsis reduced renal
      sympathetic nerve activity, restored vascular sensitivity to both phenylephrine
      and angiotensin II, and resulted in better preservation of arterial pressure.
      Considering these findings, a clinical trial for the use of clonidine in the
      treatment of persistent vasopressor-refractory hypotension in patients with
      septic shock would be worthwhile.

PMID- 25860205
TI  - Extracorporeal Treatment for Metformin Poisoning: Systematic Review and
      Recommendations From the Extracorporeal Treatments in Poisoning Workgroup.
AB  - BACKGROUND: Metformin toxicity, a challenging clinical entity, is associated with
      a mortality of 30%. The role of extracorporeal treatments such as hemodialysis is
      poorly defined at present. Here, the Extracorporeal Treatments In Poisoning
      workgroup, comprising international experts representing diverse professions,
      presents its systematic review and clinical recommendations for extracorporeal
      treatment in metformin poisoning. METHODS: A systematic literature search was
      performed, data extracted, findings summarized, and structured voting statements
      developed. A two-round modified Delphi method was used to achieve consensus on
      voting statements and RAND/UCLA Appropriateness Method to quantify disagreement.
      Anonymized votes and opinions were compiled and discussed. A second vote
      determined the final recommendations. RESULTS: One hundred seventy-five articles
      were identified, including 63 deaths: one observational study, 160 case reports
      or series, 11 studies of descriptive cohorts, and three pharmacokinetic studies
      in end-stage renal disease, yielding a very low quality of evidence for all
      recommendations. The workgroup concluded that metformin is moderately dialyzable
      (level of evidence C) and made the following recommendations: extracorporeal
      treatment is recommended in severe metformin poisoning (1D). Indications for
      extracorporeal treatment include lactate concentration greater than 20 mmol/L
      (1D), pH less than or equal to 7.0 (1D), shock (1D), failure of standard
      supportive measures (1D), and decreased level of consciousness (2D).
      Extracorporeal treatment should be continued until the lactate concentration is
      less than 3 mmol/L (1D) and pH greater than 7.35 (1D), at which time close
      monitoring is warranted to determine the need for additional courses of
      extracorporeal treatment. Intermittent hemodialysis is preferred initially (1D),
      but continuous renal replacement therapies may be considered if hemodialysis is
      unavailable (2D). Repeat extracorporeal treatment sessions may use hemodialysis
      (1D) or continuous renal replacement therapy (1D). CONCLUSION: Metformin
      poisoning with lactic acidosis appears to be amenable to extracorporeal
      treatments. Despite clinical evidence comprised mostly of case reports and
      suboptimal toxicokinetic data, the workgroup recommended extracorporeal removal
      in the case of severe metformin poisoning.

PMID- 25860206
TI  - The risk of erectile dysfunction in chronic obstructive pulmonary disease: a
      population-based cohort study in Taiwan.
AB  - The prevalence of erectile dysfunction (ED) in patients with chronic obstructive
      pulmonary disease (COPD) seemed high; however, large scale of population-based
      study was absent. We conducted a retrospective cohort study using data from the
      National Health Insurance system of Taiwan. The cohort included 29,042 male
      patients who were newly diagnosed with COPD. Patients were recruited between 2000
      and 2011, and the date of diagnosis was defined as the index date. Each patient
      was randomly matched with 1 male person from the general population without COPD
      according to age and the index year. The occurrence of ED was followed up until
      the end of 2011. The hazard ratios of ED were estimated using the Cox
      proportional hazard model after adjusting for age, index year, comorbidities, and
      medications. The overall incidence of ED was 1.88-fold greater in the COPD cohort
      than in the non-COPD cohort (24.9 vs 13.3/1000 person-years, 95% confidence
      interval [CI] = 1.61-2.18). Compared with non-COPD patients, the hazard ratio
      increased with the number of emergency room visits and admissions for COPD from
      1.51 (95% CI 1.29-1.77) to 5.46 (95% CI 3.03-9.84) and from 1.50 (95% CI 1.28
      1.76) to 11.5 (95% CI 5.83-22.6), respectively. Patients with COPD are at a
      significantly higher risk of developing ED compared with the general population
      regardless of age and presence of comorbidity. The results also support that poor
      control of COPD status is a key factor affecting ED development.

PMID- 25860207
TI  - Neurocognitive dysfunction risk alleviation with the use of dexmedetomidine in
      perioperative conditions or as ICU sedation: a meta-analysis.
AB  - Many studies have reported the beneficial effects of dexmedetomidine on
      postoperative neurocognitive function but overall evidence is not as clear. We
      examined this conundrum by meta-analyzing studies that used dexmedetomidine in
      perioperative conditions or as intensive care unit (ICU) sedation and utilized
      reliable neurocognitive assessment tests. The literature search was undertaken
      across several electronic databases including EBSCO, Embase, Google Scholar, Ovid
      SP, PubMed, Scopus, and Web of Science. Literature search was carried out across
      several electronic databases and relevant studies were selected after following
      precised inclusion criteria. Meta-analysis of risk differences (RDs) was carried
      out and subgroup analyses were performed. Twenty studies were selected from which
      data of 2612 individuals were used. Initial dexmedetomidine dose was 0.68 +/-
      0.27 and maintenance dose was 0.54 +/- 0.32 in the trials. Dexmedetomidine
      treatment was associated with significantly lower risk of
      postoperative/postanesthesia neurocognitive dysfunction both in comparison with
      saline-treated controls (RD [95% confidence interval, CI]: -0.17 (-0.30, -0.04);
      P = 0.008) and comparators (-0.16 [-0.28, -0.04]; P = 0.009). In the subgroups
      analyses, however, there was no significant differences between dexmedetomidine
      and controls/comparators when studies with confusion assessment method for ICU
      only (RD: -0.10 (-0.22, 0.02); P = 0.1) or midazolam as comparator only (RD: 
      0.26 (-0.60, 0.07); P = 0.12) were meta-analyzed. Dexmedetomidine use in the
      perioperative conditions or as ICU sedation is associated with lower risk of
      neurocognitive dysfunction. There can be some impact of neurocognitive assessment
      method, drug interactions, and clinical heterogeneity on the overall outcomes of
      this meta-analysis.

PMID- 25860208
TI  - Management of large-vessel vasculitis with FDG-PET: a systematic literature
      review and meta-analysis.
AB  - We aimed to clarify the role of 18F-fluorodeoxyglucose positron emission
      tomography (FDG-PET) in the management of large-vessel vasculitis (LVV), focusing
      on 3 issues which are as follows: describe and determine the different FDG-PET
      criteria for the diagnosis of vascular inflammation, the performance of FDG-PET
      for the diagnosis of large-vessel inflammation in giant cell arteritis (GCA)
      patients, and the performance of FDG-PET to evaluate the disease inflammatory
      activity in Takayasu arteritis (TA) patients. MEDLINE, Cochrane Library, and
      EMBASE database were searched for articles that evaluated the value of FDG-PET in
      LVV, from January 2000 to December 2013. Inclusion criteria were American College
      of Rheumatology criteria for GCA or TA, definition PET positivity threshold, and
      >4 cases included. Sensitivity (Se) and specificity (Sp) of FDG-PET for the
      diagnosis of large-vessel inflammation were calculated from each included
      individual study, and then pooled for meta-analysis with a random-effects model.
      Twenty-one studies (413 patients, 299 controls) were included in the systematic
      review. FDG-PET showed FDG vascular uptake in 70% (288/413) of patients and 7%
      (22/299) of controls. Only vascular uptake equal to or higher than the liver
      uptake was significantly different between GCA/TA patients and controls (P <
      0.001). The meta-analysis of GCA patients (4 studies, 57 patients) shows that FDG
      PET has high Se and Sp for the diagnosis of large-vessel inflammation in GCA
      patients in comparison to controls, with a pooled Se at 90% (95% confidence
      interval [CI], 79%-93%) and a pooled Sp at 98% (95% CI, 94%-99%). The meta
      analysis of TA patients (7 studies, 191 patients) shows that FDG-PET has a pooled
      Se at 87% (95% CI, 78%-93%) and Sp at 73% (95% CI, 63%-81%) for the assessment of
      disease activity in TA, with up to 84% Sp, with studies using National Institutes
      of Health criteria as the disease activity assessment scale. FDG-PET showed good
      performances in the diagnosis of large-vessel inflammation, with higher accuracy
      in GCA patients than in TA patients. Although a vascular uptake equal to or
      higher than the liver uptake appears to be a good criterion for the diagnosis of
      vascular inflammation, further studies are needed to define the threshold of
      significance as well as the clinical significance of the vascular uptake.

PMID- 25860209
TI  - Comparison of UHPLC and HPLC in benzodiazepines analysis of postmortem samples: a
      case-control study.
AB  - The aim of this study was to compare system efficiency and analysis duration
      regarding the solvent consumption and system maintenance in high-pressure liquid
      chromatography (HPLC) and ultra high-pressure liquid chromatography (UHPLC). In a
      case-control study, standard solutions of 7 benzodiazepines (BZs) and 73
      biological samples such as urine, tissue, stomach content, and bile that screened
      positive for BZs were analyzed by HPLC and UHPLC in laboratory of forensic
      toxicology during 2012 to 2013. HPLC analysis was performed using a Knauer by 100
      5 C-18 column (250 mm * 4.6 mm) and Knauer photodiode array detector (PAD). UHPLC
      analysis was performed using Knauer PAD detector with cooling autosampler and
      Eurospher II 100-3 C-18 column (100 mm * 3 mm) and also 2 pumps. The mean
      retention time, standard deviation, flow rate, and repeatability of analytical
      results were compared by using 2 methods. Routine runtimes in HPLC and UHPLC took
      40 and 15 minutes, respectively. Changes in mobile phase composition of the 2
      methods were not required. Flow rate and solvent consumption in UHPLC decreased.
      Diazepam and flurazepam were detected more frequently in biological samples. In
      UHPLC, small particle size and short length of column cause effective separation
      of BZs in a very short time. Reduced flow rate, solvent consumption, and
      injection volume cause more efficiency and less analysis costs. Thus, in the
      detection of BZs, UHPLC is an accurate, sensitive, and fast method with less cost
      of analysis.

PMID- 25860210
TI  - Association between high-density lipoprotein cholesterol and renal function in
      elderly hypertension: a cross-sectional study in Chinese population.
AB  - Few studies have yet investigated the possible association between high-density
      lipoprotein cholesterol (HDL-C) and kidney function in elderly patients with
      primary hypertension. Accordingly, the aim of the present study was to evaluate
      the relationship between HDL-C and kidney function in elderly hypertension. A
      total of 14,644 elderly hypertensive subjects were enrolled in our cross
      sectional study. The patients were categorized based on serum HDL-C level and
      glomerular filtration rate (GFR) value, respectively. One-way analysis of
      variance was used to compare the parameters among different groups. Bonferroni
      correction was performed for multiple comparisons. Analysis of covariance was
      used to control for confounding factors. The significance of difference between 3
      groups and more was determined by chi-square test for categorical variables.
      Serum creatinine and uric acid were negatively related to HDL-C level, whereas
      GFR was positively related to HDL-C level in elderly hypertensive patients
      according to tertiles of HDL-C and tertiles of HDL-C/total cholesterol ratio (all
      P for trends <0.05). The male elderly hypertensive patients showed stronger
      relationship between HDL-C and renal function than the female elderly
      hypertensive subjects. Low HDL-C was associated with renal insufficiency and
      proteinuria in the hypertensive elderly (P < 0.05). The elderly "renal
      hyperfiltrator" appeared to have lower HDL-C level, compared with the "normal
      renal-filtrator" (P < 0.05). There was an inverse "V" shape between HDL-C and GFR
      by GFR strata. Our results point out that there is an association of low HDL-C
      level with impaired kidney function in elderly hypertensive patients. Glomerular
      hyperfiltration may also affect HDL-C level and sex might be an influential
      factor for the association of HDL-C with kidney function in elderly hypertension.

PMID- 25860211
TI  - Quality of post arrest care does not differ by time of day at a specialized
      resuscitation center.
AB  - Previous studies suggest worse outcomes after out-of-hospital cardiac arrest
      (OHCA) at night. We analyzed whether patients admitted after nontraumatic OHCA to
      a resuscitation center received the same quality post arrest care at day and
      night and whether quality of care affected clinical outcomes. We analyzed data of
      OHCA patients with return of spontaneous circulation admitted to the Vienna
      general hospital emergency department between January 2006 and May 2013. Data
      reported include admission time (day defined from 8 AM to 4 PM based on
      staffing), time to initiation of hypothermia, and door-to-balloon time in
      patients with ST-elevation myocardial infarction. Survival and cognitive
      performance at 12 months were assessed. In this retrospective observational
      study, 1059 patients (74% males, n = 784) with a mean age of 58 +/- 16 years were
      analyzed. The vast majority was treated with induced hypothermia (77% of day vs.
      79% of night admissions, P = 0.32) within 1 hour of admission (median time
      admission to cooling 27 (confidence interval [CI]: 10-60) vs. 23 (CI: 11-59)
      minutes day vs. night, P = 0.99). In 298 patients with ST-elevation myocardial
      infarction, median door-to-balloon time did not differ between day and night
      admissions (82 minutes, CI: 60 to 142 for day vs. 86 minutes, CI: 50 to 135 for
      night, P = 0.36). At 12 months, survival was recorded in 238 of 490 day and 275
      of 569 night admissions (49% vs. 48%, P = 0.94%), and a good neurologic outcome
      was recorded in 210 of 490 day and 231 of 569 night admissions (43% vs. 41%, P =
      0.46). Patients admitted to our department after OHCA were equally likely to
      receive timely high-quality postresuscitation care irrespective of time of day.
      Survival and good neurologic outcome at 12 months did not differ between day and
      night admissions. Our results may support the concept of specialized post arrest
      care centers.

PMID- 25860213
TI  - Determinants of survival after sorafenib failure in patients with BCLC-C
      hepatocellular carcinoma in real-world practice.
AB  - Sorafenib may improve progression-free survival (PFS) and overall survival (OS)
      of advanced hepatocellular carcinoma (HCC). However, the survival benefit is
      short lived and survivals after progressive disease (PD) have not been well
      characterized. This study aimed to evaluate the survival predictors of OS and
      postprogression survival (PPS) in advanced HCC patients receiving sorafenib
      treatment. Consecutive 149 HCC patients receiving sorafenib under National Health
      Insurance were retrospectively enrolled. All patients fulfilled the reimbursement
      criteria: Barcelona Clinic Liver Cancer stage C HCC with macroscopic vascular
      invasion or extrahepatic metastasis (Mets), and Child-Pugh class A. Radiologic
      assessment was performed at a 2-month interval using modified Response Evaluation
      Criteria in Solid Tumors. Patients who maintained Eastern Cooperative Oncology
      Group <=2 and Child-Pugh class A at PD were assumed to be candidates for second
      line treatment. During the median follow-up period of 7.5 months (range, 1.1
      18.5), PD developed in 120 (80.5%) patients and 96 (64.4%) deaths occurred. The
      median PFS, OS, and PPS were 2.5, 8.0, and 4.6 months, respectively. In general,
      patients with Mets only had better OS and PPS than those with portal vein
      invasion. Independent predictors of OS include baseline performance status
      (hazard ratio [HR] = 1.956), tumor size (HR = 1.597), alpha-fetoprotein (HR =
      1.869), discontinuation of sorafenib due to liver function deterioration (LD) (HR
      = 6.142), or concurrent PD and LD (HR = 2.661) and PD within 4 months (HR =
      5.164). Independent predictors of PPS include deteriorated performance status (HR
      = 7.680), deteriorated liver functions (HR = 5.603), bilirubin (HR = 2.114),
      early PD (HR = 6.109), and new extrahepatic lesion (HR = 1.804). In 46 candidates
      for second-line trials, development of new extrahepatic lesion independently
      predicts poorer PPS (HR = 3.669). In conclusion performance status, liver
      functions, early disease progression, and progression pattern are important
      determinants of survival after sorafenib failure. These factors should be
      considered in clinical practice and second-line trial designs for patients with
      sorafenib failure.

PMID- 25860214
TI  - Pulmonary chondroid hamartoma with nontuberculous mycobacterial infection: two
      case reports.
AB  - Solitary pulmonary nodules (SPNs) can be manifested in a variety of disorders
      including neoplasms, infection, inflammation, and vascular or congenital
      abnormalities. In addition, they are often accompanied with other pulmonary
      pathologic lesions such as consolidations and several pulmonary disorders present
      as similar pulmonary nodular lesions simultaneously. Diagnostic workup is
      important for these SPNs; however, many physicians often miss the second
      diagnosis for multiple pulmonary lesions with SPNs due to lack of clinical
      suspicion that each pulmonary nodule or pathologic lesion can have each other's
      diagnosis. Herein, we report 2 cases of coexistence of pulmonary chondroid
      hamartoma with nontuberculous mycobacterial (NTM) infection presenting as
      pulmonary nodules and multiple consolidative lesions. A 60-year-old man was
      admitted for the evaluation of multifocal pulmonary lesions including SPN with
      chronic exertional dyspnea. Multiple lung tissues were obtained from each lesion
      through percutaneous transthoracic needle biopsy (PTNB). At the same time,
      bacteriologic examination was performed using respiratory samples obtained by
      bronchoscopy. Based on pathologic and microbiologic results, the patient
      diagnosed as pulmonary chondroid hamartoma with pulmonary NTM infectious disease.
      In addition, a 56-year-old woman visited for the evaluation of a small SPN. The
      SPN was resected surgically for the pathologic examination and turned out to be
      pulmonary chondroid hamartoma. Interestingly, the diagnostic workup revealed that
      the patient had Lady Windermere syndrome which is one of features for
      Mycobacterium avium complex (MAC) pulmonary disease. Both patients were treated
      with the standard antibiotics against MAC as recommended by the ATS/IDSA
      guideline. This is the first report of 2 patients, as far as we know, that
      chondroid hamartoma and NTM disease develop simultaneously in the lung. This
      report emphasizes that physicians should endeavor to confirm the individual
      diagnosis for the various pulmonary abnormal lesions detected at the same time,
      if necessary through multifocal biopsies for each lesion.

PMID- 25860212
TI  - Outcome of hepatitis E virus infection in patients with inflammatory arthritides
      treated with immunosuppressants: a French retrospective multicenter study.
AB  - The clinical presentation and outcome of hepatitis E virus (HEV) infection in
      inflammatory rheumatic diseases are unknown. We aimed to investigate the severity
      of acute HEV infection and the risk of chronic viral replication in patients with
      inflammatory arthritides treated with immunosuppressive drugs. All rheumatology
      and internal medicine practitioners belonging to the Club Rhumatismes et
      Inflammation in France were sent newsletters asking for reports of HEV infection
      and inflammatory arthritides. Baseline characteristics of patients and the course
      of HEV infection were retrospectively assessed by use of a standardized
      questionnaire. From January 2010 to August 2013, we obtained reports of 23 cases
      of HEV infection in patients with rheumatoid arthritis (n = 11), axial
      spondyloarthritis (n = 5), psoriatic arthritis (n = 4), other types of
      arthritides (n = 3). Patients received methotrexate (n = 16), antitumor necrosis
      factor alpha agents (n = 10), rituximab (n = 4), abatacept (n = 2), tocilizumab
      (n = 2), and corticosteroids (n = 10, median dose 6 mg/d, range 2-20). All had
      acute hepatitis: median aspartate and alanine aminotransferase levels were 679
      and 1300 U/L, respectively. Eleven patients were asymptomatic, 4 had jaundice.
      The HEV infection diagnosis relied on positive PCR results for HEV RNA (n = 14
      patients) or anti-HEV IgM positivity (n = 9). Median follow-up was 29 months
      (range 3-55). Treatment included discontinuation of immunosuppressants for 20
      patients and ribavirin treatment for 5. Liver enzyme levels normalized and
      immunosuppressant therapy could be reinitiated in all patients. No chronic
      infection was observed. Acute HEV infection should be considered in patients with
      inflammatory rheumatism and elevated liver enzyme values. The outcome of HEV
      infection seems favorable, with no evolution to chronic hepatitis or fulminant
      liver failure.

PMID- 25860215
TI  - Cytokine profiles contribute to understanding the pathogenic difference between
      Good syndrome and oral lichen planus: two case reports and literature review.
AB  - We described and analyzed the pathogenic difference between Good syndrome (GS)
      and oral lichen planus (OLP) in oral mucosa. Good syndrome (GS) is a rare disease
      characterized by B and T cell immunodeficiency associated with
      hypogammaglobulinemia and thymoma. GS patients frequently develop oral lichenoid
      lesions with lymphocytic infiltration beneath the basal layer. Oral lichen planus
      (OLP) is a chronic inflammatory disease of the oral mucosa characterized by
      destruction of basal cells by Langerhans cells, macrophages, and T lymphocytes.
      Although the histological features of the lesions of both diseases are very
      similar, the pathogenesis of GS in the oral mucosa remains unknown. In this
      study, we thus investigated the expression of infiltrating lymphocyte subsets
      (CD3, CD20, CD4, and CD8) and T helper (Th) cytokines including interferon (IFN)
      gamma (Th1 type), interleukin (IL)-4 (Th2 type), IL-17 (Th17 type), and IL-10
      (regulatory T cell type) by immunohistochemistry in buccal mucosa specimens from
      2 GS patients compared with 15 OLP patients. All patients showed a predominance
      of CD3 T cells over CD20 B cells, and CD4 Th cells over CD8 cytotoxic T cells.
      This polarization was especially prominent in GS. IFN-gamma and IL-10 were
      strongly detected in the infiltrating lymphocytes of all patients. However, IL-4
      and IL-17 were detected in OLP patients only. These results suggest that the
      pathogenesis of GS is different from that of OLP. GS is a unique inflammatory
      disorder characterized by dysfunction of Th2 and Th17 immune reactions via
      abnormal T-B cell interaction.

PMID- 25860216
TI  - Red cell distribution width as a predictor of left atrial spontaneous echo
      contrast in echocardiography.
AB  - Red cell distribution width (RDW) represents the heterogeneity of red blood cells
      (anisocytosis). Spontaneous echo contrast (SEC) is thought to be a manifestation
      of red cell aggregation and it has been linked to the development of
      thromboemboli. The aim of this study was to evaluate the association between RDW
      levels and the presence of left atrial SEC (LASEC). One-hundred and 72 patients
      who underwent transesophageal echocardiography for various indications were
      enrolled in the study. All patients were categorized into 2 groups according to
      the presence of LASEC and into 4 groups according to the severity of LASEC. The
      baseline clinical characteristics, echocardiographic measurements, and laboratory
      findings, including RDW, were compared between the groups. The RDW (%) level was
      higher in the LASEC group (14.95 +/- 1.32) compared with the non-LASEC group
      (12.20 +/- 1.45; P = 0.0001). When the relationship between RDW and SEC was
      evaluated according to the increasing grade of SEC, a significant positive
      correlation was found (r = 0.645, P < 0.0001). In the ROC analysis, an RDW level
      >13.8% had 70% sensitivity and 89.2% specificity in predicting LASEC (area under
      the curve = 0.834, P < 0.0001, 95% CI 0.656-0.773). In multivariate analysis, RDW
      levels >13.8% and the presence of atrial fibrillation were independently
      associated with LASEC (odds ratio [OR] 1.697; 95% confidence interval [CI] 1.198
      2.085; P = 0.001 and OR 1.586; 95% CI 1.195-2.098; P = 0.003, respectively].
      Elevated RDW value is associated with the presence and the severity of SEC. RDW
      may be a useful marker and independent predictor for the presence of SEC.

PMID- 25860217
TI  - Neuroblastoma, body mass index, and survival: a retrospective analysis.
AB  - Extremes of body mass index (BMI) at diagnosis of childhood cancers have been
      associated with poorer prognosis. The aims of this retrospective review were to
      examine the growth and BMI status of children diagnosed with neuroblastoma (NB)
      and determine if BMI status at diagnosis affected survival. Between 1985 and
      2005, 154 children were diagnosed with NB at Sydney Children's Hospitals Network
      (Westmead), Australia, of which 129 had both length/height and weight recorded in
      the medical records at diagnosis. BMI was calculated and children were classified
      as underweight (BMI <15th percentile), normal weight, and overweight (BMI >85th
      percentile). Disease stage was classified according to the International NB
      Staging System. At diagnosis, 24.0% of the children were classified as
      underweight and 11.6% were overweight. Six months after diagnosis all children
      except those with stage 4s disease had a decrease in BMI z-score; difference in
      estimated marginal mean -0.73, P < .001. After 12 months an increase in BMI z
      score was observed and by 2 years BMI z-score was significantly higher than BMI z
      score at baseline; difference in estimated marginal mean 0.81, P = .007. At the
      last follow-up (median 5.6 years [range 3-7] after diagnosis) the proportion of
      children who were classified as underweight decreased to 8.7% and the proportion
      of children who were classified as overweight increased to 27.5%. The overall
      survival rate was 61.2%; however, BMI status did not predict survival. In
      multivariable Cox regression modeling, stage at diagnosis was the only predictor
      of survival; children diagnosed with stage 4 were less likely to survive (hazard
      ratio [HR] [95%CI]: 7.02 [1.7-29.0], P = .007). Almost a quarter of children with
      NB were underweight at diagnosis. However, we did not demonstrate a prognostic
      association between BMI status and survival. The high proportion of children who
      were classified as overweight at follow-up indicates a need for nutritional
      interventions to prevent potential late effects.

PMID- 25860218
TI  - Identification of X monosomy cells from a gonad of mixed gonadal dysgenesis with
      a 46,XY karyotype: case report.
AB  - Mixed gonadal dysgenesis (MGD) is a disorder of sexual development that typically
      has a mosaic 45,X/46,XY karyotype. A 1-year-old infant with 46,XY identified by
      peripheral blood karyotype demonstrated clinical manifestations and gonadal
      pathologic features of MGD. Fluorescence in situ hybridization (FISH) for X and Y
      chromosomes and immunofluorescence for SRY along with testicular and ovarian
      lineage markers SOX9 and FOXL2, respectively, were performed on paraffin sections
      from the gonad to ascertain the somatic mosaic state for 45,X monosomy and 46,XY
      cells. The gonad consisted of cells with X and XY signals, which were further
      quantified in comparison with a normal control testis by a digital image analysis
      program. The average percentages of 45,X cells of this patient's gonad and a
      control testis were 39.0% and 5.7%, respectively (chi2 test, P < 0.001). SRY
      expression was absent in approximately 10% of precursor granulosa cells (FOXL2
      positive) and precursor Sertoli/granulosa cells (both SOX9 and FOXL2 positive)
      within gonadoblastomas, confirming the involvement of 45,X cells. A combination
      of analysis of FISH and immunofluorescence for SRY in the gonadal tissue could
      identify 45,X cells in MGD with 46,XY.

PMID- 25860219
TI  - Anterolateral radical debridement and interbody bone grafting combined with
      transpedicle fixation in the treatment of thoracolumbar spinal tuberculosis.
AB  - This retrospective cohort study was conducted to evaluate the clinical outcomes
      of radical anterolateral debridement and autogenous ilium with rib or titanium
      cage interbody autografting with transpedicle fixation for the treatment of
      thoracolumbar tuberculosis. Spinal tuberculosis operation aims to remove the
      lesions and necrotic tissues, remove spinal cord compression, and reconstruct
      spinal stability. However, traditional operation methods cannot effectively
      correct cyrtosis or stabilize the spine. In addition, the patient needs to stay
      in bed for a long time and may have many complications. So far, the best surgical
      method and fixation method for spinal tuberculosis remain controversial. There
      were a total of 43 patients, 16 involving spinal cord injury, from January 2004
      to January 2011. The patients were surgically treated for radical anterolateral
      debridement via posterolateral incision and autogenous ilium with rib or titanium
      cage interbody autografting and single-stage transpedicle fixation. All the
      patients were followed up to determine the stages of intervertebral bone fusion
      and the corrections of spinal kyphosis with the restoration of neurological
      deficit. The erythrocyte sedimentation rate (ESR) of these patients decreased to
      normal levels for a mean of 2.8 months. The function of feeling, motion, and
      sphincter in 16 paraplegia cases gradually recovered after 1 week to 3 months
      postoperatively, and the American Spinal Injury Association scores significantly
      increased at the final follow-up. Intervertebral bone fusions were all achieved
      postoperatively. No internal fixation devices were loose, extracted, or broken.
      There was no correction degree loss during the follow-up. The method of radical
      anterolateral debridement and autogenous ilium with rib or titanium cage
      interbody autografting and single-stage transpedicle fixation was effective for
      the treatment of thoracolumbar tuberculosis, correcting kyphotic deformity, and
      reconstructing spinal stability, obtaining successful intervertebral bony fusion
      and promoting the recovery of paraplegia. These results showed satisfactory
      clinical outcomes.

PMID- 25860221
TI  - The effects of different preoperative biliary drainage methods on complications
      following pancreaticoduodenectomy.
AB  - The objective of this study was to investigate the effects of different
      preoperative biliary drainage (PBD) methods on complications in jaundiced
      patients following pancreaticoduodenectomy. We retrospectively analyzed 270
      extrahepatic bile duct cancer patients who underwent pancreaticoduodenectomy. A
      total of 170 patients without PBD treatment were defined as the non-PBD group.
      According to different PBD methods, 45, 18, and 37 patients were classified into
      the percutaneous transhepatic biliary drainage (PTBD), endoscopic nasobiliary
      drainage (ENBD), and endoscopic retrograde biliary stent (ERBS) groups,
      respectively. Clinical characteristics and complications were compared among the
      4 groups. Preoperative cholangitis occurred in 14 (8.2%) and 8 (21.6%) patients
      in the non-PBD and ERBS group, respectively (P = 0.04). Compared with the non-PBD
      group, delayed gastric emptying (DGE) and wound infection occurred significantly
      more often in the ERBS group. The incidence of severe complications was
      significantly lower in the PTBD group than the non-PBD group (P = 0.03).
      Postoperative hospital stay and complication rates were significantly higher in
      the ERBS group than the PTBD group. There were no significant differences in
      complications between ENBD and other groups. In conclusion, PTBD can improve
      surgical outcomes by reducing severe complication rate in jaundiced patients
      following pancreaticoduodenectomy. ERBS increased the rates of DGE and wound
      infection due to high incidence of cholangitis before operative intervention and
      should be avoided. ENBD carried no special effect on complications and needs
      further analysis.

PMID- 25860220
TI  - Value of quantitative and qualitative analyses of circulating cell-free DNA as
      diagnostic tools for hepatocellular carcinoma: a meta-analysis.
AB  - Qualitative and quantitative analyses of circulating cell-free DNA (cfDNA) are
      potential methods for the detection of hepatocellular carcinoma (HCC). Many
      studies have evaluated these approaches, but the results have been variable. This
      meta-analysis is the first to synthesize these published results and evaluate the
      use of circulating cfDNA values for HCC diagnosis. All articles that met our
      inclusion criteria were assessed using QUADAS guidelines after the literature
      research. We also investigated 3 subgroups in this meta-analysis: qualitative
      analysis of abnormal concentrations of circulating cfDNA; qualitative analysis of
      single-gene methylation alterations; and multiple analyses combined with alpha
      fetoprotein (AFP). Statistical analyses were performed using the software Stata
      12.0. We synthesized these published results and calculated accuracy measures
      (pooled sensitivity and specificity, positive/negative likelihood ratios
      [PLRs/NLRs], diagnostic odds ratios [DORs], and corresponding 95% confidence
      intervals [95% CIs]). Data were pooled using bivariate generalized linear mixed
      model. Furthermore, summary receiver operating characteristic curves and area
      under the curve (AUC) were used to summarize overall test performance.
      Heterogeneity and publication bias were also examined. A total of 2424 subjects
      included 1280 HCC patients in 22 studies were recruited in this meta-analysis.
      Pooled sensitivity and specificity, PLR, NLR, DOR, AUC, and CIs of quantitative
      analysis were 0.741 (95% CI: 0.610-0.840), 0.851 (95% CI: 0.718-0.927), 4.970
      (95% CI: 2.694-9.169), 0.304 (95% CI: 0.205-0.451), 16.347 (95% CI: 8.250
      32.388), and 0.86 (95% CI: 0.83-0.89), respectively. For qualitative analysis,
      the values were 0.538 (95% CI: 0.401-0.669), 0.944 (95% CI: 0.889-0.972), 9.545
      (95% CI: 5.298-17.196), 0.490 (95% CI: 0.372-0.646), 19.491 (95% CI: 10.458
      36.329), and 0.87 (95% CI: 0.84-0.90), respectively. After combining with AFP
      assay, the values were 0.818 (95% CI: 0.676-0.906), 0.960 (95% CI: 0.873-0.988),
      20.195 (95% CI: 5.973-68.282), 0.190 (95% CI: 0.100-0.359), 106.270 (95% CI:
      22.317-506.055), and 0.96 (95% CI: 0.94-0.97), respectively. The results in this
      meta-analysis suggest that circulating cfDNA have potential value for HCC
      diagnosis. However, it would not be recommended for using independently, which is
      based on the nonrobust results. After combining with AFP, the diagnostic
      performance will be improved. Further investigation with more data is needed.

PMID- 25860222
TI  - Association between anti-TNF therapy for rheumatoid arthritis and hypertension: a
      meta-analysis of randomized controlled trials.
AB  - Tumor necrosis factor (TNF) is an important and pleiotropic cytokine which is
      also involved in the pathogenesis of inflammation in rheumatoid arthritis (RA),
      and RA treated with anti-TNF agents with a subsequent increase in hypertension
      risk is also observed in clinical trials. However, it is confusing that to what
      extent treatment with anti-TNF agents for RA might be associated with increasing
      risk of hypertension. The aim of this study was to investigate the overall
      incidence and risk of hypertension in RA patients who receive anti-TNF agents.
      The databases of Embase, PubMed, the Cochrane Library, and clinical trial
      registration Web site were searched for relevant trials. Statistical analyses
      were conducted to calculate the overall incidence, odds ratios, and 95%
      confidence intervals (CI) by using either random-effects or fixed-effect models
      according to the heterogeneity of the included studies. A total of 6321 subjects
      with RA from 11 randomized clinical trials (RCTs) were included in the meta
      analysis. The overall incidence of hypertension associated with anti-TNF agent
      was 3.25% (95% CI: 1.51%-6.89%). The use of anti-TNF agent significantly
      increased the risk of developing hypertension (OR = 1.8896, 95% CI: 1.35-2.65).
      Sensitivity analysis showed that the OR between anti-TNF therapy and controls is
      not significantly influenced by omitting any single study. No evidence of
      publication bias was observed. Anti-TNF therapy is associated with a
      significantly increased risk of developing hypertension in patients with RA.
      Physicians should be aware of this risk and provide continuing monitoring in
      patients receiving these therapies.

PMID- 25860223
TI  - Comparing a knowledge-driven approach to a supervised machine learning approach
      in large-scale extraction of drug-side effect relationships from free-text
      biomedical literature.
AB  - BACKGROUND: Systems approaches to studying drug-side-effect (drug-SE)
      associations are emerging as an active research area for both drug target
      discovery and drug repositioning. However, a comprehensive drug-SE association
      knowledge base does not exist. In this study, we present a novel knowledge-driven
      (KD) approach to effectively extract a large number of drug-SE pairs from
      published biomedical literature. DATA AND METHODS: For the text corpus, we used
      21,354,075 MEDLINE records (119,085,682 sentences). First, we used known drug-SE
      associations derived from FDA drug labels as prior knowledge to automatically
      find SE-related sentences and abstracts. We then extracted a total of 49,575 drug
      SE pairs from MEDLINE sentences and 180,454 pairs from abstracts. RESULTS: On
      average, the KD approach has achieved a precision of 0.335, a recall of 0.509,
      and an F1 of 0.392, which is significantly better than a SVM-based machine
      learning approach (precision: 0.135, recall: 0.900, F1: 0.233) with a 73.0%
      increase in F1 score. Through integrative analysis, we demonstrate that the
      higher-level phenotypic drug-SE relationships reflects lower-level genetic,
      genomic, and chemical drug mechanisms. In addition, we show that the extracted
      drug-SE pairs can be directly used in drug repositioning. CONCLUSION: In summary,
      we automatically constructed a large-scale higher-level drug phenotype
      relationship knowledge, which can have great potential in computational drug
      discovery.

PMID- 25860224
TI  - Treatment of wounds following breast reduction and mastopexy with subsequent
      wound dehiscence with charged polystyrene microspheres.
AB  - BACKGROUND: Lower T-junction wound dehiscence following breast reduction surgery
      or mastopexy constitutes a vexing and grievous complication both to the surgeon
      and the patient. Treatment modalities that can expedite wound healing and
      reepithelialization rates are highly craved. The objective of this study was to
      assess wound healing and epithelialization rates of open wounds following breast
      reduction and mastopexy wound dehiscence treated with charged polystyrene
      microspheres (CPM). MATERIALS AND METHODS: Five female patients with wound
      dehiscence and subsequent open wounds following breast reduction and mastopexy
      were treated with daily with CPMsoaked dressings. Wound closure rates were
      documented. RESULTS: The wounds showed both accelerated granulation tissue
      formation as well as swift epithelialization rates. No complications or side
      effects were encountered. CONCLUSIONS: Charged polystyrene microspheres may offer
      a new and efficacious way to heal open wounds due to wound dehiscence following
      aesthetic breast surgery. Further research with a larger patient population is
      still needed to verify these findings.    .

PMID- 25860225
TI  - Conversion of an enterocutaneous fistula associated with an open abdominal wound
      into a drain- controlled enterocutaneous fistula.
AB  - Open abdominal wounds with enterocutaneous fistulae present health care providers
      and patients with complex wound management issues. Frequently, large wounds with
      exposed bowel are present and require the utilization of multiple wound care
      modalities to provide a method of control and isolation of fistula effluent to
      allow for maximum wound healing. This case study presents a unique approach to
      management of low-output enterocutaneous fistula with an open abdominal wound.
      Through the use of negative pressure wound therapy, a standard surgical drain,
      and optimized nutrition, fistula drainage was redirected and the abdominal wound
      healed, leaving a drain-controlled. 

PMID- 25860226
TI  - Antiviral Activities of Honey, Royal Jelly, and Acyclovir Against HSV-1.
AB  - INTRODUCTION: Herpes simplex virus type 1 (HSV-1) belongs to the Herpesviridae
      family and genus simplex virus. This virus is usually acquired during childhood
      and is transmitted through direct mucocutaneous contact or droplet infection from
      infected secretions. The aim of the present study was to compare antiviral
      effects of honey, royal jelly, and acyclovir on herpes simplex virus-1 in an
      extra-somatic environment. MATERIALS AND METHODS: Vero cells were cultured in the
      Dulbecco's Modified Eagle's Medium (DMEM) along with 10% fetal bovine serum (FBS)
      in 12-welled microplates. Various dilutions of honey, royal jelly, and acyclovir
      (5, 10, 50, 100, 2500, 500, and 800 MUg/mL) were added to the Vero cells along
      with a 100-virus concentration of TCID50. The plaque assay technique was used to
      evaluate the antiviral activities. RESULTS: The results showed that honey, royal
      jelly, and acyclovir have the highest inhibitory effects on HSV-1 at
      concentrations of 500, 250, and 100 MUg/mL, respectively. In addition, honey,
      royal jelly, and acyclovir decreased the viral load from 70 795 to 43.3, 30, and
      0 PFU/mL at a concentration of 100 MUg/mL, respectively. CONCLUSION: The results
      of the present study showed that honey and royal jelly, which are natural
      products with no reports about their deleterious effect at least in laboratory
      conditions, can be considered alternatives to acyclovir in the treatment of
      herpetic lesions. However, it should be pointed out that further studies are
      necessary to substantiate their efficacy because hard evidence on their
      effectiveness is not available at present.

PMID- 25860227
TI  - [How to write a "contemporary" university history?].

PMID- 25860229
TI  - Spatial versus day-to-day within-lake variability in tropical floodplain lake CH4
      emissions--developing optimized approaches to representative flux measurements.
AB  - Inland waters (lakes, rivers and reservoirs) are now understood to contribute
      large amounts of methane (CH4) to the atmosphere. However, fluxes are poorly
      constrained and there is a need for improved knowledge on spatiotemporal
      variability and on ways of optimizing sampling efforts to yield representative
      emission estimates for different types of aquatic ecosystems. Low-latitude
      floodplain lakes and wetlands are among the most high-emitting environments, and
      here we provide a detailed investigation of spatial and day-to-day variability in
      a shallow floodplain lake in the Pantanal in Brazil over a five-day period. CH4
      flux was dominated by frequent and ubiquitous ebullition. A strong but
      predictable spatial variability (decreasing flux with increasing distance to the
      shore or to littoral vegetation) was found, and this pattern can be addressed by
      sampling along transects from the shore to the center. Although no distinct day
      to-day variability were found, a significant increase in flux was identified from
      measurement day 1 to measurement day 5, which was likely attributable to a
      simultaneous increase in temperature. Our study demonstrates that representative
      emission assessments requires consideration of spatial variability, but also that
      spatial variability patterns are predictable for lakes of this type and may
      therefore be addressed through limited sampling efforts if designed properly
      (e.g., fewer chambers may be used if organized along transects). Such optimized
      assessments of spatial variability are beneficial by allowing more of the
      available sampling resources to focus on assessing temporal variability, thereby
      improving overall flux assessments. 

PMID- 25860228
TI  - Genetic basis of a cognitive complexity metric.
AB  - Relational complexity (RC) is a metric reflecting capacity limitation in
      relational processing. It plays a crucial role in higher cognitive processes and
      is an endophenotype for several disorders. However, the genetic underpinnings of
      complex relational processing have not been investigated. Using the classical
      twin model, we estimated the heritability of RC and genetic overlap with
      intelligence (IQ), reasoning, and working memory in a twin and sibling sample
      aged 15-29 years (N = 787). Further, in an exploratory search for genetic loci
      contributing to RC, we examined associated genetic markers and genes in our
      Discovery sample and selected loci for replication in four independent samples
      (ALSPAC, LBC1936, NTR, NCNG), followed by meta-analysis (N>6500) at the single
      marker level. Twin modelling showed RC is highly heritable (67%), has
      considerable genetic overlap with IQ (59%), and is a major component of genetic
      covariation between reasoning and working memory (72%). At the molecular level,
      we found preliminary support for four single-marker loci (one in the gene DGKB),
      and at a gene-based level for the NPS gene, having influence on cognition. These
      results indicate that genetic sources influencing relational processing are a key
      component of the genetic architecture of broader cognitive abilities. Further,
      they suggest a genetic cascade, whereby genetic factors influencing capacity
      limitation in relational processing have a flow-on effect to more complex
      cognitive traits, including reasoning and working memory, and ultimately, IQ. 

PMID- 25860231
TI  - Hot Electrons Generated from Doped Quantum Dots via Upconversion of Excitons to
      Hot Charge Carriers for Enhanced Photocatalysis.
AB  - We show that hot electrons exhibiting the enhanced photocatalytic activity in H2
      production reaction can be efficiently generated in Mn-doped quantum dots via the
      "upconversion" of the energy of two excitons into the hot charge carriers. The
      sequential two-photon-induced process with the long-lived Mn excited state
      serving as the intermediate state is considered as the pathway generating hot
      electrons. H2 production rate from doped quantum dots is significantly higher
      than that from undoped quantum dots and also exhibited the quadratic increase
      with the light intensity, demonstrating the effectiveness of the hot electrons
      produced in doped quantum dots in photocatalytic reaction. Due to the very long
      lifetime of Mn excited state (~6 ms) in the doped quantum dots, the sequential
      two-photon excitation requires relatively low excitation rates readily achievable
      with a moderately concentrated solar radiation, demonstrating their potential as
      an efficient source of hot electrons operating at low excitation intensities. 

PMID- 25860230
TI  - Selective homocysteine-lowering gene transfer attenuates pressure overload
      induced cardiomyopathy via reduced oxidative stress.
AB  - Plasma homocysteine levels predict heart failure incidence in prospective
      epidemiological studies. We evaluated whether selective homocysteine-lowering
      gene transfer beneficially affects cardiac remodeling and function in a model of
      pressure overload-induced cardiomyopathy induced by transverse aortic
      constriction (TAC). Female C57BL/6 low-density lipoprotein receptor (Ldlr (-/-))
      cystathionine-beta-synthase (Cbs (+/-)) mice were fed standard chow (control
      mice) or a folate-depleted, methionine-enriched diet to induce
      hyperhomocysteinemia (diet mice). Three weeks after initiation of thisdiet, mice
      were intravenously injected with 5 * 10(10) viral particles of an E1E3E4-deleted
      hepatocyte-specific adenoviral vector expressing Cbs (AdCBS), with the same dose
      of control vector, or with saline buffer. TAC or sham operation was performed 2
      weeks later. AdCBS gene transfer resulted in 86.4 % (p < 0.001) and 84.6 % (p <
      0.001) lower homocysteine levels in diet sham mice and diet TAC mice,
      respectively. Mortality rate was significantly reduced in diet AdCBS TAC mice
      compared to diet TAC mice during a follow-up period of 8 weeks (hazard ratio for
      mortality 0.495, 95 % CI 0.249 to 0.985). Left ventricular hypertrophy (p < 0.01)
      and interstitial myocardial fibrosis (p < 0.001) were strikingly lower in control
      TAC mice and diet AdCBS TAC mice compared to diet TAC mice. Diastolic function in
      diet AdCBS TAC mice was similar to that of control TAC mice and was significantly
      improved compared to diet TACmice. AdCBS gene transfer potently reduced oxidative
      stress as evidenced by a reduction of plasma TBARS and a reduction of myocardial
      3-nitrotyrosine-positive area (%). In conclusion, selective homocysteine lowering
      potently attenuates pressure overload-induced cardiomyopathy via reduced
      oxidative stress. KEY MESSAGE: Plasma homocysteine levels predict heart failure
      incidence in epidemiological studies. Transverse aortic constriction (TAC)
      induces pressure overload. Selective homocysteine-lowering gene therapy reduces
      mortality after TAC. Selective homocysteine lowering attenuates cardiac
      hypertrophy and fibrosis after TAC. Decreased homocysteine levels enhance
      diastolic function and lower oxidative stress.

PMID- 25860232
TI  - Clinical and prognostic differences among patients with light chain deposition
      disease, myeloma cast nephropathy and both.
AB  - In some patients with light chain deposition disease (LCDD) there is also
      evidence of myeloma cast nephropathy (MCN) on renal biopsy. The purpose of this
      study was to evaluate the renal and survival outcome of patients with concomitant
      diagnosis of MCN and LCDD to LCDD and MCN alone. Eighty seven patients were
      identified and divided into LCDD (n=45), MCN (n=29), and LCDD+ MCN (n=13).
      Patients with LCDD+ MCN had a worse overall survival (OS) compared to patients
      with LCDD (p=0.03), but similar to patients with MCN (p=0.4). Death-censored
      renal survival was no different amongst the groups. Presenting with acute renal
      failure at time of renal biopsy (HR 7.2, p=0.0002) was an independent poor renal
      prognostic factor while older age (HR 1.06, p=0.0002), presence of osteolytic
      lesions (HR 4.4, p<0.0001), and requirement for dialysis or creatinine>=5 mg/dL
      (HR 3.2, p=0.0006) at time of renal biopsy were independent poor prognostic
      factors for OS.

PMID- 25860233
TI  - Economic impact of disease progression following front-line therapy in classical
      Hodgkin lymphoma.
AB  - The current study aimed to assess the economic burden of progressive disease
      among patients with Hodgkin lymphoma (HL) receiving second- or third-line therapy
      in a large US network of community-based practices. This retrospective,
      observational cohort analysis used electronic health records to examine adult
      patients with classical HL who received chemotherapy between 2007 and 2011. Of
      291 observations, 112 had non-progressive disease (received only one line of
      therapy; LOT1), 114 received second-line therapy (LOT2), and 65 received third
      line therapy (LOT3). In LOT2, 49 patients (43%) underwent transplant. In LOT3, 13
      patients (20%) underwent transplant. The mean total cost per line of therapy was
      $21 956 in LOT1, $77 219 in LOT2, and $59 442 in LOT3. When transplant was
      required, the mean total cost per line of therapy increased 7- to 8-fold when
      compared with the cost of LOT1 (approximately $154 000 for LOT2 and $193 000 for
      LOT3). Future therapies that intervene as early as possible in the treatment
      algorithm to prevent or significantly delay relapse will likely result in
      significant cost savings. 

PMID- 25860234
TI  - Isotype-switched follicular lymphoma displays dissociation between activation
      induced cytidine deaminase expression and somatic hypermutation.
AB  - In B-cells, activation-induced cytidine deaminase (AID) is required for somatic
      hypermutation (SHM) and class switch recombination (CSR) of immunoglobulin genes.
      AID introduces mutations in immunoglobulin variable regions (IGV) during B-cell
      receptor affinity maturation, but may also introduce aberrant mutations into non
      immunoglobulin genes, most commonly BCL6. Follicular lymphoma (FL) B-cells
      constitutively express AID and undergo CSR, SHM and aberrant SHM. We have studied
      AID expression, the presence of SHM mutations, CSR, and aberrant SHM in BCL6 in a
      cohort of 75 FL patients. Whereas IgM-expressing (non-switched) FL were
      characterized by an expected positive correlation between AID and IGV and BCL6
      mutations, isotype-switched FL showed dissociation between AID expression and
      aberrant SHM, and inverse correlation between SHM and AID expression. Our results
      unveil two manifest biological subgroups of FL and indicate that the specific
      dissociation between AID and SHM after isotype switch may correlate with the
      clinical outcome of this heterogeneous disease. 

PMID- 25860235
TI  - A unique acute myeloid leukemia patient with cryptic NUP98-NSD1 gene and ASXL1
      mutation.

PMID- 25860236
TI  - Incidence, clinical and biological characteristics and outcome of secondary acute
      lymphoblastic leukemia after solid organ or hematologic malignancy.
AB  - Acute lymphoblastic leukemia (ALL) following solid organ or hematologic
      malignancy (secondary ALL, s-ALL) is not well characterized. We analyzed the
      characteristics and outcome of patients with s-ALL and compared them with those
      of patients with de novo- ALL. Of 448 patients, 24 (5%) had previous neoplasia.
      Sixteen patients had received previous cytotoxic therapy (therapy-associated ALL,
      t-ALL), and eight had not (antecedent-malignancy ALL, am-ALL). Except for more
      advanced age in patients with s-ALL, no statistically significant differences
      were observed in WBC count, CNS involvement, immunophenotype or cytogenetics
      between the groups, nor in complete remission (t-ALL: 94%; am-ALL: 75%; de novo
      ALL: 85%), 3-year remission duration (58%; 50%; 72%), overall survival (71%; 38%;
      60%) or event-free survival (53%, 38%; 53%). Our study did not show poor clinical
      or cytogenetic features or inferior outcome in ALL patients with antecedent
      neoplastic disease, irrespective of the type of treatment received for the
      neoplasia. 

PMID- 25860237
TI  - Primary cutaneous B-cell lymphoma (non-leg type) has excellent outcomes even
      after very low dose radiation as single-modality therapy.
AB  - Primary cutaneous B cell lymphomas (PCBCL) are rare; although data on outcomes
      and treatment are limited, traditionally they have been treated with radiation
      doses in excess of 24 Gy. We retrospectively identified and reviewed all cases of
      PCBCL treated at our institution from 2002-2014. Thirty-nine patients with PCBCL
      (42 lesions) were identified. Radiation was the only treatment for most patients.
      All lesions had a complete response and none had in-field failures; seven
      patients had out-of-field relapses, three of which were salvaged with radiation
      therapy. No differences in PFS or OS were found for patients given low-dose (<=
      12 Gy) versus high-dose (> 12 Gy) radiation. PCBCL is an indolent entity with a
      long clinical course and excellent response to radiation therapy and successful
      salvage of recurrent disease, even when doses are as low as 4 Gy. Given the above
      findings, we recommend the initial use of low-dose irradiation for PCBCL. 

PMID- 25860238
TI  - Loss of HLA-DR expression is related to tumor microenvironment and predicts
      adverse outcome in diffuse large B-cell lymphoma.
AB  - The interaction between tumor cells and the tumor microenvironment is essential
      in the development and progression of diffuse large B-cell lymphoma (DLBCL). Loss
      of human leukocyte antigen DR (HLA-DR) in DLBCL is a robust adverse prognostic
      marker. We evaluated the immunohitochemical expression of HLA-DR in lymphoma and
      the biologic implications of the loss of HLA-DR. The loss of HLA-DR correlated
      with clinical stage (p < 0.05), International Prognosis Index (p < 0.05), soluble
      interleukin-2 receptor (p < 0.05) and poor outcome in patients with DLBCL,
      especially among elderly patients. Flow cytometry analysis of the infiltrating T
      cells showed that the mean CD4 + CD25 +/CD8 ratio of the infiltrating T-cells was
      higher in the HLA-DR positive group than in the HLA-DR negative group (p < 0.05).
      These data suggest that loss of HLA-DR expression in DLBCL decreases the ratio of
      helper T-cell within the T-cell population in the tumor microenvironment and
      might contribute to escape from immunosurveillance. 

PMID- 25860239
TI  - High incidence of intact or fragmented immunoglobulin in urine of patients with
      multiple myeloma.
AB  - In this prospective study we determined the incidence of intact/fragmented
      immunoglobulin and Bence Jones protein in urine immunofixation using Sebia
      reagents and HydrasysTM 2 apparatus and compared the results to concentrations of
      serum free light chains (FLC) assessed using Siemens BNTM II nephelometer and the
      immunoassay Freelite (Binding Site) in 289 patients with multiple myeloma at
      diagnosis. It was found that in one third of IgG, IgA and IgD myeloma patients,
      intact/fragmented immunoglobulin can be detected in urine and is connected with
      impaired renal function and reduced survival. Urine immunofixation detects
      monoclonal protein (FLC and intact/fragmented immunoglobulin) in 66-79% of IgG
      and IgA myeloma patients while serum FLC immunoassay detect it in 82-94% of IgG
      and IgA myeloma patients. However, the latter method is inadequate for detection
      of intact/fragmented immunoglobulin in urine. Serum FLC immunoassay and urine
      immunofixation are complementary methods in diagnosing and monitoring monoclonal
      protein in patients with myeloma.

PMID- 25860241
TI  - Serum ferritin as prognostic marker in classical Hodgkin lymphoma treated with
      ABVD-based therapy.
AB  - Ferritin levels might correlate with disease activity in classical Hodgkin
      lymphoma (cHL). We analyzed the prognostic significance of the ferritin value at
      diagnosis in 173 cHL patients treated with ABVD between 2003 and 2013. The 5-year
      overall survival (OS) and progression-free survival (PFS) probabilities were 80%
      and 64%, respectively. Patients with ferritin >= 350 MUg/l [high ferritin group
      (HF), n = 62] were more likely to have advanced stage disease, B-symptoms and
      higher International Prognostic Score (IPS) compared with patients with ferritin
      < 350 MUg/l [low ferritin group (LF), n = 111]. The complete remission (CR) rate
      and 5-year PFS and OS probabilities were lower in HF vs. LF patients (69% vs.
      89%, p = 0.025; 40% vs. 78%, p < 0.001; 61% vs. 90%, p = 0.001; respectively).
      Multivariate analysis revealed that advanced stage (p = 0.001) and ferritin
      levels >= 350 MUg/l (p = 0.002) were independent predictors for PFS. In
      conclusion, the ferritin level at diagnosis is a useful prognostic marker for
      cHL. 

PMID- 25860240
TI  - Novel therapies for myelofibrosis.
AB  - Myelofibrosis (MF), including primary, post-essential thrombocythemia and post
      polycythemia vera MF, associates with a reduced quality of life and shortened
      life expectancy. Dysregulation of the Janus kinase (JAK)/signal transducer and
      activator of transcription (STAT) pathway is prominent, even in the absence of
      the JAK2(V617F) mutation. Therefore, all symptomatic MF patients may potentially
      derive benefit from JAK inhibitors. Despite the efficacy of JAK inhibitors in
      controlling signs and symptoms of MF, they do not eradicate the disease.
      Therefore, JAK inhibitors are currently being tested in combination with other
      novel therapies, a strategy which may be more effective in reducing disease
      burden, either by overcoming JAK inhibitor resistance or targeting additional
      mechanisms of pathogenesis. Additional targets include modulators of epigenetic
      regulation, pathways that work downstream from JAK/STAT (i.e. mammalian target of
      rapamycin/AKT/phosphoinositide 3-kinase) heat shock protein 90, hedgehog
      signaling, pro-fibrotic factors, abnormal megakaryocytes and telomerase. In this
      review, we discuss novel MF therapeutic strategies. 

PMID- 25860242
TI  - Emergence of del(20q) in a patient in molecular remission of chronic myelogenous
      leukemia during imatinib treatment, with reduction following imatinib
      discontinuation.

PMID- 25860243
TI  - Association between gene and miRNA expression profiles and stereotyped subset #4
      B-cell receptor in chronic lymphocytic leukemia.
AB  - In this study we investigated specific biological and clinical features
      associated with chronic lymphocytic leukemia (CLL) patients carrying stereotyped
      BCR subset #4 (IGHV4-34) among a prospective cohort of 462 CLL/MBL patients in
      early stage (Binet A). All subset #4 patients (n = 16) were characterized by the
      IGHV mutated gene configuration, and absence of unfavorable cytogenetic lesions,
      NOTCH1 or SF3B1 mutations. Gene and miRNA expression profiling evidenced that the
      leukemic cells of subset #4 cases showed significant downregulation of WDFY4,
      MF2A and upregulation of PDGFA, FGFR1 and TFEC gene transcripts, as well as the
      upregulation of miR-497 and miR-29c. The transfection of miR-497 mimic in primary
      leukemic CLL cells induced a downregulation of BCL2, a known validated target of
      this miRNA. Our data identify biological characteristics associated with subset
      #4 patients, providing further evidence for the putative role of BCR in shaping
      the features of the tumor cells in CLL. 

PMID- 25860244
TI  - Modulation of cereblon levels by anti-myeloma agents.
AB  - The use of thalidomide derivatives (IMIDs) has improved multiple myeloma
      prognosis, through an unknown mechanism of action. Recently one molecular target,
      the cereblon (CRBN) protein, has been identified. CRBN acts by binding to DDB1
      CUL4-ROC1 forming a ubiquitin ligase multiprotein complex. We have generated
      antibodies to different regions of CRBN protein, and analyzed the biological
      consequences of augmenting or decreasing CRBN levels. CRBN was expressed in all
      the myeloma cell lines tested, independently of their sensitivity to IMIDs, and
      the CRBN-DDB1-CUL4 complex was efficiently formed. At the molecular level, long
      term treatment with IMIDs induced a slight decrease in CRBN levels and a
      reduction in the CRBN-DDB1-CUL4 complex. Interestingly, treatment with other anti
      myeloma drugs downregulated cellular contents of CRBN, and in a much faster
      fashion. These results suggest that CRBN is an important mediator of the cellular
      response to IMIDs, but also critical in the maintenance of cell viability and/or
      proliferation. 

PMID- 25860245
TI  - The novel kinesin spindle protein (KSP) inhibitor SB-743921 exhibits marked
      activity in in vivo and in vitro models of aggressive large B-cell lymphoma.
AB  - The kinesin spindle protein (KSP) is a mitotic protein essential for cell cycle
      control and motility. SB-743921 (hereafter SB-921) is an inhibitor that
      selectively targets the ATP-binding domain of the KSP. The preclinical activity
      of SB-921 was evaluated in models of diffuse large B-cell lymphoma (DLBCL). The
      cytotoxicity of SB-921 was evaluated in a series of germinal center (GC-DLBCL)
      and post-germinal center (ABC-DLBCL) DLBCL cell lines and a murine lymphoma
      xenograft model. GC-DLBCL lines generally demonstrated greater sensitivity to SB
      921. IC50 values ranged between 1 nM and 900 nM for GC-DLBCL compared to 1 nM to
      10 MUM for ABC lines. SB-921 demonstrated marked activity in a xenograft model of
      Ly-1 (GC-DLBCL). While SB-921 was relatively more active in GC derived cell
      lines, ABC-derived lines still underwent apoptosis at higher concentrations.
      These results demonstrate that SB-921 inhibits proliferation and induces
      apoptosis in both GC-DLBCL and ABC-DLBCL. 

PMID- 25860246
TI  - Outcomes of acute myeloid leukemia with t(15;17) not associated with acute
      promyelocytic leukemia.

PMID- 25860247
TI  - Chronic lymphocytic leukemia/small lymphocytic lymphoma: another neoplasm related
      to the B-cell follicle?
AB  - Although there has been increased attention paid to the critical nature of nodal
      involvement in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL),
      the B-cell compartment it is most closely related to and its relationship to the
      follicle remain uncertain. A clinicopathologic investigation of 60 extramedullary
      biopsies of LEF1+ CLL/SLL, including 29 cases with perifollicular/follicular
      (PF/F) growth, was therefore performed. A subset of PF/F cases demonstrated inner
      mantle zone preservation or intra-mantle zone growth. All PF/F and 16/31 other
      cases contained CD21+ follicular dendritic cells. No cytogenetic, IGHV mutational
      or gene usage differences were seen between PF/F and diffuse cases. PF/F cases
      were more often kappa positive (p<0.03) and had fewer involved nodal sites
      (p=0.0004). These findings suggest that at least a subset of bona fide CLL/SLL is
      related to the follicle, most likely the outer mantle zone, and that at least a
      subset of the diffuse cases may represent "later" disease.

PMID- 25860248
TI  - Circulating TNF receptors 1 and 2 are associated with the severity of renal
      interstitial fibrosis in IgA nephropathy.
AB  - The current study aimed to examine whether the levels of TNF receptors 1 and 2
      (TNFR1 and TNFR2) in serum and urine were associated with other markers of kidney
      injury and renal histological findings, including TNFR expression, in IgA
      nephropathy (IgAN). The levels of the parameters of interest were measured by
      immunoassay in 106 biopsy-proven IgAN patients using samples obtained immediately
      before renal biopsy and in 34 healthy subjects. Renal histological findings were
      evaluated using immunohistochemistry. The levels of serum TNFRs were higher in
      IgAN patients than in healthy subjects. The levels of both TNFRs in serum or
      urine were strongly correlated with each other (r > 0.9). Serum TNFR levels were
      positively correlated with the urinary protein to creatinine ratio (UPCR) and
      four markers of tubular damage of interest (N-acetyl-beta-D-glucosaminidase
      [NAG], beta2 microglobulin [beta2m], liver-type fatty acid-binding protein [L
      FABP], and kidney injury molecule-1 [KIM-1]) and negatively correlated with
      estimated glomerular filtration rate (eGFR). Patients in the highest tertile of
      serum TNFR levels showed more severe renal interstitial fibrosis than did those
      in the lowest or second tertiles. The tubulointerstitial TNFR2-, but not TNFR1-,
      positive area was significantly correlated with the serum levels of TNFRs and
      eGFR. Stepwise multiple regression analysis revealed that elevated serum TNFR1 or
      TNFR2 levels were a significant determinant of renal interstitial fibrosis after
      adjusting for eGFR, UPCR, and other markers of tubular damage. In conclusion,
      elevated serum TNFR levels were significantly associated with the severity of
      renal interstitial fibrosis in IgAN patients. However, the source of TNFRs in
      serum and urine remains unclear. 

PMID- 25860249
TI  - Comparative genomic analysis identifies divergent genomic features of pathogenic
      Enterococcus cecorum including a type IC CRISPR-Cas system, a capsule locus, an
      epa-like locus, and putative host tissue binding proteins.
AB  - Enterococcus cecorum (EC) is the dominant enteric commensal of adult chickens and
      contributes to the gut consortia of many avian and mammalian species. While EC
      infection is an uncommon zoonosis, like other enterococcal species it can cause
      life-threating nosocomial infection in people. In contrast to other enterococci
      which are considered opportunistic pathogens, emerging pathogenic strains of EC
      cause outbreaks of musculoskeletal disease in broiler chickens. Typical morbidity
      and mortality is comparable to other important infectious diseases of poultry. In
      molecular epidemiologic studies, pathogenic EC strains were found to be
      genetically clonal. These findings suggested acquisition of specific virulence
      determinants by pathogenic EC. To identify divergent genomic features and
      acquired virulence determinants in pathogenic EC; comparative genomic analysis
      was performed on genomes of 3 pathogenic and 3 commensal strains of EC.
      Pathogenic isolates had smaller genomes with a higher GC content, and they
      demonstrated large regions of synteny compared to commensal isolates. A molecular
      phylogenetic analysis demonstrated sequence divergence in pathogenic EC genomes.
      At a threshold of 98% identity, 414 predicted proteins were identified that were
      highly conserved in pathogenic EC but not in commensal EC. Among these, divergent
      CRISPR-cas defense loci were observed. In commensal EC, the type IIA arrangement
      typical for enterococci was present; however, pathogenic EC had a type IC locus,
      which is novel in enterococci but commonly observed in streptococci. Potential
      mediators of virulence identified in this analysis included a polysaccharide
      capsular locus similar to that recently described for E. faecium, an epa-like
      locus, and cell wall associated proteins which may bind host extracellular
      matrix. This analysis identified specific genomic regions, coding sequences, and
      predicted proteins which may be related to the divergent evolution and increased
      virulence of emerging pathogenic strains of EC. 

PMID- 25860251
TI  - Organizing radical species in the solid state with halogen bonding.
AB  - The electronic properties (conductivity, magnetism) of radical systems in the
      solid state essentially depend on (1) the extent of delocalization of the spin
      density in the molecule and (2) the intermolecular interactions between radicals.
      The halogen bond has proven very efficient in engineering such magnetic or
      conducting structures and recent advances along these lines are reviewed here.
      Three situations are considered: (1) halogenated radical species acting as
      halogen bond donors, as found in iodotetrathiafulvalene-based chiral conductors
      or bilayer systems, and in spin crossover (SCO) complexes with halogenated
      ligands, (2) radical species acting as halogen bond acceptors, such as neutral
      nitronyl species or anionic, mixed-valence dithiolene complexes, interacting with
      closed-shell halogen bond donors (iodoperfluoro alkanes and arenes, iodo- or
      bromo-pyridinium cations), and, finally, (3) charge transfer salts where both
      halogen bond donor and acceptor are radical species. 

PMID- 25860252
TI  - Chemical methods for protein ubiquitination.
AB  - In eukaryotic cells, many proteins undergo extensive post-translational
      modifications (PTMs) such as methylation, acetylation, phosphorylation,
      glycosylation, and ubiquitination. Among these, ubiquitination is a particularly
      interesting PTM from both structural and functional viewpoints. In
      ubiquitination, the C-terminal carboxyl group of the small ubiquitin protein is
      attached to the epsilon-amine of a lysine residue of a substrate protein through
      an isopeptide bond. Ubiquitination has been shown to be involved in the
      regulation of many cellular processes including protein degradation and gene
      expression. And dysfunction of these processes is implicated in many human
      diseases. Despite many years of intensive research, a large number of protein
      ubquitination events remain poorly characterized. The challenge lies with the
      tremendous difficulties in isolating homogeneously modified proteins from
      biological samples for structural and functional studies. Enzymatic
      ubiquitination in vitro often has limited practical value due to the large number
      of substrate-specific E3 ligases and the difficulties in identifying or isolating
      these enzymes. Chemical approaches to the preparation of ubiquitinated proteins
      provide a powerful solution, and the development of such approaches has been the
      subject of intense research by many research laboratories. This review summarizes
      the methodological developments of protein chemical ubiquitination in recent
      years. 

PMID- 25860250
TI  - Social Isolation During Adolescence Strengthens Retention of Fear Memories and
      Facilitates Induction of Late-Phase Long-Term Potentiation.
AB  - Social isolation during the vulnerable period of adolescence produces emotional
      dysregulation that often manifests as abnormal behavior in adulthood. The
      enduring consequence of isolation might be caused by a weakened ability to forget
      unpleasant memories. However, it remains unclear whether isolation affects
      unpleasant memories. To address this, we used a model of associative learning to
      induce the fear memories and evaluated the influence of isolation mice during
      adolescence on the subsequent retention of fear memories and its underlying
      cellular mechanisms. Following adolescent social isolation, we found that mice
      decreased their social interaction time and had an increase in anxiety-related
      behavior. Interestingly, when we assessed memory retention, we found that
      isolated mice were unable to forget aversive memories when tested 4 weeks after
      the original event. Consistent with this, we observed that a single train of high
      frequency stimulation (HFS) enabled a late-phase long-term potentiation (L-LTP)
      in the hippocampal CA1 region of isolated mice, whereas only an early-phase LTP
      was observed with the same stimulation in the control mice. Social isolation
      during adolescence also increased brain-derived neurotrophic factor (BDNF)
      expression in the hippocampus, and application of a tropomyosin-related kinase B
      (TrkB) receptor inhibitor ameliorated the facilitated L-LTP seen after isolation.
      Together, our results suggest that adolescent isolation may result in mental
      disorders during adulthood and that this may stem from an inability to forget the
      unpleasant memories via BDNF-mediated synaptic plasticity. These findings may
      give us a new strategy to prevent mental disorders caused by persistent
      unpleasant memories.

PMID- 25860253
TI  - Dynamical Processes in Open Quantum Systems from a TDDFT Perspective: Resonances
      and Electron Photoemission.
AB  - We present a review of different computational methods to describe time-dependent
      phenomena in open quantum systems and their extension to a density-functional
      framework. We focus the discussion on electron emission processes in atoms and
      molecules addressing excited-state lifetimes and dissipative processes. Initially
      we analyze the concept of an electronic resonance, a central concept in
      spectroscopy associated with a metastable state from which an electron eventually
      escapes (electronic lifetime). Resonances play a fundamental role in many time
      dependent molecular phenomena but can be rationalized from a time-independent
      context in terms of scattering states. We introduce the method of complex
      scaling, which is used to capture resonant states as localized states in the
      spirit of usual bound-state methods, and work on its extension to static and time
      dependent density-functional theory. In a time-dependent setting, complex scaling
      can be used to describe excitations in the continuum as well as wave packet
      dynamics leading to electron emission. This process can also be treated by using
      open boundary conditions which allow time-dependent simulations of emission
      processes without artificial reflections at the boundaries (i.e., borders of the
      simulation box). We compare in detail different schemes to implement open
      boundaries, namely transparent boundaries using Green functions, and absorbing
      boundaries in the form of complex absorbing potentials and mask functions. The
      last two are regularly used together with time-dependent density-functional
      theory to describe the electron emission dynamics of atoms and molecules.
      Finally, we discuss approaches to the calculation of energy and angle-resolved
      time-dependent pump-probe photoelectron spectroscopy of molecular systems. 

PMID- 25860254
TI  - Interplay Between Mechanochemistry and Sonochemistry.
AB  - Ultrasonic irradiation-based mechanochemical strategies have recently been the
      subject of intensive investigation because of the advantages they offer. These
      include simplicity, energy savings and wide applicability. Traditional areas of
      sonoprocessing such as cleaning, efficient mixing and solid activation have been
      extended to both macromolecular and micro/nanostructures, some of which are
      biologically significant, ultrasound-responsive actuators and crystal design,
      among others. Unlike conventional mechanochemical protocols, which require little
      solvent usage if any at all, mechanical (and chemical) effects promoted by
      ultrasound are observed in a liquid medium. Tensile forces, which share
      similarities with solid mechanochemistry, are generated by virtue of nonlinear
      effects, notably cavitation, when high-amplitude waves propagate in a fluid. This
      work aims to provide insight into some recent developments in the multifaceted
      field of sono-mechanochemistry using various examples that illustrate the role of
      ultrasonic activation, which is capable of boosting hitherto sterile
      transformations and inventing new crafts in applied chemistry. After a
      preliminary discussion of acoustics, which is intended to provide a mechanistic
      background, we mainly focus on experimental developments, while we often mention
      emerging science and occasionally delve into theoretical models and force
      simulations. 

PMID- 25860255
TI  - Supramolecular Chemistry and Mechanochemistry of Macromolecules: Recent Advances
      by Single-Molecule Force Spectroscopy.
AB  - Atomic force spectroscopy (AFM)-based single-molecule force spectroscopy (SMFS)
      was invented in the 1990s. Since then, SMFS has been developed into a powerful
      tool to study the inter- and intra-molecular interactions of macromolecules.
      Using SMFS, a number of problems in the field of supramolecular chemistry and
      mechanochemistry have been studied at the single-molecule level, which are not
      accessible by traditional ensemble characterization methods. In this review, the
      principles of SMFS are introduced, followed by the discussion of several problems
      of contemporary interest at the interface of supramolecular chemistry and
      mechanochemistry of macromolecules, including single-chain elasticity of
      macromolecules, interactions between water and macromolecules, interactions
      between macromolecules and solid surface, and the interactions in supramolecular
      polymers. 

PMID- 25860256
TI  - Effects of metal oxide nanoparticles on the stability of dispersions of weakly
      charged colloids.
AB  - The stability behavior of dispersions of weakly charged silica colloids was
      studied in the presence of highly charged metal oxide nanoparticles. Experiments
      were performed using 5 nm zirconia as well as 10 nm alumina nanoparticles (both
      positively charged), which were added to 0.1 vol % suspensions of 1.0 MUm silica
      microparticles at the silica IEP. Both types of nanoparticles provided effective
      stabilization of the silica; i.e., the silica suspensions were stabilized for
      longer than the observation period (greater than 12 h). Stability was observed at
      zirconia concentrations as low as 10(-4) vol % and at an alumina concentration of
      10(-2) vol %. The nanoparticles adsorbed onto the microparticle surfaces
      (confirmed via SEM imaging), which increased the zeta-potential of the silica.
      Force profile measurements performed with colloidal probe atomic force microscopy
      showed that the adsorption was effectively irreversible. 

PMID- 25860258
TI  - Performance of kala-azar surveillance in Gaffargaon subdistrict of Mymensingh,
      Bangladesh.
AB  - INTRODUCTION: Elimination of kala-azar is planned for South Asia requiring good
      surveillance along with other strategies. We assessed surveillance in Gaffargaon
      upazila (a subdistrict of 13 unions) of Mymensingh district, Bangladesh highly
      endemic for kala-azar. METHODS: In 4703 randomly sampled households, within nine
      randomly sampled villages, drawn from three randomly sampled unions, we actively
      searched for kala-azar cases that had occurred between January 2010 and December
      2011. We then searched for medical records of these cases in the patient
      registers of Gaffargaon upazila health complex (UHC). We investigated factors
      associated with the medical recording by interviewing the cases and their
      families. We also did a general observation of UHC recording systems and
      interviewed health staff responsible for the monthly reports of kala-azar cases.
      RESULTS: Our active case finding detected 58 cases, but 29 were not recorded in
      the Gaffargaon UHC. Thus, only 50% (95% CI: 37%-63%) of kala-azar cases were
      reported via the government passive surveillance system. Interviews with health
      staff based in the study UHC revealed the heavy reporting burden for multiple
      diseases, variation in staff experience, high demands on the staff time and
      considerable complexity in the recording system. After adjusting for kala-azar
      treatment drug, recording was found more likely for those aged 18 years or more,
      males, receiving supply and administration of drug at the UHC, and more recent
      treatment. DISCUSSION: Fifty percent of kala-azar cases occurring in one highly
      endemic area of Bangladesh were recorded in registers that were the source for
      monthly reports to the national surveillance system. Recording was influenced by
      patient, treatment, staff and system factors. Our findings have policy
      implications for the national surveillance system. Future studies involving
      larger samples and including interviews with health authorities at more central
      level and surveillance experts at the national level will generate more precise
      and representative evidence on the performance of kala-azar surveillance in
      Bangladesh.

PMID- 25860257
TI  - Apoptosis induced by Ginkgo biloba (EGb761) in melanoma cells is Mcl-1-dependent.
AB  - Melanoma is an aggressive skin cancer. Unfortunately, there is currently no
      chemotherapeutic agent available to significantly prolong the survival of the
      most patients with metastatic melanomas. Here we report that the Ginkgo biloba
      extract (EGb761), one of the most widely sold herbal supplements in the world,
      potently induces apoptosis in human melanoma cells by disturbing the balance
      between pro- and anti-apoptosis Bcl-2 family proteins. Treatment with EGb761
      induced varying degrees of apoptosis in melanoma cell lines but not in
      melanocytes. Induction of apoptosis was caspase-dependent and appeared to be
      mediated by the mitochondrial pathway, in that it was associated with reduction
      in mitochondrial membrane potential and activation of Bax and Bak. Although
      EGb761 did not cause significant change in the expression levels of the BH3-only
      Bcl-2 family proteins Bim, Puma, Noxa, and Bad, it significantly downregulated
      Mcl-1 in sensitive but not resistant melanoma cells, suggesting a major role of
      Mcl-1 in regulating apoptosis of melanoma cells induced by EGb761. Indeed, siRNA
      knockdown of Mcl-1 enhanced EGb761-induced apoptosis, which was associated with
      increased activation of Bax and Bak. Taken together, these results demonstrate
      that EGb761 kills melanoma cells through the mitochondrial apoptotic pathway, and
      that Mcl-1 is a major regulator of sensitivity of melanoma cells to apoptosis
      induced by EGb761. Therefore, EGb761 with or without in combination with
      targeting Mcl-1 may be a useful strategy in the treatment of melanoma. 

PMID- 25860259
TI  - Dopamine receptor and Galpha(olf) expression in DYT1 dystonia mouse models during
      postnatal development.
AB  - BACKGROUND: DYT1 dystonia is a heritable, early-onset generalized movement
      disorder caused by a GAG deletion (DeltaGAG) in the DYT1 gene. Neuroimaging
      studies and studies using mouse models suggest that DYT1 dystonia is associated
      with dopamine imbalance. However, whether dopamine imbalance is key to DYT1 or
      other forms of dystonia continues to be debated. METHODOLOGY/PRINCIPAL FINDINGS:
      We used Dyt1 knock out (Dyt1 KO), Dyt1 DeltaGAG knock-in (Dyt1 KI), and
      transgenic mice carrying one copy of the human DYT1 wild type allele (DYT1 hWT)
      or human DeltaGAG mutant allele (DYT1 hMT). D1R, D2R, and Galpha(olf) protein
      expression was analyzed by western blot in the frontal cortex, caudate-putamen
      and ventral midbrain in young adult (postnatal day 60; P60) male mice from all
      four lines; and in the frontal cortex and caudate putamen in juvenile (postnatal
      day 14; P14) male mice from the Dyt1 KI and KO lines. Dopamine receptor and
      Galpha(olf) protein expression were significantly decreased in multiple brain
      regions of Dyt1 KI and Dyt1 KO mice and not significantly altered in the DYT1 hMT
      or DYT1 hWT mice at P60. The only significant change at P14 was a decrease in D1R
      expression in the caudate-putamen of the Dyt1 KO mice. CONCLUSION/SIGNIFICANCE:
      We found significant decreases in key proteins in the dopaminergic system in
      multiple brain regions of Dyt1 KO and Dyt1 KI mouse lines at P60. Deletion of one
      copy of the Dyt1 gene (KO mice) produced the most pronounced effects. These data
      offer evidence that impaired dopamine receptor signaling may be an early and
      significant contributor to DYT1 dystonia pathophysiology.

PMID- 25860261
TI  - Identifying opportunities to increase HIV testing among mexican migrants: a call
      to step up efforts in health care and detention settings.
AB  - HIV testing and counseling is a critical component of HIV prevention efforts and
      core element of current "treatment as prevention" strategies. Mobility, low
      education and income, and limited access to health care put Latino migrants at
      higher risk for HIV and represent barriers for adequate levels of HIV testing in
      this population. We examined correlates of, and missed opportunities to increase,
      HIV testing for circular Mexican migrants in the U.S. We used data from a
      probability-based survey of returning Mexican migrants (N=1161) conducted in the
      border city of Tijuana, Mexico. We estimated last 12-months rates of HIV testing
      and the percentage of migrants who received other health care services or were
      detained in an immigration center, jail, or prison for 30 or more days in the
      U.S., but were not tested for HIV. Twenty-two percent of migrants received HIV
      testing in the last 12 months. In general, utilization of other health care
      services or detention for 30 or more days in the U.S. was a significant predictor
      of last 12-months HIV testing. Despite this association, we found evidence of
      missed opportunities to promote testing in healthcare and/or correctional or
      immigration detention centers. About 27.6% of migrants received other health care
      and/or were detained at least 30 days but not tested for HIV. Health care
      systems, jails and detention centers play an important role in increasing access
      to HIV testing among circular migrants, but there is room for improvement.
      Policies to offer opt-out, confidential HIV testing and counseling to Mexican
      migrants in these settings on a routine and ethical manner need to be designed
      and pilot tested. These policies could increase knowledge of HIV status,
      facilitate engagement in HIV treatment among a highly mobile population, and
      contribute to decrease incidence of HIV in the host and receiving communities. 

PMID- 25860263
TI  - [Adverse events associated with the treatment of inflammatory bowel disease].
AB  - BACKGROUND: The purpose of inflammatory bowel disease (IBD) treatment is to
      achieve resolution of symptoms and remission of disease with a minimum of adverse
      events (AE). AIM: To report AE of different prescriptions used for the treatment
      of IBD. MATERIAL AND METHODS: Analysis of a registry of patients with IBD held at
      a private clinic from 1976 to 2013. All used medications, the occurrence and
      severity of AE were recorded. RESULTS: The records of 346 patients aged 16 to 86
      years, 74% with ulcerative colitis, were analyzed. The most commonly type of
      medications prescribed were 5-aminosalicylates (5-ASAs) in 329 patients (92%),
      followed by adrenal steroids in 218 (61%). Forty nine AE were recorded in the
      same number of patents (14%). These were more common in patients with Crohn
      disease (n = 19, 21%). An univariate analysis, demonstrated that extra-intestinal
      manifestations, hospitalizations secondary to IBD crisis, requirement of surgery
      and treatment with steroids, immunosuppressants or biologic agents were
      significantly associated with the presence of AE. AEs were more common with
      immunosuppressants, followed by 5-ASAs and steroids. Discontinuation of therapy
      was required in 79, 100 and 43% of patients taking these medications,
      respectively. Twenty percent of AEs were severe. Leukopenia and pancytopenia
      along with alopecia were the most common AEs attributable to azathioprine.
      CONCLUSIONS: The occurrence of AEs in patients with IBD is uncommon. Even
      inmunosuppressants or biologic agents have a low rate of AE and most of them
      mild.

PMID- 25860264
TI  - [Cardiac adverse effects of domperidone in adult patients: a systematic review].
AB  - BACKGROUND: Domperidone is widely prescribed in patients with gastrointestinal
      disorders but some cardiac adverse effects have been recently reported. AIM: To
      evaluate the risk of QT prolongation, ventricular arrhythmias and sudden cardiac
      death associated with the use of oral domperidone in adults without cancer.
      MATERIAL AND METHODS: Systematic searches in MEDLINE, LILACS, SciELO, the
      Cochrane Library and regulatory agencies websites were performed, followed by a
      manual search of cited references. The search strategy consisted of combining
      free and indexed text words without any date or language restriction. RESULTS:
      Three case-control studies met the inclusion criteria; none of them evaluated QT
      interval prolongation. With low risk of bias, each study quantified the risk of
      ventricular arrhythmia or sudden cardiac death (VA/SCD). The odds ratios for
      these events in these studies were 4.7 (95% confidence interval (CI): 1.4-16),
      1.59 (95% CI: 1.28-1.98) and 11.02 (95% CI: 2.02-62.3) respectively. A
      significantly increased risk was observed in patients older than 60 years of age
      or receiving doses > 30 mg/day. CONCLUSIONS: Heterogeneity between selected
      studies did not allow the computation of a summary measure. However, evidence was
      found that an increased risk of VA/SCD is associated with the use of oral
      domperidone in adults.

PMID- 25860262
TI  - Tracheal dysplasia precedes bronchial dysplasia in mouse model of N-nitroso
      trischloroethylurea induced squamous cell lung cancer.
AB  - Squamous cell lung cancer (SCC) is the second leading cause of lung cancer death
      in the US and has a 5-year survival rate of only 16%. Histological changes in the
      bronchial epithelium termed dysplasia are precursors to invasive SCC. However,
      the cellular mechanisms that cause dysplasia are unknown. To fill this knowledge
      gap, we used topical application of N-nitroso-tris chloroethylurea (NTCU) for 32
      weeks to induce squamous dysplasia and SCC in mice. At 32 weeks the predominant
      cell type in the dysplastic airways was Keratin (K) 5 and K14 expressing basal
      cells. Notably, basal cells are extremely rare in the normal mouse bronchial
      epithelium but are abundant in the trachea. We therefore evaluated time-dependent
      changes in tracheal and bronchial histopathology after NTCU exposure (4, 8, 12,
      16, 25 and 32 weeks). We show that tracheal dysplasia occurs significantly
      earlier than that of the bronchial epithelium (12 weeks vs. 25 weeks). This was
      associated with increased numbers of K5+/K14+ tracheal basal cells and a complete
      loss of secretory (Club cell secretory protein expressing CCSP+) and ciliated
      cells. TUNEL staining of NTCU treated tissues confirmed that the loss of CCSP+
      and ciliated cells was not due to apoptosis. However, mitotic index (measured by
      bromodeoxyuridine incorporation) showed that NTCU treatment increased
      proliferation of K5+ basal cells in the trachea, and altered bronchial mitotic
      population from CCSP+ to K5+ basal cells. Thus, we demonstrate that NTCU-induced
      lung epithelial dysplasia starts in the tracheal epithelium, and is followed by
      basal cell metaplasia of the bronchial epithelium. This analysis extends our
      knowledge of the NTCU-SCC model by defining the early changes in epithelial cell
      phenotypes in distinct airway locations, and this may assist in identifying new
      targets for future chemoprevention studies. 

PMID- 25860266
TI  - [Primary care consultations due to respiratory diseases in the period 2003-2008].
AB  - BACKGROUND: Respiratory diseases are the third cause of death, and the second
      cause of hospitalization among people aged 65 years or more in Chile. AIM: To
      analyze the distribution of consultations due to respiratory diseases among
      adults living in Metropolitan Santiago. MATERIAL AND METHODS: A daily registry of
      all consultations of patients older than 15 years old in seven public primary
      care centers, was carried out between January 2003 and December 2008.
      Consultations were classified as having non-respiratory or respiratory causes.
      The latter were broke down in upper or lower respiratory diseases, pneumonia,
      chronic obstructive pulmonary disease (COPD) and asthma. RESULTS: A total of
      1,170,941 consultations were registered and 19% were due to respiratory diseases.
      Of these, 46% were due to upper respiratory diseases, 31% due to lower
      respiratory diseases, 8% due to COPD, 6% due to pneumonia, 5% due to asthma and
      4% due to other respiratory causes. Pneumonia and COPD were more frequent among
      consultants older than 65 years. CONCLUSIONS: Consultations due to respiratory
      diseases are approximately one fifth of all primary care consultations. Older
      people often have more chronic and severe diseases.

PMID- 25860265
TI  - [Positron emission tomography/computed tomography for lung cancer staging].
AB  - BACKGROUND: PET/CT (Positron Emission Tomography/Computed Tomography) is widely
      used in nodal and metastatic staging of lung cancer patients. AIM: To analyze
      PET/CT detection of metastatic disease in patients with lung cancer. MATERIAL AND
      METHODS: We reviewed retrospectively F18Fluorodeoxyglucose PET/CT scans performed
      between December 2008 and December 2013. We selected 143 patients aged 30 to 92
      years (63% males) with confirmed lung cancer referred for staging, with no
      previous treatment. We reviewed whole body PET/CT and brain magnetic resonance
      images. SUVmax (Standardized Uptake Value maximum) of primary pulmonary lesion,
      hilar/mediastinal nodes, and distant metastases were calculated. RESULTS:
      Histological types encountered were adenocarcinoma in 55%, squamous-cell in 15%,
      small-cell in 8%, large-cell in 6% and adeno-squamous in 2%. In 22 cases (15%)
      histology was not available. Nodal involvement was observed in 60% of patients
      (44% hilar and 48% mediastinal). Skip metastases (mediastinal involvement without
      hilum involvement) were encountered in 17% of cases, and were significantly more
      common among high uptake lung tumors (p < 0.01). Best SUVmax cut-off for node
      involvement was 4.4 for hilum and 4.0 for mediastinum (sensibility: 86.4%,
      specificity: 99.8%). Sixty six patients (46.2%) showed distant metastases on
      PET/CT. The most common metastases were osseous in 22%, adrenal in 16%, hepatic
      in14%, pulmonary in 14% and cerebral in 12%. PET/CT detected a second unexpected
      synchronic cancer in eight patients (6%). CONCLUSIONS: PET/CT is accurate for
      nodal staging using an uptake index as SUVmax. Distant metastases are common,
      especially in bone, adrenal glands and liver.

PMID- 25860260
TI  - Full-length human placental sFlt-1-e15a isoform induces distinct maternal
      phenotypes of preeclampsia in mice.
AB  - OBJECTIVE: Most anti-angiogenic preeclampsia models in rodents utilized the
      overexpression of a truncated soluble fms-like tyrosine kinase-1 (sFlt-1) not
      expressed in any species. Other limitations of mouse preeclampsia models included
      stressful blood pressure measurements and the lack of postpartum monitoring. We
      aimed to 1) develop a mouse model of preeclampsia by administering the most
      abundant human placental sFlt-1 isoform (hsFlt-1-e15a) in preeclampsia; 2)
      determine blood pressures in non-stressed conditions; and 3) develop a survival
      surgery that enables the collection of fetuses and placentas and postpartum (PP)
      monitoring. METHODS: Pregnancy status of CD-1 mice was evaluated with high
      frequency ultrasound on gestational days (GD) 6 and 7. Telemetry catheters were
      implanted in the carotid artery on GD7, and their positions were verified by
      ultrasound on GD13. Mice were injected through tail-vein with adenoviruses
      expressing hsFlt-1-e15a (n = 11) or green fluorescent protein (GFP; n = 9) on
      GD8/GD11. Placentas and pups were delivered by cesarean section on GD18 allowing
      PP monitoring. Urine samples were collected with cystocentesis on GD6/GD7, GD13,
      GD18, and PPD8, and albumin/creatinine ratios were determined. GFP and hsFlt-1
      e15a expression profiles were determined by qRT-PCR. Aortic ring assays were
      performed to assess the effect of hsFlt-1-e15a on endothelia. RESULTS: Ultrasound
      predicted pregnancy on GD7 in 97% of cases. Cesarean section survival rate was
      100%. Mean arterial blood pressure was higher in hsFlt-1-e15a-treated than in GFP
      treated mice (?MAP = 13.2 mmHg, p = 0.00107; GD18). Focal glomerular changes were
      found in hsFlt-1-e15a -treated mice, which had higher urine albumin/creatinine
      ratios than controls (109.3 +/- 51.7 MUg/mg vs. 19.3 +/- 5.6 MUg/mg, p = 4.4 x
      10(-2); GD18). Aortic ring assays showed a 46% lesser microvessel outgrowth in
      hsFlt-1-e15a-treated than in GFP-treated mice (p = 1.2 x 10(-2)). Placental and
      fetal weights did not differ between the groups. One mouse with liver disease
      developed early-onset preeclampsia-like symptoms with intrauterine growth
      restriction (IUGR). CONCLUSIONS: A mouse model of late-onset preeclampsia was
      developed with the overexpression of hsFlt-1-e15a, verifying the in vivo
      pathologic effects of this primate-specific, predominant placental sFlt-1
      isoform. HsFlt-1-e15a induced early-onset preeclampsia-like symptoms associated
      with IUGR in a mouse with a liver disease. Our findings support that hsFlt-1-e15a
      is central to the terminal pathway of preeclampsia, and it can induce the full
      spectrum of symptoms in this obstetrical syndrome.

PMID- 25860267
TI  - [Timed up and go right and left unipodal stance results in Chilean older people
      with different degrees of disability].
AB  - BACKGROUND: The Preventive Health Examination of older people in Chile
      incorporates the timed up and go (TUG) and right and left unipodal stance test
      (RUPS and LUPS) as functional assessment methods. AIM: To assess if TUG and LUPS
      discriminate older people with different degrees of disability. MATERIAL AND
      METHODS: TUG, RUPS and LUPS were assessed in 860 participants aged 71.3 +/- 6.9
      years (591 females) attending a primary health care clinic. The results of the
      three tests were expressed in seconds. Participants were classified as non
      disabled without any risk, non-disabled with risk and in risk of dependence,
      using the Functional Assessment of Older People of EFAM (the Spanish acronym),
      previously validated for Chilean older people. RESULTS: In all participants TUG,
      LUPS and RUPS values were 8.9 +/- 3.6, 10 +/- 10.6 and 9.7 +/- 10.3 seconds (sec)
      respectively. Among non-disabled participants without risk, the values for TUG,
      RUPS and LUPS were: 7.9 +/- 2.3, 12.7 +/- 11.1 and 12.2 +/- 10.9 sec
      respectively. The figures for non-disabled participants with risk were 8.4 +/-
      2.6, 8.8 +/- 9.8 and 8.9 +/- 9.8 sec respectively. The figures for participants
      in risk of dependence were 11.7 +/- 5.3, 5.1 +/- 7.8 and 4.5 +/- 7.1 sec,
      respectively. CONCLUSIONS: In this group of older participants there is an
      association between the degree of disability and the results of TUG, RUPS and
      LUPS.

PMID- 25860268
TI  - [Psychosocial stress among health care workers].
AB  - BACKGROUND: Health care workers are exposed to high stress levels and
      psychosocial risks. The imbalance between the invested efforts and received
      rewards acquires special importance in this setting. AIM: To assess the
      psychosocial risk level and its relationship with depression, distress and
      psychotropic drug use among health care workers. MATERIAL AND METHODS: Seven
      hundred eighty two workers (602 females; 180 males) answered self-administered
      questionnaires to measure psychosocial risk and mental health. RESULTS: Twenty
      five percent of respondents used psychotropic drugs, 34% had a high level of
      distress and 23% had depressive symptoms. They also reported a low level of
      decisional latitude (48%), high emotional demands (47%), low social support (41%)
      and a significant effort-reward imbalance (67%). Those exposed to job strain
      (high demands and low decisional latitude), iso-strain (job strain plus low
      social support), and effort-reward imbalance were twice as likely to suffer
      symptoms of depression and elevated distress compared to non-exposed subjects.
      CONCLUSIONS: There are high levels of psychosocial stress among health care
      workers.

PMID- 25860269
TI  - [Human papillomavirus testing in cervical cancer screening at a public health
      service of Santiago, Chile].
AB  - BACKGROUND: Molecular techniques for human papillomavirus (HPV) detection have a
      good performance as screening tests and could be included in cervical cancer
      early detection programs. We conducted a population-based trial comparing HPV
      detection and Papanicolaou as primary screening tests, in a public health service
      in Santiago, Chile. AIM: To describe the experience of implementing this new
      molecular test and present the main results of the study. MATERIAL AND METHODS:
      Women aged 25 to 64 enrolled in three public health centers were invited to
      participate. In all women, samples were collected for Papanicolaou and HPV DNA
      testing, and naked-eye visual inspection of the cervix with acetic acid was
      performed. Women with any positive screening test were referred to the local area
      hospital for diagnostic confirmation with colposcopy and biopsy of suspicious
      lesions. RESULTS: Screening results were obtained for 8265 women, of whom 931
      (11.3%) were positive to any test. The prevalence of cervical intraepithelial
      neoplasia grade 2 or worse (CIN2+) was 1.1%; nine women had invasive cervical
      cancer. Sensitivities for the detection of CIN2+ were 22.1% (95% confidence
      interval (CI) 16.4-29.2) for Papanicolaou and 92.7% (95% CI 84.4-96.8) for HPV
      testing; specificities were 98.9% (95% CI 98.7-99.0) and 92.0% (95% CI 91.4-92.6)
      respectively. CONCLUSION: This experience showed that the implementation of a
      molecular test for cervical cancer screening is not a major challenge in Chile:
      it was well accepted by both the health team and the participants, and it may
      improve the effectiveness of the screening program.

PMID- 25860270
TI  - [Safety and efficacy of Vildagliptin in real life Chilean diabetic patients].
AB  - BACKGROUND: Vildagliptin is a dipeptidyl peptidase IV inhibitor (DPP4i). Its
      efficacy and safety of DPP4i in Chilean real life type 2 diabetic (T2D) patients
      is not well known. AIM: To assess the safety profile and effectiveness of 12
      weeks of treatment with Vildagliptin for glycemic control in T2D Chilean patients
      with a poor glycemic control. PATIENTS AND METHODS: Retrospective assessment of
      the effects of Vildagliptin treatment during 12 weeks in 103 T2D patients aged 29
      to 92 years (47% males). The main outcomes were changes in glycosylated
      hemoglobin and the occurrence of adverse effects. RESULTS: After 12 weeks of
      Vildagliptin use, glycosylated hemoglobin decreased from 8.3 +/- 1.4 to 7.2 +/-
      1.1% (p < 0.01). Fasting plasma glucose and the number of hypoglycemic events
      also decreased significantly. No significant weight change was observed. The
      treatment had good compliance, tolerance and patient satisfaction. CONCLUSIONS:
      Vildagliptin treatment reduced glycosylated hemoglobin by 1.1% and was well
      tolerated in this group of diabetic patients.

PMID- 25860271
TI  - [Comparison of the use of isoproterenol or nitroglycerine during the Tilt test].
AB  - BACKGROUND: There is debate about the advantages of different protocols
      usefulness of tilt test for the diagnosis of vasovagal collapse. AIM: To compare
      the sensitivity, specificity, adverse reactions, complications and time
      requirements of two different Tilt test protocols. MATERIAL AND METHODS: A Tilt
      test using isoproterenol in progressive doses (2 MUg for 10 min and 5 MUg for 5
      min posteriorly was performed in 159 patients aged 9 to 84 years (59 males).
      Another Tilt test using sublingual nitroglycerine in doses of 0.3 mg was
      performed in 201 patients aged 8 to 87 years (62 males). Also, 20 healthy
      volunteers were tested. RESULTS: The positivity rates of the tests using
      isoproterenol and nitroglycerin were 75.5 and 77.6% respectively (NS). The
      figures for sensitivity were 98.4 and 99.3% (NS). The figures for specificity
      were 93.2 and 98.4% (NS). The test using isoproterenol requires 15 more minutes.
      As adverse reactions, 38% of participants experienced palpitations with
      isoproterenol and 22% experienced headache with nitroglycerin. CONCLUSIONS: The
      Tilt test with nitroglycerin is shorter, simpler, painless, with less personnel
      involved and has the same diagnostic accuracy than the test with isoproterenol.

PMID- 25860272
TI  - [Association between obesity and chronic renal disease].
AB  - A higher frequency of chronic renal disease is observed in obese patients,
      suggesting a pathogenic association between both conditions. Obesity unmasks
      clinical manifestations of chronic kidney disease such as high blood pressure,
      which may accelerate its progression. Obesity also promotes hyper filtration and
      the appearance of microalbuminuria, activates the renin-angiotensin-aldosterone
      system and is associated with high levels of pro-inflammatory cytokines.
      Therefore weight reduction may slow the progression of chronic renal disease and
      reduce its associated cardiovascular risk factors. 

PMID- 25860273
TI  - [Return to work enablers for workers with work-related mental illness].
AB  - BACKGROUND: There is growing interest in the treatment and return-to-work of
      workers with labor related mental illnesses. AIM: To perform a systematic review
      of practices and interventions that improve return to work. MATERIAL AND METHODS:
      Systematic literature review. Thirty articles were selected for in- depth
      analysis. RESULTS: Self efficacy perception, work motivation, a lower age and a
      better socioeconomic status were identified as worker-related return to work
      facilitators. Among work environment facilitators, good communication practices,
      supervisor support, a good assessment and modification of work load, adjustment
      of expectations, a good relationship between employers and employees and positive
      work experiences were identified. Treatment may improve return to work using a
      multidisciplinary approach, reducing stress and identifying psychosocial
      determinants of mental problems rather than symptoms and providing a timely
      health care. CONCLUSIONS: Return to work of workers with labor related mental
      illnesses requires a constant sharing of information between health care workers,
      employers and employees to identify common therapeutic objectives.

PMID- 25860274
TI  - [Considerations on the new Chilean law about rights and duties of patients].
AB  - After years of discussion by the Chilean legislature, the Law No 20.584, which
      regulates health care related rights and duties of people, entered into force in
      Chile in October 2012. This bill represents an important step in the recognition
      and protection of health care related rights, welfare, dignity and duties of
      persons. It also intends to protect potential participants in clinical research.
      However such protective measures include explicit prohibitions such as the review
      of clinical records or the inclusion of people with mental or psychological
      handicaps as research participants. We herein discuss the implications of this
      law in medical research. 

PMID- 25860275
TI  - [ProfessorHernan Alessandri, M.D. (1900-1980)].
AB  - Hernan Alessandri M.D. was an outstanding clinician and a leading medical
      educator, born in Santiago in 1900 where he died in 1980 [corrected]. He received
      his medical degree at the University of Chile in 1923, became Professor of
      Clinical Medicine in 1932, Full Professor and Chair of Internal Medicine in 1944.
      At the Hospital del Salvador, in Santiago, he chaired a teaching Department and a
      Clinical Service that was an example for its academic environment and dedication
      to patients and students. From 1958 to 1962 he was Dean of the University of
      Chile Faculty of Medicine, conducting a reform of teaching curricula and
      organizing medical residency programs for the training of specialists, originally
      started in his own Service in 1952. The American College of Physicians awarded
      him the first foreign Honorary Membership. He was a founding Member of the
      Chilean Academy of Medicine (1964). In 1973 the University of Chile awarded him
      the Emeritus Professor status. He was considered by his peers, alumni and
      patients a brilliant clinician and an exceptional medical educator. Since 1980 a
      Social and Teaching Foundation bears his name and in 2014, with the occasion of
      the XXXV Chilean Congress of Internal Medicine, the Sociedad Medica de Santiago
      Chilean Society of Internal Medicine created an annual lecture to render tribute
      to distinguished physicians and his name was one of the two selected to
      inaugurate them.

PMID- 25860276
TI  - [Professor Hernan Alessandri, M.D.: his legacy for the new generations of
      physicians].
AB  - Professor Alessandri died in 1980. We started our residency in Internal Medicine
      about 30 years later. Considering the profound changes our society has witnessed,
      including medical practice, I would like to approach the meaning of his work for
      our generation. It is not the Father's figure nor his Aura what inspires us
      today. Neither is his personality nor his shape. His universality comes from his
      transcendent image as a teacher. Today's teachers live rough times, their social
      status has changed, their professional requirements have grown exponentially,
      they have to adapt to social phenomena like the Internet and multiculturalism.
      Being a teacher nowadays demands to be a multifaceted expert. Things have changed
      since Professor Alessandri made rounds with his patients. But a deeper look
      allows us to understand that everything returns to where it started: professional
      deontology of the teacher, never fading but transcendent. We know that Doctor
      Alessandri had the natural gift to keep faithful to that code with consistency
      and perseverance. He excelled with integrity in every aspect including
      professional betterment, constructive work for his institution, collegiality, a
      warm relationship with students and a model of social values. Beyond virtues and
      personal defects he will keep on being the mould in which present teachers should
      be formed, engraved in their souls and in the subconscious of students that seek
      to learn. 

PMID- 25860277
TI  - [Cystic degeneration of the popliteal artery: Report of one case].
AB  - Cystic degeneration of the popliteal artery is an uncommon cause of intermittent
      claudication. We report a 52 years old male consulting for intermittent
      claudication referred to the calf. The angiography showed a 93% stenosis in
      segment of 45 mm length of the left popliteal artery with a smooth surface,
      suggesting an extrinsic compression. A CT angiography of the lower limb suggested
      the presence of a cystic degeneration. The patient was operated and the middle
      third of the popliteal artery was excised. The pathological study of the surgical
      piece was informed as artery media cystic degeneration. 

PMID- 25860278
TI  - [Changes in the pattern of substance use after bariatric surgery: report of one
      case].
AB  - Even though the benefits of bariatric surgery are supported by scientific
      evidence, its indications and contraindications must be revised to avoid its
      indiscriminate use. Substance use is more common in patients subjected to
      bariatric surgery than in the general population. After surgery, an increase in
      alcohol abuse has been reported. We report a 41 years old male, with morbid
      obesity, alcohol and cocaine use. After bariatric surgery, his alcohol tolerance
      significantly decreased, increasing the doses of cocaine and starting to consume
      it without alcohol. His high anxiety level and paranoid delusions, motivated him
      to seek help in a rehabilitation center where a Substance Dependence Disorder was
      diagnosed and received initial treatment. The cause of this adverse effect needs
      further research. Functional and anatomic changes in the digestive tract lead to
      a greater alcohol absorption and reduced alcohol dehydrogenase activity. Also
      neurochemical alterations may produce a displacement from compulsive use of food
      to compulsive use of addictive substances. 

PMID- 25860279
TI  - [Pneumomediastinum and cutaneous necrosis in dermatomyositis: Report of one
      case].
AB  - We report a 37 years old male with a dermatomyositis treated with oral
      cyclophosphamide. He was admitted to the hospital due to a zone of skin necrosis
      with purulent exudate, located in the second left toe. A complete blood count
      showed a leukocyte count of 2,600 cells/mm3. A Chest CAT scan showed a
      pneumomediastinum with emphysema of adjacent soft tissue. Cyclophosphamide was
      discontinued and leukocyte count improved. The affected toe was amputated and a
      chest CAT scan showed a partial resolution of the pneumomediastinum. We discuss
      and review the pathogenesis, clinical presentation and management of
      pneumomediastinum and cutaneous necrosis in association with dermatomyositis. 

PMID- 25860281
TI  - [Diagnosis of Spinocerebellar Ataxia type 3 (Machado-Joseph disease) in Chile].

PMID- 25860282
TI  - [Translational research in Health topics: A road for pragmatic and
      interdisciplinary research].

PMID- 25860283
TI  - [Pyoderma gangrenosum: excellent response to topical therapy].

PMID- 25860284
TI  - Combination of erlotinib and EGCG induces apoptosis of head and neck cancers
      through posttranscriptional regulation of Bim and Bcl-2.
AB  - Combinatorial approaches using two or more compounds are gaining increasing
      attention for cancer therapy. We have previously reported that the combination of
      the EGFR-TKI erlotinib and epigallocatechin-3-gallate (EGCG) exhibited
      synergistic chemopreventive effects in head and neck cancers by inducing the
      expression of Bim, p21, p27, and by inhibiting the phosphorylation of ERK and AKT
      and expression of Bcl-2. In the current study, we further investigated the
      mechanism of regulation of Bim, Bcl-2, p21 and p27, and their role in apoptosis.
      shRNA-mediated silencing of Bim significantly inhibited apoptosis induced by the
      combination of erlotinib and EGCG (p = 0.005). On the other hand, overexpression
      of Bcl-2 markedly protected cells from apoptosis (p = 0.003), whereas
      overexpression of constitutively active AKT only minimally protected cells from
      apoptosis induced by the combination of the two compounds. Analysis of mRNA
      expression by RT-PCR revealed that erlotinib, EGCG and their combination had no
      significant effects on the mRNA expression of Bim, p21, p27 or Bcl-2 suggesting
      the post-transcriptional regulation of these molecules. Furthermore, we found
      that erlotinib or the combination of EGCG and erlotinib inhibited the
      phosphorylation of Bim and stabilized Bim after inhibition of protein translation
      by cycloheximide. Taken together, our results strongly suggest that the
      combination of erlotinib and EGCG induces apoptosis of SCCHN cells by regulating
      Bim and Bcl-2 at the posttranscriptional level. 

PMID- 25860285
TI  - Differentiation between solid-ankle cushioned heel and energy storage and return
      prosthetic foot based on step-to-step transition cost.
AB  - Decreased push-off power by the prosthetic foot and inadequate roll-over shape of
      the foot have been shown to increase the energy dissipated during the step-to
      step transition in human walking. The aim of this study was to determine whether
      energy storage and return (ESAR) feet are able to reduce the mechanical energy
      dissipated during the step-to-step transition. Fifteen males with a unilateral
      lower-limb amputation walked with their prescribed ESAR foot (Vari-Flex, Ossur;
      Reykjavik, Iceland) and with a solid-ankle cushioned heel foot (SACH) (1D10,
      Ottobock; Duderstadt, Germany), while ground reaction forces and kinematics were
      recorded. The positive mechanical work on the center of mass performed by the
      trailing prosthetic limb was larger (33%, p = 0.01) and the negative work
      performed by the leading intact limb was lower (13%, p = 0.04) when walking with
      the ESAR foot compared with the SACH foot. The reduced step-to-step transition
      cost coincided with a higher mechanical push-off power generated by the ESAR foot
      and an extended forward progression of the center of pressure under the
      prosthetic ESAR foot. Results can explain the proposed improvement in walking
      economy with this kind of energy storing and return prosthetic foot. 

PMID- 25860286
TI  - Thrombomodulin contributes to gamma tocotrienol-mediated lethality protection and
      hematopoietic cell recovery in irradiated mice.
AB  - Systemic administration of recombinant thrombomodulin (TM) confers radiation
      protection partly by accelerating hematopoietic recovery. The uniquely potent
      radioprotector gamma tocotrienol (GT3), in addition to being a strong
      antioxidant, inhibits the enzyme hydroxy-methyl-glutaryl-coenzyme A reductase
      (HMGCR) and thereby likely modulates the expression of TM. We hypothesized that
      the mechanism underlying the exceptional radioprotective properties of GT3 partly
      depends on the presence of endothelial TM. In vitro studies confirmed that
      ionizing radiation suppresses endothelial TM (about 40% at 4 hr after 5 Gy gamma
      irradiation) and that GT3 induces TM expression (about 2 fold at the mRNA level
      after 5 MUM GT3 treatment for 4 hr). In vivo survival studies showed that GT3 was
      significantly more effective as a radioprotector in TM wild type (TM+/+) mice
      than in mice with low TM function (TMPro/-). After exposure to 9 Gy TBI, GT3 pre
      treatment conferred 85% survival in TM+/+ mice compared to only 50% in TMPro/-.
      Thus, GT3-mediated radiation lethality protection is partly dependent on
      endothelial TM. Significant post-TBI recovery of hematopoietic cells,
      particularly leukocytes, was observed in TM+/+ mice (p = 0.003), but not in
      TMPro/- mice, despite the fact that GT3 induced higher levels of granulocyte
      colony stimulating factor (G-CSF) in TMPro/- mice (p = 0.0001). These data
      demonstrate a critical, G-CSF-independent, role for endothelial TM in GT3
      mediated lethality protection and hematopoietic recovery after exposure to TBI
      and may point to new strategies to enhance the efficacy of current medical
      countermeasures in radiological/nuclear emergencies. 

PMID- 25860288
TI  - Opportunistic infections and immune reconstitution inflammatory syndrome in HIV-1
      infected adults in the combined antiretroviral therapy era: a comprehensive
      review.
AB  - Despite the availability of effective combined antiretroviral treatment, many
      patients still present with advanced HIV infection, often accompanied by an AIDS
      defining disease. A subgroup of patients starting antiretroviral treatment under
      these clinical conditions may experience paradoxical worsening of their disease
      as a result of an exaggerated immune response towards an active (but also
      subclinical) infectious agent, despite an appropriate virological and
      immunological response to the treatment. This clinical condition, known as immune
      reconstitution inflammatory syndrome, may cause significant morbidity and even
      mortality if it is not promptly recognized and treated. This review updates
      current knowledge about the incidence, diagnostic criteria, risk factors,
      clinical manifestations, and management of opportunistic infections and immune
      reconstitution inflammatory syndrome in the combined antiretroviral treatment
      era. 

PMID- 25860287
TI  - High expression of c-kit mRNA predicts unfavorable outcome in adult patients with
      t(8;21) acute myeloid leukemia.
AB  - The reason that a certain subgroup of acute myeloid leukemia (AML) patients with
      t(8;21) translocation (generating the AML1/ETO fusion gene) displays a poor
      survival remains elusive. The proto-oncogene c-kit is expressed in approximately
      80% of AML cases. The kinase domain mutation of the c-kit gene, one of the most
      common gain-of-function mutations associated with t(8;21) AML, predicts higher
      relapse risk and poor prognosis. However, the role of c-kit high expression in
      t(8;21) AML remains poorly understood. Here we evaluated the prognostic
      significance of c-kit expression levels in AML patients. The mRNA expression of c
      kit was determined by real-time quantitative reverse transcription PCR in 132
      adult AML patients. Patients were grouped into quartiles according to c-kit
      expression levels (Q1-Q4, each quartile containing 25% of patients) and divided
      into c-kit high (Q4; n = 33) and c-kit low (Q1-Q3; n = 99). High c-kit expression
      was associated with AML1/ETO-positive and with c-kit mutation. Of note, 35.8% of
      the AML1/ETO-positive AML patients carrying wild-type c-kit expressed high levels
      of c-kit, suggesting that other factors are involved in c-kit overexpression.
      High c-kit expression was associated with inferior overall and event-free
      survival in AML1/ETO-positive patients and was independently predictive for
      overall and event-free survival in multivariate analyses in a c-kit mutation
      independent manner. Thus, high c-kit expression serves as a reliable molecular
      marker for poor prognosis, supporting a pathogenetic role of c-kit signaling in
      AML1/ETO-positive AML. AML1/ETO-positive patients with high c-kit expression
      might benefit from early treatment modifications and molecular target therapies. 

PMID- 25860289
TI  - Characterizing the transmission potential of zoonotic infections from minor
      outbreaks.
AB  - The transmission potential of a novel infection depends on both the inherent
      transmissibility of a pathogen, and the level of susceptibility in the host
      population. However, distinguishing between these pathogen- and population
      specific properties typically requires detailed serological studies, which are
      rarely available in the early stages of an outbreak. Using a simple transmission
      model that incorporates age-stratified social mixing patterns, we present a novel
      method for characterizing the transmission potential of subcritical infections,
      which have effective reproduction number R<1, from readily available data on the
      size of outbreaks. We show that the model can identify the extent to which
      outbreaks are driven by inherent pathogen transmissibility and pre-existing
      population immunity, and can generate unbiased estimates of the effective
      reproduction number. Applying the method to real-life infections, we obtained
      accurate estimates for the degree of age-specific immunity against monkeypox,
      influenza A(H5N1) and A(H7N9), and refined existing estimates of the reproduction
      number. Our results also suggest minimal pre-existing immunity to MERS-CoV in
      humans. The approach we describe can therefore provide crucial information about
      novel infections before serological surveys and other detailed analyses are
      available. The methods would also be applicable to data stratified by factors
      such as profession or location, which would make it possible to measure the
      transmission potential of emerging infections in a wide range of settings. 

PMID- 25860290
TI  - Membrane Curvature Affects the Formation of alpha-Hemolysin Nanopores.
AB  - Membrane proteins perform their functions within or on the lipid membrane, and
      lipid compositions are known to affect membrane protein integration and activity.
      Recently, the geometric aspect of membrane curvature was shown to play an
      important role in membrane protein behavior. Certain membrane proteins are known
      to sense the curvature of the membrane and to preferentially bind to highly
      curved membranes. However, although numerous membrane proteins assemble to form
      homo- or heterocomplexes and perform their biological functions, the dependence
      of membrane protein assembly on membrane curvature remains elusive. In this
      study, we analyzed the effect of the membrane curvature on the nanopore formation
      of alpha-hemolysin (AH), which is a toxic membrane protein derived from
      Staphylococcus aureus. The AH protein binds to the membrane as a monomer,
      assembles to form a heptamer, and forms a nanopore. By simultaneously measuring
      the molecules bound to the membrane and the activities of the nanopore on the
      membrane, we determined the nanopore formation ratio of AH. We used various sizes
      of liposomes and analyzed the dependence on the membrane curvature by using flow
      cytometry. Combining the results for positive and negative curvature, we found
      that the nanopore formation ratio of AH was curvature sensitive and was higher in
      a flat membrane than in a curved membrane. Furthermore, the nanopore formation
      ratio was almost identical or relatively higher in membranes with negative
      curvature than those with positive curvature.

PMID- 25860291
TI  - Sorafenib improves rituximab and ofatumumab efficacy by decreasing the expression
      of complement regulatory proteins.

PMID- 25860292
TI  - Identification of SUPT3H as a novel 8q24/MYC partner in blastic plasmacytoid
      dendritic cell neoplasm with t(6;8)(p21;q24) translocation.

PMID- 25860293
TI  - Mesenchymal stromal cells derived from acute myeloid leukemia bone marrow exhibit
      aberrant cytogenetics and cytokine elaboration.
AB  - Bone marrow-derived mesenchymal stromal cells (BM-MSCs) play a fundamental role
      in the BM microenvironment (BME) and abnormalities of these cells may contribute
      to acute myeloid leukemia (AML) pathogenesis. The aim of the study was to
      characterize the cytokine and gene expression profile, immunophenotype and
      cytogenetics of BM-MSCs from AML patients compared to normal BM-MSCs from healthy
      donors. AML BM-MSCs showed decreased monocyte chemoattractant protein-1 levels
      compared to normal BM-MSCs. AML BM-MSCs expressed similar beta1 integrin, CD44,
      CD73, CD90 and E-cadherin compared to normal BM-MSCs. Cytogenetic analysis
      revealed chromosomal aberrations in AML BM-MSCs, some overlapping with and others
      distinct from their corresponding AML blasts. No significant difference in gene
      expression was detected between AML BM-MSCs compared to normal BM-MSCs; however,
      comparing the differences between AML and MSCs from AML patients with the
      differences between normal hematopoietic cells and normal MSCs by Ingenuity
      pathway analysis showed key distinctions of the AML setting: (1) upstream gene
      regulation by transforming growth factor beta 1, tumor necrosis factor, tissue
      transglutaminase 2, CCAAT/enhancer binding protein alpha and SWItch/Sucrose
      NonFermentable related, matrix associated, actin dependent regulator of
      chromatin, subfamily a, member 4; (2) integrin and interleukin 8 signaling as
      overrepresented canonical pathways; and (3) upregulation of transcription factors
      FBJ murine osteosarcoma viral oncogene homolog and v-myb avian myeloblastosis
      viral oncogene homolog. Thus, phenotypic abnormalities of AML BM-MSCs highlight a
      dysfunctional BME that may impact AML survival and proliferation. 

PMID- 25860295
TI  - Analysis of the binding of bovine and human fibrinogen to ferritin: evidence that
      fibrinogen is a common ferritin-binding protein in mammals.
AB  - Both human and horse fibrinogen are heme-binding proteins, and horse fibrinogen
      also exhibits heme-mediated ferritin binding. This study found that bovine and
      human fibrinogen are heme-mediated ferritin-binding proteins and demonstrated
      direct binding of bovine ferritin to protoporphyrin (PPIX) and its derivatives or
      to Zn ions. Binding of bovine and human fibrinogen to bovine spleen ferritin
      coated on microtiter plate wells was detected using an anti-human fibrinogen
      antibody, and this binding was inhibited in a dose-dependent manner by hemin
      (iron-PPIX) and also inhibited by Zn-PPIX. PPIX showed less of an inhibitory
      effect on the binding of bovine and human fibrinogen to bovine ferritin. The
      inhibitory effect of Sn-PPIX was similar to that of PPIX, but with respect to
      human fibrinogen, PPIX did not inhibit the binding of human fibrinogen to
      ferritin. Bovine fibrinogen immobilized on CNBr-activated Sepharose 4B beads
      showed affinity for hemin, Sn-PPIX, Zn-PPIX, and iron-free PPIX in the order Sn
      PPIX < iron-free PPIX < hemin < Zn-PPIX. The fibrinogen beads also directly bound
      to zinc ions. These results suggest that bovine fibrinogen is a heme- and zinc
      binding protein and that binding of circulating mammalian fibrinogen to ferritin
      is heme mediated.

PMID- 25860294
TI  - Genetic and epigenetic profiling of CLL disease progression reveals limited
      somatic evolution and suggests a relationship to memory-cell development.
AB  - We examined genetic and epigenetic changes that occur during disease progression
      from indolent to aggressive forms of chronic lymphocytic leukemia (CLL) using
      serial samples from 27 patients. Analysis of DNA mutations grouped the leukemia
      cases into three categories: evolving (26%), expanding (26%) and static (47%).
      Thus, approximately three-quarters of the CLL cases had little to no genetic
      subclonal evolution. However, we identified significant recurrent DNA methylation
      changes during progression at 4752 CpGs enriched for regions near Polycomb 2
      repressive complex (PRC2) targets. Progression-associated CpGs near the PRC2
      targets undergo methylation changes in the same direction during disease
      progression as during normal development from naive to memory B cells. Our study
      shows that CLL progression does not typically occur via subclonal evolution, but
      that certain CpG sites undergo recurrent methylation changes. Our results suggest
      CLL progression may involve developmental processes shared in common with the
      generation of normal memory B cells.

PMID- 25860296
TI  - Diastereoselective Synthesis of 1-Deoxygalactonojirimycin, 1
      Deoxyaltronojirimycin, and N-Boc-(2S,3S)-3-Hydroxypipecolic Acid via Proline
      Catalyzed alpha-Aminoxylation of Aldehydes.
AB  - An efficient synthesis of deoxygalactonojirimycin and deoxyaltronojirimycin
      through the use of proline catalyzed asymmetric alpha-aminoxylation of a higher
      homologue of Garner's aldehyde, derived from l-aspartic acid, is reported. The
      method is also used for a highly diastereoselective synthesis of the N-Boc
      derivative of (2S,3S)-3-hydroxypipecolic acid. The configuration of the proline
      catalyst used for the asymmetric aminoxylation step ultimately controls the
      absolute configuration of three adjacent stereogenic centers in the final
      products. 

PMID- 25860297
TI  - Circulating miRNAs as potential biomarkers of therapy effectiveness in rheumatoid
      arthritis patients treated with anti-TNFalpha.
AB  - INTRODUCTION: The advent of anti-tumor necrosis factor alpha (anti-TNFalpha)
      drugs has considerably improved medical management in rheumatoid arthritis (RA)
      patients, although it has been reported to be ineffective in a fraction of them.
      MicroRNAs (miRNAs) are small, non-coding RNAs that act as fine-tuning regulators
      of gene expression. Targeting miRNAs by gain or loss of function approaches have
      brought therapeutic effects in various disease models. The aim of this study was
      to investigate serum miRNA levels as predictive biomarkers of response to anti
      TNFalpha therapy in RA patients. METHODS: In total, 95 RA patients undergoing
      anti-TNFalpha/disease-modifying antirheumatic drugs (anti-TNFalpha/DMARDs)
      combined treatments were enrolled. Serum samples were obtained at 0 and 6 months
      and therapeutic efficacy was assessed. miRNAs were isolated from the serum of 10
      patients before and after anti-TNFalpha/DMARDs combination therapy, cDNA
      transcribed and pooled, and human serum miRNA polymerase chain reaction (PCR)
      arrays were performed. Subsequently, selected miRNAs were analyzed in a
      validation cohort consisting of 85 RA patients. Correlation studies with clinical
      and serological variables were also performed. RESULTS: Ninety percent of RA
      patients responded to anti-TNFalpha/DMARDs combination therapy according to
      European League Against Rheumatism (EULAR) criteria. Array analysis showed that
      91% of miRNAS were overexpressed and 9% downregulated after therapy. Functional
      classification revealed a preponderance of target mRNAs involved in reduction of
      cells maturation--especially on chondrocytes--as well as in immune and
      inflammatory response, cardiovascular disease, connective tissue and
      musculoskeletal system. Six out of ten miRNAs selected for validation were found
      significantly upregulated by anti-TNFalpha/DMARDs combination therapy (miR-16-5p,
      miR-23-3p, miR125b-5p, miR-126-3p, miRN-146a-5p, miR-223-3p). Only responder
      patients showed an increase in those miRNAs after therapy, and paralleled the
      reduction of TNFalpha, interleukin (IL)-6, IL-17, rheumatoid factor (RF), and C
      reactive protein (CRP). Correlation studies demonstrated associations between
      validated miRNAs and clinical and inflammatory parameters. Further, we identified
      a specific plasma miRNA signature (miR-23 and miR-223) that may serve both as
      predictor and biomarker of response to anti-TNFalpha/DMARDs combination therapy.
      CONCLUSIONS: miRNA levels in the serum of RA patients before and after anti
      TNFalpha/DMARDs combination therapy are potential novel biomarkers for predicting
      and monitoring therapy outcome.

PMID- 25860298
TI  - Global burden of invasive nontyphoidal Salmonella disease, 2010(1).
AB  - Nontyphoidal Salmonella is a major cause of bloodstream infections worldwide, and
      HIV-infected persons and malaria-infected children are at increased risk for the
      disease. We conducted a systematic literature review to obtain age group
      specific, population-based invasive nontyphoidal Salmonella (iNTS) incidence
      data. Data were categorized by HIV and malaria prevalence and then extrapolated
      by using 2010 population data. The case-fatality ratio (CFR) was determined by
      expert opinion consensus. We estimated that 3.4 (range 2.1-6.5) million cases of
      iNTS disease occur annually (overall incidence 49 cases [range 30-94] per 100,000
      population). Africa, where infants, young children, and young adults are most
      affected, has the highest incidence (227 cases [range 152-341] per 100,000
      population) and number of cases (1.9 [range 1.3-2.9] million cases). An iNTS CFR
      of 20% yielded 681,316 (range 415,164-1,301,520) deaths annually. iNTS disease is
      a major cause of illness and death globally, particularly in Africa. Improved
      understanding of the epidemiology of iNTS is needed. 

PMID- 25860299
TI  - A practical cone-beam CT scatter correction method with optimized Monte Carlo
      simulations for image-guided radiation therapy.
AB  - Cone-beam CT (CBCT) has become the standard image guidance tool for patient setup
      in image-guided radiation therapy. However, due to its large illumination field,
      scattered photons severely degrade its image quality. While kernel-based scatter
      correction methods have been used routinely in the clinic, it is still desirable
      to develop Monte Carlo (MC) simulation-based methods due to their accuracy.
      However, the high computational burden of the MC method has prevented routine
      clinical application. This paper reports our recent development of a practical
      method of MC-based scatter estimation and removal for CBCT. In contrast with
      conventional MC approaches that estimate scatter signals using a scatter
      contaminated CBCT image, our method used a planning CT image for MC simulation,
      which has the advantages of accurate image intensity and absence of image
      truncation. In our method, the planning CT was first rigidly registered with the
      CBCT. Scatter signals were then estimated via MC simulation. After scatter
      signals were removed from the raw CBCT projections, a corrected CBCT image was
      reconstructed. The entire workflow was implemented on a GPU platform for high
      computational efficiency. Strategies such as projection denoising, CT image
      downsampling, and interpolation along the angular direction were employed to
      further enhance the calculation speed. We studied the impact of key parameters in
      the workflow on the resulting accuracy and efficiency, based on which the optimal
      parameter values were determined. Our method was evaluated in numerical
      simulation, phantom, and real patient cases. In the simulation cases, our method
      reduced mean HU errors from 44 to 3 HU and from 78 to 9 HU in the full-fan and
      the half-fan cases, respectively. In both the phantom and the patient cases,
      image artifacts caused by scatter, such as ring artifacts around the bowtie area,
      were reduced. With all the techniques employed, we achieved computation time of
      less than 30 s including the time for both the scatter estimation and CBCT
      reconstruction steps. The efficacy of our method and its high computational
      efficiency make our method attractive for clinical use. 

PMID- 25860300
TI  - Prebiotic glycosylation of uracil with electron-donating substituents.
AB  - Following the suggestion that nucleoside analogues having their nucleobases
      joined to ribose via a carbon-carbon bond might easily arise prebiotically, the
      glycosylation of uracil carrying electron-donating substituents (Me, OH, OCH3,
      NH2) at its 5 or 6 positions was investigated. Of these, only 6-aminouracil gave
      glycosylated products in greater than 50% yield under simulated prebiotic
      conditions. The reaction provided four products, three of which were purified by
      preparative HPLC. The structure of the isolated compounds was determined by high
      resolution mass spectrometry and NMR spectroscopy. The glycosylation products
      were, as expected, C-nucleosides, with the sugar having either a pyranose or a
      furanose structure, with the ratio depending on the precise conditions, implying
      reversible addition. Interestingly, the 6-aminouracil riboside displays two
      hydrogen bonding patterns, the "acceptor-donor-acceptor" pattern of uridine
      itself and (upon 180 degrees  rotation) the "acceptor-donor-donor" hydrogen
      bonding pattern. The second, in an artificially expanded genetic information
      system, is trivially called "V" and pairs with a purine analogue that presents
      the complementary "donor-acceptor-acceptor" hydrogen bonding pattern, trivially
      called "J."

PMID- 25860301
TI  - Synthesis of beta-Thiol Phenylalanine for Applications in One-Pot Ligation
      Desulfurization Chemistry.
AB  - The efficient synthesis of a beta-thiol phenylalanine derivative is described
      starting from Garner's aldehyde. The utility of this amino acid in peptide
      ligation-desulfurization chemistry is described, including the
      trifluoroethanethiol (TFET)-promoted one-pot assembly of the 62 residue peptide
      hormone augurin. 

PMID- 25860302
TI  - Autism spectrum disorders-Global challenges and local opportunities.

PMID- 25860303
TI  - Towards a theory-based positive youth development programme.
AB  - The aim of this study was to develop and describe an intervention programme for
      young adolescents, guided by the Positive Youth Development Intervention (PYDI)
      model, which provides a perspective on the facilitation of development in a more
      positive trajectory. The key concepts and processes suggested by the PYDI model
      were further analysed and broadened using existing literature for
      operationalisation and application purposes. Self-regulation is the central
      process effectuating developmental change, within the contexts of: a) the
      navigation of stressors; and b) the formulation and effective pursuit of relevant
      personal goals. Self-regulation, together with a developmental perspective,
      provided guidelines regarding the relevant skills and knowledge. These are
      facilitating: a) identity development; b) formulation of goals congruent with the
      latter; c) decision-making skills; d) coping skills; e) regulation of affect and
      cognition; and f) socialisation skills. The relevant content areas and the manner
      of the facilitation of these are indicated. The theory-based programme can be
      implemented and its effect empirically evaluated. Levels of hope, problem-solving
      efficacy and social efficacy may serve as, inter alia, indicators of
      developmental change. 

PMID- 25860304
TI  - Development and preliminary validation of a screen for interpersonal childhood
      trauma experiences among school-going youth in Durban, South Africa.
AB  - This paper describes the development and preliminary validation of the
      Developmental Trauma Inventory (DTI), which is a 36-item, retrospective, self
      administered screen for interpersonal childhood trauma experiences developed
      specifically for the South African context. Preliminary validation of the
      inventory was conducted using a sample of 720 school-going adolescents attending
      a high school in the Durban Metropolitan area (South Africa). Factor analysis
      produced the best fit for a 10-factor model (emotional abuse, community assault,
      domestic assault, poverty, witnessing community violence, witnessing domestic
      violence, indecent assault, domestic neglect, rape, and domestic injury).
      Contrary to expectations, items relating to loss and separation (e.g. death of a
      parent) did not produce a clear factor structure. Identified scales had good
      internal consistency (0.70 to 0.81), low factor inter-correlations, and high
      concurrent criterion-related validity in the sense that all scales were
      significantly correlated with scores on clinical measures of post-traumatic
      stress disorder (PTSD) and/or complex PTSD. These findings provide preliminary
      support for the utility of DTI in the South African context. 

PMID- 25860305
TI  - Peer education training for sexual health and well-being in public high schools
      in South Africa: Is it enough to change peer educators themselves?
AB  - OBJECTIVE: To evaluate the effects of a high school peer educator training
      programme on the sexual behaviour and related psychosocial outcomes of peer
      educators. METHOD: A total of 728 students from 15 randomly selected public high
      schools in the Western Cape, South Africa, with a peer education programme and 15
      matched comparison schools were recruited, comprising 295 students in the
      intervention group and 433 students in the comparison arms of the study
      respectively. Age of sexual debut, use of condom at last sex and psychosocial
      outcomes such as decision making, goal orientation, critical thinking and self
      esteem were measured at baseline and follow-up 18 months later. RESULTS: At
      follow-up, there were no significant differences in the age of sexual debut, use
      of condom at last sex, goal orientation, critical thinking and self-esteem scores
      of the peer educators compared to students in the comparison group. Decision
      making scores were significantly higher in the peer educators, compared to
      students in the comparison group (adjusted difference between means 0.14, 95% CI
      0.02 to 0.26). CONCLUSION: Even a highly intensive peer education training
      programme had limited effects for the peer educators themselves. It is clear that
      community factors, gendered power relations and poverty need to be addressed to
      have a lasting impact.

PMID- 25860306
TI  - Prevalence and factors associated with depressive symptoms among young women and
      men in the Eastern Cape Province, South Africa.
AB  - PURPOSE: There is little research on prevalence of depressive symptoms and
      associated factors among youth in sub-Saharan Africa. This paper explores factors
      associated with depressive symptomatology in South Africa. METHODS: A cross
      sectional analysis of interviews with 1 415 women and 1 368 men aged 15-26 was
      undertaken. The Centre for Epidemiological Studies on Depression Scale (CESD
      Scale) was used to establish depressive symptomatology. RESULTS: The prevalence
      of depressive symptoms was 20.5% in women and 13.5% in men. For women, depressive
      symptoms were associated with increased childhood adversity (aOR 1.34 95% CI
      1.116, 1.55); drug use (aOR 1.98 CI 1.17, 3.35); experience of intimate partner
      violence (aOR 2.21 CI 1.16, 3.00); sexual violence before the age of 18 years
      (aOR 1.45 CI 1.02, 2.02) and lower perceptions of community cohesion (aOR 1.23 CI
      1.07, 1.40). For men, depressive symptoms were associated with a mother's death
      (aOR 2.24 CI 1.25, 4.00); childhood adversity (aOR 1.61 CI 1.38, 1.88); alcohol
      abuse (aOR 1.63 CI 1.13, 2.35), sexual coercion by a woman (aOR 2.36 CI 1.47,
      3.80) and relationship conflict (aOR 1.07 CI 1.01, 1.12). CONCLUSIONS: Depressive
      symptoms were more highly prevalent in women than in men. Depressed mood was
      associated with childhood adversity, sexual violence and substance misuse in both
      women and men. This study further suggests gender differences in that for women,
      depressive symptoms were associated with intimate partner violence and lower
      perceptions of community cohesion, while for men the associations were with a
      mother's death and relationship conflict.

PMID- 25860307
TI  - Cradling bias is absent in children with autism spectrum disorders.
AB  - OBJECTIVE: This study investigated relations among empathy and cradling bias in
      children diagnosed with autism spectrum disorders (ASDs). METHOD: Twenty children
      with ASDs and 20 typically developing (TD) children, aged 5-15 years old, cradled
      a doll as if it were an infant s/he was putting to sleep on three separate
      occasions. We recorded side preference on each occasion. RESULTS: Children with
      ASDs showed no preference for cradling side whereas TD children showed a strong
      left-sided preference. To the best of our knowledge, children with ASDs are the
      only population that does not exhibit cradling bias. CONCLUSION: An absence of
      cradling bias and empathy deficits in ASD may be related. If so, these data
      support the hypothesis that leftward cradling is a characteristic of enhanced
      quality of caregiver-infant interaction and bonding.

PMID- 25860308
TI  - Cannabis use and family history in adolescent first episode psychosis in Durban,
      South Africa.
AB  - OBJECTIVES: To investigate the clinical correlates of cannabis use in adolescents
      with first episode psychosis (FEP). METHODS: Inpatient psychiatric records
      provided demographic, lifetime cannabis use, family history of mental illness,
      and clinical data on 45 FEP adolescents, aged 12-18 years, admitted to a
      psychiatric unit in Durban, KwaZulu-Natal, South Africa, over a 2-year period.
      RESULTS: Thirty-one (68.8%) of the 45 FEP adolescents reported a history of
      lifetime cannabis use. The age of FEP presentation and pre-diagnosis symptom
      duration was not significantly different in cannabis users versus non cannabis
      users. Of the 15/43 (34.8%) FEP patients with family history of mental illness,
      10 had a history of cannabis use. The 26 (57.8%) schizophrenia spectrum disorder
      patients did not differ significantly from the 19 (42.2%) with other psychoses in
      terms of cannabis use and family history of mental illness. They were, however,
      significantly younger at age of presentation and had a significantly longer
      duration of pre-diagnosis symptoms. CONCLUSIONS: These preliminary findings
      suggest a high prevalence of cannabis use in adolescents with FEP and highlight
      the public health concern of addressing substance abuse in the adolescent
      population.

PMID- 25860309
TI  - Prevalence and patterns of medication use in children and adolescents with autism
      spectrum disorders in the Western Cape, South Africa.
AB  - OBJECTIVE: This study was conducted to investigate the prevalence and patterns of
      medication use amongst a sample of school going children and adolescents with
      autism spectrum disorders (ASD) in the Western Cape, South Africa. METHOD: This
      was a descriptive, quantitative, analytic study. A survey questionnaire and the
      Nisonger Child Behaviour Rating Form (NCBRF) were administered to parents of
      children and adolescents recruited from two schools for children with ASD in Cape
      Town and from the Autism Action database. RESULTS: A total of 24.6% of the 65
      children used psychotropic medications. Antipsychotics were the most common
      reportedly used psychotropics followed by stimulants, antidepressants and mood
      stabilisers. Complementary and alternative medications were also commonly used
      with 40% of children using over the counter medications (OTC) and 15.4% being on
      a special diet for autism. Children of black African or coloured ethnicity were
      less likely to use OTC medication than children in the white/ Asian ethnic group.
      CONCLUSIONS: In keeping with international studies this sample of children with
      ASD was a highly medicated group. The findings of this pilot study were limited
      by the response rates and sample size, but provide valuable insight into
      medication use in the South African ASD population.

PMID- 25860310
TI  - Evaluation of a school-based intervention programme for South African children of
      divorce.
AB  - OBJECTIVE: Parental divorce affects approximately 30 000 South African children
      annually. This pilot study aimed to evaluate the effectiveness of the Children of
      Divorce Intervention Programme (CODIP) at two South African schools. CODIP is a
      preventively oriented group programme which was developed to foster resilience by
      helping children cope more effectively with possible academic, behavioural, and
      emotional problems brought about by their parents' divorce. METHOD: Twenty-five
      10- to 14-year-old boys from two primary schools were randomly assigned to 2
      experimental groups and 1 delayed intervention control group. The experimental
      groups attended 12 one-hour weekly sessions; the control group received no
      intervention until after the study was completed. Children's understanding of
      divorce related events and social, emotional and behavioural adjustment was
      assessed one week before the intervention and three months thereafter using a
      battery of self-rated, teacher-rated and parent-rated questionnaires. RESULTS:
      One-way ANOVAs indicated no statistically significant decline in children's self
      reported problematic beliefs about divorce or total difficulties. However,
      teachers' and parents' ratings indicated that compared to the control group, the
      combined experimental groups showed significant improvement in their general
      behavioural, emotional and social adjustment after programme participation.
      CONCLUSIONS: The results suggest that South African children who experience
      parental divorce may benefit from participation in CODIP.

PMID- 25860311
TI  - Social skills for teenagers with developmental and autism spectrum disorders: The
      PEERS treatment manual.

PMID- 25860312
TI  - Treating attachment disorders-From theory to therapy (Second edition).

PMID- 25860313
TI  - Journal abstracts from current research in the field of child and adolescent
      mental health.

PMID- 25860315
TI  - Surface enhanced Raman scattering of amino acids assisted by gold nanoparticles
      and Gd(3+) ions.
AB  - The surface enhanced raman scattering (SERS) signal from the l-tyrosine (tyr)
      molecule adsorbed on gold nanoparticles (Au-tyr) is compared with the SERS signal
      assisted by the presence of gadolinium ions (Gd(3+)) coordinated with the Au-tyr
      system. An enhancement factor of the SERS signal in the presence of Gd(3+) ions
      was ~5 times higher than that produced by l-tyrosine adsorbed on gold
      nanoparticles. The enhancement of the SERS signal can be attributed to a
      corresponding increase in the local electric field due to the presence of Gd(3+)
      ions in the vicinity of a gold dimer configuration. This scenario was confirmed
      by solving numerically Maxwell equations, showing an increase of 1 order of
      magnitude in the local electric scattered field when the Gd(3+) ion is located in
      between a gold dimer compared with naked gold nanoparticles. 

PMID- 25860316
TI  - Neuropathology of HAND With Suppressive Antiretroviral Therapy: Encephalitis and
      Neurodegeneration Reconsidered.
AB  - HIV-1 infiltrates the central nervous system (CNS) during the initial infection
      and thereafter plays a persistent role in producing CNS dysfunction as the
      disease progresses. HIV-associated neurocognitive disorders (HAND) are highly
      prevalent in HIV-infected patient populations, including currently infected
      patients with good access to suppressive antiretroviral therapy (cART). cART
      decreased the severity of CNS dysfunction dramatically and, in doing so, upended
      the neuropathological foundation of HAND pathophysiology. It is clear that the
      working concept of pathophysiology prior to cART, which was driven by
      inflammation, encephalitis, and neurodegeneration, needs to be replaced. The
      NeuroAIDS field is reluctant to take that important step. This review explores
      the fact that the neuropathological concept that drove the field before the era
      of cART no longer seems to fit with what is commonly observed in patients treated
      successfully with cART. The field clings to the pre-cART idea that HAND is
      sequentially driven by virus replication in CNS, brain inflammation
      (encephalitis), and neurodegeneration. Neurovirological, clinicopathological, and
      gene expression correlations in cART-treated patients, however, provide little
      strong support for it. Introducing cART into clinical practice decreased HIVE,
      inflammation, and degeneration but did not cure HAND. Brain gene array data
      suggest that the neurovascular unit is a critical target in virally suppressed
      patients with HAND. The NeuroAIDS field needs an infusion of new ideas to steer
      research toward issues of the highest relevance to virally suppressed patients.
      With no suitable replacement immediately within reach, devaluating formative
      ideas is understandably difficult to accept. The cliniconeuropathological
      correlation in virally suppressed patients needs to be better defined. 

PMID- 25860318
TI  - Myths or theories? Alternative beliefs about HIV and AIDS in South African
      working class communities.
AB  - Despite three decades of public health promotion based on the scientific
      explanation of HIV/AIDS, alternative explanations of the disease continue to
      circulate. While these are seen as counter-productive to health education
      efforts, what is rarely analysed is their plurality and their tenacity. This
      article analyses the 'AIDS myths' collected by African HIV/AIDS workplace peer
      educators during an action research project. These beliefs about HIV/AIDS are
      organised, in this article, around core ideas that form the basis of 'folk' and
      'lay theories' of HIV/AIDS. These constitute non-scientific explanations of
      HIV/AIDS, with folk theories drawing on bodies of knowledge that are independent
      of HIV/AIDS while lay theories are generated in response to the disease. A
      categorisation of alternative beliefs about HIV/AIDS is presented which comprises
      three folk theories - African traditional beliefs, Christian theology, and racial
      conspiracy - and three lay theories, all focused on avoiding HIV infection. Using
      this schema, the article describes how the plausibility of these alternative
      theories of HIV/AIDS lies not in their scientific validity, but in the robustness
      of the core idea at the heart of each folk or lay theory. Folk and lay theories
      of HIV/AIDS are also often highly palatable in that they provide hope and comfort
      in terms of prevention, cure, and the allocation of blame. This study argue that
      there is coherence and value to these alternative HIV/AIDS beliefs which should
      not be dismissed as ignorance, idle speculation or simple misunderstandings. A
      serious engagement with folk and lay theories of HIV/AIDS helps explain the
      continued circulation of alternative beliefs of HIV/AIDS and the slow uptake of
      behavioural change messages around the disease. 

PMID- 25860317
TI  - Cerebrospinal Fluid HIV Escape from Antiretroviral Therapy.
AB  - CNS infection is a nearly constant facet of systemic CNS infection and is
      generally well controlled by suppressive systemic antiretroviral therapy (ART).
      However, there are instances when HIV can be detected in the cerebrospinal fluid
      (CSF) despite suppression of plasma viruses below the clinical limits of
      measurement. We review three types of CSF viral escape: asymptomatic, neuro
      symptomatic, and secondary. The first, asymptomatic CSF escape, is seemingly
      benign and characterized by lack of discernable neurological deterioration or
      subsequent CNS disease progression. Neuro-symptomatic CSF escape is an uncommon,
      but important, entity characterized by new or progressive CNS disease that is
      critical to recognize clinically because of its management implications. Finally,
      secondary CSF escape, which may be even more uncommon, is defined by an increase
      of CSF HIV replication in association with a concomitant non-HIV infection, as a
      consequence of the local inflammatory response. Understanding these CSF escape
      settings not only is important for clinical diagnosis and management but also may
      provide insight into the CNS HIV reservoir. 

PMID- 25860319
TI  - The impact of church contextual factors on church-going youth's HIV prevention
      behaviour in Nairobi, Kenya: A cross-denominational study.
AB  - Church doctrine about sexual behaviour has long been assumed to have an impact on
      aspects of the sub-Saharan AIDS epidemic, and evidence suggests that Pentecostal
      churches have a stronger influence THAN? on the sexual behaviour of their
      adherents. However, few studies have investigated the denominational differences
      in sexual attitudes and behaviour of youths, and virtually no empirical evidence
      is available regarding what specific aspects of the church environment are
      associated with differences in the response of youths to church messaging about
      sexual behaviour. This study examined those factors among church-going youth in
      Nairobi, Kenya. Separate focus groups with male and female youths were conducted
      in four mainline and three Pentecostal/evangelical (P/E) churches, and in-depth
      interviews were conducted with youth pastors or pastors of five of those
      churches. Content of church teaching as reported by youths and pastors did not
      differ between denominations. However, amount and context of teaching did vary,
      with P/E churches reportedly offering more teaching about sex to their youth. In
      addition, P/E churches appeared to provide a more intense experience of community
      than mainline churches, a situation that may create a context within which
      abstinence appears to be a reasonable life choice. 

PMID- 25860320
TI  - Acceptability of routine HIV counselling and testing among a sample of South
      African students: Testing the Health Belief Model.
AB  - Routine HIV counseling and testing (RCT) is a necessary first step in accessing
      health care for persons who may test HIV-positive. Despite the availability of
      RCT in many South African settings, uptake has often been low. We sought to
      determine whether the main components of the Health Belief Model (HBM), namely
      perceived susceptibility, perceived severity, perceived benefits and perceived
      barriers could predict acceptance of RCT, and whether cues to action predicted
      uptake of RCT. A sample of 1 113 students at a large South African university
      completed a battery of instruments measuring acceptability of RCT, previous
      uptake of HIV testing, and the various HBM variables. Regression analysis showed
      that perceived susceptibility to HIV, perceived severity of HIV, perceived
      benefits of RCT, and perceived barriers to RCT explained 25.1% of the variance in
      acceptance of RCT. The findings of the study are located in the context of
      existing literature on RCT. 

PMID- 25860321
TI  - Cost-effectiveness analysis of infant feeding strategies to prevent mother-to
      child transmission of HIV in South Africa.
AB  - Despite increasing availability of perinatal interventions to prevent mother-to
      child transmission (MTCT) of HIV in South Africa, MTCT remains high due to
      breastfeeding. To inform policy decisions in the country, cost-effectiveness of
      alternative infant-feeding interventions was conducted. Mathematical modelling
      was used to simulate post-natal transmission and mortality due to infant feeding
      in a hypothetical cohort of 1 000 HIV-exposed infants. Lifetime costs to the
      health system were calculated for each strategy. Interventions compared with
      current practice were: increasing coverage of extended nevirapine prophylaxis
      (ENP) to infants from 30% (base case) to 60% without changing current feeding
      practices; actively supporting breastfeeding with ENP to infants for 12 months;
      and actively supporting exclusive formula (replacement) feeding for 6 months. HIV
      free survival at 24 months and disability-adjusted life years (DALYs) averted
      were estimated for typical rural and certain urban settings. Base-case analysis
      revealed that expanding coverage of nevirapine prophylaxis with breastfeeding is
      cost-saving and improves HIV-free survival. Changing feeding practices is
      beneficial, depending on context. Breastfeeding is dominant (less costly, more
      effective) in rural settings, whilst formula feeding is a dominant strategy in
      urban settings. Cost-effectiveness was most sensitive to proportion of women on
      lifelong antiretroviral therapy (ART) and infant mortality rate (IMR). When >55%
      of women are on ART, breastfeeding dominates in the urban settings modelled,
      whilst formula feeding is cost-effective in rural settings when IMR <= 45/1000.
      The study concludes that strategies to support breastfeeding are essential.
      Strengthening health systems is critical to ensure optimal nevirapine delivery
      during breastfeeding. A case can be made for formula feeding or breastfeeding in
      HIV-infected women in specific contexts. 

PMID- 25860322
TI  - Have the educated changed HIV risk behaviours more in Africa?
AB  - Theory predicts that when new health information becomes available, more educated
      individuals may adopt healthy behaviours sooner, resulting in lower morbidity and
      mortality among the highly educated. This may be the case for HIV in sub-Saharan
      Africa: Recent empirical work shows that incidence is falling and the reduction
      is concentrated in more educated populations. However, it is unclear whether the
      educated have indeed adopted HIV risk-reducing behaviours to a greater extent
      than the less educated. I used two rounds of demographic and health surveys (DHS)
      in eight African countries to examine whether HIV-related behavioural change over
      time is greater among the more highly educated. I examined changes in condom use,
      age of marriage, number of partners, extramarital partnerships, and HIV testing.
      Results showed that education has a robust positive association with condom use
      and HIV testing, but also with having more sexual partners. I found that the
      probability of HIV testing increased more between rounds among the more educated,
      relative to the less educated. More educated men also appeared to have larger
      reductions in the number of sexual partners and there was evidence that younger,
      more educated women may be marrying earlier than their predecessors did. The
      education gradient did not change significantly over time for condom use. These
      changes in behaviour may signal a shift in the future burden of the epidemic
      towards more marginalised and less educated populations. 

PMID- 25860323
TI  - Management of the first stage of labor: potential strategies to lower the
      cesarean delivery rate.
AB  - To review management strategies associated with lower risk for cesarean delivery.
      Targeted literature review for labor interventions during the first stage of
      labor. There is evidence that policies regarding labor admission criteria,
      standardized policies regarding labor management including judicious use of
      oxytocin, standardized terminology and treatment for electronic fetal monitoring,
      standardized criteria for dystocia, and systematic implementation of policies
      that incorporate continuous supportive care during labor are associated with
      lower risk for cesarean. Evidence regarding use of amniotomy is conflicting.
      Management of the first stage of labor can affect the risk for cesarean delivery.

PMID- 25860324
TI  - State of family planning.
AB  - Family planning and reproductive health services are uniquely impacted by policy
      and politics in the United States. Recent years have witnessed an unprecedented
      number of abortion restrictions, and research funding has decreased in related
      areas. Despite this, both the science and the implementation of improved family
      planning and abortion methods have progressed in the past decade. This article
      reviews the current state of family planning, as well as technologies and patient
      care opportunities for the future. 

PMID- 25860325
TI  - Cesarean delivery as a marker for obstetric quality.
AB  - Cesarean delivery is a frequent, easily obtainable, and meaningful event in
      obstetrics that has frequently been used as a quality indicator. However, its
      utility as a widespread marker of quality has several limitations. The cesarean
      delivery rate does not account for variation in levels of maternal care with
      varying maternal and fetal conditions. Attempts to risk adjust with the
      nulliparous, singleton, term, vertex cesarean, or the vaginal birth after
      cesarean rates fall short as, in obstetrics, it is the outcome of 2 patients, the
      mother and the infant, that ultimately matters. Newer and more sophisticated
      measures are increasingly available and offer greater potential to improve care
      for mothers and babies. However, much work is needed to create better quality
      metrics for obstetric care that can be measured and validated to truly reflect
      the quality of care women are receiving. 

PMID- 25860326
TI  - Improving Medicaid: three decades of change to better serve women of childbearing
      age.
AB  - Over the past 3 decades, major changes enhanced Medicaid's role in improving the
      health of women and perinatal outcomes. Reforms in the 1980s and 1990s had impact
      not only on coverage but also on current policy debates. Whether or not states
      expand eligibility under the Affordable Care Act, Medicaid is important.
      Increased coverage for well-woman visits, preconception care, and contraceptive
      methods are opportunities in gynecology. As a critical source of maternity
      coverage, Medicaid can improve prenatal care, reduce preterm births, limit early
      elective deliveries, and increase postpartum visits. Obstetrician-gynecologists
      play a role in translating coverage into access to quality services. 

PMID- 25860328
TI  - The cost of ipilimumab toxicity: a single-centre analysis.
AB  - There are no published data on the costs associated with investigating and
      managing toxicity from ipilimumab treatment in patients with metastatic melanoma.
      Patients treated with ipilimumab at The Royal Marsden Hospital between 1
      September 2010 and 1 April 2013 were identified. Data on demographics,
      investigations and survival outcomes were collected. Patients with grade 3 or
      higher immune-related adverse events were identified, and costs of investigating
      and managing toxicities in them were calculated on the basis of standard National
      Health Service tariffs. Out of the 110 patients, 29 experienced grade 3/4 immune
      related adverse events. The total cost of investigating and managing these
      patients was L140,680, or a median cost of L2860 per patient. Patients
      experiencing grade 3/4 toxicities had 1-, 2- and 3-year survival rates of 79, 59
      and 46%, compared with 24, 17 and 15% in the group that did not experience
      significant toxicity (P<0.0005). The most common treatment-related toxicity
      identified was colitis. Two patients died from complications associated with
      ipilimumab colitis. The cost of ipilimumab toxicity is marginal in comparison
      with the total treatment cost. Patients treated with ipilimumab who develop
      significant toxicity have a higher than expected 1-, 2- and 3-year survival.

PMID- 25860329
TI  - Clinical outcomes associated with serial sharp debridement of diabetic foot
      ulcers with and without clostridial collagenase ointment.
AB  - OBJECTIVE: Fifty-five subjects with diabetes mellitus type 1 or 2 and a
      neuropathic, nonischemic foot ulcer were enrolled into this randomized,
      controlled, multicenter trial designed to examine the effects of debridement with
      clostridial collagenase ointment (CCO) used in conjunction with serial sharp
      debridement for a period of 6 weeks. METHODS: Serial sharp debridement without
      adjunctive CCO was used in the control group. Various standard care therapies
      thought to support debridement by endogenous proteases were selected at the
      discretion of the investigators for use in the control group. The primary outcome
      measure of this trial was the percent change in ulcer area from baseline at the
      end of the debridement/treatment period (EOT) and at the end of an additional 6
      weeks of follow-up (EOS). Secondary objectives were to assess wound status at EOT
      and EOS using a standardized wound assessment tool, and to compare the average
      time to closure for ulcers debrided with serial sharp debridement with and
      without adjunctive CCO. RESULTS: Wound area decreased relative to baseline for
      both the CCO group (-68%, -61%) and the control group (-36%, -46%) at EOT and
      EOS, respectively. While the inter-group differences did not reach statistical
      significance, wound area was significantly decreased from baseline at both EOT
      and EOS for the CCO (P < 0.001) but not for the control group. Wound status
      scores (scale range 8 to 40) improved for both groups during treatment (CCO: 
      3.5, control: -3.2) and follow-up (CCO: -5.3, control: -6.4). No differences were
      observed in the number of sharp debridements (CCO: 3.7, control: 4.0). Median
      time to closure for wounds that healed was 6 weeks for CCO and 8 weeks for
      control. On average, ulcers treated with serial sharp debridement plus adjunctive
      CCO decreased in size more rapidly than ulcers treated without adjunctive CCO
      debridement. No safety issues were identified based on a review of reported
      adverse events. CONCLUSION: These results suggest there is more to wound
      debridement than meets the eye, and establish a foundation for larger,
      confirmatory studies.

PMID- 25860330
TI  - Treating peripheral neuropathy.
AB  - Peripheral neuropathy (PN) is a serious problem affecting more than 22 million
      people in the United States, according to The Pacific Chapter of the Neuropathy
      Association. One in 5 Americans will be diagnosed with this condition during
      their lifetime, including up to 60% of people with diabetes. Currently there is
      no cure for neuropathy. Treatment options are quite minimal, geared towards
      relieving symptoms with medications, but often no treatment of any kind is
      offered to patients. This study is a retrospective review of 48 charts of
      patients treated for PN from January 2008 through June 2010 at the Integrative
      Center for Healing in Cincinnati, Ohio. Treatment of neuropathy used high volt
      pulsed current (HVPC) electrical stimulation (MicroVas, MTI, Tulsa, OK), with a
      secondary therapy of stopping statin medication. Symptoms evaluated were pain,
      numbness, and condition of a wound, if present. With an average of 23 treatments,
      a statistically significant 83% of patients had improvement in at least 1
      symptom. This warrants further study in treatment of neuropathy with HVPC
      electrical stimulation and/or stopping statin therapy.    . 

PMID- 25860331
TI  - Acroangiodermatitis (Pseudo-Kaposi's Sarcoma) Seen in Conjunction with Marfan
      Syndrome and a Hypercoagulable State: Is There a Link?
AB  - A case study of acroangiodermatitis is presented in conjunction with chronic
      venous disease, Marfan syndrome, and a hypercoagulable state. A possible link
      between acroangiodermatitis and Marfan syndrome is explored. 

PMID- 25860332
TI  - The impact of stress at dressing change in patients with burns: a review of the
      literature on pain and itching.
AB  - Burn wounds can be particularly painful and stressful for patients, particularly
      during dressing change and other aspects of wound care. Research into other types
      of wounds has demonstrated that stress and pain at dressing change are closely
      linked and related to healing, since high levels of stress and pain are
      associated with a longer length of time for a wound to heal. Additionally, there
      is some evidence to suggest a similar relationship between stress and itching.
      This article presents a review of the literature into stress, pain, and itching
      in patients with burns. The review demonstrates the importance of dressing change
      management with these patients. Furthermore, suggestions are made for areas of
      research that are yet to be explored, as such research, and the findings that
      emerge, could have important implications for clinical practice when working with
      people with burns. The common focus of such studies should be the aim of
      minimizing stress and discomfort for people with burns and other wounds so as to
      improve patient well being and treatment outcomes. 

PMID- 25860333
TI  - Therapeutic effects of oleuropein on wounded skin in young male BALB/c mice.
AB  - INTRODUCTION: Oleuropein is generally the most abundant phenolic compound in
      olive leaves. In this study, therapeutic effects of oleuropein were studied on
      wounded skin in young male Balb/c mice. METHODS: Four-month-old male Balb/c mice
      were randomized into 2 groups, a control and an experimental group. Under ether
      anesthesia, hair on the neck of mice in both groups was shaved and 1-cm long full
      thickness incisions were made and left unsutured. The experimental group was
      injected intradermally with a daily single dose of oleuropein (50 mg/kg) for a
      total of 7 days. The control group received only distilled water. On days 3 and 7
      post-incision, mice were sacrificed and skin around the area of the incisions
      were dissected and processed for hematoxylin and eosin and Van Gieson's staining.
      Portions of dissected tissues were also lysed and used for western blot analysis
      to evaluate the level of vascular endothelial growth factor (VEGF) protein
      expression. RESULTS: The analyses showed oleuropein reduced cell infiltration
      into the wound sites on day 3 and 7 postincision; however, it significantly
      increased collagen fiber deposition and caused faster reepithelialization when
      compared to the control group (P < 0.05). Furthermore, western blot analysis
      showed a significant increase in VEGF protein level compared to the control group
      (P < 0.05). CONCLUSION: In summary, oleuropein showed healing effects on wounded
      skin by accelerating the reepithelialization process, enhancing collagen fiber
      generation, and increasing the blood supply to the wounded area by upregulation
      of VEGF protein expression.

PMID- 25860334
TI  - Effects of age and season on haematological parameters of donkeys during the
      rainy and cold-dry seasons.
AB  - The aim of the study was to investigate the effects of age and season on
      haematological parameters of donkeys at rest during the rainy and cold-dry
      seasons. Thirty healthy donkeys divided into three groups based on their age
      served as the subjects. During each season, blood sample was collected from each
      donkey thrice, 2 weeks apart, for haematological analysis, and the dry-bulb
      temperature (DBT), relative humidity (RH) and temperature-humidity index (THI)
      were obtained thrice each day during the experimental period using standard
      procedures. During the rainy season, the mean DBT (33.05 +/- 0.49  degrees C), RH
      (73.63 +/- 1.09 %) and THI (84.39 +/- 0.71) were higher (P < 0.0001) than the
      corresponding values of 24.00 +/- 0.44  degrees C, 36.80 +/- 0.92 % and 64.80 +/-
      0.62, during the cold-dry season. Packed cell volume (PCV), erythrocyte count
      [red blood cell (RBC)], haemoglobin concentration (Hb), mean corpuscular volume
      (MCV), mean corpuscular haemoglobin (MCH), platelet count (PLT), leucocyte count
      [white blood cell (WBC)], lymphocyte count (LYM) and neutrophil/lymphocyte ratio
      (N/L) were higher (P < 0.05) in adults than foals during the rainy season. The
      MCV, MCH, WBC, NEU, LYM and PLT of adult and yearling donkeys were higher (P <
      0.05) during the rainy than the cold-dry season. The PCV, RBC, Hb, MCV, MCH, and
      NEU of foals were higher in the rainy than the cold-dry season. The N/L of adult
      and foal donkeys were higher (P < 0.05) in the rainy than in the cold-dry season.
      In conclusion, PCV, RBC, Hb and LYM were considerably higher in foals than
      yearlings or adults during the rainy season, while erythrocytic indices and
      platelet counts were higher in adults or yearlings than in foals in both seasons.
      Erythrocytic indices, PLT and N/L were higher in the rainy than the cold-dry
      season in adults, yearlings and foals.

PMID- 25860335
TI  - Isomorphism and similarity for 2-generation pedigrees.
AB  - We consider the emerging problem of comparing the similarity between (unlabeled)
      pedigrees. More specifically, we focus on the simplest pedigrees, namely, the 2
      generation pedigrees. We show that the isomorphism testing for two 2-generation
      pedigrees is GI-hard. If the 2-generation pedigrees are monogamous (i.e., each
      individual at level-1 can mate with exactly one partner) then the isomorphism
      testing problem can be solved in polynomial time. We then consider the problem by
      relaxing it into an NP-complete decomposition problem which can be formulated as
      the Minimum Common Integer Pair Partition (MCIPP) problem, which we show to be
      FPT by exploiting a property of the optimal solution. While there is still some
      difficulty to overcome, this lays down a solid foundation for this research. 

PMID- 25860336
TI  - Potential risk of isoflavones: toxicological study of daidzein supplementation in
      piglets.
AB  - As a main component of soy isoflavones, daidzein is rich in soy-derived products,
      which are widely used as feed ingredients in farm animals. However, little
      research has been conducted on the side effects of dietary daidzein, especially
      in young animals. In this study, the safety of daidzein was evaluated. Results
      show that ingesting 400 mg/kg of dietary daidzein for 70 days is associated with
      a lower average daily weight gain (kilogram) (0.47 +/- 0.03 vs 0.54 +/- 0.04, P <
      0.05) and a higher splenic damage index (1.00 +/- 1.10 vs 0.00 +/- 0.00, P <
      0.05) in young pigs compared with control. Female pigs receiving 200 and 400
      mg/kg daidzein showed reduced serum testosterone levels (ng/L) on days 35 and 70
      compared with the control group (day 35, 246 +/- 74 and 224 +/- 20 vs 362 +/- 48,
      P < 0.05; day 70, 252 +/- 38 and 219 +/- 77 vs 374 +/- 38, P < 0.05). Daidzein
      residue (MUg/kg) in pig livers increased (243 +/- 80 vs 142 +/- 47, P < 0.05, day
      70). These results suggest that dietary supplements of 400 mg/kg of daidzein
      negatively affect the weight gain and splenic morphology of pigs. 

PMID- 25860337
TI  - Identification of the hot-spot areas for sickle cell disease using cord blood
      screening at a district hospital: an Indian perspective.
AB  - Sickle cell disease (SCD), a genetic disorder often reported late, can be
      identified early in life, and hot-spot areas may be identified to conduct genetic
      epidemiology studies. This study was undertaken to estimate prevalence and to
      identify hot spot area for SCD in Kalahandi district, by screening cord blood of
      neonates delivered at the district hospital as first-hand information. Kalahandi
      District Hospital selected for the study is predominated by tribal population
      with higher prevalence of SCD as compared to other parts of Odisha. Cord blood
      screening of SCD was carried out on 761 newborn samples of which 13 were screened
      to be homozygous for SCD. Information on area of parent's residence was also
      collected. Madanpur Rampur area was found to be with the highest prevalence of
      SCD (10.52 %) and the gene distribution did not follow Hardy-Weinberg Equation
      indicating un-natural selection. The approach of conducting neonatal screening in
      a district hospital for identification of SCD is feasible and appropriate for
      prioritizing area for the implementation of large-scale screening and planning
      control measures thereof. 

PMID- 25860338
TI  - Association between intraoperative blood pressure and postoperative delirium in
      elderly hip fracture patients.
AB  - BACKGROUND: One possible area of intervention to prevent postoperative delirium
      (PD) is intraoperative blood pressure management. However, the relationship
      between intraoperative blood pressure and PD is unclear. A secondary analysis of
      a RCT study examining the PD risk over the range of absolute intraoperative mean
      arterial blood pressure (MAP) readings and the corresponding relative changes
      from preoperative baseline level was performed to determine the role of MAP on
      PD. METHODS: Nonparametric locally weighted quadratic polynomial smoothing
      (LOESS) regression explored the pattern of PD risk at postoperative day 2 as a
      function of mean surgery MAP (msMAP) and percent change of msMAP from baseline in
      103 elderly hip fracture patients. Segment-linear logistic regression models were
      then constructed to determine the odds ratios (OR) of PD over the observed range
      of these msMAP measures, adjusting for potential confounds. RESULTS: Twenty-three
      patients (22%) developed PD on day 2. LOESS regression revealed a j-shaped
      association between absolute levels of msMAP and PD risk. When msMAP was >=80
      mmHg, higher msMAP imparted greater PD risk (OR = 2.28 per 10 mmHg msMAP
      increase; 95% CI: 1.11-4.70), while higher msMAP was associated with lower PD
      risk (OR = 0.19 per 10 mmHg increase; CI: 0.05-0.76) if msMAP was <80 mmHg. There
      was no statistically significant relationship between PD risk and average percent
      change from baseline in these msMAP measures. CONCLUSION: In elderly hip fracture
      patients, both very high and very low levels of msMAP were associated with
      significantly increased risk of PD.

PMID- 25860339
TI  - The GTPase-activating protein Rga1 interacts with Rho3 GTPase and may regulate
      its function in polarized growth in budding yeast.
AB  - In budding yeast, Rga1 negatively regulates the Rho GTPase Cdc42 by acting as a
      GTPase-activating protein (GAP) for Cdc42. To gain insight into the function and
      regulation of Rga1, we overexpressed Rga1 and an N-terminally truncated Rga1-C538
      (a.a. 538-1007) segment. Overexpression of Rga1-C538 but not full-length Rga1
      severely impaired growth and cell morphology in wild-type cells. We show that
      Rga1 is phosphorylated during the cell cycle. The lack of phenotype for full
      length Rga1 upon overexpression may result from a negative regulation by G1
      specific Pho85, a cyclin-dependent kinase (CDK). From a high-copy suppressor
      screen, we isolated RHO3, SEC9, SEC1, SSO1, SSO2, and SRO7, genes involved in
      exocytosis, as suppressors of the growth defect caused by Rga1-C538
      overexpression. Moreover, we detected that Rga1 interacts with Rho3 in two-hybrid
      and bimolecular fluorescence complementation (BiFC) assays. Rga1 preferentially
      interacts with the GTP-bound form of Rho3 and the interaction requires the GAP
      domain and additional sequence upstream of the GAP domain. Our data suggest that
      the interaction of Rga1 with Rho3 may regulate Rho3's function in polarized bud
      growth. 

PMID- 25860340
TI  - Clathrin Heavy Chain Interacts With Estrogen Receptor alpha and Modulates 17beta
      Estradiol Signaling.
AB  - 17beta-estradiol (E2)-induced signaling and control of estrogen receptor
      (ER)alpha degradation both play a major role in breast cancer cell proliferation.
      We recently reported the involvement of lysosomal function in both E2-dependent
      ERalpha breakdown and E2-induced cell proliferation and thus hypothesized a role
      for endocytic proteins in ERalpha signaling. An small interfering RNA screen
      identified proteins that regulate intracellular endocytic traffic and whose
      silencing alters E2-induced ERalpha degradation. One such protein was the
      clathrin heavy chain (CHC), whose role in E2:ERalpha signaling to cell
      proliferation is unknown. Here, we show that CHC physically interacts with
      ERalpha in the cytoplasm of breast cancer cells and regulates E2-induced cell
      proliferation. Surprisingly, the CHC:ERalpha interaction is required to sustain
      E2 signaling but is dispensable for ERalpha degradation. Our data also
      demonstrate that many membrane trafficking proteins contribute to the regulation
      of ERalpha degradation, thus unraveling the contribution of endocytic proteins in
      E2:ERalpha signaling. 

PMID- 25860341
TI  - Different modes of lipid binding to membrane proteins probed by mass
      spectrometry.
AB  - The realization that the lipid environment is crucial for maintaining the
      structure and function of membrane proteins prompts new methods to understand
      lipid interactions. One such method, mass spectrometry, is emerging with the
      potential to monitor different modes of lipid binding to membrane protein
      complexes. Initial studies monitored the addition of lipids and deduced the
      kinetic and thermodynamic effects of lipid binding to proteins. Recent efforts
      however have focused on identifying lipids already present, explicitly in plugs,
      annular rings, or cavities. Lipids that bind within these orifices to membrane
      proteins will have higher residence times than those in the bulk lipid bilayer
      and consequently can be quantified and characterized by mass spectrometry. In
      special cases, lipids identified within cavities have been proposed as substrates
      following activity assays. Alternatively, a gas-phase unfolding protocol can be
      used to distinguish lipids that are important for stability. These lipids can
      subsequently be added during crystallization for the characterization of lipid
      bound protein complexes. Overall therefore this Perspective provides an overview
      of recent advances in mass spectrometry, with a particular focus on the
      distinction of the various modes of lipid binding, and their implications for
      structure and function as well as new directions that lie ahead. 

PMID- 25860342
TI  - Diffusion-weighted MRI findings and clinical correlations in sporadic Creutzfeldt
      Jakob disease.
AB  - The objective of this study is to investigate the hyperintense lesions on
      diffusion-weighted magnetic resonance imaging (DWI) and its clinical correlation
      in sporadic Creutzfeldt-Jakob disease (sCJD). Patients who suffered from sCJD and
      followed up at the Department of Neurology at the General Hospital of the
      People's Liberation Army during the period of June 1, 2007 to July 1, 2014 were
      reviewed. The location of the hyperintense lesions on DWI, apparent diffusion
      coefficient (ADC) values of the hyperintense lesions were correlated with
      symptoms and clinical course. A total of 58 sCJD patients and ten healthy
      controls were included. Hyperintense lesions on DWI were observed in all the
      patients. The patients with basal ganglia (BG) hyperintense lesions on DWI had
      shorter disease duration and higher incidence of myoclonus (92 versus 44 %) than
      those without BG hyperintense lesions. The patients with occipital cortex
      hyperintense lesions on DWI had shorter disease duration between symptom onset
      and akinetic mutism than those without these lesions. The lower of the BG ADC
      value the faster presence of akinetic mutism and the shorter disease duration the
      patients will have. The presence of BG and occipital cortex hyperintense lesions
      on DWI and BG ADC values is correlated with the clinical course and clinical
      symptoms.

PMID- 25860343
TI  - Paranoid delusion as lead symptom in two siblings with late-onset Tay-Sachs
      disease and a novel mutation in the HEXA gene.

PMID- 25860344
TI  - Predicting prognosis in amyotrophic lateral sclerosis: a simple algorithm.
AB  - The objective of the study was to develop and validate a practical prognostic
      index for patients with amyotrophic lateral scleroses (ALS) using information
      available at the first clinical consultation. We interrogated datasets generated
      from two population-based projects (based in the Republic of Ireland and Italy).
      The Irish patient cohort was divided into Training and Test sub-cohorts. Kaplan
      Meier methods and Cox proportional hazards regression were used to identify
      significant predictors of prognoses in the Training set. Using a weighted grading
      system, a prognostic index was derived that separated three risk groups. The
      validity of index was tested in the Irish Test sub-cohort and externally
      confirmed in the Italian replication cohort. In the Training sub-cohort (n =
      117), significant predictors of prognoses were site of disease onset (HR = 1.7, p
      = 0.012); ALSFRS-R slope prior to first evaluation (HR = 2.8, p < 0.0001), and
      executive dysfunction (HR = 2.11, p = 0.001). The risk group system generated
      using these results predicted median survival time in the Training set, the Test
      set (n = 87) and the Italian cohort (n = 122) with no overlap of the 95 % CI (p <
      0.0001). In the validation cohorts, a high-risk classification was associated
      with a positive predictive value for poor prognosis of 73.3-85.7 % and a negative
      predictive value (NPV) for good prognosis of 93.3-100 %. Classification into the
      low-risk group was associated with an NPV for bad prognosis of 100 %. A simple
      algorithm using variables that can be gathered at first patient encounter,
      validated in an independent patient series, reliably predicts prognoses in ALS
      patients.

PMID- 25860345
TI  - Clinical spectrum, underlying etiologies and radiological characteristics of
      cortical superficial siderosis.
AB  - Cortical superficial siderosis (cSS) is an increasingly recognized MR-imaging
      marker most probably caused by focal convexity subarachnoid hemorrhage (SAH).
      There is accumulating evidence that cSS represents an important risk factor for
      subsequent intracranial hemorrhages. Here, we aimed to determine clinical
      symptoms, underlying etiologies, and radiological characteristics of cSS in a
      large patient cohort. We performed an electronic database search on all patients
      who presented between 2002 and 2013 to the university hospital Munich with non
      traumatic and non-aneurysmal cSS. T2*-weighted gradient-echo sequences were
      analyzed regarding localization and extent of cSS as well as of acute SAH,
      intracerebral hemorrhages (ICH) and microbleeds. Besides, all available clinical,
      laboratory, imaging and histological data were analyzed. 113 subjects matched the
      inclusion criteria. The following etiologies for cSS were identified: definite (n
      = 6; 5 %), probable (n = 75; 66 %), and possible (n = 28; 25 %) cerebral amyloid
      angiopathy (CAA); reversible cerebral vasoconstriction syndrome: 2 (2 %); central
      nervous system vasculitis: 1; and hyperperfusion syndrome: 1. Acute ICH was
      evident in 55 (49 %) cases. Other clinical manifestations were: transient focal
      neurological episodes (TFNE): 38 (34 %); cognitive impairment: 14 (12 %);
      generalized seizure: 4 (4 %); and headache: 2 (2 %). Adjusting for age and
      gender, cognitive impairment was more frequent in disseminated cSS, while TFNE
      was more often found in focal cSS (p = 0.042). Our data indicate CAA to be the
      most common etiology of cSS. In absence of symptomatic ICH, patients with focal
      cSS frequently present with TFNE, while those with disseminated cSS commonly
      manifest with cognitive impairment.

PMID- 25860346
TI  - Amyloid and FDG-PET study of logopenic primary progressive aphasia: evidence for
      the existence of two subtypes.
AB  - The logopenic variant of primary progressive aphasia (lvPPA) has been associated
      with Alzheimer disease, although this relationship is still subject to debate.
      The purpose of this study is to determine the frequency of amyloid biomarkers in
      patients with lvPPA, and record any potential clinical or topographic differences
      between patients with and without amyloid deposits. We conducted cognitive
      examination and positron-emission tomography studies with fluorodeoxyglucose
      ((18)F) and florbetapir ((18)F) in a cohort of 16 patients diagnosed with lvPPA.
      We evaluated the prevalence of amyloid deposits as well as any clinical and
      metabolic differences between the groups with and without significant presence of
      amyloid deposits. Eleven patients (69 %) were considered amyloid-positive. The
      amyloid-positive group displayed less metabolic activity in the left
      temporoparietal region than the control group, while the amyloid-negative group
      showed lower metabolism in the left temporoparietal region extending to the
      anterior temporal and basal frontal regions. The percentage of change in patients
      with clinical and FDG-PET follow-up did not differ between the amyloid-positive
      and amyloid-negative subgroups. The frequency of amyloid-positive cases confirms
      that lvPPA is frequently associated with Alzheimer disease. Amyloid-negative
      patients show a different cerebral metabolic pattern. These findings show the
      relevance of using amyloid PET to study lvPPA, and also suggest that the
      logopenic variant may not be specific to Alzheimer disease in certain cases.

PMID- 25860347
TI  - A phase I/II trial of second-line chemotherapy with paclitaxel and irinotecan in
      fluoropyrimidine- and platinum-pretreated patients with advanced gastric cancer.
AB  - BACKGROUND: This is a phase I/II study of second-line chemotherapy with
      paclitaxel and irinotecan in fluoropyrimidine- and platinum-pretreated patients
      with metastatic or recurrent gastric cancer. METHODS: Phase I part with a
      standard 3 + 3 dose-escalation design was conducted to define the recommended
      phase II dose (RP2D) using four predefined dose levels of paclitaxel and
      irinotecan. The efficacy of RP2D was evaluated in a phase II part. RESULTS: In
      phase I part, 12 patients were enrolled. Dose-limiting toxicity was not observed.
      The RP2D was established as level 4 (paclitaxel-135 mg/m(2) and irinotecan-160
      mg/m(2), every 3 weeks). In phase II part, 27 patients were enrolled. Thirty
      patients, including three patients at dose level 4 in the phase I part, were
      analyzed for efficacy. There was no complete response. Partial response and
      stable disease were reported in four and 16 patients, respectively (response rate
      13.3 %, 95 % CI 0.0-25.5 %; disease control rate 66.6 %, 95 % CI 49.0-83.0 %).
      The median time to progression and overall survival was 3.0 months (95 % CI 1.8
      4.2) and 10.1 months (95 % CI 6.6-13.6), respectively. Grade 3/4 toxicities
      included neutropenia (2 patients, 7.4 %), thrombocytopenia (1, 3.7 %),
      neutropenic fever (1, 3.7 %), and diarrhea (1, 3.7 %). There were no treatment
      related deaths. CONCLUSION: The RP2D of the paclitaxel and irinotecan combination
      is paclitaxel (135 mg/m(2)) and irinotecan (160 mg/m(2)), every 3 weeks. This
      combination as a second-line treatment for advanced gastric cancer shows
      tolerable toxicity and modest efficacy.

PMID- 25860349
TI  - Numerical Study on Droplet Sliding across Micropillars.
AB  - Droplet sliding on surfaces is an important phenomenon since it widely happens in
      microfluidic industry. In this article, we simulate droplets sliding across
      micropillars on smooth substrates to test how the pillars with different
      intrinsic wettability influence the movement of droplets. The simulation is
      performed using a particle-based numerical method, many-body dissipative particle
      dynamics (MDPD). The simulated results show that the heterogeneous area (built by
      arranged micropillars) can influence the dynamical contact angles significantly.
      Both the advancing and receding contact angles increase when the droplet front
      slides on the heterogeneous area, and their difference is also enlarged, thus the
      contact line may be pinned. The droplet shows a creeping motion style when its
      front climbs over each pillar. We also find when the droplet enwraps all pillars,
      the composite liquid/solid surfaces have no effect on the advancing and receding
      contact angles. The outcomes support the viewpoint that the wettability is a
      contact-line-based problem instead of a contact-area-based one. 

PMID- 25860348
TI  - 3D structure prediction of human beta1-adrenergic receptor via threading-based
      homology modeling for implications in structure-based drug designing.
AB  - Dilated cardiomyopathy is a disease of left ventricular dysfunction accompanied
      by impairment of the beta1-adrenergic receptor (beta1-AR) signal cascade. The
      disturbed beta1-AR function may be based on an elevated sympathetic tone observed
      in patients with heart failure. Prolonged adrenergic stimulation may induce
      metabolic and electrophysiological disturbances in the myocardium, resulting in
      tachyarrhythmia that leads to the development of heart failure in human and
      sudden death. Hence, beta1-AR is considered as a promising drug target but
      attempts to develop effective and specific drug against this tempting
      pharmaceutical target is slowed down due to the lack of 3D structure of Homo
      sapiens beta1-AR (hsbetaADR1). This study encompasses elucidation of 3D
      structural and physicochemical properties of hsbetaADR1 via threading-based
      homology modeling. Furthermore, the docking performance of several docking
      programs including Surflex-Dock, FRED, and GOLD were validated by re-docking and
      cross-docking experiments. GOLD and Surflex-Dock performed best in re-docking and
      cross docking experiments, respectively. Consequently, Surflex-Dock was used to
      predict the binding modes of four hsbetaADR1 agonists. This study provides clear
      understanding of hsbetaADR1 structure and its binding mechanism, thus help in
      providing the remedial solutions of cardiovascular, effective treatment of asthma
      and other diseases caused by malfunctioning of the target protein. 

PMID- 25860350
TI  - Bed rest versus early ambulation with standard anticoagulation in the management
      of deep vein thrombosis: a meta-analysis.
AB  - INTRODUCTION: Bed rest has been considered as the cornerstone of management of
      deep vein thrombosis (DVT) for a long time, though it is not evidence-base, and
      there is growing evidence favoring early ambulation. METHODS: Electronic
      databases including Medline, PubMed, Cochrane Library and three Chinese databases
      were searched with key words of "deep vein thrombosis", "pulmonary embolism",
      "venous thrombosis", "bed rest", "immobilization", "mobilization" and
      "ambulation". We considered randomized controlled trials, prospective or
      retrospective cohort studies that compared the outcomes of acute DVT patients
      managed with early ambulation versus bed rest, in addition to standard
      anticoagulation. Meta-analysis pertaining to the incidence of new pulmonary
      embolism (PE), progression of DVT, and DVT related deaths were conducted, as well
      as the extent of remission of pain and edema. RESULTS: 13 studies were included
      with a total of 3269 patients. Compared to bed rest, early ambulation was not
      associated with a higher incidence of new PE, progression of DVT, or DVT related
      deaths (RD -0.03, 95% CI -0.05~ -0.02; Z = 1.24, p = 0.22; random effect model,
      Tau2 = 0.01). Moreover, if the patients suffered moderate or severe pain
      initially, early ambulation was related to a better outcome, with respect to
      remission of acute pain in the affected limb (SMD 0.42, 95%CI 0.09~0.74; Z =
      2.52, p = 0.01; random effect model, Tau2 = 0.04). Meta-analysis of alleviation
      of edema cannot elicit a solid conclusion because of significant heterogeneity
      among the few studies. CONCLUSIONS: Compared to bed rest, early ambulation of
      acute DVT patients with anticoagulation was not associated with a higher
      incidence of new PE, progression of DVT, and DVT related deaths. Furthermore, for
      the patients suffered moderate or severe pain initially, a better outcome can be
      seen in early ambulation group, regarding to the remission of acute pain in the
      affected limb.

PMID- 25860351
TI  - Correction: Development and host compatibility of plasmids for two important
      ruminant pathogens, mycoplasma bovis and mycoplasma agalactiae.

PMID- 25860352
TI  - River boats contribute to the regional spread of the dengue vector Aedes aegypti
      in the Peruvian Amazon.
AB  - BACKGROUND AND OBJECTIVES: The dramatic range expansion of the dengue vector
      Aedes aegypti is associated with various anthropogenic transport activities, but
      little is known about the underlying mechanisms driving this geographic
      expansion. We longitudinally characterized infestation of different vehicle types
      (cars, boats, etc.) to estimate the frequency and intensity of mosquito
      introductions into novel locations (propagule pressure). METHODS: Exhaustive
      adult and immature Ae. aegypti collections were performed on six different
      vehicle types at five ports and two bus/ taxi departure points in the Amazonian
      city of Iquitos, Peru during 2013. Aquatic vehicles included 32 large and 33
      medium-sized barges, 53 water taxis, and 41 speed boats. Terrestrial vehicles
      sampled included 40 buses and 30 taxis traveling on the only highway in the
      region. Ae. aegypti adult infestation rates and immature indices were analyzed by
      vehicle type, location within vehicles, and sampling date. RESULTS: Large barges
      (71.9% infested) and medium barges (39.4% infested) accounted for most of the
      infestations. Notably, buses had an overall infestation rate of 12.5%. On large
      barges, the greatest number of Ae. aegypti adults were found in October, whereas
      most immatures were found in February followed by October. The vast majority of
      larvae (85.9%) and pupae (76.7%) collected in large barges were produced in
      puddles formed in cargo holds. CONCLUSIONS: Because larges barges provide
      suitable mosquito habitats (due to dark, damp cargo storage spaces and ample
      oviposition sites), we conclude that they likely serve as significant
      contributors to mosquitoes' propagule pressure across long distances throughout
      the Peruvian Amazon. This information can help anticipate vector population
      mixing and future range expansions of dengue and other viruses transmitted by Ae.
      aegypti.

PMID- 25860353
TI  - Denitrification activity of a remarkably diverse fen denitrifier community in
      finnish lapland is N-oxide limited.
AB  - Peatlands cover more than 30% of the Finnish land area and impact N2O fluxes.
      Denitrifiers release N2O as an intermediate or end product. In situ N2O emissions
      of a near pH neutral pristine fen soil in Finnish Lapland were marginal during
      gas chamber measurements. However, nitrate and ammonium fertilization
      significantly stimulated in situ N2O emissions. Stimulation with nitrate was
      stronger than with ammonium. N2O was produced and subsequently consumed in gas
      chambers. In unsupplemented anoxic microcosms, fen soil produced N2O only when
      acetylene was added to block nitrous oxide reductase, suggesting complete
      denitrification. Nitrate and nitrite stimulated denitrification in fen soil, and
      maximal reaction velocities (vmax) of nitrate or nitrite dependent
      denitrification where 18 and 52 nmol N2O h-1 gDW-1, respectively. N2O was below
      30% of total produced N gases in fen soil when concentrations of nitrate and
      nitrite were <500 MUM. vmax for N2O consumption was up to 36 nmol N2O h-1 gDW-1.
      Denitrifier diversity was assessed by analyses of narG, nirK/nirS, and nosZ
      (encoding nitrate-, nitrite-, and nitrous oxide reductases, respectively) by
      barcoded amplicon pyrosequencing. Analyses of ~14,000 quality filtered sequences
      indicated up to 25 species-level operational taxonomic units (OTUs), and up to
      359 OTUs at 97% sequence similarity, suggesting diverse denitrifiers.
      Phylogenetic analyses revealed clusters distantly related to publicly available
      sequences, suggesting hitherto unknown denitrifiers. Representatives of species
      level OTUs were affiliated with sequences of unknown soil bacteria and
      Actinobacterial, Alpha-, Beta-, Gamma-, and Delta-Proteobacterial sequences.
      Comparison of the 4 gene markers at 97% similarity indicated a higher diversity
      of narG than for the other gene markers based on Shannon indices and observed
      number of OTUs. The collective data indicate (i) a high denitrification and N2O
      consumption potential, and (ii) a highly diverse, nitrate limited denitrifier
      community associated with potential N2O fluxes in a pH-neutral fen soil. 

PMID- 25860355
TI  - Genome-wide methylation patterns in Salmonella enterica Subsp. enterica Serovars.
AB  - The methylation of DNA bases plays an important role in numerous biological
      processes including development, gene expression, and DNA replication. Salmonella
      is an important foodborne pathogen, and methylation in Salmonella is implicated
      in virulence. Using single molecule real-time (SMRT) DNA-sequencing, we sequenced
      and assembled the complete genomes of eleven Salmonella enterica isolates from
      nine different serovars, and analysed the whole-genome methylation patterns of
      each genome. We describe 16 distinct N6-methyladenine (m6A) methylated motifs,
      one N4-methylcytosine (m4C) motif, and one combined m6A-m4C motif. Eight of these
      motifs are novel, i.e., they have not been previously described. We also
      identified the methyltransferases (MTases) associated with 13 of the motifs. Some
      motifs are conserved across all Salmonella serovars tested, while others were
      found only in a subset of serovars. Eight of the nine serovars contained a unique
      methylated motif that was not found in any other serovar (most of these motifs
      were part of Type I restriction modification systems), indicating the high
      diversity of methylation patterns present in Salmonella. 

PMID- 25860357
TI  - [Coverage of the gallbladder cancer prevention strategy in Chile: results from
      the 2009-2010 National Health Survey].
AB  - BACKGROUND: In Chile, gallbladder cancer (GBC) is one of the most important
      causes of death and gallstone disease (GSD) is its main risk factor. Abdominal
      ultrasonography (AU) is used for the diagnosis of GSD and cholecystectomy is used
      to prevent it. AIM: To estimate GSD prevalence in the general population and to
      assess the diagnostic and therapeutic coverage of GSD as a preventive strategy
      for GBC in Chile. MATERIAL AND METHODS: A standardized digestive symptoms
      questionnaire of the 2009-2010 Chilean National Health Survey was answered by
      5412 adults over 15 years old. Self-reports of AU, GBD and cholecystectomies were
      recorded. RESULTS: The prevalence of biliary-type pain was 7.1%. During the last
      five years, the prevalence of AU was 16%. GSD was reported in 20% of these tests
      and 84% of them were asymptomatic. The prevalence of AU was significantly lower
      in Araucania region and among people with less than 12 years of education. Life
      cholecystectomy prevalence was 11% and reached 40% in people aged over 60 years.
      Women accounted for 75% of total cholecystectomies. Twenty-one percent of
      individuals who referred biliary-type pain, were studied with an AU. Only 60% of
      people with GSD confirmed by AU underwent a cholecystectomy. CONCLUSIONS: GSD
      affects at least 27% of the Chilean adult population. Important deficits and
      inequities in GSD diagnostic and therapeutic coverage were identified.

PMID- 25860356
TI  - [Survival among renal allograft recipients from non related living donors].
AB  - BACKGROUND: There is a gap between the number of patients requiring a renal
      allograft and the number of potential deceased donors (DD). One alternative is
      using allografts from non-related living donors (NRLD). AIM: To compare survival
      and complications of renal allograft recipients from DD, related living donors
      (RLD) and NRLD. MATERIAL AND METHODS: Observational study of a cohort of renal
      allograft recipients. Of 253 transplants performed in a Chilean region between
      1981 and 2003, 20 patients received and allograft from a NRLD. Graft and patient
      survival of these patients were compared with those of 93 patients receiving an
      allograft from a related living donor and 140 receiving it from a DD. Patients
      were followed for 10 years or until death or dialysis requirement. RESULTS: No
      significant differences between groups in graft and patient survival, deaths with
      a functioning graft or return to dialysis were observed. Receptors of DD had more
      hospital admissions during the first years after receiving the graft, usually due
      to infections. Also a delayed graft function was more common among them.
      Glomerular filtration rate ten years after the graft was similar among the three
      groups. CONCLUSIONS: No differences in graft or patient survival was observed
      between patients receiving a renal allograft from NRLD, RLD or DD.

PMID- 25860354
TI  - Biomarkers of inflammation and axonal degeneration/damage in patients with newly
      diagnosed multiple sclerosis: contributions of the soluble CD163 CSF/serum ratio
      to a biomarker panel.
AB  - BACKGROUND: Expression of soluble CD163 (sCD163), a macrophage/microglia
      biomarker, is increased in inflammatory conditions, and sCD163 levels in the
      cerebrospinal fluid (CSF) have recently been shown to be elevated in patients
      with multiple sclerosis (MS): the sCD163 CSF/serum ratio was elevated in patients
      with relapsing-remitting MS (RRMS), primary progressive MS (PPMS), and clinically
      isolated syndrome (CIS) compared with symptomatic controls. OBJECTIVE: To
      investigate the contributions of the sCD163 CSF/serum ratio to a biomarker panel
      focusing on inflammation and axonal degeneration in newly diagnosed MS; thus
      optimising a diagnostic biomarker panel for MS. METHODS: After a full MS
      diagnostic work-up, including collection of paired samples of CSF and serum, 125
      patients were included in this study. Patients were divided into groups based on
      their diagnosis, and patients with normal clinical and paraclinical findings were
      defined as symptomatic controls. Serum and CSF levels, ratios, and indices of
      sCD163, CXCL13, osteopontin, neopterin, and CSF levels of neurofilament light
      polypeptide were determined by enzyme-linked immunosorbent assays (ELISAs). For
      sCD163 the results constitute a post-hoc analysis of already published data.
      RESULTS: All tested biomarkers, notably the sCD163 ratio, the CXCL13 ratio, the
      NEO ratio, the CSF level of NfL, the IgG index, and the serum level of OPN, were
      significantly correlated to RRMS, PPMS, and/or CIS. The individual biomarkers in
      single tests had a lower performance than the IgG index, however, their combined
      receiver operating characteristic (ROC) curve demonstrated excellent diagnostic
      discriminatory power. CONCLUSION: The biomarker panel showed distinct profiles
      for each patient group and could be a valuable tool for clinical differentiation
      of MS subgroups. The combined ROC analysis showed that sCD163 contributes
      positively as a diagnostic marker to a panel of established MS biomarkers.
      Patients with PPMS were demonstrated to have significantly elevated levels of
      both inflammatory and degenerative markers.

PMID- 25860358
TI  - [Bone mineral metabolism in patients with chronic kidney disease on dialysis in
      Southern Metropolitan Santiago].
AB  - BACKGROUND: Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) is a
      condition of dialysis patients associated with both morbidity and mortality.
      Management is based on clinical guidelines with goals that are hard to comply
      with. AIM: To describe and compare biochemical variables associated with this
      disorder in two different time periods. MATERIAL AND METHODS: Revision of medical
      records of 814 patients (49% females) dialyzed during 2009 and 1018 patients (48%
      females), dialyzed during 2012 in Southern Metropolitan Santiago. Information
      about serum calcium, phosphorus, parathyroid hormone (PTH) and albumin was
      retrieved. RESULTS: Median PTH values in 2009 and 2012 were 222.5 and 353.5 pg/ml
      respectively (p < 0.05). The figures for serum calcium corrected by albumin were
      9.0 and 8.5 mg/dl respectively (p < 0.05). The figures for phosphorus were 4.7
      and 5.0 mg/dl respectively (p < 0.05). The Calcium x Phosphorus product was 41.4
      and 42.5 mg2/dl2 (p < 0.05). Of note, the proportion patients with serum calcium
      below recommended levels (< 8.4 mg/dl) increased from 16% to 40% from 2009 to
      2012. The proportion of patients with biochemical variables within recommended
      ranges was lower in 2012 than in 2009. CONCLUSIONS: There was a low proportion of
      patients with bone metabolism parameters within ranges recommended by clinical
      guidelines. These parameters were worst in 2012.

PMID- 25860359
TI  - [Introduction of virtual patients to clinical case portfolios for undergraduate
      medical students].
AB  - BACKGROUND: In 2007, a Clinical-Case-Portfolio (CCP) was introduced as a new
      assessment instrument for fourth grade undergraduate medical students. Since
      then, several changes have been implemented such as reduction on the number of
      clinical cases, peer review and the introduction of virtual patient to the
      portfolio. AIM: To describe the virtual patient model incorporated to the CCP and
      assess the perception of this change and its effects on the performance of
      undergraduate students. MATERIAL AND METHODS: Virtual patients were implemented
      based on prototype clinical cases with specific syndromes. Students? perceptions
      about CCP before and after the introduction of virtual patients were evaluated
      using a validated questionnaire that was answered voluntarily and anonymously.
      RESULTS: Overall perception of CCP significantly improved after the incorporation
      of virtual patients (97.1 +/- 24.9 and 111.3 +/- 25.7 points; 57.8 and 66.2%
      respectively). The same improvements were observed for the domains ?Student
      Learning?, ?Organization and Evaluation?, ?Teaching Methodology? and
      ?Integration?. In both years, students obtained high grades in CCP evaluations.
      However CCP grades were not significantly correlated with integrated final
      grades. CONCLUSIONS: The incorporation of virtual patients improved undergraduate
      students? perception of CCP.

PMID- 25860360
TI  - [Clinical features of Guillain-Barre syndrome in 41 patients admitted to a public
      hospital].
AB  - BACKGROUND: Guillain-Barre syndrome (GBS) is the commonest cause of acute flaccid
      paralysis worldwide, with an incidence of 0.6-4 per 100.000 inhabitants per year.
      It affects all age groups and carries an incapacity burden of up to 20%. AIM: To
      describe the features of GBS in adult Chilean patients admitted to a tertiary
      care hospital. MATERIAL AND METHODS: Review of medical records of 41 patients
      aged 17 to 81 years (30 males) admitted to a public hospital with the diagnosis
      of GBS between 2003 and 2009. According to clinical and electrophysiological
      criteria, the patients were classified into different varieties of GBS. RESULTS:
      The incidence of GBS was higher in males (2.7:1) and the demyelinated GBS variety
      was found in 66% of cases. According to the Hughes? disability score, patients
      treated with plasmapheresis, showed non-statistically significant better outcomes
      than those treated with intravenous immunoglobulin. CONCLUSIONS: In this group of
      patients the demyelinated variety of GBS was more common than the axonal type.
      Although not statistically significant, the better response to plasmapheresis is
      encouraging and should prompt a controlled study.

PMID- 25860361
TI  - [Surgical treatment of renal hyperparathyroidism. Experience in 71 patients].
AB  - BACKGROUND: Surgery is an effective method for the management of renal
      hyperparathyroidism. AIM: To report the clinical presentation and results of
      surgical treatment of renal hyperparathyroidism. MATERIAL AND METHODS:
      Retrospective analysis of 58 patients aged 46 +/- 11 years with secondary
      hyperparathyroidism (HPT2) and 13 patients aged 53 +/- 11 years with tertiary
      hyperparathyroidism (HPT3), operated at a clinical hospital. RESULTS: In 55 cases
      (77.4%) the indications for surgery were complications of excess parathyroid
      hormone (PTH) and in 16 patients (22.6%) a failure of medical treatment. Total
      parathyroidectomy with intraoperative measurement of PTH (PTHop) plus a forearm
      parathyroid autograft was performed in 54 (93.1%) patients with HPT2 and in all
      patients with HPT3. PTHop decreased >= 75% in 51 patients (88%) with HPT2 and in
      9 patients (69.2%) with HPT3, respectively. Cure of the disease was achieved in
      52 (89.7%) and 11 (84.6%) patients with HPT2 and 3, respectively. Median follow
      up was 41 months. Five (9.6%) patients with HPT2 and two patients (18.2%) with
      HPT3 had a recurrence of the disease. CONCLUSIONS: In patients with renal
      hyperparathyroidism, the primary indication for surgery was the presence of
      complications of PTH excess. A drop in PTHop >= 75% from baseline predicts
      healing in 98% and 100% of cases with secondary or tertiary HPT respectively.
      Surgery was a safe and effective treatment in both groups.

PMID- 25860363
TI  - [Prevalence and risk factors for urinary incontinence among women consulting in
      primary care].
AB  - BACKGROUND: It is important to determine the relative importance of urinary
      incontinence in terms of its prevalence and how it affects the quality of life of
      women. AIM: To characterize urinary incontinence and factors associated with it
      in women aged over 30 years. MATERIAL AND METHODS: A survey about urinary
      incontinence and associated factors was answered by 289 women aged 30 to 81
      years, attending a public primary care clinic. RESULTS: The prevalence of urinary
      incontinence was 62.2%, and it was significantly associated with obesity,
      diabetes and a history of episiotomy. CONCLUSIONS: The high prevalence of urinary
      incontinence should prompt the implementation of public health measures to
      prevent and treat it effectively.

PMID- 25860362
TI  - [Benign focal liver lesions detected by computed tomography: Review of 1,184
      examinations].
AB  - BACKGROUND: Multidetector computed tomography (MDCT) of the abdomen, with use of
      contrast medium, is able to detect and differentiate most focal liver lesions.
      AIM: To determine the prevalence and features of benign focal liver lesions
      (BFLL) detected by abdominal MDCT. PATIENTS AND METHODS: We reviewed the reports
      of contrast abdominal MDCT performed to outpatients between August 2011 and July
      2012. Clinical data of examined patients and imaging findings in terms of
      description of the hepatic parenchyma and the presence of BFLL, were recorded.
      RESULTS: Data from 1,184 studies were analyzed. Of these, 461 studies (38.4%)
      reported BFLL. The most prevalent lesions were simple cysts in 290 studies (24%)
      and hemangiomas in 61 studies (5.1%), granuloma-calcification in 39 (3.2%), focal
      nodular hyperplasia in 19 (1.6%) and one adenoma. If patients with known causes
      of liver disease were excluded, the prevalence of BFLL did not change
      substantially (lesions were found in 396 (37.5%) patients). Compared with livers
      with signs of damage, normal livers had more cystic lesions (27 and 16.2%
      respectively, p = 0.014) and hemangiomas (5.3 and 1.1% respectively, p = 0.043).
      CONCLUSIONS: BFLL are very common findings in MDCT studies. Most of these lesions
      are simple cysts and hemangiomas.

PMID- 25860364
TI  - [Assessment of a version adapted and translated into Spanish of the Quality of
      Life Bipolar Disorder Questionnaire].
AB  - BACKGROUND: The Quality of life Bipolar Disorder (QoL.BD) Questionnaire
      specifically measures quality of life in patients with bipolar disorder. AIM: To
      adapt a version translated into Spanish of the questionnaire and assess its
      validity in Chilean patients. MATERIAL AND METHODS: The QoL. BD was adapted to
      the Chilean population through the back-translation method and then administered
      to 32 adult patients with a bipolar disorder and 31 subjects without the disease,
      both groups with similar socioeconomic status. To confirm the diagnosis, the
      International Neuropsychiatric Interview (MINI), Young (YMRS) and Hamilton (HAM
      D) scales were applied. Quality of life was assessed using the SF-36v.2 survey.
      We determined internal consistency, reliability, convergent validity, the cut-off
      point, and the sensibility and specificity of the scale. RESULTS: The Chilean
      version of the Questionnaire [QoL. BD-CL] had a high reliability (alpha = 0.95)
      and a high validity in reference to external criteria (correlation coefficients
      with SF-36 ranging from 0.453 and 0.819; p < 0.01). A cut-off point of 170, with
      sensitivity of 87.9% and specificity of 80% was determined. CONCLUSIONS: QoL.BD
      CL has adequate psychometric properties, as well as an adequate sensitivity and
      specificity to distinguish between negative and positive perceptions of life
      quality in Chilean patients with bipolar disorders.

PMID- 25860365
TI  - [Advances in the treatment of castration-resistant prostate cancer: emphasis in
      new hormonal therapies].
AB  - Prostate cancer represents the second cancer-related cause of death in North
      American and Chilean men. The main treatment for incurable stages of disease is
      surgical or pharmacological castration. However, with time and despite the
      addition of anti-androgens, the disease progresses to a clinical state that has
      been commonly referred to as ?hormone refractory?. In recent years, the concept
      of hormone refractoriness has been challenged and replaced by ?castration
      resistance?, acknowledging that further and optimal hormonal manipulation can be
      attained, beyond achieving testosterone levels at castration range. The purpose
      of this review is to summarize the recent therapeutic breakthroughs in the
      management of metastatic castrate resistant prostate cancer (mCRPC), with greater
      emphasis in the newer hormonal therapy agents such as Abiraterone and
      Enzalutamide. Future combination and sequential treatment strategies are
      contextualized in the current era of personalized cancer medicine and genomic
      characterization of prostate cancer. 

PMID- 25860366
TI  - [A reform proposal to strengthen public health care].
AB  - Currently, there is no discussion on the need to improve and strengthen the
      institutional health care modality of FONASA (MAI), the health care system used
      by the public services net and by most of the population, despite the widely
      known and long lasting problems such as waiting lists, hospital debt with
      suppliers, lack of specialists and increasing services purchase transference to
      the private sector, etc. In a dichotomous sectorial context, such as the one of
      health?s social security in Chile (the state on one side and the market on the
      other), points of view are polarized and stances tend to seek refuge within
      themselves. As a consequence, to protect the public solution is commonly
      associated with protecting the ?status quo?, creating an environment that is
      reluctant to change. The author proposes a solution based on three basic core
      ideas, which, if proven effective, can strengthen each other if combined
      properly. These are: network financing management, governance of health care
      services in MAI and investments and human resources in networked self-managed
      institutions. The proposal of these core ideas was done introducing a reality
      testing that minimizes the politic complexity of their implementation. 

PMID- 25860367
TI  - [Evaluation of public and private health care systems].
AB  - BACKGROUND: There is a great degree of dissatisfaction with the Chilean health
      care system. AIM: To investigate which are the most relevant perceived factors
      when the health care system is evaluated. MATERIAL AND METHODS: Analysis of a
      survey about the Chilean health care system carried out during 2011, 2012 and
      2013, involving 2,801 respondents. RESULTS: The response capacity of emergency
      systems was the main factor considered for the evaluation of public and private
      health care systems. Respondents who were affiliated to private insurance systems
      also took into consideration the quality of medical infrastructure. CONCLUSIONS:
      There are different factors considered when public or private health care systems
      are evaluated.

PMID- 25860368
TI  - [History of the University of Chile Faculty of Medicine and clinical hospital
      location].
AB  - The history of the location of the University of Chile Faculty of Medicine North
      Campus is derived from a farm of Pedro de Valdivia founder of the city of
      Santiago de la Nueva Extremadura and governor of the ?Reyno de Chile?. This work
      narrates succinctly the history of this particular location from the Spanish
      Conquest period to present days. 

PMID- 25860369
TI  - [Orbital emphysema after Valsalva maneuver. Report of one case].
AB  - Orbital emphysema is a rare complication of orbital and facial trauma, involving
      the sinuses and occasionally the nasal cavity. Most cases occur as a result of
      trauma but spontaneous orbital emphysema has been reported. Clinical
      manifestations are often delayed until the upper airway pressure increases as
      when blowing or coughing. Along with the fracture, the rupture of the underlying
      mucosa is essential for emphysema to manifest. We report a 29-years-old male who
      consulted in the emergency room due to eyelid swelling after a Valsalva maneuver,
      a couple of hours after suffering a facial injury secondary to a fall. In the
      presence of eyelid emphysema, the patient underwent craniofacial imaging studies,
      confirming an ethmoidal lamina papyracea fracture. 

PMID- 25860370
TI  - [Secondary acute myeloid leukemia in a lung allograft recipient. Report of one
      case].
AB  - Secondary acute myeloid leukemia is a very rare complication in patients with
      solid organ transplantation. We report a 62 years old female who received a right
      single lung allograft for idiopathic pulmonary fibrosis. Her immunosuppression
      scheme consisted in prednisone, azathioprine, and tacrolimus. Two years after the
      transplantation, she presented with progressive pancytopenia. Bone marrow
      aspiration was informed as a M4 acute myeloid leukemia, confirmed by flow
      cytometry. Cytogenetic study was complex, including alterations in chromosome 5.
      A secondary acute myeloid leukemia was diagnosed. The patient developed
      nosocomial pneumonia and died a few days after the diagnosis, without specific
      treatment. The pathogenesis of acute myeloid leukemia is probably related to the
      intensive exposure to immunosuppressant, especially azathioprine, in these
      patients. 

PMID- 25860371
TI  - [Diabetes mellitus and hypertension: the relevance of checking albuminuria].

PMID- 25860372
TI  - [Moral distress, Health Care Systems and the teaching of health care personnel].

PMID- 25860373
TI  - CKD in disadvantaged populations.

PMID- 25860375
TI  - Application of wavelet transform for PDZ domain classification.
AB  - PDZ domains have been identified as part of an array of signaling proteins that
      are often unrelated, except for the well-conserved structural PDZ domain they
      contain. These domains have been linked to many disease processes including
      common Avian influenza, as well as very rare conditions such as Fraser and Usher
      syndromes. Historically, based on the interactions and the nature of bonds they
      form, PDZ domains have most often been classified into one of three classes
      (class I, class II and others - class III), that is directly dependent on their
      binding partner. In this study, we report on three unique feature extraction
      approaches based on the bigram and trigram occurrence and existence
      rearrangements within the domain's primary amino acid sequences in assisting PDZ
      domain classification. Wavelet packet transform (WPT) and Shannon entropy denoted
      by wavelet entropy (WE) feature extraction methods were proposed. Using 115
      unique human and mouse PDZ domains, the existence rearrangement approach yielded
      a high recognition rate (78.34%), which outperformed our occurrence
      rearrangements based method. The recognition rate was (81.41%) with validation
      technique. The method reported for PDZ domain classification from primary
      sequences proved to be an encouraging approach for obtaining consistent
      classification results. We anticipate that by increasing the database size, we
      can further improve feature extraction and correct classification. 

PMID- 25860376
TI  - Clinical pharmacokinetics and pharmacodynamics of the endothelin receptor
      antagonist macitentan.
AB  - Pulmonary arterial hypertension (PAH) is a progressive disease of the lung
      vascular system, which leads to right-sided heart failure and ultimately death if
      untreated. Treatments to regulate the pulmonary vascular pressure target the
      prostacyclin, nitric oxide, and endothelin (ET) pathways. Macitentan, an oral,
      once-daily, dual ETA and ETB receptor antagonist with high affinity and sustained
      receptor binding is the first ET receptor antagonist to show significant
      reduction of the risk of morbidity and mortality in PAH patients in a large-scale
      phase III study with a long-term outcome. Here we present a review of the
      available clinical pharmacokinetic, pharmacodynamic,
      pharmacokinetic/pharmacodynamic relationship, and drug-drug interaction data of
      macitentan in healthy subjects, patients with PAH, and in special populations. 

PMID- 25860378
TI  - Histopathology and prognosis of de novo bladder tumors following solid organ
      transplantation.
AB  - BACKGROUND: Patients following solid organ transplantation have an increased risk
      of developing de novo bladder tumors, but their biology is poorly characterized.
      METHODS: We studied 1743 patients who underwent a transurethral resection of a
      newly diagnosed bladder tumor at a single institution. The histopathology,
      treatment, recurrence-free survival and overall survival were evaluated and
      compared between transplant and non-transplant patients. RESULTS: We identified
      74 transplant patients who developed a de novo bladder tumor after a median post
      transplantation interval of 62 months. The tumor was malignant in 29 patients (39
      %). The most common benign lesion was nephrogenic adenoma (84 %), which neither
      coexisted with nor developed into malignant tumors during follow-up. Compared
      with non-transplant patients (n = 1669), transplant patients were significantly
      younger (median 55 vs 69 years, P < 0.001) and had a 9.0-fold higher odds of
      benign tumors (P < 0.001), while there were no differences in pathology among
      patients with urothelial carcinoma of the bladder (UCB). In a multivariable
      analysis for non-muscle-invasive UCB that was adjusted for the risk group,
      patients with a transplant had a 1.8-fold increased risk of recurrence (P =
      0.048). Four of five transplant patients did not respond to Bacillus Calmette
      Guerin instillations. There were no differences in overall survival after radical
      cystectomy (P = 0.87). CONCLUSIONS: The majority of bladder tumors in transplant
      patients are benign, and they neither coexist with nor develop into malignant
      tumors. Transplant patients with non-muscle-invasive UCB show an increased risk
      of disease recurrence, while those treated with radical cystectomy have similar
      outcomes to patients without a transplant.

PMID- 25860379
TI  - Controversial evidence for the use of HistoScanningTM in the detection of
      prostate cancer.
AB  - INTRODUCTION: Given the growing body of literature since first description of
      HistoScanningTM in 2008, there is an unmet need for a contemporary review.
      EVIDENCE ACQUISITION: Studies addressing HistoScanningTM in prostate cancer (PCa)
      were considered to be included in the current review. To identify eligible
      reports, we relied on a bibliographic search of PubMed database conducted in
      January 2015. EVIDENCE SYNTHESIS: Twelve original articles were available to be
      included in the current review. The existing evidence was reviewed according to
      the three following topics: prediction of final pathology at radical
      prostatectomy, prediction of disease stage and application at prostate biopsy.
      CONCLUSIONS: High sensitivity and specificity for HistoScanningTM to predict
      cancer foci >=0.5 ml at final pathology were achieved in the pilot study. These
      results were questioned, when HistoScanningTM derived tumor volume does not
      correlate with final pathology results. Additionally, HistoScanningTM was not
      able to provide reliable staging information according to neither extraprostatic
      extension, nor seminal vesicle invasion prior to radical prostatectomy.
      Controversy data also exist according to the use of HistoScanningTM at prostate
      biopsy. Specifically, most encouraging results were recorded in a small patient
      cohort. Conversely, HistoScanningTM achieved poor prediction of positive
      biopsies, when relying on larger studies. Finally, the combination of
      HistoScanningTM and conventional ultrasound achieved lower detection rates than
      systematic biopsy. Currently, evidence is at best weak and questions whether
      HistoScanningTM might improve the detection of PCa.

PMID- 25860380
TI  - A rapid, highly accurate method for quantifying CALR mutant allele burden in
      persons with myeloproliferative neoplasms.
AB  - BACKGROUND: Calreticulin (CALR) mutations were recently identified in a
      substantial proportion of persons with essential thrombocythemia (ET) and with
      primary myelofibrosis (PMF) without JAK2(V617F). Consequently rapid, sensitive,
      and specific methods to detect and quantify these mutations are needed. METHODS:
      We studied samples from 1088 persons with myeloproliferative neoplasms (MPNs)
      including 421 JAK2(V617F) negative subjects with ET, PMF, polycythemia vera (PV),
      chronic myeloid leukemia (CML) and hyper-eosinophilic syndrome (HES). Detection
      of CALR exon 9 mutations was done by PCR amplification followed by fragment
      length analysis and direct sequencing. Dilution assays were used to determine
      CALR mutant allele burden. RESULTS: We detected CALR mutations in blood and bone
      marrow samples from 152 subjects with ET and with PMF but not in samples from
      normal or persons with PV, CML, or HES. CALR mutant peaks were distinct from wild
      type peaks and dilution experiments indicated a sensitivity level of 0.5-5% for a
      CALR mutant allele in a wild-type background. Diverse types of mutations were
      detected including deletions, insertions, and complex indels. All mutations were
      confirmed by direct sequencing. We also used dilution experiments to quantify
      mutant allele burden. We were able to reproducibly detect mutant allele levels as
      low 5% (0.5-5%) in a wild-type background. CONCLUSIONS: PCR amplification
      followed by fragment length analysis is a rapid, sensitive, and specific method
      for screening persons with MPNs for CALR mutations, especially those with ET and
      PMF and for estimating mutant allele burden.

PMID- 25860381
TI  - Model-based acceleration of look-locker T1 mapping.
AB  - Mapping the longitudinal relaxation time T1 has widespread applications in
      clinical MRI as it promises a quantitative comparison of tissue properties across
      subjects and scanners. Due to the long scan times of conventional methods,
      however, the use of quantitative MRI in clinical routine is still very limited.
      In this work, an acceleration of Inversion-Recovery Look-Locker (IR-LL) T1
      mapping is presented. A model-based algorithm is used to iteratively enforce an
      exponential relaxation model to a highly undersampled radially acquired IR-LL
      dataset obtained after the application of a single global inversion pulse. Using
      the proposed technique, a T1 map of a single slice with 1.6mm in-plane resolution
      and 4mm slice thickness can be reconstructed from data acquired in only 6s. A
      time-consuming segmented IR experiment was used as gold standard for T1 mapping
      in this work. In the subsequent validation study, the model-based reconstruction
      of a single-inversion IR-LL dataset exhibited a T1 difference of less than 2.6%
      compared to the segmented IR-LL reference in a phantom consisting of vials with
      T1 values between 200ms and 3000ms. In vivo, the T1 difference was smaller than
      5.5% in WM and GM of seven healthy volunteers. Additionally, the T1 values are
      comparable to standard literature values. Despite the high acceleration, all
      model-based reconstructions were of a visual quality comparable to fully sampled
      references. Finally, the reproducibility of the T1 mapping method was
      demonstrated in repeated acquisitions. In conclusion, the presented approach
      represents a promising way for fast and accurate T1 mapping using radial IR-LL
      acquisitions without the need of any segmentation. 

PMID- 25860377
TI  - Impact of Genetic Polymorphisms of ABCB1 (MDR1, P-Glycoprotein) on Drug
      Disposition and Potential Clinical Implications: Update of the Literature.
AB  - ATP-binding cassette transporter B1 (ABCB1; P-glycoprotein; multidrug resistance
      protein 1) is an adenosine triphosphate (ATP)-dependent efflux transporter
      located in the plasma membrane of many different cell types. Numerous
      structurally unrelated compounds, including drugs and environmental toxins, have
      been identified as substrates. ABCB1 limits the absorption of xenobiotics from
      the gut lumen, protects sensitive tissues (e.g. the brain, fetus and testes) from
      xenobiotics and is involved in biliary and renal secretion of its substrates. In
      recent years, a large number of polymorphisms of the ABCB1 [ATP-binding cassette,
      sub-family B (MDR/TAP), member 1] gene have been described. The variants 1236C>T
      (rs1128503, p.G412G), 2677G>T/A (rs2032582, p.A893S/T) and 3435C>T (rs1045642,
      p.I1145I) occur at high allele frequencies and create a common haplotype;
      therefore, they have been most widely studied. This review provides an overview
      of clinical studies published between 2002 and March 2015. In summary, the effect
      of ABCB1 variation on P-glycoprotein expression (messenger RNA and protein
      expression) and/or activity in various tissues (e.g. the liver, gut and heart)
      appears to be small. Although polymorphisms and haplotypes of ABCB1 have been
      associated with alterations in drug disposition and drug response, including
      adverse events with various ABCB1 substrates in different ethnic populations, the
      results have been majorly conflicting, with limited clinical relevance. Future
      research activities are warranted, considering a deep-sequencing approach, as
      well as well-designed clinical studies with appropriate sample sizes to elucidate
      the impact of rare ABCB1 variants and their potential consequences for effect
      sizes.

PMID- 25860383
TI  - A Genetically Encoded FRET Sensor for Intracellular Heme.
AB  - Heme plays pivotal roles in various cellular processes as well as in iron
      homeostasis in living systems. Here, we report a genetically encoded fluorescence
      resonance energy transfer (FRET) sensor for selective heme imaging by employing a
      pair of bacterial heme transfer chaperones as the sensory components. This heme
      specific probe allows spatial-temporal visualization of intracellular heme
      distribution within living cells. 

PMID- 25860382
TI  - Bovine herpesvirus 1 regulatory proteins are detected in trigeminal ganglionic
      neurons during the early stages of stress-induced escape from latency.
AB  - Bovine herpesvirus 1 (BHV-1) establishes latency in sensory neurons. The
      synthetic corticosteroid dexamethasone consistently induces reactivation from
      latency. Within 90 min after latently infected calves are treated with
      dexamethasone, two BHV-1 regulatory proteins, BHV-1-infected cell protein 0
      (bICP0) and viral protein 16 (VP16), are expressed in the same neuron. In this
      study, we demonstrate that VP16 and bICP0 can be detected at 22 and 33 min after
      dexamethasone (DEX) treatment of latently infected calves. However, we were
      unable to discern whether VP16 or bICP0 was expressed at early times after
      reactivation. VP16+ neurons consistently express the glucocorticoid receptor
      suggesting corticosteroid-mediated activation of its receptor rapidly stimulates
      reactivation from latency.

PMID- 25860384
TI  - Selective Cryolysis of Sebaceous Glands.
AB  - Acne vulgaris is a nearly universal cutaneous inflammatory disease. Excess sebum
      production is an integral part of disease pathogenesis. Medical therapies that
      reduce sebum excretion result in clinical improvement of acne. Given the
      preferential susceptibility of lipid-containing cells to cold, we investigated
      the hypothesis that controlled local skin cooling causes preferential injury to
      sebaceous glands, in murine and swine models using a range of temperatures as low
      as -10  degrees C, and then on the backs of human subjects. In mouse ears, peak
      histologic damage occurred 72 hours after treatment; eosinophilic necrotic plugs
      formed within sebaceous glands, and the number of glands was significantly
      reduced up to 1 week post treatment. Cooling disrupted sebocyte cell membranes,
      alkaline phosphatase activity, and significantly reduced sebocyte lipid content.
      In human volunteers, cooling damaged sebaceous glands and reduced sebum output
      for 2 weeks, with minimal injury to surrounding tissues. Selective cryolysis of
      sebaceous glands is achievable through brief, non-invasive skin cooling,
      suggesting that controlled cooling could be developed as an effective treatment
      for acne vulgaris. 

PMID- 25860386
TI  - Myelodysplasia Cutis Versus Leukemia Cutis.

PMID- 25860385
TI  - Roles of GasderminA3 in Catagen-Telogen Transition During Hair Cycling.
AB  - Hair follicles undergo cyclic behavior through regression (catagen), rest
      (telogen), and regeneration (anagen) during postnatal life. The hair cycle
      transition is strictly regulated by the autonomous and extrinsic molecular
      environment. However, whether there is a switch controlling catagen-telogen
      transition remains largely unknown. Here we show that hair follicles cycle from
      catagen to the next anagen without transitioning through a morphologically
      typical telogen after Gsdma3 mutation. This leaves an ESLS (epithelial strand
      like structure) during the time period corresponding to telogen phase in WT mice.
      Molecularly, Wnt10b is upregulated in Gsdma3 mutant mice. Restoration of Gsdma3
      expression in AE (alopecia and excoriation) mouse skin rescues hair follicle
      telogen entry and significantly decreases the Wnt10b-mediated Wnt/beta-catenin
      signaling pathway. Overexpression of Wnt10b inhibits telogen entry by increasing
      epithelial strand cell proliferation. Subsequently, hair follicles with a Gsdma3
      mutation enter the second anagen simultaneously as WT mice. Hair follicles cannot
      enter the second anagen with ectopic WT Gsdma3 overexpression. A luciferase
      reporter assay proves that Gsdma3 directly suppresses Wnt signaling. Our findings
      suggest that Gsdma3 has an important role in catagen-telogen transition by
      balancing the Wnt signaling pathway and that morphologically typical telogen is
      not essential for the initiation of a new hair cycle. 

PMID- 25860387
TI  - Morphological characters are compatible with mitogenomic data in resolving the
      phylogeny of nymphalid butterflies (lepidoptera: papilionoidea: nymphalidae).
AB  - Nymphalidae is the largest family of butterflies with their phylogenetic
      relationships not adequately approached to date. The mitochondrial genomes
      (mitogenomes) of 11 new nymphalid species were reported and a comparative
      mitogenomic analysis was conducted together with other 22 available nymphalid
      mitogenomes. A phylogenetic analysis of the 33 species from all 13 currently
      recognized nymphalid subfamilies was done based on the mitogenomic data set with
      three Lycaenidae species as the outgroups. The mitogenome comparison showed that
      the eleven new mitogenomes were similar with those of other butterflies in gene
      content and order. The reconstructed phylogenetic trees reveal that the
      nymphalids are made up of five major clades (the nymphaline, heliconiine,
      satyrine, danaine and libytheine clades), with sister relationship between
      subfamilies Cyrestinae and Biblidinae, and most likely between subfamilies
      Morphinae and Satyrinae. This whole mitogenome-based phylogeny is generally
      congruent with those of former studies based on nuclear-gene and mitogenomic
      analyses, but differs considerably from the result of morphological cladistic
      analysis, such as the basal position of Libytheinae in morpho-phylogeny is not
      confirmed in molecular studies. However, we found that the mitogenomic phylogeny
      established herein is compatible with selected morphological characters
      (including developmental and adult morpho-characters). 

PMID- 25860388
TI  - A new mutation in exon 2 of the bone morphogenetic protein 15 gene is associated
      with increase in prolificacy of Mehraban and Lori sheep.
AB  - Some mutations in bone morphogenetic protein 15 (BMP15) gene have been known to
      be associated with prolificacy in various breeds of sheep. Polymorphism of BMP15
      gene exon 2 was studied in 100 Mehraban and 100 Lori ewes, using PCR-SSCP and DNA
      sequencing methods. A new point mutation (G -> A) was found at position 57 of the
      amplified 312-b fragment of BMP15 gene exon 2. The frequencies of the AG and GG
      genotypes were 69.4 and 30.6 % in Mehraban and 44.7 and 55.3 % in Lori ewes,
      respectively. No individual carrying the AA genotype was found in the studied
      population. The allelic frequencies for A and G alleles were 34.7 and 65.3 % in
      Mehraban and 22.4 and 77.6 % in Lori ewes, respectively. Average litter size in
      the AG genotype (1.56) was significantly (P < 0.01) higher than the GG ewes
      (1.08). The results of the present study indicated the potential of the observed
      SNP in exon 2 of BMP15 for further exploitation in marker-assisted selection to
      improve reproduction efficiency of Mehraban and Lori sheep. 

PMID- 25860389
TI  - Aggregation of a Tetrasaccharide Acceptor Observed by NMR: Synthesis of
      Pentasaccharide Fragments of the Le(a)Le(x) Tumor-Associated Hexasaccharide
      Antigen.
AB  - We report the synthesis of a tetrasaccharide and two pentasaccharide fragments of
      the Le(a)Le(x) tumor-associated carbohydrate antigen alpha-L-Fuc-(1->4)-[beta-D
      Gal-(1->3)]-beta-D-GlcNAc-(1->3)-beta-D-Gal-(1->4)-[alpha-L-Fuc-(1->3)]-beta-D
      GlcNAc-(1->OR). The choice of protecting groups permitted a one-step global
      deprotection (Na/NH3(l)). The protected chlorohexyl glycoside pentasaccharide was
      the precursor to the hexyl glycoside, to be used as a soluble inhibitor, and the
      aminohexyl glycoside analogue, to be conjugated to proteins for surface
      immobilization and immunization experiments. We observed that a linear
      tetrasaccharide that contained two N-acetylglucosamine residues and a free OH
      group gave two distinct sets of (1)H NMR signals when the data were acquired in
      deuterated chloroform. Data acquisition at variable concentrations and variable
      temperatures suggests that the second set of NMR signals results from aggregation
      of the tetrasaccharide driven by the formation of intermolecular H-bonds
      involving the NHAc. While the formation of intra- and intermolecular H-bonds
      involving N-acetylgucosamine residues has been reported in non-H-bonding
      solvents, this is, to our knowledge, the first time that these have lead to the
      appearance of two distinct sets of signals in the NMR spectra. This aggregation
      may explain the lack of reactivity observed when an attempt is made to
      glycosylate such an acceptor using non-H-bonding solvents such as
      dichloromethane.

PMID- 25860390
TI  - Emergence of a novel cluster of influenza A(H5N1) virus clade 2.2.1.2 with
      putative human health impact in Egypt, 2014/15.
AB  - A distinct cluster of highly pathogenic avian influenzaviruses of subtype A(H5N1)
      has been found to emergewithin clade 2.2.1.2 in poultry in Egypt since summer2014
      and appears to have quickly become predominant.Viruses of this cluster may be
      associated withincreased incidence of human influenza A(H5N1) infectionsin Egypt
      over the last months.

PMID- 25860391
TI  - Emergence of tick-borne encephalitis in new endemic areas in Austria: 42 years of
      surveillance.
AB  - Human infections with tick-borne encephalitis (TBE)virus are a public health
      concern in certain regions of Europe, central and eastern Asia. Expansions of
      endemic areas and increased incidences have been associated with different
      factors including ecological changes supporting tick reproduction, socioeconomic
      changes increasing human outdoor activities and climatic changes favouring virus
      circulation in natural foci. Austria is among the most strongly affected
      countries in Central Europe, but the annual number of cases has strongly declined
      due to vaccination. Here,we have analysed changes of the incidence of TBE in the
      unvaccinated population of all federal states of Austria over a period of 42
      years. The overall incidence in Austria has remained constant, but new strongly
      affected endemic regions have emerged in alpine valleys in the west of Austria.
      In parallel, the incidence in low-land regions in the north-east of the country
      is decreasing. There is no evidence for a shift to higher altitudes of infection
      sites in the traditional TBE zones,but the average altitudes of some newly
      established endemic areas in the west are significantly higher. Our analyses
      underscore the focal nature of TBE endemic areas and the potential of TBE virus
      to emerge in previously unaffected regions.

PMID- 25860392
TI  - Survey of surveillance systems and select prevention activities for hepatitis B
      and C, European Union/European Economic Area, 2009.
AB  - Hepatitis B and C viral infections are leading causes of hepatic cirrhosis and
      cancer. The incidence and prevalence of both hepatitis B and C varies across
      European countries. European wide surveillance data help to understand the
      dynamic epidemiology of hepatitis B and C, which is important for the
      implementation and effectiveness of prevention and control activities.Comparison
      of surveillance data between countries in Europe is hampered by the differences
      in national healthcare and reporting systems. This report presents the results of
      a survey in 2009 which was undertaken to collect baseline information on
      surveillance systems and core prevention programmes for hepatitis B and C in
      individual European Union/ European Economic Area countries. The results provide
      key information to aid the interpretation of surveillance data, and while
      indicating heterogeneity in national surveillance systems and programmes, they
      highlight the potential of these systems. This resource has supported the
      implementation of a standardised European enhanced surveillance programme.

PMID- 25860393
TI  - Lower seroreactivity to European than to North American H3N2 swine influenza
      viruses in humans, Luxembourg, 2010.
AB  - Seroreactivity to H3N2 swine influenza viruses (SIVs)was evaluated in serum
      samples collected from 843 people aged 0 to 100 years in 2010 in Luxembourg.Sera
      were analysed by haemagglutination inhibition(HI) and virus neutralisation (VN)
      assays targeting a European H3N2 SIV, a North American H3N2 variant of swine
      origin (H3N2v) and human seasonal H3N2 viruses isolated in 1975, 1995 and 2005.
      HI antibodies(titre >= 10) against European H3N2 SIV were almost exclusively
      detected in those born before 1990, of whom 70% were seropositive. HI antibodies
      against H3N2v were predominantly found in those born before 2000, with 86%
      seropositive. Titres against the North American H3N2v were higher than against
      the European H3N2 SIV. VN patterns were similar, but with higher rates and
      titres. We also demonstrated lower seroreactivity to European H3N2 SIV than to
      North American H3N2v virus. Finally, we found a strong correlation between HI
      titres against the European H3N2SIV and H3N2v and their respective human
      ancestors,A/Victoria/3/75 and A/Nanchang/933/95. This finding and the minimal
      contacts between humans and pigs in Luxembourg suggest that anti-SIV antibodies
      inhuman serum samples reflect serological cross-reactivity with historical human
      H3N2 viruses. Our findings help assess the pandemic risk of H3N2 SIV.

PMID- 25860394
TI  - Streptococcus pneumoniae nasopharyngeal colonisation in children aged under six
      years with acute respiratory tract infection in Lithuania, February 2012 to March
      2013.
AB  - serotypes among children in Lithuania are limited. A prospective study was
      carried out from February 2012 to March 2013 to evaluate the circulation of SPn
      serotypes among young children in five cities of Lithuania before the
      introduction of universal vaccination with pneumococcal conjugate vaccine (PCV).
      A total of 900 children under six years of age who presented to primary care
      centres or a hospital emergency department with acute respiratory tract infection
      (RTI) were enrolled in the study. The SPn colonisation rate was40.8% (367/900),
      with a peak at two and three years old(48.8% and 45.4%, respectively). Of the 367
      SPn isolates, the most common serotypes were 6B (15.8%,n = 58), 19F (13.9%, n =
      51), 23F (13.9%, n = 51), 15(10.1%, n = 37), 14 (9.5%, n = 35), 6A (9.3%, n=
      34),11 (4.6%, n = 17), 3 (3.0%, n = 11) and 18C (3.0%, n =11); less frequent were
      23 (non-23F) (2.7%, n = 10), 19A(2.2%, n = 8) and 9V (1.6%, n = 6). Serotypes 6A
      and 11 were more common in children under two years-old;18C was found only in
      children aged two to five years.The serotypes found might be an important
      predictor of the likely effectiveness of the PCVs currently available in
      Lithuania

PMID- 25860395
TI  - Letter to the editor: is a reduced duration of post-discharge surgical site
      infection surveillance really in our best interests?

PMID- 25860396
TI  - Authors response: is a reduced duration of post-discharge surgical site infection
      surveillance really in our best interests?

PMID- 25860400
TI  - Correction: recovery from an acute infection in C. elegans requires the GATA
      transcription factor ELT-2.

PMID- 25860401
TI  - Construction of mouse phantoms from segmented CT scan data for radiation
      dosimetry studies.
AB  - We present the complete construction methodology for an anatomically accurate
      mouse phantom made using materials which mimic the characteristics of tissue,
      lung, and bone for radiation dosimetry studies. Phantoms were constructed using 2
      mm thick slices of tissue equivalent material which was precision machined to
      clear regions for insertion of lung and bone equivalent material where
      appropriate. Images obtained using a 3D computed tomography (CT) scan clearly
      indicate regions of tissue, lung, and bone that match their position within the
      original mouse CT scan. Additionally, radiographic films are used with the
      phantom to demonstrate dose mapping capabilities. The construction methodology
      presented here can be quickly and easily adapted to create a phantom of any
      specific small animal given a segmented CT scan of the animal. These physical
      phantoms are a useful tool to examine individual organ dose and dosimetry within
      mouse systems that are complicated by density inhomogeneity due to bone and lung
      regions. 

PMID- 25860402
TI  - The effect of prophylactic migraine treatment on arterial stiffness.
AB  - BACKGROUND: Migraine is a common type of primary headache predominantly seen in
      women. This study aimed to evaluate endothelial function in patients with
      migraine using pulse wave velocity (PWV). METHODS: The study included 73 patients
      with newly diagnosed migraine and 80 healthy subjects. All patients and controls
      underwent baseline transthoracic echocardiography and PWV measurements. Patients
      were randomized to three groups to receive propranolol, flunarizine or
      topiramate, and the measurements were repeated at the end of 1 month. RESULTS:
      The newly diagnosed migraine patients and the control group exhibited no
      differences in baseline clinical characteristics, and the measurements showed
      that PWV was 7.4 +/- 1.0 m/s in the patient group and 6.0 +/- 1.0 m/s in the
      control group (p < 0.001). The same measurements were repeated during a control
      visit at the end of 1 month. Following treatment, a significant decrease was
      observed in PWV in all patient groups compared to baseline (p < 0.001). Subgroup
      analysis showed significantly decreased PWV in all drug groups, with the most
      prominent decrease in the topiramate group. CONCLUSIONS: The increased PWV
      demonstrated in migraine patients in this study stands out as an additional
      parameter elucidating endothelial dysfunction in these patients. Decreasing the
      number of migraine attacks with prophylactic treatment may reduce PWV and
      decrease cardiovascular risk in long-term follow-up.

PMID- 25860403
TI  - Thrombosis factors and oxidant/antioxidant markers in obese and hypertensive
      women during pregnancy.
AB  - OBJECTIVE: To investigate the oxidative profile and thrombotic markers in obese
      and hypertensive mothers. METHODS: Thirty obese, 28 hypertensive and 34 healthy
      control mothers were recruited from Tlemcen Hospital, Algeria. Plasma vitamin C,
      nitric oxide, superoxide anion, erythrocyte glutathione, malondialdehyde,
      carbonyl proteins and erythrocyte antioxidant enzyme activities and coagulation
      markers [protein C, protein S, fibrinogen, prothrombin, antithrombin, activated
      partial thromboplastin time (APTT), lupus anticoagulants (LACs)] were measured.
      Changes in plasma urea, creatinine, uric acid, glucose and lipid levels were also
      determined. RESULTS: Plasma glucose concentrations were high in obese mothers,
      and plasma urea, uric acid and creatinine levels were increased in hypertensive
      compared with healthy mothers. Obese and hypertensive mothers had low vitamin C
      and glutathione values, catalase and superoxide dismutase activities, and high
      triglyceride, superoxide anion, malondialdehyde and carbonyl protein levels
      compared with control mothers. Plasma nitric oxide levels were enhanced in obese
      mothers but reduced in hypertensive mothers. Fibrinogen and prothrombin levels
      were significantly enhanced in obese and hypertensive mothers. Protein C, protein
      S, antithrombin and APTT values were significantly higher in hypertensive
      mothers. Only hypertensive mothers were positive for LACs. CONCLUSION: Obese and
      hypertensive mothers presented oxidative stress and a pro-thrombotic state. Their
      oxidative and hemostasis profile should be carefully considered and appropriate
      management organized.

PMID- 25860404
TI  - Dengue haemorrhagic fever or dengue shock syndrome in children.
AB  - INTRODUCTION: Dengue haemorrhagic fever and dengue shock syndrome are major
      causes of hospital admission and mortality in children. METHODS AND OUTCOMES: We
      conducted a systematic review and aimed to answer the following clinical
      question: What are the effects of supportive treatments for dengue haemorrhagic
      fever or dengue shock syndrome in children? We searched: Medline, Embase, The
      Cochrane Library, and other important databases up to March 2014 (Clinical
      Evidence reviews are updated periodically, please check our website for the most
      up-to-date version of this review). We included harms alerts from relevant
      organisations such as the US Food and Drug Administration (FDA) and the UK
      Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found
      nine studies that met our inclusion criteria. We performed a GRADE evaluation of
      the quality of evidence for interventions. CONCLUSIONS: In this systematic review
      we present information relating to the effectiveness and safety of the following
      interventions: adding blood component transfusion to standard intravenous fluids;
      adding corticosteroids or intravenous immunoglobulin to standard intravenous
      fluids; and crystalloids versus colloids.

PMID- 25860405
TI  - Anisotropy effect of three-membered rings in (1)H NMR spectra: quantification by
      TSNMRS and assignment of the stereochemistry.
AB  - The spatial magnetic properties (through space NMR shieldings, TSNMRSs) of
      cyclopropane; of the heteroanalogous oxirane, thiirane, and aziridine; and of
      various substituted mono-, dis-, and tris-cyclic analogues have been computed by
      the GIAO perturbation method employing the nucleus independent chemical shift
      (NICS) concept and visualized as iso-chemical-shielding surfaces (ICSSs) of
      various size and direction. The TSNMRS values, thus obtained, can be employed to
      visualize the anisotropy (ring current) effect of the cyclopropane ring moiety.
      This approach has been employed to qualify and quantify substituent influences
      and contributions of appropriate ring heteroatoms O, NH, and S on the anisotropy
      (ring current) effect of three-membered ring moieties, and to assign the
      stereochemistry of mono-, bis-, and tris-cyclic structures containing
      cyclopropane as a structural element. Characteristic examples are included. 

PMID- 25860406
TI  - Asymmetric Synthesis of P-Stereogenic Phosphinic Amides via Pd(0)-Catalyzed
      Enantioselective Intramolecular C-H Arylation.
AB  - The palladium-catalyzed enantioselective intramolecular C-H arylation of N-(2
      haloaryl)-P,P-diphenylphosphinic amides furnishes P-stereogenic phosphine oxide
      derivatives in 61-99% yield with 88-97% ee. The catalyst generated in situ from a
      TADDOL-derived phosphoramide ligand and Pd(dba)2 is optimum in terms of yield and
      enantioselectivities. 

PMID- 25860407
TI  - HIV/AIDS and auditory function in adults: the need for intensified research in
      the developing world.
AB  - This article reviews published research on auditory function in HIV-infected
      adults, while also highlighting the need for intensified research on this topic
      in Africa. It begins with an introduction to the effects of HIV disease and
      treatment on the auditory system, and so highlights the need to put auditory
      function in adults with HIV or AIDS on the healthcare and research agenda in
      developing countries. The discussion refers to this population in regard to:
      published prevalence and incidence data related to auditory manifestations; most
      prevalent types of auditory manifestations and hearing loss; degree,
      configuration, and symmetry of the hearing loss; types of onset of hearing loss;
      and the proposed direct and indirect causes of auditory manifestations in HIV
      disease. Finally, the possible effects of HIV/AIDS drug treatments on the
      auditory system, as an indirect cause of hearing loss, are also discussed. A
      review of the literature revealed that auditory manifestations in adults with HIV
      or AIDS are heterogeneous in nature and are possibly due to various causes.
      Auditory presentations, including hearing loss, tinnitus and vertigo (in varied
      combinations) can occur with hearing loss, which includes conductive, mixed,
      sensorineural, and central types of hearing loss. The severity of hearing loss
      can range from mild to profound, occurring either unilaterally or bilaterally,
      with the types of onset including sudden or gradual and progressive. The varied
      causes of hearing loss include HIV infection or AIDS illness as a primary cause,
      opportunistic infections, and antiretroviral treatments. The studies discussed
      are mainly from developed countries where the presentation and management of HIV
      and AIDS can be different to that in developing countries because the context is
      different. This suggests a need for more research in this area since the numbers
      of adults living with HIV or AIDS in developing countries like South Africa is
      relatively high. 

PMID- 25860408
TI  - Understanding the experiences of doctors who undertake elective surgery on
      HIV/AIDS patients in an area of high incidence in South Africa.
AB  - This study investigates the experiences of doctors who perform elective surgical
      procedures in an area of South Africa with a high incidence of HIV and AIDS. A
      qualitative study approach was adopted. Interviews were individually conducted
      with 15 doctors. The transcribed interviews were read four times, each with a
      different data-collection purpose, and follow-up interviews were carried out when
      it was necessary to complete the data set. Surgical doctors from two semi-urban
      hospitals and one rural hospital in northern KwaZulu-Natal province took part in
      the study. The analysis of the interviews rendered four areas of concern in the
      experiences of doctors who perform surgery on HIV/ AIDS patients. These were:
      personal factors, patient factors, factors relating to the structure of the
      health system, and factors concerning protocols for the treatment of patients
      with HIV or AIDS. Although the doctors were altruistic in their approaches to
      operating on HIV/AIDS patients, they commonly mentioned the increased levels of
      stress they experience as a result of a multiplicity of issues surrounding the
      treatment and care of an HIV/AIDS patient specifically. The public health system
      has not made special arrangements to deal with the increased patient loads in
      hospitals as a result of the HIV epidemic, and this will have to be addressed as
      the number of HIV/AIDS patients increases. 

PMID- 25860409
TI  - South Africa youths' higher-risk sexual behaviour: an eco-developmental analysis.
AB  - Despite their high levels of knowledge about HIV and AIDS, young people ages 15
      24 years in South Africa remain disproportionately affected by the epidemic.
      Young people's continued susceptibility to HIV infection has been consistently
      linked to intractable higher-risk sexual behaviours. This paper uses multivariate
      techniques and secondary data from two nationally representative surveys to
      illuminate individual and socio-structural factors that play a significant role
      in youths' continued engagement in higher-risk behaviour, despite their high
      awareness about HIV and AIDS. The findings show that notwithstanding progress in
      terms of increased condom use and reduced incidence of other sexually transmitted
      infections, the average age of sexual debut remains low, multiple sexual
      partnerships are prevalent, and inconsistent condom use is widespread among young
      people. Factors significantly associated with these risk behaviours occur at the
      individual and structural levels and include issues of race, gender, poverty and
      susceptibility to peer pressure. The paper concludes by recommending that future
      HIV-prevention interventions in South Africa should aim at building resilience
      among youths by promoting affirmative, supportive interventions that emphasize
      the potentials of young people. 

PMID- 25860410
TI  - Adherence to antiretroviral therapy among HIV-infected children attending a donor
      funded clinic at a tertiary hospital in Nigeria.
AB  - The success of antiretroviral therapy (ART) depends on a high level of adherence
      to a life-long regimen of antiretroviral drugs (ARVs). Since the scale-up of
      access to ARVs in Nigeria, few studies have determined the level of adherence of
      ART among children. This study was undertaken to determine the level of ART
      adherence among paediatric patients at an outpatient clinic, the reasons for non
      adherence, and the factors associated with adherence, according to caregivers'
      reports. Out of a total of 212 children, 183 (86%) were adherent in the three
      days preceding the interview, while 29 (14%) were not adherent. Drug exhaustion
      at home (16 children), followed by 'child slept through' (7 children) and
      'caregiver away' were the most common reasons for a child having missed one or
      more ARV doses. Independent factors for adherence were male gender (odds ratio
      [OR] = 2.85; 95% confidence interval [CI]: 1.17-6.92) and attendance at last
      scheduled clinic appointment (OR = 4.76; 95% CI: 1.73-13.04). The caregiver's
      highest educational attainment, distance travelled to the clinic, use of
      medication reminders, formulation of ARVs, duration of HAART usage, age of the
      child and orphan status were not significantly associated with adherence to drug
      treatment. The overall level of adherence was high and similar to the rate
      reported prior to free access to ART services in Nigeria. Among child patients on
      HAART, there is a need to identify factors affecting clinic attendance and drug
      exhaustion at home. 

PMID- 25860411
TI  - Quality of life of people living with HIV/AIDS and on highly active
      antiretroviral therapy in Ethiopia.
AB  - The Amharic version of the Short Form-36 Health Survey (SF-36) was used to
      measure quality of life among patients on highly active antiretroviral therapy
      (HAART) at selected governmental hospitals in central and southern Ethiopia. The
      study was cross-sectional and used SF-36-specific software for automatic scoring
      of the form's scales and dimensions. Pearson bivariate correlations showed
      moderate correlation between the SF-36 scales, ranging from 0.2673 between
      'general health' and 'vitality,' to 0.8583 between 'role physical' and 'role
      emotional.' Cronbach's-alphawas >0.70 for six out of eight multi-item scales,
      with values ranging from 0.6500 to 0.8860 for all scales, thus indicating good
      internal reliability of the Amharic version of the SF-36. The independent
      variables shown to positively affect mean scores were: duration of treatment, CD4
      cell count, and adherence to doses of antiretrovirals. Participants treated for
      >12 months had higher mean scores for all domains than those who had been treated
      for <=12 months. Likewise, those with a CD4 cell count >200 cells/mm(3) had
      better mean scores for all scales except 'social functioning' and 'mental health'
      than those with counts <=200. Participants adhering to treatment (in the last 15
      days, according to self-report) had better mean scores for all scales except
      'role physical,' 'bodily pain' and 'vitality' in comparison to those who were not
      adherent. The findings suggest that the Amharic version of the SF-36 is a valid
      and reliable health survey instrument for use in Ethiopia to assess the quality
      of life of people living with HIV/AIDS on HAART. 

PMID- 25860412
TI  - Bereavement, silence and culture within a peer-led HIV/AIDS-prevention strategy
      for vulnerable children in South Africa.
AB  - In addressing the psychosocial effects of the HIV and AIDS pandemic among
      vulnerable children, the issue of bereavement appears inadequately addressed.
      Amid the global discourse on children orphaned and made vulnerable by HIV and
      AIDS, this paper explores how cultural contexts and social environments in South
      Africa shape children's experience of grief. The argument draws on a number of
      qualitative studies and uses empirical evidence from an evaluation of a peer-led
      HIV/AIDS-prevention strategy aimed at providing psychosocial support for 10- to
      13-year-old South African children living in resource-poor communities. The paper
      reveals a central paradox regarding how the intervention's objective of talking
      about death and eliciting memories of deceased loved ones with young children is
      confounded by cultural practices located in notions of silence and the need to
      protect children. The paper acknowledges the 'culture of silence' surrounding
      death in some African contexts, but concludes that peer-led strategies have the
      potential to naturally circumvent these cultural taboos, simultaneously creating
      a much-needed space for young children to cry and talk among themselves, even if
      remaining silent at home in the presence of adults. 

PMID- 25860413
TI  - Understanding self-appraisal of HIV-infection risk among young adults in Nigeria:
      evidence from a national survey.
AB  - A major component of HIV prevention is to encourage individuals to appreciate
      their personal risk of contracting the virus with the aim of encouraging them to
      take steps to reduce the risks. This article addresses the accuracy of an
      individual's risk assessment by matching this with individual's reported risk
      behaviours in order to assess possible congruence. Although the relationship
      between risk perception and risk behaviours has been studied by previous authors
      using cross-sectional studies, this has not been extensively studied using a
      large nationally representative data set, such as in Nigeria. In our attempt to
      address this, we classified HIV-risk behaviour into low-risk and high-risk
      behaviour. We considered both descriptive and inferential approaches in our
      analyses. The findings were triangulated with qualitative studies using focus
      group discussions conducted among members of the target group in Nigeria.
      Dependence of risk perception on some selected background characteristics,
      HIV/AIDS-knowledge indicators, experience of sexually transmitted infections
      (STIs), as well as exposure to the Society for Family Health (SFH) radio
      campaigns in Nigeria were investigated through multiple logistic regression
      models. Among the respondents with risk behaviours, being single, Christian,
      male, and listening to the SFH radio campaigns were associated with a higher
      perception of risk of contracting HIV. 

PMID- 25860414
TI  - Perceptions of HIV/AIDS leaders about faith-based organisations' influence on
      HIV/AIDS stigma in South Africa.
AB  - The extent of the HIV pandemic-particularly in the hardest-hit countries,
      including South Africa-has prompted a call for greater engagement of all groups,
      including faith-based organisations (FBOs). Although FBOs are known to play a
      substantial role in providing care and support to those affected by HIV and AIDS,
      empirical evidence in regard to their actions in the broader context of stigma is
      limited. A qualitative, key-informant survey was conducted in South Africa as
      part of a six-country international study to examine perceptions of how FBOs have
      contributed to reduction in HIV risk, vulnerability and related impacts. The
      special emphasis of this paper is the influence of FBOs on stigma and
      discrimination. In-depth interviews were held with 34 senior-level key informants
      who act as key decision-makers in the response to HIV and AIDS in South Africa.
      Secular and faith-based respondents shared their perceptions of the faith-based
      response, including FBOs' actions in relation to HIV/AIDS stigma and
      discrimination. Our study revealed that while FBOs were perceived as taking some
      action to address stigma in South Africa, FBOs were also thought to contribute to
      HIV/AIDS- discrimination through conflating issues of sexuality and morality, and
      through associating HIV and AIDS with sin. The interviewees indicated a number of
      internal and external challenges faced by FBOs to deal effectively with stigma,
      including lack of information and skills, the difficulty of maintaining
      confidentiality in health services, and self-stigmatisation which prevents HIV
      infected persons from revealing their status. Findings from this study may help
      both faith-based and secular groups capitalise on the perceived strengths of FBOs
      as well as to elucidate their perceived weaknesses so that these areas of concern
      can be further explored and addressed. 

PMID- 25860415
TI  - HIV and AIDS vulnerability in fishing communities in Mangochi district, Malawi.
AB  - The fisheries sector contributes significantly to Malawi's national economy and
      to the livelihoods of the poor as certain activities in the sector have
      relatively low barriers to entry. Various studies have shown that the fisheries
      sector suffers from high HIV prevalence in many low-income countries. In Malawi,
      HIV prevalence as well as the causes and impact of HIV infections among
      fisherfolk are yet to be assessed. Participatory action research was conducted in
      Mangochi District, in the southern part of Lake Malawi, between December 2007 and
      January 2008, to identify critical HIV-risk points along the value-chain for the
      Lake Sardine or usipa (Engraulicypris sardella) fishery. Data were collected
      through interviews with key informants and from focus group discussions at the
      community, institution, district and market levels. An analysis of vulnerability
      resulted in the formulation of mechanisms to redress HIV and AIDS prevention and
      mitigation at each point of vulnerability. The findings show that HIV and AIDS
      vulnerability in the fishery's market-chain is highest where fish processing and
      trading influence sexual relationships between fishermen and female fish traders.
      The period of high usipa catches (December to March) coincides with a period of
      food shortage and fishing offers income-generating opportunities for many food
      insecure households. This increases competition in processing and trading fish, a
      socio-economic situation that may result in increased instances of transactional
      sex. The interactions along the usipa fishery's market-chain, from rural to urban
      settings, also favour the transmission of HIV from areas of high prevalence to
      areas with otherwise low HIV risk. 

PMID- 25860416
TI  - Challenging power and meaning: outlining the popular epidemiology of HIV and AIDS
      in Rakai, Uganda, c. 1975-1990.
AB  - This article traces the historical evolution of conditions that favoured the
      spread of HIV in Rakai district, Uganda, and the process of evolution of the
      local, popular epidemiology of HIV and AIDS. It argues that the HIV epidemic was
      made possible by economic and social disparities, which grew more pronounced
      since the mid-1970s as a result of economic decline, physical insecurity, and the
      disbanding of public services. The local constructions of AIDS in Rakai have
      changed and shifted according to the progress of the epidemic, eventually
      challenging the initial cultural construction of the disease, based on local
      notions about causality between disease and morality. The progress of the
      epidemic undermined the local intellectual authority (e.g. traditional healers,
      health workers, and religious leaders), creating a need to produce additional
      explanations of the disease. The concept of 'Slim' in Rakai emerged as a popular
      construct to denote the physical, psychological and social consequences of HIV
      disease. The concept reflects popular concerns over the outcomes of the epidemic
      rather than its cause, being more concerned about the fate of individuals and
      communities than about issues of morality. Later, the moral construction of
      'Slim' that accompanied the biomedical categorisation of AIDS as a sexually
      transmitted disease made it appear as a disease of sexual indulgence and
      promiscuity. The bio-moral construction of 'Slim' was also challenged by local
      evangelical claims about the power of faith and morality to regenerate its
      'victims,' something that biomedicine had not been able to provide. As the
      disease has become part of the social ecology of Rakai and the rest of Uganda,
      interpretations of it will continue to be challenged and reconstructed. 

PMID- 25860417
TI  - Implementation of the national programme for prevention of mother-to-child
      transmission of HIV: a rapid assessment in Cacadu district, South Africa.
AB  - To conduct a rapid assessment of the prevention-of-mother-to-child-transmission
      of-HIV (PMTCT) programme in two of the three local service areas in Cacadu
      district, Eastern Cape province, South Africa, we designed an exploratory study
      using a mixed-methods approach. Quantitative and qualitative data on PMTCT
      programme implementation were collected in 2008 through a structured assessment
      at the 44 health facilities implementing the programme in the province. This
      included in-depth interviews with 11 clinic supervisors, 31 clinic programme
      coordinators, and 8 hospital/maternity staff members in order to examine their
      perceived problems and suggestions regarding PMTCT programme implementation; an
      assessment of the clinic registers and recording systems; a meeting with
      stakeholders; and one feedback meeting with clinic managers, sub-district
      management and other stakeholders in regard to the results of the rapid
      assessment. Overall, most of the national criteria for PMTCT programme
      implementation were fulfilled across the health facilities. However, shortcomings
      were found relating to health policy, health services delivery and clients'
      health-seeking behaviour. The findings show the need for a well-functioning
      health system with adequate and trained staff, a reduced staff workload, proper
      case recording, an improved patient follow-up system, better support for staff,
      the empowerment of PMTCT clients, strong leadership, and coordination and
      collaboration between partners. 

PMID- 25860418
TI  - Will you leave me too?: The impact of father absence on the treatment of a 10
      year-old girl.
AB  - This paper addresses the impact father absence has on child development and the
      nature of the transference between father absent, child and therapist. A review
      of psychoanalytic concepts and theories that relate to this topic are applied to
      a case study of a preadolescent girl with an incarcerated father. Specific forms
      of transference that occurred between the client and her male therapist are
      articulated in an effort to demonstrate the power of working in the transference
      with girls who struggle with their feelings about having an absent father. 

PMID- 25860419
TI  - Knowledge and experiences of child care workers regarding care and management of
      children with special needs in Gauteng, South Africa.
AB  - OBJECTIVE: The aim of the study was to determine the knowledge and experiences of
      child care workers in the care and management of children with special needs in
      four institutions of the Department of Social Development in Tshwane Metro.
      METHOD: Self-administered questionnaires were used to collect data from 253 child
      care workers. RESULTS: Child care workers showed a low level of knowledge about
      children with special needs. Most of the participants (67.4%) indicated that they
      need training in the care and management of children with special needs. Over
      half of the participants (57.3%) experienced feelings of frustration associated
      with working with special needs children. Lack of training and resources, and
      children's level of disability and behaviour were the major causes of this
      frustration. CONCLUSIONS: A system of care to assure safe, quality service is
      paramount to ensure optimum care and management of children with special needs.

PMID- 25860420
TI  - Xhosa male initiation: freedom of choice versus the need to belong.
AB  - BACKGROUND: The question of choice and individual decision making in groups where
      a strong ideology exists has been repeatedly studied and debated. The objective
      of this paper is to highlight the aspects of influence pertaining to initiation
      in the life world of the Xhosa boy. The amaXhosa are speakers of Bantu languages
      traditionally living in south-east South-Africa, and in the last two centuries
      throughout the southern and central-southern parts of the country. METHOD: To
      substantiate the literature study, a survey in the form of a questionnaire was
      done to establish the attitudes of Xhosa people regarding traditional male
      initiation. To gather in-depth information from persons who had personal contact
      with initiates, interviews were conducted with two selected people in helping
      professions. DISCUSSION: The author argues that the traditional custom of male
      initiation among the amaXhosa rests on an ideology that tolerates no dissent or
      critique and that deprives individuals of their decision-making power. It is
      further argued that the implication of not undergoing the ritual is so severe for
      Xhosa boys that the choice they are thought to have may not be a choice in
      practice. CONCLUSIONS: Questions were raised regarding the role of children and
      women in general in a patriarchal society. As an example of culture and religion
      as influencing factors in a group's reality, Xhosa male initiation was discussed.
      These arguments call for the raising of questions and identifying themes and
      discourse in the area of children's right to choice. RESULTS: The results
      indicate that, regardless of physical and psychological implications, the custom
      in its traditional form is still preferred by most respondents.

PMID- 25860421
TI  - A comparison of peer and non-peer exposure to unwanted early sexual experiences
      among students in South Africa and Belgium.
AB  - OBJECTIVE: This study examined peer and non-peer unwanted early sexual
      experiences (UESE) among 3,689 university students to establish whether peer UESE
      is as coercive and bothersome as non-peer UESE. METHOD: A self-report checklist
      was administered to all consenting students attending an orientation programme at
      one South African (SA) and one Belgian university. RESULTS: Of the respondents
      21% indicated that they had UESE before their 16th birthday (39.2% SA and 13.5%
      Belgians). Of respondents indicating UESE, 22.4% (173) reported that they had
      UESE with a person where the age difference was greater than 5 years and 54.2%
      (418) reported UESE with an age difference less than 5 years. Overall, a
      statistically significant difference was found between peer exposed and non-peer
      exposed groups at the time the UESE occurred related to bothersomeness of the
      UESE. SA men and women experienced more psychological pressure or physical force
      among the non-peer exposed group than the peer exposed group.

PMID- 25860423
TI  - Winnicott's children.

PMID- 25860422
TI  - Sexual abstinence and HIV knowledge in school-going adolescents with intellectual
      disabilities and non-disabled adolescents in Nigeria.
AB  - OBJECTIVE: The study compared sexual practices and predictors of sexual
      abstinence among adolescent learners with mild/moderate intellectual impairments
      and their non-disabled peers in Nigeria. METHOD: This was a comparative, cross
      sectional survey that assessed sexual practices of learners with mild/moderate
      intellectual impairments (N = 300) and non-disabled learners (N = 300), aged 12
      19 years, in Oyo State, Nigeria. Data were analysed using SPSS 15.0. RESULTS:
      Findings indicated that learners with mild/moderate intellectual impairments
      abstained from sex less than non-disabled adolescents (p = 0.002). Girls with
      intellectual disabilities were almost four times more likely to report history of
      rape than non-disabled girls. There was no significant difference between
      sexually abstinent and sexually experienced learners with intellectual
      disabilities (p = 0.671) and non-disabled adolescents (p = 0.181) in their mean
      HIV transmission knowledge scores. Many factors, including being male, social
      supports and self-efficacy determined sexual abstinence among adolescents.
      CONCLUSIONS: Although sexual abstinence is the recommended HIV-prevention
      strategy in HIV prevention curriculum in Nigerian schools, findings of this study
      suggested that sexual abstinence alone may not be effective for adolescent
      learners with intellectual disabilities. Interventions targeting youth with
      intellectual disabilities should consider all these factors.

PMID- 25860424
TI  - The thinking heart: Three levels of psychoanalytic therapy with disturbed
      children.

PMID- 25860425
TI  - The origins, prevention and treatment of infant crying and sleeping problems: An
      evidence based guide for healthcare professionals and the families they support.

PMID- 25860426
TI  - Journal abstracts from current research in the field of child and adolescent
      mental health.

PMID- 25860427
TI  - Super High Dosing with a Novel Buttiauxella Phytase Continuously Improves Growth
      Performance, Nutrient Digestibility, and Mineral Status of Weaned Pigs.
AB  - This study was conducted to evaluate the efficacy of a novel Buttiauxella phytase
      to pigs fed P-deficient, corn-soybean meal diets. One hundred and twenty
      crossbred piglets (9.53 +/- 0.84 kg) were allocated to one of five treatments
      which consisted of four low P diets (0.61 % Ca and 0.46 % total P) supplemented
      with 0, 500, 1,000, or 20,000 FTU/kg phytase as well as a positive control diet
      (0.77 % Ca and 0.62 % total P). Each treatment had six replicated pens with four
      pigs per pen. Pigs were fed the experimental diets for 28 days. Phytase
      supplementation linearly improved (P < 0.05) average daily gain (ADG), feed
      conversion ratio (FCR), and apparent total tract digestibility (ATTD) of dry
      matter, gross energy, crude protein, Ca, and P in weaned pigs. Super high dosing
      with phytase (20,000 FTU/kg) further increased (P < 0.05) ADG compared with 500
      FTU/kg phytase inclusion group, as well as ATTD of Ca and P. Metacarpal bone
      characteristics and several trace mineral concentration in bone, plasma, or organ
      tissues were linearly (P < 0.05) improved at increasing dose of phytase. Super
      high dosing with phytase (20,000 FTU/kg) supplementation improved (P < 0.05) Mn
      and Zn concentration in bone compared to normal dose of phytase supplementation
      (500 or 1,000 FTU/kg). In conclusion, supplementation of 500 FTU of Buttiauxella
      phytase/kg and above effectively hydrolyzed phytate in a low-P corn-soybean diet
      for pigs. In addition, a super high dosing with phytase (20,000 FTU/kg) improved
      macro- or micro mineral availability and growth performance. 

PMID- 25860428
TI  - Hippocampal BDNF content in response to short- and long-term exercise.
AB  - The hippocampus is a region in the brain that is crucial for learning and memory.
      Previous researches proved that brain-derived neurotrophic factor (BDNF) is a
      probable responsible protein in the learning and memory formation process. BDNF
      content is thought to be affected by environmental enrichment and physical
      activity. The purpose of this research was to identify the effect of short- and
      long-term forced exercise on hippocampal BDNF levels. A total of 30 Wistar rats
      were randomly divided into three groups (control, short-term exercise and long
      term exercise) and treated by treadmill running based on their group. As the
      treadmill running period finished, the animals were anesthetized. The hippocampus
      was dissected out immediately and BDNF content of the samples was assessed by
      ELISA. None of the exercise paradigms did make any significant change on
      hippocampal BDNF levels. Although exercise was proposed to up-regulate BDNF
      levels, these results show that the intensity or the duration of running paradigm
      used in forced exercise protocols here was not enough to affect BDNF levels in
      the hippocampus significantly. 

PMID- 25860429
TI  - Quantitative Magnetic Resonance Venography is Correlated With Intravenous
      Pressures Before and After Venous Sinus Stenting: Implications for Treatment and
      Monitoring.
AB  - BACKGROUND: Endovascular stenting is an effective treatment for patients with
      clinically significant cerebral venous sinus stenosis. Traditionally, stenting is
      indicated in elevated intravenous pressures on conventional venography; however,
      noninvasive monitoring is more desirable. Quantitative magnetic resonance
      angiography is an imaging modality that measures blood flow noninvasively.
      Established in the arterial system, applications to the venous sinuses have been
      limited. OBJECTIVE: To examine quantitative magnetic resonance venography (qMRV)
      in the measurement of venous sinus flow in patients undergoing endovascular
      stenting and to identify a relationship with intravenous pressures. METHODS: Five
      patients with intracranial hypertension secondary to venous sinus stenosis
      underwent cerebral venous stenting between 2009 and 2013 at a single institution.
      Preoperatively, venous sinus flow was determined by using qMRV, and intravenous
      pressure was measured during venography. After stenting, intravenous pressure,
      qMRV flow, and clinical outcomes were assessed and compared. RESULTS: A mean
      prestenotic intravenous pressure of 45.2 mm Hg was recorded before stenting,
      which decreased to 27.4 mm Hg afterward (Wilcoxon signed rank test P = .04).
      Total jugular outflow on qMRV increased by 260.2 mL/min. Analysis of the change
      in intravenous pressure and qMRV flow identified a linear relationship (Pearson
      correlation r = 0.926). All patients displayed visual improvement at 6 weeks.
      CONCLUSION: Venous outflow by qMRV increases after endovascular stenting and
      correlates with significantly improved intravenous pressures. These findings
      introduce qMRV as a potential adjunct to measure venous flow after stenting, and
      as a plausible tool in the selection and postoperative surveillance of the
      patient who has cerebral venous sinus stenosis.

PMID- 25860430
TI  - Surgery for Unruptured Spetzler-Martin Grade 3 Brain Arteriovenous Malformations:
      A Prospective Surgical Cohort.
AB  - BACKGROUND: There is uncertainty regarding the management of unruptured Spetzler
      Martin grade 3 brain arteriovenous malformations (SMG3 ubAVM). OBJECTIVE: To
      analyze our series of patients treated by surgery. METHODS: A single-surgeon
      database of consecutively enrolled bAVMs (between 1989 and 2014) was analyzed.
      Adverse outcomes due to surgery were assigned within the first 6 weeks following
      surgery and outcome was prospectively recorded and assigned at the last follow-up
      visit by using modified Rankin Scale (mRS) score. RESULTS: Of the 137 reviewed
      patients, 112 (82%) were treated by surgery, 15 (11%) were treated elsewhere or
      by radiosurgery, and 10 (7%) were recommended for conservative management.
      Surgery for SMG3 ubAVM was associated with adverse outcomes with a new permanent
      neurological deficit of mRS >1 in 23 of 112 (21%) patients. Permanent
      neurological deficit leading to a mRS >2 from surgery was 3.6% (95% confidence
      interval, 1.1%-9.1%). Late recurrence of a bAVM occurred in 3 of 103 (2.9%)
      patients who had complete obliteration of bAVM confirmed immediately after
      surgery and who were subsequently later followed with radiological studies during
      the mean follow-up period of 3.0 years (range, 6 days to 18.8 years). CONCLUSION:
      When discussing surgical options for SMG3 ubAVM, a thorough understanding of the
      significance and incidence of adverse events and outcomes is required to fully
      inform patients. For our series, the additional subclassification of SMG ubAVM
      (based on variables contributing to the SMG or age) would not have been of use.

PMID- 25860431
TI  - The Expression of DNMT1 in Pathologic Scar Fibroblasts and the Effect of 5-aza-2
      Deoxycytidine on Cytokines of Pathologic Scar Fibroblasts.
AB  - OBJECTIVE: This study aimed to investigate the expression and significance of DNA
      methyltransferase 1 (DNMT1) in pathologic scar fibroblasts, as well as the
      influence of methylase inhibitor, 5-aza-2-deoxycytidine, on pathological scars.
      MATERIAL AND METHODS: Samples of 31 keloids, 20 hypertrophic scars, and 25 normal
      skins were taken to test the expression rate of DNMT1 by immunohistochemistry.
      Primary fibroblasts were cultured with the monoplast method. Samples were
      categorized into the keloid group (K group), 5-aza-2-deoxycytidine keloid
      intervention group (K+ group), normal skin group (N group), hypertrophic scar
      group (H group), and 5-aza-2-deoxycytidine hypertrophic scar intervention group
      (H+ group). The expressions of DNMT1, transforming growth factor-beta (TGF-beta),
      and Smad7 mRNA in each group were detected with realtime polymerase chain
      reaction. The effect of 5-aza-2-deoxycytidine on the cell cycle and apoptosis of
      pathologic scar fibroblasts were analyzed with flow cytometry. RESULTS: The
      expression rate of DNMT1 was 100% in keloid fibroblasts, 90% in hyperplastic scar
      fibroblasts, and 8% in normal skin fibroblasts. After the intervention with 5-aza
      2-deoxycytidine in the K+ group, the expression of DNMT1 and TGF-beta1 mRNA was
      lower, Smad7 mRNA was elevated in pathological scar fibroblasts, the flow
      cytometry showed the proportion of cells in G0/G1 phase were increased, and the
      proportion of apoptosis cells were also increased, with similar changes in the
      cells in the H and H+ groups. CONCLUSION: DNMT1 may play a vital role on the
      generation of pathological scars. Methylaze inhibitors 5-aza-2-deoxycytidine may
      influence the related cytokines of pathological scars, inhibit proliferation, and
      promote apoptosis of pathological scar fibroblasts. The generation of
      pathological scars may be related with methylation of certain genes. 5-aza-2
      deoxycytidine be a new choice for the treatment of pathological scars.

PMID- 25860432
TI  - A label-free fluorescence assay for potassium ions using riboflavin as a G
      quadruplex ligand.
AB  - A label-free fluorescence K(+) assay was developed using riboflavin, a new G
      quadruplex ligand, and a G-quadruplex sequence (PW17). 

PMID- 25860433
TI  - Multiple factors affect diversity and abundance of ammonia-oxidizing
      microorganisms in iron mine soil.
AB  - Ammonia oxidation by microorganisms is a critical process in the nitrogen cycle.
      In this study, four soil samples collected from a desert zone in an iron
      exploration area and others from farmland and planted forest soil in an iron mine
      surrounding area. We analyzed the abundance and diversity of ammonia-oxidizing
      archaea (AOA) and ammonia-oxidizing bacteria (AOB) in iron-mining area near the
      Miyun reservoir using ammonia monooxygenase. A subunit gene (amoA) as molecular
      biomarker. Quantitative polymerase chain reaction was applied to explore the
      relationships between the abundance of AOA and AOB and soil physicochemical
      parameters. The results showed that AOA were more abundant than AOB and may play
      a more dominant role in the ammonia-oxidizing process in the whole region. PCR
      denaturing gradient gel electrophoresis was used to analyze the structural
      changes of AOA and AOB. The results showed that AOB were much more diverse than
      AOA. Nitrosospira cluster three constitute the majority of AOB, and AOA were
      dominated by group 1.1b in the soil. Redundancy analysis was performed to explore
      the physicochemical parameters potentially important to AOA and AOB. Soil
      characteristics (i.e. water, ammonia, organic carbon, total nitrogen, available
      phosphorus, and soil type) were proposed to potentially contribute to the
      distributions of AOB, whereas Cd was also closely correlated to the distributions
      of AOB. The community of AOA correlated with ammonium and water contents. These
      results highlight the importance of multiple drivers in microbial niche formation
      as well as their affect on ammonia oxidizer composition, both which have
      significant consequences for ecosystem nitrogen functioning. 

PMID- 25860434
TI  - Re-alignment of the unmapped reads with base quality score.
AB  - MOTIVATION: Based on the next generation genome sequencing technologies, a
      variety of biological applications are developed, while alignment is the first
      step once the sequencing reads are obtained. In recent years, many software tools
      have been developed to efficiently and accurately align short reads to the
      reference genome. However, there are still many reads that can't be mapped to the
      reference genome, due to the exceeding of allowable mismatches. Moreover, besides
      the unmapped reads, the reads with low mapping qualities are also excluded from
      the downstream analysis, such as variance calling. If we can take advantages of
      the confident segments of these reads, not only can the alignment rates be
      improved, but also more information will be provided for the downstream analysis.
      RESULTS: This paper proposes a method, called RAUR (Re-align the Unmapped Reads),
      to re-align the reads that can not be mapped by alignment tools. Firstly, it
      takes advantages of the base quality scores (reported by the sequencer) to figure
      out the most confident and informative segments of the unmapped reads by
      controlling the number of possible mismatches in the alignment. Then, combined
      with an alignment tool, RAUR re-align these segments of the reads. We run RAUR on
      both simulated data and real data with different read lengths. The results show
      that many reads which fail to be aligned by the most popular alignment tools (BWA
      and Bowtie2) can be correctly re-aligned by RAUR, with a similar Precision. Even
      compared with the BWA-MEM and the local mode of Bowtie2, which perform local
      alignment for long reads to improve the alignment rate, RAUR also shows
      advantages on the Alignment rate and Precision in some cases. Therefore, the
      trimming strategy used in RAUR is useful to improve the Alignment rate of
      alignment tools for the next-generation genome sequencing. AVAILABILITY: All
      source code are available at http://netlab.csu.edu.cn/bioinformatics/RAUR.html.

PMID- 25860435
TI  - Quantitative 1H NMR analysis of egg yolk, alcohol, and total sugar content in egg
      liqueurs.
AB  - Analyzing egg liqueurs for compliance with legal requirements means several
      different time-consuming preparations and analytical processes. In this paper, we
      describe the approach to use quantitative (1)H NMR spectroscopy as an accurate
      alternative technique. (1)H NMR analysis comprised two different rapid sample
      preparations for water-soluble or nonpolar ingredients. Fifteen egg liqueurs were
      analyzed for alcoholic strength and content of total sugar and egg yolk
      (estimated by cholesterol as a marker substance) with both classical methods and
      quantitative (1)H NMR spectroscopy. The results of both methods showed excellent
      correlations for alcoholic strength (R = 0.996, p < 0.001) and content of total
      sugar (R = 0.989, p < 0.001) and cholesterol (R = 0.995, p < 0.001). Besides, NMR
      spectra revealed further information: a signal of phosphatidylcholine at about
      delta = 3.20 ppm served as a second marker for the egg yolk content, and
      characteristic signals of lactose at delta = 4.46 ppm and butyric acid at delta =
      0.97 ppm indicated the use of milk products, which has to be declared for lactose
      intolerant consumers. 

PMID- 25860437
TI  - Editorial: genomics and criminal law.

PMID- 25860436
TI  - Clinical Muscle Testing Compared with Whole-Body Magnetic Resonance Imaging in
      Facio-scapulo-humeral Muscular Dystrophy.
AB  - OBJECTIVE: The objective of this study was to evaluate the clinical usefulness of
      whole-body magnetic resonance imaging (MRI) in facio-scapulo-humeral muscular
      dystrophy (FSHD). METHODS: In 20 patients with genetically proven FSHD1, we
      prospectively assessed muscular involvement and correlated the results of semi
      quantitative manual muscle testing and other parameters such as disease duration,
      creatine kinase (CK) levels and repeat length of the D4Z4 locus with whole-body
      MRI. RESULTS: Clinical muscle testing revealed the trapezius, pectoralis and
      infraspinatus as the most severely affected muscles in the shoulder, and the knee
      flexors and gluteus medius in the hip girdle. MRI revealed the trapezius and
      serratus anterior muscles in the shoulder, and the hamstrings and adductor
      muscles in the hip girdle, as the most severely affected muscle groups. Overall,
      degrees of fatty degeneration on MRI scans correlated significantly with clinical
      weakness. Moreover, we could detect clear affection of the trunk muscles.
      Corresponding to earlier reports, asymmetric involvement was frequent in both
      clinical examination and MRI scoring. Moreover, MRI revealed inhomogeneous muscle
      degeneration in a considerable proportion of both, muscles and patients. Both
      clinical and MRI scores significantly correlated to disease duration, but not to
      fragment size or CK levels. CONCLUSION: Fatty degeneration in whole-body MRI
      correlates well to clinical muscle testing of the extremities but gives more
      information on deeper or trunk muscles. It shows structural changes in muscular
      disorders and may become an excellent tool for assessment of muscle involvement
      and follow-up studies.

PMID- 25860438
TI  - The potential use of genetics to increase the effectiveness of treatment programs
      for criminal offenders.
AB  - During the past couple of decades, the amount of research examining the genetic
      underpinnings to antisocial behaviors, including crime, has exploded. Findings
      from this body of work have generated a great deal of information linking
      genetics to criminal involvement. As a partial result, there is now a
      considerable amount of interest in how these findings should be integrated into
      the criminal justice system. In the current paper, we outline the potential ways
      that genetic information can be used to increase the effectiveness of treatment
      programs designed to reduce recidivism among offenders. We conclude by drawing
      attention to how genetic information can be used by rehabilitation programs to
      increase program effectiveness, reduce offender recidivism rates, and enhance
      public safety. 

PMID- 25860439
TI  - The role of Na+/Ca2+ exchanger subtypes in neuronal ischemic injury.
AB  - The Na(+)/Ca(2+) exchanger (NCX) plays an important role in the maintenance of
      Na(+) and Ca(2+) homeostasis in most cells including neurons under physiological
      and pathological conditions. It exists in three subtypes (NCX1-3) with different
      tissue distributions but all of them are present in the brain. NCX transports
      Na(+) and Ca(2+) in either Ca(2+)-efflux (forward) or Ca(2+)-influx (reverse)
      mode, depending on membrane potential and transmembrane ion gradients. During
      neuronal ischemia, Na(+) and Ca(2+) ionic disturbances favor NCX to work in
      reverse mode, giving rise to increased intracellular Ca(2+) levels, while it may
      regain its forward mode activity on reperfusion. The exact significance of NCX in
      neuronal ischemic and reperfusion states remains unclear. The differential role
      of NCX subtypes in ischemic neuronal injury has been extensively investigated
      using various pharmacological tools as well as genetic models. This review
      discusses the mode of action of NCX in ischemic and reperfusion states, the
      differential roles played by NCX subtypes in these states as well as the role of
      NCX in pre- and postconditioning. NCX subtypes carry variable roles in ischemic
      injury. Furthermore, the mode of action of each subtype varies in ischemia and
      reperfusion states. Thus, therapeutic targeting of NCX in stroke should be based
      on appropriate timing of the administration of NCX subtype-specific strategies. 

PMID- 25860440
TI  - Aneurysmal subarachnoid hemorrhage--status quo and perspective.

PMID- 25860441
TI  - Biochemical analysis of the NAD+-dependent malate dehydrogenase, a substrate of
      several serine/threonine protein kinases of Mycobacterium tuberculosis.
AB  - PknD is one of the eleven eukaryotic-like serine/threonine protein kinases
      (STPKs) of Mycobacterium tuberculosis (Mtb). In vitro phosphorylation assays with
      the active recombinant PknD showed that the intracellular protein NAD+-dependent
      malate dehydrogenase (MDH) is a substrate of this kinase. MDH, an energy
      supplying enzyme, catalyzes the interconversion of malate and oxaloacetate and
      plays crucial roles in several metabolic pathways including the citric acid
      cycle. The phosphorylation site was identified on threonine residues and the
      phosphorylation inhibited the MDH activity. In vitro, the recombinant MDH could
      also be phosphorylated by at least five other STPKs, PknA, PknE, PknH, PknJ, and
      PknG. Immunoprecipitation analysis revealed that MDH was hyperphosphorylated in
      the bacteria at the beginning of the stationary and under oxygen-limited
      conditions by STPKs other than PknD. On the contrary, when PknD-deficient mutant
      mycobacteria were grown in a phosphate-depleted medium, MDH was not detectably
      phosphorylated. These results suggest that although the MDH is a substrate of
      several mycobacterial STPKs, the activity of these kinases can depend on the
      environment, as we identified PknD as a key element in the MDH phosphorylation
      assay under phosphate-poor conditions. 

PMID- 25860442
TI  - Bone marrow stromal antigen 2 (BST-2) DNA is demethylated in breast tumors and
      breast cancer cells.
AB  - BACKGROUND: Bone marrow stromal antigen 2 (BST-2) is a known anti-viral gene that
      has been recently identified to be overexpressed in many cancers, including
      breast cancer. BST-2 is critical for the invasiveness of breast cancer cells and
      the formation of metastasis in vivo. Although the regulation of BST-2 in immune
      cells is unraveling, it is unknown how BST-2 expression is regulated in breast
      cancer. We hypothesized that meta-analyses of BST-2 gene expression and BST-2 DNA
      methylation profiles would illuminate mechanisms regulating elevated BST-2
      expression in breast tumor tissues and cells. MATERIALS AND METHODS: We performed
      comprehensive meta-analyses of BST-2 gene expression and BST-2 DNA methylation in
      The Cancer Genome Atlas (TCGA) and various Gene Expression Omnibus (GEO)
      datasets. BST-2 expression levels and BST-2 DNA methylation status at specific
      CpG sites on the BST-2 gene were compared for various breast tumor molecular
      subtypes and breast cancer cell lines. RESULTS: We show that BST-2 gene
      expression is inversely associated with the methylation status at specific CpG
      sites in primary breast cancer specimens and breast cancer cell lines. BST-2
      demethylation is significantly more prevalent in primary tumors and cancer cells
      than in normal breast tissues or normal mammary epithelial cells. Demethylation
      of the BST-2 gene significantly correlates with its mRNA expression. These
      studies provide the initial evidence that significant differences exist in BST-2
      DNA methylation patterns between breast tumors and normal breast tissues, and
      that BST-2 expression patterns in tumors and cancer cells correlate with
      hypomethylated BST-2 DNA. CONCLUSION: Our study suggests that the DNA methylation
      pattern and expression of BST-2 may play a role in disease pathogenesis and could
      serve as a biomarker for the diagnosis of breast cancer.

PMID- 25860443
TI  - Genetically encoded fragment-based discovery of glycopeptide ligands for
      carbohydrate-binding proteins.
AB  - We describe an approach to accelerate the search for competitive inhibitors for
      carbohydrate-recognition domains (CRDs). Genetically encoded fragment-based
      discovery (GE-FBD) uses selection of phage-displayed glycopeptides to dock a
      glycan fragment at the CRD and guide selection of synergistic peptide motifs
      adjacent to the CRD. Starting from concanavalin A (ConA), a mannose (Man)-binding
      protein, as a bait, we narrowed a library of 10(8) glycopeptides to 86 leads that
      share a consensus motif, Man-WYD. Validation of synthetic leads yielded Man-WYDLF
      that exhibited 40-50-fold enhancement in affinity over methyl alpha-d
      mannopyranoside (MeMan). Lectin array suggested specificity: Man-WYD derivative
      bound only to 3 out of 17 proteins-ConA, LcH, and PSA-that bind to Man. An X-ray
      structure of ConA:Man-WYD proved that the trimannoside core and Man-WYD exhibit
      identical CRD docking, but their extra-CRD binding modes are significantly
      different. Still, they have comparable affinity and selectivity for various Man
      binding proteins. The intriguing observation provides new insight into functional
      mimicry of carbohydrates by peptide ligands. GE-FBD may provide an alternative to
      rapidly search for competitive inhibitors for lectins.

PMID- 25860445
TI  - Long-segment caval thrombus after removal of ECMO cannula.

PMID- 25860446
TI  - Ten strategies to increase survival of cardiac arrest patients.

PMID- 25860447
TI  - Breast cancer screening for women with Down syndrome: lessons learned.
AB  - This study examined mammogram reports of women with Down syndrome (DS) treated in
      the largest medical facility specifically serving adults with DS in the United
      States. Records of 684 women and results of 993 mammograms were reviewed,
      including 902 screening and 93 diagnostic mammograms. Only 2 (0.7%) women had a
      diagnosis of breast cancer. This study found a low rate of breast cancer among
      women with DS, a finding which is consistent with previous studies. The financial
      cost per finding was high, the benefit of the mammograms questionable, and the
      potential for harm greater. With less than 1% of the women with DS in this study
      developing breast cancer, further discussion is recommended to assess whether
      mammography is a beneficial, cost-effective part of health maintenance for women
      with DS. 

PMID- 25860448
TI  - Impact of adulthood stage and social-environmental context on body mass index and
      physical activity of individuals with intellectual disability.
AB  - Individuals with intellectual disability (ID) are at risk for obesity and
      physical inactivity. We analyzed a subset of 2009-2010 National Core Indicators
      (NCI) database to examine (1) the impact of three adulthood stages- younger (20
      39 years), middle (40-59 years), and older (60 years and older) on Body Mass
      Index (BMI) and physical activity (PA); and (2) the relationship between social
      environmental context (i.e., residence type, everyday choices, and community
      participation) and BMI and PA, with adjustment for individual characteristics of
      the adults with ID. Findings highlight the need to pay more attention to obesity
      by providing health education and emphasizing healthy choices. Results also
      suggest the importance of community participation as a way of promoting more
      physical activity. 

PMID- 25860449
TI  - Factors related to complications among adult patients with intellectual
      disabilities hospitalized at an academic medical center.
AB  - People with intellectual disabilities (ID) represent a small but important group
      of hospitalized patients who have higher rates of complications than do patients
      without ID hospitalized for the same reasons. Complications are potentially
      avoidable conditions, such as healthcare-acquired infections, healthcare-acquired
      skin breakdown, falls, and medication errors and reactions. Addressing factors
      related to complications can focus efforts to improve hospital care. The purpose
      of this exploratory study was to analyze data from reviews of academic medical
      center charts (N  =  70) about complications and to examine patient and
      hospitalization characteristics in relation to complications among adult patients
      (age >= 18 years) with ID hospitalized for nonpsychiatric reasons. Adults with ID
      tended to be twice as likely to have complications (chi2  =  2.893, df  =  1, p 
      =  .09) if they had a surgical procedure and were nearly four times as likely to
      have complications (chi2  =  6.836, df  =  1, p  =  .009) if they had multiple
      chronic health conditions (three of the following: history of cerebral palsy,
      autism spectrum symptoms, aggressive behavior, respiratory disorder, and
      admission through the emergency department). Findings suggest preliminary
      criteria for assessing risk for complications among hospitalized people with ID
      and the need for attention to their specific needs when hospitalized.

PMID- 25860450
TI  - Students with intellectual disability in higher education: adult service provider
      perspectives.
AB  - Postsecondary education (PSE) is increasingly becoming an option for students
      with intellectual disability (ID; Grigal & Hart, 2012 ). Postsecondary education
      offers the promise of pursuing a valued social role (that of college student),
      enhanced social networks, and, most significantly, increased employment options.
      To date, research and practice in the area of transition to PSE for students with
      ID has focused primarily upon the sending (public school systems) and receiving
      (colleges or universities) agencies ( Oertle & Bragg, 2014 ; Thoma et al., 2011
      ). Yet adults with ID often require ongoing supports through state and federally
      funded developmental disability waivers, and agency providers of waiver services
      have, for the most part, not been part of this vital conversation. This study
      represents an exploratory study of directors of developmental disability provider
      agencies in one midwestern state to assess their knowledge of PSE for individuals
      with ID. A total of 87 directors responded; quantitative results are presented
      and, based on these findings, we provide implications for the future. 

PMID- 25860451
TI  - The Portuguese version of personal outcomes scale: a psychometric validity and
      reliability study.
AB  - This article presents the results of a pilot study to evaluate the psychometric
      properties of the Escala Pessoal de Resultados (EPR), the Portuguese version of
      the Personal Outcomes Scale (POS), to assess quality of life (QOL) in people with
      intellectual disability (ID) in Portugal. We present the adaptation and
      validation processes of the EPR. Data were collected from 1,264 adults with
      intermittent and limited levels of support needs and respective proxies. Results
      of the research are discussed in requisites of the validity and reliability. The
      different coefficients illustrate that this scale may be a useful addition to the
      QOL assessment in Portuguese people with ID. 

PMID- 25860444
TI  - Prevalence and outcome of gastrointestinal bleeding and use of acid suppressants
      in acutely ill adult intensive care patients.
AB  - PURPOSE: To describe the prevalence of, risk factors for, and prognostic
      importance of gastrointestinal (GI) bleeding and use of acid suppressants in
      acutely ill adult intensive care patients. METHODS: We included adults without GI
      bleeding who were acutely admitted to the intensive care unit (ICU) during a 7
      day period. The primary outcome was clinically important GI bleeding in ICU, and
      the analyses included estimations of baseline risk factors and potential
      associations with 90-day mortality. RESULTS: A total of 1,034 patients in 97 ICUs
      in 11 countries were included. Clinically important GI bleeding occurred in 2.6 %
      (95 % confidence interval 1.6-3.6 %) of patients. The following variables at ICU
      admission were independently associated with clinically important GI bleeding:
      three or more co-existing diseases (odds ratio 8.9, 2.7-28.8), co-existing liver
      disease (7.6, 3.3-17.6), use of renal replacement therapy (6.9, 2.7-17.5), co
      existing coagulopathy (5.2, 2.3-11.8), acute coagulopathy (4.2, 1.7-10.2), use of
      acid suppressants (3.6, 1.3-10.2) and higher organ failure score (1.4, 1.2-1.5).
      In ICU, 73 % (71-76 %) of patients received acid suppressants; most received
      proton pump inhibitors. In patients with clinically important GI bleeding, crude
      and adjusted odds for mortality were 3.7 (1.7-8.0) and 1.7 (0.7-4.3),
      respectively. CONCLUSIONS: In ICU patients clinically important GI bleeding is
      rare, and acid suppressants are frequently used. Co-existing diseases, liver
      failure, coagulopathy and organ failures are the main risk factors for GI
      bleeding. Clinically important GI bleeding was not associated with increased
      adjusted 90-day mortality, which largely can be explained by severity of
      comorbidity, other organ failures and age.

PMID- 25860452
TI  - A comparative analysis of adult siblings' perceptions toward caregiving.
AB  - Siblings of individuals with intellectual and developmental disabilities (IDD)
      are likely to become caregivers for their brothers and sisters. The expectations
      of and experiences with caregiving, however, may be different. In this study,
      using focus groups, we compared the perspectives of siblings who were current
      caregivers (n  =  25) to siblings who anticipated being caregivers (n  =  17).
      Responses were compared and contrasted across four areas: caregiving
      responsibilities, rewards, challenges, and opinions toward being paid as a
      caregiver. Both caregiver groups were knowledgeable about and invested in their
      brothers and sisters. Also, they both reported that they enjoyed bonding with
      their brothers and sisters. Challenges, for current caregivers, related to
      understanding and navigating the service system. In contrast, anticipated
      caregivers were concerned about planning for the future. Mixed viewpoints were
      expressed about receiving pay for providing care although a greater number of
      current caregivers were receptive to it as a means to supporting their own
      families. 

PMID- 25860456
TI  - Synthesis of magnesium ZIF-8 from Mg(BH4)2.
AB  - Porous Mg(2-methyl imidazolate)2 (Mg-ZIF-8) was synthesised from Mg(BH4)2 as a
      precursor under an Ar atmosphere. It possesses an uncommon tetrahedral Mg(2+)-N
      coordination geometry that is stabilised by the formation of a framework, and it
      exhibits a Brunauer-Emmett-Teller surface area greater than 1800 m(2) g(-1). 

PMID- 25860455
TI  - Stem cell therapy for erectile dysfunction of cavernous nerve injury rats: a
      systematic review and meta-analysis.
AB  - INTRODUCTION: Stem cell treatment is a novel therapeutic strategy for erectile
      dysfunction (ED) patients with bilateral cavernous nerve injury (CNI). The
      relative animal studies provide important clues to design pre-clinical studies
      and clinical studies further in the future. PURPOSE: This study aims to evaluate
      the effects and influential factors of stem cell transplantation on ED rats with
      CNI. MATERIALS AND METHODS: We searched PubMed and EBSCO databases published
      before April 30, 2014 for pre-clinical studies to evaluate the efficacy of stem
      cell transplantation in the treatment of ED rats with CNI. A systematic review
      and a planned subgroup analysis were performed to identify whether or not some
      certain influential factors could bring significant effects on stem cell
      treatment. RESULTS: 12 studies with 319 rats were enrolled in this meta-analysis.
      Pooled analysis results confirmed the efficacy of stem cell transplantation.
      Subgroup analysis results showed that treatment effects were not related to CNI
      models, follow-up time, stem cell species, stem cell sources, markers and
      delivery approaches in the transplantation. Uncultured stem cells were poorly
      effective compared with cultured stem cells. Periprostatic implantation (PPI)
      with acellular scaffolds could promote cavernous nerve regeneration, but was less
      effective for smooth muscle cell recovery. Stem cells modified by NGF or BDNF
      combined with udenafil/bFGF seemed to be more effective than those modified by
      BDNF alone. CONCLUSION: This meta-analysis shows that stem cell therapy can be
      performed to recover erectile function. Future studies should focus on nerve
      restoration and vascular cell recovery. The synergistic actions of multiple
      growth factors following stem cell transplantation should also be considered as
      beneficial strategies to obtain preferable effects.

PMID- 25860457
TI  - New predictors of malignant ventricular arrhythmias in Chagas disease: searching
      for the holy grail.

PMID- 25860458
TI  - Risk factors associated with the transmission of Brazilian spotted fever in the
      Piracicaba river basin, State of Sao Paulo, Brazil.
AB  - INTRODUCTION: Brazilian spotted fever (BSF) is a disease transmitted by ticks for
      which the etiological agent is Rickettsia rickettsii. The present essay evaluates
      the risk factors associated with the transmission of cases of BSF in the time
      period between 2003 and 2013 in the Piracicaba river basin, state of Sao Paulo.
      METHODS: This essay presents a retrospective study to identify the factors
      associated with the transmission of cases of BSF among all suspected cases
      identified by the System for Epidemiological Surveillance of Sao Paulo (CVE).
      After the description of temporal distribution (onset of symptoms) and the
      environmental and demographic variations of the confirmed and discarded cases, a
      multiple logistic regression model was applied. RESULTS: We searched 569 probable
      locations of infection (PLI) with 210 (37%) confirmed cases of BSF and 359 (63%)
      discarded cases. The associated variables for the confirmation of BSF in the
      multiple logistic model using a confidence interval (CI) of 95% were age (OR =
      1.025 CI: 1.015-1.035), the presence of Amblyomma sculptum in the environment (OR
      = 1.629 CI: 1.097-2.439), the collection of ticks from horses (OR = 1.939 CI:
      0.999-3.764), the presence of capybaras (OR = 1.467 CI: 1.009-2.138), an urban
      environment (OR = 1.515 CI: 1.036-2.231), and the existence of a dirty pasture
      (OR = 1.759 CI: 1.028-3.003). CONCLUSIONS: The factors associated with the
      confirmation of BSF cases included an urban environment, age, presence of the A.
      sculptum vector, the collection of ticks from horses, the presence of a capybara
      population, and a dirty pasture environment.

PMID- 25860459
TI  - Natural transovarial transmission of dengue virus 4 in Aedes aegypti from Cuiaba,
      State of Mato Grosso, Brazil.
AB  - INTRODUCTION: Dengue is the most prevalent arboviral disease in tropical areas.
      In Mato Grosso, outbreaks are reported every year, but studies on dengue in this
      state are scarce. METHODS: Natural transovarial infection of Aedes aegypti by a
      flavivirus was investigated in the Jardim Industriario neighborhood of Cuiaba,
      Mato Grosso. Eggs were collected with ovitraps during the dry, intermediate, and
      rainy seasons of 2012. After the eggs hatched and the larvae developed to
      adulthood, mosquitoes (n = 758) were identified and allocated to pools of 1-10
      specimens according to the collection location, sex, and climatic period. After
      RNA extraction, multiplex semi-nested RT-PCR was performed to detect the four
      dengue virus (DENV) serotypes, yellow fever virus, West Nile virus and Saint
      Louis encephalitis virus. RESULTS: DENV-4 was the only flavivirus detected, and
      it was found in 8/50 pools (16.0%). Three of the positive pools contained
      females, and five contained males. Their nucleotide sequences presented 96-100%
      similarity with DENV-4 genotype II strains from Manaus, Amazonas. The minimum
      infection rate was 10.5 per 1000 specimens, and the maximum likelihood estimator
      of the infection rate was 11.6 (95% confidence interval: 4.8; 23.3). CONCLUSIONS:
      This study provides the first evidence of natural transovarial infection by DENV
      4 in Ae. Aegypti in Mato Grosso, suggesting that this type of infection might
      serve as a mechanism of virus maintenance during interepidemic periods in Cuiaba,
      a city where dengue epidemics are reported every year. These results emphasize
      the need for efficient vector population control measures to prevent arbovirus
      outbreaks in the state.

PMID- 25860460
TI  - Studies on Phlebotominae (Diptera: Psychodidae) in the campus FIOCRUZ mata
      Atlantica, Jacarepagua, in the City of Rio de Janeiro, Brazil.
AB  - INTRODUCTION: The presence of American cutaneous leishmaniasis (ACL) in the
      communities of the Campus FIOCRUZ Mata Atlantica (CFMA) in the City of Rio de
      Janeiro initiated the investigation of the Phlebotominae fauna in the Atlantic
      Forest to determine the occurrence of putative ACL vectors associated with the
      enzootic cycle. METHODS: For 24 consecutive months, sand flies were captured
      inside the forest and in the border area near the communities. RESULTS: The
      following sand fly species were identified: Brumptomyia brumpti, Brumptomyia
      cunhai, Brumptomyia nitzulescui, Lutzomyia edwardsi, Lutzomyia pelloni, and
      Lutzomyia quinquefer. Other identified sand fly vectors, such as Lutzomyia
      intermedia (the predominant species), Lutzomyia migonei, Lutzomyia whitmani,
      Lutzomyia fischeri, and Lutzomyia hirsuta hirsuta, are associated with ACL
      transmission, and the vector for American visceral leishmaniases (AVL), Lutzomyia
      longipalpis, was also found. CONCLUSIONS: All sand fly vectors were found in both
      studied environments except for Lutzomyia whitmani, which was only identified in
      the forest. This study represents the first identification of Lutzomyia
      longipalpis in the CFMA, and the epidemiological implications are discussed.

PMID- 25860461
TI  - The influence of the area of the Serra da Mesa Hydroelectric Plant, State of
      Goias, on the frequency and diversity of anophelines (Diptera: Culicidae): a
      study on the effect of a reservoir.
AB  - INTRODUCTION: Bioecological aspects of anophelines (Diptera: Culicidae) near
      areas under the direct influence of the hydroelectric plant reservoir of Serra da
      Mesa in Goias, Brazil, were analyzed. METHODS: Samples were collected at the
      surrounding dam area during the phases before and after reservoir impoundment.
      The influence of climatic and environmental factors on the occurrence of
      Anopheles darlingi, Anopheles albitarsis, Anopheles triannulatus, Anopheles
      oswaldoi and Anopheles evansae was assessed using Pearson's correlations with
      indicators for richness and diversity as well as the index of species abundance
      (ISA) and the standardized index of species abundance (SISA). RESULTS: The
      highest anopheline density occurred during the phase after filling the tank;
      however, no direct correlation with the climatic factors was observed during this
      stage. The reservoir formation determined the incidence of the anopheline
      species. An. darlingi was the predominant species (SISA = 1.00). CONCLUSIONS: The
      significant difference (p < 0.05) observed between the species incidence during
      the different reservoir phases demonstrates the environmental effect of the
      reservoir on anophelines.

PMID- 25860462
TI  - Toxicological profile of deltamethrin in Triatoma brasiliensis (Hemiptera:
      Reduviidae) in State of Ceara, Northeastern Brazil.
AB  - INTRODUCTION: Triatoma brasiliensis is the species of greatest epidemiological
      relevance in the semi-arid region of Brazil. This species is predominantly found
      in domestic environments, and it has the ability to build large colonies with
      high levels of natural infection via Trypanosoma cruzi. Thus, T. brasiliensis is
      one of the most efficient transmitters of Chagas disease (CD) to humans. Despite
      household spraying with residual insecticides, many areas report persistent
      reinfestations for reasons that remain poorly understood. Therefore, this study
      sought to characterize the toxicological profile of deltamethrin in T.
      brasiliensis from areas with persistent reinfestation in State of Ceara, Brazil.
      METHODS: The susceptibility reference lineage (SRL) was derived from Umari.
      Serial dilutions of deltamethrin were prepared and applied to the dorsal abdomen
      of first instar nymphs. The control group received only pure acetone. Mortality
      was evaluated after 72h. Qualitative tests assessed mortality in response to a
      diagnostic dose of 1xLD99 (0.851 nanograms of active ingredient per treated
      nymph) of the SRL. RESULTS: The susceptibility profile characterization of the T.
      brasiliensis populations revealed 50% resistance ratios (RR50) that ranged from
      0.32 to 1.21. The percentage of mortality in response to the diagnostic dose was
      100%. CONCLUSIONS: We demonstrated that T. brasiliensis was highly susceptible to
      deltamethrin. The control difficulties found might be related to the
      recolonization of the triatomines originating from neighboring environments and
      the possible operational failures related to the process of spraying that enabled
      specimens less susceptible to deltamethrin to survive.

PMID- 25860463
TI  - Impact of the antipneumococcal conjugate vaccine on the occurrence of infectious
      respiratory diseases and hospitalization rates in children.
AB  - INTRODUCTION: In 2010, to reduce the occurrence of serious pneumococcal disease,
      the Ministry of Health in Brazil incorporated the 10-valent pneumococcal vaccine
      in the immunization schedule of children younger than two years of age. The
      objective of this study was to evaluate the impact of vaccination on the
      incidence of infectious respiratory diseases in infants before and after the
      introduction of the 10-valent pneumococcal vaccine. METHODS: This cross-sectional
      study involved primary care and hospital networks from a city in Minas Gerais
      State, Brazil, between 2009 and 2012. RESULTS: A 40% reduction in the prevalence
      of community-acquired pneumonia (CAP) was observed after introducing the
      pneumococcal conjugate vaccine. Male children were 28% more likely to develop the
      disease. The prevalence ratio ([PR] = 1.96, 95% CI: 1.52 to 2.53, p < 0.05)
      suggested that not being vaccinated was associated with the occurrence of
      pneumonia. The prevalence of CAP was 70% lower (PR 0.30, 95% CI: 0.24 to 0.37,
      p<0.05) in children vaccinated as recommended compared to children with delayed
      vaccination, suggesting that the updated vaccine schedule improves protection.
      CONCLUSIONS: Immunization with the 10-valent pneumococcal vaccine appeared to
      reduce the number of pneumonia cases in children during the study period.
      Prospective studies are needed to confirm the efficacy of the vaccine against the
      occurrence of pneumococcal pneumonia.

PMID- 25860464
TI  - Seroprevalence and seroincidence of Leptospira infection in dogs during a one
      year period in an endemic urban area in Southern Brazil.
AB  - INTRODUCTION: Leptospirosis is a zoonosis that affects both humans and animals.
      Dogs may serve as sentinels and indicators of environmental contamination as well
      as potential carriers for Leptospira. This study aimed to evaluate the
      seroprevalence and seroincidence of leptospirosis infection in dogs in an urban
      low-income community in southern Brazil where human leptospirosis is endemic.
      METHODS: A prospective cohort study was designed that consisted of sampling at
      recruitment and four consecutive trimestral follow-up sampling trials. All
      households in the area were visited, and those that owned dogs were invited to
      participate in the study. The seroprevalence (MAT titers >=100) of Leptospira
      infection in dogs was calculated for each visit, the seroincidence
      (seroconversion or four-fold increase in serogroup-specific MAT titer) density
      rate was calculated for each follow-up, and a global seroincidence density rate
      was calculated for the overall period. RESULTS: A total of 378 dogs and 902.7 dog
      trimesters were recruited and followed, respectively. The seroprevalence of
      infection ranged from 9.3% (95% CI; 6.7 - 12.6) to 19% (14.1 - 25.2), the
      seroincidence density rate of infection ranged from 6% (3.3 - 10.6) to 15.3%
      (10.8 - 21.2), and the global seroincidence density rate of infection was 11%
      (9.1 - 13.2) per dog-trimester. Canicola and Icterohaemorraghiae were the most
      frequent incident serogroups observed in all follow-ups. CONCLUSIONS: Follow-ups
      with mean trimester intervals were incapable of detecting any increase in
      seroprevalence due to seroincident cases of canine leptospirosis, suggesting that
      antibody titers may fall within three months. Further studies on incident
      infections, disease burden or risk factors for incident Leptospira cases should
      take into account the detectable lifespan of the antibody.

PMID- 25860466
TI  - Leishmania, Babesia and Ehrlichia in urban pet dogs: co-infection or cross
      reaction in serological methods?
AB  - INTRODUCTION: The present study was designed to assess the occurrence of co
      infection or cross-reaction in the serological techniques used for detecting the
      anti-Leishmania spp., -Babesia canis vogeli and -Ehrlichia canis antibodies in
      urban dogs from an area endemic to these parasites. METHODS: The serum samples
      from dogs were tested for the Babesia canis vogeli strain Belo Horizonte antigen
      and Ehrlichia canis strain Sao Paulo by immunofluorescence antibody test (IFAT)
      and by anti-Leishmania immunoglobulin G (IgG) antibody detection to assess
      Leishmania infection. We used the following four commercial kits for canine
      visceral leishmaniasis: ELISA, IFAT, Dual Path Platform (DPP) (Bio
      Manguinhos(r)/FIOCRUZ/MS) and a rK39 RDT (Kalazar Detect Canine Rapid Test;
      Inbios). RESULTS: Of 96 serum samples submitted to serological assays, 4 (4.2%)
      were positive for Leishmania as determined by ELISA; 12 (12.5%), by IFAT; 14
      (14.6%) by rK39 RDT; and 20 (20.8%), by DPP. Antibodies against Ehrlichia and
      Babesia were detected in 23/96 (23.9%) and 30/96 (31.2%) samples, respectively.
      No significant association was identified between the results of tests for
      detecting Babesia or Ehrlichia and those for detecting Leishmania (p-value>0.05).
      CONCLUSIONS: In the present study, we demonstrated co-infection with Ehrlichia or
      Babesia and Leishmania in dogs from Minas Gerais (Brazil); we also found that the
      serological tests that were used did not cross-react.

PMID- 25860465
TI  - Toxoplasma gondii infection: seroprevalence and associated risk factors among
      primary schoolchildren in Lagos City, Southern Nigeria.
AB  - INTRODUCTION: Toxoplasma gondii infection has been described as the most
      widespread zoonotic infection of humans and other animals. Information concerning
      T. gondii infection among schoolchildren is unavailable in Lagos City, Nigeria.
      METHODS: This cross-sectional study investigated the seroprevalence and risk
      factors associated with T. gondii infection among primary schoolchildren (PSC)
      from a community located in the center of Lagos, southern Nigeria, from November
      2013 to March 2014. A total of 382 PSC were screened for the presence of sera
      anti-T. gondii antibodies using a latex agglutination test (TOXO Test-MT, Tokyo,
      Japan). A cutoff titer of >= 1:32 was considered positive, while titers >=
      1:1,024 indicated high responders. Questionnaires were also used to obtain data
      on possible risk factors from parents/guardians. RESULTS: The overall
      seroprevalence was 24% (91/382), and 83.5% (76/91) of seropositive PSC were
      classified as high responders. Among the risk factors tested, including contact
      with cats and soil, consumption of raw meat and vegetables, and drinking unboiled
      water, none showed statistical significance after multivariate adjustment. No
      associations were observed among age, gender, body mass index (BMI), and parents'
      occupation/educational level. CONCLUSIONS: The findings in this study show
      evidence of active infection, and hence, there is need for urgent preventive
      measures in this city. Further investigation is required to clarify the
      transmission routes. Policy makers also need to initiate prevention and control
      programs to protect pregnant women and immunocompromised patients in particular
      because they are more severely affected by T. gondii infection.

PMID- 25860467
TI  - Pulmonary tuberculosis in Sao Luis, State of Maranhao, Brazil: space and space
      time risk clusters for death (2008-2012).
AB  - INTRODUCTION: The objective was to identify space and space-time risk clusters
      for the occurrence of deaths in a priority city for the control of tuberculosis
      (TB) in the Brazilian Northeast. METHODS: Ecological research was undertaken in
      the City of Sao Luis/Maranhao. Cases were considered that resulted in deaths in
      the population living in the urban region of the city with pulmonary TB as the
      basic cause, between 2008 and 2012. To detect space and space-time clusters of
      deaths due to pulmonary TB in the census sectors, the spatial analysis scan
      technique was used. RESULTS: In total, 221 deaths by TB occurred, 193 of which
      were due to pulmonary TB. Approximately 95% of the cases (n=183) were geocoded.
      Two significant spatial clusters were identified, the first of which showed a
      mortality rate of 5.8 deaths per 100,000 inhabitants per year and a high relative
      risk of 3.87. The second spatial cluster showed a mortality rate of 0.4 deaths
      per 100,000 inhabitants per year and a low relative risk of 0.10. A significant
      cluster was observed in the space-time analysis between 11/01/2008 and
      04/30/2011, with a mortality rate of 8.10 deaths per 100,000 inhabitants per year
      and a high relative risk (3.0). CONCLUSIONS: The knowledge of priority sites for
      the occurrence of deaths can support public management to reduce inequities in
      the access to health services and permit an optimization of the resources and
      teams in the control of pulmonary TB, providing support for specific strategies
      focused on the most vulnerable populations.

PMID- 25860468
TI  - Evaluation of the predictive indices for candidemia in an adult intensive care
      unit.
AB  - INTRODUCTION: To evaluate predictive indices for candidemia in an adult intensive
      care unit (ICU) and to propose a new index. METHODS: A prospective cohort study
      was conducted between January 2011 and December 2012. This study was performed in
      an ICU in a tertiary care hospital at a public university and included 114
      patients staying in the adult ICU for at least 48 hours. The association of
      patient variables with candidemia was analyzed. RESULTS: There were 18 (15.8%)
      proven cases of candidemia and 96 (84.2%) cases without candidemia. Univariate
      analysis revealed the following risk factors: parenteral nutrition, severe
      sepsis, surgical procedure, dialysis, pancreatitis, acute renal failure, and an
      APACHE II score higher than 20. For the Candida score index, the odds ratio was
      8.50 (95% CI, 2.57 to 28.09); the sensitivity, specificity, positive predictive
      value, and negative predictive value were 0.78, 0.71, 0.33, and 0.94,
      respectively. With respect to the clinical predictor index, the odds ratio was
      9.45 (95%CI, 2.06 to 43.39); the sensitivity, specificity, positive predictive
      value, and negative predictive value were 0.89, 0.54, 0.27, and 0.96,
      respectively. The proposed candidemia index cutoff was 8.5; the sensitivity,
      specificity, positive predictive value, and negative predictive value were 0.77,
      0.70, 0.33, and 0.94, respectively. CONCLUSIONS: The Candida score and clinical
      predictor index excluded candidemia satisfactorily. The effectiveness of the
      candidemia index was comparable to that of the Candida score.

PMID- 25860469
TI  - Oral and systemic manifestations in HIV-1 patients.
AB  - INTRODUCTION: This study aimed to estimate the prevalence of the most frequent
      oral and systemic manifestations in human immunodeficiency virus-1 (HIV-1)
      positive patients. METHODS: The study was conducted on 300 HIV-1 patients
      attending the Reference Unit Specialized in Special Infectious Parasitic Diseases
      in Belem, Para, Brazil. RESULTS: The most prevalent oral conditions were caries
      (32.6%), candidiasis (32%), and periodontal disease (17%). Among the systemic
      manifestations, hepatitis (29.2%), gastritis (16%), arterial hypertension
      (14.7%), and tuberculosis (12%) were the most commonly observed. CONCLUSIONS: We
      here reported on the most prevalent oral and systemic conditions in HIV-1
      positive patients. The healthcare professional's knowledge of the various
      manifestations among these patients is fundamental to ensure prompt and accurate
      diagnosis and treatment, and for improving the quality of life of these patients.

PMID- 25860470
TI  - Twenty-eight years of Aedes albopictus in Brazil: a rationale to maintain active
      entomological and epidemiological surveillance.
AB  - INTRODUCTION: Aedes albopictus was first detected in Brazil in 1986. This
      mosquito species presents a major threat to public health because Brazilian
      populations have shown substantial vector competence for arboviruses such as
      dengue and chikungunya. METHODS: We updated the records of Ae. albopictus in
      several States of Brazil, focusing on areas in which its presence had been
      reported after 2002. RESULTS: Twenty-eight years after its arrival in Brazil, Ae.
      albopictus has been detected in 24 of 27 States. CONCLUSIONS: The rapid spread of
      this species and its high vector competence demonstrate the danger of Ae.
      albopictus in Brazil.

PMID- 25860471
TI  - Frequency of the toxic shock syndrome toxin-1 gene in methicillin-susceptible and
      -resistant Staphylococcus aureus isolates from teaching hospitals in Shiraz,
      Iran.
AB  - INTRODUCTION: Staphylococcus aureus produces a range of virulence factors such as
      toxic shock syndrome toxin-1. METHODS: In this cross-sectional study of 345
      clinical S. aureus isolates, the presence of the tst gene was assessed by
      polymerase chain reaction (PCR). RESULTS: The study revealed 53/345 (15.4%)
      isolates were positive for the tst gene. The tst gene was present in 18.1% of
      methicillin-susceptible S. aureus (MSSA) isolates and 11.6% of methicillin
      resistant S. aureus (MRSA) isolates (p = 0.136). CONCLUSIONS: These results
      reveal the remarkable risk of S. aureus infections in hospitals, regardless of
      methicillin-resistance status.

PMID- 25860472
TI  - Detection of bla KPC-2 in Proteus mirabilis in Brazil.
AB  - INTRODUCTION: Infections caused by Klebsiella pneumoniae carbapenemase (KPC)
      producing isolates pose a major worldwide public health problem today. METHODS: A
      carbapenem-resistant Proteus mirabilis clinical isolate was investigated for
      plasmid profiles and the occurrence of beta-lactamase genes. RESULTS: The isolate
      exhibited resistance to ertapenem and imipenem and was susceptible to meropenem,
      polymyxin, and tigecycline. Five plasmids were identified in this isolate. DNA
      sequencing analysis revealed the presence of bla KPC-2 and bla TEM-1 genes. An
      additional PCR using plasmid DNA confirmed that bla KPC-2 was present in one of
      these plasmids. CONCLUSIONS: We report the detection of bla KPC-2 in P. mirabilis
      in Brazil for the first time. This finding highlights the continuous transfer of
      bla KPC between bacterial genera, which presents a serious challenge to the
      prevention of infection by multidrug-resistant bacteria.

PMID- 25860473
TI  - Characteristics of pregnant and lactating women with leprosy.
AB  - INTRODUCTION: The clinical characteristics of women who conceive during leprosy
      and the association between leprosy and pregnancy are not well known. METHODS:
      This cross-sectional study included 49 pregnant or lactating women diagnosed with
      leprosy in 2011. RESULTS: The patients had a clinical dimorphous form of leprosy
      (44.9%), no physical incapacity at diagnosis (87.5%), and no complications in
      either the patient or infant (33.4%). In 36.3% of cases, leprosy symptoms were
      presented in the last trimester of pregnancy, and in 31.9% of patients were in
      the first trimester of lactation. CONCLUSIONS: The association between leprosy
      and pregnancy should be routinely investigated, particularly in endemic areas.

PMID- 25860474
TI  - The epidemiology of envenomation via snakebite in the State of Piaui,
      Northeastern Brazil.
AB  - INTRODUCTION: This communication describes a retrospective study of the
      epidemiology of snakebite cases that were recorded from 2007 to 2012 in the State
      of Piaui, northeastern Brazil. METHODS: Data were collected from the Injury
      Notification Information System database of the State of Piaui's Health
      Department. RESULTS: A total of 1,528 cases were identified. The cases occurred
      most frequently in rural areas between January and July. Victims were
      predominantly male farmers, and were typically 30-39 years old. Most victims were
      bitten on the foot, and received medical assistance within 1-3h after being
      bitten. CONCLUSIONS: The epidemiological profile of snakebites in the State of
      Piaui is similar to that in all of Brazil.

PMID- 25860475
TI  - Using mobile technology to conduct epidemiological investigations.
AB  - INTRODUCTION: The aim of this study was to report the experience of an
      epidemiological field survey for which data were collected and analyzed using
      tablets. METHODS: The devices used Epi Info 7 (Android version), which has been
      modeled a database with variables of the traditional form. RESULTS: Twenty-one
      households were randomly selected in the study area; 75 residents were registered
      and completed household interviews with socioeconomic and environmental risk
      variables. CONCLUSIONS: This new technology is a valuable tool for collecting and
      analyzing data from the field, with advantageous benefits to epidemiological
      surveys.

PMID- 25860476
TI  - Diagnosing lymphoma in a setting with a high burden of infection: a pediatric
      case of Epstein-Barr virus-associated aggressive B-cell lymphoma with t(8;14)
      (q23;q32) and extensive necrosis mimicking tuberculosis.
AB  - The association of lymphoma with necrotic granuloma can pose diagnostic
      challenges and delay treatment, especially in settings with a high burden of
      infection. In these settings, the timely use of cytogenetic and molecular methods
      is most relevant. Here, we report a case of B-cell lymphoma with t (8;14) in a 5
      year-old male child. The lymphoma was associated with necrotic granuloma and was
      initially misdiagnosed as tuberculosis. Polymerase chain reaction was used to
      detect clonal lymphoproliferation and to rule out Mycobacterium tuberculosis
      infection. Tumor cells harbored Epstein-Barr virus and expressed CD20, CD10,
      BCL6, and Ki67 (30%), leading to the diagnosis of B-cell lymphoma with features
      intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma. 

PMID- 25860477
TI  - Primary inoculation tuberculosis: a report of a rare entity.
AB  - Primary inoculation tuberculosis is an exogenous infection resulting from direct
      inoculation of bacteria into individuals with no acquired immunity to the
      organism. We report a 63-year-old male patient who was diagnosed with primary
      inoculation tuberculosis on the basis of clinical appearance and
      histopathological examination. The findings from this case emphasize the
      importance of clinical and histopathological findings in this rarely seen form of
      skin tuberculosis if the organism cannot be shown to grow in culture. 

PMID- 25860478
TI  - Tumoral presentation of invasive cerebral aspergillosis.

PMID- 25860479
TI  - Correction: Polygonum cuspidatum and its active components inhibit replication of
      the influenza virus through toll-like receptor 9-induced interferon beta
      expression.

PMID- 25860480
TI  - Expression and function of S100A8/A9 (calprotectin) in human typhoid fever and
      the murine Salmonella model.
AB  - BACKGROUND: Typhoid fever, caused by the Gram-negative bacterium Salmonella
      enterica serovar Typhi, is a major cause of community-acquired bacteremia and
      death worldwide. S100A8 (MRP8) and S100A9 (MRP14) form bioactive antimicrobial
      heterodimers (calprotectin) that can activate Toll-like receptor 4, promoting
      lethal, endotoxin-induced shock and multi-organ failure. We aimed to characterize
      the expression and function of S100A8/A9 in patients with typhoid fever and in a
      murine invasive Salmonella model. METHODS AND PRINCIPAL FINDINGS: S100A8/A9
      protein levels were determined in acute phase plasma or feces from 28 Bangladeshi
      patients, and convalescent phase plasma from 60 Indonesian patients with blood
      culture or PCR-confirmed typhoid fever, and compared to 98 healthy control
      subjects. To functionally characterize the role of S100A8/A9, we challenged
      wildtype (WT) and S100A9-/- mice with S. Typhimurium and determined bacterial
      loads and inflammation 2- and 5- days post infection. We further assessed the
      antimicrobial function of recombinant S100A8/A9 on S. Typhimurium and S. Typhi
      replication in vitro. Typhoid fever patients demonstrated a marked increase of
      S100A8/A9 in acute phase plasma and feces and this increases correlated with
      duration of fever prior to admission. S100A8/A9 directly inhibited the growth of
      S. Typhimurium and S. Typhi in vitro in a dose and time dependent fashion. WT
      mice inoculated with S. Typhimurium showed increased levels of S100A8/A9 in both
      the liver and the systemic compartment but S100A9-/- mice were indistinguishable
      from WT mice with respect to bacterial growth, survival, and inflammatory
      responses, as determined by cytokine release, histopathology and organ injury.
      CONCLUSION: S100A8/A9 is markedly elevated in human typhoid, correlates with
      duration of fever prior to admission and directly inhibits the growth of S.
      Typhimurium and S. Typhi in vitro. Despite elevated levels in the murine invasive
      Salmonella model, S100A8/A9 does not contribute to an effective host response
      against S. Typhimurium in mice.

PMID- 25860482
TI  - Correction: EpCAM knockdown alters microRNA expression in retinoblastoma-
      functional implication of EpCAM regulated miRNA in tumor progression.

PMID- 25860481
TI  - Investigation of salivary function and oral microbiota of radiation caries-free
      people with nasopharyngeal carcinoma.
AB  - Radiation caries have been reported to be correlated with radiotherapy-induced
      destruction of salivary function and changes in oral microbiota. There have been
      no published reports detailing patients who have remained radiation caries-free
      following radiotherapy for nasopharyngeal carcinoma. The aim of this study was to
      investigate the relationship between salivary function, oral microbiota and the
      absence of radiation caries. Twelve radiation caries-free patients and nine
      patients exhibiting radiation caries following irradiated nasopharyngeal
      carcinoma were selected. V40, the dose at which the volume of the contralateral
      parotid gland receives more than 40 Gy, was recorded. Stimulated saliva flow
      rate, pH values and buffering capacity were examined to assess salivary function.
      Stimulated saliva was used for molecular profiling by Denaturing Gradient Gel
      Electrophoresis. Mutans streptococci and Lactobacilli in saliva were also
      cultivated. There were no significant differences in V40 between radiation caries
      free individuals and those with radiation caries. Compared with normal values,
      the radiation caries-free group had significantly decreased simulated saliva flow
      rate, while there were no significant differences in the saliva pH value and
      buffering capacity. Similar results were observed in the radiation caries group.
      There was no statistical difference in microbial diversity, composition and log
      CFU counts in cultivation from the radiation caries-free group and the radiation
      caries group. Eleven genera were detected in these two groups, among which
      Streptococcus spp. and Neisseria spp. had the highest distribution. Our results
      suggest that changes in salivary function and in salivary microbiota do not
      explain the absence of radiation caries in radiation caries-free individuals. 

PMID- 25860483
TI  - Slug-dependent upregulation of L1CAM is responsible for the increased invasion
      potential of pancreatic cancer cells following long-term 5-FU treatment.
AB  - BACKGROUND: Pancreatic adenocarcinoma is a lethal disease with 5-year survival of
      less than 5%. 5-fluorouracil (5-FU) is a principal first-line therapy, but
      treatment only extends survival modestly and is seldom curative. Drug resistance
      and disease recurrence is typical and there is a pressing need to overcome this.
      To investigate acquired 5-FU resistance in pancreatic adenocarcinoma, we
      established chemoresistant monoclonal cell lines from the Panc 03.27 cell line by
      long-term exposure to increasing doses of 5-FU. RESULTS: 5-FU-resistant cell
      lines exhibited increased expression of markers associated with multidrug
      resistance explaining their reduced sensitivity to 5-FU. In addition, 5-FU
      resistant cell lines showed alterations typical for an epithelial-to-mesenchymal
      transition (EMT), including upregulation of mesenchymal markers and increased
      invasiveness. Microarray analysis revealed the L1CAM pathway as one of the most
      upregulated pathways in the chemoresistant clones, and a significant upregulation
      of L1CAM was seen on the RNA and protein level. In pancreatic cancer, expression
      of L1CAM is associated with a chemoresistant and migratory phenotype. Using
      esiRNA targeting L1CAM, or by blocking the extracellular part of L1CAM with
      antibodies, we show that the increased invasiveness observed in the
      chemoresistant cells functionally depends on L1CAM. Using esiRNA targeting beta
      catenin and/or Slug, we demonstrate that in the chemoresistant cell lines, L1CAM
      expression depends on Slug rather than beta-catenin. CONCLUSION: Our findings
      establish Slug-induced L1CAM expression as a mediator of a chemoresistant and
      migratory phenotype in pancreatic adenocarcinoma cells.

PMID- 25860484
TI  - Transcription factors and microRNA-co-regulated genes in gastric cancer invasion
      in ex vivo.
AB  - Aberrant miRNA expression abnormally modulates gene expression in cells and can
      contribute to tumorigenesis in humans. This study identified functionally
      relevant differentially expressed genes using the transcription factors and miRNA
      co-regulated network analysis for gastric cancer. The TF-miRNA co-regulatory
      network was constructed based on data obtained from cDNA microarray and miRNA
      expression profiling of gastric cancer tissues. The network along with their co
      regulated genes was analyzed using Database for Annotation, Visualization and
      Integrated Discovery (DAVID) and Transcriptional Regulatory Element Database
      (TRED). We found eighteen (17 up-regulated and 1 down-regulated) differentially
      expressed genes that were co-regulated by transcription factors and miRNAs. KEGG
      pathway analysis revealed that these genes were part of the extracellular matrix
      receptor interaction and focal adhesion signaling pathways. In addition, qRT- PCR
      and Western blot data showed an increase in COL1A1 and decrease in NCAM1 mRNA and
      protein levels in gastric cancer tissues. Thus, these data provided the first
      evidence to illustrate that altered gene network was associated with gastric
      cancer invasion. Further study with a large sample size and more functional
      experiments is needed to confirm these data and contribute to diagnostic and
      treatment strategies for gastric cancer. 

PMID- 25860485
TI  - The prognostic impact of multiparameter flow cytometry immunophenotyping and
      cytogenetic aberrancies in patients with multiple myeloma.
AB  - OBJECTIVES: The aim of this study was to evaluate the prognostic impact of
      immunophenotyping in patients with multiple myeloma (MM), as well as other
      markers of disease, such as serum hyaluronan and cytogenetic aberrancies.
      METHODS: We have prospectively analyzed the prognostic impact of antigenic
      markers, assessed by multiparametric flow cytometry (MFC), in a series of newly
      diagnosed MM patients (n = 79). RESULTS AND DISCUSSION: Our results show that the
      expression of CD44, CD45, and CD28 and the absence of CD117 were associated with
      a significantly shorter progression free-survival (PFS). Clinical characteristics
      were collected; Cytogenetic aberrancies were assessed in 40 patients.
      Multivariate survival analyses identified that the CD117(-), CD28(+), CD45(+),
      and the percentage of bone marrow plasma cells by MFC are survival predictor,
      along with the International Staging System stage. Interestingly, the CD117(-)
      patients were associated with chromosomal aberrancies, including del (17p),
      +1q21, and IgH translocations. CONCLUSION: The incorporation of multiparameter
      flow cytometry immunophenotyping into the routine diagnostic evaluation of MM
      patients can help to identify patients at a high risk of progression.

PMID- 25860486
TI  - [Introduction to the reference issue 20150].

PMID- 25860487
TI  - [Epidemiology of chronic rhinosinusitis, selected risk factors, comorbidities and
      economic burden].
AB  - Chronic rhinosinusitis (CRS) is a relevant and prevalent medical condition in
      Germany, Europe and the world. If analysed in detail, the prevalence of CRS shows
      regional and temporary variety. In this review, currently available data
      regarding the prevalence of CRS is therefore sorted by country and/or region,
      time point of data collection and the CRS-definition employed. Risk factors like
      smoking and gastro-oesophageal reflux are discussed regarding their influence on
      CRS prevalence. Moreover, co-morbidities of CRS, like asthma, conditions of the
      cardiovascular system and depression are listed and their influence on CRS is
      discussed. Furthermore, data on CRS prevalence in special cohorts, like
      immunocompromised patients, are presented. To estimate the economic burden of
      CRS, current data e.g. from Germany and the USA are included in this review. 

PMID- 25860488
TI  - [Hemostatic management of patients undergoing ear-nose-throat-surgery].
AB  - Perioperative hemostatic management is increasingly important in Otolaryngology.
      This review summarizes the key elements of perioperative risk stratification,
      thromboprophylaxis, and therapies for bridging of antithrombotic treatment. It
      gives a practical advise based on the current literature with an emphasis for
      patients undergoing ear-nose-throat surgery. 

PMID- 25860489
TI  - [Comprehensive review on rhino-neurosurgery].
AB  - In the past 2 decades, an innovative and active field of surgical collaboration
      has been evolved and established combining the expertise of Neurosurgery and
      Rhinosurgery in treatment of different lesions affecting the anterior skull base
      together with the adjacent intranasal and intradural areas. Important
      prerequesites for this development were improvements of technical devices,
      definitions of transnasal surgical corridors and approvements in endonasal
      reconstruction e. g. by use of pedicled nasal mucosal flaps. Interdisciplinary
      surgical teams have been established constituting specialized centers of "rhino
      neurosurgery". With growing experience of these groups, it could be shown that
      oncological results and perioperative complications were comparable to
      traditional surgery while at the same time, patient's morbidity could be
      reduced.The present review encompasses the recent literature focussing on the
      development, technical details, results and complications of "rhino
      neurosurgery". 

PMID- 25860490
TI  - [Trauma of the midface].
AB  - Fractures of the midface pose a serious medical problem as for their complexity,
      frequency and their socio-economic impact. Interdisciplinary approaches and up-to
      date diagnostic and surgical techniques provide favorable results in the majority
      of cases though. Traffic accidents are the leading cause and male adults in their
      thirties are affected most often. Treatment algorithms for nasal bone fractures,
      maxillary and zygoma fractures are widely agreed upon whereas trauma to the
      frontal sinus and the orbital apex are matter of current debate. Advances in
      endoscopic surgery and limitations of evidence based gain of knowledge are
      matters that are focused on in the corresponding chapter. As for the fractures of
      the frontal sinus a strong tendency towards minimized approaches can be seen.
      Obliteration and cranialisation seem to decrease in numbers.Some critical remarks
      in terms of high dose methylprednisolone therapy for traumatic optic nerve injury
      seem to be appropriate.Intraoperative cone beam radiographs and preshaped
      titanium mesh implants for orbital reconstruction are new techniques and
      essential aspects in midface traumatology. Fractures of the anterior skull base
      with cerebrospinal fluid leaks show very promising results in endonasal
      endoscopic repair.

PMID- 25860491
TI  - [Principles of hygiene in ENT endoscopy].
AB  - This article gives a report on principles of reprocessing of rigid and flexible
      endoscopes used in ENT units including structural and spatial requirements based
      on the general and also ENT-specific risks of infection associated with
      diagnostic and therapeutic endoscopy. The underlying legal principles as well as
      recommendations from scientific societies will be exemplified in order to give
      the otorhinolaryngologist a practical guidance.Preliminary results of a nation
      wide survey on infection control standards based on data of 29 ENT practices in
      Germany reveal actual deficits of varying degree concerning infection control
      management including reprocessing of endoscopes. The presented review aims to
      give support to the establishment of a structured infection control management
      program including the evaluation of results by means of a prospective
      surveillance. 

PMID- 25860492
TI  - [Optimized imaging of the midface and orbits].
AB  - A variety of imaging techniques are available for imaging the midface and orbits.
      This review article describes the different imaging techniques based on the
      recent literature and discusses their impact on clinical routine imaging. Imaging
      protocols are presented for different diseases and the different imaging
      modalities. 

PMID- 25860493
TI  - [Orphan disease of the nose and paranasal sinuses].
AB  - Rare rhinological diseases are a diagnostic challenge. From the primary
      manifestation until the final diagnosis it may take several months or even up to
      years in which the disease progress is uncontrolled and the disease
      insufficiently treated. This results in (irreversible) damage and possibly life
      threatening situations. The unexpected course of a (misdiagnosed) disease should
      lead to further diagnostic considerations and steps to detect the orphan disease
      at a stage as early as possible. In the present work granulomatous diseases of
      the nose and sinuses caused by mycobacteria, treponemes, klebsiella, fungi and
      protozoa as well as vasculitis, sarcoidosis, rosacea, the cocaine-induced midline
      destruction, the nasal extranodal NK/T-cell lymphoma and cholesterol granuloma
      are discussed. Furthermore diseases with disorders of mucociliary clearance as
      the primary ciliary dyskinesia and cystic fibrosis are presented taking into
      account the current literature. 

PMID- 25860494
TI  - [Minimally invasive surgery of the anterior skull base: transorbital approaches].
AB  - Minimally invasive approaches are becoming increasingly popular to access the
      anterior skull base. With interdisciplanary cooperation, endonasal endoscopic in
      particular approaches have seen an impressive expansion of indications over the
      past decades. The more recently described transorbital approaches represent
      minimally invasive alternatives with a differing spectrum of access corridors.
      The purpose of the present paper is to discuss transorbital approaches to the
      anterior skull base in the light of the current literature.The transorbital
      approaches allow excellent exposure of difficult to reach areas like the the
      anterior and posterior wall of the frontal sinus; working angles may be more
      favorable and the paranasal sinus system can be preserved while exposing the base
      of skull. Because of their minimal morbidity and the cosmetically excellent
      results, the transorbital approaches represent an important addition to
      established endonasal endoscopic and open approaches to the anterior skull base.
      Their execution requires an interdisciplinary team approach. 

PMID- 25860495
TI  - [Position paper of the German Society of Oto-Rhino-Laryngology, Head and Neck
      Surgery and the German Society of Phoniatrics and Pediatric Audiology - current
      state of clinical and endoscopic diagnostics, evaluation, and therapy of
      swallowing disorders in children and adults].
AB  - Position Paper of the German Society of Oto-Rhino-Laryngology, Head and Neck
      Surgery and the German Society of Phoniatrics and Pediatric Audiology - Current
      State of Clinical and Endoscopic Diagnostics, Evaluation, and Therapy of
      Swallowing Disorders in Children and AdultsSwallowing disorders are frequent. The
      main concern is mortality due to aspiration induced pneumonia and malnutrition.
      On the other hand quality of life is severely affected. The demographic trend
      indicates an increase of dysphagia in the future. Neurodegenerative diseases,
      tumors of the digestive tract and sequelae of tumor treatment in the head and
      neck region are the main pathologic entities.Predominantly ENT physicians and
      phoniatrists, are asked for diagnostics and therapy who will coordinate the
      interdisciplinary treatment according to the endoscopic findings.A differentiated
      approach in history, diagnostics, and symptom oriented treatment is necessary for
      the mostly complex disorders. The integration of non-medical personnel such as
      logopeds (speech language pathologists), physiotherapists, and occupational
      therapists in planning and executing an effective therapy expands and completes
      the patient-oriented care. Conservative treatment by these therapists is an
      important pillar in the treatment. Parts of the specific diagnostics can be taken
      over by them in close cooperation.In particular an interdisciplinary cooperation
      with the staff from intensive care medicine is indispensable.The diagnostic
      procedures of specific endoscopy as described in this position paper are part of
      the primary and fundamental tasks of ENT specialists and phoniatrists.Endoscopy
      is a medical service that is basically not delegable. Consequently substitution
      of the physician is precluded. 

PMID- 25860496
TI  - [Pathophysiology of chronic rhinosinusitis, pharmaceutical therapy options].
AB  - Research in immunology has brought great progress in knowledge of inflammatory
      processes in the last 2 decades, which also has an impact on the upper airways.
      Our understanding of the pathophysiology of chronic rhinosinusitis developed from
      a rather mechanistic point of view with a focus on narrow clefts and mucociliary
      clearance to the appreciation of a complex network of immunological pathways
      forming the basis of disease. We today differentiate various forms of
      inflammation, we start to understand complex immune-regulatory networks and the
      reasons for their failure, and have already developed innovative approaches for
      therapy for the most severely ill subjects. Due to this new knowledge in
      inflammation and remodeling processes within mucosal tissue, specifically on the
      key driving factors, new diagnostic tools and therapeutic approaches for chronic
      rhinosinusitis have developed; the differentiation of endotypes based on
      pathophysiological principles will be crucial for the use of innovative
      therapies, mostly humanized monoclonal antibodies. Several hundred of those
      antibodies are currently developed for various indications and will impact our
      speciality as well as pneumology to a great extent. 

PMID- 25860497
TI  - [Comprehensive review on endonasal endoscopic sinus surgery].
AB  - Endonasal endoscopic sinus surgery is the standard procedure for surgery of most
      paranasal sinus diseases.Appropriate frame conditions provided, the respective
      procedures are safe and successful.These prerequisites encompass appropriate
      technical equipment, anatomical oriented surgical technique, proper patient
      selection, and individually adapted extent of surgery.The range of endonasal
      sinus operations has dramatically increased during the last 20 years and reaches
      from partial uncinectomy to pansinusoperation with extended surgery of the
      frontal (Draf type III), maxillary (grade 3-4, medial maxillectomy, prelacrimal
      approach) and sphenoid sinus.In addition there are operations outside and beyond
      the paranasal sinuses. The development of surgical technique is still constantly
      evolving.This article gives a comprehensive review on the most recent state of
      the art in endoscopic sinus surgery according to the literature with the
      following aspects: principles and fundamentals, surgical techniques, indications,
      outcome, postoperative care, nasal packing and stents, technical equipment. 

PMID- 25860498
TI  - Anti-proliferative, apoptotic and signal transduction effects of hesperidin in
      non-small cell lung cancer cells.
AB  - PURPOSE: Hesperidin, a glycoside flavonoid, is thought to act as an anti-cancer
      agent, since it has been found to exhibit both pro-apoptotic and anti
      proliferative effects in several cancer cell types. The mechanisms underlying
      hesperidin-induced growth arrest and apoptosis are, however, not well understood.
      Here, we aimed to investigate the anti-proliferative and apoptotic effects of
      hesperidin on non-small cell lung cancer (NSCLC) cells and to investigate the
      mechanisms involved. METHODS: The anti-proliferative and apoptotic effects of
      hesperidin on two NSCLC-derived cell lines, A549 and NCI-H358, were determined
      using a WST-1 colorimetric assay, a LDH cytotoxicity assay, a Cell Death
      Detection assay, an AnnexinV-FITC assay, a caspase-3 assay and a JC-1 assay,
      respectively, all in a time- and dose-dependent manner. As a control, non
      cancerous MRC-5 lung fibroblasts were included. Changes in whole genome gene
      expression profiles were assessed using an Illumina Human HT-12v4 beadchip
      microarray platform, and subsequent data analyses were performed using an
      Illumina Genome Studio and Ingenuity Pathway Analyser (IPA). RESULTS: We found
      that after hesperidin treatment, A549 and NCI-H358 cells exhibited decreasing
      cell proliferation and increasing caspase-3 and other apoptosis-related
      activities, in conjunction with decreasing mitochondrial membrane potential
      activities, in a dose- and time-dependent manner. Through a GO analysis, by which
      changes in gene expression profiles were compared, we found that the FGF and NF
      kappaB signal transduction pathways were most significantly affected in the
      hesperidin treated NCI-H358 and A549 NSCLC cells. CONCLUSIONS: Our results
      indicate that hesperidin elicits an in vitro growth inhibitory effect on NSCLC
      cells by modulating immune response-related pathways that affect apoptosis. When
      confirmed in vivo, hesperidin may serve as a novel anti-proliferative agent for
      non-small cell lung cancer.

PMID- 25860499
TI  - Biomechanical and neural changes evaluation induced by prolonged use of non
      stable footwear: a systematic review.
AB  - The aim of this review is to collect and discuss the current best evidence
      published in literature about the effect of the Masai Barefoot Technology(MBT)
      shoes on gait and muscle activation and try to draw conclusions on the possible
      benefits. We searched Medline, CINAHL, Embase and the Cochrane Central Registry
      of Controlled Trials. The reference lists of the previously selected articles
      were then examined by hand. Only studies comparing biomechanical and clinical
      outcomes were selected. Review, anatomical studies, letter to editor and
      instructional course were excluded. Finally, all the resulting articles were
      reviewed and discussed by all the authors to further confirm their suitability
      for this review: in the end, 22 articles were included. A total of 532 patients
      presenting a mean age of 34.3 years were studied. All patients evaluated were
      healthy or amateur sports except in two studies where only obese subjects and
      knee osteoarthritis patients were involved. Seven studies evaluated only male
      subjects, whereas four studies evaluated only female. Twelve of twenty-two
      studies performed electromyographic analyses. Weight was reported in 19 studies,
      whereas body mass index were reported only in a five studies. All studies
      reported kinematic analysis of shoe effects and compared the relationship between
      muscle recruitment and electromyographic activity. Unstable footwears were shown
      to immediately alter the stability in gait during daily-life activities. The
      center of body pressure is moved posteriorly with a consequent posterior
      displacement of the upper part of body in order to regain an appropriate body
      balance, and these postural changes are associated with an overall increase in
      the activity of lumbar erector spine muscles, as well as certain lower limb
      muscles. Current literature provides enough cues to conclude for a beneficial
      role of MBT shoes in the postural and proprioceptive recovery, but from the same
      literature cannot be drown clear and appropriate guidance to determine more in
      detail their indication for specific pathological conditions or for particular
      phases of the musculoskeletal recovery process. 

PMID- 25860500
TI  - AIIMS test: a simple test to look for presence of palmaris longus.
AB  - PURPOSE: Palmaris longus has an invaluable role in reconstructive surgeries of
      hand and is the most common source of tendon grafts in tendon transfer surgeries.
      Various clinical tests are available to check for the presence of the tendon but
      are often difficult to use due to their complex nature. We suggest a rather
      simple test, which we have found very useful in our practice. METHODS: In this
      cross-sectional study, we compared our proposed test with the most commonly used
      Standard test (Schaeffer's test) to know about its sensitivity in a cohort of
      randomly selected 200 patients. RESULTS: We found our test to be more sensitive
      than the Standard test. The average time duration from instructions to
      elicitation of the test was also found less. No individual asked to repeat the
      instructions for the proposed test. CONCLUSIONS: Our proposed test to evaluate
      the presence of palmaris longus tendon is very simple and easy-to-understand
      manoeuvre with good sensitivity. It would be extremely useful in the preoperative
      planning in most of the reconstructive surgeries, should the palmaris longus
      tendon be harvested.

PMID- 25860501
TI  - CD4(+)T-lymphocyte subsets in nonobese children with obstructive sleep apnea
      syndrome.
AB  - BACKGROUND: To characterize the distribution of both tonsillar and circulating
      CD4(+)T-lymphocyte subsets, and to explore their clinical relevance in nonobese
      children with obstructive sleep apnea syndrome (OSAS). METHODS: A total of 53
      children who underwent tonsillectomy for either OSAS (n = 25) or primary snoring
      (PS, n = 28) were prospectively enrolled. Nineteen healthy children without any
      symptoms were recruited as controls. We quantified the frequencies of CD4(+)T
      lymphocyte subpopulations using flow cytometry, serum-related cytokines using
      enzyme-linked immunosorbent assay, and key transcription factors using
      quantitative polymerase chain reaction (qPCR). RESULTS: Tonsillar distributions
      of CD4(+)T-lymphocyte subsets were comparable in the OSAS and PS subjects. The
      peripheral Th17/Treg ratio was positively correlated to severity as measured by
      apnea/hypopnea index (AHI), serum C-reactive protein and hypoxia-inducible factor
      1alpha mRNA in the OSAS children (P < 0.05). And AHI was independently associated
      with the peripheral Th17/Treg ratio (P < 0.05). Furthermore, the response to
      surgery was associated with a significant reversal of the Th17/Treg imbalance and
      a concomitant relief of the proinflammatory profile in the OSAS subjects.
      CONCLUSION: Pediatric OSAS was associated with an altered Th17:Treg balance
      toward Th17 predominance. The changes in lymphocytic phenotypes that correlated
      with recurrent intermittent hypoxia in sleep apnea may contribute to the variance
      in systemic inflammation and downstream morbidities of pediatric OSAS.

PMID- 25860503
TI  - Covalent molecular probes for class A G protein-coupled receptors: advances and
      applications.
AB  - Covalent modification of G protein-coupled receptors (GPCRs) by employing
      specific molecular probes has for decades provided a successful strategy to
      facilitate the elucidation of the structure and function of this
      pharmacologically important class of membrane proteins. The ligands typically
      comprise a pharmacophore that generates affinity for a given GPCR and contain a
      reactive functionality that may form a covalent bond with a suitably positioned
      amino acid residue. Covalent ligands have been successfully applied to circumvent
      poor affinity of compounds when stable labeling of receptor populations was
      required, and they have been used in the isolation, purification, and
      pharmacological characterization of specific subtypes of GPCRs. Recently,
      structural studies have demonstrated that covalent molecular probes are effective
      at stabilizing GPCRs to obtain X-ray crystal structures, thus providing valuable
      insights for the development of novel therapeutics. Herein, we review covalently
      binding molecular probes for class A GPCRs with a focus on ligands comprising
      cross-linking groups that do not require photoactivation and further highlight
      their significant and diverse applications. 

PMID- 25860502
TI  - In Ovo injection of betaine affects hepatic cholesterol metabolism through
      epigenetic gene regulation in newly hatched chicks.
AB  - Betaine is reported to regulate hepatic cholesterol metabolism in mammals.
      Chicken eggs contain considerable amount of betaine, yet it remains unknown
      whether and how betaine in the egg affects hepatic cholesterol metabolism in
      chicks. In this study, eggs were injected with betaine at 2.5 mg/egg and the
      hepatic cholesterol metabolism was investigated in newly hatched chicks. Betaine
      did not affect body weight or liver weight, but significantly increased the serum
      concentration (P < 0.05) and the hepatic content (P < 0.01) of cholesterol.
      Accordingly, the cholesterol biosynthetic enzyme HMGCR was up-regulated (P < 0.05
      for both mRNA and protein), while CYP7A1 which converts cholesterol to bile acids
      was down-regulated (P < 0.05 for mRNA and P = 0.07 for protein). Moreover,
      hepatic protein content of the sterol-regulatory element binding protein 1 which
      regulates cholesterol and lipid biosynthesis, and the mRNA abundance of ATP
      binding cassette sub-family A member 1 (ABCA1) which mediates cholesterol counter
      transport were significantly (P < 0.05) increased in betaine-treated chicks.
      Meanwhile, hepatic protein contents of DNA methyltransferases 1 and
      adenosylhomocysteinase-like 1 were increased (P < 0.05), which was associated
      with global genomic DNA hypermethylation (P < 0.05) and diminished gene
      repression mark histone H3 lysine 27 trimethylation (P < 0.05). Furthermore, CpG
      methylation level on gene promoters was found to be increased (P < 0.05) for
      CYP7A1 yet decreased (P < 0.05) for ABCA1. These results indicate that in ovo
      betaine injection regulates hepatic cholesterol metabolism in chicks through
      epigenetic mechanisms including DNA and histone methylations. 

PMID- 25860504
TI  - Enantioselective total syntheses of (+)-hostmanin A, (-)-linderol A, (+)
      methyllinderatin and structural reassignment of adunctin E.
AB  - A one-step protocol has been developed for the enantioselective synthesis of
      hexahydrodibenzofuran derivatives using a modified Friedel-Crafts reaction. The
      developed method was applied to the synthesis of a series of natural products
      including (+)-hostmanin A, (+)-methyllinderatin, and (-)-linderol A. The
      synthetic and spectroscopic data investigations led to the structural
      reassignment of natural product adunctin E, which was further confirmed by single
      crystal X-ray analysis. 

PMID- 25860505
TI  - When should we change our clinical practice based on the results of a clinical
      study? The hierarchy of evidence.

PMID- 25860506
TI  - Syndromic lipomatosis of the head and neck: a review of the literature.
AB  - INTRODUCTION: Patients with syndromic causes of lipomatosis of the head and neck,
      although rare, often present late in the course of the disease in a myriad of
      ways, including concomitant airway obstruction, severe functional limitations,
      and/or significant cosmetic defects. The goal of this report was to review the
      literature and present a concise overview of the major syndromes causing
      lipomatosis of the head and neck. METHODS: A literature search was performed to
      gather information on syndromic lipomatosis of the head and neck region. PubMed
      was searched for the following conditions: Familial multiple lipomatosis (FML),
      multiple symmetrical lipomatosis (MSL), congenital infiltrating lipomatosis of
      the face (CIL-F), and Nasopalpebral lipoma-coloboma syndrome (NLCS). Data
      gathered included results of surgical cases of the head and neck region. RESULTS:
      A total of 48 reports comprising 172 cases of syndromic lipomatosis of the head
      and neck region were deemed eligible for review. Eighty-five percent of patients
      were male with an average age of 35 years. Seventy-four percent of cases appeared
      in the neck region, whereas 23 % presented in the face and scalp. 89 % of cases
      were treated with surgical excision, with 11 % of cases treated with liposuction.
      The most common complications were hematoma and seroma in MSL, recurrence in FML,
      neuropraxia in CIL-F, and mild telecanthus in NLCS. CONCLUSIONS: Syndromic causes
      of lipomatosis are generally benign in nature but difficult to control long term.
      Because these conditions include frequent recurrence and subsequent difficulty in
      clearing the disease, the authors advocate early and aggressive surgical excision
      of syndromic lipomatosis. NO LEVEL ASSIGNED: This journal requires that authors
      assign a level of evidence to each submission to which Evidence-Based Medicine
      rankings are applicable. This excludes Review Articles, Book Reviews, and
      manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and
      Experimental Studies. For a full description of these Evidence-Based Medicine
      ratings, please refer to the Table of Contents or the online Instructions to
      Authors www.springer.com/00266 .

PMID- 25860509
TI  - Adaptive and robust radiation therapy in the presence of drift.
AB  - Combining adaptive and robust optimization in radiation therapy has the potential
      to mitigate the negative effects of both intrafraction and interfraction
      uncertainty over a fractionated treatment course. A previously developed adaptive
      and robust radiation therapy (ARRT) method for lung cancer was demonstrated to be
      effective when the sequence of breathing patterns was well-behaved. In this
      paper, we examine the applicability of the ARRT method to less well-behaved
      breathing patterns. We develop a novel method to generate sequences of
      probability mass functions that represent different types of drift in the
      underlying breathing pattern. Computational results derived from applying the
      ARRT method to these sequences demonstrate that the ARRT method is effective for
      a much broader class of breathing patterns than previously demonstrated. 

PMID- 25860508
TI  - The relationship between temperament and autistic traits in a non-clinical
      students sample.
AB  - Since temperament affects the development of social behaviours and interpersonal
      relations, the possible links between autistic traits and temperament are of
      particular interest. The purpose of the study was to explore the relationships
      between autistic traits and temperamental characteristics in the framework of the
      Regulative Temperament Theory by Strelau, and the Emotionality, Activity and
      Sociability theory by Buss and Plomin, with particular emphasis on gender
      differences. The Autism Spectrum Quotient (AQ), Formal Characteristics of
      Behaviour--Temperament Inventory and Temperament Survey for Adults were
      administered. The participants were 593 university students, including 364
      females and 229 males. Results showed positive correlations between autistic
      traits and Emotional Reactivity, Perseveration, Distress, Fear and Anger, and
      negative correlations with Activity, Briskness, Endurance and Sociability. The
      results of multiple regression analyses involving the Autism Spectrum Quotient
      score as a dependent measure were different for females and males. Results of
      exploratory PCA analysis showed that AQ score, Sociability and Activity loaded
      one factor (with AQ loading being opposite to two others). High AQ scorers
      demonstrated higher Emotional Reactivity, Perseveration, Distress and Anger, and
      lower Briskness, Endurance, Activity and Sociability as compared to norms for the
      general population. In this study we showed that temperament measures were able
      to identify items that correlated in parts with autistic traits, while other
      items were obverse. The relationships between temperament and autistic traits
      differ slightly between genders. We assume that with regard to the broader autism
      phenotype, temperaments might be helpful in characterizing healthy control
      samples.

PMID- 25860507
TI  - Expression levels of MHC class I molecules are inversely correlated with
      promiscuity of peptide binding.
AB  - Highly polymorphic major histocompatibility complex (MHC) molecules are at the
      heart of adaptive immune responses, playing crucial roles in many kinds of
      disease and in vaccination. We report that breadth of peptide presentation and
      level of cell surface expression of class I molecules are inversely correlated in
      both chickens and humans. This relationship correlates with protective responses
      against infectious pathogens including Marek's disease virus leading to lethal
      tumours in chickens and human immunodeficiency virus infection progressing to
      AIDS in humans. We propose that differences in peptide binding repertoire define
      two groups of MHC class I molecules strategically evolved as generalists and
      specialists for different modes of pathogen resistance. We suggest that
      differences in cell surface expression level ensure the development of optimal
      peripheral T cell responses. The inverse relationship of peptide repertoire and
      expression is evidently a fundamental property of MHC molecules, with
      ramifications extending beyond immunology and medicine to evolutionary biology
      and conservation. 

PMID- 25860511
TI  - para-C-H Borylation of Benzene Derivatives by a Bulky Iridium Catalyst.
AB  - A highly para-selective aromatic C-H borylation has been accomplished. By a new
      iridium catalyst bearing a bulky diphosphine ligand, Xyl-MeO-BIPHEP, the C-H
      borylation of monosubstituted benzenes can be affected with para-selectivity up
      to 91%. This catalytic system is quite different from the usual iridium catalysts
      that cannot distinguish meta- and para-C-H bonds of monosubstituted benzene
      derivatives, resulting in the preferred formation of meta-products. The para
      selectivity increases with increasing bulkiness of the substituent on the arene,
      indicating that the regioselectivity of the present reaction is primarily
      controlled by steric repulsion between substrate and catalyst. Caramiphen, an
      anticholinergic drug used in the treatment of Parkinson's disease, was converted
      into five derivatives via our para-selective borylation. The present
      [Ir(cod)OH]2/Xyl-MeO-BIPHEP catalyst represents a unique, sterically controlled,
      para-selective, aromatic C-H borylation system that should find use in
      streamlined, predictable chemical synthesis and in the rapid discovery and
      optimization of pharmaceuticals and materials. 

PMID- 25860510
TI  - The role of HOXB9 and miR-196a in head and neck squamous cell carcinoma.
AB  - BACKGROUND: Previous studies have demonstrated that a number of HOX genes, a
      family of transcription factors with key roles in early development, are up
      regulated in head and neck squamous cell carcinoma (HNSCC) and other cancers. The
      loci of several Homeobox (HOX) genes also contain microRNAs (miRs), including miR
      196a. METHODS: Global miR expression and expression of all 39 HOX genes in normal
      oral keratinocytes (NOKs), oral pre-malignant (OPM) and HNSCC cells was assessed
      by expression microarray and qPCR and in tissues by immunohistochemistry (IHC)
      and qPCR of laser microdissected (LCM) tissues. Expression of miR196a and HOXB9
      was reduced using anti-miR-196a and siRNA, respectively. Expression microarray
      profiles of anti-miR196a and pre-miR196a transfected cells were compared to
      parental cells in order to identify novel targets of miR-196a. Putative miR196a
      targets were validated by qPCR and were confirmed as binding to the 3'UTR of
      miR196a by a dual luciferase reporter assay combined with mutational analysis of
      the miR-196a binding site. RESULTS: miR-196a and HOXB9 are highly expressed in
      HNSCC compared to NOKs, a pattern also seen in HNSCC tissues by HOXB9 IHC and
      qPCR of miR-196a in LCM tissue. Knock-down of miR-196a expression decreased HNSCC
      cell migration, invasion and adhesion to fibronectin, but had no effect on
      proliferation. Furthermore, knock-down of HOXB9 expression decreased migration,
      invasion and proliferation but did not alter adhesion. We identified a novel
      primary mRNA transcript containing HOXB9 and miR196a-1 as predicted from in
      silico analysis. Expression array analysis identified a number of miR196a
      targets, including MAMDC2 and HOXC8. We confirmed that MAMDC2 is a novel miR-196a
      target using a dual luciferase reporter assay with the effect abolished on
      mutation of the binding site. CONCLUSIONS: These results show that miR-196a and
      HOXB9 are overexpressed, perhaps co-ordinately, as HNSCC develops and exert a pro
      tumourigenic phenotype in HNSCC and OPM cells.

PMID- 25860512
TI  - Janus kinase-1 and Janus kinase-2 inhibitors for treating myelofibrosis.
AB  - BACKGROUND: Myelofibrosis is a bone marrow disorder characterized by excessive
      production of reticulin and collagen fiber deposition caused by hematological and
      non-hematological disorders. The prognosis of myelofibrosis is poor and treatment
      is mainly palliative. Janus kinase inhibitors are a novel strategy to treat
      people with myelofibrosis. OBJECTIVES: To determine the clinical benefits and
      harms of Janus kinase-1 and Janus kinase-2 inhibitors for treating myelofibrosis
      secondary to hematological or non-hematological conditions. SEARCH METHODS: We
      searched the Cochrane Central Register of Controlled Trials (CENTRAL, the
      Cochrane Library 2014, Issue 11), Ovid MEDLINE (from 1946 to 13 November 2014),
      EMBASE (from 1980 to 12 January 2013), and LILACS (from 1982 to 20 November
      2014). We searched WHO International Clinical Trials Registry Platform and The
      metaRegister of Controlled Trials. We also searched for conference proceedings of
      the American Society of Hematology (from 2009 to October 2013), European
      Hematology Association (from 2009 to October 2013), American Society of Clinical
      Oncology (from 2009 to October 2013), and European Society of Medical Oncology
      (from 2009 to October 2013). We included searches in FDA, European Medicines
      Agency, and Epistemonikos. We handsearched the references of all identified
      included trials, and relevant review articles. We did not apply any language
      restrictions. Two review authors independently screened search results. SELECTION
      CRITERIA: We included randomized clinical trials comparing Janus kinase-1 and
      Janus kinase-2 inhibitors with placebo or other treatments. Both previously
      treated and treatment naive patients were included. DATA COLLECTION AND ANALYSIS:
      We used the hazard ratio (HR) and 95% confidence interval (95% CI) for overall
      survival, progression-free survival and leukemia-free survival, risk ratio (RR)
      and 95% CI for reduction in spleen size and adverse events binary data, and
      standardized mean differences (SMD) and 95% CI for continuous data (health
      related quality of life). Two review authors independently extracted data and
      assessed the risk of bias of included trials. Primary outcomes were overall
      survival, progression-free survival and adverse events. MAIN RESULTS: We included
      two trials involving 528 participants, comparing ruxolitinib with placebo or best
      available therapy (BAT). As the two included trials had different comparators we
      did not pool the data. The confidence in the results estimates of these trials
      was low due to the bias in their design, and their limited sample sizes that
      resulted in imprecise results.There is low quality evidence for the effect of
      ruxolitinib on survival when compared with placebo at 51 weeks of follow-up (HR
      0.51, 95% CI 0.27 to 0.98) and compared with BAT at 48 weeks of follow-up (HR
      0.70, 95% CI 0.20 to 2.47). Similarly there was very low quality evidence for the
      effect of ruxolitinib on progression free survival compared with BAT (HR 0.81,
      95% CI 0.47 to 1.39).There is low quality evidence for the effect of ruxolitinib
      in terms of quality of life. Compared with placebo, the drug achieved a greater
      proportion of patients with a significant reduction of symptom scores (RR 8.82,
      95% CI 4.40 to 17.69), and treated patients with ruxolitinib obtained greater
      MFSAF scores at the end of follow-up (MD -87.90, 95% CI -139.58 to -36.22). An
      additional trial showed significant differences in EORTC QLQ-C30 scores when
      compared ruxolitinib with best available therapy (MD 7.60, 95% CI 0.35 to
      14.85).The effect of ruxolitinib on reduction in the spleen size of participants
      compared with placebo or BAT was uncertain (versus placebo: RR 64.58, 95% CI 9.08
      to 459.56, low quality evidence; versus BAT: RR 41.78, 95% CI 2.61 to 669.75, low
      quality evidence).There is low quality evidence for the effect of the drug
      compared with placebo on anemia (RR 2.35, 95% CI 1.62 to 3.41), neutropenia (RR
      3.57, 95% CI 1.02 to 12.55) and thrombocytopenia (RR 9.74, 95% CI 2.32 to 40.96).
      Ruxolitinib did not result in differences versus BAT in the risk of anemia (RR
      1.35, 95% CI 0.91 to 1.99, low quality evidence) or thrombocytopenia (RR 1.20;
      95% CI 0.44 to 3.28, low quality evidence). The risk of non-hematologic grade 3
      or 4 adverse events (including fatigue, arthralgia, nausea, diarrhea, extremity
      pain and pyrexia) was similar when ruxolitinib was compared with placebo or BAT.
      The rate of neutropenia comparing ruxolitinib with standard medical treatment was
      not reported by the trial. AUTHORS' CONCLUSIONS: Currently, there is insufficient
      evidence to allow any conclusions regarding the efficacy and safety of
      ruxolitinib for treating myelofibrosis. The findings of this Cochrane review
      should be interpreted with caution as they are based on trials sponsored by
      industry, and include a small number of patients. Unless powered randomized
      clinical trials provide strong evidence of a treatment effect, and the trade-off
      between potential benefits and harms is established, clinicians should be
      cautious when administering ruxolitinib for treating patients with myelofibrosis.

PMID- 25860514
TI  - Regioselective formation of multiple disulfide bonds with the aid of
      postsynthetic S-tritylation.
AB  - Disulfide bond formation performed in solution with the tert-butylthio (StBu)
      group was accomplished using a free peptide having only the sulfhydryl groups of
      Cys protected with the aid of postsynthetic S-tritylation. This facilitated
      removal of the StBu group with subsequent disulfide formation without any
      difficulty. This strategy using the StBu group in combination with the widely
      used acetamidomethyl (Acm), 4-methylbenzyl/4-methoxybenzyl (Meb/Mob), and trityl
      (Trt) groups enables reliable and regioselective synthesis of multicystine
      peptides. 

PMID- 25860513
TI  - Lack of GDAP1 induces neuronal calcium and mitochondrial defects in a knockout
      mouse model of charcot-marie-tooth neuropathy.
AB  - Mutations in GDAP1, which encodes protein located in the mitochondrial outer
      membrane, cause axonal recessive (AR-CMT2), axonal dominant (CMT2K) and
      demyelinating recessive (CMT4A) forms of Charcot-Marie-Tooth (CMT) neuropathy.
      Loss of function recessive mutations in GDAP1 are associated with decreased
      mitochondrial fission activity, while dominant mutations result in impairment of
      mitochondrial fusion with increased production of reactive oxygen species and
      susceptibility to apoptotic stimuli. GDAP1 silencing in vitro reduces Ca2+ inflow
      through store-operated Ca2+ entry (SOCE) upon mobilization of endoplasmic
      reticulum (ER) Ca2+, likely in association with an abnormal distribution of the
      mitochondrial network. To investigate the functional consequences of lack of
      GDAP1 in vivo, we generated a Gdap1 knockout mouse. The affected animals
      presented abnormal motor behavior starting at the age of 3 months.
      Electrophysiological and biochemical studies confirmed the axonal nature of the
      neuropathy whereas histopathological studies over time showed progressive loss of
      motor neurons (MNs) in the anterior horn of the spinal cord and defects in
      neuromuscular junctions. Analyses of cultured embryonic MNs and adult dorsal root
      ganglia neurons from affected animals demonstrated large and defective
      mitochondria, changes in the ER cisternae, reduced acetylation of cytoskeletal
      alpha-tubulin and increased autophagy vesicles. Importantly, MNs showed reduced
      cytosolic calcium and SOCE response. The development and characterization of the
      GDAP1 neuropathy mice model thus revealed that some of the pathophysiological
      changes present in axonal recessive form of the GDAP1-related CMT might be the
      consequence of changes in the mitochondrial network biology and mitochondria
      endoplasmic reticulum interaction leading to abnormalities in calcium
      homeostasis. 

PMID- 25860515
TI  - Posterior epidural migration of lumbar intervertebral disc fragment.

PMID- 25860516
TI  - Osteoporosis in acute fractures of the cervical spine: the role of opportunistic
      CT screening.
AB  - OBJECT: Recently published data make it possible to generate estimates of bone
      mineral density (BMD) by using CT attenuation; this innovation can save time and
      reduce costs. Although advanced age is associated with reduced BMD, especially in
      patients with a fracture of C-2, relatively few patients ever undergo formal dual
      x-ray absorptiometry studies. To the authors' knowledge, this is the first study
      to assess the utility of this technique in elucidating BMD in patients with an
      acute fracture of the cervical spine. METHODS: Patients who presented to a Level
      I trauma center with an acute fracture of the cervical spine and underwent
      abdominal (or L-1) CT scanning either at admission or in the 6 months before or
      after the injury were evaluated. Using a picture-archiving and communication
      system, the authors generated regions of interest of similar size in the body of
      L-1 (excluding the cortex) and computed mean values for CT attenuation. The
      values derived were compared with threshold values, which differentiate between
      osteoporotic and nonosteoporotic states; age-stratified groups were also
      compared. RESULTS: Of the 91 patients whose data were reviewed, 51 were < 65
      years old (mean 43.2 years) and 40 were >= 65 years old (mean 80.9 years). The
      overall mean CT attenuation values (in Hounsfield units [HU]), stratified
      according to age, were 193.85 HU for the younger cohort and 117.39 HU for the
      older cohort; the result of a comparison between these two values was significant
      (p < 0.001). CONCLUSIONS: Using opportunistic CT scanning, this study
      demonstrates the relative frequency of osteoporosis in acute fractures of the
      cervical spine. It also objectively correlates overall BMD with the known higher
      frequency of C-2 fractures in older patients. This technique harnesses the
      presence of opportunistic CT scans of the abdomen, which potentially reduces the
      need for the extra time and cost that may be associated with dual x-ray
      absorptiometry scanning.

PMID- 25860517
TI  - A comprehensive assessment of the risk of bone morphogenetic protein use in
      spinal fusion surgery and postoperative cancer diagnosis.
AB  - The risk of postoperative cancer following the use of recombinant human bone
      morphogenetic protein (BMP)-2 in spinal fusion is one potential complication that
      has received significant interest. Until recently, there has been little clinical
      evidence to support the assertion of potential cancer induction after BMP use in
      spinal surgery. This report aims to summarize the findings from clinical data
      available to date from the Yale University Open Data Access (YODA) project as
      well as more recently published large database studies regarding the association
      of BMP use in spinal fusion and the risk of postoperative cancer. A detailed
      review was based on online databases, primary studies, FDA reports, and
      bibliographies of key articles for studies that assessed the efficacy and safety
      of BMP in spinal fusion. In an analysis of the YODA project, one meta-analysis
      detected a statistically significant increase in cancer occurrence at 24 months
      but not at 48 months, and the other meta-analysis did not detect a significant
      increase in postoperative cancer occurrence. Analysis of 3 large health care data
      sets (Medicare, MarketScan, and PearlDiver) revealed that none were able to
      detect a significant increase in risk of malignant cancers when BMP was used
      compared with controls. The potential risk of postoperative cancer formation
      following the use of BMP in spinal fusion must be interpreted on an individual
      basis for each patient by the surgeon. There is no conclusive evidence that
      application of the common formulations of BMP during spinal surgery results in
      the formation of cancer locally or at a distant site. 

PMID- 25860518
TI  - Correction of clivoaxial angle deformity in the setting of suboccipital
      craniectomy: technical note.
AB  - A subset of patients with Chiari Type I malformation may develop neurological
      dysfunction secondary to an abnormally obtuse clivoaxial angle (CXA) and
      clivoaxial deformity causing deformative stress injury to the neural axis.
      Clivoaxial deformity can occur after initial standard suboccipital craniectomy,
      duraplasty, and C-1 laminectomy for brainstem compression, or severe clivoaxial
      deformity may be present in conjunction with a Chiari malformation. Clivoaxial
      deformity and abnormal CXA can be treated with an occipitocervical fusion (OCF).
      Performing OCF in the setting of a cranial defect can be challenging with
      currently available instrumentation. The authors describe their recent experience
      and outcomes in 3 consecutive pediatric patients using the "inside-out" technique
      for treating clivoaxial deformity and abnormal CXA in the setting of a
      craniectomy defect to restore stability to the craniocervical junction, while
      correcting the CXA. 

PMID- 25860520
TI  - Positive care? HIV and residential care for children in South Africa.
AB  - Responses to the HIV epidemic leading to an increase in the number of residential
      care facilities for children across sub-Saharan Africa have prompted concerns
      that large numbers of orphaned children are being placed in institutional care.
      There is little empirical research into the role that institutions are playing in
      the provision of care to children affected by HIV in the region. This paper draws
      on an exploratory study of the provision of residential care for children in the
      context of the HIV epidemic in South Africa. The analysis characterises the
      population of children in a small sample of residential care facilities in four
      provinces, and, after identifying a disproportionate number of HIV-positive
      children in care, examines the circumstances that led to their admission and the
      nature of HIV-related interventions in the facilities. The analysis reveals
      missed opportunities for non-institutional placements for HIV-positive children
      and identifies important gaps in the HIV prevention, treatment, care, and support
      interventions within the facilities. The article argues that a global and local
      preoccupation with orphans as being the children most severely affected by HIV,
      and as the primary category of children requiring alternative care as a result of
      the HIV epidemic, may have diverted attention away from the extent to which HIV
      positive children populate institutions in South Africa. Furthermore, we suggest
      that adjustments are required to both decision-making regarding placement of HIV
      positive children requiring alternative care and the provision of HIV-related
      interventions in residential facilities in order to ensure an adequate response
      to children's health and wellbeing. 

PMID- 25860521
TI  - HIV/AIDS fatalism, beliefs and prevention indicators in Gabon:comparisons between
      Gabonese and Malians.
AB  - HIV/AIDS fatalism may impact on individuals' health-seeking behaviour and HIV
      prevention efforts. This descriptive study measured levels of HIV/AIDS fatalism
      and documented HIV/AIDS beliefs and practices among a sample of Gabonese and
      Malians living in Gabon, West Africa. The Powe Fatalism Inventory-HIV/AIDS
      version was used to measure levels of fatalism, while a short-answer survey was
      used to document personal beliefs and behaviours related to HIV and AIDS among
      160 people in Gabon. The mean score of HIV/AIDS fatalism for the total sample was
      6.8 on a 15-point scale. Malians had a more fatalistic outlook than Gabonese
      (mean scores 9.4 versus 5.3), Muslims were more fatalistic than persons of other
      religions (mean scores 9.2 versus 5.3), while healthcare providers were less
      fatalistic than non-providers (mean scores 3.8 versus 7.4). People that did not
      believe that HIV/AIDS is a punishment from God had a lower mean score of fatalism
      than those who did. Most of the sample believed that AIDS is a real disease, and
      most did not think that only immoral people discuss HIV and AIDS. The HIV
      prevention indicators that related to lower scores of fatalism included knowing
      HIV-positive people, having had more years of formal education, a willingness to
      disclose one's HIV status (if known), and experience of HIV/AIDS education.
      Respondents who had tested for HIV were no less fatalistic than those who had
      never tested. The findings provide data from a part of the world where HIV/AIDS
      beliefs have rarely been documented. The results indicate a need for additional
      studies on correlations between HIV/ AIDS fatalism, HIV-prevention behaviours,
      and religious belief systems. 

PMID- 25860519
TI  - Postoperative infection in spine surgery: does the month matter?
AB  - OBJECT: The relationship between time of year and surgical site infection (SSI)
      following neurosurgical procedures is poorly understood. Authors of previous
      reports have demonstrated that rates of SSI following neurosurgical procedures
      performed during the summer months were higher compared with rates during other
      seasons. It is unclear, however, if this difference was related to climatological
      changes or inexperienced medical trainees (the July effect). The aim of this
      study was to evaluate for seasonal variation of SSI following spine surgery in a
      network of nonteaching community hospitals. METHODS: The authors analyzed 6 years
      of prospectively collected surveillance data (January 1, 2007, to December 31,
      2012) from all laminectomies and spinal fusions from 20 hospitals in the Duke
      Infection Control Outreach Network of community hospitals. Surgical site
      infections were defined using National Healthcare Safety Network criteria and
      identified using standardized methods across study hospitals. Regression models
      were then constructed using Poisson distribution to evaluate for seasonal trends
      by month. Each analysis was first performed for all SSIs and then for SSIs caused
      by specific organisms or classes of organisms. Categorical analysis was performed
      using two separate definitions of summer: June through September (definition 1),
      and July through September (definition 2). The prevalence rate of SSIs during the
      summer was compared with the prevalence rate during the remainder of the year by
      calculating prevalence rate ratios and 95% confidence intervals. RESULTS: The
      authors identified 642 SSIs following 57,559 neurosurgical procedures (overall
      prevalence rate = 1.11/100 procedures); 215 occurred following 24,466
      laminectomies (prevalence rate = 0.88/100 procedures), and 427 following 33,093
      spinal fusions (prevalence rate = 1.29/100 procedures). Common causes of SSI were
      Staphylococcus aureus (n = 380; 59%), coagulase-negative staphylococci (n = 90;
      14%), and Escherichia coli (n = 41; 6.4%). Poisson regression models demonstrated
      increases in the rates of SSI during each of the summer months for all SSIs and
      SSIs due to gram-positive cocci, S. aureus, and methicillin-sensitive S. aureus.
      Categorical analysis confirmed that the rate of SSI during the 4-month summer
      period was higher than the rate during the remainder of the year, regardless of
      which definition for summer was used (definition 1, p = 0.008; definition 2, p =
      0.003). Similarly, the rates of SSI due to grampositive cocci and S. aureus were
      higher during the summer months than the remainder of the year regardless of
      which definition of summer was used. However, the rate of SSI due to gram
      negative bacilli was not. CONCLUSIONS: The rate of SSI following fusion or spinal
      laminectomy/laminoplasty was higher during the summer in this network of
      community hospitals. The increase appears to be related to increases in SSIs
      caused by gram-positive cocci and, more specifically, S. aureus. Given the
      nonteaching nature of these hospitals, the findings demonstrate that increases in
      the rate of SSI during the summer are more likely related to ecological and/or
      environmental factors than the July effect.

PMID- 25860522
TI  - Dilemmas and tensions facing a faith-based organisation promoting HIVprevention
      among young people in South Africa.
AB  - Faith-based organisations (FBOs) are receiving growing attention for their roles
      in addressing HIV and AIDS in southern Africa. These roles, however, are not
      without philosophical challenges. Yet, to date, most references to the successes
      or limitations of FBOs have remained the domain of theoretical and, often,
      ideological debate. In this context, discussions about the roles of faith and
      FBOs in responding to HIV and AIDS often evoke extreme positions-either
      advocating for or critiquing their involvement. In place of this there is a need
      for empirical evidence and analyses that shed light on both the challenges and
      opportunities of faith-based HIV-prevention programming. This article presents a
      critical sociological analysis of the complexities confronting one FBO in its
      effort to deliver an abstinence-focused HIV-prevention programme to school-going
      adolescents in a poor peri-urban area of South Africa. As one aspect of a larger
      mixed-methods evaluation, this analysis is based on 11 focus group discussions,
      variously held with parents, teachers, learners and programme facilitators, in an
      effort to determine how and why the participants perceived the programme to work.
      We present and analyse four sources of tension appearing within the data which
      relate to the programme's faith-based orientation: a) enthusiasm for sexual
      abstinence despite awareness of the structural constraints; b) a dichotomous
      framing of behaviours (i.e. good versus bad); c) mixed messages about condoms;
      and d) administering faith-based programming within secular public schools.
      Through this analysis we aim to identify opportunities and challenges for faith
      based HIV-prevention efforts more broadly. We argue that any assessment of faith
      based HIV-prevention programming ought to respect and reflect its complexity as
      well as the complexity of the context within which it operates. 

PMID- 25860523
TI  - Assessing cognitive-linguistic abilities in South African adults living with HIV:
      the Cognitive Linguistic Quick Test.
AB  - HIV can cross the blood-brain barrier to enter the central nervous system. This
      results in cognitive deficits in the majority of patients. The assessment of
      these deficits and management of these patients poses challenges for healthcare
      workers in South Africa. This study investigates the effectiveness of the
      Cognitive Linguistic Quick Test (CLQT) in identifying the cognitive and
      linguistic abilities of adults with HIV or AIDS. Sixteen participants were
      recruited from an outpatient clinic in Johannesburg. The CLQT was utilised to
      assess the cognitive/linguistic abilities of the participants. The overall scores
      revealed that 87.5% of the participants presented with some form of cognitive
      deficit, 81% exhibited deficits in memory and executive functioning, 75% showed
      deficits in attention and visual perception, and 50% exhibited language deficits.
      Thus, this instrument may be usefully employed with patients who exhibit
      neurological disorders, including those caused by HIV infection. We conclude that
      the CLQT can be used as an alternative to more expensive, elaborate and time
      consuming neuropsychometric evaluations to identify deficits in memory, attention
      and executive functions as experienced by adults with HIV or AIDS in South
      Africa. 

PMID- 25860524
TI  - Mismatches between youth aspirations and participatory HIV/AIDSprogrammes in
      South Africa.
AB  - Although youth participation is a pillar of international HIV/AIDS policy, it is
      notoriously difficult to facilitate. We explore this challenge through a case
      study of a community-led HIV/AIDS management project in a South African rural
      area, in which anticipated youth participation failed to materialise. We take a
      social psychological view, examining ways in which opportunities offered by the
      project failed to resonate with the social identities and aspirations of local
      young people. Interviews and focus group discussions were conducted with 37 young
      people prior to the programme's establishment and with 21 young people four years
      later. In response to questions about what they wanted to achieve in life, the
      young people emphasized: career success through migrating to urban areas to seek
      education and paid work, non-tokenistic involvement in community affairs, and
      'having fun.' We look at how the project unintentionally evolved in ways that
      undermined these goals. Its strong local focus was inappropriately tailored to
      young people whose views of the future focused on getting away to urban areas as
      quickly as possible. The volunteer nature of the work held little appeal for
      ambitious young people who instead saw paid work as their way out of poverty and
      were reluctant to take unpaid time out from schoolwork. The project failed to
      develop new and democratic ways of operating-quickly becoming mired in
      traditional, adult-dominated social relations, in which young people with
      initiative and independent views were sometimes belittled by adults as being
      'smart' or 'clever.' Finally, the project's focus on sexual abstinence held
      little interest for young people who took an enthusiastic interest in sex. The
      article concludes with a discussion of the complexities of implementing youth
      friendly projects in communities steeped in top-down adult-dominated social
      interactions, and recommends ways in which similar projects might seek to involve
      youths more effectively. 

PMID- 25860525
TI  - Trend analysis and short-term forecast of incident HIV infection in Ghana.
AB  - The study uses time-series modelling to determine and predict trends in incident
      HIV infection in Ghana among specific age groups. The HIV data for Ghana were
      grouped according to northern and southern spatial sectors as they exhibited
      slightly different data collection formats. The trend of the epidemic is modelled
      using moving-average smoothing techniques, and the Box-Jenkins ARIMA model is
      used to forecast cases of newly acquired (incident) HIV infection. Trend analysis
      of past growth patterns reveals an increase in new cases of HIV infection in the
      northern sector, with the greatest increase occurring among persons aged 30 years
      and over. The epidemic in the southern sector appears to have levelled off.
      However, incident HIV infection in the 20-39-year-old age group of females in the
      sector is estimated to increase in the next three years. Moreover, the estimates
      suggest a higher increase in incident cases than that predicted by the National
      AIDS Control Programme. Nevertheless, incident HIV infection among persons aged
      19 and below is found to be relatively stable. Thus, if efforts are made to
      reduce or prevent an increase in the number of new infections in the northern
      sector, and for the 20-39 years age group in the southern sector, Ghana will have
      a brighter future with regard to its response to the HIV epidemic. These findings
      can assist with developing strategic-intervention policy planning for Ghana and
      other countries in sub-Saharan Africa. 

PMID- 25860526
TI  - HIV/AIDS messages as a spur for conversation among young South Africans?
AB  - HIV/AIDS messages are often deliberately puzzling so as to increase the chance
      for them to be used as food for conversation. The South African health
      organisation 'loveLife,' for instance, uses messages that include complicated
      rhetorical expressions in their media campaigns, reasoning that those who find
      the messages puzzling and wonder about their meaning will be inclined to discuss
      the messages with their peers. In order to test the assumption that puzzlement
      about health messages is related to keenness to talk about these messages,
      structured interviews were held with 30 black learners, ages 15 to 19, from
      Limpopo Province, South Africa, about the messages of six HIV/ AIDS posters and
      six HIV/AIDS radio advertisements from 'loveLife' or another South African health
      organisation. No support was found for the assumption that presenting a puzzling
      health message will contribute to engaging the recipients in discussion. The
      participants indicated that they were willing to discuss the themes addressed in
      either a poster or radio advertisement because they appreciated the message and
      felt that its content was relevant to them, rather than because the message was
      puzzling or difficult to understand. The participants' overall actual
      comprehension of the messages, however, proved to be strikingly low. 

PMID- 25860527
TI  - Deafness and HIV/AIDS: a systematic review of the literature.
AB  - A systematic review of the literature focused on empirical work on deafness and
      HIV/AIDS published during the past decade. The review reveals that deaf people
      are vulnerable to contracting HIV and might lack access to HIV/ AIDS information,
      testing and treatment. Three studies that were located through this review
      included prevalence data on disability and HIV. These indicated that deaf people
      are as likely, if not twice as likely, to be infected with HIV. The data also
      reveal that although some research has focused on HIV/AIDS knowledge among deaf
      people, this might not be the main area of concern in relation to HIV risk for
      this population. The available research more often points to increased instances
      of multiple partners, sexual abuse and earlier sexual debut, and, in some
      contexts, decreased use of condoms. These factors might explain increased risk of
      HIV infection for the deaf population. Additionally, the review elaborates on the
      geographical and methodological focuses of past research and identifies gaps,
      strengths and weaknesses in this body of literature. 

PMID- 25860528
TI  - Human-rights perspectives on caregiving of people with HIV: the case for the
      Kanye home-based care programme, Botswana.
AB  - The article discusses the human rights associated with caregiving to people with
      HIV or AIDS, based on empirical findings about a community home-based care
      programme in Kanye, Botswana. The study was explorative in nature and qualitative
      in design and used focus group discussions with caregivers and one-on-one
      interviews with nurses in the programme. The findings indicate that primary
      caregivers suffer various infringements on their human rights and regularly face
      dilemmas pertaining to inadequate access to their clients' medication and
      treatment, inadequate knowledge of their clients' sickness, lack of compensation
      in case of injury during caregiving, gender exploitation, inequality, stigma, and
      harsh working conditions often coupled with a heavy caseload. Having children
      leave school to carry out a caregiving role also represents an abuse of human
      rights. The researcher advocates anti-stigma and gender-empowering education,
      adequate treatment and medication for clients to facilitate caregiving, the
      formulation of policy that would allow caregivers information about their
      clients' sicknesses, improved caregiving conditions, and the discouragement of
      minors from leaving school to take on caregiving. 

PMID- 25860529
TI  - Using an absorbable purse-string suture to reduce surgical defects of the nose
      before placement of full-thickness skin grafts.

PMID- 25860530
TI  - Reflectance confocal microscopy features of a clonal seborrheic keratosis that
      clinically and dermoscopically simulates melanoma.

PMID- 25860531
TI  - Hypothalamic signaling mechanisms in hypertension.
AB  - The etiology of hypertension, a critical public health issue affecting one in
      three US adults, involves the integration of the actions of multiple organ
      systems, including the central nervous system. Increased activation of the
      central nervous system, driving enhanced sympathetic outflow and increased blood
      pressure, has emerged as a major contributor to the pathogenesis of hypertension.
      The hypothalamus is a key brain site acting to integrate central and peripheral
      inputs to ultimately impact blood pressure in multiple disease states that evoke
      hypertension. This review highlights recent advances that have identified novel
      signal transduction mechanisms within multiple hypothalamic nuclei (e.g.,
      paraventricular nucleus, arcuate nucleus) acting to drive the pathophysiology of
      hypertension in neurogenic hypertension, angiotensin II hypertension, salt
      sensitive hypertension, chronic intermittent hypoxia, and obesity-induced
      hypertension. Increased understanding of hypothalamic activity in hypertension
      has the potential to identify novel targets for future therapeutic interventions
      designed to treat hypertension. 

PMID- 25860532
TI  - European Society for Paediatric Infectious Diseases consensus recommendations for
      rotavirus vaccination in Europe: update 2014.
AB  - The first evidence-based recommendations for rotavirus (RV) vaccination in Europe
      were prepared at the time of licensure of 2 live oral RV vaccines (Rotarix,
      GlaxoSmithKline Biologicals, and RotaTeq, Sanofi Pasteur MSD) in 2006 and
      published in 2008. Since then several countries in Europe and more globally have
      adopted universal RV vaccination of all healthy infants as part of their national
      immunization programs (NIPs). The experience from these NIPs has produced a
      wealth of post-introduction effectiveness data that, together with the evidence
      from prelicensure efficacy trials presented in the 2008 Recommendations, support
      the case of RV vaccination in Europe. The prelicensure safety trials of Rotarix
      and RotaTeq, each in populations of more than 60,000 infants, did not reveal risk
      of intussusception (IS), but postvaccination surveillance in several countries,
      particularly Australia and Mexico, has established that the risk of IS for both
      vaccines after the first dose might be between 1:50,000 and 1:80,000. Although it
      may be argued that the risk is acceptable vis-a-vis the great benefits of RV
      vaccination, this argument alone may not suffice, and every effort should be made
      to reduce the risk of IS. Considerable evidence, including postvaccination
      surveillance data from Germany, suggests that the risk of IS can be reduced by
      early administration of the first dose of oral RV vaccine. The previous European
      Society for Paediatric Infectious Diseases/European Society for Paediatric
      Gastroenterology, Hepatology and Nutrition recommendations held that the first
      dose of oral RV vaccine should be given between 6 and 12 weeks of age; this
      recommendation is sustained but with an emphasis toward the lower range of the
      recommended age, that is, preferably between 6 and 8 weeks of age. At the time of
      the earlier recommendations, experience of RV vaccination in premature infants
      and other special target groups was limited. It is now recommended with greater
      confidence than before that prematurely born infants should be vaccinated
      according to their calendar age as recommended for full-term infants. It is now
      strongly recommended that all HIV-infected or HIV-exposed infants should be
      vaccinated with oral RV vaccine. Although specific information on many
      immunodeficiencies is lacking, infants with known severe combined
      immunodeficiency should not receive live RV vaccine. 

PMID- 25860533
TI  - Importance of Enhanced Surveillance for Prevention of Pertussis in Children.
AB  - BACKGROUND: Bordetella pertussis infection causes considerable morbidity, even in
      countries with high vaccination coverage. Surveillance of pertussis is usually
      passive and based on mandatory reporting. We assessed the epidemiologic and
      clinical characteristics of pertussis cases detected by passive or enhanced
      surveillance. METHODS: A prospective population-based study was carried out from
      January 2012 to December 2013 in Catalonia and Navarre, 2 Spanish regions with a
      total population of 8.2 million. For each confirmed case, variables of age, sex,
      clinical symptoms, laboratory results and vaccination status were investigated.
      Associations between the variables studied and the type of surveillance were
      assessed by odds ratio (OR) and its 95% confidence interval (CI). Logistic
      regression was used to estimate adjusted OR (aOR). RESULTS: In children <18 years
      of age, passive surveillance was the most important source of detection (95.7% in
      <1 year). In children 5-10 years of age, passive surveillance detected 67.5% of
      cases. In those >=18 years, enhanced surveillance was the most frequent source of
      case detection (82.5%). Inspiratory whoop (aOR: 1.94; 95% CI: 1.40-2.70), apnea
      (aOR: 1.92; 95% CI: 1.28-2.87) and posttussive vomiting (aOR: 1.43; 95% CI: 1.04
      1.96) were symptoms included in the clinical case definition that were associated
      with passive surveillance. CONCLUSIONS: Underreporting of symptomatic cases is
      important not only in adults, but also in children >1 year of age and suggests
      that providing clinics with free, fast laboratory diagnostic tests, together with
      enhanced surveillance of family contacts of any age is necessary to better
      determine existing cases. Enhanced surveillance may be helpful to better
      understand transmission patterns in the family and in the community.

PMID- 25860534
TI  - Infectious Disease-related Emergency Department Visits Among Children in the US.
AB  - BACKGROUND: Although most research on infectious diseases (IDs) has focused on
      hospitalizations, this provides an incomplete picture of healthcare utilization.
      We describe the burden and epidemiologic features of ID-related emergency
      department (ED) visits among U.S. children. METHODS: We conducted a cross
      sectional analysis of the Nationwide Emergency Department Sample, a nationally
      representative sample of ED patients. We identified children who presented to the
      ED with a primary diagnosis of ID. Outcome measures were ID-related ED visits,
      hospitalizations through the ED and ED charges. RESULTS: During 2011, we
      identified 1,914,509 ID-related ED visits among U.S. children, corresponding to a
      weighted estimate of 8,524,357 ED visits. This accounted for 28% of all ED visits
      by children. The frequency of ID-related ED visits was 10,290 visits per 100,000
      children. The most common diagnoses were upper respiratory infection (41%),
      otitis media (18%) and lower respiratory infection (14%). Overall, 62% of ID
      related ED visits were made by children with Medicaid; 35% were by those in the
      lowest income quartile. Among the ID-related ED visits, 424,725 (5%) resulted in
      hospitalization, with 513 hospitalizations per 100,000 children. The most common
      reason for hospitalization was lower respiratory infection, which accounted for
      40% of all ID-related hospitalizations from the ED. Median charge per ED visit
      was $718, with total annual charges of $9.6 billion. CONCLUSIONS: The public
      health burden of IDs, as measured by ED visits, subsequent hospitalizations and
      associated charges, was substantial. We also found that children with markers of
      lower socioeconomic status comprised a disproportionately high proportion of ID
      related ED visits.

PMID- 25860535
TI  - Vitamin D sufficiency and Staphylococcus aureus infection in children.
AB  - Vitamin D promotes epithelial immunity by upregulating antimicrobial peptides,
      including LL-37, which have bactericidal activity against Staphylococcus aureus.
      We found that children with vitamin D deficiency or insufficiency [25
      hydroxyvitamin D <30 ng/mL] were more likely to present with recurrent, rather
      than primary, S. aureus skin or soft tissue infection. Vitamin D sufficiency may
      be one of a myriad of host and environmental factors that can be directly
      impacted to reduce the frequency of S. aureus skin and soft tissue infection. 

PMID- 25860536
TI  - Clinical Analysis of 134 Children with Nervous System Damage Caused by
      Enterovirus 71 Infection.
AB  - OBJECTIVE: The purpose of this study was to evaluate the clinical characteristics
      of nervous system damage caused by enterovirus 71 (EV71) infection in pediatric
      patients. STUDY DESIGN: Clinical data and outcomes were retrospectively analyzed
      for 134 cases of laboratory confirmed pediatric EV71 infection admitted to the
      Children's Hospital of Chongqing Medical University from January to December
      2013. RESULTS: EV71 infection was significantly more common in patients 1-4 years
      of age, in males and during the months of April-July. Fifty-six cases complicated
      by hand, foot and mouth disease were diagnosed. Fever was the most common symptom
      (128 of 134 patients) and lasted on average 5.3 +/- 2.1 days. The most common
      neurologic complication was aseptic meningitis (n = 74), followed by brain stem
      encephalitis (n = 24), acute flaccid paralysis (AFP; n = 20), acute
      parencephalitis (n = 12) and encephalomyelitis (n = 4). Each was characterized by
      a unique profile of clinical symptoms. Damage to the pons and medulla oblongata
      was apparent in 28 brain magnetic resonance images. Lesions associated with AFP
      were concentrated in the cervical spinal cord and thoracic 8. The anterior root
      of the spinal anterior horn was a specific lesion. Fourteen of the AFP patients
      had unilateral or bilateral femoral nerve involvement. None of the patients died,
      and in 132 of 134 patients, follow-up visits showed that their physical and
      neuropsychologic abilities had returned to normal. CONCLUSIONS: Most children
      infected with EV71 have a good prognosis if they are diagnosed early and receive
      proper supportive treatment.

PMID- 25860538
TI  - The use of urinary bladder matrix in the treatment of complicated open wounds.
AB  - BACKGROUND: Management of complicated open wounds represents a challenge when
      reconstructive options are not applicable. Urinary bladder matrix (UBM) provides
      a biocompatible material that allows inductivetissue remodeling. METHODS: The use
      of urinary bladder matrix inthe treatment of 5 patients with complicated open
      wounds that failed toheal with conventional therapy is presented. RESULTS: A 3
      year old male sustained a second-degree oil burn measuring 8 cm x 4 cm to his
      dorsal forearm; UBM was applied weekly and the wound epithelialized in 3 weeks. A
      52-year old male sustained massive second and third degree burns to his leg after
      a fire; UBM was applied weekly and the wound epithelialized in 28 weeks. A 61
      year old female sustained a severe crushing injury to her right knee. A
      gastrocnemius muscle transfer and rectus abdominus muscle free flap transfer both
      failed, then UBM and vacuum-assisted closure therapy were applied and the wound
      epithelialized in 24 weeks. A 54-year old female underwent a breast mastectomy
      and immediate reconstruction with pedicled transverse rectus abdominus flap. The
      patient developed partial necrosis and the wound was managed with UBM and vacuum
      assisted closure therapy. The wound epithelialized in 12 weeks. A 36-year old
      female sustained severe degloving injuries to both hands with exposed
      metacarpals. Weekly application of UBM provided tissue remodeling over the bones,
      which allowed successful skin grafting and closure. CONCLUSIONS: These
      experiences show UBM to be an effective method in management of complicated open
      wounds in select cases. Further studies need to be implemented to confirm this
      conclusion.

PMID- 25860537
TI  - Sphingosin-1-phosphate Receptor 1: a Potential Target to Inhibit
      Neuroinflammation and Restore the Sphingosin-1-phosphate Metabolism.
AB  - BACKGROUND: Recent evidence suggests that an extreme shift may occur in
      sphingosine metabolism in neuroinflammatory contexts. Sphingosine 1-phosphate
      (S1P)-metabolizing enzymes (SMEs) regulate the level of S1P. We recently found
      that FTY720, a S1P analogue, and SEW2871, a selective S1P receptor 1 (S1P1)
      agonist, provide protection against neural damage and memory deficit in amyloid
      beta (Abeta)-injected animals. This study aimed to evaluate the effects of these
      two analogues on the expression of SMEs as well as their anti-inflammatory roles.
      METHODS: Rats were treated with intracerebral lipopolysaccharide (LPS) or Abeta.
      Memory impairment was assessed by Morris water maze and the effects of drugs on
      SMEs as well as inflammatory markers, TNF- alpha and COX-II, were determined by
      immunoblotting. RESULTS: Abeta and LPS differentially altered the expression
      profile of SMEs. In Abeta-injected animals, FTY720 and SEW2871 treatments exerted
      anti-inflammatory effects and restored the expression profile of SMEs, in
      parallel to our previous findings. In LPS animals however, in spite of anti
      inflammatory effects of the two analogues, only FTY720 restored the levels of
      SMEs and prevented memory deficit. CONCLUSION: The observed ameliorating effects
      of FTY720 and SEW7821 can be partly attributed to the interruption of the vicious
      cycle of abnormal S1P metabolism and neuro-inflammation. The close imitation of
      the FTY720 effects by SW2871 in Abeta-induced neuro-inflammation may highlight
      the attractive role of S1P1 as a potential target to restore S1P metabolism and
      inhibit inflammatory processes.

PMID- 25860539
TI  - Development of a miniature mass spectrometer with continuous atmospheric pressure
      interface.
AB  - The demand for on-the-spot analysis is met by a miniature mass spectrometer which
      is preferred to be robust, stable, as small as possible and capable of analyzing
      different samples by coupling with various ionization methods. However, largely
      constrained by the atmospheric pressure interface (API), these aspects are
      difficult to be realized in one system. Herein, we describe the development of a
      new miniature mass spectrometer with balanced performance. The miniature mass
      spectrometer is small in size (30 * 30 * 18 cm) but has a continuous API, which
      was achieved by high-pressure ion trap operation and maximized ion transfer
      efficiency with the utilization of a differential pumping system. The miniature
      mass spectrometer was characterized and optimized in terms of stability,
      sensitivity, mass range, mass resolution and scan speed. Rapid analysis of
      mixtures was demonstrated by coupling the miniature mass spectrometer with the
      ambient ionization technique of paper spray. This is the smallest miniature mass
      spectrometer to date, which has a continuous API. 

PMID- 25860540
TI  - PIGS: improved estimates of identity-by-descent probabilities by probabilistic
      IBD graph sampling.
AB  - Identifying segments in the genome of different individuals that are identical-by
      descent (IBD) is a fundamental element of genetics. IBD data is used for numerous
      applications including demographic inference, heritability estimation, and
      mapping disease loci. Simultaneous detection of IBD over multiple haplotypes has
      proven to be computationally difficult. To overcome this, many state of the art
      methods estimate the probability of IBD between each pair of haplotypes
      separately. While computationally efficient, these methods fail to leverage the
      clique structure of IBD resulting in less powerful IBD identification, especially
      for small IBD segments. 

PMID- 25860542
TI  - Isolation and characterization of endophytic plant growth-promoting bacteria from
      date palm tree (Phoenix dactylifera L.) and their potential role in salinity
      tolerance.
AB  - Endophytic bacteria were isolated from date palm (Phoenix dactylifera L.)
      seedling roots, characterized and tested for their ability to help plants grow
      under saline conditions. Molecular characterization showed that the majority of
      these strains belonged to the genera Bacillus and Enterobacter and had different
      degrees of resistance to various antibiotics. Some of these strains were able to
      produce the enzyme 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase and the
      plant growth regulatory hormone indole-3-acetic acid (IAA). Some strains were
      also able to chelate ferric iron (Fe(3+)) and solubilize potassium (K(+)),
      phosphorus (PO 4 (3-) ) and zinc (Zn(2+)), and produce ammonia. The results also
      showed that ACC deaminase activity and IAA production was slightly increased in
      some strains in response to an increase in NaCl concentration in the growth
      media. Consistent with these results, selected strains such as PD-R6
      (Paenibacillus xylanexedens) and PD-P6 (Enterobacter cloacae) were able to
      enhance canola root elongation when grown under normal and saline conditions as
      demonstrated by a gnotobiotic root elongation assay. These results suggest that
      the isolated and characterized endophytic bacteria can alter ethylene and IAA
      levels and also facilitate nutrient uptake in roots and therefore have the
      potential role to promote the growth and development of date palm trees growing
      under salinity stress. 

PMID- 25860543
TI  - Evidence for bactericidal activities of lipidic nanoemulsions against Pseudomonas
      aeruginosa.
AB  - Pseudomonas aeruginosa has been implicated in a broad range of infections and
      shown to acquire rapid resistance to anti-microbial agents. In the present, study
      we have used particular amalgamation of specific lipids that hold innate
      antibacterial activities, which can be transformed into cationized and non
      cationized nanoemulsions. The anti-Pseudomonas activities were then elucidated by
      transmission/scanning electron microscopy, and atomic force microscopy. The
      microscopic studies revealed the cell lysis due to the formation of blebs,
      exudation of essential cellular contents and loss of characteristics contour of
      the cells. The microscopic studies were then corroborated by zone of inhibition,
      cytoplasmic release studies, time dependent killing and MIC determination.
      Conclusively, it can be inferred that the delivery issues of antibiotics could be
      reassessed by using certain excipients that possess inherent antibacterial
      properties. This will not only avoid unnecessary introduction of inactive
      excipients in the body, but will also reduce the dose of antibiotics because of
      synergistic effects of excipients and drug acting together. 

PMID- 25860545
TI  - Identifying regional service function from PM2.5 mass concentration throughout a
      city with non-negative tensor factorization approach.
AB  - This paper examines the holistic viewpoint on pollution pattern from time, day,
      and region dimensions based on the public data of fine particle concentrations,
      which cover 35 ambient monitoring stations in Beijing firstly. According to data
      driven, non-negative tensor factorization (NTF) method is introduced to
      distinguish pollution patterns which could identify the area service function.
      Results show that five patterns are obtained and annotated as traffic,
      industrial, residential, commercial, and steady ones. Each type owns special
      characteristics on time basis or day basis. Furthermore, calculating the
      reconstruction correlation of tensors with respect to sites, time, and days
      approximately approaches to 0.95-0.96, and it can be employed with high
      evaluation values of the model. Comparing with the original classifications drew
      by land use, this method corresponds with the reality well for considering the
      changes of surrounding sources. Some commendations on public travel and
      controlling measures based on local pollution presented in this study can be
      provided for further decrease of fine particle and improvement of air quality.

PMID- 25860544
TI  - Discovery of a Small-Molecule Probe for V-ATPase Function.
AB  - Lysosomes perform a critical cellular function as a site of degradation for
      diverse cargoes including proteins, organelles, and pathogens delivered through
      distinct pathways, and defects in lysosomal function have been implicated in a
      number of diseases. Recent studies have elucidated roles for the lysosome in the
      regulation of protein synthesis, metabolism, membrane integrity, and other
      processes involved in homeostasis. Complex small-molecule natural products have
      greatly contributed to the investigation of lysosomal function in cellular
      physiology. Here we report the discovery of a novel, small-molecule modulator of
      lysosomal acidification derived from diversity-oriented synthesis through high
      content screening. 

PMID- 25860546
TI  - Impact of wastewater on fish health: a case study at the Neckar River (Southern
      Germany) using biomarkers in caged brown trout as assessment tools.
AB  - The present work describes a field survey aiming at assessing the impact of a
      sewage treatment plant (STP) effluent on fish health by means of biomarkers.
      Indigenous fish were absent downstream of the STP. To elucidate the reason behind
      this, brown trout (Salmo trutta f. fario) were exposed in floating steel cages up
      and downstream of a STP located at the Neckar River near Tubingen (Southern
      Germany), for 10 and 30 days. A combination of biomarker methods
      (histopathological investigations, analysis of the stress protein Hsp70,
      micronucleus test, B-esterase assays) offered the possibility to investigate
      endocrine, geno-, proteo- and neurotoxic effects in fish organs. Biological
      results were complemented with chemical analyses on 20 accumulative substances in
      fish tissue. Even after short-term exposure, biomarkers revealed clear evidence
      of water contamination at both Neckar River sites; however, physiological
      responses of caged brown trout were more severe downstream of the STP. According
      to this, similar bioaccumulation levels (low MUg/kg range) of DDE and 12
      polycyclic aromatic hydrocarbons (PAHs) were detected at both sampling sites,
      while up to fourfold higher concentrations of four PAHs, methyl-triclosan and two
      synthetic musks occurred in the tissues of downstream-exposed fish. The results
      obtained in this study suggest a constitutive background pollution at both sites
      investigated at the Neckar River and provided evidence for the additional
      negative impact of the STP Tubingen on water quality and the health condition of
      fish.

PMID- 25860547
TI  - Thermodynamic analysis of fatty acid harvesting by novel carbon-based adsorbent.
AB  - In this study, separation and concentration of fatty acids (FA) from the
      synthetic food processing wastewater containing low concentration of FA (250
      mg/L) were investigated using expanded graphite (EG) as a novel adsorbent at
      different temperatures (298~318 K). The adsorption results were further analyzed
      to verify adsorption mechanisms and thermodynamics of FA onto EG. Results show
      that the adsorption of FA onto EG was explained well by the Langmuir model with
      the maximum adsorption capacity up to 8.01 g FA/g EG at 298 K, and considerably
      affected by temperature. The adsorption kinetics fitted with pseudo-second-order
      kinetic model and the adsorption mechanism analysis showed that the intraparticle
      diffusion was not the rate-limiting step, but the coalescence of FA droplets
      played the significant role for novel adsorption of FA onto EG. The calculated
      activation energy and thermodynamic parameters such as Gibbs free energy change
      (DeltaG(0)), enthalpy change (DeltaH(0)), and entropy change (DeltaS(0))
      indicated that the adsorption of FA onto EG was very feasible, was highly
      spontaneous, occurred physically, was exothermic in nature, and was stable in
      aquatic environmental changes. Overall, FA can be effectively harvested and
      concentrated from the food processing wastewater by EG even at low concentration.

PMID- 25860548
TI  - Influences of key factors on manganese release from soil of a reservoir shore.
AB  - In the summertime, the manganese pollution in moderately deep lakes and
      reservoirs caused by thermal stratification processes has been a serious problem.
      To mitigate the issue, understanding the key factors that control manganese
      releases from reservoir soils is a critical step. To this end, batch experiments
      and the response surface methodology (RSM) analysis were conducted in this study
      to investigate the release of Mn(diss) and Mn(III) (0.45 MUm filterable) from
      soil samples collected along a reservoir shore under different combined effects
      of pH, dissolved oxygen (DO), temperature, and dissolved organic carbon (DOC).
      According to the three-dimensional (3-D) response surfaces plotted from the
      mathematical model, the highest concentrations of Mn(diss) and Mn(III) released
      from the studied soils were achieved when the release process was carried out at
      30.0  degrees C using a citric acid solution (10.8 mg/L) of pH 6.0 with the DO
      concentration of 0.0 mg/L. It was found that pH was the most significant factor
      affecting the release of Mn(diss) and Mn(III) among the four factors. The
      combined effect of pH and DOC was also very significant to stimulate Mn(III)
      releases. In addition, both Mn(diss) and Mn(III) followed the same release
      principle under the coupled effects of the four factors. A close agreement
      between experimental and predicted values from the developed models was found.

PMID- 25860549
TI  - Identification of low-Cd cultivars of sweet potato (Ipomoea batatas (L.) Lam.)
      after growing on Cd-contaminated soil: uptake and partitioning to the edible
      roots.
AB  - Cadmium (Cd) contamination in agricultural products presents a threat to humans
      when consumed. Sweet potato is the world's seventh most important food crop. The
      aims of this study were to screen for low-Cd sweet potato cultivars and clarify
      the mechanisms of low-Cd accumulation in edible roots. A pot experiment was
      conducted to investigate the variation of Cd uptake and translocation among 30
      sweet potato cultivars grown in contaminated soils with three different Cd
      concentrations. Cadmium concentrations in edible roots were significantly
      different among cultivars and were significantly affected by Cd treatment, and
      the interaction between cultivar and Cd treatment. High-Cd cultivars have higher
      ratios of edible root/shoot Cd concentration and edible root/feeder root Cd
      concentration than low-Cd cultivars; however, the ratio of shoot/feeder root Cd
      concentration seems unrelated to the ability of Cd accumulation in edible roots.
      Four sweet potato cultivars, Nan88 (No. 10), Xiang20 (No. 12), Ji78-066 (No. 15),
      and Ji73-427 (No. 16), were identified as low-Cd cultivars. Cadmium translocation
      from feeder roots to edible roots via the xylem, and from shoots to edible roots
      via the phloem, controls Cd accumulation in edible roots of sweet potato
      cultivars. 

PMID- 25860551
TI  - Erratum to: Acetylcholinesterase in zebrafish embryos as a tool to identify
      neurotoxic effects in sediments.

PMID- 25860550
TI  - The characteristics of phenanthrene biosorption by chemically modified biomass of
      Phanerochaete chrysosporium.
AB  - The natural (S0) and chemically modified Phanerochaete chrysosporium including
      the methylation of amino groups (S1), acetylation of hydroxyl groups (S2), lipid
      removal (S3), esterification of carboxyl groups (S4), and base hydrolysis (S5)
      were characterized, and their sorption for phenanthrene (PHE) was investigated.
      The sorption isotherm of PHE on natural biomasses was apparently linear, while it
      was nonlinear for the modified ones. The partition coefficient (K d ) describing
      the sorption affinity of PHE by biomasses followed the order of S0 (9.24 L g(-1))
      > S5 (8.94 L g(-1)) > S1 (7.13 L g(-1)) > S2 (6.97 L g(-1)) > S3 (6.38 L g(-1)) >
      S4 (3.51 L g(-1)) and decreased as temperature increased. The PHE adsorption
      fitted well to the pseudo-second-order kinetic model, and the sorption capacity
      was in the order of S5 (2041.5 MUg g(-1)) > S0 (1768.8 MUg g(-1)) > S2 (1570.9
      MUg g(-1)) > S1 (1552.9 MUg g(-1)) > S3 (1346.4 MUg g(-1)) > S4 (991.0 MUg g(
      1)). Moreover, the pi-pi and electron donor-acceptor interactions may govern PHE
      sorption which processed spontaneously and exothermally. The natural and modified
      biomasses, especially the base hydrolysis treated ones, were economical and
      effective biosorbents for PHE removal.

PMID- 25860552
TI  - Factors controlling nitrous oxide emissions from a full-scale activated sludge
      system in the tropics.
AB  - Despite interest in characterizing nitrous oxide (N2O) emissions from wastewater
      treatment plants (WWTPs) in several parts of the globe, there are few studies in
      tropical zones. This study focus on the contribution of the scientific knowledge
      of anthropogenic nitrogen greenhouse gas emissions to climate change in tropical
      countries, investigating factors controlling N2O emissions in a non-biological
      nitrogen removal municipal WWTP. In terms of operational parameters, dissolved
      oxygen (DO) concentrations displayed a biphasic impact on N2O production and
      emission, with the highest emission at DO of 2.0 mg O2 L(-1). The low solids
      retention time of 3 days also played a significant role, leading to nitrite
      accumulation, which is an important trigger for N2O production during
      nitrification. Furthermore, other factor especially important for tropical
      countries, namely, temperature, also had a positive correlation with N2O
      production. Emission factors estimated for this study were 0.12 (0.02-0.31)% of
      the influent total nitrogen load and 8.1 (3-17) g N2O person(-1) year(-1), 2.5
      times higher than currently proposed emission factors. Therefore, the highly
      variability and dependence on operational parameters reinforce the use of a
      single emission factor is inadequate, especially for developing countries with
      limited or variable extent of biological wastewater treatment and in regions of
      the world with widely varying climate patterns.

PMID- 25860553
TI  - Biodegradation of pesticides using fungi species found in the aquatic
      environment.
AB  - Relatively limited attention has been given to the presence of fungi in the
      aquatic environment compared to their occurrence in other matrices. Taking
      advantage and recognizing the biodegradable capabilities of fungi is important,
      since these organisms may produce many potent enzymes capable of degrading toxic
      pollutants. Therefore, the aim of this study was to evaluate the potential
      ability of some species of filamentous fungi that occur in the aquatic
      environment to degrade pesticides in untreated surface water. Several laboratory
      scale experiments were performed using the natural microbial population present
      in the aquatic environment as well as spiked fungi isolates that were found to
      occur in different water matrices, to test the ability of fungi to degrade
      several pesticides of current concern (atrazine, diuron, isoproturon and
      chlorfenvinphos). The results obtained in this study showed that, when spiked in
      sterile natural water, fungi were able to degrade chlorfenvinphos to levels below
      detection and unable to degrade atrazine, diuron and isoproturon. Penicillium
      citrinum, Aspergillus fumigatus, Aspergillus terreus and Trichoderma harzianum
      were found to be able to resist and degrade chlorfenvinphos. These fungi are
      therefore expected to play an important role in the degradation of this and other
      pollutants present in the aquatic environment. 

PMID- 25860554
TI  - Variation of levels and distribution of N-nitrosamines in different seasons in
      drinking waters of East China.
AB  - We surveyed the occurrence of nine N-nitrosamine species in ten bottled drinking
      waters from supermarket and other water samples including raw waters, finished
      waters, and distribution system waters from nine municipal drinking water
      treatment plants in eight cities of Jiangsu Province, East China. N
      nitrosodimethylamine (NDMA) was detected in one of ten bottled drinking water
      samples at concentration of 4.8 ng/L and N-nitrosomorpholine (NMor) was detected
      in four of the ten bottles with an average concentration and a standard deviation
      of 16 +/- 15 ng/L. The levels of nitrosamines in the distribution system water
      samples collected during summer season ranged from below detection limit (BDL) to
      5.4 ng/L for NDMA, BDL to 9.5 ng/L for N-nitrosomethylethylamine (NMEA), BDL to
      2.7 ng/L for N-nitrosodiethylamine (NDEA) and BDL to 8.5 ng/L for N
      nitrosopyrrolidine (NPyr). Samples of distribution system waters collected in
      winter season had levels of nitrosamines ranged from BDL to 45 ng/L for NDMA, BDL
      to 5.2 ng/L for NPyr, and BDL to 309 ng/L for N-nitrosopiperidine (NPip). A
      positive correlation of the concentration of NDMA as well as the total nine N
      nitrosamines between finished waters and distribution system waters was observed.
      Both dissolved organic carbon and nitrite were found to correlate linearly with N
      nitrosamine levels in raw waters.

PMID- 25860555
TI  - Comparative proteome analysis of multi-layer cocoon of the silkworm, Bombyx mori.
AB  - Bombyx mori cocoon has a multi-layer structure that provides optimal protection
      for silkworm pupa. Research on the mechanical properties of the multi-layer
      structure revealed structure-property relationships of the cocoon. Here, we
      investigated the protein components of the B. mori cocoon in terms of its multi
      layer structure. Liquid chromatography-tandem mass spectrometry identified 286
      proteins from the multiple cocoon layers. In addition to fibroins and sericins,
      we identified abundant protease inhibitors, seroins and proteins of unknown
      function. By comparing protein abundance across layers, we found that the
      outermost layer contained more sericin1 and protease inhibitors and the innermost
      layer had more seroin1. As many as 36 protease inhibitors were identified in
      cocoons, showing efficient inhibitory activities against a fungal protease. Thus,
      we propose that more abundant protease inhibitors in the outer cocoon layers may
      provide better protection for the cocoon. This study increases our understanding
      of the multi-layer mechanism of cocoons, and helps clarify the biological
      characteristics of cocoons. The data have been deposited to the ProteomeXchange
      with identifier PXD001469. 

PMID- 25860556
TI  - Long-term Cost-effectiveness of Statin Treatment for Primary Prevention of
      Cardiovascular Disease in the Elderly.
AB  - PURPOSE: This study aimed to evaluate the cost-effectiveness of statins for
      primary prevention of stroke and myocardial infarction (MI) in the elderly in
      Singapore. METHODS: A Markov model was developed to investigate the lifetime
      costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness
      ratios (ICERs) of statin treatment in those aged 65 years and older without a
      history of stroke or MI from the perspective of Singapore's healthcare system,
      using elderly-specific clinical data and local costs from hospital databases. A
      lifetime horizon was used and all costs and health outcomes were discounted at 3%
      annually. RESULTS: In the base-case analysis, statin treatment prevented an
      additional four strokes and eight MIs among 1,000 "healthy" elderly individuals
      compared with no treatment. Statin treatment resulted in a QALY gain of 0.26 and
      additional costs of SGD 11,314 per person, yielding an ICER of SGD 43,925 (USD
      33,495) per QALY gained. The results were sensitive to statin effectiveness,
      particularly statins' effect on all-cause mortality, and cost of statin
      medication. Probabilistic sensitivity analysis demonstrated that the probability
      of statin treatment being cost-effective was 72% at a willingness-to-pay
      threshold of SGD 65,000 (USD 49,546) per QALY gained. Shortening the time horizon
      from lifetime to 10 years (simulating limited life expectancy) considerably
      increased the ICER to SGD 291,313 (USD 167,171) per QALY. Female gender and
      younger age were also associated with higher ICERs owing to a lower baseline risk
      of cardiovascular disease (CVD) and higher costs to manage events in these
      subgroups. CONCLUSIONS: Statin treatment for the primary prevention of CVD in the
      elderly was cost-effective. However, treatment warrants re-evaluation when the
      prognosis of the individual is considered less than ten years; other goals may
      take precedence over CVD prevention.

PMID- 25860557
TI  - Correlation Between SNPs in Candidate Genes and VerifyNow-Detected Platelet
      Responsiveness to Aspirin and Clopidogrel Treatment.
AB  - PURPOSE: Patients with high on-treatment platelet reactivity (HPR) against
      aspirin or clopidogrel are at increased risk for adverse cardiovascular events.
      In this study, we explored the predictive value of common SNPs for the on
      treatment platelet reactivity (OPR) against aspirin and clopidogrel assessed by
      VerifyNow assays. METHODS: This study recruited 286 Han Chinese individuals
      undergoing antiplatelet treatment, including 159 cases with aspirin only (100
      mg/day) and 127 cases with dual therapy (aspirin 100 mg/day plus clopidogrel 75
      mg/day) for at least 2 weeks. The OPR against aspirin and clopidogrel were
      assessed by VerifyNow Aspirin (ARU) and P2Y12 assays (PRU), respectively.
      Genotyping for the selected 25 SNPs within 11 genes and 2 GWAS loci was carried
      out by ABI multiplex SNaPshot method. RESULTS: The results indicated that
      rs4244285 (CYP2C19) and rs342293 (7q22.3) were significantly associated with PRU
      value (both P < 0.01). As for the OPR to aspirin, a weak statistical significance
      was observed in rs5445 (GNB3) (P = 0.049) and rs5758 (TBXA2R) (P = 0.045). After
      adjusting for the covariates including gender, age and smoking, carriers of
      allele A of rs4244285 remained as a strong predictor for HPR against clopidogrel.
      CONCLUSION: The current study suggests that common SNPs may predict OPR against
      clopidogrel as assessed by VerifyNow P2Y12, but are less likely to respond
      against aspirin as assessed by VerifyNow Aspirin.

PMID- 25860559
TI  - Disruption of zinc and copper interactions with Abeta(1-40) by a non-toxic,
      isoniazid-derived, hydrazone: a novel biometal homeostasis restoring agent in
      Alzheimer's disease therapy?
AB  - Disruptions of biometal-Abeta(1-40) interactions by an isoniazid-derived
      hydrazone, INHHQ, were demonstrated via in vitro NMR titrations. The compound has
      adequate theoretical BBB absorption properties, assessed by in silico studies. In
      vivo acute toxicity assays indicate that INHHQ is innocuous up to 300 mg kg(-1),
      showing potential as an anti-Alzheimer's drug. 

PMID- 25860558
TI  - Sequential superresolution imaging of multiple targets using a single
      fluorophore.
AB  - Fluorescence superresolution (SR) microscopy, or fluorescence nanoscopy, provides
      nanometer scale detail of cellular structures and allows for imaging of
      biological processes at the molecular level. Specific SR imaging methods, such as
      localization-based imaging, rely on stochastic transitions between on
      (fluorescent) and off (dark) states of fluorophores. Imaging multiple cellular
      structures using multi-color imaging is complicated and limited by the differing
      properties of various organic dyes including their fluorescent state duty cycle,
      photons per switching event, number of fluorescent cycles before irreversible
      photobleaching, and overall sensitivity to buffer conditions. In addition,
      multiple color imaging requires consideration of multiple optical paths or
      chromatic aberration that can lead to differential aberrations that are important
      at the nanometer scale. Here, we report a method for sequential labeling and
      imaging that allows for SR imaging of multiple targets using a single fluorophore
      with negligible cross-talk between images. Using brightfield image correlation to
      register and overlay multiple image acquisitions with ~10 nm overlay precision in
      the x-y imaging plane, we have exploited the optimal properties of AlexaFluor647
      for dSTORM to image four distinct cellular proteins. We also visualize the
      changes in co-localization of the epidermal growth factor (EGF) receptor and
      clathrin upon EGF addition that are consistent with clathrin-mediated
      endocytosis. These results are the first to demonstrate sequential SR (s-SR)
      imaging using direct stochastic reconstruction microscopy (dSTORM), and this
      method for sequential imaging can be applied to any superresolution technique. 

PMID- 25860560
TI  - In memory of Dr. Jose Geraldo Vernet Taborda (1951-2014).

PMID- 25860561
TI  - Biomarkers and staging of bipolar disorder: a systematic review.
AB  - INTRODUCTION: A growing body of evidence suggests that bipolar disorder (BD) is a
      progressive disease according to clinical, biochemical and neuroimaging findings.
      This study reviewed the literature on the relationship between specific
      biomarkers and BD stages. METHODS: A comprehensive literature search of MEDLINE
      and PubMed was conducted to identify studies in English and Portuguese using the
      keywords biomarker, neurotrophic factors, inflammation, oxidative stress,
      neuroprogression and staging models cross-referenced with bipolar disorder.
      RESULTS: Morphometric studies of patients with BD found neuroanatomic
      abnormalities, such as ventricular enlargement, grey matter loss in the
      hippocampus and cerebellum, volume decreases in the prefrontal cortex and
      variations in the size of the amygdala. Other studies demonstrated that serum
      concentrations of neurotrophic factors, inflammatory mediators and oxidative
      stress may be used as BD biomarkers. CONCLUSIONS: The analysis of neurobiological
      changes associated with BD progression and activity may confirm the existence of
      BD biomarkers, which may be then included in staging models that will lead to
      improvements in treatment algorithms and more effective, individually tailored
      treatment regimens. Biomarkers may also be used to define early interventions to
      control disease progression.

PMID- 25860562
TI  - Resilience of caregivers of people with dementia: a systematic review of
      biological and psychosocial determinants.
AB  - INTRODUCTION: Although caregivers of people with dementia may face difficulties,
      some positive feelings of caregiving may be associated with resilience.
      OBJECTIVE: This study systematically reviewed the definitions, methodological
      approaches and determinant models associated with resilience among caregivers of
      people with dementia. METHODS: Search for articles published between 2003 and
      2014 in ISI, PubMed/MEDLINE, SciELO and Lilacs using the search terms resilience,
      caregivers and dementia. RESULTS AND CONCLUSIONS: Resilience has been defined as
      positive adaptation to face adversity, flexibility, psychological well-being,
      strength, healthy life, burden, social network and satisfaction with social
      support. No consensus was found about the definition of resilience associated
      with dementia. We classified the determinant variables into biological,
      psychological and social models. Higher levels of resilience were associated with
      lower depression rates and greater physical health. Other biological factors
      associated with higher levels of resilience were older age, African-American
      ethnicity and female sex. Lower burden, stress, neuroticism and perceived control
      were the main psychological factors associated with resilience. Social support
      was a moderating factor of resilience, and different types of support seemed to
      relieve the physical and mental overload caused by stress.

PMID- 25860563
TI  - Phenomenological aspects of the cognitive rumination construct.
AB  - OBJECTIVE: To evaluate the importance of phenomenological aspects of the
      cognitive rumination (CR) construct in current empirical psychiatric research.
      METHOD: We searched SciELO, Scopus, ScienceDirect, MEDLINE, OneFile (GALE),
      SpringerLink, Cambridge Journals and Web of Science between February and March of
      2014 for studies whose title and topic included the following keywords: cognitive
      rumination; rumination response scale; and self-reflection. The inclusion
      criteria were: empirical clinical study; CR as the main object of investigation;
      and study that included a conceptual definition of CR. The studies selected were
      published in English in biomedical journals in the last 10 years. Our
      phenomenological analysis was based on Karl Jaspers' General Psychopathology.
      RESULTS: Most current empirical studies adopt phenomenological cognitive elements
      in conceptual definitions. However, these elements do not seem to be carefully
      examined and are indistinctly understood as objective empirical factors that may
      be measured, which may contribute to misunderstandings about CR, erroneous
      interpretations of results and problematic theoretical models. CONCLUSION:
      Empirical studies fail when evaluating phenomenological aspects of the cognitive
      elements of the CR construct. Psychopathology and phenomenology may help define
      the characteristics of CR elements and may contribute to their understanding and
      hierarchical organization as a construct. A review of the psychopathology
      principles established by Jasper may clarify some of these issues.

PMID- 25860564
TI  - Variation of plasma cortisol levels in patients with depression after treatment
      with bilateral electroconvulsive therapy.
AB  - INTRODUCTION: More than 60 years after the introduction of modern
      psychopharmacology, electroconvulsive therapy (ECT) continues to be an essential
      therapeutic modality in the treatment of mental disorders, but its mechanism of
      action remains unclear. Hormones play an essential role in the development and
      expression of a series of behavioral changes. One aspect of the influence of
      hormones on behavior is their potential contribution to the pathophysiology of
      psychiatric disorders and the mechanism of action of psychotropic drugs and ECT.
      OBJECTIVE: We measured blood levels of the hormone cortisol in patients with
      unipolar depression according to the Diagnostic and Statistical Manual of Mental
      Disorders, 4th edition (DSM-IV) and compared results with levels found in healthy
      adults. METHOD: Blood cortisol levels were measured before the beginning of
      treatment with ECT, at the seventh session, and at the last session, at treatment
      completion. Depression symptoms were assessed using the Beck Depression Inventory
      (BDI). RESULTS: Cortisol levels remained stable in both men and women between the
      seventh and the last sessions of ECT; values ranged from 0.686+/-9.6330 g/dL for
      women, and there was a mean decrease of 5.825+/-6.0780 g/dL (p = 0.024). Mean
      number of ECT sessions was 12. After the seventh and the last ECT sessions,
      patients with depression and individuals in the control group had similar
      cortisol levels, whereas BDI scores remained different. CONCLUSION: Cortisol
      levels decreased during ECT treatment. ECT seems to act as a regulator of the
      hypothalamic-pituitaryadrenal axis.

PMID- 25860565
TI  - Cross-cultural adaptation of the Spence children's anxiety scale in Malaysia.
AB  - INTRODUCTION: Anxiety among children has increased in recent years. Culturally
      adapted questionnaires developed to measure the level of anxiety are the best
      screening instruments for the general population. This study describes the
      scientific translation and adaptation of the Spence Children's Anxiety Scale
      (SCAS) into the Malay language. METHOD: The process of scientific translation of
      this selfreport instrument followed the guidelines of the Task Force for
      Translation and Cultural Adaptation of the International Society for
      Pharmacoeconomics and Outcomes Research (ISPOR). RESULTS: The Malay version and
      its adaptation for a new cultural context are described. CONCLUSION: The Malay
      version achieved the aims of the original version and its conceptual and
      operational equivalence. It may be used as the first Malay instrument to measure
      anxiety among children in research and in clinical and community settings.

PMID- 25860566
TI  - Translation and cross-cultural adaptation of the Brazilian Portuguese version of
      the driving anger scale (DAS): long form and short form.
AB  - INTRODUCTION: Driving anger has attracted the attention of researchers in recent
      years because it may induce individuals to drive aggressively or adopt risk
      behaviors. The Driving Anger Scale (DAS) was designed to evaluate the propensity
      of drivers to become angry or aggressive while driving. This study describes the
      cross-cultural adaptation of a Brazilian version of the short form and the long
      form of the DAS. METHODS: Translation and adaptation were made in four steps: two
      translations and two back-translations carried out by independent evaluators; the
      development of a brief version by four bilingual experts in mental health and
      driving behaviors; a subsequent experimental application; and, finally, an
      investigation of operational equivalence. RESULTS: Final Brazilian versions of
      the short form and of the long form of the DAS were made and are presented.
      CONCLUSIONS: This important instrument, which assesses driving anger and
      aggressive behaviors, is now available to evaluate the driving behaviors of the
      Brazilian population, which facilitates research in this field.

PMID- 25860567
TI  - Managing severe behavioral symptoms of a patient with anti-NMDAR encephalitis:
      case report and findings in current literature.
AB  - OBJECTIVE: Psychiatric symptoms emerge in the early stages of anti-N-methyl-D
      aspartate receptor (anti-NMDAR) encephalitis, and patients often seek treatment
      in psychiatric departments before visiting any other general medical services.
      Numerous articles about anti-NMDAR encephalitis have been published in the
      scientific community worldwide, but few emphasize the role of psychiatry in
      symptom management. CASE DESCRIPTION: We describe the case of a patient with anti
      -NMDAR encephalitis seen in our service and discuss the management of behavioral
      symptoms based on current scientific literature. High doses of atypical
      antipsychotics and benzodiazepines were used to control agitation, and trazodone
      was administered to treat insomnia. COMMENTS: Consultation-liaison psychiatry may
      help the healthcare team adjust the management of neuropsychiatric complications
      that might affect inpatients with anti-NMDAR encephalitis.

PMID- 25860568
TI  - Psychophysiological responses to Salsa dance.
AB  - Speculation exists whether dance provides physiological stimuli adequate to
      promote health and fitness benefits. Unfortunately, research to date has not
      addressed the affective and exertional responses to dance. These responses are of
      interest as positive affective and exertional responses experienced during
      physical activity may play an important role in predicting adherence. The present
      study aims to examine the psychophysiological responses of different Salsa dance
      styles. Ten pairs of dancers performed two different structured lessons of Salsa
      dance, including Typical Salsa and Rueda de Casino lessons, and a non-structured
      Salsa dance at a night club. Physiological responses (i.e., percent of heart rate
      reserve; %HRR) were continuously assessed and perceived exertion and affective
      valence were rated every 15 min throughout the trials. %HRR responses differed
      between the Salsa dance styles (%HRR from 41.3 to 51.9%), and participants were
      dancing at intensities near their ventilatory threshold. Specifically, Typical
      Salsa lesson elicited lower %HRR responses than Rueda de Casino lesson (p <
      0.05), but similar %HRR responses to Salsa dance at a night club condition (p >
      0.05). Surprisingly, exertional (from 8 to 11) and affective (from +3 to +5)
      responses were unaffected by Salsa dance styles (p > 0.05). These data support
      that different Salsa dance styles provide physiological stimuli adequate to
      promote health and fitness benefits, and perhaps more importantly, produce
      pleasurable experiences, which in turn might lead to an increase in adherence to
      Salsa dancing which likely provides exercise-like health benefits. 

PMID- 25860569
TI  - Control, elimination, and eradication of river blindness: scenarios, timelines,
      and ivermectin treatment needs in Africa.
AB  - River blindness (onchocerciasis) causes severe itching, skin lesions, and vision
      impairment including blindness. More than 99% of all current cases are found in
      sub-Saharan Africa. Fortunately, vector control and community-directed treatment
      with ivermectin have significantly reduced morbidity. Studies in Mali and Senegal
      proved the feasibility of elimination with ivermectin administration. The
      treatment goal is shifting from control to elimination in endemic African
      regions. Given limited resources, national and global policymakers need a
      rigorous analysis comparing investment options. For this, we developed scenarios
      for alternative treatment goals and compared treatment timelines and drug needs
      between the scenarios. Control, elimination, and eradication scenarios were
      developed with reference to current standard practices, large-scale studies, and
      historical data. For each scenario, the timeline when treatment is expected to
      stop at country level was predicted using a dynamical transmission model, and
      ivermectin treatment needs were predicted based on population in endemic areas,
      treatment coverage data, and the frequency of community-directed treatment. The
      control scenario requires community-directed treatment with ivermectin beyond
      2045 with around 2.63 billion treatments over 2013-2045; the elimination
      scenario, until 2028 in areas where feasible, but beyond 2045 in countries with
      operational challenges, around 1.48 [corrected] billion treatments; and the
      eradication scenario, lasting until 2040, around 1.30 billion treatments. The
      eradication scenario is the most favorable in terms of the timeline of the
      intervention phase and treatment needs. For its realization, strong health
      systems and political will are required to overcome epidemiological and political
      challenges.

PMID- 25860570
TI  - aPKC phosphorylation of HDAC6 results in increased deacetylation activity.
AB  - The Class II histone deacetylase, HDAC6, has been shown to be involved in cell
      motility, aggresome formation and mitochondria transport. HDAC6 deacetylase
      activity regulates alpha-tubulin acetylation levels and thus plays a critical
      role in these processes. In turn, HDAC6 activity can be regulated by interaction
      with various proteins including multiple kinases. Kinase mediated phosphorylation
      of HDAC6 can lead to either increased or reduced activity. Our previous research
      has shown that sequestosome1/p62 (SQSTM1/p62) interacts with HDAC6 and regulates
      its activity. As SQSTM1/p62 is a scaffolding protein known to interact directly
      with the zeta isoform of Protein Kinase C (PKCzeta), we sought to examine if
      HDAC6 could be a substrate for PKCzeta phosphorylation and if so, how its
      activity might be regulated. Our data demonstrate that HDAC6 is not only present
      in a protein complex with PKCzeta but can also be phosphorylated by PKCzeta. We
      also show that specific phosphorylation of HDAC6 by PKCzeta increases HDAC6
      deacetylase activity resulting in reduced acetylated tubulin levels. Our findings
      provide novel insight into the molecular mechanism by which HDAC6, PKCzeta and
      SQSTM1/p62 function together in protein aggregate clearance. These results also
      highlight a new research direction which may prove fruitful for understanding the
      underlying cause of several neurodegenerative diseases. 

PMID- 25860571
TI  - Correction: LATS1 and LATS2 phosphorylate CDC26 to modulate assembly of the
      tetratricopeptide repeat subcomplex of APC/C.

PMID- 25860572
TI  - Flooding and mental health: a systematic mapping review.
AB  - BACKGROUND: Floods are the most common type of global natural disaster. Floods
      have a negative impact on mental health. Comprehensive evaluation and review of
      the literature are lacking. OBJECTIVE: To systematically map and review available
      scientific evidence on mental health impacts of floods caused by extended periods
      of heavy rain in river catchments. METHODS: We performed a systematic mapping
      review of published scientific literature in five languages for mixed studies on
      floods and mental health. PUBMED and Web of Science were searched to identify all
      relevant articles from 1994 to May 2014 (no restrictions). RESULTS: The
      electronic search strategy identified 1331 potentially relevant papers. Finally,
      83 papers met the inclusion criteria. Four broad areas are identified: i) the
      main mental health disorders-post-traumatic stress disorder, depression and
      anxiety; ii] the factors associated with mental health among those affected by
      floods; iii) the narratives associated with flooding, which focuses on the long
      term impacts of flooding on mental health as a consequence of the secondary
      stressors; and iv) the management actions identified. The quantitative and
      qualitative studies have consistent findings. However, very few studies have used
      mixed methods to quantify the size of the mental health burden as well as
      exploration of in-depth narratives. Methodological limitations include control of
      potential confounders and short-term follow up. LIMITATIONS: Floods following
      extreme events were excluded from our review. CONCLUSIONS: Although the level of
      exposure to floods has been systematically associated with mental health
      problems, the paucity of longitudinal studies and lack of confounding controls
      precludes strong conclusions. IMPLICATIONS: We recommend that future research in
      this area include mixed-method studies that are purposefully designed, using more
      rigorous methods. Studies should also focus on vulnerable groups and include
      analyses of policy and practical responses.

PMID- 25860574
TI  - The NMatrix, a new method of presenting statistics, displays the characteristics
      of medicines with similar effects used in the treatment of lumbar spinal stenosis
      concisely and clearly, facilitating the selection of appropriate medications.
AB  - BACKGROUND: It is often difficult to compare the characteristics of a medicine
      with those of others based on common standards, whereas the application of
      rational standards would be expected to facilitate the comparison of medicines
      with similar effects. The present study was conducted to clarify the
      characteristics of individual medicines and to examine whether rational standards
      allow the most appropriate medicines to be chosen. METHODS: Participants
      diagnosed with lumbar spinal stenosis (LSS) were assessed for QOL and ADL based
      on the Roland-Morris Disability Questionnaire, JOA score, VAS, and the presence
      of intermittent claudication (IC). Four medicines--beraprost sodium, ethyl
      icosapentate (EPA), sarpogrelate hydrochloride, and limaprost alfadex (PGE1)-
      were prescribed in a random manner. These four medicines were assessed
      independently in four studies using the same study design and size in each case.
      Using the NMatrix, the characteristics of the four medicines and the results of
      mutual comparisons could be displayed concisely and clearly in one matrix based
      on significance levels. This work involved analyzing pooled data from the four
      studies. RESULTS: All four medicines improved IC--one of the characteristic
      symptoms of LSS--by 12 weeks after administration. PGE1 required more time than
      the other medicines to affect IC. EPA appeared to almost significantly ameliorate
      some items at every point, though the evidence was insufficient. CONCLUSIONS: The
      NMatrix concisely and clearly displays the characteristics of "medicines with
      similar effects" for the treatment of lumbar spinal stenosis, and can help
      physicians to choose the optimal medicine based on rational criteria for
      individual patients, according to their symptoms and progress.

PMID- 25860573
TI  - TLR4/NF-kappaB signaling contributes to chronic unpredictable mild stress-induced
      atherosclerosis in ApoE-/- mice.
AB  - OBJECTIVE: Chronic stress is an important risk factor for atherosclerotic
      diseases. Our previous studies have shown that chronic unpredictable mild stress
      (CUMS) accelerates atherosclerosis and up-regulates TLR4/NF-kappaB expression in
      apoE-/- mice. However, TLR4/NF-kappaB signaling whether directly contributes to
      the development of atherosclerosis in CUMS mice is unclear. We hypothesized that
      the interference of TLR4/NF-kappaB can ameliorate CUMS-induced inflammation and
      atherosclerosis in apoE-/- mice. METHODS: ApoE-/- mice were exposed to 12 weeks
      CUMS. Ad-siRNA TLR4 was given by tail vein injection (10 MUl/mouse, every 5
      days), and PDTC (an inhibitor of NF-kappaB) was given by intraperitoneal
      injection (60 mg/kg, once a day). Plasma corticosterone concentrations were
      determined by solid-phase 125I radioimmunoassay. Atherosclerosis lesions in
      aortic sinuses were evaluated and quantified by IMAGEPRO PLUS. Western blotting
      was used to detect the expression of TLR4, NF-kappaB, and IL-1beta in aortas of
      the mice. Plasma lipid profiles, IL-1beta, TNF-alpha, and MCP-1 were measured by
      ELISA. RESULTS: Our results indicated that CUMS apoE-/- mice treatment with siRNA
      TLR4 significantly decreased atherosclerosis and down-regulated TLR4, NF-kappaB,
      and inflammatory cytokines. PDTC also remarkably reduced atherosclerosis and the
      levels of IL-1beta, TNF-alpha and MCP-1 in plasma. However, Treatment with siRNA
      TLR4 or PDTC had no effect on plasma corticosterone levels, and lipid profiles.
      CONCLUSIONS: TLR4/NF-kappaB pathway may participate in CUMS-induced
      atherosclerosis through activation of proinflammatory cytokines in apoE-/- mice.
      Our data may provide a new potential therapeutic target for prevention of CUMS 
      induced atherosclerosis.

PMID- 25860575
TI  - The current status and future of radiotherapy for spinal bone metastases.
AB  - The management of spinal bone metastases is complex. In this review, the
      efficacy, methodology, and utilization of radiotherapy (RT) for spinal bone
      metastases are discussed. A number of randomized trials have evaluated the
      efficacy of 8 Gy, single-fraction RT for the palliation of painful bone
      metastases. However, RT for metastatic spinal cord compression has not been
      evaluated with respect to its optimal dose, palliative potential, or its ability
      to improve motor function. Two highly sophisticated RT techniques - stereotactic
      body RT (SBRT) and intensity-modulated RT (IMRT) - have recently been adapted for
      the treatment of spinal bone metastases, and both have the potential to achieve
      excellent control while minimizing acute and late toxicity. SBRT and IMRT are
      particularly well suited for the treatment of spinal bone metastases when they
      are localized or require re-irradiation, and may provide superior tumor control.
      Predicting the prognosis of patients with bone metastases and assessing spinal
      instability are both important when selecting the optimal RT method and deciding
      whether to perform surgery. The proper care of spinal bone metastases patients
      requires an interdisciplinary treatment approach.

PMID- 25860577
TI  - New trends in ultrasound of hepatosplenic sarcoidosis.

PMID- 25860578
TI  - Fasciolosis.
AB  - Fasciolosis is a zoonosis affecting ruminants, caused by the liver flukes
      Fasciola (F.) hepatica, and F. gigantica, which infect at least 2.4 million
      people worldwide. This disease may occur in cluster or family infections or after
      travel in high-risk areas such as the Nile Delta in Egypt, Iran, Turkey, South
      East Asia, Mexico, the Caribbean and the Andean Altiplano. In Europe, fasciolosis
      occurs more frequently in Portugal, Spain and France, although autochthonous
      infections have also been reported from Ireland and Germany. Infectious
      metacercariae are ingested with contaminated water or raw or undercooked
      vegetables. During their larval stage immature flukes migrate through the liver
      producing an acute febrile syndrome some weeks after infection, followed by a
      chronic-latent stage which may last for years or decades. Acute fasciolosis is
      characterized by fever, high eosinophilia and hepatosplenomegaly. At this stage
      ova are usually not yet produced. Diagnosis relies on the detection of specific
      antibodies and/or antigens in serum. Typical imaging features include multiple,
      ill-defined, fleeting hypodense or hypoechoic areas in the liver. Intraabdominal
      bleeding due to fluke's penetration of the bowel wall or liver capsule, may
      occur. In chronic latent fasciolosis the diagnosis is achieved by specific
      serology tests, detection of eggs in bile and parasitological examinations of
      multiple enriched stools samples. Ultrasonography may sometimes reveal a dilated
      and thickened common bile duct or crescent-like parasites in the gallbladder or
      bile ducts. Some patients exhibit sludge which typically does not sediment.
      Triclabendazole at a single dose of 10  mg/kg body weight is the treatment of
      choice.

PMID- 25860576
TI  - Clinical applications of gene therapy for primary immunodeficiencies.
AB  - Primary immunodeficiencies (PIDs) have represented a paradigmatic model for
      successes and pitfalls of hematopoietic stem cells gene therapy. First clinical
      trials performed with gamma retroviral vectors (gamma-RV) for adenosine deaminase
      severe combined immunodeficiency (ADA-SCID), X-linked SCID (SCID-X1), and Wiskott
      Aldrich syndrome (WAS) showed that gene therapy is a valid therapeutic option in
      patients lacking an HLA-identical donor. No insertional mutagenesis events have
      been observed in more than 40 ADA-SCID patients treated so far in the context of
      different clinical trials worldwide, suggesting a favorable risk-benefit ratio
      for this disease. On the other hand, the occurrence of insertional oncogenesis in
      SCID-X1, WAS, and chronic granulomatous disease (CGD) RV clinical trials prompted
      the development of safer vector construct based on self-inactivating (SIN)
      retroviral or lentiviral vectors (LVs). Here we present the recent results of LV
      mediated gene therapy for WAS showing stable multilineage engraftment leading to
      hematological and immunological improvement, and discuss the differences with
      respect to the WAS RV trial. We also describe recent clinical results of SCID-X1
      gene therapy with SIN gamma-RV and the perspectives of targeted genome editing
      techniques, following early preclinical studies showing promising results in
      terms of specificity of gene correction. Finally, we provide an overview of the
      gene therapy approaches for other PIDs and discuss its prospects in relation to
      the evolving arena of allogeneic transplant. 

PMID- 25860579
TI  - Impact of revisions of the JSCCR guidelines on the treatment of T1 colorectal
      carcinomas in Japan.
AB  - PURPOSE: In 1977, the Japanese Society for Cancer of the Colon and Rectum (JSCCR)
      published the first edition of the general guidelines that described how to
      record clinical and histopathological findings of colorectal carcinomas (CRCs)
      and how to treat these cancers, and since then, the guidelines were revised
      several times. The aim of this study was to examine the impact of the revisions
      of the JSCCR guidelines on the treatment of submucosal CRCs (T1-CRCs) in Japanese
      clinical settings. METHODS: Questionnaires were sent to all 391 member
      institutions of the JSCCR. The questionnaires consisted of 2 parts: details of
      the institutions and treatment strategies for T1-CRCs. RESULTS: 73 (19 %)
      institutions responded to the survey. The number of treated T1-CRCs has increased
      year by year, and the rate of endoscopic resection for T1-CRCs has significantly
      increased with revisions of the guidelines (1417 [47 %] of 2985 T1-CRCs in 2003 -
      2005, 2110 [50 %] of 4212 in 2006 - 2008, and 2546 [54 %] of 4686 in 2009 - 2011,
      P<.05). CONCLUSION: The revisions of the JSCCR guidelines have influenced the
      treatment of T1-CRCs in Japanese clinical settings. There is room to revise the
      criteria for curative endoscopic resection to avoid unnecessary surgeries.

PMID- 25860580
TI  - [Langerhans cell histiocytosis of the stomach with BRAF-V600E-mutation: case
      report and review of the literature].
AB  - Langerhans cell histiocytosis is a disease with different clinical presentations
      and a wide spectrum of organ involvements. Rarely Langerhans cell histiocytosis
      can involve the gastrointestinal tract of adult patients. A case of infiltration
      of gastric mucosa by Langerhans cell histiocytosis is presented. The neoplastic
      nature of this infiltrate is underlined by the detection of a BRAF-V600E
      mutation. Additionally, an overview of the so far 5 cases published in the
      English literature is provided. The published clinical experience indicates a
      benign curse of the disease. 

PMID- 25860581
TI  - [Abdominal ultrasonography in patients with diabetes mellitus. Part 1: Liver].
AB  - In patients with diabetes mellitus, abdominal ultrasonography is the appropriate
      diagnostic technique to detect and to follow-up secondary and accompanying
      diseases of the liver, the kidneys, the pancreas, the gastrointestinal tract and
      of abdominal vessels. Moreover, pancreatic and hepatic diseases may be realized
      which are of etiological importance for diabetes mellitus. Based on a systematic
      survey of the published literature, this review in 3 parts will describe the
      value of abdominal ultrasonography in patients with diabetes mellitus. Part 1
      deals with the diagnostic relevance and particular findings of ultrasonographic
      methods in hepatic manifestations and complications of diabetes mellitus. 

PMID- 25860582
TI  - [Noncardiac chest pain (NCCP) in German chest pain units].

PMID- 25860583
TI  - [Pancreatic cancer stroma: oncologist's ally or foe?].

PMID- 25860584
TI  - Cemeteries are effective sites for monitoring la crosse virus (LACv) and these
      environments may play a role in LACv infection.
AB  - La Crosse encephalitis (LAC) is the leading arboviral disease among children, and
      was previously limited to the upper Midwest. In 2012 nine pediatric cases of LAC
      occurred in eastern Tennessee, including one fatal case. In an attempt to
      identify sites near an active LACv infection and describe the abundance and
      distribution of potential LACv vectors near a fatal LAC case in the Appalachian
      region, we initiated an end of season study using a combination of questing and
      oviposition mosquito traps placed at forty-nine sites consisting of cemeteries
      and houses within 16 radial kilometers of two pediatric infections. LACv was
      isolated from three Aedes triseriatus pools collected from cemeteries and spatial
      clustering analysis identified clusters of Ae. triseriatus and Ae. albopictus
      populations that overlapped in the same area as the 2012 LACv cases. Results
      indicate cemeteries are effective sites for monitoring LACv. The role of
      cemeteries and specific environmental features will be the focus of future
      investigations. 

PMID- 25860586
TI  - Ru(II)-Catalyzed beta-Carboline Directed C-H Arylation and Isolation of Its
      Cycloruthenated Intermediates.
AB  - A Ru(II)-catalyzed C-H arylation approach has been developed utilizing beta
      carboline alkaloids as the directing group. Selective formations of diarylated
      products from moderate to excellent yields were accomplished. Broad substrate
      scope with excellent functional group tolerance for C1-phenyl/thienyl/PAHs-beta
      carbolines was demonstrated. X-ray crystal structure of cycloruthenated complex
      2cr and no arylation reaction with model substrate 13 strongly suggests that N2
      is the directing group than N9 in C1-aryl-beta-carbolines. Catalytic properties
      and stability of the cycloruthenated complexes have been explored. Library of
      biologically relevant new beta-carboline derivatives and isolation of its
      cycloruthenated intermediates are the highlights of this work. 

PMID- 25860585
TI  - A quaternary mechanism enables the complex biological functions of octameric
      human UDP-glucose pyrophosphorylase, a key enzyme in cell metabolism.
AB  - In mammals, UDP-glucose pyrophosphorylase (UGP) is the only enzyme capable of
      activating glucose-1-phosphate (Glc-1-P) to UDP-glucose (UDP-Glc), a metabolite
      located at the intersection of virtually all metabolic pathways in the mammalian
      cell. Despite the essential role of its product, the molecular basis of UGP
      function is poorly understood. Here we report the crystal structure of human UGP
      in complex with its product UDP-Glc. Beyond providing first insight into the
      active site architecture, we describe the substrate binding mode and
      intermolecular interactions in the octameric enzyme that are crucial to its
      activity. Importantly, the quaternary mechanism identified for human UGP in this
      study may be common for oligomeric sugar-activating nucleotidyltransferases.
      Elucidating such mechanisms is essential for understanding nucleotide sugar
      metabolism and opens the perspective for the development of drugs that
      specifically inhibit simpler organized nucleotidyltransferases in pathogens. 

PMID- 25860587
TI  - Regularity of cardiac rhythm as a marker of sleepiness in sleep disordered
      breathing.
AB  - AIM: The present study aimed to analyse the autonomic nervous system activity
      using heart rate variability (HRV) to detect sleep disordered breathing (SDB)
      patients with and without excessive daytime sleepiness (EDS) before sleep onset.
      METHODS: Two groups of 20 patients with different levels of daytime sleepiness 
      sleepy group, SG; alert group, AG- were selected consecutively from a Maintenance
      of Wakefulness Test (MWT) and Multiple Sleep Latency Test (MSLT) research
      protocol. The first waking 3-min window of RR signal at the beginning of each nap
      test was considered for the analysis. HRV was measured with traditional linear
      measures and with time-frequency representations. Non-linear measures 
      correntropy, CORR; auto-mutual-information function, AMIF- were used to describe
      the regularity of the RR rhythm. Statistical analysis was performed with non
      parametric tests. RESULTS: Non-linear dynamic of the RR rhythm was more regular
      in the SG than in the AG during the first wakefulness period of MSLT, but not
      during MWT. AMIF (in high-frequency and in Total band) and CORR (in Total band)
      yielded sensitivity > 70%, specificity >75% and an area under ROC curve > 0.80 in
      classifying SG and AG patients. CONCLUSION: The regularity of the RR rhythm
      measured at the beginning of the MSLT could be used to detect SDB patients with
      and without EDS before the appearance of sleep onset.

PMID- 25860588
TI  - Laparoscopic right colectomy in patients treated with previous gastrectomy.
AB  - PURPOSE: Laparoscopic colorectal surgery is increasingly being performed in
      patients treated with previous abdominal surgery. This is a retrospective study
      designed to evaluate the feasibility of laparoscopic right colectomy in patients
      with a previous history of gastrectomy. METHODS: Of 838 consecutive patients who
      underwent elective laparoscopic right colectomy, 23 had previously undergone
      gastrectomy (PG group) and 516 had no history of previous abdominal surgery (NS
      group). The short-term surgical outcomes were retrospectively investigated in the
      PG and NS groups. RESULTS: The median patient age was 75 years in the PG group
      and 67 years in the NS group (p = 0.0026), and the median body mass index in both
      groups was 19.2 and 22.6 kg/m(2), respectively (p = 0.0006). The mean operative
      time, amount of blood loss and postoperative hospital stay were similar. One
      patient in the PG group and five patients in the NS group required conversion to
      laparotomy (p = 0.1307). Three patients in the PG group experienced postoperative
      complications, one each with an intraperitoneal abscess, wound infection and
      enterocolitis; however, none of these complications were directly attributable to
      adhesiolysis. The rates of intraoperative and postoperative complications were
      similar. CONCLUSIONS: Laparoscopic right colectomy is feasible in patients
      treated with previous gastrectomy.

PMID- 25860589
TI  - Searching for predictors of surgical complications in critically ill surgery
      patients in the intensive care unit: a review.
AB  - We reviewed the use of the levels of C-reactive protein, lactate and
      procalcitonin and/or the Sequential Organ Failure Assessment score to determine
      their diagnostic accuracy for predicting surgical complications in critically ill
      general post-surgery patients. Included were all studies published in PubMed from
      inception to July 2013 that met the following inclusion criteria: evaluation of
      the above parameters, describing their diagnostic accuracy and the risk
      stratification for surgical complications in surgical patients admitted to an
      intensive care unit. No difference in the Sequential Organ Failure Assessment
      scores was seen between patients with or without complications. The D-lactate
      levels were significantly higher in those who developed colonic ischemic
      complications after a ruptured abdominal aortic aneurysm. After gastro-intestinal
      surgery, contradictory data were reported, with both positive and negative use of
      C-reactive protein and procalcitonin in the diagnosis of septic complications.
      However, in trauma patients, the C-reactive protein levels may help to
      discriminate between those with and without infectious causes. We conclude that
      the Sequential Organ Failure Assessment score, lactate concentration and C
      reactive protein level have no significant predictive value for early
      postoperative complications in critically ill post-surgery patients. However,
      procalcitonin seems to be a useful parameter for diagnosing complications in
      specific patient populations after surgery and/or after trauma. 

PMID- 25860590
TI  - Introduction of 2-octyl cyanoacrylate (Dermabond(r)) for incisional hernia mesh
      repair.
AB  - PURPOSE: We developed a new technique, sutureless mesh fixation, using 2-octyl
      cyanoacrylate (Dermabond(r), a surgical tissue adhesive) for incisional hernia
      repair. The objective of this article is to introduce the new technique and to
      examine whether the technique provides sufficient resistance to abdominal
      pressure. METHODS: We conducted two tests using a porcine model, a traction
      experiment and artificial pneumoperitoneum test. In the traction experiment, the
      adherence properties of Dermabond(r) with mesh and peritoneum were examined using
      a tissue fragment from a pig. In the artificial pneumoperitoneum test, which used
      an incisional hernia porcine model, mesh was implanted on the peritoneum in the
      abdominal cavity with Dermabond(r). It was then determined whether sutureless
      mesh fixation could bear artificial abdominal air pressure. RESULTS: In the
      traction experiment, Dermabond(r), which bonded the mesh to the peritoneum,
      tolerated pressure up to 2.45 * 103 mmHg. In the artificial pneumoperitoneum
      test, the mesh was strongly fastened to the peritoneum by means of only
      Dermabond(r), and there was little air circulation even without closing the wound
      over the mesh. CONCLUSIONS: Sutureless mesh fixation with Dermabond(r) is
      technically feasible and promises to provide sufficient resistance to abdominal
      pressure.

PMID- 25860591
TI  - Limited resections for duodenal gastrointestinal stromal tumors and their
      oncologic outcomes.
AB  - PURPOSE: Limited resection is considered a treatment option for duodenal
      gastrointestinal stromal tumors (GISTs) whenever technically feasible, but the
      optimal technique for this is still not well defined. We present the various
      types of limited resections for duodenal GISTs and analyze their postoperative
      outcomes. METHODS: The subjects of this retrospective clinicopathologic analysis
      were 21 patients who underwent limited resections for duodenal GIST between May,
      2001 and June, 2014. The median follow-up period was 52 months (range 5-125
      months). RESULTS: The patients comprised 12 men and 9 women, with a median age of
      59 years (range 45-75 years), all of whom were treated by various forms of
      limited resection with clear margins. There were ten wedge resections with
      primary closure (eight open/two laparoscopic), two wedge resections with Roux-en
      Y duodenojejunostomy, three segmental duodenectomies with end-to-end
      duodenoduodenostomy, and six segmental duodenectomies with end-to-end
      duodenojejunostomy. Hepatic metastasis was found 27 months after surgery in one
      patient, who was given imatinib mesylate for 17 months to slow disease
      progression. The other 20 patients were alive and recurrence free at the time of
      writing. CONCLUSION: Excellent recurrence-free survival was achieved after
      limited resections, supporting the consideration of various methods of limited
      resection as the treatment of choice for duodenal GISTs.

PMID- 25860593
TI  - Evaluating Landscape Connectivity for Puma concolor and Panthera onca Among
      Atlantic Forest Protected Areas.
AB  - Strictly Protected Areas and riparian forests in Brazil are rarely large enough
      or connected enough to maintain viable populations of carnivores and animal
      movement over time, but these characteristics are fundamental for species
      conservation as they prevent the extinction of isolated animal populations.
      Therefore, the need to maintain connectivity for these species in human-dominated
      Atlantic landscapes is critical. In this study, we evaluated the landscape
      connectivity for large carnivores (cougar and jaguar) among the Strictly
      Protected Areas in the Atlantic Forest, evaluated the efficiency of the Mosaics
      of Protected Areas linked to land uses in promoting landscape connectivity,
      identified the critical habitat connections, and predicted the landscape
      connectivity status under the implementation of legislation for protecting
      riparian forests. The method was based on expert opinion translated into land use
      and land cover maps. The results show that the Protected Areas are still
      connected by a narrow band of landscape that is permeable to both species and
      that the Mosaics of Protected Areas increase the amount of protected area but
      fail to increase the connectivity between the forested mountain ranges (Serra do
      Mar and Serra da Mantiqueira). Riparian forests greatly increase connectivity,
      more than tripling the cougars' priority areas. We note that the selection of
      Brazilian protected areas still fails to create connectivity among the legally
      protected forest remnants. We recommend the immediate protection of the priority
      areas identified that would increase the structural landscape connectivity for
      these large carnivores, especially paths in the SE/NW direction between the two
      mountain ranges. 

PMID- 25860592
TI  - Minimally invasive esophagectomy performed with the patient in a prone position:
      a systematic review.
AB  - PURPOSE: We reviewed the surgical results of minimally invasive esophagectomy for
      esophageal cancer, performed with the patient in a prone position (MIE-PP), to
      assess its benefits. METHODS: A systematic literature search was performed, and
      articles that fully described the surgical results of MIE-PP were selected.
      Parameters such as operative time, blood loss, and postoperative outcomes were
      compared with those obtained for open transthoracic esophagectomy (OE) and
      minimally invasive esophagectomy in a lateral decubitus position (MIE-LP).
      RESULTS: The conversion rate from MIE-PP to open surgery was very low. MIE-PP was
      associated with longer operative time and lower blood loss than OE. Although
      studies from a single institution did not show an apparent difference in
      morbidity or mortality among the three operative groups, results of a multicenter
      randomized controlled trial showed a reduction in pulmonary infection and
      recurrent laryngeal nerve palsy in MIE-PP, compared with OE. The benefits of MIE
      PP vs. those of MIE-LP remain controversial. CONCLUSION: Theoretically, the
      operative results of MIE-PP might be better than those of MIE-LP for patients
      with esophageal cancer; however, studies have not yet verified this. Further
      clinical studies are required to establish whether the advantages of MIE-PP can
      be translated into clinical outcome.

PMID- 25860594
TI  - Contingent Valuation of Residents' Attitudes and Willingness-to-Pay for Non-point
      Source Pollution Control: A Case Study in AL-Prespa, Southeastern Albania.
AB  - Recently, local governments in Albania have begun paying attention to management
      of small watershed, because there are specific boundaries and people living
      within a watershed basin tend to be more concerned about the basin's
      environmental, economic, and social development. But this natural resource
      management and non-point source (NPS) pollution control is still facing
      challenges. Albanian part of Prespa Park (AL-Prespa) is a good case study, as it
      is a protected wetland area of high biodiversity and long human history. In this
      framework, this study was undertaken, the main objectives of which were to
      explore: (1) the attitudes of the residents toward NPS pollution control, (2)
      their willingness-to-pay for improving water quality, and (3) factors affecting
      the residents' willingness-to-pay. Descriptive statistics, one-way ANOVA
      (analysis of variance), Chi-square analysis, and multivariate data analysis
      techniques were used. Findings strongly suggested that the residents' attitudes
      toward NPS pollution control in this area were positive. With the combination of
      two major contingent valuation methods--dichotomous choice and open-ended
      formats, the survey results indicated that the average yearly respondents' WTP
      was <euro>6.4. The survey revealed that residents' yearly income and education
      level were the main factors affecting residents' willingness-to-pay for NPS
      pollution control in this area, and there was no significant correlation between
      residents' yearly income and their education level. The current study would lay a
      solid foundation on decision-making in further NPS pollution control and public
      participation through community-based watershed management policies in AL-Prespa
      watershed and similar areas.

PMID- 25860596
TI  - Assessing the effects of woody plant traits on understory herbaceous cover in a
      semiarid rangeland.
AB  - The ecological impact of woody plant encroachment in rangeland ecosystems has
      traditionally been evaluated based on correlation studies between densities of
      dissimilar woody plants and various ecosystem properties. However, ecosystem
      properties respond differently to woody plant encroachment because of variations
      in adaptation of co-occurring woody plants. The objective of this study is to
      predict the impact of woody plant encroachment on understory herbaceous cover
      based on analysis of key traits of woody plants. We conducted a vegetation survey
      in 4 savanna sites in southwestern Ethiopia and compared 9 different key traits
      of 19 co-occurring woody plants with understory herbaceous cover. Our results
      show that low understory herbaceous cover is associated with evergreen leaf
      phenology, shrubby growth form, smaller relative crown-base height and larger
      relative crown diameter. However, the N2-fixing ability and density of woody
      plants did not influence the understory herbaceous cover. This shows that traits
      of individual woody plants can predict the impact of woody plant encroachment on
      understory herbaceous cover better than density does. The finding improves our
      ability to accurately predict the impact of woody plant encroachment on various
      ecosystem properties in highly diverse savanna systems. This plant trait-based
      approach could be also used as an important management exercise to assess and
      predict the impact of encroaching woody species in several rangeland ecosystems.

PMID- 25860595
TI  - Response to Julian et al. (2015) "comment on and reinterpretation of Gabriel et
      al. (2014) 'fish mercury and surface water sulfate relationships in the
      everglades protection area'".
AB  - The purpose of this forum is to respond to a rebuttal submitted by Julian et al.,
      Environ Manag 55:1-5, 2015 where they outlined their overall disagreement with
      the data preparation, methods, and interpretation of results presented in Gabriel
      et al. (Environ Manag 53:583-593, 2014). Here, we provide background information
      on the research premise presented in Gabriel et al. (Environ Manag 53:583-593,
      2014) and provide a defense for this work using five themes. In spite of what
      Julian et al. perceive as limitations in the sampling methods and analytical
      tools used for this work, the relationships found between fish total mercury and
      surface water sulfate concentrations in Gabriel et al. (Environ Manag 53:583-593,
      2014) are comparable to relationships between pore water methylmercury (MeHg) and
      pore water sulfate found in past studies indicating that sulfate is important to
      MeHg production and bioaccumulation in the Everglades. Julian et al. state
      "...there is no way to justify any ecosystem-wide sulfur strategy as a management
      approach to reduce mercury risk in the (Everglades) as suggested by Gabriel et
      al. (Environ Manag 53:583-593, 2014), Corrales et al. (Sci Tot Environ 409:2156
      2162, 2011) and Orem et al. (Rev Environ Sci Technol 41 (S1):249-288, 2011)." We
      disagree, and having stated why sulfate input reduction to the Everglades may be
      the most effective means of reducing mercury in Everglades fish, it is important
      that research on sulfur and mercury biogeochemistry continues. If further studies
      support the relationship between sulfate loading reduction and MeHg reduction,
      sulfur mass balance studies should commence to (1) better quantify agricultural
      and connate seawater sulfate inputs and (2) define opportunities to reduce
      sulfate inputs to the Everglades ecosystem. 

PMID- 25860597
TI  - A multivariate approach for mapping fire ignition risk: the example of the
      National Park of Cilento (southern Italy).
AB  - Recent advances in fire management led landscape managers to adopt an integrated
      fire fighting strategy in which fire suppression is supported by prevention
      actions and by knowledge of local fire history and ecology. In this framework, an
      accurate evaluation of fire ignition risk and its environmental drivers
      constitutes a basic step toward the optimization of fire management measures. In
      this paper, we propose a multivariate method for identifying and spatially
      portraying fire ignition risk across a complex and heterogeneous landscape such
      as the National Park of Cilento, Vallo di Diano, and Alburni (southern Italy).
      The proposed approach consists first in calculating the fire selectivity of
      several landscape features that are usually related to fire ignition, such as
      land cover or topography. Next, the fire selectivity values of single landscape
      features are combined with multivariate segmentation tools. The resulting fire
      risk map may constitute a valuable tool for optimizing fire prevention strategies
      and for efficiently allocating fire fighting resources. 

PMID- 25860598
TI  - Pinning down randomness.
AB  - While some behavioral responses to a stimulus are invariant in animals, most are
      more likely to be variable or stochastic. In this issue, Gordus et al. illuminate
      a set of combinatorial neuronal activities that control the variability of a
      chemotactic behavior in response to an odor, providing a tractable system for
      understanding how stochastic circuit dynamics affect behavior.

PMID- 25860599
TI  - The clammy grip of parasitic tumors.
AB  - An epidemic of leukemia among bivalve molluscs is spreading along the Atlantic
      coast of North America, with a serious population decline of soft-shelled clams.
      In this issue of Cell, Metzger et al. use forensic DNA markers to demonstrate
      that the leukemia cells have a clonal origin and appear to be transmitted through
      sea water.

PMID- 25860600
TI  - Gut microbiota: the link to your second brain.
AB  - Serotonin is a highly ubiquitous signaling molecule that plays a role in the
      regulation of various physiological functions. Several lines of evidence,
      including the present work from Hsiao and colleagues, demonstrate that, in the
      gut, microbial-derived metabolites affect the production of serotonin that in
      turn impacts host physiological functions. 

PMID- 25860601
TI  - A collective path toward regeneration.
AB  - How do cells collectively control an organ's behavior? By plucking various
      numbers of hairs from the mouse skin, Chen et al. show that hairs regenerate only
      when a sufficiently high density of them are plucked. Remarkably, a hair follicle
      can only regenerate in concert with other follicles, but not autonomously.

PMID- 25860602
TI  - Close encounters of the lysosome-peroxisome kind.
AB  - Lysosomes provide a major source for cellular cholesterol; however, most of this
      cholesterol is trafficked to the plasma membrane via unknown mechanisms. Chu et
      al. identify an unexpected role for peroxisomes in the transport of cholesterol
      from the lysosome to the plasma membrane via a lysosome-peroxisome membrane
      contact site.

PMID- 25860603
TI  - Intracellular bacteria find the right motion.
AB  - Benanti et al. report that Burkholderia pseudomallei and Burkholderia mallei
      bacteria express proteins that mimic Ena/Vasp family proteins to polymerize
      actin, thereby inducing actin-based motility. Thus, bacteria can use the various
      cellular actin polymerization mechanisms for intra- and inter-cellular
      dissemination.

PMID- 25860604
TI  - Immunoengineering: how nanotechnology can enhance cancer immunotherapy.
AB  - Although cancer immunotherapy can lead to durable outcomes, the percentage of
      patients who respond to this disruptive approach remains modest to date.
      Encouragingly, nanotechnology can enhance the efficacy of immunostimulatory small
      molecules and biologics by altering their co-localization, biodistribution, and
      release kinetics. 

PMID- 25860605
TI  - Immune checkpoint targeting in cancer therapy: toward combination strategies with
      curative potential.
AB  - Research in two fronts has enabled the development of therapies that provide
      significant benefit to cancer patients. One area stems from a detailed knowledge
      of mutations that activate or inactivate signaling pathways that drive cancer
      development. This work triggered the development of targeted therapies that lead
      to clinical responses in the majority of patients bearing the targeted mutation,
      although responses are often of limited duration. In the second front are the
      advances in molecular immunology that unveiled the complexity of the mechanisms
      regulating cellular immune responses. These developments led to the successful
      targeting of immune checkpoints to unleash anti-tumor T cell responses, resulting
      in durable long-lasting responses but only in a fraction of patients. In this
      Review, we discuss the evolution of research in these two areas and propose that
      intercrossing them and increasing funding to guide research of combination of
      agents represent a path forward for the development of curative therapies for the
      majority of cancer patients.

PMID- 25860606
TI  - Ubiquitous L1 mosaicism in hippocampal neurons.
AB  - Somatic LINE-1 (L1) retrotransposition during neurogenesis is a potential source
      of genotypic variation among neurons. As a neurogenic niche, the hippocampus
      supports pronounced L1 activity. However, the basal parameters and biological
      impact of L1-driven mosaicism remain unclear. Here, we performed single-cell
      retrotransposon capture sequencing (RC-seq) on individual human hippocampal
      neurons and glia, as well as cortical neurons. An estimated 13.7 somatic L1
      insertions occurred per hippocampal neuron and carried the sequence hallmarks of
      target-primed reverse transcription. Notably, hippocampal neuron L1 insertions
      were specifically enriched in transcribed neuronal stem cell enhancers and
      hippocampus genes, increasing their probability of functional relevance. In
      addition, bias against intronic L1 insertions sense oriented relative to their
      host gene was observed, perhaps indicating moderate selection against this
      configuration in vivo. These experiments demonstrate pervasive L1 mosaicism at
      genomic loci expressed in hippocampal neurons.

PMID- 25860607
TI  - Modeling familial cancer with induced pluripotent stem cells.
AB  - In vitro modeling of human disease has recently become feasible with induced
      pluripotent stem cell (iPSC) technology. Here, we established patient-derived
      iPSCs from a Li-Fraumeni syndrome (LFS) family and investigated the role of
      mutant p53 in the development of osteosarcoma (OS). LFS iPSC-derived osteoblasts
      (OBs) recapitulated OS features including defective osteoblastic differentiation
      as well as tumorigenic ability. Systematic analyses revealed that the expression
      of genes enriched in LFS-derived OBs strongly correlated with decreased time to
      tumor recurrence and poor patient survival. Furthermore, LFS OBs exhibited
      impaired upregulation of the imprinted gene H19 during osteogenesis. Restoration
      of H19 expression in LFS OBs facilitated osteoblastic differentiation and
      repressed tumorigenic potential. By integrating human imprinted gene network
      (IGN) into functional genomic analyses, we found that H19 mediates suppression of
      LFS-associated OS through the IGN component DECORIN (DCN). In summary, these
      findings demonstrate the feasibility of studying inherited human cancer syndromes
      with iPSCs.

PMID- 25860608
TI  - Horizontal transmission of clonal cancer cells causes leukemia in soft-shell
      clams.
AB  - Outbreaks of fatal leukemia-like cancers of marine bivalves throughout the world
      have led to massive population loss. The cause of the disease is unknown. We
      recently identified a retrotransposon, Steamer, that is highly expressed and
      amplified to high copy number in neoplastic cells of soft-shell clams (Mya
      arenaria). Through analysis of Steamer integration sites, mitochondrial DNA
      single-nucleotide polymorphisms (SNPs), and polymorphic microsatellite alleles,
      we show that the genotypes of neoplastic cells do not match those of the host
      animal. Instead, neoplastic cells from dispersed locations in New York, Maine,
      and Prince Edward Island (PEI), Canada, all have nearly identical genotypes that
      differ from those of the host. These results indicate that the cancer is
      spreading between animals in the marine environment as a clonal transmissible
      cell derived from a single original clam. Our findings suggest that horizontal
      transmission of cancer cells is more widespread in nature than previously
      supposed.

PMID- 25860609
TI  - Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis.
AB  - The gastrointestinal (GI) tract contains much of the body's serotonin (5
      hydroxytryptamine, 5-HT), but mechanisms controlling the metabolism of gut
      derived 5-HT remain unclear. Here, we demonstrate that the microbiota plays a
      critical role in regulating host 5-HT. Indigenous spore-forming bacteria (Sp)
      from the mouse and human microbiota promote 5-HT biosynthesis from colonic
      enterochromaffin cells (ECs), which supply 5-HT to the mucosa, lumen, and
      circulating platelets. Importantly, microbiota-dependent effects on gut 5-HT
      significantly impact host physiology, modulating GI motility and platelet
      function. We identify select fecal metabolites that are increased by Sp and that
      elevate 5-HT in chromaffin cell cultures, suggesting direct metabolic signaling
      of gut microbes to ECs. Furthermore, elevating luminal concentrations of
      particular microbial metabolites increases colonic and blood 5-HT in germ-free
      mice. Altogether, these findings demonstrate that Sp are important modulators of
      host 5-HT and further highlight a key role for host-microbiota interactions in
      regulating fundamental 5-HT-related biological processes.

PMID- 25860611
TI  - Cholesterol transport through lysosome-peroxisome membrane contacts.
AB  - Cholesterol is dynamically transported among organelles, which is essential for
      multiple cellular functions. However, the mechanism underlying intracellular
      cholesterol transport has remained largely unknown. We established an
      amphotericin B-based assay enabling a genome-wide shRNA screen for delayed LDL
      cholesterol transport and identified 341 hits with particular enrichment of
      peroxisome genes, suggesting a previously unappreciated pathway for cholesterol
      transport. We show dynamic membrane contacts between peroxisome and lysosome,
      which are mediated by lysosomal Synaptotagmin VII binding to the lipid PI(4,5)P2
      on peroxisomal membrane. LDL-cholesterol enhances such contacts, and cholesterol
      is transported from lysosome to peroxisome. Disruption of critical peroxisome
      genes leads to cholesterol accumulation in lysosome. Together, these findings
      reveal an unexpected role of peroxisome in intracellular cholesterol transport.
      We further demonstrate massive cholesterol accumulation in human patient cells
      and mouse model of peroxisomal disorders, suggesting a contribution of abnormal
      cholesterol accumulation to these diseases.

PMID- 25860610
TI  - Organ-level quorum sensing directs regeneration in hair stem cell populations.
AB  - Coordinated organ behavior is crucial for an effective response to environmental
      stimuli. By studying regeneration of hair follicles in response to patterned hair
      plucking, we demonstrate that organ-level quorum sensing allows coordinated
      responses to skin injury. Plucking hair at different densities leads to a
      regeneration of up to five times more neighboring, unplucked resting hairs,
      indicating activation of a collective decision-making process. Through data
      modeling, the range of the quorum signal was estimated to be on the order of 1
      mm, greater than expected for a diffusible molecular cue. Molecular and genetic
      analysis uncovered a two-step mechanism, where release of CCL2 from injured hairs
      leads to recruitment of TNF-alpha-secreting macrophages, which accumulate and
      signal to both plucked and unplucked follicles. By coupling immune response with
      regeneration, this mechanism allows skin to respond predictively to distress,
      disregarding mild injury, while meeting stronger injury with full-scale
      cooperative activation of stem cells.

PMID- 25860612
TI  - KPC1-mediated ubiquitination and proteasomal processing of NF-kappaB1 p105 to p50
      restricts tumor growth.
AB  - NF-kappaB is a key transcriptional regulator involved in inflammation and cell
      proliferation, survival, and transformation. Several key steps in its activation
      are mediated by the ubiquitin (Ub) system. One uncharacterized step is limited
      proteasomal processing of the NF-kappaB1 precursor p105 to the p50 active
      subunit. Here, we identify KPC1 as the Ub ligase (E3) that binds to the ankyrin
      repeats domain of p105, ubiquitinates it, and mediates its processing both under
      basal conditions and following signaling. Overexpression of KPC1 inhibits tumor
      growth likely mediated via excessive generation of p50. Also, overabundance of
      p50 downregulates p65, suggesting that a p50-p50 homodimer may modulate
      transcription in place of the tumorigenic p50-p65. Transcript analysis reveals
      increased expression of genes associated with tumor-suppressive signals. Overall,
      KPC1 regulation of NF-kappaB1 processing appears to constitute an important
      balancing step among the stimulatory and inhibitory activities of the
      transcription factor in cell growth control.

PMID- 25860614
TI  - SnapShot: Origins of DNA replication.
AB  - The fundamental unit of DNA replication, the replicon, is governed by a cis
      acting replicator sequence and a trans-activating initiator factor. Despite the
      increased size and complexity of eukaryotic genomes, eukaryotic DNA replication
      continues to be guided by the fundamental principles and concepts established in
      the replicon model. 

PMID- 25860613
TI  - Virulent Burkholderia species mimic host actin polymerases to drive actin-based
      motility.
AB  - Burkholderia pseudomallei and B. mallei are bacterial pathogens that cause
      melioidosis and glanders, whereas their close relative B. thailandensis is non
      pathogenic. All use the trimeric autotransporter BimA to facilitate actin-based
      motility, host cell fusion, and dissemination. Here, we show that BimA orthologs
      mimic different host actin-polymerizing proteins. B. thailandensis BimA activates
      the host Arp2/3 complex. In contrast, B. pseudomallei and B. mallei BimA mimic
      host Ena/VASP actin polymerases in their ability to nucleate, elongate, and
      bundle filaments by associating with barbed ends, as well as in their use of WH2
      motifs and oligomerization for activity. Mechanistic differences among BimA
      orthologs resulted in distinct actin filament organization and motility
      parameters, which affected the efficiency of cell fusion during infection. Our
      results identify bacterial Ena/VASP mimics and reveal that pathogens imitate the
      full spectrum of host actin-polymerizing pathways, suggesting that mimicry of
      different polymerization mechanisms influences key parameters of infection.

PMID- 25860615
TI  - Respiratory motion estimation in x-ray angiography for improved guidance during
      coronary interventions.
AB  - During percutaneous coronary interventions (PCI) catheters and arteries are
      visualized by x-ray angiography (XA) sequences, using brief contrast injections
      to show the coronary arteries. If we could continue visualizing the coronary
      arteries after the contrast agent passed (thus in non-contrast XA frames), we
      could potentially lower contrast use, which is advantageous due to the toxicity
      of the contrast agent. This paper explores the possibility of such visualization
      in mono-plane XA acquisitions with a special focus on respiratory based coronary
      artery motion estimation. We use the patient specific coronary artery centerlines
      from pre-interventional 3D CTA images to project on the XA sequence for artery
      visualization. To achieve this, a framework for registering the 3D centerlines
      with the mono-plane 2D + time XA sequences is presented. During the registration
      the patient specific cardiac and respiratory motion is learned. We investigate
      several respiratory motion estimation strategies with respect to accuracy,
      plausibility and ease of use for motion prediction in XA frames with and without
      contrast. The investigated strategies include diaphragm motion based prediction,
      and respiratory motion extraction from the guiding catheter tip motion. We
      furthermore compare translational and rigid respiratory based heart motion. We
      validated the accuracy of the 2D/3D registration and the respiratory and cardiac
      motion estimations on XA sequences of 12 interventions. The diaphragm based
      motion model and the catheter tip derived motion achieved 1.58 mm and 1.83 mm
      median 2D accuracy, respectively. On a subset of four interventions we evaluated
      the artery visualization accuracy for non-contrast cases. Both diaphragm, and
      catheter tip based prediction performed similarly, with about half of the cases
      providing satisfactory accuracy (median error < 2 mm).

PMID- 25860616
TI  - (90)Y-PET/CT Imaging Quantification for Dosimetry in Peptide Receptor
      Radionuclide Therapy: Analysis and Corrections of the Impairing Factors.
AB  - PURPOSE: We evaluated the possibility to assess (90)Y-PET/CT imaging
      quantification for dosimetry in (90)Y-peptide receptor radionuclide therapy.
      METHODS: Tests were performed by Discovery 710 Elite (GE) PET/CT equipment. A
      body-phantom containing radioactive-coplanar-spheres was filled with (90)Y water
      solution to reproduce different signal-to-background-activity-ratios (S/N). We
      studied minimum detectable activity (MDA) concentration, contrast-to-noise ratio
      (CNR), and full-width-at-half-maximum (FWHM). Subsequently, three recovery
      coefficients (RC)-based correction approaches were evaluated: maximum-RC,
      resolution-RC, and isovolume-RC. The analysis of the volume segmentation
      thresholding method was also assessed to derive a relationship between the true
      volume of the targets and the threshold to be applied to the PET images. (90)Y
      PET/CT imaging quantification was then achieved on some patients and related with
      preclinical tests. Moreover, the dosimetric evaluation was obtained on the target
      regions. RESULTS: CNR value was greater than 5 if the MDA was greater than 0.2
      MBq/mL with no background activity and 0.5-0.7 MBq/mL with S/N ranging from 3 to
      6. FWHM was equal to 7 mm. An exponential fitting of isovolume RCs-based
      correction technique was adopted for activity quantification. Adaptive
      segmentation thresholding exponential curves were obtained and applied for target
      volume identification in three signal-to-background-activity-ratios. The imaging
      quantification study and dosimetric evaluations in clinical cases was feasible
      and the results were coherent with those obtained in preclinical tests.
      CONCLUSIONS: (90)Y-PET/CT imaging quantification is possible both in phantoms and
      in patients. Absorbed dose evaluations in clinical applications are strongly
      related to targets activity concentration.

PMID- 25860617
TI  - Characterization of tetratricopeptide repeat-containing proteins critical for
      cilia formation and function.
AB  - Cilia formation and function require a special set of trafficking machinery
      termed intraflagellar transport (IFT), consisting mainly of protein complexes IFT
      A, IFT-B, BBSome, and microtubule-dependent molecular motors. Tetratricopeptide
      repeat-containing (TTC) proteins are widely involved in protein complex
      formation. Nine of them are known to serve as components of the IFT or BBSome
      complexes. How many TTC proteins are cilia-related and how they function,
      however, remain unclear. Here we show that twenty TTC genes were upregulated by
      at least 2-fold during the differentiation of cultured mouse tracheal epithelial
      cells (MTECs) into multiciliated cells. Our systematic screen in zebrafish
      identified four novel TTC genes, ttc4, -9c, -36, and -39c, that are critical for
      cilia formation and motility. Accordingly, their zebrafish morphants displayed
      typical ciliopathy-related phenotypes, including curved body, abnormal otolith,
      hydrocephalus, and defective left-right patterning. The morphants of ttc4 and
      ttc25, a known cilia-related gene, additionally showed pronephric cyst formation.
      Immunoprecipitation indicated associations of TTC4, -9c, -25, -36, and -39c with
      components or entire complexes of IFT-A, IFT-B, or BBSome, implying their
      participations in IFT or IFT-related activities. Our results provide a global
      view for the relationship between TTC proteins and cilia. 

PMID- 25860619
TI  - Tunable luminescence of bithiophene-based flexible Lewis pairs.
AB  - Bithiophene-based flexible Lewis pairs with P(O)R2 (R = phenyl, isopropyl) and
      BMes2 (Mes = 2,4,6-trimethylphenyl) functionalities are able to toggle between
      closed, Lewis adduct and open, unbound Lewis pair structures. The open structure
      is favored in strong hydrogen bond donating solvents or at higher temperatures
      giving rise to an intense charge-transfer (CT) luminescence, while the closed
      structure without this emission dominates in non-hydrogen bond donating solvents
      or at lower temperatures. Intermediate solvents result in an equilibrium mixture
      of both structures, which shows unusual mixed emission that is dependent on
      excitation wavelength. 

PMID- 25860618
TI  - Prospective study of the safety and efficacy of a pancreatic cancer stem cell
      vaccine.
AB  - INTRODUCTION: In this trial, we isolated and cultured pancreatic cancer stem
      cells (CSCs) to produce a vaccine and prospectively evaluated its safety and
      efficacy in low-, medium-, and high-dose groups. MATERIAL AND METHODS: Between
      February and October 2014, we enrolled 90 patients who met the enrollment
      criteria and assigned them to three groups (n = 30). CSC-specific and CSC-non
      specific immunity pre- and post-vaccination were compared by Dunnett's multiple
      comparison test (one-way ANOVA). The data are presented as the mean+/-standard
      deviation. Local and systemic adverse events were recorded in the nursing records
      and compared using the Chi-square test. All statistical analyses were conducted
      using GraphPad software (GraphPad, San Diego, CA, USA). RESULTS: Throughout the
      trial, an injection site reaction was the most common reaction (54 %), and fever
      was least common (9 %). The incidence of these side effects did not vary among
      the three groups. When the pre- and post-vaccination immunity was compared, we
      found that both CSC-nonspecific and CSC-specific responses were significantly
      increased in the high-dose group. CONCLUSION: This study is the first clinical
      trial of a pancreatic CSC vaccine and preliminarily proves its safety and
      efficacy.

PMID- 25860621
TI  - Prediction of Drug-Induced Liver Injury in HepG2 Cells Cultured with Human Liver
      Microsomes.
AB  - Drug-induced liver injury (DILI) via metabolic activation by drug-metabolizing
      enzymes, especially cytochrome P450 (CYP), is a major cause of drug failure and
      drug withdrawal. In this study, an in vitro model using HepG2 cells in
      combination with human liver microsomes was developed for the prediction of DILI.
      The cytotoxicity of cyclophosphamide, a model drug for bioactivation, was
      augmented in HepG2 cells cultured with microsomes in a manner dependent on
      exposure time, microsomal protein concentration, and NADPH. Experiments using pan
      or isoform-selective CYP inhibitors showed that CYP2B6 and CYP3A4 are
      responsible for the bioactivation of cyclophosphamide. In a metabolite
      identification study employing LC-ESI-QTrap and LC-ESI-QTOF, cyclophosphamide
      metabolites including phosphoramide mustard, a toxic metabolite, were detected in
      HepG2 cells cultured with microsomes, but not without microsomes. The cytotoxic
      effects of acetaminophen and diclofenac were also potentiated by microsomes. The
      potentiation of acetaminophen cytotoxicity was dependent on CYP-dependent
      metabolism, and the augmentation of diclofenac cytotoxicity was not mediated by
      either CYP- or UDP-glucuronosyltransferase-dependent metabolism. The cytotoxic
      effects of leflunomide, nefazodone, and bakuchiol were attenuated by microsomes.
      The detoxication of leflunomide by microsomes was attributed to mainly CYP3A4
      dependent metabolism. The protective effect of microsomes against nefazodone
      cytotoxicity was dependent on both CYP-mediated metabolism and nonspecific
      protein binding. Nonspecific protein binding but not CYP-dependent metabolism
      played a critical role in the attenuation of bakuchiol cytotoxicity. The present
      study suggests that HepG2 cells cultured with human liver microsomes can be a
      reliable model in which to predict DILI via bioactivation by drug metabolizing
      enzymes. 

PMID- 25860622
TI  - Iron-Catalyzed Oxidative C-H/C-H Cross-Coupling between Electron-Rich Arenes and
      Alkenes.
AB  - A novel oxidative C-H/C-H cross-coupling reaction between electron-rich arenes
      and alkenes is established utilizing FeCl3 as the catalyst and DDQ as the
      oxidant. Interestingly, direct arylation products are obtained with diaryl
      ethylenes and double arylation products are obtained with styrene derivatives,
      which show high chemoselectivity and good substrate scope. A radical trapping
      experiment and EPR (electron paramagnetic resonance) experiments indicate that
      this reaction proceeds through a radical pathway in which DDQ plays a key role in
      the aryl radical formation. XAFS (X-ray absorption fine structure) experiments
      reveal that the oxidation state of the iron catalyst does not change during the
      reaction, suggesting that FeCl3 might be used as a Lewis acid. Finally, a
      detailed mechanism is proposed for this transformation. 

PMID- 25860620
TI  - The chemopotential effect of Annona muricata leaves against azoxymethane-induced
      colonic aberrant crypt foci in rats and the apoptotic effect of Acetogenin
      Annomuricin E in HT-29 cells: a bioassay-guided approach.
AB  - Annona muricata has been used in folk medicine for the treatment of cancer and
      tumors. This study evaluated the chemopreventive properties of an ethyl acetate
      extract of A. muricata leaves (EEAML) on azoxymethane-induced colonic aberrant
      crypt foci (ACF) in rats. Moreover, the cytotoxic compound of EEAML (Annomuricin
      E) was isolated, and its apoptosis-inducing effect was investigated against HT-29
      colon cancer cell line using a bioassay-guided approach. This experiment was
      performed on five groups of rats: negative control, cancer control, EEAML (250
      mg/kg), EEAML (500 mg/kg) and positive control (5-fluorouracil). Methylene blue
      staining of colorectal specimens showed that application of EEAML at both doses
      significantly reduced the colonic ACF formation compared with the cancer control
      group. Immunohistochemistry analysis showed the down-regulation of PCNA and Bcl-2
      proteins and the up-regulation of Bax protein after administration of EEAML
      compared with the cancer control group. In addition, an increase in the levels of
      enzymatic antioxidants and a decrease in the malondialdehyde level of the colon
      tissue homogenates were observed, suggesting the suppression of lipid
      peroxidation. Annomuricin E inhibited the growth of HT-29 cells with an IC50
      value of 1.62 +/- 0.24 MUg/ml after 48 h. The cytotoxic effect of annomuricin E
      was further substantiated by G1 cell cycle arrest and early apoptosis induction
      in HT-29 cells. Annomuricin E triggered mitochondria-initiated events, including
      the dissipation of the mitochondrial membrane potential and the leakage of
      cytochrome c from the mitochondria. Prior to these events, annomuricin E
      activated caspase 3/7 and caspase 9. Upstream, annomuricin E induced a time
      dependent upregulation of Bax and downregulation of Bcl-2 at the mRNA and protein
      levels. In conclusion, these findings substantiate the usage of A. muricata
      leaves in ethnomedicine against cancer and highlight annomuricin E as one of the
      contributing compounds in the anticancer activity of A. muricata leaves. 

PMID- 25860623
TI  - A comparative study of coagulation, granular- and powdered-activated carbon for
      the removal of perfluorooctane sulfonate and perfluorooctanoate in drinking water
      treatment.
AB  - Perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) are persistent
      organic pollutants in the environment and their occurrence causes toxicological
      effects on humans. We examined different conventional coagulant treatments such
      as alum, ferric chloride and polyaluminium chloride in removing these compounds.
      These were then compared with a natural coagulant (Moringa oleifera). We also
      investigated the powdered-activated carbon (PAC) and granular-activated carbon
      (GAC) for removing these compounds. At an initial dose of 5 mg/L, polyaluminium
      chloride led to a higher reduction of PFOS/PFOA compared with alum which in turn
      was higher than ferric. The removal efficiency increased with the increase in
      coagulant dose and decrease in pH. M. oleifera was very effective in reducing
      PFOS and PFOA than conventional coagulants, with a reduction efficiencies of 65%
      and 72%, respectively, at a dose of 30 mg/L. Both PAC and GAC were very effective
      in reducing these compounds than coagulations. PAC led to a higher reduction in
      PFOS and PFOA than GAC due to its greater surface area and shorter internal
      diffusion distances. The addition of PAC (10 min contact time) with coagulation
      (at 5 mg/L dosage) significantly increased the removal efficiency, and the
      maximum removal efficiency was for M. oleifera with 98% and 94% for PFOS and
      PFOA, respectively. The reduction efficiency of PFOS/PFOA was reduced with the
      increase in dissolved organic concentration due to the adsorption competition
      between organic molecules and PFOS/PFOA.

PMID- 25860625
TI  - Personal coping strategies for managing the side effects of antiretroviral
      therapy among patients at an HIV/AIDS clinic in Uganda.
AB  - The side effects of antiretroviral (ARV) medications negatively impact patients'
      quality of life and adherence to treatment. This study describes the burden of
      side effects from ARV treatment as experienced by a sample of HIV/AIDS patients
      and identifies the personal strategies they used to cope with the side effects. A
      total of 166 participants were recruited from a non-governmental HIV/AIDS clinic
      in Entebbe, Uganda. Most of the participants (76%) were females and the mean age
      of the sample was 38 years. Although the participants had taken ARV medications
      for an average period of nine months, a large proportion (76%) could not name the
      medications they were taking. The mean side-effects burden for the participants
      was five side effects. The most common adverse effects reported were tiredness,
      nightmares, mood swings, nausea, poor appetite, insomnia, vomiting and dizziness.
      The main strategies the patients used for coping with the side effects were those
      categorised under information-seeking, social-support seeking and positive
      emotion-focused coping. However, 27% of the participants reported non-adherence
      to their ARV medications as a strategy to cope with the side effects. The
      findings show a significant relationship between the side-effects burden and a
      patient's age (r = 0.530, p <= 0.01) and level of education (r = 0.394, p <=
      0.01). The findings indicate that in the short term after initiating ARV
      treatment most patients are able to cope with the high burden of side effects
      through appropriate strategies, but a sizable portion will fail to cope
      appropriately and thus resort to non-adherence. Clinicians should assist patients
      with continuous health education and counselling that focuses on appropriate
      strategies to cope with the side effects of ARVs in order to buffer the negative
      impact of HIV treatment on patients' adherence and quality of life. 

PMID- 25860626
TI  - Developing visual images for communicating information aboutantiretroviral side
      effects to a low-literate population.
AB  - The side effects of antiretroviral (ARV) therapy are linked to altered quality of
      life and adherence. Poor adherence has also been associated with low health
      literacy skills, with an uninformed patient more likely to make ARV-related
      decisions that compromise the efficacy of the treatment. Low literacy skills
      disempower patients in interactions with healthcare providers and preclude the
      use of existing written patient information materials, which are generally
      written at a high reading level. Visual images or pictograms used as a
      counselling tool or included in patient information leaflets have been shown to
      improve patients' knowledge, particularly in low-literate groups. The objective
      of this study was to design visuals or pictograms illustrating various ARV side
      effects and to evaluate them in a low-literate South African Xhosa population.
      Core images were generated either from a design workshop or from posed photos or
      images from textbooks. The research team worked closely with a graphic artist.
      Initial versions of the images were discussed and assessed in group discussions,
      and then modified and eventually evaluated quantitatively in individual
      interviews with 40 participants who each had a maximum of 10 years of schooling.
      The familiarity of the human body, its facial expressions, postures and actions
      contextualised the information and contributed to the participants'
      understanding. Visuals that were simple, had a clear central focus and reflected
      familiar body experiences (e.g. vomiting) were highly successful. The
      introduction of abstract elements (e.g. fever) and metaphorical images (e.g.
      nightmares) presented problems for interpretation, particularly to those with the
      lowest educational levels. We recommend that such visual images should be
      designed in collaboration with the target population and a graphic artist, taking
      cognisance of the audience's literacy skills and culture, and should employ a
      multistage iterative process of modification and evaluation. 

PMID- 25860624
TI  - The Relationship Between Insertion Angles, Default Frequency Allocations, and
      Spiral Ganglion Place Pitch in Cochlear Implants.
AB  - OBJECTIVES: Commercially available cochlear implant systems attempt to deliver
      frequency information going down to a few hundred Hertz, but the electrode arrays
      are not designed to reach the most apical regions of the cochlea, which
      correspond to these low frequencies. This may cause a mismatch between the
      frequencies presented by a cochlear implant electrode array and the frequencies
      represented at the corresponding location in a normal-hearing cochlea. In the
      following study, the mismatch between the frequency presented at a given cochlear
      angle and the frequency expected by an acoustic hearing ear at the corresponding
      angle is examined for the cochlear implant systems that are most commonly used in
      the United States. DESIGN: The angular insertion of each of the electrodes on
      four different electrode arrays (MED-EL Standard, MED-EL Flex28, Advanced Bionics
      HiFocus 1J, and Cochlear Contour Advance) was estimated from X-ray. For the
      angular location of each electrode on each electrode array, the predicted spiral
      ganglion frequency was estimated. The predicted spiral ganglion frequency was
      compared with the center frequency provided by the corresponding electrode using
      the manufacturer's default frequency-to-electrode allocation. RESULTS:
      Differences across devices were observed for the place of stimulation for
      frequencies below 650 Hz. Longer electrode arrays (i.e., the MED-EL Standard and
      Flex28) demonstrated smaller deviations from the spiral ganglion map than the
      other electrode arrays. For insertion angles up to approximately 270 degrees ,
      the frequencies presented at a given location were typically approximately an
      octave below what would be expected by a spiral ganglion frequency map, while the
      deviations were larger for angles deeper than 270 degrees . For frequencies above
      650 Hz, the frequency to angle relationship was consistent across all four
      electrode models. CONCLUSIONS: A mismatch was observed between the predicted
      frequency and the default frequency provided by every electrode on all electrode
      arrays. The mismatch can be reduced by changing the default frequency
      allocations, inserting electrodes deeper into the cochlea, or allowing cochlear
      implant users to adapt to the mismatch. Further studies are required to fully
      assess the clinical significance of the frequency mismatch.

PMID- 25860627
TI  - Factors associated with high media coverage of the HIV epidemic in Lesotho.
AB  - Regional studies show that Lesotho outperforms other countries in southern Africa
      in terms of awarding coverage to HIV and AIDS. Through qualitative interviews,
      this study examines the motivations, experiences, and perceived challenges among
      media workers, which could explain the high coverage. While a high level of
      personal commitment seems to be the outcome of interrelated factors-such as media
      workers' personal experience of the country's high HIV prevalence and high
      mortality rate-Lesotho's political leadership and various government initiatives,
      notably the unique 'Know Your Status' campaign, were singled out as a key factor
      behind the high coverage. Moreover, journalists and editors are often consciously
      exploiting the mass media's potential agenda-setting function in order to raise
      attention to HIV and AIDS. Although covering the HIV epidemic has become
      significantly easier in Lesotho because of government efforts, government and
      public officials are simultaneously identified as the main obstacle to more
      comprehensive coverage. 

PMID- 25860629
TI  - The role of law in the regulation of HIV-vaccine research in South Africa and
      Kenya.
AB  - Law is an important regulatory mechanism, particularly for creating an enabling
      research environment. However, the manner in which law addresses issues related
      to medical research, and HIV-vaccine research in particular, is at times
      inadequate and of great concern to the stakeholders involved in such research.
      The challenges for law as a regulatory mechanism in this regard are twofold: the
      complexity of issues related to HIV-vaccine research, and the apparent
      disconnection between the legal and ethical frameworks that are applied in the
      regulation of these issues. This article analyses the extent to which these
      challenges have been addressed in South Africa and Kenya. Especially, it
      highlights the lessons that can be drawn from the two countries in establishing a
      suitable ethical-legal framework for HIV-vaccine research. 

PMID- 25860628
TI  - Treatment adherence following national antiretroviral rollout in South Africa.
AB  - The national antiretroviral (ARV) programme in South Africa commenced in 2004.
      ARV drugs became readily available to all South Africans due to the concerted
      efforts of 'access to all' campaigns. This study investigates medication
      adherence among a sample of South Africans after the ARV rollout in order to gain
      insight into the adherence challenges they face. A semi-structured questionnaire
      was completed by 439 participants from across the country. The results show that
      only 40% of the respondents were able to reach the optimum adherence level of 90%
      or above. The patients who displayed below-optimum adherence often had not been
      part of an ARV-preparation programme, did not have HIV-treatment supporters,
      lacked general knowledge about drug adherence, and felt unsupported by healthcare
      providers in their day-to-day effort to adhere to their medications. They often
      had no money for food or transportation, ran out of ARVs for various reasons,
      suffered from HIV-treatment fatigue, battled with depression, abused alcohol,
      could not disclose to sexual partners that they were on ARVs, and often had to
      hide or skip ARV dosages because they feared stigma and discrimination.
      Suggestions to assist patients to adhere to their ARV medications are made. 

PMID- 25860630
TI  - Cultural obstacles to the rollout of antiretrovirals: an exploratorycross-country
      analysis.
AB  - This article begins with an econometric analysis of potential socioeconomic
      determinants of highly active antiretroviral treatment (HAART) coverage. It shows
      that 'cultural' factors such as language diversity pose challenges to HAART
      coverage, but that the most important drivers of HAART coverage are: region
      (notably, living in the hyper-epidemic region of southern Africa) and access to
      government and donor funding. These economic determinants, however, are
      underpinned by a further cultural dimension-namely public and donor attitudes
      towards HIV/AIDS funding. The second part of the article turns to the issue of
      'donor culture.' It describes the sea change in attitudes which underpinned the
      growth in funding for HIV/AIDS and points to the growing backlash against
      HIV/AIDS funding in which claims are being made that HIV/AIDS has received a
      greater share of funding than warranted by its contribution to the overall
      disease burden, and that Africans themselves would prefer HIV/AIDS resources to
      be allocated to other development objectives. The article argues that neither
      assertion is supported by the available evidence and that opinion data from the
      Afrobarometer surveys suggest that high levels of support exist within Africa for
      continued spending on health and HIV/AIDS, even in the presence of other
      challenges. 

PMID- 25860631
TI  - Nutrition education and counselling as strategic interventions to improvehealth
      outcomes in adult outpatients with HIV: a literature review.
AB  - Malnutrition poses a significant risk for people living with HIV and accelerates
      disease progression. This is because adequate nutrition is essential for optimal
      immune function. This article discusses research on the role and use of nutrition
      education or counselling as a strategic intervention to improve health outcomes
      through better health behaviour in adult outpatients with HIV. Ten studies (five
      quantitative and five qualitative) met the inclusion criteria of the literature
      review. The findings of the studies related to the following outcomes of
      nutrition interventions: increases in fat-free and lean body mass; offsetting the
      adverse effects of HIV infection in patients with a low CD4 cell count;
      significant improvement in dietary patterns with resultant greater adherence to
      HIV medications and fewer side effects; and agreement on the importance of
      addressing the nutrition concerns. The article discusses the five prominent
      themes that emerged from the literature review: 1) ethical issues in HIV/AIDS
      research; 2) the role of health and culture in nutrition interventions; 3) HIV
      stigma and its impact on nutrition interventions; 4) the socioeconomics of HIV
      and AIDS; and 5) food security and emotional wellbeing among persons with HIV.
      Although the evidence base is limited and raises questions about key aspects of
      the quality of the research conducted to date, the overall results show that
      providing HIV-positive adults with culturally relevant and practical nutrition
      strategies can improve health outcomes, health behaviour and quality of life.
      Current and future nutrition interventions for persons with HIV disease should be
      targeted, sustainable, and rigorously evaluated. There is an urgent need for
      research on this topic in developing countries, particularly African ones, which
      are some of the most affected by HIV. 

PMID- 25860632
TI  - Human-resources strategies for managing HIV/AIDS: the case of the South African
      forestry industry.
AB  - Previous work has focused on HIV prevalence among forestry workers and the impact
      of HIV/AIDS on the sustainability of forest resources. Following a review of work
      examining the impacts of HIV/AIDS on the South African economy, this article
      presents original qualitative research examining the responses of company
      management to the HIV epidemic across a range of enterprises in the South African
      forestry industry, including large companies, contractors and cooperatives. At
      the level of the enterprise, management occupies a critical nexus, at which the
      intersecting requirements of complex government legislation, the wellbeing of
      workers and the demands of the business must be met. The research demonstrates
      that large forestry companies tend to provide only a small fraction of their
      workforces with HIV/AIDS education, prevention or treatment services, as they
      have essentially outsourced the requirement through the use of labour-supply
      contractors who, by and large, provide workers with scant HIV/AIDS-related
      programmes or benefits. Moreover, the extent to which the different types of
      forestry enterprises incorporate the management of HIV/AIDS in the workforce with
      the management of the business is highly variable, and in most instances falls
      short of legislative requirements that have been in place for over a decade. The
      implications of this for the forestry industry in South Africa are acute. 

PMID- 25860633
TI  - African communalism and public health policies: the relevance ofindigenous
      concepts of personal identity to HIV/AIDS policies in Botswana.
AB  - This article explores the possible relevance of African communalism to HIV/AIDS
      policies in Botswana and other parts of sub-Saharan Africa. We examine various
      interpretations of African communalism, which many consider to be the cardinal
      insight of African thought. We suggest several applications of this indigenous
      notion of personhood to HIV prevention in general and to routine HIV-testing
      policies in particular. This analysis demonstrates some of the ethical dilemmas
      and cultural complexities inherent in designing as well as implementing effective
      HIV-prevention programmes that strike a conscientious balance between protecting
      individual freedoms and securing public health. Recovering past traditions (such
      as African conceptions of personal identity) is valuable not only for the purpose
      of self-identification but also for helping us meet the challenges and problems
      of today in Africa. We also suggest that the human-rights-based approach to HIV
      prevention, which strives to protect individuals, is possibly incompatible with
      the socio-ethical ideals espoused by African communalism. We conclude that public
      health programmes in Botswana and other parts of sub-Saharan Africa would be more
      effective if those who designed and implemented them possessed a better
      understanding of indigenous conceptions of personhood or human agency as well as
      existing ethno-medical beliefs and cultural practices. 

PMID- 25860634
TI  - HIV/AIDS knowledge among adolescent sign-language users in South Africa.
AB  - People with hearing impairment may have difficulty accessing information about
      HIV/AIDS, especially those who use sign language. Because adolescence is
      characterised by sexual maturation, it is important to gauge levels of HIV/ AIDS
      awareness and knowledge in this age group. For this scoping study, we interviewed
      seven adolescent South African Sign Language (SASL) users (aged 15 to 21) who
      were attending a school outside Johannesburg which caters for hearing-impaired
      learners from limited socioeconomic backgrounds. The responses were transcribed
      and themes were clustered to extract the essence of what was conveyed. The
      participants appeared to have basic knowledge about HIV and AIDS (e.g. prevention
      through the use of condoms); however, gaps in their knowledge included
      misperceptions about contracting HIV infection (e.g. through touching people with
      HIV or AIDS, or rejecting a person who was possibly HIV-positive as a preventive
      measure) and confusing HIV disease with other illnesses (e.g. cancer). Overall,
      the adolescents appeared to have insufficient information about HIV transmission
      and did not appear to fully understand the consequences of infection. The
      findings correlate with other research in Africa showing the difficulties
      experienced by people with disabilities, including hearing impairment, in
      accessing HIV/ AIDS information. The article advocates for policymakers to
      include people with hearing impairment, particularly sign language users, in HIV
      prevention programmes. 

PMID- 25860635
TI  - Correction: recurrent evolution of melanism in South American Felids.

PMID- 25860636
TI  - Retrospective Evaluation of Milrinone Pharmacokinetics in Children With Kidney
      Injury.
AB  - OBJECTIVES: Milrinone is an inotropic agent with vasodilating properties used in
      the treatment of ventricular dysfunction. Milrinone is predominantly eliminated
      by the kidneys and accumulates in the setting of acute kidney injury (AKI). The
      purpose of this study was to evaluate milrinone pharmacokinetics in children with
      AKI with or without continuous renal replacement therapy (CRRT). METHODS:
      Retrospective collection of milrinone therapeutic drug monitoring data in
      patients with AKI, including those requiring CRRT, through chart review from
      January 2008 to March 2014. Pharmacokinetic (PK) data were analyzed by Bayesian
      estimation using a pediatric population PK model (MW/Pharm). Clearance estimates
      were allometrically scaled to body weight. RESULTS: Data on 11 patients were
      available for analysis. Three patients required CRRT. Milrinone concentrations
      during continuous infusion varied 30-fold and ranged from 44 to 1343 ng/mL. Of
      the 33 samples obtained in 11 patients, 24 were outside the target range (72.7%),
      with 16 (48.5%) above and 8 (24.2%) below. Patients with AKI had significantly
      lower milrinone clearance (4.72 +/- 2.26 L/h per 70 kg) compared with published
      data in patients without AKI. There was large between-patient variability in
      milrinone clearance (range: 2.91-13.6 L/h per 70 kg). Clearance in patients on
      CRRT ranged from 2.8 to 7.19 L/h per 70 kg. A significant correlation between
      milrinone clearance and estimated creatinine clearance was observed (r = 0.70, P
      = 0.0097). Allometrically scaled milrinone clearance was lower in the youngest
      patients (younger than 2 years), suggestive of ongoing renal maturation and
      existing AKI. CONCLUSIONS: Pediatric patients with AKI have significantly lower
      milrinone clearance compared with published data in patients without AKI. Large
      variability was noted in milrinone concentrations, and they were frequently
      outside the target range. The large between-patient variability in milrinone
      concentrations suggests that dosing regimens should be individualized in this
      population of critically ill patients. Evaluation of PK model-based milrinone
      dose optimization and the use of biomarkers as predictors of changes in clearance
      warrant further study.

PMID- 25860637
TI  - Exertional heat illness: emerging concepts and advances in prehospital care.
AB  - Exertional heat illness is a classification of disease with clinical
      presentations that are not always diagnosed easily. Exertional heat stroke is a
      significant cause of death in competitive sports, and the increasing popularity
      of marathons races and ultra-endurance competitions will make treating many heat
      illnesses more common for Emergency Medical Services (EMS) providers. Although
      evidence is available primarily from case series and healthy volunteer studies,
      the consensus for treating exertional heat illness, coupled with altered mental
      status, is whole body rapid cooling. Cold or ice water immersion remains the most
      effective treatment to achieve this goal. External thermometry is unreliable in
      the context of heat stress and direct internal temperature measurement by rectal
      or esophageal probes must be used when diagnosing heat illness and during
      cooling. With rapid recognition and implementation of effective cooling, most
      patients suffering from exertional heat stroke will recover quickly and can be
      discharged home with instructions to rest and to avoid heat stress and exercise
      for a minimum of 48 hours; although, further research pertaining to return to
      activity is warranted.

PMID- 25860638
TI  - Foot sensation testing in the patient with diabetes: introduction of the quick &
      easy assessment tool.
AB  - INTRODUCTION: Sensory testing of patients with diabetes is an integral part of
      preventing new and recurrent wounds. The Semmes- Weinstein monofilament (SWM)
      test is considered the gold standard to screen for loss of protective sensation;
      however, the authors' experience has shown that it is not only time consuming,
      but is of negligible value for a patient with a diabetic foot ulcer (DFU).
      METHODS: This article discusses the shortfalls with regard to the SWM test and
      reviews other techniques for sensory evaluation. In addition, the Quick & Easy
      system is introduced, which combines sensory assessment with guidance for
      anesthesia requirements during wound debridements or other surgical
      interventions. RESULTS: A scale ranging from grade 2 (normal sensation) to grade
      0 (absent sensation) reflects the patient's responses to wound manipulation,
      palpation of an underlying deformity, and/or evaluation of the difference between
      light touch sensation with the patient's hands compared to the feet. For patients
      with total loss of sensation (grade 0), no anesthesia is needed for surgical
      procedures. If there is diminished sensation (grade 1), surgical intervention can
      be performed following administration of either topical or local anesthesia. For
      patients with normal sensation (grade 2), complete anesthesia of the surgical
      site will be required. A preliminary observation was conducted on 50 patients
      with DFUs using the Quick & Easy system. Anesthetic requirements were accurately
      predicted in all cases without the need to modify the type of anesthesia during
      the procedure. CONCLUSION: The Quick & Easy system serves as a simple sensory
      evaluation for a patient with a DFU and provides valuable anesthesia guidance for
      wound care procedures.

PMID- 25860639
TI  - A cost-effective method for obtaining standard platelet-rich plasma.
AB  - INTRODUCTION: Platelet-rich plasma (PRP) is used in several different areas of
      surgery to enhance natural healing and the regenerative process by delivering
      increased concentrations of autologous platelets. However, there are
      controversies in the literature regarding the potential benefits of PRP, due
      partly to the lack of optimized and standardized preparation protocols. The aim
      of this study was to develop a standardized PRP preparation protocol. MATERIAL
      AND METHODS: Whole blood was drawn from 18 healthy participants. Double
      centrifugation protocol was applied. The blood from each person was divided into
      6 tubes according to second stage centrifugation force applied, varying from 300
      g to 2000 g. Platelet counts and platelet concentration factors were determined
      and the data obtained were submitted to statistical analysis (repeated measures
      ANOVA, Bonferroni, P < 0.05). RESULTS: When compared to whole blood, the mean
      platelet counts increased significantly in all centrifugation groups, and this
      increase is common with centrifugation force increase. While there was no
      significant difference between the 300 g and 500 g groups (P = 0.051), there were
      differences between the 500 g and 750 g groups (P < 0.001), and the 750 g and
      1000 g groups (P < 0.001). The mean platelet counts were not different between
      upper g groups (1000g, 1500g, 2000g, P = 0.114). The platelet concentration
      factor varied from 1.92-fold to 3.76-fold. There were differences between the 500
      g and 750 g groups (P < 0.001), and between the 750 g and 1000 g groups (P <
      0.001). CONCLUSION: The present study indicates it may be possible to get a
      standard platelet concentration by adjusting centrifugation force individually
      according to each baseline value.

PMID- 25860640
TI  - Long-standing nonhealing charcot foot ulcers that fail conservative care: is
      major amputation always the solution?
AB  - Charcot arthropathy represents a potentially devastating complication in patients
      with diabetes; this is most significant when an ulcer and/or infection are
      present. When conservative therapies fail to relieve symptomatology, amputation
      usually represents the next step in the treatment algorithm. However, in
      appropriate patients, reconstructive procedures performed by specially trained
      surgeons may change this paradigm and prevent amputation. The following case
      report and subsequent literature review discusses a patient with a recalcitrant
      ulcer mitigated by severe Charcot foot deformity who underwent surgical
      intervention leading to preservation of the limb. The goal of this manuscript is
      to heighten awareness of this surgical alternative and foster the wound healing
      clinician to seek out surgeons in their communities with the skills and
      experience to perform these limb preservation procedures and potentially
      forestall amputation.    . 

PMID- 25860642
TI  - Solutions for Africa's health workforce crisis through country based research.

PMID- 25860641
TI  - A Novel TBX1 Loss-of-Function Mutation Associated with Congenital Heart Disease.
AB  - Congenital heart disease (CHD) is the most prevalent type of birth defect in
      humans and is the leading non-infectious cause of infant death worldwide. There
      is a growing body of evidence demonstrating that genetic defects play an
      important role in the pathogenesis of CHD. However, CHD is a genetically
      heterogeneous disease and the genetic basis underpinning CHD in an overwhelming
      majority of patients remains unclear. In this study, the coding exons and splice
      junction sites of the TBX1 gene, which encodes a T-box homeodomain transcription
      factor essential for proper cardiovascular morphogenesis, were sequenced in 230
      unrelated children with CHD. The available family members of the index patient
      carrying an identified mutation and 200 unrelated ethnically matched healthy
      individuals used as controls were subsequently genotyped for TBX1. The functional
      effect of the TBX1 mutation was predicted by online program MutationTaster and
      characterized by using a dual-luciferase reporter assay system. As a result, a
      novel heterozygous TBX1 mutation, p.Q277X, was identified in an index patient
      with double outlet right ventricle (DORV) and ventricular septal defect (VSD).
      Genetic analysis of the proband's available relatives showed that the mutation co
      segregated with CHD transmitted in an autosomal dominant pattern with complete
      penetrance. The nonsense mutation, which was absent in 400 control chromosomes,
      altered the amino acid that was completely conserved evolutionarily across
      species and was predicted to be disease-causing by MutationTaster. Biochemical
      analysis revealed that Q277X-mutant TBX1 lost transcriptional activating function
      when compared with its wild-type counterpart. This study firstly associates TBX1
      loss-of-function mutation with enhanced susceptibility to DORV and VSD in humans,
      which provides novel insight into the molecular mechanism underlying CHD and
      suggests potential implications for the development of new preventive and
      therapeutic strategies for CHD. 

PMID- 25860643
TI  - Significantly increased visceral adiposity index in prehypertension.
AB  - BACKGROUND: The prevalence of prehypertension has increased in China, and
      prehypertension frequently progress to hypertension over a short time period;
      both have become public health problems. Therefore, this study was conducted to
      determine the relationship between the Visceral Adiposity Index (VAI) and blood
      pressure (BP) in China. METHODS: A cross-sectional epidemiological survey was
      conducted in China using a stratified random cluster sampling method. Sex
      specific VAI quartile cut-off points were used as follows: 0.88, 1.41, 2.45 in
      males and 0.85, 1.33, 2.22 in females. Prehypertension and hypertension were each
      defined according to The Seventh Report of the Joint National Committee on the
      Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7)
      guidelines. A multivariate logistic analysis was conducted to analyze the
      relationship among VAI, prehypertension and hypertension. RESULTS: The ORs for
      prehypertension and hypertension in the upper quartiles of the VAI were 1.514
      (1.074-2.133), P=0.018 and 1.660 (1.084-2.542), P=0.020, in males, after
      adjusting for age, education, smoking habits, alcohol consumption, physical
      activity, serum creatinine, fasting glucose, and plasma insulin. Following
      further adjustments for the above confounders, chronic kidney disease, and
      diabetes, the ORs for prehypertension and hypertension in the upper quartile of
      the VAI were 1.660 1.533 (1.086-2.165), P=0.015, and 1.743 (1.133-2.680),
      P=0.011, in males. The ORs for prehypertension and hypertension in the upper
      quartile of the VAI were 1.691 (1.223-2.338), P=0.001, and 1.682 (1.162-2.435),
      P=0.006, in females, after adjusting for age, education, smoking habits, alcohol
      consumption, physical activity, serum creatinine, fasting glucose, and plasma
      insulin. Following further adjustments for the above confounders, chronic kidney
      disease, and diabetes, the ORs for prehypertension and hypertension in the upper
      quartile of the VAI were 1.688 (1.220-2.334), P=0.002, and 1.657 (1.141-2.406),
      P=0.008, in females. CONCLUSIONS: A higher VAI was positively associated with
      both prehypertension and hypertension in both males and females. It is both
      essential and urgent that clinicians take steps to control and prevent visceral
      adiposity.

PMID- 25860645
TI  - Mepolizumab treatment in patients with severe eosinophilic asthma.

PMID- 25860644
TI  - Epigenetic mechanisms contribute to the expression of immune related genes in the
      livers of dairy cows fed a high concentrate diet.
AB  - PURPOSE: Epigenetic modifications critically regulate the expression of immune
      related genes in response to inflammatory stimuli. It has been extensively
      reported that a high concentrate (HC) diet can trigger systemic inflammation in
      dairy cows, yet it is unclear whether epigenetic regulation is involved in the
      expression of immune genes in the livers of dairy cows. This study aimed to
      investigate the impact of epigenetic modifications on the expression of immune
      related genes. EXPERIMENTAL DESIGN: In eight mid-lactating cows, we installed a
      rumen cannula and catheters of the portal and hepatic veins. Cows were randomly
      assigned to either the treatment group fed a high concentrate (HC) diet (60%
      concentrate + 40% forage, n = 4) or a control group fed a low concentrate (LC)
      diet (40% concentrate + 60% forage, n = 4). RESULTS: After 10 weeks of feeding,
      the rumen pH was reduced, and levels of lipopolysaccharide (LPS) in the rumen,
      and portal and hepatic veins were notably increased in the HC group compared with
      the LC group. The expression levels of detected immune response-related genes,
      including Toll-like receptor 4 (TLR4), cytokines, chemokines, and acute phase
      proteins, were significantly up-regulated in the livers of cows fed a HC diet.
      Chromatin loosening at the promoter region of four candidate immune-related genes
      (TLR4, LPS-binding protein, haptoglobin, and serum amyloid A3) was elicited, and
      was strongly correlated with enhanced expression of these genes in the HC group.
      Demethylation at the promoter region of all four candidate immune-related genes
      was accompanied by chromatin decompaction. CONCLUSION: After HC diet feeding, LPS
      derived from the digestive tract translocated to the liver via the portal vein,
      enhancing hepatic immune gene expression. The up-regulation of these immune genes
      was mediated by epigenetic mechanisms, which involve chromatin remodeling and DNA
      methylation. Our findings suggest that modulating epigenetic mechanisms could
      provide novel ways to treat systemic inflammatory responses elicited by the
      feeding of a HC diet.

PMID- 25860646
TI  - Zebrafish xenotransplantation as a tool for in vivo cancer study.
AB  - Zebrafish represents a powerful model for cancer research. Particularly, the
      xenotransplantation of human cancer cells into zebrafish has enormous potential
      for further evaluation of cancer progression and drug discovery. Various cancer
      models have been established in adults, juveniles and embryos of zebrafish. This
      xenotransplantation zebrafish model provides a unique opportunity to monitor
      cancer proliferation, tumor angiogenesis, metastasis, self-renewal of cancer stem
      cells, and drug response in real time in vivo. This review summarizes the use of
      zebrafish as a model for cancer xenotransplantation, and highlights its
      advantages and disadvantages. 

PMID- 25860648
TI  - Serum levels of IL-8, IFNgamma, IL-10, and TGF beta and their gene expression
      levels in severe and non-severe cases of dengue virus infection.
AB  - Increased serum and mRNA levels of cytokines in patients with dengue virus (DV)
      infection suggest that cytokines are one of the key factors in the pathogenesis
      of disease caused by this virus. Here, we tested 211 serum and 56 mRNA samples
      from an equal number of dengue cases to determine the levels of interleukin-8 (IL
      8), interferon gamma (IFN-gamma), interleukin-10 (IL-10) and transforming growth
      factor beta (TGF-beta). A total 70 serum and 15 mRNA samples from healthy
      individual were also tested for cytokines and served as controls. Serum and mRNA
      levels of IL-8 were highest in the earlier days of dengue infection. IFNgamma
      levels peaked one or two days before defervescence. Levels of IL-10 and TGF-beta
      were highest later in dengue infection, and TGF-beta levels peaked on the day of
      defervescence. Mean levels of IFNgamma, TGF beta and IL-10 were higher in samples
      from dengue cases, irrespective of severity, than in healthy controls. In
      contrast, the level of IL-8 was significantly higher in samples from severe
      dengue cases and lower in cases of dengue without warning signs than in healthy
      controls. Children (82.2 % of 101 paediatric cases) commonly had severe dengue
      illness. Samples that were positive for anti-DV IgG antibody had higher levels of
      IL-8 and TGF beta. DV-2 infections were associated with severe dengue illness. IL
      8 and IFNgamma levels were higher in the presence of warning signs of severe
      dengue. Levels of IL-8, IL-10 and TGF beta were independently associated with
      disease outcome. These data provide evidence of an association of IL-8, IFNgamma,
      TGF beta and IL-10 levels with the severity of dengue illness. Especially, IL-8
      levels can be used as a predictor of severe DV infection.

PMID- 25860650
TI  - A trialkylphosphine-driven chemical transformation route to Ag- and Bi-based
      chalcogenides.
AB  - From the standpoint of chemistry, the metastable nature of nanocrystals provides
      us plentiful ground for the research of new nanoscale structural transformations.
      Herein, we report a new phenomenon that trialkylphosphine (TAP) can extract the
      Ag(+) and Bi(3+) from their nanostructural chalcogenides and reduce them to the
      zerovalent state. Based on this principle, a trialkylphosphine-driven chemical
      transformation route has been developed for the synthesis of a series of metals
      and metal-sulfide heterostructures with multiple sulfides as the precursors.
      Using this reaction principle, Ag, Bi, Ag-Ni3S2, Ag-ZnS, Ag-AgInS2, Ag-Bi, and Bi
      Cu7S4 nanostructures can be successively synthesized. These Ag- or Bi-based metal
      chalcogenide heteronanostructures with interesting optical properties or
      multifunctionalities could be of special interest for a variety of applications,
      including high-performance catalysis, biological and biomedical sensing,
      photovoltaic devices, and a new generation of optoelectronic devices. 

PMID- 25860651
TI  - Genomic medicine at the heart of diabetes management.
AB  - Individual predisposition to type 2 diabetes is influenced by the combined effect
      of a constellation of genetic variants and a multitude of environmental
      exposures. Identification of the specific genetic variants involved, and the
      mechanisms through which they operate, provides a powerful approach for
      delivering biological insights that can drive translational benefit, one that is
      already widely exploited in the personalised management of monogenic and
      syndromic forms of diabetes. This commentary develops the argument that
      equivalent translational advances for more common forms of diabetes are unlikely
      to result solely from the ability to define more complete individual inventories
      of genetic risk and environmental exposure. They will also require identification
      of complex molecular signatures able to provide integrative, empirical,
      longitudinal readouts of disease progression. These signatures will track causal
      mechanisms and capture an individual's position within a complex spectrum of
      pathophysiological processes, thereby supporting personalised approaches to
      intervention and treatment. This is one of a series of commentaries under the
      banner '50 years forward', giving personal opinions on future perspectives in
      diabetes, to celebrate the 50th anniversary of Diabetologia (1965-2015).

PMID- 25860647
TI  - A novel POLE mutation associated with cancers of colon, pancreas, ovaries and
      small intestine.
AB  - In some families there is an increased risk for colorectal cancer, caused by
      heritable, but often unidentified genetic mutations predisposing to the disease.
      We have identified the likely genetic cause for disease predisposition in a large
      family with high burden of colorectal adenomas and carcinomas, in addition to
      extra-colonic cancers. This family had previously been tested for known cancer
      susceptibility genes, with negative results. Exome sequencing was used to
      identify a novel mutation, c.1373A>T (p.Tyr458Phe), in the gene for DNA
      polymerase epsilon catalytic subunit (POLE). This mutation is located in the
      active site of the exonuclease domain of the enzyme, and affects a residue that
      has previously been shown to be important for exonuclease activity. The first
      predisposing mutation identified in POLE (c.1270C>G, p.Leu424Val) was associated
      with colorectal cancer only, but another mutation with a broader tumour spectrum
      (c.1089C>A, p.Asn363Lys) has recently been reported. In the family described in
      the present study, carriers generally have multiple colorectal adenomas and
      cancer of colon, pancreas, ovaries and small intestine which represents an
      important broadening of the tumour spectrum of POLE mutation carriers. We also
      observe a large phenotypic variation among the POLE mutation carriers in this
      family, most likely explained by modifying variants in other genes. One POLE
      mutation carrier has a novel variant in EXO1 (c.458C>T, p.Ala153Val), which may
      contribute to a more severe phenotype. The findings in this study will have
      important implications for risk assessment and surveillance of POLE mutation
      carriers. 

PMID- 25860653
TI  - Advances in LC-MS/MS analysis of environmental and food samples.

PMID- 25860652
TI  - Age-Related Differences in Speech Rate Perception Do Not Necessarily Entail Age
      Related Differences in Speech Rate Use.
AB  - PURPOSE: A new literature has suggested that speech rate can influence the
      parsing of words quite strongly in speech. The purpose of this study was to
      investigate differences between younger adults and older adults in the use of
      context speech rate in word segmentation, given that older adults perceive timing
      information differently from younger ones. METHOD: Younger (18-25 years) and
      older (55-65 years) adults performed a sentence transcription task for sentences
      that varied in speech rate context (i.e., distal speech rate) and a syntactic cue
      to the presence of a word boundary. RESULTS: There were no differences between
      younger and older adults in their use of the distal speech rate cue to word
      segmentation. CONCLUSIONS: The differences previously documented between younger
      and older adults in their perception of speech rate cues do not necessarily
      translate to older adults' use of those cues. Older adults' difficulties with
      compressed speech may arise from problems broader than just speech rate alone.

PMID- 25860654
TI  - Ultrasound-assisted dynamic extraction coupled with parallel countercurrent
      chromatography for simultaneous extraction, purification, and isolation of
      phytochemicals: application to isoflavones from red clover.
AB  - A novel procedure comprising ultrasonic-assisted dynamic extraction (UADE)
      coupled with two countercurrent-chromatography systems (parallel countercurrent
      chromatography, PCCC) was developed. This technique offers the possibility for
      simultaneous extraction, solvent configuration, purification, and isolation of
      target compounds. This new approach was applied to the fractionation and
      purification of isoflavones from red clover. The two-phase solvent system was
      prepared by automating the equipment. The lower aqueous phase of the two-phase
      solvent system was used as the UADE solution and as the mobile phase for PCCC.
      After the extraction and purification steps, the purified sample was pumped into
      the countercurrent chromatography 1 (CCC1) column for the first isolation step.
      During CCC1 separation, the sample was enriched and purified and then pumped into
      the CCC2 column for the second isolation step. After completion of the first
      cycle of UADE-PCCC steps, the second-cycle experiments were performed. Using this
      sequence, five target compounds, daidzein, prunetin, genistein, irilone, and
      maackiain, with >95.31 % purity were successfully extracted and isolated using
      the two-phase solvent system of n-hexane-ethyl acetate-ethanol-water
      (0.623:1.00:0.99:1.246, v/v). With this instrumental setup, scientific and
      systematic extraction and isolation of natural products was achieved, and this
      technique has great potential for industrial application. Graphical Abstract
      Simplified schematic of instrumental setup of UADE combined with two HSCCC
      instruments. 

PMID- 25860655
TI  - Emerging contaminant determination in water samples by liquid chromatography
      using a monolithic column coupled with a photodiode array detector.
AB  - Concern about the presence of emerging contaminants in the environment has
      increased because biological activity at low concentrations has been observed.
      The difficulty of detecting and quantifying these compounds encourages the
      development of analytical methods with highly sensitive and selective analytical
      procedures. Pharmaceuticals, pesticides, and industrial chemicals are used and
      finally discarded to the environment. This paper provides a rapid and sensitive
      analytical method for the quantification of eight emerging contaminants
      (carbamazepine, carbofuran, bisphenol A, diuron, 17 alpha ethinylestradiol,
      ametryn, carbazole, and triclosan). A two-level full factorial design for
      optimization of chromatographic separation and sample preparation was performed.
      The separation using a monolithic column (Onyx C18) achieved baseline resolution
      for all compounds in 4.6 min. The optimized sample treatment involved a
      preconcentration step by means of solid-phase extraction using HF Bond Elut-C18
      cartridges, achieving an enrichment factor of 2222. Under optimum conditions,
      good linearity was obtained with a correlation coefficient higher than 0.999. The
      limits of detection and quantification for carbamazepine, carbofuran, bisphenol
      A, diuron, 17 alpha ethinylestradiol, ametryn, and carbazole were in the range of
      0.01-208.7 and 0.03-695.7 ng L(-1), respectively, and for triclosan, the limit of
      detection and quantification was 0.67 and 2.25 MUg L(-1), respectively. Precision
      evaluated as relative standard deviations was lower than 15 %. The proposed
      method was found robust. Finally, the method was successfully applied to
      superficial water samples.

PMID- 25860656
TI  - Serum metabolomics study of polycystic ovary syndrome based on UPLC-QTOF-MS
      coupled with a pattern recognition approach.
AB  - Metabolomics has become an important tool in distinguishing changes in metabolic
      pathways and the diagnosis of human disease. Polycystic ovary syndrome (PCOS) is
      a relatively complicated, heterogeneous endocrine disorder. The etiology and
      pathogenesis of PCOS remain uncertain. In this study, based on the platform of
      ultra performance liquid chromatography tandem quadrupole time-of-flight mass
      spectrometry (UPLC-QTOF-MS) and the method of pattern recognition, a
      comprehensive metabolomics approach has been applied to explore the changes in
      metabolic profiling between PCOS patients (n = 20) and controls (n = 15) as well
      as insulin-resistance (IR) PCOS patients (n = 11) and non-IR PCOS subjects (n =
      9) in serum. In total, 36 metabolites were found significantly different between
      PCOS and controls, and 9 metabolites were discovered significantly different
      between IR and non-IR PCOS patients. Significant increases in the levels of
      saturated and unsaturated fatty acids (myristic acid, linoleic acid, 9-/13-HODE,
      etc.), fatty amides (palmitic amide, oleamide), dehydroepiandrosterone sulfate, L
      glutamic acid, azelaic acid, L-glyceric acid, pyroglutamic acid, and decreases in
      the levels of lysophosphatidylethanolamine, lysophosphatidylcholine, uridine, and
      L-carnitine were found in PCOS patients compared with controls. In IR PCOS
      patients, linoleic acid, myristic acid, palmitoleic acid, and vaccenic acid also
      increased significantly compared with non-IR PCOS patients. All these changed
      metabolites showed abnormalities of steroid hormone biosynthesis, amino acids and
      nucleosides metabolism, glutathione metabolism, and lipids and carbohydrates
      metabolism in PCOS patients. The subgroup IR PCOS patients exhibited greater
      metabolic deviations than non-IR PCOS patients. These findings may help yield
      promising insights into the pathogenesis and advance the diagnosis and prevention
      of PCOS. Graphical Abstract Serum metabolomics signature of polycystic ovary
      syndrome.

PMID- 25860657
TI  - Anxiety and insomnia as modifiable risk factors for somatic symptoms in Chinese:
      a general population-based study.
AB  - OBJECTIVE: This study aims at investigating the stressors that increased the risk
      of somatic symptoms in the general Chinese population. METHODS: Chinese
      participants (n = 202) were recruited in a population-based household survey.
      Somatic symptoms were measured by the Patient Health Questionnaire-15, while
      potential stressors that increased the risk of somatic symptoms were measured by
      the Perceived Stress Scale, Hospital Anxiety and Depression Scale, Insomnia
      Severity Index and ENRICHD Social Support Instrument. RESULTS: Structured
      multiphase regression modeling showed that female gender (estimated coefficient =
      1.47, 95 % CI .7-2.24, p < .001), history of childhood adversities (estimated
      coefficient = .41, 95 % CI .06-.76, p = .023), employed (estimated coefficient =
      .87, 95 % CI .003-1.74, p = .049), a high level of anxiety (estimated coefficient
      = .26, 95 % CI .17-.36, p < .001) and severe insomnia (estimated coefficient =
      .11, 95 % CI .04-.18, p = .003) are significant stressors for increasing the
      risks of somatic symptoms in the Chinese population. CONCLUSION: Physical and
      psychological symptoms are intertwined. It was recommended that reducing anxiety
      and improving sleep quality would be helpful to reduce somatic symptoms. These
      findings help in early identification and treatment of Chinese adults with
      persisting somatization.

PMID- 25860658
TI  - Spontaneous EEG theta/beta ratio and delta-beta coupling in relation to
      attentional network functioning and self-reported attentional control.
AB  - Relationships between electroencephalographic (EEG) slow- and fast-wave frequency
      bands are considered to be of interest in the study of dispositional affective
      traits, emotion regulation, and attentional phenomena. However, to date, no
      previous studies had explored whether both state performance-based and self
      reported attentional control (AC) measures potentially relate to different
      patterns of spontaneous EEG measures, in the absence of emotional stimuli. In the
      present study, individual differences in spontaneous EEG theta/beta ratio and
      delta-beta coupling at frontal and parietal sites were explored in a sample of
      110 healthy volunteers as potential correlates of individual differences in
      performance-based attentional network functioning, as measured through the
      Attentional Network Test for Interactions (ANT-I) and self-reported AC. We found
      that stronger delta-beta coupling at parietal sites was associated with higher
      self-reported AC. However, no significant associations were found between
      executive control network functioning and the EEG ratio or coupling measures.
      Furthermore, a lower spontaneous fronto-parietal theta/beta ratio was found to be
      associated with better orienting network functioning. These results are discussed
      with a focus on the potential utility of spontaneous EEG measures in several
      cortical regions for capturing trait-like individual differences in temperament
      related factors. 

PMID- 25860659
TI  - Orbitofrontal or accumbens dopamine depletion does not affect risk-based decision
      making in rats.
AB  - Considerable evidence has implicated dopamine (DA) signals in target regions of
      midbrain DA neurons such as the medial prefrontal cortex or the core region of
      the nucleus accumbens in controlling risk-based decision-making. However, to date
      little is known about the contribution of DA in the orbitofrontal cortex (OFC)
      and the medial shell region of the nucleus accumbens (AcbS) to risk-based
      decision-making. Here we examined in rats the effects of 6-hydroxydopamine
      induced DA depletions of the OFC and AcbS on risky choice using an instrumental
      two-lever choice task that requires the assessment of fixed within-session reward
      probabilities that were shifted across subsequent sessions, i.e., rats had to
      choose between two levers, a small/certain lever that delivered one certain food
      reward (one pellet at p = 1) and a large/risky lever that delivered a larger
      uncertain food reward with decreasing probabilities across subsequent sessions
      (four pellets at p = 0.75, 0.5, 0.25, 0.125, 0.0625). Results show that systemic
      administration of amphetamine or cocaine increased the preference for the
      large/risky lever. Results further demonstrate that, like sham controls, rats
      with OFC or AcbS DA depletion were sensitive to changes in probabilities for
      obtaining the large/risky reward across sessions and displayed probabilistic
      discounting. These findings point to the view that the basal capacity to evaluate
      the magnitude and likelihood of rewards associated with alternative courses of
      action as well as long-term changes of reward probabilities does not rely on DA
      input to the AcbS or OFC. 

PMID- 25860660
TI  - Pathological findings of saccular cerebral aneurysms-impact of subintimal fibrin
      deposition on aneurysm rupture.
AB  - Although several studies have suggested that aneurysmal wall inflammation and
      laminar thrombus are associated with the rupture of saccular aneurysms, the
      mechanisms leading to the rupture remain obscure. We performed full exposure of
      aneurysms before clip application and attempted to keep the fibrin cap on the
      rupture point. Using these specimens in a nearly original state before surgery,
      we conducted a pathological analysis and studied the differences between ruptured
      and unruptured aneurysms to clarify the mechanism of aneurysmal wall
      degeneration. This study included ruptured (n = 28) and unruptured (n = 12)
      saccular aneurysms resected after clipping. All of the ruptured aneurysms were
      obtained within 24 h of onset. Immunostainings for markers of inflammatory cells
      (CD68) and classical histological staining techniques were performed. Clinical
      variables and pathological findings from ruptured and unruptured aneurysms were
      compared. Patients with ruptured or unruptured aneurysms did not differ by age,
      gender, size, location, and risk factors, such as hypertension, smoking, and
      hyperlipidemia. The absence or fragmentation of the internal elastica lamina, the
      myointimal hyperplasia, and the thinning of the aneurysmal wall were generally
      observed in both aneurysms. The existence of subintimal fibrin deposition,
      organized laminar thrombus, intramural hemorrhage, neovascularization, and
      monocyte infiltration are more frequently observed in ruptured aneurysms.
      Multivariate logistic regression analysis showed that ruptured aneurysm was
      associated with presence of subintimal fibrin deposition and monocyte
      infiltration. These findings suggest that subintimal fibrin deposition and
      chronic inflammation have a strong impact on degeneration of the aneurysmal wall
      leading to their rupture, and this finding may be caused by endothelial
      dysfunction.

PMID- 25860661
TI  - Adoptive T-cell therapy for cancer in the United kingdom: a review of activity
      for the British Society of Gene and Cell Therapy annual meeting 2015.
AB  - Adoptive T-cell therapy is delivering objective clinical responses across a
      number of cancer indications in the early phase clinical setting. Much of this
      clinical activity is taking place at major clinical academic centers across the
      United States. This review focuses upon cancer-focused cell therapy activity
      within the United Kingdom as a contribution to the 2015 British Society of Gene
      and Cell Therapy annual general meeting. This overview reflects the diversity and
      expansion of clinical and preclinical studies within the United Kingdom while
      considering the background context of this work against new infrastructural
      developments and the requirements of nationalized healthcare delivery within the
      UK National Health Service. 

PMID- 25860663
TI  - Splenosis: a rare cause of gastrointestinal bleeding successfully treated with
      transarterial embolization.
AB  - Splenosis, the ectopic implantation of splenic tissue, most commonly occurs in
      the peritoneal cavity following traumatic splenic injury with subsequent
      splenectomy. This entity is asymptomatic in a vast majority of patients. Occult
      gastrointestinal (GI) bleeding is a relatively rare presentation of splenosis.
      Previous cases of splenosis resulting in refractory GI bleeding have been treated
      with surgical excision of the ectopic splenic implant. We report a case of
      splenosis presenting as occult GI bleeding that was eventually treated with
      transarterial embolization. This presents an alternative minimally invasive
      approach to treating a patient with refractory GI bleeding secondary to
      splenosis. 

PMID- 25860664
TI  - Complete rat spinal cord transection as a faithful model of spinal cord injury
      for translational cell transplantation.
AB  - Spinal cord injury (SCI) results in neural loss and consequently motor and
      sensory impairment below the injury. There are currently no effective therapies
      for the treatment of traumatic SCI in humans. Various animal models have been
      developed to mimic human SCI. Widely used animal models of SCI are complete or
      partial transection or experimental contusion and compression, with both bearing
      controversy as to which one more appropriately reproduces the human SCI
      functional consequences. Here we present in details the widely used procedure of
      complete spinal cord transection as a faithful animal model to investigate neural
      and functional repair of the damaged tissue by exogenous human transplanted
      cells. This injury model offers the advantage of complete damage to a spinal cord
      at a defined place and time, is relatively simple to standardize and is highly
      reproducible. 

PMID- 25860662
TI  - The growth and aggressive behavior of human osteosarcoma is regulated by a CaMKII
      controlled autocrine VEGF signaling mechanism.
AB  - Osteosarcoma (OS) is a hyperproliferative malignant tumor that requires a high
      vascular density to maintain its large volume. Vascular Endothelial Growth Factor
      (VEGF) plays a crucial role in angiogenesis and acts as a paracrine and autocrine
      agent affecting both endothelial and tumor cells. The alpha-Ca2+/Calmodulin
      kinase two (alpha-CaMKII) protein is an important regulator of OS growth. Here,
      we investigate the role of alpha-CaMKII-induced VEGF in the growth and
      tumorigenicity of OS. We show that the pharmacologic and genetic inhibition of
      alpha-CaMKII results in decreases in VEGF gene expression (50%) and protein
      secretion (55%), while alpha- CaMKII overexpression increases VEGF gene
      expression (250%) and protein secretion (1,200%). We show that aggressive OS
      cells (143B) express high levels of VEGF receptor 2 (VEGFR-2) and respond to
      exogenous VEGF (100nm) by increasing intracellular calcium (30%). This response
      is ameliorated by the VEGFR inhibitor CBO-P11, suggesting that secreted VEGF
      results in autocrine stimulated alpha-CaMKII activation. Furthermore, we show
      that VEGF and alpha-CaMKII inhibition decreases the transactivation of the HIF
      1alpha and AP-1 reporter constructs. Additionally, chromatin immunoprecipitation
      assay shows significantly decreased binding of HIF-1alpha and AP-1 to their
      responsive elements in the VEGF promoter. These data suggest that alpha-CaMKII
      regulates VEGF transcription by controlling HIF-1alpha and AP-1 transcriptional
      activities. Finally, CBO-P11, KN-93 (CaMKII inhibitor) and combination therapy
      significantly reduced tumor burden in vivo. Our results suggest that VEGF-induced
      OS tumor growth is controlled by CaMKII and dual therapy by CaMKII and VEGF
      inhibitors could be a promising therapy against this devastating adolescent
      disease. 

PMID- 25860665
TI  - Development of Ss-NIE-1 recombinant antigen based assays for immunodiagnosis of
      strongyloidiasis.
AB  - Strongyloides stercoralis is a widely distributed parasite that infects 30 to 100
      million people worldwide. In the United States strongyloidiasis is recognized as
      an important infection in immigrants and refugees. Public health and commercial
      reference laboratories need a simple and reliable method for diagnosis of
      strongyloidiasis to identify and treat cases and to prevent transmission. The
      recognized laboratory test of choice for diagnosis of strongyloidiasis is
      detection of disease specific antibodies, most commonly using a crude parasite
      extract for detection of IgG antibodies. Recently, a luciferase tagged
      recombinant protein of S. stercoralis, Ss-NIE-1, has been used in a luciferase
      immunoprecipitation system (LIPS) to detect IgG and IgG4 specific antibodies. To
      promote wider adoption of immunoassays for strongyloidiasis, we used the Ss-NIE-1
      recombinant antigen without the luciferase tag and developed ELISA and
      fluorescent bead (Luminex) assays to detect S. stercoralis specific IgG4. We
      evaluated the assays using well-characterized sera from persons with or without
      presumed strongyloidiasis. The sensitivity and specificity of Ss-NIE-1 IgG4 ELISA
      were 95% and 93%, respectively. For the IgG4 Luminex assay, the sensitivity and
      specificity were 93% and 95%, respectively. Specific IgG4 antibody decreased
      after treatment in a manner that was similar to the decrease of specific IgG
      measured in the crude IgG ELISA. The sensitivities of the Ss-NIE-1 IgG4 ELISA and
      Luminex assays were comparable to the crude IgG ELISA but with improved
      specificities. However, the Ss-NIE-1 based assays are not dependent on native
      parasite materials and can be performed using widely available laboratory
      equipment. In conclusion, these newly developed Ss-NIE-1 based immunoassays can
      be readily adopted by public health and commercial reference laboratories for
      routine screening and clinical diagnosis of S. stercoralis infection in refugees
      and immigrants in the United States. 

PMID- 25860666
TI  - An improved UPLC-MS/MS platform for quantitative analysis of
      glycerophosphoinositol in mammalian cells.
AB  - The glycerophosphoinositols constitute a class of biologically active lipid
      derived mediators whose intracellular levels are modulated during physiological
      and pathological cell processes. Comprehensive assessment of the role of these
      compounds expands beyond the cellular biology of lipids and includes rapid and
      unambiguous measurement in cells and tissues. Here we describe a sensitive and
      simple liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for
      quantitative analysis of the most abundant among these phosphoinositide
      derivatives in mammalian cells, the glycerophosphoinositol (GroPIns). The method
      has been developed in mouse Raw 264.7 macrophages with limits of quantitation at
      3 ng/ml. Validation on the same cell line showed excellent response in terms of
      linear dynamic range (from 3 to 3,000 ng/ml), intra-day and inter-day precision
      (coefficient of variation <= 7.10%) and accuracy (between 98.1 and 109.0%) in the
      range 10-320 ng/ml. As proof of concept, a simplified analytical platform based
      on this method and external calibration was also tested on four stimulated and
      unstimulated cell lines, including Raw 264.7 macrophages, Jurkat T-cells, A375MM
      melanoma cells and rat basophilic leukemia RBL-2H3 cells. The results indicate a
      wide variation in GroPIns levels among different cell lines and stimulation
      conditions, although the measurements were always in line with the literature. No
      significant matrix effects were observed thus indicating that the here proposed
      method can be of general use for similar determinations in cells of different
      origin. 

PMID- 25860667
TI  - Fast fight detection.
AB  - Action recognition has become a hot topic within computer vision. However, the
      action recognition community has focused mainly on relatively simple actions like
      clapping, walking, jogging, etc. The detection of specific events with direct
      practical use such as fights or in general aggressive behavior has been
      comparatively less studied. Such capability may be extremely useful in some video
      surveillance scenarios like prisons, psychiatric centers or even embedded in
      camera phones. As a consequence, there is growing interest in developing violence
      detection algorithms. Recent work considered the well-known Bag-of-Words
      framework for the specific problem of fight detection. Under this framework,
      spatio-temporal features are extracted from the video sequences and used for
      classification. Despite encouraging results in which high accuracy rates were
      achieved, the computational cost of extracting such features is prohibitive for
      practical applications. This work proposes a novel method to detect violence
      sequences. Features extracted from motion blobs are used to discriminate fight
      and non-fight sequences. Although the method is outperformed in accuracy by state
      of the art, it has a significantly faster computation time thus making it
      amenable for real-time applications. 

PMID- 25860668
TI  - Combinatorial Study of Ag-Te Thin Films and Their Application as Cation Supply
      Layer in CBRAM Cells.
AB  - In this work, we investigate binary Ag-Te thin films and their functionality as a
      cation supply layer in conductive bridge random access memory devices. A
      combinatorial sputter deposition technique is used to deposit a graded Ag(x)Te(1
      x) (0 < x < 1) layer with varying composition as a function of the position on
      the substrate. The crystallinity, surface morphology, and material stability
      under thermal treatment as a function of the composition of the material are
      investigated. From this screening, a narrow composition range between 33 and 38
      at% Te is selected which shows a good morphology and a high melting temperature.
      Functionality of a single Ag(2-delta)Te composition as cation supply layer in
      CBRAM with dedicated Al2O3 switching layer is then investigated by implementing
      it in 580 MUm diameter dot Pt/Ag(2-delta)Te/Al2O3/Si cells. Switching properties
      are investigated and compared to cells with a pure Ag cation supply layer. An
      improved cycling behavior is observed when Te is added compared to pure Ag, which
      we relate to the ionic conducting properties of Ag2Te and the preferred formation
      of Ag-Te phases.

PMID- 25860670
TI  - Correction: Ablation of tumor necrosis factor is associated with decreased
      inflammation and alterations of the microbiota in a mouse model of inflammatory
      bowel disease.

PMID- 25860669
TI  - Engineered self-assembling monolayers for label free detection of influenza
      nucleoprotein.
AB  - Integrating nanotechnology into useable devices requires a combination of bottom
      up and top down methodology. Often the techniques to measure and control these
      different components are entirely different, so methods that can analyse the
      nanoscale component in situ are of increasing importance. Here we describe a
      strategy that employs a self-assembling monolayer of engineered protein chimeras
      to display an array of oriented antibodies (IgG) on a microelectronic device for
      the label free detection of influenza nucleoprotein. The structural and
      functional properties of the bio-interface were characterised by a range of
      physical techniques including surface plasmon resonance, quartz-crystal
      microbalance and neutron reflectometry. This combination of methods reveals a
      13.5 nm thick engineered-monolayer that (i) self-assembles on gold surfaces, (ii)
      captures IgG with high affinity in a defined orientation and (iii) specifically
      recognises the influenza A nucleoprotein. Furthermore we also show that this non
      covalent self-assembled structure can render the dissociation of bound IgG
      irreversible by chemical crosslinking in situ without affecting the IgG function.
      The methods can thus describe in detail the transition from soluble engineered
      molecules with nanometre dimensions to an array that demonstrates the principles
      of a working influenza sensor. 

PMID- 25860672
TI  - [What's new in rectal cancer?].
AB  - BACKGROUND: In recent years, multidisciplinary therapeutic management of rectal
      cancer has evolved. This progress had interest radio and chemotherapy. AIM: To
      describe the main spots of the progress in the therapeutic strategies of the
      disease, surgical techniques and standardization of these techniques,
      particularly regarding locoregional extension in the mesorectum. METHOD:
      Literature review. RESULTS: Treatment of rectal cancer is multidisciplinary. On
      the surgical field, excision of the mesorectum (total mesorectal excision [TME])
      has reduced local recurrence and the genitourinary sequelae. Meanwhile,
      chemoradiotherapy has become important. The standard now is to indicate to T3 T4
      N+ tumors to decrease local recurrence without improving survival, however.
      CONCLUSION: Advances in the management of rectal cancer with both imaging
      progress and therapeutic modalities have improved the prognosis and survival of
      this cancer.

PMID- 25860673
TI  - Predictive factors of Gastrointestinal motility Dysfunction after
      gastrojejunostomy for peptic ulcer stenosis.
AB  - BACKGROUND: Despite the establishment of effective medical therapies in peptic
      ulcer disease, gastric outlet obstruction remains one of the most common health
      problem in Tunisia. Various operations have been attempted, which may lead to
      postoperative morbidity. Gastrointestinal (GI) motility dysfunction is the most
      common complications. AIM: to determine the predictive factor of gastrointestinal
      motility dysfunction after gastrojejunostomy for peptic ulcer stenosis. METHODS:
      We carried out a retrospective study to evaluate the postoperative recovery of
      the motility of the upper gastrointestinal tract after gastrojejunostomy for
      peptic ulcer stenosis. During the 9- year study, 138 patients underwent
      operations for ulcer peptic stenosis. Among the patients, 116 (84,1%) were
      treated with gastrojejunostomy. Descriptive statistics, univariate and
      multivariate analyses were performed. RESULTS: The mean age of patients was 47.85
      years (range: 19- 92years) and most. Were male (84, 5 %). Ninety two (79.3%)
      patients had a documented history of peptic ulcer disease. The duration of
      symptoms ranged from 10 to 372 days (mean: 135.86 days). Eighty two (71%)
      patients were operated on through laparotomy. Laparoscopic procedure was
      performed in 29% of the patients. There was no operative mortality. Perioperative
      morbidity occurred in 12.4% (14 patients). Gastrointestinal motility dysfunction
      occurred in 12 patients (10.3%). It was treated by nasogastric aspiration and
      prokinetics. By univariate analysis; diabetes (0,010), cachexia (0,049), ASA
      class (0.05) were all statistically associated with gastrointestinal motility
      dysfunction in this series. Multivariate logistic regression analysis (table 2)
      showed that the cachexia (0,009), ASA class (0.02) were the main predictors of
      gastrointestinal motility dysfunction after gastrojejunostomy for peptic ulcer
      stenosis in the followed patients. CONCLUSION: Gastrointestinal motility
      dysfunction is the most common complications after gastrojejunostomy for pyloric
      adult stenosis. Surgery must be preceded by careful medical preparation. It is
      more likely to occur in patients with an ASA class 2 or greater. Those patients
      should be considered for other treatment options, such as endoscopic balloon
      dilation.

PMID- 25860671
TI  - Trend and risk factors of diverticulosis in Japan: age, gender, and
      lifestyle/metabolic-related factors may cooperatively affect on the colorectal
      diverticula formation.
AB  - BACKGROUND: Despite the marked increase of diverticulosis, its risk factors have
      not been adequately elucidated. We therefore aim to identify significantly
      associated factors with diverticulosis. We also aim to investigate the present
      state of diverticulosis in Japan. METHODS: We reviewed the medical records from
      1990 to 2010 that included the data of consecutive 62,503 asymptomatic
      colonoscopy examinees from the general population in Japan. Most recent 3,327
      examinees were analyzed with 16 background factors. RESULTS: Among the 62,503
      subjects (47,325 men and 15,178 women; 52.1 +/- 9.2 years old), diverticulosis
      was detected in 11,771 subjects (18.8%; 10,023 men and 1,748 women). The
      incidences of diverticulosis in 1990-2000 and 2001-2010 were respectively 13.0%
      (3,771 of 29,071) and 23.9% (8,000 of 33,432): the latter was much higher than
      the former in all age groups and for both genders. Considering the anatomical
      locations of colorectal diverticula, left-sided ones have markedly increased with
      age but not significantly changed with times. Univariate analyses of the 3,327
      subjects showed significant association of diverticulosis with four basic factors
      (age, sex, body mass index, blood pressure), three life style-related factor
      (smoking, drinking, severe weight increase in adulthood), and two blood test
      values (triglyceride, HbA1c). The multiple logistic analysis calculating
      standardized coefficients (beta) and odds ratio (OR) demonstrated that age (beta
      = 0.217-0.674, OR = 1.24-1.96), male gender (beta = 0.185, OR = 1.20), smoking
      (beta = 0.142-0.200, OR = 1.15-1.22), severe weight increase in adulthood (beta =
      0.153, OR = 1.17), HbA1c (beta = 0.136, OR = 1.15), drinking (beta = 0.109, OR =
      1.11), and serum triglyceride (beta = 0.098, OR = 1.10) showed significantly
      positive association with diverticulosis whereas body mass index and blood
      pressure did not. CONCLUSIONS: The large-scale data of asymptomatic colonoscopy
      examinees from the general population from 1990 to 2010 indicated that the
      prevalence of diverticulosis is still increasing in Japan. Age, male gender,
      smoking, severe weight increase in adulthood, serum HbA1c, drinking, and serum
      triglyceride showed significant positive association with diverticulosis.

PMID- 25860674
TI  - [Short vs long agonist protocols in poor responders undergoing IVF].
AB  - AIM: Compare among poor responders: stimulation results, laboratory parameters
      and the final IVF results by assessing 2 different stimulation protocols: the
      long agonist protocol and the short agonist protocol. METHODS: An analytical
      retrospective study carried out over of period of 2 years: January 2006 and
      December 2007. During this period, a total of 1192 IVF cycles of ICSI type were
      performed in 892 patients. INCLUSION CRITERIA: short agonist or antagonist
      stimulated patients protocols and presenting two of the three following criteria:
      1- Patients aged more than 38 years with an FSH plasmatic rate on the 3rd day of
      the cycle 9.5 UI/ml. 2- Antral follicle count (AFC) 5 for both ovaries. 3-
      Failure of anterior ovary stimulation: abandonment of cycle or 3 oocytes at data
      collection in a previous cycle. EXCLUSION CRITERIA: PCOS or single ovary.
      RESULTS: 65 patients, undergoing 92 attempts of ICSI cycles have been included in
      this study. Long agonist protocol was performed in 48 cases and Short agonist
      protocol was performed in 44 cycles. Both groups were comparable as to age (40,09
      +/- 6, 59 vs 41, 04 +/- 1,71 years; NS), BMI (25,2+/-3,92 vs 25,35+/-4,09 Kgm-2 ;
      NS), infertility type (primary 41% vs 59%;NS ; ou secondary 58% vs 40,9% ; NS),
      FSH (9,98+/-2,42 vs 10,01+/-2,75 ; NS) and antral follicle count on day 3 (4,13+/
      1,12 vs 3,8+/-1,16 FA ; NS). The estradiol rate, dosed on the onset day was
      significantly higher in the short protocol group (1534,27+/-1034,34 vs 1133,31+/
      1053,58 pg/ml; p=0.034). However, the consumed quantity of gonadotrophins was
      lower in the short protocol group (1550+/-235,45 vs 1725,55+/-450,35 UI, p=0.01).
      A total of 13 cycles was stopped: 9 times for the long protocol (18.75 %) and 4
      times for the short protocol (9.09 %) with statistically significant difference.
      The number of collected oocytes was significantly higher in the short protocol
      (7,64+/-3,70 vs 4,55+/-2,01, P<0.001). We significantly obtained more embryos in
      the short protocol (4,31+/-2,9 vs 2,16+/-2,2 embryos ; p<0,001). With higher
      number of grade 1 embryos (2,61 vs 1,14 embryons; p<0.001).The results in terms
      of pregnancy and living births show no significant difference between the 2
      groups. CONCLUSION: The short protocol is more suited to the profile of ovarian
      poor responders. The long protocol standard has no place in poor responders.
      However, the long micro dose protocol and the long degressed micro dose protocol
      yield results at least equivalent to the short protocol.

PMID- 25860675
TI  - Sudden death due to pulmonary embolism in north Tunisia: 37 cases study.
AB  - AIM: To determine frequency of pulmonary embolism as the cause of sudden death
      and to study clinical, epidemiological characteristics and risk factors. METHODS:
      Prospective study of cases of sudden death secondary to pulmonary embolism, whose
      autopsy was performed in the forensic department of Tunis, between October 2009
      and of September, 2011. RESULTS: During study period, 37 cases of pulmonary
      embolism were recorded. They represented 6.8 % of all cases of sudden
      cardiovascular deaths. Victims were male in most cases (65 %). Victims were aged
      between 21 and 87 years with an average age of about 52 years. Pathological
      histories were noted in 9 cases: three cases of recent surgery, four cases of
      pelvic trauma, a case of ovarian tumor and a case of which the PE arose in post
      partum. Concerning other risk factors of pulmonary embolism, confinement to bed
      was noted in 24 cases (64.8 %), obesity in 12 cases (32.4 %), an arterial high
      blood pressure in 4 cases. Histories of psychiatric pathology were noted in 5
      cases (13.5 %). Symptomatology preceding death was dominated by sudden death (35
      %) followed by dyspnoea (30 %) and thoracic pains (16 %). In 8 cases , victims
      consulted emergencies within 48 hours preceding death, for a varied
      symptomatology without diagnosis of pulmonary embolism is suspected. At autopsy,
      in 30 cases embolism was massive. In 29 % of the cases, a deep venous thrombosis
      was revealing in particular at the primitive iliac veins. CONCLUSION: Pulmonary
      embolism is an affection that still kills a lot. It can benefit from prevention
      and from an effective treatment. This testifies the major importance of clinical
      diagnosis of pulmonary embolism as well as the technical means for the diagnosis.

PMID- 25860676
TI  - [Postpartum depression: prevalence and risk factors. A prospective Study
      concerning 302 Tunisian parturients].
AB  - BACKGROUND: Depression is a common condition especially in the postpartum. It
      exposes mothers, newborns and couples for psychosocial complications. AIMS: They
      were to estimate the prevalence of the depression in postpartum in a population
      of 302 Tunisian parturients and to identify its associated factors. METHODS: Our
      study was prospective, in two stages: at the first week (T1), then between sixth
      and tenth week of the postpartum (T2). The study was conducted at CHU Hedi Chaker
      in Sfax, Tunisia. We used the Arabic version and validated the Edinburgh
      Postnatal Depression Scale (EPDS) for screening for postpartum depression. We
      used the scale MSSS. "Maternity Social Support Scale"to assess the social and
      family support and the Azrin scale to evaluate the satisfaction of the conjugal
      relationship. An epidemiologic questionnaire was used to collect the
      sociodemographic and clinical data. RESULTS: At T1, 302 women were examined. At
      T2, 139 were reexamined (46% of the initial population). In the first stage, the
      prevalence of the intense postpartum blues, according to EPDS, was 19,2%. In the
      second stage, the prevalence of the postnatal depression was 12, 9%. Factors
      associated with postpartum blues intense were the low socioeconomic status (p =0,
      01), a lower educational level (p = 0,017), the poor marital relationship (p =0,
      04), an insufficient social support (p 0,001), the difficulty to accept pregnancy
      (p =0,001), the presence of psychiatric the presence of psychiatric history (p
      =0,001), the prematurity (p =0,001) and an ill newborn birth (p =0,001). Factors
      associated with the post natal depression were the low socioeconomic status (p
      =0,01), the poor marital relationship (p =0,034), difficulty with pregnancy (p
      =0,001) and the presence of psychiatric history (p =0,001). CONCLUSION:
      Postpartum depressions are common. It seems to be the result of the interaction
      of several biological, psychological and social factors. This suggests the
      importance of screening for women having such risk factors to prevent the
      installation of this depression. This detection should be done early in
      postpartum or else in the later postnatal consultations. This allows an adequate
      treatment for the mothers, for the relationship mother-new born and later, for
      the psychological equilibrium of the child.

PMID- 25860677
TI  - [Immunohistochemical analysis of mismatch repair proteins in colorectal
      adenomas].
AB  - BACKGROUND: The deficiency of mismatch repair system is one of the main pathways
      in colorectal cancer. This system consists mainly of four proteins: MLH1, MSH2,
      MSH6 and PMS2. Colorectal cancer develops in the majority of cases from
      precancerous lesions called adenomas. Only few studies have reported on the
      deficiencies of these proteins in adenomas. AIM: In this study we used
      immunohistochemistry staining in colorectal adenomas to assay functional status
      of MLH1, MSH2, MSH6, and PMS2 proteins. METHODS: 102 adenomas from 93 patients
      were collected in our institution during six years (2007-2012). The
      immunohistochemical technique was performed with 4 antibodies: MLH1, MSH2, MSH6
      and PMS2. The loss of expression was retained if adenomatous cells were not
      stained with positive internal control. Staining was considered as abnormal if
      nucleus of adenomatous cells showed low nuclear staining and / or heterogeneous
      one, while positive internal control had normal staining. RESULTS: Loss of
      expression of MSH2 and MSH6 in adenomatous cells was found in only 1 case which
      was a tubular adenoma 3mm high-grade dysplasia. Abnormal staining of the
      adenomatous cells was noted in 23 cases (22.5%) for MSH2 and in 8 cases (7.8%)
      for MSH6. No cases showed loss of expression of MLH1 and PMS2. Abnormal
      expression of MSH2 and MSH6 was not correlated with sex of patients, the location
      of the adenoma, its grade of dysplasia and its histological type. CONCLUSIONS:
      Loss of Mismatch repair proteins expression is a rare event in adenomas. However,
      the abnormal expression levels are higher in our study compared to those reported
      in the literature. This could reflect a higher rate of microsatellite instability
      in our patients. Multicenter and larger studies with molecular biology techniques
      are needed.

PMID- 25860678
TI  - [Lupus nephritis: frequency, histological forms and predictors of renal disease].
AB  - BACKGROUND: Lupus nephritis is a common and serious damage in systemic lupus
      erythematosus. The aim of our study is to define the frequency and to identify
      the predictors of lupus nephritis in patients with systemic lupus erythematosus.
      METHODS: multicenter retrospective study on all systemic lupus erythematosus
      patients followed between 2005 and 2012. We analyzed the epidemiological,
      clinical and biological presentation at admission and during follow-up. We have
      identified two groups of patients: group 1 involving systemic lupus erythematosus
      without renal disease, group 2 : patient with lupus nephritis. RESULTS: We
      collected 105 patients including 100 women, 41 (39%) with lupus nephritis
      occurred after a period of 30+/-10 months of development of lupus. 4 patients
      (3%) were initially presented with acute renal failure requiring hemodialysis.
      The pathological findings of renal biopsy is respectively: class IV, III and II
      in 19 patients (63.3%), 4 patients (13.3%), and 4 patients (13.3%). Our patients
      with lupus nephritis received various treatment regimens: 38 patients (92.7%)
      received corticosteroids and combined with cyclophosphamide in 33 (80.5%) cases.
      Only young age, anemia and antinuclear antibodies were correlated with the risk
      of occurrence of renal damage. Predictors of the severity of lupus nephritis were
      the short time of occurrence of renal and renal failure. CONCLUSION: Lupus
      nephritis in our series is characterized by a severity of the clinical and
      biological explained by the frequency of proliferative forms, hence the necessity
      for early and adequate management.

PMID- 25860679
TI  - [Sacroiliac joint disorders in Abidjan: epidemiological, clinical, radiological
      and etiological characteristics].
AB  - BACKGROUND: The sacroiliac joint remains unknown in sub-Saharan Africa. Studies
      about the sacroiliac diseases are rare Aim : Describe the epidemiological,
      clinical, radiological and etiological characteristics of sacroiliac joint
      diseases in Abidjan Methods : Retrospective and descriptive study concerning 17
      patients hospitalized from February 2003 to April 2010 in the department of
      rheumatology of university hospital center of Cocody (Abidjan) for buttock pain
      or others functional signs evoking sacroiliac joint which were attested by
      radiographic lesions. We were interested on the epidemiological, clinical and
      radiological characteristics and the etiologies in the sacroiliac disease.
      RESULTS: The hospital prevalence of sacroiliac diseases was 0.55% corresponding
      in 17 of 3067 rheumatological diseases. The female sex predominated (82.35%) and
      the mean age of 25.58 years. Gyneco-obstetric events were the predominant risk
      factors (47.05%). Sacroiliac damage was manifested by inflammatory pain (64.7%)
      localized at the buttock or lumbar spine, radiating to the thigh (52.9%) and was
      accompanied by functional disability (82.2%) and fever was not present every time
      (64.7%). The physical findings were the tripod sign positive (58.8%), the
      monopodal backing positive (41.2%) and palpation painful of sacroiliac joint. The
      standard radiograph revealed a blurring aspect and widening of joint space
      associated with demineralization (68.4%), a joint space narrowing and erosion of
      articular banks (23.5%). The etiologies found were bacterial arthritis (82.3%)
      mainly pyogenic (70.58%), osteoarthritis (11.7%) and ankylosing spondylitis
      (5.9%). CONCLUSION: Sacroiliac joint diseases are rare in rheumatology practice
      in Abidjan, concern younger subjects and are dominated by pyogenic sacroiliitis.

PMID- 25860680
TI  - [Consequences of hysterectomy at the national- hospital of Pikine in Dakar].
AB  - BACKGROUND: Despite the frequency of hysterectomy, several studies have reported
      physical and psychological sequelae of this intervention. BUT: To evaluate the
      consequences of hysterectomy, their level of importance and how patients
      experience hysterectomy. METHODS: That is a prospective study of 70 patients who
      underwent a hysterectomy from January 2009 to June 2011 at Pikine National
      Hospital. The experience of hysterectomy was determined by the physical and
      psychosocial felt after surgery. RESULTS: Hysterectomy represented 5.9 % of
      gynecological surgical activities. The indications were dominated by myoma
      (57.1%). Hysterectomy was performed abdominally in 78.6% of cases and associated
      with bilateral salpingo-oophorectomy in 87% of cases. After surgery, new symptoms
      appeared: hot flushes, night sweats, urinary incontinence and urge incontinence
      in respectively 65.7%, 54.3%, 7.1% and 11.4% of patients. A proportion of 45.6%
      of them had resumed sexual activity after 90 days. The fear of pain at the time
      of intercourse was expressed in 55.7% of cases. A decrease in the frequency of
      sexual intercourse was found in 54.3% of patients. A drop of pleasure during sex
      was expressed in 38.6% of patients. Psychological effects were also reported by
      patients: decreased confidence in 31.4% of patients, feeling of being rejected by
      her husband in 5.7% of cases, sensation of mutilation in 24.3% of cases.
      CONCLUSION: Physical and psychological postoperative impacts of hysterectomy are
      real. Adequate accompanying measures are necessary, in addition to preoperative
      preparation, to allow patients to improve the experience of hysterectomy.

PMID- 25860681
TI  - Autoimmune pancreatitis. A report of 5 cases from Tunisia: diagnostic challenge.
AB  - BACKGROUND: In this study, we aimed to review retrospectively the records of 5
      patients who were treated in our hospital and to review the current approaches in
      diagnosis and management of autoimmune pancreatitis (AIP). METHODS: The series of
      patients diagnosed with AIP during the last seven years (January 2006 - August
      2012) was the basis of this study. All records were retrieved and analyzed. The
      diagnosis of AIP was established on the basis of imaging studies, serology,
      cytology and response to treatment. RESULTS: Five patients were diagnosed with
      AIP pancreatitis during this 7-years period. Four of the 5 patients were males.
      The most common presenting symptom was abdominal pain (4/5). Two patients with
      the preliminary diagnosis of pancreatic mass underwent surgery. Histological
      analysis of the surgical resection did not reveal any malignancy. During the
      follow-up, one of them has developed Crohn's disease and Sjogren syndrome. One of
      the patients had obstructive jaundice and abdominal pain for several months.
      Abdominal contrast enhanced computed tomography (CECT) suggested the diagnosis of
      AIP, cholangitis with renal atrophy and retroperitoneal fibrosis. He was started
      on steroids to which he responded dramatically. One patient had been diagnosed as
      primary sclerosing cholangitis few months earlier on the basis of abdominal CECT
      features showing a dominant stricture in the common bile duct. During the follow
      up, the diagnosis of AIP was suspected and finally established on the basis of
      repeated magnetic resonance imaging (MRI). The last patient had history of acute
      pancreatitis, obstructive jaundice and abdominal pain for 3 months. An abdominal
      CECT suggested autoimmune pancreatitis which was confirmed by MRCP. He was
      started later on steroids to which he responded significantly. IgG4 was done in
      all cases, high in four patients. CONCLUSION: AIP is a disease with increasing
      incidence and characterized by lymphoplasmacytic cells infiltration and fibrosis.
      It is necessary to evaluate patients in terms of AIP serologically to avoid wrong
      diagnosis and the morbidity of surgery.

PMID- 25860682
TI  - Atrioventricular dissociation due to pheochromocytoma: a case report.

PMID- 25860683
TI  - [Leiomyosarcoma of bladder].

PMID- 25860684
TI  - [Abdominal pseudotumoral actinomycosis. A case report].

PMID- 25860685
TI  - Synchronous primary rectal and prostate cancers.

PMID- 25860686
TI  - [Sweet's syndrome: a rare cause of erysipeloid dermatitis].

PMID- 25860687
TI  - Small intestinal metastases: an unusual initial manifestation of lung carcinoma.

PMID- 25860688
TI  - [Pathological fracture of the femoral neck revealing a fibrous dysplasia of
      bone].

PMID- 25860689
TI  - [Cytomegalovirus infection simulating an overlap syndrome: autoimmune hepatitis 
      primary biliary cirrhosis].

PMID- 25860690
TI  - Urinary bladder metastasis from breast carcinoma.

PMID- 25860691
TI  - Alteration of Wax Ester Content and Composition in Euglena gracilis with Gene
      Silencing of 3-ketoacyl-CoA Thiolase Isozymes.
AB  - Euglena gracilis produces wax ester under hypoxic and anaerobic culture
      conditions with a net synthesis of ATP. In wax ester fermentation, fatty acids
      are synthesized by reversing beta-oxidation in mitochondria. A major species of
      wax ester produced by E. gracilis is myristyl myristate (14:0-14:0Alc). Because
      of its shorter carbon chain length with saturated compounds, biodiesel produced
      from E. gracilis wax ester may have good cold flow properties with high oxidative
      stability. We reasoned that a slight metabolic modification would enable E.
      gracilis to produce a biofuel of ideal composition. In order to produce wax ester
      with shorter acyl chain length, we focused on isozymes of the enzyme 3-ketoacyl
      CoA thiolase (KAT), a condensing enzyme of the mitochondrial fatty acid synthesis
      pathway in E. gracilis. We performed a gene silencing study of KAT isozymes in E.
      gracilis. Six KAT isozymes were identified in the E. gracilis EST database, and
      silencing any three of them (EgKAT1-3) altered the wax ester amount and
      composition. In particular, silencing EgKAT1 induced a significant compositional
      shift to shorter carbon chain lengths in wax ester. A model fuel mixture inferred
      from the composition of wax ester in EgKAT1-silenced cells showed a significant
      decrease in melting point compared to that of the control cells. 

PMID- 25860692
TI  - The effects of omega-3 polyunsaturated Fatty Acid consumption on mammary
      carcinogenesis.
AB  - The consumption of omega-3 polyunsaturated fatty acids (n-3 PUFA) is associated
      with a reduced risk of breast cancer. Studies in animals and in vitro have
      demonstrated mechanisms that could explain this apparent effect, but clinical and
      epidemiological studies have returned conflicting results on the practical
      benefits of dietary n-3 PUFA for prevention of breast cancer. Effects are often
      only significant within a population when comparing the highest n-3 PUFA
      consumption group to the lowest n-3 group or highest n-6 group. The beneficial
      effects of n-3 PUFA eicosapentaenoic and docosahexaenoic on the risk of breast
      cancer are dose dependent and are negatively affected by total n-6 consumption.
      The majority of the world population, including the most highly developed
      regions, consumes insufficient n-3 PUFA to significantly reduce breast cancer
      risk. This review discusses the physiological and dietary context in which
      reduction of breast cancer risk may occur, some proposed mechanisms of action and
      meaningful recommendations for consumption of n-3 PUFA in the diet of developed
      regions. 

PMID- 25860693
TI  - GeneSippr: a rapid whole-genome approach for the identification and
      characterization of foodborne pathogens such as priority Shiga toxigenic
      Escherichia coli.
AB  - The timely identification and characterization of foodborne bacteria for risk
      assessment purposes is a key operation in outbreak investigations. Current
      methods require several days and/or provide low-resolution characterization. Here
      we describe a whole-genome-sequencing (WGS) approach (GeneSippr) enabling same
      day identification of colony isolates recovered from investigative food samples.
      The identification of colonies of priority Shiga-toxigenic Escherichia coli
      (STEC) (i.e., serogroups O26, O45, O103, O111, O121, O145 and O157) served as a
      proof of concept. Genomic DNA was isolated from single colonies and sequencing
      was conducted on the Illumina MiSeq instrument with raw data sampling from the
      instrument following 4.5 hrs of sequencing. Modeling experiments indicated that
      datasets comprised of 21-nt reads representing approximately 4-fold coverage of
      the genome were sufficient to avoid significant gaps in sequence data. A novel
      bioinformatic pipeline was used to identify the presence of specific marker genes
      based on mapping of the short reads to reference sequence libraries, along with
      the detection of dispersed conserved genomic markers as a quality control metric
      to assure the validity of the analysis. STEC virulence markers were correctly
      identified in all isolates tested, and single colonies were identified within 9
      hrs. This method has the potential to produce high-resolution characterization of
      STEC isolates, and whole-genome sequence data generated following the GeneSippr
      analysis could be used for isolate identification in place of lengthy biochemical
      characterization and typing methodologies. Significant advantages of this
      procedure include ease of adaptation to the detection of any gene marker of
      interest, as well as to the identification of other foodborne pathogens for which
      genomic markers have been defined. 

PMID- 25860695
TI  - Inhibition of TRB3 Protects Photoreceptors against Endoplasmic Reticulum Stress
      Induced Apoptosis after Experimental Retinal Detachment.
AB  - PURPOSE: To investigate the expression of tribbles homologue 3 (TRB3) and its
      regulation on endoplasmic reticulum stress (ERS)-induced photoreceptor apoptosis
      after retinal detachment (RD) using a rat model. METHODS: RD animal model was
      created in Wistar rats by subretinal injection of 1% sodium hyaluronate. At
      various time points after RD, expression of TRB3 was detected by quantitative
      real-time PCR and Western blotting. TRB3 protein distribution in retina was
      evaluated by immunohistochemistry. RNA interference was used to inhibit TRB3
      expression and subretinal injection of lentivirus TRB3 shRNA (LV-TRB3-sh) was
      performed. The rats were then randomly divided into four groups: normal control
      group, RD group, vehicle + RD group and LV-TRB3-sh + RD group. The mRNA and
      protein level of TRB3 as well as Caspase-12 were detected. TdT-mediated
      fluorescein-16-dUTP nick-end labeling (TUNEL) assay was used to detect the
      apoptosis of retinal cells. Retinal outer nuclear layer (ONL) thickness was
      measured to assess retina damage in each group. RESULTS: TRB3 expression and TRB3
      positive cell count were significantly increased after RD and peaked at day 3
      after RD. The ratio of TUNEL-positive photoreceptors and expression of ERS
      induced apoptosis marker Caspase-12 in LV-TRB3-sh + RD group were significantly
      reduced. The ONL thickness in LV-TRB3-sh + RD group was thicker than that both in
      RD group and vehicle + RD group. CONCLUSION: TRB3 expression is up-regulated in
      retinas after RD and knockdown of TRB3 protects photoreceptors against ERS
      induced apoptosis. TRB3 may be a crucial molecule in photoreceptor apoptosis
      induced by ERS after RD.

PMID- 25860694
TI  - N-ethyl-N-Nitrosourea (ENU) induced mutations within the klotho gene lead to
      ectopic calcification and reduced lifespan in mouse models.
AB  - Ectopic calcification (EC), which is the pathological deposition of calcium and
      phosphate in extra-skeletal tissues, may be associated with hypercalcaemic and
      hyperphosphataemic disorders, or it may occur in the absence of metabolic
      abnormalities. In addition, EC may be inherited as part of several monogenic
      disorders and studies of these have provided valuable insights into the metabolic
      pathways regulating mineral metabolism. For example, studies of tumoural
      calcinosis, a disorder characterised by hyperphosphataemia and progressive EC,
      have revealed mutations of fibroblast growth factor 23 (FGF23), polypeptide N
      acetyl galactosaminyltransferase 3 (GALNT3) and klotho (KL), which are all part
      of a phosphate-regulating pathway. However, such studies in humans are limited by
      the lack of available large families with EC, and to facilitate such studies we
      assessed the progeny of mice treated with the chemical mutagen N-ethyl-N
      nitrosourea (ENU) for EC. This identified two mutants with autosomal recessive
      forms of EC, and reduced lifespan, designated Ecalc1 and Ecalc2. Genetic mapping
      localized the Ecalc1 and Ecalc2 loci to a 11.0 Mb region on chromosome 5 that
      contained the klotho gene (Kl), and DNA sequence analysis identified nonsense
      (Gln203Stop) and missense (Ile604Asn) Kl mutations in Ecalc1 and Ecalc2 mice,
      respectively. The Gln203Stop mutation, located in KL1 domain, was severely
      hypomorphic and led to a 17-fold reduction of renal Kl expression. The Ile604Asn
      mutation, located in KL2 domain, was predicted to impair klotho protein stability
      and in vitro expression studies in COS-7 cells revealed endoplasmic reticulum
      retention of the Ile604Asn mutant. Further phenotype studies undertaken in Ecalc1
      (kl203X/203X) mice demonstrated elevations in plasma concentrations of phosphate,
      FGF23 and 1,25-dihydroxyvitamin D. Thus, two allelic variants of Kl that develop
      EC and represent mouse models for tumoural calcinosis have been established. 

PMID- 25860697
TI  - Design-support and performance estimation using HYDRUS/CW2D: a horizontal flow
      constructed wetland for polishing SBR effluent.
AB  - The 4,000 PE (700 m(3)/d) wastewater treatment plant at Balf, Hungary was based
      on sequencing batch reactor technology with phosphorus precipitation as the
      tertiary step. Its effluent met quality thresholds on average, with above
      threshold peaks mainly in winter. The HYDRUS/CW2D model package (PC Progress
      s.r.o.) was used to simulate the treatment performance of a horizontal flow
      constructed wetland for polishing effluent. The goal of this study was to provide
      design-supportive information about the suitability of the proposed wetland and
      to prove the applicability of the computational tool used to gain that
      information. The simulations showed that the wetland with the proposed layout
      could not tackle peaks in NH4-N. Other effluent thresholds could be met,
      including chemical oxygen demand (COD), biochemical oxygen demand (BOD5), total
      nitrogen, total inorganic nitrogen and total phosphorus. The tool was unable to
      simulate COD and BOD5 removal in periods when the electron acceptors were
      depleted because anaerobic processes are not modelled. Using a tool of such
      complexity for designing carries excessive work demands and involves many
      uncertainties. The simulation study highlighted that the model used could still
      facilitate the design of an effective system by showing the weaknesses of a test
      scenario as it was demonstrated. 

PMID- 25860696
TI  - Application of lipase from Burkholderia cepacia in the degradation of agro
      industrial effluent.
AB  - This study aimed to analyze the physical and chemical characteristics of Amano PS
      commercial lipase - Burkholderia cepacia and lipase produced by Burkholderia
      cepacia strain ATCC 25416, in addition to studying the hydrolysis of agro
      industrial effluent collected in a fried potato industry. The optimum temperature
      for increasing lipase activity was 37  degrees C. The temperature increase caused
      a decrease in thermostability of lipase, and the commercial lipase was less
      stable, with values of 10.5, 4.6 and 4.9%, respectively, lower than those
      obtained by lipase from strain ATCC 25416, at temperatures of 40, 50 and 60 
      degrees C. The enzymatic activity was higher in alkaline conditions, achieving
      better results at pH 8.0. The pH was the variable that most influenced the
      hydrolysis of triacylglycerides of the agro-industrial effluent, followed by
      enzyme concentration, and volume of gum arabic used in the reaction medium. Thus,
      it can be observed that the enzymatic hydrolytic process of the studied effluent
      presents a premising contribution to reduction of environmental impacts of potato
      chip processing industries. 

PMID- 25860698
TI  - Modeling of organic substrate transformation in the high-rate activated sludge
      process.
AB  - This study describes the development of a modified activated sludge model No.1
      framework to describe the organic substrate transformation in the high-rate
      activated sludge (HRAS) process. New process mechanisms for dual soluble
      substrate utilization, production of extracellular polymeric substances (EPS),
      absorption of soluble substrate (storage), and adsorption of colloidal substrate
      were included in the modified model. Data from two HRAS pilot plants were
      investigated to calibrate and to validate the proposed model for HRAS systems. A
      subdivision of readily biodegradable soluble substrate into a slow and fast
      fraction were included to allow accurate description of effluent soluble chemical
      oxygen demand (COD) in HRAS versus longer solids retention time (SRT) systems.
      The modified model incorporates production of EPS and storage polymers as part of
      the aerobic growth transformation process on the soluble substrate and
      transformation processes for flocculation of colloidal COD to particulate COD.
      The adsorbed organics are then converted through hydrolysis to the slowly
      biodegradable soluble fraction. Two soluble substrate models were evaluated
      during this study, i.e., the dual substrate and the diauxic models. Both models
      used two state variables for biodegradable soluble substrate (SBf and SBs) and a
      single biomass population. The A-stage pilot typically removed 63% of the soluble
      substrate (SB) at an SRT <0.13 d and 79% at SRT of 0.23 d. In comparison, the
      dual substrate model predicted 58% removal at the lower SRT and 78% at the higher
      SRT, with the diauxic model predicting 32% and 70% removals, respectively.
      Overall, the dual substrate model provided better results than the diauxic model
      and therefore it was adopted during this study. The dual substrate model
      successfully described the higher effluent soluble COD observed in the HRAS
      systems due to the partial removal of SBs, which is almost completely removed in
      higher SRT systems. 

PMID- 25860699
TI  - Decreased UV absorbance as an indicator of micropollutant removal efficiency in
      wastewater treated with ozone.
AB  - Ozone transforms various organic compounds that absorb light within the UV and
      visible spectra. UV absorbance can therefore be used to detect the transformation
      of chemicals during ozonation. In wastewater, decolourisation can be observed
      after ozonation. This study investigates the correlation of the UV absorbance
      difference between the ozonation inlet and outlet and the removal efficiency of
      micropollutants in wastewater. The absorbance at 254 and 366 nm was measured at
      the ozonation inlet and outlet, as was the concentration of 24 representative
      micropollutants and the dissolved organic carbon (DOC). The results clearly
      showed that the relative decrease of absorbance (DeltaAbs) is positively
      correlated with the relative removal efficiency of micropollutants. We therefore
      suggest that UV absorbance can be used as a feedback control parameter to achieve
      optimal ozone dosage in wastewater treatment plants and to gain a fast insight
      into the process efficiency and stability of the ozonation. 

PMID- 25860700
TI  - The effects of different aeration modes on ammonia removal from sludge digester
      liquors in the nitritation-anammox process.
AB  - The aim of this study was to determine the impact of continuous and intermittent
      aeration on the rate of ammonia removal in the combined nitritation-anammox
      process. This process was run in two parallel sequencing batch reactors (SBRs),
      with a working volume V = 10 L, treating sludge digester liquors from the Gdansk
      (Poland) wastewater treatment plant (WWTP). The ammonia oxidizing bacteria were
      cultivated from activated sludge from the same plant, whereas the anammox
      bacteria originated from the Zurich WWTP (Switzerland). Both SBRs were operated
      with 12-h cycles, temperature 30  degrees C and hydraulic residence time between
      1 and 7 days depending on the operating period. The maximum specific ammonium
      utilization rate (sAUR) was observed in the reactor with intermittent aeration,
      and varied in the range of 4.4-4.7 g N kg VSS-1 h-1. The sAUR in the reactor with
      continuous aeration was slightly lower and ranged from 4.39 to 4.41 g N kg VSS-1
      h-1. In the case of intermittent aeration, the additional measurement was
      performed at two different dissolved oxygen concentrations, i.e., 1 and 0.8 mg
      O2L-1, and the observed nitrogen removal rates were 4.7 and 2.7 g N kg VSS-1 h-1,
      respectively.

PMID- 25860701
TI  - Comparative research on phosphorus removal by pilot-scale vertical flow
      constructed wetlands using steel slag and modified steel slag as substrates.
AB  - This research mainly focused on the phosphorus removal performance of pilot-scale
      vertical flow constructed wetlands with steel slag (SS) and modified steel slag
      (MSS). First, bench-scale experiments were conducted to evaluate the phosphorus
      adsorption capacity. Results showed that the Langmuir model could better describe
      the adsorption characteristics of the two materials; the maximum adsorption of
      MSS reached 12.7 mg/g, increasing by 34% compared to SS (9.5 mg/g). Moreover,
      pilot-scale constructed wetlands with SS and MSS were set up outdoors. Then, the
      influence of hydraulic retention time (HRT) and phosphorus concentration in
      phosphorus removal for two wetlands were investigated. Results revealed that
      better performance of the two systems could be achieved with an HRT of 2 d and
      phosphorus concentration in the range of 3-4.5 mg/L; the system with MSS had a
      better removal efficiency than the one with SS in the same control operation.
      Finally, the study implied that MSS could be used as a promising substrate for
      wetlands to treat wastewater with a high phosphorus concentration. However,
      considering energy consumption, SS could be regarded as a better alternative for
      substrate when treating sewage with a low phosphorus concentration. 

PMID- 25860702
TI  - Role of vegetation (Typha latifolia) on nutrient removal in a horizontal
      subsurface-flow constructed wetland treating UASB reactor-trickling filter
      effluent.
AB  - The main objective of the work is to characterize the role of plants in a
      constructed wetland in the removal of nitrogen (N) and phosphorus (P). The
      experiments were carried out in a full-scale system in the city of Belo
      Horizonte, Brazil, with two parallel horizontal subsurface-flow constructed
      wetland units (one planted with Typha latifolia and one unplanted) treating the
      effluent from a system composed of an upflow anaerobic sludge blanket reactor and
      a trickling filter (TF). Each wetland unit received a mean flow of approximately
      8.5 m3 d-1 (population equivalent around 60 inhabitants each), with a surface
      hydraulic loading rate 0.12 m3m-2d-1. The experiments were conducted from
      September 2011 to July 2013. Mean effluent concentrations from the wetlands were:
      (a) planted unit total nitrogen (TN) 22 mg L-1, ammonia-N 19 mg L-1, nitrite-N
      0.10 mg L-1, nitrate-N 0.25 mg L-1, P-total 1.31 mg L-1; and (b) unplanted unit
      TN 24 mg L-1, ammonia-N 20 mg L-1, nitrite-N 0.54 mg mL-1, nitrate-N 0.15 mg L-1,
      P-total 1.31 mg L-1. The aerial part of the plant contained mean values of 24.1
      gN (kg dry matter)-1 and 4.4 gP (kg dry matter)-1, and the plant root zone was
      composed of 16.5 gN (kg dry matter)-1 and 4.1 gP (kg dry matter)-1. The mean
      extraction of N by the plant biomass was 726 kgN ha-1y-1, corresponding to 17% of
      the N load removed. For P, the extraction by the plant biomass was 105 kgP ha-1y
      1, corresponding to 9% of the P load removed. These results reinforce the reports
      that N and P removal due to plant uptake is a minor mechanism in horizontal
      subsurface-flow constructed wetlands operating under similar loading rates,
      typical for polishing of sanitary effluent.

PMID- 25860703
TI  - Greenhouse gas emissions from sludge treatment reed beds.
AB  - Sludge treatment reed bed systems (STRBs) are considered as an alternative
      technology for surplus sludge treatment. Organic matter is decomposed by various
      microbial reactions, resulting in gases such as CO2and CH4emitting into the
      atmosphere. The aim of this study is to investigate gas emission from STRBs. The
      static transparent chamber was adopted to measure gas emission; it allows
      sunlight to enter and plants to photosynthesise. The comparison of total solids
      and volatile solids showed STRBs have a higher efficiency in dewatering and
      mineralization than a conventional unplanted sludge drying bed (USDB). The
      CO2emission ranged from 28.68 to 100.42 g CO2m-2 d(-1) in USDB, from 16.48 to
      65.18 g CO2m-2 d-1 in STRBs; CH4emission ranged from 0.26 to 0.99 g CH4 m-2 d-1
      in USDB, from 0.43 to 1.95 g CH4m-2 d-1 in STRBs. Both gas fluxes decreased
      towards the end of vegetation and reached the highest rates during the hot and
      dry summer. After the system was loaded by sludge, the fluxes of CO2and
      CH4significantly decreased in the USDB, whereas they increased in STRBs. In terms
      of CO2equivalent, the global warming potential of CH4was 13.13 g CO2eq m-2 d-1
      and 15.02 g CO2eq m-2 d-1 in USDB and STRBs, respectively.

PMID- 25860704
TI  - Comparison of denitrification performances using PLA/starch with different mass
      ratios as carbon source.
AB  - A suitable carbon source is significant for biological nitrate removal from
      groundwater. In this study, slow-release carbon sources containing polylactic
      acid (PLA) and starch at 8:2, 7:3, 6:4, 5:5, 4:6, and 3:7 ratios were prepared
      using a blending and fusing technique. The PLA/starch blend was then used as a
      solid carbon source for biological nitrate removal. The carbon release rate of
      PLA/starch was found to increase with increased starch content in leaching
      experiments. PLA/starch at 5:5 mass ratio was found to have the highest
      denitrification performance and organic carbon consumption efficiency in semi
      continuous denitrification experiments, and was also revealed to support complete
      denitrification at 50 mg-N/L influent nitrate concentration in continuous
      experiments. The effluent nitrate concentration was <2 mg NO(3)(-)-N/L, which met
      the national standard (GB 14848-93) for groundwater. Scanning electron microscopy
      results further showed that the surface roughness of PLA/starch increased with
      prolonged experimental time, which may be conducive to microorganism attachment.
      Therefore, PLA/starch was a suitable carbon source and biofilm carrier for
      groundwater remediation.

PMID- 25860705
TI  - The process of activated sludge ozonation: effect of ozone on cells, flocs,
      macromolecules and nutrient release.
AB  - The purpose of this research is to investigate the activated sludge ozonation
      process. Results revealed that bacteria destruction and cell solubilization were
      not obvious when ozone dose was lower than 11 mgO3/gMLSS (MLSS: mixed liquor
      suspended solids), while pores appeared on the sludge and bacterial disappeared
      from floc surface. In the range of 11-90 mgO3/gMLSS, ozone had significant effect
      on cell permeabilization and disruption. Meanwhile, a large quantity of
      macromolecules and nutrients were released from bacteria cells. Additionally,
      efficiency of ozone utilization was low but specific solubilization related to
      cell lysis was high at this level. Greater than 90 mgO3/gMLSS, the number of live
      cells and dead cells were both stable, and the quantity of material in bulk
      liquid increased slowly. The specific solubilization ratio decreased while the
      efficiency of ozone utilization began to increase. This indicated that ozone
      oxidized the macromolecules in the bulk liquid instead of bacteria cells at high
      ozone dose.

PMID- 25860706
TI  - Assimilation of satellite data to 3D hydrodynamic model of Lake Sakylan
      Pyhajarvi.
AB  - To analyze the applicability of direct insertion of total suspended matter (TSM)
      concentration field based on turbidity derived from satellite data to numerical
      simulation, dispersion studies of suspended matter in Lake Sakylan Pyhajarvi
      (lake area 154 km2; mean depth 5.4 m) were conducted using the 3D COHERENS
      simulation model. To evaluate the practicality of direct insertion, five cases
      with different initialization frequencies were conducted: (1) every time, when
      satellite data were available; (2) every 10 days; (3) 20 days; (4) 30 days; and
      (5) control run without repeated initialization. To determine the effectiveness
      of initialization frequency, three methods of comparison were used: simple
      spatial differences of TSM concentration without biomass in the lake surface
      layer; averaged spatial differences between initialization data and the
      forecasts; and time series of TSM concentration and observation data at 1 m depth
      at the deepest point of the lake. Results showed that direct insertion improves
      the forecast significantly, even if it is applied less often.

PMID- 25860707
TI  - Aerobic granular sludge technology and nitrogen removal for domestic wastewater
      treatment.
AB  - This study evaluated aerobic granulation and nitrogen removal via assimilation,
      nitrification, and denitrification of a system fed with real domestic wastewater.
      The granulation process was complete after 160 days of operation. The mature
      granules had an almost spherical structure, an average size of 473.0 MUm, and a
      good settling ability (SVI30 of 75.6 mL g-1). Ammonium assimilation for cell
      growth varied between 3.5 and 64.6% during reactor start-up. After granule
      formation, assimilation accounted for less than 5% and nitrogen was mainly
      removed by partial nitrification up to nitrite, followed by denitrification via
      nitrite. Average efficiencies of 86.6% for nitrification, 59.5% for
      denitrification, and 60.5% for total nitrogen were obtained in this period. The
      assimilation ability of the mature granules grown on domestic wastewater was
      lower than the commonly reported results obtained for synthetic granules.

PMID- 25860708
TI  - Application of the environmental Gini coefficient in allocating water governance
      responsibilities: a case study in Taihu Lake Basin, China.
AB  - The equitable allocation of water governance responsibilities is very important
      yet difficult to achieve, particularly for a basin which involves many
      stakeholders and policymakers. In this study, the environmental Gini coefficient
      model was applied to evaluate the inequality of water governance responsibility
      allocation, and an environmental Gini coefficient optimisation model was built to
      achieve an optimal adjustment. To illustrate the application of the environmental
      Gini coefficient, the heavily polluted transboundary Taihu Lake Basin in China,
      was chosen as a case study. The results show that the original environmental Gini
      coefficient of the chemical oxygen demand (COD) was greater than 0.2, indicating
      that the allocation of water governance responsibilities in Taihu Lake Basin was
      unequal. Of seven decision-making units, three were found to be inequality
      factors and were adjusted to reduce the water pollutant emissions and to increase
      the water governance inputs. After the adjustment, the environmental Gini
      coefficient of the COD was less than 0.2 and the reduction rate was 27.63%. The
      adjustment process provides clear guidance for policymakers to develop
      appropriate policies and improve the equality of water governance responsibility
      allocation. 

PMID- 25860709
TI  - Integrated side-stream reactor for biological nutrient removal and minimization
      of sludge production.
AB  - Integrated processes to reduce in situ the sludge production in wastewater
      treatment plants are gaining attention in order to facilitate excess sludge
      management. In contrast to post-treatments, such as anaerobic digestion which is
      placed between the activated sludge system and dewatering processes, integrated
      technologies are placed in the sludge return line. This study evaluates the
      application of an anoxic side-stream reactor (SSR) which creates a physiological
      shock and uncouples the biomass metabolism and diverts the activity from
      assimilation for biosynthesis to non-growth activities. The effect of this system
      in biological nutrient removal for both nitrogen and phosphorus was evaluated for
      the anaerobic, anoxic and aerobic reactors. The RedOx potential within the SSR
      was maintained at -150 mV while the sludge loading rate was modified by
      increasing the percentage of recycled activated sludge feed to the SSR (0 and 40%
      at laboratory scale and 0, 10, 50 and 100% at pilot scale). The use of the SSR
      presented a slight reduction of phosphorus removal but maintained the effluent
      quality to the required discharge values. Nitrogen removal efficiency increased
      from 75 to 86% while reducing the sludge production rate by 18.3%. 

PMID- 25860710
TI  - Characteristics and indications of hydrogen and oxygen isotopes distribution in
      lake ice body.
AB  - Stable isotopes have been used to identify the characteristics of precipitation,
      evaporation, basin hydrology, and residence times. However, lakes in the cold
      regions are usually covered by ice for 5-6 months. To get a better understanding
      of stable isotopes characteristics and indications in lake ice bodies, ice and
      water were sampled during the icebound season in both the ice and water bodies in
      Dali Lake, and deuterium, oxygen-18 total nitrogen (TN), and the major ions were
      analyzed. The results showed that deuterium and oxygen-18 compositions (deltaD
      delta18O) compositions in the ice body were greater than in the water body
      beneath, scattered on a straight line, and deviating downward from the global
      meteoric water line in the top right. The ice profile showed that the deltaD
      delta18O compositions increased from the ice surface downward and decreased near
      to the bottom. In contrast, the TN and the major ions in the ice decreased from
      the ice surface downward and increased near to the bottom, meaning that the
      concentrations of delta18O had a negative correlation with the concentrations of
      TN and major ions. These indicated that stable isotopes can be used for tracing
      the nutriment and ion transport processes in the ice body.

PMID- 25860711
TI  - Integrating activated sludge floc size information in MBR fouling modeling.
AB  - Although studied extensively, modeling fouling phenomena in membrane bioreactors
      (MBRs) remains challenging. It has been well established that cake layer
      formation and pore blocking have a strong impact on the filtration performance
      but how to capture that in comprehensive models is not fully defined yet. Since
      it has been shown that bioflocculation characteristics of activated sludge have a
      clear link with (the extent of) membrane fouling, this study integrates activated
      sludge floc size (i.e., particle size distribution) information in the model for
      pore blocking and cake layer formation with a focus on constant flux operated
      MBRs. Based on these floc size distributions, a three-dimensional modeling and
      visualization of the cake layer is envisaged which can then provide the required
      input information (e.g., the porosity of the cake layer) for the fouling model.
      The model is calibrated and validated on the basis of experimental data from
      Hwang et al. (2012) in 'Membrane bioreactor: TMP rise and characterization of
      biocake structure using CLSM-image analysis' (see J. Membr. Sci. 419-420, 33-41).

PMID- 25860712
TI  - Autotrophic denitrification with anaerobic Fe(2+) oxidation by a novel
      Pseudomonas sp. W1.
AB  - In the present study, a novel Pseudomonas sp. W1 was characterized in terms of
      its ability to perform nitrate removal coupled with anaerobic Fe-1 oxidation
      under autotrophic growth condition. The effects of operating parameters with
      respect to the initial solution pH, temperature and initial Fe-1 concentration on
      nitrate removal were investigated by central composite design. Based on the
      results of response surface methodology, the maximal nitrate removal efficiency
      was achieved under the following conditions: pH 7.0, temperature 30  degrees C
      and initial Fe-1 concentration 1,100 mg L-1. Under this optimal condition and
      with an initial NO(3)(-)-N concentration of 55 mg L-1, this strain could remove
      NO(3)(-)-N with 90% reduction of NO(3)(-)-N, corresponding to oxidizing Fe-1 with
      71% oxidation of Fe-1 after 7 days of incubation. The result of kinetic
      evaluation indicated that this bacterium showed significant substrate affinity to
      both NO(3)(-)-N and Fe-1.

PMID- 25860713
TI  - Pilot-scale study of vertical flow constructed wetland combined with trickling
      filter and ferric chloride coagulation: influence of irregular operational
      conditions.
AB  - The aim of this study was to characterize the efficiency of an intensified
      process of vertical flow constructed wetland having the following
      particularities: (i) biological pretreatment by trickling filter, (ii) FeCl3
      injection for dissolved phosphorus removal and (iii) succession of different
      levels of redox conditions along the process line. A pilot-scale set-up designed
      to simulate a real-scale plant was constructed and operated using real
      wastewater. The influences of FeCl3 injection and water saturation level within
      the vertical flow constructed wetland stage on treatment performances were
      studied. Three different water saturation levels were compared by monitoring:
      suspended solids (SS), total phosphorus (TP), dissolved chemical oxygen demand
      (COD), ammonium, nitrate, phosphate, iron, and manganese. The results confirmed
      the good overall efficiency of the process and the contribution of the trickling
      filter pretreatment to COD removal and nitrification. The effects of water
      saturation level and FeCl3 injection on phosphorus removal were evaluated by
      analysis of the correlations between the variables. Under unsaturated conditions,
      good nitrification and no denitrification were observed. Under partly saturated
      conditions, both nitrification and denitrification were obtained, along with a
      good retention of SSs. Finally, under saturated conditions, the performance was
      decreased for almost all parameters. 

PMID- 25860714
TI  - The combination of coagulation, acid cracking and Fenton-like processes for olive
      oil mill wastewater treatment: phytotoxicity reduction and biodegradability
      augmentation.
AB  - Olive oil mill wastewater (OOMW) is one of the most important industrial
      wastewaters in the world due to high organic load and phenolic compounds. In this
      study, an integration of three processes including coagulation, acid cracking and
      Fenton-like was evaluated to treat OOMW. The performance of alum, ferric chloride
      and polyaluminum chloride was studied as coagulants. Among coagulants, ferric
      chloride showed the best results in comparison with the others. Coagulation
      process with FeCl3 removed 91.2% chemical oxygen demand (COD), 91.3% phenol,
      98.9% total suspended solids and 99.2% turbidity at condition of pH = 6 and 3,000
      mg/L coagulant dosage. Acid cracking process following the coagulation process
      with ferric chloride could slightly degrade organic compounds and provided
      suitable condition for the next process. Fenton-like process with zero valent
      iron (ZVI) was applied after coagulation and acid cracking. The optimal removal
      efficiency was achieved by Fenton-like process which was accomplished in
      condition of 7 g/L ZVI, 1,000 mg/L H2O2 and 180 min reaction time. The
      biodegradability of final effluent of this integration was improved significantly
      and biochemical oxygen demand5/COD value increased from 0.14 to 0.83. The results
      of germination tests revealed that phytotoxicity of the final effluent decreased.

PMID- 25860715
TI  - Optimization for extracellular polymeric substances extraction of microbial
      aggregates.
AB  - The extracellular polymeric substances (EPS) are important macromolecular
      components in microbial aggregates. The three EPS extraction methods - ultrasound
      + cation exchange resins (CER) + sulfide, ultrasound + formamide + NaOH, and
      ultrasound + heat - were investigated in the study, and the component differences
      of extracted EPS from the loose flocs and dense aerobic granules were compared
      using chemical analysis and three-dimensional excitation-emission matrix (3D
      EEM). Results showed that the contents of EPS were extracted effectively by
      ultrasound + formamide + NaOH and ultrasound + heat methods, and the ultrasound +
      CER + sulfide method did not extract the polysaccharides (PS) or protein (PN)
      contents from the sludge samples. The 3D-EEM analysis indicated that the nature
      of peak B/D, peak C/E/F, and peak A/G were attributed to PN-like, humic acid-like
      and fulvic acid-like fluorophores. All fluorophores can be detected from the EPS
      extracted through the ultrasound + heat method. Hopefully this will provide more
      information about the EPS interaction mechanism of microbial aggregates. 

PMID- 25860716
TI  - Acute toxicity of runoff from sealcoated pavement to Ceriodaphnia dubia and
      Pimephales promelas.
AB  - Runoff from coal-tar-based (CT) sealcoated pavement is a source of polycyclic
      aromatic hydrocarbons (PAHs) and N-heterocycles to surface waters. We
      investigated acute toxicity of simulated runoff collected from 5 h to 111 days
      after application of CT sealcoat and from 4 h to 36 days after application of
      asphalt-based sealcoat containing about 7% CT sealcoat (AS/CT-blend).
      Ceriodaphnia dubia (cladocerans) and Pimephales promelas (fathead minnows) were
      exposed in the laboratory to undiluted and 1:10 diluted runoff for 48 h, then
      transferred to control water and exposed to 4 h of ultraviolet radiation (UVR).
      Mortality following exposure to undiluted runoff from unsealed asphalt pavement
      and UVR was <=10% in all treatments. Test organisms exposed to undiluted CT
      runoff samples collected during the 3 days (C. dubia) or 36 days (P. promelas)
      following sealcoat application experienced 100% mortality prior to UVR exposure;
      with UVR exposure, mortality was 100% for runoff collected across the entire
      sampling period. Phototoxic-equivalent PAH concentrations and mortality
      demonstrated an exposure-response relation. The results indicate that runoff
      remains acutely toxic for weeks to months after CT sealcoat application. 

PMID- 25860717
TI  - Grey water treatment by the slanted soil system with unsorted soil media.
AB  - This study evaluated the performance of unsorted soil media in the slanted soil
      treatment system, in terms of removal efficiency in suspended solids (SS),
      chemical oxygen demand (COD), linear alkylbenzene sulphonate (LAS) and
      Escherichia coli, and lifetime until clogging occurs. Unsorted soil performed
      longer lifetime until clogging than sorted fine soil. Removal of SS, COD, and LAS
      also performed same or better level in unsorted soil than fine soil. As reaction
      coefficients of COD and LAS were described as a function of the hydraulic loading
      rate, we can design a slanted soil system according to the expected hydraulic
      loading rate and the targeted level of COD or LAS in effluent. Regarding bacteria
      removal, unsorted soil performed sufficient reduction of E. coli for 5 weeks;
      however, the removal process occurred throughout all four chambers, while that of
      fine soil occurred in one to two chambers. 

PMID- 25860719
TI  - Angiotensin-converting enzyme for noninvasive assessment of liver fibrosis in
      autoimmune hepatitis.
AB  - BACKGROUND AND AIM: There are no validated noninvasive markers of liver fibrosis
      in autoimmune hepatitis (AIH). An activated renin-angiotensin system (RAS) and
      its key element angiotensin-converting enzyme (ACE) have been implicated in the
      pathogenesis of hepatic fibrogenesis. We aimed to study the assumed role of
      activated RAS in the fibrogenic process and whether the serum concentration of
      ACE can predict different fibrosis stages in AIH. PATIENTS AND METHODS: Serum
      samples of 73 consecutive patients who were diagnosed with AIH were analysed for
      ACE concentration. All patients underwent a liver biopsy. RESULTS: Serum ACE
      levels increased significantly for each fibrosis score. The median ACE was 45 U/l
      in patients with fibrosis score I, 54 U/l in patients with fibrosis score II, 68
      U/l in patients with fibrosis score III and 87 U/l in patients with fibrosis
      score IV. For significant fibrosis (<=F2), a 56 U/l cut-off value of ACE had
      95.5% sensitivity and 74.5% specificity, and receiver-operating characteristic
      curves showed an area under the curve (AUC) of 0.89. For advanced fibrosis
      (<=F3), a 64 U/l cut-off level of ACE had 85.2% sensitivity and 94.8%
      specificity, and AUC was 0.91. For cirrhosis, a 68 U/l cut-off level of ACE had
      100% sensitivity and 84.4% specificity, and AUC was 0.95. CONCLUSION: Our results
      suggest that activated RAS may sustain hepatic fibrogenesis in AIH. Measurement
      of serum ACE offers an easy, accurate and inexpensive noninvasive method that
      differentiates significant from nonsignificant liver fibrosis in AIH. Blockade of
      RAS may exert beneficial effects on fibrosis progression in AIH.

PMID- 25860718
TI  - Interleukin-1 receptor antagonist protects against lipopolysaccharide induced
      diaphragm weakness in preterm lambs.
AB  - Chorioamnionitis (inflammation of the fetal membranes) is strongly associated
      with preterm birth and in utero exposure to inflammation significantly impairs
      contractile function in the preterm lamb diaphragm. The fetal inflammatory
      response to intra-amniotic (IA) lipopolysaccharide (LPS) is orchestrated via
      interleukin 1 (IL-1). We aimed to determine if LPS induced contractile
      dysfunction in the preterm diaphragm is mediated via the IL-1 pathway. Pregnant
      ewes received IA injections of recombinant human IL-1 receptor antagonist (rhIL
      1ra) (Anakinra; 100 mg) or saline (Sal) 3 h prior to second IA injections of LPS
      (4 mg) or Sal at 119d gestational age (GA). Preterm lambs were killed after
      delivery at 121d GA (term = 150 d). Muscle fibres dissected from the right hemi
      diaphragm were mounted in an in vitro muscle test system for assessment of
      contractile function. The left hemi-diaphragm was snap frozen for molecular and
      biochemical analyses. Maximum specific force in lambs exposed to IA LPS (Sal/LPS
      group) was 25% lower than in control lambs (Sal/Sal group; p=0.025). LPS-induced
      diaphragm weakness was associated with higher plasma IL-6 protein, diaphragm IL
      1beta mRNA and oxidised glutathione levels. Pre-treatment with rhIL-1ra (rhIL
      1ra/LPS) ameliorated the LPS-induced diaphragm weakness and blocked systemic and
      local inflammatory responses, but did not prevent the rise in oxidised
      glutathione. These findings indicate that LPS induced diaphragm dysfunction is
      mediated via IL-1 and occurs independently of oxidative stress. Therefore, the IL
      1 pathway represents a potential therapeutic target in the management of impaired
      diaphragm function in preterm infants. 

PMID- 25860720
TI  - Improving diagnostic yield in obscure gastrointestinal bleeding--how virtual
      chromoendoscopy may be the answer.
AB  - BACKGROUND AND AIM: A significant proportion of patients presenting with obscure
      gastrointestinal bleeding (OGIB) have negative small bowel capsule endoscopy
      (SBCE) examinations, and yet remain at risk of rebleeding. We aimed to evaluate
      whether a second-look review of SBCE images using flexible spectral color
      enhancement (FICE) may improve the detection of potentially bleeding lesions.
      MATERIALS AND METHODS: This was a retrospective, single-center study including
      consecutive patients with OGIB subjected to SBCE, whose standard white light
      examination was nondiagnostic. Each SBCE was reviewed using FICE 1. New findings
      were labeled as either P1 or P2 lesions according to bleeding potential. Patients
      were followed up to assess the incidence of rebleeding. RESULTS: A total of 42
      consecutive patients were included. Sixteen patients (38%) experienced rebleeding
      after a mean follow-up of 26 months. Review of SBCE images using FICE 1 enabled
      the identification of previously unrecognized P2 lesions, mainly angioectasias,
      in nine patients (21%) and P1 lesions, mainly erosions, in 26 patients (62%).
      Among patients who experienced rebleeding, 13/16 (81%) were diagnosed with P1
      lesions with FICE 1 (P=0.043), whereas 3/16 (19%) had confirmed nondiagnostic
      SBCE and only 1/16 (6%) had newly diagnosed P2 (plus P1) lesions. An alternative
      source of bleeding outside the small bowel was found in only 3/16 (19%) patients
      with rebleeding during the follow-up. CONCLUSION: In a significant proportion of
      patients with OGIB, FICE 1 may detect potentially bleeding lesions previously
      missed under conventional white light SBCE. Review of nondiagnostic SBCE with
      FICE 1 may be a valuable strategy to obviate the need for further investigations
      in patients with OGIB, particularly for those who experience rebleeding.

PMID- 25860722
TI  - Editorial: lighting up research.

PMID- 25860721
TI  - Uncommon Implantation Sites of Ectopic Pregnancy: Thinking beyond the Complex
      Adnexal Mass.
AB  - Ectopic pregnancy occurs when implantation of the blastocyst takes place in a
      site other than the endometrium of the uterine cavity. Uncommon implantation
      sites of ectopic pregnancy include the cervix, interstitial segment of the
      fallopian tube, scar from a prior cesarean delivery, uterine myometrium, ovary,
      and peritoneal cavity. Heterotopic and twin ectopic pregnancies are other rare
      manifestations. Ultrasonography (US) plays a central role in diagnosis of
      uncommon ectopic pregnancies. US features of an interstitial ectopic pregnancy
      include an echogenic interstitial line and abnormal bulging of the myometrial
      contour. A gestational sac that is located below the internal os of the cervix
      and that contains an embryo with a fetal heartbeat is indicative of a cervical
      ectopic pregnancy. In a cesarean scar ectopic pregnancy, the gestational sac is
      implanted in the anterior lower uterine segment at the site of the cesarean scar,
      with thinning of the myometrium seen anterior to the gestational sac. An
      intramural gestational sac implants in the uterine myometrium, separate from the
      uterine cavity and fallopian tubes. In an ovarian ectopic pregnancy, a
      gestational sac with a thick hyperechoic circumferential rim is located in or on
      the ovarian parenchyma. An intraperitoneal gestational sac is present in an
      abdominal ectopic pregnancy. Intra- and extrauterine gestational sacs are seen in
      a heterotopic pregnancy. Two adnexal heartbeats suggest a live twin ectopic
      pregnancy. Recognition of the specific US features will help radiologists
      diagnose these uncommon types of ectopic pregnancy.

PMID- 25860723
TI  - Local hidden variable models for entangled quantum States using finite shared
      randomness.
AB  - The statistics of local measurements performed on certain entangled states can be
      reproduced using a local hidden variable (LHV) model. While all known models make
      use of an infinite amount of shared randomness, we show that essentially all
      entangled states admitting a LHV model can be simulated with finite shared
      randomness. Our most economical model simulates noisy two-qubit Werner states
      using only log_{2}(12)?3.58 bits of shared randomness. We also discuss the case
      of positive operator valued measures, and the simulation of nonlocal states with
      finite shared randomness and finite communication. Our work represents a first
      step towards quantifying the cost of LHV models for entangled quantum states. 

PMID- 25860724
TI  - Macroscopic quantum state analyzed particle by particle.
AB  - Macroscopic quantum phenomena, e.g., superconductivity and squeezing, are
      believed to result from entanglement of macroscopic numbers of particles. We
      report the first direct study of this kind of entanglement: we use discrete
      quantum tomography to reconstruct the joint quantum state of photon pairs
      extracted from polarization-squeezed light. Our observations confirm several
      predictions from spin-squeezing theory [Beduini et al., Phys. Rev. Lett. 111,
      143601 (2013)], including strong entanglement and entanglement of all photon
      pairs within the squeezing coherence time. This photon-by-photon analysis may
      give insight into other macroscopic many-body systems, e.g., photon Bose-Einstein
      condensates. 

PMID- 25860725
TI  - Improving the coherence time of a quantum system via a coupling to a short-lived
      system.
AB  - In this Letter, we propose a counterintuitive use of a hybrid system where the
      coherence time of a quantum system can be significantly improved by coupling it
      with a system of a shorter coherence time. Coupling a two-level system with a
      single nitrogen-vacancy (NV^{-}) center, a dark state of the NV^{-} center
      naturally forms after the hybridization. We show that this dark state becomes
      robust against noise due to the coupling even when the coherence time of the two
      level system is much shorter than that of the NV^{-} center. Our proposal opens a
      new way to use a quantum hybrid system for the realization of robust quantum
      information processing. 

PMID- 25860726
TI  - Phase-modulated decoupling and error suppression in qubit-oscillator systems.
AB  - We present a scheme designed to suppress the dominant source of infidelity in
      entangling gates between quantum systems coupled through intermediate bosonic
      oscillator modes. Such systems are particularly susceptible to residual qubit
      oscillator entanglement at the conclusion of a gate period that reduces the
      fidelity of the target entangling operation. We demonstrate how the exclusive use
      of discrete shifts in the phase of the field moderating the qubit-oscillator
      interaction is sufficient to both ensure multiple oscillator modes are decoupled
      and to suppress the effects of fluctuations in the driving field. This approach
      is amenable to a wide variety of technical implementations including geometric
      phase gates in superconducting qubits and the Molmer-Sorensen gate for trapped
      ions. We present detailed example protocols tailored to trapped-ion experiments
      and demonstrate that our approach has the potential to enable multiqubit gate
      implementation with a significant reduction in technical complexity relative to
      previously demonstrated protocols. 

PMID- 25860727
TI  - Deterministic superreplication of one-parameter unitary transformations.
AB  - We show that one can deterministically generate, out of N copies of an unknown
      unitary operation, up to N^{2} almost perfect copies. The result holds for all
      operations generated by a Hamiltonian with an unknown interaction strength. This
      generalizes a similar result in the context of phase-covariant cloning where,
      however, superreplication comes at the price of an exponentially reduced
      probability of success. We also show that multiple copies of unitary operations
      can be emulated by operations acting on a much smaller space, e.g., a magnetic
      field acting on a single n-level system allows one to emulate the action of the
      field on n^{2} qubits. 

PMID- 25860728
TI  - Universal superreplication of unitary gates.
AB  - Quantum states obey an asymptotic no-cloning theorem, stating that no
      deterministic machine can reliably replicate generic sequences of identically
      prepared pure states. In stark contrast, we show that generic sequences of
      unitary gates can be replicated deterministically at nearly quadratic rates, with
      an error vanishing on most inputs except for an exponentially small fraction. The
      result is not in contradiction with the no-cloning theorem, since the
      impossibility of deterministically transforming pure states into unitary gates
      prevents the application of the gate replication protocol to states. In addition
      to gate replication, we show that N parallel uses of a completely unknown unitary
      gate can be compressed into a single gate acting on O(log_{2}N) qubits, leading
      to an exponential reduction of the amount of quantum communication needed to
      implement the gate remotely. 

PMID- 25860730
TI  - Resource quality of a symmetry-protected topologically ordered phase for quantum
      computation.
AB  - We investigate entanglement naturally present in the 1D topologically ordered
      phase protected with the on-site symmetry group of an octahedron as a potential
      resource for teleportation-based quantum computation. We show that, as long as
      certain characteristic lengths are finite, all its ground states have the
      capability to implement any unit-fidelity one-qubit gate operation asymptotically
      as a key computational building block. This feature is intrinsic to the entire
      phase, in that perfect gate fidelity coincides with perfect string order
      parameters under a state-insensitive renormalization procedure. Our approach may
      pave the way toward a novel program to classify quantum many-body systems based
      on their operational use for quantum information processing. 

PMID- 25860729
TI  - Experimental implementation of a quantum optical state comparison amplifier.
AB  - We present an experimental demonstration of a practical nondeterministic quantum
      optical amplification scheme that employs two mature technologies, state
      comparison and photon subtraction, to achieve amplification of known sets of
      coherent states with high fidelity. The amplifier uses coherent states as a
      resource rather than single photons, which allows for a relatively simple light
      source, such as a diode laser, providing an increased rate of amplification. The
      amplifier is not restricted to low amplitude states. With respect to the two key
      parameters, fidelity and the amplified state production rate, we demonstrate
      significant improvements over previous experimental implementations, without the
      requirement of complex photonic components. Such a system may form the basis of
      trusted quantum repeaters in nonentanglement-based quantum communications systems
      with known phase alphabets, such as quantum key distribution or quantum digital
      signatures. 

PMID- 25860731
TI  - Adiabatic processes realized with a trapped Brownian particle.
AB  - The ability to implement adiabatic processes in the mesoscale is of key
      importance in the study of artificial or biological micro- and nanoengines.
      Microadiabatic processes have been elusive to experimental implementation due to
      the difficulty in isolating Brownian particles from their fluctuating
      environment. Here we report on the experimental realization of a microscopic
      quasistatic adiabatic process employing a trapped Brownian particle. We
      circumvent the complete isolation of the Brownian particle by designing a
      protocol where both characteristic volume and temperature of the system are
      changed in such a way that the entropy of the system is conserved along the
      process. We compare the protocols that follow from either the overdamped or
      underdamped descriptions, demonstrating that the latter is mandatory in order to
      obtain a vanishing average heat flux to the particle. We provide analytical
      expressions for the distributions of the fluctuating heat and entropy and verify
      them experimentally. Our protocols could serve to implement the first microscopic
      engine that is able to attain the fundamental limit for the efficiency set by
      Carnot. 

PMID- 25860732
TI  - R^{3} index for four-dimensional (N)=2 field theories.
AB  - In theories with N=2 supersymmetry on R^{3,1}, supersymmetric bound states can
      decay across walls of marginal stability in the space of Coulomb branch
      parameters, leading to discontinuities in the BPS indices Omega(gamma,u). We
      consider a supersymmetric index I which receives contributions from 1/2-BPS
      states, generalizing the familiar Witten index Tr(-1)^{F}e^{-betaH}. We expect I
      to be smooth away from loci where massless particles appear, thanks to
      contributions from the continuum of multiparticle states. Taking inspiration from
      a similar phenomenon in the hypermultiplet moduli space of N=2 string vacua, we
      conjecture a formula expressing I in terms of the BPS indices Omega(gamma,u),
      which is continuous across the walls and exhibits the expected contributions from
      single particle states at large beta. This gives a universal prediction for the
      contributions of multiparticle states to the index I. This index is naturally a
      function on the moduli space after reduction on a circle, closely related to the
      canonical hyperkahler metric and hyperholomorphic connection on this space. 

PMID- 25860733
TI  - Supersymmetric Ruijsenaars-Schneider model.
AB  - An integrable supersymmetric generalization of the trigonometric Ruijsenaars
      Schneider model is presented whose symmetry algebra includes the super Poincare
      algebra. Moreover, its Hamiltonian is shown to be diagonalized by the recently
      introduced Macdonald superpolynomials. Somewhat surprisingly, the consistency of
      the scalar product forces the discreteness of the Hilbert space. 

PMID- 25860735
TI  - (d-)-(u-) asymmetry in the proton in chiral effective theory.
AB  - We compute the d[over -]-u[over -] asymmetry in the proton in chiral effective
      theory, including both nucleon and Delta degrees of freedom, within the
      relativistic and heavy baryon frameworks. In addition to the distribution at x>0,
      we compute the corrections to the asymmetry from zero momentum contributions from
      pion rainbow and bubble diagrams at x=0, which have not been accounted for in
      previous analyses. We find that the empirical x dependence of d[over -]-u[over -]
      as well as the integrated asymmetry can be well reproduced in terms of a
      transverse momentum cutoff parameter. 

PMID- 25860736
TI  - Uncertainty quantification for nuclear density functional theory and information
      content of new measurements.
AB  - Statistical tools of uncertainty quantification can be used to assess the
      information content of measured observables with respect to present-day
      theoretical models, to estimate model errors and thereby improve predictive
      capability, to extrapolate beyond the regions reached by experiment, and to
      provide meaningful input to applications and planned measurements. To showcase
      new opportunities offered by such tools, we make a rigorous analysis of
      theoretical statistical uncertainties in nuclear density functional theory using
      Bayesian inference methods. By considering the recent mass measurements from the
      Canadian Penning Trap at Argonne National Laboratory, we demonstrate how the
      Bayesian analysis and a direct least-squares optimization, combined with high
      performance computing, can be used to assess the information content of the new
      data with respect to a model based on the Skyrme energy density functional
      approach. Employing the posterior probability distribution computed with a
      Gaussian process emulator, we apply the Bayesian framework to propagate
      theoretical statistical uncertainties in predictions of nuclear masses, two
      neutron dripline, and fission barriers. Overall, we find that the new mass
      measurements do not impose a constraint that is strong enough to lead to
      significant changes in the model parameters. The example discussed in this study
      sets the stage for quantifying and maximizing the impact of new measurements with
      respect to current modeling and guiding future experimental efforts, thus
      enhancing the experiment-theory cycle in the scientific method. 

PMID- 25860738
TI  - Efficient autoionization following intense laser-cluster interactions.
AB  - Electron emission as a result of the interaction of clusters with intense laser
      pulses is commonly understood in terms of direct and evaporative ionization
      processes. In contrast, we provide evidence here of an important role played by
      autoionization in intense field ionization of molecular oxygen clusters.
      Superexcited states are populated during the cluster expansion, and their
      autoionization is observed on a ns time scale. Decay processes on fs to ps time
      scales are obscured by energy exchange of the emitted electrons with the
      environment. 

PMID- 25860739
TI  - Strong-field excitation of helium: bound state distribution and spin effects.
AB  - Using field ionization combined with the direct detection of excited neutral
      atoms we measured the distribution of principal quantum number n of excited He
      Rydberg states after strong-field excitation at laser intensities well in the
      tunneling regime. Our results confirm theoretical predictions from semiclassical
      and quantum mechanical calculations and simultaneously underpin the validity of
      the semiclassical frustrated tunneling ionization model. Moreover, since our
      experimental detection scheme is spin sensitive in the case of He atoms, we show
      that strong-field excitation leads to strong population of triplet states. The
      origin of it lies in the fact that high angular momentum states are accessible in
      strong-field excitation. Thus, singlet-triplet transitions become possible due to
      the increased importance of spin-orbit interaction rather than due to direct
      laser induced spin-flip processes. 

PMID- 25860737
TI  - Direct photonic coupling of a semiconductor quantum dot and a trapped ion.
AB  - Coupling individual quantum systems lies at the heart of building scalable
      quantum networks. Here, we report the first direct photonic coupling between a
      semiconductor quantum dot and a trapped ion and we demonstrate that single
      photons generated by a quantum dot controllably change the internal state of a
      Yb^{+} ion. We ameliorate the effect of the 60-fold mismatch of the radiative
      linewidths with coherent photon generation and a high-finesse fiber-based optical
      cavity enhancing the coupling between the single photon and the ion. The transfer
      of information presented here via the classical correlations between the
      sigma_{z} projection of the quantum-dot spin and the internal state of the ion
      provides a promising step towards quantum-state transfer in a hybrid photonic
      network. 

PMID- 25860741
TI  - Quantum simulation of energy transport with embedded Rydberg aggregates.
AB  - We show that an array of ultracold Rydberg atoms embedded in a laser driven
      background gas can serve as an aggregate for simulating exciton dynamics and
      energy transport with a controlled environment. Energetic disorder and
      decoherence introduced by the interaction with the background gas atoms can be
      controlled by the laser parameters. This allows for an almost ideal realization
      of a Haken-Reineker-Strobl-type model for energy transport. The transport can be
      monitored using the same mechanism that provides control over the environment.
      The degree of decoherence is traced back to information gained on the excitation
      location through the monitoring, turning the setup into an experimentally
      accessible model system for studying the effects of quantum measurements on the
      dynamics of a many-body quantum system. 

PMID- 25860740
TI  - Coherent electronic wave packet motion in C(60) controlled by the waveform and
      polarization of few-cycle laser fields.
AB  - Strong laser fields can be used to trigger an ultrafast molecular response that
      involves electronic excitation and ionization dynamics. Here, we report on the
      experimental control of the spatial localization of the electronic excitation in
      the C_{60} fullerene exerted by an intense few-cycle (4 fs) pulse at 720 nm. The
      control is achieved by tailoring the carrier-envelope phase and the polarization
      of the laser pulse. We find that the maxima and minima of the photoemission
      asymmetry parameter along the laser-polarization axis are synchronized with the
      localization of the coherent electronic wave packet at around the time of
      ionization. 

PMID- 25860742
TI  - Nonequilibrium phase transition of interacting bosons in an intra-cavity optical
      lattice.
AB  - We investigate the nonlinear light-matter interaction of a Bose-Einstein
      condensate trapped in an external periodic potential inside an optical cavity
      which is weakly coupled to vacuum radiation modes and driven by a transverse pump
      field. Based on a generalized Bose-Hubbard model which incorporates a single
      cavity mode, we include the collective backaction of the atoms on the cavity
      light field and determine the nonequilibrium quantum phases within the
      nonperturbative bosonic dynamical mean-field theory. With the system parameters
      adapted to recent experiments, we find a quantum phase transition from a normal
      phase to a self-organized superfluid phase, which is related to the Hepp-Lieb
      Dicke superradiance phase transition. For even stronger pumping, a self-organized
      Mott insulator phase arises. 

PMID- 25860743
TI  - Cavity cooling a single charged levitated nanosphere.
AB  - Optomechanical cavity cooling of levitated objects offers the possibility for
      laboratory investigation of the macroscopic quantum behavior of systems that are
      largely decoupled from their environment. However, experimental progress has been
      hindered by particle loss mechanisms, which have prevented levitation and cavity
      cooling in a vacuum. We overcome this problem with a new type of hybrid electro
      optical trap formed from a Paul trap within a single-mode optical cavity. We
      demonstrate a factor of 100 cavity cooling of 400 nm diameter silica spheres
      trapped in vacuum. This paves the way for ground-state cooling in a smaller,
      higher finesse cavity, as we show that a novel feature of the hybrid trap is that
      the optomechanical cooling becomes actively driven by the Paul trap, even for
      singly charged nanospheres. 

PMID- 25860744
TI  - Spatially dependent electromagnetically induced transparency.
AB  - Recent years have seen vast progress in the generation and detection of
      structured light, with potential applications in high capacity optical data
      storage and continuous variable quantum technologies. Here we measure the
      transmission of structured light through cold rubidium atoms and observe regions
      of electromagnetically induced transparency (EIT), using the phase profile as
      control parameter for the atomic opacity. With q plates we generate a probe beam
      with azimuthally varying phase and polarization structure, and its right and left
      circular polarization components provide the probe and control of an EIT
      transition. We observe an azimuthal modulation of the absorption profile that is
      dictated by the phase and polarization structure of the probe laser. Conventional
      EIT systems do not exhibit phase sensitivity. We show, however, that a weak
      transverse magnetic field closes the EIT transitions, thereby generating phase
      dependent dark states which in turn lead to phase-dependent transparency, in
      agreement with our measurements. 

PMID- 25860745
TI  - Subwavelength topological edge States in optically resonant dielectric
      structures.
AB  - We suggest a novel type of photonic topological edge states in zigzag arrays of
      dielectric nanoparticles based on optically induced magnetic Mie resonances. We
      verify our general concept by the proof-of-principle microwave experiments with
      dielectric spherical particles, and demonstrate, experimentally, the ability to
      control the subwavelength topologically protected electromagnetic edge modes by
      changing the polarization of the incident wave. 

PMID- 25860746
TI  - Consistency properties of a chaotic semiconductor laser driven by optical
      feedback.
AB  - We experimentally study consistency properties of a semiconductor laser in
      response to a coherent optical drive originating from delayed feedback. The laser
      is connected to a short and a long optical fiber loop, switched such that only
      one is providing input to the laser at a time. This way, repeating the exact same
      optical drive twice, we find consistent or inconsistent responses depending on
      the pump parameter and we relate the kind of response to strong and weak chaos.
      Moreover, we are able to experimentally determine the sub-Lyapunov exponent,
      underlying the consistency properties. 

PMID- 25860747
TI  - Coulomb-driven energy boost of heavy ions for laser-plasma acceleration.
AB  - An unprecedented increase of kinetic energy of laser accelerated heavy ions is
      demonstrated. Ultrathin gold foils have been irradiated by an ultrashort laser
      pulse at a peak intensity of 8*10^{19}  W/  cm^{2}. Highly charged gold ions with
      kinetic energies up to >200  MeV and a bandwidth limited energy distribution have
      been reached by using 1.3 J laser energy on target. 1D and 2D particle in cell
      simulations show how a spatial dependence on the ion's ionization leads to an
      enhancement of the accelerating electrical field. Our theoretical model considers
      a spatial distribution of the ionization inside the thin target, leading to a
      field enhancement for the heavy ions by Coulomb explosion. It is capable of
      explaining the energy boost of highly charged ions, enabling a higher efficiency
      for the laser-driven heavy ion acceleration. 

PMID- 25860748
TI  - Multibeam seeded brillouin sidescatter in inertial confinement fusion
      experiments.
AB  - We present the first observations of multibeam weakly seeded Brillouin
      sidescatter in indirect-drive inertial confinement fusion (ICF) experiments. Two
      seeding mechanisms have been identified and quantified: specular reflections
      ("glint") from opposite hemisphere beams, and Brillouin backscatter from
      neighboring beams with a different angle of incidence. Seeded sidescatter can
      dominate the overall coupling losses, so understanding this process is crucial
      for proper accounting of energy deposition and drive symmetry. Glint-seeded
      scattered light could also be used to probe hydrodynamic conditions inside ICF
      targets. 

PMID- 25860749
TI  - Strong ionization asymmetry in a geometrically symmetric radio frequency
      capacitively coupled plasma induced by sawtooth voltage waveforms.
AB  - The ionization dynamics in geometrically symmetric parallel plate capacitively
      coupled plasmas driven by radio frequency tailored voltage waveforms is
      investigated using phase resolved optical emission spectroscopy (PROES) and
      particle-in-cell (PIC) simulations. Temporally asymmetric waveforms induce
      spatial asymmetries and offer control of the spatiotemporal dynamics of electron
      heating and associated ionization structures. Sawtooth waveforms with different
      rise and fall rates are employed using truncated Fourier series approximations of
      an ideal sawtooth. Experimental PROES results obtained in argon plasmas are
      compared with PIC simulations, showing excellent agreement. With waveforms
      comprising a fast voltage drop followed by a slower rise, the faster sheath
      expansion in front of the powered electrode causes strongly enhanced ionization
      in this region. The complementary waveform causes an analogous effect in front of
      the grounded electrode. 

PMID- 25860750
TI  - Decrease of atmospheric neutron counts observed during thunderstorms.
AB  - We report here, in brief, some results of the observation and analysis of
      sporadic variations of atmospheric thermal neutron flux during thunderstorms. The
      results obtained with unshielded scintillation neutron detectors show a prominent
      flux decrease correlated with meteorological precipitations after a long dry
      period. No observations of neutron production during thunderstorms were reported
      during the three-year period of data recording. 

PMID- 25860751
TI  - Electron kinetics inferred from observations of microwave bursts during edge
      localized modes in the mega-amp spherical tokamak.
AB  - Recent measurements of microwave and x-ray emission during edge localized mode
      (ELM) activity in tokamak plasmas provide a fresh perspective on ELM physics. It
      is evident that electron kinetics, which are not incorporated in standard (fluid)
      models for the instability that drives ELMs, play a key role in the new
      observations. These effects should be included in future models for ELMs and the
      ELM cycle. The observed radiative effects paradoxically imply acceleration of
      electrons parallel to the magnetic field combined with rapid acquisition of
      perpendicular momentum. It is shown that this paradox can be resolved by the
      action of the anomalous Doppler instability which enables fast collective
      radiative relaxation, in the perpendicular direction, of electrons accelerated in
      the parallel direction by inductive electric fields generated by the initial ELM
      instability. 

PMID- 25860752
TI  - Tunable spin-orbit coupling via strong driving in ultracold-atom systems.
AB  - Spin-orbit coupling is an essential ingredient in topological materials,
      conventional and quantum-gas-based alike. Engineered spin-orbit coupling in
      ultracold-atom systems-unique in their experimental control and measurement
      opportunities-provides a major opportunity to investigate and understand
      topological phenomena. Here we experimentally demonstrate and theoretically
      analyze a technique for controlling spin-orbit coupling in a two-component Bose
      Einstein condensate using amplitude-modulated Raman coupling. 

PMID- 25860753
TI  - Sudden expansion of a one-dimensional bose gas from power-law traps.
AB  - We analyze free expansion of a trapped one-dimensional Bose gas after a sudden
      release from the confining trap potential. By using the stationary phase and
      local density approximations, we show that the long-time asymptotic density
      profile and the momentum distribution of the gas are determined by the initial
      distribution of Bethe rapidities (quasimomenta) and hence can be obtained from
      the solutions to the Lieb-Liniger equations in the thermodynamic limit. For
      expansion from a harmonic trap, and in the limits of very weak and very strong
      interactions, we recover the self-similar scaling solutions known from the
      hydrodynamic approach. For all other power-law traps and arbitrary interaction
      strengths, the expansion is not self-similar and shows strong dependence of the
      density profile evolution on the trap anharmonicity. We also characterize
      dynamical fermionization of the expanding cloud in terms of correlation functions
      describing phase and density fluctuations. 

PMID- 25860754
TI  - Spontaneous quantum Hall effect in an atomic spinor Bose-Fermi mixture.
AB  - We study a mixture of spin-1 bosonic and spin-1/2 fermionic cold atoms, e.g.,
      ^{87}Rb and ^{6}Li, confined in a triangular optical lattice. With fermions at
      3/4 filling, Fermi surface nesting leads to spontaneous formation of various spin
      textures of bosons in the ground state, such as collinear, coplanar, and even
      noncoplanar spin orders. The phase diagram is mapped out with varying boson
      tunneling and Bose-Fermi interactions. Most significantly, in one noncoplanar
      state the mixture is found to exhibit a spontaneous quantum Hall effect in
      fermions and crystalline superfluidity in bosons, both driven by interaction. 

PMID- 25860755
TI  - Bose-Einstein condensation of magnons in atomic hydrogen gas.
AB  - We report on experimental observation of Bose-Einstein condensation (BEC)-like
      behavior of quantized electron spin waves (magnons) in a dense gas of spin
      polarized atomic hydrogen. The magnons are trapped and controlled with
      inhomogeneous magnetic fields and described by a Schrodinger-like wave equation,
      in analogy to the BEC experiments with neutral atoms. We have observed the
      appearance of a sharp feature in the ESR spectrum displaced from the normal spin
      wave spectrum. We believe that this observation corresponds to a sudden growth of
      the ground-state population of the magnons and emergence of their spontaneous
      coherence for hydrogen gas densities exceeding a critical value, dependent on the
      trapping potential. We interpret the results as a BEC of nonequilibrium magnons
      which were formed by applying the rf power. 

PMID- 25860756
TI  - Metallic icosahedron phase of sodium at terapascal pressures.
AB  - Alkali metals exhibit unexpected structures and electronic behavior at high
      pressures. Compression of metallic sodium (Na) to 200 GPa leads to the stability
      of a wide-band-gap insulator with the double hexagonal hP4 structure. Post-hP4
      structures remain unexplored, but they are important for addressing the question
      of the pressure at which Na reverts to a metal. Here, we report the reentrant
      metallicity of Na at the very high pressure of 15.5 terapascal (TPa), predicted
      using first-principles structure searching simulations. Na is therefore
      insulating over the large pressure range of 0.2-15.5 TPa. Unusually, Na adopts an
      oP8 structure at pressures of 117-125 GPa and the same oP8 structure at 1.75-15.5
      TPa. The metallization of Na occurs on the formation of a stable and striking
      body-centered cubic cI24 electride structure consisting of Na_{12} icosahedra,
      each housing at its center about one electron that is not associated with any Na
      ions. 

PMID- 25860757
TI  - Rigidity transition in materials: hardness is driven by weak atomic constraints.
AB  - Understanding the composition dependence of the hardness in materials is of
      primary importance for infrastructures and handled devices. Stimulated by the
      need for stronger protective screens, topological constraint theory has recently
      been used to predict the hardness in glasses. Herein, we report that the concept
      of rigidity transition can be extended to a broader range of materials than just
      glass. We show that hardness depends linearly on the number of angular
      constraints, which, compared to radial interactions, constitute the weaker ones
      acting between the atoms. This leads to a predictive model for hardness,
      generally applicable to any crystalline or glassy material. 

PMID- 25860758
TI  - Phonon-pump extreme-ultraviolet-photoemission probe in graphene: anomalous
      heating of Dirac carriers by lattice deformation.
AB  - We modulate the atomic structure of bilayer graphene by driving its lattice at
      resonance with the in-plane E_{1u} lattice vibration at 6.3  MUm. Using time- and
      angle-resolved photoemission spectroscopy (tr-ARPES) with extreme-ultraviolet
      (XUV) pulses, we measure the response of the Dirac electrons near the K point. We
      observe that lattice modulation causes anomalous carrier dynamics, with the Dirac
      electrons reaching lower peak temperatures and relaxing at faster rate compared
      to when the excitation is applied away from the phonon resonance or in monolayer
      samples. Frozen phonon calculations predict dramatic band structure changes when
      the E_{1u} vibration is driven, which we use to explain the anomalous dynamics
      observed in the experiment. 

PMID- 25860759
TI  - Jamming criticality revealed by removing localized buckling excitations.
AB  - Recent theoretical advances offer an exact, first-principles theory of jamming
      criticality in infinite dimension as well as universal scaling relations between
      critical exponents in all dimensions. For packings of frictionless spheres near
      the jamming transition, these advances predict that nontrivial power-law
      exponents characterize the critical distribution of (i) small interparticle gaps
      and (ii) weak contact forces, both of which are crucial for mechanical stability.
      The scaling of the interparticle gaps is known to be constant in all spatial
      dimensions d-including the physically relevant d=2 and 3, but the value of the
      weak force exponent remains the object of debate and confusion. Here, we resolve
      this ambiguity by numerical simulations. We construct isostatic jammed packings
      with extremely high accuracy, and introduce a simple criterion to separate the
      contribution of particles that give rise to localized buckling excitations, i.e.,
      bucklers, from the others. This analysis reveals the remarkable dimensional
      robustness of mean-field marginality and its associated criticality. 

PMID- 25860760
TI  - Ordered and reversible hydrogenation of silicene.
AB  - The hydrogenation of monatomic silicene sheet on Ag(111) was studied by scanning
      tunneling microscopy and density functional theory calculations. It was observed
      that hydrogenation of silicene at room temperature results in a perfectly ordered
      gamma-(3*3) superstructure. A theoretical model, which involves seven H atoms and
      rearranged buckling of Si atoms, was proposed and agrees with experiments very
      well. Moreover, by annealing to a moderate temperature, about 450 K, a
      dehydrogenation process occurs and the clean silicene surface can be fully
      recovered. Such uniformly ordered and reversible hydrogenation may be useful for
      tuning the properties of silicene as well as for controllable hydrogen storage. 

PMID- 25860761
TI  - Kondo interactions from band reconstruction in YbInCu(4).
AB  - We combine resonant inelastic x-ray scattering and model calculations in the
      Kondo lattice compound YbInCu_{4}, a system characterized by a dramatic increase
      in Kondo temperature and associated valence fluctuations below a first-order
      valence transition at T?42  K. The bulk-sensitive, element-specific, and valence
      projected charge excitation spectra reveal an unusual quasigap in the Yb-derived
      state density which drives an instability of the electronic structure and
      renormalizes the low-energy effective Hamiltonian at the transition. Our results
      provide long-sought experimental evidence for a link between temperature-driven
      changes in the low-energy Kondo scale and the higher-energy electronic structure
      of this system. 

PMID- 25860763
TI  - Spin pumping in the presence of spin-orbit coupling.
AB  - Spin pumping and related phenomena have been observed recently in heavy metals
      and topological insulators, where the spin-orbit coupling plays an essential
      role. We have developed a spin-pumping formalism that explicitly includes the
      spin-orbit coupling at interfaces and disorder in the layers. Spin pumping across
      an interface with spin-orbit coupling and the attendant backflow are treated on
      an equal footing. We resolve some long-standing issues on the conflicting
      conclusions about the spin-diffusion length for Pt, and the origin of spin-memory
      loss at interfaces with heavy metals. In addition, we predict some heretofore
      unanticipated spin-pumping phenomena. 

PMID- 25860762
TI  - Revealing the atomic site-dependent g factor within a single magnetic molecule
      via the extended Kondo effect.
AB  - The site-dependent g factor of a single magnetic molecule, with intramolecular
      resolution, is demonstrated for the first time by low-temperature, high-magnetic
      field scanning tunneling microscopy of dehydrogenated Mn-phthalocyanine molecules
      on Au(111). This is achieved by exploring the magnetic-field dependence of the
      extended Kondo effect at different atomic sites of the molecule. Importantly, an
      inhomogeneous distribution of the g factor inside a single molecule is revealed.
      Our results open up a new route to access local spin properties within a single
      molecule. 

PMID- 25860764
TI  - Fluctuation-dissipation relations of a tunnel junction driven by a quantum
      circuit.
AB  - We derive fluctuation-dissipation relations for a tunnel junction driven through
      a resonator displaying strong quantum fluctuations. We find that the fluctuation
      dissipation relations derived for classical external drives hold, provided the
      effect of the circuit's quantum fluctuations is incorporated into the modified
      nonlinear current voltage characteristics. We also demonstrate that all
      quantities measured under a time dependent bias can be reconstructed from their
      values measured under a dc bias using photoassisted tunneling relations. We
      confirm these predictions by implementing the circuit and measuring the dc
      current through the junction, its high frequency admittance, and its current
      noise at the frequency of the resonator. 

PMID- 25860765
TI  - Persistence of a two-dimensional topological insulator state in wide HgTe quantum
      wells.
AB  - Our experimental studies of electron transport in wide (14 nm) HgTe quantum wells
      confirm the persistence of a two-dimensional topological insulator state reported
      previously for narrower wells, where it was justified theoretically. Comparison
      of local and nonlocal resistance measurements indicate edge state transport in
      the samples of about 1 mm size at temperatures below 1 K. Temperature dependence
      of the resistances suggests an insulating gap of the order of a few meV. In
      samples with sizes smaller than 10  MUm a quasiballistic transport via the edge
      states is observed. 

PMID- 25860766
TI  - Theory of light emission from quantum noise in plasmonic contacts: above
      threshold emission from higher-order electron-plasmon scattering.
AB  - We develop a theoretical framework for the description of light emission from
      plasmonic contacts based on the nonequilibrium Green function formalism. Our
      theory establishes a fundamental link between the finite-frequency quantum noise
      and ac conductance of the contact and the light emission. Calculating the quantum
      noise to higher orders in the electron-plasmon interaction, we identify a plasmon
      induced electron-electron interaction as the source of experimentally observed
      above-threshold light emission from biased STM contacts. Our findings provide
      important insight into the effect of interactions on the light emission from
      atomic-scale contacts. 

PMID- 25860767
TI  - Landau level spectroscopy of electron-electron interactions in graphene.
AB  - We present magneto-Raman scattering studies of electronic inter-Landau level
      excitations in quasineutral graphene samples with different strengths of Coulomb
      interaction. The band velocity associated with these excitations is found to
      depend on the dielectric environment, on the index of Landau level involved, and
      to vary as a function of the magnetic field. This contradicts the single-particle
      picture of noninteracting massless Dirac electrons but is accounted for by theory
      when the effect of electron-electron interaction is taken into account. Raman
      active, zero-momentum inter-Landau level excitations in graphene are sensitive to
      electron-electron interactions due to the nonapplicability of the Kohn theorem in
      this system, with a clearly nonparabolic dispersion relation. 

PMID- 25860768
TI  - Detection of a spin-triplet superconducting phase in oriented polycrystalline
      U(2)PtC(2) samples using ^(195)Pt nuclear magnetic resonance.
AB  - Nuclear magnetic resonance (NMR) measurements on the ^{195}Pt nucleus in an
      aligned powder of the moderately heavy-fermion material U_{2}PtC_{2} are
      consistent with spin-triplet pairing in its superconducting state. Across the
      superconducting transition temperature and to much lower temperatures, the NMR
      Knight shift is temperature independent for field both parallel and perpendicular
      to the tetragonal c axis, expected for triplet equal-spin pairing
      superconductivity. The NMR spin-lattice relaxation rate 1/T_{1}, in the normal
      state, exhibits characteristics of ferromagnetic fluctuations, compatible with an
      enhanced Wilson ratio. In the superconducting state, 1/T_{1} follows a power law
      with temperature without a coherence peak giving additional support that
      U_{2}PtC_{2} is an unconventional superconductor. Bulk measurements of the ac
      susceptibility and resistivity indicate that the upper critical field exceeds the
      Pauli limiting field for spin-singlet pairing and is near the orbital limiting
      field, an additional indication for spin-triplet pairing. 

PMID- 25860769
TI  - Infinitely dimensional lax structure for the one-dimensional Hubbard model.
AB  - We report a two-parametric irreducible infinitely dimensional representation of
      the Lax integrability condition for the Fermi Hubbard chain. In addition to being
      of fundamental interest, hinting at possible novel quantum symmetry of the model,
      our construction allows for an explicit representation of an exact steady state
      many-body density operator for a nonequilibrium boundary-driven Hubbard chain
      with arbitrary (asymmetric) particle source (sink) rates at the left (right) end
      of the chain and with arbitrary boundary values of chemical potentials. 

PMID- 25860770
TI  - Guiding electromagnetic waves around sharp corners: topologically protected
      photonic transport in metawaveguides.
AB  - The wave nature of radiation prevents its reflections-free propagation around
      sharp corners. We demonstrate that a simple photonic structure based on a
      periodic array of metallic cylinders attached to one of the two confining metal
      plates can emulate spin-orbit interaction through bianisotropy. Such a
      metawaveguide behaves as a photonic topological insulator with complete
      topological band gap. An interface between two such structures with opposite
      signs of the bianisotropy supports topologically protected surface waves, which
      can be guided without reflections along sharp bends of the interface. 

PMID- 25860771
TI  - Instability of a Mobius strip minimal surface and a link with systolic geometry.
AB  - We describe the first analytically tractable example of an instability of a
      nonorientable minimal surface under parametric variation of its boundary. A one
      parameter family of incomplete Meeks Mobius surfaces is defined and shown to
      exhibit an instability threshold as the bounding curve is opened up from a double
      covering of the circle. Numerical and analytical methods are used to determine
      the instability threshold by solution of the Jacobi equation on the double
      covering of the surface. The unstable eigenmode shows excellent qualitative
      agreement with that found experimentally for a closely related surface. A
      connection is proposed between systolic geometry and the instability by showing
      that the shortest noncontractable closed geodesic on the surface (the systolic
      curve) passes near the maximum of the unstable eigenmode. 

PMID- 25860772
TI  - Orientational alignment of amyloidogenic proteins in pre-aggregated solutions.
AB  - In the present study we combine dielectric relaxation spectroscopy with
      generalized Born simulations to explore the role of orientational order for
      protein aggregation in solutions of bovine pancreatic insulin at various pH
      conditions. Under aggregation-prone conditions at low pH, insulin monomers prefer
      antiparallel dipole alignments, which are consistent with the orientation of the
      monomeric subunits in the dimer structure. This alignment is also true for two
      dimers, suggesting that already at moderate protein concentrations the species
      assemble in equilibrium clusters, in which the molecules adopt preferred
      orientations also found for the protomers of the corresponding oligomers. 

PMID- 25860773
TI  - Microscale patches of nonmotile phytoplankton.
AB  - Phytoplankton cells have evolved sophisticated strategies for actively responding
      to environmental signals, most notably to mechanical stresses of hydrodynamic
      origin. A largely unanswered question, however, is the significance of these
      cellular responses for the largely heterogeneous spatial distribution of cells
      found in the oceans. Motivated by the physiological regulation of buoyancy
      prevalent in nonmotile phytoplankton species, we solve here a minimal model for
      "active" sinking that incorporates these cellular responses. Within this model,
      we show how buoyancy regulation leads to intense patchiness for nonmotile species
      as compared to passive tracers, resulting in important variations in settling
      speeds and, as a consequence, determining escape rates to the deep ocean. 

PMID- 25860774
TI  - Temperature dependence of charge carrier generation in organic photovoltaics.
AB  - The charge generation mechanism in organic photovoltaics is a fundamental yet
      heavily debated issue. All the generated charges recombine at the open-circuit
      voltage (V_{OC}), so that investigation of recombined charges at V_{OC} provides
      a unique approach to understanding charge generation. At low temperatures, we
      observe a decrease of V_{OC}, which is attributed to reduced charge separation.
      Comparison between benchmark polymer:fullerene and polymer:polymer blends
      highlights the critical role of charge delocalization in charge separation and
      emphasizes the importance of entropy in charge generation. 

PMID- 25860775
TI  - Patient experience and satisfaction with inpatient service: development of short
      form survey instrument measuring the core aspect of inpatient experience.
AB  - Patient experience reflects quality of care from the patients' perspective;
      therefore, patients' experiences are important data in the evaluation of the
      quality of health services. The development of an abbreviated, reliable and valid
      instrument for measuring inpatients' experience would reflect the key aspect of
      inpatient care from patients' perspective as well as facilitate quality
      improvement by cultivating patient engagement and allow the trends in patient
      satisfaction and experience to be measured regularly. The study developed a short
      form inpatient instrument and tested its ability to capture a core set of
      inpatients' experiences. The Hong Kong Inpatient Experience Questionnaire (HKIEQ)
      was established in 2010; it is an adaptation of the General Inpatient
      Questionnaire of the Care Quality Commission created by the Picker Institute in
      United Kingdom. This study used a consensus conference and a cross-sectional
      validation survey to create and validate a short-form of the Hong Kong Inpatient
      Experience Questionnaire (SF-HKIEQ). The short-form, the SF-HKIEQ, consisted of
      18 items derived from the HKIEQ. The 18 items mainly covered relational aspects
      of care under four dimensions of the patient's journey: hospital staff, patient
      care and treatment, information on leaving the hospital, and overall impression.
      The SF-HKIEQ had a high degree of face validity, construct validity and internal
      reliability. The validated SF-HKIEQ reflects the relevant core aspects of
      inpatients' experience in a hospital setting. It provides a quick reference tool
      for quality improvement purposes and a platform that allows both healthcare staff
      and patients to monitor the quality of hospital care over time. 

PMID- 25860776
TI  - Effect of Different Omega-6/Omega-3 Polyunsaturated Fatty Acid Ratios on the
      Formation of Monohydroxylated Fatty Acids in THP-1 Derived Macrophages.
AB  - Omega-6 and omega-3 polyunsaturated fatty acids (n-6 and n-3 PUFA) can modulate
      inflammatory processes. In western diets, the content of n-6 PUFA is much higher
      than that of n-3 PUFA, which has been suggested to promote a pro-inflammatory
      phenotype. The aim of this study was to analyze the effect of modulating the n
      6/n-3 PUFA ratio on the formation of monohydroxylated fatty acid (HO-FAs) derived
      from the n-6 PUFA arachidonic acid (AA) and the n-3 PUFAs eicosapentaenoic acid
      (EPA) and docosahexaenoic acid (DHA) in THP-1 macrophages by means of LC-MS.
      Lipid metabolites were measured in THP-1 macrophage cell pellets. The
      concentration of AA-derived hydroxyeicosatetraenoic acids (HETEs) was not
      significantly changed when incubated THP-1 macrophages in a high AA/(EPA+DHA)
      ratio of 19/1 vs. a low ratio AA/(EPA+DHA) of 1/1 (950.6 +/- 110 ng/mg vs. 648.2
      +/- 92.4 ng/mg, p = 0.103). Correspondingly, the concentration of EPA-derived
      hydroxyeicosapentaenoic acids (HEPEs) and DHA-derived hydroxydocosahexaenoic
      acids (HDHAs) were significantly increased (63.9 +/- 7.8 ng/mg vs. 434.4 +/- 84.3
      ng/mg, p = 0.012 and 84.9 +/- 18.3 ng/mg vs. 439.4 +/- 82.7 ng/mg, p = 0.014,
      respectively). Most notable was the strong increase of 18-hydroxyeicosapentaenoic
      acid (18-HEPE) formation in THP-1 macrophages, with levels of 170.9 +/- 40.2
      ng/mg protein in the high n-3 PUFA treated cells. Thus our data indicate that THP
      1 macrophages prominently utilize EPA and DHA for monohydroxylated metabolite
      formation, in particular 18-HEPE, which has been shown to be released by
      macrophages to prevent pressure overload-induced maladaptive cardiac remodeling. 

PMID- 25860777
TI  - A structure-based classification and analysis of protein domain family binding
      sites and their interactions.
AB  - While the number of solved 3D protein structures continues to grow rapidly, the
      structural rules that distinguish protein-protein interactions between different
      structural families are still not clear. Here, we classify and analyse the
      secondary structural features and promiscuity of a comprehensive non-redundant
      set of domain family binding sites (DFBSs) and hetero domain-domain interactions
      (DDIs) extracted from our updated KBDOCK resource. We have partitioned 4001 DFBSs
      into five classes using their propensities for three types of secondary
      structural elements ("alpha" for helices, "beta" for strands, and "gamma" for
      irregular structure) and we have analysed how frequently these classes occur in
      DDIs. Our results show that beta elements are not highly represented in DFBSs
      compared to alpha and gamma elements. At the DDI level, all classes of binding
      sites tend to preferentially bind to the same class of binding sites and
      alpha/beta contacts are significantly disfavored. Very few DFBSs are promiscuous:
      80% of them interact with just one Pfam domain. About 50% of our Pfam domains
      bear only one single-partner DFBS and are therefore monogamous in their
      interactions with other domains. Conversely, promiscuous Pfam domains bear
      several DFBSs among which one or two are promiscuous, thereby multiplying the
      promiscuity of the concerned protein. 

PMID- 25860778
TI  - What we know and what we do not know about factors associated with and
      interventions to promote antiretroviral adherence.
AB  - Antiretroviral therapy (ART) adherence remains critical for achieving successful
      outcomes. Factors affecting ART adherence can occur at the individual level or be
      related to the treatment regimen, daily schedule, and/or interpersonal
      relationships. While treatment-related barriers have diminished with recent
      simplified ART regimens, guidelines still recommend considering regimen
      simplicity. ART readiness should be assessed prior to starting ART, with follow
      up adherence assessments once ART is initiated, and at all subsequent clinical
      visits. Adherence interventions work best when multifaceted, targeted for at-risk
      and nonadherent participants, and tailored to individuals' needs. Successful
      interventions have included education and counseling, provision of social
      support, directly observed therapy, and financial incentives. Pillboxes and two
      way short-text messaging service (SMS) reminders have been shown to be effective
      and are widely recommended tools for promoting ART adherence. Further research is
      needed to determine the optimal combination of adherence interventions, as well
      as generalizability, implementation, and cost-effectiveness. 

PMID- 25860779
TI  - Neuroimaging findings in disruptive behavior disorders.
AB  - Decades of research have shown that youths with disruptive behavior disorders
      (DBD) are a heterogeneous population. Over the past 20 years, researchers have
      distinguished youths with DBD as those displaying high (DBD/HCU) versus low
      (DBD/LCU) callous-unemotional (CU) traits. These traits include flat affect and
      reduced empathy and remorse, and are associated with more severe, varied, and
      persistent patterns of antisocial behavior and aggression. Conduct problems in
      youths with HCU and LCU are thought to reflect distinct causal vulnerabilities,
      with antisocial behavior in youths with DBD/HCU reflecting a predominantly
      genetic etiology, while antisocial behavior in youths with DBD/LCU is associated
      primarily with environmental influences. Here we selectively review recent
      functional (fMRI) and structural (sMRI) magnetic resonance imaging research on
      DBD, focusing particularly on the role of CU traits. First, fMRI studies
      examining the neural correlates of affective stimuli, emotional face processing,
      empathy, theory of mind, morality, and decision-making in DBD are discussed. This
      is followed by a review of the studies investigating brain structure and
      structural connectivity in DBD. Next, we highlight the need to further
      investigate females and the role of sex differences in this population. We
      conclude the review by identifying potential clinical implications of this
      research. 

PMID- 25860780
TI  - Marjolin's Ulcers: A Case Series and Literature Review.
AB  - BACKGROUND: A Marjolin's ulcer describes malignant degeneration in any chronic
      wound. The majority of cases arise in burn scars and are often latent for
      decades. MATERIALS AND METHODS: This case series presents 6 patients with an
      average age of 63 years with Marjolin's ulcers (both acute and chronic). A review
      of the literature was also undertaken. These cases underscore the aggressive
      course and poor prognosis associated with Marjolin's ulcers and the importance of
      recognizing the potential for malignant transformation of a chronic wound.
      RESULTS: In the reported cases, the ulcers were found on the upper and lower
      extremity, flank, and over the sacrum, emphasizing the propensity of these ulcers
      to arise in nearly any location. Squamous cell carcinoma is the most prevalent
      malignancy identified in Marjolin's ulcers and was confirmed in all patients in
      this study. Patients underwent surgical resection, and all patients eventually
      succumbed to the disease. CONCLUSION: Based on observations and a review of the
      literature, early detection and aggressive management with wide local excision
      and prompt coverage yield optimal results when treating patients with Marjolin's
      ulcers.

PMID- 25860781
TI  - The effects of gravity on the fluid-handling properties of wound dressings
      covered with compression bandages: results of a pilot laboratory investigation.
AB  - INTRODUCTION: The management of exudate from leg ulcers remains a major challenge
      for health care practitioners. Many different dressings are available for this
      purpose, often used in conjunction with graduated external compression provided
      by extensible bandages applied in different configurations to achieve the
      required physiological effect. Although a significant amount of data has been
      published on the fluid-handling properties of some of these primary dressings,
      this has mainly been derived from laboratory studies using standard tests
      conducted in the horizontal plane, often without the addition of a secondary
      compression dressing. MATERIALS AND METHODS: A review of the literature failed to
      identify any publications which examined either the effects of compression
      bandages or gravity upon dressings tested in the vertical plane, simulating
      normal conditions of use. The present study was therefore undertaken to
      investigate the effect of both of these factors. RESULTS: While the application
      of multiple layers of bandages were found to have relatively little effect upon
      the loss of moisture vapor from a given dressing, compression and the effects of
      gravity were, in some instances, shown to significantly accelerate the rate of
      dressing failure, although important differences between products were noted in
      this regard. CONCLUSION: As a result of this work it is proposed that new test
      methods be devised which take account of both parameters to better inform
      potential users of the relative merits of various available dressing materials.  
      .

PMID- 25860782
TI  - Postoperative carbon ion radiotherapy for keloids: a preliminary report of 16
      cases and review of the literature.
AB  - OBJECTIVES: Radiotherapy for the management of keloids was first introduced in
      1906, yet 107 years later optimal protocol has not yet been established. Most
      studies have been conducted using x-ray, beta-ray, or gamma-ray. However, for
      high linear energy transfer radiation, clinical data are scarce. The aim of this
      study was to examine the efficacy and safety of postoperative carbon ion
      radiotherapy for keloids. MATERIAL AND METHODS: Case records of 16 patients with
      20 keloids, who were given postoperative carbon ion radiotherapy with 16GyE/8
      fractions in the therapy terminal at the Heavy Ion Research Facility in Lanzhou
      at the Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, China,
      were retrospectively reviewed. RESULTS: In a mean follow-up period of 29.7 months
      (range 24.3-35.3 months), overall survival and 95% success rates were achieved.
      No grade 3 or higher toxicity and complication occurred, and none of the 16
      patients presented with local or systemic malignancy during the follow-up period.
      CONCLUSION: Here, the first evidence of postoperative carbon ion radiotherapy for
      keloids is provided. Surgical excision and immediate postoperative carbon ion
      radiotherapy is well tolerated and should be considered as a potential curative
      treatment modality of keloids in certain cases.

PMID- 25860783
TI  - Combined conservative and surgical management for aplasia cutis congenita: a case
      report and review of the literature.
AB  - Aplasia cutis congenita is a rare group of disorders, characterized by the
      localized or widespread absence of skin involving the epidermis, dermis, and
      subcutaneous tissue such as muscle and bone. Here, a case of extensive aplasia
      cutis congenita involving the trunk, scalp, and bilateral thighs is reported. The
      trunk defect was successfully treated by a combination of conservative and
      surgical approaches, including allograft application to decrease size followed by
      split-thickness skin autografts to close the defect. The donor site was
      completely healed on the 7th postoperative day. This case and a review of the
      literature focusing on treatment is discussed.    . 

PMID- 25860785
TI  - Addressing the human resources for health crisis through task-shifting and
      retention: results from the Africa Health Systems Initiative Support to African
      Research Partnerships program.

PMID- 25860784
TI  - Peptide Triazole Inactivators of HIV-1 Utilize a Conserved Two-Cavity Binding
      Site at the Junction of the Inner and Outer Domains of Env gp120.
AB  - We used coordinated mutagenesis, synthetic design, and flexible docking to
      investigate the structural mechanism of Env gp120 encounter by peptide triazole
      (PT) inactivators of HIV-1. Prior results demonstrated that the PT class of
      inhibitors suppresses binding at both CD4 and coreceptor sites on Env and
      triggers gp120 shedding, leading to cell-independent irreversible virus
      inactivation. Despite these enticing anti-HIV-1 phenotypes, structural
      understanding of the PT-gp120 binding mechanism has been incomplete. Here we
      found that PT engages two inhibitor ring moieties at the junction between the
      inner and outer domains of the gp120 protein. The results demonstrate how
      combined occupancy of two gp120 cavities can coordinately suppress both receptor
      and coreceptor binding and conformationally entrap the protein in a destabilized
      state. The two-cavity model has common features with small molecule gp120
      inhibitor binding sites and provides a guide for further design of peptidomimetic
      HIV-1 inactivators based on the PT pharmacophore. 

PMID- 25860786
TI  - Targeted disruption of Rab10 causes early embryonic lethality.

PMID- 25860788
TI  - Correction: essential role for endogenous siRNAs during meiosis in mouse oocytes.

PMID- 25860787
TI  - [Diagnosis of periprosthetic hip infections].
AB  - The diagnosis of periprosthetic infection requires a clear definition itself and
      structured procedure concerning anamnesis, clinical examination, laboratory
      findings, puncture and imaging diagnostics. The clinical presentation may vary
      considerable due to the time of their occurrence as early, delayed, or late
      infection. Recognition of risk factors and knowledge of differential diagnoses
      facilitate and confirm the diagnosis. The synovial fluid is assessed with regard
      to leukocyte count, protein content, and glucose. Intraoperative tissue specimen
      sampling has to be performed correctly; the histopathological and microbiological
      studies must be assessed using specific criteria. The examination and
      classification of periprosthetic membranes make discrimination of the causal
      pathological mechanism possible, especially distinction between septic and
      aseptic loosening. In this manner statements with regard to etiology and
      prosthesis durability are possible. Different causative microorganisms appear
      postoperatively at specific times. Pathogens that grow as biofilms are of great
      significance, as they may compound diagnosis and therapy. Early infections are
      often caused by virulent microorganisms (S. aureus) with acute onset. Delayed
      (low grade) infections are usually caused by less virulent microorganisms, such
      as S. epidermidis or coagulase-negative staphylococci. Many diagnostic imaging
      methods have been used in the assessment of periprosthetic infection: plain
      radiographs, arthrography, ultrasonography, computed tomography, and magnetic
      resonance imaging. Nuclear medicine with bone scintigraphy or positron-emission
      tomography enhance diagnostic capabilities. Cultures of samples obtained by
      sonication of prostheses are more sensitive than conventional periprosthetic
      tissue culture. Multiplex PCR of sonication fluid is a promising test for
      diagnosis of periprosthetic joint infection. The promising diagnostic accuracy
      for interleukin-6 and procalcitonin has yet not been affirmed. 

PMID- 25860789
TI  - Development of a novel strategy to isolate lipophilic allergens (oleosins) from
      peanuts.
AB  - BACKGROUND: Peanut allergy is one of the most severe class I food allergies with
      increasing prevalence. Especially lipophilic allergens, such as oleosins, were
      found to be associated with severe symptoms, but are usually underrepresented in
      diagnostic extracts. Therefore, this study focused on isolation, molecular
      characterization and assessment of the allergenicity of peanut oleosins. METHODS
      AND RESULTS: A comprehensive method adapted for the isolation of peanut oil
      bodies of high purity was developed comprising a stepwise removal of seed storage
      proteins from oil bodies. Further separation of the oil body constituents,
      including the allergens Ara h 10, Ara h 11, the presumed allergen oleosin 3 and
      additional oleosin variants was achieved by a single run on a preparative
      electrophoresis cell. Protein identification realized by N-terminal sequencing,
      peptide mass fingerprinting and homology search revealed the presence of
      oleosins, steroleosins and a caleosin. Immunoblot analysis with sera of peanut
      allergic individuals illustrated the IgE-binding capacity of peanut-derived
      oleosins. CONCLUSION: Our method is a novel way to isolate all known
      immunologically distinct peanut oleosins simultaneously. Moreover, we were able
      to provide evidence for the allergenicity of oleosins and thus identified peanut
      oleosins as probable candidates for component-resolved allergy diagnosis.

PMID- 25860790
TI  - Comparison of arrhythmogenicity and proinflammatory activity induced by
      intramyocardial or epicardial myoblast sheet delivery in a rat model of ischemic
      heart failure.
AB  - Although cell therapy of the failing heart by intramyocardial injections of
      myoblasts to results in regenerative benefit, it has also been associated with
      undesired and prospectively fatal arrhythmias. We hypothesized that
      intramyocardial injections of myoblasts could enhance inflammatory reactivity and
      facilitate electrical cardiac abnormalities that can be reduced by epicardial
      myoblast sheet delivery. In a rat model of ischemic heart failure, myoblast
      therapy either by intramyocardial injections or epicardial cell sheets was given
      2 weeks after occlusion of the coronary artery. Ventricular premature
      contractions (VPCs) were assessed, using an implanted three-lead
      electrocardiograph at 1, 7, and 14 days after therapy, and 16-point epicardial
      electropotential mapping (EEPM) was used to evaluate ventricular
      arrhythmogenicity under isoproterenol stress. Cardiac functioning was assessed by
      echocardiography. Both transplantation groups showed therapeutic benefit over
      sham therapy. However, VPCs were more frequent in the Injection group on day 1
      and day 14 after therapy than in animals receiving epicardial or sham therapy (p
      < 0.05 and p < 0.01, respectively). EEPM under isoproterenol stress showed
      macroreentry at the infarct border area, leading to ventricular tachycardias in
      the Injection group, but not in the myoblast sheet- or sham-treated groups (p =
      0.045). Both transplantation types modified the myocardial cytokine expression
      profile. In animals receiving epicardial myoblast therapy, selective reductions
      in the expressions of interferon gamma, interleukin (IL)-1beta and IL12 were
      observed, accompanied by reduced infiltration of inflammatory CD11b- and CD68
      positive leukocytes, compared with animals receiving myoblasts as intramyocardial
      injections. Intramyocardial myoblast delivery was associated with enhanced
      inflammatory and immunomodulatory reactivity and increased frequency of VPCs. In
      comparison to intramyocardial injection, the epicardial route may serve as the
      preferred method of skeletal myoblast transplantation to treat heart failure. 

PMID- 25860792
TI  - Boosting power conversion efficiencies of quantum-dot-sensitized solar cells
      beyond 8% by recombination control.
AB  - At present, quantum-dot-sensitized solar cells (QDSCs) still exhibit moderate
      power conversion efficiency (with record efficiency of 6-7%), limited primarily
      by charge recombination. Therefore, suppressing recombination processes is a
      mandatory requirement to boost the performance of QDSCs. Herein, we demonstrate
      the ability of a novel sequential inorganic ZnS/SiO2 double layer treatment onto
      the QD-sensitized photoanode for strongly inhibiting interfacial recombination
      processes in QDSCs while providing improved cell stability. Theoretical modeling
      and impedance spectroscopy reveal that the combined ZnS/SiO2 treatment reduces
      interfacial recombination and increases charge collection efficiency when
      compared with conventional ZnS treatment alone. In line with those results,
      subpicosecond THz spectroscopy demonstrates that while QD to TiO2 electron
      transfer rates and yields are insensitive to inorganic photoanode overcoating,
      back recombination at the oxide surface is strongly suppressed by subsequent
      inorganic treatments. By exploiting this approach, CdSe(x)Te(1-x) QDSCs exhibit a
      certified record efficiency of 8.21% (8.55% for a champion cell), an improvement
      of 20% over the previous record high efficiency of 6.8%, together with an
      additional beneficial effect of improved cell stability.

PMID- 25860793
TI  - Cytomixis in the cereal (Gramineae) microsporogenesis.
AB  - The specific features in behavior of the nuclei and chromatin migrating through
      cytomictic channels as well as in formation of micronuclei in the cereal
      microsporogenesis have been studied. Immunofluorescence microscopy has allowed
      for demonstration that the tubulin cytoskeleton does not play a significant role
      in the intercellular migration of nuclei. Potential involvement of the actin
      cytoskeleton and SUN-KASH linker complexes in cytomixis is discussed. Comparative
      analysis of the published and own data suggests that the cytological patterns of
      cytomixis in monocots and dicots are conserved. As has been shown, each higher
      ploidy level in the polyploid series of the family Gramineae is accompanied by an
      increase in the rate of cytomixis independently of individual species. The
      results confirm the assumption on a correlation between the rate of cytomixis,
      ploidy level, and genome balance.

PMID- 25860794
TI  - Normal muscle structure, growth, development, and regeneration.
AB  - Knowledge about biochemical, structural and physiological aspects, and properties
      regarding the skeletal muscle has been widely obtained in the last decades.
      Muscle disorders, mainly represented in neuromuscular clinical practice by
      acquired and hereditary myopathies, are well-recognized and frequently diagnosed
      in practice. Most clinical complaints and biochemical characterizations of each
      myopathy depends on the appropriate knowledge and interpretation of pathological
      findings and their comparison with normal muscle findings. Great improvement has
      been obtained in the last decades mainly involving the mechanisms of normal
      muscle architecture and physiological function in the healthy individuals.
      Genetic mechanisms have also been widely studied. We provide an extensive
      literature review involving current knowledge regarding muscle cell structure and
      function and embryological and regenerative processes linked to muscle lesion. An
      updated comprehensive description involving the main nuclear genomic regulatory
      mechanisms of muscle regeneration and embryogenesis is provided in this review. 

PMID- 25860796
TI  - [Editorial].

PMID- 25860795
TI  - Impaired Statistical Learning in Developmental Dyslexia.
AB  - PURPOSE: Developmental dyslexia (DD) is commonly thought to arise from
      phonological impairments. However, an emerging perspective is that a more general
      procedural learning deficit, not specific to phonological processing, may
      underlie DD. The current study examined if individuals with DD are capable of
      extracting statistical regularities across sequences of passively experienced
      speech and nonspeech sounds. Such statistical learning is believed to be domain
      general, to draw upon procedural learning systems, and to relate to language
      outcomes. METHOD: DD and control groups were familiarized with a continuous
      stream of syllables or sine-wave tones, the ordering of which was defined by high
      or low transitional probabilities across adjacent stimulus pairs. Participants
      subsequently judged two 3-stimulus test items with either high or low statistical
      coherence as being the most similar to the sounds heard during familiarization.
      RESULTS: As with control participants, the DD group was sensitive to the
      transitional probability structure of the familiarization materials as evidenced
      by above-chance performance. However, the performance of participants with DD was
      significantly poorer than controls across linguistic and nonlinguistic stimuli.
      In addition, reading-related measures were significantly correlated with
      statistical learning performance of both speech and nonspeech material.
      CONCLUSION: Results are discussed in light of procedural learning impairments
      among participants with DD.

PMID- 25860797
TI  - An individual patient data meta-analysis on characteristics, treatments and
      outcomes of glioblastoma/ gliosarcoma patients with metastases outside of the
      central nervous system.
AB  - PURPOSE: To determine the characteristics, treatments and outcomes of patients
      with glioblastoma multiforme (GBM) or gliosarcoma (GS) and metastases outside of
      the central nervous system (CNS). METHODS: PubMed and Web of Science searches for
      peer-reviewed articles pertaining to GBM/ GS patients with metastatic
      dissemination were conducted using the keywords gliosarcoma, glioblastoma, GBM,
      metastasis, metastases and metastatic. Additionally, we performed hand search
      following the references from the selected papers. Cases with metastases to the
      CNS were excluded and evaluated in a separate study. RESULTS: 109 articles
      published between 1928 and 2013 were eligible. They reported on 150 patients. We
      observed a remarkable increase in the number of cases per decade over time.
      Median overall survival from diagnosis of metastasis (OSM+) was 6.0 +/- 0.8
      months and median overall survival from initial diagnosis (OSID) 13 +/- 2.4
      months. On univariate analyses, gender, age, the histological subtype, the time
      interval between initial diagnosis and diagnosis of metastasis and pulmonary
      involvement did not influence OSM+. We did not observe any substantial treatment
      progress. A comparison of the present cohort with 84 GBM/ GS patients with
      exclusive CNS dissemination suggests that metastases outside the CNS are related
      to a slightly more favorable outcome. CONCLUSIONS: The occurrence of extra-CNS
      metastasis from GBM/ GS is associated with a dismal prognosis, however it seems
      to compare slightly favorable to CNS dissemination. Crucial treatment progress
      has not been achieved over recent decades. A central registry should be
      considered to consecutively gain more information about the ideal therapeutic
      approach.

PMID- 25860798
TI  - Listeria monocytogenes: a model pathogen to study antigen-specific memory CD8 T
      cell responses.
AB  - Memory CD8 T cells play a critical role in providing protection to immune hosts
      by orchestrating rapid elimination of pathogen-infected cells after re-infection.
      Systemic bacterial infection with Listeria monocytogenes has been a favored
      approach for researchers to characterize pathogen-specific CD8 T cell responses,
      and in-depth understanding of L. monocytogenes biology has provided invaluable
      experimental tools that have been used to increase our understanding of memory
      CD8 T cell differentiation. Here, we describe how the tools from this murine
      model system of infection have been utilized to characterize pathogen-specific
      CD8 T cells in inbred and genetically diverse outbred hosts as they undergo naive
      to-memory CD8 T cell differentiation in vivo. We also discuss how studying L.
      monocytogenes-evoked CD8 T cell responses have provided insight on the degree of
      diminished T cell immunity in clinically relevant conditions such as sepsis and
      obesity. Overall, this review will highlight how infection with the intracellular
      pathogen L. monocytogenes has enabled analysis of systemic CD8 T cell responses
      and greatly contributed to what is known about memory CD8 T cell generation and
      differentiation. 

PMID- 25860799
TI  - Update on genetics and pathogenesis of autoinflammatory diseases: the last 2
      years.
AB  - Autoinflammatory diseases are a genetically heterogeneous group of rheumatologic
      diseases that are driven by abnormal activation of the innate immune system.
      Patients present with recurrent episodes of systemic inflammation and a spectrum
      of organ-specific comorbidities. These diseases are mediated by the
      overproduction of various inflammatory cytokines, such as IL-1, IL-18, IL-6,
      TNFalpha, and type I interferon. Treatments with biologic agents that inhibit
      these cytokines have been very efficient in most patients. During the past 2
      years, remarkable progress has been made in the identification of disease
      associated genes owing mostly to new technologies. Next generation sequencing
      technologies (NGS) have become instrumental in finding single-gene defects in
      undiagnosed patients with early onset symptoms. NGS has advanced the field of
      autoinflammation by identifying disease-causing genes that point to pathways not
      known to regulate cytokine signaling or inflammation. They include a protein that
      has a role in differentiation of myeloid cells, a ubiquitously expressed enzyme
      that catalyzes the addition of the CCA terminus to the 3-prime end of tRNA
      precursors, and an enzyme that catalyzes the oxidation of a broad range of
      substrates. Lastly, newly described mutations have informed a whole new dimension
      on genotype-phenotype relationships. Mutations in the same gene can give rise to
      a range of phenotypes with a common inflammatory component. This suggests greater
      than anticipated contributions by modifying alleles and environmental factors to
      disease expressivity. 

PMID- 25860800
TI  - Effector CD8 T cell immunity in microsporidial infection: a lone defense
      mechanism.
AB  - Microsporidia is a group of pathogens, which can pose severe risks to the
      immunocompromised population such as HIV-infected individuals. The expertise to
      diagnose these pathogens is limited and therefore their prevalence is believed to
      be much higher than what is currently known. In a mouse model of infections, it
      has been reported that CD8 T cells are the primary effector cells responsible for
      protecting the infected host. As the infection is acquired via per-oral route,
      CD8 T cells in the gut compartment apparently act as a first line of defense
      against the pathogens. Thus, generation of a robust CD8 T cell response that
      exhibits polyfunctional ability is critical for host survival. In this review, we
      describe the effector CD8 T cells generated during microsporidial infection and
      underline the factors that may be essential for the elicitation of protective
      immunity against this understudied but significant pathogen. Overall, this review
      will highlight the necessity for a better understanding of the development of the
      CD8 T cell response in gut associated lymphoid tissue (GALT) and provide some
      insights into therapies that may be used to restore defective CD8 T cell
      functionality in an immunocompromised situation. 

PMID- 25860802
TI  - Strategies for achieving high sequencing accuracy for low diversity samples and
      avoiding sample bleeding using illumina platform.
AB  - Sequencing microRNA, reduced representation sequencing, Hi-C technology and any
      method requiring the use of in-house barcodes result in sequencing libraries with
      low initial sequence diversity. Sequencing such data on the Illumina platform
      typically produces low quality data due to the limitations of the Illumina
      cluster calling algorithm. Moreover, even in the case of diverse samples, these
      limitations are causing substantial inaccuracies in multiplexed sample assignment
      (sample bleeding). Such inaccuracies are unacceptable in clinical applications,
      and in some other fields (e.g. detection of rare variants). Here, we discuss how
      both problems with quality of low-diversity samples and sample bleeding are
      caused by incorrect detection of clusters on the flowcell during initial
      sequencing cycles. We propose simple software modifications (Long Template
      Protocol) that overcome this problem. We present experimental results showing
      that our Long Template Protocol remarkably increases data quality for low
      diversity samples, as compared with the standard analysis protocol; it also
      substantially reduces sample bleeding for all samples. For comprehensiveness, we
      also discuss and compare experimental results from alternative approaches to
      sequencing low diversity samples. First, we discuss how the low diversity
      problem, if caused by barcodes, can be avoided altogether at the barcode design
      stage. Second and third, we present modified guidelines, which are more stringent
      than the manufacturer's, for mixing low diversity samples with diverse samples
      and lowering cluster density, which in our experience consistently produces high
      quality data from low diversity samples. Fourth and fifth, we present rescue
      strategies that can be applied when sequencing results in low quality data and
      when there is no more biological material available. In such cases, we propose
      that the flowcell be re-hybridized and sequenced again using our Long Template
      Protocol. Alternatively, we discuss how analysis can be repeated from saved
      sequencing images using the Long Template Protocol to increase accuracy. 

PMID- 25860801
TI  - Melanocortins contribute to sequential differentiation and enucleation of human
      erythroblasts via melanocortin receptors 1, 2 and 5.
AB  - In this study, we showed that adrenocorticotropic hormone (ACTH) promoted
      erythroblast differentiation and increased the enucleation ratio of
      erythroblasts. Because ACTH was contained in hematopoietic medium as
      contamination, the ratio decreased by the addition of anti-ACTH antibody (Ab).
      Addition of neutralizing Abs (nAbs) for melanocortin receptors (MCRs) caused
      erythroblast accumulation at specific stages, i.e., the addition of anti-MC2R nAb
      led to erythroblast accumulation at the basophilic stage (baso-E), the addition
      of anti-MC1R nAb caused accumulation at the polychromatic stage (poly-E), and the
      addition of anti-MC5R nAb caused accumulation at the orthochromatic stage (ortho
      E). During erythroblast differentiation, ERK, STAT5, and AKT were consecutively
      phosphorylated by erythropoietin (EPO). ERK, STAT5, and AKT phosphorylation was
      inhibited by blocking MC2R, MC1R, and MC5R, respectively. Finally, the
      phosphorylation of myosin light chain 2, which is essential for the formation of
      contractile actomyosin rings, was inhibited by anti-MC5R nAb. Taken together, our
      study suggests that MC2R and MC1R signals are consecutively required for the
      regulation of EPO signal transduction in erythroblast differentiation, and that
      MC5R signal transduction is required to induce enucleation. Thus, melanocortin
      induces proliferation and differentiation at baso-E, and polarization and
      formation of an actomyosin contractile ring at ortho-E are required for
      enucleation. 

PMID- 25860803
TI  - Progress on gene therapy, cell therapy, and pharmacological strategies toward the
      treatment of oculopharyngeal muscular dystrophy.
AB  - Oculopharyngeal muscular dystrophy (OPMD) is a muscle-specific, late-onset
      degenerative disorder whereby muscles of the eyes (causing ptosis), throat
      (leading to dysphagia), and limbs (causing proximal limb weakness) are mostly
      affected. The disease is characterized by a mutation in the poly(A)-binding
      protein nuclear-1 (PABPN1) gene, resulting in a short GCG expansion in the
      polyalanine tract of PABPN1 protein. Accumulation of filamentous intranuclear
      inclusions in affected skeletal muscle cells constitutes the pathological
      hallmark of OPMD. This review highlights the current translational research
      advances in the treatment of OPMD. In vitro and in vivo disease models are
      described. Conventional and experimental therapeutic approaches are discussed
      with emphasis on novel molecular therapies including the use of intrabodies, gene
      therapy, and myoblast transfer therapy. 

PMID- 25860804
TI  - Electronic transport in two-dimensional high dielectric constant nanosystems.
AB  - There has been remarkable recent progress in engineering high-dielectric constant
      two dimensional (2D) materials, which are being actively pursued for applications
      in nanoelectronics in capacitor and memory devices, energy storage, and high
      frequency modulation in communication devices. Yet many of the unique properties
      of these systems are poorly understood and remain unexplored. Here we report a
      numerical study of hopping conductivity of the lateral network of capacitors,
      which models two-dimensional insulators, and demonstrate that 2D long-range
      Coulomb interactions lead to peculiar size effects. We find that the
      characteristic energy governing electronic transport scales logarithmically with
      either system size or electrostatic screening length depending on which one is
      shorter. Our results are relevant well beyond their immediate context,
      explaining, for example, recent experimental observations of logarithmic size
      dependence of electric conductivity of thin superconducting films in the critical
      vicinity of superconductor-insulator transition where a giant dielectric constant
      develops. Our findings mark a radical departure from the orthodox view of
      conductivity in 2D systems as a local characteristic of materials and establish
      its macroscopic global character as a generic property of high-dielectric
      constant 2D nanomaterials. 

PMID- 25860805
TI  - Correction: Characterization of Tunga penetrans antigens in selected epidemic
      areas in Murang'a County in Kenya.

PMID- 25860806
TI  - Oculomotor neurocircuitry, a structural connectivity study of infantile nystagmus
      syndrome.
AB  - Infantile nystagmus syndrome (INS) is one of the leading causes of significant
      vision loss in children and affects about 1 in 1000 to 6000 births. In the
      present study, we are the first to investigate the structural pathways of
      patients and controls using diffusion tensor imaging (DTI). Specifically, three
      female INS patients from the same family were scanned, two sisters and a mother.
      Six regions of interest (ROIs) were created manually to analyze the number of
      tracks. Additionally, three ROI masks were analyzed using TBSS (Tract-Based
      Spatial Statistics). The number of fiber tracks was reduced in INS subjects,
      compared to normal subjects, by 15.9%, 13.9%, 9.2%, 18.6%, 5.3%, and 2.5% for the
      pons, cerebellum (right and left), brainstem, cerebrum, and thalamus.
      Furthermore, TBSS results indicated that the fractional anisotropy (FA) values
      for the patients were lower in the superior ventral aspects of the pons of the
      brainstem than in those of the controls. We have identified some brain regions
      that may be actively involved in INS. These novel findings would be beneficial to
      the neuroimaging clinical and research community as they will give them new
      direction in further pursuing neurological studies related to oculomotor function
      and provide a rational approach to studying INS.

PMID- 25860807
TI  - The dynamic of the splicing of bZIP60 and the proteins encoded by the spliced and
      unspliced mRNAs reveals some unique features during the activation of UPR in
      Arabidopsis thaliana.
AB  - The unfolded protein response (UPR) is a signaling pathway that is activated when
      the workload of the endoplasmic reticulum (ER) is surpassed. IRE1 is a sensor
      involved in triggering the UPR and plays a key role in the unconventional
      splicing of an mRNA leading to the formation of a transcription factor that up
      regulates the transcription of genes that play a role in restoring the
      homeostasis in the ER. In plants, bZIP60 is the substrate for IRE1; however,
      questions such as what is the dynamics of the splicing of bZIP60 and the fate of
      the proteins encoded by the spliced and unspliced forms of the mRNA, remain
      unanswered. In the present work, we analyzed the processing of bZIP60 by
      determining the levels of the spliced form mRNA in plants exposed to different
      conditions that trigger UPR. The results show that induction of ER stress
      increases the content of the spliced form of bZIP60 (bZIP60s) reaching a maximum,
      that depending on the stimuli, varied between 30 min or 2 hrs. In most cases,
      this was followed by a decrease in the content. In contrast to other eukaryotes,
      the splicing never occurred to full extent. The content of bZIP60s changed among
      different organs upon induction of the UPR suggesting that splicing is regulated
      differentially throughout the plant. In addition, we analyzed the distribution of
      a GFP-tagged version of bZIP60 when UPR was activated. A good correlation between
      splicing of bZIP60 and localization of the protein in the nucleus was observed.
      No fluorescence was observed under basal conditions, but interestingly, the
      fluorescence was recovered and found to co-localize with an ER marker upon
      treatment with an inhibitor of the proteasome. Our results indicate that the
      dynamics of bZIP60, both the mRNA and the protein, are highly dynamic processes
      which are tissue-specific and stimulus-dependent. 

PMID- 25860808
TI  - Effective population size, extended linkage disequilibrium and signatures of
      selection in the rare dog breed lundehund.
AB  - The Lundehund is an old dog breed with remarkable anatomical features including
      polydactyly in all four limbs and extraordinary flexibility of the spine. We
      genotyped 28 Lundehund using the canine Illumina high density beadchip to
      estimate the effective population size (Ne) and inbreeding coefficients as well
      as to identify potential regions of positive selection. The decay of linkage
      disequilibrium was slow with r2 = 0.95 in 50 kb distance. The last 7-200
      generations ago, Ne was at 10-13. An increase of Ne was noted in the very recent
      generations with a peak value of 19 for Ne at generation 4. The FROH estimated
      for 50-, 65- and 358-SNP windows were 0.87, 087 and 0.81, respectively. The most
      likely estimates for FROH after removing identical-by-state segments due to
      linkage disequilibria were at 0.80-0.81. The extreme loss of heterozygosity has
      been accumulated through continued inbreeding over 200 generations within a
      probably closed population with a small effective population size. The mean
      inbreeding coefficient based on pedigree data for the last 11 generations (FPed =
      0.10) was strongly biased downwards due to the unknown coancestry of the founders
      in this pedigree data. The long-range haplotype test identified regions with
      genes involved in processes of immunity, olfaction, woundhealing and neuronal
      development as potential targets of selection. The genes QSOX2, BMPR1B and PRRX2
      as well as MYOM1 are candidates for selection on the Lundehund characteristics
      small body size, increased number of digits per paw and extraordinary mobility,
      respectively. 

PMID- 25860810
TI  - Life Satisfaction Moderates the Effectiveness of a Play-Based Parenting
      Intervention in Low-Income Mothers and Toddlers.
AB  - This multi-method multi-trait study examined moderators and mediators of change
      in the context of a parenting intervention. Low-income, diverse mothers of
      toddlers (average age 30 months; N = 186, 90 girls) participated in a play-based
      intervention (Child-Oriented Play versus Play-as-Usual) aimed at increasing
      children's committed compliance and reducing opposition toward their mothers,
      observed in prohibition contexts, and at reducing mother-rated children's
      behavior problems 6 months after the intervention. Mothers' subjective sense of
      life satisfaction and fulfillment during the intervention and objective ratings
      of psychosocial functioning by clinicians, obtained in a clinical interview were
      posed as moderators, and mothers' observed power-assertive discipline immediately
      following the intervention was modeled as a mediator of its impact. We tested
      moderated mediation using structural equation modeling, with all baseline scores
      (prior to randomization) controlled. Mothers' subjective sense of life
      satisfaction moderated the impact of the intervention, but clinicians' ratings
      did not. For mothers highly satisfied with their lives, participating in Child
      Oriented Play group, compared to Play-as-Usual group, led to a reduction in power
      assertive discipline which, in turn, led to children's increased compliance and
      decreased opposition and externalizing problems. There were no effects for
      mothers who reported low life satisfaction. The study elucidates the causal
      sequence set in motion by the intervention, demonstrates the moderating role of
      mothers' subjective life satisfaction, highlights limitations of clinicians'
      ratings, and informs future prevention and intervention efforts to promote
      adaptive parenting. 

PMID- 25860809
TI  - Calcitonin gene-related peptide (CGRP) receptors are important to maintain
      cerebrovascular reactivity in chronic hypertension.
AB  - Cerebral blood flow autoregulation (CA) shifts to higher blood pressures in
      chronic hypertensive patients, which increases their risk for brain damage.
      Although cerebral vascular smooth muscle cells express the potent vasodilatatory
      peptides calcitonin gene-related peptide (CGRP) and adrenomedullin (AM) and their
      receptors (calcitonin receptor-like receptor (Calclr), receptor-modifying
      proteins (RAMP) 1 and 2), their contribution to CA during chronic hypertension is
      poorly understood. Here we report that chronic (10 weeks) hypertensive (one
      kidney-one-clip-method) mice overexpressing the Calclr in smooth muscle cells
      (CLR-tg), which increases the natural sensitivity of the brain vasculature to
      CGRP and AM show significantly better blood pressure drop-induced cerebrovascular
      reactivity than wt controls. Compared to sham mice, this was paralleled by
      increased cerebral CGRP-binding sites (receptor autoradiography), significantly
      in CLR-tg but not wt mice. AM-binding sites remained unchanged. Whereas
      hypertension did not alter RAMP-1 expression (droplet digital (dd) PCR) in either
      mouse line, RAMP-2 expression dropped significantly in both mouse lines by about
      65%. Moreover, in wt only Calclr expression was reduced by about 70% parallel to
      an increase of smooth muscle actin (Acta2) expression. Thus, chronic hypertension
      induces a stoichiometric shift between CGRP and AM receptors in favor of the CGRP
      receptor. However, the parallel reduction of Calclr expression observed in wt
      mice but not CLR-tg mice appears to be a key mechanism in chronic hypertension
      impairing cerebrovascular reactivity. 

PMID- 25860811
TI  - Perceived Expressed Emotion in Adolescents with Binge-Eating Disorder.
AB  - A sizeable body of research has documented Expressed Emotion (EE) to predict
      clinical outcomes in various psychiatric disorders, including eating disorders.
      Patients' perceptions of relative's EE, however, were found to play an important
      role in the processing of EE. This study aimed to examine the level of perceived
      EE in adolescent binge-eating disorder (BED) and its impact on eating disorder
      psychopathology. Adolescents (12-20 years) seeking treatment for BED (n = 40)
      were compared to adolescents without current or lifetime eating disorder (CG; n =
      40). Both groups were stratified according to age, sex, body mass index (BMI,
      kg/m(2)), and socio-economic status. The Five Minute Speech Sample (FMSS) and the
      Brief Dyadic Scale of EE were administered to assess patients' perceived maternal
      EE. Additionally, adolescents and mothers completed questionnaires on eating
      disorder and general psychopathology. On the FMSS, 37.5 % of patients with BED
      perceived their mothers as high EE (vs. 12.5 % in the CG). On the Brief Dyadic
      Scale of EE, patients with BED reported significantly higher levels of perceived
      maternal criticism, emotional overinvolvement, and lower levels of perceived
      warmth than controls. After controlling for the diagnosis of BED, perceived
      criticism and warmth, as assessed by questionnaire, significantly explained
      adolescents' global eating disorder psychopathology. Negative perceptions of
      maternal behavior and emotional atmosphere towards the child are characteristic
      of adolescent BED. As documented for other eating disorders, family factors are
      likely to have substantial implications for the maintenance and treatment of
      adolescent BED. 

PMID- 25860813
TI  - Correction: Pharmacokinetic characteristics, pharmacodynamic effect and in vivo
      antiviral efficacy of liver-targeted interferon alpha.

PMID- 25860812
TI  - Redox-specialized bacterioplankton metacommunity in a temperate estuary.
AB  - This study explored the spatiotemporal dynamics of the bacterioplankton community
      composition in the Gulf of Finland (easternmost sub-basin of the Baltic Sea)
      based on phylogenetic analysis of 16S rDNA sequences acquired from community
      samples via pyrosequencing. Investigations of bacterioplankton in
      hydrographically complex systems provide good insight into the strategies by
      which microbes deal with spatiotemporal hydrographic gradients, as demonstrated
      by our research. Many ribotypes were closely affiliated with sequences isolated
      from environments with similar steep physiochemical gradients and/or seasonal
      changes, including seasonally anoxic estuaries. Hence, one of the main
      conclusions of this study is that marine ecosystems where oxygen and salinity
      gradients co-occur can be considered a habitat for a cosmopolitan metacommunity
      consisting of specialized groups occupying niches universal to such environments
      throughout the world. These niches revolve around functional capabilities to
      utilize different electron receptors and donors (including trace metal and single
      carbon compounds). On the other hand, temporal shifts in the bacterioplankton
      community composition at the surface layer were mainly connected to the seasonal
      succession of phytoplankton and the inflow of freshwater species. We also
      conclude that many relatively abundant populations are indigenous and well
      established in the area. 

PMID- 25860814
TI  - Who to pay for performance? The choice of organisational level for hospital
      performance incentives.
AB  - Financial incentives for quality improvement in hospital care [known as pay for
      performance (P4P)] can be directed to either the hospital level or redistributed
      to the department level. Theoretically, performance payments distributed to lower
      organisational levels are more effective in increasing performance than payments
      directed to the hospital level, but the empirical evidence for this expectation
      is scarce. This paper compares the performance of hospital departments at
      hospitals that do and do not redistribute performance payments to the department
      level. We study a Danish P4P scheme to provide patients with case managers.
      Applying difference in differences analysis, we estimate a 5 percentage points
      higher performance at hospital departments that are subject to a direct financial
      incentive. Our results suggest that payers can improve the effectiveness of P4P
      payments by distributing payments to the department level rather than the
      hospital level. 

PMID- 25860815
TI  - The Roles of MicroRNAs in Breast Cancer.
AB  - MicroRNAs (miRNAs) constitute a large family of small, approximately 20-22
      nucleotide, non-coding RNAs that regulate the expression of target genes, mainly
      at the post-transcriptional level. Accumulating lines of evidence have indicated
      that miRNAs play important roles in the maintenance of biological homeostasis and
      that aberrant expression levels of miRNAs are associated with the onset of many
      diseases, including cancer. In various cancers, miRNAs play important roles in
      tumor initiation, drug resistance and metastasis. Recent studies reported that
      miRNAs could also be secreted via small endosome-derived vesicles called
      exosomes, which are derived from multiple cell types, including dendritic cells,
      lymphocytes, and tumor cells. Exosomal miRNAs play an important role in cell-to
      cell communication and have been investigated as prognostic and diagnostic
      biomarkers. In this review, we summarize the major findings related to the
      functions of miRNAs in breast cancer, which is the most frequent cancer in women,
      and discuss the potential clinical uses of miRNAs, including their roles as
      therapeutic targets and diagnostic markers. 

PMID- 25860816
TI  - (1)H-MRS in glutaric aciduria type 1: impact of biochemical phenotype and age on
      the cerebral accumulation of neurotoxic metabolites.
AB  - BACKGROUND: In glutaric aciduria type 1 (GA1) the neurotoxic metabolites glutaric
      acid (GA) and 3-hydroxyglutaric acid (3-OH-GA) accumulate within the brain. Due
      to limited efflux across the blood-brain-barrier biochemical monitoring of
      intracerebrally accumulating toxic metabolites is as yet not possible. AIMS: To
      investigate brain metabolic patterns in glutaric aciduria type 1 using (1)H
      magnetic resonance spectroscopy ((1)H-MRS) with focus on detecting the disease
      related neurotoxic metabolites GA and 3-OH-GA. PATIENTS AND METHODS: Short echo
      time (1)H-MRS was performed in 13 treated metabolically stable patients. Twenty
      one white matter and 16 basal ganglia spectra from 12 patients (age range 7
      months - 22 years) were included. Subgroups based on age, biochemical phenotype
      and/or associated MRI changes were compared with control spectra. RESULTS: GA was
      elevated in white matter of patients. 3-OH-GA was elevated in white matter of
      older patients with associated signal changes on MRI, which was structurally
      characterized by decreased creatine and phosphocreatine (tCr) and elevated
      choline (Cho). Metabolite changes differed with biochemical phenotype and disease
      duration: Low excretors with up to 30% residual enzyme activity had only mildly,
      non-significantly elevated GA and mildly subnormal N-acetylaspartate (tNAA). High
      excretors with complete lack of enzyme activity had significantly increased GA,
      tNAA was mildly subnormal in younger and decreased in older high excretors.
      CONCLUSIONS: GA and 3-OH-GA are detectable by in vivo (1)H-MRS, which might
      finally allow biochemical follow-up monitoring of intracerebrally accumulating
      neurotoxic metabolites in GA1. A high excreting phenotype appears to be a risk
      factor for cerebral GA accumulation and progressive neuroaxonal compromise
      despite a similar clinical course in younger high and low excreting patients.
      This might have consequences for long-term outcome.

PMID- 25860817
TI  - Endurance training ameliorates complex 3 deficiency in a mouse model of Barth
      syndrome.
AB  - Barth syndrome (BTHS) is an X-linked metabolic disorder that causes
      cardiomyopathy in infancy and is linked to mutations within the Tafazzin (TAZ)
      gene. The first mouse model, a TAZ knockdown model (TAZKD), has been generated to
      further understand the bioenergetics leading to cardiomyopathy. However, the
      TAZKD model does not show early signs of cardiomyopathy, and cardiac
      pathophysiology has not been documented until 7-8 months of age. Here we sought
      to determine the impact of endurance training on the cardiac and skeletal muscle
      phenotype in young TAZKD mice. TAZKD exercise trained (TAZKD-ET) and control
      exercise trained (CON-ET) mice underwent a 35-day swimming protocol. Non-trained
      aged matched TAZKD and CON mice were used as controls. At the end of the
      protocol, cardiac MRI was used to assess cardiac parameters. Cardiac MRI showed
      that training resulted in cardiac hypertrophy within both groups and did not
      result in a decline of ejection fraction. TAZKD mice exhibited a decrease in
      respiratory complex I, III, and IV enzymatic activity in cardiac tissue compared
      to control mice; however, training led to an increase in complex III activity in
      TAZKD-ET mice resulting in similar levels to those of CON-ET mice. (31)P magnetic
      resonance spectroscopy of the gastrocnemius showed a significantly lowered pH in
      TAZKD-ET mice post electrical-stimulation compared to CON-ET mice. Endurance
      training does not accelerate cardiac dysfunction in young TAZKD mice, but results
      in beneficial physiological effects. Furthermore, our results suggest that a
      significant drop in intracellular pH levels may contribute to oxidative
      phosphorylation defects during exercise. 

PMID- 25860818
TI  - Genetic basis of alpha-aminoadipic and alpha-ketoadipic aciduria.
AB  - Alpha-aminoadipic and alpha-ketoadipic aciduria is an autosomal recessive inborn
      error of lysine, hydroxylysine, and tryptophan degradation. To date, DHTKD1
      mutations have been reported in two alpha-aminoadipic and alpha-ketoadipic
      aciduria patients. We have now sequenced DHTKD1 in nine patients diagnosed with
      alpha-aminoadipic and alpha-ketoadipic aciduria as well as one patient with
      isolated alpha-aminoadipic aciduria, and identified causal mutations in eight. We
      report nine novel mutations, including three missense mutations, two nonsense
      mutations, two splice donor mutations, one duplication, and one deletion and
      insertion. Two missense mutations, one of which was reported before, were
      observed in the majority of cases. The clinical presentation of this group of
      patients was inhomogeneous. Our results confirm that alpha-aminoadipic and alpha
      ketoadipic aciduria is caused by mutations in DHTKD1, and further establish that
      DHTKD1 encodes the E1 subunit of the alpha-ketoadipic acid dehydrogenase complex.

PMID- 25860820
TI  - Direct identification and analysis of heavy metals in solution (Hg, Cu, Pb, Zn,
      Ni) by use of in situ electrochemical X-ray fluorescence.
AB  - The development and application of a new methodology, in situ electrochemical X
      ray fluorescence (EC-XRF), is described that enables direct identification and
      quantification of heavy metals in solution. A freestanding film of boron-doped
      diamond serves as both an X-ray window and the electrode material. The electrode
      is biased at a suitable driving potential to electroplate metals from solution
      onto the electrode surface. Simultaneously, X-rays that pass through the back
      side of the electrode interrogate the time-dependent electrodeposition process by
      virtue of the XRF signals, which are unique to each metal. In this way it is
      possible to unambiguously identify which metals are in solution and relate the
      XRF signal intensity to a concentration of metal species in solution. To increase
      detection sensitivity and reduce detection times, solution is flown over the
      electrode surface by use of a wall-jet configuration. Initial studies focused on
      the in situ detection of Pb(2+), where concentration detection limits of 99 nM
      were established in this proof-of-concept study (although significantly lower
      values are anticipated with system refinement). This is more than 3 orders of
      magnitude lower than that achievable by XRF alone in a flowing solution (0.68
      mM). In situ EC-XRF measurements were also carried out on a multimetal solution
      containing Hg(2+), Pb(2+), Cu(2+), Ni(2+), Zn(2+), and Fe(3+) (all at 10 MUM
      concentration). Identification of five of these metals was possible in one simple
      measurement. In contrast, while anodic stripping voltammetry (ASV) also revealed
      five peaks, peak identification was not straightforward, requiring further
      experiments and prior knowledge of the metals in solution. Time-dependent EC-XRF
      nucleation data for the five metals, recorded simultaneously, demonstrated
      similar deposition rates. Studies are now underway to lower detection limits and
      provide a quantitative understanding of EC-XRF responses in real, multimetal
      solutions. Finally, the production of custom-designed portable in situ EC-XRF
      instrumentation will make heavy metal analysis at the source a very realistic
      possibility. 

PMID- 25860819
TI  - Old treatments for new insights and strategies: proposed management in adults and
      children with alkaptonuria.
AB  - Alkaptonuria (AKU) is caused by deficiency of the enzyme homogentisate 1,2
      dioxygenase. It results in an accumulation of homogentisate which oxidizes
      spontaneously to benzoquinone acetate, a highly oxidant compound, which
      polymerises to a melanin-like structure, in a process called ochronosis.
      Asymptomatic during childhood, this accumulation will lead from the second decade
      of life to a progressive and severe spondylo-arthopathy, associated with
      multisystem involvement: osteoporosis/fractures, stones (renal, prostatic, gall
      bladder, salivary glands), ruptures of tendons/muscle/ligaments, renal failure
      and aortic valve disease. The pathophysiological mechanisms of AKU remain poorly
      understood, but recent advances lead us to reconsider the treatment strategy in
      AKU patients. Besides the supporting therapies (pain killers, anti-inflammatory
      drugs, physiotherapy, joints replacements and others), specific therapies have
      been considered (anti-oxidant, low protein diet, nitisinone), but clinical
      studies have failed to prove efficiency on the rheumatological lesions of the
      disease. Here we propose a treatment strategy for children and adults with AKU,
      based on a review of the latest findings on AKU and lessons from other
      aminoacipathies, especially tyrosinemias. 

PMID- 25860821
TI  - Comparison of Explant and Enzyme Digestion Methods for Ex Vivo Isolation of
      Limbal Epithelial Progenitor Cells.
AB  - PURPOSE: To compare the effectiveness of two isolation systems for stemness,
      proliferation and mesenchymal contamination of ex vivo cultured limbal epithelial
      cells (LECs). METHODS: Whole explant and dispase digestion methods were used to
      isolate LECs. For whole explant isolation, one limbal explant was cultivated up
      to four consecutive times (through LEC1 to LEC4). The performance of LECs
      isolated with both systems was evaluated according to the following parameters:
      immunofluorescent staining for adenosine 5'-triphosphate-binding cassette member
      2 (ABCG2), p63, cytokeratin 3 (K3), Ki67, and vimentin, and flow cytometry
      analysis for ABCG2, Ki67 and vimentin. RESULTS: Twelve LEC cultures were
      established using whole explant isolation, and nine LEC cultures were established
      using dispase digestion isolation. In immunofluorescent staining analysis, the
      ABCG2, p63 and Ki67 expressions were higher in LECs isolated with dispase
      compared to any LECs isolated with explant. Only the differences in ABCG2 and
      Ki67 were statistically significant. Further, LEC4 isolated with explant had the
      highest percentage of cells positive for vimentin, and LEC1 had the highest
      percentage of cells positive for K3. However, no significant differences were
      detected. In flow cytometry analysis, the expressions of ABCG2 and Ki67 were
      statistically higher for LECs isolated with dispase compared to any LECs isolated
      with explant. CONCLUSION: Dispase digestion isolation technique was significantly
      superior to explant isolation techniques in terms of progenitor and proliferative
      cell contents.

PMID- 25860822
TI  - Mental practice: a simple tool to enhance team-based trauma resuscitation.
AB  - INTRODUCTION: Effective trauma resuscitation requires the coordinated efforts of
      an interdisciplinary team. Mental practice (MP) is defined as the mental
      rehearsal of activity in the absence of gross muscular movements and has been
      demonstrated to enhance acquiring technical and procedural skills. The role of MP
      to promote nontechnical, team-based skills for trauma has yet to be investigated.
      METHODS: We randomized anaesthesiology, emergency medicine, and surgery residents
      to two-member teams randomly assigned to either an MP or control group. The MP
      group engaged in 20 minutes of MP, and the control group received 20 minutes of
      Advanced Trauma Life Support (ATLS) training. All teams then participated in a
      high-fidelity simulated adult trauma resuscitation and received debriefing on
      communication, leadership, and teamwork. Two blinded raters independently scored
      video recordings of the simulated resuscitations using the Mayo High Performance
      Teamwork Scale (MHPTS), a validated team-based behavioural rating scale. The Mann
      Whitney U-test was used to assess for between-group differences. RESULTS: Seventy
      eight residents provided informed written consent and were recruited. The MP
      group outperformed the control group with significant effect on teamwork
      behaviour as assessed using the MHPTS: r=0.67, p<0.01. CONCLUSIONS: MP leads to
      improvement in team-based skills compared to traditional simulation-based trauma
      instruction. We feel that MP may be a useful and inexpensive tool for improving
      nontechnical skills instruction effectiveness for team-based trauma care.

PMID- 25860823
TI  - An introduced competitor elevates corticosterone responses of a Native Lizard
      (Varanus varius).
AB  - Glucocorticoid hormone profiles are increasingly used as physiological markers to
      infer the strength of species interactions that can influence fitness and ensuing
      population dynamics of animals. Here we investigated two aims. First, we measured
      the effect of a 90-min capture stress protocol on the plasma corticosterone
      responses of a large native Australian lizard, the lace monitor (Varanus varius).
      Second, we compared the basal and postcapture stress corticosterone responses of
      lace monitors in habitats where they were exposed to high or low densities of the
      European red fox (Vulpes vulpes), an introduced competitor. Lace monitors
      responded to the capture stress protocol by significantly increasing plasma
      levels of corticosterone above basal at 45- and 90-min-postcapture blood-sampling
      intervals. In habitats with high fox densities, lace monitors produced a
      significantly greater basal and capture-stress-induced corticosterone response
      compared to individuals in low-fox density habitat. A significant interaction
      among fox density, time postcapture, and body condition was also found to
      influence plasma corticosterone values. These results suggest competition with
      red fox, perhaps via nutritional stress and increased hypersensitivity of the
      adrenocortical axis in lizards. At present, without further research, we do not
      understand whether such responses mediate lizard fitness or whether they have
      adaptive or maladaptive consequences for lizard populations in response to red
      fox competition. Nevertheless, our results help broaden understanding of the
      physiological implications arising from species interactions and specifically how
      introduced competitors could mediate diverse impacts on native biodiversity. 

PMID- 25860824
TI  - Foam nests provide context-dependent thermal insulation to embryos of three
      leptodactylid frogs.
AB  - The choice of adequate breeding habitat and its associated thermoregulatory
      conditions are thought to be important in the evolution of amphibian reproductive
      strategies. Among leptodactylid frogs, there is a terrestrial cline in the
      oviposition sites chosen to build foam nests for eggs. Although several functions
      have been attributed to foam nests, their role in temperature regulation for
      embryos is unclear. Here we tested the hypothesis that foam nests buffer embryos
      from variation in air temperature. We examined the degree of terrestrial nest
      sites in three species, finding a terrestrial cline of sites in terms of distance
      from water. We tested whether this nest-insulation effect varied among these
      species that differ in the degree of terrestrial nest sites and whether
      translocating nests impacted embryonic mortality. Our results demonstrate a
      negative effect of translocating aquatic nests to land, inferred from the highest
      hatching success in natural nests sites. All nests attenuated environmental
      thermal variation, but more terrestrial nests buffered embryos from a greater
      range of temperatures than did aquatic ones. Altogether, our data indicate that
      foam nests insulate embryos from daily temperature fluctuations among
      leptodactylid frogs with different degrees of terrestrial nests, which may well
      have contributed to the evolution of this reproductive strategy. 

PMID- 25860825
TI  - Comparative ecophysiology of cold-tolerance-related traits: assessing range
      expansion potential for an invasive insect at high latitude.
AB  - Survival at high latitude requires the capability to cope with seasonally imposed
      stress, such as low winter temperatures or large temperature fluctuations. The
      Colorado potato beetle, Leptinotarsa decemlineata, is an invasive pest of potato
      that has rapidly spread from low latitudes to higher latitudes. During the last
      30 years, a decrease in range expansion speed is apparent in Europe. We use a
      comparative approach to assess whether this could be due to an inability of L.
      decemlineata to cope with the harsher winters encountered at high latitude, when
      compared to two native northern chrysomelid beetles with similar overwintering
      ecology. We investigated several cold-tolerance-related physiological traits at
      different time points during winter. Cold tolerance followed a latitudinal
      pattern; the northern species were more tolerant to short-term subzero
      temperatures than the invasive L. decemlineata. The other northern species, the
      knotgrass leaf beetle, Chrysolina polita, was found to tolerate internal
      freezing. Interestingly, the pattern for overwinter survival at 5 degrees C was
      the opposite and higher in L. decemlineata than the northern species and could be
      related to behavioral differences between species in overwintering location
      selection and a potential physiological trade-off between tolerance to cold shock
      and to chronic cold exposure. Furthermore, while the northern species accumulated
      large amounts of different sugars and polyols with probable cryoprotectant
      functions, none were detected in L. decemlineata at high concentrations. This
      lack of cryoprotectant accumulation could explain the difference in cold
      tolerance between the species and also suggests that a lack of physiological
      capacity to tolerate low temperatures could slow further latitudinal range
      expansion of L. decemlineata. 

PMID- 25860826
TI  - Bioenergetics of Nutrient Reserves and Metabolism in Spiny Lobster Juveniles
      Sagmariasus verreauxi: Predicting Nutritional Condition from Hemolymph
      Biochemistry.
AB  - The nutritional condition of cultured Sagmariasus verreauxi juveniles over the
      molt and during starvation was investigated by studying their metabolism,
      bioenergetics of nutrient reserves, and hemolymph biochemistry. Juveniles were
      shown to downregulate standard metabolic rate by as much as 52% within 14 d
      during starvation. Hepatopancreas (HP) lipid was prioritized as a source of
      energy, but this reserve represented only between 1% and 13% of the total
      measured energy reserve and was used quickly during starvation, especially in the
      immediate postmolt period when as much as 60% was depleted within 3 d. Abdominal
      muscle (AM) protein represented between 74% and 90% of the total measured energy
      reserve in juvenile lobsters, and as much as 40% of available AM protein energy
      was used over 28 d of starvation after the molt. Carbohydrate reserves
      represented less than 2% of the measured total energy reserve in fed intermolt
      lobsters and provided negligible energy during starvation. Eighteen hemolymph
      parameters were measured to identify a nondestructive biomarker of condition that
      would reflect accurately the state of energy reserves of the lobster. Among
      these, the hemolymph Brix index was the most accurate and practical method to
      predict HP lipid and the total energy content of both the HP and the AM in
      juvenile S. verreauxi. The Brix index was strongly correlated with hemolymph
      proteins, triglyceride, cholesterol, calcium, and phosphorus concentrations, as
      well as lipase activity; all were useful in predicting condition. Electrolytes
      such as chloride, magnesium, and potassium and metabolites such as glucose and
      lactate were poor indicators of nutritional condition. Uric acid and the
      "albumin"-to-"globulin" ratio provided complementary information to the Brix
      index, which may assist in determining nutritional condition of wild juvenile
      lobsters of unknown intermolt development. This study will greatly assist future
      ecological studies examining the nutritional condition of juvenile lobsters in
      the wild, as well as the development of husbandry protocols and feeds for
      aquaculture. 

PMID- 25860827
TI  - Adipose Triglyceride Lipase, Not Hormone-Sensitive Lipase, Is the Primary
      Lipolytic Enzyme in Fasting Elephant Seals (Mirounga angustirostris).
AB  - Little is known about the mechanisms that allow capital breeders to rapidly
      mobilize large amounts of body reserves. Northern elephant seals (Mirounga
      angustirostris) utilize fat reserves for maternal metabolism and to create high
      fat milk for the pup. Hormone-sensitive lipase (HSL) has been hypothesized to be
      an important lipolytic enzyme in fasting seals, but the activity of HSL and
      adipose triglyceride lipase (ATGL) has not been quantified in fasting adult
      seals, nor has their relationship to milk lipid content been assessed. Blubber
      and milk samples were obtained from 18 early lactation and 19 late lactation
      females, as well as blubber from five early and five late molting female seals.
      Blubber lipolytic activity was assessed with radiometric assays. HSL activity was
      negligible in seal blubber at all fasting stages. Total triglyceride lipase
      activity was stable among early and late lactation and early molt but increased
      in late molting seals. Relative abundance of ATGL protein increased across
      fasting, but neither activity nor relative protein levels were related to
      circulating nonesterified fatty acids or milk lipid content, suggesting the
      possibility of other regulatory pathways between lipolytic activity and milk
      lipid content. These results demonstrate that HSL is not the primary lipolytic
      enzyme in fasting adult female seals and that ATGL contributes more to lipolysis
      than HSL. 

PMID- 25860828
TI  - Adiponectin and Insulin in Gray Seals during Suckling and Fasting: Relationship
      with Nutritional State and Body Mass during Nursing in Mothers and Pups.
AB  - Animals that fast during breeding and/or development, such as phocids, must
      regulate energy balance carefully to maximize reproductive fitness and survival
      probability. Adiponectin, produced by adipose tissue, contributes to metabolic
      regulation by modulating sensitivity to insulin, increasing fatty acid oxidation
      by liver and muscle, and promoting adipogenesis and lipid storage in fat tissue.
      We tested the hypotheses that (1) circulating adiponectin, insulin, or relative
      adiponectin gene expression is related to nutritional state, body mass, and mass
      gain in wild gray seal pups; (2) plasma adiponectin or insulin is related to
      maternal lactation duration, body mass, percentage milk fat, or free fatty acid
      (FFA) concentration; and (3) plasma adiponectin and insulin are correlated with
      circulating FFA in females and pups. In pups, plasma adiponectin decreased during
      suckling (linear mixed-effects model [LME]: T = 4.49; P < 0.001) and the early
      postweaning fast (LME: T = 3.39; P = 0.004). In contrast, their blubber
      adiponectin gene expression was higher during the early postweaning fast than
      early in suckling (LME: T = 2.11; P = 0.046). Insulin levels were significantly
      higher in early (LME: T = 3.52; P = 0.004) and late (LME: T = 6.99; P < 0.001)
      suckling than in fasting and, given the effect of nutritional state, were also
      positively related to body mass (LME: T = 3.58; P = 0.004). Adiponectin and
      insulin levels did not change during lactation and were unrelated to milk FFA or
      percentage milk fat in adult females. Our data suggest that adiponectin, in
      conjunction with insulin, may facilitate fat storage in seals and is likely to be
      particularly important in the development of blubber reserves in pups. 

PMID- 25860829
TI  - Ontogeny of Oxygen Storage Capacity and Diving Ability in the Southern Sea Otter
      (Enhydra lutris nereis): Costs and Benefits of Large Lungs.
AB  - Small body size, large lungs, and dense pelage contribute to the unique
      challenges faced by diving sea otters (Enhydra lutris) when compared to other
      marine mammals. Here we determine the consequences of large lungs on the
      development of diving ability in southern sea otters (Enhydra lutris nereis) by
      examining the ontogeny of blood, muscle, and lung oxygen stores and calculating
      aerobic dive limits (cADL) for immature and mature age classes. Total oxygen
      storage capacity matures rapidly in sea otters, reaching adult levels by 2 mo
      postpartum. But this result is driven by exceptional lung capacity at birth,
      followed by a decrease in mass-specific lung volume with age. Blood and muscle
      oxygen stores remain well below adult values before weaning, with large pups
      exhibiting 74% and 54% of adult values, respectively. Slow muscle development
      limits the capacity of immature sea otters to dive against high positive buoyancy
      due to comparatively large lungs. Immature sea otters diving with total lung
      capacity (TLC) experience up to twice the mass-specific positive buoyancy as
      adults diving with TLC but can reduce these forces to comparable adult levels by
      using a smaller diving lung volume (DLV). The cADL of a juvenile with DLV is 3.62
      min, while the cADL of an adult with TLC is 4.82 min. We find that the magnitude
      of positive buoyancy experienced by sea otters changes markedly with age and
      strongly influences the ontogeny of diving ability in this species. 

PMID- 25860830
TI  - Effect of reproduction on the consistency of the between-line type divergence in
      laboratory mice selected on Basal metabolic rate.
AB  - Artificial selection experiments are an effective tool for testing evolutionary
      hypotheses, because they allow one to separate genetic and environmental
      variances of the phenotype. However, it is unclear whether trait divergence
      typically selected early in life persists over an animal's life and altered
      physiological states, such as reproduction. Here we analyzed the long-term
      consistency of the between-line type divergence in basal metabolic rate (BMR)
      selected at 12 wk of age in laboratory mice. We measured BMR in nonreproducing
      and reproducing females at the age of 22 wk and then at 27 wk of age. Our results
      show that within both the reproducing group and the control group, the between
      line type separation in BMR is consistently retained over time and reproductive
      status. Metabolically active internal organs (heart, liver, kidneys, and small
      intestine) also consistently differed in size between the two line types with no
      significant long-term effect of reproduction. The observed consistency of the
      between-line type divergence in BMR suggests the existence of the persistent
      effect of the selection on metabolic traits applied early in life. Moreover, BMR
      variation achieved by means of artificial selection is considerably higher than
      that found in natural/unmanipulated populations. The latter may therefore be
      characterized by insufficient variance to statistically resolve correlations
      involving BMR. 

PMID- 25860831
TI  - Estimation of Muscle Mass by Ultrasonography Differs between Observers and Life
      States of Models in Small Birds.
AB  - Ultrasonography has proven to be a valuable noninvasive method of measure of
      muscle size in birds, but validation of its use in birds as small as black-capped
      chickadees (Poecile atricapillus; 11 g) is scarce. The effect of observers and
      life state (dead or alive) of models used for calibration on measurement quality
      is also poorly documented. Using 31 dead and 22 live chickadees, linear
      regressions between ultrasound and dissection measurements of pectoral and thigh
      muscles were fitted and compared between five different observers. R(2) values
      varied greatly between observers and were generally weaker in live birds, ranging
      between 0.02 and 0.59, despite high repeatability of measurement. Using equations
      calculated from dead birds to estimate muscle mass of live birds yielded much
      higher measurement errors (9%-18%) than when using equations calculated from live
      birds (5%-8%). Our results suggest that with careful training and using only
      calibration from live birds, ultrasonography can be a useful but limited tool to
      estimate muscle size of birds as small as the black-capped chickadee. 

PMID- 25860832
TI  - Measuring oxidative stress: the confounding effect of lipid concentration in
      measures of lipid peroxidation.
AB  - Lipid peroxidation products are widely used as markers of oxidative damage in the
      organism. To properly interpret the information provided by these markers, it is
      necessary to know potential sources of bias and control confounding factors.
      Here, we investigated the relationship between two indicators of lipid
      mobilization (circulating levels of triglycerides and cholesterol) and two common
      markers of oxidative damage (plasma levels of malondialdehyde and hydroperoxides;
      the latter estimated from the d-ROMs assay kit). The following five avian species
      were studied: red-legged partridge (Alectoris rufa), zebra finch (Taeniopygia
      guttata), spotless starling (Sturnus unicolor), marsh harrier (Circus
      aeroginosus), and Montagu's harrier (Circus pygargus). In all cases, plasma
      triglyceride levels positively and significantly correlated with lipid
      peroxidation markers, explaining between 8% and 34% of their variability. Plasma
      cholesterol, in contrast, showed a significant positive relationship only among
      spotless starling nestlings and a marginally significant association in zebra
      finches. These results indicate that lipid peroxidation marker levels covary with
      circulating lipid levels. We discuss the potential causes and implications of
      this covariation and recommend that future studies that measure oxidative damage
      using lipid peroxidation markers report both raw and relative levels (i.e.,
      corrected for circulating triglycerides). Whether the observed pattern also holds
      for other tissues and in other taxa would deserve further research. 

PMID- 25860833
TI  - Melanin chemistry and the ecology of stress.
AB  - Knowledge of melanin chemistry has important implications for the study of the
      evolutionary ecology of animal pigmentation, but the actual chemical diversity of
      these widely expressed biological pigments has been largely overlooked.
      Considering all melanin forms and the different conditions of endogenous
      oxidative stress during their synthesis provides information about physiological
      costs and benefits of different pigmentation patterns and opens a new perspective
      to understanding the evolution of color phenotypes in animals. 

PMID- 25860834
TI  - pkCSM: Predicting Small-Molecule Pharmacokinetic and Toxicity Properties Using
      Graph-Based Signatures.
AB  - Drug development has a high attrition rate, with poor pharmacokinetic and safety
      properties a significant hurdle. Computational approaches may help minimize these
      risks. We have developed a novel approach (pkCSM) which uses graph-based
      signatures to develop predictive models of central ADMET properties for drug
      development. pkCSM performs as well or better than current methods. A freely
      accessible web server (http://structure.bioc.cam.ac.uk/pkcsm), which retains no
      information submitted to it, provides an integrated platform to rapidly evaluate
      pharmacokinetic and toxicity properties.

PMID- 25860835
TI  - Impact of water regimes on an experimental community of four desert arbuscular
      mycorrhizal fungal (AMF) species, as affected by the introduction of a non-native
      AMF species.
AB  - Field studies have revealed the impact of changing water regimes on the structure
      of arbuscular mycorrhizal fungal (AMF) communities, but it is not known what
      happens to the abundance of individual AMF species within the community when the
      water conditions in the rhizosphere change. The behavior of four AMF species
      isolated from the Arabian desert (Diversispora aurantia, Diversispora omaniana,
      Septoglomus africanum, and an undescribed Paraglomus species) was investigated
      when assembled in microcosms containing Sorghum bicolor as host plant, and
      treated with various water regimes. Furthermore, the impact of invasion of these
      assemblages by Rhizophagus irregularis, an AMF species widely used in commercial
      inocula, was studied. The abundance of each AMF species in sorghum roots was
      measured by determining the transcript numbers of their large ribosomal subunit
      (rLSU) by real-time PCR, using cDNA and species-specific primers. Plant biomass
      and length of AMF extraradical hyphae were also measured. The abundance of each
      AMF species within the sorghum roots was influenced by both the water regime and
      the introduction of R. irregularis. Under dry conditions, the introduction of R.
      irregularis reduced the total abundance of all native AMF species in roots and
      also led to a reduction in the amount of extraradical mycelium, as well as to a
      partial decrease in plant biomass. The results indicate that both water regime
      and the introduction of an invasive AMF species can strongly alter the structure
      of an AMF native assemblage with a consequent impact on the entire symbiotic
      mycorrhizal relationship. 

PMID- 25860836
TI  - Towards Advancing Knowledge Translation of AAC Outcomes Research for Children and
      Youth with Complex Communication Needs.
AB  - The production of new knowledge in augmentative and alternative communication
      (AAC) requires effective processes to leverage the different perspectives of
      researchers and knowledge users and improve prospects for utilization in clinical
      settings. This article describes the motivation, planning, process, and outcomes
      for a novel knowledge translation workshop designed to influence future
      directions for AAC outcomes research for children with complex communication
      needs. Invited knowledge users from 20 pediatric AAC clinics and researchers
      engaged in the collaborative development of research questions using a framework
      designed for the AAC field. The event yielded recommendations for research and
      development priorities that extend from the early development of language,
      communication, and literacy skills in very young children, to novel but unproven
      strategies that may advance outcomes in transitioning to adulthood. 

PMID- 25860837
TI  - Requirement of DLG1 for cardiovascular development and tissue elongation during
      cochlear, enteric, and skeletal development: possible role in convergent
      extension.
AB  - The Dlg1 gene encodes a member of the MAGUK protein family involved in the
      polarization of epithelial cells. Null mutant mice for the Dlg1 gene (Dlg1-/-
      mice) exhibit respiratory failure and cyanosis, and die soon after birth.
      However, the cause of this neonatal lethality has not been determined. In the
      present study, we further examined Dlg1-/- mice and found severe defects in the
      cardiovascular system, including ventricular septal defect, persistent truncus
      arteriosus, and double outlet right ventricle, which would cause the neonatal
      lethality. These cardiovascular phenotypes resemble those of mutant mice lacking
      planar cell polarity (PCP) genes and support a recent notion that DLG1 is
      involved in the PCP pathway. We assessed the degree of involvement of DLG1 in the
      development of other organs, as the cochlea, intestine, and skeleton, in which
      PCP signaling has been suggested to play a role. In the organ of Corti, tissue
      elongation was inhibited accompanied by disorganized arrangement of the hair cell
      rows, while the orientation of the stereocilia bundle was normal. In the sternum,
      cleft sternum, abnormal calcification pattern of cartilage, and disorganization
      of chondrocytes were observed. Furthermore, shortening of the intestine, sternum,
      and long bones of the limbs was observed. These phenotypes of Dlg1-/- mice
      involving cellular disorganization and insufficient tissue elongation strongly
      suggest a defect in the convergent extension movements in these mice. Thus, our
      present results provide a possibility that DLG1 is particularly required for
      convergent extension among PCP signaling-dependent processes. 

PMID- 25860838
TI  - Full establishment of arbuscular mycorrhizal symbiosis in rice occurs
      independently of enzymatic jasmonate biosynthesis.
AB  - Development of the mutualistic arbuscular mycorrhiza (AM) symbiosis between most
      land plants and fungi of the Glomeromycota is regulated by phytohormones. The
      role of jasmonate (JA) in AM colonization has been investigated in the
      dicotyledons Medicago truncatula, tomato and Nicotiana attenuata and
      contradicting results have been obtained with respect to a neutral, promotive or
      inhibitory effect of JA on AM colonization. Furthermore, it is currently unknown
      whether JA plays a role in AM colonization of monocotyledonous roots. Therefore
      we examined whether JA biosynthesis is required for AM colonization of the
      monocot rice. To this end we employed the rice mutant constitutive
      photomorphogenesis 2 (cpm2), which is deficient in JA biosynthesis. Through a
      time course experiment the amount and morphology of fungal colonization did not
      differ between wild-type and cpm2 roots. Furthermore, no significant difference
      in the expression of AM marker genes was detected between wild type and cpm2.
      However, treatment of wild-type roots with 50 MUM JA lead to a decrease of AM
      colonization and this was correlated with induction of the defense gene PR4.
      These results indicate that JA is not required for AM colonization of rice but
      high levels of JA in the roots suppress AM development likely through the
      induction of defense. 

PMID- 25860840
TI  - Correction: an operon of three transcriptional regulators controls horizontal
      gene transfer of the integrative and conjugative element ICEclc in Pseudomonas
      knackmussii B13.

PMID- 25860839
TI  - Maximizing Iodine Contrast-to-Noise Ratios in Abdominal CT Imaging through Use of
      Energy Domain Noise Reduction and Virtual Monoenergetic Dual-Energy CT.
AB  - PURPOSE: To determine the iodine contrast-to-noise ratio (CNR) for abdominal
      computed tomography (CT) when using energy domain noise reduction and virtual
      monoenergetic dual-energy (DE) CT images and to compare the CNR to that attained
      with single-energy CT at 80, 100, 120, and 140 kV. MATERIALS AND METHODS: This
      HIPAA-compliant study was approved by the institutional review board with waiver
      of informed consent. A syringe filled with diluted iodine contrast material was
      placed into 30-, 35-, and 45-cm-wide water phantoms and scanned with a dual
      source CT scanner in both DE and single-energy modes with matched scanner output.
      Virtual monoenergetic images were generated, with energies ranging from 40 to 110
      keV in 10-keV steps. A previously developed energy domain noise reduction
      algorithm was applied to reduce image noise by exploiting information
      redundancies in the energy domain. Image noise and iodine CNR were calculated. To
      show the potential clinical benefit of this technique, it was retrospectively
      applied to a clinical DE CT study of the liver in a 59-year-old male patient by
      using conventional and iterative reconstruction techniques. Image noise and CNR
      were compared for virtual monoenergetic images with and without energy domain
      noise reduction at each virtual monoenergetic energy (in kiloelectron volts) and
      phantom size by using a paired t test. CNR of virtual monoenergetic images was
      also compared with that of single-energy images acquired with 80, 100, 120, and
      140 kV. RESULTS: Noise reduction of up to 59% (28.7 of 65.7) was achieved for DE
      virtual monoenergetic images by using an energy domain noise reduction technique.
      For the commercial virtual monoenergetic images, the maximum iodine CNR was
      achieved at 70 keV and was 18.6, 16.6, and 10.8 for the 30-, 35-, and 45-cm
      phantoms. After energy domain noise reduction, maximum iodine CNR was achieved at
      40 keV and increased to 30.6, 25.4, and 16.5. These CNRs represented improvement
      of up to 64% (12.0 of 18.6) with the energy domain noise reduction technique. For
      single-energy CT at the optimal tube potential, iodine CNR was 29.1 (80 kV), 21.2
      (80 kV), and 11.5 (100 kV). For patient images, 39% (24 of 61) noise reduction
      and 67% (0.74 of 1.10) CNR improvement were observed with the energy domain noise
      reduction technique when compared with standard filtered back-projection images.
      CONCLUSION: Iodine CNR for adult abdominal CT may be maximized with energy domain
      noise reduction and virtual monoenergetic DE CT.

PMID- 25860841
TI  - Role of Minimally Invasive Surgery in Gynecologic Oncology: An Updated Survey of
      Members of the Society of Gynecologic Oncology.
AB  - OBJECTIVES: To evaluate the current patterns of use of minimally invasive
      surgical procedures, including traditional, robotic-assisted, and single-port
      laparoscopy, by Society of Gynecologic Oncology (SGO) members and to compare the
      results to those of our 2004 and 2007 surveys. METHODS: The Society of
      Gynecologic Oncology members were surveyed through an online or mailed-paper
      survey. Data were analyzed and compared with results of our prior surveys.
      RESULTS: Four hundred six (32%) of 1279 SGO members responded. Eighty-three
      percent of respondents (n = 337) performed traditional laparoscopic surgery
      (compared with 84% in 2004 and 91% in 2007). Ninety-seven percent of respondents
      performed robotic surgery (compared with 27% in 2007). When respondents were
      asked to indicate procedures that they performed with the robot but not with
      traditional laparoscopy, 75% indicated radical hysterectomy and pelvic
      lymphadenectomy for cervical cancer. Overall, 70% of respondents indicated that
      hysterectomy and staging for uterine cancer was the procedure they most commonly
      performed with a minimally invasive approach. Only 17% of respondents who
      performed minimally invasive surgery performed single-port laparoscopy, and only
      5% of respondents indicated that single-port laparoscopy has an important or very
      important role in the field. CONCLUSIONS: Since our prior surveys, we found a
      significant increase in the overall use and indications for robotic surgery.
      Radical hysterectomy or trachelectomy and pelvic lymphadenectomy for cervical
      cancer and total hysterectomy and staging for endometrial cancer were procedures
      found to be significantly more appropriate for the robotic platform in comparison
      to traditional laparoscopy. The indications for laparoscopy have expanded beyond
      endometrial cancer staging to include surgical management of early-stage cervical
      and ovarian cancers, but the use of single-port laparoscopy remains limited.

PMID- 25860843
TI  - Mesoporous N-doped carbons prepared with thermally removable nanoparticle
      templates: an efficient electrocatalyst for oxygen reduction reaction.
AB  - Thermally removable nanoparticle templates were used for the fabrication of self
      supported N-doped mesoporous carbons with a trace amount of Fe (Fe-N/C).
      Experimentally Fe-N/C was prepared by pyrolysis of poly(2-fluoroaniline) (P2FANI)
      containing a number of FeO(OH) nanorods that were prepared by a one-pot
      hydrothermal synthesis and homogeneously distributed within the polymer matrix.
      The FeO(OH) nanocrystals acted as rigid templates to prevent the collapse of
      P2FANI during the carbonization process, where a mesoporous skeleton was formed
      with a medium surface area of about 400 m(2)/g. Subsequent thermal treatments at
      elevated temperatures led to the decomposition and evaporation of the FeO(OH)
      nanocrystals and the formation of mesoporous carbons with the surface area
      markedly enhanced to 934.8 m(2)/g. Electrochemical measurements revealed that the
      resulting mesoporous carbons exhibited apparent electrocatalytic activity for
      oxygen reduction reactions (ORR), and the one prepared at 800  degrees C (Fe-N/C
      800) was the best among the series, with a more positive onset potential (+0.98 V
      vs RHE), higher diffusion-limited current, higher selectivity (number of electron
      transfer n > 3.95 at +0.75 V vs RHE), much higher stability, and stronger
      tolerance against methanol crossover than commercial Pt/C catalysts in a 0.1 M
      KOH solution. The remarkable ORR performance was attributed to the high surface
      area and sufficient exposure of electrocatalytically active sites that arose
      primarily from N-doped carbons with minor contributions from Fe-containing
      species. 

PMID- 25860842
TI  - Sialendoscopy for Patients with Radioiodine-Induced Sialadenitis and Xerostomia.
AB  - BACKGROUND: We examined outcomes in patients treated for radioactive iodine
      induced sialadenitis (RAIS) and xerostomia with sialendoscopy. METHODS: Data was
      prospectively collected for all patients undergoing sialendoscopy for RAIS from a
      single institution. Interventional details and intraoperative findings were
      recorded. Qualitative data were obtained through patient examination, telephone
      interviews, and use of a standard quality of life questionnaire, Xerostomia
      Questionnaire. Quantitative data were obtained from patients who underwent
      sialometry. RESULTS: Twenty-six patients (24 women and 2 men; median age, 43
      years; age range, 19-57 years) underwent interventional sialendoscopy after
      conservative management of symptoms proved unsuccessful. Sialadenitis was present
      in 25 patients and xerostomia in 22 patients. Mucus plugging in the duct of the
      gland was the most common finding (22 patients) followed by stenosis (18
      patients), inflammation (eight patients), and erythema (eight patients). Median
      follow-up time was 23.4+/-12.1 months. Sixteen patients (64%) reported complete
      resolution; seven (28%), partial resolution; one (4%), no change in symptoms; and
      one (4%), regression in RAIS-related symptoms. Patients subjectively noted the
      following regarding their xerostomia symptoms: seven (31.8%) had complete
      resolution; 10 (45.5%), partial resolution; four (18.2%), no change; and one
      (4.5%), regression. Statistical analysis of the available sialometry data
      revealed a statistically significant difference in saliva production at 6 months
      following sialendoscopy for unstimulated saliva production (p=0.028). CONCLUSION:
      Sialendoscopy is an effective treatment option for the management of RAIS and
      xerostomia refractory to conservative therapy and medical management. Patients in
      our cohort report durable improvement in symptoms after intervention.

PMID- 25860844
TI  - Evaluation of recruitment and retention strategies for health workers in rural
      Zambia.
AB  - BACKGROUND: In response to Zambia's critical human resources for health
      challenges, a number of strategies have been implemented to recruit and retain
      health workers in rural and remote areas. Prior to this study, the effectiveness
      of these strategies had not been investigated. The purpose of this study was to
      determine the impacts of the various health worker retention strategies on health
      workers in two rural districts of Zambia. METHODS: Using a modified outcome
      mapping approach, cross-sectional qualitative and quantitative data were
      collected from health workers and other stakeholders through focus group
      discussions and individual interview questionnaires and were supplemented by
      administrative data. Key themes emerging from qualitative data were identified
      from transcripts using thematic analysis. Quantitative data were analyzed
      descriptively as well as by regression modelling. In the latter, the degree to
      which variation in health workers' self-reported job satisfaction, likelihood of
      leaving, and frequency of considering leaving, were modelled as functions of
      participation in each of several retention strategies while controlling for age,
      gender, profession, and district. RESULTS: Nineteen health worker recruitment and
      retention strategies were identified and 45 health care workers interviewed in
      the two districts; participation in each strategy varied from 0% to 80% of study
      participants. Although a salary top-up for health workers in rural areas was
      identified as the most effective incentive, almost none of the recruitment and
      retention strategies were significant predictors of health workers' job
      satisfaction, likelihood of leaving, or frequency of considering leaving, which
      were in large part explained by individual characteristics such as age, gender,
      and profession. These quantitative findings were consistent with the qualitative
      data, which indicated that existing strategies fail to address major problems
      identified by health workers in these districts, such as poor living and working
      conditions. CONCLUSIONS: Although somewhat limited by a small sample size and the
      cross-sectional nature of the primary data available, the results nonetheless
      show that the many health worker recruitment and retention strategies implemented
      in rural Zambia appear to have little or no impact on keeping health workers in
      rural areas, and highlight key issues for future recruitment and retention
      efforts.

PMID- 25860845
TI  - Comparative study of PCA in classification of multichannel EMG signals.
AB  - Electromyographic (EMG) signals are abundantly used in the field of
      rehabilitation engineering in controlling the prosthetic device and significantly
      essential to find fast and accurate EMG pattern recognition system, to avoid
      intrusive delay. The main objective of this paper is to study the influence of
      Principal component analysis (PCA), a transformation technique, in pattern
      recognition of six hand movements using four channel surface EMG signals from ten
      healthy subjects. For this reason, time domain (TD) statistical as well as auto
      regression (AR) coefficients are extracted from the four channel EMG signals. The
      extracted statistical features as well as AR coefficients are transformed using
      PCA to 25, 50 and 75 % of corresponding original feature vector space. The
      classification accuracy of PCA transformed and non-PCA transformed TD statistical
      features as well as AR coefficients are studied with simple logistic regression
      (SLR), decision tree (DT) with J48 algorithm, logistic model tree (LMT), k
      nearest neighbor (kNN) and neural network (NN) classifiers in the identification
      of six different movements. The Kruskal-Wallis (KW) statistical test shows that
      there is a significant reduction (P < 0.05) in classification accuracy with PCA
      transformed features compared to non-PCA transformed features. SLR with non-PCA
      transformed time domain (TD) statistical features performs better in accuracy and
      computational power compared to other features considered in this study. In
      addition, the motion control of three drives for six movements of the hand is
      implemented with SLR using TD statistical features in off-line with TMSLF2407
      digital signal controller (DSC). 

PMID- 25860846
TI  - Caudatin Inhibits Human Glioma Cells Growth Through Triggering DNA Damage
      Mediated Cell Cycle Arrest.
AB  - Caudatin, one of the species of C-21 steroidal glycosides mainly isolated from
      the root of Cynanchum bungei Decne, exhibits potent anticancer activities.
      However, the mechanism remains poorly defined. In the present study, the growth
      inhibitory effect and mechanism of caudatin on human glioma cells were evaluated
      in vitro. The results revealed that caudatin time- and dose-dependently inhibited
      U251 and U87 cells growth. Flow cytometry analysis indicated that caudatin
      induced growth inhibition against U251 and U87 cells was mainly achieved by the
      induction of G0/G1 and S-phase cell cycle arrest through triggering DNA damage,
      as convinced by the up-regulation of p53, p21, and histone phosphorylation, as
      well as the down-regulation of cyclin D1. Moreover, caudatin treatment also
      triggered the activation of ERK and inactivation of AKT pathway. LY294002 (an AKT
      inhibitor) addition enhanced caudation-induced AKT inhibition, indicating that
      caudatin inhibited U251 cells growth in an AKT-dependent manner. Taken together,
      these results indicate that caudatin may act as a novel cytostatic reagent
      against human glioma cells through the induction of DNA damage-mediated cell
      cycle arrest with the involvement of modulating MAPK and AKT pathways. 

PMID- 25860847
TI  - Talc pleurodesis improves survival of patients with malignant pleural effusions:
      case-control study.
AB  - AIM: The aim of this study is to investigate whether there was a considerable
      difference in the survival of patients with malignant pleural effusion (MPE)
      depending on the pleural effusion treatment option. METHODS: One hundred and
      seven patients with proven MPE (metastatic lung and breast cancer) were included
      in the retrospective study. Fifty six patients were treated with talc pleurodesis
      and a control group of 51 patients with similar characteristics (in age, sex and
      disease) were treated with serial thoracentesis. The patients of both groups
      underwent chemotherapy and/or radiotherapy. The overall survival and the survival
      in subgroups of patients with different tumour types and different performance
      status (PS) equal 1, 2 and 3 were compared. RESULTS: The patients who underwent
      talc pleurodesis had a longer average survival interval (MS) than the patients
      without such a treatment (n = 56; MS = 21,5 and n = 51; MS = 9 weeks,
      respectively; p < 0.001). The best results were achieved in patients with PS 1 (n
      = 16; MS = 35.5 and n = 10; MS = 11 weeks in the groups with and without talc
      pleurodesis, respectively; p < 0,001) and PS 2 (n = 27; MS = 21 and n = 30; MS =
      10 weeks in the groups with and without talc pleurodesis, respectively; p <
      0.001), whereas talc pleurodesis was not effective in PS 3 patients (n = 13; MS =
      10 and n = 11; MS = 7 weeks in the groups with and without talc pleurodesis,
      respectively; p = 0.08). Patients with the breast cancer showed a longer average
      survival interval after pleurodesis than those with the lung cancer (n = 12; MS =
      37.5 and n =  4; MS = 20 weeks in the group with the breast cancer and with the
      lung cancer, respectively; p < 0.001), whereas the median survival was not
      significantly different between those patients without pleurodesis (n = 10; MS =
      10 and n = 41; MS = 9 weeks in the group with the breast cancer and lung cancer,
      respectively; p = 0.11). CONCLUSION: The patients treated with talc pleurodesis
      had a significantly longer average survival than the patients without such a
      treatment, especially in the group with the breast cancer and in groups with
      better performance status. This may indicate that talc pleurodesis, apart from
      its symptomatic effect on the cessation of pleural effusion, may have a direct
      antitumour effect as well.

PMID- 25860848
TI  - The effects of Nigella sativa oil, thymoquinone, propolis, and caffeic acid
      phenethyl ester on radiation-induced cataract.
AB  - BACKGROUND: The aim of this study was to investigate the antioxidant and
      radioprotective effects of propolis, caffeic acid phenethyl ester (CAPE), Nigella
      sativa oil (NSO), and thymoquinone (TQ) against ionizing radiation-induced
      cataracts in lens after total cranium irradiation of rats with single dose of 5
      Gy cobalt-60 gamma rays. METHODS: A total of 74 Sprague-Dawley rats were divided
      into 8 groups to test the radioprotective effectiveness of Nigella sativa oil,
      thymoquine, propolis, or caffeic acid phenethyl ester administered by either
      orogastric tube or intraperitoneal injection. Appropriate control groups were
      also studied. RESULTS: Chylack's cataract classification was used in the study.
      At the end of the tenth day, cataracts developed in 80 % of the rats in the
      radiotherapy group. After irradiation, cataract rate dropped to 20 % in NSO, 30 %
      in propolis, 40 % in CAPE, and 50 % in TQ groups and was limited to grade 1 and
      grade 2. Cataract formation was observed the least in NSO group and the most in
      TQ group. In the irradiated (IR) group, superoxide dismutase activity was lower,
      while glutathione peroxidase and xanthine oxidase activities and malondialdehyde
      level were higher compared with the other groups. Total superoxide scavenger
      activity and nonenzymatic superoxide scavenger activity were not statistically
      significant in IR group compared with the other groups. CONCLUSIONS: The findings
      obtained in the study might suggest that propolis, CAPE, NSO, and TQ could
      prevent cataractogenesis in ionizing radiation-induced cataracts in the lenses of
      rats, wherein propolis and NSO were found to be more potent.

PMID- 25860849
TI  - Imaging findings of pulmonary granulomatosis with polyangiitis (Wegener's
      granulomatosis): lesions invading the pulmonary fissure, pleura or diaphragm
      mimicking malignancy.
AB  - BACKGROUND: Granulomatosis with polyangiitis (GPA, formerly Wegener's
      granulomatosis), in which pulmonary involvement often predominates, is a
      multisystem granulomatous, necrotizing vasculitis that affects small and medium
      sized vessels. In this study we evaluated various radiological findings of
      pulmonary GPA and focused on spiculated pulmonary lesions invading the pulmonary
      fissure, pleura or diaphragm mimicking malignancy. METHODS: This retrospective
      study included 48 patients, aged 28-73 (mean, 47.3) years, who showed either
      histopathological diagnosis of GPA (n = 39) or elevated levels of the cytoplasmic
      anti-neutrophilic cytoplasmic antibody serum marker (n = 9) between January 2003
      and December 2013. All patients received a chest computed tomography (CT), and
      the types of pulmonary lesions were defined and evaluated. RESULTS: Among the 48
      patients, 33 had abnormal pulmonary findings on CT. The most commonly detected
      pulmonary lesion types were nodules and masses (n = 126) observed in 24 patients.
      Cavitation, necrosis, spiculation and invasion of the fissure, pleura or
      diaphragm were observed in 14, 9, 10 and 6 patients, respectively. Consolidation
      was found in 14 patients and thickening of bronchial wall in 8 patients.
      CONCLUSIONS: Pulmonary lesion types of GPA have a wide spectrum, potentially
      mimicking a high number of diseases including malignancy, infection and
      noninfectious inflammatory diseases. A spiculated lung lesion invading the
      fissure, pleura or diaphragm is mostly present in malignancy, but it can be also
      seen in GPA.

PMID- 25860850
TI  - The effect of upper gastrointestinal system endoscopy process on serum oxidative
      stress levels.
AB  - Some authors have investigated the effects of oxidative stress in some process
      such as undergoing laparoscopic. However, the effect of upper gastrointestinal
      system endoscopy process on oxidative stress is unclear. We evaluated the short
      term effect of upper gastrointestinal system endoscopy process on oxidative
      stress. Thirty patients who underwent endoscopy process and 20 healthy controls
      were enrolled in the prospective study. Serum total antioxidant capacity and
      total oxidant status measurements were measured before and after endoscopy
      process. The ratio percentage of total oxidant status to total antioxidant
      capacity was regarded as oxidative stress index. Before endoscopy process, serum
      total antioxidant capacity levels were higher, while serum total oxidant status
      levels and oxidative stress index values were lower in patients than controls,
      but this difference was not statistically significant (all, p > 0.05). After
      endoscopy process, serum total antioxidant capacity and total oxidant status
      levels were significantly higher in patients than before endoscopy process (both,
      p < 0.05). However, oxidative stress index values were slight higher in patients
      but this difference was not statistically significant (p > 0.05). We observed
      that serum TAC and TOS levels were increased in patients who underwent endoscopy
      process after endoscopy process. However, short-time upper gastrointestinal
      system endoscopy process did not cause an important change in the oxidative
      stress index. Further studies enrolling a larger number of patients are required
      to clarify the results obtained here.

PMID- 25860851
TI  - Tuberous Sclerosis Complex: new criteria for diagnostic work-up and management.
AB  - Tuberous sclerosis complex (TSC) is a rare genetic multisystem disorder,
      characterized by predominantly benign tumors in potentially all organ systems.
      System involvement, severity of clinical symptoms and the response to treatment
      are age-dependent and heterogeneous. Consequently, the disorder is still not
      recognized in a considerable number of patients. The diagnostic criteria and the
      guidelines for surveillance and management of patients with TSC were revised, and
      the establishment of specialized TSC-centers was strongly recommended during an
      International Consensus Conference in 2012. TOSCA (TuberOus SClerosis registry to
      increase disease Awareness), an international patient registry, was started to
      allow new insights into the causes of different courses. Finally, there are-since
      the approval of the mTOR inhibitor Everolimus-promising new therapeutic
      approaches.This review focuses on the various TSC related symptoms occurring at
      different ages, the novel recommendations for diagnosis and treatment as well as
      the need for multidisciplinary follow-up.

PMID- 25860852
TI  - Treatment of hemorrhagic gastritis by Ankaferd blood stopper versus Omeprazole:
      experimental randomized rat models.
AB  - BACKGROUND: Ankaferd blood stopper (ABS) is a herbal extract that enhances
      mucosal healing. It has therapeutic potential in the management of external
      hemorrhage and controlling gastrointestinal bleeding associated with various
      benign lesions refractory to conventional antihemorrhagic measures. The aim of
      this experimental study was to assess the effects of ABS on hemorrhagic lesions
      and compare them with omeprazole. METHODS: The study was conducted on 30 rats.
      Rats were divided into five groups: group A (only indomethacin), group B (ABS
      administration 60 min before indomethacin-induced injury), group C (ABS
      administration 30 min after indomethacin-induced injury), group D (omeprazole
      administration 60 min before indomethacin-induced injury), group E (omeprazole
      administration 30 min after indomethacin-induced injury). Gastric mucosal lesions
      were produced by indomethacin in all three groups. The effect was studied
      morphologically 6 h after oral administration of the drug. Subsequently, affected
      tissue was examined histologically. RESULTS: Based on the number and the total
      size of hemorrhagic lesions, the hemorrhagic lesion scores were significantly
      better in Group C compared to other groups (p < 0.05). The hemorrhagic lesion
      score of Group B was significantly better than Group D and Group A (p < 0.05).
      Omeprazole groups (Group D, Group E) did not show significant improvement as
      indicated by macroscopic scores. There was no significant difference between the
      groups with respect to microscopic scores. CONCLUSION: These results indicate
      that ABS has a potent inhibitory action on indomethacin-induced gastric bleeding
      and mucosal lesions and it is useful in the treatment of acute gastric mucosal
      lesions.

PMID- 25860853
TI  - Killer-cell immunoglobulin-like receptor and human leukocyte antigen-C genes in
      common variable immunodeficiency.
AB  - BACKGROUND: We aimed herein to investigate the killer-cell immunoglobulin-like
      receptor (KIR) genes and human leukocyte antigen (HLA)-C alleles in patients with
      common variable immunodeficiency (CVID), and to reveal their differences from
      those in healthy population. METHODS: In all, 18 patients who have been diagnosed
      with CVID and 15 living donors of kidney transplant recipients were enrolled in
      the study. Polymerase chain reaction-sequence-specific primer (PCR-SSP) typing
      method was used in molecular genetic analysis. The frequencies of the genes in
      the study groups were statistically compared with each other using chi-square or
      Fisher exact tests, whichever were appropriate. RESULTS: Although there was no
      significant difference between both study groups with respect to distribution of
      KIR and HLA-C2 group genes, HLA-Cw7 allele frequency in patients with CVID was
      significantly lower than that in healthy population (P = 0.008). CONCLUSION: This
      present study results support that HLA-Cw7 allele, an inhibitor of KIR ligand,
      may play a role in the pathogenesis of CVID.

PMID- 25860855
TI  - Mechanical Tuning of LaAlO3/SrTiO3 Interface Conductivity.
AB  - In recent years, complex-oxide heterostructures and their interfaces have become
      the focus of significant research activity, primarily driven by the discovery of
      emerging states and functionalities that open up opportunities for the
      development of new oxide-based nanoelectronic devices. The highly conductive
      state at the interface between insulators LaAlO3 and SrTiO3 is a prime example of
      such emergent functionality, with potential application in high electron density
      transistors. In this report, we demonstrate a new paradigm for voltage-free
      tuning of LaAlO3/SrTiO3 (LAO/STO) interface conductivity, which involves the
      mechanical gating of interface conductance through stress exerted by the tip of a
      scanning probe microscope. The mechanical control of channel conductivity and the
      long retention time of the induced resistance states enable transistor
      functionality with zero gate voltage. 

PMID- 25860854
TI  - Experiences of community pharmacists advising pregnant women.
AB  - BACKGROUND: Recent studies have shown that pharmacists provide healthcare advice
      to pregnant women, and that they can play an important role in maternal care.
      However, pharmacists have faced challenges in advising mothers and coordinating
      with physicians. OBJECTIVE: To explore the experiences of community pharmacists
      in advising pregnant women at Lithuanian community pharmacies. SETTING: Community
      pharmacies in Lithuania. METHODS: Community pharmacists (n = 27) were recruited
      for semistructured face-to-face interviews from June 2012 to March 2013. A
      qualitative and descriptive study based on the content analysis approach was used
      for data collection and analysis. MAIN OUTCOME MEASURE: Thematic coding of
      Lithuanian community pharmacist interview content. RESULTS: Three main areas
      emerged: topics of advice-giving, provision of information, and barriers to
      advice-giving. The question of whether to interact with the physician connected
      to all of these areas. Pharmacists described different practices about the advice
      they gave and how they gave it. Lack of knowledge and skills, both about
      pregnancy and about patient-physician-pharmacist interaction, were a clear
      barrier to care for pregnant women in community pharmacies. CONCLUSION:
      Respondents were comfortable giving advice in clear situations, and found it
      challenging to do so otherwise. Improving the physician-pharmacist-patient
      communication environment and providing education and training programmes for
      pharmacists is necessary to reduce stress and to overcome barriers in advising
      pregnant women.

PMID- 25860856
TI  - Automated Speech Rate Measurement in Dysarthria.
AB  - PURPOSE: In this study, a new algorithm for automated determination of speech
      rate (SR) in dysarthric speech is evaluated. We investigated how reliably the
      algorithm calculates the SR of dysarthric speech samples when compared with
      calculation performed by speech-language pathologists. METHOD: The new algorithm
      was trained and tested using Dutch speech samples of 36 speakers with no history
      of speech impairment and 40 speakers with mild to moderate dysarthria. We tested
      the algorithm under various conditions: according to speech task type (sentence
      reading, passage reading, and storytelling) and algorithm optimization method
      (speaker group optimization and individual speaker optimization). Correlations
      between automated and human SR determination were calculated for each condition.
      RESULTS: High correlations between automated and human SR determination were
      found in the various testing conditions. CONCLUSIONS: The new algorithm measures
      SR in a sufficiently reliable manner. It is currently being integrated in a
      clinical software tool for assessing and managing prosody in dysarthric speech.
      Further research is needed to fine-tune the algorithm to severely dysarthric
      speech, to make the algorithm less sensitive to background noise, and to evaluate
      how the algorithm deals with syllabic consonants.

PMID- 25860857
TI  - Effects of combination between web density and size of spider mite on predation
      by a generalist and a specialist phytoseiid mite.
AB  - Complicated three-dimensional webs of silk threads produced by Tetranychus spider
      mites provide protection from predation by many generalist phytoseiid mite
      species. Accessibility to prey may be the most significant criterion for
      successful predation in complicated webs. To assess the protective effects of
      combination between web size and density, we compared predation on eggs of the
      two-spotted spider mite, Tetranychus urticae, by a generalist (Euseius sojaensis)
      and a specialist (Neoseiulus womersleyi) phytoseiid mite in the laboratory under
      manipulated web size and density. Web sizes negatively affected to the predation.
      Significant interactions were found between phytoseiid mite species and prey
      distribution; egg consumption by E. sojaensis was more in uniform distribution,
      but that by N. womersleyi, in contrast, was larger in contagious distribution.
      However, the egg consumption by E. sojaensis and N. womersleyi were both
      mitigated in larger webs. This area size depending mitigation was more effective
      to the predation by E. sojaensis. Although the mechanism of web size depending
      mitigation is unknown, web sizes might affect prey searching efficiency of this
      phytoseiid mite. Consequently, combination between web density and size are
      likely to affect not only a generalist E. sojaensis but also a specialist N.
      wormersleyi. 

PMID- 25860858
TI  - Diversity and population dynamics of Ascidae, Blattisociidae and Melicharidae
      (Acari: Mesostigmata) in tropical flowers in Brazil.
AB  - Cultivation of tropical flowers has expanded considerably in Brazil, justifying
      efforts to determine the arthropods associated with it. Heliconia species are
      some of the most important tropical flowers in Brazil. Mites of the families
      Ascidae, Blattisociidae and Melicharidae are commonly found on those plants. They
      disperse from flower to flower on hummingbirds. The objective of this study was
      to identify the diversity of mites of this group in tropical flowers, with
      emphasis on Heliconia species, in Brazil and to determine the fluctuation of the
      population of these mites in Piracicaba, Sao Paulo state. Specimens from
      Amazonas, Bahia, Pernambuco, Minas Gerais, Rio de Janeiro, Santa Catarina and Sao
      Paulo States were examined. Mites of the genera Asca and Iphidozercon (Ascidae),
      Cheiroseius and Lasioseius (Blattisociidae), and Proctolaelaps and Tropicoseius
      (Melicharidae) were collected in flowers of four plant families, with Lasioseius
      being the most diverse genus. Overall, most specimens found belonged to
      Tropicoseius, especially Tropicoseius venezuelensis Baker & Yunker; this was the
      dominant species on five of 13 Heliconia species/hybrids considered in this
      study. Samples of panicles of Heliconia rostrata Ruiz & Pavon were collected
      every 2 weeks, in Piracicaba. Six species of those mite families were found,
      among which Tropicoseius heliconiae Baker & Yunker and T. venezuelensis were the
      most numerous. The highest population levels of mites of those three families
      occurred at the beginning and at the end of the year, coinciding with the highest
      levels of rainfall, relative humidity and temperature, when plant flowers were
      most numerous and vigorous. Along each panicle, the highest mite densities were
      found in inflorescences of the three distal eighths of the panicles, where nectar
      and pollen were probably most abundant. 

PMID- 25860859
TI  - Phylogeny and species delineation in European species of the genus Steganacarus
      (Acari, Oribatida) using mitochondrial and nuclear markers.
AB  - Species of the genus Steganacarus are soil-living oribatid mites (Acari,
      Phthiracaridae) with a ptychoid body. The phylogeny and species status of the
      species of Steganacarus are not resolved, some authors group all ten German
      species of Steganacarus within the genus Steganacarus whereas others split them
      into three subgenera, Steganacarus, Tropacarus and Atropacarus. Additionally, two
      species, S. magnus and T. carinatus, comprise morphotypes of questionable species
      status. We investigated the phylogeny and species status of ten European
      Steganacarus species, i.e. S. applicatus, S. herculeanus, S. magnus forma magna,
      S. magnus forma anomala, S. spinosus, Tropacarus brevipilus, T. carinatus forma
      carinata, T. carinatus forma pulcherrima, Atropacarus striculus and Rhacaplacarus
      ortizi. We used two molecular markers, a 251 bp fragment of the nuclear gene 28S
      rDNA (D3) and a 477 bp fragment of the mitochondrial COI region. The phylogeny
      based on a combined analysis of D3 and COI separated four subgenera
      (Steganacarus, Tropacarus and Atropacarus, Rhacaplacarus) indicating that they
      form monophyletic groups. The COI region separated all ten species of the genus
      Steganacarus and showed variation within some species often correlating with the
      geographic origin of the species. Resolution of the more conserved D3 region was
      limited, indicating that radiation events are rather recent. Overall, our results
      indicate that both genes alone cannot be used for phylogeny and barcoding since
      variation is too low in D3 and too high in COI. However, when used in combination
      these genes provide reliable insight into the phylogeny, radiation and species
      status of taxa of the genus Steganacarus. 

PMID- 25860860
TI  - The effect of queen pheromone status on Varroa mite removal from honey bee
      colonies with different grooming ability.
AB  - The objective of this study was to assess the effects of honey bees (Apis
      mellifera L.) with different grooming ability and queen pheromone status on
      mortality rates of Varroa mites (Varroa destructor Anderson and Trueman), mite
      damage, and mortality rates of honey bees. Twenty-four small queenless colonies
      containing either stock selected for high rates of mite removal (n = 12) or
      unselected stock (n = 12) were maintained under constant darkness at 5  degrees
      C. Colonies were randomly assigned to be treated with one of three queen
      pheromone status treatments: (1) caged, mated queen, (2) a synthetic queen
      mandibular pheromone lure (QMP), or (3) queenless with no queen substitute. The
      results showed overall mite mortality rate was greater in stock selected for
      grooming than in unselected stock. There was a short term transitory increase in
      bee mortality rates in selected stock when compared to unselected stock. The
      presence of queen pheromone from either caged, mated queens or QMP enhanced mite
      removal from clusters of bees relative to queenless colonies over short periods
      of time and increased the variation in mite mortality over time relative to
      colonies without queen pheromone, but did not affect the proportion of damaged
      mites. The effects of source of bees on mite damage varied with time but damage
      to mites was not reliably related to mite mortality. In conclusion, this study
      showed differential mite removal of different stocks was possible under low
      temperature. Queen status should be considered when designing experiments using
      bioassays for grooming response.

PMID- 25860861
TI  - Sirt7 promotes gastric cancer growth and inhibits apoptosis by epigenetically
      inhibiting miR-34a.
AB  - Gastric cancer is the fourth most common cancer worldwide, with a low 5-year
      survival rate. Epigenetic modification plays pivotal roles in gastric cancer
      development. However, the role of histone-modifying enzymes in gastric cancer
      remains largely unknown. Here we report that Sirt7, a NAD(+)-dependent class III
      histone deacetylase, is over-expressed in human gastric cancer tissues. Sirt7
      level is significantly correlated with disease stage, metastasis, and survival.
      Knockdown of Sirt7 in gastric cancer cells inhibits cell proliferation and colony
      formation in vitro. In vivo subcutaneous xenograft results also show that Sirt7
      knockdown can markedly repress gastric cancer cell growth. In addition, Sirt7
      depletion induces apoptosis in gastric cancer cells via up-regulating expression
      of pro-apoptotic proteins and down-regulating anti-apoptotic proteins.
      Mechanically, Sirt7 binds to the promoter of miR-34a and deacetylases the
      H3K18ac, thus represses miR-34a expression. Reversely, depletion of miR-34a
      inhibits gastric cancer apoptosis induced by Sirt7 knockdown, and restores
      cellular capacity of proliferation and colony formation. miR-34a depletion
      reduces Sirt7-knockdown-induced arrest of gastric growth. Finally, miR-34a is
      tightly associated with survival of patients with gastric cancer. 

PMID- 25860862
TI  - Characteristic correlations of the structure-function relationship in different
      glaucomatous disc types.
AB  - PURPOSE: To investigate the influence of the optic disc type on the overall and
      regional correlation between structure and function in open angle glaucoma (OAG).
      METHODS: We divided 144 eyes of 144 patients with OAG into four groups according
      to Nicolela et al.'s classification of optic disc type: focal ischemic (FI),
      myopic glaucomatous (MY), senile sclerotic (SS), and generalized enlargement
      (GE). We measured the circumpapillary retinal nerve fiber layer thickness
      (cpRNFLT) with the 3D OCT-2000 and the mean deviation (MD) with the Humphrey
      Field Analyzer in each group and determined the influence of the disc type on
      these parameters with the Spearman rank correlation. RESULTS: We found that
      cpRNFLT and MD were significantly correlated in the MY (r = 0.61, P < 0.001), GE
      (r = 0.62, P < 0.001), and SS groups (r = 0.52, P = 0.002), but not in the FI
      group (r = 0.25, P = 0.130). The region of the optic disc with the highest
      correlation coefficient between structure and function differed according to the
      disc type. CONCLUSIONS: The correlation between cpRNFLT and MD varied according
      to the optic disc morphology in OAG. This suggests that different disc types have
      characteristic regional variations in the correlation between structure and
      function. The disc type should therefore be considered in investigations of the
      correlation between structure and function in glaucoma.

PMID- 25860864
TI  - Age-related change in gammaH2AX of Drosophila muscle: its significance as a
      marker for muscle damage and longevity.
AB  - Muscle aging is closely related to unhealthy late-life and organismal aging.
      Recently, the state of differentiated cells was shown to be critical to tissue
      homeostasis. Thus, understanding how fully differentiated muscle cells age is
      required for ensuring healthy aging. Adult Drosophila muscle is a useful model
      for exploring the aging process of fully differentiated cells. In this study, we
      investigated age-related changes of gammaH2AX, an indicator of DNA strand breaks,
      in adult Drosophila muscle to document whether its changes are correlated with
      muscle degeneration and lifespan. The results demonstrate that gammaH2AX
      accumulation increases in adult Drosophila thoracic and leg muscles with age.
      Analyses of short-, normal-, and long-lived strains indicate that the age-related
      increase of gammaH2AX is closely associated with the extent of muscle
      degeneration, cleaved caspase-3 and poly-ubiquitin aggregates, and longevity.
      Further analysis of muscle-specific knockdown of heterochromatin protein 1a
      revealed that the excessive gammaH2AX accumulation in thoracic and leg muscles
      induces accelerated degeneration and decreases longevity. These data suggest a
      strong correlation between age-related muscle damage and lifespan in Drosophila.
      Our findings indicate that gammaH2AX may be a reliable biomarker for assessing
      muscle aging in Drosophila. 

PMID- 25860865
TI  - The value of red blood cell distribution width in endometrial cancer.
AB  - BACKGROUND: Red cell distribution width (RDW) is a routinely examined parameter
      with the complete blood count. In recent studies, RDW levels have been associated
      with cardiovascular, liver and renal diseases and solid tumors. The aim of this
      study was to evaluate the alterations of RDW levels in benign and malignant
      causes of postmenopausal bleeding and to investigate the association of RDW
      levels with clinicopathological parameters of endometrial cancer (EC) patients.
      METHODS: A retrospective study was made of a total of 884 females who were
      admitted to hospital for postmenopausal bleeding between May 2009 and December
      2013. After inclusion and exclusion criteria were applied, 222 patients remained.
      Complete blood count data was obtained from the recorded computerized database.
      After pathological evaluation, the patients were divided into two groups, benign
      and malignant (EC). RESULTS: The EC group (n=113) had significantly higher RDW
      levels compared to the benign group (14.78+/-2.02 vs. 13.88+/-1.05; p=0.000).
      Grade II and above EC patients had higher levels of RDW than Grade I patients
      (15.2+/-2.3 vs. 14.1+/-1.00; p=0.005). Correlation analyses also revealed a
      negative correlation between RDW and hemoglobin levels (p=0.000), RDW and mean
      corpuscular volume (p=0.000), RDW and lymphocyte count (p=0.035) but a positive
      correlation between RDW and platelet to lymphocyte ratio (p=0.030). CONCLUSIONS:
      The results of the current study revealed the potential predicitve role of RDW in
      patients with postmenopausal bleeding. Significant associations were also
      determined between RDW and clinicopathological characteristics in EC patients.

PMID- 25860866
TI  - Effects of team-based learning on self-regulated online learning.
AB  - Online learning requires higher levels of self-regulation in order to achieve
      optimal learning outcomes. As nursing education moves further into the blended
      and online learning venue, new teaching/learning strategies will be required to
      develop and enhance self-regulated learning skills in nursing students. The
      purpose of this study was to compare the effectiveness of team-based learning
      (TBL) with traditional instructor-led (IL) learning, on self-regulated online
      learning outcomes, in a blended undergraduate research and evidence-based
      practice course. The nonrandomized sample consisted of 98 students enrolled in
      the IL control group and 86 students enrolled in the TBL intervention group. The
      percentage of total possible online viewing time was used as the measure of self
      regulated online learning activity. The TBL group demonstrated a significantly
      higher percentage (p < 0.001) of self-regulated learning activities than the IL
      control group. The TBL group scored significantly higher on the course
      examinations (p = 0.003). The findings indicate that TBL is an effective
      instructional strategy that can be used to achieve the essential outcomes of
      baccalaureate nursing education by increasing self-regulated learning
      capabilities in nursing students. 

PMID- 25860863
TI  - The influence of dietary fat source on liver and skeletal muscle mitochondrial
      modifications and lifespan changes in calorie-restricted mice.
AB  - The Membrane Theory of Aging proposes that lifespan is inversely related to the
      level of unsaturation in membrane phospholipids. Calorie restriction (CR) without
      malnutrition extends lifespan in many model organisms, which may be related to
      alterations in membrane phospholipids fatty acids. During the last few years our
      research focused on studying how altering the predominant fat source affects the
      outcome of CR in mice. We have established four dietary groups: one control group
      fed 95 % of a pre-determined ad libitum intake (in order to prevent obesity), and
      three CR groups fed 40 % less than ad libitum intake. Lipid source for the
      control and one of the CR groups was soybean oil (high in n-6 PUFA) whereas the
      two remaining CR groups were fed diets containing fish oil (high in n-3 PUFA), or
      lard (high in saturated and monounsaturated fatty acids). Dietary intervention
      periods ranged from 1 to 18 months. We performed a longitudinal lifespan study
      and a cross-sectional study set up to evaluate several mitochondrial parameters
      which included fatty acid composition, H(+) leak, activities of electron
      transport chain enzymes, ROS generation, lipid peroxidation, mitochondrial
      ultrastructure, and mitochondrial apoptotic signaling in liver and skeletal
      muscle. These approaches applied to different cohorts of mice have independently
      indicated that lard as a fat source often maximizes the effects of 40 % CR on
      mice. These effects could be due to significant increases of monounsaturated
      fatty acids levels, in accordance with the Membrane Theory of Aging. 

PMID- 25860867
TI  - Biological Activities and Identification of Bioactive Metabolite from Endophytic
      Aspergillus flavus L7 Isolated from Aegle marmelos.
AB  - Aegle marmelos, a well-known Indian plant with medicinal and religious
      importance, has been extensively used in Indian traditional medicine. The present
      study aimed to isolate, identify, and evaluate the biological activities of
      endophytic fungi from A. marmelos. One of the isolates, labeled as L7, was
      identified as Aspergillus flavus using morphology and ITS gene sequence. Total
      phenolic and flavonoid contents in the culture filtrate were found to be 65.77 mg
      GAE/ml and 158.33 mg quercetin/ml of crude extract, respectively. The extract
      showed excellent antimicrobial activity against common human bacterial and fungal
      pathogens. The test extract at 700 ug/ml, which notably reduced the concentration
      of DPPH-free radical as percent DPPH scavenging activity, was found to be the
      highest (64.53 %). The extract, at the concentration of 2 mg/ml, produced 70 %
      inhibition of hemolysis of RBCs compared to 78 % produced by standard drug
      (Ibuprofen). Chemical profiling of the fermented extract using TLC followed by UV
      and FTIR revealed the presence of flavonoids. The HPLC analysis confirmed the
      presence of bioflavonoid rutin in the extract. To the best of our knowledge, this
      is the first report on production of bioactive flavonoid by endophytic
      Aspergillus flavus obtained from A. marmelos and its pharmaceutical potential. In
      conclusion, the endophytic Aspergillus flavus obtained from the A. marmelos could
      be explored as an economic and potential natural resource with diverse
      pharmaceutical and biological activities. 

PMID- 25860868
TI  - The highest melting point challenge.

PMID- 25860869
TI  - Solution to the left-handed DNA challenge.

PMID- 25860870
TI  - An ecosystem-service approach to evaluate the role of non-native species in
      urbanized wetlands.
AB  - Natural wetlands have been increasingly transformed into urbanized ecosystems
      commonly colonized by stress-tolerant non-native species. Although non-native
      species present numerous threats to natural ecosystems, some could provide
      important benefits to urbanized ecosystems. This study investigated the extent of
      colonization by non-native fish and bird species of three urbanized wetlands in
      subtropical Taiwan. Using literature data the role of each non-native species in
      the urbanized wetland was evaluated by their effect (benefits/damages) on
      ecosystem services (ES) based on their ecological traits. Our sites were
      seriously colonized by non-native fishes (39%-100%), but <3% by non-native birds.
      Although most non-native species could damage ES regulation (disease control and
      wastewater purification), some could be beneficial to the urbanized wetland ES.
      Our results indicated the importance of non-native fishes in supporting ES by
      serving as food source to fish-eating waterbirds (native, and migratory species)
      due to their high abundance, particularly for Oreochromis spp. However, all non
      native birds are regarded as "harmful" species causing important ecosystem
      disservices, and thus eradication of these bird-invaders from urban wetlands
      would be needed. This simple framework for role evaluation of non-native species
      represents a holistic and transferable approach to facilitate decision making on
      management priority of non-native species in urbanized wetlands. 

PMID- 25860871
TI  - Antiviral activity and possible mechanism of action of constituents identified in
      Paeonia lactiflora root toward human rhinoviruses.
AB  - Human rhinoviruses (HRVs) are responsible for more than half of all cases of the
      common cold and cost billions of USD annually in medical visits and missed school
      and work. An assessment was made of the antiviral activities and mechanisms of
      action of paeonol (PA) and 1,2,3,4,6-penta-O-galloyl-beta-D-glucopyranose (PGG)
      from Paeonia lactiflora root toward HRV-2 and HRV-4 in MRC5 cells using a
      tetrazolium method and real-time quantitative reverse transcription polymerase
      chain reaction and enzyme-linked immunosorbent assay. Results were compared with
      those of a reference control ribavirin. Based on 50% inhibitory concentration
      values, PGG was 13.4 and 18.0 times more active toward HRV-2 (17.89 MUM) and HRV
      4 (17.33 MUM) in MRC5 cells, respectively, than ribavirin. The constituents had
      relatively high selective index values (3.3->8.5). The 100 MUg/mL PA and 20
      MUg/mL PGG did not interact with the HRV-4 particles. These constituents
      inhibited HRV-4 infection only when they were added during the virus inoculation
      (0 h), the adsorption period of HRVs, but not after 1 h or later. Moreover, the
      RNA replication levels of HRVs were remarkably reduced in the MRC5 cultures
      treated with these constituents. These findings suggest that PGG and PA may block
      or reduce the entry of the viruses into the cells to protect the cells from the
      virus destruction and abate virus replication, which may play an important role
      in interfering with expressions of rhinovirus receptors (intercellular adhesion
      molecule-1 and low-density lipoprotein receptor), inflammatory cytokines
      (interleukin (IL)-6, IL-8, tumor necrosis factor, interferon beta, and IL-1beta),
      and Toll-like receptor, which resulted in diminishing symptoms induced by HRV.
      Global efforts to reduce the level of synthetic drugs justify further studies on
      P. lactiflora root-derived materials as potential anti-HRV products or lead
      molecules for the prevention or treatment of HRV. 

PMID- 25860872
TI  - MicroRNA-like small RNAs prediction in the development of Antrodia cinnamomea.
AB  - Antrodia cinnamomea, a precious, host-specific brown-rot fungus that has been
      used as a folk medicine in Taiwan for centuries is known to have diverse
      bioactive compounds with potent pharmaceutical activity. In this study, different
      fermentation states of A. cinnamomea (wild-type fruiting bodies and liquid
      cultured mycelium) were sequenced using the next-generation sequencing (NGS)
      technique. A 45.58 Mb genome encoding 6,522 predicted genes was obtained. High
      quality reads were assembled into a total of 13,109 unigenes. Using a previously
      constructed pipeline to search for microRNAs (miRNAs), we then identified 4
      predicted conserved miRNA and 63 novel predicted miRNA-like small RNA (milRNA)
      candidates. Target prediction revealed several interesting proteins involved in
      tri-terpenoid synthesis, mating type recognition, chemical or physical sensory
      protein and transporters predicted to be regulated by the miRNAs and milRNAs. 

PMID- 25860873
TI  - Measurement of Choroidal Thickness Following Caffeine Intake in Healthy Subjects.
AB  - PURPOSE: The aim of this study is to investigate the effect of 200 mg caffeine on
      subfoveal choroidal thickness (CT) in the macular area as measured by enhanced
      depth imaging optical coherence tomography (EDI-OCT) in healthy subjects.
      MATERIALS AND METHODS: Fifty healthy individuals (study group) and 50 healthy
      individuals (control group) were enrolled in study. In the study group,
      participants received a 200 mg caffeine capsule and the control group consisted
      of subjects who received plasebo capsule. The subfoveal CT was measured by EDI
      OCT before the caffeine intake and at 30 min, 1 h, 2 h, 3 h, 4 h and 6 h
      following caffeine intake. RESULTS: SFCT after caffeine intake was significantly
      decreased at 30 min, 1 h, 2 h, 3 h and 4 h compared to the baseline measurement,
      while the difference between baseline and 6 h was not statistically significant
      in the study group. There were no significant differences between the baseline
      and the other measurement times in the control group (p > 0.05). CONCLUSION: The
      thinning of CT begins about 30 min after the oral ingestion of 200 mg of caffeine
      and lasts for about four hours.

PMID- 25860874
TI  - Self-Assembled Nanocube-Based Plasmene Nanosheets as Soft Surface-Enhanced Raman
      Scattering Substrates toward Direct Quantitative Drug Identification on Surfaces.
AB  - We report on self-assembled nanocube-based plasmene nanosheets as new surface
      enhanced Raman scattering (SERS) substrates toward direct identification of a
      trace amount of drugs sitting on topologically complex real-world surfaces. The
      uniform nanocube arrays (superlattices) led to low spatial SERS signal variances
      (~2%). Unlike conventional SERS substrates which are based on rigid
      nanostructured metals, our plasmene nanosheets are mechanically soft and
      optically semitransparent, enabling conformal attachment to real-world solid
      surfaces such as banknotes for direct SERS identification of drugs. Our plasmene
      nanosheets were able to detect benzocaine overdose down to a parts-per-billion
      (ppb) level with an excellent linear relationship (R(2) > 0.99) between
      characteristic peak intensity and concentration. On banknote surfaces, a
      detection limit of ~0.9 * 10(-6) g/cm(2) benzocaine could be achieved.
      Furthermore, a few other drugs could also be identified, even in their binary
      mixtures with our plasmene nanosheets. Our experimental results clearly show that
      our plasmene sheets represent a new class of unique SERS substrates, potentially
      serving as a versatile platform for real-world forensic drug identification. 

PMID- 25860875
TI  - alpha-Actinin-4 enhances colorectal cancer cell invasion by suppressing focal
      adhesion maturation.
AB  - alpha-Actinins (ACTNs) are known to crosslink actin filaments at focal adhesions
      in migrating cells. Among the four isoforms of mammalian ACTNs, ACTN1 and ACTN4
      are ubiquitously expressed. Recently, ACTN4 was reported to enhance cancer cell
      motility, invasion, and metastasis. However, the mechanism by which ACTN4 drives
      these malignant phenotypes remains unclear. Here, we show that ACTN4, but not
      ACTN1, induces the formation of immature focal adhesions in DLD-1 cells, leading
      to the rapid turnover of focal adhesions. Interestingly, zyxin (ZYX) assembly to
      focal adhesions was markedly decreased in ACTN4-expressing DLD-1 cells, while the
      recruitment of paxillin (PAX) occurred normally. On the other hand, in ACTN1
      expressing DLD-1 cells, PAX and ZYX were normally recruited to focal adhesions,
      suggesting that ACTN4 specifically impairs focal adhesion maturation by
      inhibiting the recruitment of ZYX to focal complexes. Using purified recombinant
      proteins, we found that ZYX binding to ACTN4 was defective under conditions where
      ZYX binding to ACTN1 was observed. Furthermore, Matrigel invasion of SW480 cells
      that express high endogenous levels of ACTN4 protein was inhibited by ectopic
      expression of ACTN1. Altogether, our results suggest that ZYX defective binding
      to ACTN4, which occupies focal adhesions instead of ACTN1, induces the formation
      of immature focal adhesions, resulting in the enhancement of cell motility and
      invasion. 

PMID- 25860876
TI  - Preserved Expression of mRNA Coding von Willebrand Factor-Cleaving Protease
      ADAMTS13 by Selenite and Activated Protein C.
AB  - In sepsis, the severity-dependent decrease of von Willebrand factor (VWF)
      inactivating protease, a disintegrin and metalloproteinase with thrombospondin
      motifs 13 (ADAMTS13), results in platelet aggregation and consumption, leading to
      sepsis-associated thrombotic microangiopathy (TMA) and organ failure. Previous
      reports assessing its functional deficiency have pinpointed involvement of
      autoantibodies or mutations to propagate thrombotic thrombocytopenic purpura
      (TTP). However, mechanisms of acquired ADAMTS13 deficiency during host response
      remain unclear. To enhance understanding of ADAMTS13 deficiency in sepsis, we
      evaluated changes in expression of mRNA coding ADAMTS13 during septic conditions
      using primary cellular sources of the protease. We hypothesized that
      proinflammatory cytokines and constituents of serum from septic patients affect
      the transcriptional level of ADAMTS13 in vitro, and previously recommended
      therapeutic agents as adjunctive therapy for sepsis interact therewith. Cultured
      hepatic stellate cells (HSCs), endothelial cells (HMEC) and human precision-cut
      liver slices as an ex vivo model were stimulated with sepsis prototypic
      cytokines, bacterial endotoxin and pooled serum obtained from septic patients.
      Stimulation resulted in a significant decrease in ADAMTS13 mRNA between 10% and
      80% of basal transcriptional rates. Costimulation of selenite or recombinant
      activated protein C (APC) with serum prevented ADAMTS13 decrease in HSCs and
      increased ADAMTS13 transcripts in HMEC. In archived clinical samples, the
      activity of ADAMTS13 in septic patients treated with APC (n = 5) increased with
      an accompanying decrease in VWF propeptide as surrogate for improved endothelial
      function. In conclusion, proinflammatory conditions of sepsis repress mRNA coding
      ADAMTS13 and the ameliorating effect by selenite and APC may support the concept
      for identification of beneficial mechanisms triggered by these drugs at a
      molecular level. 

PMID- 25860878
TI  - Doctor shopping for medications used in the treatment of attention deficit
      hyperactivity disorder: shoppers often pay in cash and cross state lines.
AB  - BACKGROUND: Doctor shopping, defined by filling overlapping prescriptions from
      more than one prescriber at more than two pharmacies, is a way to obtain
      scheduled medications for diversion or abuse. Little is known about how far
      attention deficit hyperactivity disorder (ADHD) medication shoppers travel, how
      often they cross state lines to fill their ADHD prescriptions and how often they
      pay for their medication in cash, i.e. entirely out of pocket. OBJECTIVE: We
      sought to describe the pattern of doctor shopping for ADHD medications: how far
      shoppers travel, how often they cross state lines to fill their prescriptions,
      and how often they pay in cash. METHODS: Retrospective cohort study using LRx, a
      large US retail prescription database. We included subjects with any ADHD
      medication dispensed between 2011 and 2012. Subjects were followed for 18 months.
      RESULTS: Of a total of 4 402 464 subjects exposed to ADHD medications, 0.4%
      developed shopping behavior. Women were more likely to become shoppers. Shoppers
      travelled a median of 91.9 miles and non-shoppers 0.2 miles to fill their ADHD
      prescriptions. Almost 28% of the shoppers filled prescriptions in >1 state
      compared with 4.3% of non-shoppers. Of the shoppers, 27.3% paid at least one
      prescription in cash compared to 14.4% of the non-shoppers. CONCLUSIONS: Shoppers
      travelled larger distances, visited more states and paid in cash for ADHD
      medications more often than non-shoppers. Data sharing among prescriptions
      monitoring programs can improve their effectiveness and drug utilization studies
      should take account of cash purchases.

PMID- 25860879
TI  - Hygroscopicity of Mixed Glycerol/Mg(NO3)2/Water Droplets Affected by the
      Interaction between Magnesium Ions and Glycerol Molecules.
AB  - Tropospheric aerosols are usually complex mixtures of inorganic and organic
      components, which can influence the hygroscopicities of each other. In this
      research, we applied confocal Raman technology combined with optical microscopy
      to investigate the relationship between the hygroscopic behavior and the
      molecular interactions of mixed glycerol/Mg(NO3)2/water droplets. Raman spectra
      provide detailed structural information about the interactions between glycerol
      molecules and Mg(2+) ions, as well as information about the interactions between
      glycerol and NO3(-) ions through electrostatic interaction and hydrogen bonding.
      The change of the CH2 stretching band of glycerol molecules in mixed droplets
      suggests that the backbone structures of glycerol mainly transform from
      alphaalpha to gammagamma in the dehumidifying process, and the additional Mg(2+)
      ions strongly influence the structure of glycerol molecules. Because the
      existence of glycerol suppresses the crystallization of Mg(NO3)2.6H2O in the
      dehumidifying process, Mg(NO3)2 molecules in mixed droplets form an amorphous
      state rather than forming crystals of Mg(NO3)2.6H2O when the relative humidity is
      lower than 17.8%. Moreover, in mixed droplets, the molar ratio of NO3(-) to
      glycerol is higher in the center than in the outer region. 

PMID- 25860877
TI  - A Human-Specific alpha7-Nicotinic Acetylcholine Receptor Gene in Human
      Leukocytes: Identification, Regulation and the Consequences of CHRFAM7A
      Expression.
AB  - The human genome contains a variant form of the alpha7-nicotinic acetylcholine
      receptor (alpha7nAChR) gene that is uniquely human. This CHRFAM7A gene arose
      during human speciation and recent data suggests that its expression alters
      ligand tropism of the normally homopentameric human alpha7-AChR ligand-gated cell
      surface ion channel that is found on the surface of many different cell types. To
      understand its possible significance in regulating inflammation in humans, we
      investigated its expression in normal human leukocytes and leukocyte cell lines,
      compared CHRFAM7A expression to that of the CHRNA7 gene, mapped its promoter and
      characterized the effects of stable CHRFAM7A overexpression. We report here that
      CHRFAM7A is highly expressed in human leukocytes but that the levels of both
      CHRFAM7A and CHRNA7 mRNAs were independent and varied widely. To this end,
      mapping of the CHRFAM7A promoter in its 5'-untranslated region (UTR) identified a
      unique 1-kb sequence that independently regulates CHRFAM7A gene expression.
      Because overexpression of CHRFAM7A in THP1 cells altered the cell phenotype and
      modified the expression of genes associated with focal adhesion (for example,
      FAK, P13K, Akt, rho, GEF, Elk1, CycD), leukocyte transepithelial migration (Nox,
      ITG, MMPs, PKC) and cancer (kit, kitL, ras, cFos cyclinD1, Frizzled and GPCR), we
      conclude that CHRFAM7A is biologically active. Most surprisingly however, stable
      CHRFAM7A overexpression in THP1 cells upregulated CHRNA7, which, in turn, led to
      increased binding of the specific alpha7nAChR ligand, bungarotoxin, on the THP1
      cell surface. Taken together, these data confirm the close association between
      CHRFAM7A and CHRNA7 expression, establish a biological consequence to CHRFAM7A
      expression in human leukocytes and support the possibility that this human
      specific gene might contribute to, and/or gauge, a human-specific response to
      inflammation. 

PMID- 25860880
TI  - The correlation of intramuscular fat content between muscles of the lamb carcass
      and the use of computed tomography to predict intramuscular fat percentage in
      lambs.
AB  - Intramuscular fat (IMF) % contributes positively to the juiciness and flavour of
      lamb and is therefore a useful indicator of eating quality. A rapid, non
      destructive method of IMF determination like computed tomography (CT) would
      enable pre-sorting of carcasses based on IMF% and potential eating quality. Given
      the loin muscle (longissimus lumborum) is easy to sample, a single measurement at
      this site would be useful, providing is correlates well to other muscles. To
      determine the ability of CT to predict IMF%, this study used 400 animals and
      examined 5 muscles from three sections of the carcass: from the fore-section the
      m. supraspinatus and m. infraspinatus, from the saddle-section the m. longissimus
      lumborum and from the hind-section the m. semimembranosus and m. semitendinosus.
      The average CT pixel density of muscle was negatively associated with IMF% and
      can be used to predict IMF% although precision in this study was poor. The
      ability of CT to predict IMF% was greatest in the m. longissimus lumborum (slope 
      0.07) and smallest in the m. infraspinatus (slope -0.02). The correlation
      coefficients of IMF% between the five muscles were variable, with the highest
      correlation coefficients evident between muscles of the fore section (0.67
      between the m. supraspinatus and the m. infraspinatus) and the weakest
      correlations were between the muscle of the fore and hind section. The
      correlation between the m. longissimus lumborum to the other muscles was fairly
      consistent with values ranging between 0.34 and 0.40 (partial correlation
      coefficient). The correlation between the proportion of carcass fat and the IMF%
      of the five muscles varied and was greatest in the m. longissimus lumborum
      (0.41). 

PMID- 25860881
TI  - Human identification through the analysis of smile photographs.
AB  - The comparison between antemortem and portmortem data comprehends the basis of
      the dental identification process. High-tech devices allow for optimal
      manipulation of postmortem data. However, in especial situations, the victims do
      not have records of dental treatments, making necessary the search for antemortem
      data from personal belongings. Smile photographs are one of the most common
      sources of dental information detected from personal belongings. In this context,
      the present study reports a forensic case in which a charred body was positively
      identified through the application of 3 techniques for the analysis of smile
      photographs. 

PMID- 25860882
TI  - Correction: Proteomic analysis of urine exosomes reveals renal tubule response to
      leptospiral colonization in experimentally infected rats.

PMID- 25860883
TI  - Correction: Genetic analysis of membrane cofactor protein (CD46) of the
      complement system in women with and without preeclamptic pregnancies.

PMID- 25860884
TI  - SiRNA-induced mutation in HIV-1 polypurine tract region and its influence on
      viral fitness.
AB  - Converting single-stranded viral RNA into double stranded DNA for integration is
      an essential step in HIV-1 replication. Initial polymerization of minus-strand
      DNA is primed from a host derived tRNA, whereas subsequent plus-strand synthesis
      requires viral primers derived from the 3' and central polypurine tracts (3' and
      cPPTs). The 5' and 3' termini of these conserved RNA sequence elements are
      precisely cleaved by RT-associated RNase H to generate specific primers that are
      used to initiate plus-strand DNA synthesis. In this study, siRNA wad used to
      produce a replicative HIV-1 variant contained G(-1)A and T(-16)A substitutions
      within/adjacent to the 3'PPT sequence. Introducing either or both mutations into
      the 3'PPT region or only the G(-1)A substitution in the cPPT region of NL4-3
      produced infectious virus with decreased fitness relative to the wild-type virus.
      In contrast, introducing the T(-16)A or both mutations into the cPPT rendered the
      virus(es) incapable of replication, most likely due to the F185L integrase
      mutation produced by this nucleotide substitution. Finally, the effects of G(-1)A
      and T(-16)A mutations on cleavage of the 3'PPT were examined using an in vitro
      RNase H cleavage assay. Substrate containing both mutations was mis-cleaved to a
      greater extent than either wild-type substrate or substrate containing the T(
      16)A mutation alone, which is consistent with the observed effects of the
      equivalent nucleotide substitutions on the replication fitness of NL4-3 virus. In
      conclusion, siRNA targeting of the HIV-1 3'PPT region can substantially suppress
      virus replication, and this selective pressure can be used to generate infectious
      virus containing mutations within or near the HIV-1 PPT. Moreover, in-depth
      analysis of the resistance mutations demonstrates that although virus containing
      a G(-1)A mutation within the 3'PPT is capable of replication, this nucleotide
      substitution shifts the 3'-terminal cleavage site in the 3'PPT by one nucleotide
      (nt) and significantly reduces viral fitness. 

PMID- 25860886
TI  - Trimodal (18)F-DOPA PET/CT/MR fusion imaging for optimal restaging of head and
      neck paragangliomas in a SDHD mutation carrier.

PMID- 25860885
TI  - Serum albumin is associated with peripheral nerve function in patients with type
      2 diabetes.
AB  - The aim of this study is to investigate the association between serum albumin
      concentrations and nerve conduction (NC) parameters in Chinese patients with type
      2 diabetes (T2DM). A total of 409 T2DM patients were enrolled between October
      2010 and April 2014. All participants underwent nerve conduction studies. The
      composite Z scores for NC parameters including conduction velocity (CV),
      amplitude, and latency were calculated as well. Serum albumin was measured by
      Bromcresol Green dye-binding method. The composite Z scores of CV and amplitude
      increased with the increasing albumin tertiles (test for trend, both P < 0.001),
      while the composite Z score of latency decreased with increasing albumin tertiles
      (test for trend, P < 0.001). After adjusting for age, sex, duration, and HbA1c,
      higher serum albumin concentrations were associated with higher composite Z
      scores of CV (beta = 0.314, P < 0.001), amplitude (beta = 0.279, P < 0.001), and
      lower composite Z score of latency (beta = -0.279, P < 0.001). When participants
      were stratified into albuminuria and normoalbuminuria group, we found the
      associations of serum albumin with composite Z scores of NC parameters remained
      significant only in the albuminuria group (CV Z score: beta = 0.253, P = 0.002;
      amplitude Z score: beta = 0.233, P = 0.006; latency Z score: beta = -0.217 P =
      0.013) after further adjustment for urinary albumin to creatinine ratio. The
      optimal cutoff point of serum albumin to indicate abnormal peripheral nerve
      function was 36.75 g/L in T2DM patients with albuminuria, with a sensitivity of
      65.6 % and a specificity of 78.0 %. Serum albumin was independently associated
      with peripheral nerve function in T2DM patients, especially in those with
      albuminuria. Serum albumin could be a potential biomarker for diabetic peripheral
      neuropathy. 

PMID- 25860887
TI  - Bmp6 expression in murine liver non parenchymal cells: a mechanism to control
      their high iron exporter activity and protect hepatocytes from iron overload?
AB  - Bmp6 is the main activator of hepcidin, the liver hormone that negatively
      regulates plasma iron influx by degrading the sole iron exporter ferroportin in
      enterocytes and macrophages. Bmp6 expression is modulated by iron but the
      molecular mechanisms are unknown. Although hepcidin is expressed almost
      exclusively by hepatocytes (HCs), Bmp6 is produced also by non-parenchymal cells
      (NPCs), mainly sinusoidal endothelial cells (LSECs). To investigate the
      regulation of Bmp6 in HCs and NPCs, liver cells were isolated from adult wild
      type mice whose diet was modified in iron content in acute or chronic manner and
      in disease models of iron deficiency (Tmprss6 KO mouse) and overload (Hjv KO
      mouse). With manipulation of dietary iron in wild-type mice, Bmp6 and Tfr1
      expression in both HCs and NPCs was inversely related, as expected. When hepcidin
      expression is abnormal in murine models of iron overload (Hjv KO mice) and
      deficiency (Tmprss6 KO mice), Bmp6 expression in NPCs was not related to Tfr1.
      Despite the low Bmp6 in NPCs from Tmprss6 KO mice, Tfr1 mRNA was also low.
      Conversely, despite body iron overload and high expression of Bmp6 in NPCs from
      Hjv KO mice, Tfr1 mRNA and protein were increased. However, in the same cells
      ferritin L was only slightly increased, but the iron content was not, suggesting
      that Bmp6 in these cells reflects the high intracellular iron import and export.
      We propose that NPCs, sensing the iron flux, not only increase hepcidin through
      Bmp6 with a paracrine mechanism to control systemic iron homeostasis but,
      controlling hepcidin, they regulate their own ferroportin, inducing iron
      retention or release and further modulating Bmp6 production in an autocrine
      manner. This mechanism, that contributes to protect HC from iron loading or
      deficiency, is lost in disease models of hepcidin production. 

PMID- 25860888
TI  - The predictive value of serum squamous cell carcinoma antigen in patients with
      cervical cancer who receive neoadjuvant chemotherapy followed by radical surgery:
      a single-institute study.
AB  - OBJECTIVE: Neoadjuvant chemotherapy (NACT) could affect the levels of squamous
      cell carcinoma antigen (SCC-Ag). This study evaluates the predictive value of pre
      and posttreatment SCC-Ag levels in patients with cervical cancer who were
      treated with NACT followed by radical surgery. METHODS: A total of 286 patients
      with Stage IB1-IIIB squamous cell carcinoma of the uterine cervix who were
      treated with NACT followed by radical hysterectomy were analyzed retrospectively.
      The relationship between SCC-Ag levels, the clinicopathologic parameters, the
      response to NACT and the three-year survival rate was investigated. RESULTS: The
      levels of SCC-Ag were elevated (>3.5 ng/mL) in 43.8% of patients before NACT, and
      13.0% of patients after NACT. Pre- and posttreatment levels of SCC-Ag correlated
      with the response to NACT (P = 0.010, and P<0.001), deep stromal infiltration (P
      = 0.041, and P = 0.006), and lymph node status (P<0.001, and P<0.001). In the
      multivariate analysis, the elevated pretreatment level of SCC-Ag was demonstrated
      to be an independent risk factor for Lymph node metastases (P<0.001). Patients
      with both pre- and posttreatment SCC-Ag levels <=3.5 ng/mL showed the best 3-year
      disease-free survival (DFS) and 3-year overall survival (OS) compared with
      patients with either pre- or posttreatment levels >3.5 ng/mL (P<0.001, and
      P<0.001, respectively). A multivariate analysis showed that posttreatment SCC-Ag
      levels were a strong independent predictor of OS (P = 0.001) and DFS (P = 0.012).
      CONCLUSION: Elevated pretreatment levels of SCC-Ag (>3.5 ng/mL) indicated a poor
      response to NACT and a higher risk of lymph node metastases. Elevated
      posttreatment levels of SCC-Ag were correlated with poor DFS and OS.

PMID- 25860889
TI  - Better One-Eyed than Blind--Challenges and Opportunities of Biomass Measurement
      During Solid-State Fermentation of Basidiomycetes.
AB  - Filamentous fungi, especially basidiomycetes, produce a wide range of
      metabolites, many of which have potential biotechnological and industrial
      applications. Solid-state fermentation (SSF) is very suitable for the cultivation
      of basidiomycetes since it mimics the natural habitat of these fungi. Some of the
      major advantages of SSF are the robustness of the process, the use of low-cost
      residual materials as substrates, and the reduced usage of water. However,
      monitoring key variables is difficult, which makes process control a challenge.
      Specifically, it is very difficult to determine the biomass during SSF process
      involving basidiomycetes. This is problematic, as the biomass is normally a key
      variable in mass and energy balance equations. Further, the success of fungal SSF
      processes is often evaluated, in part, based on the growth of the fungus. Direct
      determination of the dry weight of biomass is impossible and indirect
      quantification techniques must be used. Over the years, various determination
      techniques have been developed for the quantification of fungal biomass in SSF
      processes. The current review gives an overview of various direct and indirect
      biomass determination methods, discussing their advantages and disadvantages.

PMID- 25860890
TI  - Acceleration of vascular sprouting from fabricated perfusable vascular-like
      structures.
AB  - Fabrication of vascular networks is essential for engineering three-dimensional
      thick tissues and organs in the emerging fields of tissue engineering and
      regenerative medicine. In this study, we describe the fabrication of perfusable
      vascular-like structures by transferring endothelial cells using an
      electrochemical reaction as well as acceleration of subsequent endothelial
      sprouting by two stimuli: phorbol 12-myristate 13-acetate (PMA) and fluidic shear
      stress. The electrochemical transfer of cells was achieved using an oligopeptide
      that formed a dense molecular layer on a gold surface and was then
      electrochemically desorbed from the surface. Human umbilical vein endothelial
      cells (HUVECs), adhered to gold-coated needles (phi600 MUm) via the oligopeptide,
      were transferred to collagen gel along with electrochemical desorption of the
      molecular layer, resulting in the formation of endothelial cell-lined vascular
      like structures. In the following culture, the endothelial cells migrated into
      the collagen gel and formed branched luminal structures. However, this branching
      process was strikingly slow (>14 d) and the cell layers on the internal surfaces
      became disrupted in some regions. To address these issues, we examined the
      effects of the protein kinase C (PKC) activator, PMA, and shear stress generated
      by medium flow. Addition of PMA at an optimum concentration significantly
      accelerated migration, vascular network formation, and its stabilization.
      Exposure to shear stress reoriented the cells in the direction of the medium flow
      and further accelerated vascular network formation. Because of the synergistic
      effects, HUVECs began to sprout as early as 3 d of perfusion culture and
      neighboring vascular-like structures were bridged within 5 d. Although further
      investigations of vascular functions need to be performed, this approach may be
      an effective strategy for rapid fabrication of perfusable microvascular networks
      when engineering three-dimensional fully vascularized tissues and organs. 

PMID- 25860892
TI  - Diagnosis and management of Munchausen's Syndrome by Proxy.
AB  - A systematic literature review was conducted to identify and synthesise the
      relevant literature on the epidemiology, presentation, assessment and management
      of Munchausen's Syndrome by Proxy (MSP). This included collating information from
      published and unpublished sources. The purpose of the review was to provide an
      overview of the status of research into MSP. The results indicated that there are
      common areas of research and theorising on MSP. These areas were divided up into
      the following categories: definitions of MSP, diagnosis and recognition of MSP
      and management of MSP. The results of the literature review were summarised using
      the above-mentioned categories. The most widely accepted definitions of MSP
      included the International Classification of Diseases (10th edition) (ICD-10),
      (1994), Rosenberg (1987), The Diagnostic and Statistical Manual (4th edition)
      (1994) and Kelly and Loader (1997). The most common presentations of MSP
      identified included seizures, diarhhea, apnea and fevers. The most common forms
      of assault identified included suffocation, giving of drugs and poisoning. Mother
      perpetrator features, child-victim features and family features were identified
      as categories used to help with the identification of MSP. Appropriate management
      of MSP included careful consideration of child protection factors with the
      emphasis on comprehensive assessment and management. 

PMID- 25860891
TI  - De novo transcriptome assembly and the putative biosynthetic pathway of steroidal
      sapogenins of Dioscorea composita.
AB  - The plant Dioscorea composita has important applications in the medical and
      energy industries, and can be used for the extraction of steroidal sapogenins
      (important raw materials for the synthesis of steroidal drugs) and bioethanol
      production. However, little is known at the genetic level about how sapogenins
      are biosynthesized in this plant. Using Illumina deep sequencing, 62,341 unigenes
      were obtained by assembling its transcriptome, and 27,720 unigenes were
      annotated. Of these, 8,022 unigenes were mapped to 243 specific pathways, and 531
      unigenes were identified to be involved in 24 secondary metabolic pathways. 35
      enzymes, which were encoded by 79 unigenes, were related to the biosynthesis of
      steroidal sapogenins in this transcriptome database, covering almost all the
      nodes in the steroidal pathway. The results of real-time PCR experiments on ten
      related transcripts (HMGR, MK, SQLE, FPPS, DXS, CAS, HMED, CYP51, DHCR7, and
      DHCR24) indicated that sapogenins were mainly biosynthesized by the mevalonate
      pathway. The expression of these ten transcripts in the tuber and leaves was
      found to be much higher than in the stem. Also, expression in the shoots was low.
      The nucleotide and protein sequences and conserved domains of four related genes
      (HMGR, CAS, SQS, and SMT1) were highly conserved between D. composita and D.
      zingiberensis; but expression of these four genes is greater in D. composita.
      However, there is no expression of these key enzymes in potato and no steroidal
      sapogenins are synthesized. 

PMID- 25860893
TI  - A comparison between South African psychiatrists' and paediatricians' knowledge,
      attitudes and current practices regarding the management of children with
      Attention Deficit/Hyperactivity Disorder.
AB  - The objective of this study was to determine the knowledge, attitudes and current
      practices of psychiatrists and paediatricians in South Africa regarding the
      management of children with Attention Deficit/Hyperactivity Disorder (ADHD), to
      determine if there are significant differences between them. Three hundred and
      forty psychiatrists and 517 paediatricians were identified from the address list
      of the Health Professionals Council of South Africa. Each specialist was sent a
      survey questionnaire with a letter explaining the objectives and aims of the
      research. The questionnaire explored four themes: demographic data; attitudes to
      caring for children with ADHD; management of these children and knowledge about
      the use of stimulants. One hundred and seventy three (57.6%) psychiatrists and
      316 (61%) paediatricians responded. Of these 145 and 278 respectively were
      practising medicine, and 51.7% (75) of the psychiatrists and 61% (169) of the
      paediatricians indicated that they manage children with ADHD. The results of the
      survey indicate that paediatricians and psychiatrists have adequate knowledge of
      ADHD and its management. Possibly because of the organisation of their practices
      psychiatrists were not as concerned as paediatricians about the time spent on
      each patient, but they were less likely to refer to other professionals. On the
      other hand, paediatricians had more of an interdisciplinary approach to the
      management of children with ADHD, but found them time consuming, remuneration
      inadequate and had little time to prepare extensive reports or liase with other
      professionals or schools. Psychiatrists appear to function within a neuro
      biological model and have more knowledge on neuro-pharmacology and physiology.
      Paediatricians have a greater educational and family awareness, possibly
      reflecting differences in training. Both groups use methylphenidate as the
      medication of choice and both have adequate knowledge of its benefits, side
      effects and contra-indications. 

PMID- 25860894
TI  - Stress, psychological symptoms, social support and health behaviour among black
      students in South Africa.
AB  - The study investigated stress events, perceived stress and social support in
      relation to various common health behaviours among black South African students.
      The sample included 624 students: 314 Grade 12 Secondary school students and 310
      third year social science university students in South Africa. The study found a
      low prevalence of healthy behaviour, which was inversely related to psychological
      symptoms and depressive symptoms and positively related to social support and
      perceived stress. It is suggested that psychological symptoms and social support
      need to be included in enhancing lifestyle intervention programmes among youth. 

PMID- 25860895
TI  - Children and adolescents' exposure to traumatic war stressors in the Democratic
      Republic of Congo.
AB  - This study focuses on post-traumatic reactions of children and adolescents in the
      Democratic Republic of Congo. The study was conducted in Butembo between April
      2001 and May 2001 during the ongoing war that started on 2 August 1999. Semi
      structured interviews combining a mix of open- and closed-ended questions were
      used to collect data from 88 children (44 girls and 44 boys) and 91
      schoolteachers (40 women and 51 men) in 24 elementary and 20 secondary schools.
      The results show that both children and adolescents, and schoolteachers, are
      traumatised by war-related traumatic events such as shooting, loss of family
      members and forced recruitment into the armed forces. For example, 72.59%
      children and adolescents said they had lost a family member, 95.45% had
      experienced shooting, and 75% reported high levels of insecurity leading to a
      decline in school performance. The research suggests that international agencies
      devoted to protecting young people should provide assistance even during war,
      because the cost of healing may be too high if action is only taken later.
      Special attention should be given to teachers, arming them with skills that will
      equip them in supporting traumatised children. 

PMID- 25860896
TI  - Measuring adolescents' exposure to violence and related PTSD symptoms:
      Reliability of an adaptation of the Harvard Trauma Questionnaire.
AB  - Objective - This study aimed to assess the reliability of an adaptation of the
      Harvard Trauma Questionnaire for use in epidemiological investigations of
      adolescents' exposure to violence and related post-traumatic stress disorder
      (PTSD) symptoms. Method - The exposure items of the Harvard Trauma Questionnaire
      were adapted for the South African context. The symptoms scale was left intact.
      Self-report questionnaires were administered on two occasions to 104 students in
      four high schools in Cape Town, South Africa. Test-retest reliability was
      assessed using Cohen's kappa (k) and observed agreement, as well as a concordance
      correlation coefficient for the symptoms scale. Cronbach's alpha was used to
      assess internal consistency of the symptoms scale. Results - All but one item
      showed at least fair test-retest reliability. Cronbach's alpha for the symptoms
      scale was 0.92, and the concordance correlation coefficient between the total
      symptoms score at time 1 and time 2 was 0.64 (95% CI = 0.51-0.74). Conclusions -
      Results suggest that the instrument may be sufficiently reliable for use in
      epidemiological studies of adolescent populations, although this sample is
      limited in several key respects. Further studies should investigate reliability
      in broader samples, as well as examining validity. 

PMID- 25860897
TI  - The Mifne Method - ISRAEL. Early intervention in the treatment of autism/PDD: A
      therapeutic programme for the nuclear family and their child.
AB  - The paper will present the Mifne (turning point) Method for early intervention in
      the treatment of the Autism spectrum, which has been developed as an intensive,
      short-term therapy programme for infants: the youngest infant treated at the
      Center was five months old. The Mifne approach is derived from attachment theory.
      The programme is designed to treat families with children under the age of five.
      The sequential programme includes three stages: 1. Intensive system therapy for
      the nuclear family that continues for a three week period in residence at the
      Center. 2. Follow-up treatment takes place at the family home. 3. Integration of
      the child into mainstream education. A retrospective evaluation of the programme
      undertaken by the Schneider Children's Medical Center revealed that children
      showed improvement on almost all items of two scales: the Childhood Autism Rating
      Scale (CARS) and the Social Behavior Rating Scale (SBRS). Total scores on both
      scales showed significant improvement after three weeks and after six months.
      Follow-up data shows that 73% of the children treated at the Center have been
      integrated in mainstream schools. Clearly, early detection and treatment in the
      first year of life can redirect the infant's development and might avoid the
      escalation of autistic symptoms. An illustrative case study is described. 

PMID- 25860898
TI  - Adoption, fostering and identity.
AB  - The authors propose to look at how identity is formed in young adopted or foster
      children. On the basis that the identity results from a relational process, two
      criteria will be considered as key elements for the individual's sense of self:
      the necessity of belonging and the need for differentiation. In the case of
      adopted/foster children, this process acquires particular characteristics. The
      condition of non-biological filiation not only requires parents and children to
      employ different methods and time-frames as they construct a bond of secure
      attachment, but also asks parents to have a greater awareness of relationship. As
      an internal model for the psyche, the modulation between belonging and
      differentiation will shape the child's identity. It presents itself to both
      adoptive and foster children and parents as a particularly delicate journey in
      relationships that often needs professional help so as to avoid another failed
      relationship. 

PMID- 25860899
TI  - Some thoughts about the impact of domestic violence on infants and young
      children.
AB  - This paper describes the impact on children of both the primary trauma of severe
      domestic violence and the secondary consequences of chronic situations where
      domestic violence forms part of a general background of neglect, deprivation and
      abuse. Links are made with Main's (1995) description of 'Disorganised' Attachment
      behaviour in children who are faced with a frightening or frightened parent. The
      paper stresses the importance of good early experiences within the family and how
      domestic violence can interfere with the basic requirements for the physical and
      emotional survival of the infant. Clinical vignettes illustrate these ideas. 

PMID- 25860900
TI  - Beyond feeders and growers: Changing conceptions of care in the Western Cape.
AB  - This paper summarises reciprocal learning between the author and South African
      colleagues and caregivers during a curriculum development project for birth-to
      three caregivers in peri-urban settlements in the Western Cape. The curriculum
      was conceived as a self-conscious blending of Western scientific ideas of early
      development with African values and patterns of care, emphasising the importance
      of early emotional development. Over a three-year-period the course was refined
      through pilot trainings and is now available through Grassroots Educare Trust, to
      be used countrywide. The shared learning from all parties involved speaks to the
      need for greater resources to be provided and for more attention be paid to the
      learning and wellbeing of informal caregivers. It also points to the need for
      increased collaboration between the rather separate worlds of early
      care/education and infant mental health. 

PMID- 25860901
TI  - Social aggression among girls by marion k underwood.

PMID- 25860902
TI  - Psychoanalytic approaches to the treatment of children and adolescents: tradition
      and transformation by jerrold R brandell.

PMID- 25860904
TI  - Child development: thinking about theories by phillip slee and rosalyn shute.

PMID- 25860903
TI  - Mood and Anxiety Disorders in Children and Adolescents. A psychophar- macological
      approach by D Nutt, C Bell, C Masterson and C Short.

PMID- 25860905
TI  - Mental health impacts of HIV/AIDS on children.

PMID- 25860906
TI  - Criminal law (sexual offences) amendment bill.

PMID- 25860734
TI  - Search for Higgs and Z Boson Decays to J/psigamma and Upsilon(nS)gamma with the
      ATLAS Detector.
AB  - A search for the decays of the Higgs and Z bosons to J/psigamma and
      Upsilon(nS)gamma (n=1,2,3) is performed with pp collision data samples
      corresponding to integrated luminosities of up to 20.3  fb^{-1} collected at
      sqrt[s]=8  TeV with the ATLAS detector at the CERN Large Hadron Collider. No
      significant excess of events is observed above expected backgrounds and 95% C.L.
      upper limits are placed on the branching fractions. In the J/psigamma final state
      the limits are 1.5*10^{-3} and 2.6*10^{-6} for the Higgs and Z boson decays,
      respectively, while in the Upsilon(1S,2S,3S)gamma final states the limits are
      (1.3,1.9,1.3)*10^{-3} and (3.4,6.5,5.4)*10^{-6}, respectively. 

PMID- 25860907
TI  - Immunohistochemical Evaluation of Leptin Role in Skin Tags.
AB  - Skin tags (STs) are common benign dermal connective tissue neoplasms that are
      mainly composed of loose fibrous tissue. However, their exact etiology is not
      fully understood. Leptin is a major player in the biology and pathology of the
      skin and its appendages. It is linked to cell differentiation, proliferation,
      migration, and survival with pronounced effects on angiogenesis, blood flow, and
      tissue perfusion. This study aimed at investigating the possible role of leptin
      in STs pathogenesis and correlating its expression with different clinical and
      histopathological parameters. Using immunohistochemical techniques, we examined
      90 subjects. These included 60 non-obese cases with STs and 30 age-, gender- and
      Body Mass Index-matched normal subjects as a control group. Leptin was
      overexpressed in STs compared with normal skin (p < .001). Nuclear and
      nucleocytoplasmic patterns were significantly associated with cases both in
      epidermis (p < .04) and dermis (p < .001). Higher epidermal leptin H score was
      significantly associated with female gender (p = .004) and haphazard collagen
      arrangement (p < .03). Higher dermal leptin H score was significantly associated
      with smooth skin tags (p = .01), dilated blood vessels (p = .04), presence of
      mast cells (MCs) (p = .002), presence of inflammatory cells (p = .004), and
      haphazard collagen arrangement (p < .001). In conclusion, leptin may play a role
      in STs pathogenesis through its effects on keratinocytes, fibroblasts and
      vascular endothelium. Further studies are recommended to clarify the molecular
      interplay between leptin and MCs in ST pathogenesis. Further studies are also
      needed to determine the significance of its nuclear expression. 

PMID- 25860908
TI  - Surface characterization and in vivo evaluation of dual Acid-etched and grit
      blasted/acid-etched implants in sheep.
AB  - PURPOSE: Dual acid-etching is widely used to modify dental implant topography and
      enhance early bone healing. This study evaluated the histomorphometric,
      biomechanical, and histological bone response to acid-etched (AA) in comparison
      with grit-blasted/acid-etched (GB) and machined control (C) implants within sites
      of relatively low-bone remodeling rates. MATERIALS AND METHODS: Implant surface
      topography was evaluated by scanning electron microscopy and optical
      interferometry (IFM). Six adult male sheep (n = 6) received 72 Ti-6Al-4V implants
      (n = 24 per surface) in both ilium (n = 12 per bone bilaterally). The implants
      remained for 3 and 6 weeks in vivo. The histomorphometric parameters bone-implant
      contact (BIC) and bone area fraction occupancy (BAFO) were evaluated.
      Biomechanical analysis consisted of torque-to-interface failure. RESULTS: IFM
      analysis showed the highest average surface roughness for GB and the highest
      density of summits and developed surface area percentage (P < 0.01) for AA. No
      difference was observed in BAFO for all groups in 3 and 6 weeks. Increased BIC
      and torque resistance were observed for AA implants at both time points after
      implantation. CONCLUSIONS: Overall, improved bone-to-implant response was
      observed for the AA implant surface.

PMID- 25860912
TI  - Correction: JNK controls the onset of mitosis in planarian stem cells and
      triggers apoptotic cell death required for regeneration and remodeling.

PMID- 25860909
TI  - Skills of general health workers in primary eye care in Kenya, Malawi and
      Tanzania.
AB  - BACKGROUND: Primary eye care (PEC) in sub-Saharan Africa usually means the
      diagnosis, treatment, and referral of eye conditions at the most basic level of
      the health system by primary health care workers (PHCWs), who receive minimal
      training in eye care as part of their curricula. We undertook this study with the
      aim to evaluate basic PEC knowledge and ophthalmologic skills of PHCWs, as well
      as the factors associated with these in selected districts in Kenya, Malawi, and
      Tanzania. METHODS: A standardized (26 items) questionnaire was administered to
      PHCWs in all primary health care (PHC) facilities of 2 districts in each country.
      Demographic information was collected and an examination aimed to measure
      competency in 5 key areas (recognition and management of advanced cataract,
      conjunctivitis, presbyopia, and severe trauma plus demonstrated ability to
      measure visual acuity) was administered. RESULTS: Three-hundred-forty-three PHCWs
      were enrolled (100, 107, and 136 in Tanzania, Kenya, and Malawi, respectively).
      The competency scores of PHCW varied by area, with 55.7%, 61.2%, 31.2%, and 66.1%
      scoring at the competency level in advanced cataract, conjunctivitis, presbyopia,
      and trauma, respectively. Only 8.2% could measure visual acuity. Combining all
      scores, only 9 (2.6%) demonstrated competence in all areas. CONCLUSION: The
      current skills of health workers in PEC are low, with a large per cent below the
      basic competency level. There is an urgent need to reconsider the expectations of
      PEC and the content of training.

PMID- 25860913
TI  - The effects of a smoking cessation programme on health-promoting lifestyles and
      smoking cessation in smokers who had undergone percutaneous coronary
      intervention.
AB  - Smoking is a major risk factor for not only the occurrence of myocardial
      ischaemia but also recurrences of vascular stenosis. This study aimed to evaluate
      health-promoting lifestyles and abstinence rate after a smoking cessation
      programme. Sixty-two smokers who had undergone percutaneous coronary intervention
      were randomly assigned to either the experimental or control group. The
      experimental group (n = 30) received 10 phone counselling sessions and 21 short
      message service messages for abstinence and coronary disease prevention, whereas
      the control group (n = 32) received only the standard education. After the
      intervention, 14 members of the experimental group had switched to a non-smoking
      status, confirmed biochemically; moreover, their physical activity and stress
      management scores increased significantly. However, self-efficacy of smoking
      cessation was not reflected in the cotinine levels. Thus, it is necessary not
      only to increase self-efficacy but also to determine the factors that affect the
      success of smoking cessation so that they can be included in the intervention.
      Our results suggest that phone counselling and short message service messaging
      might be important tools for the realization of smoking cessation and lifestyle
      changes among patients who have undergone percutaneous coronary intervention. 

PMID- 25860914
TI  - Linguistic Feature Development Across Grades and Genre in Elementary Writing.
AB  - PURPOSE: As children develop skills in writing across academic contexts,
      clinicians and educators need to have a fundamental understanding of typical
      writing development as well as valid and reliable assessment methods. The purpose
      of this study was to examine the progression of linguistic elements in school-age
      children's narrative and expository writing development. METHOD: Narrative and
      expository writing samples produced by 89 children in Grades 2 through 4 were
      analyzed at the microstructure and macrostructure levels. Measures of receptive
      vocabulary, word-level reading, and reading comprehension were obtained. RESULTS:
      Exploratory factor analyses revealed 4 microstructure factors (e.g.,
      productivity, grammatical complexity, grammatical accuracy, and lexical density)
      and 1 macrostructure factor (e.g., a combination of organization, text structure,
      and cohesion). Multivariate analyses of covariance with reading comprehension as
      a covariate showed that productivity and macrostructure were sensitive to grade
      level and genre differences and that expository grammatical complexity was
      sensitive to grade-level differences. CONCLUSIONS: Findings are discussed in
      light of grade-level standards for narrative and expository writing and current
      practices in writing assessment. Multiple suggestions are offered for clinical
      and educational implications, and specific directions are provided for future
      research.

PMID- 25860910
TI  - Tailor-made ezrin actin binding domain to probe its interaction with actin in
      vitro.
AB  - Ezrin, a member of the ERM (Ezrin/Radixin/Moesin) protein family, is an Actin
      plasma membrane linker protein mediating cellular integrity and function. In-vivo
      study of such interactions is a complex task due to the presence of a large
      number of endogenous binding partners for both Ezrin and Actin. Further, C
      terminal actin binding capacity of the full length Ezrin is naturally shielded by
      its N-terminal, and only rendered active in the presence of Phosphatidylinositol
      bisphosphate (PIP2) or phosphorylation at the C-terminal threonine. Here, we
      demonstrate a strategy for the design, expression and purification of constructs,
      combining the Ezrin C-terminal actin binding domain, with functional elements
      such as fusion tags and fluorescence tags to facilitate purification and
      fluorescence microscopy based studies. For the first time, internal His tag was
      employed for purification of Ezrin actin binding domain based on in-silico
      modeling. The functionality (Ezrin-actin interaction) of these constructs was
      successfully demonstrated by using Total Internal Reflection Fluorescence
      Microscopy. This design can be extended to other members of the ERM family as
      well. 

PMID- 25860915
TI  - LRIG1 inhibits hypoxia-induced vasculogenic mimicry formation via suppression of
      the EGFR/PI3K/AKT pathway and epithelial-to-mesenchymal transition in human
      glioma SHG-44 cells.
AB  - Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) is a pan-negative
      regulator of the epidermal growth factor receptor (EGFR) signaling pathway. The
      aim of this study was to investigate the underlying mechanism of LRIG1 in the
      regulation of vasculogenic mimicry (VM) formation in glioma cells. We constructed
      an enhanced green fluorescent protein plasmid (pEGFP) system, pEGFP-C1-LRIG1, for
      overexpression of LRIG1, and transfected it into human glioma cell line SHG-44.
      Under hypoxic conditions induced by CoCl2, we investigated the effects of LRIG1
      overexpression on VM formation and VM-dependent malignant behaviors including
      migration, invasion, and proliferation. Additionally, we explored the effects of
      LRIG1 on the expression levels of major components of the EGFR/PI3K/AKT pathway
      as well as E-cadherin and vimentin. We found that LRIG1 overexpression is able to
      inhibit hypoxia-induced VM formation, migration, invasion, and proliferation.
      Furthermore, LRIG1 overexpression counteracts hypoxia-induced increase in the
      expression of phosphorylated EGFR (pEGFR), PI3K (pPI3K), and AKT (pAKT) and
      reverts hypoxia-induced alteration in E-cadherin and vimentin expression levels.
      In LRIG1 knockdown SHG-44 cells, however, hypoxia-induced VM formation and
      alteration in E-cadherin and vimentin expression levels were exacerbated. These
      results suggest that the inhibitory effects of LRIG1 are most likely mediated by
      suppression of the EGFR/PI3K/AKT pathway and epithelial-mesenchymal transition
      (EMT) process. Our findings provide compelling evidence implicating LRIG1 in
      glioma pathophysiology, suggesting that gene therapy using LRIG1 may serve as a
      treatment for this disease. 

PMID- 25860911
TI  - Long term effect of curcumin in restoration of tumour suppressor p53 and phase-II
      antioxidant enzymes via activation of Nrf2 signalling and modulation of
      inflammation in prevention of cancer.
AB  - Inhibition of carcinogenesis may be a consequence of attenuation of oxidative
      stress via activation of antioxidant defence system, restoration and
      stabilization of tumour suppressor proteins along with modulation of inflammatory
      mediators. Previously we have delineated significant role of curcumin during its
      long term effect in regulation of glycolytic pathway and angiogenesis, which in
      turn results in prevention of cancer via modulation of stress activated genes.
      Present study was designed to investigate long term effect of curcumin in
      regulation of Nrf2 mediated phase-II antioxidant enzymes, tumour suppressor p53
      and inflammation under oxidative tumour microenvironment in liver of T-cell
      lymphoma bearing mice. Inhibition of Nrf2 signalling observed during lymphoma
      progression, resulted in down regulation of phase II antioxidant enzymes, p53 as
      well as activation of inflammatory signals. Curcumin potentiated significant
      increase in Nrf2 activation. It restored activity of phase-II antioxidant enzymes
      like GST, GR, NQO1, and tumour suppressor p53 level. In addition, curcumin
      modulated inflammation via upregulation of TGF-beta and reciprocal regulation of
      iNOS and COX2. The study suggests that during long term effect, curcumin leads to
      prevention of cancer by inducing phase-II antioxidant enzymes via activation of
      Nrf2 signalling, restoration of tumour suppressor p53 and modulation of
      inflammatory mediators like iNOS and COX2 in liver of lymphoma bearing mice. 

PMID- 25860917
TI  - Outcome-changing effect of polarity reversal in hydrogen-atom-abstraction
      reactions.
AB  - We have examined hydrogen-atom-abstraction reactions for combinations of
      electrophilic/nucleophilic radicals with electrophilic/nucleophilic substrates.
      We find that reaction between an electrophilic radical and a nucleophilic
      substrate is relatively favorable, and vice versa, but the reactions between a
      radical and a substrate that are both electrophilic or both nucleophilic are
      relatively unfavorable, consistent with the literature reports of Roberts. As a
      result, the regioselectivity for the abstraction from a polar substrate can be
      reversed by reversing the polarity of the attacking radical. Our calculations
      support Roberts' polarity-reversal-catalysis concept and suggest that addition of
      a catalyst of appropriate electrophilicity/nucleophilicity can lead to an
      enhancement of the reaction rate of approximately 5 orders of magnitude. By
      exploiting the control over regioselectivity associated with the polar nature of
      the radical and the substrate, we demonstrate the possibility of directing the
      regioselectivity of hydrogen abstraction from amino acid derivatives and
      simultaneously providing a significant rate acceleration. 

PMID- 25860916
TI  - Mesenchymal stem cell-based HSP70 promoter-driven VEGFA induction by resveratrol
      promotes angiogenesis in a mouse model.
AB  - Several studies of stem cell-based gene therapy have indicated that long-lasting
      regeneration following vessel ischemia may be stimulated through VEGFA gene
      therapy and/or MSC transplantation for reduction of ischemic injury in limb
      ischemia and heart failure. The therapeutic potential of MSC transplantation can
      be further improved by genetically modifying MSCs with genes which enhance
      angiogenesis following ischemic injury. In the present study, we aimed to develop
      an approach in MSC-based therapy for repair and mitigation of ischemic injury and
      regeneration of damaged tissues in ischemic disease. HSP70 promoter-driven VEGFA
      expression was induced by resveratrol (RSV) in MSCs, and in combination with
      known RSV biological functions, the protective effects of our approach were
      investigated by using ex vivo aortic ring coculture system and a 3D scaffolds in
      vivo model. Results of this investigation demonstrated that HSP promoter-driven
      VEGFA expression in MSC increased approximately 2-fold over the background VEGFA
      levels upon HSP70 promoter induction by RSV. Exposure of HUVEC cells to medium
      containing MSC in which VEGFA had been induced by cis-RSV enhanced tube formation
      in the treated HUVEC cells. RSV-treated MSC cells differentiated into endothelial
      like phenotypes, exhibiting markedly elevated expression of endothelial cell
      markers. These MSCs also induced aortic ring sprouting, characteristic of
      neovascular formation from pre-existing vessels, and additionally promoted
      neovascularization at the MSC transplantation site in a mouse model. These
      observations support a hypothesis that VEGFA expression induced by cis-RSV acting
      on the HSP70 promoter in transplanted MSC augments the angiogenic effects of stem
      cell gene therapy. The use of an inducible system also vastly reduces possible
      clinical risks associated with constitutive VEGFA expression. 

PMID- 25860918
TI  - Classification of foodborne pathogens using near infrared (NIR) laser scatter
      imaging system with multivariate calibration.
AB  - An optical sensor system, namely NIR laser scatter imaging system, was developed
      for rapid and noninvasive classification of foodborne pathogens. This developed
      system was used for images acquisition. The current study is focused on exploring
      the potential of this system combined with multivariate calibrations in
      classifying three categories of popular bacteria. Initially, normalization and
      Zernike moments extraction were performed, and the resultant translation, scale
      and rotation invariances were applied as the characteristic variables for
      subsequent discriminant analysis. Both linear (LDA, KNN and PLSDA) and nonlinear
      (BPANN, SVM and OSELM) pattern recognition methods were employed comparatively
      for modeling, and optimized by cross validation. Experimental results showed that
      the performances of nonlinear tools were superior to those of linear tools,
      especially for OSELM model with 95% discrimination rate in the prediction set.
      The overall results showed that it is extremely feasible for rapid and
      noninvasive classifying foodborne pathogens using this developed system combined
      with appropriate multivariate calibration. 

PMID- 25860919
TI  - Does sustained involvement in a quality network lead to improved performance?
AB  - PURPOSE: The purpose of this paper is to explore the effects of prolonged
      investment in one quality improvement method, which are uncertain. The authors
      aim to examine the extent to which sustained involvement in a quality network
      over five years led to improved performance against standards, and whether
      improvement was achieved in areas where service staff could exercise direct
      control. DESIGN/METHODOLOGY/APPROACH: A prospective cohort design was used to
      examine data from 48 UK inpatient child and adolescent mental health units
      between 2005/2006 and 2009/2010, which had been Quality Network for In-patient
      CAMHS members for two years. These were selected to remove the initial marked
      increase in compliance identified in an earlier study. The main outcome measure
      was compliance with organisation process standards. FINDINGS: Units meeting
      "excellent" quality status across all standards rose from seven (14.6 per cent)
      to 18 (37.5 per cent). Standards for Environment and Facilities and Access,
      Admission and Discharge improved the most. Units meeting the "excellent" quality
      status for criteria over which staff had direct control criteria rose from 17
      (35.4 per cent) to 29 (60.4 per cent) over the five-year period. The unit modal
      quality status categorisation for criteria where staff had no direct control in
      2005/2006 was "poor" (n=25; 52.1 per cent) but had progressed to "good" in
      2009/2010 (n=24; 50.0 per cent). ORIGINALITY/VALUE: The authors provide evidence
      that sustained investment in one QI method raises service compliance against
      standards. Trends showed improvement for direct control standards from "good" to
      "excellent" levels and improvement for no direct control from "poor" to "good".

PMID- 25860921
TI  - National early warning score (NEWS) - evaluation in surgery.
AB  - PURPOSE: The purpose of this paper is to evaluate staff opinion on the impact of
      the National Early Warning Score (NEWS) system on surgical wards. In 2012, the
      NEWS system was introduced to Irish hospitals on a phased basis as part of a
      national clinical programme in acute care. DESIGN/METHODOLOGY/APPROACH: A
      modified established questionnaire was given to surgical nursing staff, surgical
      registrars, surgical senior house officers and surgical interns for completion
      six months following the introduction of the NEWS system into an Irish university
      hospital. FINDINGS: Amongst the registrars, 89 per cent were unsure if the NEWS
      system would improve patient care. Less than half of staff felt consultants and
      surgical registrars supported the NEWS system. Staff felt the NEWS did not
      correlate well clinically with patients within the first 24 hours (Day zero) post
      operatively. Furthermore, 78-85 per cent of nurses and registrars felt a rapid
      response team should be part of the escalation protocol. RESEARCH
      LIMITATIONS/IMPLICATIONS: Senior medical staff were not convinced that the NEWS
      system may improve patient care. Appropriate audit proving a beneficial impact of
      the NEWS system on patient outcome may be essential in gaining support from
      senior doctors. Deficiencies with the system were also observed including the
      absence of a rapid response team as part of the escalation protocol and a lack of
      concordance of the NEWS in patients Day zero post-operatively. These issues
      should be addressed moving forward. ORIGINALITY/VALUE: Appropriate audit of the
      impact of the NEWS system on patient outcome may be pertinent to obtain the
      support from senior doctors. Deficiencies with the system were also observed
      including the absence of a rapid response team as part of the escalation protocol
      and a lack of concordance of the NEWS in patients Day zero post-operatively.
      These issues should be addressed moving forward.

PMID- 25860920
TI  - TeamSTEPPS implementation in community hospitals: adherence to recommended
      training approaches.
AB  - PURPOSE: Team Strategies and Tools to Enhance Performance and Patient Safety
      (TeamSTEPPS) is being widely promoted in healthcare settings to train staff in
      evidence-based approaches that promote patient safety. It involves a
      comprehensive curriculum that spells out key principles and actionable tools for
      a culture change toward patient-safety-focussed teamwork. Activities begin with
      selected personnel attending TeamSTEPPS Master Trainer Training (MTT) and then
      organizing and providing TeamSTEPPS training for staff in their organization. The
      authors conducted interviews with respondents at community hospitals conducting
      TeamSTEPPS staff training. To structure the interviews, the authors used 11 key
      questions identified by Weaver et al. in their in-depth team training literature
      review. The purpose of this paper is to examine approaches taken by community
      hospital personnel and compare those to the best practices recommended by Weaver
      et al. DESIGN/METHODOLOGY/APPROACH: The authors interviewed 57 staff and
      administrators at 22 community hospitals sending teams to TeamSTEPPS MTT.
      FINDINGS: The authors find that training implementation in community hospitals
      differs significantly from the established, research-based principles for
      effective team training described in the research literature, which is largely
      based in academic medical centers. ORIGINALITY/VALUE: The current findings
      suggest that several TeamSTEPPS training features could be enhanced in community
      hospitals including: choosing staff who have the skills to be effective trainers
      in this train-the-trainer model; emphasizing active learning; and sustaining
      lessons through on-the-job application, practice and feedback. These principles
      apply to many training approaches employed in small healthcare organizations.

PMID- 25860922
TI  - The trust-commitment challenge in service quality-loyalty relationships.
AB  - PURPOSE: The purpose of this paper is to develop and empirically test a model to
      examine service quality, satisfaction, trust and commitment as loyalty
      antecedents in a private healthcare service. DESIGN/METHODOLOGY/APPROACH: The
      approach was tested using structural equation modelling, involving 175 patients
      from a private Portuguese healthcare unit, using a revised Service Quality
      Assessment Scale (SQAS) scale for service quality evaluation. FINDINGS: The scale
      used to evaluate service quality is valid and meaningful. Service quality proved
      to be a multidimensional construct and relevant to build satisfaction. The path
      satisfaction->trust->loyalty was validated, whereas the path satisfaction
      >commitment->loyalty was not statistically supported. RESEARCH
      LIMITATIONS/IMPLICATIONS: The revised SQAS scale showed good internal consistency
      in healthcare context. Further trust-commitment antecedents must be examined in a
      private healthcare landscape to generalise the findings. PRACTICAL IMPLICATIONS:
      Healthcare quality managers must explore the service quality dimensions to
      generate satisfaction among their patients. Developing trust generates positive
      patient attitudes and loyalty. ORIGINALITY/VALUE: This study explores using the
      SQAS scale in a private healthcare context. The authors provide further evidence
      that service quality is an antecedent and different from satisfaction. All the
      measures used proved to be valid and reliable. Trust and commitment play
      different roles in their relationship with loyalty.

PMID- 25860923
TI  - Medical laboratory quality systems - a management review.
AB  - PURPOSE: The purpose of this paper is to highlight changes in ISO 15189:2012 and
      ISO 15189:2007 concerning management review requirements and to present a
      management review checklist, which includes all the revised ISO 15189's
      requirements. DESIGN/METHODOLOGY/APPROACH: The recent revised and updated ISO
      15189:2012 standard recommends a management review using a process approach and
      includes some additional topics. FINDINGS: The management review is a key element
      in many quality management systems, including medical laboratory management
      systems in accordance with ISO 15189. The process approach enables laboratory top
      managers and personnel to achieve all the quality management system's important
      inputs and outputs. ORIGINALITY/VALUE: As laboratory staff often encounter
      difficulties fully exploiting the management review process, this checklist helps
      laboratory staff carry out an effective management review covering all the
      quality management system's important aspects.

PMID- 25860924
TI  - Can patients detect hazardous dental practice? A patient complaint study.
AB  - PURPOSE: The purpose of this paper is to: determine the prevalence and
      distribution of patient/family-generated, dentistry-related complaints to
      Regional State Administrative Agencies (AVIs) and the National Supervisory
      Authority for Welfare and Health (Valvira) in Finland from 2000 to 2011, study
      patient/family safety incident experiences and other reasons for complaints,
      assess complaint validity and evaluate factors associated with disciplinary
      processes against dentists. DESIGN/METHODOLOGY/APPROACH: Data included closed
      cases handled by AVIs and Valvira (2000-2011) against dental practitioners or
      dental practice units (n=782). The authors analysed the complaints distribution
      and examined the antecedent factors and circumstances. FINDINGS: This study
      demonstrated that patients/families can detect many dental treatment hazards,
      substandard processes and even serious safety risks rather well. The
      investigation processes revealed some physical harm or potential patient safety
      (PS) risks in more than half the alleged cases. Many complaints accumulated
      against certain individuals and statistically significant positive correlations
      were found between some patient/family complaints, dentist-specific variables and
      disciplinary actions. PRACTICAL IMPLICATIONS: Patient/family-generated complaints
      must be taken seriously and seen as relatively good safety risk indicators.
      However, more knowledge on how patients might cooperate with dental care
      providers to prevent errors is needed. ORIGINALITY/VALUE: This work provides a
      unique opportunity to learn from several dentistry-related patient complaints.
      Despite some limitations, patient complaints appear to be useful as a
      complementary source together with other PS study methods.

PMID- 25860925
TI  - Human factors paradigm and customer care perceptions.
AB  - PURPOSE: The purpose of this paper is to examine if customer care (CC) can be
      directly linked to patient safety through a human factors (HF) framework.
      DESIGN/METHODOLOGY/APPROACH: Data from an online questionnaire, completed by a
      convenience healthcare worker sample (n=373), was interrogated using thematic
      analysis within Vincent et al.'s (1998) HF theoretical framework. This proposes
      seven areas affecting patient safety: institutional context, organisation and
      management, work environment, team factors, individual, task and patient.
      FINDINGS: Analysis identified responses addressing all framework areas. Responses
      (597) principally focused on work environment 40.7 per cent (n=243), organisation
      and management 28.8 per cent (n=172). Nevertheless, reference to other framework
      areas were clearly visible within the data: teams 10.2 per cent (n=61),
      individual 6.7 per cent (n=40), patients 6.0 per cent (n=36), tasks 4.2 per cent
      (n=24) and institution 3.5 per cent (n=21). Findings demonstrate congruence
      between CC perceptions and patient safety within a HF framework. RESEARCH
      LIMITATIONS/IMPLICATIONS: The questionnaire requested participants to identify
      barriers to rather than CC enablers. Although this was at a single site complex
      organisation, it was similar to those throughout the NHS and other international
      health systems. PRACTICAL IMPLICATIONS: CC can be viewed as consonant with
      patient safety rather than the potentially dangerous consumerisation stance,
      which could ultimately compromise patient safety. ORIGINALITY/VALUE: This work
      provides an original perspective on the link between CC and patient safety and
      has the potential to re-focus healthcare perceptions.

PMID- 25860926
TI  - Perceived service quality's effect on patient satisfaction and behavioural
      compliance.
AB  - PURPOSE: The purpose of this paper is to advance healthcare service quality
      research using hierarchical component models. DESIGN/METHODOLOGY/APPROACH: This
      study used a quantitative approach with cross-sectional design as a survey
      method, combining cluster and convenience sampling and partial least square
      structural equation modelling (PLS-SEM) to validate the research model and test
      the hypotheses. FINDINGS: The study extends health service quality literature by
      showing that: patient satisfaction (PS) is dominant, significant and indirect
      determinant of behavioural compliance (BC); perceived service quality has the
      strongest effect on BC via PS. RESEARCH LIMITATIONS/IMPLICATIONS: Only one
      hospital was evaluated. PRACTICAL IMPLICATIONS: The study provides managers with
      a service quality model for conducting integrated service delivery systems
      analysis and design. ORIGINALITY/VALUE: Overall, the study makes a significant
      contribution to healthcare organizations, better health outcomes for patients and
      better quality of life for the community.

PMID- 25860927
TI  - Split anergized Natural Killer cells halt inflammation by inducing stem cell
      differentiation, resistance to NK cell cytotoxicity and prevention of cytokine
      and chemokine secretion.
AB  - The mechanism of suppression of NK cytotoxicity in cancer patients is not clearly
      established. In this paper we provide evidence that anergized NK cells induce
      differentiation of healthy Dental Pulp Stem Cells (DPSCs) or transformed Oral
      Squamous Cancer Stem Cells (OSCSCs) resulting in cell growth inhibition,
      resistance to NK cell-mediated cytotoxicity and prevention of inflammatory
      mediators secretion. Induction of cytotoxicity resistance in differentiated cells
      correlated with increased CD54 and MHC class I surface expression and mediated by
      the combination of IFN-gamma and TNF-alpha since antibodies to both, but not each
      cytokine alone, was able to inhibit resistance. In contrast, inhibition of
      cytokine and chemokine release was mediated by IFN-gamma since the addition of
      anti-IFN-gamma antibody, and not anti-TNF-alpha, restored secretion of
      inflammatory mediators in NK cell cultures with differentiated DPSCs and OSCSCs.
      There was a gradual and time dependent decrease in MHC class I and CD54
      expression which correlated with the restoration of NK cell cytotoxicity,
      augmentation of cytokine secretion and increased cell growth from days 0-12 post
      NK removal. Continuous presence of NK cells is required for the maintenance of
      cell differentiation since the removal of NK cell-mediated function reverses the
      phenotype and function of differentiated cells to their stem-like cells. 

PMID- 25860928
TI  - Recurrence of glioblastoma after radio-chemotherapy is associated with an
      angiogenic switch to the CXCL12-CXCR4 pathway.
AB  - Angiogenesis is one of the key features of glioblastoma (GBM). Our objective was
      to explore the potential changes of angiogenic factors in GBM between initial
      diagnosis and recurrence after radiotherapy-temozolomide (RT/TMZ). Paired frozen
      tumors from both initial and recurrent surgery were available for 29 patients.
      Screening of genes expressions related to angiogenesis was performed using RT-
      PCR arrays on 10 first patients. Next, RNA expressions of the selected genes were
      analyzed on all samples. Protein expression was examined by immunohistochemistry.
      The anti-tumor effect of AMD3100 (anti-CXCR4) was tested in GBM explants. In the
      screening step, the initial-recurrence expression changes contributed to a
      selection of seven genes (VEGFA, VEGFR2, VEGFR1, CXCL12, CXCR4, uPA HIF1alpha).
      By quantitative RT-PCR, RNA expressions of CXCR4 (p = 0.029) and CXCL12 (p =
      0.107) were increased while expressions of HIF1alpha (p = 0.009) and VEGFR2 (p =
      0.081) were decreased at recurrence. Similarly, CXCL12 protein expression tended
      to increase (p = 0.096) while VEGFR2 staining was decreased (p = 0.004) at
      recurrence. An increase of anti-tumoral effect was observed with the combination
      of AMD3100 and RT/TMZ versus RT/TMZ alone in GB explants. Recurrence of GB after
      chemo-radiation could be associated with a switch of angiogenic pattern from
      VEGFR2-HIF1alpha to CXCL12-CXCR4 pathway, leading to new perspectives in
      angiogenic treatment. 

PMID- 25860929
TI  - FBXW7-mutated colorectal cancer cells exhibit aberrant expression of
      phosphorylated-p53 at Serine-15.
AB  - FBXW7 mutations occur in a variety of human cancers including colorectal cancer
      (CRC). Elucidating its mechanism of action has become crucial for cancer therapy;
      however, it is also complicated by the fact that FBXW7 can influence many
      pathways due to its role as an E3-ubiquitin ligase in proteasome degradation.
      FBXW7 and TP53 are tumour suppressors intensively implicated in colorectal
      carcinogenesis. Deletion mutations in these two genes in animal models mark the
      progression from adenoma to carcinoma. Although still largely unknown, the last
      defense mechanism against CRC at the molecular level could be through a
      synergistic effect of the two genes. The underlying mechanism requires further
      investigation. In our laboratory, we have used a phospho-kinase profiler array to
      illustrate a potential molecular link between FBXW7 and p53 in CRC cells. In
      vitro and in vivo assessments demonstrated aberrant induction of phosphorylated
      p53 at Serine 15 [phospho-p53(Ser15)] in human FBXW7-deficient CRC cells as
      compared to their FBXW7-wild-type counterparts. FBXW7 loss in HCT116 cells
      promoted resistance to oxaliplatin. Immunoblotting data further confirmed that
      reduction of phospho-p53(Ser15) may contribute to the decreased efficacy of
      therapy in FBXW7-mutated CRC cells. The findings may suggest the applicability of
      phospho-p53(Ser15) as an indicative marker of FBXW7-mutations. Phospho-p53(Ser15)
      regulation by FBXW7 E3-ligase activity could provide important clues for
      understanding FBXW7 behavior in tumour progression and grounds for its clinical
      applicability thereafter. 

PMID- 25860931
TI  - Marine compounds inhibit growth of multiple myeloma in vitro and in vivo.
AB  - PURPOSE: The prognosis of patients with multiple myeloma (MM) is still dismal
      despite recent improvements achieved by introducing new therapeutic agents.
      However, there remains an urgent need for progress in myeloma drug development.
      We here show that novel marine-derived compounds can exert potent anti-myeloma
      activity. EXPERIMENTAL DESIGN: Nine marine-derived compounds were applied at low
      nM concentrations (0.1-100 nM) to MM cell lines (OPM-2, NCI-H929, U266, RPMI
      8226), to primary human myeloma cells and to peripheral blood mononuclear cells.
      Apoptosis was determined by flow cytometry. In addition, eGFP-transgenic MM cell
      lines growing with mesenchymal cells from bone marrow were used to visualize
      tumors by fluorescence stereomicroscopy. Anti-myelomaactivities were studied in
      vitro in 3D spheroids and in vivo in myeloma xenografts on chicken embryos. Tumor
      size was analyzed by measuring GFP content with a GFP ELISA. Anti-angiogenic
      activities of compounds were tested in an in vivo gelatin sponge assay with
      conditioned media from primary bone marrow-derived endothelial cells. RESULTS: We
      identified a subset of marine compounds with strong anti-myeloma activity in
      vitro and in vivo. Moreover, some of the compounds inhibited myeloma-related
      angiogenesis in the in vivo gelatin sponge assay. They merit further drug
      development to improve treatment options for MM.

PMID- 25860930
TI  - The proto-oncogene c-Src and its downstream signaling pathways are inhibited by
      the metastasis suppressor, NDRG1.
AB  - N-myc downstream regulated gene-1 (NDRG1) is a potent metastasis suppressor that
      plays a key role in regulating signaling pathways involved in mediating cancer
      cell invasion and migration, including those derived from prostate, colon, etc.
      However, the mechanisms and molecular targets through which NDRG1 reduces cancer
      cell invasion and migration, leading to inhibition of cancer metastasis, are not
      fully elucidated. In this investigation, using NDRG1 over-expression models in
      three tumor cell-types (namely, DU145, PC3MM and HT29) and also NDRG1 silencing
      in DU145 and HT29 cells, we reveal that NDRG1 decreases phosphorylation of a key
      proto-oncogene, cellular Src (c-Src), at a well-characterized activating site
      (Tyr416). NDRG1-mediated down-regulation of EGFR expression and activation were
      responsible for the decreased phosphorylation of c-Src (Tyr416). Indeed, NDRG1
      prevented recruitment of c-Src to EGFR and c-Src activation. Moreover, NDRG1
      suppressed Rac1 activity by modulating phosphorylation of a c-Src downstream
      effector, p130Cas, and its association with CrkII, which acts as a "molecular
      switch" to activate Rac1. NDRG1 also affected another signaling molecule involved
      in modulating Rac1 signaling, c-Abl, which then inhibited CrkII phosphorylation.
      Silencing NDRG1 increased cell migration relative to the control and inhibition
      of c-Src signaling using siRNA, or a pharmacological inhibitor (SU6656),
      prevented this increase. Hence, the role of NDRG1 in decreasing cell migration
      is, in part, due to its inhibition of c-Src activation. In addition, novel
      pharmacological agents, which induce NDRG1 expression and are currently under
      development as anti-metastatic agents, markedly increase NDRG1 and decrease c-Src
      activation. This study leads to important insights into the mechanism involved in
      inhibiting metastasis by NDRG1 and how to target these pathways with novel
      therapeutics. 

PMID- 25860933
TI  - Role of ASXL1 and TP53 mutations in the molecular classification and prognosis of
      acute myeloid leukemias with myelodysplasia-related changes.
AB  - Acute myeloid leukemias (AML) with myelodysplasia-related changes (AML-MRC) are
      defined by the presence of multilineage dysplasia (MLD), and/or myelodysplastic
      syndrome (MDS)-related cytogenetics, and/or previous MDS. The goal of this study
      was to identify distinct biological and prognostic subgroups based on mutations
      of ASXL1, RUNX1, DNMT3A, NPM1, FLT3 and TP53 in 125 AML-MRC patients according to
      the presence of MLD, cytogenetics and outcome. ASXL1 mutations (n=26, 21%) were
      associated with a higher proportion of marrow dysgranulopoiesis (mutant vs. wild
      type: 75% vs. 55%, p=0.030) and were mostly found in intermediate cytogenetic AML
      (23/26) in which they predicted inferior 2-year overall survival (OS, mutant vs.
      wild-type: 14% vs. 37%, p=0.030). TP53 mutations (n=28, 22%) were mostly found in
      complex karyotype AML (26/28) and predicted poor outcome within unfavorable
      cytogenetic risk AML (mutant vs. wild-type: 9% vs. 40%, p=0.040). In multivariate
      analysis, the presence of either ASXL1 or TP53 mutation was the only independent
      factor associated with shorter OS (HR, 95%CI: 2.53, 1.40-4.60, p=0.002) while
      MLD, MDS-related cytogenetics and previous MDS history did not influence OS. We
      conclude that ASXL1 and TP53 mutations identify two molecular subgroups among AML
      MRCs, with specific poor prognosis. This could be useful for future diagnostic
      and prognostic classifications. 

PMID- 25860932
TI  - Controlled release microspheres loaded with BMP7 suppress primary tumors from
      human glioblastoma.
AB  - Glioblastoma tumor initiating cells are believed to be the main drivers behind
      tumor recurrence, and therefore therapies that specifically manage this
      population are of great medical interest. In a previous work, we synthesized
      controlled release microspheres optimized for intracranial delivery of BMP7, and
      showed that these devices are able to stop the in vitro growth of a glioma cell
      line. Towards the translational development of this technology, we now explore
      these microspheres in further detail and characterize the mechanism of action and
      the in vivo therapeutic potential using tumor models relevant for the clinical
      setting: human primary glioblastoma cell lines. Our results show that BMP7 can
      stop the proliferation and block the self-renewal capacity of those primary cell
      lines that express the receptor BMPR1B. BMP7 was encapsulated in poly (lactic-co
      glycolic acid) microspheres in the form of a complex with heparin and Tetronic,
      and the formulation provided effective release for several weeks, a process
      controlled by carrier degradation. Data from xenografts confirmed reduced and
      delayed tumor formation for animals treated with BMP7-loaded microspheres. This
      effect was coincident with the activation of the canonical BMP signaling pathway.
      Importantly, tumors treated with BMP7-loaded microspheres also showed
      downregulation of several markers that may be related to a malignant stem cell
      like phenotype: CD133(+), Olig2, and GFAPdelta. We also observed that tumors
      treated with BMP7-loaded microspheres showed enhanced expression of cell cycle
      inhibitors and reduced expression of the proliferation marker PCNA. In summary,
      BMP7-loaded controlled release microspheres are able to inhibit GBM growth and
      reduce malignancy markers. We envisage that this kind of selective therapy for
      tumor initiating cells could have a synergistic effect in combination with
      conventional cytoreductive therapy (chemo-, radiotherapy) or with immunotherapy.

PMID- 25860934
TI  - Loss of miR-200c up-regulates CYP1B1 and confers docetaxel resistance in renal
      cell carcinoma.
AB  - Despite high protein expression and enzymatic activity of cytochrome P450 1B1
      (CYP1B1) in renal cell cancer (RCC), its functional significance has not been
      elucidated. Here we explored the functional role and regulatory mechanism of
      CYP1B1 in RCC. Reduction of CYP1B1 levels fail to prevent in vitro tumorigenicity
      such as proliferation, apoptosis, and cell cycle progression of RCC cells.
      Moreover, the expression levels are not associated with tumor type, stage,
      Fuhrman grade and 5-year survival probability after surgery. Instead, alteration
      of CYP1B1 expression regulates the chemosensitivity of RCC cells to docetaxel
      suggesting its critical contribution to the chemoresistance. Additionally, miR
      200c, which is significantly down-regulated in RCC regulates CYP1B1 expression
      and activity. An inverse association was also observed between the expression
      levels of miR-200c and CYP1B1 protein in RCC tissues. Finally, alteration of miR
      200c levels affects the chemosensitivity of RCC cells. Restoration of docetaxel
      resistance by exogenous expression of CYP1B1 in miR-200c-over-expressing cells
      indicates that CYP1B1 is a functional target of miR-200c. These results suggest
      that CYP1B1 up-regulation mediated by low miR-200c is one of the mechanisms
      underlying resistance of RCC cells to docetaxel. Therefore, expression of CYP1B1
      and miR-200c in RCC may be useful as a prediction for docetaxel response.

PMID- 25860935
TI  - Endothelial exosomes contribute to the antitumor response during breast cancer
      neoadjuvant chemotherapy via microRNA transfer.
AB  - The interaction between tumor cells and their microenvironment is an essential
      aspect of tumor development. Therefore, understanding how this microenvironment
      communicates with tumor cells is crucial for the development of new anti-cancer
      therapies. MicroRNAs (miRNAs) are small non-coding RNAs that inhibit gene
      expression. They are secreted into the extracellular medium in vesicles called
      exosomes, which allow communication between cells via the transfer of their
      cargo. Consequently, we hypothesized that circulating endothelial miRNAs could be
      transferred to tumor cells and modify their phenotype. Using exogenous miRNA, we
      demonstrated that endothelial cells can transfer miRNA to tumor cells via
      exosomes. Using miRNA profiling, we identified miR-503, which exhibited
      downregulated levels in exosomes released from endothelial cells cultured under
      tumoral conditions. The modulation of miR-503 in breast cancer cells altered
      their proliferative and invasive capacities. We then identified two targets of
      miR-503, CCND2 and CCND3. Moreover, we measured increased plasmatic miR-503 in
      breast cancer patients after neoadjuvant chemotherapy, which could be partly due
      to increased miRNA secretion by endothelial cells. Taken together, our data are
      the first to reveal the involvement of the endothelium in the modulation of tumor
      development via the secretion of circulating miR-503 in response to chemotherapy
      treatment. 

PMID- 25860936
TI  - Increased angiogenesis is associated with a 32-gene expression signature and 6p21
      amplification in aggressive endometrial cancer.
AB  - BACKGROUND: Angiogenesis is a hallmark of cancer. The aim of this study was to
      explore whether microvessel proliferation is associated with gene expression
      profiles or copy number alterations in endometrial cancer. METHODS: A prospective
      series of endometrial carcinomas was studied for angiogenesis markers, gene
      expression profiles, and gene copy number data. For validation, an independent
      series of endometrial carcinomas as well as an external cohort of endometrial
      cancer patients were examined by gene expression microarrays. RESULTS: Increased
      microvessel proliferation (MVP) was associated with aggressive tumor features and
      reduced survival, and a 32-gene expression signature was found to separate tumors
      with high versus low MVP. An increased 32-gene signature score was confirmed to
      associate with high-grade tumor features and reduced survival by independent
      cohorts. Copy number studies revealed that amplification of the 6p21 region was
      significantly associated with MVP, a high 32-gene score, as well as reduced
      survival. CONCLUSION: Increased MVP was significantly associated with aggressive
      endometrial cancer and reduced survival. Integrated analyses demonstrated
      significant associations between increased vascular proliferation, amplification
      of the 6p21 region, VEGF-A mRNA expression, and the 32-gene angiogenesis
      signature. Our findings indicate amplification of 6p21 as a possible driver of
      tumor vascular proliferation in endometrial cancer.

PMID- 25860937
TI  - Elevated serum CA72-4 levels predict poor prognosis in pancreatic adenocarcinoma
      after intensity-modulated radiation therapy.
AB  - Carbohydrate antigen 72-4 (CA72-4) is a human tumor-associated glycoprotein,
      commonly used as a tumor marker for diagnosing and predicting outcome in gastric
      and ovarian cancers. However, the relationship between serum CA72-4 levels and
      prognosis of pancreatic adenocarcinoma has not been fully elucidated. A total of
      113 consecutive locally advanced pancreatic adenocarcinoma patients who underwent
      intensity-modulated radiation therapy (IMRT) with or without chemotherapy were
      enrolled in this study. Serum CA72-4 levels were analyzed using
      immunoenzymometric assays. The association between serum CA72-4 levels and
      prognosis was evaluated. Serum CA72-4 levels was related with lymph node
      metastasis (P<0.001). The median overall survival time was 14.0 months for
      patients with serum CA72-4 normal levels and 10.0 months for the elevated levels
      (P<0.001). Multivariate analysis identified that Serum CA72-4 concentration was a
      significant prognostic factor (P<0.001). The hazard ratio (HR) of elevated serum
      CA72-4 levels compared with normal serum CA72-4 levels was 2.34 (95% confidence
      interval [CI]: 1.46-3.73), after adjusted for gender and age. Based on this
      finding, Serum CA72-4 is a potential marker to predict lymph node metastasis and
      prognosis in pancreatic adenocarcinoma. 

PMID- 25860938
TI  - Targeting of surface alpha-enolase inhibits the invasiveness of pancreatic cancer
      cells.
AB  - Pancreatic Ductal Adenocarcinoma (PDAC) is a highly aggressive malignancy
      characterized by rapid progression, invasiveness and resistance to treatment. We
      have previously demonstrated that most PDAC patients have circulating antibodies
      against the glycolytic enzyme alpha-enolase (ENO1), which correlates with a
      better response to therapy and survival. ENO1 is a metabolic enzyme, also
      expressed on the cell surface where it acts as a plasminogen receptor. ENO1 play
      a crucial role in cell invasion and metastasis by promoting plasminogen
      activation into plasmin, a serine-protease involved in extracellular matrix
      degradation. The aim of this study was to investigate the role of ENO1 in PDAC
      cell invasion. We observed that ENO1 was expressed on the cell surface of most
      PDAC cell lines. Mouse anti-human ENO1 monoclonal antibodies inhibited
      plasminogen-dependent invasion of human PDAC cells, and their metastatic
      spreading in immunosuppressed mice was inhibited. Notably, a single
      administration of Adeno-Associated Virus (AAV)-expressing cDNA coding for 72/1
      anti-ENO1 mAb reduced the number of lung metastases in immunosuppressed mice
      injected with PDAC cells. Overall, these data indicate that ENO1 is involved in
      PDAC cell invasion, and that administration of an anti-ENO1 mAb can be exploited
      as a novel therapeutic option to increase the survival of metastatic PDAC
      patients. 

PMID- 25860939
TI  - Genomic analysis of xCT-mediated regulatory network: Identification of novel
      targets against AIDS-associated lymphoma.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent of
      primary effusion lymphoma (PEL), a rapidly progressing malignancy mostly arising
      in HIV-infected patients. Even under conventional chemotherapy, PEL continues to
      portend nearly 100% mortality within several months, which urgently requires
      novel therapeutic strategies. We have previously demonstrated that targeting xCT,
      an amino acid transporter for cystine/glutamate exchange, induces significant PEL
      cell apoptosis through regulation of multiple host and viral factors. More
      importantly, one of xCT selective inhibitors, Sulfasalazine (SASP), effectively
      prevents PEL tumor progression in an immune-deficient xenograft model. In the
      current study, we use Illumina microarray to explore the profile of genes altered
      by SASP treatment within 3 KSHV(+) PEL cell-lines, and discover that many genes
      involved in oxidative stress/antioxidant defense system, apoptosis/anti
      apoptosis/cell death, and cellular response to unfolded proteins/topologically
      incorrect proteins are potentially regulated by xCT. We further validate 2
      downstream candidates, OSGIN1 (oxidative stress-induced growth inhibitor 1) and
      XRCC5 (X-ray repair cross-complementing protein 5), and evaluate their functional
      relationship with PEL cell survival/proliferation and chemoresistance,
      respectively. Together, our data indicate that targeting these novel xCT
      regulated downstream genes may represent a promising new therapeutic strategy
      against PEL and/or other AIDS-related lymphoma.

PMID- 25860940
TI  - MYCN amplification confers enhanced folate dependence and methotrexate
      sensitivity in neuroblastoma.
AB  - MYCN amplification occurs in 20% of neuroblastomas and is strongly related to
      poor clinical outcome. We have identified folate-mediated one-carbon metabolism
      as highly upregulated in neuroblastoma tumors with MYCN amplification and have
      validated this finding experimentally by showing that MYCN amplified
      neuroblastoma cell lines have a higher requirement for folate and are
      significantly more sensitive to the antifolate methotrexate than cell lines
      without MYCN amplification. We have demonstrated that methotrexate uptake in
      neuroblastoma cells is mediated principally by the reduced folate carrier (RFC;
      SLC19A1), that SLC19A1 and MYCN expression are highly correlated in both patient
      tumors and cell lines, and that SLC19A1 is a direct transcriptional target of N
      Myc. Finally, we assessed the relationship between SLC19A1 expression and patient
      survival in two independent primary tumor cohorts and found that SLC19A1
      expression was associated with increased risk of relapse or death, and that
      SLC19A1 expression retained prognostic significance independent of age, disease
      stage and MYCN amplification. This study adds upregulation of folate-mediated one
      carbon metabolism to the known consequences of MYCN amplification, and suggests
      that this pathway might be targeted in poor outcome tumors with MYCN
      amplification and high SLC19A1 expression. 

PMID- 25860941
TI  - Walking paths to and from a goal differ: on the role of bearing angle in the
      formation of human locomotion paths.
AB  - The path that humans take while walking to a goal is the result of a cognitive
      process modulated by the perception of the environment and physiological
      constraints. The path shape and timing implicitly embeds aspects of the
      architecture behind this process. Here, locomotion paths were investigated during
      a simple task of walking to and from a goal, by looking at the evolution of the
      position of the human on a horizontal (x,y) plane. We found that the path while
      walking to a goal was not the same as that while returning from it. Forward
      return paths were systematically separated by 0.5-1.9m, or about 5% of the goal
      distance. We show that this path separation occurs as a consequence of
      anticipating the desired body orientation at the goal while keeping the target in
      view. The magnitude of this separation was strongly influenced by the bearing
      angle (difference between body orientation and angle to goal) and the final
      orientation imposed at the goal. This phenomenon highlights the impact of a trade
      off between a directional perceptual apparatus-eyes in the head on the shoulders
      and and physiological limitations, in the formation of human locomotion paths.
      Our results give an insight into the influence of environmental and perceptual
      variables on human locomotion and provide a basis for further mathematical study
      of these mechanisms. 

PMID- 25860942
TI  - Modeling the lexical morphology of Western handwritten signatures.
AB  - A handwritten signature is the final response to a complex cognitive and
      neuromuscular process which is the result of the learning process. Because of the
      many factors involved in signing, it is possible to study the signature from many
      points of view: graphologists, forensic experts, neurologists and computer vision
      experts have all examined them. Researchers study written signatures for
      psychiatric, penal, health and automatic verification purposes. As a potentially
      useful, multi-purpose study, this paper is focused on the lexical morphology of
      handwritten signatures. This we understand to mean the identification, analysis,
      and description of the signature structures of a given signer. In this work we
      analyze different public datasets involving 1533 signers from different Western
      geographical areas. Some relevant characteristics of signature lexical morphology
      have been selected, examined in terms of their probability distribution functions
      and modeled through a General Extreme Value distribution. This study suggests
      some useful models for multi-disciplinary sciences which depend on handwriting
      signatures. 

PMID- 25860943
TI  - Matrix-assisted laser desorption/ionization time of flight mass-spectrometry
      (MALDI-TOF MS) based typing of extended-spectrum beta-lactamase producing E. coli
      -a novel tool for real-time outbreak investigation.
AB  - Epidemiologically linked clusters are confirmed by typing strains with molecular
      typing such as pulsed-field gel electrophoresis (PFGE). We compared six extended
      spectrum beta-lactamase producing E. coli of a PFGE-related cluster with Matrix
      assisted laser desorption/ionization-time of flight mass-spectrometry based
      typing that confirmed relatedness faster and more cost-effective, but as reliable
      as PFGE. 

PMID- 25860944
TI  - Antiproliferative, antibacterial and antifungal activity of the lichen Xanthoria
      parietina and its secondary metabolite parietin.
AB  - Lichens are valuable natural resources used for centuries throughout the world as
      medicine, food, fodder, perfume, spices and dyes, as well as for other
      miscellaneous purposes. This study investigates the antiproliferative,
      antibacterial and antifungal activity of the acetone extract of the lichen
      Xanthoria parietina (Linnaeus) Theodor Fries and its major secondary metabolite,
      parietin. The extract and parietin were tested for antimicrobial activity against
      nine American Type Culture Collection standard and clinically isolated bacterial
      strains, and three fungal strains. Both showed strong antibacterial activity
      against all bacterial strains and matched clinical isolates, particularly against
      Staphylococcus aureus from standard and clinical sources. Among the fungi tested,
      Rhizoctonia solani was the most sensitive. The antiproliferative effects of the
      extract and parietin were also investigated in human breast cancer cells. The
      extract inhibited proliferation and induced apoptosis, both effects being
      accompanied by modulation of expression of cell cycle regulating genes such as
      p16, p27, cyclin D1 and cyclin A. It also mediated apoptosis by activating
      extrinsic and intrinsic cell death pathways, modulating Tumor Necrosis Factor
      related apoptosis-inducing ligand (TRAIL) and B-cell lymphoma 2 (Bcl-2), and
      inducing Bcl-2-associated agonist of cell death (BAD) phosphorylation. Our
      results indicate that Xanthoria parietina is a major potential source of
      antimicrobial and anticancer substances. 

PMID- 25860945
TI  - APOE polymorphisms contribute to reduced atorvastatin response in Chilean
      Amerindian subjects.
AB  - Genetic factors can determine the high variability observed in response to lipid
      lowering therapy with statins. Nonetheless, the frequency of single nucleotide
      polymorphisms (SNPs) and their impact can vary due to ethnicity. Because the
      Chilean population carries a strong Amerindian background, the objective of this
      study was to evaluate the influence of apolipoprotein E (APOE) variants
      (rs429358, rs7412) and the 1959C>T SNP (rs5925) in the low-density lipoprotein
      receptor (LDLR) in response to atorvastatin treatment in hypercholesterolemic
      individuals. A hundred and thirty nine subjects undergoing statin therapy were
      included. Identification of Amerindian mtDNA haplogroups was determined by
      polymerase chain reaction (PCR) and PCR followed by restriction fragment length
      polymorphism (RFLP), respectively. SNPs were determined by PCR-RFLP. Out of the
      139 individuals studied, 84.4% had an Amerindian background, according to mtDNA
      analysis. In relation to APOE variants, carriers of the E3/4 genotype presented
      lower cholesterol reduction compared to genotype E3/3 (LDL-C: -18% vs. -29%, p ?
      0.001). On the other hand, the LDLR rs5925 SNP was not related to atorvastatin
      response (p = 0.5760). Our results suggest that APOE SNPs are potential
      predictors to atorvastatin therapy in Amerindian Chilean subjects. 

PMID- 25860946
TI  - Posttraumatic inflammation as a key to neuroregeneration after traumatic spinal
      cord injury.
AB  - Pro- and anti-inflammatory cytokines might have a large impact on the secondary
      phase and on the neurological outcome of patients with acute spinal cord injury
      (SCI). We measured the serum levels of different cytokines (Interferon-gamma,
      Tumor Necrosis Factor-alpha, Interleukin-1beta, IL-6, IL-8, IL-10, and Vascular
      Endothelial Growth Factor) over a 12-week period in 40 acute traumatic SCI
      patients: at admission on average one hour after initial trauma; at four, nine,
      12, and 24 h; Three, and seven days after admission; and two, four, eight, and
      twelve weeks after admission. This was done using a Luminex Performance Human
      High Sensitivity Cytokine Panel. SCI was classified using the American Spinal
      Injury Association (ASIA) Impairment Scale (AIS) at time of admission and after
      12 weeks. TNFalpha, IL-1beta, IL-6, IL-8, and IL-10 concentrations were
      significantly higher in patients without neurological remission and in patients
      with an initial AIS A (p < 0.05). This study shows significant differences in
      cytokine concentrations shown in traumatic SCI patients with different
      neurological impairments and within a 12-week period. IL-8 and IL-10 are
      potential peripheral markers for neurological remission and rehabilitation after
      traumatic SCI. Furthermore our cytokine expression pattern of the acute,
      subacute, and intermediate phase of SCI establishes a possible basis for future
      studies to develop standardized monitoring, prognostic, and tracking techniques. 

PMID- 25860947
TI  - Pathogenesis of renal disease in systemic lupus erythematosus--the role of
      autoantibodies and lymphocytes subset abnormalities.
AB  - Lupus nephritis (LN) is a common and severe organ manifestation of systemic lupus
      erythematosus (SLE), and is associated with significant patient morbidity and
      mortality. Autoantibodies and aberrations in lymphocyte subsets have putative
      roles in the pathogenesis of SLE and LN, and might reflect disease activity and
      are amenable to immunosuppressive treatments. Anti-DNA is one of the well-studied
      autoantibodies, which correlates with disease activity and has direct
      nephritogenic effects on resident renal cells and various glomerular components.
      Other important autoantibodies in the pathogenesis of LN include anti-C1q, anti
      alpha-actinin and anti-nucleosome antibodies. Changes in naive and memory B cells
      and plasma cells have been observed in SLE and LN patients. These B cell subsets
      exert diverse effects during pathogenesis of LN such as production of
      autoantibodies, secretion of proinflammatory and anti-inflammatory cytokines and
      presentation of auto-antigens to effector cells. Aberration of T lymphocytes,
      especially the T-helper subsets, is also highly pertinent in the development of
      LN. In this context, important T helper subsets include Th1, Th2, Th9, Th17, TReg
      and follicular T-helper cells. The growing knowledge on these autoantibodies and
      lymphocyte subset abnormalities will enhance our understanding of SLE and LN, and
      hence help devise better strategies for disease monitoring and treatment. 

PMID- 25860948
TI  - Promotion of Ni2+ removal by masking toxicity to sulfate-reducing bacteria:
      addition of citrate.
AB  - The sulfate-reducing bioprocess is a promising technology for the treatment of
      heavy metal-containing wastewater. This work was conducted to investigate the
      possibility of promoting heavy metal removal by the addition of citrate to mask
      Ni2+ toxicity to sulfate-reducing bacteria (SRB) in batch reactors. SRB growth
      was completely inhibited in Ni2+-containing medium (1 mM) when lactate served as
      the sole carbon resource, leading to no sulfate reduction and Ni2+ removal.
      However, after the addition of citrate, SRB grew well, and sulfate was quickly
      reduced to sulfide. Simultaneously, the Ni-citrate complex was biodegraded to
      Ni2+ and acetate. The NiS precipitate was then formed, and Ni2+ was completely
      removed from the solution. It was suggested that the addition of citrate greatly
      alleviates Ni2+ toxicity to SRB and improves the removal of Ni2+, which was
      confirmed by quantitative real-time PCR targeting dissimilatory sulfite reductase
      (dsrAB) genes. Analysis of the carbon metabolism indicated that lactate instead
      of acetate served as the electron donor for sulfate reduction. This study offers
      a potential approach to increase the removal of heavy metals from wastewater in
      the single stage SRB-based bioprocess. 

PMID- 25860949
TI  - Psoralea glandulosa as a potential source of anticancer agents for melanoma
      treatment.
AB  - With the aim of identifying novel agents with antigrowth and pro-apoptotic
      activity on melanoma cancer, the present study was undertaken to investigate the
      biological activity of the resinous exudate of aerial parts from Psoralea
      glandulosa, and its active components (bakuchiol (1), 3-hydroxy-bakuchiol (2) and
      12-hydroxy-iso-bakuchiol (3)) against melanoma cells (A2058). In addition, the
      effect in cancer cells of bakuchiol acetate (4), a semi-synthetic derivative of
      bakuchiol, was examined. The results obtained show that the resinous exudate
      inhibited the growth of cancer cells with IC50 value of 10.5 MUg/mL after 48 h of
      treatment, while, for pure compounds, the most active was the semi-synthetic
      compound 4. Our data also demonstrate that resin is able to induce apoptotic cell
      death, which could be related to an overall action of the meroterpenes present.
      In addition, our data seem to indicate that the apoptosis correlated to the
      tested products appears, at least in part, to be associated with an increase of
      reactive oxygen species (ROS) production. In summary, our study provides the
      first evidence that P. glandulosa may be considered a source of useful molecules
      in the development of analogues with more potent efficacy against melanoma cells.

PMID- 25860950
TI  - Synthesis of spongy-like mesoporous hydroxyapatite from raw waste eggshells for
      enhanced dissolution of ibuprofen loaded via supercritical CO2.
AB  - The use of cheaper and recyclable biomaterials (like eggshells) to synthesize
      high purity hydroxyapatite (HAp) with better properties (small particle size,
      large surface area and pore volume) for applications (in environmental
      remediation, bone augmentation and replacement, and drug delivery systems) is
      vital since high-purity synthetic calcium sources are expensive. In this work,
      pure and mesoporous HAp nanopowder with large pore volume (1.4 cm3/g) and surface
      area (284.1 m2/g) was produced from raw eggshells at room temperature using a
      simple two-step procedure. The control of precursor droplets could stabilize the
      pH value of the reaction solution, because of the size of the needle (of the
      syringe pump used for precursor additions) leading to production of HAp with high
      surface area and pore size. The as-produced HAp revealed high ibuprofen (as a
      model drug) loading (1.38 g/g HAp), enhanced dissolution and controllable release
      of the drug via solute-saturated supercritical carbon dioxide. 

PMID- 25860951
TI  - RNA sequencing identifies upregulated kyphoscoliosis peptidase and phosphatidic
      acid signaling pathways in muscle hypertrophy generated by transgenic expression
      of myostatin propeptide.
AB  - Myostatin (MSTN), a member of the transforming growth factor-beta superfamily,
      plays a crucial negative role in muscle growth. MSTN mutations or inhibitions can
      dramatically increase muscle mass in most mammal species. Previously, we
      generated a transgenic mouse model of muscle hypertrophy via the transgenic
      expression of the MSTN N-terminal propeptide cDNA under the control of the
      skeletal muscle-specific MLC1 promoter. Here, we compare the mRNA profiles
      between transgenic mice and wild-type littermate controls with a high-throughput
      RNA sequencing method. The results show that 132 genes were significantly
      differentially expressed between transgenic mice and wild-type control mice; 97
      of these genes were up-regulated, and 35 genes were down-regulated in the
      skeletal muscle. Several genes that had not been reported to be involved in
      muscle hypertrophy were identified, including up-regulated myosin binding protein
      H (mybph), and zinc metallopeptidase STE24 (Zmpste24). In addition,
      kyphoscoliosis peptidase (Ky), which plays a vital role in muscle growth, was
      also up-regulated in the transgenic mice. Interestingly, a pathway analysis based
      on grouping the differentially expressed genes uncovered that cardiomyopathy
      related pathways and phosphatidic acid (PA) pathways (Dgki, Dgkz, Plcd4) were up
      regulated. Increased PA signaling may increase mTOR signaling, resulting in
      skeletal muscle growth. The findings of the RNA sequencing analysis help to
      understand the molecular mechanisms of muscle hypertrophy caused by MSTN
      inhibition. 

PMID- 25860953
TI  - The Hit and Away technique: optimal usage of the ultrasonic scalpel in
      laparoscopic gastrectomy.
AB  - BACKGROUND: Thermal injury and unexpected bleeding caused by ultrasonic scalpels
      can lead to fatal complications in laparoscopic gastrectomy (LG), such as
      postoperative pancreatic fistulas (POPF). In this study, we developed the "Hit
      and Away" protocol for optimal usage of the ultrasonic scalpel, which in essence
      involves dividing tissues and vessels in batches using the tip of the scalpel to
      control tissue temperature. METHODS: To assess the effectiveness of the
      technique, the surface temperature of the mesocolon of female swine after
      ultrasonic scalpel activations was measured, and tissue samples were collected to
      evaluate microscopic thermal injury to the pancreas. In parallel, we
      retrospectively surveyed 216 patients who had undergone LG before or after the
      introduction of this technique and assessed the ability of this technique to
      reduce POPF. RESULTS: The tissue temperature of the swine mesocolon reached 43 
      degrees C, a temperature at which adipose tissue melted but fibrous tissue,
      including vessels, remained intact. The temperature returned to baseline within 3
      s of turning off the ultrasonic scalpel, demonstrating the advantage of using
      ultrasonic scalpel in a pulsatile manner. Tissue samples from the pancreas
      demonstrated that the extent of thermal injury post-procedure was limited to the
      capsule of the pancreas. Moreover, with respect to the clinical outcomes before
      and after the introduction of this technique, POPF incidence decreased
      significantly from 7.8 to 1.0% (p = 0.021). CONCLUSION: The "Hit and Away"
      technique can reduce blood loss and thermal injury to the pancreas and help to
      ensure the safety of lymph node dissection in LG.

PMID- 25860952
TI  - Endoscopic-assisted laparoscopic resection for gastric subepithelial tumors.
AB  - BACKGROUND: Laparoscopic resection is considered the treatment of choice for
      gastric subepithelial tumors. Occasionally, it is necessary to perform an
      intraoperative gastroscopy to localize the lesion. There are no data in the
      literature addressing the factors that can predict when a combined laparoscopic
      endoscopic approach will be needed. METHODS: A retrospective cohort study using a
      prospectively collected database was conducted. From January 2005 to December
      2013, all the patients undergoing a laparoscopic gastric resection for
      subepithelial tumors irresectable by endoscopy were reviewed. Potential
      predictive factors for the need of an intraoperative endoscopy were analyzed.
      RESULTS: Thirty-eight consecutive patients (22 men and 16 women) with a mean age
      of 67 (41-86) years underwent laparoscopic gastric resection for subepithelial
      tumors. Fourteen (36.8%) patients required intraoperative endoscopic assessment.
      The only significant factors related to the need of endoscopic assessment during
      surgery were tumor growth pattern (P = 0.002) and size (P = 0.001). CONCLUSIONS:
      An accurate description of tumor growth pattern and size by EUS is recommended in
      the preoperative assessment of gastric subepithelial tumors. Small tumors (<=18
      mm) with an intraluminal growth may need a combined endoscopic-assisted
      laparoscopic management.

PMID- 25860954
TI  - Regulation and methylation of tumor suppressor miR-124 by androgen receptor in
      prostate cancer cells.
AB  - Prostate cancer (PCa) is the most frequently diagnosed cancer for men in the
      developed world. Androgen receptor signaling pathway plays an important role in
      prostate cancer progression. Recent studies show that microRNA miR-124 exerts a
      tumor suppressive function in prostate cancer. However, the relationship between
      AR and miR-124 is unclear. In the present study, we found a negative feedback
      loop between AR and miR-124 expression. On one hand, miR-124 was a positively
      regulated target gene of the AR, on the other hand, overexpression of miR-124
      inhibited the expression of AR. In addition, we found that miR-124-2 and miR-124
      3 promoters were hypermethylated in AR-negative PCa cells. Furthermore,
      overexpression of miR-124 inhibited proliferation rates and invasiveness capacity
      of PCa cells in vitro, and suppressed xenograft tumor growth in vivo. Taken
      together, our results support a negative feedback loop between AR and miR-124
      expression. Methylation of miR-124-2 and miR-124-3 may serve as a biomarker for
      AR-negative PCa cells, and overexpression of miR-124 might be of potential
      therapeutic value for the treatment of PCa. 

PMID- 25860955
TI  - Fibroblast growth factor receptor 4 polymorphism is associated with liver
      cirrhosis in hepatocarcinoma.
AB  - BACKGROUND: Fibroblast growth factor receptor 4 (FGFR4) polymorphisms are
      positively correlated with tumor progression in numerous malignant tumors.
      However, the association between FGFR4 genetic variants and the risk of
      hepatocellular carcinoma (HCC) has not yet been determined. In this study, we
      investigated the potential associations of FGFR4 single nucleotide polymorphisms
      (SNPs) with HCC susceptibility and its clinicopathological characteristics.
      METHODOLOGY/PRINCIPAL FINDINGS: Four SNPs in FGFR4 (rs1966265, rs351855,
      rs2011077, and rs7708357) were analyzed among 884 participants, including 595
      controls and 289 patients with HCC. The samples were further analyzed to clarify
      the associations between these gene polymorphisms and the risk of HCC, and the
      impact of these SNPs on the susceptibility and clinicopathological
      characteristics of HCC. After adjusting for other covariants, HCC patients who
      carrying at least one A genotype (GA and AA) at rs351855 were observed to have a
      higher risk of liver cirrhosis compared with those carrying the wild-type
      genotype (GG) (OR: 2.113, 95% CI: 1.188-3.831). Moreover, the patients with at
      least one A genotype were particularly showed a high level of alpha-fetoprotein
      (AFP). CONCLUSIONS: Our findings suggest that genetic polymorphism in FGFR4
      rs351855 may be associated with the risk of HCC coupled with liver cirrhosis and
      may markedly increase the AFP level in Taiwanese patients with HCC. In addition,
      this is the first study that evaluated the risk factors associated with FGFR4
      polymorphism variants in Taiwanese patients with HCC.

PMID- 25860956
TI  - Overexpression of the Receptor for Advanced Glycation Endproducts (RAGE) is
      associated with poor prognosis in gastric cancer.
AB  - BACKGROUND: The receptor for advanced glycation endproducts (RAGE) is an
      oncogenic multidisciplinary trans-membranous receptor, which is overexpressed in
      multiple human cancers. Recently, it has been shown that RAGE is also involved in
      carcinogenesis and tumor invasion. In this study, we investigated the expression
      levels and prognostic value of RAGE in primary gastric cancers (GC). METHODS: We
      investigated RAGE expression in primary GC and paired normal gastric tissue by
      real-time quantitative RT-PCR (n = 30) and Western blotting analysis (n = 30).
      Additionally, we performed immunohistochemistry on 180 paraffin-embedded GC
      specimens, 69 matched normal specimens. RESULTS: RAGE was overexpressed in GC
      compared with the adjacent noncancerous tissues (P<0.001), and higher RAGE
      expression significantly correlated with the histological grade (P = 0.002),
      nodal status(P = 0.025), metastasis status(P = 0.002), and American Joint
      Committee on Cancer stage (P = 0.020). Furthermore, upregulation of RAGE
      expression is an independent prognostic factor in multivariate analysis using the
      Cox regression model (P = 0.001). CONCLUSIONS: RAGE Overexpression may be a
      useful marker to predict GC progression and poor prognosis.

PMID- 25860958
TI  - Correction: Antiapoptotic factor humanin is expressed in normal and tumoral
      pituitary cells and protects them from TNF-alpha-induced apoptosis.

PMID- 25860959
TI  - Filled pause refinement based on the pronunciation probability for lecture
      speech.
AB  - Nowadays, although automatic speech recognition has become quite proficient in
      recognizing or transcribing well-prepared fluent speech, the transcription of
      speech that contains many disfluencies remains problematic, such as spontaneous
      conversational and lecture speech. Filled pauses (FPs) are the most frequently
      occurring disfluencies in this type of speech. Most recent studies have shown
      that FPs are widely believed to increase the error rates for state-of-the-art
      speech transcription, primarily because most FPs are not well annotated or
      provided in training data transcriptions and because of the similarities in
      acoustic characteristics between FPs and some common non-content words. To
      enhance the speech transcription system, we propose a new automatic refinement
      approach to detect FPs in British English lecture speech transcription. This
      approach combines the pronunciation probabilities for each word in the dictionary
      and acoustic language model scores for FP refinement through a modified speech
      recognition forced-alignment framework. We evaluate the proposed approach on the
      Reith Lectures speech transcription task, in which only imperfect training
      transcriptions are available. Successful results are achieved for both the
      development and evaluation datasets. Acoustic models trained on different styles
      of speech genres have been investigated with respect to FP refinement. To further
      validate the effectiveness of the proposed approach, speech transcription
      performance has also been examined using systems built on training data
      transcriptions with and without FP refinement. 

PMID- 25860957
TI  - ING5 is phosphorylated by CDK2 and controls cell proliferation independently of
      p53.
AB  - Inhibitor of growth (ING) proteins have multiple functions in the control of cell
      proliferation, mainly by regulating processes associated with chromatin
      regulation and gene expression. ING5 has been described to regulate aspects of
      gene transcription and replication. Moreover deregulation of ING5 is observed in
      different tumors, potentially functioning as a tumor suppressor. Gene
      transcription in late G1 and in S phase and replication is regulated by cyclin
      dependent kinase 2 (CDK2) in complex with cyclin E or cyclin A. CDK2 complexes
      phosphorylate and regulate several substrate proteins relevant for overcoming the
      restriction point and promoting S phase. We have identified ING5 as a novel CDK2
      substrate. ING5 is phosphorylated at a single site, threonine 152, by cyclin
      E/CDK2 and cyclin A/CDK2 in vitro. This site is also phosphorylated in cells in a
      cell cycle dependent manner, consistent with it being a CDK2 substrate.
      Furthermore overexpression of cyclin E/CDK2 stimulates while the CDK2 inhibitor
      p27KIP1 represses phosphorylation at threonine 152. This site is located in a
      bipartite nuclear localization sequence but its phosphorylation was not
      sufficient to deregulate the subcellular localization of ING5. Although ING5
      interacts with the tumor suppressor p53, we could not establish p53-dependent
      regulation of cell proliferation by ING5 and by phospho-site mutants. Instead we
      observed that the knockdown of ING5 resulted in a strong reduction of
      proliferation in different tumor cell lines, irrespective of the p53 status. This
      inhibition of proliferation was at least in part due to the induction of
      apoptosis. In summary we identified a phosphorylation site at threonine 152 of
      ING5 that is cell cycle regulated and we observed that ING5 is necessary for
      tumor cell proliferation, without any apparent dependency on the tumor suppressor
      p53. 

PMID- 25860960
TI  - Correction: partially redundant enhancers cooperatively maintain Mammalian pomc
      expression above a critical functional threshold.

PMID- 25860961
TI  - Correction: Diets containing sea cucumber (Isostichopus badionotus) meals are
      hypocholesterolemic in young rats.

PMID- 25860962
TI  - Sialyltransferase7A, a Klf4-responsive gene, promotes cardiomyocyte apoptosis
      during myocardial infarction.
AB  - Myocardial infarction (MI) is one major cause of heart failure through its
      induction of cardiomyocyte death. However, the molecular mechanisms associated
      with MI-induced cardiomyocyte apoptosis in the context of sialylation of heart
      are not yet understood. In this study, we found that sialyltransferase7A
      (Siat7A), one of the members of sialyltransferase family, was significantly
      increased in the ischemic myocardium, as well as in the human cardiomyocyte cell
      line AC16 under hypoxic condition. The Sialyl-Tn antigen (Neu5Acalpha2-6GalNAc-O
      Ser/Thr) synthesized by Siat7A also increased in the AC16 cardiomyocytes
      following hypoxic stimulus. Increased Siat7A promoted cardiomyocyte apoptosis.
      The knockdown of Siat7A expression reduced cardiomyocyte apoptosis in both of
      vivo and vitro. Furthermore, the decreased extracellular signal-regulated kinase
      ERK1 and ERK2 (ERK1/2) activity was involved in the Siat7A-induced cardiomyocyte
      apoptosis. Notably, we showed that Kruppel-like factor 4 (Klf4), one of the
      transcription factors, specifically bound to the Siat7A promoter by ChIP assays.
      Deletion and mutagenesis analysis identified that Klf4 could transactivate the
      Siat7A promoter region (nt -655 to -636 bp). The upregulated Siat7A expression,
      which was paralleled by the increased Klf4 in the ischemic myocardium,
      contributed to cardiomyocyte apoptosis. Our study suggests Siat7A could be a
      valuable target for developing treatments for MI patients.

PMID- 25860964
TI  - Prevalence and correlates of hashish use in a national sample of high school
      seniors in the United States.
AB  - BACKGROUND: Cannabis (marijuana) use and acceptance towards use are increasing in
      the US, and state-level policies are becoming more liberal. A wealth of research
      has been conducted to examine risk factors for use; however, studies rarely
      differentiate between different forms of marijuana. OBJECTIVE: We sought to
      determine prevalence of use and delineate who is at risk for use of hashish, a
      more potent form of marijuana. METHODS: We examined data from a nationally
      representative sample of high school seniors in the Monitoring the Future study
      (2007-2011; weighted n = 10 597). We determined how sociodemographic factors and
      reasons for marijuana use correlated with recent (12 month) hashish use. RESULTS:
      Prevalence of recent hashish use was 6.5% and it was used by 18.3% of recent
      marijuana users. Hashish and other marijuana use tended to share many of the same
      correlates; however, associations were often stronger for hashish use. Females
      were consistently at low risk for use and users of other drugs were consistently
      at high risk for use. Black students tended to be at low risk for hashish use.
      Low risk of identifying as Hispanic or religious and high risk of higher personal
      income or going out more evenings per week for fun disappeared when controlling
      for other drug use. Using marijuana because the student felt he/she was "hooked"
      nearly doubled the odds for hashish use. CONCLUSIONS: This was the first national
      study to examine prevalence and correlates of hashish use. These findings can
      inform prevention in a time of increasing popularity of marijuana use.

PMID- 25860963
TI  - Polycyclic aromatic hydrocarbons reciprocally regulate IL-22 and IL-17 cytokines
      in peripheral blood mononuclear cells from both healthy and asthmatic subjects.
AB  - Pollution, including polycyclic aromatic hydrocarbons (PAH), may contribute to
      increased prevalence of asthma. PAH can bind to the Aryl hydrocarbon Receptor
      (AhR), a transcription factor involved in Th17/Th22 type polarization. These
      cells produce IL17A and IL-22, which allow neutrophil recruitment, airway smooth
      muscle proliferation and tissue repair and remodeling. Increased IL-17 and IL-22
      productions have been associated with asthma. We hypothesized that PAH might
      affect, through their effects on AhR, IL-17 and IL-22 production in allergic
      asthmatics. Activated peripheral blood mononuclear cells (PBMCs) from 16
      nonallergic nonasthmatic (NA) and 16 intermittent allergic asthmatic (AA)
      subjects were incubated with PAH, and IL-17 and IL-22 productions were assessed.
      At baseline, activated PBMCs from AA exhibited an increased IL-17/IL-22 profile
      compared with NA subjects. Diesel exhaust particle (DEP)-PAH and Benzo[a]Pyrene
      (B[a]P) stimulation further increased IL-22 but decreased IL-17A production in
      both groups. The PAH-induced IL-22 levels in asthmatic patients were
      significantly higher than in healthy subjects. Among PBMCs, PAH-induced IL-22
      expression originated principally from single IL-22- but not from IL-17-
      expressing CD4 T cells. The Th17 transcription factors RORA and RORC were down
      regulated, whereas AhR target gene CYP1A1 was upregulated. IL-22 induction by DEP
      PAH was mainly dependent upon AhR whereas IL-22 induction by B[a]P was dependent
      upon activation of PI3K and JNK. Altogether, these data suggest that DEP-PAH and
      B[a]P may contribute to increased IL22 production in both healthy and asthmatic
      subjects through mechanisms involving both AhR -dependent and -independent
      pathways. 

PMID- 25860965
TI  - Editorial: Drug Delivery Australia.

PMID- 25860966
TI  - Evaluation of bone targeting salmon calcitonin analogues in rats developing
      osteoporosis and adjuvant arthritis.
AB  - Synthetic analogues of the peptide hormone calcitonin have been used in medicine
      as biologic drug therapies for decades, to treat pathological conditions of
      excessive bone turnover, such as osteoporosis, where more bones are removed than
      replaced during bone remodeling. Osteoporosis and other chronic skeletal
      diseases, including inflammatory arthritis, exact a substantial and growing toll
      on aging populations worldwide however they respond poor to synthetic biologic
      drug therapy, due in part to the rapid half-life of elimination, which for
      calcitonin is 43 minutes. To address those shortcomings, we have developed and
      synthesized bone-targeting variants of calcitonin as a targeted drug delivery
      strategy, by conjugation to bisphosphonate drug bone-seeking functional groups in
      highly specific reaction conditions. To evaluate their in vivo efficacy,
      bisphosphonate-mediated bone targeting with PEGylated (polyethylene glycol
      conjugated) and non-PEGylated salmon calcitonin analogues were synthesized and
      dose escalation was performed in female rats developing Osteoporosis. The bone
      targeting calcitonin analogues were also tested in a separate cohort of male rats
      developing adjuvant-induced arthritis. Ovariectomized female rats developing
      Osteoporosis were administered daily sub-cutaneous injection of analogues
      equivalent to 5, 10 and 20 IU/kg of calcitonin for 3 months. Adjuvant arthritis
      was developed in male rats by administering Mycobacterium butyricum through tail
      base injection. Daily sub-cutaneous injection of analogues equivalent to 20 IU/kg
      of calcitonin was administered and the rats were measured for visible signs of
      inflammation to a 21 day endpoint. In both studies, the effect of drug
      intervention upon bone volume and bone mineral density (BMD) was assessed by
      measuring the trabecular bone volume percentage and BMD at the proximal tibial
      metaphysis using in vivo micro-computed tomography. With dose escalation studies,
      only bone targeting analogue dosed groups showed a trend towards increased BMD
      and bone volume at 4, 8 and 12 weeks. Significant preservation of bone volume and
      BMD as evidenced by nonsignificant (P<0.05) loss of bone volume and BMD at the
      end of 3 month study endpoint was seen in animals dosed with 20 IU/kg of
      calcitonin compounds. Similarly, in case of adjuvant-induced arthritis rats,
      there was a significant increase (P<0.05) in bone volume and BMD in calcitonin
      bisphosphonate and calcitonin-PEG-bisphosphonate treated groups at 21 days
      compared to the baseline values. Improved efficacy in terms of preserving bone
      volume and BMD in Osteoporosis, and in rats developing adjuvant-induced
      arthritis, by these analogues suggests their potential as new drug candidates for
      further evaluation to determine their usefulness in bone diseases characterized
      by excessive bone resorption. 

PMID- 25860967
TI  - Importance of operational factors in the reproducibility of Aspergillus
      galactomannan enzyme immune assay.
AB  - BACKGROUND: The Platelia Aspergillus Ag assay (Bio-Rad) is designed for detecting
      Aspergillus galactomannan (GM) and is widely used for diagnosing invasive
      aspergillosis but is hampered by variable occurrences of unreproducible positive
      results. Frequency and origin of these unreproducible results have not been
      formally studied. METHODS: Different technicians simultaneously performed four
      tests on 550 consecutive sera from adult patients (Test#1-Test#2 for extraction#1
      and Test#3-Test#4 for extraction#2). The samples were classified as confirmed
      negative [all tests with GM optical density index (GM-ODI) <0.5], confirmed
      positive (all tests with GM-ODI >=0.5), extraction unreproducible positive
      (Test#1 and Test#2 ODIs >=0.5, and Test#3 and Test#4 GM-ODIs <0.5, or
      conversely), and ELISA unreproducible positive (only one test with GM-ODI >=0.5).
      The samples with positive and negative GM-ODIs within the assay coefficient of
      variation values were classified as non-conclusive. Four similar additional tests
      were performed after <=72h storage at 4  degrees C and a new GM test after 8
      months at -20  degrees C. RESULTS: Five-hundred-twenty sera (94.5%) were
      confirmed negative, 15 (2.7%) confirmed positive, 4 (0.7%) extraction
      unreproducible positive, 6 (1.1%) ELISA unreproducible positive, and 5 (0.9%) non
      conclusive. Upon retesting, the unreproducible positive results turned negative
      except for one which turned non-conclusive. The confirmed positive and non
      conclusive had similar GM-ODIs (p>0.4) upon retesting after storage <=72h at 4 
      degrees C (n = 20) or eight months at -20  degrees C (n = 17). CONCLUSIONS:
      Operational unreproducible positives represent 33% of the GM-positive results and
      a second sample evaluation appears mandatory to avoid useless investigations or
      treatments. When operational artifacts are excluded, GM remains stable at
      standard storage conditions.

PMID- 25860968
TI  - Comprehensive and quantitative analysis of lysophospholipid molecular species
      present in obese mouse liver by shotgun lipidomics.
AB  - Shotgun lipidomics exploits the unique chemical and physical properties of lipid
      classes and individual molecular species to facilitate the high-throughput
      analysis of a cellular lipidome on a large scale directly from the extracts of
      biological samples. A platform for comprehensive analysis of lysophospholipid
      (LPL) species based on shotgun lipidomics has not been established. Herein, after
      extensive characterization of the fragmentation pattern of individual LPL class
      and optimization of all experimental conditions including developing new methods
      for optimization of collision energy, and recovery and enrichment of LPL classes
      from the aqueous phase after solvent extraction, a new method for comprehensive
      and quantitative analysis of LPL species was developed. This newly developed
      method was applied for comprehensive analysis of LPL species present in mouse
      liver samples. Remarkably, the study revealed significant accumulation of LPL
      species in the liver of ob/ob mice. Taken together, by exploiting the principles
      of shotgun lipidomics in combination with a novel strategy of sample preparation,
      LPL species present in biological samples can be determined by the established
      method. We believe that this development is significant and useful for
      understanding the pathways of phospholipid metabolism and for elucidating the
      role of LPL species in signal transduction and other biological functions. 

PMID- 25860969
TI  - Antioxidant, hemolytic, antimicrobial, and cytotoxic activities of the tropical
      Atlantic marine zoanthid Palythoa caribaeorum.
AB  - Marine invertebrates are capable of synthesizing bioactive compounds, which may
      be beneficial to human health. The aim of this study was to evaluate the
      antioxidant, hemolytic, antimicrobial and cytotoxic activities of crude extract
      (70% EtOH), and dichloromethane (DCM), ethyl acetate (EtOAc), and aqueous (Aq)
      fractions of the marine zoanthid Palythoa caribaeorum. The phenolic compound
      contents of the crude extract, DCM, EtOAc and Aq fractions were 12.33, 18.17,
      10.53, and 3.18 mg GAE per gram, respectively. DPPH radical scavenging activity
      showed slight variation. IC50 of crude extract, DCM, EtOAc and Aq fractions were
      11.13, 11.25, 11.74, and 11.28 ug mL(-1), respectively. Among the sample, ferrous
      ion chelating was the highest in crude extract (IC50 302.90 ug mL(-1)), followed
      by EtOAc, Aq, and DCM fractions with 457.77, 547.91, and 641.82 ug mL(-1),
      respectively. Ferric-reducing antioxidant power showed optical density at about
      0.5. The samples tested exhibited low hemolytic activity under 10% up to a
      concentration of 50 MUg mL(-1). No antimicrobial activity was observed against
      any of the tested bacterial strains. For the cytotoxic activity, LC50 of DCM,
      crude extract, EtOAc, and Aq were 52.10, 83.06, 86.34, and 117.45 MUg mL(-1),
      showing high toxicity.

PMID- 25860970
TI  - Short-term low-protein diet during pregnancy alters islet area and protein
      content of phosphatidylinositol 3-kinase pathway in rats.
AB  - The phosphatidylinositol 3-kinase and mitogen-activated protein kinase pathways
      mediate beta cell growth, proliferation, survival and death. We investigated
      whether protein restriction during pregnancy alters islet morphometry or the
      expression and phosphorylation of several proteins involved in the
      phosphatidylinositol 3-kinase and mitogen-activated protein kinase pathways. As
      controls, adult pregnant and non-pregnant rats were fed a normal-protein diet
      (17%). Pregnant and non-pregnant rats in the experimental groups were fed a low
      protein diet (6%) for 15 days. Low protein diet during pregnancy increased serum
      prolactin level, reduced serum corticosterone concentration and the expression of
      both protein kinase B/AKT1 (AKT1) and p70 ribosomal protein S6 kinase (p70S6K),
      as well as the islets area, but did not alter the insulin content of pancreatic
      islets. Pregnancy increased the expression of the Src homology/collagen (SHC)
      protein and the extracellular signal-regulated kinases 1/2 (ERK1/2) independent
      of diet. ERK1/2 phosphorylation (pERK1/2) was similar in islets from pregnant and
      non-pregnant rats fed a low-protein diet, and was higher in islets from pregnant
      rats than in islets from non-pregnant rats fed a normal-protein diet. Thus, a
      short-term, low-protein diet during pregnancy was sufficient to reduce the levels
      of proteins in the phosphatidylinositol 3-kinase pathway and affect islet
      morphometry. 

PMID- 25860971
TI  - Use of dried waste of cassava starch extraction for feeding lactating cows.
AB  - The aim of this study was to determine the best level of utilization of dried
      waste of cassava starch extraction (WCSEd) as a substitute for corn for lactating
      cows. Four lactating cows were fed diets with increasing levels (0%, 33%, 66% and
      100%) of WCSEd as a substitute for corn. The intake and digestibility of dry
      matter and nutrients, milk production and composition, blood parameters of
      glucose and urea and microbial synthesis of the diets were evaluated. There was a
      reduction in dry matter intake, organic matter, ether extract and total
      carbohydrate, and increased intake of acid detergent fiber. Nutrient
      digestibility was not affected while the synthesis of microbial protein
      increased. These changes resulted in reduced milk production, without altering
      the efficiency of production or the constituents of milk, with a decreasing
      effect on daily production of lactose, solids and minerals. Metabolic parameters,
      glucose and urea nitrogen in plasma, remained within appropriate levels. The
      dried residue from the extraction of cassava starch can be used as feed for dairy
      cows to replace up to 100% of the corn ration. However, its use promotes a
      reduction in intake of dry matter and nutrients as well as a reduction in the
      production of milk, with impacts on the profitability of the product. 

PMID- 25860972
TI  - Establishment of research-oriented hospital: an important way for translational
      medicine development in China.
AB  - Globally, one of the major trends is the development of translational medicine.
      The traditional hospital structure could not meet the demands of translational
      medicine development any longer and to explore a novel hospital structure is
      imperative. Following the times, China proposed and implemented a development
      strategy for a first-class modern research-oriented hospital. To establish a
      research-oriented hospital has become an important strategy to guide the
      scientific development of high-quality medical institutions and to advance
      translational medicine development. To facilitate translational medicine by
      developing research-oriented hospital, the Chinese Research Hospital Association
      (CRHA) has been established, which provides service of medicine, talents
      cultivation, scientific research and clinical teaching and covers areas of
      theoretical research, academic exchange, translational medicine, talents training
      and practice guiding. On the whole, research-oriented hospital facilitated
      translational medicine by developing interdisciplinary platform, training core
      competencies in clinical and translational research, providing financial support
      of translational research, and hosting journals on translational medicine, etc. 

PMID- 25860973
TI  - Effect of prey concentrations and feed training on production of Hoplias lacerdae
      juvenile.
AB  - The aim of this work was to investigate the effects of daily prey concentration
      during the first 15 days of active feeding of Hoplias lacerdae larvae, and the
      juvenile size on the feed training. In the first phase, the larvae received five
      Artemia nauplii concentrations (P). In the second phase, the juveniles from each
      treatment were trained to accept formulated diet. Superior growth was related to
      higher initial daily prey concentrations (900 and 1100 nauplii larvae-1). During
      feed training, the growth tendency was similar to that verified in the first
      phase. The lowest values of specific growth rate (SGR) were registered after the
      introduction of the semi-moist diet used in the feed training. However, the
      values of SGR recovered along the experiment and similar rates were found among
      the treatments. Survival, mortality and cannibalism were similar in the different
      treatments at the end of both phases. It can be concluded that: the prey
      concentration affects growth of H. lacerdae during the first 15 days of active
      feeding, and feed training can be initialized with juveniles of about 16 mm of
      total length. 

PMID- 25860975
TI  - Impact of treatment with inhaled corticosteroids on bone mineral density of
      patients with asthma: related with age.
AB  - The effect of inhaled corticosteroid on bone mineral density (BMD) was
      investigated in 44 asthmatic patients after median treatment duration of 6.5
      years. Compared with controls, BMD decreased only in patients aged <50 years in
      both the spine (11.3 %, p = 0.013) and hip (8.8 %, p = 0.044), whereas in
      patients >=50 years BMD did not decrease significantly. INTRODUCTION: The results
      of studies which addressed the impact of inhaled corticosteroid (ICS) therapy on
      BMD of patients with asthma are conflicting. This case-control study aimed to
      compare BMD status in ICS user with asthma with healthy controls according to
      age. METHODS: BMD at the lumbar spine (LS), femoral neck (FN) was measured by
      dual energy X-ray absorptiometry (DEXA). Patients and controls were compared
      according to BMD gr/cm(2), BMD T-score, BMD Z-score, frequency of osteoporosis
      (defined as BMD T-score <=-2.5), and frequency of patients with BMD Z-score <-1
      at LS and FN with regard to age <50 and >=50 years old. RESULTS: Forty-four ICS
      user patients (females 63.6 %) with median treatment duration of 6.5 years and 50
      controls (females, 69.4 %) with respective mean age of 49.2 +/- 9.5 and 47.4 +/-
      10.5 years (p = 0.38 and p = 0.35) entered the study. Overall LS-BMD and FN-BMD
      gr/cm2 in total patients were lower than in controls by 6 % (p = 0.065) and 5.9 %
      (p = 0.09), respectively. In patients <50 years, mean LS-BMD gr/cm(2) was lower
      than controls by 11.3 % (p = 0.013) and FN-BMD by 8.8 % (p = 0.044). Mean BMD T
      score and BMD Z-score in both measurement sites were also lower than controls (p
      = 0.013 and 0.01, respectively. Frequency of osteoporosis did not differ but
      frequency of patients with BMD Z-score <-1 was significantly higher in patients
      (odds ratio (OR) = 6.57 95 % CI, 1.8-23.9, p = 0.004). In age group >=50 years
      old, reduction of BMD in both measurement sites did not reach to a significant
      level. CONCLUSION: This study indicates that BMD reduction in ICS user with
      asthma is dependent on age and appears that younger patients are at greater risk
      of BMD loss. These findings suggest preventive measures particularly in patients
      <50 years.

PMID- 25860976
TI  - Meeting international standards of secondary fracture prevention: a survey on
      Fracture Liaison Services in the Netherlands.
AB  - The Fracture Liaison Service (FLS) is advocated to be effective for the
      prevention of secondary fractures, but implementation is variable. A
      questionnaire based on the International Osteoporosis Foundation (IOF) Capture
      the Fracture(r) FLS standards was used in the current study. The results showed
      high compliancy with the IOF standards in the Dutch responding hospitals.
      INTRODUCTION: The FLS is advocated for the prevention of secondary fractures, but
      its implementation varies between hospitals and countries. The present survey
      applied the standards proposed by the IOF to evaluate the implementation of FLSs
      in non-university hospitals in the Netherlands. METHODS: A questionnaire based on
      the IOF FLS standards was used in this study, requesting the selection,
      evaluation and treatment data of patients older than 50 years with a recent
      fracture. RESULTS: Of 90 invited hospitals, 24 (27 %) fully responded, providing
      data of 24,468 consecutive patients, corresponding with 25 % of fracture patients
      in the Netherlands in the year 2012. After excluding skull and toe fractures and
      patients exceeding the upper age limits applied by individual hospitals, 11,983
      patient data were available for analysis. The data showed high compliance (>90 %)
      for fracture patient identification, invitation for FLS, timing of assessment,
      identification of vertebral fractures, application of national guidelines,
      evaluation of secondary osteoporosis, drug initiation when indicated,
      communication with the general practitioner and application of follow-up strategy
      and 70 % for fall prevention. The response rate was on average (49 %).
      CONCLUSIONS: The available data also showed that patients attending the FLSs were
      evaluated, treated and followed in high compliancy with the IOF standards. Some
      standards are open to different interpretations and may need further
      specification. The major shortcoming in FLS practice was that patients invited to
      attend the FLSs showed a low response rate. None of the hospitals achieved the
      IOF standard patient response rate of over 90 %.

PMID- 25860978
TI  - The relationship between intelligence and training gains is moderated by training
      strategy.
AB  - We examined the relationship between training regimen and fluid intelligence in
      the learning of a complex video game. Fifty non-game-playing young adults were
      trained on a game called Space Fortress for 30 hours with one of two training
      regimens: (1) Hybrid Variable-Priority Training (HVT), with part-task training
      and a focus on improving specific skills and managing task priorities, and (2)
      Full Emphasis Training (FET) in which participants practiced the whole game to
      obtain the highest overall score. Fluid intelligence was measured with the
      Raven's Progressive Matrix task before training. With FET, fluid intelligence was
      positively associated with learning, suggesting that intellectual ability played
      a substantial role in determining individual differences in training success. In
      contrast, with HVT, fluid intelligence was not associated with learning,
      suggesting that individual differences in fluid intelligence do not factor into
      training success in a regimen that emphasizes component tasks and flexible task
      coordination. By analyzing training effects in terms of individual differences
      and training regimens, the current study offers a training approach that
      minimizes the potentially limiting effect of individual differences.

PMID- 25860977
TI  - Relationship between human evolution and neurally mediated syncope disclosed by
      the polymorphic sites of the adrenergic receptor gene alpha2B-AR.
AB  - The objective of this study was to clarify the effects of disease on neurally
      mediated syncope (NMS) during an acute stress reaction. We analyzed the mechanism
      of the molecular interaction and the polymorphisms of the alpha-2 adrenoreceptor
      (alpha2B-AR) gene as the potential psychiatric cause of incentive stress. We
      focused on the following three genotypes of the repeat polymorphism site at Glu
      301-303 in the alpha2B-AR gene: Glu12/12, Glu12/9, and Glu9/9. On the basis of
      our clinical research, NMS is likely to occur in people with the Glu12/9
      heterotype. To verify this, we assessed this relationship with the interaction of
      Gi protein and adenylate cyclase by in silico analysis of the Glu12/9 heterotype.
      By measuring the difference in the dissociation time of the Gi-alpha subunit
      twice, we found that the Glu12/9 heterotype suppressed the action of adenylate
      cyclase longer than the Glu homotypes. As this difference in the Glu repeat
      number effect is thought to be one of the causes of NMS, we investigated the
      evolutionary significance of the Glu repeat number. Glu8 was originally repeated
      in simians, while the Glu12 repeats occurred over time during the evolution of
      bipedalism in humans. Taken with the Glu12 numbers, NMS would likely become a
      defensive measure to prevent significant blood flow to the human brain. 

PMID- 25860979
TI  - Evaluation of Visual Field Progression in Glaucoma: Quasar Regression Program and
      Event Analysis.
AB  - PURPOSE: To determine the sensitivity, specificity and agreement between the
      Quasar program, glaucoma progression analysis (GPA II) event analysis and expert
      opinion in the detection of glaucomatous progression. MATERIALS AND METHODS: The
      Quasar program is based on linear regression analysis of both mean defect (MD)
      and pattern standard deviation (PSD). Each series of visual fields was evaluated
      by three methods; Quasar, GPA II and four experts. The sensitivity, specificity
      and agreement (kappa) for each method was calculated, using expert opinion as the
      reference standard. RESULTS: The study included 439 SITA Standard visual fields
      of 56 eyes of 42 patients, with a mean of 7.8 +/- 0.8 visual fields per eye. When
      suspected cases of progression were considered stable, sensitivity and
      specificity of Quasar, GPA II and the experts were 86.6% and 70.7%, 26.6% and
      95.1%, and 86.6% and 92.6% respectively. When suspected cases of progression were
      considered as progressing, sensitivity and specificity of Quasar, GPA II and the
      experts were 79.1% and 81.2%, 45.8% and 90.6%, and 85.4% and 90.6% respectively.
      The agreement between Quasar and GPA II when suspected cases were considered
      stable or progressing was 0.03 and 0.28 respectively. The degree of agreement
      between Quasar and the experts when suspected cases were considered stable or
      progressing was 0.472 and 0.507. The degree of agreement between GPA II and the
      experts when suspected cases were considered stable or progressing was 0.262 and
      0.342. CONCLUSIONS: The combination of MD and PSD regression analysis in the
      Quasar program showed better agreement with the experts and higher sensitivity
      than GPA II.

PMID- 25860980
TI  - Editorial: Food and Drug Administration Safety Communication on rhBMP-2 use.

PMID- 25860981
TI  - Intraventricular hemorrhage after ventriculoperitoneal shunt revision: a
      retrospective review.
AB  - OBJECT The authors review their ventriculoperitoneal (VP) shunt revisions over a
      3-year period to determine the rate of intraventricular hemorrhage (IVH) and
      subsequent need for re-revision. METHODS Review of medical records identified 35
      pediatric patients who underwent 52 VP shunt revisions between 2009 and 2012. The
      presence and amount of IVH as determined by CT and the time to re-revision were
      documented. The reason for shunting, catheter position, and time between initial
      VP shunt placement and subsequent revisions were also recorded. RESULTS After 13
      (25%) of the 52 revisions, IVH was evident on postoperative CT scans. The
      majority of patients had a trace amount of IVH, with only 2% having IVH greater
      than 5 ml. After 2 (15%) of the 13 revisions associated with IVH, re-revision was
      required within 1 month. In contrast, the re-revision rate in patients without
      IVH was 18%. All of the patients who developed IVH had occipital catheters.
      CONCLUSIONS Some degree of IVH can be expected after approximately one-quarter of
      all VP shunt revision procedures in pediatric patients, but the rate of
      significant IVH is low. Furthermore, the presence of IVH does not necessitate an
      early shunt revision. 

PMID- 25860982
TI  - The efficacy of routine use of recombinant human bone morphogenetic protein-2 in
      occipitocervical and atlantoaxial fusions of the pediatric spine: a minimum of 12
      months' follow-up with computed tomography.
AB  - OBJECT The purpose of this study focusing on fusion rate was to determine the
      efficacy of recombinant human bone morphogenetic protein-2 (rhBMP-2) use in
      posterior instrumented fusions of the craniocervical junction in the pediatric
      population. The authors previously reported the short-term (mean follow-up 11
      months) safety and efficacy of rhBMP-2 use in the pediatric age group. The
      present study reports on their long-term results (minimum of 12 months' follow
      up) and focuses on efficacy. METHODS The authors performed a retrospective review
      of 83 consecutive pediatric patients who had undergone posterior occipitocervical
      or atlantoaxial spine fusion at Texas Children's Hospital or Riley Children's
      Hospital during the period from October 2007 to October 2012. Forty-nine patients
      were excluded from further analysis because of death, loss to follow-up, or lack
      of CT evaluation of fusion at 12 or more months after surgery. Fusion was
      determined by postoperative CT scan at a minimum of 12 months after surgery. The
      fusion was graded and classified by a board-certified fellowship-trained
      pediatric neuroradiologist. Other factors, such as patient age, diagnosis, number
      of vertebral levels fused, use of allograft or autograft, dosage of bone
      morphogenetic protein (BMP), and use of postoperative orthosis, were recorded.
      RESULTS Thirty-four patients had a CT scan at least 12 months after surgery. The
      average age of the patients at surgery was 8 years, 1 month (range 10 months-17
      years). The mean follow-up was 27.7 months (range 12-81 months). There were 37
      fusion procedures in 34 patients. Solid fusion (CT Grade 4 or 4-) was achieved in
      89.2% of attempts (33 of 37), while incomplete fusion or failure of fusion was
      seen in 10.8%. Based on logistic regression analysis, there was no significant
      association between solid fusion and age, sex, BMP dose, type of graft material,
      use of postoperative orthosis, or number of levels fused. Three of 34 patients
      (8.8%) required revision surgery. CONCLUSIONS Despite the large number of adult
      studies reporting positive effects of BMP on bone fusion, our long-term outcomes
      using rhBMP-2 in the pediatric population suggest that rates of fusion failure
      are higher than observed in contemporary adult and pediatric reports of
      occipitocervical and atlantoaxial spine fusions. 

PMID- 25860983
TI  - Superior parietal lobule approach for choroid plexus papillomas without
      preoperative embolization in very young children.
AB  - OBJECT Choroid plexus papillomas (CPPs) are rare neoplasms, often found in the
      atrium of the lateral ventricle of infants, and cause overproduction
      hydrocephalus. The extensive vascularity and medially located blood supply of
      these tumors, coupled with the young age of the patients, can make prevention of
      blood loss challenging. Preoperative embolization has been advocated to reduce
      blood loss and prevent the need for transfusion, but this mandates radiation
      exposure and the additional risks of vessel injury and stroke. For these reasons,
      the authors present their experience using the superior parietal lobule approach
      to CPPs of the atrium without adjunct therapy. METHODS A retrospective review was
      conducted of all children who presented to Columbia University/Morgan Stanley
      Children's Hospital of New York with a CPP in the atrium of the lateral ventricle
      and who underwent surgery using a superior parietal lobule approach without
      preoperative embolization. RESULTS Nine children were included, with a median age
      of 7 months. There were no perioperative complications or new neurological
      deficits. All patients had intraoperative blood loss of less than 100 ml, with a
      mean minimum hematocrit of 26.9% (range 19.6%-36.2%). No patients required a
      blood transfusion. The median follow-up was 39 months, during which time no
      patient demonstrated residual or recurrent tumor on MRI, nor did any have an
      increase in ventricular size or require CSF diversion. CONCLUSIONS The superior
      parietal lobule approach is safe and effective for very young children with CPPs
      in the atrium of the lateral ventricle. The results suggest that preoperative
      embolization is not essential to avoid transfusion or achieve overall good
      outcomes in these patients. This management strategy avoids radiation exposure
      and the additional risks associated with embolization. 

PMID- 25860984
TI  - Routine use of recombinant human bone morphogenetic protein-2 in posterior
      fusions of the pediatric spine and incidence of cancer.
AB  - OBJECT The aim of this study was to determine the safety of recombinant human
      bone morphogenetic protein-2 (rhBMP-2) use in posterior instrumented fusions in
      the pediatric population, focusing on cancer risk. In a previous study, the
      authors reported the short-term (mean follow-up of 11 months) safety and efficacy
      of rhBMP-2 in the pediatric age group. The present study reports their results
      with a minimum of 24 months' follow-up. METHODS The authors retrospectively
      reviewed 57 consecutive cases involving pediatric patients who underwent
      posterior occiptocervical, cervical, thoracic, lumbar, or lumbosacral spine
      fusion from October 1, 2007, to June 30, 2011, at Texas Children's Hospital.
      Seven cases were excluded from further analysis because of loss to follow-up.
      Three patients died during the follow-up period and were placed in a separate
      cohort. RESULTS The patients' average age at the time of surgery was 11 years, 4
      months (range 9 months to 20 years). The mean duration of follow-up was 48.4
      months (range 24-70 months). Cancer status was determined at the most recent
      encounter with the patient and/or caretaker(s) in person, or in telephone follow
      up. Twenty-four or more months after administration of rhBMP-2, there were no
      cases of new malignancy, degeneration, or metastasis of existing tumors. The
      cause of death of the patients who died during the study period was not related
      to BMP or to the development, degeneration, or metastasis of cancer. CONCLUSIONS
      Despite the large number of adult studies reporting increased cancer risk
      associated with BMP use, the authors' outcomes with rhBMP-2 in the pediatric
      population suggest that it is a safe adjunct to posterior spine fusions of the
      occipitocervical, cervical, thoracic, lumbar, and lumbosacral spine. There were
      no new cases of cancer, or degeneration or metastasis of existing malignancies in
      this series. 

PMID- 25860985
TI  - Spring-assisted cranial vault expansion in the setting of multisutural
      craniosynostosis and anomalous venous drainage: case report.
AB  - Patients with multisutural craniosynostosis can develop anomalous venous
      connections between the intracranial sinuses and cutaneous venous system through
      enlarged emissary veins. Cranial vault remodeling in this subset of patients
      carries the risk of massive intraoperative blood loss and/or occlusion of
      collateral draining veins leading to intracranial venous hypertension and raised
      intracranial pressure, increasing the morbidity of cranial expansion. The authors
      report the use of spring-mediated expansion as a technique for cranial
      reconstruction in which the collateral intracranial venous drainage system can be
      preserved. A patient with bilateral lambdoid, sagittal, and unicoronal synostosis
      presented for cranial reconstruction. A tracheostomy and ventriculoperitoneal
      shunt were placed prior to intervention. At the time of reconstruction, a
      Luckenschadel skull abnormality and Chiari malformation Type I were present. A
      preoperative CT venogram demonstrated large collateral superficial occipital
      veins, small bilateral internal jugular veins, and hypoplastic jugular foramina.
      Collateral flow from the transverse and sigmoid sinuses through large occipital
      emissary veins was seen. Spring-mediated cranial vault expansion was performed
      with care to preserve the large collateral veins at the occipital midline. Four
      springs were placed at each lambdoid and the posterior and anterior sagittal
      sutures following 1-cm strip suturectomies. Removal of the springs was performed
      2 months postoperatively. Cranial vault expansion was performed without
      disturbing the aberrant intracranial/extracranial venous collateral system.
      Estimated blood loss was 150 ml. A CT scan obtained 3 months postoperatively
      showed resolution of the Luckenschadel deformity and a 40% volumetric increase in
      the skull compared with the preoperative CT. Patients with anomalous venous
      drainage patterns and multisutural synostosis can undergo spring-mediated cranial
      vault expansion while preserving the major emissary veins draining the
      intracranial sinuses. Risks of blood loss, intracranial venous hypertension, and
      increased intracranial pressure may be decreased compared with traditional
      techniques of repair. 

PMID- 25860986
TI  - Purely endoscopic resection of a choroid plexus papilloma of the third ventricle:
      case report.
AB  - The authors report an illustrative case of a purely endoscopic surgical approach
      to successfully remove a solid choroid plexus papilloma of the third ventricle in
      an infant. A 10-week-old male infant first presented with transient episodes of
      forced downward gaze, divergent macrocephaly, a tense anterior fontanel,
      diastasis of the cranial sutures, and papilledema. Brain MRI revealed a small,
      multilobulated contrast-enhancing mass situated within the posterior third
      ventricle, with resultant obstructive hydrocephalus. A purely endoscopic removal
      of the tumor was performed through a single right frontal bur hole.
      Intraoperatively, a unique vascular tributary was recognized coming from the tela
      choroidea and was controlled with coagulation and sharp dissection. Postoperative
      MRI confirmed complete tumor removal, and the tumor was classified as a choroid
      plexus papilloma. There has been no evidence of tumor recurrence over 42 months
      of follow-up. With this case report the authors intended to show that endoscopic
      surgery can be an additional tool to consider when planning a choroid plexus
      tumor approach. It seems to be of particular interest in selected cases in which
      there are concerns about the patient's total blood volume, as in infants with
      potential hemorrhagic tumors and when it is possible to preoperatively identify a
      single vascular pedicle that can be approached early in the surgery. 

PMID- 25860988
TI  - The Amsterdam Declaration on Essential Surgical Care.

PMID- 25860987
TI  - The impact of covering the bulla with an absorbable polyglycolic acid (PGA) sheet
      during pneumothorax surgery.
AB  - We herein present the pathological findings of a bulla covered using an
      absorbable polyglycolic acid sheet applied with fibrin glue. These findings
      indicated that the membrane of the bulla was reinforced. Covering the bulla with
      an absorbable polyglycolic acid sheet (Neoveil, Gunze Ltd, Kyoto, Japan) and
      applying fibrin glue was effective to prevent the recurrence of the pneumothorax.
      Moreover, this report is the first case report showing the pathological findings
      of a bulla which was covered with an absorbable polyglycolic acid sheet and
      fibrin glue. 

PMID- 25860991
TI  - Correction: Soil bacterial community response to differences in agricultural
      management along with seasonal changes in a Mediterranean region.

PMID- 25860990
TI  - Carbidopa-based modulation of the functional effect of the AAV2-hAADC gene
      therapy in 6-OHDA lesioned rats.
AB  - Progressively blunted response to L-DOPA in Parkinson's disease (PD) is a
      critical factor that complicates long-term pharmacotherapy in view of the central
      importance of this drug in management of the PD-related motor disturbance. This
      phenomenon is likely due to progressive loss of one of the key enzymes involved
      in the biosynthetic pathway for dopamine in the basal ganglia: aromatic L-amino
      acid decarboxylase (AADC). We have developed a gene therapy based on an adeno
      associated virus encoding human AADC (AAV2-hAADC) infused into the Parkinsonian
      striatum. Although no adverse clinical effects of the AAV2-hAADC gene therapy
      have been observed so far, the ability to more precisely regulate transgene
      expression or transgene product activity could be an important long-term safety
      feature. The present study was designed to define pharmacological regulation of
      the functional activity of AAV2-hAADC transgene product by manipulating L-DOPA
      and carbidopa (AADC inhibitor) administration in hemi-parkinsonian rats. Thirty
      days after unilateral striatal infusion of AAV2-hAADC, animals displayed circling
      behavior and acceleration of dopamine metabolism in the lesioned striatum after
      administration of a low dose of L-DOPA (5 mg/kg) co-administered with 1.25 mg/kg
      of carbidopa. This phenomenon was not observed in control AAV2-GFP-treated rats.
      Withdrawal of carbidopa from a daily L-DOPA regimen decreased the peripheral L
      DOPA pool, resulting in almost total loss of L-DOPA-induced behavioral response
      in AAV2-hAADC rats and a significant decline in striatal dopamine turnover. The
      serum L-DOPA level correlated with the magnitude of circling behavior in AAV2
      hAADC rats. Additionally, AADC activity in homogenates of lesioned striata
      transduced by AAV2-AADC was 10-fold higher when compared with AAV2-GFP-treated
      control striata, confirming functional transduction. Our data suggests that the
      pharmacological regulation of circulating L-DOPA might be effective in the
      controlling of function of AAV2-hAADC transgene product in PD gene therapy. 

PMID- 25860992
TI  - Task shifting in primary eye care: how sensitive and specific are common signs
      and symptoms to predict conditions requiring referral to specialist eye
      personnel?
AB  - BACKGROUND: The inclusion of primary eye care (PEC) in the scope of services
      provided by general primary health care (PHC) workers is a 'task shifting'
      strategy to help increase access to eye care in Africa. PEC training, in theory,
      teaches PHC workers to recognize specific symptoms and signs and to treat or
      refer according to these. We tested the sensitivity of these symptoms and signs
      at identifying significant eye pathology. METHODS: Specialized eye care personnel
      in three African countries evaluated specific symptoms and signs, using a torch
      alone, in patients who presented to eye clinics. Following this, they conducted a
      more thorough examination necessary to make a definite diagnosis and manage the
      patient. The sensitivities and specificities of the symptoms and signs for
      identifying eyes with conditions requiring referral or threatening sight were
      calculated. RESULTS: Sensitivities of individual symptoms and signs to detect
      sight threatening pathology ranged from 6.0% to 55.1%; specificities ranged from
      8.6 to 98.9. Using a combination of symptoms or signs increased the sensitivity
      to 80.8 but specificity was 53.2. CONCLUSIONS: In this study, the sensitivity and
      specificity of commonly used symptoms and signs were too low to be useful in
      guiding PHC workers to accurately identify and refer patients with eye
      complaints. This raises the question of whether this task shifting strategy is
      likely to contribute to reducing visual loss or to providing an acceptable
      quality service.

PMID- 25860994
TI  - Correction: Dynamics of Sun5 localization during spermatogenesis in wild type and
      Dpy19l2 knock-out mice indicates that Sun5 is not involved in acrosome attachment
      to the nuclear envelope.

PMID- 25860993
TI  - Dual mechanism of ion permeation through VDAC revealed with inorganic phosphate
      ions and phosphate metabolites.
AB  - In the exchange of metabolites and ions between the mitochondrion and the
      cytosol, the voltage-dependent anion channel (VDAC) is a key element, as it forms
      the major transport pathway for these compounds through the mitochondrial outer
      membrane. Numerous experimental studies have promoted the idea that VDAC acts as
      a regulator of essential mitochondrial functions. In this study, using a
      combination of molecular dynamics simulations, free-energy calculations, and
      electrophysiological measurements, we investigated the transport of ions through
      VDAC, with a focus on phosphate ions and metabolites. We showed that selectivity
      of VDAC towards small anions including monovalent phosphates arises from short
      lived interactions with positively charged residues scattered throughout the
      pore. In dramatic contrast, permeation of divalent phosphate ions and phosphate
      metabolites (AMP and ATP) involves binding sites along a specific translocation
      pathway. This permeation mechanism offers an explanation for the decrease in VDAC
      conductance measured in the presence of ATP or AMP at physiological salt
      concentration. The binding sites occur at similar locations for the divalent
      phosphate ions, AMP and ATP, and contain identical basic residues. ATP features a
      marked affinity for a central region of the pore lined by two lysines and one
      arginine of the N-terminal helix. This cluster of residues together with a few
      other basic amino acids forms a "charged brush" which facilitates the passage of
      the anionic metabolites through the pore. All of this reveals that VDAC controls
      the transport of the inorganic phosphates and phosphate metabolites studied here
      through two different mechanisms. 

PMID- 25860995
TI  - Immunosuppression in early postnatal days induces persistent and allergen
      specific immune tolerance to asthma in adult mice.
AB  - Bronchial asthma is a chronic airway inflammatory condition with high morbidity,
      and effective treatments for asthma are limited. Allergen-specific immunotherapy
      can only induce peripheral immune tolerance and is not sustainable. Exploring new
      therapeutic strategies is of great clinical importance. Recombinant adenovirus
      (rAdV) was used as a vector to make cells expressing cytotoxic T lymphocyte
      associated antigen-4-immunoglobulin (CTLA4Ig) a soluble CTLA4 immunoglobulin
      fusion protein. Dendritic cells (DCs) were modified using the rAdVs together with
      allergens. Then these modified DCs were transplanted to mice before allergen
      sensitization. The persistence and specificity of immune tolerance were evaluated
      in mice challenged with asthma allergens at 3 and 7 months. DCs modified by
      CTLA4Ig showed increased IL-10 secretion, decreased IL-12 secretion, and T cell
      stimulation in vitro. Mice treated with these DCs in the early neonatal period
      developed tolerance against the allergens that were used to induce asthma in the
      adult stage. Asthma symptoms, lung damage, airway reactivity, and inflammatory
      response all improved. Humoral immunity indices showed that this therapeutic
      strategy strongly suppressed mice immune responses and was maintained for as long
      as 7 months. Furthermore, allergen cross-sensitization and challenge experiments
      demonstrated that this immune tolerance was allergen-specific. Treatment with
      CTLA4Ig modified DCs in the early neonatal period, inducing persistent and
      allergen-specific immune tolerance to asthma in adult mice. Our results suggest
      that it may be possible to develop a vaccine for asthma. 

PMID- 25860996
TI  - Differential segmental motion contribution of single- and two-level anterior
      cervical discectomy and fusion.
AB  - PURPOSE: To determine and compare the biomechanical effects of single- and two
      level anterior cervical decompression and fusion (ACDF) on the re-distribution of
      the segmental contribution to total cervical range of motion (ROM) in a
      prospective longitudinal design. METHODS: Fifty-one patients undergoing either a
      single- or two-level ACDF due to cervical disc disease were recruited. Functional
      radiographs were taken preoperatively and then at 3, 6 and 12-month follow-ups.
      Global ROM of C2-C7, ROM of the treated functional spinal unit (FSU) and the
      superior and inferior segmental ROMs were then measured. The relative
      contribution from the FSU and each of the adjacent segments to total cervical ROM
      were compared pre- and post-operatively within and between the two groups at each
      of the time points. RESULTS: Single-level ACDF patients demonstrated a
      significantly greater total cervical ROM at 6 and 12 months compared with the two
      level ACDF group (p = 0.021 and 0.045, respectively). A significantly greater
      contribution from the FSU to the total ROM was found at 3 months in the two-level
      ACDF group (p = 0.016), but the greater contribution shifted to the superior
      adjacent segment at 6 and 12 months (p = 0.025 and 0.046). The two-level ACDF
      group did not demonstrate a significant difference at 3 months (p = 0.087), but a
      significant increase in contribution was found at 6 and 12 months (p < 0.01).
      CONCLUSIONS: Single-level ACDF maintains and restores a more physiological re
      distribution of segmental contribution of ROM compared with two-level ACDF, which
      required longer time to achieve stable FSU immobilization and coupled with
      significantly increased superior segment contribution.

PMID- 25860997
TI  - Solitary sacral osteochondroma without neurological symptoms: a case report and
      review of the literature.
AB  - PURPOSE: To report a case of solitary sacral osteochondroma without neurological
      symptoms and describe the en bloc excision of the tumour, as well as review the
      literature on osteochondroma involving the sacrum. METHODS:  SUMMARY OF THE
      BACKGROUND DATA: although osteochondromas are among the most common benign
      tumours of the bone, they uncommonly involve the spine. Its occurence in the
      sacrum is rare, accounting for only 0.5 % of the osteochondromas involving spine.
      All previous cases of sacral osteochondroma have reported neurological symptoms
      on presentation. CASE REPORT: A 21-year-old male presented with a palpable,
      painless mass in the left side of the sacral region of 1 year duration, without
      neurological symptoms. Radiological studies showed a well-circumscribed lesion
      with bony osteoid within arising from the sacrum at S3-S4 level left to midline,
      with features suggestive of osteochondroma. The tumour was excised en bloc
      through posterior approach. A literature review of sacral osteochondroma was
      conducted using MEDLINE search of English Literature and bibliographies. RESULTS:
      Histopathological studies showed the lesion to consist mature bone trabeculae
      with active enchondral ossification with cap of normal hyaline cartilage.
      Literature review yielded only 8 cases of sacral osteochondroma reported earlier.
      CONCLUSION: This is the 9th case of solitary osteochondroma of the sacrum to be
      reported, the first to be reported without any neurological symptoms, and third
      case reported for which en bloc excision was performed.

PMID- 25860998
TI  - Molecular epidemiology of outbreak-associated pseudorabies virus (PRV) strains in
      central China.
AB  - In several parts of China, there have been a large number of pseudorabies (PR)
      outbreaks which have devastated many swine farms even though the herds had been
      previously immunized with gE-deleted vaccines (Bartha-K61). The emergence of
      these outbreak-associated PRV strains might indicate that Bartha-K61 vaccine
      could not provide effective protection and poses challenges for current serologic
      diagnostics of anti-PRV antibodies. Here, we performed phylogenetic analyses
      based on partial gE, gB, and gC genes to provide information about the molecular
      epidemiology, diagnostics, and immune protection in these outbreak-associated PRV
      strains. Our results indicated that the maximal nucleotide sequence divergence
      for gE, gB, and gC genes are 1.7, 0.4, and 2.7 % within the cluster where
      outbreak-associated PRV strains were located, and are 2.3, 2.7, and 7.6 % with
      other clusters in the phylogenetic trees, respectively. Phylogenetic analyses
      revealed that gE, gB, and gC genes of the twelve outbreak-associated PRV strains
      clustered to a relatively independent branch of the tree, and evolved from the
      same ancestor with strains Ea-China-1999, Fa-China-2001, and BJ-China-2008. The
      genetic relationship between these outbreak-associated PRV strains and strain
      Bartha is not close which may genetically explain the emergence of PR outbreaks
      in Bartha-K61-vaccinated swine farms. We suggest that these outbreak-associated
      PRV strains originate from earlier strains in local regions in China.

PMID- 25860999
TI  - Screening and analysis on the protein interaction of the protein VP7 in grass
      carp reovirus.
AB  - Grass carp reovirus (GCRV) has caused serious economic losses for several decades
      in China. The protein VP7 is one of the important structural proteins in GCRV.
      Recent studies indicated that the protein VP7 had the commendable antigenicity
      and immunogenicity. The protein VP7 cooperated with VP5 could change the
      conformation of the cell membrane and facilitate entry of GCRV into host cells.
      We speculated that the protein VP7 should play an important role in the
      pathogenesis of GCRV. In order to explore the function of the protein VP7, the
      bait protein expression plasmid pGBKT7-vp7 and the cDNA library of CIK cells were
      constructed. By yeast two-hybrid system, after multiple screening with the high
      screening rate medium, rotary verification, sequencing and bioinformatics
      analysis, the interactions of the protein VP7 with ribosomal protein S20 (RPS20)
      and eukaryotic translation initiation factor 3 subunit b (eIF3b) in CIK cells
      were identified. RPS20 played the important roles in the generation of influenza
      B virus and a variety of diseases. eIF3b was relative to the infection of some
      viruses. This study suggested that the protein VP7 played the role in viral
      replication and most likely interacted with host proteins by RPS20 and eIF3b. The
      interaction mechanisms of the protein VP7 with RPS20 and eIF3b, and the
      subsequent effector mechanisms needed to be further studied. The corresponding
      protein interaction of the protein VP7 was not acquired in bioinformatics. The
      protein VP7 and its untranslated region may have the unknown special function.
      This study laid the foundation for deeply exploring the function of the protein
      VP7 in GCRV and had the important scientific significance for exploring the
      pathogenic mechanism of GCRV. 

PMID- 25861002
TI  - Fears, coping and perceived efficacy of coping mechanisms among South African
      children living in children's homes.
AB  - BACKGROUND: The present study examined common childhood fears, coping strategies
      and perceived efficacy of coping mechanisms among 8- to 13-year-old South African
      children (n = 141) living in four children's homes. METHOD: Fears were assessed
      by means of the Fear List Method (FLM) and the Fear Survey Schedule for Children
      Revised (FSSC-R). For both measures, the content and number of fears were
      determined. The FSSC-R was also used to establish the levels of fearfulness, as
      well as the pattern of fears. Coping strategies and the perceived efficacy of
      these strategies were assessed by means of open-ended questions. RESULTS: The
      rank orders of fears as obtained with the FLM were quite different from those
      derived from the FSSC-R. Girls expressed more fears as well as higher levels of
      fears than boys. Secondary coping strategies (i.e. seeking social and/or
      spiritual support) were most often engaged in and were also perceived as most
      effective. CONCLUSIONS: A greater sensitivity to the emotional needs, especially
      with regard to fears, coping and perceived efficacy, of special populations is
      recommended.

PMID- 25861000
TI  - Use of oral bisphosphonates in primary prevention of fractures in postmenopausal
      women: a population-based cohort study.
AB  - OBJECTIVE: To compare incidence of first osteoporotic fracture in two cohorts of
      postmenopausal women, one treated with bisphosphonates and the other only with
      calcium and vitamin D. DESIGN: Retrospective population cohort study with paired
      matching based on data from electronic health records. SETTING: Women aged 60
      years and older in 2005, from 21 primary care centers in a healthcare region of
      Spain. PARTICIPANTS: Two groups of women aged 60 years and older (n = 1208),
      prescribed either calcium and vitamin D (CalVitD) or bisphosphonates (BIPHOS)
      with or without calcium and vitamin D, were compared for the end point of first
      recorded osteoporotic-related fracture, with 5-years follow-up. MAIN OUTCOME
      MEASURE: Incidence of first fracture: Vertebral fracture, osteoporosis with
      pathological fracture, fracture of the upper humeral epiphysis, fracture of the
      lower radial epiphysis, or femur fracture. RESULTS: Estimated 10-year risk of
      fracture was 11.4% (95% confidence interval: 9.6 to 13.2), 11.8% (9.2 to 14.3) in
      the BIPHOS group and 11.1% (8.6 to 13.6) in the CalVitD group. No significant
      differences were found between groups in total fractures (Hazard ratio = 0.934
      (0.67 to 1.31)) or location (vertebral, femoral, radial or humeral). CONCLUSIONS:
      In postmenopausal women, bisphosphonates have not been shown to better decrease
      risk of first fracture compared with calcium and vitamin D therapy alone.

PMID- 25861003
TI  - Maternal depression and anxiety among children with mental health problems.
AB  - OBJECTIVE: The investigation sought to examine depression and anxiety levels in
      mothers of children with mental health problems. METHOD: A case control design
      was employed and self-reports of depressive and anxiety symptoms were measured in
      a group of women whose children were receiving mental health care, as well as a
      community control group and a group of women receiving outpatient psychiatric
      care. RESULTS: No significant differences were noted in depressive and anxiety
      symptoms between the mothers of children with mental health problems and the
      community controls, although both of these groups showed significantly lower
      levels of depression and anxiety than the psychiatric patient group. These
      findings were not influenced by demographic variables Conclusions: The findings
      are contrary to those of high income countries where mothers of children with
      mental health problems show higher levels of depression and anxiety. This
      disparity may be due to the sampling and mental health service usage patterns in
      low-income countries where mothers who seek mental health care for their children
      probably constitute a specific group of people who have awareness of mental
      health problems and available services. As a result their own mental health is
      likely to be better.

PMID- 25861001
TI  - Visualizing KcsA conformational changes upon ion binding by infrared spectroscopy
      and atomistic modeling.
AB  - The effect of ion binding in the selectivity filter of the potassium channel KcsA
      is investigated by combining amide I Fourier-transform infrared spectroscopy with
      structure-based spectral modeling. Experimental difference IR spectra between
      K(+)-bound KcsA and Na(+)-bound KcsA are in good qualitative agreement with
      spectra modeled from structural ensembles generated from molecular dynamics
      simulations. The molecular origins of the vibrational modes contributing to
      differences in these spectra are determined not only from structural differences
      in the selectivity filter but also from the pore helices surrounding this region.
      Furthermore, the coordination of K(+) or Na(+) to carbonyls in the selectivity
      filter effectively decouples the vibrations of those carbonyls from the rest of
      the protein, creating local probes of the electrostatic environment. The results
      suggest that it is necessary to include the influence of the surrounding helices
      in discussing selectivity and transport in KcsA and, on a more general level,
      that IR spectroscopy offers a nonperturbative route to studying the structure and
      dynamics of ion channels. 

PMID- 25861004
TI  - Characteristics of mentoring relationships.
AB  - OBJECTIVE: Mentoring programmes offer an increasingly popular solution to the
      problem of youth 'at-risk'. While positive outcomes of these programmes are
      widely documented, there has been little research into the operant processes. The
      aim of this study was to provide in-depth qualitative information about
      relationship processes in the Big Brothers Big Sisters of South Africa programme.
      METHOD: The sample consisted of mentors and youth in eight relationships. Semi
      structured interviews were conducted with the participants and were analysed
      making use of the narrative method. RESULTS: Relationships were classified into
      two groups, namely those constructed in terms of their purpose to help the
      mentees, and those constructed as friendship for their own sakes. These
      relationships displayed the qualities previously associated with negative and
      positive relationships, respectively. The results of the study further extend
      previous findings, revealing the interaction of these overt qualities with
      underlying constructions of relationships. CONCLUSION: The study highlights the
      influence of the programme and broader social context on the mentoring
      relationships. It indicates the importance of the partners' ability to move
      beyond the constraints of contextually available narratives of their
      relationships, and to establish more personal connections, based on the value of
      the relationship itself, rather than on the programme's ultimate goals.

PMID- 25861005
TI  - The prevalence of anxiety and depression symptoms and syndromes in Kenyan
      children and adolescents.
AB  - BACKGROUND: Community studies on children and adolescents in Western settings
      suggest prevalence rates of anxiety and depressive symptoms that require
      intervention. AIM: To establish equivalent prevalence rates in a Kenyan
      (developing country) situation Method: Self-administered questionnaires for socio
      demographic data, three Diagnostic and Statistical Manual of Mental Disorders -
      Fourth Edition (DSM-IV)-based instruments for anxiety symptoms and syndromes in
      children, one instrument for depression and one culture sensitive instrument for
      depression and anxiety were administered in three different sets to 3 775
      randomly sampled students drawn from a stratified sample of 34.7% of all public
      secondary schools in Nairobi, Kenya. RESULTS: The prevalence rates of anxiety and
      depression symptoms and syndromes varied widely depending on sex and age and also
      on the emphasis of the different instruments used, and also according to the cut
      off points for the various syndromes and instruments. Clinical diagnostic scores
      for depression were recorded in 43.7% of all the students. Using the cut-off
      points for the Multidimensional Anxiety Scale for Children (MASC), anxiety was
      recorded in 12.9% of all students. Nearly half (40.7%) of the respondents who
      completed the Short Leyton Obsessional Inventory for Children and Adolescents had
      positive scores for obsessive disorder, 81.1% were positive for compulsive
      disorder and an average of 69.1% had positive scores for both obsessive and
      compulsive disorders combined. Amongst those who completed the Ndetei-Othieno
      Kathuku (NOK) scale for Depression and Anxiety, 49.3% had positive scores for
      moderate to severe anxiety with or without depression. The Screen for Child
      Anxiety Related Disorders - Revised (SCARED-R) yielded high levels (50-100%) for
      the different syndromes, with obsessive-compulsive disorder at 99.3%, just below
      separation anxiety and school phobia at 100%. Suicidal thoughts and plans were
      prevalent at 4.9-5.5%. CONCLUSION: Anxiety and depression were found at
      prevalence rates no less than is found in the West. This calls for appropriate
      clinical practices and policies.

PMID- 25861006
TI  - Raising a mentally ill son.

PMID- 25861007
TI  - The Tiga programme.

PMID- 25861008
TI  - Containment and reciprocity: integrating psychoanalytic theory and child
      development research for work with children.

PMID- 25861010
TI  - Resilient therapy: working with children and families.

PMID- 25861009
TI  - Treating bulimia in adolescents: a family-based approach.

PMID- 25861011
TI  - Babies in Mind: Understanding Your Baby's Psychological Needs.

PMID- 25861012
TI  - Out-of-pocket costs and other determinants of access to healthcare for children
      with febrile illnesses: a case-control study in rural Tanzania.
AB  - OBJECTIVES: To study private costs and other determinants of access to healthcare
      for childhood fevers in rural Tanzania. METHODS: A case-control study was
      conducted in Tanzania to establish factors that determine access to a health
      facility in acute febrile illnesses in children less than 5 years of age. Carers
      of eligible children were interviewed in the community; cases were represented by
      patients who went to a facility and controls by those who did not. A Household
      Wealth Index was estimated using principal components analysis. A multivariable
      logistic regression analysis was performed to understand the factors which
      influenced attendance of healthcare facility including severity of the illness
      and household wealth/socio-demographic indicators. To complement the data on
      costs from community interviews, a hospital-based study obtained details of
      private expenditures for hospitalised children under the age of 5. RESULTS:
      Severe febrile illness is strongly associated with health facility attendance
      (OR: 35.76, 95%CI: 3.68-347.43, p = 0.002 compared with less severe febrile
      illness). Overall, the private costs of an illness for patients who went to a
      hospital were six times larger than private costs of controls ($5.68 vs. $0.90,
      p<0.0001). Household wealth was not significantly correlated with total costs
      incurred. The separate hospital based cost study indicated that private costs
      were three times greater for admissions at the mission versus public hospital:
      $13.68 mission vs. $4.47 public hospital (difference $ 9.21 (95% CI: 7.89 
      10.52), p<0.0001). In both locations, approximately 50% of the cost was
      determined by the duration of admission, with each day in hospital increasing
      private costs by about 12% (95% CI: 5% - 21%). CONCLUSION: The more severely ill
      a child, the higher the probability of attending hospital. We did not find
      association between household wealth and attending a health facility; nor was
      there an association between household wealth and private cost.

PMID- 25861013
TI  - Exercise type and volume alter signaling pathways regulating skeletal muscle
      glucose uptake and protein synthesis.
AB  - PURPOSE: The aim of this study was to compare activation of cellular signaling
      pathways regulating protein synthesis and glucose uptake in skeletal muscle
      between resistance and endurance exercise. Moreover, the effect of resistance
      exercise volume was examined. METHODS: Three groups of male volunteers (26 +/- 3
      years) were examined: 5 * 10 repetition maximum (RM) resistance exercise (RE)
      with leg press device (5 * 10 RE; n = 8), 10 * 10 RE (n = 11), and endurance
      exercise (strenuous 50-min walking with extra load on a treadmill; EE; n = 8).
      Muscle biopsies were obtained from m.vastus lateralis 30 min pre- and post
      exercise. RESULTS: Downstream markers of mTORC1, p-p70S6K(Thr421/Ser424) and p
      rpS6(Ser240/244), increased more after 10 * 10 RE than after 5 * 10 RE (p < 0.05)
      and EE (p < 0.01-0.001). Exercise-induced changes in p-IRS-I(Ser636/639) that
      inhibit IRS-I signaling via negative feedback from hyperactivated mTORC1
      signaling were greater (p < 0.05) after 10 * 10 RE compared with 5 * 10 RE and
      EE. The changes in energy sensor p-AMPKalpha(Thr172) were greater after 10 * 10
      RE and EE (p < 0.05-0.01) than after 5 * 10 RE. A major regulator of glucose
      uptake in muscle, p-AS160(Thr642), increased more after 10 * 10 RE than after 5 *
      10 RE (p < 0.01) and EE (p < 0.05). CONCLUSION: 10 * 10 RE induced greater
      activation of important signaling proteins regulating glucose uptake (p-AS160)
      and protein synthesis (p-p70S6K, p-rpS6) than 5 * 10 RE and EE. The present
      findings further suggest that, especially after 10 * 10 RE, IRS-I signaling is
      downregulated and that AS160 is activated through AMPK signaling pathway.

PMID- 25861016
TI  - Effect of Eradication of HCV on Hepatic Venous Pressure Gradient in HIV-Infected
      Patients With Compensated HCV-Related Cirrhosis.

PMID- 25861015
TI  - Antiretroviral Drug Use and HIV Drug Resistance Among HIV-Infected Black Men Who
      Have Sex With Men: HIV Prevention Trials Network 061.
AB  - BACKGROUND: HIV Prevention Trials Network (HPTN) 061 enrolled black men who have
      sex with men in the United States. Some men with low/undetectable HIV RNA had
      unusual patterns of antiretroviral (ARV) drug use or had drugs detected in the
      absence of viral suppression. This report includes a comprehensive analysis of
      ARV drug use and drug resistance among men in HPTN 061 who were not virally
      suppressed. METHODS: The analysis included 169 men who had viral loads >400
      copies per milliliter at enrollment, including 3 with acute infection and 13 with
      recent infection. By self-report, 88 were previously diagnosed, including 31 in
      care; 137 men reported no ARV drug use. Samples from these 169 men and 23
      seroconverters were analyzed with HIV genotyping and ARV drug assays. RESULTS:
      Forty-eight (28%) of the 169 men had >= 1 drug resistance mutation (DRM); 19
      (11%) had multiclass resistance. Sixty men (36%) had >= 1 ARV drug detected, 42
      (70%) of whom reported no ARV drug use. Nine (23%) of 39 newly infected men had
      >= 1 DRM; 10 had >= 1 ARV drug detected. Unusual patterns of ARV drugs were
      detected more frequently in newly diagnosed men than previously diagnosed men.
      The rate of transmitted drug resistance was 23% based on HIV genotyping and self
      reported ARV drug use but was 12% after adjusting for ARV drug detection.
      CONCLUSIONS: Many men in HPTN 061 had drug-resistant HIV, and many were at risk
      of acquiring additional DRMs. ARV drug testing revealed unusual patterns of ARV
      drug use and provided a more accurate estimate of transmitted drug resistance.

PMID- 25861017
TI  - Comparisons of musculoskeletal disorders among ten different medical professions
      in Taiwan: a nationwide, population-based study.
AB  - OBJECTIVE: Medical personnel are at risk of musculoskeletal disorders but little
      is known whether the risk of musculoskeletal disorders were different among
      various medical professions. Therefore, this study compared the risk of
      musculoskeletal disorders among personnel of 10 different medical professions in
      Taiwan using a nationwide health claims database. METHODS: Data from the 2000
      2010 Taiwan National Health Insurance Research Database were used to identify
      personnel of 10 different medical professions. Diagnoses based on the
      International Classification of Diseases, Ninth Revision, Clinical Modification
      (ICD-9-CM) were used to identify eight different musculoskeletal disorders that
      occurred after the license issuance date. Cox proportional hazards model was used
      to compare the risk of eight musculoskeletal disorders among the 10 different
      medical professions using dentists as the reference category. RESULTS: A total of
      7,820 medical personnel were included in the analysis. Using dentists as the
      reference category, physical therapists showed a significantly higher risk of all
      eight musculoskeletal disorders (ranging from 1.59 [p = 0.032] in sprains and
      strains of other and unspecified parts of back to 2.93 [p < 0.001] in spondylosis
      and allied disorders). CONCLUSIONS: Compared with dentists, a profession that
      already known to suffer from high rates of work-related musculoskeletal
      disorders, physical therapists, registered nurses, and doctors of Chinese
      medicine showed an even higher risk of musculoskeletal disorders.

PMID- 25861019
TI  - Correction: acal is a long non-coding RNA in JNK signaling in epithelial shape
      changes during drosophila dorsal closure.

PMID- 25861018
TI  - Human normal bronchial epithelial cells: a novel in vitro cell model for toxicity
      evaluation.
AB  - Human normal cell-based systems are needed for drug discovery and toxicity
      evaluation. hTERT or viral genes transduced human cells are currently widely used
      for these studies, while these cells exhibited abnormal differentiation potential
      or response to biological and chemical signals. In this study, we established
      human normal bronchial epithelial cells (HNBEC) using a defined primary
      epithelial cell culture medium without transduction of exogenous genes. This
      system may involve decreased IL-1 signaling and enhanced Wnt signaling in cells.
      Our data demonstrated that HNBEC exhibited a normal diploid karyotype. They
      formed well-defined spheres in matrigel 3D culture while cancer cells (HeLa)
      formed disorganized aggregates. HNBEC cells possessed a normal cellular response
      to DNA damage and did not induce tumor formation in vivo by xenograft assays.
      Importantly, we assessed the potential of these cells in toxicity evaluation of
      the common occupational toxicants that may affect human respiratory system. Our
      results demonstrated that HNBEC cells are more sensitive to exposure of 10~20 nm
      sized SiO2, Cr(VI) and B(a)P compared to 16HBE cells (a SV40-immortalized human
      bronchial epithelial cells). This study provides a novel in vitro human cells
      based model for toxicity evaluation, may also be facilitating studies in basic
      cell biology, cancer biology and drug discovery. 

PMID- 25861020
TI  - Identification of stage-specific biomarkers in lung adenocarcinoma based on RNA
      seq data.
AB  - Tumorigenesis is a multistep process that attributes to the sequential
      accumulation of abnormal expression in key oncogenes or tumor suppressors. We
      aimed to identify stage-specific biomarkers to distinguish lung adenocarcinoma
      (LAC) stages in cancer progression. RNA-sequencing data of LAC and matched
      adjacent non-cancer tissues were downloaded from the Cancer Genome Atlas,
      including 29 pairs of samples from LAC at stage I, 14 from LAC at stage II, 13
      from LAC at stage III, and 1 from LAC at stage IV. Differentially expressed genes
      (DEGs) were analyzed for each case at different stages of LAC. DEGs were further
      annotated based on transcription factor data information, tumor-associated gene
      database, and protein-protein interaction database. Functional annotation was
      performed for genes in PPI network by DAVID online tool. Our analysis identified
      11 high-frequency DEGs in the stage I, 29 in the stage II, and 90 in the stage
      III of LAC. Among them, eight genes were significantly correlated with LAC stages
      and identified as biomarkers in LAC progression. ANGPTL5, C7orf16, EDN3,
      LOC150622, HOXA11AS, IL1F5, and USH1G significantly distinguished stage III from
      stages I and II. GJB6 was significantly enriched in the gap junction trafficking
      pathway, while C7orf16 and EDN3 were enriched in Wnt signaling pathway, cell
      cycle, and G protein-coupled receptor (GPCR) signaling. Up-regulated GJB6
      especially in LAC stage II and down-regulated C7orf16 and EDN3 specifically in
      stage III were identified as biomarkers for distinguishing cancer stage in tumor
      progression through dysregulating gap junction, Wnt signaling, and GPCR signaling
      pathways.

PMID- 25861021
TI  - Interference with the beta-catenin gene in gastric cancer induces changes to the
      miRNA expression profile.
AB  - Aberrant activation of the Wnt/beta-catenin signaling pathway plays a major role
      in carcinogenesis and the progression of many malignant tumors, especially
      gastric cancer (GC). Some research has suggested that expression of the beta
      catenin protein is associated with clinicopathologic factors and affects the
      biological behaviors of GC cells. However, the mechanism of these effects is not
      yet clear. Studies show that the Wnt/beta-catenin pathway regulates some miRNAs.
      We hypothesize that oncogenic activation of beta-catenin signaling is involved in
      the formation of GC through regulating certain microRNAs (miRNAs). The results of
      the current study demonstrate that expression of the beta-catenin protein is
      associated with many clinicopathologic characteristics including the degree of
      differentiation, depth of tumor invasion, tumor site, and 5-year survival rate.
      We found that silencing the expression of beta-catenin with lentiviruses could
      delay cell proliferation, promote apoptosis, weaken the invasive power of GC
      cells, and increase the sensitivity of GC cells to 5-fluorouracil in vitro. Using
      miRNA microarrays to detect changes in the miRNA transcriptome following
      interference with beta-catenin in GC cells, we found that miR-1234-3p, miR-135b
      5p, miR-210, and miR-4739 were commonly upregulated and that miR-20a-3p, miR-23b
      5p, miR-335-3p, miR-423-5p, and miR-455-3p were commonly downregulated. These
      data provide a theoretical basis for the potential interaction between miRNA and
      the beta-catenin signaling pathway in GC.

PMID- 25861022
TI  - Expression and clinical evidence of miR-494 and PTEN in non-small cell lung
      cancer.
AB  - The aim of this study was to explore the expression and clinical significance of
      miR-494 and PTEN (phosphatase and tensin homologue deleted on chromosome ten) in
      non-small cell lung cancer (NSCLC). Immunohistochemistry for PTEN and in situ
      hybridization (ISH) for miR-494 were performed in 92 NSCLC tissues and 10 normal
      lung tissues to detect their expression, and correlation between their expression
      with clinical characteristics and prognosis was analyzed. The expression of miR
      494 was significantly higher in NSCLC than in normal lung tissues (P = 0.004).
      The positive expression of PTEN protein in the lung carcinoma tissues was
      significantly lower than that in the normal lung tissues (P = 0.013), while the
      level of miR-494 expression was negatively correlated with PTEN expression (r = 
      0.577, P < 0.01). The high positive rate of miR-494 was positively correlated
      with pathological TNM (p-TNM) staging and lymph node metastasis. The expression
      of miR-494 was negatively correlated with grade of differentiation. However, the
      expression of PTEN was positively correlated with grade of differentiation.
      Patients with over-expression of miR-494 had a shorter overall survival (OS),
      while the negative group of PTEN was correlated with poor OS. MiR-494 over
      expression and low PTEN expression are closely related to tumor p-TNM staging and
      lymph node metastasis, differentiation, and OS. Combined detection of PTEN and
      miR-494 can aid in determining malignancy degree and the prognosis of patients
      with NSCLC. MiR-494 may be served as a novel prognostic factor and may lead to
      new treatment strategies for NSCLC.

PMID- 25861023
TI  - Microfoci of malignant progression in diffuse low-grade gliomas: towards the
      creation of an intermediate grade in glioma classification?
AB  - Low-grade gliomas (GII) inescapably progress to high-grade gliomas (GIII). The
      duration of this transition is highly variable between patients and reliable
      predictive markers do not exist. We noticed in a subset of cases of GII, obtained
      by awake neurosurgery, the presence of microfoci with high cellular density, high
      vascular density, or minimal endothelial proliferation, which we called GII+. Our
      aim was to investigate whether these foci display immunohistochemical and
      molecular characteristics similar to GIII and whether their presence is
      correlated to poor prognosis. We analyzed cell proliferation, hypoxia,
      vascularization, and alterations of tumorigenic pathways by immunohistochemistry
      (Ki-67, CD31, HIF-1-alpha, EGFR, P-AKT, P53, MDM2) and fluorescence in situ
      hybridization (EGFR, MDM2, PDGFRA) in the hypercellular foci of 16 GII+ cases. We
      compared overall survival between GII, GII+, and GIII. Ki-67, and CD31 expression
      was higher in the foci than in the tumor background in all cases. Aberrant
      expression of protein markers and genomic aberrations were also observed in some
      foci, distinct from the tumor background. Survival was shorter in GII+ than in
      GII cases. Our results suggest that these foci are the early histological
      hallmark of anaplastic transformation, which is supported by molecular
      aberrations. Our study is the first to demonstrate intratumoral morphological,
      immunohistochemical, and molecular heterogeneity in resection specimens of GII,
      the presence of which is correlated to shorter survival. Our findings question
      the discriminative capacity of the current glioma classification and provide
      arguments in favor of the creation of a grade intermediate between GII and GIII,
      to optimize the treatment strategy of GII.

PMID- 25861025
TI  - Automatic detection of diseased tomato plants using thermal and stereo visible
      light images.
AB  - Accurate and timely detection of plant diseases can help mitigate the worldwide
      losses experienced by the horticulture and agriculture industries each year.
      Thermal imaging provides a fast and non-destructive way of scanning plants for
      diseased regions and has been used by various researchers to study the effect of
      disease on the thermal profile of a plant. However, thermal image of a plant
      affected by disease has been known to be affected by environmental conditions
      which include leaf angles and depth of the canopy areas accessible to the thermal
      imaging camera. In this paper, we combine thermal and visible light image data
      with depth information and develop a machine learning system to remotely detect
      plants infected with the tomato powdery mildew fungus Oidium neolycopersici. We
      extract a novel feature set from the image data using local and global statistics
      and show that by combining these with the depth information, we can considerably
      improve the accuracy of detection of the diseased plants. In addition, we show
      that our novel feature set is capable of identifying plants which were not
      originally inoculated with the fungus at the start of the experiment but which
      subsequently developed disease through natural transmission. 

PMID- 25861026
TI  - Ballistic phonon transport in holey silicon.
AB  - When the size of semiconductors is smaller than the phonon mean free path,
      phonons can carry heat with no internal scattering. Ballistic phonon transport
      has received attention for both theoretical and practical aspects because
      Fourier's law of heat conduction breaks down and the heat dissipation in
      nanoscale transistors becomes unpredictable in the ballistic regime. While recent
      experiments demonstrate room-temperature evidence of ballistic phonon transport
      in various nanomaterials, the thermal conductivity data for silicon in the length
      scale of 10-100 nm is still not available due to experimental challenges. Here we
      show ballistic phonon transport prevails in the cross-plane direction of holey
      silicon from 35 to 200 nm. The thermal conductivity scales linearly with the
      length (thickness) even though the lateral dimension (neck) is as narrow as 20
      nm. We assess the impact of long-wavelength phonons and predict a transition from
      ballistic to diffusive regime using scaling models. Our results support strong
      persistence of long-wavelength phonons in nanostructures and are useful for
      controlling phonon transport for thermoelectrics and potential phononic
      applications. 

PMID- 25861024
TI  - Induction of microglia activation after infection with the non-neurotropic
      A/CA/04/2009 H1N1 influenza virus.
AB  - Although influenza is primarily a respiratory disease, it has been shown, in some
      cases, to induce encephalitis, including people acutely infected with the
      pandemic A/California/04/2009 (CA/09) H1N1 virus. Based on previous studies
      showing that the highly pathogenic avian influenza (HPAI) A/Vietnam/1203/2004
      H5N1 virus was neurotropic, induced CNS inflammation and a transient
      parkinsonism, we examined the neurotropic and inflammatory potential of the CA/09
      H1N1 virus in mice. Following intranasal inoculation, we found no evidence for
      CA/09 H1N1 virus neurotropism in the enteric, peripheral or central nervous
      systems. We did, however, observe a robust increase in microglial activity in the
      brain characterized by an increase in the number of activated Iba-1-positive
      microglia in the substantia nigra (SN) and the hippocampus, despite the absence
      of virus in the brain. qPCR analysis in SN tissue showed that the induction of
      microgliosis was preceded by reduced gene expression of the neurotrophic factors
      bdnf, and gdnf and increases in the immune modulatory chemokine chemokine (C-C
      motif) ligand 4 (ccl4). We also noted changes in the expression of transforming
      growth factor-1 (tgfbeta1) in the SN starting at 7 days post-infection (dpi) that
      was sustained through 21 dpi, coupled with increases in arginase-1 (arg1) and
      csf1, M2 markers for microglia. Given that neuroinflammation contributes to
      generation and progression of a number of neurodegenerative disorders, these
      findings have significant implications as they highlight the possibility that
      influenza and perhaps other non-neurotropic viruses can initiate inflammatory
      signals via microglia activation in the brain and contribute to, but not
      necessarily be the primary cause of, neurodegenerative disorders. 

PMID- 25861027
TI  - Real-Time Analysis of Ambient Organic Aerosols Using Aerosol Flowing Atmospheric
      Pressure Afterglow Mass Spectrometry (AeroFAPA-MS).
AB  - Organic compounds contribute to a major fraction of atmospheric aerosols and have
      significant impacts on climate and human health. However, because of their
      chemical complexity, their measurement remains a major challenge for analytical
      instrumentation. Here we present the development and characterization of a new
      soft ionization technique that allows mass spectrometric real-time detection of
      organic compounds in aerosols. The aerosol flowing atmospheric-pressure afterglow
      (AeroFAPA) ion source is based on a helium glow discharge plasma, which generates
      excited helium species and primary reagent ions. Ionization of the analytes
      occurs in the afterglow region after thermal desorption and produces mainly
      intact quasimolecular ions, facilitating the interpretation of the acquired mass
      spectra. We illustrate that changes in aerosol composition and concentration are
      detected on the time scale of seconds and in the ng m(-3) range. Additionally,
      the successful application of AeroFAPA-MS during a field study in a mixed forest
      region is presented. In general, the observed compounds are in agreement with
      previous offline studies; however, the acquisition of chemical information and
      compound identification is much faster. The results demonstrate that AeroFAPA-MS
      is a suitable tool for organic aerosol analysis and reveal the potential of this
      technique to enable new insights into aerosol formation, growth, and
      transformation in the atmosphere. 

PMID- 25861029
TI  - The influence and biomechanical role of cartilage split line pattern on
      tibiofemoral cartilage stress distribution during the stance phase of gait.
AB  - This study presents an evaluation of the role that cartilage fibre 'split line'
      orientation plays in informing femoral cartilage stress patterns. A two-stage
      model is presented consisting of a whole knee joint coupled to a tissue-level
      cartilage model for computational efficiency. The whole joint model may be easily
      customised to any MRI or CT geometry using free-form deformation. Three 'split
      line' patterns (medial-lateral, anterior-posterior and random) were implemented
      in a finite element model with constitutive properties referring to this 'split
      line' orientation as a finite element fibre field. The medial-lateral orientation
      was similar to anatomy and was derived from imaging studies. Model predictions
      showed that 'split lines' are formed along the line of maximum principal strains
      and may have a biomechanical role of protecting the cartilage by limiting the
      cartilage deformation to the area of higher cartilage thickness. 

PMID- 25861028
TI  - A novel approach to enhancing limb control in older adults.
AB  - Two recent experiments have demonstrated that young adult participants were able
      to make faster and more harmonic movements in a typical reciprocal Fitts task (ID
      = 6) following a practice session of sine wave tracking (Boyle et al. in Exp
      Brain Res 223:377-387, 2012; J Mot Behav 46:277-285, 2014). The purpose of the
      present experiment was to replicate these findings with a young adult population
      (age 18-25) and determine whether sine wave tracking also enhances goal-directed
      limb movements in an older adult population (age 65-90). To establish a
      performance baseline, all participants were first pretested on a typical ID = 6
      Fitts task. Participants in each age group were then randomly assigned to one of
      the two training conditions where they practiced (45 trials) on a typical Fitts
      task (ID = 6) or they were asked to track a sine wave template (45 trials).
      Following practice, all participants were then posttested under the ID = 6 Fitts
      conditions. The results demonstrated that both young and older adult participants
      that practiced under the sine wave conditions enhanced their Fitts task
      performance compared to participants in their respective age groups who practiced
      under the Fitts conditions. These enhancements included faster movement times,
      smaller dwell times, and more harmonic movements, all without decreases in
      movement accuracy. These results replicate our previous findings with young
      adults and extend the finding to older adult participants. Interestingly, the
      performances of the older adults following sine wave practice were as fast and as
      accurate as the young adults following Fitts task practice. 

PMID- 25861030
TI  - A Thr72Ala polymorphism in the NKG2D gene is associated with early symptomatic
      congenital cytomegalovirus disease.
AB  - The potential risk factors for congenital cytomegalovirus (cCMV) infection or
      development of disease remain unclear. Here, we investigated the genetic
      polymorphisms in natural killer (NK) group 2, member D (NKG2D), an activating
      receptor expressed on NK cells, and in MHC class I-related chains A, the ligand
      of NKG2D, in 87 cCMV cases, and found that there was a significant association
      between cCMV disease and a single nucleotide polymorphism, Thr72Ala, in NKG2D. 

PMID- 25861031
TI  - Survival after locoregional recurrence or second primary breast cancer: impact of
      the disease-free interval.
AB  - The association between the disease-free interval (DFI) and survival after a
      locoregional recurrence (LRR) or second primary (SP) breast cancer remains
      uncertain. The objective of this study is to clarify this association to obtain
      more information on expected prognosis. Women first diagnosed with early breast
      cancer between 2003-2006 were selected from the Netherlands Cancer Registry. LRRs
      and SP tumours within five years of first diagnosis were examined. The five-year
      period was subsequently divided into three equal intervals. Prognostic
      significance of the DFI on survival after a LRR or SP tumour was determined using
      Kaplan-Meier estimates and multivariable Cox regression analysis. Follow-up was
      complete until January 1, 2014. A total of 37,278 women was included in the
      analysis. LRRs or SP tumours were diagnosed in 890 (2,4%) and 897 (2,4%)
      respectively. Longer DFI was strongly and independently related to an improved
      survival after a LRR (long versus short: HR 0.65, 95% CI 0.48-0.88; medium versus
      short HR 0.81, 95% CI 0.65-1.01). Other factors related to improved survival
      after LRR were younger age (<70 years) and surgical removal of the recurrence. No
      significant association was found between DFI and survival after SP tumours. This
      is the first study to explore the association between the DFI and survival after
      recurrence in a nationwide population-based cancer registry. The DFI before a LRR
      is an independent prognostic factor for survival, with a longer DFI predicting
      better prognosis. 

PMID- 25861032
TI  - Cloning and characterization of three Eimeria tenella lipid phosphate
      phosphatases.
AB  - Although lipid phosphate phosphatases (LPPs) play an important role in cellular
      signaling in addition to lipid biosynthesis, little is thus far known about
      parasite LPPs. In this study, we characterized three Eimeria tenella cDNA clones
      encoding LPP named EtLPP1, EtLPP2 and EtLPP3. Key structural features previously
      described in LPPs, including the three conserved domains proposed as catalytic
      sites, a single conserved N-glycosylation site, and putative transmembrane
      domains were discovered in the three resulting EtLPP amino acid sequences.
      Expression of His6-tagged EtLPP1, -2, and -3 in HEK293 cells produced
      immunoreactive proteins with variable molecular sizes, suggesting the presence of
      multiple forms of each of the three EtLPPs. The two faster-migrating protein
      bands below each of the three EtLPP proteins were found to be very similar to the
      porcine 35-kDa LPP enzyme in their molecular size and the extent of their N
      glycosylation, suggesting that the three EtLPPs are partially N-glycosylated.
      Kinetic analyses of the activity of the three enzymes against PA, LPA, C1P and
      S1P showed that Km values for each of the substrates were (in MUM) 284, 46, 28,
      and 22 for EtLPP1; 369, 179, 237, and 52 for EtLPP2; and 355, 83, and 260 for
      EtLPP3. However, EtLPP3 showed negligible activity on S1P. These results
      confirmed that the three EtLPPs have broad substrate specificity. The results
      also indicated that despite structural similarities, the three EtLPPs may play
      distinct functions through their different models of substrate preference.
      Furthermore, particularly high expression levels of the three EtLPP genes were
      detected in the sporozoite stage of the E. tenella life cycle (p<0.001),
      suggesting that their encoded proteins might play an important biological
      function in the sporozoite stage. 

PMID- 25861033
TI  - Higher body mass index increases the risk for biopsy-mediated detection of
      prostate cancer in Chinese men.
AB  - OBJECTIVE: To investigate the relationship between body mass index (BMI) and
      prostate cancer (PCa) risk at biopsy in Chinese men. PATIENTS AND METHODS: We
      retrospectively reviewed the records of 1,807 consecutive men who underwent
      initial multicore (>=10) prostate biopsy under transrectal ultrasound guidance
      between Dec 2004 and Feb 2014. BMI was categorised based on the Asian
      classification of obesity as follows: <18.5 (underweight), 18.5-22.9 (normal
      weight), 23-24.9 (overweight), 25-29.9 (moderately obese), and >=30 kg/m2
      (severely obese). The odds ratios (OR) of each BMI category for risk of PCa and
      high-grade prostate cancer (HGPCa, Gleason score >=4+3) detection were estimated
      in crude, age-adjusted and multivariate-adjusted models. Prevalence ratios and
      accuracies of PSA predicted PCa were also estimated across BMI groups. RESULTS:
      In total, PCa was detected by biopsy in 750 (45.4%) men, and HGPCa was detected
      in 419 (25.4%) men. Compared with men of normal weight, underweight men and obese
      men were older and had higher prostate specific antigen levels. The risk of
      overall PCa detection via biopsy presented an obvious U-shaped relationship with
      BMI in crude analysis. Overall, 50.0%, 37.4%, 45.6% 54.4% and 74.1% of the men in
      the underweight, normal weight, overweight, moderately obese and severely obese
      groups, respectively, were diagnosed with PCa via biopsy. In multivariate
      analysis, obesity was significantly correlated with a higher risk of PCa
      detection (OR = 1.17, 95%CI 1.10-1.25, P<0.001). However, higher BMI was not
      correlated with HGPCa detection (OR = 1.03, 95%CI 0.97-1.09, P = 0.29). There
      were no significant differences in the accuracy of using PSA to predict PCa or
      HGPCa detection across different BMI categories. CONCLUSION: Obesity was
      associated with higher risk of PCa detection in the present Chinese biopsy
      population. No significant association was detected between obesity and HGPCa.

PMID- 25861034
TI  - Male Gender and Arterial Hypertension are Plaque Predictors at Coronary Computed
      Tomography Angiography.
AB  - BACKGROUND: Systemic Arterial Hypertension (SAH) is one of the main risk factors
      for Coronary Artery Disease (CAD), in addition to male gender. Differences in
      coronary artery lesions between hypertensive and normotensive individuals of both
      genders at the Coronary Computed Tomography Angiography (CCTA) have not been
      clearly determined. OBJECTIVE: To Investigate the calcium score (CS), CAD extent
      and characteristics of coronary plaques at CCTA in men and women with and without
      SAH. METHODS: Prospective cross-sectional study of 509 patients undergoing CCTA
      for CAD diagnosis and risk stratification, from November 2011 to December 2012,
      at Instituto de Cardiologia Dante Pazzanese. Individuals were stratified
      according to gender and subdivided according to the presence (HT +) or absence
      (HT-) of SAH. RESULTS: HT+ women were older (62.3 +/- 10.2 vs 57.8 +/- 12.8, p =
      0.01). As for the assessment of CAD extent, the HT+ individuals of both genders
      had significant CAD, although multivessel disease is more frequent in HT + men.
      The regression analysis for significant CAD showed that age and male gender were
      the determinant factors of multivessel disease and CS >= 100. Plaque type
      analysis showed that SAH was a predictive risk factor for partially calcified
      plaques (OR = 3.9). CONCLUSION: Hypertensive men had multivessel disease more
      often than women. Male gender was a determinant factor of significant CAD,
      multivessel disease, CS >= 100 and calcified and partially calcified plaques,
      whereas SAH was predictive of partially calcified plaques.

PMID- 25861036
TI  - Upper limb evaluation and one-year follow up of non-ambulant patients with spinal
      muscular atrophy: an observational multicenter trial.
AB  - Assessment of the upper limb strength in non-ambulant neuromuscular patients
      remains challenging. Although potential outcome measures have been reported,
      longitudinal data demonstrating sensitivity to clinical evolution in spinal
      muscular atrophy patients are critically lacking. Our study recruited 23 non
      ambulant patients, 16 patients (males/females = 6/10; median age 15.4 years with
      a range from 10.7 to 31.1 years) with spinal muscular atrophy type II and 7
      patients (males/females = 2/5; median age 19.9 years with a range from 8.3 to
      29.9 years) with type III. The Brooke functional score was on median 3 with a
      range from 2 to 6. The average total vital capacity was 46%, and seven patients
      required non-invasive ventilation at night. Patients were assessed at baseline, 6
      months, and 1 year using the Motor Function Measure and innovative devices
      MyoGrip, MyoPinch, and MoviPlate, which assess handgrip strength, key pinch
      strength, and hand/finger extension-flexion function, respectively. The study
      demonstrated the feasibility and reliability of these measures for all patients,
      and sensitivity to negative changes after the age of 14 years. The younger
      patients showed an increase of the distal force in the follow-up period. The
      distal force measurements and function were correlated to different functional
      scales. These data represent an important step in the process of validating these
      devices as potential outcome measures for future clinical trials.

PMID- 25861038
TI  - Femoral supracondylar focal dome osteotomy with plate fixation for acute
      correction of frontal plane knee deformity.
AB  - Focal dome osteotomy (FDO) allows deformity correction without secondary
      translational deformity. The purpose of this study was to evaluate the degree of
      correction and knee functional outcome after correction of frontal knee deformity
      using femoral supracondylar FDO fixed with plate and screws. A prospective study
      included 12 consecutive cases of femoral frontal plane deformity that underwent
      correction using supracondylar focal osteotomy fixed by plate and screws. Average
      age was 27 years, while mean follow-up was 2.1 years. Functional assessment was
      done using the Hospital for Special Surgery (HSS) knee score. The HSS knee score
      improved from 85 to 96.8 points. Desired correction was achieved in all cases.
      Postoperative mechanical axis analysis on long film and scanogram showed no
      secondary deformity. The overall postoperative mechanical axis was at 3.2 mm
      medially (range 2-5 mm). Autogenous bone graft was not used in any case, and
      uneventful osteotomy union was achieved at a mean of 13.8 weeks. Minor
      complications were encountered in two cases. There were no implant failures or
      reoperations. Supracondylar FDO of the femur with plate fixation is a
      reproducible technique that can produce full correction of distal femoral frontal
      plane deformity, while avoiding creating a secondary deformity. Knee function was
      improved with good patient satisfaction. 

PMID- 25861037
TI  - A comparative study of disease genes and drug targets in the human protein
      interactome.
AB  - BACKGROUND: Disease genes cause or contribute genetically to the development of
      the most complex diseases. Drugs are the major approaches to treat the complex
      disease through interacting with their targets. Thus, drug targets are critical
      for treatment efficacy. However, the interrelationship between the disease genes
      and drug targets is not clear. RESULTS: In this study, we comprehensively
      compared the network properties of disease genes and drug targets for five major
      disease categories (cancer, cardiovascular disease, immune system disease,
      metabolic disease, and nervous system disease). We first collected disease genes
      from genome-wide association studies (GWAS) for five disease categories and
      collected their corresponding drugs based on drugs' Anatomical Therapeutic
      Chemical (ATC) classification. Then, we obtained the drug targets for these five
      different disease categories. We found that, though the intersections between
      disease genes and drug targets were small, disease genes were significantly
      enriched in targets compared to their enrichment in human protein-coding genes.
      We further compared network properties of the proteins encoded by disease genes
      and drug targets in human protein-protein interaction networks (interactome). The
      results showed that the drug targets tended to have higher degree, higher
      betweenness, and lower clustering coefficient in cancer Furthermore, we observed
      a clear fraction increase of disease proteins or drug targets in the near
      neighborhood compared with the randomized genes. CONCLUSIONS: The study presents
      the first comprehensive comparison of the disease genes and drug targets in the
      context of interactome. The results provide some foundational network
      characteristics for further designing computational strategies to predict novel
      drug targets and drug repurposing.

PMID- 25861039
TI  - Limb reconstruction in Ollier's disease.
AB  - We present our experience of lengthening and correction of complex deformities in
      the management of patients with Ollier's dysplasia (multiple enchondromatosis)
      from 1985 and 2002. All patients were under 18 years with a minimum follow-up
      time of 2 years (mean 9.6 years, range 2-15 years). There were a total of ten
      patients of which seven were male and three female. The mean age at presentation
      was 10.7 years (range 5-17 years; SD 3.7 years). The total length gain was 42.3
      mm (range 30-110 mm; SD 28.9 mm). The number of days in external fixation was
      164.8 days (range 76-244 days; SD 42.9 days). The bone healing index was 32.5
      days/cm (18-50 days/cm; SD 10.3 days/cm). Patients with Ollier's disease have
      limb length inequality and angular deformities and require multiple
      reconstructive procedures owing to a high incidence of recurrence. We identified
      a tendency for the osteotomy to prematurely consolidate and advise the latency
      period after surgery to be 4-5 days and for distraction to proceed at a faster
      rate. 

PMID- 25861041
TI  - [Mortality risks of migrants: Analysis of the healthy-migrant-effect after the
      2011 German Census].
AB  - In Germany there are 16 million people with a migration background, one in five
      of the total population. There are relatively few migrant mortality studies in
      Germany, which is primarily due to the restricted quantity and quality of
      existing data. The official migrant death statistics for Germany suffer from
      incomplete migrant population stock data due to non-registered remigration
      events. After the German census in 2011 especially the migrant stock data was
      adjusted downwards, and therefore realistic estimates of the migrant mortality
      risk and the healthy-migrant-effect are possible. Between 2010 and 2013 mortality
      risks of foreigners rose strongly due to the census corrections of the migrant
      population. However, the risks for adults and pensioners still lie below the
      risks for Germans in the same age groups. The lower risks indicate a healthy
      migrant-effect, whicht was primarily effective shortly after the immigration
      event. Analysis based on data from the Statutory Pension Insurance (GRV) shows
      higher migrant mortality risks in the age group from 65 to 84. In that age group
      there are supposedly a lot of people, who immigrated to Germany in the context of
      the guest worker recruitment in the 1950s to 1970s and who had hard working
      conditions in their lifetimes. Their mortality risk, therefore, increased in the
      long-term perspective. In the future the lack of data in the migrant population
      will again rise due to unregistered remigration. Alternative databases need to be
      used for migrant mortality analyses. 

PMID- 25861040
TI  - Filamin-a increases the stability and plasma membrane expression of polycystin-2.
AB  - Polycystin-2 (PC2), encoded by the PKD2 gene, is mutated in ~15% of autosomal
      dominant polycystic kidney disease. Filamins are actin-binding proteins
      implicated in scaffolding and membrane stabilization. Here we studied the effects
      of filamin on PC2 stability using filamin-deficient human melanoma M2, filamin-A
      (FLNA)-replete A7, HEK293 and IMCD cells together with FLNA siRNA/shRNA knockdown
      (KD). We found that the presence of FLNA is associated with higher total and
      plasma membrane PC2 protein expression. Western blotting analysis in combination
      with FLNA KD showed that FLNA in A7 cells represses PC2 degradation, prolonging
      the half-life from 2.3 to 4.4 hours. By co-immunoprecipitation and Far Western
      blotting we found that the FLNA C-terminus (FLNAC) reduces the FLNA-PC2 binding
      and PC2 expression, presumably through competing with FLNA for binding PC2. We
      further found that FLNA mediates PC2 binding with actin through forming complex
      PC2-FLNA-actin. FLNAC acted as a blocking peptide and disrupted the link of PC2
      with actin through disrupting the PC2-FLNA-actin complex. Finally, we
      demonstrated that the physical interaction of PC2-FLNA is Ca-dependent. Taken
      together, our current study indicates that FLNA anchors PC2 to the actin
      cytoskeleton through complex PC2-FLNA-actin to reduce degradation and increase
      stability, and possibly regulate PC2 function in a Ca-dependent manner. 

PMID- 25861042
TI  - [Accessibility and quality of rehabilitative services among migrants in Germany].
AB  - BACKGROUND: Migrants comprise a large proportion of the population in Germany. As
      compared to non-migrants they are at a higher risk with respect tor occupational
      accidents, occupational diseases and early retirement due to disability. Tertiary
      preventive services such as rehabilitation, consequently, are of high relevance
      for this population group. OBJECTIVES: We provide an overview of the
      accessibility and quality of preventive services among migrants residing in
      Germany using medical rehabilitation (tertiary prevention) as an example. We also
      present strategies which aim to improve health care for this population group.
      MATERIALS AND METHODS: Summary of quantitative routine data analyses and of
      qualitative interviews with patients and health care professionals in
      rehabilitative care. RESULTS: Migrants utilize rehabilitative health care
      services less often than non-migrants. Those who undergo medical rehabilitation
      report a lower satisfaction with health care and show less favorable health
      outcomes than non-migrants. This, for instance, becomes evident in the
      occupational performance and subjective treatment outcome after rehabilitation.
      Socioeconomic, sociodemographic and health factors only partially explain these
      associations. In addition, there is evidence that migrants face various barriers
      which affect the accessibility and quality of health care services. CONCLUSIONS:
      Health care institutions have to provide services which are more sensitive to the
      heterogeneity of the population in order to reduce barriers in health care.
      Diversity management can contribute to this goal.

PMID- 25861043
TI  - [Strengthening health literacy of people with migration background: results of a
      qualitative evaluation].
AB  - The concept of "health literacy", which has gained attention in English-speaking
      countries during the last decade, is becoming increasingly popular in Germany.
      While studies on an international level indicate that people with migration
      background are often limited in their health literacy, there is a lack of
      empirical data on that topic in Germany. However, it is well known that they are
      exposed to health-related risks and problems comparatively often whereas they use
      health care services less frequently. This article focuses on the native speaking
      counseling services of the Independent Patient Counseling Germany (UPD gGmbH) as
      an example of good practice and introduces the results of the evaluation of this
      counseling service. Qualitative interviews were conducted with UPD-consultants as
      well as with users of the services. It became apparent that Turkish and Russian
      speaking immigrants often have limited health-related literacy. Therefore,
      support and counseling services should focus not only on issues concerning
      language and cultural aspects. Furthermore, strategies strengthening the health
      literacy of persons with migration background are required. Therefore,
      instruments and strategies will be developed in cooperation with the UPD which
      aim to improve such skills of the UPD-consultants. 

PMID- 25861044
TI  - [Prevention among migrants: Participation, migrant sensitive strategies and
      programme characteristics].
AB  - Health promotion and prevention can contribute to a long, healthy life in
      populations both with and without migrant background. This paper provides an
      overview on migrant participation in prevention programmes in Germany.
      Furthermore, we describe migrant sensitive prevention strategies and
      characteristics of prevention programmes for migrants in Germany. With regard to
      participation in prevention programmes, lower vaccination rates are found among
      children and adolescents who migrated to Germany after birth. Among adults with a
      migrant background, we found lower participation in general health check-ups,
      oral health check-ups, cancer screening programs and influenza vaccination.
      Migrant sensitive prevention strategies address the visual style of the material,
      a target group specific risk communication, language requirements, a systematic
      involvement of the target group, and the recognition of deeply rooted
      sociocultural practices and beliefs. On analyzing a large database on prevention
      programs in Germany, we found only a few programmes that were exclusively
      targeted to migrant groups (0.6%). In 16.6% of the programs migrants were
      addressed as the target group among others. Compared to general population
      programs, programs for migrants were more often exclusively directed towards
      girls or women. Moreover, programs for migrants used community-based approaches
      more often and addressed different age groups. Although information on migrant
      participation in prevention programs and utilization of migrant sensitive
      strategies is still incomplete, we can assume that there is a need for diversity
      oriented, migrant sensitive prevention.

PMID- 25861045
TI  - [Not Available].

PMID- 25861046
TI  - Correction: Colorectal adenomas contain multiple somatic mutations that do not
      coincide with synchronous adenocarcinoma specimens.

PMID- 25861049
TI  - Passive sampling for volatile organic compounds in indoor air-controlled
      laboratory comparison of four sampler types.
AB  - This article describes laboratory testing of four passive diffusive samplers for
      assessing indoor air concentrations of volatile organic compounds (VOCs),
      including SKC Ultra II, Radiello(r), Waterloo Membrane Sampler (WMS) and
      Automated Thermal Desorption (ATD) tubes with two different sorbents (Tenax TA
      and Carbopack B). The testing included 10 VOCs (including chlorinated ethenes,
      ethanes, and methanes, aromatic and aliphatic hydrocarbons), spanning a range of
      properties and including some compounds expected to pose challenges (naphthalene,
      methyl ethyl ketone). Tests were conducted at different temperatures (17 to 30 
      degrees C), relative humidities (30 to 90% RH), face velocities (0.014 to 0.41 m
      s(-1)), concentrations (1 to 100 parts per billion by volume [ppbv]) and sampling
      durations (1 to 7 days). The results show that all of the passive samplers
      provided data that met the success criteria (relative percent difference [RPD] <=
      45% of active sample concentrations and coefficient of variation [COV] <= 30%) in
      the majority of cases, but some compounds were problematic for some samplers. The
      passive sampler uptake rates depend to varying degrees on the sampler, sorbent,
      target compounds and environmental conditions, so field calibration is
      advantageous for the highest levels of data quality. 

PMID- 25861047
TI  - Elucidating the influence of gold nanoparticles on the binding of salvianolic
      acid B and rosmarinic acid to bovine serum albumin.
AB  - Salvianolic acid B and rosmarinic acid are two main water-soluble active
      ingredients from Salvia miltiorrhiza with important pharmacological activities
      and clinical applications. The interactions between salvianolic acid B (or
      rosmarinic acid) and bovine serum albumin (BSA) in the presence and absence of
      gold nanoparticles (Au NPs) with three different sizes were investigated by using
      biophysical methods for the first time. Experimental results proved that two
      components quenched the fluorescence of BSA mainly through a static mechanism
      irrespective of the absence or presence of Au NPs. The presence of Au NPs
      decreased the binding constants of salvianolic acid B with BSA from 27.82% to
      10.08%, while Au NPs increased the affinities of rosmarinic acid for BSA from
      0.4% to 14.32%. The conformational change of BSA in the presence of Au NPs
      (caused by a noncompetitive binding between Au NPs and drugs at different albumin
      sites) induced changeable affinity and binding distance between drugs and BSA
      compared with no Au NPs. The competitive experiments revealed that the site I
      (subdomain IIA) of BSA was the primary binding site for salvianolic acid B and
      rosmarinic acid. Additionally, two compounds may induce conformational and micro
      environmental changes of BSA. The results would provide valuable binding
      information between salvianolic acid B (or rosmarinic acid) and BSA, and also
      indicated that the Au NPs could alter the interaction mechanism and binding
      capability of drugs to BSA, which might be beneficial to understanding the
      pharmacokinetics and biological activities of the two drugs. 

PMID- 25861050
TI  - Print and electronic books and journals.

PMID- 25861051
TI  - An Unusual Adrenal Cortical Nodule: Composite Adrenal Cortical Adenoma and
      Adenomatoid Tumor.

PMID- 25861052
TI  - Pre-B Lymphocyte Protein 3 (VPREB3) Expression in the Adrenal Cortex: Precedent
      for non-Immunological Roles in Normal and Neoplastic Human Tissues.
AB  - The pre-B lymphocyte protein 3 (VPREB3) is expressed during B cell
      differentiation and in subsets of mature B lymphocytes and is mainly found in
      bone marrow and lymphoid tissue germinative centers. So far, its function in B
      cells remains to be clarified. The messenger RNA (mRNA) of VPREB3 was previously
      detected in aldosterone-producing adenomas (APA); however, further information
      about this protein in human adrenocortical cells and tissues is currently
      unavailable. Therefore, in the present study, we, for the first time, investigate
      the protein expression of VPREB3 in human adrenocortical tissues. In addition, we
      approach the previously suggested similarities in expression patterns of
      aldosterone-producing cells and Purkinje neurons. Immunohistochemical analysis of
      VPREB3 was performed in 13 nonpathological adrenals (NA), 6 adrenal glands with
      idiopathic hyperaldosteronism (IHA), 18 APA, 5 cortisol-producing adenomas (CPA),
      and 5 nonpathological human cerebellum specimens. The mRNA levels of VPREB3,
      steroidogenic enzymes, and other aldosterone biosynthesis markers were detected
      in 53 APA samples using real-time RT-PCR (qPCR) and compared to the clinical data
      of APA patients. In our results, the VPREB3 protein was diffusely detected in
      APA, partially or weakly detected in CPA, and immunolocalized in the zona
      glomerulosa of NA and IHA, as well as in the cytoplasm of cerebellar Purkinje
      cells. In APA, VPREB3 mRNA levels were significantly correlated to plasma
      aldosterone (P = 0.026; R = 0.30), KCNJ5 mutations (P = 0.0061; mutated 34:19
      wild type), CYP11B2 (P < 0.0001; R = 0.65), Purkinje cell protein 4 (PCP4; P <
      0.0001; R = 0.53), and voltage-dependent calcium channels CaV1.3 (P = 0.023; R =
      0.31) and CaV3.2 (P = 0.0019; R = 0.42). Based on our data, we hypothesize a
      possible role for VPREB3 in aldosterone biosynthesis, and present ideas for
      future functional studies. 

PMID- 25861053
TI  - Basic study for ultrasound-based navigation for pedicle screw insertion using
      transmission and backscattered methods.
AB  - The purpose of this study was to understand the acoustic properties of human
      vertebral cancellous bone and to study the feasibility of ultrasound-based
      navigation for posterior pedicle screw fixation in spinal fusion surgery.
      Fourteen human vertebral specimens were disarticulated from seven un-embalmed
      cadavers (four males, three females, 73.14 +/- 9.87 years, two specimens from
      each cadaver). Seven specimens were used to measure the transmission, including
      tests of attenuation and phase velocity, while the other seven specimens were
      used for backscattered measurements to inspect the depth of penetration and A
      Mode signals. Five pairs of unfocused broadband ultrasonic transducers were used
      for the detection, with center frequencies of 0.5 MHz, 1 MHz, 1.5 MHz, 2.25 MHz,
      and 3.5 MHz. As a result, good and stable results were documented. With increased
      frequency, the attenuation increased (P<0.05), stability of the speed of sound
      improved (P<0.05), and penetration distance decreased (P>0.05). At about 0.6 cm
      away from the cortical bone, warning signals were easily observed from the
      backscattered measurements. In conclusion, the ultrasonic system proved to be an
      effective, moveable, and real-time imaging navigation system. However, how
      ultrasonic navigation will benefit pedicle screw insertion in spinal surgery
      needs to be determined. Therefore, ultrasound-guided pedicle screw implantation
      is theoretically effective and promising. 

PMID- 25861054
TI  - Numerical optimization of alignment reproducibility for customizable surgical
      guides.
AB  - PURPOSE: Computer-assisted orthopedic surgery aims at minimizing invasiveness,
      postoperative pain, and morbidity with computer-assisted preoperative planning
      and intra-operative guidance techniques, of which camera-based navigation and
      patient-specific templates (PST) are the most common. PSTs are one-time templates
      that guide the surgeon initially in cutting slits or drilling holes. This method
      can be extended to reusable and customizable surgical guides (CSG), which can be
      adapted to the patients' bone. Determining the right set of CSG input parameters
      by hand is a challenging task, given the vast amount of input parameter
      combinations and the complex physical interaction between the PST/CSG and the
      bone. METHODS: This paper introduces a novel algorithm to solve the problem of
      choosing the right set of input parameters. Our approach predicts how well a CSG
      instance is able to reproduce the planned alignment based on a physical
      simulation and uses a genetic optimization algorithm to determine optimal
      configurations. We validate our technique with a prototype of a pin-based CSG and
      nine rapid prototyped distal femora. RESULTS: The proposed optimization technique
      has been compared to manual optimization by experts, as well as participants with
      domain experience. Using the optimization technique, the alignment errors
      remained within practical boundaries of 1.2 mm translation and [Formula: see
      text] rotation error. In all cases, the proposed method outperformed manual
      optimization. CONCLUSIONS: Manually optimizing CSG parameters turns out to be a
      counterintuitive task. Even after training, subjects with and without anatomical
      background fail in choosing appropriate CSG configurations. Our optimization
      algorithm ensures that the CSG is configured correctly, and we could demonstrate
      that the intended alignment of the CSG is accurately reproduced on all tested
      bone geometries.

PMID- 25861055
TI  - CranialCloud: a cloud-based architecture to support trans-institutional
      collaborative efforts in neurodegenerative disorders.
AB  - PURPOSE: Neurological diseases have a devastating impact on millions of
      individuals and their families. These diseases will continue to constitute a
      significant research focus for this century. The search for effective treatments
      and cures requires multiple teams of experts in clinical neurosciences,
      neuroradiology, engineering, and industry. Hence, the need to communicate a large
      amount of information with accuracy and precision is more necessary than ever for
      this specialty. METHODS: In this paper, we present a distributed system that
      supports this vision, which we call the CranialVault Cloud (CranialCloud). It
      consists in a network of nodes, each with the capability to store and process
      data, that share the same spatial normalization processes, thus guaranteeing a
      common reference space. We detail and justify design choices, the architecture
      and functionality of individual nodes, the way these nodes interact, and how the
      distributed system can be used to support inter-institutional research. RESULTS:
      We discuss the current state of the system that gathers data for more than 1,600
      patients and how we envision it to grow. CONCLUSION: We contend that the fastest
      way to find and develop promising treatments and cures is to permit teams of
      researchers to aggregate data, spatially normalize these data, and share them.
      The CranialVault system is a system that supports this vision.

PMID- 25861056
TI  - 3D transcranial ultrasound as a novel intra-operative imaging technique for DBS
      surgery: a feasibility study.
AB  - PURPOSE: Intra-operative image guidance during deep brain stimulation (DBS)
      surgery is usually avoided due to cost and overhead of intra-operative MRI and CT
      acquisitions. Recently, there has been interest in the community towards the
      usage of non-invasive transcranial ultrasound (TCUS) through the preauricular
      bone window. In this work, we investigate, for the first time, the feasibility of
      using 3D-TCUS for imaging of already implanted DBS electrodes. As a first step
      towards this goal, we report imaging methods and electrode localisation errors
      outside of the operating room on eight previously operated DBS patients. METHODS:
      We evaluate the feasibility of using 3D-TCUS by registering volumes to pre
      operative T1-MRI. US-MRI registration is achieved through a two-step point-based
      approach. First, a rough surface scan of the subjects' skin surface in 3D-TCUS
      space is registered to a segmented skin-surface point cloud from MRI. Next, we
      perform a refinement using rigid registration of multiple pairs of manually
      marked anatomical landmarks. We validate against post-operative CT scans which
      are also registered to pre-operative MRI. RESULTS: Qualitative results are given
      in form of 3D reconstruction examples at 2.5 and 3.5 MHz TCUS image frequency,
      overlaid on pre-operative T1-MRI and post-operative CT. Quantitative evaluation
      is performed by reporting the accuracy of electrode tip localisation at 2.5 and
      3.5 MHz after our US-MRI approach. As a baseline, we also report RMSE errors for
      pairs of anatomical landmarks in pre-operative MRI and 3D-TCUS. CONCLUSION:
      Multiple image examples show the appearance and quality of 3D-TCUS scans,
      depending on the bone window. Overall accuracy of anatomic point pairs lies on
      the order of 3.2 mm, using our registration approach. Compared to this baseline,
      electrode tip localisation in 3D-TCUS has a mean accuracy on the order of 4.8 mm
      and a precision on the order of 2.3 mm. While insufficient at first glance, we
      argue why these results are promising nonetheless. Our work motivates further
      future work in improved TCUS scanning, advanced TCUS-MRI registration and
      computer-aided electrode detection in 3D-TCUS.

PMID- 25861057
TI  - Induced sporicidal activity of chlorhexidine against Clostridium difficile spores
      under altered physical and chemical conditions.
AB  - BACKGROUND: Chlorhexidine is a broad-spectrum antimicrobial commonly used to
      disinfect the skin of patients to reduce the risk of healthcare-associated
      infections. Because chlorhexidine is not sporicidal, it is not anticipated that
      it would have an impact on skin contamination with Clostridium difficile, the
      most important cause of healthcare-associated diarrhea. However, although
      chlorhexidine is not sporicidal as it is used in healthcare settings, it has been
      reported to kill spores of Bacillus species under altered physical and chemical
      conditions that disrupt the spore's protective barriers (e.g., heat,
      ultrasonication, alcohol, or elevated pH). Here, we tested the hypothesis that
      similarly altered physical and chemical conditions result in enhanced sporicidal
      activity of chlorhexidine against C. difficile spores. PRINCIPAL FINDINGS: C.
      difficile spores became susceptible to heat killing at 80  degrees C within 15
      minutes in the presence of chlorhexidine, as opposed to spores suspended in water
      which remained viable. The extent to which the spores were reduced was directly
      proportional to the concentration of chlorhexidine in solution, with no viable
      spores recovered after 15 minutes of incubation in 0.04%-0.0004% w/v
      chlorhexidine solutions at 80  degrees C. Reduction of spores exposed to 4% w/v
      chlorhexidine solutions at moderate temperatures (37  degrees C and 55  degrees
      C) was enhanced by the presence of 70% ethanol. However, complete elimination of
      spores was not achieved until 3 hours of incubation at 55  degrees C. Elevating
      the pH to >=9.5 significantly enhanced the killing of spores in either aqueous or
      alcoholic chlorhexidine solutions. CONCLUSIONS: Physical and chemical conditions
      that alter the protective barriers of C. difficile spores convey sporicidal
      activity to chlorhexidine. Further studies are necessary to identify additional
      agents that may allow chlorhexidine to reach its target within the spore.

PMID- 25861058
TI  - CBCD: 25 years later!

PMID- 25861059
TI  - Prognostic factors of surgically-treated patients with cancer of the right colon:
      a ten years' experience of a single universitary institution.
AB  - BACKGROUND: Colorectal cancer is one of the most common malignancies in the
      world. There are many controversies in the literature about the prognostic value
      of primary tumor location. Many studies have shown higher survival rates for
      tumors in the right colon, and worse prognosis for lesions located more distally
      in the colon. AIM: To analyze the results of surgical treatment of right-sided
      colon cancers patients operated in one decade period and identify the prognostic
      factors that were associated with lower overall survival in stages I-IV patients.
      METHODS: A retrospective review from the prospectively collected database
      identified 178 patients with right-sided colon cancer surgically treated with
      curative intent. Demographic factors (gender and age), tumor factors (site, T
      stage, N stage, M stage, histological type and tumor differentiation), and lymph
      node yield were extracted to identify those associated with lower overall
      survival. RESULTS: Mean age was 65 (+/- 12) years old, and 105 (56.1%) patients
      were female. Most common affected site was ascending colon (48.1%), followed by
      cecum (41.7%) and hepatic flexure (10.2%). Mean length of hospital stay was 14
      (+/- 2.8) days. T stage distribution was T1 (4.8%), T2 (7.5%), T3 (74.9%), and T4
      (12.8%). Nodal involvement was present in 46.0%, and metastatic disease in 3.7%.
      Twelve or more lymph nodes were obtained in 87.2% of surgical specimens and 84.5%
      were non-mucinous tumors. Mean survival time was 38.3 (+/- 30.8) months. Overall
      survival was affected by T stage, N stage, M stage, and final stage. Lymph node
      involvement (OR=2.06) and stage III/IV (OR=2.81) were independent negative
      prognostic factors. CONCLUSION: Right-sided colon cancer presented commonly at
      advanced stage. Advanced stage and lymph node involvement were factors associated
      with poor long term survival.

PMID- 25861060
TI  - In-hospital weight loss, prescribed diet and food acceptance.
AB  - BACKGROUND: Weight loss and malnutrition may be caused by many factors, including
      type of disease and treatment. AIM: The present study investigated the occurrence
      of in-hospital weight loss and related factors. METHOD: This cross-sectional
      study investigated the following variables of 456 hospitalized patients: gender,
      age, disease, weight variation during hospital stay, and type and acceptance of
      the prescribed diet. Repeated measures analysis of variance (ANOVA) was used for
      comparing patients' weight in the first three days in hospital stay and
      determining which factors affect weight. The generalized estimating equation was
      used for comparing the food acceptance rates. The significance level was set at
      5%. RESULTS: The most prescribed diet was the regular (28.8%) and 45.5% of the
      patients lost weight during their stay. Acceptance of hospital food increased
      from the first to the third days of stay (p=0.0022) but weight loss was still
      significant (p<0.0001). Age and type of prescribed diet did not affect weight
      loss during the study period but type of disease and gender did. Patients with
      neoplasms (p=0.0052) and males (p=0.0002) lost more weight. CONCLUSION: Weight
      loss during hospital stay was associated only with gender and type of disease.

PMID- 25861061
TI  - Influence of surgical technique in the peritoneal carcinomatosis surgical wound
      implant: experimental model in mice.
AB  - BACKGROUND: The number of malignancies increased alarmingly. Surgery constitutes
      one of the most efficient therapeutic modalities for the treatment of solid
      tumors. The neoplastic implant in surgical wound is a complication whose
      percentage of occurrence reported in the literature is variable, but sets with
      high morbidity and therapeutic difficulties. Protecting the wound is one of the
      recommended principles of oncologic surgery. AIM: To evaluate the influence of
      wound protection in the development of tumor implantation. METHODS: Sarcoma 180
      tumor cells were used, with intraperitoneal inoculation in Swiss mice. After the
      establishment of neoplastic ascites, animals were randomized into two groups of
      10, each group consisting of five males and five females. In both groups,
      laparotomy and manipulation of intra-abdominal organs was performed. In a group
      laparotomy was performed using the protection of the abdominal wound and the
      other group without it. On the 9th postoperative day macroscopic evaluation of
      the operative scar was performed, which was later removed for microscopic
      evaluation. RESULTS: There was microscopic infiltration of tumor cells in the
      wound of all animals. However, the group that held the protection, infiltration
      was less intense when compared to the group without it. The infiltration was also
      more severe in females than in males of the same group. CONCLUSION: Tumor
      infiltration into the wound was more intense in the group in which the protection
      of the surgical site was not performed, and in females when compared to males of
      the same group.

PMID- 25861062
TI  - Surgical management of cystic dilatation bile ducts in adults.
AB  - BACKGROUND: The cystic dilatation of the biliary tract is a rare disease and
      uncertain origin. It is recognized more frequently in children; however, its
      incidence comes increasing in adults, representing 20% of the cases. AIM: To
      evaluate morbimortality rates, evolution and handing of patients with cystic
      dilatation bile ducts in adults. METHODS: Were evaluated, retrospectively, five
      adults who had the diagnosis of choledochal cyst and that had been submitted to
      some surgical procedure. RESULTS: Abdominal pain was the commonest complain to
      all patients. Jaundice was present in 80%. Ultrasound scanning was done in all
      the cases as initial examination. CT scan, magnetic resonance imaging and
      endoscopic retrograde cholangiopancreatography were also done in some patients;
      however, the diagnosis was established intra-operatively in all cases. The cyst
      resection with reconstruction of the biliary tract was done in 60%; the
      cystojejunostomy in 20%; and in 20% biliary tract drainage. CONCLUSIONS: Biliary
      tract cystic dilatation is a rare disease. However, its incidence is increasing
      in the adult population, so, it must be thought as differential diagnosis when
      facing obstructive jaundice.

PMID- 25861063
TI  - Minimal endoscopic changes in non-erosive reflux disease.
AB  - BACKGROUND: Gastroesophageal reflux disease is an increasingly common condition
      worldwide causing a considerable economic impact. More than half the patients
      with clinical symptoms of reflux disease display no mucosal erosions on
      esophagogastroduodenoscopy, making it impossible to confirm the diagnosis without
      further investigations. AIM: To evaluate the correlation between minimal
      endoscopic changes on white-light esophagogastroduodenoscopy (carditis, mucosal
      thickening and invisibility of vessels) and histologic changes observed in distal
      esophageal biopsies in a sample of patients with symptoms suggestive of reflux
      disease, and to verify the specificity of these symptoms for non-erosive reflux
      disease. METHODS: Retrospective, cross-sectional study based on information
      retrieved from a digital database at a Brazilian hospital for the period March
      October, 2012. The sample consisted of previously untreated, non-smoking subjects
      aged >18 years with symptoms suggestive of reflux disease but no esophageal
      erosions, submitted to esophagogastroduodenoscopy and distal esophageal biopsy.
      RESULTS: The final sample included 23 subjects. The most frequently observed
      change was invisibility of vessels (n=21; 91.3%), followed by mucosal thickening
      (n=15; 65.2%) and carditis (n=5; 21.7%). The correlation coefficient between each
      variable and the anatomopathological diagnosis was 0.386 for body mass index,
      0.479 for mucosal thickening, -0.116 for invisibility of vessels, 0.306 for
      carditis and 0.462 for hiatal hernia. CONCLUSION: All patients displayed minimal
      endoscopic changes on esophagogastroduodenoscopy, but only mucosal thickening
      revealed a moderately significant correlation with severity of esophagitis,
      although increased body mass index values and the presence of hiatal hernia were
      also associated.

PMID- 25861064
TI  - Clinical and therapeutic correlations in patients with slight acute pancreatitis.
AB  - BACKGROUND: Acute pancreatitis is an inflammatory disease of the pancreas due to
      enzymatic autodigestion which can cause necrosis or multiple organ failure; its
      pathophysiology is not fully known yet. AIM: To evaluate the correlation between
      clinical and therapeutic data in patients with mild acute pancreatitis. METHODS:
      A retrospective study in 55 medical records of patients admitted with acute mild
      pancreatitis was realized to analyze the association between age, leukocytosis,
      serum glutamic-oxaloacetic transaminase and lactate dehydrogenase, glucose,
      antibiotics, time admission and Ranson's scores. RESULTS: There was a positive
      association between less intensive care (strict hydration, analgesia and
      monitoring of vital signs), early antibiotic therapy (monotherapy), early return
      to diet after 48 hours and laboratory control of the serum amylase and lipase
      (high in the first week and decreasing after 10 days, without any prognostic
      value). CONCLUSIONS: Changes in the management of patients with mild acute
      pancreatitis, such as enteral nutrition, rational use of lower spectrum
      antibiotics and intensive care, have contributed significantly to the reduction
      of hospitalization time and mortality.

PMID- 25861065
TI  - Esophageal mucosal resection versus esophagectomy: a comparative study of
      surgical results in patients with advanced megaesophagus.
AB  - BACKGROUND: The surgical treatment of advanced megaesophagus has no consensus,
      being esophagectomy the more commonly used method. Since it has high
      morbimortality--inconvenient for benign disease -, in recent years an alternative
      has been introduced: the esophageal mucosal resection. AIM: To compare early and
      late results of the two techniques evaluating the operative time, length of ICU
      stay; postoperative hospitalization; total hospitalization; intra- and
      postoperative complication rates; mortality; and long-term results. METHODS: Were
      evaluated retrospectively 40 charts, 23 esophagectomies and 17 mucosectomies. In
      assessing postoperative results, interviews were conducted by using a specific
      questionnaire. RESULTS: Comparing the means of esophagectomy and mucosal
      resection, respectively, the data were: 1) surgical time--310.2 min and 279.7 min
      (p > 0.05); 2) length of stay in ICU--5 days and 2.53 days (p <0.05); 3) total
      time of hospitalization--24.25 days and 20.76 days (p> 0.05); 4) length of
      hospital stay after surgery--19.05 days and 14.94 days (p> 0.05); 5) presence of
      intraoperative complications--65% and 18% (p <0.05); 6) the presence of
      postoperative complications - 65% and 35% (p> 0.05). In the assessment of late
      postoperative score (range 0-10) esophagectomy (n = 5) obtained 8.8 points and
      8.8 points also got mucosal resection (n = 5). CONCLUSIONS: Esophageal mucosal
      resection proved to be good alternative for surgical treatment of megaesophagus.
      It was advantageous in the immediate postoperative period by presenting a lower
      average time in operation, the total hospitalization, ICU staying and
      complications rate. In the late postoperative period, the result was excellent
      and good in both operations.

PMID- 25861066
TI  - Clinical, endoscopic and manometric features of the primary motor disorders of
      the esophagus.
AB  - BACKGROUND: Significant incidence, diagnostic difficulties, clinical relevance
      and therapeutic efficacy associated with the small number of publications on the
      primary esophageal motor disorders, motivated the present study. AIM: To
      determine the manometric prevalence of these disorders and correlate them to the
      endoscopic and clinical findings. METHODS: A retrospective study of 2614
      patients, being 1529 (58.49%) women and 1085 (41.51%) men. From 299 manometric
      examinations diagnosed with primary esophageal motor disorder, were sought
      clinical data (heartburn, regurgitation, dysphagia, odynophagia, non-cardiac
      chest pain, pharyngeal globe and extra-esophageal symptoms) and/or endoscopic
      (hiatal hernia, erosive esophagitis, food waste) that motivated the performance
      of manometry. RESULTS: Were found 49 cases of achalasia, 73 diffuse spasm, 89
      nutcracker esophagus, 82 ineffective esophageal motility, and six lower
      esophageal sphincter hypertension. In relation to the correlations, it was
      observed that in 119 patients clinical conditions were associated with dysphagia,
      found in achalasia more than in other conditions; in relationship between
      endoscopic findings and clinical conditions there was no statistical significance
      between data. CONCLUSION: The clinical and endoscopic findings have little value
      in the characterization of the primary motor disorders of the esophagus, showing
      even more the need for manometry, particularly in the preoperative period of
      gastroesophageal reflux disease.

PMID- 25861067
TI  - Food intolerances and associated symptoms in patients undergoing Fobi-Capella
      technique without gastric ring.
AB  - BACKGROUND: Bariatric surgery is considered the only effective method to treat
      refractory obesity, and especially for those in which clinical treatment was not
      successful. However, the appearance of food intolerances and clinical
      manifestations are quite common. AIM: To identify food intolerances and
      associated them to symptoms in patients undergoing Fobi-Capella technique without
      gastric ring. METHODS: This was a cross-sectional study of adult patients who had
      more than one year after surgery. Demographic, anthropometric, weight and
      preoperative height data were investigated. Nutritional status was classified
      according to the criteria established by the World Health Organization. It was
      considered food intolerance the presence of nausea, vomiting, diarrhea or
      bloating after eating a particular food. RESULTS: The sample consisted of 61
      patients who attended the nutritional consultation of which 26 (42.6%) had food
      intolerance, mostly related to red meat (n=12; 34.3%) during the first six months
      of operation; there was a significant difference between the periods between 0
      and 6 months, and 7 to 12 (p=0.02). Among the symptoms reported by patients,
      nausea was the most recurrent until the 6th month, but without significant
      differences between the two periods (p=0.06). CONCLUSION: The Fobi-Capella
      procedure without gastric ring promoted high frequency of intolerance to meat in
      general, especially for the red, chicken and fish, on this sequence; nausea was
      the most frequent symptom. These data suggest the need for adequate nutritional
      monitoring throughout the postoperative period.

PMID- 25861068
TI  - Post-bariatric surgery weight regain: evaluation of nutritional profile of
      candidate patients for endoscopic argon plasma coagulation.
AB  - BACKGROUND: Bariatric surgery is effective treatment for weight loss, but demand
      continuous nutritional care and physical activity. They regain weight happens
      with inadequate diets, physical inactivity and high alcohol consumption. AIM: To
      investigate in patients undergoing Roux-Y-of gastroplasty weight regain,
      nutritional deficiencies, candidates for the treatment with endoscopic argon
      plasma, the diameter of the gastrojejunostomy and the size of the gastric pouch
      at the time of treatment with plasma. METHODS: A prospective 59 patients non
      randomized study with no control group undergoing gastroplasty with recurrence of
      weight and candidates for the endoscopic procedure of argon plasma was realized.
      The surgical evaluation consisted of investigation of complications in the
      digestive system and verification of the increased diameter of the
      gastrojejunostomy. Nutritional evaluation was based on body mass index at the
      time of operation, in the minimum BMI achieved after and in which BMI was when
      making the procedure with plasma. The laboratory tests included hemoglobin,
      erythrocyte volume, ferritin, vitamin D, B12, iron, calcium, zinc and serum
      albumin. Clinical analysis was based on scheduled follow-up. RESULTS: Of the 59
      selected, five were men and 51 women; were included 49 people (four men and 44
      women) with all the complete data. The exclusion was due to the lack of some of
      the laboratory tests. Of this total 19 patients (38.7%) had a restrictive ring,
      while 30 (61.2%) did not. Iron deficiency anemia was common; 30 patients (61.2%)
      were below 30 with ferritin (unit); 35 (71.4%) with vitamin B12 were below 300
      pg/ml; vitamin D3 deficiency occurred in more than 90%; there were no cases of
      deficiency of protein, calcium and zinc; glucose levels were above 99 mg/dl in
      three patients (6.12%). Clinically all had complaints of labile memory,
      irritability and poor concentration. All reported that they stopped treatment
      with the multidisciplinary team in the first year after the operation.
      CONCLUSION: The profile of patients submitted to argon plasma procedure was:
      anastomosis in average with 27 mm; multiple nutritional deficiencies with
      predominance of iron deficiency anemia; ferritin below 30; vitamin B12 levels
      below 300 pg/ml; labile memory complaints, irritability and poor concentration.

PMID- 25861069
TI  - Weight loss and nutritional anemia in patients submitted to Roux-en-Y gastric
      bypass on use of vitamin and mineral supplementation.
AB  - BACKGROUND: Obesity is a chronic disease with high growth in population and
      bariatric surgery is currently considered the most effective treatment for weight
      reduction; on the other hand, nutritional deficiencies are observed after this
      procedure. AIM: To analyze weight loss progression and nutritional anemia in
      patients submitted to Roux-en-Y gastric bypass on use of vitamin and mineral
      supplementation. METHODS: Retrospective analysis of 137 patients of both sexes,
      aged between 18-60 years, using supplemental multivitamins and minerals, were
      included; personal information, anthropometric and laboratory data in the
      preoperative, 12, 24, 36 and 48 months postoperatively were collected. RESULTS:
      Postoperatively, in both sexes, occurred weight loss compared to the pre
      operative weight gain at 48 months and maintenance of body mass index. There was
      a decrease in the percentage of excess weight loss at 48 months postoperatively
      compared to the time of 12, 24 and 36 months in men and decreased at 48
      postoperative months compared to the time of 24 months in females. There was a
      decreased in serum ferritin in both sexes and increased serum iron at 48 months
      postoperatively in males. There was a decreased in vitamin B12 and folic acid
      increased serum at 48 postoperative months in females. CONCLUSIONS: Surgical
      treatment was effective for reducing weight, body mass index reduction and
      achievement of success in the late postoperative period along with multivitamin
      and mineral supplementation on prevention of serious nutritional deficiencies and
      anemia.

PMID- 25861070
TI  - Nutritional repercussions in patients submitted to bariatric surgery.
AB  - BACKGROUND: Few studies evaluated the association between nutritional disorders,
      quality of life and weight loss in patients undergoing bariatric surgery. AIM: To
      identify nutritional changes in patients undergoing bariatric surgery and
      correlate them with weight loss, control of comorbidities and quality of life.
      METHOD: A prospective cohort, analytical and descriptive study involving 59
      patients undergoing bariatric surgery was done. Data were collected
      preoperatively at three and six months postoperatively, evaluating nutritional
      aspects and outcomes using BAROS questionnaire. The data had a confidence
      interval of 95%. RESULTS: The majority of patients was composed of women, 47
      (79.7%), with 55.9% of the series with BMI between 40 to 49.9 kg/m(2). In the
      sixth month after surgery scores of quality of life were significantly higher
      than preoperatively (p<0.05) and 27 (67.5 %) patients had comorbidities resolved,
      48 (81.3 %) presented BAROS scores of very good or excellent. After three and six
      months of surgery 16 and 23 presented some nutritional disorder, respectively.
      There was no relationship between the loss of excess weight and quality of life
      among patients with or without nutritional disorders. CONCLUSION: Nutritional
      disorders are uncommon in the early postoperative period and, when present, have
      little or no influence on quality of life and loss of excess weight.

PMID- 25861071
TI  - Total clipless cholecystectomy by means of harmonic sealing.
AB  - BACKGROUND: In traditional laparoscopic cholecistectomy, the cystic duct and
      artery are commonly closed by metallic clips just before their division. Although
      the placement of these clips for occluding cystic artery and duct can be
      considered safe, biliary leaks and bleeding may occur especially by its
      dislodgement. AIM: To report a prospective case-series in total clipless
      cholecystectomy by means of harmonic shears for closure and division of the
      artery and cystic duct as well removal of the gallbladder from the liver.
      METHODS: Was evaluate a series of 125 patients who underwent laparoscopic
      cholecystectomy where the sealing and division of cystic artery and duct was
      carried out only by harmonic shears. The intact extracted gallbladder was
      submitted to a reverse pressure test for assessment of the technique safety by
      means of CO2 insuflation. RESULTS: The most common indication for surgery was
      gallstones. The mean operative time was 26 min and all gallbladders were
      dissected intact from the liver bed. There was no mortality and the overall
      morbidity rate was 0.8% with no hemorrhage or leaks. The reverse pressure test
      showed that all specimens support at least 36-mmHg of pressure without leaking.
      CONCLUSION: The harmonic shears is effective and safe in laparoscopic
      cholecystectomy as a sole instrument for sealing and division of the artery and
      cystic duct. The main advantages could be related to the safety and decreased
      operative time.

PMID- 25861072
TI  - Two port video-assisted gastrostomy and jejunostomy: technical simplification and
      clinical results.
AB  - BACKGROUND: Patients presenting upper gastrointestinal obstruction, difficulty or
      inability in swallowing, may need nutritional support which can be obtained
      through gastrostomy and jejunostomy. AIM: To describe the methods of gastrostomy
      and jejunostomy video-assisted, and to compare surgical approaches for video
      assisted laparoscopy and laparotomy in patients with advanced cancer of the
      esophagus and stomach, to establish enteral nutritional access. METHODS: Were
      used the video-assisted laparoscopic techniques for jejunostomy and gastrostomy
      and the same procedures performed by laparotomies. Comparatively, were analyzed
      the distribution of patients according to demographics, diagnosis and type of
      procedure. RESULTS: There were 36 jejunostomies (18 by laparotomy and 17
      laparoscopy) and 42 gastrostomies (21 on each side). In jejunostomy, relevant
      data were operating time of 132 min vs. 106 min (p = 0.021); reintroduction of
      diet: 3.3 days vs 2.1 days (p = 0.009); discharge: 5.8 days vs 4.3 days (p =
      0.044). In gastrostomy, relevant data were operative time of 122.6 min vs 86.2
      min (p = 0.012 and hospital discharge: 5.1 days vs 3.7 days (p = 0.016).
      CONCLUSION: The comparative analysis of laparotomy and video-assisted access to
      jejunostomies and gastrostomies concluded that video-assisted approach is
      feasible method, safe, fast, simple and easy, requires shorter operative time
      compared to laparotomy, enables diet start soon in compared to laparotomy, and
      also enables lower length of stay compared to laparotomy.

PMID- 25861073
TI  - New alternative for wound protection in laparoscopic colectomy.
AB  - BACKGROUND: Large number of surgical services use laparoscopy to approach the
      colon. One of the concerns on the resection using this way is the high rate of
      cancer relapse at in- and outlet site of the surgical instruments. AIM: To
      describe a protective device for surgical isolation in laparoscopic colectomy.
      METHODS: The device is made of sterile polyethylene plastic cover used to protect
      the fiber optic cable in laparoscopic surgery and one 20 Fr. urethral catheter
      working as a conduit. RESULTS: The device was used in six laparoscopic
      colectomies, three for adenocarcinoma of the colon and three for intestinal
      endometriosis. It was effective to avoid contact of the specimen with the
      abdominal wall, in order to reduce the risk of implantation of cancer or
      endometriotic cells and surgical site infection. The device was made
      intraoperative at all surgeries and allowed good visualization in laparoscopy and
      maintenance of the pneumoperitoneum. It cost R$ 22,00 (approximately US$ 10),
      R$14.50 related to the plastic cover and R$7.50, the urethral tube. The
      production time of the device and its installation in the abdominal cavity was
      measured in each procedure and was, on average, respectively, of 66 s and 25 s.
      CONCLUSION: The device proved to be feasible, not requiring any special training
      and can be performed by the surgical team itself, even at institutions with
      limited resources.

PMID- 25861074
TI  - Comparison of laparoscopic total gastrectomy and laparotomic total gastrectomy
      for gastric cancer.
AB  - BACKGROUND: The use of laparoscopy for the treatment of gastric cancer suffered
      some resistance among surgeons around the world, gaining strength in the past
      decade. However, its oncological safety and technical feasibility remain
      controversial. AIM: To describe the results from the clinical and
      anatomopathological point of view in the comparative evaluation between the
      surgical videolaparoscopic and laparotomic treatments of total gastrectomy with
      linphadenectomy at D2, resection R0. METHOD: Retrospective analyses and
      comparison data from patients submitted to total gastrectomy with D2
      linphadenectomy at a sole institution. The data of 111 patients showed that 64
      (57,7%) have been submitted to laparotomic gastrectomy and 47 (42,3%) to
      gastrectomy entirely performed through videolaparoscopy. All variables related to
      the surgery, post-operative follow-up and anatomopathologic findings have been
      evaluated. RESULTS: Among the studied variables, videolaparoscopy has shown a
      shorter surgical time and a more premature period for the introduction of oral
      and enteral nourishment than the open surgery. As to the amount of dissected
      limph nodes, there has been a significant difference towards laparotomy with
      p=0,014, but the average dissected limph nodes in both groups exceed 25 nodes as
      recommended by the JAGC. Was not found a significant difference between the
      studied groups as to age, ASA, type of surgery, need for blood transfusion, stage
      of the disease, Bormann classification, degree of differentiation, damage of the
      margins, further complications and death. CONCLUSION: The total gastrectomy with
      D2 lymphadenectomy performed by laparoscopy presented the same benefits known of
      laparotomy and with the advantages already established of minimally invasive
      surgery. It was done with less surgical time, less time for re-introduction of
      the oral and enteral diets and lower hospitalization time compared to laparotomy,
      without increasing postoperative complications.

PMID- 25861075
TI  - Fasting abbreviation among patients submitted to oncologic surgery: systematic
      review.
AB  - INTRODUCTION: The abbreviation of perioperative fasting among candidates to
      elective surgery have been associated with shorter hospital stay and decreased
      postoperative complications. OBJECTIVE: To conduct a systematic review from
      randomized controlled trials to detect whether the abbreviation of fasting is
      beneficial to patients undergoing cancer surgery compared to traditional fasting
      protocols. METHOD: A literature search was performed in electronic databases:
      MEDLINE (PubMed), SciELO, EMBASE and Cochrane, without time restriction. Were
      used the descriptors: "preoperative fasting", "cancer", "diet restriction" and
      "perioperative period". Randomized trials were included in adults of both sexes,
      with diagnosis of cancer. Exclusion criteria were: use of parenteral nutrition
      and publications in duplicate. All analyzes, selections and data extraction were
      done blinded manner by independent evaluators. RESULTS: Four studies were
      included, with a total of 150 patients, 128 with colorectal cancer and 22 gastric
      cancer. The articles were published from 2006 to 2013. The main outcome measures
      were heterogeneous, which impaired the unification of the results by means of
      meta-analysis. Compared to traditional protocols, patients undergoing fasting
      abbreviation with the administration of fluids containing carbohydrates had
      improvements in glycemic parameters (fasting glucose and insulin resistance),
      inflammatory markers (interleukin 6 and 10) and indicators of malnutrition (grip
      strength hand and CRP/albumin ratio), and shorter hospital stay. The
      methodological quality of the reviewed articles, however, suggests that the
      results should be interpreted with caution. CONCLUSION: The abbreviation of
      perioperative fasting in patients with neoplasm appears to be beneficial.

PMID- 25861076
TI  - Early surgical complications after gastric by-pass: a literature review.
AB  - INTRODUCTION: Gastric bypass is today the most frequently performed bariatric
      procedure,but, despite of it, several complications can occur with varied
      morbimortality. Probably all bariatric surgeons know these complications, but, as
      bariatric surgery continues to spread, general surgeon must be familiarized to it
      and its management. Gastric bypass complications can be divided into two groups:
      early and late complications, taking into account the two weeks period after the
      surgery. This paper will focus the early ones. METHOD: Literature review was
      carried out using Medline/PubMed, Cochrane Library, SciELO, and additional
      information on institutional sites of interest crossing the headings: gastric
      bypass AND complications; follow-up studies AND complications; postoperative
      complications AND anastomosis, Roux-en-Y; obesity AND postoperative
      complications. Search language was English. RESULTS: There were selected 26
      studies that matched the headings. Early complications included: anastomotic or
      staple line leaks, gastrointestinal bleeding, intestinal obstruction and
      incorrect Roux limb reconstruction. CONCLUSION: Knowledge on strategies on how to
      reduce the risk and incidence of complications must be acquired, and every
      surgeon must be familiar with these complications in order to achieve an earlier
      recognition and perform the best intervention.

PMID- 25861077
TI  - Current status of residency training in laparoscopic surgery in Brazil: a
      critical review.
AB  - INTRODUCTION: The surgeon's formation process has changed in recent decades. The
      increase in medical schools, new specialties and modern technologies induce an
      overhaul of medical education. Medical residency in surgery has established
      itself as a key step in the formation of the surgeon, and represents the ideal
      and natural way for teaching laparoscopy. However, the introduction of
      laparoscopic surgery in the medical residency programs in surgical specialties is
      insufficient, creating the need for additional training after its termination.
      OBJECTIVE: To review the surgical teaching ways used in services that published
      their results. METHODS: Survey of relevant publications in books, internet and
      databases in PubMed, Lilacs and Scielo through july 2014 using the headings:
      laparoscopy; simulation; education, medical; learning; internship and residency.
      RESULTS: The training method for medical residency in surgery focused on surgical
      procedures in patients under supervision, has proven successful in the era of
      open surgery. However, conceptually turns as a process of experimentation in
      humans. Psychomotor learning must not be developed directly to the patient.
      Training in laparoscopic surgery requires the acquisition of psychomotor skills
      through training conducted initially with surgical simulation. Platforms based
      teaching problem solving as the Fundamentals of Laparoscopic Surgery, developed
      by the American Society of Gastrointestinal Endoscopic Surgery and the
      Laparoscopic Surgical Skills proposed by the European Society of Endoscopic
      Surgery has been widely used both for education and for the accreditation of
      surgeons worldwide. CONCLUSION: The establishment of a more appropriate
      pedagogical process for teaching laparoscopic surgery in the medical residency
      programs is mandatory in order to give a solid surgical education and to
      determine a structured and safe professional activity.

PMID- 25861078
TI  - Splenic inferior pole.

PMID- 25861079
TI  - Gastrointestinal stromal tumor of the rectum treated with neoadjuvant Imatinib
      followed by transanal endoscopic microsurgery.

PMID- 25861080
TI  - Endoscopic hemostasis of a bleeding gastric gastrointestinal stromal tumor (GIST)
      with endoloop placement.

PMID- 25861081
TI  - Laparoscopic repair in simultaneous occurrence of recurrent chronic traumatic
      diaphragmatic hernia and transdiaphragmatic intercostal hernia.

PMID- 25861083
TI  - Spatial coherence-based batch-mode active learning for remote sensing image
      classification.
AB  - Batch-mode active learning (AL) approaches are dedicated to the training sample
      set selection for classification, regression, and retrieval problems, where a
      batch of unlabeled samples is queried at each iteration by considering both the
      uncertainty and diversity criteria. However, for remote sensing applications, the
      conventional methods do not consider the spatial coherence between the training
      samples, which will lead to the unnecessary cost. Based on the above two points,
      this paper proposes a spatial coherence-based batch-mode AL method. First, mean
      shift clustering is used for the diversity criterion, and thus the number of new
      queries can be varied in the different iterations. Second, the spatial coherence
      is represented by a two-level segmentation map which is used to automatically
      label part of the new queries. To get a stable and correct second-level
      segmentation map, a new merging strategy is proposed for the mean shift
      segmentation. The experimental results with two real remote sensing image data
      sets confirm the effectiveness of the proposed techniques, compared with the
      other state-of-the-art methods. 

PMID- 25861082
TI  - Using epigenomics data to predict gene expression in lung cancer.
AB  - BACKGROUND: Epigenetic alterations are known to correlate with changes in gene
      expression among various diseases including cancers. However, quantitative models
      that accurately predict the up or down regulation of gene expression are
      currently lacking. METHODS: A new machine learning-based method of gene
      expression prediction is developed in the context of lung cancer. This method
      uses the Illumina Infinium HumanMethylation450K Beadchip CpG methylation array
      data from paired lung cancer and adjacent normal tissues in The Cancer Genome
      Atlas (TCGA) and histone modification marker CHIP-Seq data from the ENCODE
      project, to predict the differential expression of RNA-Seq data in TCGA lung
      cancers. It considers a comprehensive list of 1424 features spanning the four
      categories of CpG methylation, histone H3 methylation modification, nucleotide
      composition, and conservation. Various feature selection and classification
      methods are compared to select the best model over 10-fold cross-validation in
      the training data set. RESULTS: A best model comprising 67 features is chosen by
      ReliefF based feature selection and random forest classification method, with AUC
      = 0.864 from the 10-fold cross-validation of the training set and AUC = 0.836
      from the testing set. The selected features cover all four data types, with
      histone H3 methylation modification (32 features) and CpG methylation (15
      features) being most abundant. Among the dropping-off tests of individual data
      type based features, removal of CpG methylation feature leads to the most
      reduction in model performance. In the best model, 19 selected features are from
      the promoter regions (TSS200 and TSS1500), highest among all locations relative
      to transcripts. Sequential dropping-off of CpG methylation features relative to
      different regions on the protein coding transcripts shows that promoter regions
      contribute most significantly to the accurate prediction of gene expression.
      CONCLUSIONS: By considering a comprehensive list of epigenomic and genomic
      features, we have constructed an accurate model to predict transcriptomic
      differential expression, exemplified in lung cancer.

PMID- 25861084
TI  - Effects of Visual Feedback Distortion on Gait Adaptation: Comparison of Implicit
      Visual Distortion Versus Conscious Modulation on Retention of Motor Learning.
AB  - GOAL: Visual feedback can be used during gait rehabilitation to improve the
      efficacy of training. We presented a paradigm called visual feedback distortion;
      the visual representation of step length was manipulated during treadmill
      walking. Our prior work demonstrated that an implicit distortion of visual
      feedback of step length entails an unintentional adaptive process in the
      subjects' spatial gait pattern. Here, we investigated whether the implicit visual
      feedback distortion, versus conscious correction, promotes efficient locomotor
      adaptation that relates to greater retention of a task. METHODS: Thirteen healthy
      subjects were studied under two conditions: (1) we implicitly distorted the
      visual representation of their gait symmetry over 14 min, and (2) with help of
      visual feedback, subjects were told to walk on the treadmill with the intent of
      attaining the gait asymmetry observed during the first implicit trial. After
      adaptation, the visual feedback was removed while subjects continued walking
      normally. Over this 6-min period, retention of preserved asymmetric pattern was
      assessed. RESULTS: We found that there was a greater retention rate during the
      implicit distortion trial than that of the visually guided conscious modulation
      trial. CONCLUSION: This study highlights the important role of implicit learning
      in the context of gait rehabilitation by demonstrating that training with
      implicit visual feedback distortion may produce longer lasting effects.
      SIGNIFICANCE: This suggests that using visual feedback distortion could improve
      the effectiveness of treadmill rehabilitation processes by influencing the
      retention of motor skills.

PMID- 25861085
TI  - Accurate vessel segmentation with constrained B-snake.
AB  - We describe an active contour framework with accurate shape and size constraints
      on the vessel cross-sectional planes to produce the vessel segmentation. It
      starts with a multiscale vessel axis tracing in a 3D computed tomography (CT)
      data, followed by vessel boundary delineation on the cross-sectional planes
      derived from the extracted axis. The vessel boundary surface is deformed under
      constrained movements on the cross sections and is voxelized to produce the final
      vascular segmentation. The novelty of this paper lies in the accurate contour
      point detection of thin vessels based on the CT scanning model, in the efficient
      implementation of missing contour points in the problematic regions and in the
      active contour model with accurate shape and size constraints. The main advantage
      of our framework is that it avoids disconnected and incomplete segmentation of
      the vessels in the problematic regions that contain touching vessels (vessels in
      close proximity to each other), diseased portions (pathologic structure attached
      to a vessel), and thin vessels. It is particularly suitable for accurate
      segmentation of thin and low contrast vessels. Our method is evaluated and
      demonstrated on CT data sets from our partner site, and its results are compared
      with three related methods. Our method is also tested on two publicly available
      databases and its results are compared with the recently published method. The
      applicability of the proposed method to some challenging clinical problems, the
      segmentation of the vessels in the problematic regions, is demonstrated with good
      results on both quantitative and qualitative experimentations; our segmentation
      algorithm can delineate vessel boundaries that have level of variability similar
      to those obtained manually. 

PMID- 25861086
TI  - A Two-Stage Geometric Method for Pruning Unreliable Links in Protein-Protein
      Networks.
AB  - Protein-protein interactions (PPIs) play essential roles for determining the
      outcomes of most of the cellular functions of the cell. Although the
      experimentally detected high-throughput PPI data promise new opportunities for
      the study of many biological mechanisms including cellular metabolism and protein
      functions, experimentally detected PPIs have high levels of false positive rate.
      Therefore, it is of high practical value to develop novel computational tools for
      pruning low-confidence PPIs. In this paper, we propose a new geometric approach
      called Leave-One-Out Logistic Metric Embedding (LOO-LME) for assessing the
      reliability of interactions. Unlike previous approaches which mainly seek to
      preserve the noisy topological information of the PPI networks in the embedding
      space, LOO-LME first transforms the learning task into an equivalent discriminant
      form, then directly deals with the uncertainty in PPI networks using a leave-one
      out-style approach. The experimental results show that LOO-LME substantially
      outperforms previous methods on PPI assessment problems. LOO-LME could thus
      facilitate further graph-based studies of PPIs and may help infer their hidden
      underlying biological knowledge.

PMID- 25861087
TI  - Tactile Feedback of Object Slip Facilitates Virtual Object Manipulation.
AB  - Recent advances in myoelectric prosthetic technology have enabled more complex
      movements and interactions with objects, but the lack of natural haptic feedback
      makes object manipulation difficult to perform. Our research effort aims to
      develop haptic feedback systems for improving user performance in object
      manipulation. Specifically, in this work, we explore the effectiveness of
      vibratory tactile feedback of slip information for grasping objects without
      slipping. A user interacts with a virtual environment to complete a virtual grasp
      and hold task using a Sensable Phantom. Force feedback simulates contact with
      objects, and vibratory tactile feedback alerts the user when a virtual object is
      slipping from the grasp. Using this task, we found that tactile feedback
      significantly improved a user's ability to detect and respond to slip and to
      recover the slipping object when visual feedback was not available. This
      advantage of tactile feedback is especially important in conjunction with force
      feedback, which tends to reduce a subject's grasping forces and therefore
      encourage more slips. Our results demonstrate the potential of slip feedback to
      improve a prosthesis user's ability to interact with objects with less visual
      attention, aiding in performance of everyday manipulation tasks.

PMID- 25861088
TI  - Comparison of Seven Methods for Boolean Factor Analysis and Their Evaluation by
      Information Gain.
AB  - An usual task in large data set analysis is searching for an appropriate data
      representation in a space of fewer dimensions. One of the most efficient methods
      to solve this task is factor analysis. In this paper, we compare seven methods
      for Boolean factor analysis (BFA) in solving the so-called bars problem (BP),
      which is a BFA benchmark. The performance of the methods is evaluated by means of
      information gain. Study of the results obtained in solving BP of different levels
      of complexity has allowed us to reveal strengths and weaknesses of these methods.
      It is shown that the Likelihood maximization Attractor Neural Network with
      Increasing Activity (LANNIA) is the most efficient BFA method in solving BP in
      many cases. Efficacy of the LANNIA method is also shown, when applied to the real
      data from the Kyoto Encyclopedia of Genes and Genomes database, which contains
      full genome sequencing for 1368 organisms, and to text data set R52 (from Reuters
      21578) typically used for label categorization. 

PMID- 25861089
TI  - In-Body to On-Body Ultrawideband Propagation Model Derived From Measurements in
      Living Animals.
AB  - Ultrawideband (UWB) radio technology for wireless implants has gained significant
      attention. UWB enables the fabrication of faster and smaller transceivers with
      ultralow power consumption, which may be integrated into more sophisticated
      implantable biomedical sensors and actuators. Nevertheless, the large path loss
      suffered by UWB signals propagating through inhomogeneous layers of biological
      tissues is a major hindering factor. For the optimal design of implantable
      transceivers, the accurate characterization of the UWB radio propagation in
      living biological tissues is indispensable. Channel measurements in phantoms and
      numerical simulations with digital anatomical models provide good initial insight
      into the expected path loss in complex propagation media like the human body, but
      they often fail to capture the effects of blood circulation, respiration, and
      temperature gradients of a living subject. Therefore, we performed UWB channel
      measurements within 1-6 GHz on two living porcine subjects because of the
      anatomical resemblance with an average human torso. We present for the first
      time, a path loss model derived from these in vivo measurements, which includes
      the frequency-dependent attenuation. The use of multiple on-body receiving
      antennas to combat the high propagation losses in implant radio channels was also
      investigated.

PMID- 25861090
TI  - DBN-Extended: A Dynamic Bayesian Network Model Extended With Temporal
      Abstractions for Coronary Heart Disease Prognosis.
AB  - Dynamic Bayesian networks (DBNs) are temporal probabilistic graphical models that
      model temporal events and their causal and temporal dependencies. Temporal
      abstraction (TA) is a knowledge-based process that abstracts raw temporal data
      into higher level interval-based concepts. In this paper, we present an extended
      DBN model that integrates TA methods with DBNs applied for prognosis of the risk
      for coronary heart disease. More specifically, we demonstrate the derivation of
      TAs from data, which are used for building the network structure. We use machine
      learning algorithms to learn the parameters of the model through data. We apply
      the extended model to a longitudinal medical dataset and compare its performance
      to the performance of a DBN implemented without TAs. The results we obtain
      demonstrate the predictive accuracy of our model and the effectiveness of our
      proposed approach.

PMID- 25861091
TI  - Wearable Monitoring of Physical Functioning and Disability Changes, Circadian
      Rhythms and Sleep Patterns in Nursing Home Residents.
AB  - Sleep problems and disrupted circadian rhythms are common among older adults and
      may be associated with several health issues and physical functioning status.
      Wearable continuous monitoring of physical activity enables unobtrusive
      monitoring of circadian activity and sleep patterns. The objective of this
      retrospective study was to analyze whether physical functioning status
      (Activities of Daily Living assessment of Resident Assessment Instrument) is
      associated with diurnal activity rhythm and sleep patterns measured with wearable
      activity sensor in nursing home residents during their normal daily life.
      Continuous activity data were collected by the wearable sensor from 16 nursing
      home residents (average age of 90.7 years, seven demented subjects, one female)
      in their daily life over several months (12-18 months). The subjects' physical
      activity and sleep were quantified by several parameters from the activity data.
      In the cross-sectional analysis, physical functioning status was associated with
      the strength (RHO = 0.78, ) and the stability (RHO = 0.72, ) of the activity
      rhythm when the level of dementia was not controlled. In the longitudinal
      analysis (12-18 months), at an individual level the activity rhythm indices and
      activity level had the strongest correlations with changes in physical
      functioning but the associations were to some extent individual. In these long
      term case recordings, decrease in the physical functioning was most strongly
      associated with decreasing levels of activity, stability, and strength of the
      activity rhythm, and with increasing fragmentation of rhythm and daytime
      passivity. Daily wearable monitoring of physical activity may hence reveal
      information about functioning state and health of older adults. However, since
      the changes in activity patterns implying changes in physical functioning status
      may not be consistent between the individuals, a multivariate approach is
      recommended for monitoring of these changes by continuous physical activity
      measurement.

PMID- 25861092
TI  - Geographical Topics Learning of Geo-Tagged Social Images.
AB  - With the availability of cheap location sensors, geotagging of images in online
      social media is very popular. With a large amount of geo-tagged social images, it
      is interesting to study how these images are shared across geographical regions
      and how the geographical language characteristics and vision patterns are
      distributed across different regions. Unlike textual document, geo-tagged social
      image contains multiple types of content, i.e., textual description, visual
      content, and geographical information. Existing approaches usually mine
      geographical characteristics using a subset of multiple types of image contents
      or combining those contents linearly, which ignore correlations between different
      types of contents, and their geographical distributions. Therefore, in this
      paper, we propose a novel method to discover geographical characteristics of geo
      tagged social images using a geographical topic model called geographical topic
      model of social images (GTMSIs). GTMSI integrates multiple types of social image
      contents as well as the geographical distributions, in which image topics are
      modeled based on both vocabulary and visual features. In GTMSI, each region of
      the image would have its own topic distribution, and hence have its own language
      model and vision pattern. Experimental results show that our GTMSI could identify
      interesting topics and vision patterns, as well as provide location prediction
      and image tagging. 

PMID- 25861093
TI  - Intensity Estimation of Spontaneous Facial Action Units Based on Their Sparsity
      Properties.
AB  - Automatic measurement of spontaneous facial action units (AUs) defined by the
      facial action coding system (FACS) is a challenging problem. The recent FACS user
      manual defines 33 AUs to describe different facial activities and expressions. In
      spontaneous facial expressions, a subset of AUs are often occurred or activated
      at a time. Given this fact that AUs occurred sparsely over time, we propose a
      novel method to detect the absence and presence of AUs and estimate their
      intensity levels via sparse representation (SR). We use the robust principal
      component analysis to decompose expression from facial identity and then estimate
      the intensity of multiple AUs jointly using a regression model formulated based
      on dictionary learning and SR. Our experiments on Denver intensity of spontaneous
      facial action and UNBC-McMaster shoulder pain expression archive databases show
      that our method is a promising approach for measurement of spontaneous facial
      AUs. 

PMID- 25861094
TI  - Effects of Combined Exposure to Lead and High-Fat Diet on Bone Quality in
      Juvenile Male Mice.
AB  - BACKGROUND: Lead (Pb) exposure and obesity are co-occurring risk factors for
      decreased bone mass in the young, particularly in low socioeconomic communities.
      OBJECTIVES: The goal of this study was to determine whether the comorbidities of
      Pb exposure and high-fat diet-induced obesity amplify skeletal deficits
      independently associated with each of these risk factors, and to explore
      associated mechanisms of the observed deficiencies. METHODS: Five-week-old male
      C57BL/6J mice were placed on low-fat (10% kcal, LFD) or high-fat (60% kcal, HFD)
      diets for 12 weeks. Mice were exposed to lifetime Pb (50 ppm) through drinking
      water. RESULTS: HFD was associated with increased body mass and glucose
      intolerance. Both HFD and Pb increased fasting glucose and serum leptin levels.
      Pb and HFD each reduced trabecular bone quality and together had a further
      detrimental effect on these bone parameters. Mechanical bone properties of
      strength were depressed in Pb-exposed bones, but HFD had no significant effect.
      Both Pb and HFD altered progenitor cell differentiation, promoting
      osteoclastogenesis and increasing adipogenesis while suppressing
      osteoblastogenesis. In support of this lineage shift being mediated through
      altered Wnt signaling, Pb and non-esterified fatty acids in MC3T3 cells increased
      in vitro PPAR-gamma activity and inhibited beta-catenin activity. Combining Pb
      and non-esterified fatty acids enhanced these effects. CONCLUSIONS: Pb and HFD
      produced selective deficits in bone accrual that were associated with alterations
      in progenitor cell activity that may involve reduced Wnt signaling. This study
      emphasizes the need to assess toxicants together with other risk factors relevant
      to human health and disease.

PMID- 25861095
TI  - Effect of Organic Diet Intervention on Pesticide Exposures in Young Children
      Living in Low-Income Urban and Agricultural Communities.
AB  - BACKGROUND: Recent organic diet intervention studies suggest that diet is a
      significant source of pesticide exposure in young children. These studies have
      focused on children living in suburban communities. OBJECTIVES: We aimed to
      determine whether consuming an organic diet reduced urinary pesticide metabolite
      concentrations in 40 Mexican-American children, 3-6 years of age, living in
      California urban and agricultural communities. METHODS: In 2006, we collected
      urine samples over 16 consecutive days from children who consumed conventionally
      grown food for 4 days, organic food for 7 days, and then conventionally grown
      food for 5 days. We measured 23 metabolites, reflecting potential exposure to
      organophosphorous (OP), pyrethroid, and other pesticides used in homes and
      agriculture. We used linear mixed-effects models to evaluate the effects of diet
      on urinary metabolite concentrations. RESULTS: For six metabolites with detection
      frequencies > 50%, adjusted geometric mean concentrations during the organic
      phase were generally lower for all children, and were significant for total
      dialkylphosphates (DAPs) and dimethyl DAPs (DMs; metabolites of OP insecticides)
      and 2,4-D (2,4-dichlorophenoxyacetic acid, a herbicide), with reductions of 40%,
      49%, and 25%, respectively (p < 0.01). Chemical-specific metabolite
      concentrations for several OP pesticides, pyrethroids, and herbicides were either
      infrequently detected and/or not significantly affected by diet. Concentrations
      for most of the frequently detected metabolites were generally higher in Salinas
      compared with Oakland children, with DMs and metolachlor at or near significance
      (p = 0.06 and 0.03, respectively). CONCLUSION: An organic diet was significantly
      associated with reduced urinary concentrations of nonspecific dimethyl OP
      insecticide metabolites and the herbicide 2,4-D in children. Additional research
      is needed to clarify the relative importance of dietary and non-dietary sources
      of pesticide exposures to young children.

PMID- 25861096
TI  - Use of Morphology and Endocrinology to Predict Sex in California Sheephead:
      Evidence of Altered Timing of Sex Change at Santa Catalina Island, California.
AB  - To estimate the health of the California sheephead Semicossyphus pulcher fishery,
      a 2004 stock assessment used available biological data that were collected
      decades prior to an increase in fishing pressure. However, a recent study has
      found that sex ratios, growth rates, survivorship, and average sizes of females
      and males have changed in response to size-selective fishing in some California
      sheephead populations. To better understand the potential changes in protogynous
      California sheephead, this study sought to determine (1) whether external
      morphology was still an accurate method of predicting sex in sexually dimorphic
      California sheephead at Santa Catalina Island, California, and (2) whether
      nonlethal blood sampling and plasma hormone analysis could be used to predict sex
      for future stock assessments. Sex was determined using gonadal histology and
      compared with several specific external morphological characters. Estradiol and
      11-ketotestosterone plasma concentrations were also compared across sexed
      individuals. The rate of error when using external morphology alone to predict
      sex was 58%. In contrast, sex steroid concentrations varied significantly across
      sexes; estradiol concentrations were significantly greater in females than in
      transitioning and male individuals during the breeding season, and 11
      ketotestosterone concentrations were significantly lower among females. Gonadal
      histology showed that 21% of the fish caught during the breeding season were
      classified as transitional, in stark contrast to historical data. The inability
      to accurately predict sex using external morphology alone suggests that commonly
      used methods of surveying California sheephead populations (e.g., diver surveys)
      may be inaccurate. Nonlethal blood sampling and subsequent plasma hormone
      analysis may offer an alternative method for assessing sex in California
      sheephead. Because California sheephead are not reproductively functional during
      transition and because we found such a large proportion in transition during the
      breeding season at Santa Catalina Island, we believe there is a need for
      continued assessment of the reproductive potential in this population of
      California sheephead.

PMID- 25861097
TI  - The responsibility of advancing continuing professional development and
      continuing education globally.

PMID- 25861098
TI  - Examining pharmacy workforce issues in the United States and the United kingdom.
AB  - OBJECTIVE: To examine available data and actions surrounding current pharmacy
      workforce issues in the United States and United Kingdom. METHODS: Published
      pharmacy workforce data from the United States and United Kingdom were gathered
      from various sources, including PUBMED, Internet search engines, and pharmacy
      organization websites. Data was collated from additional sources including
      scientific literature, internal documents, news releases, and policy positions.
      RESULTS: The number of colleges and schools of pharmacy has expanded by
      approximately 50% in both the United States and United Kingdom over the previous
      decade. In the United States, continued demand for the pharmacy workforce has
      been forecasted, but this need is based on outdated supply figures and
      assumptions for economic recovery. In the United Kingdom, workforce modeling has
      predicted a significant future oversupply of pharmacists, and action within the
      profession has attempted to address the situation through educational planning
      and regulation. CONCLUSION: Workforce planning is an essential task for
      sustaining a healthy profession. Recent workforce planning mechanisms in the
      United Kingdom may provide guidance for renewed efforts within the profession in
      the United States.

PMID- 25861099
TI  - A randomized prospective study on outcomes of an empathy intervention among
      second-year student pharmacists.
AB  - OBJECTIVE: To determine the impact of a single, 3-day intervention on empathy
      levels as measured by the validated Jefferson Scale of Empathy-Health Profession
      Students version (JSE-HPS). METHODS: Forty second-year student pharmacists were
      recruited to participate in a non-blinded prospective study. Subjects were
      randomized to an intervention group (n=20) or control group (n=20) and completed
      the JSE-HPS at baseline, 7 days postintervention, and 90 days postintervention.
      The intervention group consisted of a 3-day simulation, each day including a
      designated activity with loss of dominant hand usage, vision, and speech.
      RESULTS: The 3-day simulation increased empathy levels in the intervention group
      compared to the control group 7 days postintervention (p=0.035). However, there
      were no effects on empathy levels 90 days postintervention (p=0.38). CONCLUSION:
      Empathy scores increased but were not sustained in the long-term with a 3-day
      empathy intervention.

PMID- 25861100
TI  - A psychometric evaluation of an advanced pharmacy practice experience clinical
      competency framework.
AB  - OBJECTIVE: To assess the psychometric properties of the clinical competency
      framework known as the System of Universal Clinical Competency Evaluation in the
      Sunshine State (SUCCESS), including its internal consistency and content,
      construct, and criterion validity. METHODS: Sub-competency items within each
      hypothesized competency pair were subjected to principal components factor
      analysis to demonstrate convergent and discriminant validity. Varimax rotation
      was conducted for each competency pair (eg, competency 1 vs competency 2,
      competency 1 vs competency 3, competency 2 vs competency 3). Internal consistency
      was evaluated using Cronbach alpha. RESULTS: Of the initial 78 pairings, 44 (56%)
      demonstrated convergent and discriminant validity. Five pairs of competencies
      were unidimensional. Of the 34 pairs where at least 1 competency was
      multidimensional, most (91%) were from competencies 7, 11, and 12, indicating
      modifications were warranted in those competencies. After reconfiguring the
      competencies, 76 (94%) of the 81 pairs resulted in 2 factors as required. A
      unidimensional factor emerged when all 13 of the competencies were entered into a
      factor analysis. The internal consistency of all of the competencies was
      satisfactory. CONCLUSION: Psychometric evaluation shows the SUCCESS framework
      demonstrates adequate reliability and validity for most competencies. However, it
      also provides guidance where improvements are needed as part of a continuous
      quality improvement program.

PMID- 25861101
TI  - An exploratory analysis of personality, attitudes, and study skills on the
      learning curve within a team-based learning environment.
AB  - OBJECTIVE: To examine factors that determine the interindividual variability of
      learning within a team-based learning environment. METHODS: Students in a
      pharmacokinetics course were given 4 interim, low-stakes cumulative assessments
      throughout the semester and a cumulative final examination. Students' Myers
      Briggs personality type was assessed, as well as their study skills, motivations,
      and attitudes towards team-learning. A latent curve model (LCM) was applied and
      various covariates were assessed to improve the regression model. RESULTS: A
      quadratic LCM was applied for the first 4 assessments to predict final
      examination performance. None of the covariates examined significantly impacted
      the regression model fit except metacognitive self-regulation, which explained
      some of the variability in the rate of learning. There were some correlations
      between personality type and attitudes towards team learning, with introverts
      having a lower opinion of team-learning than extroverts. CONCLUSION: The LCM
      could readily describe the learning curve. Extroverted and introverted
      personality types had the same learning performance even though preference for
      team-learning was lower in introverts. Other personality traits, study skills, or
      practice did not significantly contribute to the learning variability in this
      course.

PMID- 25861102
TI  - Comparison of answer-until-correct and full-credit assessments in a team-based
      learning course.
AB  - OBJECTIVE: To assess the impact of awarding partial credit to team assessments on
      team performance and on quality of team interactions using an answer-until
      correct method compared to traditional methods of grading (multiple-choice, full
      credit). METHODS: Subjects were students from 3 different offerings of an
      ambulatory care elective course, taught using team-based learning. The control
      group (full-credit) consisted of those enrolled in the course when traditional
      methods of assessment were used (2 course offerings). The intervention group
      consisted of those enrolled in the course when answer-until-correct method was
      used for team assessments (1 course offering). Study outcomes included student
      performance on individual and team readiness assurance tests (iRATs and tRATs),
      individual and team final examinations, and student assessment of quality of team
      interactions using the Team Performance Scale. RESULTS: Eighty-four students
      enrolled in the courses were included in the analysis (full-credit, n=54; answer
      until-correct, n=30). Students who used traditional methods of assessment
      performed better on iRATs (full-credit mean 88.7 (5.9), answer-until-correct mean
      82.8 (10.7), p<0.001). Students who used answer-until-correct method of
      assessment performed better on the team final examination (full-credit mean 45.8
      (1.5), answer-until-correct 47.8 (1.4), p<0.001). There was no significant
      difference in performance on tRATs and the individual final examination. Students
      who used the answer-until-correct method had higher quality of team interaction
      ratings (full-credit 97.1 (9.1), answer-until-correct 103.0 (7.8), p=0.004).
      CONCLUSION: Answer-until-correct assessment method compared to traditional, full
      credit methods resulted in significantly lower scores for iRATs, similar scores
      on tRATs and individual final examinations, improved scores on team final
      examinations, and improved perceptions of the quality of team interactions.

PMID- 25861103
TI  - Pharmacy students' preference for using mobile devices in a clinical setting for
      practice-related tasks.
AB  - OBJECTIVE: To examine pharmacy students' ownership of, use of, and preference for
      using a mobile device in a practice setting. METHODS: Eighty-one pharmacy
      students were recruited and completed a pretest that collected information about
      their demographics and mobile devices and also had them rank the iPhone, iPad
      mini, and iPad for preferred use in a pharmacy practice setting. Students used
      the 3 devices to perform pharmacy practice-related tasks and then completed a
      posttest to again rank the devices for preferred use in a pharmacy practice
      setting. RESULTS: The iPhone was the most commonly owned mobile device (59.3% of
      students), and the iPad mini was the least commonly owned (18.5%). About 70% of
      the students used their mobile devices at least once a week in a pharmacy
      practice setting. The iPhone was the most commonly used device in a practice
      setting (46.9% of students), and the iPod Touch was the least commonly used
      device (1.2%). The iPad mini was the most preferred device for use in a pharmacy
      practice setting prior to performing pharmacy practice-related tasks (49.4% of
      students), and was preferred by significantly more students after performing the
      tasks (70.4%). CONCLUSION: Pharmacy students commonly use their mobile devices in
      pharmacy practice settings and most selected the iPad mini as the preferred
      device for use in a practice setting even though it was the device owned by the
      fewest students.

PMID- 25861104
TI  - Scholarly contributions of required senior research projects in a doctor of
      pharmacy curriculum.
AB  - OBJECTIVE: To determine dissemination outcomes and faculty perceptions of senior
      research projects conducted from 2008 to 2011 by PharmD students in a curricular
      pathway focused on direct patient care. METHODS: Preceptors' reported
      dissemination outcomes of research projects were surveyed and their perceptions
      of the precepting experience were rated using a web-based survey. Results were
      compared to those from an earlier pharmaceutical care cohort (2002-2007) and a
      combined cohort of 2, more research-intensive curricular pathways at the school.
      RESULTS: The overall response rate was 90.2%. Project dissemination included
      61.3% at an institutional forum, 42.3% as a submitted publication, 37.8% as a
      poster, and 4.5% as an oral presentation. Projects completed from 2008-2011 were
      significantly more likely than those from 2002-2007 to be submitted for
      publication (42.3% vs 10.7%, p<0.001) and published (28.8% vs 5.3%, p<0.001).
      Most preceptors found their research projects valuable to them professionally
      (88.3%) and to their own or another institution (83.5% and 78.5%, respectively).
      Ninety-five percent of preceptors would precept again. CONCLUSION: Dissemination
      rates for pharmaceutical care projects increased over time. Despite modest
      dissemination levels, the majority of preceptors agreed that required student
      research projects provide a valuable learning experience for students.

PMID- 25861105
TI  - The impact of blended learning on student performance in a cardiovascular
      pharmacotherapy course.
AB  - OBJECTIVE: To examine student engagement with, perception of, and performance
      resulting from blended learning for venous thromboembolism in a required
      cardiovascular pharmacotherapy course for second-year students. DESIGN: In 2013,
      key foundational content was packaged into an interactive online module for
      students to access prior to coming to class; class time was dedicated to active
      learning exercises. ASSESSMENT: Students who accessed all online module segments
      participated in more in class clicker questions (p=0.043) and performed better on
      the examination (p=0.023). There was no difference in clicker participation or
      examination performance based on time of module access (prior to or after class).
      The majority of participants agreed or strongly agreed that foundational content
      learned prior to class, applied activities during class, and content-related
      questions in the online module greatly enhanced learning. CONCLUSION: This study
      highlights the importance of integrating online modules with classroom learning
      and the role of blended learning in improving academic performance.

PMID- 25861106
TI  - Active learning through a debate series in a first-year pharmacy self-care
      course.
AB  - OBJECTIVE: To evaluate the usefulness of formal debates in the pharmacy classroom
      as a way to learn course material and as a tool for developing competency in
      essential skills including critical thinking, communication, public speaking,
      research methods, and teamwork. DESIGN: Debates were incorporated into a self
      care course, where students were assigned different debate topics focused on
      controversial issues. Quantitative analysis was completed to assess debate style
      learning, knowledge about the subjects presented, and the impact on necessary
      skills. ASSESSMENT: Quizzes given before and after debates showed up to a 36%
      improvement in grades and up to a 31% change in opinions on the topic. Students
      assessed themselves as more competent in the skill sets at the completion of the
      debate series. CONCLUSION: Incorporation of debates into didactic style courses
      offers students an opportunity to improve upon skills that will help them succeed
      as pharmacists.

PMID- 25861107
TI  - A course-based cross-cultural interaction among pharmacy students in Qatar and
      Canada.
AB  - OBJECTIVE: To develop, implement, and evaluate a course-based, cross-cultural
      student interaction using real-time videoconferencing between universities in
      Canada and Qatar. DESIGN: A professional skills simulation practice session on
      smoking cessation was run for students in Qatar (n=22) and Canada (n=22).
      Students role played cases in small group situations and then interacted with
      colleagues from the other country regarding culturally challenging situations and
      communication strategies. ASSESSMENT: Students were assessed on analytical
      content and communication skills through faculty member and peer evaluation.
      Cultural competency outcomes were assessed using a postsession survey. Overall,
      92.3% of respondents agreed that learning was enhanced through the cross-cultural
      exchange, and 94.9% agreed that insight was gained into the health-related issues
      and needs of people from another culture. CONCLUSION: A course-based, cross
      cultural interaction was an effective method to incorporate cultural competency
      principles into student learning. Future initiatives should increase direct
      student interaction and focus on culturally sensitive topics.

PMID- 25861109
TI  - Incorporation of hands-on sterile technique instruction in an introductory
      pharmacy practice experience.
AB  - OBJECTIVE: To examine sterile technique and basic sterile compounding procedures
      among third-year pharmacy students. DESIGN: Third year pharmacy students
      participating in an introductory pharmacy practice experience (IPPE) in 2012
      (n=126) and 2013 (n=119) performed a modified low-risk compounded sterile product
      (CSP) media fill challenge test, then prepared a 5 mg/mL vancomycin solution that
      was subsequently analyzed for accuracy. ASSESSMENT: To identify deficiencies in
      sterile procedures, students were observed while performing a modified low-risk
      CSP media fill challenge test. In the first year of conducting the challenge test
      (2012), 3 deficiencies were identified: hand washing before compounding, cleaning
      items with alcohol prior to start, and cleaning work area upon completion. In
      2013, significant improvements were observed in these 3 areas after students
      watched a demonstration video. Examination of CSPs revealed less than 1%
      contamination in both years. Analysis of compounded vancomycin solutions showed
      that 84% and 71% of students prepared solutions in 2012 and 2013, respectively,
      were within 10% of the targeted final concentration. CONCLUSION: Hands-on sterile
      compounding exercises are typically delivered early in the pharmacy professional
      curriculum with minimal reinforcement in subsequent years. Providing
      opportunities for advanced pharmacy students to refresh and practice sterile
      compounding procedures allows students to refine their skills before entering
      pharmacy practice.

PMID- 25861108
TI  - Teaching and learning health literacy in a doctor of pharmacy program.
AB  - OBJECTIVE: To evaluate the impact of health literacy (HL) activities incorporated
      into a required, first professional year (P1), patient-centered communication
      course on pharmacy students' knowledge, abilities, confidence, and attitudes
      related to HL. DESIGN: Integrated, active-learning HL activities were
      incorporated into the course. Students' knowledge and abilities were assessed
      with course evaluations. Students' knowledge, confidence levels, and attitudes
      were evaluated by a precourse and postcourse survey. Third professional year (P3)
      students who did not complete HL activities were also surveyed. ASSESSMENT:
      Almost all students "met" or "exceeded" expectations (the top 2 levels of
      achievement on the objective structured clinical examination (OSCE) grading
      rubrics) on HL course evaluations. Survey results showed significant improvement
      in P1 students' knowledge, confidence, and attitudes related to HL after
      completing the course. First year students (postcourse) rated their confidence
      levels and attitudes higher than P3 students. CONCLUSION: The use of integrated,
      active-learning activities is effective at improving P1 pharmacy students'
      knowledge, abilities, confidence levels, and attitudes related to HL.

PMID- 25861110
TI  - An asynchronous learning approach for the instructional component of a dual
      campus pharmacy resident teaching program.
AB  - OBJECTIVE: To describe the shift to an asynchronous online approach for pedagogy
      instruction within a pharmacy resident teaching program offered by a dual-campus
      college. DESIGN: The pedagogy instruction component of the teaching program (Part
      I) was redesigned with a focus on the content, delivery, and coordination of the
      learning environment. Asynchronous online learning replaced distance technology
      or lecture capture. Using a pedagogical content knowledge framework, residents
      participated in self-paced online learning using faculty recordings, readings,
      and discussion board activities. A learning management system was used to assess
      achievement of learning objectives and participation prior to progressing to the
      teaching experiences component of the teaching program (Part II). ASSESSMENT:
      Evaluation of resident pedagogical knowledge development and participation in
      Part I of the teaching program was achieved through the learning management
      system. Participant surveys and written reflections showed general satisfaction
      with the online learning environment. Future considerations include addition of a
      live orientation session and increased faculty presence in the online learning
      environment. CONCLUSION: An online approach framed by educational theory can be
      an effective way to provide pedagogy instruction within a teaching program.

PMID- 25861111
TI  - Active student engagement in curriculum development.

PMID- 25861112
TI  - Utility of Classical alpha-Taxonomy for Biodiversity of Aquatic Nematodes.
AB  - "Classical alpha-taxonomy" has different interpretations. Therefore, within the
      framework of an integrated taxonomic approach it is not relevant to divide
      taxonomy in different components, each being allocated a different weight of
      importance. Preferably, taxonomy should be seen in a holistic way, including the
      act of delimiting and describing taxa, based on different features and available
      methods, and taxonomy can not be interpreted without looking at evolutionary
      relationships. The concept of diversity itself is quite diverse as is the measure
      of diversity. Taxonomic descriptions of free-living aquatic nematodes are very
      valuable as they provide basic phenotypic information that is necessary for the
      functional ecological, behavioral, and evolutionary interpretation of data
      gathered from molecular analyses and of the organism as a whole. In general,
      molecular taxonomic analyses have the advantage of being much faster and of being
      able to deal with a larger number of specimens but also possess the important
      advantage of dealing with a huge amount of features compared to the morphology
      based approach. However, just as morphological studies, molecular analyses deal
      only with partial of an organism. 

PMID- 25861114
TI  - Free-living nematodes in the freshwater food web: a review.
AB  - Free-living nematodes are well-recognized as an abundant and ubiquitous component
      of benthic communities in inland waters. Compelling evidence from soil and marine
      ecosystems has highlighted the importance of nematodes as trophic intermediaries
      between microbial production and higher trophic levels. However, the paucity of
      empirical evidence of their role in freshwater ecosystems has hampered their
      inclusion in our understanding of freshwater food web functioning. This
      literature survey provides an overview of research efforts in the field of
      freshwater nematode ecology and of the complex trophic interactions between free
      living nematodes and microbes, other meiofauna, macro-invertebrates, and fishes.
      Based on an analysis of the relevant literature and an appreciation of the
      potential of emerging approaches for the evaluation of nematode trophic ecology,
      we point out research gaps and recommend relevant directions for further
      research. The latter include (i) interactions of nematodes with protozoans and
      fungi; (ii) nonconsumptive effects of nematodes on microbial activity and the
      effects of nematodes on associated key ecosystem processes (decomposition,
      primary production); and (iii) the feeding selectivity and intraspecific feeding
      variability of nematodes and their potential impacts on the structure of benthic
      communities. 

PMID- 25861115
TI  - Effect of Storage Environment on Hatching of the Cyst Nematode Globodera
      ellingtonae.
AB  - Globodera spp. eggs go through a diapause, which remains dormant until favorable
      hatching conditions are reached. Because of the regulatory concerns with cyst
      nematodes, it is often only possible to rear eggs for research in the greenhouse.
      However, hatch is often lower for greenhouse-produced eggs than for eggs obtained
      from the field. The goal of this research was to determine storage conditions for
      Globodera ellingtonae eggs produced in the greenhouse that would increase
      percentage hatch. Over 3 yr, G. ellingtonae greenhouse-produced eggs were stored
      in different environments (-20 degrees C, 4 degrees C, room temperature, and the
      field) in either dry or moist soil. Percentage hatch after exposure to the
      different environments was determined in potato root diffusate. Across two
      experiments, field-produced eggs had higher hatch rates (65.2%) than greenhouse
      produced eggs (10.4%). Temperature did not have an appreciable influence on hatch
      of eggs stored dry in two experiments (2.8% to 8.4% and 3.8% to 8.6%), but hatch
      of eggs stored in moist soil was significantly higher than in dry soil at all
      temperatures except -20 degrees C (26.8% and 28.7%). However, the ability of G.
      ellingtonae greenhouse-, microplot-, and field-produced eggs to reproduce on
      potato in field microplots was not different. Although it may not be possible to
      produce G. ellingtonae eggs in the greenhouse that have the magnitude of hatch as
      those produced in the field, hatching can be greatly increased by storing eggs in
      moist soil at either 4 degrees C or room temperature. 

PMID- 25861113
TI  - Experimental studies with nematodes in ecotoxicology: an overview.
AB  - With respect to their high abundances, their role as intermediaries between
      microorganisms and higher trophic levels, and their ubiquitous occurrence in all
      habitats, nematodes are of strong potential interest as environmental indicators.
      Ecotoxicological methods to evaluate the risk of anthropogenic pollutants on
      ecosystems require both in vitro and in vivo toxicity tests to investigate either
      mechanisms or pathways of toxicity and to set accurate toxicity thresholds. For
      this, the interest in nematodes as model organisms in ecotoxicology increased
      over the past few decades and existing appropriate experimental methods are
      reviewed in this manuscript. An overview of the various existing ecotoxicological
      tools for nematodes, ranging from molecular laboratory methods to experimental
      model ecosystem approaches, and their role as indicator organisms is given. The
      reviewed studies, approaches that range from species-based to community-based
      methods, reveal exciting possibilities for the future use of nematodes in
      ecotoxicological studies. Suitable ecotoxicological tools and ecological indices
      for nematodes should be integrated in weight-of-evidence approaches for assessing
      the ecological risk of contamination. 

PMID- 25861116
TI  - Descriptions of Deladenus albizicus n. sp. and D. processus n. sp. (Nematoda:
      Hexatylina) from Haryana, India.
AB  - Two different nematodes were isolated from the bark of Albizia lebbeck trees; one
      from insect infested and another from noninfested, healthy tree. Based on the
      biological, morphological, and molecular evidences, the nematodes are described
      as Deladenus albizicus n. sp. and D. processus n. sp. (Nematoda: Hexatylina).
      Deladenus albizicus n. sp., isolated from insect-infested tree, multiplied on the
      fungus Nigrospora oryzae. Myceliophagous females of this nematode reproduced by
      parthenogenesis and spermathecae were indistinct. Infective females, readily
      produced in the cultures, are dorsally curved. Only one type of males containing
      small-sized sperms in their genital tracts were produced in the culture.
      Myceliophagous females: L = 0.75 to 1.71 mm, a = 32.3 to 50.8, b = 9.3 to 11.2,
      b' = 5.2 to 7.3, c = 27.2 to 35.6, V = 91.0 to 93.3, c' = 2.0 to 2.9, stylet = 11
      to 12 um, excretory pore in the region of median pharyngeal bulb, 43 to 47 um
      anterior to hemizonid. Deladenus processus n. sp., isolated from bark of healthy
      A. lebbeck tree, was cultured on Alternaria alternata. Myceliophagous females
      reproduced by amphimixis and their spermathecae contained rounded sperms.
      Infective females were never produced, even in old cultures. Myceliophagous
      females: L = 0.76 to 0.99 mm, a = 34 to 49, b = 13.3 to 17.7, b' = 3.8 to 5.8, c
      = 19.6 to 22.8, V = 92.2 to 93.5, c' = 2.7 to 3.5, stylet = 6 to 7 um, excretory
      pore in the proximity of hemizonid, tail conoid, tapering from both sides to a
      long pointed central process. It is proposed to classify Deladenus species in
      three groups: durus, siricidicola, and laricis groups based on female and
      spermatogonia dimorphism, mode of reproduction, and insect parasitism. 

PMID- 25861117
TI  - Pathogenicity of Two Species of Entomopathogenic Nematodes Against the Greenhouse
      Whitefly, Trialeurodes vaporariorum (Hemiptera: Aleyrodidae), in Laboratory and
      Greenhouse Experiments.
AB  - The greenhouse whitefly Trialeurodes vaporariorum (Hemiptera: Aleyrodidae) is a
      polyphagous pest in greenhouse crops. The efficacy of two entomopathogenic
      nematodes (EPN), Steinernema feltiae and Heterorhabditis bacteriophora, as
      biological control agents against T. vaporariorum was evaluated using two model
      crops typical of vegetable greenhouse productions: cucumber and pepper.
      Laboratory tests evaluated adults and second nymphal instars for pest
      susceptibility to different EPN species at different concentrations of infective
      juveniles (IJ; 0, 25, 50, 100, 150, 200, and 250 IJ per cm(2)); subsequent
      greenhouse trials against second nymphal instars on cucumber and pepper plants
      evaluated more natural conditions. Concentrations were applied in combination
      with Triton X-100 (0.1% v/v), an adjuvant for increasing nematode activity. In
      laboratory studies, both life stages were susceptible to infection by the two
      nematode species, but S. feltiae recorded a lower LC50 than H. bacteriophora for
      both insect stages. Similarly, in greenhouse experiments, S. feltiae required
      lower concentrations of IJ than H. bacteriophora to reach the same mortality in
      nymphs. In greenhouse trials, a significant difference was observed in the triple
      interaction among nematode species * concentration * plant. Furthermore, the
      highest mortality rate of the second nymphal instars of the T. vaporariorum was
      obtained from the application of S. feltiae concentrated to 250 IJ/cm(2) on
      cucumber (49 +/- 1.23%). The general mortality caused by nematodes was
      significantly higher in cucumber than in pepper. These promising results support
      further investigation for the optimization of the best EPN species/concentration
      in combination with insecticides or adjuvants to reach a profitable control of
      this greenhouse pest. 

PMID- 25861118
TI  - Margollus bokanicus n. sp. from Iran, the Fourth Species of a Rare Nematode Genus
      (Dorylaimida, Tylencholaimellidae).
AB  - Margollus bokanicus n. sp., collected from natural habitats in Khorasaneh
      district, Bokan, West Azarbaijan province, Iran, is described. Morphological and
      morphometric data are provided as well as drawings and light microscopy
      illustrations. The new species is characterized by a medium size body length
      (0.60 to 0.73 mm), labial and postlabial sclerotizations, lip region 7-MUm wide,
      offset by constriction and long neck (167 to 207 MUm), long pharyngeal basal bulb
      (27 to 36 MUm) or 16% to 17% of total neck length, female genital system
      monodelphic-opisthodelphic, anterior branch reduced to a uterine sac (26-29 MUm)
      or 1.1 to 1.3 times the body diameter, long posterior uterus (25-28 MUm) or 1.1
      to 1.3 times the body diameter, V = 40 to 47, cylindroid female tail (17 to 24
      MUm, c = 31 to 38, c' = 1.1 to 1.4), and males unknown. This taxon is easily
      distinguishable from other Margollus species by its smaller general size and more
      posterior vulva. A compendium of Margollus species is also presented. 

PMID- 25861119
TI  - Broad Meloidogyne Resistance in Potato Based on RNA Interference of Effector Gene
      16D10.
AB  - Root-knot nematodes (Meloidogyne spp.) are a significant problem in potato
      (Solanum tuberosum) production. There is no potato cultivar with Meloidogyne
      resistance, even though resistance genes have been identified in wild potato
      species and were introgressed into breeding lines. The objectives of this study
      were to generate stable transgenic potato lines in a cv. Russet Burbank
      background that carry an RNA interference (RNAi) transgene capable of silencing
      the 16D10 Meloidogyne effector gene, and test for resistance against some of the
      most important root-knot nematode species affecting potato, i.e., M. arenaria, M.
      chitwoodi, M. hapla, M. incognita, and M. javanica. At 35 days after inoculation
      (DAI), the number of egg masses per plant was significantly reduced by 65% to 97%
      (P < 0.05) in the RNAi line compared to wild type and empty vector controls. The
      largest reduction was observed in M. hapla, whereas the smallest reduction
      occurred in M. javanica. Likewise, the number of eggs per plant was significantly
      reduced by 66% to 87% in M. arenaria and M. hapla, respectively, compared to wild
      type and empty vector controls (P < 0.05). Plant-mediated RNAi silencing of the
      16D10 effector gene resulted in significant resistance against all of the root
      knot nematode species tested, whereas R Mc1(blb) , the only known Meloidogyne
      resistance gene in potato, did not have a broad resistance effect. Silencing of
      16D10 did not interfere with the attraction of M. incognita second-stage
      juveniles to roots, nor did it reduce root invasion. 

PMID- 25861120
TI  - Suitability of Zucchini and Cucumber Genotypes to Populations of Meloidogyne
      arenaria, M. incognita, and M. javanica.
AB  - The host suitability of five zucchini and three cucumber genotypes to Meloidogyne
      incognita (MiPM26) and M. javanica (Mj05) was determined in pot experiments in a
      greenhouse. The number of egg masses (EM) did not differ among the genotypes of
      zucchini or cucumber, but the eggs/plant and reproduction factor (Rf) did
      slightly. M. incognita MiPM26 showed lower EM, eggs/plant, and Rf than M.
      javanica Mj05. Examination of the zucchini galls for nematode postinfection
      development revealed unsuitable conditions for M. incognita MiPM26 as only 22% of
      the females produced EM compared to 95% of the M. javanica females. As far as
      cucumber was concerned, 86% of the M. incognita and 99% of the M. javanica
      females produced EM, respectively. In a second type of experiments, several
      populations of M. arenaria, M. incognita, and M. javanica were tested on zucchini
      cv. Amalthee and cucumber cv. Dasher II to assess the parasitic variation among
      species and populations of Meloidogyne. A greater parasitic variation was
      observed in zucchini than cucumber. Zucchini responded as a poor host for M.
      incognita MiPM26, MiAL09, and MiAL48, but as a good host for MiAL10 and MiAL15.
      Intraspecific variation was not observed among the M. javanica or M. arenaria
      populations. Cucumber was a good host for all the tested populations. Overall,
      both cucurbits were suitable hosts for Meloidogyne but zucchini was a poorer host
      than the cucumber. 

PMID- 25861121
TI  - First Report of Northern Root-Knot Nematode, Meloidogyne hapla, Parasitic on
      Oaks, Quercus brantii and Q. infectoria in Iran.
AB  - Root-knot nematodes (RKN) are the most serious plant parasitic nematodes having a
      broad host range exceeding 2,000 plant species. Quercus brantii Lindl. and Q.
      infectoria Oliv are the most important woody species of Zagros forests in west of
      Iran where favors sub-Mediterranean climate. National Botanical Garden of Iran
      (NBGI) is scheduled to be the basic center for research and education of botany
      in Iran. This garden, located in west of Tehran, was established in 1968 with an
      area of about 150 ha at altitude of 1,320 m. The Zagros collection has about 3-ha
      area and it has been designed for showing a small pattern of natural Zagros
      forests in west of Iran. Brant's oak (Q. brantii) and oak manna tree (Q.
      infectoria) are the main woody species in Zagros collection, which have been
      planted in 1989. A nematological survey on Zagros forest collection in NBGI
      revealed heavily infection of 24-yr-old Q. brantii and Q. infectoria to RKN,
      Meloidogyne hapla. The roots contained prominent galls along with egg sac on the
      surface of each gall. The galls were relatively small and in some parts of root
      several galls were conjugated, and all galls contained large transparent egg
      masses. The identification of M. hapla was confirmed by morphological and
      morphometric characters and amplification of D2-D3 expansion segments of 28S rRNA
      gene. The obtained sequences of large-subunit rRNA gene from M. hapla was
      submitted to the GenBank database under the accession number KP319025. The
      sequence was compared with those of M. hapla deposited in GenBank using the BLAST
      homology search program and showed 99% similarity with those KJ755183, GQ130139,
      DQ328685, and KJ645428. The second stage juveniles of M. hapla isolated from
      Brant's oak (Q. Brantii) showed the following morphometric characters: (n = 12),
      L = 394 +/- 39.3 (348 to 450) um; a = 30.9 +/- 4 (24.4 to 37.6); b = 4.6 +/- 0.44
      (4 to 5.1); b? = 3.3 +/- 0.3 (2.7 to 3.7), c = 8.0 +/- 1 (6.2 to 10.3), c = 5.3
      +/- 0.8 (3.5 to 6.3); Stylet = 12.1 +/- 0.8 (11 to 13) um; Tail = 50 +/- 5.6 (42
      to 57) um; Hyaline 15 +/- 1.8 (12 to 18) um. Oak manna, Q. infectoria population
      of second stage juveniles clearly possessed short body length and consequently
      other morphometric features were less than those determined for Q. brantii
      population, and these features were: (n = 12), L = 359.0 +/- 17.3 (319 to 372)
      um; a = 28.6 +/- 3 (22.8 to 31); b = 5.0 +/- 0.3 (4.8 to 5.2); b? = 3.3 +/- 0.2
      (3 to 3.6), c = 8.1 +/- 0.5 (7.4 to 8.8), c = 4.7 +/- 0.5 (3.9 to 5.2); Stylet =
      11.4 +/- 0.7 (10 to 12) um; Tail = 44 +/- 1.8 (42 to 47) um; Hyaline 12 +/- 1.7
      (10 to 15) um. To date two species of Meloidogyne, M. quercianaGolden, 1979 and
      M. christieiGolden and Kaplan, 1986 have been reported to parasitize oaks
      (Quercus spp.) from the United States of America. M. querciana was found on pin
      oak Quercus palustris in Virginia. The oak RKN infected pine oak, red oak, and
      American chestnut heavily in greenhouse tests (Golden, 1979). The other species
      M. christiei was described from turkey oak and Q. laevis in Florida, which has
      monospecific host range (Golden and Kaplan, 1986). Both of these RKN species seem
      to be restricted to the United States of America and have not been reported from
      other place. According to our knowledge this is the first report of occurrence of
      M. hapla on Q. brantii and Q. infectoria in the world. This study includes these
      two oak species to the host range of RKN, M. hapla for the world and expands the
      information of RKN, M. hapla host ranges on oaks. 

PMID- 25861122
TI  - Gonadal Restructuring During Sex Transition in California Sheephead: a
      Reclassification Three Decades After Initial Studies.
AB  - California Sheephead, Semicossyphus pulcher, is a monandric protogynous
      hermaphrodite and a commercially and recreationally valuable labrid. Gonadal
      functionality of Sheephead through sex change was reclassified into nine classes
      using current criteria for categorization. Female ovaries were classified as
      immature, early maturing, mature, and regressing/recovering classes. Transition
      from female to male and subsequent male development was divided into early, mid
      and late transitional, developing/active male and regressing/recovering male.
      Reproductive states in Sheephead were correlated with estradiol (E2) and 11-keto
      testosterone (11-KT) concentrations in the blood plasma. All sexes had low E2
      concentrations in the fall /winter seasons; in transitional and male individuals,
      levels remained low throughout the year. In contrast, female E2 concentrations
      were elevated in spring and peaked in the summer. Concentrations of 11-KT were
      variable throughout the year; however, females had significantly lower levels in
      the summer. This study allows a better understanding of the current state of
      California Sheephead in a heavily fished area. Knowledge of a species'
      reproductive characteristics is important in evaluating the sustainability of a
      population as it can set a baseline for reproductive potential. This research
      takes a critical step in gathering and organizing reproductive data such that it
      may be used in future studies for comparing reproductive potential across the
      range of the California sheephead.

PMID- 25861123
TI  - Palladium-Catalyzed Ligand-Directed Oxidative Functionalization of Cyclopropanes.
AB  - This report describes the Pd-catalyzed functionalization of cyclopropanes
      containing oxazoline, oxime ether, and pyridine directing groups. Three different
      oxidants were examined in these studies: IOAc, PhI(OAc)2, and benzoquinone. The
      reactions yielded products derived from 2 degrees  sp3 C-H functionalization
      and/or C-C activation of the cyclopropane ring. The outcome and the product
      distributions were highly dependent on the structure of the substrate and the
      nature of the oxidant.

PMID- 25861124
TI  - Roles of Oxidized Diacylglycerol for Carbon Tetrachloride-induced Liver Injury
      and Fibrosis in Mouse.
AB  - Since there is a report that an inhibitor of protein kinase C (PKC) effectively
      suppresses the development of hepatic fibrosis, it is suggested that the PKC
      signaling pathway plays an important role in the pathogenesis of hepatic
      fibrosis. We reported that oxidized diacylglycerol (DAG), which is an activator
      of PKC, had a remarkably stronger PKC-activating action than un-oxidized DAG. In
      the present study, we explored the roles of oxidized DAG in hepatic fibrogenesis
      using mice, the livers of which developed fibrosis by long-term administration of
      carbon tetrachloride (CCl4). Liver fibrosis models were created by 4- or 8-week
      repetitive subcutaneous injections of CCl4 to the backs of C57BL/6J mice. The
      amount of oxidized DAG was significantly increased in the CCl4-treated group.
      Moreover, it was found that PKCalpha, betaI, betaII and delta were activated. In
      the CCl4-treated group, phosphorylation of ERK and JNK, which are downstream
      signal transmitters in the PKC pathway, was increased. It was also found in this
      group that there was an increase in TIMP-1, which is a fibrogenesis-promoting
      factor whose expression is enhanced by activated JNK, and of TNF-alpha, an
      inflammatory cytokine. Analysis by quantitative real-time RT-PCR showed that
      expressions of alphaSMA, collagen I, TNF-alpha and IL-10 were remarkably
      increased in the 8-week CCl4-treated group. The above results strongly suggested
      that oxidized DAG, which is increased by augmented oxidative stress, activated
      PKCalpha, betaI, betaII and delta molecular species and that these molecular
      species in turn stimulated the phosphorylation of MAP kinases including ERK and
      JNK, resulting in enhancement of hepatic fibrogenesis. 

PMID- 25861125
TI  - Re-epithelialization of the Buccal Mucosa after Alkaline Chemical Injury.
AB  - Alkaline conditions in the oral cavity may be caused by a variety of stimuli,
      including tobacco products, antacids, alkaline drinking water and bicarbonate
      toothpaste. However, the effects of an alkaline pH on the oral mucosa had not
      been elucidated. The purpose of this study was to investigate how basal
      keratinocytes are actively involved in re-epithelialization after alkaline
      chemical injury. We generated epithelial defects in the oral mucosa of mice by
      applying an alkaline chemical, and the localization of cytokeratin 13,
      cytokeratin 14, PCNA and p63 was investigated during the re-epithelialization
      process. PCNA- and p63-positive staining was seen in basal cells covering the
      wound surface at 1 day after the chemical injury. Cytokeratin 14-positive and
      PCNA-negative basal keratinocytes were localized in a few layers of the wound
      epithelium during epithelial outgrowth. Cytokeratin 14-positive and PCNA-positive
      basal keratinocytes, indicating proliferation, were localized over the entire
      layer of the epithelium at the wound margin. These results imply that basal
      keratinocytes at the wound margin migrate to the wound surface, provoke
      differentiation and keratinization during epithelial outgrowth and that
      epithelial cells are supplied from the wound margin to the epithelial outgrowth
      after alkaline chemical injury. 

PMID- 25861126
TI  - Stimulation of melanogenesis by nordihydroguaiaretic Acid in human melanoma
      cells.
AB  - Nordihydroguaiaretic acid (NDGA), a lignan found in vegetables, fruits and
      legumin, has been shown to possess antineoplastic, antiviral and antioxidant
      characteristics. In this study, we examined the effect of NDGA on melanogenesis
      in human melanoma cells (HMVII). In vitro, NDGA does not alter mushroom
      tyrosinase activity. However, in NDGA-treated HMVII cells, cellular tyrosinase
      activity increased in both a time- and dose-dependent manner. The concomitant
      increases in melanin content in NDGA-treated cells indicated an elevation of
      melanin synthesis by tyrosinase activation. In addition, after a 7-day
      incubation, melanin content in 20 MUM NDGA-treated cells increased 5.02 fold.
      Tyrosinase protein also increased by treatment with NDGA. Nevertheless,
      tyrosinase mRNA was not altered in NDGA-treated cells. Our results suggest that
      NDGA can increase tyrosinase activity and de novo synthesis of melanin in human
      melanoma cells. We found that NDGA is a novel potent stimulator of melanogenesis
      in human melanoma cells. 

PMID- 25861127
TI  - Pathogenesis of focal cytoplasmic necrosis of the smooth muscle cells in
      hypertensive rat arterial media.
AB  - Hypertensive rat arteries exhibited severe medial smooth muscle cell injury and
      necrosis. Electron microscopic observations showed the smooth muscle cells of
      these arteries exhibited characteristics of focal cytoplasmic necrosis forming
      new cytodemarcating membrane between the healthy cytoplasm and necrotic
      cytoplasm. When the focal necrotic cytoplasm disappeared from the injured smooth
      muscle cells, it left it with a moth-eaten leaf-like appearance (moth-eaten
      necrosis). At an advanced stage of injury, smooth muscle cells changed to islet
      like cell bodies with newly formed basement membranes around them, and further
      islet-like cell bodies and cell debris disappeared leaving lamellar and reticular
      basement membranes. In hypertensive rats injected with nitroblue tetrazolium
      (NBT), formazan deposits were observed in the medial cells and nitrotyrosine, a
      biomarker of peroxynitrite, were immunohistochemically observed in the arterial
      media. Nick-end positive extranuclear small granular bodies, which might have
      derived from focal necrotic cytoplasm and nucleus, were detected in the arterial
      media using DNA nick-end labeling method. Based on electron microscopical and
      histochemical findings, we conjectured that the focal cytoplasmic necrosis of the
      smooth muscle cells in the arterial media depended on injury arising from
      mitochondria-derived oxidants. 

PMID- 25861128
TI  - Expressions of Somatostatin Receptor Subtypes (SSTR-1, 2, 3, 4 and 5) in
      Neuroblastic Tumors; Special Reference to Clinicopathological Correlations with
      International Neuroblastoma Pathology Classification and Outcomes.
AB  - Somatostatin receptor (SSTR) expressions in neuroblastomas (NBs) have been
      confirmed employing various methods. High SSTR-2 expression was suggested to be a
      favorable prognostic marker, though little is known about the relationships
      between the expressions of SSTR subtypes, other than SSTR-2, and prognosis. We
      investigated the expressions of all five known SSTR subtypes in 63 neuroblastic
      tumors (NTs), employing immunohistochemistry, and also conducted quantitative
      real-time RT-PCR in 37 of these tumors. We evaluated correlations between the
      expressions of SSTR subtypes and prognosis, based on the International
      Neuroblastoma Pathology Classification and patient outcomes. More than 90% of
      cases expressed, at a minimum, SSTR-1 and/or 2. Ganglioneuromas and
      ganglioneuroblastomas expressed more than two SSTR subtypes. Among NBs, the
      favorable histology group showed higher SSTR subtype expressions than the
      unfavorable histology group. The same tendency was observed when surviving and
      deceased cases were compared, though SSTR-2 expression was well preserved in some
      of the deceased cases. In conclusion, NTs highly expressed SSTR-1 and/or 2, and
      expressions of SSTR generally indicate a good prognosis. However, even those in
      the unfavorable histology group with NBs expressing SSTR are good candidates for
      molecular targeting therapy using somatostatin analogues. 

PMID- 25861129
TI  - Changes in laminin chain expression in pre- and postnatal rat pituitary gland.
AB  - Cell-matrix interaction is required for tissue development. Laminin, a major
      constituent of the basement membrane, is important for structural support and as
      a ligand in tissue development. Laminin has 19 isoforms, which are determined by
      combinational assembly of five alpha, three beta, and three gamma chains (eg,
      laminin 121 is alpha1, beta2, and gamma1). However, no report has identified the
      laminin isoforms expressed during pituitary development. We used in situ
      hybridization to investigate all laminin chains expressed during rat anterior
      pituitary development. The alpha5 chain was expressed during early pituitary
      development (embryonic day 12.5-15.5). Expression of alpha1 and alpha4 chains was
      noted in vasculature cells at embryonic day 19.5, but later diminished. The
      alpha1 chain was re-expressed in parenchymal cells of anterior lobe from
      postnatal day 10 (P10), while the alpha4 chain was present in vasculature cells
      from P30. The alpha2 and alpha3 chains were transiently expressed in vasculature
      cells and anterior lobe, respectively, only at P30. Widespread distribution of
      beta and gamma chains was also observed during development. These findings
      suggest that numerous laminin isoforms are involved in anterior pituitary gland
      development and that alteration of the expression pattern is required for proper
      development of the gland. 

PMID- 25861130
TI  - Folliculostellate cells are required for laminin release from gonadotrophs in rat
      anterior pituitary.
AB  - The anterior pituitary gland is organized tissue comprising hormone-producing
      cells and folliculostellate (FS) cells. FS cells interconnect to form a meshwork,
      and their cytoplasmic processes are anchored by a basement membrane containing
      laminin. Recently, we developed a three-dimensional (3D) cell culture that
      reproduces this FS cell architecture. In this study of the novel function of FS
      cells, we used transgenic rats that express green fluorescent protein in FS cells
      for the 3D culture. Anterior pituitary cells were cultured with different
      proportions of FS cells (0%, 5%, 10%, and 20%). Anterior pituitary cells
      containing 5-20% FS cells formed round/oval cell aggregates, whereas amorphous
      cell aggregates were formed in the absence of FS cells. Interestingly,
      immunohistochemistry showed laminin-immunopositive cells instead of extracellular
      laminin deposition in FS cell-deficient cell aggregates. Double-immunostaining
      revealed that these laminin-immunopositive cells were gonadotrophs. Laminin mRNA
      expression did not differ in relation to the presence or absence of FS cells.
      When anterior pituitary cells with no FS cells were cultured with FS cell
      conditioned medium, the proportion of laminin-immunopositive cells was lower than
      in control. These results suggest that a humoral factor from FS cells is required
      for laminin release from gonadotrophs. 

PMID- 25861131
TI  - In Vivo Detection of Rat Colorectal Cancers by using a Dual-Wavelength Excitation
      Method.
AB  - Hypoxia is a characteristic feature of solid neoplasms, and insufficient oxygen
      supply increases cellular nicotinamide adenine dinucleotide (NADH) fluorescence,
      which is a main component of autofluorescence of the colorectal mucosa. We
      investigated whether a dual-wavelength excitation method which is optimized for
      sensing mucosal NADH fluorescence could be applicable to the detection of rat
      colorectal cancers in vivo. Rat colorectal adenocarcinomas were studied by using
      fluorescence stereomicroscopy. After autofluorescence images at 470 nm irradiated
      with dual-wavelength excitation at 365 nm (F365 ex) and 405 nm (F405 ex) were
      acquired, ratio images were produced by dividing F365 ex by F405 ex: The
      excitation-emission wavelength pairs in F365 ex and F405 ex were adjusted for
      acquisition of NADH fluorescence and reference fluorescence. Based on
      observations from the luminal surface in vivo, F365 ex/F405 ex ratio images
      indicated a 1.57-fold higher signal value in the cancers than in the surrounding
      normal mucosa. The signal values in F365 ex/F405 ex ratio images were less
      mutually related with the hemoglobin concentration index. Small adenocarcinomas
      (less than 4 mm) could be detected on F365 ex/F405 ex ratio images. The results
      showed that NADH fluorescence measurement with little interference from tissue
      hemoglobin is efficient for visualizing rat colorectal cancers in vivo,
      suggesting that the dual-wavelength excitation method has potential for label
      free endoscopic detection of diminutive colorectal neoplasms. 

PMID- 25861132
TI  - How Does the Ca(2+)-paradox Injury Induce Contracture in the Heart?-A Combined
      Study of the Intracellular Ca(2+) Dynamics and Cell Structures in Perfused Rat
      Hearts.
AB  - The calcium (Ca(2+))-paradox injury of the heart, induced by restoration of
      extracellular Ca(2+) after its short-term depletion, is known to provoke
      cardiomyocyte contracture. However, undetermined is how the Ca(2+)-paradox
      provokes such a distinctive presentation of myocytes in the heart. To address
      this, we imaged sequential intracellular Ca(2+) dynamics and concomitant
      structures of the subepicardial ventricular myocytes in fluo3-loaded, Langendorff
      perfused rat hearts produced by the Ca(2+) paradox. Under rapid-scanning confocal
      microscopy, repletion of Ca(2+) following its depletion produced high-frequency
      Ca(2+) waves in individual myocytes with asynchronous localized contractions,
      resulting in contracture within 10 min. Such alterations of myocytes were
      attenuated by 5-mM NiCl2, but not by verapamil, SEA0400, or combination of
      ryanodine and thapsigargin, indicating a contribution of non-specific
      transmembrane Ca(2+) influx in the injury. However, saponin-induced membrane
      permeabilization of Ca(2+) showed no apparent contracture despite the emergence
      of high-frequency Ca(2+) waves, indicating an essential role of myocyte-myocyte
      and myocyte-extracellular matrix (ECM) mechanical connections in the Ca(2+)
      paradox. In immunohistochemistry Ca(2+) depletion produced separation of the
      intercalated disc that expresses cadherin and dissipation of beta-dystroglycan
      located along the sarcolemma. Taken together, along with the trans-sarcolemmal
      Ca(2+) influx, disruption of cell-cell and cell-ECM connections is essential for
      contracture in the Ca(2+)-paradox injury. 

PMID- 25861133
TI  - New Grocott Stain without Using Chromic Acid.
AB  - We established a new "ecological" Grocott stain for demonstrating fungi, based
      upon a 4R principle of refusal, reduction, reuse, and recycle of waste
      management. Conventional Grocott stain employs environmentally harsh 5% chromic
      acid for oxidization. Initially, we succeeded in reducing the concentration of
      chromic acid from 5% to 1% by incubating the solution at 60 degrees C and using
      five-fold diluted chromic acid solution at which point it was reusable.
      Eventually, we reached the refusal level where 1% periodic acid oxidization was
      efficient enough, when combined with preheating of sections in the electric jar,
      microwave oven, or pressure pan. For convenience sake, we recommend pressure pan
      heating in tap water for 10 min. Stainability of fungi in candidiasis and
      aspergillosis was comparable with conventional Grocott stain, while Mucor hyphae
      showed enhanced staining. The modified sequence was further applicable to
      detecting a variety of mycotic pathogens in paraffin sections. Our
      environmentally-friendly Grocott stain also has the advantage of avoiding risk of
      human exposure to hexavalent chromium solution in the histopathology laboratory.
      The simple stain sequence is can be easily applied worldwide. 

PMID- 25861134
TI  - Immunohistochemical Analysis of Collagen IV and Laminin Expression in Spontaneous
      Melanoma Regression in the Melanoma-Bearing Libechov Minipig.
AB  - Spontaneous regression (SR) of human melanoma is a rare, well-documented
      phenomenon that is not still fully understood. Its detailed study cannot be
      performed in patients due to ethical reasons. Using the Melanoma-bearing Libechov
      Minipig (MeLiM) animals of various ages (from 3 weeks to 8 months) we implemented
      a long-term monitoring of melanoma growth and SR. We focused on
      immunohistochemical detection of two important extracellular matrix proteins,
      collagen IV and laminin, which are associated with cancer. We showed that SR of
      melanoma is a highly dynamic process. The expression of collagen IV and laminin
      correlated with changes in population of melanoma cells. Tumours of 3-week-old
      animals consisted primarily of melanoma cells with a granular expression of
      collagen IV and laminin around them. Thereafter, melanoma cells were gradually
      destroyed and tumour tissue was rebuilt into the connective tissue. Collagen IV
      expression slightly increased in tumours of 10-week-old pigs showing
      extracellular fibrous appearance. In tumours of older animals, areas lacking
      melanoma cells demonstrated a low expression and areas still containing melanoma
      cells a high expression of both proteins. We considered the age of 10 weeks as a
      turning point in the transition between tumour growth and SR of the MeLiM
      melanoma. 

PMID- 25861135
TI  - ACUTE MENTAL STRESS AND HEMOSTASIS: WHEN PHYSIOLOGY BECOMES VASCULAR HARM.
AB  - Stress-induced activation of the sympathoadrenal medullary system activates both
      the coagulation and fibrinolysis system resulting in net hypercoagulability. The
      evolutionary interpretation of this physiology is that stress-hypercoagulability
      protects a healthy organism from excess bleeding should injury occur in fight-or
      flight situations. In turn, acute mental stress, negative emotions and
      psychological trauma also are triggering factors of atherothrombotic events and
      possibly of venous thromboembolism. Individuals with pre-existent atherosclerosis
      and impaired endothelial anticoagulant function are the most vulnerable to
      experience onset of acute coronary events within two hours of intense emotions. A
      range of sociodemographic and psychosocial factors (e.g., chronic stress and
      negative affect) might critically intensify and prolong stress-induced
      hypercoagulability. In contrast, several pharmacological compounds, dietary
      flavanoids, and positive affect mitigate the acute prothrombotic stress response.
      Studies are needed to investigate whether attenuation of stress
      hypercoagulability through medications and biobehavioral interventions reduce the
      risk of thrombotic incidents in at-risk populations.

PMID- 25861136
TI  - Rapid screening of heavy metals and trace elements in environmental samples using
      portable X-ray fluorescence spectrometer, A comparative study.
AB  - With industrialization, great amounts of trace elements and heavy metals have
      been excavated and released on the surface of the earth and dissipated into the
      environments. Rapid screening technology for detecting major and trace elements
      as well as heavy metals in variety of environmental samples is most desired. The
      objectives of this study were to determine the detection limits, accuracy,
      repeatability and efficiency of a X-ray fluorescence spectrometer (Niton XRF
      analyzer) in comparison with the traditional analytical methods, inductively
      coupled plasma optical emission spectrometer (ICP-OES) and inductively coupled
      plasma optical emission spectrometer (ICP-MS) in screening of major and trace
      elements of environmental samples including estuary soils and sediments,
      contaminated soils, and biological samples. XRF is a fast and non-destructive
      method in measuring the total concentration of multi--elements simultaneously.
      Contrary to ICP-OES and ICP-MS, XRF analyzer is characterized by the limited
      preparation required for solid samples, non-destructive analysis, increased total
      speed and high throughout, the decreased production of hazardous waste and the
      low running costs as well as multi-elemental determination and portability in the
      fields. The current comparative study demonstrates that XRF is a good rapid non
      destructive method for contaminated soils, sediments and biological samples
      containing higher concentrations of major and trace elements. Unfortunately, XRF
      does not have sensitive detection limits of most major and trace elements as ICP
      OES or ICP-MS but it may serve as a rapid screening tool for locating hot spots
      of uncontaminated field soils and sediments.

PMID- 25861137
TI  - Research for understanding as opposed to evaluating Ayurveda.

PMID- 25861138
TI  - Analgesic and anti-inflammatory effects of aqueous extract of leaves of
      Pentatropis capensis Linn. f. (Bullock).
AB  - BACKGROUND: Herbal analgesic and anti-inflammatory remedies are preferred much
      because of lesser side effects and also a lower tendency for habit formation.
      Pentatropis capensis is such an analgesic and anti-inflammatory drug which is
      popular among folklore remedies for various injuries and inflammatory problems.
      It is called by the name of Kakanasika in Ayurvedic works. This study was
      designed to investigate the analgesic, and anti-inflammatory effects of aqueous
      extract of P. capensis leaves (AEPC) in rats. MATERIALS AND METHODS: AEPC was
      assessed for Analgesic effect through radiant heat tail-flick model and anti
      inflammatory effect through carrageenan-induced paw edema model on Wistar strain
      of albino rats. RESULTS: Pentatropis capensis leaves aqueous extract showed
      significant (P < 0.001) increase in the duration of latency of tail flick
      response at the dose levels of 450 mg/kg, p.o. as compared to the control group.
      Similarly, the similar dose level produced significant (P < 0.01) anti
      inflammatory effect against acute paw edema after 3 h of carrageenan induction
      when compared to the control group. CONCLUSION: The observed effects were
      comparable with the standard drug-treated group thus demonstrating effective
      central analgesic and acute anti-inflammatory potentials of the P. capensis
      leaves aqueous extract and the observations substantiate its folklore use as an
      analgesic and anti-inflammatory.

PMID- 25861139
TI  - Gamma amino butyric acid accumulation in medicinal plants without stress.
AB  - INTRODUCTION: Gamma amino butyric acid (GABA) is an important ubiquitous four
      carbon nonprotein amino acid with an amino group attached to gamma carbon instead
      of beta carbon. It exists in different organisms including bacteria, plants, and
      animals and plays a crucial role in humans by regulating neuronal excitability
      throughout the nervous system. It is directly responsible for the regulation of
      muscle tone and also effective in lowering stress, blood pressure, and
      hypertension. AIM AND OBJECTIVE: The aim of the study was to develop the
      fingerprint profile of selected medicinally and economically important plants
      having central nervous system (CNS) activity and to determine the quantity of
      GABA in the selected plants grown under natural conditions without any added
      stress. MATERIALS AND METHODS: The high-performance thin layer chromatography
      analysis was performed on precoated silica gel plate 60F-254 plate (20 cm * 10
      cm) in the form of bands with width 8 mm using Hamilton syringe (100 MUl) using n
      butanol, acetic acid, and water in the proportion 5:2:2 as mobile phase in a
      CAMAG chamber which was previously saturated for 30 min. CAMAG TLC scanner 3 was
      used for the densitometric scanning at 550 nm. Specific marker compounds were
      used for the quantification. RESULTS AND CONCLUSION: Among the screened medicinal
      plants, Zingiber officinale and Solanum torvum were found to have GABA. The
      percentage of GABA present in Z. officinale and S. torvum were found to be
      0.0114% and 0.0119%, respectively. The present work confirmed that among the
      selected CNS active medicinal plants, only two plants contain GABA. We found a
      negative correlation with plant having CNS activity and accumulation of GABA. The
      GABA shunt is a conserved pathway in eukaryotes and prokaryotes but, although the
      role of GABA as a neurotransmitter in mammals is clearly established, its role in
      plants is still vague.

PMID- 25861140
TI  - Anatomical investigation of flower of Butea monosperma Lam.
AB  - BACKGROUND: Butea frondosa Roxb. and Koen. syn. Butea monosperma Lam.
      (Leguminosae or Fabaceae) is a tree grows up to the height of 8 m at the age 50
      years. Its flowers are being used in traditional medicine for the treatment of
      ulcer, inflammation, hepatic disorder, and eye diseases. AIMS: The present study
      was aimed at establishing the microscopic characteristics of flower B. monosperma
      Lam. MATERIALS AND METHODS: Histological evaluation of flowers was done using
      standard procedures. Images of microscopic characters were taken at different
      magnifications using Nikon Labphoto 2 microscopic Unit. Perkin Elmer 5000 an
      atomic absorption spectrophotometer was employed for elemental analysis. RESULTS:
      In the study, microscopic characters of floral parts were investigated in
      transverse section and the flower powder. The current study reveals the presence
      of pollen grains, ovary (OV), and trichomes in their flower powder. Different
      cell components were studied, and their sizes were measured. Elemental analysis
      showed the presence of Zn 52.2 MUg/g and Cu 36.3 MUg/g were major contents,
      whereas Cr, Mn, and Pd were minor contents in dried flower powder. CONCLUSION:
      The current study paves the way to provide standard information related to the
      presence of essential elements in the flower. Microscopic characters of the
      flower and its quantitative measurement of cell components will help to identify
      the plant and also help to improvise the existing monograph of B. monosperma in
      the Ayurvedic pharmacopoeia.

PMID- 25861141
TI  - Phytochemical investigation of natural and in vitro raised Vrddhadaruka plants.
AB  - BACKGROUND: Argyreia nervosa commonly known as elephant creeper (English) and
      Vrddhadaruka (Sanskrit) is a woody climber that belongs to the family
      Convolvulaceae. Seeds of this plant contain hallucinogens including ergot
      alkaloids and a naturally occurring lysergic acid amide. Traditionally the plant
      is used in the treatment of gonorrhea, strangury, chronic ulcers, diabetes,
      anemia and cerebral disorders. The plant is also used as appetitiser, brain
      tonic, cardiotonic, aphrodisiac. It possesses anti-inflammatory,
      immunomodulatory, antibacterial, antiviral and antifungal activities. OBJECTIVE:
      To give an account of information on in vitro regeneration and phytochemical
      analysis of the plant. MATERIALS AND METHODS: Nodal explants were selected for in
      vitro regeneration. Different aerial parts viz., seeds, natural and in vitro
      leaf, stem and callus were dried and extracted with different solvents and were
      subjected to various phytochemical analyses. RESULTS: Different concentrations of
      6-benzylaminopurine showed shoot and root initiation. The study of phytochemical
      screening of different extracts showed the presence of bioactive substances like
      flavonoids, alkaloids, terpenoids, etc. CONCLUSION: The study will provide an
      efficient in vitro protocol for micropropagation as an alternative method to
      conserve the plant and shows the presence of some important secondary metabolites
      in the nature grown and in vitro raised plants which can be useful for treatment
      of various diseases.

PMID- 25861142
TI  - Efficacy of garlic extract and chlorhexidine mouthwash in reduction of oral
      salivary microorganisms, an in vitro study.
AB  - OBJECTIVES: To assess and compare the antimicrobial effect of garlic extract and
      chlorhexidine (CHX) mouthwash solution against oral salivary microorganisms.
      MATERIALS AND METHODS: Thirty six salivary samples were obtained in dry plastic
      vials. Collected saliva samples were centrifuged. Each vial was mixed completely
      on a shaker after which 1 ml of saliva was added to 9 ml of ethanol by a sterile
      pipette and mixed. A volume of 1 ml of garlic hydro-alcoholic extract and 1 ml of
      mouthwash was added to 1 ml each case specimen and was transferred to culture
      medium of Trypticase Soy Agar. Agar plates were incubated at 37 degrees C for 48
      h to allow for microbial growth. Microbial colonies were counted by independent
      interpreter to evaluate the result. STATISTICAL ANALYSIS: Data obtained were
      analyzed using one-way ANOVA test. P < 0.001 was considered statistically
      significant. RESULT: Result of the study shows that mean colony count of salivary
      microbial population was (1984 +/- 400) 1127 in saline group (negative control),
      (50 +/- 4) 27 in (0.12%) CHX group (positive control), (700 +/- 200) 469 in
      garlic extract (5%) group (case control). CONCLUSION: Mouthwash containing garlic
      extract can be used as an alternative to CHX mouthwash.

PMID- 25861144
TI  - Pharmacognostical evaluation of Citrus jambhiri Lush. fruit.
AB  - BACKGROUND: Citrus jambhiri Lush., commonly known as Jambira Nimbu in Sanskrit is
      medium to large indigenous tree with spreading habit, less spiny than lemon and
      belonging to the family Rutaceae. In Ayurveda, it is used in many pharmaceutical
      procedures of purification (Sodhana), calcination (Marana) etc., Though it is an
      important plant, till date, no pharmacognostical reports have been available on
      its fruit. MATERIALS AND METHODS: Study of fruit and its powder, histochemical
      tests and preliminary physicochemical investigations were done. RESULTS AND
      CONCLUSION: Results showed prismatic crystals of calcium oxalate, aerenchyma
      cells, oil globules, pitted vessels, scalariform vessels, juicy sac, etc.,
      Preliminary physicochemical analysis revealed loss on drying (1.1%), ash value
      (1.4%), alcohol soluble extract (28.6%), and water soluble extract (53.3%). These
      observations can be of use in future studies.

PMID- 25861143
TI  - Management of Ano-Rectal disorders by Ksarasutra: A clinical report.
AB  - BACKGROUND: Ano-rectal complaints are usually benign in origin. Most of the
      patients suffering with these disorders do not seek medical advice at an early
      stage due to embarrassment. It results in advancement of the disease and
      significant disturbance in the quality of life. Among the available treatment
      modalities of ano-rectal disorders (ARDs), Ksarasutra (medicated thread) appears
      to be the best in terms of relief and nonrecurrence. AIMS AND OBJECTIVES: The aim
      of this study is to provide evidence-based data about the practical application
      of Ksarasutra (medicated thread) in the management of ARDs. MATERIALS AND
      METHODS: An ano-rectal operation theatre was established in September 2012, in
      association with the Government Ayurvedic Speciality Clinic at District Hospital,
      Rajahmundry, Andhra Pradesh, to facilitate the AYUSH services in Allopathic
      Hospitals. Present report includes the details of ARDs treated by Ksarasutra
      (Medicated thread) method during 2012-2013. A total of 127 ano-rectal cases were
      operated, which included 44 cases of hemorrhoids, 40 cases of fistula-in-ano, 39
      cases of fissure-in-ano and three cases of peri-anal abscess. All the cases were
      analyzed as per the observations, subjective and objective parameters, and follow
      up was carried out for a period of 6 months. RESULTS: In the 127 ARDs treated, 45
      patients suffering from hemorrhoids, 36 patients got complete relief, marked
      relief observed in 4 patients, moderate relief observed in 5 patients. In fistula
      in-ano, out of 40 patients 29 patients got complete relief, marked relief was
      seen in 7 patients out of them 4 patients were referred to anti-tubercular
      treatment center, 4 patients left against medical advice. In fissure-in-ano-out
      of 39 patients, 32 patients got complete relief, 5 patients got marked relief,
      moderate relief observed in 2 patients. These results authenticate the
      effectiveness of Ksarasutra, no adverse effects or recurrence observed in any
      case. CONCLUSIONS: ARDs are efficiently treated by Ksarasutra technique with
      prompt symptomatic resolution and prevention of recurrence and complications.

PMID- 25861145
TI  - Development of a Nasya fitness form for clinical practice.
AB  - INTRODUCTION: Nasya karma is prime treatment modality for urdhvajatrugata vikara.
      Though classics clearly mention yogya (arha), ayogya (anarha) criteria for Nasya
      karma some complications were noticed while practicing. In KLEUS Shri BMK
      Ayurveda Hospital Belgaum, out of 2867 patients 58 (0.58%) cases reported various
      complications during and after Nasya karma in the year of 2011 even after taking
      utmost care in selection of patients as well as drugs. This gave rise to need to
      develop quick screening criteria to minimize errors. OBJECTIVE: To develop Nasya
      fitness form for clinical practice to further minimize unusual complications and
      thus obtain the maximum result. MATERIALS AND METHODS: Literature pertaining to
      Nasya karma, Nasa sarira with anatomy of nose, vasculature, innervation,
      examination of the nose and various anatomical pathologies were considered to
      develop the fitness form. RESULTS: On the basis of examination of external nose,
      nasal cavity, concha, nasopharynx and paranasal sinus by anterior and posterior
      rhinoscopic examination fitness form was developed. CONCLUSION: Present fitness
      format will not only help to assess the nasal pathologies, which are obstacles
      for drug delivery, but also will help to attain optimum results and avoid unusual
      complications.

PMID- 25861146
TI  - Gastroprotective activity of reconstituted red fruit pulp concentrate of
      Citrullus lanatus in rats.
AB  - AIM: This study was carried out to evaluate the gastroprotective potential of the
      aqueous fruit pulp concentrate of Citrullus lanatus citroides (CLC) on pyloric
      ligation and indomethacin-induced ulcer in Wistar albino rats. MATERIALS AND
      METHODS: In indomethacin-induced ulcer model, CLC was administered in the doses
      of 250 mg/kg, 500 mg/kg and 1000 mg/kg body weight orally, tds for 5 days. The
      antiulcer activity was determined via observing reduction in ulcer index whereas
      in the pyloric ligation model, the gastroprotective effect of CLC was assessed
      from the alteration in volume of gastric juice, pH, free and total acidity,
      protein concentration in gastric juice. Further lipid peroxide (LPO), and
      activities of enzymic antioxidants such as superoxide dismutase (SOD) and
      catalase (CAT) was also determined along with the levels of hexose, hexosamine,
      sialic acid, fucose in gastric mucosa. RESULTS: In both models, treatment with
      CLC caused a significant reduction in lesion index when compared to vehicle
      treated group, providing evidence for antiulcer capacity. In pyloric ligation
      model, pretreatment with CLC resulted in significant increase in pH, enzymic
      antioxidants, that is, SOD, CAT, with a significant decrease in volume of gastric
      juice, free and total acidity, protein concentration, acid output, and LPO levels
      respectively. The presence of the flavonoids and polyphenols may be responsible
      for the gastroprotective effect of CLC. CONCLUSIONS: The aqueous fruit pulp
      concentrate of CLC showed significant gastroprotective potential against pyloric
      ligation and indomethacin-induced ulceration in rats.

PMID- 25861147
TI  - Nootropic (medhya) effect of Bhavita Sankhapuspi tablets: A clinical appraisal.
AB  - BACKGROUND: Nootropic (medhya) potential of sankhapuspi (Convolvulus pluricaulis
      Choisy.) is reported in Ayurvedic literature and modern studies are now
      validating the same. In spite of plentiful preclinical researches already carried
      out during the past decades, only meager clinical efforts exploring its nootropic
      activity have been reported. Present clinical study is an attempt to evaluate the
      nootropic effect of Sankhapuspi tablets. AIMS AND OBJECTIVE: To evaluate the
      nootropic effect of sankhapuspi tablets prepared by three Bhavana (levigation) of
      its curna (powder) with its own Svarasa (fresh juice). MATERIALS AND METHODS:
      Thirty volunteers between the age 16 and 25 years participated in this single
      group pre-post study. Weschler's memory scale was adopted to collect data before
      (pre) and after (post) intervention period (2 months). Paired t-test was used for
      analyzing the data. RESULTS: In auditory immediate test and delayed test, 41.03%
      and 48% improvement was found which statistically highly significant (<0.001). In
      visual immediate and delayed test 32.5% and 44.87% improvement was found
      respectively, which shows highly significant result (<0.001). CONCLUSION: Results
      reveal that sankhapuspi tablet shown highly significant results in improving
      memory, especially in long term memory loss in younger age group.

PMID- 25861148
TI  - Phytochemical screening and antioxidant, antimitotic, and antiproliferative
      activities of Trichodesma indicum shoot.
AB  - BACKGROUND: Traditionally Trichodesma indicum has been used for its therapeutic
      effect in folk medicine that include anti-inflammatory, analgesic and anticancer
      properties. In this work, we validate the anticancer potential of the plant.
      AIMS: To screen the shoot extracts T. indicum for their antimitotic and
      antiproliferative activities. MATERIALS AND METHODS: The dried aerial parts of T.
      indicum were successively extracted with petroleum ether, successive chloroform
      extract (SCH), successive ethanol extract (SEE) and water. The plant extracts
      were subjected to study of in vitro antioxidant activity using 2,2'- diphenyl-1
      picrylhydrazyl, 2,2'- azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) radical
      inhibition systems. The extracts were also tested for their in vitro antimitotic
      activity in Allium cepa root and antiproliferative activity using the yeast model
      and five human cell lines (MCF-7, HOP-62, MOLT-4, HCT-15 and PRO). RESULT AND
      CONCLUSION: The mitotic index for SCH and SEE was found to be 12.01 +/- 1.34 and
      12.99 +/- 0.25 mg/mL, respectively. The IC50 value in the antiproliferative assay
      was found to be 30.14s-35.36 mg/mL for SCH and SEE respectively. Both SCH and SEE
      extracts showed significant antimitotic and antiproliferative activity when
      compared to the standard methothreaxate, vincreastine and adriamycin. Among the
      extracts, SEE showed strong inhibition against MCF-7 and MOLT-4 cell lines at
      concentration <30 MUg/mL. Phytochemical analysis of extracts indicated the
      presence of beta-sitosterol, gallic acid and catechin. Based on these results, it
      is concluded that T. indicum may be a good candidate for the treatment of a
      variety of cancer. Thus, its traditional use is validated.

PMID- 25861149
TI  - Ayurvedic education.

PMID- 25861150
TI  - Competency based education in Ayurveda: Need of the hour?

PMID- 25861151
TI  - Anti-acne activity of Darchini and Tukhm Khashkhash.

PMID- 25861152
TI  - Serum metabolites as potential biomarkers for diagnosis of knee osteoarthritis.
AB  - Knee osteoarthritis (OA) is a highly prevalent chronic degenerative joint disease
      that mainly affects the elderly population. The aim of this study was to
      investigate serum signature metabolites as potential biomarkers for early
      diagnosis of knee OA. Global serum metabolic profiles of 40 patients with knee OA
      and 20 healthy controls (HC) were analyzed by ultra-performance liquid
      chromatography coupled to mass spectrometry. An OA-specific metabolic profile was
      established that can clearly discriminate patients with OA from HCs. Fourteen
      metabolites that are involved in the metabolism of amino acids, purine, energy,
      glycolysis, fatty acids, and lipids were significantly altered in patients with
      OA compared to HCs. These metabolites could be potentially used as biomarkers for
      the diagnosis of knee OA. 

PMID- 25861153
TI  - Measurement of cytokines and adhesion molecules in the first 72 hours after
      severe trauma: association with severity and outcome.
AB  - INTRODUCTION: Severity and outcome assessments are crucial in trauma. Our aim was
      to describe the role of a group of cytokines (TNFalpha, IL-6, IL-10, and HMGB-1)
      and ICAM-1 as severity and outcome assessment tools and their kinetics in the
      first 72 h after severe trauma. MATERIALS AND METHODS: Authors designed a
      prospective cohort study of severe polytrauma patients (ISS > 15) in a level 1
      Trauma Centre. Cytokines and ICAM-1 levels and Th1/Th2 ratios were assessed at
      admission, 24, 48, and 72 h. SIRS, SIRS with hypoperfusion, and shock were
      identified. Outcomes considered were ICU admission, ARDS, MODS, and death.
      RESULTS: Ninety-nine patients were enrolled (median ISS: 29 and age 31). There
      was an early release of pro- and anti-inflammatory mediators with higher values
      at admission (except for ICAM-1). On admission, IL-6 was associated with ISS, IL
      10 with SIRS with hypoperfusion, and HMGB-1 with shock. Several cytokines were
      associated with outcomes, especially IL-6 and IL-10 at 72 h with MODS and death.
      Low TNFalpha/IL-10 and IL-6/IL-10 ratios at 24 and 72 h were associated with MODS
      and death. CONCLUSIONS: Pro- and anti-inflammatory responses occur simultaneously
      and earlier after injury. Cytokines may be useful for outcome assessment,
      especially IL-6 and IL-10. Low Th1/Th2 ratio at 24 to 72 h is associated with
      MODS and death.

PMID- 25861154
TI  - Procalcitonin improves the Glasgow Prognostic Score for outcome prediction in
      emergency patients with cancer: a cohort study.
AB  - The Glasgow Prognostic Score (GPS) is useful for predicting long-term mortality
      in cancer patients. Our aim was to validate the GPS in ED patients with different
      cancer-related urgency and investigate whether biomarkers would improve its
      accuracy. We followed consecutive medical patients presenting with a cancer
      related medical urgency to a tertiary care hospital in Switzerland. Upon
      admission, we measured procalcitonin (PCT), white blood cell count, urea, 25
      hydroxyvitamin D, corrected calcium, C-reactive protein, and albumin and
      calculated the GPS. Of 341 included patients (median age 68 years, 61% males), 81
      (23.8%) died within 30 days after admission. The GPS showed moderate prognostic
      accuracy (AUC 0.67) for mortality. Among the different biomarkers, PCT provided
      the highest prognostic accuracy (odds ratio 1.6 (95% confidence interval 1.3 to
      1.9), P < 0.001, AUC 0.69) and significantly improved the GPS to a combined AUC
      of 0.74 (P = 0.007). Considering all investigated biomarkers, the AUC increased
      to 0.76 (P < 0.001). The GPS performance was significantly improved by the
      addition of PCT and other biomarkers for risk stratification in ED cancer
      patients. The benefit of early risk stratification by the GPS in combination with
      biomarkers from different pathways should be investigated in further
      interventional trials. 

PMID- 25861155
TI  - Facebook use and depressive symptomatology: Investigating the role of neuroticism
      and extraversion in youth.
AB  - The popularity of social networking sites, such as Facebook, has increased
      rapidly over the past decade, especially among youth. Consequently, the impact of
      Facebook use on mental health problems (e.g., depressive symptomatology) has
      become a recent area of concern. Yet, evidence for such a link has been mixed and
      factors that contribute to heterogeneity of findings have not been identified. In
      this study, we examined whether the association between Facebook use and
      depressive symptoms is moderated by individual factors (i.e., personality and
      sex). To this end, we measured Facebook use, depressive symptoms, and personality
      domains (i.e., extroversion and neuroticism) among 237 young adults. No direct
      association was found between Facebook use and depressive symptoms. However, for
      females with high neuroticism, more frequent Facebook use was associated with
      lower depressive symptoms. Our findings suggest a complex relationship between
      Facebook use and depressive symptomatology that appears to vary by sex and
      personality. Facebook use may be protective against depressive symptoms for
      female users with high levels of neuroticism, while Facebook use may be unrelated
      to depressive symptoms among males.

PMID- 25861157
TI  - The neural correlates of spatial and object working memory in elderly and
      Parkinson's disease subjects.
AB  - This fMRI study deals with the neural correlates of spatial and objects working
      memory (SWM and OWM) in elderly subjects (ESs) and idiopathic Parkinson's disease
      (IPD). Normal aging and IPD can be associated with a WM decline. In IPD
      population, some studies reported similar SWM and OWM deficits; others reported a
      greater SWM than OWM impairment. In the present fMRI research, we investigated
      whether compensated IPD patients and elderly subjects with comparable performance
      during the execution of SWM and OWM tasks would present differences in WM-related
      brain activations. We found that the two groups recruited a prevalent left
      frontoparietal network when performing the SWM task and a bilateral network
      during OWM task execution. More specifically, the ESs showed bilateral frontal
      and subcortical activations in SWM, at difference with the IPD patients who
      showed a strict left lateralized network, consistent with frontostriatal
      degeneration in IPD. The overall brain activation in the IPD group was more
      extended as number of voxels with respect to ESs, suggesting underlying
      compensatory mechanisms. In conclusion, notwithstanding comparable WM
      performance, the two groups showed consistencies and differences in the WM
      activated networks. The latter underline the compensatory processes of normal
      typical and pathological aging. 

PMID- 25861156
TI  - Recent advances in methamphetamine neurotoxicity mechanisms and its molecular
      pathophysiology.
AB  - Methamphetamine (METH) is a sympathomimetic amine that belongs to phenethylamine
      and amphetamine class of psychoactive drugs, which are widely abused for their
      stimulant, euphoric, empathogenic, and hallucinogenic properties. Many of these
      effects result from acute increases in dopamine and serotonin neurotransmission.
      Subsequent to these acute effects, METH produces persistent damage to dopamine
      and serotonin release in nerve terminals, gliosis, and apoptosis. This review
      summarized the numerous interdependent mechanisms including excessive dopamine,
      ubiquitin-proteasome system dysfunction, protein nitration, endoplasmic reticulum
      stress, p53 expression, inflammatory molecular, D3 receptor, microtubule
      deacetylation, and HIV-1 Tat protein that have been demonstrated to contribute to
      this damage. In addition, the feasible therapeutic strategies according to recent
      studies were also summarized ranging from drug and protein to gene level. 

PMID- 25861158
TI  - The short-term effects of transcranial direct current stimulation on
      electroencephalography in children with autism: a randomized crossover controlled
      trial.
AB  - Abnormal synaptic maturation and connectivity are possible etiologies of autism.
      Previous studies showed significantly less alpha activity in autism than normal
      children. Therefore, we studied the effects of anodal tDCS on peak alpha
      frequency (PAF) related to autism treatment evaluation checklist (ATEC). Twenty
      male children with autism were randomly assigned in a crossover design to receive
      a single session of both active and sham tDCS stimulation (11 mA) over F3 (left
      dorsolateral prefrontal cortex). Pre- to postsession changes in a measure of
      cortical activity impacted by tDCS (PAF) and ATEC were compared between groups.
      We also examined the associations between pre- and postsession changes in the PAF
      and ATEC. The results show significant pre- to postsession improvements in two
      domains of ATEC (social and health/behavior domains) following active tDCS,
      relative to sham treatment. PAF also significantly increased at the stimulation
      site, and an increase in PAF was significantly associated with improvements in
      the two domains of ATEC impacted by tDCS. The findings suggest that a single
      session of anodal tDCS over the F3 may have clinical benefits in children with
      autism and that those benefits may be related to an increase in PAF.

PMID- 25861159
TI  - Loss of AMP-activated protein kinase induces mitochondrial dysfunction and
      proinflammatory response in unstimulated Abcd1-knockout mice mixed glial cells.
AB  - X-linked adrenoleukodystrophy (X-ALD) is caused by mutations and/or deletions in
      the ABCD1 gene. Similar mutations/deletions can give rise to variable phenotypes
      ranging from mild adrenomyeloneuropathy (AMN) to inflammatory fatal cerebral
      adrenoleukodystrophy (ALD) via unknown mechanisms. We recently reported the loss
      of the anti-inflammatory protein adenosine monophosphate activated protein kinase
      (AMPKalpha1) exclusively in ALD patient-derived cells. X-ALD mouse model (Abcd1
      knockout (KO) mice) mimics the human AMN phenotype and does not develop the
      cerebral inflammation characteristic of human ALD. In this study we document that
      AMPKalpha1 levels in vivo (in brain cortex and spinal cord) and in vitro in Abcd1
      KO mixed glial cells are similar to that of wild type mice. Deletion of
      AMPKalpha1 in the mixed glial cells of Abcd1-KO mice induced spontaneous
      mitochondrial dysfunction (lower oxygen consumption rate and ATP levels).
      Mitochondrial dysfunction in ALD patient-derived cells and in AMPKalpha1-deleted
      Abcd1-KO mice mixed glial cells was accompanied by lower levels of mitochondrial
      complex (1-V) subunits. More importantly, AMPKalpha1 deletion induced
      proinflammatory inducible nitric oxide synthase levels in the unstimulated Abcd1
      KO mice mixed glial cells. Taken together, this study provides novel direct
      evidence for a causal role for AMPK loss in the development of mitochondrial
      dysfunction and proinflammatory response in X-ALD. 

PMID- 25861160
TI  - Nitrooleic acid protects against cisplatin nephropathy: role of COX-2/mPGES
      1/PGE2 cascade.
AB  - Nitrooleic acid (OA-NO2) is an endogenous lipid product which has novel signaling
      properties, particularly the activation of peroxisome proliferator-activated
      receptors. The current study aimed to evaluate the protective effects of OA-NO2
      against cisplatin-induced kidney injury in mice. Mice were pretreated with OA-NO2
      for 48 h before cisplatin administration, and the cisplatin-caused nephrotoxicity
      was evaluated. After the cisplatin treatment (72 h), the vehicle-treated mice
      displayed renal dysfunction, as evidenced by the elevated plasma urea and
      creatinine, which was consistent with the histological damage, such as tubular
      necrosis, dilation, protein cast, and desquamation of epithelial cells. In
      contrast, the severity of the renal dysfunction and histological change were
      reduced in the OA-NO2 pretreated mice. The renal COX-2 and mPGES-1 mRNAs and
      their respective proteins expression, together with the renal PGE2 amounts, were
      induced by the cisplatin treatment, but their initiation was reduced by OA-NO2.
      Moreover, the circulating TNF-alpha, renal TNF-alpha, IL-1beta, MCP-1, ICAM-1,
      and VACAM-1 mRNA levels were higher in the cisplatin-treated mice, compared with
      the controls, but they were attenuated in the OA-NO2 pretreatment group. In
      summary, the pretreatment with OA-NO2 remarkably ameliorated the cisplatin
      induced kidney injury in mice, possibly via the inhibition of the inflammatory
      response, associated with the COX-2/mPGES-1/PGE2 cascade. 

PMID- 25861161
TI  - Effect of oral and vaginal hormonal contraceptives on inflammatory blood
      biomarkers.
AB  - The use of combined hormonal contraceptives has been reported to increase the
      level of C-reactive protein (CRP). We assessed the effect of hormonal
      contraceptive use on inflammatory cytokines including CRP, monocyte chemotactic
      protein-1, soluble tumor necrosis factor (sTNF), interleukin-6 (IL-6), and
      soluble CD40 ligand. We used 79 female subjects (19 to 30 years old) who were
      combined oral contraceptives users (n = 29), combined vaginal contraceptive users
      (n = 20), and nonusers (n = 30) with CRP values of <=1 (n = 46) or >=3 (n = 33).
      Information on medical history, physical activities, and dietary and sleeping
      habits were collected. Both oral and vaginal contraceptive users had higher
      levels of CRP (P < 0.0001), compared to nonusers. Only oral contraceptive users
      exhibited elevated sCD40L (P < 0.01). When comparing the groups with CRP <= 1 and
      CRP >= 3, levels of IL-6 and sTNF-RI were positively correlated with CRP among
      oral contraceptive users. We did not observe the same elevation for other
      inflammatory biomarkers for the CRP >= 3 group among vaginal contraceptive users.
      The clear cause of elevation in CRP level due to the use of different hormonal
      contraceptive formulations and methods is not well understood. Longitudinal
      studies with larger sample size are required to better assess the true cause of
      CRP elevation among hormonal contraceptive users. 

PMID- 25861162
TI  - Hypoxia and P. gingivalis synergistically induce HIF-1 and NF-kappaB activation
      in PDL cells and periodontal diseases.
AB  - Periodontitis is characterized by deep periodontal pockets favoring the
      proliferation of anaerobic bacteria like Porphyromonas gingivalis (P.
      gingivalis), a periodontal pathogen frequently observed in patients suffering
      from periodontal inflammation. Therefore, the aim of the present study was to
      investigate the signaling pathways activated by lipopolysaccharide (LPS) of P.
      gingivalis (LPS-PG) and hypoxia in periodontal ligament (PDL) cells. The relevant
      transcription factors nuclear factor-kappa B (NF-kappaB) and hypoxia inducible
      factor-1 (HIF-1) were determined. In addition, we analyzed the expression of
      interleukin- (IL-) 1beta, matrix metalloproteinase-1 (MMP-1), and vascular
      endothelial growth factor (VEGF) in PDL cells on mRNA and protein level. This was
      accomplished by immunohistochemistry of healthy and inflamed periodontal tissues.
      We detected time-dependent additive effects of LPS-PG and hypoxia on NF-kappaB
      and HIF-1alpha activation in PDL cells followed by an upregulation of IL-1beta,
      MMP-1, and VEGF expression. Immunohistochemistry performed on tissue samples of
      gingivitis and periodontitis displayed an increase of NF-kappaB, HIF-1, and VEGF
      immunoreactivity in accordance with disease progression validating the importance
      of the in vitro results. To conclude, the present study underlines the
      significance of NF-kappaB and HIF-1alpha and their target genes VEGF, IL-1beta,
      and MMP-1 in P. gingivalis and hypoxia induced periodontal inflammatory
      processes. 

PMID- 25861163
TI  - Macrophage migration inhibitory factor interacting with Th17 cells may be
      involved in the pathogenesis of autoimmune damage in Hashimoto's thyroiditis.
AB  - PURPOSE: To explore the possible role of MIF and Th17 cells in the thyroid
      specific autoimmune damage of Hashimoto's thyroiditis (HT). MATERIAL AND METHODS:
      We enrolled 40 HT patients and 30 healthy controls and divided HT patients into
      euthyroid subset (n = 22) and subclinical or overt hypothyroidism subset (n =
      18). The percentages of Th17 cells and expressions of MIF, interleukin 17A (IL
      17A) mRNA in PBMCs, as well as serum concentrations of MIF, and IL-17A, and
      thyroid functions, and thyroid-specific autoantibodies (TPOAb, TgAb) were
      detected by flow cytometry, real-time RT-PCR, ELISA, and ECLIA in all subjects.
      RESULTS: MIF mRNA, IL-17A mRNA expressions and Th17 cells percentages, serum MIF,
      and IL-17A protein levels were all significantly higher in HT patients, even in
      euthyroid subgroup. Additionally, the differences became more obvious in
      dysfunction subgroup. Importantly, both MIF levels and Th17 cells percentage were
      positively correlated with serum TPOAb, TgAb, and thyrotropin (TSH) levels in HT
      patients. CONCLUSIONS: These data suggest that MIF and Th17 cells increased
      dynamically and positively correlated with the markers of thyroid autoimmune
      damage, which indicated that interaction between MIF and Th17 cells may
      participate in the pathogenesis and development of thyroid-specific autoimmunity
      in HT.

PMID- 25861164
TI  - HT-29 and Caco-2 reporter cell lines for functional studies of nuclear factor
      kappa B activation.
AB  - The NF-kappaB is a transcription factor which plays a key role in regulating
      biological processes. In response to signals, NF-kappaB activation occurs via
      phosphorylation of its inhibitor, which dissociates from the NF-kappaB dimer
      allowing the translocation to the nucleus, inducing gene expression. NF-kappaB
      activation has direct screening applications for drug discovery for several
      therapeutic indications. Thus, pathway-specific reporter cell systems appear as
      useful tools to screen and unravel the mode of action of probiotics and natural
      and synthetic compounds. Here, we describe the generation, characterization, and
      validation of human epithelial reporter cell lines for functional studies of NF
      kappaB activation by different pro- and anti-inflammatory agents. Caco-2 and HT
      29 cells were transfected with a pNF-kappaB-hrGFP plasmid which contains the GFP
      gene under the control of NF-kappaB binding elements. Three proinflammatory
      cytokines (TNF-alpha, IL-1beta, and LPS) were able to activate the reporter
      systems in a dose-response manner, which corresponds to the activation of the NF
      kappaB signaling pathway. Finally, the reporter cell lines were validated using
      lactic acid bacteria and a natural compound. We have established robust Caco-2-NF
      kappaB-hrGFP and HT-29-NF-kappaB-hrGFP reporter cell lines which represent a
      valuable tool for primary screening and identification of bacterial strains and
      compounds with a potential therapeutic interest. 

PMID- 25861166
TI  - Revisiting the district level human resources for health architecture in
      Department of Public Health in Maharashtra.

PMID- 25861165
TI  - Sugar, salt, fat, and chronic disease epidemic in India: is there need for policy
      interventions?

PMID- 25861167
TI  - Models for primary eye care services in India.
AB  - Blindness and visual impairment continues to be a major public health problem in
      India. Availability and easy access to primary eye care services is essential for
      elimination of avoidable blindness. 'Vision 2020: The Right to Sight - India'
      envisaged the need for establishing primary eye care units named vision centers
      for every 50,000 population in the country by the year 2020. The government of
      India has given priority to develop vision centers at the level of community
      health centers and primary health centers under the 'National Program for Control
      of Blindness'. NGOs and the private sector have also initiated some models for
      primary eye care services. In the current situation, an integrated health care
      system with primary eye care promoted by government of India is apparently the
      best answer. This model is both cost effective and practical for the prevention
      and control of blindness among the underprivileged population. Other models
      functioning with the newer technology of tele-ophthalmology or mobile clinics
      also add to the positive outcome in providing primary eye care services. This
      review highlights the strengths and weaknesses of various models presently
      functioning in the country with the idea of providing useful inputs for eye care
      providers and enabling them to identify and adopt an appropriate model for
      primary eye care services. 

PMID- 25861168
TI  - Change management skills.

PMID- 25861169
TI  - Role of directorates in promoting nursing and midwifery across the various States
      of India: call for leadership for reforms.
AB  - BACKGROUND: While the roles and responsibilities of nursing professionals have
      multiplied over the years, but there are huge concerns with regard to the
      development of the nursing workforce and human resources (HR) issues for their
      career growth. The major lacuna is in not involving the nursing professionals in
      policy framing and decision-making. As a result, there is a leadership crisis of
      the nursing workforce across India. OBJECTIVES: The paper, is part of the WHO
      supported study, entitled "Study on Nursing and Midwifery in India: a critical
      review", is developed with the objective to review the current organizational and
      management structure for the nursing positions at the State Directorates in India
      and obtain a Leadership perspective to strengthen nursing management capacities
      to address maternal health issues. MATERIALS AND METHODS: The study descriptive
      and qualitative in nature and the sources of information were both primary and
      secondary collected from 16 states of India. RESULTS: Since none of the states
      have neither a Nursing Cell nor the post of Director Nursing, final decision
      making powers rest with state health secretaries and medical directors. The
      nursing management structure majorly managed by senior policy makers from the
      medical fraternity, and provides very little scope for nursing professionals to
      participate in policy decision making to bring about reforms. There is no
      uniformity on HR issues concerning career graphs and pay structures across the
      states. CONCLUSIONS: In order to strengthen nursing as a profession and for
      facilitating their role at the policy level, more powers and autonomy needs to be
      given to them and this requires HR policy guidelines for nurses. Setting up a
      separate nursing directorate, to be headed by a senior nursing professional, is
      suggested in every state along with a strong nursing division at the National
      level. This total paradigm shift will empower nursing professionals to take up
      the leadership role at the policy level to bring about necessary reforms. Across
      the country, nursing professionals repeatedly echoed one requirement: To reframe
      nursing leadership at all levels.

PMID- 25861170
TI  - Prevalence of Malnutrition and Relationship with Scholastic Performance among
      Primary and Secondary School Children in Two Select Private Schools in Bangalore
      Rural District (India).
AB  - BACKGROUND: Malnutrition is a serious problem among children in developing
      countries. In India; a school meal program is in place to combat malnutrition,
      but only in government schools. This study is an attempt to assess the prevalence
      of malnutrition in primary and secondary school children in private schools and
      to also assess the relationship between malnutrition and academic performance.
      MATERIALS AND METHODS: All 582 students from class 1-7 from two select schools in
      rural Bangalore, India were included in the study. Information on age of study
      subjects were collected from school records. Height and weight measurements were
      taken. BMI was calculated. Children were clinically examined for pallor. Data on
      height, weight and BMI was transformed into WHO 2007 Z scores and then was
      categorized as < -3 SD, -2 to -3 SD, > -2 SD, > 2 SD. Mathematics and English
      scores of the previous two class tests were taken, average scores were
      calculated. Statistical tests used were Chi square test, Odd's ratio, Chi square
      for trend. RESULTS: A total of 582 students participated in this study. Males
      were 54% (315) and females were 46% (267). One hundred and fifty-nine (27%) of
      the children had pallor, 81 (20%) had under nutrition, 38 (7%) had stunting, 197
      (34%) had thinness and 5 (1%) were found to be obese. Positive relationship was
      found between weight for ageZscores and English as well as Maths; Height for age
      Z scores with English. CONCLUSION: Hence we conclude that the prevalence of
      malnutrition is high among children in private schools also; and the nutritional
      status of the children is strongly associated with their academic performance.

PMID- 25861172
TI  - HIV-Risk Behavior Among the Male Migrant Factory Workers in a North Indian City.
AB  - BACKGROUND: Male migrants act as a bridge for transmitting infection from core
      risk groups to general population and hence this group becomes essential for the
      HIV control program. Migrant workers constitute a large proportion of workforce
      in India and HIV/AIDS epidemic in them would cause huge economic losses.
      OBJECTIVES: The aim of this study was to ascertain the HIV-risk behavior among
      male migrant factory workers. MATERIALS AND METHODS: This was a cross-sectional
      facility based survey conducted in 2011. Male migrant workers aged >=18 years,
      who were born outside Haryana, who had moved to current location after 15 years
      of age, who had worked in the current factory for at least one year, who were
      willing to participate and able to give valid consent were eligible. A
      consecutive sampling was done. Descriptive, bivariate and multiple logistic
      regression analyses were done. RESULTS: A total of 755 male subjects completed
      the interview. About 21.5% had experienced non-spousal sexual intercourse in last
      one year. Nearly 60% did not use a condom at the last non-spousal sex. Factors
      associated with recent non-spousal sex were being unmarried, younger age at
      migration, recent migration to Haryana, greater number of places migrated and
      lesser total duration of migration and those associated with non-use of condom at
      the last non-spousal sex were older age, lower education, lesser number of places
      migrated and lower level of HIV/AIDS knowledge. CONCLUSION: Unprotected, recent
      non-spousal sex was common among male migrants, which could increase their
      HIV/AIDS vulnerability.

PMID- 25861171
TI  - Prevalence and association of physical activity with obesity: an urban, community
      based, cross-sectional study.
AB  - AIM: To study levels of physical activity and various measures of obesity and
      their association in an urban population. STUDY DESIGN: Cross sectional.
      MATERIALS AND METHODS: One thousand and forty-seven individuals between the ages
      25-64 years systematically sampled from a community-based population database
      were contacted through a house-to-house survey. We adopted the WHO STEPS
      guidelines for conducting this study. Anthropological measures collected were
      height, weight, and waist and hip circumference. RESULTS: Physical Activity (PA)
      levels declined with age and the decline was greater among females. The Pearson's
      correlation coefficient for age against PA among males was found to be negative
      and weak (r = -0.104) and that among females was found to be similar (r = 
      0.206). The prevalence of obesity was higher among females (28.8 %) than among
      males (13.3 %) and the difference was statistically significant. There was a
      progressive increase in abdominal obesity with age in both genders. The
      prevalence of overweight and obesity was higher among individuals with low levels
      of PA as compared to those with high levels of PA. CONCLUSION: Sedentary behavior
      is prevalent in more than half of the current study sample. This was more so with
      increasing age, female gender and increasing obesity. PA is an important
      component on long-term weight control, and therefore adequate levels of activity
      should be prescribed to combat the obesity epidemic. Habitual moderate physical
      activity may be beneficial in preventing excess accumulation of fat.

PMID- 25861173
TI  - Barriers to improving patient safety in India: focus groups with providers in the
      southern state of kerala.
AB  - OBJECTIVE: To understand the perceptions of health care providers about barriers
      to improved patient safety in the Indian state of Kerala. MATERIALS AND METHODS:
      Five focus group discussions were held with 16 doctors and 20 nurses across three
      institutions (primary, secondary and tertiary care centers) in Kerala, India.
      Transcripts were analyzed by thematic analysis. SETTING: One rural primary care
      clinic, one secondary care hospital and one tertiary care center in Kerala,
      India. PARTICIPANTS: 16 doctors and 20 nurses participated in five focus groups.
      RESULTS: Overall, there were 129 unique mentions of barriers to patient safety;
      these barriers were categorized into five major themes. 'Limited resources' was
      the most prominent theme, followed by barriers related to health systems issues,
      the medical culture, provider training and patient education/awareness.
      CONCLUSIONS: Although inadequate resources are likely a substantial challenge to
      the improvement of patient safety in India, other patient safety barriers such as
      health systems changes, training, and education, could be addressed with fewer
      resources. While initial approaches to improving patient safety in India and
      other low- and middle-income countries have focused on implementing processes
      that represent best practices, this study suggests that multifaceted
      interventions to also address more structural problems (such as resource
      constraints, systems issues, and medical culture) may be important.

PMID- 25861174
TI  - Predictors of Sexually Transmitted Infections among Female Sex Workers (FSWs) in
      a City of Northern India.
AB  - INTRODUCTION: Sexually transmitted infections (STIs) and Reproductive tract
      infections RTIs are important public health problems in India. The prevalence of
      these infections is considerably higher among high risk groups (HRGs) ranging
      from 20-30%. It is high time that a study should be conducted to explore
      different factors and conditions responsible for the practice of unsafe sex among
      female sex workers (FSWs) in Uttar Pradesh (UP) and the impact of this on social
      life and health of FSWs. As Lucknow provides a comprehensive opportunity in terms
      of tourism, occupation, and economy, it becomes a potential hub for sex work.
      Studying FSW in Lucknow can thus be considered as a yardstick for the entire FSW
      population of UP population. The present study was thus planned with the
      objective of knowing the STI prevalence and its determinants among FSWs.
      MATERIALS AND METHODS: A cross-sectional descriptive study was conducted on FSWs
      registered with Targeted Intervention-Non-government Organization (TI-NGO),
      registered with Uttar Pradesh State Acquired Immuno Deficiency Syndrome (AIDS)
      Control Society (UPSACS) of Lucknow city. Total 288 subjects were studied.
      RESULTS: The average age of FSWs was 31 years. FSWs were mostly Hindus and
      illiterate. The overall prevalence of STI as per Syndromic diagnosis was found to
      be 35.8%. However, the percentage of FSWs with STI was higher in street-based
      (50.6%) than home-based (29.8%). Majority (42.7%) of sex workers with STI had non
      regular partners only while majority (52.4%) of sex workers without any STI had
      only regular partners. Condom usage with regular partners was poor. However, with
      the non-regular partners the condom usage was better. On multivariate analysis
      being single, having sex work as a sole means of earning, duration of sex work >
      2 years, having pallor, and giving in to client's demand for unsafe sex were
      found to be significant in causing STI. CONCLUSIONS: Prevalence of STI among the
      female sex workers as per Syndromic diagnosis was found to be 35.8%.
      Unemployment, anemia, and having sex without condom for extra money, failure to
      persuade the client and not doing anything were found to be important predictors
      for presence of STI.

PMID- 25861175
TI  - Making pregnancy safer-birth preparedness and complication readiness study among
      antenatal women attendees of a primary health center, delhi.
AB  - BACKGROUND: Every pregnancy is a joyful moment for all mothers who dream of a
      safe pregnancy and a healthy baby. However, every pregnant woman faces the risk
      of sudden, unpredictable complications that could end in death or injury to
      herself or to her infant. Birth preparedness and complication readiness (BPACR)
      is a strategy that encourages pregnant women, their families, and communities to
      effectively plan for births and deal with emergencies, if they occur. It is a key
      component of globally accepted safe motherhood programs. OBJECTIVES: The
      objective of our study was to assess the status of BPACR among pregnant women and
      to study the socio-demographic factors affecting BPACR. MATERIALS AND METHODS: We
      conducted a facility-based cross-sectional study among 417 antenatal attendees at
      a primary health center, Palam, New Delhi from January to April 2012. Knowledge
      about danger signs, planning for transport, place, and delivery by skilled birth
      attendant, financial management, and outcome were assessed. BPACR index was
      calculated. RESULTS: Our study revealed that the BPACR index was very low (41%)
      although the preparedness level was high. Majority (81.1%) had identified a
      skilled attendant at birth for delivery. Nearly half of the women (48.9%) had
      saved money for delivery and 44.1% women had also identified a mode of
      transportation for the delivery. However, only 179 (42.9%) women were aware about
      early registration of pregnancy. Only one-third (33.1%) of women knew about four
      or more antenatal visits during pregnancy. Overall, only 27.8% women knew about
      any one danger sign of pregnancy. CONCLUSION: The level of awareness regarding
      BPACR was very low (41%). Efforts should be targeted to increase the awareness
      regarding components of BPACR among pregnant women and their families at the
      Primary Health Center (PHC) as well as at the community level. This will indeed
      go a long way in reducing morbidity as well as mortality in pregnant women, thus
      enabling us to reach the millennium development goal.

PMID- 25861177
TI  - Curious case of accidental kerosene aspiration in an adolescent girl and blue
      colored carbonated soft drinks.

PMID- 25861178
TI  - Catch them young for healthy future.

PMID- 25861176
TI  - Dengue Fever outbreak in delhi, north India: a clinico-epidemiological study.
AB  - BACKGROUND: Dengue viruses, single-stranded positive polarity ribonucleic acid
      (RNA) viruses of the family Flaviviridae, are the most common cause of arboviral
      disease in the world. We report a clinico-epidemiological study of the dengue
      fever outbreak of 2010 from a tertiary care hospital in Delhi, North India.
      OBJECTIVES: Objectives of the study were to know the incidence of laboratory
      confirmed dengue cases among the clinically suspected patients; to study the
      clinical profile of dengue-positive cases; and to co-relate the above with the
      prevalent serotype and environmental conditions. MATERIALS AND METHODS: Four
      thousand three hundred and seventy serum samples from clinically suspected cases
      of dengue infection were subjected to MU-capture enzyme-linked immunosorbent
      assay (ELISA) for detection of dengue-virus-specific IgM antibodies. Virus
      isolation was done in 55 samples on C6/36 cell mono-layers. Clinical and
      demographic details of the patients were obtained from requisition forms of the
      patients or from treating clinicians. RESULTS: Out of the 4,370 serum samples,
      1,700 were positive for dengue-virus-specific IgM antibodies (38.9%). Prevalent
      serotype was dengue virus type-1. Thrombocytopenia and myalgia was seen in 23.1%
      and 18.3% of the 1,700 dengue IgM-positive patients, respectively. Also, 10.3% of
      1,700 were dengue hemorrhagic fever (DHF) patients; and the mortality in
      serologically confirmed dengue fever cases was 0.06%. CONCLUSIONS: A change in
      the predominant circulating serotype, unprecedented rains, enormous
      infrastructure development, and increased reporting due to improved diagnostic
      facilities were the factors responsible for the unexpected number of dengue fever
      cases confronted in 2010.

PMID- 25861179
TI  - Snoring: an annoyance or a serious health problem (obstructive sleep apnea)?

PMID- 25861180
TI  - Arterio venous malformation of the face: surgical treatment.
AB  - OBJECTIVE: This article reports a case of arteriovenous malformation of the face
      and upper lip. It discusses the diagnostic aids, surgical treatment and the
      results obtained. METHODS: A vascular malformation with Arterio venous shunts of
      the left cheek and upper lip was treated by surgical excision in a young 26 year
      old patient. Ligation of the feeding vessels followed by surgical excision has
      been discussed. The lesion was approached through modified Weber Fergusson
      incision with extension into contralateral lip. FOLLOW UP: Secondary cosmetic
      correction was done two months postoperatively. In a one year, there was no
      recurrence of the arteriovenous malformation with acceptable cosmetic results.
      CONCLUSIONS: A combined treatment including ligation of feeding vessels and
      surgical excision has been effective and safe in this patient. It was done due to
      cost factors, and inavailability of embolization facilities.The location and
      extent of a vascular malformation should dictate the preoperative investigations,
      surgical procedure and subsequent outcome.

PMID- 25861181
TI  - Trigemino-cardiac reflex during orbital floor reconstruction: a case report and
      review.
AB  - Trigemino-cardiac reflex is occurrence of hypotension and bradycardia upon
      surgical manipulation of areas supplied by the trigeminal nerve, and has been
      reported during craniofacial maxillofacial and ocular surgeries. Communication
      between the anaesthetic and surgical team is essential, and cessation of the
      precipitating stimulus is the first and most important therapeutic step. We
      report a case of immediate, reproducible, and reflexive response of Bradycardia
      and dysrhythmia upon manipulation of orbital fracture during orbital floor
      reconstruction in a 65-year-old man. Upon recognition of the reproducible
      relationship between falcine stimulation and increased vagal tone, the patient
      was given atropine in an effort to block cholinergic hyperactivity. After
      atropine administration, no further dysrhythmias occurred and surgery was carried
      uneventfully. 

PMID- 25861182
TI  - Multiple dentigerous cysts: a case report and review.
AB  - Dentigerous cysts are one of the common cysts of the jaws. Bilateral dentigerous
      cysts generally occur in association with a developmental syndrome or systemic
      diseases. Bilateral dentigerous cyst in absence of a syndrome is rare and to date
      only 18 cases have been reported. After reviewing the literature, no case reports
      of dentigerous cysts involving all the quadrants of the jaws were reported. As
      far as our knowledge, this is the first case to be reported. 

PMID- 25861183
TI  - Primary squamous cell carcinoma of the submandibular salivary gland: a rare
      entity.
AB  - Salivary gland tumors make up about 3% of all neoplasms of the head and neck.
      Salivary gland tumors vary widely in histopathological appearance, thus it
      prompted the development of a revised histopathological classification of
      tumours. Malignant tumors can arise in the major salivary glands or numerous
      minor salivary glands lining the mucosa of the upper aerodigestive tract. This
      case highlights one of the rare variants of primary squamous carcinoma of the sub
      mandibular salivary gland and the management of submandibular salivary gland
      malignancies. 

PMID- 25861184
TI  - Large cell neuroendocrine carcinoma: topic review and a unique case of metastasis
      to the mandible.
AB  - There are few reports of large cell neuroendocrine carcinoma (LCNEC) metastasis
      to the head and neck region, and no cases reporting LCNEC from lung metastasizing
      to the mandible. LCNEC is not well reported in the literature due to recent
      changes in the criteria for diagnosis, revised in 2004 by the world health
      organization, due to its propensity for rapid growth and low 5 year prognosis. We
      present a 61 year old female diagnosed with LCNEC of the lung in October, 2007
      treated with radiation and chemotherapy. Our patient had a PET scan performed in
      March, 2009 revealing no sign of metastasis. In July, 2009 she was seen for
      suspected sialadenitis by another department and referred to our oral and
      maxillofacial surgery clinic. Her signs and symptoms were consistent with
      metastatic disease to the mandible confirmed by histologic and
      immunohistochemical examination which revealed an invasive poorly differentiated
      non-small cell carcinoma. Palliative care was offered. Our patient died 2 years
      after initial diagnosis of lung cancer and 3 months after initial finding of
      metastatic disease. The rapid growth and spread of this cancer was surprising and
      knowledge of this cancer should be included in a differential diagnosis of
      expanding mandibular jaw lesions. 

PMID- 25861185
TI  - Long standing intra oral Acid burn.
AB  - Oral burn due to ingestion of corrosive substances can bring about debilitating
      consequences. It often brings mortality, and the survivors can have severe
      impairment of functions, especially in relation to the stomatognathic and
      gastrointestinal systems. This article presents a long-standing case (21 years)
      of an oral burn caused by a corrosive substance, its manifestation on growth and
      development of the face and its treatment. The patient was accidentally given
      acid orally when he was 4 months of age. He was treated at 21 years of age: the
      time he reported to us. This seems to be the first case report that describes the
      effects of long standing oral contracture secondary to burns on the growth and
      development of the maxillofacial structures and its treatment with a novel
      approach. 

PMID- 25861186
TI  - Osteolipoma of the oral cavity: a case report.
AB  - BACKGROUND: Osteolipoma located in the oral cavity and pharyngeal region is rare.
      CASE REPORT: The current case presents the clinical-ultrasonographic-radiographic
      histopathological features of the diagnosis and management of osteolipoma of the
      mandibular buccal mucosa. DISCUSSION: A literature review of the osteolipoma of
      the oral cavity and pharyngeal region is also presented. In this localization
      study, 14 well-documented cases could be found in English-language literature, in
      which the mean age of patients was 50.6 years, and slight predilection for male
      gender could be identified. The majority of cases appeared in the oral cavity (67
      %). The data demonstrated that osteolipoma of the oral cavity and pharyngeal
      region is an asymptomatic (80 %) lesion without bone attachment (80 %). The size
      of the lesions ranged from 8 to 90 mm in diameter (mean = 36 mm), with an
      evolution time ranging from 1 to 35 years (mean = 7.7 years). Similar to the
      present case, no recurrence could be identified in works which reported on the
      follow-up period.

PMID- 25861187
TI  - Solitary eosinophilic granuloma of mandibular condyle: literature review and
      report of a rare case.
AB  - Solitary eosinophilic granuloma (EG) is traditionally included as 1 of the 3
      clinical manifestations of the histiocytosis-X group of diseases, which also
      encompasses Hand-Schuller-Christian disease and Letterer-Siwe disease. EG is the
      most common lesion in the spectrum of disorders under the classification of
      Langerhans cell histiocytosis. EG represents the monostotic form of the disease
      with the head and neck region representing the most common site of initial
      presentation. We report a rare case of solitary EG involving mandibular condyle
      in a 49-year-old male patient, which is the first reported case in Indian
      literature. 

PMID- 25861188
TI  - Aggressive fibromatosis of the mandible in a two-month old infant.
AB  - Aggressive fibromatosis is a benign spindle cell tumor with locally infiltrative
      behavior and tendency to recur. It has overlapping features with other spindle
      cell lesions and hence it is pertinent to be distinguished from them as they have
      different treatment modalities. We report a rare case involving the mandible of a
      two-month old infant with histopathological, immunohistochemical and imaging
      features. 

PMID- 25861189
TI  - Self-regeneration of the mandible following hemimandibulectomy for ameloblastoma:
      a case report and review of literature.
AB  - Resection of the mandible with immediate or delayed graft reconstruction is
      widely used in the treatment of ameloblastoma involving a large portion of the
      mandible. The purpose of reconstruction is mainly to restore the esthetic
      appearance and mandibular function of the patient. Spontaneous regeneration of
      the mandible after resection is rarely encountered. This article reports a rare
      case of spontaneous regeneration of the mandible after hemimandibulectomy for
      ameloblastoma in a 16-year-old male patient. We discuss the theories pertaining
      to the mechanism and source of the new bone formation in this case and review the
      English literature. 

PMID- 25861190
TI  - Cherubism: a case report.
AB  - Cherubism is a benign, self-limiting fibro-osseous lesion characterized by
      bilateral symmetric painless expansion of jaw which is more prominent in mandible
      than in maxilla. Males are commonly affected (2:1) and with greater severity. It
      becomes noticeable in early childhood and gradually regresses after puberty.
      Although cherubism is considered as a familial/inherited disease but many
      sporadic cases have been reported in literature with no familial history.
      Osteoblastic and osteoclastic remodeling replaces normal bone by excessive amount
      of fibrovascular tissue containing multinucleated giant cells. Here, we present a
      case report of cherubism in a 10 year old boy describing the clinical,
      histological, biochemical and radiographic features. 

PMID- 25861191
TI  - Lymphocyte Depleted Hodgkin's Lymphoma Presented with Haemolytic Anemia: A Case
      Report and Literature Review.
AB  - Hodgkin's lymphoma accounts for ten per cent of all lymphomas. Lymphomas
      represent the third most frequent neoplasia on a worldwide scale and constitute 3
      % of malignant tumors. In the United States, there are about 8,000 new cases
      every year. This case report describes a case of lymphocyte-depletion Hodgkin's
      lymphoma (LDHL) manifested by anemia. LDHL is the least common of the types of
      Hodgkin's disease, comprising less than 1 % of all cases of this cancer. A 19
      year-old Indian male presented with complaint of huge asymptomatic swelling in
      the right lateral part of neck since 8 months. All the lymph nodes of the right
      side submandibular, submental, cervical and axillary lymph nodes were rubbery in
      consistency, tender and were palpable. The CBC revealed hemoglobin of 7.4 gm/dL
      and ESR count was highly raised up to 125 mm/first hour. Direct Coomb's test
      detected multiple antibodies IgG type, which was consistent with the diagnosis of
      Haemolytic anemia. Ultrasonography of the neck showed enlarged discrete lymph
      nodes on the right side of the neck. For further evaluation patient was subject
      for ultrasonography of the abdomen which revealed there was of enlargement of
      both spleen and liver. Lymph node FNAC revealed classic LDHL. Anemia and swelling
      resolved after completion of chemotherapy with adriamycin, bleomycin,
      vinblastine, and dacarbazine (ABVD) after 6 cycles. The literature review and our
      case report discuss the optimal management of this Hodgkin's lymphoma. To our
      knowledge, this is the first case of LDHL with Haemolytic Anemia treated with
      only ABVD regime. 

PMID- 25861192
TI  - Traumatic globe luxation associated with orbital fracture in a child: a case
      report and literature review.
AB  - Orbital fracture associated with traumatic globe luxation is rare, as it
      generally requires trauma with high energy for this to occur. The present case
      report focused on a child who had been hit by a motorcycle, leading to a globe
      luxation of the left eye and fractures of the superolateral orbital walls. The
      patient presented initial cosmetic and psychological benefits from the
      repositioning of the intact globe and the reduction of the orbital fractures.
      However, a subsequent evisceration of the globe was required due to persistent
      proptosis and pain. An ocular prosthesis was also implanted, thus recovering the
      patient's aesthetics. Thirty-four well-documented cases of traumatic globe
      luxation could be found in the English literature since 1970. The mean age of
      patients presenting traumatic globe luxation was 29.5 years. The male gender
      proved to be more prevalent, with traffic collisions representing the most common
      accident etiology. Direct orbital trauma with fractures of medial and floor walls
      displacing the globe into the maxillary sinus represented the most common injury
      mechanism (38.2 %), followed by an elongated object entering the orbit (26.5 %).
      Optical nerve avulsion is the most serious complication seen in association with
      traumatic globe luxation, with the repositioning of the initial globe, with no
      enucleation or evisceration, representing the main form of management. 

PMID- 25861193
TI  - Multifocal metastasizing extra-ocular facial sebaceous carcinoma as diagnostic
      challenge: case report and systematic review.
AB  - PURPOSE: Sebaceous carcinoma (SC) is a rare adnexal tumor. Extra-ocular, facial
      SC is very uncommon and local metastases are an extreme rare finding. A
      respective case is presented and discussed together with the current literature.
      CASE AND REVIEW: A tumor of the left ear of an 87-old male was primary excised
      together with multiple suspicious lesions of the head and neck. Most specimens
      were histopathologically rated as squamous cell carcinomas (SCC). Despite the in
      sano resection, additional new suspicious retro-auricular and temporal lesions
      were detected. Successive resections were diagnosed as basal cell carcinomas
      (BCC) and, because of a non-in-sano resection in a third approach, as SC. After
      reappraisal and immunhistochemical staining [epithelial membrane antigen (EMA),
      CK 5-6 and CD 15], most of the former specimens turned out to be SC as well. A
      literature search showed 3 reported cases of extra-ocular head and neck SC with
      cutaneous local metastases. In another review, in a total of 168 cases, SC was
      diagnosed after wrong initial histological diagnosis (SCC n = 56, BCC n = 44;
      other entity or precursors of carcinomas n = 68). CONCLUSION: Due to inconsistent
      histologic patterns, histopathological misdiagnosis of the uncommon facial SC and
      its metastases may complicate further therapy, prolong treatment and may lead to
      a worse prognosis of this neoplasm. A close interdisciplinary collaboration of
      clinician, surgeon and pathologist is of most relevance for the right diagnosis.

PMID- 25861194
TI  - Mandibular peripheral primitive neuroectodermal tumor: a rare case report with
      review of literature.
AB  - Primitive neuroectodermal tumor (PNET) is a high grade malignant neoplasm of
      small round cell tumor family, commonly affecting children and young adults.
      Peripheral primitive neuroectodermal tumor (pPNET) is a predominately neural,
      nonepithelial malignancy seen outside the nervous system that can arise in any
      place throughout the body including the diverse tissues of the head and neck. The
      diagnosis of PNET is confounded by its clinical and histopathological similarity
      to Ewing's sarcoma of the bone and has seldom been reported in the literature.
      The paucity of literature pertaining to the successful diagnosis and management
      of this lesion mandates its documentation and discussion. This article describes
      a case of an 11-year-old boy with an aggressive pPNET of the mandible. The
      clinical and radiographic presentations of this rare entity along with a detailed
      review on the current management modalities have been discussed. 

PMID- 25861195
TI  - Calcifying cystic odontogenic tumor in a 5-year-old boy: a case report.
AB  - The calcifying cystic odontogenic tumor (CCOT), formerly known as calcifying
      odontogenic cyst, is a rare developmental neoplasm/cyst of odontogenic epithelial
      origin with considerable histopathologic diversity and variable clinical
      behaviour. The occurrence of CCOT in the first decade of life is very uncommon.
      We report an interestingly rare variant of CCOT with ameloblastomatous
      proliferation affecting the mandibular left posterior region associated with an
      impacted permanent tooth in a 5-year-old boy. 

PMID- 25861196
TI  - A New Minimally Invasive Aesthetic Procedure for Correction of Frontal Coup de
      Sabre Deformity in Romberg's Syndrome.

PMID- 25861197
TI  - Plexiform unicystic ameloblastoma: a case report and data analysis in the Indian
      population.
AB  - Unicystic ameloblastoma (UA) among the different types of ameloblastomas is least
      encountered. The reason for lack of perception is paucity of case reports
      published in the literature. The UA, first described by Robinson and Martinez in
      1977, is relatively a rare type of ameloblastoma accounting for about 10-15 % of
      all ameloblastomas. The term, plexiform UA, refers to a pattern of one or more
      nodules of ameloblasts like cells projecting from the cystic lining into the
      lumen of the cyst. Here we present a case of swelling in the anterior mandible of
      a 25 year old male which on histological examination revealed plexiform UA, which
      was later treated by complete surgical excision. A tabular data analysis of the
      previous UAs occurring in the Indian population according to the cases reported
      by Pubmed has also been included. 

PMID- 25861198
TI  - A rare case report of mucinous cystadenoma with immunohistochemical analysis and
      review of literature.
AB  - Cystadenomas are rare salivary gland tumours characterised by prominent
      epithelium-lined papillary projections into the cystic spaces. A 37 year-old
      female, presented with a swelling on the right side of the hard palate.
      Clinically, the swelling was soft, fluctuant, sessile and non-tender measuring
      2.5 * 2 cm in diameter. Excisional biopsy was performed. The histopathological
      and immunohistochemical features were characteristic of mucinous cystadenoma.
      There has been no recurrence over a 2-year follow up period. The article
      highlights its clinical, histopathological, immunohistochemical features and
      differential diagnosis along with review of literature. Cystadenoma of the palate
      is rare, papillary variety being more common than mucinous with very few cases
      reported in literature. 

PMID- 25861199
TI  - Osseous plasma cell neoplasm of the mandible for initial diagnosis of multiple
      myeloma: case report and literature review.
AB  - PURPOSE: Plasmocytoma of the bone represents a variance of plasma cell neoplasms,
      which often gives hint for systemic affection. A case of a mandibular tumor as
      first manifestation of multiple myeloma (MM) is presented and discussed with the
      literature. MATERIALS AND METHODS: A 76-year old female with pain and swelling of
      the right lower jaw was assigned to the hospital. Radiograph showed a lytic tumor
      at the mandibular condyle and histological analysis gave evidence of a plasma
      cell tumor with positivity to CD138. In further examinations, elevated
      immunoglobulin levels in serum and osseous plasma cell infiltration unveiled MM.
      PubMed-database was searched by "multiple myeloma primary lesion jaw", "multiple
      myeloma primary manifestation mandible" and "multiple myeloma mandibular lesion"
      within the last 30 years. RESULTS: Together with the current case, 11 reports
      including 13 patients were found describing mandibular plasmocytoma as first sign
      for MM. Mean age was 59 years with slight female preference. Initial symptoms
      were mostly swelling episodes with or without pain. The main radiological
      presentation was a uni- or multilocular radiolucency. After a mean follow up time
      of 29 months (stated in 8 cases; standard deviation 50, min: 1, max: 151), 3/8
      patients died and in 5/8 cases, signs of progress were seen. CONCLUSION: In rare
      cases, occurrence of plasmocytoma of the mandible is first sign for MM and should
      always lead to further investigations regarding systemic disease. Simple
      examinations such as panoramic X-rays can lead to early detection of MM and
      thereby better prognosis by earlier treatment.

PMID- 25861200
TI  - Menopausal Hormone Therapy, can we safely use it in women with co-morbidities?

PMID- 25861201
TI  - Coronary atherosclerosis in noncardiac deaths: An autopsy study.
AB  - INTRODUCTION: Atherosclerosis leading to ischemic heart disease (IHD) is the most
      common cause of cardiac deaths worldwide. To evaluate the prevalence of
      atherosclerosis, an autopsy-based study conducted on subjects who died of
      noncardiac causes can be a valuable tool. With this hypothesis, we conducted this
      study on the hearts of subjects who died of noncardiac causes. MATERIALS AND
      METHODS: This study was conducted from August 2012 to February 2013 at Department
      of Pathology, BJ Medical College, Ahmedabad, Gujarat. The deceased patients who
      died of noncardiac causes and underwent autopsy at our hospital, their hearts
      were sent to our department for histopathological analysis. The hearts were fixed
      in 10% formalin, weighed, measured, and the three main coronary arteries were
      dissected out and carefully examined for any histological evidence of
      atherosclerotic plaques and associated pathological lesions and graded according
      to the classification given by American Heart Association. RESULTS: A total of
      250 autopsy cases were evaluated. Amongst them 113 were deaths due to noncardiac
      causes, of which 83 (73.45%) subjects had evidence of atherosclerosis. In the
      study, 68 (82%) were males and 15 (18%) were females. Left anterior descending
      artery (LADA; 69%) was the most commonly involved coronary artery. Triple vessel
      disease was found in 22% of subjects. CONCLUSION: The study showed alarmingly
      high prevalence of atherosclerosis. The pathogenesis of coronary atherosclerosis
      begins at a younger age in Indian population. Though the incidence of
      atherosclerosis is more common in males compared to females; coronary
      atherosclerosis is an important risk factor for IHDs in both sexes and screening
      for the same should begin at an early age.

PMID- 25861202
TI  - Safety and efficacy of gabapentin in management of psychosomatic and sexual
      symptoms in postmenopausal women: A pilot study.
AB  - OBJECTIVE: To evaluate safety and efficacy of gabapentin in management of
      psychosexual symptoms in postmenopausal women. MATERIALS AND METHODS: Fifty
      symptomatic postmenopausal females were randomly allocated into two groups; Group
      I received gabapentin 900 mg/day along with calcium 500 mg and Group II was given
      only calcium for 6 months and followed-up at 1,3, and 6 months. Data was analyzed
      in terms of percentage reduction of psychosomatic and sexual symptoms. Change in
      lipid profile and other blood parameters by the end of study were measured.
      RESULTS: Maximum improvement was seen in insomnia (90-98%) in gabapentin group.
      Improvement in anxiety was noted by 40.5, 49.5, and 53.8% at 1, 3, and 6 months,
      respectively, in Group I. While in Group II, maximum improvement noted was 18.6,
      19.7, and 20% at 1, 3, and 6 months, respectively. Similarly for depression,
      improvement was 40.4,47, and 49.5%at 1, 3, and 6 months, respectively, in Group
      I; while it was 15.4, 16.6, and 17% at 1, 3, and 6 months, respectively, in Group
      II. No significant improvement in vaginal dryness and dyspareunia noted at all
      follow-ups in either group. Somatic symptoms reduced by 33, 36.8, and 40% at 1,
      3, and 6 months, respectively, in Group I compared to 18% improvement at all
      follow-up in Group II. Low density lipoprotein (LDL) was raised in Group I
      significantly more than Group II. Other blood parameters were comparable in both
      groups. CONCLUSION: Gabapentin can lead to improvement in postmenopausal
      psychosomatic symptoms, while sexual symptoms show no improvement. Gabapentin can
      lead to increase in serum LDL, hence, precaution should be taken in patients with
      deranged lipid profile before starting therapy and it should be monitored during
      course of therapy. This drug can cause minor side effects like somnolence and
      dizziness.

PMID- 25861203
TI  - Menopausal symptoms and its effect on quality of life in urban versus rural
      women: A cross-sectional study.
AB  - AIM AND OBJECTIVE: To analyze the menopause-related symptoms and its impact on
      quality of life in post-menopausal women from urban and rural area. MATERIALS AND
      METHODS: A cross-sectional 1-year study was carried among women of urban (n =
      490) and rural (n = 380) areas, attending the outpatient department in the urban
      area and a house-to-house survey in rural areas, by interviews with the help of a
      pretested semi-structured standard questionnaire. For assessment of the
      menopausal symptoms menopause rating scale (MRS) and for quality of life, World
      Health Organization Quality of Life Scale (WHO QOL-BREF) questionnaire was used.
      RESULTS: There was a significant difference between the MRS total scores of the
      urban (14.67 +/- 6.64) and rural (16.08 +/- 7.65) group. The somatic,
      psychological, and urogenital symptoms were high in rural women than in urban
      women. The results were not significant for urogenital subscale. The mean raw
      scores of physical health, psychological, social relationships, and environmental
      domains was more in urban than in rural women. The mean transformed scores (4-20)
      of physical health, psychological, social relationships, and environmental
      domains was more in urban than in rural women. The mean transformed scores (0
      100) including the physical health, psychological, social relationships, and
      environmental domains was more in urban than in rural women. The result was not
      significant for physical health. CONCLUSION: The high proportions and the scores
      of MRS were observed in both rural and the urban women. The severity of symptoms
      was found more distressing for rural women. The quality of life in urban society
      was average and better than in rural women.

PMID- 25861204
TI  - Postmenopausal Women's Quality of Sleep and its Related Factors.
AB  - AIMS: To asses self-reported sleep disturbance and its associated factors in 50
      60-year-old Menopause women. SETTINGS AND DESIGN: This cross sectional study
      included 700 healthy 50-60-year-old women volunteers who were postmenopausal for
      at least 1 year. The volunteers were interviewed after providing informed
      consent. The study questioner included two main aspects: Personal characteristics
      and the Pittsburgh Sleep Quality Index (PSQI). Data were analyzed by using SPSS
      14 software. RESULTS: The mean sleep scale score was 7.84 +/- 4.4. Significant
      correlations had seen between sleep disturbance and characteristics of
      occupational status, educational status, husband's occupational status, and
      economical status, and (P = 0.002). There were no significant correlation between
      sleep disturbance and other personal characteristics, such as age; partner's age;
      number of children; family size; consumption of tea, coffee, or cola.
      CONCLUSIONS: Sleep disturbance is common in menopausal women. Taking into account
      the sleep-related personal characteristics, suitable interventions should be
      taken to improve sleep quality, which is a very important for maintaining the
      quality of life.

PMID- 25861205
TI  - Levonorgestrel intrauterine system (Mirena): An emerging tool for conservative
      treatment of abnormal uterine bleeding.
AB  - INTRODUCTION: To study the efficacy of levonorgestrel intrauterine system (LNG
      IUS; Mirena) in conservative management of abnormal uterine bleeding (AUB).
      MATERIALS AND METHODS: Seventy women between 30 and 55 years with AUB were
      included in a study conducted over a period of 3 years. Response was assessed
      monthly for first 4 months and then yearly for maximum 2 years. RESULTS: Mirena
      caused a 80% decrease in median menstrual blood loss (MBL) at 4 months, 95%
      decrease in MBL by 1 year, and 100% decrease (amenorrhea) by 2 years. Mean
      hemoglobin (Hb) % showed a significant rise of 7.8% from baseline 4 months post
      Mirena insertion. Mirena acted as an effective contraceptive in women not using
      any other form of contraception. Hysterectomy could be avoided in most of the
      women. CONCLUSION: Mirena provides an incredible nonsurgical alternative in
      treatment of menorrhagia. Its effects are reversible and it is an excellent
      fertility-sparing device. It is also an effective contraceptive.

PMID- 25861206
TI  - Cellular leiomyoma versus endometrial stromal tumor: A pathologists' dilemma.
AB  - Uterine smooth muscle tumors and endometrial stromal tumors (ESTs) are the two
      major types of mesenchymal tumors of the uterus, the latter being fairly
      uncommon. Among these, endometrial stromal sarcoma (ESS) accounts for 0.2-1.5% of
      all uterine malignancies. Although routine histopathological examination is
      sufficient to distinguish between ESS and smooth muscle tumors in most of the
      cases, the distinction between ESTs and highly cellular leiomyomas (CMs), on
      several occasions becomes a great diagnostic challenge for the pathologist. The
      differentiation between EST and CM is necessary on account of the variable
      clinical course and slight variation in the therapy. However, this is difficult
      due to the tendency of endometrial stromal cells to differentiate into well
      developed smooth muscle cells as well as overlapping immunohistochemical profile
      in some cases. We hereby report a series of cases which posed a diagnostic
      challenge to us as to whether they are CMs or ESTs. We therefore discuss the
      histological features which helped us resolve this dilemma as well as the utility
      of immunohistochemistry (IHC) as a diagnostic aid in arriving at a final
      diagnosis in such problematic cases. 

PMID- 25861207
TI  - Bilateral retiform variant of sertoli leydig cell tumour of ovary: An uncommon
      tumor with review of literature.
AB  - Sertoli-leydig cell tumors are the uncommon sex-cord stromal tumors of the ovary.
      We report a case of 42-year-old female with retiform variant of sertoli-leydig
      cell tumour. She presented with the complaint of mass in abdomen for 7 years.
      Ultrasound revealed bilateral ovarian mass suggestive of malignancy. Bilateral
      salpingo-oopherectomy with surgical staging was done. The tumor was diagnosed as
      stage I retiform variant of sertoli-leydig cell tumor on histopathology and
      immunohistochemistry. 

PMID- 25861208
TI  - Multilocular peritoneal inclusion cyst mimicking an ovarian tumor: A case report.
AB  - Peritoneal inclusion cysts are uncommon abdominopelvic cysts seen in
      perimenopausal women. It is often misdiagnosed clinically as an ovarian tumor due
      to similar presentation and mimicking findings on radiology. We describe a
      perimenopausal woman presenting with pelvic mass. Her clinical finding on
      radiology suggested an ovarian tumor; however, biopsy revealed it as peritoneal
      inclusion cysts. We discuss the possible ways to avoid such mistakes. 

PMID- 25861209
TI  - IVisTMSA: Interactive Visual Tools for Multiple Sequence Alignments.
AB  - IVisTMSA is a software package of seven graphical tools for multiple sequence
      alignments. MSApad is an editing and analysis tool. It can load 409% more data
      than Jalview, STRAP, CINEMA, and Base-by-Base. MSA comparator allows the user to
      visualize consistent and inconsistent regions of reference and test alignments of
      more than 21-MB size in less than 12 seconds. MSA comparator is 5,200% efficient
      and more than 40% efficient as compared to BALiBASE c program and FastSP,
      respectively. MSA reconstruction tool provides graphical user interfaces for four
      popular aligners and allows the user to load several sequence files at a time.
      FASTA generator converts seven formats of alignments of unlimited size into FASTA
      format in a few seconds. MSA ID calculator calculates identity matrix of more
      than 11,000 sequences with a sequence length of 2,696 base pairs in less than 100
      seconds. Tree and Distance Matrix calculation tools generate phylogenetic tree
      and distance matrix, respectively, using neighbor joining% identity and BLOSUM 62
      matrix. 

PMID- 25861210
TI  - A RESTful API for Access to Phylogenetic Tools via the CIPRES Science Gateway.
AB  - The CIPRES Science Gateway is a community web application that provides public
      access to a set of parallel tree inference and multiple sequence alignment codes
      run on large computational resources. These resources are made available at no
      charge to users by the NSF Extreme Science and Engineering Discovery Environment
      (XSEDE) project. Here we describe the CIPRES RESTful application programmer
      interface (CRA), a web service that provides programmatic access to all resources
      and services currently offered by the CIPRES Science Gateway. Software developers
      can use the CRA to extend their web or desktop applications to include the
      ability to run MrBayes, BEAST, RAxML, MAFFT, and other computationally intensive
      algorithms on XSEDE. The CRA also makes it possible for individuals with modest
      scripting skills to access the same tools from the command line using curl, or
      through any scripting language. This report describes the CRA and its use in
      three web applications (Influenza Research Database - www.fludb.org, Virus
      Pathogen Resource - www.viprbrc.org, and MorphoBank - www.morphobank.org). The
      CRA is freely accessible to registered users at
      https://cipresrest.sdsc.edu/cipresrest/v1; supporting documentation and
      registration tools are available at https://www.phylo.org/restusers. 

PMID- 25861211
TI  - Design and Implementation of a Comprehensive Web-based Survey for Ovarian Cancer
      Survivorship with an Analysis of Prediagnosis Symptoms via Text Mining.
AB  - Ovarian cancer (OvCa) is the most lethal gynecologic disease in the United
      States, with an overall 5-year survival rate of 44.5%, about half of the 89.2%
      for all breast cancer patients. To identify factors that possibly contribute to
      the long-term survivorship of women with OvCa, we conducted a comprehensive
      online Ovarian Cancer Survivorship Survey from 2009 to 2013. This paper presents
      the design and implementation of our survey, introduces its resulting data
      source, the OVA-CRADLETM (Clinical Research Analytics and Data Lifecycle
      Environment), and illustrates a sample application of the survey and data by an
      analysis of prediagnosis symptoms, using text mining and statistics. The OVA
      CRADLETM is an application of our patented Physio-MIMI technology, facilitating
      Web-based access, online query and exploration of data. The prediagnostic
      symptoms and association of early-stage OvCa diagnosis with endometriosis provide
      potentially important indicators for future studies in this field. 

PMID- 25861212
TI  - Network and pathway analysis of cancer susceptibility (a).

PMID- 25861213
TI  - HCsnip: An R Package for Semi-supervised Snipping of the Hierarchical Clustering
      Tree.
AB  - Hierarchical clustering (HC) is one of the most frequently used methods in
      computational biology in the analysis of high-dimensional genomics data. Given a
      data set, HC outputs a binary tree leaves of which are the data points and
      internal nodes represent clusters of various sizes. Normally, a fixed-height cut
      on the HC tree is chosen, and each contiguous branch of data points below that
      height is considered as a separate cluster. However, the fixed-height branch cut
      may not be ideal in situations where one expects a complicated tree structure
      with nested clusters. Furthermore, due to lack of utilization of related
      background information in selecting the cutoff, induced clusters are often
      difficult to interpret. This paper describes a novel procedure that aims to
      automatically extract meaningful clusters from the HC tree in a semi-supervised
      way. The procedure is implemented in the R package HCsnip available from
      Bioconductor. Rather than cutting the HC tree at a fixed-height, HCsnip probes
      the various way of snipping, possibly at variable heights, to tease out hidden
      clusters ensconced deep down in the tree. The cluster extraction process
      utilizes, along with the data set from which the HC tree is derived, commonly
      available background information. Consequently, the extracted clusters are highly
      reproducible and robust against various sources of variations that "haunted" high
      dimensional genomics data. Since the clustering process is guided by the
      background information, clusters are easy to interpret. Unlike existing packages,
      no constraint is placed on the data type on which clustering is desired.
      Particularly, the package accepts patient follow-up data for guiding the cluster
      extraction process. To our knowledge, HCsnip is the first package that is able to
      decomposes the HC tree into clusters with piecewise snipping under the guidance
      of patient time-to-event information. Our implementation of the semi-supervised
      HC tree snipping framework is generic, and can be combined with other algorithms
      that operate on detected clusters. 

PMID- 25861214
TI  - Case-based retrieval framework for gene expression data.
AB  - BACKGROUND: The process of retrieving similar cases in a case-based reasoning
      system is considered a big challenge for gene expression data sets. The huge
      number of gene expression values generated by microarray technology leads to
      complex data sets and similarity measures for high-dimensional data are
      problematic. Hence, gene expression similarity measurements require numerous
      machine-learning and data-mining techniques, such as feature selection and
      dimensionality reduction, to be incorporated into the retrieval process. METHODS:
      This article proposes a case-based retrieval framework that uses a k-nearest
      neighbor classifier with a weighted-feature-based similarity to retrieve
      previously treated patients based on their gene expression profiles. RESULTS: The
      herein-proposed methodology is validated on several data sets: a childhood
      leukemia data set collected from The Children's Hospital at Westmead, as well as
      the Colon cancer, the National Cancer Institute (NCI), and the Prostate cancer
      data sets. Results obtained by the proposed framework in retrieving patients of
      the data sets who are similar to new patients are as follows: 96% accuracy on the
      childhood leukemia data set, 95% on the NCI data set, 93% on the Colon cancer
      data set, and 98% on the Prostate cancer data set. CONCLUSION: The designed case
      based retrieval framework is an appropriate choice for retrieving previous
      patients who are similar to a new patient, on the basis of their gene expression
      data, for better diagnosis and treatment of childhood leukemia. Moreover, this
      framework can be applied to other gene expression data sets using some or all of
      its steps.

PMID- 25861215
TI  - Prognostic gene signature identification using causal structure learning:
      applications in kidney cancer.
AB  - Identification of molecular-based signatures is one of the critical steps toward
      finding therapeutic targets in cancer. In this paper, we propose methods to
      discover prognostic gene signatures under a causal structure learning framework
      across the whole genome. The causal structures are represented by directed
      acyclic graphs (DAGs), wherein we construct gene-specific network modules that
      constitute a gene and its corresponding regulators. The modules are then
      subsequently used to correlate with survival times, thus, allowing for a network
      oriented approach to gene selection to adjust for potential confounders, as
      opposed to univariate (gene-by-gene) approaches. Our methods are motivated by and
      applied to a clear cell renal cell carcinoma (ccRCC) study from The Cancer Genome
      Atlas (TCGA) where we find several prognostic genes associated with cancer
      progression - some of which are novel while others confirm existing findings. 

PMID- 25861216
TI  - Modeling discrete survival time using genomic feature data.
AB  - Researchers have recently shown that penalized models perform well when applied
      to high-throughput genomic data. Previous researchers introduced the generalized
      monotone incremental forward stagewise (GMIFS) method for fitting
      overparameterized logistic regression models. The GMIFS method was subsequently
      extended by others for fitting several different logit link ordinal response
      models to high-throughput genomic data. In this study, we further extended the
      GMIFS method for ordinal response modeling using a complementary log-log link,
      which allows one to model discrete survival data. We applied our extension to a
      publicly available microarray gene expression dataset (GSE53733) with a discrete
      survival outcome. The dataset included 70 primary glioblastoma samples from
      patients of the German Glioma Network with long-, intermediate-, and short-term
      overall survival. We tested the performance of our method by examining the
      prediction accuracy of the fitted model. The method has been implemented as an
      addition to the ordinalgmifs package in the R programming environment. 

PMID- 25861217
TI  - GeneMed: An Informatics Hub for the Coordination of Next-Generation Sequencing
      Studies that Support Precision Oncology Clinical Trials.
AB  - We have developed an informatics system, GeneMed, for the National Cancer
      Institute (NCI) molecular profiling-based assignment of cancer therapy (MPACT)
      clinical trial (NCT01827384) being conducted in the National Institutes of Health
      (NIH) Clinical Center. This trial is one of the first to use a randomized design
      to examine whether assigning treatment based on genomic tumor screening can
      improve the rate and duration of response in patients with advanced solid tumors.
      An analytically validated next-generation sequencing (NGS) assay is applied to
      DNA from patients' tumors to identify mutations in a panel of genes that are
      thought likely to affect the utility of targeted therapies available for use in
      the clinical trial. The patients are randomized to a treatment selected to target
      a somatic mutation in the tumor or with a control treatment. The GeneMed system
      streamlines the workflow of the clinical trial and serves as a communications hub
      among the sequencing lab, the treatment selection team, and clinical personnel.
      It automates the annotation of the genomic variants identified by sequencing,
      predicts the functional impact of mutations, identifies the actionable mutations,
      and facilitates quality control by the molecular characterization lab in the
      review of variants. The GeneMed system collects baseline information about the
      patients from the clinic team to determine eligibility for the panel of drugs
      available. The system performs randomized treatment assignments under the
      oversight of a supervising treatment selection team and generates a patient
      report containing detected genomic alterations. NCI is planning to expand the
      MPACT trial to multiple cancer centers soon. In summary, the GeneMed system has
      been proven to be an efficient and successful informatics hub for coordinating
      the reliable application of NGS to precision medicine studies. 

PMID- 25861218
TI  - Selective Mycobacterium tuberculosis Shikimate Kinase Inhibitors as Potential
      Antibacterials.
AB  - Owing to the persistence of tuberculosis (TB) as well as the emergence of
      multidrug-resistant and extensively drug-resistant (XDR) forms of the disease,
      the development of new antitubercular drugs is crucial. Developing inhibitors of
      shikimate kinase (SK) in the shikimate pathway will provide a selective target
      for antitubercular agents. Many studies have used in silico technology to
      identify compounds that are anticipated to interact with and inhibit SK. To a
      much more limited extent, SK inhibition has been evaluated by in vitro methods
      with purified enzyme. Currently, there are no data on in vivo activity of
      Mycobacterium tuberculosis shikimate kinase (MtSK) inhibitors available in the
      literature. In this review, we present a summary of the progress of SK inhibitor
      discovery and evaluation with particular attention toward development of new
      antitubercular agents. 

PMID- 25861219
TI  - Sex-Related Differences in Self-Reported Neurocognitive Impairment among High
      Risk Cocaine Users in Methadone Maintenance Treatment Program.
AB  - BACKGROUND: Previous research has suggested possible sex-related differences in
      executive functioning among cocaine users; however, no studies specifically
      explain sex-related differences in neurocognitive impairment (NCI) among cocaine
      users receiving clinical care. Knowledge about this association can aid in the
      development of targeted prevention strategies to reduce adverse health outcomes.
      This study was designed to examine the sex-related differences in NCI among high
      risk cocaine users receiving substance-abuse treatment. METHODS: The
      Neuropsychological Impairment Scale (NIS) was administered to 199 cocaine users
      (98 men; 101 women), receiving methadone maintainance treatment, to assess self
      reported NCI by identifying the patients' awareness of neuropsychological
      symptoms. We used T-test comparison to find differences in NCI between men and
      women and multiple regression analysis to explore the relative contribution of
      sex to NCI. RESULTS: Consistent with prior work, high NCI was evident within this
      sample, as indicated by high scores on most of the NIS subscales. Women reported
      greater impairment than men, as evidenced by significantly higher scores on
      several NIS subscales, after controlling for demographic and other confounding
      variables. Interestingly, cocaine craving significantly predicted NCI among men
      but not among women, as suggested by the significant association between cocaine
      craving and all except one of the NIS subscales. CONCLUSIONS: These findings
      suggest that cocaine users enter into treatment with a range of NCI - with women
      having significantly more neurocognitive deficits than men - that may contribute
      to differential treatment outcomes. This highlights the need to include
      additional services such as neuropsychological screening and sex-specific
      treatment programs to optimally reduce adverse health outcomes in these high
      risk, cognitively impaired patients.

PMID- 25861220
TI  - Evaluation of Pulmonary and Systemic Toxicity of Oil Dispersant (COREXIT
      EC9500A((r))) Following Acute Repeated Inhalation Exposure.
AB  - INTRODUCTION: Oil spill cleanup workers come into contact with numerous
      potentially hazardous chemicals derived from the oil spills, as well as chemicals
      applied for mitigation of the spill, including oil dispersants. In response to
      the Deepwater Horizon Macondo well oil spill in the Gulf of Mexico in 2010, a
      record volume of the oil dispersant, COREXIT EC9500A, was delivered via aerial
      applications, raising concern regarding potential health effects that may result
      from pulmonary exposure to the dispersant. METHODS: The current study examined
      the effects on pulmonary functions, cardiovascular functions, and systemic immune
      responses in rats to acute repeated inhalation exposure of COREXIT EC9500A at 25
      mg/m(3), five hours per day, over nine work days, or filtered air (control). At
      one and seven days following the last exposure, a battery of parameters was
      measured to evaluate lung function, injury, and inflammation; cardiovascular
      function; peripheral vascular responses; and systemic immune responses. RESULTS:
      No significant alterations in airway reactivity were observed at one or seven
      days after exposure either in baseline values or following methacholine (MCh)
      inhalation challenge. Although there was a trend for an increase in lung
      neutrophils and phagocyte oxidant production at one-day post exposure, there were
      no significant differences in parameters of lung inflammation. In addition,
      increased blood monocytes and neutrophils, and decreased lymphocyte numbers at
      one-day post exposure also did not differ significantly from air controls, and no
      alterations in splenocyte populations, or serum or spleen immunoglobulin M (IgM)
      to antigen were observed. There were no significant differences in peripheral
      vascular responsiveness to vasoconstrictor and vasodilator agonists or in blood
      pressure (BP) responses to these agents; however, the baseline heart rate (HR)
      and HR responses to isoproterenol (ISO) were significantly elevated at one-day
      post exposure, with resolution by day 7. CONCLUSIONS: In summary, acute repeated
      exposure to COREXIT EC9500A did not alter pulmonary function, lung
      injury/inflammation, systemic immune responses, or vascular tone, but did cause
      transient chronotropic effects on cardiac function.

PMID- 25861221
TI  - Occupational health and industrial hygiene.

PMID- 25861222
TI  - Free-radical Destruction of Sphingolipids Resulting in 2-hexadecenal Formation.
AB  - The action of hypochlorous acid (HOCl) and gamma-radiation on aqueous
      lysosphingolipid dispersions was found to produce 2-hexadecenal (Hex). This
      process includes the stages of formation of nitrogen-centered radicals from the
      starting molecules and the subsequent fragmentation of these radicals via the
      rupture of C-C and O-H bonds. These findings prove the existence of a
      nonenzymatic pathway of sphingolipid destruction leading to the formation of Hex,
      which possesses a wide spectrum of biological activity. Analysis of the effect of
      HOCl on transplantable rat glioma C6 cells and human embryonic kidney 293 cells
      points to the formation of Hex. This suggests that the described mechanism of
      free-radical destruction of sphingolipids may be replicated on cell culture under
      the stress of active chlorine forms. 

PMID- 25861223
TI  - Electrically induced limbic seizures: preliminary findings in a rodent model.
AB  - In epilepsy, novel pharmacological and nonpharmacological treatment approaches
      are commonly assessed in model systems of acute motor and often generalized
      seizures. We developed a rodent model with short-term electrical stimulation of
      the perforant path resulting in stereotyped limbic seizures. Limbic structures
      play a major role in human intractable epilepsy. In 10 rats, single electrical 5
      second and 20-Hz stimuli to the perforant path reliably produced limbic seizures
      characterized by resting behavior and subtle motor signs. Electrophysiological
      recordings from the dentate gyrus demonstrated a seizure pattern with 4-Hz to 5
      Hz discharges. Multiple inductions of seizures within 72 hours did not alter
      behavioral and electrophysiological seizure characteristics. Electrophysiological
      excitatory and inhibitory parameters assessed by evoked single and paired pulses
      did not change with increasing number of seizures. We present preliminary
      findings on a new model of electrically induced limbic seizures of mesiotemporal
      origin. This model may represent a reliable screening tool for new treatment
      approaches such as deep brain stimulation. 

PMID- 25861224
TI  - CD151-A Striking Marker for Cancer Therapy.
AB  - Cluster of differentiation 151 (CD151) is a member of the mammalian tetraspanin
      family, which is involved in diverse functions such as maintaining normal
      cellular integrity, cell-to-cell communication, wound healing, platelet
      aggregation, trafficking, cell motility and angiogenesis. CD151 also supports de
      novo carcinogenesis in human skin squamous cell carcinoma (SCC) and tumor
      metastasis. CD151 interacts with alpha3beta1 and alpha6beta4 integrins through
      palmitoylation where cysteine plays an important role in the association of CD151
      with integrins and non-integrin proteins. Invasion and metastasis of cancer cells
      were diminished by decreasing CD151 association with integrins. CD151 functions
      at various stages of cancer, including metastatic cascade and primary tumor
      growth, thus reinforcing the importance of CD151 as a target in oncology. The
      present review highlights the role of CD151 in tumor metastasis and its
      importance in cancer therapy. 

PMID- 25861225
TI  - The biologic syndrome of frailty in heart failure.
AB  - As we continue to care for an older and sicker end-stage heart failure
      population, it has become challenging to evaluate patients based on current risk
      scores that mainly focus on subjective symptoms and patient disability. For
      generations, geriatricians have sought to identify the body's underlying
      vulnerabilities that characterize frailty. More recently, cardiologists have
      begun to recognize this entity in their own practice. Several studies have
      suggested rates of frailty as high as 50% in patients with cardiovascular
      disease. However, despite recognizing frailty, it remains difficult to define.
      Like heart failure, frailty is a biologic syndrome that affects multiple organ
      systems. Measures of frailty are shown to strongly correlate with adverse
      outcomes in the health care system. 

PMID- 25861226
TI  - Atrial septal defects - clinical manifestations, echo assessment, and
      intervention.
AB  - Atrial septal defect (ASD) is a common congenital abnormality that occurs in the
      form of ostium secundum, ostium primum, sinus venosus, and rarely, coronary sinus
      defects. Pathophysiologic consequences of ASDs typically begin in adulthood, and
      include arrhythmia, paradoxical embolism, cerebral abscess, pulmonary
      hypertension, and right ventricular failure. Two-dimensional (2D) transthoracic
      echocardiography with Doppler is a central aspect of the evaluation. This
      noninvasive imaging modality often establishes the diagnosis and provides
      critical information guiding intervention. A comprehensive echocardiogram
      includes evaluation of anatomical ASD characteristics, flow direction, associated
      abnormalities (eg, anomalous pulmonary veins), right ventricular anatomy and
      function, pulmonary pressures, and the pulmonary/systemic flow ratio. The primary
      indication for ASD closure is right heart volume overload, whether symptoms are
      present or not. ASD closure may also be reasonable in other contexts, such as
      paradoxical embolism. ASD type and local clinical expertise guide choice of a
      percutaneous versus surgical approach to ASD closure. 

PMID- 25861227
TI  - Echocardiographic predictors of ventricular tachycardia.
AB  - BACKGROUND: Patients with structural heart disease are prone to ventricular
      tachycardia (VT) and ventricular fibrillation (VF), which account for the
      majority of sudden cardiac deaths (SCDs). We sought to examine echocardiographic
      parameters that can predict VT as documented by implantable cardioverter
      defibrillator (ICD) appropriate discharge. We examine echocardiographic
      parameters other than ejection fraction that may predict VT as recorded via rates
      of ICD discharge. METHODS: Analysis of 586 patients (469 males; mean age = 68 +/-
      3 years; mean follow-up time of 11 +/- 14 months) was undertaken. Echo parameters
      assessed included left ventricular (LV) internal end diastolic/systolic dimension
      (LVIDd, LVIDs), relative wall thickness (RWT), and left atrial (LA) size.
      RESULTS: The incidence of VT was 0.22 (114 VT episodes per 528 person-years of
      follow-up time). Median time-to-first VT was 3.8 years. VT was documented in 79
      patients (59 first VT incidence, 20 multiple). The echocardiographic parameter
      associated with first VT was LVIDs >4 cm (P = 0.02). CONCLUSION: The main
      echocardiographic predictor associated with the first occurrence of VT was LVIDs
      >4 cm. Patients with an LVIDs >4 cm were 2.5 times more likely to have an episode
      of VT. Changes in these echocardiographic parameters may warrant aggressive
      pharmacologic therapy and implantation of an ICD.

PMID- 25861228
TI  - A propensity score-matching analysis of transthoracic echocardiography and
      abdominal ultrasonography for the detection of abdominal aortic aneurysms.
AB  - INTRODUCTION: We previously reported that the prevalence of abdominal aortic
      aneurysms (AAAs) was higher in patients undergoing scheduled transthoracic
      echocardiography (TTE) than in patients undergoing abdominal ultrasonography
      (AUS); however, intergroup patient backgrounds differed significantly in that
      report. PURPOSE: We tested the hypothesis that TTE could detect AAA as
      effectively as AUS. DESIGN: A propensity score-matching analysis of a cross
      sectional study was adopted as the design for this study. METHODS: We enrolled
      7,619 and 15,433 patients scheduled to undergo TTE with additional evaluation of
      abdominal aorta at the end of the routine study and AUS, respectively, from 2009
      to 2010 in our hospital, as reported. A propensity score for profiles of patients
      who underwent TTE or AUS was developed to adjust for potential confounding bias.
      Consequently, 4,388 patients in each group were matched for analyses. RESULTS: In
      propensity-matched patients, AAA was detected in 59 patients of the TTE group and
      in 48 patients of the AUS group; the prevalence of AAA detection did not differ
      significantly between TTE and AUS groups (P = 0.331). Positive associations were
      observed between AAA detection and male sex (adjusted odds ratio [OR]: 3.25; 95%
      confidence interval [CI], 2.05-5.15; P < 0.001), older age (adjusted OR: 1.029;
      95% CI: 1.01-1.04; P < 0.001), and the presence of ischemic heart disease
      (adjusted OR: 1.78; 95% CI: 1.04-3.03; P = 0.033) and hypertension (adjusted OR:
      2.16; 95% CI: 1.38-3.37; P = 001). CONCLUSION: TTE detected AAA with comparable
      efficacy as AUS in propensity-matched groups who underwent scheduled TTE and AUS.

PMID- 25861229
TI  - "Reverse McConnell's Sign": Interpreting Interventricular Hemodynamic Dependency
      and Guiding the Management of Acute Heart Failure during Takotsubo
      Cardiomyopathy.
AB  - Although most patients with Takotsubo cardiomyopathy (TTC) have benign clinical
      course and prognosis, TTC can induce acute heart failure and hemodynamic
      instability. TTC mimics the clinical features of acute anterior wall myocardial
      infarction (AMI). Bedside clinicians often have a diagnostic dilemma when cardiac
      catheterization and angiography are either contraindicated or can cause potential
      adverse consequences. Misdiagnosing TTC as AMI will lead to initiation of harmful
      pharmacological or device-based treatment, which worsens hemodynamic compromise.
      Therefore, understanding and interpreting the unique pathophysiological and
      hemodynamic features of TTC in a better manner becomes crucial to guide effective
      clinical management of acute heart failure/cardiogenic shock during TTC. We
      review recent advances in echocardiographic diagnosis of TTC and its role in
      guiding bedside management of acute heart failure and cardiogenic shock, with
      specific focus on the interpretation of discrepant, but reciprocally dependent,
      left and right ventricular hemodynamics during acute stages of TTC. 

PMID- 25861230
TI  - A Case of IgG4-Related Hypophysitis Presented with Hypopituitarism and Diabetes
      Insipidus.
AB  - Immunoglobulin (Ig) G4-related systemic syndrome is a recently described entity
      characterized by elevated serum IgG4 and tissue infiltration of IgG4-positive
      plasma cells. Pituitary gland can be involved as hypophysitis. We report a case
      of a 72-year-old man, who presented with general fatigue and weakness. Laboratory
      tests revealed diabetes insipidus as well as hypopituitarism including adrenal
      insufficiency, hypogonadism, and hypothyroidism. His serum IgG4 was elevated. MR
      images showed enlargement of the pituitary stalk. Multiple nodules in bilateral
      kidneys were pointed out in the abdominal CT. Histological examination of the
      nodules showed increased IgG4-positive plasma cells. We diagnosed him with IgG4
      related kidney disease and hypophysitis. After treatment with hydrocortisone, his
      symptoms improved. The follow-up images showed that almost all renal nodules
      disap-peared and his pituitary stalk was shrinking. Our case appears to be very
      sensitive to glucocorticoid and suggests the possibility of treating IgG4-related
      hypophysitis successfully with a lower dose of glucocorticoid. 

PMID- 25861231
TI  - Shoulder pad sign and asymptomatic hypercalcemia in a patient with end-stage
      kidney disease.
AB  - Interpreting an abnormal serum calcium level in subjects with chronic kidney
      disease (CKD) requires the simultaneous evaluation of various clinical and
      laboratory parameters. An excessive intake of calcium salts and vitamin D
      overdosing may be the most common etiologies of hypercalcemia in individuals with
      advanced CKD. Nevertheless, it should be noted that such patients are susceptible
      to all diseases that may cause hypercalcemia in subjects without renal disease.
      In this report, we describe the case of a male chronic hemodialysis patient who
      developed asymptomatic hypercalcemia associated with polyarticular swelling. On
      the basis of the findings of systemic workup, he was finally diagnosed as having
      multiple myeloma. The so-called shoulder pad sign, which is pathognomonic for
      light chain amyloidosis, although its detection remains a challenge for
      physicians, was a clue leading to the prompt diagnosis of the disease in the
      current case. The impact of articular manifestations on the diagnostic strategy
      for assessing multiple myeloma is also discussed. 

PMID- 25861232
TI  - Klippel-trenaunay syndrome - a very rare and interesting syndrome.
AB  - Klippel-Trenaunay syndrome (KTS or KT) is an infrequently seen dermatological
      syndrome, which is often viewed as a triad of vascular malformation (capillary
      malformations or port-wine brands), venous varicosity, and soft tissue and/or
      bony hypertrophy. We report a case of a 12-year-old male who presented to us with
      the symptoms of varicose plaques over both lower limbs and was diagnosed as a
      case of KTS. Management is normally conservative and includes stockings for
      compression of the branches to reduce edema because of chronic venous
      insufficiency; modern devices that cause on and off pneumatic compression; and
      rarely, surgical correction of varicose veins with lifelong follow-up. The
      orthopedic abnormalities are treated with epiphysiodesis in order to prevent
      (stop) overgrowing of limb and correction of bone deformity. 

PMID- 25861233
TI  - Health economic evaluation of type 2 diabetes mellitus: a clinical practice
      focused review.
AB  - Type 2 diabetes mellitus (T2D) is a growing healthcare burden primarily due to
      long-term complications. Strict glycemic control helps in preventing
      complications, and early introduction of insulin may be more cost-effective than
      maintaining patients on multiple oral agents. This is an expert opinion review
      based on English peer-reviewed articles (2000-2012) to discuss the health
      economic consequences of T2D treatment intensification. T2D costs are driven by
      inpatient care for treatment of diabetes complications (40%-60% of total cost),
      with drug therapy for glycemic control representing 18% of the total cost.
      Insulin therapy provides the most improved glycemic control and reduction of
      complications, although hypoglycemia and weight gain may occur. Early treatment
      intensification with insulin analogs in patients with poor glycemic control
      appears to be cost-effective and improves clinical outcomes. 

PMID- 25861234
TI  - Immune checkpoint inhibitor therapy associated hypophysitis.
AB  - Ipilimumab is a monoclonal antibody directed against CTLA4 T-lymphocyte antigen
      used as cancer therapy. Immune-related adverse events are common side effects and
      may include hypophysitis-related hypopituitarism. The clinical features of six
      patients with ipilimumab-induced hypophysitis (IH) are described. The clinical
      features of IH reported in clinical trials, including the incidence of IH by
      gender and the likelihood of adrenal axis recovery, are summarized. Following the
      development of IH, most patients remain on glucocorticoid replacement despite
      efforts to withdraw therapy. Analysis of gender information in published clinical
      trials suggests that men are more prone to developing IH than women, and few
      patients fully recover the pituitary-adrenal axis function. Ipilimumab and other
      drugs within its class are likely to be used to treat many forms of cancer.
      Endocrinologists should anticipate a significant increase in the incidence of
      autoimmune hypophysitis. Strategies for early detection of IH and long-term
      management should be considered. 

PMID- 25861235
TI  - Effect of tamoxifen and raloxifene on the proliferative activity of the breast
      epithelium in premenopausal women.
AB  - OBJECTIVES: To compare the effects of tamoxifen and raloxifene on the
      proliferative activity of normal breast tissue in premenopausal women as measured
      by Ki-67/MIB-1 expression. STUDY DESIGN: A total of 48 women with benign breast
      nodules and a recommendation for surgical removal of the lesion took part in this
      study. They were randomized to use tamoxifen or raloxifene for 22 days, after
      which they were submitted to surgery. During the surgical procedure, a 1-cm
      fragment of normal breast tissue was removed to study Ki-67 expression. RESULTS:
      The mean percentage ratios between immunolabeled and non-labeled cells were 2.02
      +/- 1.09 and 3.13 +/- 3.23 for the tamoxifen and raloxifene groups, respectively.
      There was no statistically significant difference between the tamoxifen (n = 16)
      and raloxifene (n = 14) groups in relation to the immunohistochemical analysis of
      Ki-67 (P = 0.205). CONCLUSION: The results of this study showed no difference
      between tamoxifen and raloxifene with respect to the potential of these drugs to
      reduce the proliferative activity of the normal breast epithelium in
      premenopausal women.

PMID- 25861236
TI  - Ad-REIC Gene Therapy: Promising Results in a Patient with Metastatic CRPC
      Following Chemotherapy.
AB  - A 63-year-old man with metastatic castration-resistant prostate cancer (CRPC) was
      successfully treated for two years with in situ gene therapy using an adenovirus
      vector carrying the human REIC/Dkk-3 gene (Ad-REIC), following chemotherapy. Ad
      REIC mediates simultaneous induction of cancer-selective apoptosis and
      augmentation of antitumor immunity, and a Phase I/IIa clinical study on Ad-REIC
      has been conducted at Okayama University Hospital since January 2011. At the time
      of enrollment in December 2012, the patient presented with rapid progression of
      lymph node (LN) metastases. Two scheduled Ad-REIC injections and 10 additional Ad
      REIC injections into metastatic pelvic and para-aortic LNs under CT guidance,
      with an average four weeks' interval, exhibited the potent direct and indirect
      effects of Ad-REIC as a therapeutic cancer vaccine. During the next 12 months,
      three additional injections into para-aortic LNs showing regrowth achieved
      adequate control of all metastatic LNs with prostate-specific antigen (PSA)
      decline, without any particular adverse events. 

PMID- 25861237
TI  - Molecular cytogenetics in childhood acute lymphoblastic leukemia: a hospital
      based observational study.
AB  - OBJECTIVE: This study was conducted to determine the frequency of chromosomal
      aberrations in children aged <19 years with newly diagnosed acute lymphoblastic
      leukemia (ALL), attending/admitted in the Department of Pediatrics and
      Radiotherapy, Government Medical College, Jammu. Furthermore, we aimed to study
      the correlation between the cytogenetic molecular abnormalities and the immediate
      clinical outcome (induction of remission). MATERIALS AND METHODS: This was a
      prospective study conducted over a period of 2 years (May 2011 to May 2013) in a
      tertiary care hospital in India. Forty pediatric (1-19 years) patients (18 males,
      22 females; M: F = 0.8 : 1) with newly diagnosed ALL were studied for molecular
      cytogenetic analysis. Written consent was obtained from the parents of the
      patients. Bone marrow aspiration was done for making the diagnosis of ALL.
      Children lost to follow-up and who failed to give consent were excluded from the
      survey. Host factors and clinical parameters were obtained from patients.
      RESULTS: Bone marrow aspirate samples of 40 diagnosed cases of ALL were subjected
      to routine cytogenetic analysis, and reverse transcription-polymerase chain
      reaction (RT-PCR) technique was used for molecular analysis. Well-spread
      metaphase plates were obtained in 18/40 (45%) cases for analysis. RT-PCR revealed
      abnormal genes in 20/40 (50%) patients. The results of molecular cytogenetic
      analysis were correlated with patients' clinical and hematological parameters for
      risk stratification and immediate outcome (induction of remission). Eighteen out
      of 40 (45%) cases revealed no abnormality. Among the remaining 22 cases, 8 had
      TEL-AML1 (20%), 6 had BCR-ABL (15%), 4 had MLL-AF4 (10%), 2 had E2A-PBX1 (5%)
      fusion genes, and 2 had hyperdiploidy. To conclude, a higher proportion of cases
      in this study showed adverse translocations such as t (9;22), t (4;11), and t
      (1;19) compared to that reported in literature. CONCLUSION: RT-PCR assay was
      useful in detecting the prognostically significant oncogene fusion transcripts.
      In our study of 40 patients, we found that the pattern and frequency differ from
      those reported in Western literature. Our study reveals a lower frequency of
      hyperdiploidy (5%) and a higher frequency of BCR-ABL gene fusion (20%) in
      childhood ALL. Above all, in contrast to previous studies on childhood ALL, our
      study showed female predominance, with the male-to-female ratio being 0.8 : 1.
      Apart from the BCR-ABL fusion gene, none other was associated with poor
      prognosis. It is already well established that the characterization of the
      genetic entities at diagnosis is crucial for the understanding and the optimal
      treatment of ALL. Because the aberrations in our population differ significantly
      from those reported in Western populations, we may be required to tailor our
      protocols.

PMID- 25861238
TI  - Do premenopausal hypothyroid women on levothyroxine therapy need bone status
      monitoring?
AB  - BACKGROUND: Suppressive doses of levothyroxine therapy are reported to reduce
      bone mineral density (BMD) in women. Data on bone changes in premenopausal
      hypothyroid women with replacement therapy are limited. Hence, this study was
      undertaken to evaluate bone changes in this group using bone markers and BMD.
      MATERIALS AND METHODS: A hospital-based case-control study including 75
      premenopausal women aged 30-45 years was conducted. The subjects were categorized
      based on their thyroid function and history into three groups of 25 euthyroid, 25
      newly diagnosed hypothyroid, and 25 hypothyroid women on 100-200 MUg of
      levothyroxine for a minimum of 5 years. The bone changes were evaluated and
      compared among the groups biochemically by estimating their plasma osteocalcin
      and serum calcium and phosphorus and radiologically by measuring their BMD by
      quantitative ultrasonography. Statistical analysis was conducted by using
      analysis of variance, Tukey's test, and Pearson's correlation using IBM SPSS
      Statistics 20. RESULTS: Levels of plasma osteocalcin, serum calcium, and serum
      phosphorus in patients on long-term levothyroxine therapy were significantly
      higher than those in newly diagnosed hypothyroid women and in the euthyroid
      group. BMD showed definite features of osteopenia (T-score: -2.26 +/- 0.5) among
      the women in the treatment group, while it was well within the normal range in
      the newly diagnosed and euthyroid women. A significant correlation was found
      between the osteocalcin levels and T-score. CONCLUSION: Hypothyroid women on long
      term levothyroxine therapy showed signs of increased bone turnover and increased
      resorptive changes, though not frank osteoporosis. Hence, it may be important to
      evaluate the bone status of patients on levothyroxine for >5 years.

PMID- 25861239
TI  - Molecular Analysis of a Recurrent Sarcoma Identifies a Mutation in FAF1.
AB  - A patient presented with a recurrent sarcoma (diagnosed as leiomyosarcoma) 12
      years after the removal of an initial cancer (diagnosed as extracompartmental
      osteosarcoma) distally on the same limb. Following surgery, the sarcoma and
      unaffected muscle and bone were subjected to measurements of DNA exome sequence,
      RNA and protein expression, and transcription factor binding. The investigation
      provided corroboration of the diagnosis leiomyosarcoma, as the major
      upregulations in this tumor comprise muscle-specific gene products and calcium
      regulating molecules (calcium is an important second messenger in smooth muscle
      cells). A likely culprit for the disease is the point mutation S181G in FAF1,
      which may cause a loss of apoptotic function consecutive to transforming DNA
      damage. The RNA levels of genes for drug transport and metabolism were
      extensively skewed in the tumor tissue as compared to muscle and bone. The
      results suggest that the tumor represents a recurrence of a dormant metastasis
      from an originally misdiagnosed neoplasm. A loss of FAF1 function could cause
      constitutive WNT pathway activity (consistent with the downstream inductions of
      IGF2BP1 and E2F1 in this cancer). While the study has informed on drug transport
      and drug metabolism pharmacogenetics, it has fallen short of identifying a
      suitable target for molecular therapy. 

PMID- 25861240
TI  - The influence of APACHE II score on the average noise level in an intensive care
      unit: an observational study.
AB  - BACKGROUND: Noise levels in hospitals, especially in intensive care units (ICUs)
      are known to be high, potentially affecting not only the patients' well-being but
      also their clinical outcomes. In an observational study, we made a long-term
      measurement of noise levels in an ICU, and investigated the influence of various
      factors on the noise level, including the acute physiology and chronic health
      evaluation II (APACHE II) score. METHODS: The average noise level was
      continuously measured for three months in all (eight) patient rooms in an ICU,
      while the patient data were also registered, including the APACHE II score. The
      24-hour trend of the noise level was obtained for the patients of length-of-stay
      (LOS) >=1 day, which was compared to the timeline of the ICU routine events. For
      the patients with LOS >=4 days, the average noise levels in the first four days
      were analyzed, and regression models were established using the stepwise search
      method based on the Akaike information criterion. RESULTS: Features identified in
      the 24-hour trends (n = 55) agreed well with the daily routine events in the ICU,
      where regular check-ups raised the 10-minute average noise level by 2~3 dBA from
      the surrounding values at night, and the staff shift changes consistently
      increased the noise level by 3~5 dBA. When analyzed in alignment with the
      patient's admission (n=22), the daytime acoustic condition improved from Day 1 to
      2, but worsened from Day 2 to 4, most likely in relation to the various phases of
      patient's recovery. Regression analysis showed that the APACHE II score, room
      location, gender, day of week and the ICU admission type could explain more than
      50% of the variance in the daily average noise level, LAeq,24h. Where these
      factors were argued to have causal relations to LAeq,24h, the APACHE II score was
      found to be most strongly correlated: LAeq,24h increased by 1.3~1.5 dB when the
      APACHE II score increased by 10 points. CONCLUSIONS: Patient's initial health
      condition is one important factor that influences the acoustic environment in an
      ICU, which needs to be considered in observational and interventional studies
      where the noise in healthcare environments is the subject of investigation.

PMID- 25861241
TI  - Sonographic optic nerve sheath diameter as a surrogate measure for intracranial
      pressure in anesthetized patients in the Trendelenburg position.
AB  - BACKGROUND: It remains to be elucidated whether the Trendelenburg position
      increases intracranial pressure (ICP). ICP can be evaluated by measuring the
      sonographic optic nerve sheath diameter (ONSD). We investigated the effect of the
      isolated Trendelenburg position on ONSD in patients undergoing robot-assisted
      laparoscopic radical prostatectomy. Additionally, we evaluated the effect of the
      Trendelenburg position combined with pneumoperitoneum on ONSD. METHODS: Twenty
      one patients scheduled for robot-assisted laparoscopic radical prostatectomy were
      enrolled. Sonographic ONSDs and hemodynamic parameters were measured at specific
      time points: in the supine position after induction of anesthesia, 3 min after
      the steep Trendelenburg position (35 degrees  incline), 3 min after the steep
      Trendelenburg position combined with pneumoperitoneum, and in the supine position
      after desufflation of the pneumoperitoneum. RESULTS: The ONSD 3 min after the
      steep Trendelenburg position was significantly higher than that of the supine
      position after induction of anesthesia (5.1 +/- 0.3 mm vs. 4.5 +/- 0.4 mm). In
      addition, the ONSD 3 min after the steep Trendelenburg position combined with
      pneumoperitoneum was higher than that of the supine position after induction of
      anesthesia (4.9 +/- 0.4 mm vs. 4.5 +/- 0.4 mm). The ONSD in the supine position
      after desufflation of the pneumoperitoneum was similar to that in the supine
      position after induction of anesthesia. CONCLUSIONS: Use of the isolated steep
      Trendelenburg position, for even a short duration, increased the sonographic
      ONSD, providing a better understanding of the effect of only a transient steep
      Trendelenburg position on ONSD as a surrogate measure for ICP.

PMID- 25861242
TI  - Effect of differences in extubation timing on postoperative care following
      abdominal aortic replacement surgery: a comparison study.
AB  - BACKGROUND: Abdominal aortic replacement requires an extensive incision and
      strict blood pressure control, making rapid extubation of the tracheal tube and
      pain management difficult. The effects of extubation timing on the postoperative
      course and medical costs in the intensive care unit (ICU) were analyzed. METHODS:
      Patients who underwent elective abdominal aortic replacement were evaluated
      retrospectively. Patients were divided into those extubated on the day of surgery
      (Group A) and those extubated later (Group B). Group A was subdivided into
      extubation in the operating room (Group A1) or in the ICU (Group A2). Intubation
      time in the ICU, postoperative ICU stay, hospital stay, and total ICU expenses
      were compared among the four groups. RESULTS: Of the 191 patients, 95 were
      extubated on the day of surgery (Group A) and 96 later (Group B). The two groups
      differed in age and percutaneous coronary intervention history. Surgery and
      anesthesia durations, intraoperative infusion volume, and intraoperative bleeding
      amounts differed significantly in the two groups. Epidural anesthesia was given
      more frequently in Group A. Mean intubation time in the ICU (2.6 +/- 2.8 vs 17.4
      +/- 5.1 hours, P < 0.01), the ICU stay (2.1 +/- 0.3 vs 2.4 +/- 0.8 days, P <
      0.01), and the hospital stay (16.4 +/- 5.2 vs 20.2 +/- 12.5 days, P = 0.02) were
      significantly shorter, and total ICU expenses were significantly lower (1,036 +/-
      307 vs 1,565 +/- 1,072 dollars, P < 0.01), in Group A than in Group B. Of the 95
      patients in Group A, 34 were extubated in the operating room (Group A1) and 61 in
      the ICU (Group A2). Arrhythmia, epidural anesthesia, and the amount of
      intraoperative infusion amount were significantly higher, and the percentage of
      women significantly lower, in Group A1 (vs Group A2). Postoperative ICU and
      hospital stays and the ICU costs were not significantly different. CONCLUSION:
      Tracheal tube extubation on the day of abdominal aortic replacement surgery
      resulted in better postoperative course and lower costs than when extubation
      occurred later. Patients extubated in the operating room or the ICU on the day of
      surgery had similar postoperative courses and costs.

PMID- 25861243
TI  - Predictors of the accuracy of pulse-contour cardiac index and suggestion of a
      calibration-index: a prospective evaluation and validation study.
AB  - BACKGROUND: Cardiac Index (CI) is a key-parameter of hemodynamic monitoring.
      Indicator-dilution is considered as gold standard and can be obtained by
      pulmonary arterial catheter or transpulmonary thermodilution (TPTD; CItd).
      Furthermore, CI can be estimated by Pulse-Contour-Analysis (PCA) using arterial
      wave-form analysis (CIpc). Obviously, adjustment of CIpc to CItd initially
      improves the accuracy of CIpc. Despite uncertainty after which time accuracy of
      CIpc might be inappropriate, recalibration by TPTD is suggested after a maximum
      of 8 h. We hypothesized that accuracy of CIpc might not only depend on time to
      last TPTD, but also on changes of the arterial wave curve detectable by PCA
      itself. Therefore, we tried to prospectively characterize predictors of accuracy
      and precision of CIpc (primary outcome). In addition to "time to last TPTD" we
      evaluated potential predictors detectable solely by pulse-contour-analysis.
      Finally, the study aimed to develop a pulse-contour-derived "calibration-index"
      suggesting recalibration and to validate these results in an independent
      collective. METHODS: In 28 intensive-care-patients with PiCCO-monitoring (Pulsion
      Medical-Systems, Germany) 56 datasets were recorded. CIpc-values at baseline and
      after intervals of 1 h, 2 h, 4 h, 6 h and 8 h were compared to CItd derived from
      immediately subsequent TPTD. Results from this evaluation-collective were
      validated in an independent validation-collective (49 patients, 67 datasets).
      RESULTS: Mean bias values CItd-CIpc after different intervals ranged between 
      0.248 and 0.112 L/min/m(2). Percentage-error after different intervals to last
      TPTD ranged between 18.6% (evaluation, 2 h-interval) and 40.3% (validation, 6 h
      interval). In the merged data, percentage-error was below 30% after 1 h, 2 h, 4 h
      and 8 h, and exceeded 30% only after 6 h. "Time to last calibration" was neither
      associated to accuracy nor to precision of CIpc in any uni- or multivariate
      analysis. By contrast, the height of CIpc and particularly changes in CIpc
      compared to last thermodilution-derived CItd(base) univariately and independently
      predicted the bias CItd-CIpc in both collectives. Relative changes of CIpc
      compared to CItd(base) exceeding thresholds derived from the evaluation
      collective (-11.6% < CIpc-CItd(base)/CItd(base) < 7.4%) were confirmed as
      significant predictors of a bias |CItd-CIpc| >= 20% in the validation-collective.
      CONCLUSION: Recalibration triggered by changes of CIpc compared to CItd(base)
      derived from last calibration should be preferred to fixed intervals.

PMID- 25861244
TI  - Interferon gamma polymorphisms and hepatitis B virus-related liver cirrhosis risk
      in a Chinese population.
AB  - BACKGROUND: Previous studies proved that interferon gamma (IFN-gamma) gene
      polymorphisms were associated with the risk of hepatitis B virus (HBV) infection.
      However, the association between IFN-gamma polymorphisms and HBV-related liver
      cirrhosis (HBV-LC) risk is still unclear. METHODS: IFN-gamma +874 T/A and
      +2109G/A genotypes were determined in 126 HBV-LC patients, 129 chronic hepatitis
      B(CHB) patients, and 173 early HBV infection controls using a sequence-specific
      primer-polymerase chain reaction and a polymerase chain reaction-restriction
      fragment length polymorphism, respectively. RESULTS: Significant associations
      were observed between +2109A/G polymorphisms and HBV-LC risk in the co-dominant
      model (GG vs. AA: OR = 0.321, 95% CI = 0.130-0.793, P = 0.014), the allelic model
      (OR = 0.565, 95% CI = 0.388-0.825, P = 0.003), the dominant model (OR = 0.551,
      95% CI = 0.344-0.883, P = 0.013), and the recessive model (OR = 0.385, 95% CI =
      0.159-0.930, P = 0.034). In addition, haplotype analysis indicated that the
      T(+874)G(+2109) haplotype significantly decreased the HBV-LC risk (OR = 0.106,
      95% CI = 0.022-0.502, P = 0.000), and A(+874)A(+2109) haplotype significantly
      increased the LC risk (OR = 1.485, 95% CI = 1.065-2.070, P = 0.019). No
      significant associations were observed between IFN-gamma +874 T/A polymorphisms
      and HBV-LC risk, as well as the two single-nucleotide polymorphisms (SNPs) and
      CHB risk (P > 0.05). CONCLUSIONS: Our observations suggested a significant
      association of IFN-gamma polymorphisms with HBV-LC risk in the Chinese
      population.

PMID- 25861245
TI  - TNF-alpha and IL-6 inhibit apolipoprotein A-IV production induced by linoleic
      acid in human intestinal Caco2 cells.
AB  - BACKGROUND: Apolipoprotein A-IV (apoA-IV) is a protein mainly synthesized by
      enterocytes in the intestine. Its gene expression is suppressed during fasting
      and stimulated during active fat absorption. Chronic feeding of a high-fat (HF)
      diet abolishes the differential expression between fasting and fat-feeding and
      therefore may contribute to diet-induced obesity since apoA-IV is a potent
      satiety factor. It is well established that the circulating pro-inflammatory
      cytokines TNF-alpha and IL-6 are increased by HF feeding. METHODS: To determine
      whether pro-inflammatory cytokines are involved in the diminished response of
      apoA-IV gene expression to fat-feeding, different concentrations of linoleic acid
      (LA), an important dietary fatty acid, was used to stimulate apoA-IV expression
      in human intestinal Caco2 cells. Cells were pre-treated with or without human
      recombinant TNF-alpha, IL-6 or their combination before the addition of LA. Real
      time PCR and ELISA were used to detect and quantify RNA transcripts and proteins
      of apoA-IV and the cytokines. RESULTS: LA stimulated gene and protein expression
      of apoA-IV in a dose and time dependent manner. Pre-treatment with the cytokines
      for 72 h significantly inhibited the increased expression of apoA-IV gene and
      protein induced by LA. Furthermore, the cytokines, especially TNF-alpha, also
      positively up-regulate the cytokine themselves in Caco2 cells. CONCLUSIONS: Our
      data indicate that the pro-inflammatory cytokines may be responsible for the
      reduced apoA-IV production in response to fat feeding. Because of apoA-IV's role
      in satiety, we propose the inhibitory effect of circulating pro-inflammatory
      cytokines on apoA-IV production contributes to diet-induced obesity.

PMID- 25861246
TI  - The protective effects of chronic intermittent hypobaric hypoxia pretreatment
      against collagen-induced arthritis in rats.
AB  - OBJECTIVE: To explore the immunological mechanisms underlying the effect of
      chronic intermittent hypobaric hypoxia (CIHH) pretreatment on collagen-induced
      arthritis (CIA) in rat. METHODS: Fifty-four adult male Sprague-Dawley rats were
      used in the experiment. Arthritis in CIA rats (n=18) was induced by injection of
      collagen. The CIHH+CIA rats (n=18) were treated with CIHH (simulated 3000 m
      altitude, 5 hours per day for 28 days, PO2=108.8 mmHg) before CIA. The control
      rats (n=18) were not given any treatment. RESULTS: (1) Incidence rate of CIA in
      CIHH+CIA rats was significantly lower than that in CIA rats (P<0.05). (2) The paw
      thickness and arthritis index (AI) value in CIHH+CIA rats were lower than those
      in CIA rats (P<0.05). (3) The hyperplasia with inflammatory infiltration in
      synovial tissue of joints in CIHH+CIA rats was much alleviative compared with CIA
      rats. (4) TNF-alpha, IFN-gamma, IL-4 and IL-17 in synovial tissue of joint and
      serum in CIHH+CIA rats were decreased compared with CIA rats (P<0.05). (5) The
      number of CD4-positive T-lymphocytes and the ratio of CD4/CD8 T-lymphocytes in
      peripheral blood in CIHH+CIA rats were lower than those in CIA rats (P<0.05). (6)
      The protein expression of HIF-1alpha and NF-kappaB in synovial tissue of joint in
      CIHH+CIA rats was decreased compared with CIA rats (P<0.05). CONCLUSION: CIHH
      pretreatment has a protective effect against collagen-induced arthritis in rat
      through down-regulation of HIF-1alpha and NF-kappaB, inhibition of inflammatory
      cytokines TNF-alpha and IL-17, and balance in CD4/CD8 and Th1/Th2 T lymphocytes.

PMID- 25861247
TI  - Chronic Kidney Disease is associated with an increase of Intimal Dendritic cells
      in a comparative autopsy study.
AB  - BACKGROUND: Chronic Kidney Disease (CKD) and inflammation are risk factors for
      atherosclerotic vascular disease (ASVD). In inflammatory conditions, Nuclear
      Factor-kappaB (NF-kappaB) is frequently activated and it has been detected in
      human ASVD. In this work, we investigated if the degree of inflammation and of NF
      kappaB activation were increased in the aorta of patients with CKD. METHODS: This
      is a case-control pilot study performed on 30 abdominal aorta samples from 10
      human autopsies. Cases were patients with CKD and controls patients with normal
      glomerular filtration rate (eGFR). Infiltrating mononuclear cells (S100(+),
      CD3(+), CD40(+), CD40L(+)) and activation of NF-kappaB were identified by
      immunohistochemistry. FINDINGS: The number of cells in the intima which showed
      activated nuclear NF-kappaB correlated with severity of ASVD lesions (r = 0.56, p
      = 0.003), with numbers of CD3(+) lymphocytes in adventitia (r = 0.50, p = 0.008),
      with numbers of CD40(+) cells in the intima (r = 0.59, p = 0.002) or in the
      adventitia (r = 0.45, p = 0.02), and with numbers of CD40L(+) cells in the intima
      (r = 0.51, p = 0.011). Increased numbers of S100+ Intimal Dendritic cells (IDCs)
      were associated with ASVD (p = 0.03) and CKD (p = 0.01). CONCLUSIONS: Number of
      CD3(+) cells, of CD40(+) cells, of CD40L(+) cells and the degree of NF-kappaB
      activation were increased in ASVD lesions suggesting a role for the adaptive T
      cell in the development of ASVD lesions. IDCs were associated both with ASVD and
      CKD suggesting a role of these cells in the pathogenesis of ASVD in CKD.

PMID- 25861248
TI  - The determinants of technical efficiency of a large scale HIV prevention project:
      application of the DEA double bootstrap using panel data from the Indian Avahan.
AB  - BACKGROUND: In 2004, the largest HIV prevention project (Avahan) conducted
      globally was implemented in India. Avahan was implemented by NGOs supported by
      state lead partners in order to provide HIV prevention services to high-risk
      population groups. In 2007, most of the NGOs reached full coverage. METHODS:
      Using a panel data set of the NGOs that implemented Avahan, we investigate the
      level of technical efficiency as well as the drivers of technical inefficiency by
      using the double bootstrap procedure developed by Simar & Wilson (2007). Unlike
      the two-stage traditional method, this method allows valid inference in the
      presence of measurement error and serial correlation. RESULTS: We find that over
      the 4 years, Avahan NGOs could have reduced the level of inputs by 43% given the
      level of outputs reached. We find that efficiency of the project has increased
      over time. Results indicate that main drivers of inefficiency come from the
      characteristics of the state lead partner, the NGOs and the catchment area.
      CONCLUSION: These organisational factors are important to explicitly consider and
      assess when designing and implementing HIV prevention programmes and in setting
      benchmarks in order to optimise the use and allocation of resources. JEL
      CLASSIFICATIONS: C14, I1.

PMID- 25861249
TI  - Optic disc segmentation by balloon snake with texture from color fundus image.
AB  - A well-established method for diagnosis of glaucoma is the examination of the
      optic nerve head based on fundus image as glaucomatous patients tend to have
      larger cup-to-disc ratios. The difficulty of optic segmentation is due to the
      fuzzy boundaries and peripapillary atrophy (PPA). In this paper a novel method
      for optic nerve head segmentation is proposed. It uses template matching to find
      the region of interest (ROI). The method of vessel erasing in the ROI is based on
      PDE inpainting which will make the boundary smoother. A novel optic disc
      segmentation approach using image texture is explored in this paper. A cluster
      method based on image texture is employed before the optic disc segmentation step
      to remove the edge noise such as cup boundary and vessels. We replace image force
      in the snake with image texture and the initial contour of the balloon snake is
      inside the optic disc to avoid the PPA. The experimental results show the
      superior performance of the proposed method when compared to some traditional
      segmentation approaches. An average segmentation dice coefficient of 94% has been
      obtained. 

PMID- 25861250
TI  - Nitrooleic Acid Attenuates Lipid Metabolic Disorders and Liver Steatosis in DOCA
      Salt Hypertensive Mice.
AB  - Nitrooleic acid (OA-NO2) is endogenous ligands for peroxisome proliferator
      activated receptors. The present study was aimed at investigating the beneficial
      effects of OA-NO2 on the lipid metabolism and liver steatosis in
      deoxycorticosterone acetate- (DOCA-) salt induced hypertensive mice model. Male
      C57BL/6 mice were divided to receive DOCA-salt plus OA-NO2 or DOCA-salt plus
      vehicle and another group received neither DOCA-salt nor OA-NO2 (control group).
      After 3-week treatment with DOCA-salt plus 1% sodium chloride in drinking fluid,
      the hypertension was noted; however, OA-NO2 had no effect on the hypertension. In
      DOCA-salt treated mice, the plasma triglyceride and total cholesterol levels were
      significantly increased compared to control mice, and pretreatment with OA-NO2
      significantly reduced these parameters. Further, the histopathology of liver
      exhibited more lipid distribution together with more serious micro- and
      macrovesicular steatosis after DOCA-salt treatment and that was consistent with
      liver tissue triglyceride and nonesterified fatty acids (NEFA) content. The mice
      pretreated with OA-NO2 showed reduced liver damage accompanied with low liver
      lipid content. Moreover, the liver TBARS, together with the expressions of
      gp91phox and p47phox, were parallelly decreased. These findings indicated that OA
      NO2 had the protective effect on liver injury against DOCA-salt administration
      and the beneficial effect could be attributed to its antihyperlipidemic
      activities. 

PMID- 25861251
TI  - Huaier Cream Protects against Adriamycin-Induced Nephropathy by Restoring
      Mitochondrial Function via PGC-1alpha Upregulation.
AB  - The mechanism by which Huaier, a Chinese traditional medicine, protects podocytes
      remains unclear. We designed the present study to examine whether mitochondrial
      function restored by PGC-1alpha serves as the major target of Huaier cream in
      protecting ADR nephropathy. After ADR administration, the podocytes exhibited
      remarkable cell injury and mitochondrial dysfunction. Additionally, ADR also
      reduced PGC-1alpha both in vivo and in vitro. Following the Huaier treatment, the
      notable downregulation of PGC-1alpha and its downstream molecule mitochondrial
      transcription factor A (TFAM) were almost entirely blocked. Correspondingly,
      Huaier markedly ameliorated ADR-induced podocyte injury and mitochondrial
      dysfunction in both rat kidneys and incubated cells as it inhibited the decrease
      of nephrin and podocin expression, mtDNA copy number, MMP, and ATP content.
      Transmission electron microscopy result also showed that Huaier protected
      mitochondria against ADR-induced severe mitophagy and abnormal changes of
      ultrastructural morphology. In conclusion, Huaier can protect podocytes against
      ADR-induced cytotoxicity possibly by reversing the dysfunction of mitochondria
      via PGC-1alpha overexpression, which may be a novel therapeutic drug target in
      glomerular diseases. 

PMID- 25861252
TI  - A fast clustering algorithm for data with a few labeled instances.
AB  - The diameter of a cluster is the maximum intracluster distance between pairs of
      instances within the same cluster, and the split of a cluster is the minimum
      distance between instances within the cluster and instances outside the cluster.
      Given a few labeled instances, this paper includes two aspects. First, we present
      a simple and fast clustering algorithm with the following property: if the ratio
      of the minimum split to the maximum diameter (RSD) of the optimal solution is
      greater than one, the algorithm returns optimal solutions for three clustering
      criteria. Second, we study the metric learning problem: learn a distance metric
      to make the RSD as large as possible. Compared with existing metric learning
      algorithms, one of our metric learning algorithms is computationally efficient:
      it is a linear programming model rather than a semidefinite programming model
      used by most of existing algorithms. We demonstrate empirically that the
      supervision and the learned metric can improve the clustering quality. 

PMID- 25861253
TI  - A pressure control method for emulsion pump station based on Elman neural
      network.
AB  - In order to realize pressure control of emulsion pump station which is key
      equipment of coal mine in the safety production, the control requirements were
      analyzed and a pressure control method based on Elman neural network was
      proposed. The key techniques such as system framework, pressure prediction model,
      pressure control model, and the flowchart of proposed approach were presented.
      Finally, a simulation example was carried out and comparison results indicated
      that the proposed approach was feasible and efficient and outperformed others. 

PMID- 25861254
TI  - Management of pruritus in chronic liver disease.
AB  - Background. There continues to be uncertainty on the ideal treatment of pruritus
      in chronic liver disease. The aim of this study was to gather the latest
      information on the evidence-based management of pruritus in chronic liver
      disease. Methodology. A literature search for pruritus in chronic liver disease
      was conducted using Pubmed and Embase database systems using the MeSH terms
      "pruritus," "chronic liver disease," "cholestatic liver disease," and
      "treatment." Results. The current understanding of the pathophysiology of
      pruritus is described in addition to detailing research into contemporary
      treatment options of the condition. These medical treatments range from bile
      salts, rifampicin, and opioid receptor antagonists to antihistamines. Conclusion.
      The burden of pruritus in liver disease patients persists and, although it is a
      common symptom, it can be difficult to manage. In recent years there has been
      greater study into the etiology and treatment of the condition. Nonetheless,
      pruritus remains poorly understood and many patients continue to suffer,
      reiterating the need for further research to improve our understanding of the
      etiology and treatment for the condition. 

PMID- 25861255
TI  - Genome-Wide Expression of MicroRNAs Is Regulated by DNA Methylation in
      Hepatocarcinogenesis.
AB  - Background. Previous studies, including ours, have examined the regulation of
      microRNAs (miRNAs) by DNA methylation, but whether this regulation occurs at a
      genome-wide level in hepatocellular carcinoma (HCC) is unclear. Subjects/Methods.
      Using a two-phase study design, we conducted genome-wide screening for DNA
      methylation and miRNA expression to explore the potential role of methylation
      alterations in miRNAs regulation. Results. We found that expressions of 25 miRNAs
      were statistically significantly different between tumor and nontumor tissues and
      perfectly differentiated HCC tumor from nontumor. Six miRNAs were overexpressed,
      and 19 were repressed in tumors. Among 133 miRNAs with inverse correlations
      between methylation and expression, 8 miRNAs (6%) showed statistically
      significant differences in expression between tumor and nontumor tissues. Six
      miRNAs were validated in 56 additional paired HCC tissues, and significant
      inverse correlations were observed for miR-125b and miR-199a, which is consistent
      with the inactive chromatin pattern found in HepG2 cells. Conclusion. These data
      suggest that the expressions of miR-125b and miR-199a are dramatically regulated
      by DNA hypermethylation that plays a key role in hepatocarcinogenesis. 

PMID- 25861256
TI  - Does the Addition of Cetuximab to Radiochemotherapy Improve Outcome of Patients
      with Locally Advanced Rectal Cancer? Long-Term Results from Phase II Trials.
AB  - Purpose. The addition of cetuximab to radiochemotherapy (RCT) failed to improve
      complete response rates in locally advanced rectal cancer (LARC). We report the
      long-term results in patients treated within two sequential clinical trials.
      Methods. Patients receiving neoadjuvant RCT using capecitabine and irinotecan
      (CapIri) within a phase I/II trial or CapIri + cetuximab within a phase II trial
      were evaluated for analysis of disease-free survival (DFS) and overall survival
      (OS). KRAS exon 2 mutational status had been analyzed in patients receiving
      cetuximab. Results. 37 patients from the CapIri trial and 49 patients from the
      CapIri-cetuximab treatment group were evaluable. Median follow-up time was 75.2
      months. The 5-year DFS rate was 82% (CapIri) and 79% (CapIri-cetuximab) (P =
      0.62). The median OS was 127.4 months. 5-year OS was 73% for both groups (CapIri
      and CapIri-cetuximab) (P = 0.61). No significant difference in DFS (P = 0.86) or
      OS (P = 0.39) was noticed between patients receiving CapIri and those receiving
      CapIri-cetuximab with KRAS wild-type tumors. Conclusions. As the addition of
      cetuximab did not improve neither DFS nor OS it should not play a role in the
      perioperative treatment of patients with LARC, not even of patients with (K)RAS
      WT tumors. 

PMID- 25861257
TI  - Helicobacter pylori Infection Is Associated with an Increased Risk of Hyperemesis
      Gravidarum: A Meta-Analysis.
AB  - Background. Several studies have shown a possible involvement of Helicobacter
      pylori (H. pylori) infection in individuals with hyperemesis gravidarum (HG), but
      the relationship remains controversial. This meta-analysis was performed to
      validate and strengthen the association between HG and H. pylori infection.
      Methods. PubMed, Embase, and Web of Science databases up to March 20, 2014, were
      searched to select studies on the prevalence of H. pylori infection between
      pregnant women with HG and the normal pregnant control subjects. Results. Of the
      HG cases, 1289 (69.6%) were H. pylori-positive; however, 1045 (46.2%) were H.
      pylori-positive in control group. Compared to the non-HG normal pregnant
      controls, infection rate of H. pylori was significantly higher in pregnant women
      with HG (OR = 3.34, 95% CI: 2.32-4.81, P < 0.001). Subgroup analysis indicated
      that H. pylori infection was a risk factor of HG in Asia, Africa, and Oceania,
      especially in Africa (OR = 12.38, 95% CI: 7.12-21.54, P < 0.001). Conclusions. H.
      pylori should be considered one of the risk factors of HG, especially in the
      developing countries. H. pylori eradication could be considered to relieve the
      symptoms of HG in some intractable cases. 

PMID- 25861258
TI  - Association between Helicobacter pylori Infection and Chronic Urticaria: A Meta
      Analysis.
AB  - Background. Some studies have shown the possible involvement of Helicobacter
      pylori (H. pylori) infection in chronic urticaria, but the relationship remains
      controversial. The aim of this meta-analysis was to quantitatively assess the
      association between H. pylori infection and chronic urticaria. Methods.
      Observational studies comparing the prevalence of H. pylori infection in patients
      with chronic urticaria and control subjects were identified through a systematic
      search in MEDLINE and EMBASE up to July 2014. H. pylori infection was confirmed
      by serological or nonserological tests. For subgroup analyses, studies were
      separated by region, publication year, and H. pylori detection method to screen
      the potential factors resulting in heterogeneity. Results. 16 studies involving
      965 CU cases and 1235 controls were included. Overall, the prevalence of H.
      pylori infection was higher in urticarial patients than in controls (OR = 1.66;
      95% CI: 1.12-2.45; P = 0.01). This result persisted in subanalysis of nine high
      quality studies (OR = 1.36; 95% CI: 1.03-1.80; P = 0.03). Subgroup analysis
      showed that detection method of H. pylori is also a potential influential factor
      for the overall results. Conclusions. Our present meta-analysis suggests that H.
      pylori infection is significantly, though weakly, associated with an increased
      risk of chronic urticaria. 

PMID- 25861259
TI  - Myoxinol (Hydrolyzed Hibiscus esculentus Extract) in the Cure of Chronic Anal
      Fissure: Early Clinical and Functional Outcomes.
AB  - Objective. This study was designed to evaluate the early results of the topical
      application of Hydrolyzed Hibiscus esculentus Extract 3% ointment (Myoxinol 3%),
      a novel local product with Botox-like activity, in the conservative treatment of
      chronic anal fissure (CAF). Methods. Among all patients with CAF observed during
      the study period, 31 subjects met the inclusion criteria and underwent medical
      therapy with Myoxinol 3% ointment every 12 hours for 6 weeks. Two patients were
      lost to follow-up. Clinical and manometric follow-up was carried out eight weeks
      after treatment. Results. At follow-up the success rate was 72.4% (21/29); median
      VAS score and mean anal resting pressure were significantly lower if compared
      with respective baseline data. The only one adverse effect of the topical
      application of Myoxinol 3% ointment was perianal itch, which was reported by 3,4%
      (1/29) of the patients available for the analysis. However, in this case this
      symptom did not cause interruption of the treatment. Conclusions. The topical
      application of Myoxinol 3% ointment in the cure of CAF shows encouraging early
      results. Further researches with a larger series and a longer follow-up are
      needed to confirm these data. 

PMID- 25861260
TI  - 24-Hour Measurement of Gastric pH in Rural South Africa.
AB  - Background. Previous studies have established norms of 24-hour gastric pH
      profiles for western countries. This study was designed to establish the pattern
      for a rural African population with a high incidence of oesophageal cancer.
      Methods. After lower oesophageal manometry a probe was placed 10 cm distal to the
      lower oesophageal sphincter. We carried out 24-hour ambulatory monitoring of
      gastric pH on 59 healthy subjects. This was satisfactorily completed on 26 female
      and 18 male (age 21-64, median 35) subjects in the Transkei region of South
      Africa. Results. The mean 24 hour gastric pH was 2.84 and the mean night-time pH
      was 3.7. 40 volunteers recorded a night-time pH reaching over 4. 33 volunteers
      recorded a night-time pH over 7. Night-time alkalinisation was present for 136.4
      minutes (25th centile 22.8, 75th centile 208.1) at pH4 or over, and 79.3 (2.5,
      122.7) minutes at pH7 or over. Episodes of rapid alkaline rise were 17 (10, 47).
      21.1% of these occurred while supine. 35 of 36 tested subjects were positive for
      H. pylori IgG. Conclusion. Gastric alkalinisation is common in Transkei, at a
      higher pH than that reported in other studies, and is sustained longer. Nighttime
      alkalinisation is frequent. This suggests a high level of duodenogastric reflux. 

PMID- 25861261
TI  - Dynamic versus Adynamic Graciloplasty in Treatment of End-Stage Fecal
      Incontinence: Is the Implantation of the Pacemaker Really Necessary? 12-Month
      Follow-Up in a Clinical, Physiological, and Functional Study.
AB  - Purpose. The aim of the study is to compare functional results of end-stage fecal
      incontinence treatment with dynamic graciloplasty and adynamic graciloplasty
      augmented with transanal conditioning of the transposed muscle. Methods. A total
      of 20 patients were qualified for graciloplasty procedure due to end-stage fecal
      incontinence. 7 patients underwent dynamic graciloplasty (DGP), whereas 13
      patients were treated with adynamic graciloplasty, with transanal stimulation in
      the postoperative period (AGP). Clinical, functional, and quality of life
      assessments were performed 3, 6, and 12 months after the procedures. Results.
      There were no intraoperative or early postoperative complications. The detachment
      of gracilis muscle tendon was observed in one patient in DGP group and two in AGP
      group. There was a significant improvement of Fecal Incontinence Quality of Life
      (FIQL) and Fecal Incontinence Severity Index (FISI) scores in both groups 12
      months after procedure. Anorectal manometry showed improvement regarding basal
      and squeeze pressures in both groups, with significantly better squeeze pressures
      in AGP group. Conclusions. The functional effects in the DGP and AGP groups were
      similar. Significantly lower price of the procedure and avoidance of implant
      related complication risk suggest the attractiveness of the AGP method augmented
      by transanal stimulation. 

PMID- 25861262
TI  - Is There Any Advantage of Treating Partners in Helicobacter pylori Eradication?
AB  - Aim. We designed this trial to find answers to the following questions. (1) Does
      the success rate decrease in a country where HP prevalence is high? (2) Can we
      provide benefit by simultaneously treating the partners of infected patients?
      Materials and Methods. The first group consisted of 102 HP-positive patients, and
      both the patients and their HP-positive partners were treated. The second group
      consisted of 104 HP-positive patients whose partners were HP-positive but only
      the patients were treated. The participants in both groups were treated with
      levofloxacin 500 mg daily, amoxicillin 1 g b.i.d, and lansoprazole 30 mg b.i.d
      (LAL) for ten days. Results. In the per-protocol analysis, the eradication
      success rate was found to be 92.2% (94/8) in the first group and 90.4% (94/10) in
      the second group. No statistically significant difference was found between the
      two groups (P > 0.05). Conclusions. With regard to the HP eradication rate, no
      difference was found between treating the HP-positive partners of HP-positive
      patients simultaneously and not treating them simultaneously. According to these
      results, we can say that reinfections between partners do not significantly
      contribute to the failure of eradication. 

PMID- 25861263
TI  - Transplantation of autologous mesenchymal stem cells for end-stage liver
      cirrhosis: a meta-analysis based on seven controlled trials.
AB  - Background. The bone marrow-derived mesenchymal stem cells (BM-MSCs) have
      demonstrated great potential as regenerative medicine in different therapeutic
      applications. This study aims to pool previous controlled clinical trials to make
      an update assessment of the effectiveness of BM-MSC transplantation on end-stage
      liver cirrhosis. Methods. Relevant studies published between January 1990 and
      June 2014 were searched among Pubmed, Embase, and ClinicalTrial.gov. A meta
      analysis was performed to assess the effect of BM-MSCs on liver function
      indicators, including Models of End-Stage Liver Disease (MELD) score, serum
      albumin (g/L), total bilirubin (mg/dl), Prothrombin concentration (%), and
      alanine aminotransferase (ALT) (U/L). Results. BM-MSCs therapy could
      significantly improve liver function in patients with end-stage liver cirrhosis,
      in terms of MELD score, serum albumin, total bilirubin, and prothrombin
      concentration, at least during the half year after transplantation. Conclusions.
      Due to BM-MSCs' immunomodulatory functions and the potential to differentiate
      into hepatocytes, they are a promising therapeutic agent to liver cirrhosis.
      Considering currently available evidence, this therapy is relatively safe and
      effective in improving liver function. However, how different variables should be
      controlled to optimize the therapeutic effect is still not clear. Thus, future
      mechanism studies and clinical trials are required for this optimization. 

PMID- 25861264
TI  - A new metabolism-related index correlates with the degree of liver fibrosis in
      hepatitis C virus-positive patients.
AB  - Background. Only a few biomarkers based on metabolic parameters for evaluating
      liver fibrosis have been reported. The aim of this study was to investigate the
      relevance of an index obtained from three metabolic variables (glycated albumin:
      GA, glycated hemoglobin: HbA1c, and branched-chain amino acids to tyrosine ratio:
      BTR) to the degree of liver fibrosis in hepatitis C virus virus- (HCV-) positive
      patients. Methods. A total of 394 HCV-positive patients were assessed based on
      the values of a new index (GA/HbA1c/BTR). The index findings were used to
      investigate the relationship with the degree of liver fibrosis. Results. The new
      index showed an association with the stage of fibrosis (METAVIR scores: F0-1:
      0.42 +/- 0.10, F2: 0.48 +/- 0.15, F3: 0.56 +/- 0.22, and F4: 0.71 +/- 0.30). The
      index was negatively correlated with three variables of liver function: the
      prothrombin time percentage (P < 0.0001), albumin level (P < 0.0001), and
      cholinesterase level (P < 0.0001). The new index showed a higher correlation
      related to liver function than FIB-4 and the APRI did. In addition, the index
      showed a higher AUROC value than that of FIB-4 and the APRI for prediction of
      liver cirrhosis. Conclusion. The new metabolism-related index, GA/HbA1c/BTR
      value, is shown to relate to the degree of liver fibrosis in HCV-positive
      patients. 

PMID- 25861265
TI  - Abnormal Expression of DNA Double-Strand Breaks Related Genes, ATM and GammaH2AX,
      in Thyroid Carcinoma.
AB  - ATM and gammaH2AX play a vital role in the detection of DNA double-strand breaks
      (DSB) and DNA damage response (DDR). This study aims to investigate ATM and
      gammaH2AX expression in thyroid cancer and discuss possible relationship between
      thyroid function tests and DNA damage. The expression of ATM and gammaH2AX was
      detected by immunohistochemistry in 30 cases of benign nodular goiter, 110 cases
      of well differentiated thyroid cancer, 22 cases of poorly differentiated thyroid
      cancer, and 21 cases of anaplastic thyroid cancer. Clinicopathological features,
      including differentiation stages, distant metastasis, lymph node metastasis, T
      classification, TNM stage, and tests of thyroid functions (TPOAb, Tg Ab, T3, FT3,
      T4, FT4, TSH, and Tg), were reviewed and their associations with gammaH2AX and
      ATM were analyzed. gammaH2AX and ATM expressed higher in thyroid cancer tissues
      than in benign nodular goiter and normal adjacent tissues. gammaH2AX was
      correlated with ATM in thyroid cancer. Both gammaH2AX and ATM expression were
      associated with FT3. gammaH2AX was also associated with T classification, TNM
      stage, FT4, TSH, and differentiation status. Therefore both of ATM and gammaH2AX
      seem to correlate with thyroid hormones and gammaH2AX plays a role in the
      differentiation status of thyroid cancer. 

PMID- 25861267
TI  - Decreased Expression of GPER1 Gene and Protein in Goiter.
AB  - Goiter is more common in women, suggesting that estrogen could be involved in its
      physiopathology. The presence of classical estrogen receptors (ERalpha and
      ERbeta) has been described in thyroid tissue, suggesting a direct effect of
      estrogen on the gland. A nonclassic estrogen receptor, the G-protein-coupled
      estrogen receptor (GPER1), has been described recently in several tissues.
      However, in goiter, the presence of this receptor has not been studied yet. We
      investigated GPER1 gene and protein expressions in normal thyroid and goiter
      using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and
      Western blot, respectively. In normal thyroid (n = 16) and goiter (n = 19), GPER1
      gene was expressed in all samples, while GPER1 protein was expressed in all
      samples of normal thyroid (n = 15) but in only 72% of goiter samples (n = 13).
      When comparing GPER1 gene and protein levels in both conditions, gene expression
      and protein levels were higher in normal thyroid than in goiter, suggesting a
      role of this receptor in this condition. Further studies are needed to elucidate
      the role of GPER1 in normal thyroid and goiter. 

PMID- 25861266
TI  - The impact of sleep and circadian disturbance on hormones and metabolism.
AB  - The levels of several hormones fluctuate according to the light and dark cycle
      and are also affected by sleep, feeding, and general behavior. The regulation and
      metabolism of several hormones are influenced by interactions between the effects
      of sleep and the intrinsic circadian system; growth hormone, melatonin, cortisol,
      leptin, and ghrelin levels are highly correlated with sleep and circadian
      rhythmicity. There are also endogenous circadian mechanisms that serve to
      regulate glucose metabolism and similar rhythms pertaining to lipid metabolism,
      regulated through the actions of various clock genes. Sleep disturbance, which
      negatively impacts hormonal rhythms and metabolism, is also associated with
      obesity, insulin insensitivity, diabetes, hormonal imbalance, and appetite
      dysregulation. Circadian disruption, typically induced by shift work, may
      negatively impact health due to impaired glucose and lipid homeostasis, reversed
      melatonin and cortisol rhythms, and loss of clock gene rhythmicity. 

PMID- 25861268
TI  - Application of berberine on treating type 2 diabetes mellitus.
AB  - Traditional Chinese medicine (TCM) performs a good clinical practice and is
      showing a bright future in the treatment of diabetes mellitus (DM). TCM treatment
      has certain advantages of less toxicity and/or side effects, and herbs could
      provide multiple therapeutic effects. Berberine (BBR) is a classical natural
      medicine. In this review, we summarize the application of BBR in the treatment of
      DM from two aspects. First, modern pharmacological effects of BBR on glucose
      metabolism are summarized, such as improving insulin resistance, promoting
      insulin secretion, inhibiting gluconeogenesis in liver, stimulating glycolysis in
      peripheral tissue cells, modulating gut microbiota, reducing intestinal
      absorption of glucose, and regulating lipid metabolism. BBR is used to treat
      diabetic nephropathy (DPN), diabetic neuropathy (DN), and diabetic cardiomyopathy
      due to its antioxidant and anti-inflammatory activities. Second, the clinical
      application of BBR is reviewed, such as listing some clinical trials on the
      effectiveness and safety of BBR, explaining applicable stage and syndrome, the
      reasonable dose and dose formulation, and the toxicity and/or side effects. This
      review provides scientific evidence about BBR, as well as introducing some
      traditional Chinese medical theory and clinical experience, in order to guide
      clinician to use BBR more suitably and reasonably. 

PMID- 25861269
TI  - Expression analysis of gnrh1 and gnrhr1 in spermatogenic cells of rat.
AB  - Hypothalamic Gonadotropin Releasing Hormone (GnRH), via GnRH receptor (GnRHR), is
      the main actor in the control of reproduction, in that it induces the
      biosynthesis and the release of pituitary gonadotropins, which in turn promote
      steroidogenesis and gametogenesis in both sexes. Extrabrain functions of GnRH
      have been extensively described in the past decades and, in males, local GnRH
      activity promotes the progression of spermatogenesis and sperm functions at
      several levels. The canonical localization of Gnrh1 and Gnrhr1 mRNA is Sertoli
      and Leydig cells, respectively, but ligand and receptor are also expressed in
      germ cells. Here, we analysed the expression rate of Gnrh1 and Gnrhr1 in rat
      testis (180 days old) by quantitative real-time PCR (qPCR) and by in situ
      hybridization we localized Gnrh1 and Gnrhr1 mRNA in different spermatogenic cells
      of adult animals. Our data confirm the testicular expression of Gnrh1 and of
      Gnrhr1 in somatic cells and provide evidence that their expression in the
      germinal compartment is restricted to haploid cells. In addition, not only
      Sertoli cells connected to spermatids in the last steps of maturation but also
      Leydig and peritubular myoid cells express Gnrh1. 

PMID- 25861270
TI  - Esculetin Downregulates the Expression of AML1-ETO and C-Kit in Kasumi-1 Cell
      Line by Decreasing Half-Life of mRNA.
AB  - One of the most frequent genetic aberrations in acute myeloid leukemia (AML) is
      chromosomal translocation between AML1/RUNX1 on chromosome 21 and ETO gene on
      chromosome 8 resulting in the expression of chimeric oncogene AML1-ETO. Although
      patients with t(8;21) translocation have good prognosis, 5-year survival is
      observed only in 50% of the cases. AML1-ETO translocation is usually accompanied
      by overexpression of mutant C-Kit, a tyrosine kinase, which contributes to
      uncontrolled proliferation of premature blood cells leading to relapse and poor
      prognosis. We illustrate the potential use of esculetin on leukemic cell line,
      Kasumi-1, bearing t(8;21) translocation and mutated C-Kit gene. Esculetin
      decreases the expression of AML1-ETO at both protein and transcript level within
      24 hours of treatment. Half-life of AML1-ETO mRNA was reduced from 7 hours to 1.5
      hours. Similarly half-life of C-Kit mRNA was reduced to 2 hours from 5 hours in
      esculetin treated cells. Esculetin also perturbed the expression of ectopically
      expressed AML1-ETO in U937 cells. The decreased expression of AML1-ETO chimeric
      gene was associated with increased expression of LAT1 and RUNX3 genes, targets of
      AML1. We envisage that discovery of a drug candidate which could target both
      these mutated genes would be a considerable breakthrough for future application. 

PMID- 25861271
TI  - Quantitative Analysis of Salivary TNF-alpha in Oral Lichen Planus Patients.
AB  - Objective. The aim of this study was to quantitatively evaluate the salivary
      tumor necrosis factor-alpha (TNF-alpha) level in oral lichen planus patients and
      to compare the levels of TNF-alpha between saliva and serum of OLP and controls.
      Methods. Serum and whole saliva from 30 patients with active lesions of oral
      lichen planus (OLP) and 30 healthy persons were investigated for the presence of
      TNF-alpha by enzyme immunoassay. Student's independent t-test and two-sample
      binomial proportion test were used to calculate significance of the mean values
      of TNF-alpha in serum and saliva and to determine the proportions of the detected
      and nondetected samples in both groups. Results. Proportion of detection and the
      mean of detectability between saliva and serum of Group B show an almost equal
      value, which suggests that saliva can be a good alternate to serum to analyze TNF
      alpha in oral lichen planus patients. 

PMID- 25861272
TI  - A study of success rate of miniscrew implants as temporary anchorage devices in
      singapore.
AB  - Objective. To find out the success rate of miniscrew implants in the National
      Dental Centre of Singapore (NDCS) and the impact of patient-related, location
      related, and miniscrew implant-related factors. Materials and Methods. Two
      hundred and eighty-five orthodontic miniscrew implants were examined from NDCS
      patient records. Eleven variables were analysed to see if there is any
      association with success. Outcome was measured twice, immediately after surgery
      prior to orthodontic loading (T1) and 12 months after surgery (T2). The outcome
      at T2 was assessed 12 months after the miniscrew's insertion date or after its
      use as a temporary anchorage device has ceased. Results. Overall success rate was
      94.7% at T1 and 83.3% at T2. Multivariate analysis revealed only the length of
      miniscrew implant to be significantly associated with success at both T1 (P =
      0.002) and T2 (P = 0.030). Miniscrew implants with lengths of 10-12 mm had the
      highest success rate (98.0%) compared to other lengths, and this is statistically
      significant (P = 0.035). At T2, lengths of 10-12 mm had significantly (P = 0.013)
      higher success rates (93.5%) compared to 6-7 mm (76.7%) and 8 mm (82.1%)
      miniscrew implants. Conclusion. Multivariate statistical analyses of 11 variables
      demonstrate that length of miniscrew implant is significant in determining
      success. 

PMID- 25861273
TI  - Optimization of Ultrasound-Assisted Extraction of Morphine from Capsules of
      Papaver somniferum by Response Surface Methodology.
AB  - In this study, amount of morphine from poppy capsules (Papaver somniferum) was
      investigated using ultrasonic assisted extraction (UAE). Response surface
      methodology was used to estimate effective experimental conditions on the content
      extraction of poppy capsules. For this purpose, solvent/solid ratio (10-20 mL/500
      mg sample), pH (1-13), time (30-60 min), and temperature (30-50 degrees C) were
      chosen as experimental variables. The affected response is extraction recovery
      values for morphine from poppy straw. For interpreting the relationship between
      experimental factors and response, a design table was established with
      combinations of three different concentrations levels of this compound in 29
      trials. The second order quadratic model gave a satisfactory description of the
      experimental data. In our study, R-Squared (0.96), Adj-R-Squared (0.92), and Pred
      R-Squared (0.78) values for extraction yield display good accuracy of the derived
      model. The predicted optimal conditions for the highest morphine level (3.38 mg
      morphine/500 mg-sample) were found at 19.99 mL solvent/500 mg solid ratio, 59.94
      min extraction time, 1.10 pH, and 42.36 degrees C temperature. In the optimal
      extraction conditions, the experimental values are very close to the predicted
      values. Consequently, the response surface modeling can be achieved sufficiently
      to predict extraction yield from poppy straw by ultrasound assisted extraction. 

PMID- 25861274
TI  - Enteropathogens associated with acute diarrhea in children from households with
      high socioeconomic level in uruguay.
AB  - Infectious diarrhea, a common disease of children, deserves permanent monitoring
      in all social groups. To know the etiology and clinical manifestations of acute
      diarrhea in children up to 5 years of age from high socioeconomic level
      households, we conducted a descriptive, microbiological, and clinical study.
      Stools from 59 children with acute community-acquired diarrhea were examined, and
      their parents were interviewed concerning symptoms and signs. Rotavirus,
      adenovirus, and norovirus were detected by commercially available qualitative
      immunochromatographic lateral flow rapid tests. Salmonella, Campylobacter,
      Yersinia, and Shigella were investigated by standard bacteriological methods and
      diarrheagenic E. coli by PCR assays. We identified a potential enteric pathogen
      in 30 children. The most frequent causes of diarrhea were enteropathogenic E.
      coli (EPEC), viruses, Campylobacter, Salmonella, and Shiga-toxin-producing E.
      coli (STEC). Only 2 patients showed mixed infections. Our data suggest that
      children with viral or Campylobacter diarrhea were taken to the hospital earlier
      than those infected with EPEC. One child infected with STEC O26 developed
      "complete" HUS. The microbiological results highlight the importance of zoonotic
      bacteria such as atypical EPEC, Campylobacter, STEC, and Salmonella as pathogens
      associated with acute diarrhea in these children. The findings also reinforce our
      previous communications about the regional importance of non-O157 STEC strains in
      severe infant food-borne diseases. 

PMID- 25861275
TI  - Failure rate of single dose methotrexate in managment of ectopic pregnancy.
AB  - Background. One of the treatment modalities for ectopic pregnancy is
      methotrexate. The purpose of this study is to identify the failure rate of
      methotrexate in treating patients with ectopic pregnancy as well as the risk
      factors leading to treatment failure. Methods. A retrospective chart review of
      225 patients who received methotrexate as a primary management option for ectopic
      pregnancy. Failure of single dose of methotrexate was defined as drop of BHCG
      level less than or equal to 14% in the seventh day after administration of
      methotrexate. Results. 225 patients had methotrexate. Most of the patients (151
      (67%)) received methotrexate based on the following formula: f 50 mg X body
      surface area. Single dose of methotrexate was successful in 72% (162/225) of the
      patients. 28% (63/225) were labeled as failure of single dose of methotrexate
      because of suboptimal drop in BhCG. 63% (40/63) of failure received a second dose
      of methotrexate, and 37% (23/63) underwent surgical treatment. Among patient who
      received initial dose of methotrexate, 71% had moderate or severe pain, and 58%
      had ectopic mass size of more than 4 cm on ultrasound. Conclusion. Liberal use of
      medical treatment of ectopic pregnancy results in 71% success rate. 

PMID- 25861276
TI  - Probable hydrochlorothiazide-induced myopericarditis: first case reported.
AB  - Hydrochlorothiazide has never been reported as a reason for myopericarditis. An
      African American female, with past history of hypertension, coronary artery
      disease, and sulfa allergy, presented with indolent onset and retrosternal chest
      pain which was positional, pleuritic, and unresponsive to sublingual
      nitroglycerin. Her medications included hydrochlorothiazide (HCTZ) which was
      started three months ago for uncontrolled hypertension. Significant laboratory
      parameters included erythrocyte sedimentation rate (ESR) of 47 mm/hr and peak
      troponin of 0.26 ng/mL. Transthoracic echocardiogram (TTE) revealed preserved
      ejection fraction with no segmental wall motion abnormalities; however, it showed
      moderate pericardial effusion without tamponade physiology. We hypothesize that
      this myopericarditis could be due to HCTZ allergic reaction after all other
      common etiologies have been ruled out. There is a scarcity of the literature
      regarding HCTZ as an etiology for pericardial disease, with only one case
      reported as presumed hydrochlorothiazide-induced pericardial effusion. Management
      involves discontinuation of HCTZ and starting anti-inflammatory therapy. 

PMID- 25861277
TI  - Minimal invasive management of anastomosis leakage after colon resection.
AB  - The gold standard of surgical treatment of colorectal anastomotic leak is
      abdominal drainage of collected fluid and stoma formation. Conventional
      laparotomy has been the preferred approach for treatment. However, both
      laparoscopic surgical techniquesand endoscopic stenting have gained popularity
      over the past years as minimal invasive approaches, especially in the management
      and treatment of perforations of the gastrointestinal system. We present here a
      successful treatment with a minimal invasive management of anastomosis leak in
      the early postoperative period after colon resection in a 62-year-old female
      patient who had undergone urgent laparoscopic intra-abdominal lavage and drainage
      followed by endoscopic stenting. 

PMID- 25861278
TI  - A case of the serotonin syndrome secondary to phenelzine monotherapy at
      therapeutic dosing.
AB  - A 27-year-old Caucasian female with a history of depression was admitted to our
      local hospital with vague events that occurred a day before. This included an
      episode of dysarthria, and unsteadiness, followed by feeling generally unwell.
      Two weeks prior to presentation she was commenced on phenelzine. During clinical
      assessment she suddenly deteriorated with a dramatic fall in her conscious level.
      Moreover, she became hyperthermic, tachycardic, and diaphoretic, and developed
      increased tone in all muscles and ocular clonus. Rectal diazepam was administered
      but failed to control the symptoms. Consequently, she was transferred to the
      intensive care unit for intubation and muscle relaxants were commenced. She
      responded well and recovered next day without complications. Her symptoms and
      signs were consistent with the serotonin syndrome with phenelzine being the
      likely cause. To the best of our knowledge, this is the first reported case to
      associate the condition with phenelzine alone at therapeutic dose. 

PMID- 25861279
TI  - The Chondrogenic Induction Potential for Bone Marrow-Derived Stem Cells between
      Autologous Platelet-Rich Plasma and Common Chondrogenic Induction Agents: A
      Preliminary Comparative Study.
AB  - The interests in platelet-rich plasma (PRP) and their application in stem cell
      therapy have contributed to a better understanding of the basic biology of the
      prochondrogenesis effect on bone marrow-derived stem cells (BMSCs). We aimed at
      comparing the effect of autologous PRP with common chondrogenic induction agents
      (CCIAs) on the chondrogenic differentiation of BMSCs. Rabbit BMSCs were isolated
      and characterized by flow cytometry and differentiated towards adipocytes and
      osteoblasts. The chondrogenic response of BMSCs to autologous PRP and CCIAs which
      included transforming growth factor-beta1 (TGF-beta1), dexamethasone (DEX), and
      vitamin C (Vc) was examined by cell pellet culture. The isolated BMSCs after two
      passages highly expressed CD29 and CD44 but minimally expressed CD45. The
      osteogenic and adipogenic differentiation potentials of the isolated BMSCs were
      also confirmed. Compared with common CCIAs, autologous PRP significantly
      upregulated the chondrogenic related gene expression, including Col-2, AGC, and
      Sox-9. Osteogenic related gene expression, including Col-1 and OCN, was not of
      statistical significance between these two groups. Thus, our data shows that,
      compared with common chondrogenic induction agents, autologous PRP can be more
      effective in promoting the chondrogenesis of BMSCs. 

PMID- 25861280
TI  - Development of a xeno-free substrate for human embryonic stem cell growth.
AB  - Traditionally, human embryonic stem cells (hESCs) are cultured on inactivated
      live feeder cells. For clinical application using hESCs, there is a requirement
      to minimize the risk of contamination with animal components. Extracellular
      matrix (ECM) derived from feeder cells is the most natural way to provide xeno
      free substrates for hESC growth. In this study, we optimized the step-by-step
      procedure for ECM processing to develop a xeno-free ECM that supports the growth
      of undifferentiated hESCs. In addition, this newly developed xeno-free substrate
      can be stored at 4 degrees C and is ready to use upon request, which serves as an
      easier way to amplify hESCs for clinical applications. 

PMID- 25861281
TI  - Bone marrow-derived, neural-like cells have the characteristics of neurons to
      protect the peripheral nerve in microenvironment.
AB  - Effective repair of peripheral nerve defects is difficult because of the slow
      growth of new axonal growth. We propose that "neural-like cells" may be useful
      for the protection of peripheral nerve destructions. Such cells should prolong
      the time for the disintegration of spinal nerves, reduce lesions, and improve
      recovery. But the mechanism of neural-like cells in the peripheral nerve is still
      unclear. In this study, bone marrow-derived neural-like cells were used as seed
      cells. The cells were injected into the distal end of severed rabbit peripheral
      nerves that were no longer integrated with the central nervous system.
      Electromyography (EMG), immunohistochemistry, and transmission electron
      microscopy (TEM) were employed to analyze the development of the cells in the
      peripheral nerve environment. The CMAP amplitude appeared during the 5th week
      following surgery, at which time morphological characteristics of myelinated
      nerve fiber formation were observed. Bone marrow-derived neural-like cells could
      protect the disintegration and destruction of the injured peripheral nerve. 

PMID- 25861282
TI  - Sonic hedgehog produced by bone marrow-derived mesenchymal stromal cells supports
      cell survival in myelodysplastic syndrome.
AB  - The role of marrow microenvironment in the pathogenesis of myelodysplastic
      syndrome (MDS) remains controversial. Therefore, we studied the influence of bone
      marrow-derived mesenchymal stromal cells (BMSCs) from patients with different
      risk types of MDS on the survival of the MDS cell lines SKM-1 and MUTZ-1. We
      first demonstrated that the expression of Sonic hedgehog (Shh), smoothened (Smo),
      and glioma-associated oncogene homolog 1 (Gli1) was increased in MDS patients (n
      = 23); the increase in expression was positively correlated with the presence of
      high-risk factors. The Shh signaling inhibitor, cyclopamine, inhibited high-risk
      MDS BMSC-induced survival of SKM-1 and MUTZ-1 cells, suggesting a role for Shh
      signaling in MDS cell survival. Furthermore, cyclopamine-mediated inhibition of
      Shh signaling in SKM-1 and MUTZ-1 cells resulted in decreased DNMT1 expression
      and cell survival; however, exogenous Shh peptide had the opposite effect,
      suggesting that Shh signaling could regulate the expression of DNMT1, thereby
      modulating cell survival in MDS. In addition, the apoptosis of SKM-1 and MUTZ-1
      cell increased significantly when cultured with cyclopamine and a demethylation
      agent, 5-Aza-2'-deoxycytidine. These findings suggest that Shh signaling from
      BMSCs is important in the pathogenesis of MDS and could play a role in disease
      progression by modulating methylation. 

PMID- 25861284
TI  - Posttransfusion haematocrit equilibration: timing posttransfusion haematocrit
      check in neonates at the national hospital, abuja, Nigeria.
AB  - Anaemia is a common morbidity in the NICU and often requires transfusion of
      packed red blood cells. Haematocrit equilibration following red cell transfusion
      occurs over time ultimately resulting in a stable packed cell volume (PCV).
      Knowledge of this equilibration process is pertinent in the accurate timing of
      posttransfusion (PT) PCV. We conducted a prospective study to determine an
      appropriate timing for PT PCV estimation on 47 stable anaemic babies at the
      Neonatal Unit of National Hospital, Abuja. Values of PCV were determined before
      transfusion and at 1, 6, 12, 24, and 48 hours posttransfusion. Forty of the
      recruited neonates and young infants were analyzed. Their gestational age range
      was 26 to 40 weeks. 1-hour PT PCV (48.5% +/- 5.5%) was similar to the 6-hour PT
      PCV (47.8% +/- 5.6%) P = 0.516, but both were significantly different from the 12
      hour (46.8% +/- 5.9%), 24-hour (45.9 +/- 5.8%), and 48-hour (45.4% +/- 6.2%) PT
      PCVs. The 12-hour PT PCV was similar to the 24-hour and 48-hour PT PCVs (P =
      0.237 and 0.063, resp.). We concluded that, in stable nonhaemorrhaging and
      nonhaemolysing young infants, the estimated timing of haematocrit equilibration
      and, consequently, posttransfusion PCV is 12 hours after red blood cell
      transfusion. 

PMID- 25861285
TI  - Enteral L-Arginine and Glutamine Supplementation for Prevention of NEC in Preterm
      Neonates.
AB  - Objective. Evaluating the efficacy and safety of arginine and glutamine
      supplementation in decreasing the incidence of NEC among preterm neonates.
      Methods. Prospective case-control study done on 75 preterm neonates <=34 weeks,
      divided equally into L-arginine group receiving enteral L-arginine, glutamine
      group receiving enteral glutamine, and control group. Serum L-arginine and
      glutamine levels were measured at time of enrollment (sample 1), after 14 days of
      enrollment (sample 2), and at time of diagnosis of NEC (sample 3). Results. The
      incidence of NEC was 9.3%. There was no difference in the frequency of NEC
      between L-arginine and control groups (P > 0.05). NEC was not detected in
      glutamine group; L-arginine concentrations were significantly lower in arginine
      group than control group in both samples while glutamine concentrations were
      comparable in glutamine and control groups in both samples. No significant
      difference was found between groups as regards number of septic episodes,
      duration to reach full oral intake, or duration of hospital stay. Conclusion.
      Enteral L-arginine supplementation did not seem to reduce the incidence of NEC.
      Enteral glutamine may have a preventive role against NEC if supplied early to
      preterm neonates. However, larger studies are needed to confirm these findings.
      This work is registered in ClinicalTrials.gov (ClinicalTrials.gov Identifier:
      NCT01263041). 

PMID- 25861283
TI  - Periodontal ligament stem cells: current status, concerns, and future prospects.
AB  - Periodontal ligament stem cells (PDLSCs), which reside in the perivascular space
      of the periodontium, possess characteristics of mesenchymal stem cells and are a
      promising tool for periodontal regeneration. Recently, great progress has been
      made in PDLSC transplantation. Investigators are attempting to maximize the
      proliferation and differentiation potential of PDLSCs by modifying culture
      conditions and applying growth factors. Nevertheless, problems remain. First,
      incomparability among different studies must be minimized by establishing
      standard guidelines for culture and identification of PDLSCs. Notably, attention
      should be paid to the biological safety of PDLSC transplantation. The present
      review updates the latest findings regarding PDLSCs and discusses standard
      criteria for culture and identification of PDLSCs. Finally, the review calls for
      careful consideration of PDLSC transplantation safety. 

PMID- 25861287
TI  - Obesity. An analysis of epidemiological and prognostic research.
AB  - INTRODUCTION: Apart from its medical dimension, the current problem with obesity
      has acquired social urgency. This serious lifestyle disease has a negative impact
      on a number of life processes in the body, causing distortions and damaging
      different structures. It also contributes to clinical complications, lowers the
      quality of life and reduces life expectancy. Apart from health-related
      consequences, it can bring such unfavourable results as social, mental and
      emotional disorders. MATERIAL AND METHODS: A systematic review of relevant
      epidemiological studies on obesity in Poland relative to selected countries in
      Europe and the world over the past 15 years was conducted. Also an attempt was
      made at forecasting the development of the obesity problem. RESULTS: The analysed
      results demonstrated that the percentage of obese people among the adult
      population of Poland was on the rise in the period under investigation. Taking
      into account the estimated growth rate, we can assume that the percentage of
      obese people in Poland right now might total 23.7% for men and 23.3% for women.
      If no changes are introduced in this respect, in 2020 we can expect a rise to,
      respectively, 30.3% and 27.3%, and in 2030 to 37% for men and 31.4% for women.
      CONCLUSIONS: The increase in the percentage of obese people among the adult
      population in Poland is most likely connected with a positive energy balance. In
      comparison to other European countries Poland has the highest percentage of obese
      men and women.

PMID- 25861288
TI  - Clinical efficacy and safety of colistin treatment in patients with pulmonary
      infection caused by Pseudomonas aeruginosa or Acinetobacter baumannii: a meta
      analysis.
AB  - INTRODUCTION: The aim of this study was to evaluate the efficacy and safety of
      colistin treatment in patients with pulmonary infection caused by Pseudomonas
      aeruginosa or Acinetobacter baumannii. MATERIAL AND METHODS: The relevant studies
      were identified through a search of public databases including PubMed, MEDLINE
      and EMBASE up to December 2012. A meta-analysis was conducted to compare the
      clinical response, mortality and renal damage of colistin (colistin group) versus
      other effective antibiotics (control group). The odds ratio (OR) was chosen as
      the effect size. RESULTS: A total of 9 studies were eventually identified. The
      result of the meta-analysis showed that the pooled OR of clinical response was
      1.24 (95% CI = 0.68-2.27, p > 0.05) for patients in the colistin group versus the
      control group, indicating no significant difference in efficacy between colistin
      and control groups. Similar results were obtained by the further subgroup meta
      analyses by sample size, research year, ethnicity and study method. Treatment
      with colistin versus other agents did not affect hospital mortality (OR = 1.05,
      95% CI = 0.58-1.89, p > 0.05) or renal damage (OR = 1.25, 95% CI = 0.78-2.00, p >
      0.05). The combined estimate of our analysis was strong across multiple
      sensitivity analyses and without significant publication bias. CONCLUSIONS: Our
      results suggest that colistin may be as efficacious and safe as standard
      antibiotics for the treatment of pulmonary infection.

PMID- 25861286
TI  - Statin intolerance - an attempt at a unified definition. Position paper from an
      International Lipid Expert Panel.
AB  - Statins are one of the most commonly prescribed drugs in clinical practice. They
      are usually well tolerated and effectively prevent cardiovascular events. Most
      adverse effects associated with statin therapy are muscle-related. The recent
      statement of the European Atherosclerosis Society (EAS) has focused on statin
      associated muscle symptoms (SAMS), and avoided the use of the term 'statin
      intolerance'. Although muscle syndromes are the most common adverse effects
      observed after statin therapy, excluding other side effects might underestimate
      the number of patients with statin intolerance, which might be observed in 10-15%
      of patients. In clinical practice, statin intolerance limits effective treatment
      of patients at risk of, or with, cardiovascular disease. Knowledge of the most
      common adverse effects of statin therapy that might cause statin intolerance and
      the clear definition of this phenomenon is crucial to effectively treat patients
      with lipid disorders. Therefore, the aim of this position paper was to suggest a
      unified definition of statin intolerance, and to complement the recent EAS
      statement on SAMS, where the pathophysiology, diagnosis and the management were
      comprehensively presented. 

PMID- 25861289
TI  - Lipid-lowering therapy in older persons.
AB  - Numerous randomized, double-blind, placebo-controlled studies and observational
      studies have shown that statins reduce mortality and major cardiovascular events
      in older high-risk persons with hypercholesterolemia. The Heart Protection Study
      showed that statins reduced mortality and major cardiovascular events in high
      risk persons regardless of the initial level of serum lipids, age, or gender. The
      updated National Cholesterol Education Program III guidelines state that in very
      high-risk persons, a serum low-density lipoprotein (LDL) cholesterol level of <
      70 mg/dl (1.8 mmol/l) is a reasonable clinical strategy for moderately high-risk
      persons (2 or more risk factors and a 10-year risk for coronary artery disease of
      10% to 20%), and the serum LDL cholesterol should be reduced to < 100 mg/dl (2.6
      mmol/l). When LDL cholesterol-lowering drug therapy is used to treat high-risk
      persons or moderately high-risk persons, the serum LDL cholesterol should be
      reduced by at least 30% to 40%. The serum LDL cholesterol should be decreased to
      less than 160 mg/dl in persons at low risk for cardiovascular disease. Addition
      of other lipid-lowering drugs to statin therapy has not been demonstrated to
      further reduce cardiovascular events and mortality. 

PMID- 25861290
TI  - Platelet-derived growth factors induced lymphangiogenesis: evidence, unanswered
      questions and upcoming challenges.
AB  - Crosstalk between angiogenesis and lymphangiogenesis in embryonic development
      continues during postnatal life and has specific mechanisms involving factors
      that initiate activation of the intracellular cascade for their specific
      receptors. Platelet-derived growth factors (PDGFs) and their corresponding
      receptors (PDGFRs) are known as important regulators of blood vessel development
      in both normal and pathologic angiogenesis. Despite some recent papers which
      reported a potential role of the PDGF/PDGFR axis in lymphatic spread of tumor
      cells, a few papers have suggested the potential role of PDGFs in tumor
      lymphangiogenesis development. The present paper summarizes the potential
      lymphangiogenic role of the PDGF/PDGFR axis, underlying upcoming challenges in
      the field. 

PMID- 25861292
TI  - Textural entropy as a potential feature for quantitative assessment of jaw bone
      healing process.
AB  - INTRODUCTION: The aim of the study was to propose and evaluate textural entropy
      as a parameter for bone healing assessment. MATERIAL AND METHODS: One hundred and
      twenty radiographs with loss of bone architecture were investigated (a bone
      defect was circumscribed - ROI DEF). A reference region (ROI REF) of the same
      surface area as the ROI DEF was placed in a field distant from the defect, where
      a normal, trabecular pattern of bone structure was well visualized. Data of three
      time points were investigated: T0 - immediately after the surgical procedure, T1 
      3 months post-op, and T2 - 12 months post-op. RESULTS: Textural entropy as a
      parameter describing bone structure regeneration was selected based on Fisher
      coefficient (F) evaluation. F was highest in T0 (3.4) and was decreasing later in
      T1 (1.7) and T2 (1.0 - means final lack of difference in the structure to
      reference bone). Textural entropy is a measure of structure disarrangement which
      in a bone defect region attains minimal value due to structural homogeneity, i.e.
      low complexity of the texture. The calculated parameter in the investigated
      material revealed a gradual increase inside the bone defect (p < 0.05), i.e.
      increase of complexity in a time-dependent manner starting from immediate post-op
      (T0 = 2.51; T1 = 2.68) up to most complex 1 year post-operational (T2 = 2.73),
      reaching the reference level of a normal bone. CONCLUSIONS: Textural entropy may
      be useful for computer assisted evaluation of bone regeneration process. The
      complexity of the texture corresponds to mature trabecular bone formation.

PMID- 25861291
TI  - Urinary tract infections in pregnancy: old and new unresolved diagnostic and
      therapeutic problems.
AB  - Urinary tract infections (UTIs) are common in pregnant women and pose a great
      therapeutic challenge, since the risk of serious complications in both the mother
      and her child is high. Pregnancy is a state associated with physiological,
      structural and functional urinary tract changes which promote ascending
      infections from the urethra. Unlike the general population, all pregnant women
      should be screened for bacteriuria with urine culture, and asymptomatic
      bacteriuria must be treated in every case that is diagnosed, as it is an
      important risk factor for pyelonephritis in this population. The antibiotic
      chosen should have a good maternal and fetal safety profile. In this paper,
      current principles of diagnosis and management of UTI in pregnancy are reviewed,
      and the main problems and controversies are identified and discussed. 

PMID- 25861293
TI  - Blood pressure control predicts plasma matrix metalloproteinase-9 in diabetes
      mellitus type II.
AB  - INTRODUCTION: Matrix metalloproteinase-9 (MMP-9) plays an important role in
      extracellular and vascular remodelling. We aimed therefore to assess the role of
      blood pressure (BP) control on plasma MMP-9 in relation to the presence of
      diabetes mellitus (DM) type II. MATERIAL AND METHODS: Plasma MMP-9 was measured
      in 61 patients who were divided into two groups depending on their BP control as
      follows: 49 patients with uncontrolled arterial hypertension (AH) defined as BP
      values > 130/80 mm Hg and 12 patients with optimal blood pressure values. Plasma
      MMP-9 levels were measured with immunoassay at discharge. Group comparisons were
      made with the independent t-test, Mann-Whitney U-test and chi(2) test where
      appropriate. The associations of the variables with MMP-9 were investigated with
      linear regression analyses. RESULTS: The diabetics made up 34.4% of the
      investigated patients. Frequency of DM did not differ between the two BP groups
      (30.0% vs. 36.6%, p > 0.05). Plasma MMP-9 concentrations differed significantly
      between the diabetics vs. non-diabetics (median: 1.9 ng/ml, range: 1.0-7.3 vs.
      1.4 ng/ml, range: 0.5-4.7, p < 0.05). Stratification across the categories of BP
      control showed a significant correlation between plasma MMP-9 and DM type II only
      in the uncontrolled BP group. The significance of that relationship disappeared
      in the group of patients with optimal BP control. CONCLUSIONS: Plasma values of
      MMP-9 are raised in patients with DM type II. The results revealed the impact of
      the combination of uncontrolled AH and DM type II on vascular remodelling
      processes.

PMID- 25861294
TI  - Indicators of the metabolic syndrome in obese adolescents.
AB  - INTRODUCTION: To assess the prevalence of metabolic risk indicators for the
      metabolic syndrome (MS) in a sample of obese Egyptian adolescents and to compare
      anthropometric and biochemical parameters in subjects with one or two parameters
      of the MS with those who meet MS criteria. MATERIAL AND METHODS: A descriptive,
      cross-sectional study was conducted on 300 obese adolescents, with a mean age of
      15.45 +/-2.54 years. Variables examined included body mass index (BMI), waist
      circumference (WC), waist to hip ratio (WHR), systolic and diastolic blood
      pressure (BP), fasting blood glucose, cholesterol, triglycerides (TG), high
      density lipoprotein (HDL), low-density lipoproteins (LDL), insulin and insulin
      resistance (IR) measured by Homeostasis Model Assessment-Insulin Resistance (HOMA
      IR). Receiver operating characteristic (ROC) curve analysis was used to determine
      the predictive powers of anthropometric parameters associated with increased risk
      for the MS. RESULTS: The overall prevalence of the MS was 20%. Individuals
      meeting 3 or more MS criteria had significantly higher levels of BP, TG, glucose,
      insulin and HOMA-R and low HDL levels compared with those who had 1 or 2 MS
      criteria. Area under the curve (AUC) for identifying the MS risk factors was the
      highest for WHR, followed by WC and BMI in both genders (p < 0.001). CONCLUSIONS:
      The most prevalent metabolic risk factors that compose the MS were arterial
      hypertension, low HDL and hypertriglyceridemia; BMI tended to be the weakest
      index for identifying MS risk factors, while WHR was the best predictive index in
      both genders.

PMID- 25861295
TI  - Evaluation of T-wave alternans in high-resolution ECG maps recorded during the
      stress test in patients after myocardial infarction.
AB  - INTRODUCTION: Recent studies point to analysis of T-wave alternans as a promising
      indicator of an increased risk of life-threatening ventricular arrhythmias. In
      this study the occurrence of T-wave alternans in the high-resolution ECGs
      recorded during the exercise stress test and scintigraphic tests (SPECT) in
      patients with ischemic heart disease was examined. MATERIAL AND METHODS: The
      study group consisted of 33 patients after myocardial infarction. In the group of
      patients after myocardial infarction and with low left ventricular ejection
      fraction correlations of 70% between the test results of T-wave alternans and
      SPECT and 60% between the test results of T-wave alternans and stress test were
      found. RESULTS: In the group of patients after myocardial infarction but with
      high left ventricular ejection fraction correlations were respectively 39% and
      48%. The analysis of the electrocardiographic maps showed a strong dependence of
      this correlation on the T-wave alternans amplitude and location of the ECG
      measuring electrode on the chest. The results might suggest that in patients
      after myocardial infarction and at increased risk for sudden cardiac death T-wave
      alternans may also provide information about cardiac electrical instability
      associated with ischemia. CONCLUSIONS: It can also be assumed that the position
      of the electrode where the highest level of the T-wave alternans was detected can
      indicate the location of the ischemic region of the heart.

PMID- 25861296
TI  - Searching for factors associated with resistance to acetylsalicylic acid used for
      secondary prevention of stroke.
AB  - INTRODUCTION: The aim of the study was to evaluate the prevalence of resistance
      to acetylsalicylic acid (ASA), used for secondary prevention of stroke, including
      the assessment of risk factors associated with the lack of ASA anti-aggregatory
      action. MATERIAL AND METHODS: Patients after a transient ischaemic attack (TIA)
      or ischaemic stroke in the acute (n = 111) and chronic phase (n = 87) were
      enrolled in the study. The assessment of platelet function was performed by whole
      blood impedance aggregometry using a multi-channel platelet function analyser
      (Multiplate). RESULTS: A proper response to ASA was found in 121 patients (61.1%)
      (ASA responders), a partial response to ASA in 59 patients (29.8%) (ASA partial
      responders), and ASA resistance in 18 patients (9.1%) (ASA non-responders).
      Acetylsalicylic acid resistance was observed more frequently in the chronic
      phase. The mean low-density lipoprotein (LDL) concentration was higher in ASA non
      responders (p = 0.02). The mean heart rate (p = 0.03) and the mean haematocrit (p
      = 0.03) were higher in the group of ASA partial responders and ASA non
      responders. Angiotensin II receptor antagonists were more often used in the group
      of ASA partial responders and ASA non-responders (p = 0.04). Diuretics were more
      rarely used by ASA non-responders, whereas fibrates were more rarely used by ASA
      partial responders. CONCLUSIONS: The method enabled the detection of ASA
      resistance in some patients with cerebrovascular disease. The study revealed some
      possible risk factors of ASA resistance: long ASA therapy, increased heart rate,
      higher LDL concentration, and higher haematocrit value. The relationship between
      the effect of ASA and other medications (angiotensin II receptor blockers,
      fibrates, diuretics) requires further study. Platelet function monitoring should
      be considered in patients at a greater risk of ASA resistance.

PMID- 25861297
TI  - The influence of statin therapy on platelet activity markers in hyperlipidemic
      patients after ischemic stroke.
AB  - INTRODUCTION: Low-density lipoprotein cholesterol (LDL-C) has been reported to
      increase platelet activation. Reducing the level of LDL-C with statins induces
      important pleiotropic effects such as platelet inhibition. This association
      between platelet activity and statin therapy may be clinically important in
      reducing the risk of ischemic stroke. We investigated the effect of simvastatin
      therapy on platelet activation markers (platelet CD62P, sP-selectin, and platelet
      derived microparticles (PDMPs)) in hyperlipidemic patients after ischemic stroke.
      MATERIAL AND METHODS: The study group consisted of 21 hyperlipidemic patients
      after ischemic stroke confirmed by CT, and 20 healthy subjects served as
      controls. We assessed the CD62P expression on resting and thrombin-activated
      blood platelets. CD62P and PDMPs were analyzed by the use of monoclonal
      antibodies anti-CD61 and anti-CD62 on a flow cytometer. The level of sP-selectin
      in serum was measured by the ELISA (enzyme-linked immunosorbent assay) method.
      All markers were re-analyzed after 6 months of treatment with simvastatin (20
      mg/day). RESULTS: Hyperlipidemic patients presented a significantly higher
      percentage of CD62+ platelets and higher reactivity to thrombin compared to
      control subjects. After simvastatin therapy hyperlipidemic patients showed a
      reduction of the percentage of resting CD62P(+) platelets (p = 0.005) and a
      reduction of expression and percentage of CD62P(+) platelets after activation by
      thrombin (median p < 0.05; percentage: p = 0.001). A decrease of sP-selectin
      levels (p = 0.001) and percentage of PDMPs (p < 0.05) in this group was also
      observed. CONCLUSIONS: HMG-CoA reductase inhibitor therapy in stroke patients
      with hyperlipidemia may be useful not only due to the lipid-lowering effect but
      also because of a significant role in reduction of platelet activation and
      reactivity.

PMID- 25861298
TI  - Peripheral vascular stiffness, assessed with two-dimensional speckle tracking
      versus the degree of coronary artery calcification, evaluated by tomographic
      coronary artery calcification index.
AB  - INTRODUCTION: Even in asymptomatic patients, the result of atherosclerosis
      progression is deterioration of the function and morphology of the artery wall.
      Two-dimensional speckle-tracking (2DST) is a sonographic technique that allows
      for precise evaluation of arterial wall compliance. Together with measurement of
      intima-media thickness (IMT), it can be applied for quick and non-invasive
      assessment of the progression of peripheral artery atherosclerosis. MATERIAL AND
      METHODS: Fifty-eight patients of mean age 61 years (SD 10.6) underwent cardiac
      computed tomography (CT) and subsequent ultrasonographic evaluation of the left
      common carotid artery. The calcium score was calculated according to the Agatston
      method and compared with IMT, circumferential strain variables assessed by 2DST,
      conventional arterial stiffness parameters (beta-stiffness index and elastic
      modulus) and clinical data. Intra-observer and inter-observer agreement was
      evaluated. RESULTS: Strain variables and IMT differed significantly in patients
      with calcium score (CS) > 0 and CS = 0. Moreover, they correlated with CS,
      systolic blood pressure and age of patients. Conventional stiffness parameters
      were not able to identify the group of patients with calcifications present in
      the coronary arteries. For the 2DST technique, interclass and intraclass
      agreements were 84.83% and 94.42% respectively. CONCLUSIONS: Circumferential
      strain variables assessed by 2DST and measurement of IMT can be used for
      evaluation of peripheral artery deterioration in patients until the 6(th) decade
      of life. These parameters reflect the development of calcifications in coronary
      arteries and, more importantly, can be used for a more detailed estimation of the
      atherosclerosis risk in patients with CS = 0.

PMID- 25861299
TI  - Tangent function transformation of the Abbreviated Injury Scale improves accuracy
      and simplifies scoring.
AB  - INTRODUCTION: The Injury Severity Score (ISS) and the New Injury Severity Score
      (NISS) are widely used for anatomic severity assessments after trauma. We present
      here the Tangent Injury Severity Score (TISS), which transforms the Abbreviated
      Injury Scale (AIS) as a predictor of mortality. MATERIAL AND METHODS: The TISS is
      defined as the sum of the tangent function of AIS/6 to the power 3.04 multiplied
      by 18.67 of a patient's three most severe AIS injuries regardless of body
      regions. TISS values were calculated for every patient in two large independent
      data sets: 3,908 and 4,171 patients treated during a 6-year period at level-3
      first-class comprehensive hospitals: the Affiliated Hospital of Hangzhou Normal
      University and Fengtian Hospital Affiliated to Shenyang Medical College, China.
      The power of TISS to predict mortality was compared with previously calculated
      NISS values for the same patients in each data set. RESULTS: The TISS is more
      predictive of survival than NISS (Hangzhou: receiver operating characteristic
      (ROC): NISS = 0.929, TISS = 0.949; p = 0.002; Shenyang: ROC: NISS = 0.924, TISS =
      0.942; p = 0.008). Moreover, TISS provides a better fit throughout its entire
      range of prediction (Hosmer Lemeshow statistic for Hangzhou NISS = 29.71; p <
      0.001, TISS = 19.59; p = 0.003; Hosmer Lemeshow statistic for Shenyang NISS =
      33.49; p < 0.001, TISS = 21.19; p = 0.002). CONCLUSIONS: The TISS shows more
      accurate prediction of prognosis and a linear relation to mortality. The TISS
      might be a better injury scoring tool with simple computation.

PMID- 25861300
TI  - One-step nucleic acid amplification testing in medullary thyroid cancer lymph
      nodes: a case series.
AB  - INTRODUCTION: Locoregional relapse in medullary thyroid cancer (MTC) may be
      caused by nodal micrometastases. Medullary thyroid cancer lymph nodes have not
      yet been evaluated by one-step nucleic acid amplification (OSNA). Therefore, the
      aim of this study was to detect MTC cells by OSNA in cervical lymph nodes and
      compare the obtained outcomes with conventional histopathology. MATERIAL AND
      METHODS: Twenty-one randomized, unenlarged lymph nodes from 5 patients with MTC
      were examined by histopathology and OSNA. Lymph nodes were divided into four
      representative blocks by a sterile, single use, special cutting device in the
      same way as in the clinical protocol study performed by Tsujimoto et al. Two
      blocks were used for histopathology and immunohistochemistry, 2 for OSNA.
      RESULTS: Positive results of histopathology and OSNA were revealed in 4 patients.
      The outcomes of OSNA and histopathology were corresponding in 3 patients.
      Positive histopathology results of 2 lymph nodes from 2 patients were confirmed
      by OSNA. In 1 patient there were only negative results of both examinations. One
      step nucleic acid amplification failed to detect metastasis in 1 lymph node in 2
      patients although it did not change the TNM status in these patients. There were
      no false positive results in the OSNA test. CONCLUSIONS: One-step nucleic acid
      amplification may be an alternative method to histopathology in detecting nodal
      involvement in MTC. Further studies should evaluate the sensitivity and
      specificity of OSNA and the impact on staging in MTC.

PMID- 25861301
TI  - Cerebroplacental ratio in prediction of adverse perinatal outcome and fetal heart
      rate disturbances in uncomplicated pregnancy at 40 weeks and beyond.
AB  - INTRODUCTION: The aim of the study was to determine the usefulness of Doppler
      velocimetry, based on cerebroplacental ratio (C/U) evaluation, in predicting
      intrapartum fetal heart rate abnormalities and adverse neonatal outcome in
      uncomplicated pregnancies at 40 weeks and beyond. MATERIAL AND METHODS: One
      hundred and forty-eight women in uncomplicated pregnancies, between 40 and 42
      completed weeks, were divided into control and study groups: with the absence (n
      = 79) and with the presence of a fetal brain-sparing effect (n = 69),
      respectively. Pulsatility and resistance indices in the middle cerebral, the
      umbilical artery and the C/U ratio were evaluated daily by Doppler
      ultrasonography. C/U < 1.1 was reported as suggestive of a brain-sparing effect.
      Abnormal flow indices were analyzed and compared to adverse pregnancy and
      neonatal outcome determinants. RESULTS: In the abnormal C/U group the abnormal
      CTG records were significantly more frequently observed (62.3%) than in normal
      C/U group (19.0%) (p = 0.0001). The comparison of selected Doppler indices
      revealed that C/U showed the highest sensitivity in prediction of both the
      intrapartum abnormal FHR (74.1%) and the adverse neonatal outcome (87.8%).
      CONCLUSIONS: The C/U index shows the highest sensitivity in prediction of FHR
      abnormalities and adverse neonatal outcome in uncomplicated pregnancies at 40
      weeks and beyond. The C/U index is useful in clinical practice in antenatal
      monitoring of these women in order to select those at high risk of intra- and
      postpartum complications.

PMID- 25861302
TI  - Association of functional genetic variants of A-kinase anchoring protein 10 with
      QT interval length in full-term Polish newborns.
AB  - INTRODUCTION: A-Kinase Anchoring Proteins (AKAPs) coordinate the specificity of
      protein kinase A signaling by localizing the kinase to subcellular sites. The
      1936G (V646) AKAP10 allele has been associated in adults with low
      cholinergic/vagus nerve sensitivity, shortened PR intervals in ECG recording and
      in newborns with increased blood pressure and higher cholesterol cord blood
      concentration. The aim of the study was to answer the question of whether 1936A >
      G AKAP10 polymorphism is associated with the newborn electrocardiographic
      variables. MATERIAL AND METHODS: Electrocardiograms were recorded from 114
      consecutive healthy Polish newborns (55 females, 59 males), born after 37
      gestational weeks to healthy women with uncomplicated pregnancies. All recordings
      were made between 3(rd) and 7(th) day of life to avoid QT variability. The heart
      rate per minute and duration of PR, QRS, RR and QT intervals were usually
      measured. The ECGs were evaluated independently by three observers. At birth,
      cord blood of neonates was obtained for isolation of genomic DNA. RESULTS: The
      distribution of anthropometric and electrocardiographic variables in our cohort
      approached normality (skewness < 2 for all variables). No significant differences
      in anthropometric variables and electrocardiographic traits with respect to
      AKAP10 genotype were found. Multiple regression analysis with adjustment for
      gender, gestational age and birth mass revealed that QTc interval in GG AKAP10
      homozygotes was significantly longer, but in range, when compared with A alleles
      carriers (AA + AG, recessive mode of inheritance). No rhythm disturbances were
      observed. CONCLUSIONS: Results demonstrate possible association between AKAP10
      1936A > G variant and QTc interval in Polish newborns.

PMID- 25861303
TI  - A cross-sectional study of growth, nutritional status and body proportions in
      children and adolescents at a medical center specializing in the treatment of
      cystic fibrosis in Poland.
AB  - INTRODUCTION: Malnutrition, delayed growth and delayed puberty are commonly seen
      in children with cystic fibrosis. The aim of this study was to evaluate growth,
      nutritional status and body proportions in children and adolescents suffering
      from cystic fibrosis. MATERIAL AND METHODS: The evaluation was based on 19
      somatic measurements and indices calculated from these measurements. Somatic
      development was evaluated in relation to several factors connected to the
      clinical picture or the course of the disease. Anthropometric data were extracted
      from the medical histories of 41 boys and 48 girls diagnosed and treated at the
      Institute of Mother and Child in Warsaw (Poland). Mean values for somatic
      parameters and body build indices for the children suffering from CF were
      compared to those for the reference group. RESULTS: The results revealed that
      growth in these children was significantly delayed in comparison to that seen in
      the healthy population (Z-score = -0.56, p < 0.001). Nutritional status was also
      adversely affected (Z-score = -0.85, p < 0.001). The children suffered more from
      a deficit in muscularity than in adiposity (Z-score = -0.75 and Z-score = -0.34,
      p < 0.01, respectively). This was especially true for boys. The children had
      infantile body proportions and defects in trunk and chest structure. CONCLUSIONS:
      The factors that most affected somatic development were infection by Pseudomonas
      aeruginosa and the time at which the disease was diagnosed. Chronic infection by
      P. aeruginosa and type of CFTR mutation were the factors that most affected
      pulmonary function parameters.

PMID- 25861304
TI  - Efficacy of gefitinib or erlotinib in patients with squamous cell lung cancer.
AB  - INTRODUCTION: The aim of this study was to evaluate the feasibility of epidermal
      growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) and EGFR mutation
      frequency in advanced squamous cell lung cancer based on the data from our
      hospital. MATERIAL AND METHODS: The clinical data of 102 patients with advanced
      squamous cell lung cancer who were admitted to Zhejiang Cancer Hospital from
      January 2007 to December 2011 were retrospectively analyzed. Survival analysis
      was evaluated by the Kaplan-Meier method. The EGFR mutations were assessed in
      some of the patients using the pyrosequencing assay. RESULTS: Nine patients
      (8.8%) showed a partial response (PR), 28 (27.5%) achieved stable disease (SD),
      and 65 (63.7%) had progressive disease (PD). The disease control rate was 36.3%
      and the median progression-free survival (PFS) was 1.93 months (95% CI: 1.57
      2.29). The PFS in patients who obtained disease control in the prior TKI was 8.63
      months and 1.37 months in the disease progression cases (p < 0.001). No
      statistical differences in PFS were observed between gefitinib and erlotinib (2.0
      months vs. 1.87 months, p = 0.76). The toxicities associated with EGFR-TKI were
      generally acceptable. In 74 patients with adequate specimens for molecular
      analysis, 4 (5.4%) had EGFR mutations (2 with deletions within exon 19 and 2 with
      L858R mutation in exon 21). CONCLUSIONS: The EGFR-tyrosine kinase inhibitor seems
      to be a potential therapeutic option for treatment of advanced squamous cell lung
      cancer patients. Erlotinib and gefitinib had a similar efficacy in advanced
      squamous cell lung cancer. The frequency of EGFR mutation was about 5.4% in our
      single hospital data.

PMID- 25861305
TI  - Restricting sports activity in reducing the rate of varicocele and related
      infertility parameters in athletes.
AB  - INTRODUCTION: The aim of this study is to test the hypothesis that the cessation
      of sports training in young athletes reduces the prevalence of varicocele.
      MATERIAL AND METHODS: 1,013 young males were divided into three age-matched
      groups based on their sport activity. The first group consisted of 305
      athletically active boys in basketball, volleyball, handball, or football; the
      second of 44 active water-polo players, and the third of 664 sport-inactive
      controls. All participants had been initially examined for the presence of
      varicocele, and positive ones were submitted to orchidometry and seminal fluid
      analysis. Those with varicocele were then asked to cease all sport activity for
      the following six months, and the reassessing was performed. RESULTS: The results
      showed a significantly higher percentage of varicocele present in the first group
      than in the control group (p < 0.49), while the percentage of young males
      diagnosed with varicocele in the second proved to be even lower than that of the
      control group (9.09% vs. 12.35%). After the 6-month period of cessation and
      abstention from all sporting activity, every parameter of the seminal fluid
      analysis improved in the first group, wherein statistical significance for both
      sperm concentration (p < 0.001) and sperm motility (p < 0.023) was found. The
      testicular volume was found not to have increased significantly in either group
      (p > 0.05). CONCLUSIONS: The study shows that sport-associated varicocele has a
      positive prognosis when diagnosed early and upon the cessation of sports
      training.

PMID- 25861306
TI  - Cross-sectional study of C1-S5 vertebral bodies in human fetuses.
AB  - INTRODUCTION: Knowledge on the normative spinal growth is relevant in the
      prenatal detection of its abnormalities. The present study determines the height,
      transverse and sagittal diameters, cross sectional area, and volume of individual
      C1-S5 vertebral bodies. MATERIAL AND METHODS: Using the methods of computed
      tomography (CT), digital image analysis, and statistics, the size of C1-S5
      vertebral bodies in 55 spontaneously aborted human fetuses aged 17-30 weeks was
      examined. RESULTS: All the 5 examined parameters changed significantly with
      gestational age (p < 0.01). The mean height of vertebral bodies revealed an
      increase from the atlas (2.39 +/-0.54 mm) to L2 (4.62 +/-0.97 mm), stabilized
      through L3-L4 (4.58 +/-0.92 mm, 4.61 +/-0.84 mm), and then was decreasing to S5
      (0.43 +/-1.06 mm). The mean transverse diameter of vertebral bodies was
      increasing from the atlas (1.20 +/-1.96 mm) to L1 (6.24 +/-1.46 mm), so as to
      stabilize through L2-L3 (6.12 +/-1.65, 6.12 +/-1.61 mm), and finally was
      decreasing to S5 (0.26 +/-0.96 mm). There was an increase in sagittal diameter of
      vertebral bodies from the atlas (0.82 +/-1.34 mm) to T7 (4.76 +/-0.85 mm), its
      stabilization for T8-L4 (4.73 +/-0.86 mm, 4.71 +/-1.02 mm), and then a decrease
      in values to S5 (0.21 +/-0.75 mm) was observed. The values for cross-sectional
      area of vertebral bodies were increasing from the atlas (2.95 +/-5.25 mm(2)) to
      L3 (24.92 +/-11.07 mm(2)), and then started decreasing to S5 (0.48 +/-2.09
      mm(2)). The volumetric growth of vertebral bodies was increasing from the atlas
      (8.60 +/-16.40 mm(3)) to L3 (122.16 +/-74.73 mm(3)), and then was decreasing to
      S5 (1.60 +/-7.00 mm(3)). CONCLUSIONS: There is a sharp increase in size of fetal
      vertebral bodies between the atlas and the axis, and a sharp decrease in size
      within the sacral spine. In human fetuses the vertebral body growth is
      characterized by maximum values in sagittal diameter for T7, in transverse
      diameter for L1, in height for L2, and in both cross-sectional area and volume
      for L3.

PMID- 25861307
TI  - Mechanism of endothelial cyto-protective and thrombo-resistance effects of
      sildenafil, vardenafil and tadalafil in male rabbit.
AB  - INTRODUCTION: PDE5 inhibitors (PDE5inhs) have proven to be of great impact in the
      treatment of numerous human extra-sexual diseases and their chronic use may
      induce endothelial rehabilitation. This study aimed to assess the effects of
      PDE5inhs at chronic administration to explore the possible endothelial cyto
      protective and thrombo-resistance effects. MATERIAL AND METHODS: One hundred New
      Zealand white male rabbits were divided into four groups. The first group
      (control, C) received 1 ml saline/kg, the second group (S) received 10 mg/kg
      sildenafil, the third group (V) received 2 mg/kg vardenafil, and the fourth group
      (T) received 2 mg/kg tadalafil in saline I.P. three times weekly for 4 weeks.
      Blood samples were collected and plasma was isolated for determination of 2,3
      dinor-6-keto-prostaglandin F-1alpha (PGF1alpha), 11-dehydro-TXB2 (TXB2),
      fibrinogen, calcium levels, prothrombin (PT), and thrombin times (TT). RESULTS:
      PDE5inhs significantly increase PGF1alpha, calcium levels, PT and TT (p < 0.001)
      when compared with baseline data or with the saline group at the end of
      treatment. In contrast, PDE5inhs significantly decrease TXB2 and fibrinogen
      levels (p < 0.001) when compared either with their baseline data or with the
      saline group at the end of treatment. The tadalafil group showed a lower increase
      in PGF1alpha (p < 0.001), lower decrease in TXB2 (p < 0.001), and higher increase
      in calcium levels (p < 0.01, p < 0.05), lower increase in PT and TT levels (p <
      0.001) when compared with sildenafil or vardenafil. CONCLUSIONS: The prolonged
      use of PDE5inhs has time-dependent mild to moderate endothelial cyto-protective,
      thrombo-resistance anti-inflammatory and anti-nociception effects via activation
      of endothelial NOS (eNOS), increase of PGI2 synthesis and decrease of fibrinogen
      with significant increase in PT and TT.

PMID- 25861308
TI  - Concomitant protective and therapeutic role of verapamil in chronic mercury
      induced nephrotoxicity in the adult rat: histological, morphometric and
      ultrastructural study.
AB  - INTRODUCTION: Mercury intoxication is a widespread problem as mercury is used in
      the manufacture of thermometers, batteries and electrical switches. It forms one
      of the most diffusible environmental pollutants. Mercury has a nephrotoxic effect
      which could occur at low exposure levels. Verapamil could help in the treatment
      of mercuric toxicity. The aim of the study was to examine the protective and
      therapeutic effect of concomitant verapamil on chronic mercuric chloride
      nephrotoxicity. This was done through histological, morphometric and transmission
      electron microscopic studies. MATERIAL AND METHODS: Sixty adult male albino rats
      were used. The rats were divided into a control group and 4 experimental groups:
      group I (HgCl2), group II (concomitant HgCl2 and verapamil), group III (HgCl2
      withdrawal) and group IV (HgCl2 withdrawal then verapamil treatment). RESULTS:
      Chronic administration of HgCl2 resulted in cortical nephrotoxic effects in the
      form of glomerular sclerosis, acute tubular necrosis and interstitial
      inflammatory cellular infiltration which eventually ended in interstitial
      fibrosis. Concomitant use of verapamil with HgCl2 improved the previous
      pathological changes partially. The findings in group III were less severe
      compared to group IV. The persistence of the pathological findings in these
      groups reflects the irreversible nephrotoxic changes caused by chronic HgCl2
      exposure. CONCLUSIONS: We concluded that the concomitant administration of
      verapamil has a much better effect in minimizing the nephrotoxic effect caused by
      chronic HgCl2 than its therapeutic administration. So, we recommended the
      prophylactic use of verapamil in suspected cases of chronic mercuric chloride
      nephrotoxicity to preserve renal function.

PMID- 25861309
TI  - In vivo evaluation of nerve guidance channels of PTMC/PLLA porous biomaterial.
AB  - INTRODUCTION: Peripheral nerve disruptions, frequently occurring during limb
      injuries, give rise to serious complications of patients recovery resulting from
      limitations in neural tissue regeneration capabilities. To overcome this problem
      bridging techniques utilizing guidance channels gain their importance.
      Biodegradable polymeric tubes seem to be more prospective then non-degradable
      materials - no necessity of implant removal and possibilities of release of
      incorporated drugs or biologically active agents that may support nerve
      regeneration process are the main advantages. MATERIAL AND METHODS: Polymer blend
      of commercial poly(L-lactic acid) (PLLA) and in-house synthesized
      poly(trimethylene carbonate) (PTMC) were processed in an organic solvent - phase
      inversion process on a supporting rod - to form a guidance porous tube of 1.1 mm
      inner diameter. In vivo experiments on rat's cut femoral nerve by using either
      the tubes or end-to-end suturing (control group) involved 22 and 19 rats,
      respectively. Motor recovery of operated limbs, neuroma occurrence and
      histopathology of explanted nerves were evaluated after 30, 60 and 90 days of
      implantation. RESULTS: Motor recovery of the limbs was of similar rate for the
      two animal groups. The neuroma formation was evident in over 90% control
      specimens, while for the bridging group it was less than 40% of all evaluable
      samples (p = 0.0022). Biocompatibility of applied materials was affirmed by
      moderate tissue response. CONCLUSIONS: Application of the biodegradable PLLA/PTMC
      polymeric tubes effectively supports regeneration of discontinued nerves. The
      applied material prevents neuroma formation, by reducing the scar tissue
      formation time and, thus, accelerating the process of neural tissue restoration.

PMID- 25861311
TI  - Dysfunctional high-density lipoprotein: not only quantity but first of all
      quality?

PMID- 25861310
TI  - Evaluation of the protective effect of Nigella sativa extract and its primary
      active component thymoquinone against DMBA-induced breast cancer in female rats.
AB  - INTRODUCTION: The historical use of black cumin seed (Nigella sativa) dates back
      centuries, being embedded in Arabian culture and having a long history of
      unsurpassed medicinal value with versatility to treat a wide range of ailments.
      Thymoquinone (TQ) is now known to be the primary active constituent of black
      cumin seed oil (BCS oil) responsible for its medicinal effects and also showing
      promise for treatment of cancer. MATERIAL AND METHODS: In the current study, we
      have studied the effects of TQ and BCS oil on tumor markers (MDA, LDH, ALP and
      AST), histopathological alterations and the regulation of several genes (Brca1,
      Brca2, Id-1 and P53 mutation) related to breast cancer in female rats induced by
      7,12-dimethylbenz[a]anthracene (DMBA) treatment. Rats received a single dose (65
      mg/kg b.w.) of DMBA via an intragastric tube to induce breast cancer. Animals
      that received DMBA were treated orally with 1, 5, 10 mg/kg of TQ or BCS oil via
      an intragastric tube three times per week for 4 months. RESULTS: We found that TQ
      and then BCS reduced the rate of tumor markers (levels of MDA and LDH as well as
      ALP and AST activities), inhibited the histopathological alterations and
      decreased the expression of the Brca1, Brca2, Id-1 and P53 mutations in mammary
      tissues of female rats induced by DMBA treatment. CONCLUSIONS: The results
      suggest that TQ and BCS oil exert a protective effect against breast carcinogens.
      The antioxidant property of TQ and BCS oil is mediated by their actions and
      investigating other underlying mechanisms merits further studies.

PMID- 25861312
TI  - Multiple keloids in a 16-year-old boy with Rubinstein-Taybi syndrome.

PMID- 25861313
TI  - Possible association between fluconazole administration and acute hyperkalemia in
      a critically ill cyanotic infant.

PMID- 25861314
TI  - Successful pregnancy after conservative management of early stage endometrial
      carcinoma in a young nulliparous woman.

PMID- 25861315
TI  - Vulvar melanoma with urethral invasion and bladder metastases - a case report and
      review of the literature.

PMID- 25861316
TI  - Optimization of Three Dimensional Culturing of the HepG2 Cell Line in Fibrin
      Scaffold.
AB  - BACKGROUND: A potential treatment for healing hepatic tissue is delivering
      isolated hepatic cells to the site of injury to promote hepatic cells formation.
      In this technology, providing an appropriate injectable system for delivery of
      hepatic cells is an important issue. In this regard, fibrin scaffolds were
      designed with many advantages over other scaffolds like cell delivery vehicles
      for biodegradation, biocompatibility and hemostasis. OBJECTIVES: The aim of this
      study was to determine suitable cell culture circumstances for HepG2 cell
      proliferation and differentiation in 3D fibrin scaffolds by evaluating Ca(2+)
      concentrations, cell numbers, various ratios of plasma/RPMI 1640 and thickness of
      fibrin scaffold. MATERIALS AND METHODS: In a one-stage experimental design, Box
      Behnken design strategy was performed by Minitab 15 software (version 15,
      Minitab. State College, PA) with three factors at three levels (low, medium and
      high) and 27 runs for identification of the effects of ratio of plasma/RPMI 1640,
      Ca(2+) concentration and thickness on the formation of fibrin gel scaffold and 3D
      HepG2 culture. RESULTS: The optimal concentrations for fibrin scaffold
      fabrication were achieved by adding 0.15 mol CaCl2 (50 uL) and 1 * 10(5) cells to
      1:4 of plasma/RPMI 1640 ratio (500 uL with 2.3 mm thickness per well).
      CONCLUSIONS: Our approach provided easy handle method using inexpensive materials
      like human plasma instead of purified fibrinogen to fabricate fibrin scaffold.

PMID- 25861317
TI  - Targeting Human Telomerase Reverse Transcriptase by a Simple siRNA Expression
      Cassette in HepG2 Cells.
AB  - BACKGROUND: Human telomerase reverse transcriptase (hTERT) has become an ideal
      target for development of anticancer therapy. Small interfering RNAs (siRNAs) are
      very powerful reagents for gene silencing and show promise for cancer gene
      therapy. However, only a small number of siRNAs have been demonstrated to be
      effective. For gene therapy targeting hTERT, it is essential to develop a robust
      system to fully explore the power of siRNAs. OBJECTIVES: We explored a siRNA
      expression cassette (SEC) to screen highly effective RNAi-targeted sequences for
      gene therapy of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: An SEC was
      developed by flanking H1 and U6 promoters in opposite directions at the siRNA
      encoding sequence. Eight SECs specific to hTERT were designed by overlap
      extension polymerase chain reaction (PCR) and transfected into HepG2 cells with
      calcium phosphate. The telomerase activity was determined by telomeric repeat
      amplification protocol (TRAP) silver staining and TRAP real-time PCR analysis.
      The mRNA and protein expression levels of hTERT were determined by reverse
      transcription (RT)-PCR and western blot, respectively. Cell viability was
      determined by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide
      (MTT) assay and cell apoptosis was measured by the annexin-V/propidium iodide
      (PI) assay coupled with flow cytometry. RESULTS: Eight hTERT-specific SECs (SEC-1
      8) were successfully constructed. In comparison to that of the negative control
      SEC, the hTERT-specific SECs, especially, SEC-4, SEC-5, SEC-7 and SEC-8
      significantly reduced the activity of hTERT in HepG2 cells at 48 hours after
      transfection. Moreover, the mRNA and protein expression levels of hTERT as well
      as the cell viability were significantly reduced by SECs. Knockdown of hTERT by
      SECs in HepG2 cells led to cell apoptosis. CONCLUSIONS: Our developed simple SEC
      was a powerful strategy for screening highly effective RNAi-targeted sequences
      and showed promise for gene therapy of HCC.

PMID- 25861318
TI  - Pegylated Interferon alpha Therapy in Chronic Delta Hepatitis: A One-Center
      Experience.
AB  - BACKGROUND: The only established therapy for chronic viral delta hepatitis, the
      most severe form of viral hepatitis is treatment with pegylated-interferon alpha
      (Peg IFN alpha). OBJECTIVES: In this study, we aimed to determine the efficacy of
      pegylated-interferon alpha 2a (Peg-IFN alpha 2a) and 2b (Peg IFN alpha 2b) in the
      treatment of patients infected with chronic delta hepatitis virus. PATIENTS AND
      METHODS: The sample size was based on available patients potentially to be
      recruited. Data of 63 patients receiving either Peg IFN alpha 2a or Peg IFN alpha
      2b were retrospectively assessed in the present cohort study performed in Turkey.
      Of 56 patients completed the study, 41 received Peg IFN alpha 2a and 15 received
      Peg IFN alpha 2b for 12 months. Patients were evaluated for biochemical and
      virological responses at the end of given treatment and six months after the
      treatment. RESULTS: Stage of fibrosis was found high in both groups (85.4% vs.
      86.7%), while cirrhosis was higher in the group of Peg IFN alpha 2b (53.3% vs.
      34.1%). At the end of treatment, either hepatitis delta virus RNA (HDV RNA) alone
      or both HDV RNA and hepatitis b virus DNA (HBV DNA) had negative results in 32%
      of patients. Although HDV RNA negativity was sustained in 30.3% of patients,
      negativity of both HDV RNA and HBV DNA was decreased to 19.6% six months after
      completion of the treatment. HBV DNA became positive in one third of patients
      with response at six months after completion of the treatment (10.7% of all
      patients). HDV RNA negativity at month six was found as a predictor of positive
      response. No significant difference was found between Peg IFN alpha 2a and Peg
      IFN alpha 2b for virological response rate. CONCLUSIONS: Treatment with Peg IFN
      alpha achieved a sustained negativity of HDV RNA in about one third of patients.
      Duration of Peg IFN alpha therapy might be prolonged to at least 24 months or
      more to prevent the occurrence of Hepatitis B virus (HBV) relapse encountered six
      months after completion of the treatment.

PMID- 25861319
TI  - Evaluation of the effect of cardiac rehabilitation on left ventricular diastolic
      and systolic function and cardiac chamber size in patients undergoing
      percutaneous coronary intervention.
AB  - BACKGROUND: Exercise and rehabilitation are important methods for decreasing the
      risk factors of coronary artery disease (CAD). We aimed to evaluate the effect of
      the cardiac rehabilitation (CR) exercise program on the cardiac structure and
      physiology in patients undergoing percutaneous coronary intervention (PCI).
      METHODS: In this randomized controlled study, 146 patients with CAD were divided
      equally into two groups: case group (undertaking CR after PCI) and control group
      (without rehabilitation after PCI). All the patients in the case group underwent
      echocardiography (before and after CR), and echocardiography was performed for
      the control group simultaneously. The CR exercise program encompassed 24
      sessions, twice or three times a week, with each session lasting between 15 and
      45 minutes, depending on the individual patient's tolerance. Left ventricular
      (LV) ejection fraction, LV diastolic function, LV end-systolic and diastolic
      diameter, and right ventricular (RV) end-diastolic diameter were measured in the
      CR group before and after rehabilitation and compared to those in the control
      group at the same times. RESULTS: In this study, 146 patients (46 female and 100
      male) were evaluated: 73 in the rehabilitation group and 73 in the control group.
      The mean age of the patients in the CR and control groups was 58.05 +/- 10.27 and
      56.76 +/- 10.07 years, respectively. The CR exercise program had useful effects
      on LV diastolic function after PCI. The distribution of LV diastolic dysfunction
      after the CR exercise program was changed significantly only in the CR group (p
      value = 0.043). In the CR group, normal, grade I, grade II, and grade III LV
      diastolic dysfunction were observed in 20.5%, 69.8%, 6.8%, and 2.7%,
      respectively. This distribution was changed respectively to 30.1%, 61.6%, 5.4%,
      and 2.7% following CR, which showed a significant improvement due to CR in LV
      diastolic function, most prominently in the patients with grade I diastolic
      dysfunction (p value = 0.390). There was no significant change in LV and RV
      diameter before and after rehabilitation, while the ejection fraction increased
      significantly (p value < 0.05) in both groups. CONCLUSION: The RC exercise
      program can be effective in the augmentation of LV diastolic dysfunction after
      PCI, without significant changes in LV diameters.

PMID- 25861320
TI  - Incidence and etiology of chylothorax after congenital heart surgery in children.
AB  - BACKGROUND: Chylothorax is a rare but serious postoperative condition with a high
      rate of morbidity and may lead to the mortality of children undergoing congenital
      heart disease (CHD) surgery. This study evaluated the specific surgical
      procedures associated with the higher risk of postoperative chylothorax. METHODS:
      We assessed 435 cases undergoing CHD surgery between April 2003 and May 2006. We
      detected postoperative chylothorax in 6 patients. The diagnosis of chylothorax
      was established based on the presence of an odorless fluid with the
      characteristic milky appearance of the fluid (except when the patients were
      fasting in the immediate postoperative period), a triglyceride level greater than
      110 mg/dL or between 50 and 110 mg/dL with a pleural fluid white cell count
      greater than 1000, and more than 80% lymphocytes on differential when the pleural
      fluid was not chylous. RESULTS: Over a 37-month period, 435 (mean age = 51.6
      months; 232 males) patients underwent various types of surgical procedures for
      CHD; 6 patients developed chylothorax after the Fontan operation; one patient
      died due to severe chylothorax; 3 patients were managed by nutritional
      modifications, diuretics, and thoracocentesis; and 2 patients required thoracic
      duct ligation. The Fisher exact test analysis showed a significant association
      between the Fontan operation and postoperative chylothorax (p value < 0.0001).
      CONCLUSION: Our study showed a significant association between the Fontan surgery
      and chylothorax.

PMID- 25861321
TI  - Mean Platelet Volume as a Predictor of One-Year Major Adverse Cardiac Events
      following Elective Percutaneous Coronary Interventions.
AB  - BACKGROUND: Mean platelet volume (MPV) correlates with platelet activity. The
      relation between MPV and long-term outcome in patients undergoing percutaneous
      coronary intervention (PCI) has been investigated in several studies. The aim of
      the present study was to investigate the utility of MPV in prognosticating the
      long-term outcome after elective PCI. METHODS: The study cohort included 2627
      patients undergoing elective PCI between September 2008 and June 2010, whose
      baseline MPV measurements before PCI were available. The patients were divided
      into three groups of MPV < 9.1 fL, MPV = 9.1 to 10 fL, and MPV > 10 fL, and they
      were assessed for developing major adverse cardiac events (MACE), comprising
      death, myocardial infarction (MI), target vessel revascularization (TVR), and
      target lesion revascularization (TLR) over a one-year follow-up. RESULTS: Of 2539
      patients, major adverse cardiac events (MACE) at one year occurred in 77 (3.0%)
      patients, including mortality in 26 (1.0%). The patients in the highest tertile
      (MPV > 10 fL) had no increased frequency of MACE compared to those in the mid
      (9.1 to 10 fL) and lowest (< 9.1 fL) tertiles (3.3%, 2.2%, and 3.8%,
      respectively; p value = 0.14). No significant differences were found for each of
      the primary endpoints among the MPV tertiles. In multivariate logistic
      regression, we investigated the association between high MPV and total MACE (OR =
      1.10, 95%CI: 0.69-1.77; p value = 0.68), death (OR = 1.14, 95%CI: 0.51-2.54; p
      value = 0.74), and non-fatal MI (OR = 1.85, 95%CI: 0.73-4.67; p value = 0.19) at
      one year's follow-up but MPV did not remain in the model in any of the cases. In
      the diabetic patients, the one-way analysis of variance demonstrated that
      mortality was 1.6% (4 patients) in the highest tertile, 0.8% (2 patients) in the
      mid tertile, and 0.5% (one patient) in the lowest tertile. CONCLUSION: There was
      no direct correlation between pre-procedural MPV and MACE in elective PCI. MPV
      can only be considered as an appropriate factor for predicting mortality in
      diabetic patients undergoing elective PCI.

PMID- 25861322
TI  - Erectile dysfunction as a predictor of early stage of coronary artery disease.
AB  - BACKGROUND: Diagnosis of coronary artery disease (CAD) in early stages is vital
      in decreasing mortality by reducing the risk factors. The aim of this study was
      to investigate the association between erectile dysfunction (ED) and CAD.
      METHODS: A total of 200 patients were divided into four groups according to their
      angiography results: Group 1 (G1, n = 59): patients with one-vessel disease (1
      VD); Group 2 (G2, n = 40): patients with two-vessel disease (2-VD); Group 3 (G3,
      n = 50): patients with three-vessel disease (3-VD); and controls (C, n = 51)
      without any coronary disease. The International Index of Erectile Function (IIEF)
      was completed for all the patients to assess their sexual function and ED in the
      last 6 months. RESULTS: Mean age of the participants was 57.69 +/- 12.466 years.
      The prevalence of ED in the CAD patients was significantly higher than that of
      the controls (75.16% vs. 60.8%; p value = 0.041). There was a significant direct
      correlation between the number of involved vessels in the CAD patients and ED
      severity (r: 0.183; p value = 0.010), and the ED rate increased with age.
      CONCLUSION: In conclusion, ED severity correlated with the number of involved
      vessels documented by coronary angiography. Consequently, ED may be considered a
      possible marker for the development of atherosclerosis and CAD.

PMID- 25861323
TI  - Assessment of subclinical left ventricular dysfunction in patients with chronic
      mitral regurgitation using torsional parameters described by tissue Doppler
      imaging.
AB  - BACKGROUND: Left ventricular (LV) twist is due to oppositely directed apical and
      basal rotation and has been proposed as a sensitive marker of LV function. We
      sought to assess the impact of chronic pure mitral regurgitation (MR) on the
      torsional mechanics of the left human ventricle using tissue Doppler imaging.
      METHODS: Nineteen severe MR patients with a normal LV ejection fraction and 16
      non-MR controls underwent conventional echocardiography and apical and basal
      short-axis color Doppler myocardial imaging (CDMI). LV rotation at the apical and
      basal short-axis levels was calculated from the averaged tangential velocities of
      the septal and lateral regions, corrected for the LV radius over time. LV twist
      was defined as the difference in LV rotation between the two levels, and the LV
      twist and twisting/untwisting rate profiles were analyzed throughout the cardiac
      cycle. RESULTS: LV twist and LV torsion were significantly lower in the MR group
      than in the non-MR group (10.38 degrees  +/- 4.04 degrees  vs. 13.95 degrees  +/-
      4.27 degrees ; p value = 0.020; and 1.29 +/- 0.54  degrees /cm vs. 1.76 +/- 0.56 
      degrees /cm; p value = 0.021, respectively), both suggesting incipient LV
      dysfunction in the MR group. Similarly, the untwisting rate was lower in the MR
      group (-79.74 +/- 35.97  degrees /s vs.-110.96 +/- 34.65  degrees /s; p value =
      0.020), but there was statistically no significant difference in the LV twist
      rate. CONCLUSION: The evaluation of LV torsional parameters in MR patients with a
      normal LV ejection fraction suggests the potential role of these sensitive
      variables in assessing the early signs of ventricular dysfunction in asymptomatic
      patients.

PMID- 25861324
TI  - Percutaneous treatment for aneurysmal coarctation of the aorta with covered
      stenting: a case report.
AB  - The coarctation of the aorta (CoA) is rare in adulthood. Diagnosis is made by
      clinical suspicion and physical findings such as blood pressure difference
      between the upper and lower extremities, pulse delay in the femoral artery, and
      systolic murmur over the thoracic spine. The CoA in adulthood and in patients
      with associated aneurysm is challenging and different complications even with
      proper treatment can occur. Covered stents are indicated in concomitant aneurysm,
      older age, and tight coarctation. A 26-year-old male with resistant hypertension
      due to a CoA diagnosed by computed tomography angiography referred to our center
      for an attempted stent implantation. Cardiac catheterization and aortography
      revealed a long CoA after the origin of the left subclavian artery with a 60 mmHg
      gradient. Moreover, there was a large aneurysm in the site of the coarctation.
      Under general anesthesia and fluoroscopic guidance, two balloon-expandable
      covered Cheatham-Platinum stents (size 18 in 44 millimeters and size 18 in 50
      millimeters) were successfully implanted across the CoA with no residual
      gradient. On 2 years' follow-up, the patient had no symptoms except for mild
      hypertension. In this patient, the use of a covered stent within the aneurysm was
      safe and effective. 

PMID- 25861325
TI  - Anesthetic Management in Complex Arch Surgery: Debranching of Innominate and Left
      Common Carotid Arteries in Extensive Aortic Dissection without Cardiopulmonary
      Bypass.
AB  - Aortic dissection begins with the formation of a tear in the aortic intima, and
      it directly exposes an underlying diseased medial layer to the driving force of
      the intraluminal blood. This blood penetrates the diseased medial layer and
      cleaves the media longitudinally, thereby dissecting the aortic wall. Herein, we
      report the case of a 38-year-old woman, who presented with chest pain and
      dyspnea. After physical examination, laboratory evaluation, echocardiography, and
      CT-angiography, extensive aortic dissection was diagnosed involving the
      innominate and left common carotid arteries. Accordingly, the debranching of the
      aortic arch arteries was performed. During the procedure, the patient was
      monitored with bilateral regional cerebral tissue oximetry. The patient did not
      show any signs of complications either in the postoperative period or at
      postoperative three-month weekly follow-up or at subsequent monthly follow-up for
      the past year. 

PMID- 25861326
TI  - Concurrent mobile and in situ types of right heart thrombi.
AB  - Right-sided heart thrombus is a life-threatening condition that necessitates
      immediate therapy. Detection of right-sided heart thrombus is usually via
      transthoracic echocardiography. Generally, thrombolysis is considered a treatment
      of choice, but there is currently no consensus about the optimal therapeutic
      choice. We present a case of multiple right atrial thrombi with concurrent mobile
      and broad-based in situ thrombi in a patient with a history of chronic
      obstructive pulmonary disease, which was completely resolved by thrombolysis
      following a failed Heparin infusion. The patient was sent home in good clinical
      condition and was stable at 3 months' follow-up. 

PMID- 25861327
TI  - Pulmonary hypertension as a rare cause of postoperative chylothorax.
AB  - Chylothorax in adult occurs most commonly in the wake of cardiac and thoracic
      procedures. Injuries to the common thoracic duct in the thorax or its branches in
      the mediastinum, injuries to the thymus tissues, dissection of the superior vena
      cava or ascending aorta, dissection of the aortic arch, disruption of the
      accessory lymphatics in the left or right thorax, and increased pressure in the
      systemic vein exceeding that of the thoracic duct (usually in the superior vena
      cava thrombosis, Glenn Shunt, and hemi-Fontan) have been proposed as the possible
      causes of chylothorax after surgery for congenital heart disease. However,
      pulmonary hypertension is an exceedingly rare cause of chylothorax in adults. We
      present a case of chylothorax after atrial septal defect surgery in a 30-year-old
      female patient with pulmonary hypertension. The postoperative period was
      complicated by chylothorax, which was confirmed by the high lipid content of
      chylous effusion. The patient was treated conservatively with diet therapy, and
      the effusion was abolished completely after two weeks. No recurrence of
      chylothorax was detected at 3 months' follow-up. 

PMID- 25861328
TI  - What is The Next Step When a Non-Compliant Balloon Does Not Pass through a
      Freshly Deployed Stent?

PMID- 25861329
TI  - Nutritional strategy of early amino acid administration in very low birth weight
      infants.
AB  - Relative to a fetus of the same gestational age, very low birth weight (VLBW)
      infants are more likely to be underfed and to undergo growth restriction during
      their early hospital stay. The current trend towards "early and aggressive"
      nutritional strategies in VLBW infants aims to overcome the early nutritional
      deficiency and thereby boost postnatal catch-up growth, simultaneously improving
      long-term neurodevelopmental outcomes. Although the minimum starting amino acid
      (AA) dose to prevent negative nitrogen balance is well established, the upper
      limit and the rate of increase of early AA doses are controversial. Most
      randomized controlled trials show that early and high-dose (target, 3.5 to 4.9
      g/kg/day) AA regimens, with or without high nonprotein calories, do not improve
      long-term growth and neurodevelopment. High-dose AA supplementation may lead to
      early metabolic disturbances and excessive or disproportionate plasma AA levels,
      particularly in infants of very low gestational age. Further large studies are
      needed to clarify the optimal strategy for early administration of parenteral AA
      doses in VLBW infants. 

PMID- 25861330
TI  - Update of genetic susceptibility in patients with Kawasaki disease.
AB  - Kawasaki disease (KD) is an acute systemic vasculitis that predominantly affects
      children, and can result in coronary artery lesions (CAL). A patient with KD who
      is resistant to treatment with intravenous immunoglobulin (IVIG) has a higher
      risk of developing CAL. Incomplete KD has increased in prevalence in recent
      years, and is another risk factor for the development of CAL. Although the
      pathogenesis of KD remains unclear, there has been increasing evidence for the
      role of genetic susceptibility to the disease since it was discovered in 1967. We
      retrospectively reviewed previous genetic research for known susceptibility genes
      in the pathogenesis of KD, IVIG resistance, and the development of CAL. This
      review revealed numerous potential susceptibility genes including genetic
      polymorphisms of ITPKC, CASP3, the transforming growth factor-beta signaling
      pathway, B lymphoid tyrosine kinase, FCGR2A, KCNN2, and other genes, an imbalance
      of Th17/Treg, and a range of suggested future treatment options. The results of
      genetic research may improve our understanding of the pathogenesis of KD, and aid
      in the discovery of new treatment modalities for high-risk patients with KD. 

PMID- 25861331
TI  - House dust mite-specific immunoglobulin E and longitudinal exhaled nitric oxide
      measurements in children with atopic asthma.
AB  - PURPOSE: House dust mite (HDM) has been suggested to be the most important
      aeroallergen responsible for atopic asthma in Korea. We aimed to investigate that
      specific IgE antibodies to HDM and other common indoor aeroallergens contribute
      differently to total serum IgE and show different relationships with longitudinal
      fractional exhaled nitric oxide (FeNO) measurements in Korean atopic asthmatic
      patients. METHODS: A total of 193 children aged 8 to 16 years with intermittent
      or mild persistent atopic asthma were recruited. Sera were assayed for total IgE
      and specific IgE antibodies to HDM and other common indoor allergens. FeNO was
      serially measured 10 times or more over 2 years when subjects were not receiving
      controller medications. RESULTS: In 152 children who completed the study, IgE
      antibodies to specific HDM were more prevalent than those to other common indoor
      aeroallergens. In addition, IgE antibody titers to HDM were the strongest
      contributor to total IgE increases. Furthermore, only HDM-specific IgE antibody
      titer significantly correlated with maximum FeNO (r=0.21, P=0.029) and the rate
      of FeNO higher than 21 parts per billion (ppb) (r=0.30, P=0.002). Eight patients
      (5%) were found to have maximum FeNO of 21 ppb or less, suggesting the presence
      of a low FeNO phenotype among atopic asthmatic patients. CONCLUSION: The quantity
      of HDM-specific IgE antibody provides a possible explanation for increases of
      total IgE and significantly correlates with the amount and frequency of FeNO
      increases in Korean atopic asthmatic patients.

PMID- 25861332
TI  - Relationship between serum 25-hydroxyvitamin D and interleukin-31 levels, and the
      severity of atopic dermatitis in children.
AB  - PURPOSE: Atopic dermatitis (AD) is a chronic inflammatory relapsing skin
      disorder. Vitamin D plays a pivotal role in the development of AD, and
      interleukin (IL) 31 is known to be related to pruritus in AD. The aim of our
      study was to determine whether 25-hydroxyvitamin D (25(OH)D) levels are related
      to IL-31 levels or to the severity of AD. METHODS: We enrolled 91 children with
      AD and 32 control subjects without history or symptoms of allergic diseases.
      Blood was drawn to evaluate complete blood cell count, total eosinophil count
      (TEC), and total IgE, specific IgE to common allergens, 25(OH)D, and IL-31
      levels. Serum 25(OH)D and IL-31 levels were measured using high-performance
      liquid chromatography and enzyme-linked immunosorbent assay, respectively. The
      scoring atopic dermatitis (SCORAD) index was used to evaluate the severity of AD.
      RESULTS: The mean 25(OH)D level was significantly lower in the AD group than in
      the control group; 25(OH)D decreased greatly in the moderate and severe AD groups
      compared with the mild AD group. Children with atopic sensitization showed
      significantly lower 25(OH)D levels than nonatopic children. However, serum IL-31
      levels were not related to AD group, SCORAD index, or 25(OH)D levels. The SCORAD
      index was inversely correlated with serum 25(OH)D level and positively correlated
      with TECs and total IgE levels. Children with moderate and severe AD had
      significantly higher TECs than children with mild AD. CONCLUSION: Vitamin D is
      related to the severity of AD independently of IL-31.

PMID- 25861333
TI  - Prevalence of human parechovirus and enterovirus in cerebrospinal fluid samples
      in children in Jinju, Korea.
AB  - PURPOSE: Human parechovirus (HPeV) and enterovirus (EV) are causative agents of a
      sepsis-like illness in neonates and of infections of the central nervous system
      in young children. The objectives of this study were to assess the prevalence of
      HPeV3 and EV infection in young children with a sepsis-like illness or with
      meningitis in Jinju, Korea. METHODS: Cerebrospinal fluid (CSF) samples were
      collected from 267 patients (age range, 1 day to 5 years) and assessed for HPeV
      and EV by performing reverse transcription polymerase chain reaction assay.
      Amplification products of the VP3/VP1 region of HPeV and of the VP1 region of EV
      were sequenced to identify the virus type. RESULTS: HPeV and EV were detected in
      3.4% and 7.5% of the total CSF samples assessed, respectively. The age
      distribution of EV-positive patients (median age, 1.4 months) had a significantly
      broader range than that of HPeV-positive patients (median age, 7.8 months). The
      peak seasons for HPeV and EV infection were spring and summer, respectively. The
      clinical symptoms for HPeV and EV infection were similar, and fever was the most
      common symptom. Pleocytosis was detected in 22.2% of HPeV-positive patients and
      35.5% of EV-positive patients. The VP3/VP1 gene sequence of the nine Korean
      strains clustered most closely with the Japanese strain (AB759202). CONCLUSION:
      The data indicate that HPeV infection is predominant in young infants (<6 months)
      and that meningitis without pleocytosis was caused by both HPeV and EV infection
      in children.

PMID- 25861334
TI  - DiGeorge syndrome who developed lymphoproliferative mediastinal mass.
AB  - DiGeorge syndrome is an immunodeficient disease associated with abnormal
      development of 3rd and 4th pharyngeal pouches. As a hemizygous deletion of
      chromosome 22q11.2 occurs, various clinical phenotypes are shown with a broad
      spectrum. Conotruncal cardiac anomalies, hypoplastic thymus, and hypocalcemia are
      the classic triad of DiGeorge syndrome. As this syndrome is characterized by
      hypoplastic or aplastic thymus, there are missing thymic shadow on their plain
      chest x-ray. Immunodeficient patients are traditionally known to be at an
      increased risk for malignancy, especially lymphoma. We experienced a 7-year-old
      DiGeorge syndrome patient with mediastinal mass shadow on her plain chest x-ray.
      She visited Severance Children's Hospital hospital with recurrent pneumonia, and
      throughout her repeated chest x-ray, there was a mass like shadow on anterior
      mediastinal area. We did full evaluation including chest computed tomography,
      chest ultrasonography, and chest magnetic resonance imaging. To rule out
      malignancy, video assisted thoracoscopic surgery was done. Final diagnosis of the
      mass which was thought to be malignancy, was lymphoproliferative lesion. 

PMID- 25861335
TI  - Massive pulmonary hemorrhage in enterovirus 71-infected hand, foot, and mouth
      disease.
AB  - Hand, foot, and mouth disease (HFMD) is an acute, mostly self-limiting infection.
      Patients usually recover without any sequelae. However, a few cases are life
      threatening, especially those caused by enterovirus 71 (EV71). A 12-month-old boy
      was admitted to a primary hospital with high fever and vesicular lesions of the
      mouth, hands, and feet. After 3 days, he experienced 3 seizure episodes and was
      referred to our hospital. On admission, he was conscious and his chest radiograph
      was normal. However, 6 hours later, he suddenly lost consciousness and had
      developed a massive pulmonary hemorrhage that continued until his death. He
      experienced several more intermittent seizures, and diffuse infiltration of both
      lung fields was observed on chest radiography. Intravenous immunoglobulin,
      dexamethasone, cefotaxime, leukocyte-depleted red blood cells, fresh frozen
      plasma, inotropics, vitamin K, and endotracheal epinephrine were administered.
      The patient died 9 hours after intubation, within 3 days from fever onset. EV71
      subgenotype C4a was isolated retrospectively from serum and nasopharyngeal swab
      by real-time reverse transcription-polymerase chain reaction. Here, we report a
      fatal case of EV71-associated HFMD with sudden-onset massive pulmonary hemorrhage
      and suspected encephalitis. 

PMID- 25861336
TI  - Diagnosis and treatment of extrapulmonary tuberculosis.
AB  - Extrapulmonary tuberculosis (EPTB) constitutes about 20% of all cases of
      tuberculosis (TB) in Korea. Diagnosing EPTB remains challenging because clinical
      samples obtained from relatively inaccessible sites may be paucibacillary, thus
      decreasing the sensitivity of diagnostic tests. Whenever practical, every effort
      should be made to obtain appropriate specimens for both mycobacteriologic and
      histopathologic examinations. The measurement of biochemical markers in TB
      affected serosal fluids (adenosine deaminase or gamma interferon) and molecular
      biology techniques such as polymerase chain reaction may be useful adjuncts in
      the diagnosis of EPTB. Although the disease usually responds to standard anti-TB
      drug therapy, the ideal regimen and duration of treatment have not yet been
      established. A paradoxical response frequently occurs during anti-TB therapy. It
      should be distinguished from other causes of clinical deterioration. Surgery is
      required mainly to obtain valid diagnostic specimens and to manage complications.
      Because smear microscopy or culture is not available to monitor patients with
      EPTB, clinical monitoring is the usual way to assess the response to treatment. 

PMID- 25861337
TI  - Diagnosis and treatment of latent tuberculosis infection.
AB  - A small number of viable tuberculosis bacilli can reside in an individual with
      latent tuberculosis infection (LTBI) without obvious clinical symptoms or
      abnormal chest radiographs. Diagnosis and treatment for LTBI are important for
      tuberculosis (TB) control in public and private health, especially in high-risk
      populations. The updated 2014 Korean guidelines for TB recommend that tuberculin
      skin tests, interferon-gamma release assays, or a combination of the two can be
      used for LTBI diagnosis according to age and immune status of the host as well as
      TB contact history. The regimens for LTBI treatment include isoniazid,
      rifampicin, or isoniazid/rifampicin. However, results of drug susceptibility test
      from the index case must be considered in selecting the appropriate drug for
      recent contacts. Standardized LTBI diagnosis and treatment based on the new 2014
      guidelines will contribute to the effective TB control in Korea as well as to the
      establishment of updated guidelines. 

PMID- 25861338
TI  - Diagnosis of pulmonary tuberculosis: recent advances and diagnostic algorithms.
AB  - Pulmonary tuberculosis (TB) persists as a great public health problem in Korea.
      Increases in the overall age of the population and the rise of drug-resistant TB
      have reinforced the need for rapid diagnostic improvements and new modalities to
      detect TB and drug-resistant TB, as well as to improve TB control. Standard
      guidelines and recent advances for diagnosing pulmonary TB are summarized in this
      article. An early and accurate diagnosis of pulmonary TB should be established
      using chest X-ray, sputum microscopy, culture in both liquid and solid media, and
      nucleic acid amplification. Chest computed tomography, histopathological
      examination of biopsy samples, and new molecular diagnostic tests can be used for
      earlier and improved diagnoses, especially in patients with smear-negative
      pulmonary TB or clinically-diagnosed TB and drug-resistant TB. 

PMID- 25861339
TI  - Prevalence of benign diseases mimicking lung cancer: experience from a university
      hospital of southern Brazil.
AB  - BACKGROUND: Lung cancer is the most lethal type of cancer in the world. Several
      benign lung diseases may mimic lung carcinoma in its clinical and radiological
      presentation, which makes the differential diagnosis for granulomatous diseases
      more relevant in endemic regions like Brazil. This study was designed to describe
      the prevalence and the diagnostic work-up of benign diseases that mimic primary
      lung cancer in patients hospitalized at a university hospital from south of
      Brazil. METHODS: This was a transversal study, which evaluated the medical
      records of 1,056 patients hospitalized for lung cancer treatment from September
      2003 to September 2013 at University Hospital of Santa Maria. RESULTS: Eight
      hundred and four patients underwent invasive procedures for suspected primary
      lung carcinoma. Primary lung cancer was confirmed in 77.4% of the patients.
      Benign disease was confirmed in 8% of all patients. Tuberculosis (n=14) and
      paracoccidioidomycosis (n=9) were the most frequent infectious diseases. The
      diagnosis of benign diseases was obtained by flexible bronchoscopy in 55.6% of
      the cases and by thoracotomy in 33.4%. CONCLUSION: Infectious diseases are the
      most frequent benign diseases mimicking lung cancer at their initial
      presentation. Many of these cases could be diagnosed by minimally invasive
      procedures such as flexible bronchoscopy. Benign diseases should be included in
      the differential diagnosis during the investigation for primary lung cancer in
      order to avoid higher cost procedures and mortality.

PMID- 25861340
TI  - Outcomes and use of therapeutic drug monitoring in multidrug-resistant
      tuberculosis patients treated in virginia, 2009-2014.
AB  - BACKGROUND: Reports of therapeutic drug monitoring (TDM) for second-line
      medications to treat multidrug-resistant tuberculosis (MDR-TB) remain limited.
      METHODS: A retrospective cohort from the Virginia state tuberculosis (TB)
      registry, 2009-2014, was analyzed for TDM usage in MDR-TB. Drug concentrations,
      measured at time of estimated peak (Cmax), were compared to expected ranges.
      RESULTS: Of 10 patients with MDR-TB, 8 (80%) had TDM for at least one drug
      (maximum 6 drugs). Second-line drugs tested were cycloserine in seven patients
      (mean C2hr, 16.6+/-10.2 ug/mL; 4 [57%] below expected range); moxifloxacin in
      five (mean C2hr, 3.2+/-1.5 ug/mL; 1 [20%] below); capreomycin in five (mean C2hr,
      21.5+/-14.0 ug/mL; 3 [60%] below); para-aminosalicylic acid in five (mean C6hr,
      65.0+/-29.1 ug/mL; all within or above); linezolid in three (mean C2hr, 11.4+/
      4.1 ug/mL, 1 [33%] below); amikacin in two (mean C2hr, 35.3+/-3.7 ug/mL; 1 [50%]
      below); ethionamide in one (C2hr, 1.49 ug/mL, within expected). Two patients
      died: a 38-year-old woman with human immunodeficiency virus/acquired immune
      deficiency syndrome and TB meningitis without TDM, and a 76-year-old man with
      fluoroquinolone-resistant (pre-extensively drug-resistant) pulmonary TB and low
      linezolid and capreomycin concentrations. CONCLUSION: Individual pharmacokinetic
      variability was common. A more standardized approach to TDM for MDR-TB may limit
      over-testing and maximize therapeutic gain.

PMID- 25861341
TI  - Does the Mean Arterial Pressure Influence Mortality Rate in Patients with Acute
      Hypoxemic Respiratory Failure under Mechanical Ventilation?
AB  - BACKGROUND: In sepsis patients, target mean arterial pressures (MAPs) greater
      than 65 mm Hg are recommended. However, there is no such recommendation for
      patients receiving mechanical ventilation. We aimed to evaluate the influence of
      MAP over the first 24 hours after intensive care unit (ICU) admission on the
      mortality rate at 60 days post-admission in patients showing acute hypoxemic
      respiratory failure under mechanical ventilation. METHODS: This prospective,
      multicenter study included 22 ICUs and compared the mortality and clinical
      outcomes in patients showing acute hypoxemic respiratory failure with high (75-90
      mm Hg) and low (65-74.9 mm Hg) MAPs over the first 24 hours of admission to the
      ICU. RESULTS: Of the 844 patients with acute hypoxemic respiratory failure, 338
      had a sustained MAP of 65-90 mm Hg over the first 24 hours of admission to the
      ICU. At 60 days, the mortality rates in the low (26.2%) and high (24.5%) MAP
      groups were not significantly different. The ICU days, hospital days, and 60-day
      mortality rate did not differ between the groups. CONCLUSION: In the first 24
      hours of ICU admission, MAP range between 65 and 90 mm Hg in patients with acute
      hypoxemic respiratory failure under mechanical ventilation may not cause
      significantly differences in 60-day mortality.

PMID- 25861342
TI  - Seven-day continuous abstinence rate from smoking at 1, 2, or 3 years after the
      use of varenicline.
AB  - BACKGROUND: Varenicline, a selective partial agonist/antagonist of the
      alpha4beta2 nicotinic receptor, has proven effectiveness for smoking cessation by
      several randomized, controlled trials. Because few studies have evaluated the
      long-term efficacy of varenicline, we tried to evaluate the smoking status of
      varenicline users up to 3 years after the initial prescription of the drug.
      METHODS: We interviewed varenicline users who were prescribed the drug from June
      2007 to May 2010 by telephone, from June 2010 to May 2011. RESULTS: One-hundred
      and thirty-three of 250 varenicline users (53.2%) were available for the survey.
      Seven-day continuous abstinence from smoking was adhered to by 17 of 39
      respondents (43.6%) at 1 year, and 11 of 36 (30.6%) and 19 of 58 (32.8%) at 2 and
      3 years since the first use of varenicline, respectively. Compared to current
      smokers, successful quitters were older (55.0 years vs. 49.9 years, p=0.01), had
      better compliance to the 12-week course (27.7 vs. 9.3%, p=0.01), and had taken
      varenicline longer (10.1 vs. 5.9 weeks, p=0.01). Fifty-four of 71 current smokers
      (76.1%) were willing to stop smoking in the near future. The preferred ways to
      cease smoking were will-power (48.1%), varenicline (25.9%), nicotine replacement
      therapy (11.1%), and others (14.9%). CONCLUSION: Smokers should be encouraged to
      stick to the proven way for recommended period of time for successful cessation
      of smoking.

PMID- 25861343
TI  - Regulation of CYP1A1 and Inflammatory Cytokine by NCOA7 Isoform 4 in Response to
      Dioxin Induced Airway Inflammation.
AB  - BACKGROUND: Aryl hydrocarbon receptor (AhR), a ligand-dependent transcription
      factor, binds to a wide variety of synthetic and naturally occurring compounds.
      AhR is involved in the regulation of inflammatory response during acute and
      chronic respiratory diseases. We investigated whether nuclear receptor
      coactivator 7 (NCOA7) could regulate transcriptional levels of AhR target genes
      and inflammatory cytokines in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-treated
      human bronchial epithelial cells. This study was based on our previous study that
      NCOA7 was differentially expressed between normal and chronic obstructive
      pulmonary disease lung tissues. METHODS: BEAS-2B and A549 cells grown under serum
      free conditions were treated with or without TCDD (0.15 nM and 6.5 nM) for 24
      hours after transfection of pCMV-NCOA7 isoform 4. Expression levels of cytochrome
      P4501A1 (CYP1A1), IL-6, and IL-8 were measured by quantitative real-time
      polymerase chain reaction. RESULTS: The transcriptional activities of CYP1A1 and
      inflammatory cytokines were strongly induced by TCDD treatment in both BEAS-2B
      and A549 cell lines. The NCOA7 isoform 4 oppositely regulated the transcriptional
      activities of CYP1A1 and inflammatory cytokines between BEAS-2B and A549 cell
      lines. CONCLUSION: Our results suggest that NCOA7 could act as a regulator in the
      TCDD-AhR signaling pathway with dual roles in normal and abnormal physiological
      conditions.

PMID- 25861344
TI  - Massive Hemoptysis due to Endotracheal Hemangioma: A Case Report and Literature
      Review.
AB  - Tracheal hemangioma is a rare benign vascular tumor in adults. We reported a case
      of massive hemoptysis caused by a cavernous hemangioma in a 75-year-old man. This
      is the first report, to our knowledge, of a tracheal cavernous hemangioma that
      presented with massive hemoptysis. The lesion was removed with a CO2 laser under
      rigid laryngoscopy. Endovascular tumors, such as tracheobronchial hemangiomas,
      should be considered a diagnostic option in cases of massive hemoptysis without a
      significant underlying lung lesion. 

PMID- 25861345
TI  - A rare case of primary thymic adenocarcinoma mimicking small cell lung cancer.
AB  - Primary thymic adenocarcinoma is a very rare malignancy of the anterior
      mediastinum with no standardized treatment. A 36-year-old male patient presented
      with hoarseness over the past 3 months. A chest computed tomography (CT) scan
      showed an infiltrative mass to the proximal vessels and aortic arch in left upper
      mediastinum (4.1*3.1*5.4 cm). Brain magnetic resonance imaging (MRI) showed focal
      lesions, suggesting metastasis in the left frontal lobe. A thoracoscopic biopsy
      of the mediastinal mass confirmed a primary thymic adenocarcinoma forming a
      glandular structure with atypia of tumor cells. The patient received four cycles
      of systemic chemotherapy, consisting of etoposide and cisplatin, with concurrent
      radiotherapy (6,000 cGy/30 fractions) to the mediastinal lesion and the
      metastatic brain lesion (4,200 cGy/12 fractions). A follow-up chest CT scan and
      brain MRI showed a decrease in the size of the left upper mediastinal mass and
      brain lesion. We report a rare case of the primary thymic adenocarcinoma with a
      literature review. 

PMID- 25861346
TI  - A case of solitary fibrous pleura tumor associated with severe hypoglycemia:
      doege-potter syndrome.
AB  - Solitary fibrous tumor of the pleura (SFTP) is a rare primary intrathoracic tumor
      that arises from mesenchymal tissue underlying the mesothelial layer of the
      pleura. It usually has an indolent clinical course. The hypoglycemia that
      accompanies SFTP was first described by Doege and Potter independently in 1930,
      hence the eponym Doege-Potter syndrome (DPS). The incidence of DPS is reported to
      be ~4%. In this report, we present a typical case of DPS that was cured through
      complete surgical resection. 

PMID- 25861347
TI  - Agranulocytosis induced by ethambutol in a patient with pulmonary tuberculosis.
AB  - We report a case of agranulocytosis caused by ethambutol in a 79-year-old man
      with pulmonary tuberculosis. He was referred for fever and skin rash developed on
      21th day after antituberculosis drugs (isoniazid, rifampicin, ethambutol, and
      pyrazinamide) intake. Complete blood count at the time of diagnosis of pulmonary
      tuberculosis was normal. On the seventh admission day, agranulocytosis was
      developed with absolute neutrophil count of 70/uL. We discontinued all
      antituberculosis drugs, and then treated with granulocyte colony-stimulating
      factor. Three days later, the number of white blood cell returned to normal. We
      administered isoniazid, pyrazinamide, and ethambutol in order with an interval.
      However, fever and skin rash developed again when adding ethambutol, so we
      discontinued ethambutol. After these symptoms disappeared, we added rifampicin
      and ethambutol in order with an interval. However after administering ethambutol,
      neutropenia developed, so we discontinued ethambutol again. He was cured with
      isoniazid, rifampicin, and pyrazinamide for 9 months. 

PMID- 25861348
TI  - Two cases of bronchopulmonary dysplasia of similar appearance in adult
      monozygotic twin: pathology and computed tomographic findings.
AB  - Bronchopulmonary dysplasia (BPD) is related to decreased lung function throughout
      life. However, the pathology and radiology pattern of BPD of adults are not
      documented well yet. In this case report, we present BPD case of an adult
      monozygotic twin showing nearly identical lesions on chest computed tomography
      (CT). CT images showed mixed areas of ground-glass and reticular opacities in
      both lungs. They had common histories of pneumonias requiring mechanical
      ventilations in period of infants. Pulmonary function test of one patient showed
      a pulmonary insufficiency with airway obstruction. Pathologic findings showed
      bronchiolar hyperplasia and peribronchiolar fibrosis which was similar to classic
      BPD patients. Our twin case report might help provide distinguishing pathology
      and radiology pattern of an adult pulmonary sequelaes of BPD. It might be
      reasonable to make close follow-up for BPD patients to evaluate the long-term
      outcomes of BPD survivors. 

PMID- 25861349
TI  - Allergic Bronchopulmonary Aspergillosis Presenting as Recurrent Mass-like
      Consolidation.
AB  - Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitive disease
      showing various radiographic and clinical manifestations. Its clinical course has
      not been fully understood. Here I describe a case of a 23-year-old
      immunocompetent man with frequently relapsing ABPA. He was asthmatic. He visited
      our hospital because of a chronic cough. Laboratory examination showed
      eosinophilia with increased total and Aspergillus-specific IgE as well as
      positive skin reaction to Aspergillus fumigatus. Radiologic feature was a dense
      consolidation. Histology showed organizing pneumonia with eosinophilic
      infiltration. On the diagnosis of ABPA, he was treated with systemic steroid and
      itraconazole. Although treatment response was excellent, he suffered from
      recurrent ABPA three times thereafter in the form of fleeting mass-like
      consolidation. 

PMID- 25861350
TI  - Low grade pulmonary lymphomatoid granulomatosis with an endobronchial mass.
AB  - Lymphomatoid granulomatosis (LYG) is an angiocentric and angiodestructive
      neoplastic proliferation of B and T lymphocytes commonly involving the lungs.
      Epstein-Barr virus is commonly detected in lesional cells. We report a case of a
      54-year-old female with underlying monoclonal gammopathy of unknown significance
      who presented with a 4 week history of dyspnea and cough. Computed tomography
      scan of the chest showed multiple lung nodules as well as endobronchial narrowing
      causing atelectasis at the left upper lobe. Bronchoscopic findings revealed
      obstruction at the lingula segment due to endobronchial mass as a rare
      presentation. Bronchoscopic biopsy was diagnosed with LYG grade 1. After
      treatment, the endobronchial mass and lung lesions were completely resolved.
      However, the patient eventually evolved to malignant lymphoma after 1 year. 

PMID- 25861351
TI  - Medicinal plants for the treatment of hypertrophic scars.
AB  - Hypertrophic scar is a complication of wound healing and has a high recurrence
      rate which can lead to significant abnormity in aesthetics and functions. To
      date, no ideal treatment method has been established. Meanwhile, the underlying
      mechanism of hypertrophic scarring has not been clearly defined. Although a large
      amount of scientific research has been reported on the use of medicinal plants as
      a natural source of treatment for hypertrophic scarring, it is currently
      scattered across a wide range of publications. Therefore, a systematic summary
      and knowledge for future prospects are necessary to facilitate further medicinal
      plant research for their potential use as antihypertrophic scar agents. A
      bibliographic investigation was accomplished by focusing on medicinal plants
      which have been scientifically tested in vitro and/or in vivo and proved as
      potential agents for the treatment of hypertrophic scars. Although the chemical
      components and mechanisms of action of medicinal plants with antihypertrophic
      scarring potential have been investigated, many others remain unknown. More
      investigations and clinical trials are necessary to make use of these medical
      plants reasonably and phytotherapy is a promising therapeutic approach against
      hypertrophic scars. 

PMID- 25861352
TI  - Effects of moderate exercise on relieving mental load of elementary school
      teachers.
AB  - Long-term endurance exercise could increase activity of parasympathetic nervous
      and decrease activity of sympathetic nervous at rest. However, previous studies
      all focused on the effect of endurance training on heart rate variability (HRV)
      for athletes or sedentary subjects. In Taiwan, elementary school teachers
      teaching and processing the children's and administrative problems always stand
      and walk. They will sit down only when they review and correct the students' home
      work. Thus, the goal of this study was to elucidate the beneficial effect of
      moderate intensity exercise on relieving mental load of elementary school
      teachers. There were 20 participants in the exercise group and another 20
      participants in the nonexercise group. The exercising teachers performed 12 weeks
      of moderate intensity exercise training for an average of 30 minutes per day, 3
      times per week. HRV was measured before and after the 4th, 6th, and 12th weeks.
      The time and frequency domain parameters of HRV all had significant increases
      between the beginning and after 12 weeks of training. However, the time and
      frequency domain parameters of HRV in the nonexercise group had significant
      decreases between the beginning and after 12 weeks of training. The long-term
      moderate exercises can relieve mental load of elementary school teachers.
      Moreover, age was the considerable factor affecting HRV in this study. 

PMID- 25861353
TI  - MicroRNA Profiling Response to Acupuncture Therapy in Spontaneously Hypertensive
      Rats.
AB  - MicroRNAs (miRNAs) are a group of endogenous noncoding RNAs that play important
      roles in many biological processes. This study aimed to check if miRNAs were
      involved in the response to acupuncture in rats. Microarray analysis was
      performed to compare the miRNA expression profiles of medulla in spontaneously
      hypertensive rats (SHRs) treated with or without acupuncture. Our microarray
      analysis identified 222 differentially expressed miRNAs in the medulla of SHRs
      treated with acupuncture at taichong acupoint. Among these miRNAs, 23 miRNAs with
      a significant difference were found in acupuncture-treated SHRs compared to
      untreated rats. These 23 miRNAs could regulate 2963 target genes which were
      enriched in at least 14 pathways based on our bioinformatic analysis. miRNA-339,
      miR-223, and miR-145 were downregulated in the medulla of SHRs compared to
      normotensive rats. Notably, these miRNAs were upregulated to basal levels in the
      medulla of SHRs treated with acupuncture at taichong in comparison with SHRs
      receiving acupuncture at nonacupoint group or SHRs without any treatment. Our
      findings have revealed significant changes of a panel of selective miRNAs in
      hypertensive rats treated at taichong acupoint. These data provide insights into
      how acupuncture elicits beneficial effects on hypertension. 

PMID- 25861354
TI  - Do herbal formulas influence the international normalized ratio of patients
      taking warfarin? A retrospective study.
AB  - Warfarin is a common anticoagulant agent for cardiovascular diseases, and it is
      known to interact with several foods and drugs. Several studies report an
      interaction between warfarin and herbal medicines; however, the influence of
      herbal medicines on the international normalized ratio (INR) is still
      controversial. We investigated the influence of herbal formulas on INR of
      patients taking warfarin. We searched electronic medical records of inpatients
      for INR results. Then, we compared the changes in INR and any adverse events
      between the group taking herbal formulas and warfarin (herbal group) and another
      group taking warfarin only (nonherbal group). Eighty-six patients were included;
      45 patients were assigned to the herbal group and 41 patients to the nonherbal
      group. The herbal group had taken the same dose of warfarin for a longer period.
      The nonherbal group had a slightly higher mean INR value than the herbal group.
      The ratio of INR less than 2 and greater than 3, the ratio of INR that increased
      or decreased by one or more compared to the initial INR, and the ratio of adverse
      events were not significantly different between the two groups. It is suggested
      that use of herbal formulas may not influence INR value. 

PMID- 25861356
TI  - Monitoring the Effects of Acupoint Antioxidant Intervention by Measuring
      Electrical Potential Difference along the Meridian.
AB  - Previous studies suggest that superoxide anions are possibly traveling along
      acupuncture meridians. The electrical potential difference (EPD) between
      acupoints may be related to the movement. To test the above hypothesis, we
      conducted a study investigating the effects of acupoint antioxidant interventions
      on the meridian EPD. Firstly, ST39 (L) and ST44 (L) were screened out for the EPD
      detection along the stomach meridian, and ST36 (L) was selected for interventions
      including acumassage with the control cream, as well as the TAT-SOD cream for 30
      minutes, or injection with reduced glutathione sodium. The EPD between ST39 and
      ST44 was recorded for 80 minutes and measured again 48 h later. While the EPD
      increased during the acumassage, the acumassage with TAT-SOD cream and the
      glutathione injection generated waves of EPD increased, indicating the migration
      or removal from the visceral organ of a greater quantity of superoxide.
      Remarkably lower EPD readings 48 h later with both antioxidant acupoint
      interventions than the mere acumassage imply a more complete superoxide flushing
      out due to the restored superoxide pathway at the acupoint after interventions.
      The results confirm superoxide transportation along the meridians and demonstrate
      a possibility of acupoint EPD measurement as a tool to monitor changes in the
      meridians and acupoints. 

PMID- 25861355
TI  - Alternative antimicrobial approach: nano-antimicrobial materials.
AB  - Despite numerous existing potent antibiotics and other antimicrobial means,
      bacterial infections are still a major cause of morbidity and mortality.
      Moreover, the need to develop additional bactericidal means has significantly
      increased due to the growing concern regarding multidrug-resistant bacterial
      strains and biofilm associated infections. Consequently, attention has been
      especially devoted to new and emerging nanoparticle-based materials in the field
      of antimicrobial chemotherapy. The present review discusses the activities of
      nanoparticles as an antimicrobial means, their mode of action, nanoparticle
      effect on drug-resistant bacteria, and the risks attendant on their use as
      antibacterial agents. Factors contributing to nanoparticle performance in the
      clinical setting, their unique properties, and mechanism of action as
      antibacterial agents are discussed in detail. 

PMID- 25861357
TI  - Antiviral Action of Hydromethanolic Extract of Geopropolis from Scaptotrigona
      postica against Antiherpes Simplex Virus (HSV-1).
AB  - The studies on chemical composition and biological activity of propolis had
      focused mainly on species Apis mellifera L. (Hymenoptera: Apidae). There are few
      studies about the uncommon propolis collected by stingless bees of the Meliponini
      tribe known as geopropolis. The geopropolis from Scaptotrigona postica was
      collected in the region of Barra do Corda, Maranhao state, Brazil. The chemical
      analysis of hydromethanolic extract of this geopropolis (HMG) was carried out
      through HPLC-DAD-ESI-MS/MS and the main constituents found were pyrrolizidine
      alkaloids and C-glycosyl flavones. The presence of alkaloids in extracts of
      propolis is detected for the first time in this sample. The antiviral activity of
      HMG was evaluated through viral DNA quantification experiments and electron
      microscopy experiments. Quantification of viral DNA from herpes virus showed
      reduction of about 98% in all conditions and concentration tested of the HMG
      extract. The results obtained were corroborated by transmission electron
      microscopy, in which the images did not show particle or viral replication
      complex. The antiviral activity of C-glycosyl flavones was reported for a variety
      of viruses, being observed at different points in the viral replication. This
      work is the first report about the antiviral activity of geopropolis from
      Scaptotrigona postica, in vitro, against antiherpes simplex virus (HSV). 

PMID- 25861358
TI  - Bee pollen: chemical composition and therapeutic application.
AB  - Bee pollen is a valuable apitherapeutic product greatly appreciated by the
      natural medicine because of its potential medical and nutritional applications.
      It demonstrates a series of actions such as antifungal, antimicrobial, antiviral,
      anti-inflammatory, hepatoprotective, anticancer immunostimulating, and local
      analgesic. Its radical scavenging potential has also been reported. Beneficial
      properties of bee pollen and the validity for their therapeutic use in various
      pathological condition have been discussed in this study and with the currently
      known mechanisms, by which bee pollen modulates burn wound healing process. 

PMID- 25861359
TI  - Natural products for the treatment of obesity, metabolic syndrome, and type 2
      diabetes 2014.

PMID- 25861360
TI  - Differences between Male and Female Consumers of Complementary and Alternative
      Medicine in a National US Population: A Secondary Analysis of 2012 NIHS Data.
AB  - We examined the National Health Interview Survey (NHIS) 2012 to explore how US
      adult consumers of CAM differ by gender in terms of their sociodemographic
      characteristics, current health conditions, and perceived benefits of CAM. All
      individuals who completed the adults core interviews (N = 34,525) were included.
      CAM use, major sociodemographic variables, perceived benefits of using CAM, and
      top ten reported health conditions for which CAM was used were selected and
      analyzed by Stata. Findings revealed that 29.6% (n = 10,181) reported having used
      at least one form of CAM in the previous 12 months. Compared to male CAM users,
      female CAM users were more likely to have a bachelor degree, to be
      divorced/separated or widowed, and less likely to earn $75,000 or more. Back
      pain/problem was the most common problem reported by both male and female CAM
      users (32.2% and 22.6%, resp.). A higher proportion of female CAM users reported
      using CAM for perceived benefits such as general wellness or general disease
      prevention. This paper provides foundation information regarding gender
      differences in CAM use and is a platform for further in-depth examination into
      how and why males and females differ in their reasons for CAM use. 

PMID- 25861361
TI  - Effect of QiShenYiQi Pill on Myocardial Collagen Metabolism in Rats with Partial
      Abdominal Aortic Coarctation.
AB  - This study investigated the effect of QiShenYiQi pill (QSYQ) on myocardial
      collagen metabolism in rats with partial abdominal aortic coarctation and
      explored its mechanism of action. A series of assays were used to detect the
      effect and mechanism of QSYQ on systolic blood pressure, heart mass index, left
      ventricle mass index, HYP, expression of PICP, PIIINT, and CTX-I in serum, MMP-1,
      and TIMP-1 expression in myocardium. We observed that QSYQ can reduce the rate of
      myocardial collagen synthesis and increase the rate of myocardial collagen
      degradation. It also effectively improved the degree of myocardial fibrosis in
      partial abdominal aortic rats and it had a tendency to have a greater effect with
      longer treatment duration, which is related to the mechanism of regulation of MMP
      1 and TIMP-1 expression in the myocardial rat. 

PMID- 25861362
TI  - Preliminary Studies of the Immunomodulator Effect of the Bougainvillea xbuttiana
      Extract in a Mouse Model.
AB  - Bougainvillea xbuttiana is used as an analgesic in folk medicine in Mexico. The
      purpose of the present study was to determine the effects of the ethanolic
      extract from B. xbuttiana on macrophages activities. The phytochemical screening
      was performed for determine the presence of alkaloids, flavonoids, triterpenes,
      and saponins. The effects of B. xbuttiana were analyzed using the macrophages
      activities as determined by the H2O2 release, spreading and phagocytic index,
      vacuoles formation percentage, and mediators production. The viability percentage
      was determined in live cells after fixing and staining with crystal violet. The
      presence of H2O2 in macrophages was performed by using the peroxidase-phenol red
      solution. The cytokine production was determined by two assays, ELISA for
      detection of IL-6, IL-10, and IFN-gamma and biological assay for TNF detection.
      The results showed that the Bxb extract dose-dependent manner produces (a) an
      increase in levels of H2O2 and spreading and vacuoles formation percentages, (b)
      a decrease in phagocytic index and in the amounts of TNF, IL-6, and IFN-gamma,
      and (c) an increase significant in IL-10 and NO production. This study indicates
      that the ethanolic extract from Bougainvillea xbuttiana was able to activate
      macrophages. The combination of these results suggests that this extract has an
      immunomodulator effect. 

PMID- 25861363
TI  - A microarray study of middle cerebral occlusion rat brain with acupuncture
      intervention.
AB  - Microarray analysis was used to investigate the changes of gene expression of
      ischemic stroke and acupuncture intervention in middle cerebral artery occlusion
      (MCAo) rat brain. Results showed that acupuncture intervention had a remarkable
      improvement in neural deficit score, cerebral blood flow, and cerebral infarction
      volume of MCAo rats. Microarray analysis showed that a total of 627 different
      expression genes were regulated in ischemic stroke. 417 genes were upregulated
      and 210 genes were downregulated. A total of 361 different expression genes were
      regulated after acupuncture intervention. Three genes were upregulated and 358
      genes were downregulated. The expression of novel genes after acupuncture
      intervention, including Tph1 and Olr883, was further analyzed by Real-Time
      Quantitative Polymerase Chain Reaction (RT-PCR). Upregulation of Tph1 and
      downregulation of Olr883 indicated that the therapeutic effect of acupuncture for
      ischemic stroke may be closely related to the suppression of poststroke
      depression and regulation of olfactory transduction. In conclusion, the present
      study may enrich our understanding of the multiple pathological process of
      ischemic brain injury and indicate possible mechanisms of acupuncture on ischemic
      stroke. 

PMID- 25861365
TI  - TCM Zheng Classification and Clinical Trials 2014.

PMID- 25861364
TI  - An update on oligosaccharides and their esters from traditional chinese
      medicines: chemical structures and biological activities.
AB  - A great number of naturally occurring oligosaccharides and oligosaccharide esters
      have been isolated from traditional Chinese medicinal plants, which are used
      widely in Asia and show prominent curative effects in the prevention and
      treatment of kinds of diseases. Numerous in vitro and in vivo experiments have
      revealed that oligosaccharides and their esters exhibited various activities,
      including antioxidant, antidepressant, cytotoxic, antineoplastic, anti
      inflammatory, neuroprotective, cerebral protective, antidiabetic, plant growth
      regulatory, and immunopotentiating activities. This review summarizes the
      investigations on the distribution, chemical structures, and bioactivities of
      natural oligosaccharides and their esters from traditional Chinese medicines
      between 2003 and 2013. 

PMID- 25861366
TI  - Danggui buxue tang inhibits 2,4-dinitrochlorobenzene: induced atopic dermatitis
      in mice.
AB  - Danggui Buxue Tang (DBT) is a herbal decoction that has been used in Chinese
      medicine to enhance qi and blood circulation. Previously, we found that DBT can
      suppress allergy-related asthma in mice, leading us to hypothesize that DBT might
      ameliorate allergy disease. In this study, we evaluated whether DBT can attenuate
      atopic dermatitis (AD) symptoms and have an anti-inflammatory effect on AD-like
      mice. The dorsal skin of female mice was shaved and sensitized cutaneously (skin
      smear) with 1-chloro-2,4-dinitrobenzene. Mice were then given various doses of
      DBT from days 14 to 29 cutaneously. DBT treatment suppressed ear swelling and
      skin inflammation and decreased mast cell and eosinophil infiltration into skin
      and ear tissue. DBT also inhibited levels of IgE and Th2-associated cytokine
      levels in serum. These results demonstrate that cutaneous administration of DBT
      reduced the development of AD-like skin lesions in mice. 

PMID- 25861367
TI  - Herb-drug pharmacokinetic interaction of a traditional chinese medicine jia-wei
      xiao-yao-san with 5-Fluorouracil in the blood and brain of rat using
      microdialysis.
AB  - According to a survey from the National Health Insurance Research Database
      (NHIRD), Jia-Wei-Xiao-Yao-San (JWXYS) is the most popular Chinese medicine for
      cancer patients in Taiwan. 5-Fluorouracil (5-FU) is a general anticancer drug for
      the chemotherapy. To investigate the herb-drug interaction of JWXYS on
      pharmacokinetics of 5-FU, a microdialysis technique coupled with a high
      performance liquid chromatography system was used to monitor 5-FU in rat blood
      and brain. Rats were divided into four parallel groups, one of which was treated
      with 5-FU (100 mg/kg, i.v.) alone and the remaining three groups were pretreated
      with a different dose of JWXYS (600, 1200, or 2400 mg/kg/day for 5 consecutive
      days) followed by a combination with 5-FU. This study demonstrates that 5-FU with
      JWXYS (600 mg/kg/day or 1200 mg/kg/day) has no significant effect on the
      pharmacokinetics of 5-FU in the blood and brain. However, JWXYS (2400 mg/kg/day)
      coadministered with 5-FU extends the elimination half-life and increases the
      volume of distribution of 5-FU in the blood. The elimination half-life of 5-FU in
      the brain for the pretreatment group with 2400 mg/kg/day of JWXYS is
      significantly longer than that for the group treated with 5-FU alone and also
      reduces the clearance. This study provides practical dosage information for
      clinical practice and proves the safety of 5-FU coadministered with JWXYS. 

PMID- 25861368
TI  - Antiproliferative and Apoptosis Induction Potential of the Methanolic Leaf
      Extract of Holarrhena floribunda (G. Don).
AB  - Natural plant products with potent growth inhibition and apoptosis induction
      properties are extensively being investigated for their cancer chemopreventive
      potential. Holarrhena floribunda (HF) is used in a wide range of traditional
      medicine practices. The present study investigated the antiproliferative and
      apoptosis induction potential of methanolic leaf extracts of HF against breast
      (MCF-7), colorectal (HT-29), and cervical (HeLa) cancer cells relative to normal
      KMST-6 fibroblasts. The MTT assay in conjunction with the trypan blue dye
      exclusion and clonogenic assays were used to determine the effects of the
      extracts on the cells. Caspase activities were assayed with Caspase-Glo 3/7 and
      Caspase-9 kits. Apoptosis induction was monitored by flow cytometry using the
      APOPercentage and Annexin V-FITC kits. Reactive oxygen species (ROS) was measured
      using the fluorogenic molecular probe 5-(and-6)-chloromethyl-2',7'
      dichlorofluorescein diacetate acetyl ester and cell cycle arrest was detected
      with propidium iodide. Dose-response analyses of the extract showed greater
      sensitivity in cancer cell lines than in fibroblast controls. Induction of
      apoptosis, ROS, and cell cycle arrest were time- and dose-dependent for the
      cancer cell lines studied. These findings provide a basis for further studies on
      the isolation, characterization, and mechanistic evaluation of the bioactive
      compounds responsible for the antiproliferative activity of the plant extract. 

PMID- 25861369
TI  - "Like walking into an empty room": effects of eurythmy therapy on stress
      perception in comparison with a sports intervention from the subjects'
      perspective-a qualitative study.
AB  - Background. Stress and health-related quality of life are important constructs
      used in treatment evaluation today. This study is based on a randomised
      controlled trial examining the stress-reducing effect of eurythmy therapy in
      comparison with step aerobics in 106 healthy but stressed subjects. The aim of
      the analysis was to characterise changes in the subjective perceptions of the
      participants. Methods. Interviews were conducted with 76 healthy adults, 36 (f =
      31/m = 5) from the eurythmy group and 40 (f = 28/m = 12) from the step aerobics
      group both analysed by content analysis and phenomenologically. Results. The
      following categories were identified for the eurythmy therapy group: enabling a
      productive therapeutic response, emergence of a new perceptual space,
      reevaluation of the accustomed perception, and emergence of new options for
      action. Step aerobics places increased physical and intellectual demands. These
      are perceived differently as pleasant and relaxing, insufficiently challenging
      and/or boring, and too challenging and thus experienced as stress-enhancing.
      Conclusion. The qualitative results provided revealing insights into the profound
      effects of and subjective assignments of meaning to external and internal stress
      factors. Processes of mental reinterpretation leading to stress reduction can be
      stimulated by physical procedures such as eurythmy therapy. 

PMID- 25861370
TI  - Protective Effect and Mechanism of Total Flavones from Rhododendron simsii Planch
      Flower on Cultured Rat Cardiomyocytes with Anoxia and Reoxygenation.
AB  - Many flavonoids have cardioprotection against myocardial ischemia/reperfusion
      (I/R) injury. Total flavones from Rhododendron simsii Planch flower (TFR) can
      protect myocardial ischemic injuries. However, its protective mechanism is still
      unknown. The present study was designed to investigate the mechanism of TFR on
      myocardial I/R and anoxia/reoxygenation (A/R) injuries. Rat model of myocardial
      I/R injury was made, and myocardial infarction was determined. A/R injury was
      induced in cultured rat cardiomyocytes; cellular damage was evaluated by
      measuring cell viability, LDH and cTnT releases, and MDA content. Expressions of
      ROCK1 and ROCK2 protein were examined by Western blot analysis, and K(+) currents
      were recorded by using whole-cell patch clamp technique. TFR 20~80 mg/kg markedly
      reduced I/R-induced myocardial infarction. TFR 3.7~300 mg/L significantly
      inhibited A/R-induced reduction of cell viability, LDH and cTnT releases, and MDA
      production. Exposure to A/R significantly increased ROCK1 and ROCK2 expressions
      in rat cardiomyocytes, but TFR 33.3~300 mg/L obviously inhibited this increase.
      300 mg/L TFR significantly augmented inward rectifier K(+) current and other K(+)
      currents in rat cardiomyocytes. These results indicate that TFR has a protective
      effect on rat cardiomyocytes A/R damage, and the protective mechanism may be
      engaged with the inhibition of ROCK1 and ROCK2 and activation of K(+) channels. 

PMID- 25861372
TI  - Evaluation of Sedative and Hypnotic Activity of Ethanolic Extract of Scoparia
      dulcis Linn.
AB  - Scoparia dulcis Linn. (SD) is a perennial herb that has been well studied for its
      antioxidant, anti-inflammatory, antidiabetic, and hepatoprotective effects.
      However, scientific information on SD regarding the neuropharmacological effect
      is limited. This study evaluated the sedative and hypnotic effect of the
      ethanolic extract of whole plants of Scoparia dulcis (EESD). For this purpose,
      the whole plants of S. dulcis were extracted with ethanol following maceration
      process and tested for the presence of phytochemical constituents. The sedative
      and hypnotic activity were then investigated using hole cross, open field, hole
      board, rota-rod, and thiopental sodium-induced sleeping time determination tests
      in mice at the doses of 50, 100, and 200 mg/kg of EESD. Diazepam at the dose of 1
      mg/kg was used as a reference drug in all the experiments. We found that EESD
      produced a significant dose-dependent inhibition of locomotor activity of mice
      both in hole cross and open field tests (P < 0.05). Besides, it also decreased
      rota-rod performances and the number of head dips in hole-board test.
      Furthermore, EESD significantly decreased the induction time to sleep and
      prolonged the duration of sleeping, induced by thiopental sodium. Taken together,
      our study suggests that EESD may possess sedative principles with potent hypnotic
      properties. 

PMID- 25861373
TI  - Clinical effects of thai herbal compress: a systematic review and meta-analysis.
AB  - Objective. To determine the clinical effects of Thai herbal compress. Methods.
      International and Thai databases were searched from inception through September
      2014. Comparative clinical studies investigating herbal compress for any
      indications were included. Outcomes of interest included level of pain,
      difficulties in performing activities, and time from delivery to milk secretion.
      Mean changes of the outcomes from baseline were compared between herbal compress
      and comparators by calculating mean difference. Results. A total of 13 studies
      which involved 778 patients were selected from 369 articles identified. The
      overall effects of Thai herbal compress on reducing osteoarthritis (OA) and
      muscle pain were not different from those of nonsteroidal anti-inflammatory
      drugs, knee exercise, and hot compress. However, the reduction of OA pain in the
      herbal compress group tended to be higher than that of any comparators (weighted
      mean difference 0.419; 95% CI -0.004, 0.842) with moderate heterogeneity (I (2) =
      58.3%, P = 0.048). When compared with usual care, herbal compress provided
      significantly less time from delivery to milk secretion in postpartum mothers
      (mean difference -394.425 minutes; 95% CI -620.084, -168.766). Conclusion. Thai
      herbal compress may be considered as an alternative for osteoarthritis and muscle
      pain and could also be used as a treatment of choice to induce lactation. 

PMID- 25861374
TI  - Mutations in the PCNA-binding site of CDKN1C inhibit cell proliferation by
      impairing the entry into S phase.
AB  - CDKN1C (also known as P57 (kip2) ) is a cyclin-dependent kinase inhibitor that
      functions as a negative regulator of cell proliferation through G1 phase cell
      cycle arrest. Recently, our group described gain-of-function mutations in the
      PCNA-binding site of CDKN1C that result in an undergrowth syndrome called IMAGe
      Syndrome (Intrauterine Growth Restriction, Metaphyseal dysplasia, Adrenal
      hypoplasia, and Genital anomalies), with life-threatening consequences. Loss-of
      function mutations in CDKN1C have been identified in 5-10% of individuals with
      Beckwith-Wiedemann syndrome (BWS), an overgrowth disorder with features that are
      the opposite of IMAGe syndrome. Here, we investigate the effects of IMAGe
      associated mutations on protein stability, cell cycle progression and cell
      proliferation. Mutations in the PCNA-binding site of CDKN1C significantly
      increase CDKN1C protein stability and prevent cell cycle progression into the S
      phase. Overexpression of either wild-type or BWS-mutant CDKN1C inhibited cell
      proliferation. However, the IMAGe-mutant CDKN1C protein decreased cell growth
      significantly more than both the wild-type or BWS protein. These findings bring
      new insights into the molecular events underlying IMAGe syndrome. 

PMID- 25861371
TI  - Establishment of a comprehensive list of candidate antiaging medicinal herb used
      in korean medicine by text mining of the classical korean medical literature,
      "dongeuibogam," and preliminary evaluation of the antiaging effects of these
      herbs.
AB  - The major objectives of this study were to provide a list of candidate antiaging
      medicinal herbs that have been widely utilized in Korean medicine and to organize
      preliminary data for the benefit of experimental and clinical researchers to
      develop new drug therapies by analyzing previous studies. "Dongeuibogam," a
      representative source of the Korean medicine literature, was selected to
      investigate candidate antiaging medicinal herbs and to identify appropriate terms
      that describe the specific antiaging effects that these herbs are predicted to
      elicit. In addition, we aimed to review previous studies that referenced the
      selected candidate antiaging medicinal herbs. From our chosen source,
      "Dongeuibogam," we were able to screen 102 terms describing antiaging effects,
      which were further classified into 11 subtypes. Ninety-seven candidate antiaging
      medicinal herbs were selected using the criterion that their antiaging effects
      were described using the same terms as those employed in "Dongeuibogam." These
      candidates were classified into 11 subtypes. Of the 97 candidate antiaging
      medicinal herbs selected, 47 are widely used by Korean medical doctors in Korea
      and were selected for further analysis of their antiaging effects. Overall, we
      found an average of 7.7 previous studies per candidate herb that described their
      antiaging effects. 

PMID- 25861375
TI  - Chagas parasite detection in blood images using AdaBoost.
AB  - The Chagas disease is a potentially life-threatening illness caused by the
      protozoan parasite, Trypanosoma cruzi. Visual detection of such parasite through
      microscopic inspection is a tedious and time-consuming task. In this paper, we
      provide an AdaBoost learning solution to the task of Chagas parasite detection in
      blood images. We give details of the algorithm and our experimental setup. With
      this method, we get 100% and 93.25% of sensitivity and specificity, respectively.
      A ROC comparison with the method most commonly used for the detection of malaria
      parasites based on support vector machines (SVM) is also provided. Our
      experimental work shows mainly two things: (1) Chagas parasites can be detected
      automatically using machine learning methods with high accuracy and (2) AdaBoost
      + SVM provides better overall detection performance than AdaBoost or SVMs alone.
      Such results are the best ones known so far for the problem of automatic
      detection of Chagas parasites through the use of machine learning, computer
      vision, and image processing methods.

PMID- 25861376
TI  - Molecular docking of potential inhibitors for influenza H7N9.
AB  - As a new strain of virus emerged in 2013, avian influenza A (H7N9) virus is a
      threat to the public health, due to its high lethality and pathogenicity.
      Furthermore, H7N9 has already generated various mutations such as neuraminidase
      R294K mutation which could make the anti-influenza oseltamivir less effective or
      ineffective. In this regard, it is urgent to develop new effective anti-H7N9
      drug. In this study, we used the general H7N9 neuraminidase and oseltamivir
      resistant influenza virus neuraminidase as the acceptors and employed the small
      molecules including quercetin, chlorogenic acid, baicalein, and oleanolic acid as
      the donors to perform the molecular docking for exploring the binding abilities
      between these small molecules and neuraminidase. The results showed that
      quercetin, chlorogenic acid, oleanolic acid, and baicalein present oseltamivir
      comparable high binding potentials with neuraminidase. Further analyses showed
      that R294K mutation in neuraminidase could remarkably decrease the binding
      energies for oseltamivir, while other small molecules showed stable binding
      abilities with mutated neuraminidase. Taken together, the molecular docking
      studies identified four potential inhibitors for neuraminidase of H7N9, which
      might be effective for the drug-resistant mutants.

PMID- 25861377
TI  - Feature engineering for drug name recognition in biomedical texts: feature
      conjunction and feature selection.
AB  - Drug name recognition (DNR) is a critical step for drug information extraction.
      Machine learning-based methods have been widely used for DNR with various types
      of features such as part-of-speech, word shape, and dictionary feature. Features
      used in current machine learning-based methods are usually singleton features
      which may be due to explosive features and a large number of noisy features when
      singleton features are combined into conjunction features. However, singleton
      features that can only capture one linguistic characteristic of a word are not
      sufficient to describe the information for DNR when multiple characteristics
      should be considered. In this study, we explore feature conjunction and feature
      selection for DNR, which have never been reported. We intuitively select 8 types
      of singleton features and combine them into conjunction features in two ways.
      Then, Chi-square, mutual information, and information gain are used to mine
      effective features. Experimental results show that feature conjunction and
      feature selection can improve the performance of the DNR system with a moderate
      number of features and our DNR system significantly outperforms the best system
      in the DDIExtraction 2013 challenge. 

PMID- 25861378
TI  - Global dynamics of avian influenza epidemic models with psychological effect.
AB  - Cross-sectional surveys conducted in Thailand and China after the outbreaks of
      the avian influenza A H5N1 and H7N9 viruses show a high degree of awareness of
      human avian influenza in both urban and rural populations, a higher level of
      proper hygienic practice among urban residents, and in particular a dramatically
      reduced number of visits to live markets in urban population after the influenza
      A H7N9 outbreak in China in 2013. In this paper, taking into account the
      psychological effect toward avian influenza in the human population, a bird-to
      human transmission model in which the avian population exhibits saturation effect
      is constructed. The dynamical behavior of the model is studied by using the basic
      reproduction number. The results demonstrate that the saturation effect within
      avian population and the psychological effect in human population cannot change
      the stability of equilibria but can affect the number of infected humans if the
      disease is prevalent. Numerical simulations are given to support the theoretical
      results and sensitivity analyses of the basic reproduction number in terms of
      model parameters that are performed to seek for effective control measures for
      avian influenza. 

PMID- 25861379
TI  - Access to mental health and psychosocial services in Cambodia by survivors of
      trafficking and exploitation: a qualitative study.
AB  - BACKGROUND: Emerging evidence indicates the extreme forms of violence and acute
      and longer-term mental health consequences associated with trafficking and
      exploitation. However, there has been little research on post-trafficking mental
      health and psychosocial support services for survivors. This study explored the
      availability and accessibility of mental health and psychosocial support services
      in Cambodia for women, men and children trafficked and exploited for sex or
      labour purposes. METHODS: Semi-structured interviews were conducted with a
      purposively selected sample of representatives from seven service organizations
      providing mental health and psychosocial support services for people who have
      been trafficked. This qualitative method was selected to gain insights into the
      service approaches and challenges faced by the small number of post-trafficking
      service providers in Cambodia. A conceptual framework outlining access dimensions
      associated with service provision guided the structure of the study. RESULTS:
      Findings indicate that among the available post-trafficking services, there are
      few trained mental health specialists, an over-representation of shelter services
      in urban versus rural areas and limited services for males, people with
      disabilities, individuals exploited for labour (versus sexual exploitation) and
      those with more serious mental illnesses. Providers believe that discrimination
      and stigma related to both mental health and human trafficking hinder trafficked
      people's willingness to access services, but suggest that awareness-raising may
      reduce these prejudices. Care in this sector is precarious due to over-reliance
      on financial support by donors versus government. Recent increases in newly
      qualified professionals and providers suggest potential improvements in the
      quality and availability of psychological support for trafficking survivors.
      CONCLUSIONS: Psychological support for the growing number of identified
      trafficking survivors in Cambodia will depend on improved geographical
      distribution of services, more mental health support professionals and growing
      acceptability of mental health service use among trafficked people and the
      Cambodian public.

PMID- 25861380
TI  - Fighting microbial drug resistance: a primer on the role of evolutionary biology
      in public health.
AB  - Although microbes have been evolving resistance to antimicrobials for millennia,
      the spread of resistance in pathogen populations calls for the development of new
      drugs and treatment strategies. We propose that successful, long-term resistance
      management requires a better understanding of how resistance evolves in the first
      place. This is an opportunity for evolutionary biologists to engage in public
      health, a collaboration that has substantial precedent. Resistance evolution has
      been an important tool for developing and testing evolutionary theory, especially
      theory related to the genetic basis of new traits and constraints on adaptation.
      The present era is no exception. The articles in this issue highlight the breadth
      of current research on resistance evolution and also its challenges. In this
      introduction, we review the conceptual advances that have been achieved from
      studying resistance evolution and describe a path forward. 

PMID- 25861382
TI  - Antibiotics in agriculture and the risk to human health: how worried should we
      be?
AB  - The use of antibiotics in agriculture is routinely described as a major
      contributor to the clinical problem of resistant disease in human medicine. While
      a link is plausible, there are no data conclusively showing the magnitude of the
      threat emerging from agriculture. Here, we define the potential mechanisms by
      which agricultural antibiotic use could lead to human disease and use case
      studies to critically assess the potential risk from each. The three mechanisms
      considered are as follows 1: direct infection with resistant bacteria from an
      animal source, 2: breaches in the species barrier followed by sustained
      transmission in humans of resistant strains arising in livestock, and 3: transfer
      of resistance genes from agriculture into human pathogens. Of these, mechanism 1
      is the most readily estimated, while significant is small in comparison with the
      overall burden of resistant disease. Several cases of mechanism 2 are known, and
      we discuss the likely livestock origins of resistant clones of Staphylococcus
      aureus and Enterococcus faecium, but while it is easy to show relatedness the
      direction of transmission is hard to assess in robust fashion. More difficult yet
      to study is the contribution of mechanism 3, which may be the most important of
      all. 

PMID- 25861383
TI  - Role of pleiotropy during adaptation of TEM-1 beta-lactamase to two novel
      antibiotics.
AB  - Pleiotropy is a key feature of the genotype-phenotype map, and its form and
      extent have many evolutionary implications, including for the dynamics of
      adaptation and the evolution of specialization. Similarly, pleiotropic effects of
      antibiotic resistance mutations may affect the evolution of antibiotic resistance
      in the simultaneous or fluctuating presence of different antibiotics. Here, we
      study the role of pleiotropy during the in vitro adaptation of the enzyme TEM-1
      beta-lactamase to two novel antibiotics, cefotaxime (CTX) and ceftazidime (CAZ).
      We subject replicate lines for four rounds of evolution to selection with CTX and
      CAZ alone, and in their combined and fluctuating presence. Evolved alleles show
      positive correlated responses when selecting with single antibiotics.
      Nevertheless, pleiotropic constraints are apparent from the effects of single
      mutations and from selected alleles showing smaller correlated than direct
      responses and smaller responses after simultaneous and fluctuating selection with
      both than with single antibiotics. We speculate that these constraints result
      from structural changes in the oxyanion pocket surrounding the active site, where
      accommodation of CTX and the larger CAZ is balanced against their positioning
      with respect to the active site. Our findings suggest limited benefits from the
      combined or fluctuating application of these related cephalosporins for
      containing antibiotic resistance. 

PMID- 25861381
TI  - Public health evolutionary biology of antimicrobial resistance: priorities for
      intervention.
AB  - The three main processes shaping the evolutionary ecology of antibiotic
      resistance (AbR) involve the emergence, invasion and occupation by antibiotic
      resistant genes of significant environments for human health. The process of
      emergence in complex bacterial populations is a high-frequency, continuous
      swarming of ephemeral combinatory genetic and epigenetic explorations inside
      cells and among cells, populations and communities, expanding in different
      environments (migration), creating the stochastic variation required for
      evolutionary progress. Invasion refers to the process by which AbR significantly
      increases in frequency in a given (invaded) environment, led by external invaders
      local multiplication and spread, or by endogenous conversion. Conversion occurs
      because of the spread of AbR genes from an exogenous resistant clone into an
      established (endogenous) bacterial clone(s) colonizing the environment; and/or
      because of dissemination of particular resistant genetic variants that emerged
      within an endogenous clonal population. Occupation of a given environment by a
      resistant variant means a permanent establishment of this organism in this
      environment, even in the absence of antibiotic selection. Specific interventions
      on emergence influence invasion, those acting on invasion also influence
      occupation and interventions on occupation determine emergence. Such
      interventions should be simultaneously applied, as they are not simple solutions
      to the complex problem of AbR. 

PMID- 25861384
TI  - Costs of antibiotic resistance - separating trait effects and selective effects.
AB  - Antibiotic resistance can impair bacterial growth or competitive ability in the
      absence of antibiotics, frequently referred to as a 'cost' of resistance. Theory
      and experiments emphasize the importance of such effects for the distribution of
      resistance in pathogenic populations. However, recent work shows that costs of
      resistance are highly variable depending on environmental factors such as
      nutrient supply and population structure, as well as genetic factors including
      the mechanism of resistance and genetic background. Here, we suggest that such
      variation can be better understood by distinguishing between the effects of
      resistance mechanisms on individual traits such as growth rate or yield ('trait
      effects') and effects on genotype frequencies over time ('selective effects'). We
      first give a brief overview of the biological basis of costs of resistance and
      how trait effects may translate to selective effects in different environmental
      conditions. We then review empirical evidence of genetic and environmental
      variation of both types of effects and how such variation may be understood by
      combining molecular microbiological information with concepts from evolution and
      ecology. Ultimately, disentangling different types of costs may permit the
      identification of interventions that maximize the cost of resistance and
      therefore accelerate its decline. 

PMID- 25861385
TI  - The fitness costs of antibiotic resistance mutations.
AB  - Antibiotic resistance is increasing in pathogenic microbial populations and is
      thus a major threat to public health. The fate of a resistance mutation in
      pathogen populations is determined in part by its fitness. Mutations that suffer
      little or no fitness cost are more likely to persist in the absence of antibiotic
      treatment. In this review, we performed a meta-analysis to investigate the
      fitness costs associated with single mutational events that confer resistance.
      Generally, these mutations were costly, although several drug classes and species
      of bacteria on average did not show a cost. Further investigations into the rate
      and fitness values of compensatory mutations that alleviate the costs of
      resistance will help us to better understand both the emergence and management of
      antibiotic resistance in clinical settings. 

PMID- 25861386
TI  - The genetic basis of the fitness costs of antimicrobial resistance: a meta
      analysis approach.
AB  - The evolution of antibiotic resistance carries a fitness cost, expressed in terms
      of reduced competitive ability in the absence of antibiotics. This cost plays a
      key role in the dynamics of resistance by generating selection against resistance
      when bacteria encounter an antibiotic-free environment. Previous work has shown
      that the cost of resistance is highly variable, but the underlying causes remain
      poorly understood. Here, we use a meta-analysis of the published resistance
      literature to determine how the genetic basis of resistance influences its cost.
      We find that on average chromosomal resistance mutations carry a larger cost than
      acquiring resistance via a plasmid. This may explain why resistance often evolves
      by plasmid acquisition. Second, we find that the cost of plasmid acquisition
      increases with the breadth of its resistance range. This suggests a potentially
      important limit on the evolution of extensive multidrug resistance via plasmids.
      We also find that epistasis can significantly alter the cost of mutational
      resistance. Overall, our study shows that the cost of antimicrobial resistance
      can be partially explained by its genetic basis. It also highlights both the
      danger associated with plasmidborne resistance and the need to understand why
      resistance plasmids carry a relatively low cost. 

PMID- 25861387
TI  - Understanding genetic variation in in vivo tolerance to artesunate: implications
      for treatment efficacy and resistance monitoring.
AB  - Artemisinin-based drugs are the front-line weapon in the treatment of human
      malaria cases, but there is concern that recent reports of slow clearing
      infections may signal developing resistance to treatment. In the absence of
      molecular markers for resistance, current efforts to monitor drug efficacy are
      based on the rate at which parasites are cleared from infections. However, some
      knowledge of the standing variation in parasite susceptibility is needed to
      identify a meaningful increase in infection half-life. Here, we show that five
      previously unexposed genotypes of the rodent malaria parasite Plasmodium chabaudi
      differ substantially in their in vivo response to treatment. Slower clearance
      rates were not linked to parasite virulence or growth rate, going against the
      suggestion that drug treatment will drive the evolution of virulence in this
      system. The level of variation observed here in a relatively small number of
      genotypes suggests existing 'resistant' parasites could be present in the
      population and therefore, increased parasite clearance rates could represent
      selection on pre-existing variation rather than de novo resistance events. This
      has implications for resistance monitoring as susceptibility may depend on
      evolved traits unrelated to drug exposure. 

PMID- 25861389
TI  - Identification of furfural resistant strains of Saccharomyces cerevisiae and
      Saccharomyces paradoxus from a collection of environmental and industrial
      isolates.
AB  - BACKGROUND: Fermentation of bioethanol using lignocellulosic biomass as a raw
      material provides a sustainable alternative to current biofuel production methods
      by utilising waste food streams as raw material. Before lignocellulose can be
      fermented, it requires physical, chemical and enzymatic treatment in order to
      release monosaccharides, a process that causes the chemical transformation of
      glucose and xylose into the cyclic aldehydes furfural and hydroxyfurfural. These
      furan compounds are potent inhibitors of Saccharomyces fermentation, and
      consequently furfural tolerant strains of Saccharomyces are required for
      lignocellulosic fermentation. RESULTS: This study investigated yeast tolerance to
      furfural and hydroxyfurfural using a collection of 71 environmental and
      industrial isolates of the baker's yeast Saccharomyces cerevisiae and its closest
      relative Saccharomyces paradoxus. The Saccharomyces strains were initially
      screened for growth on media containing 100 mM glucose and 1.5 mg ml(-1)
      furfural. Five strains were identified that showed a significant tolerance to
      growth in the presence of furfural, and these were then screened for growth and
      ethanol production in the presence of increasing amounts (0.1 to 4 mg ml(-1)) of
      furfural. CONCLUSIONS: Of the five furfural tolerant strains, S. cerevisiae
      National Collection of Yeast Cultures (NCYC) 3451 displayed the greatest furfural
      resistance and was able to grow in the presence of up to 3.0 mg ml(-1) furfural.
      Furthermore, ethanol production in this strain did not appear to be inhibited by
      furfural, with the highest ethanol yield observed at 3.0 mg ml(-1) furfural.
      Although furfural resistance was not found to be a trait specific to any one
      particular lineage or population, three of the strains were isolated from
      environments where they might be continually exposed to low levels of furfural
      through the ongoing natural degradation of lignocelluloses, and would therefore
      develop elevated levels of resistance to these furan compounds. Thus, these
      strains represent good candidates for future studies of genetic variation
      relevant to understanding and manipulating furfural resistance and in the
      development of tolerant ethanologenic yeast strains for use in bioethanol
      production from lignocellulose processing.

PMID- 25861390
TI  - The difference in effective light penetration may explain the superiority in
      photosynthetic efficiency of attached cultivation over the conventional open pond
      for microalgae.
AB  - BACKGROUND: The 'attached cultivation' technique for microalgae production,
      combining the immobilized biofilm technology with proper light dilution
      strategies, has shown improved biomass production and photosynthetic efficiency
      over conventional open-pond suspended cultures. However, how light is transferred
      and distributed inside the biofilm has not been clearly defined yet. RESULTS: In
      this research, the growth, photosynthetic oxygen evolution, and specific growth
      rate for microalgal cells in both open-pond and attached cultivation were studied
      to determine the effective light penetration at different phases of the
      cultivation. As a result, the light conditions inside the culture broth as well
      as the biofilm were revealed for the first time. Results showed that outdoor, in
      a conventional 20-cm deep open pond, all of the algal cells were fully
      illuminated in the first 3 days of cultivation. As the biomass concentration
      increased from day 4 to day 10, the light could only effectively penetrate 45.5%
      of the open-pond depth, and then effective light penetration gradually decreased
      to 31.1% at day 31, when the biomass density reached a maximum value of 0.45 g L(
      1) or 90 g m(-2). In the attached cultivation system, under nitrogen-replete
      condition, almost 100% of the immobilized algal cells inside the biofilm were
      effectively illuminated from day 0 through day 10 when the biomass density
      increased from 8.8 g m(-2) to 107.6 g m(-2). CONCLUSION: Higher light penetration
      efficiency might be the reason why, using attached cultivation, observed values
      for photosynthetic efficiency were higher than those recorded in conventional
      open-pond suspended cultures.

PMID- 25861391
TI  - Genome sequencing of Clostridium butyricum DKU-01, isolated from infant feces.
AB  - BACKGROUND: Clostridium butyricum is a butyric acid-producing anaerobic
      bacteriuma, and commonly present as gut microbiota in humans. This species has
      been used as a probiotic for the prevention of diarrhea in humans. In this study,
      we report the draft genome of C. butyricum DKU-01, which was isolated from infant
      feces, to better understand the characteristics of this strain so that it can
      later be used in the development of probiotic products. RESULTS: A total of 79
      contigs generated by hybrid assembly of sequences obtained from Roche 454 and
      Illumina Miseq sequencing systems were investigated. The assembled genome of
      strain DKU-01 consisted of 4,519,722 bp (28.62% G + C content) with a N50 contig
      length of 108,221 bp and 4,037 predicted CDSs. The extracted 16S rRNA gene from
      genome sequences of DKU-01 was similar to Clostridium butyricum with 99.63%
      pairwise similarity. The sequence of strain DKU-01 was compared with previously
      reported genome sequences of C. butyricum. The value of average nucleotide
      identity between strains DKU-01 and C. butyricum 60E3 was 98.74%, making it the
      most similar strain to DKU-01. CONCLUSIONS: We sequenced the DKU-01 strain
      isolated from infant feces, and compared it with the available genomes of C.
      butyricum on a public database. Genes related to Fructooligosaccharide
      utilization were detected in the genome of strain DKU-01 and compared with other
      genera, such as Bifidobacterium and Streptococcus. We found that strain DKU-01
      can metabolize a wide range of carbohydrates in comparative genome result.
      Further analyses of the comparative genome and fermentation study can provide the
      information necessary for the development of strain DKU-01 for probiotics.

PMID- 25861392
TI  - Multiplex bisulfite PCR resequencing of clinical FFPE DNA.
AB  - BACKGROUND: The clinical utility of DNA methylation as a predictive or prognostic
      biomarker requires scalable resequencing protocols for bisulfite-converted DNA.
      Key features of any validation method should be adaptability for low- or high
      throughput needs and high reproducibility, and should only require minimal
      amounts of precious clinical sample as input material. Critically, this method
      should also deliver robust results when working with bisulfite-converted DNA
      extracted from formalin-fixed, paraffin-embedded (FFPE) blocks. RESULTS: We
      report here for the first time on comparison studies between the Fluidigm Access
      Array system and multiplex assays for multiplex bisulfite PCR resequencing. The
      requirement of the Fluidigm Access Array system for high template amounts and its
      sensitivity to variations in template quality rendered it unsuitable for
      bisulfite PCR applications utilizing FFPE DNA. In response to this limitation, we
      established a multiplex bisulfite PCR assay capable of delivering robust
      methylation data using minimal amounts of FFPE clinical DNA. To evaluate the
      parameters and reproducibility of this assay, 57 amplicons were used to prepare
      sequencing libraries in triplicate for 13 FFPE tumour samples, as well as a
      series of 5 methylated controls (0%, 25%, 50%, 75%, and 100%). Analysis of this
      data demonstrated that this multiplex assay had high reproducibility (mean
      standard deviation of 1.4% for methylation values), was low cost, required low
      sample input (50 ng of DNA or less), and could be scaled for both low- and high
      throughput needs. Notably, ExoSAP-IT (exonuclease I) treatment to remove residual
      primers in bisulfite resequencing libraries appeared to degrade the library and
      generate a high-molecular weight smear which may impact on the degree of
      methylation assessed. CONCLUSIONS: Multiplex bisulfite PCR assays represent a
      convenient and scalable method for validation and screening of methylated DNA
      regions from archival FFPE DNA. Moreover, the library construction process
      detailed here can be rapidly optimized and implemented with a minimal amount of
      work, can be performed using the standard equipment found in any molecular
      biology laboratory, and can be easily adapted for use on both genomic DNA and
      bisulfite DNA applications. However, in preparing bisulfite libraries for
      sequencing, the use of ExoSAP-IT is not recommended due to potential off-target
      nuclease effects which may impact downstream methylation analysis.

PMID- 25861394
TI  - Acute granulomatous iridocyclitis in a child with tubulointerstitial nephritis
      and uveitis syndrome.
AB  - BACKGROUND: Tubulointerstitial nephritis and uveitis [TINU] syndrome is a rare
      disorder that may also be underdiagnosed. Patients with TINU syndrome typically
      present with an acute bilateral nongranulomatous anterior uveitis following
      symptoms of systemic illness. FINDINGS: We report the case of a 15-year-old girl
      who presented with acute granulomatous iridocyclitis and was diagnosed with TINU
      syndrome based on renal biopsy findings. Both her uveitis and interstitial
      nephritis promptly responded to high-dose corticosteroid treatment, and there
      were no relapses during follow-up of 20 months. CONCLUSIONS: TINU should be
      included in the differential diagnosis of patients who present with acute
      granulomatous uveitis.

PMID- 25861395
TI  - Bilateral choroidal tuberculoma in miliary tuberculosis - report of a case.
AB  - BACKGROUND: A choroidal mass or granuloma is a feature of ocular tuberculosis
      (TB). Tubercles can arise in the early stages of progression of TB and indicate
      hematogenous dissemination before the development of symptomatic disease.
      Tubercular subretinal granuloma is responsive to treatment with anti-tuberculosis
      therapy, and prompt treatment helps resolve the lesion completely. FINDINGS: We
      report a case of a solitary large active choroidal tuberculoma in one eye and
      multiple healed tubercles in the other. The patient was an immunocompetent girl
      with splenic and miliary TB and had a relatively asymptomatic systemic status.
      Aqueous humor analysis by polymerase chain reaction (PCR) and real-time PCR (RT
      PCR) was negative for the Mycobacterium tuberculosis genome. Based on clinical
      history and investigations, treatment with four-drug regimen of anti-tubercular
      treatment with concomitant corticosteroids was started, and total healing of the
      lesion occurred in 3 months. CONCLUSIONS: This case highlights the fact that in
      some patients, analysis of the aqueous may not provide any clue to the
      confirmation of an active tubercular choroidal granuloma and an association
      between splenic tuberculosis and choroidal tubercles has never been reported in
      the past.

PMID- 25861396
TI  - Uveitic crystalline maculopathy.
AB  - BACKGROUND: The purpose of this case report is to present a novel cause of
      crystalline maculopathy. FINDINGS: A 52-year-old Japanese female presented with a
      4-month history of decreased vision in the left eye. Best corrected visual acuity
      in the left eye was 20/40. Dilated fundus examination of the right eye was
      unremarkable, but that of the left eye demonstrated foveal yellow-green
      intraretinal crystals and mild vitritis. Optical coherence tomography of the left
      eye revealed small intraretinal fluid cysts and intraretinal crystals. Ultra
      widefield fluorescein angiography was normal in the right eye, but that of the
      left eye demonstrated features of intermediate uveitis. There was no history or
      findings to suggest any cause for the crystals other than the uveitis.
      CONCLUSIONS: We propose that this may represent a novel category of crystalline
      retinopathy, termed uveitic crystalline maculopathy. We hypothesize that
      breakdown of the blood-retinal barrier as seen in uveitis may contribute to the
      deposition of crystals in the macula, although the precise composition of the
      crystals is unknown.

PMID- 25861397
TI  - Long-term follow-up of herpetic non-necrotizing retinopathy with occlusive
      retinal vasculitis and neovascularization.
AB  - BACKGROUND: Herpetic necrotizing retinitis is a well-recognized entity. A few
      cases of herpetic non-necrotizing retinitis were previously reported. FINDINGS:
      We retrospectively report two cases of herpetic non-necrotizing retinopathy with
      a long follow-up. A 19-year-old woman presented with a bilateral diffuse
      occlusive retinal vasculitis, peripheral neovascularization, and no signs of
      retinal necrosis. Long-lasting immunosuppressive treatment failed to control the
      vasculitis until herpes simplex virus type 1 (HSV1) was demonstrated by
      polymerase chain reaction (PCR) in the aqueous. Acyclovir was then added and
      immunosuppressive tapered and eventually stopped resulting in a resolution of
      vasculitis. Only two relapses occurred during the next 6 years and responded
      rapidly to oral acyclovir. An 11-year-old boy presented with unilateral scar of
      stromal keratitis, severe vitritis, and optic disc neovascularization, followed 6
      weeks later by peripheral occlusive retinal vasculitis. Therapeutic and
      diagnostic vitrectomy was performed, and PCR was found to be positive for
      varicella zoster virus (VZV) in a vitreous specimen. The inflammation responded
      to oral acyclovir therapy. Recurrence of anterior uveitis with iris
      depigmentation occurred 4 months after treatment was arrested. After 4 years, he
      presented again with a recurrence of anterior inflammation and cystoid macular
      edema (CME). No sign of inflammation was seen for the next 10 years. CONCLUSIONS:
      These rare cases support the possible role of herpes viruses (HSV or VZV) in
      occlusive vasculitis without retinal necrosis. PCR was useful to raise the
      diagnosis and to adapt the treatment. A good response was obtained on oral
      antiviral therapy.

PMID- 25861398
TI  - Birdshot chorioretinopathy in a male patient with facioscapulohumeral muscular
      dystrophy.
AB  - We report a case of birdshot chorioretinopathy (BSCR) in a patient with
      facioscapulohumeral muscular dystrophy (FSHD). A 40-year-old male with history of
      facioscapulohumeral muscular dystrophy with significant facial diplegia and
      lagophthalmos presents for an evaluation of bilateral choroiditis with vasculitis
      and optic disc edema. Clinical examination included fundus and autofluorescence
      photographs, fluorescein angiography, and optical coherence tomography. To our
      knowledge, this patient represents the first reported case of birdshot
      chorioretinopathy with facioscapulohumeral muscular dystrophy. Patients with FSHD
      can present with ocular findings and should be screened with dilated fundus
      examinations for retinal vascular changes and posterior uveitis. 

PMID- 25861399
TI  - Nodular syphilitic scleritis masquerading as an ocular tumor.
AB  - BACKGROUND: Scleritis may be the initial or only presenting feature of systemic,
      autoimmune, or infectious disorders. Corticosteroids are the mainstay of
      treatment for immune-mediated scleritis. However, steroids could prove
      detrimental when used to treat infectious scleritis. Hence, infectious causes of
      scleritis should be ruled out. FINDINGS: A 47-year-old male from central India
      presented with swelling, pain, and redness in the left eye since 2 months. The
      patient was diagnosed elsewhere as having an extraocular extension of intraocular
      tumor and advised radiation brachytherapy for the same. Clinical examination
      revealed nodular scleritis in the left eye. The patient did not have any systemic
      illness or complaints suggestive of connective tissue disease. Laboratory
      investigations ruled out the same. However, Venereal Disease Research Laboratory
      (VDRL) test was positive. Rapid plasma reagin (RPR) test and Treponema pallidum
      hemagglutination assay (TPHA) were also positive, confirming the diagnosis of
      syphilis. Ultrabiomicroscopy (UBM) and ultrasound scan of the eye ruled out
      intraocular tumor. Treatment was initiated with benzathine penicillin 2.4 million
      units per week for 3 weeks to which the patient responded remarkably well.
      CONCLUSIONS: Although rare, syphilis can present as nodular scleritis
      masquerading as ocular tumor. Syphilis must be considered in the list of
      etiological diagnoses in patients presenting with nodular scleritis, and testing
      for this disease should be a part of routine investigation in patients with
      scleritis.

PMID- 25861400
TI  - Pink hypopyon in a patient with Serratia marcescens corneal ulceration.
AB  - A 65-year-old woman presented to the emergency ward at the Massachusetts Eye and
      Ear Infirmary with 2 days of redness, irritation, photophobia, and diminished
      vision in her left eye. She was found to have a large central corneal ulcer with
      a small hypopyon. On the following day, after initiation of broad-spectrum
      antibiotics, the patient had improved symptoms but now had a 2-mm hypopyon that
      was distinctly pink in color. Cultures were positive for Serratia marcescens. A
      pink hypopyon, a rare occurrence, alerted the authors to a causative agent of
      Enterobacteriacae, either Klebsiella or Serratia. Immediate and intensive
      treatment was subsequently initiated. 

PMID- 25861393
TI  - From inflammaging to healthy aging by dietary lifestyle choices: is epigenetics
      the key to personalized nutrition?
AB  - The progressively older population in developed countries is reflected in an
      increase in the number of people suffering from age-related chronic inflammatory
      diseases such as metabolic syndrome, diabetes, heart and lung diseases, cancer,
      osteoporosis, arthritis, and dementia. The heterogeneity in biological aging,
      chronological age, and aging-associated disorders in humans have been ascribed to
      different genetic and environmental factors (i.e., diet, pollution, stress) that
      are closely linked to socioeconomic factors. The common denominator of these
      factors is the inflammatory response. Chronic low-grade systemic inflammation
      during physiological aging and immunosenescence are intertwined in the
      pathogenesis of premature aging also defined as 'inflammaging.' The latter has
      been associated with frailty, morbidity, and mortality in elderly subjects.
      However, it is unknown to what extent inflammaging or longevity is controlled by
      epigenetic events in early life. Today, human diet is believed to have a major
      influence on both the development and prevention of age-related diseases. Most
      plant-derived dietary phytochemicals and macro- and micronutrients modulate
      oxidative stress and inflammatory signaling and regulate metabolic pathways and
      bioenergetics that can be translated into stable epigenetic patterns of gene
      expression. Therefore, diet interventions designed for healthy aging have become
      a hot topic in nutritional epigenomic research. Increasing evidence has revealed
      that complex interactions between food components and histone modifications, DNA
      methylation, non-coding RNA expression, and chromatin remodeling factors
      influence the inflammaging phenotype and as such may protect or predispose an
      individual to many age-related diseases. Remarkably, humans present a broad range
      of responses to similar dietary challenges due to both genetic and epigenetic
      modulations of the expression of target proteins and key genes involved in the
      metabolism and distribution of the dietary constituents. Here, we will summarize
      the epigenetic actions of dietary components, including phytochemicals, and macro
      and micronutrients as well as metabolites, that can attenuate inflammaging. We
      will discuss the challenges facing personalized nutrition to translate highly
      variable interindividual epigenetic diet responses to potential individual health
      benefits/risks related to aging disease. 

PMID- 25861401
TI  - In-bag dislocation of intraocular lens in patients with uveitis: a case series.
AB  - BACKGROUND: Improvement in surgical devices and intraocular lenses has made
      modern cataract surgery a safe procedure with decreasing complication rates.
      Intraocular lens dislocation is a serious complication after cataract surgery.
      Although most dislocations occur during the first week postoperative period, late
      intraocular lens dislocation occurring 3 months or later post-surgery has been
      reported with increasing frequency in recent years as a result of progressive
      zonular dehiscence. We report the clinical features, management and outcomes of
      five cases of late in-bag dislocation of intraocular lens in patients with
      underlying uveitis. This is a retrospective case series and literature review.
      RESULTS: We identified five eyes in five patients with uveitis and late in-bag
      intraocular lens dislocation. Two patients had multifocal choroiditis, two
      herpetic uveitis and retinitis and two Fuchs' heterochromic iridocyclitis in five
      patients. Mean age at the time of cataract surgery was 50. Best vision ranged
      from counting fingers to 6/18 preoperatively and ranged from 6/36 to 6/6
      postoperatively. All had right eye dislocation with mean time from initial
      cataract surgery to intraocular lens dislocation of 81 months. Explantation of
      dislocated intraocular lens and vitrectomy were performed in four cases; three
      had anterior chamber intraocular lens placement. One case was managed
      conservatively. Best vision ranged from light perception to 6/7.5 at time of
      dislocation and ranged from 6/36 to 6/6(-2) at follow-up. CONCLUSIONS: Late in
      bag dislocation intraocular lens can complicate cataract surgery in patients with
      underlying uveitis. This case series identified that the mean time to in-bag
      intraocular lens dislocation in five uveitis patients was 81 months after
      uncomplicated cataract surgery, comparable with the time reported in the
      available literature of patients with pseudoexfoliation syndrome. This series
      also found that lens explantation and replacement with anterior chamber
      intraocular lens achieved good outcomes. Further investigation is warranted to
      ascertain the strategies to identify patients at risk and to prevent and better
      manage intraocular lens dislocation in patients with uveitis.

PMID- 25861402
TI  - Stability analysis of memristor-based fractional-order neural networks with
      different memductance functions.
AB  - In this paper, the problem of the existence, uniqueness and uniform stability of
      memristor-based fractional-order neural networks (MFNNs) with two different types
      of memductance functions is extensively investigated. Moreover, we formulate the
      complex-valued memristor-based fractional-order neural networks (CVMFNNs) with
      two different types of memductance functions and analyze the existence,
      uniqueness and uniform stability of such networks. By using Banach contraction
      principle and analysis technique, some sufficient conditions are obtained to
      ensure the existence, uniqueness and uniform stability of the considered MFNNs
      and CVMFNNs with two different types of memductance functions. The analysis
      results establish from the theory of fractional-order differential equations with
      discontinuous right-hand sides. Finally, four numerical examples are presented to
      show the effectiveness of our theoretical results. 

PMID- 25861403
TI  - Use & Misuse of Water-filtered Tobacco Smoking Pipes in the World. Consequences
      for Public Health, Research & Research Ethics.
AB  - BACKGROUND: The traditional definition of an "epidemic" has been revisited by
      antismoking researchers. After 400 years, Doctors would have realized that one
      aspect of an ancient cultural daily practice of Asian and African societies was
      in fact a "global "epidemic"". This needed further investigation particularly if
      one keeps in his mind the health aspects surrounding barbecues. METHOD: Here, up
      to-date biomedical results are dialectically confronted with anthropological
      findings, hence in real life, in order to highlight the extent of the global
      confusion: from the new definition of an "epidemic" and "prevalence" to the myth
      of "nicotine "addiction"" and other themes in relation to water filtered tobacco
      smoking pipes (WFTSPs). RESULTS: We found that over the last decade, many
      publications, -particularly reviews, "meta-analyses" and "systematic reviews"- on
      (WFTSPs), have actually contributed to fuelling the greatest mix-up ever
      witnessed in biomedical research. One main reason for such a situation has been
      the absolute lack of critical analysis of the available literature and the
      uncritical use of citations (one seriously flawed review has been cited up to 200
      times). Another main reason has been to take as granted a biased smoking robot
      designed at the US American of Beirut whose measured yields of toxic chemicals
      may differ dozens of times from others' based on the same "protocol". We also
      found that, for more than one decade, two other main methodological problems are:
      1) the long-lived unwillingness to distinguish between use and misuse; 2) the
      consistent unethical rejection of biomedical negative results which,
      interestingly, are quantitatively and qualitatively much more instructive than
      the positive ones. CONCLUSION: the great majority of WFTSP toxicity studies have
      actually measured, voluntarily or not, their misuse aspects, not the use in
      itself. This is in contradiction with both the harm reduction and public health
      doctrines. The publication of negative results should be encouraged instead of
      being stifled.

PMID- 25861404
TI  - Total Hip Prostheses in Standing, Sitting and Squatting Positions: An Overview of
      Our 8 Years Practice Using the EOS Imaging Technology.
AB  - More total hip arthroplasty (THA) is performed worldwide and especially in
      younger and more active patients compared to earlier decades. One of the focuses
      of THA research in the future will be on optimizing the radiological follow-up of
      these patients using 2D and 3D measurements of implants position while reducing
      the radiation dose delivered. Low-dose EOS((r)) imaging is an innovative slot
      scanning radiograph system providing valuable information in patient functional
      positions (standing, sitting and even squatting positions). EOS has been proven
      accurate and reliable without significant inconvenience caused by the metallic
      artifacts of implants. The ability to obtain precise data on implant orientation
      according to the patient posture opens new perspectives for a comprehensive
      analysis of the pelvic frontal and sagittal balance and its potential impact on
      implants function and failures. We report our 8 years experience on our first 300
      THA patients using this technology routinely for pre and post op evaluation. Our
      results will be compared and confronted with the actual literature about this
      innovative technology. We shall especially emphasize our experience about
      patients with abnormal posture and the evolution of the subject over time,
      because the phenomenon of an aging spine is frequently associated with the
      process of aging hips. 

PMID- 25861405
TI  - Femoral component rotation in patellofemoral joint replacement: a study protocol
      for a prospective observational study.
AB  - Patellofemoral joint replacement is a successful treatment option for isolated
      patellofemoral osteoarthritis. The short and mid-term outcomes are related to
      malposition and unexplained pain. Whether external rotation of the femoral
      component in isolated patellofemoral joint replacement is required is unclear.
      The primary aim of this study is to determine the CT-measured femoral component
      rotation of patellofemoral joint replacement relative to the transepicondylar
      axis. The secondary aim is to correlate the CT-measured femoral component
      rotation with the clinical outcomes at 1-year follow-up as assessed with the KOOS
      questionnaire. We designed a prospective observational study with medical
      research ethics committee and institutional review board approval. A total of 40
      patients who will be treated with patellofemoral joint replacement for isolated
      patellofemoral osteoarthritis will be included. Intra-operatively, rotation of
      the femoral component will be assessed using anatomical landmarks including the
      epicondylar axis, Whiteside's line, and lower leg axis. The aim is to insert the
      femoral component between 3 and 6 degrees external rotation relative to the
      transepicondylar axis. Two experienced musculoskeletal radiologists will measure
      the angle between the transepicondylar axis and the femoral component, two to
      three days after surgery. The primary outcome is the CT-based femoral component
      rotation of the prosthesis relative to the transepicondylar axis. The secondary
      outcome is the patient reported KOOS questionnaire at 1-year follow-up.
      Successful completion of this study will provide data on the actual amount of
      femoral component rotation in patellofemoral joint replacement, and its
      relationship with clinical results. (Netherlands Trial Register NTR4175). 

PMID- 25861406
TI  - Test-retest reliability and convergent validity of a computer based hand function
      test protocol in people with arthritis.
AB  - OBJECTIVES: A computer based hand function assessment tool has been developed to
      provide a standardized method for quantifying task performance during
      manipulations of common objects/tools/utensils with diverse physical properties
      and grip/grasp requirements for handling. The study objectives were to determine
      test-retest reliability and convergent validity of the test protocol in people
      with arthritis. METHODS: Three different object manipulation tasks were evaluated
      twice in forty people with rheumatoid arthritis (RA) or hand osteoarthritis
      (HOA). Each object was instrumented with a motion sensor and moved in concert
      with a computer generated visual target. Self-reported joint pain and stiffness
      levels were recorded before and after each task. Task performance was determined
      by comparing the object movement with the computer target motion. This was
      correlated with grip strength, nine hole peg test, Disabilities of Arm, Shoulder,
      and Hand (DASH) questionnaire, and the Health Assessment Questionnaire (HAQ)
      scores. RESULTS: The test protocol indicated moderate to high test-retest
      reliability of performance measures for three manipulation tasks, intraclass
      correlation coefficients (ICCs) ranging between 0.5 to 0.84, p<0.05. Strength of
      association between task performance measures with self- reported
      activity/participation composite scores was low to moderate (Spearman rho <0.7).
      Low correlations (Spearman rho < 0.4) were observed between task performance
      measures and grip strength; and between three objects' performance measures.
      Significant reduction in pain and joint stiffness (p<0.05) was observed after
      performing each task. CONCLUSION: The study presents initial evidence on the test
      retest reliability and convergent validity of a computer based hand function
      assessment protocol in people with rheumatoid arthritis or hand osteoarthritis.
      The novel tool objectively measures overall task performance during a variety of
      object manipulation tasks done by tracking a computer based visual target. This
      allows an innovative method of assessing performance than considering the time
      taken to complete a task or relying on subjective measures of self-reports on a
      limited range of objects and tasks covered. In addition, joint pain and stiffness
      levels before and after a manipulation task are tracked, which is lacking in
      other hand outcome measures. Performance measures during a broad range of object
      manipulation tasks relate to many activities relevant to life role participation.
      Therefore, task performance evaluation of common objects, utensils, or tools
      would be more valuable to gauge the difficulties encountered in daily life by
      people with arthritis. Future studies should consider a few revisions of the
      present protocol and evaluate a number of different objects targeting strength,
      fine, and gross dexterity based tasks for a broader application of the tool in
      arthritis populations.

PMID- 25861407
TI  - The effect of obesity on theatre utilisation time during primary hip and knee
      replacements.
AB  - INTRODUCTION: The aim of this study is to assess the effect of body mass index
      (BMI) and body weight on theatre utilisation time during primary total hip (THR)
      and knee replacements (TKR). METHODS: A total of 1859 cases were included (820
      THR and 1039 TKR). Patients were divided into groups based on BMI and body
      weight. The time interval from 'starting anaesthesia' to 'transfer back to
      recovery' was used as total theatre time. Hierarchal regression analysis was then
      used to study the effect of BMI and body weight while controlling the effect of
      any confounding variables. RESULTS: In THR cases, the median theatre time was
      significantly different between BMI and body weight subgroups (p=0.001). In TKR
      cases, the median theatre time was more significantly different between weight
      subgroups (p<0.001) than BMI subgroups (p=0.021). Regression analysis showed that
      only weight remained a significant predictor (p=0.018) of theatre time in THR
      cases after controlling for other variables. In TKR cases, body weight and BMI
      were not predictors of theatre time after controlling for other variables.
      CONCLUSION: Body weight is a significant predictor of theatre time during THR.
      Neither weight nor BMI predicted theatre time during TKR.

PMID- 25861408
TI  - Minimally invasive percutaneous plate osteosynthesis does not increase
      complication rates in extra-articular distal tibial fractures.
AB  - BACKGROUND: Selection of a treatment method in cases of unstable, nonarticular
      distal tibial fractures is still a matter of discussion. Intramedullary nailing,
      which is a "gold standard" for tibial shaft fractures, does not always work for
      this specific transition area between diaphysis and metaphysis. Instead, new
      minimally invasive techniques with special implants are popular. AIMS: To
      determine the functional and radiological results of distal tibial fractures
      treated with minimally invasive percutaneous plate osteosynthesis (MIPPO)
      technique. STUDY DESIGN: Retrospective cohort analysis. METHODS: Thirty distal
      tibial fractures treated with MIPPO method, between January 2006 and December
      2010, were evaluated retrospectively. All patients were classified according to
      AO/OTA classification. Period of hospital stay, time of fracture union, time to
      allow full weight bearing, early and late complications were inquired. Functional
      outcomes were assessed by AOFAS scores. RESULTS: There were 13 male and 17 female
      patients with an average age of 44.26 (range, 22-77 years). One superficial
      infection and one malunion were observed. Two patients were revised for the loss
      of reduction and healed uneventfully. According to the AO/OTA classification, 23
      patients were 43-A1 (76.6%), 3 were 43-A2 (10%) and 4 were 43-A3 (13.3%). Post
      operative mean stay of patients at the hospital was 2.6 +/- 1.42 days (range, 1-7
      days). Mean full weight-bearing period of the patients was found out as 13.16 +/-
      2.6 weeks (range, 10-22 weeks). The mean period of union of fracture for patients
      was found out as 19.8 +/- 2.99 weeks (range, 16-34 weeks). CONCLUSION: Treatment
      of distal tibial fractures with MIPPO method provides a successful treatment
      strategy as long as used as per the technique, and it respects and does not harm
      soft tissues which allows early callus formation and rapid healing that enable
      the patient to walk as early as possible after the operation. The overall
      clinical and functional outcome is still good despite minor complications.

PMID- 25861409
TI  - Surgical management of the forefoot in patients with rheumatoid arthritis - a
      review article.
AB  - Foot and ankle pathologies cause a significant disease burden on rheumatoid
      patients. Forefoot pathologies causes pain, callosities and possibly ulceration,
      and can cause problems with footwear. Forefoot correction in rheumatoid patients
      has historically comprised of excision of diseased joints. While satisfaction was
      high with this procedure, complications, changing expectations and improvement in
      medical therapy have raised expectation of patients, physicians and surgeons
      alike. This review assesses the role of joint preserving osteotomies and
      arthrodesis, as well as associated complications. It also describes the role of
      the multidisciplinary team in the management of these patients. 

PMID- 25861410
TI  - Magnetic resonance imaging-based diagnosis of occult osseous injuries in
      traumatic knees.
AB  - BACKGROUND: Occult osseous knee injuries, such as bone bruises, can produce
      persistent pain and functional loss. Although bone bruises cannot be identified
      through direct examination or traditional radiographs, magnetic resonance imaging
      (MRI) has emerged as an effective diagnostic method. Nevertheless, the natural
      history of these injuries remains to be fully defined. Therefore, we used MRI to
      detect and follow bone bruise injuries secondary to knee trauma. METHODS: We
      retrospectively reviewed knee MRIs from patients with bone bruising caused by
      trauma. Occult injuries were initially identified by MRI and subsequently
      rescanned for follow-up at 3 and 9 months. All patients underwent physical
      examinations, direct radiological imaging, and MRI. RESULTS: Although direct
      radiographs showed no abnormalities, we used MRI to identify a total of 22
      patients (age range: 19-42 years; mean: 28 years) with bone bruising. After 3
      months, injuries remained detectable in 68.2% of the subjects, whereas 18.2%
      displayed bone bruising after 9 months. The majority of Type I lesions resolved
      spontaneously, whereas 80% of Type II injuries remained following 3 months, and
      30% persisted at 9 months. Ligament and meniscal lesions were observed in 63.6%
      of patients with bone bruising and appeared to hinder recovery. CONCLUSION: Bone
      bruises generally resolved within 3 to 9 months in subjects with no soft tissue
      lesions and minor trauma. However, ligament and meniscal lesions were observed in
      the majority of patients, and these individuals required longer treatment and
      recuperation. Overall, these findings can contribute to improving the management
      of occult osseous knee injuries.

PMID- 25861411
TI  - Saraca indica bark extract shows in vitro antioxidant, antibreast cancer activity
      and does not exhibit toxicological effects.
AB  - Medicinal plants are used as a complementary and alternative medicine in
      treatment of various diseases including cancer worldwide, because of their ease
      of accessibility and cost effectiveness. Multicomposed mixture of compounds
      present in a plant extract has synergistic activity, increases the therapeutic
      potential many folds, compensates toxicity, and increases bioavailability. Saraca
      indica (family Caesalpiniaceae) is one of the most ancient sacred plants with
      medicinal properties, exhibiting a number of pharmacological effects.
      Antioxidant, antibreast cancer activity and toxicological evaluation of Saraca
      indica bark extract (SIE) were carried out in the present study. The results of
      the study indicated that this herbal preparation has antioxidant and antibreast
      cancer activity. Toxicological studies suggest that SIE is safer to use and may
      have a potential to be used as complementary and alternative medicine for breast
      cancer therapy. 

PMID- 25861412
TI  - Oxidative stress to the cornea, changes in corneal optical properties, and
      advances in treatment of corneal oxidative injuries.
AB  - Oxidative stress is involved in many ocular diseases and injuries. The imbalance
      between oxidants and antioxidants in favour of oxidants (oxidative stress) leads
      to the damage and may be highly involved in ocular aging processes. The anterior
      eye segment and mainly the cornea are directly exposed to noxae of external
      environment, such as air pollution, radiation, cigarette smoke, vapors or gases
      from household cleaning products, chemical burns from splashes of industrial
      chemicals, and danger from potential oxidative damage evoked by them. Oxidative
      stress may initiate or develop ocular injury resulting in decreased visual acuity
      or even vision loss. The role of oxidative stress in the pathogenesis of ocular
      diseases with particular attention to oxidative stress in the cornea and changes
      in corneal optical properties are discussed. Advances in the treatment of corneal
      oxidative injuries or diseases are shown. 

PMID- 25861413
TI  - Sca-1+ cells from fetal heart with high aldehyde dehydrogenase activity exhibit
      enhanced gene expression for self-renewal, proliferation, and survival.
AB  - Stem/progenitor cells from multiple tissues have been isolated based on enhanced
      activity of cytosolic aldehyde dehydrogenase (ALDH) enzyme. ALDH activity has
      emerged as a reliable marker for stem/progenitor cells, such that
      ALDH(bright/high) cells from multiple tissues have been shown to possess enhanced
      stemness properties (self-renewal and multipotency). So far though, not much is
      known about ALDH activity in specific fetal organs. In this study, we sought to
      analyze the presence and activity of the ALDH enzyme in the stem cell antigen-1
      positive (Sca-1+) cells of fetal human heart. Biochemical assays showed that a
      subpopulation of Sca-1+ cells (15%) possess significantly high ALDH1 activity.
      This subpopulation showed increased expression of self-renewal markers compared
      to the ALDH(low) fraction. The ALDH(high) fraction also exhibited significant
      increase in proliferation and pro-survival gene expression. In addition, only the
      ALDH(high) and not the ALDH(low) fraction could give rise to all the cell types
      of the original population, demonstrating multipotency. ALDH(high) cells showed
      increased resistance against aldehyde challenge compared to ALDH(low) cells.
      These results indicate that ALDH(high) subpopulation of the cultured human fetal
      cells has enhanced self-renewal, multipotency, high proliferation, and survival,
      indicating that this might represent a primitive stem cell population within the
      fetal human heart. 

PMID- 25861414
TI  - Chronic kidney disease influences multiple systems: describing the relationship
      between oxidative stress, inflammation, kidney damage, and concomitant disease.
AB  - Chronic kidney disease (CKD) is characterized by increased levels of oxidative
      stress and inflammation. Oxidative stress and inflammation promote renal injury
      via damage to molecular components of the kidney. Unfortunately, relationships
      between inflammation and oxidative stress are cyclical in that the inflammatory
      processes that exist to repair radical-mediated damage may be a source of
      additional free radicals, resulting in further damage to renal tissue. Oxidative
      stress and inflammation also have the ability to become systemic, serving to
      injure tissues distal to the site of original insult. This review describes
      select mediators in the exacerbatory relationship between oxidative stress,
      inflammation, and CKD. This review also discusses oxidative stress, inflammation,
      and CKD as they pertain to the development and progression of common CKD
      associated comorbidities. Lastly, the utility of several widely accessible and
      cost-effective lifestyle interventions and their ability to reduce oxidative
      stress and inflammation are discussed and recommendations for future research are
      provided. 

PMID- 25861415
TI  - Ethanol extract of Innotus obliquus (Chaga mushroom) induces G1 cell cycle arrest
      in HT-29 human colon cancer cells.
AB  - BACKGROUND/OBJECTIVES: Inonotus obliquus (I. obliquus, Chaga mushroom) has long
      been used as a folk medicine to treat cancer. In the present study, we examined
      whether or not ethanol extract of I. obliquus (EEIO) inhibits cell cycle
      progression in HT-29 human colon cancer cells, in addition to its mechanism of
      action. MATERIALS/METHODS: To examine the effects of Inonotus obliquus on the
      cell cycle progression and the molecular mechanism in colon cancer cells, HT-29
      human colon cancer cells were cultured in the presence of 2.5 - 10 ug/mL of EEIO,
      and analyzed the cell cycle arrest by flow cytometry and the cell cycle
      controlling protein expression by Western blotting. RESULTS: Treatment cells with
      2.5 - 10 ug/mL of EEIO reduced viable HT-29 cell numbers and DNA synthesis,
      increased the percentage of cells in G1 phase, decreased protein expression of
      CDK2, CDK4, and cyclin D1, increased expression of p21, p27, and p53, and
      inhibited phosphorylation of Rb and E2F1 expression. Among I. obliquus fractions,
      fraction 2 (fractionated by dichloromethane from EEIO) showed the same effect as
      EEIO treatment on cell proliferation and cell cycle-related protein levels.
      CONCLUSIONS: These results demonstrate that fraction 2 is the major fraction that
      induces G1 arrest and inhibits cell proliferation, suggesting I. obliquus could
      be used as a natural anti-cancer ingredient in the food and/or pharmaceutical
      industry.

PMID- 25861416
TI  - Curcumin utilizes the anti-inflammatory response pathway to protect the intestine
      against bacterial invasion.
AB  - BACKGROUND/OBJECTIVES: Curcumin, a major component of the Curcuma species,
      contains antioxidant and anti-inflammatory properties. Although it was found to
      induce apoptosis in cancer cells, the functional role of curcumin as well as its
      molecular mechanism in anti-inflammatory response, particularly in intestinal
      cells, has been less investigated. The intestine epithelial barrier is the first
      barrier and the most important location for the substrate coming from the lumen
      of the gut. SUBJECTS/METHODS: We administered curcumin treatment in the human
      intestinal epithelial cell lines, T84 and Caco-2. We examined endoplasmic
      reticulum (ER) stress response by thapsigargin, qPCR of XBP1 and BiP,
      electrophysiology by wild-type cholera toxin in the cells. RESULTS: In this
      study, we showed that curcumin treatment reduces ER stress and thereby decreases
      inflammatory response in human intestinal epithelial cells. In addition, curcumin
      confers protection without damaging the membrane tight junction or actin skeleton
      change in intestine epithelial cells. Therefore, curcumin treatment protects the
      gut from bacterial invasion via reduction of ER stress and anti-inflammatory
      response in intestinal epithelial cells. CONCLUSIONS: Taken together, our data
      demonstrate the important role of curcumin in protecting the intestine by
      modulating ER stress and inflammatory response post intoxication.

PMID- 25861417
TI  - Protective role of oligonol from oxidative stress-induced inflammation in C6
      glial cell.
AB  - BACKGROUND/OBJECTIVES: Natural products or active components with a protective
      effect against oxidative stress have attracted significant attention for
      prevention and treatment of degenerative disease. Oligonol is a low molecular
      weight polyphenol containing catechin-type monomers and oligomers derived from
      Litchi chinensis Sonn. We investigated the protective effect and its related
      mechanism of oligonol against oxidative stress. MATERIALS/METHODS: Oxidative
      stress in C6 glial cells was induced by hydrogen peroxide (H2O2) and the
      protective effects of oligonol on cell viability, nitric oxide (NO) and reactive
      oxygen species (ROS) synthesis, and mRNA expression related to oxidative stress
      were determined. RESULTS: Treatment with oligonol inhibited NO and ROS formation
      under cellular oxidative stress in C6 glial cells. In addition, it recovered cell
      viability in a dose dependent-manner. Treatment with oligonol also resulted in
      down-regulated mRNA expression related to oxidative stress, nuclear factor kappa
      B (NF-kappaB) p65, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase
      (iNOS), compared with the control group treated with H2O2. In particular,
      expression of NF-kappaB p65, COX-2, and iNOS was effectively reduced to the
      normal level by treatment with 10 ug/mL and 25 ug/mL of oligonol. CONCLUSIONS:
      These results indicate that oligonol has protective activity against oxidative
      stress-induced inflammation. Oligonol might be a promising agent for treatment of
      degenerative diseases through inhibition of ROS formation and NF-kappaB pathway
      gene expression.

PMID- 25861419
TI  - Effects of quercetin derivatives from mulberry leaves: Improved gene expression
      related hepatic lipid and glucose metabolism in short-term high-fat fed mice.
AB  - BACKGROUND/OBJECTIVES: Mulberry leaves contain quercetin derivatives, which have
      the effects of reducing obesity and improving lipid and glucose metabolism in
      mice with obesity. It is not clear whether or not mulberry leaves can directly
      affect metabolic disorders, in the presence of obesity, because of the
      interaction between obesity and metabolic disorders. The aim of the current study
      was to assess the direct action of quercetin derivatives on metabolic disorders
      in non-obese conditions in short-term high-fat diet fed mice. MATERIALS/METHODS:
      C57BL/6N mice were fed a high-fat diet, supplemented with either 0% (control),
      1%, or 3% mulberry leaf powder (Mul) or 1% catechin powder for five days.
      Anthropometric parameters and blood biochemistry were determined, and hepatic
      gene expression associated with lipid and glucose metabolism was analyzed.
      RESULTS: Body and white fat weights did not differ among the four groups. Plasma
      triglycerides, total cholesterol, and free fatty acids in the 1%, 3% Mul and
      catechin groups did not differ significantly from those of the controls, however,
      plasma glucose and 8-isoprostane levels were significantly reduced. Liver gene
      expression of gp91phox, a main component of NADPH oxidase, was significantly down
      regulated, and PPAR-alpha, related to beta-oxidation, was significantly up
      regulated. FAS and GPAT, involved in lipid metabolism, were significantly down
      regulated, and Ehhadh was significantly up-regulated. Glucose-metabolism related
      genes, L-PK and G6Pase, were significantly down-regulated, while GK was
      significantly up-regulated in the two Mul groups compared to the control group.
      CONCLUSIONS: Our results suggest that the Mul quercetin derivatives can directly
      improve lipid and glucose metabolism by reducing oxidative stress and enhancing
      beta-oxidation. The 1% Mul and 1% catechin groups had similar levels of
      polyphenol compound intake (0.4 * 10(-5) vs 0.4 * 10(-5) mole/5 days) and
      exhibited similar effects, but neither showed dose-dependent effects on lipid and
      glucose metabolism or oxidative stress.

PMID- 25861418
TI  - Active hexose correlated compound potentiates the antitumor effects of low-dose 5
      fluorouracil through modulation of immune function in hepatoma 22 tumor-bearing
      mice.
AB  - BACKGROUND/OBJECTIVES: A variety of immunomodulators can improve the efficacy of
      low-dose chemotherapeutics. Active hexose correlated compound (AHCC), a mushroom
      mycelia extract, has been shown to be a strong immunomodulator. Whether AHCC
      could enhance the antitumor effect of low-dose 5-fluorouracil (5-FU) via
      regulation of host immunity is unknown. MATERIALS/METHODS: In the current study
      Hepatoma 22 (H22) tumor-bearing mice were treated with PBS, 5-FU (10 mg.kg(-1).d(
      1), i.p), or AHCC (360 mg.kg(-1).d(-1), i.g) plus 5-FU, respectively, for 5 d.
      CD3(+), CD4(+), CD8(+), and NK in peripheral blood were detected by flow
      cytometry. ALT, AST, BUN, and Cr levels were measured by biochemical assay. IL-2
      and TNFalpha in serum were measured using the RIA kit and apoptosis of tumor was
      detected by TUNEL staining. Bax, Bcl-2, and TS protein levels were measured by
      immunohistochemical staining and mRNA level was evaluated by RT-PCR. RESULTS:
      Diet consumption and body weight showed that AHCC had no apparent toxicity. AHCC
      could reverse liver injury and myelosuppression induced by 5-FU (P < 0.05).
      Compared to mice treated with 5-FU, mice treated with AHCC plus 5-FU had higher
      thymus index, percentages of CD3(+), CD4(+), and NK cells (P < 0.01), and ratio
      of CD4(+)/CD8(+) (P < 0.01) in peripheral blood. Radioimmunoassay showed that
      mice treated with AHCC plus 5-FU had the highest serum levels of IL-2 and
      TNFalpha compared with the vehicle group and 5-FU group. More importantly, the
      combination of AHCC and 5-FU produced a more potent antitumor effect (P < 0.05)
      and caused more severe apoptosis in tumor tissue (P < 0.05) compared with the 5
      FU group. In addition, the combination of AHCC and 5-FU further up-regulated the
      expression of Bcl-2 associated X protein (Bax) (P < 0.01), while it down
      regulated the expression of B cell lymphoma 2 (Bcl-2) (P < 0.01). CONCLUSIONS:
      These results support the claim that AHCC might be beneficial for cancer patients
      receiving chemotherapy.

PMID- 25861420
TI  - Effects of excessive dietary methionine on oxidative stress and dyslipidemia in
      chronic ethanol-treated rats.
AB  - BACKGROUND/OBJECTIVE: The aim of this study was to examine the effect of high
      dietary methionine (Met) consumption on plasma and hepatic oxidative stress and
      dyslipidemia in chronic ethanol fed rats. MATERIALS/METHODS: Male Wistar rats
      were fed control or ethanol-containing liquid diets supplemented without (E
      group) or with DL-Met at 0.6% (EM1 group) or 0.8% (EM2 group) for five weeks.
      Plasma aminothiols, lipids, malondialdehyde (MDA), alanine aminotransferase
      (ALT), and aspartate aminotransferase were measured. Hepatic folate, S
      adenosylmethionine (SAM), and S-adenosylhomocysteine (SAH) were measured.
      RESULTS: DL-Met supplementation was found to increase plasma levels of
      homocysteine (Hcy), triglyceride (TG), total cholesterol (TC), and MDA compared
      to rats fed ethanol alone and decrease plasma ALT. However, DL-Met
      supplementation did not significantly change plasma levels of HDL-cholesterol,
      cysteine, cysteinylglycine, and glutathione. In addition, DL-Met supplementation
      increased hepatic levels of folate, SAM, SAH, and SAM:SAH ratio. Our data showed
      that DL-Met supplementation can increase plasma oxidative stress and atherogenic
      effects by elevating plasma Hcy, TG, and TC in ethanol-fed rats. CONCLUSION: The
      present results demonstrate that Met supplementation increases plasma oxidative
      stress and atherogenic effects by inducing dyslipidemia and hyperhomocysteinemia
      in ethanol-fed rats.

PMID- 25861421
TI  - The effects of the DASH diet education program with omega-3 fatty acid
      supplementation on metabolic syndrome parameters in elderly women with abdominal
      obesity.
AB  - BACKGROUND/OBJECTIVES: The purpose of this study was to investigate the overall
      effects of a tailored Dietary Approaches to Stop Hypertension (DASH) nutritional
      intervention program which included omega-3 fatty acids supplementation, on
      dietary self-efficacy, dietary knowledge, and dietary behaviors in Korean elderly
      women with abdominal obesity. Furthermore, we investigated the effects of the
      program on metabolic syndrome parameters including the antioxidant capacities in
      these subjects. SUBJECTS/METHODS: A randomized, controlled trial was conducted
      for 8 weeks. The experimental group (n = 21) received a weekly tailored
      nutritional program for 8 weeks and the control group (n = 18) received only one
      educational session. The clinical survey was conducted before and after the
      intervention period. RESULTS: After the intervention, dietary self-efficacy (P =
      0.023), frequency of fruit intake (P = 0.019), and dietary fiber intake (P =
      0.044) were higher in the experimental group than in the control group. The
      oxidative stress (P < 0.001) was lower in the experimental group than in the
      control group. Moreover, low density lipoprotein (LDL) cholesterol (P = 0.023)
      had significantly decreased in the experimental group but not in the control
      group after the intervention. CONCLUSIONS: The intervention program including
      omega-3 fatty acid supplementation had a positive effect on dietary self
      efficacy, dietary behaviors, and oxidative stress among aged women with abdominal
      obesity.

PMID- 25861422
TI  - Effects of sun exposure and dietary vitamin D intake on serum 25-hydroxyvitamin D
      status in hemodialysis patients.
AB  - BACKGROUND/OBJECTIVES: Vitamin D deficiency is common in hemodialysis patients.
      The aim of this study was to identify whether or not sun exposure and dietary
      vitamin D intake have effects on serum 25-hydroxyvitamin D (25(OH)D) status in
      hemodialysis (HD) patients. The objective was to identify the main determinants
      of serum vitamin D status in the study subjects. SUBJECTS/METHODS: A cross
      sectional study of 47 HD patients (19 males and 28 females) was performed. We
      assessed serum 25(OH)D and 1,25(OH)2D levels between August and September 2012
      and analyzed the prevalence of vitamin D deficiency in HD patients. To evaluate
      the determinants of serum 25(OH)D levels, we surveyed dietary vitamin D intake,
      degree of sun exposure, and outdoor activities. To compare biological variables,
      serum 25(OH)D was stratified as below 15 ng/ml or above 15 ng/ml. RESULTS: Mean
      25(OH)D and 1,25(OH)2D levels were 13.5 +/- 5.8 ng/ml and 20.6 +/- 11.8 pg/ml,
      respectively. The proportions of serum 25(OH)D deficiency (< 15 ng/ml),
      insufficiency (15-< 30 ng/ml), and sufficiency (>= 30 ng/ml) in subjects were
      72.4%, 23.4%, and 4.3%, respectively. Prevalence of vitamin D deficiency in
      female patients was 78.6%, whereas that in males was 63.2% (P = 0.046). Vitamin D
      intake and sun exposure time were not significantly different between the two
      stratified serum 25(OH)D levels. Dietary intake of vitamin D did not contribute
      to increased serum 25(OH)D levels in HD patients. The main effective factors
      affecting serum 25(OH)D status were found to be the sun exposure and active
      outdoor exercise. CONCLUSIONS: Hypovitaminosis D is common in HD patients and is
      higher in females than in males. Sun exposure is the most important determinant
      of serum 25(OH)D status in HD patients.

PMID- 25861423
TI  - No short-term effects of calorie-controlled Mediterranean or fast food dietary
      interventions on established biomarkers of vascular or metabolic risk in healthy
      individuals.
AB  - BACKGROUND/OBJECTIVES: This study addressed the question whether the composition
      of supposedly 'healthy' or 'unhealthy' dietary regimes has a calorie-independent
      short-term effect on biomarkers of metabolic stress and vascular risk in healthy
      individuals. SUBJECTS/METHODS: Healthy male volunteers (age 29.5 +/- 5.9 years, n
      = 39) were given a standardized baseline diet for two weeks before randomization
      into three groups of different dietary regimes: fast food, Mediterranean and
      German cooking style. Importantly, the amount of calories consumed per day was
      identical in all three groups. Blood samples were analyzed for biomarkers of
      cardiovascular risk and metabolic stress after two weeks of the baseline diet and
      after two weeks of the assigned dietary regime. RESULTS: No dietary intervention
      affected the metabolic or cardiovascular risk profile when compared in-between
      groups or compared to baseline. Subjects applied to the Mediterranean diet showed
      a statistically significant increase of uric acid compared to baseline and
      compared to the German diet group. Plasma concentrations of urea were
      significantly higher in both the fast food group and the Mediterranean group,
      when compared to baseline and compared to the German diet group. No significant
      differences were detected for the levels of vitamins, trace elements or metabolic
      stress markers (8-hydroxy-2-deoxyguanosine, malondialdehyde and methylglyoxal, a
      potent glycating agent). Established parameters of vascular risk (e.g. LDL
      cholesterol, lipoprotein(a), homocysteine) were not significantly changed in
      between groups or compared to baseline during the intervention period.
      CONCLUSIONS: The calorie-controlled dietary intervention caused neither
      protective nor harmful short-term effects regarding established biomarkers of
      vascular or metabolic risk. When avoiding the noxious effects of overfeeding,
      healthy individuals can possess the metabolic capacity to compensate for a
      potentially disadvantageous composition of a certain diet.

PMID- 25861424
TI  - Relationship between intra-household food distribution and coexistence of dual
      forms of malnutrition.
AB  - BACKGROUND/OBJECTIVES: The relationship between food intake and nutritional
      status has been clearly established. Yet, there are only limited studies on food
      intake among family members and their nutritional status. The study examined the
      relationship between intra-household food distribution and coexistence of dual
      forms of malnutrition (DFM) in the same household. SUBJECTS/METHODS: Households
      with a malnourished child and overweight mother were categorized as DFM. Intra
      household food distribution among family members was reported using ratios, which
      are a measure of individual intakes as compared to all household member intakes
      adjusted to RDA. RESULTS: A 1,899 families were included in the study. The
      prevalence of DFM was 29.8% (95%CI 26.5-31.2). Children consumed lower amounts of
      energy (OR 1.34; 95%CI 1.06-1.69, P = 0.011), carbohydrates (OR 1.2; 95%CI1.03
      1.61, P = 0.022), protein (OR 1.3; 95%CI 1.03-1.64, P = 0.026), and fat (OR 1.3;
      95%CI 1.05-1.66, P = 0.016) than their mothers and other family members. In
      contrast, mothers consumed more carbohydrates than children and other family
      members (OR1.24; 95%CI 1.02-1.51, P = 0.03). CONCLUSIONS: This study is the first
      to report on the food distribution among family members and its relationship with
      occurrence of DFM in Indonesia. The results confirm the occurrence of an unequal
      food distribution between children and mothers, which increases risk of DFM in
      the household. The results also demonstrate that nutritional education at the
      household level is important to increase awareness of the impact of DFM.

PMID- 25861425
TI  - Effect of sodium restriction on blood pressure of unstable or uncontrolled
      hypertensive patients in primary care.
AB  - BACKGROUND/OBJECTIVES: The aims of the present study are: 1) to quantify sodium
      consumption of patients with unstable or uncontrolled hypertension, 2) to
      investigate if reduced sodium intake can lower BP in these patients, and 3), to
      assess the acceptability and feasibility of this approach. SUBJECTS/METHODS: This
      study included 25 adults (age: 50+ years) with frequently elevated BP or patients
      with uncontrolled, uncomplicated hypertension despite drug treatment in a general
      practice setting. BP and salt intake (24h urinary excretion and food records)
      were measured at baseline and after a sodium reduced diet. RESULTS: Mean (+/- SD)
      systolic (SBP) over diastolic (DBP) blood pressure (mmHg) at baseline was 150.7
      (+/- 9.5)/84.149 (+/- 5.6). Mean urinary sodium excretion was 146 mmol/24h. A
      reduction of 28 mmol sodium excretion decreased SBP/DBP to 135.5 (+/- 13.0)/82.5
      (+/- 12.8) (P < 0.001). After one month of no dietary advice, only in 48%, SBP
      was still <=140 mmHg. CONCLUSION: Assessment of sodium intake using food records,
      24h urine collections and probing questions to identify use of sodium containing
      supplements or drugs are essential for tailored advice targeted at sodium intake
      reduction. The results of the present study indicate that reduced sodium intake
      can lower BP after 4 weeks in unstable or uncontrolled hypertensive patients.

PMID- 25861426
TI  - Effects of phylloquinone supplementation on lipid profile in women with
      rheumatoid arthritis: a double blind placebo controlled study.
AB  - BACKGROUND/OBJECTIVES: Rheumatoid arthritis (RA) is associated with an excess
      mortality from cardiovascular disease which is likely attributed to an
      atherogenic lipid profile. Among nutritional factors vitamin K has been recently
      focused as a pivotal nutrient in improvement of lipid related markers. Thus, this
      study was designed to determine the effects of vitamin K on lipid profile in this
      disease. SUBJECTS/METHODS: Fifty eight patients with definitive RA were
      participated in the present double blind placebo controlled study. They were
      randomly allocated into two groups to receive vitamin K1 as phylloquinone [10
      mg/day] (n = 30) or placebo pills (n = 28), for eight weeks. In order to control
      the effects of probable confounders dietary intakes, anthropometric measurements
      including weight and height, clinical status using disease activity score-28 (DAS
      28), physical activity and anxiety status were evaluated at baseline. Moreover,
      serum levels of lipid related markers including total cholesterol (TC), low
      density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol
      (HDL-C) and triglyceride (TG) were measured at baseline and at the end of
      intervention. RESULTS: There were no significant differences between the two
      groups regarding any of the baseline characteristics. After adjusting for some
      relevant confounders, in comparison between two groups, we observed no
      significant changes in lipid related markers at the end of intervention. Also,
      there was no significant difference between before and after intervention values
      within groups (P > 0.05). CONCLUSIONS: Function of vitamin K1 in lipid profile
      modification remains still controversial. This study showed that vitamin K1 has
      no effect on lipid profile in women with rheumatoid arthritis. Further studies
      with a longer follow-up are required to determine the effects of vitamin K on
      atherogenic lipid profile.

PMID- 25861427
TI  - Vitamin E status of 20- to 59-year-old adults living in the Seoul metropolitan
      area of South Korea.
AB  - BACKGROUND/OBJECTIVES: Vitamin E is a fat-soluble vitamin and functions primarily
      as a lipid antioxidant. Inadequate vitamin E status may increase risk of several
      chronic diseases. Thus, the objectives of this study were to estimate intake and
      plasma concentration of each tocopherol and to evaluate vitamin E status of
      Korean adults. SUBJECTS/METHODS: Three consecutive 24-h food recalls and fasting
      blood samples were collected from healthy 20- to 59-y-old adults (33 males and 73
      females) living in the Seoul metropolitan area, South Korea. alpha-, beta-, delta
      , and gamma-tocopherol intakes and plasma concentrations of tocopherols (alpha-,
      delta-, and gamma-tocopherol) were analyzed by gender. RESULTS: Dietary vitamin E
      and total vitamin E intake (dietary plus supplemental vitamin E) was 17.68 +/-
      14.34 and 19.55 +/- 15.78 mg alpha-tocopherol equivalents, respectively. The mean
      daily alpha-tocopherol, and gamma-tocopherol intakes were 3.07 +/- 2.27 mg and
      5.98 +/- 3.74 mg, respectively. Intakes of total vitamin E and each tocopherol of
      males were significantly higher than those of females (P < 0.05). Plasma alpha
      tocopherol concentration was 15.45 +/- 10.16 of males and 15.00 +/- 4.54 umol/L
      of females, respectively. There were no significant differences in plasma
      tocopherol concentrations by gender (P >= 0.05). Plasma alpha-tocopherol was
      negatively correlated with gamma-tocopherol intake (P < 0.05). Twenty-three
      percent of the subjects had plasma alpha-tocopherol concentrations < 12 umol/L
      indicating a biochemical deficiency of vitamin E. Approximately 8% and 9% of
      these participants had plasma alpha-tocopherol:total lipid ratio less than 1.59
      umol/mmol and plasma alpha-tocopherol:total cholesterol ratio less than 2.22
      umol/mmol, respectively, which are also indicative of vitamin E deficiency.
      CONCLUSIONS: Vitamin E intakes of Korean adults were generally adequate with the
      Korean Dietary Reference Intakes for vitamin E. However, alpha-tocopherol intake
      was lower than that reported in other countries, and 23% of the subjects in the
      current study were vitamin E deficient based on plasma alpha-tocopherol
      concentrations.

PMID- 25861428
TI  - Three clustering patterns among metabolic syndrome risk factors and their
      associations with dietary factors in Korean adolescents: based on the Korea
      National Health and Nutrition Examination Survey of 2007-2010.
AB  - BACKGROUND/OBJECTIVE: Even though the prevalence of metabolic syndrome in
      adolescents is increasing, little is presently known about this syndrome in
      adolescents. This study aimed to cluster metabolic risk factors as well as
      examine the associations between identified patterns and nutrient intake using
      data from the Korean National Health Examination and Nutritional Assessment
      (KNHANES). SUBJECTS/METHODS: A total of 2,958 subjects aged 10 to 18 years along
      with both biochemical and dietary data information were obtained from KNHANES
      2007-2010. Six components of metabolic syndrome were used to identify any
      patterns via factor analysis. Individuals were categorized into quartile groups
      according to their pattern score. RESULTS: Three clustering patterns with high
      loadings were identified and named as follows: 1) high blood pressure, 2)
      dyslipidemia, and 3) glucose abnormality patterns. The high blood pressure
      pattern showed high loadings of systolic and diastolic blood pressures, the
      dyslipidemia pattern showed high loadings of triglyceride and HDL-cholesterol
      levels, and the glucose abnormality pattern showed high loadings of fasting blood
      glucose levels. Intakes of fat and riboflavin were significantly decreased,
      whereas those of sodium and niacin were significantly increased across the
      quartiles in the dyslipidemia pattern. No nutrient intake except that of thiamin
      was significantly associated with the high blood pressure or glucose abnormality
      pattern. CONCLUSION: Our findings show that metabolic syndrome risk factors in
      the Korean adolescent population are characterized by three distinct patterns,
      which are differentially associated with dietary factors. Characterizing
      metabolic risk factors and providing specific dietary guidelines for target
      groups are important.

PMID- 25861430
TI  - Erratum: Nutrient intakes of infants with atopic dermatitis and relationship with
      feeding type.
AB  - [This corrects the article on p. 57 in vol. 9, PMID: 25671069.]. 

PMID- 25861429
TI  - Usability of a smartphone food picture app for assisting 24-hour dietary recall:
      a pilot study.
AB  - BACKGROUND/OBJECTIVES: The Recaller app was developed to help individuals record
      their food intakes. This pilot study evaluated the usability of this new food
      picture application (app), which operates on a smartphone with an embedded camera
      and Internet capability. SUBJECTS/METHODS: Adults aged 19 to 28 years (23 males
      and 22 females) were assigned to use the Recaller app on six designated,
      nonconsecutive days in order to capture an image of each meal and snack before
      and after eating. The images were automatically time-stamped and uploaded by the
      app to the Recaller website. A trained nutritionist administered a 24-hour
      dietary recall interview 1 day after food images were taken. Participants'
      opinions of the Recaller app and its usability were determined by a follow-up
      survey. As an evaluation indicator of usability, the number of images taken was
      analyzed and multivariate Poisson regression used to model the factors
      determining the number of images sent. RESULTS: A total of 3,315 food images were
      uploaded throughout the study period. The median number of images taken per day
      was nine for males and 13 for females. The survey showed that the Recaller app
      was easy to use, and 50% of the participants would consider using the app daily.
      Predictors of a higher number of images were as follows: greater interval (hours)
      between the first and last food images sent, weekend, and female. CONCLUSIONS:
      The results of this pilot study provide valuable information for understanding
      the usability of the Recaller smartphone food picture app as well as other
      similarly designed apps. This study provides a model for assisting nutrition
      educators in their collection of food intake information by using tools available
      on smartphones. This innovative approach has the potential to improve recall of
      foods eaten and monitoring of dietary intake in nutritional studies.

PMID- 25861431
TI  - Prevalence and Distribution of BK virus Subtypes in Renal Transplant Recipients
      Referred to Golestan Hospital in Ahvaz, Iran.
AB  - BACKGROUND: BK virus (BKV) belongs to the human Polyomaviridae and the primary
      BKV infection is occurred during childhood then the virus could be latent through
      life, especially in the kidneys and urinary system. It became reactive after an
      immunocompromised status, such as pregnancy or transplantation. Isolated BKV from
      different locations of the world is grouped into four subtypes using serological
      and genotyping methods. The BKV subtype I is the dominant one and has worldwide
      distribution. OBJECTIVES: According to our knowledge, there are no data about the
      BKV prevalence and its genotypes in southwest part of Iran. Considering the high
      prevalence of renal failure and kidney transplant patients in this part, and the
      role of BKV in graft rejection, this study aimed to determine the prevalence of
      BKV infection in renal transplant recipients referred to Golestan Hospital in
      Ahvaz City, Iran. PATIENTS AND METHODS: Urine samples were collected from 122
      kidney transplant recipients referred to Golestan Hospital in Ahvaz, southwest of
      Iran. The extracted DNA was amplified by Polymerase Chain Reaction, and subtype
      of each positive sample was determined using Restriction Fragment Length
      Polymorphism (RFLP) and sequencing methods. RESULTS: From all study population,
      51/122 (41.8%) urine samples were positive for BKV DNA and the other samples were
      negative (71/122). Forty-eight cases (94.11%) were subtype I and 3 others (5.89%)
      were subtype IV using the RFLP method. None of the patient's urine samples were
      positive for subtypes II and III. CONCLUSIONS: Our work is the second study in
      Iran and considering huge numbers of transplantation in Iran and Khuzestan
      Province, south western of Iran, in addition to the role of this virus in kidney
      transplant rejection, routine evaluation of BKV positivity is recommended both
      for graft recipient and donors. This helps better transplantation result and may
      prevent graft rejection.

PMID- 25861432
TI  - Occult hepatitis B infection in patients with cryptogenic liver cirrhosis in
      southwest of iran.
AB  - BACKGROUND: Chronic hepatitis B virus (HBV) infection has a broad spectrum of
      manifestation, ranging from silent carrier state to advanced cirrhosis and
      hepatocellular carcinoma. The persistence of HBV DNA in serum and hepatocytes of
      the cirrhotic patient could be detected by molecular techniques in spite of
      negative HBV serologic markers. OBJECTIVES: This case-control study was designed
      to evaluate the prevalence of occult HBV infection (OBI) in patients with
      cryptogenic liver cirrhosis in comparison with healthy subjects. PATIENTS AND
      METHODS: Of 165 patients with liver cirrhosis, 50 consecutive patients with
      cryptogenic cirrhosis and 80 healthy individual without any risk factors as a
      control group were enrolled in this study. Their sera were tested for HBV DNA
      using nested PCR method. RESULTS: Of 50 patients with cryptogenic cirrhotic, 36
      (72%) were male. The mean age of patients was 53.34 +/- 14.73 years; 80 healthy
      subjects were selected as control group with mean age of 32.65 +/- 8.51 years; 7
      (14%) of the patients with cryptogenic cirrhosis showed positive HBV DNA by PCR,
      while HBV DNA was negative for the control group (P = 0.0001); 4 (57%) cases with
      positive HBV shown by PCR were negative for anti-HBc and anti-HBs tests. The mean
      level of transaminases was significantly higher in patients with cirrhosis. There
      were no significant differences in demographic parameters, transaminases level
      and degree of hepatic failure among cirrhotic patients with and without OBI.
      CONCLUSIONS: The prevalence of OBI was relatively high in patients with
      cryptogenic cirrhosis. OBI was found among the patients above 40 years old.
      Prospective cohort studies are needed to evaluate the clinical significance of
      OBI.

PMID- 25861433
TI  - Identification of Alloiococcus otitidis, Streptococcus pneumoniae, Moraxella
      catarrhalis and Haemophilus influenzae in Children With Otitis Media With
      Effusion.
AB  - BACKGROUND: Based on many studies, otitis media with effusion (OME) is one of the
      major causes of childhood hearing loss, social malformation and medical costs.
      The pathogenesis still remains unclear, though it is known that this complication
      is closely related to bacterial infections. Alloiococcus otitidis, Haemophilus
      influenzae, Streptococcus pneumoniae and Moraxella catarrhalis are the most
      common bacterial pathogens isolated from middle ear effusions (MEEs). OBJECTIVES:
      Due to the prevalence of OME in children, we decided to investigate bacterial
      agents that cause diseases such as A. otitidis, H. influenzae, S. pneumonia and
      M. catarrhalis in these subjects. PATIENTS AND METHODS: Forty-five children
      between one and 15 years of age were selected for this study. Seventy specimens
      were collected from MEE by myringotomy and inoculated in PBS buffer. Conventional
      culture and PCR methods were used for identification of bacterial agents.
      RESULTS: The bacterial cultures in 8.6% of samples were positive by conventional
      culture, with A. otitidis, M. catarrhalis and S. pneumoniae present in 1.4%, 2.9%
      and 4.3% of samples, respectively. No H. influenzae was isolated. By the PCR
      method, A. otitidis was the most frequently isolated bacterium, found in 25.7% of
      samples, followed by S. pneumoniae, M. catarrhalis and H. influenzae, which were
      identified in 20%, 12% and 20% of samples, respectively. Overall, 55 out of 70
      samples were positive by both the PCR and culture method. CONCLUSIONS: It can be
      concluded that A. otitidis was the major causative agent of MEE in children with
      OME. Therefore clinicians should be aware that bacterial infection plays an
      important role in the progression of acute otitis media to OME in children of our
      region.

PMID- 25861434
TI  - Factors associated with delay in diagnosis and treatment of pulmonary
      tuberculosis.
AB  - BACKGROUND: Early treatment of pulmonary tuberculosis (PTB) is necessary for a
      successful tuberculosis (TB) control program. OBJECTIVES: The objective of this
      study was to determine total treatment delay and its associated factors among PTB
      patients in Ahvaz. PATIENTS AND METHODS: A retrospective study was performed
      among newly diagnosed PTB cases registered in 2010 at the Ahvaz health center.
      Total treatment delay was defined as the time interval between the onsets of
      cough to the initiation of anti-TB treatment. Tuberculosis diagnosis and
      treatment was based on the national TB program (NTP). Data analysis was performed
      using the SPSS software by chi-square and Fisher's exact test with odds ratio
      (OR) and 95% confidence interval (CI). RESULTS: The mean age of the patients was
      38.9 +/- 12.3 years; 83 were male and 56 were female. Of the 139 smear positive
      PTB cases, 91 (65.5%) cases had received delayed-treatment. The mean time between
      onset of symptoms, diagnosis and treatment was 73 days (median: 48 days, range: 4
      570 days). Female gender (OR (95% CI): 2.9, 1.03-8.23, P = 0.02), smoking (OR
      (95% CI): 0.49, 0.22-0.96, P = 0.04) and receiving immunosuppressive drugs (OR
      (95% CI): 8.18, 1.09-75.31, P < 0.05) were associated with longer delayed time.
      CONCLUSIONS: Delayed diagnosis and treatment of tuberculosis appears to be the
      main problem in the TB control program of the region. Delayed time is
      significantly associated with female gender, smoking and immunosuppressive drugs.

PMID- 25861435
TI  - Post-vaccination Immunity Against Hepatitis B Virus and Predictors for Non
      responders Among Medical Staff.
AB  - BACKGROUND: Hepatitis B virus (HBV) is a major cause of chronic hepatitis, liver
      cirrhosis, and hepatocellular carcinoma (HCC). HB vaccination is an essential
      step in the prevention of the disease and its consequent complications.
      OBJECTIVES: Immune status of medical personnel in teaching hospitals of Khuzestan
      is not well known. Since these personnel are usually at risk of needle stick and
      other high-risk events, some challenges exist in infection control committee with
      regard to managing these events. This study was conducted to assess post
      vaccination immunity status and non-response to HBV vaccine as well as its
      predictors among medical staff in a teaching hospital affiliated to Ahvaz
      Jundishapur University of Medical Sciences (AJUMS) in Ahvaz, southwest Iran.
      PATIENTS AND METHODS: In this retrospective cross-sectional study, the medical
      staff of a teaching hospital was evaluated for their immune response against HBV
      and factors affecting it. The study conducted in Razi Hospital, Ahvaz City,
      southwest of Iran, in 2013. Demographical, clinical, and laboratory data
      registered in medical files of hospital staff were analyzed by SPSS software
      version 16 using chi-square and Fisher exact tests. Differences with P value <
      0.05 were considered significant. To identify predictors for non-responders, we
      used odds ratio (OR) with 95% confidence interval (CI). RESULTS: Out of 239
      participants, 43 (18 %) were men and 196 (82%) were women. Their mean age was
      31.9 +/- 18.1 years (range of 20 - 55 years). Fourteen (5.9%) participants were
      non-responders, 37 (15.5%) were poor responders, and 188 (78.6%) were good
      responders. The non-responders were older (> 50 years) than the responders (P =
      0.0001), while the body mass index (BMI) was not significantly different (P =
      0.37) between them. Diabetes mellitus (DM) (OR: 7.3, 95% CI, 1.3 - 41.7, P =
      0.05), and using immunosuppressive drugs (ISD) (OR: 3.2, 95% CI, 1.1 - 11.5, P =
      0.03) were two variables in association with non-response to HB vaccine.
      CONCLUSIONS: Non-response rate to HB vaccine in our study was approximately 6%.
      Age over 50 years, DM, and receiving immunosuppressive drugs may be considered as
      predictors for non-response to HB vaccine in medical staff.

PMID- 25861436
TI  - In Vitro Activity of Cordia myxa Mucilage Extract Against Leishmania major and L.
      infantum Promastigotes.

PMID- 25861437
TI  - Prevalence of rhinovirus and respiratory syncytial virus among patients with
      chronic rhinosinusitis.
AB  - BACKGROUND: Chronic rhinosinusitis (CRS) is one of the most common chronic
      illnesses, but the etiology and pathogenesis of CRS are not well understood. Few
      studies have been carried out on the role of viruses in patients with chronic
      sinusitis so far. OBJECTIVES: Regarding the high number of patients, we intended
      to evaluate the prevalence of rhinovirus and respiratory syncytial virus in
      patients with CRS. Doing so, we may pave the way for definitely achieving the
      causes and factors of the disease and consequently definite treatment of this
      debilitating disease in future studies. PATIENTS AND METHODS: This cross
      sectional study was carried out on 76 patients. Sample of the study consisted of
      patients with CRS who were candidates for functional endoscopic sinus surgery
      (FESS). The specimens were collected during FESS between February 2013 and
      December 2013. For this purpose, after entering into sinuses, the specimens were
      collected from their mucus. They were then placed in Dulbecco's modified Eagle's
      viral transport medium (DMEM). They were transferred to the virology lab of the
      university in a cold chain. The specimens were maintained in -70 degrees C before
      examination. Reverse transcriptase-polymerase chain reaction (RT-PCR) was applied
      to explore the presence of rhinovirus and respiratory syncytial virus. RESULTS:
      In this study, 76 patients with rhinosinusitis underwent FESS as qualified
      candidates. The sample of the study consisted of 48 males (63.2%) and 28 females
      (36.8%) with the mean age of 44.3 years and an age range of 19-76 years. Among
      the 76 patients, 53 were with polyps and 23 without polyps. Among the patients,
      66 were candidates of FESS for the first time. Other 11 patients had previously
      undergone the surgery. The results from PCR indicated that 22 (28.94%) patients
      had rhinovirus and 9 (11.84%) had respiratory syncytial virus (RSV). A total of
      25 patients (32.89%) had one of the two viruses. In 6 (7.89%) specimens, both
      viruses were reported. CONCLUSIONS: CRS is a common disease with negative effects
      on the quality of patients' lives. This study showed the high prevalence of these
      two common respiratory viruses in patients with CRS.

PMID- 25861438
TI  - Extracellular enzymes and susceptibility to fluconazole in Candida strains
      isolated from patients with vaginitis and healthy individuals.
AB  - BACKGROUND: Extracellular phospholipase, proteinase, and coagulase are accounted
      as the major virulence factors in Candida albicans. Several reports showed that
      the incidence of resistance to fluconazole has risen during last two decades.
      OBJECTIVES: The present study has investigated the extracellular enzymes of C.
      albicans and non-albicans species isolated from both patients with vaginitis and
      healthy women. In addition, susceptibility of the isolates was evaluated against
      fluconazole. PATIENTS AND METHODS: Vaginal samples were collected using sterile
      cotton swabs and inoculated on CHROMagar Candida. Routine morphological tests and
      ID 32C and API 20C AUX Kits were used to identify species. Phospholipase,
      proteinase, and coagulase activity were determined by standard methods.
      Susceptibility to fluconazole was also evaluated using ATB Fungus 3 Kits.
      RESULTS: The phospholipase activity was detected in 66.7% of the tested isolates
      recovered from patients with vaginitis. In the present study, phospholipase
      activity with higher Pz values (< 0.70) was more common in patients with
      vaginitis (28 of 66 isolates) whereas this rate in the normal individual was 13
      of 42. Proteinase activity was detected in 74.2% and 61.9% of tested isolates
      recovered from patients and normal individuals, respectively. All tested isolates
      were negative for coagulase activity. In the present study, resistance to
      fluconazole was found in 34.8% of isolates. C. dubliniensis was the most common
      isolate (6 out of 11 isolates) that showed resistance to fluconazole.
      CONCLUSIONS: Our results showed that C. albicans was the most frequently isolated
      from both patients with vaginitis and normal individual. In the present study, we
      could not find any correlation between extracellular activities and sources of
      isolates (patients and normal flora) and sensitivity or resistance to
      fluconazole.

PMID- 25861439
TI  - Comparative Study of Esterase and Hemolytic Activities in Clinically Important
      Candida Species, Isolated From Oral Cavity of Diabetic and Non-diabetic
      Individuals.
AB  - BACKGROUND: Diabetes mellitus as a chronic metabolic disease occurs in patients
      with partial or complete deficiency of insulin secretion or disorder in action of
      insulin on tissue. The disease is known to provide conditions for overgrowth of
      Candida species. Candida spp. cause candidiasis by many virulence factors such as
      esterase, hemolysin and phospholipase. OBJECTIVES: This study aimed to compare
      esterase and hemolytic activity in various Candida species isolated from oral
      cavity of diabetic and non-diabetic individuals. PATIENTS AND METHODS: Swab
      samples were taken from 95 patients with diabetes (35 men and 60 women) and 95
      normal persons (42 men and 53 women) and cultured on Sabouraud dextrose agar.
      Identification of isolated yeasts was performed by germ tube test, morphology on
      CHROMagar Candida medium, corn meal agar and ability to grow at 45 degrees C.
      Hemolysin activity was evaluated using blood plate assay and esterase activity
      was determined using the Tween 80 opacity test. RESULTS: Different Candida
      species were isolated from 57 (60%) diabetic and 24 (25%) non-diabetic
      individuals. Esterase activity was detected in all Candida isolates. Only 21.6%
      of C. albicans from patients with diabetes had esterase activity as + 3, while it
      ranged from + 1 to + 2 in others. Hemolytic activity was determined in C.
      albicans, C. dubliniensis, C. glabrata and C. krusei as 0.79, 0.58, 0.66 and
      0.74, respectively. Hemolytic activity was significantly different in the two
      groups of diabetics and non-diabetics. CONCLUSIONS: Oral carriage of C. albicans
      in the diabetic group (n = 42; 66.7%) was significantly greater than the control
      group (n = 16; 57.1%). Esterase activity of C. albicans in diabetic group was
      higher than non-diabetic group. Although C. albicans remains the most frequently
      pathogenic yeast for human, but other species are increasing.

PMID- 25861440
TI  - Diagnostic Value of Serum Adenosine Deaminase (ADA) Level for Pulmonary
      Tuberculosis.
AB  - BACKGROUND: Diagnosis of tuberculosis (TB) is not always easy, thus employing
      methods with a short duration and acceptable sensitivity and specificity is
      necessary to diagnose TB. OBJECTIVES: The aim of this study was to investigate
      the diagnostic value of serum adenosine deaminase (ADA) level for diagnosis of
      pulmonary tuberculosis. PATIENTS AND METHODS: A total of 160 sex and age-matched
      subjects were included in this study, and were divided to four groups; forty
      patients with pulmonary tuberculosis (PTB) diagnosed based on the national TB
      program (NTP), forty patients with non-tuberculosis bacterial pneumonia, forty
      patients with lung cancer and forty people who were healthy in every respect.
      Serum adenosine deaminase activity in patients of each group was measured by the
      Giusti and Galanti calorimetry method using a commercial kit (Diazyme, USA). The
      ANOVA analysis was used to compare groups for quantitative variables. RESULTS:
      Mean serum ADA level in the PTB group was clearly higher than the mean serum ADA
      in the other three groups. Mean serum ADA was 26 IU/L in PTB patients, 19.48 IU/L
      in patients with pneumonia, 15.8 IU/L in patients with lung cancer, and 10.7 IU/L
      in the control group (P < 0.05). In regard to the cut off value of 26 IU/L for
      ADA in patients with PTB sensitivity and specificity was defined as 35% and 91%,
      respectively. CONCLUSIONS: Serum ADA activity with high specificity percentage
      may be a useful alternative test in restricted resource areas to rule out
      diagnosis of PTB. However, serum ADA activity is not a useful tool for TB
      diagnosis.

PMID- 25861441
TI  - Cloning and Expression of Major Surface Antigen 1 Gene of Toxoplasma gondii RH
      Strain Using the Expression Vector pVAX1 in Chinese Hamster Ovary Cells.
AB  - BACKGROUND: Toxoplasmosis is an opportunistic protozoan infection with a high
      prevalence in a broad range of hosts infecting up to one-third of the world human
      population. Toxoplasmosis leads to serious medical problems in immunocompromised
      individuals and fetuses and also induces abortion and mortality in domestic
      animals. Therefore, there is a huge demand for the development of an effective
      vaccine. Surface Antigen 1 (SAG1) is one of the important immunodominant surface
      antigens of Toxoplasma gondii, which interacts with host cells and primarily
      involved in adhesion, invasion and stimulation of host immune response. Surface
      antigen 1 is considered as the leading candidate for development of an effective
      vaccine against toxoplasmosis. OBJECTIVES: The purpose of this study was to clone
      the major surface antigen1 gene (SAG1) from the genotype 1 of T. gondii, RH
      strain into the eukaryotic expression vector pVAX1 in order to use for a DNA
      vaccine. MATERIALS AND METHODS: Genomic DNA was extracted from tachyzoite of the
      parasite using the QIAamp DNA mini kit. After designing the specific primers,
      SAG1 gene was amplified by Polymerase Chain Reaction (PCR). The purified PCR
      products were then cloned into a pPrime plasmid vector. The aforementioned
      product was subcloned into the pVAX1 eukaryotic expression vector. The
      recombinant pVAX1-SAG1 was then transfected into Chinese Hamster Ovary (CHO)
      cells and expression of SAG1 antigen was evaluated using Reverse Transcriptase
      Polymerase Chain Reaction (RT-PCR), Immunofluorescence Assay (IFA) and Western
      Blotting (WB). RESULTS: The cloning and subcloning products (pPrime-SAG1 and
      pVAX1-SAG1 plasmid vectors) of SAG1 gene were verified and confirmed by enzyme
      digestion and sequencing. A 30 kDa recombinant protein was expressed in CHO cells
      as shown by IFA and WB methods. CONCLUSIONS: The pVAX1 expression vector and CHO
      cells are a suitable system for high-level recombinant protein production for
      SAG1 gene from T. gondii parasites and are promising approaches for antigen
      preparation in vaccine development.

PMID- 25861442
TI  - The susceptibility patterns of Candida species isolated from urine samples to
      posaconazole and caspofungin.
AB  - BACKGROUND: Candiduria is a rising condition among hospitalized patients and
      Candida albicans is the most common recovered agent. However, non-albicans
      Candida species (NACs) such as C. glabrata, C. krusei, C. parapsilosis, and C.
      tropicalis are also important. Although most Candida species especially C.
      albicans are sensitive to routinely used antifungals, an increasing trend in
      resistance has been observed among NACs. OBJECTIVES: The aim of the present study
      was to detect the susceptibility of Candida strains recovered from candiduria in
      hospitalized patients against posaconazole and caspofungin. MATERIALS AND
      METHODS: A total of 120 urine samples were taken from patients hospitalized in
      Intensive Care Units (ICUs) (65) and urology (55) wards. All recovered yeasts
      were differentiated by using CHROMagar Candida medium and routine tests for
      identification of Candida species. Minimal inhibitory concentrations (MICs) of
      all isolates towards posaconazole and caspofungin were determined using the
      microdilution method with serial dilutions from 8 to 0.0625 ug/mL (posaconazole)
      and 4 to 0.03125 ug/ mL (caspofungin). RESULTS: In total, 41.7% of urine samples
      were positive for Candida isolation, including C. albicans (46%), C. glabrata
      (24%), C. tropicalis (16%) and C. krusei (14%). The MIC of caspofungin for 90% of
      the tested isolates was lower than 2 ug/mL. Furthermore, 94% of the tested
      isolates were inhibited by posaconazole at lower than 2 ug/mL after 24 hours,
      whereas 6% of isolates had MICs of more than 4 ug/mL. CONCLUSIONS: This study
      demonstrates the importance of Candida species in urine samples from hospitalized
      patients in ICUs and urology wards. It showed that both tested antifungals had
      excellent effects on different species of Candida, however the strains from ICUs
      were found to be more sensitive to caspofungin than posaconazole.

PMID- 25861443
TI  - Simultaneous operation of hydatid cyst of the heart and liver: a case report.
AB  - Primary echinococcosis of the heart is exceptionally uncommon and is reported
      0.5% to 2% of all hydatid cyst sites in comparison with liver (70%) or lung (20%)
      involvement. Hydatid disease of the heart is caused by the cestode tapeworm
      echinococcosis granulosis or alveolaris. We present a 29-year-old female with
      hydatid disease of the liver and heart. She only complained of abdominal pain and
      palpitation. Echocardiography and multi-slice computed tomography (MSCT) showed a
      120*101 mm cyst in the liver and 64 mm in the right ventricular free wall. Both
      cysts were excised within one procedure successfully. 

PMID- 25861444
TI  - Retinoic acid-independent expression of Meis2 during autopod patterning in the
      developing bat and mouse limb.
AB  - BACKGROUND: The bat has strikingly divergent forelimbs (long digits supporting
      wing membranes) and hindlimbs (short, typically free digits) due to the distinct
      requirements of both aerial and terrestrial locomotion. During embryonic
      development, the morphology of the bat forelimb deviates dramatically from the
      mouse and chick, offering an alternative paradigm for identifying genes that play
      an important role in limb patterning. RESULTS: Using transcriptome analysis of
      developing Natal long-fingered bat (Miniopterus natalensis) fore- and hindlimbs,
      we demonstrate that the transcription factor Meis2 has a significantly higher
      expression in bat forelimb autopods compared to hindlimbs. Validation by reverse
      transcriptase and quantitative polymerase chain reaction (RT-qPCR) and whole
      mount in situ hybridisation shows that Meis2, conventionally known as a marker of
      the early proximal limb bud, is upregulated in the bat forelimb autopod from
      CS16. Meis2 expression is localised to the expanding interdigital webbing and the
      membranes linking the wing to the hindlimb and tail. In mice, Meis2 is also
      expressed in the interdigital region prior to tissue regression. This
      interdigital Meis2 expression is not activated by retinoic acid (RA) signalling
      as it is present in the retained interdigital tissue of Rdh10 (trex/trex) mice,
      which lack RA. Additionally, genes encoding RA-synthesising enzymes, Rdh10 and
      Aldh1a2, and the RA nuclear receptor Rarbeta are robustly expressed in bat fore-
      and hindlimb interdigital tissues indicating that the mechanism that retains
      interdigital tissue in bats also occurs independently of RA signalling.
      CONCLUSIONS: Mammalian interdigital Meis2 expression, and upregulation in the
      interdigital webbing of bat wings, suggests an important role for Meis2 in
      autopod development. Interdigital Meis2 expression is RA-independent, and
      retention of interdigital webbing in bat wings is not due to the suppression of
      RA-induced cell death. Rather, RA signalling may play a role in the thinning
      (rather than complete loss) of the interdigital tissue in the bat forelimb, while
      Meis2 may interact with other factors during both bat and mouse autopod
      development to maintain a pool of interdigital cells that contribute to digit
      patterning and growth.

PMID- 25861445
TI  - C-terminal residues of skeletal muscle calsequestrin are essential for calcium
      binding and for skeletal ryanodine receptor inhibition.
AB  - BACKGROUND: Skeletal muscle function depends on calcium signaling proteins in the
      sarcoplasmic reticulum (SR), including the calcium-binding protein calsequestrin
      (CSQ), the ryanodine receptor (RyR) calcium release channel, and skeletal triadin
      95 kDa (trisk95) and junctin, proteins that bind to calsequestrin type 1 (CSQ1)
      and ryanodine receptor type 1 (RyR1). CSQ1 inhibits RyR1 and communicates store
      calcium load to RyR1 channels via trisk95 and/or junctin. METHODS: In this
      manuscript, we test predictions that CSQ1's acidic C-terminus contains binding
      sites for trisk95 and junctin, the major calcium binding domain, and that it
      determines CSQ1's ability to regulate RyR1 activity. RESULTS: Progressive alanine
      substitution of C-terminal acidic residues of CSQ1 caused a parallel reduction in
      the calcium binding capacity but did not significantly alter CSQ1's association
      with trisk95/junctin or influence its inhibition of RyR1 activity. Deletion of
      the final seven residues in the C-terminus significantly hampered calcium
      binding, significantly reduced CSQ's association with trisk95/junctin and
      decreased its inhibition of RyR1. Deletion of the full C-terminus further reduced
      calcium binding to CSQ1 altered its association with trisk95 and junctin and
      abolished its inhibition of RyR1. CONCLUSIONS: The correlation between the number
      of residues mutated/deleted and binding of calcium, trisk95, and junctin suggests
      that binding of each depends on diffuse ionic interactions with several C
      terminal residues and that these interactions may be required for CSQ1 to
      maintain normal muscle function.

PMID- 25861446
TI  - Accidental exposures to peanut in a large cohort of Canadian children with peanut
      allergy.
AB  - BACKGROUND: We previously estimated that the annual rate of accidental exposure
      to peanut in 1411 children with peanut allergy, followed for 2227 patient-years,
      was 11.9% (95% CI, 10.6, 13.5). This cohort has increased to 1941 children,
      contributing 4589 patient-years, and we determined the annual incidence of
      accidental exposure, described the severity, management, location, and identified
      associated factors. FINDINGS: Children with physician-confirmed peanut allergy
      were recruited from Canadian allergy clinics and allergy advocacy organizations
      from 2004 to May 2014. Parents completed questionnaires regarding accidental
      exposure to peanut over the preceding year. Five hundred and sixty-seven
      accidental exposures occurred in 429 children over 4589 patient-years, yielding
      an annual incidence rate of 12.4% (95% CI, 11.4, 13.4). Of 377 accidental
      exposures that were moderate or severe, only 109 (28.9%) sought medical attention
      and of these 109, only 40 (36.7%) received epinephrine. Of the 181
      moderate/severe accidental exposures treated outside a health care facility, only
      11.6% received epinephrine. Thirty-seven percent of accidental exposures occurred
      at home. In multivariate analyses, longer disease duration, recruitment through
      an allergy advocacy association, and having other food allergies decreased the
      likelihood of accidental exposures. Age >= 13 years at study entry and living
      with a single parent increased the risk. CONCLUSION: Despite increased awareness,
      accidental exposures continue to occur, mainly at home, and most are managed
      inappropriately by both health care professionals and caregivers. Consequently,
      more education is required on the importance of strict allergen avoidance and the
      need for prompt and correct management of anaphylaxis.

PMID- 25861448
TI  - Determination of reference intervals for metabolic profile of Hanwoo cows at
      early, middle and late gestation periods.
AB  - BACKGROUND: Metabolic profile was initially designed as a presymptomatic
      diagnostic aid based on statistical analyses of blood metabolites to provide an
      early warning of certain types of metabolic disorder. However, there is little
      metabolic profile data available about Korean Hanwoo cows. Therefore, this study
      aimed to determine the reference intervals of metabolic profile for Korean Hanwoo
      cows. METHODS: Healthy animals (2,205) were selected and divided into early (day
      1 to 95), middle (day 96 to 190) and late (day 191 to 285) period according to
      their gestating period. Metabolic profile including total protein (TP), albumin
      (Alb), urea (UREA), glucose (Glu), total cholesterol (T-Cho), long-chain fatty
      acid (LCFA), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase
      (GGT), creatinine (Crea), calcium (Ca), inorganic phosphorous (iP) and magnesium
      (Mg) were analyzed using a TBA-40FR automatic biochemical analyzer. The data of
      Korean Hanwoo cows were then compared to those of the Japanese Wagyu cows.
      RESULTS: Most of the data of the Korean Hanwoo cows were relatively higher than
      those of Japanese Wagyu cows, with the exception of Glu and GGT. This may
      indicate that the nutritional level of feed for the Korean Hanwoo cows was higher
      than that of the Japanese Wagyu cows because of the different feeding system. In
      particular, relatively higher levels of UREA and LCFA were observed in the Korean
      Hanwoo cows, and this may also contribute to the low reproduction efficiency.
      CONCLUSIONS: These findings may provide some theoretical basis for understanding
      the reproductive and feeding situation of Korean Hanwoo cows.

PMID- 25861447
TI  - Assessment of bone vascularization and its role in bone remodeling.
AB  - Bone is a composite organ that fulfils several interconnected functions, which
      may conflict with each other in pathological conditions. Bone vascularization is
      at the interface between these functions. The roles of bone vascularization are
      better documented in bone development, growth and modeling than in bone
      remodeling. However, every bone remodeling unit is associated with a capillary in
      both cortical and trabecular envelopes. Here we summarize the most recent data on
      vessel involvement in bone remodeling, and we present the characteristics of bone
      vascularization. Finally, we describe the various techniques used for bone vessel
      imaging and quantitative assessment, including histology, immunohistochemistry,
      microtomography and intravital microscopy. Studying the role of vascularization
      in adult bone should provide benefits for the understanding and treatment of
      metabolic bone diseases. 

PMID- 25861449
TI  - "Time's up" - staff's management of mealtimes on inpatient eating disorder units.
AB  - BACKGROUND: Refeeding and normalizing eating behaviour are main treatment aims
      for individuals admitted to inpatient eating disorder units. Consequently,
      mealtime activities are specific, everyday activities, serving a clear
      therapeutic purpose, despite numerous challenges for both staff and patients. Few
      studies have specifically addressed staff involvement, interactions, and
      management activities to structure mealtimes. In this study, we investigated the
      structure of mealtime activities on inpatient eating disorder units, and
      identified associated staff behaviour. METHODS: Descriptive and exploratory
      qualitative study using video observations to investigate the structure of
      mealtimes and staff management of mealtime activities. Forty main meals were
      video recorded and the observational data were analysed using interaction
      analysis. RESULTS: An initial analysis during data screening identified three
      main parts of the meal: 'pre-eating', 'eating', and 'meal completion'. For each
      part, a regular pattern of activities occurred which were associated with staff
      behaviour. CONCLUSIONS: Increased awareness amongst staff regarding how they
      manage the meal and act through a clear internal structure can help staff members
      to further explore their behaviours and collaboration during mealtimes, and also
      contribute to improved interaction with patients during the various phases of the
      meal.

PMID- 25861450
TI  - Mid-gut ACTH-secreting neuroendocrine tumor unmasked with (18)F
      dihydroxyphenylalanine-positron emission tomography.
AB  - Ectopic ACTH Cushing's syndrome (EAS) is often caused by neuroendocrine tumors
      (NETs) of lungs, pancreas, thymus, and other less frequent locations. Localizing
      the source of ACTH can be challenging. A 64-year-old man presented with rapidly
      progressing fatigue, muscular weakness, and dyspnea. He was in poor condition and
      showed facial redness, proximal amyotrophy, and bruises. Laboratory disclosed
      hypokalemia, metabolic alkalosis, and markedly elevated ACTH and cortisol levels.
      Pituitary was normal on magnetic resonance imaging (MRI), and bilateral inferior
      petrosal sinus blood sampling with corticotropin-releasing hormone stimulation
      showed no significant central-to-periphery gradient of ACTH. Head and neck,
      thoracic and abdominal computerized tomography (CT), MRI, somatostatin receptor
      scintigraphy (SSRS), and (18)F-deoxyglucose-positron emission tomography (FDG
      PET) failed to identify the primary tumor. (18)F-dihydroxyphenylalanine (F-DOPA)
      PET/CT unveiled a 20-mm nodule in the jejunum and a metastatic lymph node.
      Segmental jejunum resection showed two adjacent NETs, measuring 2.0 and 0.5 cm
      with a peritoneal metastasis. The largest tumor expressed ACTH in 30% of cells.
      Following surgery, after a transient adrenal insufficiency, ACTH and cortisol
      levels returned to normal values and remain normal over a follow-up of 26 months.
      Small mid-gut NETs are difficult to localize on CT or MRI, and require metabolic
      imaging. Owing to low mitotic activity, NETs are generally poor candidates for
      FDG-PET, whereas SSRS shows poor sensitivity in EAS due to intrinsically low
      tumor concentration of type-2 somatostatin receptors (SST2) or to receptor down
      regulation by excess cortisol. However, F-DOPA-PET, which is related to amine
      precursor uptake by NETs, has been reported to have high positive predictive
      value for occult EAS despite low sensitivity, and constitutes a useful
      alternative to more conventional methods of tumor localization. LEARNING POINTS:
      Uncontrolled high cortisol levels in EAS can be lethal if untreated.Surgical
      excision is the keystone of NETs treatment, thus tumor localization is
      crucial.Most cases of EAS are caused by NETs, which are located mainly in the
      lungs. However, small gut NETs are elusive to conventional imaging and require
      metabolic imaging for detection.FDG-PET, based on tumor high metabolic rate, may
      not detect NETs that have low mitotic activity. SSRS may also fail, due to absent
      or low concentration of SST2, which may be down regulated by excess cortisol.F
      DOPA-PET, based on amine-precursor uptake, can be a useful method to localize the
      occult source of ACTH in EAS when other methods have failed.

PMID- 25861451
TI  - Post-thyroidectomy hypocalcemia exacerbated by chyle leak.
AB  - Transient hypocalcemia after thyroidectomy is not uncommon and the risk increases
      with the extent of neck surgery. We report a case of severe and prolonged
      hypocalcemia after total thyroidectomy complicated by thoracic duct injury.
      Hypoparathyroidism and thoracic duct injury are potential complications following
      total thyroidectomy with extensive lymph node dissection. This case suggested
      that having both conditions may complicate treatment of hypoparathyroid-induced
      hypocalcemia by way of losses of calcium and vitamin D in the chyle leak.
      LEARNING POINTS: This report highlights chyle leak as an uncommon cause of
      prolonged hypocalcemia in patients who have undergone extensive neck
      surgery.Chyle has an electrolyte concentration similar to that of plasma.Medical
      treatment options for a chyle leak include fat-free oral diet or parenteral
      nutrition without oral intake, pharmacological treatment (primarily octreotide).

PMID- 25861452
TI  - Knowledge and perceptions of physicians from private medical centres towards
      generic medicines: a nationwide survey from Malaysia.
AB  - OBJECTIVES: Generic medicine prescribing has become a common practice in public
      hospitals. However, the trend in private medical centres seems to be different.
      The objective of this study was to investigate knowledge, perceptions and
      behavior of physicians from private medical centres in Malaysia regarding generic
      medicines. METHODS: This study was a cross-sectional nationwide survey targeting
      physicians from private medical centres in Malaysia. The survey was conducted
      using questionnaire having (i) background and demographic data of the physicians,
      volume of prescription in a day, stock of generic medicines in their hospital
      pharmacy etc. (ii) their knowledge about bioequivalence (iii) prescribing
      behavior (iv) physicians' knowledge of quality, safety and efficacy of generic
      medicines, and their cost (v) perceptions of physicians towards issues pertaining
      to generic medicines utilization. RESULTS: A total of 263 questionnaires out of
      735 were received, giving a response rate of 35.8%. Of the respondents, 214
      (81.4%) were male and 49 (18.6%) were females. The majority of the participants
      were in the age range of 41-50 years and comprised 49.0% of the respondents. Only
      2.3% of physicians were aware of the regulatory limits of bioequivalence
      standards in Malaysia. Of the respondents, 23.2% agreed that they 'always' write
      their prescriptions using originator product name whereas 50.2% do it 'usually'.
      A number of significant associations were found between their knowledge,
      perceptions about generic medicines and their demographic characteristics.
      CONCLUSIONS: The majority of the physicians from private medical centres in
      Malaysia had negative perceptions about safety, quality and the efficacy of
      generic medicines. These negative perceptions could be the cause of the limited
      use of generic medicines in the private medical centres. Therefore, in order to
      facilitate their use, it is recommended that the physicians need to be reassured
      and educated about the drug regulatory authority approval system of generic
      medicines with regard to their bioequivalence, quality, efficacy and safety.
      Apart from the policy on generic substitution, it would also be recommended to
      have a national medicine pricing policy, which controls drug prices, in both the
      public and private sector. These efforts are worthwhile to reduce the drug
      expenditure and improve the medicine affordability in Malaysia.

PMID- 25861454
TI  - Correction.
AB  - [This corrects the article DOI: 10.1136/lupus-2014-000060.]. 

PMID- 25861453
TI  - Yoga for the Treatment of Insomnia among Cancer Patients: Evidence, Mechanisms of
      Action, and Clinical Recommendations.
AB  - Up to 90% of cancer patients report symptoms of insomnia during and after
      treatment. Symptoms of insomnia include excessive daytime sleepiness, difficulty
      falling asleep, difficulty staying asleep, and waking up too early. Insomnia
      symptoms are among the most prevalent, distressing and persistent cancer- and
      cancer treatment-related toxicities reported by patients, and can be severe
      enough to increase cancer morbidity and mortality. Despite the ubiquity of
      insomnia symptoms, they are under-screened, under-diagnosed, and under-treated in
      cancer patients. When insomnia symptoms are identified, providers are hesitant to
      prescribe, and patients are hesitant to take pharmaceuticals due to polypharmacy
      concerns. In addition, sleep medications do not cure insomnia. Yoga is a well
      tolerated mode of exercise with promising evidence for its efficacy in improving
      insomnia symptoms among cancer patients. This article reviews existing clinical
      research on the effectiveness of yoga for treating insomnia among cancer
      patients. The article also provides clinical recommendations for prescribing yoga
      for the treatment of insomnia in this population.

PMID- 25861455
TI  - Effect of corticosteroid use by dose on the risk of developing organ damage over
      time in systemic lupus erythematosus-the Hopkins Lupus Cohort.
AB  - OBJECTIVES: The impact of corticosteroids on the risk of organ damage in the
      context of clinical end points endorsed in some systemic lupus erythematosus
      (SLE) clinical trials is underexplored. METHODS: We analysed data from the
      Hopkins Lupus Cohort using Cox proportional hazards models to understand the
      impact of exposure to different corticosteroid doses on the risk of developing
      any new organ damage or any new organ damage at the individual organ systems over
      time. RESULTS: Mean prior prednisone dose, recent disease activity and
      immunosuppressant use during follow-up, as well as organ damage score at cohort
      entry, were significant independent predictors of the risk of developing any new
      organ damage. Even after adjustment for recent disease activity, there was a dose
      response relationship across the different levels of exposure to prednisone
      during follow-up and the risk of developing any new organ damage. The risk more
      than doubled in patients exposed to a mean prior prednisone dose of >=20 mg/day
      versus <7.5 mg/day (HR=2.514, p<0.001). It was estimated that a 1 mg/day increase
      in prior prednisone dose during follow-up was associated with a 2.8% increase in
      the risk of developing new organ damage. For individual organ systems, exposure
      to a mean prior prednisone dose of >=7.5 mg/day versus <7.5 mg/day significantly
      increased the risk of developing cataracts (HR=2.41, p<0.001), osteoporotic
      fractures (HR=2.16, p<0.001) and cardiovascular damage (HR=1.54, p=0.041), but
      showed no significant difference for renal damage (HR=1.44, p=0.163) or for other
      individual organ systems. CONCLUSIONS: Organ damage in SLE is multifactorial;
      corticosteroid treatment and disease activity play a role.

PMID- 25861456
TI  - Brain metabolism and autoantibody titres predict functional impairment in
      systemic lupus erythematosus.
AB  - OBJECTIVE: We investigated whether systemic lupus erythematosus (SLE) disease
      duration or serology associate with abnormal regional glucose metabolism as
      measured with [(18)F]2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG
      PET) and deficits on neuropsychological testing. METHODS: Subjects with SLE with
      stable disease activity, without brain damage or clinical symptoms of
      neuropsychiatric (NP) SLE, stratified by disease duration (short-term (ST)
      SLE=disease <=2 years, long-term (LT)-SLE=disease >=10 years), underwent clinical
      assessments, neuropsychological testing, resting FDG-PET scan imaging and
      measurement of serum titres of antibody to N-methyl-d-aspartate receptor (DNRAb).
      FDG-PET scans were compared with age-matched and gender-matched healthy controls.
      RESULTS: Subjects with LT-SLE demonstrated hypometabolism in the prefrontal and
      premotor cortices that correlated with accrued SLE-related damage, but not with
      DNRAb titre or performance on NP testing. Independent of disease duration,
      subjects with SLE demonstrated hypermetabolism in the hippocampus and
      orbitofrontal cortex that correlated with impaired memory performance and mood
      alterations (depression, anxiety, fatigue). Serum DNRAb also correlated
      independently with impaired memory performance and increased anxiety. Together,
      serum DNRAb titre and regional hypermetabolism were more powerful predictors of
      performance than either alone. INTERPRETATION: The presence of serum DNRAbs can
      account for some aspects of brain dysfunction in patients with SLE, and the
      addition of regional measurements of resting brain metabolism improves the
      assessment and precise attribution of central nervous system manifestations
      related to SLE.

PMID- 25861457
TI  - Preliminary test of the LFA rapid evaluation of activity in lupus (LFA-REAL): an
      efficient outcome measure correlates with validated instruments.
AB  - OBJECTIVE: Current disease activity measures for systemic lupus erythematosus
      (SLE) are difficult to score or interpret and problematic for use in clinical
      practice. Lupus Foundation of America (LFA)-Rapid Evaluation of Activity in Lupus
      (REAL) is a pilot application composed of anchored visual analogue scores (0-100
      mm each) for each organ affected by lupus. This study evaluated the use of LFA
      REAL in capturing SLE disease activity. METHODS: In a preliminary test of LFA
      REAL, this simplified, organ-based system was compared with the most widely used
      outcome measures in clinical trials, the British Isles Lupus Assessment Group
      2004 Index (BILAG), the SLE Disease Activity Index (SLEDAI) and the Safety of
      Estrogens in Lupus Erythematosus National Assessment (SELENA) SLEDAI Physician's
      Global Assessment (SS-PGA). The level of agreement was analysed using Spearman
      rank correlations. RESULTS: 91 patients with SLE with mild to severe disease
      activity were evaluated, their median SLEDAI score was 4.0 (range 0-28) and BILAG
      score 8.0 (0-32). The median SS-PGA was 38 mm (4-92) versus the total REAL 50 mm
      (0-268), which expands in range by additive organ scores. Thirty-three patients
      had moderate to severe disease activity (>=1.5 on SS-PGA landmarks). The median
      SS-PGA score of this group was 66 mm (50-92) versus median REAL score of 100 mm
      (59-268), confirming ability to detect a wider distribution of scores at higher
      disease activity. Total REAL correlated with SLEDAI, BILAG and SS-PGA
      (correlation coefficient=0.816, 0.933 and 0.903, respectively; p<0.001 for all).
      Individual LFA-REAL organ scores for musculoskeletal and mucocutaneous also
      correlated with corresponding BILAG domain scores (correlation coefficient=0.925
      and 0.934, p<0.001). CONCLUSIONS: In this preliminary exercise, there were strong
      correlations between LFA-REAL and validated lupus disease activity indices.
      Further development may be valuable for consistent scoring in clinical trials,
      grading optimal assessment of change in disease activity and reliable monitoring
      of patients in practice.

PMID- 25861459
TI  - Association of the interferon signature metric with serological disease
      manifestations but not global activity scores in multiple cohorts of patients
      with SLE.
AB  - OBJECTIVES: The interferon (IFN) signature (IS) in patients with systemic lupus
      erythematosus (SLE) includes over 100 genes induced by type I IFN pathway
      activation. We developed a method to quantify the IS using three genes-the IS
      metric (ISM)-and characterised the clinical characteristics of patients with SLE
      with different ISM status from multiple clinical trials. METHODS: Blood
      microarray expression data from a training cohort of patients with SLE confirmed
      the presence of the IS and identified surrogate genes. We assayed these genes in
      a quantitative PCR (qPCR) assay, yielding an ISM from the IS. The association of
      ISM status with clinical disease characteristics was assessed in patients with
      extrarenal lupus and lupus nephritis from four clinical trials. RESULTS: Three
      genes, HERC5, EPSTI and CMPK2, correlated well with the IS (p>0.96), and composed
      the ISM qPCR assay. Using the 95th centile for healthy control data, patients
      with SLE from different studies were classified into two ISM subsets-ISM-Low and
      ISM-High-that are longitudinally stable over 36 weeks. Significant associations
      were identified between ISM-High status and higher titres of anti-dsDNA
      antibodies, presence of anti extractable nuclear antigen autoantibodies, elevated
      serum B cell activating factor of the tumour necrosis factor family (BAFF)
      levels, and hypocomplementaemia. However, measures of overall clinical disease
      activity were similar for ISM-High and ISM-Low groups. CONCLUSIONS: The ISM is an
      IS biomarker that divides patients with SLE into two subpopulations-ISM-High and
      ISM-Low-with differing serological manifestations. The ISM does not distinguish
      between high and low disease activity, but may have utility in identifying
      patients more likely to respond to treatment(s) targeting IFN-alpha.
      CLINICALTRIALSGOV REGISTRATION NUMBER: NCT00962832.

PMID- 25861460
TI  - Redefining cutaneous lupus erythematosus: a proposed international consensus
      approach and results of a preliminary questionnaire.
AB  - There is currently no uniform definition of cutaneous lupus erythematosus (CLE)
      upon which to base a study population for observational and interventional
      trials. A preliminary questionnaire was derived from and sent to a panel of CLE
      experts which demonstrated consensus agreement that (1) there is a need for new
      definitions for CLE (2) CLE is distinct from systemic lupus erythematosus and
      that a CLE grouping scheme should remain apart from current systemic lupus
      erythematosus schema (3) current CLE grouping schemes are inadequate around
      communication, prognostic information and to meet the needs of researchers,
      clinicians, patients and payers. 

PMID- 25861458
TI  - Haematological manifestations of lupus.
AB  - Our purpose was to compile information on the haematological manifestations of
      systemic lupus erythematosus (SLE), namely leucopenia, lymphopenia,
      thrombocytopenia, autoimmune haemolytic anaemia (AIHA), thrombotic
      thrombocytopenic purpura (TTP) and myelofibrosis. During our search of the
      English-language MEDLINE sources, we did not place a date-of-publication
      constraint. Hence, we have reviewed previous as well as most recent studies with
      the subject heading SLE in combination with each manifestation. Neutropenia can
      lead to morbidity and mortality from increased susceptibility to infection.
      Severe neutropenia can be successfully treated with granulocyte colony
      stimulating factor. While related to disease activity, there is no specific
      therapy for lymphopenia. Severe lymphopenia may require the use of prophylactic
      therapy to prevent select opportunistic infections. Isolated idiopathic
      thrombocytopenic purpura maybe the first manifestation of SLE by months or even
      years. Some manifestations of lupus occur more frequently in association with low
      platelet count in these patients, for example, neuropsychiatric manifestation,
      haemolytic anaemia, the antiphospholipid syndrome and renal disease.
      Thrombocytopenia can be regarded as an important prognostic indicator of survival
      in patients with SLE. Medical, surgical and biological treatment modalities are
      reviewed for this manifestation. First-line therapy remains glucocorticoids.
      Through our review, we conclude glucocorticoids do produce a response in majority
      of patients initially, but sustained response to therapy is unlikely.
      Glucocorticoids are used as first-line therapy in patients with SLE with AIHA,
      but there is no conclusive evidence to guide second-line therapy. Rituximab is
      promising in refractory and non-responding AIHA. TTP is not recognised as a
      criteria for classification of SLE, but there is a considerable overlap between
      the presenting features of TTP and SLE, and a few patients with SLE have
      concurrent TTP. Myelofibrosis is an uncommon yet well-documented manifestation of
      SLE. We have compiled the cases that were reported in MEDLINE sources. 

PMID- 25861462
TI  - The benefit of sirolimus maintenance immunosuppression and rabbit antithymocyte
      globulin induction in liver transplant recipients that develop acute kidney
      injury in the early postoperative period.
AB  - Published data are limited describing renal outcomes in orthotopic liver
      transplant (OLT) recipients prescribed sirolimus (SRL) maintenance
      immunosuppression (MIS) and rabbit antithymocyte globulin (rATG) induction. We
      investigated whether SRL MIS and rATG induction facilitated recovery of acute
      kidney injury in the early postoperative period. This retrospective descriptive
      study screened 308 consecutive OLTs performed between 2006 and 2009. All patients
      received rATG induction with steroid avoidance. MIS consisted of SRL or TAC with
      mycophenolate mofetil. A total of 197 patients were included: 168 (85%) received
      TAC and 29 (15%) received SRL for a median of 365 days. Demographics were similar
      between groups except for a higher incidence of pretransplant renal dysfunction
      in the SRL recipients (SRL 59% versus TAC 21%; P < 0.05). The eGFR was
      significantly (P < 0.05) higher for all time points in the TAC group with the
      exception of month 2. However, improvement in eGFR was significantly (P < 0.05)
      greater in the SRL group postoperatively. Our study suggests that rATG induction
      and SRL maintenance immunosuppression facilitate renal recovery for liver
      transplant recipients that develop acute kidney injury in the early postoperative
      period. 

PMID- 25861461
TI  - Immune Signaling and Antimicrobial Peptide Expression in Lepidoptera.
AB  - Many lepidopteran insects are agricultural pests that affect stored grains, food
      and fiber crops. These insects have negative ecological and economic impacts
      since they lower crop yield, and pesticides are expensive and can have off-target
      effects on beneficial arthropods. A better understanding of lepidopteran immunity
      will aid in identifying new targets for the development of specific insect pest
      management compounds. A fundamental aspect of immunity, and therefore a logical
      target for control, is the induction of antimicrobial peptide (AMP) expression.
      These peptides insert into and disrupt microbial membranes, thereby promoting
      pathogen clearance and insect survival. Pathways leading to AMP expression have
      been extensively studied in the dipteran Drosophila melanogaster. However,
      Diptera are an important group of pollinators and pest management strategies that
      target their immune systems is not recommended. Recent advances have facilitated
      investigation of lepidopteran immunity, revealing both conserved and derived
      characteristics. Although the general pathways leading to AMP expression are
      conserved, specific components of these pathways, such as recognition proteins
      have diverged. In this review we highlight how such comparative immunology could
      aid in developing pest management strategies that are specific to agricultural
      insect pests. 

PMID- 25861463
TI  - Decreased Perifoveal Sensitivity Detected by Microperimetry in Patients Using
      Hydroxychloroquine and without Visual Field and Fundoscopic Anomalies.
AB  - Purpose. To evaluate the usefulness of microperimetry in the early detection of
      the ocular anomalies associated with the use of hydroxychloroquine. Methods.
      Prospective comparative case series study comprising 14 healthy eyes of 7
      patients (group A) and 14 eyes of 7 patients under treatment with
      hydroxychloroquine for the treatment of rheumatologic diseases and without
      fundoscopic or perimetric anomalies (group B). A comprehensive ophthalmological
      examination including microperimetry (MP) and spectral-domain optical coherence
      tomography was performed in both groups. Results. No significant differences were
      found in mean MP foveal sensitivity between groups (P = 0.18). However, mean MP
      overall sensitivity was significantly higher in group A (29.05 +/- 0.57 dB versus
      group B, 26.05 +/- 2.75 dB; P < 0.001). Significantly higher sensitivity values
      were obtained in group A in comparison to group B for the three eccentric loci
      evaluated (P < 0.001). Conclusion. Microperimetry seems to be a useful tool for
      the early detection of retinal damage in patients treated with
      hydroxychloroquine. 

PMID- 25861464
TI  - Intraocular Lens Opacification following Intracameral Injection of Recombinant
      Tissue Plasminogen Activator to Treat Inflammatory Membranes after Cataract
      Surgery.
AB  - Purpose. To report 7 cases of intraocular lens (IOL) opacification following
      treatment of postoperative anterior chamber fibrin with recombinant tissue
      plasminogen activator (rtPA) after cataract surgery. Methods. Retrospective case
      series of 7 eyes in 7 patients who developed IOL opacification after receiving
      rtPA for anterior chamber inflammatory membrane formation resulting from
      phacoemulsification cataract surgery. Three explanted IOLs were investigated with
      light microscopy, histochemical analysis, scanning electron microscopy, and X-ray
      spectrometry. Results. All patients underwent uncomplicated cataract surgery and
      posterior chamber hydrophilic IOL implantation. Anterior chamber inflammatory
      membranes developed between 1 and 4 weeks of surgery and were treated with
      intracameral rtPA. IOL opacification was noted between 4 weeks and 6 years after
      rtPA treatment with reduced visual acuity, and IOL exchange was carried out in 3
      patients. Light microscopy evaluation revealed diffuse fine granular deposits on
      the anterior surface/subsurface of IOL optic that stained positive for calcium
      salts. Scanning electron microscopy (SEM) and energy-dispersive X-ray
      spectrometry (EDS) confirmed the presence of calcium and phosphate on the IOL.
      Conclusions. Intracameral rtPA, though rapidly effective in the treatment of
      anterior chamber inflammatory membranes following cataract surgery, may be
      associated with IOL opacification. 

PMID- 25861465
TI  - Modulation of miRNAs in Pulmonary Hypertension.
AB  - MicroRNAs (miRNAs) have emerged as a new class of posttranscriptional regulators
      of many cardiac and vascular diseases. They are a class of small, noncoding RNAs
      that contributes crucial roles typically through binding of the 3'-untranslated
      region of mRNA. A single miRNA may influence several signaling pathways
      associated with cardiac remodeling by targeting multiple genes. Pulmonary
      hypertension (PH) is a rare disorder characterized by progressive obliteration of
      pulmonary (micro) vasculature that results in elevated vascular resistance,
      leading to right ventricular hypertrophy (RVH) and RV failure. The pathology of
      PH involves vascular cell remodeling including pulmonary arterial endothelial
      cell (PAEC) dysfunction and pulmonary arterial smooth muscle cell (PASMC)
      proliferation. There is no cure for this disease. Thus, novel intervention
      pathways that govern PH induced RVH may result in new treatment modalities.
      Current therapies are limited to reverse the vascular remodeling. Recent studies
      have demonstrated the roles of various miRNAs in the pathogenesis of PH and
      pulmonary disorders. This review provides an overview of recent discoveries on
      the role of miRNAs in the pathogenesis of PH and discusses the potential for
      miRNAs as therapeutic targets and biomarkers of PH at clinical setting. 

PMID- 25861466
TI  - Slipping through the Cracks: Linking Low Immune Function and Intestinal Bacterial
      Imbalance to the Etiology of Rheumatoid Arthritis.
AB  - Autoimmune diseases (ADs) are considered to be caused by the host immune system
      which attacks and destroys its own tissue by mistake. A widely accepted
      hypothesis to explain the pathogenic mechanism of ADs is "molecular mimicry,"
      which states that antibodies against an infectious agent cross-react with a self
      antigen sharing an identical or similar antigenic epitope. However, this
      hypothesis was most likely established based on misleading antibody assay data
      largely influenced by intense false positive reactions involved in immunoassay
      systems. Thus reinvestigation of this hypothesis using an appropriate blocking
      agent capable of eliminating all types of nonspecific reactions and proper assay
      design is strongly encouraged. In this review, we discuss the possibility that
      low immune function may be the fundamental, common defect in ADs, which increases
      the susceptibility to potential disease causative pathogens located in the
      gastrointestinal tract (GI), such as bacteria and their components or dietary
      components. In addition to these exogenous agents, aberrations in the host's
      physical condition may disrupt the host defense system, which is tightly
      orchestrated by "immune function," "mucosal barrier function," and "intestinal
      bacterial balance." These disturbances may initiate a downward spiral, which can
      lead to chronic health problems that will evolve to an autoimmune disorder. 

PMID- 25861467
TI  - Tissue factor expression in obese type 2 diabetic subjects and its regulation by
      antidiabetic agents.
AB  - OBJECTIVE: Increased coagulation activation may contribute to the high incidence
      of cardiovascular complications observed in obese and type 2 diabetes (T2D)
      subjects. Although tissue factor (TF), the primary initiator of coagulation is
      increased in obesity, its expression in adipose tissues and its association with
      metabolic parameters are unclear. We sought to compare TF expression in plasma
      and adipose tissues of obese subjects with and without T2D, its correlation with
      metabolic parameters, and regulation in response to antidiabetic drugs. METHODS:
      Subjects were recruited from diabetes clinics and adipose tissue was obtained by
      needle biopsy of lower subcutaneous abdominal depot. For the intervention study,
      subjects were randomized into treatment groups with rosiglitazone or metformin
      for 4 months. RESULTS: Plasma TF antigen, activity, and adipose TF mRNA were
      greater in obese T2D subjects compared with obese nondiabetics. Plasma TF
      activity correlated with fasting insulin, glucose, and free fatty acids, (FFAs),
      and adipose TF mRNA correlated with plasma FFA. Plasma TF activity was reduced by
      metformin and increased with rosiglitazone treatment. CONCLUSIONS: Specific
      diabetes-related metabolic parameters, but not obesity per se, are correlated
      with TF expression. Regulation of TF activity by different classes of
      antidiabetic drugs may relate to protective or adverse cardiovascular outcomes.

PMID- 25861468
TI  - The impact of parents' categorization of their own weight and their child's
      weight on healthy lifestyle promoting beliefs and practices.
AB  - OBJECTIVE: To evaluate parents' beliefs and practices related to childhood
      obesity and determine if these are influenced by parent's perception of their own
      weight or their child's weight. METHODS: Parents of obese (n = 689) or normal
      weight (n = 1122) children 4-15 years in Georgia, USA, were randomly selected to
      complete a telephone survey. Frequency of child obesity-related perceptions,
      beliefs, and practices were assessed, stratified by parent-perceived self-weight
      and child weight status, and compared using Chi-squared tests and multivariate
      logistic regression. RESULTS: Most parents, regardless of perceived child weight,
      agreed that child overweight/obesity can cause serious illness (95%) but only one
      half believed it was a problem in Georgia. Many (42.4%) failed to recognize
      obesity in their own children. More parents who perceived their child as
      overweight versus normal weight reported concern about their child's diet and
      activity and indicated readiness for lifestyle change. Parents' perception of
      their own weight had little additional impact. CONCLUSIONS: While awareness of
      child overweight as a modifiable health risk is high, many parents fail to
      recognize it in their own families and communities, reducing the likelihood of
      positive lifestyle change. Additional efforts to help parents understand their
      role in facilitating behavior change and to assist them in identifying at-risk
      children are required.

PMID- 25861469
TI  - Serum cholesterol reduction efficacy of biscuits with added plant stanol ester.
AB  - This study's aim was to test the low-density lipoprotein cholesterol- (LDL-c-)
      lowering efficacy of biscuits containing 2 g of plant stanols, which corresponded
      to 3.4 g of plant stanol esters. The biscuit is a new food format that can be
      consumed as a snack. In a double-blind, placebo-controlled parallel design study,
      119 mildly to moderately hypercholesterolemic volunteers were randomized to plant
      stanol or control groups. Subjects were comparable in age, gender, lipid
      profiles, and body mass index. They consumed a control biscuit once a day for a
      two-week period, followed by a four-week intervention period that either had a
      plant stanol ester biscuit or a control. During the habitual diet, one biscuit
      per day was consumed at any time that subjects wished. Serum lipid profiles were
      measured at the first day of run-in, at baseline, and at the study's end.
      Compared to the control, the total cholesterol (TC), LDL-c, and the LDL-to-high
      density lipoprotein (LDL/HDL) ratio had serum reductions of 4.9%, 6.1%, and 4.3%,
      respectively, and were observed after 4 weeks of biscuit consumption with added
      plant stanols (P < 0.05). A significantly higher reduction in LDL-c (8.9%) and
      LDL/HDL ratio (11.4%) was measured in those taking a plant stanol biscuit with a
      meal compared to those who consumed a plant stanol biscuit without other food. In
      conclusion, incorporating plant stanols into a biscuit is an attractive,
      convenient, and acceptable way to modestly lower elevated cholesterol
      concentrations. For optimal efficacy, biscuits should be consumed with a meal as
      part of a healthy diet. 

PMID- 25861470
TI  - Free flap transfer to preserve main arterial flow in early reconstruction of open
      fracture in the lower extremity.
AB  - The selection of recipient vessels is crucial when reconstructing traumatized
      lower extremities using a free flap. When the dorsalis pedis artery and/or
      posterior tibial artery cannot be palpated, we utilize computed tomography
      angiography to verify the site of vascular injury prior to performing free flap
      transfer. For vascular anastomosis, we fundamentally perform end-to-side
      anastomosis or flow-through anastomosis to preserve the main arterial flow. In
      addition, in open fracture of the lower extremity, we utilize the anterolateral
      thigh flap for moderate soft tissue defects and the latissimus dorsi
      musculocutaneous flap for extensive soft tissue defects. The free flaps used in
      these two techniques are long and include a large-caliber pedicle, and
      reconstruction can be performed with either the anterior or posterior tibial
      artery. The preparation of recipient vessels is easier during the acute phase
      early after injury, when there is no influence of scarring. A free flap allows
      flow-through anastomosis and is thus optimal for open fracture of the lower
      extremity that requires simultaneous reconstruction of main vessel injury and
      soft tissue defect from the middle to distal thirds of the lower extremity. 

PMID- 25861471
TI  - Clinical features of primary vein grafts in free tissue transfers.
AB  - The outcomes of free tissue transfers combined with vein grafts have been
      inconsistent, and discussions continue regarding their appropriate use. Of the
      142 free tissue transfers that we performed from January 2004 to December 2011,
      we retrospectively analyzed 15 consecutive patients who underwent free tissue
      transfers in combination with vein grafts. Etiologies included trauma (8
      patients), infection (4), and tumor (3). Types of free tissue transfers were
      fibula (4), anterolateral thigh (3), groin (3), jejunum (3), latissimus dorsi
      (1), and dorsal pedis (1). Vein grafts were used for the artery (6), vein (2), or
      both (7). The donor veins were the saphenous vein (12) and the external jugular
      vein (3). The mean length of the grafted veins was 10.8 cm (range: 4-18 cm). Even
      though complications of congestion occurred in 2 patients, these flaps survived
      by reexploration. The flap success rate was 15 of 15 (100%) of vein grafted free
      flaps versus 124 of 127 (97.6%) of free flaps not requiring vein grafts. To
      improve the success rate of free tissue transfers combined with vein grafts,
      securing healthy recipient vessels, meticulous surgical handling, a reliable
      vascular anastomosis technique, and strict postoperative monitoring are crucial. 

PMID- 25861472
TI  - Noninterventional study of transdermal fentanyl (fentavera) matrix patches in
      chronic pain patients: analgesic and quality of life effects.
AB  - Fentanyl is considered to be an effective, transdermal treatment of chronic,
      cancer, and noncancer pain. This noninterventional, clinical practice-based
      study, on 426 patients attending 42 practices, assessed a proprietary, Aloe vera
      containing, transdermal fentanyl matrix patch (Fentavera), for its analgesic
      effects, patients' quality of life (QoL) effects, tolerability, and adhesiveness.
      Study outcomes were mean changes from baseline of patient (11-point scales) and
      physician (5-point scales) ratings. After 1 and 2 months treatment, there were
      significant (P < 0.0001) decreases in patients' ratings of pain intensity, and
      impairment of walking, general activity, sleep quality, and QoL. For each
      parameter, the patient response rate was >30% at 2 months (response = 2-point
      decrease on 11-point rating scale). In a large majority of patients, the
      physicians rated the matrix patch as good or very good for analgesic effect,
      systemic and local tolerance, and adhesiveness. There were 30 adverse events in
      4.2% of patients and analgesic comedications were reduced during treatment
      compared to before treatment. It is concluded, from this population-based data,
      that the proprietary, transdermal fentanyl matrix patch is effective and safe for
      chronic pain management in clinical practice, with significant positive analgesic
      and QoL effects, while being well tolerated and exhibiting good or very good
      adhesiveness. 

PMID- 25861473
TI  - Biological motion perception is affected by age and cognitive style in children
      aged 8-15.
AB  - The current paper aims to address the question of how biological motion
      perception in different social contexts is influenced by age or also affected by
      cognitive styles. We examined developmental changes of biological motion
      perception among 141 school children aged 8-15 using point-light displays in
      monadic and dyadic social contexts. Furthermore, the cognitive styles of
      participants were investigated using empathizing-systemizing questionnaires.
      Results showed that the age and empathizing ability strongly predicted
      improvement in action perception in both contexts. However the systemizing
      ability was an independent predictor of performance only in monadic contexts.
      Furthermore, accuracy of action perception increased significantly from 46.4% (SD
      = 16.1) in monadic to 62.5% (SD = 11.5) in dyadic social contexts. This study can
      help to identify the roles of social context in biological motion perception and
      shows that children with different cognitive styles may present different
      biological motion perception. 

PMID- 25861474
TI  - Comparison of percutaneous endoscopic lumbar discectomy and open lumbar surgery
      for adjacent segment degeneration and recurrent disc herniation.
AB  - Objective. The goal of the present study was to examine the clinical results of
      percutaneous endoscopic lumbar discectomy (PELD) and open lumbar surgery for
      patients with adjacent segment degeneration (ASD) and recurrence of disc
      herniation. Methods. From December 2011 to November 2013, we collected forty
      three patients who underwent repeated lumbar surgery. These patients, either
      received PELD (18 patients) or repeated open lumbar surgery (25 patients), due to
      ASD or recurrence of disc herniation at L3-4, L4-5, or L5-S1 level, were assigned
      to different groups according to the surgical approaches. Clinical data were
      assessed and compared. Results. Mean blood loss was significantly less in the
      PELD group as compared to the open lumbar surgery group (P < 0.0001). Hospital
      stay and mean operating time were shorter significantly in the PELD group as
      compared to the open lumbar surgery group (P < 0.0001). Immediate postoperative
      pain improvement in VAS was 3.5 in the PELD group and -0.56 in the open lumbar
      surgery group (P < 0.0001). Conclusion. For ASD and recurrent lumbar disc
      herniation, PELD had more advantages over open lumbar surgery in terms of reduced
      blood loss, shorter hospital stay, operating time, fewer complications, and less
      postoperative discomfort. 

PMID- 25861475
TI  - Fat Necrosis of the Breast: A Pictorial Review of the Mammographic, Ultrasound,
      CT, and MRI Findings with Histopathologic Correlation.
AB  - Fat necrosis of the breast is a challenging diagnosis due to the various
      appearances on mammography, ultrasound, CT, PET-CT, and MRI. Although mammography
      is more specific, ultrasound is a very important tool in making the diagnosis of
      fat necrosis. MRI has a wide spectrum of findings for fat necrosis and the
      appearance is the result of the amount of the inflammatory reaction, the amount
      of liquefied fat, and the degree of fibrosis. While CT and PET-CT are not first
      line imaging examinations for the diagnosis of breast cancer or fat necrosis,
      they are frequently performed in the surveillance and staging of disease.
      Knowledge of how fat necrosis presents on these additional imaging techniques is
      important to prevent misinterpretation of the imaging findings. Gross and
      microscopic appearances of fat necrosis depend on the age of the lesion; the
      histologic examination of fat necrosis is usually straightforward. Knowledge of
      the variable appearances of fat necrosis on a vast array of imaging modalities
      will enhance a radiologist's accuracy in the analysis and interpretation of fat
      necrosis versus other diagnoses. 

PMID- 25861476
TI  - Depression and the Overall Burden of Painful Joints: An Examination among
      Individuals Undergoing Hip and Knee Replacement for Osteoarthritis.
AB  - The majority of patients with hip or knee osteoarthritis (OA) report one or more
      symptomatic joints apart from the one targeted for surgical care. Therefore, the
      purpose of the present study was to investigate the association between the
      burden of multiple symptomatic joints and self-reported depression in patients
      awaiting joint replacement for OA. Four hundred and seventy-five patients at a
      single centre were evaluated. Patients self-reported joints that were painful
      and/or symptomatic most days of the previous month on a homunculus, with nearly
      one-third of the sample reporting 6 or more painful joints. The prevalence of
      depression was 12.2% (58/475). When adjusted for age, sex, education level, hip
      or knee OA, body mass index, chronic condition count, and joint-specific WOMAC
      scores, each additional symptomatic joint was associated with a 19% increased
      odds (odds ratio: 1.19 (95% CI: 1.08, 1.31, P < 0.01)) of self-reported
      depression. Individuals reporting 6 or more painful joints had 2.5-fold or
      greater odds of depression when compared to those patients whose symptoms were
      limited to the surgical joint. A focus on the surgical joint alone is likely to
      miss a potentially important determinant of postsurgical patient-reported
      outcomes in patients undergoing hip or knee replacement. 

PMID- 25861477
TI  - Dosing-time dependent effects of sodium nitroprusside on cerebral, renal, and
      hepatic catalase activity in mice.
AB  - To investigate the time dependence of sodium nitroprusside- (NPS-) induced
      oxidative effects, the authors study the variation of the antioxidant enzyme CAT
      activity in various tissues after the administration of a single 2.5 mg/kg dose
      of SNP or sodium chloride (NaCl 0.9%). For each of the two dosing times (1 and 13
      hours after light onset, HALO, which correspond to the beginning of diurnal rest
      span and of nocturnal activity span of mice, resp.), brain, kidney, and liver
      tissues were excised from animals at 0, 1, 3, 6, 9, 12, 24, and 36 h following
      the drug administration and CAT activity was assayed. The results suggest that
      SNP-induced stimulation of CAT activity is greater in all three tissues when the
      drug is administered at 1 HALO than at 13 HALO. Two-way ANOVA revealed that CAT
      activity significantly (P < 0.004) varied as a function of the sampling time but
      not of the treatment in all three tissues. Moreover, a statistically significant
      (P < 0.004) interaction between the organ sampling-time and the SNP treatment was
      revealed in kidney regardless of the dosing time, whereas a highly significant (P
      < 0.0002) interaction was validated in liver only in animals injected at 13 HALO.

PMID- 25861478
TI  - Inheritance Pattern of Temephos Resistance, an Organophosphate Insecticide, in
      Aedes aegypti (L.).
AB  - The present paper reports the mode of inheritance of resistance in laboratory
      induced temephos resistant and susceptible strains of Ae. aegypti. Homozygous
      resistant and susceptible strains of Ae. aegypti were generated by selective
      inbreeding at a diagnostic dose of 0.02 mg/L of temephos. Genetic crosses were
      carried out between these strains to determine the inheritance pattern of
      temephos resistance. The log-dosage probit mortality relationships and degree of
      dominance (D) were calculated. The dosage-mortality (d-m) line of the F 1
      generation was nearer to the resistant parent than the susceptible one. The "D"
      value was calculated as 0.15 indicating that the temephos resistant gene is
      incompletely dominant. The d-m lines of the F 2 generation and progeny from the
      backcross exhibited clear plateaus of mortality across a range of doses
      indicating that temephos resistance is controlled by a single gene. Comparison of
      the mortality data with the theoretical expectations using the chi (2) test
      revealed no significant difference, confirming a monogenic pattern of
      inheritance. In conclusion, the study provides evidence that the temephos
      resistance in Ae. aegypti follows an incompletely dominant and monogenic mode of
      inheritance. 

PMID- 25861479
TI  - Genetic Variant in the CYP19A1 Gene Associated with Coronary Artery Disease.
AB  - The CYP19A1 gene encodes the enzyme aromatase, which is responsible for the
      biosynthesis of estrogens. The rs10046 polymorphism of CYP19A1 gene has been
      investigated in two studies on the occurrence of hypertension, but there are no
      studies on its correlation with coronary artery disease (CAD). We investigated
      189 subjects who were hospitalized at "KAT" General Hospital of Athens and
      underwent coronary angiography. Of these, 123 were found with CAD with an average
      age of 60 years and constituted the patients group and 66 subjects with an
      average age of 58 years without damage in the coronary vessels and constituted
      the control group (healthy). The frequencies of genotypes CC, CT, and TT of
      rs10046 polymorphism are significantly different between the group of CAD
      patients and the control group (0.34, 0.48, and 0.18 versus 0.20, 0.48, and 0.32,
      resp., P = 0.034) as the frequency of C allele (0.58 versus 0.44, resp., OR =
      1.771 and P = 0.010). We found similar results for men, but not for women (small
      sample). The results of this study show that the rs10046 (C/T) polymorphism of
      CYP19A1 gene exhibits correlation with CAD and that patients with C allele have
      an increased probability of manifesting the disease. 

PMID- 25861480
TI  - Factors driving readmissions in tibia and femur fractures.
AB  - As the American healthcare system shifts towards bundled payments, readmissions
      will become a measure of healthcare quality. The purpose of this study was to
      characterize readmission trends and factors influencing readmission in patients
      with diaphyseal femur and tibia fractures. Through a retrospective chart review,
      all patients who presented to a level 1 trauma center from 2004 to 2006 were
      evaluated. By using current procedural terminology codes, 1,040 patients with
      diaphyseal tibia or femur fractures fixed by IMN were identified. 645 patients
      were included for analysis. 30-day, 60-day, and 90-day readmission rates were
      compared with fracture type, reason for readmission, and basic demographic
      information. The 60-day readmission rate for open tibia fractures (14.8%) was
      significantly higher than the 60-day readmission rate for closed tibia fractures
      (8.0%) (p = 0.037). When comparing reasons for 60-day readmissions, 50% of closed
      fractures were readmitted due to infection, while the other 50% needed additional
      surgery. 91.7% of open fractures readmitted in 60 days were due to infection. In
      a bundled payment system, orthopedic trauma must gain insight into drivers of
      readmission to identify those at risk for readmission and design effective
      healthcare plans for these patients. 

PMID- 25861481
TI  - Full anatomical recovery of the dopaminergic system after a complete spinal cord
      injury in lampreys.
AB  - Following a spinal injury, lampreys at first are paralyzed below the level of
      transection. However, they recover locomotion after several weeks, and this is
      accompanied by the regeneration of descending axons from the brain and the
      production of new neurons in the spinal cord. Here, we aimed to analyse the
      changes in the dopaminergic system of the sea lamprey after a complete spinal
      transection by studying the changes in dopaminergic cell numbers and dopaminergic
      innervation in the spinal cord. Changes in the expression of the D2 receptor were
      also studied. We report the full anatomical regeneration of the dopaminergic
      system after an initial decrease in the number of dopaminergic cells and fibres.
      Numbers of dopaminergic cells were recovered rostrally and caudally to the site
      of injury. Quantification of dopaminergic profiles revealed the full recovery of
      the dopaminergic innervation of the spinal cord rostral and caudal to the site of
      injury. Interestingly, no changes in the expression of the D2 receptor were
      observed at time points in which a reduced dopaminergic innervation of the spinal
      cord was observed. Our observations reveal that in lampreys a spinal cord injury
      is followed by the full anatomical recovery of the dopaminergic system. 

PMID- 25861482
TI  - Successful perioperative management of a patient with the left ventricular assist
      device for brain tumor resection: case report and review of the literature.
AB  - Heart failure is the leading cause of death in the United States. Our
      increasingly aged population will contribute to an increased incidence and
      prevalence of heart failure, thereby augmenting the need for mechanical
      circulatory devices. Here we present the first successful resection of a brain
      tumor in a left ventricular device- (LVAD-) dependent patient with increased
      intracranial pressure and address pertinent perioperative anesthetic
      considerations and management. 

PMID- 25861483
TI  - Acute ventricular wall thickening: sepsis, thrombotic microangiopathy, or
      myocarditis?
AB  - Background. Acute myocardial oedema has been documented in experimental models of
      ischemia-reperfusion injury or sepsis and is usually investigated by magnetic
      resonance imaging. Purpose. We describe a case of acute ventricular wall
      thickening documented by echocardiography in a patient developing sepsis and
      thrombotic microangiopathy. Case Description. A 40-year-old woman, with a history
      of mixed connective tissue disease, was admitted with laryngeal oedema and fever.
      She developed Streptococcus pneumoniae septicaemia and subsequent laboratory
      abnormalities were consistent with a thrombotic microangiopathy. Echocardiography
      revealed an impressive diffuse thickening of the whole myocardium
      (interventricular septum 18 mm; posterior wall 16 mm) with diffuse hypokinesia
      and markedly reduced left ventricular ejection fraction (31%). There was also a
      moderate pericardial effusion. Echocardiography was normal two months before. The
      patient died from acute heart failure. Macroscopic and microscopic examination of
      the heart suggested that the ventricular wall thickening was induced by
      oedematous changes, together with an excess of inflammatory cells. Conclusion.
      Acute ventricular wall thickening that corresponded to myocardial oedema as a
      first hypothesis was observed at echocardiography during the course of
      septicaemia complicated by thrombotic microangiopathy. 

PMID- 25861484
TI  - Complete heart block with diastolic heart failure and pulmonary edema secondary
      to enlarging previously diagnosed thrombosed aneurysm of sinus of valsalva in a
      patient with history of autosomal dominant polycystic kidney disease.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is associated with vascular
      aneurysms that can affect any part of the vascular tree, like ascending aorta or
      coronary arteries. Sinus of Valsalva is known as an anatomical dilation at the
      root of aorta above the aortic valve and very few cases show aneurysm at that
      site in patients with ADPKD. Sinus of Valsalva aneurysm (SVA) can present with
      rupture and acute heart failure and infective endocarditis or could be
      asymptomatic accidentally discovered during cardiac catheterization. We report a
      case of a 76-year-old male with a unique constellation of cardiovascular
      anomalies associated with ADPKD. Patient was previously diagnosed with aneurysms
      affecting ascending aorta, sinus of Valsalva, and coronary arteries. Several
      years later, he came with complete heart block which was discovered later to be
      secondary to enlargement of his previously diagnosed thrombosed SVA. His case was
      complicated with acute heart failure and pulmonary edema. Conclusion. Patients
      with ADPKD can present with extrarenal manifestations. In our case, aneurysm at
      sinus of Valsalva was progressively enlarging and presented with complete heart
      block. 

PMID- 25861485
TI  - Peripheral giant cell granuloma associated with a dental implant: a case report
      and review of the literature.
AB  - The peripheral giant cell granuloma (PGCG) is a nonneoplastic lesion commonly
      caused by local irritation. This report describes a 46-year-old Caucasian male
      who presented with a PGCG associated with a dental implant. The dental implant
      was originally placed in August 2012. Ten months later, the patient presented
      with a well-circumscribed lesion associated with and covering the implant, at
      which time the lesion was excised. Four months later, due to recurrence of the
      lesion, a deeper and wider excisional biopsy with curettage of the adjacent bone
      was performed. No evidence of recurrence has been reported after 12 months of
      follow-up. Immunohistochemistry, using the antibody CD68, was performed to
      investigate the origin of the multinucleated giant cells, with their
      immunophenotype being similar to those of other giant cell lesions, including
      central giant cell granuloma, foreign-body reactions, and granulomatous reactions
      to infectious agents. 

PMID- 25861486
TI  - Effective and Efficient Herbst Appliance Therapy for Skeletal Class II
      Malocclusion Patient with a Low Degree of Collaboration with the Orthodontic
      Treatment.
AB  - The current concept for effective and efficient treatment of skeletal Class II
      malocclusion prescribes that interceptive approach should be delivered during the
      pubertal growth stage. However, psychosocial issues and a greater risk of dental
      trauma are also factors that should be addressed when considering early Class II
      therapy. This paper reports a case of a patient that sought orthodontic treatment
      due to aesthetic discomfort with the incisors' protrusion. Two previous
      treatments failed because patient's collaboration with removable appliances was
      inadequate. Given his history of no collaboration and because the patient was in
      the prepubertal stage, it was decided to try a different approach in the third
      attempt of treatment. Traumatic injury protective devices were used during the
      prepubertal stage and followed by Herbst appliance and fixed multibrackets
      therapy during the pubertal stage, resulting in an adequate outcome and long-term
      stability. 

PMID- 25861487
TI  - Two Basal cell carcinomas of the axillae: a metastasis or an independent
      development?
AB  - Cutaneous basal cell carcinoma (BCC) is a common malignancy amongst the elderly.
      BCC rarely metastasises, and fewer than 300 cases of metastatic BCC have been
      reported in the literature. Here, we report a case of sequentially developed BCCs
      located adjacent to each other. We discuss that these BCCs were considered to
      have developed independently rather than due to metastasis, after referencing
      previous studies on metastatic BCC. 

PMID- 25861488
TI  - P-chloroaniline poisoning causing methemoglobinemia: a case report and review of
      the literature.
AB  - Background. Methemoglobin (MetHb) most commonly results from exposure to an
      oxidizing chemical but may also arise from genetic, dietary, or even idiopathic
      etiologies. P-chloroaniline (PCA) was one of the first substances described in
      the context of acquired methemoglobinemia. Case Report. We report the case of a
      cyanotic chemistry worker who presented to our emergency department (ED) after
      working with PCA. His peripheral oxygen saturation (SpO2) measured by pulse
      oximetry was at 81% and remained on that level despite oxygen administration
      (100% oxygenation via nonrebreather mask). His MetHb level was measured at 42.8%
      in arterial blood gas analysis. After treatment with intravenous methylene blue
      cyanosis resolved and the patient was discharged after 36 hours of observation.
      Conclusion. Acquired methemoglobinemia is a treatable condition, which may cause
      significant morbidity and mortality. The knowledge about the most common causes,
      fast diagnostic, and proper treatment is crucial. 

PMID- 25861489
TI  - Herbal weight loss pill overdose: sibutramine hidden in pepper pill.
AB  - Supposedly herbal weight loss pills are sold online and are widely used in the
      world. Some of these products are found to contain sibutramine by FDA and their
      sale is prohibited. We report a case of a female patient who presented to the
      emergency department after taking slimming pills. 17-year-old female patient
      presented to the emergency room with palpitations, dizziness, anxiety, and
      insomnia. She stated that she had taken 3 pills named La Jiao Shou Shen for
      slimming purposes during the day. Her vital signs revealed tachycardia. On her
      physical examination, she was restless, her oropharynx was dry, her pupils were
      mydriatic, and no other pathological findings were found. Sibutramine
      intoxication was suspected. She was given 5 mg IV diazepam for restlessness.
      After supportive therapy and observation in emergency department for 12 hours
      there were no complications and the patient was discharged home. Some herbal
      pills that are sold online for weight loss have sibutramine hidden as an active
      ingredient, and their sale is prohibited for this reason. For people who use
      herbal weight loss drugs, sibutramine excessive intake should be kept in mind at
      all times. 

PMID- 25861490
TI  - Postoperative megarectum in an adult patient with imperforate anus and
      rectourethral fistula.
AB  - This report presents a surgical case of postoperative megarectum in an adult
      patient with imperforate anus/anorectal malformations. A 71-year-old Japanese
      male presented with a mass in the lower abdomen which was 15 * 12 * 8 cm in
      diameter, edema in the right lower extremity, and frequent urination. He had
      undergone sigmoid loop colostomy for an imperforate anus as a newborn infant. At
      28 years of age, the sigmoid loop colostomy was changed to sigmoid divided
      colostomy in the left lower abdomen. Computed tomography revealed a large cystic
      mass in the lower abdomen. Retrograde urethrography indicated a rectourethral
      fistula and megarectum with stones. A small laparotomy incision was created in
      the right lower abdomen, and the wall of the megarectum was identified.
      Approximately 2,300 mL of gray muddy fluid was identified and drained. A mucous
      fistula of the upper rectum was created in the right lower abdomen. This is an
      extremely rare case of postoperative megarectum in an adult patient with an
      imperforate anus and rectourethral fistula. 

PMID- 25861491
TI  - A Novel PHEX Mutation in Japanese Patients with X-Linked Hypophosphatemic
      Rickets.
AB  - X-linked hypophosphatemic rickets (XLH) is a dominant inherited disorder
      characterized by renal phosphate wasting, aberrant vitamin D metabolism, and
      abnormal bone mineralization. Inactivating mutations in the gene encoding
      phosphate-regulating gene with homologies to endopeptidases on the X chromosome
      (PHEX) have been found to be associated with XLH. Here, we report a 16-year-old
      female patient affected by hypophosphatemic rickets. We evaluated her serum
      fibroblast growth factor 23 (FGF23) levels and conducted sequence analysis of the
      disease-associated genes of FGF23-related hypophosphatemic rickets: PHEX, FGF23,
      dentin matrix protein 1, and ectonucleotide pyrophosphatase/phosphodiesterase 1.
      She was diagnosed with XLH based on her clinical features and family history.
      Additionally, we observed elevated FGF23 levels and a novel PHEX exon 9 mutation
      (c.947G>T; p.Gly316Val) inherited from her father. Although bioinformatics showed
      that the mutation was neutral, Gly316 is perfectly conserved among humans, mice,
      and rats, and there were no mutations in other FGF23-related rickets genes,
      suggesting that in silico analysis is limited in determining mutation
      pathogenicity. In summary, we present a female patient and her father with XLH
      harboring a novel PHEX mutation that appears to be causative of disease.
      Measurement of FGF23 for hypophosphatemic patients is therefore useful for the
      diagnosis of FGF23-dependent hypophosphatemia. 

PMID- 25861492
TI  - Giant thyroid abscess related to postpartum Brucella infection.
AB  - Thyroid gland infection, although rare, may be a life threatening disease.
      Thyroid abscess, arising from acute suppurative thyroiditis (AST), is a rare
      clinic condition depending on widespread use of antibiotics. Infection may
      involve one or both lobes and abscess formation may not be apparent until late
      stage of the progress of illness. Thyroid left lobe is more often affected than
      the right one. Brucellosis, especially obvious in endemic areas, is a widely seen
      zoonosis around the world. Although brucella infection can affect many organs
      through various complications, thyroid gland infection is rare. We aimed to
      present ultrasonography (USG) and magnetic resonance images (MRI) of a case with
      an acute thyroiditis which rapidly developed and grew fast on the left half of
      the neck during the first postpartum month. As far as we know from literature
      reviewing, our case is the first case report of a thyroid abscess arising from
      brucella infection which is developed in first postpartum period with images of
      ultrasonography and MRI. 

PMID- 25861493
TI  - JC Virus PCR Detection Is Not Infallible: A Fulminant Case of Progressive
      Multifocal Leukoencephalopathy with False-Negative Cerebrospinal Fluid Studies
      despite Progressive Clinical Course and Radiological Findings.
AB  - We describe a case with a false-negative PCR-based analysis for JC virus in
      cerebrospinal fluid (CSF) in a patient with clinical and radiological findings
      suggestive of progressive multifocal leukoencephalopathy (PML) who was on chronic
      immunosuppressive therapy for rheumatoid arthritis. Our patient developed rapidly
      progressive global decline with clinical and radiographic findings suggestive of
      PML, but JC virus PCR in CSF was negative. The patient passed away 3 months from
      the onset of her neurological symptoms. Autopsy confirmed the diagnosis of PML
      with presence of JC-polyoma virus by immunohistochemical staining. This case
      highlights the potential of false-negative JC virus PCR in CSF when radiographic
      and clinical features are suggestive of "possible PML." We review the plausible
      causes of potential false-negative CSF results and suggest that when the clinical
      presentation is suspicious for PML repeat CSF analysis utilizing ultrasensitive
      PCR assay and subsequent brain biopsy should be considered if CSF remains
      negative. Additionally, appropriate exclusion of other neurologic conditions is
      essential. 

PMID- 25861494
TI  - Successful Conservative Management of a Dislocated IUD.
AB  - Background. Intrauterine contraceptive devices (IUDs) are widely utilized all
      over the world owing to their low cost and high efficacy. Uterine perforation is
      a rare complication that may occur at IUD insertion resulting in extrauterine
      location of the IUD. Traditionally, surgical removal of dislocated IUDs has been
      recommended. Case. A 68-year-old patient who had an IUD (Lippes loop) inserted 32
      years ago and whose routine examination incidentally revealed a dislocated IUD in
      the abdominal cavity. The patient remained asymptomatic during three years of
      follow-up and the IUD was left in place. Conclusion. Asymptomatic patients, whose
      vaginal examinations and ultrasonography or X-ray results reveal a dislocated
      IUD, may benefit from conservative management. 

PMID- 25861495
TI  - Uterine balloon tamponade in combination with topical administration of
      tranexamic Acid for management of postpartum hemorrhage.
AB  - While uterine balloon tamponade is an effective modality for control of
      postpartum hemorrhage, the reported success rates have ranged from the level of
      60% to the level of 80%. In unsuccessful cases, more invasive interventions are
      needed, including hysterectomy as a last resort. We developed a modified
      tamponade method and applied it to two cases of refractory postpartum hemorrhage
      after vaginal delivery. The first case was accompanied by uterine myoma and low
      lying placenta. After an induced delivery, the patient had excessive hemorrhage
      due to uterine atony. Despite oxytocin infusion and bimanual uterine compression,
      the total blood loss was estimated at 2,800 mL or more. The second case was
      diagnosed as placental abruption complicated by fetal death and severe
      disseminated intravascular coagulation, subsequently. A profuse hemorrhage
      continued despite administration of uterotonics, fluid, and blood transfusion.
      The total blood loss was more than 5,000 mL. In each case, an intrauterine
      balloon catheter was wrapped in gauze impregnated with tranexamic acid, inserted
      into the uterus, and inflated sufficiently with sterile water. In this way,
      mechanical compression by a balloon and a topical antifibrinolytic agent were
      combined together. This method brought complete hemostasis and no further
      treatments were needed. Both the women left hospital in stable condition. 

PMID- 25861496
TI  - Maintenance Therapy Containing Metformin and/or Zyflamend for Advanced Prostate
      Cancer: A Case Series.
AB  - Metformin is derived from galegine, a natural ingredient, and recent studies have
      suggested that metformin could enhance the antitumor effects of hormone ablative
      therapy or chemotherapy and reduce prostate cancer-specific mortality. Zyflamend
      is a combination of herbal extracts that reduces inflammation and comprises
      turmeric, holy basil, green tea, oregano, ginger, rosemary, Chinese goldthread,
      hu zhang, barberry, and basil skullcap. We propose a maintenance regimen with
      metformin and/or Zyflamend that targets cancer stem cells and the tumor
      microenvironment to keep the cancer dormant and prevent it from activation from
      dormancy. Herein, we report the clinical course of four patients who experienced
      a clinical response after treatment with metformin and/or Zyflamend. 

PMID- 25861497
TI  - A Second New Choroidal Osteoma in the Same Eye: Differences between Them with New
      Imaging Techniques.
AB  - The authors introduce a 42-year-old woman with a choroidal osteoma. After 10
      years the patient presented a second choroidal osteoma in the same eye; this
      osteoma has been growing in the last years. New tests that were unavailable
      during the first diagnosis were performed such as Fundus Autofluorescence or
      Enhanced Depth Imaging-Optical Coherence Tomography (EDI-OCT). These tests show
      characteristics of the tumors and allow us to realize a visual prognosis for the
      patient. 

PMID- 25861498
TI  - Idiopathic organ transplant chorioretinopathy after liver transplantation.
AB  - Idiopathic organ transplant chorioretinopathy is a rare disease associated with
      kidney and heart transplantation. We present a case secondary to liver
      transplantation including its multimodal imaging, differential diagnosis, and
      physiopathology discussion. 

PMID- 25861499
TI  - A symptomatic spinal extradural arachnoid cyst with lumbar disc herniation.
AB  - Spinal epidural arachnoid cyst (EAC) is a rare, usually asymptomatic condition of
      unknown origin, which typically involves the lower thoracic spine. We report a
      case of posttraumatic symptomatic EAC with lumbar disc herniation. A 22-year-old
      man experienced back pain and sciatica after a traffic accident. Neurological
      examination revealed a right L5 radiculopathy. Magnetic resonance imaging
      demonstrated a cystic lesion at the L3 to L5 level and an L4-5 disc herniation;
      computed tomography myelography showed that the right L5 root was sandwiched
      between the cyst and the herniation. A dural defect was identified during
      surgery. The cyst was excised completely and the defect was repaired. A
      herniation was excised beside the dural sac. Histology showed that the cyst wall
      consisted of collagen and meningothelial cells. Postoperatively the symptoms
      resolved. Lumbar spinal EACs are rare; such cysts may arise from a congenital
      dural crack and grow gradually. The 6 cases of symptomatic lumbar EAC reported in
      the literature were not associated with disc herniation or trauma. In this case,
      the comorbid disc herniation was involved in symptom progression. Although many
      EACs are asymptomatic, comorbid spinal disorders such as disc herniation or
      trauma can result in symptom progression. 

PMID- 25861500
TI  - Synovial chondromatosis of the subacromial bursa causing a bursal-sided rotator
      cuff tear.
AB  - Synovial chondromatosis is an uncommon condition, and involvement of the shoulder
      is even more rare. We report on a 39-year-old female who presented with symptoms,
      radiographic features, and intraoperative findings consistent with multiple
      subacromial loose bodies resulting in a partial-thickness, bursal-sided rotator
      cuff tear of the supraspinatus muscle. She was treated with an arthroscopic
      removal of loose bodies, complete excision of the subacromial/subdeltoid bursa,
      acromioplasty, and rotator cuff repair. To our knowledge, this is the first
      report of arthroscopic treatment for a bursal-sided, partial-thickness rotator
      cuff tear treated with greater than two-year clinical and radiographic follow-up.
      We utilized shoulder scores, preoperative and postoperative range of motion, and
      imaging to assess the results of treatment and surveillance for recurrence in our
      patient after two-year follow-up. 

PMID- 25861501
TI  - Irreducible fifth metatarsophalangeal joint after car crush injury.
AB  - Metatarsophalangeal joint dislocations are uncommon injuries. Herein, an
      irreducible dislocation of fifth metatarsophalangeal joint with fractures on the
      second, third, and fourth metatarsal head was reported. Joint reduction could not
      be achieved which necessitated open reduction. Six months after surgery the
      patient was walking and doing his daily activities without any complaints. He had
      returned to his pretrauma functional level. 

PMID- 25861502
TI  - Extravasation mucocele arising from a lingual thyroglossal duct remnant.
AB  - Although a thyroglossal duct cyst is a congenital anomaly, it can also appear in
      adults. Despite the presence of embryological remnants, it is still unclear why
      the cyst should suddenly develop later in life. We report a case of a 46-year-old
      male with an extravasation mucocele arising from a long-standing lingual
      thyroglossal duct remnant. MRI demonstrated a lingual cystic lesion near the
      hyoid bone associated with a suprahyoid tract-like structure masquerading as a
      thyroglossal duct cyst. However, histopathological examination demonstrated a
      mucocele secondary to a rupture of a thyroglossal duct remnant with numerous
      intramural heterotopic salivary glands. We propose a new mechanism of an acquired
      cystic formation of this congenital disease that excessive production of mucus
      from heterotopic salivary glands and a physical trauma such as swallowing may
      lead to extravasation of mucus from the thyroglossal duct. 

PMID- 25861503
TI  - Adult-onset woakes' syndrome: report of a rare case.
AB  - Introduction. Woakes' syndrome, commonly defined as severe recurrent nasal polyps
      with consecutive destruction of the nasal pyramid, is rare with only a few
      reports in the literature documenting surgical treatment of the external nose.
      Case Presentation. We describe the case of an adult patient with Samter's triad
      who had been surgically treated from nasal polyposis since 2002. By 2014 a
      conspicuous deformity of the nasal pyramid had progressively occurred due to a
      recurrence. The patient underwent revision endoscopic sinus surgery and narrowing
      of the bony nasal vault by digital compression without osteotomies. Discussion.
      Having been described over 130 years ago, the etiology of Woakes' syndrome
      remains poorly understood. Treatment includes endoscopic sinus surgery and
      topical treatment. Surgical treatment of the external nose deformity by
      rhinoplasty is rarely addressed. Conclusion. This case illustrates that the
      widening of the bony nasal vault may be successfully corrected by digital
      compression, if the nasal bones are substantially thinned, in combination with
      surgical treatment of nasal polyps. 

PMID- 25861504
TI  - Ameloblastic fibrosarcoma of the mandible: a case report and brief review of the
      literature.
AB  - Ameloblastic fibrosarcoma is an uncommon odontogenic tumor composed of a benign
      epithelial component and a malignant ectomesenchymal component most frequently
      seen in the third and fourth decades of life. It mainly presents as a painful
      maxillary or mandibular swelling. Radiographs show a radiolucent mass with ill
      defined borders. Radical surgical excision and long-term follow-up are the
      suggested treatment. We report the case of a 22-year-old female with a 2-month
      history of an asymptomatic swelling in her left mandible. Examination revealed an
      exophytic growth measuring 3 * 3 cm extending from the mandibular left first
      premolar to the second molar. The patient underwent a left hemimandibular
      resection. Histopathological examination revealed a biphasic tumor composed of
      inconspicuous islands of benign odontogenic epithelium and an abundant malignant
      mesenchymal component with marked cellularity, nuclear pleomorphism,
      hyperchromatism, and moderate mitotic figures with clear margins; one year after
      the surgical procedure, the patient is clinically and radiologically disease
      free. 

PMID- 25861505
TI  - Therapeutic Hypothermia and Out-of-Hospital Cardiac Arrest in a Child with
      Hypertrophic Obstructive Cardiomyopathy.
AB  - Neurologic outcomes following pediatric cardiac arrest are consistently poor.
      Early initiation of cardiopulmonary resuscitation has been shown to have positive
      effects on both survival to hospital discharge, and improved neurological
      outcomes after cardiac arrest. Additionally, the use of therapeutic hypothermia
      may improve survival in pediatric cardiac arrest patients admitted to the
      intensive care unit. We report a child with congenital hypertrophic obstructive
      cardiomyopathy and an out-of-hospital cardiac arrest, in whom the early
      initiation of effective prolonged cardiopulmonary resuscitation and subsequent
      administration of therapeutic hypothermia contributed to a positive outcome with
      no gross neurologic sequelae. Continuing efforts should be made to promote and
      employ high-quality cardiopulmonary resuscitation, which likely contributed to
      the positive outcome of this case. Further research will be necessary to develop
      and solidify national guidelines for the implementation of therapeutic
      hypothermia in selected subpopulations of children with OHCA. 

PMID- 25861506
TI  - Lung cancer with skin and breast metastasis: a case report and literature review.
AB  - Lung cancer is one of the most common cancers in America. Frequent sites of
      metastasis include the Hilar lymph nodes, adrenal glands, liver, brain, and bone.
      The following case report is of a primary lung cancer with metastases to the
      breast and skin. Case. A 48-year-old African American male with a past medical
      history of poorly differentiated left breast cancer status after modified radical
      mastectomy (MRM), chronic obstructive pulmonary disease, and smoking (20 pack
      years) presents to the ER with progressive shortness of breath on exertion, upper
      back pain, and weight loss for 2 months in duration. On physical examination he
      is found to have a MRM scar on his left breast and a left periumbilical cutaneous
      mass. Chest X-ray and chest CT reveal a right upper lobe mass and biopsies from
      the breast, lung, and the periumbilical mass indicate a poorly differentiated
      carcinoma of unclear etiology; all tumor markers are negative. The patient is
      male and a chronic smoker; therefore the diagnosis is made as lung carcinoma with
      metastases to the breast and skin. Conclusion. A high index of suspicion for
      cutaneous metastases should be cast when investigating cutaneous pathologies in
      patients at risk for primary lung malignancy. 

PMID- 25861507
TI  - Rapid pituitary apoplexy regression: what is the time course of clot resolution?
AB  - A 29-year-old male patient with a functioning pituitary macroadenoma is
      discussed. The pituitary mass was detected by MRI after the patient presented
      with sudden onset of headache, suggestive of an apoplectic event. The headache
      resolved with analgesic medications. Within a follow-up period of one week, the
      pituitary mass had spontaneously regressed to nearly half its original size
      without any therapy. The patient never reported any visual complaints and
      displayed no signs of hypopituitarism. Elevated prolactin levels were present.
      Seven weeks after the initial event, the pituitary mass showed continued
      regression on MRI. Prolactin levels remained elevated. This case provides a
      unique look at the rapid spontaneous regression of mass effect that may occur
      following apoplexy of a pituitary adenoma. 

PMID- 25861508
TI  - Hyperplastic cardiac sarcoma recurrence.
AB  - Primary cardiac sarcomas are rare tumors with a median survival of 6-12 months.
      Data suggest that an aggressive multidisciplinary approach may improve patient
      outcome. We present the case of a male who underwent resection of cardiac sarcoma
      three times from the age of 32 to 34. This report discusses the malignant nature
      of cardiac sarcoma and the importance of postoperative multidisciplinary care. 

PMID- 25861509
TI  - Surgical resection for a second primary lung cancer originating close to the
      initial surgical margin for lung squamous cell carcinoma.
AB  - Few reports have described surgical resection for second primary lung cancers
      originating close to the initial surgical margin for lung cancer. A 64-year-old
      man had undergone left segmentectomy with lymph node dissection for small
      peripheral squamous cell lung cancer using video-assisted thoracic surgery, with
      pathology confirming a small tumor 12 mm in diameter identified about 3 cm from
      the surgical margin. Eighteen months after initial surgery, computed tomography
      revealed a 30 mm pulmonary nodule close to the initial surgical margin in the
      residual left upper lobe and the serum level of carcinoembryonic antigen was
      found to be increased. Local recurrence on the staple-line of the surgical margin
      was suspected, and completion left upper lobectomy was performed. Histological
      examination identified not only a squamous cell carcinoma component but also a
      small cell carcinoma component. The immunohistochemical staining pattern of the
      second tumor differed from that of the initial resected lung squamous cell
      carcinoma. The final pathological diagnosis was a second primary tumor with mixed
      small cell carcinoma and squamous cell carcinoma histology. 

PMID- 25861510
TI  - A rare cause of colonic obstruction "colonic intussusception": report of two
      cases.
AB  - Colocolic intussusceptions are rare clinical entities in adults and almost always
      caused by a leading lesion which often warrants resection. Mostly being
      malignant, the leading lesions are rarely benign lesions where intraluminal
      lipomas are the most frequent among them. Most adult intussusceptions require
      surgical resection owing to two major reasons: common presence of a leading
      lesion and significantly high risk of malignancy-reaching as high as 65%
      regardless of the anatomic site-of the leading lesion. Resection of the affected
      segment is usually the treatment of choice, since preoperative diagnosis of the
      lesion is usually ineffective and most leading lesions are malignant. This paper
      represents two cases of adult colocolic intussusception caused by intraluminal
      lipomas with a brief review of the literature. 

PMID- 25861511
TI  - Single-Incision Laparoscopic Surgery for Undiagnosed Small Bowel Obstruction in a
      Patient without a History of Abdominal Surgery.
AB  - We herein report a 66-year-old female patient who developed an undiagnosed small
      bowel obstruction without a history of prior abdominal surgery and was
      successfully treated by single-incision laparoscopic surgery. A small bowel
      obstruction with unknown cause typically requires some sort of surgical treatment
      in parallel with a definitive diagnosis. Although open abdominal surgery has been
      generally performed for the treatment of small bowel obstructions, laparoscopic
      surgery for small bowel obstructions has been increasing in popularity due to its
      less invasiveness, including fewer postoperative complications and a shorter
      hospital stay. As a much less invasive therapeutic strategy, we have performed
      single-incision laparoscopic surgery for the treatment of an undiagnosed small
      bowel obstruction. We were able to make a definitive diagnosis after sufficient
      intra-abdominal inspection and to perform enterotomy through a small umbilical
      incision. Single-incision laparoscopic surgery appears to be comparable to
      conventional laparoscopic surgery and provides improved cosmesis, although it is
      an optional strategy only applicable to selected patients. 

PMID- 25861512
TI  - Utilization of Intraoperative TEE to Assess Supraventricular Tachycardia-Inducing
      Right-Sided Cardiac Compression by the Liver, Post-Liver-Transplantation Status.
AB  - This unique and interesting case report involves a patient who recently underwent
      a combined liver and kidney transplant (due to autosomal dominant polycystic
      kidney disease) and subsequently suffered from episodes of supraventricular
      tachycardia (SVT) secondary to the new liver graft compressing the right atrium
      and ventricle. After this was diagnosed, the patient underwent operative
      plication of the right hemidiaphragm. Intraoperative transesophageal
      echocardiography was used to demonstrate cardiac compression from the liver and
      demonstrate resolution of compression after plication of the hemidiaphragm. 

PMID- 25861513
TI  - Transurethral incision of the bladder neck in a woman with primary bladder neck
      obstruction after kidney transplantation.
AB  - Voiding dysfunction is frequently seen in the early posttransplant period. Among
      other causes, this condition can arise due to bladder outlet obstruction. Primary
      bladder neck obstruction (PBNO) is a possible but very rare cause of bladder
      outlet obstruction. We present the case of a 52-year-old woman who, after kidney
      transplantation, presented with PBNO. The diagnosis was established based on
      symptoms, uroflowmetry, and multichannel urodynamics with electromyography. The
      transurethral incision of the bladder neck was made at the 5- and 7-o'clock
      position. After the operation, the maximal flow rate was significantly increased,
      and postvoid residual urine was decreased compared to the preoperative findings.
      The patient was followed for 5 years, and her voiding improvement is persistent.
      This is the first reported case of PBNO treated with a transurethral incision of
      the bladder neck in a posttransplantation female patient. 

PMID- 25861514
TI  - Torsion of a large appendix testis misdiagnosed as pyocele.
AB  - Torsion of the appendix testis is not an uncommon cause of acute hemiscrotum. It
      is frequently misdiagnosed as acute epididymitis, orchitis, or torsion of testis.
      Though conservative management is the treatment of choice for this condition,
      prompt surgical intervention is warranted when testicular torsion is suspected.
      We report a case of torsion of a large appendix testis misdiagnosed as pyocele.
      Emergency exploration of it revealed a large appendix testis with torsion and
      early features of gangrene. After excision of the appendix testis, the wound was
      closed with an open drain. The patient had an uneventful and smooth postoperative
      recovery. 

PMID- 25861515
TI  - Recurrence of prostate cancer with cutaneous metastasis after radical
      prostatectomy.
AB  - While cutaneous metastases are already extremely rare in primary metastatic
      prostatic adenocarcinoma, cutaneous manifestations in recurrent prostate cancer
      have rarely been described prior to this report. Here we present the case report
      of a 93-year-old male who underwent radical prostatectomy but eventually suffered
      from a previously undescribed recurrence of prostatic adenocarcinoma with distant
      cutaneous metastases to proximal right lower leg. 

PMID- 25861516
TI  - Determination of propranolol hydrochloride in pharmaceutical preparations using
      near infrared spectrometry with fiber optic probe and multivariate calibration
      methods.
AB  - A method for determination of propranolol hydrochloride in pharmaceutical
      preparation using near infrared spectrometry with fiber optic probe (FTNIR/PROBE)
      and combined with chemometric methods was developed. Calibration models were
      developed using two variable selection models: interval partial least squares
      (iPLS) and synergy interval partial least squares (siPLS). The treatments based
      on the mean centered data and multiplicative scatter correction (MSC) were
      selected for models construction. A root mean square error of prediction (RMSEP)
      of 8.2 mg g(-1) was achieved using siPLS (s2i20PLS) algorithm with spectra
      divided into 20 intervals and combination of 2 intervals (8501 to 8801 and 5201
      to 5501 cm(-1)). Results obtained by the proposed method were compared with those
      using the pharmacopoeia reference method and significant difference was not
      observed. Therefore, proposed method allowed a fast, precise, and accurate
      determination of propranolol hydrochloride in pharmaceutical preparations.
      Furthermore, it is possible to carry out on-line analysis of this active
      principle in pharmaceutical formulations with use of fiber optic probe. 

PMID- 25861517
TI  - Current status and scope of lymph node micrometastasis in gastric cancer.
AB  - Recently, lymph node micrometastasis has been evaluated for its prognostic value
      in gastric cancer. Lymph node micrometastasis cannot be detected via a usual
      pathologic examination, but it can be detected by using some other techniques
      including immunohistochemistry and reverse transcription-polymerase chain
      reaction assay. With the development of such diagnostic techniques, the detection
      rate of lymph node micrometastasis is constantly increasing. Although the
      prognostic value of lymph node micrometastasis remains debatable, its clinical
      impact is apparently remarkable in both early and advanced gastric cancer. At
      present, studies on the prognostic value of lymph node micrometastasis are
      evolving to overcome its current limitations and extend the scope of its
      application. 

PMID- 25861518
TI  - Comparison of international guidelines on the accompanying therapy for advanced
      gastric cancer: reasons for the differences.
AB  - The purpose of this study was to determine if international guidelines differ in
      their recommendations concerning additive therapy for advanced, but potentially
      curable, gastric cancer. A systematic search of the English and German literature
      was conducted in the databases Medline, Cochrane Database, Embase, and PubMed.
      The search terms used were 'guidelines gastric cancer,' 'guidelines stomach
      cancer,' and 'Leitlinien Magenkarzinom.' Six different guidelines published after
      January 1, 2010, in which the tumors were classified according to the seventh
      edition of the TNM system (2010), were identified. Although the examined
      guidelines were based on the same study results, their recommendations concerning
      accompanying therapy for gastric cancer differ considerably. While perioperative
      chemotherapy is recommended in Germany, Great Britain, and large parts of Europe,
      postoperative adjuvant radiochemotherapy or perioperative chemotherapy is
      recommended in the USA and Canada. In Japan, postoperative adjuvant chemotherapy
      is recommended.The results of identical studies were interpreted differently in
      different countries. Since considerable effort is required for each country to
      separately test relevant studies for their validity and suitability, an
      international cooperation could simplify the creation of a common basis for
      guidelines and contribute to improved comparability of international guidelines. 

PMID- 25861519
TI  - Significant differences in the clinicopathological characteristics and survival
      of gastric cancer patients from two cancer centers in china and Korea.
AB  - PURPOSE: To compare the clinicopathological data and long-term survival of
      gastric cancer patients in China and Korea. MATERIALS AND METHODS: Patients who
      had undergone gastrectomy for gastric cancer between 1998 and 2009 in 2 high
      volume institutions in both China (n=1,637) and Korea (n=2,231) were
      retrospectively evaluated. Clinicopathological variables, overall survival (OS),
      progression-free survival (PFS), and surgery-related complications were assessed
      for all patients and compared between the 2 institutions. RESULTS: Chinese
      patients included in the study were significantly older and had a significantly
      lower body mass index (BMI) than the Korean patients. Esophagogastric junction
      tumors were more frequent in Chinese patients. However, the number of patients
      with stage I gastric cancer, the number of harvested lymph nodes, and the number
      of total gastrectomies were significantly higher in the Korean population. Korean
      patients also presented with fewer undifferentiated tumors than Chinese patients.
      Furthermore, Korean patients had prolonged OS and PFS for stage III cancers only.
      BMI, tumor-node-metastasis (TNM) stage, tumor invasion, number of positive lymph
      nodes, and distant metastases were all independent factors affecting OS and PFS.
      CONCLUSIONS: Although China and Korea are neighboring Asian countries, the
      clinicopathological characteristics of Chinese patients are significantly
      different from those of Korean patients. Korean gastric cancer patients had
      longer OS and PFS than Chinese patients. Influencing factors included TNM stage,
      tumor invasion, and lymph node metastasis.

PMID- 25861520
TI  - Lessons learned from a comparative analysis of surgical outcomes of and learning
      curves for laparoscopy-assisted distal gastrectomy.
AB  - PURPOSE: Before expanding our indications for laparoscopic gastrectomy to
      advanced gastric cancer and adopting reduced port laparoscopic gastrectomy, we
      analyzed and audited the outcomes of laparoscopy-assisted distal gastrectomy
      (LADG) for adenocarcinoma; this was done during the adoptive period at our
      institution through the comparative analysis of short-term surgical outcomes and
      learning curves (LCs) of two surgeons with different careers. MATERIALS AND
      METHODS: A detailed comparative analysis of the LCs and surgical outcomes was
      done for the respective first 95 and 111 LADGs performed by two surgeons between
      July, 2006 and June, 2011. The LCs were fitted by using the non-linear ordinary
      least squares estimation method. RESULTS: The postoperative morbidity and
      mortality rates were 14.6% and 0.0%, respectively, and there was no significant
      difference in the morbidity rates (12.6% vs. 16.2%, P=0.467). More than 25 lymph
      nodes were retrieved by each surgeon during LADG procedures. The LCs of both
      surgeons were distinct. In this study, a stable plateau of the LC was not
      achieved by both surgeons even after performing 90 LADGs. CONCLUSIONS: Regardless
      of the experience with gastrectomy or laparoscopic surgery for other organs, or
      the age of surgeon, the outcome was quite acceptable; the learning process differ
      according to the surgeon's experience and individual characteristics.

PMID- 25861521
TI  - Loss of FAT Atypical Cadherin 4 Expression Is Associated with High Pathologic T
      Stage in Radically Resected Gastric Cancer.
AB  - PURPOSE: Recent studies have revealed recurrent alterations in the cell adhesion
      gene FAT4, a candidate tumor suppressor gene, in cancer. FAT atypical cadherin 4
      (FAT4) is a transmembrane receptor involved in the Hippo signaling pathway, which
      is involved in the control of organ size. Here, we investigated the loss of FAT4
      expression and its association with clinicopathological risk factors in gastric
      cancer. MATERIALS AND METHODS: We assessed the expression of FAT4 by using
      immunohistochemistry on three tissue microarrays containing samples from 136
      gastric cancer cases, radically resected in the Soonchunhyang University Cheonan
      Hospital between July 2006 and June 2008. Cytoplasmic immunoexpression of FAT4
      was semi-quantitatively scored using the H-score system. An H-score of >=10 was
      considered positive for FAT4 expression. RESULTS: Variable cytoplasmic
      expressions of FAT4 were observed in gastric cancers, with 33 cases (24.3%)
      showing loss of expression (H-score <10). Loss of FAT4 expression was associated
      with an increased rate of perineural invasion (H-score <10 vs. >=10, 36.4% vs.
      16.5%, P=0.015), high pathologic T stage (P=0.015), high tumor-node-metastasis
      stage (P=0.017), and reduced disease-free survival time (H-score <10 vs. >=10,
      mean survival 62.7+/-7.3 months vs. 79.1+/-3.1 months, P=0.025). However, no
      association was found between the loss of FAT4 expression and tumor size, gross
      type, histologic subtype, Lauren classification, lymphovascular invasion, or
      overall survival. CONCLUSIONS: Loss of FAT4 expression appears to be associated
      with invasiveness in gastric cancer.

PMID- 25861522
TI  - A comparison of outcomes of three reconstruction methods after laparoscopic
      distal gastrectomy.
AB  - PURPOSE: The aim of this study was to compare the short-term surgical and long
      term functional outcomes of Billroth I, Billroth II, and Roux-en-Y reconstruction
      after laparoscopic distal gastrectomy. MATERIALS AND METHODS: We retrospectively
      collected data from 697 patients who underwent laparoscopic distal gastrectomy
      for operable gastric cancer between January 2009 and December 2012. The patients
      were classified into three groups according to the reconstruction methods:
      Billroth I, Billroth II, and Roux-en-Y. The parameters evaluated included patient
      and tumor characteristics, operative details, and postoperative complications
      classified according to the Clavien-Dindo classification. Endoscopic findings of
      the remnant stomach were evaluated according to the residue, gastritis, bile
      (RGB) classification and the Los Angeles classification 1 year postoperatively.
      RESULTS: Billroth I, Billroth II, and Roux-en-Y were performed in 165 (23.7%),
      371 (53.2%), and 161 patients (23.1%), respectively. Operation time was
      significantly shorter (173.4+/-44.7 minute, P<0.001) as was time to first flatus
      (2.8+/-0.8 days, P=0.009), time to first soft diet was significantly faster
      (4.3+/-1.0 days, P<0.001), and postoperative hospital stay was significantly
      shorter (7.7+/-4.0 days, P=0.004) in Billroth I in comparison to the other
      methods. Postoperative complications higher than Clavien-Dindo grade III occurred
      in 61 patients (8.8%) with no statistically significant differences between
      groups (P=0.797). Endoscopic findings confirmed that gastric residue, gastritis,
      bile reflux, and reflux esophagitis were significantly lower in Roux-en-Y
      (P<0.001) patients. CONCLUSIONS: Roux-en-Y reconstruction after laparoscopic
      distal gastrectomy for middle-third gastric cancer is beneficial in terms of long
      term functional outcome, whereas Billroth I reconstruction for distal-third
      gastric cancer has a superior short-term surgical outcome and postoperative
      weight change.

PMID- 25861523
TI  - Setting the stomach transection line based on anatomical landmarks in
      laparoscopic distal gastrectomy.
AB  - Laparoscopic distal gastrectomy has become widespread as a treatment for early
      gastric cancer in eastern Asia, but a standard method for setting the stomach
      transection line has not been established. Here we report a novel method of
      setting this line based on anatomical landmarks. At the start of the operation,
      two anatomical landmarks along the greater curvature of the stomach were marked
      with ink: the proximal landmark at the avascular area between the last branch of
      the short gastric artery and the first branch of the left gastroepiploic artery,
      and the distal landmark at the point of communication between the right and left
      gastroepiploic arteries. Just before specimen retrieval, the stomach was
      transected from the center of these two landmarks toward the lesser curvature.
      Then, about two-third of the stomach was reproducibly resected, and
      gastroduodenostomy was successfully performed in 26 consecutive cases. This novel
      method could be used as a standard technique for setting the transection line in
      laparoscopic distal gastrectomy. 

PMID- 25861524
TI  - Gastric duplication cysts in adults: a report of three cases.
AB  - Gastric duplication cyst is a rare congenital anomaly of the gastrointestinal
      tract and is especially uncommon in adults. Most cases in adults are discovered
      incidentally on radiological examination or gastric endoscopy. Accurate diagnosis
      of these cysts before resection is difficult. Differential diagnoses are varied.
      Malignant transformation of a gastric duplication cyst is very rare. We present
      three cases of asymptomatic noncommunicating gastric duplication cysts in adults.

PMID- 25861525
TI  - Inflammatory myofibroblastic tumor treated with laparoscopic proximal gastrectomy
      and double-tract anastomosis.
AB  - Inflammatory myofibroblastic tumors (IMTs) of the stomach are extremely rare in
      adults, and their oncologic prognosis is not well understood. We present a 28
      year-old man with a proximal gastric IMT. The patient visited the emergency
      department of Yeouido St. Mary's Hospital with syncope and hematemesis.
      Hemoglobin levels were <5.5 g/dl. Gastric fibroscopy showed a protruding mass 4*4
      cm in size, with central ulceration on the posterior wall of the fundus and
      diffuse wall thickening throughout the cardia and anterior wall of the upper
      body. Endoscopic biopsy revealed indeterminate spindle cells, along with
      inflammation. Given the risk of rebleeding, an operation was performed despite
      the uncertain diagnosis. Because the mass was circumferential, laparoscopic
      proximal gastrectomy and double-tract anastomosis were performed to ensure a safe
      resection margin. The pathological diagnosis was consistent with an IMT
      originating from the stomach, although the tumor was negative for anaplastic
      lymphoma kinase gene mutation. 

PMID- 25861526
TI  - Two cases of advanced gastric carcinoma mimicking a malignant gastrointestinal
      stromal tumor.
AB  - Gastric cancer that mimics a submucosal tumor is rare. This rarity and the normal
      mucosa covering the protuberant tumor make it difficult to diagnosis with
      endoscopy. We report two cases of advanced gastric cancer that mimicked malignant
      gastrointestinal stromal tumors preoperatively. In both cases, the possibility of
      cancer was not completely ruled out. In the first case, a large tumor was
      suspected to be cancerous during surgery. Therefore, total gastrectomy with lymph
      node dissection was performed. In the second case, the first gross endoscopic
      finding was of a Borrmann type II advanced gastric cancer-like protruding mass
      with two ulcerous lesions invading the anterior wall of the body. Therefore,
      subtotal gastrectomy with lymph node dissection was performed. Consequently,
      delayed treatment of cancer was avoided in both cases. If differential diagnosis
      between malignant gastrointestinal stromal tumor and cancer is uncertain, a
      surgical approach should be carefully considered due to the possible risk of
      adenocarcinoma. 

PMID- 25861528
TI  - Is a long term work in automotive industry a risk factor for renal dysfunction?
AB  - BACKGROUND: Disorders of renal system can cause renal failure; therefore
      screening is necessary especially in workers who are exposed to harmful
      materials. Hypertension, diabetes mellitus, and hazardous exposures are non
      occupational and occupational risk factors for renal diseases. AIM: The objective
      of this study was to determine the effects of working in automotive industry on
      renal function in Iran. SUBJECTS AND METHODS: In a historical cohort study,
      workers of automotive industry who worked in production and had low exposure to
      metal fumes were selected and divided to three groups with 5-10, 11-20, and 21-30
      years work duration. risk factors for renal diseases were collected and analyzed
      with SPSS using one-way ANOVA, correlation coefficient and with P < 0.05 and
      relative risk with a confidence interval (CI). RESULTS: The means of work
      duration in Groups (A), (B) and (C) were 9.8 (0.6), 13.8 (2.0), 22.3 (1.6) years
      respectively with ANOVA (F) =187.864 and P < 0.01. Glomerular filtration rate
      (GFR) was 59.75 (0.70), 59.16 (1.52) and 59.10 (2.23) in Groups (A), (B), and (C)
      respectfully The relative risk of creatinine clearance, uric acid and mean blood
      pressure were the highest in Group (B); 1.970 - CI, 0.541-7.169, 1.571 95% CI:
      0.198-12.470, and 1.519 95% CI: 0.425-5.426, but the differences were not
      significant. CONCLUSION: GFRs were decreased with work duration, but the
      differences were not significant. Working in automotive Industry with low
      exposure to toxic metals and solvents has no significant effect on GFR,
      creatinine clearance, uric acid, and mean blood pressure.

PMID- 25861527
TI  - Anticancer Effect of AntiMalarial Artemisinin Compounds.
AB  - The anti-malarial drug artemisinin has shown anticancer activity in vitro and
      animal experiments, but experience in human cancer is scarce. However, the
      ability of artemisinins to kill cancer cells through a variety of molecular
      mechanisms has been explored. A PubMed search of about 127 papers on anti-cancer
      effects of antimalarials has revealed that this class of drug, including other
      antimalarials, have several biological characteristics that include anticancer
      properties. Experimental evidences suggest that artemisinin compounds may be a
      therapeutic alternative in highly aggressive cancers with rapid dissemination,
      without developing drug resistance. They also exhibit synergism with other
      anticancer drugs with no increased toxicity toward normal cells. It has been
      found that semisynthetic artemisinin derivatives have much higher antitumor
      activity than their monomeric counterparts via mechanisms like apoptosis, arrest
      of cell cycle at G0/G1, and oxidative stress. The exact mechanism of activation
      and molecular basis of these anticancer effects are not fully elucidated.
      Artemisinins seem to regulate key factors such as nuclear factor-kappa B,
      survivin, NOXA, hypoxia-inducible factor-1alpha, and BMI-1, involving multiple
      pathways that may affect drug response, drug interactions, drug resistance, and
      associated parameters upon normal cells. Newer synthetic artemisinins have been
      developed showing substantial antineoplastic activity, but there is still limited
      information regarding the mode of action of these synthetic compounds. In view of
      the emerging data, specific interactions with established chemotherapy need to be
      further investigated in different cancer cells and their phenotypes and validated
      further using different semisynthetic and synthetic artemisinin derivatives. 

PMID- 25861529
TI  - Actualities of management of aural, nasal, and throat foreign bodies.
AB  - BACKGROUND: Foreign bodies (Fbs) in the ear, nose, and throat (ENT) are common
      presentations in healthcare settings worldwide. AIM: This study was carried out
      to review the modes of presentation, management, and outcome of inserted Fbs in
      our setting. SUBJECTS AND METHODS: A 5-year retrospective study of cases of ENT
      Fbs managed at two referral hospitals in Abuja Nigeria. The analysis was done
      with Chi-square and Pearson correlation. RESULTS: Five hundred and ninety-four
      patients aged 0-75 years, M:F = 1.1 (295 vs. 299) were reviewed. Prevalence was
      predominantly among the under 5 s; 286/594 (P = 0.001). ENT Fbs were 356/594
      (59.9%), 167/594 (28.1%) and 71/59 (12.0%), respectively. Cotton wool 133/356
      (37.4%) and beads 75/356 (21.1%) constituted most aural Fbs. Beads 45/167 (27.0%)
      and grains/seed 37/167 (22.1%) were the most common nasal Fbs while fish bones
      38/71 (53.5%) and piece of metals 12/71 (16.9%) were dominant in the throat. Most
      cases of aural and nasal Fbs were asymptomatic. Ear syringing was the most common
      method for removal of aural Fbs 216/594 (60.7%) and instrumentation under direct
      vision for nasal Fbs 153/167 (91.6%). Furthermore, 52/71 (73.2%) of throat Fbs
      were removed under general anesthesia. ENT complications observed included
      bruises, lacerations, perforations, Epistaxis, and a case of respiratory failure.
      Delayed presentation (beyond 24 h) was seen in 489/594 (82.3%) of cases while
      failed previous attempts by untrained hands constituted 353/594 (59.4%). A strong
      correlation between complications and duration of Fbs insertion (R (2) = 0.8759)
      was established. CONCLUSIONS: Fbs in ENT are common especially among children
      below 5 years. Majority presented beyond 24 h, and there was a strong correlation
      between duration of Fbs insertion and associated complications. Repeated failed
      attempts and delayed referrals to otorhinolaryngologists from peripheral centers
      were also contributing factors to increased morbidity and hence the need for
      awareness.

PMID- 25861530
TI  - Quantification and localization of mast cells in periapical lesions.
AB  - BACKGROUND: Periapical lesions occur in response to chronic irritation in
      periapical tissue, generally resulting from an infected root canal. Specific
      etiological agents of induction, participating cell population and growth factors
      associated with maintenance and resolution of periapical lesions are incompletely
      understood. Among the cells found in periapical lesions, mast cells have been
      implicated in the inflammatory mechanism. AIM: Quantifications and the possible
      role played by mast cells in the periapical granuloma and radicular cyst. Hence,
      this study is to emphasize the presence (localization) and quantification of mast
      cells in periapical granuloma and radicular cyst. MATERIALS AND METHODS: A total
      of 30 cases and out of which 15 of periapical granuloma and 15 radicular cyst,
      each along with the case details from the previously diagnosed cases in the
      department of oral pathology were selected for the study. The gender distribution
      showed male 8 (53.3%) and females 7 (46.7%) in periapical granuloma cases and
      male 10 (66.7%) and females 5 (33.3%) in radicular cyst cases. The statistical
      analysis used was unpaired t-test. RESULTS: Mean mast cell count in periapical
      granuloma subepithelial and deeper connective tissue, was 12.40 (0.99%) and 7.13
      (0.83%), respectively. The mean mast cell counts in subepithelial and deeper
      connective tissue of radicular cyst were 17.64 (1.59%) and 12.06 (1.33%)
      respectively, which was statistically significant. No statistical significant
      difference was noted among males and females. CONCLUSION: Mast cells were more in
      number in radicular cyst. Based on the concept that mast cells play a critical
      role in the induction of inflammation, it is logical to use therapeutic agents to
      alter mast cell function and secretion, to thwart inflammation at its earliest
      phases. These findings may suggest the possible role of mast cells in the
      pathogenesis of periapical lesions.

PMID- 25861531
TI  - Cytokeratin 19 expression patterns of dentigerous cysts and odontogenic
      keratocysts.
AB  - BACKGROUND: Although numerous investigators have studied the pattern of keratin
      expression in different odontogenic cysts, the results have been variable. AIM:
      The present study was conducted to determine the pattern of expression of
      cytokeratin 19 (CK 19) in the epithelial lining of odontogenic keratocysts and
      dentigerous cysts. MATERIALS AND METHODS: The epithelial layers showing
      expression of the epithelial marker CK 19 was determined by immunohistochemical
      methods in 15 tissue specimens each of histopathologically confirmed cases of
      dentigerous cysts and odontogenic keratocysts. Statistical analysis was done to
      compare the CK 19 expression between dentigerous cyst and odontogenic keratocyst
      using the Chi-square test. P < 0.05 was considered to be statistically
      significant. RESULTS: All specimens of dentigerous cysts were positive for CK 19
      with 20% (3/15) of the specimens showing expression only in a single layer of the
      epithelium, 40% (6/15) of the specimens showing expression in more than one layer
      but not the entire thickness of the epithelium, and the remaining 40% (6/15)
      showing expression throughout the entire thickness of the epithelium. In the case
      of odontogenic keratocysts, 40% (6/15) of the specimens were negative for CK 19,
      40% (6/15) of the specimens showed expression only in a single layer of the
      epithelium, and 20% (3/15) of the specimens showed expression in more than one
      layer, but not the entire thickness of the epithelium. The observed differences
      in CK 19 expression by the two lesions were statistically significant (P < 0.01).
      CONCLUSION: The differences in CK 19 expression by these cysts may be utilized as
      a diagnostic tool in differentiating between these two lesions.

PMID- 25861532
TI  - Observations on the current bacteriological profile of chronic suppurative otitis
      media in South eastern Nigeria.
AB  - BACKGROUND: Chronic suppurative otitis media (CSOM) is a disease well-known for
      its recurrence and persistence despite treatment. The situation is compounded by
      the increasing resistance to antimicrobial agents by bacteria these days. AIM:
      This study was carried out to examine the current local bacteriological profile
      of CSOM and to compare the profile of either ear in bilaterally discharging ears.
      MATERIALS AND METHODS: We carried out a retrospective analysis of ear swab
      cultures from 133 unilateral and 73 bilateral consecutive tubotympanic CSOM cases
      seen at the Ear-Nose-Throat clinics of a referral health institution during a 4
      year period ending 2013. Sensitivities to eight locally available antibiotics
      were analyzed. Aerobic bacterial isolates were analyzed separately for the
      unilateral and bilateral cases. Comparison was made between the ears in the
      bilateral cases. RESULTS: We analyzed 279 ear swab culture results from 206
      patients with age ranging from 5 months to 86 years and a mean of 21.3 (19.5)
      years. Pseudomonas aeruginosa was the most common isolated bacteria (44%
      [109/250]) followed by Staphylococcus aureus (17% [42/250]), and Proteus
      Mirabilis (15% [38/250]). The most and least sensitive bacteria were Klebsiella
      Spp and Escherichia Coli, respectively. The most effective antibiotics were
      gentamicin and ciprofloxacin. The two ears differ significantly in the rates of
      isolation of S. aureus and E. coli (P = 0.01 and P = 0.04, respectively).
      CONCLUSION: Pseudomonas is the most common bacteria involved in CSOM in this part
      of the country. Ciprofloxacin as ear drops is recommended as first-line drug in
      the management of active CSOM as it is cheap, less ototoxic, and locally
      available. Separate ear swab culture should be obtained in bilateral CSOM.

PMID- 25861533
TI  - Seasonal variation in exposure level of types a and B ultraviolet radiation: an
      environmental skin carcinogen.
AB  - BACKGROUND: The main source of ultraviolet radiation (UVR) is the sun, affecting
      organs such as the skin, eyes, and immune system. According to American
      Conference of Governmental Industrial Hygienist (ACGIH) reports, the amount of
      UVR reaching the Earth's surface is increasing yearly and is responsible for an
      increase in solar radiation-related diseases. AIMS: To investigate the amount of
      UVR reaching the Earth's surface and understand the risk of UVR on disease among
      outdoor laborers in one of the central provinces of Iran. MATERIALS AND METHODS:
      Arak city was divided into two geographic areas, and the weekly measurement of
      UVR was done in three locations) asphalt, grass and rooftop). To measure UVR,
      Hanger UV spectrometer, standard deviation (SD8-A), and SD8-B detectors were
      used. Amounts of UVR for a consecutive year and varying weather conditions were
      measured. Finally, values obtained were compared to ACGIH standards. RESULTS: The
      minimum and maximum levels of UV type A radiation occurred in April 1.27 (0.724)
      W/m(2) and September 7.147 (4.128) W/m(2), these figures for UV type B were in
      March-April 0.005 (0.003) and September 0.083 (0.077). The maximum UVR is
      received between 11 and 15 o'clock. CONCLUSIONS: In the central cities of Iran,
      the minimum and maximum UV type A and B is received in March-April and in
      September, respectively. Based on the results, the angular position of the sun in
      the sky, cloud cover, and height from ground level affected the amount of UVR
      received, but the geographic locations studied did not.

PMID- 25861534
TI  - An alternative instrument for making entry point for elastic intramedullary nail.
AB  - Femoral shaft fractures are common in children and are increasingly being treated
      with elastic intramedullary nail. We outline an instrument we have used
      successfully to make an entry point for placement of elastic nail. 

PMID- 25861535
TI  - A rare case report of spontaneous resolution of hepatic portal venous gas
      associated with cocaine-induced intestinal ischemia.
AB  - Hepatic portal venous gas (HPVG) is a rare disease entity. It is an ominous
      finding, usually, associated with intraabdominal ischemic necrosis. It frequently
      requires emergent surgical intervention. Herein, we present a case of a patient
      who complained of intense abdominal pain, with radiographic findings of HPVG as a
      result of cocaine-induced vascular insufficiency. After 5 h of nonoperative and
      conservative management, the HPVG spontaneously resolved. The patient clinically
      improved and was discharged home in a stable condition. 

PMID- 25861536
TI  - Isolated penile degloving from milling machine injury in a child.
AB  - Degloving injuries of the male perineum are an uncommon urological emergency
      often requiring reconstruction. They are usually related to industrial and/or
      agricultural machinery and tend to involve both the penile shaft and the scrotal
      skin. Adolescents and young adults are the usual victims. The treatment options
      commonly employed include the use of the degloved skin either as a flap or more
      often as a free skin graft, yielding variable results. Other modalities include
      the use of free split skin grafts or free full thickness skin grafts (FTSG)
      (Wolfe grafts). We report a case of degloving injury in a 10-year-old child, with
      injury exclusively affecting the skin of the penile shaft, who presented in the
      sub-acute phase. Optimization of the wound and subsequent cover of the defect
      with an FTSG yielded a good outcome and patient satisfaction. 

PMID- 25861537
TI  - Conservative management of twisted ischemic adnexa in early pregnancy.
AB  - Diagnosis of adnexal torsion can be difficult, especially during pregnancy. Delay
      in diagnosis can lead to necrosis and loss of the affected ovary compromising the
      reproductive capacity, especially in young women. A 22-year-old primigravida
      presented to the emergency room at 10 weeks of gestation with acute onset left
      iliac fossa pain. Ultrasound examination showed a live intra-uterine gestation of
      10 weeks, enlarged and edematous left ovary with a clear cyst of 76 mm * 63 mm
      with flow to the ovary. She underwent emergency surgery with a provisional
      diagnosis of torsion of left adnexa. Mini-laparotomy, detorsion of the twisted
      adnexa and ovarian cystectomy with reconstruction was performed thus conserving
      the tube and ovary. The pregnancy progressed normally; follow-up ultrasound scans
      showed normal functioning ovaries. Clinical appearance of torted adnexa does not
      correlate well with the residual function. Ovarian function can be preserved by
      untwisting, even if ovary appears necrotic. 

PMID- 25861538
TI  - Central diabetes insipidus, central hypothyroidism, renal tubular acidosis and
      dandy-walker syndrome: new associations.
AB  - Dandy-Walker syndrome (DWS) is a rare brain malformation involving the
      cerebellum, and the fluid filled spaces around it, usually detected during the
      antenatal period or the early infancy. Clinically, it is characterized by mental
      retardation, developmental delay as well as cerebellar ataxia. It has been
      frequently associated with other conditions such as congenital heart diseases,
      primary hypothyroidism, and other disorders of the central nervous,
      gastrointestinal, genitourinary, and orthopedic systems. In this report, we
      describe a 3-month-old Saudi boy with the rare association of DWS with central
      diabetes insipidus, congenital central hypothyroidism, and type-2 renal tubular
      acidosis. 

PMID- 25861539
TI  - Myomectomy for retained placenta due to incarcerated fibroid mass.
AB  - Retained placenta is one of the most common complications of preterm delivery
      and/or mid-trimester miscarriage. It is an important cause of increased maternal
      morbidity and sometimes mortality especially in developing countries. It is
      associated with several complications that could be tasking to the facility and
      of great challenge to the obstetrician. Here we present a very rare event in
      obstetrics which is retained placenta due to incarcerated, posteriorly-sited
      fibroid that was successfully managed with myomectomy. 

PMID- 25861540
TI  - Amalgam contact hypersensitivity lesion: an unusual presentation-report of a rare
      case.

PMID- 25861541
TI  - Immunization dropout rates: some issues.

PMID- 25861542
TI  - Erratum: Debating Elective Single Embryo Transfer after in vitro Fertilization: A
      Plea for a Context Sensitive Approach: Erratum.
AB  - [This corrects the article on p. 1 in vol. 5, PMID: 25745568.]. 

PMID- 25861543
TI  - Twin reversed arterial perfusion sequence: a rare entity.
AB  - Twin reversed arterial perfusion (TRAP) sequence is an extremely rare
      complication of monochorionic multi-fetal pregnancy, occurring once in 35,000
      births. This condition is characterized by a malformed fetus without a cardiac
      pump being perfused by a structurally normal (pump) twin via an artery-to-artery
      anastomosis in a reverse direction. We report a case of a primigravida, who came
      for routine antenatal checkup to our hospital at 31 weeks gestational age.
      Ultrasound imaging and magnetic resonance imaging revealed twin monochorionic
      intrauterine pregnancy with a viable, normal-appearing first twin and amorphous
      structured second twin connected by umbilical vessels. The patient was monitored
      with weekly ultrasonography, echocardiography, and Doppler ultrasound examination
      to ascertain the well-being of the pump twin. She delivered successfully at term
      a normal live baby and an acardius acephalus fetus. Plain X-ray of the acardius
      acephalus fetus confirmed the absence of cephalic structures. The perinatal
      mortality of the pump twin ranges from 35 to 55%; hence, it is essential to
      diagnose the presence of a pump twin at an early gestational age through improved
      imaging techniques, so that intervention can be planned early in the pregnancy
      for a better outcome of the pump twin. 

PMID- 25861544
TI  - Complete currarino syndrome recognized in adulthood.
AB  - Currarino syndrome is a hereditary pathology that is characterized by
      sacrococcygeal bone defect, presacral mass, and anorectal malformation.
      Sacrococcygeal bone defect is almost always a part of the syndrome. The complete
      form of this entity displays all three abnormalities and is very uncommon. In
      this report, we present the magnetic resonance imaging findings of a case with
      complete form of Currarino syndrome recognized in adulthood. 

PMID- 25861545
TI  - Role of advanced MRI brain sequences in diagnosing neurological complications of
      scrub typhus.
AB  - Scrub typhus is a rare disease affecting many organs and causing vasculitis by
      affecting the endothelium of blood vessels. Review of literature shows that there
      are only a few case reports describing the neuroradiological manifestations of
      scrub typhus. This case report describes how newer and advanced MRI sequences are
      able to diagnose neurological complications of scrub typhus, such as hemorrhages,
      meningoencephalitis, infarctions, cranial nerve involvement, thrombosis, and
      hypoperfusion, that are not picked up on routine magnetic resonance imaging (MRI)
      sequences. 

PMID- 25861546
TI  - Congenital absence of the right pericardium: embryology and imaging.
AB  - Though congenital pericardial absence is often asymptomatic, complications can be
      life threatening. To date, few short case reports, primarily from the pre-CT and
      MR era, describe congenital absence of the right pericardium. We present a more
      comprehensive discussion of the embryologic derangements causing such defects and
      offer an up-to-date review of characteristic radiologic findings. Recognition of
      characteristic imaging findings of congenital pericardial absence is crucial in
      guiding diagnosis and management. 

PMID- 25861547
TI  - Malignant tenosynovial giant cell tumor of the leg: a radiologic-pathologic
      correlation and review of the literature.
AB  - Malignant tenosynovial giant cell tumor (TGCT) is a rare clinical entity that can
      arise as a recurrent lesion or can co-exist with a benign TGCT lesion. Malignant
      TGCT most commonly arises in the lower extremity and tends to be clinically
      aggressive, with most patients developing recurrent lesions or dying. Much of the
      literature describes the histopathologic features and classifies this broad group
      of tumors, with little description of the imaging characteristics of this
      disease. We present the multimodality appearance of a case of malignant diffuse
      type TGCT that recurred 2 months after resection with subsequent rapid clinical
      progression. 

PMID- 25861548
TI  - Mechanical Thrombectomy with Rotarex System in Buerger's Disease.
AB  - We report the case of a patient with 2-month history of chronic thromboembolism
      of the distal superficial femoral and popliteal arteries with diagnostic features
      of thromboangiitis obliterans disease. The occlusion could not be crossed by
      antegrade approach and was achieved retrogradely via dorsalis pedis artery
      puncture followed by mechanical removal of the thrombus with Rotarex system
      (Straub Medical AG, Wangs, Switzerland). Subsequent ballooon angioplasties
      achieved exclusion of the thrombus, and straight-line flow established to the
      foot through the anterior tibial Artery. The present case report demonstrates the
      success of mechanical thrombectomy in a patient with Buerger's vasculitis. 

PMID- 25861549
TI  - Isolated asymptomatic metastasis in the myocardium: a rare scenario in case of
      carcinoma penis.
AB  - Penile cancer is a common malignancy in developing countries. It commonly
      metastasizes to the lymph nodes, lung, liver, and bones. Myocardial metastasis is
      rare. A 40-year-old male patient presented with ulcerative growth over glans
      penis. Histologic evaluation of the biopsy sample diagnosed the lesion as
      squamous cell cancer. Assessment of the stage of the disease revealed cardiac
      metastasis. Patient received six cycles of chemotherapy. He partially responded,
      but later succumbed to cardiac failure due to pericardial and pleural effusion. 

PMID- 25861550
TI  - Wassel's Type V Polydactyly with Plain Radiographic and CT Findings.
AB  - Duplication of the thumb is the most common polydactyly of the hand. Wassel's
      classification is frequently used to classify the polydactyly of the hand. His
      classification was based on the level of duplication and the number of bones in
      the thumb, and has seven groups (Types I-VII) according to the level of the
      bifurcation, except for his Type VII. The most common type is the bifurcation at
      the metacarpophalangeal joint (Type IV). In this paper, we report a very rare
      case of Type V thumb polydactyly in a 42-year-old man, who presented with swan
      neck deformity of the radial thumb and discuss the plain radiography and computed
      tomography (CT) findings. Kumar recently reported plain radiography findings in a
      case of bifid first metacarpal in a 13-year-old girl, who presented with swan
      neck deformity of the left thumb. To our knowledge, our case is the second
      presented case that has a swan neck deformity with bifid metacarpal. 

PMID- 25861551
TI  - Wormhole Hamiltonian Monte Carlo.
AB  - In machine learning and statistics, probabilistic inference involving multimodal
      distributions is quite difficult. This is especially true in high dimensional
      problems, where most existing algorithms cannot easily move from one mode to
      another. To address this issue, we propose a novel Bayesian inference approach
      based on Markov Chain Monte Carlo. Our method can effectively sample from
      multimodal distributions, especially when the dimension is high and the modes are
      isolated. To this end, it exploits and modifies the Riemannian geometric
      properties of the target distribution to create wormholes connecting modes in
      order to facilitate moving between them. Further, our proposed method uses the
      regeneration technique in order to adapt the algorithm by identifying new modes
      and updating the network of wormholes without affecting the stationary
      distribution. To find new modes, as opposed to redis-covering those previously
      identified, we employ a novel mode searching algorithm that explores a residual
      energy function obtained by subtracting an approximate Gaussian mixture density
      (based on previously discovered modes) from the target density function.

PMID- 25861553
TI  - Self-regulatory mode (locomotion and assessment), well-being (subjective and
      psychological), and exercise behavior (frequency and intensity) in relation to
      high school pupils' academic achievement.
AB  - Background. Self-regulation is the procedure implemented by an individual
      striving to reach a goal and consists of two inter-related strategies: assessment
      and locomotion. Moreover, both subjective and psychological well-being along
      exercise behaviour might also play a role on adolescents academic achievement.
      Method. Participants were 160 Swedish high school pupils (111 boys and 49 girls)
      with an age mean of 17.74 (sd = 1.29). We used the Regulatory Mode Questionnaire
      to measure self-regulation strategies (i.e., locomotion and assessment). Well
      being was measured using Ryff's Psychological Well-Being Scales short version,
      the Temporal Satisfaction with Life Scale, and the Positive Affect and Negative
      Affect Schedule. Exercise behaviour was self-reported using questions pertaining
      to frequency and intensity of exercise compliance. Academic achievement was
      operationalized through the pupils' mean value of final grades in Swedish,
      Mathematics, English, and Physical Education. Both correlation and regressions
      analyses were conducted. Results. Academic achievement was positively related to
      assessment, well-being, and frequent/intensive exercise behaviour. Assessment
      was, however, negatively related to well-being. Locomotion on the other hand was
      positively associated to well-being and also to exercise behaviour. Conclusions.
      The results suggest a dual (in)direct model to increase pupils' academic
      achievement and well-being-assessment being directly related to higher academic
      achievement, while locomotion is related to frequently exercising and well-being,
      which in turn, increase academic achievement. 

PMID- 25861554
TI  - Effect of different heterotrophic plate count methods on the estimation of the
      composition of the culturable microbial community.
AB  - Heterotrophic plate counts (HPC) are routinely determined within the scope of
      water quality assessment. However, variable HPC methods with different
      cultivation parameters (i.e., temperature and media type) are applied, which
      could lead to significant effects in the outcome of the analysis. Therefore the
      effect of different HPC methods, according to DIN EN ISO 6222 and EPA, on the
      culturable microbial community composition was investigated by 16S rRNA gene
      sequence analysis and statistical evaluation was performed. The culturable
      community composition revealed significant effects assigned to temperature (p <
      0.01), while for media type no statistical significance was observed. However,
      the abundance of certain detected bacteria was affected. Lower temperature (22 
      degrees C) showed the abundance of naturally occurring Pseudomonadaceae and
      Aeromonadaceae, whereas at high temperature (37  degrees C) numerous
      Enterobacteriaceae, Citrobacter spp. and Bacilli were identified. The highest
      biodiversity was detected at lower temperature, especially on R2A medium. These
      results indicate that different temperatures (low and high) should be included
      into HPC measurement and selection of media should, ideally, be adjusted to the
      monitored water source. Accordingly, it can be inferred that the HPC method is
      more suitable for continuous monitoring of the same water source than for single
      assessments of a water sample. 

PMID- 25861555
TI  - The right whale mandatory ship reporting system: a retrospective.
AB  - In 1998, the United States sought and received International Maritime
      Organization-endorsement of two Mandatory Ship Reporting (MSR) systems designed
      to improve mariner awareness about averting ship collisions with the endangered
      North Atlantic right whale (Eubalaena glacialis). Vessel collisions are a serious
      threat to the right whale and the program was among the first formal attempts to
      reduce this threat. Under the provisions of the MSR, all ships >300 gross tons
      are required to report their location, speed, and destination to a shore-based
      station when entering two key right whale habitats: one in waters off New England
      and one off coastal Georgia and Florida. In return, reporting ships receive an
      automatically-generated message, delivered directly to the ship's bridge, that
      provides information about right whale vulnerability to vessel collisions and
      actions mariners can take to avoid collisions. The MSR has been in operation
      continuously from July 1999 to the present. Archived incoming reports provided a
      15-plus year history of ship operations in these two locations. We analyzed a
      total of 26,772 incoming MSR messages logged between July 1999 and December 2013.
      Most ships that were required to report did so, and compliance rates were
      generally constant throughout the study period. Self-reported vessel speeds when
      entering the systems indicated that most ships travelled between 10 and 16 (range
      = 5-20 +) knots. Ship speeds generally decreased in 2009 to 2013 following
      implementation of vessel speed restrictions. The number of reports into the
      southern system remained relatively constant following a steady increase through
      2007, but numbers in the northern system decreased annually beginning in 2008. If
      reporting is indicative of long-term patterns in shipping operations, it reflects
      noteworthy changes in marine transportation. Observed declines in ship traffic
      are likely attributable to the 2008-2009 economic recession, the containerized
      shipping industry making increased use of larger ships that made fewer trips, and
      diminished oil/gas US imports as previously inaccessible domestic deposits were
      exploited. Recent declines in shipping activity likely resulted in lowered
      collision risks for right whales and reduced their exposure to underwater noise
      from ships. 

PMID- 25861556
TI  - Psychosocial interventions for adults with visible differences: a systematic
      review.
AB  - Background. Some individuals with visible differences have been found to
      experience psychosocial adjustment problems that can lead to social anxiety and
      isolation. Various models of psychosocial intervention have been used to reduce
      social anxiety and appearance related distress in this population. The objective
      of this review was to update a previous systematic review assessing the efficacy
      of psychosocial intervention programs for adults with visible differences. The
      original review (Bessell & Moss, 2007) identified 12 papers for inclusion.
      Methods. A search protocol identified studies from 13 electronic journal
      databases. METHODS: Studies were selected in accordance with pre-set inclusion
      criteria and relevant data were extracted. Results. This update identified an
      additional four papers that met the inclusion criteria. Two papers provided very
      limited evidence for the efficacy of a combined cognitive-behavioural and social
      skills training approach. None of the papers provided sufficient evidence for the
      optimal duration, intensity or setting of psychosocial interventions for this
      population. Discussion. The review concluded that a greater number of Randomised
      Controlled Trials and experimental studies were required to increase the
      methodological validity of intervention studies.

PMID- 25861557
TI  - Proteomic responses to hypoxia at different temperatures in the great scallop
      (Pecten maximus).
AB  - Hypoxia and hyperthermia are two connected consequences of the ongoing global
      change and constitute major threats for coastal marine organisms. In the present
      study, we used a proteomic approach to characterize the changes induced by
      hypoxia in the great scallop, Pecten maximus, subjected to three different
      temperatures (10  degrees C, 18  degrees C and 25  degrees C). We did not observe
      any significant change induced by hypoxia in animals acclimated at 10  degrees C.
      At 18  degrees C and 25  degrees C, 16 and 11 protein spots were differentially
      accumulated between normoxia and hypoxia, respectively. Moreover, biochemical
      data (octopine dehydrogenase activity and arginine assays) suggest that animals
      grown at 25  degrees C switched their metabolism towards anaerobic metabolism
      when exposed to both normoxia and hypoxia, suggesting that this temperature is
      out of the scallops' optimal thermal window. The 11 proteins identified with high
      confidence by mass spectrometry are involved in protein modifications and
      signaling (e.g., CK2, TBK1), energy metabolism (e.g., ENO3) or cytoskeleton
      (GSN), giving insights into the thermal-dependent response of scallops to
      hypoxia. 

PMID- 25861558
TI  - Conspicuous carotenoid-based pelvic spine ornament in three-spined stickleback
      populations-occurrence and inheritance.
AB  - Reports on reddish carotenoid-based ornaments in female three-spined sticklebacks
      (Gasterosteus aculeatus) are few, despite the large interest in the species'
      behaviour, ornamentation, morphology and evolution. We sampled sticklebacks from
      17 sites in north-western Europe in this first extensive study on the occurrence
      of carotenoid-based female pelvic spines and throat ornaments. The field results
      showed that females, and males, with reddish spines were found in all 17
      populations. Specimens of both sexes with conspicuous red spines were found in
      several of the sites. The pelvic spines of males were more intensely red compared
      to the females' spines, and large specimens were more red than small ones. Fish
      infected with the tapeworm (Schistocephalus solidus) had drabber spines than
      uninfected fish. Both sexes had red spines both during and after the spawning
      period, but the intensity of the red colour was more exaggerated during the
      spawning period. As opposed to pelvic spines, no sign of red colour at the throat
      was observed in any female from any of the 17 populations. A rearing experiment
      was carried out to estimate a potential genetic component of the pelvic spine
      ornament by artificial crossing and rearing of 15 family groups during a 12
      months period. The results indicated that the genetic component of the red colour
      at the spines was low or close to zero. Although reddish pelvic spines seem
      common in populations of stickleback, the potential adaptive function of the
      reddish pelvic spines remains largely unexplained. 

PMID- 25861559
TI  - Sloths like it hot: ambient temperature modulates food intake in the brown
      throated sloth (Bradypus variegatus).
AB  - Sloths are considered to have one of the lowest mass-specific metabolic rates of
      any mammal and, in tandem with a slow digestive rate, have been theorized to have
      correspondingly low rates of ingestion. Here, we show in a study conducted over
      five months, that three captive Bradypus variegatus (Brown-throated sloths) had a
      remarkably low mean food intake of 17 g kg(-1)day(-1) (SD 4.2). Food consumption
      was significantly affected by ambient temperature, with increased intake at
      higher temperatures. We suggest that the known fluctuation of sloth core body
      temperature with ambient temperature affects the rate at which gut fauna process
      digesta, allowing for increased rates of fermentation at higher temperatures.
      Since Bradypus sloths maintain a constantly full stomach, faster rates of
      fermentation should enhance digestive throughput, increasing the capacity for
      higher levels of food intake, thereby allowing increased energy acquisition at
      higher ambient temperatures. This contrasts with other mammals, which tend to
      show increased levels of food intake in colder conditions, and points to the
      importance of temperature in regulating all aspects of energy use in sloths. 

PMID- 25861560
TI  - The effects of set volume during isolated lumbar extension resistance training in
      recreationally trained males.
AB  - Background/Aim. Exercise designed to condition the lumbar extensor musculature is
      often included in resistance training (RT) programs. It is suggested that
      deconditioning of this musculature may be linked to low back pain. Thus effective
      means of conditioning these muscles are of interest to pursue. Evidence suggests
      that isolated lumbar extension (ILEX) RT might be most efficacious, however, the
      best means of manipulating resistance training variables in this regard is
      unknown. Set volume is an easily manipulated RT variable and one thought to also
      interact with training status. As such this study sought to examine the effect of
      set volume during ILEX RT in trained males. Methods. Trained males previously
      engaged in exercises designed to condition the lumbar extensors underwent a 6
      week intervention and were randomised to either a single set (1ST, n = 9),
      multiple set (3ST, n = 8) or control group (CON, n = 9). Pre- and post-testing of
      ILEX strength was conducted. Results. Both 1ST and 3ST significantly increased
      ILEX strength (p < 0.05) with large effect sizes (d = 0.89 and 0.95 respectively)
      whereas the CON group produced significant losses (-8.9%) with a moderate effect
      size (d = - 0.53). There was no statistically significant difference in ILEX
      strength gains when 1ST and 3ST were directly compared (p = 0.336). Conclusions.
      The results of this study suggest that significant ILEX strength changes occur in
      trained males as a result of 6 weeks of ILEX RT and that these changes are
      unaffected by set volume. 

PMID- 25861564
TI  - Open-access chemistry with impact.

PMID- 25861561
TI  - Genome evolution in an ancient bacteria-ant symbiosis: parallel gene loss among
      Blochmannia spanning the origin of the ant tribe Camponotini.
AB  - Stable associations between bacterial endosymbionts and insect hosts provide
      opportunities to explore genome evolution in the context of established
      mutualisms and assess the roles of selection and genetic drift across host
      lineages and habitats. Blochmannia, obligate endosymbionts of ants of the tribe
      Camponotini, have coevolved with their ant hosts for ~40 MY. To investigate early
      events in Blochmannia genome evolution across this ant host tribe, we sequenced
      Blochmannia from two divergent host lineages, Colobopsis obliquus and Polyrhachis
      turneri, and compared them with four published genomes from Blochmannia of
      Camponotus sensu stricto. Reconstructed gene content of the last common ancestor
      (LCA) of these six Blochmannia genomes is reduced (690 protein coding genes),
      consistent with rapid gene loss soon after establishment of the symbiosis.
      Differential gene loss among Blochmannia lineages has affected cellular functions
      and metabolic pathways, including DNA replication and repair, vitamin
      biosynthesis and membrane proteins. Blochmannia of P. turneri (i.e., B. turneri)
      encodes an intact DnaA chromosomal replication initiation protein, demonstrating
      that loss of dnaA was not essential for establishment of the symbiosis. Based on
      gene content, B. obliquus and B. turneri are unable to provision hosts with
      riboflavin. Of the six sequenced Blochmannia, B. obliquus is the earliest
      diverging lineage (i.e., the sister group of other Blochmannia sampled) and
      encodes the fewest protein-coding genes and the most pseudogenes. We identified
      55 genes involved in parallel gene loss, including glutamine synthetase, which
      may participate in nitrogen recycling. Pathways for biosynthesis of coenzyme A,
      terpenoids and riboflavin were lost in multiple lineages, suggesting relaxed
      selection on the pathway after inactivation of one component. Analysis of
      Illumina read datasets did not detect evidence of plasmids encoding missing
      functions, nor the presence of coresident symbionts other than Wolbachia.
      Although gene order is strictly conserved in four Blochmannia of Camponotus sensu
      stricto, comparisons with deeply divergent lineages revealed inversions in eight
      genomic regions, indicating ongoing recombination despite ancestral loss of recA.
      In sum, the addition of two Blochmannia genomes of divergent host lineages
      enables reconstruction of early events in evolution of this symbiosis and
      suggests that Blochmannia lineages may experience distinct, host-associated
      selective pressures. Understanding how evolutionary forces shape genome reduction
      in this system may help to clarify forces driving gene loss in other bacteria,
      including intracellular pathogens. 

PMID- 25861565
TI  - Reversible mechanical switching of magnetic interactions in a molecular shuttle.
AB  - An acid-base switchable molecular shuttle based on a [2]rotaxane, incorporating
      stable radical units in both the ring and dumbbell components, is reported. The
      [2]rotaxane comprises a dibenzo[24]crown-8 ring (DB24C8) interlocked with a
      dumbbell component that possesses a dialkylammonium (NH2 (+)) and a 4,4'
      bipyridinium (BPY(2+)) recognition site. Deprotonation of the rotaxane NH2 (+)
      centers effects a quantitative displacement of the DB24C8 macroring to the
      BPY(2+) recognition site, a process that can be reversed by acid treatment.
      Interaction between stable 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) radicals
      connected to the ring and dumbbell components could be switched between
      noncoupled (three-line electron paramagnetic resonance (EPR) spectrum) and
      coupled (five-line EPR spectrum) upon displacement of the spin-labelled DB24C8
      macroring. The complete base- and acid-induced switching cycle of the EPR pattern
      was repeated six times without an appreciable loss of signal, highlighting the
      reversibility of the process. Hence, this molecular machine is capable of
      switching on/off magnetic interactions by chemically driven reversible mechanical
      effects. A system of this kind represents an initial step towards a new
      generation of nanoscale magnetic switches that may be of interest for a variety
      of applications. 

PMID- 25861566
TI  - Anodic stripping voltammetry of silver nanoparticles: aggregation leads to
      incomplete stripping.
AB  - The influence of nanoparticle aggregation on anodic stripping voltammetry is
      reported. Dopamine-capped silver nanoparticles were chosen as a model system, and
      melamine was used to induce aggregation in the nanoparticles. Through the anodic
      stripping of the silver nanoparticles that were aggregated to different extents,
      it was found that the peak area of the oxidative signal corresponding to the
      stripping of silver to silver(I) ions decreases with increasing aggregation.
      Aggregation causes incomplete stripping of the silver nanoparticles. Two possible
      mechanisms of 'partial oxidation' and 'inactivation' of the nanoparticles are
      proposed to account for this finding. Aggregation effects must be considered when
      anodic stripping voltammetry is used for nanoparticle detection and
      quantification. Hence, drop casting, which is known to lead to aggregation, is
      not encouraged for preparing electrodes for analytical purposes. 

PMID- 25861567
TI  - The Necessity of Having a Tetradentate Ligand to Extract Copper(II) Ions from
      Amyloids.
AB  - The accumulation of redox-active metal ions, in particular copper, in amyloid
      plaques is considered to the cause of the intensive oxidation damage to the brain
      of patients with Alzheimers disease (AD). Drug candidates based on a bis(8
      aminoquinoline) tetradentate ligand are able to efficiently extract Cu(2+) from
      copper-loaded amyloids (Cu-Abeta). Contrarily, in the presence of a bidentate
      hydroxyquinoline, such as clioquinol, the copper is not released from Abeta, but
      remains sequestrated within a Abeta-Cu-clioquinol ternary complex that has been
      characterized by mass spectrometry. Facile extraction of copper(II) at a low
      amyloid/ligand ratio is essential for the re-introduction of copper in regular
      metal circulation in the brain. As, upon reduction, the Cu(+) is easily released
      from the bis(8-aminoquinoline) ligand unable to accommodate Cu(I), it should be
      taken by proteins with an affinity for copper. So, the tetradentate bis(8
      aminoquinoline) described here might act as a regulator of copper homeostasis. 

PMID- 25861568
TI  - Mesoporous ZnS-NiS Nanocomposites for Nonenzymatic Electrochemical Glucose
      Sensors.
AB  - Mesoporous ZnS-NiS composites are prepared via ion- exchange reactions using ZnS
      as the precursor. The prepared mesoporous ZnS-NiS composite materials have large
      surface areas (137.9 m(2) g(-1)) compared with the ZnS precursor. More
      importantly, the application of these mesoporous ZnS-NiS composites as
      nonenzymatic glucose sensors was successfully explored. Electrochemical sensors
      based on mesoporous ZnS-NiS composites exhibit a high selectivity and a low
      detection limit (0.125 MUm) toward the oxidation of glucose, which can mainly be
      attributed to the morphological characteristics of the mesoporous structure with
      high specific surface area and a rational composition of the two constituents. In
      addition, the mesoporous ZnS-NiS composites coated on the surface of electrodes
      can be used to modify the mass transport regime, and this alteration can, in
      favorable circumstances, facilitate the amperometric discrimination between
      species. These results suggest that such mesoporous ZnS-NiS composites are
      promising materials for nonenzymatic glucose sensors. 

PMID- 25861569
TI  - Glycerol as an efficient medium for the petasis borono-mannich reaction.
AB  - The multicomponent Petasis borono-Mannich (PBM) reaction is a useful tool for the
      preparation of complex molecules in a single step from boronic acids,
      aldehydes/ketones, and amines. Here, we describe the use of glycerol in the PBM
      reaction of salicylaldehydes or 2-pyridinecarbaldehyde with several boronic acids
      and secondary amines. From these readily available starting materials,
      alkylaminophenols, 2-substituted pyridines, and 2H-chromenes were prepared in
      reasonable to good yields. Glycerol was compared with other solvents, and in some
      cases, it provided the reaction product in higher yield. Crude glycerol, as
      generated by the biodiesel industry, was evaluated and found to be a suitable
      solvent for the PBM reaction, successfully expanding the potential use of this
      industry by-product. Based on density functional theory (DFT) calculations and
      the obtained experimental results, the involvement of glycerol-derived boronic
      esters in the reaction mechanism is suggested to be competitive with the free
      boronic acid pathway. Similar Gibbs free energies for the aryl migration from the
      boronate species to the iminium were determined for both mechanisms. 

PMID- 25861570
TI  - Structural Elucidation of the O-Antigen Polysaccharide from Escherichia coli
      O181.
AB  - Shiga-toxin-producing Escherichia coli (STEC) is an important pathogen associated
      to food-borne infection in humans; strains of E. coli O181, isolated from human
      cases of diarrhea, have been classified as belonging to this pathotype. Herein,
      the structure of the O-antigen polysaccharide (PS) from E. coli O181 has been
      investigated. The sugar analysis showed quinovosamine (QuiN), glucosamine (GlcN),
      galactosamine (GalN), and glucose (Glc) as major components. Analysis of the high
      resolution mass spectrum of the oligosaccharide (OS), obtained by
      dephosphorylation of the O-deacetylated PS with aqueous 48 % hydrofluoric acid,
      revealed a pentasaccharide composed of two QuiNAc, one GlcNAc, one GalNAc, and
      one Glc residue. The (1)H and (13)C NMR chemical shift assignments of the OS were
      carried out using 1 D and 2 D NMR experiments, and the OS was sequenced using a
      combination of tandem mass spectrometry (MS/MS) data and NMR (13)C NMR
      glycosylation shifts. The structure of the native PS was determined using NMR
      spectroscopy, and it consists of branched pentasaccharide repeating units joined
      by phosphodiester linkages: ->4)[alpha-l-QuipNAc-(1->3)]-alpha-d-GalpNAc6Ac-(1
      >6)-alpha-d-Glcp-(1->P-4)-alpha-l-QuipNAc-(1->3)-beta-d-GlcpNAc-(1->; the O
      acetyl groups represent 0.4 equivalents per repeating unit. Both the OS and PSs
      exhibit rare conformational behavior since two of the five anomeric proton
      resonances could only be observed at an elevated temperature. 

PMID- 25861571
TI  - Design, Synthesis, and Biological Evaluation of Tetra-Substituted Thiophenes as
      Inhibitors of p38alpha MAPK.
AB  - p38alpha mitogen-activated protein kinase (MAPK) plays a role in several cellular
      processes and consequently has been a therapeutic target in inflammatory
      diseases, cancer, and cardiovascular disease. A number of known p38alpha MAPK
      inhibitors contain vicinal 4-fluorophenyl/4-pyridyl rings connected to either a 5
      or 6-membered heterocycle. In this study, a small library of substituted
      thiophene-based compounds bearing the vicinal 4-fluorophenyl/4-pyridyl rings was
      designed using computational docking as a visualisation tool. Compounds were
      synthesised and evaluated in a fluorescence polarisation binding assay. The
      synthesised analogues had a higher binding affinity to the active phosphorylated
      form of p38alpha MAPK than the inactive nonphosphorylated form of the protein. 4
      (2-(4-fluorophenyl)thiophen-3-yl)pyridine had a K i value of 0.6 MUm to active
      p38alpha MAPK highlighting that substitution of the core ring to a thiophene
      retains affinity to the enzyme and can be utilised in p38alpha MAPK inhibitors.
      This compound was further elaborated using a substituted phenyl ring in order to
      probe the second hydrophobic pocket. Many of these analogues exhibited low
      micromolar affinity to active p38alpha MAPK. The suppression of neonatal rat
      fibroblast collagen synthesis was also observed suggesting that further
      development of these compounds may lead to potential therapeutics having
      cardioprotective properties. 

PMID- 25861572
TI  - Efficient regioselective ring opening of activated aziridine-2-carboxylates with
      [(18)f]fluoride.
AB  - Aziridines can undergo a range of ring-opening reactions with nucleophiles. The
      regio- and stereochemistry of the products depend on the substituents on the
      aziridine. Aziridine ring-opening reactions have rarely been used in
      radiosynthesis. Herein we report the ring opening of activated aziridine-2
      carboxylates with [(18)F]fluoride. The aziridine was activated for nucleophilic
      attack by substitution of various groups on the aziridine nitrogen atom. Fluorine
      18 radiolabelling was followed by ester hydrolysis and removal of the activation
      group. Totally regioselective ring opening and subsequent deprotection was
      achieved with tert-butyloxycarbonyl- and carboxybenzyl-activated aziridines to
      give alpha-[(18)F]fluoro-beta-alanine in good radiochemical yield. 

PMID- 25861573
TI  - Facile Hydrothermal Fabrication of Nano-Oxide Hollow Spheres using
      Monosaccharides as Sacrificial Templates.

PMID- 25861574
TI  - Is tuberculosis still the number one infectious disease in Korea?

PMID- 25861575
TI  - The Usefulness of the Tuberculosis Skin Test and the Interferon-gamma Release
      Assay in the Diagnosis of Latent Tuberculosis Infection in South Korea.
AB  - OBJECTIVES: South Koreans receive the bacillus Calmette-Guerin (BCG) vaccination,
      which influence the result of the tuberculin skin test (TST); however, only a few
      studies have described the usefulness of the TST and interferon-gamma release
      assay (IGRA) for diagnosing latent TB infection (LTBI). Therefore, our aim was to
      determine the usefulness of the TST and IGRA for diagnosing LTBI in a household
      contacts investigation. METHODS: We reviewed the 329 household contacts who
      visited Chung-Ang University Hospital (Seoul, Korea) from May 1, 2011 to February
      28, 2014. To evaluate the effectiveness of TST and IGRA for the diagnosis of
      LTBI, we examined the concordance rate between the two tests, based on age. We
      also evaluated the risk factors for LTBI. RESULTS: The concordance rate between
      the two tests in individuals 0-24 years, 25-54 years, and over 55 years were
      82.6% (kappa = 0.64, p < 0.01), 68.9% (kappa = 0.40, p < 0.01), and 68.4% (kappa
      = 0.35, p < 0.01), respectively. The ratio of positive TST to negative IGRA was
      higher in individuals 25-44 years old, whereas the ratio of negative TST to
      positive IGRA was higher in individuals older than 55 years old. Based on the
      TST, the risk factor for LTBI was a cavity (p < 0.01). When using IGRA, the risk
      factors were contact time (p = 0.04) and age over 55 years old (p = 0.02).
      CONCLUSION: The concordance rate between TST and IGRA was not good after the age
      of 25 years. The IGRA test reflects the known risk factors more exactly.

PMID- 25861576
TI  - Utilization of laboratory tests for tuberculosis and mycobacterial disease in
      Korea.
AB  - OBJECTIVES: In Korea, a large portion of tuberculosis (TB) patients are diagnosed
      and treated in private institutes. Laboratory tests are crucial for TB control.
      There are many possible problems using laboratory tests in the private sector. In
      this study, we aimed to investigate the characteristics and trends of utilizing
      laboratory tests for TB and mycobacterial diseases in the private sector by
      analyzing the National Health Insurance (NHI) database. METHODS: After selecting
      TB or other mycobacteria-related test items, we searched the number and cost of
      each item on the website of the Health Insurance Review and Assessment Service
      using the code of each test from 2007 to 2012. RESULTS: Our data revealed that
      the number and cost of tests drastically increased between 2007 and 2012. Culture
      and molecular tests primarily contributed to the tremendous increases. For each
      year, concentrated smearing and fluorochrome staining were more commonly used.
      The number of serologic tests for latent TB infection stagnated, despite the
      expansion of contact investigation. CONCLUSION: The NHI data could be
      considerably useful for understanding the utilization trends of laboratory tests
      for TB and mycobacterial diseases in Korea. Our data showed that TB laboratory
      systems have recently improved. In this study, many issues were noticed.
      Therefore, solutions to these issues are required and the continued monitoring of
      NHI data regarding laboratory diagnosis.

PMID- 25861577
TI  - Evaluation and comparison of molecular and conventional diagnostic tests for
      detecting tuberculosis in Korea, 2013.
AB  - OBJECTIVES: A fast and accurate diagnosis is necessary to control and eliminate
      tuberculosis (TB). In Korea, TB continues to be a serious public health problem.
      In this study, diagnostic tests on clinical samples from patients suspected to
      have TB were performed and the sensitivity and specificity of the various
      techniques were compared. The main objective of the study was to compare various
      diagnostic tests and evaluate their sensitivity and specificity for detecting
      tuberculosis. METHODS: From January 2013 to December 2013, 170,240 clinical
      samples from patients suspected to have TB were tested with smear microscopy,
      acid-fast bacilli culture, and real-time polymerase chain reaction (PCR). The
      test results were compared and data were analyzed. RESULTS: A total of 8216
      cultures tested positive for TB (positive detection rate, 4.8%). The
      contamination rate in the culture was 0.6% and the isolation rate of
      nontuberculous mycobacteria was 1.0%. The sensitivity and specificity of smear
      microscopy were 56.8% and 99.6%, respectively. The concordance rate between the
      solid and liquid cultures was 92.8%. Mycobacterium isolates were not detected in
      0.4% of the cases in the liquid culture, whereas no Mycobacterium isolates were
      detected in 6.8% of the cases in the solid culture. The sensitivity and
      specificity of real-time PCR for the solid culture were 97.2% and 72.4%,
      respectively, whereas the corresponding data for the liquid culture were 93.5%
      and 97.2%. CONCLUSION: The study results can be used to improve existing TB
      diagnosis procedure as well as for comparing the effectiveness of the assay tests
      used for detecting Mycobacterium tuberculosis isolates.

PMID- 25861579
TI  - Trends and Characteristics of HIV Infection among Suspected Tuberculosis Cases in
      Public Health Centers in Korea: 2001-2013.
AB  - OBJECTIVES: The Republic of Korea reports approximately 35,000 new tuberculosis
      (TB) patients each year, and the number of HIV-infected individuals is steadily
      increasing. Public health centers (PHCs) conduct TB diagnosis and treatment for
      risk groups in communities. This study aimed to identify possible trends and
      characteristics of HIV infection among suspected TB cases in PHCs. METHODS: Study
      subjects were suspected TB cases in PHCs who agreed to be tested for HIV from
      2001 to 2013. Trends in HIV seroprevalence were assessed through a series of
      annual cross-sectional analyses. We analyzed suspected TB cases, and HIV-infected
      individuals among suspected TB cases, by gender, age, nationality, and region.
      RESULTS: The number of suspected tuberculosis cases who took an HIV test in PHCs
      was approximately 6,000 each year from 2001 to 2013. Among the suspected TB cases
      who took an HIV test, the number of those aged 20-39 is gradually decreasing,
      while the number of those aged 50-69 is increasing. During this period, 32 HIV
      infected individuals were identified; the majority were men (94%), aged 30-49
      (68%), Korean (94%), and residents in a metropolitan area (53%). HIV
      seroprevalence decreased from 8.2 per 10,000 persons in 2001 to 1.9 per 10,000
      persons in 2013. CONCLUSION: This study has identified trends and characteristics
      of HIV infection among suspected tuberculosis cases in PHCs. This national data
      provides a basis for public health policy for HIV and tuberculosis infections.

PMID- 25861578
TI  - Results of tuberculosis contact investigation in congregate settings in Korea,
      2013.
AB  - OBJECTIVES: This study aimed to check the status of the contact investigation in
      congregate settings to eradicate tuberculosis (TB) in the Republic of Korea.
      METHODS: The "Integrated System for Disease and Public Health Management" is used
      for care and follow-up for patients and contacts of TB. We downloaded data for
      contact investigations conducted from January to December 2013. RESULTS: A total
      of 1,200 contact investigations in congregate settings were carried out by 25
      field investigators in 2013. We performed the status of contact investigation,
      TB, and LTBI rate by age, accept rate of LTBI treatment, and complete rate of
      LTBI treatment during 2013. A total of 1,547 index TB patients, 149,166 contacts,
      and 259 additional TB patients were found through the investigation.
      Kindergartens showed the highest LTBI rate, 19.8%, among educational facilities.
      The second highest was in elementary schools and the subtotal LTBI rate of
      educational facilities was 7.8%. Social welfare/correctional facilities and
      workplaces showed relatively high LTBI rates of 23.8% and 23.6%, respectively. By
      age, individuals >35 years showed the highest LTBI rate, followed by those aged 0
      4 years, 30-34 years, and 5-9 years, with rates of 18.1%, 16.4%, and 15.4%
      respectively. When comparing the tuberculin skin test (TST) positive conversion
      ratio by facility, middle school and high school were relatively high compared to
      the others. The accept rate of LTBI treatment in the workplace was lowest at 63%
      and the complete rate in elementary schools was lowest at 76.5%. CONCLUSION: TB
      contact investigation is considered as a meaningful strategy for preventing TB
      outbreaks in congregate settings and decreasing the prevalence of TB in young
      people. Results of this study could be used to establish the LTBI management
      policy.

PMID- 25861580
TI  - Activities of the korean institute of tuberculosis.
AB  - The Korean National Tuberculosis Association (KNTA) set up the Korean Institute
      of Tuberculosis (KIT) in 1970 to foster research and technical activities
      pertaining to tuberculosis (TB). The KNTA/KIT had successfully conducted a
      countrywide TB prevalence survey from 1965 to 1995 at 5-year intervals. The
      survey results (decline in TB rates) established Korea as a country that had
      successfully implemented national control programs for TB. The KIT developed the
      Korea Tuberculosis Surveillance System and the Laboratory Management Information
      System, both of which were transferred to the Korea Centers for Disease Control
      and Prevention after its establishment. The KIT functions as a central and
      supranational reference TB laboratory for microbiological and epidemiological
      research and provides training and education for health-care workers and medical
      practitioners. Recently, the KIT has expanded its activities to countries such as
      Ethiopia, Laos, and Timor-Leste to support TB control and prevention. The KIT
      will continue to support research activities and provide technical assistance in
      diagnosing the infection until it is completely eliminated in Korea. 

PMID- 25861581
TI  - A study on the relapse rate of tuberculosis and related factors in Korea using
      nationwide tuberculosis notification data.
AB  - OBJECTIVES: From the perspective of public health, tuberculosis (TB) remains an
      important issue that threatens health. Korea is an intermediate burden country
      with a TB incidence of 97/100,000 individuals. Among many TB control measures, a
      relapse rate of TB is one indicator that can be used to indirectly assess the
      level of TB control in countries and in communities. Relapse TB has an
      approximately 12% yearly incidence in Korea. This study aims to estimate the
      relapse rate of TB and to investigate the associated factors by using nationwide
      TB notification data in Korea. METHODS: The nationwide TB notification data in
      2005 was used with the exclusion criteria of duplicated reporting, foreign-born
      patients, outcome-died, and outcome-diagnosis changed. The data were double
      checked as to whether they were reported again during 2006-2010 and the estimated
      relapse rate of TB. Associated factors were analyzed by multivariate logistic
      regression with the variables of age, sex, registration type, results of sputum
      smear test, medication, and outcome of treatment. RESULTS: Among 45,434 TB
      patients in 2005, 4,371 patients were again reported as TB patients from 2006 to
      2010. Five hundred and sixty-four patients were reported more than twice and the
      cumulative number of relapses was 5,072 cases. The 5-year relapse rate was
      estimated as 9.62%. The relapse rate decreased yearly: 4.8% in 2006, 2.4% in
      2007, 1.6% in 2008, 1.4% in 2009, and 1.0% in 2010. Age, sex, registration type,
      tuberculosis type, and medication were independently associated with a relapse of
      TB. In the multivariate logistic regression analysis, the following factors were
      related: male sex, 40-49 years old; registration type, relapse, treatment after
      failure, treatment after default, transfer in, and other, the sputum smear
      positive pulmonary TB, and medications (including individuals taking 2-5 drugs).
      CONCLUSION: This study has estimated a 5-year relapse rate of TB in Korea that is
      slightly lower than the rate of relapse TB in the annual reports. This study
      could be conducted and cross-checked with data from the National Health Insurance
      in the future.

PMID- 25861582
TI  - High-risk behaviors related to intentional and unintentional harm in adolescents
      of zahedan, iran.
AB  - BACKGROUND: Adolescence and youth are life-threatening stages of development when
      a range of unsafe behaviors can harmfully affect a person's health and their
      social and educational performance. OBJECTIVES: The present study aimed to
      determine the incidence and prevalence of high-risk behaviors related to
      intentional and unintentional harm in adolescents of Zahedan (Iran). PATIENTS AND
      METHODS: This cross-sectional study included 1000 randomly selected male and
      female high school students of Zahedan, Iran. The Persian version of High Risk
      Behavior Questionnaire and Goldberg's 28-item General Health Questionnaire were
      used to collect data. Descriptive statistics (frequency and percentage) was used
      to analyze data. RESULTS: The most prevalent behaviors were not wearing seat belt
      (48%), riding a motorcycle without a helmet (42.3%) and involvement in physical
      conflicts (38.7%). Both the incidence and prevalence of the studied behaviors
      were higher in boys than girls. Moreover, greater prevalence of behaviors related
      to intentional and unintentional harm was observed in subjects with a drug
      abusing friend or family member. CONCLUSIONS: The incidence and prevalence of
      high-risk behaviors in the studied population were slightly lower compared to
      several other parts of the country and some other countries. Nevertheless, since
      the rates and trend are alarming, sectoral and intersectoral cooperation is
      indispensable to the implementation of preventive interventions at different
      levels of society. Such efforts would obviously require the help of experts in
      various fields and necessitate the assessment of sociocultural features of the
      population.

PMID- 25861583
TI  - Evaluation of anxiety and depression among female spouses of Iranian male drug
      dependents.
AB  - BACKGROUND: Existing evidences suggest the more vulnerability of spouses of drug
      dependents, in exposure to mental disorders. OBJECTIVES: This study aimed to
      evaluate the associated parameters of anxiety and depression among female spouses
      of male drug dependents. PATIENTS AND METHODS: With a cross-sectional design in
      2010, a total of 237 Iranian women were selected and divided into three groups:
      1. non-drug-dependent wives who had non-drug-dependent husbands (Group I), 2. non
      drug-dependent wives who had drug-dependent husbands (Group II), and 3. drug
      dependent wives who had drug-dependent husbands (Group III). Socio-demographic
      characteristics were collected by a checklist, and the levels of anxiety and
      depression were measured through the Hospital Anxiety and Depression Scale
      (HADS). Linear regression was applied for determination of anxiety and depression
      predictors. RESULTS: Mean age of the participants was about 35 years, and mean
      duration of marriage was 14 years. Drug dependence of the husband (P = 0.010) and
      lower monthly income of the family (P = 0.007) predicted the higher level of
      anxiety among the participants, while older age (P = 0.031), shorter marital
      duration (P = 0.016), and lower educational level (P = 0.045) in addition to
      spousal drug dependence (P = 0.023), and lower family income (P = 0.014) were
      significantly associated with higher levels of depression. CONCLUSIONS: Findings
      of the present study demonstrate that spousal drug dependence and lower monthly
      income were common predictors of anxiety and depression among spouses of drug
      dependents in Iran, while older age, shorter marital duration and lower
      educational level were predictors of depression. However, more research is needed
      to find casual relationships between spousal drug dependence and mental health in
      Iran.

PMID- 25861584
TI  - Prenatal and cardiovascular outcome in pregnant patients with dyspnea.
AB  - BACKGROUND: Pregnancy is a physiologic phenomenon in women, which leads to
      significant hemodynamic changes in cardiovascular system. Many patients reach
      reproductive age due to improvements in diagnosis and treatment of cardiac
      diseases. Dyspnea is a common complaint in pregnant women and can be a sign to
      refer patients for an easy and feasible workup such as echocardiography.
      OBJECTIVES: We aimed to evaluate dyspnea as a common complaint in pregnant women
      and its prenatal outcome. PATIENTS AND METHODS: Pregnant patients with dyspnea
      NYHA class > II were included. A thorough physical examination and routine lab
      tests were performed. Echocardiography was performed to rule out previous cardiac
      and lung diseases, anemia and thyroid disorders. It was repeated monthly till one
      month after delivery. Collected data was analyzed after one year. RESULTS: Fifty
      patients were enrolled with a mean age of 30.49 +/- 6.34 years. 58% of them, had
      NYHA class II, 40% III and 2% IV. Pulmonary rales were diagnosed in 8% and
      palpitation in 80%, while all had normal lab tests. Mean EF value was 52.26 +/-
      6.80; 54% had valvular diseases and 12% had pulmonary hypertension. Cesarean
      section was performed in 26, preeclampsia occurred in 7 and 21 had preterm labor.
      Three neonates had anomalies and six had an Apgar score below six. Mean birth
      weight was 2897 +/- 540.00 grams. A significant association was found between
      NYHA Class with valvular disease (P = 0.007) and sys PAP (P = 0.036); however, it
      had an inverse correlation with LV EF (P = 0.06). CONCLUSIONS: Dyspnea may
      coincide with cardiac dysfunction and poor prenatal outcome in pregnant patients.
      In such cases echocardiography is a feasible screening tool.

PMID- 25861585
TI  - Lung protective ventilation in Cardiac Surgery.

PMID- 25861586
TI  - Pulmonary capillary wedge pressure and natriuretic peptide levels in patients
      with sinus rhythm and severe left atrial enlargement following mitral valve
      surgery: early and late changes.
AB  - INTRODUCTION: Chronic mitral regurgitation is often accompanied by left atrial
      and ventricular remodeling and elevated natriuretic peptide levels. Our aim was
      to examine the relation between severe preoperative left atrial enlargement and
      changes in hemodynamics and natriuretic peptide levels after mitral valve
      surgery. METHODS: A prospective study was conducted including 40 consecutive
      patients in sinus rhythm, with severe degenerative mitral regurgitation. N
      terminal protype-B natriuretic peptide levels and hemodynamics were measured at
      predefined time points. An echocardiographic evaluation was performed the day
      before valve surgery and six months postoperatively. RESULTS: Patients with left
      atrial volume index >=60 mL/m(2), n=26, had higher baseline mean pulmonary
      capillary wedge pressure (17+/-9 mmHg vs 9+/-4 mmHg, p=0.010) and N-terminal
      protype-B natriuretic peptide (1326+/-2573 ng/L vs 233+/-221 ng/L, p=0.002) than
      patients with left atrial volume index <60 mL/m(2). The mean pulmonary capillary
      wedge pressure decreased to normal in patients with severe left atrial
      enlargement early after surgery, while it remained normal in patients without
      severe left atrial enlargement. The natriuretic peptide levels increased during
      the early postoperative period and decreased in both groups at 6-month follow-up.
      CONCLUSIONS: A severe left atrial enlargement in patients with chronic
      degenerative mitral regurgitation and sinus rhythm indicates higher pulmonary
      capillary wedge pressure and natriuretic peptide levels than in those without.
      These findings may support early referral to surgery and may facilitate
      perioperative management. The potential reversibility of left atrial enlargement
      after surgery may be associated with postoperative reductions in pulmonary
      capillary wedge pressure and natriuretic peptide levels.

PMID- 25861587
TI  - Peripheral diagnostic and interventional procedures using an automated injection
      system for carbon dioxide (CO2): case series and learning curve.
AB  - INTRODUCTION: The administration of iodinated contrast media in doses sufficient
      for diagnosis and procedural guidance, when coincident with renal insufficiency,
      presents a considerable risk of exacerbating and hastening renal failure. Carbon
      dioxide has been proposed in the past as an alternative, but only recently
      dedicated injection systems have become available. We aimed to review our ongoing
      experience with an automated carbon dioxide injector for peripheral diagnostic
      and interventional procedures. METHODS: Details on 21 patients undergoing
      peripheral procedures with carbon dioxide angiography were systematically
      collected. An automated injector enabling customized and repeated carbon dioxide
      injections was used in all cases, with iodinated contrast media used only as
      bailout. RESULTS: No major or minor complications occurred in these patients,
      either during the procedure or up to discharge. Comparison according to phase of
      the learning curve showed that with accruing experience operators relied
      progressively more on carbon dioxide only, as there was a significantly reduced
      need for additional iodinated contrast media injections per procedure (from 2.5+/
      2.1 to 0.6+/-2.1 injections per patient, p=0.005). Accordingly, in the second
      phase of our learning curve, iodinated contrast media were avoided in 91% of
      cases in comparison to 20% of procedures performed in the beginning of our
      experience (p=0.002). Concomitantly, no significant change in the duration of the
      procedure occurred. CONCLUSIONS: Carbon dioxide-based angiography using an
      automated injection system is feasible and safe in patients undergoing diagnostic
      or interventional procedures for infra-diaphragmatic conditions, especially for
      transcatheter renal sympathetic denervation.

PMID- 25861588
TI  - Microvolt T-wave alternans in patients undergoing elective coronary artery bypass
      grafting: a pilot study.
AB  - INTRODUCTION: We designed a prospective observational study targeting a selective
      population of patients undergoing elective coronary artery bypass grafting with
      normal systolic function. In this study we looked at the prevalence of pre
      operative microvolt T-wave alternans and if it predicts atrial fibrillation after
      surgery. METHODS: The inclusion criteria included all patients referred to the
      cardiothoracic outpatient clinic for elective bypass, who can perform aerobic
      exercise, with a recent exercise stress test exercising at least to 85% of the
      maximal predicted heart rate (220 - age) and with non-limiting chest pain at
      maximal exercise. Twenty patients met the inclusion/exclusion criteria between
      May 2008 and February 2010. The hospital course of those patients was followed,
      and in-hospital events were recorded. RESULTS: Nine out twenty (45%) of patients
      had a non-negative microvolt T-wave alternans tracing. Six patients (30%)
      developed new onset atrial fibrillation post surgery. Patients with non-negative
      microvolt level T-wave alternans are more likely to develop atrial fibrillation
      post coronary artery bypass grafting then patients with negative microvolt level
      T-wave alternans (p=0.05). CONCLUSIONS: This pilot study provides the first
      clinical evidence that patients with ischemic heart disease and normal systolic
      function have a high prevalence of abnormal microvolt T-wave alternans and might
      be at higher risk of sudden cardiac death. In addition our results show that
      microvolt level T-wave alternans predicts post coronary artery bypass grafting
      new onset atrial fibrillation.

PMID- 25861590
TI  - Use of lyophilized fibrinogen concentrate in cardiac surgery: a systematic
      review.
AB  - INTRODUCTION: Use of fibrinogen concentrate among cardiac anesthetists is growing
      especially for the benefits related to the reduction in the administration of
      bleeding and allogeneic blood components, which are exacerbated by
      cardiopulmonary bypass. Moreover, these products underwent complete viral
      inactivation, reducing the risks of contamination associated with transfusion.
      The purpose of this research was to review the literature looking for randomized
      controlled trials regarding fibrinogen concentrate and its benefits in cardiac
      surgery. METHOD: The papers used in this review were searched in BioMed Central,
      PubMed, Embase, and the Cochrane Central Register of Clinical Trial by two
      investigators. The full search strategy was performed to identify all randomized
      controlled trials in the last 10 years, comparing the use of fibrinogen in the
      adult treatment of perioperative bleeding to standard treatment or placebo.
      RESULTS: Only four articles matching the selection criteria for final analysis
      were identified and only 79 patients received therapy with fibrinogen concentrate
      in randomized trials performed in cardiac surgery. CONCLUSIONS: During the last
      10 years, few randomized controlled trials were performed to confirm the real
      benefit of using lyophilized fibrinogen to reduce bleeding in cardiac surgery.
      However, when indicated, it may be a good option in order to reduce the
      consumption of blood products in the treatment of perioperative bleeding,
      following an algorithm based on point-of-care testing.

PMID- 25861589
TI  - Beneficial impact of levosimendan in critically ill patients with or at risk for
      acute renal failure: a meta-analysis of randomized clinical trials.
AB  - INTRODUCTION: The incidence of Acute Kidney Injury is nowadays high in critically
      ill patients. Its etiology is multifactorial and a primary role is played by low
      cardiac output syndrome. Everything targeted to normalize cardiac output should
      increase the renal perfusion and abolish the secondary vasoconstriction.
      Levosimendan is a calcium sensitizer drug with inotropic properties that improves
      cardiac output and seems to increase renal blood flow. The aim of this meta
      analysis was to evaluate the role of levosimendan in critically ill patients with
      or at risk of Acute Kidney Injury. METHODS: We performed a meta-analysis of 
      randomized controlled trials searching for trials that compared levosimendan with
      any comparator. The endpoints were the number of patients receiving Renal
      Replacement Therapy after randomization and the number of patients developing
      Acute Kidney Injury. RESULTS: Final analysis included 33 trials and 3,879
      patients (2,024 levosimendan and 1,855 control). The overall analysis showed that
      the use of levosimendan was associated with a significant reduction in the risk
      of Renal Replacement Therapy (17 of 492 [3.5%] in the levosimendan group versus
      37 of 427 [8.7%] in the control group, relative risk =0.52 [0.32 to 0.86], p for
      effect =0.01) and of Acute Kidney Injury (114 of 1,598 [7.1%] in the levosimendan
      group versus 143 of 1,529 [9.4%] in the control arm, relative risk =0.79 [0.63 to
      0.99], p for effect =0.048). CONCLUSIONS: This meta-analysis suggests that the
      use of levosimendan is associated with a significant reduction of Renal
      Replacement Therapy in critically ill patients.

PMID- 25861591
TI  - Haemodynamic response at double lumen bronchial tube placement - Airtraq vs.
      MacIntosh laryngoscope, a randomised controlled trial.
AB  - INTRODUCTION: Tracheal intubation causes a haemodynamic response that might be
      harmful for patients. The Airtraq(r) laryngoscope has been shown to decrease the
      haemodynamic response to single-lumen tube intubation. We hypothesised that
      double-lumen bronchial tube placement with the Double-lumen Airtraq(r)
      laryngoscope would cause a reduced haemodynamic response and decreased
      catecholamine release compared with the MacIntosh laryngoscope. METHODS: Forty
      adult patients were randomly assigned to the Airtraq(r) group or to the MacIntosh
      group. Intubation with either the Airtraq(r) or the MacIntosh laryngoscope was
      performed two minutes after standardised induction of anaesthesia. Arterial blood
      pressure, heart rate, catecholamine levels, bispectral index and duration of the
      intubation procedure were measured. RESULTS: Mean (standard deviation [95%
      confidence interval]) systolic arterial blood pressure at laryngoscopy with the
      Airtraq(r) laryngoscope was 124 (34 [106 to 141]) mmHg and, with the MacIntosh
      laryngoscope, it was 110 (25 [99 to 122]) mmHg (p=1.0). Heart rate at
      laryngoscopy with the Airtraq(r) laryngoscope was 75 beats.min-1 (16 [67 to 83])
      and, with the MacIntosh laryngoscope, it was 64 beats.min-1 (14 [58 to 71])
      (p=0.71). Adrenaline levels post-intubation were 54.3 ng.l-1 (41.5) [29.3 to
      79.4] in the Airtraq(r) group and 30.5 ng.l-1 (25.6) [15.1 to 46.0] in the
      MacIntosh group (p=0.016). The duration of intubation with the Airtraq(r)
      laryngoscope was 88 s (31 [72-104]) while, with the MacIntosh laryngoscope, the
      duration was 75 s (35 [59-92]) (p=0.26). CONCLUSIONS: The use of the Double-lumen
      Airtraq(r) laryngoscope provides no benefit regarding stress response compared to
      the MacIntosh laryngoscope.

PMID- 25861592
TI  - Biomarkers, diagnosis and management of sepsis-induced acute kidney injury: a
      narrative review.
AB  - Sepsis is a leading cause of acute kidney injury in clinical practice. The
      diagnosis of sepsis-induced acute kidney injury requires the diagnosis of sepsis
      and subsequent occurrence of acute kidney injury. The current definition for
      acute kidney injury is based on Scr and urine output, which is limited by the
      delayed identification of such patients. Numerous novel biomarkers have been
      found to be up-regulated in kidney injury, among which cystatin C and neutrophil
      gelatinase-associated lipocalin are the most studied. In the management of sepsis
      induced acute kidney injury, early goal directed therapy may be potentially
      useful, but requires further validation in large clinical trials. It is well
      known that fluid overload is harmful in septic patients with established acute
      kidney injury and should be avoided. Renal replacement therapy is the mainstay
      treatment for the severe form of sepsis-induced acute kidney injury. However,
      there is still no consensus on the definition of timing and dosing in clinical
      practice, and the optimal timing and dosing are still unknown. 

PMID- 25861593
TI  - Ventilator strategies for VV ECMO management with concomitant tracheal injury and
      H1N1 influenza.
AB  - Tracheal injury is a rare but highly morbid complication of endotracheal
      intubation. Recent reviews have advocated conservative management of these
      injuries without operative intervention. Extracorporeal membrane oxygenation may
      be a useful tool in non-operative management of tracheal injury in the setting of
      severe respiratory failure and need for prolonged intubation. We present a
      morbidly obese 33 year-old-female with H1N1 influenza pneumonia complicated by
      acute respiratory distress syndrome and bacterial super-infection who sustained a
      post-intubation tracheal injury. Concomitant tracheal injury and acute lung
      injury pose a difficult ventilation dilemma. This patient was successfully
      managed by venovenous extracorporeal membrane oxygenation, high frequency
      oscillator ventilation, proning position and tube thoracostomy. The venovenous
      extracorporeal membrane oxygenation and ventilator management were essential for
      this patient's recovery. 

PMID- 25861594
TI  - Idiopathic ascending aortitis as a rare cause of supravalvular aortic stenosis.

PMID- 25861595
TI  - Hybrid endovascular repair of Kommerell diverticulum and aberrant right
      subclavian artery in a patient with repaired coarctation of the aorta.

PMID- 25861596
TI  - McConnell's echocardiographic sign in acute pulmonary embolism: still a useful
      pearl.

PMID- 25861597
TI  - Isoproterenol infusion in septic shock.

PMID- 25861598
TI  - No coronary artery occlusion in septic shock: Isoproterenol infusion should not
      be discouraged.

PMID- 25861599
TI  - Paravertebral analgesia in transapical transcatheter aortic valve replacement.

PMID- 25861600
TI  - Plasmodium falciparum gametocytes: playing hide and seek.

PMID- 25861601
TI  - Translating basic science discoveries to clinical practice-Let us not repeat the
      naivete of the pre-omics era.

PMID- 25861603
TI  - What is the best way to determine the cause of adolescent idiopathic scoliosis?

PMID- 25861602
TI  - Circulating donor-derived cell-free DNA: a true biomarker for cardiac allograft
      rejection?

PMID- 25861604
TI  - The importance of intake: a gut feeling.
AB  - Limiting enteric sodium absorption is an attractive option when renal sodium
      excretion is disturbed. An effective approach in the gut appears to be inhibition
      of the electroneutral Na(+)/H(+) exchangers (NHE), in particular NHE3. Recently,
      fluid retention, blood pressure and target organ injury were limited in rats with
      cardiorenal syndrome when treated with the NHE3 inhibitor tenapanor. The downside
      was that the osmotic fecal load leads to watery feces. Tenapanor also induced
      marked reductions in enteric phosphorus absorption in rats with cardiorenal
      syndrome on a high phosphorus intake and resulted in marked reductions in renal
      injury and practically prevented vascular calcification. We have yet to discover
      the clinical relevance in volume terms and vascular calcifications in patients in
      relation to the tolerated dose. However, even if the tenapanor-induced reduction
      in sodium adsorption is limited in humins, combination of tenapanor therapy with
      diuretics may be an interesting option in selected patients. 

PMID- 25861605
TI  - Prognostic value of neutrophil to lymphocyte ratio for gastric cancer.
AB  - BACKGROUND: Although the prognostic value of the neutrophil to lymphocyte ratio
      (NLR) in gastric cancer (GC) patients has been investigated by many studies, the
      results are heterogeneous. The objective of this systematic review is to
      ascertain the prognostic value of NLR in GC patients. METHODS: PubMed and Embase
      were retrieved to identify potential studies published before 8 June, 2014.
      Newcastle-Ottawa Scale (NOS) for cohort study was used to assess the quality of
      all eligible studies. RESULTS: Of the 20 studies included in this systematic
      review, 17 studies investigated the effect of NLR on overall survival (OS), 11
      studies reported that NLR negatively affected OS in their multivariante analysis,
      and 16 studies reported that NLR negatively affected OS in univariate analysis.
      Three studies investigated the effect of NLR on progression-free survival (PFS),
      reporting that increased NLR was associated with worse PFS. Four studies
      investigated the effect of NLR on disease-free survival (DFS), two of which
      reported that increased NLR was associated with worse DFS. Two studies
      investigated the effect of NLR on disease special survival (DSS), but neither
      observed any significant association between NLR and DSS. The major design
      deficiencies of the studies available were retrospective data collection,
      inadequacy of follow-up cohorts, and unavailability of the method used for
      outcome assessment. CONCLUSIONS: Based on the above findings, we conclude that
      NLR may be a useful prognostic index (PI) for GC. In addition, future studies
      with prospective design, long-term follow-up and fully adjusted confounding
      factors are needed to rigorously assess the prognostic value of NLR for GC.

PMID- 25861606
TI  - Risk of coronary artery disease in patients with ankylosing spondylitis: a
      systematic review and meta-analysis.
AB  - OBJECTIVE: To investigate the association between coronary artery disease (CAD)
      and ankylosing spondylitis (AS). METHODS: We conducted a systematic review and
      meta-analysis of observational studies that reported relative risks, hazard
      ratios, standardized prevalence ratio or standardized incidence ratios with 95%
      confidence comparing CAD risk in patients with AS versus non-AS controls. Pooled
      risk ratios and 95% confidence intervals (CIs) were calculated using a random
      effect, generic inverse variance of DerSimonian and Laird. RESULTS: Out of 229
      potentially relevant articles, ten studies (five retrospective cohort studies and
      five cross-sectional studies) were identified and included in our data analysis.
      The overall pooled risk ratio of CAD in patients with AS was 1.41 (95% CI: 1.29
      1.54). The pooled risk ratios for cross-sectional and cohort studies were 2.08
      (95% CI: 1.28-3.40) and 1.36 (95% CI: 1.31-1.41), respectively. The statistical
      heterogeneity of this meta-analysis was moderate with an I(2) of 56%.
      CONCLUSIONS: Our study demonstrated a statistically significant increased CAD
      risk among patients with AS with 41% excess risk.

PMID- 25861607
TI  - beta-glucan affects mucosal immunity in children with chronic respiratory
      problems under physical stress: clinical trials.
AB  - BACKGROUND: The role of beta-glucan in children with respiratory problems is
      getting more and more attention. In this report we focused on the effects of 30
      days oral supplementation with beta-glucan on physical activity and immune status
      of children with respiratory problems. METHODS: We measured the level of sIgA,
      eNO and physical activity [using a 6-minute walking test (6MWT)] in 77 children
      and evaluated the effect of 100 mg/day oral dose. RESULTS: We found a significant
      difference between males and females in physical endurance. In the glucan group,
      the positive effects of glucan were significant in both age groups. In the glucan
      group, we found significant decrease of eNO levels and stabilization of the sIgA
      levels. CONCLUSIONS: Short-term oral application of natural immunomodulator beta
      glucan stimulated physical endurance in children with respiratory problems and,
      via stabilization of the sIgA levels, helps their mucosal immunity.

PMID- 25861608
TI  - Pneumothorax: an up to date "introduction".
AB  - The pneumothorax is an abnormal collection of air or gas in the pleural space
      that separates the lung from the chest wall. Like pleural effusion where a large
      abnormal concentration of fluid (>100 mL) is liquid buildup in that space,
      pneumothorax may interfere with normal breathing. A medical term that it is used
      is the collapsed lung, although that term may also refer to atelectasis. There
      are two major types of pneumothorax; there is one that occurs without an apparent
      cause and in the absence of significant lung disease, while the so called;
      "secondary" pneumothorax occurs in the presence of existing lung pathology. In a
      minority of cases, the amount of air in the chest increases markedly when a one
      way valve is formed by an area of damaged tissue, leading to a third type of
      pneumothorax, called "tensioned". 

PMID- 25861609
TI  - Heimlich valve and pneumothorax.
AB  - The Heimlich valve is a small one-way valve used for chest drainage that empties
      into a flexible collection device and prevents return of gases or fluids into the
      pleural space. The Heimlich valve is less than 13 cm (5 inches) long and
      facilitates patient ambulation. Currently there are several systems in the
      market. It can be used in many patients instead of a traditional water seal
      drainage system. The Heimlich chest drainage valve was developed so that the
      process of draining the pleural cavity could be accomplished in a safe,
      relatively simple, and efficient manner. This valve system has replaced the
      cumbersome underwater drainage bottle system. Moreover; the Heimlich valve system
      connects to chest tubing and allows fluid and air to pass in one direction only.
      This system functions in any position, and it does not ever need to be clamped, a
      regulated suction can be attached to it if necessary. The valve drains into a
      plastic bag that can be held at any level, allowing the patient undergoing chest
      drainage to be ambulatory simply by carrying the bag. In the current mini review
      we will present the Heimlich valve system and method of insertion. 

PMID- 25861612
TI  - Robotic thoracic surgery of the anterior superior mediastinal bronchogenic cyst.

PMID- 25861610
TI  - Minimally invasive procedures.
AB  - Minimally invasive procedures, which include laparoscopic surgery, use state-of
      the-art technology to reduce the damage to human tissue when performing surgery.
      Minimally invasive procedures require small "ports" from which the surgeon
      inserts thin tubes called trocars. Carbon dioxide gas may be used to inflate the
      area, creating a space between the internal organs and the skin. Then a miniature
      camera (usually a laparoscope or endoscope) is placed through one of the trocars
      so the surgical team can view the procedure as a magnified image on video
      monitors in the operating room. Specialized equipment is inserted through the
      trocars based on the type of surgery. There are some advanced minimally invasive
      surgical procedures that can be performed almost exclusively through a single
      point of entry-meaning only one small incision, like the "uniport" video-assisted
      thoracoscopic surgery (VATS). Not only do these procedures usually provide
      equivalent outcomes to traditional "open" surgery (which sometimes require a
      large incision), but minimally invasive procedures (using small incisions) may
      offer significant benefits as well: (I) faster recovery; (II) the patient remains
      for less days hospitalized; (III) less scarring and (IV) less pain. In our
      current mini review we will present the minimally invasive procedures for
      thoracic surgery. 

PMID- 25861611
TI  - Prophylactic antibiotic administration for post cardiothoracic surgery sternal
      wounds: a retrospective study.
AB  - BACKGROUND: Cardiothoracic surgery sternal infections are difficult to treat
      situations. Until now there are no clear guidelines which or if an antibiotic
      could be used as prophylactic treatment. PATIENTS AND METHODS: We collected
      retrospectively data from 535 patients from our hospital which underwent
      cardiothoracic surgery and recorded several biological parameters and technical
      aspects of the surgery. RESULTS: It was observed that patients to whom vancomycin
      was administered had less post surgery infection than those to whom begalin was
      administered. Male who were treated with vancomycin it was observed that they had
      1.67 chances to be treated properly than female. Patients which were hospitalized
      for more than 7 days before surgery had 62.6% higher chances for post surgery
      infection. CONCLUSIONS: It was observed that vancomycin can be used as a
      prophylactic treatment for cardiothoracic surgeries acting efficiently against
      sternal wounds.

PMID- 25861613
TI  - Professor Ali Zamir Khan: the robotic surgery experience.

PMID- 25861614
TI  - Our health, our care!

PMID- 25861615
TI  - Erratum: Impact of BRAF mutation status in the prognosis of cutaneous melanoma:
      an area of ongoing research: Erratum.
AB  - [This corrects the article on p. 24 in vol. 3, PMID: 25738144.]. 

PMID- 25861616
TI  - High-Throughput Sequencing Reveals Diverse Sets of Conserved, Nonconserved, and
      Species-Specific miRNAs in Jute.
AB  - MicroRNAs play a pivotal role in regulating a broad range of biological
      processes, acting by cleaving mRNAs or by translational repression. A group of
      plant microRNAs are evolutionarily conserved; however, others are expressed in a
      species-specific manner. Jute is an agroeconomically important fibre crop;
      nonetheless, no practical information is available for microRNAs in jute to date.
      In this study, Illumina sequencing revealed a total of 227 known microRNAs and 17
      potential novel microRNA candidates in jute, of which 164 belong to 23 conserved
      families and the remaining 63 belong to 58 nonconserved families. Among a total
      of 81 identified microRNA families, 116 potential target genes were predicted for
      39 families and 11 targets were predicted for 4 among the 17 identified novel
      microRNAs. For understanding better the functions of microRNAs, target genes were
      analyzed by Gene Ontology and their pathways illustrated by KEGG pathway
      analyses. The presence of microRNAs identified in jute was validated by stem-loop
      RT-PCR followed by end point PCR and qPCR for randomly selected 20 known and
      novel microRNAs. This study exhaustively identifies microRNAs and their target
      genes in jute which will ultimately pave the way for understanding their role in
      this crop and other crops. 

PMID- 25861617
TI  - DNA-Encoded Chromatin Structural Intron Boundary Signals Identify Conserved Genes
      with Common Function.
AB  - The regulation of metazoan gene expression occurs in part by pre-mRNA splicing
      into mature RNAs. Signals affecting the efficiency and specificity with which
      introns are removed have not been completely elucidated. Splicing likely occurs
      cotranscriptionally, with chromatin structure playing a key regulatory role. We
      calculated DNA encoded nucleosome occupancy likelihood (NOL) scores at the
      boundaries between introns and exons across five metazoan species. We found that
      (i) NOL scores reveal a sequence-based feature at the introns on both sides of
      the intron-exon boundary; (ii) this feature is not part of any recognizable
      consensus sequence; (iii) this feature is conserved throughout metazoa; (iv) this
      feature is enriched in genes sharing similar functions: ATPase activity, ATP
      binding, helicase activity, and motor activity; (v) genes with these functions
      exhibit different genomic characteristics; (vi) in vivo nucleosome positioning
      data confirm ontological enrichment at this feature; and (vii) genes with this
      feature exhibit unique dinucleotide distributions at the intron-exon boundary.
      The NOL scores point toward a physical property of DNA that may play a role in
      the mechanism of pre-mRNA splicing. These results provide a foundation for
      identification of a new set of regulatory DNA elements involved in splicing
      regulation. 

PMID- 25861618
TI  - Congenital heart defects are rarely caused by mutations in cardiac and smooth
      muscle actin genes.
AB  - BACKGROUND: Congenital heart defects (CHDs) often have genetic background due to
      missense mutations in cardiomyocyte-specific genes. For example, cardiac actin
      was shown to be involved in pathogenesis of cardiac septum defects and smooth
      muscle actin in pathogenesis of aortic aneurysm in combination with patent ductus
      arteriosus (PDA). In the present study, we further searched for mutations in
      human alpha-cardiac actin (ACTC1) and smooth muscle alpha-actin (ACTA2) genes as
      a possible cause of atrial septum defect type II (ASDII) and PDA. FINDINGS: Total
      genomic DNA was extracted from peripheral blood of 86 individuals with ASDs and
      100 individuals with PDA. Coding exons and flanking intron regions of ACTC1
      (NM_005159.4) and ACTA2 (NM_001613) were amplified by PCR with specific primers
      designed according to the corresponding gene reference sequences. PCR fragments
      were directly sequenced and analyzed. Sequence analysis of ACTC1 and ACTA2 did
      not identify any nucleotide changes that altered the coding sense of the genes.
      In ACTC1 gene, we were able to detect one previously described nucleotide
      polymorphism (rs2307493) resulting in a synonymous substitution. The frequency of
      this SNP was similar in the study and control group, thus excluding it from the
      possible disease-associated variants. CONCLUSIONS: Our results confirmed that the
      mutations in ACTC1 gene are rare (at least <1%) cause of ASDII. Mutations in
      ACTA2 gene were not detected in patients with PDA, thus being excluded from the
      list of frequent PDA-associated genetic defects.

PMID- 25861619
TI  - Primary care quality among different health care structures in Tibet, China.
AB  - OBJECTIVE: To compare the primary care quality among different health care
      structures in Tibet, China. METHODS: A self-administered questionnaire survey
      including Primary Care Assessment Tool-Tibetan version was used to obtain data
      from a total of 1386 patients aged over 18 years in the sampling sites in two
      prefectures in Tibet. Multivariate analysis was performed to assess the
      association between health care structures and primary care quality while
      controlling for sociodemographic and health care characteristics. RESULTS: The
      services provided by township health centers were more often used by a poor, less
      educated, and healthy population. Compared with prefecture (77.42) and county
      hospitals (82.01), township health centers achieved highest total score of
      primary care quality (86.64). Factors that were positively and significantly
      associated with higher total assessment scores included not receiving inpatient
      service in the past year, less frequent health care visits, good self-rated
      health status, lower education level, and marital status. CONCLUSIONS: This study
      showed that township health centers patients reported better primary care quality
      than patients visiting prefecture and county hospitals. Government health reforms
      should pay more attention to THC capacity building in Tibet, especially in the
      area of human resource development.

PMID- 25861620
TI  - Aging: mitigation and intervention strategies.

PMID- 25861621
TI  - Long-term clinical practice experience with cinacalcet for treatment of
      hypercalcemic hyperparathyroidism after kidney transplantation.
AB  - Within this prospective, open-label, self-controlled study, we evaluated the long
      term effects of the calcimimetic cinacalcet on calcium and phosphate homeostasis
      in 44 kidney transplant recipients (KTRs) with hypercalcemic hyperparathyroidism
      by comparing biochemical parameters of mineral metabolism between pre- and
      posttreatment periods. Results are described as mean differences (95% CIs)
      between pre- and posttreatment medians that summarize all repeated measurements
      of a parameter of interest between the date of initial hypercalcemia and
      cinacalcet initiation (median of 1.6 (IQR: 0.6-3.8) years) and up to four years
      after treatment start, respectively. Cinacalcet was initiated after 1.8 (0.8-4.7)
      years posttransplant and maintained for 6.2 (3.9-7.6) years. It significantly
      decreased total serum calcium (-0.30 (-0.34 to -0.26) mmol/L, P < 0.001) and
      parathyroid hormone levels (-79 (-103 to -55) pg/mL, P < 0.001). Serum levels of
      inorganic phosphate (Pi) and renal tubular reabsorption of phosphate to
      glomerular filtration rate (TmP/GFR) increased simultaneously (Pi: 0.19 (0.15
      0.23) mmol/L, P < 0.001, TmP/GFR: 0.20 (0.16-0.23) mmol/L, P < 0.001). In
      summary, cinacalcet effectively controlled hypercalcemic hyperparathyroidism in
      KTRs in the long-term and increased low Pi levels without causing
      hyperphosphatemia, pointing towards a novel indication for the use of cinacalcet
      in KTRs. 

PMID- 25861622
TI  - Plantar loading reflects ulceration risks of diabetic foot with toe deformation.
AB  - Diabetes has been one of the most common chronic diseases all over the world. The
      purpose of this study was to quantitatively assess the foot loading
      characteristics of diabetic patients with fifth-toe deformity through a
      comparative analysis with diabetic patients with healthy and normal feet. Six
      neuropathic diabetic female subjects with the fifth-toe deformation and six age
      matched neuropathic diabetic controls without any feet deformities participated
      in the walking test. Dynamic barefoot plantar pressure was measured with Novel
      EMED force plate. Peak pressure and pressure-time integral for all 7 foot regions
      (rearfoot, midfoot, lateral forefoot, central forefoot, medial forefoot, great
      toe, and other toes) were collected. Peak pressure was significantly higher in
      the patients with toe deformity in rearfoot, central forefoot, and great toe
      regions compared with the control group. Meanwhile, loading sustaining period
      extended longer in great toe region of deformed group than in that of the control
      group, and the center of pressure was nearly in the big toe region during toe
      offstage. Diabetic patients with fifth-toe deformity could have plantar contact
      area reduction in the other toes part and increased loading to the great toe
      part. The result showed that fifth-toe deformity was associated with potential
      ulceration risk especially in hallux region. 

PMID- 25861623
TI  - Autophagy and liver ischemia-reperfusion injury.
AB  - Liver ischemia-reperfusion (I-R) injury occurs during liver resection, liver
      transplantation, and hemorrhagic shock. The main mode of liver cell death after
      warm and/or cold liver I-R is necrosis, but other modes of cell death, as
      apoptosis and autophagy, are also involved. Autophagy is an intracellular self
      digesting pathway responsible for removal of long-lived proteins, damaged
      organelles, and malformed proteins during biosynthesis by lysosomes. Autophagy is
      found in normal and diseased liver. Although depending on the type of ischemia,
      warm and/or cold, the dynamic process of liver I-R results mainly in adenosine
      triphosphate depletion and in production of reactive oxygen species (ROS), leads
      to both, a local ischemic insult and an acute inflammatory-mediated reperfusion
      injury, and results finally in cell death. This process can induce liver
      dysfunction and can increase patient morbidity and mortality after liver surgery
      and hemorrhagic shock. Whether autophagy protects from or promotes liver injury
      following warm and/or cold I-R remains to be elucidated. The present review aims
      to summarize the current knowledge in liver I-R injury focusing on both the
      beneficial and the detrimental effects of liver autophagy following warm and/or
      cold liver I-R. 

PMID- 25861625
TI  - The high PMNs phagocytosis resistance of enterococcal isolates from RTx patients.
AB  - Infections caused by opportunistic pathogens such as enterococci remain difficult
      to manage, especially in immunocompromised patients. Because of infections'
      limited symptoms in such patients the additional problems are to find proper
      diagnostic criteria and the management of infection. Here we aimed to compare the
      resistance of commensal enterococcal strains and RTx patients' isolates, to PMNs
      phagocytosis. Thirty-six enterococcal urine and faecal isolates from RTx patients
      and 17 faecal isolates from healthy volunteers were cultured in planktonic and
      biofilm forms in 37 degrees C or 42 degrees C. Another tested variable was the
      addition of immunosuppressant to the culture media. Bacterial cells were stained
      with fluorescent reporter (CFDA, PI) and incubated with PMNs. Results of
      phagocytosis were estimated as a mean fluorescence intensity (MFI) of PMNs using
      flow cytometry. Commensal enterococci cultured in all abovementioned (37 degrees
      C and 42 degrees C/the addition of immunosuppressant) conditions were less
      resistant to phagocytosis compared to RTx isolates. Observed significant
      difference in phagocytosis resistance suggests that patients in immunosuppression
      are colonized with high risk strains which may lead to the development of
      infection. 

PMID- 25861624
TI  - Wharton's jelly derived mesenchymal stem cells: future of regenerative medicine?
      Recent findings and clinical significance.
AB  - Around 5 million annual births in EU and 131 million worldwide give a unique
      opportunity to collect lifesaving Wharton's jelly derived mesenchymal stem cells
      (WJ-MSC). Evidences that these cells possess therapeutic properties are
      constantly accumulating. Collection of WJ-MSC is done at the time of delivery and
      it is easy and devoid of side effects associated with collection of adult stem
      cells from bone marrow or adipose tissue. Likewise, their rate of proliferation,
      immune privileged status, lack of ethical concerns, nontumorigenic properties
      make them ideal for both autologous and allogeneic use in regenerative medicine
      applications. This review provides an outline of the recent findings related to
      WJ-MSC therapeutic effects and possible advantage they possess over MSC from
      other sources. Results of first clinical trials conducted to treat immune
      disorders are highlighted. 

PMID- 25861626
TI  - Preclinical evaluation of the immunomodulatory properties of cardiac adipose
      tissue progenitor cells using umbilical cord blood mesenchymal stem cells: a
      direct comparative study.
AB  - Cell-based strategies to regenerate injured myocardial tissue have emerged over
      the past decade, but the optimum cell type is still under scrutiny. In this
      context, human adult epicardial fat surrounding the heart has been characterized
      as a reservoir of mesenchymal-like progenitor cells (cardiac ATDPCs) with
      potential clinical benefits. However, additional data on the possibility that
      these cells could trigger a deleterious immune response following implantation
      are needed. Thus, in the presented study, we took advantage of the well
      established low immunogenicity of umbilical cord blood-derived mesenchymal stem
      cells (UCBMSCs) to comparatively assess the immunomodulatory properties of
      cardiac ATDPCs in an in vitro allostimulatory assay using allogeneic mature
      monocyte-derived dendritic cells (MDDCs). Similar to UCBMSCs, increasing amounts
      of seeded cardiac ATDPCs suppressed the alloproliferation of T cells in a dose
      dependent manner. Secretion of proinflammatory cytokines (IL6, TNFalpha, and
      IFNgamma) was also specifically modulated by the different numbers of cardiac
      ATDPCs cocultured. In summary, we show that cardiac ATDPCs abrogate T cell
      alloproliferation upon stimulation with allogeneic mature MDDCs, suggesting that
      they could further regulate a possible harmful immune response in vivo.
      Additionally, UCBMSCs can be considered as valuable tools to preclinically
      predict the immunogenicity of prospective regenerative cells. 

PMID- 25861627
TI  - PTEN plays an important role in thrombin-mediated lung cancer cell functions.
AB  - Thrombin and its membrane receptor, protease-activated receptor 1 (PAR1), have
      been reported to promote the development of lung cancer in vitro and in vivo.
      However, the intracellular molecular mechanism or signaling pathway that mediates
      the cytological effects after the thrombin-receptor interaction is poorly
      understood. Our previous study observed that the expression of phosphatase and
      tensin homolog deleted on chromosome 10 (PTEN) was downregulated in thrombin
      stimulated lung cancer. In this study, the role of PTEN in thrombin-mediated cell
      function and the corresponding cell signaling pathway were studied in lung cancer
      cell Glc-82. The results indicated that thrombin downregulates the PTEN
      expression level and that PTEN plays an important role in thrombin-mediated Glc
      82 functions, including cell cycle progression, cell apoptosis, and cell
      migration. The PI3K/AKT signaling pathway and its related proteins, including p27
      and S phase kinase associated protein 2 (Skp2), are involved in the effects
      induced by PTEN downregulation. PAR1 plays a role in thrombin-mediated reduction
      of PTEN expression. This study suggested that the PTEN/PI3K/AKT signaling pathway
      plays an important role in thrombin/PAR1-mediated lung cancer cell growth and
      migration. 

PMID- 25861628
TI  - Intraoperative computed tomography versus Perdriolle and scoliometer evaluation
      of spine rotation in adolescent idiopathic scoliosis.
AB  - Numerous indirect methods for apical vertebral rotation (AVR) measurement have
      been reported and none of them seems to be as accurate as computed tomography
      evaluation. The aim of this study was to compare spinal rotation changes during
      innovative technique of intraoperative computed tomography (ICT) evaluation with
      indirect methods such as Perdriolle and clinical evaluation with scoliometer. We
      examined 42 adolescent idiopathic scoliosis (AIS) patients treated with posterior
      scoliosis surgery (PSS). The mean age at the time of surgery was 16 years. ICT
      evaluation was performed before and after scoliosis correction in prone position.
      Clinical rib hump measure with scoliometer and radiographic Perdriolle were
      performed before and after surgery. There was 71,5% of average rib hump
      correction with scoliometer but only 31% of correction with ICT (P=0,026) and
      there was no significant correlation between them (R=0,297, p=0,26). Mean
      postcorrectional Perdriolle AVR had a decrease of 16,5 degrees . The average ICT
      AVR had a decrease of only 1,2 degrees  (P=0,003). There was no significant
      statistic correlation between ICT and Perdriolle AVR evaluation (R=0,297, p=0,2).
      There is a significant discrepancy in AVR and rib hump assessment between
      scoliometer and Perdriolle methods and ICT evaluation, which seems to be the most
      accurate tool for spinal derotation measurement. 

PMID- 25861630
TI  - Intensive care medicine science: an art based on applied physiology?

PMID- 25861629
TI  - Epigenetic regulation in hepatocellular carcinoma requires long noncoding RNAs.
AB  - Recent evidence has proven the relevance of epigenetic changes in the development
      of hepatocellular carcinoma (HCC), the major adult liver malignancy. Moreover,
      HCC onset and progression correlate with the deregulation of several long
      noncoding RNAs (lncRNAs), exhibiting great biological significance. As discussed
      in this review, many of these transcripts are able to specifically act as tumor
      suppressors or oncogenes by means of their role as molecular platforms. Indeed,
      these lncRNAs are able to bind and recruit epigenetic modifiers on specific
      genomic loci, ultimately resulting in regulation of the gene expression relevant
      in cancer development. The evidence presented in this review highlights that
      lncRNAs-mediated epigenetic regulation should be taken into account for potential
      targeted therapeutic approaches. 

PMID- 25861631
TI  - The mechanism of melanocytes-specific cytotoxicity induced by phenol compounds
      having a prooxidant effect, relating to the appearance of leukoderma.
AB  - Specific phenol compounds including rhododendrol (RD), a skin-brightening
      ingredient in cosmetics, are reported to induce leukoderma, inducing a social
      problem, and the elucidation of mechanism of leukoderma is strongly demanded.
      This study investigated the relationship among the cytotoxicities of six phenol
      compounds on B16F10 melanoma cells and HaCaT keratinocytes and generated reactive
      oxygen species (ROS). As a result, the cytotoxicity of RD on B16F10 cells was
      higher than that on HaCaT cells, and RD significantly increased intracellular ROS
      and hydrogen peroxide (H2O2) levels in B16F10 cells. Furthermore, although
      raspberry ketone (RK), RD derivative, also increased intracellular ROS in B16F10
      cells, increase in ROS was suppressed by disodium dihydrogen
      ethylenediaminetetraacetate dehydrate (EDTA). The amounts of increased ROS with
      RK in HaCaT cells without melanocyte were further increased by tyrosinase.
      Therefore, tyrosinase, a metalloprotein having copper, was speculated to be one
      of causative agents allowing phenol compounds to work as a prooxidant. Hydroxyl
      radical was generated by adding a mixture of tyrosinase and H2O2 to RD, and the
      amount of the radical was further increased by UVB, indicating that RD
      cytotoxicity was caused by intracellularly increased ROS, which possibly related
      to phenol induced prooxidants. 

PMID- 25861632
TI  - Surgical results of retrograde mastoidectomy with primary reconstruction of the
      ear canal and mastoid cavity.
AB  - The aim of this study was to retrospectively review the long-term hearing results
      and the impact of mastoid exclusion/obliteration in patients with cholesteatoma
      (102 ears) who underwent retrograde tympanomastoidectomy and in whom bone
      chips/pate were applied as the sole materials during the procedure. In 79 ears,
      this was combined with ossiculoplasty in a single-stage procedure. In >71% of
      ears, the results of audiometric testing were monitored for more than 2 years.
      The results suggested there was a significant gain in hearing following surgery,
      with respect to the postoperative change in both air-conduction thresholds and
      air-bone gaps (P < 0.001). Linear regression analyses of pure-tone averages at
      different frequencies, before and after surgery, demonstrated that patients
      benefitted from a postoperative hearing gain at low and middle frequencies, but
      their hearing often deteriorated at frequencies of 8000 Hz. As for the impact of
      the type of tympanoplasty on hearing outcomes, type III-interposition markedly
      increased hearing gain. The overall rate of postoperative adverse events was
      8.8%. We conclude that reconstruction of the ear canal and mastoid via mastoid
      exclusion/obliteration using bone chips/pate can be considered as an alternative
      procedure following retrograde mastoidectomy. It gives excellent surgical results
      and has fewer postoperative adverse events. 

PMID- 25861633
TI  - Impact of depression, fatigue, and global measure of cortical volume on cognitive
      impairment in multiple sclerosis.
AB  - OBJECTIVE: To investigate the influence of demographic and clinical variables,
      such as depression, fatigue, and quantitative MRI marker on cognitive
      performances in a sample of patients affected by multiple sclerosis (MS).
      METHODS: 60 MS patients (52 relapsing remitting and 8 primary progressive)
      underwent neuropsychological assessments using Rao's Brief Repeatable Battery of
      Neuropsychological Tests (BRB-N), the Beck Depression Inventory-second edition
      (BDI-II), and the Fatigue Severity Scale (FSS). We performed magnetic resonance
      imaging to all subjects using a 3 T scanner and obtained tissue-specific volumes
      (normalized brain volume and cortical brain volume). We used Student's t-test to
      compare depressed and nondepressed MS patients. Finally, we performed a
      multivariate regression analysis in order to assess possible predictors of
      patients' cognitive outcome among demographic and clinical variables. RESULTS:
      27.12% of the sample (16/59) was cognitively impaired, especially in tasks
      requiring attention and information processing speed. From between group
      comparison, we find that depressed patients had worse performances on BRB-N
      score, greater disability and disease duration, and brain volume decrease.
      According to multiple regression analysis, the BDI-II score was a significant
      predictor for most of the neuropsychological tests. CONCLUSIONS: Our findings
      suggest that the presence of depressive symptoms is an important determinant of
      cognitive performance in MS patients.

PMID- 25861634
TI  - Antimicrobial activity of lactic acid bacteria in dairy products and gut: effect
      on pathogens.
AB  - The food industry seeks alternatives to satisfy consumer demands of safe foods
      with a long shelf-life able to maintain the nutritional and organoleptic quality.
      The application of antimicrobial compounds-producing protective cultures may
      provide an additional parameter of processing in order to improve the safety and
      ensure food quality, keeping or enhancing its sensorial characteristics. In
      addition, strong evidences suggest that certain probiotic strains can confer
      resistance against infection with enteric pathogens. Several mechanisms have been
      proposed to support this phenomenon, including antimicrobial compounds secreted
      by the probiotics, competitive exclusion, or stimulation of the immune system.
      Recent research has increasingly demonstrated the role of antimicrobial compounds
      as protective mechanism against intestinal pathogens and therefore certain
      strains could have an effect on both the food and the gut. In this aspect, the
      effects of the combination of different strains keep unknown. The development of
      multistrain probiotic dairy products with good technological properties and with
      improved characteristics to those shown by the individual strains, able to act
      not only as protective cultures in foods, but also as probiotics able to exert a
      protective action against infections, has gained increased interest. 

PMID- 25861635
TI  - Recombinant human thrombopoietin treatment promotes hematopoiesis recovery in
      patients with severe aplastic anemia receiving immunosuppressive therapy.
AB  - OBJECTIVE: To assess the effectiveness of recombinant human thrombopoietin
      (rhTPO) in severe aplastic anemia (SAA) patients receiving immunosuppressive
      therapy (IST). METHODS: Eighty-eight SAA patients receiving IST from January 2007
      to December 2012 were included in this retrospective analysis. Of these, 40
      subjects received rhTPO treatment (15000 U, subcutaneously, three times a week).
      rhTPO treatment was discontinued when the platelet count returned to normal
      range. Hematologic response, bone marrow megakaryocyte recovery, and time to
      transfusion independence were compared. RESULTS: Hematologic response was
      achieved in 42.5%, 62.5%, and 67.5% of patients receiving rhTPO and 22.9%, 41.6%,
      and 47.9% of patients not receiving rhTPO at 3, 6, and 9 months after treatment,
      respectively (P = 0.0665, P = 0.0579, and P = 0.0847, resp.). Subjects receiving
      rhTPO presented an elevated number of megakaryocytes at 3, 6, and 9 months when
      compared with those without treatment (P = 0.025, P = 0.021, and P = 0.011,
      resp.). The time to platelet and red blood cell transfusion independence was
      shorter in patients who received rhTPO than in those without rhTPO treatment.
      Overall survival rate presented no differences between the two groups.
      CONCLUSION: rhTPO could improve hematologic response and promote bone marrow
      recovery in SAA patients receiving IST.

PMID- 25861636
TI  - Natural antioxidant betanin protects rats from paraquat-induced acute lung injury
      interstitial pneumonia.
AB  - The effect of betanin on a rat paraquat-induced acute lung injury (ALI) model was
      investigated. Paraquat was injected intraperitoneally at a single dose of 20
      mg/kg body weight, and betanin (25 and 100 mg/kg/d) was orally administered 3
      days before and 2 days after paraquat administration. Rats were sacrificed 24
      hours after the last betanin dosage, and lung tissue and bronchoalveolar lavage
      fluid (BALF) were collected. In rats treated only with paraquat, extensive lung
      injury characteristic of ALI was observed, including histological changes,
      elevation of lung : body weight ratio, increased lung permeability, increased
      lung neutrophilia infiltration, increased malondialdehyde (MDA) and
      myeloperoxidase (MPO) activity, reduced superoxide dismutase (SOD) activity,
      reduced claudin-4 and zonula occluden-1 protein levels, increased BALF
      interleukin (IL-1) and tumor necrosis factor (TNF)-alpha levels, reduced BALF IL
      10 levels, and increased lung nuclear factor kappa (NF-kappaB) activity. In rats
      treated with betanin, paraquat-induced ALI was attenuated in a dose-dependent
      manner. In conclusion, our results indicate that betanin attenuates paraquat
      induced ALI possibly via antioxidant and anti-inflammatory mechanisms. Thus, the
      potential for using betanin as an auxilliary therapy for ALI should be explored
      further. 

PMID- 25861637
TI  - Effect of different germination conditions on antioxidative properties and
      bioactive compounds of germinated brown rice.
AB  - This study investigates antioxidative activity and bioactive compounds of
      ungerminated brown rice (UBR) and germinated brown rice (GBR). We used two rice
      cultivars (Oryza sativa L.), Taiwan Japonica 9 (TJ-9) and Taichung Indica 10 (TCI
      10), as the materials in our experiments. The conditions for inducing germination
      are soaking time in water 24, 48, or 72 h; temperature 26 or 36 degrees C;
      incubation in light or darkness; and open or closed vessels, in which the
      antioxidative activities and bioactive compounds of GBR were determined. We found
      that, in order to maximize antioxidative activity and bioactive compounds,
      germination should be under higher temperature (36 degrees C), long soaking time
      (72 h), darkness, and closed vessel. GBR contains much higher levels of
      antioxidative activity and bioactive compounds than ungerminated brown rice
      (UBR). We found a strong correlation between antioxidative activities (DPPH
      radical scavenging ability, reducing power, and Trolox equivalent antioxidant
      capacity) and bioactive compounds (gamma-oryzanols, tocopherol, and tocotrienol).
      Higher temperature (36 degrees C) is also conducive to the production of GABA in
      GBR. These results are considered very useful research references for the
      development of future functional foods and additives. 

PMID- 25861638
TI  - Evaluation of toxic, cytotoxic, mutagenic, and antimutagenic activities of
      natural and technical cashew nut shell liquids using the Allium cepa and Artemia
      salina bioassays.
AB  - The cashew nut releases a substance that is known as cashew nut shell liquid
      (CNSL). There are both natural (iCNSL) and technical (tCNSL) cashew nut shell
      liquids. This study used an Artemia salina bioassay to evaluate the toxic effects
      of iCNSL and tCNSL cashew nut shell liquids. It also evaluated the toxicity,
      cytotoxicity, and mutagenicity of CNSL and its effects on the damage induced by
      copper sulfate (CuSO4.5H2O) on the meristems' root of Allium cepa. Effects of the
      damage induced by CuSO4.5H2O were evaluated before (pre-), during (co-), and
      after (post-) treatments. The iCNSL contained 94.5% anacardic acid, and the tCNSL
      contained 91.3% cardanol. The liquids were toxic to A. salina. Toxicity,
      cytotoxicity, and mutagenicity were observed with iCNSL compared with the
      negative control. Similarly, iCNSL failed to inhibit the toxicity and
      cytotoxicity of CuSO4.5H2O. The tCNSL was not toxic, cytotoxic, or mutagenic in
      any of the concentrations. However, the lowest iCNSL concentrations and all of
      the tCNSL concentrations had preventive, antimutagenic, and reparative effects on
      micronuclei and on chromosomal aberrations in the A. cepa. Therefore, protective,
      modulating, and reparative effects may be observed in the A. cepa, depending on
      the concentration and type of CNSL used. 

PMID- 25861639
TI  - Evaluation of the inflammatory response in macrophages stimulated with exosomes
      secreted by Mycobacterium avium-infected macrophages.
AB  - Exosomes secreted from Mycobacterium avium-infected macrophages contain numerous
      antigens of both M. avium and the host cell and are involved in the induction and
      expression of the inflammatory responses in macrophages. The interaction between
      exosomes secreted from M. avium-infected macrophages and macrophage phagocytosis,
      cytokine secretion, immunostimulation, and apoptosis was analyzed. Upon
      stimulation with exosomes secreted from M. avium-infected macrophages, the
      phagocytosis of dextran by treated macrophages was increased. Furthermore, the
      expression of CD40, CD80, CD81, CD86, HLA-DR, and most notably CD195 was
      enhanced. Additionally, the secretion of IL-6, IL-8, IL-10, IFN-gamma, and TNF
      alpha was increased by stimulated macrophages. Exosome stimulation did not induce
      macrophage apoptosis when compared with macrophages infected with M. avium.
      Caspase expression, including that of caspases 3, 6, and 8, was also not altered
      in exosome stimulated macrophages. Thus exosomes trigger the inflammatory
      response in macrophages owing to the presence of bacterial antigens but have no
      effect on macrophage viability. 

PMID- 25861642
TI  - Control of autophagy in cancer.

PMID- 25861640
TI  - Improvement of endurance of DMD animal model using natural polyphenols.
AB  - Duchenne muscular dystrophy (DMD), the most common form of muscular dystrophy, is
      characterized by muscular wasting caused by dystrophin deficiency that ultimately
      ends in force reduction and premature death. In addition to primary genetic
      defect, several mechanisms contribute to DMD pathogenesis. Recently, antioxidant
      supplementation was shown to be effective in the treatment of multiple diseases
      including muscular dystrophy. Different mechanisms were hypothesized such as
      reduced hydroxyl radicals, nuclear factor-kappaB deactivation, and NO protection
      from inactivation. Following these promising evidences, we investigated the
      effect of the administration of a mix of dietary natural polyphenols (ProAbe) on
      dystrophic mdx mice in terms of muscular architecture and functionality. We
      observed a reduction of muscle fibrosis deposition and myofiber necrosis together
      with an amelioration of vascularization. More importantly, the recovery of the
      morphological features of dystrophic muscle leads to an improvement of the
      endurance of treated dystrophic mice. Our data confirmed that ProAbe-based diet
      may represent a strategy to coadjuvate the treatment of DMD. 

PMID- 25861641
TI  - Factors influencing the eicosanoids synthesis in vivo.
AB  - External factors activate a sequence of reactions involving the reception,
      transduction, and transmission of signals to effector cells. There are two main
      phases of the body's reaction to harmful factors: the first aims to neutralize
      the harmful factor, while in the second the inflammatory process is reduced in
      size and resolved. Secondary messengers such as eicosanoids are active in both
      phases. The discovery of lipoxins and epi-lipoxins demonstrated that not all
      arachidonic acid (AA) derivatives have proinflammatory activity. It was also
      revealed that metabolites of eicosapentaenoic acid (EPA) and docosahexaenoic acid
      (DHA) such as resolvins, protectins, and maresins also take part in the
      resolution of inflammation. Knowledge of the above properties has stimulated
      several clinical trials on the influence of EPA and DHA supplementation on
      various diseases. However, the equivocal results of those trials prevent the
      formulation of guidelines on EPA and DHA supplementation. Prescription drugs are
      among the substances with the strongest influence on the profile and quantity of
      the synthesized eicosanoids. The lack of knowledge about their influence on the
      conversion of EPA and DHA into eicosanoids may lead to erroneous conclusions from
      clinical trials. 

PMID- 25861643
TI  - Andrographolide suppresses proliferation of nasopharyngeal carcinoma cells via
      attenuating NF-kappaB pathway.
AB  - Andrographolide (Andro) has been reported to have anticancer activity in multiple
      types of cancer due to its capacity to inactivate NF-kappaB pathway. Previous
      studies showed the therapeutic potential of targeting NF-kappaB pathway in
      nasopharyngeal carcinoma (NPC). However, the anticancer activity of Andro in NPC
      has not been reported. In this study, we defined the anticancer effects of Andro
      in NPC and elucidated its potential mechanisms of action. Our results showed that
      Andro significantly inhibited the proliferation and invasion of NPC cells (P <
      0.05, resp.). These anticancer activities were associated with cell apoptosis,
      cell death and induction of cell cycle arrest, and the downregulation of NF
      kappaB target genes. This work provides evidence that NF-kappaB pathway is a
      potential therapeutic target and may also be indispensable in the Andro-mediated
      anticancer activities in nasopharyngeal carcinoma. 

PMID- 25861644
TI  - Discover the molecular biomarker associated with cell death and extracellular
      matrix module in ovarian cancer.
AB  - High throughput technologies have provided many new research methods for ovarian
      cancer investigation. In tradition, in order to find the underlying functional
      mechanisms of the survival-associated genes, gene sets enrichment analysis (GSEA)
      is always regarded as the important choice. However, GSEA produces too many
      candidate genes and cannot discover the signaling transduction cascades. In this
      work, we have used a network-based strategy to optimize the discovery of
      biomarkers using multifactorial data, including patient expression, clinical
      survival, and protein-protein interaction (PPI) data. The biomarkers discovered
      by this strategy belong to the network-based biomarker, which is apt to reveal
      the underlying functional mechanisms of the biomarker. In this work, over 400
      expression arrays in ovarian cancer have been analyzed: the results showed that
      cell death and extracellular module are the main themes related to ovarian cancer
      progression. 

PMID- 25861645
TI  - Comment on "Clinical comparisons of two free light chain assays to immunofixation
      electrophoresis for detecting monoclonal gammopathy".

PMID- 25861646
TI  - Corrigendum to "Regional anesthesia for postoperative pain control".

PMID- 25861648
TI  - Enhanced cardiovascular risk in rheumatoid arthritis: elucidation, assessment,
      and management.

PMID- 25861647
TI  - Feasibility of bioelectrical impedance spectroscopy measurement before and after
      thoracentesis.
AB  - BACKGROUND: Bioelectrical impedance spectroscopy is applied to measure changes in
      tissue composition. The aim of this study was to evaluate its feasibility in
      measuring the fluid shift after thoracentesis in patients with pleural effusion.
      METHODS: 45 participants (21 with pleural effusion and 24 healthy subjects) were
      included. Bioelectrical impedance was analyzed for "Transthoracic," "Foot to
      Foot," "Foot to Hand," and "Hand to Hand" vectors in low and high frequency
      domain before and after thoracentesis. Healthy subjects were measured at a single
      time point. RESULTS: The mean volume of removed pleural effusion was 1169 +/- 513
      mL. The "Foot to Foot," "Hand to Hand," and "Foot to Hand" vector indicated a
      trend for increased bioelectrical impedance after thoracentesis. Values for the
      low frequency domain in the "Transthoracic" vector increased significantly (P <
      0.001). A moderate correlation was observed between the amount of removed fluid
      and impedance change in the low frequency domain using the "Foot to Hand" vector
      (r = -0.7). CONCLUSION: Bioelectrical impedance changes in correlation with the
      thoracic fluid level. It was feasible to monitor significant fluid shifts and
      loss after thoracentesis in the "Transthoracic" vector by means of bioelectrical
      impedance spectroscopy. The trial is registered with Registration Numbers IRB
      EK206/11 and NCT01778270.

PMID- 25861649
TI  - Delivery of antibiotics from cementless titanium-alloy cubes may be a novel way
      to control postoperative infections.
AB  - Bacterial colonisation and biofilm formation onto orthopaedic devices are
      difficult to eradicate. In most cases infection is treated by surgical removal of
      the implant and cleaning of the infected area, followed by extensive treatment
      with broad-spectrum antibiotics. Such treatment causes great discomfort, is
      expensive, and is not always successful. In this study we report on the release
      of vancomycin through polyethersulfone membranes from channels in cementless
      titanium-alloy cubes. The cubes were constructed with LaserCUSING from Ti6Al4V
      ELI powder. Vancomycin was released by non-Fickian anomalous (constraint)
      diffusion. Approximately 50% of the vancomycin was released within the first 17
      h. However, sustained delivery of vancomycin for 100 h was possible by
      reinjecting the channels. Refillable implants may be a novel way to control
      postoperative infections. 

PMID- 25861651
TI  - Microwave assisted synthesis, antifungal activity, and DFT study of some novel
      triazolinone derivatives.
AB  - A series of some novel 1,2,4-triazol-5(4H)-one derivatives were designed and
      synthesized under microwave irradiation via multistep reaction. The structures of
      1,2,4-triazoles were confirmed by (1)H NMR, MS, FTIR, and elemental analysis. The
      antifungal activities of 1,2,4-triazoles were determined. The antifungal activity
      results indicated that the compounds 5c, 5f, and 5h exhibited good activity
      against Pythium ultimum, and the compounds 5b and 5c displayed good activity
      against Corynespora cassiicola. Theoretical calculation of the compound 5c was
      carried out with B3LYP/6-31G (d). The full geometry optimization was carried out
      using 6-31G(d) basis set, and the frontier orbital energy and electrostatic
      potential were discussed, and the structure-activity relationship was also
      studied. 

PMID- 25861650
TI  - Biotechnological and agronomic potential of endophytic pink-pigmented
      methylotrophic Methylobacterium spp.
AB  - The genus Methylobacterium is composed of pink-pigmented facultative
      methylotrophic (PPFM) bacteria, which are able to synthesize carotenoids and grow
      on reduced organic compounds containing one carbon (C1), such as methanol and
      methylamine. Due to their high phenotypic plasticity, these bacteria are able to
      colonize different habitats, such as soil, water, and sediment, and different
      host plants as both endophytes and epiphytes. In plant colonization, the
      frequency and distribution may be influenced by plant genotype or by interactions
      with other associated microorganisms, which may result in increasing plant
      fitness. In this review, different aspects of interactions with the host plant
      are discussed, including their capacity to fix nitrogen, nodule the host plant,
      produce cytokinins, auxin and enzymes involved in the induction of systemic
      resistance, such as pectinase and cellulase, and therefore plant growth
      promotion. In addition, bacteria belonging to this group can be used to reduce
      environmental contamination because they are able to degrade toxic compounds,
      tolerate high heavy metal concentrations, and increase plant tolerance to these
      compounds. Moreover, genome sequencing and omics approaches have revealed genes
      related to plant-bacteria interactions that may be important for developing
      strains able to promote plant growth and protection against phytopathogens. 

PMID- 25861652
TI  - Focus on diffusion MR investigations of musculoskeletal tissue to improve
      osteoporosis diagnosis: a brief practical review.
AB  - Nowadays, a huge number of papers have documented the ability of diffusion
      magnetic resonance imaging (D-MRI) to highlight normal and pathological
      conditions in a variety of cerebral, abdominal, and cardiovascular applications.
      To date, however, the role of D-MRI to investigate musculoskeletal tissue,
      specifically the cancellous bone, has not been extensively explored. In order to
      determine potentially useful applications of diffusion techniques in
      musculoskeletal investigation, D-MRI applications to detect osteoporosis disease
      were reviewed and further explained. 

PMID- 25861653
TI  - IFN-CSP inhibiting hepatitis B virus in HepG2.2.15 cells involves JAK-STAT signal
      pathway.
AB  - Frequent and high-dose administration of interferon to patients with viral
      hepatitis results in various side effects. In our previous study, a novel liver
      targeting interferon (IFN-CSP) combining Plasmodium region I peptide with
      IFNalpha2b was successfully designed and expressed in the Escherichia coli
      expression systems. This targeting would target the IFNalpha2b specifically to
      the liver, thus reducing the adverse events. In the present study, we further
      investigated the anti-HBV effects and molecular mechanisms of recombinant IFN-CSP
      in HepG2.2.15 cell line. Hepatitis B surface antigen (HBsAg) and HBe antigen
      (HBeAg) in the culture supernatants were analyzed by enzyme-linked immunosorbent
      assay (ELISA). HBV-DNA was measured by real-time quantitative PCR. HBV core
      protein was assayed by immunofluorescent and western blot analysis. The
      expressions of signal transducers and transactivator 1 (STAT1), STAT2, IFN
      regulatory factor 9 (IRF-9), and 2'-5'-oligoadenylate synthetase 1 (OAS1) were
      investigated by the reverse transcription PCR and western blot analysis. Results
      indicate IFN-CSP efficiently inhibited HBsAg and HBeAg secretion, HBV-DNA
      replication, and HBV core protein expression in HepG2.2.15 cells. The anti-HBV
      mechanisms involve activation of JAK-STAT signaling and increase of the anti-HBV
      protein OAS expression. IFN-CSP could be a good substitute for IFNalpha2b for
      anti-HBV treatment. 

PMID- 25861654
TI  - Impact of umbilical cord blood-derived mesenchymal stem cells on cardiovascular
      research.
AB  - Over the years, cell therapy has become an exciting opportunity to treat human
      diseases. Early enthusiasm using adult stem cell sources has been tempered in
      light of preliminary benefits in patients. Considerable efforts have been
      dedicated, therefore, to explore alternative cells such as those extracted from
      umbilical cord blood (UCB). In line, UCB banking has become a popular possibility
      to preserve potentially life-saving cells that are usually discarded after birth,
      and the number of UCB banks has grown worldwide. Thus, a brief overview on the
      categories of UCB banks as well as the properties, challenges, and impact of UCB
      derived mesenchymal stem cells (MSCs) on the area of cardiovascular research is
      presented. Taken together, the experience recounted here shows that UCBMSCs are
      envisioned as attractive therapeutic candidates against human disorders arising
      and/or progressing with vascular deficit. 

PMID- 25861655
TI  - Protective effects of scutellarin on type II diabetes mellitus-induced testicular
      damages related to reactive oxygen species/Bcl-2/Bax and reactive oxygen
      species/microcirculation/staving pathway in diabetic rat.
AB  - The goal of our study is to evaluate the effect of Scutellarin on type II
      diabetes-induced testicular disorder and show the mechanism of Scutellarin's
      action. We used streptozotocin and high-fat diet to establish type II diabetic
      rat model. TUNEL and haematoxylin and eosin staining were used to evaluate the
      testicular apoptotic cells and morphologic changes. Immunohistochemical staining
      was used to measure the expression level of vascular endothelial growth factor
      and blood vessel density in testes. Oxidative stress in testes and epididymis was
      tested by fluorescence spectrophotometer and ELISA. The expression of Bcl-2/Bax
      and blood flow rate in testicular vessels were measured by western blot and
      Doppler. Our results for the first time showed that hyperglycemia induced
      apoptotic cells and morphologic impairments in testes of rats, while
      administration of Scutellarin can significantly inhibit these damages. This
      effect of Scutellarin is controlled by two apoptotic triggers: ROS/Bcl-2/Bax and
      ROS/microcirculation/starving pathway. 

PMID- 25861656
TI  - HIV vaccine research: the challenge and the way forward.
AB  - Human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) is a
      worldwide epidemic, with over 35 million people infected currently. Therefore,
      the development of a safe and effective HIV-1 vaccine is on top of the global
      health priority. In the past few years, there have been many promising advances
      in the prevention of HIV/AIDS, among which the RV144 Thai trial has been
      encouraging and suggests optimization of the current vaccine strategies or search
      for novel strategies. Here we reviewed the brief history of HIV-1 vaccine,
      analyzed key challenges existing now, and illustrated future research
      priority/directions for a therapeutic or prophylactic HIV-1 vaccine, with the
      hope of accelerating the speed of vaccine development. We believe that an
      effective HIV-1 vaccine, together with other prevention approaches, will bring an
      end to this epidemic in the near future. 

PMID- 25861657
TI  - Worksite health promotion programs in college settings.
AB  - The purpose of this paper is to describe the multifaceted nature and benefits of
      worksite health promotion programs (WHPPs), with emphasis on the college setting.
      An assessment of the peer-reviewed literature was conducted of articles published
      since 2000. Several search engines were accessed and selected key words were
      used. Most studies examining WHPPs have focused on return on investment and
      productivity. Research that targets the softer side-benefits of health promotion
      programs in the workplace is less available. Although the college setting offers
      some advantages for implementing health promotion programs. They may also have
      unique challenges due to their large and diverse employee population. There is
      little research to show the effectiveness and unique challenges of college-based
      health promotion programs. 

PMID- 25861658
TI  - An empowering approach to promote the quality of life and self-management among
      type 2 diabetic patients.
AB  - Type 2 diabetes is one of the most serious health concerns and policy agendas
      around the world. Epidemiological evidence suggests that it will likely continue
      to increase globally. Diabetes is strongly associated with the patients'
      unhealthy lifestyle and behavioral patterns and socio-economic changes. New model
      of thinking is required to recognize whether the patients are in control of and
      responsible for the daily self-management of diabetes. Such a new approach should
      be based on 'empowerment and involvement' to be more applicable to daily
      activities in diabetic patients. Rapid changes toward patient empowerment and
      increasing involvement of patients in their care plan indicate more emphasis on
      disease prevention and health promotion and education than on mere disease and
      its treatment. Such changes make a step toward pervasive sense of responsibility
      among patients about their illness for their daily activities. Using the
      empowerment approach, healthcare professionals would help patients make informed
      decisions in accordance with their particular circumstances. Patient empowerment
      implies a patient-centered, collaborative approach that helps patients determine
      and develop the inherent capacity to be responsible for their own life.
      Empowerment is something more than certain health behaviors. Empowerment is more
      than an intervention, technique or strategy. It is rather a vision that helps
      people change their behavior and make decisions about their health care. It has
      the potential to improve the overall health and well-being of individuals and
      communities, and to change the socio-environmental factors that cause poor health
      conditions. The main concept of this change is the tendency to change. 

PMID- 25861659
TI  - Investigating the root causes of duplicate publication in research articles.
AB  - Duplicate publication is the republication of an article in which a lot of
      important parts overlap with the published copy. This issue is nearly at the top
      of the list of subjects, which medical journal editors discuss. this study was
      conducted with the purpose of investigating the publication patterns and
      determining it's root causes in research articles in the Isfahan University of
      Medical Science and to find a solution to prevent it. In a cross sectional study,
      All the discovered cases of duplicate publication, which were referred to the
      ethics committee of the Isfahan University of Medical Science during 2005-2008
      were selected to be investigated through a descriptive method. After confirmation
      about the case of a duplicate publication, the requisite investigation was
      conducted through interviews and review of the correspondence and documentaries,
      and then, a radical line was charted. After investigating the cases and
      classifying the radical causes and incidents, categorization and definition of
      duplicate publication are presented. Eight out of nine republished articles
      belonged to the first category of Baily's index (copy publication) and one was in
      the third category (minimum publishable unit: Salami slicing). The results of the
      present article indicate that, the scientific community of the country is not yet
      familiar with the professional principles of scientific and research affairs.
      According to the results of this investigation, it is recommended to take
      official action against duplicate publication cases, violation of copyright, and
      also to have strict instructions against this unethical practice. 

PMID- 25861660
TI  - Study of relationship between the organizational structure and market orientation
      from the viewpoint of nurse managers.
AB  - BACKGROUND: Considering globalization of health care and quality improvement
      trend to respond to competition and customer orientation, attention to
      organizational structure and its relationship with market orientation is
      essential. Therefore, this study reviews the relationship between organizational
      structure and market orientation in selected hospitals of Isfahan (Iran).
      MATERIALS AND METHODS: This study was a descriptive survey. The study population
      comprised nurse managers from selected hospitals (n = 80). Data collection tools
      were two questionnaires (market orientation questionnaire and organizational
      structure) that the validity and reliability were confirmed (r = 0.83 for market
      orientation questionnaire and r = 0.87 for organizational structure). SPSS (Ver.
      16) software was used for the analyses. RESULTS: The mean score of organizational
      structure was 65.4 (11.2) and total mean of market orientation was 51.14 (17.6).
      All aspects of the organizational structure (Organization Centralization,
      Formalization in Organization, and Organization Complication) and market
      orientation (responding to competition, accountability, customer satisfaction,
      intelligent organization)-except by responding to clients with Formalization in
      Organization-as well as all aspects of the Systemic attitude (the system of
      internal coordination and communication systems_ and market orientation
      (responding to competition, accountability, customer satisfaction, intelligent
      organization), there was a meaningful relationship (P < 0.05). CONCLUSION: Market
      orientation and its dimensions have a significant relationship with
      organizational structure and can lead managers' view to the analysis and
      recognizing elements of success and achievement to goals. With increasing
      competition in markets, globalization of health services, and presence in
      international markets and more attention to patients' satisfaction, hospitals
      need to understand and use of market orientation in order to promote quality and
      services in the health care system.

PMID- 25861661
TI  - Job strain (demands and control model) as a predictor of cardiovascular risk
      factors among petrochemical personnel.
AB  - BACKGROUND: One of the practical models for the assessment of stressful working
      conditions due to job strain is job demand and control model, which explains how
      physical and psychological adverse consequences, including cardiovascular risk
      factors can be established due to high work demands (the amount of workload, in
      addition to time limitations to complete that work) and low control of the worker
      on his/her work (lack of decision making) in the workplace. The aim of this study
      was to investigate how certain cardiovascular risk factors (including body mass
      index [BMI], heart rate, blood pressure, cholesterol and smoking) and the job
      demand and job control are related to each other. MATERIALS AND METHODS: This
      prospective cohort study was conducted on 500 workers of the petrochemical
      industry in south of Iran, 2009. The study population was selected using simple
      random statistical method. They completed job demand and control questionnaire.
      The cardiovascular risk factors data was extracted from the workers hygiene
      profiles. Chi-square (chi (2)) test and hypothesis test (eta) were used to assess
      the possible relationship between different quantified variables, individual
      demographic and cardiovascular risk factors. RESULTS: The results of this study
      revealed that a significant relationship can be found between job demand control
      model and cardiovascular risk factors. Chi-square test result for the heart rate
      showed the highest (chi (2) = 145.078) relationship, the corresponding results
      for smoking and BMI were chi (2) = 85.652 and chi (2) = 30.941, respectively.
      Subsequently, hypothesis testing results for cholesterol and hypertension was
      0.469 and 0.684, respectively. DISCUSSION: Job strain is likely to be associated
      with an increased risk of cardiovascular risk factors among male staff in a
      petrochemical company in Iran. The parameters illustrated in the Job demands and
      control model can act as acceptable predictors for the probability of job stress
      occurrence followed by showing a high trend of CVD risk factors.

PMID- 25861662
TI  - Prevalence of obesity and behaviors associated with the development of metabolic
      disease among medical practitioners in Jordan.
AB  - BACKGROUND: The health status of medical practitioners can potentially impact
      their ability to counsel patients. The purpose of the study was to examine the
      prevalence of obesity and behaviors associated with the development of metabolic
      disease among medical practitioners in the country of Jordan. MATERIALS AND
      METHODS: The participants were 748 (male n = 285, 32.3 years +/- 7.3, female n =
      463, 29.7 years +/- 5.7) randomly selected pharmacists, nurses, physicians,
      medical lab technicians, and radiation specialists from a variety of medical
      institutions in Jordan. A short 25-item validated instrument was chosen for this
      investigation. After the survey was administered and data were tabulated, one-way
      analysis of variance and Pearson's Chi-square analysis were conducted to examine
      differences in reported risk behaviors (low physical activity [PA], smoking) and
      obesity by gender, age and medical specialty. RESULTS: Descriptive analysis
      revealed that 20.9% of the participants self-reported as smokers of cigarettes,
      47.9% were either overweight or obese, and 52.9% reported no days of planned PA
      on average per week. The results suggested a difference in body mass index (BMI)
      classification (F = 17.9, P <= 0.001) and smoking (F = 5.33, P = 0.021) by age.
      Mean age associated with being underweight was 26.4 years for normal weight 29.3
      years for overweight 31.6 years and finally for obese was 34.5 years. Chi-square
      test resulted in differences by gender (chi(2) > 50, P <= 0.001) for BMI (males:
      26.4 +/- 3.7; females: 24.6 +/- 3.7), PA (males no planned PA 61.1%, females
      47.9%) and smoking (males 43.1% smokers, females 7.1%). Researchers discovered
      that medical specialty was related to differences in reported smoking (chi(2) =
      26.5, P <= 0.001) and days of planned PA (chi(2) = 24.2, P = 0.019). CONCLUSIONS:
      Within the population of medical practitioners there is still a high incidence of
      obesity and risk behaviors associated with metabolic diseases. It also appears
      that these incidence rates are greater among men, with increasing age, and among
      certain medical specialties.

PMID- 25861663
TI  - Life experiences in heart transplant recipients.
AB  - INTRODUCTION: Heart transplantation is considered as a golden standard of
      treatment for advanced heart failure. After - transplantation health of patients
      is influenced by numerous issues which many of them are unknown to the treatment
      team including nurses. This research - with the aim of describing the life
      experiences of heart transplant patients - help us to get close to the patients
      private life and gain comprehensive and a general understanding of all aspects of
      their life. METHODS: This study applied qualitative approach using phenomenology
      method. The purposive sampling was conducted and continued with 9 participants
      until information reached saturation point. The participants are the heart
      transplant recipients who had surgery in Esfahan's Heart Surgery Center of Shahid
      Chamran. RESULTS: The extracted interviews were analyzed through Colaizzi method:
      The eleven extracted main concepts were included: Belief, tendencies of the
      recipient and family of donor, bewilderment, moment of facing with
      transplantation, satisfaction, vital organ, support, temperament, physical
      effects of transplantation, mental changes, paradox of life and death.
      CONCLUSION: In heart transplant patients, being in touch with peers and family
      support have an important role in putting up with the transplantation issue. Lack
      of social situation and social support were among the patients distresses. Lack
      of the necessary information about transplantation made patients dissatisfied
      with the heart transplantation. Regarding the research findings, training
      received by patients would not be suffice and lack of information has been made
      them face with problems; therefore, the nurse team of transplantation should play
      more an active role in training the patients.

PMID- 25861664
TI  - Preparation and evaluation of information leaflet for tobacco users.
AB  - BACKGROUND: There is general lack of knowledge concerning the sings, symptoms,
      and risk factors of oral cancer in the general population, particularly among
      tobacco users. A challenging measure for the health care professions is to
      improve patients' knowledge about the causes and signs of oral cancer and, more
      importantly, to modify their health behaviors. The most frequent approach used to
      achieve this is production of leaflet. The aim of this study was to outline and
      carry out the steps involved in the production of information leaflet for tobacco
      users and its evaluation. MATERIALS AND METHODS: The existing materials on
      tobacco and its ill effects were reviewed. Leaflets were prepared based on the
      European Commission Guidelines for patient information leaflet and information
      packages. Subject experts reviewed the content of leaflet. Content validity was
      checked using Lawshe method. Reliability was checked using Flesch formula.
      RESULTS: Content Validity Ratio (CVR) value was 0.99, which was acceptable. The
      reliability of the final wording of the leaflet was 80, which was classified as
      "fairly ease." CONCLUSION: The leaflet could be used as a health education aid to
      motivate tobacco users to quit tobacco use.

PMID- 25861665
TI  - Awareness of palliative care among doctors of various departments in all four
      teaching medical colleges in a metropolitan city in Eastern India: A survey.
AB  - OBJECTIVE: To enquire about the level of awareness regarding various important
      aspects of palliative medicine among doctors of various departments in four
      Medical Colleges in Kolkata through a questionnaire. MATERIALS AND METHODS: A
      questionnaire was developed by few members of Indian Association of Palliative
      Care. It was distributed, to a convenience sample of doctors who worked at
      various departments in all four teaching hospitals in Kolkata. The distribution
      and collection of questionnaires was carried out within four months. RESULTS: The
      results suggested that 85% of the doctors felt that cancer was the commonest
      reason for the palliative care teams to be involved. Seventy four percent of the
      doctors mentioned that pain control was their prime job; 53% said that they are
      enjoying their encounter with palliative care, so far; 77% of the doctors thought
      breaking bad news is necessary in further decision making process; only 22% of
      the doctors reported the WHO ladder of pain control sequentially, 35% of the
      doctors believed other forms of therapies are useful in relieving pain, 35% of
      the doctors thought that they gave enough importance and time for pain control;
      77% said that they had heard about a hospice, among them still 61% of the doctors
      thought that the patients should spend last days of their life at home. Thinking
      of the future, 92% of the doctors think that more and more people will need
      palliative care in the coming days. CONCLUSION: Amongst the doctors of various
      departments, there is a lack of training and awareness in palliative care. Almost
      all the doctors are interested and they are willing to have more training in pain
      control, breaking bad news, communication skills and terminal care.

PMID- 25861666
TI  - The impact of teaching experience on interview performance of different
      candidates of basic medical sciences in PhD admission.
AB  - BACKGROUND: Admission includes written and interview at universities belonging to
      the ministry of the health and medical education of Iran at PhD level. In the
      present work, it was tried to find out the likelihood of interview performance of
      different candidates with their teaching experience in Iranian national medical
      PhD admission in the year 1386-87. METHODS AND MATERIALS: In this study,
      applicants' exam results were extracted from their score workbooks for year 86
      87. PhD applicants' categories were public (ordinary) and employed lecturers.
      Invited numbers of candidates for interview were 556 from 29 different fields of
      study. As the number of written subjects were not the same within different
      fields of study, at the first, each group score distribution were normalized to
      one and then combined together for final consideration. RESULTS: Accept and
      reject percentage within public applicants were 45.1 and 54.9, respectively,
      while the accept percentage within lecturer applicants was 66 and the reject was
      34 respectively. Scores of all 29 groups were combined after normalization. The
      overall performance including test plus interview for public and lecturers were
      1.02 +/- 0.12 and 0.95 +/- 0.1, respectively. The average and standard deviation
      of test exam of public and lecturer were 1.04 +/- 0.16 and 0.91 +/- 0.12,
      respectively. The average and standard deviation of interview exam of public
      applicants and lecturers applicants were 0.98 +/- 0.18 and 1.04 +/- 0.17,
      respectively. CONCLUSION: As results show, the interview performance of lecturers
      is better than public applicants. Unbalanced acceptance rate amongst lecturers
      was increased due to the hold of reservation toward interview and due to their
      higher results gain during interview. If the test performance was a reliable
      measure for viability of applicant, this reservation would change the acceptance
      rate close to balance.

PMID- 25861667
TI  - Atomic force microscopy crosslinks interdisciplinary eye research.

PMID- 25861668
TI  - Is laser photocoagulation treatment currently useful in diabetic macular edema?

PMID- 25861669
TI  - Corneal topography with upper eyelid platinum chain implantation using the
      pretarsal fixation technique.
AB  - PURPOSE: To determine the effect of upper eyelid platinum chain implantation,
      with the pretarsal fixation technique, on corneal astigmatism. METHODS: This is a
      prospective, cohort study. Fifteen eyes of 15 patients underwent upper eyelid
      platinum chain implantation, with the pretarsal fixation technique, for facial
      nerve palsy. Information recorded included patient demographics, etiology for
      facial palsy, weight of the implant, time from onset of paresis to upper eyelid
      platinum chain implantation, associated surgical procedures, and preoperative and
      postoperative corneal topography measurements. RESULTS: Of the 15 patients
      studied, 10 were male and five were female. The mean age was 55.9 +/- 13.8 years
      (range, 33-87 years). The most common etiology for facial palsy was acoustic
      neuroma. The weight of the implant ranged from 0.6 to 1.6gr (median 1.2gr). The
      time from onset of paresis to upper eyelid platinum chain implantation varied
      from 1 week to 3 months (median 1 month). Four patients had an associated
      procedure to correct the effect of paralytic ectropion. There was no
      statistically significant difference in with the rule astigmatism before and
      after platinum chain implantation. CONCLUSIONS: Upper eyelid platinum chain
      implantation, with the pretarsal fixation technique, does not appear to cause
      significant change in corneal astigmatism. This is contrary to data for pretarsal
      gold weight implantation, which does induce significant with the rule
      astigmatism.

PMID- 25861670
TI  - Lagophthalmos and frozen globe as the initial presentation of invasive breast
      carcinoma.
AB  - A 75-year-old woman presented with six months history of progressing
      lagophthalmos and immobility of the left eye. Magnetic resonance imaging (MRI) of
      the orbit demonstrated infiltration of orbital fat and the extra-ocular muscles.
      We performed transverse blepharotomy of the left eyelid to correct lagophthalmos;
      and during surgery, we took a biopsy sample from levator muscle and orbital fat.
      After the operation, the patient was able to close her eyelids, and epithelial
      problems were resolved. Biopsy revealed fibro-vascular, muscle and fat tissue
      infiltrated with minimally differentiated carcinoma cells. Breast examination
      revealed a nodule in the left breast. Biopsy of the mass confirmed the diagnosis
      of invasive breast carcinoma. Orbital manifestation of metastases, such as
      diplopia, lagophthalmos or pain may reduce life quality of the patients and must
      be evaluated on a multidisciplinary basis. 

PMID- 25861672
TI  - Incidence of vertical phoria on postural control during binocular vision: what
      perspective for prevention to nonspecific chronic pain management?
AB  - Vertical heterophoria (VH) is the latent vertical misalignment of the eyes when
      the retinal images are dissociated, vertical orthophoria (VO) when there is no
      misalignment. Studies on postural control, during binocular vision in upright
      stance, reported that healthy subjects with small VH vs. VO are less stable, but
      the experimental cancellation of VH with an appropriate prism improves postural
      stability. The same behavior was recorded in nonspecific chronic back pain
      subjects, all with VH. It was hypothesized that, without refraction problems, VH
      indicates a perturbation of the somaesthetic cues required in the sensorimotor
      loops involved in postural control and the capacity of the CNS to optimally
      integrate these cues, suggesting prevention possibilities. Sensorimotor conflict
      can induce pain and modify sensory perception in some healthy subjects; some
      nonspecific pain or chronic pain could result from such prolonged conflict in
      which VH could be a sign, with new theoretical and clinical implications. 

PMID- 25861671
TI  - ERK5 Mediated Signalling in Diabetic Retinopathy.
AB  - Diabetic retinopathy is the lead among causes of blindness in North America.
      Glucose-induced endothelial injury is the most important cause of diabetic
      retinopathy and other vascular complications. Extracellular signal-regulated
      kinase 5 (ERK5), also known as big mitogen-activated protein kinase 1 (BMK1), is
      a member of mitogen-activated protein kinases (MAPK) family. Physiologically, it
      is critical for cardiovascular development and maintenance of the endothelial
      cell integrity. Extracellular signal-regulated kinase 5 is protective for
      endothelial cells under stimulation and stress. Decreased activation of ERK5
      results in increased endothelial cell death. Extracellular signal-regulated
      kinase 5 signaling may be subject to alteration by hyperglycemia, while signaling
      pathway including ERK5 may be subject to alteration during pathogenesis of
      diabetic complications. In this review, the role of ERK5 in diabetic macro- and
      microvascular complications with a focus on diabetic retinopathy are summarized
      and discussed. 

PMID- 25861673
TI  - Reliability and validity of the Thai version of the Florida Obsessive-Compulsive
      Inventory.
AB  - This study aimed to examine the reliability and validity of the Thai version of
      the FOCI (FOCI-T), which is a brief self-report questionnaire to assess the
      symptoms and severity of obsessive-compulsive disorder (OCD). Forty-seven OCD
      patients completed the FOCI-T, the Patient Health Questionnaire (PHQ-9), and the
      Pictorial Thai Quality of Life (PTQL). They were then interviewed to determine
      the OCD symptom severity by the Yale-Brown Obsessive-Compulsive Scale-Second
      Edition (YBOCS-II) and depressive symptoms by the Hamilton Rating Scale for
      Depression (HAM-D), together with the Global Assessment of Functioning (GAF) and
      the Clinical Global Impression-Severity Scales (CGI-S). The result showed that
      the FOCI-T had satisfactory internal consistency reliability on both the Symptom
      Checklist (KR-20=0.86) and the Severity Scale (alpha=0.92). Regarding validity
      analyses, the FOCI-T Severity Scale had stronger correlations with the YBOCS-II
      and CGI-S than the FOCI-T Symptom Checklist. This implied the independence
      between the FOCI-T Symptom Checklist and the Severity Scale and good concurrent
      validity of the FOCI-T Severity Scale. Our results suggested that the FOCI-T was
      found to be a reliable and valid self-report measure to assess obsessive
      compulsive symptoms and severity.

PMID- 25861674
TI  - Evaluation of multiple-scale 3D characterization for coal physical structure with
      DCM method and synchrotron X-ray CT.
AB  - Multiscale nondestructive characterization of coal microscopic physical structure
      can provide important information for coal conversion and coal-bed methane
      extraction. In this study, the physical structure of a coal sample was
      investigated by synchrotron-based multiple-energy X-ray CT at three beam energies
      and two different spatial resolutions. A data-constrained modeling (DCM) approach
      was used to quantitatively characterize the multiscale compositional
      distributions at the two resolutions. The volume fractions of each voxel for four
      different composition groups were obtained at the two resolutions. Between the
      two resolutions, the difference for DCM computed volume fractions of coal matrix
      and pores is less than 0.3%, and the difference for mineral composition groups is
      less than 0.17%. This demonstrates that the DCM approach can account for
      compositions beyond the X-ray CT imaging resolution with adequate accuracy. By
      using DCM, it is possible to characterize a relatively large coal sample at a
      relatively low spatial resolution with minimal loss of the effect due to subpixel
      fine length scale structures. 

PMID- 25861675
TI  - Pollinator behaviour on a food-deceptive orchid Calypso bulbosa and coflowering
      species.
AB  - Food deception as a pollination strategy has inspired many studies over the last
      few decades. Pollinator deception has evolved in many orchids possibly to enhance
      outcrossing. Food-deceptive orchids usually have low pollinator visitation rates
      as compared to rewarding species. They may benefit in visitations from the
      presence (magnet-species hypothesis) or, alternatively, absence of coflowering
      rewarding species (competition hypothesis). We present data on pollinator
      visitations on a deceptive, terrestrial orchid Calypso bulbosa, a species with a
      single flower per plant and whose flowering period partly overlaps with
      rewarding, early flowering willows (Salix sp.) and later-flowering bilberry
      (Vaccinium myrtillus). When surveying inactive bumblebee queens on willows in
      cool weather, about 7% of them carried Calypso pollinia. Most common bumblebee
      species appeared to visit and thus pollinate Calypso. Bumblebees typically
      visited one to three Calypso flowers before flying away, providing some support
      for the outcrossing hypothesis. We conclude that, regarding the pollinations
      strategy, both magnet-species and competition hypotheses have a role in the
      pollination of Calypso, but on different spatial scales. On a large scale
      rewarding species are important for attracting pollinators to a given region, but
      on a small scale absence of competition ensures sufficient pollination rate for
      the deceptive orchid. 

PMID- 25861676
TI  - Stabilities for nonisentropic Euler-Poisson equations.
AB  - We establish the stabilities and blowup results for the nonisentropic Euler
      Poisson equations by the energy method. By analysing the second inertia, we show
      that the classical solutions of the system with attractive forces blow up in
      finite time in some special dimensions when the energy is negative. Moreover, we
      obtain the stabilities results for the system in the cases of attractive and
      repulsive forces. 

PMID- 25861677
TI  - Optimization methods in information and management sciences.

PMID- 25861678
TI  - Effects of nuclear genomes on anther development in cytoplasmic male sterile
      chicories (Cichorium intybus L.): morphological analysis.
AB  - The Cichorium intybus flower development in fertile, cytoplasmic male sterility
      (CMS 524) and various phenotypes carrying the 524 male sterile cytoplasm was
      investigated macroscopically and by light microscopy. The development was similar
      in fertile and in male sterile florets up to meiosis, and then it was affected in
      anther wall structure and pollen grain development in male sterile floret. In the
      male sterile plants, the tapetum intrusion after meiosis was less remarkable, the
      microspores started to abort at vacuolate stage, the connective tissue collapsed,
      and endothecium failed to expand normally and did not undergo cell wall
      lignification, which prevented anther opening since the septum and stomium were
      not disrupted. Crosses undertaken in order to introduce the CMS 524 into two
      different nuclear backgrounds gave rise to morphologically diversified progenies
      due to different nuclear-mitochondrial interactions. Macroscopic and cytological
      investigations showed that pollen-donor plants belonging to Jupiter population
      had potential capacity to restore fertility while the CC line could be considered
      as a sterility maintainer. 

PMID- 25861679
TI  - Thermal behavior of an asphalt pavement in the laboratory and in the parking lot.
AB  - The urban, constructed areas are full of buildings and different kinds of
      pavements and have a noticeable lack of trees and flora. These areas are
      accumulating the heat from the Sun, people, vehicles, and constructions. One
      interesting heat collector is the asphalt pavement. How does the heat transfer to
      different layers under the pavement or does it? What are the temperatures under
      the pavement in Finland where the winter can be pretty hard? How can those
      temperatures be measured accurately? These are the main questions this paper
      gives the preliminary answers to. First the thermal behavior of asphalt and the
      layers beneath are researched in the laboratory and then the measurement field is
      bored and dug in the parking in the Western coast of Finland, 63 degrees 5'45''
      N. Distributed temperature sensing method was found to be a good choice for
      temperature measurements. Thermal behavior of pavement has been monitored in
      different layers and the preliminary results have been published here. The goal
      of this research is to assess the applicability of asphalt pavements for heat
      energy collection. 

PMID- 25861681
TI  - Design time optimization for hardware watermarking protection of HDL designs.
AB  - HDL-level design offers important advantages for the application of watermarking
      to IP cores, but its complexity also requires tools automating these watermarking
      algorithms. A new tool for signature distribution through combinational logic is
      proposed in this work. IPP@HDL, a previously proposed high-level watermarking
      technique, has been employed for evaluating the tool. IPP@HDL relies on spreading
      the bits of a digital signature at the HDL design level using combinational logic
      included within the original system. The development of this new tool for the
      signature distribution has not only extended and eased the applicability of this
      IPP technique, but it has also improved the signature hosting process itself.
      Three algorithms were studied in order to develop this automated tool. The
      selection of a cost function determines the best hosting solutions in terms of
      area and performance penalties on the IP core to protect. An 1D-DWT core and MD5
      and SHA1 digital signatures were used in order to illustrate the benefits of the
      new tool and its optimization related to the extraction logic resources. Among
      the proposed algorithms, the alternative based on simulated annealing reduces the
      additional resources while maintaining an acceptable computation time and also
      saving designer effort and time. 

PMID- 25861680
TI  - Development and evaluation of nanoemulsifying preconcentrate of curcumin for
      colon delivery.
AB  - The present study aimed to develop and optimize a nanoemulsifying preconcentrate
      formulation of curcumin with good emulsification ability and optimal globule
      size, for controlled targeting in colon. Content of formulation variables,
      namely, X1 (Peceol), X2 (Cremophor-EL), and X3 (Transcutol HP), were optimized by
      Box-Behnken design of experiments for its impact on mean globule size (Y1),
      emulsification time (Y2), and time required for drug release (85%) in phosphate
      buffer (pH 7.2), t 85% (Y3). Transmission electron micrographs confirmed that
      there is no coalescence among globules, with size range concordant with the
      globule size analysis by dynamic light scattering technique (100 nm). 3D plots
      indicated that concentration of formulation ingredients significantly influences
      the formulation properties (globule size, emulsification time, and drug release).
      In vitro release profile (in phosphate buffer; pH 7.2) represents the fact that
      more than 50% of the drug was released within initial 15 min whereas in vivo
      release showed limited systemic absorption (C max 200 ng/mL) of curcumin.
      Stability study ensures the protection of drug in alkaline media which may
      further confirm the localised delivery of drug to colonic region. Study
      demonstrated that the nanoemulsifying preconcentrate can be a promising system
      for the colon specific delivery of curcumin to treat local pathologies.

PMID- 25861682
TI  - Evaluation of clinical effectiveness and subjective satisfaction of a new
      toothbrush for postsurgical hygiene care: a randomized split-mouth double-blind
      clinical trial.
AB  - The aim of this RCT was to evaluate plaque control and gingival health promotion
      effectiveness of a new toothbrush with extra-soft filaments in postsurgical sets.
      Ten consecutive patients with at least two scheduled symmetrical periodontal
      surgeries were selected. Following the first periodontal surgery, a test (TB1) or
      control (TB2) toothbrush was randomly assigned. After the second surgery, the
      remaining toothbrush was given. Patients were asked to gently wipe the surgical
      area from days 3 to 7 postoperatively and to gently brush using a roll technique
      from day 7 till the end of the study. Baseline evaluation took place on the day
      of surgery and follow-ups were performed at days 7, 14, and 30 postoperatively. A
      more evident PI reduction was recorded for test toothbrush where a regular
      decrease was observed till day 14; then, this parameter tended to stabilize,
      remaining however lower than that recorded for the control toothbrush. There were
      no statistical differences in the GI between test and control toothbrushes. All
      patients introduced the test toothbrush at surgical site at third day; the
      control toothbrush was introduced within a mean of 9 days. The introduction of
      the test toothbrush 3 days after periodontal surgery may be recommended. 

PMID- 25861683
TI  - Competitive adsorption of metals onto magnetic graphene oxide: comparison with
      other carbonaceous adsorbents.
AB  - Competitive adsorption isotherms of Cu(II), Pb(II), and Cd(II) were examined on a
      magnetic graphene oxide (GO), multiwalled carbon nanotubes (MWCNTs), and powered
      activated carbon (PAC). A series of analyses confirmed the successful synthesis
      of the magnetic GO based on a simple ultrasonification method. Irrespective of
      the adsorbents, the adsorption was highly dependent on pH, and the adsorption was
      well described by the Langmuir isotherm model. The maximum adsorption capacities
      of the adsorbents were generally higher in the order of Pb(II)>Cu(II)>Cd(II),
      which is the same as the degree of the electronegativity and the hydrated radius
      of the metals, suggesting that the metal adsorption may be governed by an ion
      exchange between positively charged metals and negatively charged surfaces, as
      well as diffusion of metals into the surface layer. The adsorption of each metal
      was mostly lower for multi- versus single-metal systems. The antagonistic effects
      were influenced by solution pH as well as the type of metals, and they were
      higher in the order of the magnetic GO>MWCNT>PAC. Dissolved HS played a greater
      role than HS adsorbed onto the adsorbents, competing with the adsorption sites
      for metal complexation.

PMID- 25861684
TI  - Toxicology and disease/cancer therapy in reactive oxygen species-mediated drugs
      and treatments.

PMID- 25861685
TI  - Identification of the bony canal of the posterior superior alveolar nerve and
      artery in the maxillary sinus: tomographic, radiographic, and macroscopic
      analyses.
AB  - The aim of this study was to identify the shape and route of the bony canal of
      the posterior superior alveolar artery (PSAA) and posterior superior alveolar
      nerve (PSAN) using different identification methods, including computed
      tomography (CT), panoramic radiograph, and macroscopic evaluation (corpse and dry
      skull). Twenty-four patients were analyzed by CT and panoramic and posterior
      anterior (PA) radiographs; additionally, 90 dry skulls and 21 dissected
      anatomical specimens were examined. Three-dimensional-CT revealed that the
      lateral wall of the maxillary sinus resembled a tunnel format in 60% of the
      treated patients. Out of all 24 patients, the panoramic radiograph identified the
      bony canal in only one patient; whereas the PA radiograph identified it in 80% of
      the patients. The dry skulls showed tunnellike routes of the PSAA and PSAN in 65%
      of the cases. Moreover, the pathway was also visibly observed in the dissected
      anatomical specimens as a straight shape in 85% of the cases. Thus, our results
      demonstrated that the most common shape of the bony canal of the PSAA and PSAN is
      the tunnel format with a straight route by 3D-CT, posterior anterior radiography,
      and macroscopic evaluation. However, in the panoramic radiographs, it was
      difficult to identify this canal. 

PMID- 25861686
TI  - Moving object detection for video surveillance.
AB  - The emergence of video surveillance is the most promising solution for people
      living independently in their home. Recently several contributions for video
      surveillance have been proposed. However, a robust video surveillance algorithm
      is still a challenging task because of illumination changes, rapid variations in
      target appearance, similar nontarget objects in background, and occlusions. In
      this paper, a novel approach of object detection for video surveillance is
      presented. The proposed algorithm consists of various steps including video
      compression, object detection, and object localization. In video compression, the
      input video frames are compressed with the help of two-dimensional discrete
      cosine transform (2D DCT) to achieve less storage requirements. In object
      detection, key feature points are detected by computing the statistical
      correlation and the matching feature points are classified into foreground and
      background based on the Bayesian rule. Finally, the foreground feature points are
      localized in successive video frames by embedding the maximum likelihood feature
      points over the input video frames. Various frame based surveillance metrics are
      employed to evaluate the proposed approach. Experimental results and comparative
      study clearly depict the effectiveness of the proposed approach. 

PMID- 25861688
TI  - Conceptual framework for the mapping of management process with information
      technology in a business process.
AB  - This study on component framework reveals the importance of management process
      and technology mapping in a business environment. We defined ERP as a software
      tool, which has to provide business solution but not necessarily an integration
      of all the departments. Any business process can be classified as management
      process, operational process and the supportive process. We have gone through
      entire management process and were enable to bring influencing components to be
      mapped with a technology for a business solution. Governance, strategic
      management, and decision making are thoroughly discussed and the need of mapping
      these components with the ERP is clearly explained. Also we suggest that
      implementation of this framework might reduce the ERP failures and especially the
      ERP misfit was completely rectified. 

PMID- 25861687
TI  - Effects of droplet-vitrification cryopreservation based on physiological and
      antioxidant enzyme activities of Brassidium shooting star orchid.
AB  - Protocorm-like bodies (PLBs) of Brassidium Shooting Star orchid were successfully
      cryopreserved using droplet-vitrification method. Vitrification based
      cryopreservation protocol is comprised of preculture, osmoprotection,
      cryoprotection, cooling, rewarming, and growth recovery and each and every step
      contributes to the achievement of successful cryopreservation. In order to reveal
      the lethal and nonlethal damage produced by cryopreservation, histological
      observation, scanning electron microscopy (SEM), and biochemical analysis were
      carried out in both cryopreserved and noncryopreserved PLBs of Brassidium
      Shooting Star orchid comparing with the control PLBs stock culture. Histological
      and scanning electron microscopy analyses displayed structural changes in
      cryopreserved PLBs due to the impact of cryoinjury during exposure to liquid
      nitrogen. Total soluble protein significantly increased throughout the
      dehydration process and the highest value was achieved when PLBs were stored in
      liquid nitrogen. Ascorbate peroxidase (APX) and catalase (CAT) showed the highest
      enzyme activities in both dehydration and cryostorage treatments indicating that
      stress level of PLBs was high during these stages. 

PMID- 25861689
TI  - Challenges of malnutrition care among HIV-infected children on antiretroviral
      treatment in Africa.
AB  - More than 90% of the estimated 3.2 million children with HIV worldwide, at the
      end of 2013, were living in sub-Saharan Africa. The management of these children
      was still difficult in 2014 despite the progress in access to antiretroviral
      drugs. A great number of HIV-infected children are not diagnosed at 6 weeks and
      start antiretroviral treatment late, at an advanced stage of HIV disease
      complicated by other comorbidities such as malnutrition. Malnutrition is a major
      problem in the sub-Saharan Africa global population; it is an additional burden
      for HIV-infected children because they do not respond as well as non-infected
      children to the usual nutritional care. HIV infection and malnutrition interact,
      creating a vicious circle. It is important to understand the relationship between
      these 2 conditions and the effect of antiretroviral treatment on this circle to
      taking them into account for an optimal management of pediatric HIV. An improved
      monitoring of growth during follow-up and the introduction of a nutritional
      support among HIV-infected children, especially at antiretroviral treatment
      initiation, are important factors that could improve response to antiretroviral
      treatment and optimize the management of pediatric HIV in resource-limited
      countries. 

PMID- 25861690
TI  - Protective effects of sodium thiosulfate for cisplatin-mediated ototoxicity in
      patients with head and neck cancer.
AB  - CONCLUSIONS: Intra-arterial high-dose cisplatin chemoradiation (CRT-IA) with
      sodium thiosulfate (STS) causes relatively less severe cisplatin ototoxicity than
      intravenous cisplatin chemoradiation without STS (CRT-IV). The results of this
      study also suggest that early detection of ototoxicity is possible by testing the
      hearing loss at ultra-high frequencies. OBJECTIVES: To investigate protective
      effects of STS against cisplatin ototoxicity. METHODS: Between 2011 and 2013, 18
      patients with head and neck carcinomas were treated with intra-arterial infusions
      of high-dose cisplatin (range 100-180 mg/body, mean 111 mg/body; range 2-5
      courses, mean 3.6 courses) and systemic administration of cisplatin (range 66-185
      mg/body, mean 130 mg/body; range 1-3 courses, mean 2.6 courses) and concurrent
      radiation therapy (range 60-70 Gy, mean 69 Gy). Cisplatin was neutralized by STS
      in CRT-IA but not in CRT-IV. RESULTS: Intra-arterial infusion in the high-dose
      cisplatin group caused significant hearing loss at ultra-high frequencies of 10
      and 12 kHz (p = 0.028, 0.039, respectively), whereas the group receiving systemic
      administration of cisplatin had significant hearing loss at high frequencies of 8
      and 10 kHz (p = 0.016, 0.027, respectively).

PMID- 25861691
TI  - Influence of underpreparation on primary stability of implants inserted in poor
      quality bone sites: an in vitro study.
AB  - PURPOSE: The purpose of this present study was to investigate the relation
      between implant site underpreparation and primary stability in the presence of
      poor-quality bone. MATERIALS AND METHODS: A study was performed on fresh humid
      bovine bone; samples presented no cortical layer with a cancellous structure
      inside and were obtained from the hip. The bones were firmly attached to a base
      device. Sixty sites were prepared according to the protocol provided by the
      manufacturer: a 2-mm pilot drill was introduced to the proper depth and then
      twist drills of 3 and 3.4 mm were used. After site preparation, 20 3.4- * 11-mm
      (standard protocol group), 20 3.8- * 11-mm (10% undersized group), and 20 4.5- *
      11-mm (25% undersized group) implants were inserted at a calibrated maximum
      torque of 70 N-cm at the predetermined speed of 30 rpm. After implant insertion,
      variable torque work (VTW), maximum insertion torque (peak IT), and resonance
      frequency analysis (RFA) values were recorded. RESULTS: The standard protocol
      group showed a mean VTW of 565.77 +/- 219.12 N-cm, a peak IT of 11.3 +/- 4.44 N
      cm, and an RFA of 69.35 +/- 7.35 implant stability quotient (ISQ). The 10%
      undersized group showed a mean VTW of 1,240.24 +/- 407.78 N-cm, a peak IT of
      20.26 +/- 7.03 N-cm, and an RFA of 73.40 +/- 2.33 ISQ. The 25% undersized group
      showed a mean VTW of 1,254.96 +/- 727.49 N-cm, a peak IT of 17.15 +/- 10.39 N-cm,
      and an RFA of 72.30 +/- 6.70 ISQ. For VTW, the difference between the standard
      and undersized protocol values was statistically significant; for peak IT, the
      difference between the standard and 10% undersized protocol values was
      statistically significant; no other statistical differences were found between
      mean values. CONCLUSIONS: In the presence of poor-bone quality, a 10% undersized
      protocol is sufficient to improve the primary stability of the implant;
      additional decreases do not seem to enhance primary stability values.

PMID- 25861692
TI  - Risk Factors for Early and Late Donor-Site Morbidity After Free Fibula Flap
      Harvest.
AB  - PURPOSE: This article reports on the incidence of donor-site complications and
      identifies predictive factors for early and late donor-site complications.
      MATERIALS AND METHODS: From January 2007 through December 2012, 45 patients
      underwent free fibula flap reconstruction and their medical records were
      reviewed. They were asked to complete a questionnaire on the operated leg and
      they were evaluated for ankle stability and ambulatory status. RESULTS: One
      patient (2.2%) developed a complication owing to a hematoma, but no other
      patients had any complications. During the risk factor analysis, no domain was
      found to be statistically associated with early morbidity; late dysfunction was
      noted in 20 patients (57.1%), and of these cases, at least 2 symptoms were found
      in 10 patients (50%). The most common complication was numbness followed by toe
      contracture and abnormal ambulatory movement. During the risk analysis, the
      following domains affected late donor-site morbidity: harvested fibula length,
      operation time, and follow-up time. Furthermore, in cases with complications,
      patients with the osteocutaneous fibula flap complained more than patients with
      the osseous flap (P = .07). CONCLUSION: Early donor-site morbidity was uncommon,
      but late morbidity occurred frequently. Harvested fibula length, operation time,
      and follow-up time were statistically linked to postoperative function.

PMID- 25861693
TI  - Sentinel Lymph Node Biopsy in Oral and Oropharyngeal Squamous Cell Carcinoma:
      Statistical Validation and Impact of Micrometastasis Involvement on the Neck
      Dissection Decision.
AB  - PURPOSE: To evaluate the effectiveness of sentinel lymph node biopsy (SLNB) as an
      optimal staging method in oral and oropharyngeal squamous cell carcinoma (OOSCC)
      and the impact of the extent of SLN involvement on the decision for neck
      dissection (ND). MATERIALS AND METHODS: A prospective cohort study was performed
      in 96 consecutive patients with stage T1 to T4N0M0 OOSCC (mean follow-up, 62.9
      months). SLN localization was determined using cervical lymphoscintigraphy and
      single-photon emission computed tomography. Patients underwent SLNB examination
      and ND. The ND specimen was investigated by hematoxylin and eosin (H&E) staining
      and the SLNs were investigated using H&E staining and step-serial sectioning and
      cytokeratin antibodies AE1 and AE3. The statistical study calculated the
      sensitivity and negative predictive value (NPV). The sample size of 96 patients
      was calculated for a 95% confidence interval with an accuracy of +/-2% and an
      estimated a priori sensitivity of 99% compared with the benchmark. The impact of
      extent of SLN involvement on the decision for ND was analyzed by chi(2) test. A
      logistic regression model was used to assess the association of predictor
      variables with SLN involvement and neck disease. RESULTS: The diagnostic
      accuracy, sensitivity, NPV, and negative likelihood ratio were 95%, 88%, 94%, and
      0.06. The statistical comparison between the extent of metastatic involvement of
      the SLN and neck disease was important for SLN macrometastasis (odds ratio =
      11.9), but not for SLN micrometastasis (odds ratio = 0.93). CONCLUSIONS: SLNB
      examination is an excellent staging method in OOSCC. The present data indicate a
      very small risk of additional lymph node metastasis with SLN micrometastasis.

PMID- 25861694
TI  - Endoscopic-Assisted Resection of Benign Tumors of the Accessory Parotid Gland.
AB  - PURPOSE: Modified endoscopically assisted resection of benign tumors in the
      accessory parotid gland region (APGR) has been reported, and the surgery confers
      a potential risk of injury to the great auricular nerve. This clinical research
      study provides an updated approach for the resection of benign tumors of the
      APGR. PATIENTS AND METHODS: Thirteen cases diagnosed with primary benign tumors
      in the APGR were treated by endoscopically assisted resection through a margin of
      the tragus, and its feasibility was evaluated. RESULTS: All tumors were
      completely resected. The procedures lasted 45 to 70 minutes (mean, 54 minutes).
      None of the endoscopically assisted surgeries proceeded to open surgery. The
      patients were followed for 3 to 14 months, without postoperative complications,
      including pain, facial or auricular nerve weakness, salivary fistula, infection,
      tumor recurrence, Frey syndrome, or depression deformity. The scars were
      concealed and esthetically satisfactory. CONCLUSION: Endoscopically assisted
      resection of benign tumors through a margin of the tragus in the APGR is a safe
      technique that achieves excellent esthetic and functional results.

PMID- 25861695
TI  - Joop van der Pligt: 22 November 1951-9 January, 2015.

PMID- 25861697
TI  - Association of Long-Term Nicotine Abstinence With Normal Metabotropic Glutamate
      Receptor-5 Binding.
AB  - BACKGROUND: Nicotine addiction is a major public health problem and is associated
      with primary glutamatergic dysfunction. We recently showed marked global
      reductions in metabotropic glutamate receptor type 5 (mGluR5) binding in smokers
      and recent ex-smokers (average abstinence duration of 25 weeks). The goal of this
      study was to examine the role of mGluR5 downregulation in nicotine addiction by
      investigating a group of long-term ex-smokers (abstinence >1.5 years), and to
      explore associations between mGluR5 binding and relapse in recent ex-smokers.
      METHODS: Images of mGluR5 receptor binding were acquired in 14 long-term ex
      smokers, using positron emission tomography with radiolabeled [11C]ABP688, which
      binds to an allosteric site with high specificity. RESULTS: Long-term ex-smokers
      and individuals who had never smoked showed no differences in mGluR5 binding in
      any of the brain regions examined. Long-term ex-smokers showed significantly
      higher mGluR5 binding than recent ex-smokers, most prominently in the frontal
      cortex (42%) and thalamus (57%). CONCLUSIONS: Our findings suggest that
      downregulation of mGluR5 is a pathogenetic mechanism underlying nicotine
      dependence and the high relapse rate in individuals previously exposed to
      nicotine. Therefore, mGluR5 receptor binding appears to be an effective biomarker
      in smoking and a promising target for the discovery of novel medication for
      nicotine dependence and other substance-related disorders.

PMID- 25861696
TI  - Gq-DREADD Selectively Initiates Glial Glutamate Release and Inhibits Cue-induced
      Cocaine Seeking.
AB  - BACKGROUND: Glial cells of the central nervous system directly influence neuronal
      activity by releasing neuroactive small molecules, including glutamate. Long
      lasting cocaine-induced reductions in extracellular glutamate in the nucleus
      accumbens core (NAcore) affect synaptic plasticity responsible for relapse
      vulnerability. METHODS: We transduced NAcore astrocytes with an adeno-associated
      virus vector expressing hM3D designer receptor exclusively activated by a
      designer drug (DREADD) under control of the glial fibrillary acidic protein
      promoter in 62 male Sprague Dawley rats, 4 dominant-negative soluble N
      ethylmaleimide-sensitive factor attachment protein receptor mice, and 4 wild-type
      littermates. Using glutamate biosensors, we measured NAcore glutamate levels
      following intracranial or systemic administration of clozapine N-oxide (CNO) and
      tested the ability of systemic CNO to inhibit reinstated cocaine or sucrose
      seeking following self-administration and extinction training. RESULTS:
      Administration of CNO in glial fibrillary acidic protein-hM3D-DREADD transfected
      animals increased NAcore extracellular glutamate levels in vivo. The glial origin
      of released glutamate was validated by an absence of CNO-mediated release in mice
      expressing a dominant-negative soluble N-ethylmaleimide-sensitive factor
      attachment protein receptor variant in glia. Also, CNO-mediated release was
      relatively insensitive to N-type calcium channel blockade. Systemic
      administration of CNO inhibited cue-induced reinstatement of cocaine seeking in
      rats extinguished from cocaine but not sucrose self-administration. The capacity
      to inhibit reinstated cocaine seeking was prevented by systemic administration of
      the group II metabotropic glutamate receptor antagonist LY341495. CONCLUSIONS:
      DREADD-mediated glutamate gliotransmission inhibited cue-induced reinstatement of
      cocaine seeking by stimulating release-regulating group II metabotropic glutamate
      receptor autoreceptors to inhibit cue-induced synaptic glutamate spillover.

PMID- 25861698
TI  - Phenotypic Association Analyses With Copy Number Variation in Recurrent
      Depressive Disorder.
AB  - BACKGROUND: Defining the molecular genomic basis of the likelihood of developing
      depressive disorder is a considerable challenge. We previously associated rare,
      exonic deletion copy number variants (CNV) with recurrent depressive disorder
      (RDD). Sex chromosome abnormalities also have been observed to co-occur with RDD.
      METHODS: In this reanalysis of our RDD dataset (N = 3106 cases; 459 screened
      control samples and 2699 population control samples), we further investigated the
      role of larger CNVs and chromosomal abnormalities in RDD and performed
      association analyses with clinical data derived from this dataset. RESULTS: We
      found an enrichment of Turner's syndrome among cases of depression compared with
      the frequency observed in a large population sample (N = 34,910) of live-born
      infants collected in Denmark (two-sided p = .023, odds ratio = 7.76 [95%
      confidence interval = 1.79-33.6]), a case of diploid/triploid mosaicism, and
      several cases of uniparental isodisomy. In contrast to our previous analysis,
      large deletion CNVs were no more frequent in cases than control samples, although
      deletion CNVs in cases contained more genes than control samples (two-sided p =
      .0002). CONCLUSIONS: After statistical correction for multiple comparisons, our
      data do not support a substantial role for CNVs in RDD, although (as has been
      observed in similar samples) occasional cases may harbor large variants with
      etiological significance. Genetic pleiotropy and sample heterogeneity suggest
      that very large sample sizes are required to study conclusively the role of
      genetic variation in mood disorders.

PMID- 25861699
TI  - Effect of the Novel Positive Allosteric Modulator of Metabotropic Glutamate
      Receptor 2 AZD8529 on Incubation of Methamphetamine Craving After Prolonged
      Voluntary Abstinence in a Rat Model.
AB  - BACKGROUND: Cue-induced methamphetamine craving increases after prolonged forced
      (experimenter-imposed) abstinence from the drug (incubation of methamphetamine
      craving). Here, we determined whether this incubation phenomenon would occur
      under conditions that promote voluntary (self-imposed) abstinence. We also
      determined the effect of the novel metabotropic glutamate receptor 2 positive
      allosteric modulator, AZD8529, on incubation of methamphetamine craving after
      forced or voluntary abstinence. METHODS: We trained rats to self-administer
      palatable food (6 sessions) and then to self-administer methamphetamine under two
      conditions: 12 sessions (9 hours/day) or 50 sessions (3 hours/day). We then
      assessed cue-induced methamphetamine seeking in extinction tests after 1 or 21
      abstinence days. Between tests, the rats underwent either forced abstinence (no
      access to the food- or drug-paired levers) or voluntary abstinence (achieved via
      a discrete choice procedure between methamphetamine and palatable food; 20 trials
      per day) for 19 days. We also determined the effect of subcutaneous injections of
      AZD8529 (20 and 40 mg/kg) on cue-induced methamphetamine seeking 1 day or 21 days
      after forced or voluntary abstinence. RESULTS: Under both training and abstinence
      conditions, cue-induced methamphetamine seeking in the extinction tests was
      higher after 21 abstinence days than after 1 day (incubation of methamphetamine
      craving). AZD8529 decreased cue-induced methamphetamine seeking on day 21 but not
      day 1 of forced or voluntary abstinence. CONCLUSIONS: We introduce a novel animal
      model to study incubation of drug craving and cue-induced drug seeking after
      prolonged voluntary abstinence, mimicking the human condition of relapse after
      successful contingency management treatment. Our data suggest that positive
      allosteric modulators of metabotropic glutamate receptor 2 should be considered
      for relapse prevention.

PMID- 25861700
TI  - Depressive Rumination, the Default-Mode Network, and the Dark Matter of Clinical
      Neuroscience.
AB  - The intuitive association between self-focused rumination in major depressive
      disorder (MDD) and the self-referential operations performed by the brain's
      default-mode network (DMN) has prompted interest in examining the role of the DMN
      in MDD. In this article, we present meta-analytic findings showing reliably
      increased functional connectivity between the DMN and subgenual prefrontal cortex
      (sgPFC)-connectivity that often predicts levels of depressive rumination. We also
      present meta-analytic findings that, while there is reliably increased regional
      cerebral blood flow in sgPFC in MDD, no such abnormality has been reliably
      observed in nodes of the DMN. We then detail a model that integrates the body of
      research presented. In this model, we propose that increased functional
      connectivity between sgPFC and the DMN in MDD represents an integration of the
      self-referential processes supported by the DMN with the affectively laden,
      behavioral withdrawal processes associated with sgPFC-an integration that
      produces a functional neural ensemble well suited for depressive rumination and
      that, in MDD, abnormally taxes only sgPFC and not the DMN. This synthesis
      explains a broad array of existing data concerning the neural substrates of
      depressive rumination and provides an explicit account of functional
      abnormalities in sgPFC in MDD. 

PMID- 25861701
TI  - The Human Model: Changing Focus on Autism Research.
AB  - The lack of live human brain cells for research has slowed progress toward
      understanding the mechanisms underlying autism spectrum disorders. A human model
      using reprogrammed patient somatic cells offers an attractive alternative, as it
      captures a patient's genome in relevant cell types. Despite the current
      limitations, the disease-in-a-dish approach allows for progressive time course
      analyses of target cells, offering a unique opportunity to investigate the
      cellular and molecular alterations before symptomatic onset. Understanding the
      current drawbacks of this model is essential for the correct data interpretation
      and extrapolation of conclusions applicable to the human brain. Innovative
      strategies for collecting biological material and clinical information from large
      patient cohorts are important for increasing the statistical power that will
      allow for the extraction of information from the noise resulting from the
      variability introduced by reprogramming and differentiation methods. Working with
      large patient cohorts is also important for understanding how brain cells derived
      from diverse human genetic backgrounds respond to specific drugs, creating the
      possibility of personalized medicine for autism spectrum disorders. 

PMID- 25861703
TI  - Paradoxical Expectation: Oscillatory Brain Activity Reveals Social Interaction
      Impairment in Schizophrenia.
AB  - BACKGROUND: People with schizophrenia show social impairments that are related to
      functional outcomes. We tested the hypothesis that social interaction impairments
      in people with schizophrenia are related to alterations in the predictions of
      others' behavior and explored their underlying neurobiological mechanisms.
      METHODS: Electroencephalography was performed in 20 patients with schizophrenia
      and 25 well-matched control subjects. Participants played as proposers in the
      repeated version of the Ultimatum Game believing that they were playing with
      another human or with a computer. The power of oscillatory brain activity was
      obtained by means of the wavelet transform. We performed a trial-by-trial
      correlation between the oscillatory activity and the risk of the offer. RESULTS:
      Control subjects adapted their offers when playing with computers and tended to
      maintain their offers when playing with humans, as such revealing learning and
      bargaining strategies, respectively. People with schizophrenia presented the
      opposite pattern of behavior in both games. During the anticipation of others'
      responses, the power of alpha oscillations correlated with the risk of the offers
      made, in a different way in both games. Patients with schizophrenia presented a
      greater correlation in computer games than in human games; control subjects
      showed the opposite pattern. The alpha activity correlated with positive
      symptoms. CONCLUSIONS: Our results reveal an alteration in social interaction in
      patients with schizophrenia that is related to oscillatory brain activity,
      suggesting maladjustment of expectation when patients face social and nonsocial
      agents. This alteration is related to psychotic symptoms and could guide further
      therapies for improving social functioning in patients with schizophrenia.

PMID- 25861704
TI  - Lack of meta-analytic evidence for an impact of COMT Val158Met genotype on brain
      activation during working memory tasks.

PMID- 25861702
TI  - Protein Kinase C Epsilon Activity in the Nucleus Accumbens and Central Nucleus of
      the Amygdala Mediates Binge Alcohol Consumption.
AB  - BACKGROUND: Protein kinase C epsilon (PKCepsilon) is emerging as a potential
      target for the development of pharmacotherapies to treat alcohol use disorders,
      yet little is known regarding how a history of a highly prevalent form of
      drinking, binge alcohol intake, influences enzyme priming or the functional
      relevance of kinase activity for excessive alcohol intake. METHODS:
      Immunoblotting was employed on tissue from subregions of the nucleus accumbens
      (NAc) and the amygdala to examine both idiopathic and binge drinking-induced
      changes in constitutive PKCepsilon priming. The functional relevance of
      PKCepsilon translocation for binge drinking and determination of potential
      upstream signaling pathways involved were investigated using neuropharmacologic
      approaches within the context of two distinct binge drinking procedures, drinking
      in the dark and scheduled high alcohol consumption. RESULTS: Binge alcohol
      drinking elevated p(Ser729)-PKCepsilon levels in both the NAc and the central
      nucleus of the amygdala (CeA). Moreover, immunoblotting studies of selectively
      bred and transgenic mouse lines revealed a positive correlation between the
      propensity to binge drink alcohol and constitutive p(Ser729)-PKCepsilon levels in
      the NAc and CeA. Finally, neuropharmacologic inhibition of PKCepsilon
      translocation within both regions reduced binge alcohol consumption in a manner
      requiring intact group 1 metabotropic glutamate receptors, Homer2, phospholipase
      C, and/or phosphotidylinositide-3 kinase function. CONCLUSIONS: Taken together,
      these data indicate that PKCepsilon signaling in both the NAc and CeA is a major
      contributor to binge alcohol drinking and to the genetic propensity to consume
      excessive amounts of alcohol.

PMID- 25861705
TI  - B-cell-associated immune profiles in patients with decompensated cirrhosis.
AB  - OBJECTIVE: Previous observations on immune dysfunction in decompensated cirrhosis
      have raised the possibility of B-cell impairment. METHODS: B-cell subsets in
      decompensated cirrhotic patients were investigated. Twenty-six decompensated
      cirrhotic patients and 26 healthy controls were included in this study. The
      percentages of B-cell subsets, such as mature, memory, immature B cells, and
      interleukin (IL)-10+-B-cell subpopulations, were measured using fluorescent
      activated cell sorting. B-cell-associated cytokines (IL-10, IL-21 and IL-4) were
      determined using an enzyme-linked immunosorbent assay. RESULTS: The percentage of
      total B cells and mature B cells increased in patients with decompensated
      cirrhosis compared to healthy controls. The proportions of memory B cells were
      significantly lower in the decompensated cirrhosis group than the control group.
      However, the frequency of immature B cells and the percentage of IL-10-expressing
      cells that were CD19+, memory, mature, or immature B cells were not significantly
      different between the two groups. Serum levels of IL-10, IL-21, and IL-4 were
      significantly lower in the decompensated cirrhosis group compared to the control
      group. CONCLUSION: These results indicate significant alterations in peripheral
      blood B-cell subsets in patients with decompensated cirrhosis. Specifically, a
      profound reduction of memory B cells was observed in spite of an increase in
      total B-cell populations in decompensated cirrhotic patients. This implies the
      underlying mechanisms of impaired immune response in these patients.

PMID- 25861706
TI  - Interactive effects of GPI stimulation and levodopa on postural control in
      Parkinson's disease.
AB  - INTRODUCTION: Postural instability is a major source of disability in idiopathic
      Parkinson's disease (IPD). Deep brain stimulation of the globus pallidus internus
      (GPI-DBS) improves clinician-rated balance control but there have been few
      quantitative studies of its interactive effects with levodopa (L-DOPA). The
      purpose of this study was to compare the short-term and interactive effects of
      GPI-DBS and L-DOPA on objective measures of postural stability in patients with
      longstanding IPD. METHODS: Static and dynamic posturography during a whole-body
      leaning task were performed in 10 IPD patients with bilateral GPI stimulators
      under the following conditions: untreated (OFF); L-DOPA alone; DBS alone; DBS+L
      DOPA, and in 9 healthy Control subjects. Clinical status was assessed using the
      UPDRS and AIMS Dyskinesia Scale. RESULTS: Static sway was greater in IPD patients
      in the OFF state compared to the Control subjects and was further increased by L
      DOPA and reduced by GPI-DBS. In the dynamic task, L-DOPA had a greater effect
      than GPI-DBS on improving Start Time, but reduced the spatial accuracy and
      directional control of the task. When the two therapies were combined, GPI-DBS
      prevented the L-DOPA induced increase in static sway and improved the accuracy of
      the dynamic task. CONCLUSION: The findings demonstrate GPI-DBS and L-DOPA have
      differential effects on temporal and spatial aspects of postural control in IPD
      and that GPI-DBS counteracts some of the adverse effects of L-DOPA. Further
      studies on larger numbers of patients with GPI stimulators are required to
      confirm these findings and to clarify the contribution of dyskinesias to impaired
      dynamic postural control.

PMID- 25861707
TI  - B-vitamin status in relation to bone mineral density in treated celiac disease
      patients.
AB  - OBJECTIVES: Patients with celiac disease (CD) are at increased risk of
      osteoporosis and compromised B-vitamin status. Emerging evidence supports a
      beneficial role of folate and the metabolically related B-vitamins in bone health
      in generally healthy adults, but no previous study has investigated this in CD
      patients. The aim of the current study was to examine the relationship of folate,
      vitamins B12, B6 and B2 (riboflavin), and the related metabolite homocysteine,
      with bone mineral density (BMD) in CD patients. MATERIALS AND METHODS: Of the 400
      treated adult CD patients invited to participate, 110 responded and met the
      eligibility criteria for study participation. BMD was measured using dual energy
      X-ray absorptiometry scanning at the lumbar spine (L1-L4), femoral neck, and
      total hip sites. Biomarker status of the relevant B-vitamins and homocysteine,
      and dietary B-vitamin intakes, were measured. RESULTS: The significant predictors
      of low BMD were increasing age (B = 0.080, p < 0.001) and decreasing weight (B =
      0.072, p = 0.004), whereas no significant relationship with serum 25
      hydroxyvitamin D (B = 0.093, p = 0.928) was observed. Following adjustment for
      these predictors, serum vitamin B12 (but no other B-vitamin biomarker) was found
      to be a significant determinant of BMD at the femoral neck (beta = 0.416, p =
      0.011) and total hip (beta = 0.327, p = 0.049) in men only. No significant
      relationships were found between any of the B-vitamin biomarkers investigated and
      BMD (at any measured site) in women. CONCLUSION: These findings add to current
      evidence suggesting a potential role of vitamin B12 in BMD, particularly in men,
      and show such a relationship for the first time in CD patients.

PMID- 25861709
TI  - The UWIMONA Pediatric Epileptic Seizure Screening Questionnaire was equivalent to
      clinical assessment in identifying children with epilepsy.
AB  - OBJECTIVES: To assess the validity and reliability of a screening questionnaire
      administered to parents/caregivers to detect behaviors suggestive of epileptic
      seizures in children. STUDY DESIGN AND SETTING: We developed a 10-item
      questionnaire, which was administered to 120 parents/caregivers of children
      attending hospital-based clinics/pediatric neurologists' offices. Receiver
      operating characteristic (ROC) curve analysis was used to assess the discriminant
      ability of the questionnaire and determine cutoff points. Questionnaire
      sensitivity and specificity were compared with clinical assessment by a
      pediatrician and pediatric neurologist. The questionnaire was readministered to
      25 parents/caregivers after 1 month to assess reliability. RESULTS: The 120
      children had the following characteristics: 58% with epilepsy, 55% male, mean
      (standard deviation) age 8.1 (3.2) years. A positive response to >=1 item had the
      highest sensitivity (89%) and specificity (91%), with a ROC area under curve of
      0.91 (95% confidence interval: 0.86, 0.97). The validity of the questionnaire was
      similar to the clinical evaluation by the pediatric neurologist and pediatrician.
      The Spearman correlation coefficient for the total score from repeat
      administration of the questionnaire was 0.95 (P < 0.01). CONCLUSION: The UWIMONA
      Pediatric Epileptic Seizure Screening Questionnaire is a valid and reliable
      screening instrument and performed similarly when compared with evaluation by an
      experienced clinician.

PMID- 25861708
TI  - Functional Chimeras of GLIC Obtained by Adding the Intracellular Domain of Anion-
      and Cation-Conducting Cys-Loop Receptors.
AB  - Pentameric ligand-gated ion channels (pLGICs), also called Cys-loop receptors in
      eukaryotic superfamily members, play diverse roles in neurotransmission and serve
      as primary targets for many therapeutic drugs. Structural studies of full-length
      eukaryotic pLGICs have been challenging because of glycosylation, large size,
      pentameric assembly, and hydrophobicity. X-ray structures of prokaryotic pLGICs,
      including the Gloeobacter violaceus LGIC (GLIC) and the Erwinia chrysanthemi LGIC
      (ELIC), and truncated eukaryotic pLGICs have significantly improved and
      complemented the understanding of structural details previously obtained with
      acetylcholine-binding protein and Torpedo nicotinic acetylcholine receptors.
      Prokaryotic pLGICs share their overall structural features with eukaryotic pLGICs
      for the ligand-binding extracellular and channel-lining transmembrane domains.
      The large intracellular domain (ICD) is present only in eukaryotic members and is
      characterized by a low level of sequence conservation and significant variability
      in length (50-250 amino acids), making the ICD a potential target for the
      modulation of specific pLGIC subunits. None of the structures includes a complete
      ICD. Here, we created chimeras by adding the ICD of cation-conducting (nAChR
      alpha7) and anion-conducting (GABArho1, Glyalpha1) eukaryotic homopentamer
      forming pLGICs to GLIC. GLIC-ICD chimeras assemble into pentamers to form proton
      gated channels, as does the parent GLIC. Additionally, the sensitivity of the
      chimeras toward modulation of functional maturation by chaperone protein RIC-3 is
      preserved as in those of the parent eukaryotic channels. For a previously
      described GLIC-5HT3A-ICD chimera, we now provide evidence of its successful large
      scale expression and purification to homogeneity. Overall, the chimeras provide
      valuable tools for functional and structural studies of eukaryotic pLGIC ICDs. 

PMID- 25861710
TI  - Estimating municipal solid waste generation by different activities and various
      resident groups in five provinces of China.
AB  - The quantities and composition of municipal solid waste (MSW) are important
      factors in the planning and management of MSW. Daily human activities were
      classified into three groups: maintenance activities (meeting the basic needs of
      food, housing and personal care, MA); subsistence activities (providing the
      financial support requirements, SA); and leisure activities (social and
      recreational pursuits, LA). A model, based on the interrelationships of
      expenditure on consumer goods, time distribution, daily activities, residents
      groups, and waste generation, was employed to estimate MSW generation by
      different activities and resident groups in five provinces (Zhejiang, Guangdong,
      Hebei, Henan and Sichuan) of China. These five provinces were chosen for this
      study and the distribution patterns of MSW generated by different activities and
      resident groups were revealed. The results show that waste generation in SA and
      LA fluctuated slightly from 2003 to 2008. For general waste generation in the
      five provinces, MA accounts for more than 70% of total MSW, SA approximately 10%,
      and LA between 10% and 16% by urban residents in 2008. Females produced more
      daily MSW than males in MA. Males produced more daily MSW than females in SA and
      LA. The wastes produced at weekends in MA and LA were far greater than on
      weekdays, but less than on weekdays for SA wastes. Furthermore, one of the model
      parameters (the waste generation per unit of consumer expenditure) is inversely
      proportional to per-capita disposable income of urban residents. A significant
      correlation between gross domestic product (GDP) and waste generation by SA was
      observed with a high coefficient of determination. 

PMID- 25861711
TI  - Anterior Shoulder Instability Is Associated With an Underlying Deficiency of the
      Bony Glenoid Concavity.
AB  - PURPOSE: To determine whether anterior shoulder instability is associated with an
      inherent deficiency of the bony glenoid concavity, which results in a reduced
      bony shoulder stability ratio (BSSR). METHODS: In this case-control study, we
      searched the institutional database for patients treated for unilateral recurrent
      anterior shoulder instability. We included 30 consecutive patients with
      atraumatic instability, 30 consecutive patients with traumatic instability, and
      36 matched healthy controls, for a total of 96 shoulders. Computed tomography
      images of the unaffected shoulders of the instability patients were compared with
      images of the ipsilateral shoulders of age- and sex-matched healthy controls for
      differences in glenoid morphology. By use of a mathematical formula based on
      Pythagorean trigonometric identities, the mean BSSRs of the different groups were
      calculated and compared. Validation of the formula was accomplished by finite
      element analysis. RESULTS: The mean BSSR of atraumatic instability patients was
      17.9% +/- 8.5% and therefore significantly lower than the mean BSSR of 31.1% +/-
      7.5% of the control group (13.2%; 95% confidence interval [CI], 9.1% to 17.4%; P
      < .001). The mean BSSR of the traumatic instability group was higher, at 23.9% +/
      8.5% (P = .007), but still showed a deficit of 7.2% (95% CI, 2.8% to 11.7%; P =
      .002) compared with controls. The atraumatic instability group showed a mean
      reduction of 0.9 mm (95% CI, 0.6 to 1.1 mm; P < .001) in concavity depth and a
      decrease of 2.9 degrees  (95% CI, 0.4 degrees  to 5.3 degrees ; P = .021) in
      concavity retroversion, whereas the traumatic instability patients had a
      reduction of 0.4 mm (95% CI, 0.1 to 0.8 mm; P = .006) in concavity depth. Neither
      of the instability groups differed significantly from their respective controls
      in terms of glenoid concavity diameter, head radius, or glenoid vault morphology.
      CONCLUSIONS: Anterior shoulder instability is associated with an inherent
      flattening of the bony glenoid concavity, which significantly decreases the BSSR.
      The deficiency appears to be more pronounced in patients with atraumatic
      instability than in patients with traumatic instability. LEVEL OF EVIDENCE: Level
      III, case-control study.

PMID- 25861712
TI  - Open-Wedge High Tibial Osteotomy and Combined Abrasion/Microfracture in Severe
      Medial Osteoarthritis and Varus Malalignment: 5-Year Results and Arthroscopic
      Findings After 2 Years.
AB  - PURPOSE: To determine survivorship and functional results of medial open-wedge
      high tibial osteotomy (HTO) combined with a chondral resurfacing procedure
      (abrasion/microfracture) in patients with Kellgren-Lawrence grade 3 and 4
      osteoarthritis with full-thickness cartilage defects and varus malalignment.
      METHODS: From September 2005 to December 2008, all cases of HTO (fixation with an
      angular-stable internal fixator) combined with a chondral resurfacing procedure
      performed at our institution were prospectively surveyed, with a minimum follow
      up of 5 years, regarding survival (not requiring arthroplasty), functional
      outcome (subjective International Knee Documentation Committee [IKDC] score), and
      subjective satisfaction (whether patients would undergo the operation again).
      Clinical evaluation (according to objective IKDC parameters), radiologic
      evaluation, and revision arthroscopy for evaluation of regenerated cartilage were
      performed between 1 and 2 years. RESULTS: A total of 91 knees (85 patients; mean
      age, 50.4 +/- 8.0 years; age range, 28.3 to 67.7 years) were included. The
      survival rate was 95.2% (95% confidence interval, 90.7% to 99.7%) at 5 years,
      with 4 conversions to arthroplasty (3 unicondylar and 1 total knee arthroplasty;
      follow-up rate, 87.9%). Subjective IKDC scores significantly improved from 45.1
      +/- 11.6 points preoperatively to 69.1 +/- 14.2 points after 1 year, 66.4 +/-
      14.5 points after 3 years, and 67.2 +/- 14.4 points after 5 years (P < .001). In
      94.9% of the cases patients were satisfied with the result after 5 years,
      including those with arthroplasty. Revision arthroscopy was performed in 80 cases
      (87.9%) at 1.5 +/- 0.8 years: Cartilage regeneration was graded good in 50.0% and
      excellent in 25.8% on the tibial side compared with 48.1% and 39.0%,
      respectively, on the femoral side (P < .001). The overall complication rate was
      6.6%. CONCLUSIONS: HTO in combination with a chondral resurfacing procedure is
      effective in the treatment of severe medial osteoarthritis and varus
      malalignment. The effect of the chondral resurfacing in this combined approach
      remains unclear. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

PMID- 25861713
TI  - [Ulcerative colitis associated with autoimmune pancreatitis, sialadenitis and
      leukocytoclastic vasculitis].

PMID- 25861714
TI  - New aspects on the pathogenesis of renal disorders related to monoclonal
      gammopathies.
AB  - BACKGROUND: Multiple myeloma and other related monoclonal gammopathies are
      frequently encountered conditions associated with renal damage, especially in
      elderly population. They are arising from clonal proliferation of plasma cells in
      bone marrow producing various quantities of abnormal monoclonal immunoglobulins,
      or their components/fragments. SUMMARY: These abnormal proteins differ from
      normal immunoglobulins in the amino acid sequence and in the three-dimensional
      structure of the molecule, which may determine their toxicity. Kidney seems to be
      a target organ as a major catabolic site. The pathology of renal disease is
      highly heterogeneous involving a variety of different mechanisms, which are
      divided into immunoglobulin dependent and immunoglobulin independent mechanisms.
      The Ig-dependent mechanisms may involve the four components of the kidney
      parenchyma, and the primary structure of these proteins determine the pattern of
      renal disease. KEY MESSAGE: This review summarizes the existing literature in the
      pathobiology of multiple myeloma, and the pathological properties of the M
      proteins, focusing on the mechanisms of the renal manifestations related to these
      abnormal proteins, especially glomerular injury. Also it supports the opinion
      that monoclonal gammopathy of undetermined significance (MGUS) should not be used
      in cases where there is proven renal impairment due to these proteins, even if it
      is mild and does not meet the current criteria.

PMID- 25861715
TI  - [Drug pharmacokinetics in renal failure: What's new?].
AB  - The prevalence and incidence of chronic kidney disease (CKD) has steadily
      increased over the past two decades attributed to an important raise of cases of
      diabetes, hypertension and obesity, leading risk factors of renal failure. CKD is
      known to impair drug disposition of non-renally eliminated medications that may
      lead to unintended toxicity or lower therapeutic effect despite dose adjustment
      according to glomerular filtration rate (GFR). Modulation of metabolism enzymes
      (cytochrome P450, phase II) and drug transporters in various organs (intestines,
      liver, kidneys and brain) are being held responsible for altered pharmacokinetics
      where uremic toxins, inflammatory cytokines and parathyroid hormone, common
      factors present in CKD, may be considered possible culprits. This review gives a
      thorough summary of the recent preclinical, clinical studies and Food and Drug
      Administration (FDA) guidelines and allows a current understanding of drug
      absorption, distribution, metabolism and excretion in CKD. 

PMID- 25861716
TI  - Comparison of Adjuvant Radiation Therapy Alone Versus Radiation Therapy and
      Endocrine Therapy in Elderly Women With Early-Stage, Hormone Receptor-Positive
      Breast Cancer Treated With Breast-Conserving Surgery.
AB  - BACKGROUND: Randomized data examining adjuvant radiation therapy (RT) alone in
      elderly women with low-risk, hormone receptor-positive (HR(+)) breast cancer is
      lacking. We investigated the outcomes for elderly women treated with adjuvant RT
      alone versus RT plus endocrine therapy (ET) after breast-conserving surgery.
      PATIENTS AND METHODS: We queried our institutional breast cancer database for the
      following patients: age > 65 years, stage T1-T2N0, HR(+), and treatment with
      breast-conserving surgery, including adjuvant RT. The chi(2) analysis identified
      significant baseline differences between the groups. Cox proportional hazard
      methods identified predictors of endpoints on multivariate analysis. Kaplan-Meier
      estimates of survival were compared using the log-rank test. RESULTS: A total of
      504 patients were identified, 311 had undergone RT plus ET (62%) and 193, RT
      alone (38%). The median follow-up time was 88 months. The RT-alone group versus
      RT plus ET group had different median age (72 vs.71 years, P < .001), different
      median tumor size (1 vs. 1.3 cm, P < .001), lower grade (40% vs. 29%, P = .05),
      and fewer close or positive margins (11% vs. 19%, P = .01). The adherence rate to
      prescribed ET was 70%. Tumor size predicted an increased risk of distant
      metastasis (DM) (hazard ratio, 1.96; 95% confidence interval [CI], 1.23-3.13) and
      worse disease-free survival (DFS) (hazard ratio, 1.86; 95% CI, 1.22-2.86). ET
      nonadherence versus adherence predicted for risk of DM (hazard ratio, 5.03; 95%
      CI, 1.98-12.66) and DFS (HR, 4.24; 95% CI, 1.9-10.3). Of the women with DM, 83.8%
      had tumors > 1 cm in size. CONCLUSION: ET nonadherence and tumor size > 1 cm
      predicted an increased risk of DM and worse DFS, favoring the addition of ET in
      this group. However, RT alone for women with tumors less than or equal to 1 cm
      may be appropriate.

PMID- 25861717
TI  - Chinese herbal medicine as adjuvant treatment to chemotherapy for multidrug
      resistant tuberculosis (MDR-TB): A systematic review of randomised clinical
      trials.
AB  - INTRODUCTION: Chinese herbal medicine (CHM) has been increasingly used as an
      adjuvant treatment for multi-drug resistant tuberculosis (MDR-TB) in China. To
      inform clinical practice, we performed a systematic review on the beneficial
      effect and safety of CHM for MDR-TB. METHODS: We searched six electronic
      databases for randomised clinical trials (RCTs) of CHM for MDR-TB. We used RevMan
      5.2 software for data analyses with effect estimates as risk ratio (RR) with 95%
      confidence interval (CI). RESULTS: 30 RCTs involving 3374 participants with MDR
      TB were included. The methodological quality was generally poor in terms of risk
      of bias. Meta-analyses favoured CHM plus chemotherapy on sputum bacteriological
      conversion rate compared with chemotherapy alone after initiation of treatment
      (6th mos: RR 1.27, 95% CI 1.14 to 1.41, n = 12; 12th mos: RR 1.30, 95% CI 1.11 to
      1.52, n = 6; 18th mos: RR 1.19, 95% CI 1.11 to 1.27, n = 9). Compared with
      chemotherapy alone, meta-analyses showed benefit from CHM plus chemotherapy on
      lung lesions resorption rate (6th mos: RR 1.10, 95% CI 0.91 to 1.32, n = 5; 12th
      mos: RR 1.26, 95% CI 1.10 to 1.45, n = 4; 18th mos: RR 1.19, 95% CI 1.08 to 1.32,
      n = 7) and cavity closure rate (12th mos: RR 1.48, 95% CI 1.06 to 2.07, n = 2;
      18th mos: RR 1.26, 95% CI 1.04 to 1.53, n = 5), relapse rate (RR 0.28, 95% CI
      0.16 to 0.50, n = 4), and abnormal liver function (RR 0.56, 95% CI 0.46 to 0.69,
      n = 14). No serious adverse effects were reported. CONCLUSIONS: CHM as an
      adjuvant to anti-TB chemotherapy may have beneficial effect for MDR-TB in terms
      of bacteriological and radiological outcomes, and is relatively safe. However,
      due to poor methodological reporting of the included trials, a confirmative
      conclusion needs to be supported by further robust clinical trials.

PMID- 25861718
TI  - In vitro-in vivo-in silico approach in biopharmaceutical characterization of
      ibuprofen IR and SR tablets.
AB  - Within the last decades, physiologically based pharmacokinetic models have
      emerged into a biopharmaceutical toolkit that has been proven useful in
      understanding how physicochemical, formulation and physiological factors affect
      oral drug absorption. The purpose of this study was to develop a drug specific
      physiologically based pharmacokinetic model that will allow mechanistic
      interpretation of oral absorption from dosage forms exhibiting different in vitro
      and different in vivo performance (i.e. immediate release and sustained release
      tablets) and identification of bioperformance dissolution testing. Ibuprofen was
      chosen to be used for the "proof of concept" considering it is well characterised
      and the necessary physicochemical, biopharmaceutical and pharmacokinetic
      properties for model development could be found in the literature.
      Gastrointestinal simulation technology implemented in Simcyp(r) was successful in
      estimating ibuprofen oral absorption. The developed model exhibited good
      generalisation ability for the dosage forms studied. The obtained results
      indicate that the model was sensitive to input kinetics represented by the in
      vitro drug release profiles obtained under various dissolution conditions.
      According to the obtained results, reciprocating cylinder apparatus with
      biorepresentative change in media pH might be considered as bioperformance
      dissolution in the case of the two ibuprofen SR products studied. These results
      further justify the use of integrated in vitro-in vivo-in silico approach in
      estimating bioperformance of oral solid dosage forms. 

PMID- 25861719
TI  - Preparation, characterization and in vivo studies of amorphous solid dispersion
      of berberine with hydrogenated phosphatidylcholine.
AB  - Berberine, a pure crystalline quaternary ammonium salt with the basic structure
      of isoquinoline alkaloid, has multiple pharmacological bioactivities. But the
      poor bioavailability of berberine limited its wide clinical applications. In the
      present study, we aimed to develop an amorphous solid dispersion of berberine
      with hydrogenated phosphatidylcholine (HPC) in order to improve its
      bioavailability. The physical characterization studies such as differential
      scanning calorimetry (DSC), X-ray powder diffraction (XRPD), Fourier transform
      infrared spectrophotometry (FT-IR) and scanning electron microscopy (SEM) were
      conducted to characterize the formation of amorphous berberine HPC solid
      dispersion (BHPC-SD). The everted intestinal sac and single-pass intestinal
      perfusion study proved that permeability and intestinal absorption of amorphous
      BHPC-SD was improved compared with that of pure crystalline berberine, and the
      pharmacokinetic study results demonstrated that the extent of bioavailability was
      significantly increased as well. However, the dissolution study indicated that
      the aqueous cumulative dissolution percentages of berberine remained unchanged or
      even lower by means of preparation into solid dispersion with HPC. Therefore,
      according to the previous mechanistic studies, the present results supported that
      it is the enhanced molecularly dissolved concentration (supersaturation) of
      berberine by transformation from crystalline structure into amorphous solid
      dispersions that triggers the enhanced permeability, and consequently results in
      the improved intestinal absorption and bioavailability. 

PMID- 25861720
TI  - A review of morphine and morphine-6-glucuronide's pharmacokinetic-pharmacodynamic
      relationships in experimental and clinical pain.
AB  - Morphine is a widely used opioid for treatment of moderate to severe pain, but
      large interindividual variability in patient response and no clear guidance on
      how to optimise morphine dosage regimen complicates treatment strategy for
      clinicians. Population pharmacokinetic-pharmacodynamic models can be used to
      quantify dose-response relationships for the population as well as
      interindividual and interoccasion variability. Additionally, relevant covariates
      for population subgroups that deviate from the typical population can be
      identified and help clinicians in dose optimisation. This review provides a
      detailed overview of the published human population pharmacokinetic
      pharmacodynamic studies for morphine analgesia in addition to basic drug
      disposition and pharmacological properties of morphine and its analgesic active
      metabolite, morphine-6-glucuronide, that may help identify future covariates.
      Furthermore, based on simulations from key pharmacokinetic-pharmacodynamic
      models, the contribution of morphine-6-glucuronide to the analgesic response in
      patients with renal insufficiency was investigated. Simulations were also used to
      examine the impact of effect-site equilibration half-life on time course of
      response. Lastly, the impact of study design on the likelihood of determining
      accurate pharmacodynamic parameters for morphine response was evaluated. 

PMID- 25861721
TI  - Relationships between the risk of cardiovascular disease in type 2 diabetes
      patients and both visit-to-visit variability and time-to-effect differences in
      blood pressure.
AB  - AIMS: To determine whether visit-to-visit blood pressure (BP) variability can
      predict cardiovascular disease (CVD) incidence in type 2 diabetes patients
      independently of mean BP, and to analyze the time-to-effect relationship between
      BP and CVD risk. METHODS: We retrospectively enrolled 629 type 2 diabetes
      patients with no history of CVD who first visited our hospital between 1995 and
      1996, made at least one hospital visit per year, were followed-up for at least 1
      year, and had undergone four or more BP measurements. The patients were followed
      until June 2012 at the latest. RESULTS: CVD occurred in 66 patients. Variability
      in systolic or diastolic BP (SBP and DBP, respectively) was a significant
      predictor of CVD incidence, independent of mean SBP or DBP. CVD incidence was
      significantly associated with SBP during the preceding 3-5 years, with the
      highest risk occurring during the preceding 3 years. CONCLUSIONS: Visit-to-visit
      BP variability independently predicts CVD incidence in type 2 diabetes patients.
      Increased SBP over the preceding 3-5 years indicated a significant CVD risk. To
      prevent CVD, BP management should focus on stable and well-timed control. In
      particular, BP stabilization at an early phase and BP control during late phases
      are important.

PMID- 25861722
TI  - The sub-cellular fate of mercury in the liver of wild mullets (Liza aurata)-
      Contribution to the understanding of metal-induced cellular toxicity.
AB  - Mercury is a recognized harmful pollutant in aquatic systems but still little is
      known about its sub-cellular partitioning in wild fish. Mercury concentrations in
      liver homogenate (whole organ load) and in six sub-cellular compartments were
      determined in wild Liza aurata from two areas - contaminated (LAR) and reference.
      Water and sediment contamination was also assessed. Fish from LAR displayed
      higher total mercury (tHg) organ load as well as in sub-cellular compartments
      than those from the reference area, reflecting environmental differences.
      However, spatial differences in percentage of tHg were only observed for
      mitochondria (Mit) and lysosomes plus microsomes (Lys+Mic). At LAR, Lys+Mic
      exhibited higher levels of tHg than the other fractions. Interestingly, tHg in
      Mit, granules (Gran) and heat-denaturable proteins was linearly correlated with
      the whole organ. Low tHg concentrations in heat stable proteins and Gran suggests
      that accumulated levels might be below the physiological threshold to activate
      those detoxification fractions. 

PMID- 25861723
TI  - Historical trend in heavy metal pollution in core sediments from the Masan Bay,
      Korea.
AB  - The spatiotemporal distribution and their mass accumulation rate (MAR) of heavy
      metals were investigated to evaluate the time-dependent historical trends of
      heavy metal concentration. The three short cores used for this study were
      collected from the catchment area (MS-PC5, 60cm length), the central part (MS
      PC4, 40cm length) and the offshore (MS-PC2, 60cm length) of the Masan Bay, Korea.
      The concentration of heavy metals (Co, Ni, Cu, Zn, Cr and Pb) in catchment area
      is as much as 1.5-2 times higher than central part of the Bay, and about 2 times
      higher than offshore area approximately. In particular, MAR of metals (Cu, Zn and
      Pb) show clear spatiotemporal variation, so that MAR's of heavy metal may provide
      more accurate information in evaluating the degree of pollution. Temporally, the
      heavy metal concentration had been increased since the late 1970s, but it seems
      to decrease again since the 2004yr in catchment area. This may came from
      concentrated efforts for the government to reduce industrial waste release. 

PMID- 25861725
TI  - Genetic patterns of Streptococcus uberis isolated from bovine mastitis.
AB  - The aim of this study was to evaluate the genotypic relationships among 40
      Streptococcus uberis isolated from bovine mastitis by using pulsed-field gel
      electrophoresis (PFGE). Additionally, the association between PFGE patterns and
      virulence profiles was investigated. The isolates exhibited 17 PFGE patterns.
      Different strains were found within and among herds; however, a low number of
      isolates within the same herd shared an identical PFGE type. No association
      between PFGE patterns and virulence profiles was found. However, the detection of
      specific strains in some herds could indicate that some strains are more virulent
      than others. Further research needs to be undertaken to elucidate new virulence
      associated genes that might contribute to the capability of these strains to
      produce infection. 

PMID- 25861726
TI  - Olefins and chemical regulation in Europe: REACH.
AB  - REACH (Registration, Evaluation, Authorisation and Restriction of Chemicals) is
      the European Union's chemical regulation for the management of risk to human
      health and the environment (European Chemicals Agency, 2006). This regulation
      entered into force in June 2007 and required manufacturers and importers to
      register substances produced in annual quantities of 1000 tonnes or more by
      December 2010, with further deadlines for lower tonnages in 2013 and 2018.
      Depending on the type of registration, required information included the
      substance's identification, the hazards of the substance, the potential exposure
      arising from the manufacture or import, the identified uses of the substance, and
      the operational conditions and risk management measures applied or recommended to
      downstream users. Among the content developed to support this information were
      Derived No-Effect Levels or Derived Minimal Effect Levels (DNELs/DMELs) for human
      health hazard assessment, Predicted No Effect Concentrations (PNECs) for
      environmental hazard assessment, and exposure scenarios for exposure and risk
      assessment. Once registered, substances may undergo evaluation by the European
      Chemicals Agency (ECHA) or Member State authorities and be subject to requests
      for additional information or testing as well as additional risk reduction
      measures. To manage the REACH registration and related activities for the
      European olefins and aromatics industry, the Lower Olefins and Aromatics REACH
      Consortium was formed in 2008 with administrative and technical support provided
      by Penman Consulting. A total of 135 substances are managed by this group
      including 26 individual chemical registrations (e.g. benzene, 1,3-butadiene) and
      13 categories consisting of 5-26 substances. This presentation will describe the
      content of selected registrations prepared for 2010 in addition to the
      significant post-2010 activities. Beyond REACH, content of the registrations may
      also be relevant to other European activities, for example consideration of
      worker DNELs/DMELs for occupational exposure level setting, discussion of this
      aspect will be presented for 1,3-butadiene.

PMID- 25861724
TI  - Biomaterial strategies for engineering implants for enhanced osseointegration and
      bone repair.
AB  - Bone tissue has a remarkable ability to regenerate and heal itself. However,
      large bone defects and complex fractures still present a significant challenge to
      the medical community. Current treatments center on metal implants for structural
      and mechanical support and auto- or allo-grafts to substitute long bone defects.
      Metal implants are associated with several complications such as implant
      loosening and infections. Bone grafts suffer from donor site morbidity, reduced
      bioactivity, and risk of pathogen transmission. Surgical implants can be modified
      to provide vital biological cues, growth factors and cells in order to improve
      osseointegration and repair of bone defects. Here we review strategies and
      technologies to engineer metal surfaces to promote osseointegration with the host
      tissue. We also discuss strategies for modifying implants for cell adhesion and
      bone growth via integrin signaling and growth factor and cytokine delivery for
      bone defect repair. 

PMID- 25861727
TI  - MiRNA-21 silencing mediated by tumor-targeted nanoparticles combined with
      sunitinib: A new multimodal gene therapy approach for glioblastoma.
AB  - Malignant brain tumors, including glioblastoma (GBM), are among the most lethal
      human cancers, due to their tremendous invasive capacity and limited therapeutic
      options. Despite remarkable advances in cancer theranostics, which resulted in
      significant improvement of clinical outcomes, GBM relapse is very frequent and
      patient survival remains under one year. The elucidation of the role of
      abnormally-expressed miRNAs in different steps of GBM pathogenesis and in tumor
      resistance to therapy paved the way for the development of new miRNA-based
      therapeutic approaches targeting this disease, aiming at increasing specific
      tumor cell killing and, ultimately, cancer eradication. Here, we demonstrate that
      intravenously-administered chlorotoxin (CTX)-coupled (targeted) stable nucleic
      acid lipid particle (SNALP)-formulated anti-miR-21 oligonucleotides accumulate
      preferentially within brain tumors and promote efficient miR-21 silencing, which
      results in increased mRNA and protein levels of its target RhoB, while showing no
      signs of systemic immunogenicity. Decreased tumor cell proliferation and tumor
      size, as well as enhanced apoptosis activation and, to a lesser extent,
      improvement of animal survival, were also observed in GBM-bearing mice upon
      systemic delivery of targeted nanoparticle-formulated anti-miR-21
      oligonucleotides and exposure to the tyrosine kinase inhibitor sunitinib.
      Overall, our results provide evidence that CTX-coupled SNALPs are a reliable and
      efficient system for systemic delivery of anti-miRNA oligonucleotides. Moreover,
      although further studies are still necessary to demonstrate a therapeutic benefit
      in a clinical context, our findings suggest that miRNA modulation by the targeted
      nanoparticles combined with anti-angiogenic chemotherapy may hold promise as an
      attractive approach towards GBM treatment. 

PMID- 25861728
TI  - Liposomal delivery systems for anti-cancer analogues of vitamin E.
AB  - Pro-apoptotic analogues of vitamin E (VE) exert selective anti-cancer effect on
      various animal cancer models. Neither suitable formulation of alpha-tocopheryl
      succinate (alpha-TOS), representative semi-synthetic VE analogue ester, nor
      suitable formulations of the other VE analogues for clinical application have
      been reported yet. The major factor limiting the use of VE analogues is their low
      solubility in aqueous solvents. Due to the hydrophobic character of VE analogues,
      liposomes are predetermined as suitable delivery system. Liposomal formulation
      prevents undesirable side effects of the drug, enhances the drug
      biocompatibility, and improves the drug therapeutic index. Liposomal formulations
      of VE analogues especially of alpha-TOS and alpha-tocopheryl ether linked acetic
      acid (alpha-TEA) have been developed. The anti-cancer effect of these liposomal
      VE analogues has been successfully demonstrated in pre-clinical models in vivo.
      Present achievements in: (i) preparation of liposomal formulations of VE
      analogues, (ii) physico-chemical characterization of these developed systems and
      (iii) testing of their biological activity such as induction of apoptosis and
      evaluation of anti-cancer effect are discussed in this review. 

PMID- 25861729
TI  - Activated expression of AtWRKY53 negatively regulates drought tolerance by
      mediating stomatal movement.
AB  - KEY MESSAGE: AtWRKY53 is an early factor in drought response and activated
      expression of AtWRKY53 regulates stomatal movement via reduction of H 2 O 2
      content and promotion of starch metabolism in guard cells. Drought is one of the
      most serious environmental factors limiting the productivity of agricultural
      crops worldwide. However, the mechanisms underlying drought tolerance in plants
      remain unclear. AtWRKY53 belongs to the group III of WRKY transcription factors.
      In this study, we observed both the mRNA and protein products of this gene are
      rapidly induced under drought conditions. Phenotypic analysis showed AtWRKY53
      overexpression lines were hypersensitive to drought stress compared with Col-0
      plants. The results of stomatal movement assays and abscisic acid (ABA) content
      detection indicated that the impaired stomatal closure of 53OV lines was
      independent of ABA. Further analysis found that WRKY53 regulated stomatal
      movement via reducing the H2O2 content and promoting the starch metabolism in
      guard cells. The results of quantitative real-time reverse transcriptase PCR
      showed that the expression levels of CAT2, CAT3 and QQS were up-regulated in 53OV
      lines. Chromatin immunoprecipitation assays demonstrated that AtWRKY53 can
      directly bind to the QQS promoter sequences, thus led to increased starch
      metabolism. In summary, our results indicated that the activated expression of
      AtWRKY53 inhibited stomatal closure by reducing H2O2 content and facilitated
      stomatal opening by promoting starch degradation.

PMID- 25861730
TI  - The major histocompatibility complex genes impact pain response in DA and DA.1U
      rats.
AB  - Our recent studies have shown that the difference in basal pain sensitivity to
      mechanical and thermal stimulation between Dark-Agouti (DA) rats and a novel
      congenic DA.1U rats is major histocompatibility complex (MHC) genes dependent. In
      the present study, we further used DA and DA.1U rats to investigate the role of
      MHC genes in formalin-induced pain model by behavioral, electrophysiological and
      immunohistochemical methods. Behavioral results showed biphasic nociceptive
      behaviors increased significantly following the intraplantar injection of
      formalin in the hindpaw of DA and DA.1U rats. The main nociceptive behaviors were
      lifting and licking, especially in DA rats (P<0.001 and P<0.01). The composite
      pain scores (CPS) in DA rats were significantly higher than those in DA.1U rats
      in both phases of the formalin test (P<0.01). Electrophysiological results also
      showed the biphasic increase in discharge rates of C and Adelta fibers of L5
      dorsal root in the two strains, and the net change of the discharge rate of DA
      rats was significantly higher than that of DA.1U rats (P<0.05). The mechanical
      thresholds decreased after formalin injection in both strains (P<0.01), and the
      net change in the mechanical threshold in DA was greater than that in DA.1U rats
      (P<0.05). The expression of RT1-B, representation of MHC class II molecule, in
      laminae I-II of L4/5 spinal cord in DA rats was significantly higher than that in
      DA.1U rats in the respective experimental group (P<0.05). These results suggested
      that both DA and DA.1U rats exhibited nociceptive responses in formalin-induced
      pain model and DA rats were more sensitive to noxious chemical stimulus than
      DA.1U rats, indicating that MHC genes might contribute to the difference in pain
      sensitivity. 

PMID- 25861732
TI  - Genome-wide comparison of ultraviolet and ethyl methanesulphonate mutagenesis
      methods for the brown alga Ectocarpus.
AB  - Ectocarpus has emerged as a model organism for the brown algae and a broad range
      of genetic and genomic resources are being generated for this species. The aim of
      the work presented here was to evaluate two mutagenesis protocols based on
      ultraviolet irradiation and ethyl methanesulphonate treatment using genome
      resequencing to measure the number, type and distribution of mutations generated
      by the two methods. Ultraviolet irradiation generated a greater number of genetic
      lesions than ethyl methanesulphonate treatment, with more than 400 mutations
      being detected in the genome of the mutagenised individual. This study therefore
      confirms that the ultraviolet mutagenesis protocol is suitable for approaches
      that require a high density of mutations, such as saturation mutagenesis or
      Targeting Induced Local Lesions in Genomes (TILLING). 

PMID- 25861731
TI  - Developmental Change in the Effects of Sexual Partner and Relationship
      Characteristics on Sexual Risk Behavior in Young Men Who Have Sex with Men.
AB  - Young men who have sex with men are substantially impacted by HIV/AIDS, and most
      new infections occur in serious romantic dyads. Young people experience
      substantial psychosocial and neurocognitive change between adolescence and
      emerging adulthood which impacts engagement in risk behaviors. We aimed to
      examine developmental change in the association between sexual partnership
      characteristics and condomless anal intercourse (CAI). Data were taken from an
      analytic sample of 114 young adult MSM from a longitudinal study of lesbian, gay,
      bisexual and transgender youth with 4-year follow-up. Rates of CAI were
      approximately 12 times higher in serious compared to casual partnerships, but
      this effect diminished in size over time. Partner age differences and violence
      were associated with more CAI, and these associations strengthened across
      development. Characteristics of serious relationships (e.g., power dynamics) were
      also examined. We discuss the need for HIV prevention strategies that address
      dyadic influences on CAI during this critical developmental period.

PMID- 25861733
TI  - Draft genome of Marinomonas sp. BSi20584 from Arctic sea ice.
AB  - Life surviving in extremely cold frozen environments has been largely
      uninvestigated. Here we described the draft genome of Marinomonas sp. BSi20584,
      isolated from Arctic sea ice in the Canada Basin. The assembled genome comprised
      4.85Mb, with the G+C content of 42.6%. Single copy of rRNA operon was detected,
      which may increase fitness in cold and nutrient-limited environment. In addition,
      BSi20584 may also use universal strategies for cold adaptation as indicated by
      the genome. Abundant genes responsible for decomposition of aromatic hydrocarbons
      were detected, which suggested potential biotechnological applications. The first
      genomic analysis of Marinomonas in Arctic sea ice provided primary genetic
      information and encouraged further research on comparative genomics and
      biotechnological applications. 

PMID- 25861734
TI  - Improved reliability, accuracy and quality in automated NMR structure calculation
      with ARIA.
AB  - In biological NMR, assignment of NOE cross-peaks and calculation of atomic
      conformations are critical steps in the determination of reliable high-resolution
      structures. ARIA is an automated approach that performs NOE assignment and
      structure calculation in a concomitant manner in an iterative procedure. The log
      harmonic shape for distance restraint potential and the Bayesian weighting of
      distance restraints, recently introduced in ARIA, were shown to significantly
      improve the quality and the accuracy of determined structures. In this paper, we
      propose two modifications of the ARIA protocol: (1) the softening of the force
      field together with adapted hydrogen radii, which is meaningful in the context of
      the log-harmonic potential with Bayesian weighting, (2) a procedure that
      automatically adjusts the violation tolerance used in the selection of active
      restraints, based on the fitting of the structure to the input data sets. The new
      ARIA protocols were fine-tuned on a set of eight protein targets from the CASD
      NMR initiative. As a result, the convergence problems previously observed for
      some targets was resolved and the obtained structures exhibited better quality.
      In addition, the new ARIA protocols were applied for the structure calculation of
      ten new CASD-NMR targets in a blind fashion, i.e. without knowing the actual
      solution. Even though optimisation of parameters and pre-filtering of unrefined
      NOE peak lists were necessary for half of the targets, ARIA consistently and
      reliably determined very precise and highly accurate structures for all cases. In
      the context of integrative structural biology, an increasing number of
      experimental methods are used that produce distance data for the determination of
      3D structures of macromolecules, stressing the importance of methods that
      successfully make use of ambiguous and noisy distance data. 

PMID- 25861736
TI  - Loop-mediated isothermal amplification (LAMP) based detection of Colletotrichum
      falcatum causing red rot in sugarcane.
AB  - Red rot, caused by Colletotrichum falcatum, is a destructive disease prevalent in
      most sugarcane-producing countries. Disease-free sugarcane planting materials
      (setts) are essential as the pathogen spreads primarily through infected setts.
      The present study was undertaken to develop a loop-mediated isothermal
      amplification (LAMP) assay for the detection of C. falcatum. C. falcatum genomic
      DNA was isolated from pure mycelium culture and infected tissues. Four sets of
      primers corresponding to a unique DNA sequence specific to C. falcatum were
      designed. Specificity of the LAMP test was checked with DNA of another fungal
      pathogen of sugarcane, Puccinia melanocephala, as well as two closely-related
      species, Colletotrichum fructivorum and Colletotrichum acutatum. No reaction was
      found with the three pathogens. When C. falcatum DNA from pure culture was used
      in a detection limit analysis, sensitivity of the LAMP method was observed to be
      ten times higher than that of conventional PCR; however, sensitivity was only 5
      times higher when DNA from C. falcatum-infected tissues was used. Using the LAMP
      assay, C. falcatum DNA is amplified with high specificity, efficiency, and
      rapidity under isothermal conditions. Moreover, visual judgment of color change
      in <1 h without further post-amplification processing makes the LAMP method
      convenient, economical, and useful in diagnostic laboratories and the field. 

PMID- 25861735
TI  - Functional constituents of a local serotonergic system, intrinsic to the human
      coronary artery smooth muscle cells.
AB  - Human coronary artery smooth muscle cells (HCASMCs) play an important role in the
      pathogenesis of coronary atherosclerosis and coronary artery diseases (CAD).
      Serotonin is a mediator known to produce vascular smooth muscle cell mitogenesis
      and contribute to coronary atherosclerosis. We hypothesize that the HCASMC
      possesses certain functional constituents of the serotonergic system such as:
      tryptophan hydroxylase and serotonin transporter. Our aim was to examine the
      presence of functional tryptophan hydroxylase-1 (TPH1) and serotonin transporter
      (SERT) in HCASMCs. The mRNA transcripts by qPCR and protein expression by Western
      blot of TPH1 and SERT were examined. The specificity and accuracy of the primers
      were verified using DNA gel electrophoresis and sequencing of qPCR products. The
      functionality of SERT was examined using a fluorescence dye-based serotonin
      transporter assay. The enzymatic activity of TPH was evaluated using UPLC. The
      HCASMCs expressed both mRNA transcripts and protein of SERT and TPH. The qPCR
      showed a single melt curve peak for both transcripts and in sequence analysis the
      amplicons were aligned with the respective genes. SERT and TPH enzymatic activity
      was present in the HCASMCs. Taken together, both TPH and SERT are functionally
      expressed in HCASMCs. These findings are novel and represent an initial step in
      examining the clinical relevance of the serotonergic system in HCASMCs and its
      role in the pathogenesis of coronary atherosclerosis and CAD. 

PMID- 25861737
TI  - Efficacy of BI 671800, an oral CRTH2 antagonist, in poorly controlled asthma as
      sole controller and in the presence of inhaled corticosteroid treatment.
AB  - The prostaglandin D2 (PGD2) receptor, CRTH2, plays a role in allergic airway
      inflammation. The efficacy of BI 671800, a CRTH2 antagonist, was assessed in 2
      separate trials in patients with asthma, in either the absence or the presence of
      inhaled corticosteroid (ICS) therapy. In this study, BI 671800 (50, 200 or 400
      mg) and fluticasone propionate (220 MUg) all given twice daily (bid) were
      compared with bid placebo in symptomatic controller-naive adults with asthma
      (Trial 1), and BI 671800 400 mg bid compared with montelukast 10 mg once daily
      (qd), and matching placebo bid, in patients with asthma receiving inhaled
      fluticasone (88 MUg bid) (Trial 2). The primary endpoint in both trials was
      change from baseline in trough forced expiratory volume in 1 s (FEV1) percent
      predicted. After 6 weeks' treatment, adjusted mean treatment differences (SE) for
      the primary endpoint compared with placebo in Trial 1 were 3.08% (1.65%), 3.59%
      (1.60%) and 3.98% (1.64%) for BI 671800 50, 200 and 400 mg bid, respectively, and
      8.62% (1.68%) for fluticasone 220 MUg bid (p = 0.0311, p = 0.0126, p = 0.0078 and
      p < 0.0001, respectively). In Trial 2, adjusted mean FEV1 (SE) treatment
      differences compared with placebo were 3.87% (1.49%) for BI 671800 400 mg bid and
      2.37% (1.57%) for montelukast (p = 0.0050 and p = 0.0657, respectively). These
      findings suggest that BI 671800 is associated with a small improvement in FEV1 in
      symptomatic controller-naive asthma patients, and in patients on ICS.

PMID- 25861738
TI  - A morphometric analysis of contralateral neural foramen in TLIF.
AB  - STUDY DESIGN: A retrospective review PURPOSE: This study was designed to compare
      postoperative changes in neural foramen between transforaminal lumbar interbody
      fusion (TLIF) and posterior lumbar interbody fusion (PLIF). METHODS: A
      retrospective analysis of 67 patients was compared to the change of neural
      foraminal morphometry of the two techniques. 33 patients (40 levels) had TLIF and
      34 patients (39 levels) had PLIF. The two groups had similar demographic
      profiles. Radiological parameters including anterior and posterior disc height,
      foraminal height (FH), and segmental Cobb angle (SCA) were measured by sagittally
      reconstructed computed tomography images before and after surgery. Cage position
      was designated as contralateral, middle, and ipsilateral in the TLIF group.
      Surgical results were assessed by Odom criteria, visual analog scale (VAS), and
      Oswestry disability index (ODI) scores. RESULTS: The TLIF and PLIF group showed
      no bilateral difference in FH. The TLIF group had increased contralateral SCA
      compared to the ipsilateral side postoperatively. FH differed according to cage
      position in the TLIF group. When a cage was inserted deeply into the
      contralateral side, contralateral FH increased significantly. However, when a
      cage was inserted into the ipsilateral side, contralateral FH decreased
      significantly. Back pain was significantly lower in the TLIF group at 1 and 6
      months than in the PLIF group. However, ODI and Odom scale scores were not
      different between the groups. CONCLUSIONS: TLIF may induce uneven changes in
      foraminal morphometry. Cage position may be the major determinant of this result.

PMID- 25861739
TI  - Incidence of vascular complications during lateral lumbar interbody fusion: an
      examination of the mini-open access technique.
AB  - PURPOSE: This article examines the incidence and management of vascular injury
      during Lateral Lumbar Interbody Fusion (LLIF). The details of the mini-open
      access technique are presented. METHODS: A total of 900 patients who underwent a
      LLIF at an average 1.94 levels (range: 1-5 levels) by one of six fellowship
      trained surgeons on 1,754 levels from 2006 to 2013 were identified. The incidence
      of intraoperative vascular injury was retrospectively determined from the
      Operative Records. The management of vascular injury was evaluated. The mini-open
      access adapted by our institution for LLIF is described. RESULTS: The incidence
      of major vascular complication in our series was 1/900. The incidence of minor
      vascular injury was 4/900. The overall incidence of vascular injury was
      calculated to be 0.056 % per case and 0.029 % per level. All minor vascular
      injuries were identified to be segmental vessel lacerations, which were readily
      ligated under direct visualization without further extension of the incision with
      no clinical sequelae. The laceration of the abdominal aorta, the major vascular
      complication of this series, was emergently repaired through an exploratory
      laparotomy. None of the patients suffered long-term sequelae from their
      intraoperative vascular injuries. CONCLUSIONS: The mini-open lateral access
      technique for LLIF provides for minimal risk of vascular injury to the lumbar
      spine. In the rare event of minor vascular injury, the mini-open access approach
      allows for immediate visualization, confirmation and repair of the vessel with no
      long-term sequelae.

PMID- 25861740
TI  - Preparation, characterization and antibacterial activity of octenyl succinic
      anhydride modified inulin.
AB  - Octenyl succinic anhydride modified inulin (In-OSA) was synthesized via chemical
      modification of inulin with octenyl succinic anhydride (OSA). The esterification
      of inulin with OSA was confirmed by Fourier transform infrared spectroscopy (FT
      IR), scanning electron microscopy (SEM), and degree of substitution (DS)
      calculation. Antibacterial activity of In-OSA against Staphylococcus aureus and
      Escherichia coli was investigated by minimum inhibitory concentration (MIC) and
      inhibition rate determination. The results showed that inhibition rates against
      both E.coli and S. aureus increased with the increase of the In-OSA
      concentration. And the MICs against E. coli and S. aureus were 1% and 0.5% (w/v),
      respectively. The antibacterial mechanism was analyzed with the results of the
      proteins and nucleic acids leakage, SEM and negative staining transmission
      electron microscopy (TEM). Both the leakages of proteins and nucleic acids
      increased with the increase of the In-OSA concentration. The leakage occurred
      mainly in the early stage which indicated that cell membrane and wall were
      destroyed by In-OSA quickly. The images of SEM and negative staining TEM
      suggested that the cell membranes and cell walls of S. aureus were damaged more
      severely and even destroyed completely; but only pores appeared on the surface of
      E. coli. 

PMID- 25861741
TI  - Alginate gel-coated oil-entrapped alginate-tamarind gum-magnesium stearate
      buoyant beads of risperidone.
AB  - A novel alginate gel-coated oil-entrapped calcium-alginate-tamarind gum (TG)
      magnesium stearate (MS) composite floating beads was developed for intragastric
      risperidone delivery with a view to improving its oral bioavailability. The TG
      blended alginate core beads containing olive oil and MS as low-density materials
      were accomplished by ionotropic gelation technique. Effects of polymer-blend
      ratio (sodium alginate:TG) and crosslinker (CaCl2) concentration on drug
      entrapment efficiency (DEE, %) and cumulative drug release after 8 h (Q8h, %)
      were studied to optimize the core beads by a 3(2) factorial design. The optimized
      beads (F-O) exhibited DEE of 75.19+/-0.75% and Q8h of 78.04+/-0.38% with minimum
      errors in prediction. The alginate gel-coated optimized beads displayed superior
      buoyancy and sustained drug release property. The drug release profiles of the
      drug-loaded uncoated and coated beads were best fitted in Higuchi kinetic model
      with Fickian and anomalous diffusion driven mechanisms, respectively. The
      optimized beads yielded a notable sustained drug release profile as compared to
      marketed immediate release preparation. The uncoated and coated Ca-alginate-TG-MS
      beads were also characterized by SEM, FTIR and P-XRD analyses. Thus, the newly
      developed alginate-gel coated oil-entrapped alginate-TG-MS composite beads are
      suitable for intragastric delivery of risperidone over a prolonged period of
      time.

PMID- 25861742
TI  - Study the effect of His-tag on chondroitinase ABC I based on characterization of
      enzyme.
AB  - Chondroitinase ABC I (ChSase ABC I) which could degrade chondroitin sulfate (CS)
      to low molecular weight CS was expressed with His-tag in Escherichia coli (E.
      coli) BL21(DE3). The effect of His-tag on ChSase ABC I was investigated compared
      with ChSase ABC I which cut His-tag for the first time. After three steps
      purification, the specific activity of His-ChSase ABC I was 201.9+/-5.4 IU/mg
      which was two times lower than ChSase ABC I. Results of multi angle light
      scattering (MALS) and analytical ultracentrifugation (AUC) showed that the
      polymeric state of His-ChSase ABC I was not effected by His-tag and it was
      monomer, and ChSase ABC I was the same. The optimal temperature and pH of His
      ChSase ABC I were 37  degrees C and 7.5, and were almost same with ChSase ABC I.
      Vmax and kcat/Km of His-ChSase ABC I were 2.4+/-0.1 MUmol/Ls, and 22.2+/-0.4
      L/(MUmols) and catalytic efficiency was lower than ChSase ABC I. Generally, His
      tag had no effect on polymeric state, optimal temperature and pH, had little
      negative impact on specific activity, kcat/Km and secondary-structure of ChSase
      ABC I. This study might guide the application of ChSase ABC I in industrial
      production.

PMID- 25861743
TI  - Generation and functions of second messengers microdomains.
AB  - A compelling example of the mechanisms by which the cells can organize and
      decipher complex and different functional activities is the convergence of a
      multitude of stimuli into signalling cascades, involving only few intracellular
      second messengers. The possibility of restricting these signalling events in
      distinct microdomains allows a fine and selective tuning of very different tasks.
      In this review, we will discuss the mechanisms that control the formation and the
      spatial distribution of Ca(2+) and cAMP microdomains, providing some examples of
      their functional consequences. 

PMID- 25861744
TI  - Stress-induced dissociations between intracellular calcium signaling and insulin
      secretion in pancreatic islets.
AB  - In healthy pancreatic islets, glucose-stimulated changes in intracellular calcium
      ([Ca(2+)]i) provide a reasonable reflection of the patterns and relative amounts
      of insulin secretion. We report that [Ca(2+)]i in islets under stress, however,
      dissociates with insulin release in different ways for different stressors.
      Islets were exposed for 48h to a variety of stressors: cytokines (low-grade
      inflammation), 28mM glucose (28G, glucotoxicity), free fatty acids (FFAs,
      lipotoxicity), thapsigargin (ER stress), or rotenone (mitochondrial stress). We
      then measured [Ca(2+)]i and insulin release in parallel studies. Islets exposed
      to all stressors except rotenone displayed significantly elevated [Ca(2+)]i in
      low glucose, however, increased insulin secretion was only observed for 28G due
      to increased nifedipine-sensitive calcium-channel flux. Following 3-11mM glucose
      stimulation, all stressors substantially reduced the peak glucose-stimulated
      [Ca(2+)]i response (first phase). Thapsigargin and cytokines also substantially
      impacted aspects of calcium influx and ER calcium handling. Stressors did not
      significantly impact insulin secretion in 11mM glucose for any stressor, although
      FFAs showed a borderline reduction, which contributed to a significant decrease
      in the stimulation index (11:3mM glucose) observed for FFAs and also for 28G. We
      also clamped [Ca(2+)]i using 30mM KCl+250MUM diazoxide to test the amplifying
      pathway. Only rotenone-treated islets showed a robust increase in 3-11mM glucose
      stimulated insulin secretion under clamped conditions, suggesting that low-level
      mitochondrial stress might activate the metabolic amplifying pathway. We conclude
      that different stressors dissociate [Ca(2+)]i from insulin secretion differently:
      ER stressors (thapsigargin, cytokines) primarily affect [Ca(2+)]i but not
      conventional insulin secretion and 'metabolic' stressors (FFAs, 28G, rotenone)
      impacted insulin secretion.

PMID- 25861746
TI  - Upper-limb kinematic reconstruction during stroke robot-aided therapy.
AB  - The paper proposes a novel method for an accurate and unobtrusive reconstruction
      of the upper-limb kinematics of stroke patients during robot-aided rehabilitation
      tasks with end-effector machines. The method is based on a robust analytic
      procedure for inverse kinematics that simply uses, in addition to hand pose data
      provided by the robot, upper arm acceleration measurements for computing a
      constraint on elbow position; it is exploited for task space augmentation. The
      proposed method can enable in-depth comprehension of planning strategy of stroke
      patients in the joint space and, consequently, allow developing therapies
      tailored for their residual motor capabilities. The experimental validation has a
      twofold purpose: (1) a comparative analysis with an optoelectronic motion
      capturing system is used to assess the method capability to reconstruct joint
      motion; (2) the application of the method to healthy and stroke subjects during
      circle-drawing tasks with InMotion2 robot is used to evaluate its efficacy in
      discriminating stroke from healthy behavior. The experimental results have shown
      that arm angles are reconstructed with a RMSE of 8.3 * 10(-3) rad. Moreover, the
      comparison between healthy and stroke subjects has revealed different features in
      the joint space in terms of mean values and standard deviations, which also allow
      assessing inter- and intra-subject variability. The findings of this study
      contribute to the investigation of motor performance in the joint space and
      Cartesian space of stroke patients undergoing robot-aided therapy, thus allowing:
      (1) evaluating the outcomes of the therapeutic approach, (2) re-planning the
      robotic treatment based on patient needs, and (3) understanding pathology-related
      motor strategies.

PMID- 25861745
TI  - Bacteriophage and their potential roles in the human oral cavity.
AB  - The human oral cavity provides the perfect portal of entry for viruses and
      bacteria in the environment to access new hosts. Hence, the oral cavity is one of
      the most densely populated habitats of the human body containing some 6 billion
      bacteria and potentially 35 times that many viruses. The role of these viral
      communities remains unclear; however, many are bacteriophage that may have active
      roles in shaping the ecology of oral bacterial communities. Other implications
      for the presence of such vast oral phage communities include accelerating the
      molecular diversity of their bacterial hosts as both host and phage mutate to
      gain evolutionary advantages. Additional roles include the acquisitions of new
      gene functions through lysogenic conversions that may provide selective
      advantages to host bacteria in response to antibiotics or other types of
      disturbances, and protection of the human host from invading pathogens by binding
      to and preventing pathogens from crossing oral mucosal barriers. Recent evidence
      suggests that phage may be more involved in periodontal diseases than were
      previously thought, as their compositions in the subgingival crevice in moderate
      to severe periodontitis are known to be significantly altered. However, it is
      unclear to what extent they contribute to dysbiosis or the transition of the
      microbial community into a state promoting oral disease. Bacteriophage
      communities are distinct in saliva compared to sub- and supragingival areas,
      suggesting that different oral biogeographic niches have unique phage ecology
      shaping their bacterial biota. In this review, we summarize what is known about
      phage communities in the oral cavity, the possible contributions of phage in
      shaping oral bacterial ecology, and the risks to public health oral phage may
      pose through their potential to spread antibiotic resistance gene functions to
      close contacts. 

PMID- 25861747
TI  - The connection between cellular mechanoregulation and tissue patterns during bone
      healing.
AB  - The formation of different tissues in the callus during secondary bone healing is
      at least partly influenced by mechanical stimuli. We use computer simulations to
      test the consequences of different hypotheses of the mechanoregulation at the
      cellular level on the patterns of tissues formed during healing. The
      computational study is based on an experiment on sheep, where after a tibial
      osteotomy, histological sections were harvested at different time points. In the
      simulations, we used a recently proposed basic phenomenological model, which
      allows ossification to occur either via endochondral or intramembranous
      ossification, but tries otherwise to employ a minimal number of simulation
      parameters. The model was extended to consider also the possibility of bone
      resorption and consequently allowing a description of the full healing
      progression till the restoration of the cortex. Specifically, we investigated how
      three changes in the mechanoregulation influence the resulting tissue patterns:
      (1) a time delay between stimulation of the cell and the formation of the tissue,
      (2) a variable mechanosensitivity of the cells, and (3) an independence of long
      time intervals of the soft tissue maturation from the mechanical stimulus. For
      all three scenarios, our simulations do not show qualitative differences in the
      time development of the tissue patterns. Largest differences were observed in the
      intermediate phases of healing in the amount and location of the cartilage.
      Interestingly, the course of healing was virtually unaltered in case of scenario
      (3) where tissue maturation proceeded independent of mechanical stimulation. 

PMID- 25861748
TI  - Three new prenylated flavonoids from Macaranga denticulata and their anticancer
      effects.
AB  - One rare flavonoid-diterpene heterodimer, denticulatain C (1), one modified
      geranyl-type side chain substituted flavonoid, denticulatain D (2) and one
      geranylated flavonoid, denticulatain E (3), as well as 11 known compounds (4-14)
      were isolated from the fronds of Macaranga denticulata. Their structures were
      elucidated on the basis of extensive spectroscopic interpretation. Compounds 4
      and 8 inhibited the proliferation of A-549 cell line with IC50 values of 48.6 and
      20.2 MUg/mL, respectively. Compounds 3, 6, and 8 exhibited significant
      antiangiogenic activity on a zebrafish model with IC50 values of 9.78, 0.34, and
      2.55 MUg/mL, respectively.

PMID- 25861749
TI  - Cytotoxic prenylated flavonoids from Macaranga indica.
AB  - Three new prenylated flavonoids, macarindicins A-C (1-3), as well as seven known
      compounds (4-10) were isolated from the twigs of Macaranga indica. Their
      structures were elucidated on the basis of extensive spectroscopic
      interpretation. Compounds 2 and 3 enriched the diversity of prenyl moiety in
      genus Macaranga especially in the aspect of various lengths of prenyl chain. All
      the known compounds were isolated from M. indica for the first time and this
      plant was found to contain large number of ellagic acid. Compounds 1-10 were
      tested for their cytotoxicity against four cancer cell lines (MCF-7, Hep G2, Hela
      and P388) and showed IC50 values in the range of 2.61-20.35 MUg/mL.

PMID- 25861750
TI  - The impact of within-herd genetic variation upon inferred transmission trees for
      foot-and-mouth disease virus.
AB  - Full-genome sequences have been used to monitor the fine-scale dynamics of
      epidemics caused by RNA viruses. However, the ability of this approach to
      confidently reconstruct transmission trees is limited by the knowledge of the
      genetic diversity of viruses that exist within different epidemiological units.
      In order to address this question, this study investigated the variability of 45
      foot-and-mouth disease virus (FMDV) genome sequences (from 33 animals) that were
      collected during 2007 from eight premises (10 different herds) in the United
      Kingdom. Bayesian and statistical parsimony analysis demonstrated that these
      sequences exhibited clustering which was consistent with a transmission scenario
      describing herd-to-herd spread of the virus. As an alternative to analysing all
      of the available samples in future epidemics, the impact of randomly selecting
      one sequence from each of these herds was used to assess cost-effective methods
      that might be used to infer transmission trees during FMD outbreaks. Using these
      approaches, 85% and 91% of the resulting topologies were either identical or
      differed by only one edge from a reference tree comprising all of the sequences
      generated within the outbreak. The sequence distances that accrued during
      sequential transmission events between epidemiological units was estimated to be
      4.6 nucleotides, although the genetic variability between viruses recovered from
      chronic carrier animals was higher than between viruses from animals with acute
      stage infection: an observation which poses challenges for the use of simple
      approaches to infer transmission trees. This study helps to develop strategies
      for sampling during FMD outbreaks, and provides data that will guide the
      development of further models to support control policies in the event of virus
      incursions into FMD free countries.

PMID- 25861751
TI  - miR-124 represses FZD5 to attenuate P-glycoprotein-mediated chemo-resistance in
      renal cell carcinoma.
AB  - Renal cell carcinoma (RCC) is one of most malignant neoplasms, exhibiting poor
      responsiveness to the conventional chemo-regime. Abnormal expression of P
      glycoprotein (P-gp) has been implicated in the emergence of multiple-drug
      resistance (MDR) by reducing the accumulation of intracellular chemotherapy
      drugs. Wnt signaling plays critical roles in renal cancer and is triggered by
      binding of Wnt ligands to Frizzled (FZD) receptor proteins. miR-124 is a tumor
      suppressor associated with cancer relapse and MDR, whereas its role in P-gp
      mediated MDR in refractory RCC is as yet unrevealed. Our study aimed to
      investigate the roles of miR-124 in chemo-resistant RCC cells and the potential
      targeted signaling paths in inducing P-gp expression. Doxorubicin (DOX)- and
      vinblastine (VBL)-resistant Caki-2 cells were developed by exposure of parental
      Caki-2 cells to the agents over a long period of time. In comparison with their
      parental cells, miR-124 was downregulated in Caki-2/DOX and Caki-2/VBL cells,
      accompanied by increased FZD5 and P-gp. IC50 values were reduced significantly
      after miR-124 mimics were introduced into Caki-2/DOX cells. In addition, miR-124
      mimics significantly promoted apoptosis of Caki-2/DOX cells. miR-124 targeted to
      FZD5 and miR-124 mimics as well as FZD5 siRNA showed significant inhibitory
      effects on P-gp expression in Caki-2/DOX cells. Furthermore, Wnt-5a dose
      dependently stimulated the presentation of p-PKCalpha/betaII and p-CamKII via
      activating FZD5, which was reversed by FZD5 silencing. Moreover, FZD5/protein
      kinase C (PKC) signaling is responsible for the elevation of P-gp and cancer cell
      survival. In conclusion, restoring miR-124 may function as a promising strategy
      to overcome P-gp-mediated MDR by inhibiting FZD5/PKC signaling.

PMID- 25861752
TI  - Involvement of multiple cellular pathways in regulating resistance to tamoxifen
      in BIK-suppressed MCF-7 cells.
AB  - Majority of women with estrogen receptor (ER)-positive breast cancers initially
      respond to hormone therapies such as tamoxifen (TAM; antagonist of estrogen).
      However, many tumors eventually become resistant to TAM. Therefore, understanding
      the various cellular components involved in causing resistance to TAM is of
      paramount importance in designing novel entities for efficacious hormone therapy.
      Previously, we found that suppression of BIK gene expression induced TAM
      resistance in MCF-7 breast cancer cells. In order to understand the response of
      these cells to TAM and its association with resistance, a microarray analysis of
      gene expression was performed in the BIK-suppressed MCF-7 cells and compared it
      to the TAM-only-treated cells (controls). Several genes participating in various
      cellular pathways were identified. Molecules identified in the drug resistance
      pathway were 14-3-3z or YWHAZ, WEE1, PRKACA, NADK, and HSP90AA 1. Further, genes
      involved in cell cycle control, apoptosis, and cell proliferation were also found
      differentially expressed in these cells. Transcriptional and translational
      analysis of key molecules such as STAT2, AKT 3, and 14-3-3z revealed similar
      changes at the messenger RNA (mRNA) as well as at the protein level. Importantly,
      there was no cytotoxic effect of TAM on BIK-suppressed MCF-7 cells. Further,
      these cells were not arrested at the G0-G1 phase of the cell cycle although 30 %
      of BIK-suppressed cells were arrested at the G2 phase of the cycle on TAM
      treatment. Furthermore, we found a relevant interaction between 14-3-3z and WEE1,
      suggesting that the cytotoxic effect of TAM was prevented in BIK-suppressed cells
      because this interaction leads to transitory arrest in the G2 phase leading to
      the repair of damaged DNA and allowing the cells to proliferate.

PMID- 25861753
TI  - Genetic polymorphisms of the multidrug resistance 1 gene MDR1 and the risk of
      hepatocellular carcinoma.
AB  - A possible association between multiple drug resistance 1 gene (MDR1)
      polymorphisms and the risk of developing hepatocellular carcinoma (HCC) is
      currently under debate, and evidence from various epidemiological studies has
      yielded controversial results. To derive a more precise estimation of the
      association between MDR1 polymorphisms and HCC risk, the present meta-analysis
      was performed. A total of 8 studies containing 11 cohorts with 4407 cases and
      4436 controls were included by systematic literature search of EMBASE, PubMed,
      Web of Science, and CNKI. All polymorphisms were classified as mutant/wild-type
      alleles. In particular, the variation type, functional impact, and protein domain
      location of the polymorphisms were assessed and used as stratified indicators.
      The pooled odds ratio (OR) with 95 % confidence interval (CI) was calculated to
      evaluate the association. Overall, our results suggested that the mutant alleles
      of the MDR1 gene were associated with a significantly increased risk for HCC
      under all genetic models (allelic model: OR = 1.28, 95 % CI = 1.20-1.36, P <
      0.001; dominant model: OR = 1.27, 95 % CI = 1.16-1.38, P < 0.001; recessive
      model: OR = 1.59, 95 % CI = 1.36-1.85, P < 0.001). Furthermore, increased risks
      for HCC were also revealed in stratified analyses by ethnicity, sample size, and
      quality scores of cohorts as well as variation type, functional impact, and
      protein domain location of polymorphisms. In conclusion, the present meta
      analysis suggested that the presence of MDR1 mutant alleles might be a risk
      factor for HCC.

PMID- 25861754
TI  - MicroRNA signatures in total peripheral blood of gallbladder cancer patients.
AB  - MicroRNAs (miRNAs) are small non-coding RNA molecules that function as negative
      regulators of gene expression. Expression analysis of miRNAs can reflect the
      developmental lineage and differentiation state of the tumor. Thus, the miRNA
      profiles could play essential roles in gallbladder cancer (GBC). However, their
      role as novel biomarkers for the diagnosis of GBC is unclear yet. We assessed
      here for the first time whole-genome miRNA expression in peripheral blood samples
      of 40 GBC patients using microRNA microarray. We identified 11 miRNAs, which are
      significantly dysregulated in GBC patients in comparison to 40 healthy controls.
      Among these, the expression of let-7a, miR-21, miR-187, miR-143, miR-202, and miR
      335 are in agreement with those measured by real-time PCR (p < 0.05).
      Furthermore, dysregulated miR-187, miR-143, and miR-202 demonstrate a significant
      correlation with clinicopathologic features (p < 0.05). Our results suggest a
      possible pathological relationship between the differential expression of miRNA
      in peripheral blood and GBC, and these dysregulated miRNAs could be novel tumor
      biomarkers for early detection of GBC.

PMID- 25861755
TI  - Oral administration of Lactobacillus plantarum 299v modulates gene expression in
      the ileum of pigs: prediction of crosstalk between intestinal immune cells and
      sub-mucosal adipocytes.
AB  - To study host-probiotic interactions in parts of the intestine only accessible in
      humans by surgery (jejunum, ileum and colon), pigs were used as model for humans.
      Groups of eight 6-week-old pigs were repeatedly orally administered with 5 *
      10(12) CFU Lactobacillus plantarum 299v (L. plantarum 299v) or PBS, starting with
      a single dose followed by three consecutive daily dosings 10 days later. Gene
      expression was assessed with pooled RNA samples isolated from jejunum, ileum and
      colon scrapings of the eight pigs per group using Affymetrix porcine microarrays.
      Comparison of gene expression profiles recorded from L. plantarum 299v-treated
      pigs with PBS-treated pigs indicated that L. plantarum 299v affected metabolic
      and immunological processes, particularly in the ileum. A higher expression level
      of several B cell-specific transcription factors/regulators was observed,
      suggesting that an influx of B cells from the periphery to the ileum and/or the
      proliferation of progenitor B cells to IgA-committed plasma cells in the Peyer's
      patches of the ileum was stimulated. Genes coding for enzymes that metabolize
      leukotriene B4, 1,25-dihydroxyvitamin D3 and steroids were regulated in the
      ileum. Bioinformatics analysis predicted that these metabolites may play a role
      in the crosstalk between intestinal immune cells and sub-mucosal adipocytes.
      Together with regulation of genes that repress NFKB- and PPARG-mediated
      transcription, this crosstalk may contribute to tempering of inflammatory
      reactions. Furthermore, the enzyme adenosine deaminase, responsible for the
      breakdown of the anti-inflammatory mediator adenosine, was strongly down
      regulated in response to L. plantarum 299v. This suggested that L. plantarum 299v
      regulated production of adenosine by immune cells like regulatory T cells may
      also be a mechanism that tempers inflammation in the ileum, and perhaps also in
      other parts of the pig's body. 

PMID- 25861756
TI  - Junctions in human health and inherited disease.

PMID- 25861757
TI  - Evolutionary trails of plant steroid genes.
AB  - Plant steroids - brassinosteroids (BRs) and their precursors, phytosterols - play
      a major role in plant growth, development, stress tolerance, and have high
      potential for agricultural applications. Currently, this prospect is limited by a
      lack of information about their evolution and expression dynamics (spatial and
      temporal) across plant species. The increasing number of sequenced genomes offers
      an opportunity for evolutionary studies that might help to prioritize functional
      analyses with the aim to improve crop yield and stress tolerance. In this review
      we provide a glimpse of the origin, evolution, and functional conservation of
      phytosterol and BR genes in the green plant lineage using comparative sequence
      and expression analyses of publicly available datasets. 

PMID- 25861758
TI  - Spr 2015.

PMID- 25861759
TI  - SimC7 Is a Novel NAD(P)H-Dependent Ketoreductase Essential for the Antibiotic
      Activity of the DNA Gyrase Inhibitor Simocyclinone.
AB  - Simocyclinone D8 (SD8) is a potent DNA gyrase inhibitor produced by Streptomyces
      antibioticus Tu6040. The simocyclinone (sim) biosynthetic gene cluster has been
      sequenced and a hypothetical biosynthetic pathway has been proposed. The tetraene
      linker in SD8 was suggested to be the product of a modular type I polyketide
      synthase working in trans with two monofunctional enzymes. One of these
      monofunctional enzymes, SimC7, was proposed to supply a dehydratase activity
      missing from two modules of the polyketide synthase. In this study, we report the
      function of SimC7. We isolated the entire ~72-kb sim cluster on a single phage
      artificial chromosome clone and produced simocyclinone heterologously in a
      Streptomyces coelicolor strain engineered for improved antibiotic production.
      Deletion of simC7 resulted in the production of a novel simocyclinone, 7-oxo-SD8,
      which unexpectedly carried a normal tetraene linker but was altered in the
      angucyclinone moiety. We demonstrate that SimC7 is an NAD(P)H-dependent
      ketoreductase that catalyzes the conversion of 7-oxo-SD8 into SD8. 7-oxo-SD8 was
      essentially inactive as a DNA gyrase inhibitor, and the reduction of the keto
      group by SimC7 was shown to be crucial for high-affinity binding to the enzyme.
      Thus, SimC7 is an angucyclinone ketoreductase that is essential for the
      biological activity of simocyclinone. 

PMID- 25861760
TI  - Immunoaffinity enrichment coupled to quantitative mass spectrometry reveals
      ubiquitin-mediated signaling events.
AB  - Ubiquitination is one of the most prevalent posttranslational modifications in
      eukaryotic cells, with functional importance in protein degradation, subcellular
      localization and signal transduction pathways. Immunoaffinity enrichment coupled
      with quantitative mass spectrometry enables the in-depth characterization of
      protein ubiquitination events at the site-specific level. We have applied this
      strategy to investigate cellular response triggered by two distinct type agents:
      small molecule inhibitors of the tumor-associated kinases MEK and PI3K or the pro
      inflammatory cytokine IL-17. Temporal profiling of protein ubiquitination events
      across a series of time points covering the biological response permits
      interrogation of signaling through thousands of quantified proteins, of which
      only a subset display significant and physiologically meaningful regulation.
      Distinctive clusters of residues within proteins can display distinct temporal
      patterns attributable to diverse molecular functions, although the majority of
      differential ubiquitination appears as a coordinated response across the
      modifiable residues present within an individual substrate. In cells treated with
      a combination of MEK and PI3K inhibitors, we found differential ubiquitination of
      MEK within the first hour after treatment and a series of mitochondria proteins
      at later time points. In the IL-17 signaling pathway, ubiquitination events on
      several signaling proteins including HOIL-1 and Tollip were observed. The
      functional relevance of these putative IL-17 mediators was subsequently validated
      by knockdown of HOIL-1, HOIP and TOLIP, each of which decreased IL-17-stimulated
      cytokine production. Together, these data validate proteomic profiling of protein
      ubiquitination as a viable approach for identifying dynamic signaling components
      in response to intracellular and extracellular perturbations. 

PMID- 25861761
TI  - The response of Greek key proteins to changes in connectivity depends on the
      nature of their secondary structure.
AB  - What governs the balance between connectivity and topology in regulating the
      mechanism of protein folding? We use circular permutation to vary the order of
      the helices in the all-alpha Greek key protein FADD (Fas-associated death domain)
      to investigate this question. Unlike all-beta Greek key proteins, where changes
      in the order of secondary structure cause a shift in the folding nucleus, the
      position of the nucleus in FADD is unchanged, even when permutation reduces the
      complexity significantly. We suggest that this is because local helical contacts
      are so dominant that permutation has little effect on the entropic cost of
      forming the folding nucleus whereas, in all-beta Greek key proteins, all
      interactions in the nucleus are long range. Thus, the type of secondary structure
      modulates the sensitivity of proteins to changes in connectivity. 

PMID- 25861762
TI  - Structural Variations and Solvent Structure of r(UGGGGU) Quadruplexes Stabilized
      by Sr(2+) Ions.
AB  - Guanine-rich sequences can, under appropriate conditions, adopt a distinctive,
      four-stranded, helical fold known as a G-quadruplex. Interest in quadruplex folds
      has grown in recent years as evidence of their biological relevance has
      accumulated from both sequence analysis and function-specific assays. The folds
      are unusually stable and their formation appears to require close management to
      maintain cell health; regulatory failure correlates with genomic instability and
      a number of cancer phenotypes. Biologically relevant quadruplex folds are
      anticipated to form transiently in mRNA and in single-stranded, unwound DNA. To
      elucidate factors, including bound solvent, that contribute to the stability of
      RNA quadruplexes, we examine, by X-ray crystallography and small-angle X-ray
      scattering, the structure of a previously reported tetramolecular quadruplex,
      UGGGGU stabilized by Sr(2+) ions. Crystal forms of the octameric assembly formed
      by this sequence exhibit unusually strong diffraction and anomalous signal
      enabling the construction of reliable models to a resolution of 0.88A. The
      solvent structure confirms hydration patterns reported for other nucleic acid
      helical conformations and provides support for the greater stability of RNA
      quadruplexes relative to DNA. Novel features detected in the octameric RNA
      assembly include a new crystal form, evidence of multiple conformations and
      structural variations in the 3' U tetrad, including one that leads to the
      formation of a hydrated internal cavity. 

PMID- 25861763
TI  - Structure of a single-chain Fv bound to the 17 N-terminal residues of huntingtin
      provides insights into pathogenic amyloid formation and suppression.
AB  - Huntington's disease is triggered by misfolding of fragments of mutant forms of
      the huntingtin protein (mHTT) with aberrant polyglutamine expansions. The C4
      single-chain Fv antibody (scFv) binds to the first 17 residues of huntingtin
      [HTT(1-17)] and generates substantial protection against multiple phenotypic
      pathologies in situ and in vivo. We show in this paper that C4 scFv inhibits
      amyloid formation by exon1 fragments of huntingtin in vitro and elucidate the
      structural basis for this inhibition and protection by determining the crystal
      structure of the complex of C4 scFv and HTT(1-17). The peptide binds with
      residues 3-11 forming an amphipathic helix that makes contact with the antibody
      fragment in such a way that the hydrophobic face of this helix is shielded from
      the solvent. Residues 12-17 of the peptide are in an extended conformation and
      interact with the same region of another C4 scFv:HTT(1-17) complex in the
      asymmetric unit, resulting in a beta-sheet interface within a dimeric C4
      scFv:HTT(1-17) complex. The nature of this scFv-peptide complex was further
      explored in solution by high-resolution NMR and physicochemical analysis of
      species in solution. The results provide insights into the manner in which C4
      scFv inhibits the aggregation of HTT, and hence into its therapeutic potential,
      and suggests a structural basis for the initial interactions that underlie the
      formation of disease-associated amyloid fibrils by HTT. 

PMID- 25861765
TI  - Cross-cultural adaptation and validation of the Turkish version of Oxford hip
      score.
AB  - INTRODUCTION: The purpose of this study was to translate the Oxford hip score
      (OHS) into Turkish and to evaluate the psychometric properties by testing the
      internal consistency, reproducibility, construct validity, and responsiveness in
      patients with hip osteoarthritis (OA). PATIENTS AND METHODS: Oxford hip score was
      translated and culturally adapted according to the guidelines in the literature.
      Seventy patients (mean age 61.45 +/- 9.29 years) with hip osteoarthritis
      participated in the study. Patients completed the Turkish Oxford hip score (OHS
      TR), the Short-Form 36 (SF-36), and Western Ontario and McMaster Universities
      Index (WOMAC). Internal consistency was tested using Cronbach's alpha
      coefficient. Patients completed OHS-TR questionnaire twice in 7 days for
      determining the reproducibility. Correlation between the total results of both
      tests was determined by the Pearson correlation coefficient and intraclass
      correlation coefficient (ICC). Validity was assessed by calculating the Pearson
      correlation coefficient between the OHS-TR and WOMAC and SF-36 scores. Floor and
      ceiling effects were analyzed. RESULTS: The internal consistency was high
      (Cronbach's alpha 0.93). The construct validity showed a significant correlation
      between the OHS-TR and WOMAC and related SF-36 domains (p < 0.001). The ICC's
      ranged between 0.80 and 0.99. There was no floor or ceiling effect in total OHS
      TR score. CONCLUSIONS: The OHS-TR questionnaire is valid, reliable, and
      responsive for the Turkish-speaking patients with hip OA.

PMID- 25861764
TI  - Sorafenib treatment in Child-Pugh A and B patients with advanced hepatocellular
      carcinoma: safety, efficacy and prognostic factors.
AB  - BACKGROUND: We aimed to evaluate the safety, efficacy and prognostic impact of
      baseline and early clinical markers in both Child-Pugh A and B patients with
      advanced hepatocellular carcinoma (HCC). METHODS: We prospectively studied 89
      Japanese patients with HCC (Child-Pugh A, n = 59; Child-Pugh B, n = 30) who were
      started with sorafenib between May 2010 and July 2013. RESULTS: Frequency of
      sorafenib-related adverse events was almost similar between Child-Pugh score 5,
      6, and 7 patients. The rate of liver dysfunction, including any grade
      encephalopathy, >= grade 3 ascites, or >= grade 3 bilirubin increased, in Child
      Pugh score >=8 group was significantly higher than that in the other groups. The
      median overall survival of Child-Pugh score 5, 6, 7 and >=8 patients were 14.5,
      11.1, 8.7 and 4.6 months, respectively. Patients in Child-Pugh score 6 had
      significantly longer OS than those in Child-Pugh score 7 (P = 0.049).
      Multivariate analysis identified macrovascular invasion (MVI), alpha-fetoprotein
      (AFP), Child-Pugh score and aspartate aminotransferase (AST) as baseline
      predictors of survival. However, extrahepatic metastasis (EHM) was not a
      significant prognostic factor. In addition, decrease in AFP level and development
      of hand-foot skin reaction within 4 weeks after sorafenib initiation were closely
      associated with favorable survival. CONCLUSION: It is possible that not only
      Child-Pugh score 5 and 6 but also 7 patients are eligible for future clinical
      trials with sorafenib or similar drugs. Various survival predictors identified in
      this study might be considered as stratification factor. Although both MVI and
      EHM is a phenotype of advanced HCC, MVI should be discriminated from EHM because
      of the prognostic impact on survival in sorafenib-treated advanced HCC patients.

PMID- 25861766
TI  - Expression Profile of Carotenoid Cleavage Dioxygenase Genes in Summer Squash
      (Cucurbita pepo L.).
AB  - Carotenoids are important dietary components that can be found in vegetable
      crops. The accumulation of these compounds in fruit and vegetables is altered by
      the activity of carotenoid cleavage dioxygenases (CCDs) enzymes that produce
      their degradation. The aim of this work was to study the possible implication of
      CCD genes in preventing carotenoid storage in the horticultural crop summer
      squash (Cucurbita pepo L.). The relationship between the presence of these
      compounds and gene expression for CCDs was studied in three varieties showing
      different peel and flesh colour. Expression analysis for the CCD genes CpNCED1,
      CpNCED2, CpNCED3, CpNCED9, CpCCD1, CpCCD4a, CpCCD4b and CpCCD8 was carried out on
      different organs and at several fruit developmental stages. The results showed
      that the CpCCD4a and CpCCD4b genes were highly expressed in the variety with
      lowest carotenoid content suggesting a putative role in carotenoid accumulation
      pattern in summer squash fruit. 

PMID- 25861767
TI  - Application of a portable infrared instrument for simultaneous analysis of
      sugars, asparagine and glutamine levels in raw potato tubers.
AB  - The level of reducing sugars and asparagine in raw potatoes is critical for
      potato breeders and the food industry for production of commonly consumed food
      products including potato chips and French fries. Our objective was to evaluate
      the use of a portable infrared instrument for the rapid quantitation of major
      sugars and amino acids in raw potato tubers using single-bounce attenuated total
      reflectance (ATR) and dial path accessories as an alternative to time-consuming
      chromatographic techniques. Samples representing a total of 84 experimental and
      commercial potato varieties harvested in two consecutive growing seasons (2012
      and 2013) were used in this study. Samples had wide ranges of sugars determined
      by HPLC-RID (non-detectable (ND)-7.7 mg glucose, ND-9.4 mg fructose and 0.4-5.4
      mg sucrose per 1 g fresh weight), and asparagine and glutamine levels determined
      by GC-FID (0.7-2.9 mg and 0.3-1.7 mg per 1 g fresh weight). Infrared spectra
      collected from 64 varieties were used to create partial least squares regression
      (PLSR) calibration models that predicted the sugar and amino acid levels in an
      independent set of 16 validation potato varieties. Excellent linear correlations
      between infrared predicted and reference values were obtained. PLSR models had a
      high correlation coefficient of prediction (rPred >0.95) and residual predictive
      deviation (RPD) values ranging between 3.1 and 5.5. Overall, the results
      indicated that the models could be used to simultaneously predict sugars, free
      asparagine and glutamine levels in the raw tubers, significantly benefiting
      potato breeding, certain aspects of crop management, crop production and
      research. 

PMID- 25861768
TI  - Chondrogenesis of Human Adipose-Derived Stem Cells by In Vivo Co-graft with
      Auricular Chondrocytes from Microtia.
AB  - OBJECTIVE: To evaluate the efficiency of chondrogenesis of human adipose-derived
      stem cells (ADSCs) induced by auricular chondrocytes from microtia via
      subcutaneous co-graft in nude mice. METHODS: Human ADSCs and auricular
      chondrocytes were mixed at the ratio of 7:3 and suspended in 0.2 ml of Pluronic F
      127 (5.0 * 10(7) cells/ml), and injected into Balb/c nude mice as the
      experimental group (Exp group). The same quantity of auricular chondrocytes
      (Ctr.1 group) or ADSCs (Ctr.2 group) in 0.2 ml of Pluronic F-127 was set as
      positive and negative control groups. The mixture of auricular chondrocytes (1.5
      * 10(7) cells/ml) in 0.2 ml of Pluronic F-127 was set as the low concentration of
      chondrocyte control group (Ctr.3). At 8 weeks after grafting, the newly generated
      tissue pellets were isolated for morphological examination, haematoxylin and
      eosin staining, toluidine blue staining and safranin O staining of
      glycosaminoglycan (GAG), Masson's trichrome staining and immunohistochemical
      staining of type II collagen, and Verhoeff-iron-hematoxylin staining of elastic
      fibers. GAG content was determined by Alcian blue colorimetric method, and mRNA
      expression of type II collagen and aggrecan were examined by real-time PCR.
      RESULTS: Cartilage-like tissue with a white translucent appearance and good
      elasticity was generated in the Exp and Ctr.1 groups. The tissue pellets in the
      Ctr.2 and Ctr.3 groups were much smaller than those in the Ctr.1 group. The
      mature cartilage lacunas could be observed in the Exp and Ctr.1 groups, while
      were rarely seen in the Ctr.3 group and not observed in the Ctr.2 group. The
      expression of cartilage-specific extracellular matrix such as type II collagen,
      GAG content, aggrecan, and elastic fibers in the Exp group was similar to that in
      the Ctr.1 group, whereas the expression of these extracellular matrix substances
      was significantly lower in the Ctr.2 and Ctr.3 groups (both P < 0.01).
      CONCLUSION: Auricular chondrocytes from microtia can efficiently promote the
      chondrogenic differentiation and chondrogenesis of ADSCs by co-grafting in vivo.
      NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence
      to each submission to which Evidence-Based Medicine rankings are applicable. This
      excludes Review Articles, Book Reviews, and manuscripts that concern Basic
      Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full
      description of these Evidence-Based Medicine ratings, please refer to the Table
      of Contents or the online Instructions to Authors http://www.springer.com/00266 .

PMID- 25861769
TI  - Visuo-constructional functions in patients with mild cognitive impairment,
      Alzheimer's disease, and Parkinson's disease.
AB  - BACKGROUND: Several recently proposed criteria for assessing cognitive disorder
      require measuring the cognitive domain of visuo-constructional function. The aims
      of the present study were to develop a new test (Vienna Visuo-constructional Test
      VVT) measuring visuo-constructional functions and to determine the reliability
      and validity of the VVT in patients with mild cognitive impairment (MCI),
      Parkinson's disease (PD), and Alzheimer's disease (AD). We further examined age
      and sex effects and the psychometric quality of the VVT. METHODS: The study
      included 76 healthy controls and 103 patients who were referred to the Department
      of Neurology, Medical University of Vienna for neurocognitive assessment. An
      administering and scoring system for the VVT was developed. RESULTS: Internal
      consistency (Cronbach's alpha) was found to range from 0.82 for the healthy
      control group to 0.93 for the total patient group. There was no sex effect, but
      age had a negative effect on VVT performance. The VVT successfully differentiated
      healthy controls from MCI patients, AD patients, and PD patients, respectively.
      CONCLUSION: The VVT shows satisfactory validity and reliability and can be
      administered easily in clinical practice. It constitutes a new measure that can
      successfully be used to identify visuo-constructional problems in patients with
      cognitive dysfunction.

PMID- 25861770
TI  - MetaMirClust: Discovery and Exploration of Evolutionarily Conserved miRNA
      Clusters.
AB  - Recent emerging studies suggest that a substantial fraction of microRNA (miRNA)
      genes is likely to form clusters in terms of evolutionary conservation and
      biological implications, posing a significant challenge for the research
      community and shifting the bottleneck of scientific discovery from miRNA
      singletons to miRNA clusters. In addition, the advance in molecular sequencing
      technique such as next-generation sequencing (NGS) has facilitated researchers to
      comprehensively characterize miRNAs with low abundance on genome-wide scale in
      multiple species. Taken together, a large scale, cross-species survey of grouped
      miRNAs based on genomic location would be valuable for investigating their
      biological functions and regulations in an evolutionary perspective. In the
      present chapter, we describe the application of effective and efficient
      bioinformatics tools on the identification of clustered miRNAs and illustrate how
      to use the recently developed Web-based database, MetaMirClust
      (http://fgfr.ibms.sinic.aedu.tw/MetaMirClust) to discover evolutionarily
      conserved pattern of miRNA clusters across metazoans.

PMID- 25861771
TI  - Historical background of itch.
AB  - Itch as a disease, and especially as a symptom, was the object of medical and
      scientific curiosity for centuries. The reluctance of historians to focus on the
      history of itch relates to its nature as a subjective symptom. After all, how can
      historians have known what itch really felt like in previous centuries? Since the
      establishment of dermatology as an independent discipline of medicine in the
      middle of the nineteenth century, itch has become a subject of investigation in
      its own right. This chapter summarises research we conducted on the medical
      history of itch in ancient medicine and up through the twentieth century. 

PMID- 25861772
TI  - Pruritus epidemiology and quality of life.
AB  - The burden of chronic pruritus is increasingly recognized as significant
      worldwide. As wet-laboratory researchers investigate the pathophysiology of
      chronic pruritus, epidemiologists and health services researchers are quantifying
      the impact of pruritus by incidence, prevalence, and quality of life measures.
      Outcomes researchers are also investigating factors that may predict chronic
      pruritus incidence and severity. Such efforts will direct resources for research,
      public health intervention, and clinical care. 

PMID- 25861773
TI  - Neurophysiology and itch pathways.
AB  - As we all can easily differentiate the sensations of itch and pain, the most
      straightforward neurophysiologic concept would consist of two specific pathways
      that independently encode itch and pain. Indeed, a neuronal pathway for histamine
      induced itch in the peripheral and central nervous system has been described in
      animals and humans, and recently several non-histaminergic pathways for itch have
      been discovered in rodents that support a dichotomous concept differentiated into
      a pain and an itch pathway, with both pathways being composed of different
      "flavors." Numerous markers and mediators have been found that are linked to itch
      processing pathways. Thus, the delineation of neuronal pathways for itch from
      pain pathways seemingly proves that all sensory aspects of itch are based on an
      itch-specific neuronal pathway. However, such a concept is incomplete as itch can
      also be induced by the activation of the pain pathway in particular when the
      stimulus is applied in a highly localized spatial pattern. These opposite views
      reflect the old dispute between specificity and pattern theories of itch. Rather
      than only being of theoretic interest, this conceptual problem has key
      implication for the strategy to treat chronic itch as key therapeutic targets
      would be either itch-specific pathways or unspecific nociceptive pathways. 

PMID- 25861774
TI  - Neuroimaging of itch as a tool of assessment of chronic itch and its management.
AB  - Chronic itch is a multidimensional physical state strongly associated with
      emotional and cognitive aspects of suffering that causes the urge to scratch.
      Pathophysiology, psychological stress, and social milieu can influence itch.
      Here, we review brain neuroimaging research in humans that detects functional and
      anatomic changes in health and disease states. New data are emerging that are
      shaping our understanding of itch mechanisms and scratching-the behavioral
      response as well as the effect of treatments and brain dynamics during itch.
      Future developments will continue to expand our knowledge of itch mechanisms,
      allowing translation to clinical assessment and novel therapies focused on the
      brain, the final relay of itch transmission. 

PMID- 25861775
TI  - The role of the Mrgpr receptor family in itch.
AB  - Itch is a complex sensory modality that can be evoked by an extremely diverse set
      of stimuli and has multiple components of disease etiology. Thus, determining the
      basic molecular and cellular players is essential before we can tackle the more
      complex aspects of itch. The identification of novel itch receptors has been
      extremely fruitful and has uncovered novel signaling pathways and pruritogens.
      Mrgprs encode a family of G protein-coupled receptors, many of which are
      expressed specifically in sensory nerves and function as itch receptors in
      mediating histamine-independent itch. In this chapter, we will review the
      discovery of the receptor family, their specific expression, their roles as itch
      receptors, and the itch-inducing agonists. Furthermore, we will summarize the
      results indicating that Mrgpr-expressing sensory neurons are itch-sensing
      neurons. In the end we will discuss the role of Mrgprs and Mrgpr-positive neurons
      in chronic itch. 

PMID- 25861776
TI  - Transient receptor potential channels and itch: how deep should we scratch?
AB  - Over the past 30 years, transient receptor potential (TRP) channels have evolved
      from a somewhat obscure observation on how fruit flies detect light to become the
      center of drug discovery efforts, triggering a heated debate about their
      potential as targets for therapeutic applications in humans. In this review, we
      describe our current understanding of the diverse mechanism of action of TRP
      channels in the itch pathway from the skin to the brain with focus on the
      peripheral detection of stimuli that elicit the desire to scratch and spinal itch
      processing and sensitization. We predict that the compelling basic research
      findings on TRP channels and pruritus will be translated into the development of
      novel, clinically useful itch medications. 

PMID- 25861777
TI  - Itch control by Toll-like receptors.
AB  - Toll-like receptors (TLRs) are cellular sensors designed to recognize molecular
      danger signals associated with exogenous or endogenous threats. Their activation
      leads to initiation of the host's immune responses in order to remove or contain
      the danger. However, one of the most effective methods of defense against
      invading pathogens and parasites is itch. The perception of itch elicits the
      rapid defensive action to scratch, which can remove the offending pathogen or
      parasite before infection can occur. Recent findings show that TLRs such as TLR3,
      TLR4, and TLR7 are expressed in a subset of pruriceptive/nociceptive neurons in
      the dorsal root and trigeminal ganglion providing a direct link between TLR
      activation and itch. Activation of neuronal TLRs can initiate itch sensation by
      coupling with ion channels. Furthermore, TLRs are expressed in skin cells and
      glial cells in the spinal cord to regulate inflammation and neuroinflammation in
      chronic itch. Thus, identification of the role of TLRs in neurons, skin cells,
      and glial cells may provide new targets for the treatment of chronic itch, a
      common clinical problem associated with skin diseases, systemic diseases, and
      metabolic disorders, for which current treatments are far from sufficient. 

PMID- 25861779
TI  - Role of cytokines and chemokines in itch.
AB  - Cytokines classically are secreted "messenger" proteins that modulate cellular
      function of immune cells. Chemokines attract immune cells to the site where they
      exert various functions in inflammation, autoimmunity or cancer. Increasing
      evidence is emerging that cytokines or chemokines can act as "neuro-modulators"
      by activating high-affinity receptors on peripheral or central neurons, microglia
      cells or Schwann cells. Very recently, cytokines have been shown to act as
      pruritogens in rodents and humans, while a role of chemokines in itch has thus
      far been only demonstrated in mice. Upon stimulation, cytokines are released by
      skin or immune cells and form a "bridge of communication" between the immune and
      nervous system. For some cytokines such as IL-31 and TSLP, the evidence for this
      role is strong in rodents. For cytokines such as IL-4, there is some convincing
      evidence, while for cytokines such as oncostatin M, IL-2, IL-6, IL-8 and IL-13,
      direct evidence is currently limited. Current clinical trials support the idea
      that cytokines and chemokines and their receptors or signalling pathways are
      promising targets for the future therapy of certain subtypes of itch. 

PMID- 25861778
TI  - Transmission of pruriceptive signals.
AB  - In this chapter we discuss the many recent discoveries of the mechanisms by which
      itch is transmitted: the neurotransmitters and the responses they trigger, the
      mechanisms by which specific neuronal targets are activated, and the specificity
      of the pathways. Current data reveal that DRG neurons and spinal cord cells use a
      remarkably selective set of transmitters to convey pruritic information from the
      periphery to the brain: glutamate and Nppb are released from primary itch-sensory
      cells; these molecules activate secondary spinal cord pruriceptive-specific
      neurons, which in turn utilize Grp to activate tertiary pruriceptive-selective
      neurons. Intersecting this basic linear excitatory pathway, inhibitory input from
      dynorphin and neurons that express the somatostatin receptor modify itch
      sensation. Cumulatively, these studies paint an elegantly simple picture of how
      itch signals are transformed and integrated in the spinal cord and open new
      avenues for research efforts aimed at understanding and better treating itch. 

PMID- 25861780
TI  - Interactions between keratinocytes and somatosensory neurons in itch.
AB  - Keratinocytes are epithelial cells that make up the stratified epidermis of the
      skin. Recent studies suggest that keratinocytes promote chronic itch. Changes in
      skin morphology that accompany a variety of chronic itch disorders and the
      multitude of inflammatory mediators secreted by keratinocytes that target both
      sensory neurons and immune cells highlight the importance of investigating the
      connection between keratinocytes and chronic itch. This chapter addresses some of
      the most recent data and models for the role keratinocytes play in the
      development and maintenance of chronic itch. 

PMID- 25861781
TI  - Itch and its inhibition by counter stimuli.
AB  - Recent studies have made significant progress in the knowledge of how itch
      sensation is processed, especially the molecular identity of neurons involved in
      itch signaling, both in the dorsal root ganglion and spinal cord. Despite these
      advances, the organization of these neurons in dorsal spinal cord circuits and
      how they interact with other somatosensory modalities, such as pain or
      temperature, remain relatively unexplored. Recent work from our lab and others
      has begun to shed light on these questions and will be the focus of this chapter.
      Here we describe the discovery of B5-I neurons, a population of inhibitory
      interneurons that function to inhibit itch, and review the evidence that these
      neurons mediate the inhibition of itch by counter stimuli. These studies are
      helping to solve the long-standing question of why itch makes us scratch. 

PMID- 25861782
TI  - Noradrenergic modulation of itch transmission in the spinal cord.
AB  - Inhibition of both itching and scratching is important in the treatment of
      chronic pruritic diseases, because itching has a negative impact on quality of
      life and vigorous scratching worsens skin conditions. Pharmacological modulation
      of itch transmission in the dorsal horn is an effective way to inhibit both
      itching and scratching in pruritic diseases. Pruriceptive transmission in the
      spinal dorsal horn undergoes inhibitory modulation by the descending
      noradrenergic system. The noradrenergic inhibition is mediated by excitatory
      alpha1-adrenoceptors located on inhibitory interneurons and inhibitory alpha2
      adrenoceptors located on central terminals of primary sensory neurons. The
      descending noradrenergic system and alpha-adrenoceptors in the dorsal horn are
      potential targets for antipruritic drugs.

PMID- 25861784
TI  - NK-1 Antagonists and Itch.
AB  - Substance P (SP) is an important mediator of pro-inflammatory mechanisms in the
      skin. It targets multiple cells such as keratinocytes, mast cells, and
      fibroblasts which are involved in the cutaneous generation of pruritus. This
      suggests that SP is an interesting target for therapy. In fact, in recent case
      reports and case series, SP antagonists demonstrated a significant antipruritic
      effect in acute and chronic pruritus such as drug-induced pruritus,
      paraneoplastic pruritus, prurigo nodularis, cutaneous T-cell lymphoma, and
      brachioradial pruritus. 

PMID- 25861783
TI  - Protease-activated receptors and itch.
AB  - Protease-activated receptors (PARs) have been implicated in a variety of
      physiological functions, as well as somatosensation and particularly itch and
      pain. Considerable attention has focused on PARs following the finding they are
      upregulated in the skin of atopic dermatitis patients. The present review focuses
      on recent studies showing that PARs are critically involved in itch and
      sensitization of itch. PARs are expressed by diverse cell types including primary
      sensory neurons, keratinocytes, and immune cells and are activated by proteases
      that expose a tethered ligand. Endogenous proteases are also released from
      diverse cell types including keratinocytes and immune cells. Exogenous proteases
      released from certain plants and insects contacting the skin can also induce
      itch. Increased levels of proteases in the skin contribute to inflammation that
      is often accompanied by chronic itch which is not predominantly mediated by
      histamine. The neural pathway signaling itch induced by activation of PARs is
      distinct from that mediating histamine-induced itch. In addition, there is
      evidence that PARs play an important role in sensitization of itch signaling
      under conditions of chronic itch. These recent findings suggest that PARs and
      other molecules involved in the itch-signaling pathway are good targets to
      develop novel treatments for most types of chronic itch that are poorly treated
      with antihistamines. 

PMID- 25861785
TI  - Antihistamines and itch.
AB  - Histamine is one of the best-characterized pruritogens in humans. It is known to
      play a role in pruritus associated with urticaria as well as ocular and nasal
      allergic reactions. Histamine mediates its effect via four receptors.
      Antihistamines that block the activation of the histamine H1receptor, H1R, have
      been shown to be effective therapeutics for the treatment of pruritus associated
      with urticaria, allergic rhinitis, and allergic conjunctivitis. However, their
      efficacy in other pruritic diseases such as atopic dermatitis and psoriasis is
      limited. The other histamine receptors may also play a role in pruritus, with the
      exception of the histamine H2receptor, H2R. Preclinical evidence indicates that
      local antagonism of the histamine H3receptor, H3R, can induce scratching perhaps
      via blocking inhibitory neuronal signals. The histamine H4receptor, H4R, has
      received a significant amount of attention as to its role in mediating pruritic
      signals. Indeed, it has now been shown that a selective H4R antagonist can
      inhibit histamine-induced itch in humans. This clinical result, in conjunction
      with efficacy in various preclinical pruritus models, points to the therapeutic
      potential of H4R antagonists for the treatment of pruritus not controlled by
      antihistamines that target the H1R.

PMID- 25861786
TI  - Targeting Itch with Ligands Selective for kappa Opioid Receptors.
AB  - Several chemically diverse pruritogens, including bombesin, compound 48/80,
      norbinaltorphimine, and 5'-GNTI, cause rodents to scratch excessively in a
      stable, uniform manner and consequently provide convenient animal models of itch
      against which potential antipruritics may be evaluated, structure-activity
      relationships established, and the nature of spontaneous, repetitive behavior
      itself analyzed. Decreasing the number of scratching bouts in these apparently
      simple models has been the requisite first step in the progress of kappa opioid
      agonists such as nalbuphine, asimadoline, and CR845 toward clinical testing as
      antipruritics. Nalfurafine is the prime example of a kappa agonist spanning the
      developmental divide between scratching mice models and commercialization within
      10 years. Patients undergoing hemodialysis and suffering from the itching
      associated with uremic pruritus, and potentially those inflicted with atopic
      dermatitis, are the beneficiaries. 

PMID- 25861788
TI  - Current topical and systemic therapies for itch.
AB  - Itch is a common distressing symptom which may be caused by multifactorial
      aetiologies including inflammatory skin diseases, systemic diseases, neuropathic
      conditions and psychogenic disorders. Itch is a term used synonymously with
      pruritus and is defined as acute if it lasts less than 6 weeks or chronic if it
      persists for more than 6 weeks. It can have the same impact on the quality of
      life as chronic pain and shares many of the same pathophysiological pathways.
      Depending on the aetiology of the itch, different pathogenic mechanisms have been
      postulated with a number of mediators identified. These include histamine,
      leukotrienes, proteases, neuropeptides, cytokines and opioids, which may activate
      peripheral itch-mediating C-fibres via receptors on the nerve terminals and
      central neuronal pathways. Therefore, there is no single universally effective
      anti-itch treatment available. First-line treatments for itch include topical
      therapies, such as emollients, mild cleansers (low pH), topical anaesthetics,
      steroids, calcineurin inhibitors and coolants (menthol). Treatment with systemic
      therapies can vary according to the aetiology of the chronic itch. Non-sedating
      antihistamines are helpful in conditions such as urticaria where the itch is
      primarily histamine mediated. Although the itch of eczema is not mediated by
      histamine, sedating antihistamines at night are helpful to break the itch-scratch
      cycle. Chronic itch may also be treated with other systemic therapies, such as
      anticonvulsants, antidepressants as well as mu-opioid antagonists, kappa-opioid
      agonists and phototherapy, depending on the cause of the itch. This article
      summarises the topical and systemic therapies available with our current
      understanding of the pathophysiology of itch. 

PMID- 25861789
TI  - Atopic itch in dogs: pharmacology and modeling.
AB  - Itch is the most common clinical problem seen in dogs with skin diseases.
      Although an etiological classification of canine pruritus does not yet exist,
      most causes would likely fall into the IFSI class I (dermatological) itch. One of
      the most common causes of canine itch is that associated with atopic dermatitis,
      and there is randomized controlled trial grade evidence of the efficacy of
      several antipruritic interventions. At this time, the mainstay of treatment of
      canine atopic itch relies principally on the use of topical and/or oral
      glucocorticoids and oral cyclosporine. Type 1 receptor antihistamines are
      notorious in their inconsistency in reducing pruritus in atopic dogs. A new Janus
      kinase (JAK)-1 inhibitor has recently been approved for treatment of allergic
      itch in dogs, and its onset of efficacy is remarkably fast. Modeling itch in dogs
      can be achieved by allergen sensitization (fleas, house dust mites), and
      challenges that elicit pruritic manifestation can be used for mechanistic studies
      as well as for testing of novel anti-itch modalities. 

PMID- 25861787
TI  - Neuraxial opioid-induced itch and its pharmacological antagonism.
AB  - Given its profound analgesic nature, neuraxial opioids are frequently used for
      pain management. Unfortunately, the high incident rate of itch/pruritus after
      spinal administration of opioid analgesics reported in postoperative and
      obstetric patients greatly diminishes patient satisfaction and thus the value of
      the analgesics. Many endeavors to solve the mystery behind neuraxial opioid
      induced itch had not been successful, as the pharmacological antagonism other
      than the blockade of mu opioid receptors remains elusive. Nevertheless, as the
      characteristics of all opioid receptor subtypes have become more understood, more
      studies have shed light on the potential effective treatments. This review
      discusses the mechanisms underlying neuraxial opioid-induced itch and compares
      pharmacological evidence in nonhuman primates with clinical findings across
      diverse drugs. Both nonhuman primate and human studies corroborate that mixed
      mu/kappa opioid partial agonists seem to be the most effective drugs in
      ameliorating neuraxial opioid-induced itch while retaining neuraxial opioid
      induced analgesia. 

PMID- 25861790
TI  - The Determinants of young Adult Social well-being and Health (DASH) study:
      diversity, psychosocial determinants and health.
AB  - PURPOSE: The Determinants of young Adult Social well-being and Health
      longitudinal study draws on life-course models to understand ethnic differences
      in health. A key hypothesis relates to the role of psychosocial factors in
      nurturing the health and well-being of ethnic minorities growing up in the UK. We
      report the effects of culturally patterned exposures in childhood. METHODS: In
      2002/2003, 6643 11-13 year olds in London, ~80 % ethnic minorities, participated
      in the baseline survey. In 2005/2006, 4782 were followed-up. In 2012-2014, 665
      took part in a pilot follow-up aged 21-23 years, including 42 qualitative
      interviews. Measures of socioeconomic and psychosocial factors and health were
      collected. RESULTS: Ethnic minority adolescents reported better mental health
      than White British, despite more adversity (e.g. economic disadvantage, racism).
      It is unclear what explains this resilience but findings support a role for
      cultural factors. Racism was an adverse influence on mental health, while family
      care and connectedness, religious involvement and ethnic diversity of friendships
      were protective. While mental health resilience was a feature throughout
      adolescence, a less positive picture emerged for cardio-respiratory health. Both,
      mental health and cultural factors played a role. These patterns largely endured
      in early 20s with family support reducing stressful transitions to adulthood.
      Education levels, however, signal potential for socio-economic parity across
      ethnic groups.

PMID- 25861791
TI  - CORR Insights((r)): Kaplan-Meier Survival Analysis Overestimates the Risk of
      Revision Arthroplasty: A Meta-analysis.

PMID- 25861793
TI  - Photographic art in exam rooms may reduce white coat hypertension.
AB  - INTRODUCTION: Blood pressure (BP) elevation in medical office settings in
      patients who are normotensive in nonmedical settings is an effect known as 'white
      coat hypertension'. This phenomenon is thought to be due to situational anxiety
      caused by the experience of visiting a doctor and the anxiety-inducing nature of
      the medical office. Our study was designed to determine if carefully selected
      photographic art could counter the anxiety that causes white coat hypertension
      and lead to lower BP recordings in some patients. METHODS: 117 adults, non
      pregnant patients from the Louisiana State University Health Sciences Center
      Family Medicine Resident Clinic participated in this study. After the triage
      nurse measured the BP, the patients were randomly placed in either an exam room
      with standard medical posters (control room) or in an exam room with photographic
      art (photo room). The BP was measured in the exam room. After the medical visit,
      the patients switched rooms and the BP was measured a third time. The patients
      were asked to fill out a questionnaire to identify room preference. RESULTS: On
      average, the BP obtained in the control rooms was higher than that obtained in
      the photo rooms. There was a statistically significant difference between the
      mean arterial pressure, systolic BP and diastolic BP between the control room and
      the photo room. CONCLUSIONS: Landscape photographic art may have the beneficial
      effect of reducing BP in medical office examination rooms.

PMID- 25861792
TI  - Apolipoprotein A-I mimetic peptide 4F blocks sphingomyelinase-induced LDL
      aggregation.
AB  - Lipolytic modification of LDL particles by SMase generates LDL aggregates with a
      strong affinity for human arterial proteoglycans and may so enhance LDL retention
      in the arterial wall. Here, we evaluated the effects of apoA-I mimetic peptide 4F
      on structural and functional properties of the SMase-modified LDL particles. LDL
      particles with and without 4F were incubated with SMase, after which their
      aggregation, structure, and proteoglycan binding were analyzed. At a molar ratio
      of L-4F to apoB-100 of 2.5 to 20:1, 4F dose-dependently inhibited SMase-induced
      LDL aggregation. At a molar ratio of 20:1, SMase-induced aggregation was fully
      blocked. Binding of 4F to LDL particles inhibited SMase-induced hydrolysis of LDL
      by 10% and prevented SMase-induced LDL aggregation. In addition, the binding of
      the SMase-modified LDL particles to human aortic proteoglycans was dose
      dependently inhibited by pretreating LDL with 4F. The 4F stabilized apoB-100
      conformation and inhibited SMase-induced conformational changes of apoB-100.
      Molecular dynamic simulations showed that upon binding to protein-free LDL
      surface, 4F locally alters membrane order and fluidity and induces structural
      changes to the lipid layer. Collectively, 4F stabilizes LDL particles by
      preventing the SMase-induced conformational changes in apoB-100 and so blocks
      SMase-induced LDL aggregation and the resulting increase in LDL retention. 

PMID- 25861794
TI  - Youth social withdrawal behavior (hikikomori): A systematic review of qualitative
      and quantitative studies.
AB  - OBJECTIVE: Acute and/or severe social withdrawal behavior among youth was seen as
      a culture-bound psychiatric syndrome in Japan, but more youth social withdrawal
      cases in different countries have been discovered recently. However, due to the
      lack of a formal definition and diagnostic tool for youth social withdrawal,
      cross-cultural observational and intervention studies are limited. We aimed to
      consolidate existing knowledge in order to understand youth social withdrawal
      from diverse perspectives and suggest different interventions for different
      trajectories of youth social withdrawal. METHOD: This review examined the current
      available scientific information on youth social withdrawal in the academic
      databases: ProQuest, ScienceDirect, Web of Science and PubMed. We included
      quantitative and qualitative studies of socially withdrawn youths published in
      English and academic peer-reviewed journals. RESULTS: We synthesized the
      information into the following categories: (1) definitions of youth social
      withdrawal, (2) developmental theories, (3) factors associated with youth social
      withdrawal and (4) interventions for socially withdrawn youths. Accordingly,
      there are diverse and controversial definitions for youth social withdrawal.
      Studies of youth social withdrawal are based on models that lead to quite
      different conclusions. Researchers with an attachment perspective view youth
      social withdrawal as a negative phenomenon, whereas those who adopt Erikson's
      developmental theory view it more positively as a process of seeking self
      knowledge. Different interventions for socially withdrawn youths have been
      developed, mainly in Japan, but evidence-based practice is almost non-existent.
      CONCLUSION: We propose a theoretical framework that views youth social withdrawal
      as resulting from the interplay between psychological, social and behavioral
      factors. Future validation of the framework will help drive forward advances in
      theory and interventions for youth social withdrawal as an emerging issue in
      developed countries.

PMID- 25861795
TI  - Islamic State executes 10 doctors for refusing to treat its wounded fighters.

PMID- 25861796
TI  - Is early induction or expectant management more beneficial in women with late
      preterm pre-eclampsia?

PMID- 25861799
TI  - Phosphodiesterases in the rat ovary: effect of cAMP in primordial follicles.
AB  - Phosphodiesterases (PDEs) are important regulators of the intracellular cAMP
      concentration, which is a central second messenger that affects a multitude of
      intracellular functions. In the ovaries, cAMP exerts diverse functions, including
      regulation of ovulation and it has been suggested that augmented cAMP levels
      stimulate primordial follicle growth. The present study examined the gene
      expression, enzyme activity and immunolocalization of the different cAMP
      hydrolysing PDEs families in the rat ovary. Further, the effect of PDE4
      inhibition on primordial follicle activation in cultured neonatal rat ovaries was
      also evaluated. We found varied expression of all eight families in the ovary
      with Pde7b and Pde8a having the highest expression each accounting for more than
      20% of the total PDE mRNA. PDE4 accounted for 15-26% of the total PDE activity.
      Immunoreactive PDE11A was found in the oocytes and PDE2A in the corpora lutea.
      Incubating neonatal rat ovaries with PDE4 inhibitors did not increase primordial
      follicle activation or change the expression of the developing follicle markers
      Gdf9, Amh, Inha, the proliferation marker Mki67 or the primordial follicle marker
      Tmeff2. In addition, the cAMP analogue 8-bromo-cAMP did not increase AKT1 or
      FOXO3A phosphorylation associated with follicle activation or increase the
      expression of Kitlg known to be associated with follicle differentiation but did
      increase the Tmeff2, Mki67 and Inha expression in a dose-dependent manner. In
      conclusion, this study shows that both Pde7b and Pde8a are highly expressed in
      the rodent ovary and that PDE4 inhibition does not cause an increase in
      primordial follicle activation. 

PMID- 25861797
TI  - Mitochondrial dynamism and heart disease: changing shape and shaping change.
AB  - Mitochondria of adult cardiomyocytes appear hypo-dynamic, lacking interconnected
      reticular networks and the continual fission and fusion observed in many other
      cell types. Nevertheless, proteins essential to mitochondrial network remodeling
      are abundant in adult hearts. Recent findings from cardiac-specific ablation of
      mitochondrial fission and fusion protein genes have revealed unexpected roles for
      mitochondrial dynamics factors in mitophagic mitochondrial quality control. This
      overview examines the clinical and experimental evidence for and against a
      meaningful role for the mitochondrial dynamism-quality control interactome in
      normal and diseased hearts. Newly discovered functions of mitochondrial dynamics
      factors in maintaining optimal cardiac mitochondrial fitness suggest that deep
      interrogation of clinical cardiomyopathy is likely to reveal genetic variants
      that cause or modify cardiac disease through their effects on mitochondrial
      fission, fusion, and mitophagy. 

PMID- 25861798
TI  - Human chorionic gonadotropin increases serum progesterone, number of corpora
      lutea and angiogenic factors in pregnant sheep.
AB  - Early gestation is a critical period when implantation and placental
      vascularization are established, processes influenced by progesterone (P4).
      Although human chorionic gonadotropin (hCG) is not endogenously synthesized by
      livestock, it binds the LH receptor, stimulating P4 synthesis. We hypothesized
      treating pregnant ewes with hCG would increase serum P4, number of corpora lutea
      (CLs) and concepti, augment steroidogenic enzymes, and increase membrane P4
      receptors (PAQRs) and angiogenic factors in reproductive tissues. The objective
      was to determine molecular alterations induced by hCG in pregnant sheep that may
      promote pregnancy. Ewes received either 600 IU of hCG or saline i.m. on day 4
      post mating. Blood samples were collected daily from day 0 until tissue
      collection for serum P4 analysis. Reproductive tissues were collected on either
      day 13 or 25 of gestation and analyzed for PAQRs, CXCR4, proangiogenic factors
      and steroidogenic enzymes. Ewes receiving hCG had more CL and greater serum P4,
      which remained elevated. On day 25, StAR protein production decreased in CL from
      hCG-treated ewes while HSD3B1 was unchanged; further, expression of CXCR4
      significantly increased and KDR tended to increase. PAQR7 and CXCR4 protein was
      increased in caruncle tissue from hCG-treated ewes. Maternal hCG exposure
      influenced fetal extraembryonic tissues, as VEGFA, VEGFB, FLT1, and ANGPT1
      expression increased. Our results indicate hCG increases serum P4 due to
      augmented CL number per ewe. hCG treatment resulted in greater PAQR7 and CXCR4 in
      maternal endometrium and promoted expression of proangiogenic factors in fetal
      extraembryonic membranes. Supplementing livestock with hCG may boost P4 levels
      and improve reproductive efficiency. 

PMID- 25861800
TI  - Low-Level Fluoride Exposure Increases Insulin Sensitivity in Experimental
      Diabetes.
AB  - The effect of chronic fluoride (F) exposure from the drinking water on parameters
      related to glucose homeostasis was investigated. Wistar rats were randomly
      distributed into 2 groups (diabetic [D] and nondiabetic [ND]; n = 54 each). In D,
      diabetes was induced with streptozotocin. Each group was further divided into 3
      subgroups (0, 10, or 50 mgF/L in drinking water). After 22 days of treatment,
      plasma and liver samples were collected. No alterations in glycemia, insulinemia,
      K(ITT), and HOMA2-IR (homeostasis model assessment 2 of insulin resistance) were
      seen for ND. F-exposure of D rats led to significantly lower insulinemia, without
      alterations in glycemia (increased %S). Proteomic analysis detected 19, 39, and
      16 proteins differentially expressed for the comparisons D0 vs. D10, D0 vs. D50,
      and D10 vs. D50, respectively. Gene Ontology with the most significant terms in
      the comparisons D0 vs. D10, D0 vs. D50, and D50 vs. D10 were organic acid
      metabolic process and carboxylic acid metabolic process, organic acid metabolic
      process, and cellular ketone metabolic process. Analysis of subnetworks revealed
      that proteins with fold changes interacted with GLUT4 in comparison D0 vs. D10.
      Among these proteins, ERj3p was present in D10. Upregulation of this protein in
      the presence of F might help to explain the higher %S found in these animals.
      These data suggest that fluoride might enhance glucose homeostasis in diabetes
      and identify specific biological mechanisms that merit future studies.

PMID- 25861801
TI  - Epithelial Cell Apoptosis in Recurrent Aphthous Ulcers.
AB  - A recurrent aphthous ulcer (RAU) is a common inflammatory ulcerative lesion
      affecting oral mucosa. We studied the eventual apoptosis of epithelial cells from
      the point of view of ulcer and inflammation. RAU lesions and healthy mucosa
      samples were immunostained for caspase-3 and high-mobility group box 1 (HMGB1).
      DNA nicks were identified using TUNEL staining. We studied the effects of tumor
      necrosis factor alpha (TNFalpha) and interferon gamma (IFNgamma) on the toll-like
      receptor 2 and 4 (TLR2 and TLR4) expression of human oral SCC-25 keratinocytes.
      We also studied the effects of self-DNA, all-thiol-HMGB1, and disulfide-HMGB1 on
      epithelial cells, with or without IFNgamma. At the edge of RAU lesions, all
      epithelial cell layers were caspase-3(+), TUNEL(+), and HMGB-1(+) and had widened
      intercellular spaces. In contrast, healthy epithelial cells were negative for
      caspase-3 and TUNEL staining. HMGB1 was seen in only the basal cell layers, and
      the cells retained close cell-to-cell contacts. Self-DNA increased TNF-alpha mRNA
      (P = 0.02) in SCC-25 cells. Both TNFalpha and IFNgamma (P = 0.01) increased TLR2.
      Upon TNFalpha stimulation, SCC-25 cells lost their nuclear HMGB1 staining. HMGB1
      did not increase IL-8, IL-6, or TNF-alpha mRNA in SCC-25 cells, which was
      unaffected by the presence of IFNgamma. We conclude that in healthy epithelium,
      the most superficial cells at the end of their life cycle are simply desquamated.
      In contrast, RAU is characterized by top-to-bottom apoptosis such that dead cells
      may slough off, leading to an ulcer. Because of a lack of scavenging anti
      inflammatory macrophages, apoptotic cells probably undergo secondary necrosis
      releasing proinflammatory danger signals, which may contribute to the peripheral
      inflammatory halo. This is supported by self-DNA-induced TNFalpha synthesis. In
      contrast to TLR4- and TLR2-binding lipopolysaccharide used as a positive control,
      disulfide-HMGB1 did not stimulate proinflammatory cytokines. 

PMID- 25861802
TI  - Enforcing Enrollment in Health Insurance Exchanges: Evidence From the
      Netherlands, Switzerland, and Germany.
AB  - Experience from the Netherlands, Switzerland, and Germany suggests that there may
      be a looming problem concerning uninsured individuals and defaulters that could
      derail coverage projection numbers in the United States under the Affordable Care
      Act. In those countries, the young, people with migrant backgrounds, and those
      with lower incomes-precisely the groups the Affordable Care Act is seeking to
      cover-are overrepresented in the numbers of the uninsured and defaulters,
      frequently because of difficulty in paying for their premiums. In these three
      countries, penalties or suspension of coverage alone has not led everyone to
      purchase coverage or prevented some from defaulting. Help in addressing the
      vulnerable position of the uninsured may be needed. Examples include using a
      multifaceted approach in which public authorities help with debt restructuring,
      freeing some funds in the exchanges to help vulnerable groups, and compensating
      insurers for their outstanding payments if they follow an agreed protocol instead
      of canceling coverage. 

PMID- 25861803
TI  - Implementation of Patient-Centered Medical Homes in Adult Primary Care Practices.
AB  - There has been relatively little empirical evidence about the effects of patient
      centered medical home (PCMH) implementation on patient-related outcomes and
      costs. Using a longitudinal design and a large study group of 2,218 Michigan
      adult primary care practices, our study examined the following research
      questions: Is the level of, and change in, implementation of PCMH associated with
      medical surgical cost, preventive services utilization, and quality of care in
      the following year? Results indicated that both level and amount of change in
      practice implementation of PCMH are independently and positively associated with
      measures of quality of care and use of preventive services, after controlling for
      a variety of practice, patient cohort, and practice environmental
      characteristics. Results also indicate that lower overall medical and surgical
      costs are associated with higher levels of PCMH implementation, although change
      in PCMH implementation did not achieve statistical significance. 

PMID- 25861804
TI  - 2014 UK national guideline for the management of anogenital herpes.
AB  - These guidelines concern the management of anogenital herpes simplex virus
      infections in adults and give advice on diagnosis, management, and counselling of
      patients. This guideline replaces the 2007 BASHH herpes guidelines and includes
      new sections on herpes proctitis, key points to cover with patients regarding
      transmission and removal of advice on the management of HSV in pregnancy which
      now has a separate joint BASHH/RCOG guideline. 

PMID- 25861805
TI  - RETRACTED: Dynamic analysis of viral load, T-lymphocyte subset count, gamma-gt
      and lactate of pre-therapy and post-treatment AIDS patients.
AB  - Dynamic analysis of viral load, T-lymphocyte subset count, gamma-gt and lactate
      of pre-therapy and post-treatment AIDS patientsGuosheng Su, Shan Li, Xue Qin,
      Xiaolu Luo, Wanhong Huang, Shanqiu Wei, Hanzhen Su, Shunda Luo, and Zeduan LiuThe
      International Journal of STD & AIDS first published the above article on April 9,
      2015 as doi:10.1177/0956462415576424The above article has now been withdrawn from
      publication.

PMID- 25861806
TI  - Natural history of chronic hepatitis B virus infection in childhood and efficacy
      of interferon therapy.
AB  - OBJECTIVES: In short-term observations, interferon (IFN) therapy has been shown
      to be effective in producing both biochemical and virological responses in
      children with chronic hepatitis B virus (HBV) infection. However, in long-term
      follow up, no studies have shown a clear advantage of IFN therapy during
      childhood. We conducted a retrospective study on the sustained effect of IFN
      therapy among a Japanese pediatric population. METHODS AND SUBJECTS: A
      retrospective study was performed on 155 children with chronic HBV infection who
      were followed in two affiliated hospitals during the period from 1986 to 2013.
      RESULTS: The 155 patients comprised 97 males and 58 female. Infection route was
      maternal transmission in 96/155 patients. HBV genotype was A in 17, B in 6, and C
      in 51 patients. IFN therapy was performed in 48 patients. One year after the
      completion of IFN therapy, normalization of alanine aminotransferase (ALT) and
      lower viral levels (<10(4) copies/ml) was observed in 43 and 29 patients,
      respectively. The sustained effects of IFN therapy were evaluated by comparison
      between 43 hepatitis B e-antigen (HBeAg)-positive patients treated with IFN and
      67 patients with chronic hepatitis B observed without IFN therapy. A Cox's
      proportional hazard analysis showed a higher seroconversion rate in the IFN group
      than in the untreated group (p = 0.003). Similarly, there were higher rates of
      ALT normalization and lower viral levels in the IFN group than in the untreated
      group (p = 0.001 for both). CONCLUSION: IFN therapy showed sustained effects for
      achieving ALT normalization and HBeAg seroconversion and for reducing the viral
      load in children with chronic hepatitis B.

PMID- 25861807
TI  - Visual search for emotional expressions: Effect of stimulus set on anger and
      happiness superiority.
AB  - Prior reports of preferential detection of emotional expressions in visual search
      have yielded inconsistent results, even for face stimuli that avoid obvious
      expression-related perceptual confounds. The current study investigated
      inconsistent reports of anger and happiness superiority effects using face
      stimuli drawn from the same database. Experiment 1 excluded procedural
      differences as a potential factor, replicating a happiness superiority effect in
      a procedure that previously yielded an anger superiority effect. Experiments 2a
      and 2b confirmed that image colour or poser gender did not account for prior
      inconsistent findings. Experiments 3a and 3b identified stimulus set as the
      critical variable, revealing happiness or anger superiority effects for two
      partially overlapping sets of face stimuli. The current results highlight the
      critical role of stimulus selection for the observation of happiness or anger
      superiority effects in visual search even for face stimuli that avoid obvious
      expression related perceptual confounds and are drawn from a single database. 

PMID- 25861808
TI  - The effect of 14 weeks of vitamin D3 supplementation on antimicrobial peptides
      and proteins in athletes.
AB  - Heavy training is associated with increased respiratory infection risk and
      antimicrobial proteins are important in defence against oral and respiratory
      tract infections. We examined the effect of 14 weeks of vitamin D3
      supplementation (5000 IU/day) on the resting plasma cathelicidin concentration
      and the salivary secretion rates of secretory immunoglobulin A (SIgA),
      cathelicidin, lactoferrin and lysozyme in athletes during a winter training
      period. Blood and saliva were obtained at the start of the study from 39 healthy
      men who were randomly allocated to vitamin D3 supplement or placebo. Blood
      samples were also collected at the end of the study; saliva samples were
      collected after 7 and 14 weeks. Plasma total 25(OH)D concentration increased by
      130% in the vitamin D3 group and decreased by 43% in the placebo group (both P =
      0.001). The percentage change of plasma cathelicidin concentration in the vitamin
      D3 group was higher than in the placebo group (P = 0.025). Only in the vitamin D3
      group, the saliva SIgA and cathelicidin secretion rates increased over time (both
      P = 0.03). A daily 5000 IU vitamin D3 supplement has a beneficial effect in up
      regulating the expression of SIgA and cathelicidin in athletes during a winter
      training period, which could improve resistance to respiratory infections.

PMID- 25861809
TI  - Angiotensin II exerts dual actions on sodium-glucose transporter 1-mediated
      transport in the human jejunal mucosa.
AB  - OBJECTIVES: Intestinal glucose absorption is mainly mediated via the sodium
      glucose transporter 1 (SGLT1) at the apex of the enterocytes, whereas the glucose
      transporter 2 (GLUT2) provides a basolateral exit. It has been shown in rats that
      Angiotensin II (AngII), the principal mediator of renin-angiotensin system (RAS),
      inhibits jejunal SGLT1-mediated glucose absorption. The aim of the present study
      was to investigate if a similar mechanism exists also in the human jejunal
      mucosa. MATERIAL AND METHODS: Enteroscopy with mucosal biopsy sampling was
      performed in 28 healthy volunteers. Functional assessments were performed in
      Ussing chambers using a pharmacological approach. Western blotting and
      immunohistochemistry were used to assess the presence of the AngII type 1 (AT1R)
      and type 2 receptor (AT2R), as well as the glucose transporters SGLT1 and GLUT2.
      RESULTS: Exposure of the mucosa to 10 mM glucose elicited a ~50% increase in the
      epithelium-generated current (Iep). This glucose-induced electrogenic response
      was sensitive to the competitive SGLT1 inhibitor phlorizin, but not to AngII when
      given alone. AngII combined with the AT2R blocker PD123319 markedly inhibited the
      response. AngII in combination with the AT1R antagonist losartan tended to
      increase the electrogenic response, whereas direct activation of AT2R using the
      agonist C21 significantly enhanced the mucosal response to glucose. The AT1R and
      AT2R as well as SGLT1 and GLUT2 were detected inside the human enterocytes.
      CONCLUSIONS: The pharmacological analysis indicated that activation of AT1R
      inhibits, whereas activation of AT2R enhances SGLT1-mediated glucose transport in
      the human jejunal mucosa.

PMID- 25861810
TI  - Impact of age, BMI and HbA1c levels on the genome-wide DNA methylation and mRNA
      expression patterns in human adipose tissue and identification of epigenetic
      biomarkers in blood.
AB  - Increased age, BMI and HbA1c levels are risk factors for several non-communicable
      diseases. However, the impact of these factors on the genome-wide DNA methylation
      pattern in human adipose tissue remains unknown. We analyzed the DNA methylation
      of ~480 000 sites in human adipose tissue from 96 males and 94 females and
      related methylation to age, BMI and HbA1c. We also compared epigenetic signatures
      in adipose tissue and blood. Age was significantly associated with both altered
      DNA methylation and expression of 1050 genes (e.g. FHL2, NOX4 and PLG).
      Interestingly, many reported epigenetic biomarkers of aging in blood, including
      ELOVL2, FHL2, KLF14 and GLRA1, also showed significant correlations between
      adipose tissue DNA methylation and age in our study. The most significant
      association between age and adipose tissue DNA methylation was found upstream of
      ELOVL2. We identified 2825 genes (e.g. FTO, ITIH5, CCL18, MTCH2, IRS1 and SPP1)
      where both DNA methylation and expression correlated with BMI. Methylation at
      previously reported HIF3A sites correlated significantly with BMI in females
      only. HbA1c (range 28-46 mmol/mol) correlated significantly with the methylation
      of 711 sites, annotated to, for example, RAB37, TICAM1 and HLA-DPB1. Pathway
      analyses demonstrated that methylation levels associated with age and BMI are
      overrepresented among genes involved in cancer, type 2 diabetes and
      cardiovascular disease. Our results highlight the impact of age, BMI and HbA1c on
      epigenetic variation of candidate genes for obesity, type 2 diabetes and cancer
      in human adipose tissue. Importantly, we demonstrate that epigenetic biomarkers
      in blood can mirror age-related epigenetic signatures in target tissues for
      metabolic diseases such as adipose tissue. 

PMID- 25861812
TI  - Sudden cardiac death in patients with diabetes mellitus and chronic heart
      failure.
AB  - In patients with diabetes mellitus, around 50% of deaths due to cardiovascular
      causes are sudden cardiac deaths. The prevalence of diabetes in cohorts with
      chronic heart failure is increasing, and while sudden cardiac death is an
      increasingly rare mode of death in chronic heart failure patients as a whole, the
      risk of this outcome remains high in those with diabetes. This review summarises
      the current knowledge on the incidence of sudden cardiac death in patients with
      diabetes and chronic heart failure, before discussing the causes of the excess
      risk seen in those with these coexistent conditions. We then describe current
      strategies for risk stratification and prevention of sudden cardiac death in
      these patients before discussing the priorities for further study in this area. 

PMID- 25861813
TI  - Role of lipoprotein(a) in predicting the severity of new on-set coronary artery
      disease in type 2 diabetics: A Gensini score evaluation.
AB  - The objective of the study was to investigate the usefulness of serum
      lipoprotein(a) level in predicting the severity of new on-set coronary artery
      disease in type 2 diabetics. A total of 1254 new on-set, consecutive coronary
      artery disease patients were classified into two groups: diabetes group (n = 380)
      and non-diabetes group (n = 874). The relationship between serum lipoprotein(a)
      levels and the severity of coronary artery disease assessed by Gensini score was
      analysed. Data showed that the diabetes group had higher serum triglyceride and
      high sensitivity C-reactive protein levels but lower high-density lipoprotein
      cholesterol levels (all p < 0.05). The multivariate logistic regression analysis
      suggested that lipoprotein(a) was an independent predictor for high Gensini score
      (odds ratio = 1.82, 95% confidence interval: 1.10-3.12, p = 0.029) after
      adjusting for traditional cardiovascular risk factors. Additionally,
      lipoprotein(a) levels were positively correlated with Gensini score (rho = 0.15,
      p = 0.014) and significantly elevated according to the tertiles of Gensini score
      (p = 0.008) in diabetics. However, no such results were observed in non
      diabetics. Our data indicate that lipoprotein(a) is an independent predictor for
      the severity of new on-set coronary artery disease patients accompanied by type 2
      diabetes, suggesting that these patients may benefit from lipoprotein(a)
      management in clinical assessment. 

PMID- 25861814
TI  - Functional Recovery of Carbon Nanotube/Nafion Nanocomposite in Rat Model of
      Spinal Cord Injury.
AB  - BACKGROUND: Acute spinal cord injury (ASCI) can lead to paraplegia or
      quadriplegia, the treatment of which has been a major problem. New therapeutic
      approaches in developing carbon nanotubes (CNT) functionalized with the Nafion
      nanocomposite, a sulfonated tetrafluoroethylene copolymer, have been shown to
      increase the length of selected neurites in vitro. OBJECTIVE: We hypothesized
      that the administration of the CNT/Nafion nanocomposite after experimental SCI
      will promote regeneration of axons into the lesion cavity and the functional
      recovery of the hind limbs in a rat model. METHODS: To evaluate this hypothesis
      through this experimental research paper, transection SCI was induced at the T9
      T10 vertebral level in adult female rats. One week after transection, the
      epicenter of the lesion was injected with 25 lL of vehicle (saline), or 1 lg/mL,
      10 lg/mL, or 100 lg/mL of CNT/Nafion nanocomposite. Behavioral analysis was
      carried out by assessing tail flick, chronic pain or mechanical allodynia, motor
      coordination, and the results of the rotarod test performed pre- and post
      surgery, on days 3, 7, 14, 21 and 28, using the tail flick analysis, Noldus
      CatWalk gait analysis, open-field locomotor test, and Rotarod test. At 28 days
      post-injection, the rats were euthanized and spinal cord tissue was extracted.
      RESULTS: We found that post-SCI, administration of the CNT/Nafion nanocomposite
      resulted in decreased lesion volume, increased neurofilament-positive fibers and
      corticospinal tract fibers in the lesion, and no increase in reactive gliosis (P
      < 0.001). Additionally, post-SCI administration of CNT/Nafion nanocomposite
      induced a modest improvement in hind limb locomotor recovery without inducing
      hyperalgesia. CONCLUSION: These data suggest that the CNT/Nafion nanocomposite
      may be an effective material to promote axonal repair and regeneration after SCI.

PMID- 25861815
TI  - Association of stillbirth with ambient air pollution in a California cohort
      study.
AB  - Recent studies have suggested an association between air pollution and
      stillbirth. In this California study, we examined the records of 13,999
      stillbirths and 3,012,270 livebirths occurring between 1999 and 2009. Using a
      retrospective cohort design and logistic regression models, we calculated the
      odds of stillbirth associated with each pollutant exposure by trimester and
      throughout the entire pregnancy. Covariates considered in the model included
      infant sex, maternal demographic characteristics, season of last menstrual
      period, apparent temperature, air basin of mother's residence, and year of
      conception. In single-pollutant models, we found that a 10-ug/m(3) increase in
      particulate matter with an aerodynamic diameter less than or equal to 2.5 um
      (odds ratio (OR) = 1.06, 95% confidence interval (CI): 0.99, 1.13) and a 10-ppb
      increase in nitrogen dioxide (OR = 1.08, 95% CI: 1.03, 1.13) during the entire
      pregnancy were associated with stillbirth. A 10-ppb increase in ozone exposure
      during the third trimester was also associated with a slightly elevated risk (OR
      = 1.03, 95% CI: 1.01, 1.05). These ozone and nitrogen dioxide findings were
      fairly stable after adjustment in 2-pollutant models. However, adjustment for
      nitrogen dioxide attenuated the full-pregnancy-particulate matter relationship.
      No significant associations were found for sulfur dioxide or carbon monoxide.
      These findings support growing evidence of an association between air pollution
      and adverse birth outcomes. 

PMID- 25861816
TI  - Re: "The Association of Common Variants in PCSK1 With Obesity: A HuGE Review and
      Meta-Analysis".

PMID- 25861817
TI  - The authors reply.

PMID- 25861811
TI  - A common variant near TGFBR3 is associated with primary open angle glaucoma.
AB  - Primary open angle glaucoma (POAG), a major cause of blindness worldwide, is a
      complex disease with a significant genetic contribution. We performed Exome Array
      (Illumina) analysis on 3504 POAG cases and 9746 controls with replication of the
      most significant findings in 9173 POAG cases and 26 780 controls across 18
      collections of Asian, African and European descent. Apart from confirming strong
      evidence of association at CDKN2B-AS1 (rs2157719 [G], odds ratio [OR] = 0.71, P =
      2.81 * 10(-33)), we observed one SNP showing significant association to POAG
      (CDC7-TGFBR3 rs1192415, ORG-allele = 1.13, Pmeta = 1.60 * 10(-8)). This
      particular SNP has previously been shown to be strongly associated with optic
      disc area and vertical cup-to-disc ratio, which are regarded as glaucoma-related
      quantitative traits. Our study now extends this by directly implicating it in
      POAG disease pathogenesis. 

PMID- 25861818
TI  - Parallel Structural Evolution of Mitochondrial Ribosomes and OXPHOS Complexes.
AB  - The five macromolecular complexes that jointly mediate oxidative phosphorylation
      (OXPHOS) in mitochondria consist of many more subunits than those of bacteria,
      yet, it remains unclear by which evolutionary mechanism(s) these novel subunits
      were recruited. Even less well understood is the structural evolution of
      mitochondrial ribosomes (mitoribosomes): while it was long thought that their
      exceptionally high protein content would physically compensate for their uniquely
      low amount of ribosomal RNA (rRNA), this hypothesis has been refuted by
      structural studies. Here, we present a cryo-electron microscopy structure of the
      73S mitoribosome from Neurospora crassa, together with genomic and proteomic
      analyses of mitoribosome composition across the eukaryotic domain. Surprisingly,
      our findings reveal that both structurally and compositionally, mitoribosomes
      have evolved very similarly to mitochondrial OXPHOS complexes via two distinct
      phases: A constructive phase that mainly acted early in eukaryote evolution,
      resulting in the recruitment of altogether approximately 75 novel subunits, and a
      reductive phase that acted during metazoan evolution, resulting in gradual length
      reduction of mitochondrially encoded rRNAs and OXPHOS proteins. Both phases can
      be well explained by the accumulation of (slightly) deleterious mutations and
      deletions, respectively, in mitochondrially encoded rRNAs and OXPHOS proteins. We
      argue that the main role of the newly recruited (nuclear encoded) ribosomal- and
      OXPHOS proteins is to provide structural compensation to the mutationally
      destabilized mitochondrially encoded components. While the newly recruited
      proteins probably provide a selective advantage owing to their compensatory
      nature, and while their presence may have opened evolutionary pathways toward
      novel mitochondrion-specific functions, we emphasize that the initial events that
      resulted in their recruitment was nonadaptive in nature. Our framework is
      supported by population genetic studies, and it can explain the complete
      structural evolution of mitochondrial ribosomes and OXPHOS complexes, as well as
      many observed functions of individual proteins.

PMID- 25861819
TI  - Prokaryotic nucleotide composition is shaped by both phylogeny and the
      environment.
AB  - The causes of the great variation in nucleotide composition of prokaryotic
      genomes have long been disputed. Here, we use extensive metagenomic and whole
      genome data to demonstrate that both phylogeny and the environment shape
      prokaryotic nucleotide content. We show that across environments, various phyla
      are characterized by different mean guanine and cytosine (GC) values as well as
      by the extent of variation on that mean value. At the same time, we show that GC
      content varies greatly as a function of environment, in a manner that cannot be
      entirely explained by disparities in phylogenetic composition. We find
      environmentally driven differences in nucleotide content not only between highly
      diverged environments (e.g., soil, vs. aquatic vs. human gut) but also within a
      single type of environment. More specifically, we demonstrate that some human
      guts are associated with a microbiome that is consistently more GC-rich across
      phyla, whereas others are associated with a more AT-rich microbiome. These
      differences appear to be driven both by variations in phylogenetic composition
      and by environmental differences-which are independent of these phylogenetic
      composition differences. Combined, our results demonstrate that both phylogeny
      and the environment significantly affect nucleotide composition and that the
      environmental differences affecting nucleotide composition are far subtler than
      previously appreciated.

PMID- 25861820
TI  - Extensive Capsule Locus Variation and Large-Scale Genomic Recombination within
      the Klebsiella pneumoniae Clonal Group 258.
AB  - Klebsiella pneumoniae clonal group (CG) 258, comprising sequence types (STs) 258,
      11, and closely related variants, is associated with dissemination of the K.
      pneumoniae carbapenemase (KPC). Hospital outbreaks of KPC CG258 infections have
      been observed globally and are very difficult to treat. As a consequence, there
      is renewed interest in alternative infection control measures such as vaccines
      and phage or depolymerase treatments targeting the K. pneumoniae polysaccharide
      capsule. To date, 78 immunologically distinct capsule variants have been
      described in K. pneumoniae. Previous investigations of ST258 and a small number
      of closely related strains suggested that capsular variation was limited within
      this clone; only two distinct ST258 capsule polysaccharide synthesis (cps) loci
      have been identified, both acquired through large-scale recombination events (>50
      kb). In contrast to previous studies, we report a comparative genomic analysis of
      the broader K. pneumoniae CG258 (n = 39). We identified 11 different cps loci
      within CG258, indicating that capsular switching is actually common within the
      complex. We observed several insertion sequences (IS) within the cps loci, and
      show further intraclone diversification of two cps loci through IS activity. Our
      data also indicate that several large-scale recombination events have shaped the
      genomes of CG258, and that definition of the complex should be broadened to
      include ST395 (also reported to harbor KPC). As only the second report of
      extensive intraclonal cps variation among Gram-negative bacterial species, our
      findings alter our understanding of the evolution of these organisms and have key
      implications for the design of control measures targeting K. pneumoniae capsules.

PMID- 25861821
TI  - Cardiac autonomic control in the obstructive sleep apnea.
AB  - INTRODUCTION: The sympathetic activation is considered to be the main mechanism
      involved in the development of cardiovascular diseases in obstructive sleep apnea
      (OSA). The heart rate variability (HRV) analysis represents a non-invasive tool
      allowing the study of the autonomic nervous system. The impairment of HRV
      parameters in OSA has been documented. However, only a few studies tackled the
      dynamics of the autonomic nervous system during sleep in patients having OSA.
      AIMS: To analyze the HRV over sleep stages and across sleep periods in order to
      clarify the impact of OSA on cardiac autonomic modulation. The second objective
      is to examine the nocturnal HRV of OSA patients to find out which HRV parameter
      is the best to reflect the symptoms severity. METHODS: The study was
      retrospective. We have included 30 patients undergoing overnight polysomnography.
      Subjects were categorized into two groups according to apnea-hypopnea index
      (AHI): mild-to-moderate OSAS group (AHI: 5-30) and severe OSAS group (AHI>30).
      The HRV measures for participants with low apnea-hypopnea indices were compared
      to those of patients with high rates of apnea-hypopnea across the sleep period
      and sleep stages. RESULTS: HRV measures during sleep stages for the group with
      low rates of apnea-hypopnea have indicated a parasympathetic activation during
      non-rapid eye movement (NREM) sleep. However, no significant difference has been
      observed in the high AHI group except for the mean of RR intervals (mean RR). The
      parasympathetic activity tended to increase across the night but without a
      statistical difference. After control of age and body mass index, the most
      significant correlation found was for the mean RR (p=0.0001, r=-0.248).
      CONCLUSION: OSA affects sympathovagal modulation during sleep, and this impact
      has been correlated to the severity of the disease. The mean RR seemed to be a
      better index allowing the sympathovagal balance appreciation during the night in
      OSA.

PMID- 25861822
TI  - Serological diagnosis of bovine neosporosis: a Bayesian evaluation of two
      antibody ELISA tests for in vivo diagnosis in purchased and abortion cattle.
AB  - Currently, there are no perfect reference tests for the in vivo detection of
      Neospora caninum infection. Two commercial N caninum ELISA tests are currently
      used in Belgium for bovine sera (TEST A and TEST B). The goal of this study is to
      evaluate these tests used at their current cut-offs, with a no gold standard
      approach, for the test purpose of (1) demonstration of freedom of infection at
      purchase and (2) diagnosis in aborting cattle. Sera of two study populations,
      Abortion population (n=196) and Purchase population (n=514), were selected and
      tested with both ELISA's. Test results were entered in a Bayesian model with
      informative priors on population prevalences only (Scenario 1). As sensitivity
      analysis, two more models were used: one with informative priors on test
      diagnostic accuracy (Scenario 2) and one with all priors uninformative (Scenario
      3). The accuracy parameters were estimated from the first model: diagnostic
      sensitivity (Test A: 93.54 per cent-Test B: 86.99 per cent) and specificity (Test
      A: 90.22 per cent-Test B: 90.15 per cent) were high and comparable (Bayesian P
      values >0.05). Based on predictive values in the two study populations, both
      tests were fit for purpose, despite an expected false negative fraction of +/-0.5
      per cent in the Purchase population and +/-5 per cent in the Abortion population.
      In addition, a false positive fraction of +/-3 per cent in the overall Purchase
      population and +/-4 per cent in the overall Abortion population was found.

PMID- 25861823
TI  - What do European veterinary codes of conduct actually say and mean? A case study
      approach.
AB  - Codes of Professional Conduct (CPCs) are pivotal instruments of self-regulation,
      providing the standards to which veterinarians should, and sometimes must,
      comply. Despite their importance to the training and guidance of veterinary
      professionals, research is lacking on the scope and emphasis of the requirements
      set out in veterinary CPCs. This paper provides the first systematic
      investigation of veterinary CPCs. It relies on a case study approach, combining
      content and thematic analyses of five purposively selected European CPCs:
      Federation of Veterinarians of Europe (FVE), Denmark, Ireland, Portugal and the
      UK. Eight overarching themes were identified, including 'definitions and framing
      concepts', 'duties to animals', 'duties to clients', 'duties to other
      professionals', 'duties to competent authorities', 'duties to society',
      'professionalism' and 'practice-related issues'. Some differences were observed,
      which may be indicative of different approaches to the regulation of the
      veterinary profession in Europe (which is reflected in having a 'code of ethics'
      or a 'code of conduct'), cultural differences on the status of animals in
      society, and regulatory bodies' proactivity in adapting to professional needs and
      to societal changes regarding the status of animals. These findings will
      contribute to an improved understanding of the roles of CPCs in regulating the
      veterinary profession in Europe. 

PMID- 25861824
TI  - Identification and quantification of factors affecting neonatal immunological
      transfer in dairy calves in the UK.
AB  - The object of the study was to quantify the prevalence of failure of passive
      transfer in UK dairy farms and to identify variables that had a significant
      impact on the rate of immunological transfer. In a six-month study of 444
      calvings from seven UK dairy farms, 26 per cent of calves failed to receive
      adequate immunoglobulin transfer as judged by a plasma total protein (pTP)
      concentration less than 5.6 g/dl. Colostrum immunoglobulin concentration,
      indirectly measured using Brix refractometry, showed wide variations with samples
      ranging from 10.3 to 34.7 Brix units. Thirty-seven per cent of samples were below
      the suggested cut-off Brix score for colostrum quality of 22 per cent. Potential
      associations between covariates and plasma protein concentration were
      investigated using multiple linear regression models. The covariate with the
      greatest impact on the pTP concentration was the farm on which the calf was born
      (P<0.05). A significant but small association was demonstrated between colostrum
      immunoglobulin concentration and calf pTP concentration (P<0.01). Multiple linear
      regression models suggested that the time of colostrum collection after calving,
      parity of the dam, and the individual farm were associated with the Brix
      measurements (P<0.05). This study suggested that veterinary review of colostrum
      protocols on farm with emphasis on prompt collection and dosing after calving
      remains a simple and effective measure to improve passive transfer and thus calf
      health on UK dairy farms. 

PMID- 25861825
TI  - Clinical and radiographic features of contagious ovine digital dermatitis and a
      novel lesion grading system.
AB  - Contagious ovine digital dermatitis (CODD) is an infectious foot disease of sheep
      causing severe lameness. Diagnosis is currently made using broad anecdotal
      descriptions. The aim of this study was to systematically and formally describe
      the clinical presentation of the disease in terms of (1) a lesion grading system;
      (2) associated radiographic changes and (3) severity of associated lameness. A
      five-point lesion grading system was developed and applied to 908 sheep affected
      by CODD from six farms. Sheep with lesions typical of each grade were euthanased
      and their feet radiographed. Radiographic abnormalities including soft tissue and
      bony changes were evident in feet with lesions graded 2-5. In order to quantify
      the welfare impact of CODD, all the 908 sheep were locomotion scored. Five
      hundred and eighty-five (64.5% (95% CI 61.4% to 67.6%)) were lame. The locomotion
      score for affected sheep increased with worsening pathological changes. Once
      healing had begun the locomotion score decreased. In conclusion the five-point
      grading system may be used to clinically describe stages of CODD lesions. The
      radiographic changes revealed examples of deeper pathological changes and there
      was a strong association between the lesion grading system and locomotion score
      in affected sheep. 

PMID- 25861826
TI  - Multilocus Sequence Analysis of the redefined clade Scophthalmi in the genus
      Vibrio.
AB  - A Multilocus Sequence Analysis (MLSA) was performed on members of the Scophthalmi
      clade in the genus Vibrio, including type and reference strains of the species V.
      scophthalmi, V. ichthyoenteri, and 39 strains phenotypically identified as Vibrio
      ichthyoenteri-like, with the aim of better defining boundaries between these two
      closely related, fish-associated species. The type strain of V. ponticus,
      recently added to the clade Scophthalmi, was also included. The study was based
      on partial sequences of the protein-coding housekeeping genes rpoD, mreB, recA,
      ftsZ, and gyrB, and the 16S rRNA. While the 16S rRNA gene-based trees were unable
      to pull apart members of V. scophthalmi or V. ichthyoenteri, both the other
      individual gene trees and the trees obtained from the five-genes concatenated
      sequences were able to consistently differentiate four subclades within the main
      clade, corresponding to the bona fide V. scophthalmi, V. ichthyoenteri, and two
      small ones that may represent a new species each. The best genes to differentiate
      V. scophthalmi from V. ichthyoenteri were rpoD, recA, and mreB. Vibrio ponticus
      failed to associate to the clade in the MLSA and in most single gene trees for
      which it should not be considered part of it. In this study we also confirm using
      genomic indexes that V. ichthyoenteri and V. scophthalmi are two separate
      species. 

PMID- 25861827
TI  - Effects of anti-inflammatory therapy on bursting pressure of colonic anastomosis
      in murine dextran sulfate sodium induced colitis.
AB  - BACKGROUND: The aim of this study was to examine the effect of colitis and anti
      inflammatory therapies on the healing of colonic anastomoses in mice. METHODS:
      Female C57BL/6 mice were randomized into eight groups; four groups receiving
      plain tap-water and four groups receiving dextran sulfate sodium. Intra
      peritoneal treatment was given therapeutically for 14 days with placebo,
      prednisolone, azathioprine, or infliximab (IFX). Colonic anastomoses were
      performed and bursting pressure (BP) measurements were recorded and the
      inflammation evaluated with histology and zymography. RESULTS: The mice with
      colitis had a more active inflammation based on histology and bowel weight
      compared with the tap water group, 8.3 (7.6-9.5) mg/mm and 5.5 (4.8-6.2) mg/mm
      respectively (p < 0.0001). Similarly mice with colitis receiving placebo had a
      more active inflammation, 12.8 (10.6-15.0) mg/mm, which differed significantly
      from all the other therapy arms among the colitic mice; prednisolone 8.1 (7.5
      9.1) mg/mm (p = 0.014), azathioprine 8.2 (7.0-8.5) mg/mm (p = 0.0046), IFX 6.7
      (6.4-7.9) mg/mm (p = 0.0055). BP for the placebo group was 90.0 (71.5-102.8) mmHg
      and did not differ from azathioprine or IFX groups, 84.4 (70.5-112.5) and 92.3
      (75.8-122.3) mmHg respectively. In contrast BP for the prednisolone group was
      significantly decreased compared to placebo, 55.5 (42.8-73.0) mmHg (p = 0.0004).
      CONCLUSIONS: All therapies had a beneficial effect on the colitis. An impaired BP
      of colonic anastomoses was noted after preoperative steroids but not after
      azathioprine or IFX in this model.

PMID- 25861828
TI  - Sudden cardiac death during physical exercise: Characteristics of victims and
      autopsy findings.
AB  - OBJECTIVE: To provide data on the risk factors and characteristics of subjects
      who experience sudden cardiac death (SCD) during physical exercise. METHODS AND
      RESULTS: We assessed the characteristics and the medico-legal autopsy findings of
      SCD victims who had experienced a witnessed fatal cardiac arrest at rest (n =
      876) or in relation to physical exercise (n = 328) in the Finnish Study of
      Genotype and Phenotype Characteristics of SCD (FinGesture). A total of 876 (73%)
      witnessed SCDs occurred at rest (R group) and 328 (27%) during or immediately
      after physical exercise (PE group). Male gender was more common in the PE group
      compared to the R group (309/328, 94% versus 678/876, 77%, P < 0.001). Coronary
      artery disease was a more common structural heart disease than non-ischemic
      disease at autopsy when SCD was exercise-triggered (299/328, 91% versus 657/876,
      75%, P < 0.001). Myocardial scarring and cardiac hypertrophy were more commonly
      found at autopsy in the PE group (194/328, 59% versus 370/876, 42%, P < 0.001;
      243/328, 74% versus 585/876, 67%, P = 0.012, respectively). Skiing, cycling, and
      snow shoveling were the most common modes of exercise at the time of SCD.
      CONCLUSIONS: SCD during or immediately after exercise is related to male gender,
      ischemic heart disease, cardiac hypertrophy, and myocardial scarring.

PMID- 25861829
TI  - Molecular mechanisms of the progression of myelodysplastic syndrome to secondary
      acute myeloid leukaemia and implication for therapy.
AB  - Myelodysplastic syndrome (MDS) includes a heterogeneous group of clonal
      haematological stem cell disorders characterized by dysplasia, cytopenias,
      ineffective haematopoiesis, and an increased risk of progression to acute myeloid
      leukaemia (AML), which is also called secondary AML (sAML). Approximately one
      third of patients with MDS will progress to sAML within a few months to a few
      years, and this type of transformation is more common and rapid in patients with
      high-risk MDS (HR-MDS). However, the precise mechanisms underlying the evolution
      of MDS to sAML remain unclear. Currently, chemotherapy for sAML has minimal
      efficacy. The only method of curing patients with sAML is allogeneic
      haematopoietic stem cell transplantation (Allo-HSCT). Unfortunately, only a few
      patients are appropriate for transplantation because this disease primarily
      affects older adult patients. Additionally, compared to de novo AML, sAML is more
      difficult to cure, and the prognosis is often worse. Therefore, it is important
      to clarify the molecular mechanisms of the progression of MDS to sAML and to
      explore the potent drugs for clinical use. This review will highlight several
      molecular mechanisms of the progression of MDS to sAML and new therapeutic
      strategies of this disease. 

PMID- 25861830
TI  - High risk of abnormal QT prolongation in the early morning in diabetic and non
      diabetic patients with severe hypoglycemia.
AB  - BACKGROUND: Several studies have suggested that the occurrence of severe
      hypoglycemia during sleep may be more dangerous for cardiac arrhythmia than that
      in the day-time. METHODS: We performed a retrospective study between January 2006
      and March 2012 to assess electrocardiograms during severe hypoglycemia in
      patients with or without diabetes. RESULTS: A total of 59,602 patients who
      visited the emergency room by ambulance were screened, and 287 patients with
      severe hypoglycemia were enrolled. The median blood glucose levels in patients
      with (DM, n = 192) and without diabetes (non-DM, n = 95) were 30 and 45 mg/dL,
      respectively. During severe hypoglycemia, the incidence of abnormal QT
      prolongation was significantly higher in the early morning (4-10 a.m.) than at
      other times (DM group, 74.3% versus 54.1%, P = 0.02; non-DM group, 78.3% versus
      50.0%, P = 0.01). Multivariate logistic regression analysis identified the
      occurrence of severe hypoglycemia in the early morning as a strong factor for
      abnormal QT prolongation (DM group, odds ratio [OR] 2.80, 95% confidence interval
      [CI] 1.15-6.80, P = 0.02; non-DM group, OR 4.53, 95% CI 1.30-15.74, P = 0.01).
      CONCLUSIONS: The incidence of abnormal QT prolongation during severe hypoglycemia
      was significantly higher in the early morning than at all other times,
      independent of the cause of severe hypoglycemia.

PMID- 25861832
TI  - Clinical outcome of adalimumab therapy in patients with ulcerative colitis
      previously treated with infliximab: a Danish single-center cohort study.
AB  - OBJECTIVE: TNF inhibitors are effective in the treatment of ulcerative colitis.
      Adalimumab (ADL), a fully human TNF inhibitor, is increasingly used both as
      primary anti-TNF agent and in patients switching from another TNF inhibitor due
      to treatment failure or side effects. This study investigated clinical outcomes
      of ADL therapy in a clinical setting where infliximab (IFX) had been used as
      first choice of anti-TNF agent, and followed by ADL as second line agent.
      METHODS: Retrospective, observational single-center cohort study including all
      ulcerative colitis patients treated with ADL at a tertiary Danish inflammatory
      bowel disease center until 2014. Clinical outcomes were assessed after 12 and 52
      weeks and classified according to physician's global evaluation. RESULTS: The
      study population comprised 33 patients. Main reasons for switching from IFX to
      ADL were infusion reactions to IFX (45%) or IFX treatment failure (33%). Short
      term efficacy of ADL after 12 weeks revealed 15 patients (45%) with clinical
      response, and 6 (18%) in clinical remission. Twenty-three patients continued ADL
      for more than 12 weeks, and at long-term follow-up after 1 year of ADL treatment,
      eight of these (34%) had clinical response (24% of the entire cohort) and six
      (26%) were in clinical remission (18% of the entire cohort). A total of five
      patients (15%) were colectomized mainly due to primary ADL failure (four of five
      patients). CONCLUSION: Efficacy of ADL therapy in ulcerative colitis patients
      previously treated with IFX appears to be modest in clinical practice, and with
      higher colectomy rates than reported for anti-TNF-naive patients in the
      registration trials.

PMID- 25861831
TI  - 30 day mortality in adult palliative radiotherapy--A retrospective population
      based study of 14,972 treatment episodes.
AB  - BACKGROUND: 30-day mortality (30DM) has been suggested as a clinical indicator of
      the avoidance of harm in palliative radiotherapy within the NHS, but no large
      scale population-based studies exist. This large retrospective cohort study aims
      to investigate the factors that influence 30DM following palliative radiotherapy
      and consider its value as a clinical indicator. METHODS: All radiotherapy
      episodes delivered in a large UK cancer centre between January 2004 and April
      2011 were analysed. Patterns of palliative radiotherapy, 30DM and the variables
      affecting 30DM were assessed. The impact of these variables was assessed using
      logistic regression. RESULTS: 14,972 palliative episodes were analysed. 6334
      (42.3%) treatments were delivered to bone metastases, 2356 (15 7%) to the chest
      for lung cancer and 915 (5.7%) to the brain. Median treatment time was 1day (IQR
      1-7). Overall 30DM was 12.3%. Factors having a significant impact upon 30DM were
      sex, primary diagnosis, treatment site and fractionation schedule (p<0.01).
      CONCLUSION: This is the first large-scale description of 30-day mortality for
      unselected adult palliative radiotherapy treatments. The observed differences in
      early mortality by fractionation support the use of this measure in assessing
      clinical decision making in palliative radiotherapy and require further study in
      other centres and health care systems.

PMID- 25861833
TI  - The divergent effects of fear and disgust on unconscious inhibitory control.
AB  - Previous studies have shown that negative emotional distracters impair conscious
      inhibitory control. Recent research has shown that inhibitory control can be
      triggered unconsciously; therefore, in Experiment 1, we aimed to investigate
      whether negative emotional distracters affect unconscious inhibitory control.
      Furthermore, in Experiment 2, we examined whether fearful and disgusting
      distracters have differential effects on unconscious inhibitory control.
      Participants were instructed to perform a masked Go/No-Go task superimposed on a
      negative or neutral image cue (Experiment 1) or on a fearful, disgusting or
      neutral image cue (Experiment 2). Results showed that negative emotional
      distracters impaired unconscious inhibitory control; furthermore, disgusting
      distracters impeded unconscious inhibitory control when compared to fearful ones.
      This study is the first to provide evidence that fear and disgust may affect
      unconscious inhibitory control differently. These results expand the
      understanding of the relationship between emotions and inhibitory control. 

PMID- 25861834
TI  - Predictive sparse modeling of fMRI data for improved classification, regression,
      and visualization using the k-support norm.
AB  - We explore various sparse regularization techniques for analyzing fMRI data, such
      as the l1 norm (often called LASSO in the context of a squared loss function),
      elastic net, and the recently introduced k-support norm. Employing sparsity
      regularization allows us to handle the curse of dimensionality, a problem
      commonly found in fMRI analysis. In this work we consider sparse regularization
      in both the regression and classification settings. We perform experiments on
      fMRI scans from cocaine-addicted as well as healthy control subjects. We show
      that in many cases, use of the k-support norm leads to better predictive
      performance, solution stability, and interpretability as compared to other
      standard approaches. We additionally analyze the advantages of using the absolute
      loss function versus the standard squared loss which leads to significantly
      better predictive performance for the regularization methods tested in almost all
      cases. Our results support the use of the k-support norm for fMRI analysis and on
      the clinical side, the generalizability of the I-RISA model of cocaine addiction.

PMID- 25861835
TI  - Inflammatory bowel disease therapies discontinued between 2009 and 2014.
AB  - INTRODUCTION: New therapeutic approaches are currently under development, which
      consider the fundamental mechanisms involved in the pathogenesis of inflammatory
      bowel disease (IBD). The disease is associated with inflamed intestinal and
      colonic mucosa in response to the dysregulated immune system. AREAS COVERED: The
      aim of this article is to review drugs that have been designed for the treatment
      of IBD and discontinued between 2009 and 2014. Herein, nine molecules with
      different mechanisms of action are under review. Brodalumab, daclizumab,
      elubrixin and vatelizumab were withdrawn from the Phase II trial due to the lack
      of efficacy. Abatacept was not significantly superior to the placebo in the rate
      of remission and its Phase III trials were stopped. CNDO-210 and Catridecacog
      were discontinued due to safety concerns and lack of efficacy, respectively.
      Finally, NU-206 and alkaline phosphatase also ceased in development during Phase
      I and II tests. EXPERT OPINION: The development in our knowledge and
      understanding of the pathophysiology of IBD and the identification of key
      objectives for the future play significant roles in IBD therapeutic development.
      Furthermore, well-planned clinical trials with concise measures of efficacy and
      safety are required to better decide whether to extend or terminate the
      development process. Some anti-inflammatory cytokines such as IL-2, IL-12, IL-17,
      IL-18, IL-23 and INF-gamma could garner more attention in the future.

PMID- 25861836
TI  - FOLFIRI and Cetuximab Every Second Week for First-Line Treatment of KRAS Wild
      Type Metastatic Colorectal Cancer According to Phosphatase and Tensin Homolog
      Expression: A Phase II Study.
AB  - BACKGROUND: Retrospective studies have suggested that phosphatase and tensin
      homolog (PTEN) expression might predict the efficacy of cetuximab in patients
      with KRAS wild-type metastatic colorectal cancer (mCRC). The present study was
      designed to prospectively evaluate the efficacy of first-line irinotecan,
      fluorouracil, and folinate (FOLFIRI) plus cetuximab every second week according
      to PTEN expression. PATIENTS AND METHODS: Originally, patients with KRAS wild
      type mCRC were randomly assigned to receive either FOLFIRI or cetuximab plus
      FOLFIRI (FOLFIRI-C). After a protocol amendment, the FOLFIRI arm was
      discontinued, and additional patients received FOLFIRI-C. Cox proportional hazard
      models were used to investigate the effect of PTEN and MET expression and BRAF
      and phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha
      mutations on progression-free survival (PFS) and overall survival (OS). RESULTS:
      A total of 35 and 54 patients received FOLFIRI and FOLFIRI-C, respectively. For
      the patients assigned to FOLFIRI and FOLFIRI-C, the median OS was 17.7 and 23.3
      months and the median PFS was 8.2 and 6.6 months, respectively. For patients
      receiving FOLFIRI-C, the loss of PTEN expression did not affect PFS or OS.
      Significant interactions for PFS were detected between the MET expression levels
      (P = .047) and BRAF mutation (P = .018) and treatment. On univariate analysis,
      BRAF mutation was significantly associated with shorter OS for patients receiving
      either FOLFIRI-C (P = .016) or FOLFIRI (P = .035). Multivariate analysis
      confirmed the independent prognostic value of BRAF mutation on OS and that of MET
      expression levels on PFS (P = .025) and OS (P = .028) but only in the patients
      receiving FOLFIRI alone. Adverse events with FOLFIRI-C were consistent with those
      expected from FOLFIRI plus weekly cetuximab. CONCLUSION: Although prospective
      analysis of PTEN did not allow a validation of the prognostic value of this
      biomarker, an every second week cetuximab schedule, in addition to first-line
      FOLFIRI, was effective and well tolerated. The possible predictive value of MET
      expression levels warrants additional investigation.

PMID- 25861838
TI  - The future of medical dosimetry.
AB  - The world of health care delivery is becoming increasingly complex. The purpose
      of this manuscript is to analyze current metrics and analytically predict future
      practices and principles of medical dosimetry. The results indicate five
      potential areas precipitating change factors: a) evolutionary and revolutionary
      thinking processes, b) social factors, c) economic factors, d) political factors,
      and e) technological factors. Outcomes indicate that significant changes will
      occur in the job structure and content of being a practicing medical dosimetrist.
      Discussion indicates potential variables that can occur within each process and
      change factor and how the predicted outcomes can deviate from normative values.
      Finally, based on predicted outcomes, future opportunities for medical
      dosimetrists are given. 

PMID- 25861837
TI  - A Phase II Study of Sorafenib Combined With Cetuximab in EGFR-Expressing, KRAS
      Mutated Metastatic Colorectal Cancer.
AB  - BACKGROUND: Mutations in the KRAS gene predict for resistance to anti-epidermal
      growth factor receptor (EGFR) therapies, including cetuximab. Upregulation of
      vascular endothelial growth factor (VEGF)-A has been implicated in resistance to
      anti-EGFR treatment. Abrogation of the VEGF and RAS/RAF/MEK/ERK pathways has the
      potential to restore cetuximab sensitivity. PATIENTS AND METHODS: Adult patients
      with histologically documented, measurable, EGFR-expressing, KRAS-mutated
      metastatic colorectal cancer (mCRC) that had progressed after 5-fluorouracil
      based regimens were treated with sorafenib 400 mg orally twice daily and
      intravenous cetuximab weekly in 28-day cycles. The primary endpoint was the
      response rate (complete response, partial response, and stable disease at 4
      cycles). The secondary endpoints included plasma biomarker analysis of angiogenic
      cytokines and correlative imaging studies with dynamic contrast-enhanced magnetic
      resonance imaging and zirconium 89-panitumumab. RESULTS: Of the 30 patients
      enrolled, 26 were evaluable for response. Of the 26 patients evaluated, 4 had
      stable disease at 4 cycles and 1 had stable disease at 8 cycles. The median
      progression-free survival was 1.84 months. The common toxicities were rash,
      diarrhea, and liver enzyme elevations. Of the angiogenic cytokines evaluated,
      only the placental growth factor increased significantly with treatment (P <
      .0001). No pharmacodynamic parameters were associated with the treatment
      response. CONCLUSION: We report the results of a trial that combined cetuximab
      and sorafenib for the treatment of KRAS-mutated mCRC, with correlative imaging
      studies and pharmacodynamic angiogenic cytokine profiling as downstream markers
      of EGFR and VEGF receptor (VEGFR) signaling. No objective responses were
      observed. Additional development of biomarkers for patient selection is needed to
      evaluate combined EGFR and VEGFR blockade as a therapeutic option in KRAS-mutated
      CRC.

PMID- 25861839
TI  - Prospective evaluation of the aetiological profile of acute pancreatitis in young
      adult patients.
AB  - BACKGROUND: The aetiologies of acute pancreatitis in young adult patients are
      poorly known. AIMS: To prospectively evaluate the causes of acute pancreatitis in
      patients aged less than 35 years. METHODS: Overall, 309 consecutive patients
      admitted to our centre for acute pancreatitis received first-line investigations,
      including medical history, standard laboratory tests, abdominal ultrasound and
      computed tomography. If no aetiology was found, second-line investigations were
      performed, including endoscopic ultrasound, magnetic-resonance
      cholangiopancreatography and genetic testing in cases of idiopathic pancreatitis.
      RESULTS: Overall, 66 patients aged between 16 and 35 years were included. After
      first-line investigations, 49% of cases of acute pancreatitis remained
      idiopathic. Second-line investigations reduced this rate to 21%. The frequency of
      aetiologies for acute pancreatitis significantly differed in adults aged <= 35
      compared to those aged >35 years: biliary aetiology was less frequent (23% versus
      43%, p=0.003) as well as alcohol-related (8% versus 24%, p=0.01); drug-induced
      was more common (16% versus 4%, p=0.0007), as well as cannabis-related (13%
      versus 1%, p<0.0001), or genetic (10% versus 1.5%, p=0.003). CONCLUSIONS: The
      aetiologies of acute pancreatitis significantly differed in adults aged less than
      35 years when compared to older patients. Thus, use of medications, exposure to
      cannabis, and genetic mutations should be actively sought in these patients.

PMID- 25861840
TI  - Metronomic capecitabine as second-line treatment in hepatocellular carcinoma
      after sorafenib failure.
AB  - BACKGROUND: No standard second-line treatments are available for hepatocellular
      carcinoma patients who fail sorafenib therapy. We assessed the safety and
      efficacy of metronomic capecitabine after first-line sorafenib failure. METHODS:
      Retrospective analysis of consecutive hepatocellular carcinoma patients receiving
      metronomic capecitabine between January 2012 and November 2014. The primary end
      point was safety, secondary end-point was efficacy, including time-to-progression
      and overall survival. RESULTS: Twenty-six patients (80% Child-Pugh A, 80%
      Barcelona Clinic Liver Cancer stage C) received metronomic capecitabine (500
      mg/bid). Median treatment duration was 3.2 months (range 0.6-31). Fourteen (53%)
      patients experienced at least one adverse event. The most frequent drug-related
      adverse events were bilirubin elevation (23%), fatigue (15%), anaemia (11%),
      lymphoedema (11%), and hand-foot syndrome (7.6%). Treatment was interrupted in 19
      (73%) for disease progression, in 4 (15%) for liver deterioration, and in 1
      (3.8%) for adverse event. Disease control was achieved in 6 (23%) patients.
      Median time-to-progression was 4 months (95% confidence interval 3.2-4.7). Median
      overall survival was 8 months (95% confidence interval 3.7-12.3). CONCLUSIONS:
      Metronomic capecitabine was well tolerated in hepatocellular carcinoma patients
      who had been treated with sorafenib. Preliminary data show potential anti-tumour
      activity with long-lasting disease control in a subgroup of patients that
      warrants further evaluation in a phase III study.

PMID- 25861841
TI  - Prevalence of microalbuminuria in hypertensive patients with or without type 2
      diabetes in a Portuguese primary care setting: The RACE (micRoAlbumin sCreening
      survEy) study.
AB  - INTRODUCTION AND OBJECTIVES: To determine the prevalence of microalbuminuria
      (MAU) in outpatients with hypertension and/or type 2 diabetes mellitus (DM) and
      in normotensive, non-diabetic outpatients (control group); and, as secondary
      objectives, to examine the differences in the distribution of MAU in the four
      subgroups and the association of different clinical and epidemiological variables
      with MAU. METHODS: RACE (micRoAlbumin sCreening survEy) was a multicenter,
      descriptive observational cross-sectional study, which enrolled outpatients
      followed in primary care in Portugal. Patients with potential reasons for a false
      positive MAU test were excluded. The main outcome measures were the prevalence of
      MAU as assessed by Micral((r)) test strips and blood pressure. Demographic
      variables, presence of comorbidities, use of cardiovascular and antidiabetic
      drugs and biochemical variables were also analyzed. RESULTS: A total of 9198
      patients (3769 with hypertension, 3100 with both DM and hypertension, 423 with DM
      and without hypertension, and 1906 controls), 54.7% women, were included in the
      primary analysis. Overall prevalence of MAU was 58% in patients with DM and
      hypertension, 51% in patients with DM, 43% in patients with hypertension, and 12%
      in controls (chi-square: p<0.001 for all subgroups). In multivariate analysis,
      predictors for MAU were the presence of DM or hypertension, HbA1C, male gender,
      age, systolic blood pressure and total cholesterol. CONCLUSIONS: MAU is extremely
      common in outpatients with DM and/or hypertension followed in primary care,
      especially in those with both hypertension and DM and high cardiovascular risk.
      MAU screening would help identify individuals at risk and increase awareness of
      kidney disease and target organ damage.

PMID- 25861842
TI  - Alloantigen-specific CD4(+) regulatory T cells induced in vivo by ultraviolet
      irradiation after alloantigen immunization require interleukin-10 for their
      induction and activation, and flexibly mediate bystander immunosuppression of
      allograft rejection.
AB  - Ultraviolet (UV) irradiation prior to antigen immunization is employed to induce
      antigen-specific regulatory T cells (Tregs). UV-induced Tregs demonstrate unique
      bystander suppression, although antigen-specific activation is required
      initially. We previously reported the phenotype of alloantigen-specific
      transferable Tregs induced by UV-B irradiation after immunization was the same as
      T regulatory type 1-like CD4(+) T cells, with antigen-specific interleukin (IL)
      10 production. Here, by using semi-allogeneic transplantation models in vivo, we
      investigated the role of IL-10 in the induction and activation of these Tregs,
      and the possibility of bystander suppression of third-party allograft rejection.
      Naive mice (H-2(b)) were immunized with alloantigen (H-2(b/d)), and received UV-B
      irradiation (40 kJ/m(2)) 1 week later. Four weeks afterwards, splenic CD4(+) T
      cells were purified from the UV-irradiated immunized mice, and were transferred
      into naive mice (H-2(b)). Allografts expressing the same alloantigen as T-cell
      donors were immunized against (H-2(b/d)) or an irrelevant alloantigen (H-2(b/k))
      were transplanted to CD4(+) T-cell-transferred mice, and an alloantigen-specific
      prolongation of allograft survival observed. Experiments where IL-10 was
      neutralized by monoclonal antibody in the induction or effector phase revealed
      that IL-10 is critical, not only for induction but also for immunosuppressive
      function of CD4(+) Tregs induced by UV irradiation after alloantigen
      immunization. Third-party allografts (H-2(d/k)) were transplanted to CD4(+) T
      cell-transferred mice, and graft survival was also prolonged. Even a graft only
      partially compatible with immunized alloantigen worked well in vivo to activate
      CD4(+) Tregs induced by UV irradiation after alloantigen immunization, which
      resulted in the bystander suppression of third-party allograft rejection.

PMID- 25861843
TI  - The impact of ambient temperature on HbA1c in Taiwanese type 2 diabetic patients:
      The most vulnerable subgroup.
AB  - BACKGROUND/PURPOSE: The relationship between temperature variability and HbA1c
      has been reported in Caucasians, but not for Asians of Taiwanese origin. This
      study investigated the impact of temperature on HbA1c in various groups of
      Taiwanese with type 2 diabetes in Taiwan. METHODS: For this longitudinal follow
      up study which started in 2006, we recruited a total of 4399 patients with type 2
      diabetes who had been regularly followed up at Chi Mei Medical Center and
      obtained local temperature data for 2006 to 2011 from Taiwan's Central Weather
      Bureau. We used a generalized estimated equation (GEE) to analyze the HbA1c level
      and its change over time with temperature and temperature changes, respectively.
      RESULTS: We found a negative correlation between HbA1c and temperature (R = 
      0.475, p = 0.001). For every 1 degrees C decrement in temperature, there was an
      increase in the risk of having a HbA1c level >7% [p < 0.001, adjusted odds ratio
      (OR): 1.01]. There was a significantly higher risk of HbA1c > 7% among those in
      the lowest quartile of temperatures than the highest quartile (p = 0.0038,
      adjusted OR: 1.13). Patients with diabetic patients were at higher risk of HbA1C
      > 7% in the winter and spring than those in the summer (adjusted OR: 1.13, p =
      0.0027; adjusted OR: 1.14, p = 0.0022). After adjusting for various confounders,
      we found people who were younger than 65 years old, people who had diabetes for
      longer than 6 years, and people who had a body mass index (BMI) < 24 to be more
      susceptible to temperature changes (p = 0.0022, beta: 0.0095; p < 0.0001, beta:
      0.0125; p < 0.0001, beta: 0.016, respectively). CONCLUSION: Our study suggests
      cold weather may adversely affect HbA1c levels in Taiwanese people with type 2
      diabetes, especially in people under 65 years old, people with diabetes for
      longer than 6 years, and those with a BMI < 24.

PMID- 25861845
TI  - Chromogranin A in gastrinomas: Promises and pitfalls.
AB  - Patients with neuroendocrine tumors are found with increasing frequency.
      Accordingly, knowledge about relevant tumor markers and assays for diagnosis and
      control has become essential. Neuroendocrine tumors release one or more granin
      proteins. Of these, chromogranin A (CgA) has so far become the most widely used
      general marker. The CgA protein is, however, extensively cleaved and otherwise
      modified during the biosynthetic processing. In addition, the CgA-processing in
      individual tumors varies considerably. But only few CgA-assays have taken the
      processing into account and characterized the assays with respect to precise
      epitope-specificity. Consequently, we do not know which fragments most CgA-assays
      measure. It is therefore at present difficult to compare CgA-measurements from
      tumor patients. Some tumors, however, release - in addition to granins - also a
      specific hormone that causes a clinical syndrome. This review uses gastrinomas
      (gastrin-producing tumors) as a starting point for discussion of CgA versus
      peptide hormone as tumor marker. Data available so far indicate that well-defined
      assays for gastrin have significantly higher diagnostic sensitivity than CgA
      measurements in gastrinomas. But the review suggests that CgA-quantitation using
      processing-independent analysis (PIA) may provide an equally high diagnostic
      sensitivity and in addition offer a simple possibility for estimation of the
      tumor-burden. 

PMID- 25861844
TI  - Predictors for limb loss among patient with diabetic foot infections: an
      observational retrospective multicentric study in Turkey.
AB  - We aimed to investigate the predictors for limb loss among patients with diabetes
      who have complicated skin/soft-tissue infections. In this observational study,
      consecutive patients with diabetic foot infection (DFI) from 17 centres in
      Turkey, between May 2011 and May 2013 were included. The Turkish DFI Working
      Group performed the study. Predictors of limb loss were investigated by
      multivariate analysis. In total, 455 patients with DFI were included. Median age
      was 61 years, 68% were male, 65% of the patients were hospitalized, 52% of the
      patients had used antibiotics within the last month, and 121 (27%) had
      osteomyelitis. Of the 208 microorganisms isolated, 92 (44.2%) were Gram-positive
      cocci and 114 (54.8%) were Gram-negative rods (GNR). The most common GNR was
      Pseudomonas; the second was Escherichia coli, with extended spectrum beta
      lactamase positivity of 33%. Methicillin-resistant Staphylococcus species were
      found in 14% (29/208). Amputations were performed in 126/455 (28%) patients,
      44/126 (34%) of these were major amputations. In multivariate analysis,
      significant predictors for limb loss were, male gender (OR 1.75, 95% CI 1.04
      2.96, p 0.034), duration of diabetes >20 years (OR 1.9, 95% CI 1.18-3.11, p
      0.008), infected ulcer versus cellulitis (OR 1.9, 95% CI 1.11-3.18, p 0.019),
      history of peripheral vascular disease (OR 2, 95% CI 1.26-3.27, p 0.004),
      retinopathy (OR 2.25, 95% CI 1.19-4.25, p 0.012), erythrocyte sedimentation rate
      >70 mm/hr (OR 1.6, 95% CI 1.01-2.68, p 0.05), and infection with GNR (OR 1.8, 95%
      CI 1.08-3.02, p 0.02). Multivariate analysis revealed that, besides the known
      risk factors such as male gender, duration of diabetes >20 years, infected
      ulcers, history of peripheral vascular disease and retinopathy, detection of GNR
      was a significant predictor of limb loss. 

PMID- 25861846
TI  - Evaluation of the i-STAT point-of-care capillary whole blood hematocrit and
      hemoglobin: Comparison to the Siemens RAPIDLab 1200, Sysmex XE5000, and manual
      spun hematocrit.
AB  - BACKGROUND: Conductivity based point-of-care hematocrit with calculated
      hemoglobin devices serves an important role in clinical scenarios where time
      sensitive transfusion decisions are necessary. However, questions about the
      appropriateness of conductivity based assays in certain patient populations
      (patients on cardiopulmonary bypass and those receiving high volumes of
      intravenous fluids or autologous blood transfusions) have been raised. The
      clinical suitability of POC devices for these applications necessitates that they
      be accurate and that the results are interchangeable with central laboratory
      methods. METHODS: We performed hematocrit and hemoglobin analysis on 225 clinical
      samples using the i-STAT instrument, a standard reference method for hematocrit
      (manual spun) and other common methods on both cardiopulmonary bypass and non
      cardiopulmonary bypass patients. RESULTS: The i-STAT hematocrit and hemoglobin
      showed close agreement to comparison methods with minimal bias. Median test
      results were not clinically or statistically different between those measured on
      the i-STAT and those measured using the manual spun hematocrit reference method
      (p=0.4085, Wilcoxon signed rank test) or the Sysmex photometric hemoglobin method
      (p=0.2728, Wilcoxon signed rank test). The results on the i-STAT were
      statistically different from those obtained on the Sysmex for hematocrit
      (p<0.0001) and the Siemens RAPIDLab co-oximeter for hemoglobin (p<0.0001).
      CONCLUSION: The i-STAT hematocrit and hemoglobin performs well when compared to
      the hematocrit reference method and other common methods for both hematocrit and
      hemoglobin. Some differences between non-reference methods may be observed, but
      these were not considered clinically significant.

PMID- 25861847
TI  - Joint effects of serum uric acid and body mass index on risk of prehypertension
      in Chinese population.
AB  - BACKGROUND: There are few data available on the association between serum uric
      acid (UA) and prehypertension when hypertension prevention efforts may be
      applicable. METHODS: We performed a cross-sectional study to evaluate risk of
      prehypertension and its association with serum UA and other confounding factors.
      Levels of serum UA, blood pressure, body mass index (BMI) and some related
      factors were detected. RESULTS: Participants with prehypertension had higher
      levels of serum UA and BMI. Compared to those with normotension, the multivariate
      adjusted odds ratios [ORs, 95% confidence interval (CI)] for men with
      prehypertension were 1.33 (95% CI, 1.08-3.91) of serum UA and 1.21 (95% CI, 1.17
      1.29) of BMI. In women, the ORs were 1.96 (95% CI, 1.21-3.46) and 1.28 (95% CI,
      1.14-2.46), respectively. Increasing serum UA and BMI were associated with
      increased risk of prehypertension. Compared with the lowest quartiles, the
      highest serum UA and BMI quartiles entailed >4.4 times greater risk of
      prehypertension. In sex-specific analysis, OR was 2.41 (95% CI, 1.55-3.75) for
      men and 7.37 (95% CI, 4.16-13.0) for women. CONCLUSIONS: Both high serum UA and
      high BMI are associated with risk of prehypertension. Individuals with higher
      serum UA and BMI simultaneously have a higher risk for prehypertension,
      especially for women.

PMID- 25861848
TI  - Evaluation of hemoglobin A1c measurement by Capillarys 2 electrophoresis for
      detection of abnormal glucose tolerance in African immigrants to the United
      States.
AB  - BACKGROUND: Hemoglobin A1c (HbA1c) is used to monitor long-term glycemic control
      in individuals with diabetes, guide therapy, predict the risk of microvascular
      complications, and more recently to diagnose diabetes. An automated liquid-flow
      capillary electrophoresis method was recently developed to measure HbA1c using
      the Capillarys 2 Flex Piercing instrument. METHODS: Analytical evaluation was
      performed at 2 clinical centers. A clinical analysis was conducted in 109 African
      born individuals, 24% of whom have variant hemoglobin (HbAS or HbAC). Abnormal
      glucose tolerance (which includes both diabetes and prediabetes) was defined as
      2h glucose of >= 140 mg/dl (7.8 mmol/l) during an oral glucose tolerance test.
      RESULTS: Interlaboratory CVs were <= 2.1%. The method showed satisfactory
      correlation with 2 other analyzers that measure HbA1c by high-performance liquid
      chromatography. Neither labile HbA1c, carbamylated hemoglobin, uremia, bilirubin
      nor common hemoglobin variants (HbC/HbS/HbE) interfered. Forty-five individuals
      (41%) had abnormal glucose tolerance. The sensitivity of HbA1c for diagnosing
      abnormal glucose tolerance was 38%, 36% and 42% for total, normal and variant
      hemoglobin groups, respectively. CONCLUSIONS: The analytical performance of HbA1c
      on the Capillarys 2 is suitable for clinical application. Variant hemoglobin in
      Africans did not interfere with the detection of abnormal glucose tolerance by
      HbA1c measured on the Capillarys 2.

PMID- 25861849
TI  - Establishment of a novel lectin-antibody ELISA system to determine core
      fucosylated haptoglobin.
AB  - BACKGROUND: Fucosylated haptoglobin (Fuc-Hpt) is a novel cancer biomarker that
      increases in various pathological conditions. We previously established a Fuc-Hpt
      lectin-antibody assay using Aleuria aurantia lectin (AAL), and applied this to
      diagnose several diseases, including various cancers. AAL recognizes both alpha1
      3/1-4 and alpha1-6 fucosylation on N/O-linked glycans. These fucosylation types
      differ in biological function, and in regulation by different
      fucosyltransferases. Recently, we identified a novel lectin, Pholiota squarrosa
      lectin (PhoSL), which specifically recognizes alpha1-6 fucosylation (core
      fucosylation). METHODS: We developed a lectin-antibody ELISA kit using PhoSL to
      determine core-Fuc-Hpt levels in sera from colorectal or pancreatic cancer
      patients. RESULTS: Serum levels of AAL-reactive Hpt are higher in pancreatic
      cancer patients, whereas those of PhoSL-reactive Hpt are higher in colorectal
      cancer patients. Mass spectrometry analyses of Hpt fucosylation levels were
      consistent with lectin-antibody ELISA results. Hpt-transfected colorectal cancer
      cell lines produced significant amounts of core-Fuc-Hpt, suggesting that
      colorectal cancer tissues produce core-Fuc-Hpt. CONCLUSIONS: These differences in
      Fuc-Hpt patterns might depend on cancer cells and the surrounding cells, which
      produce Hpt.

PMID- 25861850
TI  - In vivo administration of the frog skin peptide frenatin 2.1S induces
      immunostimulatory phenotypes of mouse mononuclear cells.
AB  - Host-defense peptides secreted by epithelial cells exhibit cytotoxic and
      immunoregulatory effects in order to protect the organism against invading
      microorganisms. Antimicrobial peptides derived from frog skin display both
      immunostimulatory and immunosuppressive actions as demonstrated by in vitro
      cytokine production by macrophages. Frenatin 2.1S, first isolated from skin
      secretions of the frog, Sphaenorhynchus lacteus (Hylidae), enhances the in vitro
      production of pro-inflammatory IL-1beta, TNF-alpha and IL-23 by mouse peritoneal
      cells. In order to test whether the immunostimulatory action of frenatin 2.1S may
      be reproduced in vivo, effects of intraperitoneal injections of this peptide on
      mononuclear cells in the peritoneum and spleen were determined 24h after
      administration. The data indicate that frenatin 2.1S enhances the activation
      state and homing capacity of Th1 type lymphocytes and NKT cells in the mouse
      peritoneal cavity, as evaluated by increased expression of early activation
      marker CD69 among T and NKT cells and chemokine receptor CXCR3 among T cells.
      Frenatin 2.1S significantly increases the percentage of
      (F4/80(+)CD11c(+)CD206(+)) pro-inflammatory M1 macrophages and enhances the
      expression of MHC class II molecules on F4/80(+)CD11c(+) macrophages in the mouse
      peritoneal cavity. Additionally, injection of frenatin 2.1S, in the presence or
      absence of lipopolysaccharide, increases the percentage of peritoneal B cells of
      the (CD19(+)CD11b(+)CD5(+)) B1a phenotype thus contributing to an inflammatory
      milieu. We suggest that the immunostimulatory effect of frenatin 2.1S may have
      therapeutic relevance in disease states, such as certain types of cancer, in
      which an enhanced inflammatory response may be beneficial. 

PMID- 25861851
TI  - Arthroscopically assisted elbow interposition arthroplasty without hinged
      external fixation: surgical technique and patient outcomes.
AB  - BACKGROUND: Total elbow arthroplasty is successful in older, lower demand
      patients but not in the younger, more active individual with severe elbow
      arthritis. Interposition arthroplasty is an alternative for younger patients who
      hope to minimize the degree to which arm use is restricted. Interposition
      arthroplasty traditionally involves release of all ligaments and capsule. As a
      result, the postoperative care included the use of a hinged external fixator of
      the elbow to apply distraction and to permit motion during the early phases of
      healing. We describe a novel surgical technique without a hinged external fixator
      that allows secure fixation of the interposition graft through arthroscopic
      assistance and maintains the integrity of the medial collateral ligament with
      only a takedown and repair of the lateral collateral ligament complex. METHODS: A
      retrospective chart review was performed to analyze 4 patients with an average
      age of 57 years who underwent surgery between 2007 and 2011. The patients were
      also contacted to assess elbow-specific American Shoulder and Elbow Surgeons and
      Disabilities of the Arm, Shoulder, and Hand scores. RESULTS: The average follow
      up was 3.6 years (range, 2.5-6 years), and 1 patient was converted to a total
      elbow arthroplasty after 2.5 years because of persistent pain. The remaining 3
      patients have done well with regard to pain control, stability, and functional
      use of the operative extremity. There were no postoperative complications.
      DISCUSSION: On the basis of our small series of patients, an arthroscopically
      assisted elbow interposition arthroplasty without hinged external fixation can
      provide satisfactory medium-term outcomes as a salvage procedure for a difficult
      condition with limited options.

PMID- 25861852
TI  - Endobutton versus transosseous suture repair of distal biceps rupture using the
      two-incision technique: a comparison series.
AB  - BACKGROUND: The purpose of this study was to report the outcome of a large cohort
      of patients undergoing distal biceps tendon repair. We compared the endobutton
      and transosseous suture repair techniques, both performed through a 2-incision
      approach. METHOD: At an average of 2.1 years after a distal biceps repair, 46
      male patients (19 endobutton and 27 transosseous suture) were reviewed. The mean
      age of our patients was 50 years. RESULTS: Forty-three patients (93%) were
      satisfied with the results of their distal biceps tendon repair. The average pain
      score was 1.3 of 10 at a mean 2.1 years after repair. More than 80% of patients
      had regained their premorbid function in both recreational and occupational
      activities. The mean Mayo Elbow Performance Score was 93 of 100. Biodex strength
      testing demonstrated restoration of 92% of low-velocity supination power, 102% of
      high-velocity supination power, and 104% endurance compared with the
      contralateral limb. There was no statistically significant difference in
      postoperative strength between the transosseous suture and endobutton groups.
      There were 3 complications in this series, 1 case of heterotopic ossification and
      2 cases of injury to the lateral cutaneous nerve of the forearm. CONCLUSION: In
      this large cohort of 2-incision distal biceps repairs, we found a high degree of
      patient satisfaction and a low complication rate. We did not find any difference
      in clinical outcome with regard to subjective patient rating, pain, range of
      motion, or supination strength when comparing the 2-incision endobutton and
      transosseous suture fixation techniques.

PMID- 25861853
TI  - The effect of proximal humeral bone loss on revision reverse total shoulder
      arthroplasty.
AB  - BACKGROUND: Revision shoulder arthroplasty can be complicated by osseous and soft
      tissue deficiencies. Proximal humeral bone loss can result in diminished implant
      stability and reduced functional outcomes, and some studies have advocated the
      use of humeral allograft in this setting. This study compares the outcomes of
      revision reverse total shoulder arthroplasty (RTSA) in patients both with and
      without proximal humeral bone loss. METHODS: During a 6-year period, 32 patients
      were revised to RTSA for failed shoulder hemiarthroplasty. Proximal humeral bone
      loss was found in 16 patients, with an average loss of 36.3 mm (range, 17.2-66
      mm). Patients were followed up an average of 51.2 months with the American
      Shoulder and Elbow Surgeons score, Simple Shoulder Test score, visual analog
      scale score for pain, subjective outcome ratings, and radiographs. RESULTS:
      Significant improvement was found for average American Shoulder and Elbow
      Surgeons score (30.7 to 66.8), Simple Shoulder Test score (1.6 to 5.3), visual
      analog scale score (6.0 to 2.6), and forward flexion (51 degrees  to 100 degrees
      ) but not for external rotation (15 degrees  to 19.1 degrees ). No difference was
      demonstrated for functional or subjective outcomes compared with patients with
      intact humeral bone, except for active motion. On radiographic examination, 3
      patients demonstrated humeral-sided loosening. Five complications were noted in
      patients with humeral bone loss. CONCLUSION: Revision RTSA can provide successful
      outcomes in the presence of proximal humeral bone loss without the use of
      allograft. Implant stability may be improved by the use of a cemented long-stem
      monoblock humeral prosthesis in revision settings.

PMID- 25861854
TI  - Radial clubhand with congenital absence of elbow flexors treated by pedicled
      latissimus dorsi bipolar transfer: report of one case.

PMID- 25861855
TI  - Deep brain stimulation for psychiatric disorders: Are nucleus accumbens and
      medial forebrain bundle two branches of the same tree?
AB  - Purpose of this commentary is to discuss the relation of the nucleus accumbens
      (NA) with the medial forebrain bundle (MFB) and compare them as deep brain
      stimulation (DBS) targets in psychiatric disorders. Could a "bundle" be a more
      effective target than a "nucleus"? Or, more correctly, could an important
      "modulator" be a more effective target than a highly significant "pleasure
      center"? The answer hides in the fact that NA is a key component of the MFB. Thus
      NA dysfunction is synonym to MFB dysfunction. The NA is a "hot-spot" in the
      neurocircuitry of psychiatric disorders and further experimental investigation is
      needed for the MFB as a target for neuromodulation in depression, as well as to
      optimize benefit of psychiatric patients from neuromodulation treatment efforts.
      Are the NA and MFB two branches of the same tree? They definitely could be,
      particularly if the "tree" is the brain's "motivation super-system". 

PMID- 25861856
TI  - [Robson classification: A tool for assessment of caesarean practices in France].
AB  - OBJECTIVE: To give a description of caesarean rates in France in 2010 using
      Robson classification, to assess practices according to the level of care of the
      maternity units. MATERIALS AND METHODS: The study population was the sample of
      the French National Perinatal Survey in 2010 (n=14,165). Data were stratified by
      the level of care of the maternity unit (1, 2 or 3). Women were classified in 12
      groups according to Robson classification, using maternal characteristics and
      obstetrical history. In each level of care, we calculated for each group, its
      relative size, its crude caesarean rate and its contribution to the overall
      caesarean rate. RESULTS: The overall rate of caesarean in 2010 in France was
      20.8% in level 1, 21.1% in level 2 and 20.0% in level 3 maternity units. In the
      three levels, the main contributors to the overall caesarean rate were
      primiparous women in spontaneous labour (group 1; contribution: 3.5% in level 1
      units, 2.2% in level 2 units, 2.7% in level 3 units) or with induced labour
      (group 2a; contribution: 2.9, 2.5 and 3.0%, respectively) and multiparous women
      with previous caesarean (group 5; contribution: 5.8, 5.3 and 6.0%, respectively).
      Premature singletons (group 10) contributed to 0.8% to the overall caesarean rate
      in level 1 units, 1.4% in level 2 units and 3.5% in level 3 units. CONCLUSION:
      The Robson classification is easy to use. Each maternity unit can compare its
      rates with those of units with similar level, to find whether some groups of
      women have very high rates of caesarean sections.

PMID- 25861857
TI  - Improvement of cardiac screening in amateur athletes.
AB  - Although not performing on a professional level, amateur athletes, nevertheless,
      are participating in competitive sports and thus underlie a relevant risk for
      exercise-related SCD which implicates the need for an adequate pre-competition
      cardiac screening. As many amateur athletes belong to the category of "older"
      individuals, particularly CAD among male athletes with risk factors has to be
      targeted by the screening. However, the detection of clinically silent underlying
      coronary heart disease is challenging and cannot be accurately achieved by a
      standard screening provided to young athletes (history, clinical status, ECG). An
      extended work-up, at least, mandates the detection of cholesterol levels to
      estimate the individual cardiovascular risk. The fact that only less than 10% of
      Swiss amateur athletes have undergone cardiac screening led to various promising
      approaches to improve the awareness of the issue. Exemplarily, we successfully
      invented an "on-site" prevention campaign that positively influenced the attitude
      of the athletes towards cardiac screening.

PMID- 25861858
TI  - Introduction: Genomics and philosophy of race.

PMID- 25861859
TI  - Going the whole orang: Darwin, Wallace and the natural history of orangutans.
AB  - This article surveys the European discovery and early ideas about orangutans
      followed by the contrasting experiences with these animals of the co-founders of
      evolution by natural selection, Charles Darwin and Alfred Russel Wallace. The
      first non-human great ape that both of them interacted with was the orangutan.
      They were both profoundly influenced by what they saw, but the contexts of their
      observations could hardly be more different. Darwin met orangutans in the
      Zoological Gardens in London while Wallace saw them in the wild in Borneo. In
      different ways these observations helped shape their views of human evolution and
      humanity's place in nature. Their findings played a major role in shaping some of
      the key questions that were pursued in human evolutionary studies during the rest
      of the nineteenth century. 

PMID- 25861860
TI  - Selective inhibitors of Plasmodium falciparum glycogen synthase-3 (PfGSK-3): New
      antimalarial agents?
AB  - Plasmodium falciparum glycogen synthase kinase-3 (PfGSK-3) is one of the
      eukaryotic protein kinases that were identified as essential for the parasite
      causing malaria tropica. Although the physiological functions of PfGSK-3 are
      still unknown, it had been suggested as a putative target for novel antimalarial
      drugs. The high structural similarity of PfGSK-3 and its human orthologue HsGSK-3
      makes the development of selective PfGSK-3 inhibitors a challenging task.
      Actually, established GSK-3 inhibitors are either unselective or are more potent
      for inhibition of the mammalian GSK-3. A high throughput screening campaign
      identified thieno[2,3-b]pyridines as a new class of PfGSK-3 inhibitors.
      Systematic variation of the substitution pattern at the parent scaffold led to
      compounds which selectively inhibited the plasmodial enzyme. These compounds also
      exhibited activity against erythrocyte stages of the parasites. A hypothetical
      explanation for the selectivity of the new antimalarial compounds was enunciated
      based on the results of docking a selective inhibitor into a PfGSK-3 homology
      model and by comparison of the results with an X-ray structure of HsGSK-3 co
      crystallized with a similar but unselective compound. This article is part of a
      Special Issue entitled: Inhibitors of Protein Kinases. 

PMID- 25861861
TI  - Perspective on computational and structural aspects of kinase discovery from
      IPK2014.
AB  - Recent advances in understanding the activity and selectivity of kinase
      inhibitors and their relationships to protein structure are presented.
      Conformational selection in kinases is studied from empirical, data-driven and
      simulation approaches. Ligand binding and its affinity are, in many cases,
      determined by the predetermined active and inactive conformation of kinases.
      Binding affinity and selectivity predictions highlight the current state of the
      art and advances in computational chemistry as it applies to kinase inhibitor
      discovery. Kinome wide inhibitor profiling and cell panel profiling lead to a
      better understanding of selectivity and allow for target validation and patient
      tailoring hypotheses. This article is part of a Special Issue entitled:
      Inhibitors of Protein Kinases. 

PMID- 25861862
TI  - Flooding modifies the genotoxic effects of pollution on a worm, a mussel and two
      fish species from the Sava River.
AB  - Extreme hydrological events, such as water scarcity and flooding, can modify the
      effect of other stressors present in aquatic environment, which could result in
      the significant changes in the ecosystem functioning. Presence and interaction of
      various stressors (genotoxic pollutants) in the environment can influence the
      integrity of DNA molecules in aquatic organisms which can be negatively reflected
      on the individual, population and community levels. Therefore, in this study we
      have investigated the impact of flooding, in terms of genotoxicity, on organisms
      belonging to different trophic levels. The study was carried out on the site
      situated in the lower stretch of the Sava River which faced devastating effects
      of severe flooding in May 2014. The flooding occurred during our field experiment
      and this event provided a unique opportunity to assess its influence to the
      environment. The in situ effects of this specific situation were monitored by
      measuring physical, chemical and microbiological parameters of water, and by
      comparing the level of DNA damage in coelomocytes and haemocytes of freshwater
      worms Branchiura sowerbyi, haemocytes of freshwater mussels Unio tumidus and
      blood cells of freshwater fish Abramis bjoerkna/Abramis sapa, by means of the
      comet assay. Our study indicated that the flooding had a significant impact on
      water quality by decreasing the amount and discharge rate of urban wastewaters
      but simultaneously introducing contaminants from the nearby fly ash disposal
      field into river by runoff, which had diverse effects on the level of DNA damage
      in the studied organisms. This indicates that the assessment of genotoxic
      pollution in situ is strongly affected by the choice of the bioindicator
      organism. 

PMID- 25861863
TI  - For a better morpho-dynamic evaluation of the portal system in cirrhosis.

PMID- 25861864
TI  - The endless SEARCH for a better medical treatment of advanced hepatocellular
      carcinoma.

PMID- 25861865
TI  - Polymorphism in mature microRNA-608 sequence is associated with an increased risk
      of nasopharyngeal carcinoma.
AB  - Accumulative evidences indicated that microRNAs (miRNAs) can function as tumor
      suppressors and oncogenes, in which genetic variations are implicated in various
      cancer susceptibilities. However, it remains unclear whether single nucleotide
      polymorphisms (SNPs) in mature miRNA sequence alter nasopharyngeal carcinoma
      (NPC) susceptibility. In this study, we analyzed associations between eight SNPs
      in miRNA mature sequences (i.e., rs3746444T>C in hsa-mir-499, rs4919510C>G in hsa
      mir-608, rs13299349G>A in hsa-mir-3152, rs12220909G>C in hsa-mir-4293,
      rs2168518G>A in hsa-mir-4513, rs8078913T>C in hsa-mir-4520a, rs11237828T>C in hsa
      mir-5579, and rs9295535T>C in hsa-mir-5689) and NPC susceptibility in southern
      China with 906 NPC cases and 1072 cancer-free controls, and validated the
      significant findings in eastern China with 684 cases and 907 healthy controls.
      Functional assays were further performed to identify the biological effects of
      these polymorphisms. We found that rs4919510C>G polymorphism showed a consistent
      association with NPC risk in southern China (GC+GG versus CC genotype, odds ratio
      [OR]=1.36, 95% confidence interval [CI]=1.10-1.70) and eastern China (GC+GG
      versus CC: OR=1.37, 95% CI=1.08-1.74). After the two populations were merged, the
      ORs and 95% CI were 1.38 and 1.18 to 1.62, respectively. Moreover, the
      rs4919510C>G adverse genotypes significantly interacted with Epstein-Barr virus
      (EBV) infection on increasing NPC risk (P=0.001). The functional assay further
      showed that the CNE-2 cell lines that transfected with miR-608-rs4919510G allele
      expression vector exerted more colony number formations than cell lines that
      transfected with miR-608-rs4919510C allele expression vector (P=0.001). These
      data suggested that rs4919510C>G of miR-608 may be a susceptible biomarker of NPC
      in China.

PMID- 25861867
TI  - Glutamate synthase: A case-study for in silico drug screening on a complex iron
      sulfur flavoenzyme?

PMID- 25861866
TI  - Estimated carrier frequency of creatine transporter deficiency in females in the
      general population using functional characterization of novel missense variants
      in the SLC6A8 gene.
AB  - Creatine transporter deficiency (CRTR-D) is an X-linked inherited disorder of
      creatine transport. All males and about 50% of females have intellectual
      disability or cognitive dysfunction. Creatine deficiency on brain proton magnetic
      resonance spectroscopy and elevated urinary creatine to creatinine ratio are
      important biomarkers. Mutations in the SLC6A8 gene occur de novo in 30% of males.
      Despite reports of high prevalence of CRTR-D in males with intellectual
      disability, there are no true prevalence studies in the general population. To
      determine carrier frequency of CRTR-D in the general population we studied the
      variants in the SLC6A8 gene reported in the Exome Variant Server database and
      performed functional characterization of missense variants. We also analyzed
      synonymous and intronic variants for their predicted pathogenicity using in
      silico analysis tools. Nine missense variants were functionally analyzed using
      transient transfection by site-directed mutagenesis with In-Fusion HD Cloning in
      HeLa cells. Creatine uptake was measured by liquid chromatography tandem mass
      spectrometry for creatine measurement. The c.1654G>T (p.Val552Leu) variant showed
      low residual creatine uptake activity of 35% of wild type transfected HeLa cells
      and was classified as pathogenic. Three variants (c.808G>A; p.Val270Met,
      c.942C>G; p.Phe314Leu and c.952G>A; p.Ala318Thr) were predicted to be pathogenic
      based on in silico analysis, but proved to be non-pathogenic by our functional
      analysis. The estimated carrier frequency of CRTR-D was 0.024% in females in the
      general population. We recommend functional studies for all novel missense
      variants by transient transfection followed by creatine uptake measurement by
      liquid chromatography tandem mass spectrometry as fast and cost effective method
      for the functional analysis of missense variants in the SLC6A8 gene. 

PMID- 25861868
TI  - Characterization of two paralogous myostatin genes and evidence for positive
      selection in Tibet fish: Gymnocypris przewalskii.
AB  - Myostatin (mstn) is an important member of TGF-beta superfamily, a muscle growth
      inhibitor. Though mstn has been identified in many organisms, little is known
      about this gene in highland fish, Gymnocypris przewalskii endemic to the Qinghai
      Tibetan Plateau. In this study, we first cloned two paralogous mstn genes (mstn1
      and mstn2) from G. przewalskii through homologue cloning. The 3D structures of
      both Mstn proteins varied in the numbers of beta-sheets and conformations of
      alpha-helices. The branch-site model showed that mstn1 has undergone positive
      selection, and two positively selected sites (107M and 181T) were located on the
      random coils of the 3D protein structure. Expression patterns indicated that the
      mstn1 expressed widely, while the mstn2 only expressed in the muscle and brain.
      During the early stage of embryo development, the expression levels of both mstn
      paralogous genes showed different increasing trends. These results suggest that
      it is diverging in two mstn paralogues of G. przewalskii via specific differences
      in gene structure, protein structure, selection pressure and gene expression
      patterns. Taken together, this study provides novel contribution on the research
      topics of growth related gene function and mechanism of highland fish in extreme
      aquatic environment on the Qinghai-Tibetan Plateau. 

PMID- 25861869
TI  - Thermostable chitinase II from Thermomyces lanuginosus SSBP: Cloning, structure
      prediction and molecular dynamics simulations.
AB  - Thermomyces lanuginosus is a thermophilic fungus that produces large number of
      industrially-significant enzymes owing to their inherent stability at high
      temperatures and wide range of pH optima, including thermostable chitinases that
      have not been fully characterized. Here, we report cloning, characterization and
      structure prediction of a gene encoding thermostable chitinase II. Sequence
      analysis revealed that chitinase II gene encodes a 343 amino acid protein of
      molecular weight 36.65kDa. Our study reports that chitinase II exhibits a well
      defined TIM-barrel topology with an eight-stranded alpha/beta domain. Structural
      analysis and molecular docking studies suggested that Glu176 is essential for
      enzyme activity. Folding studies of chitinase II using molecular dynamics
      simulations clearly demonstrated that the stability of the protein was evenly
      distributed at 350K. 

PMID- 25861870
TI  - Adaptive dynamics on an environmental gradient that changes over a geological
      time-scale.
AB  - The standard adaptive dynamics framework assumes two timescales, i.e. fast
      population dynamics and slow evolutionary dynamics. We further assume a third
      timescale, which is even slower than the evolutionary timescale. We call this the
      geological timescale and we assume that slow climatic change occurs within this
      timescale. We study the evolution of our model population over this very slow
      geological timescale with bifurcation plots of the standard adaptive dynamics
      framework. The bifurcation parameter being varied describes the abiotic
      environment that changes over the geological timescale. We construct evolutionary
      trees over the geological timescale and observe both gradual phenotypic evolution
      and punctuated branching events. We concur with the established notion that
      branching of a monomorphic population on an environmental gradient only happens
      when the gradient is not too shallow and not too steep. However, we show that
      evolution within the habitat can produce polymorphic populations that inhabit
      steep gradients. What is necessary is that the environmental gradient at some
      point in time is such that the initial branching of the monomorphic population
      can occur. We also find that phenotypes adapted to environments in the middle of
      the existing environmental range are more likely to branch than phenotypes
      adapted to extreme environments. 

PMID- 25861871
TI  - The Decision Making Ecology of placing a child into foster care: A structural
      equation model.
AB  - The Decision Making Ecology provided a framework for empirically testing the
      impact of Case, Caseworker and Organizational factors on the decision to place
      children in out-of-home care. The structural equation model we developed fit the
      data extremely well, indicating a complex relationship between the variables. The
      main findings indicate that Case factors, even as aggregated to the worker level,
      were of most importance: Percent Removed was increased in part by greater average
      Risk being assessed and more families on a worker's caseload being Low Income.
      Furthermore, removal rates were increased by lower proportions of Hispanic
      families on the caseload, as well as lower organizational support, and a
      perception of manageable workload and sufficient resources. Individual factors,
      i.e., variables characterizing the caseworkers themselves, were not found to
      directly influence the placement decision, including workers' own race/ethnicity,
      though various orders of mediated effects were indicated, and these are detailed.
      Interrelationships between variables that affect case, caseworker and
      organizational factors are discussed along with implications for practice. 

PMID- 25861872
TI  - Prevalence and characterization of hybrid blaCTX-M among Escherichia coli
      isolates from livestock and other animals.
AB  - This study investigated 248 extended-spectrum beta-lactamase-producing
      Escherichia coli isolates from 2012 to 2013 for hybrid blaCTX-M genes. blaCTX-M
      genes were detected in 228 isolates of which 14 isolates were hybrid blaCTX-M
      positive (6 blaCTX-M-123, 6 blaCTX-M-64, and 2 blaCTX-M-132). The 14 hybrid
      blaCTX-M-carrying isolates (8 from chickens, 2 each from pigs and cattle, 1 each
      from dog and rodent) were genetically diverse. All but 2 hybrid blaCTX-M were
      carried on IncI1 (5 blaCTX-M-123) and IncI2 (6 blaCTX-M-64 and one blaCTX-M-132)
      plasmids. Our IncI1 and IncI2 plasmids had pHNAH4-1-like and pHN1122-1-like
      restriction fragment length polymorphism patterns, respectively. Genetic
      relatedness of the plasmids to pHNAH4-1 and pHN1122-1 were confirmed by complete
      sequencing of 3 plasmids, pCTXM123_C0996, pCTXM64_C0967, and pCTXM132_P0421.
      Plasmids closely related to pHNAH4-1 and pHN1122-1 and carrying different blaCTX
      M alleles have been reported from multiple geographic areas in China previously.
      The findings highlighted the wide dissemination of hybrid blaCTX-M variants in
      different parts of China. 

PMID- 25861873
TI  - Comparison of a quantitative PCR assay with peripheral blood smear examination
      for detection and quantitation of Babesia microti infection in humans.
AB  - Using a real-time quantitative PCR (qPCR), we determined the number of DNA
      copies/mL of blood of a Babesia microti gene in infected patients. Thirty-six
      patients (whose median age was 62.5years and 75.0% were male) with at least 1
      qPCR-positive blood sample were included in this analysis, including 16 with
      serial blood samples. Based on testing of serial blood samples, it could be
      demonstrated that the smear became negative while the qPCR remained positive. A
      moderate to strong correlation was found between the DNA copy number and the
      number of infected erythrocytes per milliliter of blood (Pearson's r=0.68,
      P<0.001). Based on limited data, the DNA copy number fell by a mean of 4.1-12.9%
      per day on active treatment and by 3.5-7.1% per day off therapy. qPCR methodology
      may permit systematic evaluations of the relative efficacy of various
      antiparasitic drug regimens and other therapeutic modalities, although a
      limitation of such testing is that DNA detection per se does not establish the
      presence of viable parasites. 

PMID- 25861874
TI  - The evolving role of MDCT in the assessment of patients with chronic obstructive
      pulmonary disease.
AB  - The purpose of this article is to educate the reader in the value a radiologist
      can offer in the multidetector (MD) CT assessment of patients with chronic
      obstructive pulmonary disease (COPD). MDCT can identify patients in whom
      treatments such as lung volume reduction surgery or newer endobronchial therapies
      may be of benefit. We will also discuss important and under-recognised associated
      cardiorespiratory disease, which may be incidentally identified. 

PMID- 25861875
TI  - Neuromyelitis optica spectrum disorders: beyond longitudinally extensive
      transverse myelitis.
AB  - AIM: To describe the neuroradiological features and their prevalence in patients
      with neuromyelitis optica (NMO). MATERIALS AND METHODS: Two neuroradiologists
      independently reviewed 35 spinal cord and 37 brain MRI studies from patients with
      NMO. The examinations were analysed for the presence of lesion, topography,
      enhancement, and brain lesions suggestive of multiple sclerosis and/or NMO.
      RESULTS: Seventy percent of the spinal cord lesions involved over three or more
      vertebral segments. Seventy-eight percent of brain scans were abnormal, and the
      most prevalent findings were non-specific foci of T2 hyperintensities in the
      cerebral white matter (55%) and brainstem lesions (52%). One patient had lesions
      disseminated in space compatible with multiple sclerosis according to 2010
      revised McDonald criteria. Brain lesions suggestive of NMO occurred at least once
      in 17 (59%) patients. CONCLUSION: Spinal cord lesions were often longitudinally
      extensive and brain lesions were common, with the majority of patients having at
      least one distinctive NMO lesion.

PMID- 25861876
TI  - Investing in future pediatric subspecialists: a fellowship curriculum that
      prepares for the transition to academic careers.
AB  - BACKGROUND: The experience of transitioning to an academic faculty position can
      be improved with standardized educational interventions. Although a number of
      such interventions have been described, few utilize an evaluation framework,
      describe a robust evaluation process, and address why their interventions were
      successful. In this article, the authors apply a logic model to describe their
      efforts to develop, implement, evaluate, and revise a comprehensive academic
      career development curriculum among pediatric subspecialty fellows. They describe
      inputs, activities, outputs, and outcomes using quantitative data from fellow
      evaluations and qualitative data from faculty interviews. METHODS: Methods are
      described under the input and activities sections. The curriculum started with
      collaboration among educational leadership and conducting a needs assessment.
      Using the needs assessment results and targeted learning objectives, we piloted
      the curriculum and then implemented the full curriculum 1 year later. RESULTS:
      Results are described under the outputs and outcomes sections. We present
      immediate, short-term, and 6-month evaluation data. Cumulative data over 3 years
      reveal that fellows consistently acquired knowledge relevant to transitioning and
      that they applied acquired knowledge to prepare for finding jobs and career
      advancement. The curriculum also benefits faculty instructors who gain a sense of
      reward by filling a critical knowledge gap and fostering fellows' professional
      growth. CONCLUSION: The authors relate the success and effectiveness of the
      curriculum to principles of adult learning, and share lessons learned, including
      the importance of buy-in from junior and senior fellows and faculty,
      collaboration, and designating the time to teach and learn.

PMID- 25861877
TI  - Clinical findings in a multi-ethnic adult hepatitis B virus patient population in
      Denmark with emphasis on genotypic characteristics.
AB  - OBJECTIVE: Most knowledge about chronic hepatitis B virus (HBV) infection is
      based upon studies in high-endemic areas with one or two predominant genotype(s).
      The aim of the study was to describe clinical characteristics of a heterogeneous
      genotypic HBV patient population in a low-endemic European country. METHODS: Data
      from HBV patients currently followed in a Danish university hospital and
      affiliated regional clinics were reviewed in accordance to genotype status.
      RESULTS: Of 540 HBV patients, 462 (86%) were of non-Danish ethnicity originating
      from 43 different countries. HBV genotype was known in 37% of the patients: A
      (11%), B (25%), C (25%), D (37%) and E (2%). Logistic regression analysis of pre
      treatment data among genotype A-D patients receiving nucleos(t)ide analogue (NA)
      therapy revealed a decreased HBeAg rate by age (OR = 0.93; CI: 0.89-0.97; p <
      0.01) and an increased rate in genotype C patients (OR = 20.5; CI: 3.3-129; p <
      0.01). Among untreated patients HBeAg rate was also significantly decreased by
      age (OR = 0.90 (0.85:0.95; p < 0.0001), whereas the rate was increased in both
      genotype B and C patients (OR = 7.5; CI: 1.8-30.5; p < 0.01 and OR = 12.2; CI:
      3.2-46.6; p < 0.001, respectively). No significant variation was found in HBV DNA
      level in any of the two groups when adjusting for age, gender, genotype and
      HBeAg. Increased liver pathology prevalence was, irrespectively of treatment
      status, associated to age and male gender, but not to any genotype. CONCLUSION:
      In this study population, genotype B and C was found associated with higher HBeAg
      rate but not with increased liver pathology.

PMID- 25861878
TI  - The relationship of vocal tract dimensions and substitution of the palatal
      approximant /j/ for the alveolar trill /r/.
AB  - PURPOSE: To investigate the relationship of the vocal tract dimensions and dental
      arches in participants with substitution of palatal approximant /j/ for the trill
      variant of /r/. METHOD: Cephalograms and dental casts of 60 native speakers of
      Arabic were used for comparison. The experimental group included 30 participants
      with substitution of /j/ for the trill variant of /r/ (17 males and 13 females,
      age ranged between 15-20 years, M = 18.7 years, SD = 1.27). The control group
      included 30 normal speakers (15 males and 15 females, age ranged between 15-20
      years, M = 18.3 years, SD = 1.67). Both groups had class I occlusion. RESULT: The
      experimental group showed significantly shorter maxillary length, p < 0.05, and
      narrower vocal tract dimensions compared to the control group, p < 0.05. Tongue
      length (TGL) and height (TGH) and soft palate length (PNSP) and thickness (MPT)
      were statistically significantly reduced in the experimental group compared to
      the control group, p < 0.05. The distance between the hyoid bone and
      retrognathion or C3 was significantly shorter in the experimental group compared
      to the control group, p < 0.05. Inter-canine widths and dental arch lengths were
      significantly shorter in the experimental group compared to the control group, p
      < 0.05. CONCLUSION: The substitution of /j/ for the trill variant of /r/ is
      associated with altered dimensions of the vocal tract. These alterations may
      explain the residual articulation disorder during the production of the trilled
      /r/ compared to other sound classes that respond to speech therapy. Orthodontic
      and Maxillo facial surgery consultation might be needed when providing therapy to
      individuals with this particular articulation disorder.

PMID- 25861879
TI  - Temporal context and the organisational impairment of memory search in
      schizophrenia.
AB  - INTRODUCTION: An influential theory of schizophrenic deficits in executive
      function suggests that patients have difficulty maintaining and utilising an
      internal contextual representation, whose function is to ensure that stimuli are
      processed in a task-appropriate manner. In basic research on episodic memory,
      retrieved-context theories propose that an internal contextual representation is
      critically involved in memory search, facilitating the retrieval of task
      appropriate memories. This contextual machinery is thought to give rise to
      temporal organisation during free recall: the tendency for successive recall
      responses to correspond to items from nearby positions on the study list. If
      patients with schizophrenia have a generalised contextual deficit, then this
      leads to the prediction that these patients will exhibit reduced temporal
      organisation in free recall. METHODS: Using a combination of classic and recently
      developed organisational measures, we characterised recall organisation in 75
      patients with schizophrenia and 72 nondisordered control participants performing
      a multi-trial free-recall task. RESULTS: Patients with schizophrenia showed
      diminished temporal organisation, as well as diminished subjective organisation
      of their recall sequences relative to control participants. The two groups showed
      similar amounts of semantic organisation during recall. CONCLUSIONS: The
      observation of reduced temporal organisation in the patient group is consistent
      with the proposal that the memory deficit in schizophrenia can be characterised
      as a deficit in contextual processing.

PMID- 25861880
TI  - WITHDRAWN: Digital breast arterial calcium score is predictive of coronary
      calcium score.
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- 25861881
TI  - Erythropoietin attenuates intestinal inflammation and promotes tissue
      regeneration.
AB  - BACKGROUND: The prevalence of inflammatory bowel disease (IBD) is increasing.
      Since patients usually need long-term treatment and suffer from reduced quality
      of life, there is a need to develop new therapeutic strategy. The aim of this
      study was to investigate the therapeutic potential of erythropoietin (EPO) for
      the treatment of IBD. METHODS: Murine colitis was induced by 3.0% Dextran Sulfate
      Sodium (DSS). Recombinant human EPO (rhEPO) was given to evaluate the anti
      inflammatory and regenerative effects on intestinal inflammation. The effect of
      rhEPO on human colon epithelial cells was also evaluated. Immunohistochemical
      analysis of EPO receptor was performed in human IBD tissues. RESULTS: While about
      62% of control mice with severe colitis induced by 5-day DSS died, 85% of mice
      treated with rhEPO survived. Histological analysis confirmed that EPO treatment
      reduced the colonic inflammation. Furthermore, EPO treatment significantly
      downregulated the local expressions of IFN-gamma, TNF-alpha and E-selectin in the
      colon, suggesting that the effect was associated with inhibiting local immune
      activation. In a 4-day DSS-induced colitis model, rhEPO significantly improved
      the recovery of body weight loss compared to controls. Furthermore, proliferating
      cell nuclear antigen expression was significantly upregulated in the colon tissue
      from mice treated with rhEPO compared to controls. In addition, rhEPO increased
      the growth of cultured human colon epithelial cells in a dose-dependent manner.
      Furthermore, EPO-receptor expression was confirmed in human IBD colon tissues.
      CONCLUSION: Three major functions of EPO, hematopoiesis, anti-inflammation and
      regeneration, may produce significant effects on intestinal inflammation,
      therefore suggesting that rhEPO might be useful for IBD.

PMID- 25861882
TI  - Emerging PCSK9 inhibitors for treating dyslipidaemia: buttressing the gaps in
      coronary prevention.
AB  - INTRODUCTION: Atherosclerotic cardiovascular disease (ACVD) is the leading cause
      of mortality worldwide. An abnormally high plasma level of low-density
      lipoprotein-cholesterol is a major contributor to ACVD, an effect that can be
      attenuated by cholesterol-lowering therapies, particularly statins. A new class
      of drugs, the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors,
      will add another option for further reducing cardiovascular events in patients at
      high risk of ACVD, including those with familial hypercholesterolaemia (FH) and
      intolerance to statins. Patients with elevated levels of lipoprotein(a) (Lp(a))
      are difficult to treat with conventional therapies, and may also benefit from
      PCSK9 inhibitors. AREAS COVERED: This paper discusses the medical need for
      additional cholesterol-lowering therapies and the scientific rationale and
      current therapeutic status of PCSK9 inhibitors. EXPERT OPINION: The use of anti
      PCSK9 mAbs is the leading form of therapy for inhibiting PCSK9 and is likely to
      provide genuine hope for patients with FH, statin intolerance and elevated Lp(a).
      Their ability to reduce cardiovascular events in patients maximally treated with
      statins and other existing therapies remains to be proven, and is the subject of
      major ongoing clinical trials.

PMID- 25861883
TI  - Meta-analysis of the effects of peer-administered psychosocial interventions on
      symptoms of depression.
AB  - Many community mental health centers have implemented peer treatment models that
      employ recovered former clients as cost-efficient adjunct providers. The
      effectiveness of these and other peer-administered interventions (PAIs) for
      treating depression symptoms has not been well-established. The current study is
      a meta-analysis of PAIs' effects on depression symptoms. Twenty-three eligible
      studies were identified. Study characteristics were coded by multiple raters,
      random-effects models were used to compare mean effect sizes, and mixed-effects
      models were used to test for moderation. PAIs produced significant pre-post
      reductions in depression symptoms (d = .5043 [95 % CI .3675-.6412]). In direct
      comparisons, PAIs performed as well as non-peer-administered interventions (.0848
      [-.1455-.3151]), and significantly better than no-treatment conditions (.2011
      [.0104-.3918]). PAIs that involved a professional in a secondary treatment role
      were significantly less effective than those that were purely peer-administered,
      and educational/skills-based PAIs produced better outcomes than those that were
      mainly supportive. Follow-up data, when available, indicated that PAIs' benefits
      were maintained. PAIs reduce depression symptoms and warrant further study. The
      clinical significance of PAIs' benefits, and whether they are better suited as
      stand-alone or adjunct treatments, remain to be established. Implications for the
      roles of mental health professionals are discussed.

PMID- 25861884
TI  - Diagnostic utility of Acoustic Radiation Force Impulse (ARFI) imaging in primary
      Sjoegren's syndrome.
AB  - OBJECTIVES: The purpose of the study was to assess the diagnostic utility of
      acoustic radiation force impulse (ARFI) imaging in primary Sjogren's syndrome
      (pSS). METHODS: One hundred fifty-seven patients with sicca symptoms and/or
      salivary gland swelling were included. Sicca symptoms, Schirmer test,
      unstimulated whole saliva (UWS), SS-A/B antibodies, and histology were assessed
      according to American-European Consensus group (AECG) criteria. All patients
      underwent high-resolution ultrasound and ARFI imaging of the parotid (PG) and
      submandibular glands (SMG). RESULTS: Seventy patients were classified as having
      pSS. The remaining 87 patients suffered from idiopathic sicca (n = 24),
      rheumatoid arthritis (n = 12), sarcoidosis (n = 9), cutaneous/systemic lupus
      erythematosus (n = 7), scleroderma (n = 2), dermatomyositis (n = 1), HBV/HCV (n =
      2), and panarteritis nodosa (n = 1), and disorders in 29 patients were classified
      as not otherwise specified. ARFI values of the PG were significantly higher in
      the pSS versus non-pSS groups (2.86 +/- 0.07 m/s vs. 2.15 +/- 0.11 m/s, p <
      0.0001). ARFI imaging demonstrated diagnostic sensitivity and specificity of 81 %
      and 67 %, respectively. CONCLUSIONS: In addition to histology, ARFI imaging was
      the most important diagnostic tool for identifying early pSS. KEY POINTS: * Early
      stages in Sjogren's syndrome become apparent with major salivary gland
      enlargements. * Schirmer and unstimulated whole saliva tests demonstrated
      insufficient sensitivity/specificity for early-stage diagnosis. * Acoustic
      radiation force impulse imaging is a reliable tool for diagnosing early disease
      stages.

PMID- 25861885
TI  - Pathophysiologic changes in IA-2/IA-2beta null mice are secondary to alterations
      in the secretion of hormones and neurotransmitters.
AB  - IA-2 and IA-2beta are transmembrane proteins of dense-core vesicles (DCV). The
      deletion of these proteins results in a reduction in the number of DCV and the
      secretion of hormones and neurotransmitters. As a result, this leads to a variety
      of pathophysiologic changes. The purpose of this review is to describe these
      changes, which are characterized by glucose intolerance, female infertility,
      behavior and learning abnormalities and alterations in the diurnal circadian
      rhythms of blood pressure, heart rate, spontaneous physical activity and body
      temperature. These findings show that the deletion of IA-2 and IA-2beta results
      in multiple pathophysiologic changes and represents a unique in vivo model for
      studying the effect of hormone and neurotransmitter reduction on known and still
      unrecognized targets. 

PMID- 25861886
TI  - Radiation-induced malignant meningioma following proton beam therapy for a
      choroidal melanoma.
AB  - We report a woman with malignant meningioma diagnosed 9 years after the treatment
      of a choroidal melanoma with proton beam therapy. The risk of secondary cancers
      is a well-known adverse late effect of radiation therapy, especially with the use
      of advanced techniques such as intensity-modulated radiation therapy. However,
      this risk may be less with the use of proton beam therapy. A 79-year-old woman
      presented with symptoms of enophthalmos, ptosis and paralysis of the left medial
      rectus muscle. She had previously been successfully treated for a choroidal
      melanoma of the left eye with proton beam therapy (total dose: 60 cobalt gray
      equivalents) following local resection. MRI showed a lesion in the left cavernous
      sinus with extension into the orbit and a subsequent biopsy revealed a papillary
      meningioma. The cavernous tumor was treated with photon radiotherapy (total dose:
      54Gy) which achieved an initial partial response. However, 8 months later the
      tumor extensively metastasized to the skull and the spine and the patient died 1
      year after the treatment. The incidence of secondary malignancies after proton
      beam therapy is low but not negligible, therefore, it must be taken into account
      when planning a treatment as secondary tumors may present with a highly
      aggressive behaviour.

PMID- 25861887
TI  - Immunoglobulin-G4-related hypertrophic pachymeningitis with antineutrophil
      cytoplasmatic antibodies effectively treated with rituximab.
AB  - We describe a 52-year-old man with hypertrophic pachymeningitis (HP) who was both
      seropositive for antineutrophil cytoplasmatic antibodies (ANCA) against
      myeloperoxidase, and had an immunoglobulin G4 (IgG4) positive fibroinflammatory
      response in meningeal biopsy. HP is a chronic inflammatory thickening of the dura
      mater which typically presents with headache, cranial nerve dysfunction and other
      neurological deficits. While first-line treatment with corticosteroids is
      recommended, many patients relapse and need additional immunosuppression. One
      recently described etiology is IgG4-related disease and in a subgroup of
      idiopathic patients, evidence suggests a crucial role of ANCA. To our knowledge,
      the simultaneous occurrence of IgG4-related disease and ANCA has not been
      reported so far. This man suffered life-threatening disease progression despite
      the administration of high dose steroids, cyclophosphamide and azathioprine.
      Treatment with rituximab was initiated which led to disappearance of clinical
      symptoms and decrease of dural thickening within weeks. This patient presents a
      possible disease overlap of IgG4-related and ANCA-associated HP and illustrates
      the effectiveness of rituximab in refractory IgG4-related HP. 

PMID- 25861888
TI  - Optic nerve aspergillosis.
AB  - We report a 55-year-old woman with optic nerve Aspergillosis. Aspergillus is an
      ubiquitous airborne saprophytic fungus. Inhaled Aspergillus conidia are normally
      eliminated in the immunocompetent host by innate immune mechanisms; however, in
      immunosuppressed patients, they can cause disease. The woman had a past medical
      history of hypertension and migraines. She presented 1 year prior to death with a
      new onset headache behind the left eye and later developed blurred vision and
      scotoma. A left temporal artery biopsy was negative for giant cell arteritis. One
      month prior to the current admission, she had an MRI showing optic nerve
      thickening with no other findings. Because of the visual loss and a positive
      antinuclear antibody test, she was given a trial of high dose steroids and while
      it significantly improved her headache, her vision did not improve. At autopsy,
      the left optic nerve at the level of the cavernous sinus and extending into the
      optic chiasm was enlarged in diameter and there was a 1.3 cm firm nodule
      surrounding the left optic nerve. Histologically, an abscess surrounded and
      involved the left optic nerve. Acute angle branching, angioinvasive fungal hyphae
      were identified on Grocott's methenamine silver stained sections, consistent with
      Aspergillus spp. No gross or microscopic evidence of systemic vasculitis or
      infection was identified in the body. The literature on optic nerve Aspergillosis
      is reviewed.

PMID- 25861889
TI  - Postoperative segmental hypermobility after cervical arthroplasty: A possible
      pathomechanism for outcome failure.
AB  - We present a 41-year-old man who underwent a cervical discarthroplasty (CDA) C5-6
      procedure with an increase of the segmental range of motion from 2.8 degrees  to
      6.9 degrees  and an increase in disc height from 5.8mm preoperatively to 10.4mm
      postoperatively with an unfavorable long-term clinical outcome. Both anterior
      cervical discectomy with fusion (ACDF), as well as CDA have been proven to be
      successful procedures in the management of cervical radiculopathy with good to
      excellent outcomes and low complication rates. The rationale for CDA over ACDF
      highlights the preservation of segmental motion and reduction of the incidence of
      adjacent segment disease. This case report suggests that a hypermobility syndrome
      and also an overcorrection of the cervical range of motion may be responsible for
      an unfavorable outcome after CDA. 

PMID- 25861890
TI  - Post-operative Streptococcus pneumoniae meningoencephalitis complicating surgery
      for acromegaly in an identical twin.
AB  - This case report provides provocative and useful data regarding two aspects of
      acromegaly and its management. The patient, who is one of a pair of identical
      twins, has no known hereditary, genetic or otherwise potentially etiologic
      factors as compared to her unaffected sister. Secondly, transsphenoidal surgery,
      which was ultimately successful, was complicated by pneumococcal meningitis, an
      unusual event with only four previously reported patients, three of whom ended in
      death or major neurologic deficits. In this case, a 57-year-old woman gradually
      developed classical signs and symptoms of acromegaly while her identical twin
      sister remained normal with no evidence of endocrine disease. Endoscopic
      transsphenoidal surgery was complicated by the development of meningitis 25 days
      after surgery. This was controlled following a difficult hospital course.
      Streptococcus pneumoniae meningoencephalitis is a rare but life-threatening
      complication of transsphenoidal surgery. A high index of suspicion for incipient
      meningitis should be maintained when patients present with severe headache and
      increased intracranial pressure, even if they initially lack the typical symptoms
      and signs. Immediate and aggressive treatment is necessary to avoid significant
      neurologic deficit.

PMID- 25861891
TI  - Registration of 3D shapes under anisotropic scaling: Anisotropic-scaled iterative
      closest point algorithm.
AB  - PURPOSE: Several medical imaging modalities exhibit inherent scaling among the
      acquired data: The scale in an ultrasound image varies with the speed of sound
      and the scale of the range data used to reconstruct organ surfaces is subject to
      the scanner distance. In the context of surface-based registration, these scaling
      factors are often assumed to be isotropic, or as a known prior. Accounting for
      such anisotropies in scale can potentially dramatically improve registration and
      calibrations procedures that are essential for robust image-guided interventions.
      METHODS: We introduce an extension to the ordinary iterative closest point (ICP)
      algorithm, solving for the similarity transformation between point-sets
      comprising anisotropic scaling followed by rotation and translation. The proposed
      anisotropic-scaled ICP (ASICP) incorporate a novel use of Mahalanobis distance to
      establish correspondence and a new solution for the underlying registration
      problem. The derivation and convergence properties of ASICP are presented, and
      practical implementation details are discussed. Because the ASICP algorithm is
      independent of shape representation and feature extraction, it is generalizable
      for registrations involving scaling. RESULTS: Experimental results involving the
      ultrasound calibration, registration of partially overlapping range data, whole
      surfaces, as well as multi-modality surface data (intraoperative ultrasound to
      preoperative MR) show dramatic improvement in fiducial registration error.
      CONCLUSION: We present a generalization of the ICP algorithm, solving for a
      similarity transform between two point-sets by means of anisotropic scales,
      followed by rotation and translation. Our anisotropic-scaled ICP algorithm shares
      many traits with the ordinary ICP, including guaranteed convergence, independence
      of shape representation, and general applicability.

PMID- 25861892
TI  - The influence of osteophyte depiction in CT for patient-specific guided hip
      resurfacing procedures.
AB  - PURPOSE: An accurate fit of a patient-specific instrument guide during an
      intervention is one of the critical factors affecting accuracy of the surgical
      procedure. In this study, we investigated how well osteophytes, which are
      abnormal bone growths that form along joints, are depicted in clinical
      preoperative CT scans and estimated the influence of such depiction errors on the
      intraoperative accuracy of the guide. METHODS: In 34 hip resurfacing patients,
      227 osteophyte surface points on the anterior aspect of the femoral neck were
      collected intraoperatively, using an optoelectronic navigation system. These
      points were registered to a preoperative CT scan of the patient, and distances
      between collected points and segmented virtual bone surface, as well as
      Hounsfield units for these points, were determined. We simulated the registration
      error of a patient-specific guide, using a modified registration algorithm, to
      test placement on the anterior aspect of the femoral neck without removing any
      osteophytes. This error was then applied to the surgical plan of the femoral
      central-pin position and orientation for evaluation. RESULTS: The average
      distance between the collected points and the segmented surface was 2.6 mm. We
      estimated the average error for the entrance point of the central-pin to be 0.7
      mm in the distal direction and 3.2 mm in the anterior direction. The average
      orientation error was 2.8 degrees  in anteversion. CONCLUSIONS: The depiction of
      osteophytes in clinical preoperative CT scans for proximal femurs can be
      unreliable and can possibly result in significant intraoperative instrument
      alignment errors during image-guided surgeries.

PMID- 25861893
TI  - Message from the Editors-in-Chief.

PMID- 25861894
TI  - Perioperative high-dose-rate interstitial brachytherapy combined with external
      beam radiation therapy for soft tissue sarcoma.
AB  - PURPOSE: The aim of our study was to evaluate the role of perioperative high-dose
      rate interstitial brachytherapy (PHDRIBT) in combination with external beam
      radiation therapy (EBRT) in patients with localized soft tissue sarcoma (STS).
      METHODS AND MATERIALS: From year 2004 to 2010, 52 patients with localized STS
      were treated with wide local excision plus PHDRIBT followed by EBRT. Median size
      of the tumor was 8 cm (range, 4-19 cm). A single-plane interstitial brachytherapy
      implant with an average of nine catheters was performed during the surgical
      resection. The PHDRIBT was started on third postoperative day to deliver a high
      dose-rate dose of 16 Gy in four fractions over 2 days using twice-a-day
      fractionation schedule. After 4 weeks, EBRT was started for a prescription dose
      of 50 Gy by conventional fractionation. Subsequently, chemotherapy was
      administered, if indicated as per our institutional policy. Patients were
      followed up regularly to study local control, survival, and toxicity. RESULTS: At
      a median followup of 46 months, no patient developed local recurrence, but 12
      patients developed distant metastases. The 5-year overall survival and disease
      free survival were 67% and 63%, respectively. Main acute toxicity was delayed
      wound healing observed in 3 patients (5.7%). Commonest late toxicity was chronic
      skin/subcutaneous fibrosis noticed in 5 patients (9.6%). CONCLUSIONS: The PHDRIBT
      combined with EBRT provides excellent local control and survival rates with
      acceptable acute and late toxicity in patients with localized STS.

PMID- 25861895
TI  - [Arachnoid cysts of the central nervous system. Algorithms and recommendations
      for management].
AB  - The symptoms related to the presence of arachnoid cysts in the Central Nervous
      System depend on the size of the cyst and its growth rate, its location and, in
      some cases, the associated CSF dynamic disorder. Sometimes there is acute
      clinical presentation due to cyst rupture or acute bleeding. Although it is
      generally accepted that asymptomatic or paucisymptomatic cysts do not require
      surgical treatment, there is no consensus on the therapeutic approach of choice
      in symptomatic cases. The aim of this paper is to review the literature,
      analyzing the pros and cons of the three main surgical options (microsurgery,
      neuroendoscopy, and CSF shunt) based primarily on the location of the cyst.
      Although treatment must be always individualized, basic management
      recommendations may be offered. 

PMID- 25861896
TI  - Aesthetically optimal deep brain stimulation technique in patients with alopecia.

PMID- 25861897
TI  - [Vestibular schwannomas: Surgical treatment of 67 cases in 10 years].
AB  - INTRODUCTION: Vestibular Schwannomas (VS) are benign intracranial tumors, for
      which their current management is a matter of debate, although microsurgical
      treatment remains the mode of choice in the majority of cases. OBJECTIVE: To
      describe the surgical outcome of patients operated on for a VS in a Chilean
      Public Hospital. MATERIAL AND METHOD: A series of 67 patients treated surgically
      between 2002 and 2012, in the Institute of Neurosurgery Asenjo is presented.
      RESULTS: Sixty-five cases (97%) corresponded to Koos III and IV tumors, of which
      52% were large (3-4 cm) or Giant (>4 cm). Forty-one cases were operated on using
      a retrosigmoid transmeatalapproach (61%). Total resection was achieved in 97% of
      the cases and subtotal in the remaining 3%. A mean six months follow-up showed
      that good facial function (House-Brackmann I or II) was obtained in 32.7% of the
      patients, and moderate function (House-Brackmann III or IV) in 42.3%.
      Cardiopulmonary complications were the most frequent (28%), and mortality was
      1.5%. CONCLUSIONS: The VS are tumors that can cause significant neurological
      deficit in advanced stages, despite their benign nature. Surgical treatment is
      very complex, and must be performed by specialized teams to ensure optimal
      functional results.

PMID- 25861898
TI  - Do participants in adjuvant breast cancer trials reflect the breast cancer
      patient population?
AB  - AIM: To describe the proportion of women in Tayside, Scotland diagnosed with
      early breast cancer who would have been eligible for influential adjuvant breast
      cancer trials. METHODS: Phase III trials of adjuvant treatment for breast cancer
      referenced in five national guidelines were shortlisted by breast cancer
      specialists to identify the twelve considered most influential. Eligibility
      criteria were extracted from protocols and applied to a 16-year cohort of women
      who had received a diagnosis of breast cancer and the proportion meeting trial
      criteria calculated. The criteria used clinically in Tayside to make decisions
      about use of the trial treatments were also applied to the cohort. Finally, the
      proportion of women receiving adjuvant endocrine therapy as part of their care
      and who would have been eligible for the trial evaluating that therapy was
      calculated. RESULTS: Of the cohort's 4811 women, 3535 (73%) were eligible for at
      least one trial but eligibility for an individual trial rarely exceeded 45%.
      There were substantial differences between the proportion of women meeting trial
      eligibility criteria and the proportion considered clinically eligible for the
      same treatment. The proportion of women receiving an endocrine therapy as part of
      their care who would also have been eligible for the trial evaluating that
      treatment ranged from 17% to 56%. CONCLUSION: Clinical eligibility criteria may
      be at variance with trial criteria. For adjuvant endocrine therapy, a substantial
      proportion of women who would have been ineligible for a trial nevertheless
      received the trial treatment as part of their care.

PMID- 25861899
TI  - Exploring the structural constraints at cleavage site of mucin 1 isoform through
      molecular dynamics simulation.
AB  - In silico alanine scanning mutagenesis on the cleavable isoform of mucin 1
      revealed isoleucine 67 as one of the key factors contributing to the strain at
      the autoproteolytic cleavage site. In this study, we demonstrate the structural
      basis of isoleucine-induced rigidity towards the strain-driven autoproteolysis at
      G(-1)S(+1) cleavage site of mucin 1. We further evaluated the gain in flexibility
      upon isoleucine 67 mutation through molecular dynamics and essential dynamics
      studies. The results show that the mutant exhibits stability in its secondary
      structural elements while the native displays a less-bonded network, however the
      cleavage site of native remains constrained. Essential dynamics revealed that
      large motions of the mutant were confined to the loop although the internal
      domain of the structure remains unaffected. Also, the mutation exerted a larger
      effect on the intraprotein interactions and consequently resulted in a stabilized
      motif at the cleavage. Analyses on MD trajectory conformations illustrate a
      completely disrupted motif in native as an effect of the peptide strain. The
      study also revealed that in mutant, the cleavage competent catalytic groups C=O
      and OG were in geometrical aspects unfavorable for a nucleophilic attack. The
      results support the earlier speculation that the presence of bulky isoleucine
      proximal G(-1)S(+1) cleavage site limits the conformational sampling of residues
      and therefore maintains the residues in a torsionally restrained conformation. 

PMID- 25861900
TI  - Perfluoroalkyl acids in selected wastewater treatment plants and their discharge
      load within the Lake Victoria basin in Kenya.
AB  - A major ecological challenge facing Lake Victoria basin is the influx of chemical
      contaminants from domestic, hospital, and industrial effluents. Determined levels
      of perfluoroalkyl acids (PFAAs) in wastewater and sludge from selected wastewater
      treatment plants (WWTPs) in Kenya are presented and their daily discharge loads
      calculated for the first time within the Lake Victoria basin. Samples were
      extracted and separated using solid-phase extraction and ultra-performance liquid
      chromatography (UPLC)-MS/MS or LC-MS/MS methodology. All sewage sludge and
      wastewater samples obtained from the WWTPs contained detectable levels of PFAAs
      in picogram per gram dry weight (d.w.) and in nanogram per liter, respectively.
      There was variability in distribution of PFAAs in domestic, hospital, and
      industrial waste with domestic WWPTs observed to contain higher levels. Almost
      all PFAA homologues of chain length C-6 and above were detected in samples
      analyzed, with long-chain PFAAs (C-8 and above chain length) being dominant. The
      discharge from hospital contributes significantly to the amounts of PFAAs
      released to the municipal water systems and the lake catchment. Using the average
      output of wastewater from the five WWTPs, a mass load of 1013 mg day(-1) PFAAs
      per day discharged has been calculated, with the highest discharge obtained at
      Kisumu City (656 mg day(-1)). The concentration range of perfluorooctanoic acid
      (PFOA) and perfluorooctane sulfonate (PFOS) in wastewater was 1.3-28 and 0.9-9.8
      ng L(-1) and in sludge samples were 117-673 and 98-683 pg g(-1), respectively. 

PMID- 25861901
TI  - The size distribution and origin of elements bound to ambient particles: a case
      study of a Polish urban area.
AB  - Ambient particulate matter (PM) was sampled in Zabrze (southern Poland) in the
      heating period of 2009. It was investigated for distribution of its mass and of
      the masses of its 18 component elements (S, Cl, K, Ca, Cr, Mn, Fe, Ni, Cu, Zn,
      Ge, As, Br, Sr, Cd, Sb, Ba, and Pb) among 13 PM size fractions. In the paper, the
      distribution modality of and the correlations between the ambient concentrations
      of these elements are discussed and interpreted in terms of the source
      apportionment of PM emissions. By weight, S, Cl, K, Ca, Cr, Mn, Fe, Ni, Cu, Zn,
      Ge, As, Br, Sr, Cd, Sb, Ba, and Pb were 10% of coarse and 9% of ultrafine
      particles. The collective mass of these elements was no more than 3.5 % of the
      mass of the particles with the aerodynamic diameter D p between 0.4 and 1.0 MUm
      (PM0.4-1), whose ambient mass concentration was the highest. The PM mass size
      distribution for the sampling period is bimodal; it has the accumulation and
      coarse modes. The coarse particles were probably of the mineral/soil origin
      (characteristic elements: Ca, Fe, Sr, and Ba), being re-suspended polluted soil
      or road dust (characteristic elements: Ca, Fe, Sr, Ba, S, K, Cr, Cu, Zn, Br, Sb,
      Pb). The maxima of the density functions (modes) of the concentration
      distributions with respect to particle size of PM-bound S, Cl, K, Cu, Zn, Ge, Br,
      Cd, Sb, and Pb within the D p interval from 0.108 to 1.6 MUm (accumulation PM
      particles) indicate the emissions from furnaces and road traffic. The
      distributions of PM-bound As, Mn, Ba, and Sr concentrations have their modes
      within D p <= 0.108 MUm (nucleation PM particles), indicating the emissions from
      high-temperature processes (industrial sources or car engines). In this work,
      principal component analysis (PCA) is applied separately to each of the 13
      fraction-related sets of the concentrations of the 18 PM-bound elements, and
      further, the fractions are grouped by their origin using cluster analysis (CA)
      applied to the 13 fraction-related first principal components (PC1). Four
      distinct groups of the PM fractions are identified: (PM1.6-2.5, PM2.5-4.4,),
      (PM0.03-0.06, PM0.108-0.17), (PM0.06-0.108, PM0.17-0.26, PM0.26-0.4, PM0.4-0.65,
      PM0.65-1, PM1-1.6), and (PM4.4-6.8, PM6.8-10, PM>10). The PM sources attributed
      to these groups by using PCA followed by CA are roughly the same as the sources
      from the apportionment done by analyzing the modality of the mass size
      distributions.

PMID- 25861902
TI  - Driving forces of heavy metal changes in agricultural soils in a typical
      manufacturing center.
AB  - Heavy metal concentrations in 2002 and 2012 in agricultural soils in Dongguan, a
      manufacturing center in southern China, were analyzed to determine the impact of
      rapid economic development on soil pollution. The level of pollution was assessed
      using the Nemerow synthetic pollution index (NPI), and its changing
      characteristics and driving forces were analyzed using multivariate statistical
      and geostatistical methods. The results indicate that the mean NPI was 0.79 in
      2002 and 0.84 in 2012, which indicates aggravated heavy metal contamination in
      the agricultural soils. The concentrations of Cd and Zn increased 54.7 and 20.8
      %, respectively, whereas Hg and Pb decreased 35.3 and 24.5 %, respectively. Cr,
      As, Cu, and Ni remained relatively stable. The Hg and Cd concentrations were
      highly correlated with soil types (P < 0.01), the secondary industrial output per
      unit of land (P < 0.01), proportion of cereal fields (P < 0.01), proportion of
      vegetable fields (P < 0.01), population density (P < 0.05), and road density (P <
      0.05). The Pb and As concentrations were greatly influenced by soil types (P <
      0.01), river density (P < 0.01), fertilizer rate (P < 0.01), and road density (P
      < 0.05). Cr, Zn, Cu, and Ni concentrations were primarily driven by soil types (P
      < 0.01), river density (P < 0.01), and fertilizer rate (P < 0.05). 

PMID- 25861903
TI  - Effect of mercury on seedling growth, nodulation and ultrastructural deformation
      of Vigna radiata (L) Wilczek.
AB  - Heavy metals are major environmental pollutant when they present in high
      concentration in soil and have toxic effects on growth, nodulation and nitrogen
      fixation of legumes and development of plants. Mercury stress triggers
      disturbances in cellular structure, and metabolismn is poorly understood. The
      response of seedling growth and nodulation of Vigna radiata (L) Wilczek to
      different concentrations (0.1, 0.5, 1.0 and 1.5 ppm) of mercury (Hg) salt
      solutions were studied. Morphological parameters like root and shoot length, dry
      weight, nodule number, total leaf area and biochemical constituents (chlorophyll,
      malondialdehyde and leghaemoglobin) of bean plants were recorded at an interval
      of 30 days. The successive growth deformaties in seedlings and nodules were
      recorded at lower concentration (0.1 ppm), but marginal (0.5 ppm) and higher (1.0
      ppm) level of Hg salt solution showed significant suppression. The maximum level
      of Hg concentration (1.5 ppm) shows high level of tolerance index without any
      nodule. The control treatment shows maximum level of leghaemoglobin (0.219 mM)
      and all other morpho-physiological and bio-chemical properties of roots and
      shoots excepting tolerance index (0.00) and chlorophyll 'a' (7.52 mg g(-1) FW).
      Mercury accumulation pattern follows the sequences: leaf > nodule > root ~ shoot
      at lower level of Hg (0.1 and 0.5 ppm). However, higher level of Hg (1.0 and 1.5
      ppm) showed shoot > root > leaf > nodule. The scanning electron microscopy (SEM)
      study of root also highlights the deleterious effect of Hg salt at higher
      concentration. 

PMID- 25861904
TI  - Comparison of laparoscopic versus open left-sided hepatectomy for intrahepatic
      duct stones.
AB  - BACKGROUND: Laparoscopic hepatectomy for intrahepatic duct (IHD) stones is
      limited by technical difficulties caused by adhesion to adjacent tissue or
      distorted anatomy resulting from recurrent inflammation. This study compared
      perioperative and clinical outcomes in patients undergoing laparoscopic and open
      hepatectomy for left IHD stones. METHODS: From January 2002 to December 2013, 40
      patients underwent laparoscopic left-sided hepatectomy [left hemihepatectomy (n =
      7) or left lateral sectionectomy (n = 33)] and 54 patients without combined
      operations and previous operation histories underwent open left-sided hepatectomy
      [left hemihepatectomy (n = 24) or left lateral sectionectomy (n = 30)]. Their
      perioperative and clinical outcomes were compared, including stone clearance
      rates, stone recurrence rates, and median follow-up duration. RESULTS: There was
      no difference in age (56.8 +/- 8.2 vs. 55.6 +/- 9.6 years, p = 0.531), sex
      (1.0:4.0 vs. 1.0:1.8 male:female, p = 0.108), or BMI (22.8 +/- 2.8 vs. 22.9 +/-
      3.0 kg/m(2), p = 0.802) between the laparoscopic and open hepatectomy groups.
      Lateral sectionectomy was more frequent in the laparoscopic group (33/40 vs.
      30/54, p = 0.010). Operation time (174.2 +/- 56.6 vs. 210.4 +/- 51.6 min, p =
      0.002) and postoperative hospital stay (7.9 +/- 2.6 vs. 14.3 +/- 5.5 days, p <
      0.001) were shorter in the laparoscopic group, and complication rate (17.5 vs.
      40.7%, p = 0.016), in particular surgical site infection rate (5.0 vs. 18.5%, p =
      0.052), was lower in the laparoscopic group than in the open hepatectomy group.
      Similar results were observed in the hemihepatectomy and lateral sectionectomy
      subgroups. There was no operation-related mortality. There were no significant
      differences in follow-up periods (48 +/- 33.6 vs. 59.2 +/- 41.7 months, p =
      0.235) and rates of initial stone clearance (87.5 vs. 75.9%, p = 0.159), final
      clearance (100 vs. 94.4%, p = 0.130), and stone recurrence (2.5 vs. 5.6%, p =
      0.468). CONCLUSION: Laparoscopic hepatectomy is safe and effective for well
      selected patients with left IHD stones, when performed by experienced surgeons.
      Laparoscopic hepatectomy resulted in shorter operation time and postoperative
      hospital stay, and a lower postoperative morbidity rate, than open hepatectomy.

PMID- 25861905
TI  - Robotic single-site versus laparoscopic cholecystectomy: Which is cheaper? A cost
      report and analysis.
AB  - OBJECTIVE: There is a need for a comparison of costs of robotic single-site
      cholecystectomy (RSSC) and laparoscopic cholecystectomy (LC) in the US healthcare
      model. Cholecystectomy is one of the most common procedures in general surgery.
      Single-incision laparoscopic surgery is beneficial but cumbersome. Robotic
      surgery is ergonomic but expensive. Costs of RSSC and LC have not been compared
      within the US healthcare model. METHODS: Cost categories were compared between
      RSSC and LC in consecutive outpatient-elective cases during the same period. Cost
      efficiency of outpatient-elective cases before and after the first 50
      institutional RSSC cases (including outpatients, inpatients, emergent, and
      elective) were compared to investigate for a learning curve that would
      subsequently affect cost. RESULTS: A total of 458 cases included 177 RSSCs and
      281 LCs. Non-emergent non-admitted cases included in cost analysis were 46 RSSCs
      and 175 LCs. Costs were less with RSSC: median total ($1319 vs. $1710, p <
      0.001), driven mainly by cost category "Supplies" ($913 vs. $1244, p < 0.001),
      and to a lesser extent "Operating room" ($196 vs. $232, p < 0.001), and
      "Anesthesiology" ($127 vs. $168, p < 0.001). Supplies were responsible for 87% of
      median total cost reduction. Other cost categories were not significantly
      different. There were 11 and 9% drops (p < 0.006) in RSSC OR times and costs,
      respectively, after our 50th institutional case. CONCLUSION: In a hospital that
      has already acquired infrastructure for robotic surgery, we observed procedural
      costs for RSSC that were lower than LC. This decreased cost was mainly driven by
      cutting down on supplies (87% of median total cost reduced), and to a lesser
      extent OR time. A steep learning curve exists after which RSSC OR times can be
      significantly shortened. A randomized study is needed.

PMID- 25861906
TI  - Assessment of perioperative complications following primary bariatric surgery
      according to the Clavien-Dindo classification: comparison of sleeve gastrectomy
      and Roux-Y gastric bypass.
AB  - BACKGROUND: Laparoscopic Roux-Y gastric bypass (LRYGBP) is the gold-standard
      procedure for the treatment of morbid obesity. It has been reported to be
      somewhat more efficient and durable than laparoscopic sleeve gastrectomy (LSG).
      However, it is considered more invasive and, therefore, more hazardous. There is
      a lack of unity in complication reporting following bariatric surgery. Thus,
      there is a possible misconception regarding the relative safety of the two major
      bariatric procedures performed worldwide. This may have contributed to a shift in
      practice with LSG gaining momentum "at the expense" of LRYGBP. The aim of this
      study was to evaluate the relative safety of primary LSG and LRYGBP according to
      the Clavien-Dindo complication grading system. METHODS: A total of 2651 and 554
      patients underwent primary LSG and LRYGBP, respectively at three high-volume
      centers. Thirty-day perioperative complications were recorded and graded. Length
      of hospital stays (LOS) and readmission rates were collected as well. RESULTS:
      Complications occurred in 110 (3.7%) and 24 (4.3%) patients following LSG and
      LRYGBP, respectively (p = 0.9). No significant difference was found between the
      groups regarding overall and complication-grade-specific rates. Individual
      complication types were unevenly distributed, but not significantly so. Patients
      with complications were older than those without (47 and 43 years, respectively;
      p = 0.01). Gender was not a risk factor for complication. Median LOS and
      readmission rates were not significantly different. CONCLUSIONS: LSG and LRYGBP
      are equally safe, at least in the perioperative period. Acknowledging and
      conveying this finding to surgeons and patients alike is important and might
      cause a pendulum shift in the distribution of bariatric procedures performed.

PMID- 25861907
TI  - Endocuff-assisted colonoscopy increases polyp detection rate: a simulated
      randomized study involving an anatomic colorectal model and 32 international
      endoscopists.
AB  - BACKGROUND: The undetected colonic lesions behind the folds and flexures are a
      major factor contributing to the adenoma miss rate. OBJECTIVE: To assess the
      efficacy of Endocuff, a special attachment was fixed at the distal tip of a
      colonoscope, for the polyp detection. This soft accessory is composed of a
      plastic cap surrounded by flexible finger-like projections on the lateral sides
      of the cap that make holding of the folds during scope withdrawal easier. DESIGN:
      This was a simulated pilot study with one anatomic colorectal model, containing
      13 polyps positioned in obvious locations and behind the folds. Thirty-two
      endoscopists (16 Japanese and 16 foreign visitors) with different levels of
      experience performed examinations on the model in a randomized order by using
      Endocuff-assisted colonoscopy (EAC) and standard colonoscope (SC). MAIN OUTCOME
      MEASUREMENTS: To assess the detection rate of polyps and the feasibility of
      Endocuff insertion. RESULTS: EAC detected significantly more polyps than SC with
      9.9 versus 7.5 mean lesions (p = 0.03), respectively, comparing the 16 first
      colonoscopies in each group. Endocuff was useful independent of the level of
      experience of the participants. After crossover, EAC in second position allowed
      an additional detection of 1.8 polyps compared with SC (p = 0.001). After
      adjustment on experience, time of detection, and order of colonoscopy, EAC over
      detected 1.2 polyps (p = 0.0037). The insertion time (p = 0.99) was identical.
      There was no difference in the mean time of polyp detection between EAC and SC
      groups (p = 0.520). LIMITATIONS: This was not a clinical study. The stiffness of
      the folds in the colonic model was higher than in the human large bowel.
      CONCLUSION: EAC was associated with a higher polyp detection rate. Even in such
      relatively stiff anatomic model, it was easier to spread out the colonic mucosa
      between the folds using this cap. This study provides an additional argument for
      the routine application of this easy-to-use accessory to improve polyp detection.

PMID- 25861908
TI  - Tenofovir-Associated Nephrotoxicity in Children with Perinatally-Acquired HIV
      Infection: A Single-Centre Cohort Study.
AB  - BACKGROUND AND OBJECTIVE: In 2012, tenofovir disoproxil fumarate (TDF) was
      approved for use in children over 2 years of age at a dose of 8 mg/kg/day, and is
      the WHO recommended first-line therapy for children over 10 years of age or 35 kg
      in weight, at 300 mg daily. Whilst postmarketing experience of paediatric TDF is
      limited, prior off-licence use has occurred at our centre due to its
      tolerability, efficacy and resistance profiles. In this article we describe a
      single-centre experience of TDF nephrotoxicity in children aged <16 years.
      METHODS: We conducted a retrospective case-note audit of children with
      perinatally-acquired HIV who ever received TDF-based antiretroviral therapy.
      RESULTS: From 2001 to December 2013, 70 children [39 (56 %) females] ever
      received TDF. Median age at the start of TDF treatment was 12 years
      (interquartile range 10-14). Seven (10 %) children developed asymptomatic renal
      tubular leak with associated hypophosphataemia (3) and hypokalaemia (1), all
      resulting in TDF withdrawal and biochemical resolution. Comparison of the
      nephrotoxic group versus the rest of the cohort showed no significant differences
      for age, sex, antiretroviral regimen or CD4 count. Lower weight (p = 0.05) and
      initial dose of TDF received (p = 0.0048) were significantly associated with TDF
      induced nephrotoxicity: median dose of TDF (7.8 mg/kg/day) compared with the
      remainder of the cohort (6.5 mg/kg/day). Concurrent use of protease inhibitors
      (PIs) with TDF may be a contributing factor to the development of nephrotoxicity
      (odds ratio 6; 95 % CI 0.7-54; p = 0.111). CONCLUSION: Although all children with
      TDF-associated nephrotoxicity had biochemical resolution on drug withdrawal,
      renal monitoring of children receiving TDF is important, especially with the co
      administration of PIs. Postmarketing surveillance is essential in the paediatric
      setting.

PMID- 25861909
TI  - Future directions for positive body image research.
AB  - The emergence of positive body image research during the last 10 years represents
      an important shift in the body image literature. The existing evidence provides a
      strong empirical basis for the study of positive body image and research has
      begun to address issues of age, gender, ethnicity, culture, development, and
      intervention in relation to positive body image. This article briefly reviews the
      existing evidence before outlining directions for future research. Specifically,
      six areas for future positive body image research are outlined: (a)
      conceptualization, (b) models, (c) developmental factors, (d) social
      interactions, (e) cognitive processing style, and (f) interventions. Finally, the
      potential role of positive body image as a protective factor within the broader
      body image literature is discussed. 

PMID- 25861910
TI  - Assessment of ecological quality of the Tajan River in Iran using a multimetric
      macroinvertebrate index and species traits.
AB  - The objectives of this study were to assess the biological water of the Iranian
      Tajan River using different metrics, i.e., a Multimetric Macroinvertebrate Index
      (MMI) and a traits-based method. Twenty-eight physico-chemical parameters, 10
      habitat factors, and abundance of macroinvertebrates were obtained for 17 sites.
      The Shahid-Rajaie dam divides the Tajan River into an up- and downstream part,
      with different land uses. Eighteen metrics were used to represent four components
      of ecosystem quality, including tolerance (Hilsenhoff, SIGNAL), diversity
      (Margalef, Shannon-Wiener, Simpson, and Evenness), abundance (total number of
      taxa, individuals, Ephemeroptera, Plecoptera, Trichoptera, EPT, and Insects), and
      composition of assemblages (% Ephemeroptera, % Plecoptera, % Trichoptera, and %
      EPT Taxa). The integrated MMI was calculated by averaging the obtained scores of
      all indices. In the next step, we gathered information on 22 biological traits of
      macroinvertebrates to evaluate whether (group of) traits could be identified that
      are indicative for specific or general stress. Result showed a decrease in MMI
      from upstream (very good water quality) to downstream (bad) due to human
      activities. Industrial activities like pulping and papermaking operations or sand
      mining in the downstream part had more effects than agriculture and fish ponds in
      the upstream part. A redundancy analysis biplot showed the variation between the
      modalities of trait of macroinvertebrates and their correlation with physico
      chemical parameters in Tajan River. The findings show that traits can be
      indicative for different kind of stress but that more effort has to be put in
      gathering data sets to disentangle the effect of habitat quality, pollution, and
      the physico-chemical properties of high- versus lowland rivers. 

PMID- 25861911
TI  - Comparison of intraoperative time measurements between osseous reconstructions
      with free fibula flaps applying computer-aided designed/computer-aided
      manufactured and conventional techniques.
AB  - PURPOSE: We aimed to determine whether computer-aided designed/computer-aided
      manufactured (CAD/CAM) techniques could save intraoperative time compared with
      the conventional technique, by comparing flap harvesting and ischemia times, and
      subsequently impact flap survival. METHODS: Twenty patients underwent concurrent
      osteocutaneous fibula flaps, either with (n = 10) or without (n = 10) the CAD/CAM
      technique. Demographic data, clinical history, complications, number of osseous
      segments, and times for virtual planning, flap harvesting, flap ischemia,
      tourniquet inflation, and total reconstruction were recorded. RESULTS: There was
      no significant difference between CAD/CAM and conventional techniques with
      respect to age, number of osseous segments, complication rates, and tourniquet
      inflation time. Flap harvesting times were significantly shorter in the
      conventional group (112.1 vs. 142.2 min, p < 0.001), while flap ischemia and
      total ischemia times were significantly shorter in the CAD/CAM group (70.7 vs.
      98.6 min, p < 0.001; 174.8 vs. 198.9 min, p = 0.002, respectively). However,
      while total reconstruction time did not differ between groups, overall operating
      time (including the amount of virtual planning time and surgical reconstruction
      time) was significantly longer in the CAD/CAM group (mean 256.0 vs. 210.7 min, p
      < 0.001). CONCLUSIONS: Despite the advantages of the CAD/CAM technique, including
      reduced ischemia time of osteocutaneous fibula flaps, there is no impact on total
      reconstruction time or flap survival.

PMID- 25861912
TI  - Psychometric properties of the Chinese (Cantonese) versions of the KIDSCREEN
      health-related quality of life questionnaire.
AB  - PURPOSE: The KIDSCREEN questionnaire assesses health-related quality of life in
      children and adolescents. In this study, the questionnaire was translated into
      Chinese (Cantonese) and administered to two independent groups of Hong Kong
      Chinese students. Various aspects of reliability and validity of the KIDSCREEN-52
      and KIDSCREEN-27 questionnaires were examined. METHODS: The translated KIDSCREEN
      52 questionnaire (and thus the KIDSCREEN-27 as a subset of the long form) was
      administered to cohorts of 1379 and 555 students. Confirmatory factor analysis
      and partial credit Rasch analyses were used to examine the underlying structure
      of the instrument. Test-retest reliability, convergent, and divergent validity
      were also examined. RESULTS: The 10-factor structure of the Chinese KIDSCREEN-52
      was supported. However, the original five-factor model of the KIDSCREEN-27 was
      not supported as seven distinct factors were found. Internal consistency and test
      retest reliability were acceptable. Evidence supporting convergent and divergent
      validity was found. CONCLUSIONS: Results from the two studies supported the use
      of the translated Chinese version of KIDSCREEN questionnaire children and
      adolescents' health-related quality of life. Further research is required to
      examine possible cultural or language differences between the original version
      and the translated Chinese version of the questionnaire.

PMID- 25861913
TI  - A Facile Vortex-Assisted Dispersive Liquid-Liquid Microextraction Method for the
      Determination of Uranyl Ion at Low Levels by Spectrophotometry.
AB  - A facile and reliable UV-Vis spectrophotometric method associated with vortex
      assisted dispersive liquid-liquid microextraction has been developed and applied
      to the determination of U(VI) at low levels in water samples. It was based on
      preconcentration of 24.0 mL sample at pH 8.0 in the presence of 7.4 umol L(-1) 1
      (2-pyridylazo)-2-naphthol, 1.0 mL of methanol as disperser solvent and 1.0 mL of
      chloroform as extraction solvent. A high preconcentration factor was achieved
      (396 times), thus providing a wide analytical curve from 6.9 up to 75.9 ug L(-1)
      (r=0.9982) and limits of detection and quantification of 0.40 and 1.30 ug L(-1),
      respectively. When necessary, EDTA or KCN can be used to remove interferences of
      foreign ions. The method was applied to the analysis of real water samples, such
      as tap, mineral and lake waters with good recovery values.

PMID- 25861914
TI  - A new naphthalene glycoside from Chimaphila umbellata inhibits the RANKL
      stimulated osteoclast differentiation.
AB  - A new naphthalene glycoside was isolated from the leaves and stems of Chimaphila
      umbellata Barton. Its chemical structure was elucidated to be 2,7-dimethyl-1,4
      dihydroxynaphthalene-1-O-beta-D-glucopyranoside (DMDHNG), based on spectroscopic
      evidence. DMDHNG significantly inhibited the receptor activator of nuclear factor
      kappaB ligand (RANKL)-induced tartrate-resistant acid phosphatase (TRAP) activity
      and the formation of multinucleated osteoclasts in a dose-dependent manner. In
      addition, the new glycoside inhibited the RANKL-induced mRNA expression of
      osteoclast-associated genes that encode TRAP, cathepsin K, and another
      transcription factor-nuclear factor of activated T-cells c1. We believe that the
      inhibitory effects of DMDHNG on the osteoclast differentiation may be exploited
      for a therapeutic benefit. 

PMID- 25861915
TI  - Effect of N-terminal truncation on antibacterial activity, cytotoxicity and
      membrane perturbation activity of Cc-CATH3.
AB  - A series of amino-terminal truncated analogues of quail antimicrobial peptide Cc
      CATH3(1-29) were created and examined antibacterial activity against Gram
      positive bacteria, cytotoxicity against mouse fibroblast cell line, and membrane
      perturbation activity against various membrane models. Parent peptide Cc-CATH3(1
      29) and the first four-residue truncated peptide Cc-CATH3(5-29) were active in
      all tested experiments. In contrast, the eight- and twelve-residue truncated
      variants Cc-CATH3(9-29) and Cc-CATH3(13-29) appeared to have lost activities. Cc
      CATH3(1-29) and Cc-CATH3(5-29) possessed antibacterial activity with minimum
      inhibitory concentrations of 2-4 and 1-2 uM, respectively. For cytotoxicity, Cc
      CATH3(1-29) and Cc-CATH3(5-29) displayed cytotoxicity with the IC50 values of
      9.33 and 4.93 MUM, respectively. Cc-CATH3(5-29) induced greater liposome
      membranes disruption than Cc-CATH3(1-29) regardless of lipid type and
      composition. The leakage results of Cc-CATH3(1-29) share a similar trend with
      that in Cc-CATH3(5-29); they exhibit no preferential binding to anionic
      phospholipids. In conclusion, the results suggested that the first four residues
      at the N-terminus "RVRR" is not essential for presenting all test activities. In
      contrast, residues five to eight of "FWPL" are necessary as the exclusion of this
      short motif in Cc-CATH3(9-29) and Cc-CATH3(13-29) leads to a loss of activities.
      This study will be beneficial for further design and development of Cc-CATH3 to
      be novel antibiotic.

PMID- 25861917
TI  - A time and space complexity reduction for coevolutionary analysis of trees
      generated under both a Yule and Uniform model.
AB  - The topology or shape of evolutionary trees and their unbalanced nature has been
      a long standing area of interest in the field of phylogenetics. Coevolutionary
      analysis, which considers the evolutionary relationships between a pair of
      phylogenetic trees, has to date not considered leveraging this unbalanced nature
      as a means to reduce the complexity of coevolutionary analysis. In this work we
      apply previous analyses of tree shapes to improve the efficiency of inferring
      coevolutionary events. In particular, we use this prior research to derive a new
      data structure for inferring coevolutionary histories. Our new data structure is
      proven to provide a reduction in the time and space required to infer
      coevolutionary events. It is integrated into an existing framework for
      coevolutionary analysis and has been validated using both synthetic and
      previously published biological data sets. This proposed data structure performs
      twice as fast as algorithms implemented using existing data structures with no
      degradation in the algorithm's accuracy. As the coevolutionary data sets increase
      in size so too does the running time reduction provided by the newly proposed
      data structure. This is due to our data structure offering a logarithmic time and
      space complexity improvement. As a result, the proposed update to existing
      coevolutionary analysis algorithms outlined herein should enable the inference of
      larger coevolutionary systems in the future. 

PMID- 25861916
TI  - Tramadol and the risk of fracture in an elderly female population: a cost utility
      assessment with comparison to transdermal buprenorphine.
AB  - INTRODUCTION: Opioid treatment for chronic pain is a known risk factor for falls
      and/or fractures in elderly patients. The latter cause a significant cost to the
      National Health Service and the Personal Social Services in the UK. Tramadol has
      a higher risk of fractures than some other opioid analgesics used to treat
      moderate-to-severe pain and, in the model described here, we investigate the cost
      effectiveness of transdermal buprenorphine treatment compared with tramadol in a
      high-risk population. METHODS: A model was developed to assess the cost
      effectiveness of tramadol compared with transdermal buprenorphine over a 1-year
      time horizon and a patient population of high-risk patients (female patients age
      75 or older). To estimate the total cost and quality-adjusted life years (QALYs)
      of treatment, published odds ratios are used in combination with the published
      incidence rates of four types of fracture: hip, wrist, humerus and other.
      RESULTS: The model shows tramadol to be associated with 1,058 more fractures per
      100,000 patients per year compared with transdermal buprenorphine, resulting in
      transdermal buprenorphine being cost-effective with an incremental cost
      effectiveness ratio of less than L7,000 compared with tramadol. Sensitivity
      analysis found this result to be robust. LIMITATIONS: In the UK data, there is
      uncertainty regarding the transdermal buprenorphine odds ratios for fractures.
      Odds ratios published in Danish and Swedish studies show similar point estimates
      but are associated with less uncertainty. CONCLUSION: Transdermal buprenorphine
      is cost-effective compared to tramadol at a willingness-to-pay threshold of
      L20,000 per QALY.

PMID- 25861918
TI  - Follow-Up of Metal-on-Metal Hip Arthroplasty Patients Is Currently Not Evidence
      Based or Cost Effective.
AB  - Over one-million patients worldwide have received metal-on-metal (MoM) hip
      arthroplasties with a significant proportion requiring revision surgery in the
      short-term for adverse reaction to metal debris (ARMD). Worldwide authorities
      have subsequently issued follow-up guidance for MoM hip patients. This article
      compares follow-up guidelines for MoM hips published by five worldwide
      authorities, analyses these protocols in relation to published evidence, and
      assesses the financial implications of these guidelines. A number of major
      differences exist between authorities regarding patient follow-up, with vast cost
      differences between protocols (L84 to L988/patient/year for stemmed MoM hips and
      L0 to L988/patient/year for hip resurfacing). Current worldwide guidance is
      neither evidence-based nor financially sustainable with most protocols lacking
      the sensitivity to detect asymptomatic ARMD lesions. 

PMID- 25861919
TI  - The Accuracy of Single Photon Emission Computed Tomography/Computed Tomography
      Arthrography in Evaluating Aseptic Loosening of Hip and Knee Prostheses.
AB  - Aseptic loosening represents the most common complication associated with hip and
      knee arthroplasty and is a common indication for surgical revision in the post
      arthroplasty population. The optimal imaging methodology in evaluating clinical
      suspected loosening is not well-defined. Our study retrospectively evaluated
      nuclear medicine arthrography with hybrid single photon emission computed
      tomography/computed tomography (SPECT/CT) in 38 patients (21 hip, 17 knee)
      compared with reference standards of surgical evaluation, spontaneous resolution
      of symptoms without revision, or a minimum of 1 year clinical and radiographic
      follow-up. Our study demonstrated a sensitivity of 100%, specificity of 96.0%,
      PPV of 92.9%, NPV of 100%, and accuracy of 97.4% with this imaging technique
      suggesting utility of nuclear medicine arthrography with SPECT/CT in the clinical
      evaluation of suspected aseptic loosening.

PMID- 25861920
TI  - Does Implant Design Influence the Accuracy of Patient Specific Instrumentation in
      Total Knee Arthroplasty?
AB  - PSI software adjusts preoperative planning to accommodate differences in implant
      design. Such adjustments may influence the accuracy of intraoperative jig
      placement, bone resection, or component placement. Our purpose was to determine
      whether implant design influences PSI accuracy. 96 and 123 PSI TKA were performed
      by a single surgeon using two different implant systems and identical PSI
      software. Femoral coronal alignment outliers were greater for Implant 1 (23.9%
      Implant 1 vs. 13.4% Implant 2; P=0.050). Tibial coronal alignment outliers were
      greater for Implant 2 (10.9% Implant 1 vs. 22.7% Implant 2; P=0.025). There was
      no difference in overall mechanical axes. Differences in implant design can
      influence bone resection and component alignment. PSI software rationale must
      align with surgeons' intraoperative goals. 

PMID- 25861921
TI  - Characterization of metabolically unhealthy normal-weight individuals: Risk
      factors and their associations with type 2 diabetes.
AB  - OBJECTIVE: A proportion of type 2 diabetes cases arise from normal-weight
      individuals who can therefore be considered to be "metabolically unhealthy normal
      weight" (MUH-NW). It remains unclear which factors account for this access risk.
      Our aims were to identify risk factors for type 2 diabetes in normal-weight
      individuals and to compare the strengths of their associations with type 2
      diabetes to that observed in overweight and obese participants. METHODS: A case
      cohort, including 2027 sub-cohort participants and 706 incident type 2 cases, was
      designed within the population-based European Prospective Investigation into
      Cancer and Nutrition Potsdam study. Adjusted means and relative frequencies of
      anthropometric, lifestyle and biochemical risk factors were calculated in groups
      stratified by BMI and incident diabetes status. Cox regressions were applied to
      evaluate associations between these variables and diabetes risk stratified by BMI
      category. RESULTS: MUH-NW individuals were characterized by known diabetes risk
      factors, e.g. they were significantly more likely to be male, former smokers,
      hypertensive, and less physically active compared to normal-weight individuals
      without incident diabetes. Higher waist circumference (women: 75.5 vs. 73.1cm;
      men: 88.0 vs. 85.1cm), higher HbA1c (6.1 vs. 5.3%), higher triglycerides (1.47
      vs. 1.11 mmol/l), and higher levels of high sensitive C-reactive protein (0.81
      vs. 0.51 mg/l) as well as lower levels of HDL-cholesterol (1.28 vs. 1.49 mmol/l)
      and adiponectin (6.32 vs. 8.25 MUg/ml) characterized this phenotype. Stronger
      associations with diabetes among normal-weight participants compared to
      overweight and obese (p for interaction<0.05) were observed for height, waist
      circumference, former smoking, and hypertension. CONCLUSIONS: Normal-weight
      individuals who develop diabetes have higher levels of diabetes risk factors,
      however, frequently still among the normal range. Still, hypertension, elevated
      HbA1c and lifestyle risk factors might be useful indicators of risk.

PMID- 25861922
TI  - Heavy path mining of protein-protein associations in the malaria parasite.
AB  - Annotating and understanding the function of proteins and other elements in a
      genome can be difficult in the absence of a well-studied and evolutionarily close
      relative. The causative agent of malaria, one of the oldest and most deadly
      global infectious diseases, is a good example of this problem. The burden of
      malaria is huge and there is a pressing need for new, more effective antimalarial
      strategies. However, techniques such as homology-dependent annotation transfer
      are severely impaired in this parasite because there are no well-understood close
      relatives. To circumvent this approach we developed a network-based method that
      uses a heavy path network-mining algorithm. We uncovered the protein-protein
      associations that are implicated in important cellular processes including genome
      integrity, DNA repair, transcriptional regulation, invasion, and pathogenesis,
      thus demonstrating the utility of this method. The URL of the source code for
      super-sequence mining method is http://www.cs.utsa.edu/~korkmaz/research/heavy
      path-mining/. 

PMID- 25861923
TI  - Antifungal therapeutic drug monitoring: when, how, and why.

PMID- 25861924
TI  - [Pulmonary mass in a patient with human immunodeficiency virus infection].

PMID- 25861925
TI  - Thyroid follicular lesions induced by thiazole-Zn feed treatment for one year in
      Sprague-Dawley rats.
AB  - Thiazole-Zn is a newly created Chinese systemic fungicide that is a thiadiazole
      compound. The toxicity of thiazole-Zn was examined in Sprague-Dawley rats fed
      diets containing 0, 4, 20 and 100mg/kg thiazole-Zn for one year. Lower body
      weight gains were noted in both males and females of the 100mg/kg diet group.
      Moreover, we show that the toxicity of thiazole-Zn was low, as evidenced by the
      absence of toxicologically significant changes in the general condition and
      appearance, hematology and clinical chemistry parameters, organ weights and
      necropsy findings of the rats. Thyroid follicular cell hyperplasia was the only
      finding of potential significance. The incidence of thyroid follicular cell
      hyperplasia significantly increased in high-dose males (4/10) and females (3/10)
      at the 26-week interim examination; one follicular adenoma in the thyroid was
      observed in high-dose males. At 52 weeks, the incidence of thyroid follicular
      cell hyperplasia was significantly higher in high-dose males (4/10) and females
      (4/10) than in the controls. Two thyroid follicular adenomas were observed in
      high-dose males. Other treatment-related effects and tumors at other sites were
      not observed. This study suggests that thiazole-Zn is a thyroid disrupter and
      likely a rat thyroid carcinogen. 

PMID- 25861926
TI  - Molecular epidemiology of Bordetella pertussis in the Philippines in 2012-2014.
AB  - OBJECTIVES: The present study was designed to determine the genotypes of
      circulating Bordetella pertussis in the Philippines by direct molecular typing of
      clinical specimens. METHODS: Nasopharyngeal swabs (NPSs) were collected from 50
      children hospitalized with pertussis in three hospitals during 2012-2014.
      Multilocus variable-number tandem repeat analysis (MLVA) was performed on the DNA
      extracts from NPSs. B. pertussis virulence-associated allelic genes (ptxA, prn,
      and fim3) and the pertussis toxin promoter, ptxP, were also investigated by DNA
      sequence-based typing. RESULTS: Twenty-six DNA extracts yielded a complete MLVA
      profile, which were sorted into 10 MLVA types. MLVA type 34 (MT34), which is rare
      in Australia, Europe, Japan, and the USA, was the predominant strain (50%). Seven
      MTs (MT29, MT32, MT33, and MT283-286, total 42%) were single-locus variants of
      MT34, while two (MT141 and MT287, total 8%) were double-locus variants of MT34.
      All MTs had the combination of virulence-associated allelic genes, ptxP1-ptxA1
      prn1-fim3A. CONCLUSIONS: The B. pertussis population in the Philippines comprises
      genetically related strains. These strains are markedly different from those
      found in patients from other countries where acellular pertussis vaccines are
      used. The differences in vaccine types between these other countries and the
      Philippines, where the whole-cell vaccine is still used, may select for distinct
      populations of B. pertussis.

PMID- 25861927
TI  - The immortal challenge.
AB  - Reproducibility in life science is a hot button topic at the moment. Jeffrey
      Perkel examines the ways in which stem cell researchers are dealing with this
      issue in their work. 

PMID- 25861928
TI  - CRISPR/Cas9 nuclease cleavage combined with Gibson assembly for seamless cloning.
AB  - Restriction enzymes have two major limitations for cloning: they cannot cleave at
      any desired location in a DNA sequence and may not cleave uniquely within a DNA
      sequence. In contrast, the clustered regularly interspaced short palindromic
      repeat (CRISPR)-associated enzyme 9 (Cas9), when coupled with single guide RNAs
      (sgRNA), has been used in vivo to cleave the genomes of many species at a single
      site, enabling generation of mutated cell lines and animals. The Cas9/sgRNA
      complex recognizes a 17-20 base target site, which can be of any sequence as long
      as it is located 5' of the protospacer adjacent motif (PAM; sequence 5'-NRG,
      where R = G or A). Thus, it can be programmed to cleave almost anywhere with a
      stringency higher than that of one cleavage in a sequence of human genome size.
      Here, the Cas9 enzyme and a specific sgRNA were used to linearize a 22 kb plasmid
      in vitro. A DNA fragment was then inserted into the linearized vector seamlessly
      through Gibson assembly. Our technique can be used to directly, and seamlessly,
      clone fragments into vectors of any size as well as to modify existing constructs
      where no other methods are available. 

PMID- 25861929
TI  - Use of pressure cycling technology for cell lysis and recovery of bacterial and
      fungal communities from soil.
AB  - Selection of cell lysis methodology is critical to microbial community analyses
      due to the inability of any single extraction technology to recover the absolute
      genetic structure from environmental samples. Numerous methodologies are
      currently applied to interrogate soil communities, each with its own inherent
      bias. Here we compared the efficacy and bias of three physical cell lysis methods
      in conjunction with the PowerLyzer PowerSoil DNA Isolation Kit (MO BIO) for
      direct DNA extraction from soil: bead-beating, vortex disruption, and hydrostatic
      pressure cycling technology (PCT). PCT lysis, which is relatively new to soil DNA
      extraction, was optimized for soils of two different textures prior to comparison
      with traditional bead-beating and vortex disruption lysis. All cell lysis methods
      successfully recovered DNA. Although the two traditional mechanical lysis methods
      yielded greater genomic, bacterial, and fungal DNA per gram soil than the PCT
      method, the latter resulted in a greater number of unique terminal restriction
      fragments by terminal RFLP (T-RFLP) analysis. These findings indicate the
      importance of diversity and quantity measures when assessing DNA extraction bias,
      as soil DNA retrieved by PCT lysis represented populations not found using
      traditional mechanical lysis methods. 

PMID- 25861930
TI  - Transmission electron microscopy sample preparation protocols for the
      ultrastructural study of cysts of free-living protozoa.
AB  - Cysts of free-living protozoa have an impact on the ecology and epidemiology of
      bacteria because they may act as a transmission vector or shelter the bacteria
      against hash environmental conditions. Detection and localization of intracystic
      bacteria and examination of the en- and excystment dynamics is a major challenge
      because no detailed protocols for ultrastructural analysis of cysts are currently
      available. Transmission electron microscopy (TEM) is ideally suited for those
      analyses; however, conventional TEM protocols are not satisfactory for cysts of
      free-living protozoa. Here we report on the design and testing of four protocols
      for TEM sample preparation of cysts. Two protocols, one based on chemical
      fixation in coated well plates and one on high-pressure freezing, were selected
      as the most effective for TEM-based ultrastructural studies of cysts. Our
      protocols will enable improved analysis of cyst structure and a better
      understanding of bacterial survival mechanisms in cysts. 

PMID- 25861931
TI  - Shining a light on LAMP assays--a comparison of LAMP visualization methods
      including the novel use of berberine.
AB  - The need for simple and effective assays for detecting nucleic acids by
      isothermal amplification reactions has led to a great variety of end point and
      real-time monitoring methods. Here we tested direct and indirect methods to
      visualize the amplification of potato spindle tuber viroid (PSTVd) by loop
      mediated isothermal amplification (LAMP) and compared features important for one
      pot in-field applications. We compared the performance of magnesium
      pyrophosphate, hydroxynaphthol blue (HNB), calcein, SYBR Green I, EvaGreen, and
      berberine. All assays could be used to distinguish between positive and negative
      samples in visible or UV light. Precipitation of magnesium-pyrophosphate resulted
      in a turbid reaction solution. The use of HNB resulted in a color change from
      violet to blue, whereas calcein induced a change from orange to yellow-green. We
      also investigated berberine as a nucleic acid-specific dye that emits a
      fluorescence signal under UV light after a positive LAMP reaction. It has a
      comparable sensitivity to SYBR Green I and EvaGreen. Based on our results, an
      optimal detection method can be chosen easily for isothermal real-time or end
      point screening applications. 

PMID- 25861932
TI  - Comparative analysis of T4 DNA ligases and DNA polymerases used in chromosome
      conformation capture assays.
AB  - Three-dimensional (3-D) genome organization in the nuclear space affects various
      genomic functions. Circular chromosome conformation capture (4C-seq) is a
      powerful technique that allows researchers to measure long-range chromosomal
      interactions with a locus of interest across the entire genome. This method
      relies on enzymatic cleavage of cross-linked chromatin and consecutive ligation
      to create ligation junctions between physically adjacent loci, followed by PCR
      amplification of locus-specific associating loci. The enzymes used must meet 4C
      standards because variations in their efficiency and performance may affect the
      quality of the obtained data. Here we systematically compare the efficiency and
      reliability of different T4 DNA ligases and PCR DNA polymerases, assessing the
      most critical and technically challenging steps in 4C. The results of this
      analysis enable the use of cost-effective enzymes with superior specificity and
      efficiency for 4C and save time in screening for appropriate primers. This
      information provides users with flexibility in their experimental design and
      guidelines for adapting and testing any enzyme of choice for obtaining
      standardized results. 

PMID- 25861933
TI  - Improved transposon-based library preparation for the Ion Torrent platform.
AB  - A transposon-based approach for the construction of sequencing libraries is an
      efficient way of preparing samples for processing on both Illumina and Ion
      Torrent platforms. However, PCR-mediated incorporation of adaptors in tagged DNA
      fragments leaves behind self-complementary regions flanking the DNA fragment.
      These regions are capable of forming hairpin structures and, together with
      adaptors, create conditions for the potential formation of template
      heteroduplexes. These negatively affect the sequencing process on the Ion Torrent
      platform and can lead to a more than 3-fold decline in output data compared with
      sequencing of conventional libraries. To address this problem, we have developed
      MuPlus, a transposon-based protocol for barcoded library preparation for Ion
      Torrent, in which one adaptor is integrated by PCR and the second is integrated
      by ligation as a single-stranded oligonucleotide after enzymatic cleavage of a
      complementary part on one strand of the tag. The resulting library does not
      contain self-complementary, hairpin-forming regions, is free of heteroduplexes,
      and can be analyzed on the Ion Torrent platform with the same efficiency as a
      library created with a ligation-based protocol. 

PMID- 25861934
TI  - Anxiolytic-like effects of ursolic acid in mice.
AB  - Ursolic acid is a pentacyclic triterpenoid that possesses several biological and
      neuropharmacological effects including antidepressant-like activity. Anxiety
      disorders represent common and disability psychiatric conditions that are often
      associated with depressive symptoms. This work investigated the anxiolytic-like
      effects of ursolic acid administration in different behavioral paradigms that
      evaluate anxiety in mice: open field test, elevated plus maze test, light/dark
      box test and marble burying test. To this end, mice were administered with
      ursolic acid (0.1, 1 and 10mg/kg, p.o.) or diazepam (2mg/kg, p.o.), positive
      control, and submitted to the behavioral tests. The results show that ursolic
      acid (10mg/kg) elicited an anxiolytic-like effect observed by the increased total
      time in the center and decreased number of rearings responses in the open field
      test and an increased percentage of entries and total time spent in the open arms
      of elevated plus maze, similarly to diazepam. No significant effects of ursolic
      acid were shown in the light/dark box and marble burying test. These data
      indicate that ursolic acid exhibits anxiolytic-like effects in the open field and
      elevated plus maze test, but not in the light/dark box and marble burying test,
      showing the relevance of testing several behavioral paradigms in the evaluation
      of anxiolytic-like actions. Of note, the results extend the understanding on the
      effects of ursolic acid in the central nervous system and suggest that it may be
      a novel approach for the management of anxiety-related disorders. 

PMID- 25861935
TI  - Comparison of mechanisms of allodynia induced by acromelic acid A between early
      and late phases.
AB  - We previously showed that intrathecal administration of acromelic acid A (ACRO-A)
      provoked tactile allodynia in mice. As well, recent studies have demonstrated
      that the activation of NMDA glutamate receptor-neuronal nitric oxide synthase
      (nNOS) pathway and glia play crucial roles in the development and maintenance of
      neuropathic pain. In order to clarify their involvement in ACRO-A-induced
      allodynia, we investigated the effects of various agents on two mouse models at
      early and late-phase allodynia. The agents employed were Ca(2+) channel
      alpha2delta ligands, NMDA and AMPA receptor antagonists, nNOS, and
      Ca(2+)/calmodulin kinase II inhibitors. When injected simultaneously with ACRO-A,
      all of these agents blocked allodynia in the early-phase group; however, they did
      not block allodynia when injected 7 days after the administration of ACRO-A in
      the late-phase group. In order to block glial activation, astrocytic inhibitor L
      alpha-aminoadipate (LAA) or microglial inhibitor minocycline was administrated,
      and allodynia was examined on day 7. Activations of nNOS and glia in the spinal
      cord were histochemically examined at 1 h or 1 week after injection of ACRO-A. We
      found that nNOS activity increased 1 h after ACRO-A injection; however, it did
      not increase 1 week after ACRO-A injection. Conversely, microglial activation was
      observed 1 week after ACRO-A injection and was significantly inhibited with
      minocycline treatment. Moreover, only LAA was found to inhibit late-phase
      allodynia. In this study, we demonstrate that NMDA receptor activation is
      involved only in ACRO-A-induced tactile allodynia in the early phase, and that
      spinal astrocytic activation contributes to allodynia in the late phase.

PMID- 25861936
TI  - Involvement of beta3-adrenoceptors in the inhibitory control of cholinergic
      activity in human bladder: Direct evidence by [(3)H]-acetylcholine release
      experiments in the isolated detrusor.
AB  - Bladder overactivity (OAB) is a multifactorial bladder disorder that requires
      therapeutics superior to the current pharmacological treatment with muscarinic
      antagonists. beta3-adrenoceptor (beta3-ADR) agonists represent a novel promising
      approach that differently addresses the parasympathetic pathway, but the clinical
      efficacy of these drugs has not been fully elucidated to date. Therefore, we
      aimed to study the pharmacological mechanisms activated by beta3-ADR agonists at
      muscular and neural sites in the isolated human bladder. Detrusor smooth muscle
      strips obtained from male patients undergoing total cystectomy were labelled with
      tritiated choline and stimulated with electrical field stimulation (EFS). EFS
      produced smooth muscle contraction and simultaneous acetylcholine ([(3)H]-ACh)
      release, which mostly reflects the neural origin of acetylcholine. Isoprenaline
      (INA), BRL37344 and mirabegron inhibited the EFS-evoked contraction and [(3)H]
      ACh release in a concentration-dependent manner, yielding concentration-response
      curves (CRCs) that were shifted to the right by the selective beta3-ADR
      antagonists L-748,337 and SR59230A. Based on the agonist potency estimates
      (pEC50) and apparent affinities (pKb) of antagonists evaluated from the CRCs of
      agonists, our data confirm the occurrence of beta3-ADRs at muscle sites.
      Moreover, our data are consistent with the presence of inhibitory beta3-ADRs that
      are functionally expressed at the neural site. Taken together, these findings
      elucidate the mechanisms activated by beta3-ADR agonists because neural beta3
      ADRs participate in the inhibition of detrusor motor drive by reducing the amount
      of acetylcholine involved in the cholinergic pathway. 

PMID- 25861937
TI  - The therapeutic potential of berberine against the altered intrinsic properties
      of the CA1 neurons induced by Abeta neurotoxicity.
AB  - It was demonstrated that treatment with beta amyloid (Abeta) led to extreme
      alterations in the intrinsic electrophysiological properties of CA1 pyramidal
      neurons. Also, malfunction of the cholinergic system is correlated to the memory
      and cognitive impairments. Several new studies have suggested that Berberis
      vulgaris can act as a cholinesterase inhibitor. The present study aimed to
      investigate the effects of berberine (BER) on the Abeta-induced impairments in
      learning and memory. The male Wistar rats were divided into 4 groups of Sham,
      BER, Abeta and Abeta+BER. The administration of BER or its vehicle started
      immediately after the injection of Abeta and followed by 13 days. Then, the
      animals were tested for learning and memory performance using the Morris water
      maze (MWM) and passive avoidance tests. Then, they were sacrificed for the whole
      cell patch clamp recording. The results of the MWM and passive avoidance tasks
      indicated that administration of the BER in the Abeta+BER group prevented the
      memory impairment induced by Abeta. The results of the whole cell patch clamp
      also showed that administration of the BER restored the Abeta-induced impairments
      in the firing frequency, half-width and rebound action potential. These results
      suggested that administration of the BER could ameliorate neurotoxicity induced
      by Abeta. However, this neuroprotection impact could be resulted from the balance
      effect of the Ca(2+) entry. The optimal level of Ca(2+) entry by BER could be a
      major factor that modified the function of the Ca(2+)-activated K(+) channels and
      decreased the half-width in the Abeta treated rats. 

PMID- 25861938
TI  - Essential oil based polymeric patch development and evaluating its repellent
      activity against mosquitoes.
AB  - Essential oil based insect repellents are environment friendly and provide
      dependable personal protection against the bites of mosquitoes and other blood
      sucking insects. In the present study, optimized mixture of three essential oils
      was embedded into the ethylcellulose (EC) and polyvinylpyrrolidone (PVP K-30)
      polymers to develop essential oils based patch type mosquito repellent
      formulation. The developed formulation was characterized for various physico
      chemical properties, oil release efficiency and essential oil-polymer
      interaction. Repellent activity of the formulation was evaluated against Ae. (S)
      albopictus mosquitoes and compared with commercially available synthetic
      insecticide based mosquito repellent cream Odomos((r)) in the laboratory. The
      developed patches were 100% flat and there was no interaction between oil
      components and the excipients. Patches were smooth, homogenous and provided
      excellent mosquito repellent activity comparable to Odomos((r)) under laboratory
      condition. Morphological and physico-chemical characterization indicated that the
      formulation was stable and suitable with the polymeric combination. The patch
      formulation did not show any inhalation toxicity in experimental Wistar rat. The
      repellent patches developed and evaluated currently, may provide a suitable, eco
      friendly, acceptable and safe alternative to the existing synthetic repellent
      formulations for achieving protection against mosquitoes.

PMID- 25861939
TI  - Placental malaria and modulation of immune and hormonal responses in Cameroonian
      women.
AB  - Adverse pregnancy outcomes place the lives of mother and new born babies in
      jeopardy, especially in Sub Saharan Africa. Although a well-balanced network of
      the pregnancy-associated hormones and lipid fractions is necessary for healthy
      pregnancy, the profiles of some of these biomarkers alongside those of some
      cytokines in relation to placental malaria (PM) and poor pregnancy outcomes are
      unknown. Therefore between 2013 and 2014, paired peripheral and placental blood
      samples were collected from 135 Cameroonian women at delivery. Parasitaemia was
      determined microscopically and haemoglobin levels using Coulter counter. Plasma
      levels of cytokines (IFN-gamma, IL-1beta and IL-7) and pregnancy-associated
      hormones (17beta oestradiol and progesterone) were measured by ELISA and the
      levels of lipid fractions: total cholesterol (TC), high-density lipoprotein
      cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and
      triglycerides (TG) determined by Colorimetric enzymatic methods. Parasitaemia was
      inversely related to parity, haemoglobin levels and birth weight (P<=0.019).
      While the levels of IFN-gamma and cholesterol (total, HDL and LDL) were higher in
      peripheral plasma, those of IL-1beta, 17beta oestradiol, progesterone and
      triglyceride were higher in placental blood (P<0.001). Absence of PM was
      significantly associated with high plasma levels of IFN-gamma, IL-7 and HDL-C and
      low plasma levels of 17beta oestradiol and TG. Moreover, IL-7 levels correlated
      positively and significantly with haemoglobin levels and with both peripheral and
      placental levels of progesterone. Baby birth weight increased with plasma levels
      of progesterone and HDL-C. Levels of IFN-gamma correlated positively and
      significantly with HDL-C, but negatively with LDL-C; thus, might prevent pregnant
      women from atherogenic risk. Study of the inter-relationship between hormones,
      cytokines and lipids revealed that the association between IL-7 and progesterone
      and/or some lipid fractions followed inverse trends from that of IFN-gamma. These
      results suggest that in PM, IFN-gamma and IL-7 might protect against poor
      pregnancy outcomes, which decrease plasma levels of progesterone, maternal
      haemoglobin and HDL-C, leading to low birth weight. However, these cytokines may
      act differently with regards to progesterone and some lipid fractions. PM may
      also lower plasma levels of HDL-C and increase that of TG which is the most
      important risk factor for cardiovascular disorders and consequently poor
      pregnancy outcomes. 

PMID- 25861941
TI  - Surgical preparation of mice for recording cardiorespiratory parameters in vivo.
AB  - BACKGROUND: The explosion in the use of genetically modified mouse strains to
      investigate function in biology has an enormous potential to expand on
      pharmacological studies traditionally conducted in rats. A key limitation to date
      is the inability to record from multiple nerves in an anaesthetised mouse for
      long periods. NEW METHOD: Here we describe an in vivo preparation that maintains
      mice in a suitable physiological state, under anaesthesia, for at least 6 hr and
      also enables multiple cardiorespiratory recordings over that time. RESULTS: Using
      the method described, blood pressure, heart rate, phrenic nerve activity,
      splanchnic nerve activity and heart rate were able to be recorded for hours in an
      anaesthetised, paralysed and mechanically ventilated mouse. COMPARISON WITH
      EXISTING METHOD: Existing anaesthetised mouse preparations are limited by
      difficulties in maintaining mice under anaesthesia for long periods. This time
      constraint therefore limits the surgical time and number of cardiorespiratory
      variables recorded. It also limits the type of stimuli that can be administered
      and the length of recorded responses. The method described here optimises these
      variables to overcome these challenges. CONCLUSIONS: In summary, we report an
      approach that enables physiological and pharmacological studies previously
      undertaken in larger animals or 'reduced' preparations, to be conducted in vivo
      in mice. We anticipate that the use of this preparation will enable a deeper
      understanding of genetic variation, and allow a much greater level of phenotypic
      characterisation in genetically modified mice.

PMID- 25861942
TI  - A study of event related potential frequency domain coherency using multichannel
      electroencephalogram subspace analysis.
AB  - BACKGROUND: Event related potentials (ERP) are time-locked electrical activities
      of the brain in direct response to a specific sensory, cognitive, or motor
      stimulus. ERP components, such as the P300 wave, which are involved in the
      process of decision-making, help scientists diagnose specific cognitive
      disabilities. NEW METHOD: In this study, we utilize the angles between
      multichannel electroencephalogram (EEG) subspaces in different frequency bands,
      as a similarity factor for studying the spatial coherency between ERP frequency
      responses. A matched filter is used to enhance the ERP from background EEG.
      RESULTS: While previous researches have focused on frequencies below 10 Hz, as
      the major frequency band of ERP, it is shown that by using the proposed method,
      significant ERP-related information can also be found in the 25-40 Hz band. These
      frequency bands are selected by calculating the correlation coefficient between
      P300 response segments and synthetic EEG, and ERP segments without P300 waves,
      and by rejecting the bands having the most association with background EEG and
      non-P300 components. COMPARISON WITH EXISTING METHODS: The significance of the
      results is assessed by real EEG acquired in brain computer interface experiments
      versus synthetic EEG produced by existing methods in the literature, to assure
      that the results are not systematic side effects of the proposed framework.
      CONCLUSIONS: The overall results show that the equivalent dipoles corresponding
      to narrow-band events in the brain are spatially coherent within different (not
      necessarily adjacent) frequency bands. The results of this study can lead into
      novel perspectives in ERP studies.

PMID- 25861940
TI  - Neurohormetic phytochemicals: An evolutionary-bioenergetic perspective.
AB  - The impact of dietary factors on brain health and vulnerability to disease is
      increasingly appreciated. The results of epidemiological studies, and
      intervention trials in animal models suggest that diets rich in phytochemicals
      can enhance neuroplasticity and resistance to neurodegeneration. Here we describe
      how interactions of plants and animals during their co-evolution, and resulting
      reciprocal adaptations, have shaped the remarkable characteristics of
      phytochemicals and their effects on the physiology of animal cells in general,
      and neurons in particular. Survival advantages were conferred upon plants capable
      of producing noxious bitter-tasting chemicals, and on animals able to tolerate
      the phytochemicals and consume the plants as an energy source. The remarkably
      diverse array of phytochemicals present in modern fruits, vegetables spices, tea
      and coffee may have arisen, in part, from the acquisition of adaptive cellular
      stress responses and detoxification enzymes in animals that enabled them to
      consume plants containing potentially toxic chemicals. Interestingly, some of the
      same adaptive stress response mechanisms that protect neurons against noxious
      phytochemicals are also activated by dietary energy restriction and vigorous
      physical exertion, two environmental challenges that shaped brain evolution. In
      this perspective article, we describe some of the signaling pathways relevant to
      cellular energy metabolism that are modulated by 'neurohormetic phytochemicals'
      (potentially toxic chemicals produced by plants that have beneficial effects on
      animals when consumed in moderate amounts). We highlight the cellular
      bioenergetics-related sirtuin, adenosine monophosphate activated protein kinase
      (AMPK), mammalian target of rapamycin (mTOR) and insulin-like growth factor 1
      (IGF-1) pathways. The inclusion of dietary neurohormetic phytochemicals in an
      overall program for brain health that also includes exercise and energy
      restriction may find applications in the prevention and treatment of a range of
      neurological disorders. 

PMID- 25861943
TI  - Burden of substance use disorders, mental illness, and correlates of infectious
      diseases among soon-to-be released prisoners in Azerbaijan.
AB  - BACKGROUND: Despite low HIV prevalence in the South Caucasus region, transmission
      is volatile. Little data are available from this region about addiction and
      infectious diseases among prisoners who transition back to communities. METHODS:
      A nation-wide randomly sampled biobehavioral health survey was conducted in 13
      non-specialty Azerbaijani prisons among soon-to-be-released prisoners. After
      informed consent, participants underwent standardized health assessment surveys
      and testing for HIV, hepatitis B and C, and syphilis. RESULTS: Of the 510
      participants (mean age = 38.2 years), 11.4% were female, and 31.9% reported pre
      incarceration drug injection, primarily of heroin. Prevalence of HCV (38.2%), HIV
      (3.7%), syphilis (3.7%), and HBV (2.7%) was high. Among the 19 HIV-infected
      inmates, 14 (73.7%) were aware of their HIV status, 12 (63.2%) were receiving
      antiretroviral therapy (ART), and 5 (26.3%) had CD4 < 350 cells/mL (4 of these
      were on ART). While drug injection was the most significant independent correlate
      of HCV (AOR = 12.9; p = 0.001) and a significant correlate of HIV (AOR = 8.2; p =
      0.001), both unprotected sex (AOR = 3.31; p = 0.049) and working in
      Russia/Ukraine (AOR = 4.58; p = 0.008) were also correlated with HIV. CONCLUSION:
      HIV and HCV epidemics are concentrated among people who inject drugs (PWIDs) in
      Azerbaijan, and magnified among prisoners. A transitioning HIV epidemic is
      emerging from migration from high endemic countries and heterosexual risk. The
      high diagnostic rate and ART coverage among Azerbaijani prisoners provides new
      evidence that HIV treatment as prevention in former Soviet Union (FSU) countries
      is attainable, and provides new insights for HCV diagnosis and treatment as new
      medications become available. Within prison evidence-based addiction treatments
      with linkage to community care are urgently needed.

PMID- 25861944
TI  - A comprehensive review of the effects of mixing caffeinated energy drinks with
      alcohol.
AB  - BACKGROUND: In response to concern about whether mixing caffeinated energy drinks
      with alcohol (AED) increases alcohol consumption and related harm, and the role
      of industry in this debate, we conducted a comprehensive review of the research
      evidence on the effects of AED and documented industry involvement in this
      research. METHOD: A systematic review of 6 databases. Studies must have examined
      the effect of consuming alcohol with energy drinks (ED) or caffeine on alcohol
      related outcomes. RESULTS: 62 studies were identified; 29 were experiments, 9 had
      industry ties (8 with Red Bull GmbH). Young adults who consumed AED drank more
      alcohol and experienced more alcohol-related harm than other drinkers. There was
      insufficient evidence to conclude that AED led to increased alcohol consumption
      or altered the nature of alcohol-related harm. However, AED consumers reported
      that AED increased stimulation and alertness, offset fatigue from drinking, and
      facilitated drinking. Experimental research also found that combining ED or
      caffeine with alcohol increased stimulation and alertness, offset alcohol-related
      fatigue and increased the desire to keep drinking. It did not change BAC,
      perceived intoxication, perceived impairment and it did not reverse alcohol
      induced impairment on simple psychomotor tasks. Combining ED/caffeine with
      alcohol reduced alcohol-induced impairment on some but not all aspects of complex
      tasks. Although few in number, studies with industry ties presented contrary
      evidence. CONCLUSION: A growing body of evidence suggests that AED may facilitate
      drinking and related harms via its effects on intoxication but a causal link
      needs to be confirmed. The influence of industry involvement in this area of
      research needs to be monitored.

PMID- 25861946
TI  - The interrelation between sensorimotor abilities, cognitive performance and
      individual EEG alpha peak frequency in young children.
AB  - OBJECTIVE: The aim of this study was to identify the interrelation between
      sensorimotor abilities, cognitive performance and individual alpha peak frequency
      (iAPF), an EEG marker of global architectural and functional properties of the
      human brain, in healthy preschool children. METHODS: 25 participants completed a
      one minute eyes-closed EEG recording, two cognitive tests assessing processing
      speed and visual working memory and a sensorimotor test battery. RESULTS: We
      found positive correlations between selective sensorimotor abilities and iAPF;
      however, no significant correlations were observed between iAPF and cognitive
      performance. Specifically, locomotor skills correlated with iAPF across all
      cortical regions, except for the occipital cortex. Furthermore, a close
      relationship was found between sensorimotor and cognitive performance indicating
      that children with improved sensorimotor abilities were faster and/or more
      accurate in cognitive task performance. The cumulative pattern of our results
      indicates that a close relationship exists between sensorimotor and cognitive
      performance in young children. However, this relationship is dissociated from the
      iAPF. CONCLUSION: In contrast to adults, in young children the iAPF is related to
      locomotor skills and not to cognitive processing speed or visual working memory
      function. SIGNIFICANCE: The global architectural and functional properties of the
      brain are closely related to locomotor skills during development.

PMID- 25861947
TI  - Collagen-low molecular weight hyaluronic acid semi-interpenetrating network
      loaded with gelatin microspheres for cell and growth factor delivery for nucleus
      pulposus regeneration.
AB  - Intervertebral disc (IVD) degeneration is one of the main causes of low back
      pain. Current surgical treatments are complex and generally do not fully restore
      spine mobility. Development of injectable extracellular matrix-based hydrogels
      offers an opportunity for minimally invasive treatment of IVD degeneration. Here
      we analyze a specific formulation of collagen-low molecular weight hyaluronic
      acid (LMW HA) semi-interpenetrating network (semi-IPN) loaded with gelatin
      microspheres as a potential material for tissue engineering of the inner part of
      the IVD, the nucleus pulposus (NP). The material displayed a gel-like behavior,
      it was easily injectable as demonstrated by suitable tests and did not induce
      cytotoxicity or inflammation. Importantly, it supported the growth and
      chondrogenic differentiation potential of mesenchymal stem cells (MSC) and nasal
      chondrocytes (NC) in vitro and in vivo. These properties of the hydrogel were
      successfully combined with TGF-beta3 delivery by gelatin microspheres, which
      promoted the chondrogenic phenotype. Altogether, collagen-LMW HA loaded with
      gelatin microspheres represents a good candidate material for NP tissue
      engineering as it combines important rheological, functional and biological
      features. 

PMID- 25861945
TI  - Evidence of injection drug use in Kisumu, Kenya: Implications for HIV prevention.
AB  - BACKGROUND: Injection drug use is increasingly contributing to the HIV epidemic
      across sub-Saharan Africa. This paper provides the first descriptive analysis of
      injection drug use in western Kenya, where HIV prevalence is already highest in
      the nation at 15.1%. METHODS: We draw on quantitative data from a study of
      injection drug use in Kisumu, Kenya. We generated descriptive statistics on socio
      demographics, sexual characteristics, and drug-related behaviors. Logistic
      regression models were adjusted for sex to identify correlates of self-reported
      HIV positive status. RESULTS: Of 151 participants, mean age was 28.8 years, 84%
      (n = 127) were male, and overall self-reported HIV prevalence reached 19.4%.
      Women had greater than four times the odds of being HIV positive relative to men
      (Odds Ratio [OR] 4.5, CI: 1.7, 11.8, p = .003). Controlling for sex, ever
      experiencing STI symptoms (Adjusted Odds ratio [AOR] 4.6, 95% CI 1.7, 12.0, p =
      .002) and sharing needles or syringes due to lack of access (AOR 3.6, 95% CI 1.2,
      10.5, p = .02) were significantly associated with HIV positive status. Lower
      education (AOR 2.3, 95% CI 0.9, 5.6, p=.08), trading sex for drugs (AOR 2.8, 95%
      CI 0.9, 8.8, p = .08), being injected by a peddler (AOR 2.9, 95% CI 1.0, 8.5, p =
      .05), and injecting heroin (AOR 2.3, 95% CI 1.0, 5.7, p = .06), were marginally
      associated with HIV. CONCLUSIONS: This exploratory study identified patterns of
      unsafe drug injection and concurrent sexual risk in western Kenya, yet few
      resources are currently available to address addiction or injection-related harm.
      Expanded research, surveillance, and gender sensitive programming are needed.

PMID- 25861948
TI  - Focal therapy of neuroblastoma using silk films to deliver kinase and
      chemotherapeutic agents in vivo.
AB  - Current methods for treatment of high-risk neuroblastoma patients include
      surgical intervention, in addition to systemic chemotherapy. However, only
      limited therapeutic tools are available to pediatric surgeons involved in
      neuroblastoma care, so the development of intraoperative treatment modalities is
      highly desirable. This study presents a silk film library generated for focal
      therapy of neuroblastoma; these films were loaded with either the
      chemotherapeutic agent doxorubicin or the targeted drug crizotinib. Drug release
      kinetics from the silk films were fine-tuned by changing the amount and physical
      crosslinking of silk; doxorubicin loaded films were further refined by applying a
      gold nanocoating. Doxorubicin-loaded, physically crosslinked silk films showed
      the best in vitro activity and superior in vivo activity in orthotopic
      neuroblastoma studies when compared to the doxorubicin-equivalent dose
      administered intravenously. Silk films were also suitable for delivery of the
      targeted drug crizotinib, as crizotinib-loaded silk films showed an extended
      release profile and an improved response both in vitro and in vivo when compared
      to freely diffusible crizotinib. These findings, when combined with prior in vivo
      data on silk, support a viable future for silk-based anticancer drug delivery
      systems.

PMID- 25861950
TI  - A novel peptide for efficient siRNA delivery in vitro and therapeutics in vivo.
AB  - Small interfering RNA (siRNA) shows great therapeutic potential due to its
      ability to regulate gene expression in a highly selective manner. However, its
      application has been limited by ineffective cellular uptake of siRNAs. To achieve
      successful gene-silencing efficiency, a safe and effective delivery vector is
      generally required. In this study, we designed a series of amphipathic peptides
      that comprised a variant of a nuclear localization sequence, 0-6 histidine
      residues and an optional stearic acid group. Among these candidates, STR-HK
      exhibited good characteristics as a safe and efficient siRNA delivery vector,
      facilitating efficient siRNA delivery to mammalian cells without causing
      cytotoxicity. Moreover, the intratumoral injection of STR-HK/siRNA complexes
      achieved high anti-tumor activity through the downregulation of the Bcl-2 protein
      in mice, with an inhibition rate of 62.8%. Our data demonstrate that STR-HK is a
      highly promising siRNA delivery vector for therapeutic applications. 

PMID- 25861951
TI  - Use status and metabolism of realgar in Chinese patent medicine.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Realgar is widely used in combination with other
      herbs as Chinese patent medicine to treat a wide range of diseases in China. It
      is also a well known arsenical toxicant. Chronic arsenic poisoning events caused
      by long-term usage of realgar-containing medicines have been reported in
      literatures. Given to the paradoxical role of realgar, comprehensive outline of
      its usage status in Chinese patent medicine might provide basal data for
      evaluating its toxicology risks in populations. Unfortunately, the relevant
      information is limited. Also, a metabolic process after intake of realgar
      containing medicine in humans is poorly understood. MATERIALS AND METHODS: The
      Traditional Chinese Patent Medicine Prescription Database was reviewed to get the
      information on the usage status of realgar. Realgar powder was dissolved in
      different pH-value solutions (1, 3, 5, 7, 9 and 11) to determine the soluble
      arsenic concentrations from realgar. Ten volunteers aged 24-26 years old were
      recruited to take four pills of Niu Huang Jie Du Pian (NHJDP), a very common
      Chinese patent medicine with realgar, to analyze the arsenic metabolism after
      exposure to realgar-containing medicine. The four pills were taken according to
      the medical instruction. Concentrations of soluble arsenic from realgar and
      urinary arsenic metabolites in humans were determined by hydride generation
      atomic absorption spectrometry. RESULTS: A total of 191 (2.25%) realgar
      containing traditional Chinese patent medicines were obtained from the database,
      and almost 86.91% of them were for oral application. 73 (38.22%) medicines were
      found to be available for children. The mass fraction of arsenic in realgar
      containing medicine ranged from 0.11% to 27.52%. According to medical
      instructions, the amount of average daily arsenic intake ranged from 0.47 to
      2895.53mg. Nearly 86% medicines with daily intake of arsenic >10mg. Only
      inorganic arsenic (iAs) was detected from realgar in dissolution experiment and
      the levels of soluble iAs increased with pH values. After intake NHJDP, arsenic
      excretion in urine significantly increased, with a maximum excretion of iAs and
      monomethylarsonic acid at 6h post-ingestion and a peak excretion of
      dimethylarsinic acid at 9h post-ingestion. Arsenic methylation capacity was
      decreased after intake NHJDP. Females carried a more efficient arsenic
      methylation process than males. CONCLUSIONS: Realgar is widely used in
      traditional Chinese medicine. The arsenic solubility from realgar may be enhanced
      under alkaline conditions. The levels of urinary arsenic metabolites
      significantly increased while the arsenic methylation capacity significantly
      decreased after intaking realgar-containing medicine, which may suggest that a
      potential health hazard exists if people use arsenical medicines for long-term.

PMID- 25861949
TI  - Delineation of in vitro chondrogenesis of human synovial stem cells following
      preconditioning using decellularized matrix.
AB  - As a tissue-specific stem cell for chondrogenesis, synovium-derived stem cells
      (SDSCs) are a promising cell source for cartilage repair. However, a small biopsy
      can only provide a limited number of cells. Cell senescence from both in vitro
      expansion and donor age presents a big challenge for stem cell based cartilage
      regeneration. Here we found that expansion on decellularized extracellular matrix
      (dECM) full of three-dimensional nanostructured fibers provided SDSCs with unique
      surface profiles, low elasticity but large volume as well as a fibroblast-like
      shape. dECM expanded SDSCs yielded larger pellets with intensive staining of type
      II collagen and sulfated glycosaminoglycans compared to those grown on plastic
      flasks while SDSCs grown in ECM yielded 28-day pellets with minimal matrix as
      evidenced by pellet size and chondrogenic marker staining, which was confirmed by
      both biochemical data and real-time PCR data. Our results also found lower levels
      of inflammatory genes in dECM expanded SDSCs that might be responsible for
      enhanced chondrogenic differentiation. Despite an increase in type X collagen in
      chondrogenically induced cells, dECM expanded cells had significantly lower
      potential for endochondral bone formation. Wnt and MAPK signals were actively
      involved in both expansion and chondrogenic induction of dECM expanded cells.
      Since young and healthy people can be potential donors for this matrix expansion
      system and decellularization can minimize immune concerns, human SDSCs expanded
      on this future commercially available dECM could be a potential cell source for
      autologous cartilage repair.

PMID- 25861952
TI  - Antidiarrheal effect of Alpinia oxyphylla Miq. (Zingiberaceae) in experimental
      mice and its possible mechanism of action.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The fructus Alpinia oxyphylla Miq. (AOM) has been
      used for treating diarrhea with spleen deficiency and gastralgia for thousands of
      years. A number of traditional Chinese medicine formulae provide AOM as an
      alternative herbal treatment for diarrhea, but the scientific basis for this
      usage has not been well defined. AIM OF THE STUDY: In this study, we tried to
      investigate the antidiarrheal activity and possible mechanisms of Fructus AOM,
      aiming to enrich our understanding to the scientific meanings and theoretical
      significance of Fructus AOM in clinical practice. MATERIALS AND METHODS: The
      fructus of AOM collected from Hainan province in China were macerated in the 95%
      ethanol to obtain the crude 95% ethanol extract, followed by subjected to
      chromatographic separation over a Diaion HP20 column to obtain 90% and 50%
      ethanol eluted fractions. The activities of the crude extract and fractions on
      castor oil induced acute diarrhea, rhubarb induced chronic diarrhea,
      gastrointestinal transit (GIT) in mice, and contractions of isolated guinea-pig
      ileum were evaluated. Additionally, nitric oxide (NO), gastrointestinal peptides
      gastrin (GAS), motilin (MTL) and somatostatin (SS) levels that related to
      gastrointestinal motilities were detected to demonstrate the potential
      mechanisms. Ultimately, LC-MS/MS method was utilized to ensure the chemical
      consistency. RESULTS: The 95% ethanol extract and 90% ethanol eluted fraction
      significantly delayed the onset time and decreased the wet faeces proportion
      compared with control group in the castor oil induced acute diarrhea mice. In
      terms of further evaluation of antidiarrheal activity, the 95% ethanol extract
      and 90% ethanol elution displayed significant inhibition of the intestinal
      propulsion at the two highest oral doses of 20 g crude drug/kg and 1g/kg.
      Moreover the 95% ethanol extract (10 and 20 g crude drug/kg) and 90% ethanol
      elution (0.5 and 1g/kg) could significantly inhibit the GIT, which was partially
      attributed to the increase in NO and SS levels, and the decreased MTL. In vitro
      spontaneous contractions of the isolated guinea pig ileum induced by carbachol,
      neostigmine and histamine were attenuated by both the extract and elution.
      Phytochemical analysis of 95% ethanol extract and its fractions identified the
      presence of diphenylheptanes, sesquiterpenes, and flavones as the major
      components. CONCLUSIONS: Our in vivo and in vitro data could partly support and
      justify the traditional usage of Fructus AOM on the treatment of diarrhea in
      traditional medicine.

PMID- 25861953
TI  - Elephantopus scaber induces apoptosis through ROS-dependent mitochondrial
      signaling pathway in HCT116 human colorectal carcinoma cells.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Elephantopus scaber also known as Elephant's foot
      (Asteraceae family) has a plethora of traditional applications including dysuria,
      diarrhea, dysentery, leukemia and cancer. This study aimed to investigate the
      apoptosis inducing effects of E. scaber and the underlying mechanisms in HCT116
      colorectal cell line. METHODS: The MTT assay was used to determine the IC50
      values on cancer cell lines by the ethanol, hexane, ethyl acetate and water
      fractions. Apoptosis was detected by cell morphologic observation through Hoechst
      33342/PI dual staining, phosphatidylserine externalization by Annexin V/PI
      staining and DNA fragmentation by TUNEL assay. The caspase activity, Bcl-2 family
      and p53 proteins were determined by flow cytometric analysis. The cleaved PARP
      protein expression was assessed by western blot analysis RESULTS: The ethanol
      extract of E. scaber and its fractions significantly inhibited the growth of
      HCT116 and HT-29 cells and induced apoptosis. The E. scaber ethyl acetate
      fraction (ESEAF) was the most potent on HCT116 cell line with the IC50 value of
      1.42 +/- 0.10 ug/mL. The induction of apoptosis was marked by nuclear shrinkage
      accompanied with chromatin condensation, DNA fragmentation and phosphatidylserine
      externalization. The results showed that ESEAF-induced apoptosis was associated
      with an upregulation of proapoptotic Bax, elevation of Bax/Bcl-2 ratio,
      dissipation of mitochondrial membrane potential, activation of caspase-3 and
      cleavage of poly (ADP-ribose) polymerase (PARP). In addition, a compromised
      mitochondrial membrane potential and overproduction of ROS demonstrated the
      involvement of the mitochondrial signaling pathway. Mechanistic studies further
      revealed that ESEAF caused the augmentation of the intracellular ROS,
      subsequently incited the increase in p53 protein expression and led to
      oligomerization of Bax, depolarization of mitochondrial membrane potential and
      caspases cascade (caspase-3/7 and -9) in a time-dependent manner. The attenuation
      of intracellular ROS level by N-acetyl-l-cysteine (NAC) preserved the integrity
      of mitochondrial membrane and rescued the cells from cell death. Furthermore,
      caspase cascade results in the cleavage of PARP which ultimately activated DNA
      fragmentation and eventually apoptosis. CONCLUSION: Taken together, cumulative
      evidences in this study suggest that ESEAF induces apoptosis through ROS
      dependent mitochondrial signaling pathway and holds potential therapeutic effect
      for colorectal cancer.

PMID- 25861954
TI  - Anti-inflammatory effects of water extract of Taraxacum mongolicum hand.-Mazz on
      lipopolysaccharide-induced inflammation in acute lung injury by suppressing
      PI3K/Akt/mTOR signaling pathway.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Taraxacum mongolicum Hand.-Mazz is a famous
      medicinal plant in China, has been listed in the Pharmacopoeia of the People's
      Republic of China and used to treat infection, fever, upper respiratory tract
      infection, pneumonia, and other infectious diseases. This study aims to evaluate
      the possible mechanisms responsible for the anti-inflammation effects of water
      extract of T. mongolicum Hand.-Mazz (WETMHM) on lipopolysaccharide (LPS)-induced
      inflammatory in acute lung injury. MATERIALS AND METHODS: Female BALB/c mice were
      randomly divided into five groups with 10 mice in each group: (1) control group
      (saline), (2) LPS group, (3) LPS+dexamethasone (LPS+Dex, 2mg/kg, administered by
      gavage), (4) LPS+WETMHM (5 g/kg, administered by gavage), (5) LPS+WETMHM (10
      g/kg, administered by gavage). The cell counting in the bronchoalveolar lavage
      fluid (BALF) was measured. The animal lung edema degree was evaluated by wet/dry
      weight (W/D) ratio. The superoxidase dismutase (SOD) activity and myeloperoxidase
      (MPO) activity were assayed by SOD and MPO kits, respectively. The levels of
      inflammation mediators including tumor necrosis factor-alpha (TNF-alpha),
      interleukin (IL)-1beta, and IL-6 were assayed by an enzyme-linked immunosorbent
      assay method. Pathological changes of lung tissues were observed by hematoxylin
      and eosin (HE) staining. The levels of P-PI3K, PI3K, P-Akt, Akt, P-mTOR and mTOR
      were measured by Western blotting. RESULTS: The data showed that treatment with
      the WETMHM inhibited LPS-induced inflammation: (1) WETMHM attenuated inflammation
      cell numbers in the BALF, (2) decreased protein levels of lung PI3K/Akt/mTOR, and
      (3) improved SOD activity and (4) inhibited MPO activity; (5) histological
      studies demonstrated that WETMHM substantially inhibited LPS-induced neutrophils
      in lung tissue. CONCLUSION: The results indicated that the WETMHM had a
      protective effect on LPS-induced ALI in mice.

PMID- 25861955
TI  - Ethnobotanical study of Loloh: Traditional herbal drinks from Bali (Indonesia).
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Loloh are herbal drinks produced and consumed
      exclusively in Bali (Indonesia) to prevent and treat different ailments. This is
      the first study to document plants species used as Loloh, reporting the
      phytochemical components and pharmacological properties of the most cited plants.
      Documenting the plants used in herbal drinks in Bali by local communities to
      treat various ailments (providing some information on phytochemistry and
      pharmacology of the most interesting plants). MATERIALS AND METHODS:
      Ethnobotanical data were obtained through semi-structured interviews (individual
      and group discussions) and questionnaires. Plant specimens were collected,
      identified and made into herbarium vouchers. RESULTS: A total of 51 plants
      species (belonging to 32 families) have been documented for their use in the
      various preparation of Loloh. Different plants and plant parts are used to
      prepare Loloh to treat heartburn, fever, diarrhea, hypertension, aphthous
      stomatitis (canker sores), and other minor health problems. These plants are
      mainly prepared as decoctions, are juiced or simply added to the preparation. The
      most cited plants (>30 informants) are Alstonia scholaris (L.) R. Br., Blumea
      balsamifera (L.) DC., Cinnamomum burmanni Nees ex Bl., and Piper betle L. These
      plants are well studied with multiple demonstrated pharmacological activities
      (e.g., antimicrobial, anticancer, antidiabetic). CONCLUSION: The Balinese
      communities still preserve a rich ethnobotanical knowledge. Several species are
      well known for their pharmacological properties, but some [such as Pneumatopteris
      callosa (Blume) Nakai and Dendrocnide stimulans (L. f.) Chew] are understudied
      and could be promising candidates for further research.

PMID- 25861956
TI  - World Workshop on Oral Medicine VI: an international validation study of clinical
      competencies for advanced training in oral medicine.
AB  - OBJECTIVE: To explore international consensus for the validation of clinical
      competencies for advanced training in Oral Medicine. STUDY DESIGN: An electronic
      survey of clinical competencies was designed. The survey was sent to and
      completed by identified international stakeholders during a 10-week period. To be
      validated, an individual competency had to achieve 90% or greater consensus to
      keep it in its current format. RESULTS: Stakeholders from 31 countries responded.
      High consensus agreement was achieved with 93 of 101 (92%) competencies exceeding
      the benchmark for agreement. Only 8 warranted further attention and were reviewed
      by a focus group. No additional competencies were suggested. CONCLUSION: This is
      the first international validated study of clinical competencies for advanced
      training in Oral Medicine. These validated clinical competencies could provide a
      model for countries developing an advanced training curriculum for Oral Medicine
      and also inform review of existing curricula.

PMID- 25861957
TI  - World Workshop on Oral Medicine VI: clinical implications of medication-induced
      salivary gland dysfunction.
AB  - OBJECTIVE: This study aimed to systematically review the available literature on
      the clinical implications of medication-induced salivary gland dysfunction
      (MISGD). STUDY DESIGN: The systematic review was performed using PubMed, Embase,
      and Web of Science (through June 2013). Studies were assessed for degree of
      relevance and strength of evidence, based on whether clinical implications of
      MISGD were the primary study outcomes, as well as on the appropriateness of study
      design and sample size. RESULTS: For most purported xerogenic medications,
      xerostomia was the most frequent adverse effect. In the majority of the 129
      reviewed papers, it was not documented whether xerostomia was accompanied by
      decreased salivary flow. Incidence and prevalence of medication-induced
      xerostomia varied widely and was often associated with number and dose of
      medications. Xerostomia was most frequently reported to be mild-to-moderate in
      severity. Its onset occurred usually in the first weeks of treatment. There was
      selected evidence that medication-induced xerostomia occurs more frequently in
      women and older adults and that MISGD may be associated with other clinical
      implications, such as caries or oral mucosal alterations. CONCLUSIONS: The
      systematic review showed that MISGD constitutes a significant burden in many
      patients and may be associated with important negative implications for oral
      health.

PMID- 25861958
TI  - Nadir Testosterone after Long-Term Followup Predicts Prognosis in Patients with
      Prostate Cancer Treated with Combined Androgen Blockade.
AB  - PURPOSE: We examined the clinical significance of long-term serum testosterone
      monitoring to predict the prognosis of patients with prostate cancer treated with
      combined androgen blockade. MATERIALS AND METHODS: We retrospectively analyzed
      the records of 225 patients who underwent combined androgen blockade as first
      line therapy for prostate cancer. The prognostic values of testosterone and other
      clinical factors were evaluated with respect to prostate specific antigen
      progression-free and overall survival. RESULTS: Median patient age was 73.0
      years, median prostate specific antigen was 42.6 ng/ml and median followup was
      45.8 months. No variable associated with testosterone was predictive of
      progression-free survival. With regard to overall survival on univariate analysis
      nadir testosterone less than 16 ng/dl (p = 0.0190), less than 20 ng/dl (p =
      0.0020) and less than 32 ng/dl (p = 0.0146) were significant together with other
      clinical factors. In contrast, nadir testosterone less than 8 and less than 12
      ng/dl were not significant. Multivariate analysis showed that nadir testosterone
      less than 20 ng/dl was the significant prognostic factor (p = 0.0048). In
      addition, time to nadir testosterone was about 1 year (11.3 months). Patients
      were divided into rapid and slow types based on time to testosterone less than 20
      ng/dl before and after 6 months, respectively. No significant difference in
      overall survival was observed between the 2 types. The current results suggest
      that the critical factor for prognosis was not a rapid decrease but whether nadir
      testosterone achieved a level of less than 20 ng/dl. CONCLUSIONS: Nadir
      testosterone 20 ng/dl was the most significant cutoff level for overall survival
      in Japanese patients with prostate cancer treated with combined androgen
      blockade.

PMID- 25861959
TI  - Development of a mathematical model to predict different parameters during
      pharmaceutical wastewater treatment using TiO2 coated membrane.
AB  - The aim of present study is to develop a mathematical model to understand the
      photomineralization process for an antiseptic drug component, chlorhexidine
      digluconate using catalytic membrane. Overall process was executed in a photo
      reactor with immobilized TiO2 nanoparticles on the membrane surface, which gives
      the better recovery and reuse of the catalyst. To assess the overall process
      performance, a mathematical model has been developed for prediction of substrate
      concentration in the permeate stream and the theoretical build-up of the
      polarized layer in case of a membrane coated with TiO2 nanoparticles. In the
      developed mathematical model, the governing partial differential equation was
      solved with the help of initial boundary condition over the concentration
      boundary layer and Kozeny-Carmen equation. In this model the simultaneous change
      in the active surface area and the polarized layer thickness with the change in
      substrate concentration in the boundary layer was incorporated to enhance the
      accuracy of the model. The resulting non-linear partial differential equation,
      coupled with other non-linear ordinary differential equation is solved using
      Runga Kutta fourth order method. Average deviation between theoretical results
      and the experimental data generated in this study was found to remain within +/
      5% and precision level was maintained at 0.01%. 

PMID- 25861960
TI  - A reliable marker of vascular function: Does it exist?

PMID- 25861961
TI  - Clinically related or predictive factors and impacts on long-term treatment
      outcomes of involvement behaviors in patients with obsessive-compulsive disorder.
AB  - BACKGROUND: Patients with obsessive-compulsive disorder (OCD) frequently exhibit
      involvement behaviors (IBs) in which they accommodate their caregivers to their
      OCD symptoms by 1) asking them for reassurance, 2) forcing them to participate in
      their rituals, or 3) forcing them to assist in avoidance according to the
      patients' rules or demands. Such behaviors correspond to those of their
      caregivers, and are referred to as family accommodation (FA). METHODS: We
      performed multifactorial comparisons between 256 OCD patients with and without
      IBs in order to examine the clinical characteristics and long-term treatment
      outcomes of OCD patients with IBs. A multiple logistic regression analysis was
      also performed to identify the related and predictive factors of IBs. RESULTS: A
      total of 108 out of the 256 OCD patients examined (42%) were determined to
      exhibit IBs. OCD patients with IBs were differentially characterized by
      demographic and phenomenological characteristics (e.g. female predominance and
      poorer insight), more severe psychopathological features (e.g. lower GAFS, higher
      anxiety, or a depressive status), and poorer treatment outcomes. Furthermore, the
      predictive factors of IBs such as being female, having a higher compulsive score,
      and lower GAFS were identified by logistic analyses and structural equation
      modeling. CONCLUSION: The presence of IBs correlated with the severe clinical
      features, treatment refractoriness, and poorer long-term outcome of OCD. The
      severity of compulsions, being female, and lower GAFS were identified as
      predictive factors for the presence of IBs. Similar to FA, these findings appear
      to support the effectiveness of early identification and family-focused
      intervention in the treatment of OCD patients with IBs.

PMID- 25861962
TI  - 2015 SCAI/ACC/HFSA/STS Clinical Expert Consensus Statement on the Use of
      Percutaneous Mechanical Circulatory Support Devices in Cardiovascular Care:
      Endorsed by the American Heart Association, the Cardiological Society of India,
      and Sociedad Latino Americana de Cardiologia Intervencionista; Affirmation of
      Value by the Canadian Association of Interventional Cardiology-Association
      Canadienne de Cardiologie d'intervention.

PMID- 25861963
TI  - 2015 SCAI/ACC/HFSA/STS Clinical Expert Consensus Statement on the Use of
      Percutaneous Mechanical Circulatory Support Devices in Cardiovascular Care:
      Endorsed by the American Heart Assocation, the Cardiological Society of India,
      and Sociedad Latino Americana de Cardiologia Intervencion; Affirmation of Value
      by the Canadian Association of Interventional Cardiology-Association Canadienne
      de Cardiologie d'intervention.
AB  - Although historically the intra-aortic balloon pump has been the only mechanical
      circulatory support device available to clinicians, a number of new devices have
      become commercially available and have entered clinical practice. These include
      axial flow pumps, such as Impella((r)); left atrial to femoral artery bypass
      pumps, specifically the TandemHeart; and new devices for institution of
      extracorporeal membrane oxygenation. These devices differ significantly in their
      hemodynamic effects, insertion, monitoring, and clinical applicability. This
      document reviews the physiologic impact on the circulation of these devices and
      their use in specific clinical situations. These situations include patients
      undergoing high-risk percutaneous coronary intervention, those presenting with
      cardiogenic shock, and acute decompensated heart failure. Specialized uses for
      right-sided support and in pediatric populations are discussed and the clinical
      utility of mechanical circulatory support devices is reviewed, as are the
      American College of Cardiology/American Heart Association clinical practice
      guidelines.

PMID- 25861964
TI  - Cellular phenotype database: a repository for systems microscopy data.
AB  - MOTIVATION: The Cellular Phenotype Database (CPD) is a repository for data
      derived from high-throughput systems microscopy studies. The aims of this
      resource are: (i) to provide easy access to cellular phenotype and molecular
      localization data for the broader research community; (ii) to facilitate
      integration of independent phenotypic studies by means of data aggregation
      techniques, including use of an ontology and (iii) to facilitate development of
      analytical methods in this field. RESULTS: In this article we present CPD, its
      data structure and user interface, propose a minimal set of information
      describing RNA interference experiments, and suggest a generic schema for
      management and aggregation of outputs from phenotypic or molecular localization
      experiments. The database has a flexible structure for management of data from
      heterogeneous sources of systems microscopy experimental outputs generated by a
      variety of protocols and technologies and can be queried by gene, reagent, gene
      attribute, study keywords, phenotype or ontology terms. AVAILABILITY AND
      IMPLEMENTATION: CPD is developed as part of the Systems Microscopy Network of
      Excellence and is accessible at http://www.ebi.ac.uk/fg/sym. CONTACT:
      jes@ebi.ac.uk or ugis@ebi.ac.uk SUPPLEMENTARY INFORMATION: Supplementary data are
      available at Bioinformatics online.

PMID- 25861965
TI  - Conformational sampling and structure prediction of multiple interacting loops in
      soluble and beta-barrel membrane proteins using multi-loop distance-guided chain
      growth Monte Carlo method.
AB  - MOTIVATION: Loops in proteins are often involved in biochemical functions. Their
      irregularity and flexibility make experimental structure determination and
      computational modeling challenging. Most current loop modeling methods focus on
      modeling single loops. In protein structure prediction, multiple loops often need
      to be modeled simultaneously. As interactions among loops in spatial proximity
      can be rather complex, sampling the conformations of multiple interacting loops
      is a challenging task. RESULTS: In this study, we report a new method called
      multi-loop Distance-guided Sequential chain-Growth Monte Carlo (M-DiSGro) for
      prediction of the conformations of multiple interacting loops in proteins. Our
      method achieves an average RMSD of 1.93 A for lowest energy conformations of 36
      pairs of interacting protein loops with the total length ranging from 12 to 24
      residues. We further constructed a data set containing proteins with 2, 3 and 4
      interacting loops. For the most challenging target proteins with four loops, the
      average RMSD of the lowest energy conformations is 2.35 A. Our method is also
      tested for predicting multiple loops in beta-barrel membrane proteins. For outer
      membrane protein G, the lowest energy conformation has a RMSD of 2.62 A for the
      three extracellular interacting loops with a total length of 34 residues (12, 12
      and 10 residues in each loop). AVAILABILITY AND IMPLEMENTATION: The software is
      freely available at: tanto.bioe.uic.edu/m-DiSGro. CONTACT: jinfeng@stat.fsu.edu
      or jliang@uic.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at
      Bioinformatics online.

PMID- 25861966
TI  - AVIA v2.0: annotation, visualization and impact analysis of genomic variants and
      genes.
AB  - As sequencing becomes cheaper and more widely available, there is a greater need
      to quickly and effectively analyze large-scale genomic data. While the
      functionality of AVIA v1.0, whose implementation was based on ANNOVAR, was
      comparable with other annotation web servers, AVIA v2.0 represents an enhanced
      web-based server that extends genomic annotations to cell-specific transcripts
      and protein-level functional annotations. With AVIA's improved interface, users
      can better visualize their data, perform comprehensive searches and categorize
      both coding and non-coding variants. AVAILABILITY AND IMPLEMENTATION: AVIA is
      freely available through the web at http://avia.abcc.ncifcrf.gov. CONTACT:
      Hue.Vuong@fnlcr.nih.gov SUPPLEMENTARY INFORMATION: Supplementary data are
      available at Bioinformatics online.

PMID- 25861967
TI  - GeneTIER: prioritization of candidate disease genes using tissue-specific gene
      expression profiles.
AB  - MOTIVATION: In attempts to determine the genetic causes of human disease,
      researchers are often faced with a large number of candidate genes. Linkage
      studies can point to a genomic region containing hundreds of genes, while the
      high-throughput sequencing approach will often identify a great number of non
      synonymous genetic variants. Since systematic experimental verification of each
      such candidate gene is not feasible, a method is needed to decide which genes are
      worth investigating further. Computational gene prioritization presents itself as
      a solution to this problem, systematically analyzing and sorting each gene from
      the most to least likely to be the disease-causing gene, in a fraction of the
      time it would take a researcher to perform such queries manually. RESULTS: Here,
      we present Gene TIssue Expression Ranker (GeneTIER), a new web-based application
      for candidate gene prioritization. GeneTIER replaces knowledge-based inference
      traditionally used in candidate disease gene prioritization applications with
      experimental data from tissue-specific gene expression datasets and thus largely
      overcomes the bias toward the better characterized genes/diseases that commonly
      afflict other methods. We show that our approach is capable of accurate candidate
      gene prioritization and illustrate its strengths and weaknesses using case study
      examples. AVAILABILITY AND IMPLEMENTATION: Freely available on the web at
      http://dna.leeds.ac.uk/GeneTIER/. CONTACT: umaan@leeds.ac.uk SUPPLEMENTARY
      INFORMATION: Supplementary data are available at Bioinformatics online.

PMID- 25861968
TI  - MetaSV: an accurate and integrative structural-variant caller for next generation
      sequencing.
AB  - Structural variations (SVs) are large genomic rearrangements that vary
      significantly in size, making them challenging to detect with the relatively
      short reads from next-generation sequencing (NGS). Different SV detection methods
      have been developed; however, each is limited to specific kinds of SVs with
      varying accuracy and resolution. Previous works have attempted to combine
      different methods, but they still suffer from poor accuracy particularly for
      insertions. We propose MetaSV, an integrated SV caller which leverages multiple
      orthogonal SV signals for high accuracy and resolution. MetaSV proceeds by
      merging SVs from multiple tools for all types of SVs. It also analyzes soft
      clipped reads from alignment to detect insertions accurately since existing tools
      underestimate insertion SVs. Local assembly in combination with dynamic
      programming is used to improve breakpoint resolution. Paired-end and coverage
      information is used to predict SV genotypes. Using simulation and experimental
      data, we demonstrate the effectiveness of MetaSV across various SV types and
      sizes. AVAILABILITY AND IMPLEMENTATION: Code in Python is at
      http://bioinform.github.io/metasv/. CONTACT: rd@bina.com SUPPLEMENTARY
      INFORMATION: Supplementary data are available at Bioinformatics online.

PMID- 25861969
TI  - Applying stability selection to consistently estimate sparse principal components
      in high-dimensional molecular data.
AB  - MOTIVATION: Principal component analysis (PCA) is a basic tool often used in
      bioinformatics for visualization and dimension reduction. However, it is known
      that PCA may not consistently estimate the true direction of maximal variability
      in high-dimensional, low sample size settings, which are typical for molecular
      data. Assuming that the underlying signal is sparse, i.e. that only a fraction of
      features contribute to a principal component (PC), this estimation consistency
      can be retained. Most existing sparse PCA methods use L1-penalization, i.e. the
      lasso, to perform feature selection. But, the lasso is known to lack variable
      selection consistency in high dimensions and therefore a subsequent
      interpretation of selected features can give misleading results. RESULTS: We
      present S4VDPCA, a sparse PCA method that incorporates a subsampling approach,
      namely stability selection. S4VDPCA can consistently select the truly relevant
      variables contributing to a sparse PC while also consistently estimate the
      direction of maximal variability. The performance of the S4VDPCA is assessed in a
      simulation study and compared to other PCA approaches, as well as to a
      hypothetical oracle PCA that 'knows' the truly relevant features in advance and
      thus finds optimal, unbiased sparse PCs. S4VDPCA is computationally efficient and
      performs best in simulations regarding parameter estimation consistency and
      feature selection consistency. Furthermore, S4VDPCA is applied to a publicly
      available gene expression data set of medulloblastoma brain tumors. Features
      contributing to the first two estimated sparse PCs represent genes significantly
      over-represented in pathways typically deregulated between molecular subgroups of
      medulloblastoma. AVAILABILITY AND IMPLEMENTATION: Software is available at
      https://github.com/mwsill/s4vdpca. CONTACT: m.sill@dkfz.de SUPPLEMENTARY
      INFORMATION: Supplementary data are available at Bioinformatics online.

PMID- 25861970
TI  - Adaxial cell migration in the zebrafish embryo is an active cell autonomous
      property that requires the Prdm1a transcription factor.
AB  - Adaxial cells, the progenitors of slow-twitch muscle fibres in zebrafish, exhibit
      a stereotypic migratory behaviour during somitogenesis. Although this process is
      known to be disrupted in various mutants, its precise nature has remained
      unclear. Here, using in vivo imaging and chimera analysis, we show that adaxial
      cell migration is a cell autonomous process, during which cells become polarised
      and extend filopodia at their leading edge. Loss of function of the Prdm1a
      transcription factor disrupts the polarisation and migration of adaxial cells,
      reflecting a role that is independent of its repression of sox6 expression.
      Expression of the M- and N-cadherins, previously implicated in driving adaxial
      cell migration, is largely unaffected by loss of Prdm1a function, suggesting that
      differential cadherin expression is not sufficient for adaxial cell migration. 

PMID- 25861971
TI  - A stepwise approach for peroral endoscopic myotomy for treating achalasia: from
      animal models to patients.
AB  - OBJECTIVES: Peroral endoscopic myotomy (POEM) was initially developed for the
      treatment of achalasia. This study aimed to investigate the feasibility and
      safety of a stepwise approach for POEM in the management of achalasia. METHODS: A
      total of five ex-vivo porcine esophagus-stomach training models were created and
      POEM was performed. Then, 25 patients with achalasia were treated similarly. The
      Eckardt score, barium esophagrams, and high-resolution manometry were used to
      evaluate its efficacy. RESULTS: POEM procedures were completed in five stomach
      esophagus models, with perforations in the initial three and success in the last
      two. A total of 25 achalasia patients (13 males, 12 females) with achalasia
      successfully underwent POEM. The mean operation time was 72.0 min (range, 45-180
      min). There were two complications--one case each of severe bleeding and
      pneumothorax--that were both treated successfully. During the follow-up period,
      the median Eckardt score decreased dramatically from 8 to 1 (p = 0.000). The
      lower basal esophageal sphincter pressure decreased markedly (41.3 +/- 12.6 vs.
      11.3 +/- 4.3 mmHg, p = 0.000), as well as the 4-s integrated relaxation pressure
      (37.1 +/- 12.6 vs. 7.1 +/- 2.4 mmHg, p = 0.000). Additionally, the maximum
      esophagus width was significantly reduced (mean reduced width: 1.6 +/- 1.1 cm, p
      = 0.000). CONCLUSIONS: The ex-vivo porcine esophagus-stomach can be used as a
      simple and cheap training model that mimics the POEM procedure. POEM is a safe
      and effective therapy for achalasia patients.

PMID- 25861972
TI  - Absence of population asymmetry in the American Quarter Horse (Equus ferus
      caballus) performing skilled left and right manoeuvres in reining competition.
AB  - Use of the right hand by humans for speech-related hand gestures, writing and
      throwing exemplifies motoric asymmetry. There are reports of asymmetry in many
      other animal species, including reports of left preference in emotional
      responsivity, spontaneous behaviour and the trained performance of the horse,
      Equus ferus caballus. The present study used the novel approach of using judges'
      scores to examine asymmetry in an equestrian event. The study analysed the scores
      of five judges evaluating the reining performance of 482, three-year-old American
      Quarter Horses competing in a major competition. Reining requires that the horses
      perform the manoeuvres of spin, circle and stop directed to either the left or
      right and symmetrical performance is featured in the judging criteria. The scores
      were sensitive to performance level, sex and manoeuvre, but there was no evidence
      of a population asymmetry in the left vs. right direction of the manoeuvres. The
      results are discussed in relation to need of using a large number of subjects in
      measuring asymmetry, the expression of individual vs. population asymmetry as a
      function of morphological and behavioural measures, and the influence of
      behavioural training on asymmetry. 

PMID- 25861973
TI  - Manoeuvring between anxiety and control: patients' experience of learning to live
      with diabetes: a lifeworld phenomenological study.
AB  - Research shows that people with diabetes want their lives to proceed as normally
      as possible, but some patients experience difficulty in reaching their desired
      goals with treatment. The learning process is a complex phenomenon interwoven
      into every facet of life. Patients and healthcare providers often have different
      perspectives in care which gives different expectations on what the patients need
      to learn and cope with. The aim of this study, therefore, is to describe the
      experience of learning to live with diabetes. Interviews were conducted with 12
      patients afflicted with type 1 or type 2 diabetes. The interviews were then
      analysed with reference to the reflective lifeworld research approach. The
      analysis shows that when the afflicted realize that their bodies undergo changes
      and that blood sugar levels are not always balanced as earlier in life, they can
      adjust to their new conditions early. The afflicted must take responsibility for
      balancing their blood sugar levels and incorporating the illness into their
      lives. Achieving such goals necessitates knowledge. The search for knowledge and
      sensitivity to changes are constant requirements for people with diabetes.
      Learning is driven by the tension caused by the need for and dependence on safe
      blood sugar control, the fear of losing such control, and the fear of future
      complications. The most important responsibilities for these patients are
      aspiring to understand their bodies as lived bodies, ensuring safety and
      security, and acquiring the knowledge essential to making conscious choices. 

PMID- 25861974
TI  - Comparison of the prognosis of bisphosphonate-related osteonecrosis of the jaw
      caused by oral and intravenous bisphosphonates.
AB  - Bisphosphonates (BPs) have been used in medical practice for the treatment of
      osteoporosis, bone metastasis, and multiple myeloma. Although many studies have
      been published, the treatment and prognosis of bisphosphonate-related
      osteonecrosis of the jaw (BRONJ) remain unclear. This study included 59 patients
      with BRONJ: 29 had taken oral BPs and 30 had taken intravenous (IV) BPs. All
      received conservative treatments. When separated sequestra were seen, a
      sequestrectomy was performed. Segmental mandibular resection was performed when
      pathological fractures were diagnosed. The outcomes of treatments were compared
      between groups. For patients treated with oral rinses or mandibular resection,
      the number in whom clinical healing was observed did not differ between the oral
      BP and IV BP groups. With regard to sequestrectomy, 94% of patients in the oral
      BP group showed improvement with this treatment compared to 50% in the IV BP
      group. The number of patients in whom clinical healing of BRONJ was achieved was
      statistically better in the oral BP group than in the IV BP group after 6 months
      of treatment (P<0.001). The results showed that >90% of patients treated with
      oral BPs could be cured. However, 50% of patients treated with IV BPs did not
      show an improvement. Additional research is needed to further increase the
      therapeutic efficacy for the resolution of BRONJ. 

PMID- 25861975
TI  - HLA-B27.
AB  - Possession of the human leukocyte antigen (HLA) class I molecule B27 is strongly
      associated with ankylosing spondylitis (AS), but the pathogenic role of HLA-B27
      is unknown. Two broad theories most likely explain the role of HLA-B27 in AS
      pathogenesis. The first is based on the natural immunological function of HLA-B27
      of presenting antigenic peptides to cytotoxic T cells. Thus, HLA-B27-restricted
      immune responses to self-antigens, or arthritogenic peptides, might drive
      immunopathology. B27 can also "behave badly," misfolding during assembly and
      leading to endoplasmic reticulum stress and autophagy responses. beta2m-free B27
      heavy chain structures including homodimers (B272) can also be expressed at the
      cell surface following endosomal recycling of cell surface heterotrimers. Cell
      surface free heavy chains and B272 bind to innate immune receptors on T, NK, and
      myeloid cells with proinflammatory effects. This review describes the natural
      function of HLA-B27, its disease associations, and the current theories as to its
      pathogenic role. 

PMID- 25861977
TI  - The immunobiology of interleukin-27.
AB  - Interleukin-27 (IL-27) is a cytokine with strikingly diverse influences on the
      immune response. Although it was initially linked with the development of Th1
      responses, it is now recognized as a potent antagonist of different classes of
      inflammation through its ability to directly modify CD4(+) and CD8(+) T cell
      effector functions, to induce IL-10, and to promote specialized T regulatory cell
      responses. Although this aspect of IL-27 biology has provided insights into how
      the immune system prevents hyperactivity in the setting of infectious and
      autoimmune inflammation, in vaccination and cancer models the stimulatory effects
      of IL-27 on CD8(+) T cell function appear prominent. Additionally, associations
      between IL-27 and antibody-mediated disease have led to an interest in defining
      the impact of IL-27 on innate immunity and humoral responses in different disease
      states. The maturation of this literature has been accompanied by attempts to
      translate these findings from experimental models into human diseases and by
      efforts to define where IL-27 might represent a viable therapeutic target. 

PMID- 25861978
TI  - Early T cell activation: integrating biochemical, structural, and biophysical
      cues.
AB  - T cells carry out the formidable task of identifying small numbers of foreign
      antigenic peptides rapidly and specifically against a very noisy environmental
      background of endogenous self-peptides. Early steps in T cell activation have
      thus fascinated biologists and are among the best-studied models of cell
      stimulation. This remarkable process, critical in adaptive immune responses,
      approaches and even seems to exceed the limitations set by the physical laws
      ruling molecular behavior. Despite the enormous amount of information concerning
      the nature of molecules involved in the T cell antigen receptor (TCR) signal
      transduction network, and the description of the nanoscale organization and real
      time analysis of T cell responses, the general principles of information
      gathering and processing remain incompletely understood. Here we review currently
      accepted key data on TCR function, discuss the limitations of current research
      strategies, and suggest a novel model of TCR triggering and a few promising ways
      of going further into the integration of available data. 

PMID- 25861979
TI  - Macrophages: development and tissue specialization.
AB  - Macrophages are myeloid immune cells that are strategically positioned throughout
      the body tissues, where they ingest and degrade dead cells, debris, and foreign
      material and orchestrate inflammatory processes. Here we review two major recent
      paradigm shifts in our understanding of tissue macrophage biology. The first is
      the realization that most tissue-resident macrophages are established prenatally
      and maintained through adulthood by longevity and self-renewal. Their generation
      and maintenance are thus independent from ongoing hematopoiesis, although the
      cells can be complemented by adult monocyte-derived macrophages. Second, aside
      from being immune sentinels, tissue macrophages form integral components of their
      host tissue. This entails their specialization in response to local environmental
      cues to contribute to the development and specific function of their tissue of
      residence. Factors that govern tissue macrophage specialization are emerging.
      Moreover, tissue specialization is reflected in discrete gene expression profiles
      of macrophages, as well as epigenetic signatures reporting actual and potential
      enhancer usage. 

PMID- 25861980
TI  - Stromal cells in chronic inflammation and tertiary lymphoid organ formation.
AB  - Inflammation is an unstable state. It either resolves or persists. Why
      inflammation persists and the factors that define tissue tropism remain obscure.
      Increasing evidence suggests that tissue-resident stromal cells not only provide
      positional memory but also actively regulate the differential accumulation of
      inflammatory cells within inflamed tissues. Furthermore, at many sites of chronic
      inflammation, structures that mimic secondary lymphoid tissues are observed,
      suggesting that chronic inflammation and lymphoid tissue formation share common
      activation programs. Similarly, blood and lymphatic endothelial cells contribute
      to tissue homeostasis and disease persistence in chronic inflammation. This
      review highlights our increasing understanding of the role of stromal cells in
      inflammation and summarizes the novel immunological role that stromal cells exert
      in the persistence of inflammatory diseases. 

PMID- 25861981
TI  - Enzyme immunoassay for the detection of porcine gelatine in edible bird's nests.
AB  - Porcine gelatine is a common adulterant found in edible bird's nests (EBNs) used
      to increase the net weight prior to sale. This study aimed to develop indirect
      enzyme-linked immunosorbent assays (ELISAs) for porcine gelatine adulteration
      using anti-peptide polyclonal antibodies. Three indirect ELISAs were developed
      (PAB1, 2 and 3), which had limits of detection (LODs) of 0.12, 0.10 and 0.11 ug
      g(-1), respectively. When applied to standard solutions of porcine gelatine, the
      inter- and intra-assays showed coefficients of variation (CVs) less than 20% and
      were able to detect at least 0.5 ng ug(-1) (0.05%) porcine gelatine in spiked
      samples. The proposed ELISA offers attractions for quality control in the EBN
      industry. 

PMID- 25861982
TI  - Safety and efficacy of teneligliptin in Japanese patients with type 2 diabetes
      mellitus: a pooled analysis of two Phase III clinical studies.
AB  - OBJECTIVE: To assess the safety and efficacy of long-term administration of
      teneligliptin alone and in combination with oral antidiabetic drugs in Japanese
      type 2 diabetes mellitus (T2DM) patients with insufficient glycemic control.
      METHODS: This post-hoc pooled analysis used data from two Phase III clinical
      studies involving 702 Japanese patients. We evaluated teneligliptin as
      monotherapy and combined with a sulfonylurea, glinide, biguanide, or alpha
      glucosidase inhibitor. Safety measures included adverse events (AEs), adverse
      reactions and hypoglycemia. The main efficacy measure was the change in glycated
      hemoglobin (HbA1c) from baseline. RESULTS: Incidences of AEs and adverse
      reactions were similar among the teneligliptin monotherapy group and all
      combination therapy groups except the combination with sulfonylurea. Hypoglycemia
      was more frequent in the sulfonylurea combination therapy group than in other
      groups. Teneligliptin administered once daily as monotherapy or combination
      therapy resulted in a decrease in HbA1c, which was maintained for 52 weeks.
      Bodyweight showed no change or a slight increase at the end of 52 weeks in all
      groups. CONCLUSIONS: This pooled analysis provides evidence for the safety and
      efficacy of long-term use of teneligliptin as monotherapy or combination therapy
      in Japanese T2DM patients.

PMID- 25861976
TI  - Ion channels in innate and adaptive immunity.
AB  - Ion channels and transporters mediate the transport of charged ions across
      hydrophobic lipid membranes. In immune cells, divalent cations such as calcium,
      magnesium, and zinc have important roles as second messengers to regulate
      intracellular signaling pathways. By contrast, monovalent cations such as sodium
      and potassium mainly regulate the membrane potential, which indirectly controls
      the influx of calcium and immune cell signaling. Studies investigating human
      patients with mutations in ion channels and transporters, analysis of gene
      targeted mice, or pharmacological experiments with ion channel inhibitors have
      revealed important roles of ionic signals in lymphocyte development and in innate
      and adaptive immune responses. We here review the mechanisms underlying the
      function of ion channels and transporters in lymphocytes and innate immune cells
      and discuss their roles in lymphocyte development, adaptive and innate immune
      responses, and autoimmunity, as well as recent efforts to develop pharmacological
      inhibitors of ion channels for immunomodulatory therapy. 

PMID- 25861984
TI  - The Expanding Relevance of Routinely Collected Outcome Data for Mental Health
      Care Decision Making.
AB  - Evidence shows that routine outcome monitoring (ROM) and feedback using
      standardized measurement tools enhances the outcomes of individual patients. When
      outcome data from a large number of patients and clinicians are collected,
      patterns can be tracked and comparisons can be made at multiple levels.
      Variability in skills and outcomes among clinicians and service settings has been
      documented, and the relevance of ROM for decision making is rapidly expanding
      alongside the transforming health care landscape. In this article, we highlight
      several developing core implications of ROM for mental health care, and frame
      points of future work and discussion.

PMID- 25861983
TI  - Safety and efficacy of sustained release of basic fibroblast growth factor using
      gelatin hydrogel in patients with critical limb ischemia.
AB  - As a form of therapeutic angiogenesis, we sought to investigate the safety and
      efficacy of a sustained-release system of basic fibroblast growth factor (bFGF)
      using biodegradable gelatin hydrogel in patients with critical limb ischemia
      (CLI). We conducted a phase I-IIa study that analyzed 10 CLI patients following a
      200-MUg intramuscular injection of bFGF-incorporated gelatin hydrogel
      microspheres into the ischemic limb. Primary endpoints were safety and
      transcutaneous oxygen pressure (TcO2) at 4 and 24 weeks after treatment. During
      the follow-up, there was no death or serious procedure-related adverse event.
      After 24 weeks, TcO2 (28.4 +/- 8.4 vs. 46.2 +/- 13.0 mmHg for pretreatment vs
      after 24 weeks, p < 0.01) showed significant improvement. Regarding secondary
      endpoints, the distance walked in 6 min (255 +/- 105 vs. 318 +/- 127 m, p =
      0.02), the Rutherford classification (4.4 +/- 0.5 vs. 3.1 +/- 1.4, p = 0.02), the
      rest pain scale (1.7 +/- 1.0 vs. 1.2 +/- 1.3, p = 0.03), and the cyanotic scale
      (2.0 +/- 1.1 vs. 0.9 +/- 0.9, p < 0.01) also showed improvement. The blood levels
      of bFGF were within the normal range in all patients. A subanalysis of patients
      with arteriosclerosis obliterans (n = 7) or thromboangiitis obliterans (Buerger's
      disease) (n = 3) revealed that TcO2 had significantly improved in both subgroups.
      TcO2 did not differ between patients with or without chronic kidney disease. The
      sustained release of bFGF from biodegradable gelatin hydrogel may offer a safe
      and effective form of angiogenesis for patients with CLI. 

PMID- 25861985
TI  - Human Urinary Composition Controls Antibacterial Activity of Siderocalin.
AB  - During Escherichia coli urinary tract infections, cells in the human urinary
      tract release the antimicrobial protein siderocalin (SCN; also known as lipocalin
      2, neutrophil gelatinase-associated lipocalin/NGAL, or 24p3). SCN can interfere
      with E. coli iron acquisition by sequestering ferric iron complexes with
      enterobactin, the conserved E. coli siderophore. Here, we find that human urinary
      constituents can reverse this relationship, instead making enterobactin critical
      for overcoming SCN-mediated growth restriction. Urinary control of SCN activity
      exhibits wide ranging individual differences. We used these differences to
      identify elevated urinary pH and aryl metabolites as key biochemical host factors
      controlling urinary SCN activity. These aryl metabolites are well known products
      of intestinal microbial metabolism. Together, these results identify an innate
      antibacterial immune interaction that is critically dependent upon
      individualistic chemical features of human urine. 

PMID- 25861986
TI  - Two Isoforms of the RNA Binding Protein, Coding Region Determinant-binding
      Protein (CRD-BP/IGF2BP1), Are Expressed in Breast Epithelium and Support
      Clonogenic Growth of Breast Tumor Cells.
AB  - CRD-BP/IGF2BP1 has been characterized as an "oncofetal" RNA binding protein
      typically highly expressed in embryonic tissues, suppressed in normal adult
      tissues, but induced in many tumor types. In this study, we show that adult
      breast tissues express ubiquitous but low levels of CRD-BP protein and mRNA.
      Although CRD-BP mRNA expression is induced in breast tumor cells, levels remain
      ~1000-fold lower than in embryonic tissues. Despite low expression levels, CRD-BP
      is required for clonogenic growth of breast cancer cells. We reveal that because
      the most common protein isoform in normal adult breast and breast tumors has an N
      terminal deletion (lacking two RNA recognition motif (RRM) domains) and is
      therefore missing antibody epitopes, CRD-BP expression has been under-reported by
      previous studies. We show that a CRD-BP mutant mouse strain retains expression of
      the shorter transcript (DeltaN-CRD-BP), which originates in intron 2, suggesting
      that the impact of complete ablation of this gene in mice is not yet known.
      Either the full-length CRD-BP or the N-terminally truncated version can rescue
      the clonogenicity of CRD-BP knockdown breast cancer cells, suggesting that
      clonogenic function is served by either CRD-BP isoform. In summary, although CRD
      BP expression levels are low in breast cancer cells, this protein is necessary
      for clonogenic activity. 

PMID- 25861987
TI  - Convergence of Parkin, PINK1, and alpha-Synuclein on Stress-induced Mitochondrial
      Morphological Remodeling.
AB  - Mutations in PARKIN (PARK2), an ubiquitin ligase, cause early onset Parkinson
      disease. Parkin was shown to bind, ubiquitinate, and target depolarized
      mitochondria for destruction by autophagy. This process, mitophagy, is considered
      crucial for maintaining mitochondrial integrity and suppressing Parkinsonism.
      Here, we report that under moderate mitochondrial stress, parkin does not
      translocate to mitochondria to induce mitophagy; rather, it stimulates
      mitochondrial connectivity. Mitochondrial stress-induced fusion requires PINK1
      (PARK6), mitofusins, and parkin ubiquitin ligase activity. Upon exposure to
      mitochondrial toxins, parkin binds alpha-synuclein (PARK1), and in conjunction
      with the ubiquitin-conjugating enzyme Ubc13, stimulates K63-linked
      ubiquitination. Importantly, alpha-synuclein inactivation phenocopies parkin
      overexpression and suppresses stress-induced mitochondria fission, whereas Ubc13
      inactivation abrogates parkin-dependent mitochondrial fusion. The convergence of
      parkin, PINK1, and alpha-synuclein on mitochondrial dynamics uncovers a common
      function of these PARK genes in the mitochondrial stress response and provides a
      potential physiological basis for the prevalence of alpha-synuclein pathology in
      Parkinson disease. 

PMID- 25861988
TI  - Isolation and Characterization of a Hybrid Respiratory Supercomplex Consisting of
      Mycobacterium tuberculosis Cytochrome bcc and Mycobacterium smegmatis Cytochrome
      aa3.
AB  - Recently, energy production pathways have been shown to be viable antitubercular
      drug targets to combat multidrug-resistant tuberculosis and eliminate pathogen in
      the dormant state. One family of drugs currently under development, the
      imidazo[1,2-a]pyridine derivatives, is believed to target the pathogen's homolog
      of the mitochondrial bc1 complex. This complex, denoted cytochrome bcc, is highly
      divergent from mitochondrial Complex III both in subunit structure and inhibitor
      sensitivity, making it a good target for drug development. There is no soluble
      cytochrome c in mycobacteria to transport electrons from the bcc complex to
      cytochrome oxidase. Instead, the bcc complex exists in a "supercomplex" with a
      cytochrome aa3-type cytochrome oxidase, presumably allowing direct electron
      transfer. We describe here purification and initial characterization of the
      mycobacterial cytochrome bcc-aa3 supercomplex using a strain of M. smegmatis that
      has been engineered to express the M. tuberculosis cytochrome bcc. The resulting
      hybrid supercomplex is stable during extraction and purification in the presence
      of dodecyl maltoside detergent. It is hoped that this purification procedure will
      potentiate functional studies of the complex as well as crystallographic studies
      of drug binding and provide structural insight into a third class of the bc
      complex superfamily. 

PMID- 25861989
TI  - TRAF Family Member-associated NF-kappaB Activator (TANK) Inhibits Genotoxic
      Nuclear Factor kappaB Activation by Facilitating Deubiquitinase USP10-dependent
      Deubiquitination of TRAF6 Ligase.
AB  - DNA damage-induced NF-kappaB activation plays a critical role in regulating
      cellular response to genotoxic stress. However, the molecular mechanisms
      controlling the magnitude and duration of this genotoxic NF-kappaB signaling
      cascade are poorly understood. We recently demonstrated that genotoxic NF-kappaB
      activation is regulated by reversible ubiquitination of several essential
      mediators involved in this signaling pathway. Here we show that TRAF family
      member-associated NF-kappaB activator (TANK) negatively regulates NF-kappaB
      activation by DNA damage via inhibiting ubiquitination of TRAF6. Despite the lack
      of a deubiquitination enzyme domain, TANK has been shown to negatively regulate
      the ubiquitination of TRAF proteins. We found TANK formed a complex with MCPIP1
      (also known as ZC3H12A) and a deubiquitinase, USP10, which was essential for the
      USP10-dependent deubiquitination of TRAF6 and the resolution of genotoxic NF
      kappaB activation upon DNA damage. Clustered regularly interspaced short
      palindromic repeats (CRISPR)/Cas9-mediated deletion of TANK in human cells
      significantly enhanced NF-kappaB activation by genotoxic treatment, resulting in
      enhanced cell survival and increased inflammatory cytokine production.
      Furthermore, we found that the TANK-MCPIP1-USP10 complex also decreased TRAF6
      ubiquitination in cells treated with IL-1beta or LPS. In accordance, depletion of
      USP10 enhanced NF-kappaB activation induced by IL-1beta or LPS. Collectively, our
      data demonstrate that TANK serves as an important negative regulator of NF-kappaB
      signaling cascades induced by genotoxic stress and IL-1R/Toll-like receptor
      stimulation in a manner dependent on MCPIP1/USP10-mediated TRAF6
      deubiquitination. 

PMID- 25861991
TI  - The conserved modular elements of the acyl carrier proteins of lipid synthesis
      are only partially interchangeable.
AB  - Prior work showed that expression of acyl carrier proteins (ACPs) of a diverse
      set of bacteria replaced the function of Escherichia coli ACP in lipid
      biosynthesis. However, the AcpAs of Lactococcus lactis and Enterococcus faecalis
      were inactive. Both failed to support growth of an E. coli acpP mutant strain.
      This defect seemed likely because of the helix II sequences of the two AcpAs,
      which differed markedly from those of the proteins that supported growth. To test
      this premise, chimeric ACPs were constructed in which L. lactis helix II replaced
      helix II of E. coli AcpP and vice versa. Expression of the AcpP protein L. lactis
      AcpA helix II allowed weak growth, whereas the L. lactis AcpA-derived protein
      that contained E. coli AcpP helix II failed to support growth of the E. coli
      mutant strain. Replacement of the L. lactis AcpA helix II residues in this
      protein showed that substitution of valine for the phenylalanine residue four
      residues downstream of the phosphopanthetheine-modified serine gave robust growth
      and allowed modification by the endogenous AcpS phosphopantetheinyl transferase
      (rather than the promiscuous Sfp transferase required to modify the L. lactis
      AcpA and the chimera of L. lactis AcpA helix II in AcpP). Further chimera
      constructs showed that the lack of function of the L. lactis AcpA-derived protein
      containing E. coli AcpP helix II was due to incompatibility of L. lactis AcpA
      helix I with the downstream elements of AcpP. Therefore, the origins of ACP
      incompatibility can reside in either helix I or in helix II. 

PMID- 25861990
TI  - The Human Mitochondrial DNA Depletion Syndrome Gene MPV17 Encodes a Non-selective
      Channel That Modulates Membrane Potential.
AB  - The human MPV17-related mitochondrial DNA depletion syndrome is an inherited
      autosomal recessive disease caused by mutations in the inner mitochondrial
      membrane protein MPV17. Although more than 30 MPV17 gene mutations were shown to
      be associated with mitochondrial DNA depletion syndrome, the function of MPV17 is
      still unknown. Mice deficient in Mpv17 show signs of premature aging. In the
      present study, we used electrophysiological measurements with recombinant MPV17
      to reveal that this protein forms a non-selective channel with a pore diameter of
      1.8 nm and located the channel's selectivity filter. The channel was weakly
      cation-selective and showed several subconductance states. Voltage-dependent
      gating of the channel was regulated by redox conditions and pH and was affected
      also in mutants mimicking a phosphorylated state. Likewise, the mitochondrial
      membrane potential (Deltapsim) and the cellular production of reactive oxygen
      species were higher in embryonic fibroblasts from Mpv17(-/-) mice. However,
      despite the elevated Deltapsim, the Mpv17-deficient mitochondria showed signs of
      accelerated fission. Together, these observations uncover the role of MPV17 as a
      Deltapsim-modulating channel that apparently contributes to mitochondrial
      homeostasis under different conditions. 

PMID- 25861992
TI  - Methylation of Gata3 protein at Arg-261 regulates transactivation of the Il5 gene
      in T helper 2 cells.
AB  - Gata3 acts as a master regulator for T helper 2 (Th2) cell differentiation by
      inducing chromatin remodeling of the Th2 cytokine loci, accelerating Th2 cell
      proliferation, and repressing Th1 cell differentiation. Gata3 also directly
      transactivates the interleukin-5 (Il5) gene via additional mechanisms that have
      not been fully elucidated. We herein identified a mechanism whereby the
      methylation of Gata3 at Arg-261 regulates the transcriptional activation of the
      Il5 gene in Th2 cells. Although the methylation-mimicking Gata3 mutant retained
      the ability to induce IL-4 and repress IFNgamma production, the IL-5 production
      was selectively impaired. We also demonstrated that heat shock protein (Hsp) 60
      strongly associates with the methylation-mimicking Gata3 mutant and negatively
      regulates elongation of the Il5 transcript by RNA polymerase II. Thus, arginine
      methylation appears to play a pivotal role in the organization of Gata3 complexes
      and the target gene specificity of Gata3. 

PMID- 25861993
TI  - An N-terminal Amphipathic Helix Binds Phosphoinositides and Enhances Kalirin
      Sec14 Domain-mediated Membrane Interactions.
AB  - Previous studies revealed an essential role for the lipid-binding Sec14 domain of
      kalirin (KalSec14), but its mechanism of action is not well understood. Because
      alternative promoter usage appends unique N-terminal peptides to the KalSec14
      domain, we used biophysical, biochemical, and cell biological approaches to
      examine the two major products, bKalSec14 and cKalSec14. Promoter B encodes a
      charged, unstructured peptide, whereas promoter C encodes an amphipathic helix
      (Kal-C-helix). Both bKalSec14 and cKalSec14 interacted with lipids in PIP strip
      and liposome flotation assays, with significantly greater binding by cKalSec14 in
      both assays. Disruption of the hydrophobic face of the Kal-C-helix in
      cKalSec14KKED eliminated its increased liposome binding. Although cKalSec14
      showed significantly reduced binding to liposomes lacking phosphatidylinositol
      phosphates or cholesterol, liposome binding by bKalSec14 and cKalSec14KKED was
      not affected. When expressed in AtT-20 cells, bKalSec14-GFP was diffusely
      localized, whereas cKalSec14-GFP localized to the trans-Golgi network and
      secretory granules. The amphipathic C-helix was sufficient for this localization.
      When AtT-20 cells were treated with a cell-permeant derivative of the Kal-C-helix
      (Kal-C-helix-Arg9), we observed increased secretion of a product stored in mature
      secretory granules, with no effect on basal secretion; a cell-permeant control
      peptide (Kal-C-helixKKED-Arg9) did not have this effect. Through its ability to
      control expression of a novel, phosphoinositide-binding amphipathic helix, Kalrn
      promoter usage is expected to affect function. 

PMID- 25861994
TI  - Comparison of pain management after laparoscopic distal gastrectomy with and
      without epidural analgesia.
AB  - PURPOSE: The optimal analgesia following laparoscopic distal gastrectomy (LDG)
      has not been determined; moreover, it has been unclear whether epidural
      anesthesia has benefits for laparoscopic surgery. In this study, we evaluated the
      effectiveness of epidural analgesia after LDG. METHODS: This retrospective study
      included 84 patients who underwent LDG for gastric cancer. Patients received
      either combined thoracic epidural and general anesthesia (Epidural group, n = 34)
      or general anesthesia alone (No epidural group, n = 50). We recorded data on the
      patients, surgery, postoperative outcomes and anesthesia-related complications.
      RESULTS: In the Epidural group, the first day of flatus was significantly earlier
      (2.21 vs. 2.44 days, p = 0.045) and the number of additional doses of analgesics
      was significantly lower (2.85 vs. 4.86 doses, p = 0.007) than in the No epidural
      group. Postoperative urinary retention occurred at a significantly higher rate in
      the Epidural group (n = 7; 20.6 %) than in the No epidural group (p < 0.001).
      CONCLUSION: Epidural anesthesia may reduce the need for additional analgesics
      after LDG, but increases the risk of urinary retention.

PMID- 25861996
TI  - Effect of a single injection of tranexamic acid on blood loss after primary
      hybrid TKA.
AB  - BACKGROUND: Control of perioperative blood loss is important in total knee
      arthroplasty (TKA), especially cementless or hybrid TKA. There is increasing
      interest in the use of tranexamic acid (TXA) for this purpose, however, studies
      to date have mainly evaluated the effects of various TXA administration regimens
      on patients who have undergone cemented TKA. We sought to determine (1) whether
      administration of TXA reduces blood loss after hybrid TKA, and (2) whether an
      autologous blood reinfusion system is necessary in TKA patients who are treated
      with TXA. METHODS: Ninety-five patients (100 knees) who underwent hybrid primary
      TKA (cemented tibia, uncemented femur) were included in this study. The initial
      50 knees were treated without TXA and the following 50 were treated with TXA.
      Intravenous TXA (1000 mg) was administered shortly before deflation of the
      tourniquet. All continuous variables were expressed as median values. RESULTS:
      Total volumes of blood lost at postoperative 1 day were 590 mL and 150 mL and
      autotransfusion of collected blood was performed in 88% and 16% of patients in
      the without and with TXA groups, respectively. A median volume of 400 mL of
      collected blood was returned to the patients in the without TXA group, and 0 mL
      to the patients in the with TXA group. The calculated volumes of blood lost were
      761 mL and 683 mL (p=0.2250), respectively. CONCLUSIONS: One intravenous
      injection of 1000 mg TXA may help to control postoperative blood loss and reduce
      the need for postoperative autologous blood reinfusion after hybrid TKA. LEVEL OF
      EVIDENCE: Level II.

PMID- 25861997
TI  - The clinical course of an overgrowth syndrome, from diagnosis in infancy through
      adulthood: the case of Beckwith-Wiedemann syndrome.
AB  - Beckwith-Wiedemann syndrome (BWS) is the most common genetic overgrowth syndrome,
      and it is frequently clinically recognizable because of characteristic features.
      These features include macrosomia, hemihypertrophy, macroglossia, facial nevus
      flammeus, earlobe creases and pits, omphalocele, and organomegaly. The most
      common molecular cause is hypomethylation of the maternal imprinting control
      region 2 (ICR2) in 11p15. Other molecular causes include hypermethylation of the
      maternal ICR1 in 11p15, mutations in CDKN1C, mosaic uniparental disomy 11p15, and
      chromosomal abnormalities involving 11p15. Some of these abnormalities are
      testable, and DNA methylation tests of 11p15 confirm about 60% of cases with BWS.
      The main management issues in pediatrics are hypoglycemia at birth, macroglossia,
      and surveillance for embryonal tumors, especially Wilms and hepatoblastoma. 

PMID- 25861998
TI  - Foreword: overgrowth syndromes.

PMID- 25861995
TI  - Rett Syndrome: Reaching for Clinical Trials.
AB  - Rett syndrome (RTT) is a syndromic autism spectrum disorder caused by loss-of
      function mutations in MECP2. The methyl CpG binding protein 2 binds
      methylcytosine and 5-hydroxymethycytosine at CpG sites in promoter regions of
      target genes, controlling their transcription by recruiting co-repressors and co
      activators. Several preclinical studies in mouse models have identified rational
      molecular targets for drug therapies aimed at correcting the underlying neural
      dysfunction. These targeted therapies are increasingly translating into human
      clinical trials. In this review, we present an overview of RTT and describe the
      current state of preclinical studies in methyl CpG binding protein 2-based mouse
      models, as well as current clinical trials in individuals with RTT. 

PMID- 25861999
TI  - Generalized overgrowth syndromes with prenatal onset.
AB  - Children with generalized overgrowth syndromes are large at birth, or have
      excessive postnatal growth. Many of these syndromes are associated with an
      increase in neoplasia. Consideration of the possibility of overgrowth syndrome in
      a pediatric patient who presents with increased growth parameters, variable
      malformations and neurodevelopmental phenotype, and distinctive features, is
      important for medical management, reproductive counseling, and tumor surveillance
      for some of the disorders. This review describes the clinical features and
      surveillance recommendations for the common generalized overgrowth syndromes the
      pediatrician may encounter. It also provides a glimpse into advances of recent
      years in understanding the molecular mechanisms responsible for the disrupted
      growth regulation in these disorders. 

PMID- 25862000
TI  - Predictors of Clavien 4 Complications and Mortality After Necrosectomy: Analysis
      of the NSQIP Database.
AB  - BACKGROUND: Acute severe pancreatitis is one of the most common gastrointestinal
      reasons for admission to hospitals in the USA. Up to 20 % of these patients will
      progress to necrotizing pancreatitis requiring intervention. The aim of this
      study is to identify specific preoperative factors for the development of Clavien
      4 complications and mortality in patients undergoing pancreatic necrosectomy.
      METHODS: The American College of Surgeons National Surgical Quality Improvement
      Program (ACS-NSQIP) participant use files were reviewed from 2007 to 2012 to
      identify patients who underwent a pancreatic necrosectomy. Postoperative
      complications were stratified into Clavien 4 (ICU level complications) and
      Clavien 5 (mortality). Univariate and multivariate analyses were performed.
      RESULTS: A total of 1156 patients underwent a pancreatic necrosectomy from 2007
      to 2012. Overall, 42 % of patients experienced a Clavien 4 complication.
      Mortality rate was 9.5 %. Nonindependent functional status and ASA class were
      highly significant (p < 0.001) in univariate analysis. Frailty and emergency
      surgery status (p < 0.001), as well as increased blood urea nitrogen (BUN) and
      alkaline phosphatase and decreased albumin (p < 0.05) demonstrated independent
      significance of Clavien 4 complications and mortality in multivariate analysis.
      CONCLUSION: This study identified specific preoperative variables that place
      patients at increased risk of Clavien 4 complications and mortality after
      necrosectomy. Identification of high-risk patients can aid in selection of
      appropriate treatment strategies and allow for informed preoperative discussion
      regarding surgical risk.

PMID- 25862001
TI  - Delayed Gastric Emptying After Pancreaticoduodenectomy: Is Subtotal Stomach
      Preserving Better or Pylorus Preserving?
AB  - BACKGROUND: Delayed gastric emptying (DGE) is one of the main complications after
      pancreaticoduodenectomy (PD). Literature review and meta-analysis were used to
      evaluate whether subtotal stomach-preserving pancreaticoduodenectomy (SSPPD) may
      have less incidence than pylorus-preserving pancreaticoduodenectomy (PPPD).
      METHODS: Online search for studies comparing PPPD to SSPPD was done. Primary
      outcome was DGE. Quality of included studies was evaluated and heterogeneity was
      assessed. Relative risk (RR) and 95% confidence intervals (CI) were calculated
      from pooled data in RCTs and retrospective studies. RESULTS: Eight studies met
      our selection criteria, with a total of 663 patients undergoing
      pancreaticoduodenectomy; 309 underwent PPPD and 354 underwent SSPPD. Median age
      was 66 years. Average male/female ratio was 57 vs. 43%, respectively. There was
      lower incidence of DGE with SSPPD (RR 0.527; 95% CI 0.363-0.763; p < 0.001) and
      less nasogastric tube days with SSPPD (RR -0.544; 95% CI -876 to -0.008; p =
      0.047). Operative blood loss was more in SSPPD (RR 0.285; 95% CI 0.071-0.499; p =
      0.009). There was no statistical difference between the two groups regarding
      length of hospital stay, incidence of pancreatic fistula, abscesses, overall
      morbidity, or postoperative mortality. CONCLUSION: SSPPD was associated with less
      DGE than PPPD. Larger prospective randomized studies are needed to investigate
      the association of this result with other complications in more depth.

PMID- 25862002
TI  - [Validating the Spanish version of the Nursing Activities Score].
AB  - INTRODUCTION: Validating workload scores ensures that they are appropriate for
      the purpose for which they were developed. OBJECTIVE: To validate the Nursing
      Activities Score (NAS) Spanish version. METHODOLOGY: Observational and
      prospective study. 1,045 patients who were admitted to a medical-surgical unit
      and a serious burns unit in 2006 were included. The nurse in charge assessed
      patient workloads by Nine Equivalent of Nursing Manpower use Score and NAS. To
      assess the internal consistency of the measurements of NAS, item-test
      correlations, Cronbach's alpha and Cronbach's alpha corrected by omitting each of
      the items were calculated. The intraobserver and interobserver reliability were
      assessed with the intraclass correlation coefficient by viewing recordings and
      Kappa (interobserver reliability) was estimated. For the analysis of internal
      validity, a factorial principal components analysis was performed. Convergent
      validity was assessed using the Spearman correlation coefficient values obtained
      from the Nine Equivalent of Nursing Manpower use Score and Spanish-NAS scales.
      RESULTS: For internal consistency, 164 questionnaires were analysed and a
      Cronbach's alpha of 0.373 was calculated. The intraclass correlation coefficient
      for intraobserver reliability estimate was 0.837 (95% IC: 0.466-0.950) and 0.662
      (95% IC: 0.033-0.882) for interobserver reliability. The estimated kappa was
      0.371. For internal validity, exploratory factor analysis showed that the first
      item explained 58.9% of the variance of the questionnaire. For convergent
      validity 1006 questionnaires were included and a Spearman correlation coefficient
      of 0.746 was observed. CONCLUSIONS: The psychometric properties of Spanish-NAS
      are acceptable.

PMID- 25862003
TI  - Being underweight in middle age is associated with raised dementia risk, large
      study finds.

PMID- 25862004
TI  - PTPIP51 levels in glioblastoma cells depend on inhibition of the EGF-receptor.
AB  - Protein tyrosine phosphatase interacting protein 51 (PTPIP51) is upregulated in
      glioblastoma multiforme (GBM) and expression levels correlate with the grade of
      malignancy in gliomas. A similar correlation was reported for its interacting
      partner 14-3-3beta, which has been shown to facilitate the interaction of PTPIP51
      with cRAF (Raf1). Since the interaction of these signalling partners stimulates
      growth factor signalling downstream of the epidermal growth factor receptor
      (EGFR), a major drug target in GBM, we here investigated the impact of EGFR
      inhibition by small molecule inhibitors or monoclonal antibody on PTPIP51. The
      effect of EGFR inhibition on PTPIP51 mRNA, protein expression and its interaction
      profile in GBM was analyzed using the U87 cell line as model system. The
      transferability of the results to in vivo conditions was evaluated in cultured
      tumour cells from GBM patients. Cells were treated either to the small molecule
      tyrosine kinase inhibitor of EGFR Gefitinib or the monoclonal antibody Cetuximab
      in a time and dose dependent manner. Gefitinib treatment decreased the
      proliferation rate and induced apoptosis in U87 and primary tumour cells. The
      PTPIP51 interaction profile changed in correlation to the applied Gefitinib.
      Despite unchanged mRNA levels PTPIP51 protein was reduced. In contrast, treatment
      with Cetuximab had no effects on PTPIP51 expression. In conclusion, our results
      demonstrate the impact of EGFR inhibition by Gefitinib on PTPIP51 protein
      expression, a downstream regulator of MAPK signalling. These data will serve as a
      basis to unravel the precise role of PTPIP51-mediated signalling in GBM and its
      potential implications for Gefitinib-mediated therapy in future studies. 

PMID- 25862006
TI  - Hypofractionated radiosurgery has a better safety profile than single fraction
      radiosurgery for large resected brain metastases.
AB  - The purpose of this study is to compare the safety and efficacy of single
      fraction radiosurgery (SFR) with hypofractionated radiosurgery (HR) for the
      adjuvant treatment of large, surgically resected brain metastases. Seventy-five
      patients with 76 resection cavities >= 3 cm received 15 Gray (Gy) * 1 SFR (n =
      40) or 5-8 Gy * 3-5 HR (n = 36). Cumulative incidence of local failure (LF) and
      radiation necrosis (RN) was estimated accounting for death as a competing risk
      and compared with Gray's test. The effect of multiple covariates was evaluated
      with the Fine-Gray proportional hazards model. The most common HR dose
      fractionation schedules were 6 Gy * 5 (44%), 7-8 Gy * 3 (36%), and 6 Gy * 4 (8%).
      The median follow-up was 11 months (range 2-71). HR patients had larger median
      resection cavity volumes (24.0 vs. 13.3 cc, p < 0.001), planning target volumes
      (PTV) (37.7 vs. 20.5 cc, p < 0.001), and cavity to PTV expansion margins (2 vs.
      1.5 mm, p = 0.002) than SFR patients. Cumulative incidence of LF (95% CI) at 6
      and 12-months for HR versus SFR was 18.9% (0.07-0.34) versus 15.9% (0.06-0.29),
      and 25.6% (0.12-0.42) versus 27.2% (0.14-0.42), p = 0.80. Cumulative incidence of
      RN (95% CI) at 6 and 12 months for HR vs. SFR was 3.3% (0.00-0.15) versus 10.7%
      (0.03-0.23), and 10.3% (0.02-0.25) versus 19.2% (0.08-0.34), p = 0.28. On
      multivariable analysis, SFR was significantly associated with an increased risk
      of RN, with a HR of 3.81 (95% CI 1.04-13.93, p = 0.043). Hypofractionated
      radiosurgery may be the more favorable treatment approach for radiosurgery of
      cavities 3-4 cm in size and greater.

PMID- 25862007
TI  - Selection of suitable reference genes for expression analysis in human glioma
      using RT-qPCR.
AB  - In human glioma research, quantitative real-time reverse-transcription PCR is a
      frequently used tool. Considering the broad variation in the expression of
      candidate reference genes among tumor stages and normal brain, studies using
      quantitative RT-PCR require strict definition of adequate endogenous controls.
      This study aimed at testing a panel of nine reference genes [beta-2
      microglobulin, cytochrome c-1 (CYC1), glyceraldehyde-3-phosphate dehydrogenase
      (GAPDH), hydroxymethylbilane synthase, hypoxanthine guanine phosphoribosyl
      transferase 1, ribosomal protein L13a (RPL13A), succinate dehydrogenase, TATA-box
      binding protein and 14-3-3 protein zeta] to identify and validate the most
      suitable reference genes for expression studies in human glioma of different
      grades (World Health Organization grades II-IV). After analysis of the stability
      values calculated using geNorm, NormFinder, and BestKeeper algorithms, GAPDH,
      RPL13A, and CYC1 can be indicated as reference genes applicable for accurate
      normalization of gene expression in glioma compared with normal brain and
      anaplastic astrocytoma or glioblastoma alone within this experimental setting.
      Generally, there are no differences in expression levels and variability of
      candidate genes in glioma tissue compared to normal brain. But stability analyses
      revealed just a small number of genes suitable for normalization in each of the
      tumor subgroups and across these groups. Nevertheless, our data show the
      importance of validation of adequate reference genes prior to every study. 

PMID- 25862005
TI  - Survival prediction in high-grade gliomas using CT perfusion imaging.
AB  - Patients with high-grade gliomas usually have heterogeneous response to surgery
      and chemoirradiation. The objectives of this study were (1) to evaluate serial
      changes in tumor volume and perfusion imaging parameters and (2) to determine the
      value of these data in predicting overall survival (OS). Twenty-nine patients
      with World Health Organization grades III and IV gliomas underwent magnetic
      resonance (MR) and computed tomography (CT) perfusion examinations before
      surgery, and 1, 3, 6, 9, and 12 months after radiotherapy. Serial measurements of
      tumor volumes and perfusion parameters were evaluated by receiver operating
      characteristic analysis, Cox proportional hazards regression, and Kaplan-Meier
      survival analysis to determine their values in predicting OS. Higher trends in
      blood flow (BF), blood volume (BV), and permeability-surface area product in the
      contrast-enhancing lesions (CEL) and the non-enhancing lesions (NEL) were found
      in patients with OS < 18 months compared to those with OS >= 18 months, and these
      values were significant at selected time points (P < 0.05). Only CT perfusion
      parameters yielded sensitivities and specificities of >= 70% in predicting 18 and
      24 months OS. Pre-surgery BF in the NEL and BV in the CEL and NEL 3 months after
      radiotherapy had sensitivities and specificities >80% in predicting 24 months OS
      in patients with grade IV gliomas. Our study indicated that CT perfusion
      parameters were predictive of survival and could be useful in assessing early
      response and in selecting adjuvant treatment to prolong survival if verified in a
      larger cohort of patients.

PMID- 25862008
TI  - Contrast enhancement pattern predicts poor survival for patients with non-WNT/SHH
      medulloblastoma tumours.
AB  - Recent studies revealed the biological heterogeneity of medulloblastoma, with the
      existence of at least four groups which are associated with several clinical and
      morphological features. We investigated for further correlations between
      molecular types, location of tumours, their contrast enhancement pattern and
      survival of patients. Altogether 76 tumours were analyzed and molecular subtypes
      were identified by immunohistochemistry using representative antibodies,
      detection of chromosome 6 monosomy and CTNNB1 mutation. The site of the tumour
      was assessed on diagnosis using Magnetic Resonance images and intra-operative
      surgical reports. In addition, the gadolinium enhancement pattern was also
      investigated in pre-treatment tumours. Cerebellar hemispheric location was
      associated with SHH tumours (p < 0.001), as opposed to midline location being
      typical for WNT and non-WNT/SHH tumours. Remarkably, for patients with non
      WNT/SHH tumours, the extensive gadolinium enhancement pattern (present in >75% of
      tumour volume) predicted worse OS and EFS than for those with none/weak or
      heterogeneous enhancement (>10-75% of tumour volume), (both p < 0.001). Our
      analysis indicates that distribution of the medulloblastoma tumours location is
      related to the biological characteristics of tumour. Importantly, the enhancement
      pattern of the tumour may be a clinically useful prognostic marker for patients
      with non-WNT/SHH medulloblastomas.

PMID- 25862009
TI  - Anaplastic ganglioglioma: a report of three cases and review of the literature.
AB  - Gangliogliomas are rare tumors of the central nervous system that are thought to
      arise from a glioneuronal precursor and consist of both neuronal and glial
      elements. Grade III, or anaplastic ganglioglioma (AGG), most commonly affects
      children and young adults, generally arises in a supratentorial location, is
      highly epileptogenic, and often results in diffuse local and distant failure
      within the craniospinal axis. Pathologically, these tumors are graded by the
      degree of malignancy in their glial portion and radiologic diagnosis is difficult
      due to the wide variation in its degree of solid and cystic components, contrast
      uptake, and calcification patterns. This report presents three cases of AGG, with
      initial treatment including subtotal resection followed by conformal
      radiotherapy. In the case where the AGG developed in the setting of an existent
      low-grade astrocytoma, the patient received no chemotherapy. Both of the other de
      novo cases were managed with adjuvant chemoradiotherapy with temozolomide.
      Recurrence occurred at 6, 16, and 20 months following therapy. Two of the three
      patients experienced symptomatic decline at recurrence, but experienced Karnofsky
      performance status (KPS) improvement after salvage therapy, including the
      reduction of cranial neuropathy and balance. All patients had a significant
      reduction in presenting symptoms following salvage therapy. Patients died at 23,
      20, and 22 months following initial surgical management, respectively. A review
      of anaplastic and malignant gangliogliomas is presented in the context of these
      three cases.

PMID- 25862011
TI  - Safety, cost, and clinical considerations for the use of premixed parenteral
      nutrition.
AB  - Premixed parenteral nutrition (PN) can be used for PN therapy in place of
      traditional compounded or customized PN. Premixed PN may have a number of
      advantages over compounded PN such as decreased costs, decreased compounding
      time, reduced chance for error, and reduced incidence of bloodstream infections.
      However, premixed PN may not be appropriate for all patients and may have other
      additional costs associated with its use. This article discusses the data
      available with regard to the use of premixed PN, focusing on the potential
      advantages and disadvantages of using premixed PN, and also discusses the
      implementation of premixed PN in a large tertiary cancer center.

PMID- 25862010
TI  - Nationwide registry-based ecological analysis of Q fever incidence and pregnancy
      outcome during an outbreak in the Netherlands.
AB  - OBJECTIVE: Whether areas affected by Q fever during a large outbreak (2008-2010)
      had higher rates of adverse pregnancy outcomes than areas not affected by Q
      fever. DESIGN: Nationwide registry-based ecological study. SETTING: Pregnant
      women in areas affected and not affected by Q fever in the Netherlands, 2003-2004
      and 2008-2010. PARTICIPANTS: Index group (N=58,737): pregnant women in 307 areas
      with more than two Q fever notifications. Reference group (N=310,635): pregnant
      women in 921 areas without Q fever notifications. As a baseline, pregnant women
      in index and reference areas in the years 2003-2004 were also included in the
      reference group to estimate the effect of Q fever in 2008-2010, and not the
      already existing differences before the outbreak. MAIN OUTCOME MEASURES: Preterm
      delivery, small for gestational age, perinatal mortality. RESULTS: In 2008-2010,
      there was no association between residing in a Q fever-affected area and both
      preterm delivery (adjusted OR 1.01 (95% CI 0.94 to 1.08)), and perinatal
      mortality (adjusted OR 0.87 (95% CI 0.72 to 1.05)). In contrast, we found a weak
      significant association between residing in a Q fever-affected area in 2008-2010
      and small for gestational age (adjusted OR 1.06 (95% CI 1.01 to 1.12)), with a
      population-attributable fraction of 0.70% (95% CI 0.07% to 1.34%). We observed no
      dose-response relation for this outcome with increasing Q fever notifications,
      and we did not find a stronger association for women who were in their first
      trimester of pregnancy during the months of high human Q fever incidence.
      CONCLUSIONS: This study found a weak association between residing in a Q fever
      affected area and the pregnancy outcome small for gestational age. Early
      detection of infection would require mass screening of pregnant women; this does
      not seem to be justified considering these results, and the uncertainties about
      its efficacy and the adverse effects of antibiotic treatment.

PMID- 25862013
TI  - Nintedanib in the treatment of idiopathic pulmonary fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal lung
      disease that occurs in older adults. The clinical course of IPF is variable and
      hard to predict in an individual patient. Nintedanib is a tyrosine kinase
      inhibitor that has recently been approved in the US and European Union for the
      treatment of IPF. Preclinical studies have shown that nintedanib interferes with
      processes active in fibrosis such as fibroblast proliferation, migration and
      differentiation and the secretion of extracellular matrix. The safety and
      efficacy of nintedanib have been investigated in the phase II TOMORROW trial and
      in two replicate 52-week randomized, placebo-controlled phase III trials known as
      the INPULSIS trials. These trials demonstrated that nintedanib slowed disease
      progression by reducing the annual rate of decline in forced vital capacity, with
      a manageable side-effect profile. In this review, we summarize key data
      supporting nintedanib as a treatment for patients with IPF and address key
      questions regarding the use of nintedanib in the clinical setting. 

PMID- 25862012
TI  - Dolutegravir Has No Effect on the Pharmacokinetics of Oral Contraceptives With
      Norgestimate and Ethinyl Estradiol.
AB  - BACKGROUND: Dolutegravir (DTG; Tivicay; ViiV Healthcare, Research Triangle Park,
      NC) is an HIV-1-unboosted integrase inhibitor with no cytochrome P450 or uridine
      5'diphosphate-glucuronosyltransferase inhibition or induction. As DTG is
      administered to HIV-1-infected women receiving oral contraceptives, assessing the
      potential for drug interactions was warranted. OBJECTIVE: To determine the impact
      of DTG on the pharmacokinetics (PK) and pharmacodynamics (PD) of a common oral
      contraceptive, norgestimate/ethinyl estradiol (NGM/EE; Ortho-Cyclen; Ortho-McNeil
      Janssen Pharmaceuticals, Inc, Raritan, NJ). METHODS: This randomized, 2-period,
      double-blind, placebo-controlled study was conducted within 1 menstrual cycle at
      1 clinical center in the United States; 16 women were enrolled. Participants
      received NGM 0.25 mg/EE 0.035 mg throughout the study. During days 1 to 10, they
      were randomized to receive twice-daily DTG 50 mg or matching placebo with food
      and switched to the other treatment during days 12 to 21. RESULTS: Ratios of area
      under the concentration-time curve from time 0 until end of the dosage interval
      (AUC0-tau), maximum plasma concentration, and concentration at the end of the
      dosage interval of norelgestromin with DTG treatment to the same PK parameters
      with placebo treatment were 0.975, 0.890, and 0.932, respectively; for EE, ratios
      were 1.03, 0.99, and 1.02, respectively. No significant differences in
      luteinizing hormone, follicle-stimulating hormone, and progesterone were detected
      on days 1, 10, 11, 21, and 22. DTG steady-state AUC0-tau was similar to
      historical data. No severe or grade 3/4 adverse events occurred. CONCLUSIONS: DTG
      had no effect on NGM/EE PK or PD. NGM/EE can be administered with DTG without
      dose adjustment.

PMID- 25862014
TI  - High production of fumaric acid from xylose by newly selected strain Rhizopus
      arrhizus RH 7-13-9#.
AB  - Fumaric acid, as an important material for polymerization, is highly expected to
      be produced by fermentation of lignocellulosic biomass which is composed of
      cellulose, hemicellulose and lignin. Xylose as the main component of
      hemicellulose cannot be efficiently utilized by most of the common fermentation.
      In this study, a new strain Rhizopus arrhizus RH 7-13-9# was selected from the R.
      arrhizus RH 7-13 through a novel convenient and efficient selection method.
      Efficient production of fumaric acid (45.31 g/L) from xylose was achieved by the
      new strain, and the volumetric productivity was still 0.472 g/L h. Moreover, the
      conversion of xylose reached 73% which is close to the theoretic yield (77%). The
      production of fumaric acid was increased approximate by 172%, compared with the
      initial strain counterpart. These results indicated that xylose, as the main
      component of hemicellulose, has a promising application for the production of
      fumaric acid on an industrial-scale.

PMID- 25862015
TI  - Synthesis of macroporous silica biomass nanocomposite based on XG/MgSiO3 for the
      removal of toxic ions.
AB  - Biomass is known as a low-cost adsorbents and there is a need for the development
      of synthesis method further increase its efficient applications. In this work, a
      macroporous nanocomposite biomass was synthesized by natural polymer (Xanthan
      gum) and silicate. The resulting nanocomposite was characterized with XRD, SEM,
      TEM, BET and FTIR. The analysis confirmed that the functions silicate groups were
      successfully introduced and the nanocomposite not only showed a special
      macroporous structure but also showed a better cation exchange capacity which
      helps to retain cation ions. What's more, in order to investigate the adsorption
      capacity of the biomass, adsorption experiments were considered. The experiment
      results revealed that nanocomposite showed a high-efficiency adsorption capacity
      to remove toxic ions such as arsenic, chromium, mercury and cadmium. 

PMID- 25862016
TI  - Difference in the expression of IL-9 and IL-17 correlates with different
      histological pattern of vascular wall injury in giant cell arteritis.
AB  - OBJECTIVE: GCA is a large- and medium-vessel arteritis characterized by a range
      of histological patterns of vascular wall injury. The aim of this study was to
      immunologically characterize the various histological patterns of GCA. METHODS:
      Thirty-five consecutive patients with biopsy-proven GCA and 15 normal controls
      were studied. IL-8, IL-9, IL-9R, IL-17, IL-4, TGF-beta and thymic stromal
      lymphopoietin expression was evaluated by RT-PCR and immunohistochemistry on
      artery biopsy specimens. Confocal microscopy was used to characterize the
      phenotypes of IL-9-producing and IL-9R-expressing cells. Five additional patients
      who had received prednisone when the temporal artery biopsy was performed were
      also enrolled to evaluate the effect of glucocorticoids on IL-9 and IL-17
      expression. RESULTS: IL-17 overexpression was observed mainly in arteries with
      transmural inflammation and vasa vasorum vasculitis. IL-9 overexpression and Th9
      polarization predominated in arteries with transmural inflammation and small
      vessel vasculitis. The tissue expression of both IL-9 and IL-17 was correlated
      with the intensity of the systemic inflammatory response. IL-4, TGF-beta and
      thymic stromal lymphopoietin, which are involved in the differentiation of Th9
      cells, were overexpressed in arteries with transmural inflammation and small
      vessel vasculitis. IL-9R was also overexpressed in GCA arteries with transmural
      inflammation and was accompanied by increased expression of IL-8. CONCLUSION:
      Herein we provide the first evidence that distinct populations of potentially
      autoreactive T cells, expressing different cytokines (Th17 vs Th9), characterize
      patients with particular histological subsets of GCA and may thus contribute to
      the heterogeneity of tissue lesions observed in these patients.

PMID- 25862017
TI  - Downregulation of viral RNA translation by hepatitis C virus non-structural
      protein NS5A requires the poly(U/UC) sequence in the 3' UTR.
AB  - Hepatitis C virus (HCV) non-structural protein 5A (NS5A) is essential for viral
      replication; however, its effect on HCV RNA translation remains controversial
      partially due to the use of reporters lacking the 3' UTR, where NS5A binds to the
      poly(U/UC) sequence. We investigated the role of NS5A in HCV translation using a
      monocistronic RNA containing a Renilla luciferase gene flanked by the HCV UTRs.
      We found that NS5A downregulated viral RNA translation in a dose-dependent
      manner. This downregulation required both the 5' and 3' UTRs of HCV because
      substitution of either sequence with the 5' and 3' UTRs of enterovirus 71 or a
      cap structure at the 5' end eliminated the effects of NS5A on translation.
      Translation of the HCV genomic RNA was also downregulated by NS5A. The inhibition
      of HCV translation by NS5A required the poly(U/UC) sequence in the 3' UTR as NS5A
      did not affect translation when it was deleted. In addition, we showed that,
      whilst the amphipathic alpha-helix of NS5A has no effect on viral translation,
      the three domains of NS5A can inhibit translation independently, also dependent
      on the presence of the poly(U/UC) sequence in the 3' UTR. These results suggested
      that NS5A downregulated HCV RNA translation through a mechanism involving the
      poly(U/UC) sequence in the 3' UTR. 

PMID- 25862018
TI  - "I was that close": Investigating Players' Reactions to Losses, Wins, and Near
      Misses on Scratch Cards.
AB  - While scratch cards are a popular, accessible, and inexpensive form of gambling,
      very little is known about how they affect and influence the player. This study
      sought to understand the physiological and subjective experience of scratch card
      play, with special emphasis on the effect of near-miss outcomes (i.e. uncovering
      two out of three "grand prize" symbols needed to win said prize), which are
      remarkably prevalent in scratch card games. Thirty-eight undergraduate students
      from the University of Waterloo each played two custom scratch card games and
      experienced three types of outcomes (losses, wins and near-misses) while their
      skin conductance levels (SCLs) and post-reinforcement pauses were recorded. Each
      participant also rated each outcome in terms of its subjective level of arousal,
      valence, and frustration. Our results indicate that players interpreted near
      misses as negatively valenced, highly arousing, frustrating losses, and were
      faster to move onto the next game following this type of outcome than following
      winning outcomes. Additionally, near-miss outcomes were associated with the
      largest amount of change in SCLs as the outcome was revealed. This work has
      implications for the problem gambling literature as it provides evidence of the
      frustration hypothesis of near-misses in scratch cards, and is the first study to
      examine the physiological and psychological experiences of scratch card players. 

PMID- 25862019
TI  - Gambling Patterns and Problems of Gamblers on Licensed and Unlicensed Sites in
      France.
AB  - In 2010 France enacted a law to regulate supply and consumption of online
      gambling. Its primary aim was to protect citizens from gambling-related harm.
      This study aims to assess differences in gambling patterns and related harm
      between online gamblers who use licensed versus unlicensed sites. Participants (N
      = 3860) completed a self-administered online survey on gambling practices.
      Pairwise logistic regressions examined the association between the legal statuses
      of gambling sites people patronized and demographic variables and gambling types.
      Multivariate logistic regression models explored associations between gambling
      patterns and related problems according to the legal status of sites people have
      gambled on. Overall, 53.7 % of online gamblers report gambling exclusively on
      licensed sites. Those who bet on regulated activities on unlicensed sites, versus
      licensed sites, are more likely to be female, younger, less educated, inactive in
      the labor market and are more likely to perceive their financial situation to be
      difficult. Gambling on unlicensed sites is associated with more intense gambling
      patterns and more gambling-related problems compared to licensed sites. Findings
      demonstrate that gambling activities carried out on state licensed sites are
      associated with less overall harm to gamblers. Implications of these findings on
      future policy are discussed and prospective research directions are outlined. 

PMID- 25862020
TI  - Identification of Novel Inflammatory Cytokines and Contribution of Keratinocyte
      Derived Chemokine to Inflammation in Response to Vibrio vulnificus Infection in
      Mice.
AB  - Currently, only tumor necrosis factor alpha (TNF-alpha) and interleukin family
      cytokines have been found to be elicited in Vibrio vulnificus (V. vulnificus)
      infected animal models and humans. However, multiple other cytokines are also
      involved in the immune and inflammatory responses to foreign microorganism
      infection. Antibody array technology, unlike traditional enzyme-linked
      immunosorbent assay (ELISA), is able to detect multiple cytokines at one time.
      Therefore, in this study, we examined the proinflammatory cytokine profile in the
      serum and liver homogenate samples of bacterial-infected mice using antibody
      array technology. We identified nine novel cytokines in response to V. vulnificus
      infection in mice. We found that keratinocyte-derived chemokine (KC) was the most
      elevated cytokine and demonstrated that KC played a very important role in the V.
      vulnificus infection-elicited inflammatory response in mice, as evidenced by the
      fact that the blocking of KC by anti-KC antibody reduced hepatic injury in vivo
      and that KC induced by V. vulnificus infection in AML-12 cells chemoattracted
      neutrophils. Our findings implicate that KC may serve as a novel diagnostic
      biomarker and a possible therapeutic target for V. vulnificus infection. 

PMID- 25862021
TI  - An infant with nephrolithiasis and renal failure: Questions.

PMID- 25862022
TI  - An infant with nephrolithiasis and renal failure: Answers.

PMID- 25862023
TI  - Validation of automated Greulich-Pyle bone age determination in children with
      chronic renal failure?
AB  - Growth failure is a common problem in children with chronic kidney disease (CKD).
      The causes are multifactorial and are associated with increased mortality and
      morbidity. Standard deviations of bone age versus chronological age in children
      with CKD have not been developed to date. Accurate and early treatment of bone
      age is an important component of determining the utility of GH therapy.
      Improvements in bone age assessments are being evaluated to optimize the
      understanding of growth delay in CKD. 

PMID- 25862024
TI  - Topical corticosteroid-induced skin atrophy: a comprehensive review.
AB  - Skin atrophy is an adverse effect of topical corticosteroids (TCs) which, as an
      established non-life-threatening effect, has been poorly reported by trials
      involving these drugs. Atopic dermatitis and psoriasis are example of disorders
      that require repeated therapies with TCs; however, assessing the atrophogenic
      activity of TCs is still an issue. This study aims to review clinical data on
      skin atrophy induced by TCs. Searches of the PubMed, EMBASE, and Cochrane
      (Central) databases from 1965 to May 2013 were undertaken using the keywords
      'corticosteroid', 'skin', and 'atrophy'. Skin and epidermal thickness values were
      retrieved from trials on healthy skin, and studies including skin atrophy as a
      safety endpoint in trials testing the efficacy of TCs were analyzed. Overall, 60
      articles were retrieved. Whole skin and epidermal thickness were relevant
      parameters to measure early skin atrophy on healthy skin before it becomes
      clinically obvious. Epidermis thickness also seems to be more sensitive than
      whole skin thickness in detecting early atrophy; however, measuring skin atrophy
      still requires standardization. Further clinical trials on the atrophic effects
      of each TC are required to better evaluate their respective atrophic risks and
      their risk/benefit ratios. However, measuring epidermal or whole skin thickness
      will not be relevant in acute phases of inflammatory skin disorders treated with
      TCs because of the thickening induced by inflammation. In addition, skin atrophy
      seems to be induced by chronic TC use rather than by acute treatments. Long-term
      safety studies may be more relevant to evaluate atrophic activity. 

PMID- 25862025
TI  - Parathyroid Reimplantation in Forearm Subcutaneous Tissue During Thyroidectomy: A
      Simple and Effective Way to Avoid Hypoparathyroidism.
AB  - INTRODUCTION: Parathyroid autotransplantation plays an important role in
      preventing hypoparathyroidism following thyroidectomy. The preferred
      reimplantation site is still the sternocleidomastoid muscle, but this approach
      does not permit to check graft vitality postoperatively. The authors report the
      first prospective evaluation of normal parathyroid gland reimplantation in
      forearm subcutaneous tissue (using the same technique proposed during
      parathyroidectomy for hyperplasia) in case of devascularized or inadvertently
      removed glands during thyroid surgery. MATERIALS AND METHODS: From January 2013
      to August 2014, we performed 348 consecutive thyroidectomies for various disease,
      both benign and malignant. In 25 cases, due to inadvertent parathyroid removal or
      evidence of insufficient blood supply, we removed and fragmented the gland into
      0.5-1 mm slices (one for frozen section) and reimplanted it into two subcutaneous
      pockets on the non-dominant forearm. After surgery we checked grafted gland
      function by evaluation of serum parathormone gradient between reimplanted versus
      non-reimplanted arm (considering significant a ratio of 1.5 or more), at 1 week,
      1 and 3 months after surgery. RESULTS: We observed recovery of reimplanted graft
      function in 48, 88 and 96% of patients respectively at 1 week, 1 and 3 months
      after surgery. All patients showed normal parathormone levels in peripheral blood
      (non-reimplanted arm). In one case we observed post-operative wound hematoma on
      graft-site. This patient showed no graft functionality in post-operative period
      (even at 3 months follow-up). CONCLUSIONS: Parathyroid gland reimplantation in
      forearm subcutaneous tissue during thyroid surgery is a safe, easy and effective
      procedure; furthermore, it allows a good control of graft functionality and would
      allow an easy grafted gland removal if needed.

PMID- 25862026
TI  - Identification and management of the ilio-inguinal and ilio-hypogastric nerves in
      open inguinal hernia repair: benefits of self-gripping mesh.
AB  - PURPOSE: A large randomized, multicenter European study recently reported a
      reduction in early pain after open inguinal surgery when self-gripping mesh was
      used compared with sutured Lichtenstein repair. This secondary exploratory study
      is focused on the influence of nerve identification and handling on post
      operative pain. METHODS: Post-operative VAS pain data and Surgical Pain Scores
      (SPS) from 507 patients included in this study were analyzed according to whether
      inguinal nerves were preserved or resected during surgery to investigate whether
      identification and peri-operative nerve handling impact post-operative pain.
      RESULTS: Preservation of the ilio-hypogastric nerve during Lichtenstein mesh
      repair with suture fixation was associated with significantly more post-operative
      pain compared with resection at each follow-up (p <= 0.003). This difference was
      not significant with self-gripping mesh repair. The decrease from baseline in
      post-operative VAS and SPS scores were significantly greater after self-gripping
      mesh repair compared to Lichtenstein repair at 1 year, but only when the ilio
      hypogastric nerve was preserved (VAS scores, p = 0.009; SPS scores, p = 0.015).
      No such difference was observed with the ilio-inguinal nerve. When self-gripping
      mesh was used, preservation of the ilio-hypogastric nerve was associated with
      significantly greater decreases in post-operative pain (change in VAS score from
      baseline) compared with Lichtenstein repair at each follow-up (p <= 0.018).
      CONCLUSIONS: The ilio-hypogastric nerve is in danger of being traumatized during
      Lichtenstein mesh repair with suture fixation. The use of self-gripping mesh was
      shown to reduce the level of post-operative pain when the ilio-hypogastric nerve
      was preserved. Resection of the ilio-hypogastric nerve during Lichtenstein repair
      eliminates this difference.

PMID- 25862027
TI  - Abdominal wall hernia and pregnancy: a systematic review.
AB  - PURPOSE: There is no consensus as to the treatment strategy for abdominal wall
      hernias in fertile women. This study was undertaken to review the current
      literature on treatment of abdominal wall hernias in fertile women before or
      during pregnancy. METHODS: A literature search was undertaken in PubMed and
      Embase in combination with a cross-reference search of eligible papers. RESULTS:
      We included 31 papers of which 23 were case reports. In fertile women undergoing
      sutured or mesh repair, pain was described in a few patients during the last
      trimester of a subsequent pregnancy. Emergency surgery of incarcerated hernias in
      pregnant women, as well as combined hernia repair and cesarean section appears as
      safe procedures. No major complications were reported following hernia repair
      before or during pregnancy. The combined procedure of elective cesarean section
      and abdominal wall hernia repair was reported in 102 patients without major
      complications. CONCLUSIONS: The literature on abdominal wall hernia and pregnancy
      is sparse. Abdominal wall hernia repair with suture or mesh may cause pain in the
      last trimester of a subsequent pregnancy. Hernia repair in conjunction with
      cesarean section appear as the optimal treatment of a pregnant patient with a
      symptomatic abdominal wall hernia.

PMID- 25862028
TI  - Bacterial adhesion to biological versus polymer prosthetic materials used in
      abdominal wall defect repair: do these meshes show any differences in vitro?
AB  - PURPOSE: Although clinical data suggest the similar performance of collagen-based
      biological prosthetic materials to some polymer materials, the use of a biomesh
      for abdominal hernia repair in a setting of infection is controversial. This in
      vitro study compares the adhesion of two Staphylococcus strains to polymer and
      biological meshes. METHODS: Sterile fragments of Optilene((r)) (Op), SurgiproTM
      (Surg), Preclude((r)) (Precl), TIGR((r)) (TIGR), Bio-A((r)) (BioA), PermacolTM
      (Perm), Surgisis((r)) (SIS), and Tutomesh((r)) (Tuto) were inoculated with 10(6)
      CFU of S. aureus (Sa) or S. epidermidis (Se) (n = 18 per strain per mesh). The
      first five meshes are polymer materials while Perm, SIS and Tuto are biomeshes.
      After 24/48 h of incubation, bacterial adhesion was examined by sonication,
      scanning electron microscopy (SEM) and light microscopy. RESULTS: Sa and Se
      showed a high affinity for the absorbable meshes (TIGR, BioA, Perm, SIS, Tuto) (p
      < 0.001). Precl yielded the lowest bacterial loads (p < 0.001). Surg, Precl and
      BioA underwent no substantial change over time, while Op (p < 0.001) and TIGR (p
      < 0.05) showed decreasing bacterial loads during incubation. The Sa-contaminated
      biomeshes behaved similarly while biomeshes inoculated with Se returned higher
      bacterial yields at 48 h, especially SIS (p < 0.001). SEM and light microscopy
      observations revealed planktonic bacteria and biofilms on the polymer surface and
      bacterial niches in biomesh pores. CONCLUSIONS: Within 48 h of contamination, the
      absorbable polymer and biological meshes exhibited high bacterial loads. Given
      their lower affinity for both bacterial strains, the conventional non-absorbable
      polymer materials could be better candidates for use in contaminated surgical
      fields.

PMID- 25862029
TI  - Redescription of Aphalloides coelomicola Dollfus, Chabaud & Golvan, 1957
      (Digenea, Opisthorchioidea) based on specimens from Knipowitschia caucasica
      (Berg) (Actinopterygii, Gobionellidae) from a Black Sea lagoon, with comments on
      the systematic position of the genus.
AB  - The genus Aphalloides Dollfus, Chabaud & Golvan, 1957 consists of two species
      parasitic in the body cavity of sand gobies. Its systematic position in the
      superfamily Opisthorchioidea Looss, 1899 is unresolved and it has been placed by
      various authors in three families, i.e. Cryptogonimidae Ward, 1917, Heterophyidae
      Leiper, 1909 and Opisthorchiidae Looss, 1899. Its type-species, Aphalloides
      coelomicola Dollfus, Chabaud & Golvan, 1957, is here reported from the Caucasian
      dwarf goby Knipowitschia caucasica (Berg) in the lagoon Atanasovsko Lake, Black
      Sea coast of Bulgaria (new geographical record). The species is redescribed based
      on light and scanning electron microscopy demonstrating some characters typical
      for the Cryptogonimidae but also characters distinguishing it from the other
      genera of the family such as the lack of tegumental spines and the presence of a
      short excretory vesicle, which does not extend into the forebody. Phylogenetic
      analysis of the D2-D3 expansion segments of the 28S rRNA gene suggests
      phylogenetic relationships of Aphalloides coelomicola with the cryptogonimid
      Centrovarium lobotes (MacCallum, 1895). These data support the affiliation of the
      genus Aphalloides to the family Cryptogonimidae. The peculiar morphology of the
      species in the genus is explained by their unusual life-cycles characterised by
      progenetic development; sand gobies being simultaneously second intermediate and
      definitive hosts. 

PMID- 25862030
TI  - An annotated list of the species of Gangesia Woodland, 1924 (Cestoda:
      Proteocephalidea), parasites of catfishes in Asia, with new synonyms and a key to
      their identification.
AB  - An annotated list of tapeworms of the genus Gangesia Woodland, 1924 (Cestoda:
      Proteocephalidea), parasites of siluriform fishes in Asia, is provided. Based on
      the morphological examination of museum specimens and newly collected material
      from China, Japan and Russia, as well as the results of a previous revision of
      the Indomalayan species, only eight of more than 50 nominal taxa are considered
      to be valid. These are: from India and neighbouring countries, Gangesia
      bengalensis (Southwell, 1913) (type-species), G. agraensis Verma, 1928, both from
      Wallago attu (Bloch & Schneider) (Siluridae), G. macrones Woodland, 1924 from
      Sperata seenghala (Sykes) (Bagridae) and G. vachai (Gupta & Parmar, 1988) from
      different catfishes (type-host Eutropiichthys vacha (Hamilton); Schilbeidae),
      and, from the Palaearctic, G. margolisi Shimazu, 1994, a parasite of Silurus
      biwaensis (Tomoda) (Siluridae) in Japan, G. oligonchis Roitman & Freze, 1964 from
      Tachysurus fulvidraco (Richardson) (Bagridae) in Russia, and G. parasiluri
      Yamaguti, 1934 and G. polyonchis Roitman & Freze, 1964, both from Silurus asotus
      L. (Siluridae) in Japan and Russia, respectively. The poorly known G. oligonchis
      is redescribed. Seven new synonyms are proposed: G. chauhani Mathur & Srivastav,
      2000, G. wallaguae Pradhan, Kulkarni, Kale & Wakle, 2010 and G. shivajiraoi
      Dhole, Waghmare & Chavan, 2012 are synonymised with G. agraensis; G. striatusii
      Bhure & Nanaware, 2012 and Silurotaenia govindii Sawarkar, 2013 with G. macrones;
      G. spasskajae Demshin, 1987 with G. polyonchis; and Silurotaenia spinula Chen,
      1984 with Postgangesia orientalis Akhmerov, 1969. Gangesia pseudobagrae Chen,
      1962 is considered to be a species inquirenda, whereas G. chauhani Mathur, 1992
      and G. dineshei Jaysingpure, 2002 are recognised as unavailable names. An amended
      generic diagnosis of Gangesia and a key to the identification of its recognised
      species are also provided. 

PMID- 25862031
TI  - Dichelyne (Cucullanellus) romani n. sp. (Nematoda: Cucullanidae) in notacanthid
      fishes from the Northeast Atlantic and Western Mediterranean.
AB  - A new cucullanid, Dichelyne (Cucullanellus) romani n. sp. (Nematoda:
      Cucullanidae), is described from the digestive tract of two notacanthid fishes,
      Notacanthus chemnitzii Bloch and N. bonaparte Risso (Notacanthiformes:
      Notacanthidae), from the Northeast Atlantic and Western Mediterranean. The
      presence of a precloacal sucker and ten pairs of caudal papillae in males
      allocates it to the subgenus Cucullanellus Tornquist, 1931. The new species
      differs from other members of this subgenus in its larger body size, smaller
      spicule/body length ratio, the distribution of caudal papillae, and the position
      of deirids and excretory pore. Both notacanthid fishes act as definitive hosts
      with slightly larger nematode specimens detected in N. chemnitzii. A wide
      intraspecific variability was found in the distribution of caudal papillae, and
      in some specimens the position of deirids, excretory pore and length of
      intestinal caecum also varied. A complete list of all assigned species of the
      subgenus Cucullanellus is presented and discussed as there are several
      uncertainties regarding the validity and synonymy of some species. This is the
      first species of Dichelyne Jagerskiold, 1902 in a notacanthid fish and one of the
      only two records in deep-sea fish species. 

PMID- 25862032
TI  - A morphological and molecular study of two species of Raphidascaroides Yamaguti,
      1941 (Nematoda: Anisakidae), parasites of doradid catfish (Siluriformes) in South
      America, with a description of R. moraveci n. sp.
AB  - Nematodes of the genus Raphidascaroides Yamaguti, 1941 parasitising doradid
      catfishes (Siluriformes: Doradidae) in Brazil were studied based on morphological
      and molecular evaluation of newly collected material. A new species,
      Raphidascaroides moraveci n. sp., is described from the intestine of Platydoras
      armatulus (Valenciennes) from River Miranda, River Paraguay basin, Pantanal, Mato
      Grosso do Sul. The new species differs from all of the congeners in having short
      spicules (163-217 MUm in length) representing less than 1% of the total body
      length and in the posterior region of cloacal opening covered by small
      rudimentary spines. In addition, it differs from the other congeneric species in
      the number and arrangement of the caudal papillae and the structure of lips and
      tail. Raphidascaroides moraveci n. sp. is the third species described from
      freshwater fishes and the second one in the Neotropical Region. New morphological
      data on R. brasiliensis Moravec & Thatcher, 1997 from Megalodoras uranoscopus
      (Eigenmann & Eigenmann) and Platydoras costatus (Linnaeus) (both new host
      records) from River Xingu, River Amazon basin, Para, are provided including
      scanning electron micrographs of taxonomically important structures. The
      differentiation of the new species is supported by molecular data (partial
      sequences of the small and large subunits of the rRNA gene). 

PMID- 25862033
TI  - Anuran trypanosomes: phylogenetic evidence for new clades in Brazil.
AB  - Trypanosomes of anurans and fish are grouped into the Aquatic Clade which
      includes species isolated from fish, amphibians, turtles and platypus, usually
      transmitted by leeches and phlebotomine sand flies. Trypanosomes from Brazilian
      frogs are grouped within the Aquatic Clade with other anuran trypanosome species,
      where there seems to be coevolutionary patterns with vertebrate hosts and
      association to Brazilian biomes (Atlantic Forest, Pantanal and Amazonia
      Rainforest). We characterised the anuran trypanosomes from two different areas of
      the Cerrado biome and examined their phylogenetic relationships based on the SSU
      rRNA gene. A total of 112 anurans of six species was analysed and trypanosome
      prevalence evaluated through haemoculture was found to be 7% (8 positive frogs).
      However, only three isolates (2.7%) from two anuran species were recovered and
      cryopreserved. Analysis including SSU rDNA sequences from previous studies
      segregated the anuran trypanosomes into six groups, the previously reported An01
      to An04, and An05 and An06 reported herein. Clade An05 comprises the isolates
      from Leptodactylus latrans (Steffen) and Pristimantis sp. captured in the Cerrado
      biome and Trypanosoma chattoni Mathis & Leger, 1911. The inclusion of new
      isolates in the phylogenetic analyses provided evidence for a new group (An06) of
      parasites from phlebotomine hosts. Our results indicate that the diversity of
      trypanosome species is underestimated since studies conducted in Brazil and other
      regions of the world are still few. 

PMID- 25862034
TI  - Description of Myxobolus balatonicus n. sp. (Myxozoa: Myxobolidae) from the
      common carp Cyprinus carpio L. in Lake Balaton.
AB  - Myxobolus balatonicus n. sp. was detected in the gill filaments of the common
      carp Cyprinus carpio L. collected in Lake Balaton, Hungary. Its oval plasmodia
      measuring 600-800 * 300-400 um were located intravasally in the filamental
      arteries. The spores measured 11.2 +/- 0.92 * 9.5 +/- 0.41 * 7.4 +/- 0.33 um and
      had two equal polar capsules with six filamental turns. Both morphology and DNA
      sequence analysis revealed that M. balatonicus n. sp. is distinct from the ten
      species of Myxobolus Butschli, 1882 described from the European common carp and
      the 21 species described from the Asian common carp subspecies. Phylogenetic
      analysis placed M. balatonicus n. sp. in a clade of gill-infecting myxobolids. 

PMID- 25862035
TI  - The discovery of the male of Caligus ligusticus Brian, 1906 (Copepoda: Caligidae)
      parasitic on the sand steenbras Lithognathus mormyrus (L.) in the eastern
      Mediterranean.
AB  - Caligus ligusticus Brian, 1906 (Copepoda: Caligidae), a species of parasitic
      copepod originally based on females collected from off Genova, Italy, is
      redescribed based on newly collected specimens of both sexes. The new material
      was collected from the inner opercular surface of the sand steenbras Lithognathus
      mormyrus (Linnaeus) caught in eastern Mediterranean waters off the Turkish coast.
      Inadequately described female structures from earlier descriptions are re
      described and illustrated in detail and the male of C. ligusticus is described
      for the first time. Key diagnostic characters of C. ligusticus are highlighted by
      scanning electron microscopy observations. A comparative study of the newly
      collected specimens of C. ligusticus and material collected by A. Brian and
      stored in the collections of the Museum National d'Histoire Naturelle in Paris,
      is also presented. 

PMID- 25862036
TI  - Morphology, seasonality and phylogenetic relationships of Ceratomyxa husseini n.
      sp. from the gall-bladder of Cephalopholis hemistiktos (Ruppell) (Perciformes:
      Serranidae) in the Arabian Gulf off Saudi Arabia.
AB  - During a survey of myxosporean parasites of marine fishes from the Arabian Gulf
      in Saudi Arabia, spores of Ceratomyxa husseini n. sp. were found in the gall
      bladders of 50 out of 148 specimens (33.8%) of the yellowfin hind Cephalopholis
      hemistiktos (Ruppell) (Perciformes: Serranidae). The rates of infection showed a
      seasonal fluctuation, with the highest prevalence in winter and the lowest in
      autumn. The mature spores appeared arched in frontal view with rounded valve ends
      and a slightly discriminated curved suture line and measured 8-9 * 14-18 (9 * 16)
      MUm. The two polar capsules were spherical and equal in size, 4-5 (4.5) MUm in
      diameter. The polar filament showed four turns obliquely to the longitudinal axis
      of the capsules and the sporoplasm filled half of the entire spore cavity.
      Partial sequences of the small subunit rRNA gene of C. husseini n. sp. showed
      percentage of identity with other species of Ceratomyxa ranging between 79.8 and
      92.7%. The morphometric and molecular data, in association, confirmed that the
      present new species differs from all other Ceratomyxa spp. reported to date. 

PMID- 25862037
TI  - Pitching performance and longevity after revision ulnar collateral ligament
      reconstruction in Major League Baseball pitchers.
AB  - BACKGROUND: Medial ulnar collateral ligament (UCL) reconstruction is a common
      procedure performed on professional pitchers in Major League Baseball (MLB).
      Although a great deal is known about primary reconstruction, much less is known
      about revision reconstruction. PURPOSE/HYPOTHESIS: The purpose of this study was
      to evaluate statistical performance, return to play, and career longevity in MLB
      pitchers after revision UCL surgery, with the hypothesis that pitching
      performance and career longevity will decline after revision surgery. STUDY
      DESIGN: Cohort study; Level of evidence, 3. METHODS: A total of 33 MLB pitchers
      who underwent revision UCL reconstruction surgery (UCL-R group) were identified
      and compared with 33 age- and position-matched controls (CTL group). Return to
      play, total years played, and statistical performance were evaluated and compared
      with controls. RESULTS: After revision surgery, 65.5% of UCL-R pitchers returned
      to the MLB level. On average, the UCL-R pitchers played 0.8 years less in the
      majors (P<.01) than did the control pitchers. The UCL-R pitchers who returned to
      the MLB level had a similar earned run average (UCL-R: 4.88, CTL: 4.76, P=.82)
      and walks/hits per innings pitched (UCL-R: 1.58, CTL: 1.44, P=.22) compared with
      the control pitchers. There were significant declines, however, in terms of
      innings pitched (UCL-R: 36.95, CTL: 75.00, P<.01), walks per 9 innings (UCL-R:
      4.75, CTL: 3.49, P<.01), and wins (UCL-R: 1.88, CTL: 4.10, P<.01) as well as
      nonsignificant declines in wins above replacement (UCL-R: 0.25, CTL: 0.62, P=.06)
      and runs above replacement (UCL-R: 3.26, CTL: 6.91, P=.07). CONCLUSION: MLB
      pitchers who undergo UCL-R have a low rate of return to MLB play and have
      shortened careers after return. Pitchers who returned to the MLB level maintained
      performance in several statistics such as earned run average and walks/hits per
      innings pitched; however, pitchers returned with a significantly decreased
      workload.

PMID- 25862038
TI  - Posterior Instability of the Shoulder: A Systematic Review and Meta-analysis of
      Clinical Outcomes.
AB  - BACKGROUND: To date, there are no reports in the literature of a systematic
      review and meta-analysis for posterior instability of the shoulder. PURPOSE: The
      primary objective was to systematically capture, critically evaluate, and perform
      a meta-analysis of all available literature on arthroscopic clinical outcomes to
      provide insight and clinical recommendations for unilateral posterior shoulder
      instability. The secondary objective was to use the same means to assess clinical
      outcome literature for open treatment, of which a subset of highly reported
      outcome measures were used to determine superiority of arthroscopic versus open
      procedures for unilateral posterior shoulder. STUDY DESIGN: Systematic review,
      meta-analysis. METHODS: A systematic search to obtain every available, published,
      level of evidence study reporting patient data for unidirectional posterior
      shoulder instability was performed by use of the Cochrane Database of Systematic
      Reviews, PubMed/Medline database, manual searches of high impact factor journals
      and conference proceedings, and secondary references appraised for studies
      meeting inclusion criteria. RESULTS: The systematic search captured a total of
      1035 publications. After initial exclusion criteria were applied, 607 abstracts
      were assessed for eligibility. Full-text articles were obtained for 324 articles,
      and a total of 53 unique publications (27 arthroscopic studies, 26 open studies)
      reporting clinical outcomes for unidirectional posterior shoulder instability met
      inclusion criteria and were included in the systematic review and meta-analysis.
      CONCLUSION: Well-defined and uniform shoulder outcome measures to assess
      posterior shoulder instability are lacking throughout the literature. However,
      arthroscopic procedures are shown to be an effective and reliable treatment for
      unidirectional posterior glenohumeral instability with respect to outcome scores,
      patient satisfaction, and return to play. Despite similar results of outcome
      measures to the overall athletic population, throwing athletes are less likely to
      return to their preinjury levels of sport compared with contact athletes or the
      overall athletic population. Evidence also indicates that arthroscopic
      stabilization procedures using suture anchors result in fewer recurrences and
      revisions than anchorless repairs in young adults engaging in highly demanding
      physical activity. Furthermore, the literature suggests that patients treated
      arthroscopically have superior outcomes compared with patients who undergo open
      procedures with respect to stability, recurrence of instability, patient
      satisfaction, return to sport, and return to previous level of play.

PMID- 25862040
TI  - Effectiveness of treatment based on transpulmonary thermodilution in critically
      ill patients.

PMID- 25862041
TI  - Peripheral venous waveform analysis for detecting early hemorrhage: a pilot
      study.

PMID- 25862039
TI  - Early use of polymyxin B hemoperfusion in patients with septic shock due to
      peritonitis: a multicenter randomized control trial.
AB  - PURPOSE: To test whether the polymyxin B hemoperfusion (PMX HP) fiber column
      reduces mortality and organ failure in peritonitis-induced septic shock (SS) from
      abdominal infections. METHOD: Prospective, multicenter, randomized controlled
      trial in 18 French intensive care units from October 2010 to March 2013,
      enrolling 243 patients with SS within 12 h after emergency surgery for
      peritonitis related to organ perforation. The PMX HP group received conventional
      therapy plus two sessions of PMX HP. Primary outcome was mortality on day 28;
      secondary outcomes were mortality on day 90 and a reduction in the severity of
      organ failures based on Sequential Organ Failure Assessment (SOFA) scores.
      RESULTS:  PRIMARY OUTCOME: day 28 mortality in the PMX HP group (n = 119) was
      27.7 versus 19.5% in the conventional group (n = 113), p = 0.14 (OR 1.5872, 95%
      CI 0.8583-2.935). Secondary endpoints: mortality rate at day 90 was 33.6% in PMX
      HP versus 24% in conventional groups, p = 0.10 (OR 1.6128, 95% CI 0.9067-2.8685);
      reduction in SOFA score from day 0 to day 7 was -5 (-11 to 6) in PMX-HP versus -5
      (-11 to 9), p = 0.78. Comparable results were observed in the predefined
      subgroups (presence of comorbidity; adequacy of surgery, <2 sessions of
      hemoperfusion) and for SOFA reduction from day 0 to day 3. CONCLUSION: This
      multicenter randomized controlled study demonstrated a non-significant increase
      in mortality and no improvement in organ failure with PMX HP treatment compared
      to conventional treatment of peritonitis-induced SS.

PMID- 25862042
TI  - Effectiveness of treatment based on transpulmonary thermodilution in critically
      ill patients: response to comments by Sanchez et al.

PMID- 25862043
TI  - Pulsed-field gel electrophoresis for disease monitoring and control.
AB  - Pulsed-field gel electrophoresis (PFGE) is the "gold standard" for molecular
      subtyping and has significant applications in disease monitoring and control
      programs. This chapter discusses the advantages of PFGE in light of developing
      technologies such as whole-genome sequencing. 

PMID- 25862044
TI  - Harmonization of PFGE profile analysis by using bioinformatics tools: example of
      the Listeria monocytogenes European Union Reference Laboratory network.
AB  - Standardization in comparison and interpretation of profiles is an integral part
      of the analysis of gels from pulsed-field gel electrophoresis. Using Listeria
      monocytogenes as an example, this chapter outlines the analytical process using
      the software BioNumerics. 

PMID- 25862045
TI  - PFGE as a tool to track Listeria monocytogenes in food processing facilities:
      case studies.
AB  - The use of PFGE to track Listeria monocytogenes strains from the food processing
      environment to the food is explained in this chapter through two case studies.
      This illustrates the usefulness of this method to identify putative routes of
      contamination and persistent strains and to help in the implementation of
      corrective actions in food processing facilities to control the occurrence of
      this pathogenic bacterium. 

PMID- 25862046
TI  - Case study of the use of pulsed field gel electrophoresis in the detection of a
      food-borne outbreak.
AB  - In early July 2008, a cluster of six Salmonella Agona was identified in the
      Republic of Ireland. A dispersed, common source outbreak was suspected. Later in
      July a further case was identified and the Health Protection Agency in the UK
      indicated that they had 32 cases of S. Agona since Feb 2008. This chapter
      discusses how pulsed field gel electrophoresis was used to help confirm an
      outbreak and to trace the source of the outbreak. 

PMID- 25862047
TI  - Pulsed-field gel electrophoresis for Listeria monocytogenes.
AB  - Pulsed-Field Gel Electrophoresis (PFGE) is a molecular subtyping method with high
      discriminatory power, reproducibility, and epidemiological concordance for the
      subtyping of Listeria monocytogenes and other bacteria. PFGE uses rare-cutting
      restriction enzymes (macrorestriction) that cut the genomic DNA, usually
      resulting in 6-25 DNA fragments ranging between 30 and 600 kb. Bacterial cells
      are immobilized in agarose plugs and subsequently lysed to release genomic DNA,
      which is then subjected to DNA digestion. AscI and ApaI restriction enzymes are
      typically used for L. monocytogenes. Electrophoresis using an alternating
      electric field direction results in a DNA banding pattern, or fingerprint, which
      is used to classify isolates into different pulsotypes. PFGE is currently the
      CDC's gold standard method for epidemiological studies in foodborne outbreaks.

PMID- 25862048
TI  - Pulsed-field gel electrophoresis (PFGE) for pathogenic Cronobacter species.
AB  - Pulsed-field gel electrophoresis (PFGE) is a molecular-based subtyping strategy
      that uses a suitable DNA restriction endonuclease enzyme to cut genomic DNA into
      several large linear fragments, that can be separated based on their sizes. PFGE
      has been successfully applied to the subtyping of many pathogenic bacteria,
      including Cronobacter species, and it is commonly considered as a "gold standard"
      in epidemiological studies. 

PMID- 25862049
TI  - Pulsed-field gel electrophoresis of Bacillus cereus group strains.
AB  - Pulsed-Field Gel Electrophoresis (PFGE) subtyping has been used extensively to
      characterize various bacterial species and to facilitate comparative analysis of
      geographically diverse populations. To this end, standardized protocols for many
      different genera and species have been developed, particularly through the
      PulseNet platform. The Bacillus cereus group of bacteria includes a diverse
      species set, which are of particular importance in food safety as both human
      pathogens and spoilage organisms. The application of techniques to differentiate
      strains of B. cereus can be utilized to assist in both disease outbreak
      investigations, and also in strategies to monitor and control the organism in
      food production environments. This chapter describes a PFGE method, which may be
      applied to differentiate B. cereus strains. 

PMID- 25862050
TI  - Pulsed-field gel electrophoresis of Staphylococcus aureus.
AB  - For many bacterial pathogens, including Staphylococcus aureus, pulsed-field gel
      electrophoresis (PFGE) is a molecular typing method widely used in surveillance
      and epidemiological investigations. The general principle of PFGE involves
      creating large DNA fragments from intact bacterial chromosomes using rare cutting
      restriction endonucleases. These large DNA fragments are successfully separated
      in an agarose gel by alternating the direction of the electrical fields over a
      prolonged period of time. The resulting DNA banding patterns in the gel create a
      "DNA fingerprint," which can then be used to discriminate clonal relatedness of
      isolates based on set interpretation guidelines. Standardization of protocols has
      greatly enhanced the reproducibility of PFGE between labs, enabling national
      surveillance and further molecular epidemiological studies of S. aureus. 

PMID- 25862051
TI  - The use of pulsed-field gel electrophoresis for genotyping of Clostridium
      difficile.
AB  - Genotyping approaches are important for tracking infectious agents and can be
      used for various purposes. Pulsed-Field Gel Electrophoresis (PFGE) is among the
      highly discriminatory genotyping approaches commonly used for characterizing
      Clostridium difficile. Other genotyping methods used for C. difficile include
      Ribotyping, Restriction Endonuclease Assay (REA), Multilocus Variable Number
      Tandem Repeats (VNTR) Assay, and others. PFGE has a high discriminatory power,
      high reproducibility, and typeability. We utilized PFGE for typing C. difficile
      isolates of porcine and human origin. We used a macrorestriction fragment
      analysis of an intact genomic DNA using SmaI, a rare cutting restriction
      endonuclease. Using a Contour-Clamped Homogeneous Electric Field (CHEF) system
      with running conditions of 120 degrees  angle; initial switch time of 5 s; final
      switch time of 40 s with a run time of 18 h in a low-melting temperature agarose
      (Seakem Gold); and 0.5* TBE circulated in the CHEF system at 6 V/cm [CDC (2014)
      Pulsenet. http://www.cdc.gov/pulsenet/index.html . Accessed 22 Aug 2014]
      supported by 14  degrees C cooling module, we were able to separate very large
      DNA fragments (up to 2 Mb).

PMID- 25862052
TI  - Molecular subtyping of Clostridium botulinum by pulsed-field gel electrophoresis.
AB  - Pulsed-field gel electrophoresis (PFGE) has been extensively used to estimate the
      genetic diversity of Clostridium botulinum. In addition, PFGE is the standard
      method for investigating foodborne outbreaks associated with various enteric
      pathogens, including C. botulinum. PFGE can be used to exclude a suspected but
      not confirmed food source when the patterns of the food and clinical isolates are
      different. Indistinguishable PFGE patterns may also be useful for linking
      isolates between patients or to a food source, but results must be interpreted
      within an epidemiological context to ensure isolates are truly related. Here, we
      describe a standardized laboratory protocol for molecular subtyping of C.
      botulinum by PFGE.

PMID- 25862053
TI  - Pulsed-field gel electrophoresis of Yersinia pestis.
AB  - Yersinia pestis is a human pathogen and can cause serious disease. Biosafety
      level 3 (BSL3) is required when handling this microorganism and all work requires
      a biological safety cabinet. For pulsed-field gel electrophoresis (PFGE),
      dedicated BSL3 PFGE equipment or a documented procedure that ensures that all
      viable bacteria are inactivated is required. All plasticware and glassware that
      comes into contact with the cultures should be disinfected/sterilized or disposed
      of in a safe manner, according to the guidelines of institution. This includes
      decontamination of pipettes, spatulas, etc. that were in contact with the cell
      suspensions or plugs. Disinfection of reusable plug molds should be done before
      they are washed; the disposable plug molds, including the tape and the tab that
      was used to push the plugs out of the wells, are also contaminated and should be
      disinfected with 10 % bleach for at least 30 min if they will be washed and
      reused. 

PMID- 25862054
TI  - Pulsed field gel electrophoresis of group A streptococci.
AB  - Here we describe the protocols to perform PFGE analysis of chromosomal DNA from
      the bacterial species Streptococcus pyogenes (group A streptococcus, GAS) after
      digestion with the restriction enzyme SmaI. Large parts of the procedures are
      suitable for application to DNA digested with other restriction enzymes as well.
      We have put an effort to present extensions to solve possible limitations to the
      discriminatory power of the method in the specific case of S. pyogenes. 

PMID- 25862055
TI  - Application of pulsed field gel electrophoresis to type Campylobacter jejuni.
AB  - Pulsed field gel electrophoresis (PFGE) is generally accepted as one of the most
      discriminatory methods available for genotyping Campylobacter jejuni. PFGE has
      been extensively used in epidemiological studies, including outbreak
      investigation, persistence of genotypes in a human population, environmental
      diversity of sporadic infection isolates, dissemination of antibiotic-resistant
      strains, and comparison of genotypes within and between hosts. The main purpose
      of this chapter is to present a working PFGE protocol for those interested in
      incorporating this technique in their laboratories. 

PMID- 25862056
TI  - Pulsed-field gel electrophoresis of Pseudomonas aeruginosa.
AB  - Pulsed-field gel electrophoresis (PFGE) is a technique used for the separation of
      high molecular weight restriction fragments from digested bacterial genomic DNA
      on a gel matrix by applying an electric field that periodically changes
      direction. PFGE has been shown to be the most discriminatory and reproducible
      bacterial strain typing technique available. It is considered the 'gold standard'
      in epidemiological studies of pathogenic and nonpathogenic microorganisms. This
      chapter provides a detailed method for using PFGE in the genotyping of the
      opportunistic Gram-negative bacterial pathogen Pseudomonas aeruginosa.

PMID- 25862057
TI  - PFGE for Shiga toxin-producing Escherichia coli O157:H7 (STEC O157) and non-O157
      STEC.
AB  - This chapter describes the procedure of generating pulsed-field gel
      electrophoresis (PFGE) profiles (DNA fingerprints) of Shiga toxin-producing
      Escherichia coli O157:H7 (STEC O157) and non-O157 STEC strains within 48 h, based
      on the standardized laboratory protocol developed by the Centers for Disease
      Control and Prevention, USA. The protocol describes the preparation of agarose
      plugs containing STEC O157 and non-O157 STEC cells, the digestion of bacterial
      DNA in the plugs using restriction endonuclease enzymes, and the electrophoresis
      conditions to generate the characteristic PFGE profiles of STEC O157 and non-O157
      STEC isolates. 

PMID- 25862058
TI  - Pulsed-field gel electrophoresis of Salmonella enterica.
AB  - Pulsed-field gel electrophoresis (PFGE) is considered a "gold standard" for the
      molecular characterization of a number of bacterial strains. Its strength relies
      on its high discriminatory power, together with its high reproducibility. For
      many years, an international network, PulseNet International, allows the rapid
      comparison of PFGE data obtained all over the world, and it provides a valuable
      tool to promptly recognize the epidemiological dynamics of many pathogens,
      including Salmonella enterica. Here we describe the laboratory procedure to
      perform the standardized protocol for the PFGE typing of S. enterica strains. 

PMID- 25862059
TI  - PFGE protocols to distinguish subspecies of Lactococcus lactis.
AB  - Pulsed-field gel electrophoresis (PFGE), developed in the mid-1980s, rapidly
      became a "gold standard" method for analyzing bacterial chromosomes. Today,
      although outcompeted in resolution by alternative methods, such as optical
      mapping, and not applicable for high-throughput analyses, PFGE remains a valuable
      method for bacterial strain typing. Here, we describe optimized protocols for
      macrorestriction fingerprinting, characterization of plasmid complements, and
      gene localization by DNA-DNA hybridization of Lactococcus lactis genomes. 

PMID- 25862060
TI  - The use of PFGE method in genotyping of selected bacteria species of the
      Lactobacillus genus.
AB  - Bacteria belonging to the genus Lactobacillus are a group of microorganisms in
      which there are numerous strains with high probiotic potential. In recent years,
      interest in probiotics as nutritional supplements and as drugs has significantly
      increased. In order to carry out research on probiotic bacterial strains, their
      beneficial effects on the human body should be confirmed and molecular typing
      should be carried out with the aim of marking a specific strain. Pulse-field gel
      electrophoresis (PFGE) is the reference method employed for bacterial genotyping,
      but it is commonly used for typing mainly pathogenic bacteria. The following
      study describes a way of performing PFGE analysis in genotyping of bacteria
      species belonging to the genus Lactobacillus: L. fermentum, L. gasseri, L.
      plantarum and L. rhamnosus. 

PMID- 25862061
TI  - Pulsed-field gel electrophoresis for Leuconostoc mesenteroides and L.
      pseudomesenteroides.
AB  - Pulsed-field gel electrophoresis (PFGE) is a technique using alternating electric
      fields to help the separation of high molecular weight DNA fragments with a high
      resolution. This method consists of the digestion of bacterial chromosomal DNA
      with rare-cutting restriction enzymes and of applying an alternating electrical
      current between spatially distinct pairs of electrodes. DNA molecules migrate at
      different speeds according to the size of the fragment. This method is considered
      as the "gold standard" for genotyping, genetic fingerprinting, epidemiological
      studies, genome size estimation, and studying radiation-induced DNA damage and
      repair. 

PMID- 25862062
TI  - Pulsed field gel electrophoresis for Bifidobacterium.
AB  - Pulse Field Gel Electrophoresis (PFGE), unlike conventional electrophoresis, can
      resolve DNA fragments greater than 30 kb and is a highly discriminatory molecular
      typing method. Here we describe a PFGE protocol for bifidobacteria characterized
      by a short lysis time determined by the addition of lysis reagents to the initial
      cell suspension, a reduced incubation period of the plugs in proteinase K, and an
      improved washing plug step with preheating of the buffer in a shaking incubator. 

PMID- 25862063
TI  - Pulsed field gel electrophoresis for dairy propionibacteria.
AB  - Pulsed field gel electrophoresis (PFGE) is a technique using alternating electric
      fields to migrate high molecular weight DNA fragments with a high resolution.
      This method consists of the digestion of bacterial chromosomal DNA with rare
      cutting restriction enzymes and in applying an alternating electrical current
      between spatially distinct pairs of electrodes. DNA molecules migrate at
      different speeds according to the size of the fragments. Among other things, this
      technique is considered as the "gold standard" for genotyping, genetic
      fingerprinting, epidemiological studies, genome size estimation, and studying
      radiation-induced DNA damage and repair. This chapter describes a PFGE method
      that can be used to differentiate dairy propionibacteria. 

PMID- 25862064
TI  - In vitro evaluation of hypoglycemic agents to target human islet amyloid
      polypeptide: a key protein involved in amyloid deposition and beta-cell loss.
AB  - OBJECTIVES: Deposition of islet amyloid has been associated with beta-cell death,
      thereby furthering diabetes progression. Several hypoglycemic agents, such as
      thiazolidinediones, biguanide and dipeptidyl peptidase-4 inhibitors, have been
      known to preserve beta-cell mass, possibly by direct inhibition of islet amyloid
      formation. The general objective of this study was to evaluate the impact of the
      major representatives of hypoglycemic agents on amyloid formation by using in
      vitro molecular screening approaches. METHODS: Ten prototypical representatives
      of hypoglycemic agents were evaluated for the inhibition of amyloid formation in
      vitro using thioflavin fluorescence assays, far-ultraviolet circular dichroism,
      photo-induced cross linking assays and cell viability assays. RESULTS: Glyburide,
      repaglinide and troglitazone showed the highest potency in delaying and reducing
      fibril formation. Troglitazone, a thiazolidinedione, was the most effective agent
      abrogating amyloid fibril formation. Troglitazone affected the secondary
      structures of incubated human islet amyloid polypeptide (hIAPP). The circular
      dichroism spectra showed a delayed transition to the beta sheet conformation. A
      photo-induced cross-linking-based oligomerization assay demonstrated that
      repaglinide supressed the formation of hIAPP oligomers, whereas glyburide and
      troglitazone were ineffective in inhibiting oligomerization. Cell toxicity
      induced by hIAPP was reduced by all 3 compounds. CONCLUSION: This study provides
      new insights that could potentially identify new therapeutic strategies to impede
      the progression of pancreatic amyloidosis in human patients with type 2 diabetes.

PMID- 25862065
TI  - Ductal adenoma of breast: imaging characteristics and radiologic-pathologic
      correlation of unique findings which reflect "pseudoinvasion".
AB  - PURPOSE: To investigate the imaging characteristics of rare ductal adenoma of the
      breast, we evaluated the detailed imaging findings and correlated them with the
      pathologic features of the ductal adenomas. In particular, we describe in detail
      the imaging findings derived from "pseudoinvasion," one of the histological
      features unique to this tumor. MATERIALS AND METHODS: We reviewed the imaging
      findings including magnetic resonance imaging (MRI) in three patients with ductal
      adenomas of the breast and correlated the findings with the detailed histological
      features. RESULTS: All patients exhibited well-demarcated nodules with smooth
      margins on mammography. On ultrasonography, two patients exhibited mural nodules
      within cysts. The bases of mural nodules protruded into the mammary glands. On
      contrast-enhanced MRI, these margins were smooth. Histologically, the bases
      showed foci of tumor cells scattered into collagenous materials (pseudoinvasion),
      the tumor foci were located along the collagen fibers; therefore, the margins
      were smooth. CONCLUSIONS: Distinguishing ductal adenoma from invasive carcinoma
      is an urgent issue. A clear margin of 'pseudoinvasion' on MRI is both a unique
      finding and a useful diagnostic clue.

PMID- 25862066
TI  - Molecular epidemiology, and possible real-world applications in breast cancer.
AB  - Gene-environment interaction, a key idea in molecular epidemiology, has enabled
      the development of personalized medicine. This concept includes personalized
      prevention. While genome-wide association studies have identified a number of
      genetic susceptibility loci in breast cancer risk, however, the application of
      this knowledge to practical prevention is still underway. Here, we briefly review
      the history of molecular epidemiology and its progress in breast cancer
      epidemiology. We then introduce our experience with the trial combination of GWAS
      identified loci and well-established lifestyle and reproductive risk factors in
      the risk prediction of breast cancer. Finally, we report our exploration of the
      cumulative risk of breast cancer based on this risk prediction model as a
      potential tool for individual risk communication, including genetic risk factors
      and gene-environment interaction with obesity. 

PMID- 25862067
TI  - The effect of partial superficial parotidectomy on amplitude, latency and
      threshold of facial nerve stimulation.
AB  - The aim of this study is to assess the effect of partial superficial
      parotidectomy and facial nerve dissection to electrophysiologic parameters of
      intraoperative facial nerve monitoring such as nerve stimulation threshold,
      stimulus amplitude and latency. Twenty-five patients who underwent partial
      superficial parotidectomy for benign parotid gland mass were included in the
      study. After the identification of the facial nerve main trunk, minimum
      stimulation threshold, latencies and amplitudes of the orbicularis oculi
      (electrode 1) and orbicularis oris (electrode 2) electrodes at 0.50 milliamperes
      (mA) were recorded. All of the recordings were repeated after the completion of
      parotidectomy. Median nerve dissection duration was calculated and size of the
      tumors was measured during macroscopic pathology. The median minimum nerve
      stimulation threshold was 0.15 mA [interquartile range (IQR) = 0.05] before and
      0.15 mA (IQR = 0.08) after the parotidectomy (p = 0.02). Median nerve dissection
      duration was 49 min (IQR = 38). Median amplitude and latency in electrode 1
      before and after the facial nerve dissection were 322 millivolts (mV) (IQR =
      330), 370 mV (IQR = 370) (p = 0.02), 3 milliseconds (ms) (IQR = 1) and 4 ms (IQR
      = 2) (p = 0.05), respectively. Median amplitude and latency in electrode 2 before
      and after the facial nerve dissection were 396 mV (IQR = 275), 365 mV (IQR = 836)
      (p = 0.86), 3 ms (IQR = 1.5) and 4 ms (IQR = 1.5) (p = 0.17), respectively.
      Minimal nerve stimulation threshold and amplitude of electrode 1 were affected by
      facial nerve dissection among the electrophysiologic parameters (p = 0.02 and p =
      0.02). Of the electrophysiological parameters only the latency of electrode 2 was
      significantly correlated with tumor size (p = 0.03). Besides, none of the
      parameters were predictive for a possible postoperative facial nerve dysfunction
      regarding superficial partial parotidectomy. 

PMID- 25862068
TI  - A mechanostatistical approach to cortical bone remodelling: an equine model.
AB  - In this study, the development of a mechanostatistical model of three-dimensional
      cortical bone remodelling informed with in vivo equine data is presented. The
      equine model was chosen as it is highly translational to the human condition due
      to similar Haversian systems, availability of in vivo bone strain and biomarker
      data, and furthermore, equine models are recommended by the US Federal Drugs
      Administration for comparative joint research. The model was derived from micro
      computed tomography imaged specimens taken from the equine third metacarpal bone,
      and the Frost-based 'mechanostat' was informed from both in vivo strain gauges
      and biomarkers to estimate bone growth rates. The model also described the well
      known 'cutting cone' phenomena where Haversian canals tunnel and replace bone. In
      order to make this model useful in practice, a partial least squares regression
      (PLSR) surrogate model was derived based on training data from finite element
      simulations with different loads. The PLSR model was able to predict
      microstructure and homogenised Young's modulus with errors less than 2.2% and
      0.6%, respectively.

PMID- 25862069
TI  - 3D culture model of fibroblast-mediated collagen creep to identify abnormal cell
      behaviour.
AB  - Native collagen gels are important biomimetic cell support scaffolds, and a
      plastic compression process can now be used to rapidly remove fluid to any
      required collagen density, producing strong 3D tissue-like models. This study
      aimed to measure the mechanical creep properties of such scaffolds and to
      quantify any enhanced creep occurring in the presence of cells (cell-mediated
      creep). The test rig developed applies constant creep tension during culture and
      measures real-time extension due to cell action. This was used to model
      extracellular matrix creep, implicated in the transversalis fascia (TF) in
      inguinal hernia. Experiments showed that at an applied tension equivalent to 15%
      break strength, cell-mediated creep over 24-h culture periods was identified at
      creep rates of 0.46 and 0.38%/h for normal TF and human dermal fibroblasts,
      respectively. However, hernia TF fibroblasts produced negligible cell-mediated
      creep levels under the same conditions. Raising the cell culture temperature from
      4 to 37  degrees C was used to demonstrate live cell dependence of this creep.
      This represents the first in vitro demonstration of TF cell-mediated collagen
      creep and to our knowledge the first demonstration of a functional, hernia
      related cell abnormality.

PMID- 25862070
TI  - Optimal cutoffs for low skeletal muscle mass related to cardiovascular risk in
      adults: The Korea National Health and Nutrition Examination Survey 2009-2010.
AB  - The possible association between low skeletal muscle mass and cardiovascular
      disease (CVD) risk factors necessitates estimation of muscle mass even in
      subjects with normal body mass index (BMI). This study was aimed to investigate
      optimal cutoffs for skeletal muscle mass reflecting CVD risk factors and to
      evaluate the relationship between skeletal muscle mass and CVD risk factors in
      the general population and in subjects with normal BMI using these cutoffs. This
      cross-sectional study analyzed data from the Korea National Health and Nutrition
      Examination Survey 2009-2010. We enrolled 5120 men and 6559 women aged >=20
      years. Skeletal muscle index (SMI) was defined as the weight-adjusted
      appendicular skeletal muscle mass measured by dual-energy X-ray absorptiometry.
      Using receiver operating characteristic curve analyses, SMI cutoffs associated
      with CVD risk factors were determined. Lower SMI was significantly associated
      with an increased prevalence of CVD risk factors. The first cutoffs in men and
      women were 32 and 25%, respectively, and the second cutoffs were 30 and 23.5%.
      Subjects in stage I and stage II SMI categories showed increased prevalence and
      risk for several CVD risk factors. These tendencies persisted in the association
      between cardiometabolic characteristics and SMI even in subjects with normal BMI.
      Using cutoffs of low skeletal muscle mass reflecting CVD risk factors, lower
      skeletal muscle mass was associated with increased prevalence and risk of several
      CVD risk factors. A higher prevalence of cardiometabolic abnormalities was
      observed among subjects with normal BMI but low skeletal muscle mass.

PMID- 25862071
TI  - Obstructive sleep apnea and acute respiratory failure: An analysis of mortality
      risk in patients with pneumonia requiring invasive mechanical ventilation.
AB  - PURPOSE: Although obstructive sleep apnea (OSA) is common and pneumonia is a
      frequent cause of acute respiratory failure requiring admission to the intensive
      care unit, little is known about the effect of OSA on this patient population.
      This study examined outcomes associated with OSA in patients with pneumonia
      requiring invasive mechanical ventilation. MATERIALS AND METHODS: The Nationwide
      Inpatient Sample was investigated for discharges with a primary diagnosis of
      pneumonia requiring invasive mechanical ventilation between 2009 and 2011.
      Persons aged 18 to 75 years with OSA were compared with patients without OSA.
      Outcomes included in-hospital mortality and nonroutine discharges. RESULTS: Among
      74032 hospitalizations, 13.8% (10227) were obese, and 10.3% (7610) had OSA.
      Obstructive sleep apnea patients had decreased in-hospital mortality (17.0% vs
      25.8%; P < .01) and nonroutine discharge (74.4% vs 79.4%; P < .01) when compared
      with non-OSA patients. In adjusted logistic models, OSA was associated with a 27%
      decreased risk of in-hospital mortality (odds ratio, 0.73; 95% confidence
      interval, 0.68-0.79; P < .01) and a 21% decreased risk of nonroutine discharge
      (odds ratio, 0.79; 95% confidence interval, 0.74-0.84; P < .01). CONCLUSIONS: In
      mechanically ventilated patients with pneumonia, OSA was associated decreased in
      hospital mortality and nonroutine discharge. It is possible that differences in
      treatment pattern may partially explain improved survival.

PMID- 25862072
TI  - Development of a nanoparticle-based oral vaccine for Atlantic salmon against ISAV
      using an alphavirus replicon as adjuvant.
AB  - Adjuvants used in vaccine aquaculture are frequently harmful for the fish,
      causing melanosis, granulomas and kidney damage. Along with that, vaccines are
      mostly administered by injection, causing pain and stress to the fish. We used
      the DNA coding for the replicase of alphavirus as adjuvant (Ad) of a vaccine
      against ISAV. The Ad and an inactivated ISAV (V) were loaded in chitosan
      nanoparticles (NPs) to be administered orally to Atlantic salmon. NP-Ad was able
      to deliver the DNA ex vivo and in vivo. Oral administration of the NPs stimulated
      the expression of immune molecules, but did not stimulate the humoral response.
      Although the vaccination with NP-V results in a modest protection of fish against
      ISAV, NP-V administered together with NP-Ad caused a protection of 77%.
      Therefore, the DNA coding for the replicase of alphavirus could be administered
      orally and can potentiate the immuneprotection of a virine against infection.

PMID- 25862073
TI  - A critical analysis of the literature and theoretical perspectives on theory
      practice gap amongst newly qualified nurses within the United Kingdom.
AB  - OBJECTIVES: This critical analysis of the literature examines the factors and
      theoretical perspectives contributing to the theory-practice gap for newly
      qualified nurses within the United Kingdom. This article aspires to inform, guide
      and promote effective nursing education both academically and practically.
      DESIGN: A systematic search strategy was conducted to identify relevant
      literature covering the period of 2000-2014, to include only contemporary
      theoretical perspectives coinciding with the dearth of contemporary literature
      post Project 2000. DATA SOURCES: The literature was systematically investigated
      utilising nursing research databases, the Cumulative Index of Nursing and Allied
      Health Literature, Allied and Complementary Medicine, the U.S. National Library
      of Medicine and Internurse. REVIEW METHODS: To satisfy the search criteria only
      articles conducted within the United Kingdom and written in the English language
      were included. Only literature including nurses and newly qualified nurses were
      included. To identify relevant literature a series of key words were utilised.
      RESULTS: Systematic review of the literature revealed that newly qualified nurses
      feel unprepared for practice, lacking confidence in their own abilities. It was
      also felt by newly qualified nurses that not enough time was dedicated to the
      production of clinical skills during their training. The use of preceptorship
      programmes was found to reduce the transitional stress associated with becoming a
      qualified nursing practitioner. CONCLUSIONS: Despite the increasing research
      being undertaken in the area of theory-practice gap there is still a need for
      nursing educators, practice areas and regulatory bodies to invest further in
      research. The effects of preceptorship and simulation exercises in particular
      require more research to provide regulatory bodies with enough evidence to make
      an informed decision as to whether their use should be mandatory.

PMID- 25862074
TI  - Letting go: How newly graduated registered nurses in Western Canada decide to
      exit the nursing profession.
AB  - BACKGROUND: The Canadian Nurses Association (CNA) estimates a nursing shortage in
      Canada will rise to 60,000 registered nurses by 2022. Further compounding this
      crisis is the approximate 14-61% of new nursing graduates who will change nursing
      roles or exit the profession. AIM: To explore the factors and basic psychosocial
      process involved in the decisions of newly graduated registered nurses in Western
      Canada who permanently exit the nursing profession within five years. DESIGN:
      Data was collected through unstructured and semi-structured interviews using the
      Glaserian grounded theory method. FINDINGS: Participants were found to be in a
      process of letting go of nursing that commenced as students and continued as they
      entered practice as registered nurses. Four major themes were identified. 1)
      Navigating constraints of the healthcare system and workplace: participants
      encountered difficulties adjusting to shiftwork and workload. 2) Negotiating
      social relationships, hierarchies, and troublesome behaviors; specifically
      hierarchal and horizontal violence. 3) Facing fears, traumas and challenges. 4)
      Weighing competing rewards and tensions which resulted in leaving the nursing
      profession. CONCLUSION: Students and subsequently new nursing graduates require a
      variety of supports to establish a nursing identity and remain in the profession.
      These supports include a manageable workload; meaningful orientation;
      interprofessional teamwork; and engagement within transformational and authentic
      leadership constructs. New nurses require a sense of being welcomed, valued,
      respected and accepted into the workplace environment, as well as constructive
      feedback, emotional support and debriefing to face workplace challenges.

PMID- 25862075
TI  - Can We Predict Functional Outcome in Neonates with Hypoxic Ischemic
      Encephalopathy by the Combination of Neuroimaging and Electroencephalography?
AB  - BACKGROUND: Neonatal hypoxic ischemic encephalopathy (HIE) is a major cause of
      mortality, morbidity, and long-term neurological deficits. Despite the
      availability of neuroimaging and neurophysiological testing, tools for accurate
      early diagnosis and prediction of developmental outcome are still lacking. The
      goal of this study was to determine if combined use of magnetic resonance imaging
      (MRI) and electroencephalography (EEG) findings could support outcome prediction.
      METHODS: We retrospectively reviewed records of 17 HIE neonates, classified brain
      MRI and EEG findings based on severity, and assessed clinical outcome up to 48
      months. We determined the relation between MRI/EEG findings and clinical outcome.
      RESULTS: We demonstrated a significant relationship between MRI findings and
      clinical outcome (Fisher's exact test, p = 0.017). EEG provided no additional
      information about the outcome beyond that contained in the MRI score. The
      statistical model for outcome prediction based on random forests suggested that
      EEG readings at 24 hours and 72 hours could be important variables for outcome
      prediction, but this needs to be investigated further. CONCLUSION: Caution should
      be used when discussing prognosis for neonates with mild-to-moderate HIE based on
      early MR imaging and EEG findings. A robust, quantitative marker of HIE severity
      that allows for accurate prediction of long-term outcome, particularly for mild
      to-moderate cases, is still needed.

PMID- 25862076
TI  - Bacillary replication and macrophage necrosis are determinants of neutrophil
      recruitment in tuberculosis.
AB  - We previously determined that burst size necrosis is the chief mode of
      mononuclear cell death in the lungs of mice with tuberculosis. The present study
      explored the link between infection-induced necrosis of mononuclear phagocytes
      and neutrophil accumulation in the lungs of mice challenged with one of four
      Mycobacterium tuberculosis strains of increasing virulence (RvDeltaphoPR mutant,
      H37Ra, H37Rv and Erdman). At all time points studied, Erdman produced the highest
      bacterial load and the highest proportion and number of M. tuberculosis-infected
      neutrophils. These parameters, and the proportion of TUNEL-positive cells,
      tracked with virulence across all strains tested. Differences in neutrophil
      infection were not reflected by levels of chemoattractant cytokines in
      bronchoalveolar lavage fluid, while interferon-gamma (reported to suppress
      neutrophil trafficking to the lung in tuberculosis) was highest in Erdman
      infected mice. Treating Erdman-infected mice with ethambutol decreased the
      proportion of mononuclear phagocytes with high bacterial burden and the ratio of
      infected neutrophils to infected mononuclear cells in a dose-dependent manner. We
      propose that faster replicating M. tuberculosis strains cause more necrosis which
      in turn promotes neutrophil recruitment. Neutrophils infected with M.
      tuberculosis constitute a biomarker for poorly controlled bacterial replication,
      infection-induced mononuclear cell death, and increased severity of immune
      pathology in tuberculosis. 

PMID- 25862078
TI  - Social and vocal behavior in adult greater tube-nosed bats (Murina leucogaster).
AB  - Many studies have revealed the significant influence of the social nature and
      ecological niche of a species on the design and complexity of their communication
      sounds. The knowledge of communication sounds and particularly of the flexibility
      in their use among mammals, however, remains patchy. Being highly vocal and
      social, bats are well suited for investigating vocal plasticity as well as vocal
      diversity. Thus, the overall aim of this study was to test the presence of
      structural overlap between calls used in social communication and echolocation
      pulses emitted during foraging in greater tube-nosed bats (Murina leucogaster).
      Acoustic analysis and spectrotemporal decomposition of calls revealed a rich
      communication repertoire comprising 12 simple syllables and 5 composites with
      harmonics in the ultrasonic range. Simultaneous recording of vocal and social
      behavior in the same species yielded a strong correspondence between distinct
      behaviors and specific call types in support of Morton's motivation-structure
      hypothesis. Spectrographic analysis of call types also revealed the presence of
      modified components of echolocation pulses embedded within social calls.
      Altogether, the data suggest that bats can parse complex sounds into structurally
      simpler components that are recombined within behaviorally meaningful and
      multifunctional contexts. 

PMID- 25862077
TI  - Beyond microbial community composition: functional activities of the oral
      microbiome in health and disease.
AB  - The oral microbiome plays a relevant role in the health status of the host and is
      a key element in a variety of oral and non-oral diseases. Despite advances in our
      knowledge of changes in microbial composition associated with different health
      conditions the functional aspects of the oral microbiome that lead to dysbiosis
      remain for the most part unknown. In this review, we discuss the progress made
      towards understanding the functional role of the oral microbiome in health and
      disease and how novel technologies are expanding our knowledge on this subject. 

PMID- 25862079
TI  - The allele frequency of CYP2A6*4 in four ethnic groups of China.
AB  - The CYP2A6*4 allele, characterized as the whole deletion of this gene, is closely
      associated with nicotine dependence, cancer susceptibility, and drug
      responsiveness. The frequency of this molecular variant differs across
      populations. Although genetic polymorphisms of CYP2A6*4 and its functional
      results have been reported in Chinese Han population, the allele frequency of
      CYP2A6*4 was largely unknown in other Chinese ethnic population. In this study,
      we investigated the allele frequency of CYP2A6*4 in four main ethnic groups of
      China based on our newly developed quantitative real-time PCR assay. The
      frequencies of the CYP2A6*4 allele were 7.9%, 15%, 0% and 2% in Han (N=120),
      Uighur (N=100), Bouyei (N=100) and Tibetan (N=100) (P<0.0001), respectively. This
      work greatly expanded our understanding of the distribution of CYP2A6*4 in
      Chinese population and provided more information of different ethnic population's
      smoking behavior and also in disease susceptibility and drug response. 

PMID- 25862081
TI  - A method for in-gel fluorescent visualization of proteins after native and sodium
      dodecyl sulfate polyacrylamide gel electrophoresis.
AB  - We have developed a simple one-step 30-min method for fluorescent visualization
      of proteins in native and sodium dodecyl sulfate polyacrylamide gel
      electrophoresis (PAGE) gels. The method is based on formation of strong
      fluorophores via potassium ferricyanide-provoked oxidation of tryptophan (Trp).
      Following PAGE, gels are soaked in water solution of potassium ferricyanide (100
      mM) and NaOH (1 M) and are kept in the dark for 30 min. Gels are then transferred
      to water and scanned. The sensitivity of the method was slightly lower compared
      with standard Coomassie Brilliant Blue (CBB) staining. The method can be useful
      when rapid acquisition of data is of the essence. After preview, gels can be post
      stained using the CBB protocol for further analysis. The intensity of
      fluorescence is dependent on Trp number, so the protocol might find application
      in the quantification of Trp residues as illustrated here. Importantly, there is
      room for improvement of the method. Namely, according to excitation-emission
      matrix analysis of stained protein bands, maximal fluorescence intensity (at
      345/460 nm) was 3.5-fold higher compared with the settings that were available on
      a commercial imager (395/525 nm). As a supplement, we present an upgrade of the
      previously described method for in-gel detection of non-heme iron-binding
      proteins that also employs potassium ferricyanide.

PMID- 25862080
TI  - Z-scan fluorescence profile deconvolution of cytosolic and membrane-associated
      protein populations.
AB  - This study introduces a technique that characterizes the spatial distribution of
      peripheral membrane proteins that associate reversibly with the plasma membrane.
      An axial scan through the cell generates a z-scan intensity profile of a
      fluorescently labeled peripheral membrane protein. This profile is analytically
      separated into membrane and cytoplasmic components by accounting for both the
      cell geometry and the point spread function. We experimentally validated the
      technique and characterized both the resolvability and stability of z-scan
      measurements. Furthermore, using the cellular brightness of green fluorescent
      protein, we were able to convert the fluorescence intensities into concentrations
      at the membrane and in the cytoplasm. We applied the technique to study the
      translocation of the pleckstrin homology domain of phospholipase C delta 1
      labeled with green fluorescent protein on ionomycin treatment. Analysis of the z
      scan fluorescence profiles revealed protein-specific cell height changes and
      allowed for comparison between the observed fluorescence changes and predictions
      based on the cellular surface area-to-volume ratio. The quantitative capability
      of z-scan fluorescence profile deconvolution offers opportunities for
      investigating peripheral membrane proteins in the living cell that were
      previously not accessible.

PMID- 25862082
TI  - Method for collecting and immobilizing individual cumulus cells enabling
      quantitative immunofluorescence analysis of proteins.
AB  - Most immunofluorescence methods rely on techniques dealing with a very large
      number of cells. However, when the number of cells in a sample is low (e.g., when
      cumulus cells must be analyzed from individual cumulus-oocyte complexes),
      specific techniques are required to conserve, fix, and analyze cells
      individually. We established and validated a simple and effective method for
      collecting and immobilizing low numbers of cumulus cells that enables easy and
      quick quantitative immunofluorescence analysis of proteins from individual cells.
      To illustrate this technique, we stained proprotein of a disintegrin and
      metalloproteinase with thrombospondin-like repeats-1 (proADAMTS-1) and analyzed
      its levels in individual porcine cumulus cells.

PMID- 25862083
TI  - Monitoring channel activities of proteoliposomes with SecA and Cx26 gap junction
      in single oocytes.
AB  - Establishing recordable channels in membranes of oocytes formed by expressing
      exogenous complementary DNA (cDNA) or messenger RNA (mRNA) has contributed
      greatly to understanding the molecular mechanisms of channel functions. Here, we
      report the extension of this semi-physiological system for monitoring the channel
      activity of preassembled membrane proteins in single cell oocytes by injecting
      reconstituted proteoliposomes along with substrates or regulatory molecules. We
      build on the observation that SecA from various bacteria forms active protein
      conducting channels with injection of proteoliposomes, protein precursors, and
      ATP-Mg(2+). Such activity was enhanced by reconstituted SecYEG-SecDF*YajC
      liposome complexes that could be monitored easily and efficiently, providing
      correlation of in vitro and intact cell functionality. In addition, inserting
      reconstituted gap junction Cx26 liposomes into the oocytes allowed the
      demonstration of intracellular/extracellular Ca(2+)-regulated hemi-channel
      activities. The channel activities can be detected rapidly after injection, can
      be monitored for various effectors, and are dependent on specific exogenous lipid
      compositions. This simple and effective functional system with low endogenous
      channel activity should have broad applications for monitoring the specific
      channel activities of complex interactions of purified membrane proteins with
      their effectors and regulatory molecules.

PMID- 25862084
TI  - Single unit filter-aided method for fast proteomic analysis of tear fluid.
AB  - Human tear fluid is a complex mixture containing high concentrations of proteins
      and is increasingly becoming an important source for studying protein biomarkers
      of eye-related diseases such as Graves' ophthalmopathy. Today, the Schirmer tear
      test is the most widely used technique for tear collection. However, sample
      handling and protein extraction from these strips have been highly challenging.
      Cutting and removal of the Schirmer strips after extraction, which may lead to
      sample loss prior to downstream analysis, are some of the challenges to consider.
      To address some of these limitations, we have developed a single-unit filter
      aided method for both sample handling and protein extraction. In addition, we
      systematically investigated the most suitable conditions for protein extraction
      from these strips. Among the different extraction conditions applied, extraction
      with 100 mM ammonium bicarbonate containing 50 mM NaCl resulted in the highest
      number of identified proteins using one-dimensional liquid chromatography tandem
      mass spectrometry (LC-MS/MS). Moreover, 1526 proteins were identified when the
      optimized extraction method was combined with two-dimensional LC-MS/MS analysis,
      demonstrating the applicability of this novel approach to the study of the tear
      proteome. This dataset of identified proteins represents a comprehensive
      catalogue of the tear proteome and may serve as a list for future biomarker
      research.

PMID- 25862085
TI  - Development of in vitro PIK3C3/VPS34 complex protein assay for autophagy-specific
      inhibitor screening.
AB  - Autophagy is an important catabolic program to respond to a variety of cellular
      stresses by forming a double membrane vesicle, autophagosome. Autophagy plays key
      roles in various cellular functions. Accordingly, dysregulation of autophagy is
      closely associated with diseases such as diabetes, neurodegenerative diseases,
      cardiomyopathy, and cancer. In this sense, autophagy is emerging as an important
      therapeutic target for disease control. Among the autophagy machineries,
      PIK3C3/VPS34 complex functions as an autophagy-triggering kinase to recruit the
      subsequent autophagy protein machineries on the phagophore membrane. Accumulating
      evidence showing that inhibition of PIK3C3/VPS34 complex successfully inhibits
      autophagy makes the complex an attractive target for developing autophagy
      inhibitors. However, one concern about PIK3C3/VPS34 complex is that many
      different PIK3C3/VPS34 complexes have distinct cellular functions. In this study,
      we have developed an in vitro PIK3C3/VPS34 complex monitoring assay for autophagy
      inhibitor screening in a high-throughput assay format instead of targeting the
      catalytic activity of the PIK3C3/VPS34 complex, which shuts down all PIK3C3/VPS34
      complexes. We performed in vitro reconstitution of an essential autophagy
      promoting PIK3C3/VPS34 complex, Vps34-Beclin1-ATG14L complex, in a microwell
      plate (96-well format) and successfully monitored the complex formation in many
      different conditions. This PIK3C3/VPS34 complex protein assay would provide a
      reliable tool for the screening of autophagy-specific inhibitors.

PMID- 25862086
TI  - Robust regression methods for real-time polymerase chain reaction.
AB  - Current real-time polymerase chain reaction (PCR) data analysis methods implement
      linear least squares regression methods for primer efficiency estimation based on
      standard curve dilution series. This method is sensitive to outliers that distort
      the outcome and are often ignored or removed by the end user. Here, robust
      regression methods are shown to provide a reliable alternative because they are
      less affected by outliers and often result in more precise primer efficiency
      estimators than the linear least squares method. 

PMID- 25862087
TI  - On the use of an appropriate TdT-mediated dUTP-biotin nick end labeling assay to
      identify apoptotic cells.
AB  - Apoptosis is an essential cellular mechanism involved in many processes such as
      embryogenesis, metamorphosis, and tissue homeostasis. DNA fragmentation is one of
      the key markers of this form of cell death. DNA fragmentation is executed by
      endogenous endonucleases such as caspase-activated DNase (CAD) in caspase
      dependent apoptosis. The TUNEL (TdT-mediated dUTP-biotin nick end labeling)
      technique is the most widely used method to identify apoptotic cells in a tissue
      or culture and to assess drug toxicity. It is based on the detection of 3'-OH
      termini that are labeled with dUTP by the terminal deoxynucleotidyl transferase.
      Although the test is very reliable and sensitive in caspase-dependent apoptosis,
      it is completely useless when cell death is mediated by pathways involving DNA
      degradation that generates 3'-P ends as in the LEI/L-DNase II pathway. Here, we
      propose a modification in the TUNEL protocol consisting of a dephosphorylation
      step prior to the TUNEL labeling. This allows the detection of both types of DNA
      breaks induced during apoptosis caspase-dependent and independent pathways,
      avoiding underestimating the cell death induced by the treatment of interest.

PMID- 25862088
TI  - Aberrant high frequency oscillations recorded in the rat nucleus accumbens in the
      methylazoxymethanol acetate neurodevelopmental model of schizophrenia.
AB  - BACKGROUND: Altered activity of the nucleus accumbens (NAc) is thought to be a
      core feature of schizophrenia and animal models of the disease. Abnormal high
      frequency oscillations (HFO) in the rat NAc have been associated with
      pharmacological models of schizophrenia, in particular the N-methyl-d-aspartate
      receptor (NMDAR) hypofunction model. Here, we tested the hypothesis that abnormal
      HFO are also associated with a neurodevelopmental rat model. METHODS: Using
      prenatal administration of the mitotoxin methylazoxymethanol acetate (MAM) we
      obtained the offspring MAM rats. Adult MAM and Sham rats were implanted with
      electrodes, for local field potential recordings, in the NAc. RESULTS:
      Spontaneous HFO (spHFO) in MAM rats were characterized by increased power and
      frequency relative to Sham rats. MK801 dose-dependently increased the power of
      HFO in both groups. However, the dose-dependent increase in HFO frequency found
      in Sham rats was occluded in MAM rats. The antipsychotic compound, clozapine
      reduced the frequency of HFO which was similar in both MAM and Sham rats.
      Further, HFO were modulated in a similar manner by delta oscillations in both MAM
      and Sham rats. CONCLUSION: Together these findings suggest that increased HFO
      frequency represents an important feature in certain animal models of
      schizophrenia. These findings support the hypothesis that altered functioning of
      the NAc is a core feature in animal models of schizophrenia.

PMID- 25862089
TI  - Homeostatic NF-kappaB Signaling in Steady-State Migratory Dendritic Cells
      Regulates Immune Homeostasis and Tolerance.
AB  - Migratory non-lymphoid tissue dendritic cells (NLT-DCs) transport antigens to
      lymph nodes (LNs) and are required for protective immune responses in the context
      of inflammation and to promote tolerance to self-antigens in steady-state.
      However, the molecular mechanisms that elicit steady-state NLT-DC maturation and
      migration are unknown. By comparing the transcriptome of NLT-DCs in the skin with
      their migratory counterparts in draining LNs, we have identified a novel NF
      kappaB-regulated gene network specific to migratory DCs. We show that targeted
      deletion of IKKbeta in DCs, a major activator of NF-kappaB, prevents NLT-DC
      accumulation in LNs and compromises regulatory T cell conversion in vivo. This
      was associated with impaired tolerance and autoimmunity. NF-kappaB is generally
      considered the prototypical pro-inflammatory transcription factor, but this study
      describes a role for NF-kappaB signaling in DCs for immune homeostasis and
      tolerance that could have implications in autoimmune diseases and immunity.

PMID- 25862090
TI  - Lipopolysaccharide Induces Alveolar Macrophage Necrosis via CD14 and the P2X7
      Receptor Leading to Interleukin-1alpha Release.
AB  - Acute lung injury (ALI) remains a serious health issue with little improvement in
      our understanding of the pathophysiology and therapeutic approaches. We
      investigated the mechanism that lipopolysaccharide (LPS) induces early neutrophil
      recruitment to lungs and increases pulmonary vascular permeability during ALI.
      Intratracheal LPS induced release of pro-interleukin-1alpha (IL-1alpha) from
      necrotic alveolar macrophages (AM), which activated endothelial cells (EC) to
      induce vascular leakage via loss of vascular endothelial (VE)-cadherin. LPS
      triggered the AM purinergic receptor P2X7(R) to induce Ca(2+) influx and ATP
      depletion, which led to necrosis. P2X7R deficiency significantly reduced necrotic
      death of AM and release of pro-IL-1alpha into the lung. CD14 was required for LPS
      binding to P2X7R, as CD14 neutralization significantly diminished LPS induced
      necrotic death of AM and pro-IL-1alpha release. These results demonstrate a key
      role for pro-IL-1alpha from necrotic alveolar macrophages in LPS-mediated ALI, as
      a critical initiator of increased vascular permeability and early neutrophil
      infiltration. 

PMID- 25862091
TI  - The methylcytosine dioxygenase Tet2 promotes DNA demethylation and activation of
      cytokine gene expression in T cells.
AB  - Epigenetic regulation of lineage-specific genes is important for the
      differentiation and function of T cells. Ten-eleven translocation (Tet) proteins
      catalyze 5-methylcytosine (5 mC) conversion to 5-hydroxymethylcytosine (5 hmC) to
      mediate DNA demethylation. However, the roles of Tet proteins in the immune
      response are unknown. Here, we characterized the genome-wide distribution of 5
      hmC in CD4(+) T cells and found that 5 hmC marks putative regulatory elements in
      signature genes associated with effector cell differentiation. Moreover, Tet2
      protein was recruited to 5 hmC-containing regions, dependent on lineage-specific
      transcription factors. Deletion of Tet2 in T cells decreased their cytokine
      expression, associated with reduced p300 recruitment. In vivo, Tet2 plays a
      critical role in the control of cytokine gene expression in autoimmune disease.
      Collectively, our findings suggest that Tet2 promotes DNA demethylation and
      activation of cytokine gene expression in T cells.

PMID- 25862093
TI  - Quadruple valve replacement and bypass surgery 23 years after the Ross
      operation?.
AB  - This report describes a case of simultaneous quadruple valve replacement,
      coronary artery bypass surgery and reconstruction of one aortic sinus performed
      in a patient who had undergone the Ross operation 23 years previously. 

PMID- 25862092
TI  - Distinct Commensals Induce Interleukin-1beta via NLRP3 Inflammasome in
      Inflammatory Monocytes to Promote Intestinal Inflammation in Response to Injury.
AB  - The microbiota stimulates inflammation, but the signaling pathways and the
      members of the microbiota involved remain poorly understood. We found that the
      microbiota induces interleukin-1beta (IL-1beta) release upon intestinal injury
      and that this is mediated via the NLRP3 inflammasome. Enterobacteriaceae and in
      particular the pathobiont Proteus mirabilis, induced robust IL-1beta release that
      was comparable to that induced by the pathogen Salmonella. Upon epithelial
      injury, production of IL-1beta in the intestine was largely mediated by
      intestinal Ly6C(high) monocytes, required chemokine receptor CCR2 and was
      abolished by deletion of IL-1beta in CCR2(+) blood monocytes. Furthermore,
      colonization with P. mirabilis promoted intestinal inflammation upon intestinal
      injury via the production of hemolysin, which required NLRP3 and IL-1 receptor
      signaling in vivo. Thus, upon intestinal injury, selective members of the
      microbiota stimulate newly recruited monocytes to induce NLRP3-dependent IL-1beta
      release, which promotes inflammation in the intestine.

PMID- 25862094
TI  - Chitosan tubes can restore the function of resected phrenic nerves.
AB  - OBJECTIVES: We previously reported that the phrenic nerve could be
      morphologically repaired by implantation of a chitosan nanofibre tube (C-tube).
      In the current study, we investigated whether implantation of C-tubes could
      improve the function of an injured phrenic nerve using a beagle dog model.
      METHODS: Seven beagle dogs underwent right thoracotomy under general anaesthesia.
      An approximately 5 mm length of the right phrenic nerve was resected. Five dogs
      had a C-tube implantation (C-tube group) and other two dogs did not have the C
      tube implantation (control group). Diaphragm movements were longitudinally
      measured by X-ray fluoroscopy before surgery, immediately after the surgery, and
      3, 6 and 12 months after the surgery. The diaphragm movement was determined by
      diaphragm levels at inspiration and expiration phases, and the excursion
      difference between them was calculated. At 12 months after the surgery,
      rethoracotomy was performed to examine electrical phrenic nerve conduction. The C
      tube and phrenic nerve were then excised for histological assessment of nerve
      regeneration. RESULTS: Three of the five animals of the C-tube group showed
      improvement of diaphragm movement with time. In these three animals, slow phrenic
      nerve conduction was observed. Histological assessment showed that the injured
      nerve was connected by newly regenerating nerve fibres surrounded by granulation
      tissue within the C-tube. On the other hand, the animals in the control group and
      two animals of the C-tube group showed neither improved diaphragm movement, nor
      electrical conduction to the diaphragm. No nerve fibre regeneration was found by
      histology. CONCLUSIONS: Our results suggest that, in addition to morphological
      improvement, C-tube implantation can functionally improve the injured phrenic
      nerve by promoting phrenic nerve regeneration.

PMID- 25862095
TI  - Successful management of oesophageal conduit necrosis by a single-stage
      reconstruction with the pedicled pectoralis major myocutaneous flap.
AB  - Conduit necrosis is a rare but potentially devastating complication of
      oesophageal surgery and the subsequent reversal of oesophageal discontinuity can
      be challenging. An option for both cervical-oesophageal reconstruction and neck
      wound closure has been limited and less successful. We report a patient with
      colon conduit necrosis and cervical-oesophageal discontinuity whose cervial
      oesophagus was successfully reconstructed with a single-stage pedicled pectoralis
      major myocutaneous flap and neck wound closure. 

PMID- 25862096
TI  - Impact of body tilt on the central aortic pressure pulse.
AB  - The present work was undertaken to investigate, in young healthy volunteers, the
      relationships between the forward propagation times of arterial pressure waves
      and the timing of reflected waves observable on the aortic pulse, in the course
      of rapid changes in body position. 20 young healthy subjects, 10 men, and 10
      women, were examined on a tilt table at two different tilt angles, -10 degrees 
      (Head-down) and + 45 degrees  (Head-up). In each position, carotid-femoral (Tcf)
      and carotid-tibial forward propagation times (Tct) were measured with the
      Complior device. In each position also, the central aortic pressure pulse was
      recorded with radial tonometry, using the SphygmoCor device and a generalized
      transfer function, so as to evaluate the timing of reflected waves reaching the
      aorta in systole (onset of systolic reflected wave, sT1r) and diastole (mean
      transit time of diastolic reflected wave, dMTT). The position shift from Head-up
      to Head-down caused a massive increase in both Tct (women from 130 +/- 10 to 185
      +/- 18 msec P < 0.001, men from 136 +/- 9 to 204 +/- 18 msec P < 0.001) and dMTT
      (women from 364 +/- 35 to 499 +/- 33 msec P < 0.001, men from 406 +/- 22 to 553
      +/- 21 msec P < 0.001). Mixed model regression showed that the changes in Tct and
      dMTT observed between Head-up and Head-down were tightly coupled (regression
      coefficient 2.1, 95% confidence interval 1.9-2.3, P < 0.001). These results
      strongly suggest that the diastolic waves observed on central aortic pulses
      reconstructed from radial tonometric correspond at least in part to reflections
      generated in the lower limbs. 

PMID- 25862097
TI  - In vivo structure-function studies of human hepatic lipase: the catalytic
      function rescues the lean phenotype of HL-deficient (hl-/-) mice.
AB  - The lean body weight phenotype of hepatic lipase (HL)-deficient mice (hl(-/-))
      suggests that HL is required for normal weight gain, but the underlying
      mechanisms are unknown. HL plays a unique role in lipoprotein metabolism
      performing bridging as well as catalytic functions, either of which could
      participate in energy homeostasis. To determine if both the catalytic and
      bridging functions or the catalytic function alone are required for the effect of
      HL on body weight, we studied (hl(-/-)) mice that transgenically express
      physiologic levels of human (h)HL (with catalytic and bridging functions) or a
      catalytically-inactive (ci)HL variant (with bridging function only) in which the
      catalytic Serine 145 was mutated to Alanine. As expected, HL activity in
      postheparin plasma was restored to physiologic levels only in hHL-transgenic mice
      (hl(-/-)hHL). During high-fat diet feeding, hHL-transgenic mice exhibited
      increased body weight gain and body adiposity relative to hl(-/-)ciHL mice. A
      similar, albeit less robust effect was observed in female hHL-transgenic relative
      to hl(-/-)ciHL mice. To delineate the basis for this effect, we determined
      cumulative food intake and measured energy expenditure using calorimetry.
      Interestingly, in both genders, food intake was 5-10% higher in hl(-/-)hHL mice
      relative to hl(-/-)ciHL controls. Similarly, energy expenditure was ~10% lower in
      HL-transgenic mice after adjusting for differences in total body weight. Our
      results demonstrate that (1) the catalytic function of HL is required to rescue
      the lean body weight phenotype of hl(-/-) mice; (2) this effect involves
      complementary changes in both sides of the energy balance equation; and (3) the
      bridging function alone is insufficient to rescue the lean phenotype of hl(-/
      )ciHL mice. 

PMID- 25862098
TI  - Excitation of skeletal muscle is a self-limiting process, due to run-down of Na+,
      K+ gradients, recoverable by stimulation of the Na+, K+ pumps.
AB  - The general working hypothesis of this study was that muscle fatigue and force
      recovery depend on passive and active fluxes of Na(+) and K(+). This is tested by
      examining the time-course of excitation-induced fluxes of Na(+) and K(+) during 5
      300 sec of 10-60 Hz continuous electrical stimulation in rat extensor digitorum
      longus (EDL) muscles in vitro and in vivo using (22)Na and flame photometric
      determination of Na(+) and K(+). 60 sec of 60 Hz stimulation rapidly increases
      (22)Na influx, during the initial phase (0-15 sec) by 0.53 MUmol(sec)(-1)(g wet
      wt.)(-1), sixfold faster than in the later phase (15-60 sec). These values agree
      with flame photometric measurements of Na(+) content. The progressive reduction
      in the rate of excitation-induced Na(+) uptake is likely to reflect gradual loss
      of excitability due to accumulation of K(+) in the extracellular space and t
      tubules leading to depolarization. This is in keeping with the concomitant
      progressive loss of contractile force previously demonstrated. During electrical
      stimulation rat muscles rapidly reach high rates of active Na(+), K(+)-transport
      (in EDL muscles a sevenfold increase and in soleus muscles a 22-fold increase),
      allowing efficient and selective compensation for the large excitation-induced
      passive Na(+), K(+)-fluxes demonstrated over the latest decades. The excitation
      induced changes in passive fluxes of Na(+) and K(+) are both clearly larger than
      previously observed. The excitation-induced reduction in [Na(+)]o contributes
      considerably to the inhibitory effect of elevated [K(+)]o. In conclusion,
      excitation-induced passive and active Na(+) and K(+) fluxes are important causes
      of muscle fatigue and force recovery, respectively. 

PMID- 25862099
TI  - Mean square delay dependent-probability-distribution stability analysis of
      neutral type stochastic neural networks.
AB  - The aim of this manuscript is to investigate the mean square delay dependent
      probability-distribution stability analysis of neutral type stochastic neural
      networks with time-delays. The time-delays are assumed to be interval time
      varying and randomly occurring. Based on the new Lyapunov-Krasovskii functional
      and stochastic analysis approach, a novel sufficient condition is obtained in the
      form of linear matrix inequality such that the delayed stochastic neural networks
      are globally robustly asymptotically stable in the mean-square sense for all
      admissible uncertainties. Finally, the derived theoretical results are validated
      through numerical examples in which maximum allowable upper bounds are calculated
      for different lower bounds of time-delay. 

PMID- 25862100
TI  - Increased Incidence and Severity of Postoperative Radiographic Hallux Valgus
      Interphalangeus With Surgical Correction of Hallux Valgus.
AB  - BACKGROUND: A previous study has shown an increased radiographic prevalence and
      severity of hallux valgus interphalangeus (HVIP) after surgical correction of
      hallux valgus (HV) due to correction of pronation deformity. The purpose of this
      study was to evaluate the change in pre- and postoperative HVIP deformity with
      correction of HV with multiple radiographic parameters. METHODS: A retrospective
      chart review identified all bunion surgeries performed at a single center from
      July 1, 2009, to September 30, 2012. Exclusion criteria included prior bony
      surgery to the first ray, inadequate films, nonadult bunion, Akin osteotomy, or
      surgical treatment other than bunion correction. Pre- and postoperative films
      were reviewed for 2 HV angular measurements and 5 HVIP measurements, which were
      compared. The angles measured were hallux valgus angle (HVA), first
      intermetatarsal angle (IMA), hallux interphalangeus angle (HIA), distal
      metatarsal articular angle (DMAA), proximal phalangeal articular angle (PPAA),
      proximal to distal phalangeal articular angle (PDPAA), and total distal deformity
      (TDD). Prevalence of HVIP was analyzed in pre- and postoperative radiographs. A 1
      sided Student t test was used to compare continuous data, and a chi-square test
      was used to compare categorical data. Ninety-two feet in 82 patients were
      eligible. RESULTS: The average preoperative HV improved with surgery.
      Preoperative HVA improved from 27 to 11 degrees (P < .001). Preoperative IMA
      improved from 13.6 to 6.1 degrees (P < .001). HVIP worsened after surgery.
      Preoperative HIA increased from 7.2 to 13.2 degrees (P < .001). DMAA worsened
      from 7.3 to 9.2 degrees (P = .001). PPAA worsened from 3.2 to 6.2 degrees. PDPAA
      worsened from 6.7 to 8.2 degrees (P < .001). The TDD increased from 14.6 to 17.9
      degrees (P < .001). The prevalence of HVIP pre- and postoperatively as defined by
      HIA increased from 26% to 79% (P < .001) and by PPAA from 12% to 46% (P < .001).
      CONCLUSION: Initial assessment of preoperative radiographs underestimated HVIP.
      Postoperative correction of the deformity revealed HVIP that was not obvious
      preoperatively. LEVEL OF EVIDENCE: Level III, retrospective comparative series.

PMID- 25862101
TI  - Effect of Age on Outcomes in Total Ankle Arthroplasty.
AB  - BACKGROUND: Little is known about the efficacy and durability of total ankle
      arthroplasty (TAA) in younger patients. The purpose of this study was to
      determine the effect of age on the clinical, radiographic, and patient-reported
      outcomes of patients with end-stage ankle arthritis treated with TAA using modern
      prostheses. METHODS: Patients who underwent primary TAA from June 2007 to July
      2011 were prospectively enrolled in the study. Three hundred and ninety-five
      consecutive patients were reviewed with a mean follow-up of 3.5 years (range, 2
      5.4 years). Patients were divided into 3 groups based on age at the time of
      surgery (<55, 55-70, and >70 years). Patient-reported outcome scores, physical
      performance scores, and weight-bearing radiographs were used to assess patients
      preoperatively and at yearly postoperative office visits. Revision was defined as
      failure of either the tibial or talar components requiring removal of the
      metallic implants. A repeated-measures analysis of variance with post hoc testing
      and the Pearson chi-square test were used to assess differences between the 3
      groups. Statistical significance was set at an alpha level of .05. RESULTS:
      Patients under the age of 55 had a greater improvement in Short-Form 36 (SF-36)
      Vitality (P = .026) and American Orthopaedic Foot & Ankle Society (AOFAS)
      Function scores (P < .001) compared with patients over the age of 70 at most
      recent follow-up. There were no differences in the Visual Analog Scale (VAS) pain
      score or the physical performance outcomes between the age groups. The incidence
      of wound complications, need for reoperation, and revision were not different
      between groups. CONCLUSIONS: Outcomes of TAA in younger patients were similar to
      outcomes in older patients at early follow-up. This study establishes a cohort of
      patients that will be followed to determine the effect of age on the long-term
      outcomes of TAA with an emphasis on the need for reoperation and revision. LEVEL
      OF EVIDENCE: Level II, prospective comparative study.

PMID- 25862102
TI  - Survival Analysis of the Single- and Double-Coated STAR Ankle up to 20 Years:
      Long-Term Follow-up of 324 Cases From the Swedish Ankle Registry.
AB  - BACKGROUND: The Scandinavian Total Ankle Replacement (STAR) has been used widely
      in Europe and more recently in the United States. We studied the results of the
      single-coated and the double-coated STAR with long-term follow-up. METHODS: All
      STARs (n = 324) used in Sweden (first implanted in 1993) were included.
      Prosthetic survival was estimated according to Kaplan-Meier. RESULTS: The 14-year
      survival of the single-coated STAR was 0.47 (95% confidence interval [CI], 0.38
      0.66), and the 12-year survival of the double-coated STAR was 0.64 (95% CI, 0.57
      0.71). Women younger than 60 years with osteoarthritis had a statistically
      significantly higher risk of revision than men and than patients with other
      diagnoses. CONCLUSION: The long-term results of the STAR prosthesis are not
      encouraging. The results seem to deteriorate by time. LEVEL OF EVIDENCE: Level
      IV, retrospective case series.

PMID- 25862103
TI  - Trends in pediatric firearm-related injuries over the past 10 years at an urban
      pediatric hospital.
AB  - PURPOSE: Firearm injuries are the second most common cause of trauma deaths in
      American children. We reviewed gunshot wounds treated at an urban children's
      hospital to determine the most likely time for injuries to occur over 10 years.
      METHODS: A retrospective chart review was completed for patients with a firearm
      injury from January 2003 to December 2012. Patients were excluded if over 17
      years or readmitted. Demographics, injury circumstances, interventions, and
      outcomes were reviewed for 289 patients. Chi square and ANOVA analyses were
      completed. Alpha was chosen as p<0.05. RESULTS: Mean age was 12 years, 74% were
      male and 80% African American. Unintentional injuries occurred in 26% and
      violence related in 72%. The most common months of injury were August and June,
      the least common November and October. Unintentional injuries were more likely to
      occur during the day and violence related injuries were more likely at night
      (p=0.01). The incidence was lowest 2008-2010 and highest in 2006 and 2011.
      Mortality was 3.5%. CONCLUSIONS: We noted an increasing incidence of pediatric
      firearm related injuries in the last two years of the study with over half
      requiring operative intervention. Most injuries were violence related and
      occurred in a large city during summer months.

PMID- 25862104
TI  - A novel duplex real time quantitative reverse transcription polymerase chain
      reaction for rubella virus with armored RNA as a noncompetitive internal positive
      control.
AB  - The objective of this study was to build and apply a duplex real time
      quantitative reverse transcription-polymerase chain reaction (RT-PCR) for rubella
      virus. Firstly, a 60-bp-long armored RV RNA was constructed in the laboratory.
      Secondly, a duplex real time RT-PCR assay was established. Thirdly, the 60-bp
      long armored RV RNA was used as an internal positive control (IPC) for the duplex
      real time RT-PCR. And finally the duplex real time RT-PCR assay was applied to
      detect RV RNA in clinical specimens. The in-house assay has a high amplification
      efficiency (0.99), a high analytical sensitivity (200 copies/mL), and a good
      reproducibility. The diagnostic specificity and sensitivity of the in-house assay
      were both 100%, due to the monitoring of the armored RV RNA IPC. Therefore, the
      in-house duplex real time quantitative RT-PCR assay is a specific, sensitive,
      reproducible and accurate assay for quantitation of RV RNA in clinical specimens.
      And noncompetitive armored RV RNA IPC can monitor RT-PCR inhibition and prevent
      false-negative and inaccurate results in the real time detection system.

PMID- 25862105
TI  - Localization in the Interpeduncular Cistern as Risk Factors for the
      Thalamoperforators' Ischemia, Poor Outcome, and Oculomotor Nerve Palsy in
      Patients with Complex Unruptured Basilar Apex Aneurysm Treated with Neck
      Clipping.
AB  - OBJECTIVE: We aimed to evaluate the relationship between aneurysm morphology,
      thalamoperforators' ischemia, outcome, and oculomotor nerve palsy (ONP) that
      continued during the follow-up period in 23 patients with complex unruptured
      basilar apex aneurysms (BAAs) treated with clipping. METHODS: Aneurysm morphology
      included the size, distance of neck from the posterior clinoid process, dome
      projection, and localization in the interpeduncular cistern (LIC). BAAs with neck
      >4 mm, posterior projection, retro/subsellar, and dome-to-neck ratios <1.2 were
      considered as complex. The poor outcome was defined as modified Rankin Scale
      (mRS) 2-6 at the 12 months' follow-up examination. RESULTS: All patients were
      treated by anterior temporal approach. Size (P < 0.0001) and LIC (P < 0.0001)
      were related to thalamoperforators' ischemia (n = 3, 13%). Size (P = 0.0010),
      dividing-posterior communicating artery (P = 0.0050), thalamoperforator's
      ischemia (P = 0.034), and LIC (P < 0.0001) were related to poor outcome (mRS 2: n
      = 3, 13%). The mean follow-up period was 368 +/- 52 days. No patients developed a
      bleed and showed evidence of any residual or recurrent aneurysm during follow-up.
      Postoperative ONP occurred in 15 patients (65%) and all were partial. During
      follow-up, full recovery of the ONP was seen in 13 patients (57%), and it
      continued in 2 (8.7%). Size (P = 0.010) and posterior projection (P = 0.043) and
      LIC (P = 0.0050) were related to continued ONP. CONCLUSIONS: The present study
      suggested that unruptured BAA patients with LIC should be meticulously treated in
      case of performing clipping because it was related to thalamoperforators'
      ischemia, poor outcome, and continued ONP.

PMID- 25862106
TI  - Quantification of Forces During a Neurosurgical Procedure: A Pilot Study.
AB  - OBJECTIVE: Knowledge of tool-tissue interaction is mostly taught and learned in a
      qualitative manner because a means to quantify the technical aspects of
      neurosurgery is currently lacking. Neurosurgeons typically require years of hands
      on experience, together with multiple initial trial and error, to master the
      optimal force needed during the performance of neurosurgical tasks. The aim of
      this pilot study was to develop a novel force-sensing bipolar forceps for
      neurosurgery and obtain preliminary data on specific tasks performed on cadaveric
      brains. METHODS: A novel force-sensing bipolar forceps capable of measuring
      coagulation and dissection forces was designed and developed by installing strain
      gauges along the length of the bipolar forceps prongs. The forceps was used in 3
      cadaveric brain experiments and forces applied by an experienced neurosurgeon for
      10 surgical tasks across the 3 experiments were quantified. RESULTS: Maximal peak
      (effective) forces of 1.35 N and 1.16 N were observed for dissection (opening)
      and coagulation (closing) tasks, respectively. More than 70% of forces applied
      during the neurosurgical tasks were less than 0.3 N. Mean peak forces ranged
      between 0.10 N and 0.41 N for coagulation of scalp vessels and pia-arachnoid,
      respectively, and varied from 0.16 N for dissection of small cortical vessel to
      0.65 N for dissection of the optic chiasm. CONCLUSIONS: The force-sensing bipolar
      forceps were able to successfully measure and record real-time tool-tissue
      interaction throughout the 3 experiments. This pilot study serves as a first step
      toward quantification of tool-tissue interaction forces in neurosurgery for
      training and improvement of instrument handling skills.

PMID- 25862107
TI  - Intradural Extramedullary Ependymoma with Leptomeningeal Dissemination: The First
      Case Report in a Child and Literature Review.
AB  - BACKGROUND: Primary intradural extramedullary ependymomas are very rare tumors
      and have never been described in children. CASE DESCRIPTION: We report on an 11
      year-old girl presenting with a 1-month history of neck pain, left arm weakness,
      paresthesia in the fingers of the left hand and gait disturbances. Magnetic
      resonance imaging on admission revealed an intradural extramedullary cystic
      lesion at the cervical level with craniospinal leptomeningeal nodules causing
      mild hydrocephalus. The multicystic lesion was surgically removed and
      neuropathologic examination revealed a World Health Organization grade II
      ependymoma. The patient underwent adjuvant radiotherapy with progressive
      reduction of the metastatic nodules. At her 2-year follow-up, the patient was
      symptom free with no evidence of recurrence on magnetic resonance imaging.
      CONCLUSIONS: Although a rare entity, intradural extramedullary ependymomas should
      be included in the differential diagnosis of intradural extramedullary lesions in
      children. Surgical treatment seems to play a pivotal role in the prognosis of
      these rare tumors, with a possible role for adjunctive radiotherapy in the case
      of recurrence, anaplastic transformation, and metastasis.

PMID- 25862108
TI  - Stereotactic-Guided Evacuation of Spontaneous Supratentorial Intracerebral
      Hemorrhage: Systematic Review and Meta-Analysis.
AB  - BACKGROUND: Spontaneous intracerebral hemorrhage (SICH) has a high morbidity and
      mortality and places a huge significant economic burden on health care and social
      services. The role of surgery is still controversial as evidenced by wide
      variation internationally in management of SICH. Traditional surgery for SICH
      involved open craniotomy with hematoma evacuation. Using available evidence, this
      article assesses the efficacy of stereotactic-guided evacuation compared with
      medical treatment. METHODS: A systematic review was performed comparing
      stereotactic-guided evacuation of SICH with conservative medical management.
      Eligible studies were identified using a text word search of an electronic
      journal database for randomized controlled trials. Extracted data outcomes were
      subjected to meta-analysis with a forest plot. Quality was assessed using
      Cochrane risk of bias analysis tools. RESULTS: There were 5 studies with 740
      patients. There was a nonsignificant reduction in odds ratio (OR) for death at
      the end of the follow-up period (OR = 0.74, 95% confidence interval = 0.45-1.21)
      with no significant heterogeneity. Nonsignificant benefits were observed for
      dependent survival (OR = 2.14, 95% confidence interval = 0.31-0.58). In the
      subgroup analysis, stereotactic evacuation showed improved outcomes in patients
      with hematoma volume <50 mL. In this review, the effectiveness of stereotactic
      evacuation plus subsequent thrombolysis was insignificant (OR = 1.34, 95%
      confidence interval = 0.57-3.12). CONCLUSIONS: The outcome of patients who had
      stereotactic-guided evacuation of SICH was not better compared with patients who
      received medical treatment; however, there was a trend toward better quality of
      survival and chance of survival in the stereotactic-guided evacuation group. This
      study identified areas for further research.

PMID- 25862109
TI  - Preoperative Angiography of Middle Cerebral Artery Bifurcation Aneurysms.

PMID- 25862110
TI  - Surgical Management of Giant Basilar Tip Aneurysm Associated with Moyamoya
      Disease: A Case Report and Literature Review.
AB  - BACKGROUND: We report the efficacy and safety of surgical treatment with the
      orbitozygomatic transsylvian approach and the rarity of accompanying subarachnoid
      hemorrhage, Terson syndrome, and ruptured giant basilar tip aneurysm in a patient
      affected by moyamoya disease with a good outcome. METHODS: A 40-year-old man with
      a history of exertional headache from childhood and hypertension diagnosed 5
      years previously was referred to us with the presenting symptom of headache.
      After 1 day, he developed left hemiplegia, decreased level of consciousness, and
      blindness in the left eye. Imaging studies revealed a subarachnoid hemorrhage and
      giant basilar tip aneurysm. He underwent surgical clipping of the aneurysm using
      the orbitozygomatic transsylvian approach. RESULTS: With obvious improvement in
      strength and consciousness, the patient was discharged. Early diagnosis and
      treatment of the other possible complications of moyamoya disease were
      recommended. CONCLUSIONS: The rarity and different manifestations of moyamoya
      disease require individualized decision making with regard to cerebrovascular
      complications. Individualized decision making and the cooperation of medical
      teams are the mainstays of treatment.

PMID- 25862111
TI  - Primary Meningeal Melanocytoma in the Left Temporal Lobe Associated with Nevus
      Ota: a Case Report and Review of the Literature.
AB  - BACKGROUND: Primary melanocytic neoplasms of the central nervous system are rare
      lesions arising from melanocytes of the leptomeninge that are found at highest
      density underneath the brain stem and along the upper cervical spinal cord. Thus
      most reported cases of meningeal melanocytomas are located in the posterior fossa
      and the spinal cord, and presentation of a supratentorial tumor is rare. METHODS:
      A 19-year-old man presented with a headache and seizure at our department.
      Neurological examinations were otherwise normal. On physical examination he had
      asymptomatic, bluish, speckled, and well-demarcated hyperpigmented macules on the
      left midface extraorally. A left temporal space-occupying lesion was seen on
      magnetic resonance imaging. The mass was hyperintense on T1-weighted images and
      isointense on T2-weighted images. Enhancement was shown on contrast-enhanced
      magnetic resonance imaging (MRI). The preoperative diagnosis was meningioma.
      RESULT: Gross complete resection was performed. Pathological studies led to the
      diagnosis of meningeal melanocytoma World Health Organization (WHO) grade I. The
      patient received oncologic consultation. Because total resection of the tumor was
      achieved and its histopathologic grade was benign (WHO grade I), radiotherapy was
      not advised for the patient and he followed up every 6 months. No tumor was seen
      on follow-up MRI one year after surgery. CONCLUSION: Presentation of meningeal
      melanocytoma in the supratentorial compartment is rare, and its combination with
      nevus Ota has been reported in very few cases. Although this lesion is benign, it
      might behave aggressively. Complete surgical resection of the lesion is the
      preferred therapeutic option.

PMID- 25862112
TI  - Surgeon Perspective on Complications After Surgery for Cervical Myelopathy.

PMID- 25862113
TI  - Training in Brain Retraction Using a Self-Made Three-Dimensional Model.
AB  - A hollow brain model was created using soft urethane. A tube passing through the
      hollow was attached for use as a water inlet and manometer. Water sufficient in
      quantity to realize the intended initial pressure was infused through the tube.
      The brain model was retracted with a brain spatula and the surgical corridor was
      opened. By measuring local force with a sensor set on the brain spatula, the
      model could be used for training in brain retraction. At the same time, the water
      column of the manometer was measured and the relationship with the force of the
      brain spatula was investigated. A positive correlation between the water column
      and local force was confirmed. This indicated that it was possible to use this
      model without a force sensor for the same training using water column
      measurements. 

PMID- 25862114
TI  - Ghost Tumors of the Central Nervous System: Definition, Clinical Implications,
      and Proposal of Classification.
AB  - BACKGROUND: A ghost tumor (GhT) is a space-occupying lesion with radiologic
      features consistent with the diagnosis of tumor that on further investigation is
      revealed not to be a tumor, although definitions in the literature are
      inconsistent, and the incidence of GhT remains undefined. METHODS: A review of
      the pertinent literature was performed to identify pediatric patients in whom a
      misleading initial diagnosis of space-occupying lesion was described. Analysis of
      the differentiating features of the final diagnosis and related clinical and
      radiologic issues was performed. RESULTS: GhT may be categorized as follows: GhT
      I, lesions spontaneously disappearing during follow-up, also known as "vanishing
      tumors"; GhT II, nonneoplastic space-occupying lesions showing a tumor
      appearance, also known as "tumor-like lesions"; GhT III, anatomic variants of
      normal structures mimicking a tumor, also defined as "false tumors." The most
      deceptive conditions and critical points in the differential diagnosis of these
      cases were discussed. CONCLUSIONS: GhT is an entity with significant implications
      in regard to treatment and outcome. In this context, the integration of clinical
      and radiologic clues is crucial for a careful differential diagnosis and a
      consistent diagnostic approach, which is necessary for adequate decision making
      regarding management. A thorough radiologic work-up is mandatory. Atypical
      radiologic images should raise a high level of suspicion, including incidental
      lesions, which are encountered with increasing frequency in daily practice as a
      result of greater access to radiologic examinations, increasing sensitivity of
      imaging, and the impact of defensive medicine. A wait-and-see policy should be
      considered whenever indicated.

PMID- 25862115
TI  - Induction of Fear by Intraoperative Stimulation During Awake Craniotomy: Case
      Presentation and Systematic Review of the Literature.
AB  - PURPOSE: A case is presented and a systematic review of the literature is
      provided to update our current knowledge of induction of fear by cortical
      stimulation. METHODS: We present a case of refractory epilepsy associated with a
      lesion where fear could be induced by intraoperative electrical stimulation of
      the posterior inner part of the superior temporal gyrus. We performed a
      systematic review of the literature using PubMed with the key words "epilepsy AND
      emotion", "cortical stimulation AND emotion," and "human brain stimulation AND
      behavior". RESULTS: Intraoperative cortical stimulation of the inner part of the
      posterior superior temporal gyrus reliably induced fear and progressive screaming
      behavior. Stimulation through subdural grid electrodes did not induce this
      phenomenon. A systematic review of the literature identified fear induction by
      stimulation of different widespread cortical areas including the temporal pole,
      the insula, and the anterior cingulate cortex. The posterior part of the superior
      temporal gyrus has so far not been associated with fear induction after
      electrical stimulation. CONCLUSION: Although our observation suggests that this
      area of the brain could be part of a network involved in the elicitation of fear,
      dysfunction of this network induced by epilepsy could also explain the observed
      phenomenon. Electrophysiologic and imaging studies must be conducted to improve
      our understanding of the cortical networks forming the neuroanatomical substrate
      of higher brain functions and experiences such as fear.

PMID- 25862116
TI  - Melatonin improves sleep in children with epilepsy: a randomized, double-blind,
      crossover study.
AB  - OBJECTIVE: Insomnia, especially maintenance insomnia, is widely prevalent in
      epilepsy. Although melatonin is commonly used, limited data address its efficacy.
      We performed a randomized, double-blind, placebo-controlled, crossover study to
      identify the effects of melatonin on sleep and seizure control in children with
      epilepsy. METHODS: Eleven prepubertal, developmentally normal children aged 6-11
      years with epilepsy were randomized by a software algorithm to receive placebo or
      a 9-mg sustained release (SR) melatonin formulation for four weeks, followed by a
      one-week washout and a four-week crossover condition. The pharmacy performed
      blinding; patients, parents, and study staff other than a statistician were
      blinded. The primary outcomes were sleep onset latency and wakefulness after
      sleep onset (WASO) measured on polysomnography. The secondary outcomes included
      seizure frequency, epileptiform spike density per hour of sleep on
      electroencephalogram (EEG), and reaction time (RT) measures on psychomotor
      vigilance task (PVT). Statistical tests appropriate for crossover designs were
      used for the analysis. RESULTS: Data were analyzed from 10 subjects who completed
      the study. Melatonin decreased sleep latency (mean difference, MD, of 11.4 min
      and p = 0.02) and WASO (MD of 22 min and p = 0.04) as compared to placebo. No
      worsening of spike density or seizure frequency was seen. Additionally, slow-wave
      sleep duration and rapid eye movement (REM) latency were increased with melatonin
      and REM sleep duration was decreased. These changes were statistically
      significant. Worsening of headache was noted in one subject with migraine on
      melatonin. CONCLUSION: SR melatonin resulted in statistically significant
      decreases in sleep latency and WASO. No clear effects on seizures were observed,
      but the study was too small to allow any conclusions to be drawn in this regard.

PMID- 25862117
TI  - Continuous positive airway pressure treatment associated with face injury during
      rapid eye movement behavior disorder.

PMID- 25862118
TI  - Impact of obesity on cognitive outcome in children with sleep-disordered
      breathing.
AB  - OBJECTIVES: The objective of this study was to evaluate the impact of obesity on
      cognitive impairment, in children with obstructive sleep apnoea (OSA), children
      with OSA and obesity, and in normal controls. METHODS: Thirty-six children with
      OSA (group 1), 38 children with OSA and obesity (group 2) and 58 normal controls
      (group 3) were studied. The Total intelligence quotient (T-IQ), Verbal IQ (V-IQ)
      and the Performance IQ (P-IQ) scores were obtained using the Wechsler
      Intelligence Scale for Children - Third Edition Revised. All participants'
      parents filled out the questionnaire containing the attention deficit and
      hyperactive disorder rating scale to investigate symptoms of hyperactivity and
      attention deficit. Obese and non-obese children with sleep-disordered breathing
      (SDB) underwent polysomnography. RESULTS: T-QI and P-QI scores were significantly
      lower in group 2 with higher performance impairment at the subtest compared to
      other groups. In obese children, V-IQ was significantly correlated with age of
      onset (r = 0.335, p = 0.05) and duration of SDB (r = -0.362, p = 0.02), while P
      IQ and T-IQ were correlated with body mass index (BMI) percentile (r = -0.341, p
      = 0.03) and respiratory disturbance index (RDI) (r = -0.321, p = 0.05),
      respectively. RDI and BMI negatively influenced T-IQ in obese children with OSA.
      No correlation was found between sleep parameters and IQ scores or subtest scores
      in all groups. CONCLUSIONS: Obese children with OSA showed higher cognitive
      impairment. Obesity has an additive and synergic action with that exerted by OSA,
      speeding up the onset of complications.

PMID- 25862119
TI  - Nocturia is an independent predictive factor of prevalent hypertension in
      obstructive sleep apnea patients.
AB  - OBJECTIVE: The aim of this study was to determine whether nocturia is an
      independent predictor for prevalent hypertension in obstructive sleep apnea
      (OSA). METHODS: We analyzed data from a national prospective clinical cohort of
      OSA patients participating in the French national prospective registry.
      Anthropometric data, comorbidities, OSA severity, and number of voids/night were
      included in multivariate analyses to determine the independent variables
      associated with prevalent hypertension. RESULTS: A total of 22,674 OSA patients
      were included, of which 11,332 were hypertensive. The prevalence of hypertension
      among OSA patients was about 1.3 times higher in patients suffering from nocturia
      at 61.45% versus 46.52% in hypertensive and non-hypertensive OSA patients (p
      <0.001). There was a significant positive relationship between hypertension and
      the severity of nocturia beyond two voids/night: two voids/night versus none:
      odds ratio (OR) = 1.270 (95% confidence interval (CI) = 1.175; 1.372), three
      voids/night versus none: OR = 1.422 (95% CI = 1.293; 1.565), and four voids/night
      versus none: OR = 1.575 (95% CI = 1.394; 1.781). The strength of the association
      was enhanced in patients over 64 years of age. CONCLUSIONS: Nocturia is a strong
      independent predictor of prevalent hypertension in OSA. This association
      exhibited a "dose-response" relationship beyond two voids/night. The resolution
      of nocturia after continuous positive airway pressure (CPAP) treatment might be
      an important outcome to consider for the response of hypertension to CPAP.

PMID- 25862121
TI  - Characteristics of Men Undergoing Testosterone Replacement Therapy and Adherence
      to Follow-up Recommendations in Metropolitan Multicenter Health Care System.
AB  - OBJECTIVE: To identify the frequencies of treatment and recommended laboratory
      follow-up for men with low serum testosterone levels. METHODS: The Electronic
      Data Warehouse was queried to identify men of ages 18-85 years, who obtained a
      testing for serum total testosterone level from 2009 to 2012. The frequency of
      testosterone replacement therapy (TRT), patient demographics, and clinical
      characteristics were collected. The frequency of follow-up with serum total
      testosterone and complete blood count levels was documented. RESULTS: Among 9176
      men who underwent testing for low testosterone levels, 3320 (36%) of them were
      hypogonadal with a mean serum total testosterone level of 194.3 +/- 64.9 ng/dL.
      Of them, 17.7% men were treated with TRTs. The treatment frequency significantly
      increased from 8.3% in 2009 to 24% in 2012. A total of 4.8% of men of
      reproductive ages (age, 18-35 years) were placed on TRTs. Within 180 days of
      initial testing, only 40% of treated men received follow-up with liver function
      tests and/or complete blood count, and only 49% had a follow-up serum
      testosterone level. CONCLUSION: Although the frequency of TRT is increasing, only
      a small percentage of hypogonadal men are actively undergoing treatment. A
      significant proportion of men of reproductive age are being treated with
      significant impacts on potential fertility. Less than half of the patients
      treated are being monitored appropriately after testosterone replacement. This
      highlights the importance of further education for providers prescribing
      testosterone replacement.

PMID- 25862120
TI  - Sleep duration associated with body mass index among Chinese adults.
AB  - OBJECTIVE: The objective of this study was to investigate the relationship
      between sleep duration and obesity among Chinese adults. METHODS: A community
      based cross-sectional study was conducted among Chinese adults in 2008. In total,
      3225 participants were selected by a multistage cluster sampling method. Self
      reported sleep duration was measured by a standardized questionnaire. Logistic
      regression models were used to estimate the odds ratios (ORs) (95% confidence
      intervals, CIs) of obesity with sleep duration, separated by gender, and adjusted
      for age, education, occupation, marriage, smoking, drinking, body pain, and
      health status. RESULTS: The mean sleep duration was 7.8 h. Among the 2962
      participants, 7.2% had short sleep duration (<=6 h/day). There were 171 obese
      participants (5.7%) in this population. After adjustment for age, short sleep
      duration (<6 h) was significantly associated with obesity among men (OR: 2.15;
      95% CI: 1.193.90), but not among women; additional adjustment for potential
      confounders did not attenuate the association among men. Increasing sleep
      duration (a continuous variable) was significantly and negatively associated with
      obesity in women after adjustment for education level, occupation, marital
      status, smoking, drinking, body pain, and health status. The adjusted OR per-hour
      increase in sleep duration was 0.74 (0.56-0.97) for obesity, suggesting that for
      a 1-h increase in sleep duration among women, obesity risk decreased by 26%.
      CONCLUSION: Short sleep duration was associated with increasing obesity in
      Chinese men, and sleep duration was associated with obesity in Chinese women,
      although the underlying mechanism is unclear. This possible gender difference
      warrants further studies.

PMID- 25862122
TI  - In vitro evaluation of glutathione peroxidase (GPx)-like activity and antioxidant
      properties of an organoselenium compound.
AB  - The amine based diselenide, (Z)-N-(4-methylbenzylidene)-1-(2-((2-(1-((E)-4-methyl
      benzylideneamino)ethyl)phenyl)diselanyl)phenyl)ethanamine ethyl)phenyl)
      diselanyl) phenyl) ethylimino) methyl)phenol (Compound A) an organoselenium
      compound that can mimic endogenous antioxidant enzymes, such as glutathione
      peroxidase (GPx), and diphenyl diselenide (PhSe)2 were tested against lipid
      peroxidation induced by sodium nitroprusside (SNP) and Fe(II) in rat brain,
      interaction with 1,1-diphenyl-2-picrylhydrazyl stable free radical (DPPH) and
      glutathione peroxidase (GPx) like antioxidant activities with H2O2 or tBuOOH as
      substrates and with PhSH as thiol co-substrates as well as their ability to
      oxidize thiols were evaluated. From this study, we concluded that Compound A
      catalyze the reduction of H2O2 with thiol was ~2-fold more active than (PhSe)2)
      in both tBuOOH and H2O2 systems when PhSH was used as a substrate. (PhSe)2
      exhibited an increased ability to oxidize thiols while Compound A was not a good
      substrate for the oxidation of thiol used namely DTT and Cystine and showed DPPH
      radical-scavenging activity, while (PhSe)2 did not present radical scavenging
      activity. Compound A (amine based diselenide) presented better antioxidant
      profiles than (PhSe)2 against lipid peroxidation. The results clear showed that
      nitrogen atom in the Compound A can have a profound effect on their
      pharmacological properties. 

PMID- 25862123
TI  - Polarized location of SLC and ABC drug transporters in monolayer-cultured human
      hepatocytes.
AB  - Human hepatocytes cultured in a monolayer configuration represent a well
      established in vitro model in liver toxicology, notably used in drug transporter
      studies. Polarized status of drug transporters, i.e., their coordinated location
      at sinusoidal or canalicular membranes, remains however incompletely documented
      in these cultured hepatocytes. The present study was therefore designed to
      analyze transporter expression and location in such cells. Most of drug
      transporters were first shown to be present at notable mRNA levels in monolayer
      cultured human hepatocytes. Cultured human hepatocytes, which morphologically
      exhibited bile canaliculi-like structures, were next demonstrated, through
      immunofluorescence staining, to express the influx transporters organic anion
      transporting polypeptide (OATP) 1B1, OATP2B1 and organic cation transporter (OCT)
      1 and the efflux transporter multidrug resistance-associated protein (MRP) 3 at
      their sinusoidal pole. In addition, the efflux transporters P-glycoprotein and
      MRP2 were detected at the canalicular pole of monolayer-cultured human
      hepatocytes. Moreover, canalicular secretion of reference substrates for the
      efflux transporters bile salt export pump, MRP2 and P-glycoprotein as well as
      sinusoidal drug transporter activities were observed. This polarized and
      functional expression of drug transporters in monolayer-cultured human
      hepatocytes highlights the interest of using this human in vitro cell model in
      xenobiotic transport studies. 

PMID- 25862124
TI  - Toxic mechanisms of copper oxide nanoparticles in epithelial kidney cells.
AB  - CuO NPs have previously been reported as toxic to a range of cell cultures
      including kidney epithelial cells from the frog, Xenopus laevis (A6). Here we
      examine the molecular mechanisms affecting toxicity of Cu in different forms and
      particle sizes. A6 cells were exposed to ionic Cu (Cu2+) or CuO particles of
      three different sizes: CuO NPs of 6 nm (NP6), larger Poly-dispersed CuO NPs of
      <100 nm (Poly) and CuO Micro particles of <5 MUm (Micro), at 200 MUM, equal to
      12.7 mg Cu/L. Poly was significantly more toxic than NP6, Micro and Cu2+ to A6
      cells, causing DNA damage, decreased cell viability and levels of reduced
      glutathione (GSH) and eventually cell death. We show that ROS (Reactive Oxygen
      Species) generation plays a key role and occurs early in Poly toxicity as Poly
      induced DNA damage and cell death could be mitigated by the antioxidant NAC (N
      acetyl-cysteine). Here we propose a model of the sequence of events explaining
      Poly toxicity. Briefly, the events include: cellular uptake, most likely via
      endocytosis, production of ROS, which cause DNA damage that activates a signaling
      pathway which eventually leads to cell death, mainly via apoptosis.

PMID- 25862125
TI  - [Surgical reconstruction procedures for Charcot foot].

PMID- 25862126
TI  - [Treatment of hindfoot instability in Charcot foot using a hybrid technique of
      internal and external fixation].
AB  - OBJECTIVE: The main problem of patients with Charcot foot is their inability to
      off-load. Therefore the risk of internal fixation failure is increased,
      especially in hindfoot instability (Sanders type IV) with osteonecrosis of the
      talus. Combination of internal and additional external fixation guarantees the
      reconstruction and improves surgical outcome. The main objective of this surgery
      is to obtain a resilient, plantigrade foot that is shoeable in custom-made
      orthopedic shoes. INDICATIONS: Charcot foot with instable collapse of the
      hindfoot with or without fragment dislocation, with or without (noninfected)
      ulceration not shoeable in custom-made orthopedic shoes. CONTRAINDICATIONS: Very
      poor general condition, non-reconstructible peripheral vascular disease, deep
      infection and defects in the region of surgery which makes amputation nescessary,
      and poor patient compliance. SURGICAL TECHNIQUE: Excision of the distal fibula
      and removal of the destroyed talus body using a lateral approach. Medial approach
      to remove the medial malleolus. Tibiocalcaneal fusion using screws for internal
      fixation. Fusion of the talus head to the anterior tibia. Ilizarov external
      fixateur to stabilize the internal fixation. POSTOPERATIVE MANAGEMENT: Off
      loading for 3 months, then CT scan to verify bony fusion and according to the
      findings stepwise weight-bearing in a cast or walker over 4-6 weeks. Then custom
      made orthopedic shoes with a high shaft and insoles for neuropathic patients and
      full weight-bearing. RESULTS: In a retrospective cohort study, 14 of 16 patients
      could be fitted in custom-made shoes after undergoing tibiocalcaneal fusion.
      During follow-up, 2 patients required below-knee amputation, 3 patients had
      stress fractures of the tibia, one related to a pin track infection. All patients
      had a bony fusion of calcaneus and tibia; 10 of 16 patients had fusion of
      midfoot/talus head and the distal tibia. The 10 patients who had an ulcer before
      surgery could be healed. In 1 patient, a heel ulcer developed due to talipes
      calcaneus.

PMID- 25862127
TI  - [Tibiotalocalcaneal corrective arthrodesis in Charcot arthropathy of the ankle
      with a retrograde nail].
AB  - BACKGROUND: Involvement of the ankle joint in Charcot osteoarthropathy is most
      often associated with severe instability and fracture or collapse of the talus.
      Caused by malalignment, ulcerations over both malleoli are associated with
      increased risk of major amputation. OBJECTIVE: The goal of the operation is to
      realign the hind foot, gain a stable osteosynthesis, and prevent major
      amputation. INDICATIONS: Charcot osteoarthropathy of the ankle joint with
      instability, with or without soft tissue involvement, failure of the primary
      arthrodesis of the ankle or subtalar joint. CONTRAINDICATIONS: Acute
      osteitis/osteomyelitis, severe malalignment of the distal tibia, soft tissue
      infection close to the ankle joint. SURGICAL TECHNIQUE: Realignment of the hind
      foot, preparation of the joint surfaces using a transfibular approach. Bone
      grafting of the defects, stable osteosynthesis with an anatomically shaped
      retrograde locking nail. POSTOPERATIVE MANAGEMENT: Walker or cast for at least 12
      weeks, 6 weeks no weight bearing. Partial weight bearing starting from week 7. X
      ray control at 2, 6, and 12 weeks. After 12 weeks, walking in an ankle brace
      until fully consolidated.

PMID- 25862128
TI  - [Management of midfoot instability in Charcot foot with the ring fixator : Use of
      a hybrid technique with internal and external stabilization].
AB  - OBJECTIVE: Combination of external and internal fixation for improvement of
      stabilization in midfoot arthrodesis. INDICATIONS: Charcot foot of the midfoot
      with/without (infection-free) ulceration. CONTRAINDICATIONS: Severe
      anesthesiological risks in multimorbid patients; untreated symptomatic peripheral
      arterial occlusive disease; severe soft tissue infection and defect with the
      necessity of amputation. SURGICAL TECHNIQUE: Performing subtractive resection
      arthrodesis of the midfoot with locking plates and screws combined with an
      external ring fixator of the foot and lower leg. POSTOPERATIVE MANAGEMENT:
      Postoperative partial weight bearing with sole contact and walking frame for 3
      months. Then removal of external fixator, CT scan and based on the result, staged
      increasing of stress load with short-leg cast over a period of 4-6 weeks.
      Podomechanotherapy with full weight bearing. RESULTS: With this surgical
      procedure, sufficient stabilization with fully load bearing, plantigrade foot
      with podomechanotherapy with the help of a combined internal and external
      fixation is possible. Complications (pin-tract infection or dislocation) exist,
      but they can be controlled. High healing rate of ulceration was achieved by bony
      position correction and stabilization.

PMID- 25862129
TI  - [Corrective arthrodesis of midfoot Charcot neuroosteoarthropathy with internal
      fixation].
AB  - OBJECTIVE: The goal of treatment is a plantigrade, stable, ulcer-free foot which
      can be addressed with diabetes-adapted insoles and/or DNOAP shoes. INDICATIONS:
      Charcot foot of the midfoot with/without infection-free ulcers.
      CONTRAINDICATIONS: Inacceptable anesthesiological risk in polymorbidity. Severe
      anesthesiological risks in multimorbid patients; symptomatic peripheral arterial
      occlusive disease not suitable for reconstruction; infections PEDIS/IWGDF grade 3
      or 4, nonreconstructable osseous defects. SURGICAL TECHNIQUE: Corrective
      arthrodesis with segmental resection or bone grafting of the midfoot to achieve a
      plantigrade foot position. Plantar plate application or intramedullary (e.g.,
      midfoot fusion bolt) and extramedullary (preferably: angular stable locking
      plates) implant combinations to create the highest possible degree of primary
      stability of the medial and/or lateral foot columns (superconstruct). In case of
      higher degrees of instability, the hindfoot should also be included into the
      arthrodesis. POSTOPERATIVE MANAGEMENT: Partial weight-bearing (20 kg) with
      forearm crutches for 3-5 months postoperatively in special orthosis or total
      contact cast. Therapeutic shoes with diabetes-adapted insoles with full weight
      bearing. RESULTS: Using any of these stabilization variants, a plantigrade,
      stable, and long-lasting ulcer-free foot may be obtained that is suitable for
      custom-made footwear. The outcome does not depend on definite osseous healing of
      the arthrodesis and allows for the patient to have a self-determined lifestyle.
      The consecutive rate of amputation is low. COMPLICATIONS: High rate of surgical
      complications (e.g., infection, implant failure, non-union, loss of correction,
      reulceration), in particular, in cases of inadequate indication or insufficient
      primary stability.

PMID- 25862130
TI  - [Erratum to: Defect reconstruction in total knee arthroplasty with wedges and
      blocks].

PMID- 25862131
TI  - [Suturing and refixation of the medial collateral ligament in severe acute medial
      instability of the knee].
AB  - OBJECTIVE: Restoration of the medial stability after acute lesion of the medial
      collateral ligament (MCL) and of the posteromedial complex in case of a high
      grade instability of the MCL. Stabilization against valgus stress and prevention
      of an increased posterior drawer in case of a lesion of the posterior oblique
      ligament (POL). INDICATIONS: Acute high grade instability (grade 3) of the MCL.
      Rupture of the POL in combination with a rupture of the PCL and/or of the ACL.
      Multiligamentous injuries. Stener-like lesion of the tibial insertion of the MCL
      fibers with subluxation of the MCL superficial to the pes anserinus
      superficialis. CONTRAINDICATIONS: Local infection, poor soft tissue condition,
      severe soft tissue defects, intraligamentous injuries of the MCL (grade I-II
      instabilities). SURGICAL TECHNIQUE: The refixation of the MCL and the
      posteromedial complex has to respect anatomical situation. Femoral or tibial
      avulsions of the MCL can be reattached by the use of anchors at the anatomical
      insertion sites. Intraligamentous ruptures must be adapted. Additional framelike
      sutures may be used. The fixation and readaption of the MCL and the posteromedial
      complex can be combined with ACL and PCL procedures. POSTOPERATIVE MANAGEMENT:
      Use of a brace for 6 weeks to avoid valgus stress, partial weight bearing (10-20
      kg). Weeks 1-3: ROM 0-20-60 degrees  extension/flexion; weeks 4-6: ROM 0-10-90
      degrees  extension/flexion; after 7 weeks: free ROM. The postoperative protocol
      must be more restrictive in case of a combination of a MCL fixation and a PCL
      reconstruction (6 weeks immobilization in extension with posterior support,
      exercise only in prone position). RESULTS: Between 2010 and 2013, 34 cases of
      acute medial instability were treated. According to the injury pattern, some
      procedures were isolated MCL refixations, while others were combined procedures.
      While 25 patients showed a concomitant ACL injury, 13 patients had combined PCL
      and ACL injury. Postoperatively all medial instabilities had improved. Revision
      surgery was performed in 3 cases due to postoperative arthrofibrosis.

PMID- 25862133
TI  - An emerging role for immune regulatory subsets in chronic lymphocytic leukaemia.
AB  - The last few years has seen the burgeoning of a new category of therapeutics for
      cancer targeting immune regulatory pathways. Antibodies that block the PD-1/PD-L1
      interaction are perhaps the most prominent of these new anti-cancer therapies,
      but several other inhibitory receptor ligand interactions have also shown promise
      as targets in clinical trials, including CTLA-4/CD80 and Lag-3/MHC class II.
      Related to this is a rapidly improving knowledge of 'regulatory' lymphocyte
      lineages, including NKT cells, MAIT cells, B regulatory cells and others. These
      cells have potent cytokine responses that can influence the functioning of other
      immune cells and many researchers believe that they could be effective targets
      for therapies designed to enhance immune responses to cancer. This review will
      outline our current understanding of FOXP3+ 'Tregs', NKT cells, MAIT cells and B
      regulatory cells immune regulatory cell populations in cancer, with a particular
      focus on chronic lymphocytic leukaemia (CLL). We will discuss evidence linking
      CLL with immune regulatory dysfunction and the potential for new therapies
      targeting regulatory cells. 

PMID- 25862134
TI  - US Government warns against long-term dual use of conventional and e-cigarettes.

PMID- 25862132
TI  - Junctional complex and focal adhesion rearrangement mediates pulmonary
      endothelial barrier enhancement by FTY720 S-phosphonate.
AB  - RATIONALE: Modulation of pulmonary vascular barrier function is an important
      clinical goal given the devastating effects of vascular leak in acute lung injury
      (ALI). We previously demonstrated that FTY720 S-phosphonate (Tys), an analog of
      sphingosine 1-phosphate (S1P) and FTY720, has more potent pulmonary barrier
      protective effects than these agents in vitro and in mouse models of ALI. Tys
      preserves expression of the barrier-promoting S1P1 receptor (S1PR1), whereas S1P
      and FTY720 induce its ubiquitination and degradation. Here we further
      characterize the novel barrier promoting effects of Tys in cultured human
      pulmonary endothelial cells (EC). METHODS/RESULTS: In human lung EC, Tys
      significantly increased peripheral redistribution of adherens junction proteins
      VE-cadherin and beta-catenin and tight junction protein ZO-1. Inhibition of VE
      cadherin with blocking antibody significantly attenuated Tys-induced
      transendothelial resistance (TER) elevation, while ZO-1 siRNA partially inhibited
      this elevation. Tys significantly increased focal adhesion formation and
      phosphorylation of focal adhesion kinase (FAK). Pharmacologic inhibition of FAK
      significantly attenuated Tys-induced TER elevation. Tys significantly increased
      phosphorylation and peripheral redistribution of the actin-binding protein,
      cortactin, while cortactin siRNA partially attenuated Tys-induced TER elevation.
      Although Tys significantly increased phosphorylation of Akt and GSK3beta, neither
      PI3 kinase nor GSK3beta inhibition altered Tys-induced TER elevation. Tys
      significantly increased Rac1 activity, while inhibition of Rac1 activity
      significantly attenuated Tys-induced VE-cadherin redistribution and TER
      elevation. CONCLUSION: Junctional complex, focal adhesion rearrangement and Rac1
      activation play critical roles in Tys-mediated barrier protection in pulmonary
      EC. These results provide mechanistic insights into the effects of this potential
      ALI therapy.

PMID- 25862135
TI  - The Patient Protection and Affordable Care Act: politics and pills.

PMID- 25862136
TI  - Ambrisentan May Improve Exercise Tolerance and Cardiac Function in Patients With
      Pulmonary Hypertension.
AB  - PURPOSE: Pulmonary hypertension (PH) is characterized by a significant increase
      in pulmonary vascular resistance, which results in ventricular failure and death.
      Ambrisentan appears to be an effective treatment in the pathogenesis and
      progression of ambrisentan, but some researchers disagree. Therefore, this meta
      analysis aims to examine the clinical efficacy of ambrisentan in the treatment of
      PH. METHODS: A search of the scientific literature using the Embase, Cochrane,
      and CHINAHL databases retrieved published studies related to our topic of
      interest. Eight cohort studies related to ambrisentan and PH treatment were
      selected on the basis of our strict inclusion and exclusion criteria for a
      systematic meta-analysis. Statistical analyses were conducted using STATA version
      12.0 statistical software (StataCorp LP, College Station, Texas). FINDINGS: Our
      meta-analysis retrieved 124 studies using our search criteria (90 studies in
      English and 34 studies in Chinese), and 8 studies (4 studies in English and 4
      studies in Chinese) were eventually selected for this meta-analysis. The 8
      studies contained data on a total of 172 PH patients. Pooled data in our meta
      analysis revealed that 6-minute walking distance in PH patients significantly
      improved after ambrisentan treatment compared with before treatment. The mean
      pulmonary arterial pressure, brain natriuretic peptide level, and systolic
      pulmonary artery pressure in PH patients decreased measurably after ambrisentan
      treatment compared with before treatment. Sensitivity analysis results confirmed
      that the included studies had no publication bias (all P > 0.05). IMPLICATIONS:
      Our meta-analysis results demonstrated that ambrisentan is highly effective in
      improving exercise tolerance and cardiac function in PH patients, and the mean
      pulmonary arterial pressure, systolic pulmonary artery pressure, and brain
      natriuretic peptide level levels in PH patients significantly decreased. However,
      with the limitations of small sample size, insufficient data, and ethnic
      difference in the study, further studies with larger sample sizes and sufficient
      information are essential to validate our findings of the high safety profile and
      efficacy of ambrisentan in treatment of PH.

PMID- 25862137
TI  - Hypersensitivity Reactions to Oxaliplatin: Identifying the Risk Factors and
      Judging the Efficacy of a Desensitization Protocol.
AB  - PURPOSE: We examined the clinical data of patients treated with oxaliplatin to
      determine the risk factors of oxaliplatin-related hypersensitivity reaction
      (HSR). In addition, we evaluated the efficacy of rechallenging patients with HSRs
      with oxaliplatin using prophylactic agents or desensitization procedures.
      METHODS: This study consisted of 162 patients with colorectal cancer (88 men and
      74 women) who were treated consecutively at the outpatient chemotherapy
      department at University Hospital, Kyoto Prefectural University of Medicine.
      Patients underwent chemotherapy, including oxaliplatin, between March 2006 and
      June 2012. We analyzed the patients' clinical backgrounds (eg, age, sex,
      performance status, disease stage, and allergic history) to uncover any
      connections to the development of HSR to oxaliplatin. In addition, we
      rechallenged 10 patients who had oxaliplatin-related HSR using prophylactic
      agents or desensitization procedures. FINDINGS: Of 162 patients, 28 (17.2%)
      developed oxaliplatin-related HSRs (16, 2, 9 and 1 patient had grade 1, 2, 3, and
      4 HSRs, respectively). The total cumulative dose of oxaliplatin at the onset of
      the HSR was 301 to 1126 mg/m(2) (median, 582 mg/m(2)), and the first reactions
      developed in these patients after 5 to 17 infusions of oxaliplatin (median, 8
      infusions). Logistic regression analysis indicated that sex (male: odds ratio =
      3.624; 95% CI, 1.181-11.122; P = 0.024) and eosinophil count in peripheral blood
      (odds ratio = 35.118; 95% CI, 1.058-1166.007; P = 0.046) were independent
      variables for oxaliplatin-related HSRs. Rechallenging patients with prophylactic
      agents was successful in 2 (28.6%) of 7 patients who successfully completed their
      treatment. On the other hand, all 3 patients rechallenged with oxaliplatin using
      a desensitization protocol successfully completed their treatment without new
      HSRs. IMPLICATIONS: In this retrospective study, we observed that being male and
      having higher counts of peripheral eosinophil could be predictors for HSR to
      oxaliplatin. In addition, this study confirms that oxaliplatin desensitization
      protocol allows patients who developed HSRs to continue with their treatment.
      However, the optimum desensitization protocol for oxaliplatin administration in
      terms of tolerability and efficacy needs to be defined.

PMID- 25862138
TI  - Can the previous therapeutic control of the main risk factors of cerebrovascular
      disease influence the acetylsalicylic Acid-nonresponsive status in acute ischemic
      stroke patients? Results from a portuguese prospective cohort study.
AB  - BACKGROUND: Acute ischemic stroke (AIS) is a complex disease, and the therapeutic
      control of its risk factors may influence the efficacy of acetylsalicylic acid
      (ASA) and the occurrence of new vascular events. The aim of this study was to
      investigate the potential in vivo properties of a previous treatment controlling
      the main risk factors of cerebrovascular disease, in the ASA-nonresponsive status
      in a Portuguese population. METHODS: We conducted a prospective cohort study with
      the recruitment of 90 patients diagnosed with AIS and a follow-up protocol was
      set up with recurrent stroke as the main clinical end point under evaluation. At
      admission, PFA-100 (platelet function analyzer) test was evaluated in blood
      samples from AIS patients treated with 100 mg/day of ASA and previously treated
      with antihypertensive, antidiabetic, or statin drugs. RESULTS: We observed that
      30% of patients were ASA nonresponders. Multivariate regression analysis
      indicated that the previous treatment with antihypertensive drugs emerged with a
      significant risk reduction of an ASA-nonresponsive status (odds ratio, .119; 95%
      confidence interval, .026-.538; P = .006). Furthermore, our results indicated an
      influence of ASA-nonresponsive status in a decreased period to a new recurrent
      stroke event in the time frame of 24 months (P = .005, log-rank test).
      CONCLUSIONS: ASA is an important part of treatment of AIS, and its efficacy may
      be improved in previous high-risk cerebrovascular patients, particularly with
      antihypertensive therapeutic control.

PMID- 25862139
TI  - Exploring the Phenotypic Space and the Evolutionary History of a Natural Mutation
      in Drosophila melanogaster.
AB  - A major challenge of modern Biology is elucidating the functional consequences of
      natural mutations. Although we have a good understanding of the effects of
      laboratory-induced mutations on the molecular- and organismal-level phenotypes,
      the study of natural mutations has lagged behind. In this work, we explore the
      phenotypic space and the evolutionary history of a previously identified adaptive
      transposable element insertion. We first combined several tests that capture
      different signatures of selection to show that there is evidence of positive
      selection in the regions flanking FBti0019386 insertion. We then explored several
      phenotypes related to known phenotypic effects of nearby genes, and having
      plausible connections to fitness variation in nature. We found that flies with
      FBti0019386 insertion had a shorter developmental time and were more sensitive to
      stress, which are likely to be the adaptive effect and the cost of selection of
      this mutation, respectively. Interestingly, these phenotypic effects are not
      consistent with a role of FBti0019386 in temperate adaptation as has been
      previously suggested. Indeed, a global analysis of the population frequency of
      FBti0019386 showed that climatic variables explain well the FBti0019386 frequency
      patterns only in Australia. Finally, although FBti0019386 insertion could be
      inducing the formation of heterochromatin by recruiting HP1a (Heterochromatin
      Protein 1a) protein, the insertion is associated with upregulation of sra in
      adult females. Overall, our integrative approach allowed us to shed light on the
      evolutionary history, the relevant fitness effects, and the likely molecular
      mechanisms of an adaptive mutation and highlights the complexity of natural
      genetic variants. 

PMID- 25862140
TI  - Are Convergent and Parallel Amino Acid Substitutions in Protein Evolution More
      Prevalent Than Neutral Expectations?
AB  - Convergent and parallel amino acid substitutions in protein evolution,
      collectively referred to as molecular convergence here, have small probabilities
      under neutral evolution. For this reason, molecular convergence is commonly
      viewed as evidence for similar adaptations of different species. The surge in the
      number of reports of molecular convergence in the last decade raises the
      intriguing question of whether molecular convergence occurs substantially more
      frequently than expected under neutral evolution. We here address this question
      using all one-to-one orthologous proteins encoded by the genomes of 12 fruit fly
      species and those encoded by 17 mammals. We found that the expected amount of
      molecular convergence varies greatly depending on the specific neutral
      substitution model assumed at each amino acid site and that the observed amount
      of molecular convergence is explainable by neutral models incorporating site
      specific information of acceptable amino acids. Interestingly, the total number
      of convergent and parallel substitutions between two lineages, relative to the
      neutral expectation, decreases with the genetic distance between the two
      lineages, regardless of the model used in computing the neutral expectation. We
      hypothesize that this trend results from differences in the amino acids
      acceptable at a given site among different clades of a phylogeny, due to
      prevalent epistasis, and provide simulation as well as empirical evidence for
      this hypothesis. Together, our study finds no genomic evidence for higher-than
      neutral levels of molecular convergence, but suggests the presence of abundant
      epistasis that decreases the likelihood of molecular convergence between
      distantly related lineages. 

PMID- 25862141
TI  - Multiple Cross-Species Transmission Events of Human Adenoviruses (HAdV) during
      Hominine Evolution.
AB  - Human adenoviruses (HAdV; species HAdV-A to -G) are highly prevalent in the human
      population, and represent an important cause of morbidity and, to a lesser
      extent, mortality. Recent studies have identified close relatives of these
      viruses in African great apes, suggesting that some HAdV may be of zoonotic
      origin. We analyzed more than 800 fecal samples from wild African great apes and
      humans to further investigate the evolutionary history and zoonotic potential of
      hominine HAdV. HAdV-B and -E were frequently detected in wild gorillas (55%) and
      chimpanzees (25%), respectively. Bayesian ancestral host reconstruction under
      discrete diffusion models supported a gorilla and chimpanzee origin for these
      viral species. Host switches were relatively rare along HAdV evolution, with
      about ten events recorded in 4.5 My. Despite presumably rare direct contact
      between sympatric populations of the two species, transmission events from
      gorillas to chimpanzees were observed, suggesting that habitat and dietary
      overlap may lead to fecal-oral cross-hominine transmission of HAdV. Finally, we
      determined that two independent HAdV-B transmission events to humans occurred
      more than 100,000 years ago. We conclude that HAdV-B circulating in humans are of
      zoonotic origin and have probably affected global human health for most of our
      species lifetime. 

PMID- 25862142
TI  - Single Geographic Origin of a Widespread Autotetraploid Arabidopsis arenosa
      Lineage Followed by Interploidy Admixture.
AB  - Whole-genome duplication, which leads to polyploidy, has been implicated in
      speciation and biological novelty. In plants, many species exhibit ploidy
      variation, which is likely representative of an early stage in the evolution of
      polyploid lineages. To understand the evolution of such multiploidy systems, we
      must address questions such as whether polyploid lineage(s) had a single or
      multiple origins, whether admixture occurs between ploidies, and the timescale
      over which ploidy variation affects the evolution of populations. Here we analyze
      three genomic data sets using nonparametric and parametric analyses, including
      coalescent-based methods, to study the evolutionary history of a geographically
      widespread autotetraploid variant of Arabidopsis arenosa, a new model system for
      understanding the molecular basis of autopolyploid evolution. Autotetraploid A.
      arenosa populations are widely distributed across much of Northern and Central
      Europe, whereas diploids occur in Eastern Europe and along the southern Baltic
      coast; the two ploidies overlap in the Carpathian Mountains. We find that the
      widespread autotetraploid populations we sampled likely arose from a single
      ancestral population approximately 11,000-30,000 generations ago in the Northern
      Carpathians, where its closest extant diploid relatives are found today.
      Afterward, the tetraploid population split into at least four major lineages that
      colonized much of Europe. Reconstructions of population history suggest that
      substantial interploidy admixture occurred in both directions, but only among
      geographically proximal populations. We find two cases in which selection likely
      acted on an introgressed locus, suggesting that persistent interploidy gene flow
      has a local influence on patterns of genetic variation in A. arenosa. 

PMID- 25862143
TI  - A Randomized Controlled Trial To Assess and Compare the Outcomes of Two-core
      Prostate Biopsy Guided by Fused Magnetic Resonance and Transrectal Ultrasound
      Images and Traditional 12-core Systematic Biopsy.
AB  - BACKGROUND: Prostate biopsy guided by computer-assisted fusion of magnetic
      resonance imaging (MRI) and transrectal ultrasound (TRUS) images (MRI group) has
      not yet been compared with 12-core random biopsy (RB; control group) in a
      randomized controlled trial (RCT). OBJECTIVE: To compare the rate of detection of
      clinically significant prostate cancer (csPCa) between the two groups. DESIGN,
      SETTING, AND PARTICIPANTS: This RCT included 175 biopsy-naive patients with
      suspicion for prostate cancer, randomized to an MRI group (n=86) and a control
      group (n=89) between September 2011 and June 2013. INTERVENTION: In the MRI
      group, two-core targeted biopsy (TB) guided by computer-assisted fusion of
      MRI/TRUS images of MRI-suspicious lesions was followed by 12-core RB. In the
      control group, both two-core TB for abnormal digital rectal examination (DRE)
      and/or TRUS-suspicious lesions and 12-core RB were performed. In patients with
      normal MRI or DRE/TRUS, only 12-core RB was performed. OUTCOMES MEASUREMENTS AND
      STATISTICAL ANALYSIS: The detection rates for any cancer and csPCa were compared
      between the two groups and between TB and RB. RESULTS AND LIMITATIONS: Detection
      rates for any cancer (MRI group 51/86, 59%; control group 48/89, 54%; p=0.4) and
      csPCa (38/86, 44% vs 44/89, 49%; p=0.5) did not significantly differ between the
      groups. Detection of csPCa was comparable between two-core MRI/TRUS-TB (33/86,
      38%) and 12-core RB in the control group (44/89, 49%; p=0.2). In a subset
      analysis of patients with normal DRE, csPCa detection was similar between two
      core MRI/TRUS-TB (14/66, 21%) and 12-core RB in the control group (15/60, 25%;
      p=0.7). Among biopsy-proven csPCas in MRI group, 87% (33/38) were detected by
      MRI/TRUS-TB. The definition of csPCa was only based on biopsy outcomes.
      CONCLUSION: Overall csPCa detection was similar between the MRI and control
      groups. Two-core MRI/TRUS-TB was comparable to 12-core RB for csPCa detection.
      PATIENT SUMMARY: Our randomized controlled trial revealed a similar rate of
      prostate cancer detection between targeted biopsy guided by magnetic resonance
      imaging (MRI) and transrectal ultrasound (TRUS) and 12-core random biopsy. The
      traditional 12-core random biopsy may be replaced by two-core MRI/TRUS targeted
      biopsy for detection of clinically significant prostate cancer.

PMID- 25862144
TI  - Everolimus treatment for patients with autoimmune hepatitis and poor response to
      standard therapy and drug alternatives in use.
AB  - OBJECTIVE: Not all patients with autoimmune hepatitis (AIH) respond to standard
      medical therapy with corticosteroids and azathioprine. Such patients may develop
      end-stage liver disease with poor prognosis unless transplantation is considered.
      Alternatively, the introduction of new therapeutic strategies could potentially
      ameliorate deterioration of liver function. Patients in our tertiary center were
      selected for everolimus therapy when exhibiting nonresponse or intolerance to
      combinations of the standard and empirical drugs in use (e.g., mycophenolate
      mofetil, calcineurin inhibitors [CNIs]). We here report the efficacy of
      everolimus treatment of patients with AIH. MATERIALS AND METHODS: Seven patients
      (six female, mean age 47 years, range 22-62 years) in whom disease control could
      not be achieved with standard therapy or the alternative drugs in use were
      included. RESULTS: Treatment with everolimus induced a clear reduction of
      transaminases within 2 weeks. After 3-5 months three patients had normal alanine
      aminotransferase (ALT) levels (10-45 IU) and four patients had ALT levels below
      55 IU compared to a three- to fivefold elevated level prior to everolimus
      treatment. Sustained remission after 1 year of treatment was observed in three
      patients; in another two patients ALT was 45-68 U/L. Four patients in remission
      after 3 years were rebiopsied. Two showed no histological progression, and in two
      the fibrosis had decreased. Side effects noted were myalgias and minor bacterial
      infections not leading to discontinuation of the drug. CONCLUSION: Our experience
      indicates that everolimus may be of value in selected patients with therapy
      resistant AIH and comorbidity/side effects that excludes the use of CNIs.

PMID- 25862145
TI  - Has it become increasingly expensive to follow a nutritious diet? Insights from a
      new price index for nutritious diets in Sweden 1980-2012.
AB  - BACKGROUND: Health-related illnesses such as obesity and diabetes continue to
      increase, particularly in groups of low socioeconomic status. The increasing cost
      of nutritious food has been suggested as an explanation. OBJECTIVE: To construct
      a price index describing the cost of a diet adhering to nutritional
      recommendations for a rational and knowledgeable consumer and, furthermore, to
      investigate which nutrients have become more expensive to obtain over time.
      METHODS: Linear programming and goal programming were used to calculate two
      optimal and nutritious diets for each year in the interval under different
      assumptions. The first model describes the rational choice of a cost-minimizing
      consumer; the second, the choice of a consumer trying to deviate as little as
      possible from average consumption. Shadow price analysis was used to investigate
      how nutrients contribute to the diet cost. RESULTS: The cost of a diet adhering
      to nutritional recommendations has not increased more than general food prices in
      Sweden between 1980 and 2012. However, following nutrient recommendations
      increases the diet cost even for a rational consumer, particularly for vitamin D,
      iron, and selenium. The cost of adhering to the vitamin D recommendation has
      increased faster than the general food prices. CONCLUSIONS: Not adhering to
      recommendations (especially those for vitamin D) offers an opportunity for
      consumers to lower the diet cost. However, the cost of nutritious diets has not
      increased more than the cost of food in general between 1980 and 2012 in Sweden.

PMID- 25862146
TI  - PD-L1 is highly expressed in lung lymphoepithelioma-like carcinoma: A potential
      rationale for immunotherapy.
AB  - OBJECTIVES: Programmed cell death-ligand 1 (PD-L1) and driver mutations are found
      in non-small cell lung cancers (NSCLCs) and may be suitable targets for specific
      therapies, but their roles in lymphoepithelioma-like carcinoma (LELC) of the lung
      are unclear. MATERIALS AND METHODS: Sixty-six patients with pulmonary LELCs were
      investigated. Paraffin-embedded tumor sections were stained with PD-L1 antibody.
      Tumors with moderate-to-strong membrane staining in >=5% of tumor cells were
      positive for PD-L1 overexpression. The presence of driver mutations in the genes
      for epidermal growth factor receptor (EGFR), KRAS, and BRAF were examined by
      direct sequencing. Anaplastic lymphoma kinase (ALK) and ROS1 levels were
      determined by immunohistochemistry. Correlations of PD-L1 expression and driver
      mutations with clinicopathologic parameters were analyzed. RESULTS: The overall
      frequency of PD-L1 overexpression and EGFR mutation was 75.8% and 12.1%,
      respectively. No KRAS, BRAF, ALK or ROS1 aberrations could be detected. PD-L1
      expression was not associated with driver mutations. Multivariate analysis
      revealed that smoking and advanced stage were independent risk factors for poor
      overall survival, whereas PD-L1 positivity was not significantly associated with
      patient outcome. CONCLUSION: There are high PD-L1 expression and infrequent
      driver mutations in LELCs compared with conventional NSCLCs. The high expression
      of PD-L1 in EBV and inflammation associated LELC may provide a rationale for
      immunotherapy in this subtype of lung cancer.

PMID- 25862147
TI  - Comparative effectiveness of neoadjuvant chemoradiotherapy versus chemotherapy
      alone followed by surgery for patients with stage IIIA non-small cell lung
      cancer.
AB  - OBJECTIVES: The optimal neoadjuvant therapy prior to surgical resection of stage
      IIIA non-small cell lung cancer (NSCLC) is controversial, as data support both
      preoperative chemoradiotherapy (N-CRT) and chemotherapy (N-CTX). We evaluated the
      comparative effectiveness of N-CRT versus N-CTX in stage IIIA patients in the
      National Cancer Database (NCDB). METHODS: Patients in the NCDB with stage IIIA
      NSCLC treated with N-CRT or N-CTX and surgery between 2003 and 2005 were
      analyzed. Outcomes included overall survival (OS), residual nodal disease (RND),
      any adverse pathologic features (APF=RND or positive margins), and 30-day
      postoperative mortality (POPM). The survival impact of post-operative
      radiotherapy (PORT) after N-CTX was also investigated. RESULTS: The cohort
      consisted of 1076 patients: 700 (65%) underwent N-CRT. The 5-year OS for the
      entire cohort was 39% (39.2% N-CRT vs. 38.6% N-CTX, p=NS). On multivariable
      regression, there was no difference in OS between N-CRT versus N-CTX (p=0.70).
      However, N-CRT was associated with a lower independent risk of RND (odds ratio,
      OR, 0.75, p=0.02) and a lower risk of APF (OR 0.67, p=0.0023). Among N-CTX
      patients, PORT was associated with inferior survival in patients without APF
      (hazard ratio 1.68, p=0.01) but not with APF. N-CRT did not increase early POPM,
      readmission rates, or length of stay. CONCLUSION: There was no difference in
      overall survival between these two strategies, although N-CRT was associated with
      improved pathologic outcomes. These data support either treatment approach, but
      early surgical consultation is critical to ensure operability. The indications
      for PORT in patients without adverse pathologic factors require further
      investigation.

PMID- 25862148
TI  - Metabolic abnormalities are absent in patients with generalized pustular
      psoriasis.

PMID- 25862150
TI  - Risk of incident chronic kidney disease and end-stage renal disease in patients
      with psoriasis: A nationwide population-based cohort study.
AB  - BACKGROUND: Psoriasis is a chronic inflammatory dermatosis that has been
      associated with various cardiovascular and metabolic comorbidities, including
      myocardial infarction, stroke, and diabetes mellitus. Recently, there are studies
      reporting the association of psoriasis with renal diseases. OBJECTIVE: To
      evaluate the risk of incident chronic kidney disease (CKD) and end-stage renal
      disease (ESRD) in people with psoriasis. METHODS: We used the Taiwan's National
      Health Insurance Research Database to conduct a nationwide population-based
      cohort study to assess the risk of incident CKD and ESRD in people with psoriasis
      and to further evaluate the respective risk estimates in those with mild and
      severe psoriasis based on treatment patterns. RESULTS: A total of 4633 psoriatic
      patients and 922,534 nonpsoriatic controls were included. Severe psoriasis, but
      not mild psoriasis, was an independent risk factor of incident CKD and ESRD
      (adjusted hazard ratio being 1.90 (95% confidence interval 1.33-2.70) and 2.97
      (95% confidence interval 1.72-5.11), respectively) after adjustment for potential
      confounders including age, gender, comorbidities, and used of nonsteroidal anti
      inflammatory drugs (NSAIDs). Severe psoriasis remained an independent risk factor
      of incident CKD and ESRD after various sensitivity analyses after adjusting for
      the presence of osteoarthritis and/or rheumatoid arthritis, use of methotrexate
      and/or cyclosporine, and chronic use of NSAIDs for at least 2 months. Psoriatic
      arthritis was an effect modifier for CKD and ESRD. CONCLUSIONS: The associations
      of severe psoriasis with CKD and ESRD should be recognized. Assessment of renal
      function and avoidance of long-term use of nephrotoxic drugs shall be implemented
      in the integrative care for patients with severe psoriasis.

PMID- 25862149
TI  - Quantitative proteogenomic profiling of epidermal barrier formation in vitro.
AB  - BACKGROUND: The barrier function of the epidermis is integral to personal well
      being, and defects in the skin barrier are associated with several widespread
      diseases. Currently there is a limited understanding of system-level proteomic
      changes during epidermal stratification and barrier establishment. OBJECTIVE:
      Here we report the quantitative proteogenomic profile of an in vitro
      reconstituted epidermis at three time points of development in order to
      characterize protein changes during stratification. METHODS: The proteome was
      measured using data-dependent "shotgun" mass spectrometry and quantified with
      statistically validated label-free proteomic methods for 20 replicates at each of
      three time points during the course of epidermal development. RESULTS: Over 3600
      proteins were identified in the reconstituted epidermis, with more than 1200 of
      these changing in abundance over the time course. We also collected and discuss
      matched transcriptomic data for the three time points, allowing alignment of this
      new dataset with previously published characterization of the reconstituted
      epidermis system. CONCLUSION: These results represent the most comprehensive
      epidermal-specific proteome to date, and therefore reveal several aspects of
      barrier formation and skin composition. The limited correlation between
      transcript and protein abundance underscores the importance of proteomic analysis
      in developing a full understanding of epidermal maturation.

PMID- 25862151
TI  - Attachment security and recent stressful life events predict oxytocin levels: a
      pilot study of pregnant women with high levels of cumulative psychosocial
      adversity.
AB  - PURPOSE: Recent reports indicate that prenatal levels of the neuropeptide
      oxytocin (OT) are inversely related to depressive symptomatology and positively
      associated with more optimal interactive behaviors in mothers with high levels of
      cumulative psychosocial adversity (CPA). In the present pilot study, we aimed to
      identify factors associated with high versus low levels of OT in pregnant women
      with high levels of CPA. We hypothesized that insecurely attached women, and
      those who recently experienced stressful life events (SLE), would have lower
      levels of prenatal OT. METHODS: Thirty pregnant women with mood and anxiety
      disorders and high levels of CPA were recruited from the perinatal mental health
      service of a general hospital. Participants completed self-report measures of
      psychosocial stress and adult attachment style, and blood was then drawn to
      assess OT. RESULTS AND CONCLUSIONS: Lower OT levels were found among those who
      were insecurely attached, and among those who experienced SLE within the last
      year. In a multiple linear regression, both attachment security and SLE
      significantly contributed to a model of prenatal OT levels. These individual
      difference factors explained 38% of the variance in prenatal OT, which may in
      turn predict poorer maternal mental health and caregiving outcomes during the
      postpartum period.

PMID- 25862152
TI  - A Glycosylation Mutant of Trypanosoma brucei Links Social Motility Defects In
      Vitro to Impaired Colonization of Tsetse Flies In Vivo.
AB  - Transmission of African trypanosomes by tsetse flies requires that the parasites
      migrate out of the midgut lumen and colonize the ectoperitrophic space. Early
      procyclic culture forms correspond to trypanosomes in the lumen; on agarose
      plates they exhibit social motility, migrating en masse as radial projections
      from an inoculation site. We show that an Rft1(-/-) mutant needs to reach a
      greater threshold number before migration begins, and that it forms fewer
      projections than its wild-type parent. The mutant is also up to 4 times less
      efficient at establishing midgut infections. Ectopic expression of Rft1 rescues
      social motility defects and restores the ability to colonize the fly. These
      results are consistent with social motility reflecting movement to the
      ectoperitrophic space, implicate N-glycans in the signaling cascades for
      migration in vivo and in vitro, and provide the first evidence that parasite
      parasite interactions determine the success of transmission by the insect host. 

PMID- 25862153
TI  - Developmental Growth Control Exerted via the Protein A Kinase Tpk2 in Ashbya
      gossypii.
AB  - Sporulation in Ashbya gossypii is induced by nutrient-limited conditions and
      leads to the formation of haploid spores. Using RNA-seq, we have determined a
      gene set induced upon sporulation, which bears considerable overlap with that of
      Saccharomyces cerevisiae but also contains A. gossypii-specific genes. Addition
      of cyclic AMP (cAMP) to nutrient-limited media blocks sporulation and represses
      the induction of sporulation specific genes. Deletion of the protein kinase A
      (PKA) catalytic subunits encoded by TPK1 and TPK2 showed reduced growth in tpk1
      but enhanced growth in the tpk2 strain; however, both mutants sporulated well.
      Sporulation can be blocked by cAMP in tpk1 but not in tpk2 strains. Similarly,
      TPK2 acts at a second developmental switch promoting the break in spore dormancy.
      In S. cerevisiae, PKA phosphorylates and inhibits Msn2/4. The transcript profiles
      of the tpk1 and msn2/4 mutants were very similar to that of the wild type under
      sporulation conditions. However, deletion of the single A. gossypii MSN2/4
      homolog generated a specific sporulation defect. We identified a set of genes
      involved in spore wall assembly that was downregulated in the msn2/4 mutant,
      particularly DIT2, suggesting that poor spore viability may be due to lysis of
      spores. Our results reveal specific functional differences between the two
      catalytic PKA subunits in A. gossypii and identified Tpk2 as the key A kinase
      that transduces developmental decisions of growth. Our data also suggest that
      Msn2/4 is involved only at a late step of sporulation in A. gossypii and is not a
      major regulator of IME1. 

PMID- 25862154
TI  - Overlapping Functions between SWR1 Deletion and H3K56 Acetylation in Candida
      albicans.
AB  - Nucleosome destabilization by histone variants and modifications has been
      implicated in the epigenetic regulation of gene expression, with the histone
      variant H2A.Z and acetylation of H3K56 (H3K56ac) being two examples. Here we find
      that deletion of SWR1, the major subunit of the SWR1 complex depositing H2A.Z
      into chromatin in exchange for H2A, promotes epigenetic white-opaque switching in
      Candida albicans. We demonstrate through nucleosome mapping that SWR1 is required
      for proper nucleosome positioning on the promoter of WOR1, the master regulator
      of switching, and that its effects differ in white and opaque cells. Furthermore,
      we find that H2A.Z is enriched adjacent to nucleosome-free regions at the WOR1
      promoter in white cells, suggesting a role in the stabilization of a repressive
      chromatin state. Deletion of YNG2, a subunit of the NuA4 H4 histone
      acetyltransferase (HAT) that targets SWR1 activity through histone acetylation,
      produces a switching phenotype similar to that of swr1, and both may act
      downstream of the GlcNAc signaling pathway. We further uncovered a genetic
      interaction between swr1 and elevated H3K56ac with the discovery that the swr1
      deletion mutant is highly sensitive to nicotinamide. Our results suggest that the
      interaction of H2A.Z and H3K56ac regulates epigenetic switching at the nucleosome
      level, as well as having global effects. 

PMID- 25862155
TI  - Impact of Protein Palmitoylation on the Virulence Potential of Cryptococcus
      neoformans.
AB  - The localization and specialized function of Ras-like proteins are largely
      determined by posttranslational processing events. In a highly regulated process,
      palmitoyl groups may be added to C-terminal cysteine residues, targeting these
      proteins to specific membranes. In the human fungal pathogen Cryptococcus
      neoformans, Ras1 protein palmitoylation is essential for growth at high
      temperature but is dispensable for sexual differentiation. Ras1 palmitoylation is
      also required for localization of this protein on the plasma membrane. Together,
      these results support a model in which specific Ras functions are mediated from
      different subcellular locations. We therefore hypothesize that proteins that
      activate Ras1 or mediate Ras1 localization to the plasma membrane will be
      important for C. neoformans pathogenesis. To further characterize the Ras1
      signaling cascade mediating high-temperature growth, we have identified a family
      of protein S-acyltransferases (PATs), enzymes that mediate palmitoylation, in the
      C. neoformans genome database. Deletion strains for each candidate gene were
      generated by homogenous recombination, and each mutant strain was assessed for
      Ras1-mediated phenotypes, including high-temperature growth, morphogenesis, and
      sexual development. We found that full Ras1 palmitoylation and function required
      one particular PAT, Pfa4, and deletion of the PFA4 gene in C. neoformans resulted
      in altered Ras1 localization to membranes, impaired growth at 37 degrees C, and
      reduced virulence. 

PMID- 25862156
TI  - Incidence and risk factors of hemolysis after transcatheter aortic valve
      implantation with a balloon-expandable valve.
AB  - There are currently no data evaluating the hematologic and biocompatibility
      profile of transcatheter aortic valves in vivo. We evaluated the incidence,
      predictive factors, and clinical consequences associated with hemolysis post
      transcatheter aortic valve implantation (TAVI). A total of 122 patients who
      underwent TAVI with a balloon-expandable valve were included. Baseline blood
      sampling and echocardiography, followed by early post-TAVI echocardiography and
      repeat blood sampling, at 6 to 12 months post-TAVI were performed. Hemolysis post
      TAVI was defined according to the established criteria. The incidence of
      hemolysis post-TAVI was 14.8% yet no patient experienced severe hemolytic anemia
      requiring transfusion. Compared with the nonhemolysis group, those with hemolysis
      demonstrated significant reductions in hemoglobin (p = 0.012), were more
      frequently women (67% vs 34%, p = 0.016), and had a higher incidence of post-TAVI
      severe prosthesis-patient mismatch (PPM) (44% vs 17%, p = 0.026). The rate of
      mild or more prosthetic valve regurgitation did not significantly differ between
      those patients with and without hemolysis (56% vs 37%, p = 0.44). Wall shear rate
      (WSR) and energy loss index (ELI), both indirect measures of shear stress, were
      higher (p = 0.039) and lower (p = 0.004), respectively, in those patients with
      hemolysis. Increasing PPM severity was also associated with significant stepwise
      WSR increments and ELI decrements (p <0.01 for both). In conclusion, subclinical
      hemolysis occurred in 15% of patients following TAVI. Although prosthetic valve
      regurgitation had no impact on hemolysis, a novel association between PPM and
      hemolysis was found, likely driven by higher shear stress as determined by WSR
      and ELI. These hematologic and biomechanical findings may have long-term clinical
      implications and could affect future transcatheter aortic valve design. 

PMID- 25862157
TI  - Meta-Analysis of Relation Between Oral beta-Blocker Therapy and Outcomes in
      Patients With Acute Myocardial Infarction Who Underwent Percutaneous Coronary
      Intervention.
AB  - The aim of the present review was to investigate the association between the use
      of oral beta-blockers and prognosis in patients with acute myocardial infarction
      (AMI) who underwent percutaneous coronary intervention (PCI) treatment. A
      systematic literature search was conducted in Pubmed (from inception to September
      27, 2014) and Embase (Ovid SP, from 1974 to September 29, 2014) to identify
      studies that compared the outcome of patients with AMI taking oral beta-blockers
      with that of patients not taking after PCI. Systematic review and meta-analysis
      were performed with random-effects model or fixed-effects model. Ten
      observational studies with a total of 40,873 patients were included. Use of beta
      blockers was associated with a reduced risk of all-cause death (unadjusted
      relative risk 0.58, 95% confidential interval 0.48 to 0.71; adjusted hazard ratio
      0.76, 95% confidential interval 0.62 to 0.94). The potential benefit of beta
      blockers in preventing all-cause death was not similar in all population but was
      restricted to those with reduced ejection fraction, with low use proportion of
      other secondary prevention drugs or with non-ST-segment elevation myocardial
      infarction. The association between the use of beta-blockers and improved
      survival rate was significant in <=1-year follow-up duration. Rates of cardiac
      death, myocardial infarction, and heart failure readmission in patients using
      beta-blockers were not significantly different from those in patients without
      beta-blocker therapy. In conclusion, there is lack of evidence to support routine
      use of beta-blockers in all patients with AMI who underwent PCI. Further trials
      are urgently needed to address the issue.

PMID- 25862158
TI  - Blood pressure in 57,915 pediatric patients who are overweight or obese based on
      five reference systems.
AB  - The aim of this study was to determine the prevalence of hypertension in
      overweight or obese pediatric subjects using different national or international
      references, which are based either on the entire population or on normal weight
      children only: 188 centers from Germany, Austria, and Switzerland participated in
      the Adipositas Patienten Verlaufsbeobachtung initiative. Data from 57,915
      children aged 6 to 18 years who are overweight or obese were used to determine
      the prevalence of prehypertension and hypertension based on Second Task Force,
      European pooled data, Fourth Report all and Fourth Report nonoverweight, or
      German Health Interview and Examination Survey for Children and Adolescents
      (KiGGS) references. Three references included overweight children, whereas 2
      (Fourth Report nonoverweight and KiGGS) were based on nonoverweight children
      only. Based on KiGGS, Fourth Report nonoverweight, Fourth Report all, European
      pooled data, or Second Task Force, the prevalence of hypertension was 47%, 42%,
      36%, 32%, and 27%, respectively. Recent references classified more children as
      hypertensive, whereas fewer children fell into the prehypertensive group. Only
      22% of children were classified as hypertensive by each of the 5 references (8%
      as prehypertensive). The prevalence of normal blood pressure was independent of
      the reference applied. Hypertension as defined by the different reference systems
      was significantly correlated, and all methods were significantly associated with
      impaired glucose metabolism or dyslipidemia, without significant differences in
      methods. In conclusion, the diagnosis of elevated blood pressure depends on the
      reference population used. A nonoverweight reference population substantially
      increases the prevalence of hypertension in children and adolescents who are
      overweight or obese. The choice of the reference has significant implications for
      risk stratification and treatment decisions. 

PMID- 25862159
TI  - The potential of LINGO-1 as a therapeutic target for essential tremor.
AB  - INTRODUCTION: LINGO-1 is a negative regulator of neuronal survival,
      oligodendrocyte differentiation and axonal outgrowth and regeneration, because it
      interacts with diverse growth factor receptors blocking or inhibiting their
      action. Consistent findings obtained in vitro and in animal models suggest that
      anti-LINGO-1 therapy may be useful in neurodegenerative disorders such as
      multiple sclerosis (MS), Parkinson's disease or essential tremor (ET). Moreover,
      genetic and pathological evidence provide a robust link between LINGO-1 and ET.
      AREAS COVERED: In this review, we present an overview of current knowledge on
      findings linking LINGO-1 and ET, with a special focus on genetic linkage, we
      include an overview of LINGO1 gene variations according to the 1000 genomes
      catalog, and we identify potential gene areas where common changes occur because,
      as well as the risk developing ET, LINGO1 genetic changes may influence the
      response to anti-LINGO-1 therapy. EXPERT OPINION: The goal of anti-LINGO-1
      therapy in neurodegenerative diseases is to ease the brakes of neuronal growth
      and recovery. An anti-LINGO-1 antibody is under clinical trials for MS patients.
      Before planning trials with ET patients, refinement on the genetic link between
      LINGO1 and ET, and a detailed genetic and phenotypic assessment of ET patients to
      be enrolled, should be carried out.

PMID- 25862160
TI  - Rho family GTPases bring a familiar ring to cell wound repair.
AB  - Repair of wounds to single cells involves dynamic membrane and cytoskeletal
      rearrangements necessary to seal the wound and repair the underlying cytoskeleton
      cortex. One group of proteins essential to the cortical remodeling is the Rho
      family of small GTPases. Recently we showed that the founding members of this
      GTPases family, Rho, Rac, and Cdc42, are all essential for normal single cell
      wound repair and accumulate at the wound periphery in distinct temporal/spatial
      patterns in the Drosophila cell wound model. In addition, these proteins
      communicate with one another and with the cytoskeleton to regulate their
      distribution in response to wounds. Unexpectedly, we found evidence for context
      specific Rho GTPase binding to downstream targets or "effectors" which cannot be
      explained solely by means of local GTPase activation. Here we discuss these
      observations in relation to similar studies in single cell wound repair in the
      Xenopus oocyte, and highlight how these cell wound models serve as powerful tools
      to understand both cell wound repair and Rho GTPase biology. 

PMID- 25862161
TI  - A novel role of Rab11 in trafficking GPI-anchored trans-sialidase to the plasma
      membrane of Trypanosoma cruzi.
AB  - Trypanosoma cruzi, the causative agent of Chagas disease, is a unicellular
      parasite that possesses a contractile vacuole complex (CVC). This organelle is
      usually present in free-living protists and is mainly involved in osmoregulation.
      However, in some organisms, like for example Dictyostelium discoideum, other
      roles include calcium homeostasis and transference of proteins to the plasma
      membrane. T. cruzi plasma membrane is very rich in glycosylphosphatidylinositol
      anchored proteins (GPI-AP) and a very important group of GPI-AP is that of the
      trans-sialidases. These enzymes catalyze the transfer of sialic acid from host
      glycoconjugates to mucins present in the surface of the parasite and are
      important for host cell invasion among other functions. We recently reported that
      a pathway dependent on the Rab GTPase Rab11 is involved in the traffic of trans
      sialidases to the plasma membrane through the CVC of the infective stages of the
      parasite and that preventing this traffic results in considerable reduction in
      the ability of T. cruzi to infect host cells. We also found that traffic of other
      GPI-anchored proteins is also through the CVC but uses a Rab11-independent
      pathway. These represent unconventional pathways of GPI-anchored protein traffic
      to the plasma membrane. 

PMID- 25862162
TI  - Rho GEFs and GAPs: emerging integrators of extracellular matrix signaling.
AB  - Investigating cell migration in 3D settings has revealed that specific
      extracellular matrix environments require differential activities of the Rho
      GTPases for efficient migration. However, it is largely unknown how the
      activities of specific Rho GTPases are modulated to direct cell migration in
      response to different extracellular matrix cues. We have recently reported that
      extracellular matrix-dependent regulation of a specific Rho GEF is a fundamental
      mechanism governing cell migration in different microenvironments, providing a
      direct mechanism for extracellular matrix-specific regulation of Rho GTPase
      activity directing cell motility. We discovered that the Rho GEF betaPix has a
      unique function during cell migration in fibrillar collagen environments by
      restraining RhoA signaling through a conserved signaling axis involving Cdc42 and
      the Rho GAP srGAP1. In this Commentary, we expand upon this new pathway and
      discuss potential mechanotransductive and therapeutic applications. Additionally,
      we speculate on a generalized role for Rho GEFs and GAPs in providing localized,
      context-dependent responses to the cellular microenvironment during cell
      migration and other cellular processes. 

PMID- 25862163
TI  - Purification of nuclear localization signal-containing proteins and its
      application to investigation of the mechanisms of the cell division cycle.
AB  - The GTP bound form of the Ran GTPase (RanGTP) in the nucleus promotes nuclear
      import of the proteins bearing nuclear localization signals (NLS). When nuclear
      envelopes break down during mitosis, RanGTP is locally produced around
      chromosomes and drives the assembly of the spindle early in mitosis and the
      nuclear envelope (NE) later. RanGTP binds to the heterodimeric nuclear transport
      receptor importin alpha/beta and releases NLS proteins from the receptor.
      Liberated NLS proteins around chromosomes have been shown to play distinct,
      essential roles in spindle and NE assembly. Here we provide a highly specific
      protocol to purify NLS proteins from crude cell lysates. The pure NLS fraction is
      an excellent resource to investigate the NLS protein function and identify new
      mitotic regulators, uncovering fundamental mechanisms of the cell division cycle.
      It takes 2-3 days to obtain the NLS fraction. 

PMID- 25862164
TI  - Rho family GTPase functions in Drosophila epithelial wound repair.
AB  - Epithelial repair in the Drosophila embryo is achieved through 2 dynamic
      cytoskeletal machineries: a contractile actomyosin cable and actin-based cellular
      protrusions. Rho family small GTPases (Rho, Rac, and Cdc42) are cytoskeletal
      regulators that control both of these wound repair mechanisms. Cdc42 is necessary
      for cellular protrusions and, when absent, wounds are slow to repair and never
      completely close. Rac proteins accumulate at specific regions in the wound
      leading edge cells and Rac-deficient embryos exhibit slower repair kinetics.
      Mutants for both Rho1 and its effector Rok impair the ability of wounds to close
      by disrupting the leading-edge actin cable. Our studies highlight the importance
      of these proteins in wound repair and identify a downstream effector of Rho1
      signaling in this process. 

PMID- 25862165
TI  - Integration of the Rac1- and actin-binding properties of Coronin-1C.
AB  - The coronin family of actin-binding proteins regulate actin branching by
      inhibiting Arp2/3. We recently reported 2 interactions that were unique to
      coronin-1C: binding of a Rac1 inhibitor, RCC2, to the unique linker region and
      Rac1 itself to the propeller domain in a manner that differs from that proposed
      for other coronins. Through these interactions coronin-1C redistributes Rac1 from
      the back of the cell to the leading edge for either activation or sequestration
      by the associated Rac1-inhibitor, RCC2. Here we investigate the relationship
      between the Rac1- and actin-binding properties of coronin-1C and find that,
      although actin appears to be involved in the retrafficking of Rac1, signaling by
      Rac1 lies upstream of the stress fiber-formation, for which the coronins were
      originally characterized. 

PMID- 25862168
TI  - Lower NPAS3 expression during the later stages of abnormal lung development in
      rat congenital diaphragmatic hernia.
AB  - PURPOSE: Congenital diaphragmatic hernia (CDH) is characterized by a
      developmental defect in the diaphragm, pulmonary hypoplasia and pulmonary
      hypertension. NPAS3 is a PAS domain transcription factor regulating Drosophila
      tracheogenesis. NPAS3 null mice develop pulmonary hypoplasia in utero and die
      after birth due to respiratory failure. We aimed to evaluate NPAS3 expression
      during normal and abnormal lung development due to CDH. METHODS: CDH was induced
      by administering 100 mg/ml nitrofen to time-pregnant dams on embryonic day (E) 9
      of gestation. Lungs were isolated on E15, E18 and E21 and NPAS3 localization was
      determined by immunohistochemistry and quantified using Western blotting.
      RESULTS: We found that only E21 hypoplastic CDH lungs have reduced expression of
      NPAS3 in the terminal saccules. Western blotting confirmed the down-regulation of
      NPAS3 protein in the nitrofen-induced hypoplastic lungs. CONCLUSIONS: We
      demonstrate for the first time that nitrofen-induced hypoplastic CDH lungs have
      reduced NPAS3 expression in the terminal saccules during the later stages of
      abnormal lung development. Our findings suggest that NPAS3 is associated with
      pulmonary hypoplasia in CDH.

PMID- 25862169
TI  - Oxidative stress shapes breast cancer phenotype through chronic activation of ATM
      dependent signaling.
AB  - Reactive oxygen species (ROS) are thought to be among the initiating insults that
      drive carcinogenesis; however, beyond the mutagenic properties of ROS, it is
      unclear how reactive oxygen species and response to redox imbalance may shape
      cancer phenotype. We have previously observed that basal activity of the
      powerfully oncogenic transcription factor NF-kappaB in cultured breast cancer and
      other tumor cell lines is dependent upon the DNA damage-responsive kinase ATM.
      Here we show that, in MDA-MB-231 and HeLa cells, basal ATM-dependent NF-kappaB
      activation occurs through a canonical DNA damage-responsive signaling pathway as
      knockdown of two proteins involved in this signaling pathway, ERC1 and TAB1,
      results in loss of NF-kappaB basal activity. We further show that knockdown of
      ATM in MDA-MB-231, a breast cancer line with a pronounced mesenchymal phenotype,
      results in the reversion of these cells to an epithelial morphology and gene
      expression pattern. Culture of MDA-MB-231 and HeLa cells on the antioxidant N
      acetyl cysteine (NAC) blunted NF-kappaB transcriptional activity, and long-term
      culture on low doses of NAC resulted in coordinate reductions in steady-state ROS
      levels, acquisition of an epithelial morphology, as well as upregulation of
      epithelial and downregulation of mesenchymal marker gene expression. Moreover,
      these reversible effects are attributable, at least in part, to downregulation of
      ATM-dependent NF-kappaB signaling in MDA-MB-231 cells as RNAi-mediated knockdown
      of the NF-kappaB subunit RelA or its upstream activator TG2 produced similar
      alterations in phenotype. We conclude that chronic activation of ATM in response
      to persistent ROS insult triggers continual activation of the oncogenic NF-kappaB
      transcriptional complex that, in turn, promotes aggressive breast cancer
      phenotype. 

PMID- 25862171
TI  - The Swiss Prospective Autologous Bone Flap Resorption Study (SPARS): a
      multicentric approach to quantify the complication rate after reimplantation of
      autologous cryoconserved bone flaps.

PMID- 25862170
TI  - Feasibility of diffusion tensor tractography for preoperative prediction of the
      location of the facial and vestibulocochlear nerves in relation to vestibular
      schwannoma.
AB  - BACKGROUND: According to recent findings, diffusion tensor tractography (DTT)
      only allows prediction of facial nerve location in relation to vestibular
      schwannoma (VS) with high probability. However, previous studies have not
      mentioned why only the facial nerve was selectively visualized. Our previous
      report investigated the optimal conditions of DTT for normal facial and
      vestibulocochlear nerves. In the present study, we applied the optimal conditions
      of DTT to VS patients to assess the feasibility of DTT for the facial and
      vestibulocochlear nerves. METHODS: We investigated 11 patients with VS who
      underwent tumor resection. Visualized tracts were compared with locations of the
      facial and cochlear nerves as identified by intraoperative electrophysiological
      monitoring. RESULTS: With the proposed method, visualized tracts corresponded to
      pathway area of the facial or cochlear nerves in nine of 11 patients (81.8%);
      specifically, to the pathway area of the facial nerve in three of 11 patients
      (27.3%), and to the pathway area of the cochlear nerve in six of 11 patients
      (54.5%). CONCLUSIONS: We visualized facial or vestibulocochlear nerves in nine of
      11 patients (81.8%). For the first time, DTT proved able to visualize not only
      the facial nerve but also the vestibulocochlear nerve in VS patients. Despite our
      findings, good methods for distinguishing whether a visualized nerve tract
      represents facial nerve, vestibulocochlear nerve, or only noise remain
      unavailable. Close attention should therefore be paid to the interpretation of
      visualized fibers.

PMID- 25862172
TI  - The first radiographic image of a peripheral nerve disorder? Lipomatous
      macrodactyly (unrecognized lipomatosis of nerve).
AB  - Lipomatosis of nerves (LN) involves benign fibro-fatty infiltration and is often
      associated with territorial overgrowth of soft tissue and bone; this distinctive
      disease pattern can be visualized on plain radiographs. We recently discovered a
      case (presented by Sir Robert Jones in 1898 to the Pathological Society of
      London) that indirectly represents a historical landmark in the imaging of
      peripheral nerves. The clinical findings and image, with obvious soft tissue and
      bone overgrowth, are pathognomonic for LN, making this one of the earliest
      radiological observations of a peripheral nerve lesion.

PMID- 25862173
TI  - A new classification and clinical results of Gamma Knife radiosurgery for
      cavernous sinus hemangiomas: a report of 53 cases.
AB  - BACKGROUND: Cavernous sinus hemangiomas (CaSHs) are rare vascular lesions in the
      cavernous sinus(CS). Gamma Knife radiosurgery (GKS) provides a treatment modality
      alternative to microsurgery. This study was conducted to describe a new
      classification of CaSHs based on their magnetic resonance (MR) imaging findings
      and determine the efficacy and safety of GKS in a large series of CaSH patients.
      METHODS: From April 2007 to November 2012, 53 patients harboring CaSHs were
      treated using Leksell Gamma Knife model C (before April 2012) or Perfexion (from
      May 2012 ) at the Gamma Knife Center of Huashan Hospital. Of the 53 patients, 15
      with definitive histopathologic diagnoses after surgery, 38 were diagnosed based
      on their MR imaging findings. There were 15 male and 38 female patients with a
      mean age of 52 (range, 25-76) years old. The characteristics of MR images of
      CaSHs were their extremely high homogeneous intensity on T2-weighted and FLAIR
      images: as bright as cerebrospinal fluid signal. According to the relationship
      between the carotid line and their location, CaSHs were classified into three
      types: the intrasellar, parasellar and mixed type. The mean volume of the tumors
      was 13.2 +/- 8.2 cm(3) (range, 1-41 cm(3)). A mean marginal dose of 13.3 Gy
      (range, 8-15 Gy) was directed to the 49%-64% isodose line (mean 53%). RESULTS: Of
      the 53 tumors, 6 (11%) were classified as intrasellar type. Eight (15%) were
      parasellar type and the other 39 cases(74%) mixed type. The mean radiological and
      clinical follow-up time of this study was 24 (range, 2-67 months) and 34 months
      (range, 2-73 months), respectively. The tumor control rate was 100%. The mean
      tumor volume reduction was 79.5% (range, 16.5%-100%) compared with the pre-GKS
      volume. Six months after GKS, MR imaging revealed an average of 60.2% tumor
      volume reduction (range, 16.5%-89.2%). Twenty-nine cases (55%) showed a >80%
      tumor volume decrease. Neurologically, only two of these patients showed clinical
      deterioration, and 33 patients demonstrated an obvious improvement in ocular or
      endocrine disorders. At last follow-up, there were no more complications related
      to GKS, and none of the tumors progressed. CONCLUSIONS: Our study showed that GKS
      is a useful and safe therapeutic method for CaSHs as both a primary and adjuvant
      treatment. The new classification of CaSHs may help predict their clinical course
      during tumor development and treatment response after GKS. Further studies with
      long-term follow-up and larger numbers of cases are necessary to optimize the
      treatment conditions and verify the benefit of this treatment.

PMID- 25862174
TI  - Erratum to: Tumor burden evaluation in NF1 patients with plexiform neurofibromas
      in daily clinical practice.

PMID- 25862175
TI  - The PNPLA3 p.Ile148Met Variant and Obesity: brothers-in-arms: Comment on: PNPLA3
      genotype increases susceptibility of nonalcoholic steatohepatitis among obese
      patients with nonalcoholic fatty liver disease.

PMID- 25862176
TI  - Inflammation and iron status in bariatric surgery candidates.
AB  - BACKGROUND: Iron homeostasis is disturbed by the systemic inflammation commonly
      encountered in morbid obesity. However, inflammatory markers have seldom been
      considered in studies investigating the prevalence of iron deficiency (ID) in
      bariatric surgery (BS) candidates. The objective of this study was to evaluate
      the prevalence of ID and anemia with ID in BS candidates, accounting for
      inflammatory status as measured using high sensitivity C-reactive protein (hs
      CRP), and to further characterize indices of iron status in BS candidates with
      systemic inflammation. PATIENTS AND METHODS: On the basis of ferritin,
      hemoglobin, and hs-CRP levels, iron status was categorized in 803 (85%) of 947
      consecutive BS candidates. Ferritin<12 ng/mL in females and<15 ng/mL in males
      irrespective of hs-CRP level was classified as absolute-ID, whereas ferritin
      between those thresholds and 100 ng/mL was categorized as functional-ID (FID) if
      hs-CRP>3 mg/L. Anemia was defined as hemoglobin<12 or<13 g/dL in females and
      males, respectively. Additional iron and hematological indices were assessed in
      patients with FID. RESULTS: Prevalence of absolute- and functional-ID was 8.7 and
      52.5%, respectively. Anemia was found in 11.2% of the cohort, 80% of which were
      associated with ID. Among patients with FID, transferrin saturation (T-Sat)<20%
      was common (70.0%) and associated with larger impairment of hematological
      indices. CONCLUSION: The data show that when hs-CRP as inflammatory marker and
      ferritin as iron index are considered, impaired iron status could be identified
      in approximately two thirds of BS candidates. Furthermore, T-Sat<20%, especially
      along with ferritin<30 ng/mL, appear to be practical cut-offs to identify
      patients with FID with larger iron status impairment.

PMID- 25862177
TI  - Laparoscopic total gastrectomy as an alternative treatment to postsleeve chronic
      fistula.
AB  - BACKGROUND: Sleeve gastrectomy (SG) has become a very common 1-stage procedure in
      bariatric surgery. Postsleeve chronic fistulas could be one of the possible
      complications and represent a true challenge for the surgeons. After the failure
      of more conservative treatments, including surgical and endoscopic approaches,
      laparoscopic total gastrectomy (LTG) could be an alternative treatment proposal.
      The objective of this study was to evaluate outcomes of patients who underwent
      laparoscopic total gastrectomy for the treatment of postsleeve chronic fistula.
      METHODS: Retrospectively review the data from patients after LTG for postsleeve
      chronic fistula who had failed in all previous treatment attempts with a
      combination of conservative, endoscopic, and/or surgical approach. RESULTS: From
      January 2008 to December 2012, 12 patients underwent LTG. Mean time from SG to
      LTG was 16 months (ranged from 6 to 30). All patients had undergone several
      previous treatment attempts, including endoscopic techniques (fibrin glue, clips,
      pneumatic dilation, and stents) and surgical procedures for abscess drainage.
      Surgical time ranged from 4 to 7 hours with a mean hospital stay of 6 days.
      Complications occurred in 2 patients (17%) with 1 revision as a result of an
      intestinal occlusion. There were no conversions to open surgery, anastomotic
      leaks, or deaths. CONCLUSIONS: LTG was feasible in the management of postsleeve
      chronic fistulas recalcitrant to other treatment approaches with a few
      complications and high rate of resolution.

PMID- 25862178
TI  - Comment on: Indications and outcomes of reversal of Roux-en-Y gastric bypass.

PMID- 25862179
TI  - Enhanced glucose metabolism in cultured human skeletal muscle after Roux-en-Y
      gastric bypass surgery.
AB  - BACKGROUND: Roux-en-Y gastric bypass (RYGB) surgery rapidly increases whole body
      insulin sensitivity, with changes in several organs including skeletal muscle.
      Objectives were to determine whether improvements in insulin action in skeletal
      muscle may occur directly at the level of the myocyte or secondarily from changes
      in systemic factors associated with weight loss. Myotubes were derived before and
      after RYGB surgery. The setting was Karolinska University Hospital and Karolinska
      Institutet, Stockholm, Sweden. METHODS: Eight patients (body mass index (BMI)
      41.8 kg/m(2); age 41 yr) underwent RYGB surgery. Before and 6 months after RYGB
      surgery, skeletal muscle biopsies were collected from vastus lateralis muscle.
      Satellite cells derived from skeletal muscle biopsies were propagated in vitro as
      myoblasts and differentiated into myotubes. RESULTS: Expression of myogenic
      markers is increased in myoblasts derived from biopsies taken 6 months after
      bypass surgery, compared with their respective presurgery condition. Furthermore,
      glycogen synthesis, tyrosine phosphorylation of insulin receptor (IRS)-1-Tyr612
      and Interleukin (IL)-8 secretion were increased, while fatty acid oxidation and
      circulating IL8 levels remain unaltered. Myotubes derived from muscle biopsies
      obtained after RYGB surgery displayed increased insulin-stimulated
      phosphorylation of protein kinase B (PKB)-Thr308 and proline-rich Akt substrate
      of 40 kDa (PRAS40)-Thr246. CONCLUSIONS: RYGB surgery is accompanied by enhanced
      glucose metabolism and insulin signaling, altered IL8 secretion and changes in
      mRNA levels and myogenic markers in cultured skeletal muscle cells. Thus, RYGB
      surgery involves intrinsic reprogramming of skeletal muscle to increase
      peripheral insulin sensitivity and glucose metabolism.

PMID- 25862180
TI  - Long-Term outcomes and experience of laparoscopic adjustable gastric banding: one
      center's results in China.
AB  - BACKGROUND: Laparoscopic adjustable gastric banding (LAGB), as one major
      bariatric surgery for treatment of obesity, results in ineffective long-term
      weight loss and a high reoperation rate. The objective of this study was to
      evaluate the long-term effects of LAGB on the weight loss outcomes and
      reoperation rates of obese patients with different body mass index (BMI) levels
      in China. METHODS: A retrospective study was performed to review the follow-up
      data of obese patients who underwent LAGB at Shanghai Changhai Hospital between
      November 2003 and May 2013. The main outcomes included weight loss, percentage
      excess weight loss (%EWL), reoperation rate, and reasons for reoperation.
      RESULTS: A total of 254 LAGB procedures were performed in our hospital. By the
      end of May 2013, 145 Chinese patients (57.8%) were followed up, 99 patients with
      BMI >= 35 kg/m(2) (high BMI group) and 46 patients with BMI < 35 kg/m(2) (low BMI
      group). In the high BMI group, the mean %EWL was > 25% within 5 years
      postoperatively, but it decreased to less than 25% after 5 years. However, in the
      low BMI group, the mean %EWL at each time point was over 50%. The reoperation
      rate was 33.1%; it was 17.4% in the low BMI group and 34.3% in the high BMI
      group. CONCLUSION: LAGB is more effective with a lower reoperation rate for obese
      patients with a BMI < 35 kg/m(2) compared to BMI >= 35 kg/m(2) in our population.

PMID- 25862181
TI  - The rationale for a duodenal switch as the primary surgical treatment of advanced
      type 2 diabetes mellitus and metabolic disease.

PMID- 25862183
TI  - Nitrosative stress but not glycemic parameters correlate with improved neuropathy
      in nonseverely obese diabetic patients after Roux-Y gastric bypass.
AB  - BACKGROUND: Diabetic neuropathy is common in type 2 diabetic patients (T2DM) but
      tight glycemic control does not improve the symptoms. In contrast, Roux-Y gastric
      bypass (RYGB) has a positive effect on active neuropathic symptoms, independent
      from glycemic control. The purpose of the present study was to identify potential
      mechanisms of improved diabetic neuropathic symptoms after RYGB. METHODS: A
      prospective cohort of 20 patients with insulin-dependent T2DM and BMI < 35
      kg/m(2) were treated with RYGB. Nineteen patients had complete follow-up. Fasting
      glucose, HbA1c (glycated hemoglobin), markers for nitrosative, carbonyl, and
      oxidative stress (nitrotyrosine, carboxylated-lysine (CML), methylglyoxal,
      oxidized low-density-lipoprotein (oxLDL)) as well as Neuropeptid Y and Neurokinin
      A were investigated over 12 months. Neuropathy was assessed using the Neuropathy
      Deficit Score (NDS). RESULTS: The preoperative NDS improved within twelve months
      (5.1 +/- 0.6 to 2.6 +/- 0.4, P = .010). Fasting glucose and HbA1c also improved
      compared to preoperative values (201.1 +/- 16.6 mg/dL to 128 +/- 8.7 mg/dL, P =
      .004 and 8.5 +/- 0.3% (53 +/- 3.3 mmol/mol) to 7 +/- 0.3% (67 +/- 3.3 mmol/mol),
      P = .001, respectively). Nitrotyrosine, CML, and methylglyoxal all 3 decreased
      postoperatively (1067.3 +/- 266.9 nM to 355.8 +/- 36.4 nM, P = .003; 257.1 +/-
      10.2 ng/ml to 215.3 +/- 18.3 ng/ml, P = .039; 402.3 +/- 3.9 nM to 163.4 +/- 10.3
      nM, P = .002). OxLDL remained unchanged. Fasting glucose and HbA1c did not
      correlate with improved neuropathy. The decrease in nitrotyrosine correlated with
      improvement in the NDS after 6 and twelve months (r = .9, P < .001 and r = .68, P
      = .03). The decrease in methylglyoxal after 6 months correlated with decrease in
      NDS after twelve months (r = 0.897, P = .003). CONCLUSION: RYGB seems to improve
      oxidative, nitrosative and carbonyl stress, known to have a causal role in
      diabetic neuropathy.

PMID- 25862182
TI  - Addictive disorders after Roux-en-Y gastric bypass.
AB  - BACKGROUND: Recent literature suggests that some patients may develop addictive
      disorders after bariatric surgery, in particular after Roux-en-Y gastric bypass
      (RYGB). These may include traditional addictions and so called "behavioral
      addictions," although prevalence data on the latter have not been published. The
      objective of this study was to establish the prevalence of addictive behaviors in
      adults after RYGB. METHODS: Participants from a large observational study of
      bariatric surgery who had undergone RYGB were recruited to complete additional
      measures. Of 241 consented participants, 201 provided data (i.e., Structured
      Clinical Interview for DSM-IV Axis I [SCID], additional Impulsive Control
      Disorder Modules, and various self-report measures, including the Alcohol Use
      Disorder Identification Test [AUDIT]) to assess status before surgery and in the
      first 3 postoperative years. RESULTS: Based on the SCID, 16 (8.0%) developed
      alcohol use disorder [AUD] within 3 years post-RYGB, 7 (43.8%) of whom had no
      history of AUD. When both the SCID and AUDIT were used to identify AUD, the
      corresponding numbers/percentages were 32 (18.4%) and 13 (40.6%). Data on other
      behavioral addictive disorders indicated 19 (9.5%) had a postsurgery disorder, 6
      (31.6%) of whom had no history. CONCLUSION: These data add to a growing
      literature suggesting there is a substantial risk for the development of AUD
      after bariatric surgery. Understanding the risk for nondrug-related addictive
      disorders requires more data from larger studies before clear conclusions can be
      drawn.

PMID- 25862184
TI  - Sleeve gastrectomy improves obstructive sleep apnea syndrome (OSAS): 5 year
      longitudinal study.
AB  - BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is prevalent among morbidly
      obese patients. Evaluation of the specific effects of sleeve gastrectomy (SG) on
      upper airway function has not been reported. Given the possibility that some
      patients will not respond despite weight loss, no studies have investigated
      whether other mechanisms may be responsible for persistent OSAS after bariatric
      surgery. OBJECTIVES: To evaluate by subjective and objective assessment the
      impact of SG on upper respiratory physiology in the long-term. SETTING:
      University Hospital, Division of Bariatric and ENT Surgery, in Italy. METHODS:
      Thirty-six consecutive patients with OSAS who underwent laparoscopic SG were
      prospectively enrolled. The effect of SG on respiratory function and OSAS was
      followed for 5 years. RESULTS: All patients completed the 5-year follow-up. A
      significant (P<.001) improvement in modified Epworth Sleepiness Scale
      questionnaire (ESS) was obtained in 91.6% (33/36) of patients. The Apnea/Hypopnea
      index (AHI) improved in 80.6% (29/36) of patients after surgery (from 32.8 +/-
      1.7 to 5.8 +/- 1.2 (P<.001), 4.9 +/- 1.7). The remaining 19.4% (7/36) of patients
      with a positive ESS and/or AHI all had an associated respiratory resistance due
      to nasal obstructive diseases. CONCLUSION: SG improved OSAS overall, but patients
      who did not improve or only partially improved despite weight loss were found to
      have an associated nasal responsible pathology. How these patients will respond
      to nasal surgery and whether a 2-step procedure should be recommended for OSAS
      patients requires further study.

PMID- 25862185
TI  - Laparoscopic conversion of failed vertical banded gastroplasty to Roux-en-Y
      gastric bypass or biliopancreatic diversion.
AB  - BACKGROUND: The Silastic ring vertical gastroplasty (SRVG), a modification of
      Mason's vertical banded gastroplasty (VBG), was the restrictive procedure of
      choice for many bariatric surgeons. The reoperation rate for
      failure/complications reported in long-term studies is approximately 50%.
      OBJECTIVE: We report our experience in laparoscopic conversion of failed SRVG to
      Roux-en-Y gastric bypass (RYGB) and biliopancreatic diversion (BPD). SETTING: A
      single surgeon's experience at a university-affiliated hospital. METHODS: Between
      March 2006 and April 2014, 39 patients underwent conversion of SRVG to
      laparoscopic RYGB (n = 25) or BPD (n = 14). The outcomes were retrieved from a
      prospectively collected database and analyzed. RESULTS: Most (89%) of the
      conversions were completed laparoscopically. The mean operative time was 195 and
      200 min for RYGB and BPD, respectively. There was no mortality. Complications
      occurred in 11 patients (28%), 5 in RYGB (19%) and 6 in BPD (42%). At the 3-year
      follow-up, the mean body mass index decreased from 47+/-8 kg/m(2) to 26+/-4
      kg/m(2) for BPD, and from 43 kg/m(2) to 34 kg/m(2) (P = .05) for RYGB. Weight
      (kg) decreased from 110 to 84 and to 92, and from 123 to 81 and 68, at 1 and 3
      years for RYGB and BPD, respectively. CONCLUSIONS: The weight loss for RYGB and
      BPD was equal at 1 year but tended to be better for BPD at 3 years
      postoperatively. Laparoscopic conversion of failed VBG to RYGB or BPD was
      feasible, but it was followed by prohibitively high complication rates in BPD
      patients. The risk:benefit ratio of these procedures in this series is
      questionable.

PMID- 25862186
TI  - Formation and Dissociation of the Interstrand i-Motif by the Sequences d(XnC 4Y
      m) Monitored with Electrospray Ionization Mass Spectrometry.
AB  - Formation and dissociation of the interstrand i-motifs by DNA with the sequence
      d(X(n)C(4)Y(m)) (X and Y represent thymine, adenine, or guanine, and n, m range
      from 0 to 2) are studied with electrospray ionization mass spectrometry (ESI-MS),
      circular dichroism (CD), and UV spectrophotometry. The ion complexes detected in
      the gas phase and the melting temperatures (Tm) obtained in solution show that a
      non-C base residue located at 5' end favors formation of the four-stranded
      structures, with T > A > G for imparting stability. Comparatively, no rule is
      found when a non-C base is located at the 3' end. Detection of penta- and hexa
      stranded ions indicates the formation of i-motifs with more than four strands. In
      addition, the i-motifs seen in our mass spectra are accompanied by single-,
      double-, and triple-stranded ions, and the trimeric ions were always less
      abundant during annealing and heat-induced dissociation process of the DNA
      strands in solution (pH = 4.5). This provides a direct evidence of a strand-by
      strand formation and dissociation pathway of the interstrand i-motif and
      formation of the triple strands is the rate-limiting step. In contrast, the
      trimeric ions are abundant when the tetramolecular ions are subjected to
      collision-induced dissociation (CID) in the gas phase, suggesting different
      dissociation behaviors of the interstrand i-motif in the gas phase and in
      solution. Furthermore, hysteretic UV absorption melting and cooling curves reveal
      an irreversible dissociation and association kinetic process of the interstrand i
      motif in solution.

PMID- 25862187
TI  - Determining the Binding Sites of beta-Cyclodextrin and Peptides by Electron
      Capture Dissociation High Resolution Tandem Mass Spectrometry.
AB  - Cyclodextrins (CDs) are a group of cyclic oligosaccharides, which readily form
      inclusion complexes with hydrophobic compounds to increase bioavailability, thus
      making CDs ideal drug excipients. Recent studies have also shown that CDs exhibit
      a wide range of protective effects, preventing proteins from aggregation,
      degradation, and folding. These effects strongly depend on the binding sites on
      the protein surface. CDs only exhibit weak interactions with amino acids,
      however; conventional analytical techniques therefore usually fail to reveal the
      exact location of the binding sites. Moreover, some studies even suggest that CD
      inclusion complexes are merely electrostatic adducts. Here, electron capture
      dissociation (ECD) was applied in this proof-of-concept study to examine the
      exact nature of the CD/peptide complexes, and CD binding sites were unambiguously
      located for the first time via Fourier-transform ion cyclotron resonance (FTICR)
      tandem mass spectrometry.

PMID- 25862188
TI  - Extensive Charge Reduction and Dissociation of Intact Protein Complexes Following
      Electron Transfer on a Quadrupole-Ion Mobility-Time-of-Flight MS.
AB  - Non-dissociative charge reduction, typically considered to be an unwanted side
      reaction in electron transfer dissociation (ETD) experiments, can be enhanced
      significantly in order to reduce the charge state of intact protein complexes to
      as low as 1+ on a commercially available Q-IM-TOF instrument. This allows for the
      detection of large complexes beyond 100,000 m/z, while at the same time
      generating top-down ETD fragments, which provide sequence information from
      surface-exposed parts of the folded structure. Optimization of the supplemental
      activation has proven to be crucial in these experiments and the charge-reduced
      species are most likely the product of both proton transfer (PTR) and non
      dissociative electron transfer (ETnoD) reactions that occur prior to the ion
      mobility cell. Applications of this approach range from deconvolution of complex
      spectra to the manipulation of charge states of gas-phase ions.

PMID- 25862189
TI  - Capsule Commentary on Newman et al., Yelp for Prescribers: A Quasi-Experimental
      Study of Providing Antibiotic Cost Data and Prescription of High-Cost Antibiotics
      in an Academic and Tertiary Care Hospital.

PMID- 25862190
TI  - National Survey of Medical Spanish Curriculum in U.S. Medical Schools.
AB  - BACKGROUND: Patients with limited English proficiency (LEP) may be at risk for
      medical errors and worse health outcomes. Language concordance between patient
      and provider has been shown to improve health outcomes for Spanish-speaking
      patients. Nearly 40 % of Hispanics, a growing population in the United States,
      are categorized as having limited English proficiency. Many medical schools have
      incorporated a medical Spanish curriculum to prepare students for clinical
      encounters with LEP patients. OBJECTIVE: To describe the current state of medical
      Spanish curricula at United States medical schools. METHODS: The Latino Medical
      Student Association distributed an e-mail survey comprising 39 items to deans
      from each U.S. medical school from July 2012 through July 2014. This study was
      IRB-exempt. RESULTS: Eighty-three percent (110/132) of the U.S. medical schools
      completed the survey. Sixty-six percent (73/110) of these schools reported
      offering a medical Spanish curriculum. In addition, of schools with no
      curriculum, 32 % (12/37) planned to incorporate the curriculum within the next
      two years. Most existing curricula were elective, not eligible for course credit,
      and taught by faculty or students. Teaching modalities included didactic
      instruction, role play, and immersion activities. Schools with the curriculum
      reported that the diverse patient populations in their respective service areas
      and/or student interest drove course development. Barriers to implementing the
      curriculum included lack of time in students' schedules, overly heterogeneous
      student language skill levels, and a lack of financial resources. Few schools
      reported the use of validated instruments to measure language proficiency after
      completion of the curriculum. CONCLUSIONS: Growing LEP patient populations and
      medical student interest have driven the implementation of medical Spanish
      curricula at U.S. medical schools, and more schools have plans to incorporate
      this curriculum in the near future. Studies are needed to reveal best practices
      for developing and evaluating the curriculum.

PMID- 25862191
TI  - Community Health Workers: A Missing Piece of the Puzzle for Complex Patients With
      Diabetes?

PMID- 25862192
TI  - Neurotrophic Effects of Mu Bie Zi (Momordica cochinchinensis) Seed Elucidated by
      High-Throughput Screening of Natural Products for NGF Mimetic Effects in PC-12
      Cells.
AB  - Post-mitotic central nervous system (CNS) neurons have limited capacity for
      regeneration, creating a challenge in the development of effective therapeutics
      for spinal cord injury or neurodegenerative diseases. Furthermore, therapeutic
      use of human neurotrophic agents such as nerve growth factor (NGF) are limited
      due to hampered transport across the blood brain barrier (BBB) and a large number
      of peripheral side effects (e.g. neuro-inflammatory pain/tissue degeneration
      etc.). Therefore, there is a continued need for discovery of small molecule NGF
      mimetics that can penetrate the BBB and initiate CNS neuronal
      outgrowth/regeneration. In the current study, we conduct an exploratory high
      through-put (HTP) screening of 1144 predominantly natural/herb products (947
      natural herbs/plants/spices, 29 polyphenolics and 168 synthetic drugs) for
      ability to induce neurite outgrowth in PC12 dopaminergic cells grown on rat tail
      collagen, over 7 days. The data indicate a remarkably rare event-low hit ratio
      with only 1/1144 tested substances (<111.25 ug/mL) being capable of inducing
      neurite outgrowth in a dose dependent manner, identified as; Mu Bie Zi, Momordica
      cochinchinensis seed extract (MCS). To quantify the neurotrophic effects of MCS,
      36 images (n = 6) (average of 340 cells per image), were numerically assessed for
      neurite length, neurite count/cell and min/max neurite length in microns (um)
      using Image J software. The data show neurite elongation from 0.07 +/- 0.02 um
      (controls) to 5.5 +/- 0.62 um (NGF 0.5 MUg/mL) and 3.39 +/- 0.45 um (138 MUg/mL)
      in MCS, where the average maximum length per group extended from 3.58 +/- 0.42 um
      (controls) to 41.93 +/- 3.14 um (NGF) and 40.20 +/- 2.72 um (MCS). Imaging
      analysis using immunocytochemistry (ICC) confirmed that NGF and MCS had similar
      influence on 3-D orientation/expression of 160/200 kD neurofilament, tubulin and
      F-actin. These latent changes were associated with early rise in phosphorylated
      extracellular signal-regulated kinase (ERK) p-Erk1 (T202/Y204)/p-Erk2 (T185/Y187)
      at 60 min with mild changes in pAKT peaking at 5 min, and no indication of pMEK
      involvement. These findings demonstrate a remarkable infrequency of natural
      products or polyphenolic constituents to exert neurotrophic effects at low
      concentrations, and elucidate a unique property of MCS extract to do so. Future
      research will be required to delineate in depth mechanism of action of MCS,
      constituents responsible and potential for therapeutic application in CNS
      degenerative disease or injury.

PMID- 25862193
TI  - Mephedrone and nicotine: oxidative stress and behavioral interactions in animal
      models.
AB  - The purpose of our experiment was to examine the influence of co-administration
      of nicotine and mephedrone on anxiety-like behaviors, cognitive processes and the
      nicotine-induced behavioral sensitization as well as processes connected with
      induction of oxidative stress in the brain of male Swiss mice. The results
      revealed that co-administration of subthreshold doses of mephedrone and nicotine
      (0.05 mg/kg each) exerted marked anxiogenic profile in the elevated plus maze and
      displayed pro-cognitive action in the passive avoidance paradigm (nicotine 0.05
      mg/kg and mephedrone 2.5 mg/kg). Furthermore, one of the main findings of the
      present study was that mephedrone, administered alone at the dose not affecting
      locomotor activity of mice (1 mg/kg), enhanced the expression of nicotine-induced
      locomotor sensitization. Moreover, mephedrone administered with nicotine
      decreased general antioxidant status and catalase activity as well as antioxidant
      enzymes activity in the hippocampus and prefrontal cortex and increased
      concentration of malondialdehyde, an indicator of lipid peroxidation processes.
      Considering the likelihood that mephedrone is taken as a part of polydrug
      combination with nicotine, the effects of this combination on mammalian organisms
      have been confirmed in our study. Understanding the consequences of co
      administration of psychoactive substances on the central nervous system and
      oxidative processes in the brain provide the important toxicological
      significance, and may be useful in polydrug intoxication treatment.

PMID- 25862195
TI  - Genotyping of Acinetobacter baumannii strains isolated at a Japanese hospital
      over five years using targeted next-generation sequencing.
AB  - Acinetobacter baumannii is a Gram-negative bacterial agent involved in nosocomial
      infections. In this five-year retrospective study, phylogenetic relationships
      among carbapenem-resistant A. baumannii strains that were isolated at Teikyo
      University Hospital in Tokyo metropolis, Japan, were explored. A panel of 72
      carbapenem-resistant A. baumannii strains that isolated from January 2006 until
      August 2010 was studied. Next-Generation sequencing (NGS) was employed to perform
      large-scale genotyping of these isolates. They were separated, according to the
      time of isolation, into two genetically distinct groups, one correspondent to
      strains of the outbreak reported to local public health department in 2010 and
      the other contained strains from earlier isolations, suggesting different origins
      of the isolates. Moreover, taxa in each group showed two main clustering
      patterns. Multilocus sequence typing (MLST) study on 8 isolates from the last
      outbreak showed that they were from one sequence type, 92, displaying less
      discriminatory power comparing to large-sequence typing. The clonal lineage
      profiles produced in this retrospective study will be used as a reference
      database to compare future isolations of A. baumannii. This study demonstrates
      the power of NGS in conducting epidemiological researches, allowing a high
      resolution genotyping.

PMID- 25862194
TI  - Uptake, Metabolic Effects and Toxicity of Arsenate and Arsenite in Astrocytes.
AB  - The inorganic arsenic species arsenate and arsenite are common environmental
      toxins which contaminate the drinking water in many countries. Chronic
      intoxication with arsenicals has been connected with various diseases, but causes
      also neurological complications and impairs cognitive development, learning and
      memory. In brain, astrocytes have a pivotal role as partners of neurons in
      homeostatic and metabolic processes. In addition, astrocytes are the first
      parenchymal brain cell type which encounters substances which cross the blood
      brain barrier and are considered as first line of defence against the toxic
      potential of xenobiotics. Therefore, astrocytes are likely to play a prominent
      role in the metabolism and potential detoxification of arsenicals in brain. This
      article summarizes the current knowledge on the uptake and toxicity of arsenate
      and arsenite in astrocytes and discusses the modulation of the astrocytic glucose
      and glutathione metabolism by arsenicals. 

PMID- 25862196
TI  - Present situation and challenges of vaccinations for overseas travelers from
      Japan.
AB  - The vaccination rates of Japanese people travelling abroad are still relatively
      low compared to travelers from Europe and the U.S. The following 3 causes are
      considered to contribute to the low vaccination rates among Japanese. First point
      is the lack of attention to the prevention of diseases during overseas travel in
      Japanese people. Second point is the limited number of healthcare facilities
      where Japanese overseas travelers can receive vaccinations. Third, many vaccines
      administered to travelers are still unapproved in Japan. However, there appear to
      be recent developments in each matter. With these social changes, the vaccination
      rate should be improved by disseminating recognition of the importance of the
      travel medicine in Japan. This report summarizes the present situation of
      vaccination of Japanese overseas travelers and discusses the challenges to
      improving vaccination rates. 

PMID- 25862197
TI  - Facile design of organic-inorganic hybrid gels for molecular recognition of
      nucleoside triphosphates.
AB  - We report the molecular recognition for nucleoside triphosphates inside the
      ligand-modified water-soluble organic-inorganic hybrid gels composed of
      polyhedral oligomeric silsesquioxane (POSS). The series of ligands were designed
      to make hydrogen bonds with each nucleobase and introduced into the hybrid gels.
      From the titration experiments, the binding constants between the ligand inside
      the gels and nucleosides were evaluated. Accordingly, it was found that the
      ligands inside the gels can form a stable complex only with the target nucleoside
      triphosphate which has the complementary pattern of the hydrogen bonds (Ka=G
      gel/cytidine triphosphate (CTP), 3.5*10(8)M(-1); U-gel/adenosine triphosphate
      (ATP), 1.6*10(3)M(-1); A-gel/uridine triphosphate (UTP), 1.9*10(7),
      respectively). With other nucleoside derivatives which have different numbers of
      phosphate units or different types of nucleobases, the much weaker interaction
      was detected. These data indicate that the complex formation only with nucleoside
      triphosphates should occur inside the hybrid gels, and selective recognition of
      each nucleoside triphosphate can be accomplished. 

PMID- 25862198
TI  - Elimination of a cholecystokinin receptor agonist 'trigger' in an effort to
      develop positive allosteric modulators without intrinsic agonist activity.
AB  - Cholecystokinin (CCK) acts at the type 1 cholecystokinin receptor (CCK1R) to
      elicit satiety and is a well-established drug target for obesity. To date, small
      molecule agonists have been developed, but have failed to demonstrate adequate
      efficacy in clinical trials, and concerns about side effects and potential
      toxicity have limited further development of full agonists. The use of positive
      allosteric modulators (PAMs) without intrinsic agonist activity that are active
      only for a brief period of time after a meal might represent a safer alternative.
      Here, we propose a possible novel strategy to develop such compounds by modifying
      the agonist 'trigger' of an existing small molecule agonist. We have studied
      analogues of the 1,5-benzodiazepine agonist, GI181771X, in which the N1-isopropyl
      agonist 'trigger' was modified. While agonist activity was greatly reduced in
      these compounds, they acted as negative, rather than positive modulators. The
      parent drug was also found to exhibit no positive modulation of CCK action.
      Receptor structure-activity relationship studies demonstrated that the mode of
      docking these derivatives was distinct from that of the parent compound, perhaps
      explaining their action as negative allosteric modulators. We conclude that this
      outcome is likely characteristic of the parental agonist, and that this strategy
      may be more successfully utilized with a parental ago-PAM, possessing intrinsic
      positive modulatory activity. 

PMID- 25862199
TI  - Cytotoxic and antioxidant constituents from the leaves of Psidium guajava.
AB  - Psidium guajava (Myrtaceae) is an evergreen shrub growing extensively throughout
      the tropical and subtropical areas. Four new compounds, guavinoside C, D, E and F
      (1-3, 10) were isolated from the leaves of P. guajava, along with six known ones
      (4-9). Their structures were elucidated by spectroscopic analysis. Compounds 1, 4
      and 10 showed significant cytotoxic activities on HeLa, SGC-7901 and A549 cell
      lines, respectively. Compounds 1 and 4-10 showed antioxidant activities in DPPH,
      ABTS and FRAP assays, and five of them (1, 4-6, 10) exhibited stronger activities
      than that of vitamin C. 

PMID- 25862200
TI  - Structure-activity relationship studies of the lipophilic tail region of
      sphingosine kinase 2 inhibitors.
AB  - Sphingosine-1-phosphate (S1P) is a ubiquitous, endogenous small molecule that is
      synthesized by two isoforms of sphingosine kinase (SphK1 and 2). Intervention of
      the S1P signaling pathway has attracted significant attention because alteration
      of S1P levels is linked to several disease states including cancer, fibrosis, and
      sickle cell disease. While intense investigations have focused on developing
      SphK1 inhibitors, only a limited number of SphK2-selective agents have been
      reported. Herein, we report our investigations on the structure-activity
      relationship studies of the lipophilic tail region of SLR080811, a SphK2
      selective inhibitor. Our studies demonstrate that the internal phenyl ring is a
      key structural feature that is essential in the SLR080811 scaffold. Further, we
      show the dependence of SphK2 activity and selectivity on alkyl tail length,
      suggesting a larger lipid binding pocket in SphK2 compared to SphK1. 

PMID- 25862201
TI  - Structure-activity relationships of IKM-159: Diverted synthesis and biological
      evaluation of a series of C5-oxy analogs.
AB  - Ligands for neuronal receptors are important for understanding the biological
      functions as well as for treatment of neuronal diseases associated with. Here, we
      report diverted synthesis and biological evaluation of four C-ring analogs of IKM
      159, a subtype-selective inhibitor for (S)-2-amino-3-(3-hydroxy-5-methyl-4
      isoxazolyl)propionic acid (AMPA)-type ionotropic glutamate receptor. Starting
      from iodinated 7-oxanorbornene 7, those analogs 3-6 were successfully synthesized
      in 7.0-33% yields over 8-11 steps via a common intermediate 13.
      Intracerebroventricular injection of those analogs on mice showed that
      introduction of oxo group on the C-ring (analogs 4, 5) or cleavage of the C-ring
      (analog 6) caused significant loss of the activity, while the ether analog 3
      still retain the suppressed motor activity, indicating the importance of the C
      ring in the neuronal activity of IKM-159. 

PMID- 25862202
TI  - The effects of income on mental health: evidence from the social security notch.
AB  - BACKGROUND: Mental health is a key component of overall wellbeing and mental
      disorders are relatively common, including among older adults. Yet the causal
      effect of income on mental health status among older adults is poorly understood.
      AIMS: This paper considers the effects of a major source of transfer income,
      Social Security retirement benefits, on the mental health of older adults.
      METHODS: The Social Security benefit "Notch" is as a large, permanent, and
      exogenous shock to Social Security income in retirement. The "Notch" is used to
      identify the causal effect of Social Security income on mental health among older
      ages using data from the AHEAD cohort of the Health and Retirement Study.
      RESULTS: We find that increases in Social Security income significantly improve
      mental health status and the likelihood of a psychiatric diagnosis for women, but
      not for men. DISCUSSION: The effects of income on mental health for older women
      are statistically significant and meaningful in magnitude. While this is one of
      the only studies to use plausibly exogenous variation in household income to
      identify the effect of income on mental health, a limitation of this work is that
      the results only directly pertain to lower-education households. IMPLICATIONS:
      Public policy proposals that alter retirement benefits for the elderly may have
      important effects on the mental health of older adults.

PMID- 25862203
TI  - Legislations and policies to expand mental health and substance abuse benefits in
      health insurance plans: a community guide systematic economic review.
AB  - BACKGROUND: Health insurance plans have historically limited the benefits for
      mental health and substance abuse (MH/SA) services compared to benefits for
      physical health services. In recent years, legislative and policy initiatives in
      the U.S. have been taken to expand MH/SA health insurance benefits and achieve
      parity with physical health benefits. The relevance of these legislations for
      international audiences is also explored, particularly for the European context.
      AIMS OF THE STUDY: This paper reviews the evidence of costs and economic benefits
      of legislative or policy interventions to expand MH/SA health insurance benefits
      in the U.S. The objectives are to assess the economic value of the interventions
      by comparing societal cost to societal benefits, and to determine impact on costs
      to insurance plans resulting from expansion of these benefits. METHODS: The
      search for economic evidence covered literature published from January 1950 to
      March 2011 and included evaluations of federal and state laws or rules that
      expanded MH/SA benefits as well as voluntary actions by large employers. Two
      economists screened and abstracted the economic evidence of MH/SA benefits
      legislation based on standard economic and actuarial concepts and methods.
      RESULTS: The economic review included 12 studies: eleven provided evidence on
      cost impact to health plans, and one estimated the effect on suicides. There was
      insufficient evidence to determine if the intervention was cost-effective or cost
      saving. However, the evidence indicates that MH/SA benefits expansion did not
      lead to any substantial increase in costs to insurance plans, measured as a
      percentage of insurance premiums. DISCUSSION AND LIMITATIONS: This review is
      unable to determine the overall economic value of policies that expanded MH/SA
      insurance benefits due to lack of cost-effectiveness and cost-benefit studies,
      predominantly due to the lack of evaluations of morbidity and mortality outcomes.
      This may be remedied in time when long-term MH/SA patient-level data becomes
      available to researchers. A limitation of this review is that legislations
      considered here have been superseded by recent legislations that have stronger
      and broader impacts on MH/SA benefits within private and public insurance: Mental
      Health Parity and Addiction Equity Act of 2008 (MHPAEA) and the Patient
      Protection and Affordable Care Act of 2010 (ACA). IMPLICATIONS FOR FUTURE
      RESEARCH: Economic assessments over the long term such as cost per QALY saved and
      cost-benefit will be feasible as more data becomes available from plans that
      implemented recent expansions of MH/SA benefits. Results from these evaluations
      will allow a better estimate of the economic impact of the interventions from a
      societal perspective. Future research should also evaluate the more downstream
      effects on business decisions about labor, such as effects on hiring, retention,
      and the offer of health benefits as part of an employee compensation package.
      Finally, the economic effect of the far reaching ACA of 2010 on mental health and
      substance abuse prevalence and care is also a subject for future research.

PMID- 25862204
TI  - The mental health consequences of nonmedical prescription drug use among
      adolescents.
AB  - BACKGROUND: Nonmedical prescription drug use is estimated to be the second most
      abused category of drugs after marijuana among adolescents. Prescription drugs
      can be highly addictive and prolonged use can produce neurological changes and
      physiological dependence and could result in adverse mental health outcomes. This
      topic is largely unexplored, as current knowledge of possible mechanisms of the
      linkage between adverse mental health consequences and prescription drug misuse
      is limited. AIM OF THE STUDY: This study explores the relationship between
      nonmedical use of prescription drugs and depression outcomes among adolescents.
      Given their complex and confounded relationship, our purpose is to better
      understand the extent to which nonmedical use of prescription drugs is an
      antecedent of depressive episodes. METHODS: Using data from the 2008-2012
      National Survey on Drug Use and Health, the study employs a propensity score
      matching methodology to ascertain whether nonmedical use of prescription drugs is
      linked to major depressive episodes among adolescents. RESULTS: The results
      document a positive relationship between nonmedical prescription drug use and
      major depressive episodes among adolescents. Specifically, the results indicate
      that adolescents who used prescription drugs non-medically are 33% to 35% more
      likely to experience major depressive episodes compared to their non-abusing
      counterparts. IMPLICATIONS FOR HEALTH POLICY: This provides additional evidence
      about the potential public health consequences of misuse of prescription drugs on
      adverse mental health outcomes. Given the significant increased risk of major
      depressive episode among adolescents who use prescription drugs nonmedically, it
      seems that the prevention of nonmedical prescription drug use warrants the
      utilization of both educational and public health resources. IMPLICATIONS FOR
      FUTURE RESEARCH: An important area for future research is to understand how any
      policy initiatives in this area must strike a balance between the need to
      minimize the misuse of prescription drugs and the need to ensure access for their
      legitimate health care use.

PMID- 25862205
TI  - Regional analysis of health service utilisation by persons with borderline
      personality disorders: implications for evidence-informed policy.
AB  - BACKGROUND: Borderline Personality Disorder (BPD) has been associated with an
      intensive use of health resources and a high economic burden. AIMS OF THE STUDY:
      The aim of this study is to analyze the use of mental healthcare resources by BPD
      patients, to identify the information gaps on BPD at the regional health
      databases and to describe specific indicators and patterns of care utilization by
      persons with BPD in order to guide evidence-informed policy planning in Catalonia
      (Spain). METHODS: A multi-level cross-design synthesis approach was applied
      following a mixed quantitative-qualitative analysis to estimate the regional
      service utilisation of patients with BPD. This framing analysis included
      estimates based on all available data on the use of services combined with prior
      expert knowledge gathered through a nominal group of key stakeholders in this
      field. RESULTS: The estimated year prevalence of BPD was 0.7% but only 9.6% of
      all BPD patients in Catalonia had any contact with the health care system. Of
      those, less than half contacted mental health care. BPD represented 1.7% of the
      total care load in the community mental health centres. A significant information
      gap was identified in all the official databases and impeded their direct use for
      planning and resource allocation in BPD. Expert knowledge was required to
      estimate rates of care utilization at every level of care system (primary care,
      specialized outpatient care and hospital care). Nevertheless the high pattern of
      care utilization identified at the databases was accurate according to the
      experts. DISCUSSION: Detection of BPD was lower than expected in the local,
      regional and national databases and registries of Catalonia. Local data was
      judged highly inaccurate by experts in comparison to data available on other
      mental disorders in the same databases. IMPLICATIONS FOR HEALTH POLICY AND
      RESEARCH: Specific incentives should be implemented to improve the availability
      and accuracy of information on BPD at the regional databases. When present, BPD
      should be coded before other psychiatric disorders in clinical records and health
      databases. Mental health surveys and psychiatric epidemiological studies should
      specifically incorporate BPD in their inclusion criteria and further studies on
      the utilisation pattern of this disorder are needed, both locally and
      internationally.

PMID- 25862206
TI  - GPs want longer consultations, BMA survey finds.

PMID- 25862207
TI  - Reactance and resistance: main properties to follow the cell differentiation
      process in Bacillus thuringiensis by dielectric spectroscopy in real time.
AB  - During growth, Bacillus thuringiensis presents three phases: exponential phase
      (EP), transition state (TS), and sporulation phase (SP). In order to form a
      dormant spore and to synthesize delta-endotoxins during SP, bacteria must undergo
      a cellular differentiation process initiated during the TS. Dielectric
      spectroscopy is a technique that can be utilized for continuous and in situ
      monitoring of the cellular state. In order to study on-line cell behavior in B.
      thuringiensis cultures, we conducted a number of batch cultures under different
      conditions, by scanning 200 frequencies from 42 Hz to 5 MHz and applying fixed
      current and voltage of 20 mA and 5 V DC, respectively. The resulting signals
      included Impedance (Z), Angle phase (Deg), Voltage (V), Current (I), Conductance
      (G), Reactance (X), and Resistance (R). Individual raw data relating to observed
      dielectric property profiles were correlated with the different growth phases
      established using data from cellular growth, cry1Ac gene expression, and free
      spores obtained with conventional techniques and fermentation parameters. Based
      on these correlations, frequencies of 0.1, 0.5, and 1.225 MHz were selected for
      the purpose of measuring dielectric properties in independent batch cultures, at
      a fixed frequency. X and R manifest more propitious behavior in relation to EP,
      TS, SP, and spore release, due to particular changes in their signals.
      Interestingly, these profiles underwent pronounced changes during EP and TS that
      were not noticed when using conventional methods, but were indicative of the
      beginning of the B. thuringiensis cell differentiation process. 

PMID- 25862208
TI  - Different Patterns in Health Care Use Among Immigrants in Spain.
AB  - This study aims to analyze the differences in the use of primary care (PC),
      hospital, and emergency services between people born in Spain and immigrants.
      Data were obtained from the 2006 Spanish National Health Survey. The sample was
      composed of individuals aged 16-64 years from Spain and the seven countries with
      most immigrants in Spain (n = 22,224). Hierarchical multiple logistic regression
      models were fitted. Romanian men were less likely to use health care at all
      levels compared to men from other countries. Women from Argentina, Bolivia and
      Ecuador reported a lower use of PC. Among women, there were no differences in
      emergency visits or hospitalizations between countries. Bolivian men reported
      more hospitalizations than Spanish men, whereas Argentinean men reported more
      emergency visits than their Spanish counterparts. In Spain, most immigrants made
      less than, or about the same use of health care services as the native Spanish
      population.

PMID- 25862209
TI  - Synthesis and biological evaluation of novel selective androgen receptor
      modulators (SARMs). Part I.
AB  - To develop effective drugs for hypogonadism, sarcopenia, and cachexia, we
      designed, synthesized, and evaluated selective androgen receptor modulators
      (SARMs) that exhibit not only anabolic effects on organs such as muscles and the
      central nervous system (CNS) but also neutral or antagonistic effects on the
      prostate. Based on the information obtained from a docking model with androgen
      receptor (AR), we modified a hit compound A identified through high-throughput
      screening. Among the prepared compounds, 1-(4-cyano-1-naphthyl)-2,3-disubstituted
      pyrrolidine derivatives 17h, 17m, and 17j had highly potent AR agonistic
      activities in vitro and good tissue selectivity in vivo. These derivatives
      increased the weight of the levator ani muscle without influencing the prostate
      and seminal vesicle. In addition, these compounds induced sexual behavior in
      castrated rats, indicating that the compounds could also act as agonists on the
      CNS. 

PMID- 25862210
TI  - Identification of N-ethylmethylamine as a novel scaffold for inhibitors of
      soluble epoxide hydrolase by crystallographic fragment screening.
AB  - Soluble epoxide hydrolase (sEH) is a potential target for the treatment of
      inflammation and hypertension. X-ray crystallographic fragment screening was used
      to identify fragment hits and their binding modes. Eight fragment hits were
      identified via soaking of sEH crystals with fragment cocktails, and the co
      crystal structures of these hits were determined via individual soaking. Based on
      the binding mode, N-ethylmethylamine was identified as a promising scaffold that
      forms hydrogen bonds with the catalytic residues of sEH, Asp335, Tyr383, and
      Tyr466. Compounds containing this scaffold were selected from an in-house
      chemical library and assayed. Although the starting fragment had a weak
      inhibitory activity (IC50: 800MUM), we identified potent inhibitors including 2
      ({[2-(adamantan-1-yl)ethyl]amino}methyl)phenol exhibiting the highest inhibitory
      activity (IC50: 0.51MUM). This corresponded to a more than 1500-fold increase in
      inhibitory activity compared to the starting fragment. Co-crystal structures of
      the hit compounds demonstrate that the binding of N-ethylmethylamine to catalytic
      residues is similar to that of the starting fragment. We therefore consider
      crystallographic fragment screening to be appropriate for the identification of
      weak but promising fragment hits.

PMID- 25862211
TI  - 1-Heteroaryl-3-phenoxypropan-2-ones as inhibitors of cytosolic phospholipase
      A2alpha and fatty acid amide hydrolase: Effect of the replacement of the ether
      oxygen with sulfur and nitrogen moieties on enzyme inhibition and metabolic
      stability.
AB  - Cytosolic phospholipase A2alpha (cPLA2alpha) and fatty acid amide hydrolase
      (FAAH) are enzymes, which have emerged as attractive targets for the development
      of analgesic and anti-inflammatory drugs. We recently reported that certain 3
      phenoxy-substituted 1-heteroarylpropan-2-ones are inhibitors of cPLA2alpha and/or
      FAAH. Starting from 1-[2-oxo-3-(4-phenoxyphenoxy)propyl]indole-5-carboxylic acid
      (3) and 1-(1H-benzotriazol-1-yl)-3-(4-phenoxyphenoxy)propan-2-one (4), the effect
      of the replacement of the oxygen in position 3 of the propan-2-one scaffold by
      sulfur and nitrogen containing moieties on inhibition of cPLA2alpha and fatty
      acid amide hydrolase as well as on metabolic stability in rat liver S9 fractions
      was investigated. As a result of these structure-activity relationship studies it
      was found that the ether oxygen is of great importance for enzyme inhibitory
      potency. Replacement by sulfur led to an about 100-fold decrease of enzyme
      inhibition, nitrogen and substituted nitrogen atoms at this position even
      resulted in inactivity of the compounds. The effect of the structural variations
      performed on metabolic stability of the important ketone pharmacophore was partly
      different in the two series of compounds. While introduction of SO and SO2
      significantly increased stability of the ketone against reduction in case of the
      indole-5-carboxylic acid 3, it had no effect in case of the benzotriazole 4.
      Further analysis of the metabolism of 3 and 4 in rat liver S9 fractions revealed
      that the major metabolite of 3 was the alcohol 53 formed by reduction of the keto
      group. In contrast, in case of 4 beside keto reduction an excessive hydroxylation
      of the terminal phenoxy group occurred leading to the dihydroxy compound 50.
      Experiments with enzyme inhibitors showed that the phenylhydroxylation of 4 was
      catalyzed by tranylcypromine sensitive cytochrome P450 isoforms, while the
      reduction of the ketone function of 3 and 4 was mainly caused by cytosolic short
      chain dehydrogenases/reductases (cSDR).

PMID- 25862212
TI  - Unfazed or Dazed and Confused: Does Early Adolescent Marijuana Use Cause
      Sustained Impairments in Attention and Academic Functioning?
AB  - There is some suggestion that heavy marijuana use during early adolescence (prior
      to age 17) may cause significant impairments in attention and academic
      functioning that remain despite sustained periods of abstinence. However, no
      longitudinal studies have examined whether both male and female adolescents who
      engage in low (less than once a month) to moderate (at least once a monthly)
      marijuana use experience increased problems with attention and academic
      performance, and whether these problems remain following sustained abstinence.
      The current study used within-individual change models to control for all
      potential pre-existing and time-stable confounds when examining this potential
      causal association in two gender-specific longitudinal samples assessed annually
      from ages 11 to 16 (Pittsburgh Youth Study N = 479; Pittsburgh Girls Study N =
      2296). Analyses also controlled for the potential influence of several pertinent
      time-varying factors (e.g., other substance use, peer delinquency). Prior to
      controlling for time-varying confounds, analyses indicated that adolescents
      tended to experience an increase in parent-reported attention and academic
      problems, relative to their pre-onset levels, during years when they used
      marijuana. After controlling for several time-varying confounds, only the
      association between marijuana use and attention problems in the sample of girls
      remained statistically significant. There was no evidence indicating that
      adolescents who used marijuana experienced lingering attention and academic
      problems, relative to their pre-onset levels, after abstaining from use for at
      least a year. These results suggest that adolescents who engage in low to
      moderate marijuana use experience an increase in observable attention and
      academic problems, but these problems appear to be minimal and are eliminated
      following sustained abstinence. 

PMID- 25862213
TI  - Feedback May Harm: Role of Feedback in Probabilistic Decision Making of
      Adolescents with ADHD.
AB  - Inept probabilistic decision making is commonly associated with ADHD. In
      experimental designs aimed to model probabilistic decision making in ADHD,
      feedback following each choice was, in the majority of studies, part of the
      paradigm. This study examined whether feedback processing plays a role in the
      maladaptive choice behavior of subjects with ADHD by comparing feedback and no
      feedback conditions. Sixty adolescents (49 males), ages 13-18, with and without
      ADHD, performed a descriptive probabilistic choice task in which outcomes and
      probabilities were explicitly provided. Subjects performed the task either with
      or without feedback. Under the no-feedback condition, adolescents with ADHD and
      controls performed similarly, whereas under the feedback condition, subjects with
      ADHD chose the unfavorable outcomes more frequently and risked smaller sums than
      controls. These finding demonstrate the crucial role of feedback in the decision
      making of adolescents with ADHD. 

PMID- 25862214
TI  - Design-Dependent Calculation of the Prosthesis Length in Malleostapedotomy.
AB  - OBJECTIVE: The results of a recently published micro-CT study suggested a
      correlation of the distance between long incus process and stapes footplate and
      the required prosthesis length in malleostapedotomy. The goal of this study was
      to test the reliability of that assumption. METHODS: Rectangular and bent
      prostheses were tested in 11 cadaveric human temporal bone specimens; 1 of them
      showed a stapedial artery. Prosthesis length was calculated based on the distance
      between long incus process and stapes footplate. The rate of acceptable
      prosthesis insertion into the vestibule was investigated. RESULTS: In both
      prostheses designs, the insertion depth into the vestibule did not exceed 1.0 mm.
      Two prostheses did not pass the footplate level in bent prostheses (18%) and 1 in
      rectangular prostheses (9%). CONCLUSION: A rough estimation of the required
      prosthesis length in malleostapedotomy seems possible if the distance between
      long incus process and stapes footplate is known and a design-dependent equation
      exists.

PMID- 25862215
TI  - Lisdexamfetamine Dimesylate Effects on the Pharmacokinetics of Cytochrome P450
      Substrates in Healthy Adults in an Open-Label, Randomized, Crossover Study.
AB  - INTRODUCTION: This open-label, randomized, two-period drug interaction study
      assessed lisdexamfetamine dimesylate (LDX) effects on cytochrome P450 (CYP)
      enzyme (CYP1A2, CYP2D6, CYP2C19, and CYP3A) activity. METHODS: Thirty healthy
      volunteers were administered the Cooperstown cocktail (CYP1A2 [caffeine 200 mg],
      CYP2D6 [dextromethorphan 30 mg], CYP2C19 [omeprazole 40 mg], and CYP3A [midazolam
      0.025 mg/kg] substrates) or Cooperstown cocktail + oral LDX 70 mg. Blood samples
      for pharmacokinetic analysis were collected pre-dose and serially for 72 h post
      dose. Treatment differences in the primary endpoints, maximum plasma
      concentration (C max) and area under the plasma concentration versus time curve
      from 0 to infinity (AUC0-infinity), were assessed using geometric mean ratios
      with 90 % CIs. RESULTS: Geometric least squares (LS) means (without versus with
      LDX) for C max (ng/mL) were 5370 versus 5246 for caffeine, 2.43 versus 2.87 for
      dextromethorphan, 35.23 versus 35.11 for midazolam, and 677.9 versus 466.9 for
      omeprazole; and for AUC0-infinity (ng . h/mL) were 56,207 versus 56,688 for
      caffeine, 34.85 versus 37.27 for dextromethorphan, 92.07 versus 93.04 for
      midazolam, and 1428 versus 1499 for omeprazole. Geometric LS mean ratios were
      within the standard bioequivalence testing range, except for omeprazole and
      dextromethorphan C max. Parent/metabolite C max and AUC0-infinity ratios were
      similar between treatments except for dextromethorphan/dextrorphan AUC0-infinity
      ratio, which was lower with LDX. No serious or severe treatment-emergent adverse
      events were reported. CONCLUSIONS: LDX did not alter CYP1A2, CYP2D6, or CYP3A
      activity. A small C max reduction for omeprazole and its metabolite was observed,
      possibly reflecting an effect either on the activity of CYP2C19 or omeprazole
      absorption.

PMID- 25862216
TI  - Recombinant Activated Factor VII Significantly Reduces Transfusion Requirements
      in Cardiothoracic Surgery.
AB  - BACKGROUND: The off-label use of recombinant activated factor VII (rFVIIa) for
      intractable bleeding is associated with a risk of thrombotic events. The
      objective of this study was to evaluate the incidence and predictors of rFVIIa
      related thrombotic events and its efficacy in the reduction of transfusion
      requirements during various surgeries. METHODS: Ninety-two cases received rFVIIa
      for uncontrollable bleeding despite medical and surgical hemostasis. The
      incidence and risk factors of thrombotic events were analyzed. Blood products
      transfused in the 24 h before and after rFVIIa injection were calculated.
      Subgroup analysis was performed to see which types of surgeries benefited most
      from rFVIIa. RESULTS: The main indication for rFVIIa administration was
      uncontrollable bleeding during cardiothoracic surgery followed by coagulopathy
      due to liver failure followed by neurosurgical procedures. Requirements of blood
      products after rFVIIa decreased significantly by 45 % (p = 0.012), 52 % (p =
      0.0001), and 75 % (p = 0.0001) for red blood cells, plasma, and cryoprecipitate,
      respectively. Subgroup analysis showed that cardiothoracic surgery was the sole
      group that benefited from rFVIIa with a reduction in transfusion of red blood
      cells (p = 0.013), plasma (p = 0.0001), and cryoprecipitate (p = 0.0001).
      Thrombotic events occurred in 9.8 % of the cases mostly on the arterial side (89
      %) and have not contributed to mortality. CONCLUSION: rFVIIa can significantly
      reduce transfusion requirements when given for intractable bleeding during
      cardiothoracic surgery at the expense of thrombotic events in approximately one
      tenth of the cases. Further prospective studies are necessary to study if this
      effect of rFVIIa is translated to a favorable outcome.

PMID- 25862217
TI  - Autologous fat is an efficient hemostatic agent in perforator flap surgery.

PMID- 25862218
TI  - Nasal sequelae of Treacher Collins syndrome.
AB  - OBJECTIVE: This study aimed to determine external and endonasal deformity, and
      satisfaction with nasal functioning and appearance, in Treacher Collins syndrome.
      STUDY DESIGN: A cross-sectional cohort study was conducted. METHODS: Eleven adult
      patients with Treacher Collins syndrome were compared with 151 controls in terms
      of satisfaction with nasal functioning and appearance by means of the Nasal
      Appearance and Function Evaluation Questionnaire. In all patients with Treacher
      Collins syndrome, external nasal deformities were scored on standardized digital
      photographs of the nose as rated independently by three experienced physicians.
      Endonasal deformity was determined by standardized nasal endoscopy. RESULTS: The
      patients were relatively satisfied with the various esthetic nasal subunits. The
      most significant functional problems were snoring (P = 0.001) and quality of
      phonation (P = 0.003). The main external nasal deformities were the dorsal hump
      (73%), external deviation (<=55%), the bifid or bulbous nasal tip (55%), and
      columellar septal luxation (55%). In 82% of the patients, a septal deviation was
      found, often associated with spurs. CONCLUSION: Satisfaction with esthetics of
      the nose was fair, but these patients suffer from the functional problems of
      snoring and impaired quality of phonation. A structured nasal ENT physical
      examination with nasal endoscopy might determine aspects requiring more attention
      during treatment. Septorhinoplasty can be performed at an adult age if there is a
      considerable esthetic wish of the patient and/or nasal obstruction combined with
      septal deviation. Attention should be paid to dorsal hump reduction, correction
      of the deviated external osseous framework, septoplasty, and correction of the
      nasal tip shape. LEVEL OF EVIDENCE: 2b.

PMID- 25862219
TI  - Utilization of D-Lactate as an Energy Source Supports the Growth of Gluconobacter
      oxydans.
AB  - d-Lactate was identified as one of the few available organic acids that supported
      the growth of Gluconobacter oxydans 621H in this study. Interestingly, the strain
      used d-lactate as an energy source but not as a carbon source, unlike other
      lactate-utilizing bacteria. The enzymatic basis for the growth of G. oxydans 621H
      on d-lactate was therefore investigated. Although two putative NAD-independent d
      lactate dehydrogenases, GOX1253 and GOX2071, were capable of oxidizing d-lactate,
      GOX1253 was the only enzyme able to support the d-lactate-driven growth of the
      strain. GOX1253 was characterized as a membrane-bound dehydrogenase with high
      activity toward d-lactate, while GOX2071 was characterized as a soluble oxidase
      with broad substrate specificity toward d-2-hydroxy acids. The latter used
      molecular oxygen as a direct electron acceptor, a feature that has not been
      reported previously in d-lactate-oxidizing enzymes. This study not only clarifies
      the mechanism for the growth of G. oxydans on d-lactate, but also provides new
      insights for applications of the important industrial microbe and the novel d
      lactate oxidase. 

PMID- 25862220
TI  - Validation of Reference Genes for Transcriptional Analyses in Pleurotus ostreatus
      by Using Reverse Transcription-Quantitative PCR.
AB  - Recently, the lignin-degrading basidiomycete Pleurotus ostreatus has become a
      widely used model organism for fungal genomic and transcriptomic analyses. The
      increasing interest in this species has led to an increasing number of studies
      analyzing the transcriptional regulation of multigene families that encode
      extracellular enzymes. Reverse transcription (RT) followed by real-time PCR is
      the most suitable technique for analyzing the expression of gene sets under
      multiple culture conditions. In this work, we tested the suitability of 13
      candidate genes for their use as reference genes in P. ostreatus time course
      cultures for enzyme production. We applied three different statistical algorithms
      and obtained a combination of stable reference genes for optimal normalization of
      RT-quantitative PCR assays. This reference index can be used for future
      transcriptomic analyses and validation of transcriptome sequencing or microarray
      data. Moreover, we analyzed the expression patterns of a laccase and a manganese
      peroxidase (lacc10 and mnp3, respectively) in lignocellulose and glucose-based
      media using submerged, semisolid, and solid-state fermentation. By testing
      different normalization strategies, we demonstrate that the use of nonvalidated
      reference genes as internal controls leads to biased results and
      misinterpretations of the biological responses underlying expression changes. 

PMID- 25862221
TI  - Eight Novel Capsular Polysaccharide Synthesis Gene Loci Identified in Nontypeable
      Streptococcus suis Isolates.
AB  - Streptococcus suis is an important pathogen of pigs and may cause serious disease
      in humans. Serotyping is one of the important diagnostic tools and is used for
      the epidemiological study of S. suis. Nontypeable S. suis strains have been
      reported in many studies; however, the capsular polysaccharide (CPS) synthesis
      cps loci of nontypeable strains have not been analyzed. In this study, we
      investigated the genetic characteristics of cps loci in 78 nontypeable strains
      isolated from healthy pigs. Eight novel cps loci (NCLs) were found, and all of
      them were located between the orfZ-orfX region and the glf gene. All NCLs possess
      the wzy and wzx genes, strongly suggesting that the CPSs of these NCLs were
      synthesized using the Wzx/Wzy-dependent pathway. The cps genes found in the 78
      isolates were assigned to 96 homology groups (HGs), 55 of which were NCL
      specific. The encapsulation of the 78 isolates was also examined using
      transmission electron microscopy. Fifty-three isolates were found to have a
      capsule, and these were of varied thicknesses. Our data enhance our understanding
      of the cps gene cluster diversity of nontypeable S. suis strains and provide
      insight into the evolution of the S. suis capsular genes. 

PMID- 25862222
TI  - Solar and temperature treatments affect the ability of human rotavirus wa to bind
      to host cells and synthesize viral RNA.
AB  - Rotavirus, the leading cause of diarrheal diseases in children under the age of
      five, is often resistant to conventional wastewater treatment and thus can remain
      infectious once released into the aquatic environment. Solar and heat treatments
      can inactivate rotavirus, but it is unknown how these treatments inactivate the
      virus on a molecular level. To answer this question, our approach was to
      correlate rotavirus inactivation with the inhibition of portions of the virus
      life cycle as a means to identify the mechanisms of solar or heat inactivation.
      Specifically, the integrity of the rotavirus NSP3 gene, virus-host cell
      interaction, and viral RNA synthesis were examined after heat (57 degrees C) or
      solar treatment of rotavirus. Only the inhibition of viral RNA synthesis
      positively correlated with a loss of rotavirus infectivity; 57 degrees C
      treatment of rotavirus resulted in a decrease of rotavirus RNA synthesis at the
      same rate as rotavirus infectivity. These data suggest that heat treatment
      neutralized rotaviruses primarily by targeting viral transcription functions. In
      contrast, when using solar disinfection, the decrease in RNA synthesis was
      responsible for approximately one-half of the decrease in infectivity, suggesting
      that other mechanisms, including posttranslational, contribute to inactivation.
      Nevertheless, both solar and heat inactivation of rotaviruses disrupted viral RNA
      synthesis as a mechanism for inactivation. 

PMID- 25862223
TI  - Functional Characterization of Corynebacterium alkanolyticum beta-Xylosidase and
      Xyloside ABC Transporter in Corynebacterium glutamicum.
AB  - The Corynebacterium alkanolyticum xylEFGD gene cluster comprises the xylD gene
      that encodes an intracellular beta-xylosidase next to the xylEFG operon encoding
      a substrate-binding protein and two membrane permease proteins of a xyloside ABC
      transporter. Cloning of the cluster revealed a recombinant beta-xylosidase of
      moderately high activity (turnover for p-nitrophenyl-beta-d-xylopyranoside of 111
      +/- 4 s(-1)), weak alpha-l-arabinofuranosidase activity (turnover for p
      nitrophenyl-alpha-l-arabinofuranoside of 5 +/- 1 s(-1)), and high tolerance to
      product inhibition (Ki for xylose of 67.6 +/- 2.6 mM). Heterologous expression of
      the entire cluster under the control of the strong constitutive tac promoter in
      the Corynebacterium glutamicum xylose-fermenting strain X1 enabled the resultant
      strain X1EFGD to rapidly utilize not only xylooligosaccharides but also arabino
      xylooligosaccharides. The ability to utilize arabino-xylooligosaccharides
      depended on cgR_2369, a gene encoding a multitask ATP-binding protein.
      Heterologous expression of the contiguous xylD gene in strain X1 led to strain
      X1D with 10-fold greater beta-xylosidase activity than strain X1EFGD, albeit with
      a total loss of arabino-xylooligosaccharide utilization ability and only half the
      ability to utilize xylooligosaccharides. The findings suggest some inherent
      ability of C. glutamicum to take up xylooligosaccharides, an ability that is
      enhanced by in the presence of a functional xylEFG-encoded xyloside ABC
      transporter. The finding that xylEFG imparts nonnative ability to take up arabino
      xylooligosaccharides should be useful in constructing industrial strains with
      efficient fermentation of arabinoxylan, a major component of lignocellulosic
      biomass hydrolysates. 

PMID- 25862224
TI  - Steroid hydroxylation by basidiomycete peroxygenases: a combined experimental and
      computational study.
AB  - The goal of this study is the selective oxyfunctionalization of steroids under
      mild and environmentally friendly conditions using fungal enzymes. With this
      purpose, peroxygenases from three basidiomycete species were tested for the
      hydroxylation of a variety of steroidal compounds, using H2O2 as the only
      cosubstrate. Two of them are wild-type enzymes from Agrocybe aegerita and
      Marasmius rotula, and the third one is a recombinant enzyme from Coprinopsis
      cinerea. The enzymatic reactions on free and esterified sterols, steroid
      hydrocarbons, and ketones were monitored by gas chromatography, and the products
      were identified by mass spectrometry. Hydroxylation at the side chain over the
      steroidal rings was preferred, with the 25-hydroxyderivatives predominating.
      Interestingly, antiviral and other biological activities of 25-hydroxycholesterol
      have been reported recently (M. Blanc et al., Immunity 38:106-118, 2013,
      http://dx.doi.org/10.1016/j.immuni.2012.11.004). However, hydroxylation in the
      ring moiety and terminal hydroxylation at the side chain also was observed in
      some steroids, the former favored by the absence of oxygenated groups at C-3 and
      by the presence of conjugated double bonds in the rings. To understand the yield
      and selectivity differences between the different steroids, a computational study
      was performed using Protein Energy Landscape Exploration (PELE) software for
      dynamic ligand diffusion. These simulations showed that the active-site geometry
      and hydrophobicity favors the entrance of the steroid side chain, while the
      entrance of the ring is energetically penalized. Also, a direct correlation
      between the conversion rate and the side chain entrance ratio could be
      established that explains the various reaction yields observed. 

PMID- 25862225
TI  - Symbiosis island shuffling with abundant insertion sequences in the genomes of
      extra-slow-growing strains of soybean bradyrhizobia.
AB  - Extra-slow-growing bradyrhizobia from root nodules of field-grown soybeans harbor
      abundant insertion sequences (ISs) and are termed highly reiterated sequence
      possessing (HRS) strains. We analyzed the genome organization of HRS strains with
      the focus on IS distribution and symbiosis island structure. Using pulsed-field
      gel electrophoresis, we consistently detected several plasmids (0.07 to 0.4 Mb)
      in the HRS strains (NK5, NK6, USDA135, 2281, USDA123, and T2), whereas no
      plasmids were detected in the non-HRS strain USDA110. The chromosomes of the six
      HRS strains (9.7 to 10.7 Mb) were larger than that of USDA110 (9.1 Mb). Using
      MiSeq sequences of 6 HRS and 17 non-HRS strains mapped to the USDA110 genome, we
      found that the copy numbers of ISRj1, ISRj2, ISFK1, IS1632, ISB27, ISBj8, and
      IS1631 were markedly higher in HRS strains. Whole-genome sequencing showed that
      the HRS strain NK6 had four small plasmids (136 to 212 kb) and a large chromosome
      (9,780 kb). Strong colinearity was found between 7.4-Mb core regions of the NK6
      and USDA110 chromosomes. USDA110 symbiosis islands corresponded mainly to five
      small regions (S1 to S5) within two variable regions, V1 (0.8 Mb) and V2 (1.6
      Mb), of the NK6 chromosome. The USDA110 nif gene cluster (nifDKENXSBZHQW-fixBCX)
      was split into two regions, S2 and S3, where ISRj1-mediated rearrangement
      occurred between nifS and nifB. ISs were also scattered in NK6 core regions, and
      ISRj1 insertion often disrupted some genes important for survival and
      environmental responses. These results suggest that HRS strains of soybean
      bradyrhizobia were subjected to IS-mediated symbiosis island shuffling and core
      genome degradation. 

PMID- 25862226
TI  - Real-time PCR and sequencing assays for rapid detection and identification of
      avian schistosomes in environmental samples.
AB  - Cercarial dermatitis, also known as swimmer's itch, is an allergenic skin
      reaction followed by intense itching caused by schistosome cercariae penetrating
      human skin. Cercarial dermatitis outbreaks occur globally and are frequently
      associated with freshwater lakes and are occasionally associated with marine or
      estuarine waters where birds reside year-round or where migratory birds reside.
      In this study, a broadly reactive TaqMan assay targeting 18S rRNA gene (ribosomal
      DNA [rDNA]) sequences that was based on a genetically diverse panel of
      schistosome isolates representing 13 genera and 20 species (the 18S rDNA TaqMan
      assay) was developed. A PCR assay was also developed to amplify a 28S rDNA region
      for subsequent sequencing to identify schistosomes. When applied to surface water
      samples seeded with Schistosoma mansoni cercariae, the 18S rDNA TaqMan assay
      enabled detection at a level of 5 S. mansoni cercariae in 100 liters of lake
      water. The 18S rDNA TaqMan and 28S rDNA PCR sequencing assays were also applied
      to 100-liter water samples collected from lakes in Nebraska and Wisconsin where
      there were reported dermatitis outbreaks. Avian schistosome DNA was detected in
      11 of 34 lake water samples using the TaqMan assay. Further 28S rDNA sequence
      analysis of positive samples confirmed the presence of avian schistosome DNA and
      provided a preliminary identification of the avian schistosomes in 10 of the 11
      samples. These data indicate that the broadly schistosome-reactive TaqMan assay
      can be effective for rapid screening of large-volume water samples for detection
      of avian schistosomes, thereby facilitating timely response actions to mitigate
      or prevent dermatitis outbreaks. Additionally, samples positive by the 18S rDNA
      TaqMan assay can be further assayed using the 28S rDNA sequencing assay to both
      confirm the presence of schistosomes and contribute to their identification. 

PMID- 25862227
TI  - Resistance Genes and Genetic Elements Associated with Antibiotic Resistance in
      Clinical and Commensal Isolates of Streptococcus salivarius.
AB  - The diversity of clinical (n = 92) and oral and digestive commensal (n = 120)
      isolates of Streptococcus salivarius was analyzed by multilocus sequence typing
      (MLST). No clustering of clinical or commensal strains can be observed in the
      phylogenetic tree. Selected strains (92 clinical and 46 commensal strains) were
      then examined for their susceptibilities to tetracyclines, macrolides,
      lincosamides, aminoglycosides, and phenicol antibiotics. The presence of
      resistance genes tet(M), tet(O), erm(A), erm(B), mef(A/E), and catQ and
      associated genetic elements was investigated by PCR, as was the genetic linkage
      of resistance genes. High rates of erythromycin and tetracycline resistance were
      observed among the strains. Clinical strains displayed either the erm(B)
      (macrolide-lincosamide-streptogramin B [MLSB] phenotype) or mef(A/E) (M
      phenotype) resistance determinant, whereas almost all the commensal strains
      harbored the mef(A/E) resistance gene, carried by a macrolide efflux genetic
      assembly (MEGA) element. A genetic linkage between a macrolide resistance gene
      and genes of Tn916 was detected in 23 clinical strains and 5 commensal strains,
      with a predominance of Tn3872 elements (n = 13), followed by Tn6002 (n = 11) and
      Tn2009 (n = 4) elements. Four strains harboring a mef(A/E) gene were also
      resistant to chloramphenicol and carried a catQ gene. Sequencing of the genome of
      one of these strains revealed that these genes colocalized on an IQ-like element,
      as already described for other viridans group streptococci. ICESt3-related
      elements were also detected in half of the isolates. This work highlights the
      potential role of S. salivarius in the spread of antibiotic resistance genes both
      in the oral sphere and in the gut. 

PMID- 25862229
TI  - Abundance and distribution of dimethylsulfoniopropionate degradation genes and
      the corresponding bacterial community structure at dimethyl sulfide hot spots in
      the tropical and subtropical pacific ocean.
AB  - Dimethylsulfoniopropionate (DMSP) is mainly produced by marine phytoplankton but
      is released into the microbial food web and degraded by marine bacteria to
      dimethyl sulfide (DMS) and other products. To reveal the abundance and
      distribution of bacterial DMSP degradation genes and the corresponding bacterial
      communities in relation to DMS and DMSP concentrations in seawater, we collected
      surface seawater samples from DMS hot spot sites during a cruise across the
      Pacific Ocean. We analyzed the genes encoding DMSP lyase (dddP) and DMSP
      demethylase (dmdA), which are responsible for the transformation of DMSP to DMS
      and DMSP assimilation, respectively. The averaged abundance (+/-standard
      deviation) of these DMSP degradation genes relative to that of the 16S rRNA genes
      was 33% +/- 12%. The abundances of these genes showed large spatial variations.
      dddP genes showed more variation in abundances than dmdA genes. Multidimensional
      analysis based on the abundances of DMSP degradation genes and environmental
      factors revealed that the distribution pattern of these genes was influenced by
      chlorophyll a concentrations and temperatures. dddP genes, dmdA subclade C/2
      genes, and dmdA subclade D genes exhibited significant correlations with the
      marine Roseobacter clade, SAR11 subgroup Ib, and SAR11 subgroup Ia, respectively.
      SAR11 subgroups Ia and Ib, which possessed dmdA genes, were suggested to be the
      main potential DMSP consumers. The Roseobacter clade members possessing dddP
      genes in oligotrophic subtropical regions were possible DMS producers. These
      results suggest that DMSP degradation genes are abundant and widely distributed
      in the surface seawater and that the marine bacteria possessing these genes
      influence the degradation of DMSP and regulate the emissions of DMS in
      subtropical gyres of the Pacific Ocean. 

PMID- 25862228
TI  - Structure and Mechanism of Ferulic Acid Decarboxylase (FDC1) from Saccharomyces
      cerevisiae.
AB  - The nonoxidative decarboxylation of aromatic acids occurs in a range of microbes
      and is of interest for bioprocessing and metabolic engineering. Although phenolic
      acid decarboxylases provide useful tools for bioindustrial applications, the
      molecular bases for how these enzymes function are only beginning to be examined.
      Here we present the 2.35-A-resolution X-ray crystal structure of the ferulic acid
      decarboxylase (FDC1; UbiD) from Saccharomyces cerevisiae. FDC1 shares structural
      similarity with the UbiD family of enzymes that are involved in ubiquinone
      biosynthesis. The position of 4-vinylphenol, the product of p-coumaric acid
      decarboxylation, in the structure identifies a large hydrophobic cavity as the
      active site. Differences in the beta2e-alpha5 loop of chains in the crystal
      structure suggest that the conformational flexibility of this loop allows access
      to the active site. The structure also implicates Glu285 as the general base in
      the nonoxidative decarboxylation reaction catalyzed by FDC1. Biochemical analysis
      showed a loss of enzymatic activity in the E285A mutant. Modeling of 3-methoxy-4
      hydroxy-5-decaprenylbenzoate, a partial structure of the physiological UbiD
      substrate, in the binding site suggests that an ~30-A-long pocket adjacent to the
      catalytic site may accommodate the isoprenoid tail of the substrate needed for
      ubiquinone biosynthesis in yeast. The three-dimensional structure of yeast FDC1
      provides a template for guiding protein engineering studies aimed at optimizing
      the efficiency of aromatic acid decarboxylation reactions in bioindustrial
      applications. 

PMID- 25862230
TI  - Long-Term Fungal Inhibition by Pisum sativum Flour Hydrolysate during Storage of
      Wheat Flour Bread.
AB  - In order to identify antifungal compounds from natural sources to be used as
      ingredients in the bakery industry, water/salt-soluble extracts (WSE) from
      different legume flour hydrolysates obtained by the use of a fungal protease were
      assayed against Penicillium roqueforti DPPMAF1. The agar diffusion assays allowed
      the selection of the pea (Pisum sativum) hydrolysate as the most active. As shown
      by the hyphal radial growth rate, the WSE had inhibitory activity towards several
      fungi isolated from bakeries. The MIC of the WSE was 9.0 mg/ml. Fungal inhibition
      was slightly affected by heating and variations in pH. The antifungal activity
      was attributed to three native proteins (pea defensins 1 and 2 and a nonspecific
      lipid transfer protein [nsLTP]) and a mixture of peptides released during
      hydrolysis. The three proteins have been reported previously as components of the
      defense system of the plant. Five peptides were purified from WSE and were
      identified as sequences encrypted in leginsulin A, vicilin, provicilin, and the
      nsLTP. To confirm antifungal activity, the peptides were chemically synthesized
      and tested. Freeze-dried WSE were used as ingredients in leavened baked goods. In
      particular, breads made by the addition of 1.6% (wt/wt) of the extract and
      fermented by baker's yeast or sourdough were characterized for their main
      chemical, structural, and sensory features, packed in polyethylene bags, stored
      at room temperature, and compared to controls prepared without pea hydrolysate.
      Artificially inoculated slices of a bread containing the WSE did not show
      contamination by fungi until at least 21 days of storage and behaved like the
      bread prepared with calcium propionate (0.3%, wt/wt). 

PMID- 25862231
TI  - Dynamic Succession of Groundwater Functional Microbial Communities in Response to
      Emulsified Vegetable Oil Amendment during Sustained In Situ U(VI) Reduction.
AB  - A pilot-scale field experiment demonstrated that a one-time amendment of
      emulsified vegetable oil (EVO) reduced groundwater U(VI) concentrations for 1
      year in a fast-flowing aquifer. However, little is known about how EVO amendment
      stimulates the functional gene composition, structure, and dynamics of
      groundwater microbial communities toward prolonged U(VI) reduction. In this
      study, we hypothesized that EVO amendment would shift the functional gene
      composition and structure of groundwater microbial communities and stimulate key
      functional genes/groups involved in EVO biodegradation and reduction of electron
      acceptors in the aquifer. To test these hypotheses, groundwater microbial
      communities after EVO amendment were analyzed using a comprehensive functional
      gene microarray. Our results showed that EVO amendment stimulated sequential
      shifts in the functional composition and structure of groundwater microbial
      communities. Particularly, the relative abundance of key functional genes/groups
      involved in EVO biodegradation and the reduction of NO3 (-), Mn(IV), Fe(III),
      U(VI), and SO4 (2-) significantly increased, especially during the active U(VI)
      reduction period. The relative abundance for some of these key functional
      genes/groups remained elevated over 9 months. Montel tests suggested that the
      dynamics in the abundance, composition, and structure of these key functional
      genes/groups were significantly correlated with groundwater concentrations of
      acetate, NO3 (-), Mn(II), Fe(II), U(VI), and SO4 (2-). Our results suggest that
      EVO amendment stimulated dynamic succession of key functional microbial
      communities. This study improves our understanding of the composition, structure,
      and function changes needed for groundwater microbial communities to sustain a
      long-term U(VI) reduction. 

PMID- 25862232
TI  - Genetic Diversity of the fliC Genes Encoding the Flagellar Antigen H19 of
      Escherichia coli and Application to the Specific Identification of
      Enterohemorrhagic E. coli O121:H19.
AB  - Enterohemorrhagic Escherichia coli (EHEC) O121:H19 belong to a specific clonal
      type distinct from other classical EHEC and major enteropathogenic E. coli groups
      and is regarded as one of the major EHEC serogroups involved in severe infections
      in humans. Sequencing of the fliC genes associated with the flagellar antigen H19
      (fliCH19) revealed the genetic diversity of the fliCH19 gene sequences in E.
      coli. A cluster analysis of 12 fliCH19 sequences, 4 from O121 and 8 from non-O121
      E. coli strains, revealed five different genotypes. All O121:H19 strains fell
      into one cluster, whereas a second cluster was formed by five non-O121:H19
      strains. Cluster 1 and cluster 2 strains differ by 27 single nucleotide exchanges
      in their fliCH19 genes (98.5% homology). Based on allele discrimination of the
      fliCH19 genes, a real-time PCR test was designed for specific identification of
      EHEC O121:H19. The O121 fliCH19 PCR tested negative in 73 E. coli H19 strains
      that belonged to serogroups other than O121, including 28 different O groups, O
      nontypeable H19, and O-rough:H19 strains. The O121 fliCH19 PCR reacted with all
      16 tested O121:H19 strains and 1 O-rough:H19 strain which was positive for the
      O121 wzx gene. A cross-reaction was observed only with E. coli H32 strains which
      share sequence similarities in the target region of the O121 fliCH19 PCR. The
      combined use of O-antigen genotyping (O121 wzx) and the detection of O121 fliCH19
      allele type contributes to improving the identification and molecular serotyping
      of EHEC O121:H19 motile and nonmotile strains and variants of these strains
      lacking stx genes. 

PMID- 25862233
TI  - Mechanically Ventilated, Cardiothoracic Surgical Patients Have Significantly
      Different Energy Requirements Comparing Indirect Calorimetry and the Penn State
      Equations.
AB  - BACKGROUND: Nutrition equations have been validated with indirect calorimetry for
      determining energy needs in intensive care unit (ICU) populations. This study
      tested the hypothesis that mechanically ventilated cardiothoracic surgical
      patients would have significantly different energy requirements when determined
      by indirect calorimetry vs the Penn State equations. MATERIALS AND METHODS: This
      single-center, retrospective cohort analysis of consecutive cardiothoracic
      surgical patients adhered to a prospectively designed protocol for indirect
      calorimetry energy measurements. Energy needs were estimated by Penn State
      equations 2010 and 2003b and then indirect calorimetry. RESULTS: Analyzed
      patients (n = 71) had a mean +/- SD difference of 556 +/- 543 calories/d between
      indirect calorimetry and Penn State formulae, as well as a mean +/- SD percentage
      caloric difference of 32% +/- 31% (95% confidence interval [CI], -20 to 87) with
      a range of 1311 calories (minimum difference, -379; maximum difference, 933).
      There was a 10% or greater difference in resting metabolic rate between indirect
      calorimetry and the Penn State equations in 89% of patients (95% CI, 79%-95%).
      Based on Lin's concordance correlation of 0.20 (95% CI, 0.09-0.32), the strength
      of agreement between the resting metabolic rates determined by indirect
      calorimetry compared with the Penn State equations was poor within this patient
      sample. Indirect calorimetry performance showed a 10% increase in caloric need in
      77% of patients and was associated with a nutrition prescription change in 66%.
      CONCLUSIONS: Mechanically ventilated cardiothoracic surgical ICU patients appear
      to have higher energy requirements by indirect calorimetry than those determined
      by Penn State equations. Future studies targeting indirect calorimetry in
      relation to clinical outcomes are needed.

PMID- 25862234
TI  - Salvage therapy with gemcitabine, vinorelbine, and pegylated liposomal
      doxorubicin for relapsed or refractory pediatric Hodgkin lymphoma. Results of a
      retrospective series of four children.
AB  - While the vast majority of pediatric Hodgkin lymphoma (HL) is curable, the
      prognosis of early relapses and refractory diseases remains poor. Recently, the
      combination of gemcitabine, vinorelbine, and pegylated liposomal doxorubicin
      (GVD) displayed encouraging results on adults with relapsed/refractory diseases.
      Here, we retrospectively report the results of the GVD salvage regimen on four
      pediatric patients of our ward with a heavily pretreated relapsed/refractory HL.
      Three of them had nodular sclerosis subtype. They achieved a complete remission
      after two, three, or four courses of GVD and received high-dose chemotherapy
      followed by a stem-cell transplantation (auto-auto, auto-allo, and auto). They
      have been in sustained remission respectively for almost 2, 4, and 5 years. The
      fourth patient had a lymphocyte-depleted subtype which was initially diagnosed as
      anaplastic large cell lymphoma. After four courses of GVD, his disease stabilized
      then progressed again. In total, 15 cycles of GVD were applied to the patients.
      The toxicity of each course of GVD was mainly hematologic. No cardiotoxicity
      occurred despite a prior exposure to anthracyclines and radiotherapy. Thus, the
      GVD combination seems to be an effective pre-transplant rescue treatment for
      pediatric patients.

PMID- 25862235
TI  - Outcomes of mismatched and unrelated donor hematopoietic stem cell
      transplantation in Fanconi anemia conditioned with chemotherapy only.
AB  - Fanconi anemia (FA) is a genomic instability syndrome associated with bone marrow
      failure, myelodysplastic syndrome (MDS), and/or acute myeloid leukemia (AML)
      requiring hematopoietic stem cell transplantation (HSCT) to restore normal
      hematopoiesis. Although low-intensity fludarabine-based preparative regimens
      without radiation confer excellent outcomes in FA HSCTs with HLA-matched sibling
      donors, outcomes for FA patients with alternative donors are less encouraging,
      albeit improving. We present our experience with 17 FA patients who completed
      mismatched related or unrelated donor HSCT using a non-radiation fludarabine
      based preparative regimen at Charite University Medicine Berlin. All patients
      engrafted; however, one patient had unstable chimerism in the setting of multi
      viral infections that necessitated a stem cell boost to revert to full donor
      chimerism. Forty-seven percent of patients developed grade I acute graft-verus
      host disease (aGVHD). No grade II-IV aGVHD or chronic graft-versus-host disease
      of any severity occurred. At a median follow-up of 30 months, 88 % of patients
      are alive with normal hematopoiesis. Two patients died of infections 4 months
      post-transplantation. These results demonstrate that short-term outcomes for FA
      patients with mismatched and unrelated donor HSCTs can be excellent using
      chemotherapy only conditioning. Viral reactivation, however, was a major
      treatment-related complication.

PMID- 25862236
TI  - Re: Editorial Comment on Randomized and Double-Blinded Clinical Trial of the
      Safety and Calcium Kidney Stone Dissolving Efficacy of Lapis Judaicus: D. G.
      Assimos J Urol 2015;193:897-898.

PMID- 25862238
TI  - Extreme hypernatremia (254 mmol/L) and electrocardiogram findings.

PMID- 25862237
TI  - Efficacy and safety of combining pentoxifylline with angiotensin-converting
      enzyme inhibitor or angiotensin II receptor blocker in diabetic nephropathy: a
      meta-analysis.
AB  - OBJECTIVE: Pentoxifylline (PTF) has anti-inflammatory properties, which may be
      beneficial for diabetic nephropathy (DN). A meta-analysis was conducted to assess
      the additive effect of pentoxifylline and its safety among patients with type 2
      DN under blockade of angiotensin system. DATA SOURCES: Relevant studies were
      searched from PubMed, CBM, EMBASE, CENTRAL and Cochrane renal group specialized
      register. SELECTION CRITERIA: All RCTs that compared the benefits and harms of
      pentoxifylline and ACEI/ARB with ACEI/ARB alone for DN were included. DATA
      EXTRACTION AND ANALYSIS: Pertinent data were extracted independently by two
      authors. Meta-analyses were performed when more than one study provided data on a
      comparable outcome. Standard mean differences (SMDs) for proteinuria and
      albuminuria, mean differences (MDs) for systolic blood pressure (SBP), diastolic
      blood pressure (DBP), HbA1c, serum creatinine (Scr), creatinine clearance (CrCl)
      and urine tumor necrosis factor-alpha (UTNF-alpha), 95% confidence intervals
      (CIs) were calculated, and heterogeneity was assessed with the I (2) test.
      Adverse effects were assessed using descriptive techniques. RESULTS: Eight
      studies including 587 patients with a median duration of 5 months were
      identified. Compared with ACEI/ARB alone, the combination of PTF and ACEI/ARB
      significantly reduced proteinuria (SMD 0.76, 95% CI 0.52-0.99), albuminuria (SMD
      0.36, 95% CI 0.12-0.59) and UTNF-alpha (MD 1.56 ng/g, 95% CI 0.09-3.03). However,
      no statistically significant changes were observed for SBP, DBP, HbA1c, Scr and
      CrCl. The most frequent adverse effects in patients treated with PTF were
      gastrointestinal symptoms (28/298) and dizziness (7/298), but in most cases,
      these symptoms were mild, only six participants withdrew due to intractable
      nausea and vomiting. CONCLUSIONS: Pentoxifylline can significantly provide
      additive antiproteinuric effect independent from the decrease in BP or
      improvement in glycemic control in DN patients under blockade of angiotensin
      system. Further large, multicenter, high-quality studies with long duration are
      necessary to prove whether it really has renoprotective effects in this patient
      population.

PMID- 25862239
TI  - Can we compare serum sclerostin results obtained with different assays in
      hemodialysis patients?
AB  - PURPOSE: Sclerostin, secreted by osteocytes, plays a key role in antagonizing
      bone formation. Recent studies, which seldom include chronic kidney disease (CKD)
      patients, have reported on the association of sclerostin and mortality, with
      contradictory results. The assay-linked variability may contribute to these
      discrepant results. METHODS: We have compared sclerostin results obtained with
      two assays (TECO and Biomedica) in a cohort of 91 CKD patients undergoing
      hemodialysis. RESULTS: We found a strong correlation (r = 0.870, p < 0.0001)
      between the serum sclerostin concentrations measured by the two assays. Bland
      Altman plot shows that, although there was a partial agreement between the
      assays, differences found for individual values (-0.27 +/- 0.54; ranging from 
      1.3 to 0.8 ng/ml) were quite unpredictable. By using TECO, there was a
      significant relationship between serum sclerostin, and calcitonin (r = 0.224), IL
      6 (r = 0.251) and FGF23 (r = 0.331) levels while no correlation was found with
      PTH or total alkaline phosphatase. Regarding Biomedica, there was a significant
      correlation with calcitonin (r = 0.260), and beta2 microglobulin (r = 0.210), but
      no correlation with PTH or total alkaline phosphatase. Overall, 25.3% among the
      patients had different classifications as to normal or high values, according to
      the manufacturer. CONCLUSION: Sclerostin levels should be interpreted with
      caution, as they can vary widely according to the assay used. Further studies are
      clearly needed before considering sclerostin as a true marker of mortality.
      Moreover, we do not know at present which serum sclerostin levels should be
      regarded as either normal or potentially dangerous in patients with CKD.

PMID- 25862240
TI  - Predictors for de novo stress urinary incontinence following extensive pelvic
      reconstructive surgery.
AB  - INTRODUCTION AND HYPOTHESIS: The aim of this study was to look for possible
      predictors preoperatively for the development of de novo stress urinary
      incontinence (SUI) in urodynamically continent women who underwent pelvic
      reconstructive surgery (PRS). MATERIALS AND METHODS: Medical records of 637
      continent women who underwent PRS for severe prolapse from January 2005 to
      December 2013 in our institutions were included in this study. We excluded women
      who had urodynamic stress incontinence (UDI) either occult or overt, detrusor
      overactivity, neurogenic bladder-voiding dysfunction, and previous anti
      incontinent surgery. Primary outcome measure was the development of de novo SUI
      at 6 months to 1 year post operation. RESULTS: Of women in this study, 11 %
      developed postoperative de novo SUI at 6 months to 1 year of follow-up. Women
      older than 66 years were 2.86 times [95 % confidence interval (CI) 1.01-2.53, p =
      0.14], diabetes mellitus (DM) 2.18 times (95 % CI 1.63-4.21, p = 0.002), certain
      type of transvaginal mesh procedure 3.5 times (95 % CI, p < 0.001), maximum
      urethral closure pressure (MUCP) < 60 mmH20 4.65 times (95 % CI, 2.87-8.64, p <
      0.001), and functional urethral length (FUL) < 2 cm 3.48 times (95 % CI, 2.13
      5.83, p < 0.001) at greater risk of developing de novo SUI. CONCLUSIONS:
      Continent women with advanced pelvic organ prolapse (POP) > 66 years, with DM or
      low MUCP and FUL values during preoperative urodynamic evaluation have higher
      risk of developing de novo SUI; therefore, we suggest counselling such women for
      concomitant PRS and anti-incontinent surgery.

PMID- 25862241
TI  - One-year prospective comparison of vaginal pessaries and surgery for pelvic organ
      prolapse using the validated ICIQ-VS and ICIQ-UI (SF) questionnaires.
AB  - INTRODUCTION AND HYPOTHESIS: Vaginal pessaries, pelvic floor exercises and
      surgery are treatment options for women with symptomatic pelvic organ prolapse
      (POP). The aim of this study was to compare the outcomes of pessaries and surgery
      in women with symptomatic POP using the validated International Consultation on
      Incontinence Questionnaire-Vaginal Symptoms (ICIQ-VS) and Urinary Incontinence
      (ICIQ-UI) Short Form (SF). METHODS: Women attending the Urogynecology clinics
      with symptomatic POP were recruited. All women were treated using either a
      vaginal pessary or surgery. Outcomes were evaluated and then compared at 1 year
      using the validated ICIQ-VS and ICIQ-UI (SF) questionnaires. RESULTS: A total of
      287 women with symptomatic prolapse were recruited. 269 women completed the
      questionnaires at baseline and 183 at 1 year. At 1 year, improvement was noted in
      quality of life (QOL), frequency of urinary leak and vaginal symptoms in both
      groups except for the symptom of vaginal soreness in the pessary group and the
      symptom of a tight vagina in the surgery group. However, both these symptoms were
      not bothersome. Women who underwent surgery demonstrated an improvement in faecal
      evacuation and sex life. There was an overall statistically significant
      improvement in vaginal, sex, QOL and urinary symptom scores in both groups. No
      statistically significant difference was noted between the surgery and the
      pessary groups. CONCLUSIONS: Using validated questionnaires 1 year after
      treatment, women with symptomatic POP report improvement in vaginal, bowel,
      urinary and quality of life scores when treated with either pessary use or
      surgery. No statistically significant difference was noted in the two groups.

PMID- 25862242
TI  - oskar RNA plays multiple noncoding roles to support oogenesis and maintain
      integrity of the germline/soma distinction.
AB  - The Drosophila oskar (osk) mRNA is unusual in that it has both coding and
      noncoding functions. As an mRNA, osk encodes a protein required for embryonic
      patterning and germ cell formation. Independent of that function, the absence of
      osk mRNA disrupts formation of the karyosome and blocks progression through
      oogenesis. Here we show that loss of osk mRNA also affects the distribution of
      regulatory proteins, relaxing their association with large RNPs within the
      germline, and allowing them to accumulate in the somatic follicle cells. This and
      other noncoding functions of the osk mRNA are mediated by multiple sequence
      elements with distinct roles. One role, provided by numerous binding sites in two
      distinct regions of the osk 3' UTR, is to sequester the translational regulator
      Bruno (Bru), which itself controls translation of osk mRNA. This defines a novel
      regulatory circuit, with Bru restricting the activity of osk, and osk in turn
      restricting the activity of Bru. Other functional elements, which do not bind Bru
      and are positioned close to the 3' end of the RNA, act in the oocyte and are
      essential. Despite the different roles played by the different types of elements
      contributing to RNA function, mutation of any leads to accumulation of the
      germline regulatory factors in the follicle cells. 

PMID- 25862243
TI  - Balneotherapy (or spa therapy) for rheumatoid arthritis.
AB  - BACKGROUND: No cure for rheumatoid arthritis (RA) is known at present, so
      treatment often focuses on management of symptoms such as pain, stiffness and
      mobility. Treatment options include pharmacological interventions, physical
      therapy treatments and balneotherapy. Balneotherapy is defined as bathing in
      natural mineral or thermal waters (e.g. mineral baths, sulphur baths, Dead Sea
      baths), using mudpacks or doing both. Despite its popularity, reported scientific
      evidence for the effectiveness or efficacy of balneotherapy is sparse. This
      review, which evaluates the effects of balneotherapy in patients with RA, is an
      update of a Cochrane review first published in 2003 and updated in 2008.
      OBJECTIVES: To perform a systematic review on the benefits and harms of
      balneotherapy in patients with RA in terms of pain, improvement, disability,
      tender joints, swollen joints and adverse events. SEARCH METHODS: We searched the
      Cochrane 'Rehabilitation and Related Therapies' Field Register (to December
      2014), the Cochrane Central Register of Controlled Trials (2014, Issue 1),
      MEDLIINE (1950 to December 2014), EMBASE (1988 to December 2014), the Cumulative
      Index to Nursing and Allied Health Literature (CINAHL) (1982 to December 2014),
      the Allied and Complementary Medicine Database (AMED) (1985 to December 2014),
      PsycINFO (1806 to December 2014) and the Physiotherapy Evidence Database (PEDro).
      We applied no language restrictions; however, studies not reported in English,
      Dutch, Danish, Swedish, Norwegian, German or French are awaiting assessment. We
      also searched the World Health Organization (WHO) International Clinical Trials
      Registry Platform for ongoing and recently completed trials. SELECTION CRITERIA:
      Studies were eligible if they were randomised controlled trials (RCTs) consisting
      of participants with definitive or classical RA as defined by the American
      Rheumatism Association (ARA) criteria of 1958, the ARA/American College of
      Rheumatology (ACR) criteria of 1988 or the ACR/European League Against Rheumatism
      (EULAR) criteria of 2010, or by studies using the criteria of
      Steinbrocker.Balneotherapy had to be the intervention under study, and had to be
      compared with another intervention or with no intervention.The World Health
      Organization (WHO) and the International League Against Rheumatism (ILAR)
      determined in 1992 a core set of eight endpoints in clinical trials concerning
      patients with RA. We considered pain, improvement, disability, tender joints,
      swollen joints and adverse events among the main outcome measures. We excluded
      studies when only laboratory variables were reported as outcome measures. DATA
      COLLECTION AND ANALYSIS: Two review authors independently selected trials,
      performed data extraction and assessed risk of bias. We resolved disagreements by
      consensus and, if necessary, by third party adjudication. MAIN RESULTS: This
      review includes two new studies and a total of nine studies involving 579
      participants. Unfortunately, most studies showed an unclear risk of bias in most
      domains. Four out of nine studies did not contribute to the analysis, as they
      presented no data.One study involving 45 participants with hand RA compared
      mudpacks versus placebo. We found no statistically significant differences in
      terms of pain on a 0 to 100-mm visual analogue scale (VAS) (mean difference (MD)
      0.50, 95% confidence interval (CI) -0.84 to 1.84), improvement (risk ratio (RR)
      0.96, 95% CI 0.54 to 1.70) or number of swollen joints on a scale from 0 to 28
      (MD 0.60, 95% CI -0.90 to 2.10) (very low level of evidence). We found a very low
      level of evidence of reduction in the number of tender joints on a scale from 0
      to 28 (MD -4.60, 95% CI -8.72 to -0.48; 16% absolute difference). We reported no
      physical disability and presented no data on withdrawals due to adverse events or
      on serious adverse events.Two studies involving 194 participants with RA
      evaluated the effectiveness of additional radon in carbon dioxide baths. We found
      no statistically significant differences between groups for all outcomes at three
      month follow-up (low to moderate level of evidence). We noted some benefit of
      additional radon at six months in terms of pain frequency (RR 0.6, 95% CI 0.4 to
      0.9; 31% reduction; improvement in one or more points (categories) on a 4-point
      scale; moderate level of evidence) and 9.6% reduction in pain intensity on a 0 to
      100-mm VAS (MD 9.6 mm, 95% CI 1.6 to 17.6; moderate level of evidence). We also
      observed some benefit in one study including 60 participants in terms of
      improvement in one or more categories based on a 4-point scale (RR 2.3, 95% CI
      1.1 to 4.7; 30% absolute difference; low level of evidence). Study authors did
      not report physical disability, tender joints, swollen joints, withdrawals due to
      adverse events or serious adverse events.One study involving 148 participants
      with RA compared balneotherapy (seated immersion) versus hydrotherapy (exercises
      in water), land exercises or relaxation therapy. We found no statistically
      significant differences in pain on the McGill Questionnaire or in physical
      disability (very low level of evidence) between balneotherapy and the other
      interventions. No data on improvement, tender joints, swollen joints, withdrawals
      due to adverse events or serious adverse events were presented.One study
      involving 57 participants with RA evaluated the effectiveness of mineral baths
      (balneotherapy) versus Cyclosporin A. We found no statistically significant
      differences in pain intensity on a 0 to 100-mm VAS (MD 9.64, 95% CI -1.66 to
      20.94; low level of evidence) at 8 weeks (absolute difference 10%). We found some
      benefit of balneotherapy in overall improvement on a 5-point scale at eight weeks
      of 54% (RR 2.35, 95% CI 1.44 to 3.83). We found no statistically significant
      differences (low level of evidence) in the number of swollen joints, but some
      benefit of Cyclosporin A in the number of tender joints (MD 8.9, 95% CI 3.8 to
      14; very low level of evidence). Physical disability, withdrawals due to adverse
      events and serious adverse events were not reported. AUTHORS' CONCLUSIONS:
      Overall evidence is insufficient to show that balneotherapy is more effective
      than no treatment, that one type of bath is more effective than another or that
      one type of bath is more effective than mudpacks, exercise or relaxation therapy.

PMID- 25862244
TI  - Divergent selection along climatic gradients in a rare central European endemic
      species, Saxifraga sponhemica.
AB  - BACKGROUND AND AIMS: The effects of habitat fragmentation on quantitative genetic
      variation in plant populations are still poorly known. Saxifraga sponhemica is a
      rare endemic of Central Europe with a disjunct distribution, and a stable and
      specialized habitat of treeless screes and cliffs. This study therefore used S.
      sponhemica as a model species to compare quantitative and molecular variation in
      order to explore (1) the relative importance of drift and selection in shaping
      the distribution of quantitative genetic variation along climatic gradients; (2)
      the relationship between plant fitness, quantitative genetic variation, molecular
      genetic variation and population size; and (3) the relationship between the
      differentiation of a trait among populations and its evolvability. METHODS:
      Genetic variation within and among 22 populations from the whole distribution
      area of S. sponhemica was studied using RAPD (random amplified polymorphic DNA)
      markers, and climatic variables were obtained for each site. Seeds were collected
      from each population and germinated, and seedlings were transplanted into a
      common garden for determination of variation in plant traits. KEY RESULTS: In
      contrast to previous results from rare plant species, strong evidence was found
      for divergent selection. Most population trait means of S. sponhemica were
      significantly related to climate gradients, indicating adaptation. Quantitative
      genetic differentiation increased with geographical distance, even when neutral
      molecular divergence was controlled for, and QST exceeded FST for some traits.
      The evolvability of traits was negatively correlated with the degree of
      differentiation among populations (QST), i.e. traits under strong selection
      showed little genetic variation within populations. The evolutionary potential of
      a population was not related to its size, the performance of the population or
      its neutral genetic diversity. However, performance in the common garden was
      lower for plants from populations with reduced molecular genetic variation,
      suggesting inbreeding depression due to genetic erosion. CONCLUSIONS: The
      findings suggest that studies of molecular and quantitative genetic variation may
      provide complementary insights important for the conservation of rare species.
      The strong differentiation of quantitative traits among populations shows that
      selection can be an important force for structuring variation in evolutionarily
      important traits even for rare endemic species restricted to very specific
      habitats.

PMID- 25862245
TI  - Dock10, a Cdc42 and Rac1 GEF, induces loss of elongation, filopodia, and ruffles
      in cervical cancer epithelial HeLa cells.
AB  - Dock10 is one of the three members of the Dock-D family of Dock proteins, a class
      of guanine nucleotide exchange factors (GEFs) for Rho GTPases. Its homologs Dock9
      and Dock11 are Cdc42 GEFs. Dock10 is required for maintenance of rounded
      morphology and amoeboid-type movement. Full-length isoforms of Dock10 have been
      recently cloned. Here, we address GTPase specificity and GEF activity of Dock10.
      In order of decreasing intensity, Dock10 interacted with nucleotide-free Rac1,
      Cdc42, and Rac3, and more weakly with Rac2, RhoF, and RhoG. Inducible expression
      of Dock10 in HeLa epithelial cells promoted GEF activity on Cdc42 and Rac1, and a
      morphologic change in two-dimensional culture consisting in loss of cell
      elongation, increase of filopodia, and ruffles. Area in contact with the
      substrate of cells that spread with non-elongated morphology was larger in cells
      expressing Dock10. Inducible expression of constitutively active mutants of Cdc42
      and Rac1 in HeLa cells also induced loss of elongation. However, Cdc42 induced
      filopodia and contraction, and Rac1 induced membrane ruffles and flattening. When
      co-expressed with Dock10, Cdc42 potentiated filopodia, and Rac1 potentiated
      ruffles. These results suggest that Dock10 functions as a dual GEF for Cdc42 and
      Rac1, affecting cell morphology, spreading and actin cytoskeleton protrusions of
      adherent HeLa cells. 

PMID- 25862246
TI  - Loss of a Clueless-dGRASP complex results in ER stress and blocks Integrin exit
      from the perinuclear endoplasmic reticulum in Drosophila larval muscle.
AB  - Drosophila Clueless (Clu) and its conserved orthologs are known for their role in
      the prevention of mitochondrial clustering. Here, we uncover a new role for Clu
      in the delivery of integrin subunits in muscle tissue. In clu mutants, alphaPS2
      integrin, but not betaPS integrin, abnormally accumulates in a perinuclear
      endoplasmic reticulum (ER) subdomain, a site that mirrors the endogenous
      localization of Clu. Loss of components essential for mitochondrial distribution
      do not phenocopy the clu mutant alphaPS2 phenotype. Conversely, RNAi knockdown of
      the Drosophila Golgi reassembly and stacking protein GRASP55/65 (dGRASP)
      recapitulates clu defects, including the abnormal accumulation of alphaPS2 and
      larval locomotor activity. Both Clu and dGRASP proteins physically interact and
      loss of Clu displaces dGRASP from ER exit sites, suggesting that Clu cooperates
      with dGRASP for the exit of alphaPS2 from a perinuclear subdomain in the ER. We
      also found that Clu and dGRASP loss of function leads to ER stress and that the
      stability of the ER exit site protein Sec16 is severely compromised in the clu
      mutants, thus explaining the ER accumulation of alphaPS2. Remarkably, exposure of
      clu RNAi larvae to chemical chaperones restores both alphaPS2 delivery and
      functional ER exit sites. We propose that Clu together with dGRASP prevents ER
      stress and therefore maintains Sec16 stability essential for the functional
      organization of perinuclear early secretory pathway. This, in turn, is essential
      for integrin subunit alphaPS2 ER exit in Drosophila larval myofibers. 

PMID- 25862247
TI  - Actin-dependent mitochondrial internalization in cardiomyocytes: evidence for
      rescue of mitochondrial function.
AB  - Previously, we have demonstrated that the transplantation of viable, structurally
      intact, respiration competent mitochondria into the ischemic myocardium during
      early reperfusion significantly enhanced cardioprotection by decreasing
      myocellular damage and enhancing functional recovery. Our in vitro and in vivo
      studies established that autologous mitochondria are internalized into
      cardiomyocytes following transplantation; however, the mechanism(s) modulating
      internalization of these organelles were unknown. Here, we show that
      internalization of mitochondria occurs through actin-dependent endocytosis and
      rescues cell function by increasing ATP content and oxygen consumption rates. We
      also show that internalized mitochondria replace depleted mitochondrial (mt)DNA.
      These results describe the mechanism for internalization of mitochondria within
      host cells and provide a basis for novel therapeutic interventions allowing for
      the rescue and replacement of damaged or impaired mitochondria. 

PMID- 25862248
TI  - Electrocardiographic criteria to differentiate acute anterior ST-elevation
      myocardial infarction from left ventricular aneurysm.
AB  - BACKGROUND: ST elevation (STE) on the electrocardiogram (ECG) may be due to acute
      myocardial infarction (AMI) or other nonischemic pathologies such as left
      ventricular aneurysm (LVA). The objective of this study was to validate 2
      previously derived ECG rules to distinguish AMI from LVA. The first rule states
      that if the sum of T-wave amplitudes in leads V1 to V4 divided by the sum of QRS
      amplitudes in leads V1 to V4 is greater than 0.22, then acute ST-segment
      elevation MI is predicted. The second rule states that if any 1 lead (V1-V4) has
      a T-wave amplitude to QRS amplitude ratio greater than or equal to 0.36, then
      acute ST-segment elevation MI is predicted. METHODS: This was a retrospective
      analysis of patients with AMI (n = 59) and LVA (n = 16) who presented with
      ischemic symptoms and STE on the ECG. For each ECG, the T-wave amplitude and QRS
      amplitude in leads V1 to V4 were measured. These measurements were applied to the
      2 ECG rules; and sensitivity, specificity, and accuracy in predicting AMI vs LVA
      were calculated. RESULTS: For rule 1 (sum of ratios in V1-V4), sensitivity was
      91.5%, specificity was 68.8%, and accuracy was 86.7% in predicting AMI. For rule
      2 (maximum ratio in V1-V4), sensitivity was 91.5%, specificity was 81.3%, and
      accuracy was 89.3% in predicting AMI. CONCLUSIONS: When patients present to the
      emergency department with ischemic symptoms and the differential diagnosis for
      STE on the ECG is AMI vs LVA, these 2 ECG rules may be helpful in differentiating
      these 2 pathologies. Both rules are highly sensitive and accurate in predicting
      AMI vs LVA.

PMID- 25862249
TI  - Shenfu, traditional Chinese medicine in sepsis: are we ready for it?

PMID- 25862250
TI  - Taking America's blood pressure: a public health response to pandemic
      hypertension.

PMID- 25862251
TI  - Politics, policies and public health.

PMID- 25862252
TI  - How robust is the calculation of health inequality trends by educational
      attainment in England and Wales using the Longitudinal Study?
AB  - BACKGROUND AND OBJECTIVES: Inequalities in mortality by educational attainment
      are wider in Eastern Europe than in West and Central Europe, but have thus far
      been largely limited to cross-sectional analyses. This study explored the
      potential to use the Longitudinal Study to describe trends in mortality
      inequality by educational attainment in England and Wales from 1971 to 2009 and
      the limitations in the available data. STUDY DESIGN: Comparison of cohort
      studies. METHODS: Data from the Office for National Statistics Longitudinal Study
      were used which takes a sample of respondees from each Census (1971-2001) and
      links them to death certification. Age-standardized mortality was calculated by
      educational attainment for those aged 25-69 years as was the Relative Index of
      Inequality and Slope Index of Inequality for men and women for each time period.
      RESULTS: Overall mortality declined in all categories of educational attainment
      for men and women from 1971. Limited data were collected on educational
      attainment in the Censuses prior to 2001, combined with the high proportion of
      respondents with missing data or reporting 'no education', meant that estimates
      of inequalities for the period 1971 to 2000 were very imprecise and likely to be
      misleading. For 2001-2009, the slope index of inequality was 268 (95% CI 57-478)
      and relative index of inequality was 0.61 (95% CI 0.13-1.10) for the total
      population; 354 (95% CI 72-636) and 0.67 (95% CI 0.14-1.21) respectively for men;
      and 231 (95% CI 72-389) and 0.66 (95% CI 0.21-1.11) respectively for women.
      CONCLUSIONS: Limited educational data in the Censuses prior to 2001 makes
      calculation of mortality inequalities by educational attainment in England and
      Wales imprecise and potentially misleading. International comparisons and time
      trend analyses using these data prior to 2001 should be done with great caution.

PMID- 25862253
TI  - Prognosis and Predictors of Rebleeding After Bronchial Artery Embolization in
      Patients with Active or Inactive Pulmonary Tuberculosis.
AB  - INTRODUCTION: The aim of this study was to characterize the prognosis and
      identify factors that contribute to rebleeding after bronchial artery
      embolization (BAE) in patients with active or inactive pulmonary tuberculosis
      (PTB). METHODS: Following a retrospective review, 190 patients had hemoptysis
      requiring BAE due to PTB in one hospital between 2006 and 2013. RESULTS: The
      median age at the time of diagnosis of PTB was 37 years and 54 years at the time
      of first episode of hemoptysis. Among 47 patients (24.7 %) who experienced
      rebleeding after BAE during the median follow-up period of 13.9 months
      [interquartile range (IQR) 2.3-36.0 months], bleeding recurred in 12 patients
      (6.3 %) within 1 month and in 15 patients (7.9 %) after 1 year. The median non
      recurrence time was 8.6 months (IQR 1.2-27.6 months). Independent predictors of
      rebleeding after BAE were tuberculous-destroyed lung [hazard ratio (HR) 3.0; 95 %
      confidence interval (CI) 1.5-6.2; p = 0.003], the use of anticoagulant agents
      and/or antiplatelet agents (HR 2.6; 95 % CI 1.1-5.8; p = 0.022), underlying
      chronic liver disease (HR 2.7; 95 % CI 1.1-4-6.9; p = 0.033), elevated pre-BAE C
      reactive protein (CRP) (mg/dL) (HR 2.4; 95 % CI 1.0-5.5; p = 0.048), and the
      existence of fungal ball (HR 2.1; 95 % CI 1.0-4.3; p = 0.050). CONCLUSIONS: The
      risk of rebleeding after BAE in active or inactive PTB was high, particularly in
      patients with tuberculous-destroyed lung, chronic liver disease, the use of
      anticoagulant agents and/or antiplatelet agents, elevated pre-BAE CRP, and the
      existence of fungal ball.

PMID- 25862254
TI  - Impact of spatial neglect on stroke rehabilitation: evidence from the setting of
      an inpatient rehabilitation facility.
AB  - OBJECTIVE: To examine the impact of spatial neglect on rehabilitation outcome,
      risk of falls, and discharge disposition in stroke survivors. DESIGN: Inception
      cohort. SETTING: Inpatient rehabilitation facility (IRF). PARTICIPANTS:
      Individuals with unilateral brain damage after their first stroke (N=108) were
      assessed at IRF admission and discharge. At admission, 74 of them (68.5%)
      demonstrated symptoms of spatial neglect as measured using the Kessler Foundation
      Neglect Assessment Process (KF-NAP). INTERVENTIONS: Usual and standard IRF care.
      MAIN OUTCOME MEASURES: The FIM, Conley Scale, number of falls, length of stay
      (LOS), and discharge disposition. RESULTS: The greater the severity of spatial
      neglect (higher KF-NAP scores) at IRF admission and the lower the FIM scores at
      admission as well as at discharge. Higher KF-NAP scores also correlated with
      greater LOS and lower FIM improvement rate. The presence of spatial neglect (KF
      NAP score>0), but not Conley Scale scores, predicted falls such that participants
      with spatial neglect fell 6.5 times more often than those without symptoms. More
      severe neglect, indicated by KF-NAP scores at IRF admission, reduced the
      likelihood of returning home at discharge. A model that took spatial neglect and
      other demographic, socioeconomic, and clinical factors into account predicted
      home discharge. Rapid FIM improvement during IRF stay and lower annual income
      level were significant predictors of home discharge. CONCLUSIONS: Spatial neglect
      after a stroke is a prevalent problem and may negatively affect rehabilitation
      outcome, risk of falls, and LOS.

PMID- 25862256
TI  - Subradiological cam deformity of the head-neck junction: an occult cause of hip
      pain and chondrolabral damage.
AB  - PURPOSE: The goal of this study was to determine how frequently the
      conventionally defined "idiopathic" chondrolabral hip injuries are associated
      with subradiological cam deformities of the head-neck junction and whether a
      protective femoral osteochondroplasty may improve the outcome of their
      arthroscopic treatment. METHODS: All the non-arthritic or pre-arthritic painful
      hips diagnosed as having a primary chondrolabral injury were retrospectively
      evaluated. Coxometric data, clinical history and physical findings were reviewed
      to rule out any possible secondary lesion. The medical records of the selected
      cases were analyzed as for imaging features, surgical findings and post
      arthroscopy outcome. RESULTS: Three cases out of 79 chondrolabral injuries were
      identified as "primary" on the basis of the preoperative assessment. All the
      three patients were female in their fourth decade and showed a joint damage
      consistent with undetected cam FAI (cartilage delamination in the anterolateral
      acetabular quadrant, minor pathology of the adjacent labrum with or without
      chondrolabral separation, abrasion signs and herniation pits along the
      anterolateral head-neck junction). The first patient received a simple
      chondrolabral treatment whose benefits deteriorated few months after surgery; the
      second patient underwent chondrolabral repair and femoral osteochondroplasty and
      is still pain-free; and the third patient had a beneficial revision arthroscopy
      for femoral osteochondroplasty after prior unsuccessful chondrolabral surgery.
      CONCLUSIONS: If a chondrolabral injury of the hip is associated with MR
      arthrographic and arthroscopic indirect signs of cam FAI, a subradiological head
      neck deformity should be considered despite normal alpha angles. In such cases, a
      protective femoral osteochondroplasty may increase the success rate of the
      chondrolabral repair. LEVEL OF EVIDENCE: IV.

PMID- 25862255
TI  - Mobility Is a Key Predictor of Change in Well-Being Among Older Adults Who
      Experience Falls: Evidence From the Vancouver Falls Prevention Clinic Cohort.
AB  - OBJECTIVE: To determine the factors that predict change in well-being over time
      in older men and women presenting to the falls prevention clinic. DESIGN:
      Prospective cohort study. SETTING: Falls prevention clinic. PARTICIPANTS:
      Community-dwelling older adults who were referred to the clinic after sustaining
      a fall (between N=244 and N=255, depending on the analysis). INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: The ICEpop CAPability measure for Older
      people, a measure of well-being or quality of life, was administered at baseline,
      6 months, and 12 months. We constructed linear mixed models to determine whether
      baseline predictor variables were related to baseline well-being and/or changes
      in well-being over time. In addition, we included interactions with sex to
      investigate the difference between men and women. Baseline predictors included 2
      measures of mobility--Short Performance Physical Battery and timed Up and Go test
      -and a measure of global cognitive function--Montreal Cognitive Assessment.
      RESULTS: All 3 predictors were associated with well-being at baseline (P<.05).
      Furthermore, both the Short Performance Physical Battery and the timed Up and Go
      test interacted with sex (P<.05) to predict changes in well-being over time.
      Follow-up analyses suggested that better mobility was protective against decline
      in well-being in men but was generally unrelated to changes in well-being in
      women. CONCLUSIONS: We found that 2 valid and reliable measures of mobility
      interacted with sex to predict changes in well-being over time. This is a
      critical research area to develop in order to appropriately tailor future
      intervention strategies targeting well-being in older fallers, a population at
      high risk of functional decline.

PMID- 25862257
TI  - Multiple system atrophy: the case for an international collaborative effort.

PMID- 25862258
TI  - In Vitro Neuroprotective Effect of Shikimic Acid Against Hydrogen Peroxide
      Induced Oxidative Stress.
AB  - Shikimic acid (SA), originally extracted from Illicium verum Hook. fil., is an
      indispensable starting material for the synthesis of the antiviral drug
      Oseltamivir (Tamiflu((r))) with very limited number of studies regarding its
      biological effects in vitro. Therefore, we here evaluated the thermoanalytical
      profile, redox properties, and in vitro effects of SA on human neuronal-like
      cells (SH-SY5Y). The thermoanalytical profile of SA was studied by using
      differential scanning calorimetry (DSC) and thermogravimetry/derivative
      thermogravimetry (TG/DTG) characterization. Both antioxidant potential and in
      vitro lipoperoxidation levels were analyzed. Cell viability and intracellular
      reactive species (RS) production was determined by DCF and SRB assays,
      respectively. Our results show in vitro antioxidant activity of SA without
      exerting cytotoxic effects on SH-SY5Y cells at tested concentrations of 10 nM, 10
      MUM, and 10 mM. In addition, SA protected the cells against H2O2-induced
      toxicity; effect that could be related, at least in part, with decreased
      intracellular RS production and its antioxidant potential. The present study
      shows evidence for neuroprotective actions of SA against oxidative stress-induced
      toxicity on SH-SY5Y cells, inviting for further investigation about its potential
      use in the context of oxidative stress-associated neurodegenerative diseases. 

PMID- 25862259
TI  - A symmetric multivariate leakage correction for MEG connectomes.
AB  - Ambiguities in the source reconstruction of magnetoencephalographic (MEG)
      measurements can cause spurious correlations between estimated source time
      courses. In this paper, we propose a symmetric orthogonalisation method to
      correct for these artificial correlations between a set of multiple regions of
      interest (ROIs). This process enables the straightforward application of network
      modelling methods, including partial correlation or multivariate autoregressive
      modelling, to infer connectomes, or functional networks, from the corrected ROIs.
      Here, we apply the correction to simulated MEG recordings of simple networks and
      to a resting-state dataset collected from eight subjects, before computing the
      partial correlations between power envelopes of the corrected ROItime-courses. We
      show accurate reconstruction of our simulated networks, and in the analysis of
      real MEGresting-state connectivity, we find dense bilateral connections within
      the motor and visual networks, together with longer-range direct fronto-parietal
      connections. 

PMID- 25862260
TI  - Validated automatic brain extraction of head CT images.
AB  - BACKGROUND: X-ray computed tomography (CT) imaging of the brain is commonly used
      in diagnostic settings. Although CT scans are primarily used in clinical
      practice, they are increasingly used in research. A fundamental processing step
      in brain imaging research is brain extraction - the process of separating the
      brain tissue from all other tissues. Methods for brain extraction have either
      been 1) validated but not fully automated, or 2) fully automated and informally
      proposed, but never formally validated. AIM: To systematically analyze and
      validate the performance of FSL's brain extraction tool (BET) on head CT images
      of patients with intracranial hemorrhage. This was done by comparing the manual
      gold standard with the results of several versions of automatic brain extraction
      and by estimating the reliability of automated segmentation of longitudinal
      scans. The effects of the choice of BET parameters and data smoothing is studied
      and reported. METHODS: All images were thresholded using a 0-100 Hounsfield unit
      (HU) range. In one variant of the pipeline, data were smoothed using a 3
      dimensional Gaussian kernel (sigma=1mm(3)) and re-thresholded to 0-100HU; in the
      other, data were not smoothed. BET was applied using 1 of 3 fractional intensity
      (FI) thresholds: 0.01, 0.1, or 0.35 and any holes in the brain mask were filled.
      For validation against a manual segmentation, 36 images from patients with
      intracranial hemorrhage were selected from 19 different centers from the MISTIE
      (Minimally Invasive Surgery plus recombinant-tissue plasminogen activator for
      Intracerebral Evacuation) stroke trial. Intracranial masks of the brain were
      manually created by one expert CT reader. The resulting brain tissue masks were
      quantitatively compared to the manual segmentations using sensitivity,
      specificity, accuracy, and the Dice Similarity Index (DSI). Brain extraction
      performance across smoothing and FI thresholds was compared using the Wilcoxon
      signed-rank test. The intracranial volume (ICV) of each scan was estimated by
      multiplying the number of voxels in the brain mask by the dimensions of each
      voxel for that scan. From this, we calculated the ICV ratio comparing manual and
      automated segmentation: ICVautomated/ICVmanual. To estimate the performance in a
      large number of scans, brain masks were generated from the 6 BET pipelines for
      1095 longitudinal scans from 129 patients. Failure rates were estimated from
      visual inspection. ICV of each scan was estimated and an intraclass correlation
      (ICC) was estimated using a one-way ANOVA. RESULTS: Smoothing images improves
      brain extraction results using BET for all measures except specificity (all
      p<0.01, uncorrected), irrespective of the FI threshold. Using an FI of 0.01 or
      0.1 performed better than 0.35. Thus, all reported results refer only to smoothed
      data using an FI of 0.01 or 0.1. Using an FI of 0.01 had a higher median
      sensitivity (0.9901) than an FI of 0.1 (0.9884, median difference: 0.0014,
      p<0.001), accuracy (0.9971 vs. 0.9971; median difference: 0.0001, p<0.001), and
      DSI (0.9895 vs. 0.9894; median difference: 0.0004, p<0.001) and lower specificity
      (0.9981 vs. 0.9982; median difference: -0.0001, p<0.001). These measures are all
      very high indicating that a range of FI values may produce visually
      indistinguishable brain extractions. Using smoothed data and an FI of 0.01, the
      mean (SD) ICV ratio was 1.002 (0.008); the mean being close to 1 indicates the
      ICV estimates are similar for automated and manual segmentation. In the 1095
      longitudinal scans, this pipeline had a low failure rate (5.2%) and the ICC
      estimate was high (0.929, 95% CI: 0.91, 0.945) for successfully extracted brains.
      CONCLUSION: BET performs well at brain extraction on thresholded, 1mm(3) smoothed
      CT images with an FI of 0.01 or 0.1. Smoothing before applying BET is an
      important step not previously discussed in the literature. Analysis code is
      provided.

PMID- 25862261
TI  - Orientation dependence of magnetization transfer parameters in human white
      matter.
AB  - Quantification of magnetization-transfer (MT) experiments is typically based on a
      model comprising a liquid pool "a" of free water and a semisolid pool "b" of
      motionally restricted macromolecules or membrane compounds. By a comprehensive
      fitting approach, high quality MT parameter maps of the human brain are obtained.
      In particular, a distinct correlation between the diffusion-tensor orientation
      with respect to the B0-magnetic field and the apparent transverse relaxation
      time, T2(b), of the semisolid pool (i.e., the width of its absorption line) is
      observed. This orientation dependence is quantitatively explained by a refined
      dipolar lineshape for pool b that explicitly considers the specific geometrical
      arrangement of lipid bilayers wrapped around a cylindrical axon. The model
      inherently reduces the myelin membrane to its lipid constituents, which is
      motivated by previous studies on efficient interaction sites (e.g., cholesterol
      or galactocerebrosides) in the myelin membrane and on the origin of ultrashort T2
      signals in cerebral white matter. The agreement between MT orientation effects
      and corresponding forward simulations using empirical diffusion imaging results
      as input as well as results from fits employing the novel lineshape support
      previous suggestions that the fiber orientation distribution in a voxel can be
      modeled as a scaled Bingham distribution. 

PMID- 25862262
TI  - Improving the reliability of single-subject fMRI by weighting intra-run
      variability.
AB  - At present, functional magnetic resonance imaging (fMRI) is one of the most
      useful methods of studying cognitive processes in the human brain in vivo, both
      for basic science and clinical goals. Although neuroscience studies often rely on
      group analysis, clinical applications must investigate single subjects (patients)
      only. Particularly for the latter, issues regarding the reliability of fMRI
      readings remain to be resolved. To determine the ability of intra-run variability
      (IRV) weighting to consistently detect active voxels, we first acquired fMRI data
      from a sample of healthy subjects, each of whom performed 4 runs (4 blocks each)
      of self-paced finger-tapping. Each subject's data was analyzed using single-run
      general linear model (GLM), and each block was then analyzed separately to
      calculate the IRV weighting. Results show that integrating IRV information into
      standard single-subject GLM activation maps significantly improved the
      reliability (p=0.007) of the single-subject fMRI data. This suggests that taking
      IRV into account can help identify the most constant and relevant neuronal
      activity at the single-subject level. 

PMID- 25862263
TI  - Dorsal striatum mediates cognitive control, not cognitive effort per se, in
      decision-making: An event-related fMRI study.
AB  - OBJECTIVE: Whether the dorsal striatum (DS) mediates cognitive control or
      cognitive effort per se in decision-making is unclear given that these effects
      are highly correlated. As the cognitive control requirements of a
      neuropsychological task intensify, cognitive effort increases proportionately. We
      implemented a task that disentangled cognitive control and cognitive effort to
      specify the particular function DS mediates in decision-making. METHODS: Sixteen
      healthy young adults completed a number Stroop task with simultaneous blood
      oxygenation-level-dependent response (BOLD) measurement using functional magnetic
      resonance imaging. Participants selected the physically larger number of a pair
      of single-digit integers. Discriminating smaller versus larger physical size
      differences between a number pair requires greater cognitive effort, but does not
      require greater cognitive control. We also investigated the effect of conflict
      between the physical and numerical dimensions of targets (e.g., 2 6). Selections
      in this incongruent case are more cognitively effortful and require greater
      cognitive control to suppress responding to the irrelevant dimension. Enhancing
      cognitive effort or cognitive control demands increases errors and response
      times. Despite similar behavioural profiles, our aim was to determine whether DS
      mediates cognitive control or simply indexes cognitive effort, using the same
      data set. RESULTS: As expected, behavioural interference effects occurred for
      both enhanced cognitive control and/or cognitive effort conditions. Despite
      similar degrees of behavioural interference, DS BOLD signal only correlated with
      interference arising due to increased cognitive control demands in the
      incongruent case. DS was not preferentially activated for discriminations of
      smaller relative to larger physical size differences between number pairs, even
      when using liberal statistical criteria. However, our incongruent and physical
      size effects conjointly activated regions related to effortful processing (e.g.,
      anterior cingulate cortex). INTERPRETATION: We interpret these findings as
      support for the increasingly accepted notion that DS mediates cognitive control
      specifically and does not simply index cognitive effort per se.

PMID- 25862264
TI  - Is fMRI "noise" really noise? Resting state nuisance regressors remove variance
      with network structure.
AB  - Noise correction is a critical step towards accurate mapping of resting state
      BOLD fMRI connectivity. Noise sources related to head motion or physiology are
      typically modelled by nuisance regressors, and a generalised linear model is
      applied to regress out the associated signal variance. In this study, we use
      independent component analysis (ICA) to characterise the data variance typically
      discarded in this pre-processing stage in a cohort of 12 healthy volunteers. The
      signal variance removed by 24, 12, 6, or only 3 head motion parameters
      demonstrated network structure typically associated with functional connectivity,
      and certain networks were discernable in the variance extracted by as few as 2
      physiologic regressors. Simulated nuisance regressors, unrelated to the true data
      noise, also removed variance with network structure, indicating that any group of
      regressors that randomly sample variance may remove highly structured "signal" as
      well as "noise." Furthermore, to support this we demonstrate that random sampling
      of the original data variance continues to exhibit robust network structure, even
      when as few as 10% of the original volumes are considered. Finally, we examine
      the diminishing returns of increasing the number of nuisance regressors used in
      pre-processing, showing that excessive use of motion regressors may do little
      better than chance in removing variance within a functional network. It remains
      an open challenge to understand the balance between the benefits and confounds of
      noise correction using nuisance regressors. 

PMID- 25862265
TI  - Mean-field thalamocortical modeling of longitudinal EEG acquired during intensive
      meditation training.
AB  - Meditation training has been shown to enhance attention and improve emotion
      regulation. However, the brain processes associated with such training are poorly
      understood and a computational modeling framework is lacking. Modeling approaches
      that can realistically simulate neurophysiological data while conforming to basic
      anatomical and physiological constraints can provide a unique opportunity to
      generate concrete and testable hypotheses about the mechanisms supporting complex
      cognitive tasks such as meditation. Here we applied the mean-field computational
      modeling approach using the scalp-recorded electroencephalogram (EEG) collected
      at three assessment points from meditating participants during two separate 3
      month-long shamatha meditation retreats. We modeled cortical, corticothalamic,
      and intrathalamic interactions to generate a simulation of EEG signals recorded
      across the scalp. We also present two novel extensions to the mean-field approach
      that allow for: (a) non-parametric analysis of changes in model parameter values
      across all channels and assessments; and (b) examination of variation in modeled
      thalamic reticular nucleus (TRN) connectivity over the retreat period. After
      successfully fitting whole-brain EEG data across three assessment points within
      each retreat, two model parameters were found to replicably change across both
      meditation retreats. First, after training, we observed an increased temporal
      delay between modeled cortical and thalamic cells. This increase provides a
      putative neural mechanism for a previously observed reduction in individual alpha
      frequency in these same participants. Second, we found decreased inhibitory
      connection strength between the TRN and secondary relay nuclei (SRN) of the
      modeled thalamus after training. This reduction in inhibitory strength was found
      to be associated with increased dynamical stability of the model. Altogether,
      this paper presents the first computational approach, taking core aspects of
      physiology and anatomy into account, to formally model brain processes associated
      with intensive meditation training. The observed changes in model parameters
      inform theoretical accounts of attention training through meditation, and may
      motivate future study on the use of meditation in a variety of clinical
      populations. 

PMID- 25862266
TI  - Decreases in theta and increases in high frequency activity underlie associative
      memory encoding.
AB  - Episodic memory encoding refers to the cognitive process by which items and their
      associated contexts are stored in memory. To investigate changes directly
      attributed to the formation of explicit associations, we examined oscillatory
      power captured through intracranial electroencephalography (iEEG) as 27
      neurosurgical patients receiving subdural and depth electrodes for seizure
      monitoring participated in a paired associates memory task. We examined low (3
      8Hz) and high (45-95Hz) frequency activity, and found that the successful
      formation of new associations was accompanied by broad decreases in low frequency
      activity and a posterior to anterior progression of increases in high frequency
      activity in the left hemisphere. These data suggest that the observed patterns of
      activity may reflect the neural mechanisms underlying the formation of novel item
      item associations. 

PMID- 25862268
TI  - Reliable activation to novel stimuli predicts higher fluid intelligence.
AB  - The ability to reliably respond to stimuli could be an important biological
      determinant of differences in fluid intelligence (Gf). However, most
      electrophysiological studies of Gf employ event-related potential (ERP) measures
      that average brain activity over trials, and hence have limited power to quantify
      neural variability. Time-frequency analyses can capture cross-trial variation in
      the phase of neural activity, and thus can help address the importance of neural
      reliability to differences in Gf. This study recruited a community sample of
      healthy adults and measured inter-trial phase clustering (ITPC), total spectral
      power, and ERP amplitudes elicited by Repeated and Novel non-target stimuli
      during two visual oddball tasks. Condition effects, relations among the EEG
      measures, and relations with Gf were assessed. Early visual responses to Repeated
      stimuli elicited higher ITPC, yet only ITPC elicited by Novel stimuli was
      associated with Gf. Analyses of spectral power further highlighted the
      contribution of phase consistency to the findings. The link between Gf and
      reliable responding to changing inputs suggests an important role for flexible
      resource allocation in fluid intellectual skills. 

PMID- 25862267
TI  - Understanding the dynamic relationship between cerebral blood flow and the BOLD
      signal: Implications for quantitative functional MRI.
AB  - Calibrated BOLD imaging, in which traditional measurements of the BOLD signal are
      combined with measurements of cerebral blood flow (CBF) within a BOLD biophysical
      model to estimate changes in oxygen metabolism (CMRO2), has been a valuable tool
      for untangling the physiological processes associated with neural stimulus
      induced BOLD activation. However, to date this technique has largely been applied
      to the study of essentially steady-state physiological changes (baseline to
      activation) associated with block-design stimuli, and it is unclear whether this
      approach may be directly extended to the study of more dynamic, naturalistic
      experimental designs. In this study we tested an assumption underlying this
      technique whose validity is critical to the application of calibrated BOLD to the
      study of more dynamic stimuli, that information about fluctuations in venous
      cerebral blood volume (CBVv) can be captured indirectly by measuring fluctuations
      in CBF, making the independent measurement of CBVv unnecessary. To accomplish
      this, simultaneous arterial spin labeling and BOLD imaging were used to measure
      the CBF and BOLD responses to flickering checkerboards with contrasts that
      oscillated continuously with frequencies of ~0.02-0.16Hz. The measurements were
      then fit to a dynamic physiological model of the BOLD response in order to
      explore the range of consistent CMRO2 and CBVv responses. We found that the BOLD
      and CBF responses were most consistent with relatively tight dynamic coupling
      between CBF and CMRO2 and a CBVv response that was an order of magnitude slower
      than either CBF or CMRO2. This finding suggests that the assumption of tight flow
      volume coupling may not be strictly valid, complicating the extension of
      calibrated BOLD to more naturalistic experimental designs. 

PMID- 25862269
TI  - Work flow for the prosthetic rehabilitation of atrophic patients with a minimal
      intervention CAD/CAM approach.
AB  - The implant-supported fixed rehabilitation of patients with an atrophic
      edentulous crest remains a challenge if bone augmentation is not planned. A
      minimal intervention approach for bone regeneration is necessary to minimize the
      flap overextension needed to close the defect over the augmented bone.
      Prosthetically guided bone regeneration can determine the amount of bone
      augmentation necessary for definitive prosthetic fixed rehabilitation. The
      positions of the implants and prosthetic restoration were planned; a 0.3 mm thick
      titanium mesh was customized for bone augmentation by using computer-aided design
      and computer-aided manufacturing and rapid prototyped by laser sintering, and the
      definitive prosthetic rehabilitation was carried out according to the initial
      treatment plan. This resulted in minimal bone augmentation relative to the
      functional needs of the definitive prosthetic rehabilitation. 

PMID- 25862270
TI  - Use of intraoral digital scanning for a CAD/CAM-fabricated milled bar and
      superstructure framework for an implant-supported, removable complete dental
      prosthesis.
AB  - This report describes a clinical technique for fabricating a maxillary implant
      supported, removable complete dental prosthesis by using an intraoral digital
      scanner to register implant positions and soft tissue morphology. The presented
      technique uses computer-aided design/computer-aided manufacturing (CAD/CAM)
      technology with a subtractive manufacturing process to fabricate a milled bar
      (infrastructure framework) and an additive process to fabricate a friction fit,
      superstructure framework. This digital restorative pathway may decrease patient
      discomfort and reduce the labor associated with fabricating implant-supported,
      removable complete dental prostheses.

PMID- 25862271
TI  - Replacement of missing posterior tooth with off-center placed single implant:
      Long-term follow-up outcomes.
AB  - STATEMENT OF PROBLEM: The distal offset placement of a single implant to replace
      a single tooth would overcome the shortcomings of the placement of a single wide
      implant in the posterior region. However, long-term evaluation is still-lacking.
      PURPOSE: The purpose of this study was to evaluate the long-term outcomes of
      patients treated with a single tooth restoration supported by a distal-offset
      placed implant. MATERIAL AND METHODS: Thirty-one patients with a single
      restoration supported by an off-center placed implant were evaluated. The
      patients' demographic data were described. The known implant length was used as a
      reference to calibrate the linear measurements on digital periapical radiographs.
      Implant details, survival, and prosthetic complications were analyzed. The
      implant survival rate was analyzed with the Kaplan-Meier method. RESULTS: Thirty
      four implants were placed with a distal offset to support single-tooth
      restorations. Twenty patients were women, and patient age was 56 +/- 12 years.
      The implants had a follow-up time from loading up to 10 years (average: 4 +/- 3
      years). Most of the implants were inserted in type II bone, and 85% were placed
      in the molar region. The distal offset placement of the implant and the selection
      of a wide-diameter implant resulted in a mesial bone loss of 0.85 +/- 0.57 mm and
      distal bone loss of 0.83 +/- 0.68 mm. One implant failed after 4 months from
      insertion, resulting in a cumulative survival rate of 97.1%. No prosthetic
      complications were registered. CONCLUSIONS: The distal offset placement of an
      implant is an efficient option for restoring a single missing posterior tooth
      when mesiodistal space is limited.

PMID- 25862272
TI  - Survival of teeth treated with cast post and cores: A retrospective analysis over
      an observation period of up to 19.5 years.
AB  - STATEMENT OF PROBLEM: Scientific data about the long-term survival of teeth
      treated with cast post and cores are scarce. Retrospective studies often use
      different target events for their analyses. A comparison is therefore
      complicated. For associated tooth-, jaw-, and patient-related factors little
      evidence exists as to their effect on survival. PURPOSE: The purpose of this
      study was to extend the knowledge on the survival of teeth treated with cast post
      and cores for observation periods of more than 10 years. A decrease or increase
      in survival times according to the presence or absence of associated parameters
      needs to be evaluated. MATERIAL AND METHODS: A retrospective evaluation was
      conducted of all cast post and cores inserted in 1 university clinic between
      January 1992 and June 2011. A Kaplan-Meier survival analysis was carried out by
      using extraction as the target event. The survival curves for different tooth
      types, the presence or absence of adjacent teeth, and the prosthetic restoration
      of the respective jaws were compared by using the log-rank test (alpha=.05). A
      Cox regression model was calculated for multivariate analyses. RESULTS: A total
      of 717 cast post and cores for 343 patients were recorded. The mean survival time
      was 13.5 years. A statistically significant decrease in survival times was found
      for canines (11.9 years) and premolars (13.4 years) versus molars (14.1 years),
      no adjacent teeth (10.6 years) versus at least 1 adjacent tooth (13.8 years), and
      the restoration with removable dental prostheses (12.5 years) versus fixed dental
      prostheses and single crowns (13.9 years). The largest reduction in survival time
      was found for teeth being used as an abutment for a double crown-retained
      removable partial dental prosthesis (telescopic denture) (9.8 years). Tooth type
      and adjacent tooth status remained as significant variables within the
      multivariate Cox regression model. CONCLUSIONS: Cast post and cores have an
      acceptable long-term survival time. Because different factors may influence
      survival, considering these factors in treatment planning may increase the long
      term success of these restorations.

PMID- 25862273
TI  - Association between developmental defects of enamel and dental caries: A
      systematic review and meta-analysis.
AB  - BACKGROUND: Dental caries is the main problem oral health and it is not well
      established in the literature if the enamel defects are a risk factor for its
      development. OBJECTIVE: Studies have reported a potential association between
      developmental defects enamel (DDE) and dental caries occurrence. We investigated
      the association between DDE and caries in permanent dentition of children and
      teenagers. DATA SOURCES: A systematic review was carried out using four databases
      (Pubmed, Web of Science, Embase, and Science Direct), which were searched from
      their earliest records until December 31, 2014. STUDY SELECTION: Population-based
      studies assessing differences in dental caries experience according to the
      presence of enamel defects (and their types) were included. PRISMA guidelines for
      reporting systematic reviews were followed. Meta-analysis was performed to assess
      the pooled effect, and meta-regression was carried out to identify heterogeneity
      sources. From the 2558 initially identified papers, nine studies fulfilled all
      inclusion criteria after checking the titles, abstracts, references, and complete
      reading. Seven of them were included in the meta-analysis with random model.
      RESULTS: A positive association between enamel defects and dental caries was
      identified; meta-analysis showed that individuals with DDE had higher pooled odds
      of having dental caries experience [OR 2.21 (95% CI 1.3; 3.54)]. Meta-regression
      analysis demonstrated that adjustment for sociodemographic factors, countries'
      socioeconomic status, and bias (quality of studies) explained the high
      heterogeneity observed. CONCLUSION: A higher chance of dental caries should be
      expected among individuals with enamel defects.

PMID- 25862274
TI  - Evaluation of penetration effect of resin infiltrant using optical coherence
      tomography.
AB  - OBJECTIVE: The aims of this in vitro study were to investigate whether optical
      coherence tomography (OCT) could analyze infiltration of resin infiltrant (RI)
      into early dental caries (EC), and to confirm the correlation between the results
      of OCT and confocal laser scanning microscopy (CLSM) for evaluation of RI
      infiltration into EC. METHODS: Sound bovine permanent teeth were used to produce
      sixty specimens by making two windows on the teeth. Each 20 specimens were
      demineralized for 20, 30, and 40 days, and the RI was treated on one of the
      windows. As a result, the images of the fifty-two specimens were taken by OCT and
      CLSM. The demineralized lesion depth (LDOCT and LDCLSM) and the infiltrated depth
      of RI into lesion (IDOCT and IDCLSM) obtained from the OCT and the CLSM were
      analyzed. The correlations between the LDOCT and the LDCLSM, and between the
      IDOCT and the IDCLSM, were analyzed by Pearson correlation and intra-class
      correlation. Also, Bland-Altman plot was constructed to assess the agreement
      between the IDOCT and the IDCLSM, and the IDOCT divided by refractive index of RI
      and the IDCLSM. RESULTS: The Pearson correlation coefficient and intra-class
      correlation of 0.75 and 0.83 (95% CI: 0.71-0.91) respectively were confirmed
      between the LDOCT and the LDCLSM (p<0.001), and 0.59 and 0.71 (95% CI: 0.50-0.84)
      respectively were observed between the IDOCT and the IDCLSM (p<0.001). The lower
      bias was confirmed in Bland-Altman plot between adjusted IDOCT and the IDCLSM
      than between the IDOCT and the IDCLSM. CONCLUSION: The OCT was the promising
      quantitative evaluation method for RI penetrated into EC. CLINICAL SIGNIFICANCE:
      The OCT would be used as a nondestructive and real-time evaluation method for RI
      penetrated into EC on clinical procedure.

PMID- 25862276
TI  - Validation of the 'Quality of Life with Implant Prostheses (QoLIP-10)'
      questionnaire for wearers of cement-retained implant-supported restorations.
AB  - OBJECTIVES: To validate the 'Quality of Life with Implant-Prostheses (QoLIP-10)'
      questionnaire for assessing the impact of cemented implant prostheses on Oral
      Health-Related Quality of Life (OHRQoL). METHODS: 84 subjects wearing implant
      restorations were distributed as follows: Group 1 (SD-I; n=35): screwed FDPs
      (fixed dental prostheses) supported by 2 implants; Group 2 (SD-II; n=7): screwed
      FDPs supported by 3-5 implants; Group 3 (CD-I; n=36): cemented FDPs supported by
      2 implants; and Group 4 (CD-II; n=6): cemented FDPs supported by 3-5 implants.
      The QoLIP-10 and the Oral Health Impact Profile (OHIP-14sp) scales were used.
      Data related to global oral satisfaction, socio-demographics, health-behaviors,
      and prostheses, were gathered. Reliability and validity of the QoLIP-10 were
      investigated. Correlations between both indices were explored with the Spearman's
      rank test. Descriptive and non-parametric probes were run to evaluate the effect
      of the study variables on the OHRQoL (alpha=0.05). RESULTS: The QoLIP-10
      confirmed its psychometric capacity for cemented implant prosthesis wearers. Both
      tests were inversely correlated. The QoLIP-10 attributed the significantly worst
      QoL to long-span cemented prostheses. Groups were significantly discriminated by
      the QoLIP-10 performance dimension. The variable complaints about the mouth and
      the three global oral satisfaction measures significantly modulated the OHRQoL.
      CONCLUSIONS: Patient satisfaction depends upon the extension and the type of
      retention of implant FDPs. CLINICAL SIGNIFICANCE: The QoLIP-10 may help
      estimating the effect of cemented FDPs on patients' well-being. When compared to
      screwed FDPs, short cemented implant restorations lead to greater improvements in
      patients' self-perceived QoL.

PMID- 25862275
TI  - Assessment of remineralization via measurement of dehydration rates with thermal
      and near-IR reflectance imaging.
AB  - OBJECTIVES: Previous studies have demonstrated that the optical changes due to
      the loss of water from porous lesions can be exploited to assess lesion severity
      with QLF, thermal and near-IR imaging. Since arrested lesions are less permeable
      to water due to the highly mineralized surface layer, changes in the rate of
      water loss can be related to changes in lesion structure. The purpose of this
      study was to investigate whether the rate of water loss correlates with the
      degree of remineralization and whether that rate can be measured using thermal
      and near-IR reflectance imaging. METHODS: Artificial bovine enamel lesions (n=30)
      were prepared by immersion in a demineralization solution for either 8 and 24 h
      and they were subsequently placed in an acidic remineralization solution for
      different periods. The samples were dehydrated using an air spray for 30s and
      surfaces were imaged using a thermal camera and an InGaAs camera at 1300-1700 nm
      wavelengths. RESULTS: The area enclosed by the time-temperature curve, DeltaQ,
      from thermal imaging showed significant differences (P<0.05) between the lesion
      window and other windows. Near-IR reflectance intensity differences, DeltaI,
      before and after dehydration decreased with longer periods of remineralization.
      Only near-IR reflectance imaging was capable of detecting significant differences
      (P<0.05) between the different periods of remineralization. CONCLUSIONS: This
      study demonstrated that both thermal and near-IR reflectance imaging were
      suitable for the detection of remineralization in simulated caries lesions and
      near-IR wavelengths longer than 1400 nm are well suited for the assessment of
      remineralization.

PMID- 25862277
TI  - Setting characteristics of a resin infiltration system for incipient caries
      treatment.
AB  - OBJECTIVES: This study investigated the curing efficiency, the extent of
      atmospheric oxygen inhibition to the polymerization reaction and the mechanical
      properties of a new resin-infiltration system for caries treatment. METHODS: The
      curing efficiency was estimated by measuring the percentage degree of cure (%DC)
      of thin resin films (h: 150MUm, O: 5mm, n=3), 10min after 40s exposure to a
      quartz halogen bulb (750mW/cm2) light curing unit (Optilux 501, Demetron/Kerr,
      USA), in the absence of O2, by micro ATR-FTIR spectroscopy. The extent of O2
      inhibition on resin film setting (width in MUm) was assessed by transmission
      optical microscopy on thin films (h: 150MUm, O: ~7mm, n=5) placed between two
      transparent cover slips and exposed to air from lateral sites. For each sample
      the extent of inhibition was measured at 5 different locations. The mechanical
      properties were tested employing Instrumented Indentation Testing according to
      ISO 14577:2002. Resin specimens (h: 2mm, O: 10mm, n=5) were prepared employing
      cylindrical teflon moulds enclosed in transparent matrix strips and glass slides
      as before. The measurements were performed employing a Vickers indenter attached
      to a universal hardness testing machine (ZHU2.5/Z2.5 plus test Xpert software,
      Zwick/Roell, Ulm, Germany). The parameters tested were Martens Hardness (MH),
      Vickers Hardness (VHN), Indentation Elastic Modulus (EIT) and elastic to total
      ratio of indentation work (etaIT). For all these tests, specimens of a
      conventional light-curing bonding resin (HB-Heliobond, Ivoclar-Vivadent, FL)
      prepared as above were used as control. Student t-test was used to identify
      statistically significant differences between the two materials in the parameters
      tested (a: 0.05). RESULTS: The results of the materials tested were: (a) [% DC];
      IC: 57.4+/-1.5, HB: 59.8+/-2.4, (b) [Width of O2 inhibition/MUm]; IC: 33.1+/-6.5,
      HB: 23.6+/-4.4, (c) [MH/N/mm(2)] IC; 116+/-16, HB: 261+/-35, (d) [VHN]; IC;
      15.4+/-2.5, HB: 22.1+/-1.8, (e) [EIT/(GPa)]; IC; 2.3+/-0.4, HB: 7.5+/-0.5, and
      (g) [etaIT (%)] IC; 50.3+/-3.4, HB: 35.1+/-1.9. The IC presented no significant
      difference in terms of % DC, higher thickness of the inhibited layer, lower MH,
      VHN, EIT and greater etaIT values than HB. CONCLUSIONS AND CLINICAL SIGNIFICANT:
      The resin-infiltrating system for incipient caries treatment demonstrated the
      same curing efficiency with a conventional unfilled bonding resin, but exhibited
      higher extent of oxygen inhibition, lower hardness, lower elastic modulus and
      higher plastic to elastic indentation energy.

PMID- 25862278
TI  - Detection and treatment of proximal caries lesions: Milieu-specific cost
      effectiveness analysis.
AB  - OBJECTIVES: Dental caries lesions are highly prevalent, concentrated in high-risk
      groups, and often affect proximal tooth surfaces. Choosing a caries detection
      method determines the available treatment options: radiographically detected
      early lesion stages might receive non-, micro-, or invasive treatments, whilst
      visually tactile detected lesions are often advanced and mostly require invasive
      treatment. Thus, the choice of detection method impacts on patients via the
      applied treatment. We compared the cost-effectiveness of combinations of
      detections and treatments of proximal lesions in different populations which did
      or did not receive prevention during adolescence. These cost-effectiveness
      comparisons of different detection-treatment combinations should aid clinical
      decision making and improve resource allocation. METHODS: A Markov-model was
      constructed to follow a proximal posterior surface in a 12-year-old German over
      his lifetime. Prevalence, validity and transition probabilities were extracted
      from the literature. Microsimulations were performed to evaluate costs (Euro) per
      tooth-retention-time (years). RESULTS: For populations with low risk,
      radiographic detection plus non-invasive treatment without (270 Euro, 61.5 years)
      and with prevention (312 Euro, 63.0 years), as well as radiographic detection
      plus micro-invasive treatment and prevention (373 Euro, 64.0 years) were cost
      effective. For populations with high risk, radiographic detection plus micro
      invasive treatment without (427 Euro, 58.5 years) and with prevention (436 Euro,
      61.0 years) were cost-effective. Combinations involving invasive treatments had
      limited cost-effectiveness. CONCLUSIONS: Caries detection methods should be
      evaluated regarding the cost-effectiveness resulting from their use in different
      populations. CLINICAL SIGNIFICANCE: Caries detection methods are usually
      evaluated regarding their validity compared to a gold standard. We demonstrate
      that the cost-effectiveness stemming from using different detection methods
      additionally depends on the treatment options determined by different methods,
      and the examined population. Dentists' choice of a detection method should not
      only be guided by its validity, but also by its specific benefits in different
      populations.

PMID- 25862279
TI  - Epidemiology and molecular characterisation of duck hepatitis A virus from
      different duck breeds in Egypt.
AB  - Duck hepatitis virus (DHV) is an acute highly contagious disease of ducklings
      caused by three distinct serotypes of duck hepatitis A virus (DHAV), a member of
      the RNA family Picornaviridae, where serotype 1 is the most widespread serotype
      worldwide. To date, little if any is known about the prevalence and genetic
      characterisation of DHAV outside Asia. The current study describes surveillance
      on DHV in 46 commercial duck farms in Egypt with a history of high mortality in
      young ducklings from 3 to 15 day-old from 2012 to 2014. Clinical samples were
      examined by generic RT-PCR assays followed by partial sequence analysis of the
      5'UTR, VP1 and 3D genes of the vaccine strain and 15 field viruses. The overall
      positive rate was 37% (n=17/46). All duck breeds (Pekin, Muscovy, Mallard and
      Green Winged) were susceptible to the disease with mortality ranged from 15% to
      96.7%. Sequence and phylogenetic analyses indicated that the Egyptian strains
      cluster in the DHAV serotype 1 with Asian viruses and distinguishable from the
      vaccine strains. So far, this is the first report on the genetic characterisation
      of DHAV in Egypt. This study may be useful to better understand the epidemiology
      and evolution of DHAV. 

PMID- 25862280
TI  - Multilocus sequence typing of Australian Streptococcus suis type 2 by MALDI-TOF
      mass spectrometry analysis of PCR amplicons.
AB  - Streptococcus suis serotype 2 is a ubiquitous pathogen of swine and is known to
      cause severe disease in humans. Multilocus sequence typing (MLST) is ideal for
      characterising this organism because it permits isolates to be compared on a
      national and international scale. A novel approach to MLST using matrix-assisted
      laser desorption ionisation-time of flight mass spectrometry (MS-MLST) provides a
      more rapid alternative to dideoxy sequencing. This study used MS-MLST to define
      the multilocus sequence types (STs) present among a collection of Australian S.
      suis type 2, and thus, delivered a basis for comparison of Australian isolates
      with international strains already well characterised for virulence attributes. A
      collection of 45 isolates recovered from infected humans (n=3) and diseased pigs
      (n=42) was genotyped using MS-MLST and conventional MLST. Both methods were 100%
      concordant in their classification of sequence types (STs), although MS-MLST
      permitted much quicker analysis of sequence data. The collection contained ST25
      (n=31), ST1 (n=10), ST28 (n=3) and ST369 (n=1). These results are consistent with
      the population structure of S. suis type 2 observed in diseased pigs and humans
      in Canada and the United Kingdom. MS-MLST may have utility for studying the
      population structure and epidemiology of S. suis in countries where the diversity
      of S. suis is greater and human disease is more common. 

PMID- 25862281
TI  - Plasma and Plasma Protein Product Transfusion: A Canadian Blood Services Centre
      for Innovation Symposium.
AB  - Plasma obtained via whole blood donation processing or via apheresis technology
      can either be transfused directly to patients or pooled and fractionated into
      plasma protein products that are concentrates of 1 or more purified plasma
      protein. The evidence base supporting clinical efficacy in most of the
      indications for which plasma is transfused is weak, whereas high-quality evidence
      supports the efficacy of plasma protein products in at least some of the clinical
      settings in which they are used. Transfusable plasma utilization remains composed
      in part of applications that fall outside of clinical practice guidelines. Plasma
      contains all of the soluble coagulation factors and is frequently transfused in
      efforts to restore or reinforce patient hemostasis. The biochemical complexities
      of coagulation have in recent years been rationalized in newer cell-based models
      that supplement the cascade hypothesis. Efforts to normalize widely used clinical
      hemostasis screening test values by plasma transfusion are thought to be
      misplaced, but superior rapid tests have been slow to emerge. The advent of non
      vitamin K-dependent oral anticoagulants has brought new challenges to clinical
      laboratories in plasma testing and to clinicians needing to reverse non-vitamin K
      dependent oral anticoagulants urgently. Current plasma-related controversies
      include prophylactic plasma transfusion before invasive procedures, plasma vs
      prothrombin complex concentrates for urgent warfarin reversal, and the utility of
      increased ratios of plasma to red blood cell units transfused in massive
      transfusion protocols. The first recombinant plasma protein products to reach the
      clinic were recombinant hemophilia treatment products, and these donor-free
      equivalents to factors VIII and IX are now being supplemented with novel products
      whose circulatory half-lives have been increased by chemical modification or
      genetic fusion. Achieving optimal plasma utilization is an ongoing challenge in
      the interconnected worlds of transfusable plasma, plasma protein products, and
      recombinant and engineered replacements. 

PMID- 25862283
TI  - Bcl-xL stimulates Bax relocation to mitochondria and primes cells to ABT-737.
AB  - Bax cytosol-to-mitochondria translocation is a central event of the intrinsic
      pathway of apoptosis. Bcl-xL is an important regulator of this event and was
      recently shown to promote the retrotranslocation of mitochondrial Bax to the
      cytosol. The present study identifies a new aspect of the regulation of Bax
      localization by Bcl-xL: in addition to its role in Bax inhibition and
      retrotranslocation, we found that, like with Bcl-2, an increase of Bcl-xL
      expression levels led to an increase of Bax mitochondrial content. This finding
      was substantiated both in pro-lymphocytic FL5.12 cells and a yeast reporting
      system. Bcl-xL-dependent increase of mitochondrial Bax is counterbalanced by
      retrotranslocation, as we observed that Bcl-xLDeltaC, which is unable to promote
      Bax retrotranslocation, was more efficient than the full-length protein in
      stimulating Bax relocation to mitochondria. Interestingly, cells overexpressing
      Bcl-xL were more sensitive to apoptosis upon treatment with the BH3-mimetic ABT
      737, suggesting that despite its role in Bax inhibition, Bcl-xL also primes
      mitochondria to permeabilization and cytochrome c release. 

PMID- 25862284
TI  - Multi-institutional analysis of renal function outcomes following radical
      nephroureterectomy and partial ureterectomy for upper tract urothelial carcinoma.
AB  - PURPOSE: To compare renal function outcomes in patients undergoing radical
      nephroureterectomy (RNU) or partial (distal) ureterectomy (PU) for upper tract
      urothelial carcinoma (UTUC). METHODS: Clinicopathologic data of patients
      undergoing RNU or PU for UTUC from 1998 to 2012 were compiled. Glomerular
      filtration rate was calculated preoperatively and postoperatively using the
      Modification of Diet in Renal Disease equation. We defined "event" as new-onset
      stage III chronic kidney disease (CKD) or worsening of CKD stage with preexisting
      CKD. Event-free survival was assessed with Kaplan-Meier methods. Cox regression
      analyses were performed to identify predictors of events. RESULTS: In total, 193
      patients underwent RNU (n = 143) or PU (n = 50) over a median follow-up of 25.9
      months. Overall, 15% of patients died of UTUC. High tumor grade (85.9% vs. 66.0%,
      P = 0.003) and locally advanced stage (>pT2, 37.8% vs. 18.0%, P = 0.014) were
      significantly more frequent in the RNU cohort. Stage III or higher CKD was
      present in 61% of RNU patients vs. 48% of PU patients (P = 0.135) at baseline.
      Although total event rate was higher in the PU cohort (66% vs. 43.4%, P = 0.008),
      event rates within the first 3 months of surgery were similar between the groups
      (P = 0.572). Adjuvant chemotherapy was the only predictor of events on Cox
      regression. CONCLUSIONS: Rates of new-onset CKD or worsening of CKD stage were
      similar in patients treated with RNU and PU. Adjuvant chemotherapy may have a
      more significant effect on renal outcomes than surgical approach, warranting
      further investigation. Consideration should be given to preoperative
      chemotherapy, as adjuvant chemotherapy is limited by decreased renal function
      following surgery.

PMID- 25862285
TI  - Small renal mass management in the elderly and the calibration of risk.
AB  - Due to the increased utilization of cross-sectional imaging and prolonged life
      expectancy, the incidence of incidentally diagnosed renal tumors continues to
      rise. While partial nephrectomy is currently recommended as the gold standard
      treatment of cT1a small renal mass whenever technically feasible, the perceived
      benefits of partial nephrectomy may not be applicable to all patient groups.
      Selecting between treatment options in elderly and the infirm can present a
      significant challenge. Informed and thoughtful small renal mass management
      decisions require consideration and balance of patient, tumor, and procedural
      risks to maintain oncological efficacy while minimizing treatment associated
      morbidity. Herein we review the comparative effectiveness of partial versus
      radical nephrectomy in the elderly and the role of standardized tools to quantify
      risk. 

PMID- 25862282
TI  - The abundance of functional genes, cbbL, nifH, amoA and apsA, and bacterial
      community structure of intertidal soil from Arabian Sea.
AB  - The Gulf of Cambay is a trumpet-shaped inlet of the Arabian Sea, located along
      the west coast of India and confronts a high tidal range with strong water
      currents. The region belongs to a semi-arid zone and saline alkaline intertidal
      soils are considered biologically extreme. The selected four soil types (S1-S4)
      were affected by salinity, alkalinity and sodicity. Soil salinity ranged from 20
      to 126 dS/m, soil pH 8.6-10.0 with high sodium adsorption ratio (SAR) and
      exchangeable sodium percentage (ESP). Abundance of the key functional genes like
      cbbL, nifH, amoA and apsA involved in biogeochemical cycling were targeted using
      qPCR, which varied from (2.36 +/- 0.03) * 10(4) to (2.87 +/- 0.26) * 10(8), (1.18
      +/- 0.28) * 10(6) to (1.01 +/- 0.26) * 10(9), (1.41 +/- 0.21) * 10(6) to (1.29 +/
      0.05) * 10(8) and (8.47 +/- 0.23) * 10(4) to (1.73 +/- 0.01) * 10(6) per gram
      dry weight, respectively. The microbial community structure revealed that soils
      S1 and S3 were dominated by phylum Firmicutes whereas S4 and S2 showed an
      abundance of Proteobacterial clones. These soils also represented Bacteroidetes,
      Chloroflexi, Actinobacteria, Planctomycetes and Acidobacteria clones. Molecular
      phylogeny showed a significant variation in the bacterial community distribution
      among the intertidal soil types. A high number of novel taxonomic units were
      observed which makes the intertidal zone a unique reservoir of unidentified
      bacterial taxa that may be explored further.

PMID- 25862286
TI  - Studying tauopathies in Drosophila: A fruitful model.
AB  - Tauopathies are a group of neurodegenerative disorders that include hereditary
      frontotemporal dementias (FTDs) such as FTD with parkinsonism linked to
      chromosome 17 (FTDP-17), as well as sporadic variants of FTDs like progressive
      supranuclear palsy (PSP), corticobasal degeneration (CBD), and Pick's disease.
      These diverse diseases all have in common the presence of abnormally
      phosphorylated tau aggregates. In this review, we will summarize key features of
      transgenic Drosophila models of tauopathies and a number of insights into disease
      mechanisms as well as therapeutic implications gained from the fruit fly models. 

PMID- 25862288
TI  - Characterization and therapeutic evaluation of a Nestin+ CNP+ NG2+ cell
      population on mouse spinal cord injury.
AB  - The NG2 chondroitin sulfate proteoglycan-expressing neural cells (NG2 cells) have
      originally been considered as oligodendrocyte progenitor cells (OPCs). However,
      recent findings on their diverse functions and lineage heterogeneity demonstrated
      that the NG2 cells contain various sub-populations whose concrete features and
      therapeutic potential yet remained elucidated. In the present study, we
      characterized a Nestin(+) 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP)(+)
      NG2(+) subpopulation from embryonic rat cerebral cortex. The Nestin(+) CNP(+)
      NG2(+) cells exhibited remarkable progenitor characteristics. Having been
      immortalized by human telomerase reverse transcriptase (hTERT), the life span of
      Nestin(+) CNP(+) NG2(+) cells was extended to 230 population doublings (PDs).
      With immortalized NG2 cells, we demonstrated their differentiation capacities to
      oligodendrocytes, astrocytes and neurons. Furthermore, transplanted into injured
      spinal cord of a mouse model, they were able to promote remyelination and
      neuronal regeneration, thereby enhancing the functional recovery. Our findings
      suggest that the Nestin(+) CNP(+) NG2(+) progenitor cells could be a good
      alternative cell source of cell therapy for neurological disorders. 

PMID- 25862289
TI  - Chondroitin sulfate proteoglycans impede myelination by oligodendrocytes after
      perinatal white matter injury.
AB  - Hypomyelination is the major cause of neurodevelopmental deficits that are
      associated with perinatal white matter injury. Chondroitin sulfate proteoglycans
      (CSPGs) are known to exert inhibitory effects on the migration and
      differentiation of oligodendrocytes (OLs). However, few studies describe the
      roles of CSPGs in myelination by OLs and the cognitive dysfunction that follows
      perinatal white matter injury. Here, we examined the alterations in the
      expression of CSPGs and their functional impact on the maturation of OLs and
      myelination in a neonatal rat model of hypoxic-ischemic (HI) brain injury. Three
      day-old Sprague-Dawley rats underwent a right common carotid artery ligation and
      were exposed to hypoxia (6% oxygen for 2.5h). Rats were given chondroitinase ABC
      (cABC) via an intracerebroventricular injection to digest CSPGs. Animals were
      sacrificed at 7, 14, 28 and 56days after HI injury and the accompanying surgical
      procedure. We found that the expression of CSPGs was significantly up-regulated
      in the cortical regions surrounding the white matter after HI injury. cABC
      successfully degraded CSPGs in the rats that received cABC. Immunostaining showed
      decreased expression of the pre-oligodendrocyte marker O4 in the cingulum,
      external capsule and corpus callosum in HI+cABC rats compared to HI rats. However
      HI+cABC rats exhibited greater maturation of OLs than did HI rats, with increased
      expression of O1 and myelin basic protein in the white matter. Furthermore, using
      electron microscopy, we demonstrated that myelin formation was enhanced in
      HI+cABC rats, which had an increased number of myelinated axons and decreased G
      ratios of myelin compared to HI rats. Finally, HI+cABC rats performed better in
      the Morris water maze task than HI rats, which indicates an improvement in
      cognitive ability. Our results suggest that CSPGs inhibit both the maturation of
      OLs and the process of myelination after neonatal HI brain injury. The data also
      raise the possibility that modifying CSPGs may repair this type of lesion
      associated with demyelination. 

PMID- 25862290
TI  - Comparison of cyclic and impact-based reference point indentation measurements in
      human cadaveric tibia.
AB  - Although low bone mineral density (BMD) is strongly associated with increased
      fracture risk, up to 50% of those who suffer fractures are not detected as high
      risk patients by BMD testing. Thus, new approaches may improve identification of
      those at increased risk for fracture by in vivo assessment of altered bone tissue
      properties, which may contribute to skeletal fragility. Recently developed
      reference point indentation (RPI) allows for assessment of cortical bone
      indentation properties in vivo using devices that apply cyclic loading or impact
      loading, but there is little information available to assist with interpretation
      of RPI measurements. Our goals were to use human cadaveric tibia to determine: 1)
      the associations between RPI variables, cortical bone density, and morphology; 2)
      the association between variables obtained from RPI systems using cyclic, slow
      loading versus a single impact load; and 3) age-related differences in RPI
      variables. We obtained 20 human tibia and femur pairs from female donors (53
      97years), measured total hip BMD using dual-energy X-ray absorptiometry, assessed
      tibial cortical microarchitecture using high-resolution peripheral quantitative
      computed tomography (HR-pQCT), and assessed cortical bone indentation properties
      at the mid-tibial diaphysis using both the cyclic and impact-based RPI systems
      (Biodent and Osteoprobe, respectively, Active Life Scientific, Santa Barbara,
      CA). We found a few weak associations between RPI variables, BMD, and cortical
      geometry; a few weak associations between measurements obtained by the two RPI
      systems; and no age-related differences in RPI variables. Our findings indicate
      that in cadaveric tibia from older women RPI measurements are largely independent
      of age, femoral BMD, and cortical geometry. Furthermore, measurements from the
      cyclic and impact loading RPI devices are weakly related to each other,
      indicating that each device reflects different aspects of cortical bone
      indentation properties.

PMID- 25862287
TI  - Neurodevelopmental implications of the general anesthesia in neonate and infants.
AB  - Each year, about six million children, including 1.5 million infants, in the
      United States undergo surgery with general anesthesia, often requiring repeated
      exposures. However, a crucial question remains of whether neonatal anesthetics
      are safe for the developing central nervous system (CNS). General anesthesia
      encompasses the administration of agents that induce analgesic, sedative, and
      muscle relaxant effects. Although the mechanisms of action of general anesthetics
      are still not completely understood, recent data have suggested that anesthetics
      primarily modulate two major neurotransmitter receptor groups, either by
      inhibiting N-methyl-D-aspartate (NMDA) receptors, or conversely by activating
      gamma-aminobutyric acid (GABA) receptors. Both of these mechanisms result in the
      same effect of inhibiting excitatory activity of neurons. In developing brains,
      which are more sensitive to disruptions in activity-dependent plasticity, this
      transient inhibition may have longterm neurodevelopmental consequences.
      Accumulating reports from preclinical studies show that anesthetics in neonates
      cause cellular toxicity including apoptosis and neurodegeneration in the
      developing brain. Importantly, animal and clinical studies indicate that exposure
      to general anesthetics may affect CNS development, resulting in long-lasting
      cognitive and behavioral deficiencies, such as learning and memory deficits, as
      well as abnormalities in social memory and social activity. While the casual
      relationship between cellular toxicity and neurological impairments is still not
      clear, recent reports in animal experiments showed that anesthetics in neonates
      can affect neurogenesis, which could be a possible mechanism underlying the
      chronic effect of anesthetics. Understanding the cellular and molecular
      mechanisms of anesthetic effects will help to define the scope of the problem in
      humans and may lead to preventive and therapeutic strategies. Therefore, in this
      review, we summarize the current evidence on neonatal anesthetic effects in the
      developmental CNS and discuss how factors influencing these processes can be
      translated into new therapeutic strategies. 

PMID- 25862292
TI  - [Cardiology in the Morgagni's anatomo pathological work].
AB  - In the XVIII century, under the influence of the "systematic spirit",
      characteristic of the Enlightenment age, pathological anatomy was systematized in
      the Morgagni's fundamental treatise De sedibus et causis morborum per anatomen
      indagatis, published as letters in 1761. Certain biographical data of the author
      are reported here as well as some his more important contributions to cardiology
      such as the Morgagni's, Adams', Stokes' syndrome. His points of view on sudden
      death and his observations on post-infarct myocardial rupture, are related also.
      In his global evaluation of these facts, the speculative approach always
      predominates. Indeed, in these anatomist's works, we find a good example of the
      application of epistemologic principles to the medical field.

PMID- 25862291
TI  - The hepatitis B virus ribonuclease H as a drug target.
AB  - Chronic hepatitis B virus (HBV) infection is a leading cause of hepatitis, liver
      failure, and hepatocellular carcinoma. An outstanding vaccine is available;
      however, the number of infections remains high. Current anti-HBV treatments with
      interferon alpha and nucleos(t)ide analogs clear the infection in only a small
      minority of patients, and either induce serious side-effects or are of very long
      duration. HBV is a small, enveloped DNA virus that replicates by reverse
      transcription via an RNA intermediate. The HBV ribonuclease H (RNaseH) is
      essential for viral replication, but it has not been exploited as a drug target.
      Recent low-throughput screening of compound classes with anti-Human
      Immunodeficiency Virus RNaseH activity led to identification of HBV RNaseH
      inhibitors in three different chemical families that block HBV replication. These
      inhibitors are promising candidates for development into new anti-HBV drugs. The
      RNaseH inhibitors may help improve treatment efficacy enough to clear the virus
      from the liver when used in combination with existing anti-HBV drugs and/or with
      other novel inhibitors under development. This article forms part of a symposium
      in Antiviral Research on "An unfinished story: from the discovery of the
      Australia antigen to the development of new curative therapies for hepatitis B." 

PMID- 25862293
TI  - [From the medieval hospitals hospices to modern National public Health
      Institutes].
AB  - Since the most ancient times, hospital constructions and progresses in the
      clinical practice advanced pari passu. We can find exampless of this statement in
      Greek regions as well as in Greek citie overseas. Thus, during the renaissance,
      great figures ot that time converged in Italy: The genius Leonardo da Vinci (1452
      1519) and Leon Battista Alberti (1404-1472), a humanist and innovator of
      architecture. Michelangelo Buonarroti (1475-1564) and his contemporany artists
      performed anatomical dissection to perfect their art by studying the human body.
      Anatomical studies flourished at the University of Padua, driven by the Flemish
      Master. Based on the rigorous study of the anatomical substrate, the studies on
      the function of the already known organic structures excelled in the xvii
      century. That century started with the revelation of the major blood circulation
      by the British physician William Harvey, alumni of the University of Padua, and
      continued with the description of the minior or pulmonary circulation by ancient
      or contemporany authors and of the peripheral connections between the arterial
      and the venous system (Marcelo Malpighi, 1661). All these researchers, and
      others, were membres of the University of Padua, were the beneficial influence of
      the teachings of Galileo persisted. In the following centuries, together with the
      embryological and normal anatomy, the pathological anatomy, systematized by G.B.
      Morgani, became the cornerstone of the clinical practice. The model of the
      ancient hospitals evolved to ward the National Institutes of Health in Mexico
      fostered by Dr. Ignacio Chavez. 

PMID- 25862294
TI  - A population-based cohort study of stillbirth among twins in Lusaka, Zambia.
AB  - OBJECTIVE: To determine rates of stillbirth and the associated risk factors for
      stillbirth among twins delivered in Lusaka, Zambia. METHODS: A retrospective
      cohort analysis was conducted of singletons and twins delivered at 26 public
      sector facilities between February 1, 2006, and May 31, 2013. Data were obtained
      from the Zambian Electronic Perinatal Record System. Risk of stillbirth was
      estimated using logistic regression. RESULTS: Overall, 260 657 singletons and
      4021 twin pairs were included. There were 5105 stillbirths; 317 twins were
      stillborn. The crude stillbirth rate for twins was 39.4 per 1000 births (95%
      confidence interval [CI] 35.2-43.7) whereas the rate for singletons was 18.4 per
      1000 births (95% CI 17.9-18.9; P<0.001). Factors associated with stillbirth among
      twins were increased interval between delivery (>60 minutes), low birth weight
      (<2500 g), birth order (being the second-born), and difference in birth weights
      (>30% discordance). CONCLUSION: Twins were at an increased risk of stillbirth.
      Improved understanding of factors associated with stillbirth in this population
      could help to improve perinatal outcomes globally.

PMID- 25862295
TI  - [Near-infrared spectroscopy as an auxiliary tool in the study of child
      development].
AB  - OBJECTIVE: To investigate the applicability of Near-Infrared Spectroscopy (NIRS)
      for cortical hemodynamic assessment tool as an aid in the study of child
      development. DATA SOURCE: Search was conducted in the PubMed and Lilacs databases
      using the following keywords: "psychomotor performance/child development/growth
      and development/neurodevelopment/spectroscopy/near-infrared" and their
      equivalents in Portuguese and Spanish. The review was performed according to
      criteria established by Cochrane and search was limited to 2003 to 2013. English,
      Portuguese and Spanish were included in the search. DATA SYNTHESIS: Of the 484
      articles, 19 were selected: 17 cross-sectional and two longitudinal studies,
      published in non-Brazilian journals. The analyzed articles were grouped in
      functional and non-functional studies of child development. Functional studies
      addressed the object processing, social skills development, language and
      cognitive development. Non-functional studies discussed the relationship between
      cerebral oxygen saturation and neurological outcomes, and the comparison between
      the cortical hemodynamic response of preterm and term newborns. CONCLUSIONS: NIRS
      has become an increasingly feasible alternative and a potentially useful
      technique for studying functional activity of the infant brain.

PMID- 25862296
TI  - A gamut of undiscovered electrophysiological effects produced by Tityus
      serrulatus toxin 1 on NaV-type isoforms.
AB  - In the last decades, Ts1 has not only been the subject of many studies, it has
      also been considered as a very useful tool to investigate NaV channels and to
      explore the exact role of NaV channels in channelopathies. Ts1 is believed to
      modulate the activation process of NaV upon interaction at the neurotoxin binding
      site 4. Our aim was to carry out an in depth functional characterization of Ts1
      on a wide array of Nav channels, in order to investigate its mechanism of action
      and to verify if Ts1 can indeed be considered as a prototype site 4 selective
      toxin, valid for all the Nav isoforms we know currently. Ts1 has been subjected
      to an in-depth functional investigation on 9 NaV isoforms expressed in Xenopus
      laevis oocytes. Ts1 does not only interfere with the activation process but also
      modulates the inactivation in a bell-shaped voltage-dependent matter.
      Furthermore, Ts1 altered the ion selectivity through insect NaV. without
      influencing the tetrodotoxin selectivity of the channels. Finally, Ts1 was also
      found to inhibit the sodium current through the cardiac Nav1.5 isoform. On the
      basis of the totally unexpected plethora of Nav modulations as induced by Ts1, we
      demonstrate that caution is required in interpretation the in vivo experiments
      when using Ts1. The electrophysiological characterization of Ts1 indeed shows
      that the general accepted contours of NaV binding sites are much more obscure
      than believed and that interpretation of NaV pharmacology upon toxin binding is
      more complex than believed thus far.

PMID- 25862297
TI  - A randomized controlled trial to test the effect of multispecies probiotics on
      cognitive reactivity to sad mood.
AB  - BACKGROUND: Recent insights into the role of the human microbiota in cognitive
      and affective functioning have led to the hypothesis that probiotic
      supplementation may act as an adjuvant strategy to ameliorate or prevent
      depression. OBJECTIVE: Heightened cognitive reactivity to normal, transient
      changes in sad mood is an established marker of vulnerability to depression and
      is considered an important target for interventions. The present study aimed to
      test if a multispecies probiotic containing Bifidobacterium bifidum W23,
      Bifidobacterium lactis W52, Lactobacillus acidophilus W37, Lactobacillus brevis
      W63, Lactobacillus casei W56, Lactobacillus salivarius W24, and Lactococcus
      lactis (W19 and W58) may reduce cognitive reactivity in non-depressed
      individuals. DESIGN: In a triple-blind, placebo-controlled, randomized, pre- and
      post-intervention assessment design, 20 healthy participants without current mood
      disorder received a 4-week probiotic food-supplement intervention with the
      multispecies probiotics, while 20 control participants received an inert placebo
      for the same period. In the pre- and post-intervention assessment, cognitive
      reactivity to sad mood was assessed using the revised Leiden index of depression
      sensitivity scale. RESULTS: Compared to participants who received the placebo
      intervention, participants who received the 4-week multispecies probiotics
      intervention showed a significantly reduced overall cognitive reactivity to sad
      mood, which was largely accounted for by reduced rumination and aggressive
      thoughts. CONCLUSION: These results provide the first evidence that the intake of
      probiotics may help reduce negative thoughts associated with sad mood. Probiotics
      supplementation warrants further research as a potential preventive strategy for
      depression.

PMID- 25862298
TI  - Aggregation and antigenicity of virus like particle in salt solution--A case
      study with hepatitis B surface antigen.
AB  - The phenomenon of aggregation of virus-like particles (VLPs) in salt solution and
      the corresponding effect upon antigenicity was reported. Asymmetrical flow field
      flow fractionation (AF4) combined with multi-angle laser light scattering (MALLS)
      was used to characterize the size and the aggregation behavior of hepatitis B
      surface antigen (HBsAg). The average diameter of HBsAg VLP was 22.8+/-0.4 nm and
      it tended to aggregate in salt solution to form large particles and the
      antigenicity changed accordingly. In 0-4 M NaCl solution, part of HBsAg molecules
      aggregated rapidly into oligomeric particles (OP), whose diameter distributed
      from 25 to 40 nm, and the antigenicity slightly decreased about 10%. The
      aggregation reaction is reversible. After removing NaCl, both size and
      antigenicity could recover to normal level (92-96%). By contrast, the aggregation
      process is more complicated in (NH4)2SO4 solution. Most of HBsAg particles
      aggregated into OP and further aggregated into polymeric particles (PP). The
      diameter of the PP could reach 40 to 140 nm. The concentration of (NH4)2SO4 had
      remarkable influence upon the rate of aggregation. When concentration of
      (NH4)2SO4 was below 1 M, most of HBsAg aggregated only into OP in 1 h. While with
      concentration of (NH4)2SO4 above 1 M, most of particles formed PP within 1 h. The
      aggregation process to PP was irreversible. After removing (NH4)2SO4, the large
      aggregates could not recover to normal particles and the remaining antigenicity
      was below 30%.

PMID- 25862299
TI  - A randomized clinical trial in adults and newborns in South Africa to compare the
      safety and immunogenicity of bacille Calmette-Guerin (BCG) vaccine administration
      via a disposable-syringe jet injector to conventional technique with needle and
      syringe.
AB  - INTRODUCTION: Intradermal bacille Calmette-Guerin (BCG) vaccination by needle
      free, disposable-syringe jet injectors (DSJI) is an alternative to the Mantoux
      method using needle and syringe (NS). We compared the safety and immunogenicity
      of BCG administration via the DSJI and NS techniques in adults and newborn
      infants at the South African Tuberculosis Vaccine Initiative (SATVI) research
      site in South Africa. METHOD: Thirty adults and 66 newborn infants were
      randomized 1:1 to receive intradermal BCG vaccine (0.1 mL in adults; 0.05 mL in
      infants) via DSJI or NS. Wheal diameter (mm) and skin fluid deposition at the
      site of injection (SOI) were measured immediately post-vaccination. Adverse
      events and SOI reactogenicity data were collected 30 min and 1, 2, 4, and 12
      weeks after vaccination for adults and at 30 min and 4, 10, and 14 weeks for
      infants. Blood was collected in infants at 10 and 14 weeks to assess BCG-specific
      T-cell immune responses. RESULTS: More infant BCG vaccinations by DSJI deposited
      >5 MUL fluid on the skin surface, compared to NS (49% versus 9%, p=0.001).
      However, all 12 infant vaccinations that did not produce any SOI wheal occurred
      in the NS group (36%, p<0.001). Median wheal diameter, in participants for which
      an SOI wheal formed, did not differ significantly between groups in infants
      (combined 3.0mm IQR 2.0 to 4.0, p=0.59) or in adults (combined 9.0mm IQR 7.0 to
      10.0, p=0.13). Adverse events were similar between study arms. Proportion of
      participants with BCG scars after three months did not differ in adults (combined
      97%, p=0.67) or infants (combined 62%, p=0.13). Frequencies of BCG-specific
      clusters of differentiation 4 (CD4) and clusters of differentiation 8 (CD8) T
      cells co-expressing IFN-gamma, TNF-alpha, IL-2, and/or IL-17 were not different
      in the DSJI and NS groups. CONCLUSION: BCG vaccination of newborn infants via
      DSJI was more likely to deliver an appropriate intradermal wheal at the SOI as
      compared to NS, despite leaving more fluid on the surface of the skin. Safety,
      reactogenicity, and antigen-specific T-cell immune responses did not differ
      between DSJI and NS techniques.

PMID- 25862301
TI  - [Prof. Hans-Peter Heilmann on the occasion of his 80th birthday].

PMID- 25862300
TI  - An inactivated yellow fever 17DD vaccine cultivated in Vero cell cultures.
AB  - Yellow fever is an acute infectious disease caused by prototype virus of the
      genus Flavivirus. It is endemic in Africa and South America where it represents a
      serious public health problem causing epidemics of hemorrhagic fever with
      mortality rates ranging from 20% to 50%. There is no available antiviral therapy
      and vaccination is the primary method of disease control. Although the attenuated
      vaccines for yellow fever show safety and efficacy it became necessary to develop
      a new yellow fever vaccine due to the occurrence of rare serious adverse events,
      which include visceral and neurotropic diseases. The new inactivated vaccine
      should be safer and effective as the existing attenuated one. In the present
      study, the immunogenicity of an inactivated 17DD vaccine in C57BL/6 mice was
      evaluated. The yellow fever virus was produced by cultivation of Vero cells in
      bioreactors, inactivated with beta-propiolactone, and adsorbed to aluminum
      hydroxide (alum). Mice were inoculated with inactivated 17DD vaccine containing
      alum adjuvant and followed by intracerebral challenge with 17DD virus. The
      results showed that animals receiving 3 doses of the inactivated vaccine (2
      MUg/dose) with alum adjuvant had neutralizing antibody titers above the cut-off
      of PRNT50 (Plaque Reduction Neutralization Test). In addition, animals immunized
      with inactivated vaccine showed survival rate of 100% after the challenge as well
      as animals immunized with commercial attenuated 17DD vaccine.

PMID- 25862302
TI  - The Importance of Efficacy: Using the Extended Parallel Process Model to Examine
      Factors Related to Preschool-Age Children Enrolled in Medicaid Receiving
      Preventive Dental Visits.
AB  - Early preventive dental visits are vital to the oral health of children. Yet many
      children, especially preschool-age children enrolled in Medicaid, do not receive
      early visits. This study attempts to uncover factors that can be used to
      encourage parents to seek preventive dental care for preschool-age children
      enrolled in Medicaid. The extended parallel process model was used as a
      theoretical framework for this research. This model suggests that people will act
      if the perceived threat (severity and susceptibility) is high enough and if
      efficacy levels (self-efficacy and response efficacy) are likewise high.
      Following Witte's method of categorizing people's perceptions and emotions into
      one of four categories based on levels of threat and efficacy, this article
      describes four groups (high threat/high efficacy, high threat/low efficacy, low
      threat/high efficacy, and low threat/low efficacy) of parents and how they
      compare to each other. Using logistic regression to model if a child had a
      preventive visit, results indicate that parents with low threat/high efficacy and
      parents with high threat/high efficacy had approximately 2.5 times the odds of
      having a child with a preventive oral health visit compared to parents with low
      threat/low efficacy, when controlling for perceived oral health status, health
      literacy, and child's age. The importance of efficacy needs to be incorporated in
      interventions aimed at increasing preventive dental visits for young children. 

PMID- 25862303
TI  - Functionally divergent alleles and duplicated Loci encoding an acyltransferase
      contribute to acylsugar metabolite diversity in Solanum trichomes.
AB  - Glandular trichomes from tomato (Solanum lycopersicum) and other species in the
      Solanaceae produce and secrete a mixture of O-acylsugars (aliphatic esters of
      sucrose and glucose) that contribute to insect defense. Despite their
      phylogenetic distribution and diversity, relatively little is known about how
      these specialized metabolites are synthesized. Mass spectrometric profiling of
      acylsugars in the S. lycopersicum x Solanum pennellii introgression lines
      identified a chromosome 11 locus containing a cluster of BAHD acyltransferases
      with one gene (named Sl-ASAT3) expressed in tip cells of type I trichomes where
      acylsugars are made. Sl-ASAT3 was shown to encode an acyl-CoA-dependent
      acyltransferase that catalyzes the transfer of short (four to five carbons)
      branched acyl chains to the furanose ring of di-acylsucrose acceptors to produce
      tri-acylsucroses, which can be further acetylated by Sl-ASAT4 (previously Sl
      AT2). Among the wild tomatoes, diversity in furanose ring acyl chains on
      acylsucroses was most striking in Solanum habrochaites. S. habrochaites
      accessions from Ecuador and northern Peru produced acylsucroses with short (<=C5)
      or no acyl chains on the furanose ring. Accessions from central and southern Peru
      had the ability to add short or long (up to C12) acyl chains to the furanose
      ring. Multiple ASAT3-like sequences were found in most accessions, and their in
      vitro activities correlated with observed geographical diversity in acylsugar
      profiles. 

PMID- 25862304
TI  - PHOSPHATIDIC ACID PHOSPHOHYDROLASE Regulates Phosphatidylcholine Biosynthesis in
      Arabidopsis by Phosphatidic Acid-Mediated Activation of CTP:PHOSPHOCHOLINE
      CYTIDYLYLTRANSFERASE Activity.
AB  - Regulation of membrane lipid biosynthesis is critical for cell function. We
      previously reported that disruption of PHOSPHATIDIC ACID PHOSPHOHYDROLASE1 (PAH1)
      and PAH2 stimulates net phosphatidylcholine (PC) biosynthesis and proliferation
      of the endoplasmic reticulum (ER) in Arabidopsis thaliana. Here, we show that
      this response is caused specifically by a reduction in the catalytic activity of
      the protein and positively correlates with an accumulation of its substrate,
      phosphatidic acid (PA). The accumulation of PC in pah1 pah2 is suppressed by
      disruption of CTP:PHOSPHOCHOLINE CYTIDYLYLTRANSFERASE1 (CCT1), which encodes a
      key enzyme in the nucleotide pathway for PC biosynthesis. The activity of
      recombinant CCT1 is stimulated by lipid vesicles containing PA. Truncation of
      CCT1, to remove the predicted C-terminal amphipathic lipid binding domain,
      produced a constitutively active enzyme. Overexpression of native CCT1 in
      Arabidopsis has no significant effect on PC biosynthesis or ER morphology, but
      overexpression of the truncated constitutively active version largely replicates
      the pah1 pah2 phenotype. Our data establish that membrane homeostasis is
      regulated by lipid composition in Arabidopsis and reveal a mechanism through
      which the abundance of PA, mediated by PAH activity, modulates CCT activity to
      govern PC content. 

PMID- 25862305
TI  - Practices of end-of-life decisions in 66 southern French ICUs 4 years after an
      official legal framework: A 1-day audit.
AB  - OBJECTIVE: Since the implementation of two French laws in 2002 and 2005 and the
      implementation of guidelines about End-of-Life (EoL) decisions, few studies
      concerning EoL practices in French intensive care units (ICUs) have been
      reported. This study was aimed at assessing compliance with recommendations and
      current legislation concerning EoL decisions. METHOD: Prospective observational
      study based on 1-day audit conducted from January to May 2009 in 66 southern
      French ICUs. RESULTS: Six hundred and twenty-five patients were included (median
      age: 63 [52-76] years, median SAPS II: 46 [34-58]). The written designation of a
      surrogate decision-maker was reported for 87 (15%) patients. Advance directives
      were completed for only 4% of patients. The EoL decision-making process consisted
      in a multidisciplinary approach for 99 (47%) patients and was recorded in the
      medical chart for 63 (64%) cases. Families were informed about medical decisions
      in 58% of cases. This proportion was higher (87%) if a decision to forego life
      sustaining therapy was made. EoL decisions consisted of withholding treatments
      for 72 (94%) patients and withdrawal of treatments for 5 (6%) patients. In the
      multivariate stepwise logistic regression, four variables were independently
      associated with a decision to forego life support: preexisting dependence on
      others (P<0.0001), advance directives (P=0.01), age (P=0.008) and the SAPS 2
      score (P=0.009). CONCLUSION: The major finding of the present study is the
      existence of a gap between the widely approved EoL recommendations made by
      scientific societies and the daily practice of southern French ICUs. Even if EoL
      decisions are mostly shared with relatives, their written documentation in
      medical charts remains insufficient. Concerning EoL practices, the withdrawal of
      treatment remains an uncommon decision.

PMID- 25862306
TI  - Informing patients about limits to confidentiality: A qualitative study in
      prisons.
AB  - AIM: Confidentiality is important in healthcare practice, however, under certain
      circumstances, confidentiality is breached. In this paper, mental health
      professionals' (MHPs) practices related to informing imprisoned patients about
      confidentiality and its limits are presented. METHODS: Twenty-four MHPs working
      in Swiss prisons were interviewed. Data analysis involved qualitative thematic
      coding and was validated by discussing results with external experts and study
      participants. RESULTS: For expert evaluations and court-ordered therapies,
      participants informed patients that information revealed during these
      consultations is not bound by confidentiality rules. The practice of routinely
      informing patients about confidentiality and its limits became more complex in
      voluntary therapies, for which participants described four approaches and
      provided justifications in favour of or against their use. CONCLUSIONS: Further
      training and continued education are needed to improve physicians' ethical and
      legal knowledge about confidentiality disclosures. In order to promote ethical
      practices, it is important to understand and address existing motivations,
      attitudes and behaviours that impede appropriate patient information. Our study
      adds important new knowledge about the limits to confidentiality, particularly
      for providers working with vulnerable populations. Results from this study
      reflect typical ethical and practical dilemmas faced by and of interest to
      physicians working in forensic medicine and other related settings.

PMID- 25862307
TI  - Automated detection of effective left-ventricular pacing: going beyond percentage
      pacing counters.
AB  - AIMS: Cardiac resynchronization therapy (CRT) devices report percentage pacing as
      a diagnostic but cannot determine the effectiveness of each paced beat in
      capturing left-ventricular (LV) myocardium. Reasons for ineffective LV pacing
      include improper timing (i.e. pseudofusion) or inadequate pacing output. Device
      based determination of effective LV pacing may facilitate optimization of CRT
      response. METHODS AND RESULTS: Effective capture at the LV cathode results in a
      negative deflection (QS or QS-r morphology) on a unipolar electrogram (EGM).
      Morphological features of LV cathode-RV coil EGMs were analysed to develop a
      device-based automatic algorithm, which classified each paced beat as effective
      or ineffective LV pacing. The algorithm was validated using acute data from 28
      CRT-defibrillator patients. Effective LV pacing and pseudofusion was simulated by
      pacing at various AV delays. Loss of LV capture was simulated by RV-only pacing.
      The algorithm always classified LV or biventricular (BV) pacing with AV delays
      <=60% of patient's intrinsic AV delay as effective pacing. As AV delays
      increased, the percentage of beats classified as effective LV pacing decreased.
      Algorithm results were compared against a classification truth based on
      correlation coefficients between paced QRS complexes and intrinsic rhythm QRS
      templates from three surface ECG leads. An average correlation >0.9 defined a
      classification truth of ineffective pacing. Compared against the classification
      truth, the algorithm correctly classified 98.2% (3240/3300) effective LV pacing
      beats, 75.8% (561/740) of pseudofusion beats, and 100% (540/540) of beats with
      loss of LV capture. CONCLUSION: A device-based algorithm for beat-by-beat
      monitoring of effective LV pacing is feasible.

PMID- 25862308
TI  - The first comprehensive study of praziquantel effects in vivo and in vitro on
      European liver fluke Opisthorchis felineus (Trematoda).
AB  - The European liver fluke Opisthorchis felineus (Rivolta, 1884) is an
      epidemiologically important parasite infecting mammals, including humans.
      Opisthorchis felineus is widespread in Russia, Kazakhstan and Eastern European
      countries. Praziquantel (PZQ) is the drug of choice for the treatment of
      opisthorchiasis, but the effects of this drug on O. felineus are poorly studied.
      The aims of this work were (i) to perform a study of PZQ effects in vitro, (ii)
      to identify morphological markers of PZQ action on O. felineus, (iii) to analyse
      damage to the worm surface and (iv) to assess the efficacy of PZQ in vivo in a
      hamster model. Light microscopy, optical sectioning and fluorescence microscopy
      were used to study morphological changes. In vivo, PZQ at a dose of 400mg/kg
      reduced the rate of infection in experimental acute and chronic opisthorchiasis
      in hamsters by 70% and 79%, respectively. In vitro, the drug caused destruction
      and vacuolisation of the tegument of O. felineus, contractions of the worm
      musculature, paralysis, and irreversible changes in morphology (IC50=0.14MUg/mL).
      Differences in susceptibility to the drug between adult and newly excysted
      metacercariae were also observed. Qualitative effects of PZQ in vivo and in vitro
      were similar to the drug's effects on other trematodes, including
      epidemiologically important liver flukes. Nevertheless, high heterogeneity of O.
      felineus specimens in terms of susceptibility to the drug was observed. In
      addition, we describe for the first time the high rate of recovery of O. felineus
      following the destructive action of PZQ. 

PMID- 25862309
TI  - Does use of the polyene natamycin as a food preservative jeopardise the clinical
      efficacy of amphotericin B? A word of concern.
AB  - Natamycin is a poorly soluble, polyene macrolide antifungal agent used in the
      food industry for the surface treatment of cheese and sausages. This use is not
      of safety concern. However, highly soluble natamycin-cyclodextrin inclusion
      complexes have been developed for the protection of beverages. This practice
      leads to high drug exposures exceeding the safety level. Apart from the
      definition of an acceptable daily dietary exposure to natamycin, its effect on
      the faecal flora as a reservoir for resistance has to be examined. Consumption of
      food to which natamycin has been added and mixed homogeneously, such as yoghurt,
      and in particular the addition of cyclodextrin inclusion complexes to beverages
      and wine generates high faecal natamycin concentrations resulting in high drug
      exposures of faecal Candida spp. Development of natamycin resistance has been
      observed in Candida spp. colonising the intestinal tract of patients following
      natamycin treatment of fungal infections. Horizontal gene transfer among
      different Candida spp. and within Aspergillus fumigatus spreads resistance.
      Therefore, it cannot be denied that use of natamycin for preservation of yoghurt
      and beverages may foster development of resistance to polyenes in Candida spp. 

PMID- 25862310
TI  - Attachment relationships of adolescents who spent their infancy in residential
      group care: The Greek Metera study.
AB  - A prospective longitudinal study beginning whilst the infants were living in the
      Metera Babies Centre showed that the great majority showed a disorganized
      attachment during the period of residential care, even though neither
      abuse/neglect nor subnutrition were involved. There was an initial follow-up post
      adoption age at four years. This paper concerns a further follow-up of the 52
      adopted adolescents aged 13 years who had spent their first two years of life in
      Metera Babies Centre. They were compared to 36 adolescents reared in their
      biological families who, during their infancy, attended full-time public day
      care. The key aim was to examine continuities and discontinuities between early
      and contemporary relationships. The Child Attachment Interview was employed in
      adolescence. The main findings were a significant decrease in the rate of
      disorganization and a lack of a significant difference between the previously
      institutionalized group and the family care comparison group on attachment
      qualities in adolescence. There was not sufficient statistical power, however, to
      detect a small difference.

PMID- 25862311
TI  - Screening for extended-spectrum beta-lactamase-producing Enterobacteriaceae:
      where next?

PMID- 25862312
TI  - Disinfection of dynamic mattresses: highlighting an infection control issue.

PMID- 25862313
TI  - [Living environment and activation of early maladaptive schemas specific to the
      elderly: Comparative study among 80 individuals].
AB  - INTRODUCTION: Early maladaptive schemas described by Young may be identified in
      the elderly. They represent models and themes of emotions, memories, thoughts and
      bodily sensations experienced by the individual. This study aims to evaluate the
      activation of early maladaptive thoughts in the elderly depending on their living
      environment. METHODS: The Young Schema Questionnaire--short form--was
      administered to 80 elderly individuals (40 living in a nursing home, and 40 in
      their own home with at least one person). The studied schemas that were most
      relevant to the elderly were the maladaptive schemas of abandonment, emotional
      deprivation, mistrust, exclusion, dependency, vulnerability and emotional
      overcontrol. The Mini-Mental State Examination (MMSE) and the Geriatric
      Depression Scale were administered to eliminate dementia or depression among
      individuals. RESULTS: Individuals living in a nursing home, compared to their
      controls had increased activation of schemas of emotional deprivation (22.5% vs.
      7.5%), abandonment (15% vs. 0%), mistrust (32.5% vs. 2.5%), exclusion (7.5% vs.
      0%), and emotional overcontrol (25% vs. 2.5%). The activation of maladaptive
      schemas was significantly elevated in nursing homes for those 5 schemas, while
      there was no difference in activation between the 2 groups concerning the schemas
      of dependency and vulnerability. DISCUSSION: The activation of early maladaptive
      schemas of emotional deprivation, abandonment, mistrust, exclusion, and emotional
      overcontrol is higher in individuals living in nursing homes compared to a
      control group of individuals living in their homes with at least one companion.
      This schema activation may be related to a lack of emotional and family support
      in the elderly.

PMID- 25862314
TI  - The sharp decline of beta estrogen receptors expression in long-lasting
      ulcerative-associated carcinoma.
AB  - OBJECTIVE: Colorectal carcinoma is an important cause of death in inflammatory
      bowel diseases, thus requiring surveillance for dysplasia in long-standing
      ulcerative colitis (UC). Females show a lower incidence probably related to
      hormonal factors; therefore, a role of estrogen receptors (ERs) has been supposed
      in carcinoma-associated colitis (CAC) development. Our aim was to identify ER
      beta/alpha expression in long-lasting pancolitis through each grade of dysplasia
      to carcinoma and, furthermore, to investigate the simultaneous epithelial
      apoptosis/proliferation. MATERIALS AND METHODS: Forty-eight patients affected by
      long-lasting pancolitis were retrospectively investigated. Samples were divided
      into four groups: UC, low-grade dysplasia/high-grade dysplasia (UC-HGD), and CAC.
      Normal colon samples were used as controls. ER-beta, ER-alpha, Ki-67, and TUNEL
      expression (labeling/H index) were evaluated by immunohistochemistry. RESULTS: ER
      beta expression revealed an impressive reduction in CAC (10.4 +/- 5.1; p < 0.001)
      compared to controls and UC (34.3 +/- 3.1 and 26.8 +/- 7.8, respectively),
      meanwhile ER-beta level in LGD (29.4 +/- 3.7) was comparable to UC. As far ER
      beta/ER-alpha mean value ratio revealed a progressive reduction. Ki67
      demonstrated a progressive significant increase from UC until CAC (37.9 +/- 6.4 <
      45.7 +/- 6.2 < 60.6 +/- 5.2 < 71.1 +/- 5.1; p < 0.001). Apoptotic index (TUNEL)
      revealed a strong fall in UC-HGD and CAC. CONCLUSIONS: ER-beta fall could be
      considered as a biomarker of UC-dysplasia progression. It occurs in HGD and overt
      neoplasia, while in LGD shows a normal expression. At the moment, we are unable
      to use this tool in the clinical practice to predict tumor progression, but it
      would be appropriate to encourage ER expression investigations in large samples
      for the interesting perspectives of application.

PMID- 25862315
TI  - Coloured filters to reduce the symptoms of visual stress in children with reading
      delay--PHILIP G. GRIFFITHS.

PMID- 25862316
TI  - Coronary sinus and another sinus: which one to cannulate?

PMID- 25862317
TI  - A long-term study of the impulsive choices of Lewis and Fischer 344 rats.
AB  - Contemporary analyses of choice were implemented to analyze the acquisition and
      maintenance of response allocation in Lewis (LEW) and Fischer 344 (F344) rats. A
      concurrent-chains procedure varied the delay to the larger reinforcer (0.1, 5,
      10, 20, 40, and 80 s). Delays were presented within sessions in ascending,
      descending, and random orders. Each condition lasted 105 days, and the entire
      data set was analyzed to obtain discounting functions for each block of 15
      sessions and each food delivery across delay components. Both a hyperbolic-decay
      model and the generalized matching law described well the choices of LEW and F344
      rats. Estimates of discounting rate and sensitivity to the immediacy of
      reinforcement correlated positively. The slope of the discounting function
      changed with presentation orders of the delays to the larger reinforcer. Extended
      training reduced differences between the LEW and F344 rats in discounting rates,
      sensitivity to the immediacy of reinforcement, and estimates of the area under
      the curve. We concluded that impulsive choice can change as a function of
      learning and is not a static property of behavior that is mainly determined by
      genetic and neurochemical mechanisms. Choosing impulsively may be an advantage
      for organisms searching for food in rapidly changing environments.

PMID- 25862318
TI  - Rarity of late anastomotic leakage after low anterior resection of the rectum.
AB  - BACKGROUND: Late anastomotic leakage is reported to account for half of all
      anastomotic leakages after low anterior resection of the rectum. An important
      clinical question is whether late and early anastomotic leakages are different
      entities. METHODS: We retrospectively reviewed the medical records of patients
      who experienced anastomotic leakage after low anterior resection in two Japanese
      hospitals. The clinical characteristics were extracted and analyzed. RESULTS:
      During the study period, 179 patients underwent low anterior resection. A pelvic
      drainage tube was routinely utilized in all cases and was generally removed 4 to
      6 days after the operation. Twenty-six patients had anastomotic leakage; the
      diagnosis was based on fecal contamination of the drainage in 24 cases. The
      median interval between operation and detection of anastomotic leakage was 3.5
      days. Anastomotic leakage was diagnosed within 7 days of the operation in 25
      cases and on postoperative day 20 (after hospital discharge) in one case. There
      was no instance of anastomotic leakage diagnosed more than 30 days after the
      operation. There was no relationship between clinical variables and days of
      leakage diagnosis. CONCLUSION: The rarity of late anastomotic leakage in our
      study, compared with previous studies, may relate to the relatively extended
      period of pelvic drainage tube usage in our institutes, which likely shortens the
      interval before leakage diagnosis. Our results suggest that late anastomotic
      leakage is a delayed symptom of subtle early anastomotic leakage rather than a
      separate entity.

PMID- 25862319
TI  - Age, Comorbidity, and the Risk of Prostate Cancer-Specific Mortality in Men With
      Biopsy Gleason Score 4+3: Implications on Patient Selection for Multiparametric
      MRI.
AB  - BACKGROUND: Some men with biopsy Gleason score (GS) 7 prostate cancer (PC) harbor
      occult GS 8 to 10 PC and might be undertreated with short-term androgen
      deprivation therapy (ADT) and radiation therapy (RT). With advancing age
      associated with occult high-grade PC, we evaluated PC-specific mortality (PCSM)
      risk after RT and short-term ADT for older men with GS 4+3 PC and men of any age
      with GS 8 to 10 PC. PATIENTS AND METHODS: The study cohort comprised 206 men with
      unfavorable-risk PC treated with RT or RT and 6 months of ADT on a randomized
      trial between 1995 and 2001. Competing risks regression was used to compare PCSM
      risk for men with GS 8 to 10 PC to men with GS <= 3+4, GS 4+3 and age <= 73 years
      (median age), and GS 4+3 and age > 73 years, adjusting for PC risk factors,
      comorbidity, and treatment. RESULTS: After a median follow-up of 14.3 years, 135
      men died (65.53%), 24 (17.78%) of PC. Men age > 73 years with GS 4+3 PC did not
      have significantly lower PCSM risk compared with men with GS 8 to 10 (adjusted
      hazard ratio [AHR], 1.08; 95% confidence interval [CI], 0.29-4.06; P = .91);
      whereas unhealthy men (AHR, 0.20; 95% CI, 0.04-0.93; P = .04) and men age <= 73
      years with GS 4+3 (AHR, 0.09; 95% CI, 0.01-1.03; P = .05) fared better.
      CONCLUSION: Men age > 73 years with biopsy GS 4+3 did not have a significant
      difference in PCSM risk than men with GS 8 to 10, supporting further study of
      multiparametric magnetic resonance imaging in such men with no or minimal
      comorbidity before determining ADT duration.

PMID- 25862320
TI  - Greatest Percentage Involved Core Length and Risk of Clinically Significant
      Prostate-Specific Antigen Failure After Radical Prostatectomy.
AB  - BACKGROUND: Radical prostatectomy (RP) can cure men with unfavorable intermediate
      or high-risk prostate cancer (PC). However, some will experience short prostate
      specific antigen (PSA) doubling time (PSADT) failure that requires additional
      treatment with increased toxicity. The present study investigated whether the
      greatest percentage of involved biopsy core length (GPC) can preoperatively
      identify men at risk of short PSADT failure. PATIENTS AND METHODS: A total of 503
      men with biopsy-proven PC underwent RP at an academic institution from January
      2005 to December 2008. Men with incomplete pathologic information, those who had
      received neoadjuvant or adjuvant hormonal therapy or chemotherapy, and those who
      had undergone adjuvant radiation therapy were excluded. The median follow-up
      period was 4.89 years (interquartile range, 1.97-5.68 years). A competing risk
      regression was used to assess whether an increasing GPC value was associated with
      an increased PSADT at < 10-month failure risk, adjusting for age, percentage of
      positive biopsy results, and risk group. RESULTS: Of the 402 men, 34 (8.46%)
      developed PSA failure, 17 (50.0%) of whom had a PSADT of < 10 months. An
      increasing GPC value was significantly associated with an increased PSADT of < 10
      month failure risk (adjusted hazard ratio, 1.03; 95% confidence interval, 1.01
      1.06; P = .015). Men with a GPC > 30% (median) versus <= 30% and unfavorable
      intermediate- or high-risk PC (P = .011), but not low or favorable intermediate
      risk PC (P = .57), had a significantly greater incidence of PSADT < 10-month
      failure estimates (30% vs. 0% at 5 years). CONCLUSION: Men planning to undergo RP
      for unfavorable intermediate- or high-risk PC with a GPC of > 30% should be
      considered for randomized trials evaluating the effect on survival of the
      neoadjuvant use of treatment that extends survival in those with castrate
      resistant metastatic PC.

PMID- 25862321
TI  - Robot-Assisted Laparoscopic Vesiculectomy for Large Seminal Vesicle Cystadenoma:
      A Case Report and Review of the Literature.

PMID- 25862323
TI  - [Milk and milk products: food sources of calcium].
AB  - The importance of calcium in human nutrition, the mechanisms of absorption and
      excretion of the element, and the factors affecting them with special reference
      to dietary factors are described. After reviewing daily dietary intakes of
      calcium and the main contributors in European and Spanish population, recommended
      intakes in Spain, the Nordic countries and the United States are mentioned. In
      relation to the dietary sources of calcium it has to be noted that the value of a
      given food as a source of a nutrient depends on its content in the food, the
      bioavailability of the nutrient and the usual food consumption. The calcium
      contents of potential food sources of the element are reported and its value is
      estimated according to the potential absorbability of the calcium they contain.
      The benefits of milk and dairy products as sources of calcium are also
      highlighted. Populations such as children or elderly may require fortified foods
      or supplements to satisfy their high calcium needs, so some examples of the
      efficacy of this supplementation are discussed. It is concluded that food and
      drinks are the best choice to obtain calcium. Taking into account the calcium
      content, the usual portion size and the consumption habits milk and dairy
      products, nuts, green leafy vegetables and legumes can provide adequate amounts
      of calcium. However, milk and dairy products constitute the best dietary source
      thanks to the bioavailability of the calcium they contain. 

PMID- 25862324
TI  - [Calcium and health].
AB  - An adequate intake of calcium is only not limited to avoid the risk of
      osteoporosis and its benefits in longterm bone health, but also it has been
      linked to protection against various major diseases, such as hypertension,
      cancer, kidney stones, insulin resistance, diabetes... and several investigations
      suggest its importance in preventing and controlling obesity. Studies conducted
      in Spanish representative samples show that a high percentage of adults and
      children (> 75%) don't achieve the recommended intake of calcium. Moreover, are
      growing trends among the population suggesting that calcium intake and dairy
      consumption (main food source of the mineral) are high, and even excessive, in
      many individuals. This misconception results in that the calcium intake is
      increasingly far from the recommended one. The maximum tolerable intake of the
      mineral is fixed at 2.500 mg/day, but this intake is unusual, and it's more
      disturbing and frequent, to find intakes below the recommended calcium intakes
      (1.000 and 1.200 mg/day in adults, men and women, respectively). Data from
      different studies highlight the risk of an inadequate calcium intake and the
      damages that may affect the health in a long term. It is not about transmitting
      indiscriminate guidelines in order to increase the intake of calcium / dairy, but
      the recommended intakes must be met to achieve both the nutritional and health
      benefits. Also activities for demystification of misconceptions are need,
      increasingly frequent, that may impair health population. 

PMID- 25862322
TI  - Elevating the Horizon: Emerging Molecular and Genomic Targets in the Treatment of
      Advanced Urothelial Carcinoma.
AB  - Despite recent advances in the identification of genomic alterations that lead to
      urothelial oncogenesis in vitro, patients with advanced urothelial carcinomas
      continue to have poor clinical outcomes. In the present review, we focus on
      targeted therapies that have yielded the most promising results alone or combined
      with traditional chemotherapy, including the antiangiogenesis agent bevacizumab,
      the human epidermal growth factor receptor 2 antibody trastuzumab, and the
      tyrosine kinase inhibitor cabozantinib. We also describe ongoing and developing
      clinical trials that use innovative approaches, including dose-dense scheduling
      of singular chemotherapy combinations, prospective screening of tumor tissues for
      mutational targets and biomarkers to predict chemosensitivity before the
      determination of the therapeutic regimen, and novel agents that target proteins
      in the immune checkpoint regulation pathway (programmed cell death protein 1 [PD
      1] and anti-PD-ligand 1) that have shown significant potential in preclinical
      models and early clinical trials. New agents and targeted therapies, alone or
      combined with traditional chemotherapy, will only be validated through accrual to
      developing clinical trials that aim to translate these therapies into
      individualized treatments and improved survival rates in urothelial carcinoma.

PMID- 25862325
TI  - [Vitamin D, determinant of bone and extrabone health. Importance of vitamin D
      supplementation in milk and dairy products].
AB  - Vitamin D is obtained mainly from ultraviolet irradiation of 7-dehydrocholesterol
      in the skin to form cholecalciferol (vitamin D3), and minimally from diet, unless
      vitamin D fortified food is taken, mainly enriched milk. In some countries,
      vitamin D is added to diet as ergocalciferol (vitamin D2). In the liver, vitamin
      D3 is hydroxylated to form 25-hydroxyvitamin D3 (marker of body nutritional
      status of vitamin D). Subsequently, in the kidney, 25OHD3 is hydroxylated to form
      1,25-dihydroxyvitamin D3 (1,25(OH)2D3). By VDR stimulation, (1,25)OH)2D3 controls
      calcium homeostasis and bone health and, what is more, many other cells and
      tissues including skin, muscle, cardiovascular and immune systems as well as
      glucose homeostasis. Thus, about 3% of the human genome is regulated by this
      hormone. Association and recent intervention studies describe beneficial effects
      on bone, cardiovascular disease, hypertension, diabetes mellitus type
      2,colorectal cancer, breast cancer, multiple sclerosis, immune function
      inflammation etc. A minimum target for public health should be to achieve serum
      25OHD levels above 20 ng/ml to ensure optimum status for bone health. However,
      levels above 30 ng/ml should be reached to achieve other health goals.
      Paradoxically, inadequacy (or even deficiency) in vitamin D levels is highly
      prevalent in children and youth in Spain. This deficit persists in adults, as
      well as in postmenopausal women (osteoporotic or not) and the elderly (especially
      amongst those institutionalized). Seasonal variation barely normalizes serum
      25OHD levels after summer-autumn. Treated postmenopausal osteoporotic women also
      show high prevalence of inadequate levels of vitamin D, a major contributor to
      antiresortive treatments failure. A normalization of serum vitamin D enables diet
      to provide the calcium necessary to achieve a good bone health and an adequate
      response to antiresortive drugs. Given the difficulty to get adequate levels of
      vitamin D by UV irradiation and diet, a proper supplementation of milk with
      vitamin D is an attractive chance and a challenge for Public Health of Spain and
      the European Union. It has provided excellent results in the US, Canada, Northern
      Europe Countries, etc. 

PMID- 25862326
TI  - [The nutrients of the milk on cardiovascular health].
AB  - The incidence of milk components on cardiovascular health is reviewed. A fraction
      of great interest in relation to cardiovascular disease is that of minerals,
      especially calcium. Benefits of milk in reducing blood pressure due to
      bioavailable calcium, along with other mineral elements present and bioactive
      peptides with antihypertensive ability, ACE inhibitors (key enzyme involved in
      the regulation of blood pressure) have been documented. Furthermore, a positive
      association of diets with high levels of calcium from milk, the fecal excretion
      of fat--which is favored by the same--and cardiovascular markers has also been
      reported. The presence in the milk of the essential, linoleic, linolenic and
      arachidonic fatty acids, although at low levels, is particularly interesting.
      Moreover, in the milk fat bioactive components as conjugated linoleic acid and
      sphingomyelin, which could exert potential cardioprotective effects are also
      present. However, because it contains high levels of saturated fatty acids, milk
      fat products consumption has been discouraged indiscriminately. According to the
      evidence collected in a long series of scientific studies it can be concluded
      that consumption of milk/dairy balanced and low-fat could be neutral effect or be
      inversely associated with cardiovascular risk.

PMID- 25862327
TI  - [Milk and food security].
AB  - In the history of food security in the EU there is a before and after the White
      Paper published in January 2000; since then we are witnessing radical new
      approaches in the Commission strategy to ensure the highest standards of food
      safety for EU citizens, based on a more coordinated and integrated organization.
      The basic principle was to extend the application of control measures at all
      stages of the production chain, which was summarized in the slogan which has
      since been repeated regularly: 'From Farm to Consumer'. The new guidelines for
      action were the answer to a series of food crises (dioxin, hormones, BSE...) that
      called into question the European agri-food system and, what was even more
      severe, produced a deep distrust of consumers by health risks attached to
      feeding. Beef and cow's milk, two basic components of the European diet, were the
      products most affected by the aforementioned crisis, which showed that in those
      years very few companies paid attention to the quality from the source. In this
      paper a review of the issues presented at the time, the measures implemented by
      the White Paper and the path travelled is done, while it raised the need to use
      safe and quality raw materials, so that consumers have absolute confidence in
      their food. 

PMID- 25862328
TI  - Patient-reported disability in the general Japanese population was associated
      with medical care visits for low back pain, regardless of pain intensity.
AB  - BACKGROUND: Race/ethnicity is known to affect pain severity and the emotional
      aspects of pain, with medical care visits also reported to differ according to
      race/ethnicity. It has been hypothesized that there is an interactive
      relationship between pain intensity and patient-reported disability and that the
      interactive relationships are related to medical care visits. However, it remains
      unclear whether the association between patient-reported disability and medical
      care visits for low back pain (LBP) are dependent on the pain intensity. The aims
      of this study were to examine the prevalence of medical care visits among members
      of the Japanese general population and to analyze the association between patient
      reported disability and medical care visits for LBP patients, regardless of the
      pain intensity. METHODS: From a random sample of the general Japanese population
      (n = 2962), we focused on those who experienced LBP within the past month.
      Subjects were asked about the number of medical care visits (medical clinic or
      complementary/alternative medical clinic) for LBP. Patient-reported disability
      was assessed using the Roland-Morris disability questionnaire (RDQ). Pain
      intensity of LBP was assessed by visual analog scale. To examine the association
      between RDQ and medical care visits among people with LBP, we used multiple
      logistic regression analysis and the trend analysis for the RDQ. RESULTS: Of 841
      reporting LBP in the past month, 285 (33.9 %) visited a medical care facility.
      After adjusting for pain intensity and other confounding factors, the odds ratios
      for the RDQ categories 1-5, 6-10, 11-15, and >= 16 were compared with the RDQ
      categories 0, 1.13 (95 % CI 0.73-1.73), 2.05 (95 % CI 1.17-3.60), 2.21 (95 % CI
      1.06-4.62), and 4.0 (95 % CI 1.60-9.98), respectively (p for trend <0.01).
      CONCLUSIONS: Patient-reported disability was associated with medical care visits
      for LBP, regardless of the pain intensity, with the results similar to those
      obtained for other races/ethnicities.

PMID- 25862329
TI  - Liraglutide Promotes Cortical Neurite Outgrowth via the MEK-ERK Pathway.
AB  - Liraglutide is the glucagon-like peptide-1 (GLP-1) synthetic form which has been
      approved by the US Food and Drug Administration to be released onto the market.
      The metabolic benefits of incretin hormone as an anti-diabetic agent are widely
      recognized, but its potential extra-pancreatic effects of GLP-1 analog
      (liraglutide) in the central nerve system are less well known. To this purpose,
      we used immunofluorescence method to examine the effect of liraglutide on neurite
      outgrowth in primary cortical neuron culture by measuring neurite length and
      confirmed the promotion effect. Then, we investigated the potential mechanisms
      and found that liraglutide promoted neurite outgrowth in a dose-dependant manner,
      and this effect could be partially inhibited by MEK-ERK inhibitor U0126. Besides,
      liraglutide induced an increase of p-ERK/ERK expression, which could be blocked
      in the presence of U0126. Similarly, phosphorylated transcription factor (p-CREB)
      level shared the same trend with p-ERK/ERK ratio after liraglutide treatment.
      Collectively, our data illustrated that that liraglutide exerts neurotrophin-like
      activity partly via MEK-ERK pathway, which might offer a novel idea for treatment
      of axon-associated neurological diseases. 

PMID- 25862330
TI  - The Dynamical Structure of HR 8799's Inner Debris Disk.
AB  - The HR 8799 system, with its four giant planets and two debris belts, has an
      architecture closely mirroring that of our Solar system where the inner, warm
      asteroid belt and outer, cool Edgeworth-Kuiper belt bracket the giant planets. As
      such, it is a valuable laboratory for examining exoplanetary dynamics and debris
      disk-exoplanet interactions. Whilst the outer debris belt of HR 8799 has been
      well resolved by previous observations, the spatial extent of the inner disk
      remains unknown. This leaves a significant question mark over both the location
      of the planetesimals responsible for producing the belt's visible dust and the
      physical properties of those grains. We have performed the most extensive
      simulations to date of the inner, unresolved debris belt around HR 8799, using
      UNSW Australia's Katana supercomputing facility to follow the dynamical evolution
      of a model inner disk comprising 300,298 particles for a period of 60 Ma. These
      simulations have enabled the characterisation of the extent and structure of the
      inner disk in detail, and will in future allow us to provide a first estimate of
      the small-body impact rate and water delivery prospects for possible (as-yet
      undetected) terrestrial planet (s) in the inner system. 

PMID- 25862331
TI  - In vitro antioxidant and hepatoprotective potential of Azolla microphylla
      phytochemically synthesized gold nanoparticles on acetaminophen - induced
      hepatocyte damage in Cyprinus carpio L.
AB  - The present study aims to evaluate the hepatoprotective and antioxidant effects
      of gold nanoparticles (GNaP) biosynthesized through the mediation of Azolla
      microphylla and A. microphylla extract on acetaminophen-induced hepatocyte damage
      in common carp fish (Cyprinus carpio L.). The gold nanoparticles (100, 150, 200
      MUg/ml) and A. microphylla extract powder (100, 200, 400 MUg/ml) were added to
      the primary hepatocytes in different conditions: treatment I (before 12 mM
      acetaminophen), treatment II (after 12 mM acetaminophen), and treatment III (both
      before and after 12 mM acetaminophen), and incubated. Among these, control group
      treated with 12 mM acetaminophen produced significantly elevated levels (50-80%)
      of lactate dehydrogenase (LDH), catalase (CAT), glutamate oxalate transaminase
      (GOT), glutamate pyruvate transaminase (GPT), and malondialdehyde (MDA), and
      significantly decreased the levels (60-75%) of superoxide dismutase (SOD) and
      glutathione peroxidase (GSH-Px). Treatment with methanol extract of A.
      microphylla phytochemically biosynthesized gold nanoparticles (100, 150, 200
      MUg/ml) and A. microphylla methanol extract powder (100, 200, 400 MUg/ml)
      significantly improved the viability of cells in a culture medium. It also
      significantly reduced the levels of LDH, CAT, GOT, GPT, and MDA, and
      significantly increased the levels of SOD and GSH-Px. In conclusion, gold
      nanoparticles biosynthesized through A. microphylla demonstrated effective
      hepatoprotective and antioxidant effects than methanol extract of A. microphylla.

PMID- 25862332
TI  - Effects of particle uptake, encapsulation, and localization in cancer cells on
      intracellular applications.
AB  - Endocytosis is a normal process in living cells, often used to internalize drug
      containing particles and probes for intracellular mechanics. The cell type, and
      especially malignancy, may affect particle internalization and transport.
      Specifically, membrane-encapsulation following internalization can affect
      particle interaction with the cell interior. Hence, particle-tracking
      measurements that reveal intracellular mechanics and dynamics require
      determination of effects of encapsulation. Here, we compare closely related,
      breast-cancer cell lines with high- and low-metastatic potential (MP) and benign,
      control cells. We evaluate time-dependent particle internalization, localization
      with endocytotic-pathway organelles, and membrane encapsulation at 2, 6, 24, and
      48 h after initial cell exposure to particles. High MP cells internalize
      particles more rapidly and in larger amounts than low MP and benign cells.
      Moreover, while only cells at the edge of two-dimensional colonies of benign
      cells internalized particles, all cancer cells uniformly internalize particles.
      Particles mostly colocalize with late endosomes (>80%), yet surprisingly, overall
      membrane encapsulation decreases with time, indicating release into the
      cytoplasm; encapsulation at 48 h is <35% in all three cell types. We discuss
      implications to drug delivery and show that encapsulation does not significantly
      affect intracellular particle-tracking experiments, showing the applicability of
      endocytosis. 

PMID- 25862333
TI  - High energy spectrogram with integrated prior knowledge for EMG-based locomotion
      classification.
AB  - Electromyogram (EMG) signal representation is crucial in classification
      applications specific to locomotion and transitions. For a given signal,
      classification can be performed using discriminant functions or if-else rule
      sets, using learning algorithms derived from training examples. In the present
      work, a spectrogram based approach was developed to classify (EMG) signals for
      locomotion mode. Spectrograms for each muscle were calculated and summed to
      develop a histogram. If-else rules were used to classify test data based on a
      matching score. Prior knowledge of locomotion type reduced class space to
      exclusive locomotion modes. The EMG data were collected from seven leg muscles in
      a sample of able-bodied subjects while walking over ground (W), ascending stairs
      (SA) and the transition between (W-SA). Three muscles with least discriminating
      power were removed from the original data set to examine the effect on
      classification accuracy. Initial classification error was <20% across all modes,
      using leave one out cross validation. Use of prior knowledge reduced the average
      classification error to <11%. Removing three EMG channels decreased the
      classification accuracy by 10.8%, 24.3%, and 8.1% for W, W-SA, and SA
      respectively, and reduced computation time by 42.8%. This approach may be useful
      in the control of multi-mode assistive devices. 

PMID- 25862334
TI  - Ethical guidelines for Sami research: the issue that disappeared from the
      Norwegian Sami Parliament's agenda?
AB  - BACKGROUND: In recent decades many indigenous communities, policy makers and
      researchers worldwide have criticized the academic community for not being aware
      of the specific challenges these communities have faced and still are facing with
      regard to research. One result of the decades of discourse in indigenous
      communities is the development in many Western countries of indigenously
      sensitive ethical research guidelines. In 1997 the Sami Parliament (SP) in Norway
      reached a unanimous decision that ethical guidelines for Sami research had to be
      drawn up. Such guidelines are however still to be created. OBJECTIVES: The
      objectives of this article are to enquire into what happened to the Norwegian
      SP's decision of 1997 and to reflect on why the issue seems to have disappeared
      from the SP's agenda. Finally, we consider whether research ethics is to be a
      subject for the research community only. METHODS: A review of parliamentary white
      papers on research and SP documents relating to research ethics. FINDINGS: The
      response to the SP's decision in 1997 took place in two different channels, both
      of them national, namely the research ethics channel and the political channel.
      Thus, there were actually two parallel processes taking place. In spite of nearly
      two decades of reports, the concept of the participation of indigenous
      communities in research is still not an integral part of Norwegian ethical
      guidelines. CONCLUSIONS: The issue of indigenously sensitive research ethics
      seems to have disappeared from the SP's agenda and the research ethics review
      system with regard to Sami research is with minor adjustments the same as when
      the SP asked for a revision.

PMID- 25862335
TI  - Meta-analysis of the association between plasminogen activator inhibitor-1 4G/5G
      polymorphism and recurrent pregnancy loss.
AB  - BACKGROUND: The association between plasminogen activator inhibitor-1 (PAI-1)
      4G/5G polymorphism and recurrent pregnancy loss (RPL) risk is still
      contradictory. We thus performed a meta-analysis. MATERIAL AND METHODS: Relevant
      studies were searched for in PubMed, Web of Science, Embase, and Cochrane
      Library. An odds ratio (OR) with a 95% confidence interval (CI) was used to
      assess the association between PAI-1 4G/5G polymorphism and RPL risk. RESULTS: A
      total of 22 studies with 4306 cases and 3076 controls were included in this meta
      analysis. We found that PAI-1 4G/5G polymorphism was significantly associated
      with an increased RPL risk (OR=1.89; 95% CI 1.34-2.67; P=0.0003). In the subgroup
      analysis by race, PAI-1 4G/5G polymorphism was significantly associated with an
      increased RPL risk in Caucasians (OR=2.23; 95% CI 1.44-3.46; P=0.0003). However,
      no significant association was observed in Asians (OR=1.47; 95% CI 0.84-2.59;
      P=0.18). CONCLUSIONS: In conclusion, this meta-analysis suggests that PAI-1 4G/5G
      polymorphism might be associated with RPL development in Caucasians.

PMID- 25862336
TI  - Perineural spread in pelvic malignancies can be an alternate explanation for
      pelvic bony metastases rather than hematogenous spread. A report of two cases.
AB  - We propose that pelvic malignancies can spread to bone and cause bony metastases
      using nerves as conduits. We reviewed two cases of pelvic malignancy with
      perineural spread of bladder cancer and prostate cancer. In a patient with
      prostate cancer, we identified six lesions that were positive on the (11)C
      choline PET/CT scan and MRI; in a patient with bladder cancer, we identified two
      lesions positive on the (18)F-deoxy-glucose PET/CT scan and MRI. We carefully
      reviewed the imaging studies, and using established sclerotome maps we identified
      spinal nerves supplying each of eight pelvic bony lesions. All these spinal
      nerves showed evidence of tumor infiltration with extension toward the affected
      bones. We theorize that perineural tumor spread may serve as an additional
      mechanism of pelvic osseous metastases in pelvic malignancies. 

PMID- 25862337
TI  - Paget's sarcoma of the patella.
AB  - Paget's sarcoma is a rare complication of Paget's disease and isolated Paget's
      disease of the patella is extremely rare. We describe a unique case of Paget's
      sarcoma of the patella in a 69-year-old male farmer who had a remote history of a
      fracture in the same patella 40 years previously. In this case, imaging and
      pathogenesis of Paget's disease of bone is described and factors implicated in
      the development of Paget's disease in this patient are evaluated. 

PMID- 25862338
TI  - Inner resources for survival: integrating interpersonal psychotherapy with
      spiritual visualization with homeless youth.
AB  - Homeless youth have particular need to develop inner resources to confront the
      stress, abusive environment of street life, and the paucity of external
      resources. Research suggests that treatment supporting spiritual awareness and
      growth may create a foundation for coping, relationships, and negotiating styles
      to mitigate distress. The current pilot study tests the feasibility,
      acceptability, and helpfulness of an interpersonal spiritual group psychotherapy,
      interpersonal psychotherapy (IPT) integrated with spiritual visualization (SV),
      offered through a homeless shelter, toward improving interpersonal coping and
      ameliorating symptoms of depression, distress, and anxiety in homeless youth. An
      exploratory pilot of integrative group psychotherapy (IPT + SV) for homeless
      young adults was conducted in a New York City on the residential floor of a
      shelter-based transitional living program. Thirteen young adult men (mean age
      20.3 years, SD = 1.06) participated in a weekly evening psychotherapy group (55 %
      African-American, 18 % biracial, 18 % Hispanic, 9 % Caucasian). Measures of
      psychological functioning were assessed at pre-intervention and post-intervention
      using the General Health Questionnaire (GHQ-12), Patient Health Questionnaire
      (PHQ-9, GAD-7), and the Inventory of Interpersonal Problems (IIP-32). A semi
      structured exit interview and a treatment satisfaction questionnaire were also
      employed to assess acceptability following treatment. Among homeless young adults
      to participate in the group treatment, significant decreases in symptoms of
      general distress and depression were found between baseline and termination of
      treatment, and at the level of a trend, improvement in overall interpersonal
      functioning and levels of general anxiety. High utilization and treatment
      satisfaction showed the intervention to be both feasible and acceptable. Offered
      as an adjunct to the services-as-usual model at homeless shelters serving young
      adults, interpersonal psychotherapy with spiritual visualization (IPT + SV) in
      group appears to be a feasible and potentially useful treatment option for
      promoting improved mental health. 

PMID- 25862339
TI  - Spirituality and positive psychology go hand in hand: an investigation of
      multiple empirically derived profiles and related protective benefits.
AB  - We investigate the relationship between personal spirituality and positive
      psychology traits as potentially presented in multiple profiles, rather than
      monolithically across a full sample. A sample of 3966 adolescents and emerging
      adults (aged 18-25, mean = 20.19, SD = 2.08) and 2014 older adults (aged 26-82,
      mean = 38.41, SD = 11.26) completed a survey assessing daily spiritual
      experiences (relationship with a Higher Power and sense of a sacred world),
      forgiveness, gratitude, optimism, grit, and meaning. To assess the relative
      protective benefits of potential profiles, we also assessed the level of
      depressive symptoms and frequency of substance use (tobacco, marijuana, alcohol,
      and heavy alcohol use). Latent class analysis (LCA) was used to examine common
      subgroupings of study participants across report on personal spirituality and
      positive psychology scales in each age cohort, with potential difference between
      latent classes then tested in level of depressive symptoms and degree of
      substance use. LCA determined a four-class and a three-class best-fitting models
      for the younger and older cohorts, respectively. Level of personal spirituality
      and level of positive psychology traits were found to coincide in 83 % of
      adolescents and emerging adults and in 71 % of older adults, suggesting personal
      spirituality and positive psychology traits go hand in hand. A minority subgroup
      of "virtuous humanists" showed high levels of positive psychology traits but low
      levels of personal spirituality, across both age cohorts. Whereas level of
      depression was found to be inversely associated with positive psychology traits
      and personal spirituality, uniquely personal spirituality was protective against
      degree of substance use across both age cohorts. Overall interpretation of the
      study findings suggests that personal spirituality may be foundational to
      positive psychology traits in the majority of people. 

PMID- 25862340
TI  - Support for adolescent spirituality: contributions of religious practice and
      trait mindfulness.
AB  - Spirituality and the surge of its development in adolescence have been
      established in the research. To date, however, these studies look at tendencies
      across full samples of adolescence rather than investigating multiple subgroups
      or multiple pathways of spiritual development. The current study uses latent
      class analysis to identify subgroup portraits of spiritual life in adolescence,
      based upon a range of dimensions of spiritual experience, religious practice, and
      mindfulness. Mindfulness, as a dispositional trait, is examined alongside the
      impact of religious practice on the level of spiritual experience (relationship
      with the Higher Power, spiritual values, and spiritual self). The findings
      suggest there is a complimentary contribution to spiritual life in adolescence
      from religious practice and mindfulness, with both as supportive pathways for
      spiritual development. Adolescents with the highest level of spiritual experience
      benefit from both religious practice and trait mindfulness, suggesting that taken
      together, there is an additive and augmenting contribution. 

PMID- 25862341
TI  - Filling the void: spiritual development among adolescents of the affluent.
AB  - Building on both the spiritual development and affluent youth literature, the
      current study explores spiritual development and health outcomes in a sample of
      upper-middle-class youth. Exploratory analyses indicate long-term stability in
      religiosity and spirituality from late adolescence (mean age 18) well into
      emerging adulthood (mean age 24); specifically, a strong personal relationship
      with a Higher Power, that carries into the broader arena of life, appears to be
      the primary source of spiritual life in adolescence that transitions into young
      adulthood. Moreover, cross-sectional associations at age 24 suggest spiritual
      development may have important implications for increased mental health and life
      satisfaction, as well as decreased antisocial behaviors. 

PMID- 25862342
TI  - The impact of the core transformation process on spirituality, symptom
      experience, and psychological maturity in a mixed age sample in India: a pilot
      study.
AB  - Research indicates that spiritual and religious constructs have the potential to
      influence a broad range of outcomes such as health, well-being, and meaning, both
      positively and negatively. This study looked at the effect of an under studied
      psycho-spiritual approach, Core Transformation (CT), in reducing symptoms and
      promoting well-being. This study also examined whether the impact of CT would be
      moderated by age, with older participants evidencing better outcomes.
      Participants from an Indian convenience sample (N = 189) ranging in age from 18
      to 65 (M = 34) received group training in CT and completed a battery of measures
      pretest and 4 weeks post-training, which included personality, spirituality, and
      psychosocial outcomes scales. Repeated-measures MANOVAs indicated significant
      improvements over time for both spirituality and symptom experience. Partial
      correlation analyses, controlling for the predictive effects of personality,
      reaffirmed the incremental validity of Spiritual Transcendence and religious
      variables in predicting symptom change and outcome ratings. CT did not appear to
      effect participants levels of psychological maturity. Age was not found to
      mediate any of these relationships, indicating the age universality of CT's
      therapeutic effects. 

PMID- 25862343
TI  - Metopic synostosis: Measuring intracranial volume change following fronto-orbital
      advancement using three-dimensional photogrammetry.
AB  - There is still disagreement regarding the intracranial volumes of patients with
      metopic synostosis compared with healthy patients. This study aimed to compare
      the intracranial volume of children with metopic synostosis before and after
      surgery to an age- and sex-matched control cohort using three-dimensional (3D)
      photogrammetry. Eighteen boys with metopic synostosis were operated on using
      standardized fronto-orbital advancement. Frontal, posterior and total
      intracranial volumes were measured exactly 1 day pre-operatively and 10 days post
      operatively, using 3D photogrammetry. To establish an age- and sex-matched
      control group, the 3D photogrammetric data of 634 healthy boys between the ages
      of 3 and 13 months were analyzed. Mean age at surgery was 9 months (SD 1.7).
      Prior to surgery, boys with metopic synostosis showed significantly reduced
      frontal and total intracranial volumes compared with the reference group, but
      similar posterior volumes. After surgery, frontal and total intracranial volumes
      did not differ statistically from the control group. As children with metopic
      synostosis showed significantly smaller frontal and total intracranial volumes
      compared with an age- and sex-matched control group, corrective surgery should
      aim to achieve volume expansion. Furthermore, 3D photogrammetry provides a
      valuable alternative to CT scans in the measurement of intracranial volume in
      children with metopic synostosis, which significantly reduces the amount of
      radiation exposure to the growing brain. 

PMID- 25862344
TI  - Lateral or oblique facial clefts associated with accessory maxillae: Review of
      the literature and report of a case.
AB  - INTRODUCTION: Lateral or oblique facial clefts associated with accessory alveolar
      processes are very rare congenital anomalies; only a few clinical cases have been
      reported in published literature. CASE REPORT AND LITERATURE REVIEW: Here, we
      present a retrospective review of 22 cases of lateral facial clefts and six cases
      of oblique facial clefts associated with accessory alveolar processes, and a case
      report of 23-year-old woman from China with bilateral transverse facial clefts
      and accessory alveolar processes. We present a summary of their clinical
      features, along with bone and teeth abnormalities. DISCUSSION: We identified 24
      cases from published English literature and four cases from Chinese literature.
      Accessory alveolar processes in lateral or oblique facial clefts occurred most
      frequently in the molar region, with pterygoid processes and maxillary
      tuberosities as the most common site. The maxilla displayed a full complement of
      deciduous and permanent teeth appropriate to his age. Supernumerary teeth
      resembled deciduous and permanent molars developed in accessory alveolar
      processes. There was no cleft in the posterior maxillary alveolus. Some were
      cases of orbital and mandibular deformation. CONCLUSION: The maxillary prominence
      was the main area of the lesion. Accessory alveolar processes may be an isolated
      pathology in lateral or oblique facial cleft.

PMID- 25862345
TI  - Genetic association between FXIII and beta-fibrinogen genes and women with
      recurrent spontaneous abortion: a meta- analysis.
AB  - BACKGROUND: FXIII Val34Leu (rs5985) and beta-fibrinogen -455G/A (rs1800790)
      genotypes have been reported to be associated with recurrent spontaneous abortion
      (RSA). However, this topic is controversial. This study aimed to explore whether
      FXIII Val34Leu or beta-fibrinogen -455G/A gene polymorphisms are related to RSA.
      METHODS: In this analysis, PubMed, HuGENet and Chinese National Knowledge
      Infrastructure (CNKI) databases were reviewed. Four models including the dominant
      model (Val/Val+Val/Leu vs. Leu/Leu), recessive model (Val/Val vs Val/Leu +
      Leu/Leu), co-dominant model (Val/Val vs. Val/Leu, Val/Val vs. Leu/Leu) and per
      allele analysis (Val vs. Leu) were applied. The odds ratio (OR) with 95%
      confidence interval (CI) was used to assess the association between RSA and FXIII
      Val34Leu and beta-fibrinogen -455G/A polymorphisms. RESULTS: Nine studies with 10
      sets of data were included according to the inclusion criterion. A positive
      association was detected in the pooled results for the dominant model
      (Val/Val+Val/Leu vs. Leu/Leu; OR = 0.417, 95% CI: 0.180-0.965, I(2) = 45.60%) and
      co-dominant model (Val/Val vs. Val/Leu; OR = 0.638, 95% CI: 0.452-0.899, I(2) =
      36.40%) for FXIII Val34Leu polymorphisms. However, no statistically significant
      association between beta-fibrinogen -455G/A polymorphisms and RSA was detected in
      the four different models, including the Asian and Caucasian subgroup analyses.
      CONCLUSIONS: Our meta-analysis demonstrates that the FXIII Val34Leu polymorphism
      has a close association with RSA and women who carry the Val allele for the FXIII
      Val34Leu polymorphism could have a protective effect against RSA. However, no
      association is detected between beta-fibrinogen -455G/A polymorphisms and the
      risk of RSA. Future well-designed studies are needed to confirm these results.

PMID- 25862346
TI  - Difficult choices for young patients with cancer: the supportive role of
      decisional counseling.
AB  - PURPOSE: The aim of patient decisional support interventions is to promote shared
      decision making. Many of these interventions are comprehensive of information and
      guidance. In this pilot study, we evaluate the effects of a decision-making
      support (decision counseling (DeCo)) on decision making, decisional conflict, and
      anxiety in cancer patients facing with values-based decisions on fertility and
      procreation or genetic testing and risk reduction options in oncology. METHODS:
      DeCo was proposed during the medical consultation. The following questionnaires
      were administered to 54 patients before the DeCo session and 1 week after it:
      stage of decision making (SDM), decisional conflict scale (DCS) and subscales
      ("uncertainty," "informed," "clarity," "support," and "effective decision"),
      state-trait anxiety inventory. Decision Support Questionnaire and Usefulness of
      Decision Counseling were created ad hoc for this study. Multivariate logistic
      models and ANCOVA models were used to investigate the changes of SDM and DCS in
      association with DeCo. RESULTS: We found a significant improving in SDM with DeCo
      (P = 0.01) and a significant reduction in DCS with DeCo (P = 0.007) measured with
      the Decision Support Questionnaire. In particular, the DCS informed subscale
      showed a significant decrease in time (P = 0.002). CONCLUSION: DeCo is useful to
      facilitate decision making and reduce decisional conflict. It plays a role in the
      perception of being informed while not directly providing clinical information.
      This model of decisional support intervention, in which information is provided
      only by the clinician and decisional support is focused on personal aspects that
      influence the decision, could improve shared decision making between patient and
      clinicians.

PMID- 25862347
TI  - Osmotically driven tensile stress in collagen-based mineralized tissues.
AB  - Collagen is the most abundant protein in mammals and its primary role is to serve
      as mechanical support in many extracellular matrices such as those of bones,
      tendons, skin or blood vessels. Water is an integral part of the collagen
      structure, but its role is still poorly understood, though it is well-known that
      the mechanical properties of collagen depend on hydration. Recently, it was shown
      that the conformation of the collagen triple helix changes upon water removal,
      leading to a contraction of the molecule with considerable forces. Here we
      investigate the influence of mineralization on this effect by studying bone and
      turkey leg tendon (TLT) as model systems. Indeed, TLT partially mineralizes so
      that well-aligned collagen with various mineral contents can be found in the same
      tendon. We show that water removal leads to collagen contraction in all cases
      generating tensile stresses up to 80MPa. Moreover, this contraction of collagen
      puts mineral particles under compression leading to strains of around 1%, which
      implies localized compressive loads in mineral of up to 800MPa. This suggests
      that collagen dehydration upon mineralization is at the origin of the compressive
      pre-strains commonly observed in bone mineral. 

PMID- 25862348
TI  - Allergic Reactions Associated with Intravenous Versus Intramuscular Pegaspargase:
      A Retrospective Chart Review.
AB  - BACKGROUND: Pegaspargase (PEG-ASP) is essential chemotherapy for acute
      lymphoblastic leukemia (ALL). Since changing to intravenous (IV) administration
      from intramuscular (IM), an increased number of allergic reactions have been
      anecdotally noted at our institution. This study compares the rate and severity
      of allergic reactions in children receiving IM or IV PEG-ASP. METHODS: We
      performed a retrospective chart review of patients treated with IV or IM PEG-ASP
      at The Hospital for Sick Children, Toronto, Canada, from March 1, 2010 to January
      1, 2012. The incidence and severity of allergic reactions attributed to PEG-ASP
      were documented. Patient age, sex, route of PEG-ASP administration, disease (risk
      group and lineage) and mean time interval between PEG-ASP doses were evaluated as
      possible risk factors for allergic reaction. RESULTS: A total of 109 patients
      were included. There were 14 (35 %) allergic reactions among 40 patients who
      received IV, compared with eight (12 %) of the 69 who received IM [odds ratio
      (OR) 4.11, 95 % confidence interval (CI) 1.54-10.97, p = 0.005]. In multivariable
      logistic regression adjusting for disease risk group, route (IV vs. IM) remained
      independently significant (p = 0.011). Patients with standard-risk ALL had a
      lower risk of experiencing an allergic reaction associated with PEG-ASP compared
      with patients in high-risk disease risk groups (collectively referred to as
      "other"; 11 vs. 31 %, OR 3.36, 95 % CI 1.16-9.72, p = 0.025). CONCLUSIONS: IV PEG
      ASP is associated with a significantly higher rate of allergic reactions than IM.
      The clinical preference for IV PEG-ASP may warrant re-evaluation.

PMID- 25862349
TI  - GMC is reviewing complaint that top NHS boss put patient safety at risk.

PMID- 25862350
TI  - Randomized study of orally administered fluorinated pyrimidines (capecitabine
      versus S-1) in women with metastatic or recurrent breast cancer: Japan Breast
      Cancer Research Network 05 Trial.
AB  - PURPOSE: Capecitabine and S-1 are orally administered fluorinated pyrimidines
      with high-level activity against metastatic breast cancer (MBC). This randomized,
      multicenter, phase II study compared the activities and safeties of the oral
      fluoropyrimidines, capecitabine and S-1, in breast cancer patients. METHODS:
      Patients with MBC were randomly assigned to receive capecitabine 825 g/m(2) twice
      daily on days 1-21 every 4 weeks or S-1 40-60 mg twice daily, according to body
      surface area, on days 1-28 every 6 weeks. The primary endpoint was progression
      free survival (PFS). RESULTS: A total of 142 patients were enrolled and
      randomized to either capecitabine (N = 73) or S-1 (N = 69). Median PFS
      (progression-free survival) was 1.2 years for capecitabine and 1.3 years for S-1,
      with a hazard ratio (S-1/capecitabine) of 0.85 (95 % confidence interval [CI]
      0.52-1.38) (P = 0.48 by log-rank). The confirmed objective response rates were
      24.0 % for capecitabine and 23.1 % for S-1 (P = 0.938). The most common treatment
      related adverse events were grade 1-2 in intensity. Thrombocytopenia (S-1: 9.2 %,
      capecitabine: 1.4 %; P = 0.040) and nausea (S-1: 26.2 %, capecitabine: 14.1 %; P
      = 0.079) were more frequent in the S-1 group, while hand-foot syndrome occurred
      more often in the capecitabine group (S-1: 10.8 %, capecitabine: 25.4 %; P =
      0.029). CONCLUSIONS: The results of the current study demonstrate that both S-1
      and capecitabine are effective and well-tolerated treatments in patients with
      MBC, while their adverse events were different. They are both convenient, orally
      administered drugs, making them attractive agents for use in outpatient
      treatment.

PMID- 25862351
TI  - Association of decreased mRNA expression of multidrug and toxin extrusion protein
      1 in peripheral blood cells with the development of flutamide-induced liver
      injury.
AB  - PURPOSE: The anti-prostate cancer drug flutamide occasionally causes
      hepatotoxicity, and predictive biomarkers of flutamide-induced liver injury
      (FILI) are needed to improve safety of this drug. The aim of this prospective
      study was to identify such a biomarker by analyzing peripheral blood samples from
      patients before flutamide therapy. METHODS: Blood samples were obtained from 52
      patients with prostate cancer before flutamide therapy. FILI was defined as
      treatment-related elevation of the serum concentration of aspartate or alanine
      aminotransferase to more than twice the upper limit of the reference range. The
      patients were monitored for at least 6 months regarding FILI. Microarray and
      quantitative real-time PCR analyses were conducted to compare gene expression
      profiles between the groups with and without FILI. RESULTS: Seventeen patients
      developed FILI. Microarray analysis of the training set in 15 patients detected
      11 annotated genes showing >twofold expression changes between the groups (p <
      0.005). Quantitative PCR analysis of both the training set and validation set
      confirmed that mRNA levels of multidrug and toxin extrusion protein 1 (MATE1 or
      SLC47A1, encoded by 1 of the 11 genes) were significantly lower in patients with
      FILI. A small experiment on mice (three per group) showed that Mate1 knockout
      mice had an elevated serum concentration of 4-nitro-3
      (trifluoromethyl)phenylamine, a major metabolite of flutamide, 2 h after
      administration of the drug, suggesting that Mate1 could affect the
      pharmacokinetics of flutamide. CONCLUSIONS: The MATE1 mRNA level in peripheral
      blood is a possible negative predictive biomarker of FILI.

PMID- 25862353
TI  - Purification and characterization of a novel plantaricin, KL-1Y, from
      Lactobacillus plantarum KL-1.
AB  - Three bacteriocins from Lactobacillus plantarum KL-1 were successfully purified
      using ammonium sulfate precipitation, cation-exchange chromatography and reverse
      phase HPLC. The bacteriocin peptides KL-1X, -1Y and -1Z had molecular masses of
      3053.82, 3498.16 and 3533.16 Da, respectively. All three peptides were stable at
      pH 2-12 and 25  degrees C and at high temperatures of 80 and 100  degrees C for
      30 min and 121  degrees C for 15 min. However, they differed in their
      susceptibility to proteolytic enzymes and their inhibition spectra. KL-1Y showed
      broad inhibitory activities against Gram-positive and Gram-negative bacteria,
      including Salmonella enterica serovar Enteritidis DMST 17368, Pseudomonas
      aeruginosa ATCC 15442, P. aeruginosa ATCC 9027, Escherichia coli O157:H7 and E.
      coli ATCC 8739. KL-1X and -1Z inhibited only Gram-positive bacteria. KL-1X, KL-1Y
      and KL-1Z exhibited synergistic activity. The successful amino acid sequencing of
      KL-1Y had a hydrophobicity of approximately 30 % and no cysteine residues
      suggested its novelty, and it was designated "plantaricin KL-1Y". Plantaricin KL
      1Y exhibited bactericidal activity against Bacillus cereus JCM 2152(T). Compared
      to nisin, KL-1Y displayed broad inhibitory activities of 200, 800, 1600, 800, 400
      and 400 AU/mL against the growth of Bacillus coagulans JCM 2257(T), B. cereus JCM
      2152(T), Listeria innocua ATCC 33090(T), Staphylococcus aureus TISTR 118, E. coli
      O157:H7 and E. coli ATCC 8739, respectively, whereas nisin had similar activities
      against only B. coagulans JCM 2257(T) and B. cereus JCM 2152(T). Therefore, the
      novel plantaricin KL-1Y is a promising antimicrobial substance for food safety
      uses in the future.

PMID- 25862354
TI  - Diversity and space-time dynamics of endophytic archaea from sugar beet in the
      north slope of Tianshan Mountain revealed by 454 pyrosequencing and T-RFLP.
AB  - Plants harbor complex and variable microbial communities. Using molecular-based
      techniques targeting the 16S rRNA gene, we studied the developmental stages and
      geographical location diversity of endophytic archaea in two locations (Shihezi
      and Changji) and four periods (the seedling growth, rosette formation, tuber
      growth and sucrose accumulation sampling periods) in the north slope of Tianshan
      Mountain, China. Community structure of mixed sample from 60 sugar beet plants
      was examined using PCR-based 454 pyrosequencing and terminal restriction fragment
      length polymorphism (T-RFLP). In total, 5290 archaea 16S rRNA sequences were
      obtained from all sugar beet samples. The most abundant archaea groups in all
      sugar beet were Methanococci, the miscellaneous Crenarchaeotic Group and
      Thermoplasmata. There was a marked difference in diversity of endophytic archaea
      in sugar beet for different growth periods. The greatest number of Operational T
      RFLP Units (OTUs) was detected during sucrose accumulation (298) and rosette
      formation (282). Endophytic archaea diversity was reduced during seedling growth
      (128 OTUs) and tuber growth (55 OTUs). Nine OTUs were common to all four periods
      of growth. There were more OTUs in Shihezi than in Changji. Clustering analysis
      and principal component analysis of T-RFLP data revealed distinct shifts in
      endophytic archaea community profiles that corresponded to plant growth stage
      rather than geographical location. The dynamics of endophytic archaea communities
      were influenced by plant growth stage. To our knowledge, this is the first report
      that archaea has been identified as endophytes associated with sugar beet by the
      culture-independent approach. The results suggest that the diversity of
      endophytic archaea is abundant in sugar beet. 

PMID- 25862355
TI  - Axial quantitative ultrasound assessment of pediatric bone quality in eastern
      Nepal.
AB  - This study presents quantitative ultrasonography (QUS) bone quality data for an
      underrepresented, south Asian pediatric population from Nepal. Data were
      collected as part of a longitudinal study of growth and development. This study
      offers normative data and documents the effect of stunting, wasting, and
      underweight on the bone properties measured by QUS. INTRODUCTION: The purpose of
      this study was to (1) examine the bone quality of a rural, non-Western pediatric
      population using QUS, (2) explore variation in the trajectory of bone quality
      development between males and females, and (3) examine the impact of growth
      disruption(s) on bone quality. METHODS: A cross-sectional study of 860 children
      and adolescents aged 5-18 years from the Jirel ethnic group in eastern Nepal was
      performed. The Sunlight Omnisense 7000P was used to assess bone quality of the
      distal 1/3 radius and midshaft tibia. WHO reference standards were used to assess
      growth disruptions of height, weight, and BMI. RESULTS: QUS bone quality data for
      an underrepresented, non-Western pediatric population are presented for the
      radius and tibia. A sizable portion of the study participants were classified as
      stunted, wasted, and/or underweight. Despite this prevalence of growth disruption
      in the study sample, bone quality data conform to other documented populations
      with less growth disruption. Thus, this study offers normative data and documents
      the minimal effect of stunting, wasting, and underweight on the bone properties
      measured by QUS. CONCLUSIONS: Non-Western pediatric populations are significantly
      underserved with regard to simple, non-invasive screening tools that may help
      identify developmental disorders and assess bone health. The children and
      adolescents examined here represent normal growth and development for an
      underrepresented south Asian population. While this work demonstrates that
      stunting, wasting, or underweight status at time of QUS assessment is not
      associated with poor bone quality, we do suggest that further study is needed to
      examine possible cumulative effects of persistent disruptions that may lead to
      compromised bone quality in later adolescence.

PMID- 25862356
TI  - Poor nutritional status is associated with a higher risk of falling and fracture
      in elderly people living at home in France: the Three-City cohort study.
AB  - Falling and fractures are a public health problem in elderly people. The aim of
      our study was to investigate whether nutritional status is associated with the
      risk of falling or fracture in community-dwelling elderly. Poor nutritional
      status was significantly associated with a higher risk of both falling and
      fractures. INTRODUCTION: Nutrition could play a role to prevent falls and
      fractures. The purpose of this study is to investigate whether a poor nutritional
      status is associated with the risk of falling and of fracture in community
      dwelling elderly. METHODS: Baseline nutritional status of participants was
      assessed using the Mini Nutritional Assessment (MNA). After a follow-up of 12
      years, 6040 individuals with available data for falls and 6839 for fracture were
      included. People who presented the outcomes at baseline were excluded. Cox models
      were used to evaluate the associations between nutritional status and the risks
      of fall or fracture. RESULTS: The frequency of poor nutritional status (MNA <=
      23.5), at baseline, was respectively 12.0% in the "fall study sample" and 12.8%
      in the "fracture study sample." Incident fall and fracture over 12 years were
      reported in 55.8 and 18.5% of the respective samples, respectively. In
      multivariate models controlled for sociodemographic data and several baseline
      health indicators, poor nutritional status was significantly associated with a
      higher risk of falling (hazard ratio (HR) = 1.66, 95% confidence interval (95%
      CI) 1.35-2.04 in men and HR = 1.20, 95% CI 1.07-1.34 in women) and with a higher
      risk of fracture (HR = 1.28, 95% CI 1.09-1.49). CONCLUSION: Poor nutritional
      status was associated with a higher risk of both falling and fractures in French
      elderly community-dwellers. Early screening and management of the nutritional
      status may be useful to reduce the frequency of these events in older people.

PMID- 25862357
TI  - Temporal profiles of high-mobility group box 1 expression levels after cortical
      spreading depression in mice.
AB  - INTRODUCTION: Cortical spreading depression (CSD) has recently been shown to
      induce the release of the nuclear protein termed high-mobility group box 1 from
      neurons, causing activation of the trigeminovascular system. Here, we explored
      the effects of single and multiple cortical spreading depression inductions on
      high-mobility group box 1 (HMGB1) transcriptional activity relative to high
      mobility group box 1 protein expression levels and intracellular localization in
      cortical neurons and astrocytes. METHODS: Single or multiple cortical spreading
      depression inductions were achieved by KCl application to the mouse cerebral
      cortex. The animals were sacrificed at 30 minutes, 3 hours and 24 hours after
      cortical spreading depression induction. High-mobility group box 1 expression
      levels were explored with in situ hybridization, Western blotting and
      immunostaining. RESULTS: Cortical spreading depression up-regulated high-mobility
      group box 1 transcriptional activity in neurons at 3 hours in a manner that was
      dependent on the number of cortical spreading depression inductions. At 24 hours,
      the high-mobility group box 1 transcriptional activity had returned to basal
      levels. Cortical spreading depression induced a reduction in high-mobility group
      box 1 protein expression at 3 hours, which was also dependent on the number of
      cortical spreading depression inductions. Following cortical spreading
      depression, the release of high-mobility group box 1 from the nucleus was
      observed in a small proportion of neurons, but not in astrocytes. CONCLUSION:
      Cortical spreading depression induced translocation of high-mobility group box 1
      from neuronal nuclei, driving transcriptional up-regulation of high-mobility
      group box 1 to maintain protein levels.

PMID- 25862352
TI  - Novel Associations between Common Breast Cancer Susceptibility Variants and Risk
      Predicting Mammographic Density Measures.
AB  - Mammographic density measures adjusted for age and body mass index (BMI) are
      heritable predictors of breast cancer risk, but few mammographic density
      associated genetic variants have been identified. Using data for 10,727 women
      from two international consortia, we estimated associations between 77 common
      breast cancer susceptibility variants and absolute dense area, percent dense area
      and absolute nondense area adjusted for study, age, and BMI using mixed linear
      modeling. We found strong support for established associations between rs10995190
      (in the region of ZNF365), rs2046210 (ESR1), and rs3817198 (LSP1) and adjusted
      absolute and percent dense areas (all P < 10(-5)). Of 41 recently discovered
      breast cancer susceptibility variants, associations were found between rs1432679
      (EBF1), rs17817449 (MIR1972-2: FTO), rs12710696 (2p24.1), and rs3757318 (ESR1)
      and adjusted absolute and percent dense areas, respectively. There were
      associations between rs6001930 (MKL1) and both adjusted absolute dense and
      nondense areas, and between rs17356907 (NTN4) and adjusted absolute nondense
      area. Trends in all but two associations were consistent with those for breast
      cancer risk. Results suggested that 18% of breast cancer susceptibility variants
      were associated with at least one mammographic density measure. Genetic variants
      at multiple loci were associated with both breast cancer risk and the
      mammographic density measures. Further understanding of the underlying mechanisms
      at these loci could help identify etiologic pathways implicated in how
      mammographic density predicts breast cancer risk.

PMID- 25862358
TI  - Skin disease in pregnancy.
AB  - Skin manifestations during pregnancy are common and diversified. This review will
      focus on the most important entities to be recognized by obstetricians. These
      are, on the one hand, physiological changes, where unnecessary investigations
      should be avoided, and on the other, the specific dermatoses of pregnancy. These
      develop electively in pregnancy, and they are currently grouped into three
      disorders: polymorphic eruption of pregnancy, atopic eczema of pregnancy, and
      pemphigoid gestationis. Arguments for recognition of these are presented
      including detection of anti-BP180 antibodies. Follow-up and treatment depend on
      the precise diagnosis. Risks in fetal prognosis may occur in rare pemphigoid
      gestationis cases. 

PMID- 25862359
TI  - Emergency Department Bouncebacks: Is Lack of Primary Care Access the Primary
      Cause?
AB  - BACKGROUND: National emergency department (ED) bounceback rates within 30 days of
      previous ED discharge have been found to be as high as 26%. We hypothesize that
      having a primary care physician (PCP) would prevent bouncebacks to the ED because
      a patient would have a medical resource for follow-up and continued care.
      METHODS: We performed a prospective, consecutive, anonymous survey study of adult
      ED patients at a suburban teaching hospital with 88,000 visits annually, from
      July 5, 2011 through August 8, 2011. Using chi-squared and Fisher's exact tests,
      we compared patients with an initial visit to those returning within 30 days of a
      previous visit to our ED. RESULTS: We collected 1084 surveys. Those in the
      bounceback group were more likely to have no insurance (10.2% vs. 4.4%) or
      Medicaid (17.7% vs. 10.8%) and less likely to have a PCP (79% vs. 86%). Of those
      with a PCP, 9% in both groups had seen their PCP that day, 58% (initial visit)
      and 49% (bouncebacks) could have been seen that day, and 35% & 36%, respectively,
      within 1 week. Of those with a PCP, 38% of initial visits and 32% of bouncebacks
      stated they had already seen their physician at least once. CONCLUSION: Our
      results suggest that patients who bounce back to the ED might have already
      contacted their PCP. Although insurance status and the lack thereof predict a
      higher likelihood to bounce back to the ED, many bouncebacks are insured patients
      with PCPs able to be seen the same day.

PMID- 25862360
TI  - Comparison of self-expanding stents with distal embolic protection to balloon
      expandable stents without a protection device in the treatment of symptomatic
      vertebral artery origin stenosis: a prospective randomized trial.
AB  - PURPOSE: To compare the angiographic and clinical outcomes of self-expanding
      stents (SES) with distal embolic protection devices (EPD) vs balloon-expandable
      stents (BES) without EPD in the treatment of symptomatic atherosclerotic
      vertebral artery ostial stenosis (VAOS). METHODS: Between July 2011 and March
      2013, a prospective randomized trial was conducted involving 127 patients (mean
      age 67.3+/-10.2 years; 94 men) with symptomatic VAOS randomly assigned to
      treatment with SES + EPD (Precise RX or RX Acculink stent + Spider FX EPD; n=61)
      or BES (Palmaz Blue or Resolute RX; n=66) without EPD. In-stent restenosis (ISR)
      >50% detected by duplex ultrasound was the primary endpoint. Technical success,
      clinical success, complications within 30 days, and signal intensity
      abnormalities on diffusion weighted imaging (DWI) after stenting were compared.
      RESULTS: The 30-day technical success rate was 95.5% (63/66) for SES+EPD vs 100%
      (70/70) for BES without EPD (p=0.072). DWI at 24 hours poststenting showed 2
      hyperintense lesions in 2 (3.3%) SES + EPD cases and 15 hyperintense lesions in
      13 (18.6%) BES patients (p<0.01). At a mean 18-month follow-up, the clinical
      success rate was 93.9% (62/66) for the SES + EPD group vs 85.7% (60/70) for the
      BES group (p=0.115). The ISR was seen in 16/70 (22.9%) arteries in the BES group
      and 2/66 (3.1%) arteries in SES + EPD group (p<0.01). Target vessel
      revascularization was performed in 7 (10.0%) BES arteries vs none in the SES +
      EPD group (p<0.01). CONCLUSION: SES with EPD in the treatment of symptomatic VAOS
      is technically feasible and safe, with low rates of ISR and significantly reduced
      thromboembolic events on imaging when compared to BES without EPD.

PMID- 25862361
TI  - Anastomotic false aneurysm of the aorta: closure with a "sandwiched" coil.
AB  - PURPOSE: To describe the treatment of a noninfected saccular anastomotic false
      aneurysm (AFA) of the abdominal aorta with the use of a single "sandwiched" coil.
      CASE REPORT: A 65-year-old man presented with a saccular AFA of the distal
      anastomosis exactly at the level of the aortic bifurcation 1 month after open
      abdominal aortic aneurysm repair. Endograft exclusion was not attempted because
      an aortouni-iliac configuration would have sacrificed a patent iliac axis. Coil
      embolization was the preferred strategy. Use of 3-dimensional rotational
      angiography and 3-dimensional roadmap was necessary to cannulate the neck of the
      AFA. Complete thrombosis and shrinkage of the sac was achieved by "sandwich
      coiling" of the neck after deployment of a single pushable hydrogel-coated coil.
      Imaging at 9 months postprocedure showed no sign of the aneurysm sac. CONCLUSION:
      This novel technique can be used for selected saccular AFAs with a narrow neck.
      In such cases, sandwich coiling may avoid sacrifice of a patent iliac axis.

PMID- 25862362
TI  - Inexplicable late type Ia endoleak associated with the low-profile Ovation
      endograft in a patient with favorable neck anatomy: treatment with transcaval
      coil embolization.
AB  - PURPOSE: To report an unusual late type Ia endoleak after endovascular aneurysm
      repair with a low-profile sealing ring endograft and its treatment with
      transcaval sac embolization. CASE REPORT: An 82-year-old man was treated for a 47
      mm abdominal aortic aneurysm associated with a 35-mm left common iliac artery
      aneurysm using an Ovation Abdominal Stent Graft System. Correct endograft
      placement was documented at 3-month follow-up. Seven months after the repair, the
      patient was admitted to the emergency department with acute left inguinal pain.
      Computed tomography showed aneurysm sac enlargement (57 mm) and a contained
      rupture of the left common iliac artery due to a late type Ia endoleak. The
      endoleak was embolized with coils and thrombin via a transcaval approach. Sac
      shrinkage without signs of endoleak was observed at 12-month follow-up.
      CONCLUSION: In this case, late endograft failure with sealing ring collapse
      created an inflow channel into the aneurysm sac, with massive type Ia endoleak.

PMID- 25862363
TI  - Intravascular ultrasound measurements after drug-eluting stent placement in
      femoropopliteal lesions: determining predictors of restenosis.
AB  - PURPOSE: To investigate the relationship between postprocedure intravascular
      ultrasound (IVUS) findings and restenosis after placement of drug-eluting stents
      (DES) for femoropopliteal lesions. METHODS: Between July 2012 and May 2013, DES
      were placed in 64 patients with 88 de novo femoropopliteal lesions. In 40
      patients (mean age 74.2+/-9.4 years; 27 men), DES were placed in 50 lesions under
      IVUS guidance, and restenosis was monitored for 1 year. All patients were
      symptomatic (Rutherford 2-6), and 17 patients (43%) suffered from critical limb
      ischemia. IVUS findings after stenting were compared for patients with vs without
      restenosis, which was defined as a peak systolic velocity ratio >2.4 on duplex
      ultrasonography or >50% diameter stenosis on angiography. RESULTS: Ten patients
      (14 lesions) developed restenosis, while 30 patients (36 lesions) did not. There
      were no significant differences in the frequency of diabetes or dialysis between
      the 2 groups. Female patients were predominant in the restenosis group (p<0.003).
      There were no significant differences of the percentage of TransAtlantic Inter
      Society Consensus C/D lesions or stent edge dissection. Multivariate analysis
      indicated that cilostazol use [odds ratio (OR) 0.13; p=0.046], distal lumen cross
      sectional area (CSA) (OR 0.86; p=0.035), and axial symmetry index (OR 0.60;
      p=0.045) were independent predictors of restenosis. Using receiver operator
      characteristic analysis, the best cutoff values of the distal lumen CSA and axial
      symmetry index for predicting restenosis were 17.1 cm(2) and 0.6, respectively.
      CONCLUSION: IVUS guidance of DES placement in femoropopliteal lesions can offer
      useful predictors of restenosis at 1 year. The utility of distal lumen CSA and
      the axial symmetry index in the prediction of restenosis after femoropopliteal
      DES placement should be confirmed in a larger cohort.

PMID- 25862364
TI  - Management of a type Ia endoleak with the Nellix endovascular aneurysm sealing
      system.
AB  - PURPOSE: To report the application of the Nellix endovascular aneurysm sealing
      (EVAS) device, including two chimney grafts, to successfully treat a type Ia
      endoleak. CASE REPORT: An 87-year-old man had an asymptomatic 7.6-cm infrarenal
      abdominal aortic aneurysm (AAA) and a 4.5-cm right internal iliac artery aneurysm
      treated using an aortouni-iliac stent-graft. Two years after the index
      endovascular repair, an asymptomatic type Ia endoleak was detected on duplex
      ultrasound; the computed tomographic angiogram (CTA) demonstrated significant sac
      enlargement and stent-graft migration. Initial attempts to treat the leak with 2
      aortic cuffs only reduced the size of the endoleak. Another procedure was
      undertaken using the Nellix device with chimney grafts to increase the proximal
      sealing zone above the existing stent-graft. Imaging postoperatively demonstrated
      successful resolution of the endoleak and continuing patency of both renal artery
      chimney stent-grafts. CTA at 6 months demonstrated persistent sealing of the
      endoleak. CONCLUSION: The use of the EVAS system may represent another
      endovascular solution that can be added to the clinician's repertoire for
      treating type Ia endoleak after conventional endovascular repair of infrarenal
      AAA.

PMID- 25862365
TI  - Stent fractures after superficial femoral artery stenting: risk factors and
      impact on patency.
AB  - PURPOSE: To determine the risk factors and clinical impact of stent fractures
      after superficial femoral artery (SFA) stenting. METHODS: From May 2009 to June
      2012, 171 consecutive patients (mean age 74.5+/-7.8, years; 106 men) who
      presented with SFA stenosis or occlusion in 205 limbs underwent stent
      implantation in the SFA at a single center. Stent fractures were determined by
      radiography and classified into types I through V. Loss of patency was assessed
      by duplex ultrasonography (>2.4 peak systolic velocity ratio) or angiography
      (percent diameter stenosis >50%). RESULTS: The 12- and 24-month primary patency
      rates were 49.8% and 43.4%, respectively. Stent fractures occurred in 12.5% and
      26.8% per limb (6.6% and 19.4% per stent) at 12 and 24 months, respectively.
      Primary patency was numerically worse in the stent fracture group but not
      statistically different from the group without fractures at 2 years. Primary
      patency for different classes of stent fracture were 30.8% (type I), 50.0% (type
      II), and 31.3% (type III-V). Hyperlipidemia (p=0.001), TransAtlantic Inter
      Society Consensus II classification (p=0.007), chronic total occlusion (CTO;
      p<0.001), proximal lesion location (p=0.008), lesion calcification (p=0.025),
      total stent length (p=0.005), stent diameter (p=0.001), and number of stents
      (p=0.001) were statistically significant predictors of stent fracture.
      Multivariate analysis showed that CTO (hazard ratio 0.173, 95% confidence
      interval 0.042 to 0.716, p=0.015) was an independent predictor of stent fracture.
      CONCLUSION: Stent fractures occur more frequently in patients with CTOs after
      treatment of longer stented lesions. Although multivariate analysis showed that
      CTO was the only independent predictor regardless of stent length or number, the
      stent fracture rate was numerically higher in the severe calcification and
      proximal SFA lesion subgroups. Stent fracture did not appear to affect long-term
      patency rates, but this is yet to be confirmed with further follow-up.

PMID- 25862366
TI  - A Systematic Review and Meta-analysis of Endovascular Popliteal Aneurysm Repair
      Using the Hemobahn/Viabahn Stent-Graft.
AB  - PURPOSE: To perform an evidence synthesis study to assess outcomes of
      endovascular repair of popliteal artery aneurysms (PAAs) using the Hemobahn or
      Viabahn stent-graft. METHODS: A systematic literature review was conducted
      conforming to established standards to identify articles published between 1996
      (the date of introduction of the Hemobahn stent-graft) and 2013 reporting stent
      graft repair of PAAs in at least 10 patients. The data were pooled for Kaplan
      Meier analysis of primary and secondary patency rates [presented with 95%
      confidence intervals (CIs)] as the primary outcomes. Random effects meta-analysis
      was performed for secondary outcomes that included rates of reintervention,
      endoleak, stent-graft fracture, and limb salvage. RESULTS: Fourteen studies
      reported outcomes for 514 PAAs. There was considerable heterogeneity in reporting
      standards among studies. Pooled primary and secondary patency rates were 69.4%
      (95% CI 63.3% to 76.2%) and 77.4% (95% CI 70.1% to 85.3%), respectively, at 5
      years. Five studies (including only one randomized controlled trial) compared
      surgical to endovascular repair; no difference was found in primary patency on
      evidence synthesis (hazard ratio 1.30, 95% CI 0.79 to 12.14, p=0.189).
      CONCLUSION: Stent-graft repair provides a feasible treatment option for
      anatomically suitable PAAs. Further studies are required to optimize both patient
      selection and follow-up protocols.

PMID- 25862367
TI  - Early experience with automatic pressure-controlled cerebrospinal fluid drainage
      during thoracic endovascular aortic repair.
AB  - PURPOSE: To report initial experience with automatic pressure-controlled
      cerebrospinal fluid drainage (CSFD) during thoracic endovascular aortic repair
      (TEVAR). METHODS: A prospective nonrandomized study enrolled 30 consecutive
      patients (median age 68 years, range 42-89; 18 men) who underwent TEVAR between
      March 2012 and July 2013 and were considered to be at high risk for postoperative
      spinal cord ischemia (SCI), fulfilling 2 of the following criteria: stent-graft
      length >20 cm, left subclavian artery coverage, and previous infrarenal aortic
      repair. All patients received perioperative CSFD via the LiquoGuard system. The
      protocol aimed for a CSF pressure of 10 mm Hg and duration of CSFD of 3 or 7 days
      in asymptomatic or symptomatic patients, respectively. Muscle strength of the
      lower extremities was assessed with the Oxford muscle strength grading scale.
      RESULTS: Completion of the CSFD protocol was achieved in 26 (87%) of 30 patients.
      CSFD was prematurely stopped due to catheter dislocation in 1 patient and bloody
      spinal fluid in 3 patients. CSFD was performed for a median of 3 days (range 1
      7). Median total CSFD volume was 714 mL (range 13-2369), with a median 192 mL
      drained per 24 hours. The SCI rate was 3% (1/30). CSFD-related complications were
      observed in 33% of the patients: 1 fatal intracranial hemorrhage, 3 bloody spinal
      fluid episodes, 3 persistent CSF leaks requiring epidural blood patch, and 3 post
      lumbar puncture headaches. Mortality during a median follow-up of 16 months
      (range 10-25) was 3% (1/30). CONCLUSION: Prophylactic CSFD was associated with a
      low SCI rate in a high-risk patient collective undergoing TEVAR. Monitoring and
      drainage by an automatic modus was feasible, reproducible, and reliable but
      associated with relevant drainage-associated complications.

PMID- 25862368
TI  - Experience of Time by People on the Go: A Theory of the Locomotion-Temporality
      Interface.
AB  - We explore the psychological interface of time and motion.Locomotion, the
      proclivity toward movement and change, constitutes a significant determinant of
      persons' orientation toward time, both as a valuable resource and as a flow
      advancing from past to future. High locomotors act quickly, multitask and refrain
      from procrastination, thus conserving time as are source Their preoccupation with
      movement, moreover, affects their relation to the flow of time High locomotors
      are future oriented and eschew preoccupation with the past. They are optimistic,
      experience little regret, generate few counterfactuals, feel little guilt about
      past wrongdoings, and leave behind past friends. Evidence accumulates that
      locomotors' "fast forward" orientation pervades diverse aspects of their behavior
      and has significant consequences for individuals and societies.

PMID- 25862370
TI  - News and controversies regarding essential tremor.
AB  - Essential tremor is the most common movement disorder in adults. It is
      characterized by a postural and kinetic tremor affecting the arms, but it can
      also affect other body parts. It evolves gradually and can be responsible for a
      functional impairment in activities of daily living. Its pathophysiology remains
      poorly understood and effective therapeutic options are limited. There are
      significant semiological variations between patients, and the term "essential
      tremor" seems to encompass a wide range of heterogeneous clinical phenotypes. The
      diagnostic criteria presented in 1998 are now challenged. Furthermore, there is a
      current debate concerning the etiology of this affection, as to whether essential
      tremor is a complex degenerative disorder or a functional reversible disorder of
      neuronal oscillation. In this review, we summarize some aspects of clinical,
      etiologic and therapeutic news, to better address the questioning on unravelling
      the clinical presentation and examine the current pathophysiological controversy
      in this disorder. 

PMID- 25862371
TI  - Myelin basic protein is a glial microtubule-associated protein --
      characterization of binding domains, kinetics of polymerization, and regulation
      by phosphorylation and a lipidic environment.
AB  - The 18.5-kDa splice isoform of myelin basic protein (MBP) predominates in the
      adult brain, adhering the cytoplasmic leaflets of the oligodendrocyte membrane
      together, but also assembling the cytoskeleton at leading edges of membrane
      processes. Here, we characterized MBP's role as a microtubule-assembly protein
      (MAP). Using light scattering and sedimentation assays we found that pseudo
      phosphorylation of Ser54 (murine 18.5-kDa sequence) significantly enhanced the
      rate but not the final degree of polymerization. This residue lies within a short
      KPGSG motif identical to one in tau, a ubiquitous MAP important in neuronal
      microtubule assembly. Using polypeptide constructs, each comprising one of three
      major amphipathic alpha-helical molecular recognition fragments of 18.5-kDa MBP,
      we identified the N-terminal alpha1-peptide as sufficient to cause microtubule
      polymerization, the rate of which was significantly enhanced in the presence of
      dodecylphosphocholine (DPC) micelles to mimic a lipidic environment. 

PMID- 25862369
TI  - New insights into the mechanism of DNA mismatch repair.
AB  - The genome of all organisms is constantly being challenged by endogenous and
      exogenous sources of DNA damage. Errors like base:base mismatches or small
      insertions and deletions, primarily introduced by DNA polymerases during DNA
      replication are repaired by an evolutionary conserved DNA mismatch repair (MMR)
      system. The MMR system, together with the DNA replication machinery, promote
      repair by an excision and resynthesis mechanism during or after DNA replication,
      increasing replication fidelity by up-to-three orders of magnitude. Consequently,
      inactivation of MMR genes results in elevated mutation rates that can lead to
      increased cancer susceptibility in humans. In this review, we summarize our
      current understanding of MMR with a focus on the different MMR protein complexes,
      their function and structure. We also discuss how recent findings have provided
      new insights in the spatio-temporal regulation and mechanism of MMR. 

PMID- 25862372
TI  - Complement activation contributes to the anti-methicillin-resistant
      Staphylococcus aureus effect of natural anti-keratin antibody.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) remains a major public health
      problem worldwide because of its strong resistance to a variety of antibiotics.
      Natural immunoglobulin (Ig) M antibodies have been reported to protect against
      microbial infections. In the present study, the function of a monoclonal natural
      anti-keratin antibody IgM (named 3B4) in MRSA infection was evaluated. The
      binding of 3B4 to MRSA was studied using immunofluorescence assay and flow
      cytometry (FCM). The binding of 3B4 to mannose-binding lectin (MBL) and
      complement activation were detected by ELISA. For the in vivo study, transgenic
      mice for the VH gene from 3B4 (TgVH 3B4) were used. After infection, the
      bacterial burden was examined in the kidney, spleen and enterocelia. Inflammatory
      cytokine levels and the neutrophil ratio in peritoneal lavage fluid (PLF) were
      assessed by ELISA and FCM, respectively. Additionally, the total serum hemolytic
      activity (CH50) in the early stage of infection was detected by ELISA. The
      results showed that 3B4 bound directly to MRSA and MBL, and the interaction
      between 3B4 and MRSA/MBL led to the activation of the classic and the MBL pathway
      in vitro. After 48 h of MRSA infection, the bacterial load in the kidney, spleen
      and enterocelia was significantly decreased in TgVH 3B4 mice (P < 0.05) compared
      with wild-type mice. Levels of IL-6, TNF-alpha, and IFN-gamma were increased
      after MRSA infection. The levels of IL-6 and TNF-alpha in TgVH 3B4 mice were
      decreased by 49.1% and 59.4% compared to wild-type mice. Additionally, the
      neutrophil ratio in the PLF of TgVH 3B4 mice was decreased by 65.9%. The CH50
      value was significantly higher in TgVH 3B4 mice than in wild-type mice,
      indicating that 3B4 promoted the activation of the complement system in MRSA
      infected mice. The results reveal an important role of 3B4 in the anti-MRSA
      immune response, and the complement activation contributes to this effect. 

PMID- 25862373
TI  - Metformin inhibits the proliferation of human prostate cancer PC-3 cells via the
      downregulation of insulin-like growth factor 1 receptor.
AB  - Metformin is a biguanide drug that is widely used for the treatment of type 2
      diabetes. Recent studies have shown that metformin inhibits cancer cell
      proliferation and tumor growth both in vitro and in vivo. The anti-tumor
      mechanisms of metformin include activation of the AMP-activated protein
      kinase/mTOR pathway and direct inhibition of insulin/insulin-like growth factor
      (IGF)-mediated cellular proliferation. However, the anti-tumor mechanism in
      prostate cancer remains unclear. Because activation of the IGF-1 receptor (IGF
      1R) is required for prostate cell proliferation, IGF-1R inhibitors may be of
      therapeutic value. Accordingly, we examined the effects of metformin on IGF-1R
      signaling in prostate cancer cells. Metformin significantly inhibited PC-3 cell
      proliferation, migration, and invasion. IGF-1R mRNA expression decreased
      significantly after 48 h of treatment, and IGF-1R protein expression decreased in
      a similar manner. IGF-1R knockdown by siRNA transfection led to inhibited
      proliferation, migration and invasion of PC-3 cells. IGF-1 activated both ERK1/2
      and Akt, but these effects were attenuated by metformin treatment. In addition,
      intraperitoneal treatment with metformin significantly reduced tumor growth and
      IGF-1R mRNA expression in PC-3 xenografts. Our results suggest that metformin is
      a potent inhibitor of the IGF-1/IGF-1R system and may be beneficial in prostate
      cancer treatment. 

PMID- 25862374
TI  - Identification and characterization of three novel hemocyte-specific promoters in
      silkworm Bombyx mori.
AB  - Insect hemocytes play essential roles in the metabolism, metamorphosis and
      immunity, which are closely related events of growth and development. Here, four
      novel hemocyte-specific genes were obtained and conformed in our study, namely,
      Bmintbeta2, Bmintbeta3, BmCatO, and BmSw04862, respectively. Subsequently, their
      promoter sequences were cloned, and their activity in hemocytes, fat body, and
      silk gland were analyzed using recombinant AcNPV vector system in vivo. Our
      results showed that Bmintbeta2, Bmintbeta3, and BmCatO were hemocyte-specific
      promoters in the silkworm, Bombyx mori. Interestingly, Bmintbeta2, and Bmintbeta3
      promoter regions were both located in their first intron. Further analysis of a
      series of BmCatO promoter truncations showed that a 254 bp region could function
      as a promoter element in the tissue-specificity expression. In summary, the
      results of this study revealed that we have identified three hemocyte-specific
      promoters in silkworm that will not only great significance for better
      understanding of hemocyte-specific gene, but also has potential applications in
      insect hematopoiesis and innate immunity research. 

PMID- 25862376
TI  - Four FCRL3 Gene Polymorphisms (FCRL3_3, _5, _6, _8) Confer Susceptibility to
      Multiple Sclerosis: Results from a Case-Control Study.
AB  - Multiple sclerosis (MS) is an autoimmune/inflammatory neurodegenerative disease
      which mainly affects the central nervous system in young adults. Fc-receptor-like
      3 (FCRL3) gene, which involved in immune cell regulation, has drawn lots of
      attentions. This study aims to investigate the association between common
      polymorphisms of FCRL3 gene and MS risk in a Chinese Han population. Nine single
      nucleotide polymorphisms (SNPs) were genotyped in 120 patients and 240 healthy
      controls through PCR assay. t test and chi-square test was conducted to find a
      possible association between FCRL3 genetic mutations and risk of MS. This
      analysis results performed that four SNPs, rs7528684 (FCRL3_3), rs945635
      (FCRL3_5), rs3761959 (FCRL3_6), and rs2282284 (FCRL3_8), were significantly
      associated with the risk of MS. Further haplotype analysis showed two haplotypes
      of FCRL3_3, 5, 6, 8, CCAG and CGAG, presented the significant associations with
      the susceptibility to MS. Four SNPs in FCRL3 gene could possibly associate with
      the susceptibility of MS in a Chinese Han population. Moreover, the haplotype
      analysis confirmed that the linkage disequilibrium exists in polymorphisms in
      FCRL3. Based on the supporting evidence, we deduced that FCRL3_3C, FCRL3_5C,
      FCRL3_6A, and FCRL3_8G caused increased risk of MS. Nevertheless, large cohort
      studies are required in the future to validate the autoimmune function. 

PMID- 25862377
TI  - Evolutionary history of fumitories (subfamily Fumarioideae, Papaveraceae): An old
      story shaped by the main geological and climatic events in the Northern
      Hemisphere.
AB  - Fumitories (subfamily Fumarioideae, Papaveraceae) represent, by their wide mainly
      northern temperate distribution (also present in South Africa) a suitable plant
      group to use as a model system for studying biogeographical links between
      floristic regions of the Northern Hemisphere and also the Southern Hemisphere
      Cape region. However, the phylogeny of the entire Fumarioideae subfamily is not
      totally known. In this work, we infer a molecular phylogeny of Fumarioideae,
      which we use to interpret the biogeographical patterns in the subfamily and to
      establish biogeographical links between floristic regions, such as those
      suggested by its different inter- and intra-continental disjunctions. The tribe
      Hypecoeae is the sister group of tribe Fumarieae, this latter holding a basal
      grade of monotypic or few-species genera with bisymmetric flowers, and a core
      group, Core Fumarieae, of more specious rich genera with zygomorphic flowers. The
      biogeographical analysis shows a subfamily that originated in East Asia at the
      end of the Early Cretaceous. From here, ancestral range expansions followed three
      different directions, one at the beginning of the Late Cretaceous by the ancestor
      of tribe Hypecoeae towards central Asia, and two during the Cretaceous-Palaeogene
      transition towards western North America and Indochina by the ancestor of the
      tribe Fumarieae. The ancestor of Core Fumarieae expanded its range from East Asia
      into the Himalayas before to the middle Eocene. The uplifts of the Qinghai
      Tibetan Plateau together with the zonal climate pattern of the Palaeogene are
      suggested to be responsible both for the accelerated diversification rate
      resulting in the origin of the basal lineages of Core Fumarieae as well as for
      the westward migration of the ancestor of Fumarieae s.str. into the Irano
      Turanian region. From here, this latter group reached South Africa during late
      Eocene and Mediterranean basin during Oligocene. There were two colonization
      waves of the Mediterranean following two different routes: a northern route
      during the early Oligocene by the subtribe Sarcocapninae, probably facilitated by
      the land bridge resulting of the Mediterranean microplate accretion; and a
      southern route into North Africa, through the Gomphotherium land bridge, taken by
      the subtribe Fumariinae between late Oligocene and middle Miocene. 

PMID- 25862375
TI  - Interplay Between Exosomes, microRNAs and Toll-Like Receptors in Brain Disorders.
AB  - Extracellular vesicles (EVs), including exosomes, microvesicles and apoptotic
      bodies, participate in intercellular communication, and particularly, in
      paracrine and endocrine signalling. The EVs and their specific contents have been
      considered hallmarks of different diseases. It has been recently discovered that
      EVs can co-transport nucleic acids such as DNAs, ribosomal RNAs, circular RNAs
      (circRNAs), long noncoding RNAs (lnRNAs) and microRNAs (miRNAs). miRNAs are
      important regulators of gene expression at the post-transcriptional level,
      although they may also play other roles. Recent evidence supports the hypothesis
      that miRNAs can activate Toll-like receptors (TLRs) under certain circumstances.
      TLRs belong to a multigene family of immune system receptors and have been
      recently described in the nervous system. In the immune system, TLRs are
      important for the recognition of the invading microorganisms, whereas in the
      nervous system, they recognise endogenous ligands released by undifferentiated or
      necrotic/injured cells. In the neuronal disease field, TLRs activity has been
      associated with amyotrophic lateral sclerosis (ALS), stroke, Alzheimer's and
      Parkinson's disease. Herein, we reviewed the current knowledge of the
      relationship between miRNA release by EVs and the inflammation signalling
      triggered by TLRs in neighbouring cells or during long-distance cell-to-cell
      communication. We highlight novel aspects of this communication mechanism,
      offering a valuable insight into such pathways in health and disease. 

PMID- 25862379
TI  - DAT1 methylation changes in alcohol-dependent individuals vs. controls.
AB  - INTRODUCTION: The dopaminergic system plays a crucial role in the development of
      alcohol dependence. Regulation of the extracellular dopamine concentration is
      driven by dopamine transporter. Both, the expression and function of dopamine
      transporter, are influenced by chronic alcohol intake. Dopamine transporter (DAT)
      gene is also supposed to be differentially methylated in alcohol-dependent
      patients than in controls. MATERIAL AND METHODS: DNA was extracted from
      peripheral blood leukocytes. We analyzed the methylation status in 23 CpG islands
      of DAT gene promoter in alcohol dependent subjects (n = 171) and control (n =
      160) group. RESULTS: No statistical differences in the general frequency of DAT
      CpG islands was revealed between patients (altogether 175 methylated islands) and
      control subjects (170 methylated islands (p = 0.86). However it was revealed that
      one of analyzed positions is significantly more often methylated in control
      subjects than in alcohol dependent individuals (p = 0.0296). CONCLUSION: Further
      subsequent studies are necessary to determine whether the methylation change of
      one (out of 23) CpG site results in DAT expression changes.

PMID- 25862378
TI  - Influence of light exposure during early life on the age of onset of bipolar
      disorder.
AB  - BACKGROUND: Environmental conditions early in life may imprint the circadian
      system and influence response to environmental signals later in life. We
      previously determined that a large springtime increase in solar insolation at the
      onset location was associated with a younger age of onset of bipolar disorder,
      especially with a family history of mood disorders. This study investigated
      whether the hours of daylight at the birth location affected this association.
      METHODS: Data collected previously at 36 collection sites from 23 countries were
      available for 3896 patients with bipolar I disorder, born between latitudes of
      1.4 N and 70.7 N, and 1.2 S and 41.3 S. Hours of daylight variables for the birth
      location were added to a base model to assess the relation between the age of
      onset and solar insolation. RESULTS: More hours of daylight at the birth location
      during early life was associated with an older age of onset, suggesting reduced
      vulnerability to the future circadian challenge of the springtime increase in
      solar insolation at the onset location. Addition of the minimum of the average
      monthly hours of daylight during the first 3 months of life improved the base
      model, with a significant positive relationship to age of onset. Coefficients for
      all other variables remained stable, significant and consistent with the base
      model. CONCLUSIONS: Light exposure during early life may have important
      consequences for those who are susceptible to bipolar disorder, especially at
      latitudes with little natural light in winter. This study indirectly supports the
      concept that early life exposure to light may affect the long term adaptability
      to respond to a circadian challenge later in life.

PMID- 25862380
TI  - Concordance of mother-daughter diurnal cortisol production: Understanding the
      intergenerational transmission of risk for depression.
AB  - A growing body of research is demonstrating concordance between mother and child
      diurnal cortisol production. In the context of maternal history of depression,
      intergenerational concordance of cortisol production could contribute to
      hypercortisolemia in children of depressed mothers, which has been shown to
      increase risk for MDD. The current study is the first to examine concordance in
      diurnal cortisol production between mothers with a history of depression and
      their never-depressed, but high-risk, children. We collected salivary cortisol
      across 2 days from mothers with (remitted; RMD) and without (CTL) a history of
      recurrent episodes of depression and their never-depressed daughters. As
      expected, RMD mothers and their daughters both exhibited higher cortisol
      production than did their CTL counterparts. Moreover, both across and within
      groups, mothers' and daughters' cortisol production were directly coupled. These
      findings suggest that there is an intergenerational concordance in cortisol
      dysregulation that may contribute to hypercortisolemia in girls at familial risk
      for depression. 

PMID- 25862381
TI  - Some factors that influence semen characteristics in rabbits.
AB  - The aim of this study, based on a five-year-long experiment, was to analyse some
      of the factors that influence rabbit sperm production. A total of 174 bucks
      between 23 and 44 weeks of age from five successive groups were used for semen
      collection one day per week, two times, at a 15 min interval (ejaculates of rank
      1 and 2), over a period of 21 weeks. Immediately after collection, pH, mass
      motility, volume and concentration were measured using classical methods, and a
      set of motility parameters were recorded by a computer-assisted semen analysis
      system. Between groups, the number of motile sperm per ejaculate, considered as a
      synthetic criterion combining both qualitative and quantitative aspects of semen
      characteristics, varied from simple to double (from 150 to 326*10(6)), reflecting
      the strong influence of uncontrolled environmental factors. Adult (37-43 weeks
      old) expressed a higher number of motile sperm/ejaculate than younger bucks (300
      vs. 205*10(6)). In autumn the number of motile sperm/ejaculate was higher than in
      summer (287 vs. 188*10(6)). Sperm production was higher on average for the first
      ejaculate compared to the second one (270 vs. 167*10(6)). For several semen
      characteristics, the effect of the collector was significant but without any
      repercussion on sperm production. Bucks born to nulliparous or primiparous does
      had higher performances. This study highlights the high variability of rabbit
      semen characteristics and the multitude of factors involved, either controlled or
      uncontrolled.

PMID- 25862383
TI  - York-Mason repair of recto-urethral fistula.

PMID- 25862384
TI  - Dokdonia pacifica sp. nov., isolated from seawater.
AB  - A Gram-stain-negative, aerobic, non-flagellated, non-gliding, oxidase- and
      catalase-positive, rod-shaped, yellow-pigmented bacterium, designated strain
      SW230(T), was isolated from a surface seawater sample collected from the South
      Pacific Gyre. Phylogenetic analysis based on 16S rRNA gene sequences indicated
      that strain SW230(T) shared highest similarity with members of the genus Dokdonia
      (95.0-94.5%), exhibiting 95.0% sequence similarity to Dokdonia genika NBRC
      100811(T). Optimal growth occurred in the presence of 2-3% (w/v) NaCl, at pH 8.0
      and at 28  degrees C. The DNA G+C content of strain SW230(T) was 36 mol%. The
      major fatty acids (>10% of the total) were iso-C15:1 G, iso-C15:0, iso-C17:0 3
      OH, and C16:1 omega7c and/or C16:1omega6c. The major respiratory quinone was
      menaquinone-6. The major polar lipids were phosphatidylethanolamine, two
      unidentified aminolipids and two unidentified lipids. On the basis of data from
      the present polyphasic study, strain SW230(T) is considered to represent a novel
      species of the genus Dokdonia, for which the name Dokdonia pacifica sp. nov. is
      proposed. The type strain is SW230(T) ( = CGMCC 1.12184(T) = JCM 18216(T)).

PMID- 25862382
TI  - Germline and somatic imprinting in the nonhuman primate highlights species
      differences in oocyte methylation.
AB  - Genomic imprinting is an epigenetic mechanism resulting in parental allele
      specific gene expression. Defects in normal imprinting are found in cancer,
      assisted reproductive technologies, and several human syndromes. In mouse models,
      germline-derived DNA methylation is shown to regulate imprinting. Though
      imprinting is largely conserved between mammals, species- and tissue-specific
      domains of imprinted expression exist. Using the cynomolgus macaque (Macaca
      fascicularis) to assess primate-specific imprinting, we present a comprehensive
      view of tissue-specific imprinted expression and DNA methylation at established
      imprinted gene clusters. For example, like mouse and unlike human, macaque IGF2R
      is consistently imprinted, and the PLAGL1, INPP5F transcript variant 2, and PEG3
      imprinting control regions are not methylated in the macaque germline but acquire
      this post-fertilization. Methylome data from human early embryos appear to
      support this finding. These suggest fundamental differences in imprinting control
      mechanisms between primate species and rodents at some imprinted domains, with
      implications for our understanding of the epigenetic programming process in
      humans and its influence on disease.

PMID- 25862385
TI  - Isolation of Jeotgalibacillus malaysiensis sp. nov. from a sandy beach, and
      emended description of the genus Jeotgalibacillus.
AB  - A Gram-stain-positive, endospore-forming, rod-shaped bacterial strain, designated
      D5(T), was isolated from seawater collected from a sandy beach in a southern
      state of Malaysia and subjected to a polyphasic taxonomic study. Sequence
      analysis of the 16S rRNA gene demonstrated that this isolate belongs to the genus
      Jeotgalibacillus, with 99.87% similarity to Jeotgalibacillus alimentarius JCM
      10872(T). DNA-DNA hybridization of strain D5(T) with J. alimentarius JCM 10872(T)
      demonstrated 26.3% relatedness. The peptidoglycan type was A1alpha linked
      directly to L-lysine as the diamino acid. The predominant quinones identified in
      strain D5(T) were menaquinones MK-7 and MK-8.The major fatty acids were iso-C15:0
      and anteiso-C15:0. The G+C content of its DNA was 43.0 mol%. The major polar
      lipids were diphosphatidylglycerol, phosphatidylglycerol and sulfoquinovosyl
      diacylglycerol, as well as two unknown phospholipids and three unknown lipids.
      The phenotypic, chemotaxonomic and genotypic data indicated that strain D5(T)
      represents a novel species of the genus Jeotgalibacillus, for which the name
      Jeotgalibacillus malaysiensis sp. nov. is proposed (type strain D5(T) = DSM
      28777(T) = KCTC33550(T)). An emended description of the genus Jeotgalibacillus is
      also provided.

PMID- 25862386
TI  - Pontibacter chinhatensis sp. nov., isolated from pond sediment containing
      discarded hexachlorocyclohexane isomer waste.
AB  - A halotolerant, Gram-negative, rod-shaped and light-red-pigmented bacterium,
      designated LP51(T), was isolated from pond sediment near a hexachlorocyclohexane
      dumpsite located at Chinhat, Lucknow, India. Phylogenetic analysis based on 16S
      rRNA gene sequences showed that strain LP51(T) formed a distinct phyletic clade
      along with the members of the genus Pontibacter. The 16S rRNA gene sequence
      similarity to members of the genus Pontibacter ranged from 94.2 to 99.4%. The
      cells were motile, aerobic and catalase- and oxidase-positive. The major fatty
      acids were iso-C15 : 0 (17.8%), iso-C15 : 0 3-OH (8.8%), iso-C17 : 0 3-OH (5.7%),
      summed feature 3 (C16 : 1omega7c and/or C16 : 1omega6c; 6.5%) and summed feature
      4 (iso-C17 : 1 I and/or anteiso-C17  : 1 B; 30.7%). The polar lipid profile of
      strain LP51(T) showed the presence of phosphatidylethanolamine, an unidentified
      aminophospholipid, unknown aminolipids, unknown polar lipids and unknown
      glycolipids. DNA-DNA relatedness of strain LP51(T) with respect to the most
      closely related type strain, Pontibacter korlensis X14-1(T), was 47.2%. On the
      basis of this information, it is proposed that the isolate be assigned to a novel
      species of the genus Pontibacter, for which the name Pontibacter chinhatensis sp.
      nov. is proposed. The type strain is LP51(T) ( = CCM 8436(T) = MCC 2070(T)).

PMID- 25862387
TI  - Mesonia hippocampi sp. nov., isolated from the brood pouch of a diseased
      Barbour's Seahorse (Hippocampus barbouri).
AB  - An orange-pigmented, Gram-staining-negative, rod-shaped bacterium, designated
      96_Hippo_TS_3/13(T) was isolated from the brood pouch of a diseased seahorse male
      of the species Hippocampus barbouri from the animal facility of the University of
      Giessen, Germany. Phylogenetic analyses based on the nearly full-length 16S rRNA
      gene sequence placed strain 96_Hippo_TS_3/13(T) into the monophyletic cluster of
      the genus Mesonia within the family Flavobacteriaceae. However, the strain shared
      only 92.2-93.8% sequence similarity to type strains of species of the genus
      Mesonia, with highest sequence similarity to the type strain of Mesonia
      aquimarina. Cellular fatty acid analysis showed a Mesonia-typical fatty acid
      profile including several branched and hydroxyl fatty acids with highest amounts
      of iso-C15 : 0 (40.9%) followed by iso-C17 : 0 3-OH (14.8%). In the polyamine
      pattern, sym-homospermidine was predominant. The diagnostic diamino acid of the
      peptidoglycan was meso-diaminopimelic acid. The quinone system contained
      exclusively menaquinone MK-6. The only identified compound in the polar lipid
      profile was phosphatidylethanolamine present in major amounts. Additionally,
      major amounts of an unidentified aminolipid and two unidentified lipids not
      containing a phosphate group, an amino group or a sugar residue were detected.
      The genomic G+C content of strain 96_Hippo_TS_3/13(T) was 30 mol%. Based on
      genotypic, chemotaxonomic and physiological characterizations we propose a novel
      species of the genus Mesonia, Mesonia hippocampi sp. nov., with strain
      96_Hippo_TS_3/13(T) ( = CIP 110839T =  LMG 28572(T) = CCM 8557(T)) as the type
      strain. An emended description of the genus Mesonia is also provided.

PMID- 25862389
TI  - Diet and Pre-eclampsia: A Prospective Multicentre Case-Control Study in Ethiopia.
AB  - INTRODUCTION: Pre-eclampsia is one of the most commonly encountered hypertensive
      disorders of pregnancy that accounts for 20-80% of maternal mortality in
      developing countries, including Ethiopia. For many years, diet has been suggested
      to play a role in pre-eclampsia. However, the hypotheses have been diverse with
      inconsistent results across studies, and this has not been studied in Ethiopia.
      OBJECTIVES: The objective of this study was to determine the effect of dietary
      habits on the incidence of pre-eclampsia in Bahir Dar, Ethiopia METHODS: A
      prospective multicentre unmatched case-control study was conducted among 453 (151
      cases and 302 controls) pregnant women attending antepartum or intrapartum care
      in public health facilities of Bahir Dar City from June to September 2014. The
      interviewer conducted a face-to-face interview, measured the mid-upper arm
      circumference (MUAC) and collected the mid-pregnancy haemoglobin level from
      clinical notes using a standardized and pretested questionnaire. Epi Info 3.5.3
      was used for data entry and cleaning, while IBM SPSS Statistics 20 was used for
      data analysis. Backward stepwise unconditional logistic regression analysis was
      employed to determine the strength of association of predictive variables with
      the outcome variable and to control for the effect of confounding variables. A P
      value <=0.05 was considered statistically significant. RESULT: For every 1-cm
      increase of MUAC, there was an increase in the incidence rate of pre-eclampsia by
      a factor of 1.35 (adjusted odds ratio (AOR)=1.35, 95% confidence interval (CI):
      1.21, 1.51). A higher incidence of pre-eclampsia was found in women who reported
      to have consumed coffee daily during pregnancy (AOR=1.78, 95% CI: 1.20, 3.05).
      Similarly, for women who had anaemia during the first trimester, the incidence of
      pre-eclampsia was 2.5 times higher than their counterparts (AOR=2.47, 95% CI:
      1.12, 7.61). This study also revealed consumption of fruit or vegetables at least
      three times a week during pregnancy to be protective against pre-eclampsia
      (AOR=0.51, 95% CI: 0.29, 0.91; AOR=0.46, 95% CI: 0.24, 0.90, respectively). In
      addition, compliance with folate intake during pregnancy has shown a significant
      independent effect on the prevention of pre-eclampsia in this study (AOR=0.16,
      95% CI: 0.08, 0.29). CONCLUSION AND RECOMMENDATION: Adequate vegetable and fruit
      consumption and compliance with folate intake during pregnancy are independent
      protective factors against pre-eclampsia. On the other hand, higher MUAC, anaemia
      and daily coffee intake during pregnancy are risk factors for the development of
      pre-eclampsia. Audience-specific education and promotion of the use of the
      protective factors identified in this study should be prioritized. The risk
      factors identified can be used for prediction and early diagnoses of pre
      eclampsia allowing timely interventions to be performed to minimize deaths
      associated with severe pre-eclampsia/eclampsia.

PMID- 25862390
TI  - Systemic ropivacaine toxicity from a peripheral nerve infusion in a medically
      complex patient.
AB  - This is a case of systemic ropivacaine toxicity from a sciatic nerve catheter. A
      20-year-old patient after heart transplant with poor systemic perfusion on
      hemodialysis and multiple medications experienced local anesthetic systemic
      toxicity 72 hours after placement of a peripheral nerve catheter. The case
      demonstrates the potentially significant impact of medical comorbidities on
      system absorption of local anesthetics and reinforces that existing dose
      guidelines are not evidence based, and literature to guide local anesthetic bolus
      supplementation of continuous infusions is scant. 

PMID- 25862392
TI  - Kinematic adaptations to tripedal locomotion in dogs.
AB  - Limb amputation often represents the only treatment option for canine patients
      with certain diseases or injuries of the appendicular system. Previous studies
      have investigated adaptations to tripedal locomotion in dogs but there is a lack
      of understanding of biomechanical compensatory mechanisms. This study evaluated
      the kinematic differences between quadrupedal and tripedal locomotion in nine
      healthy dogs running on a treadmill. The loss of the right pelvic limb was
      simulated using an Ehmer sling. Kinematic gait analysis included spatio-temporal
      comparisons of limb, joint and segment angles of the remaining pelvic and both
      thoracic limbs. The following key parameters were compared between quadrupedal
      and tripedal conditions: angles at touch-down and lift-off, minimum and maximum
      joint angles, plus range of motion. Significant differences in angular excursion
      were identified in several joints of each limb during both stance and swing
      phases. The most pronounced differences concerned the remaining pelvic limb,
      followed by the contralateral thoracic limb and, to a lesser degree, the
      ipsilateral thoracic limb. The thoracic limbs were, in general, more retracted,
      consistent with pelvic limb unloading and previous observations of bodyweight re
      distribution in amputees. Proximal limb segments showed more distinct changes
      than distal ones. Particularly, the persistently greater anteversion of the
      pelvis probably affects the axial system. Overall, tripedal locomotion requires
      concerted kinematic adjustments of both the appendicular and axial systems, and
      consequently preventive, therapeutic and rehabilitative care of canine amputees
      should involve the whole musculoskeletal apparatus. 

PMID- 25862391
TI  - Estrogen receptor alpha signaling promotes Sle1-induced loss of tolerance and
      immune cell activation and is responsible for sex bias in B6.Sle1 congenic mice.
AB  - Sex bias in lupus incidence is thought to be due, in part, to the ability of
      estrogens to promote loss of tolerance. Previously, we showed that estrogens
      promote lupus via estrogen receptor alpha (ERalpha). C57BL/6 (B6) mice carrying
      the Sle1 lupus susceptibility locus (B6.Sle1) display loss of tolerance and
      develop anti-nuclear antibodies and immune cell hyperactivation. The incidence of
      loss of tolerance in B6.Sle1 females is greater than in males. Here, we show that
      a deficiency of either estrogens or ERalpha attenuates loss of tolerance and
      autoantibody development in B6.Sle1 females. Furthermore, we demonstrate that
      immune cell activation in B6.Sle1 mice shows sex bias and that ERalpha deficiency
      diminishes this phenotype in B6.Sle1 females. Thus, estrogens, acting via
      ERalpha, control sex bias in the Sle1 phenotype. Furthermore, we show that
      ERalpha may impact the Sle1 phenotype by modulating the expression of Pbx1, one
      of genes that underlies the Sle1 locus. 

PMID- 25862393
TI  - Characterization of beta-adrenergic receptors in the heart chambers of adult
      turkeys.
AB  - The presence, distribution and characteristics of chamber-specific beta
      adrenergic receptors in adult turkey hearts were investigated by radioligand
      binding studies using (-)-[(125)I]-iodocyanopindolol (ICYP). The beta1-selective
      (CGP 20712A) and beta2-selective (ICI 118.551) antagonists as well as the
      nonselective beta-agonists isoproterenol, epinephrine and norepinephrine were
      used in displacement studies. In all cardiac chambers, ICI 118.551 and CGP 20712A
      displacement curves were monophasic and steep, with the affinity of CGP 20712A
      higher than that of ICI 118.551, indicating the exclusive presence of the beta1
      adrenergic receptor subtype. The agonist rank order of potency was isoproterenol
      > norepinephrine >= epinephrine, typical for the beta1-receptor subtype. In all
      chambers, the density of beta-adrenergic receptors was ~40 fmol/mg protein and
      the KD was ~30 pM. The study revealed similar beta-adrenergic receptor density
      mainly of the beta1-subtype in all cardiac chambers, indicating that this
      receptor subtype could contribute equally to regulate cardiac physiological
      function and pathophysiology. 

PMID- 25862394
TI  - Nanomedicine in veterinary oncology.
AB  - Nanomedicine is an interdisciplinary field that combines medicine, engineering,
      chemistry, biology and material sciences to improve disease management and can be
      especially valuable in oncology. Nanoparticle-based agents that possess functions
      such as tumor targeting, imaging and therapy are currently under intensive
      investigation. This review introduces the basic concept of nanomedicine and the
      classification of nanoparticles. Because of their favorable pharmacokinetics,
      tumor targeting properties, and resulting superior efficacy and toxicity
      profiles, nanoparticle-based agents can overcome several limitations associated
      with conventional diagnostic and therapeutic protocols in veterinary oncology.
      The two most important tumor targeting mechanisms (passive and active tumor
      targeting) and their dominating factors (i.e. shape, charge, size and
      nanoparticle surface display) are discussed. The review summarizes published
      clinical and preclinical studies that utilize different nanoformulations in
      veterinary oncology, as well as the application of nanoparticles for cancer
      diagnosis and imaging. The toxicology of various nanoformulations is also
      considered. Given the benefits of nanoformulations demonstrated in human
      medicine, nanoformulated drugs are likely to gain more traction in veterinary
      oncology.

PMID- 25862395
TI  - Naturally-occurring forelimb lameness in the horse results in significant
      compensatory load redistribution during trotting.
AB  - This study aimed to quantify the compensatory response to naturally-occurring
      forelimb lameness on load redistribution. Data from lameness investigations using
      an inertial sensor based system to monitor the response to forelimb diagnostic
      anaesthesia were reviewed. Horses with primary forelimb lameness were grouped for
      analysis as (1) all horses combined (n= 28), (2) forelimb-only lameness (n=
      8/28), (3) forelimb-contralateral hindlimb lameness (n= 14/28), (4) forelimb
      ipsilateral hindlimb lameness (n= 6/28). The effect of diagnostic anaesthesia on
      measures of head and pelvic movement asymmetry was determined using the Wilcoxon
      signed rank test. Spearman's correlation analysis was performed between forelimb
      and hindlimb variables. Statistical significance was set at P< 0.05. Forelimb
      diagnostic anaesthesia resulted in a decrease in pelvic movement asymmetry among
      all horses and the forelimb-only and forelimb-contralateral hindlimb lameness
      groups. Pelvic movement asymmetry associated with the contralateral hindlimb
      decreased by a median of 38% (interquartile range [IQR] 10-65%), 43% (IQR 28-60%)
      and 28% (IQR 12-67%) in all horses, forelimb-only and forelimb-contralateral
      hindlimb groups respectively (P< 0.05). Maximum pelvic height difference (PDMax)
      significantly decreased in all horses combined and the forelimb-contralateral
      hindlimb lameness group by a median of 66% (IQR 24-100%) and 78% (IQR 27-100%, P<
      0.01), respectively. Change in head movement asymmetry and vector sum was
      significantly positively correlated with PDMax in all horses combined and the
      forelimb-contralateral hindlimb group (P< 0.05). Forelimb lameness had a
      significant effect on hindlimb and pelvic movement in horses with clinical
      lameness resulting in compensatory load redistribution and decreased push-off
      from the contralateral hindlimb.

PMID- 25862396
TI  - Perspectives on the design of clinical trials for targeted therapies and
      immunotherapy in veterinary oncology.
AB  - The field of oncology research has undergone major changes in recent years.
      Progress in molecular and cellular biology has led to a greater understanding of
      the cellular pathways and mechanisms of cell proliferation and tissue invasion
      associated with cancer. New classes of cancer therapies are becoming available or
      are in development but these new agents require a paradigm shift in the design of
      oncology clinical trials. This review provides an overview of clinical trial
      designs for the development of tumour vaccines and targeted therapeutic agents.
      In addition, some of the successes, limitations and challenges of these trials
      are discussed, with a special emphasis on the difficulties and particularities
      that are encountered in veterinary medicine compared to similar work in human
      patients. 

PMID- 25862397
TI  - Vertebral and spinal dysplasia: A novel dominantly inherited congenital defect in
      Holstein cattle.
AB  - Monitoring and surveillance strategies are imperative for managing genetic
      defects in livestock populations in order to avoid detrimental effects on animal
      welfare and productivity. Recently, a number of previously unknown defects have
      been described in cattle, fostered by the huge progress in genome analysis and
      genomic selection. In response to reports about a potentially new defect in
      Holstein cattle, case-control studies were carried out to confirm a genetic
      background of the defect and to evaluate its phenotypic relevance. Eighty-five
      potentially affected offspring of a suspected carrier sire for the defect and 41
      matched control calves were subjected to clinical and epidemiological monitoring
      on 39 farms. Forty-one animals, all offspring of the suspected carrier sire,
      showed pathognomonic tail malformations providing highly significant evidence for
      a congenital inherited defect, which was subsequently termed vertebral and spinal
      dysplasia (VSD). The defect is characterised by vertebral (specifically tail)
      deformities and neurological dysfunctions with gait abnormalities of the hind
      limbs. The deformities and neurological dysfunctions varied from very mild (only
      tail deformities) to severe (paraparesis). Detailed epidemiological monitoring
      provided no indication of environmental factors affecting VSD. The malformations
      and dysfunctions associated with VSD, as well as its mode of inheritance and the
      genotyping of the suspected carrier sire, indicated that VSD is a defect
      previously not described in cattle. VSD is inherited in a dominant mode, but
      shows incomplete penetrance of the phenotype, which impedes unequivocal
      identification of VSD carriers. A direct diagnostic genetic test for VSD is
      available. 

PMID- 25862398
TI  - Rhoptry protein 47 gene sequence: A potential novel genetic marker for population
      genetic studies of Toxoplasma gondii.
AB  - Toxoplasma gondii, an obligate intracellular parasite, is able to infect many
      animal species and humans, and can cause toxoplasmosis of the host. In this
      study, we examined sequence variation in rhoptry protein 47 (ROP47) gene among T.
      gondii isolates originating from different hosts and geographical regions. The
      entire genome region of the ROP47 gene was amplified and sequenced, and
      phylogenetic relationship was reconstructed using maximum parsimony (MP), maximum
      likelihood (ML) and neighbor-joining (NJ), based on the ROP47 gene sequences. The
      results of sequence alignments showed that all ROP47 gene sequences were 396 bp
      in length. There were 19 variable nucleotide positions in the coding region,
      resulted in 16 amino acid substitutions (12.21%) among all examined T. gondii
      strains and the existence of polymorphic restriction sites for endonucleases SacI
      and AflIII, allowing the differentiation of the three major clonal lineage types
      I, II and III by PCR-RFLP. Phylogenetic analysis of ROP47 gene sequences showed
      that three major clonal lineage types I, II and III were clustered differently,
      consistent with PCR-RFLP results. These results suggest that ROP47 gene sequence
      may represent a potential novel genetic marker for population genetic studies of
      T. gondii isolates.

PMID- 25862399
TI  - Development and Evaluation of Two Canine Low-Fidelity Simulation Models.
AB  - Two self-made low-fidelity models for simulation of canine intubation and canine
      female urinary catheterization were developed and evaluated. We used a study
      design that compares acquired skills of two intervention groups and one control
      group in a practical examination. Fifty-eight second-year veterinary medicine
      students received a theoretical introduction to intubation and were randomly
      divided into three groups. Group I (high-fidelity) was then trained on a
      commercially available Intubation Training Manikin (item #2006, Veteffects),
      group II (low-fidelity) was trained on our low-fidelity model, and group III
      (text) read a text describing intubation of the dog. Forty-seven fifth-year
      veterinary medicine students followed the same procedure for training urinary
      catheterization using the commercially available Female Urinary Catheter Training
      Manikin (Paws 2 Claws), our self-made model, and text. Outcomes were assessed in
      a practical examination on a cadaver using an Objective Structured Clinical
      Examination (OSCE) checklist. Considering a value of p<=.05 significant,
      intervention groups performed significantly better than the text groups. Group I
      (high-fidelity) and group II (low-fidelity) showed no significant differences
      (p<=.684, intubation; p<=.901, urinary catheterization). We thereby conclude that
      low-fidelity models can be as effective as high-fidelity models for clinical
      skills training. 

PMID- 25862400
TI  - Canine Prostate Palpation Simulator as a Teaching Tool in Veterinary Education.
AB  - Adult dogs, especially elderly ones, are commonly affected by prostate diseases.
      Performing rectal palpation during physical examination in dogs is important in
      small animal clinical diagnosis. Prostate palpation training allows students to
      learn how to correctly introduce the finger into the rectum and identify the
      location, size, symmetry, and consistency of the prostate. Alternative methods
      are needed to teach this technique without using live dogs. Thus, our aim was to
      develop a canine prostate palpation simulator to provide students with the
      opportunity to learn the prostate palpation technique in dogs and to assess their
      opinion of this simulator as a teaching tool. The inner part of the canine
      mannequin contains a rotation system with three types of prostates that can be
      exchanged during the exam. Of the 64 participating students, 81% had never used
      alternative methods and 92.2% had never performed any prostatic palpation.
      According to the students' opinions, performing a clinical examination on a
      simulator allowed them to be prepared and familiarized with the palpation
      technique. They felt satisfied learning a practical method in a harmless way.
      Both the 3R (replacement, reduction, and refinement) and dog welfare principles
      were present in most of the students' concerns. We conclude that the simulator
      can help students to develop clinical skills for prostate palpation in dogs. 

PMID- 25862401
TI  - Development of a Cadaveric Model for Arthrocentesis.
AB  - This article reports the development of a novel cadaveric model for future use in
      teaching arthrocentesis. In the clinical setting, animal safety is essential and
      practice is thus limited. Objectives of the study were to develop and compare a
      model to an unmodified cadaver by injecting one of two types of fluids to
      increase yield. The two fluids injected, mineral oil (MO) and hypertonic saline
      (HS), were compared to determine any difference on yield. Lastly, aspiration
      immediately after (T1) or three hours after (T2) injection were compared to
      determine any effect on diagnostic yield. Joints used included the stifle, elbow,
      and carpus in eight medium dog cadavers. Arthrocentesis was performed before
      injection (control) and yield measured. Test joints were injected with MO or HS
      and yield measured after range of motion (T1) and three hours post injection to
      simulate lab preparation (T2). Both models had statistically significantly higher
      yield compared with the unmodified cadaver in all joints at T1 and T2 (p<.05)
      with the exception of HST2 carpus. T2 aspiration had a statistically significant
      lower yield when compared to T1HS carpus, T1HS elbow, and T1MO carpus. Overall,
      irrespective of fluid volume or type, percent yield was lower in T2 compared to
      T1. No statistically significant difference was seen between HS and MO in most
      joints with the exception of MOT1 stifle and HST2 elbow. Within the time frame
      assessed, both models were acceptable. However, HS arthrocentesis models proved
      appropriate for student trial due to the difficult aspirations with MO. 

PMID- 25862402
TI  - The SimSpay-Student Perceptions of a Low-Cost Build-It-Yourself Model for Novice
      Training of Surgical Skills in Canine Ovariohysterectomy.
AB  - Practical and ethical considerations have led to an increased use of artificial
      substitutes for live animals in veterinary surgical skills training. However,
      commercially produced models are expensive and homemade models often require full
      time staff to produce enough models for training large groups of students. In the
      Department of Veterinary Clinical and Animal Sciences of the University of
      Copenhagen, a low-cost build-it-yourself model, the SimSpay, was developed for
      novice training of surgical skills in canine ovariohysterectomy. The model did
      not require the use of trained technical staff or costly, hard-to-source
      supplies. The SimSpay was developed and implemented in the clinical veterinary
      curriculum in 2013. In 2014, 54 students participated in a questionnaire study to
      investigate their perception of the usefulness of the SimSpay as a learning tool.
      On a five-point Likert-type scale, students were asked to rate their perceived
      levels of competence, confidence, and anatomic knowledge before and after SimSpay
      training. Results demonstrate a strongly significant (p<.0001) increase in all
      three areas after training on the SimSpay. By increasing students' perceived
      levels of competence, confidence, and anatomic knowledge, the low-fidelity
      SimSpay is a useful, low-cost learning tool for teaching ovariohysterectomy. 

PMID- 25862403
TI  - Development and Efficacy of a Canine Pelvic Limb Model Used to Teach the Cranial
      Drawer and Tibial Compression Tests in the Stifle Joint.
AB  - Canine cranial cruciate ligament rupture (CCLR) is the most common cause of
      pelvic limb lameness in dogs. CCLR results in palpable stifle instability
      secondary to cranial translation of the tibial relative to the femur, and it can
      be diagnosed during the orthopedic exam using the cranial drawer test (CDT) and
      tibial compression test (TCT). Accurate diagnosis of CCLR depends on the efficacy
      in performing these tests. In this study, two three-dimensional canine pelvic
      limb models were developed: one simulating a normal stifle and one simulating
      CCLR. Thirty-eight veterinary student participants answered questionnaires and
      performed both the CDT and TCT on a randomly assigned model. Twenty-one
      participants also manipulated the models one week later to assess skill retention
      in the short term. Mean levels of reported confidence in diagnosing CCLR and
      finding anatomic landmarks for CDT/TCT were significantly higher following model
      manipulation. Nearly all participants reported that they desired a model for
      teaching the diagnosis of CCLR. Most participants (92.5%) felt that the tested
      model would be useful for teaching CCLR diagnosis. Accuracy in diagnosing CCLR
      with the TCT significantly improved over time. Participant response indicated
      that while the tested model was effective and desirable, an ideal model would be
      more durable and lifelike. Further studies are needed to evaluate the developed
      models' effectiveness for teaching CCLR diagnosis compared to traditional
      teaching methods. 

PMID- 25862404
TI  - Comparative Study of Three Different Personal Response Systems with Fourth-Year
      Undergraduate Veterinary Students.
AB  - The purpose of this study was to compare three different Personal Response
      Systems that have been used in recent years at the School of Veterinary Science,
      University of Liverpool: a technology-free system (Communicubes), a handset
      delivery device (TurningPoint), and a cloud-based technology (Poll Everywhere)
      that allows students to use a range of personal computing devices to register
      their answer. All three systems offer a method to promote active learning, and
      lecturers were encouraged to use them. However, there are cost and logistical
      implications for each. The authors found that both staff and students did have
      particular preferences for a specific system. This preference was not the same
      for both groups. The outcome of the comparison is that further research is needed
      into cloud-based technology as it offers benefits to the students but is also a
      distraction. 

PMID- 25862406
TI  - N-linked glycosylation of human SLC1A5 (ASCT2) transporter is critical for
      trafficking to membrane.
AB  - The human amino acid transporter SLC1A5 (ASCT2) contains two N-glycosylation
      sites (N163 and N212) located in the large extracellular loop. In the homology
      structural model of ASCT2 these Asn residues are extracellularly exposed. Mutants
      of the two Asn exhibited altered electrophoretic mobility. N163Q and N212Q
      displayed multiple bands with apparent molecular masses from 80kDa to 50kDa.
      N163/212Q displayed a single band of 50kDa corresponding to the unglycosylated
      protein. The presence in membrane of WT and mutants was evaluated by protein
      biotinylation assay followed by immunoblotting. The double mutation significantly
      impaired the presence of the protein in membrane, without impairment in protein
      synthesis. [(3)H]glutamine transport was measured in cells transiently
      transfected with the WT or mutants. N163/212Q exhibited a strongly reduced
      transport activity correlating with reduced surface expression. The same proteins
      extracted from cells and reconstituted in liposomes showed comparable transport
      activities demonstrating that the intrinsic transport function of the mutants was
      not affected. The rate of endocytosis of ASCT2 was assayed by a reversible
      biotinylation strategy. N212Q and N163/212Q showed strongly increased rates of
      endocytosis respect to WT. ASCT2 stability was determined using cycloheximide.
      N163Q or N163/212Q showed a slightly or significantly lower stability with
      respect to WT. To assess trafficking to the membrane, a brefeldin-based assay,
      which caused retention of proteins in ER, was performed. One hour after brefeldin
      removal WT protein was localized to the plasma membrane while the double mutant
      was localized in the cytosol. The results demonstrate that N-glycosylation is
      critical for trafficking. 

PMID- 25862407
TI  - Predictive factors for and incidence of hospital readmissions of patients with
      acute and chronic pancreatitis.
AB  - BACKGROUND/OBJECTIVE: Acute and chronic pancreatitis are common
      gastroenterological disorders that have a fairly unpredictable long-term course
      often associated with unplanned hospital readmissions. Little is known about the
      factors that increase or decrease the risk for a hospital readmission. The aim of
      this study was to identify positive and negative predictive factors for hospital
      readmissions of patients with acute and chronic pancreatitis after in-hospital
      treatment. METHODS: In a retrospective analysis data from the hospital
      information and reimbursement data system (HIS) were evaluated for 606 hospital
      stays for either acute or chronic pancreatitis between 2006 and 2011. Additional
      clinical data were obtained from a questionnaire covering quality of life and
      socio-economic status. A total of 973 patient variables were assessed by
      bivariate and multivariate analysis. RESULTS: Between 2006 and 2011, 373 patients
      were admitted for acute or chronic pancreatitis; 107 patients of them were
      readmitted and 266 had only one hospitalization. Predictors for readmission were
      concomitant liver disease, presence of a pseudocyst or a suspected tumor of the
      pancreas as well as alcohol, tobacco or substance abuse or coexisting mental
      disorders. Patients who had undergone a CT-scan were more susceptible to
      readmission. Lower readmissions rates were found in patients with diabetes
      mellitus or gallstone disease as co-morbidity. CONCLUSION: While factors like age
      and severity of the initial disease cannot be influenced to reduce the
      readmission rate for pancreatitis, variables like alcohol, tobacco and drug abuse
      can be addressed in outpatient programs to reduce disease recurrence and
      readmission rates for pancreatitis.

PMID- 25862408
TI  - Influence of surface treatment on the resin-bonding of zirconia.
AB  - OBJECTIVE: To compare the effect of various surface treatments on the bonding of
      luting resin cements to zirconia under four-point bending. METHODS: Bar specimens
      (n = 200) (2 mm * 5 mm * 25 mm) were prepared from zirconia blocks (VITA In-Ceram
      YZ, Vita Zahnfabrik) with the cementation surface (2 mm * 5 mm) of groups of 40
      treated in one of five ways: airborne particle abrasion with 50MUm Al2O3 (GB),
      zirconia primer (Z-Prime Plus, Bisco) (Z), glaze ceramic (Crystall.Glaze spray,
      Ivoclar Vivadent) + hydrofluoric acid (GHF), fusion glass-ceramic
      (Crystall.Connect, Ivoclar Vivadent) (CC), or left untreated as control (C).
      Within each treatment, bars were cleaned ultrasonically for 15 min in ethanol and
      then deionized water before bonding in pairs with one of two luting resins:
      Panavia F 2.0, (Kuraray) (P); RelyX U-200 (3M/Espe) (R), to form 10 test
      specimens for each treatment and lute combination. Mechanical tests were
      performed and bond strengths (MPa) were subject, after log transformation, to
      analysis of variance, Shapiro-Wilk and Holm-Sidak tests; also log-linear
      contingency analysis of failure mode distribution; all with alpha = 0.05.
      Fracture surfaces were examined under light and scanning electron microscopy.
      RESULTS: While the effect of surface treatment was significant (p = 1.27 * 10(
      9)), there was no detected effect due to resin (p = 0.829). All treatments except
      CC (30.1 MPa *// 1.44)* were significantly better than the untreated control
      (24.8 MPa *// 1.35) (p = 3.28 * 10(-9)). While the effect of GB - which gave the
      highest mean strength (50.5 MPa *// 1.29) - was not distinguishable from that of
      GHF (39.9 MPa *// 1.29) (p = 0.082), it was significantly better than treatment
      with either CC or Z (33.1 MPa *// 1.48) (p < 0.05). (* After log transformation
      for analysis and back; asymmetric error bounds as s.d. in log values.)
      SIGNIFICANCE: The novel test method design, which has good discriminatory power,
      confirmed the value of gritblasting as a simple and effective treatment with low
      operator hazard. It gave the highest bond strengths regardless of the cement
      type. Glaze layer application followed by hydrofluoric acid-etching on zirconia
      before cementation might be viable for adhesive zirconia cementation, but
      represents a much greater hazard as well as having problems with thickness
      control.

PMID- 25862405
TI  - Cell biology of yeast zygotes, from genesis to budding.
AB  - The zygote is the essential intermediate that allows interchange of nuclear,
      mitochondrial and cytosolic determinants between cells. Zygote formation in
      Saccharomyces cerevisiae is accomplished by mechanisms that are not
      characteristic of mitotic cells. These include shifting the axis of growth away
      from classical cortical landmarks, dramatically reorganizing the cell cortex,
      remodeling the cell wall in preparation for cell fusion, fusing with an adjacent
      partner, accomplishing nuclear fusion, orchestrating two steps of septin
      morphogenesis that account for a delay in fusion of mitochondria, and
      implementing new norms for bud site selection. This essay emphasizes the sequence
      of dependent relationships that account for this progression from cell encounters
      through zygote budding. It briefly summarizes classical studies of signal
      transduction and polarity specification and then focuses on downstream events. 

PMID- 25862409
TI  - Use of a facilitated discussion model for antenatal care to improve
      communication.
AB  - BACKGROUND: Achieving health literacy is a critical step to improving health
      outcomes and the health of a nation. However, there is a lack of research on
      health literacy in low-resource countries, where maternal health outcomes are at
      their worst. OBJECTIVES: To examine the usefulness and feasibility of providing
      focused antenatal care (FANC) in a group setting using picture cards to improve
      patient-provider communication, patient engagement, and improve health literacy.
      DESIGN: An exploratory, mixed methods design was employed to gather pilot data
      using the Health Literacy Skills Framework. SETTINGS: A busy urban district
      hospital in the Ashanti Region of Ghana was used to gather data during 2014.
      PARTICIPANTS: A facility-driven convenience sample of midwives (n=6) aged 18
      years or older, who could speak English or Twi, and had provided antenatal care
      at the participating hospital during the previous year prior to the start of the
      study participated in the study. METHODS: Data were collected using pre-test and
      post-test surveys, completed three months after the group FANC was implemented. A
      semi-structured focus group was conducted with four of the participating midwives
      and the registered nurse providing support and supervision for the study (n=5) at
      the time of the post-test. Data were analyzed concurrently to gain a broad
      understanding of patient communication, engagement, and group FANC. RESULTS:
      There were no significant differences in the mean communication (t(df=3)=0.541,
      p=0.626) and engagement (t(df=3)=-0.775, p=0.495) scores between the pre- and
      post-test. However, the focus group revealed the following themes: (a) improved
      communication through the use of picture cards; (b) enhanced information sharing
      and peer support through the facilitated group process and; and (c) an improved
      understanding of patient concerns. CONCLUSIONS: The improved communication noted
      through the use of picture cards and the enhanced information sharing and peer
      support elicited through the group FANC undoubtedly provided patients with
      additional tools to invoke self-determination, and carry out the behaviors they
      thought were most important to improve pregnancy outcomes.

PMID- 25862410
TI  - The cost of pressure ulcer prevention and treatment in hospitals and nursing
      homes in Flanders: A cost-of-illness study.
AB  - INTRODUCTION: The economic impact of pressure ulcer prevention and treatment is
      high. The results of cost-of-illness studies can assist the planning, allocation,
      and priority setting of healthcare expenditures to improve the implementation of
      preventive measures. Data on the cost of current practice of pressure ulcer
      prevention or treatment in Flanders, a region of Belgium, is lacking. AIM: To
      examine the cost of pressure ulcer prevention and treatment in an adult
      population in hospitals and nursing homes from the healthcare payer perspective.
      DESIGN: A cost-of-illness study was performed using a bottom-up approach.
      SETTINGS: Hospitals and nursing homes in Flanders, a region of Belgium. METHODS:
      Data were collected in a series of prospective multicentre cross-sectional
      studies between 2008 and 2013. Data collection included data on risk assessment,
      pressure ulcer prevalence, preventive measures, unit cost of materials for
      prevention and treatment, nursing time measurements for activities related to
      pressure ulcer prevention and treatment, and nursing wages. The cost of pressure
      ulcer prevention and treatment in hospitals and nursing homes was calculated as
      annual cost for Flanders, per patient, and per patient per day. RESULTS: The mean
      (SD) cost for pressure ulcer prevention was ?7.88 (8.21) per hospitalised patient
      at risk per day and ?2.15 (3.10) per nursing home resident at risk per day. The
      mean (SD) cost of pressure ulcer prevention for patients and residents identified
      as not at risk for pressure ulcer development was ?1.44 (4.26) per day in
      hospitals and ?0.50 (1.61) per day in nursing homes. The main cost driver was the
      cost of labour, responsible for 79-85% of the cost of prevention. The mean (SD)
      cost of local treatment per patient per day varied between ?2.34 (1.14) and
      ?77.36 (35.95) in hospitals, and between ?2.42 (1.15) and ?16.18 (4.93) in
      nursing homes. CONCLUSIONS: Related to methodological differences between
      studies, the cost of pressure ulcer prevention and treatment in hospitals and
      nursing homes in Flanders was found to be low compared to other international
      studies. Recommendations specific to pressure ulcer prevention are needed as part
      of methodological guidelines to conduct cost-of-illness studies.

PMID- 25862411
TI  - Observation of interprofessional collaborative practice in primary care teams: An
      integrative literature review.
AB  - BACKGROUND: Interprofessional collaboration improves patient care, especially for
      those patients with complex and/or chronic conditions. Many studies examining
      collaborative practice in primary care settings have been undertaken, yet
      identification of essential elements of effective interprofessional collaboration
      in primary care settings remains obscure. OBJECTIVE: To examine the nature of
      interprofessional collaboration (including interprofessional collaborative
      practice) and the key influences that lead to successful models of
      interprofessional practice in primary care teams, as reported in studies using
      direct observation methods. DESIGN: Integrative review using Whittemore and
      Knafl's (2005) five stage framework: problem identification, literature search,
      data evaluation, data analysis and presentation. Data sources and review method:
      Primary research studies meeting the search criteria were accessed from MEDLINE,
      PsycINFO, Scopus, King's Fund and Informit Health Collection databases, and by
      hand-searching reference lists. From 2005 to 2013, 105 studies closely examining
      elements of interprofessional collaboration were identified. Of these, 11 studies
      were identified which incorporated a range of 'real time' direct observation
      methods where the collaborative practice of health professionals was closely
      observed. RESULTS: Constant opportunity for effective, frequent, informal shared
      communication emerged as the overarching theme and most critical factor in
      achieving and sustaining effective interprofessional collaboration and
      interprofessional collaborative practice in this review. Multiple channels for
      repeated (often brief) informal shared communication were necessary for shared
      knowledge creation, development of shared goals, and shared clinical decision
      making. Favourable physical space configuration and 'having frequent brief time
      in common' were key facilitators. CONCLUSION: This review highlights the need to
      look critically at the body of research purported to investigate
      interprofessional collaboration in primary care settings and suggests the value
      of using direct observational methods to elucidate this. Direct observation of
      collaborative practice in everyday work settings holds promise as a method to
      better understand and articulate the complex phenomena of interprofessional
      collaboration, yet only a small number of studies to date have attempted to
      directly observe such practice. Despite methodological challenges, findings
      suggest that observation data may contribute in a unique way to the teamwork
      discourse, by identifying elements of interprofessional collaborative practice
      that are not so obvious to individuals when asked to self-report.

PMID- 25862413
TI  - Quantification of propionaldehyde in breath of patients after lung
      transplantation.
AB  - Oxygen-derived free radicals (ROS) have been identified to contribute
      significantly to ischemia-reperfusion (I/R) injury by initiating chain reactions
      with polyunsaturated membrane lipids (lipid peroxidation, LPO) resulting in the
      generation of several aldehydes and ketones. Due to their volatile nature these
      LPO products can be measured noninvasively in breath. We hypothesized that one of
      these markers, namely propionaldehyde, will be increased in lung and heart-lung
      transplant patients where severe oxidative stress due to I/R injury with early
      graft dysfunction represents one of the major postoperative complications
      resulting in prolonged ventilation and increased in-hospital morbidity and
      mortality. Expiratory air measurements for acetone, isoprene, and propionaldehyde
      were performed in seven patients after lung (n = 5) or heart-lung (n = 2)
      transplantation, ventilated patients (n = 12), and healthy volunteers (n = 17)
      using online ion-molecule reaction mass spectrometry. Increased concentrations of
      acetone (transplanted: 3812 [2347-12498]; ventilated: 1255 [276-1959]; healthy:
      631 [520-784] ppbv; P < .001) and propionaldehyde (transplanted: 270 [70-424];
      ventilated: 82 [41.8-142]; healthy: 1.7 [0.1-11.8] ppbv; P < .001) were found in
      expiratory air of transplanted and ventilated patients. Propionaldehyde resulting
      from spontaneous fragmentation of peroxides due to free radical-induced LPO after
      I/R injury in patients after lung or heart-lung transplantation can be quantified
      in expired breath.

PMID- 25862412
TI  - Prion protein functions as a ferrireductase partner for ZIP14 and DMT1.
AB  - Excess circulating iron is stored in the liver, and requires reduction of non-Tf
      bound iron (NTBI) and transferrin (Tf) iron at the plasma membrane and endosomes,
      respectively, by ferrireductase (FR) proteins for transport across biological
      membranes through divalent metal transporters. Here, we report that prion protein
      (PrP(C)), a ubiquitously expressed glycoprotein most abundant on neuronal cells,
      functions as a FR partner for divalent-metal transporter-1 (DMT1) and ZIP14.
      Thus, absence of PrP(C) in PrP-knock-out (PrP(-/-)) mice resulted in markedly
      reduced liver iron stores, a deficiency that was not corrected by chronic or
      acute administration of iron by the oral or intraperitoneal routes. Likewise,
      preferential radiolabeling of circulating NTBI with (59)Fe revealed significantly
      reduced uptake and storage of NTBI by the liver of PrP(-/-) mice relative to
      matched PrP(+/+) controls. However, uptake, storage, and utilization of ferritin
      bound iron that does not require reduction for uptake were increased in PrP(-/-)
      mice, indicating a compensatory response to the iron deficiency. Expression of
      exogenous PrP(C) in HepG2 cells increased uptake and storage of ferric iron
      (Fe(3+)), not ferrous iron (Fe(2+)), from the medium, supporting the function of
      PrP(C) as a plasma membrane FR. Coexpression of PrP(C) with ZIP14 and DMT1 in
      HepG2 cells increased uptake of Fe(3+) significantly, and surprisingly, increased
      the ratio of N-terminally truncated PrP(C) forms lacking the FR domain relative
      to full-length PrP(C). Together, these observations indicate that PrP(C)
      promotes, and possibly regulates, the uptake of NTBI through DMT1 and Zip14 via
      its FR activity. Implications of these observations for neuronal iron homeostasis
      under physiological and pathological conditions are discussed. 

PMID- 25862414
TI  - Evaluation of oxygen dependence on in vitro and in vivo cytotoxicity of
      photoimmunotherapy using IR-700-antibody conjugates.
AB  - Photoimmunotherapy (PIT) using the near-infrared-absorbing photosensitizing
      phthalocyanine dye, IRDye 700DX (IR-700), conjugated with a tumor-targeting
      antibody such as panitumumab (Pan) has shown efficacy in in vitro studies and
      several preclinical models in mice with promise for clinical translation. PIT
      results in rapid necrotic cell death in vitro and tumor shrinkage in vivo.
      Photochemical studies with the Pan-IR-700 conjugate showed that this agent can
      support generation of singlet oxygen and also generate reactive oxygen species
      after exposure to near-infrared (NIR) light. Moreover, in vitro studies using
      A431 cells, singlet oxygen scavengers abrogated the efficacy of PIT with Pan-IR
      700, while oxygen depletion to undetectable levels in the exposure chamber almost
      completely inhibited the cellular cytotoxicity of PIT. Survival of tumor bearing
      mice was prolonged in PIT-treated animals but mice whose tumors were made
      transiently hypoxic prior to PIT had no benefit from the treatment. The results
      from this study support a central role for molecular oxygen-derived species in
      cell death caused by PIT. 

PMID- 25862415
TI  - Allelic variations in the CYBA gene of NADPH oxidase and risk of kidney
      complications in patients with type 1 diabetes.
AB  - Oxidative stress plays a pivotal role in the pathophysiology of diabetic
      nephropathy, and the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase
      system is an important source of reactive oxygen species in hyperglycemic
      conditions in the kidney. Plasma concentration of advanced oxidation protein
      products (AOPP), a marker of oxidative stress, is increased in patients with
      diabetic nephropathy. We investigated associations of variants in the CYBA gene,
      encoding the regulatory subunit p22(phox) of NADPH oxidase, with diabetic
      nephropathy and plasma AOPP and myeloperoxidase (MPO) concentrations in type 1
      diabetic patients. Seven SNPs in the CYBA region were analyzed in 1357 Caucasian
      subjects with type 1 diabetes from the SURGENE (n=340), GENEDIAB (n=444), and
      GENESIS (n=573) cohorts. Duration of follow-up was 10, 9, and 6 years,
      respectively. Cox proportional hazards and logistic regression analyses were used
      to estimate hazard ratios (HR) or odds ratios (OR) for incidence and prevalence
      of diabetic nephropathy. The major G-allele of rs9932581 was associated with the
      incidence of renal events defined as new cases of microalbuminuria or the
      progression to a more severe stage of nephropathy during follow-up (HR 1.59, 95%
      CI 1.17-2.18, P=0.003) in SURGENE. The same allele was associated with
      established/advanced nephropathy (OR 1.52, 95% CI 1.22-1.92, P=0.0001) and with
      the incidence of end-stage renal disease (ESRD) (HR 2.01, 95% CI 1.30-3.24,
      P=0.001) in GENEDIAB/GENESIS pooled studies. The risk allele was also associated
      with higher plasma AOPP concentration in subsets of SURGENE and GENEDIAB, with
      higher plasma MPO concentration in a subset of GENEDIAB, and with lower estimated
      glomerular filtration rate (eGFR) in the three cohorts. In conclusion, a
      functional variant in the promoter of the CYBA gene was associated with lower
      eGFR and with prevalence and incidence of diabetic nephropathy and ESRD in type 1
      diabetic patients. These results are consistent with a role for NADPH oxidase in
      the pathophysiology of kidney complications of diabetes. 

PMID- 25862417
TI  - [Cleaning and disinfection of surfaces in hospitals: Data on structure, process
      and result in the Frankfurt/Main Metropolitan Area].
AB  - INTRODUCTION: In addition to hand hygiene and reprocessing of medical products,
      cleaning and disinfection of surfaces is also an important issue in the
      prevention of germ transmission and by implication infections. Therefore, in
      2014, the quality of the structure, process and result of surface preparation of
      all hospitals in Frankfurt am Main, Germany, was monitored. METHODS: All 17
      hospitals transferred information on the quality of structure. Process quality
      was obtained through direct observation during cleaning and disinfection of rooms
      and their plumbing units. Result quality was gained using the fluorescent method,
      i.e. marking surfaces with a fluorescent liquid and testing if this mark has been
      sufficiently removed by cleaning. RESULTS: Structure quality: in all hospitals
      the employees were trained regularly. In 12 of them, the foremen had the required
      qualifications, in 6 hospitals unclarity as to the intersection of the cleaning
      and care services remained. In 14 hospitals only visible contamination was
      cleaned on the weekends, whereas complete cleaning was reported to take place in
      12 hospitals on Saturdays and in 2 hospitals on Sundays. The contractually
      stipulated cleaning (observations specified in brackets) averaged 178 m(2)/h (148
      m(2)/h) per patient room and 69 m(2)/h (33 m(2)/h) for bathrooms. Process
      quality: during process monitoring, various hand contact surfaces were prepared
      insufficiently. Result quality: 63 % of fluorescent markings were appropriately
      removed. CONCLUSION: The need for improvement is given especially in the area of
      the qualification of the foremen and a in a clear definition of the intersection
      between cleaning and care services, as well as in the regulations for weekends
      and public holidays.

PMID- 25862416
TI  - Longitudinal alterations to brain function, structure, and cognitive performance
      in healthy older adults: A fMRI-DTI study.
AB  - Cross-sectional research has shown that older adults tend to have different
      frontal cortex activation patterns, poorer brain structure, and lower task
      performance than younger adults. However, relationships between longitudinal
      changes in brain function, brain structure, and cognitive performance in older
      adults are less well understood. Here we present the results of a longitudinal,
      combined fMRI-DTI study in cognitive normal (CN) older adults. A two time-point
      study was conducted in which participants completed a task switching paradigm
      while fMRI data was collected and underwent the identical scanning protocol an
      average of 3.3 years later (SD=2 months). We observed longitudinal fMRI
      activation increases in bilateral regions of lateral frontal cortex at time point
      2. These fMRI activation increases were associated with longitudinal declines in
      WM microstructure in a portion of the corpus callosum connecting the increasingly
      recruited frontal regions. In addition, the fMRI activation increase in the left
      VLPFC was associated with longitudinal increases in response latencies. Taken
      together, our results suggest that local frontal activation increases in CN older
      adults may in part reflect a response to reduced inter-hemispheric signaling
      mechanisms. 

PMID- 25862418
TI  - MBL-associated serine proteases (MASPs) and infectious diseases.
AB  - The lectin pathway of the complement system has a pivotal role in the defense
      against infectious organisms. After binding of mannan-binding lectin (MBL),
      ficolins or collectin 11 to carbohydrates or acetylated residues on pathogen
      surfaces, dimers of MBL-associated serine proteases 1 and 2 (MASP-1 and MASP-2)
      activate a proteolytic cascade, which culminates in the formation of the membrane
      attack complex and pathogen lysis. Alternative splicing of the pre-mRNA encoding
      MASP-1 results in two other products, MASP-3 and MAp44, which regulate activation
      of the cascade. A similar mechanism allows the gene encoding MASP-2 to produce
      the truncated MAp19 protein. Polymorphisms in MASP1 and MASP2 genes are
      associated with protein serum levels and functional activity. Since the first
      report of a MASP deficiency in 2003, deficiencies in lectin pathway proteins have
      been associated with recurrent infections and several polymorphisms were
      associated with the susceptibility or protection to infectious diseases. In this
      review, we summarize the findings on the role of MASP polymorphisms and serum
      levels in bacterial, viral and protozoan infectious diseases. 

PMID- 25862419
TI  - Acute amnestic encephalopathy in amyloid-beta oligomer-injected mice is due to
      their widespread diffusion in vivo.
AB  - Amyloid-beta (Abeta) oligomers are the suspected culprit as initiators of
      Alzheimer's disease (AD). However, their diffusion in the brain remains unknown.
      Here, we studied Abeta oligomers' dissemination and evaluated their in vivo
      toxicity. Wild-type mice were injected with 50 pmol of synthetic Abeta oligomers
      (of different size) in the hippocampus. Oligomers diffused largely in the brain
      as soon as 1 hour and up to 7 days after injection. A transient encephalopathy
      with memory impairment was induced by this unique injection. The immunoreactivity
      of the postsynaptic marker PSD95 was diffusely decreased. Similar results (both
      on memory and PSD95 immunoreactivity) were obtained with delipidated and high
      molecular weight oligomers (>50 kDa) but not with smaller assemblies. Tau
      hyperphosphorylation was observed in the oligomer-injected brains. Finally, fos
      immunostaining was increased in Abeta-derived diffusible ligands-injected mice,
      suggesting neuronal hyperactivity. Rapid and widespread diffusion of Abeta
      oligomers was demonstrated in vivo and associated with decreased synaptic markers
      and memory deficits which gives new insight to the pathogenicity of Abeta.

PMID- 25862420
TI  - The effect of TOMM40 on spatial navigation in amnestic mild cognitive impairment.
AB  - The very long (VL) poly-T variant at rs10524523 ("523") of the TOMM40 gene may
      hasten the onset of late-onset Alzheimer's disease (LOAD) and induce more
      profound cognitive impairment compared with the short (S) poly-T variant. We
      examined the influence of TOMM40 "523" polymorphism on spatial navigation and its
      brain structural correlates. Participants were apolipoprotein E (APOE)
      epsilon3/epsilon3 homozygotes with amnestic mild cognitive impairment (aMCI). The
      homozygotes were chosen because APOE epsilon3/epsilon3 variant is considered
      "neutral" with respect to LOAD risk. The participants were stratified according
      to poly-T length polymorphisms at "523" into homozygous for S (S/S; n = 16),
      homozygous for VL (VL/VL; n = 15) TOMM40 poly-T variant, and heterozygous (S/VL;
      n = 28) groups. Neuropsychological examination and testing in real-space human
      analog of the Morris Water Maze were administered. Both self-centered
      (egocentric) and world-centered (allocentric) spatial navigation was assessed.
      Brain magnetic resonance imaging scans were analyzed using FreeSurfer software.
      The S/S group, although similar to S/VL and VL/VL groups in demographic and
      neuropsychological profiles, performed better on allocentric navigation (p <=
      0.004) and allocentric delayed recall (p <= 0.014), but not on egocentric
      navigation. Both S/VL and VL/VL groups had thinner right entorhinal cortex (p <=
      0.043) than the S/S group, whereas only the VL/VL group had thinner left
      entorhinal cortex (p = 0.043) and left posterior cingulate cortex (p = 0.024)
      than the S/S group. In conclusion, TOMM40 "523" VL variants are related to
      impairment in allocentric spatial navigation and reduced cortical thickness of
      specific brain regions among aMCI individuals with (LOAD neutral) APOE
      epsilon3/epsilon3 genotype. This may reflect a specific role of TOMM40 "523" in
      the pathogenesis of LOAD.

PMID- 25862421
TI  - Resting-state synchrony between the retrosplenial cortex and anterior medial
      cortical structures relates to memory complaints in subjective cognitive
      impairment.
AB  - Subjective cognitive impairment (SCI) is a clinical state characterized by
      subjective cognitive deficits without cognitive impairment. To test the
      hypothesis that this state might involve dysfunction of self-referential
      processing mediated by cortical midline structures, we investigated abnormalities
      of functional connectivity in these structures in individuals with SCI using
      resting-state functional magnetic resonance imaging. We performed functional
      connectivity analysis for 23 individuals with SCI and 30 individuals without SCI.
      To reveal the pathophysiological basis of the functional connectivity change, we
      performed magnetic resonance-diffusion tensor imaging. Positron emission
      tomography-amyloid imaging was conducted in 13 SCI and 15 nonSCI subjects.
      Individuals with SCI showed reduced functional connectivity in cortical midline
      structures. Reduction in white matter connections was related to reduced
      functional connectivity, but we found no amyloid deposition in individuals with
      SCI. The results do not necessarily contradict the possibility that SCI indicates
      initial cognitive decrements, but imply that reduced functional connectivity in
      cortical midline structures contributes to overestimation of the experience of
      forgetfulness.

PMID- 25862422
TI  - Investigating stereotypes of social anxiety.
AB  - BACKGROUND AND OBJECTIVES: This paper consists of two studies that test for the
      presence and content of stereotypes of highly socially anxious individuals.
      DESIGN: The current studies examined traits that comprise social anxiety
      stereotypes, and then tested whether undergraduate students held part of this
      stereotype via an implicit-association test (IAT). METHODS: In Study 1, a sample
      of undergraduate students (n = 635) was asked to generate descriptors of people
      who are highly socially anxious. These descriptors were utilized to create the
      Social Anxiety Stereotype Measure (SASM) and the underlying factor structure of
      the SASM was analyzed. In Study 2, a different sample of undergraduate students
      (n = 87) was given an IAT to further test for the presence of one of the factors
      obtained in Study 1. RESULTS: Factor analyses indicated the presence of two
      social anxiety stereotypes: social inhibition and oddity (comparative fit index =
      .97, Tucker-Lewis Index = .95, root mean square error of approximation = .07,
      standardized root mean square residual = .06). Oddity as a stereotype of social
      anxiety was further supported via an IAT: Participants reacted more quickly when
      oddity (vs. normality) words were paired with social anxiety (vs. social
      confidence) words (D = -1.15, SD = .26; t(85) = -41.50, p < .001). CONCLUSIONS:
      Factor analyses revealed two social anxiety stereotypes: social inhibition and
      oddity. Further testing of the oddity stereotype was supported via an IAT.

PMID- 25862423
TI  - Factors affecting abundance and prevalence of blood fluke, Cardicola forsteri,
      infection in commercially ranched southern bluefin tuna, Thunnus maccoyii, in
      Australia.
AB  - A survey of blood fluke, Cardicola forsteri, infection in ranched southern
      bluefin tuna, Thunnus maccoyii, was undertaken over three farming seasons, from
      March 2004 to September 2006. Analyses of covariance and logistic regression were
      used to explore the effects of company, year, season, time in culture, and
      condition index on intensity, abundance and prevalence of blood fluke infection.
      Average prevalence of blood fluke infection was 62.64% over the period of the
      survey. Average intensity was 6.20 (+/- 0.57) fluke per infected host and the
      average abundance was 3.70 (+/- 0.57) fluke per host. Year did not influence mean
      intensity or abundance although a significant decrease in prevalence in 2005 was
      evident. Tuna harvested in winter had a significantly greater abundance and
      prevalence of blood fluke than the tuna harvested in autumn. No effect of
      intensity or abundance of infection was observed on the condition of the infected
      tuna. A universal factor in explaining variation in C. forsteri intensity,
      abundance and prevalence was company. Differences in infection levels between
      tuna from different companies may be related to differences in husbandry measures
      employed on each farm, or due to different average sizes of tuna farmed by each
      of the companies, or due to the location of the operations.

PMID- 25862424
TI  - Pulmonary hypertension and hepatic cirrhosis.
AB  - Pulmonary hypertension is a relatively common phenomenon in patients with hepatic
      cirrhosis and can appear through various mechanisms. The most characteristic
      scenario that binds portal and pulmonary hypertension is portopulmonary syndrome.
      However, hyperdynamic circulation, TIPS placement and heart failure can raise the
      mean pulmonary artery pressure without increasing the resistances. These
      conditions are not candidates for treatment with pulmonary vasodilators and
      require a specific therapy. A correct assessment of hemodynamic, ultrasound and
      clinical variables enables the differential diagnosis of each situation that
      produces pulmonary hypertension in patients with cirrhosis. 

PMID- 25862425
TI  - Price-transparency and cost accounting: challenges for health care organizations
      in the consumer-driven era.
AB  - Health care reform is directed toward improving access and quality while
      containing costs. An essential part of this is improvement of pricing models to
      more accurately reflect the costs of providing care. Transparent prices that
      reflect costs are necessary to signal information to consumers and producers.
      This information is central in a consumer-driven marketplace. The rapid increase
      in high deductible insurance and other forms of cost sharing incentivizes the
      search for price information. The organizational ability to measure costs across
      a cycle of care is an integral component of creating value, and will play a
      greater role as reimbursements transition to episode-based care, value-based
      purchasing, and accountable care organization models. This article discusses use
      of activity-based costing (ABC) to better measure the cost of health care. It
      describes examples of ABC in health care organizations and discusses impediments
      to adoption in the United States including cultural and institutional barriers. 

PMID- 25862426
TI  - Perceiving expressions of emotion: What evidence could bear on questions about
      perceptual experience of mental states?
AB  - What evidence could bear on questions about whether humans ever perceptually
      experience any of another's mental states, and how might those questions be made
      precise enough to test experimentally? This paper focusses on emotions and their
      expression. It is proposed that research on perceptual experiences of physical
      properties provides one model for thinking about what evidence concerning
      expressions of emotion might reveal about perceptual experiences of others'
      mental states. This proposal motivates consideration of the hypothesis that
      categorical perception of expressions of emotion occurs, can be facilitated by
      information about agents' emotions, and gives rise to phenomenal expectations. It
      is argued that the truth of this hypothesis would support a modest version of the
      claim that humans sometimes perceptually experience some of another's mental
      states. Much available evidence is consistent with, but insufficient to
      establish, the truth of the hypothesis. We are probably not yet in a position to
      know whether humans ever perceptually experience others' mental states. 

PMID- 25862427
TI  - Conflict resolved: On the role of spatial attention in reading and color naming
      tasks.
AB  - The debate about whether or not visual word recognition requires spatial
      attention has been marked by a conflict: the results from different tasks yield
      different conclusions. Experiments in which the primary task is reading based
      show no evidence that unattended words are processed, whereas when the primary
      task is color identification, supposedly unattended words do affect processing.
      However, the color stimuli used to date does not appear to demand as much spatial
      attention as explicit word reading tasks. We first identify a color stimulus that
      requires as much spatial attention to identify as does a word. We then
      demonstrate that when spatial attention is appropriately captured, distractor
      words in unattended locations do not affect color identification. We conclude
      that there is no word identification without spatial attention. 

PMID- 25862428
TI  - The use of low-volume polyethylene glycol containing ascorbic acid versus 2 L of
      polyethylene glycol plus bisacodyl as bowel preparation for colonoscopy.
AB  - OBJECTIVE: Low-volume polyethylene glycol (PEG) bowel preparations have been
      developed to improve compliance for colonoscopy. Our study aimed to compare the
      efficacy and tolerability of low-volume PEG containing ascorbic acid for
      colonoscopy against 2 L of PEG plus bisacodyl. METHODS: We prospectively enrolled
      consecutive inpatients who had not undergone polypectomy at the index colonoscopy
      and were subsequently referred for polypectomy at our hospital. A total of 62
      patients were randomized to receive either low-volume PEG containing ascorbic
      acid (n = 31) or 2 L of PEG plus bisacodyl (n = 31) as a split-dose regimen in
      inpatients. The efficacy of preparation was determined using the Ottawa Bowel
      Preparation Score (OBPS) and a 4-point scale. Adverse events, tolerability, and
      willingness were evaluated using a questionnaire. RESULTS: Based on the OBPS and
      4-point scale, we determined that the efficacy of low-volume PEG containing
      ascorbic acid was comparable to that of the 2 L of PEG plus bisacodyl (p = 0.071
      for OBPS, p = 0.056 for the 4-point scale). Adverse events were comparable
      between the two groups (p = 1.000). A greater proportion of patients in the low
      volume PEG containing ascorbic acid (90.6%) and the 2L of PEG plus bisacodyl
      (96.9%) were willing to repeat the same preparation for subsequent colonoscopy.
      CONCLUSION: Low-volume PEG containing ascorbic acid had comparable efficacy and
      tolerability to 2 L of PEG plus bisacodyl, when given as a split dose, for
      colonoscopy in inpatients. Split-dose low-volume PEG containing ascorbic acid is
      a good alternative for bowel preparation for colonoscopy in inpatients.

PMID- 25862430
TI  - Long-term arsenic monitoring with an Enterobacter cloacae microbial fuel cell.
AB  - A microbial fuel cell was constructed with biofilms of Enterobacter cloacae grown
      on the anode. Bioelectrocatalysis was observed when the biofilm was grown in
      media containing sucrose as the carbon source and methylene blue as the mediator.
      The presence of arsenic caused a decrease in bioelectrocatalytic current. Biofilm
      growth in the presence of arsenic resulted in lower power outputs whereas
      addition of arsenic showed no immediate result in power output due to the short
      term arsenic resistance of the bacteria and slow transport of arsenic across
      cellular membranes to metabolic enzymes. Calibration curves plotted from the
      maximum current and maximum power of power curves after growth show that this
      system is able to quantify both arsenate and arsenate with low detection limits
      (46 MUM for arsenate and 4.4 MUM for arsenite). This system could be implemented
      as a method for long-term monitoring of arsenic concentration in environments
      where arsenic contamination could occur and alter the metabolism of the organisms
      resulting in a decrease in power output of the self-powered sensor.

PMID- 25862429
TI  - Prediction of future falls in a community dwelling older adult population using
      instrumented balance and gait analysis.
AB  - BACKGROUND: The role of instrumented balance and gait assessment when screening
      for prospective fallers is currently a topic of controversial discussion.
      OBJECTIVES: This study analyzed the association between variables derived from
      static posturography, instrumented gait analysis and clinical assessments with
      the occurrence of prospective falls in a sample of community dwelling older
      people. METHODS: In this study 84 older people were analyzed. Based on a
      prospective occurrence of falls, participants were categorized into fallers and
      non-fallers. Variables derived from clinical assessments, static posturography
      and instrumented gait analysis were evaluated with respect to the association
      with the occurrence of prospective falls using a forward stepwise, binary,
      logistic regression procedure. RESULTS: Fallers displayed a significantly shorter
      single support time during walking while counting backwards, increased
      mediolateral to anteroposterior sway amplitude ratio, increased fast mediolateral
      oscillations and a larger coefficient (Coeff) of sway direction during various
      static posturography tests. Previous falls were insignificantly associated with
      the occurrence of prospective falls. CONCLUSION: Variables derived from
      posturography and instrumented gait analysis showed significant associations with
      the occurrence of prospective falls in a sample of community dwelling older
      adults.

PMID- 25862431
TI  - Effects of atmospheric air plasma treatment of graphite and carbon felt
      electrodes on the anodic current from Shewanella attached cells.
AB  - The attachment of electrochemically active microorganisms (EAM) on an electrode
      is determined by both the chemistry and topography of the electrode surface. Pre
      treatment of the electrode surface by atmospheric air plasma introduces
      hydrophilic functional groups, thereby increasing cell attachment and
      electroactivity in short-term experiments. In this study, we use graphite and
      carbon felt electrodes to grow the model EAM Shewanella loihica PV-4 at oxidative
      potential (0.2 V vs. Ag/AgCl). Cell attachment and electroactivity are measured
      through electrodynamic methods. Atmospheric air plasma pre-treatment increases
      cell attachment and current output at graphite electrodes by 25%, while it
      improves the electroactivity of the carbon felt electrodes by 450%. Air plasma
      pre-treatment decreased the coulombic efficiency on both carbon felt and graphite
      electrodes by 60% and 80%, respectively. Microbially produced flavins adsorb
      preferentially at the graphite electrode, and air plasma pre-treatment results in
      lower flavin adsorption at both graphite and carbon felt electrodes. Results show
      that air plasma pre-treatment is a feasible option to increase current output in
      bioelectrochemical systems.

PMID- 25862432
TI  - Prevalence, size and distribution of microdamage in the human otic capsule.
AB  - CONCLUSIONS: Age-dependent microdamage (MDx) accumulates excessively in human
      perilabyrinthine bone, where the bone turnover is almost absent. This may have
      pathological implications for bone-specific disorders such as otosclerosis. The
      role of MDx accumulation is discussed from an osteodynamic perspective.
      OBJECTIVES: Bone remodelling is highly inhibited within the otic capsule compared
      with the rest of the skeleton. Consequently excessive accumulation of age
      dependent capsular MDx is expected. This study describes the prevalence, size and
      topographical distribution of MDx in the human otic capsule. METHODS: A total of
      241 undecalcified human temporal bones were examined. Bulk staining and the
      cutting-grinding technique were used to separate in vivo MDx from microcrack
      artefacts induced post mortem by the milling procedure. Quantitative data were
      obtained by fluorescence microscopy by counting and measuring and by the use of
      stereology. RESULTS: Microcracks accumulated continuously and extensively in the
      human otic capsule throughout life. Both the number and total length of MDx were
      higher close to the inner ear space as compared with the capsular periphery. The
      mean length of the MDx remained constant with age. There was no statistically
      significant sex difference.

PMID- 25862433
TI  - Cultural capital and smoking in young adults: applying new indicators to explore
      social inequalities in health behaviour.
AB  - BACKGROUND: Associations between social status and health behaviours are well
      documented, but the mechanisms involved are less understood. Cultural capital
      theory may contribute to a better understanding by expanding the scope of
      inequality indicators to include individuals' knowledge, skills, beliefs and
      material goods to examine how these indicators impact individuals' health
      lifestyles. We explore the structure and applicability of a set of cultural
      capital indicators in the empirical exploration of smoking behaviour among young
      male adults. METHODS: We analysed data from the Swiss Federal Survey of
      Adolescents (CH-X) 2010-11 panel of young Swiss males (n = 10 736). A set of nine
      theoretically relevant variables (including incorporated, institutionalized and
      objectified cultural capital) were investigated using exploratory factor
      analysis. Regression models were run to observe the association between factor
      scores and smoking outcomes. Outcome measures consisted of daily smoking status
      and the number of cigarettes smoked by daily smokers. RESULTS: Cultural capital
      indicators aggregated in a three-factor solution representing 'health values',
      'education and knowledge' and 'family resources'. Each factor score predicted the
      smoking outcomes. In young males, scoring low on health values, education and
      knowledge and family resources was associated with a higher risk of being a daily
      smoker and of smoking more cigarettes daily. CONCLUSION: Cultural capital
      measures that include, but go beyond, educational attainment can improve
      prediction models of smoking in young male adults. New measures of cultural
      capital may thus contribute to our understanding of the social status-based
      resources that individuals can use towards health behaviours.

PMID- 25862434
TI  - Erratum to: Six years ahead: a longitudinal analysis regarding course and
      predictive value of the Strengths and Difficulties Questionnaire (SDQ) in
      children and adolescents.
AB  - Erratum to: Eur Child Adolesc PsychiatryDOI 10.1007/s00787-014-0640-x
      Unfortunately, the names of two authors, Ulrike Ravens- Sieberer and Fionna
      Klasen, were omitted in the original publication of the article. Please find the
      correct author list below:Andreas Becker . Aribert Rothenberger . Alexander Sohn
      . Ulrike Ravens-Sieberer . Fionna Klasen . The BELLA study group

PMID- 25862435
TI  - Attitudes Toward Mental Health Services Among American Indians by Two Age Groups.
AB  - This study examined determinants of attitudes toward mental health services with
      a sample of American Indian younger-old-adults (aged 50-64, n = 158) and American
      Indian older-old adults (aged 65 and older, n = 69). Adapting Andersen's
      behavioral model of healthcare utilization, predisposing factors, mental health
      needs, and enabling factors were considered as potential predictors. Female and
      those with higher levels of social support tend to report more positive attitudes
      toward mental health services. Culture-influenced personal belief was associated
      with negative attitudes toward mental health services among American Indian
      younger-old -adults. Age and higher chronic medical conditions were significantly
      related to negative attitudes toward mental health services. Health insurance was
      positively associated with positive attitudes toward mental health services in
      the American Indian older-old adults. Findings indicate that practitioners should
      engage how culture, social support, and chronic conditions influence the response
      to mental health needs when working with older American Indians.

PMID- 25862436
TI  - Direct oral anticoagulants in the secondary prevention of stroke and transient
      ischemic attack in patients with atrial fibrillation.
AB  - In patients with non-valvular atrial fibrillation (NVAF) and history of transient
      ischemic attack (TIA) or stroke, the rate of vascular events is higher in
      comparison to patients without history of stroke or TIA. A meta-analysis of
      direct oral anticoagulants (DOACs) studies, including only patients with history
      of stroke or TIA, report a significant reduction of 15 % in the rates of
      composite of stroke and systemic embolism in patients treated with DOACs,
      compared to those treated with warfarin. Furthermore, a reduction of 14 % for
      major bleeding, as well as a 56 % reduction for hemorrhagic stroke over a median
      follow-up of 1.8-2.0 years is reported. The combination of DOACs and antiplatelet
      agents carries the potential of additive benefits in patients with NVAF and other
      vascular diseases. However, the rate of major bleeding is higher among patients
      who receive concomitantly antiplatelet agents, compared to those taking only a
      single drug category. The risk of major bleeding seems to be higher among
      patients receiving dual antiplatelet agents, compared to those receiving a single
      antiplatelet drug. When NVAF is associated with an acute coronary syndrome
      requiring dual antiplatelet therapy (e.g. coronary angioplasty and stenting),
      DOACs plus this therapy should be considered. However, this therapy has to be
      administered for the shortest possible time, according to the patient's
      haemorrhagic and thrombotic risks, and stent type. When NVAF is associated with
      carotid stenosis, a single antiplatelet therapy should be considered. Regarding
      carotid revascularization, it seems preferable to treat these patients with
      endarterectomy, so to avoid dual antiplatelet therapy, which is generally
      administered after stenting.

PMID- 25862437
TI  - Sensing and responding to cytosolic viruses invasions: An orchestra of
      kaleidoscopic ubiquitinations.
AB  - Ubiquitin is a versatile molecular signature that modulates diverse cellular
      processes via proteasome-dependent and proteasome-independent mechanisms. The
      covalent and/or non-covalent binding of mono-ubiquitin and/or poly-ubiquitin
      chains to a target protein broadens the dynamic and functional spectra for signal
      integration. Different linkages of poly-ubiquitin chains determine specific
      physiological or pathological functions of target proteins. Accumulating
      evidences has revealed the essential roles of ubiquitination in orchestrating the
      host defenses against cytosolic RNA or DNA from viral infections. In this review,
      we summarize the current progress regarding the understanding of ubiquitin
      mediated regulation of the RIG-I and STING antiviral signaling pathways and
      discuss certain critical issues that remain to be resolved in future studies. 

PMID- 25862438
TI  - Prioritizing precision medicine for prostate cancer.

PMID- 25862440
TI  - Health 2020 - achieving health and development in today's Europe.

PMID- 25862439
TI  - Dynamic prediction in breast cancer: proving feasibility in clinical practice
      using the TEAM trial.
AB  - BACKGROUND: Predictive models are an integral part of current clinical practice
      and help determine optimal treatment strategies for individual patients. A
      drawback is that covariates are assumed to have constant effects on overall
      survival (OS), when in fact, these effects may change during follow-up (FU).
      Furthermore, breast cancer (BC) patients may experience events that alter their
      prognosis from that time onwards. We investigated the 'dynamic' effects of
      different covariates on OS and developed a nomogram to calculate 5-year dynamic
      OS (DOS) probability at different prediction timepoints (tP) during FU. METHODS:
      Dutch and Belgian postmenopausal, endocrine-sensitive, early BC patients enrolled
      in the TEAM trial were included. We assessed time-varying effects of specific
      covariates and obtained 5-year DOS predictions using a proportional baselines
      landmark supermodel. Covariates included age, histological grade, hormone
      receptor and HER2 status, T- and N-stage, locoregional recurrence (LRR), distant
      recurrence, and treatment compliance. A nomogram was designed to calculate 5-year
      DOS based on individual characteristics. RESULTS: A total of 2602 patients were
      included (mean FU 6.2 years). N-stage, LRR, and HER2 status demonstrated time
      varying effects on 5-year DOS. Hazard ratio (HR) functions for LRR, high-risk N
      stage (N2/3), and HER2 positivity were HR = (8.427 * 0.583[Formula: see text], HR
      = (3.621 * 0.816[Formula: see text], and HR = (1.235 * 0.851[Formula: see text],
      respectively. Treatment discontinuation was associated with a higher mortality
      risk, but without a time-varying effect [HR 1.263 (0.867-1.841)]. All other
      covariates were time-constant. DISCUSSION: The current nomogram accounts for
      elapsed time since starting adjuvant endocrine treatment and optimizes prediction
      of individual 5-year DOS during FU for postmenopausal, endocrine-sensitive BC
      patients. The nomogram can facilitate in determining whether further therapy will
      benefit an individual patient, although validation in an independent dataset is
      still needed.

PMID- 25862441
TI  - 60th anniversary of state sanitary inspection and 95th anniversary of sanitary
      services in Poland.
AB  - 2014 was a year of two jubilees in the remit of public health in Poland: 95th
      anniversary of sanitary services and 60th anniversary of State Sanitary
      Inspection. It was an opportunity to organize a conference so as to remind the
      events concerning a birth of the institution which, after the First World War,
      had originated structures of epidemiological and sanitary supervision in Poland,
      the one we have nowadays. A conference took place on 16th December 2014 in
      Warsaw, at Palladium Theatre.

PMID- 25862442
TI  - Selected aspects of filoviruses in the view of Ebola virus disease epidemic.
AB  - Ebola virus disease (EVD) is a zoonosis of high virulence in humans. Current
      epidemic in West Africa is the largest EVD epidemic reported so far, exceeding
      the number of cases notified and geographical regions affected. This article
      discusses selected aspects of Ebola virus biology and ecology which are of
      significance for the processes of primary infection in humans and the spread of
      epidemic in population. A special attention was drawn to the issues essential for
      the diagnosis of infection and safety of testing.

PMID- 25862443
TI  - Neoehrlichiosis - a new tick-borne disease - is there a threat in Poland?
AB  - Recently in a few European countries a new pathogen transmitted by ticks Ixodes
      ricinus - Candidatus Neoehrlichia mikurensis was identified. It is a Gram
      negative intracellular bacterium belonging to the Anaplasmataceae family.
      Worldwide 23 cases were described, among which 16 in Europe. Infection with
      Candidatus Neoehrlichia mikurensis in humans runs mainly with fever, headache,
      nausea, arthralgia, thrombotic or haemorrhagic lesions, subcutaneous
      haemorrhages, haemorrhagic rash, general malaise, weight loss. The course of
      infection may be acute or chronic. The diagnosis is based on TaqMan real-time
      PCR, which allows for the detection of the gene coding for 16S rRNA and a blood
      smear. The drug of choice is doxycycline. Due to the fact that the Ixodes ricinus
      ticks are common in Poland, there is a probability of infection with Candidatus
      Neoehrlichia mikurensis among patients bitten by ticks. The possibility of non
      symptomatic human infection Candidatus Neoehrlichia mikurensis in north-eastern
      Poland was shown, confirming the necessity to conduct research on a larger scale.
      Moreover, awareness of physicians about the possibility of infection in patients
      with non-specific symptoms after tick bite should be increased.

PMID- 25862444
TI  - Impact of vaccination against HBV on hepatitis B incidence in Opolskie province
      in 2007-2011.
AB  - OBJECTIVE: This article aimed at evaluating the impact of HBV vaccination in
      population included and not listed in the National Immunization Programme (NIP)
      on hepatitis B incidence in Opolskie province in 2007 - 2011. MATERIALAND
      METHODS: Analysis was based on data provided by the Sanitary and Epidemiological
      Inspection under epidemiological surveillance conducted, i.e. MZ-56, MZ-57
      reports (reports on cases of infectious diseases), MZ-54 reports (reports on
      vaccinations) and 'Questionnaires on hepatitis type B and C'. A total of 446
      records of detected and confirmed hepatitis B cases, registered in 2007-2011 in
      district sanitary and epidemiological stations, were subject to analysis.
      RESULTS: In 2007-2011, hepatitis B incidence in Opolskie province was higher
      compared to the average incidence in Poland and was increasing in the successive
      years (5.8; 6.6; 7.9; 11.8; 11.0 per 100,000 population). An increase of
      incidence resulted from increasing number of patients with chronic hepatitis B
      (chronic HBV), i.e. from 47 in 2007 to 119 in 2010 and 110 in 2011 compared to
      decreasing number of acute infections (acute HBV). In the analyzed period, no new
      infections were reported in the following age group 0-9 years in Opolskie
      province. Only 3 cases (chronic stage) were noted in the age group 10-14 years.
      Of 446 patients, diagnosed with hepatitis B, 309 (69.3%) were not vaccinated. The
      remaining cases of acute or chronic hepatitis B were vaccinated, including 124
      (27.8%) and 13 individuals with complete and incomplete vaccination,
      respectively. CONCLUSIONS: This analysis suggests an important role of HBV
      vaccination in the prevention of HBV infections. In case of individuals at the
      age older than that specified in the NIP, especially adults, it is recommended to
      perform diagnostic tests for HBV infection prior to vaccination. Furthermore, it
      is required to undertake activities aimed at promoting HBV vaccination in
      populations which are not included in the NIP.

PMID- 25862445
TI  - Incidence of healthcare-associated gastroenteritis in children hospitalized on
      paediatric ward in provincial hospital in 2007-2013.
AB  - OBJECTIVE: This article aimed at evaluating the incidence and distribution of
      healthcare-associated (HAI) gastroenteritis (GE) in patients hospitalized on
      paediatric ward in St. Lukas Provincial Hospital in Tarnow. INTRODUCTION:
      Gastroenteritis remains a common manifestation of healthcare-associated
      infections on paediatric wards. In Poland, there are limited data on the
      proportion of healthcare-associated GE in the epidemiology of healthcare
      associated infections. It was decided to present the incidence and etiology of
      these infections in a 7 year study period. METHODS: For the purpose of this
      study, standard definitions of healthcare-associated infections issued by the
      European Centre for Disease Prevention and Control (ECDC) were adopted.
      Cumulative incidence rates and incidence density rates were calculated. RESULTS:
      A total of 11,966 records of children hospitalized in 2007-2013 were subject to
      analysis. In this period, 251 healthcare-associated gastroenteritis cases of
      viral etiology were identified. For these infections, cumulative incidence rate
      (CIR) and incidence density rate (IDR) were 2.11% and 3.37/1,000 person-days,
      respectively. GE was most frequently reported in children aged less than 2 years
      (average - 1.6, SD - 2.1). Average hospitalization of a child who was not
      diagnosed with healthcare-associated GE was 6.2 days while for GE case it
      amounted to 11.2 days. GE was equally present in girls and boys, i.e. 2.1%.
      Rotavirus-induced GE was the most commonly diagnosed (GE-RV - Rotavirus
      Gastroenteritis). Such virus was identified in 189 children (CIR - 1.58%, IDR -
      2.51/1,000 person-days). Rotavirus GE was followed by concomitant infections with
      rotaviruses and adenoviruses. A total of 12 patients were diagnosed with such co
      infection (CIR - 0.10%, IDR - 0.16/1,000 person-days). Infections caused by
      adenoviruses (GE-AV - Adenovirus Gastroenteritis) occurred in 7 patients (CIR -
      0.06%, IDR - 0.09/1,000 person-days). For 43 (17%) children, etiological agents
      of healthcare-associated GE were not determined. SUMMARY: Rotaviruses were the
      most commonly identified etiological agents of healthcare-associated
      gastroenteritis on paediatric ward. Children aged less than 2 years were those
      most frequently affected.

PMID- 25862446
TI  - Clinical and epidemiological characteristics of males with syphilis in Bialystok,
      Poland in 2008-2013.
AB  - INTRODUCTION: Men who have sex with men (MSM) contribute disproportionally to the
      spread of several sexually transmitted infections (STIs) in many European and
      other industrialised countries. OBJECTIVE: To describe and compare clinical and
      epidemiological data on MSM and men who have sex with women (MSW) treated for
      syphilis in Bialystok, Poland in 2008-2013. MATERIAL AND METHODS: Analyzed
      characteristics included the age, residency, marital status, professional
      activity, number of sexual contacts, relation to the source contact, stage of
      syphilis, concomitant STIs including HIV, adherence to follow-up visits and
      efficacy of partner notification and contact tracing. RESULTS: Among 49 male
      patients with syphilis, 19 (38.8%) were MSM. The average age of MSM and MSW was
      31.9 and 31.3 years (P>0.05), respectively. The majority of patients in both
      groups were residents of urban areas and single. More than five lifetime sexual
      partners were declared by 47.4% of MSM and 16.7% of MSW (P = 0.01), and 73.7% and
      60.0%, respectively (P>0.05), had only casual sexual relationship or steady
      partner but with additional casual sexual contact(s). Most of the syphilis cases
      were diagnosed during early symptomatic stage (in 84.2% of MSM and 56.7% of MSW;
      P>0.05). Other concomitant STIs were detected in 26.3% of MSM and 10.0% of MSW
      (P>0.05), and HIV infection - in 15.8% and 3.0% (P>0.05), respectively. Partner
      notification and contact tracing was not possible in 31.6% of MSM and 23.3% of
      MSW (P>0.05), and 21.1% MSM and 40.0% MSW (P>0.05) did not attend any follow-up
      visits. CONCLUSIONS: MSM constituted a substantial proportion of male patients
      with syphilis, had more sexual contacts, including casual contacts, and more
      concomitant STIs, including HIV compared to MSW. The follow-up and contact
      tracing was suboptimal in MSM but also in MSW. Taking into consideration the
      important role of MSM in the spread of STIs, including syphilis, it is crucial to
      continue the present study but also to conduct similar investigations on national
      level.

PMID- 25862447
TI  - Current views on the persistence of immunity following hepatitis B vaccination.
AB  - This paper presents current views on the persistence of immunity following
      vaccination against hepatitis B. Very high effectiveness of hepatitis B
      vaccination has been reported in a number of studies worldwide. Standard
      vaccination with approved schedule induces protective antibody titers in healthy
      newborns, children, adolescents and adults in more than 96% and 90% of cases,
      respectively. A number of studies have also confirmed the occurrence of
      anamnestic response to a booster injection of HB vaccine even after 20 years
      following primary immunization. From the numerous studies transpires that
      cellular response following hepatitis B vaccination persists longer compared to
      humoral response. Irrespective of gradual decline and loss of anti-HBs
      antibodies, adequately performed primary immunization in healthy persons ensures
      long-term protection against acute and chronic stages of hepatitis B. In fact, T
      and B lymphocytes, whose responsiveness prevails the presence of anti-HBs
      antibodies in serum, are true markers of immunity. A special attention should be
      given to persons with secondary immunodeficiencies or immunosuppressed patients
      whose immunization against hepatitis B raises difficulties.

PMID- 25862448
TI  - Evaluation of human papilloma virus (HPV) vaccination strategies and vaccination
      coverage in adolescent girls worldwide.
AB  - STUDY OBJECTIVE: An analysis of HPV vaccination strategies and vaccination
      coverage in adolescent girls worldwide for the last eight years with regard to
      potential improvement of vaccination coverage rates in Poland. METHODS:
      Literature search, covering the period 2006-2014, was performed using Medline.
      Comparative analysis of HPV vaccination strategies and coverage between Poland
      and other countries worldwide was conducted. RESULTS: In the last eight years, a
      number of countries introduced HPV vaccination for adolescent girls to their
      national immunization programmes. Vaccination strategies differ, consequently
      affecting vaccination coverage, ranging from several percent to more than 90%.
      Usually, there are also disparities at national level. The highest HPV
      vaccination coverage rates are observed in countries where vaccines are
      administered in school settings and funded from the national budget. Poland is
      one of the eight EU countries where HPV vaccination has not been introduced to
      mandatory immunization programme and where paid vaccination is only provided in
      primary health care settings. HPV vaccination coverage in adolescent girls is
      estimated at 7.5-10%. CONCLUSIONS: Disparities in HPV vaccination coverage rates
      in adolescent girls worldwide may be due to different strategies of vaccination
      implementation between countries. Having compared to other countries, the low HPV
      vaccination coverage in Polish adolescent girls may result from the lack of
      funding at national level and the fact that vaccines are administered in a
      primary health care setting. A multidimensional approach, involving the
      engagement of primary health care and school personnel as well as financial
      assistance of government at national and local level and the implementation of
      media campaigns, particularly in regions with high incidence of cervical cancer,
      could result in an increase of HPV vaccination coverage rates in Poland.

PMID- 25862449
TI  - Thiomersal-containing vaccines - a review of the current state of knowledge.
AB  - Thiomersal is an organomercury compound known for its antiseptic and antifungal
      properties and used as an antibacterial agent in pharmaceutical products,
      including vaccines and other injectable biological products. In recent years,
      concerns about the possible link between immunization with thiomersal-containing
      vaccines and autism development have grown. Many case-control and cohort studies
      have been conducted on a number of populations, and none of them have confirmed
      the hypothetical relation between thiomersal and increased risk of autism
      spectrum disorders (ASDs) development. It is also confirmed by the fact, that
      since 1999, number of thiomersal-containing vaccines used worldwide is decreasing
      year by year, while the prevalence of ASDs cases is rising. There are no
      contraindications to the use of vaccines with thiomersal in infants, children and
      non-pregnant women. The risk of serious complications associated with the
      development of diseases in unvaccinated individuals far outweighs the potential
      risk of adverse consequences associated with immunization with thiomersal
      containing vaccines.

PMID- 25862450
TI  - Prostate cancer incidence in Podkarpackie province in 2002-2011.
AB  - INTRODUCTION: Prostate cancer is an important epidemiological problem in
      Podkarpackie province. A significant rise in the number of new cases was
      reported. The values of crude and standardized rates, percentage share and
      cumulative risk also increased. OBJECTIVE: This article aims at analyzing
      incidence and mortality rates of prostate cancer in 2002-2011. MATERIAL AND
      METHODS: Analysis was based on data retrieved from the Podkarpackie Cancer
      Registry in Rzeszow. A total of 4 263 prostate cancer cases and 2 032 fatal cases
      were analyzed from the list of orderly arranged patients. Crude and standardized
      rates of incidence and mortality, cumulative risk and percentage share of
      prostate cancer out of all cancers were calculated. RESULTS: Compared to 2002,
      the number of cases increased by 150.5% in 2011. Cumulative risk rose from 1.8%
      in 2002 to 4.7% in 2011. Percentage of prostate cancer cases out of all
      registered cancers increased more than twofold in the analyzed decade. There was
      a 22.3% increase in the number of fatal cases due to prostate cancer, accompanied
      by a slight decrease of standardized mortality rate from 13.2/100 000 in 2002 to
      12.6/100 000 in 2011. In the analyzed period, 41.8% of patients were diagnosed
      with locally adavanced prostate cancer.

PMID- 25862451
TI  - Perceived barriers to physical activity among Polish adolescents.
AB  - OBJECTIVE: To identify barriers to physical activity (PA) for adolescents
      according to the gender and age and examine the association between these
      barriers and youths' physical activity. SUBJECTAND METHODS: 3346 students aged 10
      16 years (1759 girls) took part in the cross-sectional, nationally representative
      study. For this paper the dataset was created from adolescents who reported
      perceived barriers to PA, N = 2300, (1259 girls), range 13-16 years. Barriers and
      physical activity (MVPA) were analysed for all participants, as well as by
      gender, age group and place of residence. Multiple regression analysis was used
      to examine the relationships between perceived barriers and physical inactivity
      for all and than separately for boys and girls. RESULTS: Lack of energy, lack of
      time and lack of support were three of the five barriers reported by more than
      40% of adolescents, statistically more likely by girls than boys and older youth
      than younger. For boys - lack of time (OR = 2.56; CI = 1.66-3.96), lack of skills
      (OR = 2.35; CI = 1.94-3.95), lack of willpower (OR = 1.71, CI = 1.05-2.80) and
      lack of support (OR = 1.64, CI = 1.11-2.41) were the predictors contributing to
      low level of PA. For girls lack of skills (OR = 3.16, CI = 1.62-6.18), lack of
      energy (OR = 1.84, CI = 1.14-2.96), lack of support (OR = 1.64, CI = 1.07-2.54)
      and lack of time (OR = 1.61,CI = 1.00-2.60) were positively and statistically
      significant associated with physical inactivity. CONCLUSIONS: 1. Perceived
      barriers to physical activity among adolescents have strong negative impact on
      recommended PA level. For girls lack of skills is the strongest predictor of low
      PA, for boys - lack of time. 2. Identification more precisely barriers to
      physical activity among adolescents will enable to developed more effective
      interventions in high-risk populations.

PMID- 25862452
TI  - Cardiovascular disease (CVD) risk factors in Krakow and in the whole Poland adult
      population. Results from the WOBASZ study and Polish arm of the HAPIEE project.
AB  - In Krakow, the second largest town in Poland, cardiovascular disease (CVD)
      mortality rate is lower than in most top largest towns in Poland and lower than
      the rate for total Polish population. AIM: The aim of the present analysis was to
      compare socioeconomic status (SES), prevalence of CVD risk factors and SCORE
      assessment of risk in Krakow with residents of other big towns in Poland and with
      general Polish population. MATERIALAND METHODS: We used data from the two large,
      population studies which used comparable methods for risk factors assessment: 1)
      Polish part of the HAPIEE Project in which 10 615 residents of Krakow at age
      between 45-69 years were examined, and (2) The WOBASZ Study which contributed
      with a sub-sample 6 888 of residents of Poland at corresponding age group. WOBASZ
      sample included 992 residents of big towns other than Krakow. Age-standardized
      proportions of persons with CVD risk factors were compared between Krakow and the
      other big towns in Poland and between Krakow and the whole Poland using chi2
      test. RESULTS: The striking observation was that in Krakow proportions of
      participants with university education were substantially higher than average for
      the other big towns and the whole Poland. Also, the proportion of occupationally
      active men and women was the highest in Krakow. In both sexes, prevalence of
      smoking, hypercholesterolemia and hypertension in Krakow was similar to the other
      big towns but the prevalence of hypercholesterolemia and hypertension (in men
      only) was lower than average for Poland. The distribution by SCORE risk
      categories were similar in all three samples studied. In general, the
      distribution by BMI categories was less favourable but the prevalence of central
      obesity was lower among residents of Krakow than among residents of the other big
      towns and citizens of the whole Poland. Prevalence of diabetes was higher in
      Krakow than in the other samples studied. The differences between population of
      Krakow and population of other parts of Poland in the exposure to the main risk
      factors were found diverse and not big enough to be followed by differences in
      the distribution by the categories of SCORE risk assessment. The study suggested
      the importance of obesity and diabetes which are not used for the SCORE risk
      assessment and especially the importance of psychosocial and economic factors
      which may influence CVD risk and contribute more to the explanation of the
      regional differences in CVD mortality.

PMID- 25862453
TI  - The regional variation in tobacco smoking - attributable mortality in Poland,
      2006-2010.
AB  - STUDY OBJECTIVE: To explain the regional variation in smoking-attributable
      mortality in Poland by selected environmental characteristics. MATERIAL AND
      METHODS: On the basis of the simplified Peto method, standardized smoking
      attributable death rates were estimated by applying data on overall mortality and
      mortality due to malignant neoplasms of trachea, bronchus and lung for the years
      2006-2010 obtained from the Central Statistical Office. The correlation between
      smoking-attributable mortality (SAM) and selected regional characteristics was
      estimated in two models of linear regression (for men and women). The
      characteristics of 379 NUTS-4 regions for the years 2006-2010 were derived from
      the CSO and other public data sources. RESULTS: In both absolute and relative
      terms, the male and female SAM appeared to be higher in the northern and western
      regions of Poland. For both men and women, the linear regression confirmed the
      significant positive correlation between the level of SAM and poverty, hazardous
      working conditions, crime level, low level of settlement, low proportion of
      persons in agriculture and of University graduates. Additional variables
      correlating with the male SAM pointed to unemployment, proportion employed in
      services, mortality due to intentional self-harm and electoral turnout.
      CONCLUSION: At the NUTS-4 level, the territorial variation in male and female SAM
      can be partially explained by the variation in regional characteristics
      indicating unfavourable economic and social conditions.

PMID- 25862454
TI  - Methods of mosquito plague control in Swinoujscie area based on the analysis of
      species distribution.
AB  - OBJECTIVE: Studies conducted in 2013 in Swinoujscie area aimed at determining
      mosquito species distribution and analyzing sites, productivity and dynamics of
      larva and adult breeding as well as developing guidelines for effective mosquito
      control in this area. MATERIALAND METHODS: Entomological studies were conducted
      from March to September 2013. Distribution of mosquito larvae and adults was
      investigated. Mosquito larvae were observed mainly in April in transient snow
      melt pools. RESULTS: Ochlerotatus cantans, Oc. communis, Oc. annulipes, Oc.
      punctor were the most predominant mosquito species. Since July, larvae of the
      following genera: Culex spp., Culiseta spp., Anopheles spp. were collected in
      standing water bodies. A total of 17 species adult mosquito were identified. Of
      them, Oc. communis, Aedes vexans, Culex pipiens/torrentium, Oc. Cantans, Oc.
      caspius predominated over other species. CONCLUSIONS: Mosquito plague in
      Swinoujscie area can be controlled if constant actions would be undertaken from
      April (use of microbial biocides for snow-melt mosquito larva control) to August
      (use of microbial biocides for polygeneration larva species control and use of
      chemical biocides for adult mosquito control). Furthermore, there is a need for
      actions that would make environment less friendly to mosquitoes and would help to
      identify breeding sites of aggressive mosquito species - Aedes vexans. There is
      also a necessity to educate the inhabitants of Swinoujscie area on the danger
      resulting from uncontrolled use of insecticides in protected areas and those
      which are unique from a faunistic perspective.

PMID- 25862455
TI  - Role of perfusion SPECT in prediction and measurement of pulmonary complications
      after radiotherapy for lung cancer.
AB  - PURPOSE: The purpose of the study was to evaluate the ability of baseline
      perfusion defect score (DS) on SPECT to predict the development of severe
      symptomatic radiation pneumonitis (RP) and to evaluate changes in perfusion on
      SPECT as a method of lung perfusion function assessment after curative
      radiotherapy (RT) for non-small-cell lung cancer (NSCLC). METHODS: Patients with
      NSCLC undergoing curative RT were included prospectively. Perfusion SPECT/CT and
      global pulmonary function tests (PFT) were performed before RT and four times
      during follow-up. Functional activity on SPECT was measured using a
      semiquantitative perfusion DS. Pulmonary morbidity was graded by the National
      Cancer Institute's Common Terminology Criteria for Adverse Events version 4 for
      pneumonitis. Patients were divided into two groups according to the severity of
      RP. RESULTS: A total of 71 consecutive patients were included in the study.
      Baseline DS was associated with chronic obstructive pulmonary disease. A
      significant inverse correlation was found between baseline DS and forced
      expiratory volume in 1 s and diffusing capacity of the lung for carbon monoxide.
      Patients with severe RP had significantly higher baseline total lung DS (mean
      5.43) than those with no or mild symptoms (mean DS 3.96, p < 0.01). PFT results
      were not different between these two groups. The odds ratio for total lung DS was
      7.8 (95% CI 1.9 - 31) demonstrating the ability of this parameter to predict
      severe RP. Adjustment for other potential confounders known to be associated with
      increased risk of RP was performed and did not change the odds ratio. The median
      follow-up time after RT was 8.4 months. The largest DS increase of 13.3% was
      associated with severe RP at 3 months of follow-up (p < 0.01). The development of
      severe RP during follow-up was not associated with changes in PFT results.
      CONCLUSION: Perfusion SPECT is a valuable method for predicting severe RP and for
      assessing changes in regional functional perfusion after curative RT comparable
      with global PFT.

PMID- 25862456
TI  - Biphenyl 4-Hydroxylases Involved in Aucuparin Biosynthesis in Rowan and Apple Are
      Cytochrome P450 736A Proteins.
AB  - Upon pathogen attack, fruit trees such as apple (Malus spp.) and pear (Pyrus
      spp.) accumulate biphenyl and dibenzofuran phytoalexins, with aucuparin as a
      major biphenyl compound. 4-Hydroxylation of the biphenyl scaffold, formed by
      biphenyl synthase (BIS), is catalyzed by a cytochrome P450 (CYP). The biphenyl 4
      hydroxylase (B4H) coding sequence of rowan (Sorbus aucuparia) was isolated and
      functionally expressed in yeast (Saccharomyces cerevisiae). SaB4H was named
      CYP736A107. No catalytic function of CYP736 was known previously. SaB4H exhibited
      absolute specificity for 3-hydroxy-5-methoxybiphenyl. In rowan cell cultures
      treated with elicitor from the scab fungus, transient increases in the SaB4H,
      SaBIS, and phenylalanine ammonia lyase transcript levels preceded phytoalexin
      accumulation. Transient expression of a carboxyl-terminal reporter gene construct
      directed SaB4H to the endoplasmic reticulum. A construct lacking the amino
      terminal leader and transmembrane domain caused cytoplasmic localization.
      Functional B4H coding sequences were also isolated from two apple (Malus *
      domestica) cultivars. The MdB4Hs were named CYP736A163. When stems of cv Golden
      Delicious were infected with the fire blight bacterium, highest MdB4H transcript
      levels were observed in the transition zone. In a phylogenetic tree, the three
      B4Hs were closest to coniferaldehyde 5-hydroxylases involved in lignin
      biosynthesis, suggesting a common ancestor. Coniferaldehyde and related compounds
      were not converted by SaB4H. 

PMID- 25862457
TI  - INTERMEDIATE CLEAVAGE PEPTIDASE55 Modifies Enzyme Amino Termini and Alters
      Protein Stability in Arabidopsis Mitochondria.
AB  - Precursor proteins containing mitochondrial peptide signals are cleaved after
      import by a mitochondrial processing peptidase. In yeast (Saccharomyces
      cerevisiae) and human (Homo sapiens), intermediate cleavage peptidase55 (ICP55)
      plays a role in stabilizing mitochondrial proteins by the removal of single amino
      acids from mitochondrial processing peptidase-processed proteins. We have
      investigated the role of a metallopeptidase (At1g09300) from Arabidopsis
      (Arabidopsis thaliana) that has sequence similarity to yeast ICP55. We identified
      this protein in mitochondria by mass spectrometry and have studied its function
      in a transfer DNA insertion line (icp55). Monitoring of amino-terminal peptides
      showed that Arabidopsis ICP55 was responsible for the removal of single amino
      acids, and its action explained the -3 arginine processing motif of a number of
      mitochondrial proteins. ICP55 also removed single amino acids from mitochondrial
      proteins known to be cleaved at nonconserved arginine sites, a subset of
      mitochondrial proteins specific to plants. Faster mitochondrial protein
      degradation rates not only for ICP55 cleaved protein but also for some non-ICP55
      cleaved proteins were observed in Arabidopsis mitochondrial samples isolated from
      icp55 than from the wild type, indicating that a complicated protease degradation
      network has been affected. The lower protein stability of isolated mitochondria
      and the lack of processing of target proteins in icp55 were complemented by
      transformation with the full-length ICP55. Analysis of in vitro degradation rates
      and protein turnover rates in vivo of specific proteins indicated that serine
      hydroxymethyltransferase was affected in icp55. The maturation of serine
      hydroxymethyltransferase by ICP55 is unusual, as it involves breaking an amino
      terminal diserine that is not known as an ICP55 substrate in other organisms and
      that is typically considered a sequence that stabilizes rather than destabilizes
      a protein.

PMID- 25862459
TI  - HMGB1 binding to receptor for advanced glycation end products enhances
      inflammatory responses of human bronchial epithelial cells by activating p38 MAPK
      and ERK1/2.
AB  - The proinflammatory factor high mobility group box protein 1 (HMGB1) has been
      implicated as an important mediator of many chronic inflammatory diseases,
      including asthma. Human bronchial epithelial cells (HBECs) play a central role in
      the pathogenesis of asthma. However, the effects of HMGB1 on HBECs and the
      underlying mechanisms remain unknown. Here, we investigated receptor expression
      and proinflammatory cytokine production by primary cultures of HBECs stimulated
      by HMGB1. We then examined the effects of specific receptor blockade and
      inhibition of p38 MAPK, ERK1/2, or PI3-K on HMGB1-induced expression of
      proinflammatory cytokines. HMGB1 increased the expression and secretion of TNF
      alpha, TSLP, MMP-9, and VEGF in a dose- and time-dependent manner. HMGB1 also
      induced elevated expression of RAGE protein. Secretion of TNF-alpha, VEGF, MMP-9,
      and TSLP was significantly decreased by RAGE blockade and p38 MAPK pathway
      inhibition, while a less pronounced effect was mediated by ERK1/2 inhibition.
      These observations suggest that HMGB1 binds RAGE and promotes activities of p38
      MAPK and ERK1/2 pathways in HBECs. This then enhances the expression of TNF
      alpha, VEGF, MMP-9, and TSLP, which are the important inflammatory factors in
      asthma. These results demonstrate that HMGB1 enhances the inflammatory responses
      of HBECs, which are involved in the modulation of inflammatory processes in
      asthma.

PMID- 25862458
TI  - Eaten alive: novel insights into autophagy from multicellular model systems.
AB  - Autophagy delivers cytoplasmic material to lysosomes for degradation. First
      identified in yeast, the core genes that control this process are conserved in
      higher organisms. Studies of mammalian cell cultures have expanded our
      understanding of the core autophagy pathway, but cannot reveal the unique animal
      specific mechanisms for the regulation and function of autophagy. Multicellular
      organisms have different types of cells that possess distinct composition,
      morphology, and organization of intracellular organelles. In addition, the
      autophagic machinery integrates signals from other cells and environmental
      conditions to maintain cell, tissue and organism homeostasis. Here, we highlight
      how studies of autophagy in flies and worms have identified novel core autophagy
      genes and mechanisms, and provided insight into the context-specific regulation
      and function of autophagy. 

PMID- 25862460
TI  - MiR-492 is functionally involved in Oxaliplatin resistance in colon cancer cells
      LS174T via its regulating the expression of CD147.
AB  - Chemotherapy remains the core of anticancer treatment. However, despite the
      tremendous strides made in the development of targeted anticancer therapies,
      emergence of resistance to chemotherapeutic drugs is still a major obstacle in
      the successful management of resistant tumors. Therefore, profound investigation
      into the in-depth molecular mechanisms of drug resistance is essential and may
      hopefully translate into effective therapies that can flip the switch from drug
      resistance to susceptibility. To develop novel-targeted therapy holds promise for
      conquering chemotherapy resistance, one of the major hurdles in current colon
      cancer treatment. Previous studies indicate that CD147 is involved in the
      progression of chemotherapy resistance in breast cancer and ovarian cancer cells
      and its expression is negative regulated by miR-492 in muscles cells. In the
      present study, we found that lower level of miR-492 is accompanied with increased
      expression of CD147 in Oxaliplatin-resistant colon cancer cell line LS174T/L-OHP
      as compared with its parental cell line LS174T. Exogenous expression of miR-492
      in LS174T/L-OHP could sensitize its reaction on the treatment of Oxaliplatin,
      which is coincided with its directly reducing the expression of CD147.
      Furthermore, we found that knockdown of CD147 in LS174T/L-OHP could also
      sensitize its reaction of the treatment with Oxaliplatin. Besides, intratumoral
      delivering of miR-492 could also restore Oxaliplatin treatment response in
      Oxaliplatin-resistant xenografts in vivo. These findings provide direct evidences
      that the miR-492/CD147 axis might play an essential role in the Oxaliplatin
      resistance of colon cancer cells, suggesting that the miR-492/CD147 signaling
      cohort could be served as a novel therapeutic target for the treatment of
      chemotherapy resistant in colon cancer. 

PMID- 25862461
TI  - Association of glycaemia with perceived threat of illness in patients with type 2
      diabetes.
AB  - BACKGROUND: It is essential to reach glycaemic control in patients with diabetes
      mellitus to prevent reduced life expectancy and morbidity related to
      complications. The aim of this study was to determine whether glycaemic control
      is associated with the perception of illness in type II diabetes mellitus.
      METHODOLOGY: Illness perception was assessed in a sample of 242 diabetics
      attending a Family Health Centre in Chile using the Brief Illness Perception
      Questionnaire (BIPQ). We considered well-controlled individuals to have glycated
      haemoglobin below 7%, and we assessed association with the BIPQ score. The data
      were analysed by logistic regression. RESULTS: The total BIPQ score was
      significantly higher (more negative perception) in non-controlled individuals;
      the most significant differences were found in the following dimensions:
      consequences (p=0.0003), personal control (p=0.0392), identity (p=0.0006) and
      emotional affection (p=0.018). The dimensions of timeline, treatment control,
      concern and coherence showed no differences between the groups. The mean age of
      well-controlled subjects was significantly higher than the age of non-controlled
      diabetics. Well-controlled patients had been diagnosed with diabetes for
      significantly fewer years than had those that were not. CONCLUSIONS: Perceiving
      illness as more negative (BIPQ score >37) is highly associated with being a non
      controlled diabetic, with more consequences over their daily life, less control
      over the disease and a higher number of attributable symptoms. When control
      variables are considered, a negative perception of diabetes has an adjusted OR of
      2.14 (CI 95% 1.17-3.92) to have glycated haemoglobin above 7%.

PMID- 25862462
TI  - Developing Enhanced Blood-Brain Barrier Permeability Models: Integrating External
      Bio-Assay Data in QSAR Modeling.
AB  - PURPOSE: Experimental Blood-Brain Barrier (BBB) permeability models for drug
      molecules are expensive and time-consuming. As alternative methods, several
      traditional Quantitative Structure-Activity Relationship (QSAR) models have been
      developed previously. In this study, we aimed to improve the predictivity of
      traditional QSAR BBB permeability models by employing relevant public bio-assay
      data in the modeling process. METHODS: We compiled a BBB permeability database
      consisting of 439 unique compounds from various resources. The database was split
      into a modeling set of 341 compounds and a validation set of 98 compounds.
      Consensus QSAR modeling workflow was employed on the modeling set to develop
      various QSAR models. A five-fold cross-validation approach was used to validate
      the developed models, and the resulting models were used to predict the external
      validation set compounds. Furthermore, we used previously published membrane
      transporter models to generate relevant transporter profiles for target
      compounds. The transporter profiles were used as additional biological
      descriptors to develop hybrid QSAR BBB models. RESULTS: The consensus QSAR models
      have R(2) = 0.638 for five-fold cross-validation and R(2) = 0.504 for external
      validation. The consensus model developed by pooling chemical and transporter
      descriptors showed better predictivity (R(2) = 0.646 for five-fold cross
      validation and R(2) = 0.526 for external validation). Moreover, several external
      bio-assays that correlate with BBB permeability were identified using our
      automatic profiling tool. CONCLUSIONS: The BBB permeability models developed in
      this study can be useful for early evaluation of new compounds (e.g., new drug
      candidates). The combination of chemical and biological descriptors shows a
      promising direction to improve the current traditional QSAR models.

PMID- 25862463
TI  - Urea enhances the photodynamic efficiency of methylene blue.
AB  - Methylene blue (MB) is a well-known photosensitizer used mostly for antimicrobial
      photodynamic therapy (APDT). MB tends to aggregate, interfering negatively with
      its singlet oxygen generation, because MB aggregates lean towards electron
      transfer reactions, instead of energy transfer with oxygen. In order to avoid MB
      aggregation we tested the effect of urea, which destabilizes solute-solute
      interactions. The antimicrobial efficiency of MB (30 MUM) either in water or in
      2M aqueous urea solution was tested against a fungus (Candida albicans). Samples
      were kept in the dark and irradiation was performed with a light emitting diode
      (lambda = 645 nm). Without urea, 9 min of irradiation was needed to achieve
      complete microbial eradication. In urea solution, complete eradication was
      obtained with 6 min illumination (light energy of 14.4 J). The higher efficiency
      of MB/urea solution was correlated with a smaller concentration of dimers, even
      in the presence of the microorganisms. Monomer to dimer concentration ratios were
      extracted from the absorption spectra of MB solutions measured as a function of
      MB concentration at different temperatures and at different concentrations of
      sodium chloride and urea. Dimerization equilibrium decreased by 3 and 6 times in
      1 and 2M urea, respectively, and increased by a factor of 6 in 1M sodium
      chloride. The destabilization of aggregates by urea seems to be applied to other
      photosensitizers, since urea also destabilized aggregation of Meso-tetra(4-n
      methyl-pyridyl)porphyrin, which is a positively charged porphyrin. We showed that
      urea destabilizes MB aggregates mainly by causing a decrease in the enthalpic
      gain of dimerization, which was exactly the opposite of the effect of sodium
      chloride. In order to understand this phenomenon at the molecular level, we
      computed the free energy for the dimer association process (DeltaG(dimer)) in
      aqueous solution as well as its enthalpic component in aqueous and in
      aqueous/urea solutions by molecular dynamics simulations. In 2M-urea solution the
      atomistic picture revealed a preferential solvation of MB by urea compared with
      MB dimers while changes in DeltaH(dimer) values demonstrated a clear shift
      favoring MB monomers. Therefore, MB monomers are more stable in urea solutions,
      which have significantly better photophysics and higher antimicrobial activity.
      This information can be of use for dental and medical professionals that are
      using MB based APDT protocols.

PMID- 25862464
TI  - Choice of Outcome Measure in an Economic Evaluation: A Potential Role for the
      Capability Approach.
AB  - The last decade has seen a renewed interest in Sen's capability approach; health
      economists have been instrumental in leading much of this work. One particular
      stream of research is the application of the approach to outcome measurement. To
      date, there have been a dozen attempts (some combined) to operationalise the
      approach, and produce an outcome measure that offers a broader evaluative space
      than health-related quality-of-life measures. Applications have so far been
      confined to public health, physical, mental health and social care interventions,
      but the capability approach could be of benefit to evaluations of
      pharmacotherapies and other technologies. This paper provides an introduction to
      the capability approach, reviews the measures that are available for use in an
      economic evaluation, including their current applications, and then concludes
      with a discussion of a number of issues that require further consideration before
      the approach is adopted more widely to inform resource allocation decisions.

PMID- 25862465
TI  - Clonal Dissemination of a Single Vibrio cholerae O1 Biotype El Tor Strain in
      Sistan-Baluchestan Province of Iran During 2013.
AB  - Although much is known about the mechanisms affecting cholera spread, cholera
      outbreaks occur annually in Iran. The aim of this study was to characterize and
      assess the clonal correlation of strains obtained from an outbreak in 2013 in
      Iran. Thirty-three strains of Vibrio cholerae were isolated from stool sample of
      patients majority of them belonged to Afghan nationality. PCR and sequencing
      analysis was performed to characterize virulence and resistance associates genes
      and cassettes. Clonality of isolates was assessed by Pulsed-field gel
      electrophoresis (PFGE) method. The ctx, zot, and tcp genes were present in 100 %
      of isolates. The wbeT gene was absent in all V. cholerae outbreak isolates,
      integrity of which is essential for Ogawa phenotype. This correlates with Inaba
      phenotype of all isolates under study. Sequencing of the ctxB (+) strains
      revealed that all isolates (El Tor strains) possessed the ctxB sequence of
      classical biotype allele known as El Tor variant strains. No class 1 or 2
      integrons were detected among the isolates which indicate that in spite of high
      rate of resistance, integrons do not play an important role in V. cholerae
      resistance. All isolates were chloramphenicol sensitive all of which showed
      resistance to tetracycline and harbored the tetB resistance gene. PFGE analysis
      showed identical pulsotypes indicative of clonal dissemination of a single V.
      cholerae strain among the patients under study. Clonal cholera outbreak in
      boarder cities is alarming due to fear of import and spread of V. cholerae
      strains from out of the country which may lead to more spreading epidemics. 

PMID- 25862467
TI  - Childhood epilepsy with centrotemporal spikes: Perhaps not so benign after all.

PMID- 25862466
TI  - The Antibacterial Effects of an Antimicrobial Peptide Human beta-Defensin 3 Fused
      with Carbohydrate-Binding Domain on Pseudomonas aeruginosa PA14.
AB  - Pseudomonas aeruginosa is one of the most opportunistic bacterial pathogens in
      human communities. Being a potential antibacterial agent, antimicrobial peptide
      human beta-defensin 3-carbohydrate-binding domain (hBD3-CBD) was evaluated in
      this study by in vitro bactericidal test, special gene expressions, hBD3-CBD
      effects on biofilm formation assays, swimming, twitching, and swarming activities
      of P. aeruginosa PA14, and hBD3-CBD effects on the antibiotic 50 % minimal
      inhibitory concentration (MIC50) and 90 % minimal inhibitory concentration
      (MIC90) against clinical P. aeruginosa isolates. The MIC against P. aeruginosa
      PA14 was 32 MUg/ml; hBD3-CBD showed significant bactericidal activities when the
      concentration reached 8 MUg/ml, and when the concentration reached 2 MUg/ml, hBD3
      CBD successfully repressed the biofilm productions in P. aeruginosa PA14. hBD3
      CBD could inhibit the in vitro swimming, twitching, and swarming activities of P.
      aeruginosa PA14. When 5 MUg/ml hBD3-CBD was combined with antibiotics, it
      decreased the MIC50 and MIC90 of tetracycline, rifampicin, and streptomycin
      against clinical P. aeruginosa isolates. As new antibacterial agents, hBD3-CBD
      and other AMPs might be used together with antibiotics to deal with infections in
      the future, especially the skin and soft tissue infections of drug-resistant P.
      aeruginosa. 

PMID- 25862468
TI  - Shared decision-making in epilepsy management.
AB  - Policy makers, clinicians, and patients increasingly recognize the need for
      greater patient involvement in clinical decision-making. Shared decision-making
      helps address these concerns by providing a framework for clinicians and patients
      to make decisions together using the best evidence. Shared decision-making is
      applicable to situations where several acceptable options exist (clinical
      equipoise). Such situations occur commonly in epilepsy, for example, in decisions
      regarding the choice of medication, treatment in pregnancy, and medication
      withdrawal. A talk model is a way of implementing shared decision-making during
      consultations, and decision aids are useful tools to assist in the process.
      Although there is limited evidence available for shared decision-making in
      epilepsy, there are several benefits of shared decision-making in general
      including improved decision quality, more informed choices, and better treatment
      concordance. 

PMID- 25862469
TI  - Validation of the Neuro-QoL measurement system in children with epilepsy.
AB  - OBJECTIVE: Children with epilepsy often face complex psychosocial consequences
      that are not fully captured by existing patient-reported outcome (PRO) measures.
      The Neurology Quality of Life Measurement System "Neuro-QoL" was developed to
      provide a set of common PRO measures that address issues important to people with
      neurologic disorders. This paper reports Neuro-QoL (anxiety, depression,
      interaction with peers, fatigue, pain, cognitive function, stigma, and upper and
      lower extremity functions) validation in children with epilepsy. METHOD: Patients
      (aged 10-18years) diagnosed with epilepsy completed Neuro-QoL and legacy measures
      at time 1 (initial study visit) and 6-month follow-up. Internal consistency
      reliability was also evaluated. Concurrent validity was assessed by comparing
      Neuro-QoL measures with more established "legacy" measures of the same concepts.
      Clinical validity was evaluated by comparing mean Neuro-QoL scores of patients
      grouped by clinical anchors such as disease severity. Responsiveness of the Neuro
      QoL from time 1 (initial study visit) to 6months was evaluated using self
      reported change as the primary anchor. RESULTS: Sixty-one patients (mean
      age=13.4years; 62.3% male, 75.9% white) participated. Most patients (64.2%) had
      been seizure-free in the 3months prior to participation, and seizure frequency
      was otherwise described as follows: 17.8% daily, 13.3% weekly, 35.6% monthly, and
      33.3% yearly. All patients were taking antiepileptic drugs. Patients reported
      better function/less symptoms compared to the reference groups. Internal
      consistency (alpha) coefficients ranged from 0.76 to 0.87. Patients with
      different seizure frequencies differed on anxiety (p<.01) and cognitive function
      (p<.05). Compared to patients on polytherapy, those on monotherapy had better
      upper extremity scores (p<.05). Compared to those with localized seizures, those
      experiencing generalized seizures reported worse stigma (p<.05). Depression,
      anxiety, lower extremity, fatigue, pain, interaction with peers, and stigma also
      significantly discriminated patients with different levels of quality of life
      (p<=.05). All Neuro-QoL measures were significantly correlated with other
      measures assessing similar domains. Stigma was related to self-reported change in
      several areas of functioning but in sometimes unexpected directions.
      SIGNIFICANCE: The Neurology Quality of Life Measurement System is a valid and
      reliable assessment tool for children with epilepsy and can be used in research
      and clinical settings.

PMID- 25862470
TI  - Minding the gap: Interprofessional communication during inpatient and post
      discharge chasm care.
AB  - OBJECTIVE: Poor communication is cited as a main cause of poor patient outcomes
      and errors in healthcare, and clear communication can be especially critical
      during transitions such as discharge. In this project, communication was
      standardized for clarity, and techniques were implemented to continue care from
      inpatient, to discharge, across the post-discharge chasm, to hand-off with the
      primary care provider (PCP). METHODS: The interprofessional (IP) quality
      improvement initiative included: (1) evidence-based teamwork system; (2) in situ
      simulation; (3) creation of an IP model of care; and (4) innovations in use of
      telehealth technology to continue care post-discharge. RESULTS: Measures
      inpatient/parent satisfaction and the attitudes of the care team have improved.
      CONCLUSIONS: Traditional methods of communication and transition do not meet
      patient or healthcare provider needs. Communication must be standardized to be
      understandable and be used by the IP team. Care must continue post-discharge by
      utilizing technology to increase quality and continuity of care. PRACTICE
      IMPLICATIONS: Improving and practicing communication skills may lead to
      reductions in healthcare errors and readmissions, and may decrease the length of
      stay and improve satisfaction of care teams.

PMID- 25862471
TI  - Potentials and capabilities of the Extracellular Vesicle (EV) Array.
AB  - Extracellular vesicles (EVs) and exosomes are difficult to enrich or purify from
      biofluids, hence quantification and phenotyping of these are tedious and
      inaccurate. The multiplexed, highly sensitive and high-throughput platform of the
      EV Array presented by Jorgensen et al., (J Extracell Vesicles, 2013; 2: 10) has
      been refined regarding the capabilities of the method for characterization and
      molecular profiling of EV surface markers. Here, we present an extended
      microarray platform to detect and phenotype plasma-derived EVs (optimized for
      exosomes) for up to 60 antigens without any enrichment or purification prior to
      analysis. 

PMID- 25862472
TI  - Spike history neural response model.
AB  - There is a potential for improved efficacy of neural stimulation if stimulation
      levels can be modified dynamically based on the responses of neural tissue in
      real time. A neural model is developed that describes the response of neurons to
      electrical stimulation and that is suitable for feedback control neuroprosthetic
      stimulation. Experimental data from NZ white rabbit retinae is used with a data
      driven technique to model neural dynamics. The linear-nonlinear approach is
      adapted to incorporate spike history and to predict the neural response of
      ganglion cells to electrical stimulation. To validate the fitness of the model,
      the penalty term is calculated based on the time difference between each
      simulated spike and the closest spike in time in the experimentally recorded
      train. The proposed model is able to robustly predict experimentally observed
      spike trains. 

PMID- 25862473
TI  - Wide-range screening of psychoactive substances by FIA-HRMS: identification
      strategies.
AB  - Recreational drugs (illicit drugs, human and veterinary medicines, legal highs,
      etc.) often contain lacing agents and adulterants which are not related to the
      main active ingredient. Serious side effects and even the death of the consumer
      have been related to the consumption of mixtures of psychoactive substances
      and/or adulterants, so it is important to know the actual composition of
      recreational drugs. In this work, a method based on flow injection analysis (FIA)
      coupled with high-resolution mass spectrometry (HRMS) is proposed for the fast
      identification of psychoactive substances in recreational drugs and legal highs.
      The FIA and HRMS working conditions were optimized in order to detect a wide
      range of psychoactive compounds. As most of the psychoactive substances are acid
      base compounds, methanol-0.1 % aqueous formic acid (1:1 v/v) as a carrier solvent
      and electrospray in both positive ion mode and negative ion mode were used. Two
      data acquisition modes, full scan at high mass resolution (HRMS) and data
      dependent tandem mass spectrometry (ddMS/HRMS) with a quadrupole-Orbitrap mass
      analyzer were used, resulting in sufficient selectivity for identification of the
      components of the samples. A custom-made database containing over 450 substances,
      including psychoactive compounds and common adulterants, was built to perform a
      high-throughput target and suspect screening. Moreover, online accurate mass
      databases and mass fragmenter software were used to identify unknowns. Some
      examples, selected among the analyzed samples of recreational drugs and legal
      highs using the FIA-HRMS(ddMS/HRMS) method developed, are discussed to illustrate
      the screening strategy used in this study. The results showed that many of the
      analyzed samples were adulterated, and in some cases the sample composition did
      not match that of the supposed marketed substance. 

PMID- 25862474
TI  - Quantification of 3-MCPD and its mercapturic metabolite in human urine:
      validation of an LC-MS-MS method and its application in the general population.
AB  - A new method for the simultaneous quantitative determination in human urine of 3
      monochloropropane-1,2-diol (3-MCPD), a toxic food contaminant, and its
      metabolite, 2,3-dihydroxypropyl mercapturic acid (DHPMA), was developed and
      validated. After urine dilution, the analytes were separated on an
      Atlantis(r)dC18 column and quantified by liquid chromatography-tandem mass
      spectrometry using isotopically labelled internal standards. The limits of
      quantification (S/N = 10) were 1.90 and 2.21 MUg/L for 3-MCPD and DHPMA,
      respectively. Intra- and inter-day precision were lower than 6 % for each
      compound. Matrix effects were evaluated. Due to the high sensitivity and good
      accuracy of the method, 3-MCPD and DHPMA were found in 67 and 100 % of urine
      samples of healthy subjects, respectively. 

PMID- 25862475
TI  - Fortified versus incurred residues: extraction of furazolidinone metabolite from
      prawn.
AB  - Most methods reported in the literature for determination of nitrofuran
      metabolites use the same extraction and derivatisation conditions to hydrolyse
      and extract the protein-bound residues from animal tissue. While undertaking
      certification of reference materials for nitrofuran metabolites in freeze-dried
      prawn, it was found that these conditions are satisfactory for recovery of spiked
      residues; however, extraction efficiencies of incurred furazolidinone could be
      substantially increased by further optimisation of the extraction conditions. The
      availability of a suitable certified reference material allows laboratories to
      ensure that their method is optimised for incurred residues. 

PMID- 25862477
TI  - Realising the promise of non-invasive prenatal testing.

PMID- 25862476
TI  - Phototherapy improves wound healing in rats subjected to high-fat diet.
AB  - This study aimed to compare the phototherapy effects on wound healing in rats
      submitted to normal and high-fat diets. Thirty-six rats received normal lipidic
      diet (NL) and 36 high lipidic (HL) diet for 45 days. The nutritional status was
      measured by body mass, blood glucose, total cholesterol, and triglycerides
      levels. Four experimental groups were performed according light (L) therapy
      applied "on" or "off" (660 nm, 100 mW, 70 J/cm(2), 2 J) on 1.5-mm-punched dorsum
      skin wounds as NLL+, NLL-, HLL+, and HLL-. The wound healing rate (WHR) and
      oxidative stress markers were analyzed on 2nd, 7th, and 14th days. Despite no
      difference among body mass, the HL rats presented higher blood glucose, total
      cholesterol, and triglycerides levels than NL rats. Respectively, on the 2nd and
      14th days, the HLL+ group presented the highest WHRs (0.38 +/- 0.16/0.97 +/-
      0.02) among all groups, while the HLL- (-0.002 +/- 0.12/0.81 +/- 12.1) the lowest
      WHRs. Hydroxyproline level was lower in HLL- (6.41 +/- 1.09 MUg/mg) than HLL+
      (7.71 +/- 0.61 MUg/mg) and also NLL+ (9.33 +/- 0.84 MUg/mg). HLL+ presented
      oxidative stress markers similar to normal control group (NLL-) during follow up
      and highest antioxidant defense on 7th day. The results showed phototherapy
      accelerated the cutaneous wound healing by modulating oxidative stress in rats
      with metabolic disorders under a high-fat diet. 

PMID- 25862478
TI  - World Molecular Imaging Congress 2015: precision medicine visualized.

PMID- 25862479
TI  - Selenite activates the ATM kinase-dependent DNA repair pathway in human
      osteosarcoma cells with mitochondrial dysfunction.
AB  - Mitochondrial dysfunction and reactive oxygen species (ROS) induced oxidative
      damage are implicated in the pathogenesis of several human diseases. Based on our
      previous findings that ROS level was higher in human osteosarcoma cybrids-
      Neuropathy, Ataxia and Retinitis Pigmentosa (NARP) and was reduced by selenite
      treatment, this study was designed to elucidate the effects of selenite
      administration on oxidative and nitrosative damage to lipids, proteins and DNA.
      Oxidative and nitrosative damage to lipids and proteins was not increased in NARP
      cybrids or mitochondrial DNA-lacking Rho0 cells (displaying mitochondrial
      dysfunction) when compared with control WT cells. However, we found the enhanced
      formation of DNA double-strand breaks based on the level of histone gammaH2AX
      (phosphorylated at Ser 139), which is known to be phosphorylated by ATM (Ataxia
      Telangiectasia Mutated) kinase in response to DNA damage. Selenite increased the
      activity of ATM kinase in NARP cybrids and Rho0 cells without concomitant
      increase in levels of histone gammaH2AX. Activation of the ATM kinase-dependent
      DNA repair pathway triggered by selenite could not be associated with enhanced
      DNA damage but might rather result from selenite-induced activation of ATM
      dependent DNA repair mechanisms which could account for protective effects of
      this agent.

PMID- 25862480
TI  - Environmental Surveillance of Non-polio Enteroviruses in Poland, 2011.
AB  - The aim of this study was to apply environmental surveillance to evaluate
      circulation of non-polio enteroviruses (NPEVs) in sewage in Poland. Samples of
      raw sewage were collected in 14 sewage disposal systems from January to December,
      2011. Sewage samples were concentrated prior to analysis by RT-PCR and isolation
      in cells (RD, L20B and Caco-2). Out of the 165 analysed samples, 127 (77%) were
      positive for enteroviruses using RT-PCR and 109 (66%) were positive for
      enteroviruses using cell culture methods and the highest detection rate was
      observed in the summer and autumn. In total, 141 enteroviruses were identified
      using neutralization test (107 NPEVs and 34 polioviruses). Accounting for 52% of
      all the detected NPEVs, E11 and E3 were the predominant serotypes identified in
      raw sewage. Retrospectively, E11 was the known aetiology for the past aseptic
      meningitis outbreaks in Poland, as E3 being rarely associated with any outbreak
      prior to 2013. In conclusion, the environmental surveillance provides data which
      may help in understanding the epidemiology of enteroviruses in humans.

PMID- 25862481
TI  - Identification of cortical lesions using DIR and FLAIR in early stages of
      multiple sclerosis.
AB  - The use of non-routine MRI sequences such as DIR has highlighted the role of gray
      matter (GM) pathology in multiple sclerosis (MS). The aim of this study was to
      assess the detection and relevance of cortical lesions (CLs) using MRI in early
      (<5 years) MS patients. 3D DIR and 3D FLAIR images at 3T from 122 patients [93
      relapsing-remitting MS (RRMS), 29 clinically isolated syndrome (CIS)] were scored
      for CLs by two blinded readers. Patients were divided into two groups depending
      on the presence or absence of CLs. For FLAIR, 51 CLs were identified, of which 13
      were purely intracortical and 38 mixed CLs; for DIR, this was 60 in total and 16
      and 44, respectively. In both groups, there was no difference in GM fraction.
      Neuropsychological testing was performed for a subgroup of 66 patients. In 22.1 %
      of patients CLs were identified. The number of CLs revealed an association with
      lower working memory scores and semantical word fluency. Overall, CLs imaged with
      3D FLAIR and 3D DIR sequences are found more frequently in RRMS patients than CIS
      and may also be a correlate for mild neuropsychological pathology.

PMID- 25862482
TI  - Genetic landscape remodelling in spinocerebellar ataxias: the influence of next
      generation sequencing.
AB  - Hereditary cerebellar ataxias (HCAs) are clinically and genetically heterogeneous
      neurodegenerative disorders, characterised by a cerebellar syndrome and other
      neurological or non-neurological signs. So far, more than 20 genes have been
      described in autosomal dominant HCA; in autosomal recessive HCA, even more genes
      are involved, in often more complex phenotypes. Because of that complexity, the
      genetic diagnosis of these diseases is often based on the next-generation
      sequencing techniques. In this review paper, we discuss the major contributions
      that they have made to the genetic landscape of HCAs. Numerous novel genes have
      been identified; still more have recently been implicated in HCAs in addition to
      being responsible for other diseases. The phenotypic spectrum associated with a
      single gene constantly gains in complexity. Novel types of mutations or
      transmissions in known genes are regularly being identified. All these factors
      make genotype-phenotype correlations particularly difficult. Some but not all of
      this variability can be explained by different pathophysiological consequences
      (loss of function, gain of function, variable levels of haploinsufficiency). This
      also raises the question of modifier genes. Finally, we highlight some functional
      pathways that increasingly appear important in HCAs.

PMID- 25862483
TI  - Clinical, FDG and amyloid PET imaging in posterior cortical atrophy.
AB  - The purpose of this study was to identify the clinical, [(18)F]
      fluorodeoxyglucose positron emission tomography (FDG-PET) and amyloid-PET
      findings in a large cohort of posterior cortical atrophy (PCA) patients, to
      examine the neural correlates of the classic features of PCA, and to better
      understand the features associated with early PCA. We prospectively recruited 25
      patients who presented to the Mayo Clinic between March 2013 and August 2014 and
      met diagnostic criteria for PCA. All patients underwent a standardized set of
      tests and amyloid imaging with [(11)C] Pittsburg compound B (PiB). Seventeen (68
      %) underwent FDG-PET scanning. We divided the cohort at the median disease
      duration of 4 years in order to assess clinical and FDG-PET correlates of early
      PCA (n = 13). The most common clinical features were simultanagnosia (92 %),
      dysgraphia (68 %), poly-mini-myoclonus (64 %) and oculomotor apraxia (56.5 %). On
      FDG-PET, hypometabolism was observed bilaterally in the lateral and medial
      parietal and occipital lobes. Simultanagnosia was associated with hypometabolism
      in the right occipital lobe and posterior cingulum, optic ataxia with
      hypometabolism in left occipital lobe, and oculomotor apraxia with hypometabolism
      in the left parietal lobe and posterior cingulate gyrus. All 25 PCA patients were
      amyloid positive. Simultanagnosia was the only feature present in 85 % of early
      PCA patients. The syndrome of PCA is associated with posterior hemisphere
      hypometabolism and with amyloid deposition. Many of the classic features of PCA
      show associated focal, but not widespread, areas of involvement of these
      posterior hemispheric regions. Simultanagnosia appears to be the most common and
      hence sensitive feature of early PCA.

PMID- 25862484
TI  - Failure to confirm benefit of acetyl-DL-leucine in degenerative cerebellar
      ataxia: a case series.

PMID- 25862485
TI  - Rethinking disability: the social model of disability and chronic disease.
AB  - Disability is commonly viewed as a problem that exists in a person's body and
      requires medical treatment. The social model of disability, by contrast,
      distinguishes between impairment and disability, identifying the latter as a
      disadvantage that stems from a lack of fit between a body and its social
      environment. This paper describes the social model of disability and then
      considers how it might deal with chronic disease or impairment and why medical
      professionals should learn about disability perspectives to improve their
      practice. 

PMID- 25862486
TI  - A more informed evaluation of medial compartment loading: the combined use of the
      knee adduction and flexor moments.
AB  - OBJECTIVE: To evaluate if the peak knee flexor moment (pKFM) provides unique and
      meaningful information about peak medial compartment loading above and beyond
      what is obtained from the peak knee adduction moment. METHODS: Standard video
      based motion capture and EMG recordings were collected for 10 anterior cruciate
      ligament (ACL) reconstructed subjects walking at a self-selected speed. Knee
      joint moments were obtained using inverse dynamics and medial contact force was
      computed using an EMG-driven musculoskeletal model. Linear regression with the
      peak adductor moment entered first was implemented to isolate the unique
      contribution of the peak flexor moment to peak medial loading. RESULTS: Peak
      moments and medial contact force occurred during weight acceptance at
      approximately 23% of stance. The peak knee adduction moment (pKAM) was a
      significant predictor of peak medial loading (P = 0.004) accounting for
      approximately 63% of the variance. The pKFM was also a significant predictor (P =
      0.009) accounting for an additional 22% of the variance. When entered together
      pKAM and pKFM accounted for more than 85% of the variance in peak medial
      compartment loading. CONCLUSION: The combined use of the peak knee flexor and
      adductor moments provides a significantly more accurate estimate of peak medial
      joint loading than the peak adduction moment alone. More accurate inferences of
      joint contact force will assist clinicians and researchers investigating
      relationships between joint loading and the onset and progression of knee
      osteoarthritis (OA).

PMID- 25862487
TI  - The Budapest Reference Connectome Server v2.0.
AB  - The connectomes of different human brains are pairwise distinct: we cannot talk
      about an abstract "graph of the brain". Two typical connectomes, however, have
      quite a few common graph edges that may describe the same connections between the
      same cortical areas. The Budapest Reference Connectome Server v2.0 generates the
      common edges of the connectomes of 96 distinct cortexes, each with 1015 vertices,
      computed from 96 MRI data sets of the Human Connectome Project. The user may set
      numerous parameters for the identification and filtering of common edges, and the
      graphs are downloadable in both csv and GraphML formats; both formats carry the
      anatomical annotations of the vertices, generated by the FreeSurfer program. The
      resulting consensus graph is also automatically visualized in a 3D rotating brain
      model on the website. The consensus graphs, generated with various parameter
      settings, can be used as reference connectomes based on different, independent
      MRI images, therefore they may serve as reduced-error, low-noise, robust graph
      representations of the human brain. The webserver is available at
      http://connectome.pitgroup.org. 

PMID- 25862488
TI  - Focal adhesion kinase and p53 synergistically decrease neuroblastoma cell
      survival.
AB  - Neuroblastoma is the most common extracranial solid tumor of childhood and is
      responsible for over 15% of pediatric cancer deaths. Focal adhesion kinase (FAK)
      is a nonreceptor tyrosine kinase that is important in many facets of
      neuroblastoma tumor development and progression. The p53 oncogene, although wild
      type in most neuroblastomas, lacks significant function as a tumor suppressor in
      these tumors. Recent reports have found that FAK and p53 interact in some tumor
      types. We have hypothesized FAK and p53 coordinately control each other's
      expression and also interact in neuroblastoma. In the present study, we showed
      that not only do FAK and p53 interact but each one controls the expression of the
      other. In addition, we also examined the effects of FAK inhibition combined with
      p53 activation in neuroblastoma and showed that these two, in combination, had a
      synergistic effect on neuroblastoma cell survival. The findings from this present
      study help to further our understanding of the regulation of neuroblastoma
      tumorigenesis and may provide novel therapeutic strategies and targets for
      neuroblastoma and other pediatric solid tumors. 

PMID- 25862489
TI  - FTY720 mitigates torsion/detorsion-induced testicular injury in rats.
AB  - BACKGROUND: FTY720, a sphingosine-1-phosphate (S1P) receptor agonist, possesses
      potent anti-inflammation capacity. We evaluated the therapeutic potentials of
      FTY720 against testicular injury induced by testicular torsion and/or detorsion
      (T/D). MATERIALS AND METHODS: Young adult male Sprague-Dawley rats were allocated
      to receive T/D (the T/D group) and T/D plus FTY720 (4 mg/kg, the T/D-FTY group, n
      = 6 in each group). To investigate the possible roles of the S1P receptors,
      another group of rats received T/D plus FTY720 plus the potent S1P receptor
      antagonist VPC23019 (1 mg/kg, the T/D-FTY-VPC group, n = 6). FTY720 was
      administered immediately before testicular detorsion, and VPC23019 was
      administered 30 min before FTY720. Another set of rats that received sham
      operation, immediately followed by injection of normal saline, FTY720, or FTY720
      plus VPC23019, served as control groups. Sham control groups were run
      simultaneously. After euthanization, levels of testicular injury were measured.
      RESULTS: Histologic findings revealed severe testicular injury changes in both
      the T/D and T/D-FTY-VPC groups and moderate testicular injury changes in the T/D
      FTY group. In addition, malondialdehyde activity (oxidative status),
      concentration of interleukin-1beta (inflammation index), myeloperoxidase activity
      (neutrophil infiltration index), and wet-to-dry weight ratio (tissue edema index)
      of both the T/D and T/D-FTY-VPC groups were significantly higher than those of
      the T/D-FTY group. These data confirmed the protective effects of FTY720 against
      testicular T/D. Moreover, antagonizing the S1P receptors could reverse the
      protective effects of FTY720. CONCLUSIONS: FTY720 significantly mitigated
      testicular injury induced by testicular T/D. The mechanisms may involve
      activating the S1P receptors.

PMID- 25862490
TI  - Role of the spleen in liver regeneration in relation to transforming growth
      factor-beta1 and hepatocyte growth factor.
AB  - BACKGROUND: Optimizing the hepatic regenerative capacity is an immediate priority
      after partial hepatectomy (PH). Recent reports have indicated improvement in
      liver regeneration after splenectomy, raising interest on the role of the spleen
      in liver regeneration. However, little is known about the exact mechanism
      underlying these effects. MATERIALS AND METHODS: Eight-week-old male Sprague
      Dawley rats randomly underwent either 70% PH only (PH, n = 25) or 70% PH combined
      with splenectomy (PHS, n = 25). The specimens, including liver and/or spleen
      tissues and sera, were collected and evaluated using immunohistochemistry,
      Western blotting, enzyme-linked immunosorbent assay, and serum biochemical
      analyses. RESULTS: PH induced higher transforming growth factor (TGF)-beta1
      expression in the liver up to 72 h after PH. The PHS group showed significantly
      higher numbers of proliferating cell nuclear antigen-positive cells, reflecting
      higher liver regeneration and lower amounts of liver enzymes compared with the PH
      group. Splenectomy after PH resulted in increased and decreased serum
      concentrations of hepatocyte growth factor (HGF) and TGF-beta1 in the portal
      vein, respectively. Moreover, the PHS group demonstrated downregulation of TGF
      beta1 and its receptor TGF-beta-RII and upregulation of HGF and its receptor c
      Met in the liver. CONCLUSIONS: The spleen seemed to exhibit an inhibitory effect
      on liver regeneration by upregulating TGF-beta1 and its receptor TGF-beta-RII and
      downregulating HGF and its receptor c-Met in the liver. Therefore, splenectomy
      can be considered an option for improving liver regeneration in selected patients
      with reduced regenerative capacity of the liver.

PMID- 25862491
TI  - A pelvic floor muscle training program in postmenopausal women: A randomized
      controlled trial.
AB  - OBJECTIVES: The purpose of this study was to investigate if a specific pelvic
      floor muscle training (PFMT) program effectively increases pelvic floor muscle
      (PFM) contractility and decreases anterior pelvic organ prolapse (POP) as well as
      urogynecological symptoms, in postmenopausal women. The mean outcome measure of
      this study was the pelvic floor surface electromyography (sEMG) activity. STUDY
      DESIGN: A clinical, randomized, blinded-assessor and controlled study was
      conducted with 46 postmenopausal women. Thirty women completed this study (mean
      age of 65.93 years), divided into two groups: Treatment Group - TG (n=18) and
      Control Group - CG (n=12). The evaluation was carried out using digital
      palpation, sEMG, pelvic organ prolapse quantification (POP-Q) as well as
      validated questionnaires by the International Consultation on Incontinence
      Questionnaires to investigate urogynecological symptoms. The treatment protocol
      consisted of 12 group sessions, twice a week, with 30 min of duration each. These
      data were then submitted to statistical analyses by the Statistical Analysis
      System for Windows software, with a significance level of 5%. RESULTS: The pelvic
      floor muscle contractility increased after PFMT, evaluated by sEMG (p=0.003) and
      digital palpation (p=0.001), accompanied by a decrease in urinary symptoms
      (p<0.001 for ICIQ-OAB scores e 0.036 for ICIQ UI-SF) as well as anterior pelvic
      organ prolapse (p=0.03). CONCLUSION: This preliminary study suggests that the
      applied PFMT program could be an effective way to increase PFM contractility, as
      well as to decrease both anterior pelvic organ prolapse and urinary symptoms, in
      postmenopausal women.

PMID- 25862492
TI  - Determining Family Needs on an Oncology Hospital Unit Using Interview, Art, and
      Survey.
AB  - A movement worldwide, and specifically new to our hospital, is the implementation
      of Patient- and Family-Centered Care. We were unsure, however, what the needs
      were of our patients' families. This triangulated study, on a 28-bed oncology
      unit, studied family members at the bedside. We asked family members what their
      needs were in a three-step process (open-ended interview, use of the Draw a
      Bridge art therapy technique, and the Family Inventory of Needs survey). Nineteen
      interviews revealed needs for physical comfort, emotional support, cultural
      sensitivity, recognition of help provided by family members and improved pain
      management. Art therapy revealed the stress of caregiving and helped to uncover
      unmet needs for interviewers to explore. The FIN identified that care at home
      after discharge was a major worry. Knowledge of family members' needs while a
      loved one is in the hospital allows for planning and provision of modalities to
      assist them in their caregiving. 

PMID- 25862493
TI  - Letter to the Editor on "Exposure to hazardous air pollutants and the risk of
      amyotrophic lateral sclerosis".

PMID- 25862494
TI  - Individual non-steroidal anti-inflammatory drugs and risk of acute kidney injury:
      A systematic review and meta-analysis of observational studies.
AB  - BACKGROUND: The association between acute kidney injury (AKI) and use of non
      steroidal anti-inflammatory drugs (NSAIDs) is well established. However, little
      is known about the comparative risk of individual NSAIDs, including specific COX
      2 inhibitors. METHODS: We conducted a systematic review and meta-analysis of
      cohort studies that reported relative risk, hazard ratio or standardized
      incidence ratio with 95% confidence comparing AKI risk in NSAID users versus non
      users. Pooled risk ratios and 95% confidence intervals for individual NSAIDs were
      calculated using random-effect, generic inverse variance methods. RESULTS: Five
      studies were identified and included in our data analysis. Pooled risk ratios
      were calculated for seven traditional NSAIDs and two specific COX-2 inhibitors,
      including indomethacin, piroxicam, ibuprofen, naproxen, sulindac, diclofenac,
      meloxicam, rofecoxib and celecoxib that were evaluated in at least two studies.
      Our meta-analysis was able to demonstrate a statistically significant elevated
      AKI risk among most of the included traditional NSAIDs. The pooled risk ratios
      were fairly consistent among individual traditional NSAIDs, ranging from 1.58 to
      2.11. Differences between pooled risk ratios did not reach statistical
      significance (p>=0.19 for each comparison). Elevated AKI risk was also observed
      in diclofenac, meloxicam, rofecoxib and celecoxib users, although did not achieve
      a statistical significance. CONCLUSION: A statistically significant elevated AKI
      risk among traditional NSAID users has been demonstrated in this meta-analysis.
      The pooled risk ratios among individual traditional NSAIDs were not significantly
      different. The pooled risk ratios of specific COX-2 inhibitors and the two
      traditional NSAIDs with the most COX-2 selectivity (diclofenac and meloxicam)
      were also comparable with other traditional NSAIDs even though they did not
      achieve a statistical significance.

PMID- 25862495
TI  - Heterogeneity of TERT promoter mutations status in squamous cell carcinomas of
      different anatomical sites.
AB  - Squamous cell carcinoma (SCC) can arise from different anatomical sites including
      the skin, head and neck, lung, esophagus, genital area, and so on. Despite the
      same histopathologic features and immunohistochemistry profile, the SCCs of
      different body sites can show tremendous differences in their presenting
      symptoms, risk factor associations, natural history, prognosis, and response to
      treatment. This may reflect the fact that SCCs are heterogenous and likely have
      unique molecular characteristics at different anatomical sites. Recurrent somatic
      mutations in the TERT promoter region were first reported in human melanomas.
      Subsequently, other tumors including cutaneous SCC were found to demonstrate high
      frequencies of the same mutations. However, the incidences of TERT promoter
      mutation in noncutaneous SCCs have not been systemically studied. We investigated
      the TERT promoter mutation status among SCCs from different sites. We collected
      84 cases of SCC from the skin (27), head and neck (12), lung (25), and cervix
      (10), as well as 10 cases of urothelial carcinoma with squamous differentiation
      (UC-SqD). We found that the frequencies of TERT promoter mutation among SCC of
      different sits are quite heterogenous: ~70% in skin SCC and UC-SqD, 16.67% in
      head and neck SCC, and 0% in lung and cervix SCC. These results may support the
      hypothesis of different carcinogenesis mechanisms of SCC in different sites. It
      also indicates that TERT promoter mutation could be a biomarker for
      distinguishing skin SCC or UC-SqD vs pulmonary SCC. 

PMID- 25862496
TI  - Diacylglycerol kinase eta1 is a high affinity isozyme for diacylglycerol.
AB  - Diacylglycerol kinase (DGK) eta plays important roles in various patho
      physiological events such as oncogenesis. In this study, we performed an
      enzymological characterization of DGKeta splice variant 1 (DGKeta1). The Km value
      for diacylglycerol was 0.14 mol%. Intriguingly, the Km value of DGKeta1 for
      diacylglycerol was at least 9-fold lower than those of other DGK isozymes
      including DGKalpha, indicating that DGKeta1 is a high affinity isozyme for
      diacylglycerol. Therefore, DGKeta1 is a unique DGK isozyme, which may function at
      particular membrane sites where only low concentrations of diacylglycerol are
      supplied.

PMID- 25862497
TI  - Arabidopsis mitochondrial voltage-dependent anion channel 3 (AtVDAC3) protein
      interacts with thioredoxin m2.
AB  - Voltage-dependent anion channels (VDACs) are conserved mitochondrial outer
      membrane proteins. A yeast two-hybrid screen identified interaction between
      Arabidopsis VDAC3 and the chloroplast protein thioredoxin m2 (AtTrx m2). This was
      confirmed via pull-down assay. A bimolecular fluorescence complementation assay
      located the interaction in mitochondria. AtVDAC3 and AtTrx m2 transcripts were
      expressed in multiple tissues and up-regulated by abiotic stress. Under NaCl
      stress, AtVDAC3 overexpression inhibited growth and increased H2O2 accumulation,
      while AtTrx m2 overexpression conferred resistance to NaCl and reduced H2O2.
      Results indicate that both AtVDAC3 and AtTrx m2 are involved in ROS signaling and
      play opposite roles in NaCl stress response. 

PMID- 25862498
TI  - Truncation of the A,A(*),A' helices segment impairs the actin bundling activity
      of mammalian eEF1A1.
AB  - Translation elongation factor eEF1A is a G-protein which has a crucial role in
      the ribosomal polypeptide elongation and possesses a number of non-translational
      functions. Here, we show that the A,A(*),A' helices segment of mammalian eEF1A is
      dispensable for the eEF1A*eEF1Balpha complex formation. The A,A(*),A' helices
      region did not interact with actin; however, its removal eliminates the actin
      bundling activity of eEF1A, probably due to the destruction of a dimeric
      structure of eEF1A. The translation function of monomers and the actin-bundling
      function of dimers of mammalian eEF1A is suggested. 

PMID- 25862499
TI  - Nitric oxide is a potent inhibitor of the cbb(3)-type heme-copper oxidases.
AB  - C-type heme-copper oxidases terminate the respiratory chain in many pathogenic
      bacteria, and will encounter elevated concentrations of NO produced by the immune
      defense of the host. Thus, a decreased sensitivity to NO in C-type oxidases would
      increase the survival of these pathogens. Here we have compared the inhibitory
      effect of NO in C-type oxidases to that in the mitochondrial A-type. We show that
      O2-reduction in both the Rhodobacter sphaeroides and Vibrio cholerae C-type
      oxidases is strongly and reversibly inhibited by submicromolar NO, with an
      inhibition pattern similar to the A-type. Thus, NO tolerance in pathogens with a
      C-type terminal oxidase has to rely mainly on other mechanisms. 

PMID- 25862500
TI  - Mesenchymal-stem-cell-derived exosomes accelerate skeletal muscle regeneration.
AB  - Mesenchymal stem cell (MSC) transplantation is used for treatment of many
      diseases. The paracrine role of MSCs in tissue regeneration is attracting
      particular attention. We investigate the role of MSC exosomes in skeletal muscle
      regeneration. MSC exosomes promote myogenesis and angiogenesis in vitro, and
      muscle regeneration in an in vivo model of muscle injury. Although MSC exosomes
      had low concentrations of muscle-repair-related cytokines, a number of repair
      related miRNAs were identified. This study suggests that the MSC-derived exosomes
      promote muscle regeneration by enhancing myogenesis and angiogenesis, which is at
      least in part mediated by miRNAs such as miR-494. 

PMID- 25862501
TI  - Structural insight into the calcium ion modulated interdomain electron transfer
      in cellobiose dehydrogenase.
AB  - Cellobiose dehydrogenase (CDH) from wood degrading fungi represents a subclass of
      oxidoreductases with unique properties. Consisting of two domains exhibiting
      interdomain electron transfer, this is the only known flavocytochrome involved in
      wood degradation. High resolution structures of the separated domains were
      solved, but the overall architecture of the intact protein and the exact
      interface of the two domains is unknown. Recently, it was shown that divalent
      cations modulate the activity of CDH and its pH optimum and a possible mechanism
      involving bridging of negative charges by calcium ions was proposed. Here we
      provide a structural explanation of this phenomenon confirming the interaction
      between negatively charged surface patches and calcium ions at the domain
      interface. 

PMID- 25862502
TI  - Distraction magnitude and frequency affects the outcome in juvenile idiopathic
      patients with growth rods: finite element study using a representative scoliotic
      spine model.
AB  - BACKGROUND CONTEXT: Growth rods are used to limit the progression of scoliosis
      without restraining the opportunity for the spine to grow. However, major
      complications like rod breakage, screw loosening, and altered sagittal contour
      have been encountered. OBJECTIVE: To analyse the effect of the magnitude of
      distraction forces on the T1-S1 growth, maximum von Mises stresses on the rods,
      sagittal contours, and load at the pedicle screw-bone interface and quantify the
      maximum stresses on the rod for a period of 24 months using different frequencies
      of distraction in a representative scoliotic spine model. STUDY DESIGN: A
      representative finite element model of a juvenile scoliotic spine was used to
      study the effect of magnitude and frequency of distraction on growth rods.
      METHODS: A representative scoliotic model was developed and instrumented using
      proximal foundation, distal foundation, and rods. Part 1: simulation steps
      comprised 6 months of growth under various distraction forces to analyze effects
      of distraction force on the biomechanics of the spine and instrument. Part 2:
      simulation steps comprised 24 months of growth under various intervals of
      distraction to analyze effects of distraction interval on the propensity of rod
      fracture. RESULTS: Part 1: an optimal distraction force exists for which the
      growth is sustained with minimum stress on the rod, lower loads at screw-bone
      interface, and unaltered sagittal contours. Part 2: the stresses on the rods were
      highest for 12-month distraction (2 distractions in 2 years) and lowest for 2
      month distraction (12 distractions in 2 years). CONCLUSIONS: The data and trend
      suggest that as the distraction forces vary so do the effects on spinal growth.
      The results of this study also signify the importance of shorter distraction
      period in reducing the stresses on the rods.

PMID- 25862503
TI  - Surgical correction of kyphotic deformity in a patient with Proteus syndrome.
AB  - BACKGROUND CONTEXT: Proteus syndrome (PS) is an extremely rare congenital
      disorder causing asymmetric overgrowth of different tissues. The etiology remains
      unclear. Limb deformities are common and often necessitate amputations. Only a
      few cases associated with spinal deformities have been described. PURPOSE: The
      aim was to report a rare case of PS associated with spinal deformity and its
      surgical management. STUDY DESIGN: A case of young boy with PS causing vertebral
      hypertrophy and kyphoscoliotic deformity, which was surgically corrected, is
      presented. METHODS: The patient was assessed clinically and with whole spine
      plain radiographs, computed tomography, and magnetic resonance imaging. Surgical
      correction was performed. RESULTS: Satisfactory correction of the deformity was
      achieved by posterior spinal fusion with instrumentation from T4-L5, five Ponte
      osteotomies T8-L1, and an L2 pedicle subtraction osteotomy. The kyphosis was
      corrected from 87 degrees  to 55 degrees ; there was improvement in all
      spinopelvic parameters. One year after surgery, there was maintenance of the
      deformity correction with no deterioration of the sagittal balance, and the
      patient was free of pain and had no loss of neurologic function. CONCLUSIONS:
      Proteus syndrome can be associated with spinal stenosis and deformity. Although
      the syndrome can be progressive in nature, the symptomatic spinal pathology
      should be treated appropriately.

PMID- 25862504
TI  - Computed Tomography Guided Subendplate Injection of Pingyangmycin for A Novel
      Rabbit Model of Slowly Progressive Disc Degeneration.
AB  - BACKGROUND: Different animal models are used in disc degenerative disease(DDD)
      research by now. To our knowledge, a functional animal model that mimics ischemic
      and slowly progressive disc degeneration of humans does not exist. STUDY DESIGN:
      An experimental animal study of disc degeneration. PURPOSE: To establish an
      ischemic and slowly progressive intervertebral disc (IVD) degeneration model with
      injection of Pingyangmycin into subchondral bone adjacent to the disc, using bone
      marrow needle guided by CT scan. METHODS: The subchondral bone adjacent to the
      lumbar IVDs (from L3/4 to L5/6) of eighteen rabbits was randomly injected with 3
      ml Pingyangmycin (PYM) solution (1.5mg/ml, PYM), 3 ml PBS (Vehicle control), or
      exteriorized but not injected with anything (Sham), with using bone marrow needle
      guided by CT scan. The degenerative process was investigated by using radiography
      and magnetic resonance imaging (MRI) at 1, 3, and 6 months postoperatively,
      combined with histological scoring, immunohistochemistry and real-time PCR
      analysis. RESULTS: Significant disc space narrowing was observed at 6 months in
      the discs adjacent to the subchondral bone injected with PYM, compared with the
      control groups(P<0.05). The MRI assessment also demonstrated a progressive loss
      of T2-weighted signal intensity postoperatively. The histological score increased
      significantly compared with that of the control groups from 3-month to the end
      point (P<0.05). The bone tissue area of the endplate increased significantly at
      the end point, compared with that of control groups(P<0.05). The results of
      molecular analysis showed significant increase of matrix metalloprotease(MMP)-3,
      a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-5, and
      marked reduction of aggrecan and type II collagen after 3 months at the mRNA
      levels in the discs of PYM group (P<0.05). The von willebrand factor (vWF)
      expression of PYM group also showed a significant reduction after 1
      month(P<0.05). CONCLUSIONS: Percutaneous injection of PYM into the subchondral
      bone adjacent to the lumbar IVDs of rabbits, using bone marrow needle guided by
      CT scan, can results in ischemic and slowly progressive disc degeneration model,
      which mimics the onset of human disc degeneration.

PMID- 25862506
TI  - 100 YEARS - Anzac, Vietnam to now.

PMID- 25862505
TI  - Differential diagnosis between tuberculous spondylodiscitis and pyogenic
      spontaneous spondylodiscitis: a multicenter descriptive and comparative study.
AB  - BACKGROUND CONTEXT: Although tuberculous and pyogenic spondylodiscitis are common
      causes of spinal infections, their protean manifestation complicates differential
      diagnosis. PURPOSE: The clinical, laboratory, and radiologic characteristics of
      tuberculous and pyogenic spontaneous spondylodiscitis were compared in this
      study. STUDY DESIGN: This multicenter retrospective study was conducted in 11
      teaching hospitals in the Republic of Korea from January 2011 to December 2013.
      PATIENT SAMPLE: Study subjects included adult patients (>=18 years) diagnosed
      with tuberculous (n=60) or pyogenic (n=117) spontaneous spondylodiscitis. OUTCOME
      MEASURES: Risk factors for tuberculous spondylodiscitis were determined, and
      their predictive performance was evaluated. METHODS: Multivariate logistic
      regression analysis was performed to determine predictors independently
      associated with tuberculous spondylodiscitis. Receiver-operating characteristic
      curve analysis using the presence or absence of risk factors was used to generate
      a risk index to identify patients with increased probability of tuberculous
      spondylodiscitis. RESULTS: Of 177 patients, multivariate logistic regression
      analysis showed that patients with tuberculous spondylodiscitis (n=60) were more
      frequently women, with increased nonlumbar spinal involvement and associated non
      spinal lesions, delayed diagnosis, higher serum albumin levels, reduced white
      blood cell counts, and lower C-reactive protein and procalcitonin levels. Among
      117 patients with pyogenic spondylodiscitis, the most frequent causative
      microorganism was Staphylococcus aureus (64.1%). The mean diagnostic delay was
      significantly shorter, which may reflect higher clinical expression leading to
      earlier diagnosis. A combination of clinical data and biomarkers had better
      predictive value for differential diagnosis compared with biomarkers alone, with
      an area under the curve of 0.93, and sensitivity, specificity, and positive and
      negative predictive values of 95.0%, 79.5%, 70.4%, and 96.9%, respectively.
      CONCLUSIONS: This study provides guidance for clinicians to predict the causative
      organisms of spondylodiscitis in uncertain situations and before culture or
      pathologic examinations. Clinical data and single biomarkers combined can be
      useful for differential diagnoses between tuberculous and pyogenic
      spondylodiscitis.

PMID- 25862507
TI  - Magnitude of preoperative cervical lordotic compensation and C2-T3 angle are
      correlated to increased risk of postoperative sagittal spinal pelvic malalignment
      in adult thoracolumbar deformity patients at 2-year follow-up.
AB  - BACKGROUND CONTEXT: Cervical deformity (CD) is prevalent among patients with
      adult spinal deformity (ASD). The effect of baseline cervical alignment on
      achieving optimal thoracolumbar alignment in ASD surgery is unclear. PURPOSE:
      This study assesses the relationship between preoperative (preop) cervical spinal
      parameters and global alignment after thoracolumbar ASD surgery at 2-year follow
      up. STUDY DESIGN/SETTING: This study is a retrospective review of a multicenter,
      prospective database. PATIENT SAMPLE: Surgical ASD patients with 2-year follow-up
      and cervical X-rays were included. OUTCOME MEASURES: The outcome measures were
      radiographic parameters and self-reported health-related quality-of-life measures
      (Short-Form 36 [SF-36], Oswestry Disability Index [ODI], and Scoliosis Research
      Society 22 [SRS-22]). METHODS: Surgical ASD patients of 18 years and older with
      scoliosis greater than or equal to 20 degrees  and one of the following
      radiographic parameters were included: sagittal vertical axis (SVA) greater than
      or equal to 5 cm, pelvic tilt (PT) greater than or equal to 25 degrees , or
      thoracic kyphosis (TK) greater than 60 degrees . The SRS-Schwab sagittal
      modifiers (PT, global alignment, and pelvic incidence and lumbar lordosis [PI
      LL]) were assessed at 2-year postoperatively as either normal ("0") or abnormal
      ("+" or "++"). Patients were classified in the aligned group (AG) or malaligned
      group (MG) at 2-year follow-up if all three sagittal modifiers were normal or
      abnormal, respectively. Patients were assessed for CD based on the following
      criteria: C2-C7 SVA greater than 4 cm, C2-C7 SVA less than 4 cm, cervical
      kyphosis (CL greater than 0), cervical lordosis (CL less than 0), any deformity
      (C2-C7 SVA greater than 4 cm or CL greater than 0), and both CD (C2-C7 SVA
      greater than 4 cm and CL greater than 0). Univariate testing was performed using
      t or chi-square test, looking at the following preop parameters: CD, C2-C7 SVA,
      C2-T3 SVA, CL, T1 slope (T1S), T1S-CL, C2-T3 angle, LL, TK, PT, C7-S1 SVA, and PI
      LL. RESULTS: One hundred four patients met the initial inclusion criteria with 70
      in the AG and 34 in MG. Preoperative, patients in the MG had a higher CL (11.7
      vs. 4.9, p=.03), higher C2-T3 angle (13.59 vs 4.9 p=.01), higher PT (p<.0001),
      higher SVA (p<.0001), and higher PI-LL (p<.0001) compared with the AG.
      Interestingly, the prevalence of CD at baseline was similar for both groups.
      There was no statistically significant difference among groups in the amount of
      improvement more than 2 years on the ODI or the Physical Component Summary of SF
      36. CONCLUSIONS: Patients with sagittal spinal malalignment associated with
      significant cervical compensatory lordosis are at increased risk of realignment
      failure at 2-year follow-up. Assessment of the degree of cervical compensation
      may be helpful in preop evaluation to assist in realignment outcome prediction.

PMID- 25862509
TI  - Surgical outcomes by age at the time of surgery in the treatment of congenital
      scoliosis in children under age 10 years.
AB  - BACKGROUND CONTEXT: There is little information regarding the surgical outcomes
      with regard to the timing of surgery in children under age 10 years for
      congenital scoliosis with a long-term follow-up. PURPOSE: The purpose of this
      study was to compare the surgical outcomes for congenital scoliosis in children 6
      years or older but less than 10 years of age. STUDY DESIGN: This is a
      retrospective study. PATIENT SAMPLE: Eighteen congenital scoliosis patients under
      age 10 years at the time of surgery were treated by posterior hemivertebra
      resection and bilateral pedicle screw fixation. OUTCOME MEASURES: Outcome
      measures are radiological outcomes (plain radiographs and computed tomography)
      and complications. METHODS: Eighteen congenital scoliosis patients (n=18) under
      age 10 years at the time of surgery were treated by posterior hemivertebra
      resection and bilateral pedicle screw fixation. These cases were retrospectively
      studied and had a minimum of 7-year follow-up. We assigned patients into two
      groups: Group 1 (n=9) patients who had surgery before 6 years of age and Group 2
      (n=9) those who had surgery after 6 years of age. RESULTS: The groups were not
      found to be statistically different in operative time, blood loss, and follow-up
      period. In the Group 1, the mean Cobb angle of the main curve was 32.4 degrees 
      before surgery, 6.4 degrees  after surgery, and 9.1 degrees  at last follow-up.
      In the Group 2, the mean Cobb angle of the main curve was 36.5 degrees  before
      surgery, 10.4 degrees  after surgery, and 14.5 degrees  at last follow-up. There
      was significantly better deformity correction of main curve immediate
      postoperatively and at last follow-up in Group 1. No significant difference was
      observed in growth rate of the vertebral body and spinal canal parameters
      comparing the two groups at the vertebra with or without screws. There was no
      crankshaft phenomena, no clinical or radiographic features suggestive of spinal
      stenosis during follow-up, and no major vascular or neurological complications
      related to the pedicle screws in either group. CONCLUSIONS: In congenital
      scoliosis patients, posterior hemivertebra resection after pedicle screw fixation
      before the age of 6 years had significantly better deformity correction and did
      not cause a negative effect on the growth of vertebral body or spinal canal
      compared with the group treated after 6 years of age. Therefore, early surgical
      correction of a congenital hemivertebra in children under 6 years of age, before
      structural changes occur, effectively achieves a more satisfactory correction
      without causing iatrogenic spinal stenosis or neurologic complications compared
      with children older than 6 years but under 10 years of age.

PMID- 25862508
TI  - Trunk motor control deficits in acute and subacute low back pain are not
      associated with pain or fear of movement.
AB  - BACKGROUND CONTEXT: A subgroup of patients with acute to subacute low back pain
      (LBP) presenting with trunk movement control deficits, pain provocation with
      segmental testing, and segmental hypermobility have been clinically identified as
      having movement coordination impairments (MCIs) of the trunk. It is hypothesized
      that these patients have proprioceptive, postural, and movement control
      impairments of the trunk associated with LBP. Although trunk control impairments
      have been identified in patients with chronic LBP, they have not been
      investigated in this subgroup or closer to symptom onset. PURPOSE: The purpose of
      the study was to identify trunk motor control (postural control and movement
      precision) impairments in a subgroup of patients with acute to subacute LBP who
      have been clinically identified to have MCIs and determine association of these
      impairments with pain and fear of movement. STUDY DESIGN/SETTING: The study
      design includes observational design, university biomechanics laboratory, and
      clinical practice. PATIENT SAMPLE: Thirty-three patients with acute to subacute
      LBP presenting with trunk MCIs and 33 healthy controls matched with gender, age,
      and body mass index were identified. OUTCOME MEASURES: Self-report measures
      included Numeric Pain Rating Scale, Oswestry Disability Index Questionnaire, and
      Fear-Avoidance Beliefs Questionnaire and physiologic measures included postural
      control and movement precision. METHODS: Center-of-pressure movement was measured
      while subjects attempted to volitionally control trunk posture and movement while
      sitting on a platform with a hemisphere mounted underneath. This created an
      unstable surface that required coordinated trunk control to maintain an upright
      seated posture. Postural control was tested using eyes-open and -closed balance
      protocols. Movement precision was tested with a dynamic control test requiring
      movement of the center of pressure along a discrete path. Group trunk motor
      control performance was compared with analysis of variance and t test.
      Performance association with pain and fear of movement were assessed with Pearson
      correlations. RESULTS: Patients' postural control in the eyes-closed condition
      (p=.02) and movement precision (p=.04) were significantly impaired compared with
      healthy controls, with moderate-to-large group difference effect sizes. These
      trunk motor control impairments were not significantly associated with the
      patients self-reported pain characteristics and fear of movement. CONCLUSIONS:
      Patients with clinical identification of trunk MCIs demonstrated decreased trunk
      motor control, suggesting that impairments in proprioception, motor output, or
      central processing occur early in the back pain episode. This information may
      help to guide interventions to address these specific limitations, improving
      delivery of care.

PMID- 25862510
TI  - Quality of life after en bloc resection of tumors in the mobile spine.
AB  - BACKGROUND CONTEXT: Little has been reported regarding the patient-centered
      quality-of-life (QOL) outcomes after en bloc spondylectomy (ES). Despite lower
      local recurrence rates, it is unknown whether outcomes justify the surgical
      morbidity. PURPOSE: The purpose of this study was to report on patient QOL after
      ES as measured by validated instruments and to identify factors that may predict
      better postoperative QOL. STUDY DESIGN: This is a retrospective case-control
      study (Level III). PATIENT SAMPLE: Thirty-five consecutive patients with mobile
      spine tumors were included. Twenty-seven patients underwent en bloc resection,
      whereas 8 patients received definitive radiation and no surgery. Minimum follow
      up was 6 months (median, 32 months). OUTCOME MEASURES: The outcome measures were
      European Quality Group 5-Dimensional Questionnaire (EQ5D), four Patient-Reported
      Outcome Measurement Information System (PROMIS) short-form metrics, Neck
      Disability Index, and Oswestry Disability Index (ODI). METHODS: We performed
      statistical comparisons between the surgery and radiation groups, of the general
      US population, and within the study group itself to identify predictors of higher
      QOL scores. RESULTS: We identified a significant difference in QOL between the
      surgery and radiation groups in only one instrument, PROMIS pain interference,
      with surgery having more pain interference (15.7 vs. 10.1, p=.04). For most
      metrics, including EQ5D, pain interference, pain behavior, and ODI, scores were
      around one standard deviation worse than the US population mean. Multivariable
      linear regression for each instrument demonstrated that preoperative factors such
      as better performance status, tumor location in the cervical spine, lack of
      mechanical back or neck pain, and shorter fusion span were independently
      predictive of better QOL scores. Postoperative factors such as poor performance
      status, chronic narcotic use, and local recurrence were more dominant than
      preoperative factors in predicting worse QOL. CONCLUSIONS: Patients may
      experience more pain interference after surgery as opposed to definitive
      radiotherapy, but we did not identify a difference for most metrics. Quality of
      life in our study group was significantly worse than the general population for
      most metrics. Cervical tumors, lack of mechanical pain, better baseline
      performance status, and less extensive surgery predict better QOL after surgery.

PMID- 25862511
TI  - Polyetheretherketone (PEEK) intervertebral cage as a cause of chronic systemic
      allergy: a case report.
AB  - BACKGROUND CONTEXT: Polyetheretherketone (PEEK) is an organic polymer
      thermoplastic with strong mechanical and chemical resistance properties. It has
      been used in industry to fabricate items for demanding applications such as
      bearings, piston parts, compressor plate valves, and cable insulation. Since the
      early 1980s, polyetheretherketone polymers have been increasingly used in
      orthopedic and spinal surgery applications. Numerous studies and years of
      clinical experience have confirmed the biocompatibility of this material.
      PURPOSE: The purpose of the study was to report a case of chronic systemic
      allergy after anterior cervical decompression and fusion (ACDF) and implantation
      of an intervertebral PEEK cage, with resolution of symptoms after removal of PEEK
      cage. STUDY DESIGN/SETTING: This study is a case report with clinical evidence
      for allergy to PEEK. METHODS: The methods involve clinical findings and review of
      current literature. RESULTS: After ACDF and implantation of an intervertebral
      PEEK cage, the patient had developed an angioedema-like picture marked by severe
      redness, itching, swelling of his tongue, and skin thickening. A skin patch test
      was positive for PEEK. Removal of the implant resulted in the resolution of his
      allergy symptoms shortly after surgery. CONCLUSIONS: Tissue reactions to PEEK are
      extremely rare. Herein, we present the first report of a chronic allergic
      response to interbody PEEK material.

PMID- 25862512
TI  - An investigation into axial impacts of the cervical spine using digital image
      correlation.
AB  - BACKGROUND CONTEXT: High-energy impacts are commonly encountered during sports
      such as rugby union. Although catastrophic injuries resulting from such impacts
      are rare, the consequences can be devastating for all those involved. A greater
      level of understanding of cervical spine injury mechanisms is required, with the
      ultimate aim of minimizing such injuries. PURPOSE: The present study aimed to
      provide a greater understanding of cervical spine injury mechanisms, by
      subjecting porcine spinal specimens to impact conditions based on those measured
      in vivo. The impacts were investigated using high-speed digital image correlation
      (DIC), a method not previously adopted for spinal impact research. STUDY DESIGN:
      This was an in vitro biomechanical study. METHODS: Eight porcine specimens were
      impacted using a custom-made rig. The cranial and caudal axial loads were
      measured at 1 MHz. Video data were captured with two cameras at 4 kHz, providing
      measurements of the three-dimensional deformation and surface strain field of the
      specimens using DIC. RESULTS: The injuries induced on the specimens were similar
      to those observed clinically. The mean+/-standard deviation peak caudal load was
      6.0+/-2.1 kN, which occurred 5.6+/-1.1 ms after impact. Damage observable with
      the video data occurred in six specimens, 5.4+/-1.1 ms after impact, and the peak
      surface strain at fracture initiation was 4.6+/-0.5%. CONCLUSIONS: This study has
      provided an unprecedented insight into the injury mechanisms of the cervical
      spine during impact loading. The posture represents a key factor in injury
      initiation, with lordosis of the spine increasing the likelihood of injury.

PMID- 25862513
TI  - Spatial and temporal mapping of heterogeneity in liposome uptake and
      microvascular distribution in an orthotopic tumor xenograft model.
AB  - Existing paradigms in nano-based drug delivery are currently being challenged.
      Assessment of bulk tumor accumulation has been routinely considered an indicative
      measure of nanomedicine potency. However, it is now recognized that the
      intratumoral distribution of nanomedicines also impacts their therapeutic effect.
      At this time, our understanding of the relationship between the bulk (i.e., macro
      ) tumor accumulation of nanocarriers and their intratumoral (i.e., micro-)
      distribution remains limited. Liposome-based drug formulations, in particular,
      suffer from diminished efficacy in vivo as a result of transport-limiting
      properties, combined with the heterogeneous nature of the tumor microenvironment.
      In this report, we perform a quantitative image-based assessment of macro- and
      microdistribution of liposomes. Multi-scalar assessment of liposome distribution
      was enabled by a stable formulation which co-encapsulates an iodinated contrast
      agent and a near-infrared fluorescence probe, for computed tomography (CT) and
      optical microscopy, respectively. Spatio-temporal quantification of tumor uptake
      in orthotopic xenografts was performed using CT at the bulk tissue level, and
      within defined sub-volumes of the tumor (i.e., rim, periphery and core). Tumor
      penetration and relative distribution of liposomes were assessed by fluorescence
      microscopy of whole tumor sections. Microdistribution analysis of whole tumor
      images exposed a heterogeneous distribution of both liposomes and tumor
      vasculature. Highest levels of liposome uptake were achieved and maintained in
      the well-vascularized tumor rim over the study period, corresponding to a
      positive correlation between liposome and microvascular density. Tumor
      penetration of liposomes was found to be time-dependent in all regions of the
      tumor however independent of location in the tumor. Importantly, a multi-scalar
      comparison of liposome distribution reveals that macro-accumulation in tissues
      (e.g., blood, whole tumor) may not reflect micro-accumulation levels present
      within specific regions of the tumor as a function of time. 

PMID- 25862514
TI  - Multifunctional poly(methacrylate) polyplex libraries: A platform for gene
      delivery inspired by nature.
AB  - Polymer-based gene delivery systems have enormous potential in biomedicine, but
      their efficiency is often limited by poor biocompatibility. Poly(methacrylate)s
      (PMAs) are an interesting class of polymers which allow to explore structure
      activity relationships of polymer functionalities for polyplex formation in
      oligonucleotide delivery. Here, we synthesized and tested a library of PMA
      polymers, containing functional groups contributing to the different steps of
      gene delivery, from oligonucleotide complexation to cellular internalization and
      endosomal escape. By variation of the molar ratios of the individual building
      blocks, the physicochemical properties of the polymers and polyplexes were fine
      tuned to reduce toxicity as well as to increase activity of the polyplexes. To
      further enhance transfection efficiency, a cell-penetrating peptide (CPP)-like
      functionality was introduced on the polymeric backbone. With the ability to
      synthesize large libraries of polymers in parallel we also developed a workflow
      for a mid-to-high throughput screening, focusing first on safety parameters that
      are accessible by high-throughput approaches such as blood compatibility and
      toxicity towards host cells and only at a later stage on more laborious tests for
      the ability to deliver oligonucleotides. To arrive at a better understanding of
      the molecular basis of activity, furthermore, the effect of the presence of
      heparan sulfates on the surface of host cells was assessed and the mechanism of
      cell entry and intracellular trafficking investigated for those polymers that
      showed a suitable pharmacological profile. Following endocytic uptake, rapid
      endosomal release occurred. Interestingly, the presence of heparan sulfates on
      the cell surface had a negative impact on the activity of those polyplexes that
      were sensitive to decomplexation by heparin in solution. In summary, the
      screening approach identified two polymers, which form polyplexes with high
      stability and transfection capacity exceeding the one of poly(ethylene imine)
      also in the presence of serum. 

PMID- 25862515
TI  - Site-specific albumination of a therapeutic protein with multi-subunit to prolong
      activity in vivo.
AB  - Albumin fusion/conjugation (albumination) has been an effective method to prolong
      in vivo half-life of therapeutic proteins. However, its broader application to
      proteins with complex folding pathway or multi-subunit is restricted by incorrect
      folding, poor expression, heterogeneity, and loss of native activity of the
      proteins linked to albumin. We hypothesized that the site-specific conjugation of
      albumin to a permissive site of a target protein will expand the utilities of
      albumin as a therapeutic activity extender to proteins with a complex structure.
      We show here the genetic incorporation of a non-natural amino acid (NNAA)
      followed by chemoselective albumin conjugation to prolong therapeutic activity in
      vivo. Urate oxidase (Uox), a therapeutic enzyme for treatment of hyperuricemia,
      is a homotetramer with multiple surface lysines, limiting conventional approaches
      for albumination. Incorporation of p-azido-l-phenylalanine into two predetermined
      positions of Uox allowed site-specific linkage of dibenzocyclooctyne-derivatized
      human serum albumin (HSA) through strain-promoted azide-alkyne cycloaddition
      (SPAAC). The bio-orthogonality of SPAAC resulted in the production of a
      chemically well-defined conjugate, Uox-HSA, with a retained enzymatic activity.
      Uox-HSA had a half-life of 8.8 h in mice, while wild-type Uox had a half-life of
      1.3 h. The AUC increased 5.5-fold (1657 vs. 303 mU/mL x h). These results clearly
      demonstrated that site-specific albumination led to the prolonged enzymatic
      activity of Uox in vivo. Site-specific albumination enabled by NNAA incorporation
      and orthogonal chemistry demonstrates its promise for the development of long
      acting protein therapeutics with high potency and safety. 

PMID- 25862516
TI  - Insights into the impact of online physician reviews on patients' decision
      making: randomized experiment.
AB  - BACKGROUND: Physician-rating websites combine public reporting with social
      networking and offer an attractive means by which users can provide feedback on
      their physician and obtain information about other patients' satisfaction and
      experiences. However, research on how users evaluate information on these portals
      is still scarce and only little knowledge is available about the potential
      influence of physician reviews on a patient's choice. OBJECTIVE: Starting from
      the perspective of prospective patients, this paper sets out to explore how
      certain characteristics of physician reviews affect the evaluation of the review
      and users' attitudes toward the rated physician. We propose a model that relates
      review style and review number to constructs of review acceptance and check it
      with a Web-based experiment. METHODS: We employed a randomized 2x2 between
      subject, factorial experiment manipulating the style of a physician review
      (factual vs emotional) and the number of reviews for a certain physician (low vs
      high) to test our hypotheses. A total of 168 participants were presented with a
      Web-based questionnaire containing a short description of a dentist search
      scenario and the manipulated reviews for a fictitious dental physician. To
      investigate the proposed hypotheses, we carried out moderated regression analyses
      and a moderated mediation analysis using the PROCESS macro 2.11 for SPSS version
      22. RESULTS: Our analyses indicated that a higher number of reviews resulted in a
      more positive attitude toward the rated physician. The results of the regression
      model for attitude toward the physician suggest a positive main effect of the
      number of reviews (mean [low] 3.73, standard error [SE] 0.13, mean [high] 4.15,
      SE 0.13). We also observed an interaction effect with the style of the review-if
      the physician received only a few reviews, fact-oriented reviews (mean 4.09, SE
      0.19) induced a more favorable attitude toward the physician compared to
      emotional reviews (mean 3.44, SE 0.19), but there was no such effect when the
      physician received many reviews. Furthermore, we found that review style also
      affected the perceived expertise of the reviewer. Fact-oriented reviews (mean
      3.90, SE 0.13) lead to a higher perception of reviewer expertise compared to
      emotional reviews (mean 3.19, SE 0.13). However, this did not transfer to the
      attitude toward the physician. A similar effect of review style and number on the
      perceived credibility of the review was observed. While no differences between
      emotional and factual style were found if the physician received many reviews, a
      low number of reviews received lead to a significant difference in the perceived
      credibility, indicating that emotional reviews were rated less positively (mean
      3.52, SE 0.18) compared to fact-oriented reviews (mean 4.15, SE 0.17). Our
      analyses also showed that perceived credibility of the review fully mediated the
      observed interaction effect on attitude toward the physician. CONCLUSIONS:
      Physician-rating websites are an interesting new source of information about the
      quality of health care from the patient's perspective. This paper makes a unique
      contribution to an understudied area of research by providing some insights into
      how people evaluate online reviews of individual doctors. Information attributes,
      such as review style and review number, have an impact on the evaluation of the
      review and on the patient's attitude toward the rated doctor. Further research is
      necessary to improve our understanding of the influence of such rating sites on
      the patient's choice of a physician.

PMID- 25862518
TI  - When less is more: maintenance therapy in colorectal cancer.

PMID- 25862517
TI  - Maintenance treatment with capecitabine and bevacizumab in metastatic colorectal
      cancer (CAIRO3): a phase 3 randomised controlled trial of the Dutch Colorectal
      Cancer Group.
AB  - BACKGROUND: The optimum duration of first-line treatment with chemotherapy in
      combination with bevacizumab in patients with metastatic colorectal cancer is
      unknown. The CAIRO3 study was designed to determine the efficacy of maintenance
      treatment with capecitabine plus bevacizumab versus observation. METHODS: In this
      open-label, phase 3, randomised controlled trial, we recruited patients in 64
      hospitals in the Netherlands. We included patients older than 18 years with
      previously untreated metastatic colorectal cancer, with stable disease or better
      after induction treatment with six 3-weekly cycles of capecitabine, oxaliplatin,
      and bevacizumab (CAPOX-B), WHO performance status of 0 or 1, and adequate bone
      marrow, liver, and renal function. Patients were randomly assigned (1:1) to
      either maintenance treatment with capecitabine and bevacizumab (maintenance
      group) or observation (observation group). Randomisation was done centrally by
      minimisation, with stratification according to previous adjuvant chemotherapy,
      response to induction treatment, WHO performance status, serum lactate
      dehydrogenase concentration, and treatment centre. Both patients and
      investigators were aware of treatment assignment. We assessed disease status
      every 9 weeks. On first progression (defined as PFS1), patients in both groups
      were to receive the induction regimen of CAPOX-B until second progression (PFS2),
      which was the study's primary endpoint. All endpoints were calculated from the
      time of randomisation. Analyses were done by intention to treat. This trial is
      registered with ClinicalTrials.gov, number NCT00442637. FINDINGS: Between May 30,
      2007, and Oct 15, 2012, we randomly assigned 558 patients to either the
      maintenance group (n=279) or the observation group (n=279). Median follow-up was
      48 months (IQR 36-57). The primary endpoint of median PFS2 was significantly
      improved in patients on maintenance treatment, and was 8.5 months in the
      observation group and 11.7 months in the maintenance group (HR 0.67, 95% CI 0.56
      0.81, p<0.0001). This difference remained significant when any treatment after
      PFS1 was considered. Maintenance treatment was well tolerated, although the
      incidence of hand-foot syndrome was increased (64 [23%] patients with hand-foot
      skin reaction during maintenance). The global quality of life did not deteriorate
      during maintenance treatment and was clinically not different between treatment
      groups. INTERPRETATION: Maintenance treatment with capecitabine plus bevacizumab
      after six cycles of CAPOX-B in patients with metastatic colorectal cancer is
      effective and does not compromise quality of life. FUNDING: Dutch Colorectal
      Cancer Group (DCCG). The DCCG received financial support for the study from the
      Commissie Klinische Studies (CKS) of the Dutch Cancer Foundation (KWF), Roche,
      and Sanofi-Aventis.

PMID- 25862519
TI  - Peri-operative Levosimendan in Patients Undergoing Cardiac Surgery: An Overview
      of the Evidence.
AB  - Levosimendan, a calcium sensitiser, has recently emerged as a valuable agent in
      the peri-operative management of cardiac surgery patients. Levosimendan is a
      calcium-sensitising ionodilator. By binding to cardiac troponin C and reducing
      its calcium-binding co-efficient, it enhances myofilament responsiveness to
      calcium and thus enhances myocardial contractility without increasing oxygen
      demand. Current evidence suggests that levosimendan enhances cardiac function
      after cardiopulmonary bypass in patients with both normal and reduced left
      ventricular function. In addition to being used as post-operative rescue therapy
      for low cardiac output syndrome, a pre-operative levosimendan infusion in high
      risk patients with poor cardiac function may reduce inotropic requirements, the
      need for mechanical support, the duration of intensive care admissions as well as
      post-operative mortality. Indeed, it is these higher-risk patients who may
      experience a greater degree of benefit. Larger, multicentre randomised trials in
      cardiac surgery will help to elucidate the full potential of this agent. 

PMID- 25862521
TI  - Evidence for a synchronization of hormonal states between humans and dogs during
      competition.
AB  - Social interactions with humans have been shown to influence hormonal processes
      in dogs, but it is unclear how the hormonal states of humans factor into this
      relationship. In this study, we explored the associations between changes in the
      cortisol levels of dogs with humans' hormonal changes, behavior, and perceptions
      of their performance at an agility competition. A total of 58 dogs and their
      handlers (44 women, 14 men) provided saliva samples before and after competing.
      Dogs' saliva samples were later assayed for cortisol and humans' samples for
      cortisol and testosterone. Following the competition, handler-dog interactions
      were observed for affiliative and punitive behavior towards their dogs, and
      handlers completed questionnaires that included personal ratings of their
      performance. Structural equation modeling revealed that elevations in handlers'
      cortisol levels were associated with increases in their dogs' cortisol levels.
      Handlers' affiliative and punitive behaviors towards their dogs following
      competition were associated with their ratings of their performance, but these
      variables were unrelated to changes in their own cortisol levels and their dogs',
      implying their behavior did not mediate the relationship. These findings suggest
      that changes in the hormonal states were reflected between humans and their dogs,
      and this relationship was not due to handlers' perceptions of their performance
      or the behaviors we observed during post-competition social interactions. This
      study is one of the first to provide evidence for a synchronization of hormonal
      changes between species. 

PMID- 25862522
TI  - The effect of implant number and position on the stress behavior of mandibular
      implant retained overdentures: A three-dimensional finite element analysis.
AB  - The present study evaluated the effects of ball anchor abutment attached to
      implants with a 4.30 mm diameter and 11 mm insert length on stress distribution
      in a patient without any remaining teeth in the lower jaw. In the study, the
      stress analysis was performed for five different configurations (2 with 4 implant
      supported and 3 with 2 implant-supported) and three different loading types using
      ANSYS Workbench software. The stresses measured in the 4 implant-supported models
      were lower compared to the stresses measured in the 2 implant-supported models.
      The stresses on the implants intensified on the cervical region of the implants.
      When the effects of the loading sites on the stress were examined, the loading on
      the first molar tooth produced the highest stresses on the implants.

PMID- 25862520
TI  - Mixed-effects model of epithelial-mesenchymal transition reveals rewiring of
      signaling networks.
AB  - The type II epithelial-mesenchymal transition (EMT) produces airway fibrosis and
      remodeling, contributing to the severity of asthma and chronic obstructive
      pulmonary disease. While numerous studies have been done on the mechanisms of the
      transition itself, few studies have investigated the system effects of EMT on
      signaling networks. Here, we use mixed effects modeling to develop a
      computational model of phospho-protein signaling data that compares human small
      airway epithelial cells (hSAECs) with their EMT-transformed counterparts across a
      series of perturbations with 8 ligands and 5 inhibitors, revealing previously
      uncharacterized changes in signaling in the EMT state. Strong couplings between
      menadione, TNFalpha and TGFbeta and their known phospho-substrates were revealed
      after mixed effects modeling. Interestingly, the overall phospho-protein response
      was attenuated in EMT, with loss of Mena and TNFalpha coupling to heat shock
      protein (HSP)-27. These differences persisted after correction for EMT-induced
      changes in phospho-protein substrate abundance. Construction of network topology
      maps showed significant changes between the two cellular states, including a
      linkage between glycogen synthase kinase (GSK)-3alpha and small body size/mothers
      against decapentaplegic (SMAD)2. The model also predicted a loss of p38 mitogen
      activated protein kinase (p38MAPK)-independent HSP27 signaling, which we
      experimentally validated. We further characterized the relationship between HSP27
      and signal transducers and activators of transcription (STAT)3 signaling, and
      determined that loss of HSP27 following EMT is only partially responsible for the
      downregulation of STAT3. These rewired connections represent therapeutic targets
      that could potentially reverse EMT and restore a normal phenotype to the
      respiratory mucosa. 

PMID- 25862523
TI  - Morphologic comparison of preformed orbital meshes.
AB  - PURPOSE: Preformed orbital titanium meshes have been introduced to improve
      outcomes in the treatment of orbital wall fractures. This study evaluated the
      geometry of different commercially available orbital meshes and compared them
      with an average human orbit. MATERIALS AND METHODS: Seven commercially available
      preformed orbital meshes were scanned using an optical scanner. For comparison,
      an average orbit was generated from 113 computed tomographic scans of unaffected
      orbits. Meshes and the average orbit were compared by registration and the
      calculation of congruence. RESULTS: All meshes showed a high similarity within a
      +/-1.5-mm deviation corridor. Major differences were seen in the slope between
      the orbital floor and the medial wall and in the upturning toward the lateral
      orbital rim. CONCLUSION: Preformed orbital meshes conform highly to an average
      orbit, but differ in size and geometry. Using special software, the best fitting
      mesh could be chosen preoperatively to improve surgical outcome if its geometry
      were published.

PMID- 25862524
TI  - [Frequent proctologic findings from a surgeon's viewpoint].
AB  - Patients with anal complaints require a high level of sensitivity of the involved
      healthcare professionals. A large variety of different pathological changes lead
      to very similar clinical symptoms. A carefully guided history interview is able
      to target in many cases the underlying condition. Treatment should not be
      performed before definite exclusion of any malignant disease. However, patients
      most of all blame hemorrhoids for any anal physical discomfort and visit the
      physician with high expectations in treatment of their supposed disease. The
      following summary ranks anal diseases by frequency considering their clinical
      appearance and delimitation and provides an overview of symptoms associated with
      hemorrhoids. 

PMID- 25862525
TI  - The aryl hydrocarbon receptor/microRNA-212/132 axis in T cells regulates IL-10
      production to maintain intestinal homeostasis.
AB  - Aryl hydrocarbon receptor (Ahr), a transcription factor, plays a critical role in
      autoimmune inflammation of the intestine. In addition, microRNAs (miRNAs), small
      non-coding oligonucleotides, mediate pathogenesis of inflammatory bowel diseases
      (IBD). However, the precise mechanism and interactions of these molecules in IBD
      pathogenesis have not yet been investigated. We analyzed the role of Ahr and Ahr
      regulated miRNAs in colonic inflammation. Our results show that deficiency of Ahr
      in intestinal epithelial cells in mice exacerbated inflammation in dextran sodium
      sulfate-induced colitis. Deletion of Ahr in T cells attenuated colitis, which was
      manifested by suppressed Th17 cell infiltration into the lamina propria.
      Candidate miRNA analysis showed that induction of colitis elevated expression of
      the miR-212/132 cluster in the colon of wild-type mice, whereas in Ahr (-/-)
      mice, expression was clearly lower. Furthermore, miR-212/132(-/-) mice were
      highly resistant to colitis and had reduced levels of Th17 cells and elevated
      levels of IL-10-producing CD4(+) cells. In vitro analyses revealed that induction
      of type 1 regulatory T (Tr1) cells was significantly elevated in miR-212/132(-/-)
      T cells with increased c-Maf expression. Our findings emphasize the vital role of
      Ahr in intestinal homeostasis and suggest that inhibition of miR-212/132
      represents a viable therapeutic strategy for treating colitis. 

PMID- 25862526
TI  - Comparative study of functional and aesthetically outcomes of reverse digital
      artery and reverse dorsal homodigital island flaps for fingertip repair.
AB  - This retrospective study was designed to compare functional and cosmetic outcomes
      of the reverse digital artery island flap and reverse dorsal homodigital island
      flap in fingertip repair. A total of 23 patients were followed for 24 to 30
      months. The reverse digital artery island flap was used in 12 patients, and
      reverse dorsal homodigital island flap in another 11 patients. Flap sensibility
      was assessed using the Semmes-Weinstein monofilament test and static 2-point
      discrimination test. Patient satisfaction, active motion of the finger joints,
      complications and cold intolerance were evaluated. The static 2-point
      discrimination and Michigan Hand Outcomes Questionnaire (appearance) of the
      fingers treated with a reverse digital artery flap were significantly better than
      those with a reverse dorsal homodigital flap. The static 2-point discrimination
      of the skin-grafted donor sides after dorsal homodigital flap were poorer than
      that in the contralateral finger. No significant differences were found between
      the two flaps for pressure or touch sensibility, active ranges of digital motion,
      complications and cold intolerance. LEVEL OF EVIDENCE: III.

PMID- 25862527
TI  - Does flexing the arm really affect ulnar motor conduction velocity across the
      elbow?

PMID- 25862528
TI  - Aerobic exercise intervention in young people with schizophrenia spectrum
      disorders; improved fitness with no change in hippocampal volume.

PMID- 25862529
TI  - Effect of direct eye contact in women with PTSD related to interpersonal trauma:
      Psychophysiological interaction analysis of connectivity of an innate alarm
      system.
AB  - In healthy individuals, direct eye contact is thought to modulate a cortical
      route eliciting social cognitive processes via activation of a fast subcortical
      pathway. This study aimed to examine functional brain connectivity during direct
      eye contact in women with posttraumatic stress disorder (PTSD) related to
      childhood abuse as compared with healthy controls. We conducted
      psychophysiological interaction (PPI) analyses in Statistical Parametric Mapping
      8 (SPM8) using the superior colliculus (SC) and locus coeruleus (LC) as seed
      regions while 16 healthy subjects and 16 patients with a primary diagnosis of
      PTSD related to childhood maltreatment viewed a functional magnetic resonance
      imaging (fMRI) paradigm involving direct (D) versus averted (A) gaze (happy, sad,
      neutral). The PTSD group showed a significantly enhanced connectivity between the
      SC and the anterior cingulate, and between the LC and the thalamus, caudate,
      putamen, insula, cingulate gyrus, and amygdala, as compared with healthy
      individuals. Symptom severity scores on the Clinician-Administered PTSD Scale
      (CAPS) showed significant positive correlations with superior colliculus
      connectivity with the perigenual and posterior cingulate, insula, and
      sublenticular extended amygdala. Functional connectivity data suggest increased
      recruitment of brain regions involved in emotion processing during direct gaze in
      PTSD in association with the fast subcortical pathway. The interpretation of eye
      contact as a signal of threat may require more emotion regulatory capacities in
      patients with PTSD. 

PMID- 25862530
TI  - Factors that influence reliability of the mouse clinical frailty index.

PMID- 25862531
TI  - Peripheral blood leukocyte telomere length and mortality among 64,637 individuals
      from the general population.
AB  - BACKGROUND: Short telomeres in peripheral blood leukocytes are associated with
      older age and age-related diseases. We tested the hypotheses that short telomeres
      are associated with both increased cancer mortality and all-cause mortality.
      METHODS: Individuals (n = 64637) were recruited from 1991 onwards from two Danish
      prospective cohort studies: the Copenhagen City Heart Study and the Copenhagen
      General Population Study. All had telomere length measured by quantitative
      polymerase chain reaction and the genotypes rs1317082 (TERC), rs7726159 (TERT),
      and rs2487999 (OBFC1) determined. The sum of telomere-shortening alleles from
      these three genotypes was calculated. We conducted Cox regression analyses and
      instrumental variable analyses using the allele sum as an instrument. All
      statistical tests were two-sided. RESULTS: Among 7607 individuals who died during
      follow-up (0-22 years, median = 7 years), 2420 had cancer and 2633 had
      cardiovascular disease as causes of death. Decreasing telomere length deciles
      were associated with increasing all-cause mortality (P(trend) = 2*10(-15)). The
      multivariable-adjusted hazard ratio of all-cause mortality was 1.40 (95%
      confidence interval [CI] = 1.25 to 1.57) for individuals in the shortest vs the
      longest decile. Results were similar for cancer mortality and cardiovascular
      mortality. Telomere length decreased 69 base pairs (95% CI = 61 to 76) per allele
      for the allele sum, and the per-allele hazard ratio for cancer mortality was 0.95
      (95% CI = 0.91 to 0.99). Allele sum was not associated with cardiovascular,
      other, or all-cause mortality. CONCLUSION: Short telomeres in peripheral blood
      leukocytes were associated with high mortality in association analyses. In
      contrast, genetically determined short telomeres were associated with low cancer
      mortality but not with all-cause mortality.

PMID- 25862532
TI  - Is a combination of magnetite and prions involved in the memory storage in the
      human brain?

PMID- 25862533
TI  - Measurement and analysis of patient attenuation correction factor during
      radioiodine therapy.
AB  - The calculated dose rate from the radioiodine therapy patient should normally
      include a factor accounting for the attenuation and scatter of patient body
      tissues. The attenuation factor is currently neglected, and not applied in
      operational radiation protection. Realistic estimation of radiation dose rate
      levels from radioiodine therapy patients when properly performed will reduce
      operational cost and optimise institutional radiation protection practice. In
      this work, the existence of a patient body tissue attenuation factor is verified
      by comparing the dose rates measured from the radioiodine capsules immediately
      before administration with those measured from the patient immediately after
      administration. The correlation between the factors suspected to influence the
      patient body tissue attenuation and the measured dose rates from the patient
      normalised per unit activity is statistically analysed. The calculated
      attenuation correction factor based on authors' measurements was (0.55 +/- 0.17).
      The measured dose rate per unit of radioactivity from the patient showed a
      negative correlation with their body mass index.

PMID- 25862534
TI  - Microdosimetry for a carbon ion beam using track-etched detectors.
AB  - Track-etched detectors (TED) have been used as linear energy transfer (LET)
      spectrometers in heavy ion beams for many years. LET spectra and depth-dose
      distribution of a carbon ion beam were measured behind polymethylmethacrylate
      degraders at Heavy Ion Medical Accelerator in Chiba, Japan. The measurements were
      performed along monoenergetic beam with energy 290 MeV u(-1) in different
      positions: (1) at beam extraction area, (2) at beginning, (3) maximum and (4)
      behind the Bragg peak region (0, 117, 147 and 151 mm of water-equivalent depth,
      respectively). The LET spectra inside and outside of the primary ion beam have
      been evaluated. TED record only heavy charged particles with LET above 8-10 keV
      um(-1), while electrons and ions with lower LET are not detected. The Geant4
      simulation toolkit version 4.9.6.P01 has been used to estimate the contribution
      of non-detected particles to absorbed dose. Presented results demonstrate the
      applicability of TED for microdosimetry measurements in therapeutic carbon ion
      beams. 

PMID- 25862535
TI  - Getting started with protocol for quality assurance of digital mammography in the
      clinical centre of Montenegro.
AB  - The purpose of this work is (i) to work out a test procedure for quality
      assurance (QA) in digital mammography with newly released test equipment,
      including the MagicMax mam multimeter (IBA, Germany) and the anthropomorphic
      tissue equivalent phantom Mammo AT (IBA, Germany), and (ii) to determine whether
      a first digital computer radiography (CR) system in Montenegro meets the current
      European standards. Tested parameters were tube output (uGy mAs(-1)) and output
      rate (mGy s(-1)), reproducibility and accuracy of tube voltage, half value layer,
      reproducibility and accuracy of the AEC system, exposure control steps, image
      receptor's response function, image quality and printer stability test. The
      evaluated dosimetric quantity is the average glandular dose (AGD) as evaluated
      from PMMA slabs simulating breast tissue. The main findings are that QA can be
      organised in Montenegro. (1) All measured parameters are within the range
      described in European protocols except the tube voltage which deviated more than
      +/- 1 kV. The automatic determination of the HVL was satisfactorily. AGD ranged
      from 0.66 to 7.02 mGy for PMMA thicknesses from 20 to 70 mm, and is in accordance
      with literature data. (2) The image quality score as obtained with the
      anthropomorphic tissue equivalent phantom Mammo AT for the CR system was similar
      to findings on the authors' conventional screen-film mammography. (3) In clinical
      practice the mammograms are printed. The CR reader produces images with a pixel
      size of 43.75 um, which is compatible with the laser printer (39 um laser spot
      spacing). The image processing algorithm embedded in the reader successfully
      processes mammograms with desirable image brightness and contrast in the printed
      image. The authors conclude that this first digital mammography system seems a
      good candidate for breast cancer screening applications.

PMID- 25862536
TI  - The European initiative on low-dose risk research: from the HLEG to MELODI.
AB  - The importance of low-dose risk research for radiation protection is now widely
      recognised. The European Commission (EC) and five European Union (EU) Member
      States involved in the Euratom Programme set up in 2008 a 'High Level and Expert
      Group on European Low Dose Risk Research' (HLEG) aimed at identifying research
      needs and proposing a better integration of European efforts in the field. The
      HLEG revised the research challenges and proposed a European research strategy
      based on a 'Multidisciplinary European LOw Dose Initiative' (MELODI). In April
      2009, five national organisations, with the support of the EC, created the
      initial core of MELODI (http://www.melodi-online.eu) with a view to integrate the
      EU institutions with significant programmes in the field, while being open to
      other scientific organisations and stakeholders, and to develop an agreed
      strategic research agenda (SRA) and roadmap. Since then, open workshops have been
      organised yearly, exploring ideas for SRA implementation. As of October 2014, 31
      institutions have been included as members of MELODI. HLEG recommendations and
      MELODI SRA have become important reference points in the radiation protection
      part of the Euratom Research Programme. MELODI has established close interactions
      through Memorandum of Understanding with other European platforms involved in
      radiation protection (Alliance, NERIS and EURADOS) and, together with EURADOS,
      with the relevant medical European Associations. The role of Joint Programming in
      priority setting, foreseen in the forthcoming EU Horizon 2020, calls for keeping
      MELODI an open, inclusive and transparent initiative, able to avoid redundancies
      and possible conflicts of interest, while promoting common initiatives in
      radiation protection research. An important issue is the establishment of a
      proper methodology for managing these initiatives, and this includes the set-up
      of an independent MELODI Scientific Committee recently extended to Alliance,
      NERIS and EURADOS, with the aim of identifying research priorities to suggest for
      the forthcoming Euratom research calls. 

PMID- 25862537
TI  - Patient doses from hybrid SPECT-CT procedures.
AB  - The aim of this work is to estimate patient doses from hybrid single-photon
      emission computed tomography (SPECT) and computed tomography (CT) procedures. The
      study involved all four SPECT-CT systems in Bulgaria. Effective dose was
      estimated for about 100 patients per system. Ten types of examinations were
      considered, representing all diagnostic procedures performed in the SPECT-CT
      systems. Effective doses from the SPECT component were calculated applying the
      ICRP 53 and ICRP 80 conversion coefficients. Computed tomography dose index and
      dose length product were retrospectively obtained from the archives of the
      systems, and effective doses from the CT component were calculated with CT-Expo
      software. Parallel estimation of CT component contribution with the National
      Radiological Protection Board (NRPB) conversion coefficients was performed where
      applicable. Large variations were found in the current practice of SPECT-CT
      imaging. Optimisation actions and diagnostic reference levels were proposed. 

PMID- 25862538
TI  - Russian practical guidance on radiological support for justification of X-ray and
      nuclear medicine examinations.
AB  - An important part of the justification process is assessment of the radiation
      risks caused by exposure of a patient during examination. The authors developed
      official national methodology both for medical doctors and sanitary inspectors
      called 'assessment of radiation risks of patients undergoing diagnostic
      examinations with the use of ionizing radiation'. The document addresses patients
      of various age groups and a wide spectrum of modern X-ray and nuclear medicine
      examinations. International scale of risk categorisation was implemented by the
      use of effective dose with account for age dependence of radiation risk. The
      survey of effective doses in radiology, including CT, mammography, and
      intervention radiology, and nuclear medicine, including single-photon emission
      tomography and positron emission tomography, for patients of various age groups
      from several regions of Russia was used for the risk assessment. The output of
      the methodology is a series of tables for each diagnostic technology with lists
      of examinations for three age groups (children/adolescents, adults and seniors)
      corresponding to various radiation risk categories. 

PMID- 25862539
TI  - A psychometric investigation of "macroscopic" speech measures for clinical and
      psychological science.
AB  - The analysis of vocal expression is a critical endeavor for psychological and
      clinical sciences and is an increasingly popular application for computer-human
      interfaces. Despite this, and despite advances in the efficiency, affordability,
      and sophistication of vocal analytic technologies, there is considerable
      variability across studies regarding what aspects of vocal expression are
      studied. Vocal signals can be quantified in a myriad of ways, and their
      underlying structure, at least with respect to "macroscopic" measures from
      extended speech, is presently unclear. To address this issue, we evaluated the
      psychometric properties-notably, the structural and construct validity-of a
      systematically defined set of global vocal features. Our analytic strategy
      focused on (a) identifying redundant variables among this set, (b) employing
      principal components analysis (PCA) to identify nonoverlapping domains of vocal
      expression, (c) examining the degrees to which the vocal variables are modulated
      as a function of changes in speech task, and (d) evaluating the relationship
      between the vocal variables and cognitive (i.e., verbal fluency) and clinical
      (i.e., depression, anxiety, and hostility) variables. Spontaneous speech samples
      from 11 independent studies of young adults (>60 s in length), employing one of
      three different speaking tasks, were examined (N = 1,350). Confounding variables
      (i.e., sex, ethnicity) were statistically controlled for. The PCA identified six
      distinct domains of vocal expression. Collectively, vocal expression (defined in
      terms of these domains) was modulated as a function of speech task and was
      related to the cognitive and clinical variables. These findings provide
      empirically grounded implications for the study of vocal expression in
      psychological and clinical sciences. 

PMID- 25862540
TI  - Acute administration of single oral dose of grape seed polyphenols restores blood
      pressure in a rat model of metabolic syndrome: role of nitric oxide and
      prostacyclin.
AB  - PURPOSE: The aims of this study were to evaluate the antihypertensive
      effectiveness of different doses of grape seed polyphenols in cafeteria diet-fed
      hypertensive rats (CHRs) and to establish the mechanism involved in the blood
      pressure (BP) lowering effect of these compounds in this experimental model of
      metabolic syndrome (MS). METHODS: Male 8-week-old Wistar rats were fed cafeteria
      or standard (ST) diet for 10 weeks. After this, the antihypertensive effect of a
      single oral administration of a polyphenol grape seed extract (GSPE) was tested
      at different doses (250, 375 and 500 mg/kg) in CHRs. BP was recorded before and
      2, 4, 6, 8, 24 and 48 h post-administration. The hypotensive effect of GSPE was
      also proved in ST diet-fed rats. Additionally, in other experiment, CHRs were
      orally administered 375 mg/kg GSPE. Four hours post-administration, the rats were
      intraperitoneally administrated 30 mg/kg NG-nitro-L-arginine methyl ester (L
      NAME) or 5 mg/kg indomethacin [inhibitors of nitric oxide (NO) and prostacyclin
      synthesis, respectively]. BP was recorded initially and 6 h post-administration.
      RESULTS: GSPE produced a decrease in SBP and DBP, the most effective dose (375
      mg/kg) showing an antihypertensive effect in CHRs similar to the drug captopril,
      and did not affect BP of ST diet-fed rats. The antihypertensive effect was
      completely abolished by L-NAME and partially inhibited by indomethacin.
      CONCLUSIONS: GSPE acts as an antihypertensive agent in a rat model of
      hypertension associated with MS. The change in endothelium-derived NO
      availability is one of the mechanisms involved in the antihypertensive effect of
      GSPE in CHRs. Additionally, endothelial prostacyclin contributes to the effect of
      GSPE on arterial BP.

PMID- 25862541
TI  - Domains of Pyrococcus furiosus L-asparaginase fold sequentially and assemble
      through strong intersubunit associative forces.
AB  - Here, we report the folding and assembly of a Pyrococcus furiosus-derived
      protein, L-asparaginase (PfA). PfA functions as a homodimer, with each monomer
      made of distinct N- and C-terminal domains. The purified individual domains as
      well as single Trp mutant of each domain were subjected to chemical
      denaturation/renaturation and probed by combination of spectroscopic,
      chromatographic, quenching and scattering techniques. We found that the N-domain
      acts like a folding scaffold and assists the folding of remaining polypeptide.
      The domains displayed sequential folding with the N-domain having higher
      thermodynamic stability. We report that the extreme thermal stability of PfA is
      due to the presence of high intersubunit associative forces supported by
      extensive H-bonding and ionic interactions network. Our results proved that
      folding cooperativity in a thermophilic, multisubunit protein is dictated by
      concomitant folding and association of constituent domains directly into a native
      quaternary structure. This report gives an account of the factors responsible for
      folding and stability of a therapeutically and industrially important protein.

PMID- 25862542
TI  - Detection and cultivation of circulating tumor cells in gastric cancer.
AB  - Circulating tumor cells (CTCs) are important targets for treatment and critical
      surrogate markers when evaluating cancer prognosis and therapeutic response. A
      sensitive methodology for detecting CTCs in gastric cancer (GC) patients is
      needed. In this study we demonstrate a device for enrichment and cultivation of
      CTCs. In total, 22 patients with GC, all candidates for surgery, were enrolled in
      the study. Peripheral blood samples were collected before surgery, and patients
      were re-evaluated within operation and divided into two groups: resectable and
      non-resectable GC. A new size-based separation test for enrichment and
      cultivation of CTCs was used (MetaCell((r))). In addition to cytomorphological
      analysis, gene expression of tumor associated genes (Cytokeratin-18, Cytokeratin
      19, Cytokeratin-20, Cytokeratin-7, EPCAM, MUC1, HER2, EGFR) and of leukocyte
      markers (e.g. CD45, CD68) was tested in enriched CTC fractions. CTCs were
      detected in 59 % of the patients studied (n = 13/22). CTCs were detected in seven
      patients of the resection group (7/10, 70 %) and six of the non-resectable group
      (6/12, 50 %). Enrichment of the viable CTCs allowed subsequent successful
      cultivation in vitro. The cytomorphological characterization of the CTCs was a
      prerequisite of random gene expression testing in CTC-positive samples. In CTC
      positive samples gene expression of cytokeratin 18 and 19 was elevated in
      comparison to the whole blood gene expression analysis. CTCs were found to be
      present in both resectable and non-resectable gastric cancer patients. The size
      based separation platform for CTCs may be used for in vitro cultivation, as well
      as in subsequent molecular analysis if desired. The sensitivity of CTC-detection
      could be enhanced by the combination of cytomorphological and molecular analysis.

PMID- 25862543
TI  - Health care access and smoking cessation among cancer survivors: implications for
      the Affordable Care Act and survivorship care.
AB  - PURPOSE: The study objectives are to examine prevalence of current smoking, and
      to assess the association of both health insurance (HI) and access to care with
      smoking cessation among cancer survivors. METHODS: We performed an analysis from
      a cross-sectional study of cancer survivors aged 18-64 years using nationally
      representative data from the 2009 Behavioral Risk Factor Surveillance System
      survey. We assessed the prevalence of current smoking among cancer survivors.
      Also, in a subset excluding never smokers, we assessed cessation status of cancer
      survivors operationalized as comparing current to former smokers. RESULTS: The
      study population (N = 18,896) was predominantly 45-64 years of age, female, and
      white. The prevalence of current smoking was substantially greater among cancer
      survivors without HI (40.9 %) than for those with HI (19.5 %). Cancer survivors
      with no HI had 2-fold greater adjusted odds of not quitting cigarette smoking
      compared to those with HI. Among those with insurance, cancer survivors who did
      not have regular health care provider or could not see doctor due to cost or had
      their last routine checkup >=1 year ago had 60-80 % fold greater adjusted odds of
      not quitting cigarette smoking compared to cancer survivors who had better access
      to health care. CONCLUSIONS: Cancer survivors without HI have substantially
      greater current smoking rates compared with those with HI. Among cancer survivors
      with HI, those who experienced health care access-related problems had lower
      cessation rates than their counterparts. IMPLICATIONS FOR CANCER SURVIVORS:
      Smoking cessation needs to be recognized as a crucial component of preventive
      care for cancer survivors. Continuous patient engagement and cancer-patient
      centered strategies are urgently needed to achieve optimal results for quit rates
      particularly for young cancer survivors who are most susceptible to current
      smoking.

PMID- 25862544
TI  - Mind-set interventions are a scalable treatment for academic underachievement.
AB  - The efficacy of academic-mind-set interventions has been demonstrated by small
      scale, proof-of-concept interventions, generally delivered in person in one
      school at a time. Whether this approach could be a practical way to raise school
      achievement on a large scale remains unknown. We therefore delivered brief growth
      mind-set and sense-of-purpose interventions through online modules to 1,594
      students in 13 geographically diverse high schools. Both interventions were
      intended to help students persist when they experienced academic difficulty;
      thus, both were predicted to be most beneficial for poorly performing students.
      This was the case. Among students at risk of dropping out of high school (one
      third of the sample), each intervention raised students' semester grade point
      averages in core academic courses and increased the rate at which students
      performed satisfactorily in core courses by 6.4 percentage points. We discuss
      implications for the pipeline from theory to practice and for education reform. 

PMID- 25862545
TI  - Grasp posture alters visual processing biases near the hands.
AB  - Observers experience biases in visual processing for objects within easy reach of
      their hands; these biases may assist them in evaluating items that are candidates
      for action. I investigated the hypothesis that hand postures that afford
      different types of actions differentially bias vision. Across three experiments,
      participants performed global-motion-detection and global-form-perception tasks
      while their hands were positioned (a) near the display in a posture affording a
      power grasp, (b) near the display in a posture affording a precision grasp, or
      (c) in their laps. Although the power-grasp posture facilitated performance on
      the motion-detection task, the precision-grasp posture instead facilitated
      performance on the form-perception task. These results suggest that the visual
      system weights processing on the basis of an observer's current affordances for
      specific actions: Fast and forceful power grasps enhance temporal sensitivity,
      whereas detail-oriented precision grasps enhance spatial sensitivity. 

PMID- 25862547
TI  - Impact of CT in elderly patients presenting to the emergency department with
      acute abdominal pain.
AB  - PURPOSE: The purpose of the study was to document the clinical impact of CT in
      elderly patients presenting to the emergency department (ED) with abdominal pain.
      METHODS: This retrospective IRB-approved study from 2006 to 2013 evaluated 464
      patients >=80 years (mean 89 years, range 80-100: M150, W314), who presented to
      the ED with acute abdominal symptoms and underwent CT. CTs were divided into
      those negative and positive for actionable findings, defined as potentially
      requiring a change in surgical or medical management. Physician diagnosis,
      treatment plan, and disposition before and after CT were reviewed in the
      electronic medical record to assess CT influence on management and disposition.
      CT diagnosis was confirmed with final clinical diagnosis, surgical intervention,
      pathology, and follow-up. Descriptive statistics were used. RESULTS: CTs were
      positive in 55%. The most common diagnoses were SBO (18%), diverticulitis (9%),
      non-ischemic vascular-related emergency (6%), bowel ischemia (4%), appendicitis
      (3%), and colonic obstruction (2%). These diagnoses were clinically unsuspected
      prior to CT in 43% (p < 0.05), with significant difficultly in diagnosing SBO (p
      < 0.05), diverticulitis (p < 0.01), and colonic obstruction (p < 0.01). Positive
      CT results influenced treatment plans in 65%, surgical in 48%, and medical in
      52%. Disposition from the ED was significantly affected by CT (p < 0.001), 65% of
      admissions with positive CT (p < 0.001) and 63% of discharges with negative CT (p
      < 0.001). CONCLUSION: Utilization of abdominopelvic CT in geriatric patients
      presenting to the ED with acute abdominal symptoms strongly influences clinical
      management and significantly affects disposition. As the US population ages, the
      clinical impact of emergent CT in the elderly will intensify.

PMID- 25862546
TI  - Over-the-Counter Relief From Pains and Pleasures Alike: Acetaminophen Blunts
      Evaluation Sensitivity to Both Negative and Positive Stimuli.
AB  - Acetaminophen, an effective and popular over-the-counter pain reliever (e.g., the
      active ingredient in Tylenol), has recently been shown to blunt individuals'
      reactivity to a range of negative stimuli in addition to physical pain. Because
      accumulating research has shown that individuals' reactivity to both negative and
      positive stimuli can be influenced by a single factor (an idea known as
      differential susceptibility), we conducted two experiments testing whether
      acetaminophen blunted individuals' evaluations of and emotional reactions to both
      negative and positive images from the International Affective Picture System.
      Participants who took acetaminophen evaluated unpleasant stimuli less negatively
      and pleasant stimuli less positively, compared with participants who took a
      placebo. Participants in the acetaminophen condition also rated both negative and
      positive stimuli as less emotionally arousing than did participants in the
      placebo condition (Studies 1 and 2), whereas nonevaluative ratings (extent of
      color saturation in each image; Study 2) were not affected by drug condition.
      These findings suggest that acetaminophen has a general blunting effect on
      individuals' evaluative and emotional processing, irrespective of negative or
      positive valence. 

PMID- 25862548
TI  - Variable color Doppler sonographic appearances of retained products of
      conception: radiologic-pathologic correlation.
AB  - OBJECT OF STUDY: Retained products of conception (RPOC) displays variable
      vascularity, ranging from avascular to markedly vascular on color Doppler
      sonography. We hypothesize that variability in sonographic vascularity may be due
      to histopathologic variation in the placental tissue. MATERIALS, METHODS, AND
      PROCEDURES: After institutional review board approval, sonographic images and
      pathologic specimens were retrospectively reviewed in 26 patients with
      pathologically proven RPOC. Ultrasound (US) images were scored 0-3 for the degree
      of vascularity by two radiologists blinded to the diagnosis. Corresponding
      pathologic specimens were evaluated for vascularization of chorionic villi,
      degree of inflammation, morphology of maternal arteries, chorionic villous
      preservation, and percentage of clot, membranes, chorionic villi, and
      decidua/myometrium. Statistical analysis, including multiple linear regression,
      was performed. RESULTS: RPOC with histologically avascular chorionic villi or
      those with markedly reduced vascularization had significantly lower US
      vascularity scores (p = 0.030) than those with chorionic villi showing normal or
      decreased vascularization. Sonographically avascular RPOC had a significantly
      lower percentage villi (p = 0.028) and higher percentage of decidua (p = 0.004)
      than specimens where US showed any Doppler vascularity. Histologic vascularity of
      villi (p = 0.049) and non-observation of maternal arteries (p = 0.001) were
      significant predictors of US vascularity scores in multivariate linear regression
      analysis, while inflammation of villi (p = 0.053) was a marginally significant
      predictor. SIGNIFICANCE OF THE CONCLUSIONS: Histologic vascularity of villi
      appears to contribute to the observed variation in sonographic vascularity. This
      finding may underlie known differences in clinical outcomes between sonographic
      vascularity groups.

PMID- 25862549
TI  - Religiosity/spirituality: Relationships with non-suicidal self-harm behaviors and
      attempted suicide.
AB  - BACKGROUND: The relationships between religiosity/spirituality (RS) and self-harm
      behavior, including non-suicidal self-harm behavior (NS-SHB) and suicide
      attempts/completions, remain of keen interest. Whereas the majority of studies
      strongly suggest that RS protects against suicide attempts/completions,
      relationships between RS and NS-SHB have been rarely studied. AIM: In this study,
      we examined RS in relationship to both NS-SHB (six explicit behaviors) and past
      history of suicide attempts. METHOD: In a cross-sectional sample of 306
      consecutive primary care outpatients, we administered four self-report
      assessments for RS (extent participant considered self a religious person, extent
      participant considered self a spiritual person, extent religion is involved in
      understanding/dealing with stressful situations, Functional Assessment of Chronic
      Illness Therapy-Spiritual Well-Being Scale (FACIT-Sp-12)) as well as examined
      seven items on the Self-Harm Inventory: six items reflecting NS-SHB and one item
      reflecting a past suicide attempt. RESULTS: While two RS items yielded no
      significant findings (extent participant considered self a spiritual person,
      extent religion is involved in understanding/dealing with stressful situations),
      the remaining two items were associated with a lowered risk of self-harm
      behavior, particularly the FACIT-Sp-12. CONCLUSIONS: Some but not all aspects of
      RS are associated with lowered risk for self-harm. In this study, considering
      oneself a religious person and reporting a general sense of RS well-being offered
      the most protective effect to participants, particularly the latter.

PMID- 25862550
TI  - Alterations in mitochondrial number and function in Alzheimer's disease
      fibroblasts.
AB  - Mitochondrial dysfunction is observed in brains of Alzheimer's Disease patients
      as well as many rodent model systems including those modeling mutations in
      preseinilin 1 (PSEN1). The aim of our study was to characterize mitochondrial
      function and number in fibroblasts from AD patients with PSEN1 mutations. We used
      biochemical assays, metabolic profiling and fluorescent labeling to assess
      mitochondrial number and function in fibroblasts from three AD patients compared
      to fibroblasts from three controls. The mutant AD fibroblasts had increased
      Abeta42 relative to controls along with reduction in ATP, basal and maximal
      mitochondrial respiration as well as impaired spare mitochondrial respiratory
      capacity. Fluorescent staining and expression of genes encoding electron
      transport chain enzymes showed diminished mitochondrial content in the AD
      fibroblasts. This study demonstrates that mitochondrial dysfunction is observable
      in AD fibroblasts and provides evidence that this model system could be useful as
      a tool to screen disease-modifying compounds. 

PMID- 25862552
TI  - Can genomic medicine improve financial sustainability of health systems?
AB  - Recent years have seen increased use of genomic technologies in a variety of
      research and clinical settings. Genomic medicine is not a cost-containment
      measure per se, but is viewed as having the potential to bend the healthcare cost
      curve. Currently, it is unknown how systematic adoption of genomic medicine in
      clinical practice will impact healthcare costs. This article discusses the
      potential economic impact of genomic medicine and the challenges that lie ahead. 

PMID- 25862551
TI  - MicroRNA involvement in a metastatic non-functioning pituitary carcinoma.
AB  - PURPOSE: Pituitary carcinomas are extremely rare neoplasms, and molecular events
      leading to malignant pituitary transformation are largely unknown. Enhanced
      understanding of molecular mechanisms driving malignant pituitary progression
      would be beneficial for pituitary carcinoma diagnosis and treatment. METHODS:
      Differential microRNA expression in paired primary and metastatic pituitary
      carcinoma specimens were detected using high-throughput human microRNA
      microarrays and TaqMan microRNA arrays. Three of significantly deregulated miRNAs
      were further confirmed using quantitative real-time PCR in the metastatic
      carcinoma, six atypical pituitary adenomas and eight typical pituitary adenomas.
      Target genes of microRNAs were bioinformatically predicated and verified in vitro
      by Western blotting and real-time PCR and in vivo by immunohistochemistry
      respectively. RESULTS: We present a case of a 50-year-old woman harboring non
      functioning pituitary carcinoma with multiple intracranial metastases, and
      identified up-regulation of miR-20a, miR-106b and miR-17-5p in the metastatic
      carcinoma as compared to the primary neoplasm. Furthermore, miR-20a and miR-17-5p
      were increased in the metastatic carcinoma and six atypical pituitary adenomas as
      compared to eight typical pituitary adenomas as measured by quantitative real
      time PCR. Both PTEN and TIMP2 were bioinformatically predicated and confirmed in
      vitro as target genes of these three microRNAs. As semi-quantified by
      immunohistochemistry, PTEN was absent and TIMP2 was decreased in the metastatic
      pituitary carcinoma as compared to pituitary adenomas. CONCLUSIONS: Our results
      suggest microRNA involvement in malignant pituitary progression, whereby
      increased miR-20a, miR-106b and miR-17-5p promote metastasis by attenuating PTEN
      and TIMP2 in pituitary carcinoma.

PMID- 25862553
TI  - Dispersal and spatial heterogeneity: single species.
AB  - A recent result for a reaction-diffusion equation is that a population diffusing
      at any rate in an environment in which resources vary spatially will reach a
      higher total equilibrium biomass than the population in an environment in which
      the same total resources are distributed homogeneously. This has so far been
      proven by Lou for the case in which the reaction term has only one parameter,
      m(x), varying with spatial location x, which serves as both the intrinsic growth
      rate coefficient and carrying capacity of the population. However, this striking
      result seems rather limited when applies to real populations. In order to make
      the model more relevant for ecologists, we consider a logistic reaction term,
      with two parameters, r (x) for intrinsic growth rate, and K(x) for carrying
      capacity. When r (x) and K(x) are proportional, the logistic equation takes a
      particularly simple form, and the earlier result still holds. In this paper we
      have established the result for the more general case of a positive correlation
      between r (x) and K(x) when dispersal rate is small. We review natural and
      laboratory systems to which these results are relevant and discuss the
      implications of the results to population theory and conservation ecology.

PMID- 25862554
TI  - Treatment of Elderly Patients With Non-Small-Cell Lung Cancer: Results of an
      International Expert Panel Meeting of the Italian Association of Thoracic
      Oncology.
AB  - Most patients with non-small-cell lung cancer (NSCLC) are elderly, and age has
      important implications for their management and treatment. In May 2014, the
      Italian Association of Thoracic Oncology organized an International Experts Panel
      Meeting with the intent to review the available evidence regarding the treatment
      of elderly patients with NSCLC and to discuss the implications for clinical
      practice and future research in this field; this article summarizes the
      panelists' conclusions. All patients aged more than 70 years should receive an
      assessment of physiologic age, including mortality and toxicity prediction. Age
      itself does not contraindicate adjuvant chemotherapy after resection. Elderly
      patients with locally advanced NSCLC should be considered for combined chemo
      radiotherapy. In the advanced setting, the combination of carboplatin/paclitaxel
      results in prolonged survival compared with single-agent gemcitabine or
      vinorelbine, albeit with increased toxicity. In fit selected patients, other
      carboplatin-based or cisplatin-based regimens are feasible, but randomized trials
      specifically showing survival prolongation in elderly patients are lacking. The
      survival benefit for bevacizumab added to chemotherapy seems limited to patients
      aged less than 75 years. In unfit elderly patients, single agents are
      recommended. Regardless of age, patients with advanced nonsquamous NSCLC, and
      those who have never smoked independently of their histologic subtype, should be
      tested for epidermal growth factor receptor (EGFR) mutation and anaplastic
      lymphoma kinase (ALK) rearrangement. In patients with NSCLC harboring EGFR
      mutation or ALK rearrangement, targeted drugs are feasible and well tolerated. 

PMID- 25862555
TI  - Immunohistochemistry and in situ hybridization for the diagnosis and
      classification of squamous lesions of the anogenital region.
AB  - Distinguishing anogenital squamous intraepithelial lesions from benign conditions
      and mimics may be problematic. Immunohistochemistry for surrogate markers of HPV
      infection, such as Ki-67, p16, and ProExTM C, may aid the diagnosis in equivocal
      cases. The main diagnostic pitfall in the diagnosis of LSIL is the occurrence of
      "pseudokoilocytes" in benign squamous mucosa, which may lead to overdiagnosis.
      When interpreted correctly, Ki-67 is a sensitive and specific marker for
      dysplasia in mature squamous epithelium and is therefore useful for confirmation
      of LSIL and condyloma. A Ki-67 positive result is defined as the presence of a
      cluster of at least two strongly stained epithelial nuclei in the upper two
      thirds of the epithelial thickness. With such a definition, there is almost
      complete concordance between consensus diagnosis of LSIL/condyloma confirmed by
      detection of HPV DNA and positive Ki-67. A related proliferation marker, ProExTM
      C, has similar staining patterns and utility for the diagnosis of low grade
      dysplasia. The differential diagnosis of HSIL includes atypical immature squamous
      metaplasia and atrophy. A marker with high sensitivity and specificity for the
      detection of HSIL in cervical, vulvar, and anal mucosa is p16. A 2-tier scoring
      system is used to evaluate p16 staining. No staining or a discontinuous, patchy
      nuclear and cytoplasmic staining pattern is considered as a negative result. A
      positive result is defined as diffuse and strong staining of cells of the basal
      and parabasal layers of the squamous epithelium, with or without staining of
      superficial cell layers. New markers that are undergoing evaluation for their
      clinical utility include stathmin-1, phosphorylated S6, and SOX2. Confirmation of
      the diagnosis of dysplasia by HPV detection in tissue sections using HPV capsid
      protein immunohistochemistry, HPV DNA or HPV RNA in situ hybridization offers
      lower sensitivity as compared to immunohistochemistry for surrogate markers and
      therefore has more limited utility in this context. 

PMID- 25862556
TI  - Erratum to: A placebo-controlled, double-blind, randomized, multicenter study to
      assess the effects of dronedarone 400 mg twice daily for 12 weeks on atrial
      fibrillation burden in subjects with permanent pacemakers.

PMID- 25862557
TI  - Non-randomised comparison of acute and long-term outcomes of robotic versus
      manual ventricular tachycardia ablation in a single centre ischemic cohort.
AB  - INTRODUCTION: Robotically guided radiofrequency (RF) ablation offers greater
      catheter stability that may improve lesion depth. We performed a non-randomised
      comparison of patients undergoing ventricular tachycardia (VT) ablation either
      manually or robotically using the Hansen Sensei system for recurrent implantable
      defibrillator (ICD) therapy. METHODS: Patients with infarct-related scar
      underwent VT ablation using the Hansen system to assess feasibility compared with
      patients undergoing manual VT ablation during a similar time period. Power
      delivery during robotic ablation was restricted to 30 W at 60 s. VT inducibility
      was checked at the end of the procedure. Pre-ablation ICD therapy burdens over 6
      months were compared with post-ablation therapy averaged to a 6-month period.
      RESULTS: Twelve consecutive patients who underwent robotic VT ablation were
      compared to 12 consecutive patients undergoing a manual ablation. Patient
      demographics and comorbidities were similar in the two groups. A higher
      proportion of robotic cases were urgent (9/12 (75%)) vs. manual (4/12 (33%)) (p =
      0.1). Post-ablation VT stimulation did not induce clinical VT in 11/12 (92%) in
      each group. There were no peri-procedural complications related to ablation
      delivery. Patients were followed up for approximately 2 years. Averaged over 6
      months, robotic ICD therapy burdens fell from 32 (5-400) events to 2.5 (0-11) (p
      = 0.015). Therapy burden fell from 14 (10-25) to 1 (0-5) (p = 0.023) in the
      manual group. There was no difference in long-term outcome (p = 0.60) and
      mortality (4/12 (33%), p = 1.0). CONCLUSION: Robotically guided VT ablation is
      both feasible and safe when compared to manual ablation with good acute and long
      term outcomes.

PMID- 25862558
TI  - Ischemic necrosis of the left atrial appendage at autopsy 4 weeks following
      epicardial suture ligation via a sub-xiphoid approach (LARIAT).

PMID- 25862559
TI  - Myeloma cell-derived Runx2 promotes myeloma progression in bone.
AB  - The progression of multiple myeloma (MM) is governed by a network of molecular
      signals, the majority of which remain to be identified. Recent studies suggest
      that Runt-related transcription factor 2 (Runx2), a well-known bone-specific
      transcription factor, is also expressed in solid tumors, where expression
      promotes both bone metastasis and osteolysis. However, the function of Runx2 in
      MM remains unknown. The current study demonstrated that (1) Runx2 expression in
      primary human MM cells is significantly greater than in plasma cells from healthy
      donors and patients with monoclonal gammopathy of undetermined significance; (2)
      high levels of Runx2 expression in MM cells are associated with a high-risk
      population of MM patients; and (3) overexpression of Runx2 in MM cells enhanced
      tumor growth and disease progression in vivo. Additional studies demonstrated
      that MM cell-derived Runx2 promotes tumor progression through a mechanism
      involving the upregulation of Akt/beta-catenin/Survivin signaling and enhanced
      expression of multiple metastatic genes/proteins, as well as the induction of a
      bone-resident cell-like phenotype in MM cells. Thus, Runx2 expression supports
      the aggressive phenotype of MM and is correlated with poor prognosis. These data
      implicate Runx2 expression as a major regulator of MM progression in bone and
      myeloma bone disease. 

PMID- 25862560
TI  - Eosinophil-specific deletion of IkappaBalpha in mice reveals a critical role of
      NF-kappaB-induced Bcl-xL for inhibition of apoptosis.
AB  - Eosinophils are associated with type 2 immune responses to allergens and
      helminths. They release various proinflammatory mediators and toxic proteins on
      activation and are therefore considered proinflammatory effector cells.
      Eosinophilia is promoted by the cytokines interleukin (IL)-3, IL-5, and
      granulocyte macrophage-colony-stimulating factor (GM-CSF) and can result from
      enhanced de novo production or reduced apoptosis. In this study, we show that
      only IL-5 induces differentiation of eosinophils from bone marrow precursors,
      whereas IL-5, GM-CSF, and to a lesser extent IL-3 promote survival of mature
      eosinophils. The receptors for these cytokines use the common beta chain, which
      serves as the main signaling unit linked to signal transducer and activator of
      transcription 5, p38 mitogen-activated protein kinase, and nuclear factor (NF)
      kappaB pathways. Inhibition of NF-kappaB induced apoptosis of in vitro cultured
      eosinophils. Selective deletion of IkappaBalpha in vivo resulted in enhanced
      expression of Bcl-xL and reduced apoptosis during helminth infection. Retroviral
      overexpression of Bcl-xL promoted survival, whereas pharmacologic inhibition of
      Bcl-xL in murine or human eosinophils induced rapid apoptosis. These results
      suggest that therapeutic strategies targeting Bcl-xL in eosinophils could improve
      health conditions in allergic inflammatory diseases. 

PMID- 25862561
TI  - IgH-V(D)J NGS-MRD measurement pre- and early post-allotransplant defines very low
      and very high-risk ALL patients.
AB  - Positive detection of minimal residual disease (MRD) by multichannel flow
      cytometry (MFC) prior to hematopoietic cell transplantation (HCT) of patients
      with acute lymphoblastic leukemia (ALL) identifies patients at high risk for
      relapse, but many pre-HCT MFC-MRD negative patients also relapse, and the
      predictive power MFC-MRD early post-HCT is poor. To test whether the increased
      sensitivity of next-generation sequencing (NGS)-MRD better identifies pre- and
      post-HCT relapse risk, we performed immunoglobulin heavy chain (IgH) variable,
      diversity, and joining (V[D]J) DNA sequences J NGS-MRD on 56 patients with B-cell
      ALL enrolled in Children's Oncology Group trial ASCT0431. NGS-MRD predicted
      relapse and survival more accurately than MFC-MRD (P < .0001), especially in the
      MRD negative cohort (relapse, 0% vs 16%; P = .02; 2-year overall survival, 96% vs
      77%; P = .003). Post-HCT NGS-MRD detection was better at predicting relapse than
      MFC-MRD (P < .0001), especially early after HCT (day 30 MFC-MRD positive relapse
      rate, 35%; NGS-MRD positive relapse rate, 67%; P = .004). Any post-HCT NGS
      positivity resulted in an increase in relapse risk by multivariate analysis
      (hazard ratio, 7.7; P = .05). Absence of detectable IgH-V(D)J NGS-MRD pre-HCT
      defines good-risk patients potentially eligible for less intense treatment
      approaches. Post-HCT NGS-MRD is highly predictive of relapse and survival,
      suggesting a role for this technique in defining patients early who would be
      eligible for post-HCT interventions. The trial was registered at
      www.clinicaltrials.gov as #NCT00382109. 

PMID- 25862562
TI  - Modified Ham test for atypical hemolytic uremic syndrome.
AB  - Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy (TMA)
      characterized by excessive activation of the alternative pathway of complement
      (APC). Atypical HUS is frequently a diagnosis of exclusion. Differentiating aHUS
      from other TMAs, especially thrombotic thrombocytopenic purpura (TTP), is
      difficult due to overlapping clinical manifestations. We sought to develop a
      novel assay to distinguish aHUS from other TMAs based on the hypothesis that
      paroxysmal nocturnal hemoglobinuria cells are more sensitive to APC-activated
      serum due to deficiency of glycosylphosphatidylinositol- anchored complement
      regulatory proteins (GPI-AP). Here, we demonstrate that phosphatidylinositol
      specific phospholipase C-treated EA.hy926 cells and PIGA-mutant TF-1 cells are
      more susceptible to serum from aHUS patients than parental EA.hy926 and TF-1
      cells. We next studied 31 samples from 25 patients with TMAs, including 9 with
      aHUS and 12 with TTP. Increased C5b-9 deposition was evident by confocal
      microscopy and flow cytometry on GPI-AP-deficient cells incubated with aHUS serum
      compared with heat-inactivated control, TTP, and normal serum. Differences in
      cell viability were observed in biochemically GPI-AP-deficient cells and were
      further increased in PIGA-deficient cells. Serum from patients with aHUS resulted
      in a significant increase of nonviable PIGA-deficient TF-1 cells compared with
      serum from healthy controls (P < .001) and other TMAs (P < .001). The cell
      viability assay showed high reproducibility, sensitivity, and specificity in
      detecting aHUS. In conclusion, we developed a simple, rapid, and serum-based
      assay that helps to differentiate aHUS from other TMAs. 

PMID- 25862563
TI  - The neural correlates of correctly rejecting lures during memory retrieval: the
      role of item relatedness.
AB  - Successful memory retrieval is predicated not only on recognizing old
      information, but also on correctly rejecting new information (lures) in order to
      avoid false memories. Correctly rejecting lures is more difficult when they are
      perceptually or semantically related to information presented at study as
      compared to when lures are distinct from previously studied information. This
      behavioral difference suggests that the cognitive and neural basis of correct
      rejections differs with respect to the relatedness between lures and studied
      items. The present study sought to identify neural activity that aids in
      suppressing false memories by examining the network of brain regions underlying
      correct rejection of related and unrelated lures. Results showed neural overlap
      in the right hippocampus and anterior parahippocampal gyrus associated with both
      related and unrelated correct rejections, indicating that some neural regions
      support correctly rejecting lures regardless of their semantic/perceptual
      characteristics. Direct comparisons between related and unrelated correct
      rejections showed that unrelated correct rejections were associated with greater
      activity in bilateral middle and inferior temporal cortices, regions that have
      been associated with categorical processing and semantic labels. Related correct
      rejections showed greater activation in visual and lateral prefrontal cortices,
      which have been associated with perceptual processing and retrieval monitoring.
      Thus, while related and unrelated correct rejections show some common neural
      correlates, related correct rejections are driven by greater perceptual
      processing whereas unrelated correct rejections show greater reliance on salient
      categorical cues to support quick and accurate memory decisions. 

PMID- 25862564
TI  - DSM-5 personality traits discriminate between posttraumatic stress disorder and
      control groups.
AB  - The relevance of personality traits to the study of psychopathology has long been
      recognized, particularly in terms of understanding patterns of comorbidity. In
      fact, a multidimensional personality trait model reflecting five higher-order
      personality dimensions-negative affect, detachment, antagonism, disinhibition,
      and psychoticism-is included in the fifth edition of the Diagnostic and
      Statistical Manual of Mental Disorders (DSM-5) and represented in the Personality
      Inventory for DSM-5 (PID-5). However, evaluation of these dimensions and
      underlying personality facets within clinical samples has been limited. In the
      present study, we utilized the PID-5 to evaluate the personality profile
      elevation and composition of 150 control veterans and 35 veterans diagnosed with
      posttraumatic stress disorder (PTSD). Results indicated that veterans with PTSD
      endorsed significantly more personality pathology than control veterans, with
      scores on detachment and psychoticism domains most clearly discriminating between
      the two groups. When personality domain scores were considered as parts of each
      subject's personality profile, a slightly different picture emerged.
      Specifically, the PTSD composition was primarily characterized by detachment and
      negative affect, followed by disinhibition, psychoticism, and antagonism in that
      order of relative importance. The profile of the control group was significantly
      different, mostly accounted for differences in antagonism and psychoticism. Using
      these complementary analytic strategies, the findings demonstrate the relevance
      of personality pathology to PTSD, highlight internalizing features of PTSD, and
      pave the way for future research aimed at evaluating the role of shared
      maladaptive personality traits in underlying the comorbidity of PTSD and related
      disorders. 

PMID- 25862565
TI  - Systematic review of stigma reducing interventions for African/Black diasporic
      women.
AB  - INTRODUCTION: Literature indicates that racism, sexism, homophobia and HIV
      related stigma have adverse impacts on health, well-being, and quality of life
      among HIV-positive women of African descent (African/Black diaspora). However,
      limited evidence exists on the effectiveness of interventions aimed at reducing
      stigma tailored for these women. This study systematically reviewed randomized
      controlled trials (RCTs), non-randomized observational and quasi-experimental
      studies evaluating the effectiveness of interventions aimed at reducing stigma
      experienced by this population. METHODS: The Cochrane methodology was used to
      develop a search strategy in consultation with a librarian scientist. Databases
      searched included the Cochrane Library, Ovid EMBASE, PsycInfo, and 10 others. Two
      reviewers independently assessed the studies for potential relevance and
      conducted the Cochrane grading of RCTs to assess risk of bias and the Newcastle
      Ottawa scale to assess the quality of non-randomized studies. Eligible papers
      were selected if they employed an intervention design with African/Black
      diasporic women living with HIV as the target population and had a primary
      outcome of stigma reduction. RESULTS: Of the five studies that met all of the
      eligibility criteria, four demonstrated the effectiveness of interventions in
      reducing HIV-related stigma. Only two of the five studies were designed
      specifically for HIV-positive African/Black diasporic women. Limitations included
      the absence of interventions addressing other forms of stigma and discrimination
      (e.g. gender discrimination, racism, heterosexism). CONCLUSIONS: Our findings
      suggest that there are limited interventions designed to address multiple forms
      of stigma, including gender and racial discrimination, experienced by HIV
      positive African/Black diasporic women.

PMID- 25862566
TI  - Risk factors for superficial incisional surgical site infection after
      gastrectomy: analysis of patients enrolled in a prospective randomized trial
      comparing skin closure methods.
AB  - BACKGROUND: Surgical site infection is one of the commonest complications of
      gastrointestinal surgery. The nature of surgical procedures and wound closure
      methods may influence the incidence of superficial incisional surgical site
      infection. Patients enrolled in a prospective randomized controlled trial
      comparing skin closure methods are the best subjects for analyzing surgical site
      infection risk. METHOD: From a cohort of 1080 patients who had been enrolled in
      our previous randomized controlled trial, data for 685 patients who had undergone
      elective open total gastrectomy or distal gastrectomy for gastric cancer were
      extracted. The incidences of superficial incisional surgical site infection after
      total gastrectomy and distal gastrectomy were compared and risk factors for
      superficial incisional surgical site infection were investigated by univariate
      analyses using logistic regression models. RESULTS: In all, 42 patients (6.1 %)
      developed superficial incisional surgical site infections after gastrectomy; 15
      of 288 patients (5.2 %) developed these infections after total gastrectomy, and
      27 of 397 patients (6.8 %) developed these infections after distal gastrectomy
      these differences are not significant. According to univariate analysis, age (75
      years or older or younger than 75 years) was the only risk factor for superficial
      incisional surgical site infections (P = 0.049). There was a tendency for the
      incidence of superficial incisional surgical site infection to increase in
      parallel with age. CONCLUSION: The incidence of superficial incisional surgical
      site infection did not differ between total gastrectomy and distal gastrectomy.
      Advanced age was the only identified risk factor for superficial incisional
      surgical site infections after gastrectomy.

PMID- 25862568
TI  - Meristem control of leaf patterning.

PMID- 25862567
TI  - Osteopontin, E-cadherin, and beta-catenin expression as prognostic biomarkers in
      patients with radically resected gastric cancer.
AB  - A correlation between osteopontin, E-cadherin, beta-catenin, and cyclooxygenase 2
      overexpression and poor clinicopathological features and prognosis has been
      previously suggested in gastric cancer. This translational study was aimed at
      assessing the correlation of these immunohistochemical biomarkers with outcome in
      patients with radically resected gastric cancer. We analyzed osteopontin, E
      cadherin, beta-catenin, and cyclooxygenase 2 expression by immunohistochemistry
      in 346 primary gastric tumor tissue samples from patients enrolled in the ITACA-S
      trial. This phase III study randomized patients with radically resected gastric
      cancer to receive adjuvant chemotherapy with either 5-fluorouracil and leucovorin
      or a sequential regimen of infusional 5-fluorouracil and leucovorin plus
      irinotecan followed by cisplatin and docetaxel. High expression of osteopontin
      was correlated with high histological grade, diffuse histotype, and peritoneal
      relapse, but not with TNM stage. Moreover, osteopontin overexpression was
      associated with higher risk of tumor recurrence and metastases, and was an
      independent prognostic factor for both relapse-free and overall survival of
      gastric cancer patients following adjuvant chemotherapy. Abnormal E-cadherin
      expression and abnormal beta-catenin expression were correlated with more
      advanced disease stage, and as a consequence, with poor outcome. Our results
      suggest that osteopontin overexpression is a valuable independent predictor of
      tumor recurrence and survival in patients with radically resected gastric cancer.

PMID- 25862569
TI  - Using mycorrhiza-defective mutant genotypes of non-legume plant species to study
      the formation and functioning of arbuscular mycorrhiza: a review.
AB  - A significant challenge facing the study of arbuscular mycorrhiza is the
      establishment of suitable non-mycorrhizal treatments that can be compared with
      mycorrhizal treatments. A number of options are available, including soil
      disinfection or sterilisation, comparison of constitutively mycorrhizal and non
      mycorrhizal plant species, comparison of plants grown in soils with different
      inoculum potential and the comparison of mycorrhiza-defective mutant genotypes
      with their mycorrhizal wild-type progenitors. Each option has its inherent
      advantages and limitations. Here, the potential to use mycorrhiza-defective
      mutant and wild-type genotype plant pairs as tools to study the functioning of
      mycorrhiza is reviewed. The emphasis of this review is placed on non-legume plant
      species, as mycorrhiza-defective plant genotypes in legumes have recently been
      extensively reviewed. It is concluded that non-legume mycorrhiza-defective mutant
      and wild-type pairs are useful tools in the study of mycorrhiza. However, the
      mutant genotypes should be well characterised and, ideally, meet a number of key
      criteria. The generation of more mycorrhiza-defective mutant genotypes in
      agronomically important plant species would be of benefit, as would be more
      research using these genotype pairs, especially under field conditions. 

PMID- 25862570
TI  - Progesterone attenuates thrombin-induced endothelial barrier disruption in the
      brain endothelial cell line bEnd.3: The role of tight junction proteins and the
      endothelial protein C receptor.
AB  - This study examines the effects of progesterone on blood-brain barrier (BBB)
      integrity following thrombin administration. Thrombin is expressed in many
      diseases which affect neural tissue and is associated with breakdown of the BBB.
      Progesterone has shown protective effects on the BBB in stroke and traumatic
      brain injury. METHODS: Mouse brain endothelial (bEnd.3) cells were treated with
      progesterone (20 MUmol/l) for 24h before thrombin administration (60 U/ml). BBB
      permeability was measured by transendothelial electrical resistance (TEER),
      because TEER decrease is associated with BBB compromise. Tight junction (TJ)
      proteins (occludin, claudin-5, and zonula occludens-1) and endothelial protein C
      receptor (EPCR) were analyzed. RESULTS: Thrombin decreased TEER and progesterone
      prevented that decrease. TJ proteins and EPCR were also decreased after thrombin
      treatment and progesterone treatment blocked that effect. CONCLUSION:
      Progesterone can attenuate thrombin-induced BBB disruption by blocking the
      degradation of TJ proteins and EPCR in bEnd.3 cells.

PMID- 25862571
TI  - The primate seahorse rhythm.
AB  - The main Zeitgeber, the day-night cycle, synchronizes the central oscillator
      which determines behaviors rhythms as sleep-wake behavior, body temperature, the
      regulation of hormone secretion, and the acquisition and processing of memory.
      Thus, actions such as acquisition, consolidation, and retrieval performed in the
      hippocampus are modulated by the circadian system and show a varied dependence on
      light and dark. To investigate changes in the hippocampus' cellular mechanism
      invoked by the day and night in a diurnal primate, this study analyzed the
      expression of PER2 and the calcium binding proteins (CaBPs) calbindin, calretinin
      and parvalbumin in the hippocampus of Sapajus apella, a diurnal primate, at two
      different time points, one during the day and one during the dark phase. The PER2
      protein expression peaked at night in the antiphase described for the
      suprachiasmatic nucleus (SCN) of the same primate, indicating that hippocampal
      cells can present independent rhythmicity. This hippocampal rhythm was similar to
      that presented by diurnal but not nocturnal rodents. The CaBPs immunoreactivity
      also showed day/night variations in the cell number and in the cell morphology.
      Our findings provide evidence for the claim that the circadian regulation in the
      hippocampus may involve rhythms of PER2 and CaBPs expression that may contribute
      to the adaptation of this species in events and activities relevant to the
      respective periods. 

PMID- 25862573
TI  - Cerebral microvascular pericytes and neurogliovascular signaling in health and
      disease.
AB  - Increases in neuronal activity cause an enhanced blood flow to the active brain
      area. This neurovascular coupling is regulated by multiple mechanisms: Adenosine
      and lactate produced as metabolic end-products couple activity with flow by
      inducing vasodilation. As a specific mechanism to the brain, synaptic activity
      induced Ca(2+) increases in astrocytes, interneurons and neurons translate
      neuronal activity to vasoactive signals such as arachidonic acid metabolites and
      NO. K(+) released onto smooth muscle cells through Ca(2+)-activated K(+) channels
      on end-feet can also induce vasodilation during neuronal activity. An intense
      communication between the endothelia, pericytes and astrocytes is required for
      development and functioning of the neurovascular unit as well as the BBB. The
      ratio of pericytes to endothelial cells is higher in the cerebral
      microcirculation than other tissues. Pericytes play a role in distribution of
      microvascular blood flow in response to the local demand as a final regulatory
      step after arterioles, which feed a larger cohort of cells. Pericyte-endothelial
      communication is essential for vasculogenesis. Pericyte also take part in
      leukocyte infiltration and immune responses. The microvascular injury induced by
      ischemia/reperfusion plays a critical role in tissue survival after
      recanalization by inducing sustained pericyte contraction and microcirculatory
      clogging (no-reflow) and by disrupting BBB integrity. Suppression of
      oxidative/nitrative stress or sustained adenosine delivery during re-opening of
      an occluded artery improves the outcome of recanalization by promoting
      microcirculatory reflow. Pericyte dysfunction in retinal microvessels is the main
      cause of diabetic retinopathy. Recent findings suggest that the age-related
      microvascular dysfunction may initiate the neurodegenerative changes seen
      Alzheimer's dementia. This article is part of a Special Issue entitled SI: Cell
      Interactions In Stroke. 

PMID- 25862572
TI  - Effects of discontinuing a high-fat diet on mitochondrial proteins and 6
      hydroxydopamine-induced dopamine depletion in rats.
AB  - Diet-induced obesity can increase the risk for developing age-related
      neurodegenerative diseases including Parkinson's disease (PD). Increasing
      evidence suggests that mitochondrial and proteasomal mechanisms are involved in
      both insulin resistance and PD. The goal of this study was to determine whether
      diet intervention could influence mitochondrial or proteasomal protein expression
      and vulnerability to 6-Hydroxydopamine (6-OHDA)-induced nigrostriatal dopamine
      (DA) depletion in rats' nigrostriatal system. After a 3 month high-fat diet
      regimen, we switched one group of rats to a low-fat diet for 3 months (HF-LF
      group), while the other half continued with the high-fat diet (HF group). A chow
      group was included as a control. Three weeks after unilateral 6-OHDA lesions, HF
      rats had higher fasting insulin levels and higher Homeostasis model assessment of
      insulin resistance (HOMA-IR), indicating insulin resistance. HOMA-IR was
      significantly lower in HF-LF rats than HF rats, indicating that insulin
      resistance was reversed by switching to a low-fat diet. Compared to the Chow
      group, the HF group exhibited significantly greater DA depletion in the
      substantia nigra but not in the striatum. DA depletion did not differ between the
      HF-LF and HF group. Proteins related to mitochondrial function (such as AMPK, PGC
      1alpha), and to proteasomal function (such as TCF11/Nrf1) were influenced by diet
      intervention, or by 6-OHDA lesion. Our findings suggest that switching to a low
      fat diet reverses the effects of a high-fat diet on systemic insulin resistance,
      and mitochondrial and proteasomal function in the striatum. Conversely, they
      suggest that the effects of the high-fat diet on nigrostriatal vulnerability to 6
      OHDA-induced DA depletion persist. 

PMID- 25862574
TI  - K(ATP) channels and MPTP are involved in the cardioprotection bestowed by chronic
      intermittent hypobaric hypoxia in the developing rat.
AB  - The aim of this study was to explore the mechanism underlying the
      cardioprotection bestowed by chronic intermittent hypobaric hypoxia (CIHH)
      against ischemia/reperfusion (I/R) injury in developing rats. Neonatal male rats
      were subjected to CIHH treatments that simulated an altitude of 3000 m a.s.l. for
      28 days (CIHH28) and 42 days (CIHH42), respectively, or no treatment (control).
      The left ventricular function of isolated hearts was evaluated. The ultra
      microstructure, superoxide dismutase (SOD) activity and total anti-oxidation
      capacity (TAC) of the myocardium were determined. The basic left ventricular
      function remained unchanged in CIHH rats, except for an increased coronary flow.
      The recovery of cardiac function from I/R, however, was much better in CIHH rats
      than in control rats. Compared to control rats, CIHH rats had much higher SOD
      levels and TAC, and the ultra-microstructure damage to mitochondria was
      considerably less. The cardiac protection of CIHH was canceled out by
      glibenclamide, an inhibitor of the ATP-sensitive potassium (K(ATP)) channel, 5
      hydroxydecanoate, an inhibitor of mitochondrial K(ATP) (mitoKATP), and
      atractyloside, an opener of the mitochondrial permeability transition pore
      (MPTP). To the contrary, diazoxide, an opener of mitoKATP, and cyclosporin A, a
      blocker of MPTP opening, induced cardioprotection in control rats. These results
      suggest that CIHH protects the heart against I/R injury in developing rats
      through opening of the K(ATP) channel and inhibiting of opening of the MPTP.

PMID- 25862575
TI  - Aminoguanidine mitigates apoptosis, testicular seminiferous tubules damage, and
      oxidative stress in streptozotocin-induced diabetic rats.
AB  - This study aimed to investigate the effect of aminoguanidine (AG) against
      testicular damage streptozotocin (STZ) induced diabetes. Thirty two rats were
      separated into four groups: control, AG, STZ and STZ+AG. In the STZ group, 12.5+/
      1.3% of tubules were seen as containing sloughed spermatogenic cells into the
      lumen, 28.7+/-1.8% of tubules were atrophic, 46.2+/-2.1% of tubules were
      degenerative and 8.5+/-0.9% of tubules contained giant cells. Statistically, the
      affected tubule number was significantly lower in the STZ+AG group than in the
      STZ group. Intensely stained caspase-3 cells showed a statistically significant
      increase in the STZ group, while it decreased in the STZ+AG group. The enzyme
      activities of catalase (CAT), superoxide dismutase (SOD) and glutathione (GSH)
      level decreased and the level of malondialdehyde (MDA) and nitric oxide (NO)
      increased in the STZ group, while AG treated diabetic rats showed an increase of
      CAT, SOD activity and GSH level and a decrease in MDA and NO levels. This study
      shows that the oxidative stress, increased NO level and apoptotic cell death play
      an important role in diabetic rat testicular damage and that AG treatment of
      diabetic rats results in protection of spermatogenic cells against oxidative
      stress and apoptotic cell death. 

PMID- 25862576
TI  - C4-dicarboxylic acid production by overexpressing the reductive TCA pathway.
AB  - As C4-dicarboxylic acids could replace C4-petrochemicals, the reductive
      tricarboxylic acid (TCA) pathway was overexpressed in Pichia pastoris for
      production of the C4-dicarboxylic acids. Three expression cassettes which carried
      the pyruvate carboxylase gene (pc), the cytoplasmic malate dehydrogenase gene
      (mdh1) and the retargeted fumarase gene (Tfum) were integrated into the
      chromosomal DNA of P. pastoris GS115 alone or jointly. Multicopy integrations
      were screened using quantitative PCR for C4-dicarboxylic acid overaccumulation.
      The results showed that the highest titer in 96 h of fumaric, malic and succinic
      acid (0.76, 42.28 and 9.42 g l(-1)) was obtained by co-expression of pc and mdh1
      in P. pastoris. This is the first report about multiple genes engineered in P.
      pastoris for C4-dicarboxylic acid production. The strain Pp-PC-MDH1, moreover,
      has a significant potential to produce malic acid in aerobic conditions.

PMID- 25862577
TI  - Low-temperature anaerobic digestion is associated with differential methanogenic
      protein expression.
AB  - Anaerobic digestion (AD) is an attractive wastewater treatment technology,
      leading to the generation of recoverable biofuel (methane). Most industrial AD
      applications, carry excessive heating costs, however, as AD reactors are commonly
      operated at mesophilic temperatures while handling waste streams discharged at
      ambient or cold temperatures. Consequently, low-temperature AD represents a cost
      effective strategy for wastewater treatment. The comparative investigation of key
      microbial groups underpinning laboratory-scale AD bioreactors operated at 37, 15
      and 7 degrees C was carried out. Community structure was monitored using 16S rRNA
      clone libraries, while abundance of the most prominent methanogens was
      investigated using qPCR. In addition, metaproteomics was employed to access the
      microbial functions carried out in situ. While delta-Proteobacteria were
      prevalent at 37 degrees C, their abundance decreased dramatically at lower
      temperatures with inverse trends observed for Bacteroidetes and Firmicutes.
      Methanobacteriales and Methanosaeta were predominant at all temperatures
      investigated while Methanomicrobiales abundance increased at 15 degrees C
      compared to 37 and 7 degrees C. Changes in operating temperature resulted in the
      differential expression of proteins involved in methanogenesis, which was found
      to occur in all bioreactors, as corroborated by bioreactors' performance. This
      study demonstrated the value of employing a polyphasic approach to address
      microbial community dynamics and highlighted the functional redundancy of AD
      microbiomes.

PMID- 25862578
TI  - Your chance to quiz a potential future UK health secretary.

PMID- 25862580
TI  - Surgical Management of Multifocal and Multicentric Breast Cancers: Can We Achieve
      the Same, with Less?

PMID- 25862579
TI  - Genetic and epigenetic alterations in hepatitis B virus-associated hepatocellular
      carcinoma.
AB  - Hepatitis B virus (HBV) is a major cause of hepatocellular carcinoma (HCC). Its
      chronic infection can lead to chronic liver inflammation and the accumulation of
      genetic alterations to result in the oncogenic transformation of hepatocytes. HBV
      can also sensitize hepatocytes to oncogenic transformation by causing genetic and
      epigenetic changes of the host chromosomes. HBV DNA can insert into host
      chromosomes and recent large-scale whole-genome sequencing studies revealed
      recurrent HBV DNA integrations sites that may play important roles in the
      initiation of hepatocellular carcinogenesis. HBV can also cause epigenetic
      changes by altering the methylation status of cellular DNA, the post
      translational modification of histones, and the expression of microRNAs. These
      changes can also lead to the eventual hepatocellular transformation. These recent
      findings on the genetic and epigenetic alterations of the host chromosomes
      induced by HBV opened a new avenue for the development of novel diagnosis and
      treatments for HBV-induced HCC. 

PMID- 25862581
TI  - Wide Inter-institutional Variation in Performance of a Molecular Classifier for
      Indeterminate Thyroid Nodules.
AB  - BACKGROUND: The Afirma gene expression classifier (GEC) is used to assess
      malignancy risk in indeterminate thyroid nodules (ITNs) classified as Bethesda
      category III/IV. Our objective was to analyze GEC performance at two institutions
      with high thyroid cytopathology volumes but differing prevalence of malignancy.
      METHODS: Retrospective analysis of all ITNs evaluated with the GEC at Memorial
      Sloan Kettering Cancer Center (MSK; n = 94) and Mount Sinai Beth Israel (MSBI; n
      = 71). These institutions have differing prevalences of malignancy in ITNs: 30-38
      % (MSK) and 10-19 % (MSBI). Surgical pathology was correlated with GEC findings
      for each matched nodule. Performance characteristics were estimated using Bayes
      Theorem. RESULTS: Patient and nodule characteristics were similar at MSK and
      MSBI. The GEC-benign call rates were 38.3 % (MSK) and 52.1 % (MSBI). Of the GEC
      benign nodules, 8.3 % (MSK) and 13.5 % (MSBI) were treated surgically. Surgical
      pathology indicated that all of GEC-benign nodules were benign. Of the GEC
      suspicious nodules, 60.0 % (MSK) and 61.7 % (MSBI) underwent surgery. Positive
      predictive values (PPVs) for GEC-suspicious results were 57.1 % (95 % CI 41.0
      72.3) at MSK and 14.3 % (95 % CI 0.2-30.2) at MSBI. The estimated negative
      predictive values (NPVs) were 86-92 % at MSK and 95-98 % at MSBI. CONCLUSIONS:
      There were wide variations in the Afirma GEC-benign call rate, PPV, and NPV
      between MSBI (a comprehensive health system) and MSK (a tertiary referral cancer
      center), which had differing rates of malignancy in ITNs. The GEC could not
      routinely alter management in either institution. We believe that this assay
      would be expected to be most informative in practice settings where the
      prevalence of malignancy is 15-21 %, such that NPV >95 % and PPV >25 % would be
      anticipated. Knowing the prevalence of malignancy in ITNs at a particular
      institution is critical for reliable interpretation of GEC results.

PMID- 25862582
TI  - Salvage Esophagectomy After Definitive Chemoradiotherapy for Patients with
      Esophageal Squamous Cell Carcinoma: Who Really Benefits from this High-Risk
      Surgery?
AB  - PURPOSE: The aim of this study was to identify good candidates for salvage
      esophagectomy after definitive chemoradiotherapy (dCRT), based on safety and
      survival. METHODS: Sixty-three patients who underwent salvage esophagectomy,
      after dCRT, at the Cancer Institute Hospital, Tokyo, Japan, between 1988 and
      2013, were retrospectively analyzed. Short-term outcomes were evaluated by
      reviewing postoperative complications, length of postoperative hospital stay, and
      mortality. Survival rates were calculated using the Kaplan-Meier method, and
      statistical significance was determined using the log-rank test. The Cox
      proportional hazards model was used for univariate and multivariate analyses of
      overall survival. Univariate logistic regression analysis was used to identify
      factors related to R0 resection. RESULTS: Postoperative complications occurred in
      41 patients (65.1 %), and the mortality rate was 7.9 %. In-hospital deaths did
      not occur among patients with less advanced tumors prior to dCRT (cT1-2 and cN0),
      or among those who had previously achieved a complete response (CR); the 3- and 5
      year overall survival rates were 29.8 % and 15.0 %, respectively. Univariate
      analysis revealed that residual disease, tumor depth, dCRT response, lymph node
      metastasis, and time to relapse were significant factors affecting overall
      survival. Multivariate analysis demonstrated that R0 resection and ypT0-2 tumors
      were significant, favorable prognostic factors in patients undergoing salvage
      esophagectomy. In addition, cT1-2 tumors, initially resectable tumors, ycT1-2
      tumors, and relapse after CR were factors predicting R0 resection. CONCLUSIONS:
      Based on both short- and long-term outcomes, patients with pretreatment or
      preoperative T1-2 tumors and those with relapse after CR are good candidates for
      salvage esophagectomy.

PMID- 25862583
TI  - Sarcopenia is a Predictor of Postoperative Respiratory Complications in Patients
      with Esophageal Cancer.
AB  - BACKGROUND: Depletion of skeletal muscle mass (sarcopenia) indicates a poor
      prognosis for patients with several kinds of cancer, but it remains unclear
      whether esophageal squamous cell carcinoma (ESCC) is among these cancers. The aim
      of this study was to clarify the relationship between sarcopenia and
      postoperative outcome in patients with ESCC treated by esophagectomy. METHODS:
      Skeletal muscle mass was assessed in 138 patients who underwent esophagectomy
      from August 2009 to May 2014. A multifrequency bioelectrical impedance analysis
      (InBody 720; Biospace, Tokyo, Japan) was used to assess skeletal muscle mass just
      before surgery. Postoperative complications were graded according to the Clavien
      Dindo classification, and univariate and multivariate analyses were performed for
      postoperative respiratory complications. RESULTS: Sarcopenia was determined in 61
      patients (44.2 %). Preoperative pulmonary function was significantly lower and
      the rate of respiratory complications significantly higher in the sarcopenia
      group than in the non-sarcopenia group (p < 0.01). For other complications, the
      differences were not significant. Multivariate analysis showed that sarcopenia
      [odds ratio (OR) 5.82; p = 0.0001] and longer operation time (OR 3.09; p = 0.04)
      were risk factors for the occurrence of respiratory complications. CONCLUSIONS:
      Sarcopenia may be a predictor of pulmonary complications after esophagectomy.
      Further analysis is needed to clarify whether nutritional intervention improves
      skeletal muscle mass and thus contributes to reducing postoperative respiratory
      complications in sarcopenic patients.

PMID- 25862584
TI  - Erratum to: Lymph Node Metastasis Predicts Disease Recurrence in a Single-Center
      Experience of 70 Stages 1-3 Appendix Cancers: A Retrospective Review.

PMID- 25862585
TI  - Neurofilaments and NFL-TBS.40-63 peptide penetrate oligodendrocytes through
      clathrin-dependent endocytosis to promote their growth and survival in vitro.
AB  - Neurofilaments (NF) are released into the cerebrospinal fluid (CSF) during
      multiple sclerosis (MS), but their role outside the axon is still unknown. In
      vitro NF fractions, as well as tubulin (TUB), increase oligodendrocyte (OL)
      progenitor proliferation and/or their differentiation depending on the stage of
      their purification (Fressinaud et al., 2012). However the mechanism by which NF
      enter these cells, as well as that of synthetic peptides displaying NFL-tubulin
      binding site (NFL-TBS.40-63) (Fressinaud and Eyer, 2014), remains elusive. Using
      rat OL secondary cultures we localized NF, TUB, and NFL-TBS.40-63 by double
      immunocytochemistry and confocal microscopy. After treating OL cultures with NF
      P2 (2nd pellet of the purification), or TRITC-TUB, these proteins were localized
      in the cytoplasmic processes of myelin basic protein (MBP+) expressing OL.
      Similarly biotinylated NFL-TBS.40-63 synthetic peptides and KER-TBS.1-24 were
      detected in OL progenitors, differentiated (CNP+) and MBP+ OL. In addition, NFL
      TBS.40-63 colocalized with cholera toxin, a known marker of endocytosis, within
      the cells. Pretreatment of OL by methyl beta cyclodextrin abolishes both cholera
      toxin and NFL-TBS.40-63 uptake, indicating endocytosis. Clathrin-dependent
      endocytosis was further confirmed by treatment with dynasore, a dynamin
      inhibitor, which inhibited the uptake of peptides, as well as NFP2 fractions, by
      50%. This study demonstrates that axon cytoskeletal proteins and peptides can be
      internalized by OL through endocytosis. This process could be involved during
      demyelination, and the release of axon proteins might promote remyelination. 

PMID- 25862587
TI  - Astrocytes: Orchestrating synaptic plasticity?
AB  - Synaptic plasticity is the capacity of a preexisting connection between two
      neurons to change in strength as a function of neural activity. Because synaptic
      plasticity is the major candidate mechanism for learning and memory, the
      elucidation of its constituting mechanisms is of crucial importance in many
      aspects of normal and pathological brain function. In particular, a prominent
      aspect that remains debated is how the plasticity mechanisms, that encompass a
      broad spectrum of temporal and spatial scales, come to play together in a
      concerted fashion. Here we review and discuss evidence that pinpoints to a
      possible non-neuronal, glial candidate for such orchestration: the regulation of
      synaptic plasticity by astrocytes. 

PMID- 25862586
TI  - Small constrained SP1-7 analogs bind to a unique site and promote anti-allodynic
      effects following systemic injection in mice.
AB  - Previous results have shown that the substance P (SP) N-terminal fragment SP1-7
      may attenuate hyperalgesia and produce anti-allodynia in animals using various
      experimental models for neuropathic pain. The heptapeptide was found to induce
      its effects through binding to and activating specific sites apart from any known
      neurokinin or opioid receptor. Furthermore, we have applied a medicinal chemistry
      program to develop lead compounds mimicking the effect of SP1-7. The present
      study was designed to evaluate the pharmacological effect of these compounds
      using the mouse spared nerve injury (SNI) model of chronic neuropathic pain.
      Also, as no comprehensive screen with the aim to identify the SP1-7 target has
      yet been performed we screened our lead compound H-Phe-Phe-NH2 toward a panel of
      drug targets. The extensive target screen, including 111 targets, did not reveal
      any hit for the binding site among a number of known receptors or enzymes
      involved in pain modulation. Our animal studies confirmed that SP1-7, but also
      synthetic analogs thereof, possesses anti-allodynic effects in the mouse SNI
      model of neuropathic pain. One of the lead compounds, a constrained H-Phe-Phe-NH2
      analog, was shown to exhibit a significant anti-allodynic effect. 

PMID- 25862588
TI  - Brainstem areas activated by intermittent apnea in awake unrestrained rats.
AB  - We investigated the role of the autonomic nervous system to cardiovascular
      responses to obstructive apnea in awake, unrestrained rats, and measured
      expression of Fos induced by apnea in the brainstem. We implanted a tracheal
      balloon contained in a rigid tube to allow the induction of apnea without
      inducing pain in the trachea. During bouts of 15s of apnea, heart rate fell from
      371+/-8 to 161+/-11bpm (mean+/-SEM, n=15, p<0.01) and arterial pressure increased
      from 115+/-2 to 131+/-4mmHg (p<0.01). Bradycardia was due to parasympathetic
      activity because it was blocked by the muscarinic antagonist, methylatropine. The
      pressor response was due to vasoconstriction caused by sympathetic activation
      because it was blocked by the alpha1 antagonist, prazosin. Apnea induced Fos
      expression in several brainstem areas involved in cardiorespiratory control such
      as the nucleus of the solitary tract (NTS), ventrolateral medulla (VLM), and
      pons. Ligation of the carotid body artery reduced apnea-induced bradycardia,
      blocked heart rate responses to i.v. injection of cyanide, reduced Fos expression
      in the caudal NTS, and increased Fos expression in the rostral VLM. In
      conclusion, apnea activates neurons in regions that process signals from
      baroreceptors, chemoreceptors, pulmonary receptors, and regions responsible for
      autonomic and respiratory activity both in the presence and absence of carotid
      chemoreceptors. 

PMID- 25862590
TI  - Peripheral Blood Plasmacytoid Dendritic Cells at Day 100 Can Predict Outcome
      after Allogeneic Stem Cell Transplantation.
AB  - The rapidly increasing use of allogeneic stem cell transplantation (allo-SCT)
      emphasizes the need for identifying variables predictive of its outcome.
      Plasmacytoid dendritic cells (pDCs) play a major role in establishing immune
      competence and in several autoimmune diseases. Thus, we investigated whether pDCs
      might influence the outcome of patients after allo-SCT in 79 consecutive patients
      who underwent this procedure. pDCs were identified in the blood of patients at
      day 100 after allo-SCT by staining peripheral blood mononuclear cells for surface
      markers and intracellular cytokines and analyzing them on a flow cytometer. We
      found the pDC level at day 100 was not influenced by patient or graft
      characteristics, and only the absence of previous grades II to IV acute graft
      versus-host disease was significantly associated with higher levels of blood pDCs
      after allo-SCT (OR, .67; 95% CI, .54 to .83; P = .0004). Using the median value
      of pDCs at day 100 to divide the patients into 2 distinct groups, we observed
      that a low pDC level was correlated with a worse overall survival (55% versus
      86%, P = .007). In a multivariate analysis, only low pDC level (OR, 3.41; 95% CI,
      1.19 to 9.79; P = .02) and older patient age (OR, 5.16; 95% CI, 1.15 to 23.14; P
      = .03) were significantly predictive of increased risk of death. We conclude that
      monitoring of pDC may be useful for patient management and may have a significant
      impact on the probability of a favorable outcome of allo-SCT.

PMID- 25862589
TI  - Design and Validation of an Augmented Hematopoietic Cell Transplantation
      Comorbidity Index Comprising Pretransplant Ferritin, Albumin, and Platelet Count
      for Prediction of Outcomes after Allogeneic Transplantation.
AB  - Pretransplant values of serum ferritin, albumin, and peripheral blood counts were
      previously suggested to provide prognostic information about hematopoietic cell
      transplantation (HCT) outcomes. Whether these "biomarkers" have prognostic value
      independent of each other and the HCT-comorbidity index (HCT-CI) is unknown. We
      analyzed data from 3917 allogeneic HCT recipients at multiple sites in the United
      States and Italy using multivariate models including each biomarker and the HCT
      CI. Data from all sites were then randomly divided into a training set (n = 2352)
      to develop weights for the relevant biomarkers to be added to the HCT-CI scores
      and a validation set (n = 1407) to validate an augmented HCT-CI compared with the
      original index. Multivariate analysis with data from one site showed that
      ferritin, albumin, and platelets-not neutrophils or hemoglobin-were independently
      associated with increased nonrelapse mortality (NRM) and decreased overall
      survival. Findings were validated in data from the other sites. Subsequently, in
      a training set from all sites, ferritin >2500 mg/dL (hazard ratio [HR], 1.69);
      albumin 3 to 3.5 g/dL (HR, 1.61) and <3.0 g/dL (HR, 2.27); and platelets 50 to
      <100,000 (HR, 1.28), 20 to <50,000 (HR, 1.29), and <20,000 (HR, 1.55) were
      statistically significantly associated with NRM. Weights were assigned to these
      laboratory values following the same equation used to design the original index.
      In the validation set, the addition of the biomarkers to the original index to
      develop an augmented HCT-CI resulted in a statistically significant increase in a
      higher c-statistic estimate for prediction of NRM (P = .0007). Ferritin, albumin,
      and platelet counts are important prognostic markers that further refine the
      discriminative power of the HCT-CI for transplant outcomes.

PMID- 25862592
TI  - [B-mode sonography visualizing microemboli flow in the main cerebral arteries].
AB  - In a patient with a mechanical prosthetic aortic valve admitted for transient
      amnesia, transcranial duplex Doppler and B-mode sonography visualized the transit
      of microemboli along the main cerebral arteries. Gaseous microemboli resulting
      from a cavitation phenomenon at valve closure were seen as high-intensity
      transient signals (HITS). To our knowledge, this is the first report of
      microemboli flow visualized in B-mode. 

PMID- 25862591
TI  - Prospective Validation of the Predictive Power of the Hematopoietic Cell
      Transplantation Comorbidity Index: A Center for International Blood and Marrow
      Transplant Research Study.
AB  - Prospective validation of the hematopoietic cell transplantation-comorbidity
      index (HCT-CI) using contemporary patients treated with hematopoietic cell
      transplantation (HCT) across the Unites States is necessary to confirm its
      widespread applicability. We performed a prospective observational study
      including all patients (8115 recipients of allogeneic and 11,652 recipients of
      autologous HCT) who underwent a first HCT that was reported to the Center for
      International Blood and Marrow Transplant Research between 2007 and 2009. In
      proportional hazards models, increased HCT-CI scores were independently
      associated with increases in hazard ratios for nonrelapse mortality (NRM) (P <
      .0001) and overall mortality (P < .0001) among recipients of allogeneic HCT. HCT
      CI scores of >=3 were uniformly associated with higher risks for outcomes in both
      allogeneic and autologous HCT and in all subgroups, regardless of diagnoses, age,
      and conditioning intensity. Recipients of allogeneic HCT with scores of 1 and 2
      who were ages < 18 years or were treated with lower intensity conditioning
      regimens had similar outcomes compared with those with a score of 0. Higher risks
      for overall mortality, but not for NRM, were observed among recipients of
      autologous HCT with scores of 1 and 2 versus 0. Our results confirm the validity
      the HCT-CI in both allogeneic and autologous HCT. The index should be used as a
      valid standard-of-care health measure in counseling patients for HCT, in clinical
      trial design, and in adjusting outcome analyses. 

PMID- 25862593
TI  - [Post-trauma cerebral thrombophlebitis revealed by psychiatric disorders].
AB  - Head injuries are described in the literature as a rare but possible etiology of
      cerebral venous thrombosis although no pathophysiological link has been
      identified. Trauma-related venous thrombi occurring in the brain produce a broad
      spectrum of clinical presentations. A purely psychiatric term is exceptional,
      leading to misinterpretation and late diagnosis. Positive diagnosis has been
      greatly improved by advances in magnetic resonance imaging with venous phase
      angiography, currently the gold standard exploration. We report the case of a
      patient who presented with post-trauma cerebral venous thrombosis revealed by
      psychiatric disorders. 

PMID- 25862594
TI  - [Femoral arteriovenous fistula due to a knife wound during a fantasia
      performance].

PMID- 25862595
TI  - Nodo- and fasciculoventricular pathways: Electrophysiological features and a
      proposed diagnostic algorithm for preexcitation variants.

PMID- 25862596
TI  - Early menarche is associated with increased risk of asthma: Prospective
      population-based study of twins.
AB  - AIM: To examine the association between early menarche and risk of post
      menarcheal asthma. METHODS: Using data from two multidisciplinary questionnaire
      surveys, conducted eight years apart, we prospectively studied 10,648 female
      twins, 12-41 years of age, from the nationwide Danish Twin Registry. Early
      menarche was defined as menarche before 12 years of age. We performed a cohort
      analysis and a co-twin control analysis including twin pairs discordant for
      incident asthma. RESULTS: Early menarche was observed in 9.3% of the individuals.
      The eight-year cumulative incidence of asthma was higher in girls with early
      menarche compared to girls without early menarche (7.4 vs. 4.5%), OR = 1.71 (1.31
      2.22), p < 0.001; also after adjustment for BMI, current age, physical activity,
      education, and smoking, OR = 1.53 (1.15-2.04), p = 0.003. The unadjusted risk of
      asthma was increased by 8% (1-15%), p = 0.041 per year earlier menarche occurred.
      Among 167 twin pairs discordant for incident asthma, there was a non-significant
      tendency towards early menarche being more common in the asthmatic than the non
      asthmatic co-twin (12.0 vs. 9.6%), OR = 1.57 (0.61-4.05), p = 0.350. The risk of
      asthma was not uniform in discordant monozygotic and dizygotic twins. CONCLUSION:
      Early menarche is associated with increased risk of asthma among Danish female
      twins independently of BMI, age, physical activity, educational level and
      smoking. Results indicate a complex relationship possibly mediated through innate
      and non-genetic effects.

PMID- 25862597
TI  - Cost effectiveness of treating multi-drug resistant tuberculosis by adding
      DeltybaTM to background regimens in Germany.
AB  - OBJECTIVE: To assess the cost-effectiveness of adding delamanid (DeltybaTM) to a
      background regimen (BR) for treating multidrug-resistant tuberculosis (MDR-TB) in
      Germany. METHODS: The incremental cost-effectiveness of treating a cohort of MDR
      TB patients, 38-years old on average, with DeltybaTM plus BR versus a five drug-
      BR regimen alone was compared in a Markov model over a period of 10 years. Cost
      per quality-adjusted life year (QALY) and disability-adjusted life years (DALY)
      were determined from a societal perspective. Recent data from a German cost
      calculation on MDR-TB were applied to the 24-month outcome results of patients
      participating in the placebo-controlled, phase II Otsuka's Trial 204. Costs and
      effectiveness were discounted at a rate of 3% and subjected to deterministic as
      well as probabilistic sensitivity analysis in a Monte Carlo simulation. RESULTS:
      Based on the current market prices the total discounted cost per patient on BR
      plus DeltybaTM was ?142,732 compared to ?150,909 for BR alone. The total
      discounted QALYs per patient were 8.47 for DeltybaTM versus 6.13 for BR alone.
      Accordingly, the addition of DeltybaTM proved to be dominant over the BR alone
      strategy by simultaneously saving ?8177 and gaining 2.34 QALYs. DeltybaTM was
      cost saving in 73% of probabilistic sensitivity analyses compared to BR alone and
      100% cost effective at a willingness-to-pay (WTP) threshold of ?10,000.
      CONCLUSIONS: Under conditions prevalent in Germany, DeltybaTM added to a five
      drug BR regimen is likely to be cost-saving compared to BR alone under a wide
      range of assumptions. Adding delamanid remained cost-effective when costs due to
      loss of productivity were excluded as the QALYs gained by lower lethality and a
      higher proportion of successfully treated patients outweighed the delamanid drug
      costs. These results strongly support the application of DeltybaTM in treating
      MDR-TB patients.

PMID- 25862598
TI  - Lung hyaluronan levels are decreased in alpha-1 antiprotease deficiency COPD.
AB  - INTRODUCTION: Hyaluronan (HA), a long-chain polysaccharide, is currently being
      evaluated as a potential therapeutic agent for pulmonary emphysema, based on
      previous studies from this laboratory indicating its protective effect against
      elastic fiber breakdown. To determine whether exogenously administered HA might
      replace a loss of this extracellular matrix component in this disease, we
      measured the content of HA in lung biopsies from both healthy individuals and
      alpha-1 antiprotease-deficient (AAPD) COPD patients with pulmonary emphysema.
      METHODS: Tissue samples (9 from COPD patients, 5 from controls) were digested
      with papain to isolate glycosaminoglycans, and lung HA was quantified with an
      enzyme-linked immunoabsorbent assay. RESULTS: HA was significantly decreased in
      the AAPDCOPD population compared to normal individuals (13.5 vs 21.7 ng/mg wet
      lung; p < 0.01). Furthermore, there was a positive correlation between HA levels
      and the following parameters: 1) percent predicted FEV1 (r = 0.78; p < 0.001), 2)
      percent predicted DLCO (r = 0.74; p < 0.05), and 3) serum levels of AAP (r =
      0.61; p < 0.05). CONCLUSIONS: These findings support the hypothesis that
      depletion of lung HA plays a role in the pathogenesis of pulmonary emphysema, and
      that replacement of this matrix component could slow the progression of the
      disease.

PMID- 25862599
TI  - Transcranial Magnetic Stimulation Changes Response Selectivity of Neurons in the
      Visual Cortex.
AB  - BACKGROUND: Transcranial magnetic stimulation (TMS) is used to selectively alter
      neuronal activity of specific regions in the cerebral cortex. TMS is reported to
      induce either transient disruption or enhancement of different neural functions.
      However, its effects on tuning properties of sensory neurons have not been
      studied quantitatively. OBJECTIVE/HYPOTHESIS: Here, we use specific TMS
      application parameters to determine how they may alter tuning characteristics
      (orientation, spatial frequency, and contrast sensitivity) of single neurons in
      the cat's visual cortex. METHODS: Single unit spikes were recorded with tungsten
      microelectrodes from the visual cortex of anesthetized and paralyzed cats (12
      males). Repetitive TMS (4 Hz, 4 s) was delivered with a 70 mm figure-8 coil. We
      quantified basic tuning parameters of individual neurons for each pre- and post
      TMS condition. The statistical significance of changes for each tuning parameter
      between the two conditions was evaluated with a Wilcoxon signed-rank test.
      RESULTS: We generally find long-lasting suppression which persists well beyond
      the stimulation period. Pre- and post-TMS orientation tuning curves show constant
      peak values. However, strong suppression at non-preferred orientations tends to
      narrow the widths of tuning curves. Spatial frequency tuning exhibits an
      asymmetric change in overall shape, which results in an emphasis on higher
      frequencies. Contrast tuning curves show nonlinear changes consistent with a gain
      control mechanism. CONCLUSIONS: These findings suggest that TMS causes extended
      interruption of the balance between sub-cortical and intra-cortical inputs.

PMID- 25862600
TI  - Slow-oscillatory Transcranial Direct Current Stimulation Modulates Memory in
      Temporal Lobe Epilepsy by Altering Sleep Spindle Generators: A Possible
      Rehabilitation Tool.
AB  - BACKGROUND: Temporal lobe epilepsy (TLE) is often associated with memory
      deficits. Given the putative role for sleep spindles memory consolidation,
      spindle generators skewed toward the affected lobe in TLE subjects may be a
      neurophysiological marker of defective memory. Slow-oscillatory transcranial
      direct current stimulation (sotDCS) during slow waves sleep (SWS) has previously
      been shown to enhance sleep-dependent memory consolidation by increasing slow
      wave sleep and modulating sleep spindles. OBJECTIVE/HYPOTHESIS: To test if anodal
      sotDCS over the affected TL prior to a nap affects sleep spindles and whether
      this improves memory consolidation. METHODS: Randomized controlled cross-over
      study. 12 people with TLE underwent sotDCS (0.75 Hz; 0-250 MUV, 30 min) or sham
      before daytime nap. Declarative verbal and visuospatial learning were tested.
      Fast and slow spindle signals were recorded by 256-channel EEG during sleep. In
      both study arms, electrical source imaging (ESI) localized cortical generators.
      Neuropsychological data were analyzed with general linear model statistics or the
      Kruskal-Wallis test (P or Z < 0.05), and neurophysiological data tested with the
      Mann-Whitney t test and binomial distribution test (P or Z < 0.05). RESULTS: An
      improvement in declarative (P = 0.05) and visuospatial memory performance (P =
      0.048) emerged after sotDCS. SotDCS increased slow spindle generators current
      density (Z = 0.001), with a shift to the anterior cortical areas. CONCLUSIONS:
      Anodal sotDCS over the affected temporal lobe improves declarative and
      visuospatial memory performance by modulating slow sleep spindles cortical source
      generators. SotDCS appears a promising tool for memory rehabilitation in people
      with TLE.

PMID- 25862601
TI  - The Pursuit of DLPFC: Non-neuronavigated Methods to Target the Left Dorsolateral
      Pre-frontal Cortex With Symmetric Bicephalic Transcranial Direct Current
      Stimulation (tDCS).
AB  - BACKGROUND: The dose of transcranial direct current stimulation (tDCS) is defined
      by electrode montage and current, while the resulting brain current flow is more
      complex and varies across individuals. The left dorsolateral pre-frontal cortex
      (lDLPFC) is a common target in neuropsychology and neuropsychiatry applications,
      with varied approaches used to experimentally position electrodes on subjects.
      OBJECTIVE: To predict brain current flow intensity and distribution using
      conventional symmetrical bicephalic frontal 1 * 1 electrode montages to nominally
      target lDLPFC in forward modeling studies. METHODS: Six high-resolution Finite
      Element Method (FEM) models were created from five subjects of varied head size
      and an MNI standard. Seven electrode positioning methods, nominally targeting
      lDLPFC, were investigated on each head model: the EEG 10-10 including F3-F4, F5
      F6, F7-8, F9-F10, the Beam F3-System, the 5-5 cm-Rule and the developed OLE
      System were evaluated as electrode positioning methods for 5 * 5 cm(2)
      rectangular sponge-pad electrodes. RESULTS: Each positioning approach resulted in
      distinct electrode positions on the scalp and variations in brain current flow.
      Variability was significant, but trends across montages and between subjects were
      identified. Factors enhancing electric field intensity and relative targeting in
      lDLPFC include increased inter-electrode distance and proximity to thinner skull
      structures. CONCLUSION: Brain current flow can be shaped, but not focused, across
      frontal cortex by tDCS montages, including intensity at lDLPFC. The OLE-system
      balances lDLPFC targeting and reduced electric field variability, along with
      clinical ease-of-use.

PMID- 25862602
TI  - Metabolic syndrome-associated hepatocellular carcinoma: Questions still
      unanswered.

PMID- 25862603
TI  - Bioprosthetic valve thrombosis: The eyes will not see what the mind does not
      know.

PMID- 25862604
TI  - Hyperfunctional Voice Disorder in Children With Attention Deficit Hyperactivity
      Disorder (ADHD). A Phenotypic Characteristic?
AB  - OBJECTIVE: The purpose of this study was to detect specific vocal aerodynamic
      patterns in attention deficit hyperactivity disorder (ADHD) patients and to
      define a possible new phenotypic feature of this disorder that must be diagnosed
      and treated. STUDY DESIGN: This is a prospective study. METHODS: Seventy-nine
      children aged 5-13 years were recruited: 44 children with ADHD diagnosis and 35
      children, as a control group, matched according to age and gender. All children
      were evaluated in the voice laboratory. Each subject repeated sustained vowels,
      syllables, words, and sentences several times. Intraoral pressure, transglottal
      airflow, microphone, and electroglottograph results were recorded and analyzed.
      Children affected by ADHD, with adequate tolerance, were evaluated endoscopically
      and by the speech therapist. RESULTS: The aerodynamic analysis shows that the
      subglottal pressure is higher and transglottal airflow is lower in ADHD children
      compared with the children of the control group. Those differences are
      statistically significant. The endoscopic physical examination showed vocal
      nodules in 25 children (78.125%) and hyperfunctional vocal behavior in all ADHD
      children studied. CONCLUSIONS: We proposed that every child with ADHD disorder
      must be evaluated from a laryngeal point of view (otolaryngologist and speech
      therapist) as an important part of the diagnosis and global treatment. It could
      be considered as a new phenotypic characteristic of this disorder.

PMID- 25862605
TI  - NIEluter: Predicting peptides eluted from HLA class I molecules.
AB  - The immune system has evolved to make a diverse repertoire of peptides processed
      from self and foreign proteomes, which are displayed in antigen-binding grooves
      of major histocompatibility complex (MHC) proteins at cell surface for
      surveillance by T cells. These antigenic peptides are termed Naturally Processed
      Peptides or Naturally Presented Peptides (NPPs), which play a major role in cell
      mediated immunity and rational vaccine design. Therefore, it is intensely
      desirable to predict NPPs from a given protein antigen, or to foretell if an MHC
      binding peptide can be eluted from a given MHC protein. In this paper, we
      describe NIEluter, an ensemble predictor based on support vector machine (SVM).
      It consists of a combination of five SVM models trained with position-specific
      amino acid composition, position-specific dipeptide composition, Hidden Markov
      Model, binary encoding, and BLOSUM62 feature. NIEluter can predict NPPs of length
      8-11 from six HLA alleles (A0201, B0702, B3501, B4403, B5301, and B5701) at
      present. Evaluated with five-fold cross-validation and independent datasets if
      available, NIEluter shows good performance. It outperforms MHC-NP in 7 out of 24
      types of situation and precedes NetMHC3.2 in most cases, indicating that it is a
      helpful complement to available tools. NIEluter has been implemented as a free
      web service, which can be accessed at http://immunet.cn/nie/cgi-bin/nieluter.pl. 

PMID- 25862606
TI  - Simultaneous assessment of NF-kappaB/p65 phosphorylation and nuclear localization
      using imaging flow cytometry.
AB  - Aberrant activity of Nuclear Factor-kappaB (NF-kappaB) is associated with many
      diseases and is therapeutically targeted. Post-translational modifications,
      particularly phosphorylation of the RELA/p65 sub-unit, are essential for
      cytoplasmic to nuclear localization of NF-kappaB/p65 and initiation of
      transcription of downstream target genes. Immunoblot and phospho-flow cytometry
      have been used to study the relationship between phosphorylation motifs and NF
      kappaB activation and microscopic analysis of nuclear localization of p65 is also
      used as a parameter for activation. The labor intensive nature of these
      approaches commonly limits the number of sampling points or replicates. Recent
      insights into the relationship between p65 phosphorylation motifs and their
      nuclear localization indicate that these parameters have different significances
      and should not be used interchangeably. In this study, we demonstrate feasibility
      and reproducibility of studying the relationship between p65 phosphorylation and
      nuclear translocation using imaging flow cytometry (IFC). TNFalpha- or
      PMA/Ionomycin-induced phosphorylation of p65 at serine 529 in cell line models
      and healthy donor lymphocytes served as the experimental model. IFC analysis
      demonstrated that expression of phosphorylated serine 529 (P-p65(s529)) increased
      rapidly following stimulation and that nuclear localization of P-p65(s529)
      followed the nuclear localization pattern of total p65. However, in the presence
      of tacrolimus, P-p65(s529) expression was inhibited without affecting nuclear
      localization of total p65. The data demonstrate the application of IFC to
      simultaneously assess phosphorylation of p65 and its cellular localization and
      the results obtained by this analysis corroborate current insights regarding the
      specific effect of tacrolimus on serine 529 phosphorylation. 

PMID- 25862607
TI  - Development and validation of a broad scheme for prediction of HLA class II
      restricted T cell epitopes.
AB  - Computational prediction of HLA class II restricted T cell epitopes has great
      significance in many immunological studies including vaccine discovery. In recent
      years, prediction of HLA class II binding has improved significantly but a
      strategy to globally predict the most dominant epitopes has not been rigorously
      defined. Using human immunogenicity data associated with sets of 15-mer peptides
      overlapping by 10 residues spanning over 30 different allergens and bacterial
      antigens, and HLA class II binding prediction tools from the Immune Epitope
      Database and Analysis Resource (IEDB), we optimized a strategy to predict the top
      epitopes recognized by human populations. The most effective strategy was to
      select peptides based on predicted median binding percentiles for a set of seven
      DRB1 and DRB3/4/5 alleles. These results were validated with predictions on a
      blind set of 15 new allergens and bacterial antigens. We found that the top 21%
      predicted peptides (based on the predicted binding to seven DRB1 and DRB3/4/5
      alleles) were required to capture 50% of the immune response. This corresponded
      to an IEDB consensus percentile rank of 20.0, which could be used as a universal
      prediction threshold. Utilizing actual binding data (as opposed to predicted
      binding data) did not appreciably change the efficacy of global predictions,
      suggesting that the imperfect predictive capacity is not due to poor algorithm
      performance, but intrinsic limitations of HLA class II epitope prediction schema
      based on HLA binding in genetically diverse human populations. 

PMID- 25862609
TI  - What are the primary concerns of nursing students as they prepare for and
      contemplate their first clinical placement experience?
AB  - Nursing students' first clinical placement experience can be a critical turning
      point -reinforcing professional aspirations for some, and for others, a time of
      emotional turbulence. There is a paucity of research focusing on students'
      perceptions and concerns prior to their first placement experience. Thus, the aim
      of this study was to explore the concerns of first year bachelor of nursing
      students from one Australian university as they prepared for their first clinical
      placement. Participants completed an online 'readiness for practice' survey
      consisting of 22 items. This paper focuses on participants' responses to the one
      open ended question: 'Please comment on any concerns that you have in relation to
      being prepared for your first clinical placement'. Summative qualitative content
      analysis was used for analysis. 144 students (55%) responded to the open ended
      question. Responses were categorised into six themes including: Not prepared for
      placement; feeling nervous, anxious and worried; bullying and belonging;
      practicalities; patient safety and making mistakes; and working outside of my
      scope of practice. It appears that activities designed to equip students with the
      capacity to manage the inherent challenges of undertaking a clinical placement
      may sometimes have a paradoxical effect by increasing students' level of stress
      and anxiety. An enhanced understanding of students' concerns may help educators
      implement appropriate support strategies. 

PMID- 25862608
TI  - A novel mutation in PNLIP causes pancreatic triglyceride lipase deficiency
      through protein misfolding.
AB  - Congenital pancreatic triglyceride lipase (PNLIP) deficiency is a rare disorder
      with uncertain genetic background as most cases were described before gene
      sequencing was readily available. Recently, two brothers with PNLIP deficiency
      were found to carry a homozygous missense mutation, c.662C>T (p.T221M) in the
      PNLIP gene (J. Lipid Res. 2014. 55:307-312). Molecular modeling suggested the
      substitution would change the orientation of residues in the catalytic site and
      disrupt the function of p.T221M PNLIP. To test the effect of the p.T221M mutation
      on PNLIP function, we expressed wild-type and p.T221M PNLIP in human embryonic
      kidney (HEK) 293A cells and dexamethasone-differentiated AR42J rat acinar cells.
      In both cellular models, wild-type PNLIP was secreted into the conditioned medium
      where it was readily detectable by protein staining, immunoblot or lipase
      activity assays. In contrast, mutant p.T221M was not secreted into the medium,
      but it was present in cell lysates where it accumulated in the insoluble
      fraction. Intracellular retention of mutant p.T221M resulted in endoplasmic
      reticulum (ER) stress as measured by elevated XBP1 splicing and increased levels
      of ER chaperones. Our results demonstrate that the presence of methionine at
      position 221 in the PNLIP protein sequence causes misfolding and aggregation of
      the p.T221M mutant inside the cell. The consequent loss of enzyme secretion
      adequately explains the clinical phenotype of PNLIP deficiency reported for
      homozygous carriers of p.T221M. Furthermore, the ability of mutant p.T221M to
      induce ER stress suggests that this form of PNLIP deficiency might cause acinar
      cell damage as well. 

PMID- 25862611
TI  - Activation of KV7 channels stimulates vasodilatation of human placental chorionic
      plate arteries.
AB  - INTRODUCTION: Potassium (K(+)) channels are key regulators of vascular smooth
      muscle cell (VSMC) excitability. In systemic small arteries, Kv7 channel
      expression/activity has been noted and a role in vascular tone regulation
      demonstrated. We aimed to demonstrate functional Kv7 channels in human
      fetoplacental small arteries. METHODS: Human placental chorionic plate arteries
      (CPAs) were obtained at term. CPA responses to Kv7 channel modulators was
      determined by wire myography. Presence of Kv7 channel mRNA (encoded by KCNQ1-5)
      and protein expression were assessed by RT-PCR and
      immunohistochemistry/immunofluorescence, respectively. RESULTS: Kv7 channel
      blockade with linopirdine increased CPA basal tone and AVP-induced contraction.
      Pre-contracted CPAs (AVP; 80 mM K(+) depolarization solution) exhibited
      significant relaxation to flupirtine, retigabine, the acrylamide (S)-1, and (S)
      BMS-204352, differential activators of Kv7.1 - Kv7.5 channels. All CPAs assessed
      expressed KCNQ1 and KCNQ3-5 mRNA; KCNQ2 was expressed only in a subset of CPAs.
      Kv7 protein expression was confirmed in intact CPAs and isolated VSMCs.
      DISCUSSION: Kv7 channels are present and active in fetoplacental vessels,
      contributing to vascular tone regulation in normal pregnancy. Targeting these
      channels may represent a therapeutic intervention in pregnancies complicated by
      increased vascular resistance.

PMID- 25862612
TI  - Histopathological and immunohistochemical features of atypical epithelial tumours
      of the gland of the third eyelid in seven dogs.
AB  - This report documents the histopathological and immunohistochemical features of
      atypical epithelial tumours of the gland of the third eyelid (GTE) in seven dogs.
      Cases 1 and 2 were diagnosed as myoepithelioma, comprising of compressive
      proliferations of interlacing bundles of neoplastic spindle cells expressing
      cytokeratin 14, p63, calponin and alpha-smooth muscle actin. Cases 3, 4 and 5
      were diagnosed as complex carcinomas comprising of atypical glandular cells
      expressing cytokeratin 8/18, together with spindle-shaped or round neoplastic
      cells expressing cytokeratin 14, p63, calponin and alpha-smooth muscle actin.
      Cases 6 and 7 were diagnosed as basal cell adenocarcinomas (BCACs) comprising of
      a mixed proliferation of glandular and basal-type cells expressing cytokeratin 14
      and p63. Therefore, in addition to glandular components, these tumours may
      include neoplastic cells with a myoepithelial or basal cell phenotype. Hence,
      there is diversity in the features of epithelial neoplasia of the GTE in dogs,
      similar to tumours in human salivary and lacrimal glands. 

PMID- 25862613
TI  - Quantification of steroidal alkaloids in Buxus papillosa using electrospray
      ionization liquid chromatography-triple quadrupole mass spectrometry.
AB  - Buxus papillosa is one of the most extensively studied species of the genus Buxus
      known to possess steroidal alkaloids which can be used for assessing the various
      pharmacological activities of this plant. This paper describes the liquid
      chromatography-electrospray ionization triple quadrupole mass spectrometry (LC
      ESI-QQQ-MS) method for the quantification of six steroidal alkaloids as chemical
      markers in the extracts of leaves, roots and stems of B. papillosa. Quantitative
      MS/MS analysis was carried out by optimization of the most sensitive transition
      for each analyte. This has yielded detection and quantification limits of 0.486
      8.08 ng/mL and 1.473-24.268 ng/mL, respectively for all analytes. Linearity of
      response was also achieved and the regression coefficient found to be >0.99 for
      all analyzed compounds. The newly developed MRM (Multiple Reaction Monitoring)
      method showed excellent sensitivity for the quantification of steroidal alkaloids
      within 15 min run time. This paper describes the application of LC-QQQ-MS
      technique for steroidal alkaloids analysis in plant samples.

PMID- 25862610
TI  - Practices in prescribing protein substitutes for PKU in Europe: No uniformity of
      approach.
AB  - BACKGROUND: There appears little consensus concerning protein requirements in
      phenylketonuria (PKU). METHODS: A questionnaire completed by 63 European and
      Turkish IMD centres from 18 countries collected data on prescribed total protein
      intake (natural/intact protein and phenylalanine-free protein substitute [PS]) by
      age, administration frequency and method, monitoring, and type of protein
      substitute. Data were analysed by European region using descriptive statistics.
      RESULTS: The amount of total protein (from PS and natural/intact protein) varied
      according to the European region. Higher median amounts of total protein were
      prescribed in infants and children in Northern Europe (n=24 centres) (infants <1
      year, >2-3g/kg/day; 1-3 years of age, >2-3 g/kg/day; 4-10 years of age, >1.5-2.5
      g/kg/day) and Southern Europe (n=10 centres) (infants <1 year, 2.5 g/kg/day, 1-3
      years of age, 2 g/kg/day; 4-10 years of age, 1.5-2 g/kg/day), than by Eastern
      Europe (n=4 centres) (infants <1 year, 2.5 g/kg/day, 1-3 years of age, >2-2.5
      g/kg/day; 4-10 years of age, >1.5-2 g/kg/day) and with Western Europe (n=25
      centres) giving the least (infants <1 year, >2-2.5 g/kg/day, 1-3 years of age,
      1.5-2 g/kg/day; 4-10 years of age, 1-1.5 g/kg/day). Total protein prescription
      was similar in patients aged >10 years (1-1.5 g/kg/day) and maternal patients (1
      1.5 g/kg/day). CONCLUSIONS: The amounts of total protein prescribed varied
      between European countries and appeared to be influenced by geographical region.
      In PKU, all gave higher than the recommended 2007 WHO/FAO/UNU safe levels of
      protein intake for the general population.

PMID- 25862614
TI  - Increased meal frequency attenuates fat-free mass losses and some markers of
      health status with a portion-controlled weight loss diet.
AB  - Increased meal frequency (MF) may be associated with improvements in blood
      markers of health and body composition during weight loss; however, this claim
      has not been validated. The purpose of the study was to determine if either a 2
      meal (2 MF) or 6-meal frequency (6 MF) regimen can improve body composition and
      blood-based markers of health while consuming a portion-controlled
      equihypocaloric diet. Eleven (N=11) obese women (52 +/- 7 years, 101.7 +/- 22.6
      kg, 39.1 +/- 7.6 kg/m(2)) were randomized into treatment condition (2 MF or 6 MF)
      for 2 weeks, completed a 2-week washout, and alternated treatment conditions. In
      pre/post fashion, changes in body composition, glucose, insulin, and lipid
      components were measured in response to a test meal. Body mass was successfully
      lost (P <= .05) under both feeding regimens (2 MF: -2.8 +/- 1.5 vs 6 MF: -1.9 +/-
      1.5 kg). Altering MF did not impact glucose, insulin, total cholesterol, or low
      density lipoprotein cholesterol (P>.05). On average, fat-free mass (FFM)
      decreased by -3.3% +/- 2.6% following the 2 MF condition and, on average,
      increased by 1.2% +/- 1.7% following the 6 MF condition (P <= .05). Fasting high
      density lipoprotein cholesterol (HDL-C) percentage increased during the 2 MF
      condition; this was significantly greater than that in the 6 MF condition (1.3%
      +/- 12.2% vs 0.12% +/- 10.3%) (P <= .05). Overall, reductions in MF (2 MF) were
      associated with improved HDL-C levels; but the clinical significance is not
      clear. Alternatively, increased MF (6 MF) did appear to favorably preserve FFM
      during weight loss. In conclusion, caloric restriction was effective in reducing
      body mass and attenuating FFM changes in body composition; however, glucose,
      insulin, and lipid metabolism had no significant differences between MF.

PMID- 25862615
TI  - Is rituximab effective for IgG4-related disease in the long term? Experience of
      cases treated with rituximab for 4 years.

PMID- 25862616
TI  - Belimumab and the measurement of fatigue.

PMID- 25862618
TI  - Tinnitus: from basic principles to therapy.

PMID- 25862617
TI  - Genome-wide search followed by replication reveals genetic interaction of CD80
      and ALOX5AP associated with systemic lupus erythematosus in Asian populations.
AB  - OBJECTIVES: Genetic interaction has been considered as a hallmark of the genetic
      architecture of systemic lupus erythematosus (SLE). Based on two independent
      genome-wide association studies (GWAS) on Chinese populations, we performed a
      genome-wide search for genetic interactions contributing to SLE susceptibility.
      METHODS: The study involved a total of 1 659 cases and 3 398 controls in the
      discovery stage and 2 612 cases and 3 441 controls in three cohorts for
      replication. Logistic regression and multifactor dimensionality reduction were
      used to search for genetic interaction. RESULTS: Interaction of CD80 (rs2222631)
      and ALOX5AP (rs12876893) was found to be significantly associated with SLE
      (OR_int=1.16, P_int_all=7.7E-04 at false discovery rate<0.05). Single nuclear
      polymorphism rs2222631 was found associated with SLE with genome-wide
      significance (P_all=4.5E-08, OR=0.86) and is independent of rs6804441 in CD80,
      whose association was reported previously. Significant correlation was observed
      between expression of these two genes in healthy controls and SLE cases, together
      with differential expression of these genes between cases and controls, observed
      from individuals from the Hong Kong cohort. Genetic interactions between BLK
      (rs13277113) and DDX6 (rs4639966), and between TNFSF4 (rs844648) and PXK
      (rs6445975) were also observed in both GWAS data sets. CONCLUSIONS: Our study
      represents the first genome-wide evaluation of epistasis interactions on SLE and
      the findings suggest interactions and independent variants may help partially
      explain missing heritability for complex diseases.

PMID- 25862620
TI  - [Somatosensoric tinnitus].
AB  - Tinnitus can be caused or triggered by functional disorders of the cervical
      spine, temporomandibular joint or any other musculoskeletal structure of the neck
      or head. This special form of tinnitus is called somatosensory tinnitus and
      represents a discrete subgroup among the different kinds of tinnitus. Distinctive
      for this kind of tinnitus are alterations in volume and frequency during movement
      or the stimulation of certain muscles and joints. This can be evaluated using a
      structured testing method. To be able to easily perceive tinnitus modulations,
      the test must be performed in total silence. Effective treatment modules are
      physiotherapy, osteopathy, neural therapy, and Qigong for self-help.

PMID- 25862619
TI  - Stress and tinnitus.
AB  - Emotional stress is a constant companion of tinnitus patients, since this phantom
      sound can unfortunately be a very effective stressor. However, the mechanism of
      stress contribution to the onset or progression of tinnitus remains unknown.
      Here, we review the pathways induced by emotional stress and the outcome of their
      induction: corticosteroid-dependent changes in gene expression, epigenetic
      modulations, and impact of stress on neuronal plasticity and neurotransmission.
      Using clinical examples, we demonstrate the presence of emotional stress among
      tinnitus patients and we present methods to measure the degree of stress. The
      evidence causally linking emotional stress with tinnitus is still indirect-the
      main difficulty lies in the inaccessibility of human auditory tissues and the
      inability to directly measure tinnitus-induced psychological distress in animal
      models. However, we believe that translational research is the future way of
      filling this gap, finding the answers, and thereby improving both the diagnosis
      and treatment of tinnitus patients. 

PMID- 25862621
TI  - [Tinnitus and psychiatric comorbidities].
AB  - Tinnitus is an auditory phantom phenomenon characterized by the sensation of
      sounds without objectively identifiable sound sources. To date, its causes are
      not well understood. The perceived severity of tinnitus correlates more closely
      to psychological and general health factors than to audiometric parameters.
      Together with limbic structures in the ventral striatum, the prefrontal cortex
      forms an internal "noise cancelling system", which normally helps to block out
      unpleasant sounds, including the tinnitus signal. If this pathway is compromised,
      chronic tinnitus results. Patients with chronic tinnitus show increased
      functional connectivity in corticolimbic pathways. Psychiatric comorbidities are
      common in patients who seek help for tinnitus or hyperacusis. Clinicians need
      valid screening tools in order to identify patients with psychiatric disorders
      and to tailor treatment in a multidisciplinary setting. 

PMID- 25862622
TI  - [Newest therapeutic approaches for chronic tinnitus].
AB  - In the majority of cases, tinnitus derives primarily peripherally, from damage to
      hair cells in the inner ear; suffering and annoyance, however, are caused by
      central cortical processing and functional networks of cerebral plasticity.
      Therefore, new therapeutic approaches aim to influence these structures; whether
      it be directly by magnetic radiation, or via direct or indirect electrical
      stimulation. However, these methods can only be efficient if they can integrate
      and rehabilitate the existing hearing loss. Effective habituation therapies
      consist of hearing therapy, rehabilitation of hearing loss by hearing aids and
      psychosomatic stabilisation. In this review, different therapeutic approaches are
      described and valuated.

PMID- 25862623
TI  - [Cochlear implants and tinnitus].
AB  - The cochlear implant became a very successful method of hearing rehabilitation
      for patients with profound sensorineural hearing loss. The benefits of the CI
      extend beyond the medical success and positively influence social and
      psychosocial areas, reflected by an improved HRQoL. Furthermore, variety of
      studies demonstrated that the tinnitus severity improves in 46-95 % of cases
      following the cochlear implantation. However, the parameters investigated in such
      studies are not always standardized or addressed by validated questionnaires,
      which explains the high outcome variation between the studies. The relationships
      between HRQoL and tinnitus distress before and after cochlear implantation have
      not been well studied. Nevertheless, it is believed that the improvement in HRQoL
      following CI affects particularly tinnitus.However, an existing tinnitus can also
      worsen or occur for the first time after the surgery. Since neither tinnitus
      frequency nor tinnitus loudness correlate with the tinnitus-induced distress, the
      measurement of HRQoL, distress factors, stress reactions and psychiatric
      comorbidities appears to be the meaningful assessment of positive or negative
      effects of CI on tinnitus.Initial studies demonstrated that also patients with
      unilateral hearing loss may benefit from CI supply, as shown by an improvement in
      HRQoL and reduction of tinnitus-induced distress. For those patients, who despite
      CI implantation experience severe tinnitus, there is an option of tinnitus
      specific CI-fitting and tinnitus-specific therapy with psychosomatic and
      psychological approaches, and- in addition- a treatment of possible mental
      comorbidities. 

PMID- 25862624
TI  - Neural substrates of tinnitus in animal and human cortex : cortical correlates of
      tinnitus.
AB  - Animal models of tinnitus complement human findings and potentially deepen our
      insight into the neural substrates of tinnitus. The fact that animal data are
      largely based on recordings from the auditory system, in particular from
      subcortical structures, makes comparison with human electrophysiological data
      from predominantly cortical areas difficult. Electro/magnetoencephalography and
      imaging data extend beyond the auditory cortex. The most challenging link to be
      made is the one between the macroscopic data in humans and the microscopic
      (single neuron action potentials) and mesoscopic (local field potentials) results
      obtained in animal models. Since invasive recordings in humans are rare, a bridge
      needs to be built on the basis of changes in brain rhythms in animals with
      putative tinnitus. 

PMID- 25862625
TI  - Intra-individual variability in tinnitus patients : current thoughts and
      perspectives.
AB  - Most tinnitus studies have attempted to compare groups of individuals, thus
      revealing inter-individuals differences, i.e., variations between compared
      subjects. For methodological reasons, inter-individual studies cannot take into
      account the variability of tinnitus experience, which has been known for decades
      to be relevant in daily practice with tinnitus patients. The concept of intra
      individual variability has been promoted in the research literature, in order to
      shed light on this aspect of individual perception. In previous studies,
      unrelated to hearing, the concept of intra-individual variability implied
      inclusion of the environment (i.e., physical and social interactions) as a factor
      of individual performance. In tinnitus research, we believe that the concept of
      variability (within a person) could find a place beside the concept of variation
      (between groups of subjects). In this paper, four perspectives of tinnitus
      experiences from the clinical and research fields are described: (1) ENT
      consultation; (2) short-term group psychotherapy; (3) psychodynamic
      psychotherapy; and (4) clinical psychological research. Intra-individual
      variability stresses the importance of defining tinnitus in a dynamic way,
      contrary to the current definition of tinnitus as the perception of sound(s). In
      clinical practice, it is useful to embrace the perspective of the perceiver of
      tinnitus, and to include social and cultural circumstances as well as
      audiological/physical changes. 

PMID- 25862626
TI  - 25 years of tinnitus retraining therapy.
AB  - This year marks 25 years of tinnitus retraining therapy (TRT), the approach that
      aims to eliminate tinnitus as a problem by extinguishing functional connections
      between the auditory and the limbic and autonomic nervous systems to achieve
      habituation of tinnitus-evoked reactions and subsequently habituation of
      perception. TRT addresses directly decreased sound tolerance (DST) as well as
      tinnitus. TRT consists of counseling and sound therapy, both based on the
      neurophysiological model of tinnitus. The main goal of retraining counseling is
      to reclassify tinnitus into the category of a neutral stimulus, while the main
      goal of sound therapy is to decrease the strength of tinnitus-related neuronal
      activity. A unique aspect of TRT is that because treatment is aimed to work above
      the tinnitus source, and at connections linking the auditory and other systems in
      the brain, the etiology of tinnitus is irrelevant. Any type of tinnitus, as well
      as somatosounds, can be successfully treated by TRT. Over 100 publications can be
      found on Medline when using "tinnitus retraining therapy" as a search term. The
      majority of these publications indicate TRT offers significant help for about 80
      % of patients. A randomized clinical trial showing the effectiveness of TRT has
      been published and another large study is in progress. The principles of the
      neurophysiological model of tinnitus, and consequently TRT, have not changed in
      over 25 years of use, but a number of changes have been introduced in TRT
      implementation. These changes include the recognition of the importance of
      conditioned reflexes and the dominant role of the subconscious pathways; the
      introduction of the concept of misophonia (i.e., negative reactions to specific
      patterns of sound) and the implementation of specific protocols for its
      treatment; greater emphasis on the concurrent treatment of tinnitus, hyperacusis,
      misophonia, and hearing loss; extensive modification of counseling; and
      refinements in sound therapy. The effectiveness of TRT has increased
      significantly during the past 25 years, presumably due to changes incorporated in
      its implementation. The main improvement has been to shorten the average time
      until seeing clear improvement from 1 year to 1 month, with a statistically
      significant improvement seen at, and after, 3 months. Furthermore, there is a
      higher effectiveness and a shorter treatment time for DST and an increased extent
      of help for hearing loss.

PMID- 25862627
TI  - External ear anomalies and hearing impairment in Noonan Syndrome.
AB  - OBJECTIVE: This is the first cohort in which hearing impairment and external ear
      anomalies in Noonan Syndrome are described extensively. METHODS: Retrospective
      analysis of the otorhinolaryngological and clinical genetic data from 97 Noonan
      Syndrome (NS) patients. Forty-four NS patients were seen by an
      otorhinolaryngologist for the analysis of hearing impairment. In our cohort 80 of
      the 97 patients were genetically tested. In 71 of these mutations were found: in
      48 patients a mutation in PTPN11, in 10 patients in SOS1, in 5 patients in SHOC2,
      in 5 patients in RAF1, in 1 patient in MAP2K2, in 1 patient in KRAS and in 1
      patient in A2ML1. RESULTS: External ear anomalies were reported in 75 NS patients
      (77%). In 69 patients the ears were low-set, 28 patients had posteriorly rotated
      ears, 14 patients showed protruding ears and 18 had thickened helices. Hearing
      impairment was detected in 34 NS patients. Nine patients had sensorineural
      hearing impairment, two a permanent conductive hearing impairment, two other
      patients had mixed hearing impairment and 20 patients had conductive hearing
      impairment in the past, caused by otitis media with effusion. Their temporary
      conductive hearing impairment resolved between the ages of 2 and 18 years.
      Sensorineural hearing impairment varied between mild high-frequency hearing
      impairment and profound (uni- and bilateral) hearing impairment and was
      progressive in three patients. Four NS patients received cochlear implants for
      their severe sensorineural hearing impairment. The cohort is small for genotype
      phenotype correlations, but sensorineural hearing impairment, especially the
      bilateral severe hearing impairment, was only seen in patients with a PTPN11
      mutation. CONCLUSION: NS is characterized by dysmorphic external ear anomalies
      and both sensorineural and conductive hearing impairment. Audiological
      examinations are recommended in all patients with Noonan Syndrome.

PMID- 25862629
TI  - Characteristics and Outcomes of Middle East Respiratory Syndrome Coronavirus
      Patients Admitted to an Intensive Care Unit in Jeddah, Saudi Arabia.
AB  - BACKGROUND: An increasing number of patients are being infected with Middle East
      respiratory syndrome coronavirus (MERS-CoV) since the first case was identified
      in September 2012. We report the characteristics and outcomes of MERS-CoV
      confirmed patients who developed critical illness requiring admission to an
      intensive care unit (ICU). METHODS: We conducted a prospective cohort study of
      all MERS-CoV-confirmed cases who were admitted to our ICU from March 20, 2014,
      till June 1, 2014. Presenting symptoms, comorbid conditions, and details of their
      ICU stay were recorded. RESULTS: Eight patients were admitted to the ICU with
      MERS-CoV infection. All had signs of respiratory distress with 7 requiring
      mechanical ventilation. Three patients were health care workers. In all, 6
      patients had comorbid conditions and 5 patients developed multiorgan system
      failure (MOSF). In all, 5 patients expired, 2 were discharged alive, and 1
      remained intubated at the end of the study period. CONCLUSIONS: Middle East
      respiratory syndrome coronavirus carries a high mortality rate in patients who
      require ICU admission, with a significant number of patients developing MOSF.
      Further investigation is needed to determine optimal management guidelines for
      these patients.

PMID- 25862628
TI  - DNA methylation mediates the effect of maternal smoking during pregnancy on
      birthweight of the offspring.
AB  - BACKGROUND: We examined whether the effect of maternal smoking during pregnancy
      on birthweight of the offspring was mediated by smoking-induced changes to DNA
      methylation in cord blood. METHODS: First, we used cord blood of 129 Dutch
      children exposed to maternal smoking vs 126 unexposed to maternal and paternal
      smoking (53% male) participating in the GECKO Drenthe birth cohort. DNA
      methylation was measured using the Illumina HumanMethylation450 Beadchip. We
      performed an epigenome-wide association study for the association between
      maternal smoking and methylation followed by a mediation analysis of the top
      signals [false-discovery rate (FDR) < 0.05]. We adjusted both analyses for
      maternal age, education, pre-pregnancy BMI, offspring's sex, gestational age and
      white blood cell composition. Secondly, in 175 exposed and 1248 unexposed
      newborns from two independent birth cohorts, we replicated and meta-analysed
      results of eight cytosine-phosphate-guanine (CpG) sites in the GFI1 gene, which
      showed the most robust mediation. Finally, we performed functional network and
      enrichment analysis. RESULTS: We found 35 differentially methylated CpGs (FDR <
      0.05) in newborns exposed vs unexposed to smoking, of which 23 survived
      Bonferroni correction (P < 1 * 10(-7)). These 23 CpGs mapped to eight genes:
      AHRR, GFI1, MYO1G, CYP1A1, NEUROG1, CNTNAP2, FRMD4A and LRP5. We observed partial
      confirmation as three of the eight CpGs in GFI1 replicated. These CpGs partly
      mediated the effect of maternal smoking on birthweight (Sobel P < 0.05) in meta
      analysis of GECKO and the two replication cohorts. Differential methylation of
      these three GFI1 CpGs explained 12-19% of the 202 g lower birthweight in smoking
      mothers. Functional enrichment analysis pointed towards activation of cell
      mediated immunity. CONCLUSIONS: Maternal smoking during pregnancy was associated
      with cord blood methylation differences. We observed a potentially mediating role
      of methylation in the association between maternal smoking during pregnancy and
      birthweight of the offspring. Functional network analysis suggested a role in
      activating the immune system.

PMID- 25862630
TI  - Enhanced sensitivity to sorafenib by inhibition of Akt1 expression in human renal
      cell carcinoma ACHN cells both in vitro and in vivo.
AB  - To investigate whether antitumor activity of sorafenib, a potential molecular
      targeted agent against RCC is enhanced by silencing Akt1 in a human RCC ACHN
      model. We established ACHN in which the expression vector containing short
      hairpin RNA targeting Akt1 was introduced (ACHN/sh-Akt1). Changes in several
      phenotypes of ACHN/sh-Akt1 following treatment with sorafenib were compared with
      those of ACHN transfected with control vector alone (ACHN/C) both in vitro and in
      vivo. When cultured in the standard medium, there was no significant difference
      in the in vitro growth pattern between ACHN/sh-Akt1 and ACHN/C; however, compared
      with ACHN/C, ACHN/sh-Akt1 showed a significantly higher sensitivity to sorafenib.
      Furthermore, treatment with Akt1 inhibitor, A-674563 also resulted in the
      significantly enhanced sensitivity of parental ACHN to sorafenib. Treatment of
      ACHN/sh-Akt1 with sorafenib, but not that of ACHN/C, induced marked
      downregulation of antiapoptotic proteins, including Bcl-2, Bcl-xL, and c-Myc. In
      vivo administration of sorafenib resulted in the significant growth inhibition of
      ACHN/sh-Akt1 tumor compared with that of ACHN/C tumor, and despite the lack of Ki
      67 labeling index between ACHN/sh-Akt1 and ACHN/C tumors, apoptotic index in
      ACHN/sh-Akt1 tumor in mice treated with sorafenib was significantly greater than
      that in ACHN/C tumor. These findings suggest that combined treatment with Akt1
      inhibitor and sorafenib could be a promising therapeutic approach for patients
      with advanced RCC. 

PMID- 25862632
TI  - Parameterization for molecular Gaussian surface and a comparison study of surface
      mesh generation.
AB  - The molecular Gaussian surface has been frequently used in the field of molecular
      modeling and simulation. Typically, the Gaussian surface is defined using two
      controlling parameters; the decay rate and isovalue. Currently, there is a lack
      of studies in which a systematic approach in the determination of optimal
      parameterization according to the geometric features has been done. In this
      paper, surface area, volume enclosed by the surface and Hausdorff distance are
      used as three criteria for the parameterization to make the Gaussian surface
      approximate the solvent excluded surface (SES) well. For each of these three
      criteria, a search of the parameter space is carried out in order to determine
      the optimal parameter values. The resulted parameters are close to each other and
      result in similar calculated molecular properties. Approximation of the VDW
      surface is also done by analyzing the explicit expressions of the Gaussian
      surface and VDW surface, which analysis and parameters can be similarly applied
      to the solvent accessible surface (SAS) due to its geometric similarity to the
      VDW surface. Once the optimal parameters are obtained, we compare the performance
      of our Gaussian surface generation software TMSmesh with other commonly used
      software programs, focusing primarily on mesh quality and fidelity. Additionally,
      the Poisson-Boltzmann solvation energies based on the surface meshes generated by
      TMSmesh and those generated by other software programs are calculated and
      compared for a set of molecules with different sizes. The results of these
      comparisons validate both the accuracy and the applicability of the parameterized
      Gaussian surface. 

PMID- 25862631
TI  - Expression of human kallikrein 1-related peptidase 4 (KLK4) and MET
      phosphorylation in prostate cancer tissue: immunohistochemical analysis.
AB  - Resistance to or relapse after androgen deprivation therapy (ADT) remains a
      significant problem in patients with prostate cancer. Several studies have
      hypothesized that the overexpression of MET and the activating signaling axis in
      prostate cancer cells are associated with castration-resistant prostate cancer
      (CRPC). On the other hand, the expression of human kallikrein 1-related peptidase
      (KLK) 4, which activates plasma HGF activator zymogen, in prostate cancer
      patients with bone metastasis or advanced stage has also been reported. In this
      study, we analyzed the expression and phosphorylation of MET along with KLK4 by
      immunohistochemistry in 62 formalin-fixed paraffin-embedded sections of prostate
      cancer collected by needle biopsy at our hospital between 2006 and 2011. As a
      result, the phosphorylation of MET was observed in 56% (35 of 62 cases) and
      positively correlated with worsening PSA relapse rate in a group of ADT-treated
      patients (P = 0.0445), suggesting significant correlation with CRPC.
      Overexpression of KLK4 was observed in patients with high T stage (P = 0.0001)
      and high Gleason score (P = 0.0146), and the expression was correlated with the
      phosphorylation of MET (P = 0.0002). Pathologically, strong MET phosphorylation
      observed in specific architectures in prostate cancer, such as cribriform
      structures, ill-defined glands or solid patterns, suggested the significance of
      MET activation in promoting the architectural formation of prostate cancer. In
      addition, high positivity rate (80%) of phospho-MET staining at high-grade
      prostatic intraepithelial neoplasia (HGPIN) may indicate the importance of the
      activating signaling axis in the carcinogenesis of prostate cancer.

PMID- 25862633
TI  - Comparison of halogen bonds in M-X?N contacts (M = C, Si, Ge and X = Cl, Br).
AB  - The halogen bonds (XB) formed between some Si-X- and Ge-X- (X is Cl and Br)
      containing molecules and NCH (as a Lewis base) have been investigated and
      compared with C-X?N halogen bond. Although, in all cases, the existence of a
      positive electrostatic potential (sigma-hole) along the extension of M-X was
      responsible for halogen bond formation, multipole expansion of electrostatic
      potential reveals that these positive potentials originate from different atomic
      multipole moments. Indeed, in addition to the monopole moment of M atoms, the
      quadrupole moment of X in C-X molecules, the dipole moment of the halogen in Si-X
      molecules and both the dipole and quadrupole moments of X in Ge-X molecules are
      mainly responsible for the existence of the sigma-hole along the extension of the
      M-X bond. From a different point of view, the distribution of the Laplacian of
      electron density shows that all the studied M-X?N halogen bonds can be regarded
      as "lump-hole" interactions; a region of charge depletion (hole) in the valence
      shell charge concentration (VSCC) of the halogen atom interacts with a region of
      charge concentration (lump) in the VSCC of nitrogen and forms a halogen bond. On
      the other hand, interacting quantum atoms (IQA) analysis of atomic energies
      indicates that, in contrast to C-X?N contacts, in which the interaction between
      halogen and nitrogen is attractive, there is a net repulsive interaction between
      X and N in Si-X?N and Ge-X?N complexes. Indeed, the attraction between Si/Ge and
      nitrogen is mainly responsible for the formation of these halogen bonds. 

PMID- 25862634
TI  - Pre-operative education prior to elective hip arthroplasty surgery improves
      postoperative outcome.
AB  - PURPOSE: Enhanced recovery programmes have improved outcomes following elective
      arthroplasty surgery. There are few studies assessing the role of patient
      education. We therefore assessed the outcomes for patients treated at our unit.
      METHODS: In our enhanced recovery programme, all patients are offered the chance
      to attend a pre-operative education class. Not all patients attend, thus allowing
      comparison of outcomes using our prospectively collected database. RESULTS:
      Between April 2009 and March 2013, 318 patients underwent elective total hip
      replacement (THR): 233 attended the class, and 85 did not. Patients attending had
      a significantly reduced length of stay when compared with nonattenders (3.53 vs
      4.27 days, p = 0.046). This produced cost savings of >L10,000 per year.
      CONCLUSION: Our analysis demonstrates that preoperative education produces
      significantly shorter lengths of stay and cost savings. There are also effects on
      mobilisation and outcome scores. Patients should therefore be encouraged to
      attend these classes.

PMID- 25862635
TI  - Templated misfolding of Tau by prion-like seeding along neuronal connections
      impairs neuronal network function and associated behavioral outcomes in Tau
      transgenic mice.
AB  - Prion-like seeding and propagation of Tau-pathology have been demonstrated
      experimentally and may underlie the stereotyped progression of neurodegenerative
      Tauopathies. However, the involvement of templated misfolding of Tau in neuronal
      network dysfunction and behavioral outcomes remains to be explored in detail.
      Here we analyzed the repercussions of prion-like spreading of Tau-pathology via
      neuronal connections on neuronal network function in TauP301S transgenic mice.
      Spontaneous and GABA(A)R-antagonist-induced neuronal network activity were
      affected following templated Tau-misfolding using synthetic preformed Tau fibrils
      in cultured primary neurons. Electrophysiological analysis in organotypic
      hippocampal slices of Tau transgenic mice demonstrated impaired synaptic
      transmission and impaired long-term potentiation following Tau-seed induced Tau
      aggregation. Intracerebral injection of Tau-seeds in TauP301S mice, caused prion
      like spreading of Tau-pathology through functionally connected neuroanatomical
      pathways. Electrophysiological analysis revealed impaired synaptic plasticity in
      hippocampal CA1 region 6 months after Tau-seeding in entorhinal cortex (EC).
      Furthermore, templated Tau aggregation impaired cognitive function, measured in
      the object recognition test 6 months post-seeding. In contrast, Tau-seeding in
      basal ganglia and subsequent spreading through functionally connected neuronal
      networks involved in motor control, resulted in motoric deficits reflected in
      clasping and impaired inverted grid hanging, not significantly affected following
      Tau-seeding in EC. Immunostaining, biochemical and electron microscopic analysis
      in the different models suggested early pathological forms of Tau, including Tau
      oligomers, rather than fully mature neurofibrillary tangles (NFTs) as culprits of
      neuronal dysfunction. We here demonstrate for the first time using in vitro, ex
      vivo and in vivo models, that prion-like spreading of Tau-misfolding by Tau
      seeds, along unique neuronal connections, causes neuronal network dysfunction and
      associated behavioral dysfunction. Our data highlight the potential relevance of
      this mechanism in the symptomatic progression in Tauopathies. We furthermore
      demonstrate that the initial site of Tau-seeding thereby determines the
      behavioral outcome, potentially underlying the observed heterogeneity in
      (familial) Tauopathies, including in TauP301 mutants.

PMID- 25862636
TI  - Abeta43 is neurotoxic and primes aggregation of Abeta40 in vivo.
AB  - The involvement of Amyloid-beta (Abeta) in the pathogenesis of Alzheimer's
      disease (AD) is well established. However, it is becoming clear that the amyloid
      load in AD brains consists of a heterogeneous mixture of Abeta peptides, implying
      that a thorough understanding of their respective role and toxicity is crucial
      for the development of efficient treatments. Besides the well-studied Abeta40 and
      Abeta42 species, recent data have raised the possibility that Abeta43 peptides
      might be instrumental in AD pathogenesis, because they are frequently observed in
      both dense and diffuse amyloid plaques from human AD brains and are highly
      amyloidogenic in vitro. However, whether Abeta43 is toxic in vivo is currently
      unclear. Using Drosophila transgenic models of amyloid pathology, we show that
      Abeta43 peptides are mainly insoluble and highly toxic in vivo, leading to the
      progressive loss of photoreceptor neurons, altered locomotion and decreased
      lifespan when expressed in the adult fly nervous system. In addition, we
      demonstrate that Abeta43 species are able to trigger the aggregation of the
      typically soluble and non-toxic Abeta40, leading to synergistic toxic effects on
      fly lifespan and climbing ability, further suggesting that Abeta43 peptides could
      act as a nucleating factor in AD brains. Altogether, our study demonstrates high
      pathogenicity of Abeta43 species in vivo and supports the idea that Abeta43
      contributes to the pathological events leading to neurodegeneration in AD. 

PMID- 25862637
TI  - Identification of a novel MET mutation in high-grade glioma resulting in an auto
      active intracellular protein.
AB  - MET has gained interest as a therapeutic target for a number of malignancies
      because of its involvement in tumorigenesis, invasion and metastasis. At present,
      a number of inhibitors, both antibodies against MET or its ligand hepatocyte
      growth factor, and small molecule MET tyrosine kinase inhibitors are in clinical
      trials. We here describe a novel variant of MET that is expressed in 6% of high
      grade gliomas. Characterization of this mutation in a glioma cell line revealed
      that it consists of an intronic deletion, resulting in a splice event connecting
      an intact splice donor site in exon 6 with the next splice acceptor site being
      that of exon 9. The encoded protein lacks parts of the extracellular IPT domains
      1 and 2, encoded by exons 7 and 8, resulting in a novel pseudo-IPT and is named
      MET(Delta7-8). MET(Delta7-8) is located predominantly in the cytosol and is
      constitutively active. The auto-activating nature of MET(Delta7-8), in
      combination with a lack of transmembrane localization, renders MET(Delta7-8) not
      targetable using antibodies, although the protein is efficiently deactivated by
      MET-specific tyrosine kinase inhibitors. Testing of MET-expressing tumors for the
      presence of this variant may be important for treatment decision making.

PMID- 25862639
TI  - Geoengineering as Collective Experimentation.
AB  - Geoengineering is defined as the 'deliberate and large-scale intervention in the
      Earth's climatic system with the aim of reducing global warming'. The
      technological proposals for doing this are highly speculative. Research is at an
      early stage, but there is a strong consensus that technologies would, if
      realisable, have profound and surprising ramifications. Geoengineering would seem
      to be an archetype of technology as social experiment, blurring lines that
      separate research from deployment and scientific knowledge from technological
      artefacts. Looking into the experimental systems of geoengineering, we can see
      the negotiation of what is known and unknown. The paper argues that, in
      renegotiating such systems, we can approach a new mode of governance-collective
      experimentation. This has important ramifications not just for how we imagine
      future geoengineering technologies, but also for how we govern geoengineering
      experiments currently under discussion.

PMID- 25862638
TI  - Intraneuronal APP and extracellular Abeta independently cause dendritic spine
      pathology in transgenic mouse models of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is thought to be caused by accumulation of amyloid-beta
      protein (Abeta), which is a cleavage product of amyloid precursor protein (APP).
      Transgenic mice overexpressing APP have been used to recapitulate amyloid-beta
      pathology. Among them, APP23 and APPswe/PS1deltaE9 (deltaE9) mice are extensively
      studied. APP23 mice express APP with Swedish mutation and develop amyloid plaques
      late in their life, while cognitive deficits are observed in young age. In
      contrast, deltaE9 mice with mutant APP and mutant presenilin-1 develop amyloid
      plaques early but show typical cognitive deficits in old age. To unveil the
      reasons for different progressions of cognitive decline in these commonly used
      mouse models, we analyzed the number and turnover of dendritic spines as
      important structural correlates for learning and memory. Chronic in vivo two
      photon imaging in apical tufts of layer V pyramidal neurons revealed a decreased
      spine density in 4-5-month-old APP23 mice. In age-matched deltaE9 mice, in
      contrast, spine loss was only observed on cortical dendrites that were in close
      proximity to amyloid plaques. In both cases, the reduced spine density was caused
      by decreased spine formation. Interestingly, the patterns of alterations in spine
      morphology differed between these two transgenic mouse models. Moreover, in APP23
      mice, APP was found to accumulate intracellularly and its content was inversely
      correlated with the absolute spine density and the relative number of mushroom
      spines. Collectively, our results suggest that different pathological mechanisms,
      namely an intracellular accumulation of APP or extracellular amyloid plaques, may
      lead to spine abnormalities in young adult APP23 and deltaE9 mice, respectively.
      These distinct features, which may represent very different mechanisms of
      synaptic failure in AD, have to be taken into consideration when translating
      results from animal studies to the human disease.

PMID- 25862640
TI  - Rebamipide Alters the Esophageal Microbiome and Reduces the Incidence of
      Barrett's Esophagus in a Rat Model.
AB  - BACKGROUND: Barrett's esophagus (BE) is characterized by a distinct Th2
      predominant cytokine profile. However, antigens that shift the immune response
      toward the Th2 profile are unknown. AIM: We examined the effects of rebamipide on
      the esophageal microbiome and BE development in a rat model. METHODS: BE was
      induced by esophagojejunostomy in 8-week-old male Wistar rats. Rats were divided
      into control and rebamipide-treated group receiving either a normal or a 0.225 %
      rebamipide-containing diet, respectively, and killed 8, 16, 24, and 32 weeks
      after the operation. PCR-amplified 16S rDNAs extracted from esophageal samples
      were examined by terminal-restriction fragment length polymorphism (T-RFLP)
      analysis to assess microbiome composition. The dynamics of four bacterial genera
      (Lactobacillus, Clostridium, Streptococcus, and Enterococcus) were analyzed by
      real-time PCR. RESULTS: The incidences of BE in the control and rebamipide group
      at 24 and 32 weeks were 80 and 100, and 20 and 33 %, respectively. T-RFLP
      analysis of normal esophagus revealed that the proportion of Clostridium was 8.3
      %, while that of Lactobacillales was 71.8 %. The proportions of Clostridium
      increased and that of Lactobacillales decreased at 8 weeks in both groups. Such
      changes were consistently observed in the control but not in the rebamipide
      group. Clostridium and Lactobacillus expression was lower and higher,
      respectively, in the rebamipide group than in the control group. CONCLUSIONS:
      Rebamipide reduced BE development and altered the esophageal microbiome
      composition, which might play a role in BE development.

PMID- 25862641
TI  - Curcumin Analog L48H37 Prevents Lipopolysaccharide-Induced TLR4 Signaling Pathway
      Activation and Sepsis via Targeting MD2.
AB  - Endotoxin-induced acute inflammatory diseases such as sepsis, mediated by
      excessive production of various proinflammatory cytokines, remain the leading
      cause of mortality in critically ill patients. Lipopolysaccharide (LPS), the
      characteristic endotoxin found in the outer membrane of Gram-negative bacteria,
      can induce the innate immunity system and through the myeloid differentiation
      protein 2 (MD2) and Toll-like receptor 4 (TLR4) complex, increase the production
      of inflammatory mediators. Our previous studies have found that a curcumin
      analog, L48H37 [1-ethyl-3,5-bis(3,4,5-trimethoxybenzylidene)piperidin-4-one], was
      able to inhibit LPS-induced inflammation, particularly tumor necrosis factor
      alpha and interleukin 6 production and gene expression in mouse macrophages. In
      this study, a series of biochemical experiments demonstrate L48H37 specifically
      targets MD2 and inhibits the interaction and signaling transduction of LPS
      TLR4/MD2. L48H37 binds to the hydrophobic region of MD2 pocket and forms hydrogen
      bond interactions with Arg(90) and Tyr(102). Subsequently, L48H37 was shown to
      suppress LPS-induced mitogen-activated protein kinase phosphorylation and nuclear
      factor kappaB activation in macrophages; it also dose dependently inhibits the
      cytokine expression in macrophages and human peripheral blood mononuclear cells
      stimulated by LPS. In LPS-induced septic mice, both pretreatment and treatment
      with L48H37 significantly improved survival and protected lung injury. Taken
      together, this work identified a new MD2 specific inhibitor, L48H37, as a
      potential candidate in the treatment of sepsis. 

PMID- 25862642
TI  - Combination of pharmacophore hypothesis and molecular docking to identify novel
      inhibitors of HCV NS5B polymerase.
AB  - Hepatitis C virus (HCV) infection or HCV-related liver diseases are now shown to
      cause more than 350,000 deaths every year. Adaptability of HCV genome to vary its
      composition and the existence of multiple strains makes it more difficult to
      combat the emergence of drug-resistant HCV infections. Among the HCV polyprotein
      which has both the structural and non-structural regions, the non-structural
      protein NS5B RNA-dependent RNA polymerase (RdRP) mainly mediates the catalytic
      role of RNA replication in conjunction with its viral protein machinery as well
      as host chaperone proteins. Lack of such RNA-dependent RNA polymerase enzyme in
      host had made it an attractive and hotly pursued target for drug discovery
      efforts. Recent drug discovery efforts targeting HCV RdRP have seen success with
      FDA approval for sofosbuvir as a direct-acting antiviral against HCV infection.
      However, variations in drug-binding sites induce drug resistance, and therefore
      targeting allosteric sites could delay the emergence of drug resistance. In this
      study, we focussed on allosteric thumb site II of the non-structural protein NS5B
      RNA-dependent RNA polymerase and developed a five-feature pharmacophore
      hypothesis/model which estimated the experimental activity with a strong
      correlation of 0.971 & 0.944 for training and test sets, respectively. Further,
      the Guner-Henry score of 0.6 suggests that the model was able to discern the
      active and inactive compounds and enrich the true positives during a database
      search. In this study, database search and molecular docking results supported by
      experimental HCV viral replication inhibition assays suggested ligands with best
      fitness to the pharmacophore model dock to the key residues involved in thumbs
      site II, which inhibited the HCV 1b viral replication in sub-micro-molar range.

PMID- 25862643
TI  - Examining the photoprotection hypothesis for adaxial foliar anthocyanin
      accumulation by revisiting comparisons of green- and red-leafed varieties of
      coleus (Solenostemon scutellarioides).
AB  - Although plants rely on light to drive energy production via photosynthesis,
      excess light can be harmful. Plants have evolved photoprotective mechanisms to
      mitigate this threat, including thermal energy dissipation, the most common form
      of which involves de-epoxidized constituents of the xanthophyll cycle
      facilitating the conversion of excess excitation energy to heat. A role in
      photoprotection has also been proposed for red anthocyanins when they accumulate
      near the adaxial leaf surface. Here, we compared the response to experimental
      light stress of a red-leafed (anthocyanin rich) and a green-leafed variety of
      coleus [Solenostemon scutellarioides (L.) Codd], examining chlorophyll
      fluorescence emission and pigment composition. After experimentally imposed
      intense white light, red- and green-leafed coleus exhibited manifestations of
      light stress (decreased photosystem II quantum efficiency) of a similar
      magnitude. This, considered alone, could be interpreted as evidence that
      anthocyanins do not serve a photoprotective role. However, during excess light
      exposure, the green-leafed variety employed a greater level of thermal energy
      dissipation and possessed correspondingly higher xanthophyll cycle pool sizes and
      de-epoxidation states. During exposure to red light, which anthocyanins absorb
      very poorly, levels of thermal energy dissipation did not differ between coleus
      varieties. Taken together, our findings suggest that adaxial anthocyanins
      minimize stress associated with excess light absorption and that the green-leafed
      variety of coleus compensated for its much lower levels of adaxial anthocyanins
      by invoking higher levels of energy dissipation. Thus, anthocyanin accumulation
      should be considered alongside the suite of photoprotective mechanisms employed
      by photosynthetic tissues. 

PMID- 25862644
TI  - Involvement of molecular oxygen in the donor-side photoinhibition of Mn-depleted
      photosystem II membranes.
AB  - It has been shown by Khorobrykh et al. (Biochemistry (Moscow) 67:683-688, 2002);
      Yanykin et al. (Biochim Biophys Acta 1797:516-523, 2010); Khorobrykh et al.
      (Biochemistry 50:10658-10665, 2011) that Mn-depleted photosystem II (PSII)
      membrane fragments are characterized by an enhanced oxygen photoconsumption on
      the donor side of PSII which is accompanied with hydroperoxide formation and it
      was suggested that the events are related to the oxidative photoinhibition of
      PSII. Experimental confirmation of this suggestion is presented in this work. The
      degree of photoinhibition was determined by the loss of the capability of
      exogenous electron donors (Mn(2+) or sodium ascorbate) to the reactivation of
      electron transport [measured by the light-induced changes of chlorophyll
      fluorescence yield (?F)] in Mn-depleted PSII membranes. The transition from
      anaerobic conditions to aerobic ones significantly activated photoinhibition of
      Mn-depleted PSII membranes both in the absence and in the presence of exogenous
      electron acceptor, ferricyanide. The photoinhibition of Mn-depleted PSII
      membranes was suppressed upon the addition of exogenous electron donors (Mn(2+),
      diphenylcarbazide, and ferrocyanide). The addition of superoxide dismutase did
      not affect the photoinhibition of Mn-depleted PSII membranes. It is concluded
      that the interaction of molecular oxygen (rather than superoxide anion radical
      formed on the acceptor side of PSII) with the oxidized components of the donor
      side of PSII reflects the involvement of O2 in the donor-side photoinhibition of
      Mn-depleted PSII membranes. 

PMID- 25862645
TI  - Changes in the Rubisco to photosystem ratio dominates photoacclimation across
      phytoplankton taxa.
AB  - When growth irradiance changes, phytoplankton acclimates by changing allocations
      to cellular components to re-balance their capacity to absorb photons versus
      their capacity to use the electrons from the oxidation of water at photosystem
      II. Published changes in the cellular allocations resulting from photoacclimation
      across algal groups highlight that algae adopt different strategies. We examined
      the photoacclimation of the photosynthetic apparatus of six marine phytoplankters
      under near-natural diel irradiance patterns. For most of the phytoplankters, Chl
      a per structural photosystem II unit decreased with increasing growth irradiance,
      but a parallel decline in optical packaging effect allowed cells to maintain
      their functional absorption cross section serving active photosystem II units
      (sigma PSII). Furthermore, no significant changes were observed in the ratio of
      Chl a per photosystem I. The diatom Skeletonema marinoi proved an exception to
      this pattern as Chl a per photosystem II is stable and Chl a per photosystem I
      slightly decreased with light intensity. A clear decrease in the photosystem
      content per cell was observed for all species except for Thalassiosira oceanica
      and S. marinoi. Rubisco content per cell showed little variation with irradiance
      for most algae, except for a 3-fold increase in S. marinoi. A ~700 % increase in
      the Rubisco:photosystem ratio across species with increasing growth irradiance
      indicates this is a key cellular stoichiometric adjustment to balance photon
      absorption capacity and the carbon reduction capacity. Increasing the
      Rubisco:photosystem ratio occurs through a decrease in the photosystems per cell
      for most of the phytoplankters in this study, except in the case of S. marinoi
      where Rubisco per cell increased. 

PMID- 25862647
TI  - Antibodies to adalimumab are associated with future inflammation in Crohn's
      patients receiving maintenance adalimumab therapy: a post hoc analysis of the
      Karmiris trial.
AB  - INTRODUCTION: Data on immunogenicity to adalimumab (ADL) therapy in patients with
      IBD is limited. We performed additional analyses on the Karmiris cohort using the
      homogeneous mobility shift assay (HMSA) focusing on the inter-relationship of
      serum ADL concentration, antibodies-to-adalimumab (ATA), inflammatory markers and
      sustained response. METHODS: 536 prospectively collected serum samples were
      available for analysis of ADL concentration and ATA using HMSA. We studied the
      role of week 4 serum ADL concentration and immunomodulator (IMM) use on ATA
      formation with a Cox proportional hazards model. Mixed model repeated measures
      analysis was performed to assess the independent effects of serum ADL
      concentration and ATA on C-reactive protein (CRP) and response. RESULTS: ATA was
      detected in 20% of patients after a median of 34 (12.4-60.5) weeks. ATA-positive
      samples correlated with lower serum ADL concentration (p<0.001). Cox regression
      modelling showed that week 4 ADL concentration of <5 ug/mL significantly
      increased the future risk of ATA formation (HR=25.1; 95% CI 5.6 to 111.9;
      p=0.0002) and that IMM co-treatment prevented ATA formation (HR=0.23; 95% CI 0.06
      to 0.86; p=0.0293). Regression modelling showed a negative correlation between
      CRP and ADL concentration (p=0.0001) and a positive one with ATA (p=0.0186). The
      model revealed that both lower serum ADL concentration and ATA were independently
      associated with future CRP (p=0.0213 and p=0.0013 respectively). ATA positivity
      was associated with discontinuation of ADL because of loss or response (OR=3.04;
      95% CI 1.039 to 9.093; p=0.034). CONCLUSIONS: ATA were detected in 20% of
      patients. Risk of ATA formation increased with lower early serum ADL
      concentration and in patients not on IMM. ATA and ADL were strongly associated
      with higher future CRP level and discontinuation of ADL.

PMID- 25862646
TI  - Toward the complete proteome of Synechocystis sp. PCC 6803.
AB  - The proteome of the photosynthetic model organism Synechocystis sp. PCC 6803 has
      been extensively analyzed in the last 15 years for the purpose of identifying
      proteins specifically expressed in subcellular compartments or differentially
      expressed in different environmental or internal conditions. This review
      summarizes the progress achieved so far with the emphasis on the impact of
      different techniques, both in sample preparation and protein identification, on
      the increasing coverage of proteome identification. In addition, this review
      evaluates the current completeness of proteome identification, and provides
      insights on the potential factors that could affect the complete identification
      of the Synechocystis proteome. 

PMID- 25862648
TI  - Membrane transporters in self resistance of Cercospora nicotianae to the
      photoactivated toxin cercosporin.
AB  - The goal of this work is to characterize membrane transporter genes in Cercospora
      fungi required for autoresistance to the photoactivated, active-oxygen-generating
      toxin cercosporin they produce for infection of host plants. Previous studies
      implicated a role for diverse membrane transporters in cercosporin resistance. In
      this study, transporters identified in a subtractive cDNA library between a
      Cercospora nicotianae wild type and a cercosporin-sensitive mutant were
      characterized, including two ABC transporters (CnATR2, CnATR3), an MFS
      transporter (CnMFS2), a uracil transporter, and a zinc transport protein.
      Phylogenetic analysis showed that only CnATR3 clustered with transporters
      previously characterized to be involved in cercosporin resistance. Quantitative
      RT-PCR analysis of gene expression under conditions of cercosporin toxicity,
      however, showed that only CnATR2 was upregulated, thus this gene was selected for
      further characterization. Transformation and expression of CnATR2 in the
      cercosporin-sensitive fungus Neurospora crassa significantly increased
      cercosporin resistance. Targeted gene disruption of CnATR2 in the wild type C.
      nicotianae, however, did not decrease resistance. Expression analysis of other
      transporters in the cnatr2 mutant under conditions of cercosporin toxicity showed
      significant upregulation of the cercosporin facilitator protein gene (CFP),
      encoding an MFS transporter previously characterized as playing an important role
      in cercosporin autoresistance in Cercospora species. We conclude that cercosporin
      autoresistance in Cercospora is mediated by multiple genes, and that the fungus
      compensates for mutations by up-regulation of other resistance genes. CnATR2 may
      be a useful gene, alone or in addition to other known resistance genes, for
      engineering Cercospora resistance in crop plants. 

PMID- 25862650
TI  - The Relationship Between Motor Skills, Social Problems, and ADHD Symptomatology:
      Does It Vary According to Parent and Teacher Report?
AB  - OBJECTIVE: This study investigated the relationship between motor performance;
      attentional, hyperactive, and impulsive symptoms; and social problems.
      Correlations between parents' versus teachers' ratings of social problems and
      ADHD symptomatology were also examined. METHOD: A total of 129 children aged 9 to
      12 years were included. ADHD symptoms and social problems were identified based
      on Conners' Rating Scales-Revised: L, and the McCarron Assessment of
      Neuromuscular Development was used to assess motor skills. RESULTS: After
      controlling for ADHD symptomatology, motor skills remained a significant
      predictor of social problems in the teacher model but not in the parent model.
      After controlling for motor skills, inattentive (not hyperactive-impulsive)
      symptoms were a significant predictor of social problems in the parent model,
      whereas hyperactive-impulsive (not inattentive) symptoms were a significant
      predictor of social problems in the teacher model. CONCLUSION: The findings
      suggested that intervention strategies should consider the interaction between
      symptoms and environmental contexts.

PMID- 25862649
TI  - Ischemia-modified albumin levels in overt and subclinical hypothyroidism.
AB  - BACKGROUND: Free radical-mediated oxidative stress (OS) has been implicated in
      the pathogenesis of thyroid disorders. The ischemia-modified albumin (IMA) has
      been proposed as a marker of protein oxidative damage, which has been found to
      reflect hypoxic stress. AIM: Our aim was to evaluate IMA, malondialdehyde (MDA),
      and reduced glutathione (GSH) levels in patients with overt hypothyroidism (OHT)
      and subclinical hypothyroidism (SHT) in comparison to euthyroid controls.
      SUBJECTS AND METHODS: Albumin, IMA, IMA/albumin ratio, MDA, GSH, total
      cholesterol (TC), triglycerides (TG), HDL-Cholesterol were assessed in 105
      subjects grouped into OHT, SHT patients, and euthyroid controls with 35 subjects
      in each group. RESULTS: MDA and IMA levels were significantly elevated while the
      GSH concentrations were significantly lower in OHT and SHT patients compared to
      controls (p < 0.01). When IMA values were normalized for albumin concentrations,
      the IMA/albumin ratio was also significantly elevated in both patient groups
      compared to controls (p < 0.01). These changes were more pronounced in the OHT
      group when compared to SHT group. In OHT group, thyroid-stimulating hormone (TSH)
      levels showed significant positive correlation with MDA (r = 0.470, p = 0.004),
      IMA (r = 0.530, p = 0.001), and IMA/albumin ratio (r = 0.525, p = 0.001). Both
      IMA (r = -0.342, p = 0.041), IMA/albumin ratio (r = -0.378, p = 0.023) showed
      significant negative correlation with GSH in OHT patients. No significant
      correlation between variables was, however, observed in SHT group. CONCLUSIONS:
      Increase of MDA and IMA levels with decreased antioxidant status indicate the
      presence of OS in hypothyroid patients, which was more pronounced in OHT
      patients. Elevated levels of IMA can be a clinically useful marker of protein
      oxidative damage and OS in hypothyroidism.

PMID- 25862651
TI  - Externalization of a stiff guide wire via the radial artery: a new technique to
      facilitate advancement of an Inoue balloon across the aortic valve in patients
      with aortic stenosis undergoing antegrade balloon aortic valvuloplasty.
AB  - An 84-year-old woman with aortic stenosis underwent antegrade balloon aortic
      valvuloplasty (BAV). After transseptal puncture, we introduced a 7-Fr wedge
      catheter into the left ventricle and across the aortic valve. We then inserted a
      0.032-inch soft guide wire, and the tip of the guide wire was advanced into the
      brachial artery and exchanged for a stiff guide wire. We externalized the tip of
      the stiff guide wire from the radial artery. Finally, we advanced an Inoue
      balloon (Toray, Tokyo, Japan) across the aortic valve and inflated the balloon.
      Transradial externalization makes antegrade BAV an even less invasive procedure. 

PMID- 25862652
TI  - Neurophysiological monitoring during acute and progressive experimentally induced
      compression injury of the spinal cord in pigs.
AB  - PURPOSE: To evaluate the degree of acute or progressive lateral compression
      needed to cause neurologic injury to the spinal cord assessed by
      electrophysiological monitoring. METHODS: In five domestic pigs, the spinal cord
      was exposed and compressed between T8-T9 roots using a precise compression
      device. Two sticks placed on both sides of the spinal cord were sequentially
      brought together (0.5 mm every 2 min), causing progressive spinal cord
      compression. Acute compression was reproduced by a 2.5-mm displacement of the
      sticks. Cord-to-cord evoked potentials were obtained with two epidural catheters.
      RESULTS: Increasing latency and decreasing amplitude of the evoked potentials
      were observed after a mean progressive displacement of the sticks of 3.2 +/- 0.9
      mm, disappearing after a mean displacement of 4.6 +/- 1.2 mm. The potential
      returned after compression removal (16.8 +/- 3.2 min). The potentials disappeared
      immediately after an acute compression of 2.5 +/- 0.3 mm, without any sign of
      recovering after 30 min. CONCLUSIONS: The experimental model replicates the
      mechanism of a spinal cord injury caused by medially displaced screws into the
      spinal canal. The spinal cord had more ability for adaptation to progressive and
      slow compression than to acute mechanisms.

PMID- 25862653
TI  - CT morphometry of adult thoracic intervertebral discs.
AB  - PURPOSE: Despite being commonly affected by degenerative disorders, there are few
      data on normal thoracic intervertebral disc dimensions. A morphometric analysis
      of adult thoracic intervertebral discs was, therefore, undertaken. METHODS:
      Archival computed tomography scans of 128 recently deceased individuals (70
      males, 58 females, 20-79 years) with no known spinal pathology were analysed to
      determine thoracic disc morphometry and variations with disc level, sex and age.
      Reliability was assessed by intraclass correlation coefficients (ICCs). RESULTS:
      Anterior and posterior intervertebral disc heights and axial dimensions were
      significantly greater in men (anterior disc height 4.0+/-1.4 vs 3.6+/-1.3 mm;
      posterior disc height 3.6+/-0.90 vs 3.4+/-0.93 mm; p<0.01). Disc heights and
      axial dimensions at T4-5 were similar or smaller than at T2-3, but thereafter
      increased caudally (mean anterior disc height T4-5 and T10-11, 2.7+/-0.7 and
      5.4+/-1.2 mm, respectively, in men; 2.6+/-0.8 and 5.1+/-1.3 mm, respectively, in
      women; p<0.05). Except at T2-3, anterior disc height decreased with advancing age
      and anteroposterior and transverse disc dimensions increased; posterior and
      middle disc heights and indices of disc shape showed no consistent statistically
      significant changes. Most parameters showed substantial to almost perfect
      agreement for intra- and inter-rater reliability. CONCLUSIONS: Thoracic disc
      morphometry varies significantly and consistently with disc level, sex and age.
      This study provides unique reference data on adult thoracic intervertebral disc
      morphometry, which may be useful when interpreting pathological changes and for
      future biomechanical and functional studies.

PMID- 25862654
TI  - Novel posterior technique to temporize life-threatening hemorrhage after great
      vessel laceration during posterior osteotomy.
AB  - PURPOSE: Great vessel injury during posterior 3-column osteotomy is rare, but
      potentially fatal. Literature review revealed limited data guiding spine surgeons
      during this major catastrophe. In this study our aim was first, to present our
      case of mortality; second, to discuss a novel technique that can be performed to
      temporize hemorrhage in a life-threatening situation where an iatrogenic great
      vessel injury occurs and hemodynamic stability cannot be achieved through usual
      means of hemostasis; third, a cadaveric study to determine if this novel
      technique is feasible. METHODS: Three fresh cadavers including thoracic, lumbar,
      and pelvis were used. A thoraco-abdominal approach was used to access great
      vessels at the level of L3. The aorta and vena cava were identified and tagged.
      The cadavers were turned prone; a pedicle subtraction osteotomy was performed at
      the level of L3. A novel posterior peri-vertebral approach was used to reach the
      great vessels. The aorta and vena cava were occluded digitally with this approach
      and success confirmed visually through the thoraco-abdominal incision. Timing of
      the procedure and structures at risk were recorded. RESULTS: In all three
      cadavers, we were able to successfully occlude the great vessels from a prone
      position. The average amount of time it took to digitally occlude the great
      vessels was less than a minute. Structures at risk included the L1 and L2 nerve
      roots, lumbosacral plexus, and the sympathetic trunk. CONCLUSIONS: The posterior
      peri-vertebral approach can potentially be used by a spine surgeon during a life
      threatening situation to temporarily occlude great vessel hemorrhage while
      waiting for the assistance of a vascular/trauma team.

PMID- 25862655
TI  - Model animals and their applications.

PMID- 25862656
TI  - Protein prenylation and human diseases: a balance of protein farnesylation and
      geranylgeranylation.
AB  - The protein prenylation is one of the essential post-translational protein
      modifications, which extensively exists in the eukaryocyte. It includes protein
      farnesylation and geranylgeranylation, using farnesyl pyrophosphate (FPP) or
      geranylgeranyl pyrophosphate (GGPP) as the substrate, respectively. The
      prenylation occurs by covalent addition of these two types of isoprenoids to
      cysteine residues at or near the carboxyl terminus of the proteins that possess
      CaaX motif, such as Ras small GTPase family. The attachment of hydrophobic prenyl
      groups can anchor the proteins to intracellular membranes and trigger downstream
      cell signaling pathway. Geranylgeranyl biphosphate synthase (GGPPS) catalyzes the
      synthesis of 20-carbon GGPP from 15-carbon FPP. The abnormal expression of this
      enzyme will affect the relative content of FPP and GGPP, and thus disrupts the
      balance between protein farnesylation and geranylgeranylation, which participates
      into various aspects of cellular physiology and pathology. In this paper, we
      mainly review the property of this important protein post-translational
      modification and research progress in its regulation of cigarette smoke induced
      pulmonary disease, adipocyte insulin sensitivity, the inflammation response of
      Sertoli cells, the hepatic lipogenesis and the cardiac hypertrophy. 

PMID- 25862657
TI  - Germ layer formation during Xenopus embryogenesis: the balance between
      pluripotency and differentiation.
AB  - The African clawed frog, Xenopus laevis, has long been a model animal for the
      studies in the fields of animal cloning, developmental biology, biochemistry,
      cell biology, and physiology. With the aid of Xenopus, major molecular mechanisms
      that are involved in embryonic development have been understood. Germ layer
      formation is the first event of embryonic cellular differentiation, which is
      induced by a few key maternal factors and subsequently by zygotic signals.
      Meanwhile, another type of signals, the pluripotency factors in ES cells, which
      maintain the undifferentiated state, are also present during early embryonic
      cells. In this review, the functions of the pluripotency factors during Xenopus
      germ layer formation and the regulatory relationship between the signals that
      promote differentiation and pluripotency factors are discussed. 

PMID- 25862658
TI  - Using zebrafish as the model organism to understand organ regeneration.
AB  - The limited regenerative capacity of several organs, such as central nervous
      system (CNS), heart and limb in mammals makes related major diseases quite
      difficult to recover. Therefore, dissection of the cellular and molecular
      mechanisms underlying organ regeneration is of great scientific and clinical
      interests. Tremendous progression has already been made after extensive
      investigations using several model organisms for decades. Unfortunately, distance
      to the final achievement of the goal still remains. Recently, zebrafish became a
      popular model organism for the deep understanding of regeneration based on its
      powerful regenerative capacity, in particular the organs that are limitedly
      regenerated in mammals. Additionally, zebrafish are endowed with other advantages
      good for the study of organ regeneration. This review summarizes the recent
      progress in the study of zebrafish organ regeneration, in particular regeneration
      of fin, heart, CNS, and liver as the representatives. We also discuss reasons of
      the reduced regenerative capacity in higher vertebrate, the roles of inflammation
      during regeneration, and the difference between organogenesis and regeneration. 

PMID- 25862659
TI  - Glucose metabolic abnormality is associated with defective mineral homeostasis in
      skeletal disorder mouse model.
AB  - Bone was reported as a crucial organ for regulating glucose homeostasis. In this
      study, we found that Phex mutant mice (PUG), a model of human X-linked
      hypophosphatemic rickets (XLH), displayed metabolic abnormality in addition to
      abnormal phosphate homeostasis, skeletal deformity and growth retardation.
      Glucose tolerance was elevated with enhanced insulin sensitivity in PUG, though
      circulating insulin level decreased. Interestingly, bone mineral density defects
      and glucose metabolic abnormality were both rescued by adding phosphorus- and
      calcium-enriched supplements in daily diet. Serum insulin level, glucose
      tolerance and insulin sensitivity showed no differences between PUG and wild-type
      mice with rescued osteocalcin (OCN) following treatment. Our study suggested that
      OCN is a potential mediator between mineral homeostasis and glucose metabolism.
      This investigation brings a new perspective on glucose metabolism regulation
      through skeleton triggered mineral homeostasis and provides new clues in clinical
      therapeutics of potential metabolic disorders in XLH patients. 

PMID- 25862660
TI  - Inactivation of Cipc alters the expression of Per1 but not circadian rhythms in
      mice.
AB  - Circadian clocks are comprised of self-sustained transcriptional/translational
      feedback loops, which regulate the rhythms of physiology and behavior in mammals.
      CLOCK-interacting protein, Circadian (CIPC), has been indicated as an additional
      negative-feedback regulator of the circadian clock in vitro, although its
      physiological roles in circadian clock are unknown. Here, we generated Cipc
      homozygous knockout (Cipc (-/-)) mice and assessed the resultant circadian
      phenotypes. Surprisingly, the mRNA expression profiles of core clock genes in the
      liver of Cipc (-/-) mice showed no significant differences from that in wild-type
      mice except for Per1. Cipc (-/-) mice displayed normal locomotor rhythm and
      entrained activity pattern in both 12:12 light-dark cycle and constant dark
      cycle. Furthermore, deletion of Cipc in lungs and adipose tissues did not
      influence their peripheral clock. The results from this work provided more
      conclusive data suggesting that CIPC is not critically required for basic clock
      function. 

PMID- 25862661
TI  - A bacterial artificial chromosome transgenic mouse model for visualization of
      neurite growth.
AB  - Class III beta-tubulin (Tubb3) is a component of the microtubules in neurons and
      contributes to microtubule dynamics that are required for axon outgrowth and
      guidance during neuronal development. We here report a novel bacterial artificial
      chromosome (BAC) transgenic mouse line that expresses Class III beta-tubulin
      fused to mCherry, an improved monomeric red fluorescent protein, for the
      visualization of microtubules during neuronal development. A BAC containing Tubb3
      gene was modified by insertion of mCherry complementary DNA downstream of Tubb3
      coding sequence via homologous recombination. mCherry fusion protein was
      expressed in the nervous system and testis of the transgenic animal, and the
      fluorescent signal was observed in the neurons that located in the olfactory
      bulb, cerebral cortex, hippocampal formation, cerebellum, as well as the retina.
      Besides, Tubb3-mCherry fusion protein mainly distributed in neurites and
      colocalized with endogenous Class III beta-tubulin. The fusion protein labels
      Purkinje cell dendrites during cerebellar circuit formation. Therefore, this
      transgenic line might be a novel tool for scientific community to study neuronal
      development both in vitro and in vivo. 

PMID- 25862662
TI  - ABO blood type and ABO gene with susceptibility to deep vein thrombosis following
      orthopedic surgery: a case-control study in Chinese Han population.

PMID- 25862663
TI  - Towards a better understanding of mouse and human diseases-International Mouse
      Phenotyping Consortium.

PMID- 25862664
TI  - Growing with the world: rapid development of the zebrafish research in China and
      the China Zebrafish Resource Center.

PMID- 25862665
TI  - Right Atrial Volume is Increased in Corrected Tetralogy of Fallot and Correlates
      with the Incidence of Supraventricular Arrhythmia: A CMR Study.
AB  - The aim of this study was to evaluate right atrial (RA) volume in corrected
      Tetralogy of Fallot (cTOF) and assess its correlation with the occurrence of
      supraventricular (SV) arrhythmia. Cardiac magnetic resonance imaging (CMR) and 24
      h Holter were performed in n = 67 consecutive cTOF patients (age 30 +/- 11.3
      years). The CMR protocol included standard HASTE, SSFP cine, and blood flow
      measurements. Correlations between arrhythmia in ECG, heart volume, and
      functional parameters were investigated by negative binominal regression.
      Patients' characteristics (mean +/- SD) included mean RA volume of 49 +/- 19
      ml/m(2) (HASTE sequence), mean right ventricular (RV) end-diastolic volume of 98
      +/- 27 ml/m(2), mean pulmonary valve regurgitation fraction (PR) of 21 +/- 19 %,
      BMI of 25 kg/m(2), and heart rate of 75/min. Twenty-eight out of 67 patients
      experienced SV arrhythmia including SV couplets or bigeminus or longer non
      sustained SV tachycardia (SVT) episodes. RA volume index was identified as an
      independent risk factor for different degrees of SV arrhythmia (SV
      couplets/bigeminus p < 0.001, SVT p < 0.001). Further risk factors for SV
      arrhythmia were male gender (p = 0.023) and decreased left ventricular (LV)
      ejection fraction (EF) (LV EF p < 0.001). RA volume is increased in adult
      patients with cTOF with larger RA volumes relating to higher incidence of SV
      arrhythmia. SV arrhythmia also appeared more often in male patients and those
      with decreased LV EF. Risk stratification according to these parameters could
      help to optimize early prevention and adjusted individual therapy to improve
      patient outcome and quality of life.

PMID- 25862667
TI  - Intraoperative assistive technologies-the way ahead.

PMID- 25862666
TI  - Does size matter? Decompressive surgery under review.
AB  - In patients with traumatic brain injury (TBI) and ischemic hemispheric stroke
      (IHS), supratentorial decompressive craniectomy (DC) is performed when
      intracranial pressure (ICP) is unresponsive to medical treatment. There are
      numerous publications about the indications of supratentorial DC, the selection
      of patients eligible for surgery, the complications of the procedure, and the
      neurological outcome of operated patients. Only few papers, however, describe
      comprehensively the technical aspects of this procedure. DC consists of a variety
      of steps that can be conducted in different manners. Based on the literature
      reviewed, this article gathers features that had been developed with the intent
      to improve the decompressive effect of this surgery and evaluates if there is a
      strong recommendation for clinical practice. The existing literature does not
      supply class I evidence of how an ideal DC should be designed to reduce peri- and
      postoperative complications and to provide the best functional outcome. 

PMID- 25862668
TI  - Usefulness of a device for body support during operations performed while
      standing.
AB  - During microsurgical procedures, manipulations are often performed using a foot
      switch while the surgeon stands on one foot. This position can easily result in
      body axis instability and greater musculoskeletal loading. To support the
      surgeon's posture, we have developed a tool called the "Surgeon's Body Support
      Device." The objective of this study was to determine the efficacy of this device
      by analyzing surgeons' kinematics and musculoskeletal loading during simulated
      operations undertaken while standing. Fourteen surgeons volunteered to perform
      simulations of surgery while standing. To analyze motion kinetics and
      musculoskeletal loading with and without this device, a three-axis accelerometer
      and surface electromyography (SEMG) sensors were attached to the subjects.
      Compared with not using the supportive device, the axis of the surgeon's body was
      significantly more stable when the support device was used (P = .001). The
      evenness of motion also tended to be superior when the device was utilized (P =
      .009). Simulations performed using the device significantly reduced the
      musculoskeletal loading on the ventral side of the left foot by 70 % compared
      with simulations performed not using the device (P = .001). Data from SEMG sensor
      placed on the right hand, which performs the surgical manipulations, indicated
      that simulations performed using the device generated approximately 10 % of the
      musculoskeletal load generated when the device was not used (P = .001). The
      Surgeon's Body Support Device appears to improve maneuverability and reduce
      musculoskeletal loading during simulated surgical procedures undertaken while
      standing. 

PMID- 25862670
TI  - Are Histological Findings of Thulium Laser Vapo-Enucleation Versus Transurethral
      Resection of the Prostate Comparable?
AB  - We investigated if an adequate histological diagnosis can be made from tissue
      after Thulium laser vapo-enucleation of the prostate (ThuVEP) and whether it is
      comparable to transurethral prostate resection (TURP) tissue findings in patients
      with symptomatic benign prostatic hyperplasia. We analyzed 350 ThuLEP and 100
      matched TURP tissue specimens from patients who underwent one of the two
      procedures between January 2009 and June 2014. Thulium Laser Enucleation of
      Prostate (ThuVEP) was combined with mechanical morcellation of the resected lobe.
      Each histological specimen was reviewed by two pathologists. Preoperative
      prostate ultrasound volume, total serum prostatic specific antigen and
      postoperative tissue weight were evaluated. Microscopic histological diagnosis
      was assessed by standard histological techniques and immunohistochemical
      evaluation. Patients were comparable in terms of age and preoperative total serum
      prostate specific antigen. Incidental adenocarcinoma and high grade PIN of the
      prostate were diagnosed in a comparable percent of specimens in the 2 groups (2.5
      % in the ThuVEP group versus 3 % in the TURP group). Tissue thermal artifacts
      induced by the Thulium laser are mostly due to coagulation as that of the
      conventional monopolar diathermy in TURP. Tissue quality was maintained in the
      ThuVEP histological specimens. Tissue maintain histological characteristics and
      proprieties without modification for successive immunoistochemical analysis. The
      pathologist ability to detect incidental prostate cancer and PIN was maintained
      even if there is a quoted of vaporized tissue.

PMID- 25862669
TI  - Isolation, structural analysis, and expression characteristics of the maize TIFY
      gene family.
AB  - TIFY, previously known as ZIM, comprises a plant-specific family annotated as
      transcription factors that might play important roles in stress response. Despite
      TIFY proteins have been reported in Arabidopsis and rice, a comprehensive and
      systematic survey of ZmTIFY genes has not yet been conducted. To investigate the
      functions of ZmTIFY genes in this family, we isolated and characterized 30 ZmTIFY
      (1 TIFY, 3 ZML, and 26 JAZ) genes in an analysis of the maize (Zea mays L.)
      genome in this study. The 30 ZmTIFY genes were distributed over eight
      chromosomes. Multiple alignment and motif display results indicated that all
      ZmTIFY proteins share two conserved TIFY and Jas domains. Phylogenetic analysis
      revealed that the ZmTIFY family could be divided into two groups. Putative cis
      elements, involved in abiotic stress response, phytohormones, pollen grain, and
      seed development, were detected in the promoters of maize TIFY genes. Microarray
      data showed that the ZmTIFY genes had tissue-specific expression patterns in
      various maize developmental stages and in response to biotic and abiotic
      stresses. The results indicated that ZmTIFY4, 5, 8, 26, and 28 were induced,
      while ZmTIFY16, 13, 24, 27, 18, and 30 were suppressed, by drought stress in the
      maize inbred lines Han21 and Ye478. ZmTIFY1, 19, and 28 were upregulated after
      infection by three pathogens, whereas ZmTIFY4, 13, 21, 23, 24, and 26 were
      suppressed. These results indicate that the ZmTIFY family may have vital roles in
      response to abiotic and biotic stresses. The data presented in this work provide
      vital clues for further investigating the functions of the genes in the ZmTIFY
      family. 

PMID- 25862671
TI  - Cardiovascular risk factors cause premature rarefaction of the collateral
      circulation and greater ischemic tissue injury.
AB  - RATIONALE: Collaterals lessen tissue injury in occlusive disease. However, aging
      causes progressive decline in their number and smaller diameters in those that
      remain (collateral rarefaction), beginning at 16 months of age in mice (i.e.,
      middle age), and worse ischemic injury-effects that are accelerated in even 3
      month-old eNOS(-/-) mice. These findings have found indirect support in recent
      human studies. OBJECTIVE: We sought to determine whether other cardiovascular
      risk factors (CVRFs) associated with endothelial dysfunction cause collateral
      rarefaction, investigate possible mechanisms, and test strategies for prevention.
      METHODS AND RESULTS: Mice with nine different models of CVRFs of 4-12 months of
      age were assessed for number and diameter of native collaterals in skeletal
      muscle and brain and for collateral-dependent perfusion and ischemic injury after
      arterial occlusion. Hypertension caused collateral rarefaction whose severity
      increased with duration and level of hypertension, accompanied by greater
      hindlimb ischemia and cerebral infarct volume. Chronic treatment of wild-type
      mice with L-N (G)-nitro-arginine methylester caused similar rarefaction and worse
      ischemic injury which were not prevented by lowering arterial pressure with
      hydralazine. Metabolic syndrome, hypercholesterolemia, diabetes mellitus, and
      obesity also caused collateral rarefaction. Neither chronic statin treatment nor
      exercise training lessened hypertension-induced rarefaction. CONCLUSION: Chronic
      CVRF presence caused collateral rarefaction and worse ischemic injury, even at
      relatively young ages. Rarefaction was associated with increased proliferation
      rate of collateral endothelial cells, effects that may promote accelerated
      endothelial cell senescence.

PMID- 25862672
TI  - Altered functional connectivity in the brain default-mode network of earthquake
      survivors persists after 2 years despite recovery from anxiety symptoms.
AB  - Although acute impact of traumatic experiences on brain function in disaster
      survivors is similar to that observed in post-traumatic stress disorders (PTSD),
      little is known about the long-term impact of this experience. We have used
      structural and functional magnetic resonance imaging to investigate resting-state
      functional connectivity and gray and white matter (WM) changes occurring in the
      brains of healthy Wenchuan earthquake survivors both 3 weeks and 2 years after
      the disaster. Results show that while functional connectivity changes 3 weeks
      after the disaster involved both frontal-limbic-striatal and default-mode
      networks (DMN), at the 2-year follow-up only changes in the latter persisted,
      despite complete recovery from high initial levels of anxiety. No gray or WM
      volume changes were found at either time point. Taken together, our findings
      provide important new evidence that while altered functional connectivity in the
      frontal-limbic-striatal network may underlie the post-trauma anxiety experienced
      by survivors, parallel changes in the DMN persist despite the apparent absence of
      anxiety symptoms. This suggests that long-term changes occur in neural networks
      involved in core aspects of self-processing, cognitive and emotional functioning
      in disaster survivors which are independent of anxiety symptoms and which may
      also confer increased risk of subsequent development of PTSD. 

PMID- 25862674
TI  - Financial incentives help people change health behaviours, review shows.

PMID- 25862673
TI  - Resting lateralized activity predicts the cortical response and appraisal of
      emotions: an fNIRS study.
AB  - This study explored the effect of lateralized left-right resting brain activity
      on prefrontal cortical responsiveness to emotional cues and on the explicit
      appraisal (stimulus evaluation) of emotions based on their valence. Indeed
      subjective responses to different emotional stimuli should be predicted by brain
      resting activity and should be lateralized and valence-related (positive vs
      negative valence). A hemodynamic measure was considered (functional near-infrared
      spectroscopy). Indeed hemodynamic resting activity and brain response to
      emotional cues were registered when subjects (N = 19) viewed emotional positive
      vs negative stimuli (IAPS). Lateralized index response during resting state, LI
      (lateralized index) during emotional processing and self-assessment manikin
      rating were considered. Regression analysis showed the significant predictive
      effect of resting activity (more left or right lateralized) on both brain
      response and appraisal of emotional cues based on stimuli valence. Moreover,
      significant effects were found as a function of valence (more right response to
      negative stimuli; more left response to positive stimuli) during emotion
      processing. Therefore, resting state may be considered a predictive marker of the
      successive cortical responsiveness to emotions. The significance of resting
      condition for emotional behavior was discussed. 

PMID- 25862675
TI  - F protein increases CD4+CD25+ T cell population in patients with chronic
      hepatitis C.
AB  - HCV is a global health problem with an estimated 230 million chronically infected
      people worldwide. It has been reported that a 17-kd protein translated from core
      encoding genomic region can contribute to immune-mediated mechanisms associated
      with the development of the chronic disease. Also, Treg cells can be contributed
      to an inadequate response against the viruses, leading to chronic infection. Here
      we evaluated the ability of protein F to modulate the frequency of
      CD4+CD25+FoxP3+T and IL-10+T cells in patients with chronic HCV infection. F gene
      was amplified and cloned in the expression vector. The protein was purified and
      used for stimulation of PBMCs in the HCV chronic patients and the control groups.
      The frequency of CD4+CD25+FoxP3+ T cell-like populations and IL-10-producing
      CD4+CD25+ T cells was assessed in the HCV-infected patients and in the healthy
      controls by flow cytometry, which showed an increase of both CD4+CD25+FoxP3+ T
      cell-like population and IL-10-producing CD4+CD25+ T cells in the HCV-infected
      patients positive for anti-F antibody. Our results suggest the potential
      involvement of F and core antigens in increasing the frequency of CD4+CD25+FoxP3+
      T cell-like population and IL-10-producing CD4+CD25+ T cells which may be
      associated with HCV-persistent infection. 

PMID- 25862676
TI  - STAT5 is Activated by Epidermal Growth Factor and Induces Proliferation and
      Invasion in Trophoblastic Cells.
AB  - Epidermal growth factor (EGF) is expressed by decidual and trophoblast cells and
      influences manifold cellular functions during embryo implantation. Thus far,
      signaling of EGF via Signal Transducer and Activator of Transcription 5 (STAT5)
      has been only partially investigated. STAT5 stimulates proliferation and cell
      cycle progression in several cell types. Its dysregulation is associated with
      pregnancy. The aim of this study was to investigate STAT5 activation and function
      mediated by EGF in 2 trophoblastic cell lines, namely, HTR8/SVneo and JAR.
      Additionally, expression of STAT5B messenger RNA (mRNA) in trophoblast models has
      been compared to that of primary cells isolated from term placentas. Our results
      demonstrate the highest STAT5B mRNA expression in isolated trophoblast cells,
      lower expression in HTR8/SVneo cells, and the significantly lowest in JAR cells.
      Moreover, EGF-mediated STAT5 activation increases cell proliferation and
      viability in both cell lines. The STAT5 knockdown results in significant decrease
      in cell viability induced by EGF. Only in HTR8/SVneo cells, invasion decreases
      after STAT5 silencing and this effect cannot be rescued by further addition of
      EGF. These results demonstrate that STAT5 activated by EGF constitutes an
      important cascade for the regulation of cell proliferation and invasion in
      trophoblast cells. 

PMID- 25862677
TI  - Mouse Endometrium Temporal and Spatial Expression mRNA and MicroRNA Associated
      With Embryo Implantation.
AB  - Embryo implantation is a dynamic physiological process involving morphological
      and molecular changes in the endometrium during the pre-receptivity, receptivity,
      and implantation phases. A comprehensive analysis of messenger RNA (mRNA) and
      microRNA (miRNA) profiles during implantation will likely provide new clues to
      elucidate the underlying mechanisms governing embryo implantation. We
      characterized the mRNA and miRNA transcriptomes using next generation sequencing
      (NGS) of the endometrium 1 day postcoitum (dpc) and 4dpc and the implantation
      site (IMS) and inter-implantation (IIM) site of the endometrium on 5dpc. Real
      time quantitative polymerase chain reaction was performed on selected miRNAs and
      their predicted target mRNAs to validate their negatively correlated expression.
      Statistical analysis of the data based on Gene Ontology (GO) group annotation and
      Kyoto Encyclopedia of Genes and Genomes pathway analysis demonstrated that the
      genes with significant expression at the IIM site were primarily involved in
      glucose, protein, and lipoprotein metabolism to provide energy for embryo
      implantation, while the genes identified at the IMS were involved in RNA
      functions to produce proteins in support of embryo development and trophoblast
      invasion. Extracellular matrix (ECM)-receptor interactions between cells and the
      ECM was the most remarkable event during implantation. The miRNA-mRNA interaction
      network unraveled the regulatory relationship between miRNAs and mRNAs. Hub
      miRNAs (mmu-miR-96 and mmu-miR-200b) were identified to target B-cell lymphoma 2
      (Bcl-2), Kruppel-like factor 13 (Klf13), and Progesterone receptor (PGR), which
      are associated with the preparation of the receptive condition or the maintenance
      of early pregnancy. 

PMID- 25862678
TI  - Uncertainty in sample estimates: sampling error.

PMID- 25862679
TI  - Multiple cold resistance loci confer the high cold tolerance adaptation of
      Dongxiang wild rice (Oryza rufipogon) to its high-latitude habitat.
AB  - KEY MESSAGE: Dongxiang wild rice is phylogenetically close to temperate japonica
      and contains multiple cold resistance loci conferring its adaptation to high
      latitude habitat. Understanding the nature of adaptation in wild populations will
      benefit crop breeding in the development of climate-resilient crop varieties.
      Dongxiang wild rice (DXWR), the northernmost common wild rice known, possesses a
      high degree of cold tolerance and can survive overwintering in its native
      habitat. However, to date, it is still unclear how DXWR evolved to cope with low
      temperature environment, resulting in limited application of DXWR in rice
      breeding programs. In this study, we carried out both QTL mapping and
      phylogenetic analysis to discern the genetic mechanism underlying the strong cold
      resistance. Through a combination of interval mapping and single locus analysis
      in two genetic populations, at least 13 QTLs for seedling cold tolerance were
      identified in DXWR. A phylogenetic study using both genome-wide InDel markers and
      markers associated with cold tolerance loci reveals that DXWR belongs to the Or
      III group, which is most closely related to cold-tolerant Japonica rice rather
      than to the Indica cultivars that are predominant in the habitat where DXWR
      grows. Our study paves the way toward an understanding of the nature of
      adaptation to a northern habitat in O. rufipogon. The QTLs identified in DXWR in
      this study will be useful for molecular breeding of cold-tolerant rice.

PMID- 25862680
TI  - Chromosomal genomics facilitates fine mapping of a Russian wheat aphid resistance
      gene.
AB  - KEY MESSAGE: Making use of wheat chromosomal resources, we developed 11 gene
      associated markers for the region of interest, which allowed reducing gene
      interval and spanning it by four BAC clones. Positional gene cloning and targeted
      marker development in bread wheat are hampered by high complexity and polyploidy
      of its nuclear genome. Aiming to clone a Russian wheat aphid resistance gene
      Dn2401 located on wheat chromosome arm 7DS, we have developed a strategy
      overcoming problems due to polyploidy and enabling efficient development of gene
      associated markers from the region of interest. We employed information gathered
      by GenomeZipper, a synteny-based tool combining sequence data of rice,
      Brachypodium, sorghum and barley, and took advantage of a high-density linkage
      map of Aegilops tauschii. To ensure genome- and locus-specificity of markers, we
      made use of survey sequence assemblies of isolated wheat chromosomes 7A, 7B and
      7D. Despite the low level of polymorphism of the wheat D subgenome, our approach
      allowed us to add in an efficient and cost-effective manner 11 new gene
      associated markers in the Dn2401 region and narrow down the target interval to
      0.83 cM. Screening 7DS-specific BAC library with the flanking markers revealed a
      contig of four BAC clones that span the Dn2401 region in wheat cultivar 'Chinese
      Spring'. With the availability of sequence assemblies and GenomeZippers for each
      of the wheat chromosome arms, the proposed strategy can be applied for focused
      marker development in any region of the wheat genome.

PMID- 25862681
TI  - Weight control behaviors among emerging adults with type 1 diabetes.
AB  - PURPOSE: The purpose of this study was to examine the association of weight
      control behaviors (WCBs) with living and educational situations among emerging
      adults with type 1 diabetes during the first year after high school graduation.
      METHODS: Among 184 emerging adults with type 1 diabetes, data were collected
      every 3 months for 12 months on WCBs, body mass index (BMI), living and
      educational situations; at baseline and 12 months, on impulse control; and at
      baseline, on sex, depressive symptoms, and glycemic control. Generalized linear
      models incorporated repeated measures (0, 3, 6, 9, and 12 months). RESULTS: No
      significant associations existed between WCBs and living or educational
      situations, when controlling for covariates. More depressive symptoms and higher
      BMIs were associated with a greater likelihood of involvement in unhealthy WCBs,
      whereas more depressive symptoms-not higher BMI-were associated with higher odds
      for involvement in very unhealthy WCBs. Although healthy WCBs were also
      associated with more depressive symptoms and higher BMIs, they were also
      associated with greater impulse control. CONCLUSIONS: Health care professionals
      should assess emerging adults with type 1 diabetes for WCBs along with BMI,
      depressive symptoms, and impulse control.

PMID- 25862683
TI  - Biosensors for Monitoring Airborne Pathogens.
AB  - Airborne pathogens affect both humans and animals and are often highly and
      rapidly transmittable. Many problematic airborne pathogens, both viral (influenza
      A/H1N1, Rubella, and avian influenza/H5N1) and bacterial (Mycobacterium
      tuberculosis, Streptococcus pneumoniae, and Bacillus anthracis), have huge
      impacts on health care and agricultural applications, and can potentially be used
      as bioterrorism agents. Many different laboratory-based methods have been
      introduced and are currently being used. However, such detection is generally
      limited by sample collection, including nasal swabs and blood analysis. Direct
      identification from air (specifically, aerosol samples) would be ideal, but such
      detection has not been very successful due to the difficulty in sample collection
      and the extremely low pathogen concentration found in aerosol samples. In this
      review, we will discuss the portable biosensors and/or micro total analysis
      systems (uTAS) that can be used for monitoring such airborne pathogens, similar
      to smoke detectors. Current laboratory-based methods will be reviewed, and
      possible solutions to convert these lab-based methods into uTAS biosensors will
      be discussed. 

PMID- 25862682
TI  - Multiple mutations and increased RNA expression in tetracycline-resistant
      Streptococcus pneumoniae as determined by genome-wide DNA and mRNA sequencing.
AB  - OBJECTIVES: The objective of this study was to characterize chromosomal mutations
      associated with resistance to tetracycline in Streptococcus pneumoniae. METHODS:
      Chronological appearance of mutations in two S. pneumoniae R6 mutants (R6M1TC-5
      and R6M2TC-4) selected for resistance to tetracycline was determined by next
      generation sequencing. A role for the mutations identified was confirmed by
      reconstructing resistance to tetracycline in a S. pneumoniae R6 WT background.
      RNA sequencing was performed on R6M1TC-5 and R6M2TC-4 and the relative expression
      of genes was reported according to R6. Differentially expressed genes were
      classified according to their ontology. RESULTS: WGS of R6M1TC-5 and R6M2TC-4
      revealed mutations in the gene rpsJ coding for the ribosomal protein S10 and in
      the promoter region and coding sequences of the ABC genes patA and patB. These
      cells were cross-resistant to ciprofloxacin. Resistance reconstruction confirmed
      a role in resistance for the mutations in rpsJ and patA. Overexpression of the
      ABC transporter PatA/PatB or mutations in the coding sequence of patA contributed
      to resistance to tetracycline, ciprofloxacin and ethidium bromide, and was
      associated with a decreased accumulation of [(3)H]tetracycline. Comparative
      transcriptome profiling of the resistant mutants further revealed that, in
      addition to the overexpression of patA and patB, several genes of the thiamine
      biosynthesis and salvage pathway were increased in the two mutants, but also in
      clinical isolates resistant to tetracycline. This overexpression most likely
      contributes to the tetracycline resistance phenotype. CONCLUSIONS: The
      combination of genomic and transcriptomic analysis coupled to functional studies
      has allowed the discovery of novel tetracycline resistance mutations in S.
      pneumoniae.

PMID- 25862684
TI  - Independent risk factors associated with hospital-acquired pneumonia in an adult
      ICU: 4-year prospective cohort study in a university reference hospital.
AB  - BACKGROUND: Hospital-acquired pneumonia (HP) is the most common infection in
      adult intensive care units (ICUs). To develop effective strategies to prevent it,
      we identified factors that independently increased the risk of contracting HP
      while admitted at an ICU. METHODS: We performed a prospective cohort study during
      4 years in which we included all patients who had been admitted for at least 24 h
      to the ICU at a university reference hospital in Spain. We conducted a
      multivariable Cox regression analysis to obtain adjusted hazard ratios (HR). The
      dependent variable for patients with HP was duration of ICU stay prior to the
      onset of HP. For those without HP, the dependent variable was duration of stay
      between admission and discharge from the ICU. The independent variables were
      intrinsic characteristics of the patients already present at admission to the ICU
      and diagnostic or therapeutic procedures performed during admission. RESULTS: We
      studied 4427 patients, of which 233 (5.3%) developed HP while admitted to the
      ICU. The strongest independent risk factors associated with the occurrence of HP
      were mechanical ventilation (HR = 8.2; 95% CI = 3.6-18.9) and the use of a
      nasogastric tube (HR = 2.3; 95% CI = 1.6-3.3). The intrinsic risk factors that
      were part of the model were the presence of decreased level of consciousness upon
      admission (HR = 2.0; 95% CI = 1.5-2.7) and the APACHE II index (HR = 1.018; 95%
      CI = 1.002-1.035). CONCLUSIONS: Although severity of illness upon admission
      (APACHE II index) and decreased level of consciousness were relevant predisposing
      factors to contract HP in the ICU, the strongest association corresponded to
      extrinsic factors such as mechanical ventilation and use of a nasogastric tube.
      The fact that these are therapeutic interventions facilitates developing
      prevention and control measures that can contribute to reduce the risk for HP.

PMID- 25862685
TI  - A Phenotypic High-Throughput Screen with RSV-Infected Primary Human Small Airway
      Epithelial Cells (SAECs).
AB  - Respiratory syncytial virus (RSV) is a commonly occurring pathogen that can cause
      severe disease in children, the elderly, and immunocompromised individuals with a
      large, unmet clinical need. We developed a high-throughput, primary cell-based
      antiviral RSV assay to enable identification of small molecules using cytopathic
      effect (CPE) as a phenotypic end point. To provide increased biological
      relevance, we developed our assay with primary human small airway epithelial
      cells (SAECs), which originate from known sites of RSV infection and replication
      instead of a more traditional immortalized cell line. Using purchased low-passage
      cells, cost-effective large-scale culture methods were developed to provide assay
      ready frozen SAECs. A high-throughput screening campaign using the GSK Screening
      Collection was performed. The screen was executed in 384-well plates over a 12
      week period with an average Z' of 0.5. The screen yielded 17 post-entry hits with
      activity in the primary cells, which were not active in immortalized cells.
      Potencies for this class of compounds were equal between the primary and
      immortalize cell lines. For entry inhibitors, the number was much lower, with
      increased potency observed in immortalized cells. This is the first known use of
      frozen primary human cells for an RSV high-throughput screening phenotypic
      campaign. 

PMID- 25862686
TI  - Genetic factors play a role in risk of sexual offending, study finds.

PMID- 25862688
TI  - Recent developments in understanding the iron acquisition strategies of gram
      positive pathogens.
AB  - Iron is a versatile redox-active catalyst and a required cofactor within a
      diverse array of biological processes. To almost all organisms, iron is both
      essential and potentially toxic, where homeostatic concentrations must be
      stringently maintained. Within the iron-restricted host, the survival and
      proliferation of microbial invaders is contingent upon exploiting the host iron
      pool. Bacteria express a multitude of complex, and often redundant means of
      acquiring iron, including surface-associated heme-uptake pathways, high affinity
      iron-scavenging siderophores and transporters of free inorganic iron. Within the
      last decade, our understanding of iron acquisition by Gram-positive pathogens has
      expanded substantively, from the discovery of the iron-regulated surface
      determinant pathway and numerous unique siderophores through to the detailed
      elucidation of heme-iron extraction, and heme and siderophore coordination and
      transfer. This review provides a comprehensive summary of the iron acquisition
      strategies of notorious Gram-positive pathogens and highlights how both conserved
      and distinct tactics for acquiring iron contribute to the pathophysiology of
      these bacteria. Further, a focus on recent structural and mechanistic studies
      details how these iron acquisition systems may be exploited in the development of
      novel therapeutics. 

PMID- 25862689
TI  - Bacterial membrane lipids: diversity in structures and pathways.
AB  - For many decades, Escherichia coli was the main model organism for the study of
      bacterial membrane lipids. The results obtained served as a blueprint for
      membrane lipid biochemistry, but it is clear now that there is no such thing as a
      typical bacterial membrane lipid composition. Different bacterial species display
      different membrane compositions and even the membrane composition of cells
      belonging to a single species is not constant, but depends on the environmental
      conditions to which the cells are exposed. Bacterial membranes present a large
      diversity of amphiphilic lipids, including the common phospholipids
      phosphatidylglycerol, phosphatidylethanolamine and cardiolipin, the less frequent
      phospholipids phosphatidylcholine, and phosphatidylinositol and a variety of
      other membrane lipids, such as for example ornithine lipids, glycolipids,
      sphingolipids or hopanoids among others. In this review, we give an overview
      about the membrane lipid structures known in bacteria, the different metabolic
      pathways involved in their formation, and the distribution of membrane lipids and
      metabolic pathways across taxonomical groups. 

PMID- 25862690
TI  - Obama warns of climate change threat to public health.

PMID- 25862691
TI  - A rapid anion-exchange chromatography for measurement of cholesterol
      concentrations in five lipoprotein classes and estimation of lipoprotein profiles
      in male volunteers without overt diseases.
AB  - BACKGROUND: Analysis of lipoprotein profile gives important clinical information
      for lipid-lowering therapy which prevents atherosclerotic diseases. The
      lipoprotein classes can be isolated from serum with ultracentrifugation, which
      inevitably consumes a long time and needs large serum volume. We have established
      a method with anion-exchange chromatography with 1.0 uL of the injected volume in
      5.2 min for assay of one sample. METHODS: One-hundred-forty-one male volunteers
      without overt diseases were divided three groups (Group 1, non-dyslipidemia with
      LDL-cholesterol [LDL-C] <120 mg/dL and HDL-cholesterol (HDL-C) >=40 mg/dL; Group
      2, borderline dyslipidemia with 120 <= LDL-C < 140 mg/dL and HDL-C >=40 mg/dL;
      Group 3, dyslipidemia with LDL-C >= 140 mg/dL or HDL-C < 40 mg/dL). Their
      lipoprotein profiles were evaluated by rapid anion-exchange chromatography, which
      measured concentrations of HDL-C, LDL-C, IDL-cholesterol, VLDL-cholesterol, and
      other fraction (chylomicron + lipoprotein [a])-cholesterol (other-C). RESULTS:
      The within-day and between-day assay coefficients of variation of lipoprotein
      cholesterol values were 0.33-4.31% and 2.37-9.19%, respectively. The correlation
      coefficients between values of HDL-C, LDL-C, IDL-C and VLDL-C by the anion
      exchange chromatography and those by ultracentrifugal method were 0.97, 0.92,
      0.58 and 0.94, respectively. Group 3 had significantly lower HDL-C and higher
      concentrations of IDL-C, VLDL-C and other-C than did Group 1. Group 2, borderline
      dyslipidemia, had significantly higher concentrations of IDL-C and VLDL-C than
      did Group 1. CONCLUSION: The rapid anion-exchange chromatography assay may be
      sufficiently applied to the assessment of borderline dyslipidemia.

PMID- 25862692
TI  - The Influence of Stress, Gender, and Culture on Type 2 Diabetes Prevention and
      Management Among Black Men: A Qualitative Analysis.
AB  - This study used focus-group methodology to seek understanding about the unique
      influence of stress, gender, and culture on type 2 diabetes mellitus (t2dm)
      prevention and management among Black men. Twenty men from Iowa were recruited
      from a larger longitudinal study on Black families; each of these men
      participated in one of three focus groups. Ninety-five percent of the men in the
      sample were Black and all were either diagnosed with t2dm (n = 10), were
      prediabetic (n = 1), or had experience with t2dm through family and friends (n =
      9). Our results revealed the existence of significant stress and some pessimism
      with respect to perceived ability to prevent and manage t2dm. The participants
      made it clear that, while their families are primary sources of support for
      managing stress, including t2dm, they can also be a source of stress,
      particularly with respect to parenting. Black men had mixed opinions on their
      relationships with respect to their health care providers; some had positive,
      long-standing relationships while others reported little or no relationship with
      their providers. In response to life stress, Black men reported experiencing
      inadequate and disrupted sleep as well as consuming too much alcohol at times.
      Some of the participants reported engaging in physical activity to manage their
      stress. The study concluded that, as researchers develop t2dm prevention and
      management programs, they should continue to consider the unique role that stress
      in its various forms, plays in the lives of Black men. 

PMID- 25862693
TI  - Perceptions of Health-Related Quality of Life: A Minority Men's Perspective.
AB  - Health-related quality of life (HRQOL) measures among the African American
      populations have previously been inadequately studied. This study sought to
      further analyze the quality of life of African American men at the Cleveland
      Clinic Minority Men's Health Center and Cleveland Clinic Minority Men's Health
      Fair. Subjects were randomly selected at the Minority Health Fair and Minority
      Men's Health Center clinics over the duration of 2 weeks to participate in the
      anonymous survey with the help of independent surveyors. Convenience sampling was
      done at the Minority Men's Health Fair and at the Minority Men's Health Clinics.
      Participants were administered in-person Short Form-36 (SF-36v2). A total of 83
      participants were surveyed, and the response rate from the surveyed population
      was 100%. The only exclusion criterion for the study was the refusal to
      participate ( n = 0). As compared with healthy U.S. norms, African American men
      reported lower HRQOL across six health domains: physical functioning (60.69 +/-
      2.82 vs. 84.2), general health (57.56 +/- 2.41 vs. 72), social functioning (72.65
      +/- 3.17 vs. 83.3), role-emotional (55.89 +/- 3.02 vs. 81.3), mental health
      (61.23 +/- 2.34 vs. 74.7), and role-physical (62.5 +/- 2.88 vs. 81). The largest
      difference between the health domains was reported in role limitations due to
      emotional problems (55.89 +/- 3.02 vs. 81.3, 25.4). Marital analysis revealed
      clinically significant lower HRQOL in married African Americans as compared with
      nonmarried, statistically significant in physical functioning and physical health
      component ( p < .05). African Americans disproportionally face pervasive
      disparities in health, as supported by extensive quality of life impairment. No
      other study, to our knowledge, has used quality of life assessment in African
      Americans to quantitate how such disparities are affecting important domains in
      their lives.

PMID- 25862695
TI  - Photo quiz: A 50-year-old woman with fever, rash, and polyarthritis.

PMID- 25862694
TI  - Differences in Obesity Among Men of Diverse Racial and Ethnic Background.
AB  - Racial/ethnic disparities exist in obesity prevalence among men, with Hispanic
      men exhibiting the highest prevalence compared with non-Hispanic White and non
      Hispanic Black men. Most studies do not parse out Hispanic groups; therefore, it
      is unclear whether the increases in obesity rates among Hispanic men applies to
      all groups or if there are particular groups of Hispanic men that are driving the
      increase. The goal of this study is to examine the variations in obesity among
      men of diverse racial/ethnic backgrounds and determine if obesity is affected by
      nativity. The data used in this study were from 11 years (2002-2012) of the
      National Health Interview Survey. Logistic regression was used to examine the
      relationship between race/ethnicity, obesity, and nativity. After adjusting for
      covariates, there are differences in obesity prevalence, with the largest
      prevalence among Puerto Rican men and Mexican American men. Consistent with
      previous literature, it has been suggested that men born in the United States are
      more likely to be obese than men born outside the United States. This study
      underscores the importance of distinguishing Hispanic groups when examining
      obesity, and provides information for future, targeted intervention strategies
      related to obesity among high-risk groups.

PMID- 25862697
TI  - Indian anti-tobacco campaigners plead for larger graphic warnings on products.

PMID- 25862698
TI  - A laser-plasma-produced soft X-ray laser at 89 eV generates DNA double-strand
      breaks in human cancer cells.
AB  - While it has been expected that X-ray laser will be widely applied to biomedical
      studies, this has not been achieved to date and its biological effects such as
      DNA damage have not been evaluated. As a first step for its biological
      application, we developed a culture cell irradiation system, particularly
      designed for a plasma-driven soft X-ray laser pulse, to investigate whether the
      soft X-ray laser is able to induce DNA double strand breaks (DSBs) in living
      cells or not. The human adenocarcimona cell line A549 was irradiated with the
      soft X-ray laser at a photon energy of 89 eV and the repair focus formation of
      the DSBs was assessed by immunofluorescence staining with antiphosphorylated DNA
      PKcs (p-DNA-PKcs), ATM (p-ATM) and gamma-H2AX antibody. The p-DNA-PKcs, ATM, and
      gamma-H2AX foci were clearly identified after soft X-ray laser irradiation.
      Furthermore, the increase in the X-ray laser shot number, even from a single
      shot, results in the increase in p-DNA-PKcs foci. These results are the first
      evidence that the 89 eV soft X-ray laser is able to induce DSB in living cells.
      Our study demonstrated that this irradiation system is a useful tool for
      investigating the radiobiological effect of soft X-ray laser. 

PMID- 25862699
TI  - A surveillance study of intensity-modulated radiation therapy for postoperative
      cervical cancer in Japan.
AB  - Intensity-modulated radiation therapy (IMRT) was recently introduced to the field
      of gynecologic malignancies; however, its value is not yet validated. A clinical
      trial is in preparation to investigate the efficacy and feasibility of IMRT for
      postoperative cervical cancer. The object of this study was to perform a
      surveillance study of IMRT for post-operative cervical cancer. A questionnaire
      regarding the precise methods of conducting IMRT was sent to six institutions
      that had already introduced IMRT for post-operative cervical cancer, and the data
      were analyzed. Half of the institutions used static IMRT and the others used
      volumetric-modulated arc therapy (VMAT). Most institutions used body-immobilizing
      devices for patient fixation. Most institutions instructed patients to fill their
      bladder before undergoing planning CT or daily treatment. While one institution
      inserted metallic markers and another one used radio-contrast-soaked gauze to
      visualize the vaginal cuff, the other institutions used nothing for vaginal cuff
      visualization. Most institutions defined the clinical target volumes according to
      the Japan Clinical Oncology Group or the Radiation Therapy Oncology Group
      guidelines. Only one institution used a prescribed dose based on 95% of the PTV
      (D(95)), while the rest used the mean dose (D(mean)). This valuable information
      from six leading institutions will be utilized in a future prospective clinical
      trial.

PMID- 25862700
TI  - Public health activities for mitigation of radiation exposures and risk
      communication challenges after the Fukushima nuclear accident.
AB  - Herein we summarize the public health actions taken to mitigate exposure of the
      public to radiation after the Fukushima accident that occurred on 11 March 2011
      in order to record valuable lessons learned for disaster preparedness.
      Evacuations from the radiation-affected areas and control of the distribution of
      various food products contributed to the reduction of external and internal
      radiation exposure resulting from the Fukushima incident. However, risk
      communication is also an important issue during the emergency response effort and
      subsequent phases of dealiing with a nuclear disaster. To assist with their
      healing process, sound, reliable scientific information should continue to be
      disseminated to the radiation-affected communities via two-way communication. We
      will describe the essential public health actions following a nuclear disaster
      for the early, intermediate and late phases that will be useful for radiological
      preparedness planning in response to other nuclear or radiological disasters. 

PMID- 25862701
TI  - The Juvenile Sex Offender.
AB  - In this article, we investigate whether the life events of marriage, parenthood,
      and employment were associated with general offending for a Dutch sample of 498
      juvenile sex offenders (JSOs). In previous empirical studies, these life events
      were found to limit adult general offending in the population as well as high
      risk samples. A hybrid random effects model is used to investigate within
      individual changes of these life events in association with general offending. We
      also investigated whether the findings differed for child abusers, peer abusers,
      and group offenders, as they have distinct background profiles. We found that
      JSOs make limited transitions into the state of marriage, parenthood, and
      employment, showing overall stagnating participation rates. For the entire sample
      of JSOs, employment was found to be associated with a decrease in offending.
      Group offenders benefited most from employment. Marriage and parenthood were not
      associated with the general offending patterns, whereas for child abusers,
      parenthood was associated with an increase in offending. We conclude that
      policies aimed at guidance toward employment, or inclusion into conventional
      society, may be effective for JSOs.

PMID- 25862702
TI  - Management of carbapenem resistant Klebsiella pneumoniae infections in stem cell
      transplant recipients: an Italian multidisciplinary consensus statement.

PMID- 25862703
TI  - Repeat course of rabbit antithymocyte globulin as salvage following initial
      therapy with rabbit antithymocyte globulin in acquired aplastic anemia.

PMID- 25862704
TI  - Targeting the spliceosome in chronic lymphocytic leukemia with the macrolides FD
      895 and pladienolide-B.
AB  - RNA splicing plays a fundamental role in human biology. Its relevance in cancer
      is rapidly emerging as demonstrated by spliceosome mutations that determine the
      prognosis of patients with hematologic malignancies. We report studies using FD
      895 and pladienolide-B in primary leukemia cells derived from patients with
      chronic lymphocytic leukemia and leukemia-lymphoma cell lines. We found that FD
      895 and pladienolide-B induce an early pattern of mRNA intron retention -
      spliceosome modulation. This process was associated with apoptosis preferentially
      in cancer cells as compared to normal lymphocytes. The pro-apoptotic activity of
      these compounds was observed regardless of poor prognostic factors such as
      Del(17p), TP53 or SF3B1 mutations and was able to overcome the protective effect
      of culture conditions that resemble the tumor microenvironment. In addition, the
      activity of these compounds was observed not only in vitro but also in vivo using
      the A20 lymphoma murine model. Overall, these findings give evidence for the
      first time that spliceosome modulation is a valid target in chronic lymphocytic
      leukemia and provide an additional rationale for the development of spliceosome
      modulators for cancer therapy. 

PMID- 25862706
TI  - Postgraduate medical education: the same, but different.

PMID- 25862705
TI  - Fine tuning of surface CRLF2 expression and its associated signaling profile in
      childhood B-cell precursor acute lymphoblastic leukemia.

PMID- 25862707
TI  - Republished: A straightforward guide to the basic science behind
      arrhythmogenesis.
AB  - The underlying mechanisms behind cardiac arrhythmias are described in this
      manuscript. In clinical practice, significant arrhythmias are unpredictable, and
      under some conditions, potentially life-threatening. How can basic science help
      improve our understanding of molecular entities and factors behind the arrhythmia
      to advance, develop, adapt or deliver available medications? Structural heart
      disease and remodelling (e.g., heart failure, cardiomyopathy), the presence of
      modulating factors (i.e., diabetes mellitus, autonomic nervous system), genetic
      predispositions (i.e., channelopathies) are considerable preconditions, and
      influence the development of an arrhythmia. Cardiac arrhythmias may indeed share
      common basic mechanisms, while elements and substrates perpetuating these may be
      different and ultimately manifest as various ECG abnormalities. This article
      lists cellular and subcellular iatrogenic disorders responsible for abnormal
      impulse generation, or conduction disturbances, including the latest development
      in theories and biological research, for a better understanding of cellular
      disorders behind arrhythmogenesis.

PMID- 25862708
TI  - Republished curriculum based clinical review: IBD: reproductive health, pregnancy
      and lactation.
AB  - The peak incidence of inflammatory bowel diseases (IBD) occurs during the child
      bearing years, and so questions about fertility, pregnancy and breast feeding are
      often asked by patients. It is known that patients with IBD receive twice as much
      information about pregnancy-related issues from gastroenterologists as from any
      other source (including the internet). Therefore, the role of the
      gastroenterologist in correctly educating patients to avoid misconceptions is
      paramount, and this should be done proactively prior to planning pregnancy so
      that the patient's health and medications can be optimised. A clear understanding
      of medication safety during pregnancy and lactation will improve clinical
      management. 

PMID- 25862709
TI  - Micro-medullary thyroid carcinoma: a diagnosis not to be missed.

PMID- 25862710
TI  - Medicine under capitalism.

PMID- 25862711
TI  - DOG1 is a sensitive and specific immunohistochemical marker for diagnosis of
      canine gastrointestinal stromal tumors.
AB  - Gastrointestinal stromal tumors (GISTs) and leiomyosarcomas are histologically
      similar primary neoplasms commonly occurring in the gastrointestinal tract of
      dogs and humans. Immunohistochemical staining (IHC) is needed to differentiate
      between these 2 entities and positive reactivity for KIT (cluster of
      differentiation [CD]117) is regarded as the gold standard for diagnosis of canine
      GIST. Studies estimate 5-10% of human GISTs stain negative or only weakly
      positive for KIT and have identified DOG1 (discovered on gastrointestinal stromal
      tumors protein 1) as a highly sensitive and specific marker for human GISTs. The
      purpose of this study was to evaluate immunoreactivity of a commercially
      available DOG1 antibody for use in diagnosis of canine GISTs. Fifty-five primary
      mesenchymal gastrointestinal tumors with histologic features consistent with GIST
      or leiomyosarcoma were evaluated via IHC for KIT, DOG1, and desmin. A subset of
      tumors was additionally evaluated for reactivity for smooth muscle actin (SMA).
      Thirty-three tumors (60%) were diagnosed as GIST based on positive
      immunoreactivity for KIT or DOG1 regardless of reactivity for desmin or SMA. Most
      GISTs (32/33, 97.0%) had similar staining for both KIT and DOG1. DOG1 expression
      was identified in 2 tumors (1 study tumor and 1 additional tumor) negative for
      KIT and desmin that had histologic features consistent with KIT-negative,
      platelet-derived growth factor receptor-alpha (PDGFRA)-mutant human GISTs. Our
      results suggest that DOG1 has improved specificity and sensitivity to that of KIT
      for differentiating between canine GISTs and leiomyosarcomas. Inclusion of both
      DOG1 and KIT IHC in diagnostic panels will improve the accuracy of canine GIST
      diagnosis.

PMID- 25862712
TI  - Detection of Aleutian mink disease virus DNA and antiviral antibodies in American
      mink (Neovison vison) 10 days postinoculation.
AB  - Early detection of infection by the Aleutian mink disease virus (AMDV; Carnivore
      amdoparvovirus 1) by polymerase chain reaction (PCR) or
      counterimmunoelectrophoresis (CIEP) has important ramifications in virus
      eradication programs. A spleen homogenate containing a local isolate of AMDV was
      injected intraperitoneally into black (n = 44) and sapphire (n = 12) American
      mink (Neovison vison). Animals were euthanized 10 days postinoculation and anti
      AMDV antibodies and AMDV DNA were tested in plasma and 7 organs by CIEP and PCR,
      respectively. Viral DNA was detected in the plasma, spleen, lymph nodes, bone
      marrow, and lung samples of all inoculated mink, but was not detected in some
      small intestine, kidney, and liver samples. In contrast, antibodies were detected
      in the plasma of 3 sapphire (25.0%) and 19 black (43.2%) mink but not in any of
      the organs. The sensitivity of the CIEP test on plasma samples was 39.3%,
      implying that low levels of antibodies during the early stages of virus exposure
      resulted in failure to detect infection by the CIEP test. We concluded that CIEP
      is not a reliable test for early detection of AMDV infection in mink and that
      there were considerable differences among mink of each color type for production
      of detectable levels of antibodies. PCR tests on samples of saliva, rectal swabs,
      and feces did not produce consistent and reliable results.

PMID- 25862713
TI  - Microlichus americanus acariasis in saffron finches (Sicalis flaveola) with
      dermatitis and feather loss.
AB  - Over a 5-year period, 13 saffron finches (Sicalis flaveola) housed in mixed
      aviaries at the Bronx Zoo (Bronx, New York) were examined with feather loss and
      dermatitis, primarily affecting the nape, neck, and dorsum. Feather loss,
      hyperkeratosis, epidermal hyperplasia, and mixed granulocytic and mononuclear
      inflammation were identified in biopsies from live birds and tissue sections from
      postmortem specimens. In 10 of 13 cases, sections of arthropod parasites were
      seen histologically within feather follicles and along the surface of affected
      skin. Based on morphological characteristics, mites recovered from samples of
      formalin-fixed skin in 4 birds were identified as Microlichus americanus, an
      epidermoptid mite infrequently reported from wild birds and hippoboscid flies.
      Gross and histological lesions strongly implicate M. americanus as the cause of
      dermatitis affecting practically all saffron finches in the collection. 

PMID- 25862714
TI  - Comparison of trace mineral concentrations in tail hair, body hair, blood, and
      liver of mule deer (Odocoileus hemionus) in California.
AB  - Measuring trace mineral concentrations can be an important component of assessing
      the health of free-ranging deer. Trace mineral concentrations in liver most
      accurately reflect the trace mineral status of an individual, but, in live
      animals, whole blood or serum are the most commonly used sample types. Trace
      minerals measured in serum, such as copper, zinc, and iron, do not always
      accurately correlate to liver concentrations, and supplementary samples for
      evaluating the trace mineral status in live deer would be useful. We evaluated
      the utility of body and tail hair for measuring selenium, copper, zinc, iron, and
      manganese in free-ranging mule deer (Odocoileus hemionus) by using Spearman rank
      correlations and linear regression. Correlations were strongest at the time of or
      shortly after growth of the winter coat and in resident deer. In live deer,
      strong correlations and moderate linear associations (R (2) = 0.57) were detected
      between body and tail hair and whole blood selenium in December. In postmortem
      sampled deer, a strong correlation and linear association (R (2) = 0.80) were
      found between liver and body hair selenium in August-November. Results indicate
      that body hair, if collected during or shortly after growth of the winter coat,
      can be used as a supplementary sample for measuring selenium concentrations in
      deer. None of the other correlations and linear associations were found to be
      sufficiently strong to conclude that hair can reliably be utilized as a
      complementary sample for measuring these trace mineral concentrations.

PMID- 25862715
TI  - Psychosocial Strength Enhancing Resilience in Adolescents and Young Adults With
      Cancer.
AB  - The purpose of this study was to explore ways of enhancing psychosocial strengths
      in newly diagnosed and relapsed adolescents and young adults (AYAs) to improve
      their resilience. A descriptive case study was used. The adolescent resilience
      model (ARM) and the self-sustaining process model were applied as theories. The
      data were analyzed using pattern-matching logic. Semistructured interviews were
      conducted with 18 patients aged 12 to 24 years and discharged within 10 years. We
      found that the newly diagnosed and the relapsing AYAs developed the 5 strength
      factors of the ARM during and after treatment. Whether the individuals cultivated
      a positive attitude and sense of purpose early or late, the AYAs developed
      resilience eventually. A positive attitude and sense of purpose during the early
      phase of care may be essential for improving resilience. The AYAs benefited from
      the support of their parents, friends, and previous experience. Individualized
      support and social resources may be important to develop these strengths. Further
      research is needed to develop strengths and improve resilience in newly diagnosed
      AYAs. 

PMID- 25862716
TI  - Incremental value of left atrial structural and functional characteristics for
      prediction of atrial fibrillation in patients receiving cardiac pacing.
AB  - BACKGROUND: Better prediction of cardiac pacing patients at risk of atrial
      fibrillation (AF) would enable more effective prophylaxis. We sought whether left
      atrial (LA) electromechanical conduction time (EMT) and myocardial mechanics were
      associated with incident AF in patients undergoing dual chamber pacemaker
      implantation, independent of left atrial volume (LAV). METHODS AND RESULTS:
      Clinical data were obtained prospectively in 146 enrollees (73+/-10 years)
      undergoing dual chamber pacemaker implantation in the Protect-Pace study.
      Echocardiograms and 2-dimensional strain analysis were obtained post implantation
      and at 2 years. Complete ascertainment of AF during follow-up was identified from
      interrogation of permanent pacemakers. Cox regression was used to identify
      correlates of AF. Incident AF (n=29, 20%) was associated with higher systolic
      blood pressure (P=0.01), lower left ventricular ejection fraction (P=0.03), lower
      LA strain at atrial contraction (LASac; P<0.001), higher LAV (P<0.003), and
      longer septal electromechanical conduction time (P<0.01). The associations of LAV
      and LASac with incident AF were independent of age, sex, systolic blood pressure,
      and left ventricular size and function. However, the combination of the 3
      strongest predictors showed LASac (P=0.02) and systolic blood pressure (P=0.01)
      were independently associated with incident AF, but LAV was not (P=0.07). Using
      the optimal cut points from receiver operator characteristic curves (62 mL for
      LAV and 8.6% for LASac), we demonstrated that a significantly greater rate of AF
      was associated with both lower LASac at higher LAV and with lower LASac at lower
      LAV. CONCLUSIONS: The risk of AF in patients receiving dual chamber pacing is
      independently associated with LA size and function, not left ventricular
      structural and functional characteristics or right ventricular lead location.
      CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique
      identifier: NCT00461734.

PMID- 25862717
TI  - Long-Term Natural Outcome (7-26 Years) of Lichtman Stage III Kienbock's
      Lunatomalacia.
AB  - BACKGROUND AND AIMS: The natural history of Kienbock's disease is controversial.
      Only three papers report a pure natural history without treatment. We
      hypothesized that the natural course of Kienbock's disease may be better than
      reported. MATERIAL AND METHODS: We examined eight patients with Lichtman stage
      III Kienbock's disease without any treatment, evaluating clinical and
      radiological results (9 wrists; 7 men, mean age at onset of symptoms 34 years)
      over a period of 10-38 years (mean, 27.3 years) after symptom onset. RESULTS:
      Lichtman stage remained the same in five of nine wrists. The inner structure of
      the lunate improved in three, remained the same in three, and deteriorated in
      three wrists, and its shape improved in two, remained the same in four, and
      deteriorated in three wrists. Pain averaged visual analog scale 3.1 at rest, 3.4
      during motion, 3.6 with slight, and 5.2 with heavy exertion. The range of motion
      improved at extension 19% and at flexion 14%, reaching 81% and 72% of that of the
      contralateral wrist, and grip strength reaching 93%. The Disabilities of the Arm,
      Shoulder, and Hand averaged 11.3, Optional Disabilities of the Arm, Shoulder, and
      Hand 18.0, and Mayo Clinic score 70.0. The radiographic course did not correlate
      with clinical course. CONCLUSIONS: The long-term natural history of Lichtman
      stage III Kienbock's disease is insufficiently good to suggest thoughtful
      observation alone as an option to treat it.

PMID- 25862724
TI  - National survey of umbilical venous catheterisation practices in the wake of two
      deaths.

PMID- 25862725
TI  - Rotavirus vaccination in preterm infants: a neonatal guidance chart to aid timely
      immunisation.

PMID- 25862726
TI  - Measurements from preterm infants to guide face mask size.
AB  - OBJECTIVE: International guidelines recommend that an appropriately sized face
      mask for providing positive pressure ventilation should cover the mouth and nose
      but not the eyes and should not overlap the chin. This study aimed to measure the
      dimensions of preterm infants' faces and compare these with the size of the most
      commonly available face masks (external diameter 50 mm) and the smallest masks
      available (external diameters 35 and 42 mm). METHODS: Infants 24-33 weeks'
      postmenstrual age (PMA) were photographed in a standardised manner. Images were
      analysed using ImageJ software (National Institute of Health, USA) to calculate
      the distance from the nasofrontal groove to the mental protuberance. This facial
      measurement corresponds to the external diameter of an optimally fitting mask.
      RESULTS: A cohort of 107 infants between 24 and 33 weeks' gestational age,
      including at least 10 infants per week of gestation, was photographed within 72 h
      after birth and weekly until 33 weeks' PMA. 347 photographs were analysed.
      Infants of 24, 26, 28, 30 and 32 weeks' PMA had mean (SD) facial measurements of
      32 (2), 36 (3), 38 (4), 41 (2) and 43 (4) mm, respectively. There were no
      significant differences when examined by gender or when small for gestational age
      infants were excluded. CONCLUSIONS: The smallest size of some brands of mask is
      too large for many preterm infants. Masks of 35 mm diameter are suitable for
      infants <29 weeks' PMA or 1000 g. Masks of 42 mm diameter are suitable for
      infants 27-33 weeks' PMA or 750-2500 g.

PMID- 25862727
TI  - Marijuana in the Workplace: Guidance for Occupational Health Professionals and
      Employers: Joint Guidance Statement of the American Association of Occupational
      Health Nurses and the American College of Occupational and Environmental
      Medicine.
AB  - Employers are often put in a difficult position trying to accommodate state laws
      that allow the use of marijuana for medical purposes while enforcing federal
      rules or company drug-use policies based on federal law. To ensure workplace
      safety as well as compliance with state and federal legislation, employers should
      review state laws on discrimination against marijuana users and ensure that
      policies enacted are consistent with the state's antidiscrimination statutes.
      Although it appears that in most states that allow medical marijuana use,
      employers can continue enforcing policies banning or restricting the use of
      marijuana, this approach may change on the basis of future court decisions. The
      Joint Task Force recommends that marijuana use be closely monitored for all
      employees in safety-sensitive positions, whether or not covered by federal drug
      testing regulations. Best practice would support employers prohibiting marijuana
      use at work. Employers, in compliance with applicable state laws, may choose to
      simply prohibit their employees from working while using or impaired by
      marijuana. In some states, employers may choose to prohibit marijuana use by all
      members of their workforce whether on or off duty. Nevertheless, in all cases, a
      clear policy to guide decisions on when marijuana use is allowed and how to
      evaluate for impairment must be widely distributed and carefully explained to all
      workers. Legal consultation during policy development and continual review is
      imperative to ensure compliance with federal, state, and case law. Drug-use and
      drug-testing policies should clearly delineate expectations regarding on-the-job
      impairment and marijuana use outside of work hours. Specific criteria for use by
      supervisors and HR personnel when referring employees suspected of impairment for
      an evaluation by a qualified occupational health professional are critical.
      Detailed actions based on the medical evaluation results must also be clearly
      delineated for HRs, supervisors, and workers. The Joint Task Force recommends
      that employers review the following points when developing workplace policies
      that address marijuana use in the workplace: 1. For employees covered by federal
      drug testing regulations (eg, DOT and other workers under federal contract),
      marijuana use, both on or off the job, is prohibited. Thus, employers may use
      urine drug screening in this population. 2. Employees in safety-sensitive
      positions must not be impaired at work by any substance, whether it be illicit,
      legally prescribed, or available over-the-counter. Employers may consider
      prohibiting on the job marijuana use for all employees in safety-sensitive
      positions, even when not covered by federal drug testing regulations.
      Nevertheless, legal review of the employer's policy in the context of state
      statutes is strongly encouraged. When employers allow medical marijuana use by
      employees, consultation with a qualified occupational health professional is
      recommended. 3. Employers residing in or near states that allow the use of
      recreational marijuana must establish a policy regarding off-work use of
      marijuana. In many states, the employer may choose to prohibit employees from
      simply working while using or under the influence of marijuana or may choose to
      prohibit marijuana use both on and off the job. Urine drug testing above
      traditional cutoff levels, or serum testing at any level, would be reasonable
      criteria for the employer wishing to ban both on- and off-the-job use. To detect
      impairment, a limit of 5 ng/mL of THC measured in serum or plasma as THC (or
      possibly the sum of THC plus THC-OH for employers who choose to evaluate both
      psychoactive components) would meet the goal of identifying individuals most
      likely to be impaired. Nevertheless, employers using the 5 ng/ml level need to
      understand the limitations of using a single number to fit all cases; therefore,
      a medical examination focused on identifying impairment is always recommended.
      Legal consultation is strongly recommended. 4. Although it appears that in most
      states that allow the use of medical marijuana, employers may be able to continue
      policies banning or restricting the use of marijuana as previously discussed,
      this practice may change on the basis of future case law. Currently the ADA does
      not apply in these situations because marijuana is illegal under federal law.
      Legal consultation is again strongly recommended. 5. Most workers' compensation
      statutes allow reduced benefits when a worker is under the influence of alcohol
      or illegal drugs. Two samples should usually be obtained as a second confirmatory
      test may be needed. Proof of use and/or impairment is usually required for these
      cases, and a positive urine drug test (for the inactive metabolite) does not
      prove acute impairment. The serum level of less than 5 ng/mL could be used for
      presumptive evidence of impairment in these situations. An MRO is most helpful in
      helping determine these types of cases because legal testimony may be required.
      6. All employers should have clear policies and procedures for supervisors to
      follow regarding the criteria for identifying potential impairment and the
      process for referring an employee suspected of impairment for an occupational
      medical evaluation. Policies should include action required by HR personnel based
      on the results of the examination. 7. Employee education is vital to ensure
      compliance with company expectations. Education is needed at hire and again at
      regular intervals. Workers must know the company's chemical substance policy and
      management's expectations for adherence. The employer's commitment to a drug-free
      workplace and existing company policy will influence the education program's
      content. At a minimum, employees should learn how chemical substances affect
      their health, safety, personal behavior, and job performance. Supervisors and
      employees should also be educated about how to recognize behaviors indicative of
      impairment, whether the source is medical marijuana, prescription medications,
      illegal drugs, alcohol, over-the-counter medications, fatigue, or any combination
      thereof. 8. In states where marijuana use is permitted, employers should provide
      educational resources regarding the detrimental effects of marijuana use,
      including caution regarding dose and delayed effects of edible products. This
      information may be obtained from SAMHSA and state governmental agencies. The
      safety of workers and the public must be central to all workplace policies and
      employers must clearly articulate that legalization of marijuana for recreational
      or medical use does not negate workplace policies for safe job performance. The
      evolving legal situation on medical and recreational marijuana requires employers
      to consult with legal experts to craft company policy and clarify implications of
      impaired on-duty workers. This changing environment surrounding marijuana use
      requires close collaboration between employers, occupational health
      professionals, and legal experts to ensure that workplace safety is not
      compromised.

PMID- 25862728
TI  - A Novel Function for Arabidopsis CYCLASE1 in Programmed Cell Death Revealed by
      Isobaric Tags for Relative and Absolute Quantitation (iTRAQ) Analysis of
      Extracellular Matrix Proteins.
AB  - Programmed cell death is essential for plant development and stress adaptation. A
      detailed understanding of the signal transduction pathways that regulate plant
      programmed cell death requires identification of the underpinning protein
      networks. Here, we have used a protagonist and antagonist of programmed cell
      death triggered by fumonisin B1 as probes to identify key cell death regulatory
      proteins in Arabidopsis. Our hypothesis was that changes in the abundance of cell
      death-regulatory proteins induced by the protagonist should be blocked or
      attenuated by concurrent treatment with the antagonist. We focused on proteins
      present in the mobile phase of the extracellular matrix on the basis that they
      are important for cell-cell communications during growth and stress-adaptive
      responses. Salicylic acid, a plant hormone that promotes programmed cell death,
      and exogenous ATP, which can block fumonisin B1-induced cell death, were used to
      treat Arabidopsis cell suspension cultures prior to isobaric-tagged relative and
      absolute quantitation analysis of secreted proteins. A total of 33 proteins,
      whose response to salicylic acid was suppressed by ATP, were identified as
      putative cell death-regulatory proteins. Among these was CYCLASE1, which was
      selected for further analysis using reverse genetics. Plants in which CYCLASE1
      gene expression was knocked out by insertion of a transfer-DNA sequence
      manifested dramatically increased cell death when exposed to fumonisin B1 or a
      bacterial pathogen that triggers the defensive hypersensitive cell death.
      Although pathogen inoculation altered CYCLASE1 gene expression, multiplication of
      bacterial pathogens was indistinguishable between wild type and CYCLASE1 knockout
      plants. However, remarkably severe chlorosis symptoms developed on gene knockout
      plants in response to inoculation with either a virulent bacterial pathogen or a
      disabled mutant that is incapable of causing disease in wild type plants. These
      results show that CYCLASE1, which had no known function hitherto, is a negative
      regulator of cell death and regulates pathogen-induced symptom development in
      Arabidopsis. 

PMID- 25862729
TI  - Simultaneous Enrichment of Plasma Soluble and Extracellular Vesicular
      Glycoproteins Using Prolonged Ultracentrifugation-Electrostatic Repulsion
      hydrophilic Interaction Chromatography (PUC-ERLIC) Approach.
AB  - Plasma glycoproteins and extracellular vesicles represent excellent sources of
      disease biomarkers, but laboratory detection of these circulating structures are
      limited by their relatively low abundance in complex biological fluids. Although
      intensive research has led to the development of effective methods for the
      enrichment and isolation of either plasma glycoproteins or extracellular vesicles
      from clinical materials, at present it is not possible to enrich both structures
      simultaneously from individual patient sample, a method that affords the
      identification of biomarker combinations from both entities for the prediction of
      clinical outcomes will be clinically useful. We have therefore developed an
      enrichment method for use in mass spectrometry-based proteomic profiling that
      couples prolonged ultracentrifugation with electrostatic repulsion-hydrophilic
      interaction chromatography, to facilitate the recovery of both glycoproteins and
      extracellular vesicles from nondepleted human plasma. Following prolonged
      ultracentrifugation, plasma glycoproteins and extracellular vesicles were
      concentrated as a yellow suspension, and simultaneous analyses of low abundant
      secretory and vesicular glycoproteins was achieved in a single LC-MS/MS run.
      Using this systematic prolonged ultracentrifugation-electrostatic repulsion
      hydrophilic interaction chromatography approach, we identified a total of 127
      plasma glycoproteins at a high level of confidence (FDR <= 1%), including 48
      glycoproteins with concentrations ranging from pg to ng/ml. The novel enrichment
      method we report should facilitate future human plasma-based proteome and
      glycoproteome that will identify novel biomarkers, or combinations of secreted
      and vesicle-derived biomarkers, that can be used to predict clinical outcomes in
      human patients. 

PMID- 25862730
TI  - Impairment of quality of life in patients with antiphospholipid syndrome.
AB  - OBJECTIVES: Health-related quality of life (HRQoL) has not been fully explored in
      antiphospholipid syndrome (APS); therefore, we compared HRQoL between APS
      patients and the general population and assessed the impact of thromboembolic
      history. METHODS: HRQoL was measured in a multicentre cohort study by the Medical
      Outcomes Study Short-Form 36 (MOS-SF-36) questionnaire. HRQoL scores were
      compared to the French general population norms. Factors significantly associated
      with an impaired HRQoL were identified. RESULTS: A total of 115 patients with aPL
      and/or systemic lupus erythematosus (SLE) were included (mean age 42.7 +/- 14.1
      years old, 86 women). In 53 patients APS was diagnosed. Compared to general
      population norms, patients with APS had an impaired HRQoL. SLE-associated APS
      patients had the worst HRQoL scores (physical component summary (PCS)=40.8 +/-
      10.6; mental component summary (MCS)=40.6 +/- 16.5) in comparison with SLE or aPL
      patients without thromboembolic history. In APS patients, history of arterial
      thrombosis significantly impaired HRQoL (PCS score: 42.2 +/- 9.4 vs 49.2 +/- 8.5;
      MCS score: 33.9 +/- 13.7 vs 44.6 +/- 10.3). CONCLUSION: Compared to the general
      population, APS patients experienced a lower HRQoL. In these patients, a history
      of arterial thrombosis significantly impaired HRQoL. Therefore, measurements of
      HRQoL should be included in APS patient management to assess the burden of the
      disease from a patient's perspective and to provide patients with the support
      they need.

PMID- 25862731
TI  - Two decades of maternity care fee exemption policies in Ghana: have they
      benefited the poor?
AB  - OBJECTIVE: To investigate, the impact of maternity-related fee payment policies
      on the uptake of skilled birth care amongst the poor in Ghana. METHODS:
      Population data representing 12 288 births between November 1990 and October 2008
      from four consecutive rounds of the Ghana demographic and health surveys were
      used to examine the impact of four major maternity-related payment policies: the
      full-cost recovery 'cash and carry' scheme; 'antenatal care fee exemption';
      'delivery care fee exemption' and the 'National Health Insurance Scheme (NHIS)'.
      Concentration curves were used to analyse the rich-poor gap in the use of skilled
      birth care by the four policy interventions. Multilevel logistic regression was
      used to examine the effect of the policies on the uptake of skilled birth care,
      adjusting for relevant predictors and clustering within communities and
      districts. FINDINGS: The uptake of skilled birth care over the policy periods for
      the poorest women was trivial when compared with their non-poor counterparts. The
      rich-poor gap in skilled birth care use was highly pronounced during the 'cash
      and carry' and 'free antenatal care' policies period. The benefits during the
      'free delivery care' and ' NHIS' policy periods accrued more for the rich than
      the poor. There exist significant differences in skilled birth care use between
      and within communities and districts, even after adjusting for policy effects and
      other relevant predictors. CONCLUSIONS: The maternal care fee exemption policies
      specifically targeted towards the poorest women had limited impact on the uptake
      of skilled birth care.

PMID- 25862732
TI  - Towards subsidized malaria rapid diagnostic tests. Lessons learned from
      programmes to subsidise artemisinin-based combination therapies in the private
      sector: a review.
AB  - The idea of a private sector subsidy programme of artemisinin-based combination
      therapies (ACTs) was first proposed in 2004. Since then, several countries around
      the world have hosted pilot projects or programmes on subsidized ACTs and/or the
      Affordable Medicines Facility-malaria programme (AMFm). Overall the private
      sector subsidy programmes of ACTs have been effective in increasing availability
      of ACTs in the private sector and driving down average prices but struggled to
      crowd out antimalarial monotherapies. The results obtained from this ambitious
      strategy should inform policy makers in the designing of future interventions
      aimed to control malaria morbidity and mortality. Among the interventions
      recently proposed, a subsidy of rapid diagnostic tests (RDTs) in the private
      sector has been recommended by governments and international donors to cope with
      over-treatment with ACTs and to delay the emergence of resistance to artemisinin.
      In order to improve the cost-effectiveness of co-paid RDTs, we should build on
      the lessons we learned from almost 10 years of private sector subsidy programmes
      of ACTs in malaria-endemic countries. 

PMID- 25862733
TI  - Parkinson's disease and the skin.
AB  - The concept that the skin is a mirror of Parkinson's disease dates to the start
      of the last century. Despite dermatological disorders being recognised as a
      common non-motor symptom of Parkinson's disease, they are often overlooked. This
      article reviews the various skin disorders seen in Parkinson's disease and
      addresses the other dermatological questions that are frequently raised by those
      attending Parkinson's disease clinics. 

PMID- 25862734
TI  - Diagnosis of spinal xanthomatosis by next-generation sequencing: identifying a
      rare, treatable mimic of hereditary spastic paraparesis.
AB  - Cerebrotendinous xanthomatosis is an autosomal recessive disorder of bile acid
      metabolism causing a range of progressive neurological symptoms. Even in the
      presence of the classical triad of neurological dysfunction, tendon xanthoma and
      early onset cataracts, the diagnosis is often missed. It can mimic more common
      conditions such as hereditary spastic paraparesis or multiple sclerosis,
      particularly if the phenotype is spinal xanthomatosis where the disease causes a
      spastic paraplegia. Early recognition and treatment with chenodeoxycholic acid
      may prevent irreversible neurological damage. The introduction of next-generation
      sequencing to screen for a large number of genetic disorders associated with
      progressive spastic paraparesis will allow earlier identification and treatment
      of these patients and their families, and will particularly help in atypical
      cases such as the patient described here. 

PMID- 25862735
TI  - A Novel Mutation p.A59P in N-Terminal Domain of Methyl-CpG-Binding Protein 2
      Confers Phenotypic Variability in 3 Cases of Tunisian Rett Patients: Clinical
      Evaluations and In Silico Investigations.
AB  - Rett syndrome is a monogenic X-linked dominant neurodevelopmental disorder
      related to mutation in MECP2, which encodes the methyl-CpG-binding protein MeCP2.
      The aim of this study was to search for mutations of MECP2 gene in Tunisian Rett
      patients and to evaluate the impact of the found variants on structural and
      functional features of MeCP2. The result of mutation analysis revealed that 3
      Rett patients shared the same novel heterozygous point mutation c.175G>C
      (p.A59P). The p.A59P mutation was located in a conserved amino acid in the N
      terminal segment of MeCP2. This novel mutation confers a phenotypic variability
      with different clinical severity scores (3, 8, and 9) and predicted by Sift and
      PolyPhen to be damaging. Modeling results showed that p.A59P adds 2 hydrogen
      bonds and changes the structural conformation of MeCP2 with a significant root
      mean square deviation value (9.66 A), suggesting that this mutation could
      probably affect the conformation, function and stability of MeCP2. 

PMID- 25862736
TI  - Diagnoses in Pediatric Patients With Magnetic Resonance Imaging (MRI) Lesions
      Suspicious for Demyelination.
AB  - Magnetic resonance imaging (MRI) studies of the brain in pediatric patients
      frequently show abnormal white matter lesions, which may be concerning for
      demyelinating disease. This study aimed to determine the proportion of pediatric
      patients who have MRI lesions concerning for demyelinating disease at
      presentation and ultimately are diagnosed with a primary central nervous system
      demyelinating disease. A retrospective chart review was performed on MRI reports
      of patients who underwent imaging evaluation at a single tertiary pediatric
      hospital. Of 299 patients identified, 192 presented with acute neurologic
      complaints. In this group, >= 5 discrete lesions, African American race, and
      having brain stem, thalamic, cerebellar, or optic nerve lesions was associated
      with the patient being diagnosed with a disease that required further treatment.
      The other 107 patients underwent MRI for other indications. Among these subjects,
      having lesions within the corpus callosum or cerebellum was associated with being
      diagnosed with a disease requiring further treatment.

PMID- 25862737
TI  - A Preliminary Study of the Effects of an Arts Education Program on Executive
      Function, Behavior, and Brain Structure in a Sample of Nonclinical School-Aged
      Children.
AB  - The authors examined the effects of arts education on cognition, behavior, and
      brain of children. Twenty-nine nonclinical children participated in a 15-week
      arts education program that was composed of either creative movement or musical
      arts. Children completed the Wisconsin Card Sorting Test, clinical scales, and
      brain magnetic resonance imaging before and after the intervention. Following
      program completion, performances on the Wisconsin Card Sorting Test, the
      Children's Depression Inventory scores, and conduct disorder scores were
      significantly improved. Furthermore, cortical thickness in the left postcentral
      gyrus and superior parietal lobule were increased, and the mean diffusivity
      values in the right posterior corona radiate and superior longitudinal fasciculus
      were decreased. Positive correlations between changes in cognitive measurements
      and changes in cortical thickness were observed. This preliminary study suggests
      a positive effect of arts education on executive functions in association with
      brain changes. However, these findings must be interpreted with caution due to
      the noncomparative study design. 

PMID- 25862738
TI  - Posterior Reversible Encephalopathy Syndrome in Children With Hematologic
      Malignancies.
AB  - Since its original description 2 decades ago, posterior reversible encephalopathy
      syndrome has been reported in children with several predisposing conditions.
      Epidemiologic data of posterior reversible encephalopathy syndrome in children
      with hematologic malignancies is still scarce. Herein, we describe the clinical
      and radiologic features along with the outcome and follow-up of posterior
      reversible encephalopathy syndrome complicating the treatment of children with
      hematologic malignancies. Ten patients with a median age of 6.3 years were
      diagnosed with posterior reversible encephalopathy syndrome. Six of them were
      undergoing chemotherapy and the remaining 4 were at 37, 52, 78, and 857 days
      after allogenic hematopoietic stem cell transplant. The median follow-up was 27.6
      months. Even though follow-up imaging showed complete resolution of abnormalities
      in those 10 children, 2 developed secondary epilepsy. Despite accurate diagnosis
      of posterior reversible encephalopathy syndrome and immediate intervention,
      neurologic sequelae may still develop. Thus, a close follow-up should be
      considered in all patients. 

PMID- 25862739
TI  - The Clinical Utility of a Single-Nucleotide Polymorphism Microarray in Patients
      With Epilepsy at a Tertiary Medical Center.
AB  - Microarray testing has revolutionized clinical cytogenetics, as it provides a
      significantly higher resolution and greater clinical yield than karyotype
      analysis. This study assessed the clinical utility of single-nucleotide
      polymorphism microarray in patients with epilepsy. Study subjects were patients
      between the ages of birth to 23 years who were diagnosed with epilepsy and had a
      microarray performed at Cincinnati Children's Hospital Medical Center.
      Statistical analysis explored the association of microarray results and brain
      magnetic resonance imaging (MRI), seizure type, and structural malformations.
      Approximately 17.7% (26/147) of participants had an abnormal microarray as
      defined by laboratory guidelines. There were no differences in frequency of
      abnormal brain MRI or seizure type between the abnormal and normal microarray
      groups. There was a higher prevalence of musculoskeletal malformations (P <
      .0035) and cardiovascular malformations (P < .0081) in subjects with abnormal
      microarrays. Clinicians should consider microarray analysis in individuals who
      have epilepsy, especially in combination with musculoskeletal malformation or
      cardiovascular malformation. 

PMID- 25862740
TI  - Parental Stress in Families of Children With Autism and Other Developmental
      Disabilities.
AB  - The level of parental stress in families of children with autism and other
      developmental disabilities and its association with child comorbid symptoms was
      studied in an ethnically diverse population, in a cross-sectional study with
      structured interview. The sample included 50 families of children with autism and
      50 families of children with other developmental disabilities, matched by
      age/gender. Interview included Parenting Stress Index-Short Form,
      Gastrointestinal Questionnaire, Child Sleep Habits Questionnaire, and Aberrant
      Behavior Checklist. In this ethnically diverse sample, parental stress was
      significantly higher for the autism group and for non-Hispanic and US-born
      mothers. In both study groups, parental stress was related to child irritability.
      Parental stress was also related to gastrointestinal problems in the autism group
      and to sleep difficulties in the developmental disabilities group. Targeting
      child irritability may be particularly important in reducing parental stress for
      families of children with autism and other developmental disabilities. 

PMID- 25862744
TI  - Determination of Pinaverium Bromide in Human Plasma by a Sensitive and Robust
      UPLC-MS-MS Method and Application to a Pharmacokinetic Study in Mexican Subjects.
AB  - A high-throughput ultra-performance liquid chromatography coupled to tandem mass
      spectrometry (LC-ESI-MS-MS) method was developed for the determination of
      pinaverium bromide in human plasma. Protein precipitation with acetonitrile was
      used to extract pinaverium and itraconazole (as internal standard) from 500 uL
      plasma samples. The chromatographic separation was achieved with an Acquity UPLC
      BEH C18 column (1.7 um, 2.1 * 100 mm) using a mixture of acetonitrile-5 mM
      ammonium formate (80:20, v/v) as mobile phase. Isocratic elution at 0.3 mL/min
      was used. Detection was performed by positive ion electrospray tandem mass
      spectrometry on a XEVO TQ-S by multiple reaction monitoring mode. The mass
      transitions monitorized were as follows: m/z 511.2 -> 230 for pinaverium bromide,
      and m/z 705.29 -> 392.18 for the itraconazole. The method was validated over a
      concentration range of 12-12,000 pg/mL. The chromatographic method runtime is 2.5
      min and was applied to characterize the pharmacokinetics of pinaverium bromide
      after the oral administration of 100 mg to healthy Mexican subjects. 

PMID- 25862743
TI  - Gender differences in the trajectory of recovery in health status among young
      patients with acute myocardial infarction: results from the variation in
      recovery: role of gender on outcomes of young AMI patients (VIRGO) study.
AB  - BACKGROUND: Despite the excess risk of mortality in young women (<=55 years of
      age) after acute myocardial infarction (AMI), little is known about young women's
      health status (symptoms, functioning, quality of life) during the first year of
      recovery after an AMI. We examined gender differences in health status over time
      from baseline to 12 months after AMI. METHODS AND RESULTS: A total of 3501 AMI
      patients (67% women) 18 to 55 years of age were enrolled from 103 US and 24
      Spanish hospitals. Data were obtained by medical record abstraction and patient
      interviews at baseline hospitalization and 1 and 12 months after AMI. Health
      status was measured by generic (Short Form-12) and disease-specific (Seattle
      Angina Questionnaire) measures. We compared health status scores at all 3 time
      points and used longitudinal linear mixed-effects analyses to examine the
      independent effect of gender, adjusting for time and selected covariates. Women
      had significantly lower health status scores than men at each assessment (all P
      values <0.0001). After adjustment for time and all covariates, women had Short
      Form-12 physical/mental summary scores that were -0.96 (95% confidence interval
      [CI], -1.59 to -0.32) and -2.36 points (95% CI, -2.99 to -1.73) lower than those
      of men, as well as worse Seattle Angina Questionnaire physical limitations (-2.44
      points lower; 95% CI, -3.53 to -1.34), more angina (-1.03 points lower; 95% CI, 
      1.98 to -0.07), and poorer quality of life (-3.51 points lower; 95% CI, -4.80 to 
      2.22). CONCLUSION: Although both genders recover similarly after AMI, women have
      poorer scores than men on all health status measures, a difference that persisted
      throughout the entire year after discharge.

PMID- 25862742
TI  - Polygenic Overlap Between C-Reactive Protein, Plasma Lipids, and Alzheimer
      Disease.
AB  - BACKGROUND: Epidemiological findings suggest a relationship between Alzheimer
      disease (AD), inflammation, and dyslipidemia, although the nature of this
      relationship is not well understood. We investigated whether this phenotypic
      association arises from a shared genetic basis. METHODS AND RESULTS: Using
      summary statistics (P values and odds ratios) from genome-wide association
      studies of >200 000 individuals, we investigated overlap in single-nucleotide
      polymorphisms associated with clinically diagnosed AD and C-reactive protein
      (CRP), triglycerides, and high- and low-density lipoprotein levels. We found up
      to 50-fold enrichment of AD single-nucleotide polymorphisms for different levels
      of association with C-reactive protein, low-density lipoprotein, high-density
      lipoprotein, and triglyceride single-nucleotide polymorphisms using a false
      discovery rate threshold <0.05. By conditioning on polymorphisms associated with
      the 4 phenotypes, we identified 55 loci associated with increased AD risk. We
      then conducted a meta-analysis of these 55 variants across 4 independent AD
      cohorts (total: n=29 054 AD cases and 114 824 healthy controls) and discovered 2
      genome-wide significant variants on chromosome 4 (rs13113697; closest gene,
      HS3ST1; odds ratio=1.07; 95% confidence interval=1.05-1.11; P=2.86*10(-8)) and
      chromosome 10 (rs7920721; closest gene, ECHDC3; odds ratio=1.07; 95% confidence
      interval=1.04-1.11; P=3.38*10(-8)). We also found that gene expression of HS3ST1
      and ECHDC3 was altered in AD brains compared with control brains. CONCLUSIONS: We
      demonstrate genetic overlap between AD, C-reactive protein, and plasma lipids. By
      conditioning on the genetic association with the cardiovascular phenotypes, we
      identify novel AD susceptibility loci, including 2 genome-wide significant
      variants conferring increased risk for AD.

PMID- 25862745
TI  - A growth-rate composition formula for the growth of E.coli on co-utilized carbon
      substrates.
AB  - When bacteria are cultured in medium with multiple carbon substrates, they
      frequently consume these substrates simultaneously. Building on recent advances
      in the understanding of metabolic coordination exhibited by Escherichia coli
      cells through cAMP-Crp signaling, we show that this signaling system responds to
      the total carbon-uptake flux when substrates are co-utilized and derive a
      mathematical formula that accurately predicts the resulting growth rate, based
      only on the growth rates on individual substrates. 

PMID- 25862746
TI  - In reply.

PMID- 25862747
TI  - Semiconductor-based sequencing of formalin-fixed, paraffin-embedded colorectal
      cancer samples.

PMID- 25862748
TI  - Diagnostic value of plasma and urinary 2-hydroxyglutarate to identify patients
      with isocitrate dehydrogenase-mutated glioma.
AB  - BACKGROUND: Mutant isocitrate dehydrogenase (IDH) 1/2 enzymes can convert alpha
      ketoglutarate into 2-hydroxyglutarate (2HG). The aim of the present study was to
      explore whether 2HG in plasma and urine could predict the presence of IDH1/2
      mutations in patients with glioma. MATERIALS AND METHODS: All patients had
      histological confirmation of glioma and a recent brain magnetic resonance imaging
      scan showing the neoplastic lesion. Plasma and urine samples were taken from all
      patients, and the 2HG concentrations were determined using liquid chromatography
      tandem mass spectrometry. RESULTS: A total of 84 patients were enrolled: 38 with
      R132H-IDH1 mutated and 46 with wild type. Among the 38 patients with mutant IDH1,
      21 had high-grade glioma and 17 had low-grade glioma. Among the 46 patients with
      IDH1 wild-type glioma, 35 and 11 had high- and low-grade glioma, respectively. In
      all patients, we analyzed the mean 2HG concentration in the plasma, urine, and
      plasma/urine ratio (Ratio_2HG). We found a significant difference in the
      Ratio_2HG between patients with and without an IDH1 mutation (22.2 +/- 8.7 vs.
      15.6 +/- 6.8; p < .0001). The optimal cutoff value for Ratio_2HG to identify IDH1
      mutation was 19 (sensitivity, 63%; specificity, 76%; accuracy, 70%). In the
      patients with high-grade glioma only, the optimal cutoff value was 20
      (sensitivity, 76%; specificity, 89%; accuracy, 84%; positive predictive value,
      80%; negative predictive value, 86%). In 7 of 7 patients with high-grade glioma,
      we found a correlation between the Ratio_2HG value and the response to treatment.
      CONCLUSION: Ratio_2HG might be a predictor of the presence of IDH1 mutation. The
      measurement of 2HG could be useful for disease monitoring and also to assess the
      treatment effects in these patients.

PMID- 25862749
TI  - The 1964 Surgeon General's report and Americans' beliefs about smoking.
AB  - Half a century ago, on January 11, 1964, the U.S. Surgeon General's office
      released a landmark report on the health consequences of smoking. That report
      received massive media attention and triggered a steadily growing number of
      federal, state, and local restrictions on the advertising, sale, and use of
      cigarettes. Little is known about the report's impact on American public opinion
      because all the timely public opinion polls that measured the report's impact
      were privately commissioned by the tobacco industry and were not made publicly
      available. A review of these polls shows that the 1964 Surgeon General's report
      had a large and immediate effect on Americans' beliefs that cigarettes were a
      cause of lung cancer and of heart disease. However, the report had less impact on
      public preferences for government action or on smoking rates. 

PMID- 25862750
TI  - The origin of the medical research grant in the United States: the Rockefeller
      Foundation and the NIH Extramural Funding Program.
AB  - The establishment of National Institutes of Health (NIH) extramural grants in the
      second half of the twentieth century marked a signal shift in support for medical
      research in the United States and created an influential model for the rest of
      the world. A similar landmark development occurred in the first half of the
      twentieth century with the creation of the Rockefeller Foundation and its funding
      programs for medical research. The programs and support of the foundation had a
      dramatic impact on medical research in the United States and globally. This paper
      examines early connections between these two developments. The NIH grants have
      usually been seen as having their roots primarily in the government programs of
      the Second World War. This article finds direct and indirect influence by the
      Rockefeller Foundation, as well as parallel developments in these two monumental
      programs of support for medical research. 

PMID- 25862751
TI  - Jogging the institutional memory: writing the history of the federal government.

PMID- 25862755
TI  - Can staff and patient perspectives on hospital safety predict harm-free care? An
      analysis of staff and patient survey data and routinely collected outcomes.
AB  - BACKGROUND: Patients have the potential to provide feedback on the safety of
      their care. Recently, tools have been developed that ask patients to provide
      feedback on those factors that are known to contribute to safety, therefore
      providing information that can be used proactively to manage safety in hospitals.
      The aim of this study was to investigate whether the safety information provided
      by patients is different from that provided by staff and whether it is related to
      safety outcomes. METHOD: Data were collected from 33 hospital wards across 3
      acute hospital Trusts in the UK. Staff on these wards were asked to complete the
      four outcome measures of the Hospital Survey of Patient Safety Culture, while
      patients were asked to complete the Patient Measure of Safety and the friends and
      family test. We also collated publicly reported safety outcome data for 'harm
      free care' on each ward. This patient safety thermometer measure is used in the
      UK NHS to record the percentage of patients on a single day of each month on
      every ward who have received harm-free care (ie, no pressure ulcers, falls,
      urinary tract infections and hospital acquired new venous thromboembolisms).
      These data were used to address questions about the relationship between measures
      and the extent to which patient and staff perceptions of safety predict safety
      outcomes. RESULTS: The friends and family test, a single item measure of patient
      experience was associated with patients' perceptions of safety, but was not
      associated with safety outcomes. Staff responses to the patient safety culture
      survey were not significantly correlated with patient responses to the patient
      measure of safety, but both independently predicted safety outcomes. The
      regression models showed that staff perceptions (adjusted r(2)=0.39) and patient
      perceptions (adjusted r(2)=0.30) of safety independently predicted safety
      outcomes. When entered together both measures accounted for 49% of the variance
      in safety outcomes (adjusted r(2)=0.49), suggesting that there is overlap but
      some unique variance is also explained by these two measures. Based on responses
      to the Patient Measure of Safety it was also possible to identify differences
      between the acute Hospital Trusts. DISCUSSION: The findings suggest that although
      the views of patients and staff predict some overlapping variance in patient
      safety outcomes, both also offer a unique perspective on patient safety,
      contributing independently to the prediction of safety outcomes. These findings
      suggest that feedback from patients about the safety of the care that they
      receive can be used, in addition to data from staff to drive safety improvements
      in healthcare. TRIAL REGISTRATION NUMBER: ISRCTN07689702.

PMID- 25862756
TI  - Introducing consultant outpatient clinics to community settings to improve access
      to paediatrics: an observational impact study.
AB  - OBJECTIVES: In line with a national policy to move care 'closer to home', a
      specialist children's hospital in the National Health Service in England
      introduced consultant-led 'satellite' clinics to two community settings for
      general paediatric outpatient services. Objectives were to reduce non-attendance
      at appointments by providing care in more accessible locations and to create new
      physical clinic capacity. This study evaluated these satellite clinics to inform
      further development and identify lessons for stakeholders. METHODS: Impact of the
      satellite clinics was assessed by comparing community versus hospital-based
      clinics across the following measures: (1) non-attendance rates and associated
      factors (including patient characteristics and travel distance) using a logistic
      regression model; (2) percentage of appointments booked within local catchment
      area; (3) contribution to total clinic capacity; (4) time allocated to clinics
      and appointments; and (5) clinic efficiency, defined as the ratio of income to
      staff-related costs. RESULTS: Satellite clinics did not increase attendance
      beyond their contribution to shorter travel distance, which was associated with
      higher attendance. Children living in the most-deprived areas were 1.8 times more
      likely to miss appointments compared with those from least-deprived areas. The
      satellite clinics' contribution to activity in catchment areas and to total
      capacity was small. However, one of the two satellite clinics was efficient
      compared with most hospital-based clinics. CONCLUSIONS: Outpatient clinics were
      relocated in pragmatically chosen community settings using a 'drag and drop'
      service model. Such clinics have potential to improve access to specialist
      paediatric healthcare, but do not provide a panacea. Work is required to improve
      attendance as part of wider efforts to support vulnerable families. Satellite
      clinics highlight how improved management could contribute to better use of
      existing capacity.

PMID- 25862757
TI  - Preventing device-associated infections in US hospitals: national surveys from
      2005 to 2013.
AB  - BACKGROUND: Numerous initiatives have focused on reducing device-associated
      infections, contributing to an overall decrease in infections nationwide. To
      better understand factors associated with this decline, we assessed the use of
      key practices to prevent device-associated infections by US acute care hospitals
      from 2005 to 2013. METHODS: We mailed surveys to infection preventionists at a
      national random sample of ~600 US acute care hospitals in 2005, 2009 and 2013.
      Our survey asked about the use of practices to prevent the 3 most common device
      associated infections: central line-associated bloodstream infection (CLABSI),
      ventilator-associated pneumonia (VAP) and catheter-associated urinary tract
      infection (CAUTI). Using sample weights, we estimated the per cent of hospitals
      reporting regular use (a score of 4 or 5 on a scale from 1 (never use) to 5
      (always use)) of prevention practices from 2005 to 2013. RESULTS: The response
      rate was about 70% in all 3 periods. Use of most recommended prevention practices
      increased significantly over time. Among those showing the greatest increase were
      use of an antimicrobial dressing for preventing CLABSI (25-78%, p<0.001), use of
      an antimicrobial mouth rinse for preventing VAP (41-79%, p<0.001) and use of
      catheter removal prompts for preventing CAUTI (9-53%, p<0.001). Likewise, a
      significant increase in facility-wide surveillance was found for all three
      infections. Practices for which little change was observed included use of
      antimicrobial catheters to prevent either CLABSI or CAUTI. CONCLUSIONS: US
      hospitals have responded to the call to reduce infection by increasing use of key
      recommended practices. Vigilance is needed to ensure sustained improvement and
      additional strategies may still be required, given an apparent continuing lag in
      CAUTI prevention efforts.

PMID- 25862758
TI  - Chronic Exposure to Bisphenol A Reduces Successful Cardiac Remodeling After an
      Experimental Myocardial Infarction in Male C57bl/6n Mice.
AB  - Estrogenic compounds such as bisphenol A (BPA) leach from plastics into food and
      beverage containers. Increased BPA exposure has been correlated with increased
      cardiovascular disease. To test the hypothesis that increased BPA exposure
      reduces cardiovascular remodeling, we chronically exposed C57bl/6n male mice to
      BPA and performed a myocardial infarction (MI). We measured cardiac function, as
      well as myeloid and cardiac fibroblast accumulation and activity. We found
      increased early death as well as increased cardiac dilation and reduced cardiac
      function in surviving BPA-exposed mice. Matrix metalloproteinase-2 (MMP2) protein
      and activity were increased 1.5-fold in BPA-exposed heart. BPA-exposed mice had
      similar neutrophil infiltration; however, monocyte and macrophage (MPhi)
      infiltration into the ischemic area was 5-fold greater than VEH mice potentially
      due to a 2-fold increase in monocyte chemoattractant protein-1. Monocyte and MPhi
      exposure to BPA in vitro in primary bone marrow cultures or in isolated
      peritoneal MPhi increased polarization to an activated MPhi, increased MMP2 and
      MMP9 expression 2-fold and activity 3-fold, and increased uptake of microspheres
      3-fold. Cardiac fibroblasts (CF) differentiate to alpha-smooth muscle actin
      (alphaSMA) expressing myofibroblasts, migrate to the ischemic area and secrete
      collagen to strengthen the scar. Collagen and alphaSMA expression were reduced
      50% in BPA-exposed hearts. Chronic in vivo or continuous in vitro BPA exposure
      ablated transforming growth factor beta-mediated differentiation of CF, reduced
      alphaSMA expression 50% and reduced migration 40% yet increased secreted MMP2
      activity 2-fold. We conclude that chronic BPA exposure reduces the ability to
      successfully remodel after an MI by increasing MPhi-based inflammation and
      reducing myofibroblast repair function.

PMID- 25862759
TI  - Brain Penetration and Efficacy of Different Mebendazole Polymorphs in a Mouse
      Brain Tumor Model.
AB  - PURPOSE: Mebendazole (MBZ), first used as an antiparasitic drug, shows
      preclinical efficacy in models of glioblastoma and medulloblastoma. Three
      different mebendazole polymorphs (A, B, and C) exist, and a detailed assessment
      of the brain penetration, pharmacokinetics, and antitumor properties of each
      individual mebendazole polymorph is necessary to improve mebendazole-based brain
      cancer therapy. EXPERIMENTAL DESIGN AND RESULTS: In this study, various marketed
      and custom-formulated mebendazole tablets were analyzed for their polymorph
      content by IR spectroscopy and subsequently tested in an orthotopic GL261 mouse
      glioma model for efficacy and tolerability. The pharmacokinetics and brain
      concentration of mebendazole polymorphs and two main metabolites were analyzed by
      LC/MS. We found that polymorph B and C both increased survival in a GL261 glioma
      model, as B exhibited greater toxicity. Polymorph A showed no benefit. Polymorph
      B and C both reached concentrations in the brain that exceeded the IC50 in GL261
      cells 29-fold. In addition, polymorph C demonstrated an AUC0-24h brain-to-plasma
      (B/P) ratio of 0.82, whereas B showed higher plasma AUC and lower B/P ratio. In
      contrast, polymorph A presented markedly lower levels in the plasma and brain.
      Furthermore, the combination with elacridar was able to significantly improve the
      efficacy of polymorph C in GL261 glioma and D425 medulloblastoma models in mice.
      CONCLUSIONS: Among mebendazole polymorphs, C reaches therapeutically effective
      concentrations in the brain tissue and tumor with fewer side effects, and is the
      better choice for brain cancer therapy. Its efficacy can be further enhanced by
      combination with elacridar.

PMID- 25862760
TI  - An Antibody-Drug Conjugate Directed against Lymphocyte Antigen 6 Complex, Locus E
      (LY6E) Provides Robust Tumor Killing in a Wide Range of Solid Tumor Malignancies.
AB  - PURPOSE: Chemotherapies are limited by a narrow therapeutic index resulting in
      suboptimal exposure of the tumor to the drug and acquired tumor resistance. One
      approach to overcome this is through antibody-drug conjugates (ADC) that
      facilitate greater potency via target-specific delivery of highly potent
      cytotoxic agents. EXPERIMENTAL DESIGN: In this study, we used a bioinformatics
      approach to identify the lymphocyte antigen 6 complex locus E (LY6E), an IFN
      inducible glycosylphosphatidylinositol (GPI)-linked cell membrane protein as a
      promising ADC target. We developed a monoclonal anti-LY6E antibody and
      characterized in situ LY6E expression in over 750 cancer specimens and normal
      tissues. Target-dependent anti-LY6E ADC killing was investigated both in vitro
      and in vivo using patient-derived xenograft models. RESULTS: Using in silico
      approaches, we found that LY6E was significantly overexpressed and amplified in a
      wide array of different human solid tumors. IHC analysis revealed high LY6E
      protein expression in a number of tumor types, such as breast, lung, gastric,
      ovarian, pancreatic, kidney and head/neck carcinomas. Characterization of the
      endocytic pathways for LY6E revealed that the LY6E-specific antibody is
      internalized into cells leading to lysosomal accumulation. Consistent with this,
      a LY6E-specific ADC inhibited in vitro cell proliferation and produced durable
      tumor regression in vivo in clinically relevant LY6E-expressing xenograft models.
      CONCLUSIONS: Our results identify LY6E as a highly promising molecular ADC target
      for a variety of solid tumor types with current unmet medical need.

PMID- 25862761
TI  - Systematic Screening Identifies Dual PI3K and mTOR Inhibition as a Conserved
      Therapeutic Vulnerability in Osteosarcoma.
AB  - PURPOSE: Osteosarcoma is the most common cancer of bone occurring mostly in
      teenagers. Despite rapid advances in our knowledge of the genetics and cell
      biology of osteosarcoma, significant improvements in patient survival have not
      been observed. The identification of effective therapeutics has been largely
      empirically based. The identification of new therapies and therapeutic targets
      are urgently needed to enable improved outcomes for osteosarcoma patients.
      EXPERIMENTAL DESIGN: We have used genetically engineered murine models of human
      osteosarcoma in a systematic, genome-wide screen to identify new candidate
      therapeutic targets. We performed a genome-wide siRNA screen, with or without
      doxorubicin. In parallel, a screen of therapeutically relevant small molecules
      was conducted on primary murine- and primary human osteosarcoma-derived cell
      cultures. All results were validated across independent cell cultures and across
      human and mouse osteosarcoma. RESULTS: The results from the genetic and chemical
      screens significantly overlapped, with a profound enrichment of pathways
      regulated by PI3K and mTOR pathways. Drugs that concurrently target both PI3K and
      mTOR were effective at inducing apoptosis in primary osteosarcoma cell cultures
      in vitro in both human and mouse osteosarcoma, whereas specific PI3K or mTOR
      inhibitors were not effective. The results were confirmed with siRNA and small
      molecule approaches. Rationale combinations of specific PI3K and mTOR inhibitors
      could recapitulate the effect on osteosarcoma cell cultures. CONCLUSIONS: The
      approaches described here have identified dual inhibition of the PI3K-mTOR
      pathway as a sensitive, druggable target in osteosarcoma, and provide rationale
      for translational studies with these agents.

PMID- 25862762
TI  - Protein-bound uraemic toxins, dicarbonyl stress and advanced glycation end
      products in conventional and extended haemodialysis and haemodiafiltration.
AB  - BACKGROUND: Protein-bound uraemic toxins (PBUT), dicarbonyl stress and advanced
      glycation end products (AGEs) associate with cardiovascular disease in dialysis.
      Intensive haemodialysis (HD) may have significant clinical benefits. The aim of
      this study was to evaluate the acute effects of conventional and extended HD and
      haemodiafiltration (HDF) on reduction ratio (RR) and total solute removal (TSR)
      of PBUT, dicarbonyl stress compounds and AGEs. METHODS: Thirteen stable
      conventional HD patients randomly completed a single study of 4-h HD (HD4), 4-h
      HDF (HDF4), 8-h HD (HD8) and 8-h HDF (HDF8) with a 2-week interval between the
      study sessions. RR and TSR of PBUT [indoxyl sulphate (IS), p-cresyl sulphate
      (PCS), p-cresyl glucuronide, 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid
      (CMPF), indole-3-acetic acid (IAA) and hippuric acid] of free and protein-bound
      AGEs [N(epsilon)-(carboxymethyl)lysine (CML), N(epsilon)-(carboxyethyl)lysine
      (CEL), Ndelta-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine, pentosidine], as
      well as of dicarbonyl compounds [glyoxal, methylglyoxal, 3-deoxyglucosone], were
      determined. RESULTS: Compared with HD4, HDF4 resulted in increased RR of total
      and/or free fractions of IAA and IS as well as increased RR of free CML and CEL.
      HD8 and HDF8 showed a further increase in TSR and RR of PBUT (except CMPF), as
      well as of dicarbonyl stress and free AGEs compared with HD4 and HDF4. Compared
      with HD8, HDF8 only significantly increased RR of total and free IAA and free
      PCS, as well as RR of free CEL. CONCLUSIONS: Dialysis time extension (HD8 and
      HDF8) optimized TSR and RR of PBUT, dicarbonyl stress and AGEs, whereas HDF8 was
      superior to HD8 for only a few compounds.

PMID- 25862763
TI  - Emerging role of post-translational modifications in chronic kidney disease and
      cardiovascular disease.
AB  - Post-translational modifications (PTMs) of proteins and peptides have recently
      gained much attention, as they are involved in the pathogenesis of cardiovascular
      disease and eventually also play a role in the progression of chronic kidney
      disease (CKD). In this review, we provide an overview of post-translational
      protein modifications such as carbamylation, glycation and oxidation, starting
      with their definitions, mechanisms and clinical relevance in the setting of CKD
      and cardiovascular disease. The methods currently used for the identification
      and, in particular, quantification of PTMs are described and potential treatment
      options in the context of PTMs are reviewed. We foresee that advancements in mass
      spectrometry-based methods leading to the identification of novel disease markers
      and/or pathophysiologically relevant factors will certainly boost the clinical
      utility in sample analyses. 

PMID- 25862764
TI  - Nature and management of duplicate medication alerts.
AB  - OBJECTIVE: To investigate the nature of duplicate medication (DM) alerts, their
      management by community pharmacists, and potential characteristics of DM alerts
      that lead to interventions by pharmacists. METHODS: Observational study in 53
      community pharmacies. Each pharmacist registered the nature and management of 24
      DM alerts on a structured form. RESULTS: On average, the clinical decision
      support systems generated 20.4 DM alerts per 100 dispensed drugs. In half of the
      1272 registered alerts, the pharmacists judged that there was no risk for
      concurrent use of both prescriptions. In 32% of the alerts, the DM alert was
      generated for an intentional combination. In 17% of the alerts, there was a risk
      for unintentional concurrent use. In 32% of the alerts the pharmacists decided
      that one or more actions were needed: the electronic patient record was updated
      in 15% of the alerts and in 19% of the alerts the pharmacists performed an
      external action-for example, informing the patient or modifying the prescription
      (including 5 therapeutic prescription modifications and 22 logistic prescription
      modifications). Alerts concerning first dispensing were more likely to be
      followed by an external action than alerts concerning refills (40% vs 14%, P <
      .001). DISCUSSION AND CONCLUSION: In community pharmacy, prescription
      modifications based on DM alerts are rare, but DM alerts lead with some
      regularity to other actions-for example, patient instruction and update of the
      electronic patient record. As the current DM alerts are diverse and nonspecific
      in detecting situations where external action is considered relevant, other ways
      of alerting should therefore be considered.

PMID- 25862765
TI  - Subgraph augmented non-negative tensor factorization (SANTF) for modeling
      clinical narrative text.
AB  - OBJECTIVE: Extracting medical knowledge from electronic medical records requires
      automated approaches to combat scalability limitations and selection biases.
      However, existing machine learning approaches are often regarded by clinicians as
      black boxes. Moreover, training data for these automated approaches at often
      sparsely annotated at best. The authors target unsupervised learning for modeling
      clinical narrative text, aiming at improving both accuracy and interpretability.
      METHODS: The authors introduce a novel framework named subgraph augmented non
      negative tensor factorization (SANTF). In addition to relying on atomic features
      (e.g., words in clinical narrative text), SANTF automatically mines higher-order
      features (e.g., relations of lymphoid cells expressing antigens) from clinical
      narrative text by converting sentences into a graph representation and
      identifying important subgraphs. The authors compose a tensor using patients,
      higher-order features, and atomic features as its respective modes. We then apply
      non-negative tensor factorization to cluster patients, and simultaneously
      identify latent groups of higher-order features that link to patient clusters, as
      in clinical guidelines where a panel of immunophenotypic features and laboratory
      results are used to specify diagnostic criteria. RESULTS AND CONCLUSION: SANTF
      demonstrated over 10% improvement in averaged F-measure on patient clustering
      compared to widely used non-negative matrix factorization (NMF) and k-means
      clustering methods. Multiple baselines were established by modeling patient data
      using patient-by-features matrices with different feature configurations and then
      performing NMF or k-means to cluster patients. Feature analysis identified latent
      groups of higher-order features that lead to medical insights. We also found that
      the latent groups of atomic features help to better correlate the latent groups
      of higher-order features.

PMID- 25862766
TI  - The relationship between corticosteroids and symptoms in patients with primary
      brain tumors: utility of the Dexamethasone Symptom Questionnaire-Chronic.
AB  - BACKGROUND: Corticosteroids can have many side effects that impact the patient's
      quality of life and functional status. The Dexamethasone Symptom Questionnaire
      Chronic (DSQ-C) was developed to report corticosteroid side effects. This study's
      objective was to evaluate the utility of the DSQ-C and report associated signs
      and symptoms in brain tumor patients. METHODS: Data collection included
      demographic and disease characteristics and the DSQ-C. Descriptive statistics
      were used to report associations among variables. Linear regression models were
      applied to assess the effects of the cumulative daily dose (mg/d * total d) on
      DSQ-C scores. Psychometrics included factor analysis to assess construct validity
      and Cronbach's alpha for internal consistency. RESULTS: Ninety-six adult patients
      with primary (77%) or metastatic (23%) brain tumors participated, with 74% on
      corticosteroids. Participants were primarily white (83%) males (65%) between 20
      and 75 years of age (median, 53). Median corticosteroid dose duration was 4
      mg/day for 1 month (range, 0-26 mo). The DSQ-C scores ranged from 17 to 54 (mean
      of 27), with 35% reporting increased appetite and trouble sleeping. Factor
      analysis indicated 6 underlying constructs explaining 53% of variance. DSQ-C
      internal consistency (reliability) was 0.77. The DSQ-C discriminated between
      patients who were on steroids and those who were not (P < .01), and cumulative
      dose predicted DSQ-C scores (P < .001). CONCLUSIONS: This study demonstrated the
      potential use of the DSQ-C as a screening tool for side effects associated with
      corticosteroid use in brain tumor patients. Future analyses should include
      longitudinal evaluation of severity and biologic underpinnings of variability of
      timing and severity of symptoms.

PMID- 25862767
TI  - Three-dimensional printing of anatomically accurate, patient specific
      intracranial aneurysm models.
AB  - OBJECTIVE: To develop and validate a method for creating realistic, patient
      specific replicas of cerebral aneurysms by means of fused deposition modeling.
      METHODS: The luminal boundaries of 10 cerebral aneurysms, together with adjacent
      proximal and distal sections of the parent artery, were segmented based on DSA
      images, and corresponding virtual three-dimensional (3D) surface reconstructions
      were created. From these, polylactic acid and MakerBot Flexible Filament replicas
      of each aneurysm were created by means of fused deposition modeling. The accuracy
      of the replicas was assessed by quantifying statistical significance in the
      variations of their inner dimensions relative to 3D DSA images. Feasibility for
      using these replicas as flow phantoms in combination with phase contrast MRI was
      demonstrated. RESULTS: 3D printed aneurysm models were created for all 10
      subjects. Good agreement was seen between the models and the source anatomy.
      Aneurysm diameter measurements of the printed models and source images correlated
      well (r=0.999; p<0.001), with no statistically significant group difference
      (p=0.4) or observed bias. The SDs of the measurements were 0.5 mm and 0.2 mm for
      source images and 3D models, respectively. 3D printed models could be imaged with
      flow via MRI. CONCLUSIONS: The 3D printed aneurysm models presented were accurate
      and were able to be produced inhouse. These models can be used for previously
      cited applications, but their anatomical accuracy also enables their use as MRI
      flow phantoms for comparison with ongoing studies of computational fluid
      dynamics. Proof of principle imaging experiments confirm MRI flow phantom
      utility.

PMID- 25862769
TI  - Pelvic floor muscle training for urinary incontinence in female stroke patients:
      a randomized, controlled and blinded trial.
AB  - OBJECTIVE: To examine the effects of pelvic floor muscle training (PFMT) on the
      contractility of pelvic floor muscle and lower urinary tract symptoms in female
      stroke patients. DESIGN: Randomized, single-blind controlled study. SETTING:
      Outpatient rehabilitation hospital. SUBJECTS: Thirty one female patients who were
      more than three months post-stroke and stress urinary incontinence.
      INTERVENTIONS: The subjects were randomized to either a PFMT group (n = 16), or a
      control group (n = 15). Both groups received general rehabilitation exercise for
      6 weeks, but the PFMT group additionally received PFMT for 6 weeks. MAIN
      MEASURES: Vaginal function test using a perineometer (maximal vaginal squeeze
      pressure) and intra-vaginal electromyography (activity of pelvic floor muscle),
      and urinary symptoms and quality of life using a Bristol Female Lower Urinary
      Tract Symptom questionnaire. RESULTS: After intervention, the maximal vaginal
      squeeze pressures for the PFMT and control groups were 18.35 (5.24) and 8.46
      (3.50) mmHg, respectively. And the activities of pelvic floor muscle of the PFMT
      and control groups was 12.09 (2.24) ? and 9.33 (3.40) ?, respectively. After
      intervention, the changes of scores for inconvenience in the activity of daily
      living of the PFMT and control groups were -15.00 (6.25) and -0.17 (1.59),
      respectively. In addition, the changes of score for lower urinary tract symptom
      was improved more in the PFMT group (-4.17 (4.00)) than in the control group (
      0.25 (1.29)) (P < 0.05). CONCLUSIONS: These findings suggest that PFMT is
      beneficial for the management of urinary incontinence in female stroke patients.

PMID- 25862770
TI  - Comparative effectiveness of ultrasonophoresis and iontophoresis in impingement
      syndrome: a double-blind, randomized, placebo controlled trial.
AB  - OBJECTIVE: To estimate the effectiveness of ultrasonophoresis and iontophoresis
      with sodium diclofenac used in addition to an exercise program for patients with
      impingement syndrome. DESIGN: Multicentre, double-blind, placebo randomized
      controlled trial. SETTING: "Mancha Centro" Outpatient primary care clinic
      (Spain). PARTICIPANTS: A total of 175 patients were considered, of whom 88 met
      criteria and agreed. INTERVENTION: The patients were randomly assigned to one of
      three groups: a) standard treatment (supervised exercises and cryotherapy) along
      with placebo iontophoresis and placebo ultrasonophoresis; b) standard treatment,
      iontophoresis, and placebo ultrasonophoresis; and c) standard treatment,
      ultrasonophoresis, and placebo iontophoresis. All patients received 15 treatment
      sessions. OUTCOME MEASURES: Baseline, 6-, and 12-week evaluations were carried
      out. Functionality, pain, range of motion, strength and quality of life were
      assessed with the Disabilities of the Arm, Shoulder and Hand Questionnaire
      (DASH), Constant-Murley score, and SF-36 scale. RESULTS: Ultrasonophoresis group
      experienced significant decreases in pain compared to the standard treatment
      group (12.7 and 13.5 points in "bodily pain" dimension of SF-36; and 1,5 and 2,2
      points in "pain" dimension of Constant Murley after 6 and 12 weeks of therapy,
      respectively). They also reported improved range of motion compared to the
      exercises group (2,1 points in Constant-Murley after 6 weeks and 12 weeks),
      better vitality and overall health (SF-36 dimensions). Iontophoresis, however,
      led to no significant improvements when added to the standard treatment.
      CONCLUSION: In patients with impingement syndrome, a combination of
      ultrasonophoresis and an exercise program are better than a combination of
      iontophoresis and the same exercise program or the exercise program alone.

PMID- 25862771
TI  - Mount Fuji sign following surgical drainage of spinal epidural abscess.

PMID- 25862772
TI  - The use of adjunctive traditional Chinese medicine therapy and survival outcome
      in patients with head and neck cancer: a nationwide population-based cohort
      study.
AB  - BACKGROUND: Traditional Chinese medicine (TCM) is widely used in the treatment of
      patients with several types of cancer. However, no large-scale clinical studies
      have evaluated whether TCM is associated with better survival in patients with
      head and neck cancer (HNC). METHODS: The Taiwan National Health Insurance
      Research Database was used to conduct a retrospective cohort study of patients
      with HNC between 2001 and 2011. The patients with HNC were separated into TCM
      users and non-users, and Cox regression models were applied to determine the
      association between the use of TCM and survival outcome. RESULTS: The TCM and
      comparison cohorts comprised data for 2966 and 2670 patients, respectively. The
      mean age was 51.3 years in the TCM cohort and 51.7 years in the comparison
      cohort. Multivariate analysis demonstrated that the use of TCM was significantly
      associated with lower risk of all-cause mortality by 32% (adjusted hazard ratio,
      0.68; 95% confidence interval, 0.62-0.75). Patients with longer TCM use had a
      lower mortality rate (P for trend < 0.001). CONCLUSIONS: Our study showed that
      adjunctive therapy with TCM is associated with higher survival outcome. However,
      some limitations exist, such as the lack of information of cancer stage. In
      addition, causality cannot be assessed with this retrospective study. A
      randomized controlled trial to test the effect of adjunctive TCM therapy in HNC
      patients is needed.

PMID- 25862773
TI  - Leptospirosis and Jarisch-Herxheimer reaction.

PMID- 25862774
TI  - Septic arthritis and smoldering myeloma.

PMID- 25862775
TI  - American society of Nephrology Quiz and Questionnaire 2014: transplantation.
AB  - The Nephrology Quiz and Questionnaire remains an extremely popular session for
      attendees of the Annual Kidney Week Meeting of the American Society of
      Nephrology. Once again, the conference hall was overflowing with audience members
      and eager quiz participants. Topics covered by the expert discussants included
      electrolyte and acid-base disorders, glomerular disease, ESRD/dialysis, and
      transplantation. Complex cases representing each of these categories along with
      single best answer questions were prepared and submitted by the panel of experts.
      Before the meeting, program directors of United States nephrology training
      programs and nephrology fellows answered the questions through an internet-based
      questionnaire. During the live session, members of the audience tested their
      knowledge and judgment on a series of case-oriented questions prepared and
      discussed by experts. They compared their answers in real time using audience
      response devices with the answers of the nephrology fellows and training program
      directors. The correct and incorrect answers were then discussed after the
      audience responses and the results of the questionnaire were displayed. As
      always, the audience, lecturers, and moderators enjoyed this educational session.
      This article recapitulates the session and reproduces its educational value for
      the readers of CJASN. Enjoy the clinical cases and expert discussions. 

PMID- 25862776
TI  - Drug-induced glomerular disease: direct cellular injury.
AB  - The potential of medications to cause kidney injury is well known. Although
      nephrotoxicity is most commonly associated with injury in the tubulointerstitial
      compartment as either acute tubular necrosis or acute interstitial nephritis, a
      growing body of literature has also highlighted the potential for drug-induced
      glomerular lesions. This review surveys the three primary patterns of drug
      induced glomerular diseases stratified by the cell type at which the glomerular
      lesion is focused: visceral epithelial cell (or podoctye) injury, endothelial
      cell injury, and mesangial cell injury. A number of commonly prescribed
      medications, including IFNs, bisphosphonates, nonsteroidal anti-inflammatory
      drugs, antiplatelet agents, and antiangiogenesis drugs, that are both prescribed
      and available over the counter, have been implicated in these iatrogenic forms of
      glomerular disease. Recognition of these drug-induced etiologies of glomerular
      disease and rapid discontinuation of the offending agent are critical to
      maximizing the likelihood of renal function recovery. 

PMID- 25862777
TI  - Associations between Intensity of RRT, Inflammatory Mediators, and Outcomes.
AB  - BACKGROUND AND OBJECTIVES: Critically ill patients requiring RRT have higher
      circulating plasma concentrations of inflammatory and apoptosis markers that are
      associated with subsequent RRT dependence and death. Whether intensive dosing of
      RRT is associated with changes in specific mediators is unknown. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: A multicenter, prospective, cohort study of 817
      critically ill patients receiving RRT ancillary to the Veterans Affairs/National
      Institutes of Health Acute Renal Failure Trial Network study was conducted
      between November 2003 and July 2007. Plasma inflammatory (IL-6, IL-8, IL-10, IL
      18, and macrophage migration inhibitory factor) and apoptosis (TNF receptor-I
      [TNFR-I], TNFR-II, and death receptor-5) biomarkers on days 1 and 8 were examined
      after initiation of intensive RRT. Whether intensive RRT, given day 1 biomarkers,
      is associated with RRT independence and lower mortality at day 60 was also
      examined. RESULTS: Overall, no differences were found in day 8 biomarker
      concentrations between intensive and less-intensive RRT groups. When adjusted for
      day 1 biomarkers and clinical variables, intensive RRT was not associated with
      renal recovery (adjusted odds ratio [OR], 0.80; 95% confidence interval, 0.56 to
      1.14) or mortality (adjusted OR, 1.15; 95% confidence interval, 0.81 to 1.64).
      Use of intensive RRT, however, was associated with lower day 8 concentrations
      when day 1 plasma IL-6, macrophage migration inhibitory factor, and TNFR-I
      concentrations were high (interaction P value for all markers, <0.01). In
      contrast, day 8 marker concentrations were higher when day 1 levels were low
      (P<0.01). Elevated biomarker concentrations on day 8 among 476 participants were
      associated with lower renal recovery (adjusted OR range, 0.19-0.87) and higher
      mortality (adjusted OR range, 1.26-3.18). CONCLUSIONS: Among critically ill
      patients receiving RRT, intensive dosing of RRT has variable association with
      biomarker concentration and no association with renal recovery and mortality.
      However, elevated concentrations of inflammatory and apoptosis markers on day 8
      of RRT were associated with RRT dependence and death.

PMID- 25862778
TI  - Obstructive Sleep Apnea Severity and Overnight Body Fluid Shift before and after
      Hemodialysis.
AB  - BACKGROUND AND OBJECTIVES: Obstructive sleep apnea is associated with
      significantly increased cardiovascular morbidity and mortality. Fluid overload
      may promote obstructive sleep apnea in patients with ESRD through an overnight
      fluid shift from the legs to the neck soft tissues. Body fluid shift and severity
      of obstructive sleep apnea before and after hemodialysis were compared in
      patients with ESRD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Seventeen
      patients with hemodialysis and moderate to severe obstructive sleep apnea were
      included. Polysomnographies were performed the night before and after
      hemodialysis to assess obstructive sleep apnea, and bioimpedance was used to
      measure fluid overload and leg fluid volume. RESULTS: The mean overnight rostral
      fluid shift was 1.27+/-0.41 L prehemodialysis; it correlated positively with
      fluid overload volume (r=0.39; P=0.02) and was significantly lower
      posthemodialysis (0.78+/-0.38 L; P<0.001). There was no significant difference in
      the mean obstructive apnea-hypopnea index before and after hemodialysis (46.8+/
      22.0 versus 42.1+/-18.6 per hour; P=0.21), but obstructive apnea-hypopnea index
      was significantly lower posthemodialysis (-10.1+/-10.8 per hour) in the group of
      12 patients, with a concomitant reduction of fluid overload compared with
      participants without change in fluid overload (obstructive apnea-hypopnea index
      +8.2+/-16.1 per hour; P<0.01). A lower fluid overload after hemodialysis was
      significantly correlated (r=0.49; P=0.04) with a lower obstructive apnea-hypopnea
      index. Fluid overload-assessed by bioimpedance-was the best predictor of the
      change in obstructive apnea-hypopnea index observed after hemodialysis
      (standardized r=-0.68; P=0.01) in multivariate regression analysis. CONCLUSIONS:
      Fluid overload influences overnight rostral fluid shift and obstructive sleep
      apnea severity in patients with ESRD undergoing intermittent hemodialysis.
      Although no benefit of hemodialysis on obstructive sleep apnea severity was
      observed in the whole group, the change in obstructive apnea-hypopnea index was
      significantly correlated with the change in fluid overload after hemodialysis.
      Moreover, the subgroup with lower fluid overload posthemodialysis showed a
      significantly lower obstructive sleep apnea severity, which provides a strong
      incentive to further study whether optimizing fluid status in patients with
      obstructive sleep apnea and ESRD will improve the obstructive apnea-hypopnea
      index.

PMID- 25862779
TI  - Associations of Posthemodialysis Weights above and below Target Weight with All
      Cause and Cardiovascular Mortality.
AB  - BACKGROUND AND OBJECTIVES: Fluid removal via ultrafiltration is a primary
      function of hemodialysis, and inadequate volume control is associated with
      significant morbidity and mortality among chronic dialysis patients. Treatment-to
      treatment fluid removal goals are typically calculated on the basis of
      interdialytic weight gain and prescribed target weight. The clinical effect of
      frequent missed target weights is unclear. This study was designed to evaluate
      the associations of postdialysis weights above and below the prescribed target
      weight (separately) and outcomes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:
      Data were taken from a national cohort of 10,785 prevalent, thrice-weekly, in
      center hemodialysis patients dialyzing from 2005 to 2008 (median time at risk,
      2.1 [25th percentile, 75th percentile] years) at a single dialysis organization.
      Patients were characterized as having an above target weight miss if their
      postdialysis weight was >2 kg above target weight in at least 30% of baseline
      treatments (14.6% of cohort), or they were characterized as control otherwise.
      Below target weight miss characterization was analogous for patients with
      postdialysis weight >2 kg below target weight (6.6% of cohort). Coprimary
      endpoints were all-cause and cardiovascular mortality. RESULTS: Above target
      weight miss in at least 30% of treatments (versus not) was associated with
      greater all-cause mortality (adjusted hazard ratio, 1.28; 95% confidence
      interval, 1.15 to 1.43); and below target weight miss in at least 30% of
      treatments (versus not) was associated with greater all-cause mortality (adjusted
      hazard ratio, 1.22; 95% confidence interval, 1.05 to 1.40). Both above and below
      target weight misses were also significantly associated with greater
      cardiovascular mortality. Secondary analyses demonstrated dose-response
      relationships between target weight misses and mortality. Results from
      sensitivity analyses considering the difference in postdialysis and target
      weights as a proportion of body weight were analogous to the primary results.
      CONCLUSIONS: Postdialysis weights >2 kg above and below target weight are
      associated with higher all-cause and cardiovascular mortality. Consistent target
      weight achievement is a viable target for improving fluid management.

PMID- 25862780
TI  - Posthemodialysis weights and mortality: another narrow range target?

PMID- 25862781
TI  - A partly thrombosed, non-coronary sinus of Valsalva aneurysm.

PMID- 25862783
TI  - Erratum for La Rosa et al., In vivo assessment of growth and virulence gene
      expression during commensal and pathogenic lifestyles of luxABCDE-tagged
      Enterococcus faecalis strains in murine gastrointestinal and intravenous
      infection models.

PMID- 25862784
TI  - Erratum for Wang et al., Arsenite oxidase also functions as an antimonite
      oxidase.

PMID- 25862786
TI  - Impact of estrogen and progesterone receptor expression on the clinical and
      molecular features of papillary thyroid cancer.
AB  - BACKGROUND: Thyroid cancer is highly prevalent in women during the fertile age,
      which suggests a possible impact of hormonal and reproductive factors. METHODS:
      We studied the expression of estrogen receptor alpha (ERalpha or ESR1) and
      progesterone receptor (PR or PGR) in 182 female and male patients with papillary
      thyroid cancer and correlated it to clinical and molecular features. RESULTS:
      ERalpha and PR expression was found in 66.5 and 75.8% of patients respectively
      and was significantly correlated with larger tumor size and with a non-incidental
      diagnosis. Moreover, a trend toward a higher prevalence of local metastases was
      observed in ER- and PR-expressing tumors, which possibly indicates a more
      aggressive behavior. Interestingly, the occurrence of the 'receptor conversion'
      phenomenon, which has already been reported to have a negative prognostic effect
      in breast cancer, was demonstrated for the first time in thyroid tumors. Indeed,
      almost all of the ERalpha-positive primary tumors analyzed had ERalpha-negative
      metastatic lymph nodes. At the genetic analyses, BRAF(V600E) mutation was
      detected in 23.2% of the tumors and had a higher prevalence in larger tumors and
      in those with a stronger ERalpha or PR staining. CONCLUSIONS: The whole of the
      findings reported in the present study argue for an association between ERalpha
      and PR sex hormone receptor expression and a more aggressive presentation.
      Although no impact on outcome was found, the evaluation of ERalpha and PR
      receptor expression could add insights into the biological behavior of tumors and
      could modify the follow-up, particularly in fertile women affected with
      persistent disease.

PMID- 25862788
TI  - Falls research: stumbling or striding?

PMID- 25862787
TI  - ENDOCRINOLOGY IN PREGNANCY: Influence of maternal vitamin D status on obstetric
      outcomes and the fetal skeleton.
AB  - Vitamin D status has been increasingly associated with wide-ranging clinical
      outcomes. There is now a wealth of observational studies reporting on its
      associations with obstetric complications, including pre-eclampsia, gestational
      diabetes and the mode and timing of delivery. The findings are inconsistent, and
      currently there is a lack of data from high-quality intervention studies to
      confirm a causal role for vitamin D in these outcomes. This is similarly true
      with regards to fetal development, including measures of fetal size and skeletal
      mineralisation. Overall, there is an indication of possible benefits of vitamin D
      supplementation during pregnancy for offspring birthweight, calcium
      concentrations and bone mass as well as for reduced maternal pre-eclampsia.
      However, for none of these outcomes is the current evidence base conclusive, and
      the available data justify the instatement of high-quality randomised placebo
      controlled trials in a range of populations and health care settings to establish
      the potential efficacy and safety of vitamin D supplementation to improve
      particular outcomes. 

PMID- 25862789
TI  - Ubiquitin-like protein UBL5 promotes the functional integrity of the Fanconi
      anemia pathway.
AB  - Ubiquitin and ubiquitin-like proteins (UBLs) function in a wide array of cellular
      processes. UBL5 is an atypical UBL that does not form covalent conjugates with
      cellular proteins and which has a known role in modulating pre-mRNA splicing.
      Here, we report an unexpected involvement of human UBL5 in promoting the function
      of the Fanconi anemia (FA) pathway for repair of DNA interstrand crosslinks
      (ICLs), mediated by a specific interaction with the central FA pathway component
      FANCI. UBL5-deficient cells display spliceosome-independent reduction of FANCI
      protein stability, defective FANCI function in response to DNA damage and
      hypersensitivity to ICLs. By mapping the sequence determinants underlying UBL5
      FANCI binding, we generated separation-of-function mutants to demonstrate that
      key aspects of FA pathway function, including FANCI-FANCD2 heterodimerization,
      FANCD2 and FANCI monoubiquitylation and maintenance of chromosome stability after
      ICLs, are compromised when the UBL5-FANCI interaction is selectively inhibited by
      mutations in either protein. Together, our findings establish UBL5 as a factor
      that promotes the functionality of the FA DNA repair pathway. 

PMID- 25862790
TI  - A grab to move on: ER-endosome contacts in membrane protrusion formation and
      neurite outgrowth.

PMID- 25862791
TI  - Effectiveness and safety of dabigatran and warfarin in real-world US patients
      with non-valvular atrial fibrillation: a retrospective cohort study.
AB  - BACKGROUND: The recent availability of dabigatran, a novel oral anticoagulant,
      provided a new treatment option for stroke prevention in atrial fibrillation
      beyond warfarin, the main therapy for years. Little is known about their real
      world comparative effectiveness and safety, even less among patient demographic
      and clinical subgroups. METHODS AND RESULTS: Using a cohort of non-valvular AF
      patients initiating anticoagulation from October 2010 to December 2012 drawn from
      a large US database of commercial and Medicare supplement claims, we applied
      propensity score weights to Cox proportional hazards regression to assess the
      comparative effectiveness and safety of dabigatran versus warfarin. Analyses were
      repeated among clinical and demographic subgroups using stratum-specific
      propensity scores as an exploratory analysis. Of the 64 935 patients initiating
      anticoagulation, 32.5% used dabigatran. Compared with warfarin, dabigatran was
      associated with a lower risk of ischemic stroke or systemic embolism (composite
      adjusted Hazard Ratio [aHR], 95% CI: 0.86, 95% CI: 0.79 to 0.93), hemorrhagic
      stroke (aHR: 0.51, 0.40 to 0.65), and acute myocardial infarction (aHR: 0.88, 95%
      CI: 0.77 to 0.99), and no relation was seen between dabigatran and the composite
      harm outcome (aHR: 0.94, 95% CI: 0.87 to 1.01). However, dabigatran was
      associated with a higher risk of gastrointestinal bleeding (aHR: 1.11, 95% CI:
      1.02 to 1.22). Estimates of effectiveness and safety appeared to be mostly
      similar across subgroups. CONCLUSIONS: Dabigatran could be a safe and potentially
      more effective alternative to warfarin in patients with atrial fibrillation
      managed in routine practice settings.

PMID- 25862793
TI  - Do children recover better from arterial ischemic stroke than young adults?

PMID- 25862792
TI  - Blood pressure, sex, and female sex hormones influence renal inner medullary
      nitric oxide synthase activity and expression in spontaneously hypertensive rats.
AB  - BACKGROUND: We previously reported that sexually mature female spontaneously
      hypertensive rats (SHRs) have greater nitric oxide (NO) synthase (NOS) enzymatic
      activity in the renal inner medulla (IM), compared to age-matched males. However,
      the mechanisms responsible for this sexual dimorphism are unknown. The current
      study tested the hypothesis that sex differences in renal IM NOS activity and
      NOS1 expression in adult SHRs develop with sexual maturation and increases in
      blood pressure (BP) in a female sex hormone-dependent manner. METHODS AND
      RESULTS: Renal IM were isolated from sexually immature 5-week-old and sexually
      mature 13-week-old male and female SHRs. Whereas NOS activity and NOS1 expression
      were comparable in 5- and 13-week-old male SHRs and 5-week-old female SHRs, 13
      week-old females had greater NOS activity and NOS1 expression, compared to 5-week
      old female SHRs and age-matched males. NOS3 expression was greater in 5-week-old
      than 13-week-old SHRs regardless of sex. Treatment with antihypertensive therapy
      (hydrochlorothiazide and reserpine) from 6 to 12 weeks of age to attenuate age
      related increases in BP abolished the sex difference in NOS activity and NOS1
      expression between sexually mature SHR males and females. To assess the role of
      female sex hormones in age-related increases in NOS, additional females were
      ovariectomized (OVX), and NOS activity was studied 8 weeks post-OVX. OVX
      decreased NOS activity and NOS1 expression. CONCLUSIONS: The sex difference in
      renal IM NOS in SHR is mediated by a sex hormone- and BP-dependent increase in
      NOS1 expression and NOS activity exclusively in females.

PMID- 25862794
TI  - CT within 6 hours of headache onset to rule out subarachnoid hemorrhage in
      nonacademic hospitals.
AB  - OBJECTIVE: To investigate whether staff radiologists working in nonacademic
      hospitals can adequately rule out subarachnoid hemorrhage (SAH) on head CT <6
      hours after headache onset. METHODS: In a multicenter, retrospective study, we
      studied a consecutive series of patients presenting with acute headache to 11
      nonacademic hospitals. Inclusion criteria were (1) normal level of consciousness
      without focal deficits, (2) head CT <6 hours after headache onset and reported
      negative for the presence of SAH by a staff radiologist, and (3) subsequent CSF
      spectrophotometry. Two neuroradiologists and one stroke neurologist from 2
      academic tertiary care centers independently reviewed admission CTs of patients
      with CSF results that were considered positive for presence of bilirubin
      according to local criteria. We investigated the negative predictive value for
      detection of SAH by staff radiologists in nonacademic hospitals on head CT in
      patients scanned <6 hours after onset of acute headache. RESULTS: Of 760 included
      patients, CSF analysis was considered positive for bilirubin in 52 patients (7%).
      Independent review of these patients' CTs identified one patient (1/52; 2%) with
      a perimesencephalic nonaneurysmal SAH. Negative predictive value for detection of
      subarachnoid blood by staff radiologists working in a nonacademic hospital was
      99.9% (95% confidence interval 99.3%-100.0%). CONCLUSIONS: Our results support a
      change of practice wherein a lumbar puncture can be withheld in patients with a
      head CT scan performed <6 hours after headache onset and reported negative for
      the presence of SAH by a staff radiologist in the described nonacademic setting.

PMID- 25862796
TI  - VEGF isoforms as outcome biomarker for anti-angiogenic therapy in recurrent
      glioblastoma.

PMID- 25862795
TI  - Clinical and genetic spectrum in limb-girdle muscular dystrophy type 2E.
AB  - OBJECTIVE: To determine the clinical spectrum of limb-girdle muscular dystrophy
      2E (LGMD2E) and to investigate whether genetic or biochemical features can
      predict the phenotype of the disease. METHODS: All LGMD2E patients followed in
      participating centers were included. A specific clinical protocol was created,
      including quantitative evaluation of motor, respiratory, and cardiac function.
      Phenotype was defined as severe or mild if the age at loss of ambulation occurred
      before or after 18 years. Molecular analysis of SGCB gene and biochemical
      features of muscle biopsies were reviewed. RESULTS: Thirty-two patients were
      included (16 male, 16 female; age 7-67 years; 15 severe, 12 mild, and 5 unknown).
      Neurologic examination showed proximal muscle weakness in all patients, but
      distal involvement was also observed in patients with severe disease early in the
      disease course. Cardiac involvement was observed in 20 patients (63%) even before
      overt muscle involvement. Six patients had restrictive respiratory insufficiency
      requiring assisted ventilation (19%). Seventeen different mutations were
      identified, and 3 were recurrent. The c.377_384dup (13 alleles) was associated
      with the severe form, the c.-22_10dup (10) with the milder form, and the c.341C>T
      (9) with both. The entire sarcoglycan complex was undetectable by muscle
      immunohistochemistry or Western blot in 9/10 severe cases and reduced in 7/7 mild
      cases. The residual amount of sarcoglycan in muscle resulted a predictor of age
      at loss of ambulation. CONCLUSIONS: This study expands the spectrum of phenotype
      in beta-sarcoglycanopathy and provides strong evidence that severity of clinical
      involvement may be predicted by SGCB gene mutation and sarcoglycan protein
      expression.

PMID- 25862797
TI  - Long-term outcome after arterial ischemic stroke in children and young adults.
AB  - OBJECTIVE: To compare long-term outcome of children and young adults with
      arterial ischemic stroke (AIS) from 2 large registries. METHODS: Prospective
      cohort study comparing functional and psychosocial long-term outcome (>=2 years
      after AIS) in patients who had AIS during childhood (1 month-16 years) or young
      adulthood (16.1-45 years) between January 2000 and December 2008, who consented
      to follow-up. Data of children were collected prospectively in the Swiss
      Neuropediatric Stroke Registry, young adults in the Bernese stroke database.
      RESULTS: Follow-up information was available in 95/116 children and 154/187 young
      adults. Median follow-up of survivors was 6.9 years (interquartile range 4.7-9.4)
      and did not differ between the groups (p = 0.122). Long-term functional outcome
      was similar (p = 0.896): 53 (56%) children and 84 (55%) young adults had a
      favorable outcome (modified Rankin Scale 0-1). Mortality in children was 14%
      (13/95) and in young adults 7% (11/154) (p = 0.121) and recurrence rate did not
      differ (p = 0.759). Overall psychosocial impairment and quality of life did not
      differ, except for more behavioral problems among children (13% vs 5%, p = 0.040)
      and more frequent reports of an impact of AIS on everyday life among adults (27%
      vs 64%, p < 0.001). In a multivariate regression analysis, low Pediatric NIH
      Stroke Scale/NIH Stroke Scale score was the most important predictor of favorable
      outcome (p < 0.001). CONCLUSION: There were no major differences in long-term
      outcome after AIS in children and young adults for mortality, disability, quality
      of life, psychological, or social variables.

PMID- 25862798
TI  - Complications and mortality in hereditary hemorrhagic telangiectasia: A
      population-based study.
AB  - OBJECTIVES: Studies report that the risks of significant neurologic complications
      (including stroke, cerebral abscess, and migraine) and hemorrhagic sequelae are
      high in patients with hereditary hemorrhagic telangiectasia (HHT), and that life
      expectancy in this cohort is reduced. However, most published cohorts derive from
      specialist centers, which may be susceptible to bias. METHODS: We used a
      population-based approach to estimate the risks of developing neurologic and
      hemorrhagic complications of HHT, the association of a diagnosis of HHT with
      common cardiovascular and malignant comorbidities, and also long-term survival of
      those with the disease. RESULTS: From a UK primary care database of 3.5 million
      patients (The Health Improvement Network), we identified 675 cases with a
      diagnosis of HHT and compared them with 6,696 controls matched by age, sex, and
      primary care practice. Risks of stroke (odds ratio [OR] 1.8, 95% confidence
      interval [CI] 1.2-2.6), cerebral abscess (OR 30.0, CI 3.1-288), and migraine (OR
      1.7, CI 1.3-2.2) were elevated over controls. Bleeding complications including
      epistaxis (OR 11.6, CI 9.1-14.7) and gastrointestinal hemorrhage (OR 6.1, CI 2.8
      13.4) were more common in cases with HHT. Survival of cases with HHT was poorer
      than controls with a hazard ratio for death of 2.0 (CI 1.6-2.6) and a median age
      at death 3 years younger. CONCLUSIONS: Patients with HHT are at substantially
      increased risk of serious neurologic and hemorrhagic complications of the
      disease. Because a diagnosis of HHT is associated with a significantly poorer
      survival compared with those who have no disease, evaluation of new strategies to
      improve clinical management is required.

PMID- 25862799
TI  - Prognosis after spinal cord and cauda compression in spontaneous spinal epidural
      hematomas.
AB  - OBJECTIVE: Spontaneous spinal epidural hemorrhage (SSEH) warrants urgent surgical
      treatment in most cases. Which patients will benefit most from decompression is
      not known and the disease's rarity hampers the collection of large data series to
      ascertain this. Therefore, using an individual patient data (IPD) meta-analysis,
      we aimed to identify predictors for outcome and to obtain knowledge on the
      etiology of SSEH. METHODS: The IPD meta-analysis is based on raw data from case
      reports across all studies concerning all variables of interest. The Preferred
      Reporting Items for Systematic Reviews and Meta-Analyses statement was used. This
      led to a total of 741 unique pure SSEH patient cases from 487 journal articles.
      Data were extracted using a data extraction sheet and analyzed using a
      multivariable logistic regression model. RESULTS: A preoperative Frankel score of
      C and higher, absence of use of anticoagulants, compression of the cauda equina
      only, and the extension of the hematoma over 3 or 4 vertebral segments were
      associated with good outcome. Operative interval was not invariably associated
      with outcome and hypertension was not a risk factor for developing SSEH.
      CONCLUSIONS: Outcome is mainly determined by severity of preoperative neurologic
      deficit and use of anticoagulants. Evidence for a venous origin of SSEH is
      abundant in view of the observed anatomical distribution in different age
      categories and the absence of hypertension as an isolated risk factor.

PMID- 25862801
TI  - White matter lesion volume reduces fine motor skills: Is primary stroke
      prophylaxis warranted?

PMID- 25862800
TI  - Effect of white matter lesions on manual dexterity in healthy middle-aged
      persons.
AB  - OBJECTIVES: We hypothesized that integrated motor-visual functions measured by
      manipulative manual dexterity are affected by white matter lesion (WML) burden as
      measured on cranial MRI across relevant brain regions in subjects at risk of
      preclinical occult vascular disease. METHODS: A real-time cross-sectional study
      of healthy subjects aged 29 to 74 years with a family history of early-onset
      coronary artery disease (n = 714; mean age, 51 +/- 11 years; mean education, 14
      +/- 3 years; 42% male; 38% black) were identified from probands with coronary
      artery disease diagnosed before age 60 years. WMLs on 3-tesla brain MRI and
      Grooved Pegboard scores were measured. RESULTS: WMLs were observed at all ages.
      Mean pegboard scores were 108 +/- 18, similar to normal populations. In
      unadjusted analysis, WMLs and pegboard scores were significantly correlated by
      region (total WMLs, r = 0.34, p = 0.0001; frontal [r = 0.34, p < 0.0001], insula
      [r = 0.31, p < 0.0001], parietal [r = 0.31, p < 0.0001], and temporal [r = 0.17,
      p < 0.0001]). In multivariate analysis predicting (log) pegboard score adjusted
      for age, sex, race, education, regional or total volumes, and familial non
      independence, total WML volume (p = 5.79E - 05) and regional WML volumes (p <
      0.01) retained statistical significance in all but the youngest age quartile (29
      43 years). CONCLUSIONS: Greater WML volumes in different brain regions are
      associated with higher pegboard scores (worse performance) independent of age,
      sex, race, education, and total or regional volumes. This suggests that small
      vessel cerebrovascular disease may be present in healthy individuals in a
      preclinical state with measurable impact on complex integrative functions in
      individuals with excess risk of clinical vascular disease.

PMID- 25862802
TI  - Long-term improvement of tremor and ataxia after bilateral DBS of VoP/zona
      incerta in FXTAS.

PMID- 25862804
TI  - Tuberculosis: a medical evergreen.

PMID- 25862803
TI  - HIV status and the risk of ischemic stroke among men.
AB  - OBJECTIVE: Given conflicting data regarding the association of HIV infection and
      ischemic stroke risk, we sought to determine whether HIV infection conferred an
      increased ischemic stroke risk among male veterans. METHODS: The Veterans Aging
      Cohort Study-Virtual Cohort consists of HIV-infected and uninfected veterans in
      care matched (1:2) for age, sex, race/ethnicity, and clinical site. We analyzed
      data on 76,835 male participants in the Veterans Aging Cohort Study-Virtual
      Cohort who were free of baseline cardiovascular disease. We assessed
      demographics, ischemic stroke risk factors, comorbid diseases, substance use, HIV
      biomarkers, and incidence of ischemic stroke from October 1, 2003, to December
      31, 2009. RESULTS: During a median follow-up period of 5.9 (interquartile range
      3.5-6.6) years, there were 910 stroke events (37.4% HIV-infected). Ischemic
      stroke rates per 1,000 person-years were higher for HIV-infected (2.79, 95%
      confidence interval 2.51-3.10) than for uninfected veterans (2.24 [2.06-2.43])
      (incidence rate ratio 1.25 [1.09-1.43]; p < 0.01). After adjusting for
      demographics, ischemic stroke risk factors, comorbid diseases, and substance use,
      the risk of ischemic stroke was higher among male veterans with HIV infection
      compared with uninfected veterans (hazard ratio 1.17 [1.01-1.36]; p = 0.04).
      CONCLUSIONS: HIV infection is associated with an increased ischemic stroke risk
      among HIV-infected compared with demographically and behaviorally similar
      uninfected male veterans.

PMID- 25862807
TI  - Changes in Perceptions of Opioids Before and After Admission to Palliative Care
      Units in Japan: Results of a Nationwide Bereaved Family Member Survey.
AB  - This study aimed to clarify perspectives of bereaved family members regarding
      opioids and compare perceptions before admission and after bereavement. A cross
      sectional questionnaire survey for bereaved family members in 100 inpatient
      palliative care units was administered. Participants were 297 bereaved family
      members of patients who used opioids. Many bereaved family members had
      misconceptions of opioids before admission. There was improvement after
      bereavement, but understanding remained low. Respondents less than 65 years old
      showed significantly greater decreases in misconceptions regarding opioids
      compared to older generations, after bereavement. Bereaved family members who
      were misinformed about opioids by physicians were significantly more likely to
      have misconceptions about opioids. Educational interventions for physicians are
      needed to ensure that they offer correct information to the general population. 

PMID- 25862808
TI  - The positively charged region of the myosin IIC non-helical tailpiece promotes
      filament assembly.

PMID- 25862809
TI  - Diet-induced hypercholesterolemia imparts structure-function changes to
      erythrocyte chondroitin sulphate/dermatan sulphate.
AB  - Hypercholesterolemia is one of the factors contributing to cardiovascular
      problems. Erythrocytes are known to contribute its cholesterol to atherosclerotic
      plaque. Our earlier study showed that erythrocytes overexpress chondroitin
      sulphate/dermatan sulphate (CS/DS), a linear co-polymer, during diabetes which
      resulted in increased cytoadherence to extracellular matrix (ECM) components.
      This study was carried out to determine whether diet-induced hypercholesterolemia
      had any effect on erythrocyte CS/DS and impacted cytoadherence to ECM components.
      Unlike in diabetes, diet-induced hypercholesterolemia did not show quantitative
      changes in erythrocyte CS/DS but showed difference in proportion of un-sulphated
      and 4-O-sulphated disaccharides. Erythrocytes from hypercholesterolemic rats
      showed increased adhesion to ECM components which was abrogated to various
      extents when subjected to chondroitinase ABC digestion. However, isolated CS/DS
      chains showed a different pattern of binding to ECM components indicating that
      orientation of CS/DS chains could be playing a role in binding. 

PMID- 25862810
TI  - MicroRNAs as the fine-tuners of Src oncogenic signalling.
AB  - The cellular Src (c-Src) tyrosine kinase is upregulated and believed to play a
      pivotal role in various human cancers. However, the molecular mechanism
      underlying c-Src-mediated tumour progression remains elusive. Recent studies have
      revealed that several microRNAs (miRNAs) function as tumour suppressors by
      regulating the malignant expression of signalling molecules. Aberrant expression
      of miRNAs is frequently observed in human cancers and should be exploited to seek
      related molecular targets. In this review, we focus on miRNAs found to be
      involved in Src signalling in various cancers. We summarize recent findings on
      Src-related miRNAs, their target genes, mechanisms behind their interplay and
      their implications for cancer therapeutics. 

PMID- 25862811
TI  - Preoperative serum-gamma-glutamyltransferase (GGT) does not represent an
      independent prognostic factor in a European cohort of patients with non
      metastatic renal cell carcinoma.
AB  - AIMS: Increasing evidence suggests that the serum-gamma-glutamyltransferase (GGT)
      might correlate with tumour development and growth rates in various human cancer
      types. Thus, we decided to investigate the potential prognostic impact of the
      preoperatively assessed serum-GGT in a European cohort of patients with non
      metastatic renal cell carcinoma (RCC). METHODS: Clinicopathological data from 700
      consecutive patients with non-metastatic RCC, operated between 2000 and 2010 at a
      single tertiary academic centre, were evaluated retrospectively. Preoperative
      serum-GGT was assessed 1 day before surgery. Patients were categorised using a
      serum-GGT cut-off value of 40 U/L according to a calculation by receiver
      operating curve analysis. Patients' cancer-specific survival (CSS), metastasis
      free survival (MFS), as well as overall survival (OS) were assessed using the
      Kaplan-Meier method and Cox proportional models. RESULTS: In univariate analysis,
      an elevated preoperative serum-GGT level (<40 U/L vs >=40 U/L) was statistically
      significantly associated with a shorter MFS (HR=1.517, 95% CI 1.047 to 2.197,
      p=0.027). In multivariate analyses, pathological T-Stage (pT-1 vs pT-2-4,
      HR=2.065, 95% CI 1.665 to 2.560), tumour grade (G-1+G-2 vs G-3+G-4, HR=1.671, 95%
      CI 1.261 to 2.213), as well as the presence of histological tumour necrosis (No
      vs Yes, HR=2.031, 95% CI 1.355 to 3.046) were independent predictors of MFS in
      patients with RCC, whereas the preoperative serum-GGT failed to reach independent
      predictor status (<40 U/L vs >=40 U/L, HR=1.156, 95% CI 0.791 to 1.690). No
      prognostic role for GGT in OS or CSS could be identified. CONCLUSIONS: In the
      cohort studied, patients with an elevated (>=40 U/L) preoperative serum-GGT had a
      subsequently shorter MFS only in univariate analysis. In contrast to previous
      studies, our data failed to demonstrate preoperatively assessed serum-GGT as an
      independent prognostic factor in patients with non-metastatic RCC.

PMID- 25862812
TI  - A retrospective study of patients with follicular lymphoma (FL): identification
      of in situ FL or FL-like B cells of uncertain significance in lymph nodes
      resected at the time of previous surgery for carcinomas.
AB  - BACKGROUND AND AIMS: In situ follicular lymphoma (iFL)/intrafollicular neoplasia
      and follicular lymphoma (FL)-like B cells of uncertain significance represent
      proliferation of Bcl-2/t(14;18)-positive B cells solely in the germinal centres.
      The condition is interpreted as an early event in the multi-step lymphomagenesis
      of FL. The aim of this study is to examine the issue more specifically. METHODS:
      We reviewed medical history of FL patients in whom thoracoabdominal surgery with
      lymphadenectomy had been performed for management of carcinomas. These previously
      resected lymph nodes as well as the current FL nodes were analysed by
      immunohistochemistry, fluorescent in situ hybridisation, and PCR amplification
      with direct sequencing. RESULTS: We studied four such FL patients from a total of
      150 patients with FL; all had iFL in the previously resected lymph nodes. Clonal
      relation was verified and suggested in one case each. The time from
      lymphadenectomy to the diagnosis of FL was 23-120 months. There appeared to be a
      reverse correlation between the rate of Bcl-2-positive follicle proliferation and
      the time from surgery to diagnosis of FL. CONCLUSIONS: Although the rate for
      development of FL in individuals having iFL has been reported to be low from
      prospective studies, the present data indicate that follow-up studies for a
      longer period is necessary; the rate of Bcl-2-positive follicle proliferation
      could be a factor to predict development of FL in prospective studies. Such a
      retrospective study may contribute to elucidate mechanism(s) involved in
      lymphomagenesis of FL.

PMID- 25862813
TI  - Intestinal Epithelial TLR-4 Activation Is Required for the Development of Acute
      Lung Injury after Trauma/Hemorrhagic Shock via the Release of HMGB1 from the Gut.
AB  - The mechanisms that lead to the development of remote lung injury after trauma
      remain unknown, although a central role for the gut in the induction of lung
      injury has been postulated. We hypothesized that the development of remote lung
      injury after trauma/hemorrhagic shock requires activation of TLR4 in the
      intestinal epithelium, and we sought to determine the mechanisms involved. We
      show that trauma/hemorrhagic shock caused lung injury in wild-type mice, but not
      in mice that lack TLR4 in the intestinal epithelium, confirming the importance of
      intestinal TLR4 activation in the process. Activation of intestinal TLR4 after
      trauma led to increased endoplasmic reticulum (ER) stress, enterocyte apoptosis,
      and the release of circulating HMGB1, whereas inhibition of ER stress attenuated
      apoptosis, reduced circulating HMGB1, and decreased lung injury severity.
      Neutralization of circulating HMGB1 led to reduced severity of lung injury after
      trauma, and mice that lack HMGB1 in the intestinal epithelium were protected from
      the development of lung injury, confirming the importance of the intestine as the
      source of HMGB1, whose release of HMGB1 induced a rapid protein kinase C zeta
      mediated internalization of surface tight junctions in the pulmonary epithelium.
      Strikingly, the use of a novel small-molecule TLR4 inhibitor reduced intestinal
      ER stress, decreased circulating HMGB1, and preserved lung architecture after
      trauma. Thus, intestinal epithelial TLR4 activation leads to HMGB1 release from
      the gut and the development of lung injury, whereas strategies that block
      upstream TLR4 signaling may offer pulmonary protective strategies after trauma. 

PMID- 25862814
TI  - Chemical attenuation of Plasmodium in the liver modulates severe malaria disease
      progression.
AB  - Cerebral malaria is one of the most severe complications of malaria disease,
      attributed to a complicated series of immune reactions in the host. The syndrome
      is marked by inflammatory immune responses, margination of leukocytes, and
      parasitized erythrocytes in cerebral vessels leading to breakdown of the blood
      brain barrier. We show that chemical attenuation of the parasite at the very
      early, clinically silent liver stage suppresses parasite development, delays the
      time until parasites establish blood-stage infection, and provokes an altered
      host immune response, modifying immunopathogenesis and protecting from cerebral
      disease. The early response is proinflammatory and cell mediated, with increased
      T cell activation in the liver and spleen, and greater numbers of effector T
      cells, cytokine-secreting T cells, and proliferating, proinflammatory cytokine
      producing T cells. Dendritic cell numbers, T cell activation, and infiltration of
      CD8(+) T cells to the brain are decreased later in infection, possibly mediated
      by the anti-inflammatory cytokine IL-10. Strikingly, protection can be
      transferred to naive animals by adoptive transfer of lymphocytes from the spleen
      at very early times of infection. Our data suggest that a subpopulation belonging
      to CD8(+) T cells as early as day 2 postinfection is responsible for protection.
      These data indicate that liver stage-directed early immune responses can moderate
      the overall downstream host immune response and modulate severe malaria outcome. 

PMID- 25862815
TI  - DEC205+ Dendritic Cell-Targeted Tolerogenic Vaccination Promotes Immune Tolerance
      in Experimental Autoimmune Arthritis.
AB  - Previous studies in mouse models of autoimmune diabetes and encephalomyelitis
      have indicated that the selective delivery of self-antigen to the endocytic
      receptor DEC205 on steady-state dendritic cells (DCs) may represent a suitable
      approach to induce Ag-specific immune tolerance. In this study, we aimed to
      examine whether DEC205(+) DC targeting of a single immunodominant peptide derived
      from human cartilage proteoglycan (PG) can promote immune tolerance in PG-induced
      arthritis (PGIA). Besides disease induction by immunization with whole PG protein
      with a high degree of antigenic complexity, PGIA substantially differs from
      previously studied autoimmune models not only in the target tissue of autoimmune
      destruction but also in the nature of pathogenic immune effector cells. Our
      results show that DEC205(+) DC targeting of the PG peptide 70-84 is sufficient to
      efficiently protect against PGIA development. Complementary mechanistic studies
      support a model in which DEC205(+) DC targeting leads to insufficient germinal
      center B cell support by PG-specific follicular helper T cells. Consequently,
      impaired germinal center formation results in lower Ab titers, severely
      compromising the development of PGIA. Overall, this study further corroborates
      the potential of prospective tolerogenic DEC205(+) DC vaccination to interfere
      with autoimmune diseases, such as rheumatoid arthritis. 

PMID- 25862816
TI  - Polycomb Repressive Complex 2 Confers BRG1 Dependency on the CIITA Locus.
AB  - CIITA (or MHC2TA) coordinates constitutive and IFN-gamma-induced expression of
      MHC class II genes. IFN-gamma responsiveness of CIITA requires BRG1 (SMARCA4),
      the ATPase engine of the chromatin remodeling SWI/SNF complex (also called BAF).
      SWI/SNF is defective in many human cancers, providing a mechanism to explain IFN
      gamma resistance. BRG1 dependency is mediated through remote elements. Short
      CIITA reporters lacking these elements respond to IFN-gamma, even in BRG1
      deficient cells, suggesting that BRG1 counters a remote repressive influence. The
      nature of this distal repressor is unknown, but it would represent a valuable
      therapeutic target to reactivate IFN-gamma responsiveness in cancer. In this
      article, we show that the polycomb repressive complex 2 (PRC2) components EZH2
      and SUZ12, as well as the associated histone mark H3K27me3, are codetected at
      interenhancer regions across the CIITA locus. IFN-gamma caused a BRG1-dependent
      reduction in H3K27me3, associated with nucleosome displacement. SUZ12 knockdown
      restored IFN-gamma responsiveness in BRG1-null cells, and it mimicked the ability
      of BRG1 to induce active histone modifications (H3K27ac, H3K4me) at the -50-kb
      enhancer. Thus, PRC2 confers BRG1 dependency on the CIITA locus. Our data suggest
      that, in addition to its known roles in promoting stemness and proliferation,
      PRC2 may inhibit immune surveillance, and it could be targeted to reactivate
      CIITA expression in SWI/SNF deficient cancers. 

PMID- 25862817
TI  - Obesity Increases Mortality and Modulates the Lung Metabolome during Pandemic
      H1N1 Influenza Virus Infection in Mice.
AB  - Obese individuals are at greater risk for hospitalization and death from
      infection with the 2009 pandemic H1N1 influenza virus (pH1N1). In this study,
      diet-induced and genetic-induced obese mouse models were used to uncover
      potential mechanisms by which obesity increases pH1N1 severity. High-fat diet
      induced and genetic-induced obese mice exhibited greater pH1N1 mortality, lung
      inflammatory responses, and excess lung damage despite similar levels of viral
      burden compared with lean control mice. Furthermore, obese mice had fewer
      bronchoalveolar macrophages and regulatory T cells during infection. Obesity is
      inherently a metabolic disease, and metabolic profiling has found widespread
      usage in metabolic and infectious disease models for identifying biomarkers and
      enhancing understanding of complex mechanisms of disease. To further characterize
      the consequences of obesity on pH1N1 infection responses, we performed global
      liquid chromatography-mass spectrometry metabolic profiling of lung tissue and
      urine. A number of metabolites were perturbed by obesity both prior to and during
      infection. Uncovered metabolic signatures were used to identify changes in
      metabolic pathways that were differentially altered in the lungs of obese mice
      such as fatty acid, phospholipid, and nucleotide metabolism. Taken together,
      obesity induces distinct alterations in the lung metabolome, perhaps contributing
      to aberrant pH1N1 immune responses. 

PMID- 25862819
TI  - Protective Role of STAT6 in Basophil-Dependent Prurigo-like Allergic Skin
      Inflammation.
AB  - Prurigo is a common, but treatment-resistant, skin disease characterized by
      persistent papules/nodules and severe itching. Prurigo occurs in association with
      various underlying diseases, such as diabetes, chronic renal failure, and
      internal malignancies. Atopic dermatitis is occasionally complicated by prurigo
      lesions. However, the pathology of prurigo is completely undefined. We
      demonstrate that repeated intradermal administration of Ag to IgE-transgenic mice
      causes persistent and pruritic papulonodular skin lesions mimicking prurigo. Skin
      lesions were histopathologically characterized by irregular acanthosis and dermal
      cellular infiltrates comprising eosinophils, mononuclear cells, and basophils,
      with epidermal nerve fiber sprouting. In vivo depletion of basophils alleviated
      skin reactions, indicating that the inflammation is basophil dependent.
      Unexpectedly, STAT6 signaling was unnecessary for skin lesion development if IgE
      was present. Moreover, the absence of STAT6 signaling exacerbated the
      inflammation, apparently as the result of impaired generation of an M2-type anti
      inflammatory macrophage response. These results provide novel insights into the
      pathologic mechanisms underlying prurigo. Although basophils are indispensable
      for prurigo-like inflammation, Th2 immunity mediated by STAT6 appears to play a
      protective role, and therapies targeting Th2-type cytokines may risk aggravating
      the inflammation. 

PMID- 25862818
TI  - SCARB2/LIMP-2 Regulates IFN Production of Plasmacytoid Dendritic Cells by
      Mediating Endosomal Translocation of TLR9 and Nuclear Translocation of IRF7.
AB  - Scavenger receptor class B, member 2 (SCARB2) is essential for endosome
      biogenesis and reorganization and serves as a receptor for both beta
      glucocerebrosidase and enterovirus 71. However, little is known about its
      function in innate immune cells. In this study, we show that, among human
      peripheral blood cells, SCARB2 is most highly expressed in plasmacytoid dendritic
      cells (pDCs), and its expression is further upregulated by CpG
      oligodeoxynucleotide stimulation. Knockdown of SCARB2 in pDC cell line GEN2.2
      dramatically reduces CpG-induced type I IFN production. Detailed studies reveal
      that SCARB2 localizes in late endosome/lysosome of pDCs, and knockdown of SCARB2
      does not affect CpG oligodeoxynucleotide uptake but results in the retention of
      TLR9 in the endoplasmic reticulum and an impaired nuclear translocation of IFN
      regulatory factor 7. The IFN-I production by TLR7 ligand stimulation is also
      impaired by SCARB2 knockdown. However, SCARB2 is not essential for influenza
      virus or HSV-induced IFN-I production. These findings suggest that SCARB2
      regulates TLR9-dependent IFN-I production of pDCs by mediating endosomal
      translocation of TLR9 and nuclear translocation of IFN regulatory factor 7. 

PMID- 25862820
TI  - Syk tyrosine kinase is critical for B cell antibody responses and memory B cell
      survival.
AB  - Signals from the BCR are required for Ag-specific B cell recruitment into the
      immune response. Binding of Ag to the BCR induces phosphorylation of immune
      receptor tyrosine-based activation motifs in the cytoplasmic domains of the CD79a
      and CD79b signaling subunits, which subsequently bind and activate the Syk
      protein tyrosine kinase. Earlier work with the DT40 chicken B cell leukemia cell
      line showed that Syk was required to transduce BCR signals to proximal activation
      events, suggesting that Syk also plays an important role in the activation and
      differentiation of primary B cells during an immune response. In this study, we
      show that Syk-deficient primary mouse B cells have a severe defect in BCR-induced
      activation, proliferation, and survival. Furthermore, we demonstrate that Syk is
      required for both T-dependent and T-independent Ab responses, and that this
      requirement is B cell intrinsic. In the absence of Syk, Ag fails to induce
      differentiation of naive B cells into germinal center B cells and plasma cells.
      Finally, we show that the survival of existing memory B cells is dependent on
      Syk. These experiments demonstrate that Syk plays a critical role in multiple
      aspects of B cell Ab responses. 

PMID- 25862822
TI  - Erratum for Wire et al., Lack of clinically significant pharmacokinetic
      interaction between the thrombopoietin receptor agonist eltrombopag and hepatitis
      C virus protease inhibitors boceprevir and telaprevir.

PMID- 25862824
TI  - Efficacy and safety of docetaxel and prednisolone for castration-resistant
      prostate cancer: a multi-institutional retrospective study in Japan.
AB  - OBJECTIVE: Although some new drugs for castration-resistant prostate cancer are
      available, docetaxel still plays an important role in castration-resistant
      prostate cancer treatment. In this study, we evaluated the efficacy and safety of
      docetaxel and prednisolone in patients with castration-resistant prostate cancer.
      METHODS: We conducted a retrospective chart review of castration-resistant
      prostate cancer patients who received docetaxel and prednisolone at 14 hospitals
      in the Sapporo Medical University Urologic Oncology Consortium from August 2004
      to December 2011. RESULTS: A total of 140 patients with castration-resistant
      prostate cancer received docetaxel and prednisolone (median age, 73.8 years;
      median prostate specific antigen, 54.7 ng/ml). A median of six cycles (range: 1
      43) of docetaxel and prednisolone was administered per patient. Median follow-up
      was 13.7 months. Median overall survival was 22.0 months. The log-rank test
      revealed that prostate specific antigen before docetaxel and prednisolone (<50
      ng/ml) and the prostate specific antigen reduction rate (>=30%) were associated
      with overall survival (P < 0.001 and P < 0.001, respectively). Eighty patients
      (57.1%) achieved a prostate specific antigen reduction rate of over 30%. All
      except two (97.5%) reached 30% prostate specific antigen reduction within five
      cycles of docetaxel and prednisolone. There were two (1.4%) treatment-related
      deaths due to adverse events, which were interstitial lung disease, and febrile
      neutropenia and bacterial pneumonia. Interstitial lung disease occurred in 14
      (10.0%) patients within a median of 2.5 cycles of docetaxel and prednisolone.
      Grade 5 interstitial lung disease was seen after three cycles of docetaxel and
      prednisolone. CONCLUSIONS: If a prostate specific antigen reduction rate of over
      30% is not obtained within five cycles of docetaxel and prednisolone, other
      treatment options should be considered. Although most patients safely received
      docetaxel and prednisolone, we must always keep interstitial lung disease in mind
      as a possible lethal adverse event.

PMID- 25862821
TI  - T Cell Immunity to the Alkyl Hydroperoxide Reductase of Burkholderia
      pseudomallei: A Correlate of Disease Outcome in Acute Melioidosis.
AB  - There is an urgent need for a better understanding of adaptive immunity to
      Burkholderia pseudomallei, the causative agent of melioidosis that is frequently
      associated with sepsis or death in patients in Southeast Asia and Northern
      Australia. The imperative to identify vaccine targets is driven both by the
      public health agenda in these regions and biological threat concerns. In several
      intracellular bacterial pathogens, alkyl hydroperoxidase reductases are
      upregulated as part of the response to host oxidative stress, and they can
      stimulate strong adaptive immunity. We show that alkyl hydroperoxidase reductase
      (AhpC) of B. pseudomallei is strongly immunogenic for T cells of 'humanized' HLA
      transgenic mice and seropositive human donors. Some T cell epitopes, such as p6,
      are able to bind diverse HLA class II heterodimers and stimulate strong T cell
      immunity in mice and humans. Importantly, patients with acute melioidosis who
      survive infection show stronger T cell responses to AhpC relative to those who do
      not. Although the sequence of AhpC is virtually invariant among global B.
      pseudomallei clinical isolates, a Cambodian isolate varies only in C-terminal
      truncation of the p6 T cell epitope, raising the possibility of selection by host
      immunity. This variant peptide is virtually unable to stimulate T cell immunity.
      For an infection in which there has been debate about centrality of T cell
      immunity in defense, these observations support a role for T cell immunity to
      AhpC in disease protection. 

PMID- 25862825
TI  - Sexual satisfaction, anxiety, depression and quality of life among Turkish
      colorectal cancer patients [Izmir Oncology Group (IZOG) study].
AB  - OBJECTIVE: Determination of psychological problems will shed light on the terms
      of solution and provide support to patients about these problems will ensure the
      patients' coherence to the treatment and will enhance the benefits they receive
      from treatment. In this study, we aimed to determine these psychosocial problems
      and the interactions with each other in colon cancer patients. METHODS: In this
      study, 105 patients with colorectal cancer were included. The forms consist of
      sociodemographic features, Hospital Anxiety and Depression Scale, European
      Organization for Research on Treatment of Cancer Questionnaires Quality of Life
      C30 and Golombok-Rust Inventory of Sexual Satisfaction questionnaires. RESULTS:
      Male patients had significantly higher European Organization for Research on
      Treatment of Cancer Questionnaires Quality of Life-C30 function scales and global
      quality-of-life scores than female patients. Golombok-Rust Inventory of Sexual
      Satisfaction scores of female patients were significantly higher than that of
      male patients. European Organization for Research on Treatment of Cancer
      Questionnaires Quality of Life-C30 function scales and global quality-of-life
      scores of the patients with high depression scores were significantly lower,
      conversely symptom scale scores of the patients with high depression scores were
      significantly higher than that of the patients with low depression scores.
      Patients with low anxiety scores had significantly higher European Organization
      for Research on Treatment of Cancer Questionnaires Quality of Life-C30 function
      scales and global quality-of-life scores than the patients with high anxiety
      scores. Symptom scale scores of the patients with high anxiety scores were
      significantly higher than that of the patients with low anxiety scores. The
      scores of Golombok-Rust Inventory of Sexual Satisfaction except premature
      ejaculation and vaginismus were significantly higher in patients with high
      anxiety scores and a significant difference was determined in touch, avoidance
      and anorgasm. CONCLUSIONS: This study demonstrates that there is a significant
      association with anxiety/depression symptoms and quality-of-life scores, sexual
      dysfunction. Sexual dysfunction is significantly more common in patients with
      high anxiety and depression scores.

PMID- 25862826
TI  - Association between axillary lymph node status and Ki67 labeling index in triple
      negative medullary breast carcinoma.
AB  - OBJECTIVE: Medullary breast carcinoma is a rare breast carcinoma with good
      prognosis. Although it has been established that axillary lymph node metastasis
      is a poor prognostic factor, little is known about the relationship between
      axillary lymph node metastasis and clinicopathological characteristics of
      medullary breast carcinoma patients. The aim of this study was to identify
      factors that predict occurrence of axillary lymph node metastasis in medullary
      breast carcinoma patients. METHODS: We performed a retrospective study of
      axillary lymph node status and the relevant clinicopathological characteristics
      in 49 triple-negative medullary breast carcinoma patients with axillary lymph
      node dissection between November 2004 and July 2011. RESULTS: A total of 49
      patients were enrolled in the study. Fourteen patients (28.6%) had axillary lymph
      node metastasis that was confirmed pathologically. Axillary lymph node metastasis
      was not associated with age, menopausal status, primary tumor size or its
      location, the degree of inflammation within the tumor or mitotic count. However,
      we found a statistically significant association between axillary lymph node
      metastasis and Ki67 labeling index in primary tumors (P < 0.001). CONCLUSIONS:
      There is a positive association between Ki67 labeling index in the primary tumor
      and axillary lymph node metastasis in triple-negative medullary breast carcinoma
      patients.

PMID- 25862827
TI  - Echocardiography and invasive hemodynamics during stress testing for diagnosis of
      heart failure with preserved ejection fraction: an experimental study.
AB  - Inclusion of exercise testing in diagnostic guidelines for heart failure with
      preserved ejection fraction (HFpEF) has been advocated, but the target
      population, technical challenges, and underlying pathophysiological complexity
      raise difficulties to implementation. Hemodynamic stress tests may be feasible
      alternatives. Our aim was to test Trendelenburg positioning, phenylephrine, and
      dobutamine in the ZSF1 obese rat model to find echocardiographic surrogates for
      end-diastolic pressure (EDP) elevation and HFpEF. Seventeen-week-old Wistar
      Kyoto, ZSF1 lean, and obese rats (n = 7 each) randomly and sequentially underwent
      (crossover) Trendelenburg (30 degrees ), 5 MUg.Kg(-1).min(-1) dobutamine, and 7.5
      MUg.Kg(-1).min(-1) phenylephrine with simultaneous left ventricular (LV) pressure
      volume loop and echocardiography evaluation under halogenate anesthesia. Effort
      testing with maximum O2 consumption (Vo 2 max) determination was performed 1 wk
      later. Obese ZSF1 showed lower effort tolerance and Vo 2 max along with higher
      resting EDP. Both Trendelenburg and phenylephrine increased EDP, whereas
      dobutamine decreased it. Significant correlations were found between EDP and 1)
      peak early filling Doppler velocity of transmitral flow (E) to corresponding
      myocardial tissue Doppler velocity (E') ratio, 2) E to E-wave deceleration time
      (E/DT) ratio, and 3) left atrial area (LAA). Diagnostic efficiency of E/DT*LAA by
      receiver-operating characteristic curve analysis for elevation of EDP above a cut
      off of 13 mmHg during hemodynamic stress was high (area under curve, AUC = 0.95)
      but not higher than that of E/E' (AUC = 0.77, P = 0.15). Results in ZSF1 obese
      rats suggest that noninvasive echocardiography after hemodynamic stress induced
      by phenylephrine or Trendelenburg can enhance diagnosis of stable HFpEF and
      constitute an alternative to effort testing. 

PMID- 25862829
TI  - Tetrandrine reverses human cardiac myofibroblast activation and myocardial
      fibrosis.
AB  - Tetrandrine (TTD) is a calcium channel blocker with documented antifibrotic
      actions. In this study, for the first time, we identified that TTD can directly
      prevent in vitro human cardiac myofibroblast activation and limit in vivo
      myocardial fibrosis. In vitro, cardiac myofibroblasts from human atrial biopsies
      (N = 10) were seeded in three-dimensional collagen matrices. Cell-collagen
      constructs were exposed to transforming growth factor-beta1 (10 ng/ml), with or
      without TTD (1 and 5 MUM) for 48 h. Collagen gel contraction, myofibroblast
      activation (alpha-smooth muscle actin expression), expression of profibrotic
      mRNAs, and rate of collagen protein synthesis were compared. TTD decreased
      collagen gel contraction (79.7 +/- 1.3 vs 60.1 +/- 8.9%, P < 0.01), alpha-smooth
      muscle actin expression (flow cytometry), collagen synthesis ([(3)H]proline
      incorporation), and collagen mRNA expression. Cell viability was similar between
      groups (annexin positive cells: 1.7 vs. 1.4%). TTD inhibited collagen gel
      contraction in the presence of T-type and L-type calcium channel blockers, and
      the intracellular calcium chelator BAPTA-AM (15 MUM), suggesting that the
      observed effects are not mediated by calcium homeostasis. In vivo, Dahl salt
      sensitive hypertensive rats were treated with variable doses of TTD (by
      intraperitoneal injection over 4 wk) and compared with untreated controls (N =
      12). Systemic blood pressure was monitored by tail cuff. Myocardial fibrosis and
      left ventricular compliance were assessed by histology and passive pressure
      volume analysis. Myocardial fibrosis was attenuated compared with untreated
      controls (%collagen area: 9.4 +/- 7.3 vs 2.1 +/- 1.0%, P < 0.01). Left
      ventricular compliance was preserved. In conclusion, TTD reverses human cardiac
      myofibroblast activation and myocardial fibrosis, independent of calcium channel
      blockade. 

PMID- 25862828
TI  - Mechanosignaling in the vasculature: emerging concepts in sensing, transduction
      and physiological responses.
AB  - Cells are constantly exposed to mechanical forces that play a role in modulating
      cellular structure and function. The cardiovascular system experiences physical
      forces in the form of shear stress and stretch associated with blood flow and
      contraction, respectively. These forces are sensed by endothelial cells and
      cardiomyocytes and lead to responses that control vascular and cardiac
      homeostasis. This was highlighted at the Pan American Physiological Society
      meeting at Iguassu Falls, Brazil, in a symposium titled "Mechanosignaling in the
      Vasculature." This symposium presented recent research that showed the existence
      of a vital link between mechanosensing and downstream redox sensitive signaling
      cascades. This link helps to transduce and transmit the physical force into an
      observable physiological response. The speakers showcased how mechanosensors such
      as ion channels, membrane receptor kinases, adhesion molecules, and other
      cellular components transduce the force via redox signals (such as reactive
      oxygen species and nitric oxide) to receptors (transcription factors, growth
      factors, etc.). Receptor activated pathways then lead to cellular responses
      including cellular proliferation, contraction, and remodeling. These responses
      have major relevance to the physiology and pathophysiology of various
      cardiovascular diseases. Thus an understanding of the complex series of events,
      from the initial sensing through the final response, is essential for progress in
      this field. Overall, this symposium addressed some important emerging concepts in
      the field of mechanosignaling and the eventual pathophysiological responses. 

PMID- 25862830
TI  - Protein assemblies of sodium and inward rectifier potassium channels control
      cardiac excitability and arrhythmogenesis.
AB  - The understanding of how cardiac ion channels function in the normal and the
      diseased heart has greatly increased over the last four decades thanks to the
      advent of patch-clamp technology and, more recently, the emergence of genetics,
      as well as cellular and molecular cardiology. However, our knowledge of how these
      membrane-embedded proteins physically interact with each other within
      macromolecular complexes remains incomplete. This review focuses on how the main
      cardiac inward sodium channel (NaV1.5) and the strong inward rectifier potassium
      channel (Kir2.1) function within macromolecular complexes to control cardiac
      excitability. It has become increasingly clear that these two important ion
      channel proteins physically interact with multiple other protein partners and
      with each other from early stages of protein trafficking and targeting through
      membrane anchoring, recycling, and degradation. Recent findings include
      compartmentalized regulation of NaV1.5 channel expression and function through a
      PDZ (postsynaptic density protein, Drosophila disc large tumor suppressor, and
      zonula occludens-1 protein) domain-binding motif, and interaction of caveolin-3
      with Kir2.1 and ankyrin-G as a molecular platform for NaV1.5 signaling. At the
      cardiomyocyte membrane, NaV1.5 and Kir2.1 interact through at least two distinct
      PDZ domain-scaffolding proteins (synapse-associated protein-97 and alpha1
      syntrophin), thus modulating reciprocally their cell-surface expression at two
      different microdomains. Emerging evidence also shows that inheritable mutations
      in plakophilin-2, ankyrin-G, dystrophin, syntrophin, synapse-associated protein
      97, and caveolin-3, among others, modify functional expression and/or
      localization in the cardiac cell of NaV1.5, Kir2.1 or both to give rise to
      arrhythmogenic diseases. Unveiling the mechanistic underpinnings of
      macromolecular interactions should increase our understanding of inherited and
      acquired arrhythmogenic cardiac diseases and may lead to advances in therapy. 

PMID- 25862831
TI  - Right ventricular cyclic nucleotide signaling is decreased in hyperoxia-induced
      pulmonary hypertension in neonatal mice.
AB  - Pulmonary hypertension (PH) and right ventricular hypertrophy (RVH) affect 25-35%
      of premature infants with significant bronchopulmonary dysplasia (BPD),
      increasing morbidity and mortality. We sought to determine the role of
      phosphodiesterase 5 (PDE5) in the right ventricle (RV) and left ventricle (LV) in
      a hyperoxia-induced neonatal mouse model of PH and RVH. After birth, C57BL/6 mice
      were placed in room air (RA) or 75% O2 (CH) for 14 days to induce PH and RVH.
      Mice were euthanized at 14 days or recovered in RA for 14 days or 42 days prior
      to euthanasia at 28 or 56 days of age. Some pups received sildenafil or vehicle
      (3 mg.kg(-1).dose(-1) sc) every other day from P0. RVH was assessed by Fulton's
      index [RV wt/(LV + septum) wt]. PDE5 protein expression was analyzed via Western
      blot, PDE5 activity was measured by commercially available assay, and cGMP was
      measured by enzyme-linked immunoassay. Hyperoxia induced RVH in mice after 14
      days, and RVH did not resolve until 56 days of age. Hyperoxia increased PDE5
      expression and activity in RV, but not LV + S, after 14 days. PDE5 expression
      normalized by 28 days of age, but PDE5 activity did not normalize until 56 days
      of age. Sildenafil given during hyperoxia prevented RVH, decreased RV PDE5
      activity, and increased RV cGMP levels. Mice with cardiac-specific overexpression
      of PDE5 had increased RVH in RA. These findings suggest normal RV PDE5 function
      is disrupted by hyperoxia, and elevated PDE5 contributes to RVH and remodeling.
      Therefore, in addition to impacting the pulmonary vasculature, sildenafil also
      targets PDE5 in the neonatal mouse RV and decreases RVH. 

PMID- 25862832
TI  - Sympathoexcitation in ANG II-salt hypertension involves reduced SK channel
      function in the hypothalamic paraventricular nucleus.
AB  - Hypertension (HTN) resulting from subcutaneous infusion of ANG II and dietary
      high salt (HS) intake involves sympathoexcitation. Recently, we reported reduced
      small-conductance Ca(2+)-activated K(+) (SK) current and increased excitability
      of presympathetic neurons in the paraventricular nucleus (PVN) in ANG II-salt
      HTN. Here, we hypothesized that ANG II-salt HTN would be accompanied by altered
      PVN SK channel activity, which may contribute to sympathoexcitation in vivo. In
      anesthetized rats with normal salt (NS) intake, bilateral PVN microinjection of
      apamin (12.5 pmol/50 nl each), the SK channel blocker, remarkably elevated
      splanchnic sympathetic nerve activity (SSNA), renal sympathetic nerve activity
      (RSNA), and mean arterial pressure (MAP). In contrast, rats with ANG II-salt HTN
      demonstrated significantly attenuated SSNA, RSNA, and MAP (P < 0.05) responses to
      PVN-injected apamin compared with NS control rats. Next, we sought to examine the
      individual contributions of HS and subcutaneous infusion of ANG II on PVN SK
      channel function. SSNA, RSNA, and MAP responses to PVN-injected apamin in rats
      with HS alone were significantly attenuated compared with NS-fed rats. In
      contrast, sympathetic nerve activity responses to PVN-injected apamin in ANG II
      treated rats were slightly attenuated with SSNA, demonstrating no statistical
      difference compared with NS-fed rats, whereas MAP responses to PVN-injected
      apamin were similar to NS-fed rats. Finally, Western blot analysis showed no
      statistical difference in SK1-SK3 expression in the PVN between NS and ANG II
      salt HTN. We conclude that reduced SK channel function in the PVN is involved in
      the sympathoexcitation associated with ANG II-salt HTN. Dietary HS may play a
      dominant role in reducing SK channel function, thus contributing to
      sympathoexcitation in ANG II-salt HTN. 

PMID- 25862833
TI  - Exposure to medium and high ambient levels of ozone causes adverse systemic
      inflammatory and cardiac autonomic effects.
AB  - Epidemiological evidence suggests that exposure to ozone increases cardiovascular
      morbidity. However, the specific biological mechanisms mediating ozone-associated
      cardiovascular effects are unknown. To determine whether short-term exposure to
      ambient levels of ozone causes changes in biomarkers of cardiovascular disease
      including heart rate variability (HRV), systemic inflammation, and coagulability,
      26 subjects were exposed to 0, 100, and 200 ppb ozone in random order for 4 h
      with intermittent exercise. HRV was measured and blood samples were obtained
      immediately before (0 h), immediately after (4 h), and 20 h after (24 h) each
      exposure. Bronchoscopy with bronchoalveolar lavage (BAL) was performed 20 h after
      exposure. Regression modeling was used to examine dose-response trends between
      the endpoints and ozone exposure. Inhalation of ozone induced dose-dependent
      adverse changes in the frequency domains of HRV across exposures consistent with
      increased sympathetic tone [increase of (parameter estimate +/- SE) 0.4 +/- 0.2
      and 0.3 +/- 0.1 in low- to high-frequency domain HRV ratio per 100 ppb increase
      in ozone at 4 h and 24 h, respectively (P = 0.02 and P = 0.01)] and a dose
      dependent increase in serum C-reactive protein (CRP) across exposures at 24 h
      [increase of 0.61 +/- 0.24 mg/l in CRP per 100 ppb increase in ozone (P = 0.01)].
      Changes in HRV and CRP did not correlate with ozone-induced local lung
      inflammatory responses (BAL granulocytes, IL-6, or IL-8), but changes in HRV and
      CRP were associated with each other after adjustment for age and ozone level.
      Inhalation of ozone causes adverse systemic inflammatory and cardiac autonomic
      effects that may contribute to the cardiovascular mortality associated with short
      term exposure. 

PMID- 25862834
TI  - Bacillus anthracis edema but not lethal toxin challenge in rats is associated
      with depressed myocardial function in hearts isolated and tested in a Langendorff
      system.
AB  - Although direct myocardial depression has been implicated in the lethal effects
      of Bacillus anthracis lethal toxin (LT), in hearts isolated from healthy rats and
      perfused under constant pressure, neither LT or edema toxin (ET) in typically
      lethal concentrations depressed myocardial function. In the present study, we
      challenged rats with LT and ET and performed in vivo and ex vivo heart measures.
      Sprague-Dawley rats infused over 24 h with LT (n = 94), ET (n = 99), or diluent
      (controls; n = 50) were studied at 8, 24, or 48 h. Compared with control rats
      (all survived), survival rates with LT (56.1%) and ET (37.3%) were reduced (P <
      0.0001) similarly (P = 0.66 for LT vs. ET). LT decreased mean arterial blood
      pressure from 12 to 20 h (P <= 0.05), whereas ET decreased it progressively
      throughout (P < 0.05). On echocardiography, LT decreased left ventricular (LV)
      ejection fraction at 8 and 48 h but increased it at 24 h and decreased cardiac
      output (P <= 0.05 for the time interaction or averaged over time). ET decreased
      systolic and diastolic volumes and increased LV ejection fraction at 24 h (P <=
      0.05). In isolated hearts perfused for 120 min under constant pressure, LT did
      not significantly alter LV systolic or developed pressures at any time point,
      whereas ET decreased both of these at 24 h (P < 0.0001 initially). ET but not LT
      progressively increased plasma creatine phosphokinase and cardiac troponin levels
      (P < 0.05). In conclusion, despite echocardiographic changes, in vivo lethal LT
      challenge did not produce evidence of myocardial depression in isolated rat
      hearts. While lethal ET challenge did depress isolated heart function, this may
      have resulted from prior hypotension and ischemia. 

PMID- 25862836
TI  - Characterization of the 12q amplicons in lipomatous soft tissue tumors by
      multiplex ligation-dependent probe amplification-based copy number analysis.
AB  - BACKGROUND/AIM: Well-differentiated liposarcoma (WDLPS) and de-differentiated
      liposarcoma (DDLPS) are characterized by amplified sequences derived from the
      long arm of chromosome 12. The goal of the present study was to identify, besides
      the well-known candidate genes, novel relevant genes in these large, complex 12q
      amplicons. MATERIALS AND METHODS: Using multiplex ligation-dependent probe
      amplification, genetic alterations in 19 different genes of 12q12-24 were
      evaluated in 77 lipomatous soft tissue tumors (including lipomas, WDLPS, DDLPS
      and pleomorphic liposarcomas). RESULTS: We recorded several amplified genes of
      12q13-15, including miR-26a-2, a gene not well studied in liposarcoma, and the
      well-known and previously described genes murine double minute 2 (MDM2), YEATS
      domain-containing protein 4 (YEATS4), high-mobility AT-hook 2 (HMGA2), cyclin
      dependent kinase 4 (CDK4) and tetraspanin 31 (TSPAN31). Interestingly, the
      amplification profiles of these six genes were found to be significantly
      different between WDLPS and DDLPS, more frequently having a high-level status in
      DDLPS than in WDLPS. In addition, DDLPS were found to have significantly higher
      mean amplification ratios compared to WDLPS. Moreover, we identified additional
      genes exclusively amplified in DDLPS in 12q13, 12q21 and 12q24, including glioma
      associated oncogene homolog 1 (GLI1), mitogen activated protein kinase kinase
      kinase 12 (MAP3K12), cyclin-dependent kinase 2 (CDK2), ALX homeobox 1 (ALX1) and
      T-box 5 (TBX5). CONCLUSION: Differences in amplification profiles among WDLPS and
      DDLPS may be related to progression/de-differentiation in liposarcomas and show
      how in the future amplification profiles could provide an adjunctive tool in
      characterizing progression to DDLPS. In addition, we identified additional genes
      exclusively amplified in DDLPS, which may play a role in liposarcomagenesis,
      particularly in the de-differentiation process.

PMID- 25862835
TI  - Best anesthetics for assessing left ventricular systolic function by
      echocardiography in mice.
AB  - Our review of the literature of the major cardiovascular journals for the past
      three years showed that for all studies using anesthesia for mouse
      echocardiography, the predominant anesthetic was isoflurane, which was used in
      76% of the studies. The goal of this investigation was to determine if isoflurane
      is indeed the best anesthetic. Accordingly, we compared isoflurane with 2,2,2
      tribromoethanol (Avertin), ketamine-xylazine, and ketamine on different days in
      the same 14 mice, also studied in the conscious state without anesthesia. A
      randomized crossover study design was employed to compare the effects on left
      ventricular (LV) systolic function and heart rate of the four different
      anesthetic agents assessed by transthoracic echocardiography. As expected, each
      anesthetic depressed LV ejection fraction and heart rate when compared with
      values in conscious mice. Surprisingly, isoflurane was not the best, but actually
      second to last in maintaining normal LV function and heart rate. The anesthetic
      with the least effect on LV function and heart rate was ketamine alone at a dose
      of 150 mg/kg, followed by Avertin at 290 mg/kg, isoflurane at 3% induction and 1
      to 2% maintenance, and lastly ketamine-xylazine at 100 and 10 mg/kg,
      respectively. In summary, these results indicate that ketamine alone exerts the
      least depressant effects on LV function and heart rate, with Avertin second,
      suggesting that these anesthetics should be used when it is not feasible to study
      the animals in the conscious state as opposed to the most commonly used
      anesthetic, isoflurane. 

PMID- 25862837
TI  - The expression of Toll-like receptors 2, 4, 5, 7 and 9 in Merkel cell carcinoma.
AB  - AIM: We sought to clarify whether the expression of toll-like receptors (TLR) in
      Merkel cell carcinoma (MCC) is linked to tumor and patient characteristics,
      especially the presence of Merkel cell polyoma virus (MCV). MATERIALS AND
      METHODS: The study comprised of 128 patients with data on Merkel cell
      polyomavirus (MCV) status and clinical features were included in the study.
      Immunohistochemistry for TLR expression was performed on tissue microarray (TMA)
      slides. RESULTS: TLR 2, 4, 5, 7 and 9 expression was noted in most of the tumor
      specimens. Decreased expression of TLR 9 correlated strongly with MCV positivity.
      Cytoplasmic TLR 2 expression correlated with small tumor size, while nuclear TLR
      2 and TLR 5 expressions with larger tumors. Increased nuclear TLR 4 expression
      and decreased TLR 7 expression were associated with older age. CONCLUSION: TLR 2,
      4, 5, 7 and 9 appear to reflect certain clinicopathological variables and
      prognostic markers of MCC tumors.

PMID- 25862838
TI  - Synergistic growth inhibition of PC3 prostate cancer cells with low-dose
      combinations of simvastatin and alendronate.
AB  - The mevalonate pathway plays an important role in cancer biology and has been
      targeted with farnesyl transferase inhibitors, although their efficacy is limited
      due to significant adverse effects. Statins and bisphosphonates inhibit the
      mevalonate pathway at different steps, thus having negative effects at various
      levels on cancer cells. A combination of these drugs may result in an amplified
      cytotoxic effect and allow for use of significantly lower doses of the drugs
      involved. Statins inhibit the mevalonate pathway at 3-hydroxy-3-methylglutaryl
      coenzyme A reductase and bisphosphonates at farnesyl pyrophosphate synthase. Our
      results show that low-dose combinations of simvastatin and alendronate have a
      synergistic cytotoxic effect on androgen-independent prostate cancer PC-3 cells,
      but not on androgen-dependent LNCaP or DU 145 prostate cancer cells. These two
      drugs cause a sequential blockade of the mevalonate pathway and significantly
      affect survival and apoptotic pathways by down-regulating phospho-AKT and
      activating c-JUN and ERK. 

PMID- 25862839
TI  - Clinical significance of kallikrein-related peptidase-4 in oral cancer.
AB  - Kallikrein-related-peptidase-4 (KLK4), a serine protease originally discovered in
      developing tooth with broad target sequence specificity, serves vital functions
      in dental enamel formation. KLK4 is involved in degradation of extracellular
      matrix proteins and it is thought that this proteolytic activity could also
      promote tumor invasion and metastasis. Recent studies have associated KLK4
      expression with tumor progression and clinical outcome, particularly in prostate
      and ovarian cancer. Very little is known in regard KLK4 involvement in oral
      squamous cell carcinomas (OSCCs). Our objective was to investigate KLK4
      expression in OSCC pathogenesis and disease progression. KLK4 expression was
      evaluated by immunohistochemistry, western blots and zymograms in OSCC lines.
      Invasion assays using high versus low/undetectable KLK4-expressing OSCC cell
      lines were performed jointly with KLK4 siRNA inhibition. A large collection of
      OSCC specimens was evaluated for KLK4 expression and correlation with patients'
      characteristics and outcomes were determined. Our data indicate that KLK4 is
      differentially expressed in oral carcinomas. OSCC cell lines with high invasive
      and metastatic potential have the highest levels of KLK4 expression. KLK4 mRNA
      and protein expression correlated with enzyme activity detected by zymograms.
      Inhibition of KLK4 expression results in diminished invasive potential in OSCC
      cell lines. Consistently, KLK4 expression is stronger in primary tumors that
      later either recurred or developed metastases, suggesting that its preferential
      expression in OSCC might contribute to individual tumor biology. Therefore, this
      study provides supportive evidence in favor of a prognostic value for KLK4 in
      OSCC and suggests that KLK4 could serve as a potential therapeutic target in
      patients with oral cancer. 

PMID- 25862840
TI  - Effects of antioxidants and pro-oxidants on cytotoxicity of dihydroartemisinin to
      Molt-4 human leukemia cells.
AB  - BACKGROUND: The objective of the present study was to investigate how oxidative
      status influences the effectiveness of cytotoxicity of artemisinin towards cancer
      cells. It is hypothesized that antioxidants would reduce, whereas pro-oxidants
      would enhance, cytotoxicity. MATERIALS AND METHODS: Molt-4 human leukemia cells
      were incubated with vitamins C, E, D3, dexamethasone, or hydrogen peroxide alone
      or in combination with dihydroartemisinin (DHA). Concentrations of these
      compounds studied were similar to those achievable by oral administration. Viable
      cell counts were performed before (0 h) and at, 24 and 48 h after treatment.
      RESULTS: Vitamin C, vitamin D3, dexamethasone, and H2O2 caused significant Molt-4
      cell death. Vitamin E caused an increase in Molt-4 cell growth. Vitamin C and
      vitamin D3 significantly interacted with DHA at the 48-h time point and with H2O2
      at both 24-h and 48-h time points. CONCLUSION: Cellular oxidative status could
      alter the potency of artemisinin in killing cancer cells.

PMID- 25862841
TI  - Non-small cell lung cancer detection using microRNA expression profiling of
      bronchoalveolar lavage fluid and sputum.
AB  - AIM: To assess if miRNA expression profiling of bronchoalveolar lavage (BAL)
      fluid and sputum could be used to detect early-stage non-small cell lung cancer
      (NSCLC). MATERIALS AND METHODS: Hierarchical cluster analysis was performed on
      the expression levels of 5 miRNAs (miR-21, miR-143, miR-155, miR-210, and miR
      372) which were quantified using RNA reverse transcription and quantitative real
      time polymerase chain reaction in sputum and BAL samples from NSCLC cases and
      cancer-free controls. RESULTS: Cluster analysis of the miRNA expression levels in
      BAL samples from 21 NSCLC cases and sputum samples from 10 cancer-free controls
      yielded a diagnostic sensitivity of 85.7% and specificity of 100%. Cluster
      analysis of sputum samples from the same patients yielded a diagnostic
      sensitivity of 67.8% and specificity of 90%. CONCLUSION: miRNA expression
      profiling of sputum and BAL fluids represent a potential means to detect early
      stage NSCLC.

PMID- 25862842
TI  - Proliferating fibroblasts and HeLa cells co-cultured in vitro reciprocally
      influence growth patterns, protein expression, chromatin features and cell
      survival.
AB  - AIM: to identify biological interactions between proliferating fibroblasts and
      HeLa cells in vitro. MATERIALS AND METHODS: Fibroblasts were isolated from both
      normal and tumour human tissues. Coverslip co-cultures of HeLa and fibroblasts in
      various ratios with medium replacement every 48 h were studied using fixed cell
      staining with dyes such as Giemsa and silver staining, with immunochemistry for
      Ki-67 and E-cadherin, with dihydrofolate reductase (DHFR) enzyme reaction, as
      well as live cell staining for non-specific esterases and lipids. Other
      techniques included carmine cell labeling, autoradiography and apoptosis
      assessment. RESULTS: Under conditions of feeding and cell: cell ratios allowing
      parallel growth of human fibroblasts and HeLa cells, co-cultured for up to 20
      days, a series of phenomena occur consecutively: profound affinity between the
      two cell types and exchange of small molecules; encircling of the HeLa colonies
      by the fibroblasts and enhanced growth of both cell types at their contact areas;
      expression of carbonic anhydrase in both cell types and high expression of non
      specific esterases and cytoplasmic argyrophilia in the surrounding fibroblasts;
      intense production and secretion of lipid droplets by the surrounding
      fibroblasts; development of a complex net of argyrophilic projections of the
      fibroblasts; E-cadherin expression in the HeLa cells; from the 10th day onwards,
      an increasing detachment of batches of HeLa cells at the peripheries of colonies
      and appearance of areas with many multi-nucleated and apoptotic HeLa cells, and
      small HeLa fragments; from the 17th day, appearance of fibroblasts blocked at the
      G2-M phase. Co-cultures at approximately 17-20 days display a cell-cell fight
      with foci of (a) sparse growth of both cell types, (b) overgrowth of the
      fibroblasts and (c) regrowth of HeLa in small colonies. These results indicate
      that during their interaction with HeLa cells in vitro, proliferating fibroblasts
      can be activated against HeLa. This type of activation is not observed if
      fibroblast proliferation is blocked by contact inhibition of growth at
      confluency, or by omitting replacement of the nutrient medium. CONCLUSION: The
      present observations show that: (a) interaction between proliferating fibroblasts
      and HeLa cells in vitro drastically influences each other's protein expression,
      growth pattern, chromatin features and survival; (b) these functions depend on
      the fibroblast/HeLa ratio, cell topology (cell-cell contact and the architectural
      pattern developed during co-culture) and frequent medium change, as prerequisites
      for fibroblast proliferation; (c) this co-culture model is useful in the study of
      the complex processes within the tumour microenvironment, as well as the in vitro
      reproduction and display of several phenomena conventionally seen in tumour
      cytological sections, such as desmoplasia, apoptosis, nuclear abnormalities; and
      (d) overgrown fibroblasts adhering to the boundaries of HeLa colonies produce and
      secrete lipid droplets.

PMID- 25862843
TI  - Comparative characterization of stem cell marker expression, metabolic activity
      and resistance to doxorubicin in adherent and spheroid cells derived from the
      canine prostate adenocarcinoma cell line CT1258.
AB  - BACKGROUND: Canine prostate cancer represents a spontaneous animal model for the
      human counterpart. Cells with stem cell-like character are considered to play a
      major role in therapeutic resistance and tumor relapse. Thus, the identification
      of markers allowing for recognition and characterization of these cells is
      essential. MATERIALS AND METHODS: Expression of 12 stem cell marker genes in the
      canine prostate cancer cell line CT1258 and spheroid cells generated from these
      was analyzed by quantitative real-time PCR. In CT1258 and the generated spheroid
      cells, CD44 and CD133 expression was analyzed by flow cytometry, as well as
      proliferation and doxorubicin resistance. RESULTS: Integrin alpha-6 (ITGA6)
      expression and metabolic activity were significantly up-regulated in CT1258
      derived spheroid cells, while doxorubicin resistance remained comparable.
      CONCLUSION: ITGA6 de-regulation and metabolic activity appear to be
      characteristic of the generated spheres, indicating potential intervention
      targets.

PMID- 25862844
TI  - Quantitative structure-activity relationship and molecular docking of artemisinin
      derivatives to vascular endothelial growth factor receptor 1.
AB  - BACKGROUND/AIM: The antimalarial drug artemisinin has been shown to exert
      anticancer activity through anti-angiogenic effects. For further drug
      development, it may be useful to have derivatives with improved anti-angiogenic
      properties. MATERIAL AND METHODS: We performed molecular docking of 52
      artemisinin derivatives to vascular endothelial growth factor receptors (VEGFR1,
      VEGFR2), and VEGFA ligand using Autodock4 and AutodockTools-1.5.7.rc1 using the
      Lamarckian genetic algorithm. Quantitative structure-activity relationship (QSAR)
      analyses of the compounds prepared by Corina Molecular Networks were performed
      using the Molecular Operating Environment MOE 2012.10. RESULTS: A statistically
      significant inverse relationship was obtained between in silico binding energies
      to VEGFR1 and anti-angiogenic activity in vivo of a test-set of artemisinin
      derivatives (R=-0.843; p=0.035). This served as a control experiment to validate
      molecular docking predicting anti-angiogenc effects. Furthermore, 52 artemisinin
      derivatives were docked to VEGFR1 and in selected examples also to VEGFR2 and
      VEGFA. Higher binding affinities were calculated for receptors than for the
      ligand. The best binding affinities to VEGFR1 were found for an artemisinin
      dimer, 10-dihydroartemisinyl-2-propylpentanoate, and dihydroartemisinin alpha
      hemisuccinate sodium salt. QSAR analyses revealed significant relationships
      between VEGFR1 binding energies and defined molecular descriptors of 35
      artemisinins assigned to the training set (R=0.0848, p<0.0001) and 17 derivatives
      assigned to the test set (R=0.761, p<0.001). CONCLUSION: Molecular docking and
      QSAR calculations can be used to identify novel artemisinin derivatives with anti
      angiogenic effects.

PMID- 25862845
TI  - Formamidinodoxorubicins are more potent than doxorubicin as apoptosis inducers in
      human breast cancer cells.
AB  - BACKGROUND/AIM: The ability of five formamidinodoxorubicins to induce apoptosis
      of MCF-7 breast cancer cells was tested. All these compounds were modified at C
      3' and contain a formamidine group (-N=CH-NRR), with the rest of the cyclic
      secondary amine (HNRR) of a gradually increasing ring size. MATERIALS AND
      METHODS: Cytotoxicity was assessed using 3-(4,5-Dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide assay. To analyze apoptosis, double staining using
      fluorescence probes Hoechst 33258/propidium iodide (PI) and annexin V-
      Fluorescein isothiocyanate/PI was carried-out. Additionally, the TdT-mediated
      dUTP nick-end labelling test and activity of caspase 3 were determined. RESULTS:
      The four tested derivatives displayed a significant increase in antiproliferative
      activity in comparison to doxorubicin. All of the tested derivatives induced
      caspase-dependent apoptosis of MCF-7 cells. CONCLUSION: DOX-F MOR and DOX-F PAZ
      analogs are more potent apoptosis inducers than doxorubicin.

PMID- 25862846
TI  - Resistance to gemcitabine in the pancreatic cancer cell line KLM1-R reversed by
      metformin action.
AB  - BACKGROUND/AIM: The pancreatic cancer cell line KLM1 can gain chemoresistance
      following gemcitabine (GEM) treatment. Metformin was found to be a useful
      sensitising agent towards GEM treatment following gain of chemoresistance.
      MATERIALS AND METHODS: The proliferation of GEM-sensitive and -resistant cells
      was investigated over a range of metformin concentrations from 0.005 to 5 mM. The
      intra- and extra-cellular energetic profiles of these two cell types under
      metformin exposure were investigated through adenosine triphosphate (ATP) and L
      lactate assays. RESULTS: There was an unexpected decrease in intracellular L
      lactate following gain of chemoresistance, despite observable medium
      acidification. At the biochemical level, a marked effect on phosphorylated
      proteins upstream of Akt, along the mTOR pathway, was observed at 6 h. These
      changes followed a time-dependent pattern linked closely to the changes in the
      energetic profile. CONCLUSION: Together, these results indicate that metformin
      indirectly blocks protein phosphorylation, including that of heat shock protein
      27 (HSP27).

PMID- 25862847
TI  - Targeting mTOR and AREG with everolimus, sunitinib and sorafenib in HPV-positive
      and -negative SCC.
AB  - BACKGROUND/AIM: Head and neck squamous cell carcinoma (HNSCC) is an aggressive
      epithelial malignancy. It is the most common neoplasm appearing in the upper
      aerodigestive tract and the sixth most common cancer worldwide. The five-year
      survival rate remains poor despite advances in surgery, radiation and
      chemotherapy. Furthermore, the incidence of human papillomavirus (HPV)-associated
      oropharyngeal cancer is rising. Thus, innovative therapy approaches are
      imperative in order to improve the situation. Everolimus, an inhibitor of the
      mammalian target of rapamycin (mTOR) and sorafenib and sunitinib, multityrosine
      kinase inhibitors, have been notably effective in the therapy of different tumor
      entities. The modest side-effects and oral application of the drugs might improve
      patient compliance. Expression levels of mTOR and Amphiregulin (AREG) in p16
      positive and -negative SCC (squamous cell carcinoma) and the effect of
      everolimus, sorafenib or sunitinib on the expression levels of these target
      proteins were assessed. As far as we are aware of, this is one of the first in
      vitro studies to evaluate the effect of these small-molecule drugs with regard to
      the p16 status of SCC cells. MATERIALS AND METHODS: p16-negative HNSCC 11A and
      14C cells and p16-positive CERV196 cells were exposed to different concentrations
      of everolimus, sorafenib and sunitinib for 2-8 days. Expression levels of mTOR
      and AREG were determined by enzyme-linked immunosorbent assay (ELISA) and
      compared against a chemonaive control. RESULTS: AREG and mTOR were expressed in
      all tested cell lines. CERV196 displayed a remarkable increase of mTOR expression
      compared to p16-negative HNSCC. On the contrary, AREG levels were reduced by 50%
      in CERV196. Everolimus, sorafenib and sunitinib significantly reduced mTOR
      expression. Everolimus significantly decreased AREG expression independently of
      the HPV status. Sunitinib and sorafenib increased AREG expression in HNSCC 11A
      and 14C but not in CERV196. CONCLUSION: The applied drugs showed remarkable
      suppression of mTOR expression, which might delay tumor progression.
      Interestingly, sorafenib and sunitinib increased AREG in HNSCC 11A and 14C, which
      could be a possible evasive mechanism following incubation with these drugs. On
      the contrary, p16-positive CERV196 showed increased susceptibility to sorafenib
      and sunitinib concerning suppression of AREG expression. Further studies are
      required to evaluate the HPV-dependent differences of therapy response and the
      possible consequences for treatment options.

PMID- 25862848
TI  - Carbonyl levels and survival rates in oral cancer cells exposed to cigarette
      smoke.
AB  - BACKGROUND: Cigarette smoke (CS) is the main inducer of oral cancer, increasing
      prevalence 4-7 times. MATERIALS AND METHODS: We examined SCC-25 and SCC-15
      suitability for studying CS effects on oral cancer cells, measuring carbonyl
      levels for free radical-mediated CS effect on survival and time/CS dependence.
      RESULTS: Protein oxidation increased significantly during CS exposure. At all
      time points, carbonyl levels increased six-fold (p<0.001) in both cell lines.
      Cell viability decrease was time-dependent. Longer CS exposure led to higher cell
      mortality. At 120 min, SCC-25 cell survival reduction was 43.7%, (p<0.01).
      Propidium iodide (PI) assay results matched the Trypan blue assay showing a time
      dependent cell viability decrease following CS exposure. At 120 min, cell
      survival reduction was 37% (p<0.05). CONCLUSION: Cell death is mediated by CS
      free radicals with pathological process occurring first. Oral cancer cell models
      SCC-25 and SCC-15 are suitable for studying CS-induced free radical-related
      damage, potentially leading to the pathogenesis of oral cancer.

PMID- 25862849
TI  - Sorafenib inhibits migration and invasion of hepatocellular carcinoma cells
      through suppression of matrix metalloproteinase expression.
AB  - Sorafenib increases survival of patients with advanced hepatocellular carcinoma
      (HCC) by inhibiting RAF kinase and receptor tyrosine kinase activity, but
      involvement of sorafenib in fibrosis and epithelial-mesenchymal transition (EMT)
      remains unclear. To elucidate effects of sorafenib on EMT progression and matrix
      metalloproteinase (MMP) activity, levels of E-cadherin, N-cadherin, and MMPs were
      evaluated in HepG2 human HCC cells induced by hepatocyte growth factor (HGF).
      Scratching cell migration assay, matrigel cell invasion assay, and immuno
      histochemistry were performed to examine effects of sorafenib on tumor metastasis
      and MMP expression. Sorafenib inhibited HGF-induced EMT and suppressed cell
      migration and invasion. Treatment with sorafenib significantly reduced HGF
      enhanced expression of MMPs, suggesting that inhibition of MMP activity
      contributes to suppression of cellular motility and invasiveness of HepG2 cells.
      Neutralization of MMP activity by antibodies to MMP2/9, broad-spectrum MMP
      inhibitor or selective gelatinase inhibitor resulted in significant suppression
      of HGF-induced EMT and cell migration/invasion. Sorafenib treatment and MMP
      inactivation inhibited HGF-induced c-MET and MEK/ERK pathways. Sorafenib reduced
      MMP activity in this HGF-induced tumorigenic model of HCC. These findings provide
      in vitro evidence that sorafenib suppresses HGF-induced EMT and cell
      migration/invasion, as well as HGF-induced c-MET and MEK/ERK pathways.

PMID- 25862850
TI  - The therapeutic effect of photon irradiation on viable glioblastoma cells is
      reinforced by hyperbaric oxygen.
AB  - BACKGROUND: Hyperbaric oxygen (HBO) seems to intensify the effect of ionising
      radiation. We investigated whether HBO combined with irradiation decreases the
      capability of U251 glioblastoma cells for relapse and metastasis. MATERIALS AND
      METHODS: Cells were treated with O2 at 1.3 bar and then irradiated with 2 Gy
      photons. Clonogenic survival was tested with colony formation. Motility is an
      important feature of metastasis and was measured with time-lapse videography.
      RESULTS: The clonogenic survival diminished by 22% through HBO, by 49% through
      irradiation, and by 70% through the combination of both. The accumulated distance
      travelled by cells fell by 3% with HBO, rose by 17% with irradiation, but was
      reduced by 11% with their combination. The respective values for the Euclidean
      distance travelled were +8%, +47% and -14%. Compared to normoxic irradiation,
      additional HBO lowered travel by 41%. CONCLUSION: HBO strengthens the effect of
      irradiation on clonogenic survival and reverses radiation-induced increase in the
      mobility of cells.

PMID- 25862851
TI  - Synergistic effect of sorafenib and vitamin K on suppression of hepatocellular
      carcinoma cell migration and metastasis.
AB  - Vitamin K plays a role in controlling cell growth. Anti-angiogenic effects of
      sorafenib lead to impairment of vitamin K uptake and induction of des-gamma
      carboxyprothrombin release by hepatocellular carcinoma (HCC) cells. We examined
      sorafenib and vitamin K individually and in combination regarding their ability
      to suppress migration and metastatic potential of HCC cells. HepG2 cells (HCC
      cell line) were treated with hepatocyte growth factor (HGF). E-Cadherin
      expression, phospho-MET (p-MET), and phospho-extracellular signal-regulated
      kinase (p-ERK) levels and cell migration were evaluated. HGF-stimulated HepG2
      cells, which were treated with a combination of sorafenib and vitamin K, showed
      significantly increased expression of E-cadherin and impairment of migration
      ability compared to when treated with either agent alone. This combination
      therapy also induced marked inhibition of epithelial-mesenchymal transition
      phenotype; inhibition of HGF-stimulated cell proliferation, invasion and
      migration; and inhibition of HGF/c-MET signaling pathway. Levels of p-MET and p
      ERK were also significantly reduced by this combination. Our experimental study
      demonstrated that sorafenib and vitamin K can function synergistically to inhibit
      the migration and proliferation of HCC cells. Combination therapy with sorafenib
      and vitamin K appears to be worthy of clinical trial with expectation of
      synergistic therapeutic effects. 

PMID- 25862852
TI  - The novel CA IX inhibition antibody chKM4927 shows anti-tumor efficacy in vivo.
AB  - Carbonic anhydrase IX (CA IX) is an attractive target for cancer therapy. Many
      anti-CA IX antibodies have been reported but few have been shown to possess
      inhibition activity. Furthermore, effective use of CA IX-inhibition antibodies
      for cancer immunotherapy has not been well-validated since data are mainly
      limited to in vitro assays. In this study, we established that chKM4927, an anti
      CA IX chimeric antibody, recognizes CA IX and has CA IX-specific inhibition
      activity. ChKM4927 also retains antibody-dependent cellular cytotoxicity (ADCC)
      activity against CA IX-expressing cancer cells. Compared to controls, chKM4927
      treatment (10 mg/kg) showed anti-tumor activity in the VMRC-RCW xenograft model
      in vivo. ChKM4927-attenuated ADCC activity showed equally effective anti-tumor
      activity. These results suggest that the CA IX-inhibition antibody chKM4927 has
      an anti-tumor effect in the VMRC-RCW xenograft model via an ADCC-independent
      mechanism. 

PMID- 25862853
TI  - Afatinib is especially effective against non-small cell lung cancer carrying an
      EGFR exon 19 deletion.
AB  - BACKGROUND: A recent pooled analysis of the LUX-LUNG3 and LUX-LUNG6 trials
      suggested that afatinib (an irreversible epidermal growth factor receptor
      tyrosine kinase inhibitor (EGFR-TKI)) is especially effective against non-small
      cell lung cancer (NSCLC) carrying an EGFR exon 19 deletion. MATERIALS AND
      METHODS: Stable viral transfectant HEK293 cell lines carrying an exon 19 deletion
      (HEK293/19 del) or exon 21 L858R mutation (HEK293/ L858R)) were created and their
      drug sensitivities to AG1478 (a reversible EGFR-TKI) and afatinib were examined
      using an MTT assay. Western blot analyses were performed to estimate the
      phosphorylation of EGFR. RESULTS: In the HEK293/19 del, the 50% inhibitory
      concentration (IC50) of afatinib was significantly lower than that in the HEK293/
      L858R. In addition, afatinib inhibited the phosphorylation of EGFR to a greater
      degree in the HEK293/19 del than in the HEK293/L858R. CONCLUSION: Our
      experimental findings suggest that afatinib is especially effective against NSCLC
      carrying an EGFR exon 19 deletion.

PMID- 25862854
TI  - Population stratification effect on cancer susceptibility in an admixed
      population from Brazilian Amazon.
AB  - BACKGROUND/AIM: Many efforts have been made to identify candidate genes involved
      in cancer susceptibility. The present study aimed to investigate the association
      between Arg194Trp (XRCC1), Ala222Val (MTHFR) and Arg521Lys (EGFR) polymorphisms
      (SNPs) and their susceptibility to gastric and breast carcinoma cancer in
      patients from Brazilian Amazon, controlling population structure interference.
      MATERIALS AND METHODS: The SNPs were genotyped by TaqMan(r) SNP Genotyping
      Assays. Ancestry was estimated by analysis of a panel with 48 ancestry
      informative markers. RESULTS: Logistic regression analysis showed an inverse
      association with a 10% increase in African and European ancestry and cancer risk
      (odds ratio (OR)=1.919 and 0.676, respectively). In a preliminary Chi-square
      analysis a positive association between Arg521Lys (EGFR) polymorphism and
      carcinoma susceptibility was found (p=0.037); however, when two different
      methodologies to control population structure bias were utilized, this
      association was lost (p=0.064 and p=0.256). CONCLUSION: Genetic ancestry
      influence gastric and breast cancer risk and highlight the importance of
      population structure inference in association studies in highly admixed
      populations, such as those from Brazilian Amazon.

PMID- 25862855
TI  - Dual expression of shAkt1 and Pdcd4 suppresses lung tumorigenesis in K-rasLA1
      mice.
AB  - BACKGROUND/AIM: Lung cancer has the highest mortality rate among cancers and
      current therapies are not efficient. Therefore, novel therapeutic methods are
      urgently needed. Here, we examined the effectiveness of simultaneous Akt1
      inhibition and Pdcd4 over-expression using a dual expression system in
      suppressing tumorigenesis in K-ras(LA1) mice (a lung cancer model). MATERIALS AND
      METHODS: An shRNA targeting Akt1 (shAkt1) and cDNA of programmed cell death
      protein 4 (Pdcd4) were inserted into a dual expression vector (shAkt1+Pdcd4). A
      sorbitol diacrylate-polyethylenimine (SDA-PEI) carrier was used because of low
      toxicity and high transfection efficiency. Aerosolized SDA-PEI/shAkt1+Pdcd4
      complex was delivered to the mice twice a week for 4 weeks using a nose-only
      exposure inhalation chamber. RESULTS: Simultaneous Akt1 inhibition and Pdcd4 over
      expression synergistically induced potent antitumor effect. Analysis revealed
      significant reduction in lung tumor number. CONCLUSION: Dual expression of shAkt1
      and Pdcd4 effectively suppresses lung tumorigenesis.

PMID- 25862856
TI  - Gene expression analysis for evaluation of potential biomarkers in hepatocellular
      carcinoma.
AB  - BACKGROUND: The poor prognosis of hepatocellular carcinoma (HCC) and the lack of
      specific screening markers underline the need for new biomarkers for human
      hepatocarcinogenesis. MATERIALS AND METHODS: We investigated 10 postulated
      biomarkers for HCC (AFP, GPC3, OPN, IGF1, HGF, SPINK1, KPNA, FUCA1, CgA, HSP90)
      with microarray gene expression analysis and real-time polymerase chain reaction
      (RT-PCR) in HCC tissues of different etiologies. RESULTS: Four candidate genes
      (FUCA1, HGF, IGF1, CgA) showed low median fold changes (fc) of expression
      compared to corresponding non-malignant liver tissues (fc range=0.2-0.8; maximum
      15% of samples). The classic biomarker, alpha-fetoprotein (AFP), was
      significantly over-expressed (fc=2.4) in 30% of tumors. High tumor AFP expression
      was associated with significantly elevated serum AFP concentrations (>90% of
      cases). Five genes (OPN, SPINK1, GPC3, HSP90, KNPA2) showed significantly higher
      expression than AFP in 64% to 82% of samples (median fc range=2.9-8.3). RT-PCR
      analyses gave similar results. CONCLUSION: Unlike previous studies, our results
      did not confirm FUCA1, HGF, IGF1 or CgA as potential markers for HCC. In
      contrast, OPN, SPINK1, GPC3 and KNPA2 were significantly over-expressed in HCC
      tissues. These genes may be useful in developing future biomarkers and
      therapeutic strategies for HCC.

PMID- 25862857
TI  - Search for new genetic biomarkers in poorly differentiated and anaplastic thyroid
      carcinomas using next generation sequencing.
AB  - BACKGROUND: Poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid
      carcinoma (ATC) are very rare tumors with extremely aggressive behavior. Their
      comprehensive genetic background is still unclear. Some of the main genetic
      changes of differentiated thyroid carcinomas, such as mutations in BRAF and RAS
      genes, as well as changes in CTNNB1, PIK3CA, TP53, AXIN1, PTEN or APC genes
      leading to the dedifferentiation of the tumors, are described. MATERIALS AND
      METHODS: DNAs from fresh frozen thyroid tissues of 3 PDTCs and 5 ATCs were
      extracted. The next-generation sequencing (NGS) approach was used to target 94
      genes involved in cancer. The samples were prepared using a TruSight Cancer panel
      and sequenced with a MiSeq sequencer. Analysis of variants was performed by the
      MiSeq Reporter and NextGENe software and stringent criteria for prioritization of
      the variants were used in the Illumina VariantStudio software. RESULTS: Using
      NGS, we identified 26 genetic changes in 18 genes, novel variants included.
      CONCLUSION: NGS is a useful tool for searching for new variants and genes
      involved in PDTC and ATC. It seems that each of these rare tumor types has its
      own specific genetic background. These data could be helpful for recognizing new
      genetic markers and targets for future personalized therapy.

PMID- 25862858
TI  - The role of microRNAs in thyroid carcinomas.
AB  - Thyroid cancers (TCs) are the most common malignancies of endocrine organs. They
      originate from cells of different origin within the thyroid gland, which is
      located at the base of the neck. Several forms of TCs have been classified and
      great variability is observed in molecular, cellular and clinical features. The
      most common forms have favorable prognosis but a number of very aggressive TCs,
      which are characterized by a less differentiated cellular phenotype, have no
      effective treatment at the moment. While TC causes are not completely understood,
      many genetic factors involved in their onset have been discovered. In particular,
      activating mutations of BRAF, RET or RAS genes are known to be specifically
      associated with TC initiation, progression and outcome. The involvement of
      microRNAs in thyroid neoplasms has recently changed the paradigm for biomarker
      discovery in TC, suggesting that these small non-coding RNAs could be used to
      develop, refine or strengthen strategies for diagnosis and management of TCs. In
      this review, the importance of microRNA profiling in TC is explored suggesting
      that these molecules can be included in procedures that can perform better than
      any known clinical index in the identification of adverse outcomes. 

PMID- 25862859
TI  - Effect of perioperative treatment with a hypoxia-inducible factor-1-alpha
      inhibitor in an orthotopic surgical mouse model of thyroid cancer.
AB  - BACKGROUND/AIM: Despite an excellent prognosis, certain patients with thyroid
      cancer suffer from locally invasive disease that cannot be controlled by
      conventional therapy. Our previous study suggested that hypoxia inducible factor
      1-alpha (HIF1alpha) might be an important marker for the identification of and a
      treatment target of intractable thyroid cancer. Therefore, in the present study,
      we established an orthotopic mouse surgical model of thyroid cancer that mimics
      the clinical setting, and evaluated the effect of perioperative treatment with a
      HIF1alpha inhibitor. MATERIALS AND METHODS: Seven thyroid cancer cell lines (SNU
      790, BCPAP, KTC1, TPC1, TPC1-M, KTC2, and FRO) and four HIF1alpha inhibitors
      (echinomycin, LAQ824, temsirolimus, and vorinostat) were used in the present
      study. Expression of HIF1alpha and related proteins was evaluated in all cell
      lines; immunoblotting and cell proliferation assays were conducted; and
      echinomycin was validated in an orthotopic surgical mouse model. RESULTS: Nuclear
      expression of HIF1alpha increased in tumorigenic cell lines, while HIF1alpha
      inhibitors inhibited proliferation and colony formation. In the orthotopic
      surgical model, the group treated with surgery and the echinomycin-treatment
      group showed a highly significant survival gain (p=0.001) compared to the control
      group. CONCLUSION: The highly significant survival gain resulting from their use
      in perioperative adjuvant treatment in vivo and their anticancer effect in vitro
      suggest that HIF1alpha inhibitors might be candidates for perioperative adjuvant
      chemotherapy for thyroid cancer. Combining adjuvant HIF1alpha inhibitor
      chemotherapy with surgery might be an effective therapeutic strategy for thyroid
      cancer that is refractory to conventional treatments.

PMID- 25862860
TI  - Dysregulation of microRNAs in angioimmunoblastic T-cell lymphoma.
AB  - BACKGROUND: Angioimmunoblastic T-cell lymphomas (AITLs) are the second most
      frequent peripheral T-cell lymphomas in humans worldwide and histomorphologically
      well characterized. MicroRNAs are a group of small non-coding RNAs that can
      negatively regulate gene expression on a posttranscriptional level. Their
      dysregulation has been shown to be of importance in numerous tumour entities.
      MATERIALS AND METHODS: As a first step towards understanding the possible
      influence of microRNA-dysregulation in AITL, we analyzed the expression
      signatures of 760 microRNAs in 30 nodal AITLs in comparison to reactive
      lymphadenitis with T-zone hyperplasia. RESULTS: We found miR-34a, miR-146a and
      miR-193b to be up-regulated, as well as miR-140-3p, let-7g, miR-30b and miR-664
      to be down-regulated in AITL to a significant level. CONCLUSION: The microRNA
      signatures of AITL reveal some overlap to autoimmune diseases, virus-triggered
      lymphomas and angiogenic factors that, coupled with future studies, will
      potentially provide better understanding of this disease.

PMID- 25862861
TI  - Structural changes in albumin are a possible mechanism for fluctuation of
      cefazorin and ibuprofen plasma protein binding in rats with carcinogen-induced
      osteosarcoma.
AB  - BACKGROUND/AIM: It is known that the protein-unbound fraction (fp) of warfarin
      fluctuates in the plasma of cancer patients and the fluctuation of fp is
      correlated with albumin concentration. However, this mechanism remains unclear.
      The present study was performed with the objective of elucidating variations in
      the protein-binding rate of specific drugs in the presence of cancer, as well as
      the mechanisms involved. MATERIALS AND METHODS: Experiments were performed using
      Fisher 344 model rats, that we have used in previous studies. A single i.v.
      injection of cefazolin (CEZ) 20 mg/kg or ibuprofen (IB) 10 mg/kg was administered
      to both tumor-bearing and control groups. We compared relevant pharmacokinetics.
      Purified albumin was checked for purity with SDS-PAGE and was used in experiments
      on protein binding of CEZ and IB. RESULTS: The fp of CEZ in plasma from the tumor
      bearing group increased approximately 2.9-fold and the fp of IB also increased
      about 2.7-fold. For that reason, we purified albumin from plasma and examined its
      spectroscopic signature. We showed that conformational changes (i.e., decreases
      in the hydrophobic region, increases in endogenous tryptophan fluorescence
      intensity and decrease in alpha-helical content) had occurred in albumin in the
      tumor-bearing group. CONCLUSION: In the present study, we confirmed that, in a
      state of cancer morbidity, fp was elevated for site I high-affinity CEZ and site
      II high-affinity IB. Moreover, our findings indicated that, as a cause of those
      elevations, a decrease in the albumin concentration and conformational changes
      due to an oxidation are involved.

PMID- 25862862
TI  - The relationship of CD133, histone deacetylase 1 and thrombospondin-1 in gastric
      cancer.
AB  - BACKGROUND/AIM: Gastric cancer is one of the most common types of cancer. Cancer
      stem cells (CSCs) have been reported to play important roles in multiple cancer
      types. This study investigated the correlation between cluster of differentiation
      133 (CD133), histone deacetylase 1 (HDAC1) and thrombospondin-1 (THBS1)
      expression in advanced gastric cancer. MATERIALS AND METHODS: The study included
      65 patients with gastric cancer with recurrence after surgery. Expression of
      CD133, HDAC1 and THBS1 was examined by immunohistochemistry. Prognostic factors
      were investigated by multivariate analysis using Cox's proportional hazard model.
      RESULTS: Clinicopathological variables, including survival, of patients positive
      for CD133 expression (n=6, 23%), were compared with those without CD133
      expression (n=20, 77%). Positive HDAC1 expression and THBS1 expression were
      observed in 34 (52%) and 17 (26%) patients, respectively. Using univariate
      analysis, positive expression of CD133 and negative expression of THBS1 predicted
      significantly worse prognosis. Multivariate analysis revealed CD133-positive and
      THBS1-negative expression were independent prognostic indicators. CONCLUSION:
      CD133 expression and THBS1 expression were prognostic factors, and a negative
      relationship between HDAC and THBS1 was observed in advanced gastric cancer.
      These biomarkers may help determine postoperative treatment in patients with
      gastric cancer.

PMID- 25862863
TI  - Gallic acid induces DNA damage and inhibits DNA repair-associated protein
      expression in human oral cancer SCC-4 cells.
AB  - Gallic acid (GA), a phenolic compound naturally present in plants, used as an
      antioxidant additive in food and in the pharmaceutical industry, may have cancer
      chemopreventive properties. In the present study, we investigated whether GA
      induced DNA damage and affected DNA repair-associated protein expression in human
      oral cancer SCC-4 cells. Flow cytometry assays were used to measure total viable
      cells and results indicated that GA decreased viable cells dose-dependently. The
      comet assay and 4',6-Diamidino-2-phenylindole dihydrochloride (DAPI) staining
      were used to measure DNA damage, as well as condensation and it was shown that GA
      induced DNA damage (comet tail) and DNA condensation in a dose-dependent manner.
      DNA gel electrophoresis was used to examine DNA fragmentation and we found that
      GA induced DNA ladder (fragmentation). Using western blotting it was shown that
      GA inhibited the protein expressions of MDC1, O(6)-methylguanine-DNA
      methyltransferase (MGMT), p-H2A.X, p53, DNA-dependent serine/threonine protein
      kinase (DNA-PK) and 14-3-3 proteins sigma (14-3-3sigma) but increased p-p53,
      phosphate-ataxia-telangiectasia (p-H2A.X) and ataxia telangiectasia mutated and
      Rad3-related (p-ATR), phosphate-ataxia telangiectasia mutated (p-ATM) and breast
      cancer susceptibility protein 1 (BRCA1) in a 24-h treatment. The protein
      translocation was examined by confocal laser microscopy and results indicated
      that GA increased the levels of p-H2A.X, MDC1 and p-p53 in SCC-4 cells. In
      conclusion, we found that GA-induced cell death may proceed through the induced
      DNA damage and suppressed DNA repair-associated protein expression in SCC-4
      cells. 

PMID- 25862864
TI  - Novel in vitro platform to investigate myotube atrophy.
AB  - The electrical current exclusion (ECE) principle provides an alternative to
      common methods of cell diameter measurement and especially in atrophy and cancer
      associated cachexia research. C2C12 myoblasts were differentiated into myotubes
      and treated with 100 MUM dexamethasone to induce atrophy in vitro. Subsequently,
      they were incubated for 24 h with media containing different concentrations of
      curcumin and/or branched-chain amino acids (BCAAs) in order to counteract
      atrophy. After treatment with curcumin, an increase in cell diameter was
      detectable; the highest increase with 13.9 +/- 0.4% was seen with 10 MUM
      curcumin. The combination of curcumin and BCAAs showed an increase of 13.4 +/-
      1.2 %. Cell diameter measurement via the ECE showed that curcumin, and curcumin
      in combination with BCAAs, were able to restore atrophic C2C12 myotubes.
      Therefore, the application of ECE in muscle atrophy and also cancer-associated
      cachexia research allows rapid screening of novel compounds in order to test
      their efficacy in vitro.

PMID- 25862865
TI  - Aberrant glycosylation of alphavbeta3 integrin is associated with melanoma
      progression.
AB  - N-glycosylation of integrins plays an important role in cancer progression.
      Increased alphavbeta3 integrin expression during melanoma progression is well
      documented but the role of its glycans in tumorigenesis is still poorly
      understood. In the present study we used the WM793 primary melanoma cell line and
      its highly metastatic variant, WM1205Lu, to examine alphavbeta3 glycosylation.
      Lectin precipitation, enzyme digestion and the use of swainsonine (SW) showed
      that alphavbeta3 integrin glycosylation differs significantly between primary and
      metastatic melanoma cells. High-mannose structures and complex glycans with
      bisecting N-acetylglucosamine (GlcNAc) were more abundant in both subunits of
      primary cells. We also observed a shift in the sialylation of alphavbeta3
      integrin related to reduction of alpha2-6-linked sialic acid expression and an
      increase of alpha2-3 sialylation of both subunits in melanoma progression.
      Metastatic melanoma migration on vitronectin (VN) was reduced in the presence of
      antibody against alphavbeta3 and the lectins phytohemagglutinin-L (PHA-L),
      Sambucus nigra agglutinin (SNA) and Maackia amurensis (MAA) in woundhealing
      assays. Our results show that the acquisition of metastatic competence by
      melanoma cells is accompanied by alteration of alphavbeta3 integrin glycosylation
      and that both alphavbeta3 and beta1-6-branched sialylated complex-type N-glycans
      promote metastatic melanoma migration on VN. 

PMID- 25862866
TI  - Substituted steroidal compounds containing amino and amido groups reverse
      multidrug resistance of mouse T-lymphoma and two human prostate cancer cell lines
      in vitro.
AB  - BACKGROUND: Resistance to chemotherapy is a main problem in cancer. The search
      for new effective compounds that can increase sensitivity of resistant cells to
      existing chemotherapeutics is an urgent need. In previous studies, it has been
      demonstrated that steroid derivatives showed promising results concerning their
      capacity to modulate resistance of multidrug-resistant cell lines. MATERIALS AND
      METHODS: Steroid derivatives were studied for their growth-inhibitory effect,
      cytotoxicity, reversal of multidrug resistance, apoptosis induction, and
      interaction with doxorubicin on multidrug resistant human ATP-binding cassette,
      sub-family B, member 1 (ABCB1) gene-transfected mouse T-lymphoma cell line, and
      human PC-3 and LNCaP prostate cancer cell lines in vitro. The steroidal
      interaction with P-glycoprotein (ABCB1) was investigated by molecular docking.
      RESULTS: Both the activity of steroid derivatives on inhibition of the ABCB1 pump
      and their interaction with doxorubicin are dependent on the substituent groups of
      the investigated steroidal structures. Even though the investigated steroid
      derivatives were found to have limited antiproliferative effect on the three
      different cancer cell lines, in combination with doxorubicin, most of them acted
      as good potentiators. The binding energies from molecular docking ranged from 
      6.43 to -9.88 kcal/mol. The predicted inhibition constants ranged from 0.1 to
      10.1 MUM. A significant negative correlation was found between binding energy and
      fluorescence activity ratio (R=-0.5, p=0.015). CONCLUSION: The effective
      compounds can be candidates of model molecules for possible application in the
      treatment of multidrug resistant cancer in rational drug design.

PMID- 25862867
TI  - Clinical and prognostic significance of survivin, AKT and VEGF in primary mucosal
      oral melanoma.
AB  - AIM: To investigate survivin, AKT and VEGF expression in primary mucosal oral
      melanoma and explore their correlation with clinicopathological features and
      prognosis. PATIENTS AND METHODS: Twenty malignant primary oral melanomas were
      immunostained with antibodies against survivin, AKT, VEGF, CD34. Histological
      parameters and disease-specific survival were related to marker expressions.
      RESULTS: Survivin localization was both nuclear and cytoplasmic with a higher
      expression of nuclear survivin. High melanocyte survivin expression significantly
      correlated with higher thickness of primary melanoma. A significant positive
      correlation was found between melanocyte survivin and phospho Akt and VEGF
      expression. Survivin was significantly associated with the presence of
      metastasis. High melanocyte survivin and high endothelial VEGF expression were
      inversely correlated to both overall and disease-specific 5-year survival.
      CONCLUSION: Survivin, via AKT and VEGF, seems to play an important role in oral
      melanoma and could represent an important prognostic marker of melanoma
      progression.

PMID- 25862868
TI  - Synchronous quadruple primary neoplasms: glioblastoma, neuroendocrine tumor,
      schwannoma and sessile serrated adenoma in a patient with history of prostate
      cancer.
AB  - Quadruple synchronous primary neoplasms are exceedingly rare with only one case
      reported in the English literature. We herein report a case of synchronous
      quadruple primary neoplasms in a 70-year-old Arabic male with a history of
      prostate cancer who presented to our hospital for work-up of a brain mass found
      at an outside hospital. Subsequent (18)Fluorodeoxyglucose (FDG) positron emission
      tomography demonstrated a 5.9-cm temporoparietal mass and three additional
      lesions, each with increased maximum standardized uptake value (SUV(max)).
      Histologic examination, immunohistochemistry and cytogenetic analyses of the
      lesional tissue revealed four primary neoplastic lesions: primary glioblastoma,
      inguinal schwannoma, well-differentiated neuroendocrine tumor of the terminal
      ileum and an appendiceal sessile serrated adenoma/polyp. This case is unique
      among previous reports as our patient presented with four primary neoplasms
      synchronously. To the best of our knowledge, this combination of synchronous
      multiple primary neoplasms has not been reported in the English literature.

PMID- 25862869
TI  - Extraskeletal osteosarcoma in Norway, between 1975 and 2009, and a brief review
      of the literature.
AB  - AIM: To evaluate the clinicopathological features of extraskeletal osteosarcoma
      (ESOS) and its response to multimodal therapy. PATIENTS AND METHODS: A nationwide
      cohort comprising all Norwegian histologically verified ESOS patients between
      1975 and 2009 supplemented with clinical reports from all hospitals involved in
      sarcoma management. RESULTS: Thirty-seven patients were classified as ESOS,
      mostly elderly people. Seventy-six % had an axial tumour, including nine patients
      with radiation-induced ESOS. The gender balance was equal. The 5-year sarcoma
      specific survival (SSS) was 16 %. Adequate surgical remission had a positive
      impact on SSS, in contrast to chemotherapy and radiotherapy. Primary metastatic
      disease, elevated tumour size and elevated serum alkaline phosphatase, serum
      lactate dehydrogenase and Ki67, respectively, all predicted poor outcome.
      CONCLUSION: The relatively poor prognosis of ESOS may relate to both primary
      chemotherapy resistance and different biologic characteristics of these tumours
      as compared to conventional osteosarcoma. Hence, new predictive molecular markers
      and therapeutic approaches for treatment of ESOS are needed.

PMID- 25862870
TI  - Early effects of adjuvant breast cancer radiotherapy on right ventricular
      systolic and diastolic function.
AB  - AIM: Reduced right ventricular (RV) systolic function correlates with poor
      prognosis in several heart diseases. The aim of this prospective single-Center
      study was to investigate whether conformal three-dimensional (3D) breast cancer
      radiotherapy impairs RV function. PATIENTS AND METHODS: Forty-nine patients with
      early-stage left-sided breast cancer underwent comprehensive two-dimensional (2D)
      echocardiography before and after radiotherapy. RV function was evaluated with
      tricuspid annular plane systolic excursion (TAPSE), pulsed tissue Doppler peak
      velocity at the lateral RV wall (S') and RV and venous flow analysis. RESULTS:
      Radiotherapy reduced TAPSE from 24.5 +/- 4.0 mm to 22.4 +/- 3.9 mm (p<0.001), S'
      from 12.7 +/- 3.1 m/s to 12.2 +/- 2.7 m/s (p=0.11) and pulmonary flow velocity
      time integral (VTI) from 16.6 +/- 3.1 cm to 15.9 +/- 2.3 cm (p=0.07),
      respectively. These changes were unrelated to changes in LV function. CONCLUSION:
      Modern radiotherapy reduced RV systolic function. As a readily-available and
      sensitive measurement, TAPSE is as a practical tool for detection of radiotherapy
      induced cardiac changes.

PMID- 25862871
TI  - Volumetric-modulated arc therapy with vaginal cuff simultaneous integrated boost
      as an alternative to brachytherapy in adjuvant irradiation for endometrial
      cancer: a prospective study.
AB  - AIM: To report preliminary results of a prospective study using pelvic volumetric
      modulated arc therapy and simultaneous integrated boost (SIB-VMAT) on vaginal
      cuff postoperatively in patients with endometrial cancer (EC). PATIENTS AND
      METHODS: Fifty consecutive patients, submitted surgery for EC, were recruited to
      SIB-VMAT prescribing a dose of 54 Gy to the pelvis and 66 Gy to the vaginal cuff
      in 30 fractions. A 2 mm transvaginal probe and magnetic resonance imaging were
      used to define the vaginal cuff. Toxicity data were collected according to Common
      Terminology Criteria for Adverse Events v4.0; clinical outcomes were analyzed.
      RESULTS: The median follow-up was 26 (range=12 to 39) months. According to
      International Federation of Gynecology and Obstetrics 2009, the stages were: IB1
      in 20%, IB2 in 28%, IIA2 in 16%, IIB in 6%, IIIA in 2%, and IIIC in 28%. The 2
      year Overall Survival and Local Control were 96% and 100%, respectively. Two
      pelvic node failures were registered. Acute gastrointestinal toxicity was: G0 in
      12%, G1 in 52%, G2 in 36%; no case of toxicity G3 or more was observed. Acute
      genitourinary toxicity was: G0 in 10%, G1 in 42%, G2 in 48%; no case of toxicity
      G3 or more was observed. No late severe gastrointestinal or genitourinary
      toxicities were reported. A statistical correlation was found between acute G2
      gastrointestinal toxicity with bowel V20 Gy >= 30%, V20 >= 40%, V30 >= 30%, Dmax
      >= 45 Gy. Acute G2 genitourinary toxicity was threefold higher with chemotherapy.
      CONCLUSION: In patients with EC, SIB-VMAT is feasible, and well tolerated.
      Preliminary data of clinical outcome are promising. Further prospective studies
      are advocated.

PMID- 25862872
TI  - Scoring system based on tumor markers and Child-Pugh classification for HCC
      patients who underwent liver resection.
AB  - BACKGROUND: The long-term prognosis of hepatocellular carcinoma (HCC) patients
      after hepatic resection (HR) remains poor because of limited liver function and
      frequent recurrences. We created a prognostic system of HCC based on tumor
      markers and Child-Pugh classification. PATIENTS AND METHODS: This study
      investigated 427 HCC patients and three tumor markers (alpha-fetoprotein (AFP),
      Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), des-gamma 
      carboxyprothrombin (DCP)) in relation to Child-Pugh classification by the
      stepwise Cox regression model for establishing a tumor marker staging (TMS).
      RESULTS: The TMS shows four levels (0/1/2/3) with 5-year recurrence rate of each
      stage of 76.7, 72.3, 80.9 and 100%, respectively, and 5-year overall survival of
      77.0, 68.7, 52.1 and 28.9%, respectively. This TMS appears to be a better model
      to predict the recurrence and survival of HCC patients after hepatectomy than
      only the number of positive tumor markers. CONCLUSION: TMS is a useful staging
      system to evaluate biological status and background liver function.

PMID- 25862873
TI  - Long-term control in a patient with refractory multiple myeloma by oral
      cyclophosphamide and dexamethasone.
AB  - BACKGROUND: Prognosis of patients with multiple myeloma (MM) has substantially
      improved in recent years due to the incorporation of novel drugs into their
      treatment. However, older drugs should be kept in mind when modern drugs have
      failed. CASE REPORT: We report on a 62-year-old female patient with high-risk,
      refractory light-chain myeloma who initially presented with acute renal failure
      and was consecutively treated with six different therapies without achievement of
      sustained disease control. Therapy of cyclophosphamide orally at 50 mg/day (100
      mg twice a week) and dexamethasone at 24 mg once weekly was initiated, resulting
      in a very good partial response which was maintained for more than 21 months. Low
      dose cyclophosphamide in combination with dexamethasone was well-tolerated and no
      significant hematological or nonhematological side-effects were noted.
      CONCLUSION: We suggest that older drugs should be kept in mind as treatment
      options for patients with disease refractory to multiple therapies, including
      novel agents.

PMID- 25862874
TI  - Multiple visceral resection for giant non-secretory adrenocortical carcinoma in
      an elderly patient: a case report.
AB  - Adrenocortical carcinomas are rare tumors in adults. They can be hormonally
      active and detected by a hormonal excess, or be non-secretory tumors. In the
      latter case, they become symptomatic after a long period of growth, usually after
      they have already invaded the surrounding tissues. In these cases, multiple
      visceral resections are sometimes required in order to obtain a complete R0
      resection. We present the case of a 65-year-old patient who was addressed to our
      service for a giant abdominal tumor with compression phenomena in whom we
      performed a complete resection en bloc with left nephrectomy and adrenalectomy,
      distal pancreatectomy, splenectomy, left colectomy and para-aortic lymph node
      dissection. The early postoperative course was uneventful, the patient was
      discharged eight days after surgery. The histopathological findings revealed an
      adrenocortical carcinoma with no lymph node metastases. 

PMID- 25862875
TI  - Post-void residual urinary volume is an independent predictor of biopsy results
      in men at risk for prostate cancer.
AB  - AIM: to determine whether peak flow rate (PFR) and post-void residual urinary
      volume (PVRUV) predict prostate biopsy outcome. PATIENTS AND METHODS: The study
      population consisted of 1780 patients undergoing first prostate biopsy. RESULTS:
      Patients with prostate cancer (PCa) had significantly greater prostate-specific
      antigen (PSA) and PFR but lower prostate volume (PVol) and PVRUV than those
      without PCa. Receiver operator characteristic curve analysis showed that PVol and
      PVRUV were the most accurate predictors of biopsy outcome. The addition of PVRUV
      to the multivariate logistic regression model based on standard clinical
      parameters (age, PSA, digital rectal examination, PVol) significantly increased
      the predictive accuracy of the model in both the population overall (79% vs. 77%;
      p=0.001) and patients with PSA levels up to 10 ng/ml (74.3% vs. 71.7%; p=0.005).
      CONCLUSION: PVRUV seems to be an accurate non-invasive test to predict biopsy
      outcome that can be used alone or in combination with PVol in the decision-making
      process for men potentially facing a prostate biopsy.

PMID- 25862876
TI  - Epirubicin plus paclitaxel regimen as second-line treatment of patients with
      small-cell lung cancer.
AB  - BACKGROUND/AIM: Most patients with small cell lung cancer (SCLC) experience
      relapse within one year after first-line treatment. The aim of this study was to
      describe activity and safety of second-line with epirubicin at 70 mg/m(2)
      followed by paclitaxel at 135 mg/m(2) on day 1 every three weeks for a maximum of
      six cycles. PATIENTS AND METHODS: This is a retrospective review of all patients
      with SCLC evaluated for second-line treatment between 2003 and 2013 at our
      Institution. RESULTS: Sixty-eight patients received the study regimen of
      epirubicin with paclitaxel. We observed partial response in 19 (30%), stable
      disease in 22 (34%) and total early failure rate in 23 (36%) patients. Median
      progression free and overall survival were 21.8 and 26.5 weeks, respectively.
      Haematological toxicities were as follows: grade 3-4 leukopenia and neutropenia
      in 18 (31%) and 30 (22%) of patients, respectively; grade 3 anaemia and grade 4
      thrombocytopenia were reported in 2 (3%) and 5 (9%) of patients, respectively.
      CONCLUSION: Epirubicin with paclitaxel is an active and tolerable second-line
      regimen in patients with SCLC.

PMID- 25862877
TI  - Impact of age on early surgical outcomes of laparoscopy-assisted gastrectomy with
      suprapancreatic nodal dissection for clinical stage I gastric cancer.
AB  - BACKGROUND/AIM: Although laparoscopy-assisted gastrectomy (LAG) is widely used
      for the treatment of gastric cancer, its safety and feasibility for elderly
      patients remains controversial. We herein examined the impact of age on the early
      surgical outcomes of LAG with suprapancreatic nodal dissection for elderly
      patients with clinical stage I gastric cancer. PATIENTS AND METHODS: This
      retrospective study included 292 patients undergoing LAG with suprapancreatic
      nodal dissection for clinical stage I gastric cancer. We divided patients into an
      elderly group (age >= 75 years; n=55) and non-elderly group (age <75 years;
      n=237). Preoperative conditions, operative findings and postoperative outcomes,
      including complications, were compared between these two groups. RESULTS: The
      elderly group had a higher incidence of co-morbidities (61.8%) and lower forced
      expiratory volume in 1 second/forced vital capacity (74.8%). Preoperative levels
      of hemoglobin (Hb) and serum albumin (Alb), as well as the total lymphocyte count
      (TLC) were lower in the elderly group (p<0.001, <0.001 and =0.018, respectively).
      No significant differences were observed in intraoperative findings between the
      two groups. The incidence of overall and surgical complications in the elderly
      group (21.8% and 14.5%, respectively) did not significantly differ from those in
      the non-elderly group. The frequency of non-surgical complications in the elderly
      group (9.1%) was significantly higher (p =0.018), whereas no critical
      complications or mortality were observed. No significant differences were noted
      in the severity of complications or hospital courses between the groups.
      CONCLUSION: LAG with suprapancreatic nodal dissection appears to be safe and
      feasible for elderly patients with clinical stage I gastric cancer.

PMID- 25862878
TI  - Nephroprotective effects of hydration with magnesium in patients with cervical
      cancer receiving cisplatin.
AB  - AIM: The present study aimed to assess the efficacy of 15 mEq magnesium supplied
      as part of a prehydration regimen in preventing cisplatin-induced nephrotoxicity
      in patients undergoing therapy with cisplatin-alone (40 mg/m(2)/week) for
      cervical cancer. PATIENTS AND METHODS: We studied 28 patients with cervical
      cancer. This prospective cohort study compared nephrotoxicity in patients who
      received hydration with and without magnesium sulfate (Mg-hydration group, n=14;
      non-Mg-hydration group, n=14). RESULTS: Baseline characteristics, stage of
      cervical cancer, cisplatin dose and renal function did not differ significantly
      between the two groups. The serum creatinine level significantly increased from
      0.58 to 0.75 mg/dl, and the estimated glomerular filtration rate significantly
      decreased from 85.1 to 66.5 ml/min by chemotherapy in the non-Mg-hydration group.
      In contrast, these levels did not change significantly in the Mg-hydration group.
      CONCLUSION: A magnesium dose of 15 mEq was found to provide nephroprotective
      effects among patients with cervical cancer undergoing chemotherapy with
      cisplatin alone.

PMID- 25862879
TI  - VEGF in patients with advanced hepatocellular carcinoma receiving intra-arterial
      chemotherapy.
AB  - AIM: Vascular endothelial growth factor (VEGF) is a primary driving force for
      both physiological and pathological angiogenesis and over-expression of VEGF has
      been detected in hepatocellular carcinoma (HCC). The aim of the present study was
      to clarify the usefulness of VEGF for monitoring the response to intra-arterial
      chemotherapy in patients with HCC. PATIENTS AND METHODS: Seventy-three patients
      with liver cirrhosis (LC) and advanced HCC (aHCC) received hepatic arterial
      infusion chemotherapy (HAIC: leucovorin (LV) at 12 mg/h, cisplatin (CDDP) at 10
      mg/h and 5-fluorouracil (5-FU) at 250 mg/22 h) via the proper hepatic artery
      every 5 days for 4 weeks using a catheter connected to a subcutaneous drug
      delivery system. RESULTS: i) Serum VEGF levels were higher in patients with
      progressive disease than those in patients with a partial response or stable
      disease. ii) VEGF levels were higher in patients with alcoholic LC than those in
      patients with hepatitis C-related or hepatitis B-related LC. iii) VEGF levels
      were higher in stage IVB patients than those in patients with stage III or IVA
      disease. iv) VEGF levels were significantly higher in patients with giant or
      confluent multinodular tumors than those in patients with multiple discrete
      nodules. v) Serum VEGF levels were higher in patients with vascular invasion than
      in patients without vascular invasion. CONCLUSION: Monitoring the serum VEGF
      level is useful for predicting the response of aHCC to HAIC, as well as for
      predicting metastasis, tumor type and vascular invasion.

PMID- 25862880
TI  - Association of liver steatosis with colorectal cancer and adenoma in patients
      with metabolic syndrome.
AB  - AIM: Metabolic syndrome has been identified as a risk factor for colorectal
      cancer and adenoma. The aim of our study was to assess the risk of colorectal
      cancer and adenoma in an adult Italian population with metabolic syndrome.
      PATIENTS AND METHODS: Ninety patients with metabolic syndrome were prospectively
      compared against a matched population without the syndrome to assess the
      prevalence of colorectal adenoma. Another 1,500 patients undergoing screening
      colonoscopy were prospectively analyzed: 134 patients with metabolic syndrome and
      colorectal adenoma were compared against a group of 108 patients with colorectal
      adenoma without metabolic syndrome to assess the prevalence of cancer. The study
      was performed from January 2008 until December 2010. Data were analyzed from
      March to June 2011. RESULTS: The prevalence of colorectal adenoma was twice as
      high in patients with metabolic syndrome. The incidence of cancer was higher in
      patients with colorectal adenoma and metabolic syndrome. Associated obesity and
      liver steatosis were the only factors with independent statistical value.
      CONCLUSION: Metabolic syndrome is a risk factor for adenoma and cancer
      degeneration when obesity is present. Associated liver steatosis is a significant
      risk factor for colorectal cancer.

PMID- 25862881
TI  - Agreement between hopelessness/helplessness and Montgomery-Asberg Depression
      Rating Scale in healthy individuals and in patients with benign breast disease
      and breast cancer: a prospective case-control study in Finland.
AB  - BACKGROUND: The relation between scoring for hopelessness/helplessness and the
      Montgomery-Asberg Depression Rating Scale (MADRS) in healthy study subjects (HSS)
      and in patients with benign breast disease (BBD) and breast cancer (BC) has not
      been compared in a prospective study. We, therefore, investigated hopelessness
      and helplessness scores versus the MADRS in 115 patients. PATIENTS AND METHODS:
      In the Kuopio Breast Cancer Study, 115 women with breast symptoms were evaluated
      for hopelessness and helplessness, and for the MADRS before any diagnostic
      procedures were carried out. RESULTS: In the self-rating score (SRS),
      hopelessness/helplessness versus the MADRS were highly significantly positively
      correlated in the HSS, BBD and BC groups. In the SRS, the weighted kappa values
      for hopelessness/helplessness versus the MADRS in the HSS, BBD and BC groups were
      also statistically significant. There was also a significant positive correlation
      in the examiner-rating score (ERS) for hopelessness versus the MADRS in the HSS,
      BBD and BC groups and for helplessness versus the MADRS in the HSS, BBD and BC
      groups. The unweighted kappa values in the ERS for hopelessness versus the MADRS
      were statistically highly significant for the HSS, BBD and BC groups and those
      for helplessness versus the MADRS in the HSS and BBD groups were statistically
      significant. CONCLUSION: A new finding with clinical relevance in the present
      work is the agreement between hopelessness/helplessness scores and MADRS in the
      SRS and ERS. In the breast cancer diagnostic unit, the identification of
      hopeless/helpless persons is essential in suicide prevention and it is important
      to assess and treat hopelessness/helplessness even though an individual may
      report few depressive symptoms.

PMID- 25862882
TI  - Preoperative systemic and intraperitoneal chemotherapy consisting of S-1,
      cisplatin and docetaxel in patients with marginally resectable gastric cancer.
AB  - BACKGROUND/AIM: S-1, cisplatin, and docetaxel (DCS) constitute an effective
      regimen for gastric cancer. We conducted a retrospective cohort study of systemic
      DCS and a prospective phase I trial of intraperitoneal DCS in the preoperative
      setting for marginally resectable gastric cancer. PATIENTS AND METHODS: Under the
      systemic regimen, patients received cisplatin (60 mg/m(2)) plus docetaxel (40
      mg/m(2)) intravenously on day 1 and S-1 (80 mg/m(2)) on days 1-14, of a 28-day
      cycle. With the intraperitoneal regimen, the schedule for S-1 and cisplatin was
      the same. Dose escalation for docetaxel started at 30 mg/m(2) (level 1). RESULTS:
      Between August 2010 and July 2013, 26 consecutive patients were treated with the
      systemic regimen. Grade 3-4 neutropenia occurred in 81% but the toxicity profile
      was very tolerable. The response rate based on the Response Evaluation Criteria
      in Solid Tumors (RECIST) was 89%. Between April 2012 and April 2014, 5 patients
      with linitis plastica, large ulcero-invasive type tumors, positive washing
      cytology or peritoneal metastasis were enrolled in the phase I trial of the
      intraperitoneal regimen. Grade 3-4 elevations in aspartate/ alanine
      aminotransferase (AST/ALT) occurred in the first 2 patients. The next 3 patients,
      who received docetaxel (20 mg/m(2)) on days 1 and 15 (level 0), had no dose
      limiting toxicity. Four patients, including 3 with peritoneal metastasis and/or
      positive cytology before treatment, underwent R0 resection after intraperitoneal
      chemotherapy. CONCLUSION: Our studies revealed the efficacy of the systemic
      regimen and the safety of the intraperitoneal regimen. Further investigation of
      these two types of preoperative DCS chemotherapy is warranted.

PMID- 25862883
TI  - Prognostic factors and survival in patients treated surgically for primary and
      recurrent uterine leiomyosarcoma: a single center experience.
AB  - AIM: To (i) determine prognostic factors after initial surgery for uterine
      leiomyosarcomas (LMS) and their recurrence and (ii) assess the effectiveness of
      re-resections. PATIENTS AND METHODS: All cases that underwent surgery for uterine
      leiomyosarcomas at the Fundeni Clinical Institute, Bucharest between 2002 and
      2013 were reviewed. Twenty-six patients with primary uterine leiomyosarcomas were
      introduced in our study. Sixteen of them were re-addressed to the same hospital
      for recurrence. RESULTS: At the moment of initial surgery the most important
      prognostic factors were age <60 years, International Federation of Gynecology and
      Obstetrics (FIGO) stage I, tumor dimension <15 cm and mitotic index <15/10 high
      power fields (HPF). The five-year overall survival was 40%. Sixteen patients were
      re-operated for recurrence; the most important prognostic factors being a late
      recurrence (>12 months) and initial FIGO stage I. The five-year overall survival
      was 12.5%. CONCLUSION: Uterine leiomyosarcoma is an aggressive malignancy with a
      high rate of recurrence. In selected cases surgery may be attempted for re
      recurrence.

PMID- 25862884
TI  - High interleukin-6 mRNA expression is a predictor of relapse in colon cancer.
AB  - AIM: To investigate the expression of interleukin-6 (IL6) in colon cancer tissue,
      and to examine if the risk of relapse is influenced by IL6 expression. MATERIALS
      AND METHODS: Fresh-frozen biopsies from tumor and normal adjacent tissues were
      taken from patients with colon cancer during surgery and stored at -80  degrees
      C. mRNA expression for interleukin-6 was evaluated with reverse transcription
      real time quantitative polymerase chain reaction. Survival analyses were carried
      out using a Cox competing risk regression model. RESULTS: IL6 mRNA was
      significantly more highly expressed in tumor tissue compared to normal adjacent
      tissue (p<0.001). We found no significant association with regard to IL6
      expression and histological differentiation or cancer stage. We found a
      significant association between high IL6 expression and risk of relapse (Hazard
      Ratio=2.23, 95% CI=1.10-4.53; p<0.05), also when adjusted for clinicopathological
      characteristics (Hazard Ratio=2.16, 95% CI=1.07-4.40; p<0.05). CONCLUSION:
      Interleukin-6 is up-regulated in colon cancer tissue at the transcriptional level
      and is significantly associated with increased risk of relapse.

PMID- 25862885
TI  - The role of 18F-FDG accumulation and arterial enhancement as biomarkers in the
      assessment of typing, grading and staging of hepatocellular carcinoma using 18F
      FDG-PET/CT with integrated dual-phase CT angiography.
AB  - AIM: The purpose of the present study was to evaluate the possibility of
      detection, staging and differentiation assessment of hepatocellular carcinoma
      (HCC) using a combination of dual-phase computed tomography (CT)-angiography in
      the arterial and portal phase with positron emission tomography (PET) imaging
      using (18)F-fluorodeoxyglucose ((18)FDG). PATIENTS AND METHODS: From a set of
      10,000 patients who underwent (18)FDG-PET/CT, we examined a total of 65 patients
      (52 males, 13 females; mean age=61.7 years, ranging from 35-82 years) with HCC.
      The imaging included CT data acquisition after intravenous application of
      iodinated contrast material in arterial and portal phases, allowed to obtain data
      in CT angiography quality. Histological diagnosis of the resection sample (21),
      biopsy (37) or necropsy (7), including the evaluation of the hepatocytary origin
      of the tumor and the grade of its differentiation, was determined in all
      patients. RESULTS: The most sensitive sign in the detection of HCC was the
      alternative presence of hypervascularity or hyperaccumulation of (18)F FDG that
      reached 93.8%. The high level of (18)F-FDG accumulation showed sensitivity of
      84.1% and specificity of 75.0% for distinguishing between well- and poorly
      differentiated HCC. CONCLUSION: The combination of the dual-phase CT angiography
      with (18)FDG PET helps in the assessment of staging and differentiation of HCC
      and has an important role in treatment decision-making.

PMID- 25862886
TI  - Efficacy of 18-FDG PET-CT dual-phase scanning for detection of lymph node
      metastasis in gynecological cancer.
AB  - AIM: This study investigated whether dual-phase scanning (DPS) with 18
      fludeoxyglucose positron emission tomography -computed tomography (FDG PET-CT)
      improves diagnosis of lymph node metastasis (LNM) in gynecologic malignancies,
      compared to mono-phase scanning (MPS). PATIENTS AND METHODS: The study included
      139 patients who underwent PET-CT followed by systemic lymph node dissection. PET
      CT scans were obtained twice. The maximum standardized uptake value (SUVmax) was
      measured and the retention index (RI) was calculated as the % change from the
      early to the delayed scan. The optimal threshold of RI was determined using a
      receiver operating characteristic (ROC) curve. Diagnostic efficacies were
      calculated for MPS and DPS using pathological results. RESULTS: In total, 1,879
      regions were dissected. The optimal RI was 9%. The sensitivity, specificity and
      accuracy were 35.8%, 99.0% and 96.8% for MPS and 26.9%, 99.6% and 97.0% for DPS,
      respectively. Specificity was significantly improved by DPS and accuracy was also
      improved, but not significantly. CONCLUSION: DPS had an unsatisfactory impact on
      the diagnostic efficacy for LNM.

PMID- 25862887
TI  - Bevacizumab and postoperative wound complications in patients with liver
      metastases of colorectal cancer.
AB  - AIM: The present study investigated whether bevacizumab (BV) is associated with
      postoperative wound complications (PWCs). PATIENTS AND METHODS: We
      retrospectively analyzed patients undergoing surgery for liver metastases of
      colorectal cancer at our Institution. Patients were divided into 3 groups
      according to the preoperative treatment: che mo therapy with BV (group A),
      chemotherapy without BV (group B) and no chemotherapy (group C). RESULTS: Between
      February 2003 and September 2012, 297 patients underwent 373 surgeries. Groups A,
      B and C consisted of 23, 62 and 288 patients, respectively. PWCs occurred in 29
      patients (7.8%). In multivariate analysis, there were no differences in PWCs
      among the groups (C vs. B:P=0.739; C vs. A: P=0.110). Conversely, lower serum
      albumin levels (<3.5 g/dl vs. >= 3.5 g/dl: p=0.030) and synchronous colorectal
      resection (no vs. yes; p<0.001) remained significant risk factors of developing
      PWCs. CONCLUSION: Chemotherapy with or without BV did not influence the risk of
      PWCs.

PMID- 25862888
TI  - Gastric cancer patients with end-stage renal disease who underwent radical
      gastrectomy.
AB  - BACKGROUND: Radical gastrectomy (RG) with lymph node (LN) dissection is a
      standard procedure for gastric cancer (GC). Patients with end-stage renal disease
      (ESRD) usually have high risk for any operative procedure. However, information
      for ESRD on RG for GC is limited. PATIENTS AND METHODS: A total of 2,021 GC
      patients who underwent RG with LN dissection were retrospectively reviewed. Among
      them, 26 patients had ESRD. The clinicopathological features and surgical
      outcomes were compared between GC with ESRD (ESRD-GC group) and GC without ESRD
      (GC group). RESULTS: ESRD-GC patients could be independently differentiated from
      GC patients by lower hemoglobin, negative lymph node (LN) involvement and higher
      postoperative complications. The overall survival rate of ESRD-GC group seemed
      better than that of GC group patients. Lesser depth of tumor invasion, LN
      metastasis and lymphatic invasion and early-staged tumor contributed to favorable
      prognosis of ESRD-GC group of patients. CONCLUSION: RG might be beneficial for GC
      ESRD patients especially for early-stage disease; however, RG for GC patients
      with ESRD should be more cautiously performed, otherwise the benefit might be
      compromised by higher postoperative complications and even mortality.

PMID- 25862889
TI  - Sorafenib and hepatic arterial infusion chemotherapy for advanced hepatocellular
      carcinoma with portal vein tumor thrombus.
AB  - BACKGROUND: Patients with advanced hepatocellular carcinoma (aHCC) and portal
      vein tumor thrombus (PVTT) still have a very poor prognosis, even though the oral
      multikinase inhibitor sorafenib has revolutionized treatment of aHCC in patients
      with liver cirrhosis (LC). Standardization of multimodal therapy for aHCC with
      PVTT has not yet been achieved. AIM: This retrospective study was performed to
      clarify the usefulness of combined treatment with sorafenib and hepatic arterial
      infusion chemotherapy (HAIC) for patients with LC, aHCC and PVTT. PATIENTS AND
      METHODS: Twenty adult Japanese patients with LC underwent HAIC (HAIC group)
      between 2002 and 2009, while 18 patients received HAIC after treatment with
      sorafenib between 2009 and 2014 (SF-HAIC group). RESULTS: Among patients with
      Child-Pugh class A disease, the median survival time of the SF-HAIC group (315
      days) was significantly longer than that of the HAIC group (197 days), while
      there was no significant difference between the two groups (234 and 228 days)
      among patients with Child-Pugh class B disease. HAIC led to a partial response
      (PR) in 16.7% of patients with class A disease and 21.4% of patients with class B
      disease. With SF-HAIC, PR was obtained in 63.8% and 42.9% of patients
      respectively, although the PR rate was only 9.1% and 0.0%, respectively, after
      treatment with sorafenib alone for four weeks. CONCLUSION: When multimodal
      therapy is employed for patients with LC in Child-Pugh class A disease with aHCC
      and PVTT, performing HAIC after four weeks of sorafenib treatment might improve
      both the tumor response and patient survival.

PMID- 25862890
TI  - Human leukocyte antigen (HLA)-E and HLA-F expression in gastric cancer.
AB  - Human leukocyte antigen (HLA)-E and HLA-F are classified as non-classical HLA
      class Ib antigens. Ectopic HLA-E and HLA-F expression was recently detected in
      cancer cells; however, the clinical implication of their expression remains
      unknown. A total of 209 patients with gastric cancer were enrolled in this study.
      Immunohistochemistry was used to evaluate the expression of HLA-E and HLA-F in
      gastric cancer specimens. HLA-E and HLA-F expression were seen in the cell
      membrane. HLA-E and HLA-F expression significantly correlated with depth of
      invasion, nodal involvement, lymphatic invasion, and venous invasion. No
      significant correlation between HLA-E and HLA-F expression was found (p<0.05,
      r=0.24). The five-year survival rate of the HLA-E-positive group and HLA-F
      positive group were significantly poorer than that of their respective negative
      groups. Combination of HLA-E and HLA-F made the p-value smaller than single
      analysis (p<0.009). This is the first report detailing a clinical implication of
      HLA-E and HLA-F expression simultaneously in gastric cancer. We identified that
      the HLA-E and HLA-F in gastric cancer independently affected clinical factors,
      including postoperative outcome. For HLA-E- or HLA-F-positive gastric cancer, we
      should settle on a treatment strategy that reinforces the host immune response. 

PMID- 25862891
TI  - Clinical significance of CD155 expression in human pancreatic cancer.
AB  - BACKGROUND/AIM: CD155 is expressed in many types of human cells and has diverse
      functions. We herein evaluated the clinical importance of CD155 in pancreatic
      cancer. MATERIALS AND METHODS: We investigated CD155 expression in 134 patients
      with pancreatic cancer, and evaluated the correlations of CD155 with prognosis,
      tumor immunity and angiogenesis. Furthermore, CD155 functions were examined.
      RESULTS: CD155 expression was abundant in pancreatic cancer tissues. Patients
      with high CD155 expression had poorer postoperative prognosis than those with low
      expression. Multivariate analysis indicated that CD155 expression had a
      significant independent prognostic value. Tumor CD155 expression inversely
      correlated with the presence of tumor-infiltrating lymphocytes. Furthermore, it
      significantly positively correlated with vascular endothelial growth factor
      expression and intra tumoral microvessel density. In addition, silencing of CD155
      inhibited proliferation, and induced cell-cycle arrest at G2/M phase in
      pancreatic cancer cells. CONCLUSION: CD155 may play a critical role through both
      immunological and non-immuno logical mechanisms in pancreatic cancer and may be a
      therapeutic target for this intractable malignancy.

PMID- 25862892
TI  - Hyperthermia combined with chemotherapy for patients with residual or recurrent
      oesophageal cancer after definitive chemoradiotherapy.
AB  - BACKGROUND/AIM: Definitive chemoradiotherapy (dCRT) is frequently administered in
      oesophageal cancer. We carried out hyperthermochemotherapy (HCT) for residual or
      recurrent cases after dCRT for oesophageal cancer. The aim of this study was to
      elucidate the usefulness of salvage HCT for these patients. PATIENTS AND METHODS:
      Salvage HCT after dCRT was performed in 11 patients with residual or recurrent
      oesophageal cancer. We used an 8-MHz radiofrequency capacitive heating system for
      hyperthermia. The combined chemotherapy comprised of cisplatin/5-fluorouracil, an
      oral fluoropyrimidine and irinotecan. RESULTS: There were no severe adverse
      events caused by hyperthermia. Complete response and stable disease was achieved
      in three and five patients, respectively; symptoms were improved in the remaining
      three patients. The median survival time after HCT was 12 (range=3-88) months.
      CONCLUSION: HCT is a feasible and potent salvage therapy for patients with
      residual or recurrent oesophageal cancer after dCRT, unless salvage surgery is
      indicated.

PMID- 25862893
TI  - Histopathologic features predictive of aggressiveness of post-transplant
      cutaneous squamous-cell carcinomas.
AB  - BACKGROUND: Squamous cell carcinomas (SCC), the commonest malignancies developing
      in organ-transplant recipients (OTR), may behave aggressively. We searched for
      pathological features of post-transplant SCC that could predict an aggressive
      outcome early. MATERIALS AND METHODS: We pathologically examined 34 SCC developed
      in OTR that developed later recurrences/metastases, and compared them with 25 non
      aggressive SCC excised from the same OTRs over the same period of time for
      features believed to predict an aggressive outcome (tumour size and thickness,
      ulceration, deep tissue invasion, mitotic rate, differentiation, peritumoural
      infiltrate density, acantholysis, perineural and lymphovascular invasion).
      RESULTS: A statistically significant difference was found for the level of tumour
      invasion (Clark), as 58% (18/34) of aggressive SCCs (vs 24% (6/25) of non
      aggressive SCCs) were of levels IV or V. CONCLUSION: Post-transplant SCCs with a
      Clark level of IV or V are associated with a higher risk for recurrence and
      metastasis and call for a close patient follow-up.

PMID- 25862894
TI  - Low-dose pressurized intraperitoneal aerosol chemotherapy (PIPAC) as an
      alternative therapy for ovarian cancer in an octogenarian patient.
AB  - BACKGROUND: Octogenarians with ovarian cancer limited to the abdomen may not be
      willing or able to undergo systemic chemotherapy. Low-dose pressurized
      intraperitoneal aerosol chemotherapy (PIPAC) with cisplatin and doxorubicin is a
      form of intra-abdominal chemotherapy which can be applied repeatedly and
      potentially prevents from the systemic side-effects of chemotherapy. CASE REPORT:
      We present the case of an 84-year-old woman with laparoscopically and
      histologically confirmed ovarian cancer who refused to undergo systemic
      chemotherapy. She was treated with eight courses q 28-104 days of low-dose PIPAC
      with cisplatin at 7.5 mg/m(2) and doxorubicin at 1.5 mg/m(2) at 12 mmHg and 37 
      degrees C for 30 min. Objective tumor response was noted, defined as tumor
      regression on histology, and stable disease noted by peritoneal carcinomatosis
      index on repeated video-laparoscopy and abdominal computed tomographic scan. The
      treatment was well-tolerated with no Common Terminology Criteria for Adverse
      Events (CTCAE) CTCAE >2. With a follow-up of 15 months, the patient is alive and
      clinically stable. The quality of life measured by the European Organisation for
      Research and Treatment of Cancer (EORTC) QLQ-C30 demonstrated improvement over 5
      6 months (global physical score, global health score, global quality of live)
      without cumulative increase of gastrointestinal toxicity. CONCLUSION: Low-dose
      PIPAC is a new form of intraperitoneal chemotherapy which may be applied
      repeatedly in octogenarian patients. PIPAC may be an alternative and well
      tolerated treatment for selected octogenarian patients with ovarian cancer
      limited to the abdomen who cannot be treated with systemic chemotherapy.

PMID- 25862895
TI  - Initial incomplete surgery modifies prognosis in advanced ovarian cancer
      regardless of subsequent management.
AB  - BACKGROUND: Prognosis in ovarian cancer is determined by completeness of
      cytoreduction and proper management by specialized oncological gynecologists.
      Incomplete initial debulking surgery in non-specialized Centers is, however, a
      reality and there is ongoing discussion about the best subsequent management of
      such patients. PATIENTS AND METHODS: Patients with advanced ovarian cancer
      (International Federation of Gynecology and Obstetrics--FIGO FIGO stages IIIC-IV)
      who had biopsy by laparotomy or incomplete cytoreduction followed or not by
      chemotherapy further referred to our Institution between January 2002 and May
      2014 were included. The two groups of incomplete cytoreduction [followed by
      upfront surgery or followed by chemotherapy and interval debulking surgery (IDS)]
      were compared and also compared against a cohort of 197 patients with similar
      characteristics who underwent upfront maximal surgery according to the standard
      at our Iinstitution during the same period. RESULTS: A total of 99 eligible
      patients were identified. Sixty-seven of them underwent biopsies by laparotomy
      and 32 underwent incomplete cytoreduction in other institutions. Twenty-eight
      patients underwent direct re-operation while 71 patients underwent neoadjuvant
      chemotherapy followed by IDS. The mean overall survival duration for patients
      with upfront reoperation was 31 months and 54 months for patients with
      neoadjuvant chemotherapy and IDS, considerably lower than the 72 months obtained
      for the group of 197 patients with maximal up-front complete cytoreduction at our
      Institution. CONCLUSION: Primary biopsy or incomplete cytoreduction reduces
      survival regardless of the subsequent approach. However, if incomplete
      cytoreduction has occurred, neoadjuvant chemotherapy followed by IDS is
      preferable to up-front reoperation.

PMID- 25862896
TI  - Expression of phosphorylated Akt, mTOR and MAPK in type I endometrial carcinoma:
      clinical significance.
AB  - BACKGROUND/AIM: The Akt/mTOR and MAPK pathways are frequently activated in
      various tumor types but data on endometrial carcinoma are limited. The aim of the
      present study was to investigate the clinical significance of the expression of
      phosphorylated MAPK, Akt and mTOR (p-MAPK, p-Akt, p-mTOR) in type I endometrial
      carcinoma. MATERIALS AND METHODS: The study comprised of 103 formalin-fixed
      paraffin-embedded (FFPE) type I endometrial carcino ma cases, retrospectively
      retrieved and assessed by immuno histochemistry for p-MAPK, p-Akt and p-mTOR
      expression. The expression of these proteins was also studied in non-neoplastic
      endometrial tissue adjacent to the tumor. RESULTS: The expression patterns of
      these molecules differed between malignant and non-tumorous tissue specimens. The
      immuno reactivity for p-Akt was exclusively detected in the neoplastic tissues.
      Expression levels of p-MAPK were higher in tumors compared to non-neoplastic
      endometrium (p<0.001), while p-mTOR was found to be over-expressed in non-neo
      plastic endometrium compared to carcinomas (p=0.001). Expression of p-Akt was
      correlated with p-MAPK protein levels (p=0.022, r=0.229). On the other hand, no
      association was found with clinicopathological parameters and with disease-free
      (DFS) or overall survival (OS) of the patients. CONCLUSION: Our findings support
      the de-regulation of the PI3K/Akt/mTOR and MAPK signaling pathways in type I
      endometrial carcinomas suggesting involvement of these pivotal pathways in
      endometrial carcinogenesis.

PMID- 25862897
TI  - Risk of anemia attributable to everolimus in patients with cancer: a meta
      analysis of randomized controlled trials.
AB  - BACKGROUND: Everolimus, an inhibitor of mammalian target of rapamycin (mTOR) used
      for the treatment of various solid tumors, is associated with anemia, which can
      lead to morbidity and treatment interruption or discontinuation. Because the
      underlying causes of anemia can be multifactorial, we performed a meta-analysis
      of randomized controlled trials (RCTs) to determine the overall risk of anemia
      specifically attributable to everolimus in cancer patients. MATERIALS AND
      METHODS: We searched the PubMed database and abstracts presented at the American
      Society of Clinical Oncology annual meetings up to May 2014 for relevant studies.
      Eligible studies included RCTs in which everolimus alone or in combination with
      other agents was compared to placebo alone or with other agents in patients with
      cancer. Summary incidences, relative risks (RR), and 95% confidence intervals
      (CI) were calculated using a random- or fixed-effects model depending on the
      heterogeneity of the included trials. The attributable risk was determined by the
      incidence with everolimus minus that without everolimus in controls. RESULTS: A
      total of nine RCTs with 3,678 patients (everolimus, n=2,162; controls, n=1,516)
      were included in our analysis. In comparison with controls, everolimus
      significantly increased the risk of all-grade (RR=2.18, 95% CI=1.56-3.04,
      p<0.001) and high-grade anemia (RR=2.63, 95% CI=1.35-5.15, p<0.001). The summary
      incidences of all-grade (grades 1-4) and high-grade (grades 3-4) anemia in
      patients treated with everolimus were 32.1% (95% CI=17.5-51.3%) and 6.9% (95%
      CI=4.1-11.3%) respectively, with 13.3% (95% CI=10.0-17.5%) and 4.7% (95% CI=2.8
      7.7%) specifically attributable to everolimus. Risk factors of high-grade anemia
      attributable to everolimus included tumor type (p=0.012), with the highest seen
      in renal cell carcinoma (8.0%, 95% CI=5.3-11.9%), and chemotherapy (p<0.001).
      CONCLUSION: There is a substantial risk of all-grade and high-grade anemia
      attributable to everolimus therapy for cancer.

PMID- 25862898
TI  - Necessity for resection of gastric gastrointestinal stromal tumors <= 20 mm.
AB  - BACKGROUND/AIM: To evaluate whether surgical intervention was useful in patients
      undergoing surgery for gastric gastrointestinal stromal tumors (GISTs), for
      tumors <= 20 mm in size. PATIENTS AND METHODS: Between August 2002 and July 2014,
      138 patients with GIST underwent surgery at our Hospital, including 112 patients
      with gastric GISTs. The medical records of these patients were retrospectively
      reviewed. RESULTS: Postoperative recurrence was observed in three patients, each
      having tumors with high mitotic rates and >= 21 mm in size. In 89 patients
      undergoing gastric wedge resection, the incidence of postoperative complications
      was 10.1%; 5.6% of the patients developed late sequelae, all of which were mild.
      The group classified as having tumors >= 21 mm in size had a higher proportion of
      elderly patients (p=0.0010), more complications (p=0.0152), and longer hospital
      stay (p=0.0589). CONCLUSION: To prevent recurrence, definitive diagnosis and
      aggressive resection while the tumor size is 20 mm or less is recommended.
      However, because some patients also carry surgical risks, sufficient
      consideration must be given to the needs of individual patients.

PMID- 25862899
TI  - BRAF V600E mutation in colorectal cancer is associated with right-sided tumours
      and iron deficiency anaemia.
AB  - BACKGROUND: BRAF gene encodes a serinethreonine kinase that inhibits the RAS/MAPK
      intracellular pathway. BRAF mutations occur at an early stage of colorectal
      cancer and their presence, 10-20% of colorectal cancer (CRC), is usually
      associated with inferior prognosis. MATERIALS AND METHODS: From 41 consecutive
      CRC confirmed referrals from 1,446 suspected cancer cases (mean age=67.99+13.451,
      male=21, female=20), we retrospectively analyzed collected data from haemoglobin
      (Hb) and symptoms at presentation, location of tumor and stage of the disease,
      including lymphovascular invasion (LVI). Gene profile analysis data (KRAS, BRAF)
      were retrospectively collected and associated with the presentation profile
      above. RESULTS: There was no significant correlation in presentation Hb levels
      and eventual disease staging (p>0.05 for all associations). Patients with right
      sided tumours were found to have a lower Hb level than patients with either left
      sided colonic or rectal tumours. Hb levels were also significantly lower in
      patients with the BRAF V600E mutation. KRAS status or LVI status did not have a
      specific correlation with Hb levels. CONCLUSION: BRAF V600E mutation might be
      associated with right-sided tumors and subsequently related unexplained iron
      deficiency anaemia (IDA) at presentation. This finding may affect the choice of
      clinical strategy for investigation of unexplained IDA. Further research should
      be conducted in order to identify and support the potential biological
      explanation of the findings above.

PMID- 25862900
TI  - Diffusion-weighted imaging using 3.0 T MRI as a possible biomarker of renal
      tumors.
AB  - BACKGROUND/AIM: Diffusion-weighted imaging (DWI) allows for differentiation of
      benign from malignant tumors, histological tumor types and their grade. The aim
      of the study was to evaluate the capabilities of DWI using 3 Tesla Magnetic
      resonance imaging (3T MRI) in the preoperative assessment of renal tumors.
      PATIENTS AND METHODS: This retrospective study included 143 tumors in 139
      patients (130 malignant tumors and 13 benign tumors) that were examined using DWI
      with b values of 50, 400 and 800 s/mm(2). In all tumors, the lowest value of
      apparent diffusion coefficient (ADC) in the solid tissue was measured and
      correlated with the histological finding. RESULTS: A significant difference
      between ADCs of malignant and benign tumors was found (p<0.001). Comparison of
      the most common malignant and benign tumors clear-cell renal carcinoma (CCRCC)
      grade I and oncocytoma resulted in a difference of borderline significance with a
      marked overlap (p=0.046). By assessing the histological types of malignant
      tumors, we detected a significant difference between CCRCC and all other
      histological types (p=0.048 for chromophobe (CH) RCC, p=0.002 for papillary (P)
      RCC and p=0.002 for urothelial carcinoma (UC)). Mutual differentiation of other
      types of carcinomas was not feasible (p=1.0 in all cases). The differences
      between low-grade (grade I+II) and high-grade (grade III+IV) CCRCC was
      significant (p<0.001). A significant difference was found even between CCRCC
      grade I and others (p=0.01 for grade II, p<0.001 for grade III+IV, respectively).
      CONCLUSION: DWI may contribute in distinguishing CCRCC from other histological
      types and to determinits grade. The method has certain potential for
      distinguishing benign from malignant tumors; however, differentiation of the most
      frequently represented types, CCRCC grade I and oncocytoma, remains difficult.

PMID- 25862901
TI  - Post-chemotherapeutic CEA and CA19-9 are prognostic factors in patients with
      colorectal liver metastases treated with hepatic resection after oxaliplatin
      based chemotherapy.
AB  - BACKGROUND/AIM: The prognostic value of tumor markers remains unclear in patients
      with colorectal liver metastases (CRLM) who undergo hepatectomy following
      chemotherapy. The aim of the present study was to identify prognostic factors
      associated with recurrence and survival in such patients. PATIENTS AND METHODS:
      Between 2005 and 2012, 62 patients with initially unresectable or marginally
      unresectable CRLM who underwent hepatectomy following chemotherapy were enrolled.
      A Cox proportional hazards model was used to identify the prognostic factors.
      RESULTS: Multivariate analysis indicated that a high level of carbohydrate
      antigen 19-9 (CA19-9) in serum post-chemotherapy was significant factor,
      predictive of poor overall survival [Hazard Ratio (HR)=4.46, 95% Confidence
      Interval (CI)=1.68-11.8; p=0.003] and marginally significant regarding poorer
      relapse-free survival (HR=2.11, 95% CI=0.99-4.47; p=0.050). Non-response to
      preoperative chemotherapy was a significant prognostic factor regarding shorter
      relapse-free (HR=2.18, 95% CI=1.10-4.33; p=0.026) and overall survival (HR=3.14,
      95% CI=1.22-8.08; p=0.018). High levels of carcinoembryonic antigen CEA in serum
      post-chemotherapy (HR=3.08, 95% CI=1.13-8.39; p=0.028) and the absence of
      adjuvant chemotherapy (HR=2.27, 95% CI=1.17-4.41; p=0.016) were independent risk
      factors for recurrence. CONCLUSION: Measurement of both CEA and CA19-9 level is
      strongly recommended for patients with CRLM treated with preoperative
      chemotherapy followed by hepatectomy because normalization of serum CEA and CA19
      9 levels after chemotherapy will demonstrate a good prognosis after curative
      hepatectomy.

PMID- 25862902
TI  - Clinical decision-making in atypical and suspicious categories in fine-needle
      aspiration cytology of the breast.
AB  - BACKGROUND: Fine-needle aspiration cytology (FNAC) is a simple and reliable
      technique to assess breast lesions, although a definitive differential diagnosis
      (benignity vs. cancer) is achieved approximately in 60-70% of cases because an
      inadequate (C1), atypical (C3) or suspicious (C4) category is otherwise reported.
      PATIENTS AND METHODS: A retrospective analysis of 763 cases with C3 or C4 reports
      was performed to define their positive predictive value (PPV), as well as the
      practical implications of clinical and imaging findings as for clinical decision
      making. FNACs were collected from January 2003 to September 2012 at the Breast
      Unit of IRCCS "A.O.U. San Martino-IST" Genoa, with each being received later to
      definitive histology. The PPV for cancer of C3/C4 categories were computed to
      measure the accuracy of FNAC; moreover, the PPV was also stratified according to
      clinical, mammography and sonography data alone or by their combination. RESULTS:
      The PPV of C3 and C4 was 21.1% (80/380) and 84.1 % (322/383), respectively.
      Within each C3/C4 category, a significant direct correlation (p<0.001) between
      the suspicion index of clinical, mammography and sonography data and cancer
      detection rate was always observed. The PPV of C3/C4 stratified by the
      combination of clinical and imaging findings showed satisfactory values in the C3
      category only when there was an agreement between clinical and imaging findings,
      whereas the PPV of the C4 category was always remarkably high (ranging from 92.3%
      to 100%). CONCLUSION: the diagnostic work-up in C4 reports or in patients with a
      C3 report but with an high suspicion index at clinical or imaging examination
      should be preferably implemented by means of a core biopsy to optimize the
      therapeutic planning; given a C3 report with dubious clinical and/or imaging
      findings, an excisional biopsy (or in alternative vacuum-assisted breast biopsy
      with complete removal of the nodule) should be preferably performed in order to
      reach a definitive histological dia gnosis with no further delay.

PMID- 25862903
TI  - Analysis of the risk factors for febrile neutropenia in patients with bone and
      soft tissue sarcoma.
AB  - BACKGROUND: Although systemic chemotherapy is inevitably selected as the modality
      of treatment for high-grade bone and soft tissue sarcoma (BSTS), limited
      information is available regarding febrile neutropenia (FN). PATIENTS AND
      METHODS: FN incidence, blood culture results and risk factors were analyzed in 35
      patients with high-grade BSTS. RESULTS: FN occurred in 51% of the patients and
      24% of the courses of systemic chemotherapy. Culture results indicated pathogen
      in only 33.3% of patients who had FN. Methicillin-resistant Staphylococcus
      epidermidis and methicillin-resistant Staphylococcus aureus were frequently
      observed. Body weight of less than 61.0 kg and a tumor originating from the bone
      in a patient-based analysis, and serum albumin <4.2 g/dl and having a source of
      infection in a course-based analysis were independent risk factors for FN.
      CONCLUSION: Considerably high risks for FN during chemotherapy for BSTS were
      confirmed. The risk factors presented here appeared to differ from those in
      previously reported guidelines.

PMID- 25862904
TI  - Critical evaluation of a prospective study of concurrent chemoradiotherapy with S
      1 for early glottic carcinoma.
AB  - AIM: To improve the outcomes of radiotherapy alone for T2 glottic carcinoma (GC),
      we initiated a prospective study of concurrent chemoradiotherapy with S-1 for
      patients with early GC, primarily T2 cases. We report the efficacy and safety of
      this protocol. PATIENTS AND METHODS: Eligible patients had T1b or T2 glottic
      squamous cell carcinomas. Patients received S-1 (55.3 mg/m(2)/day, once daily)
      and radiotherapy (2 Gy/day, five days/week, to a total of 30 fractions). RESULTS:
      Thirteen patients were eligible. Complete responses were observed in all 13
      patients (100%). At a median follow-up duration of 53 months (range=23-68
      months), the 3-year local control and overall survival rates were both 100%.
      Grade 3 dermatitis occurred in only one patient. CONCLUSION: This
      chemoradiotherapy protocol is well -tolerated and effective in patients with
      early glottic carcinoma. Furthermore, due to its once-daily administration, this
      protocol is considered to be easier than usual chemoradiotherapy, and makes
      outpatient-treatment possible.

PMID- 25862905
TI  - Bevacizumab and first-line chemotherapy for older patients with advanced
      colorectal cancer: final results of a Community-based Observational Italian
      Study.
AB  - BACKGROUND: Although the efficacy and safety of combining first-line chemotherapy
      with bevacizumab in elderly patients with colorectal cancer (CRC) is supported by
      the results of a phase III trial, real-practice data are limited. PATIENTS AND
      METHODS: Our multi-center, community-based observational study included 233
      elderly patients with CRC (median age=73 years, range=70-84 years). Baseline
      comorbidities and geriatric evaluation were also analyzed. Pre-specified end
      points of the study were safety, tolerability and outcome results. RESULTS: The
      incidence of both chemotherapy-induced and specific bevacizumab-related
      toxicities was low, and not influenced by baseline concurrent morbidities. Median
      progression free survival (PFS) and median overall survival (OS) were 9.9 months
      and 23.6 months, respectively. Fifty-six percent of patients received second-line
      chemotherapy. CONCLUSION: The upfront treatment of older patients with CRC with
      chemotherapy and bevacizumab is safe and efficacious in a real-world setting. No
      un expected toxicities were reported. Multi-dimensional geriatric evaluation is
      under-used in clinical practice.

PMID- 25862906
TI  - Impact of postoperative complications on survival and recurrence in pancreatic
      cancer.
AB  - BACKGROUND: We investigated the impact of postoperative complications on survival
      and recurrence after curative surgery for pancreatic cancer. PATIENTS AND
      METHODS: This study included 164 patients who underwent curative surgery for
      pancreatic cancer between 2005 and 2014. The patients were classified into those
      with postoperative complications (C group) and those without postoperative
      complications (NC group). The risk factors for overall survival (OS) and
      recurrence-free survival (RFS) were identified. RESULTS: Postoperative
      complications were found in 61 out of the 164 patients (37.2%). The RFS rate at
      five years after surgery was 10.6% in the C group and 21.0% in the NC group. The
      RFS tended to be worse in the C group than in the NC group (p=0.1756). The OS
      rate at five years after surgery was 7.4% in the C group and 22.8% in the NC
      group, which was significantly different (p=0.0189). The multivariate analysis
      demonstrated that the occurrence of postoperative complications was a significant
      independent risk factor for OS and a marginally significant risk factor for RFS.
      CONCLUSION: The development of postoperative complications was a risk factor for
      a decreased overall survival in the patients who underwent curative surgery for
      pancreatic cancer. The surgical procedure, perioperative care and the surgical
      strategy should be carefully planned to avoid complications.

PMID- 25862907
TI  - Src kinase-associated phosphoprotein2 expression is associated with poor
      prognosis in non-small cell lung cancer.
AB  - BACKGROUND/AIM: Non-small cell lung cancer (NSCLC) is among the leading causes of
      cancer-related deaths worldwide. In certain human cancer types, Src is associated
      with cancer progression and refractory cancer. To improve the prognoses of NSCLC
      patients, we evaluated Src kinase-associated phosphoprotein 2 (SKAP2), a factor
      associated with integrin-stimulated cytoskeletal rearrangement, as a new
      therapeutic target. MATERIALS AND METHODS: We performed immunohistochemistry for
      SKAP2 in 99 NSCLC samples and evaluated the relationship between SKAP2
      expression, clinicopathological factors and prognosis. RESULTS: Higher SKAP2
      expression was detected in cancerous tissues and was predominantly expressed in
      the cytoplasm. Elevated SKAP2 expression levels were associated with poor
      prognosis (p=0.007) and shorter survival time after recurrence (p=0.035). High
      SKAP2 expression was an independent prognostic factor in NSCLC patients
      (p=0.027). CONCLUSION: High SKAP2 expression levels in NSCLC tissues could be a
      powerful biomarker of poor prognosis. Therefore, SKAP2 is a promising candidate
      molecular target for NSCLC treatment.

PMID- 25862908
TI  - Pathological patterns of prostate biopsy in men with fluctuations of prostate
      cancer gene 3 score: a preliminary report.
AB  - BACKGROUND: To evaluate pathological patterns of prostate biopsy in men with
      changes in risk class by prostate cancer gene 3 (PCA3) score and with elevated
      serum prostate-specific antigen (PSA) or positive digital rectal examination
      (DRE), undergoing a repeat biopsy. PATIENTS AND METHODS: A total of 108 males of
      two Italian Institutions who had undergone at least two PCA3 score assessments
      with changed PCA3 risk class were selected. Comparison of PCA3 score in patients
      with negative re-biopsy [normal parenchyma, benign prostatic hyperplasia (BPH),
      chronic prostatitis, high-grade prostate intraepithelial neoplasia (HG-PIN),
      atypical small acinar prostate (ASAP)] or positive re-biopsy was performed.
      RESULTS: The up- and down-grading rates for PCA3 score were 71.3% (n=77) and
      28.7% (n=31), respectively. Among the 77 up-graded patients, the median change in
      PCA3 score was 24 (range=4-69), while among the 31 down-graded ones, the median
      change was 17 (2 to 55). The PCA3 score in 24 out of 29 (82.7%) patients with
      prostate cancer (PCa) was up-graded. No association was found for correlation of
      PCA3 score change with age >65 years (p=0.975), family history of prostate cancer
      (p=0.796), positive DRE (p=0.179), use of 5-alpha-reductase inhibitors (p=0.793)
      and BPH/prostatitis/HG-PIN/ASAP diagnosis (p=0.428). CONCLUSION: PCA3 score can
      be considered a marker that is stable over time in most cases; notably, up to 20%
      of patients have a clinically relevant change of risk class. The rate of PCa was
      higher in patients whose PCA3 score was up-graded, even if no robust cut-off for
      PCA3 score fluctuation was identified.

PMID- 25862909
TI  - miR-7 expression in serous ovarian carcinomas.
AB  - BACKGROUND/AIM: miR-7 has recently been linked to cancer. Some miR-7 targets,
      including B-cell lymphoma 2 (BCL2) and epidermal growth factor receptor (EGFR),
      are involved in ovarian cancer (OC) pathogenesis. The majority of OCs display
      TP53 mutations, which are critically important for OC development. We aimed to
      study the expression level of miR-7 and of two of its postulated target genes,
      BCL2 and EGFR, in serous ovarian carcinomas of different TP53 status and tumour
      grade. MATERIALS AND METHODS: Gene and miR expression was assessed by real-time
      reverse transcription polymerase chain reaction in 45 clinical samples of low-
      (G1+G2) and high- (G3) grade primary serous OC with wild-type (wt) or mutated
      TP53, as well as in three OC cell lines, each representing a different TP53
      status. The results obtained in patients with OC were analysed against their
      disease-free survival (DFS). RESULTS: In high-grade OC with TP53 mutations, the
      level of miR-7 expression significantly exceeded (by several fold) that in wtTP53
      cancer (p<0.01). Within the wtTP53 tumour series, the level of miR-7 expression
      was significantly higher (by over 10-fold) in high-grade than in low-grade OC
      (p<0.01). miR-7 expression was not found to influence DFS. The differences in miR
      7 expression depending on TP53 status found in clinical OC samples were not
      observed in OC cell lines. miR-7 overexpression correlated with diminished BCL2
      expression, but there was no relationship between miR-7 and EGFR expression,
      neither in tumour samples nor in the cell lines. CONCLUSION: There is a link
      between miR-7 expression and TP53 status and tumour grade in serous OC. Molecular
      mechanisms of these relationships need to be elucidated. Of the two postulated
      miR-7 target genes we examined, BCL2, but not EGFR, seems to be a possible miR-7
      target in OC.

PMID- 25862910
TI  - Radiation-induced second malignancies.
AB  - BACKGROUND: The number of patients with second malignancies is growing and they
      represent about one in six out of all new cancers. Second malignancies can be
      categorized into three major groups according to the predominant etiological
      factor(s): (i) treatment-related, (ii) part of a syndrome and (iii) those due to
      shared etiologic exposures. PATIENTS AND METHODS: This article focuses on
      radiation-induced malignancies with illustrative cases of thyroid, rectal cancer
      and sarcoma. RESULTS: The detection and management of radiation-induced
      malignancies of some case scenarios are presented. Second malignancies are
      detected within previous radiation field and the time intervals from previous
      tumor vary from 8 to 21 years. CONCLUSION: Clinicians should aim to reduce
      radiation-induced malignancies by careful selection of patients and radiation
      techniques before radiotherapy. Subsequent vigilant follow-up and investigations
      can detect these radiation-induced malignancies early and, hence, result in
      successful treatment.

PMID- 25862911
TI  - Assessment of circulating serum DNA integrity in colorectal cancer patients.
AB  - Background /Aim: Studies evaluating the integrity of cell-fee DNA (cfDNA) in
      colorectal cancer (CRC) have led to inconsistent results. Herein, we analyzed the
      utility of two different DNA integrity indexes (ACTB(384)/ACTB(106) and
      ALU(247)/ALU(115)) to assess cfDNA fragmentation in Turkish CRC patients. The
      correlation of circulating nucleosomes (cNUC) with the fragment sizes was also
      evaluated. MATERIALS AND METHODS: Seventy two CRC patients and 42 CRC-free
      control individuals were enrolled in the study. cfDNA was analyzed by
      quantitative polymerase chain reaction (qPCR). RESULTS: While with
      ALU(247)/ALU(115)there was a small difference between the groups, an
      approximately 3-fold (median values=0.12 and 0.34) lower integrity was found in
      the patients using the ACTB(384)/ACTB(106) ratio (p=0.06). The correlation
      between cNUC and qPCR threshold cycles was much higher for shorter fragments.
      CONCLUSION: Lower DNA integrity and the predominance of mononuclesomes in serum
      reveal high fragmentation of cfDNA in CRC patients.

PMID- 25862912
TI  - Correlation of HER2 expression with clinicopathological characteristics and
      prognosis in resectable gastric cancer.
AB  - Results from the Trastuzumab for Gastric Cancer (ToGA) trial highlighted the
      clinical significance of trastuzumab in the treatment of HER2 (Human Epidermal
      Growth Factor Receptor type 2)-positive gastric cancer. However, whether
      expression of HER2 is related to prognosis of gastric cancer is still
      controversial. A total of 360 consecutive patients with gastric cancer who
      underwent surgical resection in our Department from 1994 to 2007 were analyzed.
      We performed immunohistochemical analysis of HER2 expression. HER2 expression
      level was classified into four scores (0, 1+, 2+ and 3+). There were 37 (10%)
      patients with a score of 3+. A score of 3+ was defined as being HER2-positive.
      Recurrence-free survival was worse in HER2-positive cases (p=0.045). When the
      analysis was conducted with intestinal types of cancer, RFS was considerably
      worse in the HER2-positive group (p=0.011). HER2 expression may have potential as
      a prognostic factor for intestinal cancer types. Further research is warranted. 

PMID- 25862913
TI  - High expression of phospho-H2AX predicts a poor prognosis in colorectal cancer.
AB  - BACKGROUND/AIM: Colorectal cancer (CRC) is one of the most common causes of
      cancer-related deaths worldwide. DNA double-strand breaks (DSBs) are deleterious
      lesions that can lead to chromosomal anomalies, genomic instability and cancer.
      The histone H2AX plays an important role in response to DNA damage and
      phosphorylation of H2AX (p-H2AX) is evidence of DSBs. The aim of this study was
      to evaluate the clinical significance of p-H2AX expression in CRC. PATIENTS AND
      METHODS: p-H2AX expression in CRC tissues was analyzed by immunohistochemistry
      and correlated with clinicopathological variables using the chi-square test. The
      prognostic value of p-H2AX for distant metastasis-free survival (DMFS) and
      overall survival (OS) was evaluated by Kaplan-Meier estimates and the individual
      prognostic components were analyzed with Cox regression analysis. RESULTS: A high
      p-H2AX expression in CRC tissues was associated with tumor stage and perineurial
      invasion. Furthermore, a high p-H2AX expression was associated with poor DMFS and
      OS. Cox regression analysis also revealed that p-H2AX was an independent
      predictor of DMFS and OS. CONCLUSION: A high p-H2AX expression in CRC tissues is
      associated with a more malignant cancer behavior, as well as poor patient
      survival. p-H2AX may, therefore, be an independent prognostic predictor for CRC,
      as well as a potential therapeutic target.

PMID- 25862914
TI  - MicroRNA profile in site-specific head and neck squamous cell cancer.
AB  - BACKGROUND/AIM: MicroRNAs (miRs) are non-coding RNA molecules regulating diverse
      cellular processes essential in carcinogenesis. Little is known regarding miRs in
      head and neck squamous cell cancer (HNSCC). The aim of the present study was to
      investigate miRs in relation to the clinico pathological features of site
      specific HNSCC. MATERIALS AND METHODS: The study comprised of 51 patients with
      HNSCC (23 oropharyngeal, 24 laryngeal and 4 hypopharyngeal carcinomas). Total RNA
      was extracted from tumor tissue and normal squamous epithelium using the miRNeasy
      FFPE Kit. A quantitative estimation of let-7a, miR-21, miR-200c, miR-34a, miR-375
      was performed by a real-time polymerase chain reaction (PCR) method using the
      TagMan(r) MicroRNA assay. Additionally, p16 expression was detected by immuno
      histo chemistry. RESULTS: Significant differences of let-7a, miR-200c, miR-34a
      levels between oropharyngeal and laryngeal cancers were found (p<0.05). Compared
      to non-neoplastic tissues, miR-21, miR-200c, miR-34a were up-regulated and miR
      375 was down-regulated in tumors of all sites. MiR-34a tumor levels significantly
      correlated with oropharyngeal origin (p=0.0284) and p16 positivity (p=0.0218).
      CONCLUSION: The microRNA profile seems to play a potential role in the
      pathobiology of oropharyngeal and laryngeal HNSCC. Up-regulation of miR34a in p16
      positive oropharyngeal cancer has not been so far described and additional
      studies are warranted.

PMID- 25862915
TI  - The clinical significance of activated p-AKT expression in peripheral T-cell
      lymphoma.
AB  - BACKGROUND: The oncogenic PI3K/serine-threonine kinase (PI3K/AKT) pathway is a
      downstream pathway of B-cell receptor (BCR) signaling pathway and plays a crucial
      role in the pathogenesis of B-cell lymphoma. However, there have been preclinical
      data showing PI3K/AKT pathway activation in T-cell lymphoma, with in different
      mechanisms from those in B-cell lymphoma. In this study, we investigated the
      impact of p-AKT expression on clinical outcomes of peripheral T-cell lymphoma
      (PTCL). MATERIALS AND METHODS: We analyzed 63 patients with PTCL [PTCL-not
      otherwise specified (NOS), angioimmunoblastic T-cell lymphoma (AITL), anaplastic
      large cell lymphoma (ALCL) or extranodal natural kiler T-cell lymphoma (NKTCL)].
      To define the clinical implications of p-AKT expression in PTCL, we calculated
      arbitrary units (AUs) by multiplying the intensity and the proportion of p-AKT
      expression. RESULTS: Based on a cutoff value of the upper limit of the third
      quartile (Q3) of the AU, 12 patients were classified into the high p-AKT group,
      while the remaining 51 patients were classified into the low p-AKT group. The
      overall response rate to frontline chemotherapy was significantly lower in the
      high p-AKT group than in the low p-AKT group (20.0% vs. 71.1%, p=0.004). The high
      p-AKT group showed substantially worse overall survival (OS) (median OS=2.3 vs.
      25.2 months, p<0.001) and progression-free survival (PFS) (median PFS=1.6 vs. 8.8
      months, p<0.001) compared with the low p-AKT group. Multivariate analysis showed
      that high p-AKT expression remained a significant independent poor prognostic
      factor for OS (hazard ratio (HR)=7.0; 95% confidence interval (CI)=3.0-16.6;
      p<0.001) and PFS (HR=6.8; 95% CI=3.0-15.2; p<0.001). CONCLUSION: PTCL patients
      with high p-AKT expression showed aggressive clinical courses with significantly
      worse OS and PFS and a poor chemotherapy response rate. We suggest that targeting
      the PI3K/AKT pathway may be a promising therapeutic strategy for PTCL.

PMID- 25862916
TI  - Long-term outcome of living-donor liver transplantation for combined
      hepatocellular-cholangiocarcinoma.
AB  - BACKGROUND/AIM: Combined hepatocellular-cholangiocarcinoma (cHC-CC) is found
      unexpectedly in explanted or resected liver specimens. The current study
      evaluated the longterm outcomes of living-donor liver transplantation (LDLT)
      between patients with cHC-CC and hepatocellular carcinoma (HCC). PATIENTS AND
      METHODS: We performed 178 LDLT including 8 patients of pathologically and
      immunohistochemically diagnosed cHC-CC who all underwent LDLT with a preoperative
      diagnosis of HCC by imaging study. RESULTS: Out of the 8 patients, 6 were within
      the Milan criteria and all were within the Kyushu University criteria. The 1-, 5-
      and 10-year overall survival (OS) and disease-free survival (DFS) rates after
      LDLT for patients with cHC-CC were 87.5, 72.9 and 48.6% and 85.7, 85.7 and 85.7%,
      respectively. The OS and DFS between patients with cHC-CC and HCC were not
      statistically different. CONCLUSION: LDLT for patients with cHC-CC using the
      Milan criteria or the Kyushu University criteria, as well as HCC, could have an
      acceptable long-term outcome.

PMID- 25862917
TI  - Errata.

PMID- 25862918
TI  - Retraction.

PMID- 25862919
TI  - Evidence for rapid ecological range expansion in a newly invasive plant.
AB  - Little is known about how an introduced species may expand its ecological range,
      i.e. the set of local environmental conditions in which it can successfully
      establish populations. Delimiting this range of conditions is a methodological
      challenge, because it is impossible to sample all potential field locations for
      any species in a given region. Developing approaches to track ecological range
      over time could substantially contribute to understanding invasion dynamics. In
      this study, we use a previously established sampling strategy to document
      apparent changes across a 15-year time interval in the ecological range of the
      Asian annual Polygonum cespitosum Blume in northeastern North America, where the
      species has recently become invasive. Using a structured sample drawn from a
      large set of field populations, we determined the range of light, soil moisture
      and soil nutrient conditions that the species currently occupies in this region
      and the proportional distribution of individuals in differing types of microsite,
      and compared them with field measurements that were similarly determined 15 years
      earlier. Although in 1994 the species was absent from both high-light and flooded
      habitats, in 2009 P. cespitosum occurred in open as well as shaded habitats,
      across a wide range of moisture conditions. In 2009 the species also occupied a
      greater proportion of high-light microsites within field sites than in 1994.
      These findings suggest an expanded ecological range that, intriguingly, is
      consistent with the recent evolution in North American P. cespitosum populations
      of adaptive plasticity in response to high light. Possible non-evolutionary
      explanations for the change in field distribution are also considered. 

PMID- 25862920
TI  - Diversity of sexual systems within different lineages of the genus Silene.
AB  - Species and populations can be categorized by their sexual systems, depending on
      the spatial distribution of female and male reproductive structures within and
      among plants. Although a high diversity of sexual systems exists in Silene, their
      relative frequency at the genus and infrageneric level is unknown. Here, we
      carried out an extensive literature search for direct or indirect descriptions of
      sexual systems in Silene species. We found descriptions of sexual systems for 98
      Silene species, where 63 and 35 correspond to the phylogenetically supported
      subgenera Silene and Behenantha, respectively. Hermaphroditism was the commonest
      sexual system (58.2 %), followed by dioecy (14.3 %), gynodioecy (13.3 %) and
      gynodioecy-gynomonoecy (i.e. hermaphroditic, female and gynomonoecious plants
      coexisting in the same population; 12.2 %). The presence of these sexual systems
      in both subgenera suggests their multiple origins. In 17 species, the description
      of sexual systems varied, and in most cases these differences corresponded to
      variations within or among populations. Interestingly, the poorly studied
      gynodioecy-gynomonoecy sexual system showed similar frequency to dioecy and
      gynodioecy in both subgenera. In addition, the incidence of gynodioecy
      gynomonoecy was analysed in the species of section Psammophilae (Silene littorea,
      S. psammitis, S. adscendens and S. cambessedesii), in a survey of 26 populations
      across the distribution area of the species. The four species showed gynomonoecy
      gynodioecy in most populations. Hermaphrodites were the most frequent morph, with
      a low number of females and gynomonoecious plants in all populations. The
      frequency of sexual morphs varied significantly among the studied populations but
      not among species. Female plants generally produced smaller numbers of flowers
      than hermaphroditic or gynomonoecious plants, and the percentages of female
      flowers per population were low. All these findings suggest that the
      gynodioecious-gynomonoecious sexual system in section Psammophilae is closer to
      hermaphroditism or gynomonoecy than gynodioecy. 

PMID- 25862921
TI  - Release of cardiac troponin using a high sensitivity assay after exercise: Type 2
      acute myocardial infarction?
AB  - BACKGROUND: Cardiac troponin is used as a marker for all types of myocardial
      infarction. METHODS: Assays for high-sensitivity troponin T and I were performed
      before, immediately and 24h after a 40 km bicycle ride in two middle aged
      individuals. RESULTS: There was a significant increase in cardiac troponin
      immediately after exercise in both individuals. This was accompanied by a return
      to baseline levels within 24h. A CT angiogram was normal in one while the other
      had a significant occlusion in the mid-right coronary artery. After a stent
      placement, in this latter individual, there was no major increase in troponin
      after a second bicycle ride. CONCLUSIONS: Using high sensitivity assays, at least
      one of these two subjects may have suffered a type 2 myocardial infarction had
      the increases in hs-cTnI were accompanied by other acceptable evidence of
      myocardial ischemia (symptoms, ECG, etc.).

PMID- 25862922
TI  - In silico prediction and validation of potential gene targets for pospiviroid
      derived small RNAs during tomato infection.
AB  - Viroids are small, covalently closed, circular non-coding RNA pathogens of
      flowering plants. It is proposed that the symptoms of viroid pathogenesis result
      from a direct interaction between the viroid genomic RNA and unknown host plant
      factors. Using a comparative genomic approach we took advantage of the detailed
      annotation of the Arabidopsis thaliana (Arabidopsis) genome to identify sequence
      homologies between putative viroid-derived small RNAs (vd-sRNAs) and coding
      regions in the plant genome. A pool of sequence homologies among 29 species of
      the Pospiviroidae family and the Arabidopsis genome was analyzed. Using this
      strategy we identified putative host gene targets that may be involved in symptom
      expression in viroid-infected plants. In this communication, we report the in
      silico prediction and the experimental validation of pospiviroid-derived sRNAs
      conserved in the lower strand of the pathogenicity domain of seven viroid species
      infecting tomato; those vd-sRNAs targeted for cleavage the host mRNA encoding a
      conserved tomato WD40-repeat protein (SolWD40-repeat; SGN_U563134). Analysis of
      SolWD40-repeat expression indicated that this gene is down-regulated in tomato
      plants infected with tomato planta macho viroid (TPMVd). Furthermore, 5' RLM-RACE
      revealed that the SolWD40-repeat mRNA is cleaved at the predicted target site
      showing complementarity to a corresponding TPMVd-sRNA identified in silico. Our
      approach proved to be useful for the identification of natural host genes
      containing sequence homologies with segments of the Pospiviroidae genome. Using
      this strategy we identified a functionally conserved gene in Arabidopsis and
      tomato, whose expression was modified during viroid infection in the host genome;
      regulation of this gene expression could be guided by vd-sRNA:mRNA
      complementarity, suggesting that the comparison of the Arabidopsis genome to
      viroid sequences could lead to the identification of unexpected interactions
      between viroid RNAs and their host.

PMID- 25862923
TI  - Hydroxymethylation and its potential implication in DNA repair system: A review
      and future perspectives.
AB  - The 5-hydroxymethylcytosine (5-hmC) is known to exist as a predictive indicator
      for a variety of cancers, neurological abnormalities and other perilous diseases.
      The precursor of 5-hmC i.e. 5-methylcytosine (5mC) has already gained attention
      as an important epigenetic regulator whereas 5-hmC remains less explored. The two
      modified DNA bases (5mC and 5-hmC) have absolute diverse distribution, i.e. 5-hmC
      is mostly restrained to the 5' end of DNA with levels directing the gene
      transcription whereas 5mC is mainly located at the intra- or intergenic regions
      of DNA repeats and within certain gene bodies. It has been reported that levels
      of 5-hmC in different tissues provide a useful tool for detecting numerous
      associated diseases and their progression. Therefore, to unravel the role of
      hydroxymethylation in various resulting diseases in humans, comprehensive
      information on this crucial process has been explored and compiled for its
      implication in DNA repair system. The role of miRNAs in cancer through hypo- and
      hypermethylation has also been explored and discussed. In this review, a broad
      and exclusive insight into hydroxymethylation and its association with repair
      mechanisms is extensively presented and it is estimated that the accessible
      information will be of utmost use to the biological community working in the
      relevant research area. 

PMID- 25862924
TI  - Molecular characterization of an estrogen receptor and estrogen-related receptor
      and their autoregulatory capabilities in two Mytilus species.
AB  - Vertebrate-like sex steroid hormones have been widely detected in mollusks, and
      numerous experiments have shown the importance of steroids in gonad development.
      Nevertheless, their signaling pathways in invertebrates have not been uncovered
      yet. Steroid receptors are an ancient class of transcription factors with
      multiple roles in not only vertebrates but also invertebrates. Estrogen signaling
      is thought to have major roles in mollusk physiology, but the full repertoire of
      estrogen receptors is unknown. We presented the successful cloning of two novel
      forms of estrogen receptor-like genes. These receptors are present in two closely
      related species of Mytilus: Mytilus edulis and Mytilus galloprovincialis,
      commonly known and widely distributed sentinel species. Our phylogenetic analysis
      revealed that one of these receptors is an estrogen receptor (ER) and the other
      one is an estrogen-related receptor (ERR). Studies of expression analysis showed
      that both receptor mRNAs were localized in the oocytes and follicle cells in
      contact with developing oocytes in the ovary and Sertoli cells in the testis, and
      in the ciliated cells of the gill. In addition, we have evidence that one (ER) of
      these may have a capacity to autoregulate its own expression in the gonadal cells
      by estrogen (E2) and that this gene is responsive to estrogenic compounds. 

PMID- 25862925
TI  - In vivo reversion of an inherited mutation in a Chinese patient with Wiskott
      Aldrich syndrome.
AB  - A spontaneous reversion that restores Wiskott-Aldrich syndrome protein (WASP)
      expression was reported recently. However, the genetic mechanism underlying the
      reversion event was unclear. In the present study, a WAS patient with a nonsense
      mutation (155 C>T, R41X) was followed during a three-year period. No expression
      of WASP was detected in peripheral blood mononucleated cells (PBMCs) in 2009 and
      a small population of intracellular WASP positive lymphocytes was detected during
      the following three years. The increasing trend of the revertant genotype was
      significant. WASP-expressing cells were present mainly CD56+ NK cells and CD8+ T
      cells. Sorted WASP+ cells were analyzed, indicating that the population of CD3+ T
      cells increased from 36.81% to 99.8%. Although the revertant cells in vivo may
      have a growth advantage, the patient presented a persistent autoimmune disease,
      thrombocytopenia, and died from extensive pulmonary fibrosis. The results suggest
      that the clinical consequences of T-cell mosaicism in WAS remain difficult to
      predict and is not sufficient to fully normalize immune functions in patients
      with WAS. 

PMID- 25862927
TI  - Calcification of the Seminal Vesicles.

PMID- 25862928
TI  - Measuring positive emotions in cows: Do visible eye whites tell us anything?
AB  - Insight into the emotional lives of animals is of utmost importance to the
      welfare of the billions of animals in our care, yet little is known about how to
      measure these states. Scientific understanding of how to measure and interpret
      positive emotional states is particularly lacking, although recent years have
      seen a notable increase in such studies. This study explored whether the
      percentage of visible eye whites is a valid measure of a low arousal, positive
      emotional state in dairy cows (Bos taurus), by using stroking as the positive
      stimulus. Thirteen dairy cows were studied over a period of two months, and a
      total of 372 full 15minute focal observations were performed. Each focal
      observation comprised three 5minute phases: pre-stroking (baseline), stroking
      (stimulus), and post-stroking (post-stimulus), and the focal cow's behaviours
      were recorded throughout each observation, and the focal eye was filmed for later
      analysis. Following data collection we calculated the percentage of visible eye
      white at nine pre-determined measurement points throughout each focal
      observation. The eye white data were analysed using the one-way repeated measures
      ANOVA test. The percentage of visible eye white dropped during stroking compared
      with during both the pre-stroking and post-stroking phases (ANOVA: F1.242,
      14.9=4.32, P=0.025). The behaviours were analysed using Friedman's ANOVA and
      Wilcoxon's signed-rank test. Behaviours known to be associated with positive
      emotions in cows were performed during the stroking phase of the focal
      observation, supporting the use of stroking as a stimulus to induce a positive,
      low arousal emotional state. This study has explored the potential of visible eye
      whites as a measure of positive emotions and arousal, and our results support
      previous studies which suggest that eye whites may serve as a dynamic measure of
      emotion and arousal. 

PMID- 25862929
TI  - Growing an editorial board for an ever expanding field.

PMID- 25862930
TI  - Rhodopsin on tracks: new ways to go in signaling.
AB  - In this issue of Structure, Gunkel et al. describe cryoelectron tomography
      analysis of the nano-organization of the G protein-coupled receptor (GPCR)
      rhodopsin in the rod photoreceptor disk membranes in a near-native environment.
      Their data strongly suggest that rhodopsin is organized in the native rod disk as
      dimers arranged in parallel tracks aligned to the incisure. 

PMID- 25862931
TI  - The molecular basis for the substrate specificity of protein tyrosine phosphatase
      PTPN3.
AB  - In this issue of Structure, Chen et al. present structures of the FERM-containing
      protein tyrosine phosphatase PTPN3 in complex with a phosphopeptide fragment of
      substrate epidermal growth factor receptor pathway substrate, providing detailed
      information on substrate specificity.

PMID- 25862932
TI  - Splicing and proteolytic processing in VEGF signaling: now it is the coreceptor's
      turn.
AB  - Alternative splicing and proteolytic processing of VEGFs generate proteins with
      distinct physiological roles. In this issue of Structure, Parker et al. show that
      proteolysis of an isoform of the VEGF-C coreceptor Nrp2 produces a soluble
      receptor that inhibits VEGF-C/Nrp2 interactions. 

PMID- 25862933
TI  - May the force be with you: unfolding lipid-protein interactions by single
      molecule force spectroscopy.
AB  - In this issue of Structure, Serdiuk et al. report the use of single-molecule
      force microscopy to establish a role for phosphatidylethanolamine in promoting
      the native fold of lactose permease, thereby preventing it from populating a
      functionally defective, nonnative conformation (Serdiuk et al., 2015). 

PMID- 25862934
TI  - Comparative analysis of milk fat decomposition activity by Mrakia spp. isolated
      from Skarvsnes ice-free area, East Antarctica.
AB  - Milk fat curdle is difficult to remove from sewage. In an attempt to identify an
      appropriate agent for bio-remediation of milk fat curdle, Mrakia strains were
      collected from the Skarvsnes ice-free area of Antarctica. A total of 27 strains
      were isolated and tested for their ability to decompose milk fat at temperatures
      ranging from 4 degrees C to 15 degrees C. All strains could decompose milk fat at
      4 degrees C and 10 degrees C. Phylogenetic analysis and comparison of the
      decomposition ability of milk fat (DAMF) revealed that the DAMF may be useful for
      predicting the outcome of phylogenetic analysis based on ITS sequences.

PMID- 25862935
TI  - Meningioma in Down Syndrome.
AB  - BACKGROUND: Down syndrome comprises multiple malformations and is due to trisomy
      of chromosome 21. There is epidemiologic evidence that individuals with Down
      syndrome are at decreased risk for solid tumors including brain tumors. It has
      been suggested that some genes expressed on the extra copy of chromosome 21 act
      as tumor suppressor genes and contribute to protection against tumorigenesis.
      CASE DESCRIPTION: We report the first case to our knowledge of a patient with
      Down syndrome, an 8-year-old boy, with an intracranial meningioma, in which the
      status of chromosome 21 was examined. The diagnosis was based on histologic
      examination of the surgically resected tumor. Postoperatively, the patient's
      neurologic status improved, and there was no tumor regrowth in the next 2 years.
      Fluorescence in situ hybridization for chromosome 22 confirmed high allele loss
      involving the neurofibromin 2 gene locus, a finding typical in meningiomas.
      Fluorescence in situ hybridization also revealed chromosome 21 heterogeneity in
      tumor cells; not only cells with trisomy 21 but also cells with disomy and
      monosomy 21 were present. All blood cells from the patient manifested trisomy 21.
      CONCLUSIONS: Deletion of the chromosome 21 allele may be associated with
      tumorigenesis of meningioma in Down syndrome. This supports the hypothesis that
      some genes whose expression is increased on the extra copy of chromosome 21
      function as tumor suppressor genes and that they contribute to the reduced tumor
      incidence in individuals with Down syndrome.

PMID- 25862936
TI  - LH and testosterone production are more sensitive to the suppressive effects of
      food deprivation in prenatally undernourished male rats.
AB  - Although prenatal undernutrition affects the development of metabolic,
      physiological, and reproductive functions, it remains unclear whether it also
      affects physiological responses to undernutrition in adulthood. Therefore, in
      this study we examined whether prenatal undernutrition alters the sensitivity of
      the hypothalamic-pituitary-gonadal (HPG) axis to fasting in adult male rats. The
      offspring of ad libitum fed dams (control) and ~50% food-restricted (during the
      late gestational period) dams (IUGR) were sub-divided into ad libitum fed (fed)
      and 48 h food deprivation (FD) groups at 10 weeks of age. In each group, the
      serum levels of luteinizing hormone (LH), testosterone, and leptin and the
      hypothalamic mRNA expression levels of gonadotropin-releasing hormone (GnRH)
      regulatory factors were measured. The serum LH and testosterone levels of the
      IUGR-fed rats were significantly or tend to be higher than those of the control
      fed rats, respectively. The serum LH levels of the IUGR-FD rats were lower than
      those of the IUGR-fed rats. Similarly, the serum testosterone levels of the IUGR
      FD rats tended to be lower than those of the IUGR-fed rats. On the other hand,
      the serum LH and testosterone levels of the control-fed and control-FD rats did
      not differ. The serum leptin levels of the IUGR fed rats were higher than those
      of the control-fed rats. The serum leptin levels of the control-FD and IUGR-FD
      rats were lower than those of the control-fed and IUGR-fed rats, respectively.
      The hypothalamic neuropeptide Y (NPY) mRNA levels of the IUGR-FD rats were higher
      than those of the IUGR-fed rats. Similarly, hypothalamic NPY mRNA levels of
      control-FD rats were higher than those of the control-fed rats. The hypothalamic
      kisspeptin, kisspeptin receptor, RFamide-related peptide, GPR147, and OBRb mRNA
      levels of control fed rats did not differ between control-fed and IUGR-fed rats.
      Their mRNA levels of the fed and FD rats did not differ in the control or IUGR
      groups. These results suggested that prenatal undernutrition increased the basal
      LH and testosterone production, whereas they are easily reduced by food
      deprivation in male rats. Changes of serum leptin level, but not of hypothalamic
      reproductive related factors, might be involved in these alterations. However,
      the precise mechanisms responsible for these effects remain unclear.

PMID- 25862937
TI  - Autistic spectrum disorders: A review of clinical features, theories and
      diagnosis.
AB  - Autism spectrum disorder (ASD) is a set of neurodevelopmental disorders that is
      among the most severe in terms of prevalence, morbidity and impact to the
      society. It is characterized by complex behavioral phenotype and deficits in both
      social and cognitive functions. Although the exact cause of ASD is still not
      known, the main findings emphasize the role of genetic and environmental factors
      in the development of autistic behavior. Environmental factors are also likely to
      interact with the genetic profile and cause aberrant changes in brain growth,
      neuronal development, and functional connectivity. The past few years have seen
      an increase in the prevalence of ASD, as a result of enhanced clinical tests and
      diagnostic tools. Despite growing evidence for the involvement of endogenous
      biomarkers in the pathophysiology of ASD, early detection of this disorder
      remains a big challenge. This paper describes the main behavioral and cognitive
      features of ASD, as well as the symptoms that differentiate autism from other
      developmental disorders. An attempt will be made to integrate all the available
      evidence which point to reduced brain connectivity, mirror neurons deficits, and
      inhibition-excitation imbalance in individuals with ASD. Finally, this review
      discusses the main factors involved in the pathophysiology of ASD, and
      illustrates some of the most important markers used for the diagnosis of this
      debilitating disorder. 

PMID- 25862938
TI  - Neuroprotective role of an N-acetyl serotonin derivative via activation of
      tropomyosin-related kinase receptor B after subarachnoid hemorrhage in a rat
      model.
AB  - N-[2-(5-hydroxy-1H-indol-3-yl) ethyl]-2-oxopiperidine-3-carboxamide (HIOC), an N
      acetyl serotonin derivative, selectively activates tropomyosin-related kinase
      receptor B (TrkB). This study is to investigate a potential role of HIOC on
      ameliorating early brain injury after experimental subarachnoid hemorrhage (SAH).
      One hundred and fifty-six adult male Sprague-Dawley rats were used. SAH model was
      induced by endovascular perforation. TrkB small interfering RNA (siRNA) or
      scramble siRNA was injected intracerebroventricularly 24h before SAH. HIOC was
      administrated intracerebroventricularly 3h after SAH and compared with brain
      derived neurotrophic factor (BDNF). SAH grade and neurologic scores were
      evaluated for the outcome study. For the mechanism study, the expression of TrkB,
      phosphorylated TrkB (p-TrkB), phosphorylated extracellular signal regulated
      kinase (p-ERK), B-cell lymphoma 2 (Bcl-2) and cleaved caspase 3 (CC3) was
      detected by Western blots, and neuronal injury was determined by double
      immunofluorescence staining of neuronal nuclei and terminal deoxynucleotidyl
      transferase-mediated uridine 5'-triphosphate-biotin nick end-labeling. Knocking
      down of TrkB decreased the expression of Bcl-2 and aggravated neurologic deficits
      24h after SAH. HIOC activated TrkB/ERK pathway, decreased neuronal cell death,
      and improved neurobehavioral outcome, and these effects were abolished by TrkB
      siRNA. HIOC was more potent than BDNF in reduction of apoptosis 24h post-SAH.
      Thus, we conclude that administration of HIOC activated TrkB/ERK signaling
      cascade and attenuated early brain injury after SAH. HIOC may be a promising
      agent for further treatment for SAH and other stroke events. 

PMID- 25862939
TI  - Increased 14-3-3 phosphorylation observed in Parkinson's disease reduces
      neuroprotective potential of 14-3-3 proteins.
AB  - 14-3-3 proteins are key regulators of cell survival. We have previously
      demonstrated that 14-3-3 levels are decreased in an alpha-synuclein (alphasyn)
      mouse model of Parkinson's disease (PD), and that overexpression of certain 14-3
      3 isoforms is protective in several PD models. Here we examine whether changes in
      14-3-3 phosphorylation may contribute to the neurodegenerative process in PD. We
      examine three key 14-3-3 phosphorylation sites that normally regulate 14-3-3
      function, including serine 58 (S58), serine 184 (S184), and serine/threonine 232
      (S/T232), in several models of PD and in human PD brain. We observed that an
      increase in S232 phosphorylation is observed in rotenone-treated neuroblastoma
      cells, in cells overexpressing alphasyn, and in human PD brains. Alterations in
      S58 phosphorylation were less consistent in these models, and we did not observe
      any phosphorylation changes at S184. Phosphorylation at S232 induced by rotenone
      is reduced by casein kinase inhibitors, and is not dependent on alphasyn.
      Mutation of the S232 site affected 14-3-3theta's neuroprotective effects against
      rotenone and 1-methyl-4-phenylpyridinium (MPP(+)), with the S232D mutant lacking
      any protective effect compared to wildtype or S232A 14-3-3theta. The S232D mutant
      partially reduced the ability of 14-3-3theta to inhibit Bax activation in
      response to rotenone. Based on these findings, we propose that phosphorylation of
      14-3-3s at serine 232 contributes to the neurodegenerative process in PD. 

PMID- 25862941
TI  - Change in serum marker of oxidative stress in the progression of idiopathic
      pulmonary fibrosis.
AB  - BACKGROUND: Increased oxidative stress is supposed to be involved in the etiology
      of idiopathic pulmonary fibrosis (IPF). It was reported that oxidative stress
      values measured by a spectrophotometric technique (d-ROMs test) were
      significantly higher in IPF patients than in controls, and were negatively
      correlated with Forced Vital Capacity (FVC) and Carbon Monoxide Diffusing
      Capacity (DLCO). However, the relationship between progression of IPF over time
      and change in serum oxidative stress marker remains unclarified. AIMS: This study
      aimed to investigate the change in serum oxidative stress marker during
      progression of IPF. SUBJECTS AND METHODS: The levels of oxidative stress in blood
      samples of 43 treatment-naive IPF patients were measured by the d-ROMs test. FVC
      and DLCO were measured concurrently. The changes in oxidative stress and
      pulmonary function were evaluated in 27 untreated patients 6 months later.
      Oxidative stress levels of 13 patients with acute exacerbation of IPF (AE-IPF)
      and 30 healthy controls were also evaluated. RESULTS: Oxidative stress values
      [median, interquartile range (IQR); Carratelli units (U.CARR)] were significantly
      higher in 43 IPF patients than in controls (366, 339-443 vs. 289, 257-329, p <
      0.01) and were significantly increased 6 months later in 27 untreated patients
      (353, 311-398 at baseline to 385, 345-417 at follow-up, p < 0.01). The increase
      in oxidative stress values (24.0, 6.0-49.0 U.CARR/6 months) was negatively
      correlated with baseline DLCO (rs = -0.44, p < 0.05) and FVC changes after 6
      months (rs = -0.54, p < 0.01). Oxidative stress values were significantly higher
      in IPF patients with acute exacerbation than in those with stable disease (587,
      523-667 vs. 366, 339-443 U.CARR, respectively; p < 0.01). CONCLUSIONS: Serum
      oxidative stress values increased with disease progression in IPF patients.

PMID- 25862940
TI  - Thalamic structures and associated cognitive functions: Relations with age and
      aging.
AB  - The thalamus, with its cortical, subcortical, and cerebellar connections, is a
      critical node in networks supporting cognitive functions known to decline in
      normal aging, including component processes of memory and executive functions of
      attention and information processing. The macrostructure, microstructure, and
      neural connectivity of the thalamus changes across the adult lifespan. Structural
      and functional magnetic resonance imaging (MRI) and diffusion tensor imaging
      (DTI) have demonstrated, regional thalamic volume shrinkage and microstructural
      degradation, with anterior regions generally more compromised than posterior
      regions. The integrity of selective thalamic nuclei and projections decline with
      advancing age, particularly those in thalamofrontal, thalamoparietal, and
      thalamolimbic networks. This review presents studies that assess the relations
      between age and aging and the structure, function, and connectivity of the
      thalamus and associated neural networks and focuses on their relations with
      processes of attention, speed of information processing, and working and episodic
      memory. 

PMID- 25862942
TI  - Characterizing brain iron deposition in subcortical ischemic vascular dementia
      using susceptibility-weighted imaging: An in vivo MR study.
AB  - The aim of this study was to investigate the brain iron accumulation in
      subcortical ischemic vascular dementia (SIVD) and its correlation with the
      severity of cognitive impairment. Thirty five patients with SIVD and 35 healthy
      controls underwent high-resolution susceptibility-weighted imaging. The phase
      shift value of the bilateral hippocampus (HP), caudate nucleus (CN), globus
      pallidus (GP), putamen (PU), thalamus (TH), red nucleus (RN), substantia nigra
      (SN), anterior cingulate cortex (ACC), posterior cingulate (PCC), parietal cortex
      (PC) and frontal white matter (FWM) were examined and correlated with
      neuropsychological scores for SIVD patients. They exhibited significant increased
      phase shift values in the bilateral HP, CN, PU, right GP and left SN (P<0.05).
      Close correlations were found between the phase shift value of the left HP, right
      CN and neuropsychological scores. Our results suggest that brain iron deposition
      may be a biomarker of SIVD and play an important role in the pathophysiological
      mechanism. 

PMID- 25862943
TI  - Adenosine A2A receptor-mediated control of pilocarpine-induced tremulous jaw
      movements is Parkinson's disease-associated GPR37 receptor-dependent.
AB  - GPR37, also known as parkin associated endothelin-like receptor (Pael-R), is an
      orphan GPCR that aggregates intracellularly in a juvenile form of Parkinson's
      disease. However, little is known about the function of this orphan receptor.
      Here, using a model for parkisonian tremor, the pilocarpine-induced tremulous jaw
      movements (TJMs), we show that the deletion of GPR37 attenuated the TJMs in
      response to this cholinomimetic. Interestingly, the control that adenosine A2A
      receptor exerted over TJMs was lost in the absence of GPR37, thus pointing to a
      pivotal role of this orphan receptor in the adenosinergic control of parkinsonian
      tremor. 

PMID- 25862944
TI  - ATP decreases mechanical sensitivity of muscle thin-fiber afferents in rats.
AB  - ATP is an energy rich substance contained in cells in the order of mM. It is
      released when cells are damaged and when muscle is compressed or contracted.
      Subcutaneous injection of ATP induces pain-related behavior and hyperalgesia to
      mechanical and heat stimulation in rats. However, the effects of ATP in muscle
      have not been fully studied. In the present study we examined the effects of ATP
      on muscle C-fiber afferent activities using single fiber recordings, and on
      nociceptive behavior. Muscle C-fiber activities were recorded in vitro using
      extensor digitorum longus muscle-common peroneal nerve preparations excised from
      rats deeply anesthetized with pentobarbital. ATP (100 MUM and 1 mM, but not 1
      MUM) superfused for 5 min before the mechanical stimulation suppressed the
      mechanical responses of muscle thin fibers irrespective of whether they excited
      the fiber. This suppressive effect was reversed by P2X receptor antagonists PPADS
      (100 MUM) and suramin (300 MUM). We also found that subcutaneous injection of ATP
      (10 mM) induced nociceptive behavior, whereas intramuscular injection had no
      effect. These findings showed that effects of ATP on muscle afferents differ from
      those on cutaneous afferents.

PMID- 25862946
TI  - Common side reactions of the glycosyl donor in chemical glycosylation.
AB  - Chemical glycosylation is central to carbohydrate chemistry and is generally
      recognised as a challenging reaction. This review describes the most reoccurring
      side reactions of glycosyl donors in glycosylation and how scientists have
      attempted to explain their observations and in some cases succeeded in solving a
      particular encountered problem. The topics covered are donor hydrolysis,
      elimination to form glycals, intermolecular aglycon transfer of thioglycosides
      and glycosyl imidate rearrangement. 

PMID- 25862945
TI  - Programmed cell death in aging.
AB  - Programmed cell death (PCD) pathways, including apoptosis and regulated necrosis,
      are required for normal cell turnover and tissue homeostasis. Mis-regulation of
      PCD is increasingly implicated in aging and aging-related disease. During aging
      the cell turnover rate declines for several highly-mitotic tissues. Aging
      associated disruptions in systemic and inter-cell signaling combined with cell
      autonomous damage and mitochondrial malfunction result in increased PCD in some
      cell types, and decreased PCD in other cell types. Increased PCD during aging is
      implicated in immune system decline, skeletal muscle wasting (sarcopenia), loss
      of cells in the heart, and neurodegenerative disease. In contrast, cancer cells
      and senescent cells are resistant to PCD, enabling them to increase in abundance
      during aging. PCD pathways limit life span in fungi, but whether PCD pathways
      normally limit adult metazoan life span is not yet clear. PCD is regulated by a
      balance of negative and positive factors, including the mitochondria, which are
      particularly subject to aging-associated malfunction. 

PMID- 25862947
TI  - Maximizing children's physical activity using the LET US Play principles.
AB  - BACKGROUND: Staff in settings that care for children struggle to implement
      standards designed to promote moderate-to-vigorous physical activity (MVPA),
      suggesting a need for effective strategies to maximize the amount of time
      children spend in MVPA during scheduled PA opportunities. The purpose of this
      study was to compare the MVPA children accumulate during commonly played games
      delivered in their traditional format versus games modified according to the LET
      US Play principles. METHODS: Children (K-5th) participated in 1-hour PA sessions
      delivered on non-consecutive days (summer 2014). Using a randomized,
      counterbalanced design, one of the six games was played for 20min using either
      traditional rules or LET US Play followed by the other strategy with a 10min
      break in between. Physical activity was measured via accelerometry. Repeated
      measures, mixed-effects regression models were used to estimate differences in
      percent of time spent sedentary and in MVPA. RESULTS: A total of 267 children
      (age 7.5years, 43% female, 29% African American) participated in 50, 1-hour
      activity sessions. Games incorporating LET US Play elicited more MVPA from both
      boys and girls compared to the same games with traditional rules. For boys and
      girls, the largest MVPA difference occurred during tag games (+20.3%). The
      largest reduction in the percent of time sedentary occurred during tag games
      (boys -27.7%, girls -32.4%). Overall, the percentage of children meeting 50% time
      in MVPA increased in four games (+18.7% to +53.1%). CONCLUSION: LET US Play led
      to greater accumulation of MVPA for boys and girls, and can increase the percent
      of children attaining the 50% of time in MVPA standard.

PMID- 25862948
TI  - A quantitative assay to monitor HSV-1 ICP0 ubiquitin ligase activity in vitro.
AB  - The ubiquitin-proteasome system is an essential cellular process that plays a
      fundamental role in the regulation of protein stability. This pathway is tightly
      controlled by a sequential cascade of enzymatic steps that culminates in the
      formation of a poly-ubiquitin chain onto the substrate protein targeted for 26S
      proteasome degradation. Through a process of co-evolution viruses have evolved
      mechanisms to utilize or suppress this pathway in order to enhance their
      replication and spread. One of the first proteins to be expressed during herpes
      simplex virus 1 (HSV-1) infection is ICP0, a viral RING-finger E3 ubiquitin
      ligase that targets a variety of cellular proteins for ubiquitination and
      proteasome-dependent degradation. This activity is required in order for ICP0 to
      efficiently stimulate the onset of HSV-1 lytic infection and viral reactivation
      from latency. While it is clear that the RING-finger domain of ICP0 plays an
      important role in the biology of HSV-1, methods for accurately quantifying its
      biochemical activity are currently lacking. Here we describe a protocol that
      enables the quantitative measurement of the ubiquitin ligase activity of ICP0
      using near-infrared (IR) western blot imaging. The use of such imaging technology
      provides an accurate means to examine the biochemical and kinetic parameters of
      RING-finger ubiquitin ligases in solution, and may provide significant
      application for inhibitor studies. 

PMID- 25862949
TI  - Correlation between SUVA and DBP formation during chlorination and chloramination
      of NOM fractions from different sources.
AB  - Natural organic matter (NOM) is the major precursor to the formation of
      disinfection byproducts (DBPs) during drinking water treatment. Specific
      ultraviolet absorbance (SUVA) is a widely used surrogate parameter to
      characterize NOM and predict its DBP formation potential. The objective of this
      study was to determine the relationships between SUVA and different classes of
      DBPs formed by NOM fractions from different sources. Three natural waters with a
      wide SUVA range were fractionated into differing hydrophobicity and molecular
      weight groups using XAD-4 and XAD-8 resins and ultrafiltration membranes. Each
      NOM fraction was treated with chlorine and monochloramine under controlled
      laboratory conditions. Different classes of DBPs showed different relationships
      with SUVA. SUVA correlated strongly with trihaloacetic acids (THAAs) and unknown
      total organic halogen (UTOX) yields whereas weak correlations were observed
      between SUVA and trihalomethane (THM) and dihaloacetic acid (DHAA) yields during
      chlorination. These results reinforce the hypothesis that DHAAs and THAAs form
      through different precursors and reaction pathways. Strong correlation between
      SUVA and UTOX was also observed during chloramination. However, no significant
      relationship was observed between SUVA and chloramination THMs and DHAAs.
      Overall, SUVA is a good indicator for the formation of unknown DBPs. This
      indicates that UV absorbing compounds and aromatic carbon within NOM are the
      primary sources of precursors for unknown DBPs.

PMID- 25862950
TI  - Editorial: Claude Klee, Sten Orrenius and Katsuhiko Mikoshiba.

PMID- 25862951
TI  - A personal anecdote of Ernesto Carafoli: Katsuhiko Mikoshiba.

PMID- 25862952
TI  - Tumor-infiltrating lymphocyte activity is enhanced in tumors with low IL-10
      production in HBV-induced hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is one of the most common cancers and can be
      induced by chronic HBV infection. The role of HBV-specific immune responses in
      mediating tumorigenesis and HCC prognosis is debated. The effect of intratumoral
      microenvironment on tumor-infiltrating lymphocytes (TILs) is also unclear. Here,
      we examined resected tumor tissue from 36 patients with HBV-induced HCC. We
      categorized study cohort based on ex vivo IL-10 secretion by tumor cells into
      high IL-10-secreting (Hi10) and low IL-10-secreting (Lo10) groups, and found that
      the Lo10 group was less sensitive to TLR ligand stimulation. TILs from the Lo10
      group contained higher frequencies of HBV-specific IFN-g-producing cells and
      total IFN-g-producing cells, and possessed higher proliferative capacity.
      Moreover, the proliferative capacity of TILs from the Hi10 group was negatively
      correlated with IL-10 secretion from tumor cells. Together, our data demonstrated
      that low IL-10-producing capacity in HBV-induced HCC tumors is associated with
      enhanced TIL activity. 

PMID- 25862954
TI  - Functional interaction between CTGF and FPRL1 regulates VEGF-A-induced
      angiogenesis.
AB  - Vascular endothelial growth factor-A (VEGF-A) is a master regulator of
      angiogenesis that controls several angiogenic processes in endothelial cells.
      However, the detailed mechanisms of VEGF-A responsible for pleiotropic functions
      and crosstalk with other signaling pathways have not been fully understood. Here,
      we found that VEGF-A utilizes the connective tissue growth factor (CTGF)/formyl
      peptide receptor-like 1 (FPRL1) axis as one of its mediators in angiogenesis.
      Using a proteomic approach, we found increased secretion of a matricellular
      protein, CTGF, from VEGF-A-treated human umbilical vein endothelial cells
      (HUVECs). Then, we studied the effect of CTGF binding to FPRL1 in VEGF-A-induced
      angiogenesis. CTGF directly binds to FPRL1 through a linker region and activates
      the downstream signals of FPRL1, such as increase in extracellular signal
      regulated kinase (ERK) phosphorylation and intracellular Ca(2+) concentration. We
      found that linker region-induced FPRL1 activation promotes the migration and
      network formation of HUVECs, while disruption of FPRL1 inhibits VEGF-A-induced
      HUVEC migration and network formation. In addition, similar results were observed
      by the chorioallantoic membrane (CAM) assay based evaluation of angiogenesis in
      vivo. To summarize, our data reveal a novel working model for VEGF-A-induced
      angiogenesis via the VEGF-A/CTGF/FPRL1 axis that might prolong and enhance the
      signals initiated from VEGF-A. 

PMID- 25862953
TI  - Observed parent-child relationship quality predicts antibody response to
      vaccination in children.
AB  - BACKGROUND: Quality of the parent-child relationship is a robust predictor of
      behavioral and emotional health for children and adolescents; the application to
      physical health is less clear. METHODS: We investigated the links between
      observed parent-child relationship quality in an interaction task and antibody
      response to meningococcal conjugate vaccine in a longitudinal study of 164
      ambulatory 10-11 year-old children; additional analyses examine associations with
      cortisol reactivity, BMI, and somatic illness. RESULTS: Observed
      Negative/Conflict behavior in the interaction task predicted a less robust
      antibody response to meningococcal serotype C vaccine in the child over a 6 month
      period, after controlling for socio-economic and other covariates. Observer rated
      interaction conflict also predicted increased cortisol reactivity following the
      interaction task and higher BMI, but these factors did not account for the link
      between relationship quality and antibody response. CONCLUSIONS: The results
      begin to document the degree to which a major source of child stress exposure,
      parent-child relationship conflict, is associated with altered immune system
      development in children, and may constitute an important public health
      consideration.

PMID- 25862955
TI  - Human exposure to PCDD/Fs and PCBs through consumption of fish and seafood in
      Catalonia (Spain): Temporal trend.
AB  - The concentrations of PCDD/Fs and 18 PCBs (DL- and NDL-) were analyzed in 16 fish
      and seafood species widely consumed in Catalonia (Spain). The exposure of these
      pollutants was subsequently estimated according to various groups of population.
      The concentrations of PCDD/Fs and PCBs showed an important decrease in relation
      to the baseline study (2000) and our last survey (2008). Sardine and red mullet
      were the species showing the highest pollutant concentrations, while canned tuna
      and cuttlefish presented the lowest levels. Sardine was the main contributor to
      the exposure of PCDD/Fs and PCBs. In contrast, swordfish was the species with the
      lowest contribution to the exposure of PCDD/Fs, DL-PCBs, and PCDD/Fs+DL-PCBs,
      while clam was the minor contributor for NDL-PCBs and total PCBs. For all groups
      of population, the current intakes of PCDD/Fs and PCBs were lower than the TDI (1
      4 pg WHO-TEQ/kg body weight/day), being children the group with the highest
      exposure. However, this exposure should not mean a health risk for this group of
      population. The current intake of PCDD/Fs and PCBs through fish and seafood
      consumption was similar or even lower than most values reported in recent studies
      all over the world.

PMID- 25862957
TI  - Investigation of lead and cadmium in counterfeit cigarettes seized in the United
      States.
AB  - Information of toxic elements such as lead (Pb) and cadmium (Cd) in counterfeit
      cigarettes offers insight on the potential public health impact of consuming
      counterfeit cigarettes and the technology used by counterfeiters in the illicit
      cigarette trade. In this study, the concentration of Pb and Cd in twenty-three
      packs of counterfeit cigarettes seized in the US by various law enforcement
      agencies were evaluated and compared with their genuine equivalents using
      microwave digestion followed by inductively coupled plasma - mass spectrometry
      (ICP-MS) analysis. Both Pb and Cd concentration in counterfeit cigarettes were
      markedly higher than those in their genuine equivalents, and exhibited greater
      sample to sample variability. The average Pb and Cd mass fraction values in
      counterfeit cigarettes were (5.13 +/- 2.50) mg/kg (n = 23) and (5.13 +/- 1.95)
      mg/kg (n = 23) respectively, compared with (0.59 +/- 0.08) mg/kg (n = 9) and
      (1.08 +/- 0.08) mg/kg (n = 9) respectively in the genuine equivalents. Results
      suggest that counterfeit cigarettes may impose higher risks to public health.
      Studying these toxic elements could provide important information regarding the
      illicit trade, including the level of organization among counterfeiters, who
      broker between availability of supplies and consumer demand for a cheaper product
      that is assumed to be genuine.

PMID- 25862958
TI  - Quercetin tests negative for genotoxicity in transcriptome analyses of liver and
      small intestine of mice.
AB  - Given the positive results of quercetin in in vitro genotoxicity studies, the in
      vivo genotoxic properties of this important dietary flavonoid warrant testing,
      especially considering possible high intake via widely available food
      supplements. Here, this was done by transcriptome analyses of the most relevant
      tissues, liver and small intestine, of quercetin supplemented mice. Quercetin
      (0.33%) supplemented to a high-fat diet was administered to mice during 12 weeks.
      Serum alanine aminotransferase and aspartate aminotransferase levels revealed no
      indications for hepatotoxicity. Microarray pathway analysis of liver and small
      intestine showed no regulation of genotoxicity related pathways. Analysis of DNA
      damage related genes also did not point at genotoxicity. Furthermore, a published
      classifier set of transcripts for identifying genotoxic compounds did not
      indicate genotoxicity. Only two transcripts of the classifier set were regulated,
      but in the opposite direction compared with the genotoxic compounds 2
      acetylaminofluorene (2-AAF) and aflatoxin B1 (AFB1). Based on the weight of
      evidence of three different types of analysis, we conclude that supplementation
      with quercetin at ~350 mg/kg bw/day for 12 weeks in mice showed no up-regulation
      of genotoxicity related pathways in liver and small intestine.

PMID- 25862956
TI  - Effects of oral exposure to bisphenol A on gene expression and global genomic DNA
      methylation in the prostate, female mammary gland, and uterus of NCTR Sprague
      Dawley rats.
AB  - Bisphenol A (BPA), an industrial chemical used in the manufacture of
      polycarbonate and epoxy resins, binds to the nuclear estrogen receptor with an
      affinity 4-5 orders of magnitude lower than that of estradiol. We reported
      previously that "high BPA" [100,000 and 300,000 ug/kg body weight (bw)/day], but
      not "low BPA" (2.5-2700 ug/kg bw/day), induced clear adverse effects in NCTR
      Sprague-Dawley rats gavaged daily from gestation day 6 through postnatal day
      (PND) 90. The "high BPA" effects partially overlapped those of ethinyl estradiol
      (EE2, 0.5 and 5.0 ug/kg bw/day). To evaluate further the potential of "low BPA"
      to induce biological effects, here we assessed the global genomic DNA methylation
      and gene expression in the prostate and female mammary glands, tissues identified
      previously as potential targets of BPA, and uterus, a sensitive estrogen
      responsive tissue. Both doses of EE2 modulated gene expression, including of
      known estrogen-responsive genes, and PND 4 global gene expression data showed a
      partial overlap of the "high BPA" effects with those of EE2. The "low BPA" doses
      modulated the expression of several genes; however, the absence of a dose
      response reduces the likelihood that these changes were causally linked to the
      treatment. These results are consistent with the toxicity outcomes.

PMID- 25862959
TI  - Antimalarial activity of medicinal plants from the Democratic Republic of Congo:
      A review.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Malaria is the most prevalent parasitic disease
      and the foremost cause of morbidity and mortality in the Democratic Republic of
      Congo. For the management of this disease, a large Congolese population recourses
      to traditional medicinal plants. To date the efficacy and safety of many of these
      plants have been validated scientifically in rodent malaria models. In order to
      generate scientific evidence of traditional remedies used in the Democratic
      Republic of Congo for the management of malaria, and show the potential of
      Congolese plants as a major source of antimalarial drugs, this review highlights
      the antiplasmodial and toxicological properties of the Congolese antimalarial
      plants investigated during the period of 1999-2014. In doing so, a useful
      resource for further complementary investigations is presented. Furthermore, this
      review may pave the way for the research and development of several available and
      affordable antimalarial phytomedicines. MATERIALS AND METHODS: In order to get
      information on the different studies, a Google Scholar and PubMed literature
      search was performed using keywords (malaria, Congolese, medicinal plants,
      antiplasmodial/antimalarial activity, and toxicity). Data from non-indexed
      journals, Master and Doctoral dissertations were also collected. RESULTS:
      Approximately 120 extracts and fractions obtained from Congolese medicinal plants
      showed pronounced or good antiplasmodial activity. A number of compounds with
      interesting antiplasmodial properties were also isolated and identified. Some of
      these compounds constituted new scaffolds for the synthesis of promising
      antimalarial drugs. Interestingly, most of these extracts and compounds possessed
      high selective activity against Plasmodium parasites compared to mammalian cells.
      The efficacy and safety of several plant-derived products was confirmed in mice,
      and a good correlation was observed between in vitro and in vivo antimalarial
      activity. The formulation of several plant-derived products also led to some
      clinical trials and license of three plant-derived drugs (Manalaria((r)),
      Nsansiphos((r)), and Quinine Pharmakina((r))). CONCLUSION: The obtained results
      partly justify and support the use of various medicinal plants to treat malaria
      in folk medicine in the Democratic Republic of Congo. Antimalarial plants used in
      Congolese traditional medicine represent an important source for the discovery
      and development of new antimalarial agents. However, in order to ensure the
      integration of a larger number of plant-derived products in the Congolese
      healthcare system, some parameters and trends should be considered in further
      researches, in agreement with the objectives of the "Traditional Medicine
      Strategy" proposed by the World Health Organization in 2013. These include
      evaluation of geographical and seasonal variation, investigation of reproductive
      biology, assessment of prophylactic antimalarial activity, evaluation of natural
      products as adjuvant antioxidant therapy for malaria, development of plant-based
      combination therapies and monitoring of herbal medicines in pharmacovigilance
      systems.

PMID- 25862960
TI  - Uncovering potential of Indonesian medicinal plants on glucose uptake enhancement
      and lipid suppression in 3T3-L1 adipocytes.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: As obesity is a key factor in the development of
      type 2 diabetes, lowering lipid accumulation in adipose tissues is as important
      as increasing insulin sensitivity in diabetic patients. The selected plant
      extracts used in this screen have been traditionally used in Indonesian medicine
      for the treatment of diabetes and its complications. AIM OF THE STUDY: To
      investigate the ability of the selected plants to both increase insulin
      sensitivity through the enhancement of glucose uptake after insulin induction in
      adipocytes and suppress lipid production in the same target cells. MATERIALS AND
      METHODS: Dried Indonesian medicinal plants were extracted with 50% (v/v) aq.
      methanol. The extracts were dissolved in 50% DMSO when tested in 3T3-L1
      adipocytes. The screening platform consists of insulin-induced glucose uptake,
      lipid accumulation, and cell viability. Initially, an enzymatic fluorescence
      assay was designed to demonstrate the enhancement of 2-deoxyglucose (2-DG) uptake
      after insulin induction. Different concentrations of the extracts that enhanced
      glucose uptake were subjected to lipid accumulation assay using Oil Red O
      staining. Potential extracts based on lipid suppression were subsequently
      assessed by CCK-8 cell viability assay to distinguish lipid reduction activity
      from cytotoxicity. RESULTS: Out of 59 plants, 13 plants demonstrated their
      ability to increase glucose uptake in 3T3-L1 adipocytes after insulin induction,
      and 4 of these plants' extracts suppressed lipid production of the cells. The CCK
      8 assay results of those 4 plant extracts suggest that the lipid inhibition
      activity of Eurycoma longifolia Jack (root) and Piper nigrum L. (fruits) extracts
      is not attributed to their cytotoxicity in the adipose cells. Both of the plant
      extracts increased glucose uptake by more than 200% at 50 MUg/mL and suppressed
      lipid accumulation in a concentration-dependent manner. CONCLUSIONS: Screening of
      selected Indonesian medicinal plants has uncovered the potentials of E.
      longifolia Jack (root) and P. nigrum L. (fruits) with dual active functions,
      increasing insulin sensitivity through the enhancement of glucose uptake and
      reducing lipid accumulation in adipose cells. These findings suggest that the
      ability of both plants to suppress lipid production would provide additional
      benefits in the treatment of diabetes.

PMID- 25862961
TI  - Potent AChE and BChE inhibitors isolated from seeds of Peganum harmala Linn by a
      bioassay-guided fractionation.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Seeds of Peganum harmala Linn are traditionally
      used as folk medical herb in Uighur medicine in China to treat disorders of
      hemiplegia and amnesia. Previously studies have proved that dominating alkaloids
      in P. harmala show significant inhibitory activities on the cholinesterase. AIM
      OF THE STUDY: The aim of the present study is to isolate trace ingredients from
      seeds of P. harmala and evaluate its inhibitory activities on
      acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). MATERIALS AND
      METHODS: For sake of screening effective cholinesterase inhibitors, trace
      compounds were isolated from seeds of P. harmala through a bioassay-guided
      fractionation and their structures were determined via detailed spectral
      analysis. The inhibitory activities on AChE and BChE were assessed using an
      improved Ellman method by UPLC-ESI-MS/MS to determine the common final product
      choline. RESULTS: The activity-guided fractionation led to the isolation of two
      new alkaloids 2-aldehyde-tetrahydroharmine (10), 2-carboxyl-3,4
      dihydroquinazoline (19), one syringin structure analog 1-O-beta-D-xylopyranose
      sinapyl alcohol (22), and along with 19 known compounds. Compounds
      acetylnorharmine (6), harmic acid methy ester (7), harmine N-oxide (13), 6
      methoxyindoline (14), syringin (21) were first found from genus Peganum and
      compounds 3-hydroxylated harmine (4), 1-hydroxy-7-methoxy-beta-carboline (5) were
      new natural products. The results showed that the 2-aldehyde-tetrahydroharmine
      (10) has a potential inbibitive effect on both AChE and BChE with IC50 values of
      12.35 +/- 0.24 and 5.51 +/- 0.33 uM, respectively. Deoxyvasicine (15) and
      vasicine (16) showed the strongest BChE inhibitory activity with IC50 values of
      0.04 +/- 0.01 and 0.1 +/- 0.01 uM. The analysis of the structure-activity
      relationship indicated that the saturation of pyridine ring and the presence of
      substitution at indole ring, C-1, C-3, C-7 and N-2, for beta-carbolines, were
      essential for effective inhibition of both AChE and BChE and the five-membered
      ring between C-2 and N-3 as well as the substituent groups sited at C-4 and C-9,
      for quinazolines, were important to both the AChE/BChE-inhibitory activity.
      CONCLUSIONS: Bioassay-guided fractionation has led to the isolation of AChE and
      BChE inhibitors from the seeds of P. harmala. These results are in agreement with
      the traditional uses of the seeds of P. harmala.

PMID- 25862962
TI  - Oral traditional knowledge on medicinal plants in jeopardy among Gaddi shepherds
      in hills of northwestern Himalaya, J&K, India.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The Gaddi community has been known for its
      shepherd profession from time immemorial. At least one family member or 4-5
      people from a village adopt a nomadic lifestyle with their sheep flocks in
      between the hills of north western Himalaya. In Jammu and Kashmir, India, law
      enforcement has banned the collection of the medicinal plants from the wild
      except for the Gaddi, Gujjar and Bakerwal tribes who are permitted to collect the
      species for their personal use only. As a consequence, knowledge of medicinal
      plants lies with these tribes only. This study has been undertaken to assess the
      status of Oral Traditional Knowledge (OTK) on medicinal plant usage in one of
      these tribes, known as the Gaddi. The study has focused specifically on the Gaddi
      Shepherds as their nomadic lifestyle means that they are closely associated with
      nature and dependent on natural resources for their livelihood including
      treatment of various ailments. MATERIAL AND METHODS: Data on indigenous knowledge
      has been collected through direct interviews of 53 shepherds of the Gaddi tribe
      and analyzed for quantitative parameters such as use-value and factor informant
      consensus. RESULTS: A total of 190 plant species belonging to 70 families,
      growing along the migratory route of the Gaddi Shepherds are used to treat more
      than 80 different ailments and disorders. Leaves are the most common plant parts
      used by the Gaddi Shepherds. The older shepherds are much more aware about the
      traditional knowledge on medicinal plant usage than the younger ones. 56 plant
      species are used to treat a range of gastrointestinal and liver disorders,
      however, diabetic conditions and stings/bites by snakes/scorpions are treated
      using only two plant species each. Mentha longifolia with UV = 0.26 is the
      species most commonly used by the informants for medicinal purposes. The low UV
      (below 1) and low Fic (near 0) is a common observation in the present study.
      CONCLUSIONS: The UV and Fic, analysis reveals that OTK on the medicinal plants is
      dwindling among the Gaddi Shepherds in Jammu and Kashmir, India.

PMID- 25862963
TI  - Cholesterol lowering effect in the gall bladder of dogs by a standardized
      infusion of Herniaria hirsuta L.
AB  - ETNOPHARMACOLOGICAL RELEVANCE: Infusions of Herniaria hirsuta L., Herniaria
      glabra L. and Herniaria fontanesii J.Gay are well known in Moroccon folk medicine
      for the treatment of biliary dyskinesia, (uro)lithiasis or as a diuretic.
      Herniariae Herba which can contain H. glabra and H. hirsuta is known in Europe as
      an urological drug. AIM OF THE STUDY: To investigate the efficacy of a
      standardized infusion of Herniaria hirsuta against choleltihiasis, and evaluation
      of its genotoxicity. METHODS AND MATERIALS: An analytical HPLC-UV method to
      quantify flavonoids and saponins present in the extract of H. hirsuta was
      developed and validated. An in vivo experiment to evaluate the cholesterol
      lowering effect of a infusion of H. hirsuta in the gall bladder of dogs was
      carried out. Dogs were divided into 3 groups i.e. control dogs (CG), dogs treated
      with ursodeoxycholic acid (UDCA) (2*7.35mg/kg body weight/day) and dogs treated
      with the standardized infusion (HG) (2*48.5mg/kg body weight/day). Dogs were fed
      a fatty diet during 120 days after which a diet without additional fat was
      introduced till day 180. Treatment started 30 days after introduction of the
      fatty diet and lasted till the end of the experiment. A bile and blood sample of
      each dog was collected every 30 days, after which the concentration of
      cholesterol was determined. An Ames test was performed according to the OECD
      guidelines. RESULTS: The validated HPLC-UV method showed a linear calibration
      model and an acceptable precision for the total flavonoid content (total content
      4.51%) as well as the total saponin content (12.74%). The in vivo experiments
      already showed a minor difference for bile cholesterol between CG and HG after 30
      days of treatment with the infusion, and the difference was more pronounced after
      90 days of treatment. Even 30 days after discontinuation of the cholesterol-rich
      diet a significant difference remained between CG and HG. There was no
      statistically significant difference in blood cholesterol. The Ames test showed
      that the infusion of H. hirsuta could be considered as being free from genotoxic
      risks. CONCLUSION: A method for the standardization of a infusion of Herniaria
      hirsuta was developed and validated. Prolonged use of this standardized H.
      hirsuta extract resulted in a cholesterol-lowering effect in the bile of dogs.
      Since this pharmacological effect prevents the formation of gallstones and can
      contribute to solving existing gallstones, a standardized infusion of H. hirsuta
      may have a positive effect in the treatment of gallstones in human patients.

PMID- 25862964
TI  - Medicinal plants used for musculoskeletal disorders in Navarra and their
      pharmacological validation.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: This paper provides important
      ethnopharmacological information on plants used in musculoskeletal disorders in
      Navarra. MATERIAL AND METHODS: Information was collected using semi-structured
      ethnobotanical interviews. In order to confirm the pharmacological validation of
      the uses, monographs from Official International Agencies (ESCOP, Commission E,
      WHO and EMA) were reviewed. A literature review was conducted focusing on the
      plants that were widely used but had no published monograph. RESULTS: A total of
      199 pharmaceutical uses were reported, for 38 plants and 24 families, mainly
      represented by Asteraceae and Lamiaceae (11%, each), Rosaceae (8%) and
      Boraginaceae, Cucurbitaceae, Equisetaceae, Malvaceae, Oleaceae and Urticaceae
      (5%, each). The most frequently used parts were the aerial parts, roots, followed
      by inflorescences and leaves. Nine out of 38 plants (24%) and 123 uses (62%), had
      already been pharmacologically validated. CONCLUSIONS: The authors propose to
      validate four species for their use in musculoskeletal disorders: Verbena
      officinalis, Symphytum tuberosum, Hypericum perforatum and Equisetum ssp.

PMID- 25862965
TI  - Pre-clinical evidences of Pyrostegia venusta in the treatment of vitiligo.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Leaves of Pyrostegia venusta are popularly used
      to treat vitiligo; however, none in vivo study showed its ability. AIM OF THE
      STUDY: The overall objective of the present study was to evaluate the
      antiinflammatory and hyperpigmentant activities of hydroethanolic (HE) extract of
      leaves from P. venusta in animal models of vitiligo induced by croton oil and
      monobenzone. MATERIALS AND METHODS: The antiinflamatory and antioxidative effects
      of topical and oral administration of HE extract of P. venusta were evaluated in
      Swiss mice on edema model induced by croton oil, and further the N-acetyl-b-d
      glucosaminidase (NAG) activity, cell infiltration, and cytokine and reactive
      species oxygen (ROS) levels. The involvement on mice pigmentation, cell
      infiltration and cytokine levels were evaluated on vitiligo model induced by
      monobenzone in C56BL/6 mice. RESULTS: HE of P. venusta by gavage (300 mg/kg)
      reduced NAG activity in 32.5 +/- 5% on mouse ear edema induced by croton oil.
      Similarly, cell infiltration was lower (42.3 +/- 5.9%) when compared to control
      group, as well as interleukin-1beta (IL-1beta), interleukin (IL-6) and tumor
      necrosis factor-alpha (TNF-alpha) levels, in 44.1 +/- 9.7%, 71.9 +/- 22.2% and to
      basal levels, respectively. Topical treatment with HE of P. venusta (10%)
      diminished cell infiltration (67.7 +/- 7.1%) and ROS levels (total reduction). P.
      venusta either by gavage (300 mg/Kg) or topically (10%) increased epidermal
      melanin level (116.5 +/- 13% and 100 +/- 16.9%, respectively), diminished dermal
      depigmentation (36.0 +/- 6.7% and 38.2 +/- 6.2%, respectively), as well as tissue
      TNF-alpha levels (68.2 +/- 11.6% and 99.2 +/- 12.1%, respectively) and cell
      infiltration (basal levels and 94.3 +/- 9.17%, respectively). However, only
      topical treatment with HE of P. venusta altered melanin specific marker in hair
      follicles. CONCLUSIONS: For the first time these data show that topical and oral
      administrations of P. venusta have significant antiinflammatory and
      hyperpigmentant effects, demonstrating different topical and systemic effects
      through two animal models. Together these models are capable to mimic several
      features founded in vitiligo, and the results support the ethnopharmacological
      use of P. venusta.

PMID- 25862966
TI  - Selective modulation of MAPKs contribute to the anti-proliferative and anti
      inflammatory activities of 1,7-dihydroxy-3,4-dimethoxyxanthone in rheumatoid
      arthritis-derived fibroblast-like synoviocyte MH7A cells.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: 1,7-Dihydroxy-3,4-dimethoxyxanthone (XAN) is an
      antirheumatic agent isolated from traditional Chinese medicine Securidaca
      inappendiculata Hassk. This study was designed to investigate its anti
      proliferative and anti-inflammatory activities on rheumatoid arthritis derived
      fibroblast-like synoviocyte cell line MH7A, and explore the underlying mechanism
      of action. METHODS: The anti-proliferative activity of XAN on MH7A cells was
      assessed by an MTT method. Its pro-apoptotic and cell cycle arrest activities
      were analyzed by flow cytometry. W-B method was employed to investigate hallmark
      kinases involved in the course. Pro-inflammatory cytokines in culture supernatant
      of MH7A cells were determined by an ELISA method. RESULTS: The results showed XAN
      efficiently suppressed the proliferation and secretion of IL-1beta and IL-6 of
      MH7A cells in a concentration-dependent manner. Co-treatment with MAPKs
      inhibitors U0126, SB202190 and SP600125 indicated JNK and p38 pathways were
      involved in the course. Up-regulation of p-p38, p-ERK, bax and p21, and down
      regulation of p-JNK, cyclin D1 and bcl-2 were observed upon the treatment with
      XAN. SB202190 partly reversed the modulatory effects. The results suggested XAN
      inhibited the proliferation of MH7A cells mainly via cell cycle arrest at G1/S
      phase, and the activity was due to the up-regulation of p-p38, which led to the
      modulation of p21 and cyclin D1. The down-regulation of p-JNK by XAN suppressed
      the secretion of pro-inflammatory cytokines, which was beneficial to the anti
      proliferative activity of MH7A cells. CONCLUSION: XAN selectively modulated MAPKs
      signaling, and exerted the subsequent anti-proliferative and anti-inflammatory
      activities on MH7A cells.

PMID- 25862967
TI  - The resveratrol oligomers, cis- and trans-gnetin H, from Paeonia suffruticosa
      seeds inhibit the growth of several human cancer cell lines.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Paeonia suffruticosa Andrews (PSE) is a well
      known Chinese medicine that has been widely used as an anti-tumor, anti-oxidative
      and anti-inflammatory agent. cis- and trans-gnetin H are two resveratrol
      oligomers isolated from the seeds of PSE. Although resveratrol is widely
      considered to be one of the most valuable natural chemopreventive agents and
      there are numerous studies on the antitumor activities of resveratrol, little is
      known about the antitumor properties of cis- and trans-gnetin H. MATERIALS AND
      METHODS: The inhibitory effects of cis- and trans-gnetin H in different human
      cancer cell lines were assessed using fluorescent viability tests. Cytotoxicity
      in human lung and breast cancer cells was detected via nuclear condensation, cell
      permeability, and changes in the mitochondrial membrane potential (?psim).
      Apoptosis in human lung and breast cancer cells was assessed by flow cytometry, a
      luminescence assay and high-content screening analysis. Finally, a xenograft mice
      model was used to examine the efficacy of cis-gnetin H on lung tumors. RESULTS:
      cis- and trans-gnetin H have superior activity in inhibiting the proliferation of
      four human cancer cell lines, A549 (lung), BT20 (breast), MCF-7 (breast) and U2OS
      (osteosarcoma), and promote cell apoptosis, while having a minimal effect on two
      normal human epithelial cell lines, HPL1A (lung) and HMEC (breast) used as
      controls. cis- and trans-gnetin H promote apoptosis by releasing mitochondria
      cytochrome c, activating caspase 3/7 and inhibiting NF-kappaB activation. Flow
      cytometry analysis shows that cis- or trans-gnetin H arrested the cell cycle of
      cancer cells at the G0-G1 phase. Moreover, cis-gnetin H suppressed the growth of
      xenograft lung tumors in mice. CONCLUSION: Collectively, our findings demonstrate
      the promise of the natural compounds cis- and trans-gnetin H as candidates for
      cancer chemotherapy agents.

PMID- 25862968
TI  - Effects of Schisandra chinensis extract on gastrointestinal motility in mice.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Schisandra chinensis (Turcz.) Baill. (SC)
      continues to be used as a traditional folk medicine in Asia, especially for the
      treatment of gastrointestinal (GI) disorders related to gastritis, diarrhea,
      enterocolitis and abnormal GI motility. AIM OF THE STUDY: Because GI disorders,
      especially abnormal GI motility, are major lifelong problems, we investigated the
      effects of SC on the pacemaker activity of the interstitial cells of Cajal (ICCs)
      in murine small intestine and GI motility. MATERIALS AND METHODS: Enzymatic
      digestions were used to dissociate ICCs from small intestines, and the whole-cell
      patch-clamp configuration was used to record potentials generated by cultured
      ICCs. In vivo effects of SC on GI motility were investigated by measuring the
      intestinal transit rate (ITR) of Evans blue in normal and GI motility dysfunction
      mice. RESULTS: SC extracts depolarized the membrane potentials of ICCs in a dose
      dependent manner. Pretreatment with Ca(2+) free solution or thapsigargin (a
      Ca(2+)-ATPase inhibitor in the endoplasmic reticulum) abolished the generation of
      pacemaker potentials by ICCs, and under these conditions, SC extract did not
      depolarize the membrane potentials of ICCs. In addition, membrane depolarizations
      were inhibited by intracellular GDPbetaS and by U-73122 (an active phospholipase
      C (PLC) inhibitor). In normal mice, ITRs were significantly increased by SC
      extract (0.1-1g/kg, intragastrically (i.g.)) in a dose dependent manner. Also, SC
      extract significantly recovered the GI motility dysfunctions in acetic acid (AA)
      injected and streptozotocin (STZ)-induced diabetic mice, which are the GI
      motility animal models. MATERIALS AND METHODS: SC extract modulates pacemaker
      potentials in ICCs in a dose dependent manner via external and internal Ca(2+)
      regulations, and via G protein and the PLC pathway. In addition, SC extract
      increased ITRs in normal and abnormal GI motility mice models. This study shows
      that SC extract offers a basis for the development of a prokinetic agent that
      prevents or alleviates GI motility dysfunctions.

PMID- 25862969
TI  - Multi-parametric analysis of phagocyte antimicrobial responses using imaging flow
      cytometry.
AB  - We feature a multi-parametric approach based on an imaging flow cytometry
      platform for examining phagocyte antimicrobial responses against the gram
      negative bacterium Aeromonas veronii. This pathogen is known to induce strong
      inflammatory responses across a broad range of animal species, including humans.
      We examined the contribution of A. veronii to the induction of early phagocyte
      inflammatory processes in RAW 264.7 murine macrophages in vitro. We found that A.
      veronii, both in live or heat-killed forms, induced similar levels of macrophage
      activation based on NF-kappaB translocation. Although these macrophages
      maintained high levels of viability following heat-killed or live challenges with
      A. veronii, we identified inhibition of macrophage proliferation as early as 1h
      post in vitro challenge. The characterization of phagocytic responses showed a
      time-dependent increase in phagocytosis upon A. veronii challenge, which was
      paired with a robust induction of intracellular respiratory burst responses.
      Interestingly, despite the overall increase in the production of reactive oxygen
      species (ROS) among RAW 264.7 macrophages, we found a significant reduction in
      the production of ROS among the macrophage subset that had bound A. veronii.
      Phagocytic uptake of the pathogen further decreased ROS production levels, even
      beyond those of unstimulated controls. Overall, this multi-parametric imaging
      flow cytometry-based approach allowed for segregation of unique phagocyte sub
      populations and examination of their downstream antimicrobial responses, and
      should contribute to improved understanding of phagocyte responses against
      Aeromonas and other pathogens. 

PMID- 25862970
TI  - Identification of regulators of the early stage of viral hemorrhagic septicemia
      virus infection during curcumin treatment.
AB  - The effect of curcumin pretreatment (15-240 MUM) in fathead minnow cells infected
      with viral hemorrhagic septicemia virus (VHSV) was evaluated. Cell viability,
      apoptosis and viral copy number were analyzed using Cell Counting Kit-8 assay,
      Annexin V staining, and reverse transcription-PCR, respectively. Pretreatment
      with 120 MUM curcumin showed an increase in viability (>90% of mock) of VHSV
      infected cells and reduction in the copy number (0.2-log reduction in VHSV N gene
      expression), reactive oxygen species and apoptosis in the cells without cytotoxic
      effects. To understand the mechanisms underlaying the antiviral effects of
      curcumin pretreatment, a comparative proteomic analysis was performed in four
      samples (M, mock; C, curcumin-treated; V, VHSV-infected; and CV, curcumin-treated
      VHSV-infected) in triplicate. In total, 185 proteins were detected. The analysis
      showed that three proteins, including heat shock cognate 71 (HSC71), actin, alpha
      cardiac muscle (ACTC1) and elongation factor 1 (EEF1) were differentially
      expressed between V and CV samples. Network analysis performed by Ingenuity
      Pathways Analysis (IPA) showed that HSC71 was the primary protein interacting
      with fibronectin (FN) 1, actins (ACTB, ACTG, F-actin) and gelsolin (GSN) in both
      V and CV samples and thus is a strong target candidate for the protection from
      VHSV infection at the viral entry stage. Our proteomics data suggest that
      curcumin pretreatment inhibits entry of VHSV in cells by downregulating FN1 or
      upregulating F-actin. For both proteins, HSC71 acts as a binding protein that
      modulates their functions. Furthermore, consistent with the effect of a heat
      shock protein inhibitor (KNK437), curcumin downregulated HSC71 expression with
      increasing viability of VHSV-infected cells and inhibited VHSV replication,
      suggesting that the downregulation of HSC71 could be responsible for the
      antiviral activity of curcumin. In conclusion, this study indicates that the
      suppression of viral entry by rearrangement of the F-actin/G-actin ratio via
      downregulating HSC71 is a plausible mechanism by which curcumin pretreatment
      controls the early stages of VHSV infection.

PMID- 25862971
TI  - Effect of a new recombinant Aeromonas hydrophila vaccine on the grass carp
      intestinal microbiota and correlations with immunological responses.
AB  - Intestinal microbiota has become an integral component of the fish, and plays a
      key role in host metabolism, immunity and health maintenance. However,
      information on the immune responses after vaccine administration in relation to
      the intestinal microbiota is absent in fish. The present study focused on the
      effect of a new recombinant Aeromonas hydrophila vaccine (Aera) by using a novel
      functionalized, single-walled carbon nanotubes (SWCNTs) as a delivery vehicle on
      the intestinal microbiota of grass carp (Ctenopharyngodon idella) through the
      bath immunization, and further explored the immunological responses in intestine,
      kidney and spleen. By performing deep sequencing, a total of 81,979 valid reads
      and 609 OTUs obtained from 4 intestine samples were analyzed. We detected 141
      genuses, most of which belonged to Firmicutes, Fusobacteria and Proteobacteria.
      Of note, the quantity of Aeromonas in library Aera (after 6 h Aera vaccine
      pretreatment, fish were transferred to tanks without SWCNTs-Aera for 28 d) and
      Aera-GD (6 h Aera vaccine pretreated prior to the group injected by A.
      hydrophila) was declined 6.5% and 14.6% compared with the control, respectively.
      Moreover, the expression of seven immune-related genes (IFN-I, TNF-alpha, CRP, IL
      8, IgM, MHC I and CD8alpha) in the intestine, kidney and spleen of Aera treated
      fish was significantly enhanced, which indicated that a better tissue immune
      response in grass carp was induced by the SWCNTs-Aera vaccine. Therefore, a new
      recombinant SWCNT-Aera vaccine may represent potentially efficient and
      immunological role in grass carp intestine to resist A. hydrophila infection.

PMID- 25862972
TI  - The complexity of apoptotic cell death in mollusks: An update.
AB  - Apoptosis is a type of programmed cell death that produces changes in cell
      morphology and in biochemical intracellular processes without inflammatory
      reactions. The components of the apoptotic pathways are conserved throughout
      evolution. Caspases are key molecules involved in the transduction of the death
      signal and are responsible for many of the biochemical and morphological changes
      associated with apoptosis. Nowadays, It is known that caspases are activated
      through two major apoptotic pathways (the extrinsic or death receptor pathway and
      the intrinsic or mitochondrial pathway), but there are also evidences of at least
      other alternative pathway (the perforin/granzyme pathway). Apoptosis in mollusks
      seems to be similar in complexity to apoptosis in vertebrates but also has unique
      features maybe related to their recurrent exposure to environmental changes,
      pollutants, pathogens and also related to the sedentary nature of some stages in
      the life cycle of mollusks bivalves and gastropods. As in other animals,
      apoptotic process is involved in the maintenance of tissue homeostasis and also
      constitutes an important immune response that can be triggered by a variety of
      stimuli, including cytokines, hormones, toxic insults, viruses, and protozoan
      parasites. The main goal of this work is to present the current knowledge of the
      molecular mechanisms of apoptosis in mollusks and to highlight those steps that
      need further study. 

PMID- 25862973
TI  - Molecular cloning and expression analysis of an apoptosis-associated gene Daxx
      from zebrafish, Danio rerio.
AB  - The death domain-associated protein Daxx exerts many functions including the
      induction and inhibition of apoptosis, regulation of chromatin remodeling and
      gene transcription. In this report, we have cloned and characterized a Daxx
      ortholog from the zebrafish, Danio rerio. The bioinformatics analysis results
      indicated that the open reading frame (ORF) of zebrafish Daxx is 2,151bp long and
      encodes a putative protein of 716 amino acids containing Daxx domain. Though
      quantitative PCR analyses, Daxx mRNA was detected in embryonic development from 6
      h to 120 h and in all 11 selected zebrafish tissues, and the expression of Daxx
      was increased first and then decreased during megalocytivirus infectious spleen
      and kidney necrosis virus (ISKNV) infection. Fluorescence microscopy indicated
      that the full-length protein was located in the nuclei of the tested Hela cells
      uniformly but punctiform distribution in HEK293T. In the luciferase report
      assays, the GAL4-Daxx fusion protein inhibited the transcriptional activity of
      L8G5-Luc reporter gene showed that Daxx might act as a transcriptional repressor,
      following the over-expression in HEK293T, the activation of NF-kappaB-Luc and
      p53/p21-Luc reporter genes were repressed by the protein. These results suggested
      that Daxx might play definite role in apoptosis and innate immunity in zebrafish.

PMID- 25862974
TI  - Patterns of Piscirickettsia salmonis load in susceptible and resistant families
      of Salmo salar.
AB  - The pathogen Piscirickettsia salmonis produces a systemic aggressive infection
      that involves several organs and tissues in salmonids. In spite of the great
      economic losses caused by this pathogen in the Atlantic salmon (Salmo salar)
      industry, very little is known about the resistance mechanisms of the host to
      this pathogen. In this paper, for the first time, we aimed to identify the
      bacterial load in head kidney and muscle of Atlantic salmon exhibiting
      differential familiar mortality. Furthermore, in order to assess the patterns of
      gene expression of immune related genes in susceptible and resistant families, a
      set of candidate genes was evaluated using deep sequencing of the transcriptome.
      The results showed that the bacterial load was significantly lower in resistant
      fish, when compared with the susceptible individuals. Based on the candidate
      genes analysis, we infer that the resistant hosts triggered up-regulation of
      specific genes (such as for example the LysC), which may explain a decrease in
      the bacterial load in head kidney, while the susceptible fish presented an
      exacerbated innate response, which is unable to exert an effective response
      against the bacteria. Interestingly, we found a higher bacterial load in muscle
      when compared with head kidney. We argue that this is possible due to the
      availability of an additional source of iron in muscle. Besides, the results show
      that the resistant fish could not be a likely reservoir of the bacteria. 

PMID- 25862975
TI  - Extracellular DNA in oral microbial biofilms.
AB  - The extracellular matrix of microbial biofilms is critical for surface adhesion
      and nutrient homeostasis. Evidence is accumulating that extracellular DNA plays a
      number of important roles in biofilm integrity and formation on hard and soft
      tissues in the oral cavity. Here, we summarise recent developments in the field
      and consider the potential of targeting DNA for oral biofilm control. 

PMID- 25862976
TI  - Molecular characterization of 7 new established cell lines from high grade serous
      ovarian cancer.
AB  - Cancer cell lines are good in vitro models to study molecular mechanisms
      underlying chemoresistance and cancer recurrence. Recent works have demonstrated
      that most of the available ovarian cancer cell lines are most unlikely high grade
      serous (HGSOC), the major type of epithelial ovarian cancer. We aimed at
      establishing well characterized HGSOC cell lines, which can be used as optimal
      models for ovarian cancer research. We successfully established seven cell lines
      from HGSOC and provided the major genomic alterations and the transcriptomic
      landscapes of them. They exhibited different gene expression patterns in the key
      pathways involved in cancer resistance. Each cell line harbored a unique TP53
      mutation as their corresponding tumors and expressed cytokeratins 8/18/19 and
      EpCAM. Two matched lines were established from the same patient, one at diagnosis
      and being sensitive to carboplatin and the other during chemotherapy and being
      resistant. Two cell lines presented respective BRCA1 and BRCA2 mutations. To
      conclude, we have established seven cell lines and well characterized them at
      genomic and transcriptomic levels. They are optimal models to investigate the
      molecular mechanisms underlying the progression, chemo resistance and recurrence
      of HGSOC. 

PMID- 25862978
TI  - iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated
      proteins in a rat chronic mild stress model of depression.
AB  - Major depressive disorder (MDD) is a prevalent psychiatric mood illness and a
      major cause of disability and suicide worldwide. However, the underlying
      pathophysiology of MDD remains poorly understood due to its heterogenic nature.
      Extensive pre-clinical research suggests that many molecular alterations
      associated with MDD preferentially localize to the postsynaptic density (PSD).
      Here, we used a rodent chronic mild stress (CMS) model to generate susceptible
      and unsusceptible subpopulations. Proteomic analysis using an isobaric tag for
      relative and absolute quantitation (iTRAQ) and tandem mass spectrometry was
      performed to identify differentially expressed proteins in enriched PSD
      preparations from the hippocampi of different groups. More than 1500 proteins
      were identified and quantified, and 74 membrane proteins were differentially
      expressed. Of these membrane proteins, 51 (69%) were identified by SynaptomeDB
      search as having a predicted PSD localization. The unbiased profiles identified
      several PSD candidate proteins that may be related to CMS vulnerability or
      insusceptibility, and these two CMS phenotypes displayed differences in the
      abundance of several types of proteins. A detailed protein functional analysis
      pointed to a role for PSD-associated proteins involved in signaling and
      regulatory functions. Within the PSD, the N-methyl-D-aspartate (NMDA) receptor
      subunit NR2A and its downstream targets contribute to CMS susceptibility. Further
      analysis of disease relevance indicated that the PSD contains a complex set of
      proteins of known relevance to mental illnesses including depression. In sum,
      these findings provide novel insights into the contribution of PSD-associated
      proteins to stress susceptibility and further advance our understanding of the
      role of hippocampal synaptic plasticity in MDD.

PMID- 25862977
TI  - The secretory pathway kinases.
AB  - Protein phosphorylation is a nearly universal post-translation modification
      involved in a plethora of cellular events. Even though phosphorylation of
      extracellular proteins had been observed, the identity of the kinases that
      phosphorylate secreted proteins remained a mystery until only recently. Advances
      in genome sequencing and genetic studies have paved the way for the discovery of
      a new class of kinases that localize within the endoplasmic reticulum, Golgi
      apparatus and the extracellular space. These novel kinases phosphorylate proteins
      and proteoglycans in the secretory pathway and appear to regulate various
      extracellular processes. Mutations in these kinases cause human disease, thus
      underscoring the biological importance of phosphorylation within the secretory
      pathway. This article is part of a Special Issue entitled: Inhibitors of Protein
      Kinases. 

PMID- 25862979
TI  - Human contact imagined during the production process increases food naturalness
      perceptions.
AB  - It is well established that food processing and naturalness are not good friends,
      but is food processing always detrimental to naturalness? Building on the
      contagion principle, this research examines how production mode (handmade vs.
      machine-made) influences naturalness perceptions. In a pilot study (n = 69) and
      an experiment (n = 133), we found that compared with both a baseline condition
      and a condition in which the mode of production process was portrayed as machine
      made, a handmade production mode increases naturalness ratings of a grape juice.
      A mediation analysis demonstrates that these effects result from higher perceived
      human contact suggesting that the production process may preserve food
      naturalness when humanized. 

PMID- 25862981
TI  - Bringing comfort and convenience to the colonial table: Delhaize Freres & Cie's
      Colonial Department in the 1920s and 1930s.
AB  - The paper explores the role of convenient shopping in establishing a sense of
      comfort for Europeans in a colonial environment. So far, there has been little
      investigation into how Belgian retailers tried to gain a firm foothold in the
      Congo, how they presented themselves and promoted their wares. This paper
      examines the activities of the colonial department of Delhaize Freres & Cie 'Le
      Lion', Belgium's first and largest food multiple. It examines how this large
      grocery chain tried to establish itself in the Congo, what motivations it had to
      extend its business to the colony, what audience it wished to reach, what
      products and services it had to offer and what sales and marketing strategies
      were used. It appears that convenient shopping was one of the key selling points
      Delhaize's advertising, while also characterising its products as indispensable
      for Europeans' comfort, moral respectability and homely warmth in a so-called
      primitive, backward environment. 

PMID- 25862980
TI  - Brain and behavioral perturbations in rats following Western diet access.
AB  - Energy dense "Western" diets (WD) are known to cause obesity as well as learning
      and memory impairments, blood-brain barrier damage, and psychological
      disturbances. Impaired glucose (GLUT1) and monocarboxylate (MCT1) transport may
      play a role in diet-induced dementia development. In contrast, ketogenic diets
      (KD) have been shown to be neuroprotective. We assessed the effect of 10, 40 and
      90 days WD, KD and Chow maintenance on spontaneous alternation (SA) and vicarious
      trial and error (VTE) behaviors in male rats, then analyzed blood glucose,
      insulin, and ketone levels; and hippocampal GLUT1 and MCT1 mRNA. Compared to Chow
      and KD, rats fed WD had increased 90 day insulin levels. SA was decreased in WD
      rats at 10, but not 40 or 90 days. VTE was perturbed in WD-fed rats, particularly
      at 10 and 90 days, indicating hippocampal deficits. WD rats had lower hippocampal
      GLUT1 and MCT1 expression compared to Chow and KD, and KD rats had increased 90
      day MCT1 expression compared to Chow and WD. These data suggest that WD reduces
      glucose and monocarboxylate transport at the hippocampus, which may result in
      learning and memory deficits. Further, KD consumption may be useful for MCT1
      transporter recovery, which may benefit cognition. 

PMID- 25862982
TI  - Attentional biases towards familiar and unfamiliar foods in children. The role of
      food neophobia.
AB  - Familiarity of food stimuli is one factor that has been proposed to explain food
      preferences and food neophobia in children, with some research suggesting that
      food neophobia (and familiarity) is at first a predominant of the visual domain.
      Considering visual attentional biases are a key factor implicated in a majority
      of fear-related phobias/anxieties, the purpose of this research was to
      investigate attentional biases to familiar and unfamiliar fruit and vegetables in
      8 to 11 year old children with differing levels of food neophobia. To this end,
      70 primary aged children completed a visual-probe task measuring attentional
      biases towards familiar and unfamiliar fruit/vegetables, as well as the food
      neophobia, general neophobia and willingness to try self-report measures. Results
      revealed that as an undifferentiated population all children appeared to
      demonstrate an attentional bias towards the unfamiliar fruit and vegetable
      stimuli. However, when considering food neophobia, this bias was significantly
      exaggerated for children self-reporting high food neophobia and negligible for
      children self-reporting low food neophobia. In addition, willingness to try the
      food stimuli was inversely correlated with attentional bias towards the
      unfamiliar fruits/vegetables. Our results demonstrate that visual aspects of food
      stimuli (e.g. familiarity) play an important role in childhood food neophobia.
      This study provides the first empirical test of recent theory/models of food
      neophobia (e.g. Brown & Harris, 2012). Findings are discussed in light of these
      models and related anxiety models, along with implications concerning the
      treatment of childhood food neophobia. 

PMID- 25862983
TI  - Parental control over feeding in infancy. Influence of infant weight, appetite
      and feeding method.
AB  - BACKGROUND AND OBJECTIVE: Parental control over feeding has been linked to child
      overweight. Parental control behaviours have been assumed to be exogenous to the
      child, but emerging evidence suggests they are also child-responsive. This study
      tests the hypothesis that parental control in early infancy is responsive to
      infant appetite and weight. SUBJECTS AND METHODS: Participants were 1920 mothers
      from the Gemini twin cohort, using one randomly selected child per family. Data
      come from questionnaires completed when the children were approximately 8 months.
      Mothers completed measures of 'pressure' and 'restriction', reported feeding
      method (breast- and bottle feeding), rated their infant's appetite during the
      first 3 months, provided health professional recorded weight measurements, and
      reported their concerns about their infant's weight. Logistic regression examined
      predictors of 'pressure' and 'restriction', adjusting for maternal demographics
      and BMI. Interactions between feeding method and control were also tested.
      RESULTS: 'Pressure' was associated with lower birth weight (OR = 0.79, 95% CI:
      0.65-0.97), greater concern about underweight (OR = 1.88, 1.29-2.75), and lower
      infant appetite (OR = 0.59, 0.47-0.75). 'Restriction' was associated with higher
      appetite (OR = 1.44, 1.09-1.89) and bottle feeding (OR = 2.86, 2.18-3.75). A
      significant interaction with feeding method indicated that infants with high
      appetites were more likely to be restricted only if they were bottle-fed (OR =
      1.52, 1.13-2.04). CONCLUSION: Mothers vary in their levels of control over milk
      feeding and this is partly responsive to the infant's characteristics. They tend
      to pressure infants who are lighter and have a smaller appetite, and restrict
      infants with larger appetites if they are bottle-fed. Guidance on infant feeding
      may be better received if it acknowledges that parents respond to infant
      characteristics in order to achieve their feeding goals.

PMID- 25862984
TI  - Oxidative stress and Treg depletion in lupus patients with anti-phospholipid
      syndrome.
AB  - Anti-phospholipid antibodies (APLA) represent a diagnostic criterion of systemic
      lupus erythematosus (SLE) and cause morbidity, termed anti-phospholipid syndrome
      (APS). Activation of the mechanistic target of rapamycin (mTOR) has been recently
      associated with APS. mTOR is a sensor of oxidative stress. Therefore, we examined
      mitochondrial mass, superoxide production, mTOR activity and FoxP3 expression in
      72 SLE patients, twelve of whom also had APS, and 54 healthy controls by flow
      cytometry. Mitochondrial mass was increased in CD4(-)CD8(-) double-negative (DN)
      T cells of SLE patients with APS (2.7-fold) in comparison to those without APS
      (1.7-fold; p = 0.014). Superoxide production was increased in all lymphocyte
      subsets of APS patients. FoxP3(+) cells were depleted within CD4(+)CD25(+) Tregs
      in patients with APS (28.4%) relative to those without APS (46.3%, p = 0.008).
      mTOR activity was similar between SLE patients with and without APS. Thus,
      oxidative stress and Treg depletion rather than mTOR activation underlie APS in
      patients with SLE.

PMID- 25862985
TI  - Rapid Resolution of Hepatitis C Virus-Associated Cryoglobulin Rash With Use of
      Direct-Acting Antivirals.

PMID- 25862986
TI  - It Is Time to Treat to Trough: Staying Ahead of the Curve in Biologic Testing.

PMID- 25862987
TI  - Persistent or Recurrent Anemia Is Associated With Severe and Disabling
      Inflammatory Bowel Disease.
AB  - BACKGROUND & AIMS: Anemia is a common manifestation of inflammatory bowel disease
      (IBD) that can greatly affect patients' quality of life. We performed a
      prospective study of a large cohort of patients with IBD to determine if patterns
      of anemia over time are associated with aggressive or disabling disease. METHODS:
      We performed a longitudinal analysis of demographic, clinical, laboratory, and
      treatment data from a registry of patients with IBD at the University of
      Pittsburgh Medical Center from 2009 through 2013. Patients with a complete follow
      up evaluation (at least 1 annual visit with laboratory results) were included.
      Anemia was defined by World Health Organization criteria. Disease activity scores
      (the Harvey-Bradshaw Index or the ulcerative colitis activity index) and quality
      of-life scores (based on the short IBD questionnaire) were determined at each
      visit; laboratory data, including levels of C-reactive protein and erythrocyte
      sedimentation rates, as well as patterns of IBD-related health care use, were
      analyzed. RESULTS: A total of 410 IBD patients (245 with Crohn's disease, 165
      with ulcerative colitis; 50.5% female) were included. The prevalence of anemia in
      patients with IBD was 37.1% in 2009 and 33.2% in 2013. Patients with IBD and
      anemia required significantly more health care and had higher indices of disease
      activity, as well as a lower average quality of life, than patients without
      anemia (P < .0001). Anemia (persistent or recurrent) for 3 or more years was
      correlated independently with hospitalizations (P < .01), visits to
      gastroenterology clinics (P < .001), telephone calls (P < .004), surgeries for
      IBD (P = .01), higher levels of C-reactive protein (in patients with ulcerative
      colitis, P = .001), and a higher erythrocyte sedimentation rate (P < .0001).
      Anemia was correlated negatively with quality-of-life scores (P < .03).
      CONCLUSIONS: Based on a longitudinal analysis of 410 patients, persistent or
      recurrent anemia correlates with more aggressive or disabling disease in patients
      with IBD.

PMID- 25862988
TI  - Trends in Hospitalization for Diverticulitis and Diverticular Bleeding in the
      United States From 2000 to 2010.
AB  - BACKGROUND & AIMS: Most studies of trends in diverticular disease have focused on
      diverticulitis or on a composite outcome of diverticulitis and bleeding. We aimed
      to quantify and compare the prevalence of hospitalization for diverticular
      bleeding and diverticulitis overall and by sex and race. METHODS: We analyzed
      data from the Nationwide Inpatient Sample from 2000 through 2010. We identified
      adult patients with a discharge diagnosis of diverticular bleeding or
      diverticulitis. By using yearly US intercensal data, we calculated age-, sex-,
      and race-specific rates, as well as age-adjusted prevalence rates. RESULTS: The
      prevalence of hospitalizations per 100,000 persons for diverticular bleeding
      decreased over the 10-year period from 32.5 to 27.1 (-5.4; 95% confidence
      interval, -5.1 to -5.7). The prevalence of hospitalizations for diverticulitis
      peaked in 2008 (74.1/100,000 in 2000, 96.0/100,000 in 2008, and 91.9/100,000 in
      2010). The prevalence of diverticulitis was higher in women than in men, whereas
      women and men had similar rates of diverticular bleeding. The prevalence of
      diverticular bleeding was highest in blacks (34.4/100,000 in 2010); whereas the
      prevalence of diverticulitis was highest in whites (75.5/100,000 in 2010).
      CONCLUSIONS: Over the past 10 years, the prevalence of hospitalizations for
      diverticulitis increased and then plateaued, whereas that of diverticular
      bleeding decreased. The prevalence according to sex and race differed for
      diverticulitis and diverticular bleeding. These findings indicate different
      mechanisms of pathogenesis for these disorders.

PMID- 25862989
TI  - Proportion offered in the Dictator and Ultimatum Games decreases with amount and
      social distance.
AB  - Behavior in both the Dictator Game and the Ultimatum Game is of special interest
      because proposers often violate the predictions of normative economic theory: On
      average, offers in both games are higher than what would be considered income
      maximizing. In the present study, the initial amount provided to the proposer and
      the social distance between the proposer and the respondent were both varied
      across a wide range, and the effects of these manipulations on offers in the
      Dictator Game and the Ultimatum Game were examined in a broad sample of
      participants recruited via MTurk. Although the amount offered was consistently
      higher in the Ultimatum Game, the proportion of the amount offered decreased as
      the size of the initial amount increased in both games. Moreover, the proportion
      offered also decreased as a function of the social distance between the proposer
      and the responder. The present results extend our knowledge of the determinants
      of proposers' behavior in two-person economic games and emphasize the importance
      of social distance and the amount of money at stake as factors that affect
      people's economic decisions. 

PMID- 25862990
TI  - Characterization of cell-free extracts from fenpropathrin-degrading strain
      Bacillus cereus ZH-3 and its potential for bioremediation of pyrethroid
      contaminated soils.
AB  - Synthetic pyrethroid fenpropathrin has received increasing attention because of
      its environmental contamination and toxic effects on non-target organisms
      including human beings. Here we report the degradation characteristics of cell
      free extracts from fenpropathrin-degrading strain Bacillus cereus ZH-3 and its
      potential for pyrethroid bioremediation in soils. 50mg.L(-1) of fenpropathrin was
      decreased to 20.6mg.L(-1) by the enzymatic extracts (869.4mg.L(-1)) within 30min.
      Kinetic constants Km and Vm were determined to be 1006.7nmol.L(-1) and
      56.8nmol.min(-1), respectively. Degradation products were identified as 3
      phenoxybenzaldehyde, alpha-hydroxy-3-phenoxy-benzeneacetonitrile and phenol by
      gas chromatography-mass spectrometry (GC-MS). In addition to degradation of
      fenpropathrin, the cell-free extracts could degrade other pyrethroids including
      beta-cypermethrin, cyfluthrin, deltamethrin and cypermethrin. Additionally, the
      reaction conditions were optimized. In the sterile and non-sterile soils,
      50mg.kg(-1) of fenpropathrin was reduced to 15.3 and 13.9mg.L(-1) in 1d,
      respectively. Sprayed 100 and 300mg.kg(-1) of fenpropathrin emulsifiable
      concentrate (EC), up to 84.6% and 92.1% of soil fenpropathrin were removed from
      soils within 7d, respectively. Taken together, our results depict the
      biodegradation characteristics of cell-free extracts from B. cereus ZH-3,
      highlight its promising potential in bioremediation of pyrethroid-contaminated
      soils and also provide new insights into the utilization of degrading microbes. 

PMID- 25862991
TI  - The association between greenness and traffic-related air pollution at schools.
AB  - Greenness has been reported to improve mental and physical health. Reduction in
      exposure to air pollution has been suggested to underlie the health benefits of
      greenness; however, the available evidence on the mitigating effect of greenness
      on air pollution remains limited and inconsistent. We investigated the
      association between greenness within and surrounding school boundaries and
      monitored indoor and outdoor levels of traffic-related air pollutants (TRAPs)
      including NO2, ultrafine particles, black carbon, and traffic-related PM2.5 at 39
      schools across Barcelona, Spain, in 2012. TRAP levels at schools were measured
      twice during two one-week campaigns separated by 6months. Greenness within and
      surrounding school boundaries was measured as the average of satellite-derived
      normalized difference vegetation index (NDVI) within boundaries of school and a
      50m buffer around the school, respectively. Mixed effects models were used to
      quantify the associations between school greenness and TRAP levels, adjusted for
      relevant covariates. Higher greenness within and surrounding school boundaries
      was consistently associated with lower indoor and outdoor TRAP levels. Reduction
      in indoor TRAP levels was partly mediated by the reduction in outdoor TRAP
      levels. We also observed some suggestions for stronger associations between
      school surrounding greenness and outdoor TRAP levels for schools with higher
      number of trees around them. Our observed reduction of TRAP levels at schools
      associated with school greenness can be of public importance, considering the
      burden of health effects of exposure to TRAPs in schoolchildren. 

PMID- 25862992
TI  - Analyzing the contribution of climate change to long-term variations in sediment
      nitrogen sources for reservoirs/lakes.
AB  - We applied a mixing model based on stable isotopic delta(13)C, delta(15)N, and
      C:N ratios to estimate the contributions of multiple sources to sediment
      nitrogen. We also developed a conceptual model describing and analyzing the
      impacts of climate change on nitrogen enrichment. These two models were conducted
      in Miyun Reservoir to analyze the contribution of climate change to the
      variations in sediment nitrogen sources based on two (210)Pb and (137)Cs dated
      sediment cores. The results showed that during the past 50years, average
      contributions of soil and fertilizer, submerged macrophytes, N2-fixing
      phytoplankton, and non-N2-fixing phytoplankton were 40.7%, 40.3%, 11.8%, and
      7.2%, respectively. In addition, total nitrogen (TN) contents in sediment showed
      significant increasing trends from 1960 to 2010, and sediment nitrogen of both
      submerged macrophytes and phytoplankton sources exhibited significant increasing
      trends during the past 50years. In contrast, soil and fertilizer sources showed a
      significant decreasing trend from 1990 to 2010. According to the changing trend
      of N2-fixing phytoplankton, changes of temperature and sunshine duration
      accounted for at least 43% of the trend in the sediment nitrogen enrichment over
      the past 50years. Regression analysis of the climatic factors on nitrogen sources
      showed that the contributions of precipitation, temperature, and sunshine
      duration to the variations in sediment nitrogen sources ranged from 18.5% to
      60.3%. The study demonstrates that the mixing model provides a robust method for
      calculating the contribution of multiple nitrogen sources in sediment, and this
      study also suggests that N2-fixing phytoplankton could be regarded as an
      important response factor for assessing the impacts of climate change on nitrogen
      enrichment. 

PMID- 25862993
TI  - Polyethylene film incorporation into the horticultural soil of small periurban
      production units in Argentina.
AB  - Horticulture makes intensive use of soil and extensive use of polyethylene (PE)
      sheeting and pesticides, producing an environment where the dynamics between soil
      and plastics can affect pesticide fate. We have determined that the presence of
      plastic residues in the horticultural soil of small production units equals 10%
      of the soil area, being meso and macro-sections the predominant fragment sizes.
      All soil samples were taken from different plots located in Cuartel V, Moreno
      district, in the suburbs of Buenos Aires city, Argentina. Laboratory experiments
      were conducted to see the relations among pesticide, soil and PE film. Endosulfan
      recovery from LDPE films (25MUm and 100MUm) was studied, observing evidence that
      indicated migration to the inside of the plastic matrix. To further analyze the
      dynamics of pesticide migration to soil and atmosphere, experiments using
      chlorpyrifos, procymidone and trifluralin were performed in soil-plastic
      atmosphere microenvironments, showing that up to 24h significant amounts of
      pesticides moved away from the PE film. To determine whether PE residues could
      act as potential pesticide collector in soil, column elution experiments were
      done using chlorpyrifos, procymidone and trifluralin. Results showed an important
      pesticide accumulation in the mulch film (584MUg-2284MUg pesticide/g plastic)
      compared to soil (13MUg-32MUg pesticide/g soil). Finally, chemical and
      photochemical degradation of deltamethrin adsorbed in PE film was studied,
      finding a protective effect on hydrolysis but no protective effect on
      photodegradation. We believe that a deeper understanding of the dynamics among
      soil, plastic and pesticides in horticultural productive systems may contribute
      to alert for the implications of PE use for plastic sheeting. 

PMID- 25862994
TI  - Antimicrobial resistance determinants of Escherichia coli isolates recovered from
      some rivers in Osun State, South-Western Nigeria: Implications for public health.
AB  - The inevitable development of resistance has sunk the great success achieved in
      the discovery of antimicrobial agents and dashed the hope of man in the recovery
      from infections and illnesses, as diseases and disease agents that were once
      thought to be controlled by antimicrobials are now re-emerging in new leagues
      resistance to therapy. A total of 300 PCR confirmed Escherichia coli isolates
      recovered from different river sources in Osun State, Nigeria were evaluated for
      their antibiogram profiling by the disc diffusion method and the resistant
      isolates were further profiled for their genotypic antimicrobial resistance
      determinants by polymerase chain reaction assays. Among the 20 antimicrobials
      selected from 10 families, resistance among sulfonamides, beta-lactams and
      tetracyclines were found to be most frequent than phenicols and aminoglycosides
      with a noticeable increase in the number of multi-drug resistance ranging from
      three to nine antimicrobials. A total of 19 resistance determinants were assessed
      with their prevalence and distributions obtained as follows; [sulfonamides sulI
      (8%), sulII (41%)], [beta-lactams; ampC 22%; blaTEM, (21%), and blaZ (18%),],
      [tetracyclines tetA (24%), tetB (23%), tetC (18%), tetD (78%), tetK (15%), and
      tetM, (10%)], [phenicols; catI (37%), catII (28%), and cmIA1 (19%)] and
      [aminoglycosides; aacC2 (8%), aphA1 (80%), aphA2 (80%), aadA (79%) and strA
      (38%)]. The Pearson chi-square exact test revealed many strong significant
      associations among ampC, blaTEM, blaZ and tetA genes with some determinants
      screened. The findings signify high increase in the prevalence of multidrug
      resistant E. coli isolates and resistance determinants indicating increased
      public health risks associated with the ingestion of waters from untreated
      sources. Hence, a necessity for safe water supply, provision of proper sanitation
      facilities and good surveillance programmes to monitor antimicrobial resistance
      patterns in water bodies. 

PMID- 25862995
TI  - Simultaneous determination of iron (II) and ascorbic acid in pharmaceuticas based
      on flow sandwich technique.
AB  - The simple and easy performed flow system based on sandwich technique has been
      developed for the simultaneous separate determination of iron (II) and ascorbic
      acid in pharmaceuticals. The implementation of sandwich technique assumed the
      injection of sample solution between two selective reagents and allowed the
      carrying out in reaction coil two chemical reactions simultaneously: iron (II)
      with 1,10-phenanthroline and ascorbic acid with sodium 2,6
      dichlorophenolindophenol. For achieving of excellent repeatability and
      considerable reagent saving the various parameters such as flow rate, sample and
      reagent volumes, reaction coil length were also optimized. The limits of
      detection (LODs) obtained by using the developed flow sandwich-type approach were
      0.2 mg L(-1) for iron (II) and 0.7 mg L(-1) for ascorbic acid. The suggested
      approach was validated according to the following parameters: linearity and
      sensitivity, precision, recoveries and accuracy. The sampling frequency was 41 h(
      1).

PMID- 25862996
TI  - Differences in associations between active transportation and built environmental
      exposures when expressed using different components of individual activity
      spaces.
AB  - This study assessed relationships between built environmental exposures measured
      within components of individual activity spaces (i.e., travel origins,
      destinations and paths in-between), and use of active transportation in a
      metropolitan setting. Individuals (n=37,165) were categorised as using active or
      sedentary transportation based on travel survey data. Generalised Estimating
      Equations analysis was used to test relationships with active transportation.
      Strength and significance of relationships between exposures and active
      transportation varied for different components of the activity space.
      Associations were strongest when including travel paths in expression of the
      built environment. Land use mix and greenness were negatively related to active
      transportation. 

PMID- 25862997
TI  - Numerical simulation of airflow and micro-particle deposition in human nasal
      airway pre- and post-virtual sphenoidotomy surgery.
AB  - In the present study, the effects of endoscopic sphenoidotomy surgery on the flow
      patterns and deposition of micro-particles in the human nasal airway and sphenoid
      sinus were investigated. A realistic model of a human nasal passage including
      nasal cavity and paranasal sinuses was constructed using a series of CT scan
      images of a healthy subject. Then, a virtual sphenoidotomy by endoscopic sinus
      surgery was performed in the left nasal passage and sphenoid sinus. Transient
      airflow patterns pre- and post-surgery during a full breathing cycle (inhalation
      and exhalation) were simulated numerically under cyclic flow condition. The
      Lagrangian approach was used for evaluating the transport and deposition of
      inhaled micro-particles. An unsteady particle tracking was performed for the
      inhalation phase of the breathing cycle for the case that particles were
      continuously entering into the nasal airway. The total deposition pattern and
      sphenoid deposition fraction of micro-particles were evaluated and compared for
      pre- and post-surgery cases. The presented results show that sphenoidotomy
      increased the airflow into the sphenoid sinus, which led to increased deposition
      of micro-particles in this region. Particles up to 25 MUm were able to penetrate
      into the sphenoid in the post-operation case, and the highest deposition in the
      sphenoid for the resting breathing rate occurred for 10 MUm particles at about
      1.5%.

PMID- 25862998
TI  - Evolutionary growth of certain metabolic pathways involved in the functioning of
      GAD and INS genes in Type 1 Diabetes Mellitus: Their architecture and stability.
AB  - BACKGROUND: Studying biochemical pathway evolution for diseases is a flourishing
      area of Systems Biology. Here, we study Type 1 Diabetes Mellitus (T1D), focusing
      on growth of glutamate, beta-alanine, taurine and hypotaurine, and butanoate
      metabolisms involved in onset of GAD and INS genes in Homo sapiens with
      comparative analysis in non-obese diabetic Mus musculus, biobreeding Diabetes
      prone Rattus norvegicus, Pan troglodytes, Oryctolagus cuniculus, Danio rerio and
      Drosophila melanogaster respectively. METHODS: We propose an algorithm for growth
      analysis for four metabolic pathways involved in T1D. It has three modules,
      pattern finding, interaction identification and growth detection. The first
      module identifies patterns using Community structures using Hamming distances and
      the Tanimoto coefficient. We have performed functional analysis by representing
      patterns using ODEs, and identified Stoichiometric, Gradient and Jacobian
      matrices. The second module identifies interactions among patterns using cut-sets
      and network-partitioning by 'Divide-and-conquer'. The third module identifies
      functions of patterns using interactions, thereby highlighting their nature of
      growth. RESULTS: We observed that metabolites that are genetically robust and
      resist alterations against stable state during evolution, account for emergence
      of a scale-free network. DISCUSSION: New modules get acquired to the fundamental
      cluster in a preferential manner, an instance of micro-evolution theory. For
      instance, (S)-3-hydroxy butanoyl-CoA, acetoacetyl-CoA, acetoacetate, acetyl-CoA,
      (S)-3-hydroxy-3-methyl glutaryl-CoA acts as a fundamental cluster in butanoate
      metabolism. Moreover, the interactions among metabolites are divergent in nature.

PMID- 25862999
TI  - Data-driven modeling of pharmacological systems using endpoint information
      fusion.
AB  - This study investigated the feasibility of deriving data-driven model of a class
      of pharmacological systems using the information fusion of endpoint responses.
      For a class of pharmacological systems subsuming conventional steady-state dose
      response models, compartmental pharmacokinetic-pharmacodynamic models and
      indirect response models, a relation between multiple endpoint responses was
      formalized and analyzed to elucidate if this class of systems is identifiable,
      i.e., if the data-driven model of this class of systems can be derived from the
      endpoint responses alone. It was shown that this class of systems is fully
      identifiable in case all the responses involve effect compartments. However, it
      was also observed that persistently exciting dose profiles may be required in
      accurately deriving reliable data-driven model with low variance. The findings
      from the identifiability analysis were demonstrated using benchmark
      pharmacological system examples. 

PMID- 25863000
TI  - Allele frequency calibration for SNP based genotyping of DNA pools: A regression
      based local-global error fusion method.
AB  - BACKGROUND: The costs associated with developing high density microarray
      technologies are prohibitive for genotyping animals when there is low economic
      value associated with a single animal (e.g. prawns). DNA pooling is an attempt to
      address this issue by combining multiple DNA samples prior to genotyping. Instead
      of genotyping the DNA samples of the individuals, a mixture of DNA samples (i.e.
      the pool) from the individuals is genotyped only once. This greatly reduces the
      cost of genotyping. Pooled samples are subject to greater genotyping inaccuracies
      than individual samples. Wrong genotyping will lead to wrong biological
      conclusions. It is thus required to calibrate the resulting genotypes (allele
      frequencies). METHODS: We present a regression based approach to translate raw
      array output to allele frequency. During training, few pools and the individuals
      that constitute the pools are genotyped. Given the genotypes of individuals that
      constitute the pool, we compute the true allele frequency. We then train a
      regression algorithm to produce a mapping between the raw array outputs to the
      true allele frequency. We test the algorithm using pool samples withheld from the
      training set. During prediction, we use this map to genotype pools with no prior
      knowledge of the individuals constituting the pools. RESULTS AND DISCUSSION:
      After data quality control we have available a dataset comprised of 912 pools. We
      estimate allele frequency using three approaches: the raw data, a commonly used
      piecewise linear transformation, and the proposed local-global learner fusion
      method. The resulting RMS errors for the three approaches are 0.135, 0.120, and
      0.080 respectively.

PMID- 25863001
TI  - The effect of medical marijuana laws on adolescent and adult use of marijuana,
      alcohol, and other substances.
AB  - We estimate the effect of medical marijuana laws (MMLs) in ten states between
      2004 and 2012 on adolescent and adult use of marijuana, alcohol, and other
      psychoactive substances. We find increases in the probability of current
      marijuana use, regular marijuana use and marijuana abuse/dependence among those
      aged 21 or above. We also find an increase in marijuana use initiation among
      those aged 12-20. For those aged 21 or above, MMLs further increase the frequency
      of binge drinking. MMLs have no discernible impact on drinking behavior for those
      aged 12-20, or the use of other psychoactive substances in either age group. 

PMID- 25863002
TI  - Brief report: Peer group influences and adolescent internalizing problems as
      mediated by effortful control.
AB  - Internalizing problems in adolescence encompass behaviors directed inward at the
      self (Colman, Wadsworth, Croudace, & Jones, 2007). Several predictors have been
      linked to internalizing problems including antisocial and prosocial peers
      (Cartwright, 2007; Chung, 2010). Effortful control, a component of self
      regulation, is one factor that could mediate the relationship between peer
      behaviors and individual outcomes. This study assessed the relationship between
      peer behaviors, effortful control, and adolescent internalizing problems.
      Participants were 151 middle school adolescents (M = 12.16 years old) who
      completed self-report questionnaires regarding behaviors of their peers,
      perceptions of effortful control, and experiences of internalizing problems.
      Structural equation modeling (SEM) yielded a significant negative relationship
      between antisocial peers and effortful control, and a significant positive
      relationship between prosocial peers and effortful control. In addition,
      effortful control significantly mediated the relationship between prosocial peers
      and internalizing problems, but not for antisocial peers. Implications for
      interventions related to adolescent health were discussed. 

PMID- 25863003
TI  - Positive affective states and alcohol consumption: The moderating role of trait
      positive urgency.
AB  - Trait positive urgency is characterised by risky and maladaptive actions in
      response to extreme positive affective states. Positive urgency has previously
      been shown to be a risk factor for alcohol consumption and alcohol-related
      problems; however, there has been limited experimental research examining how
      positive urgency may moderate relations between affective states and alcohol
      consumption. In the current study, a sample of 106 participants completed a trait
      measure of positive urgency and were then randomly assigned to one of three mood
      induction conditions: a high-activation positive, a low-activation positive or a
      neutral mood condition. Subsequently, participants took part in a bogus beer
      taste test, where their alcohol consumption was subsequently measured. The
      results revealed that positive urgency significantly predicted increased beer
      consumption, but only for those participants in the high-activation positive mood
      induction group. The findings from this study provide support for positive
      urgency as a risk factor for alcohol use and suggest that it may be of particular
      relevance in social situations where individuals experience highly activated
      positive affective states. 

PMID- 25863004
TI  - A systematic review of secondhand tobacco smoke exposure and smoking behaviors:
      Smoking status, susceptibility, initiation, dependence, and cessation.
AB  - OBJECTIVES: To examine the association between secondhand tobacco smoke exposure
      (SHSe) and smoking behaviors (smoking status, susceptibility, initiation,
      dependence, and cessation). METHODS: Terms and keywords relevant to smoking
      behaviors and secondhand tobacco smoke exposure were used in a search of the
      PubMed database. Searches were limited to English language peer-reviewed studies
      up till December 2013. Included papers: a) had clearly defined measures of SHSe
      and b) had clearly defined measures of outcome variables of interest. A total of
      119 studies were initially retrieved and reviewed. After further review of
      references from the retrieved studies, 35 studies were finally selected that met
      all eligibility criteria. RESULTS: The reviewed studies consisted of thirty-five
      (89.7%) studies with differing measures of SHSe (including questionnaire and
      biological measures) and varying definitions of main outcome variables of
      interest between studies. The majority of the studies (77%) were cross-sectional
      in nature. The majority of studies found that SHSe was associated with greater
      likelihood of being a smoker, increased susceptibility and initiation of smoking,
      greater nicotine dependence among nonsmokers, and poorer smoking cessation.
      CONCLUSIONS: The review found positive associations between SHSe and smoking
      status, susceptibility, initiation and nicotine dependence and a negative
      association with smoking cessation. In light of design limitations, future
      prospective and clinical studies are needed to better understand the mechanisms
      whereby SHSe influences smoking behaviors.

PMID- 25863005
TI  - Gender differences in planning ability and hepatitis C virus among people who
      inject drugs.
AB  - Hepatitis C virus (HCV) is primarily spread through risky injection practices,
      including sharing needles, cookers, cottons, rinse water, and the practice of
      backloading. An important aspect of harm reduction for people who inject drugs
      (PWID) is to identify factors that contribute to safer injection. Planning
      ability may influence risky injection practices and gender differences in factors
      that drive injection practices indicate a need to examine associations between
      planning and injection behaviors in men versus women. Data from the NEURO-HIV
      Epidemiologic Study was restricted to those who had ever injected in their
      lifetime (n=456). Impaired planning ability was assessed with the Tower of London
      and defined as a standardized total excess move score below the 10th percentile.
      We used logistic regression to estimate the gender-specific adjusted odds ratios
      (AOR) and 95% confidence intervals (CI) for associations between impaired
      planning, each injection practice, and biologically-confirmed HCV. Impaired
      planning ability was associated with sharing needles (AOR=2.93, 95% CI: 1.33,
      6.47), cookers (AOR=3.13, 95% CI: 1.22, 8.02), cottons (AOR=2.89, 95% CI: 1.23,
      6.78), rinse water (AOR=2.43, 95% CI: 1.15, 5.14), and backloading (AOR=2.68, 95%
      CI: 1.26, 5.70) and HCV (AOR=3.42, 95% CI: 1.03, 11.38) among men. Planning
      ability was not significantly associated with the injection behaviors or HCV
      among women, suggesting that other factors likely contribute to risky injection
      practices. Interventions to promote harm reduction among PWID should ascertain
      and strengthen planning ability. Women may have additional barriers to practicing
      safe injection beyond impaired planning abilities, which should also be
      addressed. 

PMID- 25863006
TI  - Regionalized concentrations and fingerprints of polycyclic aromatic hydrocarbons
      (PAHs) in German forest soils.
AB  - Samples of 474 forest stands in Germany were analysed for concentrations of
      polycyclic aromatic hydrocarbons (PAHs) in three sampling depths. Enhanced
      concentrations were mainly found at spots relatively close to densely
      industrialized and urbanized regions and at some topographically elevated areas.
      Average enrichment factors between mineral soil and humic layer depend on humus
      type i.e. decrease from mull via moder to mor. Based on their compound-patterns,
      the observed samples could be assigned to three main clusters. For some parts of
      our study area a uniform assignment of samples to clusters over larger regions
      could be identified. For instance, samples taken at vicinity to brown-coal strip
      mining districts are characterized by high relative abundances of low-molecular
      weight PAHs. These results suggest that PAHs are more likely originated from
      local and regional emitters rather than from long-range transport and that
      specific source-regions can be identified based on PAH fingerprints. 

PMID- 25863007
TI  - Social phobia and quality of life in morbidly obese patients before and after
      bariatric surgery.
AB  - BACKGROUND: Morbidly obesity is characterized by physical and psychological
      comorbidities which are associated with reduced quality of life. Bariatric
      surgery has been linked to a reduction of psychopathology other than to a
      reduction of weight and improvement in physical functioning. Aim of the present
      study was to compare psychological features of two groups of morbidly obese
      patients, before and after bariatric surgery, assessing social phobia and quality
      of life. METHODS: A total of 46 morbidly obese patients were enrolled in the
      study. Of them, 20 were waiting for bilio-pancreatic diversion (group A), while
      26 had already undergone surgical procedure (group B). Psychometric evaluation
      assessed social phobia, fear for the body-shape and quality of life, using
      appropriate psychometric tests. RESULTS: The percentage of patients showing
      social phobia was significantly higher compared to a sample of healthy controls
      (p=0.004), both in group A (p=0.003) and in group B (p=0.029). No differences in
      percentage of patients affected by social phobia were found between groups. A
      significantly higher percentage of patients affected by distress about the body
      (p<0.0001) was found in group A with respect to group B. A reduction of quality
      of life was found in both groups. CONCLUSIONS: The present study shows a high
      prevalence of social phobia in a population of morbidly obese patients, both
      before and after surgery. A general reduction of quality of life was also
      observed, with a partial improvement after surgery. Future studies are needed to
      clarify the relationship between social phobia and quality of life in surgically
      treated morbidly obese patients.

PMID- 25863008
TI  - The use of complementary and alternative medicine in adults with depressive
      disorders. A critical integrative review.
AB  - BACKGROUND: Depression has been identified as one of the most frequent
      indications for CAM use and is a strong predictor of CAM use. The present article
      provides a critical review of CAM use for depressive disorders including bipolar
      depression by addressing prevalence of CAM use and CAM users' characteristics,
      motivation, decision-making and communication with healthcare providers. METHODS:
      A comprehensive search of 2003-2014 international literature in the Medline,
      CINAHL, AMED, and SCOPUS databases was conducted. The search was confined to peer
      reviewed articles published in English with abstracts and reporting new empirical
      research findings regarding CAM use and depressive disorders. RESULTS: A
      considerable level of CAM use was observed among both general and clinical
      populations of people suffering from depressive disorders, many of whom use CAM
      concurrently with their conventional medicine. In particular, high rates of CAM
      use were found among those with bipolar disorder, an illness known to cause
      substantial impairments in health-related quality of life. Concomitant
      prescription medication use ranged from 0.52% to as high as 100%. LIMITATIONS:
      Study design such as the inclusion of bipolar and depression in the same
      diagnostic category hamper the differentiation and attribution of CAM usage for
      symptoms. CONCLUSION: Findings of our review show that enduring impairments in
      function and persistence of symptoms (as reflected by increased CAM use
      proportional to severity of illness and comorbidity) are the impetus for
      sufferers of depressive illness to seek out CAM. The psychosocial factors
      associated with CAM use in depressive illnesses and severe mental illness are yet
      to be established. Subsequent research amongst those with depressive disorders
      would be informative in clarifying the range of motivations associated with
      mental illness.

PMID- 25863009
TI  - A constitutive model for ballistic gelatin at surgical strain rates.
AB  - This paper describes a constitutive model for ballistic gelatin at the low strain
      rates experienced, for example, by soft tissues during surgery. While this
      material is most commonly associated with high speed projectile penetration and
      impact investigations, it has also been used extensively as a soft tissue
      simulant in validation studies for surgical technologies (e.g. surgical
      simulation and guidance systems), for which loading speeds and the corresponding
      mechanical response of the material are quite different. We conducted mechanical
      compression experiments on gelatin specimens at strain rates spanning two orders
      of magnitude (~0.001-0.1s(-1)) and observed a nonlinear load-displacement history
      and strong strain rate-dependence. A compact and efficient visco-hyperelastic
      constitutive model was then formulated and found to fit the experimental data
      well. An Ogden type strain energy density function was employed for the elastic
      component. A single Prony exponential term was found to be adequate to capture
      the observed rate-dependence of the response over multiple strain rates. The
      model lends itself to immediate use within many commercial finite element
      packages. 

PMID- 25863010
TI  - Association of LRP5, TCF7L2, and GCG variants and type 2 diabetes mellitus as
      well as fasting plasma glucose and lipid metabolism indexes.
AB  - Recent data puts WNT signaling pathway in a pivotal role in regulating pancreas
      development as well as islet function, insulin production and secretion. The key
      effectors in the WNT signaling pathway are low-density lipoprotein receptor
      related protein 5 (LRP5), transcription factor 7-like 2 (TCF7L2), and downstream
      regulated glucagon (GCG). Our previous studies suggest that the WNT signaling
      pathway plays a significant role in risk of type 2 diabetes mellitus (T2DM) in
      Chinese population. The main purpose of the present study was to investigate the
      associations of single nucleotide polymorphisms (SNPs) in LRP5, TCF7L2 and
      glucagon (GCG) and quantitative traits in a healthy population. We used tag SNP
      to screen candidate SNPs for LRP5 and GCG; for TCF7L2, used the confirmed SNP
      rs11196218. A total of 1842 patients with T2DM and 7777 healthy controls
      underwent genotyping for the SNPs. We found a significant association of
      rs3758644 in LRP5 and fasting plasma glucose (p=0.006), and rs11196218 in TCF7L2
      and triglycerides level (p=0.004). Among the SNPs in LRP5, TCF7L2, and GCG
      analyzed, only rs3758644 of LRP5 and rs11196218 of TCF7L2 were significantly
      associated with fasting plasma glucose and triglycerides index, respectively, in
      a healthy population. 

PMID- 25863011
TI  - Cerebellar damage impairs internal predictions for sensory and motor function.
AB  - The cerebellum is connected to cerebral areas that subserve a range of sensory
      and motor functions. In this review, we summarize new literature demonstrating
      deficits in visual perception, proprioception, motor control, and motor learning
      performance following cerebellar damage. In particular, we highlight novel
      results that together suggest a general role of the cerebellum in estimating and
      predicting movement dynamics of the body and environmental stimuli. These
      findings agree with the hypothesized role of the cerebellum in the generation and
      calibration of predictive models for a variety of functions. 

PMID- 25863013
TI  - Octreotide for malignant bowel obstruction: commentary on Currow et al.

PMID- 25863015
TI  - Microbial dehalogenation of organohalides in marine and estuarine environments.
AB  - Marine sediments are the ultimate sink and a major entry way into the food chain
      for many highly halogenated and strongly hydrophobic organic pollutants, such as
      polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs),
      polybrominated diphenylethers (PBDEs) and 1,1,1-trichloro-2,2-bis(p
      chlorophenyl)ethane (DDT). Microbial reductive dehalogenation in anaerobic
      sediments can transform these contaminants into less toxic and more easily
      biodegradable products. Although little is still known about the diversity of
      respiratory dehalogenating bacteria and their catabolic genes in marine habitats,
      the occurrence of dehalogenation under actual site conditions has been reported.
      This suggests that the activity of dehalogenating microbes may contribute, if
      properly stimulated, to the in situ bioremediation of marine and estuarine
      contaminated sediments. 

PMID- 25863014
TI  - Participatory evaluation of a community-academic partnership to inform capacity
      building and sustainability.
AB  - The Tampa Bay Community Cancer Network (TBCCN) was formed as a partnership
      comprised of committed community based organizations (grassroots, service, health
      care organizations) and a National Cancer Institute designated cancer center
      working together to reduce cancer health disparities. Adhering to principles of
      community-based participatory research, TBCCN's primary aims are to develop and
      sustain outreach, training, and research programs that aim to reach medically
      underserved, multicultural and multilingual populations within the Tampa Bay tri
      county area. Using a participatory evaluation approach, we recently evaluated the
      partnerships' priorities for cancer education and outreach; perspectives on the
      partnerships' adherence to CBPR principles; and suggestions for sustaining TBCCN
      and its efforts. The purpose of this paper is to describe implementation and
      outcomes of this participatory evaluation of a community/academic partnership,
      and to illustrate the application of evaluation findings for partnership capacity
      building and sustainability. Our evaluation provides evidence for partners'
      perceived benefits and realized expectations of the partnership and illustrates
      the value of ongoing and continued partnership assessment to directly inform
      program activities and build community capacity and sustainability. 

PMID- 25863016
TI  - Near real-time determination of metabolic parameters for unquenched 6
      mercaptopurine and xanthine oxidase samples using capillary electrophoresis.
AB  - The enzyme activity of xanthine oxidase (XO) is influenced by several
      environmental factors including solution conditions, storage conditions,
      inhibitors, other enzymes, and activators. For instance, the metabolic reaction
      involving XO and the pro-drug 6-mercaptopurine, a drug used in the treatment
      maintenance of acute lymphatic leukemia, Crohn's disease, and ulcerative colitis,
      is often modified through the use of inhibitors, which varies the kinetic
      parameters associated with this reaction. Methods that provide fast and accurate
      determination of these kinetic constants can help in understanding the mechanism
      of these reactions. Herein, sequential and time-delayed electrokinetic injections
      of unpurified and unquenched samples containing xanthine oxidase, 6
      mercaptopurine, and the inhibitor allopurinol are evaluated using capillary
      electrophoresis (CE). Using progress curve analysis, the Michaelis constant,
      apparent Michaelis constant, and inhibition constant are estimated to be 43.8 +/-
      2.0 MUM, 143.0 +/- 3.7 MUM and 13.2 +/- 1.4 MUM, respectively. In addition, a
      turnover number of 7.9 +/- 0.2 min(-1) is quantified. These values are consistent
      with some previously published values but were obtained without user intervention
      for reaction monitoring. This unique application of CE enzyme assays offers
      substantial advantages over traditional methods by determining kinetic parameters
      for enzymatic reactions with minimal (nL) sample volumes, short (<30 min)
      reaction analysis times, without any sample quenching or purification, and
      minimal user intervention.

PMID- 25863017
TI  - Simultaneous determination of endocannabinoids in murine plasma and brain
      substructures by surrogate-based LC-MS/MS: Application in tumor-bearing mice.
AB  - The endocannabinoids (eCBs), N-arachidonoylethanolamine (anandamide, AEA) and 2
      ararchidonylglycerol (2-AG) have been identified as main endogenous ligands for
      cannabinoid receptors. Developing a sensitive and robust method to determine AEA
      and 2-AG has been shown to be essential to understand their effects in stress
      regulation and the pathogenesis of affective disorders. Since eCBs are endogenous
      molecules, there is no true blank matrix available to construct calibration
      curves, thus, it has been a challenge to determine eCBs in plasma and brain
      matrix. A liquid chromatography tandem mass spectrometry (LC-MS/MS) method is
      developed to determine the concentrations of AEA and 2-AG in murine plasma and
      different brain substructures (prefrontal cortex, hippocampus and hypothalamus).
      To overcome the endogenous interference, a "surrogate analyte" approach was
      adopted using stable isotope-labeled standards as surrogates of authentic
      analytes to generate calibration curves in biological matrix. The mobile phase,
      composed of formic acid 0.1% in water-acetonitrile (40:60, v/v), was optimized to
      separate 2-AG and its non-bioactive isomer 1-AG. The analytes were extracted with
      ethyl acetate/n-hexane (9:1, v/v) and separated on an Xbridge C18 (2.1 * 100 mm,
      3.5 MUm) column using N-Oleoylethanolamine-d2 (OEA-d2) as the internal standard.
      Detection was performed in multiple reaction monitoring (MRM) mode with an
      electrospray ionization source operated in positive ion mode. The method was
      applied to assess plasma and brain eCBs in tumor-bearing mice.

PMID- 25863018
TI  - A fast capillary electrophoresis method to assess the binding affinity of
      recombinant antithrombin toward heparin directly from cell culture supernatants.
AB  - With the aim to determine the binding affinity of a new generation of recombinant
      antithrombin (AT) toward heparin, we developed a dynamic equilibrium-affinity
      capillary electrophoresis (DE-ACE) method. This method allows the determination
      of an AT-heparin binding constant (Kd) directly from the cell culture supernatant
      used to produce the AT variants. Eight measurements per AT variant are sufficient
      to determine an accurate Kd (uncertainty <= 22%, regression coefficient >= 0.97),
      which is not significantly different from the value obtained from a higher number
      of measurements. Due to the relatively short time required to determine the Kd of
      one AT variant (2h), this method has the potential for being a low throughput
      screening method. The method was validated by analyzing five AT variants, whose
      Kd have been reported in the literature using fluorescence spectroscopy. Finally,
      the method was applied to estimate the Kd of one new AT variant and one AT
      conformer, a latent form, that exhibits a significant loss of affinity.

PMID- 25863019
TI  - Characterization of the impurities and isomers in cefetamet pivoxil hydrochloride
      by liquid chromatography/time-of-flight mass spectrometry and ion trap mass
      spectrometry.
AB  - Ten impurities and isomers in cefetamet pivoxil hydrochloride drug substance made
      in China were separated and identified by HPLC-MS(n) (TOF and TRAP). Their
      fragmentation patterns and structural assignment were studied based on the HPLC
      MS(n) data. Among the ten impurities and isomers, impurity VII was isolated by
      preparative HPLC, and its structure was confirmed by (1)H NMR data. 

PMID- 25863020
TI  - Secondary metabolites of Seseli rigidum: Chemical composition plus antioxidant,
      antimicrobial and cholinesterase inhibition activity.
AB  - Extracts of different polarity obtained from various plant parts (root, leaf,
      flower and fruit) of Seseli rigidum were studied by different antioxidant assays:
      DPPH and ABTS radical scavenging activity, by total reducing power method as well
      as via total content of flavonoids and polyphenols. Essential oils of all plant
      parts showed weak antioxidant characteristics. The inhibitory concentration range
      of the tested extracts, against bacteria Escherichia coli, Pseudomonas
      aeruginosa, Staphylococcus aureus, Bacillus cereus, and fungi Candida albicans
      and Aspergillus niger was 0.01-1.50 mg/mL and of a microbicidal 0.02-3.00 mg/mL.
      In the interaction with cholinesterase, all essential oils proved effective as
      inhibitors. The highest percentage of inhibition versus human and horse
      cholinesterase was shown by root essential oil (38.20% and 48.30%, respectively)
      among oils, and root hexane extract (40.56% and 50.65% respectively). Essential
      oils and volatile components of all plant parts were identified by GC, GC-MS and
      headspace/GC-MS. Statistical analysis of the ensemble of results showed that the
      root essential oil composition differed significantly from essential oils of
      other parts of the plant. Taking into account all of the studied activities, the
      root hexane extract showed the best overall properties. By means of high
      performance liquid chromatography coupled to high resolution mass spectrometry,
      the 30 most abundant constituents were identified in extracts of different
      polarity. The presence of identified constituents was linked to observed specific
      biological activities, thus designating compounds potentially responsible for
      each exhibited activity.

PMID- 25863021
TI  - Olfactory ensheathing cell-neurite alignment enhances neurite outgrowth in scar
      like cultures.
AB  - The regenerative capacity of adult CNS neurons after injury is strongly inhibited
      by the spinal cord lesion site environment that is composed primarily of the
      reactive astroglial scar and invading meningeal fibroblasts. Olfactory
      ensheathing cell (OEC) transplantation facilitates neuronal survival and
      functional recovery after a complete spinal cord transection, yet the mechanisms
      by which this recovery occurs remain unclear. We used a unique multicellular scar
      like culture model to test if OECs promote neurite outgrowth in growth-inhibitory
      areas. Astrocytes were mechanically injured and challenged by meningeal
      fibroblasts to produce key inhibitory elements of a spinal cord lesion. Neurite
      outgrowth of postnatal cerebral cortical neurons was assessed on three
      substrates: quiescent astrocyte control cultures, reactive astrocyte scar-like
      cultures, and scar-like cultures with OECs. Initial results showed that OECs
      enhanced total neurite outgrowth of cortical neurons in a scar-like environment
      by 60%. We then asked if the neurite growth-promoting properties of OECs depended
      on direct alignment between neuronal and OEC processes. Neurites that aligned
      with OECs were nearly three times longer when they grew on inhibitory meningeal
      fibroblast areas and twice as long on reactive astrocyte zones compared to
      neurites not associated with OECs. Our results show that OECs can independently
      enhance neurite elongation and that direct OEC-neurite cell contact can provide a
      permissive substrate that overcomes the inhibitory nature of the reactive
      astrocyte scar border and the fibroblast-rich spinal cord lesion core. 

PMID- 25863022
TI  - Seizure reduction through interneuron-mediated entrainment using low frequency
      optical stimulation.
AB  - Low frequency electrical stimulation (LFS) can reduce neural excitability and
      suppress seizures in animals and patients with epilepsy. However the therapeutic
      outcome could benefit from the determination of the cell types involved in
      seizure suppression. We used optogenetic techniques to investigate the role of
      interneurons in LFS (1Hz) in the epileptogenic hippocampus. Optical low frequency
      stimulation (oLFS) was first used to activate the cation channel channelrhodopsin
      2 (ChR2) in the Thy1-ChR2 transgenic mouse that expresses ChR2 in both excitatory
      and inhibitory neurons. We found that oLFS could effectively reduce epileptiform
      activity in the hippocampus through the activation of GAD-expressing hippocampal
      interneurons. This was confirmed using the VGAT-ChR2 transgenic mouse, allowing
      for selective optical activation of only GABA interneurons. Activating
      hippocampal interneurons through oLFS was found to cause entrainment of neural
      activity similar to electrical stimulation, but through a GABAA-mediated
      mechanism. These results confirm the robustness of the LFS paradigm and indicate
      that GABA interneurons play an unexpected role of shaping inter-ictal activity to
      decrease neural excitability in the hippocampus. 

PMID- 25863023
TI  - Novel hybrid DHPM-fatty acids: synthesis and activity against glioma cell growth
      in vitro.
AB  - We described the first synthesis of fatty acid 3,4-dihydropyrimidinones (DHPM
      fatty acids) using the Biginelli multicomponent reaction. Antiproliferative
      activity on two glioma cell lines (C6 rat and U-138-MG human) was also reported.
      The novel DHPM-fatty acids reduced glioma cell viability relative to
      temozolomide. Hybrid oxo-monastrol-palmitic acid was the most potent, reducing U
      138-MG human cell viability by ca. 50% at 10 MUM. In addition, the DHPM-fatty
      acids showed a large safety range to neural cells, represented by the organotypic
      hippocampal culture. These results suggest that the increased lipophilicity of
      DHPM-fatty acids offer a promising approach to overcoming resistance to
      chemotherapy and may play an important role in the development of new antitumor
      drugs. 

PMID- 25863024
TI  - Kinetics and energy efficiency for the degradation of 1,4-dioxane by electro
      peroxone process.
AB  - Degradation of 1,4-dioxane by ozonation, electrolysis, and their combined electro
      peroxone (E-peroxone) process was investigated. The E-peroxone process used a
      carbon-polytetrafluorethylene cathode to electrocatalytically convert O2 in the
      sparged ozone generator effluent (O2 and O3 gas mixture) to H2O2. The electro
      generated H2O2 then react with sparged O3 to yield aqueous OH, which can in turn
      oxidize pollutants rapidly in the bulk solution. Using p-chlorobenzoic acid as OH
      probe, the pseudo-steady concentration of OH was determined to be ~0.744*10(-9)mM
      in the E-peroxone process, which is approximately 10 and 186 times of that in
      ozonation and electrolysis using a Pt anode. Thanks to its higher OH
      concentration, the E-peroxone process eliminated 96.6% total organic carbon (TOC)
      from a 1,4-dioxane solution after 2h treatment with a specific energy consumption
      (SEC) of 0.376kWhg(-1) TOCremoved. In comparison, ozonation and electrolysis
      using a boron-doped diamond anode removed only ~6.1% and 26.9% TOC with SEC of
      2.43 and 0.558kWhg(-1) TOCremoved, respectively. The results indicate that the E
      peroxone process can significantly improve the kinetics and energy efficiency for
      1,4-dioxane mineralization as compared to the two individual processes. The E
      peroxone process may thus offer a highly effective and energy-efficient
      alternative to treat 1,4-dioxane wastewater. 

PMID- 25863026
TI  - Bioremediation of soils co-contaminated with heavy metals and 2,4,5
      trichlorophenol by fruiting body of Clitocybe maxima.
AB  - Pot experiments were performed to investigate the single effect of 2,4,5
      trichlorophenol (TCP) or heavy metals (Cu, Cd, Cu+Cd) and the combined effects of
      metals-TCP on the growth of Clitocybe maxima together with the accumulation of
      heavy metals as well as dissipation of TCP. Results showed a negative effect of
      contaminations on fruiting time and biomass of the mushroom. TCP decreased
      significantly in soils accounting for 70.66-96.24% of the initial extractable
      concentration in planted soil and 66.47-91.42% in unplanted soil, which showed
      that the dissipation of TCP was enhanced with mushroom planting. Higher
      biological activities (bacterial counts, soil respiration and laccase activity)
      were detected in planted soils relative to unplanted controls, and the enhanced
      dissipation of TCP in planted soils might be derived from the increased
      biological activities. The metals accumulation in mushroom increased with the
      augment of metal load, and the proportion of acetic acid (HOAc) extractable metal
      in soils with C. maxima was larger than that in unplanted soils, which may be an
      explanation of metal uptake by C. maxima. These results suggested that the
      presence of C. maxima was effective in promoting the bioremediation of soil
      contaminated with heavy metals and TCP. 

PMID- 25863025
TI  - Toxicity assessment due to sub-chronic exposure to individual and mixtures of
      four toxic heavy metals.
AB  - Humans are exposed to a cocktail of heavy metal toxicants in the environment.
      Though heavy metals are deleterious, there is a paucity of information on
      toxicity of low dose mixtures. In this study, lead (Pb) (0.01mg/L), mercury (Hg)
      (0.001mg/L), cadmium (Cd) (0.005mg/L) and arsenic (As) (0.01mg/L) were
      administered individually and as mixtures to 10 groups of 40 three-week old mice
      (20 males and 20 females), for 120 days. The study established that low dose
      exposures induced toxicity to the brain, liver, and kidney of mice. Metal
      mixtures showed higher toxicities compared to individual metals, as exposure to
      low dose Pb+Hg+Cd reduced brain weight and induced structural lesions, such as
      neuronal degeneration in 30-days. Pb+Hg+Cd and Pb+Hg+As+Cd exposure induced
      hepatocellular injury to mice evidenced by decreased antioxidant activities with
      marginal increases in MDA. These were accentuated by increases in ALT, AST and
      ALP. Interactions in metal mixtures were basically synergistic in nature and
      exposure to Pb+Hg+As+Cd induced renal tubular necrosis in kidneys of mice. This
      study underlines the importance of elucidating the toxicity of low dose metal
      mixtures so as to protect public health. 

PMID- 25863027
TI  - Prokaryotic functional gene diversity in the sunlit ocean: Stumbling in the dark.
AB  - Prokaryotes are extremely abundant in the ocean where they drive biogeochemical
      cycles. The recent development and application of -omics techniques has provided
      an astonishing amount of information revealing the existence of a vast diversity
      of functional genes and a large heterogeneity within each gene. The big challenge
      for microbial ecologists is now to understand the ecological relevance of this
      variability for ecosystem functioning, a question that remains largely
      understudied. This brief review highlights some of the latest advances in the
      study of the diversity of biogeochemically relevant functional genes in the
      sunlit ocean. 

PMID- 25863028
TI  - Biokinetics of different-shaped copper oxide nanoparticles in the freshwater
      gastropod, Potamopyrgus antipodarum.
AB  - Sediment is recognized as a major environmental sink for contaminants, including
      engineered nanoparticles (NPs). Consequently, sediment-living organisms are
      likely to be exposed to NPs. There is evidence that both accumulation and
      toxicity of metal NPs to sediment-dwellers increase with decreasing particle
      size, although NP size does not always predict effects. In contrast, not much is
      known about the influence of particle shape on bioaccumulation and toxicity.
      Here, we examined the influence of copper oxide (CuO) NP shape (rods, spheres,
      and platelets) on their bioaccumulation kinetics and toxicity to the sediment
      dwelling gastropod, Potamopyrgus antipodarum. The influence of Cu added as CuCl2
      (i.e., aqueous Cu treatment) was also examined. Exposure to sediment mixed with
      aqueous Cu or with different-shaped CuO NPs at an average measured exposure
      concentration of 207MUg Cu per g dry weight sediment for 14 days did not
      significantly affect snail mortality. However, growth decreased for snails
      exposed to sediment amended with CuO NP spheres and platelets. P. antipodarum
      accumulated Cu from all Cu forms/shapes in significant amounts compared to
      control snails. In addition, once accumulated, Cu was efficiently retained (i.e.,
      elimination rate constants were generally not significantly different from zero).
      Consequently, snails are likely to concentrate Cu over time, from both aqueous
      and NP sources, resulting in a high potential for toxicity. 

PMID- 25863029
TI  - Urbanisation shapes behavioural responses to a pesticide.
AB  - The degree of urbanisation is rapidly increasing worldwide. Due to anthropogenic
      impact, urban populations are exposed to higher levels of contaminants and higher
      temperatures. Despite this, urbanisation is a largely overlooked spatial
      component in ecotoxicology. We tested in a common garden rearing experiment
      whether replicated urban and rural populations of the damselfly Coenagrion puella
      differ in their vulnerability to sublethal levels of a widespread pesticide,
      chlorpyrifos, in terms of ecologically relevant behaviours (exploration
      behaviour, activity, boldness and food intake), and to what extent these patterns
      are affected by temperature (20 and 24 degrees C). Except boldness, all
      behaviours were affected by previous pesticide exposure. While the pesticide did
      not affect exploration behaviour at 20 degrees C, it was associated with
      increased exploration at 24 degrees C, which may reflect an increased toxicity of
      chlorpyrifos at higher temperatures. Importantly, rural and urban larvae showed
      consistently different, sometimes even opposite behavioural responses to
      pesticide exposure. When exposed to the pesticide, rural larvae decreased
      activity and food intake at both temperatures; urban larvae instead increased
      activity at both temperatures and only reduced food intake at the high
      temperature. This suggests that urban larvae were less affected by the pesticide,
      which would be consistent with a scenario of local adaptation to higher
      contaminant levels. Our results highlight that urbanisation may be an important
      factor to arrive at a spatially explicit ecological risk assessment, and may be
      an ignored reason why studies on the same species may generate widely different
      vulnerabilities to pesticides. 

PMID- 25863030
TI  - The effect of endurance training and downhill running on the expression of IL
      1beta, IL-6, and TNF-alpha and HSP72 in rat skeletal muscle.
AB  - This study investigated changes in the myokines IL-1beta, IL-6, and TNF-alpha, as
      well as HSP72, after endurance training and after a session of downhill running.
      Twenty-eight rats were allocated to four different groups: 1. Eight weeks of
      endurance training at 65-70% VO2max (Trained); 2. Endurance training and a single
      session of downhill running on a 16 degrees  slope (Trained plus downhill); 3. A
      single session of downhill running (Sedentary plus downhill); and 4. Sedentary
      (Control, no exercise). Soleus and extensor digitorum longus (EDL) muscles were
      harvested 48h after training and/or a single session of downhill running and
      protein levels of IL-1beta, IL-6, TNF-alpha, and HSP72 were measured and compared
      to the levels in the control animals. Creatine kinase (CK) was measured in
      plasma. Endurance training augmented intramuscular levels of HSP72 and IL-6 in
      both soleus and EDL muscles (p<0.05). Endurance training elevated IL-1beta and
      decreased TNF-alpha significantly only in EDL (P<0.05). IL-6 increased in both
      sedentary and trained rats after downhill running (P<0.05), while HSP72 increased
      only in the previously sedentary rats. CK was lower in trained than sedentary
      rats after downhill running. In conclusion, endurance training for 8weeks
      elevated muscular HSP72 protein levels, which might have preconditioned the
      muscles for a single session of downhill running, as indicated by the CK and
      HSP72 responses. Interestingly, IL-6 was augmented by endurance training and
      further increased by downhill running. IL-1beta, along with IL-6, was increased
      by endurance training, and these myokines thus appear to be differently regulated
      than TNF-alpha. 

PMID- 25863031
TI  - Luminescence properties of Tb(3+)-doped borosilicate scintillating glass under UV
      excitation.
AB  - Transparent Li2O-BaO-La2O3-Al2O3-B2O3-SiO2 glasses doped with Tb(3+) ion were
      prepared by high temperature melting method. Luminescence properties of Tb(3+)
      doped borosilicate glasses have been investigated by transmission, excitation,
      emission and luminescence decay measurements. The transmission spectrum shows the
      glass has good transmittance in the visible region. Under the 236 nm UV
      excitation the intense green emission from (5)D4 level is observed in Tb(3+)
      doped borosilicate glass, comparable in intensity to the violet-blue emission
      starting from the (5)D3 level. The green emission intensity of Tb(3+) ion firstly
      increases and then decreases with the decreasing B2O3/SiO2 ratio in glass matrix.
      (5)D4->(7)FJ (J=6, 5, 4 and 3) transitions of Tb(3+) ion in borosilicate glass
      are greatly enhanced with increasing concentration of Tb(3+) through the cross
      relaxation [Tb(3+) ((5)D3)+Tb(3+) ((7)F6)->Tb(3+) ((5)D4)+Tb(3+) ((7)F0)] between
      two Tb(3+) ions. Luminescence decay time of 2.13 ms is obtained for the emission
      transitions starting from (5)D4 level in 2.5Li2O-20BaO-20La2O3-2.5Al2O3-20B2O3
      35SiO2-0.5Tb4O7 glass. The results show that Tb(3+)-doped borosilicate glasses
      would be potential candidates for scintillating material for static X-ray
      imaging.

PMID- 25863032
TI  - Microhydration effects on geometric properties and electronic absorption spectra
      of ortho-aminobenzoic acid.
AB  - TD-DFT and a combination of polarized continuum model (PCM) and microhydration
      methods helped to simulate the optical electronic absorption spectrum of ortho
      aminobenzoic acid (o-Abz). The microhydration method involved the use of
      different numbers, from 1 to 5, of first solvation layer water molecules. We
      examined how implicit and explicit water affected the energies of the HOMO-LUMO
      transition in the o-Abz/water systems. Adding until five water molecules, the
      theoretical spectrum becomes closer to the experimental data. Microhydration
      combined with the PCM method leads to agreement between the theoretical result
      for five water molecules and the experimentally measured absorption bands. 

PMID- 25863033
TI  - The human whole blood pyrogen test - lessons learned in twenty years.
AB  - The whole blood pyrogen test was first described in this journal exactly twenty
      years ago. It employs the cytokine response of blood monocytes for the detection
      of microbiological contaminants with the potential to finally replace the still
      broadly used rabbit pyrogen test. The article reviews its development process,
      the current status of the test as well as the challenges and missed
      opportunities. The article highlights the enormous efforts of many people to get
      the test to where it is today. But it also shows the incredible missed
      opportunities for implementation and thus sparing about 400,000 rabbits still
      used for this purpose per year worldwide; in the EU, since the official
      acceptance of the test, the number of animals used for pyrogen testing did not
      fall but increased by about 10,000 to 170,000. The test is the first solution
      enabling adequate pyrogen testing of cell therapies, including blood
      transfusions, and medical devices, but has not been implemented for either
      application by authorities. As the test can quantitatively assess human-relevant
      airborne pyrogens, the contribution of pyrogens to chronic obstructive lung
      diseases and childhood asthma can for the first time be defined and home and
      workplace safety improved in the future.

PMID- 25863034
TI  - Synthesis of evidence: Working together on systematic reviews of animal studies.

PMID- 25863035
TI  - The role of in silico tools in supporting the application of the substitution
      principle.

PMID- 25863036
TI  - Long-Lived alphaMUPA Mice Show Reduced Sexual Dimorphism in Lifespan, and in
      Energy and Circadian Homeostasis-Related Parameters.
AB  - Female alphaMUPA (alpha murine urokinase-like plasminogen activator) transgenic
      mice show increased lifespan, reduced body weight and food intake, and high
      amplitude circadian rhythms with an endogenous period length (tau) of 24h, versus
      their wild types (WT) showing a 23.7-h tau. Our goal was to characterize
      alphaMUPA and WT male mice, and their in-strain sexual dimorphism, and to further
      understand the mechanisms underlying alphaMUPA's longevity. Male alphaMUPA mice
      showed increased lifespan, reduced body weight and food intake, and aligned
      endogenous rhythm with a tau of 24.0h versus a tau <24h in WT. However, no
      differences were found when intake was corrected for metabolic mass in male
      alphaMUPA mice. alphaMUPA's sexual dimorphism was damped or lacking in all
      studied traits, while WTs were sexually dimorphic, concluding that alphaMUPA's
      transgene overrides sex-dependent mechanisms involved in lifespan and in energy
      and circadian homeostasis. As enhanced resonance between tau and external
      circadian cycle correlates with increased lifespan and reduced body weight in
      other species, including humans, alphaMUPA's 24-h tau could contribute to their
      longevity. Focusing future research on the mechanistic interconnections between
      energy homeostasis, circadian homeostasis, sexual dimorphism, and aging, using
      alphaMUPA mice, may reveal mechanisms promoting reduced body weight and increased
      lifespan. 

PMID- 25863037
TI  - Towards dissecting molecular routes of intercellular communication in the tumour
      microenvironment: phenotypic plasticity of stem cell-associated markers in co
      culture (carcinoma cell/fibroblast) systems.
AB  - Increasing evidence attributes tumour fates to a small population of cells
      (cancer stem cells) capable of surviving therapeutic interventions. Investigation
      of their characteristics, especially in cross-talk with other cell types of the
      tumour microenvironment, can pave the way to innovative therapeutic concepts. The
      central issue of this study was to evaluate the impact of stroma on tumour cells
      with stem cell-like features in a squamous cell carcinoma model (FaDu). Six
      different types of experimental conditions were tested using distinct
      compositions of the culture system, and both morphologic and molecular features
      of the tumour cells were analysed. In detail, FaDu cells alone were used as a
      control, compared to tumour cells from co-culture, with squamous cell cancer
      derived stromal fibroblasts or normal skin human fibroblasts, both in the direct
      and indirect (insert) systems, adding analysis of side population cells of FaDu
      culture. Measurements were taken on days 2, 7 and 9 of culture and immediately
      after preparation in the case of the side population. A panel of antibodies
      against keratins 8, 10, 19, stem cell markers CD29, CD44, CD133, as well as
      biotinylated adhesion/growth-regulatory galectin 1 served as a toolbox for
      phenotypic characterization. Co-culture with fibroblasts prepared from tumour
      stroma and with dermal fibroblasts affected marker presentation, maintaining an
      undifferentiated stage phenotypically related to stem cells. Side-population
      cells showed close relationship to cancer stem cells in these characteristics. In
      conclusion, normal and tumour stromal fibroblasts are capable of shifting the
      marker expression profile of FaDu cells to a stem cell-like phenotypic pattern in
      co-culture.

PMID- 25863038
TI  - SKOV-3 and Me45 cell response to cisplatin-based chemotherapy: an in vitro study.
AB  - We studied malignant melanoma cell line Me45 and human ovarian carcinoma cell
      line SKOV-3 (resistant to cisplatin, adriamycin and diphtheria toxin), assessing
      their expression level of p53, HSP70 and glutathione S-transferase GST-pi before
      and after chemotherapy with cisplatin. These proteins may be responsible for the
      occurrence of chemoresistance in cancer patients. To assess protein expression we
      used the immunocytochemical Avidin-Biotin-peroxidase Complex (ABC) method. Before
      application of chemotherapy, proteins p53, HSP70 and GST-pi were present in 100 %
      of the examined melanoma cells. After the treatment, the intensity of the
      immunocytochemical reaction for p53 increased, whereas the intensity of
      immunocytochemical staining for HSP70 and GST-pi decreased. In SKOV-3 cells, p53
      and HSP70 were present in 100 % of the examined cells both prior to chemotherapy
      and after it. However, the intensity of the immunocytochemical reaction for p53
      decreased, while that of HSP70 increased. As regards GST-pi, only 5 % of all
      examined SKOV-3 cells revealed its expression before chemotherapy. Incubation
      with cisplatin caused an elevation in the number of ovarian cancer cells
      expressing GST-pi up to 50 %. Moreover, the intensity of the immunocytochemical
      reaction for GST-pi significantly increased. 

PMID- 25863039
TI  - Egg yolk phospholipids enriched with 1-O-octadecyl-2-oleoyl-sn-glycero-3-phospho
      (N-palmitoyl) ethanolamine inhibit development of experimentally induced tumours.
AB  - Dietary phospholipids (PLs) and their derivatives have proved active in
      suppression of various health problems and conditions including cancer. In this
      work we compared the effect of dietary phospholipids from hen egg yolk enriched
      with N-acyl ether-phosphatidyl ethanolamine (NAEPE) termed bioactive
      phospholipids (BAP+ preparation) with PLs lacking NAEPE (BAP- preparation) on the
      growth of transformed cells in vitro and on the promotion and progression of
      experimental tumours in vivo. For the in vivo experiments we used the chicken
      model in which liver, lung, and kidney tumours arose via natural selection from
      single cells initiated by experimentally introduced somatic mutations caused by
      insertional mutagenesis. Mutagenized animals were fed BAP+ or BAP- diet in
      various regimens. We observed that BAP+ at low concentrations killed cells of
      various tumour cell lines in culture but did not compromise viability of non
      transformed cells. Oral administration of the BAP+ preparation efficiently
      reduced progression of all tumour types. However, it did not significantly reduce
      the number of already initiated tumours and their growth when BAP+ was
      discontinued. Our data suggest that NAEPE combined with hen egg PLs significantly
      interferes with tumour progression, possibly through the inhibition of tumour
      cell viability. 

PMID- 25863040
TI  - Mycophenolate mofetil and cyclophosphamide treatments suppress inflammation
      intensity in an experimental model of autoimmune uveitis.
AB  - In human, autoimmune uveitis is a leading cause of visual disability and ranks
      with diabetic retinopathy as a major source of blind registrations in developed
      countries. Since most cases of non-infectious uveitis are considered to be
      autoimmune or at least immune-mediated, the management of such patients has
      rested on appropriate immunosuppression. Some patients, however, despite maximal
      immunotherapy, fail to respond or are seriously intolerant of the drug therapies.
      Since its establishment 20 years ago, the model of experimental autoimmune
      uveoretinitis has served as a useful template for novel therapeutic approaches.
      The aim of our study was to compare the efficacy of mycophenolate mofetil and
      cyclophosphamide and golimumab treatment in the mouse model of experimental
      autoimmune uveitis. The intensity of intraocular inflammation was evaluated
      histologically in the treatment and control groups. Experimental autoimmune
      uveitis has been induced in mouse strain C57BL/6 by subcutaneous application of
      interphotoreceptor retinoid binding protein in complete Freund's adjuvant and
      pertussis toxin. The treatment was commenced on the day of uveitis induction.
      Cyclophosphamide was applied intraperitoneally in a single dose (100 mg/kg),
      mycophenolate mofetil intraperitoneally daily (30 mg/kg or 50 mg/kg), golimumab
      subcutaneously weekly (70 mg/kg). Sham intraperitoneal injection of a placebo
      (aqua pro injectione) and untreated mice with experimental autoimmune uveitis
      served as controls. The results show statistically significant suppression of
      experimental uveitis both with mycophenolate mofetil and with cyclophosphamide,
      and thus support its use in human medicine. 

PMID- 25863041
TI  - Lipoprotein lipase deficiency: clinical, biochemical and molecular
      characteristics in three patients with novel mutations in the LPL gene.
AB  - Lipoprotein lipase (LPL) deficiency, caused by mutations in the LPL gene, is a
      rare autosomal recessive disorder manifesting in early childhood with recurrent
      abdominal pain, hepatosplenomegaly, acute pancreatitis, lipaemia retinalis and
      eruptive xanthomas. Typical laboratory findings are lactescent serum, extreme
      hypertriglyceridaemia and hypercholesterolaemia. The diagnostics is based on
      postheparin serum LPL assay and DNA analyses of the LPL gene. We report clinical,
      biochemical and molecular data of three children with LPL deficiency. One child
      manifested since the first week of life with recurrent abdominal pain (Patient
      1), the second with abdominal distension and hepatosplenomegaly since the second
      month of life (Patient 3) and patient 2, asymptomatic younger brother of patient
      1, was diagnosed in the first week of life. Lipaemia retinalis and splenomegaly
      were present in two symptomatic children, hepatomegaly in patient 3 and acute
      pancreatitis in patient 1. All children had lactescent serum, profound
      hypertriglyceridaemia (124 +/- 25 mmol/l; controls < 2.2), hypercholesterolaemia
      (22.8 +/- 7.3 mmol/l, controls < 4.2) and their LPL immunoreactive mass in serum
      did not increase after heparin injection. Molecular analyses revealed that both
      siblings are homozygous for novel mutation c.476C > G in the LPL gene changing
      the conserved amino acid of the catalytic centre. The third patient is a compound
      heterozygote for mutations c.604G>A and c.698A>G in the LPL gene, both affecting
      highly conserved amino acids. We conclude that LPL deficiency must be considered
      in neonates and young infants with abdominal pain and hypertriglyceridaemia
      because early treatment might prevent development of life-threatening acute
      pancreatitis. 

PMID- 25863042
TI  - Does folic acid supplementation rescue defects in ECE-1-deficient mouse embryos?
AB  - Endothelin (ET) signalling is essential for normal embryonic development.
      Disruption of this pathway leads to defects in the development of subsets of
      cranial and cephalic neural crest derivatives. Endothelin-converting enzyme 1
      (ECE-1) is a ratelimiting step in the biosynthesis of ET-1. Recently, there has
      been considerable interest in the protective role of folic acid (FA) against
      congenital anomalies via increasing the expression of ET-1. We have tested
      whether FA supplementation can rescue craniofacial and cardiac defects observed
      in the ECE1-/- embryos. ECE1+/- mice were caged together to obtain litters
      containing embryos of all possible genotypes. The treatment group had the diet
      supplemented with 20 mg/kg of FA from the day of discovery of the vaginal plug.
      FA supplementation did not result in modified proportions of the genotypes,
      indicating no rescue of the embryonic mortality. There was also no effect on the
      litter size. Craniofacial and cardiac defects were likewise identical in the ECE1
      /- embryos of both groups. There was a mild but significant reduction in the
      embryo size in wild-type and heterozygous FA-supplemented embryos, and there were
      haemorrhages in the wild-type supplemented embryos at ED14.5. Expression of ET
      receptor A detected by immunohistochemistry was up-regulated in the ECE1-/-
      embryos, but FA supplementation had no effects on the distribution of staining
      intensity. We conclude that FA is not able to rescue the phenotype in this model,
      suggesting an alternative pathway for its action. These results also caution
      against indiscriminate use of dietary supplements in attempts to prevent
      congenital anomalies. 

PMID- 25863043
TI  - [18F]fluorodeoxyglucose positron emission tomography/computed tomography can
      reveal subclinical prostatitis in a patient with IgG4-related disease.

PMID- 25863044
TI  - Asymptomatic cardiac involvement in Thai systemic sclerosis: prevalence and
      clinical correlations with non-cardiac manifestations (preliminary report).
AB  - OBJECTIVE: To determine the prevalence of asymptomatic cardiac involvement and
      its correlation with non-cardiac manifestation in Thai SSc patients. METHODS: A
      cross-sectional study was carried out between January 2012 and June 2013 at
      Srinagarind Hospital, Khon Kaen University, Thailand, on adult SSc patients
      without signs or symptoms suggestive of cardiac involvement. We excluded those
      with overlap syndrome, having serum creatinine >123.8 umol/l, history of cardiac
      diseases, any atherosclerosis risk factors and receiving angiotensin-converting
      enzyme inhibitors. Non-invasive tests related to cardiac involvement were
      performed, including: echocardiography, ECG, chest X-ray, inflammatory
      biomarkers, cardiac enzymes and N-terminal prohormone of brain natriuretic
      peptide. RESULTS: A total of 103 SSc patients were enrolled, 61.2% of whom were
      in the subset. Of these, 63 patients had at least one test abnormality
      (prevalence 61.2%; 95% CI 51.6, 70.7). The two leading cardiac abnormalities were
      diastolic dysfunction (44.7%) and elevation of cardiac enzymes (36.9%). The only
      predictor for cardiac involvement per multivariate analysis was the dcSSc subtype
      with a higher modified Rodnan skin score, and shorter disease duration (odds
      ratio = 3.37; 95% CI 1.07, 10.65). Compared with the limited subtype, dcSSc was
      also significantly associated with elevated cardiac enzyme and prolonged distance
      between a Q wave and T wave in an ECG (QT interval). CONCLUSION: Asymptomatic
      cardiac involvement in Thai SSc was not uncommon, and the most common finding was
      diastolic dysfunction. Elevated cardiac enzymes were found in one-third of the
      patients, which correlated with the dcSSc subtype with a higher modified Rodnan
      skin score and shorter disease duration, suggestive of early myocardial
      microcirculation disruption. Long-term follow-up was performed to elucidate the
      clinical implication of these abnormalities.

PMID- 25863045
TI  - The reliability and validity of the English version of the Evaluation of Daily
      Activity Questionnaire for people with rheumatoid arthritis.
AB  - OBJECTIVES: The Evaluation of Daily Activity Questionnaire (EDAQ) includes 138
      items in 14 domains identified as important by people with RA. The aim of this
      study was to test the validity and reliability of the English EDAQ. METHODS: A
      total of 502 participants completed two questionnaires 3 weeks apart. The first
      consisted of the EDAQ, HAQ, RA Quality of Life (RAQoL) and the Medical Outcomes
      Scale (MOS) 36-item Short-Form Health Survey (SF-36v2), and the second consisted
      of the EDAQ only. The 14 EDAQ domains were tested for: unidimensionality-using
      confirmatory factor analysis; fit, response dependency, invariance across groups
      (differential item functioning)-using Rasch analysis; internal consistency
      [Person Separation Index (PSI)]; concurrent validity-by correlations with the
      HAQ, SF-36v2 and RAQoL; and test-retest reliability (Spearman's correlations).
      RESULTS: Confirmatory factor analysis of the 14 EDAQ domains indicated
      unidimensionality, after adjustment for local dependency in each domain. All
      domains achieved a root mean square error of approximation <0.10 and satisfied
      Rasch model expectations for local dependency. DIF by age, gender and employment
      status was largely absent. The PSI was consistent with individual use (PSI = 0.94
      for all 14 domains). For all domains, except Caring, concurrent validity was
      good: HAQ (rs = 0.72-0.91), RAQoL (rs = 0.67-0.82) and SF36v2 Physical Function
      scale (rs = -0.60 to -0.84) and test-retest reliability was good (rs = 0.70
      0.89). CONCLUSION: Analysis supported a 14-domain, two-component structure (Self
      care and Mobility) of the EDAQ, where each domain, and both components, satisfied
      Rasch model requirements, and have robust reliability and validity.

PMID- 25863046
TI  - Catching protein structural dynamics by two-dimensional infrared spectroscopy.

PMID- 25863047
TI  - Understanding environmental adaptation of the fungal circadian clock with
      mathematical modeling.

PMID- 25863048
TI  - Seeing the unseen: cell strain and mechanosensing.

PMID- 25863049
TI  - A solid view of membrane proteins in situ.

PMID- 25863051
TI  - Front-to-rear membrane tension gradient in rapidly moving cells.
AB  - Membrane tension is becoming recognized as an important mechanical regulator of
      motile cell behavior. Although membrane-tension measurements have been performed
      in various cell types, the tension distribution along the plasma membrane of
      motile cells has been largely unexplored. Here, we present an experimental study
      of the distribution of tension in the plasma membrane of rapidly moving fish
      epithelial keratocytes. We find that during steady movement the apparent membrane
      tension is ~30% higher at the leading edge than at the trailing edge. Similar
      tension differences between the front and the rear of the cell are found in
      keratocyte fragments that lack a cell body. This front-to-rear tension variation
      likely reflects a tension gradient developed in the plasma membrane along the
      direction of movement due to viscous friction between the membrane and the
      cytoskeleton-attached protein anchors embedded in the membrane matrix.
      Theoretical modeling allows us to estimate the area density of these membrane
      anchors. Overall, our results indicate that even though membrane tension
      equilibrates rapidly and mechanically couples local boundary dynamics over
      cellular scales, steady-state variations in tension can exist in the plasma
      membranes of moving cells. 

PMID- 25863050
TI  - Altered mechanical environment of bone cells in an animal model of short- and
      long-term osteoporosis.
AB  - Alterations in bone tissue composition during osteoporosis likely disrupt the
      mechanical environment of bone cells and may thereby initiate a mechanobiological
      response. It has proved challenging to characterize the mechanical environment of
      bone cells in vivo, and the mechanical environment of osteoporotic bone cells is
      not known. The objective of this research is to characterize the local mechanical
      environment of osteocytes and osteoblasts from healthy and osteoporotic bone in a
      rat model of osteoporosis. Using a custom-designed micromechanical loading
      device, we apply strains representative of a range of physical activity (up to
      3000 MUepsilon) to fluorescently stained femur samples from normal and
      ovariectomized rats. Confocal imaging was simultaneously performed, and digital
      image correlation techniques were applied to characterize cellular strains. In
      healthy bone tissue, osteocytes experience higher maximum strains (31,028 +/-
      4213 MUepsilon) than osteoblasts (24,921 +/- 3,832 MUepsilon), whereas a larger
      proportion of the osteoblast experiences strains >10,000 MUepsilon. Most
      interestingly, we show that osteoporotic bone cells experience similar or higher
      maximum strains than healthy bone cells after short durations of estrogen
      deficiency (5 weeks), and exceeded the osteogenic strain threshold (10,000
      MUepsilon) in a similar or significantly larger proportion of the cell
      (osteoblast, 12.68% vs. 13.68%; osteocyte, 15.74% vs. 5.37%). However, in long
      term estrogen deficiency (34 weeks), there was no significant difference between
      bone cells in healthy and osteoporotic bone. These results suggest that the
      mechanical environment of bone cells is altered during early-stage osteoporosis,
      and that mechanobiological responses act to restore the mechanical environment of
      the bone tissue after it has been perturbed by ovariectomy. 

PMID- 25863052
TI  - The effect of substrate stiffness, thickness, and cross-linking density on
      osteogenic cell behavior.
AB  - Osteogenic cells respond to mechanical changes in their environment by altering
      their spread area, morphology, and gene expression profile. In particular, the
      bulk modulus of the substrate, as well as its microstructure and thickness, can
      substantially alter the local stiffness experienced by the cell. Although bone
      tissue regeneration strategies involve culture of bone cells on various
      biomaterial scaffolds, which are often cross-linked to enhance their physical
      integrity, it is difficult to ascertain and compare the local stiffness
      experienced by cells cultured on different biomaterials. In this study, we seek
      to characterize the local stiffness at the cellular level for MC3T3-E1 cells
      plated on biomaterial substrates of varying modulus, thickness, and cross-linking
      concentration. Cells were cultured on flat and wedge-shaped gels made from
      polyacrylamide or cross-linked collagen. The cross-linking density of the
      collagen gels was varied to investigate the effect of fiber cross-linking in
      conjunction with substrate thickness. Cell spread area was used as a measure of
      osteogenic differentiation. Finite element simulations were used to examine the
      effects of fiber cross-linking and substrate thickness on the resistance of the
      gel to cellular forces, corresponding to the equivalent shear stiffness for the
      gel structure in the region directly surrounding the cell. The results of this
      study show that MC3T3 cells cultured on a soft fibrous substrate attain the same
      spread cell area as those cultured on a much higher modulus, but nonfibrous
      substrate. Finite element simulations predict that a dramatic increase in the
      equivalent shear stiffness of fibrous collagen gels occurs as cross-linking
      density is increased, with equivalent stiffness also increasing as gel thickness
      is decreased. These results provide an insight into the response of osteogenic
      cells to individual substrate parameters and have the potential to inform future
      bone tissue regeneration strategies that can optimize the equivalent stiffness
      experienced by a cell. 

PMID- 25863053
TI  - Experimental verification of the kinetic theory of FRET using optical
      microspectroscopy and obligate oligomers.
AB  - Forster resonance energy transfer (FRET) is a nonradiative process for the
      transfer of energy from an optically excited donor molecule (D) to an acceptor
      molecule (A) in the ground state. The underlying theory predicting the dependence
      of the FRET efficiency on the sixth power of the distance between D and A has
      stood the test of time. In contrast, a comprehensive kinetic-based theory
      developed recently for FRET efficiencies among multiple donors and acceptors in
      multimeric arrays has waited for further testing. That theory has been tested in
      the work described in this article using linked fluorescent proteins located in
      the cytoplasm and at the plasma membrane of living cells. The cytoplasmic
      constructs were fused combinations of Cerulean as donor (D), Venus as acceptor
      (A), and a photo-insensitive molecule (Amber) as a nonfluorescent (N) place
      holder: namely, NDAN, NDNA, and ADNN duplexes, and the fully fluorescent
      quadruplex ADAA. The membrane-bound constructs were fused combinations of GFP2 as
      donor (D) and eYFP as acceptor (A): namely, two fluorescent duplexes (i.e., DA
      and AD) and a fluorescent triplex (ADA). According to the theory, the FRET
      efficiency of a multiplex such as ADAA or ADA can be predicted from that of
      analogs containing a single acceptor (e.g., NDAN, NDNA, and ADNN, or DA and AD,
      respectively). Relatively small but statistically significant differences were
      observed between the measured and predicted FRET efficiencies of the two
      multiplexes. While elucidation of the cause of this mismatch could be a worthy
      endeavor, the discrepancy does not appear to question the theoretical
      underpinnings of a large family of FRET-based methods for determining the
      stoichiometry and quaternary structure of complexes of macromolecules in living
      cells.

PMID- 25863054
TI  - Maintenance of motility bias during cyanobacterial phototaxis.
AB  - Signal transduction in bacteria is complex, ranging across scales from molecular
      signal detectors and effectors to cellular and community responses to stimuli.
      The unicellular, photosynthetic cyanobacterium Synechocystis sp. PCC6803
      transduces a light stimulus into directional movement known as phototaxis. This
      response occurs via a biased random walk toward or away from a directional light
      source, which is sensed by intracellular photoreceptors and mediated by Type IV
      pili. It is unknown how quickly cells can respond to changes in the presence or
      directionality of light, or how photoreceptors affect single-cell motility
      behavior. In this study, we use time-lapse microscopy coupled with quantitative
      single-cell tracking to investigate the timescale of the cellular response to
      various light conditions and to characterize the contribution of the
      photoreceptor TaxD1 (PixJ1) to phototaxis. We first demonstrate that a community
      of cells exhibits both spatial and population heterogeneity in its phototactic
      response. We then show that individual cells respond within minutes to changes in
      light conditions, and that movement directionality is conferred only by the
      current light directionality, rather than by a long-term memory of previous
      conditions. Our measurements indicate that motility bias likely results from the
      polarization of pilus activity, yielding variable levels of movement in different
      directions. Experiments with a photoreceptor (taxD1) mutant suggest a
      supplementary role of TaxD1 in enhancing movement directionality, in addition to
      its previously identified role in promoting positive phototaxis. Motivated by the
      behavior of the taxD1 mutant, we demonstrate using a reaction-diffusion model
      that diffusion anisotropy is sufficient to produce the observed changes in the
      pattern of collective motility. Taken together, our results establish that single
      cell tracking can be used to determine the factors that affect motility bias,
      which can then be coupled with biophysical simulations to connect changes in
      motility behaviors at the cellular scale with group dynamics. 

PMID- 25863055
TI  - Eisosomes are dynamic plasma membrane domains showing pil1-lsp1 heteroligomer
      binding equilibrium.
AB  - Eisosomes are plasma membrane domains concentrating lipids, transporters, and
      signaling molecules. In the budding yeast Saccharomyces cerevisiae, these domains
      are structured by scaffolds composed mainly by two cytoplasmic proteins Pil1 and
      Lsp1. Eisosomes are immobile domains, have relatively uniform size, and encompass
      thousands of units of the core proteins Pil1 and Lsp1. In this work we used
      fluorescence fluctuation analytical methods to determine the dynamics of eisosome
      core proteins at different subcellular locations. Using a combination of scanning
      techniques with autocorrelation analysis, we show that Pil1 and Lsp1 cytoplasmic
      pools freely diffuse whereas an eisosome-associated fraction of these proteins
      exhibits slow dynamics that fit with a binding-unbinding equilibrium. Number and
      brightness analysis shows that the eisosome-associated fraction is oligomeric,
      while cytoplasmic pools have lower aggregation states. Fluorescence lifetime
      imaging results indicate that Pil1 and Lsp1 directly interact in the cytoplasm
      and within the eisosomes. These results support a model where Pil1-Lsp1
      heterodimers are the minimal eisosomes building blocks. Moreover, individual
      eisosome fluorescence fluctuation analysis shows that eisosomes in the same cell
      are not equal domains: while roughly half of them are mostly static, the other
      half is actively exchanging core protein subunits. 

PMID- 25863056
TI  - A dynamic model of chemoattractant-induced cell migration.
AB  - Cell migration refers to a directional cell movement in response to
      chemoattractant stimulation. In this work, we developed a cell-migration model by
      mimicking in vivo migration using optically manipulated chemoattractant-loaded
      microsources. The model facilitates a quantitative characterization of the
      relationship among the protrusion force, cell motility, and chemoattractant
      gradient for the first time (to our knowledge). We verified the correctness of
      the model using migrating leukemia cancer Jurkat cells. The results show that one
      can achieve the ideal migrating capacity by choosing the appropriate
      chemoattractant gradient and concentration at the leading edge of the cell. 

PMID- 25863057
TI  - Hemagglutinin clusters in the plasma membrane are not enriched with cholesterol
      and sphingolipids.
AB  - The clusters of the influenza envelope protein, hemagglutinin, within the plasma
      membrane are hypothesized to be enriched with cholesterol and sphingolipids.
      Here, we directly tested this hypothesis by using high-resolution secondary ion
      mass spectrometry to image the distributions of antibody-labeled hemagglutinin
      and isotope-labeled cholesterol and sphingolipids in the plasma membranes of
      fibroblast cells that stably express hemagglutinin. We found that the
      hemagglutinin clusters were neither enriched with cholesterol nor colocalized
      with sphingolipid domains. Thus, hemagglutinin clustering and localization in the
      plasma membrane is not controlled by cohesive interactions between hemagglutinin
      and liquid-ordered domains enriched with cholesterol and sphingolipids, or from
      specific binding interactions between hemagglutinin, cholesterol, and/or the
      majority of sphingolipid species in the plasma membrane. 

PMID- 25863058
TI  - Electroporation of DC-3F cells is a dual process.
AB  - Treatment of biological material by pulsed electric fields is a versatile
      technique in biotechnology and biomedicine used, for example, in delivering DNA
      into cells (transfection), ablation of tumors, and food processing. Field
      exposure is associated with a membrane permeability increase usually ascribed to
      electroporation, i.e., formation of aqueous membrane pores. Knowledge of the
      underlying processes at the membrane level is predominantly built on theoretical
      considerations and molecular dynamics (MD) simulations. However, experimental
      data needed to monitor these processes with sufficient temporal resolution are
      scarce. The whole-cell patch-clamp technique was employed to investigate the
      effect of millisecond pulsed electric fields on DC-3F cells. Cellular membrane
      permeabilization was monitored by a conductance increase. For the first time, to
      our knowledge, it could be established experimentally that electroporation
      consists of two clearly separate processes: a rapid membrane poration (transient
      electroporation) that occurs while the membrane is depolarized or hyperpolarized
      to voltages beyond so-called threshold potentials (here, +201 mV and -231 mV,
      respectively) and is reversible within ~100 ms after the pulse, and a long-term,
      or persistent, permeabilization covering the whole voltage range. The latter
      prevailed after the pulse for at least 40 min, the postpulse time span tested
      experimentally. With mildly depolarizing or hyperpolarizing pulses just above
      threshold potentials, the two processes could be separated, since persistent (but
      not transient) permeabilization required repetitive pulse exposure. Conductance
      increased stepwise and gradually with depolarizing and hyperpolarizing pulses,
      respectively. Persistent permeabilization could also be elicited by single
      depolarizing/hyperpolarizing pulses of very high field strength. Experimental
      measurements of propidium iodide uptake provided evidence of a real membrane
      phenomenon, rather than a mere patch-clamp artifact. In short, the response of DC
      3F cells to strong pulsed electric fields was separated into a transient
      electroporation and a persistent permeabilization. The latter dominates postpulse
      membrane properties but to date has not been addressed by electroporation theory
      or MD simulations. 

PMID- 25863059
TI  - End-product diacylglycerol enhances the activity of PI-PLC through changes in
      membrane domain structure.
AB  - Diacylglycerol (DAG)-induced activation of phosphatidylinositol-phospholipase C
      (PI-PLC) was studied with vesicles containing PI, either pure or in mixtures with
      dimyristoyl phosphatidylcholine, distearoyl phosphatidylcholine, sphingomyelin,
      or galactosylceramide, used as substrates. At 22 degrees C, DAG at 33 mol %
      increased PI-PLC activity in all of the mixtures, but not in pure PI bilayers.
      DAG also caused an overall decrease in diphenylhexatriene fluorescence
      polarization (decreased molecular order) in all samples, and increased overall
      enzyme binding. Confocal fluorescence microscopy of giant unilamellar vesicles of
      all of the compositions under study, with or without DAG, and quantitative
      evaluation of the phase behavior using Laurdan generalized polarization, and of
      enzyme binding to the various domains, indicated that DAG activates PI-PLC
      whenever it can generate fluid domains to which the enzyme can bind with high
      affinity. In the specific case of PI/dimyristoyl phosphatidylcholine bilayers at
      22 degrees C, DAG induced/increased enzyme binding and activation, but no
      microscopic domain separation was observed. The presence of DAG-generated
      nanodomains, or of DAG-induced lipid packing defects, is proposed instead for
      this system. In PI/galactosylceramide mixtures, DAG may exert its activation role
      through the generation of small vesicles, which PI-PLC is known to degrade at
      higher rates. In general, our results indicate that global measurements obtained
      using fluorescent probes in vesicle suspensions in a cuvette are not sufficient
      to elucidate DAG effects that take place at the domain level. The above data
      reinforce the idea that DAG functions as an important physical agent in
      regulating membrane and cell properties. 

PMID- 25863060
TI  - In situ structural studies of Anabaena sensory rhodopsin in the E. coli membrane.
AB  - Magic-angle spinning nuclear magnetic resonance is well suited for the study of
      membrane proteins in the nativelike lipid environment. However, the natural
      cellular membrane is invariably more complex than the proteoliposomes most often
      used for solid-state NMR (SSNMR) studies, and differences may affect the
      structure and dynamics of the proteins under examination. In this work we use
      SSNMR and other biochemical and biophysical methods to probe the structure of a
      seven-transmembrane helical photoreceptor, Anabaena sensory rhodopsin (ASR),
      prepared in the Escherichia coli inner membrane, and compare it to that in a
      bilayer formed by DMPC/DMPA lipids. We find that ASR is organized into trimers in
      both environments but forms two-dimensional crystal lattices of different
      symmetries. It favors hexagonal packing in liposomes, but may form a square
      lattice in the E. coli membrane. To examine possible changes in structure site
      specifically, we perform two- and three-dimensional SSNMR experiments and analyze
      the differences in chemical shifts and peak intensities. Overall, this analysis
      reveals that the structure of ASR is largely conserved in the inner membrane of
      E. coli, with many of the important structural features of rhodopsins previously
      observed in ASR in proteoliposomes being preserved. Small, site-specific
      perturbations in protein structure that occur as a result of the membrane changes
      indicate that the protein can subtly adapt to its environment without large
      structural rearrangement. 

PMID- 25863061
TI  - Atomic-level mechanisms for phospholamban regulation of the calcium pump.
AB  - We performed protein pKa calculations and molecular dynamics (MD) simulations of
      the calcium pump (sarcoplasmic reticulum Ca(2+)-ATPase (SERCA)) in complex with
      phospholamban (PLB). X-ray crystallography studies have suggested that PLB locks
      SERCA in a low-Ca(2+)-affinity E2 state that is incompatible with metal-ion
      binding, thereby blocking the conversion toward a high-Ca(2+)-affinity E1 state.
      Estimation of pKa values of the acidic residues in the transport sites indicates
      that at normal intracellular pH (7.1-7.2), PLB-bound SERCA populates an E1 state
      that is deprotonated at residues E309 and D800 yet protonated at residue E771. We
      performed three independent microsecond-long MD simulations to evaluate the
      structural dynamics of SERCA-PLB in a solution containing 100 mM K(+) and 3 mM
      Mg(2+). Principal component analysis showed that PLB-bound SERCA lies exclusively
      along the structural ensemble of the E1 state. We found that the transport sites
      of PLB-bound SERCA are completely exposed to the cytosol and that K(+) ions bind
      transiently (<=5 ns) and nonspecifically (nine different positions) to the two
      transport sites, with a total occupancy time of K(+) in the transport sites of
      80%. We propose that PLB binding to SERCA populates a novel (to our knowledge) E1
      intermediate, E1?H(+)771. This intermediate serves as a kinetic trap that
      controls headpiece dynamics and depresses the structural transitions necessary
      for Ca(2+)-dependent activation of SERCA. We conclude that PLB-mediated
      regulation of SERCA activity in the heart results from biochemical and structural
      transitions that occur primarily in the E1 state of the pump. 

PMID- 25863062
TI  - Catch bond interaction between cell-surface sulfatase Sulf1 and
      glycosaminoglycans.
AB  - In biological adhesion, the biophysical mechanism of specific biomolecular
      interaction can be divided in slip and catch bonds, respectively. Conceptually,
      slip bonds exhibit a reduced bond lifetime under increased external force and
      catch bonds, in contrast, exhibit an increased lifetime (for a certain force
      interval). Since 2003, a handful of biological systems have been identified to
      display catch bond properties. Upon investigating the specific interaction
      between the unique hydrophilic domain (HD) of the human cell-surface sulfatase
      Sulf1 against its physiological glycosaminoglycan (GAG) target heparan sulfate
      (HS) by single molecule force spectroscopy (SMFS), we found clear evidence of
      catch bond behavior in this system. The HD, ~320 amino acids long with dominant
      positive charge, and its interaction with sulfated GAG-polymers were
      quantitatively investigated using atomic force microscopy (AFM) based force clamp
      spectroscopy (FCS) and dynamic force spectroscopy (DFS). In FCS experiments, we
      found that the catch bond character of HD against GAGs could be attributed to the
      GAG 6-O-sulfation site whereas only slip bond interaction can be observed in a
      GAG system where this site is explicitly lacking. We interpreted the binding data
      within the theoretical framework of a two state two path model, where two slip
      bonds are coupled forming a double-well interaction potential with an energy
      difference of DeltaE ~ 9 kBT and a compliance length of Deltax ~ 3.2 nm.
      Additional DFS experiments support this assumption and allow identification of
      these two coupled slip-bond states that behave consistently within the Kramers
      Bell-Evans model of force-mediated dissociation. 

PMID- 25863063
TI  - Buckling behavior of individual and bundled microtubules.
AB  - As the major structural constituent of the cytoskeleton, microtubules (MTs) serve
      a variety of biological functions that range from facilitating organelle
      transport to maintaining the mechanical integrity of the cell. Neuronal MTs
      exhibit a distinct configuration, hexagonally packed bundles of MT filaments,
      interconnected by MT-associated protein (MAP) tau. Building on our previous work
      on mechanical response of axonal MT bundles under uniaxial tension, this study is
      focused on exploring the compression scenarios. Intracellular MTs carry a large
      fraction of the compressive loads sensed by the cell and therefore, like any
      other column-like structure, are prone to substantial bending and buckling.
      Various biological activities, e.g., actomyosin contractility and many
      pathological conditions are driven or followed by bending, looping, and buckling
      of MT filaments. The coarse-grained model previously developed in our lab has
      been used to study the mechanical behavior of individual and bundled in vivo MT
      filaments under uniaxial compression. Both configurations show tip-localized,
      decaying, and short-wavelength buckling. This behavior highlights the role of the
      surrounding cytoplasm and MAP tau on MT buckling behavior, which allows MT
      filaments to bear much larger compressive forces. It is observed that MAP tau
      interconnections improve this effect by a factor of two. The enhanced ability of
      MT bundles to damp buckling waves relative to individual MT filaments, may be
      interpreted as a self-defense mechanism because it helps axonal MTs to endure
      harsher environments while maintaining their function. The results indicate that
      MT filaments in a bundle do not buckle simultaneously implying that the applied
      stress is not equally shared among the MT filaments, that is a consequence of the
      nonuniform distribution of MAP tau proteins along the bundle length. Furthermore,
      from a pathological perspective, it is observed that axonal MT bundles are more
      vulnerable to failure in compression than tension. 

PMID- 25863064
TI  - Free-energy landscape and characteristic forces for the initiation of DNA
      unzipping.
AB  - DNA unzipping, the separation of its double helix into single strands, is crucial
      in modulating a host of genetic processes. Although the large-scale separation of
      double-stranded DNA has been studied with a variety of theoretical and
      experimental techniques, the minute details of the very first steps of unzipping
      are still unclear. Here, we use atomistic molecular-dynamics simulations, coarse
      grained simulations, and a statistical-mechanical model to study the initiation
      of DNA unzipping by an external force. Calculation of the potential of mean force
      profiles for the initial separation of the first few terminal basepairs in a DNA
      oligomer revealed that forces ranging between 130 and 230 pN are needed to
      disrupt the first basepair, and these values are an order of magnitude larger
      than those needed to disrupt basepairs in partially unzipped DNA. The force peak
      has an echo of ~50 pN at the distance that unzips the second basepair. We show
      that the high peak needed to initiate unzipping derives from a free-energy basin
      that is distinct from the basins of subsequent basepairs because of entropic
      contributions, and we highlight the microscopic origin of the peak. To our
      knowledge, our results suggest a new window of exploration for single-molecule
      experiments. 

PMID- 25863065
TI  - Characterization of folding cores in the cyclophilin A-cyclosporin A complex.
AB  - Determining the folding core of a protein yields information about its folding
      process and dynamics. The experimental procedures for identifying the amino acids
      that make up the folding core include hydrogen-deuterium exchange and Phi-value
      analysis and can be expensive and time consuming. Because of this, there is a
      desire to improve upon existing methods for determining protein folding cores
      theoretically. We have obtained HDX data for the complex of cyclophilin A with
      the immunosuppressant cyclosporin A. We compare these data, as well as literature
      values for uncomplexed cyclophilin A, to theoretical predictions using a
      combination of rigidity analysis and coarse-grained simulations of protein
      motion. We find that in this case, the most specific prediction of folding cores
      comes from a combined approach that models the rigidity of the protein using the
      first software suite and the dynamics of the protein using the froda tool. 

PMID- 25863066
TI  - Structural disorder of folded proteins: isotope-edited 2D IR spectroscopy and
      Markov state modeling.
AB  - The conformational heterogeneity of the N-terminal domain of the ribosomal
      protein L9 (NTL91-39) in its folded state is investigated using isotope-edited
      two-dimensional infrared spectroscopy. Backbone carbonyls are isotope-labeled
      ((13)C=(18)O) at five selected positions (V3, V9, V9G13, G16, and G24) to provide
      a set of localized spectroscopic probes of the structure and solvent exposure at
      these positions. Structural interpretation of the amide I line shapes is enabled
      by spectral simulations carried out on structures extracted from a recent Markov
      state model. The V3 label spectrum indicates that the beta-sheet contacts between
      strands I and II are well folded with minimal disorder. The V9 and V9G13 label
      spectra, which directly probe the hydrogen-bond contacts across the beta-turn,
      show significant disorder, indicating that molecular dynamics simulations tend to
      overstabilize ideally folded beta-turn structures in NTL91-39. In addition, G24
      label spectra provide evidence for a partially disordered alpha-helix backbone
      that participates in hydrogen bonding with the surrounding water. 

PMID- 25863067
TI  - 13C, 2h NMR studies of structural and dynamical modifications of glucose-exposed
      porcine aortic elastin.
AB  - Elastin, the principal component of the elastic fiber of the extracellular
      matrix, imparts to vertebrate tissues remarkable resilience and longevity. This
      work focuses on elucidating dynamical and structural modifications of porcine
      aortic elastin exposed to glucose by solid-state NMR spectroscopic and relaxation
      methodologies. Results from macroscopic stress-strain tests are also presented
      and indicate that glucose-treated elastin is mechanically stiffer than the same
      tissue without glucose treatment. These measurements show a large hysteresis in
      the stress-strain behavior of glucose-treated elastin-a well-known signature of
      viscoelasticity. Two-dimensional relaxation NMR methods were used to investigate
      the correlation time, distribution, and population of water in these samples.
      Differences are observed between the relative populations of water, whereas the
      measured correlation times of tumbling motion of water across the samples were
      similar. (13)C magic-angle-spinning NMR methods were applied to investigate
      structural and dynamical modifications after glucose treatment. Although some
      overall structure is preserved, the process of glucose exposure results in more
      heterogeneous structures and slower mobility. The correlation times of tumbling
      motion of the (13)C-(1)H internuclear vectors in the glucose-treated sample are
      larger than in untreated samples, pointing to their more rigid structure. The
      (13)C cross-polarization spectra reveal a notably increased alpha-helical
      character in the alanine motifs after glucose exposure. Results from molecular
      dynamics simulations are provided that add further insight into dynamical and
      structural changes of a short repeat, [VPGVG]5, an alanine pentamer, desmosine,
      and isodesmosine sites with and without glucose. The simulations point to changes
      in the entropic and energetic contributions in the retractive forces of VPGVG and
      AAAAA motifs. The most notable change is the increase of the energetic
      contribution in the retractive force due to peptide-glucose interactions of the
      VPGVG motif, which may play an important role in the observed stiffening in
      glucose-treated elastin. 

PMID- 25863068
TI  - Transport regulation of two-dimensional receptor-ligand association.
AB  - The impact of flow disturbances on platelet adhesion is complex and incompletely
      understood. At the molecular scale, platelet glycoprotein Ibalpha (GPIbalpha)
      must associate with the von Willebrand factor A1 domain (VWF-A1) with a rapid on
      rate under high hemodynamic forces, as occurs in arterial thrombosis, where
      various transport mechanisms are at work. Here, we theoretically modeled the
      coupled transport-reaction process of the two-dimensional (2D) receptor-ligand
      association kinetics in a biomembrane force probe to explicitly account for the
      effects of molecular length, confinement stiffness, medium viscosity, surface
      curvature, and separation distance. We experimentally verified the theoretical
      approach by visualizing association and dissociation of individual VWF-A1
      GPIbalpha bonds in a real-time thermal fluctuation assay. The apparent on-rate,
      reciprocal of the average time intervals between sequential bonds, decreased with
      the increasing gap distance between A1- and GPIbalpha-bearing surfaces with an 80
      nm threshold (beyond which bond formation became prohibitive) identified as the
      combined contour length of the receptor and ligand molecules. The biomembrane
      force probe spring constant and diffusivity of the protein-bearing beads also
      significantly influenced the apparent on-rate, in accordance with the proposed
      transport mechanisms. The global agreement between the experimental data and the
      model predictions supports the hypothesis that receptor-ligand association
      behaves distinctly in the transport- and reaction-limited scenarios. To our
      knowledge, our results represent the first detailed quantification of physical
      regulation of the 2D on-rate that allows platelets to sense and respond to local
      changes in their hemodynamic environment. In addition, they provide an approach
      for determining the intrinsic kinetic parameters that employs simultaneous
      experimental measurements and theoretical modeling of bond association in a
      single assay. The 2D intrinsic forward rate for VWF-A1-GPIbalpha association was
      determined from the measurements to be (3.5 +/- 0.67) * 10(-4)MUm(2) s(-1). 

PMID- 25863069
TI  - Allosteric inhibitors have distinct effects, but also common modes of action, in
      the HCV polymerase.
AB  - The RNA-dependent RNA polymerase from the Hepatitis C Virus (gene product NS5B)
      is a validated drug target because of its critical role in genome replication.
      There are at least four distinct allosteric sites on the polymerase to which
      several small molecule inhibitors bind. In addition, numerous crystal structures
      have been solved with different allosteric inhibitors bound to the polymerase.
      However, the molecular mechanisms by which these small molecules inhibit the
      enzyme have not been fully elucidated. There is evidence that allosteric
      inhibitors alter the intrinsic motions and distribution of conformations sampled
      by the enzyme. In this study we use molecular dynamics simulations to understand
      the structural and dynamic changes that result when inhibitors are bound at three
      different allosteric binding sites on the enzyme. We observe that ligand binding
      at each site alters the structure and dynamics of NS5B in a distinct manner.
      Nonetheless, our studies also highlight commonalities in the mechanisms of action
      of the different inhibitors. Each inhibitor alters the conformational states
      sampled by the enzyme, either by rigidifying the enzyme and preventing
      transitions between functional conformational states or by destabilizing the
      enzyme and preventing functionally relevant conformations from being adequately
      sampled. By illuminating the molecular mechanisms of allosteric inhibition, these
      studies delineate the intrinsic functional properties of the enzyme and pave the
      way for designing novel and more effective polymerase inhibitors. This
      information may also be important to understand how allosteric regulation occurs
      in related viral polymerases and other enzymes. 

PMID- 25863070
TI  - Allosteric effects of sodium ion binding on activation of the m3 muscarinic g
      protein-coupled receptor.
AB  - G-protein-coupled receptors (GPCRs) are important membrane proteins that mediate
      cellular signaling and represent primary targets for about one-third of currently
      marketed drugs. Recent x-ray crystallographic studies identified distinct
      conformations of GPCRs in the active and inactive states. An allosteric sodium
      ion was found bound to a highly conserved D2.50 residue in inactive GPCRs,
      whereas the D2.50 allosteric pocket became collapsed in active GPCR structures.
      However, the dynamic mechanisms underlying these observations remain elusive. In
      this study, we aimed to understand the mechanistic effects of sodium ion binding
      on dynamic activation of the M3 muscarinic GPCR through long-timescale
      accelerated molecular dynamics (aMD) simulations. Results showed that with the
      D2.50 residue deprotonated, the M3 receptor is bound by an allosteric sodium ion
      and confined mostly in the inactive state with remarkably reduced flexibility. In
      contrast, the D2.50-protonated receptor does not exhibit sodium ion binding to
      the D2.50 allosteric site and samples a significantly larger conformational
      space. The receptor activation is captured and characterized by large-scale
      structural rearrangements of the transmembrane helices via dynamic hydrogen bond
      and salt bridge interactions. The residue motions are highly correlated during
      receptor activation. Further network analysis revealed that the allosteric
      signaling between residue D2.50 and key residues in the intracellular,
      extracellular, and orthosteric pockets is significantly weakened upon sodium ion
      binding. 

PMID- 25863071
TI  - Calcium enhances binding of Abeta monomer to DMPC lipid bilayer.
AB  - Using isobaric-isothermal replica-exchange molecular dynamics and the all-atom
      explicit-solvent model, we studied the equilibrium binding of Abeta monomers to a
      zwitterionic dimyristoylphosphatidylcholine (DMPC) bilayer coincubated with
      calcium ions. Using our previous replica-exchange molecular dynamics calcium-free
      simulations as a control, we reached three conclusions. First, calcium ions
      change the tertiary structure of the bound Abeta monomer by destabilizing several
      long-range intrapeptide interactions, particularly the salt bridge Asp(23)
      Lys(28). Second, calcium strengthens Abeta peptide binding to the DMPC bilayer by
      enhancing electrostatic interactions between charged amino acids and lipid polar
      headgroups. As a result, Abeta monomer penetrates deeper into the bilayer, making
      disorder in proximal lipids and bilayer thinning more pronounced. Third, because
      calcium ions demonstrate strong affinity to negatively charged amino acids, a
      considerable influx of calcium into the area proximal to the bound Abeta monomer
      is observed. Consequently, the localizations of negatively charged amino acids
      and calcium ions in the Abeta binding footprint overlap. Based on our data, we
      propose a mechanism by which calcium ions strengthen Abeta-bilayer interactions.
      This mechanism involves two factors: 1) calcium ions make the DMPC bilayer
      partially cationic and thus attractive to the anionic Abeta peptide; and 2)
      destabilization of the Asp(23)-Lys(28) salt bridge makes Lys(28) available for
      interactions with the bilayer. Finally, we conclude that a single Abeta monomer
      does not promote permeation of calcium ions through the zwitterionic bilayer. 

PMID- 25863072
TI  - Use of mechanistic models to integrate and analyze multiple proteomic datasets.
AB  - Proteins in cell signaling networks tend to interact promiscuously through low
      affinity interactions. Consequently, evaluating the physiological importance of
      mapped interactions can be difficult. Attempts to do so have tended to focus on
      single, measurable physicochemical factors, such as affinity or abundance. For
      example, interaction importance has been assessed on the basis of the relative
      affinities of binding partners for a protein of interest, such as a receptor.
      However, multiple factors can be expected to simultaneously influence the
      recruitment of proteins to a receptor (and the potential of these proteins to
      contribute to receptor signaling), including affinity, abundance, and
      competition, which is a network property. Here, we demonstrate that measurements
      of protein copy numbers and binding affinities can be integrated within the
      framework of a mechanistic, computational model that accounts for mass action and
      competition. We use cell line-specific models to rank the relative importance of
      protein-protein interactions in the epidermal growth factor receptor (EGFR)
      signaling network for 11 different cell lines. Each model accounts for
      experimentally characterized interactions of six autophosphorylation sites in
      EGFR with proteins containing a Src homology 2 and/or phosphotyrosine-binding
      domain. We measure importance as the predicted maximal extent of recruitment of a
      protein to EGFR following ligand-stimulated activation of EGFR signaling. We find
      that interactions ranked highly by this metric include experimentally detected
      interactions. Proteins with high importance rank in multiple cell lines include
      proteins with recognized, well-characterized roles in EGFR signaling, such as
      GRB2 and SHC1, as well as a protein with a less well-defined role, YES1. Our
      results reveal potential cell line-specific differences in recruitment. 

PMID- 25863073
TI  - Mathematical modeling and validation of glucose compensation of the neurospora
      circadian clock.
AB  - Autonomous circadian oscillations arise from transcriptional-translational
      feedback loops of core clock components. The period of a circadian oscillator is
      relatively insensitive to changes in nutrients (e.g., glucose), which is referred
      to as "nutrient compensation". Recently, a transcription repressor, CSP-1, was
      identified as a component of the circadian system in Neurospora crassa. The
      transcription of csp-1 is under the circadian regulation. Intriguingly, CSP-1
      represses the circadian transcription factor, WC-1, forming a negative feedback
      loop that can influence the core oscillator. This feedback mechanism is suggested
      to maintain the circadian period in a wide range of glucose concentrations. In
      this report, we constructed a mathematical model of the Neurospora circadian
      clock incorporating the above WC-1/CSP-1 feedback loop, and investigated
      molecular mechanisms of glucose compensation. Our model shows that glucose
      compensation exists within a narrow range of parameter space where the activation
      rates of csp-1 and wc-1 are balanced with each other, and simulates loss of
      glucose compensation in csp-1 mutants. More importantly, we experimentally
      validated rhythmic oscillations of the wc-1 gene expression and loss of glucose
      compensation in the wc-1(ov) mutant as predicted in the model. Furthermore, our
      stochastic simulations demonstrate that the CSP-1-dependent negative feedback
      loop functions in glucose compensation, but does not enhance the overall
      robustness of oscillations against molecular noise. Our work highlights
      predictive modeling of circadian clock machinery and experimental validations
      employing Neurospora and brings a deeper understanding of molecular mechanisms of
      glucose compensation. 

PMID- 25863074
TI  - Reproducibility of research in biophysics.

PMID- 25863075
TI  - [Mutations of phenylalanine hydroxylase gene detected in 20 patients with
      phenylketonuria from Yunnan Province].
AB  - OBJECTIVE: To investigate the mutations of phenylalanine hydroxylase (PAH) gene
      in 20 phenylketonuria (PKU) patients from Yunnan. METHODS: The 13 exons and the
      splicing regions of 12 introns of the PAH gene were sequenced to detect mutations
      in 20 unrelated PKU patients. RESULTS: PAH gene sequencing has revealed 15 types
      of mutations, in which the most frequently mutation was p.R243Q (30.0%), followed
      by p.Y356X(10.0%), p.R111X (7.5%), IVS4+2T>A (7.5%) and p.V399V (7.5%). Exons 7,
      11, 3 and introns 4, 11 were most frequently involved. Six novel mutations,
      including c.59A>C, c.60G>C, c.690_691insG, c.1119_1120insT, c.441+2T>A,
      c.842+4A>T and c.1200+1T>G were detected. CONCLUSION: PAH gene mutations
      identified in Yunnan are more similar to those of northern China, with R243R
      being the most common, though there are still certain characteristics for the
      type and frequency of mutations.

PMID- 25863076
TI  - [Genetic analysis of 36 children affected with phenylalanine hydroxylase
      deficiency from Fujian].
AB  - OBJECTIVE: To study the characteristics of phenylalanine hydroxylase gene (PAH)
      mutations in patients with PAH deficiency in Fujian population. METHODS:
      Peripheral blood samples of 36 patients and their parents with classical type
      phenylketouria (PKU) were collected. Genomic DNA was extracted. Following PCR
      amplification, DNA sequencing was carried out to identify the origins of
      mutations. RESULTS: Twenty types mutations were identified in 63 of the 72
      alleles. The most common mutations were R241C, R408Q and Ex6-96A>G, which
      respectively accounted for 15.9%, 12.7% and 11.1% of all mutant alleles. The
      c.189_190dupTGAC mutation was first reported. R241C was associated with 28% of
      mild hyperphenylalaninemia and R408Q is associated with 25% of classical PKU.
      CONCLUSION: There is a specific spectrum of PAH gene mutation in Fujian region.
      R241C, R408Q and Ex6-96A>G are the most common mutations.

PMID- 25863078
TI  - [Application of whole-genome and high-resolution chromosome microarray analysis
      for the investigation of fetuses with ultrasound abnormalities].
AB  - OBJECTIVE: To assess the value of whole-genome high-resolution chromosome
      microarray analysis (CMA) for the investigation of fetuses with ultrasound
      abnormalities. METHODS: Whole genome high-resolution CytoScanHD array from
      Affymetrix was employed to investigate 651 fetuses with structural abnormalities
      detected by ultrasound, for whom standard G-banded chromosome analysis has
      revealed a normal karyotype. The fetuses were divided into a single malformation
      group (n=264) and a multiple malformations group (n=387). In total there were 130
      chorionic villus samples, 192 amniotic fluid samples and 329 cord blood samples.
      Extraction of fetal DNA and CMA experiment have followed the standard guidelines
      from the manufacturers. All copy number variations (CNVs) detected by CMA were
      confirmed by fluorescence in situ hybridization (FISH) or real-time polymerase
      chain reaction (RT-PCR). RESULTS: CMA analysis has detected genomic CNVs in 475
      (73%) cases. Clinically significant CNVs were found in 11.5% (75/651) of fetuses,
      including two uniparental disomies (UPD) and two cryptic mosaicisms. Variations
      of unknown significance (VOUS) was found in 2.0% (13/651) of tested fetuses.
      CONCLUSION: Above results have suggested that whole-genome and high-resolution
      CMA is valuable for the analysis of fetuses with structural abnormalities
      detected by ultrasound, which can increase the detection rate by approximately
      11%. CMA using single nucleotide polymorphism (SNP) array has the ability to
      detect UPD and low-level mosaicisms. Sufficient communication between technicians
      and genetic counselors, parental testing and comparison the results with in-house
      and relevant online databases can significantly reduce the rate of VOUS.

PMID- 25863077
TI  - [Mitochondrial tRNA(Thr)T15943C mutation may be a new position that affects the
      phenotypic expression of deafness associated 12s rRNA A1555G mutation].
AB  - OBJECTIVE: To identify secondary mutations associated with deafness in a Chinese
      family affected with deafness. METHODS: The family has been subjected to clinical
      and molecular analyses, in addition with measurement of reactive oxygen species
      and doubling time after establishment of immortalized lymphocyte cell lines.
      RESULTS: The results showed that the hearing loss level and audiometric
      configuration were discrepant among the family members with maternally
      transmitted hearing loss. The penetrance of hearing loss in this family was
      respectively 66.7% and 44.4% when aminoglycoside-induced hearing loss was
      included or excluded. Analysis of whole mitochondrial genome has found 33
      variants as previously reported polymorphisms, except for a 12s rRNA A1555G
      mutation and a tRNA(Thr)T15943C mutation. Haplotype evolutionary tree has
      verified that this family belonged to East-Asian haplogroup F. 15943 position was
      located on the T-stem of the tRNA(Thr), which has destroyed the extremely
      conserved T-A base pair when T changed to C at this position. However, functional
      experiments indicated that the population doubling time in special galactose and
      glucose were longer, whilst the level of reactive oxygen species has increased.
      Compared with the control cell line groups and a family only carrying the 12s
      rRNA A1555G mutation, all of the three groups belonged to the same haplogroup.
      CONCLUSION: Mitochondrial tRNA(Thr)T15943C mutation may act as a potential
      modifying factor and interact with 12s rRNA A1555G mutation, and thereby enhance
      the penetrance and expression of deafness.

PMID- 25863079
TI  - [A pedigree with facioscapulohumerai muscular dystrophy].

PMID- 25863080
TI  - [Establishment of induced pluripotent stem cell lines from human amniotic fluid
      cells with 1q21.1 microdeletion].
AB  - OBJECTIVE: To reprogram the 1q21.1 microdeletion pluripotent stem cells in order
      to establish an ideal model for further studying its pathogenesis. METHODS: Human
      amniotic fluid-derived cells induced pluripotent stem cells (hAF-iPSCs) were
      induced from amniotic fluid cells harboring the 1q21.1 microdeletion by
      retroviral vectors encoding Oct4, Sox2, c-Myc and Klf4. Characteristics of the
      1q21.1 microdeletion hAF-iPSCs were determined, which included in vitro
      pluripotency, karyotype, microarray analysis, the capacity of differentiation in
      vivo and in vitro, etc. RESULTS: hAF-iPSCs derived from amniotic fluid cells
      harboring the 1q21.1 microdeletion have maintained self renewal, with expression
      of pluripotency marker genes detectable at mRNA level. Stem cell surface antigens
      were tested by immunocytochemistry. The 1q21.1 microdeletion hAF-iPSCs showed a
      normal karyotype after long-term culturing in vitro, and harbored the same
      microdeletion as confirmed by microarray analysis. The cells have maintained
      their differentiation capacity both in vivo and in vitro. CONCLUSION: The hAF
      iPSCs harboring the 1q21.1 microdeletion have all the characteristics of normal
      pluripotent stem cells, and can be used for directed differentiation into
      specific cells, which may provide an ideal model for studying the pathogenesis of
      1q21.1 microdeletion in vitro.

PMID- 25863081
TI  - [SNP microarray analysis of retention abortion chorionic villus].
AB  - OBJECTIVE: To compare villus cell culture and karyotype analysis with single
      nucleotide polymorphism (SNP) microarray technology for the detection of
      chorionic villus chromosome in patients with retention of abortion. METHODS:
      Forty cases were analyzed with the two methods. RESULTS: Chorionic villus
      culturing was successful in 29 cases, among which 10 were found to have an
      abnormal karyotypes. For the SNP microarray analysis, all 40 cases were
      successful, among which 16 were shown to have an abnormal molecular karyotype.
      CONCLUSION: SNP microarray technology is highly accurate and specific, which is
      particularly suitable for the detection of chromosomal deletions or duplications,
      uniparental disomy, low-percentage mosaicism and other chromosomal abnormalities.
      It has provided an effective supplement to the conventional chorionic villus
      culture and karyotype analysis.

PMID- 25863082
TI  - [Detection of common deafness-related genes among non-syndromic deafness patients
      from Shanxi province].
AB  - OBJECTIVE: To explore the common causative genes and mutation sites for
      hereditary non-syndromic deafness in Shanxi. METHODS: Peripheral blood samples
      were collected from regional schools for children with deafness. The samples were
      analyzed by matrix-assisted laser desorption ionization of flight mass
      spectrometry, and the results were verified by DNA sequencing. RESULTS: For all
      samples, the 20 mutational sites of the 4 common causative genes were tested. As
      revealed, c.235delC of GJB2 gene has the highest mutational rate (13.67%). c.IVS7
      2A>G of SLC26A (PDS) gene has a mutation rate of 17.67%, and c.1555A>G of
      mitochondrial 12S rRNA has a mutation rate of 2.00%. No mutations have been found
      with GJB3 gene. Sequencing analysis has suggested that the above results have a
      consistency rate of 99%. CONCLUSION: Analysis of mutations of the 4 common
      deafness-related genes can facilitate early diagnosis and treatment for the
      disease. Matrix-assisted laser desorption ionization time of flight mass
      spectrometry is a reliable method for such a task.

PMID- 25863083
TI  - [Mutation analysis of GCDH gene in four patients with glutaric academia type I].
AB  - OBJECTIVE: To report on clinical features of four patients with glutaric academia
      type I (GA-1) and mutations identified in the glutaryl-CoA dehydrogenase (GCDH)
      gene. METHODS: All of the patients underwent magnetic resonance imaging (MRI)
      analysis. Blood acylcarnitine and urine organic acid were analyzed with tandem
      mass spectrometry and gas chromatographic mass spectrometry. Genomic DNA was
      extracted from peripheral blood samples. The 11 exons and flanking sequences of
      the GCDH gene were amplified with PCR and subjected to direct DNA sequencing.
      RESULTS: Mutations of the GCDH gene were identified in all of the patients. Three
      had homozygous mutations. A recurrent mutation, IVS10-2A>C, was found in the four
      unrelated families, while the mutation of c.245G>C (p.Arg82Pro) was novel.
      CONCLUSION: IVS10-2A>C is likely a founder mutation for Chinese population in
      Wenzhou.

PMID- 25863084
TI  - [Identification of proteins interacting with the circadian clock protein PER1 in
      tumors using bacterial two-hybrid system technique].
AB  - OBJECTIVE: To identify protein-protein interaction partners of PER1 (period
      circadian protein homolog 1), key component of the molecular oscillation system
      of the circadian rhythm in tumors using bacterial two-hybrid system technique.
      METHODS: Human cervical carcinoma cell Hela library was adopted. Recombinant bait
      plasmid pBT-PER1 and pTRG cDNA plasmid library were cotransformed into the two
      hybrid system reporter strain cultured in a special selective medium. Target
      clones were screened. After isolating the positive clones, the target clones were
      sequenced and analyzed. RESULTS: Fourteen protein coding genes were identified, 4
      of which were found to contain whole coding regions of genes, which included
      optic atrophy 3 protein (OPA3) associated with mitochondrial dynamics and homo
      sapiens cutA divalent cation tolerance homolog of E. coli (CUTA) associated with
      copper metabolism. There were also cellular events related proteins and proteins
      which are involved in biochemical reaction and signal transduction-related
      proteins. CONCLUSION: Identification of potential interacting proteins with PER1
      in tumors may provide us new insights into the functions of the circadian clock
      protein PER1 during tumorigenesis.

PMID- 25863085
TI  - [Identification of mitochondrial DNA ND1 T3866C mutation in three ethnic Han
      Chinese families affected with Leber's hereditary optic neuropathy].
AB  - OBJECTIVE: To report on the clinical, genetic and molecular characteristics of
      three ethnic Han Chinese families affected with Leber's hereditary optic
      neuropathy (LHON). METHODS: The three families were all diagnosed with LHON.
      Ophthalmologic examinations were conducted on the probands . The ND1, ND4 and ND6
      genes of the mitochondrial DNA (mtDNA) were amplified with PCR respectively for
      the screening of three primary mutations G3460A, G11778A and T14484C. The entire
      mtDNA of the probands were also amplified by PCR. RESULTS: Analysis of mtDNA in
      the three pedigrees has failed to find the presence of the three LHON associated
      mutations but presence of a homoplastic ND1 T3866C mutation in all probands and
      their matrilineal relatives . The probands had different levels of visual
      impairment. The penetrance in the three families has been calculated as 12.5%,
      11.1% and 33.3%, respectively. The T3866C mutation has resulted in replacement of
      isoleucine at position 187 with theronine. The isoleucine at position 187 is
      located at one of the transmembrane domains of ND1 polypeptide. CONCLUSION: Above
      results have suggested that the ND1 T3866C mutation might have been involved in
      the pathogenesis of LHON in the three Chinese families studied.

PMID- 25863086
TI  - [Eight affected subjects in a Chinese family with autosomal dominant nonsyndromic
      hearing loss].

PMID- 25863087
TI  - [Molecular and prenatal diagnosis of a family with Fanconi anemia by next
      generation sequencing].
AB  - OBJECTIVE: To provide prenatal diagnosis for a pregnant woman who had given birth
      to a child with Fanconi anemia with combined next-generation sequencing (NGS) and
      Sanger sequencing. METHODS: For the affected child, potential mutations of the
      FANCA gene were analyzed with NGS. Suspected mutation was verified with Sanger
      sequencing. For prenatal diagnosis, genomic DNA was extracted from cultured fetal
      amniotic fluid cells and subjected to analysis of the same mutations. RESULTS: A
      low-frequency frameshifting mutation c.989_995del7 (p.H330LfsX2, inherited from
      his father) and a truncating mutation c.3971C>T (p.P1324L, inherited from his
      mother) have been identified in the affected child and considered to be
      pathogenic. The two mutations were subsequently verified by Sanger sequencing.
      Upon prenatal diagnosis, the fetus was found to carry two mutations. CONCLUSION:
      The combined next-generation sequencing and Sanger sequencing can reduce the time
      for diagnosis and identify subtypes of Fanconi anemia and the mutational sites,
      which has enabled reliable prenatal diagnosis of this disease.

PMID- 25863088
TI  - [Analysis of CSF1R gene mutation in a Chinese family with hereditary diffuse
      leukoencephalopathy with neuroaxonal spheroids].
AB  - OBJECTIVE: To identify potential mutation of the colony stimulating factor 1
      receptor gene (CSF1R) in a large Chinese family affected with hereditary diffuse
      leukoencephalopathy with spheroids (HDLS) and analyze the genotype-phenotype
      correlation. METHODS: The proband was evaluated physically and radiologically to
      ascertain the HDLS phenotype. Genomic DNA was extracted from peripheral blood
      samples from family members. The coding region of the CSF1R gene was amplified
      with PCR and subjected to direct DNA sequencing. RESULTS: There were 9 affected
      members (5 alive) in this five-generation family (1 member had died during the
      follow-up). A missense mutation c.2563C>A (p.P855T) of the CSF1R gene has been
      identified in the proband. The same mutation was identified in 3 affected and 1
      unaffected members of the family. CONCLUSION: The family was consistent with
      autosomal dominant inheritance. CSF1R gene mutation is also a disease-causing
      mutation in Chinese patients.

PMID- 25863089
TI  - [Genetic diagnosis for a Chinese Han family with primary hypertrophic
      osteoarthropathy].
AB  - OBJECTIVE: To identify the genetic cause for a Chinese Han family affected with
      primary hypertrophic osteoarthropathy. METHODS: Whole blood and urine samples
      were collected from a patient and 7 unaffected relatives of the family. The
      coding sequences and intron/exon boundaries of HPGD and SLCO2A1 genes of the
      patient were amplified with polymerase chain reaction and sequenced. The
      genotypes of relatives were subsequently verified. Urinary prostaglandin level
      was measured with enzyme-linked immunosorbent assay (ELISA). RESULTS: A
      homozygous 2-bp deletion in HPGD gene (c.310_311delCT, or p.L104AfsX3) was
      detected in the patient, and 5 heterozygous carriers were identified in the
      relatives. The urinary prostaglandin E2 (PGE2) level was significantly elevated
      (P<0.01), while PGE-M was significantly reduced (P<0.01) in the patient.
      CONCLUSION: Primary hypertrophic osteoarthropathy in this family is caused by a
      homozygous mutation (c.310_311delCT) in the HPGD gene.

PMID- 25863090
TI  - [Analysis of MUT gene mutations in a patient with isolated methylmalonic
      acidemia].
AB  - OBJECTIVE: To analyze the clinical features and mutation of MUT gene in a Chinese
      patient with isolated methylmalonic acidemia. METHODS: The clinical
      characteristics and laboratory tests data were collected. Genomic DNA was
      extracted from peripheral blood leukocytes. The 13 exons and their flanking
      sequences of the MUT gene were amplified with polymerase chain reaction and
      subjected to direct DNA sequencing. RESULTS: The patient has featured failure to
      thrive, lethargy, seizure, hypotonia, severe ketoacidosis and hyperammonemia.
      Tandem mass results showed reduction of multiple acylcarnitine. Urine organic
      acid testing showed pronounced increase in methylmalonate excretion. Homocysteine
      was normal. The patient showed no response to vitamin B12 treatment. The above
      results suggested that the patient had isolated methylmalonic acidemia. DNA
      sequencing analysis confirmed that the patient has carried two MUT gene
      mutations, c.755dupA and a novel mutation c.944dupT. CONCLUSION: Inherited
      metabolic disease screening plays an important role in the diagnosis of clinical
      diseases. However, to confirm the results will need gene mutation analysis.

PMID- 25863091
TI  - [Genetic analysis of a pedigree with hereditary coagulation factor VII
      deficiency].
AB  - OBJECTIVE: To identify potential mutations in a family affected with inherited
      factor VII (FVII) deficiency. METHODS: Prothrombin time (PT), activated partial
      thromboplastin time (APTT), fibrinogen, FVII activity (FVII:C) and other
      coagulant parameters of the proband and 15 family members were measured.
      Potential mutations were screened in the pedigree by polymerase chain reaction
      and direct DNA sequencing. RESULTS: The PT of the proband and his younger brother
      was significantly prolonged to 39.0 s and 30.1 s, respectively. FVII:C of the
      proband and his younger brother was obviously reduced to 2% and 3%, respectively.
      FVII:C of his grandmother, maternal grandmother, aunt, father, mother, maternal
      uncle and maternal aunt was all below the normal range (80%-108%), which measured
      68%, 54%, 71%, 73%, 62%, 72% and 59%, respectively. The other coagulant
      parameters were in the normal range. Two heterozygous mutations, g.11349G>A and
      g.11482T>G, both reside in exon 8 of the F7 gene, have resulted in p.Arg304Gln
      and p.His348Gln substitutions, were identified in the proband. The same mutations
      were also found in the proband's younger brother. Four maternal members in this
      family (grandmother, mother, maternal uncle and maternal aunt of the proband)
      were heterozygous for the p.Arg304Gln mutation, while three paternal members
      (grandmother, aunt and father of the proband) were heterozygous for the
      p.His348Gln mutation. CONCLUSION: The proband had inherited two independent
      mutations of the F7 gene including g.11349G>A and g.11482T>G from his mother and
      father, respectively. The compound heterozygous mutation probably explains the
      low FVII concentrations in this pedigree.

PMID- 25863092
TI  - [Diagnosis and prenatal diagnosis to a family of hemoglobin variant with alpha
      thalassemia].
AB  - OBJECTIVE: Diagnosis and prenatal diagnosis to a family of hemoglobin variant
      with alpha-thalassemia. METHODS: Whole blood cell analysis, hemoglobin analysis
      by capillary zone electrophoresis (CZE), Gap-PCR, polymerase chain reaction
      reverse dot blot (PCR-RDB) assay and DNA sequencing. RESULTS: Hb Zurich
      Albisrieden with alpha degrees -thalassemia lead to severe anemia. The genotype
      of fetus is also Hb Zurich Albisrieden with alpha degrees -thalassemia.
      CONCLUSION: Abnormal hemoglobin with alpha-thalassemia may lead to severe anemia,
      Prenatal diagnosis of thalassemia has the vital significance for eugenic birth.

PMID- 25863093
TI  - [Detection of chromosomal aneuploidies in spontaneous abortion samples by
      fluorescence in situ hybridization].
AB  - OBJECTIVE: To analyze 81 spontaneous abortion samples with fluorescence in situ
      hybridization (FISH). METHODS: Chromosome 13, 21, 16, 22, 18, X and Y probes were
      used to detect the samples. RESULTS: FISH was successful in 80 cases (98.77%).
      Among these, 35 (43.75%) had an abnormal karyotype, which included 19 autosomal
      aneuploidies, 6 sex chromosome aneuploidies, 9 triploidies and 1 tetraploidy.
      CONCLUSION: FISH is a rapid and easy method for detecting chromosomal
      aneuploidies in spontaneous abortion samples, and has a higher detection rate in
      early spontaneous abortion samples.

PMID- 25863094
TI  - [Genetic analysis and counseling for two fetal cases with large de novo Yq
      deletions].
AB  - OBJECTIVE: To analyze the deletion region for two fetal cases with large Yq
      deletions in order to provide genetic counseling and prenatal diagnosis. METHODS:
      For both cases, amniotic fluid samples were cultured and analyzed with G banding
      and fluorescence in situ hybridization (FISH). Multiplex polymerase chain
      reaction was also carried out to amplify 15 sequence tagged sites (STS) of
      azoospermia factor (AZF) on the Y chromosome. RESULTS: For both samples, the
      karyotypes were determined as 46,X,del(Y)(pter->q11:). No heterochromatin was
      found in C band. The karyotypes of their fathers were 46,XY, and heterochromatin
      was found in C band. STS analyses suggested that only sY82, sY84 and sY86 in AZFa
      were amplifiable while the other 12 STS were negative in amniotic fluid for the
      first case, which indicated deletions of AZFb, AZFd and AZFc. No AZF deletion was
      found in its father. For the second case, all 15 STS were amplifiable in the
      amniotic fluid, suggesting no AZF deletion. No AZF deletion was found in its
      father too. CONCLUSION: Conventional karyotyping combined with FISH and molecular
      genetics techniques can enable characterization of AZF microdeletions and
      facilitate genetic counseling and prenatal diagnosis.

PMID- 25863095
TI  - [Systematic genetic analysis for a case with duplication 9p].
AB  - OBJECTIVE: To identify the genetic cause for a case with growth retardation and
      mental retardation. METHODS: After conventional peripheral blood karyotyping with
      G-banding, the abnormal chromosome was identified as suspicious 9p duplication by
      multiplex ligation dependent probe amplification (MLPA) . RESULTS: The proband's
      karyotype was suspicious 46,XY,der(9)t(9;14)(q13;q11.2), then the abnormal
      chromosome 9 was identified as 9p duplication with MLPA. The 9p duplication
      occurs because of a balanced chromosomal rearrangement between two chromosomes of
      9 and 14 in the proband's father. CONCLUSION: 9p11.2-p24.3 duplication is the
      cause of abnormal phenotypes in the child patient. Cytogenetic methods combined
      with MLPA can efficiently identify abnormal chromosomes and provide accurate
      results for clinical diagnosis and treatment.

PMID- 25863096
TI  - [Identification of a novel mutation of COL2A1 gene in a Chinese family affected
      with spondyloepiphyseal dysplasia congenita].
AB  - OBJECTIVE: To identify potential disease-causing mutation in the COL2A1 gene in a
      Chinese family affected with autosomal dominant spondyloepiphyseal dysplasia
      congenita (SEDC; OMIM 183900) and to analyze the phenotype-genotype correlation.
      METHODS: Complete physical, and radiographic examinations of 4 affected
      individuals from the family were conducted. Genomic DNA was isolated from
      peripheral blood leukocytes. Whole-exome sequencing was performed using a
      HiSeq2000 sequencer. All 54 exons and exon-intron boundaries of the COL2A1 gene
      were amplified by polymerase chain reaction (PCR) and bidirectionally sequenced.
      RESULTS: All of the 4 individuals were found to carry a novel missense mutation
      of c.2224G>A (p.Gly687Ser) in the COL2A1 gene, while the same mutation was not
      found in the normal members of the family and 50 healthy controls. Protein
      prediction of missense mutation by Polyphen-2 and SIFT software indicated severe
      damage to the function. CONCLUSION: The mutation c.2224G>A (p.Gly687Ser) of the
      COL2A1 gene is responsible for this family. There are heterozygous of phenotype
      for the mutation.

PMID- 25863097
TI  - [Association study between -765G > C and -1195G > A functional polymorphisms in
      the cyclooxygenase 2 gene and risk of preeclampsia].
AB  - OBJECTIVE: To investigate the relationship between two polymorphisms immediately
      upstream of the cyclooxygenase 2 (COX2) gene and preeclampsia in a South West Han
      Chinese population. METHODS: Blood samples from 205 patients with preeclampsia
      and 276 normal pregnant women as controls from Han Chinese in Chengdu area were
      analyzed by polymerase chain reaction-restriction fragment length polymorphisms.
      RESULTS: G and A allele frequencies for -1195G>A site were 48.54% and 51.46% in
      the patient group, respectively, and 40.40% and 59.60% in the control group,
      respectively. G and C allele frequencies for -765G>C site were 94.15% and 5.85%
      in the case group, respectively, and 94.38% and 5.62% in the control group,
      respectively. The AA genotype and variant A allelic frequencies of the -1195G>A
      SNP were significantly lower in patients with preeclampsia than in the control
      group (P<0.05), and the odds ratio for the risk of preeclampsia was 0.665 (95%
      CI: 0.444-0.982) in women homozygous for the variant COX2 A allele ( x2=4.233,
      P=0.047). The genotype and allele frequencies of the -765G>C polymorphism in
      patients with preeclampsia and controls showed no significant differences
      (P>0.05). Additional subgroup analyses (mild vs severe preeclampsia) of the two
      polymorphisms failed to reveal significant correlation for either genotypic or
      allelic frequencies. Furthermore, there was no significant association between
      the polymorphisms and blood pressure levels in the patient or control groups.
      CONCLUSION: COX2 -1195A homozygosity is associated with a decreased risk for
      preeclampsia in a South West Han Chinese population. On the other hand, the 
      765G>C polymorphism has no effect.

PMID- 25863098
TI  - [Molecular basis for an individual with rare p phenotype in P1Pk blood group
      system].
AB  - OBJECTIVE: To explore the molecular basis for an individual with rare p phenotype
      in the P1Pk blood group system. METHODS: Erythrocyte blood group antigens and
      antibodies in serum were identified in the proband and five family members with a
      serological method. Coding regions and flanking untranslated regions of the
      alpha1,4-galactosyltransferase gene (A4GALT) encoding P1Pk antigens were
      amplified with polymerase chain reaction and directly sequenced. The haplotypes
      of A4GALT in the parents of the proband were also analyzed by cloning sequencing.
      RESULTS: The proband was found with a rare p phenotype with anti-Tja antibody in
      his serum by serological method. The other family members all had a common P2
      phenotype. The results of DNA sequencing showed that a cytosine was inserted at
      nucleotide position 1026 to 1029 (1026_1029insC) of both alleles of the A4GALT
      gene in the proband. The mutation has caused a reading frame shift and formed a
      mutant protein by extending 92 amino acid residues. The other family members were
      either heterozygous for the insertion or of the wild type at above position.
      CONCLUSION: The 1026_1029insC mutation of the A4GALT gene is probably responsible
      for the p phenotype identified for the first time in Chinese population. The
      individual with the p phenotype possesses anti-Tja antibody.

PMID- 25863099
TI  - [Association of HLA-DPA1 and -DPB1 polymorphisms with Posner-Schlossman syndrome
      among southern Chinese Han population].
AB  - OBJECTIVE: To assess the association of HLA-DPA1 and -DPB1 polymorphisms with
      Posner-Schlossman syndrome (PSS) in southern Chinese Han population. METHODS: A
      total of 100 randomly selected PSS patients of southern Chinese Han origin were
      served as the experimental group, while 128 unrelated healthy blood donors of the
      same origin were served as the control group. All samples were subjected to
      sequencing-based typing (SBT) for exon 2 of HLA-DPA1 and -DPB1 loci in both
      directions. HLA genotype was assigned using an Assign 3.5 HLA SBT software. The
      allele frequencies and haplotype frequencies of HLA-DPA1 and -DPB1 of the two
      groups were compared. x2 test, P value and odds ratio (OR) value were calculated.
      RESULTS: Six HLA-DPA1 alleles in the experimental group and 4 HLA-DPA1 alleles in
      the healthy control group were identified. The allelic frequency for HLA
      DPA1*02:01 in the experimental group was significantly lower than the control
      group (4.50% vs. 12.109%; x2=8.124, P=0.004). Sixteen HLA-DPB1 alleles were
      identified in both the experimental and control groups. The allelic frequencies
      for HLA-DPB1*14:01 and - DPB1*17:01 in the experimental group were significantly
      lower than those of the control group ( DPB1*14:01: 1.00% vs. 4.688%, x2=5.130,
      P=0.024; DPB1*17:01: 0% vs. 2.344%, x2=3.897, P=0.048). The DPA1-DPB1 haplotypes
      for the experimental and control groups were 23 and 25, respectively. The
      haplotype frequencies for both DPA1*02:01- DPB1*14:01 and DPA1*02:01- DPB1*17:01
      were significantly lower than those of the control group. CONCLUSION: DPA1*02:01-
      DPB1*14:01 and DPA1*02:01- DPB1*17:01 haplotypes may provide considerable
      protection effect against PSS in the southern Chinese Han population.

PMID- 25863100
TI  - [Difference in brain surface area between first-episode familial and sporadic
      schizophrenia and its association with COMT gene polymorphisms].
AB  - OBJECTIVE: To assess the association of impairment of surface area of first
      episode schizophrenia(SZ) with polymorphisms of COMT gene, and the difference in
      the impaired patterns between familial patients with schizophrenia(FPS) and
      sporadic patients with schizophrenia(SPS). METHODS: Ninety-eight patients with
      first-episode SZ(FPS=40, SPS=58) and 78 healthy controls were recruited. COMT
      gene was genotyped by polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) method. Participants were scanned for 3.0T magnetic
      resonance images. Freesurfer software was used to analyze the difference in brain
      surface area between SZ and controls, its association with COMT genotypes, and
      the difference between SPS, FPS and control groups. Multiple tests were corrected
      using a Monte Carlo simulation at P<0.05. RESULTS: Compared with controls, SZ
      showed decreased surface area in right occipital cortex and left prefrontal
      cortex. No association was found between COMT polymorphisms and whole brain area
      difference. Among the three subgroups, SPS showed smaller left prefrontal area
      compared with both FPS and control groups. Patients with SPS also showed
      significant area reduction in right occipital lobe compared with controls.
      CONCLUSION: Surface area impairment can be found in those with first-episode SZ,
      but without association with COMT gene polymorphisms. The SPS have more severe
      area impairment than FPS, indicating that SPS and FPS may be attributed to
      different etiological mechanisms.

PMID- 25863101
TI  - [Association of VKORC1 gene -1639G/A polymorphism with atrial fibrillation in
      ethnic Uygurs and Hans from Xinjiang].
AB  - OBJECTIVE: To assess the association of VKORC1 gene -1639G/A polymorphism with
      atrial fibrillation (AF) in ethnic Uygurs and Hans from Xinjiang. METHODS: The
      above polymorphism was detected among 100 Uygur and 102 Han AF patients and 103
      Uygur and 111 Han subjects that have no AF with polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: A
      statistically significant difference was detected between the patient and control
      groups of Uygur origin in terms of genotypic and allelic frequencies (P<0.05).
      Logistic regression analysis also indicated the -1639G/A polymorphism as an
      independent risk factor for AF in Uygur population (OR=2.085, 95% CI: 1.067
      4.072, P=0.031). No similar statistical difference was found between the patient
      and control groups of Han origin (P>0.05). CONCLUSION: The -1639G/A polymorphism
      of VKORC1 gene is associated with AF in the Uygur population but not in Hans.

PMID- 25863102
TI  - [Study on the association of USP8 gene polymorphisms with male infertility in
      ethnic Han Chinese from Sichuan].
AB  - OBJECTIVE: To assess the association of single nucleotide polymorphisms (SNPs) of
      ubiquitin-specific protease 8 gene (USP8) with male infertility among ethnic Han
      Chinese from Sichuan. METHODS: A total of 316 infertile males were recruited
      (case group), which included 72 severe oligozoospermic (SO) cases and 244 non
      obstructive azoospermic (NOA) cases. The control group consisted of 149 fertile
      males. The genotypes of 4 SNPs (rs2241769, rs11857513, rs7174015 and rs3743044)
      were determined with a Sequenom MassArray technique. The frequencies of genotype,
      allele and haploptye were analyzed. RESULTS: No significant difference was
      detected in the allelic or genotypic frequencies of the 4 SNPs between the two
      groups (P>0.05). Based on linkage disequilibrium analysis and haplotype
      construction, the frequency distribution of haplotype CAAG showed a significant
      difference between non-obstructive azoospermic patients and the controls
      (P=0.021). CONCLUSION: The 4 SNPs (rs2241769, rs11857513, rs7174015 and
      rs3743044) of USP8 gene may not be associated with male infertility in ethnic
      Hans from Sichuan. While the haplotype CAAG may be a down-regulating factor for
      the risk of NOA.

PMID- 25863103
TI  - [Notch signaling in bone formation and related skeletal diseases].
AB  - Notch signaling is highly conserved in evolution and regarded as a key factor in
      cell fate determination. It mediates cell-to-cell interactions that are critical
      for embryonic development and tissue renewal, and is involved in the occurrence
      and metastasis of neoplasm. Recent researches have found that such signaling
      plays an important role in modulating the differentiation of chondrocytes,
      osteoblasts and osteoclasts. Dysfunction of Notch signaling can result in many
      skeletal diseases such as bone tumor, disorders of bone development or bone
      metabolism. 

PMID- 25863104
TI  - [Progress in molecular genetic studies of retinitis pigmentosa].
AB  - Retinitis pigmentosa (RP) is a group of inherited disorders which involve
      photoreceptors of the retina and can lead to visual loss. The genetic and
      clinical phenotypes of RP feature high heterogeneity. RP can be divided into
      nonsyndromic and syndromic types, both may feature autosomal dominant, autosomal
      reccesive and X-linked inheritance. So far, many genes have been identified, most
      of which are expressed in the photoreceptors or retinal pigment epithelium. Sixty
      three genes have been identified in nonsyndromic RP. This paper reviews recent
      progress in the research of the genetics of RP. 

PMID- 25863105
TI  - [Advances in research on gastrointestinal cancer-associated long non-coding
      RNAs].
AB  - Long non-coding RNAs (lncRNAs) are a class of non-coding transcripts which are
      greater than 200 nucleotides in length and have a variety of biological
      functions. Studies have found that lncRNAs play an important role in the
      development of gastrointestinal cancers and can affect tumor cell growth,
      angiogenesis, metastasis and drug resistance. This paper has reviewed lncRNAs
      associated with gastrointestinal cancers and explored their roles in the
      occurrence, diagnosis and treatment of gastrointestinal cancers. 

PMID- 25863106
TI  - [A pedigree with Marfan syndrome].

PMID- 25863107
TI  - [Familial cortical myoclonic tremor with epilepsy in a pedigree].

PMID- 25863108
TI  - [Seven patients with congenital finger flexion contracture deformity in a
      family].

PMID- 25863109
TI  - Hemoglobin Constant Spring exhibits prolonged ex vivo stability when assessed by
      HPLC.
AB  - OBJECTIVES: 1) To investigate the presence of hemoglobin Constant Spring (HbCS)
      in a patientwith severe microcytic anemia who had previously been diagnosed with
      alpha thalassemia minor. 2) To assess the stability of HbCS post blood collection
      by high performance liquid chromatography (HPLC). DESIGN AND METHODS: Hemoglobin
      fractionation was performed by HPLC immediately after specimen collection using
      the beta-thalassemia Short Program on the BioRad Variant II. To assess HbCS
      stability, the patient's specimen was re-analyzed over a 17 day period. RESULTS:
      HPLC analysis showed a low abundance peak with chromatographic properties
      consistent with HbCS. Presence of this hemoglobin variant was confirmed by
      electrophoresis and gene sequencing. HbCS remained detectable by HPLC for 17 days
      after specimen collection, with minimal degradation. CONCLUSIONS: Our results
      suggest that HbCS is stable many days after blood collection. Consequently, it is
      not necessary to analyze specimens immediately after collection when assessing
      the potential presence of this hemoglobin variant.

PMID- 25863110
TI  - Study of FibroTest and hyaluronic acid biological variation in healthy volunteers
      and comparison of serum hyaluronic acid biological variation between chronic
      liver diseases of different etiology and fibrotic stage using confidence
      intervals.
AB  - OBJECTIVES: Personalized ranges of liver fibrosis serum biomarkers such as
      FibroTest or hyaluronic acid could be used for early detection of fibrotic
      changes in patients with progressive chronic liver disease. Our aim was to
      generate reliable biological variation estimates for these two biomarkers with
      confidence intervals for within-subject biological variation and reference change
      value. DESIGN AND METHODS: Nine fasting healthy volunteers and 66 chronic liver
      disease patients were included. Biological variation estimates were calculated
      for FibroTest in healthy volunteers, and for hyaluronic acid in healthy
      volunteers and chronic liver disease patients stratified by etiology and liver
      fibrosis stage. RESULTS: In healthy volunteers, within-subject biological
      coefficient of variation (with 95% confidence intervals) and index of
      individuality were 20% (16%-28%) and 0.6 for FibroTest and 34% (27%-47%) and 0.79
      for hyaluronic acid, respectively. Overall hyaluronic acid within-subject
      biological coefficient of variation was similar among non-alcoholic fatty liver
      disease and chronic hepatitis C with 41% (34%-52%) and 45% (39%-55%),
      respectively, in contrast to chronic hepatitis B with 170% (140%-215%).
      Hyaluronic acid within-subject biological coefficients of variation were similar
      between F0-F1, F2 and F3 liver fibrosis stages in non-alcoholic fatty liver
      disease with 34% (25%-49%), 41% (31%-59%) and 34% (23%-62%), respectively, and in
      chronic hepatitis C with 34% (27%-47%), 33% (26%-45%) and 38% (27%-65%),
      respectively. However, corresponding hyaluronic acid indexes of individuality
      were lower in the higher fibrosis stages. CONCLUSION: Non-overlapping confidence
      intervals of biological variation estimates allowed us to detect significant
      differences regarding hyaluronic acid biological variation between chronic liver
      disease subgroups.

PMID- 25863111
TI  - Possible involvement of sphingomyelin in the regulation of the plasma sphingosine
      1-phosphate level in human subjects.
AB  - OBJECTIVES: Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid mediator.
      Although the plasma S1P concentration is reportedly determined by cellular
      components, including erythrocytes, platelets, and vascular endothelial cells,
      the possible involvement of other factors, such as serum sphingomyelin (SM) and
      autotaxin (ATX), remains to be elucidated. DESIGN AND METHODS: We measured S1P
      using high-performance liquid chromatography (HPLC), SM and lysophosphatidic acid
      (LPA) using enzymatic assays, ATX antigen using a two-site enzyme immunoassay,
      and ATX activity using a lysophospholipase D activity assay. To fractionate the
      lipoproteins, plasma samples were separated using fast protein liquid
      chromatography (FPLC) utilizing a Superose 6 column. RESULTS: The plasma S1P
      level was positively correlated with the levels of SM and
      lysophosphatidylcholine, but not with the level of phosphatidylcholine. Although
      SM was present in the very low-density lipoprotein (VLDL) fraction, neither the
      plasma S1P level nor the SM level was affected by feeding. The plasma S1P level
      was negatively correlated with the ATX activity. Although the incubation of 100
      MUmol/L of sphingosylphosphorylcholine (SPC) with the serum resulted in a
      significant increase in the S1P level because of the presence of ATX, the
      physiological concentration of SPC did not mimic this effect. CONCLUSION: The
      plasma S1P level was affected by the serum SM level, while the possibility of ATX
      involvement in the increase in the plasma S1P level was considered to be remote
      at least in healthy human subjects.

PMID- 25863112
TI  - Improve discrimination power of serum markers for diagnosis of cholangiocarcinoma
      using data mining-based approach.
AB  - OBJECTIVE: Cholangiocarcinoma (CCA) is usually fatal because of the absence of
      tests for early detection and lack of effective therapy. Tumor markers with
      adequate diagnostic values are of clinical significance. This study is aimed to
      improve the diagnostic power of serum markers using the computational data mining
      technique to develop a combined diagnostic model that yielded the best diagnostic
      values for CCA. DESIGN AND METHODS: Eight CCA-associated markers-carcinoembryonic
      antigen, carbohydrate antigen 19-9, alkaline phosphatase (ALP), and gamma
      glutamyl transferase, biliary-ALP, mucin5AC, CCA-associated carbohydrate antigen
      (CCA-CA) and CA-S27-were used as the inputs for the C4.5 decision tree
      classification model and the selected model was confirmed by ANN analyses. Eight
      serum markers for CCA were determined in the training set of 85 histologically
      proven-CCA patients and 82 control subjects. The chosen set of combined markers
      that gave the best diagnostic values for CCA was then validated in the testing
      set of 22 CCA patients and 60 controls. RESULTS: A decision tree diagram built by
      the C4.5 algorithm suggested the serial analysis of CCA-CA and ALP for
      distinguishing CCA patients from non-CCA subjects with all diagnostic parameters
      >=95%. The combined tests showed a precise diagnosis in the testing set.
      CONCLUSIONS: The C4.5 model indicates the combined markers of CCA-CA and ALP that
      produced the more precise diagnosis for CCA.

PMID- 25863113
TI  - Stability of lactate and pyruvate in cerebrospinal fluid under typical clinical
      laboratory storage conditions.

PMID- 25863114
TI  - Aeras-sponsored meeting reports: Aerosol TB vaccines, whole mycobacteria cell TB
      vaccines, and prevention of sustained Mycobacterium tuberculosis infection.

PMID- 25863115
TI  - A novel subunit vaccine co-expressing GM-CSF and PCV2b Cap protein enhances
      protective immunity against porcine circovirus type 2 in piglets.
AB  - Porcine circovirus type 2 (PCV2) causes porcine circovirus-associated disease.
      Capsid (Cap) protein of PCV2 is the principal immunogenic protein that induces
      neutralizing antibodies and protective immunity. GM-CSF is an immune adjuvant
      that enhances responses to vaccines. In this study, recombinant baculoviruses Ac
      Cap and Ac-Cap-GM-CSF expressing the Cap protein alone and co-expressing the Cap
      protein and porcine GM-CSF, respectively, were constructed successfully. The
      target proteins were analyzed by western blotting and IFA. Further, these
      proteins were confirmed by electron microscopy, which showed that Cap proteins
      could self-assemble into virus-like particles having diameters of 17-25nm. Animal
      experiments showed that pigs immunized with Cap-GM-CSF subunit vaccine showed
      significantly higher levels of PCV2-specific antibodies and neutralizing
      antibodies than pigs immunized with the Cap subunit vaccine and a commercial
      vaccine (Ingelvac CircoFLEX; P<0.05). After PCV2 wild strain challenged, Pigs
      receiving the Cap-GM-CSF subunit vaccine showed significantly higher average
      daily weight gain after wild-type PCV2 challenge than pigs receiving the other
      three vaccines (P<0.05). None of PCV2 DNA was detected in all immunized animals,
      except control animals immunized with phosphate-buffered saline. These results
      indicated that GM-CSF was a powerful immunoadjuvant for PCV2 subunit vaccines
      because it enhanced humoral immune response and improved immune protection
      against PCV2 infection in pigs. Thus, the novel Cap-GM-CSF subunit vaccine has
      the potential to be used as an effective and safe vaccine candidate against PCV2
      infection. 

PMID- 25863116
TI  - Stability of colistimethate sodium in a disposable elastomeric infusion device.
AB  - Infections of the respiratory tract with Pseudomonas aeruginosa in cystic
      fibrosis patients are frequently treated with colistimethate sodium (CMS). For
      the intravenous administration of CMS a disposable elastomeric pump is a
      convenient option. To date, there are no data available on the chemical stability
      of CMS solutions stored in elastomeric pumps. We evaluated the chemical stability
      of 0.8 mg/mL solutions of CMS by measuring the degradation over a period of 7
      days. Test samples were prepared by diluting CMS with saline solution (0.9%). The
      preparations were transferred to 100-mL elastomeric pumps and stored at 4 
      degrees C. The chemical stability was measured by a high-performance liquid
      chromatography method with UV detection. There was no degradation of CMS (<0.5%
      of CMS present as colistin) for at least 3 day at 4  degrees C, and after 7 days
      all test samples remained chemically stable (<5% of CMS present as colistin).
      Since colistin formed in pharmacy-compounded CMS solutions prior to
      administration may cause toxicity, we advise that the solution should be used
      before the hydrolysis of CMS occurs. Therefore, we recommend that the 0.8 mg/mL
      solution of CMS can be stored for up to 3 days at 4  degrees C in an elastomeric
      pump.

PMID- 25863117
TI  - Development of drug-in-adhesive patch formulations for transdermal delivery of
      fluoxetine: In vitro and in vivo evaluations.
AB  - The aim of this study was to develop drug-in adhesive (DIA) patch formulations
      for the transdermal delivery of fluoxetine (FX). The DIA patch formulations
      containing FX were prepared and optimized with various pressure sensitive
      adhesives, drug contents and enhancers. Among the various formulations, DuroTak
      87-502B-based patch formulation containing 20% (w/w) FX with no enhancer was
      selected for in vivo pharmacokinetic study based on in vitro permeation studies
      using hairless mouse, rat and human cadaver skins. The Cmax of FX after the
      transdermal administration of the optimized patch formulation in rats was 52.38
      ng/ml, and plasma concentration of FX was maintained for 36 h. Moreover, the
      predicted human Css (55.79 ng/ml) and Cmax (27.35 ng/ml) were in good agreement
      with the reported plasma levels (15-55 ng/ml) of oral FX in clinical
      applications. These results suggest that the optimized patch formulation could be
      further developed for clinical applications, providing the therapeutic plasma
      level of FX over an extended period. To the best of our knowledge, our results
      are the first reported in vitro and in vivo data on the preparation and
      optimization of FX-loaded DIA patch, showing its feasibility as an effective
      transdermal delivery system for FX.

PMID- 25863118
TI  - Formulation and development of pH-independent/dependent sustained release matrix
      tablets of ondansetron HCl by a continuous twin-screw melt granulation process.
AB  - The objective of the present study was to develop pH-independent/dependent
      sustained release (SR) tablets of ondansetron HCl dihydrate (OND), a selective 5
      HT3 receptor antagonist that is used for prevention of nausea and vomiting caused
      by chemotherapy, radiotherapy and postoperative treatment. The challenge with the
      OND API is its pH-dependent solubility and relatively short elimination half
      life. Therefore, investigations were made to solve these problems in the current
      study. Formulations were prepared using stearic acid as a binding agent via a
      melt granulation process in a twin-screw extruder. The micro-environmental pH of
      the tablet was manipulated by the addition of fumaric acid to enhance the
      solubility and release of OND from the tablet. The in vitro release study
      demonstrated sustained release for 24h with 90% of drug release in formulations
      using stearic acid in combination with ethyl cellulose, whereas 100% drug release
      in 8h for stearic acid-hydroxypropylcellulose matrices. The formulation release
      kinetics was correlated to the Higuchi diffusion model and a non-Fickian drug
      release mechanism. The results of the present study demonstrated for the first
      time the pH dependent release from hydrophilic-lipid matrices as well as pH
      independent release from hydrophobic-lipid matrices for OND SR tablets
      manufactured by means of a continuous melt granulation technique utilizing a twin
      screw extruder.

PMID- 25863119
TI  - Development of mucoadhesive sprayable gellan gum fluid gels.
AB  - The nasal mucosa provides a potentially good route for local and systemic drug
      delivery. However, the protective feature of the nasal cavity make intranasal
      delivery challenging. The application of mucoadhesive polymers in nasal drug
      delivery systems enhances the retention of the dosage form in the nasal cavity.
      Several groups have investigated using low acyl gellan as a drug delivery vehicle
      but only limited research however, has been performed on high acyl gellan for
      this purpose, despite its properties being more conducive to mucoadhesion. High
      acyl gellan produces highly elastic gels below 60 degrees C which make it
      difficult to spray using a mechanical spray device. Therefore, in this study we
      have tried to address this problem by making fluid gels by introducing a shear
      force during gelation of the gellan polymer. These fluid gel systems contain
      gelled micro-particles suspended in a solution of un-gelled polymer. These
      systems can therefore behave as pourable viscoelastic fluids. In this study we
      have investigated the rheological behavior and mucoadhesion of fluid gels of two
      different types of gellan (high and low acyl) and fluid gels prepared from blends
      of high and low acyl gellan at a 50:50 ratio. The results demonstrated that by
      preparing fluid gels of high acyl gellan, the rheological properties were
      sufficient to spray through a standard nasal spray device. Moreover fluid gels
      also significantly enhance both high acyl and low acyl gellan mucoadhesion
      properties. 

PMID- 25863120
TI  - Olanzapine augments the effect of selective serotonin reuptake inhibitors by
      suppressing GABAergic inhibition via antagonism of 5-HT6 receptors in the dorsal
      raphe nucleus.
AB  - The combination of the selective serotonin reuptake inhibitors (SSRIs) and
      atypical antipsychotic drugs shows better therapeutic efficacy than SSRI
      monotherapy in the treatment of depression. However, the underlying mechanisms
      responsible for the augmenting effects of olanzapine are not fully understood.
      Here, we report that olanzapine enhances the SSRI-induced increase in
      extracellular serotonin (5-HT) levels and antidepressant-like effects by
      inhibiting GABAergic neurons through 5-HT6 receptor antagonism in the dorsal
      raphe nucleus (DRN). In organotypic raphe slice cultures, treatment with
      olanzapine (1-100 MUM) enhanced the increase in extracellular 5-HT levels in the
      presence of fluoxetine (10 MUM) or citalopram (1 MUM). The enhancing effect of
      olanzapine was not further augmented by the GABAA receptor antagonist
      bicuculline. Electrophysiological analysis revealed that olanzapine (50 MUM)
      decreased the firing frequency of GABAergic neurons in acute DRN slices. Among
      many serotonergic agents, the 5-HT6 receptor antagonist SB399885 (1-100 MUM)
      mimicked the effects of olanzapine by enhancing the SSRI-induced increase in
      extracellular 5-HT levels, which was not further augmented by bicuculline or
      olanzapine. SB399885 (50 MUM) also decreased the firing frequency of GABAergic
      neurons in the DRN. In addition, an intraperitoneal administration of SB399885
      (10 mg/kg) to mice significantly enhanced the antidepressant-like effect of a
      subeffective dose of citalopram (3 mg/kg) in the tail-suspension test. These
      results suggest that olanzapine decreases local inhibitory GABAergic tone in the
      DRN through antagonism of 5-HT6 receptors, thereby increasing the activity of at
      least part of serotonergic neurons, which may contribute to the augmentation of
      the efficacy of SSRIs.

PMID- 25863121
TI  - Serotonin6 receptors in the dorsal hippocampus regulate depressive-like behaviors
      in unilateral 6-hydroxydopamine-lesioned Parkinson's rats.
AB  - Preclinical studies indicate both activation and blockade of serotonin6 (5-HT6)
      receptors may produce antidepressant-like effects. Depression is a common symptom
      in Parkinson's disease (PD); however, its pathophysiology is unclear. Here we
      examined whether 5-HT6 receptors in the dorsal hippocampus (DH) involve in the
      regulation of PD-associated depression. Unilateral 6-hydroxydopamine lesions of
      the medial forebrain bundle in rats induced depressive-like responses as measured
      by the sucrose preference and forced swim tests when compared to sham-operated
      rats. In sham-operated rats, intra-DH injection of 5HT6 receptor agonist
      WAY208466 or antagonist SB258585 increased sucrose consumption and decreased
      immobility time, indicating the induction of antidepressant effects. In the
      lesioned rats, WAY208466 also produced antidepressant effects, whereas SB258585
      decreased sucrose consumption and increased immobility time, indicating the
      induction of depressive-like behaviors. Neurochemical results showed that
      WAY208466 did not change dopamine (DA) levels in the medial prefrontal cortex
      (mPFC), DH and habenula, and noradrenaline (NA) levels in the DH and habenula in
      sham-operated rats, and SB258585 increased DA and NA levels in these structures.
      Further, WAY208466 increased DA levels in the mPFC, DH and habenula, and NA level
      in the habenula in the lesioned rats, and SB258585 decreased DA levels in the
      mPFC and habenula. Additionally, the lesion did not change the density of
      neuronal glutamate transporter EAAC1/5-HT6 receptor co-expressing neurons in the
      DH. Compared to sham-operated rats, these findings suggest that the effects of 5
      HT6 receptors in PD-associated depression may be mediated through different
      neurochemical mechanisms, and the DH is an important site involved in these
      effects. 

PMID- 25863123
TI  - Toughness and damage susceptibility in human cortical bone is proportional to
      mechanical inhomogeneity at the osteonal-level.
AB  - Limitations associated with current clinical fracture risk assessment tools
      highlight the need for increased understanding of the fracture mechanisms of the
      bone and, ideally, a means of assessing this in vivo. Being a multi-layered
      hierarchical structure, the overall properties of the bone are dictated by its
      structural and compositional properties over multiple length scales. In this
      study, we investigate the osteonal-, micro- and tissue-level mechanical behaviour
      of cortical bone tissue samples from young and elderly donors through atomic
      force microscope (AFM) cantilever-based nanoindentation, reference point
      microindentation (RPI) and fracture toughness experiments respectively. We
      demonstrate that bone's fracture toughness and crack growth resistance at the
      tissue-level are significantly correlated to damage susceptibility at the micro
      level, and mechanical inhomogeneity between lamellae and interlamellar areas at
      the osteonal-level. In more detail, reduced nanoelasticity inhomogeneity of
      lamellar/interlamellar layers within the osteons correlated to increased
      indentation depth at the micro-level and an overall reduction in crack-growth
      toughness and fracture toughness of the tissue. Our data also suggest that
      deterioration of bone's mechanical properties is expressed concurrently at these
      three levels, and that mechanical inhomogeneity between the principal structural
      units of the cortical tissue holds a key role on bone's toughness behaviour. We
      hypothesise that the reduction in nanoelasticity inhomogeneity is--at least to
      some extent--responsible for the inability of the microstructure to effectively
      adapt to the applied load, e.g. by redistributing strains, in a non-catastrophic
      manner preventing damage formation and propagation. Our hypothesis is further
      supported by synchrotron radiation micro-computed tomography (SRMUCT) data, which
      show that failure of tougher bone specimens is governed by increased deflection
      of the crack path and broadly spread damage around the crack-tip. In contrast,
      shorter and more direct crack paths as well as less-distributed damage were
      evidenced during failure of the weaker specimens. Overall, this multi-scale study
      highlights the importance of elasticity inhomogeneity within the osteon to the
      damage susceptibility and consequently to the fracture resistance of the tissue.

PMID- 25863122
TI  - Development and characterization of a human orthotopic neuroblastoma xenograft.
AB  - Neuroblastoma is a pediatric cancer of the developing sympathoadrenal lineage.
      The tumors are known to develop from the adrenal gland or paraspinal ganglia and
      have molecular and cellular features of sympathetic neurons such as dense core
      vesicles and catecholamine production. Here we present the detailed molecular,
      cellular, genetic and epigenetic characterization of an orthotopic xenograft
      derived from a high-risk stage 4 neuroblastoma patient. Overall, the xenografted
      tumor retained the high risk features of the primary tumor and showed aggressive
      growth and metastasis in the mouse. Also, the genome was preserved with no
      additional copy number variations, structural variations or aneuploidy. There
      were 13 missense mutations identified in the xenograft that were not present in
      the patient's primary tumor and there were no new nonsense mutations. None of the
      missense mutations acquired in the xenograft were in known cancer genes. We also
      demonstrate the feasibility of using the orthotopic neuroblastoma xenograft to
      test standard of care chemotherapy and molecular targeted therapeutics. Finally,
      we optimized a new approach to produce primary cultures of the neuroblastoma
      xenografts for high-throughput drug screening which can be used to test new
      combinations of therapeutic agents for neuroblastoma.

PMID- 25863124
TI  - Expression and clinical significance of genes frequently mutated in small cell
      lung cancers defined by whole exome/RNA sequencing.
AB  - Small cell lung cancer (SCLC) is the most aggressive type of lung cancer. Only
      15% of SCLC patients survive beyond 2 years after diagnosis. Therefore, for the
      improvement of patients' outcome in this disease, it is necessary to identify
      genetic alterations applicable as therapeutic targets in SCLC cells. The purpose
      of this study is the identification of genes frequently mutated and expressed in
      SCLCs that will be targetable for therapy of SCLC patients. Exome sequencing was
      performed in 28 primary tumors and 16 metastatic tumors from 38 patients with
      SCLCs. Expression of mutant alleles was verified in 19 cases by RNA sequencing.
      TP53, RB1 and PTEN were identified as being significantly mutated genes.
      Additional 36 genes were identified as being frequently (>=10%) mutated in SCLCs
      by combining the results of this study and two recent studies. Mutated alleles
      were expressed in 8 of the 36 genes, TMEM132D, SPTA1, VPS13B, CSMD2, ANK2, ASTN1,
      ASPM and FBN3. In particular, the TMEM132D, SPTA1 and VPS13B genes were commonly
      mutated in both early and late stage tumors, primary tumors and metastases, and
      tumors before and after chemotherapy, as in the case of the TP53 and RB1 genes.
      Therefore, in addition to TP53, RB1 and PTEN, TMEM132D, SPTA1 and VPS13B could be
      also involved in SCLC development, with the products from their mutated alleles
      being potential therapeutic targets in SCLC patients. 

PMID- 25863125
TI  - Synergistic interactions among flavonoids and acetogenins in Graviola (Annona
      muricata) leaves confer protection against prostate cancer.
AB  - Phytochemical complexity of plant extracts may offer health-promoting benefits
      including chemotherapeutic and chemopreventive effects. Isolation of 'most-active
      fraction' or single constituents from whole extracts may not only compromise the
      therapeutic efficacy but also render toxicity, thus emphasizing the importance of
      preserving the natural composition of whole extracts. The leaves of Annona
      muricata, commonly known as Graviola, are known to be rich in flavonoids,
      isoquinoline alkaloids and annonaceous acetogenins. Here, we demonstrate
      phytochemical synergy among the constituents of Graviola leaf extract (GLE)
      compared to its flavonoid-enriched (FEF) and acetogenin-enriched (AEF) fractions.
      Comparative quantitation of flavonoids revealed enrichment of rutin (~7-fold) and
      quercetin-3-glucoside (Q-3-G, ~3-fold) in FEF compared to GLE. In vivo
      pharmacokinetics and in vitro absorption kinetics of flavonoids revealed enhanced
      bioavailability of rutin in FEF compared to GLE. However, GLE was more effective
      in inhibiting in vitro prostate cancer proliferation, viability and clonogenic
      capacity compared to FEF. Oral administration of 100mg/kg bw GLE showed ~1.2-fold
      higher tumor growth-inhibitory efficacy than FEF in human prostate tumor
      xenografts although the concentration of rutin and Q-3-G was more in FEF.
      Contrarily, AEF, despite its superior in vitro and in vivo efficacy, resulted in
      death of the mice due to toxicity. Our data indicate that despite lower
      absorption and bioavailability of rutin, maximum efficacy was achieved in the
      case of GLE, which also comprises of other phytochemical groups including
      acetogenins that make up its natural complex environment. Hence, our study
      emphasizes on evaluating the nature of interactions among Graviola leaf
      phytochemcials for developing favorable dose regimen for prostate cancer
      management to achieve optimal therapeutic benefits. 

PMID- 25863126
TI  - Radiation-induced homotypic cell fusions of innately resistant glioblastoma cells
      mediate their sustained survival and recurrence.
AB  - Understanding of molecular events underlying resistance and relapse in
      glioblastoma (GBM) is hampered due to lack of accessibility to resistant cells
      from patients undergone therapy. Therefore, we mimicked clinical scenario in an
      in vitro cellular model developed from five GBM grade IV primary patient samples
      and two cell lines. We show that upon exposure to lethal dose of radiation, a
      subpopulation of GBM cells, innately resistant to radiation, survive and
      transiently arrest in G2/M phase via inhibitory pCdk1(Y15). Although arrested,
      these cells show multinucleated and giant cell phenotype (MNGC). Significantly,
      we demonstrate that these MNGCs are not pre-existing giant cells from parent
      population but formed via radiation-induced homotypic cell fusions among
      resistant cells. Furthermore, cell fusions induce senescence, high expression of
      senescence-associated secretory proteins (SASPs) and activation of pro-survival
      signals (pAKT, BIRC3 and Bcl-xL) in MNGCs. Importantly, following transient non
      proliferation, MNGCs escape senescence and despite having multiple spindle poles
      during mitosis, they overcome mitotic catastrophe to undergo normal cytokinesis
      forming mononucleated relapse population. This is the first report showing
      radiation-induced homotypic cell fusions as novel non-genetic mechanism in
      radiation-resistant cells to sustain survival. These data also underscore the
      importance of non-proliferative phase in resistant glioma cells. Accordingly, we
      show that pushing resistant cells into premature mitosis by Wee1 kinase inhibitor
      prevents pCdk1(Y15)-mediated cell cycle arrest and relapse. Taken together, our
      data provide novel molecular insights into a multistep process of radiation
      survival and relapse in GBM that can be exploited for therapeutic interventions. 

PMID- 25863127
TI  - miR-29c suppresses pancreatic cancer liver metastasis in an orthotopic
      implantation model in nude mice and affects survival in pancreatic cancer
      patients.
AB  - We investigated mechanisms of pancreatic cancer metastasis and defined the
      biological role of miR-29c in pancreatic cancer metastasis. After two rounds of
      cell selection in vivo, pancreatic cancer cells with various metastatic
      potentials derived from spontaneous liver metastases were used as a model of
      pancreatic cancer to determine the role of miR-29c in pancreatic cancer
      metastasis. Pancreatic cancer samples were analyzed for miRNA-29c expression, and
      these levels were associated with survival between groups. miR-29c suppresses
      cell migration and invasion by targeting the MMP2 3'UTR. Overexpression of miR
      29c suppresses pancreatic cancer liver metastasis in a nude mouse orthotopic
      implantation model. miR-29c expression was associated with metastasis and
      pancreatic cancer patient survival. miR-29c plays an important role in mediating
      pancreatic cancer metastasis to the liver by targeting MMP2. Therefore, miR-29c
      may serve as a novel marker of pancreatic cancer metastasis and possibly as a
      therapeutic target to treat pancreatic cancer liver metastasis. 

PMID- 25863128
TI  - Protein trafficking in colorectal carcinogenesis-targeting and bypassing
      resistance to currently applied treatments.
AB  - Membrane receptors constitute novel targets during current treatment of
      metastatic colorectal cancer (CRC) due to the fact that their aberrant
      expression/activity favors cancer cell properties. Protein trafficking is
      responsible for the correct targeting of membrane receptors to the apical and
      basolateral surfaces, as well as to the adherent and tight junctions of the cell.
      Impaired availability or distribution of these receptors along the plasma
      membrane is not only associated with defective cellular homeostasis and tumor
      progression, but also to emerging mechanisms of resistance to CRC-targeted
      therapy. The present review describes how protein trafficking facilitates
      invasion and metastasis of CRC cells and focuses on receptor tyrosine kinases
      (RTKs) endocytic transport, providing thoughts for surpassing RTKs-centered
      mechanisms of resistance. 

PMID- 25863129
TI  - Tumor expression of adiponectin receptor 2 and lethal prostate cancer.
AB  - To investigate the role of adiponectin receptor 2 (AdipoR2) in aggressive
      prostate cancer we used immunohistochemistry to characterize AdipoR2 protein
      expression in tumor tissue for 866 men with prostate cancer from the Physicians'
      Health Study and the Health Professionals Follow-up Study. AdipoR2 tumor
      expression was not associated with measures of obesity, pathological tumor stage
      or prostate-specific antigen (PSA) at diagnosis. However, AdipoR2 expression was
      positively associated with proliferation as measured by Ki-67 expression
      quartiles (P-trend < 0.0001), with expression of fatty acid synthase (P-trend =
      0.001), and with two measures of angiogenesis (P-trend < 0.1). An inverse
      association was observed with apoptosis as assessed by the TUNEL assay (P-trend =
      0.006). Using Cox proportional hazards regression and controlling for age at
      diagnosis, Gleason score, year of diagnosis category, cohort and baseline BMI, we
      identified a statistically significant trend for the association between quartile
      of AdipoR2 expression and lethal prostate cancer (P-trend = 0.02). The hazard
      ratio for lethal prostate cancer for the two highest quartiles, as compared to
      the two lowest quartiles, of AdipoR2 expression was 1.9 (95% confidence interval
      [CI]: 1.2-3.0). Results were similar when additionally controlling for categories
      of PSA at diagnosis and Ki-67 expression quartiles. These results strengthen the
      evidence for the role of AdipoR2 in prostate cancer progression. 

PMID- 25863130
TI  - Cortico-striatal circuits: Novel therapeutic targets for substance use disorders.
AB  - It is widely believed that substance use disorder (SUD) results from both pre
      alterations (vulnerability) and/or post-alterations (drug effects) on cortico
      striatal circuits. These circuits are essential for cognitive control,
      motivation, reward dependent learning, and emotional processing. As such,
      dysfunctions in cortico-striatal circuits are thought to relate to the core
      features of SUD, which include compulsive drug use, loss of the ability to
      control drug intake, and the emergence of negative emotional states (Koob and
      Volkow, 2010. Neuropsychopharmacology 35(1), 217-238). While the brain circuits
      underlying SUD have been studied in human patients largely through imaging
      studies, experiments in animals have allowed researchers to examine the specific
      cell-types within these circuits to reveal their role in behavior relevant to
      SUD. Here, we will review imaging studies on cortico-striatal systems that are
      altered in SUD, and describe animal experiments that relate SUD to specific
      neural projections and cell types within this circuitry. We will end with a
      discussion of novel clinical approaches such as deep brain stimulation (DBS),
      repeated transcranial magnetic stimulation (rTMS), and pharmacological targeting
      of G protein-coupled receptor (GPCR) heteromers that may provide promising
      avenues for modulating these circuits to combat SUD in humans.

PMID- 25863132
TI  - Dopaminergic differentiation of stem cells from human deciduous teeth and their
      therapeutic benefits for Parkinsonian rats.
AB  - Parkinson's disease (PD) is a progressive neurodegenerative disorder caused by
      the loss of nigrostriatal dopaminergic (DAergic) neurons and the depletion of
      striatal dopamine. Here we show that DAergic-neuron-like cells could be
      efficiently induced from stem cells derived from human exfoliated deciduous teeth
      (SHEDs), and that these induced cells had therapeutic benefits in a 6-OHDA
      induced Parkinsonian rat model. In our protocol, EGF and bFGF signaling activated
      the SHED's expression of proneural genes, Ngn2 and Mash1, and subsequent
      treatment with brain-derived neurotrophic factor (BDNF) promoted their maturation
      into DAergic neuron-like SHEDs (dSHEDs). A hypoxic DAergic differentiation
      protocol improved cell viability and enhanced the expression of multiple
      neurotrophic factors, including BDNF, GDNF, NT-3, and HGF. Engrafted dSHEDs
      survived in the striatum of Parkinsonian rats, improved the DA level more
      efficiently than engrafted undifferentiated SHEDs, and promoted the recovery from
      neurological deficits. Our findings further suggested that paracrine effects of
      dSHEDs contributed to neuroprotection against 6-OHDA-induced neurodegeneration
      and to nigrostriatal tract restoration. In addition, we found that the
      conditioned medium derived from dSHEDs protected primary neurons against 6-OHDA
      toxicity and accelerated neurite outgrowth in vitro. Thus, our data suggest that
      stem cells derived from dental pulp may have therapeutic benefits for PD. 

PMID- 25863133
TI  - PlantMirnaT: miRNA and mRNA integrated analysis fully utilizing characteristics
      of plant sequencing data.
AB  - miRNA is known to regulate up to several hundreds coding genes, thus the
      integrated analysis of miRNA and mRNA expression data is an important problem.
      Unfortunately, the integrated analysis is challenging since it needs to consider
      expression data of two different types, miRNA and mRNA, and target relationship
      between miRNA and mRNA is not clear, especially when microarray data is used.
      Fortunately, due to the low sequencing cost, small RNA and RNA sequencing are
      routinely processed and we may be able to infer regulation relationships between
      miRNAs and mRNAs more accurately by using sequencing data. However, no method is
      developed specifically for sequencing data. Thus we developed PlantMirnaT, a new
      miRNA-mRNA integrated analysis system. To fully leverage the power of sequencing
      data, three major features are developed and implemented in PlantMirnaT. First,
      we implemented a plant-specific short read mapping tool based on recent
      discoveries on miRNA target relationship in plant. Second, we designed and
      implemented an algorithm considering miRNA targets in the full intragenic region,
      not just 3' UTR. Lastly but most importantly, our algorithm is designed to
      consider quantity of miRNA expression and its distribution on target mRNAs. The
      new algorithm was used to characterize rice under drought condition using our
      proprietary data. Our algorithm successfully discovered that two miRNAs,
      miRNA1425-5p, miRNA 398b, that are involved in suppression of glucose pathway in
      a naturally drought resistant rice, Vandana. The system can be downloaded at
      https://sites.google.com/site/biohealthinformaticslab/resources. 

PMID- 25863134
TI  - Developmental exposure to bisphenol A (BPA) alters sexual differentiation in
      painted turtles (Chrysemys picta).
AB  - Environmental chemicals can disrupt endocrine signaling and adversely impact
      sexual differentiation in wildlife. Bisphenol A (BPA) is an estrogenic chemical
      commonly found in a variety of habitats. In this study, we used painted turtles
      (Chrysemys picta), which have temperature-dependent sex determination (TSD), as
      an animal model for ontogenetic endocrine disruption by BPA. We hypothesized that
      BPA would override TSD and disrupt sexual development. We incubated farm-raised
      turtle eggs at the male-producing temperature (26 degrees C), randomly assigned
      individuals to treatment groups: control, vehicle control, 17beta-estradiol (E2,
      20ng/g-egg) or 0.01, 1.0, 100MUgBPA/g-egg and harvested tissues at hatch. Typical
      female gonads were present in 89% of the E2-treated "males", but in none of the
      control males (n=35). Gonads of BPA-exposed turtles had varying amounts of
      ovarian-like cortical (OLC) tissue and disorganized testicular tubules in the
      medulla. Although the percentage of males with OLCs increased with BPA dose (BPA
      low=30%, BPA-medium=33%, BPA-high=39%), this difference was not significant
      (p=0.85). In all three BPA treatments, SOX9 patterns revealed disorganized
      medullary testicular tubules and beta-catenin expression in a thickened cortex.
      Liver vitellogenin, a female-specific liver protein commonly used as an exposure
      biomarker, was not induced by any of the treatments. Notably, these results
      suggest that developmental exposure to BPA disrupts sexual differentiation in
      painted turtles. Further examination is necessary to determine the underlying
      mechanisms of sex reversal in reptiles and how these translate to EDC exposure in
      wild populations. 

PMID- 25863131
TI  - Intercellular cross-talk in intracerebral hemorrhage.
AB  - Intracerebral hemorrhage (ICH) is a devastating cerebrovascular disorder with
      high mortality and morbidity. Currently, there are few treatment strategies for
      ICH-induced brain injury. A recent increase in interest in the pathophysiology of
      ICH has led to elucidation of the pathways underlying ICH-induced brain injury,
      pathways where intercellular and hematoma to cell signaling play important roles.
      In this review, we summarize recent advances in ICH research focusing on
      intercellular and hematoma:cell cross-talk related to brain injury and recovery
      after ICH. This article is part of a Special Issue entitled SI: Cell Interactions
      In Stroke. 

PMID- 25863135
TI  - A resistive heating system for homeothermic maintenance in small animals.
AB  - PURPOSE: To develop an MR-compatible resistive heater for temperature maintenance
      of anaesthetized animals. MATERIALS AND METHODS: An MR-compatible resistive
      electrical heater was formed from a tightly-wound twisted pair wire, interfaced
      to a homeothermic maintenance controller. Fat-suppressed images and localized
      spectra were acquired with the twisted pair heater and a near-identical single
      strand heater during operation at maximum power. Data were also acquired in the
      absence of heating to demonstrate the insensitivity of MR to distortions arising
      from the passage of current through the heater elements. The efficacy of
      temperature maintenance was examined by measuring rectal temperature immediately
      following induction of general anesthesia and throughout and after the
      acquisition of a heater artifact-prone image series. RESULTS: Images and spectra
      acquired in the presence and absence of DC current through the twisted pair
      heater were identical whereas the passage of current through the single strand
      wire created field shifts and lineshape distortions. Temperature that is lost
      during anesthesia induction was recovered within approximately 10-20 minutes of
      induction, and a stable temperature is reached as the animal's temperature
      approaches the set target. CONCLUSION: The twisted pair wire heater does not
      interfere with MR image quality and maintains adequate thermal input to the
      animal to maintain body temperature.

PMID- 25863136
TI  - Relaxation enhanced compressed sensing three-dimensional black-blood vessel wall
      MR imaging: Preliminary studies.
AB  - OBJECTIVE: In this study, we sought to investigate the feasibility of a new
      technique termed relaxation enhanced compressed sensing three-dimensional motion
      sensitizing driven equilibrium prepared 3D rapid gradient echo sequence (RECS-3D
      MERGE). MATERIALS AND METHODS: The RECS-3D MERGE sequence consisted of a 3D MERGE
      sequence for imaging, a period of delay time (TD) for relaxation enhancement, and
      a pseudo-centric phase encoding order used for under-sampling acquisition to
      maintain scan efficiency. Seven healthy volunteers and six patients with 40% to
      75% carotid artery stenosis were recruited in this study. Healthy subjects
      underwent 3D MERGE, RECS-3D MERGE and two-dimensional (2D) T1-weighted double
      inversion recovery fast spin echo (T1W DIR-FSE) scans. The signal ratio (SR)
      values of 21 RECS-3D MERGE scans were compared in order to determine the optimal
      scan parameter set of acceleration factor (AF) and delay time (TD) for RECS-3D
      MERGE sequence. Patients then underwent 3D MERGE, RECS-3D MERGE using the
      aforementioned optimal scan parameter set and 2D T1W DIR-FSE scans. Two
      radiologists, blinded to the imaging technique, qualitatively graded each image
      on a six-point ordinal scale. RESULTS: The highest value of SR occurred with the
      scan parameter set of 3-fold AF and 800ms TD. Compared to 3D MERGE, RECS-3D MERGE
      with the parameter set significantly improved the image quality for both healthy
      subjects and patients experiments, while the scan efficiency was not sacrificed.
      And no significant differences were observed in the subjective scores of RECS-3D
      MERGE and 2D T1W DIR-FSE image qualities. CONCLUSION: RECS-3D MERGE technique
      achieved significant improvement in black-blood image quality compared with 3D
      MERGE. And the image quality of this 3D rapid carotid black-blood imaging
      technique is comparable to 2D T1W DIR-FSE while it has much higher scan
      efficiency.

PMID- 25863137
TI  - Brain morphology is individual-specific information.
AB  - The identification of individual differences in brain morphology is important to
      understand the background of individual differences in brain functions. In the
      present study, we investigated whether brain morphology is discernibly different
      among individuals and is personally identifiable information. Using structural
      magnetic resonance imaging data from 215 healthy subjects scanned twice (scan
      interval = 1.0 +/- 0.1 years), we performed brain recognition by image
      normalization using a voxel-based morphometry approach, feature extraction based
      on principal component analysis, and calculating the Euclidean distances between
      image pairs projected into the subspace. Even with only 32 dimensions used for
      projection, the rank-one identification rate was 99.5%. With >=112 dimensions
      used, the rank-one identification rate was 100%. At a false accept rate of 0.01%,
      the genuine accept rates were 95.8% and 100% with 32 and >=128 dimensions used
      for projection, respectively. There was little difference in the Euclidean
      distances among different combinations of scanners used or between probe-gallery
      image pairs with and without scanner upgrade. These results indicate that brain
      morphology can identify a specific individual; i.e., brain morphology is
      personally identifiable information. Individually different brain morphology may
      occur as a collection of differences in brain structures that reflect individual
      differences in a variety of performances and various psychological
      characteristics and behavior patterns, and may provide the background of
      individual differences in personality and brain function. 

PMID- 25863138
TI  - Native T1-mapping for non-contrast assessment of myocardial fibrosis in patients
      with hypertrophic cardiomyopathy--comparison with late enhancement
      quantification.
AB  - BACKGROUND: Myocardial fibrosis was shown to influence prognosis in hypertrophic
      cardiomyopathy (HCM). It is typically assessed by late gadolinium enhancement
      (LGE) on cardiac magnetic resonance. Native T1-mapping has been proposed, as a
      contrast-free method of fibrosis assessment. The aim of the study was to define a
      cut-off value for native T1 relaxation time that best reflects LGE quantification
      of myocardial fibrosis. METHODS: In 25 patients with HCM and 20 controls we
      performed T1-mapping pre-contrast using ShMOLLI technique. This was followed by
      LGE assessment in the studied group 10 minutes after gadolinium contrast
      injection. Relative myocardial fibrosis size was calculated for varying T1 time
      thresholds (940-1100 ms) and compared with 6 standard deviations (6SD) method for
      LGE. RESULTS: Median fibrosis size calculated with T1-mapping was insignificantly
      different from LGE only for native T1 time threshold of 1060 ms (p = 0.62). Using
      this threshold, Bland-Altman plots demonstrated very good agreement between
      fibrosis sizes from the two methods (slightly better only for 1080 ms threshold).
      For threshold of 1060 ms we also observed good correlation (rho = 0.73) with LGE
      6SD method (insignificantly better for lower thresholds, best for threshold of
      980 ms-rho = 0.88). In control group with no diagnosis of HCM, fibrosis size <1%
      was reached for thresholds of 1040 ms and higher. CONCLUSION: Native T1-mapping
      can be used for non-contrast assessment of myocardial fibrosis in HCM. The 1060
      ms threshold of the native T1 relaxation time is characterized by the best
      balance between agreement and correlation with fibrosis assessed by LGE 6SD
      method.

PMID- 25863139
TI  - A setup for simultaneous measurement of electrophysiological and psychometric
      temporal encoding in the auditory system.
AB  - BACKGROUND: Simultaneous assessment of psychometric tasks and
      electrophysiological recordings is challenging because each requires specific
      technical and physiological preconditions. Electrophysiological recordings
      require a comparatively long test time duration to gain sufficient signal-to
      noise ratios, whereas test duration of psychometric measurements should be
      limited to prevent challenges to the attention of the subject. In order to
      investigate immediate correlation between both measurements a method is
      described, which combines electrophysiological and psychometrical measurements in
      a single test procedure. The test may be applied to subjects with deficits in
      temporal resolution (e.g. auditory neuropathy spectrum disorder, ANSD). NEW
      METHOD: Auditory steady state responses (ASSR) and a pitch discrimination task
      were combined in a single procedure. The setup employed two short-time ASSR sub
      stimuli with different fixed modulation frequencies but same carrier frequencies
      (signal 1 and 2). Simultaneously to the recording of ASSR, the test subject had
      to determine the signal interval which generated the perception of higher pitch.
      RESULTS: The developed setup was successfully tested by means of an artificial
      EEG signal and in one human subject. ASSR signal as well as pitch discrimination
      performance. COMPARISON WITH EXISTING METHODS: To our knowledge the presented
      method has not yet been described elsewhere. CONCLUSIONS: The feasibility of a
      setup to simultaneously perform a pitch discrimination task and
      electrophysiological measurements was demonstrated for the first time. The method
      provides the facility to apply sinusoidal amplitude modulated stimuli (SAM) with
      jittered modulation period lengths.

PMID- 25863140
TI  - Feasibility study of a game integrating assessment and therapy of tinnitus.
AB  - BACKGROUND: Tinnitus, head and ear noise, is due to maladaptive plastic changes
      in auditory and associated neural networks. Tinnitus has been traditionally
      managed through the use of sound to passively mask or facilitate habituation to
      tinnitus, a process that may take 6-12 months. NEW METHOD: A game-based
      perceptual training method, requiring localisation and selective attention to
      sounds, was developed and customised to the individual's tinnitus perception.
      Eight participants tested the games usability at home. RESULTS: Each participant
      successfully completed 30 min of training, for 20 days, along with daily
      psychoacoustic assessment of tinnitus pitch and loudness. The training period and
      intensity of training appears sufficient to reduce tinnitus handicap. COMPARISON
      WITH EXISTING METHOD(S): The training approach used may be a viable alternative
      to frequency discrimination based training for treating tinnitus (Hoare et al.,
      2014) and a useful tool in exploring learning mechanisms in the auditory system.
      CONCLUSIONS: Integration of tinnitus assessment with therapy in a game is
      feasible, and the method(s) warrant further investigation.

PMID- 25863141
TI  - A brain slice experimental model to study the generation and the propagation of
      focally-induced epileptiform activity.
AB  - The early cellular events that in a brain network lead to seizure generation and
      govern seizure propagation are probably based on different cellular mechanisms.
      Experimental models in which these events can be separately studied would
      contribute to improve our understanding of epilepsy. We recently described an in
      vitro model in entorhinal cortex slices from young rats in which focal seizure
      like discharges (SLDs) can be induced in spatially defined regions and at
      predictable times by local NMDA applications performed in the presence of 4
      amimopyridine (4-AP) and low extracellular Mg(2+). Through the use of single-dual
      cell patch-clamp and field potential recordings, and Ca(2+) imaging from large
      ensembles of neurons, interneurons and astrocytes, we here extend this model to
      entorhinal and temporal cortex slices of rat and mouse brain, providing evidence
      that multiple SLDs exhibiting the typical tonic-clonic discharge pattern can be
      also evoked in these cortical regions by successive NMDA applications.
      Importantly, the temporal cortex is more accessible to viral vector injections
      than the entorhinal cortex: this makes it feasible in the former region the
      selective expression in inhibitory interneurons or principal neurons of
      genetically encoded Ca(2+) indicators (GECI) or light-gated opsins. In this
      model, an optogenetic approach allows to activate specific neuronal types at
      spatially defined locations, i.e., the focus or the propagating region, and at
      precise time, i.e., before or during SLD. The NMDA/4-AP model can, therefore,
      represent a valuable tool to gain insights into the role of specific cell
      populations in seizure generation, propagation and cessation. 

PMID- 25863142
TI  - Specific amplification of bacterial DNA by optimized so-called universal
      bacterial primers in samples rich of plant DNA.
AB  - Universal primers targeting the bacterial 16S-rRNA-gene allow quantification of
      the total bacterial load in variable sample types by qPCR. However, many
      universal primer pairs also amplify DNA of plants or even of archaea and other
      eukaryotic cells. By using these primers, the total bacterial load might be
      misevaluated, whenever samples contain high amounts of non-target DNA. Thus, this
      study aimed to provide primer pairs which are suitable for quantification and
      identification of bacterial DNA in samples such as feed, spices and sample
      material from digesters. For 42 primers, mismatches to the sequence of
      chloroplasts and mitochondria of plants were evaluated. Six primer pairs were
      further analyzed with regard to the question whether they anneal to DNA of
      archaea, animal tissue and fungi. Subsequently they were tested with sample
      matrix such as plants, feed, feces, soil and environmental samples. To this
      purpose, the target DNA in the samples was quantified by qPCR. The PCR products
      of plant and feed samples were further processed for the Single Strand
      Conformation Polymorphism method followed by sequence analysis. The sequencing
      results revealed that primer pair 335F/769R amplified only bacterial DNA in
      samples such as plants and animal feed, in which the DNA of plants prevailed. 

PMID- 25863143
TI  - Sequence variability in the mitochondrial 12S rRNA and tRNA Val genes of Ixodes
      scapularis (Acari: Ixodidae) individuals shown previously to be genetically
      invariant.
AB  - The DNA sequences of the mitochondrial (mt) 12S rRNA and tRNA(Val) genes were
      characterized for 82 blacklegged ticks (Ixodes scapularis) that were genetically
      identical for Domains IV and V of the mt 16S rRNA gene. Thirty-one haplotypes,
      differed in sequence by 1-9 bp, were detected among the 82 ticks. Most nucleotide
      alterations in DNA sequence did not affect the stability of the secondary
      structures of the RNAs. The magnitude of the DNA sequence variation in the mt 12S
      rRNA and tRNA(Val) genes among blacklegged ticks suggests that this region of the
      mitochondrial genome has potential as a genetic marker for examining the
      population genetics and phylogeography of I. scapularis.

PMID- 25863144
TI  - Does DNA methylation regulate metamorphosis? The case of the sea lamprey
      (Petromyzon marinus) as an example.
AB  - Lampreys represent one of the most ancient vertebrate lineages enclosing a
      special interest for genetic and epigenetic studies. The sea lamprey (Petromyzon
      marinus) is an anadromous species that experiences metamorphosis all the way up
      to the adult stage. Although representing a gradual process, metamorphosis in
      this species involves dramatic conversions with regard to physiological together
      with structural body changes preparing individuals for a marine and parasitic
      life; in consequence, multiple gene expression modifications are expected. The
      implications of thyroid hormones and HOX gene expression changes have previously
      been reported in this species and also in other vertebrate species. Nonetheless,
      information lacks on how these genes are regulated in lampreys. We here report
      about the existence of methylation pattern differences between the adult and the
      larvae sea lamprey life cycle stages making use of the Methylation-Sensitive
      Amplified Polymorphism (MSAP) technique. Differentially methylated fragment
      sequencing allowed to establish homologous identities with HOX genes involved in
      morphogenesis, along with genes related to the water balance and to the osmotic
      homoeostasis, all associated to a marine environment adaptation. These results
      provide evidences revealing that DNA methylation plays a role in the epigenetic
      regulation of the P. marinus post-natal development representing a starting point
      for future studies. To the best of our knowledge, this is the first study which
      detects DNA methylation changes associated with metamorphosis in lampreys. 

PMID- 25863145
TI  - Wilms' tumor 1 (re)activation in evidence for both epicardial progenitor and
      endothelial cells for cardiovascular regeneration.

PMID- 25863147
TI  - Analysis on the effect of the distances and inclination angles between human head
      and mobile phone on SAR.
AB  - The aim of this paper is to investigate the effects of the distances between the
      human head and internal cellular device antenna on the specific absorption rate
      (SAR). This paper also analyzes the effects of inclination angles between user
      head and mobile terminal antenna on SAR values. The effects of the metal-glass
      casing of mobile phone on the SAR values were observed in the vicinity of the
      human head model. Moreover, the return losses were investigated in all cases to
      mark antenna performance. This analysis was performed by adopting finite
      difference time-domain (FDTD) method on Computer Simulation Technology (CST)
      Microwave Studio. The results indicate that by increasing the distance between
      the user head and antenna, SAR values are decreased. But the increase in
      inclination angle does not reduce SAR values in all cases. Additionally, this
      investigation provides some useful indication for future design of low SAR mobile
      terminal antenna. 

PMID- 25863146
TI  - Bacterial expression of the phosphodiester-binding site of the cation-independent
      mannose 6-phosphate receptor for crystallographic and NMR studies.
AB  - The cation-independent mannose 6-phosphate receptor (CI-MPR) is a multifunctional
      protein that interacts with diverse ligands and plays central roles in autophagy,
      development, and tumor suppression. By delivering newly synthesized
      phosphomannosyl-containing acid hydrolases from the Golgi to endosomal
      compartments, CI-MPR is an essential component in the generation of lysosomes
      that are critical for the maintenance of cellular homeostasis. The ability of CI
      MPR to interact with ~60 different acid hydrolases is facilitated by its large
      extracellular region, with four out of its 15 domains binding phosphomannosyl
      residues. Although the glycan specificity of CI-MPR has been elucidated, the
      molecular basis of carbohydrate binding has not been determined for two out of
      these four carbohydrate recognition domains (CRD). Here we report expression of
      CI-MPR's CRD located in domain 5 that preferentially binds phosphodiester
      containing glycans. Domain 5 of CI-MPR was expressed in Escherichia coli BL21
      (DE3) cells as a fusion protein containing an N-terminal histidine tag and the
      small ubiquitin-like modifier (SUMO) protein. The His6-SUMO-CRD construct was
      recovered from inclusion bodies, refolded in buffer to facilitate disulfide bond
      formation, and subjected to Ni-NTA affinity chromatography and size exclusion
      chromatography. Surface plasmon resonance analyses demonstrated that the purified
      protein was active and bound phosphorylated glycans. Characterization by NMR
      spectroscopy revealed high quality (1)H-(15)N HSQC spectra. Additionally,
      crystallization conditions were identified and a crystallographic data set of the
      CRD was collected to 1.8A resolution. Together, these studies demonstrate the
      feasibility of producing CI-MPR's CRD suitable for three-dimensional structure
      determination by NMR spectroscopic and X-ray crystallographic approaches. 

PMID- 25863148
TI  - Increased Mortality Rates During Resident Handoff Periods and the Effect of ACGME
      Duty Hour Regulations.
AB  - BACKGROUND: Medical errors occur following handoff-related miscommunication. Data
      regarding the effect on patient-centered outcomes, specifically mortality, are
      lacking. Our objective was to investigate handoff-related mortality and the
      effect of duty-hour regulations. METHODS: Retrospective cohort study of adult
      medical patients at a public, university-affiliated hospital from 2010 to 2012.
      Patients were divided into 2 cohorts: handoff group (discharged within 7 days
      following a change in resident physician team) vs control group (discharged the 3
      weeks of each 4-week rotation before resident service change). The primary
      outcome was unadjusted and adjusted hospital mortality rate. As a secondary
      prespecified analysis, we examined the effect of 2011 Accreditation Council for
      Graduate Medical Education (ACGME) duty-hour changes. RESULTS: Among 23,736
      patients, unadjusted hospital mortality during the handoff group was higher than
      the control group (2.68% vs 2.08%, respectively; P = .007; odds ratio [OR] 1.30;
      95% confidence interval [CI], 1.08-1.57). Following adjustment, this association
      remained statistically significant (adjusted OR 1.34; P = .003; 95% CI, 1.10
      1.62). Similarly, pre-duty-hour unadjusted hospital mortality was higher in the
      handoff group vs control group (2.87% vs 2.01%, respectively; P = .006; OR 1.44;
      95% CI, 1.11-1.86), which remained statistically significant following adjustment
      (adjusted OR 1.50; P = .002; 95% CI, 1.16-1.95). However, this association lost
      statistical significance following duty-hour revision with respect to both
      unadjusted (2.48% vs 2.15%, respectively; P = .30; OR 1.16; 95% CI, 0.88-1.53)
      and adjusted mortality (OR 1.18; P = .26; 95% CI, 0.89-1.56). CONCLUSIONS:
      Resident transition in care was significantly associated with an increase in
      unadjusted and adjusted hospital mortality. Although improved by 2011 ACGME duty
      hour amendments, a trend toward higher mortality remained following resident
      handoff.

PMID- 25863149
TI  - The Health and Economic Burden of Air Pollution.

PMID- 25863150
TI  - Zinc deficiency presenting with necrolytic acral erythema and coma.

PMID- 25863151
TI  - Diagnostic Utility of Food Terminology: Culinary Clues for the Astute
      Diagnostician.

PMID- 25863152
TI  - Life-threatening folic acid deficiency: Diogenes syndrome in a young woman?

PMID- 25863153
TI  - Estimated Glomerular Filtration Rate Within the Normal or Mildly Impaired Range
      and Incident Cardiovascular Disease.
AB  - BACKGROUND: The association between lower estimated glomerular filtration rate
      (eGFR) and incident cardiovascular disease is less clear within the normal or
      mildly impaired range. METHODS: Using the Chronic Kidney Disease EPIdemiology
      collaboration (CKD-EPI) and the Modification of Diet in Renal Disease (MDRD) eGFR
      formulas, we analyzed outpatients >= 22 years old from 2004-2006 with 60
      mL/min/1.73 m(2) < eGFR < 130 mL/min/1.73 m(2), without prior cardiovascular
      disease, and with and without proteinuria. RESULTS: During a median follow-up of
      96 months and > 10 million patient-years of follow-up, 103,506 and 104,315
      cardiovascular events were recorded using CKD-EPI (n = 1,341,400, mean age 49.2
      years, 42.6% male) and MDRD (n = 1,284,762, mean age 50.2 years, 43.4% male)
      formulas, respectively (incident event rates 4.4% and 4.6%, respectively).
      Adjusting for age, sex, and major cardiovascular risk factors, a 10-unit eGFR
      increase was independently associated with a mean decrease of 3.0% and 1.0% in
      incident cardiovascular events, using CKD-EPI and MDRD, respectively (P < .001
      for both), with a sharp decrease in events in the 100-mL/min/1.73 m(2) < eGFR <
      130 mL/min/1.73 m(2) range in the CKD-EPI, but not the MDRD, cohort. Using net
      reclassification analysis, CKD-EPI was more accurate in predicting events than
      MDRD (Net Reclassification Improvement 0.39, P < .001 stratifying patients to
      eGFR deciles and 0.64, P < .001 as a continuous variable). Using both formulas,
      eGFR was predictive of incident cardiovascular disease for patients without
      proteinuria, but not for the 2.4% with proteinuria (P < .001 for interaction).
      CONCLUSION: Higher eGFR is associated with fewer cardiovascular events in adults
      without prior cardiovascular disease and without proteinuria, particularly in the
      100-mL/min/1.73 m(2) < eGFR < 130 mL/min/1.73 m(2) range, indicating that eGFR,
      especially using the CKD-EPI formula, may be an independent risk marker for
      incident cardiovascular disease.

PMID- 25863154
TI  - Extracellular expression of Thermobifida fusca cutinase with pelB signal peptide
      depends on more than type II secretion pathway in Escherichia coli.
AB  - Our previous studies demonstrated that Thermobifida fusca cutinase is released
      into culture medium when expressed without a signal peptide in Escherichia coli,
      and this extracellular expression results from an enhanced membrane permeability
      caused by cutinase's phospholipid hydrolase activity. The present study
      investigated whether this phenomenon would also occur during the expression of
      cutinase fused to pelB signal peptide (pelB-cutinase). Secretion of fusion
      proteins of this type is generally believed to occur via type II secretion
      pathway. The results showed that when pelB-cutinase was expressed in a secB
      knockout strain, which has a defective type II secretion pathway, there was still
      a large amount of cutinase in the culture medium. Additional experiments
      confirmed that the periplasmic and cytoplasmic fractions of the expressing cells
      had hydrolytic activity toward phosphatidyl ethanolamine, and the recombinant
      cells showed correspondingly improved membrane permeability. All these phenomena
      were also observed in the parent E. coli strain. Moreover, the secretion
      efficiency of the inactive cutinase mutant was found to be significantly lower
      than that of pelB-cutinase in the parent E. coli. Based on these results, the
      phospholipid hydrolase activity of pelB-cutinase must play a larger role in its
      extracellular production than does type II secretion pathway. 

PMID- 25863155
TI  - Context-specific differences in fronto-parieto-occipital effective connectivity
      during short-term memory maintenance.
AB  - Although visual short-term memory (VSTM) performance has been hypothesized to
      rely on two distinct mechanisms, capacity and filtering, the two have not been
      dissociated using network-level causality measures. Here, we hypothesized that
      behavioral tasks challenging capacity or distraction filtering would both engage
      a common network of areas, namely dorsolateral prefrontal cortex (dlPFC),
      superior parietal lobule (SPL), and occipital cortex, but would do so according
      to dissociable patterns of effective connectivity. We tested this by estimating
      directed connectivity between areas using conditional Granger causality (cGC).
      Consistent with our prediction, the results indicated that increasing mnemonic
      load (capacity) increased the top-down drive from dlPFC to SPL, and cGC in the
      alpha (8-14Hz) frequency range was a predominant component of this effect. The
      presence of distraction during encoding (filtering), in contrast, was associated
      with increased top-down drive from dlPFC to occipital cortices directly and from
      SPL to occipital cortices directly, in both cases in the beta (15-25Hz) range.
      Thus, although a common anatomical network may serve VSTM in different contexts,
      it does so via specific functions that are carried out within distinct,
      dynamically configured frequency channels. 

PMID- 25863156
TI  - Inhibitory effect of copper nanoparticles on rosin modified surfactant induced
      aggregation of lysozyme.
AB  - Protein aggregation is associated with many serious diseases including
      Parkinson's and Alzheimer's. Protein aggregation is a primary problem related
      with the health of industrial workers who work with the surfactants, metal ions,
      and cosolvents. We have synthesized rosin-based surfactants, i.e., quaternary
      amines of rosin diethylaminoethyl esters (QRMAE), which is an ester of rosin acid
      with polyethylene glycol monomethyl ether. Here, we report the thermal
      aggregation of lysozyme induced by QRMAE at 65  degrees C and pH 7.4 for a given
      time period in which amorphous aggregates are formed and confirm that copper
      nanoparticles have the ability to inhibit QRMAE-induced aggregation compared with
      zinc and silver-nanoparticles. Aggregation experiments was evaluated using
      several spectroscopic methods and dye binding assay, such as turbidity, Rayleigh
      light scattering, 1-anilino-8-naphthalene sulfonate (ANS), Thioflavin T (Th T),
      congo red (CR) and circular dichroism (CD), that was further supported by
      scanning electron microscopy (SEM) and SEM with EDX. The therapeutic use of
      nanoparticles and the fact that rosin possesses excellent film-forming
      properties, and that its derivatives have pharmaceuticals application such as
      micro encapsulation, coating and film forming, it's matrix materials are used for
      sustained and controlled release tablets, renders importance and application to
      the present study.

PMID- 25863157
TI  - A dendrimer-like hyper branched chitosan beads toward fluoride adsorption from
      water.
AB  - The present study reports a novel approach for the preparation of polyamidoamine
      grafted chitosan beads (PAAGCB) via Michael addition followed by protonation of
      PAAGCB to get protonated PAAGCB (H(+)-PAAGCB). Various metal ions viz., Al(3+),
      Ce(3+), La(3+) and Zr(4+) have been loaded onto the PAAGCB in order to get
      respective Al-PAAGCB, Ce-PAAGCB, La-PAAGCB and Zr-PAAGCB. All these sorbents were
      used to remove the fluoride ions from aqueous solution. Ethylenediamine is used
      for amination purpose of chitosan beads through Michael addition. The results
      showed that Zr-PAAGCB was more selective with the maximum defluoridation capacity
      of 17.47 mg/g than the other metal ion loaded chitosan beads. The sorbents were
      characterized using FTIR, XRD, SEM and EDAX. The fluoride sorption was reasonably
      explained using Freundlich and Langmuir isotherm models. The mechanism concerned
      in the adsorption of fluoride ions is by physisorption on heterogeneous materials
      according to the results obtained by fitting the data to various isotherm models.
      Temperature study carried out at 303, 313 and 323K revealed that the adsorption
      process was spontaneous and endothermic in nature. The applicability of the
      sorbents studied has been tested with field sample collected from fluoride
      endemic area.

PMID- 25863158
TI  - Evaluation of antimicrobial effectiveness and dentine mechanical properties after
      use of chemical and natural auxiliary irrigants.
AB  - OBJECTIVE: To evaluate the effect of GSE, NaOCl, CHX and QMix as an antimicrobial
      agents against Enterococcus faecalis and their influence on flexural and ultimate
      tensile strength of root canal dentine. METHODS: Root canals were divided into
      five groups (n=10) according to the substances used: 2.5% NaOCl, 2% CHX, 6.5%
      GSE, Qmix and control group (distilled water) (DW). Final irrigation was done
      with 17% EDTA in all groups, except when DW was used. The number of colony
      forming units was used to evaluate the antimicrobial activity. Dentine beams were
      used to assess the flexural strength after treatment with substances as described
      before (n=10). The UTS was evaluated after the treatment of root dentine
      hourglass shape sections with the same substances (n=30). RESULTS: The lowest
      bacteria contamination was observed for CHX and GSE, while NaOCl and QMix showed
      an intermediate antimicrobial activity (p>0.05). NaOCl and QMix significantly
      reduced the mechanical properties of dentine (flexural strength and UTS) (p<0.05)
      and no statistical difference was found among CHX, GSE and DW (p>0.05).
      CONCLUSION: CHX and GSE were more effective than NaOCl and QMix against E.
      faecalis. Furthermore, they did not harm dentine mechanical properties as
      observed for NaOCl and QMix. CLINICAL SIGNIFICANCE: The use of GSE can be
      recommended for endodontic procedures since it has good antimicrobial activity
      and does not interfere in the mechanical properties of dentine; similarly to CHX.

PMID- 25863159
TI  - Real-time atrial wall imaging during radiofrequency ablation in a porcine model.
AB  - BACKGROUND: Real-time monitoring of radiofrequency (RF) ablation remains
      challenging. OBJECTIVE: We used intravascular ultrasound (IVUS) to describe
      atrial wall changes during RF ablation and to assess the extent of RF-induced
      lesions. METHODS: In 9 piglets, RF and IVUS catheters were coupled and introduced
      into the right atrium. RF applications were performed along the intercaval line.
      Corresponding IVUS images were analyzed. Wall thickness was correlated with
      electrogram (EGM) changes (n = 9) and histology (n = 5). RESULTS: There were 66
      RF applications performed in 57 sites. IVUS provided real-time imaging of the
      atrial wall during RF application in all but 2 sites. IVUS demonstrated
      significant (>20%) and immediate increase in atrial wall thickness in 71.4% of RF
      applications. It showed epicardial or intramyocardial effusion in 30% of cases, 2
      steam pops, 1 intramural hematoma, and 1 thrombus. EGM amplitude decreased and
      thickness increased after RF application than at baseline (2.20 +/- 1.11 to 0.99
      +/- 0.62 mV and 1.34 +/- 0.53 to 1.93 +/- 0.80 mm, respectively; P < .001 for
      each). However, EGM and thickness changes were poorly correlated (r = 0.43; P <
      .05). Histologically and echographically measured thicknesses were correlated (r
      = 0.71; P = .004), but echographic thickness change was not related to
      histological lesion transmurality. CONCLUSION: An IVUS probe coupled to an RF
      catheter can provide relevant real-time imaging of the atrial wall during
      ablation. Although thickness change does not appear as a good predictor of the
      transmural extent, direct visualization and monitoring of RF application may
      provide new information to guide and secure RF ablation.

PMID- 25863160
TI  - An activation-repolarization time metric to predict localized regions of high
      susceptibility to reentry.
AB  - BACKGROUND: Initiation of reentrant ventricular tachycardia (VT) involves complex
      interactions between front and tail of the activation wave. Recent experimental
      work has identified the time interval between S2 repolarization proximal to a
      line of functional block and S2 activation at the adjacent distal side as a
      critical determinant of reentry. OBJECTIVES: We hypothesized that (1) an
      algorithm could be developed to generate a spatial map of this interval ("reentry
      vulnerability index" [RVI]), (2) this would accurately identify a site of reentry
      without the need to actually induce the arrhythmia, and (3) it would be possible
      to generate an RVI map in patients during routine clinical procedures. METHODS:
      An algorithm was developed that calculated RVI between all pairs of electrodes
      within a given radius. RESULTS: The algorithm successfully identified the region
      with increased susceptibility to reentry in an established Langendorff pig heart
      model and the site of reentry and rotor formation in an optically mapped sheep
      ventricular preparation and computational simulations. The feasibility of RVI
      mapping was evaluated during a clinical procedure by coregistering with cardiac
      anatomy and physiology of a patient undergoing VT ablation. CONCLUSION: We
      developed an algorithm to calculate a reentry vulnerability index from intervals
      between local repolarization and activation. The algorithm accurately identified
      the region of reentry in 2 animal models of functional reentry. The clinical
      application was demonstrated in a patient with VT and identified the area of
      reentry without the need of inducing the arrhythmia.

PMID- 25863161
TI  - The procollagen N-proteinases ADAMTS2, 3 and 14 in pathophysiology.
AB  - Collagen fibers are the main components of most of the extracellular matrices
      where they provide a structural support to cells, tissues and organs. Fibril
      forming procollagens are synthetized as individual chains that associate to form
      homo- or hetero-trimers. They are characterized by the presence of a central
      triple helical domain flanked by amino and carboxy propeptides. Although there
      are some exceptions, these two propeptides have to be proteolytically removed to
      allow the almost spontaneous assembly of the trimers into collagen fibrils and
      fibers. While the carboxy-propeptide is mainly cleaved by proteinases from the
      tolloid family, the amino-propeptide is usually processed by procollagen N
      proteinases: ADAMTS2, 3 and 14. This review summarizes the current knowledge
      concerning this subfamily of ADAMTS enzymes and discusses their potential
      involvement in physiopathological processes that are not directly linked to
      fibrillar procollagen processing. 

PMID- 25863162
TI  - Diffusive gradients in thin films for predicting methylmercury bioavailability in
      freshwaters after photodegradation.
AB  - Determination of the dissolved-bioavailable fraction of methylmercury (MeHg) and
      its degradation pathways in freshwaters deserve attention, to further our
      understanding of the potential risk and toxicity of MeHg. Since the
      photodegradation of MeHg is the most important known abiotic process able to
      demethylate MeHg, this study investigated the role of sunlight on MeHg
      bioavailability in freshwater environments. Experiments to calculate
      photodegradation rate constants of MeHg in different types of freshwater in
      combination with experiments to distinguish the labile fraction of MeHg after
      being exposed to sunlight were performed. The ability of diffusive gradients in
      thin films based on polyacrylamide (P-DGT) to assess DGT-labile MeHg during
      photodegradation was successfully tested. First order photodegradation rate
      constants (kpd) of bioavailable MeHg determined in five different types of waters
      with different amount of dissolved organic matter (DOM), were in the range 0.073
      0.254 h(-1), confirming previous findings that once there is DOM in solution,
      which would favour the photodegradation process, the kpd is mainly affected by
      light attenuation. Simulated sunlight seems not to alter the lability of MeHg,
      although photodegradation processes may decrease the concentrations of MeHg,
      contributing to reduce the amount of bioavailable MeHg (i.e. MeHg uptake by DGT).
      However, the quality of DOM, rather than the quantity, plays an important role in
      the bioavailability of MeHg in freshwater.

PMID- 25863163
TI  - Plant uptake, translocation, and return of polycyclic aromatic hydrocarbons via
      fine root branch orders in a subtropical forest ecosystem.
AB  - Fine roots of woody plants are a heterogeneous system differing markedly in
      structure and function. Nevertheless, knowledge about the plant uptake of organic
      pollutants via fine roots is scarce to date. In the present study, plant uptake,
      translocation, and return of polycyclic aromatic hydrocarbons (PAHs) via fine
      roots in a subtropical forest ecosystem were investigated. Levels of Sigma15PAHs
      in different fine root branch orders of Michelia macclurei, Cryptocarya concinna,
      Cryptocarya chinensis, and Canthium dicoccums varied from 5072+/-1419 ng g(-1) to
      6080+/-1656 ng g(-1), 4037+/-410 ng g(-1) to 6101+/-972 ng g(-1), 3308+/-1191 ng
      g(-1) to 4283+/-237 ng g(-1), and 3737+/-800 ng g(-1) to 4895+/-1216 ng g(-1),
      respectively. Overall, concentrations of low-molecular-weight PAHs with 2-3
      aromatic rings were higher than high-molecular-weight PAHs with 4-6 aromatic
      rings in all fine root branch orders. There were obvious translocations of PAHs
      between adjacent branch orders and a net accumulation of PAHs may occur in the
      fourth- and fifth-order roots. The storage of PAHs in the fine root system showed
      an obvious increasing trend along the branch orders ascending for all tree
      species. The return flux of PAHs via fine roots mortality showed an obvious
      decreasing trend with the branch orders ascending across the four tree species.
      Lower order roots contributed greatly to the total PAHs return flux. Our results
      indicated that fine roots turnover is an effective pathway for perennial tree
      species to remove environmental toxicants absorbed into them.

PMID- 25863164
TI  - Lability of copper bound to humic acid.
AB  - Geochemical speciation models generally include the assumption that all metal
      bound to humic acid and fulvic acid (HA, FA) is labile. However, in the current
      study, we determined the presence of a soluble 'non-labile' Cu fraction bound to
      HA extracted from grassland and peat soils. This was quantified by determining
      isotopically-exchangeable Cu (E-value) and EDTA-extraction of HA-bound Cu,
      separated by size-exclusion chromatography (SEC) and assayed by coupled ICP-MS.
      Evidence of time-dependent Cu fixation by HA was found during the course of an
      incubation study (160 d); up to 50% of dissolved HA-bound Cu was not isotopically
      exchangeable. This result was supported by extraction with EDTA where
      approximately 40% of Cu remained bound to HA despite dissolution in 0.05 M Na2
      EDTA. The presence of a substantial non-labile metal fraction held by HA
      challenges the assumption of wholly reversible equilibrium which is central to
      current geochemical models of metal binding to humic substances.

PMID- 25863165
TI  - It is needless to rehydrate archeological samples to extract ancient DNA.

PMID- 25863166
TI  - Transient Expression of Virally Delivered Meganuclease In Planta Generates
      Inherited Genomic Deletions.

PMID- 25863167
TI  - 15 years on the Editorial Board of PEPTIDES.
AB  - In this article, part of an issue of PEPTIDES celebrating the many years of
      dedication of Dr. A.J. Kastin as Editor-in-Chief of the journal, I describe how I
      first met him and how our friendship and collaboration developed. In 1970 I
      joined Dr. A.V. Schally's team at the Endocrine and Polypeptide Laboratories of
      Tulane University and the V.A. Hospital and it was at that time that I met Dr.
      Kastin for the first time. In 1984 I joined Dr. Schally's team for the second
      time and I began publishing part of my research findings in PEPTIDES. Afterward
      many more results from the research work were also published in PEPTIDES. I
      became a member of the Editorial Board of the same journal in 1999. It was going
      to be a very interesting experience. Some of my observations as a reviewer for
      PEPTIDES are described in the present article. Finally, I expressed my warmest
      congratulations to Dr. A.J. Kastin for the outstanding job that he carried out as
      Editor-in-Chief of PEPTIDES. 

PMID- 25863168
TI  - CB1 receptors modulate affective behaviour induced by neuropathic pain.
AB  - Patients suffering from chronic pain are often diagnosed with a psychiatric
      condition, in particular generalized anxiety and major depression. The underlying
      pathomechanisms contributing to this comorbidity, however, are not entirely
      clear. In this manuscript we have focussed on the potential role of the
      cannabinoid receptor CB1, because it is known to modulate neuronal circuits
      contributing to chronic pain states and affective behaviours. For this purpose we
      analysed the consequences of a partial sciatic nerve ligation on anxiety- and
      depression-related behaviours in mice lacking CB1 receptors. Our results show
      that the development of mechanical hypersensitivity was similar in CB1 deficient
      mice and wild type controls. However, CB1 knockouts showed much more pronounced
      behavioural manifestations of anxiety-related behaviours in the light-dark and
      zero-maze tests, sucrose anhedonia, and disturbed home-cage activity. These
      results indicate that the endocannabinoid system affects chronic pain-induced
      mood changes through CB1 receptors.

PMID- 25863169
TI  - Immunologic Network and Response to Intramyocardial CD34+ Stem Cell Therapy in
      Patients With Dilated Cardiomyopathy.
AB  - BACKGROUND: Although stem cell therapy (SCT) is emerging as a potential treatment
      for patients with dilated cardiomyopathy (DCM), clinical response remains
      variable. Our objective was to determine whether baseline differences in
      circulating immunologic and nonimmunologic biomarkers may help to identify
      patients more likely to respond to intramyocardial injection of CD34(+)-based
      SCT. METHODS AND RESULTS: We enrolled from January 3, 2011 to March 5, 2012 37
      patients with longstanding DCM (left ventricular ejection fraction [LVEF] <40%,
      New York Heart Association functional class III) who underwent peripheral CD34(+)
      stem cell mobilization with granulocyte colony-stimulating factor (G-CSF) and
      collection by means of apheresis. CD34(+) cells were labeled with (99m)Tc
      hexamethylpropyleneamine oxime to allow assessment of stem cell retention at 18
      hours. Response to SCT was predefined as an increase in LVEF of >=5% at 3 months.
      The majority (84%) of patients were male with an overall mean LVEF of 27 +/- 7%
      and a median N-terminal pro-B-type natriuretic peptide (NT-proBNP) level of 2,774
      pg/mL. Nineteen patients (51%) were responders to SCT. There was no significant
      difference between responders and nonresponders regarding to age, sex, baseline
      LVEF, NT-proBNP levels, or 6-minute walking distance. With the use of a partial
      least squares (PLS) predictive model, we identified 9 baseline factors that were
      associated with both stem cell response and stem cell retention (mechanistic
      validation). Among the baseline factors positively associated with both clinical
      response and stem cell retention were G-CSF, SDF-1, LIF, MCP-1, and MCP-3. Among
      baseline factors negatively associated with both clinical response and retention
      were IL-12p70, FASL, ICAM-1, and GGT. A decrease in G-CSF at 3-month follow-up
      was also observed in responders compared with nonresponders (P = .02).
      CONCLUSIONS: If further validated, baseline immunologic and nonimmunologic
      biomarkers may help to identify patients with DCM who are more likely to respond
      to CD34(+)-based SCT.

PMID- 25863170
TI  - Immediate and Sustained Effects of 5-Day Transcranial Direct Current Stimulation
      of the Motor Cortex in Phantom Limb Pain.
AB  - The study explored the analgesic effects of transcranial direct current
      stimulation (tDCS) over the motor cortex on postamputation phantom limb pain
      (PLP). Eight subjects with unilateral lower or upper limb amputation and chronic
      PLP were enrolled in a crossover, double-blind, sham-controlled treatment
      program. For 5 consecutive days, anodal (active or sham) tDCS was applied over
      the motor cortex for 15 minutes at an intensity of 1.5 mA. The 5-day treatment
      with active, but not sham, tDCS induced a sustained decrease in background PLP
      and in the frequency of PLP paroxysms, which lasted for 1 week after the end of
      treatment. Moreover, on each day of active tDCS, patients reported an immediate
      PLP relief, along with an increased ability to move their phantom limb. Patients'
      immediate responses to sham tDCS, on the contrary, were variable, marked by an
      increase or decrease of PLP levels from baseline. These results show that a 5-day
      treatment of motor cortex stimulation with tDCS can induce stable relief from PLP
      in amputees. Neuromodulation targeting the motor cortex appears to be a promising
      option for the management of this debilitating neuropathic pain condition, which
      is often refractory to classic pharmacologic and surgical treatments.
      PERSPECTIVE: The study describes sustained and immediate effects of motor cortex
      stimulation by tDCS on postamputation PLP, whose analgesic action seems linked to
      the motor reactivation of the phantom limb. These results are helpful for the
      exploitation of tDCS as a therapeutic tool for the management of neuropathic
      pain.

PMID- 25863171
TI  - Psychometric Properties of the Pain Stages of Change Questionnaire: New Insights
      on the Measurement of Readiness to Change in Adolescents, Mothers, and Fathers.
AB  - There is increasing interest in the measurement of "readiness to change," or
      willingness to engage in a self-management approach to pain coping, as a
      predictor of treatment response in pediatric pain populations. The primary aim of
      the present study was to provide cross-validation of the Pain Stages of Change
      Questionnaire-Adolescent and -Parent versions in a new, independent pediatric
      chronic pain sample by examining aspects of reliability, validity, and
      generalizability of the factor structures identified in the initial validation
      study. Secondary aims were to 1) expand upon previously identified differences
      between the Pain Stages of Change Questionnaire-Adolescent and -Parent versions
      and 2) examine previously unreported aspects of father data. Although slight
      differences emerged, the factor structures identified in the initial validation
      were largely replicated, suggesting that the psychometric properties of the
      measure are robust across pediatric outpatient chronic pain samples. Variability
      between parent and adolescent reports suggests that there may be meaningful
      differences in the interpretation of each measure and that factors other than
      readiness to change may influence response patterns. Findings highlight the need
      for more fine-tuned analyses of the way the construct operates in youth with
      pediatric pain and their parents. PERSPECTIVE: Findings provide further
      validation of the Pain Stages of Change Questionnaire-Adolescent and -Parent
      versions measures in a new outpatient pediatric chronic pain sample. Previously
      uninvestigated father data showed good reliability and patterns of findings
      similar to validated mother reports. Moreover, the study suggests that the
      adolescent and parent versions may function in meaningfully different ways.

PMID- 25863172
TI  - The association between the C282Y and H63D polymorphisms of HFE gene and the risk
      of Parkinson's disease: A meta-analysis.
AB  - Impaired brain iron homeostasis has been considered as an important mechanism in
      Parkinson's diseases (PD). There are indications that C282Y and H63D
      polymorphisms of HFE genes involved in iron metabolism might contribute to the
      pathogenesis of PD in some cases. However, the investigation of the relationship
      between PD and the two polymorphisms had produced contradictory results. We
      performed a meta-analysis to assess the C282Y and H63D polymorphisms of HFE in PD
      susceptibility. PubMed, EMBASE and Web of Science were systematically searched to
      identify relevant researches. The strict selection criteria and exclusion
      standard were applied. Odds ratios (ORs) with 95% confidence intervals (CIs) were
      used to assess the strength of associations. A fixed-effect or random-effect
      model was selected, depending on the results of the heterogeneity test. Fifteen
      studies were included in the meta-analysis (eight studies with 1631 cases and
      4548 controls for C282Y; seven studies with 1192 cases and 4065 controls for
      H63D). For the C282Y polymorphism, significant associations were observed in the
      Recessive model (YY vs CY+CC: OR=0.22, 95% CI=0.09-0.57, P=0.002). This indicated
      that the C282Y polymorphism in HFE might be a potential protective factor for PD.
      However, no significant associations were found for any genetic model for the
      H63D polymorphism, suggesting that the H63D polymorphism might not be associated
      with PD. 

PMID- 25863173
TI  - Emotional conflict processing induce boosted theta oscillation.
AB  - Although previous studies have reported the neural correlates and dynamics of
      emotional conflict processing, the neural oscillatory features of such processing
      remain unclear. The present study uses time-frequency analysis to determine the
      event-related spectral perturbation (ERSP) characteristics underlying emotional
      conflict processing. Our behavioral results replicate previous findings of
      shorter response times and fewer response errors under the congruent condition
      relative to the incongruent condition, indicating a robust interference effect.
      Theta oscillatory activity was larger for the incongruent than for the congruent
      condition over frontal and frontal-central midline areas, reflecting a greater
      need for control under conditions of conflict. Moreover, the theta power
      difference was negatively associated with the RT difference, indicating that
      greater theta power leads to better behavioral performance. The present findings
      provide evidence that the theta oscillation is necessary for the control of
      emotional conflict. 

PMID- 25863174
TI  - Identification of novel phosphatidic acid-binding proteins in the rat brain.
AB  - Phosphatidic acid (PA) is an abundant negatively-charged phospholipid and has
      long been considered to be an important signaling molecule in diverse cellular
      events. Thus, the identification of proteins that specifically interact with PA
      is of considerable interest to understand the regulatory roles of PA. Herein,
      lipid-affinity purification and mass spectrometric analysis reveals 43 proteins,
      19 known and 24 novel, as PA-binding proteins. A lipid-protein overlay assay
      confirmed that GDI1, PACSIN1, and DPYSL2 interact with not only with PA but also
      with other phospholipids. These results might be helpful for deciphering the
      functional effect of PA in the brain. 

PMID- 25863175
TI  - High frequency stimulation of the STN restored the abnormal high-voltage spindles
      in the cortex and the globus pallidus of 6-OHDA lesioned rats.
AB  - Many studies showed that abnormal oscillations in the cortical-basal ganglia loop
      is involved in the pathophysiology of Parkinson's disease (PD). In contrast to
      the well-studied beta synchronization, high-voltage spindles (HVSs), another type
      of abnormal oscillation observed in PD, are neglected. To explore the role of
      subthalamic nucleus-deep brain stimulation (STN-DBS) in HVSs regulation, we
      simultaneously recorded the local field potential (LFP) in the globus pallidus
      (GP) and electrocorticogram (ECoG) in the primary motor cortex(M1) in freely
      moving 6-hydroxydopamine (6-OHDA) lesioned or control rats before, during, and
      after STN-DBS. Consistent with our previous study, HVSs occurrence, duration, and
      relative power and coherence between the M1 cortex and GP increased in 6-OHDA
      lesioned rats. We found that high but not low frequency stimulation restored the
      abnormal HVSs activity and motor deficit. These results suggest that the STN is
      involved in the abnormal oscillation between the M1 cortex and GP. 

PMID- 25863176
TI  - Multiple horizontally acquired genes from fungal and prokaryotic donors encode
      cellulolytic enzymes in the bdelloid rotifer Adineta ricciae.
AB  - The bdelloid rotifer, Adineta ricciae, an anhydrobiotic microinvertebrate,
      exhibits a high rate of horizontal gene transfer (HGT), with as much as 10% of
      its transcriptome being of foreign origin. Approximately 80% of these foreign
      transcripts are involved in metabolic processes, and therefore bdelloids
      represent a useful model for assessing the contribution of HGT to biochemical
      diversity. To validate this concept, we focused on cellulose digestion, an
      unusual activity in animals, which is represented by at least 16 genes encoding
      cellulolytic enzymes in A. ricciae. These genes have been acquired from a variety
      of different donor organisms among the bacteria and fungi, demonstrating that
      bdelloids use diverse genetic resources to construct a novel biochemical pathway.
      A variable complement of the cellulolytic gene set was found in five other
      bdelloid species, indicating a dynamic process of gene acquisition, duplication
      and loss during bdelloid evolution. For example, in A. ricciae, gene duplications
      have led to the formation of three copies of a gene encoding a GH45 family
      glycoside hydrolase, at least one of which encodes a functional enzyme; all three
      of these gene copies are present in a close relative, Adineta vaga, but only one
      copy was found in each of four Rotaria species. Furthermore, analysis of
      expression levels of the cellulolytic genes suggests that a bacterial-origin
      cellobiase is upregulated upon desiccation. In summary, bdelloid rotifers have
      apparently developed cellulolytic functions by the acquisition and domestication
      of multiple foreign genes. 

PMID- 25863177
TI  - Analysis, characterisation and expression of gill-expressed carbonic anhydrase
      genes in the freshwater crayfish Cherax quadricarinatus.
AB  - Changes in water quality parameters such as pH and salinity can have a
      significant effect on productivity of aquaculture species. Similarly, relative
      osmotic pressure influences various physiological processes and regulates
      expression of a number of osmoregulatory genes. Among those, carbonic anhydrase
      (CA) plays a key role in systemic acid-base balance and ion regulation. Redclaw
      crayfish (Cherax quadricarinatus) are unique in their ability to thrive in
      environments with naturally varied pH levels, suggesting unique adaptation to pH
      stress. To date, however, no studies have focused on identification and
      characterisation of CA or other osmoregulatory genes in C. quadricarinatus. Here,
      we analysed the redclaw gill transcriptome and characterized CA genes along with
      a number of other key osmoregulatory genes that were identified in the
      transcriptome. We also examined patterns of gene expression of these CA genes
      when exposed to three pH treatments. In total, 72,382,710 paired end Illumina
      reads were assembled into 36,128 contigs with an average length of 800bp.
      Approximately 37% of contigs received significant BLAST hits and 22% were
      assigned gene ontology terms. Three full length CA isoforms; cytoplasmic CA
      (ChqCAc), glycosyl-phosphatidylinositol-linked CA (ChqCAg), and beta-CA (ChqCA
      beta) as well as two partial CA gene sequences were identified. Both partial CA
      genes showed high similarity to ChqCAg and appeared to be duplicated from the
      ChqCAg. Full length coding sequences of Na(+)/K(+)-ATPase, V-type H(+)-ATPase,
      sarcoplasmic Ca(+)-ATPase, arginine kinase, calreticulin and Cl(-) channel
      protein 2 were also identified. Only the ChqCAc gene showed significant
      differences in expression across the three pH treatments. These data provide
      valuable information on the gill expressed CA genes and their expression patterns
      in freshwater crayfish. Overall our data suggest an important role for the ChqCAc
      gene in response to changes in pH and in systemic acid-base balance in freshwater
      crayfish.

PMID- 25863178
TI  - Identification of differentially expressed microRNAs involved in non-traumatic
      osteonecrosis through microRNA expression profiling.
AB  - Accumulating evidence has recently indicated a vital role of microRNAs (miRNAs)
      in the development of various bone diseases. However, the biological role of
      miRNAs in the pathogenesis of non-traumatic osteonecrosis of femoral head (ONFH)
      has not yet been investigated. The present study aimed to profile the
      differential miRNA expression between non-traumatic ONFH and femoral neck
      fracture and to develop further understanding of the molecular mechanisms
      involved in the pathogenesis of non-traumatic ONFH. Femoral heads from 4 patients
      with non-traumatic ONFH and 4 with femoral neck fracture were used to analyze the
      miRNA expression profiles in bone tissue using the Exiqon miRCURYTM LNA Array
      (v.18.0). The results of miRNA microarray analysis were further confirmed by real
      time quantitative polymerase chain reaction (qPCR). The differentially expressed
      miRNA target genes and signaling pathways involved were predicted by
      bioinformatics analysis. MiRNA microarray chip analysis revealed that 22 miRNAs
      were significantly up-regulated and 17 were significantly down-regulated in the
      non-traumatic ONFH samples compared with the femoral neck fracture samples. The
      real-time qPCR also confirmed the microarray data. Bioinformatics analysis
      demonstrated that toll-like receptor (TLR), neurotrophin and NOD-like receptor
      signaling pathway were most likely to be regulated by these differential miRNAs.
      This miRNA microarray study reveals significant differences in miRNA expression
      between patients with non-traumatic ONFH and those with femoral neck fracture.
      Our data also manifests that the signaling pathways regulated by these
      differentially expressed miRNAs might be important in the pathogenesis of non
      traumatic ONFH.

PMID- 25863179
TI  - Transcriptional response of human umbilical vein endothelial cell to H9N2
      influenza virus infection.
AB  - Endothelial cells are believed to play an important role in response to virus
      infection. Here, we used a microarray technology to study the gene expression
      profile in human umbilical vein endothelial cells at 24h postinfection with H9N2
      viruses or inactivated H9N2 viral particles. The results showed that H9N2 virus
      infection induced an abundance of differential expressed genes, exhibiting a
      transcriptional signature of viral infection. High levels of chemokine gene
      expressions were detected following treatment. Surprisingly, the most
      significantly up-regulated genes were mainly interferon-stimulated genes (ISGs),
      although there was no change in interferon gene expression and interferon protein
      level. We also found that viral particles were more potent than viruses in
      inducing ISGs expression. These results suggest that induction of expression of
      ISGs is mainly dependent on the interaction between viral particles and
      endothelial cells. Our data offer further insight into the interaction between
      endothelial cells and H9N2 influenza viruses. 

PMID- 25863180
TI  - Beliefs about using an outdoor pool: Understanding perceptions of place in the
      context of a recreational environment to improve health.
AB  - Following the Reasoned Action Approach, an online survey of 74 outdoor pool users
      illustrates how a theory-based behavioral analysis can be used to identify
      people's perceptions of a place in their environment. Regression analysis of
      close-ended data demonstrated that intention "to use the outdoor pool next summer
      season" was predicted (R(2)=.636, p<.0001) from the weighted combination of
      attitude (beta=.663, p<.0001) and perceived control (beta=.197, p<.05). The
      importance of attitude suggests that use can be encouraged by addressing
      advantages. The content analysis of open-ended elicitation data revealed that
      users believed that pool use provides physical, social, and emotional advantages
      and could be made easier by modifying facility parameters. Implications for
      promoting and designing public health spaces to attract users to aquatic
      environments and to improve health are discussed.

PMID- 25863181
TI  - Mapping U.S. long-haul truck drivers' multiplex networks and risk topography in
      inner-city neighborhoods.
AB  - This article illustrates how urban inner-city trucking milieux may influence
      STI/BBI/HIV acquisition and transmission risks for U.S. long-haul truckers, as
      well as their social and risk relationships. Using mixed methods, we collected
      ethnoepidemiological and biological data from long-haul truck drivers and their
      risk contacts in inner-city trucking milieux in Atlanta, Georgia, United States.
      Key findings indicate that within the risk-endemic environment of distressed
      inner-city areas, diverse trucking risk milieux can amplify STI/BBI/HIV risk for
      multiplex networks of truckers. Inner-city neighborhood location, short
      geographic distance among risk contacts, and trucker concurrency can potentially
      exacerbate transmission via bridging higher-risk individuals with lower-risk
      populations at disparate geographic and epidemiological locations. 

PMID- 25863182
TI  - Single-molecule PCR analysis of an unstable microsatellite for detecting
      mutations in sperm of mice exposed to chemical mutagens.
AB  - Single-molecule PCR (SM-PCR) analysis of long and repetitive DNA sequences, known
      as expanded simple tandem repeats (ESTRs), has been the most efficient method for
      studying germline mutation induction in endogenous sequences to date. However,
      the long length of these sequences makes mutation detection imprecise and
      laborious, and they have been characterized only in mice. Here, we explore the
      use of unstable microsatellite sequences that can be typed with high precision by
      capillary electrophoresis as alternative loci for detecting germline mutations.
      We screened 24 microsatellite loci across inbred mouse strains and identified
      Mm2.2.1 as the most polymorphic microsatellite locus. We then optimized SM-PCR of
      Mm2.2.1 to detect mutations in sperm. SM-PCR analysis of sperm from untreated
      B6C3F1 and Muta(TM)Mouse samples revealed mutation frequencies that are
      consistent with rates derived from family pedigree analysis (~ 5 * 10(-3)). To
      determine whether this locus can be used to detect chemically induced germline
      mutations, Muta(TM)Mouse males were exposed by oral gavage to a single dose of
      100mg/kg of N-ethyl-N-nitrosourea (ENU) or to 100mg/kg of benzo(a)pyrene (BaP)
      for 28 days alongside vehicle treated controls. Sperm were collected 10 weeks
      post-ENU exposure to sample sperm exposed as spermatogonial stem cells and 6
      weeks post-BaP exposure to sample sperm that were dividing spermatogonia when the
      exposure was terminated. Both treatments resulted in a significant (approximately
      2-fold) increase in mutation frequency in sperm compared to the control animals.
      The work establishes the utility of this microsatellite for studying mutation
      induction in the germ cells of mice. Because microsatellites are found in
      virtually every species, this approach holds promise for other organisms,
      including humans.

PMID- 25863183
TI  - Paternal irradiation perturbs the expression of circadian genes in offspring.
AB  - The circadian system represents a complex network which influences the timing of
      many biological processes. Recent studies have established that circadian
      alterations play an important role in the susceptibility to many human diseases,
      including cancer. Here we report that paternal irradiation in mice significantly
      affects the expression of genes involved in rhythmic processes in their first
      generation offspring. Using microarrays, the patterns of gene expression were
      established for brain, kidney, liver and spleen samples from the non-exposed
      offspring of irradiated CBA/Ca and BALB/c male mice. The most over-represented
      categories among the genes differentially expressed in the offspring of control
      and irradiated males were those involved in rhythmic process, circadian rhythm
      and DNA-dependent regulation of transcription. The results of our study therefore
      provide a plausible explanation for the transgenerational effects of paternal
      irradiation, including increased transgenerational carcinogenesis described in
      other studies. 

PMID- 25863185
TI  - Chlorinated pool attendance, airway epithelium defects and the risks of allergic
      diseases in adolescents: Interrelationships revealed by circulating biomarkers.
AB  - It has been suggested that allergic diseases might be epithelial disorders driven
      by various environmental stressors but the epidemiological evidence supporting
      this concept is limited. In a cross-sectional study of 835 school adolescents
      (365 boys; mean age, 15.5 yr), we measured the serum concentrations of Club cell
      protein (CC16), surfactant-associated protein D (SP-D) and of total and
      aeroallergen-specific IgE. We used the serum CC16/SP-D concentration ratio as an
      index integrating changes in the permeability (SP-D) and secretory function
      (CC16) of the airway epithelium. In both sexes, early swimming in chlorinated
      pools emerged as the most consistent and strongest predictor of low CC16 and
      CC16/SP-D ratio in serum. Among girls, a low CC16/SP-D ratio was associated with
      increased odds (lowest vs. highest tertile) for pet sensitization (OR 2.97, 95%
      CI 1.19-8.22) and for hay fever in subjects sensitized to pollen (OR 4.12, 95% CI
      1.28-14.4). Among boys, a low CC16/SP-D ratio was associated with increased odds
      for house-dust mite (HDM) sensitization (OR 2.01, 95% CI 1.11-3.73), for allergic
      rhinitis in subjects sensitized to HDM (OR 3.52, 95% CI 1.22-11.1) and for asthma
      in subjects sensitized to any aeroallergen (OR 3.38, 95% CI 1.17-11.0), HDM (OR
      5.20, 95% CI 1.40-24.2) or pollen (OR 5.82, 95% CI 1.51-27.4). Odds for allergic
      sensitization or rhinitis also increased with increasing SP-D or decreasing CC16
      in serum. Our findings support the hypothesis linking the development of allergic
      diseases to epithelial barrier defects due to host factors or environmental
      stressors such as early swimming in chlorinated pools.

PMID- 25863184
TI  - Particulate air pollution and circulating biomarkers among type 2 diabetic
      mellitus patients: the roles of particle size and time windows of exposure.
AB  - BACKGROUND: Short-term associations between size-fractionated particulate matter
      (PM) air pollution and circulating biomarkers are not well established,
      especially among diabetes patients. METHODS: We conducted a longitudinal panel
      study involving 6 repeated measurements of 12 circulating biomarkers among 35
      diabetes patients from April to June, 2013 in Shanghai, China. Real-time number
      and mass concentrations of PM with multiple size fractions between 0.25 and 10
      MUm were measured. Linear mixed-effect models were used to explore the
      associations between size-fractionated PM concentrations and blood biomarkers at
      different time windows. RESULTS: Short-term exposure to PM was significantly
      associated with elevated levels of 5 biomarkers of inflammation, 3 biomarkers of
      coagulation and 1 vasoconstrictor. The effects varied considerably by particle
      size and time windows. Overall, PM with smaller size had stronger associations,
      and the most significant size fractions were 0.25-0.40 MUm. Even 2 h exposure to
      PM can lead to a significant increase in biomarkers. The effects on biomarkers of
      inflammation and vasoconstriction were restricted to the first 12h after
      exposure, but the effects on coagulation persisted for 24-72 h. For example, an
      interquartile range increase in 2h average exposure to PM(0.25-0.40) was
      associated with 6-20% increase in biomarkers of inflammation, 19-38% in
      coagulation and 17% in vasoconstriction. PM had a stronger effect among male
      patients than female patients. CONCLUSIONS: Our results provided important
      evidence on the roles of the size and time windows of exposure in the PM-mediated
      effects on circulating biomarkers of inflammation, coagulation and
      vasoconstriction in diabetes patients in China.

PMID- 25863186
TI  - Association of blood lead levels with urinary F2-8alpha isoprostane and 8-hydroxy
      2-deoxy-guanosine concentrations in first-grade Uruguayan children.
AB  - Oxidative stress (OS) is a potential molecular mechanism for lead-induced
      toxicities, yet, we have limited understanding of the relation between low-level
      lead (Pb) exposure and OS, especially in children. This cross-sectional study
      examines the association between blood lead level (BLL) and two OS markers
      urinary F2-8alpha isoprostane or isoprostane (a marker of lipid peroxidation) and
      8-hydroxy-2-deoxy-Guanosine or 8-OH-dG (a marker of DNA damage) in 211 children,
      aged 5-8 years, from Montevideo, Uruguay. The role of dietary intakes of vitamin
      C and zinc in modifying the relation between BLL and OS was also examined. The
      mean (SD) BLL of the study children was 4.7 (2.2) ug/dL, with 30.2% children
      having BLL >=5 ug/dL, the current reference level set by the US Centre for
      Disease Control for identifying, monitoring and management of children with
      elevated BLL. In covariate-adjusted analysis, there was a weak positive
      association between BLL and urinary isoprostane (adjusted for specific gravity)
      [beta=0.09, p<0.1]. No association was found between children's BLL and urinary 8
      OH-dG. Interactions between dietary intakes of vitamin C or zinc and BLL on OS
      biomarkers were not consistent. However, when BLL and vitamin C or BLL and zinc
      were modeled together, BLL was independently associated with isoprostane
      concentration [beta=0.10, p<0.05] but vitamin C or zinc intake was not. These
      findings suggest that there may be a potential adverse effect of BLL on OS in
      children with low-level Pb exposure. There is a need to study the effects of Pb
      on other OS measures, as well as the role of OS in mediating low-level Pb
      toxicity on functional outcomes.

PMID- 25863188
TI  - Facilitation of adipocyte differentiation of 3T3-L1 cells by debrominated
      tetrabromobisphenol A compounds detected in Japanese breast milk.
AB  - Tetrabromobisphenol A (TeBBPA) is widely used type of brominated flame retardant.
      In this study, we newly synthesized materials for the debrominated congeners,
      2,2',6-tribromobisphenol A (TriBBPA), 2,2'-dibromobisphenol A (2,2'-DiBBPA), 2,6
      dibromobisphenol A (2,6-DiBBPA), and 2-monobromobisphenol A (MoBBPA) and
      evaluated the actual extent of contamination with bisphenol A (BPA), TeBBPA and
      debrominated congeners in Japanese breast milk samples. TriBBPA was detected at
      higher levels than that of TeBBPA, while DiBBPA and MoBBPA were detected at lower
      levels than that of TeBBPA. This observation suggested that humans are exposed to
      debrominated congeners, which might cause adverse effects. Contamination of the
      congeners in breast milk was concern about risk infant health, having vulnerable
      defense system. As pilot study by in vitro experiment, we assessed the toxic
      potency of debrominated congeners by studying their effect on adipocyte
      differentiation in 3T3-L1 cells. We observed 2,6-DiBBPA, TriBBPA and TeBBPA
      elevated the lipid accumulation and adipocyte-specific protein 2 expression in a
      manner dependent on the number of substituted bromines. Moreover, PPARgamma
      transcriptional activities increased in a dose-dependent manner in the presence
      of 2,6-DiBBPA and TriBBPA as well as TeBBPA. Our study clarified that TeBBPA and
      its debrominated congeners accumulated in breast milk and the debrominated
      congeners promoted adipocyte differentiation, showing that a comprehensive
      evaluation of the influences of these compounds including the debrominated
      congeners of TeBBPA on health in infants is necessary. 

PMID- 25863187
TI  - Prenatal polycyclic aromatic hydrocarbon (PAH) exposure, antioxidant levels and
      behavioral development of children ages 6-9.
AB  - PURPOSE: Prenatal polycyclic aromatic hydrocarbon (PAH) exposure has been shown
      to increase DNA adduct levels and to affect neurodevelopment. Micronutrients may
      modify the adverse effect of PAH on neurodevelopment. Thus, we examined if
      micronutrient concentrations modified the association between PAH exposure and
      neurodevelopmental outcomes. METHODS: 151 children from a birth cohort who had
      micronutrient concentrations measured in cord blood and completed the Child
      Behavioral Checklist (CBCL), between the ages of 6 and 9 years, were evaluated.
      Prenatal airborne PAH exposure was measured by personal air monitoring. The betas
      and 95% CI for the associations of antioxidant concentrations and PAH exposure
      with each of the outcomes of CBCL raw score and dichotomized standardized T-score
      (based on clinical cutpoints) were estimated, respectively, by multivariable
      poisson and logistic models. RESULTS: Children below the median for alpha
      tocopherol and gamma-tocopherol concentrations, compared to those above, were
      more likely to have thought problems, aggressive behavior and externalizing
      problems (p<0.05). Lower carotenoid concentration was associated with more
      thought problems (MVbeta=0.60, p<0.001) and externalizing problems (MVbeta=0.13,
      p<0.05) for the same contrast. No statistically significant associations were
      observed between retinol concentrations and neurodevelopmental symptoms. Overall,
      no consistent patterns were observed when we examined the interaction between
      antioxidants (e.g., alpha-tocopherol) and PAH in relation to CBCL symptoms (e.g.,
      internalizing and externalizing problems, p<0.05). CONCLUSIONS: Lower alpha
      tocopherol, gamma-tocopherol and carotenoid levels may adversely affect healthy
      neurodevelopment, even after accounting for PAH exposure. Future research to
      confirm these findings are warranted given the importance of identifying
      modifiable factors for reducing harmful PAH effects.

PMID- 25863189
TI  - A comparison of the carcass and meat quality of Martina Franca donkey foals aged
      8 or 12 months.
AB  - The effects of slaughter age (8 vs 12 months) were investigated on meat and
      carcass quality obtained from Martina Franca donkey foals. Sixteen male foals
      were used, eight were slaughtered at 8 months of age with a mean (+/-s.e.) final
      body weight of 101+/-18kg and the remaining 8 foals slaughtered at 12 months of
      age with a mean final body weight of 122+/-13kg. Carcass weight and dressing
      percentage were higher (P<0.05) in older foals. Shear force value was lower
      (P<0.05) in donkeys slaughtered at 8 months of age (54.03N) compared to the same
      muscle Longissimus Thoracis et Lumborum (LTL) collected in older animals
      (62.66N). Muscle glycogen content was higher (P<0.05) in foals slaughtered at
      12months of age. Donkey foal meat showed an interesting content of essential
      amino acids and a notable percentage of unsaturated fatty acids in both groups of
      animals, giving a high nutritional value to this alternative red meat.

PMID- 25863190
TI  - Evaluation of the efficiency of nested q-PCR in the detection of Mycobacterium
      tuberculosis complex directly from tuberculosis-suspected lesions in post-mortem
      macroscopic inspections of bovine carcasses slaughtered in the state of Mato
      Grosso, Brazil.
AB  - Bovine tuberculosis (BTB) is a zoonotic disease caused by Mycobacterium bovis, a
      member of the Mycobacterium tuberculosis complex (MTC). The quick and specific
      detection of this species is of extreme importance, since BTB may cause economic
      impacts, in addition to presenting imminent risks to human health. In the present
      study a nested real-time PCR test (nested q-PCR) was used in post-mortem
      evaluations to assess cattle carcasses with BTB-suspected lesions. A total of
      41,193 cattle slaughtered in slaughterhouses located in the state of Mato Grosso,
      were examined. Of the examined animals, 198 (0.48%) showed BTB-suspected lesions.
      M. bovis was isolated in 1.5% (3/198) of the samples. Multiplex-PCR detected MTC
      in 7% (14/198) of the samples. The nested q-PCR test detected MTC in 28% (56/198)
      of the BTB-suspected lesions, demonstrating higher efficiency when compared to
      the multiplex-PCR and conventional microbiology. Nested q-PCR can therefore be
      used as a complementary test in the national program for control and eradication
      of bovine tuberculosis. 

PMID- 25863191
TI  - Metatarsal strapping tightness effect to vertical jump performance.
AB  - The study investigated the effect of metatarsal strapping on vertical jump
      performance and evaluated the difference in lower limb kinematics and
      electromyographic signal (EMG) between different strapping force levels. Twelve
      male callisthenic athletes completed single vertical jump from a squat posture
      with hands on hips under three conditions as non-strapping (NS), moderate
      strapping (MS) and high strapping (HS) round metatarsals. Ground reaction force
      (GRF) was recorded with KISTLER force platform to calculate the vertical jump
      height. Angles of ankle, knee and hip were measured with VICON motion analysis
      system and EMG data were recorded with mega6000 system. Data showed that jump
      height was significantly higher under HS than NS condition. Compared with NS,
      ankle inversion decreased significantly during take-off and external rotation
      increased significantly during landing with MS. Significant difference was also
      found in the muscle activity of tibialis anterior between non-strapping and
      strapping conditions. 

PMID- 25863192
TI  - Biomonitoring Equivalents for interpretation of urinary fluoride.
AB  - Exposure to fluoride is widespread due to its natural occurrence in the
      environment and addition to drinking water and dental products for the prevention
      of dental caries. The potential health risks of excess fluoride exposure include
      aesthetically unacceptable dental fluorosis (tooth mottling) and increased
      skeletal fragility. Numerous organizations have conducted risk assessments and
      set guidance values to represent maximum recommended exposure levels as well as
      recommended adequate intake levels based on potential public health benefits of
      fluoride exposure. Biomonitoring Equivalents (BEs) are estimates of the average
      biomarker concentrations corresponding to such exposure guidance values. The
      literature on daily urinary fluoride excretion rates as a function of daily
      fluoride exposure was reviewed and BE values corresponding to the available US
      and Canadian exposure guidance values were derived for fluoride in urine. The
      derived BE values range from 1.1 to 2.1mg/L (1.2-2.5MUg/g creatinine).
      Concentrations of fluoride in single urinary spot samples from individuals, even
      under exposure conditions consistent with the exposure guidance values, may vary
      from the predicted average concentrations by several-fold due to within- and
      across-individual variation in urinary flow and creatinine excretion rates and
      due to the rapid elimination kinetics of fluoride. Thus, the BE values are most
      appropriately applied to screen population central tendency estimates for
      biomarker concentrations rather than interpretation of individual spot sample
      concentrations. 

PMID- 25863193
TI  - Increasing Scientific Confidence in Adverse Outcome Pathways: Application of
      Tailored Bradford-Hill Considerations for Evaluating Weight of Evidence.
AB  - Systematic consideration of scientific support is a critical element in
      developing and, ultimately, using adverse outcome pathways (AOPs) for various
      regulatory applications. Though weight of evidence (WoE) analysis has been
      proposed as a basis for assessment of the maturity and level of confidence in an
      AOP, methodologies and tools are still being formalized. The Organization for
      Economic Co-operation and Development (OECD) Users' Handbook Supplement to the
      Guidance Document for Developing and Assessing AOPs (OECD 2014a; hereafter
      referred to as the OECD AOP Handbook) provides tailored Bradford-Hill (BH)
      considerations for systematic assessment of confidence in a given AOP. These
      considerations include (1) biological plausibility and (2) empirical support
      (dose-response, temporality, and incidence) for Key Event Relationships (KERs),
      and (3) essentiality of key events (KEs). Here, we test the application of these
      tailored BH considerations and the guidance outlined in the OECD AOP Handbook
      using a number of case examples to increase experience in more transparently
      documenting rationales for assigned levels of confidence to KEs and KERs, and to
      promote consistency in evaluation within and across AOPs. The major lessons
      learned from experience are documented, and taken together with the case
      examples, should contribute to better common understanding of the nature and form
      of documentation required to increase confidence in the application of AOPs for
      specific uses. Based on the tailored BH considerations and defining questions, a
      prototype quantitative model for assessing the WoE of an AOP using tools of multi
      criteria decision analysis (MCDA) is described. The applicability of the approach
      is also demonstrated using the case example aromatase inhibition leading to
      reproductive dysfunction in fish. Following the acquisition of additional
      experience in the development and assessment of AOPs, further refinement of
      parameterization of the model through expert elicitation is recommended. Overall,
      the application of quantitative WoE approaches hold promise to enhance the rigor,
      transparency and reproducibility for AOP WoE determinations and may play an
      important role in delineating areas where research would have the greatest impact
      on improving the overall confidence in the AOP. 

PMID- 25863194
TI  - Pathogenic mutations causing glucose transport defects in GLUT1 transporter: The
      role of intermolecular forces in protein structure-function.
AB  - Two families of glucose transporter - the Na(+)-dependent glucose cotransporter-1
      (SGLT family) and the facilitated diffusion glucose transporter family (GLUT
      family) - play a crucial role in the translocation of glucose across the
      epithelial cell membrane. How genetic mutations cause life-threatening diseases
      like GLUT1-deficiency syndrome (GLUT1-DS) is not well understood. In this review,
      we have combined previous functional data with our in silico analyses of the
      bacterial homologue of GLUT members, XylE (an outward-facing, partly occluded
      conformation) and previously proposed GLUT1 homology model (an inward-facing
      conformation). A variety of native and mutant side chain interactions were
      modeled to highlight the potential roles of mutations in destabilizing protein
      protein interaction hence triggering structural and functional defects. This
      study sets the stage for future studies of the structural properties that mediate
      GLUT1 dysfunction and further suggests that both SGLT and GLUT families share
      conserved domains that stabilize the transporter structure/function via a similar
      mechanism. 

PMID- 25863195
TI  - Cyanohydrin reactions enhance glycolytic oscillations in yeast.
AB  - Synchronous metabolic oscillations can be induced in yeast by addition of glucose
      and removal of extracellular acetaldehyde (ACAx). Compared to other means of ACAx
      removal, cyanide robustly induces oscillations, indicating additional cyanide
      reactions besides ACA to lactonitrile conversion. Here, (13)C NMR is used to
      confirm our previous hypothesis, that cyanide directly affects glycolytic fluxes
      through reaction with carbonyl-containing compounds. Intracellularly, at least 3
      cyanohydrins were identified. Extracellularly, all signals could be identified
      and lactonitrile was found to account for ~66% of total cyanide removal.
      Simulations of our updated computational model show that intracellular cyanide
      reactions increase the amplitude of oscillations and that cyanide addition lowers
      [ACA] instantaneously. We conclude that cyanide provides the following means of
      inducing global oscillations: a) by reducing [ACAx] relative to oscillation
      amplitude, b) by targeting multiple intracellular carbonyl compounds during
      fermentation, and c) by acting as a phase resetting stimulus. 

PMID- 25863196
TI  - Nanoparticles as synthetic vaccines.
AB  - As vaccines have transitioned from the use of whole pathogens to only the
      required antigenic epitopes, unwanted side effects have been decreased, but
      corresponding immune responses have been greatly diminished. To enhance
      immunogenicity, a variety of controlled release vehicles have been proposed as
      synthetic vaccines, but nanoparticles have emerged as particularly impressive
      systems due to many exciting publications. In specific, nanoparticles have been
      shown capable of not only desirable vaccine release, but can also be targeted to
      immune cells of interest, loaded with immunostimulatory substances termed
      adjuvants, or even induce desirable immune activating effects on their own. In
      the present review, recent advances in the utilization of inorganic, polymeric,
      and biomolecular nanoparticles as synthetic vaccines are discussed. 

PMID- 25863197
TI  - Phenomenon of leptin resistance in seasonal animals: the failure of leptin action
      in the brain.
AB  - The core of the leptin resistance hypothesis promulgated several years ago to
      explain obesity as a result of environmental causes consists of 2 tenets: the
      extinction of leptin-induced intracellular signaling downstream of leptin binding
      to the long form of the neuronal receptor LTRb in the hypothalamus and the
      impedance to leptin entry imposed at the blood-brain barrier (BBB). A recent
      comprehensive investigation concluded that a central leptin insufficiency
      associated with obesity can be attributed to a decreased efficiency of BBB leptin
      transport and not to leptin insensitivity within the hypothalamus. Interestingly,
      anorectic leptin's effects are counteracted in some individuals by a natural
      resistance associated with hyperleptinemia, which is related to changes in
      hypothalamic sensitivity to leptin (eg, due to malnutrition, obesity, or seasonal
      variations due to day-length-dependent reproduction changes). In sheep, it has
      been observed that the hypothalamus is resistant to leptin in some periods, which
      is related to the adaptation of these animals to annual changes in energy supply
      and demand. However, a broad range of ambiguities exists regarding the
      implications that the intracellular signaling of signal transducer and activator
      of transcription-2/suppressor of cytokine signaling 3 (STAT2/SOCS3) imparts
      central leptin resistance. Furthermore, several plausible alternative
      possibilities have been proposed, such as compensatory functional and anatomic
      reorganizations in the appetite regulating network, rearrangements in the
      afferent hormonal feedback signaling involved in weight homeostasis, and
      modifications in leptin transport to the hypothalamus across the BBB. Taken
      together, these observations suggest that the contention that impaired
      intracellular signaling downstream of leptin entry into the appetite regulating
      network expedites environmentally induced obesity remains unsubstantiated and
      requires further evidence. Furthermore, pregnancy decreases hypothalamic
      sensitivity to leptin (or other unknown mechanisms), and lactation can also alter
      the appetite-suppressing central activity of leptin. The objective of this review
      was to offer an approach to understanding (1) how information regarding
      nutritional status is transmitted to and interpreted within the hypothalamus in
      animals, with special attention on seasonally breeding animals and (2) whether
      central leptin resistance and/or leptin insufficiency in the hypothalamus favors
      the development of obesity.

PMID- 25863198
TI  - Lipid accumulation by NaCl induction at different growth stages and
      concentrations in photoautotrophic two-step cultivation of Monoraphidium
      dybowskii LB50.
AB  - NaCl induction in photoautotrophic two-step cultivation is very promising, but
      time node and concentration are critical to the entire production. In this study
      Monoraphidium dybowskii LB50 was subjected to different NaCl concentrations at
      different growth phases. Results showed that during the initial phase (IP), fixed
      carbon was used for sugar and lipid under 5gL(-1) NaCl induction, as well as for
      protein under 10gL(-1) NaCl induction. At late-exponential growth phase (LEGP),
      the highest lipid productivity was obtained at 20gL(-1) NaCl. At stationary phase
      (SP) the highest lipid productivity was also under 20gL(-1) NaCl but lower than
      that of LEGP. In summary, lipid content and quality were improved at all growth
      phases under NaCl induction. Therefore, cultivation scale can be sued to
      determine the time node and dosage of the inducer, thereby realizing the economic
      efficiency of the fundamental guarantee in photoautotrophic two-step cultivation.

PMID- 25863199
TI  - Electrochemical detoxification of phenolic compounds in lignocellulosic
      hydrolysate for Clostridium fermentation.
AB  - Lignocellulosic biomass is being preferred as a feedstock in the biorefinery, but
      lignocellulosic hydrolysate usually contains inhibitors against microbial
      fermentation. Among these inhibitors, phenolics are highly toxic to butyric acid
      producing and butanol-producing Clostridium even at a low concentration. Herein,
      we developed an electrochemical polymerization method to detoxify phenolic
      compounds in lignocellulosic hydrolysate for efficient Clostridium fermentation.
      After the electrochemical detoxification for 10h, 78%, 77%, 82%, and 94% of p
      coumaric acid, ferulic acid, vanillin, and syringaldehyde were removed,
      respectively. Furthermore, 71% of total phenolics in rice straw hydrolysate were
      removed without any sugar-loss. Whereas the cell growth and metabolite production
      of Clostridium tyrobutyricum and Clostridium beijerinckii were completely
      inhibited in un-detoxified hydrolysate, those in detoxifying rice straw
      hydrolysate were recovered to 70-100% of the control cultures. The
      electrochemical detoxification method described herein provides an efficient
      strategy for producing butanol and butyric acid through Clostridium fermentation
      with lignocellulosic hydrolysate. 

PMID- 25863200
TI  - Below and above boiling point comparison of microwave irradiation and conductive
      heating for municipal sludge digestion under identical heating/cooling profiles.
AB  - This research provides a comprehensive comparison between microwave (MW) and
      conductive heating (CH) sludge pretreatments under identical heating/cooling
      profiles at below and above boiling point temperatures. Previous comparison
      studies were constrained to an uncontrolled or a single heating rate due to lack
      of a CH equipment simulating MW under identical thermal profiles. In this
      research, a novel custom-built pressure-sealed vessel which could simulate MW
      pretreatment under identical heating/cooling profiles was used for CH
      pretreatment. No statistically significant difference was proven between MW and
      CH pretreatments in terms of sludge solubilization, anaerobic biogas yield and
      organics biodegradation rate (p-value>0.05), while statistically significant
      effects of temperature and heating rate were observed (p-value<0.05). These
      results explain the contradictory results of previous studies in which only the
      final temperature (not heating/cooling rates) was controlled. 

PMID- 25863201
TI  - Engineering Scheffersomyces stipitis for fumaric acid production from xylose.
AB  - In this work, Scheffersomyces stipitis, the yeast with excellent xylose-utilizing
      ability, was firstly engineered for fumaric acid production from xylose with the
      heterologous reductive pathway from Rhizopus oryzae FM19, and 1.86g/L fumaric
      acid was produced by the initial strain PSRPMF under the oxygen-limited
      condition. Furthermore, three strategies were performed to improve the fumaric
      acid production, including increasing the reductive pathway activity by codon
      optimization, blocking the fumaric acid conversion in tricarboxylic acid cycle by
      knocking out the native fumarases, and improving the fumaric acid transportation
      by overexpressing heterologous transporter. Finally, the strain PSYPMFfS was
      obtained and the fumaric acid titer reached to 4.67g/L, significantly increased
      by 37.92-fold than that of the control strain PSPYSS. It was indicated that the
      S. stipitis was a promising platform for fumaric acid production from xylose. 

PMID- 25863202
TI  - Harvesting green algae from eutrophic reservoir by electroflocculation and post
      use for biodiesel production.
AB  - Each year there are more frequent blooms of green algae and cyanobacteria,
      representing a serious environmental problem of eutrophication.
      Electroflocculation (EF) was studied to harvest the algae which are present in
      reservoirs, as well as different factors which may influence on the effectiveness
      of the process: the voltage applied to the culture medium, run times, electrodes
      separation and natural sedimentation. Finally, the viability of its use to obtain
      biodiesel was studied by direct transesterification. The EF process carried out
      at 10V for 1min, with an electrode separation of 5.5cm and a height of 4cm in
      culture vessel, obtained a recovery efficiency greater than 95%, and octadecenoic
      and palmitic acids were obtained as the fatty acid methyl esters (FAMEs). EF is
      an effective method to harvest green algae during the blooms, obtaining the
      greatest amount of biomass for subsequent use as a source of biodiesel. 

PMID- 25863203
TI  - Investigating the role of feedstock properties and process conditions on products
      formed during the hydrothermal carbonization of organics using regression
      techniques.
AB  - The purpose of this study is to develop regression models that describe the role
      of process conditions and feedstock chemical properties on carbonization product
      characteristics. Experimental data were collected and compiled from literature
      reported carbonization studies and subsequently analyzed using two statistical
      approaches: multiple linear regression and regression trees. Results from these
      analyses indicate that both the multiple linear regression and regression tree
      models fit the product characteristics data well. The regression tree models
      provide valuable insight into parameter relationships. Relative weight analyses
      indicate that process conditions are more influential to the solid yields and
      liquid and gas-phase carbon contents, while feedstock properties are more
      influential on the hydrochar carbon content, energy content, and the normalized
      carbon content of the solid. 

PMID- 25863204
TI  - Improved methane production from brown algae under high salinity by fed-batch
      acclimation.
AB  - Here, a methanogenic microbial community was developed from marine sediments to
      have improved methane productivity from brown algae under high salinity. Fed
      batch cultivation was conducted by adding dry seaweed at 1wt% total solid (TS)
      based on the liquid weight of the NaCl-containing sediment per round of
      cultivation. The methane production rate and level of salinity increased 8-fold
      and 1.6-fold, respectively, at the 10th round of cultivation. Moreover, the rate
      of methane production remained high, even at the 10th round of cultivation, with
      accumulation of salts derived from 10wt% TS of seaweed. The salinity of the 10th
      round culture was equivalent to 5% NaCl. The improved methane production was
      attributed to enhanced acetoclastic methanogenesis because acetate became rapidly
      converted to methane during cultivation. The family Fusobacteriaceae and the
      genus Methanosaeta, the acetoclastic methanogen, predominated in bacteria and
      archaea, respectively, after the cultivation. 

PMID- 25863205
TI  - Effects of operation mode on self-alkalization of high-load denitrifying reactor.
AB  - To study the alkalization issue and its potential effects on high-load
      denitrifying system, the effects of operation mode on self-alkalization of high
      load denitrifying reactor were investigated. The results showed that both the
      increase of substrate concentration and decrease of hydraulic retention time
      (HRT) can induce notable self-alkalization of high-load denitrification reactor
      (with the nitrogen loading rate (NLR) higher than 25kg Nm(-3)d(-1)). The effluent
      pH surpassed the 9.20 when the influent pH value was 7.0+/-0.1. The self
      alkalization of denitrification process originated from the nitrate reduction,
      while the methanol oxidation could alleviate the self-alkalization by
      neutralizing OH(-) and setting up a buffering system of HCO3(-)/CO3(2-). At the
      same NLR, the self-alkalization induced by increase of substrate concentration
      was remarkably stronger than that induced by decrease of HRT. Keeping the nitrate
      concentration below inhibition concentration improved the performance of high
      load reactor and alleviated the self-alkalization. 

PMID- 25863206
TI  - Optimization of chip size and moisture content to obtain high, combined sugar
      recovery after sulfur dioxide-catalyzed steam pretreatment of softwood and
      enzymatic hydrolysis of the cellulosic component.
AB  - The influence of chip size and moisture content on the combined sugar recovery
      after steam pretreatment of lodgepole pine and subsequent enzymatic hydrolysis of
      the cellulosic component were investigated using response surface methodology.
      Chip size had little influence on sugar recovery after both steam pretreatment
      and enzymatic hydrolysis. In contrast, the moisture of the chips greatly
      influenced the relative severity of steam pretreatment and, as a result, the
      combined sugar recovery from the hemicellulosic and cellulosic fractions.
      Irrespective of chip size and the pretreatment temperature, time, and SO2 loading
      that were used, the relative severity of pretreatment was highest at a moisture
      of 30-40w/w%. However, the predictive model indicated that an elevated moisture
      content of roughly 50w/w% (about the moisture content of a standard softwood mill
      chip) would result in the highest, combined sugar recovery (80%) over the widest
      range of steam pretreatment conditions. 

PMID- 25863207
TI  - N-type Cu2O doped activated carbon as catalyst for improving power generation of
      air cathode microbial fuel cells.
AB  - A novel n-type Cu2O doped activated carbon (AC) air cathode (Cu/AC) was developed
      as an alternative to Pt electrode for oxygen reduction in microbial fuel cells
      (MFCs). The maximum power density of MFCs using this novel air cathode was as
      high as 1390+/-76mWm(-2), almost 59% higher than the bare AC air cathode.
      Specifically, the resistance including total resistance and charge transfer
      resistance significantly decreased comparing to the control. Tafel curve also
      showed the faster electro-transfer kinetics of Cu/AC with exchange current
      density of 1.03*10(-3)Acm(-2), which was 69% higher than the control. Ribbon-like
      Cu2O was deposited on the surface of AC with the mesopore surface area
      increasing. Cubic Cu2O crystals exclusively expose (111) planes with the
      interplanar crystal spacing of 2.48A, which was the dominate active sites for
      oxygen reduction reaction (ORR). N-type Cu2O with oxygen vacancies played crucial
      roles in electrochemical catalytic activity. 

PMID- 25863208
TI  - Biodiversity and succession of mycobiota associated to agricultural
      lignocellulosic waste-based composting.
AB  - A comprehensive characterization of the culturable mycobiota associated to all
      stages of lignocellulose-based composting was achieved. A total of 77 different
      isolates were detected, 69 of which were identified on the basis of the 5.8-ITS
      region sequencing. All the isolates were assigned to the phyla Ascomycota and
      Basidiomycota, with prevalence of the Sordariomycetes (19) and Eurotiomycetes
      (17) classes. Penicillium was the most represented genus (11 species), while the
      species Gibellulopsis nigrescens and Microascus brevicaulis were detected at all
      the composting stages and showed the highest relative abundances. Fungal
      diversity decreased as the process proceed, while similarity between fungal
      communities associated to different samples were maximal for those phases closely
      connected chronologically and showing similar biological activity degree. Thus,
      the structure of the lignocellulose-based composting mycobiota can be divided
      into two major stages corresponding to bio-oxidative phase and maturation phase
      together with the final product, with a transitional cooling stage joining both
      of them. 

PMID- 25863209
TI  - Autotrophic nitrogen removal over nitrite in a sponge-bed trickling filter.
AB  - Partial nitritation in sponge-bed trickling filters (STF) under natural air
      circulation was studied in two reactors: STF-1 and STF-2 operated at 30 degrees C
      with sponge thickness of 0.75 and 1.50cm, respectively. The coexistence of
      nitrifiers and Anammox bacteria was obtained and attributed to the favorable
      environment created by the reactors' design and operational regimes. After
      114days of operation, the STF-1 had an average NH4(+)-N removal of 69.3%
      (1.17kgN/m(3)sponged) and a total nitrogen removal of 52.2% (0.88kgN/m(3)sponged)
      at a Nitrogen Loading Rate (NLR) of 1.68kgN/m(3)sponged and Hydraulic Retention
      Time (HRT) of 1.71h. The STF-2 showed an average NH4(+)-N removal of 81.6 %
      (0.77kgN/m(3)sponged) and a total nitrogen removal of 54% (0.51kgN/m(3)sponged),
      at an NLR of 0.95kgN/m(3)sponged and HRT of 2.96h. The findings suggest that
      autotrophic nitrogen removal over nitrite in STF systems is a feasible
      alternative. 

PMID- 25863210
TI  - Facile sand enhanced electro-flocculation for cost-efficient harvesting of
      Dunaliella salina.
AB  - Energy consumption and water resource in the cultivation and harvesting steps
      still need to be minimized for the popularization of the microalgae-based
      products. An efficient electro-flocculation method for harvesting Dunaliella
      Salina integrated with local sand has been successfully applied. Sand was
      effective for speeding up the processes of flocculation and sedimentation of
      algal flocs and the electrolytic hydroxides was essential to bridge the sand and
      small flocs into large dense flocs. The maximal recovery effective improved from
      95.13% in 6min to 98.09% in 4.5min and the optimal electrical energy consumption
      decreased 51.03% compared to conventional electro-flocculation in a laboratory
      ambient condition. Furthermore, reusing the flocculated medium in cultivation of
      the D. Salina with nitrogen supplemented performed no worse than using fresh
      medium. This sand enhanced electro-flocculation (SEF) technology provides a great
      potential for saving time and energy associated with improving microalgae
      harvesting. 

PMID- 25863211
TI  - Enhancement removal of endocrine-disrupting pesticides and nitrogen removal in a
      biofilm reactor coupling of biodegradable Phragmites communis and elastic filler
      for polluted source water treatment.
AB  - The coupling of conventional elastic filler and solid carbon source of Phragmites
      communis (P. communis) as the biofilm support was applied in a biofilm system for
      treating polluted source water containing nitrogen and trace endocrine-disrupting
      pesticides (cypermethrin and chlorpyrifos). Results showed that removal
      efficiencies of TN and EDPs were improved with addition of 3.6kg P. communis/m(3)
      in the biofilm system. Meanwhile, the uniform distribution of P. communis favored
      simultaneously nitrogen and organics removal but not to trace EDPs compared with
      non-uniform distribution of P. communis. The biofilm on elastic filler was mainly
      responsible for the nitrification with NH4(+)-N oxidation efficiency of 82.9+/
      1.5%. Poor nitrification with NH4(+)-N oxidation efficiency of 36.3+/-6.1% but
      effective denitrification with a TN removal efficiency of 56.5+/-2.0% were
      obtained by the biofilm on P. communis. Cypermethrin was mainly removed via
      adsorption and microbial degradation, and chlorpyrifos removal mostly depended on
      the microbial degradation in biofilm system. 

PMID- 25863212
TI  - Performance of three microalgal strains in biogas slurry purification and biogas
      upgrade in response to various mixed light-emitting diode light wavelengths.
AB  - The three microalgal strains were cultivated, namely, Chlorella vulgaris,
      Scenedesmus obliquus, and Neochloris oleoabundans, by applying mixed light
      emitting diode wavelength treatments to biogas slurry in a photobioreactor bag.
      This study aims to compare the growth and nutrient removal efficiency of the
      algae and determine their roles for biogas upgrading. At red:blue=5:5, S.
      obliquus and C. vulgaris efficiently removed COD and TP, respectively. S.
      obliquus demonstrated high N removal efficiency at red:blue=7:3. The same strain
      significantly improved removal capacity for all nutrients compared with C.
      vulgaris and N. oleoabundans, particularly at red:blue=5:5, 7:3, and 3:7. For
      biogas upgrade, CH4 contents were higher than 75% (v/v) for all strains. The
      algae exhibited particularly good CH4 enrichment at red:blue=7:3, 5:5. Results
      show that microalgal biomass production offers real opportunities for addressing
      issues, such as nutrient reduction, CO2 removal, and biogas enrichment. 

PMID- 25863213
TI  - The role of the enzymatic antioxidant system in cylindrospermopsin-induced
      toxicity in human lymphocytes.
AB  - Cylindrospermopsin (CYN) is known to induce cytotoxic effects in eukaryotic cells
      although the exact mechanism underlying these alterations is not fully explained.
      Given that CYN was previously found to decrease the proliferation of human
      lymphocytes through DNA damage and cell cycle arrest followed by an increase in
      the apoptotic rate, the present study evaluated the possible involvement of
      reactive oxygen species (ROS) and oxidative stress in these cytopathic responses.
      The status of enzymatic antioxidants: superoxide dismutase (SOD), glutathione
      peroxidase (GPx) and catalase (CAT) as well as level of lipid peroxidation (LO)
      under CYN influence in human lymphocytes were also studied. It was found that CYN
      exposure (0.01-1.0 MUg/ml) induces a concentration-dependent increase in H2O2
      content within a time as short as 0.5h, reaching its maximum level after 3 and
      6h. The highest H2O2 content was accompanied by a significant decrease of SOD and
      CAT activity and an elevated level of GPx. Moreover, CYN treatment resulted in a
      detectable increase in LO. We conclude that ROS and the products of LO play an
      essential role in CYN-induced toxicity in human lymphocytes. Our study helps to
      elucidate the sequence of events caused by CYN in eukaryotic cells and explain
      the background for previously observed cytopathic responses.

PMID- 25863214
TI  - Hepatotoxicity of piperazine designer drugs: Comparison of different in vitro
      models.
AB  - Piperazine derived drugs emerged on the drug market in the last decade. The aim
      of this study was to investigate in vitro the potential hepatotoxicity of the
      designer drugs N-benzylpiperazine (BZP), 1-(3-trifluoromethylphenyl)piperazine
      (TFMPP), 1-(4-methoxyphenyl)piperazine (MeOPP) and 1-(3,4
      methylenedioxybenzyl)piperazine (MDBP) in two human hepatic cell lines (HepaRG
      and HepG2) and in primary rat hepatocytes. Cell death was evaluated by the MTT
      assay, after 24 h-incubations. Among the tested drugs, TFMPP was the most
      cytotoxic. HepaRG cells and primary hepatocytes revealed to be the most and the
      least resistant cellular models, respectively. To ascertain whether the CYP450
      metabolism could explain their higher susceptibility, primary hepatocytes were co
      incubated with the piperazines and the CYP450 inhibitors metyrapone and
      quinidine, showing that CYP450-mediated metabolism contributes to the
      detoxification of these drugs. Additionally, the intracellular contents of
      reactive species, ATP, reduced (GSH) and oxidized (GSSG) glutathione, changes in
      mitochondrial membrane potential (Deltapsim) and caspase-3 activation were
      further evaluated in primary cells. Overall, an increase in reactive species
      formation, followed by intracellular GSH and ATP depletion, loss of Deltapsim and
      caspase-3 activation was observed for all piperazines, in a concentration
      dependent manner. In conclusion, piperazine designer drugs produce hepatic
      detrimental effects that can vary in magnitude among the different analogues.

PMID- 25863215
TI  - A Thermo-Sensitive Delivery Platform for Topical Administration of Inflammatory
      Bowel Disease Therapies.
AB  - Systemic therapies for inflammatory bowel disease are associated with an
      increased risk of infections and malignancies. Topical therapies reduce systemic
      exposure, but can be difficult to retain or have limited proximal distribution.
      To mitigate these issues, we developed a thermo-sensitive platform, using a
      polymer-based system that is liquid at room temperature but turns into a viscous
      gel on reaching body temperature. After rectal administration to mice with
      dextran sulfate sodium-induced colitis, the platform carrying budesonide or
      mesalamine becomes more viscoelastic near body temperature. Mice given the drug
      containing platform gained more weight and had reduced histologic and biologic
      features of colitis than mice given the platform alone or liquid drugs via enema.
      Image analysis showed that enemas delivered with and without the platform reached
      similar distances in the colons of mice, but greater colonic retention was
      achieved by using the platform. 

PMID- 25863216
TI  - Split-Dose Preparations Are Superior to Day-Before Bowel Cleansing Regimens: A
      Meta-analysis.
AB  - BACKGROUND & AIMS: There are different regimens of preparing the colon for
      colonoscopy, including polyethylene glycol (PEG), sodium phosphate, picosulfate,
      or oral sulfate solutions. We performed a meta-analysis to determine the efficacy
      of split-dose vs other colon preparation regimens, the optimal products for use,
      and the most effective preparation volumes. METHODS: We performed systematic
      searches of MEDLINE, EMBASE, Scopus, CENTRAL, and ISI Web of knowledge databases,
      from January 1980 to March 2014, for published results from randomized trials
      that assessed split-dose regimens vs day-before colonoscopy preparation. We
      excluded studies that included pediatric or hospitalized patients, or patients
      with inflammatory bowel disease. The primary outcome was efficacy of bowel
      cleansing. Secondary outcomes included side effects or complications, outcomes of
      procedures, patients' willingness to repeat the procedure, and the amount of time
      required for patients to resume daily activities. RESULTS: We identified 47
      trials that fulfilled our inclusion criteria (n = 13,487 patients). Split-dose
      preparations provided significantly better colon cleansing than day-before
      preparations (odds ratio [OR], 2.51; 95% confidence interval, 1.86-3.39), as well
      as day-before preparations with PEG (OR, 2.60; 95% confidence interval, 1.46
      4.63), sodium phosphate (OR, 9.34; 95% confidence interval, 2.12-41.11), or
      picosulfate (OR, 3.54; 95% confidence interval, 1.95-6.45). PEG split-dose
      preparations of 3 L or more yielded greater bowel cleanliness than lower-volume
      split-dose regimens (OR, 1.89; 95% confidence interval, 1.01-3.46), but only in
      intention-to-treat analysis. A higher proportion of patients were willing to
      repeat split-dose vs day-before cleansing (OR, 1.90; 95% confidence interval,
      1.05-3.46), and low-volume split-dose preparations vs high-volume split-dose
      preparation (OR, 4.95; 95% confidence interval, 2.21-11.10). There were no
      differences between preparations in other secondary outcome measures. However,
      there was variation among studies in definitions and main and secondary outcomes.
      CONCLUSIONS: Based on meta-analysis, split-dose regimens increase the quality of
      colon cleansing and are preferred by patients compared with day-before
      preparations. Additional research is required to evaluate oral sulfate solution
      based and PEG low-volume regimens further.

PMID- 25863219
TI  - Removing the effects of the "dark matter" in tomography.
AB  - Electron tomography (ET) using different imaging modes has been progressively
      consolidating its position as a key tool in materials science. The fidelity of a
      tomographic reconstruction, or tomogram, is affected by several experimental
      factors. Most often, an unrealistic cloud of intensity that does not correspond
      to a real material phase of the specimen ("dark matter") blurs the tomograms and
      enhances artefacts arising from the missing wedge (MW). Here we show that by
      simple preprocessing of the background level of any tomographic tilt series, it
      is possible to minimise the negative effects of that "dark matter". Iterative
      reconstruction algorithms converge better, leading to tomograms with fewer
      streaking artefacts from the MW, more contrast, and increased accuracy. The
      conclusions are valid irrespective of the imaging mode used, and the methodology
      improves the segmentation and visualisation of tomograms of both crystalline and
      amorphous materials. We show examples of HAADF STEM and BF TEM tomography. 

PMID- 25863218
TI  - Geochemical modelling for predicting the long-term performance of zeolite-PRB to
      treat lead contaminated groundwater.
AB  - The feasibility of using geochemical modelling to predict the performance of a
      zeolite-permeable reactive barrier (PRB) for treating lead (Pb(2+)) contaminated
      water was investigated in this study. A short-term laboratory column experiment
      was first performed with the zeolite (clinoptilolite) until the elution of 50 PV
      (1 PV=ca. 283 mL). Geochemical simulations of the one-dimensional transport of
      the Pb(2+), considering removal processes including: ion-exchange, adsorption and
      complexation; the concomitant release of exchangeable cations (Ca(2+), Mg(2+),
      Na(+), and K(+)) and the changes in pH were subsequently performed using the
      geochemical model PHREEQC. The results showed a reasonable agreement between the
      experimental results and the numerical simulations, with the exception of Ca(2+)
      for which a great discrepancy was observed. The model also indicated the
      formation of secondary mineral precipitates such as goethite and hematite
      throughout the experiment, of which the effect on the hydraulic conductivity was
      found to be negligible. The results were further used to extrapolate the long
      term performance of the zeolite. We found the capacity would be completely
      exhausted at PV=250 (ca. 3 days). The study, thus, generally demonstrates the
      applicability of PHREEQC to predict the short and long-term performance of
      zeolite-PRBs. Therefore, it can be used to assist in the design and for
      management purposes of such barriers.

PMID- 25863217
TI  - Loss of Interstitial Cells of Cajal and Patterns of Gastric Dysrhythmia in
      Patients With Chronic Unexplained Nausea and Vomiting.
AB  - BACKGROUND & AIMS: Chronic unexplained nausea and vomiting (CUNV) is a
      debilitating disease of unknown cause. Symptoms of CUNV substantially overlap
      with those of gastroparesis, therefore the diseases may share pathophysiologic
      features. We investigated this hypothesis by quantifying densities of
      interstitial cells of Cajal (ICCs) and mapping slow-wave abnormalities in
      patients with CUNV vs controls. METHODS: Clinical data and gastric biopsy
      specimens were collected from 9 consecutive patients with at least 6 months of
      continuous symptoms of CUNV but normal gastric emptying who were treated at the
      University of Mississippi Medical Center, and from 9 controls (individuals free
      of gastrointestinal disease or diabetes). ICCs were counted and ultrastructural
      analyses were performed on tissue samples. Slow-wave propagation profiles were
      defined by high-resolution electrical mapping (256 electrodes; 36 cm(2)). Results
      from patients with CUNV were compared with those of controls as well as patients
      with gastroparesis who were studied previously by identical methods. RESULTS:
      Patients with CUNV had fewer ICCs than controls (mean, 3.5 vs 5.6 bodies/field,
      respectively; P < .05), with mild ultrastructural abnormalities in the remaining
      ICCs. Slow-wave dysrhythmias were identified in all 9 subjects with CUNV vs only
      1 of 9 controls. Dysrhythmias included abnormalities of initiation (stable
      ectopic pacemakers, unstable focal activities) and conduction (retrograde
      propagation, wavefront collisions, conduction blocks, and re-entry), operating
      across bradygastric, normal (range, 2.4-3.7 cycles/min), and tachygastric
      frequencies; dysrhythmias showed velocity anisotropy (mean, 3.3 mm/s longitudinal
      vs 7.6 mm/s circumferential; P < .01). ICCs were less depleted in patients with
      CUNV than in those with gastroparesis (mean, 3.5 vs 2.3 bodies/field,
      respectively; P < .05), but slow-wave dysrhythmias were similar between groups.
      CONCLUSIONS: This study defined cellular and bioelectrical abnormalities in
      patients with CUNV, including the identification of slow-wave re-entry.
      Pathophysiologic features of CUNV were observed to be similar to those of
      gastroparesis, indicating that they could be spectra of the same disorder. These
      findings offer new insights into the pathogenesis of CUNV and may help to inform
      future treatments.

PMID- 25863220
TI  - Disease-mongering through clinical trials.
AB  - Our goal in this paper is to articulate a precise concept of at least a certain
      kind of disease-mongering, showing how pharmaceutical marketing can commercially
      exploit certain diseases when their best definition is given through the success
      of a treatment in a clinical trial. We distinguish two types of disease-mongering
      according to the way they exploit the definition of the trial population for
      marketing purposes. We argue that behind these two forms of disease-mongering
      there are two well-known problems in the statistical methodology of clinical
      trials (the reference class problem and the distinction between statistical and
      clinical significance). Overcoming them is far from simple. 

PMID- 25863221
TI  - Adherence and interaction of cationic quantum dots on bacterial surfaces.
AB  - Understanding molecular mechanisms of interactions between nanoparticles and
      bacteria is important and essential to develop nanotechnology for medical and
      environmental applications. Quantum dots (QDs) are specific nanoparticles with
      unique optical properties and high photochemical stability. In the present study,
      direct interactions were observed between cationic QDs and bacteria. Distinct
      fluorescence quenching patterns were developed when cationic QDs interacted with
      Gram negative and Gram positive bacteria. The aggregation of QDs on bacterial
      surface as well as fluorescence quenching depends upon the chemical composition
      and structure of the bacterial cell envelopes. The presence of lipopolysaccharide
      is unique to Gram-negative bacterial surface and provides negatively charge areas
      for absorbing cationic QDs. The effects of lipopolysaccharide were proved on
      fluorescence quenching of cationic QDs. In contrast to Gram-negative bacteria,
      the presence of teichoic acids is unique to Gram-positive bacterial cell wall and
      provides negatively charged sites for cationic QDs along the chain of teichoic
      acid molecules, which may protect QDs from aggregation and fluorescence
      quenching. This study may not only provide insight into behaviors of QDs on
      bacterial cell surfaces but also open a new avenue for designing and applying QDs
      as biosensors in microbiology, medicine, and environmental science. 

PMID- 25863222
TI  - CREKA peptide-conjugated dendrimer nanoparticles for glioblastoma multiforme
      delivery.
AB  - Glioblastoma multiforme (GBM) is the most aggressive central nervous system (CNS)
      tumor because of its fast development, poor prognosis, difficult control and
      terrible mortality. Poor penetration and retention in the glioblastoma parenchyma
      were crucial challenges in GBM nanomedicine therapy. Nanoparticle diameter can
      significantly influence the delivery efficiency in tumor tissue. Decreasing
      nanoparticle size can improve the nanoparticle penetration in tumor tissue but
      decrease the nanoparticle retention effect. Therefore, small nanoparticles with
      high retention effect in tumor are urgently needed for effective GBM drug
      delivery. In present study, a small nanoparticle drug delivery system was
      developed by conjugating fibrin-binding peptide CREKA to Polyamidoamine (PAMAM)
      dendrimer, where PEGylated PAMAM is used as drug carrier due to its small size
      and good penetration in tumor and CREKA is used to target the abundant fibrin in
      GBM for enhanced retention in tumor. In vitro binding ability tests demonstrated
      that CREKA can significantly enhanced nanoparticle binding with fibrin. In vivo
      fluorescence imaging of GBM bearing nude mice, ex vivo brain imaging and frozen
      slices fluorescence imaging further revealed that the CREKA-modified PAMAM
      achieved higher accumulation and deeper penetration in GBM tissue than unmodified
      one. These results indicated that the CREKA-modified PAMAM could penetrate the
      GBM tissue deeply and enhance the retention effect, which was a promising
      strategy for brain tumor therapy. 

PMID- 25863223
TI  - Preparation of ceria-zirconia by modified coprecipitation method and its
      supported Pd-only three-way catalyst.
AB  - A CeO2-ZrO2 compound with mixed phase composition (CZ4) was prepared by modified
      co-precipitation method, and for comparison, single-phase Ce(0.2)Zr(0.8)O2,
      Ce(0.5)Zr(0.5)O2 and Ce(0.8)Zr(0.2)O2 were synthesized via simultaneous co
      precipitation method. The textural, structural and redox properties, together
      with the catalytic performance of the supported Pd-only three-way catalysts were
      investigated systematically. The results revealed that the generation of numerous
      interface sites in Pd/CZ4 due to its mixed phase composition (as confirmed by TEM
      observation) had a positive influence on modifying its structural, redox
      properties and thermal stability. The XRD and Raman results revealed that the
      highest structural stability was obtained by Pd/CZ4 with negligible lattice
      variation and slightest grain growth after aging treatment. The XPS analysis
      demonstrated that the compositional heterogeneity of Pd/CZ4 could facilitate the
      formation of Ce(3+), and was beneficial to preserve high dispersion of Pd as well
      as maintain Pd at a more oxidized state. The H2-TPR and oxygen storage capacity
      measurements indicated that Pd/CZ4 possessed highest reduction ability as well as
      largest oxygen storage capacity regardless of thermal aging treatment. And
      consequently Pd/CZ4 exhibited improved three-way catalytic activity compared with
      the catalysts supported on single-phase Ce(x)Zr(1-x)O2 both before and after
      thermal aging treatment.

PMID- 25863224
TI  - Au nanoparticle clusters from deposition of a coalescing emulsion.
AB  - HYPOTHESIS: Nanoparticle adsorption at the oil-water interface in an unstable,
      coalescing emulsion leads to cluster formation. EXPERIMENTS: Stable suspensions
      of clusters are prepared using a facile, two-step procedure involving few
      reagents and neither thiolated compounds nor chlorinated solvents. First,
      colloidal gold nanoparticles are assembled at the aqueous-hexanol interface in an
      emulsion that rapidly coalesces and spontaneously deposits a film on the interior
      surface of the glass container. The film is dissolved in ethanol with sonication
      to disperse the clusters. The film and clusters are characterized by transmission
      electron and atomic force microscopies as well as ultraviolet-visible
      spectrometry. FINDINGS: Clusters are observed to contain as few as 8 to as many
      as 24 Au nanoparticles. The clusters are anisotropic and can also be formed from
      larger nanoparticles. Hydrophobic and hydrophilic interactions are implicated in
      the formation of these clusters within the interfacial tension gradients of a
      coalescing emulsion. The clusters can be re-suspended in ethanol and water,
      maximizing the utility of these clusters with an extinction band in the near
      Infrared region of the electromagnetic spectrum.

PMID- 25863225
TI  - A method for estimating (41)Ar, (85)(,88)Kr and (131m,133)Xe doses to non-human
      biota.
AB  - A method is presented for estimating (41)Ar, (85,88)Kr and (131m,133)Xe dose
      rates to terrestrial wildlife without having to resort to comparisons with
      analogue radionuclides. The approach can be used to calculate the dose rates
      arising from external exposures to given ambient air concentrations of these
      isotopes. Dose conversion coefficient (DCC) values for a range of representative
      organisms are calculated, using a Monte Carlo approach to generate absorbed
      fractions based on representing animals as reference ellipsoid geometries. Plume
      immersion is the main component of the total DCC. DCC values calculated for a
      human-sized organism are compared with human dose conversion factors from ICRP
      Publication 119, demonstrating the consistency of the biota approach with that
      for humans. An example of application is provided for hypothetical nuclear power
      plant atmospheric discharges with associated exposures to birds and insects. In
      this example, the dose rates appear to be dominated by (133)Xe and (88)Kr,
      respectively. The biota considered would be protected from the effects of noble
      gas radiation from a population protection perspective. 

PMID- 25863226
TI  - Worker Exposure and High Time-Resolution Analyses of Process-Related
      Submicrometre Particle Concentrations at Mixing Stations in Two Paint Factories.
AB  - The paint and coatings industry is known to have significant particulate matter
      (PM) emissions to the atmosphere. However, exposure levels are not studied in
      detail especially when considering submicrometre (PM1) and ultrafine particles
      (particle diameter below 100nm). The evidence is increasing that pulmonary
      exposures to these size fractions are potentially very harmful. This study
      investigates particle emissions during powder handling and paint mixing in two
      paint factories at two mixing stations in each factory. In each case measurements
      were made simultaneously at the mixing station (near-field; NF), as well as at 5
      15 m distance into the workroom far-field (FF), and in the workers breathing
      zone. Particle concentrations (5nm to 30 um) were measured using high time
      resolution particle instruments and gravimetrically using PM1 cyclone filter
      samplers. The PM1 filters were also characterized by scanning electron microscopy
      (SEM). The NF particle and dust concentration levels were linked to pouring
      powder and were used to characterize the emissions and efficiencies of localized
      controls. NF particle number concentrations were 1000-40000cm(-3) above FF
      concentrations. NF particles were mainly between 100 and 500nm and emissions
      appeared to occur in short bursts. Personal PM1 exposure levels varied between
      0.156 and 0.839mg m(-3) and were 1.6-15 times higher than stationary NF PM1
      concentrations. SEM results verified that the personal exposure and NF particles
      were strongly dominated by the pigments and fillers used. Better understanding of
      the entire temporal personal exposure could be improved by using real-time
      particle monitors for personal exposure measurements. This study provides better
      insight into PM exposure characteristics and concentration levels in the paint
      industry.

PMID- 25863227
TI  - Episodic future thinking reduces delay discounting and energy intake in children.
AB  - Discounting of larger future rewards in favor of smaller immediate rewards is
      known as delay discounting. High delay discounting or a bias towards immediate
      gratification impedes self-regulation and is associated with maladaptive eating
      behaviors. Children in general show greater delay discounting than adults. Obese
      children in particular, have greater difficulty delaying gratification for edible
      rewards. Episodic future thinking (EFT) which is mental self-projection to pre
      experience future events reduces delay discounting and reduces energy intake in
      overweight/obese adults. However, these EFT effects have not been examined in
      children. We evaluated the effects of EFT versus control episodic recent thinking
      (ERT) on delay discounting and ad libitum energy intake while thinking about
      episodic cues in 42 overweight/obese 9 to 14year olds. Results showed that EFT
      led to less delay discounting and lowered energy intake, and EFT had the greatest
      effect on reducing energy intake in children with a higher desire to restrict
      food intake. This suggests that EFT may be useful in pediatric obesity treatment
      programs to help children regulate energy intake. 

PMID- 25863229
TI  - Distribution of Hypoxia-Inducible Factor-1alpha and Glucose Transporter-1 in
      Human Tongue Cancers.
AB  - PURPOSE: Oral squamous cell carcinomas have the potential for rapid and unlimited
      growth. Therefore, hypoxic tissue areas are common in these malignant tumors and
      contribute to cancer progression, therapy resistance, and poor outcomes. The aim
      of the present study was to analyze the gene product distribution of hypoxia
      inducible factor-1alpha (HIF-1alpha) and glucose transporter-1 (GLUT-1) in cases
      of tongue squamous cell carcinoma (TSCC) and to identify a preliminary
      correlation between these proteins and clinical staging and Brynes's histologic
      grading system (HGS). MATERIALS AND METHODS: The sample included 57 cases of
      TSCC. Histologic sections of 3 MUm were submitted to the immunoperoxidase method
      and semiquantitative analysis. The association between HIF-1alpha and GLUT-1
      expression in TSCC and the clinical stage and the HGS of Bryne (1998) was
      evaluated using the chi(2) test, with the significance level set at 0.05 (alpha =
      0.05). RESULTS: HIF-1alpha was mainly expressed in the nucleus/cytoplasm of
      neoplastic cells, most specimens exhibited diffuse staining in neoplastic cells
      (84.2%), and focal staining was only observed in perinecrotic areas (15.8%). GLUT
      1 was expressed in the cytoplasm and membrane of malignant cells, and diffuse
      staining was observed in all cases. The intensity of HIF-1alpha expression
      correlated significantly with clinical stage (P = .011) and HGS (P = .002). A
      significant association was observed between the distribution of HIF-1alpha
      expression and metastasis (P = .040). Immunoexpression of GLUT-1 correlated
      significantly with clinical stage (P = .002) and HGS (P = .000). GLUT-1
      expression in the peripheral island was predominant in most low-grade tumors
      (78.6%); in the high-grade cases, the expression prevailed in the location
      center/periphery (55.8%). Comparison of the location of the tumor island in the
      different histologic grades showed a statistically significant difference (P =
      .025). CONCLUSION: The expression of HIF and GLUT proteins within TSCC appears to
      be associated with disease stage, grade, and the presence of metastases.
      Additional studies are needed to evaluate the diagnostic and prognostic uses of
      these proteins in the treatment of TSCC.

PMID- 25863228
TI  - Racial and ethnic differences in contraceptive use among women who desire no
      future children, 2006-2010 National Survey of Family Growth.
AB  - OBJECTIVE: To evaluate racial/ethnic differences in contraceptive use among women
      who do not desire future pregnancy. STUDY DESIGN: We used the 2006-2010 National
      Survey of Family Growth to examine the associations between race/ethnicity and 1)
      use of any contraceptive method at last heterosexual intercourse and 2)
      effectiveness of contraceptive method used among women who stated that they did
      not desire any (more) children. We conducted multivariable logistic regression to
      assess the independent effect of race/ethnicity on these outcomes, adjusting for
      socio-demographic factors, reproductive characteristics, and indicators of
      healthcare access and utilization. RESULTS: The study sample consisted of 2900
      women, aged 15-44 years. The vast majority of women (91.2%) used contraception at
      last sex, although this varied significantly by race/ethnicity (p<.01). In the
      fully adjusted model controlling for demographic and reproductive characteristics
      as well as healthcare access, compared to whites, black women were significantly
      less likely to use any contraception at last sex (OR: 0.43; 95% CI: 0.27-0.73),
      while there was no significant difference for Hispanic women (OR: 0.95; 95% CI:
      0.52-1.72). Among women who used a method at last sex, the type of contraceptive
      method varied significantly by race/ethnicity in bivariate analysis (p<.01),
      although most women (59%) used a highly effective method. In the fully adjusted
      model, racial/ethnic differences were no longer significant. CONCLUSIONS: In this
      nationally representative cohort of women who report that they do not desire
      (more) children, black women were significantly less likely than white women to
      use any contraception at last intercourse; this difference did not appear to be
      due to differential access to health care. IMPLICATIONS: Significant
      racial/ethnic differences exist in contraceptive use among women who have
      completed childbearing, which do not appear to be explained by differential
      socioeconomic status, reproductive characteristics or utilization of healthcare.
      Other factors, including social mobility and locus of reproductive control, that
      may contribute to these variations should be further explored.

PMID- 25863230
TI  - High C-Terminal Cross-Linking Telopeptide Levels Are Associated With a Minimal
      Risk of Osteonecrosis of the Jaws in Patients Taking Oral Bisphosphonates and
      Having Exodontia.
AB  - PURPOSE: The clinical significance of bone turnover marker C-terminal cross
      linking telopeptide (CTX) levels less than 150 pg/mL among recipients of oral
      bisphosphonate (OBP) medications who develop osteonecrosis of the jaws (MRONJ)
      after exodontia is unclear. We searched the published data to determine the
      prevalence of such levels and the association, if any, with development of MRONJ.
      MATERIALS AND METHODS: A systematic review of published studies in the PubMed
      database was undertaken to ascertain the prevalence of preoperative, fasting CTX
      levels less than 150 pg/mL among recipients of OBP scheduled for exodontia and to
      determine whether such levels are associated with the development of
      postoperative MRONJ. The data were aggregated and analyzed to provide the
      sensitivity, specificity, and positive and negative predictive values of the
      association between low CTX levels and the development of MRONJ. RESULTS: Two
      studies were chosen for review. The first, with an enrollment of 21 patients,
      reported that 10 (48%) patients had a preoperative CTX level less than 150 pg/mL
      and that after exodontia, none developed MRONJ. The second study, with an
      enrollment of 950 patients, reported that approximately 282 (30%) had a
      preoperative CTX level less than 150 pg/mL. All the patients with depressed CTX
      levels were offered a "drug holiday"; however, only 101 accepted the offer. Of
      the remaining 181 patients, 4 developed MRONJ. The aggregated study data have
      demonstrated that 30% of patients evidence CTX levels less than 150 pg/mL and
      that the sensitivity and specificity of these levels in association with the
      development of MRONJ was 100% and 80.7%, respectively. The positive predictive
      value was 2.09% and the negative predictive value was 100%. CONCLUSION: The
      published data suggest that approximately one third of patients exposed to OBP
      will evidence depressed CTX levels and that only a very small minority (~2%) will
      develop postexodontia MRONJ. Prudence would suggest that patients scheduled for
      exodontia and receiving OBPs should be informed about the strengths and
      weaknesses of the CTX test and that it should be offered during the consent
      process.

PMID- 25863231
TI  - Sialadenitis Without Sialolithiasis Treated by Sialendoscopy.
AB  - PURPOSE: The aim of the present study was to evaluate the effectiveness of
      interventional sialendoscopy in the management of non-stone obstructive
      sialadenitis. PATIENTS AND METHODS: In the present retrospective study, we
      assessed the treatment outcomes of 51 patients (34 women and 17 men) who had been
      diagnosed with sialadenitis without salivary duct stones. The included patients
      had an obstructive duct condition coupled with recurrent episodes of swelling or
      pain in a major salivary gland. The patients who had a sialolith detected during
      the sialendoscopic procedure or by preoperative imaging were excluded from the
      present study. The outcomes assessment was based on successful removal of the
      obstructive etiology during the endoscopic procedure and the absence of clinical
      symptoms after 6 months. The involved glands included 16 submandibular glands and
      35 parotid glands. RESULTS: The sialendoscopic navigation was successful in 43 of
      51 patients (84%). Of the 43 patients, 37 (86%) were free of symptoms from the
      obstructive gland after the endoscopic procedure. Of the 6 patients who were
      still symptomatic after the procedure, 5 had involvement of the parotid gland.
      Finally, 1 of the original 37 symptom-free patients developed recurrent symptoms
      and denied additional treatment, resulting in 36 of 43 patients (84%) remaining
      asymptomatic 6 months after endoscopic navigation. CONCLUSION: The outcomes of
      the present study suggest that interventional sialendoscopy can provide
      symptomatic improvement in most subjects. Clinicians should consider
      sialendoscopy as a useful and minimally invasive procedure to treat sialadenitis
      without sialolithiasis.

PMID- 25863232
TI  - Combination of imatinib and clotrimazole enhances cell growth inhibition in T47D
      breast cancer cells.
AB  - Imatinib mesylate (IM), a tyrosine kinase inhibitor, is used as targeted cancer
      therapy. However, mono-targeting by IM does not always achieve full tumor
      eradication and thus it is recommended to combine IM with other anticancer
      agents. Clotrimazole (CLT) is an antifungal azole derivative with promising
      anticancer effects due to inhibiting the activity of glycolytic enzymes. The
      present study aimed to evaluate the effect of combining CLT with IM on breast
      cancer cell line in an attempt to establish effective new combination. T47D human
      breast cancer cell line was treated with different concentrations of IM and/or
      CLT for 48 h. IM-CLT interaction was determined by isobologram equation and
      combination index. Cell viability was confirmed by measuring LDH activity. As
      indicators of glycolysis inhibition, the expression of hexokinase-2 (HK-2) and 6
      phosphofructo-1-kinase (PFK-1) plus the activity of intracellular lactate
      dehydrogenase (LDH) and pyruvate kinase (PK) were determined. In addition,
      glucose consumption and adenosine triphosphate (ATP) production were measured.
      Moreover, nitric oxide (NO), vascular endothelial growth factor (VEGF) and
      hypoxia inducible factor-alpha (HIF-alpha) were also determined as they are
      modulators for glycolysis. This study demonstrated that IM or CLT synergistically
      inhibited cell growth in T47D as shown by combination and dose reduction indices.
      The combination of 15 MUM IM and 20 MUM CLT significantly decreased glucose
      consumption, activity of both PK and intracellular LDH, while increased leaked
      LDH, VEGF and NO in the medium compared to each drug alone. Furthermore the
      combination decreased gene expression of HK-2, PFK-1 and ATP content compared to
      the control. In conclusion, the synergistic effect of CLT on IM cytotoxicity in
      T47D cell line maybe mediated through inhibition of glycolysis and increasing
      both NO and VEGF. Further studies are required to confirm the efficiency and
      safety of this combination.

PMID- 25863233
TI  - Expression of receptor activator of nuclear factor-kappaB ligand is related to
      sex differences in collagen-induced arthritis.
AB  - Osteoclasts are responsible for bone destruction in rheumatoid arthritis, and
      women show greater disease activity and functional disability than men. This
      study aimed to examine differences in the pathogenesis of collagen-induced
      arthritis and osteoclastogenesis between female and male mice in vivo and in
      vitro. Female mice exhibited worse disease progression and increased
      osteoclastogenesis, as measured by tartrate-resistant acid phosphatase (TRAP)
      staining than male mice. Significantly higher levels of CD11b(+) cells were
      detected in the bone marrow of female mice than that of male mice. Furthermore,
      the mRNA expression of receptor activator of nuclear factor-kappaB ligand was
      higher in female mice that were immunized with or without collagen II. These
      findings highlighted sex differences in arthritis morbidity and suggested that
      female mice are more likely to develop arthritis than male mice. Further studies
      are needed to investigate the mechanisms of sex differences in collagen-induced
      arthritis. 

PMID- 25863234
TI  - All-trans retinoic acid favors the development and function of regulatory T cells
      from liver transplant patients.
AB  - Graft-versus-host disease (GVHD) is an intractable complication in transplant
      patients. Regulatory T cells (Tregs) have the ability to prevent GVHD and consist
      of two subsets: natural Tregs (nTregs) and induced Tregs (iTregs). In comparison
      to nTregs, iTregs originate in the periphery under certain conditions and show
      improved proliferative and suppressive abilities in an inflammatory milieu. All
      trans retinoic acid (atRA) favors Treg expansion and FoxP3 expression in human
      Tregs. However, whether atRA can affect the function of iTregs from transplant
      patients remains inconclusive. Therefore, we sorted naive T cells from liver
      transplant patients and cultured them in vitro. Further analyses were performed
      to assess the suppressive function of iTregs in vitro and in vivo. atRA favored
      expansion and forkhead box P3 expression in iTregs from transplant patients. In
      comparison to iTregs from healthy donors, iTregs from transplant patients showed
      decent suppressive abilities in vitro and in vivo. Our findings suggest that atRA
      can potentially improve the development and function of iTregs from transplant
      patients. Furthermore, our results provide novel insights into Treg therapy in
      GVHD clinical trials. 

PMID- 25863235
TI  - Anti-inflammatory effects of eugenol on lipopolysaccharide-induced inflammatory
      reaction in acute lung injury via regulating inflammation and redox status.
AB  - Acute lung injury (ALI) represents a clinical syndrome that results from complex
      responses of the lung to a multitude of direct and indirect insults. This study
      aims to evaluate the possible mechanisms responsible for the anti-inflammatory
      effects of eugenol (EUL) on lipopolysaccharide (LPS)-induced inflammatory
      reaction in ALI. ALI was induced in mice by intratracheal instillation of LPS
      (0.5 mg/kg), and EUL (5, and 10 mg/kg) was injected intraperitoneally 1h prior to
      LPS administration. After 6h, bronchoalveolar lavage fluid (BALF) and lung tissue
      were collected. The findings suggest that the protective mechanism of EUL may be
      attributed partly to decreased production of proinflammatory cytokines through
      the regulating inflammation and redox status. The results support that use of EUL
      is beneficial in the treatment of ALI.

PMID- 25863236
TI  - Therapeutic effects of R8, a semi-synthetic analogue of Vasicine, on murine model
      of allergic airway inflammation via STAT6 inhibition.
AB  - This is a follow-up study of our previous work in which we screened a series of
      Vasicine analogues for their anti-inflammatory activity in a preventive OVA
      induced murine model of asthma. The study demonstrated that R8, one of the
      analogues, significantly suppressed the Th2 cytokine production and eosinophil
      recruitment to the airways. In the present study, we have been using two standard
      experimental murine models of asthma, where the mice were treated with R8 either
      during (preventive use) or after (therapeutic use) the development of asthma
      features. In the preventive model, R8 reduced inflammatory cell infiltration to
      the airways, OVA specific IgE and Th2 cytokine production. Also, the R8 treatment
      in the therapeutic model decreased methacholine induced AHR, Th2 cytokine
      release, serum IgE levels, infiltration of inflammatory cells into the airways,
      phosphorylation of STAT6 and expression of GATA3. Moreover, R8 not only reduced
      goblet cell metaplasia in asthmatic mice but also reduced IL-4 induced Muc5AC
      gene expression in human alveolar basal epithelial cells. Further, R8 attenuated
      IL-4 induced differentiation of murine splenocytes into Th2 cells in vitro. So,
      we may deduce that R8 treatment profoundly reduced asthma features by attenuating
      the differentiation of T cells into Th2 cells by interfering with the binding of
      IL-4 to its receptor in turn decreasing the phosphorylation of STAT6 and
      expression of GATA3 in murine model of asthma. These preclinical findings suggest
      a possible therapeutic role of R8 in allergic asthma.

PMID- 25863238
TI  - Predicting brain activation patterns associated with individual lexical concepts
      based on five sensory-motor attributes.
AB  - While major advances have been made in uncovering the neural processes underlying
      perceptual representations, our grasp of how the brain gives rise to conceptual
      knowledge remains relatively poor. Recent work has provided strong evidence that
      concepts rely, at least in part, on the same sensory and motor neural systems
      through which they were acquired, but it is still unclear whether the neural code
      for concept representation uses information about sensory-motor features to
      discriminate between concepts. In the present study, we investigate this question
      by asking whether an encoding model based on five semantic attributes directly
      related to sensory-motor experience - sound, color, visual motion, shape, and
      manipulation - can successfully predict patterns of brain activation elicited by
      individual lexical concepts. We collected ratings on the relevance of these five
      attributes to the meaning of 820 words, and used these ratings as predictors in a
      multiple regression model of the fMRI signal associated with the words in a
      separate group of participants. The five resulting activation maps were then
      combined by linear summation to predict the distributed activation pattern
      elicited by a novel set of 80 test words. The encoding model predicted the
      activation patterns elicited by the test words significantly better than chance.
      As expected, prediction was successful for concrete but not for abstract
      concepts. Comparisons between encoding models based on different combinations of
      attributes indicate that all five attributes contribute to the representation of
      concrete concepts. Consistent with embodied theories of semantics, these results
      show, for the first time, that the distributed activation pattern associated with
      a concept combines information about different sensory-motor attributes according
      to their respective relevance. Future research should investigate how additional
      features of phenomenal experience contribute to the neural representation of
      conceptual knowledge. 

PMID- 25863239
TI  - Ceci n'est pas science.
AB  - Biomedical research is not immune to economic imperatives. But as the realities
      of profit encroach ever closer on what was once regarded as an idealistic and
      selfless endeavor, the author reflects on four trends that are hollowing out the
      research enterprise. 

PMID- 25863237
TI  - Common coding and dynamic interactions between observed, imagined, and
      experienced motor and somatosensory activity.
AB  - Motor imagery and perception - considered generally as forms of motor simulation 
      share overlapping neural representations with motor production. While much
      research has focused on the extent of this "common coding," less attention has
      been paid to how these overlapping representations interact. How do imagined,
      observed, or produced actions influence one another, and how do we maintain
      control over our perception and behavior? In the first part of this review we
      describe interactions between motor production and motor simulation, and explore
      apparent regulatory mechanisms that balance these processes. Next, we consider
      the somatosensory system. Numerous studies now support a "sensory mirror system"
      comprised of neural representations activated by either afferent sensation or
      vicarious sensation. In the second part of this review we summarize evidence for
      shared representations of sensation and sensory simulation (including imagery and
      observed sensation), and suggest that similar interactions and regulation of
      simulation occur in the somatosensory domain as in the motor domain. We suggest
      that both motor and somatosensory simulations are flexibly regulated to support
      simulations congruent with our sensorimotor experience and goals and suppress or
      separate the influence of those that are not. These regulatory mechanisms are
      frequently revealed by cases of brain injury but can also be employed to
      facilitate sensorimotor rehabilitation. 

PMID- 25863240
TI  - Apple or pear: size and shape matter.
AB  - Obesity-related morbidity and mortality are related to fat accumulation and fat
      distribution in humans. Two large-scale meta-analyses recently published in
      Nature by Shungin et al. (2015) and Locke et al. (2015) report novel genetic
      associations for central and overall obesity; these greatly advance our
      understanding of the biology of obesity.

PMID- 25863241
TI  - Hold the salt: vasopressor role for BDNF.
AB  - In a recent publication in Neuron, Choe et al. (2015) demonstrate that brain
      derived neurotrophic factor (BDNF) signaling mediates salt-induced blood pressure
      elevation by increasing the excitability of hypothalamic vasopressin-secreting
      neurons. These findings suggest complex roles for BDNF in adaptive cardiovascular
      responses to physiological challenges and in the pathogenesis of hypertension.

PMID- 25863242
TI  - Exercise controls non-coding RNAs.
AB  - The mechanisms by which exercise regulates physiological cardiac growth and
      protects against maladaptive remodeling of the heart have been long sought after.
      In this issue, Liu et al. (2015) report that microRNAs are important regulators
      of exercise responses in the heart.

PMID- 25863243
TI  - Inflammasome inhibition: putting out the fire.
AB  - NLRP3-inflammasome activates caspase-1 and processes pro-IL-1beta and pro-IL-18
      into the active cytokines. Two recent studies describe specific inhibitors of
      NLRP3 inflammasome that inhibit IL-1beta release and inflammation. The
      specificity and potency of these compounds gives hope that a targeted approach to
      inhibit NLRP3-driven inflammation may be just around the corner. 

PMID- 25863244
TI  - One small step for muscle: a new micropeptide regulates performance.
AB  - Micropeptides represent an emerging class of eukaryotic regulators that are
      easily missed in conventional genome annotation. Anderson et al. (2015) describe
      how a new tissue-specific micropeptide, myoregulin (MLN), interacts with the
      skeletal muscle calcium handling machinery to moderate contractile activity,
      representing a promising drug target for improving muscle performance.

PMID- 25863245
TI  - Uncoupling nuclear receptor LXR and cholesterol metabolism in cancer.
AB  - Liver X receptors (LXRs) are members of the nuclear receptor superfamily of DNA
      binding transcription factors and act as sensors of cholesterol homeostasis.
      Under normal conditions, when intracellular cholesterol concentration increases,
      cells synthesize oxysterols and activate the LXR transcriptional network to drive
      cholesterol efflux and reduce cholesterol influx and synthesis. During normal and
      cancer cell proliferation, there is a net uncoupling between intracellular
      cholesterol increase and LXR activation resulting from the reduced intracellular
      oxysterol concentration. This review dissects the novel mechanisms of a
      previously unrecognized metabolic uncoupling, supporting the activation of the
      LXR axis as a bona fide therapeutic approach in cancer.

PMID- 25863246
TI  - Regulation of obesity-related insulin resistance with gut anti-inflammatory
      agents.
AB  - Obesity has reached epidemic proportions, but little is known about its influence
      on the intestinal immune system. Here we show that the gut immune system is
      altered during high-fat diet (HFD) feeding and is a functional regulator of
      obesity-related insulin resistance (IR) that can be exploited therapeutically.
      Obesity induces a chronic phenotypic pro-inflammatory shift in bowel lamina
      propria immune cell populations. Reduction of the gut immune system, using beta7
      integrin-deficient mice (Beta7(null)), decreases HFD-induced IR. Treatment of
      wild-type HFD C57BL/6 mice with the local gut anti-inflammatory, 5
      aminosalicyclic acid (5-ASA), reverses bowel inflammation and improves metabolic
      parameters. These beneficial effects are dependent on adaptive and gut immunity
      and are associated with reduced gut permeability and endotoxemia, decreased
      visceral adipose tissue inflammation, and improved antigen-specific tolerance to
      luminal antigens. Thus, the mucosal immune system affects multiple pathways
      associated with systemic IR and represents a novel therapeutic target in this
      disease.

PMID- 25863247
TI  - Antigen- and cytokine-driven accumulation of regulatory T cells in visceral
      adipose tissue of lean mice.
AB  - A unique population of Foxp3(+)CD4(+) regulatory T (Treg) cells, with a distinct
      transcriptome and antigen-receptor repertoire, resides in visceral adipose tissue
      (VAT) of lean individuals. These cells regulate local inflammation and both local
      and systemic metabolic indices. Here we focus on expansion of the VAT Treg
      compartment in aging lean mice-assessing these cells' phenotypic conversion from
      conventional CD4(+) T cells, influx from lymphoid organs, and local population
      dynamics. Our findings establish that the VAT Treg compartment is seeded from
      thymocytes generated during the first weeks of life and expands beyond 10 weeks
      of age due to indolent proliferation, of certain clones in particular, coupled
      with enhanced survival. Accumulation of VAT Tregs depends on the antigen(s)
      presented by MHC class-II molecules and soluble mediators, notably
      interleukin(IL)-33. Addressing such factors therapeutically promises novel
      approaches for harnessing Tregs to stem the growing epidemic of obesity and
      consequent metabolic abnormalities.

PMID- 25863248
TI  - miR-222 is necessary for exercise-induced cardiac growth and protects against
      pathological cardiac remodeling.
AB  - Exercise induces physiological cardiac growth and protects the heart against
      pathological remodeling. Recent work suggests exercise also enhances the heart's
      capacity for repair, which could be important for regenerative therapies. While
      microRNAs are important in certain cardiac pathologies, less is known about their
      functional roles in exercise-induced cardiac phenotypes. We profiled cardiac
      microRNA expression in two distinct models of exercise and found microRNA-222
      (miR-222) was upregulated in both. Downstream miR-222 targets modulating
      cardiomyocyte phenotypes were identified, including HIPK1 and HMBOX1. Inhibition
      of miR-222 in vivo completely blocked cardiac and cardiomyocyte growth in
      response to exercise while reducing markers of cardiomyocyte proliferation.
      Importantly, mice with inducible cardiomyocyte miR-222 expression were resistant
      to adverse cardiac remodeling and dysfunction after ischemic injury. These
      studies implicate miR-222 as necessary for exercise-induced cardiomyocyte growth
      and proliferation in the adult mammalian heart and show that it is sufficient to
      protect the heart against adverse remodeling.

PMID- 25863249
TI  - BMPR2 preserves mitochondrial function and DNA during reoxygenation to promote
      endothelial cell survival and reverse pulmonary hypertension.
AB  - Mitochondrial dysfunction, inflammation, and mutant bone morphogenetic protein
      receptor 2 (BMPR2) are associated with pulmonary arterial hypertension (PAH), an
      incurable disease characterized by pulmonary arterial (PA) endothelial cell (EC)
      apoptosis, decreased microvessels, and occlusive vascular remodeling. We
      hypothesized that reduced BMPR2 induces PAEC mitochondrial dysfunction, promoting
      a pro-inflammatory or pro-apoptotic state. Mice with EC deletion of BMPR2 develop
      hypoxia-induced pulmonary hypertension that, in contrast to non-transgenic
      littermates, does not reverse upon reoxygenation and is associated with reduced
      PA microvessels and lung EC p53, PGC1alpha and TFAM, regulators of mitochondrial
      biogenesis, and mitochondrial DNA. Decreasing PAEC BMPR2 by siRNA during
      reoxygenation represses p53, PGC1alpha, NRF2, TFAM, mitochondrial membrane
      potential, and ATP and induces mitochondrial DNA deletion and apoptosis. Reducing
      PAEC BMPR2 in normoxia increases p53, PGC1alpha, TFAM, mitochondrial membrane
      potential, ATP production, and glycolysis, and induces mitochondrial fission and
      a pro-inflammatory state. These features are recapitulated in PAECs from PAH
      patients with mutant BMPR2.

PMID- 25863250
TI  - IGF2BP2/IMP2-Deficient mice resist obesity through enhanced translation of Ucp1
      mRNA and Other mRNAs encoding mitochondrial proteins.
AB  - Although variants in the IGF2BP2/IMP2 gene confer risk for type 2 diabetes, IMP2,
      an RNA binding protein, is not known to regulate metabolism. Imp2(-/-) mice gain
      less lean mass after weaning and have increased lifespan. Imp2(-/-) mice are
      highly resistant to diet-induced obesity and fatty liver and display superior
      glucose tolerance and insulin sensitivity, increased energy expenditure, and
      better defense of core temperature on cold exposure. Imp2(-/-) brown fat and
      Imp2(-/-) brown adipocytes differentiated in vitro contain more UCP1 polypeptide
      than Imp2(+/+) despite similar levels of Ucp1 mRNA; the Imp2(-/-)adipocytes also
      exhibit greater uncoupled oxygen consumption. IMP2 binds the mRNAs encoding Ucp1
      and other mitochondrial components, and most exhibit increased translational
      efficiency in the absence of IMP2. In vitro IMP2 inhibits translation of mRNAs
      bearing the Ucp1 untranslated segments. Thus IMP2 limits longevity and regulates
      nutrient and energy metabolism in the mouse by controlling the translation of its
      client mRNAs.

PMID- 25863251
TI  - GATM polymorphism associated with the risk for statin-induced myopathy does not
      replicate in case-control analysis of 715 dyslipidemic individuals.
AB  - Statin-induced myopathy (SIM) is the most common reason for discontinuation of
      statin therapy. A polymorphism affecting the gene encoding glycine
      amidinotransferase (GATM rs9806699 G > A) was previously associated with reduced
      risk for SIM. Our objective was to replicate the GATM association in a large,
      multicenter SIM case-control study. Mild and severe SIM cases and age- and gender
      matched controls were enrolled. Participants were genotyped, and associations
      were tested (n = 715) using chi-square and logistic regression with consideration
      for SIM severity and exclusion of subjects with potentially confounding
      comedications. The minor allele (A) frequencies of GATM rs9806699 in the controls
      (n = 106), mild SIM (n = 324), and severe SIM (n = 285) cases were 0.26, 0.28,
      and 0.29, respectively (p = 0.447). The unadjusted odds ratio for the A allele
      for any SIM (mild or severe) was 1.14 (0.82-1.61; p = 0.437), which remained
      nonsignificant in all models. Our results do not replicate the association
      between GATM rs9806699 and SIM.

PMID- 25863252
TI  - Dependence of hippocampal function on ERRgamma-regulated mitochondrial
      metabolism.
AB  - Neurons utilize mitochondrial oxidative phosphorylation (OxPhos) to generate
      energy essential for survival, function, and behavioral output. Unlike most cells
      that burn both fat and sugar, neurons only burn sugar. Despite its importance,
      how neurons meet the increased energy demands of complex behaviors such as
      learning and memory is poorly understood. Here we show that the estrogen-related
      receptor gamma (ERRgamma) orchestrates the expression of a distinct neural gene
      network promoting mitochondrial oxidative metabolism that reflects the
      extraordinary neuronal dependence on glucose. ERRgamma(-/-) neurons exhibit
      decreased metabolic capacity. Impairment of long-term potentiation (LTP) in
      ERRgamma(-/-) hippocampal slices can be fully rescued by the mitochondrial OxPhos
      substrate pyruvate, functionally linking the ERRgamma knockout metabolic
      phenotype and memory formation. Consistent with this notion, mice lacking
      neuronal ERRgamma in cerebral cortex and hippocampus exhibit defects in spatial
      learning and memory. These findings implicate neuronal ERRgamma in the metabolic
      adaptations required for memory formation.

PMID- 25863253
TI  - SIRT3 mediates multi-tissue coupling for metabolic fuel switching.
AB  - SIRT3 is a member of the Sirtuin family of NAD(+)-dependent deacylases and plays
      a critical role in metabolic regulation. Organism-wide SIRT3 loss manifests in
      metabolic alterations; however, the coordinating role of SIRT3 among
      metabolically distinct tissues is unknown. Using multi-tissue quantitative
      proteomics comparing fasted wild-type mice to mice lacking SIRT3, innovative
      bioinformatic analysis, and biochemical validation, we provide a comprehensive
      view of mitochondrial acetylation and SIRT3 function. We find SIRT3 regulates the
      acetyl-proteome in core mitochondrial processes common to brain, heart, kidney,
      liver, and skeletal muscle, but differentially regulates metabolic pathways in
      fuel-producing and fuel-utilizing tissues. We propose an additional maintenance
      function for SIRT3 in liver and kidney where SIRT3 expression is elevated to
      reduce the acetate load on mitochondrial proteins. We provide evidence that SIRT3
      impacts ketone body utilization in the brain and reveal a pivotal role for SIRT3
      in the coordination between tissues required for metabolic homeostasis.

PMID- 25863255
TI  - Hippocampal AP5 treatment impairs both spatial working and reference memory in
      radial maze performance in rats.
AB  - The possible involvement of hippocampal N-methyl-d-aspartate (NMDA) receptors in
      spatial reference and working memory was investigated. Rats were first trained in
      a four-baited/four-unbaited version of the eight-arm radial maze task in which
      only predetermined four arms for each rat were baited with a food pellet. After
      rats reached the learning criterion, their performance was tested under the
      treatment of a NMDA antagonist, AP5 (d,l-2-amino-5-phosphonopentanoic acid, 20
      40nmol), or vehicle into the dorsal hippocampus through the bilaterally implanted
      guide cannulae. AP5 produced dose-dependent increments on both reference and
      working memory errors, but did not have any effect on the running speed.
      Additionally, there were significant correlations between the number of trials to
      criterion in acquisition and the number of reference and working memory errors
      induced by AP5 treatment. The results suggest that hippocampal NMDA receptors are
      involved in both spatial reference and working memory. 

PMID- 25863254
TI  - Imagery vividness ratings during exposure treatment for posttraumatic stress
      disorder as a predictor of treatment outcome.
AB  - Within exposure-based trauma treatments for posttraumatic stress disorder (PTSD),
      imagery vividness during imaginal exposure of the traumatic memory is an
      understudied but potentially important predictor of treatment outcome. Further,
      to our knowledge, this relationship has only been studied in women to date, and
      never among individuals with PTSD and substance use disorders which could impact
      ability to produce vivid mental imagery and its impact. The current study
      investigated whether imagery vividness ratings during in-session exposure
      predicted post-treatment PTSD symptom severity in a sample of men and women with
      comorbid PTSD and substance use disorders, and also examined whether gender
      moderated this relationship. A sample of 71 participants who received an exposure
      based trauma treatment were included in the analyses. PTSD symptom severity was
      assessed using both the Clinician Administered PTSD Scale (CAPS) and the Impact
      of Event Scale-Revised (IES-R). Results varied according to method of assessing
      PTSD symptom severity. Higher imagery vividness was associated with better
      treatment outcome when assessed by the CAPS, with vividness in later sessions
      relating more strongly to outcome than vividness in earlier sessions. With the
      IES-R, higher imagery vividness ratings predicted more favorable treatment
      outcome for men, but less favorable treatment outcomes for women. Findings are
      discussed in the context of using imagery vividness to maximize treatment
      outcomes and future research directions involving scientific replication. 

PMID- 25863256
TI  - Urocortin2 prolongs action potential duration and modulates potassium currents in
      guinea pig myocytes and HEK293 cells.
AB  - We previously reported that activation of corticotropin releasing factor receptor
      type 2 by urocortin2 up-regulates both L-type Ca(2+) channels and intracellular
      Ca(2+) concentration in ventricular myocytes and plays an important role in
      cardiac contractility and arrhythmogenesis. This study goal was to further test
      the hypothesis that urocortin2 may modulate action potentials as well as rapidly
      and slowly activating delayed rectifier potassium currents. With whole cell patch
      clamp techniques, action potentials and slowly activating delayed rectifier
      potassium currents were recorded in isolated guinea pig ventricular myocytes,
      respectively. And rapidly activating delayed rectifier potassium currents were
      tested in hERG-HEK293 cells. Urocortin2 produced a time- and concentration
      dependent prolongation of action potential duration. The EC50 values of action
      potential duration and action potential duration at 90% of repolarization were
      14.73 and 24.3nM respectively. The prolongation of action potential duration of
      urocortin2 was almost completely or partly abolished by H-89 (protein kinase A
      inhibitor) or KB-R7943 (Na(+)/Ca(2+) exchange inhibitor) pretreatment
      respectively. And urocortin2 caused reduction of rapidly activating delayed
      rectifier potassium currents in hERG-HEK293 cells. In addition, urocortin2 slowed
      the rate of slowly activating delayed rectifier potassium channel activation, and
      rightward shifted the threshold of slowly activating delayed rectifier potassium
      currents to more positive potentials. Urocortin2 prolonged action potential
      duration via activation of protein kinase A and Na(+)/ Ca(2+) exchange in
      isolated guinea pig ventricular myocytes in a time- and concentration- dependent
      manner. In hERG-HEK293 cells, urocortin2 reduced rapidly activating delayed
      rectifier potassium current density which may contribute to action potential
      duration prolongation. 

PMID- 25863257
TI  - Effect of nebivolol treatment during pregnancy on the genital circulation, fetal
      growth and postnatal development in the Wistar rat.
AB  - The aim of study was to evaluate the effects of nebivolol, a cardioselective beta
      1 adrenergic receptor blocker of the third generation with vasodilatory
      properties, vs. bisoprolol on the genital circulation, uterine vasculature, fetal
      growth and postnatal development in pregnant Wistar rats. Non invasive
      measurements of systolic and diastolic blood pressure (SBP and DBP) and heart
      rate (HR), and invasive measurement of genital blood flow (GBF) were taken in
      pregnant rats, by tail cuff and transonic probe methods respectively, after an
      oral treatment by gastric gavage with nebivolol (8mg/kg/day) or bisoprolol
      (10mg/kg/day) from day 11 to day 18 of pregnancy. Other morphometrical and
      histological measurements were performed on the ovarian and uterine arteries to
      evaluate the effect of nebivolol on the uterine vasculature. Furthermore,
      postnatal mortality and pup growth were recorded. The data demonstrated that
      nebivolol (compared with bisoprolol) induced a significant decrease in SBP, HR
      and GBF while DBP remained unchanged. Moreover, nebivolol increased the diameter
      and the length of ovarian and uterine arteries and the number of uterine artery
      segmental branches. The results also showed that the body weight gain of newborns
      in the nebivolol group was significantly lower vs. bisoprolol and vs. control
      with a higher mortality rate. The nebivolol action is not only limited to its
      favorable hemodynamic effects represented by a decrease in blood pressure, but it
      also produces adverse effects on fetal growth and postnatal development that may
      limit its therapeutic use in females during pregnancy. 

PMID- 25863258
TI  - Direct and indirect cardiovascular actions of cathinone and MDMA in the
      anaesthetized rat.
AB  - The stimulants cathinone (from Khat leaves) and methylenedioxymeth-amphetamine
      (MDMA) produce adrenoceptor mediated tachycardia and vasopressor actions that may
      be the result of direct receptor stimulation, actions on the noradrenaline
      transporter, and/or displacement of noradrenaline from nerve terminals. Effects
      of cathinone or MDMA were compared with those of the indirect sympathomimetic
      tyramine. Male Wistar rats were anaesthetized with pentobarbitone for blood
      pressure and heart rate recording. Some rats were sympathectomised by treatment
      with 6-hydroxydopamine. In the anaesthetised rat, cathinone, MDMA and tyramine
      (all 0.001-1 mg/kg) produced marked tachycardia, tyramine produced marked pressor
      responses and MDMA produced small pressor responses. The tachycardia to cathinone
      and MDMA was almost abolished by propranolol (1mg/kg). Pretreatment with cocaine
      (1mg/kg) did not significantly affect the tachycardia to cathinone or MDMA, but
      reduced the response to tyramine. However, in sympathectomised rats, the
      tachycardia to cathinone or MDMA was markedly attenuated, but the tachycardia to
      tyramine was only partially reduced. Blood pressure effects of tyramine and MDMA
      were also markedly attenuated by sympathectomy. The results demonstrate firstly
      that cocaine may not be the most suitable agent for assessing direct versus
      indirect agonism in cardiovascular studies. Secondly, the use of chemical
      sympathectomy achieved the desired goal of demonstrating that cardiac beta
      adrenoceptor mediated actions of cathinone and MDMA are probably largely
      indirect. 

PMID- 25863259
TI  - Protective effects of dendrosomal curcumin on an animal metastatic breast tumor.
AB  - Curcumin has been shown to inhibit migration and invasion of cancer angiogenesis
      via interacting with key regulatory molecules like NF-kappaB. Rapidly metabolized
      and conjugated in the liver, curcumin has the limited systemic bioavailability.
      Previous results have shown a new light of potential biocompatibility,
      biodegradability, as well as anti-cancer effects of dendrosomal curcumin (DNC) in
      biological systems. The present study aims to deliberate the protective effects
      of DNC on metastatic breast tumor in vitro and in vivo. After the dosing
      procedure, twenty-seven female mice were divided into 40 and 80mg/kg groups of
      DNC, along with a control group to investigate the anti-metastatic effects of DNC
      on mammary tumor-bearing mice. In vitro results showed that the different
      concentrations of DNC reduced the migration and the adhesion of 4T1 cells after
      24h (P<0.05). Under the dosing procedure, DNC was safe at 80mg/kg and lower
      doses. The treated DNC animals had a higher survival rate and lower metastatic
      signs (14%) compared to control (100%) (P<0.05). The metastatic tumors were more
      common in control mice than the treated groups in the lung, the liver and the
      sternum tissues. Animals treated with DNC had smaller tumor volume in comparison
      with control group (P<0.05). Final mean tumor volume reached to approximately
      1.11, 0.31 and 0.27cm(3) in the control, and 40 and 80mg/kg DNC groups,
      respectively (P<0.05). Furthermore, suppression of NF-kappaB expression by DNC
      led to down-regulation of VEGF, COX-2, and MMP-9 expressions in the breast tumor,
      the lung, the brain, the spleen and the liver tissues (P<0.05). These outcomes
      indicate that dendrosomal curcumin has a chemoprotective effect on the breast
      cancer metastasis through suppression of NF-kappaB and its regulated gene
      products. 

PMID- 25863260
TI  - Heparanase stimulates chondrogenesis and is up-regulated in human ectopic
      cartilage: a mechanism possibly involved in hereditary multiple exostoses.
AB  - Hereditary multiple exostoses is a pediatric skeletal disorder characterized by
      benign cartilaginous tumors called exostoses that form next to growing skeletal
      elements. Hereditary multiple exostoses patients carry heterozygous mutations in
      the heparan sulfate (HS)-synthesizing enzymes EXT1 or EXT2, but studies suggest
      that EXT haploinsufficiency and ensuing partial HS deficiency are insufficient
      for exostosis formation. Searching for additional pathways, we analyzed presence
      and distribution of heparanase in human exostoses. Heparanase was readily
      detectable in most chondrocytes, particularly in cell clusters. In control growth
      plates from unaffected persons, however, heparanase was detectable only in
      hypertrophic zone. Treatment of mouse embryo limb mesenchymal micromass cultures
      with exogenous heparanase greatly stimulated chondrogenesis and bone
      morphogenetic protein signaling as revealed by Smad1/5/8 phosphorylation. It also
      stimulated cell migration and proliferation. Interfering with HS function both
      with the chemical antagonist Surfen or treatment with bacterial heparitinase up
      regulated endogenous heparanase gene expression, suggesting a counterintuitive
      feedback mechanism that would result in further HS reduction and increased
      signaling. Thus, we tested a potent heparanase inhibitor (SST0001), which
      strongly inhibited chondrogenesis. Our data clearly indicate that heparanase is
      able to stimulate chondrogenesis, bone morphogenetic protein signaling, cell
      migration, and cell proliferation in chondrogenic cells. These properties may
      allow heparanase to play a role in exostosis genesis and pathogenesis, thus
      making it a conceivable therapeutic target in hereditary multiple exostoses.

PMID- 25863261
TI  - Comparison of four methods of genotyping IL28B polymorphisms in chronic hepatitis
      C patients.
AB  - BACKGROUND: Single nucleotide polymorphisms (SNPs) of the interleukin 28B (IL28B)
      gene are associated with viral clearance and treatment response in hepatitis C
      virus (HCV) infection; however, most of the available SNP genotyping methods are
      expensive. AIMS: This study sought to evaluate the cost effectiveness of four
      methods used to genotype the rs12979860 and rs8099917 SNPs of the IL28B gene.
      METHODS: Tetra-primer amplification-refractory mutation system-polymerase chain
      reaction (ARMS-PCR), restriction fragment length polymorphism (RFLP),
      quantitative (q) PCR and direct sequencing methods were evaluated in terms of
      specificity, cost and run time in 281 blood samples obtained from chronic HCV
      patients. RESULTS: In ARMS-PCR method, the primers designed to target both SNPs
      produced PCR fragments of specific sizes that distinguished the alleles of
      rs12979860 and rs8099917. In RFLP, the band profile allowed the distinction
      between genotypes. The qPCR was the faster and easier to perform. Validation by
      nucleotide sequencing showed 100% agreement among the three methods. The cost for
      a single reaction was lowest for ARMS-PCR, followed in turn by RFLP, qPCR and
      sequencing. CONCLUSIONS: The methodology described for the ARMS-PCR showed the
      most favorable cost-benefit ratio. Moreover, this approach is fast and simple,
      requiring only equipment that is commonly used in molecular diagnosis, which is
      an essential parameter for use in developing countries where laboratories have
      scarce financial resources.

PMID- 25863262
TI  - Implementation of a sampling strategy to detect West Nile virus in oral and
      cloacal samples in live song birds.
AB  - In 1999, West Nile virus (WNV) first appeared in the United States and has
      subsequently infected more than a million people and untold numbers of wildlife.
      Though primarily an avian virus, WNV can also infect humans and horses. The
      current status of WNV and its effects on wildlife in Pennsylvania (PA) is
      sparsely monitored through sporadic testing of dead birds. In order to acquire a
      more comprehensive understanding of the status of WNV in wild birds, a study was
      designed and implemented to sample populations of migratory and local birds at
      Powdermill Nature Reserve near Rector, PA. Resident and migratory bird species
      totaling 276 individuals were sampled cloacally and orally to compare the
      effectiveness of sampling methods. The presence of WNV was tested for using RT
      PCR. Two positive samples were found, one from a migrating Tennessee warbler and
      another from an American robin. The low infection rates indicate that WNV may not
      be a critical conservation concern in the Westmoreland County region of PA. There
      was also agreement between oral and cloacal swabs, which provides support for
      both methods. This study describes a surveillance method that is easily
      incorporated into any banding operation and which determines the risks of WNV to
      various bird populations. 

PMID- 25863263
TI  - You did not mean it: Perceived good intentions alleviate sense of unfairness.
AB  - Previous research has reported that feedback-related negativity (FRN) may
      represent the degree of perceived unfairness in the ultimatum game (UG). However,
      few studies have incorporated intention-related consideration in examining the
      neural correlates of fairness perception. To address this issue, the present
      study introduced an intentional UG paradigm to disentangle the effect of
      perceived intention from fairness concerns, using an event-related potential
      (ERP) analysis. Consistent with the hypothesis, the behavioral results indicated
      that good intention could markedly reduce rejection rates, and this intention
      effect was modulated by the degree of fairness, which was more prominent under
      unfair scenarios. Further electrophysiological results showed that, for the
      unfair division schemes, FRN and P300 amplitudes were significantly different
      between offers proposed with good intention and those with bad intention, while
      such discrepancies were not observed for the fair condition. In summary,
      converging results demonstrated that perceived intention can modulate the effect
      of fairness in social decision-making. 

PMID- 25863264
TI  - Retinal damage induced by commercial light emitting diodes (LEDs).
AB  - Spectra of "white LEDs" are characterized by an intense emission in the blue
      region of the visible spectrum, absent in daylight spectra. This blue component
      and the high intensity of emission are the main sources of concern about the
      health risks of LEDs with respect to their toxicity to the eye and the retina.
      The aim of our study was to elucidate the role of blue light from LEDs in retinal
      damage. Commercially available white LEDs and four different blue LEDs (507, 473,
      467, and 449nm) were used for exposure experiments on Wistar rats.
      Immunohistochemical stain, transmission electron microscopy, and Western blot
      were used to exam the retinas. We evaluated LED-induced retinal cell damage by
      studying oxidative stress, stress response pathways, and the identification of
      cell death pathways. LED light caused a state of suffering of the retina with
      oxidative damage and retinal injury. We observed a loss of photoreceptors and the
      activation of caspase-independent apoptosis, necroptosis, and necrosis. A
      wavelength dependence of the effects was observed. Phototoxicity of LEDs on the
      retina is characterized by a strong damage of photoreceptors and by the induction
      of necrosis. 

PMID- 25863265
TI  - Regulating malonyl-CoA metabolism via synthetic antisense RNAs for enhanced
      biosynthesis of natural products.
AB  - Malonyl-CoA is the building block for fatty acid biosynthesis and also a
      precursor to various pharmaceutically and industrially valuable molecules, such
      as polyketides and biopolymers. However, intracellular malonyl-CoA is usually
      maintained at low levels, which poses great challenges to efficient microbial
      production of malonyl-CoA derived molecules. Inactivation of the malonyl-CoA
      consumption pathway to increase its intracellular availability is not applicable,
      since it is usually lethal to microorganisms. In this work, we employ synthetic
      antisense RNAs (asRNAs) to conditionally down-regulate fatty acid biosynthesis
      and achieve malonyl-CoA enrichment in Escherichia coli. The optimized asRNA
      constructs with a loop-stem structure exhibit high interference efficiency up to
      80%, leading to a 4.5-fold increase in intracellular malonyl-CoA concentration
      when fabD gene expression is inhibited. Strikingly, this strategy allows the
      improved production of natural products 4-hydroxycoumarin, resveratrol, and
      naringenin by 2.53-, 1.70-, and 1.53-fold in E. coli, respectively. In addition,
      down-regulation of other fab genes including fabH, fabB, and fabF also leads to
      remarkable increases in 4-hydroxycoumarin production. This study demonstrates a
      novel strategy to enhance intracellular malonyl-CoA and indicates the
      effectiveness of asRNA as a powerful tool for use in metabolic engineering. 

PMID- 25863266
TI  - A spatially distributed computational model of brain cellular metabolism.
AB  - This paper develops a three-dimensional spatially distributed model of brain
      cellular metabolism and investigates how the locus of the synaptic activity in
      reference to the capillaries and diffusion affects the behavior of the model, a
      type of analysis which is impossible to carry out in spatially lumped models,
      which are shown to be consistent spatially averaged approximations of the
      distributed model. To avoid a geometrically detailed modeling of the complex
      structure of the tissue consisting of different cell types and the extracellular
      space, the distributed model is based on a novel multi-domain formulation of
      reaction-diffusion equations, accounting also for separate mitochondria. The
      model reduction relating the spatially distributed model and lower dimensional
      reduced models, including the well-mixed spatially lumped compartment model, is
      carefully explained. We illustrate the effects of losing the spatial resolution
      with a computed example which is based on a reduced one-dimensional distributed
      radial model, and look into how the model behaves when the locus of the synaptic
      activity in reference to the capillaries is changed. By averaging the fluxes and
      concentrations in the distributed radial model to correspond to quantities in a
      lumped model, and further by estimating the parameters in the lumped, we conclude
      that varying the locus of the synaptic activity in reference to the capillaries
      alters significantly the lumped model parameters. This observation seems to be
      consequential for parameter estimation procedures from data when the spatial
      resolution is insufficient to determine the locus of the activity, indicating
      that the model uncertainty is an inherent feature of lumped models. 

PMID- 25863267
TI  - A strategy focused on MAPT, APP, NCSTN and BACE1 to build blood classifiers for
      Alzheimer's disease.
AB  - BACKGROUND: Although Alzheimer's disease (AD) is a brain disorder, a number of
      peripheral alterations have been found in these patients, including differences
      in leukocyte gene expression; however, the key genes involved in plaque and
      tangle formation have shown a relatively small potential as diagnostic markers.
      We focused on MAPT, APP, NCSTN and BACE1 as the basis to build and compare blood
      classifiers for AD. METHODS: We used a combined model to build disease
      classifiers, using measures of blood pressure and serum glucose, cholesterol and
      triglyceride levels as well as RT-PCR expression levels of APP, NCSTN and BACE1
      in peripheral blood mononuclear cells (PBMCs) from an independent cohort of 36
      individuals of cognitively-normal controls, AD and other neuropathologies. Also,
      a set of genes was carefully selected by molecular interactions with MAPT, APP,
      NCSTN and BACE1 to test an expression-based classifier in a public microarray
      dataset of 40 samples (AD and controls). A series of discriminant analyses and
      classification and regression trees (C&RTs) were used to perform classification
      tasks. RESULTS: Using C&RTs, the combined model showed potential to
      differentially diagnose AD with up to 94.4% accuracy and 100% specificity for our
      independent sample. Furthermore, a subset of 16 genes showed the best diagnostic
      potential using a minimum number of expression variables, correctly classifying
      up to 100% of samples in the public dataset. CONCLUSIONS: Our unique method of
      variable selection proves that even elements showing no significant differences
      between controls and AD, but that have somehow been linked to AD or AD-related
      elements, still hold a potential to be used in its diagnosis. Sample size and
      inherent methodological limitations of this study need to be kept in mind. Our
      classifiers require careful further testing in larger cohorts. Nonetheless, we
      believe these results provide evidence for the utility of our innovative method,
      which contributes a different approach to generate promising diagnostic tools for
      neuropsychiatric disorders.

PMID- 25863268
TI  - Dynamics in atomic signaling games.
AB  - We study an atomic signaling game under stochastic evolutionary dynamics. There
      are a finite number of players who repeatedly update from a finite number of
      available languages/signaling strategies. Players imitate the most fit agents
      with high probability or mutate with low probability. We analyze the long-run
      distribution of states and show that, for sufficiently small mutation
      probability, its support is limited to efficient communication systems. We find
      that this behavior is insensitive to the particular choice of evolutionary
      dynamic, a property that is due to the game having a potential structure with a
      potential function corresponding to average fitness. Consequently, the model
      supports conclusions similar to those found in the literature on language
      competition. That is, we show that efficient languages eventually predominate the
      society while reproducing the empirical phenomenon of linguistic drift. The
      emergence of efficiency in the atomic case can be contrasted with results for non
      atomic signaling games that establish the non-negligible possibility of
      convergence, under replicator dynamics, to states of unbounded efficiency loss. 

PMID- 25863269
TI  - Towards an integration of mathematical models, theories and observations
      concerning autoimmune diseases.

PMID- 25863270
TI  - Fast and slow interactions of n-alkanols with human 5-HT3A receptors:
      Implications for anesthetic mechanisms.
AB  - This is part of a continuing patch-clamp study exploring molecular actions of
      anesthetics and systematically varied related substances on 5-HT3A receptors as
      prototypes of ligand-gated ion channels. Specifically, n-alkanols, related to but
      simpler in structure than propofol, were studied to explore the complex actions
      of this leading intravenous anesthetic. Outside-out patches excised from HEK 293
      cells heterologously expressing human 5-HT3A receptors were superfused with even
      numbered n-alkanols (ethanol through n-tetradecanol) of different concentrations.
      Fast solution exchange for varying durations allowed separation of drug actions
      by their kinetics. Compared with propofol the electrophysiological responses to n
      alkanols were not much simpler. n-Alkanols produced fast and slow inhibition or
      potentiation of current amplitudes, and acceleration of current rise and decay
      time constants, depending on exposure time, concentration, and chain-length of
      the drug. Inhibition dominated, characterized by fast and slow processes with
      time constants separated by two orders of magnitude which were similar for
      different n-alkanols and for propofol. Absolute interaction energies for ethanol
      to n-dodecanol (relative to xenon) ranged from -10.8 to -37.3kJmol(-1). No two n
      alkanols act completely alike. Potency increases with chain length (until cutoff)
      mainly because of methylene groups interacting with protein sites rather than
      because of their tendency to escape from the aqueous phase. Similar wash-in time
      constants for n-alkanols and propofol suggest similar mechanisms, dominated by
      the kinetics of conformational state changes rather than by binding reactions. 

PMID- 25863271
TI  - Gonadal hormones do not alter the development of antinociceptive tolerance to
      delta-9-tetrahydrocannabinol in adult rats.
AB  - The purpose of this study was to determine whether sex differences in the
      development of antinociceptive tolerance to delta-9-tetrahydrocannabinol (THC)
      are due to activational effects of gonadal hormones. Rats were sham
      gonadectomized (sham-GDX) or gonadectomized (GDX). GDX females received no
      hormone replacement (GDX+0), estradiol (GDX+E2), progesterone (GDX+P4), or both
      (GDX+E2/P4). GDX male rats received no hormone (GDX+0) or testosterone (GDX+T).
      Two weeks later, antinociceptive potency of THC was determined (pre-chronic test)
      on the warm water tail withdrawal and paw pressure assays. Vehicle or a sex
      specific THC dose (females, 5.7mg/kg, males, 9.9mg/kg) was administered twice
      daily for 9days, then the THC dose-effect curves were re-determined (post-chronic
      test). On the pre-chronic test (both assays), THC was more potent in sham-GDX
      females than males, and gonadectomy did not alter this sex difference. In GDX
      females, P4 significantly decreased THC's antinociceptive potency, whereas E2 had
      no effect. In GDX males, T did not alter THC's antinociceptive potency. After
      chronic THC treatment, THC's antinociceptive potency was decreased more in sham
      GDX females than males, on the tail withdrawal test; this sex difference in
      tolerance was not altered in GDX or hormone-treated groups. These results suggest
      that greater antinociceptive tolerance in females, which occurred despite females
      receiving 40% less THC than males, is not due to activational effects of gonadal
      hormones. 

PMID- 25863272
TI  - Poly (ADP-ribose) polymerase-1 inhibitor, 3-aminobenzamide pretreatment
      ameliorates lipopolysaccharide-induced neurobehavioral and neurochemical
      anomalies in mice.
AB  - Poly (ADP-ribose) polymerase-1 (PARP-1) functions at the center of cellular
      stress and sways the immune system at several key points, thus modulates
      inflammatory diseases. The antiinflammatory properties of PARP-1 inhibitors have
      been demonstrated ameliorating effect in various neuroinflammatory disorders. It
      has been reported that there is a close relationship between the inflammatory
      processes and major depressive disorder. In the present study, we have elucidated
      the role of oxidative-nitrosative stress-PARP-1 pathway in lipopolysaccharide
      (LPS)-induced neurobehavioral and neurochemical alterations in mice. 3
      Aminobenzamide (10 and 30mg/kg) and imipramine (10 and 30mg/kg) were administered
      once daily for 14days. Mice were challenged with LPS (1mg/kg, i.p.) 30min after
      drug administration on the 14th day. The mRNA expression level of PARP-1 (12h
      after LPS injection) in the hippocampus was measured through quantitative real
      time PCR. All the behavioral and biochemical parameters were assessed at 24h
      after LPS injection. The expression level of PARP-1mRNA was found significantly
      up-regulated in the hippocampus at 12h after LPS administration. Results showed
      that the LPS-challenged mice exhibited an increase in immobility time seen in
      forced swimming test and tail suspension test. LPS increased the levels of
      proinflammatory cytokines and oxido-nitrosative stress parameters in the
      hippocampus. However, pretreatment with 3-aminobenzamide (30mg/kg) significantly
      reversed the LPS-induced alterations in behavioral parameters, proinflammatory
      cytokines, oxidative-nitrosative stress and PARP-1 mRNA levels. Imipramine failed
      to prevent the up-regulation of PARP-1 induced by LPS administration. Our results
      emphasized that oxidative-nitrosative stress-PARP-1 cascade can play a key role
      in LPS-induced neurobehavioral and neurochemical anomalies. 

PMID- 25863273
TI  - Multifunctional hollow gold nanoparticles designed for triple combination therapy
      and CT imaging.
AB  - Hollow gold nanoparticles (HGNP) are a novel class of hybrid metal nanoparticles
      whose unique optical and morphological properties have spawned new applications
      including more effective cancer therapy. The shell thickness of HGNPs can tune
      the surface plasmon resonance to the near infrared light, resulting in
      photothermal ablation of tumors with optimal light penetration in tissue. The
      hollow cavity within a HGNP is able to accommodate a high payload of
      chemotherapeutic agents. They have also been used for enhancing
      radiosensitization in tumors during radiotherapy due to the high X-ray absorption
      capability of gold particles. However, no report has yet been published that
      utilize HGNPs for the triple combination therapy and CT imaging. In this study,
      we synthesized HGNPs which exhibit better response to radiation for therapy and
      imaging and demonstrated the effects of combined chemotherapy, thermal and
      radiotherapy. This combination strategy presented delayed tumor growth by 4.3
      fold and reduced tumor's weight by 6.8-fold compared to control tumors. In
      addition, we demonstrated the feasibility of HGNP as a CT imaging agent. It is
      expected that translating these capabilities to human cancer patients could
      dramatically increase the antitumor effect and potentially overcome resistance to
      chemotherapeutic agents and radiation. 

PMID- 25863274
TI  - Sesamol attenuates genotoxicity in bone marrow cells of whole-body gamma
      irradiated mice.
AB  - Ionising radiation causes free radical-mediated damage in cellular DNA. This
      damage is manifested as chromosomal aberrations and micronuclei (MN) in
      proliferating cells. Sesamol, present in sesame seeds, has the potential to
      scavenge free radicals; therefore, it can reduce radiation-induced cytogenetic
      damage in cells. The aim of this study was to investigate the radioprotective
      potential of sesamol in bone marrow cells of mice and related haematopoietic
      system against radiation-induced genotoxicity. A comparative study with melatonin
      was designed for assessing the radioprotective potential of sesamol. C57BL/6 mice
      were administered intraperitoneally with either sesamol or melatonin (10 and
      20mg/kg body weight) 30 min prior to 2-Gy whole-body irradiation (WBI) and
      sacrificed after 24h. Total chromosomal aberrations (TCA), MN and cell cycle
      analyses were performed using bone marrow cells. The comet assay was performed on
      bone marrow cells, splenocytes and lymphocytes. Blood was drawn to study
      haematological parameters. Prophylactic doses of sesamol (10 and 20mg/kg) in
      irradiated mice reduced TCA and micronucleated polychromatic erythrocyte
      frequency in bone marrow cells by 57% and 50%, respectively, in comparison with
      radiation-only groups. Sesamol-reduced radiation-induced apoptosis and
      facilitated cell proliferation. In the comet assay, sesamol (20mg/kg) treatment
      reduced radiation-induced comets (% DNA in tail) compared with radiation only (P
      < 0.05). Sesamol also increased granulocyte populations in peripheral blood
      similar to melatonin. Overall, the radioprotective efficacy of sesamol was found
      to be similar to that of melatonin. Sesamol treatment also showed recovery of
      relative spleen weight at 24h of WBI. The results strongly suggest the
      radioprotective efficacy of sesamol in the haematopoietic system of mice.

PMID- 25863275
TI  - A reappraisal of the ileo-rectal anastomosis in ulcerative colitis.
AB  - Colectomy is still frequently required in the care of ulcerative colitis. The
      most common indications are either non-responding colitis in the emergency
      setting, chronic active disease, steroid-dependent disease or neoplastic change
      like dysplasia or cancer. The use of the ileal pouch anal anastomosis has
      internationally been the gold standard, substituting the rectum with a pouch.
      Recently the use of the ileorectal anastomosis has increased in frequency as
      reconstructive method after subtotal colectomy. Data from centres using
      ileorectal anastomosis have shown the method to be safe, with functionality and
      risk of failure comparable to the ileal pouch anal anastomosis. The methods have
      different advantages as well as disadvantages, depending on a number of patient
      factors and where in life the patient is at time of reconstruction. The
      ileorectal anastomosis could, together with the Kock continent ileostomy, in
      selected cases be a complement to the ileal pouch anal anastomosis in ulcerative
      colitis and should be discussed with the patient before deciding on
      reconstructive method. 

PMID- 25863276
TI  - Addition of an immunomodulator as a rescue therapy for loss of response to
      adalimumab dose escalation in patients with Crohn's disease.

PMID- 25863277
TI  - Immune system participates in brain regeneration and restoration of reproduction
      in the earthworm Dendrobaena veneta.
AB  - Earthworm decerebration causes temporary inhibition of reproduction which is
      mediated by certain brain-derived neurohormones; thus, cocoon production is an
      apposite supravital marker of neurosecretory center functional recovery during
      brain regeneration. The core aim of the present study was to investigate aspects
      of the interactions of nervous and immune systems during brain regeneration in
      adult Dendrobaena veneta (Annelida; Oligochaeta). Surgical brain extirpation was
      combined, either with (i) maintenance of immune-competent coelomic cells
      (coelomocytes) achieved by surgery on prilocaine-anesthetized worms or (ii) prior
      extrusion of fluid-suspended coelomocytes by electrostimulation. Both brain
      renewal and cocoon output recovery were significantly faster in earthworms with
      relatively undisturbed coelomocyte counts compared with individuals where
      coelomocyte counts had been experimentally depleted. These observations provide
      empirical evidence that coelomocytes and/or coelomocyte-derived factors (e.g.
      riboflavin) participate in brain regeneration and, by implication, that there is
      close functional synergy between earthworm neural and immune systems. 

PMID- 25863278
TI  - The role of ontologies in biological and biomedical research: a functional
      perspective.
AB  - Ontologies are widely used in biological and biomedical research. Their success
      lies in their combination of four main features present in almost all ontologies:
      provision of standard identifiers for classes and relations that represent the
      phenomena within a domain; provision of a vocabulary for a domain; provision of
      metadata that describes the intended meaning of the classes and relations in
      ontologies; and the provision of machine-readable axioms and definitions that
      enable computational access to some aspects of the meaning of classes and
      relations. While each of these features enables applications that facilitate data
      integration, data access and analysis, a great potential lies in the possibility
      of combining these four features to support integrative analysis and
      interpretation of multimodal data. Here, we provide a functional perspective on
      ontologies in biology and biomedicine, focusing on what ontologies can do and
      describing how they can be used in support of integrative research. We also
      outline perspectives for using ontologies in data-driven science, in particular
      their application in structured data mining and machine learning applications. 

PMID- 25863279
TI  - Potential of the cannabinoid CB(2) receptor as a pharmacological target against
      inflammation in Parkinson's disease.
AB  - Inflammation is an important pathogenic factor in Parkinson's disease (PD), so
      that it can contribute to kill dopaminergic neurons of the substantia nigra and
      to enhance the dopaminergic denervation of the striatum. The cannabinoid type-2
      (CB2) receptor has been investigated as a potential anti-inflammatory and
      neuroprotective target in different neurodegenerative disorders, but still
      limited evidence has been collected in PD. Here, we show for the first time that
      CB2 receptors are elevated in microglial cells recruited and activated at
      lesioned sites in the substantia nigra of PD patients compared to control
      subjects. Parkinsonian inflammation can be reproduced experimentally in rodents
      by intrastriatal injections of lipopolysaccharide (LPS) which, through an intense
      activation of glial elements and peripheral infiltration, provokes a rapid
      deterioration of the striatum that may extend to the substantia nigra too. Using
      this experimental model, we recently described a much more intense deterioration
      of tyrosine hydroxylase (TH)-containing nigral neurons in CB2 receptor-deficient
      mice compared to wild-type animals, supporting a potential neuroprotective role
      for this receptor. In the present study, we further explored this issue. First,
      we found elevated levels of the CB2 receptor measured by qRT-PCR in the striatum
      and substantia nigra of LPS-lesioned mice, as well as an increase in the
      immunostaining for this receptor in the LPS-lesioned striatum. Second, we found a
      significant increase in CD68 immunostaining, which serve to identify activated
      microglia and also infiltrated peripheral macrophages, in these brain structures
      in response to LPS insult, which was much more intense in CB2 receptor-deficient
      mice in the case of the substantia nigra. Next, we observed that the activation
      of CB2 receptors with a selective agonist (HU-308) reversed LPS-induced elevation
      of CD68 immunostaining in the striatum and the parallel reduction in TH
      immunostaining. Lastly, we found that LPS elevated the gene expression of
      different pro-inflammatory mediators in both the striatum and the substantia
      nigra, whereas the selective activation of CB2 receptors reduced a part of these
      mediators, e.g. inducible nitric oxide synthase, although exclusively in the
      striatum. In conclusion, we have provided the first evidence on the up-regulation
      of CB2 receptors in glial elements in postmortem tissues of PD patients, which
      has been confirmed in an inflammatory model of this disease. In addition, we have
      provided evidence on the benefits derived from their activation in relation with
      the activation of microglial cells, the infiltration of macrophages and also
      certain capability of these cells to generate proinflammatory factors. 

PMID- 25863280
TI  - Health changes of refugees from Afghanistan, Iran and Somalia: the role of
      residence status and experienced living difficulties in the resettlement process.
AB  - INTRODUCTION: Worldwide, refugees show a poorer mental and physical health than
      the populations among which they resettle. Little is known about the factors
      influencing health after resettlement. We examined the development of mental and
      physical health of refugees. As experienced living difficulties might decrease
      with obtaining a residence permit, we expected this to play a central role in
      health improvement after resettlement. METHODS: A two-wave study conducted in the
      Netherlands among a cohort of 172 recent (n = 68) and longstanding (n = 104)
      permit holders from Afghanistan, Iran and Somalia between 2003 and 2011.
      Multivariate mediation analyses were conducted for the effect of changes in
      living difficulties on the association between change in status and changes in
      health. Health outcomes were self-reported general health, number of chronic
      conditions, PTSD and anxiety/depression. RESULTS: Recent permit holders had
      larger decreases in PTSD score (-0.402, CI -0.612; -0.192) and anxiety/depression
      score (-0.298, CI -0.464; -0.132), and larger improvements in self-rated general
      health between T1 and T2 (0.566, CI 0.183; 0.949) than longstanding permit
      holders. This association was not significant for changes in number of chronic
      conditions. Mediation analyses showed that the effect of getting a residence
      permit on health improvements transited through an improvement in living
      conditions, in particular employment and the presence of family/social support.
      CONCLUSION: These results suggest that change in residence permit is beneficial
      for health mainly because of the change in living difficulties. These results add
      up to the evidence on the role of social circumstances for refugees upon
      resettlement, and point at labour participation and social support as key
      mechanisms for health improvements.

PMID- 25863281
TI  - Chronic disease prevalence in women and air pollution--A 30-year longitudinal
      cohort study.
AB  - BACKGROUND: Air pollution, such as fine particulate matter (PM2.5), can increase
      risk of adverse health events among people with heart disease, diabetes, asthma
      and chronic obstructive pulmonary disease (COPD) by aggravating these conditions.
      Identifying the influence of PM2.5 on prevalence of these conditions may help
      target interventions to reduce disease morbidity among high-risk populations.
      OBJECTIVES: The objective of this study is to measure the association of exposure
      of PM2.5 with prevalence risk of various chronic diseases among a longitudinal
      cohort of women. METHODS: Women from Ontario who enrolled in the Canadian
      National Breast Screening Study (CNBSS) from 1980 to 1985 (n = 29,549) were
      linked to provincial health administrative data from April 1, 1992 to March 31,
      2013 to determine the prevalence of major chronic disease and conditions (heart
      disease, diabetes, asthma, COPD, acute myocardial infarction, angina, stroke and
      cancers). Exposure to PM2.5 was measured using satellite data collected from
      January 1, 1998 to December 31, 2006 and assigned to resident postal-code at time
      of entry into study. Poisson regression models were used to describe the
      relationship between exposure to ambient PM2.5 and chronic disease prevalence.
      Prevalence rate ratios (PRs) were estimated while adjusting for potential
      confounders: baseline age, smoking, BMI, marital status, education and
      occupation. Separate models were run for each chronic disease and condition.
      RESULTS: Congestive heart failure (PR = 1.31, 95% CI: 1.13, 1.51), diabetes (PR =
      1.28, 95% CI: 1.16, 1.41), ischemic heart disease (PR = 1.22, 95% CI: 1.14,
      1.30), and stroke (PR = 1.21, 95% CI: 1.09, 1.35) showed over a 20% increase in
      PRs per 10 MUg/m(3) increase in PM2.5 after adjusting for risk factors. Risks
      were elevated in smokers and those with BMI greater than 30. CONCLUSIONS: This
      study estimated significant elevated prevalent rate ratios per unit increase in
      PM2.5 in nine of the ten chronic diseases studied.

PMID- 25863282
TI  - Targeted omics analyses, and metabolic enzyme activity assays demonstrate
      maintenance of key mucociliary characteristics in long term cultures of
      reconstituted human airway epithelia.
AB  - 3D reconstituted respiratory epithelia have emerged as better in vitro models for
      toxicological testing compared to cell lines due to the conservation of key
      morphological features and functions. MucilAirTM is a commercially available
      human airway epithelia system that can potentially maintain functional attributes
      for up to a year, however, detailed mucociliary characteristics and xenobiotic
      metabolism relevant to inhaled pro-toxicant bioactivation is lacking. Here, we
      assessed in MucilAirTM some key biomarkers that are characteristic of the
      respiratory epithelia including morphology, function and xenobiotics metabolism.
      The end points that were measured included targeted proteomics using a panel of
      243 airway surface liquid (ASL) proteins, cilia beat frequency (CBF), a qRT-PCR
      screen of xenobiotic metabolizing enzymes, and CYP2A6/13, CYP1A1/1B1 activity.
      Comparison of ASL proteomics with human sputum identified key proteins common to
      both matrices, but present at different levels. Xenobiotic metabolism gene
      profiling demonstrated strong similarities with the normal human lung and did not
      reveal any consistent changes when assessed over a 6 month period. Inducibility
      and activity of CYP1A1/1B1 and activity of CYP2A6/2A13 were present at one month
      in culture and maintained in one tested MucilAirTM donor for several months. In
      conclusion, MucilAirTM presented important morphological and metabolic
      characteristics of a mucociliary epithelium in short and long term culture.
      MucilAirTM is therefore a potentially useful model to test repeated sub-cytotoxic
      doses of toxicants.

PMID- 25863283
TI  - Exogenous sucrose supply changes sugar metabolism and reduces photosynthesis of
      sugarcane through the down-regulation of Rubisco abundance and activity.
AB  - Photosynthetic modulation by sugars has been known for many years, but the
      biochemical and molecular comprehension of this process is lacking. We studied
      how the exogenous sucrose supplied to leaves could affect sugar metabolism in
      leaf, sheath and stalk and inhibit photosynthesis in four-month old sugarcane
      plants. Exogenous sucrose 50mM sprayed on attached leaves strongly impaired the
      net CO2 assimilation (PN) and decreased the instantaneous carboxylation
      efficiency (PN/Ci), suggesting that the impairment in photosynthesis was caused
      by biochemical restrictions. The photosystem II activity was also affected by
      excess sucrose as indicated by the reduction in the apparent electron transport
      rate, effective quantum yield and increase in non-photochemical quenching. In
      leaf segments, sucrose accumulation was related to increases in the activities of
      soluble acid and neutral invertases, sucrose synthase and sucrose phosphate
      synthase, whereas the contents of fructose increased and glucose slightly
      decreased. Changes in the activities of sucrose hydrolyzing and synthesizing
      enzymes in leaf, sheath and stalk and sugar profile in intact plants were not
      enough to identify which sugar(s) or enzyme(s) were directly involved in
      photosynthesis modulation. However, exogenous sucrose was able to trigger down
      regulation in the Rubisco abundance, activation state and enzymatic activity.
      Despite the fact that PN/Ci had been notably decreased by sucrose, in vitro
      activity and abundance of PEPCase did not change, suggesting an in vivo
      modulation of this enzyme. The data reveal that sucrose and/or other derivative
      sugars in leaves inhibited sugarcane photosynthesis by down-regulation of Rubisco
      synthesis and activity. Our data also suggest that sugar modulation was not
      exerted by a feedback mechanism induced by the accumulation of sugars in immature
      sugarcane stalk. 

PMID- 25863284
TI  - mGlu5-GABAB interplay in animal models of positive, negative and cognitive
      symptoms of schizophrenia.
AB  - Diverse preclinical studies exploiting the modulation of the GABAergic and/or
      glutamatergic system in brain via metabotropic receptors suggest their potential
      therapeutic utility. GS39783 and CDPPB, positive allosteric modulators of GABAB
      and mGlu5 receptors, were previously shown to reverse behavioral phenotypes in
      animal models to mimic selected (predominantly positive) symptoms of
      schizophrenia. In the present study we investigated the activity of selected
      GABAB (GS39783 and CGP7930) and mGlu5 (CDPPB) positive allosteric modulators. We
      focused mainly on the aspects of their efficacy in the models of negative and
      cognitive symptoms of schizophrenia. We used modified swim test, social
      interactions (models of negative symptoms) and novel object recognition (model of
      cognitive disturbances). The activity of the compounds was also tested in
      haloperidol-induced catalepsy test. The mutual interaction between GABAB/mGlu5
      ligands was investigated as well. In the second part of the study, DHPG-induced
      PI hydrolysis in the presence of GABAB receptor antagonist (SKF97541), and
      SKF97541-induced inhibition of cAMP formation in the presence of DHPG, was
      performed. Both mGlu5 and GABAB receptor modulators effectively reversed MK-801
      induced deficits in behavioral models of schizophrenia. Moreover, the concomitant
      administration of sub-effective doses of CDPPB and GS39783 induced a clear
      antipsychotic-like effect in all the procedures used, except DOI-induced head
      twitches. The concomitant administration of group I mGlu and GABAB agonists did
      not displayed any synergistic effects in vitro. Summing up, an activation of both
      types of receptor may be a promising mechanism for the development of novel
      antipsychotic drugs, efficacious toward positive, negative and cognitive
      symptoms. 

PMID- 25863285
TI  - Intermolecular recognition of the non-coding RNA 7SK and HEXIM protein in
      perspective.
AB  - A 7SKsnRNP complex, comprising the non-coding RNA 7SK and proteins MePCE and
      LARP7, participates in the regulation of the transcription elongation by RNA
      polymerase II in higher eukaryotes. Binding of a HEXIM protein triggers the
      inhibition of the kinase complex P-TEFb, a key actor of the switch from paused
      transcription to elongation. The present paper reviews what is known about the
      specific recognition of the 7SK RNA by the HEXIM protein. HEXIM uses an arginine
      rich motif (ARM) peptide to bind one specific site in the 5'-hairpin of the 7SK
      RNA. Since HEXIM forms a dimer, what happens with the second ARM impacts the
      assembly symmetry. In order to help sort through possible models, a combination
      of native mass spectrometry and electrophoretic mobility shift assays was used.
      It provides evidence that only one ARM of the HEXIM dimer is directly binding to
      the RNA hairpin and that another sequence downstream of the ARM participates in a
      second binding event allowing the other monomer of HEXIM to bind the RNA. 

PMID- 25863286
TI  - Active site cleft mutants of Os9BGlu31 transglucosidase modify acceptor substrate
      specificity and allow production of multiple kaempferol glycosides.
AB  - BACKGROUND: Rice Os9BGlu31 is a transglucosidase that can transfer glucose to
      phenolic acids, flavonoids, and phytohormones. Os9BGlu31 displays a broad
      specificity with phenolic 1-O-beta-D-glucose esters acting as better glucose
      donors than glucosides, whereas the free phenolic acids of these esters are also
      excellent acceptor substrates. METHODS: Based on homology modeling of this
      enzyme, we made single point mutations of residues surrounding the acceptor
      binding region of the Os9BGlu31 active site. Products of the wild type and mutant
      enzymes in transglycosylation of phenolic acceptors from 4-nitrophenyl beta-D
      glucopyranoside donor were identified and measured by UPLC and negative ion
      electrospray ionization tandem mass spectrometry (LCMSMS). RESULTS: The most
      active variant produced was W243N, while I172T and L183Q mutations decreased the
      activity, and other mutations at W243 (A, D, M, N, F and Y) had variable effects,
      depending on the acceptor substrate. The Os9BGlu31 W243N mutant activity was
      higher than that of wild type on phenolic acids and kaempferol, a flavonol
      containing 4 hydroxyl groups, and the wild type Os9BGlu31 produced only a single
      product from each of these acceptors in significant amounts, while W243 variants
      produced multiple glucoconjugates. Fragmentation analysis provisionally
      identified the kaempferol transglycosylation products as kaempferol 3-O, 7-O, and
      4'-O glucosides and 3,7-O, 4',7-O, and 3,4'-O bis-O-glucosides. The Os9BGlu31
      W243 mutants were also better able to use kaempferol 3-O-glucoside as a donor
      substrate. GENERAL SIGNIFICANCE: The W243 residue was found to be critical to the
      substrate and product specificity of Os9BGlu31 transglucosidase and mutation of
      this residue allows production of a range of glucoconjugates.

PMID- 25863287
TI  - Regulation and RNA-binding properties of Hfq-like RNA chaperones in Bacillus
      anthracis.
AB  - BACKGROUND: Small RNAs (sRNAs) are important modulators of gene expression in
      bacteria. Regulation by sRNAs is yet to be established in Bacillus anthracis.
      Here, regulation and RNA-binding properties of Hfq-like RNA chaperones in B.
      anthracis are investigated. METHODS: Transcript levels were measured by RT-PCR.
      Proteins were cloned, purified, and their ability to bind sRNA was seen by EMSA.
      Regulators of Hfq1 were identified by in silico analysis and validated by EMSA.
      Conserved sRNAs were identified by homology search and their ability to bind Hfq1
      was seen by EMSA. Residues crucial for sRNA binding were identified by mutational
      studies. RESULTS: hfq1 and hfq3 showed expression during exponential phase on BHI
      medium, while hfq2 showed no expression. Hfq1 and Hfq3 formed hexamer and sRNA
      Hfq complex, not Hfq2. In silico prediction and EMSA confirmed AbrB binding to
      the promoter of Hfq1. Homology search identified 7 sRNAs in B. anthracis. The
      sRNA CsfG showed binding to Hfq1 via residues Y24, F29, Q30, R32, K56, and H57.
      CONCLUSIONS: Hfq1 and Hfq3 can function as RNA chaperones in B. anthracis. The
      transition phase repressor AbrB might be responsible for the growth-dependent
      expression of Hfq1. The sporulation-specific sRNA CsfG binds to Hfq1 via its
      distal surface and requires an intact hexameric structure for forming CsfG-Hfq1
      complex. GENERAL SIGNIFICANCE: This is the first report demonstrating the
      regulation and functional properties of Hfq-like RNA chaperones in B. anthracis
      and paves the path towards establishing sRNA-based regulation in B. anthracis.

PMID- 25863288
TI  - A spiking neural network based on the basal ganglia functional anatomy.
AB  - We introduce a spiking neural network of the basal ganglia capable of learning
      stimulus-action associations. We model learning in the three major basal ganglia
      pathways, direct, indirect and hyperdirect, by spike time dependent learning and
      considering the amount of dopamine available (reward). Moreover, we allow to
      learn a cortico-thalamic pathway that bypasses the basal ganglia. As a result the
      system develops new functionalities for the different basal ganglia pathways: The
      direct pathway selects actions by disinhibiting the thalamus, the hyperdirect one
      suppresses alternatives and the indirect pathway learns to inhibit common
      mistakes. Numerical experiments show that the system is capable of learning sets
      of either deterministic or stochastic rules. 

PMID- 25863289
TI  - Further analysis of global MU-stability of complex-valued neural networks with
      unbounded time-varying delays.
AB  - In this paper, we consider the problem of global MU-stability for complex-valued
      neural networks (CVNNs) with unbounded time-varying delays and it has been widely
      investigated. Under mild conditions, some new sufficient conditions for global MU
      stability of considered CVNNs are derived. Moreover, some new sufficient
      conditions are obtained to ensure the global MU-stability of CVNNs in the form of
      complex-valued LMIs as well as real-valued LMIs by using an appropriate Lyapunov
      Krasovskii functional and linear matrix inequalities (LMIs). Both of complex
      valued LMIs as well as real-valued LMIs are easily solved by using standard
      numerical algorithms. Finally, two numerical examples are presented to
      demonstrate the effectiveness and usefulness of our theoretical results. 

PMID- 25863290
TI  - A transcriptome resource for the copepod Calanus glacialis across a range of
      culture temperatures.
AB  - The copepod Calanus glacialis plays a key role in the Arctic pelagic ecosystem.
      Despite its ecological importance and ongoing climate changes, limited knowledge
      at the genomic level has hindered the understanding of the molecular processes
      underlying environmental stress responses and ecological adaptation.
      Transcriptome data was generated from an experiment with C. glacialis copepodite
      (CV) subjected to five different temperatures. We obtained a total of 512,352
      high-quality 454 pyrosequencing reads, which were assembled into 55,562 contigs
      distributed in 128 KEGG pathways. Functional analysis revealed numerous genes
      related to diverse biological functions and processes, including members of all
      major conserved signaling pathways. Comparative analysis of acclimated
      individuals to experimental temperatures has provided information about gene
      variations observed in several pathways (e.g. genes involved in energy, lipid and
      amino acid metabolism were shown to be down-regulated with increasing
      temperatures). These mRNA sequence resources will facilitate further studies on
      genomics and physiology-driven molecular processes in C. glacialis and related
      species. 

PMID- 25863291
TI  - NAD(+)-dependent SIRT1 deactivation has a key role on ischemia-reperfusion
      induced apoptosis.
AB  - Ischemia-reperfusion (IR) leads to severe organ injury and dysfunction. Sirtuins
      (SIRTs) are a family of histone deacetylases (HDACs) that require nicotinamide
      adenine dinucleotide (NAD(+)) for the deacetylation reaction. SIRTs play a major
      role in counteracting cellular stress and apoptosis. This study aimed to
      investigate the mechanisms of heart protection against apoptosis by SIRTs and the
      molecular pathways involved in SIRTs regulation and function in a rat model of IR
      injury. Hearts of male Wistar-Kyoto rats were subjected to 30-min ischemia
      followed by reperfusion up to 6h. IR increased cardiomyocyte apoptosis; the
      cleavage of caspase 3, induced a transient upregulation of SIRT1 and
      downregulation of SIRT6 expression, but decreased SIRT1 activity and reduced
      NAD(+) content. IR also increased forkhead box protein O1 (FoxO1) expression and
      FoxO1 binding to SIRT1 promoter region. Resveratrol restored SIRT1 activity and
      NAD(+) level by an AMPK-dependent mechanism, reduced cardiomyocyte apoptosis, and
      attenuated caspase 3 cleavage via heat shock factor-1 deacetylation and heat
      shock protein (HSP) expression upregulation. Our data show new potential
      molecular mechanisms of up and downstream regulation of SIRT1 in IR. The
      interplay among FoxO1, SIRT1, NAD(+), AMPK, HSP, and SIRT6 depicts a complex
      molecular network that protects the heart from apoptosis during IR and may be
      susceptible to therapeutic interventions. 

PMID- 25863292
TI  - Baroreflex sensitivity and central hemodynamics after omega-3 polyunsaturated
      fatty acids supplementation in an animal model of menopause.
AB  - OBJECTIVE: Baroreflex sensitivity (BRS) and central arterial function are
      significantly worsened after menopausal transition. This study tested the
      hypothesis that administration of n-3 polyunsaturated fatty acids (n-3 PUFA)
      might contribute to prevent these adverse changes in the vascular function of
      ovariectomized rats, an animal model of experimental menopause. METHODS: We
      randomized 30 female Wistar rats, 2months old, into 3 groups: control (CTRL),
      sham surgery, normal diet; ovariectomized with normal diet (OVX) and
      ovariectomized with n-3 PUFA supplementation by daily gavage (0.8g/kg/d)
      (OVX+O3). Two months after surgery, BRS was calculated as the bradycardic
      response to phenylephrine-induced blood pressure increase, while large artery
      function was estimated by the graphical analysis of the aortic pressure wave
      (diastolic to systolic pressure-time integral ratio, DTI/STI). RESULTS:
      Ovariectomy caused a significant decrease in BRS (CTRL: 6.23+/-0.68ms/mmHg; OVX:
      2.85+/-0.75; p<0.001). n-3 PUFA supplementation prevented part of the decline of
      BRS caused by surgical menopause (OVX+O3: 4.75+/-0.53; p<0.01 vs OVX). In animals
      treated with n-3 PUFA, the central arterial pressure profile did not show the
      changes in DTI/STI ratio seen in OVX (OVX: 3.31+/-1.72; OVX+O3: 3.83+/-1.52;
      p<0.01). CONCLUSIONS: In an experimental model of menopause, treatment with n-3
      PUFA normalized central hemodynamics and prevented the decrease in BRS,
      associated with the reduction of compliance of the arterial wall. These findings
      suggest a therapeutic benefit of n-3 PUFA supplementation in the prevention of
      postmenopausal vascular disease.

PMID- 25863293
TI  - Angiopoietin-like 4 serum levels on admission for acute myocardial infarction are
      associated with no-reflow.
AB  - BACKGROUND: No-reflow in ST-segment elevation acute myocardial infarction (STEMI)
      is associated with a poor clinical prognosis. Its pathophysiological mechanisms
      are not fully elucidated yet but enhanced vascular permeability plays a key role
      in this phenomenon. Angiopoietin-like 4 (ANGPTL4) has been implicated in vascular
      permeability in experimental models of acute myocardial infarction (AMI). We
      therefore sought to investigate whether baseline ANGPTL4 serum levels are
      associated with no-reflow after primary percutaneous coronary intervention
      (PPCI). METHODS: We studied a group of 41 patients presenting with a first STEMI
      within 12h of onset of symptoms and who underwent successful PPCI. Blood samples
      were obtained from all patients on admission before the start of the procedure,
      for ANGPTL4 level measurement. No-reflow was assessed by cardiac magnetic
      resonance imaging (MRI), the reference method. RESULTS: MRI-detected no-reflow
      was observed in 20 patients (48.8%). Variables independently associated with no
      reflow on multivariate logistic regression analysis were: lower ANGPTL4 serum
      levels (odds ratio 0.82, 95% CI 0.70-0.98, P=0.02), higher troponin T peak (odds
      ratio 1.03, 95% CI 1.00-1.05, P=0.03), higher incidence of left anterior
      descending coronary artery (LAD) as culprit artery (odds ratio 14.61, 95% CI 1.24
      172.49, P=0.03), and higher C-reactive protein levels (odds ratio 1.18, 95% CI
      1.00-1.39, P=0.05). CONCLUSION: ANGPTL4 serum levels predict MRI-detected no
      reflow after successful PPCI in STEMI patients. Given the recently demonstrated
      therapeutic role of ANGPTL4 in diminishing no-reflow and limiting infarct size in
      pre-clinical animal models, these findings in humans may open up new
      possibilities in the field of research.

PMID- 25863294
TI  - Intracoronary blood sampling with a microcatheter for the diagnosis of giant
      infective coronary aneurysm: Melioidosis of coronary artery mycotic aneurysm.

PMID- 25863295
TI  - Cardiac resynchronization therapy in a patient with percutaneous mitral
      annuloplasty and prior aortic valve surgery.

PMID- 25863297
TI  - Heart donors and Takotsubo syndrome: an apology: Heart donors and Takotsubo
      syndrome.

PMID- 25863296
TI  - Long-term prognosis for individuals with hypertension undergoing coronary artery
      calcium scoring.
AB  - BACKGROUND: To examine the performance of coronary artery calcification (CAC) for
      stratifying long-term risk of death in asymptomatic hypertensive patients.
      METHODS AND RESULTS: 8905 consecutive asymptomatic individuals without
      cardiovascular disease or diabetes who underwent CAC testing (mean age 53.3 +/-
      10.5, 59.3% male) were followed for a mean of 14 years and categorized on the
      background of hypertension as well as age above or below 60 years (in accordance
      with the 2014 Guidelines from the Joint National Committee 8). The prevalence and
      severity of CAC were higher for those with hypertension versus without
      hypertension (P<0.001), and the extent increased proportionally with advancing
      age (P<0.001). Following adjustment, the presence of CAC in hypertensive with
      respect to normotensive, was associated with worse prognosis for individuals
      above the age of 60 years (HR 7.74 [95% CI: 5.15-11.63] vs. HR 4.83 [95% CI: 3.18
      7.33]) than individuals below the age of 60 (HR 3.18 [95% CI: 2.42-4.19] vs. HR
      2.14 [95% CI: 1.61-2.85]), respectively. A zero CAC score in hypertensive over
      the age of 60 years was associated with a lower but persisting risk of mortality
      for (HR 2.48 [95% CI: 1.50-4.08]) that was attenuated non-significant for those
      below the age of 60 years (P=0.09). In a "low risk" hypertensive population, the
      presence any CAC was associated with an almost five-fold (HR 4.68 [95% CI: 2.22
      9.87]) increased risk of death. CONCLUSION: The presence and extent of CAC
      effectively may help the clinicians to further discriminate the long-term risk of
      mortality among asymptomatic hypertensive individuals, beyond conventional
      cardiovascular risk and current guidelines.

PMID- 25863298
TI  - Ethnic variations in length of hospital stay in patients with atrial
      fibrillation.

PMID- 25863299
TI  - Three-dimensional guided renal denervation: Carrying coals to Newcastle?

PMID- 25863300
TI  - Neighborhood deprivation and warfarin, aspirin and statin prescription - A cohort
      study of men and women treated for atrial fibrillation in Swedish primary care.
AB  - BACKGROUND: We aimed to study differences in the prescribing of warfarin, aspirin
      and statins to patients with atrial fibrillation (AF) in socio-economically
      diverse neighborhoods. We also aimed to explore the effects of neighborhood
      deprivation on the relationship between CHADS2 risk score and warfarin
      prescription. METHODS: Data were obtained from primary health care records that
      contained individual clinical data that were linked to national data on
      neighborhood of residence and a deprivation index for different neighborhoods.
      Logistic regression was used to estimate the potential neighborhood differences
      in prescribed warfarin, aspirin and statins, and the association between the
      CHADS2 score and prescribed warfarin treatment, in neighborhoods with high,
      middle (referent) and low socio-economic (SES). RESULTS: After adjustment for
      age, socio-economic factors, co-morbidities and moves to neighborhoods with
      different SES during follow-up, adults with AF living in high SES neighborhoods
      were more often prescribed warfarin (men odds ratio (OR) (95% confidence interval
      (CI): 1.44 (1.27-1.62); and women OR (95% CI): 1.19 (1.05-1.36)) and statins (men
      OR (95% CI): 1.23 (1.07-1.41); women OR (95% CI): 1.23 (1.05-1.44)) compared to
      their counterparts residing in middle SES. Prescription of aspirin was lower in
      men from high SES neighborhoods (OR (95% CI): 0.75 (0.65-0.86)) than in those
      from middle SES neighborhoods. Higher CHADS2 risk scores were associated with
      higher warfarin prescription which remained after adjustment for neighborhood
      SES. CONCLUSIONS: The apparent inequalities in pharmacotherapy seen in the
      present study call for resource allocation to primary care in neighborhoods with
      low and middle socio-economic status.

PMID- 25863301
TI  - Afternoon nap and nighttime sleep with risk of micro- and macrovascular disease
      in middle-aged and elderly population.

PMID- 25863302
TI  - Account should also have been taken of the harm versus benefit of aspirin use.

PMID- 25863303
TI  - Heart rate variability, but not heart rate, is associated with handgrip strength
      and mortality in older Africans at very low cardiovascular risk: A population
      based study.

PMID- 25863304
TI  - Percutaneous coronary intervention driven by combined use of intracoronary
      anatomy and physiology: Towards a tailored therapy for coronary artery disease.

PMID- 25863305
TI  - Non-invasive assessment of low risk acute chest pain in the emergency department:
      A comparative meta-analysis of prospective studies.
AB  - BACKGROUND: The aim of this meta-analysis was to compare the diagnostic accuracy
      of cardiac computed tomographic angiography (CCTA), stress echocardiography (SE)
      and radionuclide single photon emission computed tomography (SPECT) for the
      assessment of chest pain in emergency department (ED) setting. METHODS: A
      systematic review of Medline, Cochrane and Embase was undertaken for prospective
      clinical studies assessing the diagnostic efficacy of CCTA, SE or SPECT, as
      compared to intracoronary angiography (ICA) or the later presence of major
      adverse clinical outcomes (MACE), in patients presenting to the ED with chest
      pain. Standard approach and bivariate analysis were performed. RESULTS: Thirty
      seven studies (15 CCTA, 9 SE, 13 SPECT) comprising a total of 7800 patients
      fulfilled inclusion criteria. The respective weighted mean sensitivity,
      specificity, positive predictive value (PPV), negative predictive value (NPV) and
      total diagnostic accuracy for CCTA were: 95%, 99%, 84%, 100% and 99%, for SE
      were: 84%, 94%, 73%, 96% and 96%, and for SPECT were: 85%, 86%, 57%, 95% and 88%.
      There was no significant difference between modalities in terms of NPV. Bivariate
      analysis revealed that CCTA had statistically greater sensitivity, specificity,
      PPV and overall diagnostic accuracy when compared to SE and SPECT. CONCLUSIONS:
      All three modalities, when employed by an experienced clinician, are highly
      accurate. Each has its own strengths and limitations making each well suited for
      different patient groups. CCTA has higher accuracy than SE and SPECT, but it has
      many drawbacks, most importantly its lack of physiologic data.

PMID- 25863306
TI  - Dextrocardia and symmetric hypertrophic cardiomyopathy with multiple mutations of
      genes encoding the sarcomere proteins.

PMID- 25863307
TI  - Molecular pathogenesis of Marfan syndrome.
AB  - Marfan syndrome (MFS) is a genetic disorder that affects multiple organs.
      Mortality imposed by aortic aneurysm and dissections represent the most serious
      clinical manifestation of MFS. Progressive pathological aortic root enlargement
      as the result of degeneration of microfibril architecture and consequential loss
      of extracellular matrix integrity due to fibrillin-1 (FBN1) mutations are
      commonly diagnosed clinical manifestations of MFS. However, overlapping clinical
      manifestations with other aneurysmal disorders present a significant challenge in
      early and accurate diagnosis of MFS. While FBN1 mutations, abnormal transforming
      growth factor-beta signaling and dysregulated matrix metalloproteinases have been
      implicated in MFS, clinically accepted risk-stratifying biomarkers have yet to be
      reliably identified. In this review, we summarize current consensus and recent
      insights in the understanding of MFS pathogenesis. Finally, we introduce the
      application of induced pluripotent stem cells (iPSCs) as cellular models for MFS
      and its potential as a novel platform into providing better appreciation of
      mechanisms underlying MFS diverse manifestations in the cardiovascular system. 

PMID- 25863308
TI  - Embolic protection devices during carotid artery stenting: Is there a difference
      between proximal occlusion and distal filter?

PMID- 25863309
TI  - Six month angiographic result of supplementary paclitaxel-eluting balloon
      deployment to treat side branch ostium narrowing (SARPEDON).

PMID- 25863310
TI  - Arterial stiffness response to exercise training: Unequivocal explanations?

PMID- 25863311
TI  - Microbiota and probiotics in canine and feline welfare.
AB  - Dogs and cats have been cohabiting with us for thousands of years. They are the
      major human companions. Today, dogs and cats live in urban areas. Cats and most
      dogs are on high carbohydrate diets and face similar life-style challenges as the
      human beings. The health and well-being of companion animals, just as their
      owners, depends on the gut microbes. Providing a proper care and nutritionally
      balanced diet to companion animals is recognised as a part of our responsibility
      to maintain the health and well being of our pet. However, as microbiota
      differences may facilitate exposure to pathogens and harmful environmental
      influences, it is prudent to search for novel tools to protect dogs and cats and
      at the same time the human owners from pathogens. Specific probiotic strains
      and/or their defined combinations may be useful in the canine and feline
      nutrition, therapy, and care. Probiotic supplementations have been successful in
      the prevention and treatment of acute gastroenteritis, treatment of IBD, and
      prevention of allergy in companion animals. New challenges for probiotic
      applications include maintenance of obesity and overweight, urogenital tract
      infections, Helicobacter gastritis and parasitic infections. The probiotics of
      human origin appear to be among the new promising tools for the maintenance of
      pets' health. However, the host-derived microorganisms might be the most
      appropriate probiotic source. Therefore, more controlled trials are needed to
      characterise new and safe probiotic preparations with an impact on general health
      and well being as well as health maintenance in dogs and cats. 

PMID- 25863312
TI  - Synergistic inhibition of Clostridium difficile with nisin-lysozyme combination
      treatment.
AB  - Clostridium difficile vegetative cells were not inhibited completely after a 120
      min treatment with 40 nM nisin or 0.8 mM lysozyme. However, these cells were
      completely inhibited after only a 30-min incubation with both 20 nM nisin and 0.2
      mM lysozyme. 

PMID- 25863313
TI  - Hydrological simulation of Po River (North Italy) discharge under climate change
      scenarios using the RCM COSMO-CLM.
AB  - The impacts of climate change on Po River discharges are investigated through a
      set of climate, hydrological, water-balance simulations continuous in space and
      time. Precipitation and 2m mean temperature fields from climate projections under
      two different representative concentration pathways, RCP4.5 and RCP8.5, have been
      used to drive the hydrological model. Climate projections are obtained nesting
      the regional climate model COSMO-CLM into the global climate model CMCC-CM. The
      bias in climate projections is corrected applying the distribution derived
      quantile mapping. The persistence of climate signal in precipitation and
      temperature after the bias correction is assessed in terms of climate anomaly for
      2041-2070 and 2071-2100 periods versus 1982-2011. To account for the overall
      uncertainty of emission scenarios, climate models and bias correction, the
      hydrological/water balance simulations are carried out using both raw and bias
      corrected climate datasets. Results show that under both RCPs, either considering
      raw and bias corrected climate datasets, temperature is expected to increase on
      the whole Po River basin and in all the seasons; the most significant changes in
      precipitation and discharges occur in summer, when the reduction of precipitation
      leads to an increase in low flow duration and occurrence likelihood, and in
      autumn and winter where precipitation shows a positive variation increasing the
      high flows frequency. 

PMID- 25863314
TI  - Assessment of human exposure to environmental sources of nickel in Europe:
      Inhalation exposure.
AB  - The paper describes the inhalation nickel (Ni) exposure of humans via the
      environment for the regional scale in the EU, together with a tiered approach for
      assessing additional local exposure from industrial emissions. The approach was
      designed, in the context of REACH, for the purpose of assessing and controlling
      emissions and air quality in the neighbourhood of Ni producers and downstream
      users. Two Derived No Effect Level (DNEL) values for chronic inhalation exposure
      to total Ni in PM10 (20 and 60ngNi/m(3)) were considered. The value of
      20ngNi/m(3) is the current EU air quality guidance value. The value of
      60ngNi/m(3) is derived here based on recently published Ni data (Oller et al.,
      2014). Both values are protective for respiratory toxicity and carcinogenicity
      but differ in the application of toxicokinetic adjustments and cancer threshold
      considerations. Estimates of air Ni concentrations at the European regional scale
      were derived from the database of the European Environment Agency. The 50th and
      90th percentile regional exposures were below both DNEL values. To assess REACH
      compliance at the local scale, measured ambient air data are preferred but are
      often unavailable. A tiered approach for the use of modelled ambient air
      concentrations was developed, starting with the application of the default EUSES
      model and progressing to more sophisticated models. As an example, the tiered
      approach was applied to 33 EU Ni sulphate producers' and downstream users' sites.
      Applying the EUSES model demonstrates compliance with a DNEL of 60ngNi/m(3) for
      the majority of sites, while the value of the refined modelling is demonstrated
      when a DNEL of 20ngNi/m(3) is considered. The proposed approach, applicable to
      metals in general, can be used in the context of REACH, for refining the risk
      characterisation and guiding the selection of risk management measures. 

PMID- 25863315
TI  - Ethnopedology and soil quality of bamboo (Bambusa sp.) based agroforestry system.
AB  - It is widely recognized that farmers' hold important knowledge of folk soil
      classification for agricultural land for its uses, yet little has been studied
      for traditional agroforestry systems. This article explores the ethnopedology of
      bamboo (Bambusa sp.) based agroforestry system in North East India, and
      establishes the relationship of soil quality index (SQI) with bamboo
      productivity. The study revealed four basic folk soil (mati) types: kalo (black
      soil), lal (red soil), pathal (stony soil) and balu (sandy soil). Of these, lal
      mati soil was the most predominant soil type (~ 40%) in bamboo-based agroforestry
      system. Soil physio-chemical parameters were studied to validate the farmers'
      soil hierarchal classification and also to correlate with productivity of the
      bamboo stand. Farmers' hierarchal folk soil classification was consistent with
      the laboratory scientific analysis. Culm production (i.e. measure of productivity
      of bamboo) was the highest (27culmsclump(-1)) in kalo mati (black soil) and the
      lowest (19culmsclump(-1)) in balu mati (sandy soil). Linear correlation of
      individual soil quality parameter with bamboo productivity explained 16 to 49% of
      the variability. A multiple correlation of the best fitted linear soil quality
      parameter (soil organic carbon or SOC, water holding capacity or WHC, total
      nitrogen) with productivity improved explanatory power to 53%. Development of SQI
      from ten relevant soil quality parameters and its correlation with bamboo
      productivity explained the 64% of the variation and therefore, suggest SQI as the
      best determinant of bamboo yield. Data presented indicate that the kalo mati
      (black soil) is sustainable or sustainable with high input. However, the other
      three folk soil types (red, stony and sandy soil) are also sustainable but for
      other land uses. Therefore, ethnopedological studies may move beyond routine
      laboratory analysis and incorporate SQI for assessing the sustainability of land
      uses managed by the farmers'. Additional research is required to incorporate
      principal component analysis for improving the SQI and site potential assessment.
      It is also important to evaluate the minimum data set (MDS) required for SQI and
      productivity assessment in agroforestry systems. 

PMID- 25863316
TI  - Estrogenic environmental contaminants alter the mRNA abundance profiles of genes
      involved in gonadal differentiation of the American bullfrog.
AB  - Wildlife and human populations are exposed to anthropogenic mixtures of chemicals
      in the environment that may adversely influence normal reproductive function and
      development. We determined the effects of exposure to estrogenic chemicals and
      wastewater effluent (WWE) on developing gonads of the American bullfrog, Rana
      (Lithobates) catesbeiana, a species whose widespread distribution make it an
      ideal model for environmental monitoring of endocrine effects of chemical
      contaminants. Premetamorphic bullfrog tadpoles were exposed to treatment vehicle,
      17beta-estradiol (E2; 10(-9)M) or 4-tert-octylphenol (OP; 10(-9)M, 10(-8)M, and
      10(-7)M). Additionally, gonadal differentiation was evaluated in bullfrog
      tadpoles from a WWE-containing site versus those from a reference location
      receiving no WWE. In both studies, phenotypic sex, steroidogenic factor-1
      (nr5a1), and aromatase (cyp19a1) mRNA levels using quantitative real-time PCR
      were determined. Exposure to E2 or OP did not alter sex ratios. In controls, both
      nr5a1 and cyp19a1 transcript levels exhibited sexual dimorphism, with males
      demonstrating higher levels of nr5a1 and females greater abundance of cyp19a1.
      However, E2 exposure increased cyp19a1 mRNA abundance in testes and decreased
      levels in ovaries, eliminating the sexual dimorphism observed in controls. E2
      exposed males exhibited increased nr5a1 transcript levels in the testes compared
      to controls, while females demonstrated no E2 effect. OP treatment had no effect
      on female cyp19a1 mRNA abundance, but exposure to 10(-7)M OP increased testicular
      transcript levels. Treatment with 10(-9) and 10(-8)M OP, but not 10(-7)M,
      resulted in decreased abundance of nr5a1 transcript in both ovaries and testes.
      Animals from the field had sexually dimorphic gonadal levels of cyp19a1, but both
      sexes from the WWE site exhibited elevated cyp19a1 transcript abundance compared
      to the reference location. Individual chemical compounds and anthropogenic
      wastewater effluent dispersed within the environment influence the levels of
      gonadal mRNA encoding key proteins involved in gonadal differentiation. 

PMID- 25863317
TI  - Environmental response of an Irish estuary to changing land management practices.
AB  - Anthropogenic pressures have led to problems of nutrient over-enrichment and
      eutrophication in estuarine and coastal systems on a global scale. Recent
      improvements in farming practices, specifically a decrease in fertiliser
      application rates, have reduced nutrient loadings in Ireland. In line with
      national and European Directives, monitoring of Irish estuarine systems has been
      conducted for the last 30years, allowing a comparison of the effectiveness of
      measures undertaken to improve water quality and chemical and biological trends.
      The Blackwater Estuary, which drains a large agricultural catchment on the south
      coast of Ireland, has experienced a decrease in calculated nitrogen (N) (17%) and
      phosphorus (P) (20%) loads in the last decade. Monitored long-term river inputs
      reflect the reductions while estuarine P concentrations, chlorophyll and
      dissolved oxygen saturation show concurrent improvement. Consistently high N
      concentrations suggest a decoupling between N loads and estuarine responses. This
      highlights the complex interaction between N and P load reductions, and
      biochemical processes relating to remineralisation and primary production which
      can alter the effectiveness of the estuarine filter in reducing nutrient
      transport to the coastal zone. Effective management and reduction of both diffuse
      and point nutrient sources to surface waters require a consideration of the
      processes which may alter the effectiveness of measures in estuarine and coastal
      waters. 

PMID- 25863318
TI  - In situ assessment of phyto and zooavailability of trace elements: A
      complementary approach to chemical extraction procedures.
AB  - For an accurate risk assessment of sites contaminated by trace elements (TE),
      measurements of bioavailability must be performed. This is routinely achieved
      using the standardized 0.01M CaCl2 method. However, the suitability of chemical
      extractions as proxies of bioavailability is questionable. We analyzed the
      correlations between chemically estimated TE bioavailability and TE actually
      accumulated by coupling plant and snails bioindicators. Results showed a better
      correlation between plant TE contents and CaCl2 fraction while total soil
      concentration better explained snail TE contents. However in both cases chemical
      measures were not suitable to predict TE accumulation and bioavailability.
      Considering the soil properties only improve the estimation of Cr, Ni and Pb
      accumulation by plants while for snails, TE contents in viscera were dependent
      both on soil and plant contents and soil properties. It highlights the
      complementarities of biomonitoring methods to assess bioavailability. This dual
      approach allows a "physiologically defined" evaluation of bioavailability. 

PMID- 25863319
TI  - Nitrogen availability influences phosphorus removal in microalgae-based
      wastewater treatment.
AB  - Microalgae offer a promising technology to remove and re-use the nutrients N and
      P from wastewater. For effective removal of both N and P, it is important that
      microalgae can adjust the N and P concentration in their biomass to the N and P
      supply in the wastewater. The aim of this study was to evaluate to what extent
      microalgae can adjust the N and P concentrations in their biomass to the N and P
      supply in the wastewater, and to what extent supply of one nutrient influences
      the removal of the other nutrient. Using Chlorella and Scenedesmus as model
      organisms, we quantified growth and biomass composition in medium with different
      initial N and P concentrations in all possible combinations. Nutrient supply
      marginally affected biomass yield of both microalgae but had a strong influence
      on the composition of the biomass. The nutrient concentrations in the biomass
      ranged 5.0-10.1 % for N and 0.5-1.3 % for P in Chlorella and 2.9-8.4 % for N and
      0.5-1.7 % for P in Scenedesmus. The concentrations of P in the biomass remained
      low and were relatively constant (0.6-0.8 % P) when the N concentration in the
      biomass was low. As a result, removal of P from the wastewater was influenced by
      the concentration of N in the wastewater. When the initial N concentration in the
      wastewater was above 40 mg L(-1) the microalgae could remove up to 6 mg P L(-1),
      but this removal was only 2 mg P L(-1) when the initial N concentration was below
      20 mg L(-1). A lower N supply increased the carbohydrate concentration to about
      40% and lipid concentration to about 30% for both species, compared to around 15%
      and 10% respectively at high N supply. Our results show that sufficiently high N
      concentrations are needed to ensure effective P removal from wastewater due to
      the positive effect of N on the accumulation of P.

PMID- 25863320
TI  - Pipette tip solid-phase extraction and high-performance liquid chromatography for
      the determination of flavonoids from Epimedii herba in rat serum and application
      of the technique to pharmacokinetic studies.
AB  - Epimedii herba is a traditional Chinese medicine for the treatment of
      osteoporosis. Epimedin A, B and C and icariin are the primary effective
      ingredients of this medicine. In this study, a simple and low-cost method based
      on pipette tip solid-phase extraction, high-performance liquid chromatography
      separation, and diode array detection has been developed for the simultaneous
      analysis of four flavonoids (epimedin A, B and C and icariin) from Epimedii herba
      in rat serum samples. In this novel extraction configuration, the sorbents were
      placed between a filter (hollow fiber) and the pipette tip. Pipette tip solid
      phase extraction has several advantages compared to conventional extraction
      methods: faster extraction time (6.0min); lower sample volume (100MUL); lower
      solvent volume (100MUL); and less solvent waste. Under the optimum extraction
      conditions, the method showed good linearity (0.05-10.0MUgmL(-1)), acceptable
      intra- and inter precision (RSD<6%), low limits of quantification (0.027
      0.045MUgmL(-1)) and satisfactory relative recoveries (98.63-103.18%). This method
      was successfully applied to investigate the pharmacokinetics of the major
      flavonoids in Epimedii herba extract after oral administration to rats (10gkg(-1)
      body weight). The primary pharmacokinetic parameters for rats were determined as
      follows: Cmax, 0.45-4.11MUgmL(-1); Tmax, 0.21-0.26h; t1/2alpha, 0.06-0.12h;
      t1/2beta, 2.02-3.48h; AUC0-infinity: 0.50-2.58MUghmL(-1); CL, 19.53-44.72Lkg(
      1)h(-1); and MRT0-infinity, 2.25-3.77h. The developed method has the potential to
      promulgate the pharmacokinetics and provide more information for clinical
      applications. 

PMID- 25863321
TI  - A GIS typology to locate sites of submarine groundwater discharge.
AB  - Although many researchers agree on the importance of submarine groundwater
      discharge (SGD), it remains difficult to locate and quantify this process. A
      groundwater typology was developed based on local digital elevation models and
      compared to concurrent radon mapping indicative of SGD in the Niantic River, CT
      USA. Areas of high radon activity were located near areas of high flow
      accumulation lending evidence to the utility of this approach to locate SGD. The
      benefits of this approach are three-fold: fresh terrestrial SGD may be quickly
      located through widely-available digital elevation models at little or no cost to
      the investigator; fresh SGD may also be quantified through the GIS approach by
      multiplying pixelated flow accumulation with the expected annual recharge; and,
      as these data necessarily quantify only fresh SGD, a comparison of these data
      with SGD as calculated by Rn activity may allow for the separation of the fresh
      and circulated fractions of SGD. This exercise was completed for the Niantic
      River where SGD as calculated by the GIS model is 1.2 m(3)/s, SGD as calculated
      by Rn activity is 0.73-5.5 m(3)/s, and SGD as calculated via a theoretical
      approach is 1.8-4.3 m(3)/s. Therefore fresh, terrestrial SGD accounts for 22-100%
      of total SGD in the Niantic River. 

PMID- 25863322
TI  - High radon levels in subterranean environments: monitoring and technical criteria
      to ensure human safety (case of Castanar cave, Spain).
AB  - Castanar cave contains the highest radon gas ((222)Rn) concentration in Spain
      with an annual average of 31.9 kBq m(-)(3). Seasonal variations with summer
      minimums and maximum values in fall were recorded. The reduction of air-filled
      porosity of soil and rock by condensation or rainfalls hides the radon exchange
      by gas diffusion, determining this seasonal stair-step pattern of the radon
      activity concentration in underground air. The effective total dose and the
      maximum hours permitted have been evaluated for the guides and public safety with
      a highly detailed radon measurement along 2011 and 2012. A network of 12 passive
      detectors (kodalphas) has been installed, as well as, two radon continuous
      monitoring in the most interesting geological sites of the subterranean
      environment. A follow up of the recommended time (max. 50 min) inside the
      underground environment has been analysed since the reopen to public visitors for
      not surpassing the legal maximum effective dose for tourists and guides. Results
      shown that public visitors would receive in fall a 12.1% of the total effective
      dose permitted per visit, whereas in summer it is reduced to 8.6%, while the cave
      guide received a total effective dose of 6.41 mSv in four months. The spatial
      radon maps allow defining the most suitable touristic paths according to the
      radon concentration distribution and therefore, appropriate fall and summer
      touristic paths are recommended. 

PMID- 25863323
TI  - Simulation of radioactive plume gamma dose over a complex terrain using
      Lagrangian particle dispersion model.
AB  - FLEXPART-WRF is a versatile model for the simulation of plume dispersion over a
      complex terrain in a mesoscale region. This study deals with its application to
      the dispersion of a hypothetical air borne gaseous radioactivity over a
      topographically complex nuclear site in southeastern France. A computational
      method for calculating plume gamma dose to the ground level receptor is
      introduced in FLEXPART using the point kernel method. Comparison with another
      similar dose computing code SPEEDI is carried out. In SPEEDI the dose is
      calculated for specific grid sizes, the lowest available being 250 m, whereas in
      FLEXPART it is grid independent. Spatial distribution of dose by both the models
      is analyzed. Due to the ability of FLEXPART to utilize the spatio-temporal
      variability of meteorological variables as input, particularly the height of the
      PBL, the simulated dose values were higher than SPEEDI estimates. The FLEXPART
      WRF in combination with point kernel dose module gives a more realistic picture
      of plume gamma dose distribution in a complex terrain, a situation likely under
      accidental release of radioactivity in a mesoscale range. 

PMID- 25863324
TI  - Improved lignin pyrolysis for phenolics production in a bubbling bed reactor-
      Effect of bed materials.
AB  - Lignin pyrolysis was studied in a bubbling fluidized bed reactor equipped with a
      fractional condensation train, using nitrogen as the fluidization gas. The effect
      of different bed materials (silica sand, lignin char, activated lignin char,
      birch bark char, and foamed glass beads) on bio-oil yield and quality was
      investigated for a pyrolysis temperature of 550  degrees C. Results how that a
      bed of activated lignin char is preferable to the commonly used silica sand:
      pyrolysis of Kraft lignin with a bed of activated lignin char not only provides a
      pure char product, but also a higher dry bio-oil yield (with a relative increase
      of 43%), lower pyrolytic water production, and better bio-oil quality. The bio
      oil obtained from Kraft lignin pyrolysis with a bed of activated lignin char has
      a lower average molecular weight, less tar, more phenolics, and less acidity than
      when sand is used as bed material.

PMID- 25863325
TI  - WITHDRAWN: Fascicle switching: a conserved pattern of axogenesis in the
      panarthropod brain.
AB  - The Publisher regrets that this article is an accidental duplication of an
      article that has already been published,
      http://dx.doi.org10.1016/j.asd.2014.11.003. The duplicate article has therefore
      been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at
      http://www.elsevier.com/locate/withdrawalpolicy.

PMID- 25863326
TI  - Spermatodesm reorganization in the spermatophore and in the spermatheca of the
      bushcricket Tylopsis liliifolia (Fabricius) (Orthoptera, Tettigoniidae).
AB  - Spermatozoa of Tettigoniidae are usually transferred to the female by means of a
      spermatophore which is also the site of feather-shaped spermatodesm formation.
      These spermatodesms are then transferred to a spermatheca, composed of a
      spermathecal duct and of a seminal receptacle, involved in storing spermatozoa.
      In order to extend the knowledge about sperm transfer and spermatodesms
      reorganization in the Tettigoniidae, a morpho-structural investigation was
      carried out on spermatophore and spermatheca of Tylopsis liliifolia and on the
      reorganization of the gametes from the spermatophore. Our results show that the
      spermatodesms undergo disorganization in the spermatophore; unlike other
      Tettigoniidae, however, feather-shaped spermatodesms are never found. The
      epithelium of the spermatheca consists of two cell types, the cuticle-forming and
      the gland cells, with secretory features. The gland cells, absent in the distal
      tract of the seminal receptacle, release their secretion in a "reservoir" where
      an efferent duct opens. In the distal tract of the spermathecal duct, adjacent
      epithelial cells show diversified ultrastructural characteristics whose probable
      role is discussed. A particular feature of T. liliifolia is the genesis of the
      feather-shaped spermatodesms in the seminal receptacle. This feature and the
      peculiar organization of the feather-shaped spermatodesm are a possible
      autapomorphy of T. liliifolia. 

PMID- 25863327
TI  - Bioaccumulation and detoxification responses in the scallop Chlamys farreri
      exposed to tetrabromobisphenol A (TBBPA).
AB  - Tetrabromobisphenol A (TBBPA) is currently the most widely used brominated flame
      retardant (BFR). In this study, the bioaccumulation of TBBPA and its consequent
      detoxification responses were examined in the scallop Chlamys farreri over 10
      days' exposure. Chemical analysis showed that C. farreri absorbed TBBPA rapidly
      and an approximate steady state was achieved within 6 days. The mRNA expression
      levels of three important genes involved in aryl hydrocarbon receptor (AhR)
      pathway were down-regulated upon TBBPA exposure. Both CYP3A and CYP4 showed time
      dependent responses to TBBPA exposure. Glutathione-S-transferase (GST) activity
      and gene expression level, and UDP-glucuronosyltransferase (UGT) activity were
      increased in time- and dose-dependent manners, confirming their role in the phase
      II metabolism of TBBPA. The TBBPA-elicited down-regulation of the P-glycoprotein
      (Pgp) gene was observed in all treatments. This study provides a preliminary
      basis for studying TBBPA detoxification mechanisms of marine bivalves. 

PMID- 25863328
TI  - Effects of lead nitrate and sodium selenite on DNA damage and oxidative stress in
      diabetic and non-diabetic rat erythrocytes and leucocytes.
AB  - The adverse effects of lead nitrate (LN) and the preventive role of sodium
      selenite were investigated in diabetic and non-diabetic rat blood by measuring
      trolox equivalent antioxidant capacity (TEAC), ferric reducing antioxidant power
      (FRAP), malondialdehyde (MDA) levels and activities of superoxide dismutase
      (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione-S-transferase
      (GST) also by evaluating DNA damage with comet assay. LN increased the levels of
      MDA, tail DNA%, mean tail length and tail moment, decreased the enzymes
      activities, FRAP and TEAC values. In sodium selenite+LN group, we observed the
      protective effect of sodium selenite on examining parameters. Diabetes caused
      alterations on these parameters, too. We found that sodium selenite did not
      protect against diabetes caused damages. As a result, LN caused toxic effects on
      blood cells and sodium selenite alleviated this toxicity but it did not show
      preventive effect against diabetes. Also, LN caused more harmfull effects in
      diabetic groups than non-diabetic groups. 

PMID- 25863329
TI  - Activation of HSPA1A promoter by environmental pollutants: An early and rapid
      response to cellular damage.
AB  - We established the HepG2-luciferase cells containing a luciferase reporter gene
      regulated by human HSPA1A promoter. The screening of heat shock and three typical
      environmental toxicants revealed differences in their capacities to activate
      HSPA1A promoter in HepG2-luciferase cells. After heat shock, a progressive time
      dependent increase in relative luciferase activity was detected peaking at 8h of
      recovery. Benzo[a]pyrene, formaldehyde and sodium bisulfite induced significant
      time-dependent elevation of relative luciferase activity, which were positively
      correlated with MDA concentration, Olive tail moment and micronuclei frequency.
      The significant increase in relative luciferase activity was already evident
      after 4h of benzo[a]pyrene, 1h of formaldehyde and sodium bisulfite exposure,
      when no increases in cellular damage were detected by other toxicity tests.
      Therefore, the HepG2-luciferase cells are useful model for examining the overall
      cellular responses to oxidative stress and genotoxic damage, and provide a
      reporter system for rapid and sensitive screening of environmental pollutants. 

PMID- 25863330
TI  - Function of respiratory system evaluated using selected spirometry parameters in
      persons occupationally exposed to lead without evident health problems.
AB  - This study aimed at evaluation of selected spirometric parameters in persons
      occupationally exposed to lead without evident health problems. The studies were
      conducted on 69 men occupationally exposed to lead. Occupational exposure to lead
      was characterized by estimation of blood lead concentration (Pb-B) and blood zinc
      protoporphyrin concentration (ZnPP). Function of respiratory system was examined
      using spirometric analysis with evaluation of its basic parameters: forced vital
      capacity (FVC), forced expiratory volume (in 1s) (FEV1), Tiffeneau index
      (FEV1%VC) and peak expiratory flow (PEF). In the study group negative linear
      correlations were documented between Pb-B and FVC, FEV 1 and FEV1%VC. A more
      pronounced age, higher values of BMI and higher blood lead concentration
      constituted independent risk factors for reduced FEV1%VC. CONCLUSION: Persons
      occupationally exposed to lead with elevated blood lead concentration and blood
      zinc protoporphyrin concentration manifested the impaired function of respiratory
      system, evaluated using parameters of spirometry.

PMID- 25863331
TI  - Benzo(a)pyrene-induced cytochrome p4501A expression of four freshwater fishes
      (Oryzias latipes, Danio rerio, Cyprinus carpio, and Zacco platypus).
AB  - Oryzias latipes, Danio rerio, Cyprinus carpio, and Zacco platypus are useful
      indicator species for CYP1A biomarker studies; however, comparative studies have
      not been performed. To compare susceptibility, dose- and time-dependent CYP1A
      induction at the mRNA and protein levels in response to benzo(a)pyrene (BaP)
      exposure was analyzed. At the mRNA level, a statistically significant difference
      was found among the four species; however, such was not observed at the protein
      level. C. carpio showed the highest CYP1A induction level and the steepest slope
      in the dose-response curve. To assess susceptibility, the difference in CYP1A
      mRNA induction among species must be considered, and C. carpio was the most
      sensitive species of the four evaluated in terms of CYP1A expression. 

PMID- 25863332
TI  - Subacute and subchronic toxicity of Avalon((r)) mixture (bentazone+dicamba) to
      rats.
AB  - Subacute and subchronic toxicity of the herbicide Avalon((r)), a mixture of
      bentazone and dicamba, were tested on rats. Avalon((r)) was administered at dose
      levels of 250, 500 and 1000mg/kg body weight/day for 28 and 90 days. Alanine
      aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase
      (ALP) activities were monitored together with biochemistry parameters. The
      results showed that the mixture caused increases in the activities of ALT, AST
      and ALP, elevated concentrations of sodium, albumin and albumin/globulin ratio in
      males. In females, ALT activity, cholesterol and phosphate levels were increased.
      The changes generally were dose related and, in most cases, females exhibited
      lower susceptibility than males. The effects of a mixture are, in the most cases,
      different from the effects of the individual substances. The effects of bentazone
      were not prevalent which would be expected taking the composition of the mixture
      into account. 

PMID- 25863333
TI  - Woods: A fast and accurate functional annotator and classifier of genomic and
      metagenomic sequences.
AB  - Functional annotation of the gigantic metagenomic data is one of the major time
      consuming and computationally demanding tasks, which is currently a bottleneck
      for the efficient analysis. The commonly used homology-based methods to
      functionally annotate and classify proteins are extremely slow. Therefore, to
      achieve faster and accurate functional annotation, we have developed an orthology
      based functional classifier 'Woods' by using a combination of machine learning
      and similarity-based approaches. Woods displayed a precision of 98.79% on
      independent genomic dataset, 96.66% on simulated metagenomic dataset and >97% on
      two real metagenomic datasets. In addition, it performed >87 times faster than
      BLAST on the two real metagenomic datasets. Woods can be used as a highly
      efficient and accurate classifier with high-throughput capability which
      facilitates its usability on large metagenomic datasets. 

PMID- 25863334
TI  - Predicting high-grade cancer at ten-core prostate biopsy using four kallikrein
      markers measured in blood in the ProtecT study.
AB  - BACKGROUND: Many men with elevated prostate-specific antigen (PSA) levels in
      serum do not have aggressive prostate cancer and undergo unnecessary biopsy.
      Retrospective studies using cryopreserved serum suggest that four kallikrein
      markers can predict biopsy outcome. METHODS: Free, intact and total PSA, and
      kallikrein-related peptidase 2 were measured in cryopreserved blood from 6129 men
      with elevated PSA (>=3.0ng/mL) participating in the prospective, randomized trial
      Prostate Testing for Cancer and Treatment. Marker levels from 4765 men providing
      anticoagulated plasma were incorporated into statistical models to predict any
      grade and high-grade (Gleason score >=7) prostate cancer at 10-core biopsy. The
      models were corrected for optimism by 10-fold cross validation and independently
      validated using markers measured in serum from 1364 men. All statistical tests
      were two-sided. RESULTS: The four kallikreins enhanced prostate cancer detection
      compared with PSA and age alone. Area under the curve (AUC) for the four
      kallikreins was 0.719 (95% confidence interval [CI] = 0.704 to 0.734) vs 0.634
      (95% CI = 0.617 to 0.651, P < .001) for PSA and age alone for any-grade cancer,
      and 0.820 (95% CI = 0.802 to 0.838) vs 0.738 (95% CI = 0.716 to 0.761) for high
      grade cancer. Using a 6% risk of high-grade cancer as an illustrative cutoff, for
      1000 biopsied men with PSA levels of 3.0ng/mL or higher, the model would reduce
      the need for biopsy in 428 men, detect 119 high-grade cancers, and delay
      diagnosis of 14 of 133 high-grade cancers. Models exhibited excellent
      discrimination on independent validation among men with only serum samples
      available for analysis. CONCLUSIONS: A statistical model based on kallikrein
      markers was validated in a large prospective study and reduces unnecessary
      biopsies while delaying diagnosis of high-grade cancers in few men.

PMID- 25863336
TI  - Unexpected diversity and new species in the sponge-Parazoanthidae association in
      southern Japan.
AB  - Currently the genera Parazoanthus (family Parazoanthidae) and Epizoanthus (family
      Epizoanthidae) are the only sponge-associated zoantharians (Cnidaria, Anthozoa).
      The Parazoanthidae-sponge associations are widely distributed in tropical and
      subtropical waters from the intertidal to the deep sea in the Atlantic and Indo
      Pacific Oceans. However, the taxonomic identification of both parties is often
      confused due to variable morphology and wide ecological ranges. In particular,
      Parazoanthidae species diversity remains poorly understood in the Indo-Pacific.
      In the present study, the diversity of the sponge-zoanthid association in the
      Indo-Pacific was investigated with 71 Parazoanthidae specimens collected from 29
      different locations in Japan (n=22), Australia (n=6) and Florida, USA (n=1). For
      all specimens morphological analyses were performed and total DNA was extracted
      and amplified for four DNA markers (COI-mtDNA, mt 16S-rDNA, ITS-rDNA and ALG11
      nuDNA). The combined data demonstrate that the specimens of this study are
      clearly different from those of all described Parazoanthus species, and lead us
      to erect Umimayanthus gen. n., within family Parazoanthidae, containing the three
      newly described species U. chanpuru sp. n., U. miyabi sp. n., U. nakama sp. n.
      The new genus also includes the previously described species U. parasiticus
      (Duchassaing and Michelotti, 1860; comb. nov.), previously belonging to the genus
      Parazoanthus. Neighbor joining, maximum likelihood and Bayesian posterior
      probability phylogenetic trees clearly demonstrate the monophyly of Umimayanthus
      gen. n. to the exclusion of all outgroup sequences. The phylogenetic results were
      also compared to morphological features, and polyp sizes, amount of sand content
      in tissues, types of connections between polyps, and cnidae data, in particular
      holotrichs-1, were useful in distinguishing the different species within this new
      genus. This new genus can be distinguished from all other Zoantharia by a unique
      and conserved 9 bp insertion and a 14 bp deletion in the mt 16S-rDNA region.
      Additionally, compared to Parazoanthus sensu stricto (i.e. P. axinellae [Schmidt,
      1862]), Umimayanthus spp. are only found associated to sponges, and have a
      coenenchyme much less developed than Parazoanthus sensu stricto. Each new species
      can be distinguished from other congeners by a unique DNA sequence, numbers of
      tentacle, maximum sizes of holotrichs, associated sponge morphology, and colony
      morphology. The identification of the host sponge species is the next logical
      step in this research as this may also aid in the distinction of Umimayanthus
      species.

PMID- 25863335
TI  - A decision support framework for genomically informed investigational cancer
      therapy.
AB  - Rapidly improving understanding of molecular oncology, emerging novel
      therapeutics, and increasingly available and affordable next-generation
      sequencing have created an opportunity for delivering genomically informed
      personalized cancer therapy. However, to implement genomically informed therapy
      requires that a clinician interpret the patient's molecular profile, including
      molecular characterization of the tumor and the patient's germline DNA. In this
      Commentary, we review existing data and tools for precision oncology and present
      a framework for reviewing the available biomedical literature on therapeutic
      implications of genomic alterations. Genomic alterations, including mutations,
      insertions/deletions, fusions, and copy number changes, need to be curated in
      terms of the likelihood that they alter the function of a "cancer gene" at the
      level of a specific variant in order to discriminate so-called "drivers" from
      "passengers." Alterations that are targetable either directly or indirectly with
      approved or investigational therapies are potentially "actionable." At this time,
      evidence linking predictive biomarkers to therapies is strong for only a few
      genomic markers in the context of specific cancer types. For these genomic
      alterations in other diseases and for other genomic alterations, the clinical
      data are either absent or insufficient to support routine clinical implementation
      of biomarker-based therapy. However, there is great interest in optimally
      matching patients to early-phase clinical trials. Thus, we need accessible,
      comprehensive, and frequently updated knowledge bases that describe genomic
      changes and their clinical implications, as well as continued education of
      clinicians and patients.

PMID- 25863337
TI  - Rapid detection of Listeria monocytogenes in milk using confocal micro-Raman
      spectroscopy and chemometric analysis.
AB  - Listeria monocytogenes is a facultatively anaerobic, Gram-positive, rod-shape
      foodborne bacterium causing invasive infection, listeriosis, in susceptible
      populations. Rapid and high-throughput detection of this pathogen in dairy
      products is critical as milk and other dairy products have been implicated as
      food vehicles in several outbreaks. Here we evaluated confocal micro-Raman
      spectroscopy (785 nm laser) coupled with chemometric analysis to distinguish six
      closely related Listeria species, including L. monocytogenes, in both liquid
      media and milk. Raman spectra of different Listeria species and other bacteria
      (i.e., Staphylococcus aureus, Salmonella enterica and Escherichia coli) were
      collected to create two independent databases for detection in media and milk,
      respectively. Unsupervised chemometric models including principal component
      analysis and hierarchical cluster analysis were applied to differentiate L.
      monocytogenes from Listeria and other bacteria. To further evaluate the
      performance and reliability of unsupervised chemometric analyses, supervised
      chemometrics were performed, including two discriminant analyses (DA) and soft
      independent modeling of class analogies (SIMCA). By analyzing Raman spectra via
      two DA-based chemometric models, average identification accuracies of 97.78% and
      98.33% for L. monocytogenes in media, and 95.28% and 96.11% in milk were
      obtained, respectively. SIMCA analysis also resulted in satisfied average
      classification accuracies (over 93% in both media and milk). This Raman
      spectroscopic-based detection of L. monocytogenes in media and milk can be
      finished within a few hours and requires no extensive sample preparation.

PMID- 25863338
TI  - Effect of food processing organic matter on photocatalytic bactericidal activity
      of titanium dioxide (TiO2).
AB  - The purpose of this study was to determine the effect of food processing organic
      matter on photocatalytic bactericidal activity of titanium dioxide (TiO2)
      nanoparticles (NPs). Produce and meat processing wash solutions were prepared
      using romaine lettuce and ground beef samples. Physico-chemical properties such
      as pH, turbidity, chemical oxygen demand (COD), total phenolics (for produce) and
      protein (for meat) content of the extracts were determined using standard
      procedures. The photocatalytic bactericidal activity of TiO2 (1 mg/mL) in
      suspension with or without organic matter against Escherichia coli O157:H7 (5
      strain) was determined over a period of 3h. Increasing the concentration of
      organic matter (either produce or meat) from 0% to 100% resulted in 85% decrease
      in TiO2 microbicidal efficacy. 'Turbidity, total phenolics, and protein contents
      in wash solutions had significant effect on the log reduction. Increasing the
      total phenolics content in produce washes from 20 to 114 mg/L decreased the log
      reduction from 2.7 to 0.38 CFU/mL, whereas increasing the protein content in meat
      washes from 0.12 to 1.61 mg/L decreased the log reduction from and 5.74 to 0.87
      CFU/mL. Also, a linear correlation was observed between COD and total phenolics
      as well as COD and protein contents. While classical disinfection kinetic models
      failed to predict, an empirical equation in the form of "Y=me(nX)" (where Y is
      log reduction, X is COD, and m and n are reaction rate constants) predicted the
      disinfection kinetics of TiO2 in the presence of organic matter (R(2)=94.4). This
      study successfully identified an empirical model with COD as a predictor variable
      to predict the bactericidal efficacy of TiO2 when used in food processing
      environment.

PMID- 25863339
TI  - A strategy to establish Food Safety Model Repositories.
AB  - Transferring the knowledge of predictive microbiology into real world food
      manufacturing applications is still a major challenge for the whole food safety
      modelling community. To facilitate this process, a strategy for creating open,
      community driven and web-based predictive microbial model repositories is
      proposed. These collaborative model resources could significantly improve the
      transfer of knowledge from research into commercial and governmental applications
      and also increase efficiency, transparency and usability of predictive models. To
      demonstrate the feasibility, predictive models of Salmonella in beef previously
      published in the scientific literature were re-implemented using an open source
      software tool called PMM-Lab. The models were made publicly available in a Food
      Safety Model Repository within the OpenML for Predictive Modelling in Food
      community project. Three different approaches were used to create new models in
      the model repositories: (1) all information relevant for model re-implementation
      is available in a scientific publication, (2) model parameters can be imported
      from tabular parameter collections and (3) models have to be generated from
      experimental data or primary model parameters. All three approaches were
      demonstrated in the paper. The sample Food Safety Model Repository is available
      via: http://sourceforge.net/projects/microbialmodelingexchange/files/models and
      the PMM-Lab software can be downloaded from
      http://sourceforge.net/projects/pmmlab/. This work also illustrates that a
      standardized information exchange format for predictive microbial models, as the
      key component of this strategy, could be established by adoption of resources
      from the Systems Biology domain. 

PMID- 25863340
TI  - Antifungal modes of action of Saccharomyces and other biocontrol yeasts against
      fungi isolated from sour and grey rots.
AB  - The aim of this study was to determine the putative modes of action of 59
      viticultural yeasts (31 Saccharomyces and 28 non-Saccharomyces) that inhibited
      fungi isolated from sour and grey rot in grapes. Inhibition of fungal mycelial
      growth by metabolites, enzyme activities (laminarinases, chitinases), antifungal
      volatiles, competition for nutrients (siderophores, Niche Overlap Index (NOI)),
      inhibition of fungal spore germination and decreased germinal tube length and
      induction of resistance were assayed. Biofungicide yeasts were classified into
      "antifungal patterns", according to their mechanisms of action. Thirty isolates
      presented at least two of the mechanisms assayed. We propose that inhibition of
      fungal mycelial growth by metabolites, laminarinases, competition for nutrients,
      inhibition of fungal spore germination and decreased germinal tube length, and
      antifungal volatiles by Saccharomyces and non-Saccharomyces viticultural yeasts
      is used as putative biocontrol mechanisms against phytopathogenic fungi. Twenty
      four different antifungal patterns were identified. Siderophore production (N)and
      a combination of siderophore production and NOI>0.92 (M)were the most frequent
      antifungal patterns observed in the biofungicide yeasts assayed. Elucidation of
      these mechanisms could be useful for optimization of an inoculum formulation,
      resulting in a more consistent control of grey and sour rot with Saccharomyces
      and non-Saccharomyces biocontrol yeasts. 

PMID- 25863342
TI  - A novel and simple cell-based electrochemical impedance biosensor for evaluating
      the combined toxicity of DON and ZEN.
AB  - In this study, a novel and simple cell-based electrochemical biosensor was
      developed to assess the individual and combined toxicity of deoxynivalenol (DON)
      and zearalenone (ZEN) on BEL-7402 cells. The sensor was fabricated by
      modification with AuNPs, p-aminothiophenol, and folic acid in succession. The BEL
      7402 cells which had a good activity were adhered on the electrode through the
      high affinity between the folate receptor and folic acid selectivity. We used the
      collagen to maintain the cell adhesion and viability. Electrochemical impedance
      spectroscopy (EIS) was developed to evaluate the individual and combined toxicity
      of DON and ZEN. Our results indicate that DON and ZEN caused a marked decrease in
      the cell viability in a dose-dependent manner. The value of electrochemical
      impedance spectroscopy decreased with the concentration of DON and ZEN in range
      of 0.1-20, 0.1-50 MUg/ml with the detection limit as 0.03, 0.05 MUg/ml,
      respectively, the IC50 for DON and ZEN as obtained by the proposed
      electrochemical method were 7.1 MUg/ml and 24.6 MUg/ml, respectively, and the
      combination of two mycotoxins appears to generate an additive response. The
      electrochemical cytotoxicity evaluation result was confirmed by biological
      assays. Compared to conventional methods, this electrochemical test is
      inexpensive, highly sensitive, and fast to respond, with long-term monitoring and
      real-time measurements. The proposed method provides a new avenue for evaluating
      the toxicity of mycotoxins.

PMID- 25863341
TI  - The lure of zebrafish in liver research: regulation of hepatic growth in
      development and regeneration.
AB  - The liver is an essential organ that plays a pivotal role in metabolism,
      digestion and nutrient storage. Major efforts have been made to develop zebrafish
      (Danio rerio) as a model system to study the pathways regulating hepatic growth
      during liver development and regeneration. Zebrafish offer unique advantages over
      other vertebrates including in vivo imaging at cellular resolution and the
      capacity for large-scale chemical and genetic screens. Here, we review the
      cellular and molecular mechanisms that regulate hepatic growth during liver
      development in zebrafish. We also highlight emerging evidence that developmental
      pathways are reactivated following liver injury to facilitate regeneration.
      Finally, we discuss how zebrafish have transformed drug discovery efforts and
      enabled the identification of drugs that stimulate hepatic growth and provide
      hepatoprotection in pre-clinical models of liver injury, with the ultimate goal
      of identifying novel therapeutic approaches to treat liver disease. 

PMID- 25863343
TI  - A glucose oxidase-coupled DNAzyme sensor for glucose detection in tears and
      saliva.
AB  - Biosensors have been widely investigated and utilized in a variety of fields
      ranging from environmental monitoring to clinical diagnostics. Glucose biosensors
      have triggered great interest and have been widely exploited since glucose
      determination is essential for diabetes diagnosis. In here, we designed a novel
      dual-enzyme biosensor composed of glucose oxidase (GOx) and pistol-like DNAzyme
      (PLDz) to detect glucose levels in tears and saliva. First, GOx, as a molecular
      recognition element, catalyzes the oxidation of glucose forming H2O2; then PLDz
      recognizes the produced H2O2 as a secondary signal and performs a self-cleavage
      reaction promoted by Mn(2+), Co(2+) and Cu(2+). Thus, detection of glucose could
      be realized by monitoring the cleavage rate of PLDz. The slope of the cleavage
      rate of PLDz versus glucose concentration curve was fitted with a Double
      Boltzmann equation, with a range of glucose from 100 nM to 10mM and a detection
      limit of 5 MUM. We further applied the GOx-PLDz 1.0 biosensor for glucose
      detection in tears and saliva, glucose levels in which are 720+/-81 MUM and 405+/
      56 MUM respectively. Therefore, the GOx-PLDz 1.0 biosensor is able to determine
      glucose levels in tears and saliva as a noninvasive glucose biosensor, which is
      important for diabetic patients with frequent/continuous glucose monitoring
      requirements. In addition, induction of DNAzyme provides a new approach in the
      development of glucose biosensors.

PMID- 25863344
TI  - Yeast dual-affinity biobricks: Progress towards renewable whole-cell biosensors.
AB  - Point-of-care (POC) diagnostic biosensors offer a promising solution to improve
      healthcare, not only in developed parts of the world, but also in resource
      limited areas that lack adequate medical infrastructure and trained technicians.
      However, in remote and resource limited settings, cost and storage of traditional
      POC immunoassays often limit actual deployment. Synthetically engineered
      biological components ("BioBricks") provide an avenue to reduce costs and
      simplify assay procedures. In this article, the design and development of an
      ultra-low cost, whole-cell "renewable" capture reagent for use in POC diagnostic
      applications is described. Yeast cells were genetically modified to display both
      single chain variable fragment (scFv) antibodies and gold-binding peptide (GBP)
      on their surfaces for simple one step enrichment and surface functionalization.
      Electrochemical impedance spectroscopy (EIS) and fluorescent imaging were used to
      verify and characterize the binding of cells to gold electrodes. A complete
      electrochemical detection assay was then performed on screen-printed electrodes
      fixed with yeast displaying scFv directed to Salmonella outer membrane protein D
      (OmpD). Electrochemical assays were optimized and cross-validated with
      established fluorescence techniques. Nanomolar detection limits were observed for
      both formats. 

PMID- 25863345
TI  - Structural insight into the mechanism of amyloid precursor protein recognition by
      beta-secretase 1: A molecular dynamics study.
AB  - beta-secretase 1 (BACE1) initiates the proteolysis of amyloid precursor protein
      (APP) to generate Abeta, aggregation of which has been considered to be the main
      histopathological feature of Alzheimer's Disease. Here, we have explored the
      conformational switching of BACE1 during APP recognition using molecular dynamics
      simulation thereby suggesting the recognition to be a conformational selection
      process. Free BACE1 is highly flexible and exists as an ensemble of
      conformations. The beta-hairpin flap that covers the active site of BACE1 visits
      numerous conformations during the simulation. Essential dynamics reveal that
      concerted movements in several loops including the flap region lead to a
      conformational switching from open to closed form. During the simulation, free
      BACE1 visits both the open and closed forms multiple times. Binding of APP to the
      BACE1 cavity shifts the equilibrium towards a stable complex stabilized by strong
      electrostatic surface complementarity along with several van der Waals and
      hydrogen bonding interactions. 

PMID- 25863346
TI  - Modulation of the steroidogenic related activity according to the design of
      single-chain bovine FSH analogs.
AB  - Single-chain (SC) gonadotropins have been genetically engineered to increase the
      repertoire of analogs for potential use in humans and domestic animals. The major
      aim of the current study was to examine the steroidogenic related activity of SC
      FSH analogs carrying structural differences. To address this issue, we designed
      and expressed three SC bovine FSH analogs in CHO cells: (i) FSHbetaalpha in which
      the tethered subunit domains are linked in tandem; (ii) FSHbetaCTPalpha that
      contains the carboxy terminal peptide (CTP) of the human choriogonadotropin (hCG)
      beta subunit as a spacer, and (iii) FSHbetaboCTPalpha in which the linker is
      derived from a CTP-like sequence (boCTP) decoded from the bovine LHbeta DNA. The
      data suggested that the secretion efficiency of these variants from the
      transfected cells was unaffected by the presence or absence of the CTP linker, N
      glycans were attached to the analogs and the hCGbeta-CTP domain in the
      FSHbetaCTPalpha variant was O-glycosylated. In a rat immortalized granulosa cell
      bioassay the potency of the three variants towards progesterone secretion varied.
      In immature mice, the analogs increased the ovary weight and induced StAR, Cyp11a
      (P450scc), Cyp17 (P450c17) and Cyp19 (P450aromatase) transcripts. However, the
      dose dependence and amplitude of these transcript levels differed in response to
      FSHbetaalpha, FSHbetaboCTPalpha and FSHbetaCTPalpha. Collectively, these data
      suggest that the design of the FSH analog can modulate the bioactivity in vitro
      and in vivo. A systematic analysis of receptor activation with ligands carrying
      structural differences may identify new regulatory factor/s involved in the
      pleiotropic FSH activity. 

PMID- 25863347
TI  - Characterization of little skate (Leucoraja erinacea) recombinant transthyretin:
      Zinc-dependent 3,3',5-triiodo-l-thyronine binding.
AB  - Transthyretin (TTR) diverged from an ancestral 5-hydroxyisourate hydrolase
      (HIUHase) by gene duplication at some early stage of chordate evolution. To
      clarify how TTR had participated in the thyroid system as an extracellular
      thyroid hormone (TH) binding protein, TH binding properties of recombinant little
      skate Leucoraja erinacea TTR was investigated. At the amino acid level, skate TTR
      showed 37-46% identities with the other vertebrate TTRs. Because the skate TTR
      had a unique histidine-rich segment in the N-terminal region, it could be
      purified by Ni-affinity chromatography. The skate TTR was a 46-kDa homotetramer
      of 14.5kDa subunits, and had one order of magnitude higher affinity for 3,3',5
      triiodo-l-thyronine (T3) and some halogenated phenols than for l-thyroxine.
      However, the skate TTR had no HIUHase activity. Ethylenediaminetetraacetic acid
      (EDTA) treatment inhibited [(125)I]T3 binding activity whereas the addition of
      Zn(2+) to the EDTA-treated TTR recovered [(125)I]T3 binding activity in a Zn(2+)
      concentration-dependent manner. Scatchard analysis revealed the presence of two
      classes of binding site for T3, with dissociation constants of 0.24 and 17nM.
      However, the high-affinity sites were completely abolished with 1mM EDTA, whereas
      the remaining low-affinity sites decreased binding capacity. The number of zinc
      per TTR was quantified to be 4.5-6.3. Our results suggest that skate TTR has
      tight Zn(2+)-binding sites, which are essential for T3 binding to at least the
      high-affinity sites. Zn(2+) binding to the N-terminal histidine-rich segment may
      play an important role in acquisition or reinforcement of TH binding ability
      during early evolution of TTR. 

PMID- 25863348
TI  - Differential expression of three estrogen receptors mRNAs in tissues, growth
      development, embryogenesis and gametogenesis from large yellow croaker,
      Larimichthys crocea.
AB  - The biological activity of estrogens in target organs is mainly mediated by
      estrogen receptors (ERs). Herein, we addressed the isolation and expression
      analysis of three nuclear estrogen receptors, namely LcERalpha, LcERbeta1, and
      LcERbeta2 from Larimichthys crocea by means of SMART-RACE, qRT-PCR, and in situ
      hybridization. Results in different tissues showed that both LcERalpha and
      LcERbeta2 had the highest expression levels in female liver, followed by testis,
      but LcERbeta1 expression level was significantly higher in testis and ovary than
      in other tissues. Expression of LcERalpha and LcERbeta2 was significantly higher
      than LcERbeta1 in female liver, and LcERbeta2 was significantly higher than
      LcERalpha and LcERbeta1 in male liver. Moreover, we analyzed the expression of
      LcERs in gonad and liver at three different growth stages during the same
      breeding season. Significant up-regulated expression of LcERalpha and LcERbeta2
      were found in female liver at 1000dph compared with at 270dph. The expression of
      LcERbeta2 was prominently higher in male liver than LcERalpha, LcERbeta1 and
      LcAR, while LcERbeta1 was lower than other receptors in male and female liver at
      all the three stages. In ovary, LcERalpha at 270dph was lower than at 635dph and
      1000dph, but had no significant change in testis. The two LcERbeta subtypes and
      LcAR highly expressed in the early testis, and gradually decrease with the
      development of testis. In embryogenesis, a significant increase in the expression
      of LcERalpha and LcERbeta2 were observed after appearance of optic vesicles phase
      (11.8hpf). LcERbeta1 gradually decrease with the embryogenesis but increased
      dramatically at 1dph. Results of in situ hybridization showed that signals of
      LcERalpha and LcERbeta1 mRNA were mainly detected in Stage I-Stage IV oocytes, as
      well as in follicle cells around the Stage II-Stage IV and degenerated oocytes.
      Signals of LcERbeta2 were detected in the cytoplasm of Stage I and Stage II
      oocytes but not in the follicle cells of all oocytes stages. In parallel,
      LcERalpha and LcERbeta1 were detected in all cell types of spermatogenesis, but
      in terms of LcERbeta2, little or no signals were detected during spermatogenesis.
      Based on these results, we deduced that both LcERalpha and LcERbeta2 play a major
      role in mediating the physiological effects of estrogen in female liver, and
      LcERbeta2 maybe also play an important role in regulation of vitellogenesis in
      male liver. Differential expression of LcERs and LcAR imply their physiological
      functions during development and differentiation of gonad. The signals for
      LcERalpha and LcERbeta1 in follicle cells suggested that the follicle cell maybe
      an important site of estrogen action, by which estrogens exert influences on the
      maturation oocytes and ovulation. Furthermore, the steroid hormones produced by
      follicle cells may be related to the differential distributions among ER
      subtypes. Besides, we deduced that LcERalpha and LcERbeta1 rather than LcERbeta2
      may play a major role in spermatogenesis of croaker. However, the differential
      expression of LcERbeta2 during gametogenesis also implicates its certain
      functions in mediating physiological process of estrogen action. 

PMID- 25863349
TI  - Effects of insulin-like growth factor-1 on the assembly and secretion of very low
      density lipoproteins in cow hepatocytes in vitro.
AB  - Fatty liver is a major metabolic disorder of dairy cows. One important reason is
      that hepatic very low-density lipoproteins (VLDL) assembly was significant
      decreased in dairy cows with fatty liver. In addition, the impairment of insulin
      like growth factor (IGF)-1 synthesis was involved in the development of fatty
      liver. Therefore, the objective of this study was to investigate the effects of
      IGF-1 on the VLDL assembly in cow hepatocytes. In this study, cow hepatocytes
      were cultured and then transfected with Ad-GFP-IGF-1 (inhibited the IGF-1
      expression) and Ad-GFP (negative control), and treated with different
      concentrations of IGF-1, respectively. The results showed that IGF-1 increased
      the mRNA abundance of apolipoprotein B100 (ApoB100), apolipoprotein E (ApoE),
      microsomal triglyceride transfer protein (MTTP), and low-density lipoprotein
      receptor (LDLR) and then increased the VLDL assembly in cow hepatocytes.
      Nevertheless, impairment of IGF-1 expression by Ad-GFP-IGF-1 could inhibit above
      genes expression and VLDL assembly in hepatocytes. Taken together, these results
      indicate that IGF-1 increases the VLDL assembly and impairment of IGF-1
      expression decreases the VLDL assembly in cow hepatocytes. 

PMID- 25863350
TI  - Neuroprotective effects of a polyphenolic white grape juice extract in a mouse
      model of experimental autoimmune encephalomyelitis.
AB  - In the last 20 years, wine phenolic compounds have received increasing interest
      since several epidemiological studies have suggested associations between regular
      consumption of moderate amount of wine and prevention of certain chronic
      pathologies, such as neurodegenerative diseases. This study was aimed to
      investigate the possible neuroprotective role of a polyphenolic white grape juice
      extract (WGJe) in an experimental mice model of autoimmune encephalomyelitis
      (EAE), the most commonly used model for multiple sclerosis (MS) in vivo. EAE
      mimics the main features of MS, including paralysis, weight loss, demyelination,
      central nervous system (CNS) inflammation and blood-brain barrier (BBB)
      breakdown. Our study demonstrated that oral administration of WGJe (20 and 40
      mg/kg/day) may exert neuroprotective effects against MS, diminishing both
      clinical signs and histological score typical of disease (lymphocytic
      infiltration and demyelination). In particular, by western blot, histological
      evaluations and immunolocalization of the main markers of inflammation, oxidative
      stress and apoptosis (TNF-alpha, iNOS, Nitrotyrosine, PARP, Foxp3, Bcl-2, Caspase
      3 and DNA fragmentation), we documented that WGJe counteracts the alteration of
      all these inflammatory and oxidative pathway, without any apparent sign of
      toxicity. On these bases, we propose this natural product as putative novel
      helpful tools for the prevention of autoimmune and neurodegenerative diseases
      such as MS. WGJe could have considerable implication for future therapies of MS,
      and this study may represents the starting point for further investigation on the
      role of WGJe in neuroinflammation.

PMID- 25863351
TI  - Isoquinoline alkaloids as prolyl oligopeptidase inhibitors.
AB  - Prolyl oligopeptidase is a cytosolic serine peptidase that hydrolyses proline
      containing peptides at the carboxy terminus of proline residues. It has been
      associated with schizophrenia, bipolar affective disorder, and related
      neuropsychiatric disorders and therefore may have important clinical
      implications. Thirty-one isoquinoline alkaloids of various structural types,
      previously isolated in our laboratory, were screened for their ability to inhibit
      prolyl oligopeptidase. Promising results have been showed by alkaloids
      californidine (IC50=55.6+/-3.5 MUM), dihydrosanquinarine (IC50=99.1+/-7.6 MUM),
      corypalmine (IC50=128.0+/-10.5 MUM) and N-methyllaurotetanine (IC50=135.0+/-11.7
      MUM).

PMID- 25863352
TI  - Clathrin-dependent endocytosis plays a predominant role in cellular uptake of
      double-stranded RNA in the red flour beetle.
AB  - RNA interference (RNAi) is a highly conserved gene regulatory mechanism in
      eukaryotic organisms; however, an understanding of mechanisms of cellular uptake
      of double-stranded RNA (dsRNA) in different organisms remains elusive. By using
      pharmacological inhibitors of different endocytic pathways in conjunction with
      RNAi of a marker gene (lethal giant larvae, TcLgl) in the red flour beetle
      (Tribolium castaneum), we demonstrated that two inhibitors (chlorpromazine and
      bafilomycin-A1) of clathrin-dependent endocytosis can nearly abolish or
      significantly diminish RNAi of TcLgl, whereas methyl-beta-cyclodextrin and
      cytochalasin-D, known to inhibit other endocytic pathways, showed no effect on
      RNAi of TcLgl. By using Cy3-labeled TcLgl dsRNA, we observed significantly
      reduced cellular uptake of TcLgl dsRNA in midgut cells after larvae were injected
      with each of the two clathrin-dependent endocytosis inhibitors. By using an "RNAi
      of RNAi" strategy, we further demonstrated that suppression of each transcript of
      the four key genes encoding clathrin heavy chain (TcChc), clathrin coat assembly
      protein AP50 (TcAP50), vacuolar (H(+))-ATPase subunit H (TcVhaSFD) and a ras
      related protein (TcRab7) in clathrin-dependent endocytosis by RNAi can
      significantly impair RNAi of TcLgl. These results support our conclusion that
      clathrin-dependent endocytosis is a major mechanism in cellular uptake of dsRNA
      in T. castaneum. Our study also provides new insights into improving RNAi
      efficiency by enhancing dsRNA endosomal release. 

PMID- 25863353
TI  - Copper-zinc coergisms and metal toxicity at predefined ratio concentrations:
      Predictions based on synergistic ratio model.
AB  - A significant number of studies have centred on the single actions of heavy
      metals against test animals in predicting aquatic toxicity. However, practical
      existence of environmental toxicants is in multiple mixtures and variable
      undefined ratio combinatorial concentrations. Pollution abatement approaches in
      setting representative safe boundaries for metal contaminants is crucial with
      factual data on predictively modelled exposures of organisms to multiple
      mixtures. In continuance of our approach to toxicity of individual heavy metals,
      we determined the toxicity of binary mixtures of copper and zinc at predetermined
      ratios against tilapia species and also evaluated the coergisms based on
      synergistic ratio model for effective formulations of safe limits. Orecohromis
      niloticus species were exposed to copper and zinc (Cu:Zn) at ratios of 1:1 and
      1:2 on 96hLC50 index and mortality response analysed following the probit-log
      dose regression with metal-metal interactions effectively modelled. The 96hLC50
      values for Cu:Zn were calculated to be 68.898 and 51.197 mg/l for ratios 1:1 and
      1:2, respectively. The joint action toxicity of the metal mixtures was observed
      to differ from the metals acting singly against the same animal species.
      Synergistic coergisms were realized in most of the ratio mixtures except the
      antagonistic effect displayed by the combination of Cu:Zn in the ratio 1:1 when
      compared to the single action of copper. Biological toxicity of heavy metals
      however still appears uncertain, and consideration of multiple mixtures and
      interactions of toxicants in natural milieu is very crucial in environmental
      management of the existing and emerging contaminating metals.

PMID- 25863354
TI  - Detection and location of OP-degrading activity: A model to integrate education
      and research.
AB  - The Environmental Sampling Research Module (ESRM) is an investigative/discovery
      module that provides undergraduate research experiences for students as part of
      an interdisciplinary research-based biotechnology curriculum at the University of
      Houston campus. As part of the ESRM, students collect soil samples from various
      locations to test for the presence of organophosphorous (OP) degrading bacteria.
      At the end of this research project students submit a research paper on their
      field and laboratory activities and discuss their experimental data and
      observations. Students also record the date, location of collection, and the
      results of testing the sample for the degradation of two pesticides, methyl
      parathion or paraoxon, in an electronic laboratory notebook (ELN). Each
      collection site is recorded on a Google Maps module and the data from student
      research activities is made available to other undergraduate students. This data
      is then used to generate a microorganism database of pesticide degrading activity
      and promote reading, critical thinking, and analytical skills as part of the
      curriculum. Our sampling of agricultural sites and wastewater within and around
      the city of Houston has identified seven distinct genera of OP degrading
      organisms, including Pseudomonas, Stenotrophomonas, Exiguobacterium, Delftia,
      Agrobacterium, Aeromonas, and Rhizobium. Collected strains exhibit
      phosphotriesterase-like enzymatic activity with isolates of Pseudomonas putida
      and Stenotrophomonas maltophilia capable of degrading both the phosphotriester
      paraoxon and the phosphorothioate methyl parathion. Using this collection of OP
      degrading microorganisms, undergraduate students have evaluated their potential
      for enhancing the removal of harmful organophosphates and their toxic metabolites
      from contaminated agricultural soil and adjacent bodies of water. This analytical
      data can potentially be utilized for environmental and industrial applications in
      bioremediation and ecology providing an innovative method for integrating
      education and research. In addition, the versatility of the ESRM itself provides
      for easy and rapid adaptation into varying environmental science courses with
      significant potential for the discovery and isolation of new and unique organisms
      to be used as part of ongoing research in the laboratory. 

PMID- 25863356
TI  - Medicinal plants in the treatment of women's disorders: Analytical strategies to
      assure quality, safety and efficacy.
AB  - During last decades an increasing number of herbal products specifically
      targeting women's disorders has appeared in the worldwide marketplace. This
      growth highlights the need for a critical evaluation of quality, safety and
      efficacy of these products. Analytical techniques applied to the quality control
      of the main medicinal plants used for women health (relief of menopause and
      menstrual related symptoms) have been reviewed. Thanks to the innovation in
      analytical technology, identification and detection of secondary metabolites
      dramatically improved. In particular, hyphenated techniques have proved to be the
      most suitable for the rapid identification of compounds in plant matrix.
      Moreover, taking into account that differences in sample quality are not only
      found in the main compounds or in the chemical markers but also in the low
      concentration compounds, fingerprint analysis might be a simple way for
      identification and quality control of herbal products containing a large number
      of low amounts of unknown compounds. Furthermore in several papers the
      informations obtained from the analysis of a plant have been processed by
      statistical elaborations. Medicinal plants here discussed are classified on the
      basis of the chemical markers used for their quality control. 

PMID- 25863355
TI  - Evidence for early neurodegeneration in the cervical cord of patients with
      primary progressive multiple sclerosis.
AB  - Spinal neurodegeneration is an important determinant of disability progression in
      patients with primary progressive multiple sclerosis. Advanced imaging
      techniques, such as single-voxel (1)H-magnetic resonance spectroscopy and q-space
      imaging, have increased pathological specificity for neurodegeneration, but are
      challenging to implement in the spinal cord and have yet to be applied in early
      primary progressive multiple sclerosis. By combining these imaging techniques
      with new clinical measures, which reflect spinal cord pathology more closely than
      conventional clinical tests, we explored the potential for spinal magnetic
      resonance spectroscopy and q-space imaging to detect early spinal
      neurodegeneration that may be responsible for clinical disability. Data from 21
      patients with primary progressive multiple sclerosis within 6 years of disease
      onset, and 24 control subjects were analysed. Patients were clinically assessed
      on grip strength, vibration perception thresholds and postural stability, in
      addition to the Expanded Disability Status Scale, Nine Hole Peg Test, Timed 25
      Foot Walk Test, Multiple Sclerosis Walking Scale-12, and Modified Ashworth Scale.
      All subjects underwent magnetic resonance spectroscopy and q-space imaging of the
      cervical cord and conventional brain and spinal magnetic resonance imaging at 3
      T. Multivariate analyses and multiple regression models were used to assess the
      differences in imaging measures between groups and the relationship between
      magnetic resonance imaging measures and clinical scores, correcting for age,
      gender, spinal cord cross-sectional area, brain T2 lesion volume, and brain white
      matter and grey matter volume fractions. Although patients did not show
      significant cord atrophy when compared with healthy controls, they had
      significantly lower total N-acetyl-aspartate (mean 4.01 versus 5.31 mmol/l, P =
      0.020) and glutamate-glutamine (mean 4.65 versus 5.93 mmol/l, P = 0.043) than
      controls. Patients showed an increase in q-space imaging-derived indices of
      perpendicular diffusivity in both the whole cord and major columns compared with
      controls (P < 0.05 for all indices). Lower total N-acetyl-aspartate was
      associated with higher disability, as assessed by the Expanded Disability Status
      Scale (coefficient = -0.41, 0.01 < P < 0.05), Modified Ashworth Scale
      (coefficient = -3.78, 0.01 < P < 0.05), vibration perception thresholds
      (coefficient = -4.37, P = 0.021) and postural sway (P < 0.001). Lower glutamate
      glutamine predicted increased postural sway (P = 0.017). Increased perpendicular
      diffusivity in the whole cord and columns was associated with increased scores on
      the Modified Ashworth Scale, vibration perception thresholds and postural sway (P
      < 0.05 in all cases). These imaging findings indicate reduced structural
      integrity of neurons, demyelination, and abnormalities in the glutamatergic
      pathways in the cervical cord of early primary progressive multiple sclerosis, in
      the absence of extensive spinal cord atrophy. The observed relationship between
      imaging measures and disability suggests that early spinal neurodegeneration may
      underlie clinical impairment, and should be targeted in future clinical trials
      with neuroprotective agents to prevent the development of progressive disability.

PMID- 25863357
TI  - Inhibition of 14-3-3 Proteins Leads to Schizophrenia-Related Behavioral
      Phenotypes and Synaptic Defects in Mice.
AB  - BACKGROUND: The 14-3-3 family of proteins is implicated in the regulation of
      several key neuronal processes. Previous human and animal studies suggested an
      association between 14-3-3 dysregulation and schizophrenia. METHODS: We
      characterized behavioral and functional changes in transgenic mice that express
      an isoform-independent 14-3-3 inhibitor peptide in the brain. RESULTS: We
      recently showed that 14-3-3 functional knockout mice (FKO) exhibit impairments in
      associative learning and memory. We report here that these 14-3-3 FKO mice
      display other behavioral deficits that correspond to the core symptoms of
      schizophrenia. These behavioral deficits may be attributed to alterations in
      multiple neurotransmission systems in the 14-3-3 FKO mice. In particular,
      inhibition of 14-3-3 proteins results in a reduction of dendritic complexity and
      spine density in forebrain excitatory neurons, which may underlie the altered
      synaptic connectivity in the prefrontal cortical synapse of the 14-3-3 FKO mice.
      At the molecular level, this dendritic spine defect may stem from dysregulated
      actin dynamics secondary to a disruption of the 14-3-3-dependent regulation of
      phosphorylated cofilin. CONCLUSIONS: Collectively, our data provide a link
      between 14-3-3 dysfunction, synaptic alterations, and schizophrenia-associated
      behavioral deficits.

PMID- 25863359
TI  - Stress In Utero: Prenatal Programming of Brain Plasticity and Cognition.
AB  - Animal studies confirm earlier anecdotal observations in humans to indicate that
      early life experience has a profound impact on adult behavior, years after the
      original experience has vanished. These studies also highlight the role of early
      life adversaries in the shaping of a disordered brain. Evidence is accumulating
      to indicate that the epigenome, through which the environment regulates gene
      expression, is responsible for long-lasting effects of stress during pregnancy on
      brain and behavior. A possible differential effect of the environment on the
      epigenome may underlie the observation that only a small fraction of a population
      with similar genetic background deteriorates into mental disorders. Considerable
      progress has been made in the untangling of the epigenetic mechanisms that
      regulate emotional brain development. The present review focuses on the lasting
      effects of prenatal stress on brain plasticity and cognitive functions in human
      and rodent models. Although human studies stress the significance of early life
      experience in functional maturation, they lack the rigor inherent in controlled
      animal experiments. Furthermore, the analysis of molecular and cellular
      mechanisms affected by prenatal stress is possible only in experimental animals.
      The present review attempts to link human and animal studies while proposing
      molecular mechanisms that interfere with functional brain development. 

PMID- 25863360
TI  - Attentional Bias Predicts Increased Reward Salience and Risk Taking in Bipolar
      Disorder.
AB  - BACKGROUND: There is amassing evidence that risky decision-making in bipolar
      disorder is related to reward-based differences in frontostriatal regions.
      However, the roles of early attentional and later cognitive processes remain
      unclear, limiting theoretical understanding and development of targeted
      interventions. METHODS: Twenty euthymic bipolar disorder and 19 matched control
      participants played a Roulette task in which they won and lost money. Event
      related potentials and source analysis were used to quantify predominantly
      sensory-attentional (N1), motivational salience (feedback-related negativities
      [FRN]), and cognitive appraisal (P300) stages of processing. We predicted that
      the bipolar disorder group would show increased N1, consistent with increased
      attentional orienting, and reduced FRN, consistent with a bias to perceive
      outcomes more favorably. RESULTS: As predicted, the bipolar disorder group showed
      increased N1 and reduced FRN but no differences in P300. N1 amplitude was
      additionally associated with real-life risk taking, and N1 source activity was
      reduced in visual cortex but increased activity in precuneus, frontopolar, and
      premotor cortex, compared to those of controls. CONCLUSIONS: These findings
      demonstrate an early attentional bias to reward that potentially drives risk
      taking by priming approach behavior and elevating reward salience in the
      frontostriatal pathway. Although later cognitive appraisals of these inputs may
      be relatively intact in remission, interventions targeting attention orienting
      may also be effective in long-term reduction of relapse.

PMID- 25863358
TI  - Alterations in cortical network oscillations and parvalbumin neurons in
      schizophrenia.
AB  - Cognitive deficits are a core clinical feature of schizophrenia but respond
      poorly to available medications. Thus, understanding the neural basis of these
      deficits is crucial for the development of new therapeutic interventions. The
      types of cognitive processes affected in schizophrenia are thought to depend on
      the precisely timed transmission of information in cortical regions via
      synchronous oscillations at gamma band frequency. Here, we review 1) data from
      clinical studies suggesting that induction of frontal cortex gamma oscillations
      during tasks that engage cognitive or complex perceptual functions is attenuated
      in schizophrenia; 2) findings from basic neuroscience studies highlighting the
      features of parvalbumin-positive interneurons that are critical for gamma
      oscillation production; and 3) results from recent postmortem human brain studies
      providing additional molecular bases for parvalbumin-positive interneuron
      alterations in prefrontal cortical circuitry in schizophrenia. 

PMID- 25863361
TI  - The puzzle of processing speed, memory, and executive function impairments in
      schizophrenia: fitting the pieces together.
AB  - BACKGROUND: Substantial impairment in performance on the digit-symbol
      substitution task in patients with schizophrenia is well established, which has
      been widely interpreted as denoting a specific impairment in processing speed.
      However, other higher order cognitive functions might be more critical to
      performance on this task. To date, this idea has not been rigorously investigated
      in patients with schizophrenia. METHODS: Neuropsychological measures of
      processing speed, memory, and executive functioning were completed by 125
      patients with schizophrenia and 272 control subjects. We implemented a series of
      confirmatory factor and structural regression modeling to build an integrated
      model of processing speed, memory, and executive function with which to
      deconstruct the digit-symbol substitution task and characterize discrepancies
      between patients with schizophrenia and control subjects. RESULTS: The overall
      structure of the processing speed, memory, and executive function model was the
      same across groups (chi(2) = 208.86, p > .05), but the contribution of the
      specific cognitive domains to coding task performance differed significantly.
      When completing the task, control subjects relied on executive function and,
      indirectly, on working memory ability, whereas patients with schizophrenia used
      an alternative set of cognitive operations whereby they relied on the same
      processes required to complete verbal fluency tasks. CONCLUSIONS: Successful
      coding task performance relies predominantly on executive function, rather than
      processing speed or memory. Patients with schizophrenia perform poorly on this
      task because of an apparent lack of appropriate executive function input; they
      rely instead on an alternative cognitive pathway.

PMID- 25863362
TI  - Sessile and mobile components of a benthic ecosystem display mixed trends within
      a temperate marine reserve.
AB  - Despite recent efforts to increase the global coverage of marine protected areas
      (MPAs), studies investigating the effectiveness of marine protected areas within
      temperate waters remain scarce. Furthermore, out of the few studies published on
      MPAs in temperate waters, the majority focus on specific ecological or fishery
      components rather than investigating the ecosystem as a whole. This study
      therefore investigated the dynamics of both benthic communities and fish
      populations within a recently established, fully protected marine reserve in
      Lamlash Bay, Isle of Arran, United Kingdom, over a four year period. A
      combination of photo and diver surveys revealed live maerl (Phymatolithon
      calcareum), macroalgae, sponges, hydroids, feather stars and eyelash worms
      (Myxicola infundibulum) to be significantly more abundant within the marine
      reserve than on surrounding fishing grounds. Likewise, the overall composition of
      epifaunal communities in and outside the reserve was significantly different.
      Both results are consistent with the hypothesis that protecting areas from
      fishing can encourage seafloor habitats to recover. In addition, the greater
      abundance of complex habitats within the reserve appeared to providing nursery
      habitat for juvenile cod (Gadus morhua) and scallops (Pecten maximus and
      Aequipecten opercularis). In contrast, there was little difference in the
      abundance of mobile benthic fauna, such as crabs and starfish, between the
      reserve and outside. Similarly, the use of baited underwater video cameras
      revealed no difference in the abundance and size of fish between the reserve and
      outside. Limited recovery of these ecosystem components may be due to the
      relatively small size (2.67 km(2)) and young age of the reserve (<5 years), both
      of which might have limited the extent of any benefits afforded to mobile fauna
      and fish communities. Overall, this study provides evidence that fully protected
      marine reserves can encourage seafloor habitats to recover, which in turn, can
      create a number of benefits that flow back to other species, including those of
      commercial importance.

PMID- 25863363
TI  - Speciation of cisplatin in environmental water samples by hydrophilic interaction
      liquid chromatography coupled to inductively coupled plasma mass spectrometry.
AB  - Cisplatin is still widely used for treatment of numerous types of tumours.
      Different speciation methods have been applied to study behaviour of the intact
      drug and its individual biotransformation species in various clinical samples.
      These methods are mainly based on electrophoresis, size exclusion (SEC) or ion
      chromatography (IC) techniques coupled to inductively coupled plasma mass
      spectrometry (ICP-MS). Hydrophilic interaction liquid chromatography (HILIC),
      which is a common technique for separation of polar substances, was rarely
      applied for separation of cisplatin and its hydrolysed metabolites. There is also
      a lack of information available on the occurrence of cisplatin and its hydrolysed
      complexes in the environmental waters. In the present study the concentrations of
      Pt were determined in hospital wastewaters by ICP-MS. A procedure for separation
      of cisplatin and its aqueous hydrolysed complexes by the use of HILIC column was
      optimized. Quantification of separated Pt species was performed by isotope
      dilution (ID)-ICP-MS procedure. Low limits of detection (LODs) and quantification
      (LOQs) were obtained for cisplatin and its hydrolysed complexes ranging from
      0.0273 to 0.1726 ng Pt/mL and from 0.0909 to 0.5753 ng Pt/mL, respectively. Good
      repeatability of the procedure with relative standard deviation (RSD) lower than
      +/-2.3% was obtained. The column recoveries, which ranged from 95 to 101%,
      indicated that the procedure developed enabled quantitative speciation analysis
      of aqueous cisplatin complexes. The ZIC-HILIC-ID-ICP-MS procedure was
      successfully applied in speciation of cisplatin in spiked hospital wastewater
      samples.

PMID- 25863364
TI  - Methyl oleate as matrix simulacrum for the simultaneous determination of metals
      in biodiesel samples by flame atomic emission spectroscopy.
AB  - A measurement procedure for direct and simultaneous quantification of Na, K and
      Ca in biodiesel by flame atomic emission spectroscopy (FAES) was developed. A lab
      made device was constructed by coupling a nebulizer/combustion system from a
      commercial photometer to a continuous emission detector in a spectral range of
      255 to 862 nm. Instrumental optimizations were carried out evaluating the most
      important variables, such as gas flow rates and sample introduction temperature,
      indicating that a temperature of 50 degrees C enhances the analytical signals and
      assures good precision. The direct analysis method was properly validated and
      presented limits of quantification of 0.09, 0.07 and 0.43 MUg kg(-1) for Na, K
      and Ca, respectively. Accuracy of the proposed procedure was checked by comparing
      the results with those obtained by the standard procedure described in ABNT NBR
      15556 and the standard addition method.

PMID- 25863365
TI  - An enzyme-free and label-free fluorescent biosensor for small molecules by G
      quadruplex based hybridization chain reaction.
AB  - An enzyme-free and label-free fluorescent biosensor is developed by G-quadruplex
      based hybridization chain reaction (HCR) for small molecules, using adenosine
      triphosphate (ATP) as the model. Aptamer probes for the recognition of small
      molecules are hybridized with blocking probes. The G-quadruplex sequences are
      incorporated into one of the two HCR hairpin probes. In the presence of small
      molecules (ATP), the formation of aptamer-ATP bioaffinity complexes induces the
      release of blocking probes; the released blocking probes initiate HCR and
      numerous G-quadruplexes along DNA nanowires are self-assembled after the HCR
      process. Using N-methyl mesoporphyrin IX (NMM) as the fluorophore, a "turn-on"
      fluorescence response can be achieved and detected as low as 15 MUmol L(-1) of
      ATP. This biosensor is applied to detect ATP in biologic samples with
      satisfactory results.

PMID- 25863366
TI  - Detection and quantification of reactive oxygen species (ROS) in indoor air.
AB  - Reactive oxygen species (ROS), such as free radicals and peroxides, are
      environmental trace pollutants potentially associated with asthma and airways
      inflammation. These compounds are often not detected in indoor air due to
      sampling and analytical limitations. This study developed and validated an
      experimental method to sample, identify and quantify ROS in indoor air using
      fluorescent probes. Tests were carried out simultaneously using three different
      probes: 2',7'-dichlorofluorescin (DCFH) to detect a broad range of ROS, Amplex
      ultra Red(r) (AuR) to detect peroxides, and terephthalic acid (TPA) to detect
      hydroxyl radicals (HO(*)). For each test, air samples were collected using two
      impingers in series kept in an ice bath, containing each 10 mL of 50 mM phosphate
      buffer at pH 7.2. In tests with TPA, that probe was also added to the buffer
      prior to sampling; in the other two tests, probes and additional reactants were
      added immediately after sampling. The concentration of fluorescent byproducts was
      determined fluorometrically. Calibration curves were developed by reacting DCFH
      and AuR with known amounts of H2O2, and using known amounts of 2
      hydroxyterephthalic acid (HTPA) for TPA. Low detection limits (9-13 nM) and
      quantification limits (18-22 nM) were determined for all three probes, which
      presented a linear response in the range 10-500 nM for AuR and TPA, and 100-2000
      nM for DCFH. High collection efficiency (CE) and recovery efficiency (RE) were
      observed for DCFH (CE=RE=100%) and AuR (CE=100%; RE=73%) by sampling from a
      laboratory-developed gas phase H2O2 generator. Interference of co-occurring ozone
      was evaluated and quantified for the three probes by sampling from the outlet of
      an ozone generator. The method was demonstrated by sampling air emitted by two
      portable air cleaners: a strong ozone generator (AC1) and a plasma generator
      (AC2). High ozone levels emitted by AC1 did not allow for simultaneous
      determination of ROS levels due to high background levels associated with ozone
      decomposition in the buffer. However, emitted ROS were quantified at the outlet
      of AC2 using two of the three probes. With AuR, the concentration of peroxides in
      air emitted by the air cleaner was 300 ppt of H2O2 equivalents. With TPA, the
      HO(*) concentration was 47 ppt. This method is best suited to quantify ROS in the
      presence of low ozone levels.

PMID- 25863367
TI  - Novel potentiometric application for the determination of pantoprazole sodium and
      itopride hydrochloride in their pure and combined dosage form.
AB  - Three sensitive and selective polyvinyl chloride (PVC) matrix membrane electrodes
      were developed and investigated. Sensor I was developed using tetraheptylammonium
      bromide (THB) as an anion exchanger with 2-nitrophenyl octyl ether (2-NPOE) as a
      plasticizer for the determination of the anionic drug pantoprazole sodium
      sesquihydrate (PAN). To determine the cationic drug itopride hydrochloride (ITH),
      two electrodes (sensors II and III) were developed using potassium tetrakis(4
      chlorophenyl) borate (KTCPB) as a cation exchanger with dioctyl phthalate (DOP)
      as a plasticizer. Selective molecular recognition components, 2-hydroxypropyl
      beta-cyclodextrin (2-HP betaCD) and 4-tert-butylcalix[8]arene (tBC8), were used
      as ionophores to improve the selectivity of sensors II and III, respectively. The
      proposed sensors had a linear dynamic range of 1*10(-5) to 1*10(-2) mol L(-1)
      with Nernstian slopes of -54.83+/-0.451, 56.90+/-0.300, and 51.03+/-1.909
      mV/decade for sensors I, II and III, respectively. The Nernstian slopes were also
      estimated over the pH ranges of 11-13, 3.5-8 and 4-7 for the three sensors,
      respectively. The proposed sensors displayed useful analytical characteristics
      for the determination of PAN and ITH in bulk powder, in laboratory prepared
      mixtures and in combined dosage forms with clear discrimination from several
      ions, sugars and some common drug excipients. The method was validated according
      to ICH guidelines. Statistical comparison between the results from the proposed
      method and the results from the reference methods showed no significant
      difference regarding accuracy and precision.

PMID- 25863368
TI  - Biochemical oxygen demand measurement by mediator method in flow system.
AB  - Using mediator as electron acceptor for biochemical oxygen demand (BOD)
      measurement was developed in the last decade (BODMed). However, until now, no
      BOD(Med) in a flow system has been reported. This work for the first time
      describes a flow system of BOD(Med) method (BOD(Med)-FS) by using potassium
      ferricyanide as mediator and carbon fiber felt as substrate material for
      microbial immobilization. The system can determine the BOD value within 30 min
      and possesses a wider analytical linear range for measuring glucose-glutamic acid
      (GGA) standard solution from 2 up to 200 mg L(-1) without the need of dilution.
      The analytical performance of the BOD(Med)-FS is comparable or better than that
      of the previously reported BOD(Med) method, especially its superior long-term
      stability up to 2 months under continuous operation. Moreover, the BOD(Med)-FS
      has same determination accuracy with the conventional BOD5 method by measuring
      real samples from a local wastewater treatment plant (WWTP).

PMID- 25863369
TI  - Rapid analysis of ractopamine in pig tissues by dummy-template imprinted solid
      phase extraction coupling with surface-enhanced Raman spectroscopy.
AB  - Ritodrine has similar skeleton structure to ractopamine and it was selected as
      the dummy-template molecule to synthesize the molecular imprinted polymers
      (MIPs). The MIPs exhibited better selectivity to ractopamine than to the dummy
      template molecule: the imprint factor for ractopamine was 8.9, while 7.6 for
      ritodrine. The MIPs were used as sorbents in solid-phase extraction for selective
      enrichment of ractopamine, and some key parameters were optimized. After that, a
      rapid surface-enhanced Raman spectroscopy method was developed for analysis of
      ractopamine and isoxuprine in pig tissue samples. Under the optimal conditions,
      good linearity was achieved in the range of 20.0-200.0 MUg/L for ractopamine and
      isoxsuprine at 842 cm(-1) and 993 cm(-1), respectively. The limits of detection
      were 3.1-4.3 MUg/L, which were lower than the maximum allowed by U. S. Food and
      Drug Administration. The recoveries of ractopamine and isoxsuprine were 72.4
      79.7% and 71.0-78.2% for the spiked pork and pig liver, respectively, while the
      relative standard deviations ranging from 7.4% to 13.0%. The results suggest that
      the proposed method is sensitive and selective, and it has good potential on the
      quantitative analysis of trace amounts of beta-agonists in complex samples.

PMID- 25863370
TI  - Electrochemical detection of benzo(a)pyrene in acetonitrile-water binary medium.
AB  - Electrochemical oxidation of adsorbed benzo(a)pyrene (BaP) on the glassy carbon
      electrode (GCE) was explored in acetonitrile-water. When the GCE was incubated in
      100 nM BaP acetonitrile-water (V(water):V(acetonitrile)=1:1) for 10 min at open
      circuit, and then transferred into blank acetonitrile-water
      (V(water):V(acetonitrile)=1:1, pH= 0.70) for differential pulse voltammetry
      measurement, a distinct oxidation peak at 0.98 V (vs. Ag/AgCl) was observed. The
      peak potential was about 180 mV lower than that in acetonitrile. Importantly, the
      peak current was more than 22 times greater. The effects of water on BaP
      preconcentration on the electrode and electrochemical oxidation were revealed,
      respectively. Based on the results, an electrochemical assay for BaP detection
      was developed. The GCE was respectively incubated in acetonitrile-water
      (V(water):V(acetonitrile)=1:1)with BaP concentration ranged from 0 nM to 1000 nM,
      and then transferred into the corresponding blank acetonitrile-water (pH= 0.70)
      for DPV measurements. When the BaP concentration was increased, an increased
      oxidative current at 0.98 V (vs. Ag/AgCl) was observed, and a detection limit of
      0.67 nM was achieved. Because all other priority polycyclic aromatic hydrocarbons
      could not be electrochemically oxidized at 0.98 V, the electrochemical assay
      showed very high selectivity to BaP. Finally, the developed electrochemical assay
      was successfully applied to determination of BaP in a series of real world
      samples, such as drinking water, tap water, lake water and river water.

PMID- 25863371
TI  - Aptamer-based organic-silica hybrid affinity monolith prepared via "thiol-ene"
      click reaction for extraction of thrombin.
AB  - A novel strategy for preparing aptamer-based organic-silica hybrid monolithic
      column was developed via "thiol-ene" click chemistry. Due to the large specific
      surface area of the hybrid matrix and the simplicity, rapidness and high
      efficiency of "thiol-ene" click reaction, the average coverage density of aptamer
      on the organic-silica hybrid monolith reached 420 pmol MUL(-1). Human alpha
      thrombin can be captured on the prepared affinity monolithic column with high
      specificity and eluted by NaClO4 solution. N-p-tosyl-Gly-Pro-Arg p-nitroanilide
      acetate was used as the sensitive chromogenic substrate of thrombin. The thrombin
      enriched by this affinity column was detected with a detection of limit of 0.01
      MUM by spectrophotometry. Furthermore, the extraction recovery of thrombin at
      0.15 MUM in human serum was 91.8% with a relative standard deviation of 4.0%.
      These results indicated that "thiol-ene" click chemistry provided a promising
      technique to immobilize aptamer on organic-inorganic hybrid monolith and the
      easily-assembled affinity monolithic material could be used to realize highly
      selective recognition of trace proteins.

PMID- 25863372
TI  - An enhanced chemiluminescence resonance energy transfer system based on target
      recycling G-guadruplexes/hemin DNAzyme catalysis and its application in
      ultrasensitive detection of DNA.
AB  - An enhanced chemiluminescence resonance energy transfer (CRET) system based on
      target recycling G-guadruplexes/hemin DNAzyme catalysis was developed for
      ultrasensitive detection of DNA. CRET system consists of luminol as
      chemiluminescent donor, and fluorescein isothiocyanate (FITC) as acceptor. The
      sensitive detection was achieved by using the system consisted of G-riched DNA,
      blocker DNA, and the Nb.BbvCI biocatalyst. Upon addition of target DNA to the
      system, target DNA hybridizes with the quasi-circular DNA structure, and forms a
      DNA duplex. The formation of DNA duplex triggers selective enzymatic cleavage of
      quasi-circular DNA by Nb.BbvCI, resulting in the release of target DNA and two G
      riched DNAzyme segments. Released target DNA then hybridizes with another quasi
      circular DNA structure to initiate the cleavage of the quasi-circular DNA
      structure. Eventually, each target DNA can go through many cycles, resulting in
      the digestion of many quasi-circular DNA structures, generating many G-riched
      DNAzyme segments. G-riched DNAzyme segment products assemble with hemin to form
      stable hemin/G-quadruplexes that exhibit peroxidase-like activity which can
      catalyze the oxidation of luminol by H2O2 to produce CL signals. In the presence
      of FITC, CL of luminol can excite FITC molecules, and thus produced CRET between
      the luminol and FITC. This unique analysis strategy gives a detection limit down
      to 80 fM, which is at least four orders of magnitude lower than that of
      unamplified DNA detection methods.

PMID- 25863373
TI  - Prediction of the hydrophilic antioxidant capacity of tomato pastes from the IR
      and fluorescence excitation-emission spectra of extracts and intact samples.
AB  - The performance of the recently proposed excitation-emission fluorescence method
      was compared to the method using infrared measurements for the evaluation of the
      antioxidant properties of intact samples and extracts that had been obtained from
      tomato pastes. The oxygen radical absorbance capacity assay (ORAC) was applied in
      order to estimate the antioxidant capacity of the extracts, while the Folin
      Ciocalteu reagent was adopted for the evaluation of the total phenolic content.
      The optimal extraction conditions for tomato pastes (three minutes of sonication
      under 80 degrees C) were determined using the central composite design.
      Chemometric models such as the partial least squares regression and its N-way
      variant were further constructed in order to predict the antioxidant capacity or
      total phenolic content of the samples using either the IR or fluorescence
      spectra. The prediction errors that were obtained for the total antioxidant
      content were evaluated as the Trolox equivalents from the ORAC assay and were
      found to be equal to 2.011 (14.21%) for the fluorescence and 2.426 (17.15%) for
      the IR spectra, respectively. The prediction errors of the total phenolic content
      expressed as gallic acid equivalents were 0.067 (10.78%) for the fluorescence and
      0.033 (5.36%) for the IR spectra, which were used as independent variables in the
      regression models. 

PMID- 25863374
TI  - Anticancer drug detection using a highly sensitive molecularly imprinted
      electrochemical sensor based on an electropolymerized microporous metal organic
      framework.
AB  - A simple and highly sensitive approach for the detection of the anti-neoplastic
      drug gemcitabine is presented, based on a one-step electropolymerized molecularly
      imprinted microporous-metal-organic-framework. The sensitive layer was prepared
      by electropolymerization of the aniline moieties of p-aminothiophenol- gold
      nanoparticles on the surface of gold electrodes tethered with p-aminothiophenol,
      in the presence of gemcitabine as a template molecule. Experimental parameters
      that control the performance of the sensor were investigated and optimized. Under
      optimal conditions a calibration curve was obtained in the linear range from 3.8
      fM to 38 nM with a limit of detection of 3 fM. The obtained imprinted sensor has
      the advantages of easy manufacture, high sensitivity and selectivity and good
      reproducibility. Furthermore the feasibility of the proposed technique has been
      investigated on spiked serum samples and infusion solution containing
      gemcitabine.

PMID- 25863375
TI  - Evaluation of vibrational spectroscopic methods to identify and quantify multiple
      adulterants in herbal medicines.
AB  - To counter the growth of herbal medicines adulterated with pharmaceuticals
      crossing borders, rapid, inexpensive and non-destructive analytical techniques,
      that can handle complex matrices, are required. Since mid-infrared (MIR), near
      infrared (NIR) and Raman spectroscopic techniques meet these criteria, their
      performance in identifying adulterants in seized weightloss herbal medicines is
      definitively determined. Initially a validated high pressure liquid
      chromatography methodology was used for reference identification and
      quantification of the adulterants sibutramine H2O.HCl, fenfluramine HCl and
      phenolphthalein. Of 38 products, only sibutramine and phenolphthalein were
      detected by HPLC. The spectroscopic measurements showed Raman was ill-suited due
      to sample burning and emission while NIR lacked adulterant selectivity.
      Conversely, MIR demonstrated apt identification performance, which manifested as
      spectrally meaningful separation based on the presence and type of adulterant
      during principal component analysis (test set validated). Partial least squares
      regression models were constructed from the MIR training sets for sibutramine and
      phenolphthalein - both models fitted the training set data well. Average test set
      prediction errors were 0.8% for sibutramine and 2.2% for phenolphthalein over the
      respective concentration ranges of 1.7-11.7% and 0.9-34.4%. MIR is apposite for
      the screening of anorectic and laxative adulterants and is the most viable
      technique for wider adulterant screening in herbal medicines. 

PMID- 25863376
TI  - Standard addition method based on four-way PARAFAC decomposition to solve the
      matrix interferences in the determination of carbamate pesticides in lettuce
      using excitation-emission fluorescence data.
AB  - The simultaneous determination of two carbamate pesticides (carbaryl and
      carbendazim) and of the degradation product of carbaryl (1-naphthol) in iceberg
      lettuce was achieved by means of PARAFAC decomposition and excitation-emission
      fluorescence matrices. A standard addition method for a calibration based on four
      way data was applied using different dilutions of the extract from iceberg
      lettuce as a fourth way that provided the enough variation of the matrix to carry
      out the four-way analysis. A high fluorescent overlapping existed between the
      three analytes and the fluorophores of the matrix. The identification of two
      fluorescent matrix constituents through the four-way model enabled to know the
      matrix contribution in each dilution of the extract. This contribution was
      subtracted from the previous signals and a subsequent three-way analysis was
      carried out with the tensors corresponding to each dilution. The PARAFAC
      decomposition of these resulting tensors showed a CORCONDIA index equal to 99%.
      For the identification of the analytes, the correlation between the PARAFAC
      spectral loadings and the reference spectra has been used. The trueness of the
      method, in the concentration range studied, was guaranteed because there was
      neither constant nor proportional bias according to the appropriate hypothesis
      tests. The best recovery percentages were obtained with the data from the most
      diluted extract, being the results: 127.6% for carbaryl, 125.55% for carbendazim
      and 87.6% for 1-naphthol. When the solvent calibration was performed, the
      decision limit (CCalpha) and the capability of detection (CCbeta) values, in
      x0=0, were 2.21 and 4.38 MUg L(-1) for carbaryl, 4.87 and 9.64 MUg L(-1) for
      carbendazim; and 3.22 and 6.38 MUg L(-1) for 1-naphthol, respectively, for
      probabilities of false positive and false negative fixed at 0.05. However, these
      values were 5.30 and 10.49 MUg L(-1) for carbaryl, 18.05 and 35.73 MUg L(-1) for
      carbendazim; and 1.92 and 3.79 MUg L(-1) for 1-naphthol, respectively, when the
      matrix-matched calibration using the most diluted extract was carried out in the
      recovery study.

PMID- 25863377
TI  - An amperometric enzyme electrode and its biofuel cell based on a glucose oxidase
      poly(3-anilineboronic acid)-Pd nanoparticles bionanocomposite for glucose
      biosensing.
AB  - A new amperometric enzyme electrode and its biofuel cell were fabricated based on
      a glucose oxidase (GOx)-poly(3-anilineboronic acid) (PABA)-Pd nanoparticles
      (PdNPs) bionanocomposite for biosensing of glucose. Briefly, Pd was electroplated
      on a multiwalled carbon nanotubes (MWCNTs)-modified Au electrode, and the GOx
      PABA-PdNPs bionanocomposite was prepared on the Pd(plate)/MWCNTs/Au electrode
      through the chemical oxidation of a GOx-3-anilineboronic acid adduct by Na2PdCl4,
      followed by electrode-modification with an outer-layer chitosan (CS) film. The
      thus-prepared CS/GOx-PABA-PdNPs/Pd(plate)/MWCNTs/Au electrode exhibited a linear
      amperometric response to glucose concentration from 2.0 MUM to 4.5 mM with a
      sensitivity of 160 MUA/mM/cm(2), sub-MUM detection limit, and excellent
      operation/storage stability in the first-generation biosensing mode, as well as
      excellent analytical performance in the second-generation biosensing mode. The
      good recoveries of glucose obtained from spiked urine samples revealed the
      application potential of our amperometric enzyme electrode. In addition, a
      glucose/O2 biofuel cell was constructed using this enzyme electrode as the anode
      and a Pt/MWCNTs/Au electrode as the cathode, and this biofuel cell as a self
      powered biosensing device showed a linear voltage response to glucose
      concentration from 100 MUM to 13.5 mM with a sensitivity of 43.5 mV/mM/cm(2) and
      excellent operation/storage stability.

PMID- 25863378
TI  - A novel, micro, rapid and direct assay to assess total antioxidant capacity of
      solid foods.
AB  - A novel, micro, rapid and direct procedure to measure the total antioxidant
      capacity of solid foods using 2, 2-diphenyl-1-picrylhydrazyl (DPPH) (mR-QUENCHER
      DPPH) was developed and validated. The mR-QUENCHER-DPPH assay was performed in
      semi-aqueous medium (methanol-Tris buffer) using very small sample amounts (below
      3.6 ug), as estimated by a Bradford reagent-based chemical predictor, and it was
      completed in 10 min at room temperature. The total antioxidant capacity (TAC) of
      solid foods was expressed as scavenging capacity index (SCI, mmol DPPH scavenged
      per kg sample), a theoretical and stoichiometric parameter deduced in this study.
      SCI values measured by mR-QUENCHER-DPPH assay for cereals cous-cous (7.20+/
      0.35), amaranth (7.99+/-0.35) and buckwheat (194.2+/-6.72); Goji fruit (91.27+/
      3.98); lotus root (2402+/-168); and spices turmeric (3767+/-355), ginger (2493+/
      283), and cinnamon (10461+/-2133) were further validated using Folin-Ciocalteau
      assay. Bland-Altman analysis showed that there were not statistically significant
      differences in TAC values as measured by both assays. In the same way, TAC values
      measured by mR-QUENCHER-DPPH were correlated with free (r=0.8088, P=0.0151),
      bound (r=0.9668, P<0.0001) and total (r=0.9067, P=0.0019) reducing capacity of
      extracts from solid foods as assessed by Folin-Ciocalteau assay. The mR-QUENCHER
      DPPH assay allows to measure TAC values using micro-gram amounts in solid food
      samples with a wide content range of antioxidants (low, high and very high), and
      omitting the time-consuming dilution cellulose-step commonly employed in the
      traditional QUENCHER procedures.

PMID- 25863380
TI  - Ionization of solutions using mechanical spray in collison nebulizer: a new
      simple ion source for mass-spectrometric analysis.
AB  - Ionization methods for mass-spectrometric analysis based on mechanical liquid
      spray by a high-speed gas flow (like Sonic Spray Ionization (SSI)) offer some
      advantages over other ionization methods. Among these one should mention the
      absence of electric voltage, radioactive sources and heaters. In this paper we
      suggest using the Collison nebulizer for solution ionization via mechanical
      spray. Research results into the efficiency of the Collison spray ionization of
      different solvents used in chemical synthesis are submitted. It is shown that an
      increase in dipole moment of the solvent molecules leads to increased ionization
      efficiency for all solvents tested, except water. This seems to result from
      anomaly high surface tension and vaporization enthalpy for water. High
      concentrations (>10(-4) g/ml) of both inorganic salts (NaCl, K2SO4) and organic
      additive (morphine) give a decrease in the total ion current at the Collison
      nebulizer outlet. This is assumed to be due both to an increased droplet size of
      aerosol produced upon spraying and a low dipole moment of an ion-solvation shell
      complex. Mass-spectra of aqueous K2SO4 and morphine (C17H19NO3) were obtained
      with the Collison nebulizer. These spectra contained non-identified background
      peaks along with the peaks of K(+) and H(+)C17H19NO3 that were likely to result
      from the water ionization and presence of uncontrolled impurities. A relationship
      between the intensity of mass-spectroscopic peaks of the ions of potassium and
      morphine and the concentration of appropriate aqueous solution was determined.
      Mass-spectrometric analysis using the Collison spray ionization gave a detection
      limit for morphine ~10(-8) g/ml and a linear response range for protonated
      molecular ion (H(+)C17H19NO3 with m/z=286 from 10(-8) g/ml to 2*10(-7) g/ml.

PMID- 25863379
TI  - Integrated strong cation-exchange hybrid monolith coupled with capillary zone
      electrophoresis and simultaneous dynamic pH junction for large-volume proteomic
      analysis by mass spectrometry.
AB  - A sulfonate-silica hybrid strong cation-exchange (SCX) monolith was synthesized
      at the proximal end of a capillary zone electrophoresis column and used for on
      line solid-phase extraction (SPE) sample preconcentration. Sample was prepared in
      an acidic buffer and deposited onto the SCX-SPE monolith and eluted using a basic
      buffer. Electrophoresis was performed in an acidic buffer. This combination of
      buffers results in formation of a dynamic pH junction, which allows use of
      relatively large elution buffer volume while maintaining peak efficiency and
      resolution. All experiments were performed with a 50 um ID capillary, a 1cm long
      SCX-SPE monolith, a 60cm long separation capillary, and a electrokinetically
      pumped nanospray interface. The volume of the capillary is 1.1 uL. By loading 21
      uL of a 1*10(-7) M angiotensin II solution, an enrichment factor of 3000 compared
      to standard electrokinetic injection was achieved on this platform while
      retaining efficient electrophoretic performance (N=44,000 plates). The loading
      capacity of the sulfonate SCX hybrid monolith was determined to be ~15 pmol by
      frontal analysis with 10(-5) M angiotensin II. The system was also applied to the
      analysis of a 10(-4) mg/mL bovine serum albumin tryptic digest; the protein
      coverage was 12% and 11 peptides were identified. Finally, by loading 5.5 uL of a
      10(-3) mg/mL E. coli digest, 109 proteins and 271 peptides were identified in a
      20 min separation; the median separation efficiency generated by these peptides
      was 25,000 theoretical plates.

PMID- 25863381
TI  - Crown ether-modified electrodes for the simultaneous stripping voltammetric
      determination of Cd(II), Pb(II) and Cu(II).
AB  - This work describes the immobilization of 4-carboxybenzo-18-crown-6 (CB-18-crown
      6) and 4-carboxybenzo-15-crown-5 (CB-15-crown-5) assisted by lysine on aryl
      diazonium salt monolayers anchored to the surface of graphite-epoxy composite
      electrodes (GEC), and their use for the simultaneous determination of Cd(II),
      Pb(II) and Cu(II) by differential pulse anodic stripping voltammetry (DPASV).
      These modified electrodes display a good repeatability and reproducibility with
      detection and quantification limits at levels of ug L(-1) (ppb), confirming their
      suitability for the determination of Cd(II), Pb(II) and Cu(II) ions in
      environmental samples. The overlapped nature of the multimetal stripping
      measurements was resolved by employing the two-sensor array CB-15-crown-5-GEC and
      CB-18-crown-6-GEC, since the metal complex selectivity exhibited by the
      considered ligands could add some discrimination power. For the processing of the
      voltammograms, Discrete Wavelet Transform and Causal Index were selected as
      preprocessing tools for data compression coupled with an artificial neural
      network for the modeling of the obtained responses, allowing the resolution of
      mixtures of these metals with good prediction of their concentrations
      (correlation with expected values for an external test subset better than 0.942).

PMID- 25863382
TI  - Synthesis of divinylbenzene polymer/Fe3O4 hybrid monolithic column for enrichment
      and online thermal desorption of methylmercury in real samples.
AB  - A novel method of divinylbenzene polymer (DVB)/Fe3O4 hybrid monolithic column
      solid phase extraction and on line thermal desorption was developed to analyze
      methylmercury (MeHg) in water and fish samples. The monolithic column was
      prepared by in situ polymerization in silica tube and its heating characteristic
      was studied in detail. Special accent was put on the study of parameters
      influencing adsorption and desorption of MeHg, such as pH, flow rate of sample
      solution, temperature of desorption and flow rate of carrier. Under optimum
      conditions, the detection limit and relative standard deviation of MeHg were 0.09
      ng L(-1) and 2.6% (10 ng L(-1), N=11), respectively. Recoveries of MeHg were
      never less than 96%. Standard reference material GBW10029 was analyzed for
      validation of the methodology. This method was successfully applied to the
      determination of MeHg in water and fish samples.

PMID- 25863383
TI  - A label-free fluorescence turn-on sensor for rapid detection of cysteine.
AB  - A Hg(2+)-mediated fluorescence turn-on sensor for cysteine (Cys) detection was
      developed using the nucleic acid minor groove binding dye DAPI. In this work, two
      fully complementary DNA sequences, a T-rich single-stranded molecule (ssDNA) and
      an A-rich single-stranded molecule, were employed to constitute consecutive
      "AT/TA" base pairs, which could strongly enhance the fluorescence of DAPI. In the
      absence of cysteine, Hg(2+) reacted with T-rich single-stranded DNA and "T-Hg(2+)
      T" base pairs formed, this seriously disrupted consecutive AT base pairs. As a
      result, the fluorescence of DAPI was not increased efficiently. However,
      considering that cysteine binds strongly to Hg(2+), the structure of the "T
      Hg(2+)-T" complexes was destroyed in the presence of cysteine, resulting in the
      re-formation of consecutive AT base pairs and increased DAPI fluorescence.
      Obviously, the amount of cysteine could be easily measured based on the
      enhancement of DAPI fluorescence, and it took only 20 min to complete the whole
      cysteine-sensing process. Therefore, a label-free fluorescent "turn-on" sensor
      for the rapid detection of cysteine was designed, and the detection limit of this
      sensor was as low as 2.4 nM, which was much lower than those of the most of the
      previously reported cysteine sensors.

PMID- 25863384
TI  - Electrokinetic acceleration of DNA hybridization in microsystems.
AB  - In this work, electrokinetic acceleration of DNA hybridization was investigated
      by different combinations of frequencies and amplitudes of actuating electric
      signals. Because the frequencies from low to high can induce different kinds of
      electrokinetic forces, i.e., electroosmotic to electrothermal forces, this work
      provides an in-depth investigation of electrokinetic enhanced hybridization.
      Concentric circular Cr/Au microelectrodes of 350 um in diameter were fabricated
      on a glass substrate and probe DNA was immobilized on the electrode surface.
      Target DNA labeled with fluorescent dyes suspending in solution was then applied
      to the electrode. Different electrokinetic forces were induced by the application
      of different electric signals to the circular microelectrodes. Local microfluidic
      vortexes were generated to increase the collision efficiency between the target
      DNA suspending in solution and probe DNA immobilized on the electrode surface.
      DNA hybridization on the electrode surface could be accelerated by the
      electrokinetic forces. The level of hybridization was represented by the
      fluorescent signal intensity ratio. Results revealed that such 5-min dynamic
      hybridization increased 4.5 fold of signal intensity ratio as compared to a 1-h
      static hybridization. Moreover, dynamic hybridization was found to have better
      differentiation ability between specific and non-specific target DNA. This study
      provides a strategy to accelerate DNA hybridization in microsystems.

PMID- 25863385
TI  - Confocal Raman spectrocopy for the analysis of nail polish evidence.
AB  - Nail polishes are cosmetic paints that may be susceptible of forensic analysis
      offering useful information to assist in a crime reconstruction. Although the
      nail polish appearance could allow a quick visual identification of the sample,
      this analysis is subjected to the perception and subjective interpretation of the
      forensic examiner. The chemical analysis of the nail polishes offers great deal
      of information not subjected to analyst interpretation. Confocal Raman
      spectroscopy is a well-suited technique for the analysis of paints due to its non
      invasive and non-destructive nature and its ability to supply information about
      the organic and inorganic components of the sample. In this work, 77 regular and
      gel nail polishes were analyzed with confocal Raman spectroscopy using two laser
      wavelengths (532 and 780 nm). The sample behavior under the two laser wavelengths
      and the differences in the spectra taken at different points of the sample were
      studied for each nail polish. Additionally, the spectra obtained for all the nail
      polishes were visually compared. The results concluded that the longer laser
      wavelength prevents sample burning and fluorescence effects; the similarity among
      the spectra collected within the sample is not directly related with the presence
      of glitter particles; and 64% of the samples analyzed showed a characteristic
      spectrum. Additionally, the use of confocal Raman spectroscopy for the forensic
      analysis of nail polishes evidence in the form of flakes or smudges on different
      surfaces were studied. The results showed that both types of evidence can be
      analyzed by the technique. Also, two non-invasive sampling methods for the
      collection of the evidence from the nails of the suspect or the victim were
      proposed: (i) to use acetone-soaked cotton swabs to remove the nail varnishes and
      (ii) to scrape the nail polish from the nail with a blade. Both approaches, each
      exhibiting advantages and drawbacks in terms of transport and handling were
      appropriate for a further chemical analysis of the samples.

PMID- 25863386
TI  - Label-free nucleic acids detection based on DNA templated silver nanoclusters
      fluorescent probe.
AB  - Based on DNA templated Ag NCs (DNA/Ag NCs) fluorescent probe, a label-free
      fluorescent method was developed for the detection of clinical significant DNA
      fragments from human immunodeficiency virus type 1 (HIV-1) DNA. Firstly, a
      hairpin probe, containing target DNA recognition sequence and guanine-rich
      sequence, was designed to hybridize with the target DNA and form a blunt 3'
      terminus DNA duplex. Then, exonuclease III (Exo III) was employed to stepwise
      hydrolyze the mononucleotides from formed blunt 3'-terminus DNA duplex, releasing
      the target DNA and guanine-rich sequence. Finally, DNA/Ag NCs fluorescent probe
      was introduced to hybridize with the guanine-rich sequence, leading to an
      enhanced fluorescence signal for detection. The proposed method could detect as
      low as 2.9*10(-10) mol L(-1) HIV-1 DNA and exhibited excellent selectivity
      against mismatched target DNA. Furthermore, the method possessed perfect
      recoveries in cells lysate and human serum, showing potential to be used in
      biological samples.

PMID- 25863387
TI  - High-selective and sensitive voltammetric sensor for butylated hydroxyanisole
      based on AuNPs-PVP-graphene nanocomposites.
AB  - Gold nanoparticles (AuNPs) and reduced graphene oxide (graphene) composites were
      synthesized via a simple one-pot approach in the presence of polyvinylpyrrolidone
      (PVP). Further, the Au-PVP-graphene nanocomposite was used as a new sensing
      material for the electrochemical detection of butylated hydroxyanisole (BHA).
      Because of the greatly enlarged surface area, the enhanced electron transfer
      rate, and a stronger enrichment of BHA, the sensor based on Au-PVP-graphene
      modified glassy carbon electrode (GCE) displayed highly sensitive electrochemical
      responses to BHA. Applying linear sweep voltammetry, a good linear relationship
      of the oxidation peak current with respect to concentrations of BHA across the
      range of 0.2-100.0 uM and a detection limit of 0.04 uM was achieved. The
      practical analytical performance of the Au-PVP-graphene/GCE was examined by
      evaluating detection of BHA in soybean oil and the flour samples. Satisfactory
      results revealed that this work offered a new way for the sensitive and simple
      determination of BHA in complex samples.

PMID- 25863388
TI  - A new spot quality control for protein macroarray based on immunological
      detection.
AB  - Protein macroarray is a new, simple and multiple biochemistry detection system,
      in which the test spots are more than 1mm diameter and results directly visible
      and instrumentation is not necessary. This technology, however, possesses
      recognized problems with spot quality and uniformity, issues that can limit its
      application. Previous methods have been developed for spot quality control, but
      they are complicated or require specific instrumentation. Therefore, we have
      developed a spot quality control buffer supplement with Ponceau S (SQCB-PS) as a
      direct and visible means of monitoring spot quality on nitrocellulose membrane
      prior to hybridization. In this report, 1% (w/v) Ponceau S and 10% (v/v) glycerol
      in spotting buffer were found to be optimal for spot quality control and food
      borne pathogens multiple detection. Furthermore, the sensitivity and specificity
      of the protein macroarray were not compromised by spotting buffer with Ponceau S.
      Under optimal conditions, this visible spot quality control method makes the
      detection more reliable, and should enhance the wider use of the technique. 

PMID- 25863389
TI  - Antibacterial effect of various shapes of silver nanoparticles monitored by SERS.
AB  - A comparative evaluation of antimicrobial effect of synthesized silver
      nanoparticles (AgNPs) of different shapes using different methods was performed.
      Spherical, triangular and hexagonal AgNPs with an average size of 40 nm were
      chemically prepared and characterized by transmission electron microscope (TEM)
      and UV-visible spectroscopy. The antimicrobial effect of these different AgNPs
      against the gram negative bacterium Escherichia coli (E. coli) was studied by
      surface enhanced Raman spectroscopy (SERS), the evaluation of growth curves and
      inhibition zones. SERS proved to be sensitive to monitor the changes that
      occurred in the bacterial cells upon interaction with AgNPs, which qualitatively
      compared well with the data provided by the reference methods. However, as SERS
      is already sensitive to initial changes in the chemistry of bacteria due to the
      antibacterial effect of the AgNPs, fast and detailed information is provided by
      SERS as opposed to the classical reference methods based on the evaluation of
      growth curves and inhibition zones. The results of this work also demonstrate
      that hexagonal AgNPs display the highest antibacterial effect when compared to
      other NPs shapes, with triangular AgNPs exhibiting no antibacterial effect under
      the adopted conditions.

PMID- 25863390
TI  - Determination of polycyclic aromatic hydrocarbons using lab on valve dispersive
      liquid-liquid microextraction coupled to high performance chromatography.
AB  - In this work, dispersive liquid-liquid microextraction (DLLME) method was applied
      for high performance liquid chromatography (HPLC) determination of 15 PAHs in
      aqueous matrices.The extraction procedure was automated using a system of
      multisyringe flow injection analysis coupled to HPLC instrument with fluorescence
      detector. Factors affecting the extraction process, such as type and volume of
      extraction and dispersive solvent, extraction time and centrifugation step were
      investigated thoroughly and optimized utilizing factorial design. The best
      recovery was achieved using 100 uL of trichloroethylene as the extraction solvent
      and 900 uL of acetonitrile as the dispersive solvent.The results showed that
      extraction time has no effect on the recovery of PAHs. The enrichment factors of
      PAHs were in the range of 86-95 with limits of detection of 0.02-0.6 ug L(-1).
      The linearity was 0.2-600 ug L(-1) for different PAHs. The relative standard
      deviation (RSD) for intra- and inter-day of extraction of PAHs were in the range
      of 1.6-4.7 and 2.1-5.3, respectively, for five measurements.The developed method
      was used to assess the occurrence of 15 PAHs in tap water, rain waters and river
      surface waters samples.

PMID- 25863391
TI  - Optimization and validation of a method for the determination of the refractive
      index of milk serum based on the reaction between milk and copper(II) sulfate to
      detect milk dilutions.
AB  - We report the use of a method to determine the refractive index of copper(II)
      serum (RICS) in milk as a tool to detect the fraudulent addition of water. This
      practice is highly profitable, unlawful, and difficult to deter. The method was
      optimized and validated and is simple, fast and robust. The optimized method
      yielded statistically equivalent results compared to the reference method with an
      accuracy of 0.4% and quadrupled analytical throughput. Trueness, precision
      (repeatability and intermediate precision) and ruggedness are determined to be
      satisfactory at a 95.45% confidence level. The expanded uncertainty of the
      measurement was +/-0.38 degrees Zeiss at the 95.45% confidence level (k=3.30),
      corresponding to 1.03% of the minimum measurement expected in adequate samples
      (>37.00 degrees Zeiss). 

PMID- 25863392
TI  - Silver nanoparticles-enhanced rare earth co-luminescence effect of Tb(III)-Y(III)
      dopamine system.
AB  - It was found that silver nanoparticles (AgNPs) could enhance co-luminescence
      effect of rare earths ions Tb(3+) and Y(3+). Based on this, a sensitive
      fluorescence detection method for the determination of dopamine (DA) was
      proposed. Moreover, the detection limit for DA was very low (down to nM). This is
      because DA can remarkably enhance the luminescence intensity of the Tb(3+) ion by
      Y(3+) in the colloidal solution of AgNPs, forming a new co-luminescence system.
      Furthermore, based on the metal enhanced fluorescence (MEF), AgNPs can sensitize
      the co-luminescence effect of the complex of Tb(3+)-Y(3+)-DA. In a neutral buffer
      solution (pH 7.50), the luminescence intensity of the system was linearly related
      to the concentration of DA in the range of 2.0-100 nM, with a limit of detection
      as low as 0.57 nM. The proposed method was applied for the determination of DA in
      dopamine hydrochloride injections and human serum samples with good accuracy and
      satisfactory recovery.

PMID- 25863393
TI  - Electrochemical and spectroscopic studies of ssDNA damage induced by hydrogen
      peroxide using graphene based nanomaterials.
AB  - The oxidative damage of deoxyribonucleic acid (DNA) has been intensively studied
      due to its role in the occurrence of some diseases. The hydrogen peroxide (H2O2)
      is one of the reactive oxygen species (ROS). It can induce oxidation of DNA
      bases, sugar lesions or DNA strand breaks. The Pt/Gr-Au-3 modified electrode was
      employed for the analysis of four ssDNA samples: single-stranded DNA (ssDNA),
      ssDNA pre-treated with hydrogen peroxide (ssDNA-H2O2), ssDNA pre-treated with
      graphene-gold nanoparticles (ssDNA-Gr-Au) and ssDNA-Gr-Au complex pre-treated
      with hydrogen peroxide (ssDNA-Gr-Au-H2O2). By monitoring the changes of the
      purine oxidation peaks currents, we obtained valuable information about the
      damage induced by the hydrogen peroxide onto the un-treated or graphene pre
      treated ssDNA and also about the interaction between ssDNA and graphene-based
      nanomaterial. The FTIR analysis has been also used to obtain information about
      the ssDNA damage. These findings allowed us to prove the utility of graphene
      based nanomaterials (mainly Gr-Au-3) not only for the investigation of the
      oxidative damage induced by a non-radical oxidant, but also for the determination
      of the type of interaction between ssDNA and graphene surface. The stability of
      the ssDNA-Gr-Au-3 complex against the damage induced by H2O2, in the absence of
      reduced transition metals, was also established. 

PMID- 25863394
TI  - Lead determination at ng/mL level by flame atomic absorption spectrometry using a
      tantalum coated slotted quartz tube atom trap.
AB  - Flame atomic absorption spectrometry (FAAS) still keeps its importance despite
      the relatively low sensitivity; because it is a simple and economical technique
      for determination of metals. In recent years, atom traps have been developed to
      increase the sensitivity of FAAS. Although the detection limit of FAAS is only at
      the level of ug/mL, with the use of atom traps it can reach to ng/mL. Slotted
      quartz tube (SQT) is one of the atom traps used to improve sensitivity. In atom
      trapping mode of SQT, analyte is trapped on-line in SQT for few minutes using
      ordinary sample aspiration, followed by the introduction of a small volume of
      organic solvent to effect the revolatilization and atomization of analyte species
      resulting in a transient signal. This system is economical, commercially
      available and easy to use. In this study, a sensitive analytical method was
      developed for the determination of lead with the help of SQT atom trapping flame
      atomization (SQT-AT-FAAS). 574 Fold sensitivity enhancement was obtained at a
      sample suction rate of 3.9 mL/min for 5.0 min trapping period with respect to
      FAAS. Organic solvent was selected as 40 uL of methyl isobutyl ketone (MIBK). To
      obtain a further sensitivity enhancement inner surface of SQT was coated with
      several transition metals. The best sensitivity enhancement, 1650 fold
      enhancement, was obtained by the Ta-coated SQT-AT-FAAS. In addition, chemical
      nature of Pb species trapped on quartz and Ta surface, and the chemical nature of
      Ta on quartz surface were investigated by X-ray photoelectron spectroscopy (XPS)
      and Raman Spectroscopy. Raman spectrometric results indicate that tantalum is
      coated on SQT surface in the form of Ta2O5. XPS studies revealed that the
      oxidation state of Pb in species trapped on both bare and Ta coated SQT surfaces
      is +2. For the accuracy check, the analyses of standard reference material were
      performed by use of SCP SCIENCE EnviroMAT Low (EU-L-2) and results for Pb were to
      be in good agreement with the certified value using SQT-AT-FAAS and Ta coated
      SQT.

PMID- 25863395
TI  - A signal-on fluorescent aptasensor based on single-stranded DNA-sensitized
      luminescence of terbium (III) for label-free detection of breast cancer cells.
AB  - Breast cancer is the most common type of malignant tumor in women. Recently, it
      has been shown that detection of breast cancer tumor cells outside the primitive
      tumor is an effective early diagnosis with great prognostic and clinical utility.
      For this purpose, we developed a signal-on fluorescence aptasensor for label
      free, facile and sensitive detection of MCF-7 breast cancer cells. Due to target
      aptamer specific recognition and single-stranded DNA-sensitized luminescence of
      terbium (III), the proposed aptasensor exhibits excellent sensitivity with
      detection limit as low as 70 cells mL(-1). Compared with common organic dyes and
      the emerging nano-technological probes, the combination of terbium (III) and
      single-stranded DNA signal probe (Tb(3+)-SP) serves as a more powerful bio-probe
      because of its stable optical property, good biocompatibility and free from
      complex synthesis. The feasibility investigations have illustrated the potential
      applicability of this aptasensor for selective and sensitive detection of MCF-7
      breast cancer cells. Moreover, this proposed aptasensor can be also extended for
      the determination of other tumor cancers or bio-molecules by altering
      corresponding aptamers. Taken together, this easy-to-perform aptasensor may
      represent a promising way for early screening and detection of tumor cancers or
      other bio-molecules in clinical diagnosis.

PMID- 25863396
TI  - Development of liquid chromatography methods coupled to mass spectrometry for the
      analysis of substances with a wide variety of polarity in meconium.
AB  - Meconium is the first fecal excretion of newborns. This complex accumulative
      matrix allows assessing the exposure of the fetus to xenobiotics during the last
      6 months of pregnancy. To determine the eventual effect of fetal exposure to
      micropollutants in this matrix, robust and sensitive analytical methods must be
      developed. This article describes the method development of liquid chromatography
      methods coupled to triple quadrupole mass spectrometry for relevant pollutants.
      The 28 selected target compounds had different physico-chemical properties from
      very polar (glyphosate) to non-polar molecules (pyrethroids). Tests were
      performed with three different types of columns: reversed phase, ion exchange and
      HILIC. As a unique method could not be determined for the simultaneous analysis
      of all compounds, three columns were selected and suitable chromatographic
      methods were optimized. Similar results were noticed for the separation of the
      target compounds dissolved in either meconium extract or solvent for reversed
      phase and ion exchange columns. However, for HILIC, the matrix had a significant
      influence on the peak shape and robustness of the method. Finally, the analytical
      methods were applied to "real" meconium samples. 

PMID- 25863397
TI  - Development of a Stationary Phase Optimised Selectivity Liquid Chromatography
      based screening method for adulterations of food supplements for the treatment of
      pain.
AB  - Illegally adulterated dietary supplements are an increasing problem worldwide.
      One of the important groups of often adulterated products are the dietary
      supplements, sold for the treatment of pain. These often contain analgesics, a
      heterogeneous group of molecules, containing both hydrophilic and hydrophobic
      compounds. The development of a screening method for these components, especially
      when mass spectrometric detection is not available, necessitates chromatographic
      separation, difficult to achieve with traditional chromatographic columns. In
      this paper Stationary Phase Optimised Selectivity Liquid Chromatography was used
      for the development of a screening method for nine analgesics, codeine and
      caffeine, often present in this type of dietary supplements. The method shows a
      good separation of all the compounds, allowing the screening to be performed with
      diode array detection and is fully compatible with mass spectrometry. The method
      was validated for its selectivity following the guidelines as described for the
      screening of pesticide residues and residues of veterinary medicines in food. 

PMID- 25863398
TI  - Improved sample treatment for the determination of 17 strong sorbed quinolone
      antibiotics from compost by ultra high performance liquid chromatography tandem
      mass spectrometry.
AB  - The use of compost from sewage sludge for agricultural application is nowadays
      increasing, since composting is recognized as one of the most important recycling
      options for this material, being a source of nutrients for plants but also of
      contamination by persistent pollutants. In the present work, a multi-residue
      analytical method for the determination of 17 quinolone antibiotic residues in
      compost using multivariate optimization strategies and ultra high performance
      liquid chromatography-tandem mass spectrometry has been developed. It is based on
      the use of microwave-assisted extraction at drastic conditions with ACN:m
      phosphoric acid (1% w/v) for 5 min at 120 degrees C, in order to achieve a
      quantitative extraction of the compounds (>76% of extraction recovery). Extracts
      were cleaned-up by salt-assisted liquid-liquid extraction (SALLE) with NaCl at pH
      1.5 (with HClO4) and then using a dispersive sorbent (PSA). After LC separation,
      the MS conditions, in positive electrospray ionization mode (ESI), were
      individually optimized for each analyte to obtain maximum sensitivity in the
      selected reaction monitoring mode (SRM). The analytes were separated in less than
      7 min. Cincophen was used as surrogate standard. The limits of detection ranged
      from 0.2 to 0.5 ng g(-1), and the limits of the quantification from 0.5 to 1.5 ng
      g(-1), while intra- and inter-day variability (% RSD) was under 7% in all cases.
      A recovery assay was performed with spiked samples. Recoveries ranging from 95.3%
      to 106.2% were obtained. Cleanup procedure reduced significantly matrix effects,
      which constitutes an important achievement, considering the important drawbacks
      of matrix components in quality and validation parameters. This method was
      applied to several commercial compost samples. Only 6 of the studied antibiotics
      were not detected in any of the samples. The antibiotics with the highest
      concentrations were ciprofloxacin (836 ng g(-1)), ofloxacin (719 ng g(-1)), and
      enrofloxacin (674 ng g(-1)), which were also the only ones found in all the
      analyzed samples. The results showed that this method could also be potentially
      adapted for the analysis of other strong sorbed basic pharmaceuticals in solid
      environmental matrices.

PMID- 25863399
TI  - Determination of sulfonamides in serum by on-line solid-phase extraction coupled
      to liquid chromatography with photoinduced fluorescence detection.
AB  - An analytical method based on on-line solid-phase extraction coupled to liquid
      chromatography with photoinduced fluorescence detection has been developed to
      determine sulfonamides in serum. A home-made setup was used to percolate 3 mL of
      sample through a solid-phase extraction column. Analytes were retained onto the
      sorbent by an anion exchange mechanism which ensures an optimum compatibility
      with the subsequent chromatographic separation using a C-18 column and an on-line
      photoreactor in order to derivatize sulfonamides, which do not present native
      fluorescence. The method allowed the determination of 7 sulfonamides in serum
      samples previously deproteinized in less than 18 min and with limits of detection
      ranging between 1.8 and 3.6 mg/L. Relative recoveries between 91.5% and 102.1%
      were obtained with satisfactory precision since relative standard deviations were
      always below 10.5%.

PMID- 25863400
TI  - Multivariate analysis of coconut residues by near infrared spectroscopy.
AB  - Near infrared (NIR) spectroscopy was used to determine the content of Klason
      lignin, acid-soluble lignin, total lignin, extractives, ash, acid-insoluble
      residue, glucose, xylose, rhamnose, galactose, arabinose, mannose and total
      sugars in coconut residues. The samples were analyzed at several processing
      stages: wet unground (WU), dried unground (DU) and dried and sieved (DS). Partial
      least squares models were built, and the models for the analytes exhibited
      R(2)>0.80, with the exceptions of rhamnose, arabinose, galactose, mannose and ash
      from all fractions, and the lignin content from the WU fraction, which were
      predicted poorly (R(2)<0.70). There were some significant differences between the
      models for the main lignocellulosic components at the various stages of biomass.
      These results proved that NIR spectroscopy is useful for analysis at
      biorefineries, and it can be used as a faster and more economical alternative to
      the standard methods. 

PMID- 25863401
TI  - Bi-functionalized aptasensor for ultrasensitive detection of thrombin.
AB  - A novel bi-functionalized aptasensor for thrombin detection was fabricated by
      using electrochemiluminescence (ECL) and electrochemical impedance spectroscopy
      (EIS) techniques. A thiol-terminated aptamer with 15 oligonucleotides was
      hybridized with its complementary oligonucleotides to form a double-stranded DNA
      (dsDNA). Then, the thiol-labeled dsDNA was assembled on a Au electrode via Au-S
      bond; the other distal of the dsDNA labeled with biotin was bound to QDs through
      a biotin-avidin conjugation. When thrombin is present in the detection solution,
      the aptamer can combine with thrombin, resulting in loss of CdSe QDs from the
      electrode surface and thereby decreasing the ECL intensity and increasing the
      impedance. The decreased ECL and increased EIS signals are logarithmically linear
      with respect to the concentration of thrombin. The linear range was 10(-10)-10(
      3) MUg mL(-1) (R=0.9924) for the ECL signal and 10(-10)-10(-1) MUg mL(-1)
      (R=0.9875) for the EIS method with a common detection limit of 10(-10) MUg mL(-1)
      (2.7 aM). In addition, the bi-functionalized aptasensor exhibited excellent
      selectivity, super sensitivity, a low detection limit and a wide linear range.

PMID- 25863402
TI  - Direct solid sampling system for electrothermal vaporization and its application
      to the determination of chlorine in nanopowder samples by inductively coupled
      plasma optical emission spectroscopy.
AB  - An electrothermal vaporization (ETV) system using a tungsten boat furnace (TBF)
      sample cuvette was designed for the direct determination of chlorine in metallic
      nanopowders and fine powder samples with detection by inductively coupled plasma
      optical emission spectroscopy (ICP-OES). A portion of a powder or particle sample
      was placed into a small tungsten sample cuvette and weighed accurately. A
      modifier solution of aqueous or alcoholic potassium hydroxide was added to it.
      Then, the cuvette was positioned on the TBF incorporated into the ETV apparatus.
      The analyte was vaporized and introduced into the ICP optical emission
      spectrometer with a carrier gas stream of argon and hydrogen. The metal samples
      were analyzed by using an external calibration curve prepared from aqueous
      standard solutions. Few chemical species including analyte and some chlorine-free
      species were introduced into the ICP, because the analyte has been separated from
      the matrix before introduction. Under such dry plasma conditions, the energy of
      plasma discharge was focused on the excitation of chlorine atoms, and as a
      result, lower detection limits were achieved. A detection limit of 170 ng g(-1)
      of chlorine in solid metal samples was established when 60 mg sample was used.
      The relative standard deviation for 16 replicate measurements obtained with 100
      ng chlorine was 8.7%. Approximately 30 batches could be vaporized per hour. The
      analytical results for various nanopowders (iron (III) oxide, copper, silver, and
      gold) and metallic fine powder samples (silver and gold) are described.

PMID- 25863403
TI  - Analysis of milk by FT-Raman spectroscopy.
AB  - Fat, protein, carbohydrates and dry matter were quantified in commercial bovine
      milk samples, with the relative standard errors of prediction (RSEP) in the 3.4
      6.1% range, using the partial least squares (PLS) method based on Raman spectra
      of liquid milk samples. Results of a better quality were obtained from a PLS
      model derived from IR spectra registered using single reflection ATR diamond
      accessory, which yielded RSEP values of 2.4-4.4%. The data indicated IR single
      reflection ATR spectroscopy and Raman spectroscopy in combination with
      multivariate modelling using the PLS method, allowed for the reliable,
      simultaneous quantitative determination of macronutrients in milk. The low signal
      to noise ratio of Raman spectra affects the quality of fat quantification
      especially for strongly defatted milk samples. 

PMID- 25863404
TI  - Target analysis of primary aromatic amines combined with a comprehensive
      screening of migrating substances in kitchen utensils by liquid chromatography
      high resolution mass spectrometry.
AB  - An analytical strategy including both the quantitative target analysis of 8
      regulated primary aromatic amines (PAAs), as well as a comprehensive post-run
      target screening of 77 migrating substances, was developed for nylon utensils,
      using liquid chromatography-orbitrap-high resolution mass spectrometry (LC-HRMS)
      operating in full scan mode. The accurate mass data were acquired with a
      resolving power of 50,000 FWHM (scan speed, 2 Hz), and by alternating two
      acquisition events, ESI+ with and without fragmentation. The target method was
      validated after statistical optimization of the main ionization and fragmentation
      parameters. The quantitative method presented appropriate performance to be used
      in official monitoring with recoveries ranging from 78% to 112%, precision in
      terms of Relative Standard Deviation (RSD) was less than 15%, and the limits of
      quantification were between 2 and 2.5 ug kg(-1). For post-target screening, a
      customized theoretical database was built for food contact material migrants,
      including bisphenols, phthalates, and other amines. For identification purposes,
      accurate exact mass (<5 ppm) and some diagnostic ions including fragments were
      used. The strategy was applied to 10 real samples collected from different
      retailers in the Valencian Region (Spain) during 2014. Six out of eight target
      PAAs were detected in at least one sample in the target analysis. The most
      frequently detected compounds were 4,4'-methylenedianiline and aniline, with
      concentrations ranging from 2.4 to 19,715 ug kg(-1) and 2.5 to 283 ug kg(-1),
      respectively. Two phthalates were identified and confirmed in the post-run target
      screening analysis.

PMID- 25863405
TI  - Evaluation of 4 Commercial Viewing Devices for Radiographic Perceptibility and
      Working Length Determination.
AB  - INTRODUCTION: This study compared images displayed on 1 desktop monitor, 1 laptop
      monitor, and 2 tablets for the detection of contrast and working length
      interpretation, with a null hypothesis of no differences between the devices.
      METHODS: Three aluminum blocks, with milled circles of varying depth, were
      radiographed at various exposure levels to create 45 images of varying
      radiographic density. Six observers viewed the images on 4 devices: Lenovo M92z
      desktop (Lenovo, Beijing, China), Lenovo Z580 laptop (Lenovo), iPad 3 (Apple,
      Cupertino, CA), and iPad mini (Apple). Observers recorded the number of circles
      detected for each image, and a perceptibility curve was used to compare the
      devices. Additionally, 42 extracted teeth were imaged with working length files
      affixed at various levels (short, flush, and long) relative to the anatomic apex.
      Observers measured the distance from file tip to tooth apex on each device. The
      absolute mean measurement error was calculated for each image. Analysis of
      variance tests compared the devices. Observers repeated their sessions 1 month
      later to evaluate intraobserver reliability as measured with weighted kappa
      tests. Interclass correlation coefficients compared interobserver reliability.
      RESULTS: There was no significant difference in perceptibility detection between
      the Lenovo M92z desktop, iPad 3, and iPad mini. However, on average, all 3 were
      significantly better than the Lenovo Z580 laptop (P values <=.015). No
      significant difference in the mean absolute error was noted for working length
      measurements among the 4 viewing devices (P = .3509). CONCLUSIONS: Although all 4
      viewing devices seemed comparable with regard to working length evaluation, the
      laptop computer screen had lower overall ability to perceive contrast
      differences.

PMID- 25863406
TI  - Antibacterial and Odontogenesis Efficacy of Mineral Trioxide Aggregate Combined
      with CO2 Laser Treatment.
AB  - INTRODUCTION: Mineral trioxide aggregate (MTA) has been successfully used in
      clinical applications in endodontics. Studies show that the antibacterial effects
      of CO2 laser irradiation are highly efficient when bacteria are embedded in
      biofilm because of a photothermal mechanism. The aim of this study was to confirm
      the effects of CO2 laser irradiation on MTA with regard to both material
      characterization and cell viability. METHODS: MTA was irradiated with a dental
      CO2 laser using directly mounted fiber optics in the wound healing mode with a
      spot area of 0.25 cm(2) and then stored in an incubator at 100% relative humidity
      and 37 degrees C for 1 day to set. The human dental pulp cells cultured on MTA
      were analyzed along with their proliferation and odontogenic differentiation
      behaviors. RESULTS: The results indicate that the setting time of MTA after
      irradiation by the CO2 laser was significantly reduced to 118 minutes rather than
      the usual 143 minutes. The maximum diametral tensile strength and x-ray
      diffraction patterns were similar to those obtained without CO2 laser
      irradiation. However, the CO2 laser irradiation increased the amount of Ca and Si
      ions released from the MTA and regulated cell behavior. CO2 laser-irradiated MTA
      promoted odontogenic differentiation of hDPCs, with the increased formation of
      mineralized nodules on the substrate's surface. It also up-regulated the protein
      expression of multiple markers of odontogenic and the expression of dentin
      sialophosphoprotein protein. CONCLUSIONS: The current study provides new and
      important data about the effects of CO2 laser irradiation on MTA with regard to
      the decreased setting time and increased ion release. Taking cell functions into
      account, the Si concentration released from MTA with laser irradiation may be
      lower than a critical value, and this information could lead to the development
      of new regenerative therapies for dentin and periodontal tissue.

PMID- 25863407
TI  - Comparison between Radiographic (2-dimensional and 3-dimensional) and Histologic
      Findings of Periapical Lesions Treated with Apical Surgery.
AB  - INTRODUCTION: The aim of this study was to evaluate the concordance of 2- and 3
      dimensional radiography and histopathology in the diagnosis of periapical
      lesions. METHODS: Patients were consecutively enrolled in this study provided
      that preoperative periapical radiography (PR) and cone-beam computed tomographic
      imaging of the tooth to be treated with apical surgery were performed. The
      periapical lesional tissue was histologically analyzed by 2 blinded examiners.
      The final histologic diagnosis was compared with the radiographic assessments of
      4 blinded observers. The initial study material included 62 teeth in the same
      number of patients. RESULTS: Four lesions had to be excluded during processing,
      resulting in a final number of 58 evaluated cases (31 women and 27 men, mean age
      = 55 years). The final histologic diagnosis of the periapical lesions included 55
      granulomas (94.8%) and 3 cysts (5.2%). Histologic analysis of the tissue samples
      from the apical lesions exhibited an almost perfect agreement between the 2
      experienced investigators with an overall agreement of 94.83% (kappa = 0.8011).
      Radiographic assessment overestimated cysts by 28.4% (cone-beam computed
      tomographic imaging) and 20.7% (periapical radiography), respectively. Comparing
      the correlation of the radiographic diagnosis of 4 observers with the final
      histologic diagnosis, 2-dimensional (kappa = 0.104) and 3-dimensional imaging
      (kappa = 0.111) provided only minimum agreement. CONCLUSIONS: To establish a
      final diagnosis of an apical radiolucency, the tissue specimen should be
      evaluated histologically and specified as a granuloma (with/without epithelium)
      or a cyst. Analysis of 2-dimensional and 3-dimensional radiographic images alike
      results only in a tentative diagnosis that should be confirmed with biopsy.

PMID- 25863408
TI  - High rate of abnormal blood values and vascular complications before diagnosis of
      myeloproliferative neoplasms.
AB  - BACKGROUND: Vascular complications occurring before the diagnosis of
      myeloproliferative neoplasms (MPN) in 612 patients from four centers in Sweden,
      Denmark and France were retrospectively studied. RESULTS: Vascular complications
      were observed in 151 (25%) of the 612 patients. Of these, 66% occurred during the
      two years preceding diagnosis. The majority of events were thromboembolic (95%),
      and included myocardial infarction (n=46), ischemic stroke (n=43), transient
      ischemic attack (TIA) (n=22), deep vein thrombosis/pulmonary embolism (n=19),
      splanchnic vein thrombosis (n=7), and peripheral embolism (n=7). Bleeding was
      observed in only 7 (5%) of the 151 patients with vascular events (3 with
      intracranial bleeding, 2 with epistaxis and 2 with gastrointestinal bleeding).
      Full blood counts obtained at least 3 months prior to the MPN diagnosis showed
      that 269 (44%) had abnormal blood values, fulfilling the diagnostic criteria for
      MPN. During the time from the abnormal blood test to the diagnosis of MPN, 50
      patients suffered from a vascular complication. CONCLUSION: We therefore conclude
      that a large proportion of MPN patients suffer severe thromboembolic
      complications prior to diagnosis. If MPN were diagnosed earlier, a large
      proportion of these events might be prevented. An MPN should always be suspected
      and ruled out in patients with unexplained elevated hematocrit, leukocyte and/or
      platelet counts.

PMID- 25863409
TI  - An experience of the introduction of a blood bank automation system (Ortho
      AutoVue Innova) in a regional acute hospital.
AB  - This paper reports on an evaluation of the introduction of a blood bank
      automation system (Ortho AutoVue((r)) Innova) in a hospital blood bank by
      considering the performance and workflow as compared with manual methods. The
      turnaround time was found to be 45% faster than the manual method. The
      concordance rate was found to be 100% for both ABO/Rh(D) typing and antibody
      screening in both of the systems and there was no significant difference in
      detection sensitivity for clinically significant antibodies. The Ortho
      AutoVue((r)) Innova automated blood banking system streamlined the routine pre
      transfusion testing in hospital blood bank with high throughput, equivalent
      sensitivity and reliability as compared with conventional manual method. 

PMID- 25863410
TI  - Discriminatory power of the intraoperative cell salvage use in the prediction of
      platelet and plasma transfusion in patients undergoing cardiac surgery.
AB  - INTRODUCTION: We aim to assess the discrimination of transfused salvaged blood in
      predicting perioperative platelet and plasma transfusion. METHODS: Retrospective
      review was performed on all patients undergoing cardiac surgery with cell saver
      (CS) support. The area under the receiver operating characteristics curve was
      calculated. RESULTS: The discrimination achieved by transfused CS volumes in
      predicting perioperative platelet and plasma transfusion was poor (AUC 0.642 and
      0.613 respectively). None of the covariates included (preoperative platelets,
      cardiopulmonary bypass use and time, aortic cross clamp time and use of aspirin
      or clopidogrel within 7 days of surgery) were statistically significant
      predictors. CONCLUSION: Volumes of transfused CS blood have poor discrimination
      in predicting platelet and plasma transfusion.

PMID- 25863411
TI  - A case of pulseless electrical activity secondary to pulmonary embolism: A
      medical emergency occurring in an LDL apheresis center.

PMID- 25863412
TI  - Determination of specimen storage conditions for measuring isoagglutinin titers.
AB  - BACKGROUND: This study aimed to determine the optimal specimen storage conditions
      for isoagglutinin titration by changing storage time and temperature. STUDY
      DESIGN AND METHODS: Serum specimens from 60 individuals were stored at room
      temperature (RT, 25  degrees C) or at 4  degrees C and tested every 24 hours
      until 96 hours by the immediate spin (IS) method and the anti-human globulin
      method using dithiothreitol (DTT-AHG). These titer results were compared with the
      titers which were measured when the samples arrived. The titer endpoint was
      defined as the highest dilution, with clinically meaningful differences defined
      as more than 4-fold differences (two serial dilutions) in titer. RESULTS: Of the
      specimens stored at RT for 24, 48, 72, and 96 hours, 5%, 12%, 12%, and 12%,
      respectively, showed two-fold (one dilution) differences by the IS method, and
      8%, 8%, 8%, and 10%, respectively, showed two-fold (one dilution) differences
      with the DTT-AHG method. Of the specimens refrigerated for 24, 48, 72, and 96
      hours, 8%, 10%, 13%, and 13%, respectively, showed two-fold (one dilution
      differences) by the IS method, and 13%, 12%, 12%, and 12%, respectively, showed
      two-fold (one dilution) differences with the DTT-AHG method. CONCLUSIONS:
      Specimens stored for up to 96 hours at RT and 4  degrees C showed similar titers
      using the IS and DTT-AHG methods. These findings suggest that tests can be
      scheduled regularly.

PMID- 25863413
TI  - Autologous blood transfusion for hemodialysis patients: A case report and review
      of clinical reports and therapeutic features.
AB  - CASE REPORT: We describe a hemodialysis (HD) patient who successfully underwent
      total hip arthroplasty with autologous blood transfusion (ABT). There were
      several problems with collecting ABT in this setting. DISCUSSION: A literature
      search for HD patients and ABT produced 8 articles describing 29 patients. Higher
      doses of erythropoietin stimulating agents were used to collect ABT than for a
      typical HD session. In 75% of the cases autologous blood was collected just after
      HD to collect better quality blood. The optimal clinical procedures for ABT in HD
      patients need to be clarified.

PMID- 25863414
TI  - Penile brachytherapy-Retrospective review of a single institution.
AB  - PURPOSE: To analyze the results of exclusive brachytherapy (BT) to treat patients
      with penile squamous cell carcinoma confined to the glans or prepuce. METHODS AND
      MATERIALS: Retrospective analysis of 25 patients treated for T1-T2 penile cancer
      with exclusive interstitial BT between July 1989 and March 2014 at our
      institution. RESULTS: Median followup was 9.2 years (range, 0-19). The mean
      patient age was 65.3 years (range, 51-80). Most patients underwent exclusive low
      dose-rate BT (56%; n = 14) or pulsed-dose-rate BT (40%; n = 10). Only 1 patient
      received high-dose-rate BT (4%). The median prescribed dose was 60 Gy. Eight
      patients died during follow-up because of systemic progression (one case) and
      other intercurrent causes (seven cases). Two failures were recorded (one local
      and one regional), both at 4 months after BT. The remaining patients continued
      follow-up at our institution and maintained response. Two patients underwent
      partial phallectomy for toxicity. At the time of this report, 12 of the 25
      patients are alive and free of disease. The most common late toxicities were
      telangiectasia, urethral stenosis, and atrophy, in 48%, 43%, and 17.4% of
      patients, respectively. CONCLUSIONS: BT with low dose rate/pulsed dose rate
      provides excellent locoregional control for small (<=4 cm) T1-T2 squamous cell
      carcinoma of the penile glans.

PMID- 25863415
TI  - Phantom perception: voluntary and involuntary nonretinal vision.
AB  - Hallucinations, mental imagery, synesthesia, perceptual filling-in, and many
      illusions are conscious visual experiences without a corresponding retinal
      stimulus: what we call 'phantom perception'. Such percepts show that our
      experience of the world is not solely determined by direct sensory input. Some
      phantom percepts are voluntary, whereas others are involuntarily, occurring
      automatically. Here, by way of review, we compare and contrast these two types of
      phantom perception and their neural representations. We propose a dichotomous
      framework for phantom vision, analogous to the subtypes of attention: endogenous
      and exogenous. This framework unifies findings from different fields and species,
      providing a guide to study the constructive nature of conscious sensory
      perception. 

PMID- 25863416
TI  - Rare Incidence of Ventricular Tachycardia and Torsades de Pointes in Hospitalized
      Patients With Prolonged QT Who Later Received Levofloxacin: A Retrospective
      Study.
AB  - OBJECTIVE: To determine the incidence of ventricular tachycardia and ventricular
      fibrillation in patients with prolonged corrected QT interval (QTc) who received
      levofloxacin through retrospective chart review at a tertiary care teaching
      hospital in the United States. PATIENTS AND METHODS: We selected 1004 consecutive
      hospitalized patients with prolonged QTc (>450 ms) between October 9, 2009 and
      June 12, 2012 at our institution. Levofloxacin was administered orally and/or
      intravenously and adjusted to renal function in the inpatient setting. The
      primary outcome measure was sustained ventricular tachycardia recorded
      electrocardiographically. RESULTS: With a median time from the start of
      levofloxacin use to hospital discharge (or death) of 4 days (range, 1-94 days),
      only 2 patients (0.2%; 95% CI, 0.0%-0.7%) experienced the primary outcome of
      sustained ventricular tachycardia after the initiation of levofloxacin use.
      CONCLUSION: In this study, the short-term risk for sustained ventricular
      tachycardia in patients with a prolonged QTc who subsequently received
      levofloxacin was very rare. These results suggest that levofloxacin may be a safe
      option in patients with prolonged QTc; however, studies with longer follow-up are
      needed.

PMID- 25863417
TI  - Health-enhancing multibehavior and medical multimorbidity.
AB  - OBJECTIVE: To examine the association of multibehavior on multimorbidity.
      PATIENTS AND METHODS: Data from the 2005-2006 National Health and Nutrition
      Examination Survey were used. The study duration was from October 20, 2013,
      through December 16, 2014. A multimorbidity index variable was created that
      indicated the number of 14 morbidities that each patient had. A multibehavior
      index variable was created that indicated the number of 4 health-enhancing
      behaviors each participant had; physical activity was assessed via accelerometry,
      dietary behavior was assessed via an interview, smoking was determined via
      cotinine levels, and sleep duration was self-reported. RESULTS: For the entire
      sample of 2048 participants, those with 1, 2, 3, and 4 health behaviors, compared
      with 0 health behaviors, had a 35% (odds ratio [OR], 0.65; 95% CI, 0.47-0.90;
      P=.01), 44% (OR, 0.56; 95% CI, 0.38-0.82; P=.006), 63% (OR, 0.37; 95% CI, 0.26
      0.51; P<.001), and 69% (OR, 0.31; 95% CI, 0.19-0.52; P<.001) reduced odds of
      being multimorbid, respectively. Only physical activity (beta=-.46) and sleep
      (beta=-.23) were independently associated with multimorbidity, and only 2 health
      behavior combinations were associated with multimorbidity: physical activity and
      sleep (beta=-.17) and physical activity and nonsmoking (beta=-.16). CONCLUSIONS:
      Americans engaging in more health behaviors were less likely to be multimorbid.
      Physical activity was independently, as well is in combination with other health
      behaviors, associated with multimorbidity. Implications for developing a
      multibehavior-multimorbidity framework to treat the patients' holistic needs is
      discussed.

PMID- 25863418
TI  - Does the use of dedicated dispatch criteria by Emergency Medical Services
      optimise appropriate allocation of advanced care resources in cases of high
      severity trauma? A systematic review.
AB  - BACKGROUND AND OBJECTIVES: The deployment of Enhanced Care Teams (ECTs) capable
      of delivering advanced clinical interventions for patients at the scene of
      incidents is commonplace by Emergency Medical Services in most developed
      countries. It is unclear whether primary dispatch models for ECT resources are
      more efficient at targeting deployment to patients with severe trauma than
      secondary dispatch, following requests from EMS personnel at scene. The objective
      of this study was to review the evidence for primary and secondary models in the
      targeted dispatch of ECT resources to patients with severe traumatic injury.
      METHODS: This review was completed in accordance with a protocol developed using
      the PRISMA guidelines. We conducted a search of the MEDLINE, EmBase, Web of
      Knowledge/Science databases and the Cochrane library, focussed on subject
      headings and keywords involving the dispatch of ECT resources by Emergency
      Medical Services. Design and results of each study were described. Heterogeneity
      in the design of the included studies precluded the completion of a meta
      analysis. A narrative synthesis of the results therefore was performed. RESULTS:
      Five hundred and forty-eight articles were screened, and 16 were included. Only
      one study compared the performance of the different models of dispatch. A non
      statistically significant reduction in the length of time for HEMS resources to
      reach incident scenes of 4min was found when primary dispatch protocols were
      utilised compared to requests from EMS personnel at scene. No effect on
      mortality; severity of injury or proportion of patients admitted to intensive
      care was observed. The remaining studies examined the processes utilised within
      current primary dispatch models but did not perform any comparative analysis with
      existing secondary dispatch models. CONCLUSIONS: This review identifies a lack of
      evidence supporting the role of primary dispatch models in targeting the
      deployment of Enhanced Care Teams to patients with severe injuries. It is
      therefore not possible to identify a model for ECT dispatch within pre-hospital
      systems that optimises resource utilisation. Further studies are required to
      assess the efficiency of systems utilised at each stage of the process used to
      dispatch Enhanced Care Team resources to incidents within regionalised pre
      hospital trauma systems.

PMID- 25863419
TI  - Influence of Intravenous Nitrate Treatment on Early Mortality Among Patients With
      Acute Heart Failure. NITRO-EAHFE Study.
AB  - INTRODUCTION AND OBJECTIVES: There is little evidence on the prognostic influence
      of intravenous nitrates in patients with acute heart failure. Our purpose was to
      determine the influence of this treatment on early mortality and new visits.
      METHODS: Prospective, multicenter cohort study of patients with acute heart
      failure in an emergency room during 2 periods (May 2009 and November-December
      2011). Patients with systolic blood pressure > 110mmHg were included, grouped
      according to whether they received intravenous nitroglycerin or not. Endpoints
      were mortality at 3, 7, 14, and 30 days and new visits at 30 days. The propensity
      score was estimated by logistic regression to determine the prognostic influence
      of the treatment. RESULTS: We included 3178 of 4897 individuals. A total of 308
      (9.7%) had died within 30 days and 465 (17%) attended new visits. The mean
      (standard deviation) age was 79.5 (10.0) years, and 796 (25%) patients received
      intravenous nitrates. After matching, there were 685 individuals in each group.
      The hazard ratio for 30-day mortality with nitrates was 1.21 (95% confidence
      interval, 0.87-1.70) and was 0.93 for new visits (95% confidence interval, 0.71
      1.22). The results were similar for mortality at 3, 7, and 14 days (hazard ratio
      = 1.05 [95% confidence interval, 0.56-1.96], hazard ratio = 1.20 [95% confidence
      interval, 0.74-1.94], and hazard ratio = 1.23 [95% confidence interval, 0.82
      1.84], respectively). In the presence of hypertensive pulmonary edema, the
      nitrates group showed a hazard ratio of 0.88 (95% confidence interval, 0.47-1.63)
      for 30-day mortality. CONCLUSIONS: Intravenous nitrates do not influence early
      mortality or new visits in patients with acute heart failure.

PMID- 25863420
TI  - Comparison of Two Questionnaires for Dry Eye Symptom Assessment: The Ocular
      Surface Disease Index and the Symptom Assessment in Dry Eye.
AB  - PURPOSE: The aim of this study was to compare patient-reported symptoms of dry
      eye disease (DED) as assessed by the Ocular Surface Disease Index (OSDI), a 12
      item symptom frequency-based questionnaire, and the Symptom Assessment iN Dry Eye
      (SANDE), a 2-item frequency- and severity-based visual analog scale. DESIGN:
      Clinic-based evaluation of a diagnostic test. PARTICIPANTS: A total of 114
      patients with DED. METHODS: Patients were administered the OSDI and SANDE
      questionnaires at baseline and follow-up visits to evaluate DED-related symptoms.
      The correlations between both questionnaires' scores were evaluated using the
      Spearman coefficient, and their clinical differences were assessed using Bland
      Altman analysis. MAIN OUTCOME MEASURES: Baseline and follow-up visit OSDI and
      SANDE dry eye symptom scores. RESULTS: At the baseline visit, the OSDI and SANDE
      questionnaire scores were significantly correlated (R = 0.64; P < 0.001).
      Moreover, a significant correlation was found between changes in the OSDI and
      SANDE scores from baseline to follow-up visits (R = 0.47; P < 0.001). A Bland
      Altman analysis, after score normalization, revealed a difference (bias) of less
      than 2 centesimal units between the scores of the 2 questionnaires. CONCLUSIONS:
      Data collected from the SANDE questionnaire showed a significant correlation and
      negligible score differences with those from the OSDI, suggesting that the SANDE
      visual analog scale-based questionnaire has the potential to provide clinicians
      with a short, quick, and reliable measure for DED symptoms.

PMID- 25863421
TI  - Ruthenium-106 Plaque Brachytherapy in the Primary Management of Ocular
      Medulloepithelioma.

PMID- 25863422
TI  - Prognostic value of serial B-type natriuretic peptide measurement in
      transcatheter aortic valve replacement (from the PARTNER Trial).
AB  - B-type natriuretic peptide (BNP) levels have shown a correlation with outcomes in
      studies of aortic valve surgery. Results from multicenter trials of BNP in
      transcatheter aortic valve surgery (TAVR) are lacking. The aim of this study was
      to investigate the prognostic role of serial measurement of BNP in transfemoral
      TAVR. A total of 1,097 patients who underwent TAVR via transfemoral access were
      analyzed by tertile of baseline BNP. Of those, 933 with BNP levels at 30 days
      were divided into 2 groups on the basis of increases (334 patients) or decreases
      or no change (599 patients) in BNP compared with baseline. Patients in the low
      tertile BNP group had a lower rate of death at 1 year than those in the higher
      tertile group (15.0% vs 23.0%, p<0.01) which was not significant in multivariate
      analysis. Over 1 year, BNP decreased from 1,258.13+/-2,988.33 to 594.37+/
      1,087.30 (p<0.01) in the entire group. Patients in the BNP-rise group had higher
      rates of death at 1 year (20.3% vs 11.4%, p<0.01) and an overall increase in
      moderate or severe aortic regurgitation over 1 year (p<0.01). Multivariate
      predictors of 1-year mortality were moderate or severe aortic regurgitation
      (hazard ratio 2.04, 95% confidence interval 1.36 to 3.05, p<0.01), increase in
      BNP at 30 days (hazard ratio 1.82, 95% confidence interval 1.26 to 2.62, p<0.01)
      and Society of Thoracic Surgeons score (hazard ratio 1.05, 95% confidence
      interval 1.01 to 1.10, p=0.03). In conclusion, increase in BNP at 30 days from
      baseline and moderate or severe aortic regurgitation at 30 days in patients who
      undergo transfemoral TAVR are independently associated with 1-year mortality.
      Increase in BNP at 30 days should prompt evaluation for causes of elevated wall
      stress, including aortic regurgitation.

PMID- 25863423
TI  - Lightheadedness, fatigue, and bradycardia.

PMID- 25863424
TI  - Separating boys and girls and increasing weight? Assessing the impacts of single
      sex schools through random assignment in Seoul.
AB  - A growing body of research reports associations of school contexts with
      adolescents' weight and weight-related behaviors. One interesting, but under
      researched, dimension of school context that potentially matters for adolescents'
      weight is the gender composition. If boys and girls are separated into single-sex
      schools, they might be less concerned about physical appearance, which may result
      in increased weight. Utilizing a unique setting in Seoul, Korea where students
      are randomly assigned to single-sex and coeducational schools within school
      districts, we estimate causal effects of single-sex schools on weight and weight
      related behaviors. Our results show that students attending single-sex schools
      are more likely to be overweight, and that the effects are more pronounced for
      girls. We also find that girls in single-sex schools are less likely to engage in
      strenuous activities than their coeducational counterparts. 

PMID- 25863425
TI  - Clinical significance of assessing Her2/neu expression in gastric cancer with
      dual tumor tissue paraffin blocks.
AB  - One paraffin block is routinely used for human epidermal growth factor receptor 2
      (Her2/neu) immunohistochemistry (IHC) assessment. Here, we investigated if
      picking 2 paraffin blocks for Her2/neu evaluation on 1 slide is an economical,
      efficient, and practical method, which may reduce false negativity of Her2/neu
      IHC assessment due to intratumoral heterogeneity. A total of 251 gastric cancer
      (GC) patients were divided into a cohort using 1 tumor tissue paraffin block
      (single-block group, n = 132) and a cohort using dual tumor tissue paraffin
      blocks (dual-block group, n = 119) when evaluating Her2/neu expression status by
      IHC. In dual-block group, we combined the results from 2 different paraffin
      blocks and used the higher one as the final score. The number of IHC 1+, 2+, and
      3+ specimens in the single-block group was 31 (23.5%), 40 (30.3%), and 19
      (14.4%), respectively. The combined final IHC score in the dual-block group of
      1+, 2+, and 3+ was 26 (21.8%), 34 (28.6%), and 23 (19.3%), respectively.
      Inconsistent Her2/neu expression between blocks was found in 36 (30.3%) cases in
      the dual-block group. The pooled data in the single-block group and the dual
      block group indicated that, when using dual blocks, the Her2/neu-positive (3+)
      rate of GC was higher compared to that in the single-block group. Our results
      implied that using dual paraffin blocks to assess Her2/neu expression of GC may
      help identify more patients with Her2/neu-positive GC who could benefit from
      targeted therapy, by reducing false-negative rate of Her2 status assessment. This
      is an efficient, economical, and practical method for Her2/neu evaluation of GC. 

PMID- 25863426
TI  - Single-centred experience with levosimendan in paediatric decompensated dilated
      cardiomyopathy.
AB  - BACKGROUND: Children with dilated cardiomyopathy in advanced heart failure may
      spend a long time awaiting heart transplantation. Consequently, mechanical
      circulatory support is sometimes required as a bridge to transplantation.
      Levosimendan, a positive inotropic agent, has been reported to be safe and
      efficient for the treatment of paediatric heart failure. AIMS: To report our
      experience with levosimendan in children with decompensated dilated
      cardiomyopathy. METHODS: Paediatric patients with dilated cardiomyopathy on the
      transplant waiting list and with criteria for mechanical support were included in
      this single-centred retrospective study. Each patient received at least one 24
      hour infusion of levosimendan before mechanical circulatory support was
      considered. Biological and echocardiographic data were analysed. RESULTS: Six
      patients were included over a 24-month period. The median age was 25.5months (7.7
      34.2months); 82 infusions were performed. Median B-type natriuretic peptide
      concentration decreased significantly between days 0 and 2 (2443ng/L [1458
      3819ng/L] vs 1358ng/L [1025-2534ng/L]; P=0.003). While only a trend was noted in
      left ventricular ejection fraction improvement (P=0.054 by Simpson's method and
      P=0.068 by the Teicholz method), the subaortic velocity time integral rose
      significantly between days 0 and 8 (12.8cm/s [10-14.5cm/s] vs 15.3cm/s [14.3
      16.9cm/s]; P=0.041). CONCLUSIONS: Levosimendan seems to improve haemodynamics in
      children with decompensated dilated cardiomyopathy; repeated infusions may delay
      the need for mechanical circulatory support while awaiting heart transplantation.
      This therapeutic agent should be systematically considered in this setting, in
      addition to conventional inotropic drugs.

PMID- 25863427
TI  - A novel contribution towards coherent and reproducible intravalvular measurement
      of the aortic annulus by multidetector computed tomography ahead of transcatheter
      aortic valve implantation.
AB  - BACKGROUND: As current multidetector computed tomography (MDCT) measurements
      underestimate the size of the aortic annulus ahead of transcatheter aortic valve
      implantation (TAVI), a strategy of approximate annulus area oversizing has been
      adopted recently. AIMS: To measure the aortic annulus using a novel complementary
      intravalvular MDCT slice. METHODS: Fifty-five patients with severe aortic
      stenosis were selected for MDCT ahead of and 1 month after CoreValve((r)) TAVI.
      Two MDCT slices were analysed and compared: the current standard virtual basal
      ring (VBR) at the nadir of the aortic cusps; and a novel slice, defined as the
      basal (lowest) complete commissural coaptation (BCCC) plane. RESULTS: BCCC is an
      intravalvular plane lying 5.2+/-0.8 mm above the VBR. The BCCC annulus is almost
      circular, unlike the VBR (mean eccentricity index 0.09+/-0.04 vs 0.3+/-0.1,
      respectively). The mean BCCC annulus diameter was 26.6+/-2.3 mm, 16% larger than
      that of the VBR (23.9+/-2.2 mm; P<0.001). The BCCC annulus area proved coherent
      with the orifice area measured after TAVI on the projection of the same slice
      (i.e. systematically equal to or greater than the latter [mean difference, +2.3+/
      1.4 mm]), in contrast to the wider scatter found for the VBR (-1.3+/-2.0 mm).
      Once the sclerotic calcified valves have been pushed back by the implant, the
      aortic orifice after TAVI will inevitably be equal to or less than the diameter
      of the virtually unvalved annulus before TAVI. CONCLUSION: Based on the present
      results, we recommend including a BCCC slice to complete aortic annulus sizing,
      in order to optimize implant calibration.

PMID- 25863428
TI  - Mitral annular plane systolic excursion is an easy tool for fibrosis detection by
      late gadolinium enhancement cardiovascular magnetic resonance imaging in patients
      with hypertrophic cardiomyopathy.
AB  - BACKGROUND: Hypertrophic cardiomyopathy (HCM) causes various degrees of fibrosis
      resulting in left ventricular function impairment, which can be measured using
      mitral annular plane systolic excursion (MAPSE). AIMS: To determine the values
      for septal, lateral and average MAPSE using cardiovascular magnetic resonance
      (CMR) in healthy controls and patients with HCM; and to investigate whether MAPSE
      correlated with the extent of fibrosis. METHODS: Patients with HCM and healthy
      controls underwent CMR. RESULTS: In 50 healthy controls, septal and lateral MAPSE
      were comparable and showed excellent intra- and inter-observer reliability.
      Patients with HCM had significantly reduced septal, lateral and average MAPSE
      compared to healthy controls. Furthermore, in patients with HCM, septal MAPSE
      measurements were significantly reduced compared to lateral ones.
      Correspondingly, the septal myocardial segments showed significantly more late
      gadolinium enhancement (LGE) than lateral ones. No significant differences were
      found between echocardiographic and CMR MAPSE measurements in healthy controls
      and patients with HCM. Patients who suffered a major adverse cardiac event or
      stroke revealed a significantly reduced MAPSE and a significantly greater LGE
      extent compared to event-free patients with HCM. CONCLUSIONS: MAPSE measurement
      using CMR is feasible, reproducible and comparable to echocardiography in healthy
      controls and patients with HCM. The asymmetric and mainly septal distribution of
      myocardial hypertrophy and fibrosis detected by LGE in patients with HCM was
      reflected by significantly reduced septal versus lateral MAPSE. Therefore,
      reduced MAPSE seems to be an easily determinable marker of fibrosis accumulation
      leading to left ventricular mechanical dysfunction and also seems to have a
      prognostic implication.

PMID- 25863429
TI  - Assessment of right ventricular dysfunction predictors before the implantation of
      a left ventricular assist device in end-stage heart failure patients using
      echocardiographic measures (ARVADE): Combination of left and right ventricular
      echocardiographic variables.
AB  - BACKGROUND: Right ventricular failure (RVF) is a major cause of morbidity and
      mortality in left ventricular assist device (LVAD) recipients. OBJECTIVES: To
      identify preoperative echocardiographic predictors of post-LVAD RVF. METHODS:
      Data were collected for 42 patients undergoing LVAD implantation in Germany. RVF
      was defined as the need for placement of a temporary right ventricular assist
      device or the use of inotropic agents for 14 days. Data for RVF patients were
      compared with those for patients without RVF. A score (ARVADE) was established
      with independent predictors of RVF by rounding the exponentiated regression model
      coefficients to the nearest 0.5. RESULTS: RVF occurred in 24 of 42 LVAD patients.
      Univariate analysis identified the following measurements as RVF risk factors:
      basal right ventricular end-diastolic diameter (RVEDD), minimal inferior vena
      cava diameter, pulsed Doppler transmitral E wave (Em), Em/tissue Doppler lateral
      systolic velocity (SLAT) ratio and Em/tissue Doppler septal systolic velocity
      (SSEPT) ratio. Em/SLAT>=18.5 (relative risk [RR] 2.78, 95% confidence interval
      [CI] 1.38-5.60; P=0.001), RVEDD>=50 mm (RR 1.97, 95% CI 1.21-3.20; P=0.008) and
      INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support)
      level 1 (RR 1.74, 95% CI 1.04-2.91; P=0.04) were independent predictors of RVF.
      An ARVADE score>3 predicted the occurrence of post-implantation RVF with a
      sensitivity of 89% and a specificity of 74%. CONCLUSION: The ARVADE score,
      combining one clinical variable and three echocardiographic measurements, is
      potentially useful for selecting patients for the implantation of an assist
      device.

PMID- 25863430
TI  - Delayed bleeding due to hydatid cyst rupture one month after blunt liver trauma.

PMID- 25863431
TI  - Polybrominated diphenyl ethers with potent and broad spectrum antimicrobial
      activity from the marine sponge Dysidea.
AB  - Three polybrominated diphenyl ethers, 2-(2',4'-dibromophenoxy)-3,5-dibromophenol
      (1) and 2-(2',4'-dibromophenoxy)-3,4,5-tribromophenol (2) were isolated from the
      marine sponge Dysidea granulosa; and 2-(2',4'-dibromophenoxy)-4,6-dibromophenol
      (3) from Dysidea spp. They exhibited potent and broad spectrum in vitro
      antibacterial activity, especially against methicillin resistant Staphylococcus
      aureus (MRSA), methicillin sensitive Staphylococcus aureus (MSSA), Escherichia
      coli O157:H7, and Salmonella. Minimal inhibitory concentration (MIC) was
      evaluated against 12 clinical and standard strains of Gram positive and negative
      bacteria. The observed MIC range was 0.1-4.0mg/L against all the Gram positive
      bacteria and 0.1-16.0mg/L against Gram negative bacteria. 2-(2',4"
      Dibromophenoxy)-3,5-dibromophenol showed stronger broad spectrum antibacterial
      activity than other two compounds. 2-(2',4"-Dibromophenoxy)-3,5-dibromophenol and
      2-(2',4'-dibromophenoxy)-4,6-dibromophenol are thermo-stable. The results suggest
      that 2-(2',4'-dibromophenoxy)-3,5-dibromophenol could be used as a potential lead
      molecule for anti-MRSA, anti-E. coli O157:H7, and anti-Salmonella for drug
      development. 

PMID- 25863432
TI  - New cytochalasins from medicinal macrofungus Crodyceps taii and their inhibitory
      activities against human cancer cells.
AB  - Three new cytochalasins (1-3) together with two known cytochalasin analogues (4
      and 5) were isolated from the chloroform fraction of ethanolic extract of a
      medicinal macrofungus Cordyceps taii. The structures of the new compounds were
      elucidated on the basis of spectroscopic analysis, including HRESIMS, 1D and 2D
      NMR experiments. The cytotoxicities of Compounds 1-5 were investigated by the
      sulforhodamine B (SRB) method in vitro against human highly metastatic lung
      cancer cell 95-D, human lung cancer cell line A-549 and normal hepatocyte HL
      7702. The results revealed that Compounds 4 and 5 showed potent antitumor
      activities against human lung cancer cell 95-D with IC50 value of 3.67 and 4.04
      MUM, respectively. In comparison with cisplatin, the first-line chemotherapy
      drug, they had little or no cytotoxicity on normal cells, but showed stronger
      cytotoxic effects on cancer cells 95-D.

PMID- 25863433
TI  - Evolution and synthesis of novel orally bioavailable inhibitors of PDE10A.
AB  - The design and synthesis of highly potent, selective orally bioavailable
      inhibitors of PDE10A is reported. Starting with an active compound of modest
      potency from a small focused screen, we were able to evolve this series to a lead
      molecule with high potency and selectivity versus other PDEs using structure
      based design. A systematic refinement of ADME properties during lead optimization
      led to a lead compound with good half-life that was brain penetrant. Compound 39
      was highly potent versus PDE10A (IC50=1.0 nM), demonstrated high selectivity
      (>1000-fold) against other PDEs and was efficacious when dosed orally in a rat
      model of psychosis, PCP-induced hyperlocomotion with an EC50 of 1 mg/kg.

PMID- 25863434
TI  - Quantifying motivational deficits and apathy: a review of the literature.
AB  - Varying definitions of apathy in the published literature and a lack of a
      consensus regarding diagnostic criteria make the identification and
      quantification of apathy difficult in both clinical trials and clinical practice.
      The Apathy Evaluation Scale was developed specifically to assess apathy, but
      variations in the threshold values defined for clinically significant apathy
      diminish its use as a screening tool in clinical trials, although it has
      demonstrated sensitivity to changes in treatment in a number of studies. The
      Neuropsychiatric Inventory contains an Apathy subscale, which has been used to
      identify clinical trial populations (with a consistent threshold value) and
      measure changes following treatment. Few of the other assessment tools currently
      used in patients with neuropsychiatric disorders are specific for apathy or
      explore it in any depth, most have not been validated in the general population,
      do not have cut-off points representing clinically significant apathy, and its
      changes over time and in response to treatment. Further research is required to
      address these issues in order to facilitate the quantification of apathy and its
      natural history. Such research should be conducted with the aim of developing
      new, specific tools for use across neuropsychiatric disorders. 

PMID- 25863435
TI  - Perioperative factors that influence the outcome of microsurgical reconstructions
      in craniomaxillofacial surgery.
AB  - Microsurgical tissue transfer is a well-established way of reconstructing the
      head and neck, but there are still many postoperative complications that require
      revision. The aim of this study was to clarify perioperative factors and
      characteristics of patients that influence the success of the flap and the need
      for revision. We retrospectively studied 368 patients who were treated with
      microsurgical free tissue transfer in the head and neck area at the Department of
      Oral and Maxillofacial Surgery at the University Medical Centre, Erlangen,
      between 2004 and 2009. Investigations concentrated on patients' characteristics
      and operative factors. Free scapular or parascapular flaps (n=161, 44%) and
      radial forearm flaps (n=119, 32%) were predominantly used for the reconstruction
      of major defects in the mandible and the floor of the mouth. In 39 patients (11%)
      revision was required, which resulted in a success rate of 96%. There was a
      significant association between preoperative American Society of
      Anesthesiologists (ASA) grade and postoperative survival of the flap (p=0.04).
      Patients previously treated by irradiation required significantly more revisions
      than those not so treated (p=0.04). The use of vein grafts was also significantly
      associated with the need for revision (p=0.02). The ASA grade influenced the
      success rate but was not associated with the number of revisions. These factors
      must be taken into consideration when intervention is planned to reduce the
      number of postoperative complications and interventions further. 

PMID- 25863436
TI  - Postmortem redistribution of the heroin metabolites morphine and morphine-3
      glucuronide in rabbits over 24 h.
AB  - The interpretation of postmortem drug levels is complicated by changes in drug
      blood levels in the postmortem period, a phenomena known as postmortem drug
      redistribution. We investigated the postmortem redistribution of the heroin
      metabolites morphine and morphine-3-glucuronide in a rabbit model. Heroin (1
      mg/kg) was injected into anesthetised rabbit; after 1 h, an auricular vein blood
      sample was taken and the rabbit was euthanised. Following death rabbits were
      placed in a supine position at room temperature and divided into three groups
      namely (1) immediate autopsy, (2) autopsy after 30 minutes and (3) autopsy 24 h
      after death. Various samples which included femoral blood, cardiac blood, lung,
      liver, kidney, vitreous humour, subcutaneous and abdominal fat, liver, bone
      marrow and skeletal muscle were taken. The samples were analysed with a validated
      LC-MS/MS method. It was observed that within minutes there was a significant
      increase in free morphine postmortem femoral blood concentration compared to the
      antemortem sample (0.01 +/- 0.01 to 0.05 +/- 0.02 mg/L).Various other changes in
      free morphine and metabolite concentrations were observed during the course of
      the experiment in various tissues. Principal component analysis was used to
      investigate possible correlations between free morphine in the various samples.
      Some correlations were observed but gave poor predictions (>20 % error) when back
      calculating. The results suggest that rabbits are a good model for further
      studies of postmortem redistribution but that further study and understanding of
      the phenomena is required before accurate predictions of the blood concentration
      at the time of death are possible.

PMID- 25863437
TI  - Construction of a photocatalytic de-polluting field site in the Leopold II tunnel
      in Brussels.
AB  - Within the framework of the European Life+-funded project PhotoPAQ (Demonstration
      of Photocatalytic remediation Processes on Air Quality), which was aimed at
      demonstrating the effectiveness of photocatalytic coating materials on a
      realistic scale, a photocatalytic de-polluting field site was set up in the
      Leopold II tunnel in Brussels, Belgium. For that purpose, photocatalytic
      cementitious materials were applied on the side walls and ceiling of selected
      test sections inside a one-way tunnel tube. This article presents the
      configuration of the test sections used and the preparation and implementation of
      the measuring campaigns inside the Leopold II tunnel. While emphasizing on how to
      implement measuring campaigns under such conditions, difficulties encountered
      during these extensive field campaigns are presented and discussed. This included
      the severe de-activation observed for the investigated material under the
      polluted tunnel conditions, which was revealed by additional laboratory
      experiments on photocatalytic samples that were exposed to tunnel air. Finally,
      recommendations for future applications of photocatalytic building materials
      inside tunnels are given. 

PMID- 25863438
TI  - Imaging of Tumor Angiogenesis for Radiologists--Part 2: Clinical Utility.
AB  - Angiogenesis is a key cancer hallmark involved in tumor growth and metastasis
      development. Angiogenesis and tumor microenvironment significantly influence the
      response of tumors to therapies. Imaging techniques have changed our
      understanding of the process of angiogenesis, the resulting vascular performance,
      and the tumor microenvironment. This article reviews the status and potential
      clinical value of the imaging modalities used to assess the status of tumor
      vasculature in vivo, before, during, and after treatment. 

PMID- 25863439
TI  - Alternation of light/dark period priming enhances clomazone tolerance by
      increasing the levels of ascorbate and phenolic compounds and ROS detoxification
      in tobacco (Nicotiana tabacum L.) plantlets.
AB  - The effect of the alternation of light/dark periods (AL) (16/8 min light/dark
      cycles and a photosynthetic photon flux density (PPFD) of 50 MUmol photons m(-2)
      s(-1) for three days) to clarify the mechanisms involved in the clomazone
      tolerance of tobacco plantlets primed with AL was studied. Clomazone decreased
      PSII activity, the net photosynthetic rate (Pn), and the ascorbate and total
      polyphenol contents and increased H2O2 and starch grain accumulation and the
      number of the cells that underwent programmed cell death (PCD). The pretreatment
      with AL reduced the inhibitory effect of clomazone on the PSII activity and
      photosynthesis, as indicated by the decreases in the H2O2 and starch grain
      accumulation and the PCD levels, and increased the content of ascorbate and
      certain phenolic compounds, such as chlorogenic acid, neochlorogenic acid and
      rutin. The AL treatment could promote photorespiration via post-illumination
      burst (PIB) effects. This alternative photorespiratory electron pathway may
      reduce H2O2 generation via the consumption of photochemical energy, such as
      NADH+H(+). At 10 days (D10) of AL treatment, this process induced moderate stress
      which stimulates H2O2 detoxification systems by increasing the activity of
      antioxidant enzymes and the biosynthesis of antioxidant components. Therefore,
      the PCD levels provoked by clomazone were noticeably decreased.

PMID- 25863440
TI  - Realizing the recognition features of model antipsychotic compounds by important
      protein: Photochemical and computational studies.
AB  - Phenothiazine and its derivatives are the most effective antipsychotic drugs.
      They have been used in the treatment of serious mental and emotional symptoms
      including bipolar disorder, organic psychoses, psychotic depression and
      schizophrenia. However, these drugs cause serious side effects such as akathisia,
      hyperprolactinaemia and neuroleptic malignant syndrome. In this work we
      investigated the molecular recognition of two typical phenothiazine compounds,
      phenosafranin and safranin O by the most pivotal heme protein hemoglobin using
      steady state and time-resolved fluorescence, extrinsic 8-anilino-1
      naphthalenesulfonic acid (ANS) fluorescent probe, circular dichroism (CD) along
      with computational modeling. Results show phenothiazines complex with protein via
      formation of adducts at 298 K with moderate strengths of 3.555*10(4) M(-1) and
      2.567*10(4) M(-1) for the hemoglobin-phenosafranin and hemoglobin-safranin O,
      respectively. We also found phenothiazines were effectors at the protein
      allosteric site, which affects the allosteric equilibrium. Further, time-resolved
      fluorescence and hydrophobic ANS experiments showed the static mechanism is
      dominated for the shrinkage in the fluorescence intensity of beta-37 Trp residue
      at the alpha1beta2 interface. The stoichiometric proportion of the protein-drug
      adduct is 1:1, as derived from Job's plot. Several crucial noncovalent bonds,
      including hydrogen bonds, pi-pi stacking and hydrophobic interactions played a
      major role in stabilizing the noncovalent conjugates. Based on three-dimensional
      fluorescence, we concluded that the conformation of hemoglobin is partially
      destabilized after recognition with phenothiazines. These alterations were
      confirmed by far-UV CD spectra that showed the alpha-helix of protein decreased
      from 78.3% in free hemoglobin to 62.8% and 64.8% in hemoglobin-phenosafranin and
      hemoglobin-safranin O, respectively. Computer-aided molecular docking was
      consistent, indicating that both phenothiazines are situated within the pocket
      composed of alpha1 and beta2 subunits. Affinity of hemoglobin to phenosafranin is
      superior compared with safranin O. This difference may be explained by the methyl
      group substituent on A- and C-rings, and by the different molecular volume
      between phenosafranin and safranin O. Our data provides further explanation of
      the overall pharmacokinetics of phenothiazines and sheds light on the allosteric
      regulation of heme proteins.

PMID- 25863441
TI  - Arsenic trioxide binding to serum proteins.
AB  - Arsenic trioxide (ATO) also known as Trisenox, is an anticancer chemotherapeutic
      drug which has been used in treating diagnosed and relapsed patients with acute
      promyelocytic leukemia (APL). Serum albumin is the most abundant of the proteins
      in blood plasma and is the major transporter for delivering several drugs in
      vivo. The current study was designed to evaluate the potential ability of human
      and bovine serum albumin for delivering arsenic trioxide. Therefore, interaction
      of arsenic trioxide with HSA and BSA was investigated in aqueous solution at
      physiological conditions using a constant protein concentration and various drug
      contents. FTIR and UV-Vis spectroscopic methods were used to analyze arsenic
      trioxide and protein binding modes, the binding constants and the effect of drug
      complexation on HSA and BSA stability and conformation. Results of this study
      showed that drug complexation altered protein conformation by major reduction of
      alpha-helix and increase of turn structure which is indicative of a partial
      protein destabilization. Structural analysis revealed that arsenic trioxide bind
      HSA and BSA with overall binding constants of KATO-HSA=1.07 (+/-0.01)*10(4) M(-1)
      and KATO-BSA=1.27(+/-0.02)*10(4) M(-1). It could be concluded that serum albumins
      can be considered as good carriers for delivering arsenic trioxide to target
      tissue.

PMID- 25863442
TI  - Polysialic acid modification of the synaptic cell adhesion molecule SynCAM 1 in
      human embryonic stem cell-derived oligodendrocyte precursor cells.
AB  - Oligodendrocyte precursor cells (OPCs) are the progenitors of myelinating
      oligodendrocytes in brain development and repair. Successful myelination depends
      on the control of adhesiveness during OPC migration and axon contact formation.
      The decoration of cell surface proteins with the glycan polysialic acid (polySia)
      is a key regulatory element of OPC interactions during development and under
      pathological conditions. By far the major protein carrier of polySia is the
      neural cell adhesion molecule NCAM, but recently, polysialylation of the synaptic
      cell adhesion molecule SynCAM 1 has been detected in the developing mouse brain.
      In mice, polySia-SynCAM 1 is associated with cells expressing NG2, a marker of a
      heterogeneous precursor cell population, which is the primary source for
      oligodendrocytes in development and myelin repair but can also give rise to
      astrocytes and possibly neurons. It is not yet clear if polySia-SynCAM 1 is
      expressed by OPCs and its occurrence in humans is elusive. By generating uniform
      human embryonic stem cell-derived OPC cultures, we demonstrate that polySia is
      present on human OPCs but down-regulated during differentiation into myelin basic
      protein-positive oligodendrocytes. PolySia on NCAM resides on the isoforms NCAM
      180 and NCAM-140, and SynCAM 1 is identified as a novel polySia acceptor in human
      OPCs. 

PMID- 25863444
TI  - Regulation of mesenchymal stromal cells through fine tuning of canonical Wnt
      signaling.
AB  - Mesenchymal stromal cells (MSCs) have been extensively utilized for various cell
      therapeutic trials, but the signals regulating their stromal function remain
      largely unclear. Here, we show that canonical Wnt signals distinctively regulate
      MSCs in a biphasic manner depending on signal intensity, i.e., MSCs exhibit
      proliferation and progenitor self-renewal under low Wnt/beta-catenin signaling,
      whereas they exhibit enhanced osteogenic differentiation with priming to
      osteoblast-like lineages under high Wnt/beta-catenin signaling. Moreover, low or
      high levels of beta-catenin in MSCs distinctly regulated the hematopoietic
      support of MSCs to promote proliferation or the undifferentiated state of
      hematopoietic progenitors, respectively. A gene expression study demonstrated
      that different intracellular levels of beta-catenin in MSCs induce distinct
      transcriptomic changes in subsets of genes belonging to different gene function
      categories. Different beta-catenin levels also induced differences in
      intracellular levels of the beta-catenin co-factors, Tcf-1 and Lef-1. Moreover,
      nano-scale mass spectrometry of proteins that co-precipitated with beta-catenin
      revealed distinctive spectra of proteins selectively interacting with beta
      catenin at specific expression levels. Together, these results show that Wnt/beta
      catenin signals can coax distinct transcription milieu to induce different
      transcription profiles in MSCs depending on the signal intensity and that fine
      tuning of the canonical Wnt signaling intensity can regulate the phase-specific
      functionality of MSCs. 

PMID- 25863443
TI  - Assessing reproductive toxicity of two environmental toxicants with a novel in
      vitro human spermatogenic model.
AB  - Environmental influences and insults by reproductive toxicant exposure can lead
      to impaired spermatogenesis or infertility. Understanding how toxicants disrupt
      spermatogenesis is critical for determining how environmental factors contribute
      to impaired fertility. While current animal models are available, understanding
      of the reproductive toxic effects on human fertility requires a more robust model
      system. We recently demonstrated that human pluripotent stem cells can
      differentiate into spermatogonial stem cells/spermatogonia, primary and secondary
      spermatocytes, and haploid spermatids; a model that mimics many aspects of human
      spermatogenesis. Here, using this model system, we examine the effects of 2
      bromopropane (2-BP) and 1,2,dibromo-3-chloropropane (DBCP) on in vitro human
      spermatogenesis. 2-BP and DBCP are non-endocrine disrupting toxicants that are
      known to impact male fertility. We show that acute treatment with either 2-BP or
      DBCP induces a reduction in germ cell viability through apoptosis. 2-BP and DBCP
      affect viability of different cell populations as 2-BP primarily reduces
      spermatocyte viability, whereas DBCP exerts a much greater effect on
      spermatogonia. Acute treatment with 2-BP or DBCP also reduces the percentage of
      haploid spermatids. Both 2-BP and DBCP induce reactive oxygen species (ROS)
      formation leading to an oxidized cellular environment. Taken together, these
      results suggest that acute exposure with 2-BP or DBCP causes human germ cell
      death in vitro by inducing ROS formation. This system represents a unique
      platform for assessing human reproductive toxicity potential of various
      environmental toxicants in a rapid, efficient, and unbiased format. 

PMID- 25863445
TI  - The effect of estrogen synthesis inhibition on hippocampal memory.
AB  - 17-Beta-estradiol (E2) facilitates long term-potentiation (LTP) and increases
      spine synapse density in hippocampal neurons of ovariectomized rodents.
      Consistent with these beneficial effects on the cellular level, E2 improves
      hippocampus-dependent memory. A prominent approach to study E2 effects in rodents
      is the inhibition of its synthesis by letrozole, which reduces LTPs and spine
      synapse density. In the current longitudinal functional magnetic resonance
      imaging (fMRI) study, we translated this approach to humans and compared the
      impact of E2 synthesis inhibition on memory performance and hippocampal activity
      in post-menopausal women taking letrozole (n = 21) to controls (n = 24). In
      particular, we employed various behavioral memory paradigms that allow the
      disentanglement of hippocampus-dependent and -independent memory. Consistent with
      the literature on rodents, E2 synthesis inhibition specifically impaired
      hippocampus-dependent memory, however, this did not apply to the same degree to
      all of the employed paradigms. On the neuronal level, E2 depletion tended to
      decrease hippocampal activity during encoding, whereas it increased activity in
      the anterior cingulate and the dorsolateral prefrontal cortex. We thus infer that
      the inhibition of E2 synthesis specifically impairs hippocampal functioning in
      humans, whereas the increased prefrontal activity presumably reflects a
      compensatory mechanism, which is already known from studies on cognitive aging
      and Alzheimer's disease.

PMID- 25863446
TI  - Polar modified post-cross-linked resin and its adsorption toward salicylic acid
      from aqueous solution: Equilibrium, kinetics and breakthrough studies.
AB  - A novel polar modified post-cross-linked resin PDMPA was synthesized,
      characterized and evaluated for adsorption of salicylic acid from aqueous
      solution. PDMPA was prepared by a suspension polymerization of methyl acrylate
      (MA) and divinylbenzene (DVB), a Friedel-Crafts reaction and an amination
      reaction. After characterization of the chemical and pore structure of PDMPA, the
      adsorption behaviors of salicylic acid on PDMPA were determined in comparison
      with the precursor resins. The equilibrium adsorption capacity of salicylic acid
      on PDMPA was much larger than the precursor resins and the equilibrium data were
      correlated by both of the Langmuir and Freundlich models. The pseudo-second-order
      rate equation fitted the kinetic data better than the pseudo-first-order rate
      equation, and the micropore diffusion model could characterize the kinetic data
      very well. The dynamic experimental results showed that the breakthrough point
      and saturated point of salicylic acid on PDMPA were 40.3 and 92.4BV (1BV=10mL) at
      a feed concentration of 995.8mg/L and a flow rate of 1.4mL/min, and the resin
      column could be regenerated by 16.0BV of a mixture desorption solvent containing
      0.01mol/L of NaOH (w/v) and 50% of ethanol (v/v). 

PMID- 25863447
TI  - The removal of lead ions from aqueous solution by using magnetic hydroxypropyl
      chitosan/oxidized multiwalled carbon nanotubes composites.
AB  - Magnetic hydroxypropyl chitosan/oxidized multiwalled carbon nanotubes
      (MHC/OMCNTs) composites were fabricated and applied as the adsorbent to study the
      adsorption characteristic of lead ions in aqueous solution. The results of
      Fourier transform infrared spectrum (FTIR), X-ray powder diffraction (XRD) and
      scanning electron microscope (SEM) showed that the MHC/OMCNTs composites were
      synthesized successfully. The effects of the solution pH and the contact time
      were investigated, indicating that the optimal pH and contact time were pH 5.0
      and 120min, respectively. The removal of lead ions was rather quick and the
      kinetic adsorption can be well described by pseudo-second-order model. The
      experimental results showed that the Sips model is more suitable than Langmuir,
      Freundlich and Dubinin-Radushkevich models. Furthermore, the parameters of the
      adsorption thermodynamic calculated in this research such as free energy (DeltaG,
      -2.304 to -5.078kJmol(-1)), enthalpy (DeltaH, 39.03kJmol(-1)) and entropy
      (DeltaS, 138.7Jmol(-1)K(-1)) indicated that the adsorption process was
      endothermic and spontaneous. Therefore, the results in this research suggest that
      the MHC/OMCNTs composites are ideal adsorbent for the removal of lead ions in
      aqueous solution. 

PMID- 25863448
TI  - Urban-rural differences in the prevalence of allergen sensitization and self
      reported rhinitis in the elderly population.
AB  - BACKGROUND: Urbanization is frequently associated with allergic conditions during
      childhood; however, the literature lacks studies on the association between
      allergies and degree of urbanization in the elderly population. OBJECTIVE: To
      determine how the degree of urbanization affects the prevalence of allergic
      sensitization and self-reported rhinitis symptoms in elderly community
      populations. METHODS: The study population consisted of 1,311 elderly subjects
      identified from 2 community population cohort datasets who were divided into 3
      groups according to the degree of urbanization (urban, semirural, and rural)
      where they resided. Current rhinitis symptoms were assessed using a
      questionnaire. Sensitization to inhalant allergen was measured using skin prick
      tests for 9 common allergens. RESULTS: Sensitization to inhalant allergen showed
      a positive correlation with degree of urbanization (urban 17.2%, semirural 9.8%,
      rural 6.0%; P for trend <.001), with a significant correlation observed between
      house dust mite allergens and degree of urbanization. Self-reported rhinitis
      symptoms were mostly nonallergic, but showed a positive correlation with degree
      of urbanization (urban 26.8%, semirural 18.2%, rural 11.5%; P for trend <.001).
      Self-reported rhinoconjunctivitis also correlated with urbanization. Correlations
      between self-reported allergic conditions and urbanization remained statistically
      significant in multivariate logistic regression tests. CONCLUSION: The present
      analyses found significant correlations between degree of urbanization with self
      reported rhinitis symptoms and sensitization to inhalant allergen in the elderly
      population. These findings warrant further investigation of the roles that urban
      factors play in the development of elderly rhinitis and allergen sensitization.

PMID- 25863449
TI  - Novel antigens of Mycobacterium immunogenum relevant in serodiagnosis of
      occupational hypersensitivity pneumonitis in machinists.

PMID- 25863450
TI  - What is the factor that improves adherence to allergen-specific immunotherapy? A
      secretary!

PMID- 25863451
TI  - A case of isolated sudden onset Dysphagia.

PMID- 25863452
TI  - The Ear-Brain Connection: Older Ears and Older Brains.
AB  - PURPOSE: The purpose of this article is to review recent research from our
      laboratory on the topic of aging, and the ear-brain system, as it relates to
      hearing aid use and auditory rehabilitation. The material described here was
      presented as part of the forum on the brain and hearing aids, at the 2014 HEaling
      Across the Lifespan (HEAL) conference. METHOD: The method involves a narrative
      review of previously reported electroencephalography (EEG) and
      magnetoencephalography (MEG) data from our laboratory as they relate to the (a)
      neural detection of amplified sound and (b) ability to learn new sound contrasts.
      CONCLUSIONS: Results from our studies add to the mounting evidence that there are
      central effects of biological aging as well as peripheral pathology that affect a
      person's neural detection and use of sound. What is more, these biological
      effects can be seen as early as middle age. The accruing evidence has
      implications for hearing aid use because effective communication relies not only
      on sufficient detection of sound but also on the individual's ability to learn to
      make use of these sounds in ever-changing listening environments.

PMID- 25863453
TI  - The crystallization and structure features of barium-iron phosphate glasses.
AB  - The crystallization and structure features of xBaO.(90-x)(60P2O5-40Fe2O3).10CaF2
      glasses, where x=0, 5, 10, 15 and 20 mol%, are investigated in details by using X
      ray diffraction analysis, Fourier transform infrared spectroscopy, Raman
      spectroscopy and differential thermal analysis. It is found that the major
      crystalline phase of barium iron phosphate glasses annealed between 650  degrees
      C and 850  degrees C is FePO4, and the crystallization is restrained by barium.
      The predominant infrared absorption band is attributed to the antisymmetric
      stretching vibrations of (PO3)(2-) in Q(1) units. Raman and Fourier transform
      infrared spectra reveal that the glasses' main structural networks are Q(1) and
      Q(0) tetrahedrons connected by P-O-P linkages. Moreover, the glass transition
      temperature increases with BaO content, which suggests that barium can strengthen
      the thermal stability of the iron phosphate glass.

PMID- 25863454
TI  - Highly selective and sensitive fluorescence chemosensor for the detection of
      palladium species based on Tsuji-Trost reaction.
AB  - A new chemosensor 7-nitro-2,1,3-benzoxadiazole-4-allyl-N-(thiophen-2
      ylmethyl)carbamate (NBDTC) was synthesized and utilized for palladium detection
      based on the Tsuji-Trost reaction. NBDTC displayed specific and ratiometric
      fluorescent responses toward palladium species. The chemosensor showed more than
      50-fold enhancement in fluorescence intensity with the presence of PEG400 and
      palladium because NBDTC can be transformed to NBDT under palladium-catalyzing
      Tsuji-Trost reaction. NBDTC displayed high selectivity and sensitivity for
      palladium species with the detection limit of 1.13*10(-9) M.

PMID- 25863455
TI  - Guanidine-phosphate non-covalent interaction in LAP crystal growth solution
      evidenced from spectroscopy studies.
AB  - The similar L-arginine molecule aggregation has been found in L-arginine (LA) and
      L-arginine phosphate monohydrate (LAP) aqueous solutions. The special
      fluorescence emission at 380 nm of LA aggregates in LAP solution has been found,
      compared with the emission of LA solution at 415 nm, which has an obvious blue
      shift. By comparing the fluorescence spectra of several solutions for L-arginine
      and L-lysine salts, the interaction between phosphate and guanidine in LAP
      solution was considered to be the cause of its special fluorescence emission.
      Meanwhile, when LAP molecule formed in solution, the fluorescence emission
      wavelength and the UV absorption intensity at 296 nm of L-arginine solutions have
      mutated. Therefore, the group interaction involved by guanidine has changed the
      fluorescence properties of L-arginine aggregates in LAP solution, indicating that
      the specific interaction between phosphate and guanidine exists in LAP molecule.

PMID- 25863456
TI  - Infrared spectrum, NBO, HOMO-LUMO, MEP and molecular docking studies (2E)-3-(3
      nitrophenyl)-1-[4-piperidin-1-yl]prop-2-en-1-one.
AB  - FT-IR spectrum of (2E)-3-(3-nitrophenyl)-1-[4-piperidin-1-yl]prop-2-en-1-one was
      recorded and analyzed. The vibrational wavenumbers were computed using HF and DFT
      quantum chemical calculations. The data obtained from wavenumber calculations are
      used to assign IR bands. Potential energy distribution was done using GAR2PED
      software. The geometrical parameters of the title compound are in agreement with
      the XRD results. NBO analysis, HOMO-LUMO, first and second hyperpolarizability
      and molecular electrostatic potential results are also reported. The possible
      electrophile attacking sites of the title molecule is identified using MEP
      surface plot study. Molecular docking results predicted the anti-leishmanic
      activity for the compound. 

PMID- 25863457
TI  - FT-IR, NBO, HOMO-LUMO, MEP analysis and molecular docking study of Methyl N-({[2
      (2-methoxyacetamido)-4-(phenylsulfanyl)phenyl]amino}[(methoxycarbonyl)
      imino]methyl)carbamate.
AB  - The optimized molecular structure, vibrational frequencies, corresponding
      vibrational assignments of Methyl N-({[2-(2-methoxyacetamido)-4-(phenylsulfanyl)
      phenyl]amino} [(methoxycarbonyl)imino]methyl)carbamate have been investigated
      using HF and DFT levels of calculations. The geometrical parameters are in
      agreement with XRD data. The stability of the molecule arising from hyper
      conjugative interaction and charge delocalization has been analyzed using NBO
      analysis. The HOMO and LUMO analysis is used to determine the charge transfer
      within the molecule. Molecular electrostatic potential study was also performed.
      The first and second hyperpolarizability was calculated in order to find its role
      in nonlinear optics. Molecular docking studies are also reported. Prediction of
      Activity Spectra analysis of the title compound predicts anthelmintic and
      antiparasitic activity as the most probable activity with Pa (probability to be
      active) value of 0.808 and 0.797, respectively. Molecular docking studies show
      that both the phenyl groups and the carbonyl oxygens of the molecule are crucial
      for bonding and these results draw us to the conclusion that the compound might
      exhibit pteridine reductase inhibitory activity. 

PMID- 25863458
TI  - Investigations on spectroscopic properties of Er(3+)-doped Li-Zn fluoroborate
      glass.
AB  - Er(3+)-doped Li-Zn fluoroborate glass was synthesized via melt quenching
      technique. Optical properties of the glass were investigated by UV-Vis-NIR
      absorption and emission spectra. To evaluate the nature of Er(3+)-ligand bond in
      the glass network, nephelauxetic ratios and bonding parameter were calculated.
      Judd-Ofelt analysis and hence the radiative properties of the present glass
      system were evaluated for ascertaining the suitability of the glass for laser
      applications and compared those with the emission spectra. Absorption cross
      sections have been calculated from the absorption spectrum and stimulated
      emission cross-sections were estimated using McCumber theory for (4)I13/2<
      >(4)I15/2 transitions. The results of the present glass were compared with those
      obtained for some other Er(3+)-doped glass systems. 

PMID- 25863459
TI  - Interaction of quinine sulfate with anionic micelles of sodium dodecylsulfate: A
      time-resolved fluorescence spectroscopy at different pH.
AB  - Photophysical behavior and rotational relaxation dynamics of quinine sulfate (QS)
      in anionic surfactant, sodium dodecylsulfate (SDS) at different pH have been
      studied using steady state and time resolved fluorescence spectroscopy. It has
      been observed that the cationic form of quinine sulfate (at pH 2) forms a
      fluorescent ion pair complex with the surfactant molecules at lower
      concentrations of surfactant. However, for higher concentrations of SDS, the
      probe molecules bind strongly with the micelles and reside at the water-micelle
      interface. At pH 7, QS is singly protonated in bulk aqueous solution. At lower
      concentrations of SDS aggregation between probe and surfactant molecules has been
      observed. However, for higher concentrations of SDS, an additional fluorescence
      peak corresponding to dicationic form of QS appears and this has been attributed
      to double protonation of the QS molecule in micellar solution. At pH 7, in the
      presence of SDS micelles, the photophysical properties of QS showed substantial
      changes compared to that in the bulk water solution. At pH 12, an increase in
      fluorescence intensity and lifetime has been observed and this has been
      attributed to the increase in radiative rate due to the incorporation of QS at
      the micelle-water interface. The local pH at micellar surface has been found
      different from the pH of bulk solution. 

PMID- 25863460
TI  - Excited states and absorption spectra of 2-beta-diketonato-1,3,2-benzodioxaborol
      with aromatic substituents: Quantum-chemistry modeling.
AB  - The nature of excited states of 2-beta-diketonato-1,3,2-benzodioxaborol compounds
      with aromatic substituent have been studied by the quantum-chemical method in the
      approximation of the time-dependent electron density functional theory. We have
      measured the absorption spectra of these compounds in acetonitrile solution and
      compared them with the model spectra constructed on the basis of calculations.
      The calculations give two long-wavelength transitions with small oscillator
      strengths, caused by pi-pi transitions with the charge transfer from the
      benzodioxo-group to the chelate fragment. Observed long-wavelength shoulders of
      the spectra bands correlate with the mentioned transitions. Typical high
      intensity bands for pi-pi transitions in the ultra-violet range are caused by
      transitions of pi-electrons in the fragments. Increasing extension of pi-system
      gives the batochromic shift of these absorption bands and the growth of the
      probabilities of the transition. 

PMID- 25863461
TI  - Derivative spectrophotometric method for simultaneous determination of zofenopril
      and fluvastatin in mixtures and pharmaceutical dosage forms.
AB  - Fast, accurate and precise method for the determination of zofenopril and
      fluvastatin was developed using spectrophotometry of the first (D1), second (D2),
      and third (D3) order derivatives in two-component mixtures and in pharmaceutical
      preparations. It was shown, that the developed method allows for the
      determination of the tested components in a direct manner, despite the apparent
      interference of the absorption spectra in the UV range. For quantitative
      determinations, "zero-crossing" method was chosen, appropriate wavelengths for
      zofenopril were: D1 lambda=270.85 nm, D2 lambda=286.38 nm, D3 lambda=253.90 nm.
      Fluvastatin was determined at wavelengths: D1 lambda=339.03 nm, D2 lambda=252.57
      nm, D3 lambda=258.50 nm, respectively. The method was characterized by high
      sensitivity and accuracy, for zofenopril LOD was in the range of 0.19-0.87 MUg
      mL(-1), for fluvastatin 0.51-1.18 MUg mL(-1), depending on the class of
      derivative, and for zofenopril and fluvastatin LOQ was 0.57-2.64 MUg mL(-1) and
      1.56-3.57 MUg mL(-1), respectively. The recovery of individual components was
      within the range of 100+/-5%. For zofenopril, the linearity range was estimated
      between 7.65 MUg mL(-1) and 22.94 MUg mL(-1), and for fluvastatin between 5.60
      MUg mL(-1) and 28.00 MUg mL(-1).

PMID- 25863462
TI  - Comparison of ultrasound-assisted cloud point extraction and ultrasound-assisted
      dispersive liquid liquid microextraction for copper coupled with
      spectrophotometric determination.
AB  - In this work, ultrasound-assisted cloud point extraction (UA-CPE) and ultrasound
      assisted dispersive liquid liquid microextraction (UA-DLLME) were investigated
      and compared firstly as ultrasound-assisted liquid phase microextraction methods,
      which were coupled with spectrophotometer for copper preconcentration and
      detection. Compared to conventional CPE and DLLME, the extraction patterns were
      changed and improved by the effect of ultrasound. As novel methods, their
      applications were expanded and the analytical performance of spectrophotometric
      determination for copper was considerably improved. The influence factors of UA
      CPE and UA-DLLME were studied in detail. Under the optimal conditions, the limits
      of detection (LODs) for copper were 0.7 MUg L(-1) of UA-CPE and 0.8 MUg L(-1) of
      UA-DLLME with sensitivity enhancement factors (EFs) of 17 and 16. The developed
      methods were applied to the determination of trace copper in real water samples
      with satisfactory analytical results.

PMID- 25863463
TI  - [Patient counseling in case of postoperative complication leading to emergency
      reintervention in plastic surgery. What is the current situation? How to improve?
      Retrospective study of counseling modalities and traceability in a series of 16
      patients who needed emergency reintervention within a cohort of 402 patients].
AB  - AIM: Preoperative counseling is structured and well defined. Nevertheless, in the
      event of a complication leading to a new emergency surgical procedure, counseling
      is not well defined. We conducted a retrospective study of information delivered
      in this situation at our institution. PATIENTS AND METHODS: We included all the
      patients who underwent emergency reintervention because of hematoma or operative
      site infection between November 2013 and October 2014. Sixteen patients were
      included over the 402 patients operated during this period. RESULTS: Information
      before initial surgery: all patients had at least two preoperative consultations,
      and all preoperative informed consents were obtained. Complications leading to
      reintervention were mentioned in the consultation record in 31% of cases, and in
      a letter to another practitioner in 19% of cases. SofCPRE information card was
      delivered in 63% of cases. Information before reintervention: reintervention
      indication was mentioned in the hospitalization report in 81% of cases, and in
      the operative report in 88% of cases. Blood count results were mentioned in 55%
      of cases when it had been done. Patients were orally informed of reintervention
      in 100% of cases, and this new information was mentioned in 50% of cases. A new
      informed consent was signed in 31% of cases and postoperative letter was written
      in 25% of cases. CONCLUSION: Information delivery traceability is mandatory. In
      case of complication leading to emergency reintervention, traceability should be
      done in the same way as prior to initial surgery.

PMID- 25863464
TI  - Lower extremity muscle activation and function in progressive task-oriented
      training on the supplementary tilt table during stepping-like movements in
      patients with acute stroke hemiparesis.
AB  - An effective and standardized method for applying a tilt table as a supplementary
      treatment in the early rehabilitation of stroke patients is still missing. The
      aim of this study was to determine the influence of progressive task-oriented
      training on the tilt table on the improvement in lower extremity (LE) muscle
      activation and clinical function in subjects with hemiplegia due to stroke.
      Thirty-nine subjects with acute stroke were randomly allocated to three groups;
      control group, tilt table group, and task-oriented training group on the tilt
      table, with 13 patients, respectively. All of the subjects received the routine
      therapy for half an hour, and subjects in the experimental groups additionally
      received training on two different tilt table applications for 20min a day, five
      times a week for three weeks. The effect of tilt table applications was assessed
      using the surface electromyography (EMG) analysis during stepping-like movements
      on the tilt table for LE muscle activation and clinical scores for function. Our
      results showed that there was a significantly greater increase in the EMG
      patterns of the extensors and flexors of the affected leg muscles during flexion
      and extension movements of both legs and clinical scores in patients undergoing
      the progressive task-oriented training on the tilt table compared to the other
      groups. These findings suggest that progressive task-oriented training on the
      tilt table can improve LE muscle activation and clinical scores of functional
      performance for early rehabilitation of subjects with acute stroke. 

PMID- 25863465
TI  - Repeated HIV Voluntary Counseling and Testing Increased Risk Behaviors Among Men
      Who Have Sex with Men in China: A Prospective Cohort Study.
AB  - High risk MSM are recommended to take up HIV voluntary counseling and testing
      (VCT) once every 6 months. 809 HIV-negative MSM in Beijing, China entered the 18
      month prospective cohort study; 228 joined an extended study at month 21. The
      majority (92.5 %) of the participants had taken up four rounds of VCT over the
      study period. HIV prevalence at months 0, 6, 12, 18 and 21 ranged from 2.5 to 6.3
      %; HIV incidences for the four intervals between the five visits ranged from 5.00
      to 14.28 per 100-person year. Despite experiencing repeated VCT, high levels of
      risk behaviors were reported at month 21. 18 % of the participants interviewed at
      month 21 self-reported increased in UAI and other risk behaviors, comparing
      recent and pre-baseline experiences. HIV transmission and risk behaviors had not
      been reduced by multiple rounds of VCT. Reasons behind apparent ineffectiveness
      and tailored repeated testing strategies need to be investigated. 

PMID- 25863466
TI  - Venues for Meeting Sex Partners and Partner HIV Risk Characteristics: HIV
      Prevention Trials Network (HPTN064) Women's HIV Seroincidence Study (ISIS).
AB  - Identifying venues where women meet sexual partners, particular partners who
      increase women's risk of acquiring HIV, could inform prevention efforts. We
      categorized venues where women enrolled in HPTN 064 reported meeting their last
      three sex partners as: (1) Formal, (2) Public, (3) Private, and (4) Virtual
      spaces. We used multinomial logistic regression to assess the association between
      these venues and women's individual characteristics and reports of their
      partners' HIV risk characteristics. The 2099 women reported meeting 3991
      partners, 51 % at Public, 30 % Private, 17 % Formal and 3 % at Virtual venues.
      Women meeting partners at Formal venues reported more education and condom use
      than women meeting partners at other venues. Fewer partners met through Formal
      venues had "high" risk characteristics for HIV than through other venues and
      hence may pose less risk of HIV transmission. HIV prevention interventions can
      help women choose partners with fewer risk characteristics across all venue
      types.

PMID- 25863468
TI  - Amnesia in an actor: Learning and re-learning of play passages despite severe
      autobiographical amnesia.
AB  - We describe the case of an accomplished actor, whom we term AB, who suffered
      severe amnesia following a cardiac arrest and hypoxic brain damage, affecting
      medial temporal and thalamic structures. His performance on standard episodic
      memory tests, and on measures of retrograde amnesia, including autobiographical
      memory, was severely impaired. When presented with passages from plays he had not
      appeared in, AB showed a severe impairment at the first learning trial, but
      thereafter showed a 'normal' learning curve for this semantically and
      syntactically complex material. On being presented with passages from plays he
      had performed in the past, AB did not show any recognition of them whatsoever, as
      one might expect from his severe episodic memory impairment. However, AB showed a
      striking benefit (savings score) in relearning passages he had previously
      performed, compared with new passages, despite not having any autobiographical
      recall of having performed the relearned passages before. Moreover, although his
      initial recall performance in learning these passages was impaired compared with
      healthy control actors of similar age and experience, AB demonstrated the same
      incremental learning rate on subsequent learning trials of the passages as did
      the controls. We conclude that, although severely impaired at the first learning
      trial (on both 'new' and 'old' passages), AB was able to employ his long
      established semantic and procedural skills to attempt the task, and that
      thereafter he showed a 'normal' rate of incremental learning from a lower
      baseline. 

PMID- 25863467
TI  - STI/HIV Sexual Risk Behavior and Prevalent STI Among Incarcerated African
      American Men in Committed Partnerships: The Significance of Poverty, Mood
      Disorders, and Substance Use.
AB  - African Americans face disproportionate sexually transmitted infection including
      HIV (STI/HIV), with those passing through a correctional facility at heightened
      risk. There is a need to identify modifiable STI/HIV risk factors among
      incarcerated African Americans. Project DISRUPT is a cohort study of incarcerated
      African American men recruited from September 2011 through January 2014 from
      prisons in North Carolina who were in committed partnerships with women at prison
      entry (N = 207). During the baseline (in-prison) study visit, participants
      responded to a risk behavior survey and provided a urine specimen, which was
      tested for STIs. Substantial proportions reported multiple partnerships (42 %),
      concurrent partnerships (33 %), and buying sex (11 %) in the 6 months before
      incarceration, and 9 % tested positive for an STI at baseline (chlamydia: 5.3 %,
      gonorrhea: 0.5 %, trichomoniasis: 4.9 %). Poverty and depression appeared to be
      strongly associated with sexual risk behaviors. Substance use was linked to
      prevalent STI, with binge drinking the strongest independent risk factor
      (adjusted odds ratio: 3.79, 95 % CI 1.19-12.04). There is a continued need for
      improved prison-based STI testing, treatment, and prevention education as well as
      mental health and substance use diagnosis. 

PMID- 25863469
TI  - Comparison of single-word and adjective-noun phrase production using event
      related brain potentials.
AB  - The present study builds upon findings from event-related potential (ERP) studies
      of single word production in order to shed light onto the mechanisms underlying
      the production of dual-word adjective-noun phrases (NPs). In a first experiment,
      we tested for potential differences elicited by visual stimuli varying in
      complexity -black and white line drawings, coloured line drawings, and arrays of
      drawings-in participants producing single nouns. Whilst naming latencies were
      similar for single noun production between visual stimuli conditions, ERPs
      differed between drawing arrays and single drawings in a time-window extending
      beyond early visual analysis. In a second experiment, different participants were
      asked to produce either single noun or adjective-noun dual-word phrases to black
      and-white and coloured line drawings, respectively. Adjective-noun phrase
      production (2W) resulted in naming latencies 53 msec longer than single noun (1W)
      production. Waveform amplitude and topographic analyses carried out on stimulus-
      and response-aligned ERPs indicated that the two conditions differed in a late
      time-window, with a topographic pattern for 2W lasting from 300 to 480 msec after
      picture presentation whereas the corresponding pattern for 1W production lasted
      from 300 to 450 msec. Since this time window has been previously associated with
      phonological encoding in single word production, this result suggests that the
      cost of planning the second word in dual-word production may be incurred during
      phonological encoding of the first word. The results are discussed in light of
      current models of single and multi-word production.

PMID- 25863470
TI  - Lateralization of gene expression in human language cortex.
AB  - Lateralization is an important aspect of the functional brain architecture for
      language and other cognitive faculties. The molecular genetic basis of human
      brain lateralization is unknown, and recent studies have suggested that gene
      expression in the cerebral cortex is bilaterally symmetrical. Here we have re
      analyzed two transcriptomic datasets derived from post mortem human cerebral
      cortex, with a specific focus on superior temporal and auditory language cortex
      in adults. We applied an empirical Bayes approach to model differential left
      right expression, together with gene ontology (GO) analysis and meta-analysis.
      There was robust and reproducible lateralization of individual genes and GO
      groups that are likely to fine-tune the electrophysiological and
      neurotransmission properties of cortical circuits, most notably synaptic
      transmission, nervous system development and glutamate receptor activity. Our
      findings anchor the cerebral biology of language to the molecular genetic level.
      Future research in model systems may determine how these molecular signatures of
      neurophysiological lateralization effect fine-tuning of cerebral cortical
      function, differently in the two hemispheres. 

PMID- 25863471
TI  - Association Between Sequence Variations in RCAN1 Promoter and the Risk of
      Sporadic Congenital Heart Disease in a Chinese Population.
AB  - The pathogenesis of congenital heart disease (CHD) is unclear. There is a high
      incidence of CHD in Down syndrome, in which RCAN1 (regulator of calcineurin 1)
      overexpression is observed. However, whether RCAN1 plays an important role in non
      syndromic CHD is unknown. This study investigates the relationship between
      sequence variations in the RCAN1 promoter and sporadic CHD. This was a case
      control study in which the RCAN1 promoter was cloned and sequenced in 128 CHD
      patients (median age 1.1 year) and 150 normal controls (median age 3.0 year). No
      mutation sites had been identified in this research. Three single-nucleotide (C
      to T) polymorphisms were detected: rs193289374, rs149048873 and rs143081213. The
      polymorphisms were not associated with CHD risk according to a logistic
      regression analysis. Functional assays in vitro showed that compared with the
      wild-type genotype, the rs149048873 polymorphism decreased, and the rs143081213
      increased, the RCAN1 promoter activity, though the rs193289374 polymorphism had
      no effect. In conclusion, the sequence variations in RCAN1 promoter are not major
      genetic factors involved in sporadic CHD, at least in the current research
      population.

PMID- 25863472
TI  - Hyperactivity in Attention-Deficit/Hyperactivity Disorder (ADHD): Impairing
      Deficit or Compensatory Behavior?
AB  - Excess gross motor activity (hyperactivity) is considered a core diagnostic
      feature of childhood ADHD that impedes learning. This view has been challenged,
      however, by recent models that conceptualize excess motor activity as a
      compensatory mechanism that facilitates neurocognitive functioning in children
      with ADHD. The current study investigated competing model predictions regarding
      activity level's relation with working memory (WM) performance and attention in
      boys aged 8-12 years (M = 9.64, SD = 1.26) with ADHD (n = 29) and typically
      developing children (TD; n = 23). Children's phonological WM and attentive
      behavior were objectively assessed during four counterbalanced WM tasks
      administered across four separate sessions. These data were then sequenced
      hierarchically based on behavioral observations of each child's gross motor
      activity during each task. Analysis of the relations among intra-individual
      changes in observed activity level, attention, and performance revealed that
      higher rates of activity level predicted significantly better, but not normalized
      WM performance for children with ADHD. Conversely, higher rates of activity level
      predicted somewhat lower WM performance for TD children. Variations in movement
      did not predict changes in attention for either group. At the individual level,
      children with ADHD and TD children were more likely to be classified as reliably
      Improved and Deteriorated, respectively, when comparing their WM performance at
      their highest versus lowest observed activity level. These findings appear most
      consistent with models ascribing a functional role to hyperactivity in ADHD, with
      implications for selecting behavioral treatment targets to avoid overcorrecting
      gross motor activity during academic tasks that rely on phonological WM. 

PMID- 25863474
TI  - Laparoscopic versus open appendectomy in children: the effect of surgical
      technique on healthcare costs.
AB  - BACKGROUND: Reducing healthcare costs while maintaining quality of care is one of
      the challenges of the current healthcare system. The purpose of this study was to
      compare the hospital charges accrued following laparoscopic (LA) and open (OA)
      appendectomies in the pediatric population. METHODS: We retrospectively reviewed
      all pediatric appendectomies (n = 264) performed from 2007 to 2013 at a single
      academic center. Subgroup analysis on charges and costs was performed on
      perforated and nonperforated LA and OA. RESULTS: A total of 195 (73.9%)
      appendectomies were performed laparoscopically. LA in both perforated and
      nonperforated groups was associated with higher surgical supply, operating room,
      and total hospital charges compared with OA. Surgical supply costs to the
      facility were higher by an average of $1,000 for both nonperforated and
      perforated appendicitis in the LA group. Length of stay and postoperative
      complications were comparable within all groups. CONCLUSIONS: In this study, LA
      is associated with significantly higher surgical costs and charges than OA
      without improvement in outcomes. Investigation into cost reduction strategies of
      laparoscopy should be a component of future clinical appendicitis research.

PMID- 25863473
TI  - Drug-induced renal damage in preterm neonates: state of the art and methods for
      early detection.
AB  - Only a small fraction of drugs widely used in neonatal intensive care units
      (NICU) are specifically authorized for this population. Even if unlicensed or off
      label use is necessary, it is associated with increased adverse drug reactions,
      which must be carefully weighed against expected benefits. In particular, renal
      damage is frequent among preterm babies, and is considered a predisposing factor
      for the development of chronic kidney disease in adulthood. Apart from specific
      conditions affecting premature neonates (e.g. respiratory distress syndrome,
      perinatal asphyxia), drugs play an important role in impairing renal function
      because of well-known nephrotoxicity and/or interaction with renal developmental
      factors. From a review of the available studies on drug use in NICU patients, we
      identified and described the most commonly administered drugs that are correlated
      to renal damage. Early detection of kidney injury is becoming an essential
      aspects for clinicians because of the limited number of biomarkers applicable in
      the neonatal population. Postnatal changes of biochemical processes that
      influence pharmacokinetic and pharmacodynamic aspects need to be further
      investigated in order to better understand the mechanisms of drug toxicity in
      this population. The most promising strategies for dose adjustment and
      therapeutic schemes are discussed. The purpose of this review was to describe
      current knowledge on drug use among premature babies and their implication in
      kidney injury development, as well as to highlight available strategies for early
      detection of renal damage. 

PMID- 25863475
TI  - Ki-67 expression in sclerosing adenosis and adjacent normal breast terminal
      ductal lobular units: a nested case-control study from the Mayo Benign Breast
      Disease Cohort.
AB  - Sclerosing adenosis (SA) increases risk for invasive breast cancer (BC) 2.1 times
      relative to that in the general population. Here, we sought to evaluate whether
      the proliferation marker Ki-67 stratifies risk among women with SA. A nested case
      control sample of patients with SA was obtained from the Mayo Clinic Benign
      Breast Disease Cohort. Ki-67 expression was evaluated in SA lesions and in the
      adjacent normal terminal duct lobular units (TDLU) in women who did (cases, n =
      133) or did not (controls, n = 239) develop BC. Ki-67 was scored by intensity and
      number of positively stained cells per one high-power field (magnification, *40)
      (40* HPF) for both SA and normal TDLU. Associations of Ki-67 expression with case
      control status were assessed using conditional logistic regression. Higher Ki-67
      expression was significantly associated with case-control status in both SA (P =
      0.03) and normal background TDLU (P = 0.006). For the SA lesion, >2 average
      positively stained cells/40* HPF showed an adjusted odds ratio (OR) of 1.9 (95 %
      CI, 1.1-3.4) compared to samples with an average of <=2 positively stained cells.
      For background TDLU, lobules with >2 but <=6 average positively stained cells
      showed an adjusted OR of 1.3-1.5, whereas those with an average of >6 positively
      stained cells had an OR of 2.4 (95 % CI, 1.1-5.3) compared to those with an
      average of <2 positively stained cells. Among women with SA, increased Ki-67
      expression in either the SA lesion or the normal background TDLU carried an
      approximately twofold increased odds of subsequent BC as compared to lower Ki-67
      expression. 

PMID- 25863476
TI  - The association between LEPR Q223R polymorphisms and breast cancer risk.
AB  - Recently, we have read with great interest the article entitled "The association
      between polymorphisms in the leptin receptor (LEPR) gene and risk of breast
      cancer: a systematic review and pooled analysis" published online by Wang et al.
      (Breast Cancer Res Treat 136:231-239, 2012). This article suggests that the A
      allele of LEPR gene rs1137101 variant was low-penetrant risk factor for
      developing breast cancer. The result is encouraging. Nevertheless, several key
      issues are worth noticing. 

PMID- 25863478
TI  - Bioaccumulation of heavy metals in oysters from the southern coast of Korea:
      assessment of potential risk to human health.
AB  - From 2009 to 2013, 80 oyster and 16 seawater samples were collected from the
      southern coast of Korea, including designated shellfish growing areas for export.
      The concentrations and bioaccumulation of heavy metals were determined, and a
      potential risk assessment was conducted to evaluate their hazards towards human
      consumption. The cadmium (Cd) concentration in oysters was the highest of three
      hazardous metals, including Cd, lead (Pb), and mercury (Hg), however, below the
      standards set by various countries. The metal bioaccumulation ratio in oysters
      was relatively high for zinc and Cd but low for Hg, Pb, arsenic, and chromium.
      The estimated dietary intakes of all heavy metals for oysters accounted for 0.02%
      17.75% of provisional tolerable daily intake. The hazard index for all samples
      was far <1.0, which indicates that the oysters do not pose an appreciable hazard
      to humans for the metal pollutants of study.

PMID- 25863477
TI  - The prevalence and spectrum of BRCA1 and BRCA2 mutations in Korean population:
      recent update of the Korean Hereditary Breast Cancer (KOHBRA) study.
AB  - The Korean Hereditary Breast Cancer (KOHBRA) study was established to evaluate
      the prevalence and spectrum of BRCA1/2 mutations in Korean breast cancer patients
      at risk for hereditary breast and ovarian cancer. A total of 2953 subjects (2403
      index patients and 550 family members of affected carriers) from 36 centers
      participated in this study between May 2007 and December 2013. All participants
      received genetic counseling and BRCA genetic testing. In total, 378 mutation
      carriers among 2403 index patients were identified. The prevalence of BRCA
      mutations in specific subgroups was as follows: 22.3 % (274/1228) for breast
      cancer patients with a family history of breast/ovarian cancers, 8.8 % (39/441)
      for patients with early-onset (<35 years) breast cancer without a family history,
      16.3 % (34/209) for patients with bilateral breast cancer, 4.8 % (1/21) for male
      patients with breast cancer, and 37.5 % (3/8) for patients with both breast and
      ovarian cancer. From an analysis of the mutation spectrum, 63 BRCA1 and 90 BRCA2
      different mutations, including 44 novel mutations, were identified. The c.7480
      (p.Arg2494Ter) mutation in BRCA2 (10.1 %) was the most commonly identified in
      this cohort. The KOHBRA study is the largest cohort to identify BRCA mutation
      carriers in Asia. The results suggest that the prevalence of BRCA mutations in
      familial breast cancer patients is similar to that among Western cohorts.
      However, some single risk factors without family histories (early-onset breast
      cancer, male breast cancer, or multiple organ cancers) may limit the utility of
      BRCA gene testing in the Korean population. 

PMID- 25863479
TI  - Trait canalization analysis of water quality, temperature, and developmental
      associations with early life stages of two fish species.
AB  - Evaluation of trait robustness based on environmental fluctuation in ontogenetic
      life stages are needed to evaluate stability and trait response during critical
      developmental events. Hardness, alkalinity, acidity, light intensity, and thermal
      differences were studied for trait canalization variation in morphometric,
      meristic, ontogenetic processes, and pigment characteristics. Trait canalization
      was observed with no statistical differences (p > 0.05) in mixed random two-way
      ANOVA comparisons between various block and treatment effects for hardness,
      alkalinity or acidity. Thermal block variation differences in six measures,
      including mandible length, yolk sac length, midpostanal depth, and head width,
      incubation, and hatching length, varied significantly (p <= 0.05) with declining
      temperatures. Water quality and thermal attributes exhibited trait canalization
      and did not increase character state variation in the early life stage
      morphological expression, which result in stable phenotypic inheritance rather
      than variable environmental conditions during embryonic and larval development. 

PMID- 25863481
TI  - Second-order nonlinear optical properties of dithienophenazine and TTF
      derivatives: A butterfly effect of dimalononitrile substitutions.
AB  - Using density functional theory (DFT) methods, the nonlinear optical (NLO)
      properties have been calculated with strong donor-pi-conjugation-acceptor
      configurations. The static first hyperpolarizability (beta0) and dynamic
      (frequency dependent) electric field induced second harmonic generation (EFISHG)
      first hyperpolarizability (MUbeta) are calculated for all designed systems. Our
      DFT calculations show dithienophenazine merged TTF (2) holds larger beta0
      amplitudes (beta0=21.04*10(3)a.u.) as compared to its corresponding compounds of
      TTF merged-difurophenazine (1), dicyclopentaphenazine (3) and dipyrrolophenazine
      (4) derivatives having beta0 amplitudes of 16.25*10(3), 12.69*10(3), and
      18.38*10(3)a.u., respectively. Furthermore, substitution of dimalononitrile
      [C(CN)2]2 groups at acceptor end of these compounds results in new derivatives 1a
      4a, respectively. Interestingly, a butterfly effect on first hyperpolarizability
      of all systems 1a-4a has been spotted, which not only results in their robustly
      larger beta0 amplitudes but also changes the increasing order of beta0 amplitudes
      from systems 3<1<4<2 to 1a<2a<3a<4a at both PBE0/6-31G* and CAM-B3LYP/6-31+G*
      levels of theory. For example, the increase in beta0 amplitudes of systems 1a,
      2a, 3a and 4a are 3, 3, 5, and 19 times as compared with their corresponding non
      dimalononitrile derivatives at PBE0/6-31G* level of theory, respectively.
      Remarkably, unlike the static first hyperpolarizability, the dynamic EFISHG
      hyperpolarizability (MUbetaomega) has the largest value for system 4a with its
      amplitudes of 1378.59*10(-46) and 1349.40*10(-46)esu, at PBE0/6-31G* and CAM
      B3LYP/6-31+G* levels of theory, respectively. TD-DFT calculations have been
      performed to trace the origin of first hyperpolarizability. It has been found
      that the lower transition energy and higher oscillator strengths cause robustly
      large amplitudes especially in systems 3a and 4a, which consequently stems in
      strong donor-pi-conjugation-acceptor configuration of these systems. Thus the
      present results intrigue the butterfly effect of a two-step substitution on NLO
      properties of TTF merged dithienophenazine compounds that can be used as an
      efficient NLO material. 

PMID- 25863480
TI  - Pea lectin receptor-like kinase functions in salinity adaptation without yield
      penalty, by alleviating osmotic and ionic stresses and upregulating stress
      responsive genes.
AB  - Lectin receptor-like kinases (LecRLKs) are members of RLK family composed of
      lectin-like extracellular recognition domain, transmembrane domain and
      cytoplasmic kinase domain. LecRLKs are plasma membrane proteins believed to be
      involved in signal transduction. However, most of the members of the protein
      family even in plants have not been functionally well characterized. Herein, we
      show that Pisum sativum LecRLK (PsLecRLK) localized in plasma membrane systems
      and/or other regions of the cell and its transcript upregulated under salinity
      stress. Overexpression of PsLecRLK in transgenic tobacco plants confers salinity
      stress tolerance by alleviating both the ionic as well the osmotic component of
      salinity stress. The transgenic plants show better tissue compartmentalization of
      Na(+) and higher ROS scavenging activity which probably results in lower membrane
      damage, improved growth and yield maintenance even under salinity stress. Also,
      expression of several genes involved in cellular homeostasis is perturbed by
      PsLecRLK overexpression. Alleviation of osmotic and ionic components of salinity
      stress along with reduced oxidative damage and upregulation of stress-responsive
      genes in transgenic plants under salinity stress conditions could be possible
      mechanism facilitating enhanced stress tolerance. This study presents PsLecRLK as
      a promising candidate for crop improvement and also opens up new avenue to
      investigate its signalling pathway. 

PMID- 25863482
TI  - Development of a SYBR-based real-time PCR to detect rabbit hemorrhagic disease
      virus (RHDV) and analyze its tissue distribution in experimentally infected
      rabbits.

PMID- 25863483
TI  - Is trait resilience characterized by specific patterns of attentional bias to
      emotional stimuli and attentional control?
AB  - BACKGROUND AND OBJECTIVES: Attentional processes have been suggested to play a
      crucial role in resilience defined as positive adaptation facing adversity.
      However, research is lacking on associations between attentional biases to
      positive and threat-related stimuli, attentional control and trait resilience.
      METHODS: Data stem from the follow-up assessment of a longitudinal study
      investigating mental health and related factors among German soldiers. Trait
      resilience was assessed with the Connor-Davidson Resilience Scale and attentional
      control with the Attentional Control Scale. A subset of n = 198 soldiers also
      completed a dot probe task with happy, neutral and threatening faces. RESULTS:
      Attentional control was positively related to trait resilience. Results revealed
      no associations between both attentional biases and trait resilience. However,
      there was a negative association between attentional bias to threat and trait
      resilience when attentional control was low and a positive association between
      attentional bias to threat and trait resilience when attentional control was
      high. No such associations were found for attentional bias to positive stimuli.
      LIMITATIONS: Generalizability to other populations may be limited since we
      exclusively focused on male soldiers. Also, the cross-sectional design does not
      allow for causal conclusions. CONCLUSIONS: Findings suggest that attentional
      processing may promote trait resilience. Future research on preventive
      interventions should consider these findings.

PMID- 25863484
TI  - The efficacy of acupoint stimulation in the treatment of psychological distress:
      A meta-analysis.
AB  - BACKGROUND AND OBJECTIVES: Emotional Freedom Techniques (EFT) is a type of
      therapy involving the stimulation of acupuncture points while using a spoken
      affirmation to target a psychological issue. While some studies cite data
      indicating EFT is highly efficacious, findings in other studies are unconvincing.
      The aim of this meta-analysis was to examine the effect of EFT, particular
      acupoint stimulation, in the treatment of psychological distress. METHOD: A
      systematic review of the literature identified 18 randomised control trials
      published in peer reviewed journals involving a total of 921 participants.
      RESULTS: A moderate effect size (Hedge's g = -0.66: 95% CI: -0.99 to -0.33) and
      significantly high heterogeneity (I(2) = 80.78) across studies was found using a
      random effects model indicating that EFT, even after removing outliers (decreases
      in I(2) = 72.32 and Hedge's g = -0.51:95% CI:-0.78 to -0.23), appears to produce
      an effect. The analysis involved 12 studies comparing EFT with waitlist controls,
      5 with adjuncts and only 1 comparison with an alternate treatment. Meta
      regression and subgroup analyses were conducted to examine the effect of
      moderators on effect size of symptom change following EFT. CONCLUSIONS: Due to
      methodological shortcomings, it was not possible to determine if the effect is
      due to acupoint stimulation or simply due to treatment elements common with other
      therapies.

PMID- 25863485
TI  - Perceptual and conceptual similarities facilitate the generalization of
      instructed fear.
AB  - BACKGROUND AND OBJECTIVES: Learned fear can generalize to neutral events due
      their perceptual and conceptual similarity with threat relevant stimuli. This
      study simultaneously examined these forms of generalization to model the
      expansion of fear in anxiety disorders. METHODS: First, artificial categories
      involving sounds, nonsense words and animal-like objects were established. Next,
      the words from one category were paired with threatening information while the
      words from the other category were paired with safety information. Lastly, we
      examined if fear generalized to (i) the conceptually related animal-like objects
      and (ii) other animal like-objects that were perceptually similar. This was
      measured using behavioral avoidance, US expectancy ratings and self-reported
      stimulus valence. RESULTS: Animal-like objects conceptually connected to the
      aversive words evoked heightened fear. Perceptual variants of these animal-like
      objects also elicit fear. LIMITATIONS: Future research would benefit from the use
      of online-US expectancy ratings and physiological measures of fear. CONCLUSIONS:
      Investigating the role of both perceptual and conceptual fear generalization is
      important to better understand the etiology of anxiety disorders symptoms.

PMID- 25863486
TI  - Hemoglobin concentration and incident metabolic syndrome: a population-based
      large-scale cohort study.
AB  - Previous cross-sectional studies revealed an association between hemoglobin
      concentration and a prevalence of metabolic syndrome (MetS). However, the
      association between hemoglobin concentration and incident MetS remains to be
      elucidated. Thus, the aim of this study was to investigate the association
      between hemoglobin concentration and incident MetS. We enrolled 2695 subjects
      (1454 men and 1241 women) and performed 8-year follow-up cohort study. MetS was
      diagnosed, according to the joint interim statement, when a subject had three or
      more of the following components: hypertension; hyperglycemia;
      hypertriglyceridemia; low high-density lipoprotein cholesterol; and abdominal
      obesity. Logistic regression analyses were performed to assess the impact of
      hemoglobin concentration on incident MetS by adjusting for age, body mass index,
      lifestyle factors, including smoking status, habit of alcohol and habit of
      exercise, systolic blood pressure, fasting plasma glucose, triglycerides, high
      density lipoprotein cholesterol, creatinine, and uric acid. The highest (>=157
      g/L) and third (151-156 g/L) hemoglobin concentration quartiles were associated
      with the increased risk of incident MetS compared to the lowest (<145 g/L)
      hemoglobin concentration quartile after adjusting for covariates in men
      (multivariate odds ratio (OR) 2.24, 95% CI 1.34-3.85, P = 0.0021 and multivariate
      OR 2.03, 95% CI 1.21-3.45, P = 0.0070). On the other hand, there was no
      association between hemoglobin concentration and incident MetS in women.
      Hemoglobin concentration was a novel risk marker for incident MetS in men.

PMID- 25863488
TI  - Serum aminotransferase levels and angiographic coronary artery disease in
      octogenarians.

PMID- 25863487
TI  - Somatic amplifications and deletions in genome of papillary thyroid carcinomas.
AB  - Somatic gene copy number variation contributes to tumor progression. Using
      comparative genomic hybridization (CGH) array, the presence of genomic imbalances
      was evaluated in a series of 27 papillary thyroid carcinomas (PTCs). To detect
      only somatic imbalances, for each sample, the reference DNA was from normal
      thyroid tissue of the same patient. The presence of the BRAF V600E mutation was
      also evaluated. Both amplifications and deletions showed an uneven distribution
      along the entire PTC cohort; amplifications were more frequent than deletions
      (mean values of 17.5 and 7.2, respectively). Number of aberration events was not
      even among samples, the majority of them occurring only in a small fraction of
      PTCs. Most frequent amplifications were detected at regions 2q35, 4q26, and
      4q34.1, containing FN1, PDE5A, and GALNTL6 genes, respectively. Most frequent
      deletions occurred at regions 6q25.2, containing OPMR1 and IPCEF1 genes and
      7q14.2, containing AOAH and ELMO1 genes. Amplification of FN1 and PDE5A genomic
      regions was confirmed by quantitative PCR. Frequency of amplifications and
      deletions was in relationship with clinical features and BRAF mutation status of
      tumor. In fact, according to the American Joint Committee on Cancer stage and
      American Thyroid Association (ATA) risk classification, amplifications are more
      frequent in higher risk samples, while deletions tend to prevail in the lower
      risk tumors. Analysis of single aberrations according to the ATA risk grouping
      shows that amplifications containing PDE5A, GALNTL6, DHRS3, and DOCK9 genes are
      significantly more frequent in the intermediate/high risk group than in the low
      risk group. Thus, our data would indicate that analysis of somatic genome
      aberrations by CGH array can be useful to identify additional prognostic
      variables. 

PMID- 25863489
TI  - Adrenalectomy for metastasis: long-term results and predictors of survival.
AB  - The purpose of this study was to analyze our experience with surgically treated
      isolated adrenal metastases in order to find those factors which can
      significantly affect survival. This method includes a retrospective single-center
      chart review. We evaluated how overall survival and disease-free survival (DFS)
      were influenced by demographic, tumor, and procedure-related variables. Thirty
      seven adrenalectomies were performed in 34 patients. Procedures included 25
      laparoscopic and 12 open adrenalectomies. Median follow-up was 49 months. Median
      overall survival was 63 months. Patients submitted to laparoscopic approach had a
      median survival of 57 months while it was 65 months for those who underwent open
      procedure (p = 0.67). DFS was 30 months, and these were 35 and 25 months after
      laparoscopic approach and open approach, respectively (p = 0.59). The concurrent
      resection of the adrenal metastasis with the primary tumor was the only factor
      influencing DFS (HR 6.8 95 % CI 1.2-37.3, p = 0.02). Patients with non-small cell
      lung cancer (n = 15) had a median survival of 63 months and DFS of 35 months. Our
      experience confirms that adrenalectomy, regardless of the surgical approach, can
      offer durable disease-free and overall survival outcomes for surgical candidates
      with isolated adrenal metastases.

PMID- 25863491
TI  - Free and bound plasma leptin in anorexia nervosa patients during a refeeding
      program.

PMID- 25863490
TI  - The cAMP analogs have potent anti-proliferative effects on medullary thyroid
      cancer cell lines.
AB  - The oncogenic activation of the rearranged during transfection (RET) proto
      oncogene has a main role in the pathogenesis of medullary thyroid cancer (MTC).
      Several lines of evidence suggest that RET function could be influenced by cyclic
      AMP (cAMP)-dependent protein kinase A (PKA) activity. We evaluated the in vitro
      anti-tumor activity of 8-chloroadenosine-3',5'-cyclic monophosphate (8-Cl-cAMP)
      and PKA type I-selective cAMP analogs [equimolar combination of the 8
      piperidinoadenosine-3',5'-cyclic monophosphate (8-PIP-cAMP) and 8
      hexylaminoadenosine-3',5'-cyclic monophosphate (8-HA-cAMP) in MTC cell lines (TT
      and MZ-CRC-1)]. 8-Cl-cAMP and the PKA I-selective cAMP analogs showed a potent
      anti-proliferative effect in both cell lines. In detail, 8-Cl-cAMP blocked
      significantly the transition of TT cell population from G2/M to G0/G1 phase and
      from G0/G1 to S phase and of MZ-CRC-1 cells from G0/G1 to S phase. Moreover, 8-Cl
      cAMP induced apoptosis in both cell lines, as demonstrated by FACS analysis for
      annexin V-FITC/propidium iodide, the activation of caspase-3 and PARP cleavage.
      On the other hand, the only effect induced by PKA I-selective cAMP analogs was a
      delay in G0/G1-S and S-G2/M progression in TT and MZ-CRC-1 cells, respectively.
      In conclusion, these data demonstrate that cAMP analogs, particularly 8-Cl-cAMP,
      significantly suppress in vitro MTC proliferation and provide rationale for a
      potential clinical use of cAMP analogs in the treatment of advanced MTC. 

PMID- 25863492
TI  - N-Acylsulfonamides strongly inhibit human carbonic anhydrase isoenzymes I and II.
AB  - Sulfonamides represent a significant class of biologically active compounds that
      inhibit carbonic anhydrase (CA, EC.: 4.2.1.1) isoenzymes involved in different
      pathological and physiological events. Sulfonamide CA inhibitors are used
      therapeutically as diuretic, antiglaucoma, antiobesity and anticancer agents. A
      series of new sulfonamides were synthesized using imides and tosyl chloride as
      starting materials. These N-acylsulfonamides efficiently inhibited the cytosolic
      human carbonic anhydrase isoenzymes I, and II (hCA I, and II), with nanomolar
      range inhibition constants ranging between 36.4 +/- 6.0-254.6 +/- 18.0 and 58.3
      +/- 0.6-273.3 +/- 2.5 nM, respectively.

PMID- 25863493
TI  - Synthesis, antinociceptive and anti-inflammatory effects of porphyrins.
AB  - Porphyrins are natural compounds with several biological activities. We report
      the synthesis and the evaluation of the anti-inflammatory and antinociceptive
      effects of 4 porphyrins: 5,10,15,20-tetraphenylporphyrin (TPP), 5,10,15,20
      tetra(4'-fluorophenyl)porphyrin (TpFPP), 5,10,15,20-tetra(4'
      chlorophenyl)porphyrin (TpClPP), and 5,10,15,20-tetra(4'-bromophenyl)porphyrin
      (TpBrPP). The in vitro anti-inflammatory effects were evaluated on heat-induced
      hemolysis. The antinociceptive effects were evaluated using the hot plate and
      formalin tests. The in vivo anti-inflammatory assays were tested on the acute and
      chronic TPA (12-O-tetradecanoylphorbol 13-acetate) method to induce ear edema.
      The anti-arthritic effects were evaluated using carrageenan kaolin induced
      arthritis (CKIA). All porphyrins inhibited hemolysis with similar potency than
      naproxen (NPX). In the antinociceptive tests, all porphyrins tested at 200mg/kg
      showed similar effects compared to 100mg/kg NPX. In the in vivo anti-inflammatory
      acute assay, only three porphyrins (TPP, TpFPP and TpBrPP) decreased inflammation
      with similar activity than 2mg/ear indomethacin (IND). Further anti-inflammatory
      experiments were carried out with TPP, TpFPP and TpBrPP. In the in vivo anti
      inflammatory chronic assay, porphyrins decreased inflammation with similar
      activity than 8mg/kg IND. Porphyrins tested at 200mg/kg showed anti-arthritic
      effects. The antinociceptive, anti-inflammatory and arthritic activities of
      porphyrins suggest that these compounds might be a good alternative for the
      treatment of inflammatory diseases. 

PMID- 25863495
TI  - How do students' perceptions of research and approaches to learning change in
      undergraduate research?
AB  - OBJECTIVE: This study aimed to examine how students' perceptions of research and
      learning change through participation in undergraduate research and to identify
      the factors that affect the process of their engagement in research projects.
      METHODS: This qualitative study has drawn on phenomenography as research
      methodology to explore third-year medical students' experiences of undergraduate
      research from participants' perspectives (n=14). Data included semi-structured
      individual interviews conducted as pre and post reflections. Thematic analysis of
      pre-course interviews combined with researcher-participant observations informed
      design of end-of-course interview questions. RESULTS: Phenomenographic data
      analysis demonstrated qualitative changes in students' perceptions of research.
      At the beginning of the course, the majority of students ex-pressed a relatively
      narrow definition of research, focusing on the content and outcomes of scientific
      research. End-of-course reflections indicated increased attention to research
      processes including researcher autonomy, collaboration and knowledge construction
      processes. Furthermore, acknowledgement of the linkage between research and
      learning processes indicated an epistemological change leading them to take a
      deep approach to learning in undergraduate research. Themes included: an
      inquiring mind, synthesis of knowledge, active participation, collaborative and
      reflective learning. However, they also encountered some difficulties in
      undertaking group research projects. These were attributed to their prior
      learning experiences, differences in valuing towards interpersonal communication,
      understanding of the research process, and social relationships with others.
      CONCLUSIONS: This study provided insights into the potential for undergraduate
      research in medical education. Medical students' awareness of the linkage between
      research and learning may be one of the most important outcomes in the
      undergraduate research process.

PMID- 25863494
TI  - Hyperglycemia down-regulates cGMP-dependent protein kinase I expression in first
      trimester cytotrophoblast cells.
AB  - Diabetes in pregnancy is associated with microvascular complications and a higher
      incidence of preeclampsia. The regulatory signaling pathways involving nitric
      oxide, cGMP, and cGMP-dependent protein kinase (PKG) have been shown to be down
      regulated under diabetic conditions and contribute to the pathogenesis of
      vascular complications in diabetes. The present study was undertaken to
      investigate how high glucose concentrations regulate PKG expression in
      cytotrophoblast cells (CTBs). Human CTBs (Sw. 71) were treated with 45, 135, 225,
      495, or 945 mg/dL glucose for 48 h. Some cells were pretreated with a p38
      inhibitor (10 MUM SB203580) or 10 MUM rosiglitazone. After treatment, the cell
      lysates were subjected to measure the expression of protein kinase G1alpha
      (PKG1alpha), protein kinase G1beta (PKG1beta), soluble guanylate cyclase 1alpha
      (sGC1alpha), and soluble guanylate cyclase 1 beta (sGC1beta) by Western blot.
      Statistical comparisons were performed using analysis of variance with Duncan's
      post hoc test. The expressions of PKG1alpha, PKG1beta, sGC1alpha, and sGC1beta
      were significantly down-regulated (p < 0.05) in CTBs treated with >135 mg/dL
      glucose compared to basal (45 mg/dL). The hyperglycemia-induced down-regulation
      of cGMP and cGMP-dependent PKG were attenuated by the SB203580 or rosiglitazone
      pretreatment. Exposure of CTBs to excess glucose down-regulates cGMP and cGMP
      dependent PKG, contributing to the development of vascular complications in
      diabetic mothers during pregnancy. The attenuation of hyperglycemia-induced down
      regulation of PKG proteins by SB203580 or rosiglitazone pretreatment further
      suggests the involvement of stress signaling mechanisms in this process.

PMID- 25863497
TI  - Spatial heterogeneity and host repression in fig-fig wasp mutualism.
AB  - It is generally believed that physical heterogeneity in common resource or
      evolutionary restraint can sufficiently prevent direct conflict between host and
      symbionts in mutualism systems. Our data on fig/fig wasp reciprocal mutualism
      (Ficus racemosa), however, show that structural barriers of female flowers or
      genetic constraints of pollinators previously hypothesized exist, but cannot
      sufficiently maintain the mutualism stability. The results show that a positive
      relationship between seed and wasp production could be maintained in warm season,
      which might be because of density dependence restraint among foundresses and
      their low oviposition and pollination efficiency, keeping common resource (female
      flowers) utilization unsaturated. Whilst, a negative correlation between wasp
      offspring and viable seed production was also observed in cold season, which
      might be that the increased oviposition and pollination efficiency maximized the
      common resource utilization. The fitness trade-off between fig and pollinator
      wasps is greatly affected by environmental or ecological variations. The local
      stability might result from temporal low exploitation efficiency of pollinators
      together with interference competition among pollinators. We suggest that host
      repression through the active regulation of bract closure, which can create
      interference competition among the foundresses and prevent extra more foundresses
      sequential entry in fruit cavities, would help the figs avoiding the cost of over
      exploitation. This essentially takes the same role as sanctioning of cheating or
      competitive behaviors. 

PMID- 25863496
TI  - Developing injectable nanomaterials to repair the heart.
AB  - Injectable nanomaterials have been designed for the treatment of myocardial
      infarction, particularly during the acute stages of inflammation and injury.
      Among these strategies, injectable nanofibrous hydrogel networks or nanoparticle
      complexes may be delivered alone or with a therapeutic to improve heart function.
      Intramyocardial delivery of these materials localizes treatments to the site of
      injury. As an alternative, nanoparticles may be delivered intravenously, which
      provides the ultimate minimally invasive approach. These systems take advantage
      of the leaky vasculature after myocardial infarction, and may be designed to
      specifically target the injured region. The translational applicability of both
      intramyocardial and intravenous applications may provide safe and effective
      solutions upon optimizing the timing of the treatments and biodistribution. 

PMID- 25863498
TI  - WRKY transcription factors: links between phytohormones and plant processes.

PMID- 25863499
TI  - Diabetes increases renovascular impedance in patients with liver cirrhosis.
AB  - Renal failure is a common complication of cirrhosis and is associated with poor
      prognosis. Several reports have demonstrated the clinical utility of renal
      resistive indices in the assessment of renal function in cirrhosis patients. It
      is unknown whether the occurrence of diabetes affects renal haemodynamic indices
      in patients with cirrhosis. Therefore, the aim of our study was to compare renal
      Doppler indices in cirrhotic patients with and without type 2 diabetes mellitus
      (T2DM) and in diabetics without cirrhosis, and to relate the Doppler parameters
      to albuminuria. We evaluated 89 consecutive patients with normal renal
      functioning, including 37 with cirrhosis and T2DM (CD-Group), 41 with cirrhosis
      without diabetes (C-Group) and 11 with diabetes without cirrhosis (D-Group). The
      kidney pulsatility index (PI) and resistance index (RI) were measured by Doppler
      ultrasound. Renal function was expressed as the estimated glomerular filtration
      rate (eGFR) using the modification of diet in renal disease (MDRD) formula.
      Microalbuminuria (uAlb) was also evaluated. No significant differences were
      observed with respect to age, the Child-Pugh class or the serum creatinine level.
      The eGFR was mildly reduced in the CD-Group compared with the C-Group and D
      Group, and uAlb was present in 24.4 % of the patients in the CD-Group and in 9 %
      of those in the D-Group. The PI and RI were significantly increased in the CD
      Group and D-Group compared with the C-Group. Both the PI and RI were
      significantly associated with uAlb independent of age and Child-Pugh class. The
      novel finding of this study was that T2DM potentially impairs renal haemodynamics
      in patients with cirrhosis.

PMID- 25863500
TI  - Assessment of public health risk associated with viral contamination in harvested
      urban stormwater for domestic applications.
AB  - Capturing stormwater is becoming a new standard for sustainable urban stormwater
      management, which can be used to supplement water supply portfolios in water
      stressed cities. The key advantage of harvesting stormwater is to use low impact
      development (LID) systems for treatment to meet water quality requirement for non
      potable uses. However, the lack of scientific studies to validate the safety of
      such practice has limited its adoption. Microbial hazards in stormwater,
      especially human viruses, represent the primary public health threat. Using
      adenovirus and norovirus as target pathogens, we investigated the viral health
      risk associated with a generic scenario of urban stormwater harvesting practice
      and its application for three non-potable uses: 1) toilet flushing, 2) showering,
      and 3) food-crop irrigation. The Quantitative Microbial Risk Assessment (QMRA)
      results showed that food-crop irrigation has the highest annual viral infection
      risk (median range: 6.8*10(-4)-9.7*10(-1) per-person-per-year or pppy), followed
      by showering (3.6*10(-7)-4.3*10(-2)pppy), and toilet flushing (1.1*10(-7)-1.3*10(
      4)pppy). Disease burden of each stormwater use was ranked in the same order as
      its viral infection risk: food-crop irrigation>showering>toilet flushing. The
      median and 95th percentile risk values of toilet-flushing using treated
      stormwater are below U.S. EPA annual risk benchmark of <=10(-4)pppy, whereas the
      disease burdens of both toilet-flushing and showering are within the WHO
      recommended disease burdens of <=10(-6)DALYspppy. However, the acceptability of
      showering risk interpreted based on the U.S. EPA and WHO benchmarks is in
      disagreement. These results confirm the safety of stormwater application in
      toilet flushing, but call for further research to fill the data gaps in risk
      modeling as well as risk benchmarks. 

PMID- 25863501
TI  - Geophysical and hydrogeological characterisation of the impacts of on-site
      wastewater treatment discharge to groundwater in a poorly productive bedrock
      aquifer.
AB  - Contaminants discharging from on-site wastewater treatment systems (OSWTSs) can
      impact groundwater quality, threatening human health and surface water
      ecosystems. Risk of negative impacts becomes elevated in areas of extreme
      vulnerability with high water tables, where thin unsaturated intervals limit
      vadose zone attenuation. A combined geophysical/hydrogeological investigation
      into the effects of an OSWTS, located over a poorly productive aquifer (PPA) with
      thin subsoil cover, aimed to characterise effluent impacts on groundwater.
      Groundwater, sampled from piezometers down-gradient of the OSWTS percolation area
      displayed spatially erratic, yet temporally consistent, contaminant
      distributions. Electrical resistivity tomography identified an area of gross
      groundwater contamination close to the percolation area and, when combined with
      seismic refraction and water quality data, indicated that infiltrating effluent
      reaching the water table discharged to a deeper more permeable zone of weathered
      shale resting on more competent bedrock. Subsurface structure, defined by
      geophysics, indicated that elevated chemical and microbiological contaminant
      levels encountered in groundwater samples collected from piezometers, down
      gradient of sampling points with lower contaminant levels, corresponded to those
      locations where piezometers were screened close to the weathered shale/competent
      rock interface; those immediately up-gradient were too shallow to intercept this
      interval, and thus the more impacted zone of the contaminant plume. Intermittent
      occurrence of faecal indicator bacteria more than 100m down gradient of the
      percolation area suggested relatively short travel times. Study findings
      highlight the utility of geophysics as part of multidisciplinary investigations
      for OSWTS contaminant plume characterisation, while also demonstrating the
      capacity of effluent discharging to PPAs to impact groundwater quality at
      distance. Comparable geophysical responses observed in similar settings across
      Ireland suggest the phenomena observed in this study are more widespread than
      previously suspected. 

PMID- 25863502
TI  - Ragweed (Ambrosia) pollen source inventory for Austria.
AB  - This study improves the spatial coverage of top-down Ambrosia pollen source
      inventories for Europe by expanding the methodology to Austria, a country that is
      challenging in terms of topography and the distribution of ragweed plants. The
      inventory combines annual ragweed pollen counts from 19 pollen-monitoring
      stations in Austria (2004-2013), 657 geographical observations of Ambrosia
      plants, a Digital Elevation Model (DEM), local knowledge of ragweed ecology and
      CORINE land cover information from the source area. The highest mean annual
      ragweed pollen concentrations were generally recorded in the East of Austria
      where the highest densities of possible growth habitats for Ambrosia were
      situated. Approximately 99% of all observations of Ambrosia populations were
      below 745m. The European infection level varies from 0.1% at Freistadt in
      Northern Austria to 12.8% at Rosalia in Eastern Austria. More top-down Ambrosia
      pollen source inventories are required for other parts of Europe. CAPSULE
      ABSTRACT: A method for constructing top-down pollen source inventories for
      invasive ragweed plants in Austria, a country that is challenging in terms of
      topography and ragweed distribution.

PMID- 25863503
TI  - Occurrence and risk assessment of phthalate esters (PAEs) in vegetables and soils
      of suburban plastic film greenhouses.
AB  - Phthalate esters (PAEs) are suspected of having adverse effects on human health
      and have been frequently detected in soils and vegetables. The present study
      investigated their occurrence and composition in plastic film greenhouse soil
      vegetable systems and assessed their potential health risks to farmers exposed to
      these widespread pollutants. Six priority control phthalates, namely dimethyl
      phthalate (DMP), diethyl phthalate (DEP), di-n-butyl phthalate (DnBP), butyl
      benzyl phthalate (BBP), di-(2-ethylhexyl) phthalate (DEHP) and di-n-octyl
      phthalate (DnOP), were determined in 44 plastic film greenhouse vegetables and
      corresponding soils. Total PAEs ranged from 0.51 to 7.16mgkg(-1) in vegetables
      and 0.40 to 6.20mgkg(-1) in soils with average concentrations of 2.56 and
      2.23mgkg(-1), respectively. DnBP, DEHP and DnOP contributed more than 90% of the
      total PAEs in both vegetables and soils but the proportions of DnBP and DnOP in
      vegetables were significantly (p<0.05) higher than in soils. The average
      concentrations of PAEs in pot herb mustard, celery and lettuce were >3.00mgkg(-1)
      but were <2.50mgkg(-1) in the corresponding soils. Stem and leaf vegetables
      accumulated more PAEs. There were no clear relationships between vegetable and
      soil PAEs. Risk assessment indicates that DnBP, DEHP and DnOP exhibited elevated
      non-cancer risk with values of 0.039, 0.338 and 0.038, respectively. The
      carcinogenic risk of DEHP was about 3.94*10(-5) to farmers working in plastic
      film greenhouses. Health risks were mainly by exposure through vegetable
      consumption and soil ingestion. 

PMID- 25863504
TI  - Arsenic extraction and speciation in plants: Method comparison and development.
AB  - We compared four methods to extract arsenic (As) from three different plants
      containing different As levels for As speciation with the goal of developing a
      more efficient method, i.e., As-hyperaccumulator Pteris vittata at 459-7714mgkg(
      1), rice seedling at 53.4-574mgkg(-1), and tobacco leaf at 0.32-0.35mgkg(-1). The
      four methods included heating with dilute HNO3, and sonication with phosphate
      buffered solution, methanol/water, and ethanol/water, with As being analyzed
      using high-performance liquid chromatography coupled with inductively-coupled
      plasma mass spectrometry (HPLC-ICP-MS). Among the four methods, the ethanol/water
      method produced the most satisfactory extraction efficiency (~80% for the roots
      and >85% for the fronds) without changing As species based on P. vittata. The
      lower extraction efficiency from P. vittata roots was attributed to its dominance
      by arsenate (82%) while arsenite dominated in the fronds (89%). The ethanol/water
      method used sample:solution ratio of 1:200 (0.05g:10mL) with 50% ethanol and 2h
      sonication. Based on different extraction times (0.5-2h), ethanol concentrations
      (25-100%) and sample:solution ratios (1:50-1:300), the optimized ethanol/water
      method used less ethanol (25%) and time (0.5h for the fronds and 2h for the
      roots). Satisfactory extraction was also obtained for tobacco leaf (78-92%) and
      rice seedlings (~70%) using the optimized method, which was better than the other
      three methods. Based on satisfactory extraction efficiency with little change in
      As species during extraction from three plants containing different As levels,
      the optimized method has the potential to be used for As speciation in other
      plants. 

PMID- 25863505
TI  - Framingham risk score modifies the effect of PM10 on heart rate variability.
AB  - Health conditions may greatly modify the association between particulate matter
      (PM) and heart rate variability (HRV), but whether the modification of PM effect
      by coronary artery disease (CAD) risk status depends on the PM levels remains
      unknown. We investigated the associations between personal exposures to PM with
      aerodynamic diameter of <=10MUm (PM10) and <=2.5MUm (PM2.5) and concurrent HRV,
      and whether the effect of PM on HRV was modified by Framingham risk score (FRS)
      in healthy subjects with different PM exposure levels. Personal exposures to PM10
      and PM2.5 were measured for 24h in 152 volunteers of community residents who were
      free of cardiovascular disease in two cities (Zhuhai and Wuhan) that differ in
      air quality. Simultaneously, 24h HRV indices were obtained from 3-channel Holter
      monitor. FRS was calculated based on age, sex, lipid profiles, blood pressure,
      diabetes, and smoking status. Linear regression models were constructed after
      adjusting for potential confounders. We found significant decrease in total power
      (TP) and low power (LF) with increased PM10 concentrations (P for trend<0.05) in
      the high PM levels city (Wuhan) and total population, but not in the low PM
      levels city (Zhuhai). We also observed significant modification of FRS on PM10
      effect in Wuhan. Interestingly, elevated PM10 was associated in a greater
      decreased HRV in the low FRS subgroup, but not in the high FRS subgroup. However,
      we did not find any significant main effects of PM2.5 or PM2.5-FRS interactions
      on HRV in city-specified or city-combined analyses. Overall, the findings
      indicate that individual coronary risk profiles may modulate the association
      between particulate air pollution and HRV in high PM exposure levels. 

PMID- 25863506
TI  - Vertical characteristics of PM2.5 during the heating season in Tianjin, China.
AB  - In this study, PM2.5 samples were collected at four heights (10m, 40m, 120m and
      220m) at a meteorological tower in the daytime and nighttime during the heating
      season in Tianjin, China. The vertical variation and diurnal variability of the
      concentrations of PM2.5 and main chemical compositions were analyzed in clear
      days and heavy pollution days. Generally, mass concentrations of PM2.5 and the
      chemical compositions showed a decreasing trend with increasing height, while
      mass percentages of SO4(2-), NO3(-) and OC showed an increasing trend with
      increasing height. Concentrations of ion species and carbon compound in PM2.5
      samples in the daytime were higher than those collected at night, which was due
      to intense human activities and suitable meteorological condition in the daytime.
      The ratios of NO3(-)/SO4(2-) and OC/EC were also considered, and we have observed
      that their levels on heavy pollution days were higher than those on clear days.
      In addition, source apportionments were identified quantitatively using the CMB
      iteration model. The results indicated that contributions of secondary ion
      species increased with increasing height, while contributions of other pollutant
      sources decreased, and contributions of vehicle exhaust were relatively high on
      clear days. 

PMID- 25863507
TI  - Plasma levels of pollutants are much higher in loggerhead turtle populations from
      the Adriatic Sea than in those from open waters (Eastern Atlantic Ocean).
AB  - In this paper we determined the levels of 63 environmental contaminants,
      including organic (PCBs, organochlorine pesticides, and PAHs) and inorganic (As,
      Cd, Cu, Pb, Hg and Zn) compounds in the blood of loggerhead turtles (Caretta
      caretta) from two comparable populations that inhabit distinct geographic areas:
      the Adriatic Sea (Mediterranean basin) and the Canary Islands (Eastern Atlantic
      Ocean). All animals were sampled at the end of a period of rehabilitation in
      centers of wildlife recovery, before being released back into the wild, so they
      can be considered to be in good health condition. The dual purpose of this paper
      is to provide reliable data on the current levels of contamination of this
      species in these geographic areas, and secondly to compare the results of both
      populations, as it has been reported that marine biota inhabiting the
      Mediterranean basin is exposed to much higher pollution levels than that which
      inhabit in other areas of the planet. According to our results it is found that
      current levels of contamination by organic compounds are considerably higher in
      Adriatic turtles than in the Atlantic ones (?PCBs, 28.45 vs. 1.12ng/ml; ?OCPs,
      1.63 vs. 0.19ng/ml; ?PAHs, 13.39 vs. 4.91ng/ml; p<0.001 in all cases). This is
      the first time that levels of PAHs are reported in the Adriatic loggerheads. With
      respect to inorganic contaminants, although the differences were not as great,
      the Adriatic turtles appear to have higher levels of some of the most toxic
      elements such as mercury (5.74 vs. 7.59MUg/ml, p<0.01). The results of this study
      confirm that the concentrations are larger in turtles from the Mediterranean,
      probably related to the high degree of anthropogenic pressure in this basin, and
      thus they are more likely to suffer adverse effects related to contaminants. 

PMID- 25863508
TI  - Evaluation of stream water quality data generated from MODIS images in modeling
      total suspended solid emission to a freshwater lake.
AB  - Modeling of suspended sediment emission into freshwater lakes is challenging due
      to data gaps in developing countries. Existing models simulate sediment
      concentration at a gauging station upstream and none of these studies had modeled
      total suspended solids (TSS) emissions by inflowing rivers to freshwater lakes as
      there are no TSS measurements at the river mouth in the upper Blue Nile basin. In
      this study a 10year TSS time series data generated from remotely sensed
      MODIS/Terra images using established empirical relationship is applied to
      calibrate and validate a hydrology model for Lake Tana in Upper Blue Nile Basin.
      The result showed that at a monthly time scale TSS at the river mouth can be
      replicated with Nash-Sutcliffe efficiency (NS) of 0.34 for calibration and 0.21
      for validation periods. Percent bias (PBIAS) and ratio of the root-mean-square
      error to the standard deviation of measured data (RSR) are all within range.
      Given the inaccessibility and costliness to measure TSS at river mouths to a lake
      the results found here are considered useful for suspended sediment budget
      studies in water bodies of the basin. 

PMID- 25863509
TI  - Dominant mechanisms for the delivery of fine sediment and phosphorus to fluvial
      networks draining grassland dominated headwater catchments.
AB  - Recent advances in monitoring technology have enabled high frequency, in-situ
      measurements of total phosphorus and total reactive phosphorus to be undertaken
      with high precision, whilst turbidity can provide an excellent surrogate for
      suspended sediment. Despite these measurements being fundamental to understanding
      the mechanisms and flow paths that deliver these constituents to river networks,
      there is a paucity of such data for headwater agricultural catchments. The aim of
      this paper is to deduce the dominant mechanisms for the delivery of fine sediment
      and phosphorus to an upland river network in the UK through characterisation of
      the temporal variability of hydrological fluxes, and associated soluble and
      particulate concentrations for the period spanning March 2012-February 2013. An
      assessment of the factors producing constituent hysteresis is undertaken
      following factor analysis (FA) on a suite of measured environmental variables
      representing the fluvial and wider catchment conditions prior to, and during
      catchment-wide hydrological events. Analysis indicates that suspended sediment is
      delivered to the fluvial system predominantly via rapidly responding pathways
      driven by event hydrology. However, evidence of complex, figure-of-eight
      hysteresis is observed following periods of hydrological quiescence, highlighting
      the importance of preparatory processes. Sediment delivery via a slow moving,
      probably sub-surface pathway does occur, albeit infrequently and during low
      magnitude events at the catchment outlet. Phosphorus is revealed to have a
      distinct hysteretic response to that of suspended sediment, with sub-surface
      pathways dominating. However, high magnitude events were observed to exhibit
      threshold-like behaviour, whereby activation and connection of usually
      disconnected depositional zones to the fluvial networks results in the movement
      of vast phosphorus fluxes. Multiple pathways are observed for particulate and
      soluble constituents, highlighting the challenges faced in mitigating the
      delivery of contaminant fluxes to headwater river systems. 

PMID- 25863510
TI  - Audio-visual interactions in environment assessment.
AB  - The aim of the study was to examine how visual and audio information influences
      audio-visual environment assessment. Original audio-visual recordings were made
      at seven different places in the city of Poznan. Participants of the
      psychophysical experiments were asked to rate, on a numerical standardized scale,
      the degree of comfort they would feel if they were in such an environment. The
      assessments of audio-visual comfort were carried out in a laboratory in four
      different conditions: (a) audio samples only, (b) original audio-visual samples,
      (c) video samples only, and (d) mixed audio-visual samples. The general results
      of this experiment showed a significant difference between the investigated
      conditions, but not for all the investigated samples. There was a significant
      improvement in comfort assessment when visual information was added (in only
      three out of 7 cases), when conditions (a) and (b) were compared. On the other
      hand, the results show that the comfort assessment of audio-visual samples could
      be changed by manipulating the audio rather than the video part of the audio
      visual sample. Finally, it seems, that people could differentiate audio-visual
      representations of a given place in the environment based rather of on the sound
      sources' compositions than on the sound level. Object identification is
      responsible for both landscape and soundscape grouping. 

PMID- 25863511
TI  - An integrated approach for monitoring efficiency and investments of activated
      sludge-based wastewater treatment plants at large spatial scale.
AB  - WISE, the Water Information System for Europe, is the web-portal of the European
      Commission (EU) that disseminates the quality state of the receiving water bodies
      and the efficiency of the municipal wastewater treatment plants (WWTPs) in order
      to monitor advances in the application of both the Water Framework Directive
      (WFD) as well as the Urban Wastewater Treatment Directive (UWWTD). With the
      intention to develop WISE applications, the aim of the work was to define and
      apply an integrated approach capable of monitoring the efficiency and investments
      of activated sludge-based WWTPs located in a large spatial area, providing the
      following outcomes useful to the decision-makers: (i) the identification of
      critical facilities and their critical processes by means of a Performance
      Assessment System (PAS), (ii) the choice of the most suitable upgrading actions,
      through a scenario analysis. (iii) the assessment of the investment costs to
      upgrade the critical WWTPs and (iv) the prioritization of the critical facilities
      by means of a multi-criteria approach which includes the stakeholders
      involvement, along with the integration of some technical, environmental,
      economic and health aspects. The implementation of the proposed approach to a
      high number of municipal WWTPs highlighted how the PAS developed was able to
      identify critical processes with a particular effectiveness in identifying the
      critical nutrient removal ones. In addition, a simplified approach that considers
      the cost related to a basic-configuration and those for the WWTP integration,
      allowed to link the critical processes identified and the investment costs.
      Finally, the questionnaire for the acquisition of data such as that provided by
      the Italian Institute of Statistics, the PAS defined and the database on the
      costs, if properly adapted, may allow for the extension of the integrated
      approach on an EU-scale by providing useful information to water utilities as
      well as institutions. 

PMID- 25863512
TI  - Multi-residue analysis of legacy POPs and emerging organic contaminants in
      Singapore's coastal waters using gas chromatography-triple quadrupole tandem mass
      spectrometry.
AB  - A gas chromatography-triple quadrupole mass spectrometry (GC-MS/MS) based method
      was developed for determination of 86 hydrophobic organic compounds in seawater.
      Solid-phase extraction (SPE) was employed for sequestration of target analytes in
      the dissolved phase. Ultrasound assisted extraction (UAE) and florisil
      chromatography were utilized for determination of concentrations in suspended
      sediments (particulate phase). The target compounds included multi-class
      hydrophobic contaminants with a wide range of physical-chemical properties. This
      list includes several polycyclic and nitro-aromatic musks, brominated and
      chlorinated flame retardants, methyl triclosan, chlorobenzenes, organochlorine
      pesticides (OCPs) and polychlorinated biphenyls (PCBs). Spiked MilliQ water and
      seawater samples were used to evaluate the method performance. Analyte recoveries
      were generally good, with the exception of some of the more volatile target
      analytes (chlorobenzenes and bromobenzenes). The method is very sensitive, with
      method detection limits typically in the low parts per quadrillion (ppq) range.
      Analysis of 51 field-collected seawater samples (dissolved and particulate-bound
      phases) from four distinct coastal sites around Singapore showed trace detection
      of several polychlorinated biphenyl congeners and other legacy POPs, as well as
      several current-use emerging organic contaminants (EOCs). Polycyclic and nitro
      aromatic musks, bromobenzenes, dechlorane plus isomers (syn-DP, anti-DP) and
      methyl triclosan were frequently detected at appreciable levels (2-20,000pgL(
      1)). The observed concentrations of the monitored contaminants in Singapore's
      marine environment were generally comparable to previously reported levels in
      other coastal marine systems. To our knowledge, these are the first measurements
      of these emerging contaminants of concern in Singapore or Southeast Asia. The
      developed method may prove beneficial for future environmental monitoring of
      hydrophobic organic contaminants in marine environments. Further, the study
      provides novel information regarding several potentially hazardous contaminants
      of concern in Singapore's marine environment, which will aid future risk
      assessment initiatives. 

PMID- 25863513
TI  - Hydrochemical evolution within a large alluvial groundwater resource overlying a
      shallow coal seam gas reservoir.
AB  - A combination of multivariate statistical techniques, simple hydrochemical mixing
      models and inverse geochemical modelling was used to investigate the major
      hydrochemical evolutionary pathways of a large alluvial aquifer, the upper
      Condamine River alluvium, south-east Queensland, Australia. Hydrochemical
      similarities between alluvium and sedimentary bedrock groundwater imply some
      mixing between alluvial and sedimentary bedrock aquifers, but spatial assessment
      showed that this was localised around outcrops of sedimentary bedrock in upstream
      areas. Within the alluvium, a distinct shift towards a low salinity Na-HCO3 water
      type and a brackish Na-HCO3-Cl water type was obvious in two separate locations.
      Both of these water types are unique to the alluvium, and inverse modelling shows
      that they can evolve via a combination of in situ alluvial processes, including
      diffuse recharge of rainfall or river water or the evolution of basalt-derived
      groundwater via gypsum dissolution plagioclase weathering, cation exchange and
      some carbonate precipitation/dissolution. The evolution of these water types is
      potentially influenced by overlying sodic alkaline soils, and often is associated
      with a source of sulfate. Evapotranspiration is the dominant salinization process
      in the alluvium and increases in calcium cations during salinization indicate
      that brackish Na-HCO3-Cl groundwater in the underlying Walloon Coal Measures are
      unlikely to have a major influence on salinization in the alluvium. The most
      saline water types observed were endemic to shallow zones of the alluvium where
      evapotranspiration is likely. Results demonstrate that a combination of
      multivariate statistics and inverse geochemical modelling can be successfully
      used to delineate hydrochemical pathways in complex hydrogeological settings
      where a range of environmental and anthropogenic factors may be influencing the
      evolution of water types with similar hydrochemical compositions. 

PMID- 25863514
TI  - Effects of laser irradiation at different wavelengths (660, 810, 980, and 1064
      nm) on transient receptor potential melastatin channels in an animal model of
      wound healing.
AB  - The aim of the present study was to compare the effectiveness of four different
      laser wavelengths used for low-level laser therapy(LLLT) on healing of mucositis
      in an animal model of wound healing, by investigating expression of transient
      receptor potential melastatin(TRPM) ion channels. Forty-five rats were
      intraperitoneally injected with 100 mg/kg 5-fluorouracil on day 1 and 65 mg/kg on
      day 3. Superficial scratching on left cheek pouch mucosa was performed on days 3
      and 5. After ulcerative mucositis was clinically detected, LLLT was started (660
      nm, HELBO; 810 nm, Fotona-XD; 980 nm, ARC-Fox; and 1064 nm, Fidelis-Plus3) at 8
      J/cm(2)/day from days 1 to 4. Oval excisional biopsy was performed at the wound
      site, and expression of TRPM2 to TRPM8 was evaluated. Student's t test was used
      for evaluation of significance of TRPM gene expression according to "0" value
      (alpha = 0.05). In 980-nm group, TRPM4, TRPM6, and TRPM7 were significantly
      higher than in the control group (p < 0.005). In 660, 810, and 1064 nm groups,
      only TRPM6 was significantly higher than in control group (p < 0.005). There were
      no significant differences between control and sham groups (p > 0.05). These
      findings suggest that expression of TRPM6 gene was significantly affected by
      irradiation with lasers at different wavelengths, whereas the TRPM4 and TRPM7
      genes were only expressed in the 980-nm diode laser group. TRPM6 gene was highly
      expressed during LLLT, which may lead to accelerated wound healing and tissue
      repair. In contrast, there was some evidence that the 980-nm diode laser caused
      increased expression of TRPM4, TRPM6, and TRPM7 which are responsible for
      stimulation of Ca(2+) and Mg(2+) metabolism, as well as apoptotic pathways of
      controlled cell death. 

PMID- 25863515
TI  - Long-term outcomes of a Web-based diabetes prevention program: 2-year results of
      a single-arm longitudinal study.
AB  - BACKGROUND: Digital therapeutics are evidence-based behavioral treatments
      delivered online that can increase accessibility and effectiveness of health
      care. However, few studies have examined long-term clinical outcomes of digital
      therapeutics. OBJECTIVE: The objective of this study was to conduct a 2-year
      follow-up on participants in the Internet-based Prevent diabetes prevention
      program pilot study, specifically examining the effects on body weight and A1c,
      which are risk factors for diabetes development. METHODS: A quasi-experimental
      research design was used, including a single-arm pre- and post-intervention
      assessment of outcomes. Participants underwent a 16-week weight loss intervention
      and an ongoing weight maintenance intervention. As part of the program,
      participants received a wireless scale, which was used to collect body weight
      data on an ongoing basis. Participants also received A1c test kits at baseline,
      0.5 year, 1 year, and 2-year time points. RESULTS: Participants previously
      diagnosed with prediabetes (n=220) were originally enrolled in the pilot study. A
      subset of participants (n=187) met Centers for Disease Control and Prevention
      (CDC) criteria for starting the program (starters), and a further subset (n=155)
      met CDC criteria for completing the program (completers) and were both included
      in analyses. Program starters lost an average of 4.7% (SD 0.4) of baseline body
      weight after 1 year and 4.2% (SD 0.8) after 2 years, and reduced A1c by mean
      0.38% (SD 0.07) after 1 year and 0.43% (SD 0.08) after 2 years. Program
      completers lost mean 4.9% (SD 0.5) of baseline body weight after 1 year and 4.3%
      (SD 0.8) after 2 years, and reduced A1c by 0.40% (SD 0.07) after 1 year and 0.46%
      (SD 0.08) after 2 years. For both groups, neither 2-year weight loss nor A1c
      results were significantly different from 1-year results. CONCLUSIONS: Users of
      the Prevent program experienced significant reductions in body weight and A1c
      that are maintained after 2 years. Contrary to the expected progression from
      prediabetes to diabetes over time, average A1c levels continued to show an
      average regression from within the prediabetic range (5.7%-6.4%) initially to the
      normal range (<5.7%) after 2 years. Further investigation is warranted to test
      digital therapeutics as a scalable solution to address national diabetes and
      cardiovascular disease prevention efforts.

PMID- 25863516
TI  - Poland's syndrome: an alternative to the 'vascular hypothesis'.

PMID- 25863517
TI  - Fully automated diabetic retinopathy screening using morphological component
      analysis.
AB  - Diabetic retinopathy is the major cause of blindness in the world. It has been
      shown that early diagnosis can play a major role in prevention of visual loss and
      blindness. This diagnosis can be made through regular screening and timely
      treatment. Besides, automation of this process can significantly reduce the work
      of ophthalmologists and alleviate inter and intra observer variability. This
      paper provides a fully automated diabetic retinopathy screening system with the
      ability of retinal image quality assessment. The novelty of the proposed method
      lies in the use of Morphological Component Analysis (MCA) algorithm to
      discriminate between normal and pathological retinal structures. To this end,
      first a pre-screening algorithm is used to assess the quality of retinal images.
      If the quality of the image is not satisfactory, it is examined by an
      ophthalmologist and must be recaptured if necessary. Otherwise, the image is
      processed for diabetic retinopathy detection. In this stage, normal and
      pathological structures of the retinal image are separated by MCA algorithm.
      Finally, the normal and abnormal retinal images are distinguished by statistical
      features of the retinal lesions. Our proposed system achieved 92.01% sensitivity
      and 95.45% specificity on the Messidor dataset which is a remarkable result in
      comparison with previous work. 

PMID- 25863518
TI  - Appearance normalization of histology slides.
AB  - This paper presents a method for automatic color and intensity normalization of
      digitized histology slides stained with two different agents. In comparison to
      previous approaches, prior information on the stain vectors is used in the plane
      estimation process, resulting in improved stability of the estimates. Due to the
      prevalence of hematoxylin and eosin staining for histology slides, the proposed
      method has significant practical utility. In particular, it can be used as a
      first step to standardize appearance across slides and is effective at countering
      effects due to differing stain amounts and protocols and counteracting slide
      fading. The approach is validated against non-prior plane-fitting using synthetic
      experiments and 13 real datasets. Results of application of the method to
      adjustment of faded slides are given, and the effectiveness of the method in
      aiding statistical classification is shown. 

PMID- 25863519
TI  - WM-DOVA maps for accurate polyp highlighting in colonoscopy: Validation vs.
      saliency maps from physicians.
AB  - We introduce in this paper a novel polyp localization method for colonoscopy
      videos. Our method is based on a model of appearance for polyps which defines
      polyp boundaries in terms of valley information. We propose the integration of
      valley information in a robust way fostering complete, concave and continuous
      boundaries typically associated to polyps. This integration is done by using a
      window of radial sectors which accumulate valley information to create WM-DOVA
      (Window Median Depth of Valleys Accumulation) energy maps related with the
      likelihood of polyp presence. We perform a double validation of our maps, which
      include the introduction of two new databases, including the first, up to our
      knowledge, fully annotated database with clinical metadata associated. First we
      assess that the highest value corresponds with the location of the polyp in the
      image. Second, we show that WM-DOVA energy maps can be comparable with saliency
      maps obtained from physicians' fixations obtained via an eye-tracker. Finally, we
      prove that our method outperforms state-of-the-art computational saliency
      results. Our method shows good performance, particularly for small polyps which
      are reported to be the main sources of polyp miss-rate, which indicates the
      potential applicability of our method in clinical practice. 

PMID- 25863520
TI  - Effect of Brief Mindfulness Practice on Self-Reported Affect, Craving, and
      Smoking: A Pilot Randomized Controlled Trial Using Ecological Momentary
      Assessment.
AB  - INTRODUCTION: Despite efficacious pharmacological and behavioral treatments, most
      smokers attempt to quit without assistance and fail to quit. Mindfulness practice
      may be useful in smoking cessation. METHODS: This ecological momentary assessment
      (EMA) study was a pilot parallel group randomized controlled trial of a brief
      mindfulness practice (Brief-MP) intervention on self-reported smoking behavior
      delivered to smokers on a Personal Digital Assistant (PDA) in the field. Adult
      community smokers (N = 44) were randomly assigned to a Brief-MP (n = 24) or
      Control (sham meditation; n = 20) group. Participants were instructed to smoke as
      much or as little as they liked. Participants carried a PDA for 2 weeks and were
      instructed to initiate 20 minutes of meditation (or control) training on the PDA
      daily, completing an assessment of cognitive and affective processes immediately
      afterwards. Additionally, they completed assessments at random times up to four
      times per day. Primary outcome variables were negative affect, craving, and
      cigarettes smoked per day, all self-reported. RESULTS: Thirty-seven participants
      provided EMA data totaling 1874 assessments. Linear Mixed Model analyses on EMA
      data revealed that Brief-MP (vs. Control) reduced overall negative affect, F(1,
      1798) = 13.8, P = .0002; reduced craving immediately post-meditation, (Group *
      Assessment Type interaction, F(2, 1796) = 12.3, P = .0001); and reduced
      cigarettes smoked per day over time (Group * Day interaction, F(1, 436) = 5.50, P
      = .01). CONCLUSIONS: Brief-MP administered in the field reduced negative affect,
      craving, and cigarette use, suggesting it may be a useful treatment.

PMID- 25863521
TI  - "Direct Dripping": A High-Temperature, High-Formaldehyde Emission Electronic
      Cigarette Use Method.
AB  - INTRODUCTION: Electronic cigarettes (ECIGs) electrically heat and vaporize a
      liquid solution to produce an inhalable nicotine-containing aerosol. Normally the
      electrical heater is fed the liquid via an automatic wick system. Some ECIG
      users, however, elect to directly drip liquid onto an exposed heater coil,
      reportedly for greater vapor production and throat hit. Use of such "direct drip
      atomizers" (DDAs) may involve greater exposure to non-nicotine toxicants due to
      the potentially higher temperatures reached by the coil. In this study we
      examined nicotine and volatile aldehyde (VA) emissions from one type of DDA under
      various use scenarios, and measured heater temperature. METHODS: Aerosols were
      machine-generated from an NHALER 510 Atomizer powered by an eGo-T battery
      (Joyetech), using a common PG-based liquid and a fixed puffing regimen. Inter
      drip interval, the number of puffs drawn between replenishing the liquid on the
      coil, was varied from 2-4 puffs/drip. Total particulate matter, nicotine, and VA
      yields were quantified. Heater temperature was monitored using an infrared
      camera. RESULTS: Depending on the condition, VA emissions, including
      formaldehyde, greatly exceeded values previously reported for conventional ECIGs
      and combustible cigarettes, both per puff and per unit of nicotine yield.
      Increasing the inter-drip interval resulted in greater VA emissions, and lower
      total particulate matter and nicotine yields. Maximum heater coil temperature
      ranged from 130 degrees C to more than 350 degrees C. CONCLUSIONS: Due to the
      higher temperatures attained, DDAs are inherently likely to produce high toxicant
      emissions. The diversity of ECIG use methods, including potential off-label
      methods, should be considered as ECIG regulatory efforts proceed.

PMID- 25863522
TI  - Web based listing of agents associated with new onset work-related asthma.
AB  - BACKGROUND: Work-related asthma is common and yet remains a challenge to
      diagnose. Access to a listing of agents associated with work-related asthma has
      been suggested as useful in assisting in the diagnosis. METHODS: The Association
      of Occupational and Environmental Clinics (AOEC) developed criteria that were
      used to review the peer-reviewed medical literature published in English. Based
      on this review, substances were designated either as a sensitizing agent or an
      irritant. The reviews were conducted by a board certified
      internist/pulmonologist/occupational medicine specialist from 2002 to 2007 and a
      board certified internist/occupational medicine physician from 2008- date. All
      reviews were then reviewed by the nine member AOEC board of directors. RESULTS:
      The original list of agents associated with new onset work-related asthma was
      derived from the tables of a text book on work-related asthma. After 13 years of
      review, there are 327 substances designated as asthma agents on the AOEC list;
      173 (52.9%) coded as sensitizers, 35 (10.7%) as generally recognized as an asthma
      causing agent, four (1.2%) as irritants, two (0.6%) as both a sensitizer and an
      irritant and 113(34.6%) agents that still need to be reviewed. CONCLUSIONS: The
      AOEC has developed a readily available web based listing of agents associated
      with new onset work-related asthma in adults. The listing is based on peer
      reviewed criteria. The listing is updated twice a year. Regular review of the
      peer-reviewed medical literature is conducted to determine whether new substances
      should be added to the list. Clinicians should find the list useful when
      considering the diagnosis of work-related asthma.

PMID- 25863523
TI  - 18-year survival of posterior composite resin restorations with and without glass
      ionomer cement as base.
AB  - OBJECTIVE: Advantages and disadvantages of using intermediate layers underneath
      resin-composite restorations have been presented under different perspectives.
      Yet, few long-term clinical studies evaluated the effect of glass-ionomer bases
      on restoration survival. The present study investigated the influence of glass
      ionomer-cement base in survival of posterior composite restorations, compared to
      restorations without base. METHODS: Original datasets of one dental practice were
      used to retrieve data retrospectively. The presence or absence of an intermediate
      layer of glass-ionomer-cement was the main factor under analysis, considering
      survival, annual failure rate and types of failure as outcomes. Other
      investigated factors were: patient gender, jaw, tooth, number of restored
      surfaces and composite. Statistical analysis was performed using Fisher's exact
      test, Kaplan-Meier method and multivariate Cox-regression. RESULTS: In total 632
      restorations in 97 patients were investigated. Annual failure rates percentages
      up to 18-years were 1.9% and 2.1% for restorations with and without base,
      respectively. In restorations with glass-ionomer-cement base, fracture was the
      predominant reason for failure, corresponding to 57.8% of total failures. Failure
      type distribution was different (p=0.007) comparing restorations with and without
      base, but no effect in the overall survival of restorations was found (p=0.313).
      SIGNIFICANCE: The presence of a glass-ionomer-cement base did not affect the
      survival of resin-composite restorations in the investigated sample. Acceptable
      annual failure rates after 18-years can be achieved with both techniques, leading
      to the perspective that an intermediate layer, placed during an interim
      treatment, may be maintained without clinical detriment, but no improvement in
      survival should be expected based on such measure.

PMID- 25863524
TI  - Effect of aerobic exercise training dose on liver fat and visceral adiposity.
AB  - BACKGROUND & AIMS: Aerobic exercise reduces liver fat and visceral adipose tissue
      (VAT). However, there is limited data from randomized trials to inform exercise
      programming recommendations. This study examined the efficacy of commonly
      prescribed exercise doses for reducing liver fat and VAT using a randomized
      placebo-controlled design. METHODS: Inactive and overweight/obese adults received
      8 weeks of either; i) low to moderate intensity, high volume aerobic exercise
      (LO:HI, 50% VO 2peak, 60 min, 4d/week); ii) high intensity, low volume aerobic
      exercise (HI:LO, 70% VO 2peak, 45 min, 3d/week); iii) low to moderate intensity,
      low volume aerobic exercise (LO:LO, 50% VO 2peak, 45 min, 3d/week); or iv)
      placebo (PLA). Liver fat (spectroscopy) and VAT (magnetic resonance imaging) were
      measured before and after intervention. RESULTS: Forty-seven of the 48 (n = 12 in
      each group) participants completed the trial. There were no serious adverse
      events. There was a significant change in group * time interaction in liver fat,
      which reduced in HI:LO by 2.38 +/- 0.73%, in LO:HI by 2.62 +/- 1.00%, and in
      LO:LO by 0.84 +/- 0.47% but not in PLA (increase of 1.10 +/- 0.62%) (p = 0.04).
      There was a significant reduction in VAT in HI:LO (-258.38 +/- 87.78 cm(3)), in
      LO:HI (-386.80 +/- 119.5 cm(3)), and in LO:LO (-212.96 +/- 105.54 cm(3)), but not
      in PLA (92.64 +/- 83.46 cm(3)) (p = 0.03). There were no significant differences
      between the dose or intensity of the exercise regimen and reductions in liver fat
      or VAT (p > 0.05). CONCLUSION: The study found no difference in efficacy of liver
      fat reduction by either aerobic exercise dose or intensity. All of the aerobic
      exercise regimens employed reduced liver fat and VAT by a small amount without
      clinically significant weight loss.

PMID- 25863525
TI  - Exercise and improvement of NAFLD: Practical recommendations.

PMID- 25863526
TI  - The loss of glucose-regulated protein 78 (GRP78) during normal aging or from
      siRNA knockdown augments human alpha-synuclein (alpha-syn) toxicity to rat nigral
      neurons.
AB  - Age-related structural changes and gradual loss of key enzymes significantly
      affect the ability of the endoplasmic reticulum (ER) to facilitate proper protein
      folding and maintain homeostasis. In this work, we present several lines of
      evidence supporting the hypothesis that the age-related decline in expression of
      the ER chaperone glucose-regulated protein 78 (GRP78) could be related to the
      development of Parkinson's disease. We first determined that old (24 months) rats
      exhibit significantly lower levels of GRP78 protein in the nigrostriatal system
      as compared with young (2 months) animals. Then using recombinant adeno-associate
      virus-mediated gene transfer, we found that GRP78 downregulation by specific
      small interfering RNAs (siRNAs) aggravates alpha-synuclein (alpha-syn)
      neurotoxicity in nigral dopamine (DA) neurons. Moreover, the degree of chaperone
      decline corresponds with the severity of neurodegeneration. Additionally,
      comparative analysis of nigral tissues obtained from old and young rats revealed
      that aging affects the capacity of nigral DA cells to upregulate endogenous GRP78
      protein in response to human alpha-syn neurotoxicity. Finally, we demonstrated
      that a sustained increase of GRP78 protein over the course of 9 months protected
      aging nigral DA neurons in the alpha-syn-induced rat model of Parkinson's-like
      neurodegeneration. Our data indicate that the ER chaperone GRP78 may have
      therapeutic potential for preventing and/or slowing age-related
      neurodegeneration.

PMID- 25863527
TI  - White matter integrity in dementia with Lewy bodies: a voxel-based analysis of
      diffusion tensor imaging.
AB  - Many patients with dementia with Lewy bodies (DLB) have overlapping Alzheimer's
      disease (AD)-related pathology, which may contribute to white matter (WM)
      diffusivity alterations on diffusion tensor imaging (DTI). Consecutive patients
      with DLB (n = 30), age- and sex-matched AD patients (n = 30), and cognitively
      normal controls (n = 60) were recruited. All subjects underwent DTI, 18F 2-fluoro
      deoxy-d-glucose, and (11)C Pittsburgh compound B positron emission tomography
      scans. DLB patients had reduced fractional anisotropy (FA) in the
      parietooccipital WM but not elsewhere compared with cognitively normal controls,
      and elevated FA in parahippocampal WM compared with AD patients, which persisted
      after controlling for beta-amyloid load in DLB. The pattern of WM FA alterations
      on DTI was consistent with the more diffuse posterior parietal and occipital
      glucose hypometabolism of 2-fluoro-deoxy-d-glucose positron emission tomography
      in the cortex. DLB is characterized by a loss of parietooccipital WM integrity,
      independent of concomitant AD-related beta-amyloid load. Cortical glucose
      hypometabolism accompanies WM FA alterations with a concordant pattern of gray
      and WM involvement in the parietooccipital lobes in DLB.

PMID- 25863529
TI  - Can serum level of HBsAg differentiate HBeAg-negative chronic hepatitis B from
      inactive carrier state?
AB  - Hepatitis B envelope antigen (HBeAg)-negative hepatitis B virus (HBV) infection
      exerts both inactive carrier (IC) state and chronic hepatitis B (CHB), which are
      sometimes difficult to be differentiated. We aimed to assess the role of
      hepatitis B surface antigen (HBsAg) level in differentiation of CHB and IC among
      a group of chronic HBeAg-negative HBV-infected patients. A total of 251 HBeAg
      negative HBV-infected patients were enrolled. Serum HBV DNA and HBsAg levels were
      determined for each patient. HBV DNA quantification with cutoff value 2000IU/mL
      for diagnosis of CHB had 99.0% sensitivity and 74.1% specificity. A cutoff value
      of HBsAg level at 1000IU/mL was more reliable for diagnosis of CHB with 82.7%
      sensitivity and 66.2% specificity than other HBsAg cutoff values. There was a
      positive correlation between HBV DNA and HBsAg levels in both CHB (r=0.42,
      P<0.001) and IC (r=0.43, P<0.001) groups. Single-point HBsAg quantification did
      not have enough sensitivity and specificity for differentiation of HBeAg-negative
      CHB and IC state. 

PMID- 25863528
TI  - Human tau expression reduces adult neurogenesis in a mouse model of tauopathy.
AB  - Accumulation of hyperphosphorylated and aggregated microtubule-associated protein
      tau (MAPT) is a central feature of a class of neurodegenerative diseases termed
      tauopathies. Notably, there is increasing evidence that tauopathies, including
      Alzheimer's disease, are also characterized by a reduction in neurogenesis, the
      birth of adult neurons. However, the exact relationship between
      hyperphosphorylation and aggregation of MAPT and neurogenic deficits remains
      unclear, including whether this is an early- or late-stage disease marker. In the
      present study, we used the genomic-based hTau mouse model of tauopathy to examine
      the temporal and spatial regulation of adult neurogenesis during the course of
      the disease. Surprisingly, hTau mice exhibited reductions in adult neurogenesis
      in 2 different brain regions by as early as 2 months of age, before the
      development of robust MAPT pathology in this model. This reduction was found to
      be due to reduced proliferation and not because of enhanced apoptosis in the
      hippocampus. At these same time points, hTau mice also exhibited altered MAPT
      phosphorylation with neurogenic precursors. To examine whether the effects of
      MAPT on neurogenesis were cell autonomous, neurospheres prepared from hTau
      animals were examined in vitro, revealing a growth deficit when compared with non
      transgenic neurosphere cultures. Taken together, these studies provide evidence
      that altered adult neurogenesis is a robust and early marker of altered, cell
      autonomous function of MAPT in the hTau mouse mode of tauopathy and that altered
      adult neurogenesis should be examined as a potential marker and therapeutic
      target for human tauopathies.

PMID- 25863530
TI  - Drug-induced lymphocyte stimulation test in the prediction of drug-induced
      hypersensitivity to antituberculosis drugs.
AB  - Antituberculosis (TB) chemotherapeutic drugs may cause a variety of adverse drug
      reactions (ADRs). To assess the potential of drug-induced lymphocyte stimulation
      test (DLST) in screening ADRs in patients treated with anti-TB drugs, we
      performed DLST in 272 TB patients (176 cases with ADRs and 96 controls without
      ADRs) treated with anti-TB drugs isoniazid (INH), rifampicin (RFP), ethambutol
      (EMB), and pyrazinamide (PZA). The ADRs were diagnosed by drug provocation test
      based on clinical and laboratory examinations. The sensitivities of DLST in the
      diagnosis of INH-, RFP-, EMB-, or PZA-induced ADRs were 57.8%, 37.1%, 42.4%, and
      23.1%, respectively, with the corresponding specificities being 93.4%, 94.0%,
      97.5%, and 98.8%. DLST has high specificity and limited sensitivity in the
      diagnosis of anti-TB drug-induced ADRs. In combination with clinical observation
      and drug use history, DLST could have a predictive validity of ADRs, especially
      when a positive result is obtained. 

PMID- 25863531
TI  - Gastroesophageal reflux in laparoscopic sleeve gastrectomy: hiatal findings and
      their management influence outcome.
AB  - BACKGROUND: Sleeve gastrectomy (SG) has become a definitive treatment for morbid
      obesity. There is conflicting evidence on the effects of SG on gastroesophageal
      reflux disease (GERD). OBJECTIVE: The objective of this study was to assess
      whether taking an aggressive approach to managing hiatal weakness in patients
      undergoing SG results in an alteration in GERD symptoms. SETTING: Tertiary public
      hospital and private hospital, Sydney, Australia. METHODS: Patients undergoing
      laparoscopic extended (beginning within 2 cm from pylorus) SG were included. If
      evidence of weakness was present, an anterior hiatal dissection and tight suture
      repair was performed. If a hiatus hernia was present, formal repair was
      undertaken. Patients were questioned and scored on preoperative and postoperative
      reflux symptom frequency and severity, proton pump inhibitor (PPI) usage, current
      weight, and satisfaction. RESULTS: A continuous cohort of 262 patients
      experienced a significant reduction in heartburn frequency (P = .035) and
      severity (P = .017). Moderate/severe preoperative reflux (Visick score 3 and 4)
      often improved whether there was a defect requiring repair or not (no repair P =
      .02, hiatal suture P = .001, hiatus hernia repair P<.001). The severity of
      symptoms also improved (no repair P = 0.005, hiatal suture P<.001, hiatus hernia
      repair P< .001). CONCLUSION: Moderate or severe preexisting gastroesophageal
      reflux improved for most of our obese patients undergoing an extended SG when
      hiatal defects were routinely repaired. Moderate to severe preoperative reflux
      also improved in the average obese patient when there was no hiatal defect to
      repair.

PMID- 25863532
TI  - Strategies for managing oxygenation in obese patients undergoing laparoscopic
      surgery.
AB  - The worldwide trend toward increasing body mass index (BMI) has caused the
      anesthetic management of overweight, obese, and severely obese patients to become
      common. The increase in oxygen demand coupled with the anatomic and physiologic
      changes associated with excess adipose tissue make maintenance of oxygenation a
      major challenge during induction, maintenance and recovery from general
      anesthesia. It is crucial for anesthesiologists, surgeons and perioperative
      healthcare providers alike to have a thorough understanding of the impact of
      airway management and mechanical ventilation on the respiratory care of the obese
      in the immediate perioperative setting. In this manuscript we aim to discuss the
      consequences of obesity, particularly abdominal obesity, on respiratory
      physiology and provide suggestions on intraoperative ventilatory strategies to
      maintain oxygenation in the severely obese patient undergoing pneumoperitoneum. 

PMID- 25863533
TI  - Is sleeve gastrectomy still contraindicated for patients aged>=60 years? A case
      matched study with 24 months of follow-up.
AB  - BACKGROUND: Current guidelines consider that bariatric surgery is relatively
      contraindicated in elderly adults (aged>=60 years). The objective of this study
      was to evaluate obesity-related morbidity after sleeve gastrectomy (SG) according
      to whether patients were aged>=60 years or<60 years. METHODS: Forty-two patients
      aged>=60 years (the elderly group) were matched 1:2 with 84 patients aged<60 (the
      control group). The primary objective was to compare weight change and the
      remission rate of co-morbidities in the 2 groups after 24 months of follow-up.
      The secondary endpoints were short-term and midterm postoperative outcomes
      (operating time, the frequency of conversion to laparotomy, the length of
      hospital stay, postoperative complications, mortality, and the SG failure rate).
      RESULTS: No significant differences were observed between the elderly and control
      groups in terms of the mean operating time (83 minutes in both groups; P = .90),
      length of stay (3.2 versus 3.4 days, respectively; P = .51), morbidity rate (4.7%
      versus 9.5%, P = .35), or mortality rate (0% in both groups). The mean excess
      weight loss was significantly lower in the elderly group than in the control
      group at 12 months (56.2% versus 71.4%, respectively; P<.01) and 24 months (51.8%
      versus 73.5%, P<.01). Similar statistically significant differences were observed
      between the elderly group and control group for remission of metabolic syndrome
      (95% versus 90%, respectively; P = .55), type 2 diabetes mellitus (87% versus
      71%, respectively; P = .13), hypertension (81% versus 77%, respectively; P =
      .71), and dyslipidemia (94% versus 74%, respectively; P = .09) at 24 months after
      SG. CONCLUSION: Results support the safety and efficacy of SG for morbid obesity
      in patients aged>=60 years. In contrast to weight loss, the long-term morbidity
      rate and remission of obesity-related co-morbidities were similar in the
      participants aged>=60 years and those aged<60 years.

PMID- 25863534
TI  - Comment on: Bariatric surgery outcomes in patients with systemic lupus
      erythematosus.

PMID- 25863535
TI  - Impact of perioperative management of glycemia in severely obese diabetic
      patients undergoing gastric bypass surgery.
AB  - BACKGROUND: Roux-en-Y gastric bypass (RYGB) surgery is associated with rapid
      postsurgical improvement in glycemic control in patients with type 2 diabetes
      mellitus (T2 DM). However, there is little outcome-based evidence to guide the
      glycemic management of this patient group preoperatively. OBJECTIVES: We
      conducted 2 pilot studies randomizing patients to assess the impact of intensive
      glucose management pre- and post-RYGB on clinical outcomes after surgery.
      SETTING: University hospital. METHODS: In the GLUCOSURG-pre randomized controlled
      trial (RCT), 34 obese T2 DM patients with glycated hemoglobin (HbA1 c) >=8.5% (69
      mmol/mol) undergoing RYGB were randomly assigned to receive either glucose
      optimization or no optimization 3 months preoperatively. In the GLUCOSURG-post
      RCT, 35 obese T2 DM patients on insulin were randomly assigned to either
      intensive or conservative glucose management up to 2 weeks post- RYGB. HbA1c at 1
      year post-RYGB was the primary outcome. RESULTS: In GLUCOSURG-pre, the HbA1 c at
      1 year postsurgery was -3.0% (51.9 mmol/mol) in the optimized and -4.0% (45.4
      mmol/mol) in the nonoptimized groups (P = .06). In GLUCOSURG-post, there were no
      significant differences in HbA1 c at 1 year postsurgery between the intensive and
      conservative groups [-2.4% (44.3 mmol/mol)] versus [-2.3% (44.3 mmol/mol), P =
      .73)]. CONCLUSIONS: Our pilot studies suggested that neither intensive management
      of glycemia in the 3 months pre- RYGB, nor the first 2 weeks post-RYGB resulted
      in better glycemic control one year after surgery. RYGB has substantial effects
      on glucose control, and additional intensive glucose-lowering interventions do
      not confer clinical benefits compared to conservative approaches.

PMID- 25863536
TI  - Correlation between the Beck Depression Inventory and bariatric surgical
      procedures.
AB  - BACKGROUND: The Beck Depression Inventory (BDI) is a psychosocial screen for
      depression in obese patients seeking bariatric surgery. Gastric bypass improves
      postsurgical BDI scores due to weight loss, which predicts future weight loss.
      The effect of different bariatric procedures with differences in weight loss on
      BDI scores is unknown. OBJECTIVE: To evaluate the relationship between different
      bariatric procedures and changes in the BDI scores, adjusting for the initial BDI
      score, and to consider the impact of psychosocial variables. The secondary
      objective was to assess the relationship between changes in BDI scores and weight
      loss at 6 to 12 months. SETTING: University Hospital, United States. METHODS:
      Bariatric surgical patients were prospectively enrolled and retrospectively
      reviewed. We assessed changes in BDI after adjusting for the presurgical BDI and
      analyzed the relationship between patient demographic
      characteristics/psychological disorders and changes in BDI. RESULTS: We enrolled
      137 patients who underwent a gastric band procedure, sleeve gastrectomy, or
      gastric bypass. We found a significant decrease in BMI and BDI scores across the
      full sample. Unlike BDI, change in BMI varied with procedure. Normalizing for
      baseline BDI, change in BDI did not significantly correlate with change in BMI.
      Patients who were employed and those without psychiatric history experienced even
      greater improvement in BDI scores. No statistically significant correlation was
      found between the change in BDI and weight loss at 6-12 months. CONCLUSIONS: BDI
      scores were independent of the type of bariatric procedure and the amount of
      weight loss. Advantageous psychosocial parameters were associated with greater
      improvement in BDI scores.

PMID- 25863537
TI  - Indications and outcomes of reversal of Roux-en-Y gastric bypass.
AB  - BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (RYGB) is proven to be a safe
      and effective treatment of obesity and related co-morbidities. However, there is
      a small group of patients who are unable to tolerate postoperative complications
      and ultimately undergo reversal procedures. This study demonstrates indications
      and postoperative outcomes in 8 patients following RYGB reversal. METHODS:
      Retrospective review of 8 patients who required RYGB reversal between July 2009
      to October 2013. Data points included demographic characteristics, body mass
      index (BMI), co-morbidities, reasons for reversal and postoperative outcomes.
      RESULTS: All patients were female with a mean age of 44.5 +/- 8.8 years (range,
      35-63) and BMI of 30.0 +/- 9.8 kg/m(2) (range, 19.3-43.8) before reversal.
      Reasons for reversal included recurrent anastomotic ulcer (n = 3), intractable
      nausea and emesis (n = 3), hypocalcemia (n = 1), and neuroglycopenia (n = 1).
      Mean period from RYGB to reversal was 127.8 +/- 95.4 months (range, 21-298) and
      mean length of hospital stay following reversal was 5.1 +/- 3.0 days (range, 2
      11). One patient was lost to follow-up. Mean BMI at the last visit was 37.3 +/-
      12.6 kg/m(2) (range, 24.0-56.5). Two patients (28.6%) maintained the same weight
      9 and 11 months after reversal. One returned to her pre-RYGB weight and 4
      patients gained some of their weight back after reversal. Three (37.5%) patients
      required readmissions for abdominal pain and nausea/vomiting, and no patients
      required reoperations following RYGB reversal. CONCLUSIONS: Reversal of RYGB to
      normal anatomy is reasonable in patients with severe or refractory complications.

PMID- 25863538
TI  - Trocar site hernia after laparoscopic sleeve gastrectomy using a specific open
      laparoscopy technique.
AB  - BACKGROUND: Obesity is recognized as a risk factor for trocar site hernia (TSH)
      after laparoscopic surgery. Some recent studies have reported a TSH rate after
      bariatric surgery ranging from 0% to 1.6% using clinical evaluation and may
      underestimate the TSH rate. The objective of this study was to evaluate the TSH
      rate after sleeve gastrectomy (SG) by abdominal computed tomography (CT) scan.
      METHODS: A retrospective review of all patients who underwent first-line SG and
      abdominal CT scan between March 2004 and February 2014 was performed. The primary
      endpoint was the incidence of TSH. Secondary endpoints were the site of TSH, the
      TSH rate with open laparoscopy using the authors' technique, and risk factors for
      TSH after SG. RESULTS: During the period study, 1108 patients underwent first
      line SG, including 10 cases of conversion to laparotomy (excluded from the
      present analysis). Of the remaining patients, 228 had abdominal CT scan (20.7%),
      with a mean age of 45.1 years (18-68 yr) and a mean BMI of 47.6 kg/m(2) (33-75.4
      kg/m(2)). The median time interval between SG and CT scan was 27 months (3-92
      mo). CT scan revealed 44 TSH in 43 patients (18.8%). The site of the TSH was
      epigastric (16.6%), open laparoscopy (1.7%), right subcostal margin (0.8%), with
      no TSH in the left subcostal margin. In patients with>1 year of follow-up, the
      TSH rate was 19.7%. CONCLUSION: The TSH rate after bariatric surgery is
      underestimated. The authors' open laparoscopy technique is a reliable technique
      with a low TSH rate. In the light of these results, the epigastric trocar site is
      systematically closed at the end of SG.

PMID- 25863540
TI  - Predicting postoperative day 1 hematocrit levels after uncomplicated
      hysterectomy.
AB  - OBJECTIVE: To develop a model for predicting postoperative hematocrit levels
      after uncomplicated hysterectomy. METHODS: In a retrospective study, data were
      analyzed from the Michigan Surgery Quality Collaborative for non-emergent
      hysterectomies performed for benign indications among women aged at least 18
      years between January 1, 2012, and April 4, 2014. Linear mixed models were used
      for univariate and multivariate analyses. RESULTS: The model was developed with
      data from 4747 hysterectomies and validated on 1184 cases. In the mixed
      multivariate analysis, higher postoperative day 1 (POD1) hematocrit levels were
      associated with higher weight (B=0.03222, P<0.001), higher preoperative
      hematocrit (B=0.6587, P<0.001), and non-vaginal hysterectomy (B=0.2815,
      P=0.0055). Lower POD1 hematocrit was associated with higher preoperative platelet
      count (B=-0.00457, P<0.001), greater estimated blood loss (B=-0.00652, P<0.001),
      and larger intraoperative crystalloid volume (B=-0.3303, P<0.001). The final
      model predicted POD1 hematocrit within 4% points of the actual value for 91.7% of
      cases in the validation set. CONCLUSION: Use of the model after uncomplicated
      hysterectomy might help to support the practice of selectively conducting
      postoperative hematocrit tests after hysterectomy in a clinically thoughtful and
      cost-effective manner.

PMID- 25863539
TI  - The long non-coding RNA HNF1A-AS1 regulates proliferation and metastasis in lung
      adenocarcinoma.
AB  - Long noncoding RNAs (lncRNAs) have emerged as key regulators of tumor development
      and progression. The lncRNA HNF1A-antisense 1 (HNF1A-AS1) is a 2455-bp transcript
      on chromosome 12 with a potential oncogenic role in esophageal adenocarcinoma.
      Nevertheless, current understanding of the involvement of HNF1A-AS1 in lung
      adenocarcinoma tumorigenesis remains limited. In this study, we analyzed the
      roles of HNF1A-AS1 in 40 lung adenocarcinoma tissues and five lung cancer cell
      lines. Our results showed that HNF1A-AS1 was significantly up-regulated in lung
      adenocarcinoma tissues compared with corresponding non-tumor tissues, and its
      expression level was significantly correlated with TNM stage, tumor size, and
      lymph node metastasis. The UCSC Cancer Genomics Browser's Kaplan-Meier plot
      suggested that patients in the high HNF1A-AS1 expression subgroup experienced
      worse overall survival compared to the low expression subgroup. Moreover, HNF1A
      AS1 was determined to promote tumor proliferation and metastasis, both in vitro
      and in vivo, by regulating cyclin D1, E-cadherin, N-cadherin and beta-catenin
      expression. In addition, the binding of HNF1A-AS1 to DNMT1 may explain its
      regulation of E-cadherin. In conclusions, we demonstrated that increased HNF1A
      AS1 expression could regulate cell proliferation and metastasis and identified it
      as a poor prognostic biomarker in lung adenocarcinoma. 

PMID- 25863541
TI  - A meta-analysis of maternal and fetal outcomes of pregnancy after bariatric
      surgery.
AB  - BACKGROUND: The effects of bariatric surgery (BS) on outcomes in subsequent
      pregnancies are unclear. OBJECTIVES: To compare maternal and fetal outcomes among
      women who become pregnant after BS and obese women who have not undergone BS
      before pregnancy. SEARCH STRATEGY: PubMed and Embase were searched for relevant
      reports, and the reference lists of identified articles were hand-searched.
      SELECTION CRITERIA: Cohort studies that compared outcomes among women who had
      undergone any type of BS and obese women who had not undergone surgery were
      included when results were reported as risk ratios or odds ratios (ORs). DATA
      COLLECTION AND ANALYSIS: Summary ORs were estimated using a random effects model.
      MAIN RESULTS: Eleven studies were included. Compared with obese women who had not
      undergone BS, women who had undergone BS had significantly lower odds of
      gestational diabetes (OR 0.31; 95% CI 0.15-0.65), hypertensive disorders (OR
      0.42; 95% CI 0.23-0.78), and macrosomia (OR 0.40; 95% CI 0.24-0.67). However,
      their odds of small-for-gestational-age newborns were increased (OR 2.16; 95% CI
      1.28-3.66). No significant differences were recorded for cesarean, postpartum
      hemorrhage, and preterm delivery. CONCLUSIONS: BS reduces the odds of some
      adverse maternal and fetal outcomes among obese women.

PMID- 25863542
TI  - Three-week or one-week bladder catheterization for hypospadias repair? A
      retrospective-prospective observational study of 189 patients.
AB  - PURPOSE: While there is little scientific evidence over the optimal duration for
      transurethral bladder catheterization after hypospadias repair, most surgeons
      leave the catheter for 7-10 days. We herein describe our experience with bladder
      catheterization for three weeks after hypospadias repair, an approach not
      previously described in the literature. PATIENTS AND METHODS: We reviewed the
      charts of 189 patients who underwent hypospadias repair by a single pediatric
      urologist. The study population was divided as follows: group 1 consisted of
      children operated between March 2007 and September 2010 and whose catheters were
      left for one week (n=95); group 2 consisted of those operated between September
      2010 and July 2013 and whose catheters were left for three weeks (n=94). The
      primary objective of the study was to compare complication rates between the two
      groups. Secondary outcomes were evaluation of the effect of age, surgical
      technique, curvature, and hypospadias degree as potential factors for
      postoperative complications. RESULTS: Median age at hypospadias repair was 18
      months (range, 3-100 months) in group 1, and 16 months (range, 2-96 months) in
      group 2, P=.209. The complication rate was 22.1% (n=21) for group 1 and 7.4%
      (n=7) for group 2, P=.005. Complications observed in group 1 and 2 were meatal
      stenosis (n=4 and 2, respectively) and urethro-cutaneous fistulas (n=17 and 5,
      respectively). Coronal fistulas manifested more frequently in patients in group 1
      compared to those in group 2 (13.7% vs. 3.2%, P=.01). Complications were observed
      in 20 patients out of 139 (11.5%) after Duplay, and in 8 patients out of 15
      (53.3%) after Duckett (P<.001). In Duplay cases, complications were significantly
      associated with one-week bladder catheterization (OR: 5.00; 95% CI: 1.53-16.32;
      P=.008) and higher age group at operation (OR: 1.88; 95% CI 1.07-3.28; P=.026).
      In Duckett cases, number of surgeries, age, severity, curvature and catheter
      duration were not found to be associated with complications. CONCLUSION: In cases
      of Duplay, a three-week instead of one-week catheterization and age below 6
      months at hypospadias repair are associated with a better outcome and fewer
      complications.

PMID- 25863543
TI  - Prenatally diagnosed neck masses: long-term outcomes and quality of life.
AB  - PURPOSE: To determine long-term outcomes of fetuses with neck masses (NM),
      including functional and cosmetic results. METHODS: A retrospective review was
      performed of all fetuses evaluated for NM from November 2001 to March 2014.
      Quality of life (QOL) was evaluated using the validated PedsQLTM questionnaire.
      RESULTS: Of 35 fetuses evaluated, 9 died perinatally and 1 died late from
      tracheostomy complications. NM ranged from 4 to 20cm (mean, 9.1cm); 18 were
      delivered by EXIT. Of 25 surviving patients, 22 had mass resection, 7 requiring
      more than one procedure. Surviving patients with lymphatic malformations (LM) had
      the highest incidence of moderate and severe disfigurement and a higher rate of
      persistent/recurrent disease (100% vs. 31%, p=0.002) and cranial nerve
      dysfunction (50% vs. 0%, p=0.005) compared to those with non-LM diagnoses. Of 9
      children attending school, 78% achieve grades of A/B's. QOL for 13 patients
      revealed a mean score of 83/100 for physical and 78/100 for psychosocial
      functioning. Median follow-up was 6 years (7 months-17 years). CONCLUSION: Unlike
      those with teratoma or other lesions, children with congenital cervicofacial LM
      are at high-risk for persistent disease, nerve dysfunction and moderate-severe
      disfigurement. There is substantial perinatal morbidity for fetuses with neck
      masses, but for those surviving, the long-term functional and cognitive outcomes
      are good.

PMID- 25863544
TI  - Ultrasound-guided hydrostatic reduction of intussusception with saline: Safe and
      effective.
AB  - PURPOSE: The study was undertaken to assess the efficacy of ultrasound-guided
      saline enema in reducing intussusception and to determine the role of age and
      duration of symptoms on this event. METHODS: The case records of patients who
      were treated for intussusception at our institutions over the past 10 years were
      retrospectively analyzed. A total of 419 patients were treated for
      intussusception and 375 of them were included into the study. Patients were
      excluded if they had symptoms and signs of acute abdominal disease and required
      surgery as an initial treatment. RESULTS: Hydrostatic reduction was successful in
      313 of the 375 patients (83.46%). The procedure-related complication rate was
      nil. There were 29 episodes of recurrences in 23 patients, and recurrence rates
      did not differ between patients who responded to hydrostatic reduction and those
      who required surgery. Younger age [median (range); 11 months (3-108 months) vs.
      20 months (1-180 months); p<0.05], rectal bleeding (p<0.01) and long duration of
      symptoms [mean (range); 1.95 days (1-7 days) vs. 1.44 days (1-10 days); p<0.01]
      were significantly associated with failed hydrostatic reduction. CONCLUSION:
      Ultrasound-guided hydrostatic reduction is an easy, safe and effective method for
      the treatment of intussusception in the absence of acute abdominal findings.

PMID- 25863545
TI  - Long-term outcomes of ileal pouch-anal anastomosis for pediatric chronic
      ulcerative colitis.
AB  - BACKGROUND: Ileal pouch-anal anastomosis (IPAA) is the surgical treatment of
      choice for patients with chronic ulcerative colitis (CUC). In the pediatric
      population, short-term outcomes of IPAA are excellent but long-term data limited.
      The purpose of this study is to report long-term functional and quality of life
      outcomes of IPAA in pediatric patients. METHODS: Functional outcomes and quality
      of life (QoL) following IPAA in patients <= 18 years of age were prospectively
      assessed by survey over a 30 year period. Preoperative information, chronic
      pouchitis and pouch loss were retrospectively reviewed. RESULTS: Over 30 years,
      202 children with CUC underwent IPAA. Questionnaires were returned by 87% and
      median (range) survey follow-up was 181.5 (7.8-378.5) months. Postoperative day
      and night-time stool frequency did not increase over time though incontinence
      increased slightly. Quality of life (QoL) was generally excellent and stable over
      time. Crohn's disease (CD) was diagnosed in 33 (16%) patients during the follow
      up period. Chronic pouchitis occurred in 22 patients and pouch failure in 13
      patients. Kaplan Meier estimates of pouch survival at 20 years were 61% for
      patients with CD and 92% for CUC. CONCLUSIONS: Ileal pouch-anal anastomosis has
      long-term durability as a cure for pediatric chronic ulcerative colitis, with
      most patients reporting stable bowel function and QoL. Chronic pouchitis and
      pouch failure affect a minority of patients and require further study.

PMID- 25863546
TI  - Pediatric patients transferred for operative management of appendicitis: are they
      at a disadvantage?
AB  - PURPOSE: Many pediatric patients are initially diagnosed with appendicitis at
      referring hospitals and are subsequently transferred to pediatric facilities. We
      aimed to compare outcomes of patients transferred to a pediatric referral center
      to those who present primarily for operative management of appendicitis. METHODS:
      A retrospective review of 326 patients with operative appendicitis from July 2012
      to July 2013 was performed. Demographic data, clinical parameters, and outcomes
      were analyzed. RESULTS: Transferred (n=222, 68%) and primary patients (n=104,
      32%) were similar except for mean age (primary 12.4 vs. transferred 11.2 years,
      p<0.01). Computed tomography scans were performed in 80% of transferred compared
      to 40% of primary patients. Primary patients were more likely to present between
      the hours of 09:00 and 17:59 (52%), while transferred arrived equally across all
      hours. Both groups were more likely to present with acute appendicitis (primary
      56% vs. transfer 61%, p=NS). There was no difference in time of diagnosis to time
      of appendectomy, length of hospital stay, or 30 day complications (primary 8.6%
      vs. transfer 5.8%, p=NS). CONCLUSIONS: Patients transferred for definitive care
      of appendicitis are not found to have more advanced disease or have increased
      complications; however, they are exposed to significantly more ionizing radiation
      during evaluation for appendicitis.

PMID- 25863547
TI  - Innovative clinical and public health strategies to promote adolescent
      vaccination.

PMID- 25863548
TI  - Keen on teen vaccines: improvement of adolescent vaccine coverage in rural North
      Carolina.
AB  - PURPOSE: To improve adolescent immunization coverage in a rural North Carolina
      county. METHODS: Adolescent immunization coverage rates in an intervention and
      four comparison counties were compared over 1 year. We introduced practice-based
      interventions in seven practices centering on immunization registry-driven recall
      of adolescents for immunizations with postcard reminders (Phase 1), and 6 months
      later employed nontargeted school-generated telephone reminders to parents of
      adolescents (Phase 2). RESULTS: Improvements in the intervention county among 11-
      to 12-year-olds occurred for first-dose human papillomavirus vaccine in both boys
      (overall change, 14.2%-32.1%) and girls (27.4%-43.4%) and the meningococcal
      vaccine (34.6%-49.4%). Improvements among adolescents 13-18 years were limited to
      human papillomavirus vaccine completion in boys (1.6%-4.2%). Improvements were
      greater during Phase 1 than Phase 2 and among younger adolescents. Coverage
      improvements in the comparison counties were smaller than those observed in the
      intervention county. CONCLUSIONS: A resource-light two-phase intervention led to
      modest improvements in immunization coverage, most notably in the largest
      adolescent practice in the county, and suggested potential for further gains,
      particularly among younger adolescents.

PMID- 25863549
TI  - Effectiveness of centralized text message reminders on human papillomavirus
      immunization coverage for publicly insured adolescents.
AB  - PURPOSE: We evaluated a managed care organization (MCO)-generated text message
      reminder-recall system designed to improve human papillomavirus (HPV) vaccination
      coverage. METHODS: We conducted a randomized controlled trial of text reminder
      recall for parents of 3,812 publicly insured adolescents aged 11-16 years with no
      prior HPV vaccinations who were enrolled in a single MCO and were patients at one
      of 39 primary care practices. We determined the rate of HPV receipt for
      intervention versus control with the Kaplan-Meier failure function and determined
      hazard ratios using a clustered stratified Cox model, clustering on primary care
      provider and stratified on practice. We examined results for all subjects, and
      for those with a valid phone number, stratified by age group (11-13 years and 14
      16 years) and gender. A post hoc analysis included all subjects and controlled
      for age and gender. RESULTS: HPV dose 1 vaccination rates were not significantly
      different when all participants were included, but for the subset of parents
      (54%) able to receive messages, HPV dose 1 rates were 13% for the control group
      and 16% for the intervention group; hazard ratio, 1.3 (95% confidence interval,
      1.0-1.6; p = .04), when controlling for age and gender. There were no significant
      findings in the analysis stratified by age and gender. CONCLUSIONS: MCO-based
      text reminders are feasible and have a modest effect on HPV dose 1 vaccination
      rates for those parents able to receive text messages with valid phone numbers in
      the MCO database. Future studies should examine a similar intervention for those
      parents who already accepted the first HPV vaccine dose.

PMID- 25863550
TI  - Direct messaging to parents/guardians to improve adolescent immunizations.
AB  - PURPOSE: To study the impact on adolescent immunization rates of direct messages
      to parents/guardians. METHODS: Electronic health record rules identified
      adolescents needing an immunization. Parents/guardians of adolescents were
      messaged via a single vendor using automated text, prerecorded voice, and/or
      postcard. RESULTS: Parents/guardians of 3,393 patients, ages 11-18 years, with
      one or more primary care visits in the prior 2 years, identified as needing
      (average of 2.04 years) a vaccination (meningococcal conjugate, human
      papillomavirus, or tetanus, diphtheria, and pertussis vaccines) were messaged
      (mean age, 14 years; 50% male; 38% African-American; 23% white; 19% Hispanic; and
      79% public health insurance). A total of 7,094 messages were sent: 3,334
      automated voice (47%), 2,631 texts (37%), and 1,129 postcards (16%). After the
      first message, 865 adolescents (25.5%) received at least one vaccine. Within 24
      weeks of messaging 1,324 vaccines (745 human papillomavirus; 403 meningococcal
      conjugate; and 176 tetanus, diphtheria, and pertussis vaccines) occurred in 959
      visits (83.8% physician visits and 16.2% nurse visits). Average visits generated
      $204 gross reimbursement for $1.77 in messaging expenses per vaccine given. No
      differences in immunization completion rates occurred by age, gender,
      race/ethnicity, or insurance type. At 24 weeks, one message was more effective
      than two or three messages (35.6%, 19.4%, and 24.1% effectiveness, respectively;
      p < .0001). Texts and postcards correlated with more vaccination visits (38.8%
      and 40.1%, respectively) than phone calls (31.5%; p = .04). More vaccines due led
      to increasing message effectiveness. CONCLUSIONS: Automated texts, voice
      messages, and postcards had a significant positive effect on vaccination rates in
      adolescents needing vaccination and required minimal financial expenditure.

PMID- 25863551
TI  - Comparison of reminder methods in selected adolescents with records in an
      immunization registry.
AB  - PURPOSE: The aim of this study was to assess the effectiveness and cost
      efficiency of three reminder/recall methods for improving adolescent vaccination
      rates using the San Diego Immunization Registry. METHODS: Parents of 5,050
      adolescents whose records indicated they lacked one or more adolescent vaccines
      were identified from the San Diego Immunization Registry and contacted by
      telephone. Based on their preference, consenting participants were enrolled to
      receive either postal mail (n = 282), e-mail (n = 963), or text (n = 552)
      reminders for vaccination. The intervention groups were sent a series of up to
      three reminders. The vaccination completion rate was compared between the
      intervention groups and two control groups-the enrollment phone call-only group
      who declined to participate and a no contact group-using logistic regression.
      RESULTS: The participants who received any reminder were more likely (24.6% vs.
      12.4%; p < .001) to become up-to-date (UTD) than those in the enrollment phone
      call-only group. At the conclusion of the study observation, UTD status was
      reached by 32.1% of text message recipients, 23.0% of postcard recipients, and
      20.8% of e-mail recipients compared to 12.4% for the enrollment phone call
      recipients. Only 9.7% of nonintervention adolescents became UTD. CONCLUSIONS: All
      three reminder interventions were effective in improving adolescent vaccination
      rates. Although postal mail reminders were preferred by most participants, text
      messaging and e-mail were the more effective reminder methods. Text messaging and
      e-mail as reminder methods for receiving vaccinations should be considered for
      use to boost vaccination completion among adolescents.

PMID- 25863552
TI  - Interventions to improve adolescent vaccination coverage.

PMID- 25863553
TI  - Trust and a school-located immunization program.
AB  - PURPOSE: To determine variables associated with parental trust in a school
      located immunization program (SLIP) and the effect of trust-building
      interventions on trust and participation in SLIPs. METHODS: Parents among eight
      schools randomized to a trust-building intervention or a control condition (four
      schools each) completed a five-item trust survey before SLIP implementation both
      in year 1 (fall 2012) and in year 2 (fall 2013). Mean trust scores were
      calculated. Associations between baseline demographic and experiential variables
      and mean trust scores were analyzed. Mean trust scores in intervention and
      control schools were compared before SLIP in years 1 and 2, and SLIP
      participation rates were noted. RESULTS: From year 1, 1,608 parent surveys were
      analyzed. Baseline mean trust score across schools was 3.59 of 5 (5 = highest
      trust). In a multiple linear regression model, annual household income, survey
      language version, participation in a previous SLIP, child's health insurance
      status, and perceived vaccine importance were significantly associated with
      parental trust in SLIPs (R(2)= .06, p < .001). There was no difference in mean
      trust scores between intervention and control schools (p = .8). In year 2, 844
      surveys were analyzed, and a modest difference was observed between intervention
      and control schools (mean trust score = 3.66 and 3.57, respectively, p = .07).
      SLIP participation rates appeared higher in intervention (7.7%) versus control
      schools (4.3%) in year 1. CONCLUSIONS: Baseline trust in SLIPs among a low
      income, largely Hispanic group of parents in Texas was moderately high. Factors
      associated with trust included demographic and experiential variables, and
      interventions aimed at increasing parents' perception of vaccine importance and
      participation in SLIPs may be effective in increasing parental trust in SLIPs.

PMID- 25863554
TI  - Increasing human papillomavirus vaccine initiation among publicly insured Florida
      adolescents.
AB  - PURPOSE: We evaluated the feasibility of a multilevel intervention to increase
      the human papillomavirus (HPV) vaccine initiation among adolescents. METHODS: We
      used a four-arm factorial, quasi-experimental trial to assess feasibility and
      short-term, preliminary effectiveness of a health system-level, gender-specific
      postcard campaign and an in-clinic health information technology (HIT) system.
      Between August and November 2013, we tested the intervention among 11- to 17-year
      olds without prior HPV vaccine claims in the Florida Medicaid or Children's
      Health Insurance Program encounters (2,773 girls and 3,350 boys) who attended or
      were assigned to primary care clinics in North Central Florida. RESULTS: At least
      one postcard was deliverable to 95% of the parents. Most parents (91% boys' and
      80% girls') who participated in the process evaluation survey (n = 162) reported
      seeking additional information about the vaccine after receiving the postcard.
      Only 8% (57 of 1,062) of the adolescents assigned to a HIT provider with an
      office visit during the study used the HIT system. When compared with arms not
      containing that component, HPV vaccine initiation increased with the postcard
      campaign (girls, odds ratio [OR] = 1.6; 95% confidence interval [CI] = 1.1-2.3
      and boys, not significant), the HIT system (girls, OR = 1.5; 95% CI = 1.0-2.3 and
      boys, OR = 1.4; 95% CI = 1.0-2.0), and the combined HIT and postcard intervention
      (girls, OR = 2.4; 95% CI = 1.4-4.3 and boys, OR = 1.6; 95% CI = 1.0-2.5).
      CONCLUSIONS: A system-level postcard campaign was feasible. Despite low
      recruitment to the in-clinic HIT system, the intervention demonstrated short
      term, preliminary effectiveness similar to prior HPV vaccine interventions.

PMID- 25863555
TI  - Strategies for increasing adolescent immunizations in diverse ethnic communities.
AB  - PURPOSE: We sought to identify attitudes and knowledge of adolescent vaccination
      recommendations for tetanus, diphtheria, and acellular pertussis (Tdap);
      quadrivalent meningococcal conjugate (MCV4); and human papillomavirus (HPV)
      vaccines among Hispanic, Somali, and Ethiopian/Eritrean communities in King
      County, Washington. METHODS: In-person surveys of Hispanic, Somali, and
      Ethiopian/Eritrean adolescents (n = 45) and parents of adolescents (n = 157), and
      three focus groups with mothers of 11- to 18-year-olds were conducted to assess
      knowledge, attitudes, and barriers related to recommended adolescent vaccines.
      Bivariate analyses of parent survey responses were performed to evaluate possible
      differences between ethnic groups (chi-square test and Fisher exact test where
      possible). Findings were used to develop (1) culture-specific written brochures
      for community members, which addressed misperceptions about adolescent
      immunizations and related diseases, and (2) a presentation highlighting specific
      messages for health care providers (HCPs) in the target communities. HCPs were
      surveyed after delivery of the presentation (n = 20). RESULTS: We identified
      barriers to adolescent immunization including: parents' and adolescents' limited
      awareness of, and misperceptions regarding, recommended adolescent vaccines and
      vaccine preventable diseases; lack of HCP recommendations for vaccination; and
      inability to access health information in native languages. Awareness of tetanus,
      diphtheria, and acellular pertussis, quadrivalent meningococcal conjugate, and
      human papillomavirus vaccines varied by vaccine and ethnic group. Lack of
      knowledge of adolescent vaccination recommendations was the main reason given by
      parents that their adolescents had not been vaccinated. Most parents in the focus
      groups identified doctors as a trusted source of health information and reported
      that they would vaccinate their teens if their doctor recommended it. All the
      surveyed HCPs routinely recommend adolescent vaccines at well-child visits, 55%
      at acute visits, and 35% at injury visits. Eighty percent reported that they
      would be more likely to recommend HPV vaccine after our on-site presentation.
      CONCLUSIONS: A strong recommendation from the physician is a critical factor
      influencing parents' decision to vaccinate, even when hesitancy exists. Other
      factors (such as personal experiences with these diseases and religious and
      cultural beliefs) also influence parents' decisions regarding vaccination.
      Knowledge of beliefs, misperceptions, and concerns can help inform strategies to
      improve adolescent vaccine uptake among specific ethnic populations, including
      the availability of culturally tailored, translated information. Additionally,
      HCPs may benefit from guidance on communicating with ethnic populations to
      support meaningful dialogue with families about the risks and benefits of
      adolescent vaccines.

PMID- 25863556
TI  - Human papillomavirus vaccines: an ounce of prevention is worth pounds of cures.

PMID- 25863557
TI  - Understanding how different recruitment strategies impact parent engagement with
      an iPad-based intervention to provide personalized information about adolescent
      vaccines.
AB  - PURPOSE: Inadequate provider time for addressing parents' questions and concerns
      about adolescent vaccines is a barrier to vaccine utilization. We sought to
      determine how different recruitment strategies impact the degree of engagement
      with an intervention that provided this information via an iPad placed in a
      clinical setting. METHODS: We provided to three pediatric practices in the Denver
      area the "Teen VaxScene" web site that generates individually customized
      information for parents about adolescent vaccines. Three recruitment strategies
      were assessed for their impact on parental use of the intervention as follows:
      passive recruitment using posters to advertise a "kiosk" version of the
      intervention; posters plus a $10 incentive for using the kiosk; and posters plus
      a $10 incentive plus decoupling the iPad from the kiosks to enable "roving." We
      assessed the engagement with the intervention at multiple levels including log
      in, consent, and completion of a baseline survey and viewing individually
      tailored web pages. Surveys were used to assess barriers to using the
      intervention. RESULTS: During the 14-month study period, 693 people had contact
      with the iPad, 199 consented, and 48 completed the survey to enable creation of
      tailored content; and 42 used the tailored site. Five times as many parents (n =
      40) consented to participation during the 2 months when the intervention was
      "roving" than during the 10-month "passive" recruitment period. Engagement with
      the tailored material was low, with most users viewing only the "table of
      contents" pages. Utilizers and nonutilizers of the intervention had similar
      demographic characteristics. CONCLUSIONS: Enabling the iPad to "rove" in the
      clinic greatly increased the proportion of parents consenting to use the
      intervention. However, meaningful engagement with the material was low. Further
      research is needed to understand the most effective and time efficient ways to
      provide vaccine-related educational information to parents of adolescents.

PMID- 25863558
TI  - Late-life Depression Modifies the Association Between Cerebral White Matter
      Hyperintensities and Functional Decline Among Older Adults.
AB  - OBJECTIVE: Vascular lesions seen through brain imaging as hyperintensities are
      associated with both depression and functional impairment in older adults. Our
      objective was to determine if the relationship between the volume of cerebral
      white matter hyperintensities (WMHs) and functional decline differed in the
      presence of late life depression. DESIGN: Secondary analysis of data collected
      through the Neurocognitive Outcomes of Depression Study. Analysis techniques
      included general linear mixed models examining trajectories of functional change
      predicted by lesion volume at baseline. PARTICIPANTS: 381 participants (244
      patients diagnosed with major depression and 137 never depressed comparison
      participants) ages 60 years and older followed for up to 16 years. MEASUREMENTS:
      WMH volume was measured through analysis of brain magnetic resonance imaging
      data. Functional limitations included difficulties with basic activities of daily
      living tasks, instrumental activities of daily living tasks, and mobility.
      RESULTS: Those participants who were both depressed and had a higher volume of
      WMHs at baseline were most at risk for functional decline across all measures of
      function. Among the never depressed, those with a higher WMH volume at baseline
      had a more accelerated rate of functional decline than those with lower WMH
      volume, and those who were depressed with lower volume of WMH started with more
      limitations than the never depressed but appeared to progress at a rate similar
      to those who were never depressed with lower WMH. CONCLUSION: Older patients with
      both cerebrovascular risk factors and depression are at an increased risk for
      functional decline, and may benefit from the treatment of both conditions.

PMID- 25863560
TI  - Tuberculosis and vitamin D: what's the rest of the story?

PMID- 25863559
TI  - Ledipasvir and sofosbuvir fixed-dose combination with and without ribavirin for
      12 weeks in treatment-naive and previously treated Japanese patients with
      genotype 1 hepatitis C: an open-label, randomised, phase 3 trial.
AB  - BACKGROUND: Compared with other countries, patients with chronic hepatitis C
      infection in Japan tend to be older, have more advanced liver disease, and are
      more likely to have been previously treated for hepatitis C. We aimed to assess
      the efficacy and safety of an all-oral, fixed-dose combination of the hepatitis C
      virus NS5A inhibitor ledipasvir and the NS5B nucleotide polymerase inhibitor
      sofosbuvir with and without ribavirin for 12 weeks in treatment-naive and
      previously treated Japanese patients with chronic genotype 1 hepatitis C virus
      infection. METHODS: In this randomised, open-label study, we enrolled patients
      from 19 clinical Japanese centres. Patients were randomly assigned (1:1) to
      receive either ledipasvir (90 mg) and sofosbuvir (400 mg) or ledipasvir,
      sofosbuvir, and ribavirin (dosed according to the Japanese Copegus product label
      ie, patients <=60 kg received 600 mg daily, patients >60 kg to <=80 kg received
      800 mg daily, and patients >80 kg received 1000 mg daily) orally once daily for
      12 weeks. After completion or early discontinuation of treatment, patients were
      followed up off-treatment for 24 weeks. Eligible patients were at least 20 years
      of age with chronic genotype 1 hepatitis C virus infection with serum hepatitis C
      virus RNA concentrations of at least 5 log10 IU/mL, creatinine clearance of at
      least 1.0 mL/s, and a platelet count of at least 50 * 10(9) per L. An interactive
      web response system was used to manage patient randomisation and treatment
      assignment. Randomisation was stratified by the presence or absence of cirrhosis
      for treatment-naive patients and stratified by presence or absence of cirrhosis
      and by previous treatment category (relapser or breakthrough, non-responder, or
      interferon-intolerant) for previously treated patients. Within each strata,
      patients were sequentially assigned to either treatment with ledipasvir
      sofosbuvir or ledipasvir-sofosbuvir plus ribavirin in a 1:1 ratio with block size
      of 4. The primary endpoint was sustained virological response 12 weeks after
      completion of treatment (SVR12) assessed in all patients who were randomly
      assigned and received at least one dose of study drug; safety outcomes were
      assessed in all patients who received at least one dose of study drug. This trial
      is registered with ClinicalTrials.gov, number NCT01975675. FINDINGS: Between Oct
      15, 2013 and Dec 13, 2013, 341 patients were randomly assigned to treatment
      groups and received at least one dose of study treatment. SVR12 was achieved in
      all 171 (100%) patients (83 of 83 treatment naive and 88 of 88 treatment
      experienced) receiving ledipasvir-sofosbuvir (95% CI 98-100) and 167 (98%) of 170
      patients (80 of 83 treatment naive and 87 of 87 treatment experienced) receiving
      ledipasvir-sofosbuvir plus ribavirin (95% CI 95-100). Of the 76 patients with
      baseline NS5A resistant variants, 75 (99%) achieved SVR12. Two (1.2%) of 170
      patients in the ledipasvir-sofosbuvir plus ribavirin group discontinued treatment
      because of adverse events. The most common adverse events were nasopharyngitis
      (50 [29.2%] of 171), headache (12 [7.0%] of 171), and malaise (nine [5.3%] of
      171) in patients receiving ledipasvir-sofosbuvir; and nasopharyngitis (40 [23.5%]
      of 170), anaemia (23 [13.5%] of 170), and headache in those receiving ledipasvir
      sofosbuvir and ribavirin (15 [8.8%] of 170). INTERPRETATION: Although existing
      regimens for the treatment of hepatitis C virus are effective for many patients,
      medical needs remain unmet, particularly in Japan where the population with
      hepatitis C virus genotype 1 is generally older and treatment-experienced, with
      advanced liver disease. The efficacy, tolerability, and absence of drug-drug
      interactions of ledipasvir-sofosbuvir suggest that it could be an important
      option for treatment of genotype 1 hepatitis C virus in Japanese patients.
      FUNDING: Gilead Sciences.

PMID- 25863561
TI  - A pill a day keeps HCV away.

PMID- 25863562
TI  - Adjunctive vitamin D for treatment of active tuberculosis in India: a randomised,
      double-blind, placebo-controlled trial.
AB  - BACKGROUND: Vitamin D has immunomodulatory effects that might aid clearance of
      mycobacterial infection. We aimed to assess whether vitamin D supplementation
      would reduce time to sputum culture conversion in patients with active
      tuberculosis. METHODS: We did this randomised, double-blind, placebo-controlled,
      superiority trial at 13 sites in India. Treatment-naive patients who were sputum
      smear positive, HIV negative, and had pulmonary tuberculosis were randomly
      assigned (1:1), with centrally labelled, serially numbered bottles, to receive
      standard active tuberculosis treatment with either supplemental high-dose oral
      vitamin D3 (four doses of 2.5 mg at weeks 0, 2, 4, and 6) or placebo. Neither the
      patients nor the clinical and laboratory investigators and personnel were aware
      of treatment assignment. The primary efficacy outcome was time to sputum culture
      conversion. Analysis was by modified intention to treat. This trial is registered
      with ClinicalTrials.gov, number NCT00366470. FINDINGS: Between Jan 20, 2010, and
      Aug 23, 2011, we randomly assigned 247 participants to the vitamin D group
      (n=121) or the placebo group (n=126), of whom 211 participants (n=101 and n=110,
      respectively) were included in the primary efficacy analysis. Median time to
      culture conversion in the vitamin D group was 43.0 days (95% CI 33.3-52.8) versus
      42.0 days (33.9-50.1) in the placebo group (log-rank p=0.95). Three (2%) patients
      died in the vitamin D group and one (1%) patient died in the placebo group; no
      death was considered attributable to the study intervention. No patients had
      hypercalcaemia. INTERPRETATION: Our findings show that vitamin D supplementation
      did not reduce time to sputum culture conversion. Further studies should
      investigate the role of vitamin D in prevention or reactivation of tuberculosis
      infection. FUNDING: Dalhousie University and Infectious Diseases Training and
      Research Centre.

PMID- 25863563
TI  - A more detailed picture of the epidemiology of Middle East respiratory syndrome
      coronavirus.

PMID- 25863564
TI  - Presence of Middle East respiratory syndrome coronavirus antibodies in Saudi
      Arabia: a nationwide, cross-sectional, serological study.
AB  - BACKGROUND: Scientific evidence suggests that dromedary camels are the
      intermediary host for the Middle East respiratory syndrome coronavirus (MERS
      CoV). However, the actual number of infections in people who have had contact
      with camels is unknown and most index patients cannot recall any such contact. We
      aimed to do a nationwide serosurvey in Saudi Arabia to establish the prevalence
      of MERS-CoV antibodies, both in the general population and in populations of
      individuals who have maximum exposure to camels. METHODS: In the cross-sectional
      serosurvey, we tested human serum samples obtained from healthy individuals older
      than 15 years who attended primary health-care centres or participated in a
      national burden-of-disease study in all 13 provinces of Saudi Arabia.
      Additionally, we tested serum samples from shepherds and abattoir workers with
      occupational exposure to camels. Samples were screened by recombinant ELISA and
      MERS-CoV seropositivity was confirmed by recombinant immunofluorescence and
      plaque reduction neutralisation tests. We used two-tailed Mann Whitney U exact
      tests, chi(2), and Fisher's exact tests to analyse the data. FINDINGS: Between
      Dec 1, 2012, and Dec 1, 2013, we obtained individual serum samples from 10,009
      individuals. Anti-MERS-CoV antibodies were confirmed in 15 (0.15%; 95% CI 0.09
      0.24) of 10,009 people in six of the 13 provinces. The mean age of seropositive
      individuals was significantly younger than that of patients with reported,
      laboratory-confirmed, primary Middle Eastern respiratory syndrome (43.5 years [SD
      17.3] vs 53.8 years [17.5]; p=0.008). Men had a higher antibody prevalence than
      did women (11 [0.25%] of 4341 vs two [0.05%] of 4378; p=0.028) and antibody
      prevalence was significantly higher in central versus coastal provinces (14
      [0.26%] of 5479 vs one [0.02%] of 4529; p=0.003). Compared with the general
      population, seroprevalence of MERS-CoV antibodies was significantly increased by
      15 times in shepherds (two [2.3%] of 87, p=0.0004) and by 23 times in
      slaughterhouse workers (five [3.6%] of 140; p<0.0001). INTERPRETATION:
      Seroprevalence of MERS-CoV antibodies was significantly higher in camel-exposed
      individuals than in the general population. By simple multiplication, a projected
      44,951 (95% CI 26,971-71,922) individuals older than 15 years might be
      seropositive for MERS-CoV in Saudi Arabia. These individuals might be the source
      of infection for patients with confirmed MERS who had no previous exposure to
      camels. FUNDING: European Union, German Centre for Infection Research, Federal
      Ministry of Education and Research, German Research Council, and Ministry of
      Health of Saudi Arabia.

PMID- 25863566
TI  - Scleral contact lenses and hypoxia: Theory versus practice.

PMID- 25863565
TI  - Can c-myc amplification reliably discriminate postradiation from primary
      angiosarcoma of the breast?
AB  - PURPOSE: Breast angiosarcomas are rare vascular malignancies that arise secondary
      to irradiation or de novo as primary tumours. The aim of this study is to know
      whether c-myc amplification can reliably discriminate these two entities.
      MATERIEL AND METHODS: Forty-seven patients treated for breast angiosarcomas were
      studied. Thirty-two patients were diagnosed with postradiation angiosarcomas
      after breast cancer treatment and 15 patients with primary angiosarcomas.
      Interphase fluorescence in situ hybridization (FISH) was performed by
      hybridization of probes covering C-MYC (chromosome 8q24.21) and CEP8 on tissue
      sections. RESULTS: Amplification (5- to 20-fold) of the c-myc oncogene was found
      in all breast radiation-induced angiosarcomas (32 tumours) but in none of the 15
      primary angiosarcomas except one (7%). CONCLUSION: This study reinforces that
      there are true pathogenetic differences between the two types of breast
      angiosarcomas which are morphologically indistinguishable. These data point the
      pathways preferentially involved in the pathogenesis of post radiation
      angiosarcomas of the breast and may provide the basis for an additional targeted
      therapy.

PMID- 25863567
TI  - Intralabyrinthine schwannomas.
AB  - This article reviews the relevant anatomy, pathophysiology, clinical
      presentation, radiographic differential, management, outcomes, and rehabilitation
      of patients with intralabyrinthine schwannomas. 

PMID- 25863568
TI  - Chordoma and chondrosarcoma.
AB  - Chordoma and chondrosarcoma represent 2 fundamentally different and challenging
      central skull base pathologies. Both are largely surgical diseases with varying
      outcomes based on completeness of resection. Adjuvant therapy is controversial,
      although radiation therapy is commonly employed postoperatively, and stereotactic
      radiosurgery is used either in primary management or treatment of local
      progression. 

PMID- 25863569
TI  - Historical perspective on evolution in management of lateral skull base tumors.
AB  - This article gives a history of the major advances that have contributed to the
      current management of lateral skull base lesions. These advances include changes
      in surgical technique, better understanding of the natural history of these
      lesions, and the advent of stereotactic radiosurgery. An understanding of how
      treatment has evolved over time improves understanding of how the current
      treatment methods have been developed. 

PMID- 25863570
TI  - Petroclival meningiomas.
AB  - Petroclival meningiomas are most commonly found in women around 50 years of age
      and have the general tendency to grow and affect several cranial nerves. At
      presentation, many patients complain of headaches, gait disturbances and cranial
      neuropathies. Treatment options include surgery, with a variety of surgical
      approaches, and or radiotherapy. Current trends support subtotal resection with
      postoperative radiotherapy. This review summarizes the literature of petroclival
      meningiomas, discussing topics including definitions, genetics, common presenting
      signs and symptoms, imaging characteristics, natural history, common surgical
      approaches, surgical outcomes, complications, and radiotherapy. 

PMID- 25863571
TI  - Lights and shadows in the challenge of binding acyclovir, a synthetic purine-like
      nucleoside with antiviral activity, at an apical-distal coordination site in
      copper(II)-polyamine chelates.
AB  - Several nucleic acid components and their metal complexes are known to be
      involved in crucial metabolic steps. Therefore the study of metal-nucleic acid
      interactions becomes essential to understand these biological processes. In this
      work, the synthetic purine-like nucleoside acyclovir (acv) has been used as a
      model of guanosine recognition with copper(II)-polyamine chelates. The chemical
      stability of the N9-acyclic arm in acv offers the possibility to use this
      antiviral drug to deepen the knowledge of metal-nucleoside interactions. Cu(II)
      chelates with cyclam, cyclen and trien were used as suitable receptors. All these
      copper(II) tetraamine chelates have in common the potential ability to yield a Cu
      N7(apical) bond assisted by an appropriate (amine)N-H?O6(acv) intra-molecular
      interligand interaction. A series of synthesis afforded the following compounds:
      [Cu(cyclam)(ClO4)2] (1), {[Cu(cyclam)(MU2-NO3)](NO3)}n (2), {[Cu(cyclam)(MU2
      SO4)].MeOH}n (3), {[Cu(cyclam)(MU2-SO4)].5H2O}n (4), [Cu(cyclen)(H2O)]SO4.2H2O
      (5), [Cu(cyclen)(H2O)]SO4.3H2O (6), [Cu(trien)(acv)](NO3)2.acv (7) and
      [Cu(trien)(acv)]SO4.0.71H2O (8). All these compounds have been characterized by X
      ray crystallography and FT-IR spectroscopy. Our results reveal that the
      macrochelates Cu(cyclen)(2+) and Cu(cyclam)(2+) are unable to bind acv at an
      apical site. In contrast, the Cu(trien)(2+) complex has proved to be an efficient
      receptor for acv in compounds (7) and (8). In the ternary complex
      [Cu(trien)(acv)](2+), the metal binding pattern of acv consists of an apical Cu
      N7 bond assisted by an intra-molecular (primary amino)N-H?O6(acv) interligand
      interaction. Structural comparisons reveal that this unprecedented apical role of
      acv is due to the acyclic nature of trien together with the ability of the
      Cu(trien)(2+) chelate to generate five-coordinated (type 4+1) copper(II)
      complexes. 

PMID- 25863572
TI  - Design of renal denervation studies not confounded by antihypertensive drugs.

PMID- 25863573
TI  - Grim status of hypertension in rural China: results from Northeast China Rural
      Cardiovascular Health Study 2013.
AB  - The last study that reported the prevalence of hypertension in rural Northeast
      China was conducted approximately 10 years ago. We aimed to update the data on
      the prevalence and epidemiologic features of hypertension in rural Northeast
      China. This study examined a total of 11,576 adults using a multi-stage cluster
      sampling method to select a representative sample of individuals 35 years or
      older. Sitting blood pressure was measured three times for each participant by
      trained observers using a standardized electric sphygmomanometer after resting
      for 5 minutes. Related medical histories were obtained using a standard
      questionnaire, and blood biochemical indexes were collected by well-trained
      personnel. Prevalence of hypertension was 51.1%; 53.9% for men and 48.7% for
      women. Among subjects with hypertension, 43.5% were aware of the diagnosis, and
      31.2% were taking antihypertensive medications, but only 6% had their blood
      pressure controlled. Besides traditional risk factors, multiple logistic
      regression analysis indicated that obesity, diabetes, dyslipidemia, and
      hyperuricemia were becoming risk factors for hypertension in this rural area.The
      status of hypertension is grim currently in rural Northeast China. The prevalence
      of hypertension remains seriously high, while the control rate is still
      frustratingly low. Obesity, diabetes, dyslipidemia, and hyperuricemia were more
      likely to be associated with hypertension in this rural area.

PMID- 25863574
TI  - Residual impact of aged nZVI on heavy metal-polluted soils.
AB  - In the present study, the residual toxicity and impact of aged nZVI after a
      leaching experiment on heavy metal (Pb, Zn) polluted soils was evaluated. No
      negative effects on physico-chemical soil properties were observed after aged
      nZVI exposure. The application of nZVI to soil produced a significant increase in
      Fe availability. The impact on soil biodiversity was assessed by fluorescence in
      situ hybridization (FISH). A significant effect of nZVI application on microbial
      structure has been recorded in the Pb-polluted soil nZVI-treated. Soil bacteria
      molecular response, evaluated by RT-qPCR using exposure biomarkers (pykA, katB)
      showed a decrease in the cellular activity (pykA) due to enhanced intracellular
      oxidative stress (katB). Moreover, ecotoxicological standardised test on
      Caenorhabditis elegans (C. elegans) showed a decrease in the growth endpoint in
      the Pb-polluted soil, and particularly in the nZVI-treated. A different pattern
      has been observed in Zn-polluted soils: no changes in soil biodiversity, an
      increase in biological activity and a significant decrease of Zn toxicity on C.
      elegans growth were observed after aged nZVI exposure. The results reported
      indicated that the pollutant and its nZVI interaction should be considered to
      design soil nanoremediation strategies to immobilise heavy metals. 

PMID- 25863575
TI  - Detection of Pseudomonas aeruginosa by a triplex polymerase chain reaction assay
      based on lasI/R and gyrB genes.
AB  - Pseudomonas aeruginosa is a nosocomial pathogen, which, due to its inherent and
      acquired resistance to a wide range of antibiotics, causes high mortality rates.
      Therefore, rapid detection of the bacterium with high specificity and sensitivity
      plays a critical role in the control of the pathogenic bacterium. The aim of this
      study was to evaluate the accuracy and specificity of a prompt detection of the
      bacterium based on a triplex polymerase chain reaction that amplifies the lasI,
      lasR and gyrB genes. For this purpose, 30 clinical isolates of P. aeruginosa and
      30 wound biopsy samples were retrieved from clinical diagnostic laboratories.
      After the extraction of the chromosomal DNA, the desired genes were amplified
      using uniplex and triplex PCR with appropriate primers. The specificity of the
      primers was evaluated by a comparison of the PCR results for P. aeruginosa
      clinical samples and non-Pseudomonas species control samples. The sensitivity of
      the primers was determined using a serial dilution of the genomic DNA template
      (100 ng to 100 fg) and by a comparison of the PCR and bacterial culture results.
      The results showed that the triplex PCR assay was positive for all of the samples
      (100%), while the PCR identifications were negative for non-Pseudomonas species.
      Additionally, at 10(-4) and 10(-5) diluted genomic DNA from P. aeruginosa (10 pg
      and 1 pg), the triplex PCR test was positive for the Las and gyrB genes in all of
      the samples, respectively. Based on these results, the designed primers can be
      used for the rapid, specific and sensitive diagnosis of P. aeruginosa in a
      triplex PCR assay.

PMID- 25863576
TI  - Implanted-ion betaNMR: A new probe for nanoscience.
AB  - NMR detected by radioactive beta decay, beta-NMR, is undergoing a renaissance
      largely due to the availability of high intensity low energy beams of the most
      common probe ion, Li+8, and dedicated facilities for materials research. The
      radioactive detection scheme, combined with the low energy ion beam, enable depth
      resolved NMR measurements in crystals, thin films and multilayers on depth scales
      of 2-200 nm. After a brief historical introduction, technical aspects of
      implanted-ion beta-NMR are presented, followed by a review of recent applications
      to a wide range of solids.

PMID- 25863577
TI  - [Closed claims in obstetrics: A study based on French Sham insurance data].
AB  - OBJECTIVE: The aim of this study was to analyze the medicolegal claims related to
      obstetrics in French hospitals. MATERIAL AND METHODS: We did retrospective study
      on insurance claims provided by Sham insurances and which has been settled by a
      court over a 3-year period (2004-2006). RESULTS: We analyzed 66 closed claims
      that occurred between 1983 and 2005 in French hospitals (54 general hospitals and
      12 academic). The average time between the declaration of the claim and the court
      conviction was 6 years. The average amount of compensation per claim was 500,000
      ?. The damage occurred during vaginal delivery (n=44), planned (n=5) or unplanned
      (n=4) cesarean. The more often claims are fetal asphyxia (n=24) or shoulder
      dystocia (n=8). The consequences are very important: cerebral palsy (16), death
      of the newborn (12), death of the mother (2) or brachial plexus injuries (6).
      CONCLUSION: The causes identified by the expert are always multifactorial with
      generally a misdiagnosis (n=27), a decision making error (n=36), a care error by
      the midwife (n=21) and/or a delay in medical care (n=13). These data should help
      strengthen the quality approach in obstetrics.

PMID- 25863578
TI  - Influence of powdered activated carbon addition on water quality, sludge
      properties, and microbial characteristics in the biological treatment of
      commingled industrial wastewater.
AB  - A powdered activated carbon-activated sludge (PAC-AS) system, a traditional
      activated sludge (AS) system, and a powdered activated carbon (PAC) system were
      operated to examine the insights into the influence of PAC addition on biological
      treatment. The average COD removal efficiencies of the PAC-AS system (39%) were
      nearly double that of the AS system (20%). Compared with the average efficiencies
      of the PAC system (7%), COD removal by biodegradation in the PAC-AS system was
      remarkably higher than that in the AS system. The analysis of the influence of
      PAC on water quality and sludge properties showed that PAC facilitated the
      removal of hydrophobic matter and metabolic acidic products, and also enhanced
      the biomass accumulation, sludge settleability, and specific oxygen uptake rate
      inside the biological system. The microbial community structures in the PAC-AS
      and AS systems were monitored. The results showed that the average well color
      development in the PAC-AS system was higher than that in the AS system. The
      utilization of various substrates by microorganisms in the two systems did not
      differ. The dissimilarity index was far less than one; thus, showing that the
      microbial community structures of the two systems were the same. 

PMID- 25863579
TI  - Monitoring tryptophan metabolism after exposure to hexaconazole and the
      enantioselective metabolism of hexaconazole in rat hepatocytes in vitro.
AB  - In the present study, the enantioselective metabolism, cytotoxicity of
      hexaconazole and its influence on tryptophan metabolism in rat hepatocytes in
      vitro were investigated. Following the exposure of primary rat hepatocytes to rac
      hexaconazole, the concentrations of its enantiomers in the media were determined
      by chiral high-performance liquid chromatography-tandem mass spectrometry (HPLC
      MS/MS). The half-lives (t1/2) of (+)-hexaconazole and (-)-hexaconazole were 5.17
      h and 19.80 h, respectively, indicating that the metabolic process was
      enantioselective with (-)-hexaconazole enrichment. Using the MTT method, the EC50
      values of rac-hexaconazole, (+)-hexaconazole and (-)-hexaconazole after 12h of
      exposure were determined to be 71.62, 62.71 and 67.94 MUM, respectively.
      Tryptophan metabolism was monitored using metabolomics profiling techniques.
      Hexaconazole and its enantiomers caused the down-regulation of tryptophan levels
      and the up-regulation of kynurenine (KYN) levels, suggesting a role for
      hexaconazole in the activation of the KYN pathway and providing information for
      the mechanism of its toxicity.

PMID- 25863580
TI  - Dialkylmethyl-2-(N,N-diisobutyl)acetamidoammonium iodide as a ruthenium selective
      ligand from nitric acid medium.
AB  - A new class of quaternary ammonium iodide based ligands with 2-(N,N
      diisobutyl)acetamide as an alkyl appendage have been designed, synthesized and
      tested for their ability to extract ruthenium selectively from nitric acid
      medium. The 2-(N,N-diisobutyl)acetamido ammonium iodide with two propyl and a
      methyl substituents showed best results for the recovery of ruthenium. The
      optimized concentration of the solvent was found to be 0.2M in 30% isodecyl
      alcohol/n-dodecane. The stoichiometry of the complex was ascertained by slope
      analysis method and was found to be 1:1 with respect to ligand L(+)I(-) and
      Ru(NO)(NO3)3. Ruthenium formed an adduct of structure LRu(NO)(NO3)3 I in the
      extraction medium. Iodide ion played an important role in the formation of the
      stable and extractable complex of ruthenium. No extraction was observed when
      iodide was replaced by nitrate anion in the ligand. The ligand also showed good
      selectivity for ruthenium in the presence of other metal ions commonly found in
      nitric acid solutions of nuclear waste.

PMID- 25863581
TI  - Measurement invariance of alcohol instruments with Hispanic youth.
AB  - INTRODUCTION: Despite their widespread use across clinical and research settings,
      no study has yet investigated the fit of several standard alcohol measures for
      Hispanic youth, including those used to assess motivation to change, self
      efficacy, peer norms, and problem drinking. This study thus served to address
      this gap by evaluating measurement invariance with substance-using youth.
      METHODS: We enrolled a large sample of regular substance-using youth who were
      involved with the justice system (N=368; 72.9% male; 76.9% Hispanic; M
      age=16.17years). Similar to the broader Hispanic population of the southwest
      United States (U.S.), Hispanic youth in the sample were on average 3.5th
      generation (with at least 1 foreign-born grand-parent). Following standard
      administration and scoring procedures, all youth completed measures of motivation
      to change (e.g., readiness rulers, intentions to change), self-efficacy (e.g.,
      drink refusal in social situations), peer norms (e.g., peer norms for substance
      use), and problem drinking (e.g., substance use quantity/frequency; Alcohol Use
      Disorders Identification Test; Rutgers Alcohol Problems Index; Timeline
      FollowBack). Measurement equivalence was evaluated via multiple group
      confirmatory factor analysis. RESULTS: Our results indicated that each measure
      evaluated herein worked equally well for Hispanic and Caucasian youth. We found
      measurement invariance at every level tested. CONCLUSIONS: This study supports
      the validity and future use of these important and widely-used alcohol use
      measures for high-risk substance-using Hispanic youth. Further, given the
      representativeness of this sample within the southwestern U.S., these results
      show promise for generalizability to U.S.-born Hispanic youth within this
      geographic region.

PMID- 25863582
TI  - Meta-analyses of randomized controlled trials show suboptimal validity of
      surrogate outcomes for overall survival in advanced colorectal cancer.
AB  - OBJECTIVES: To quantify and compare the treatment effects on three surrogate end
      points, progression-free survival (PFS), time to progression (TTP), and tumor
      response rate (TR) vs. overall survival (OS) based on a meta-analysis of
      randomized controlled trials (RCTs) of drug interventions in advanced colorectal
      cancer (aCRC). STUDY DESIGN AND SETTING: We systematically searched for RCTs of
      pharmacologic therapies in aCRC between 2003 and 2013. Trial characteristics,
      risk of bias, and outcomes were recorded based on a predefined form. Univariate
      and multivariate random-effects meta-analyses were used to estimate pooled
      summary treatment effects. The ratio of hazard ratios (HRs)/odds ratios (ORs) and
      difference in medians were used to quantify the degree of difference in treatment
      effects on the surrogate end points and OS. Spearman rho, surrogate threshold
      effect (STE), and R(2) were also estimated across predefined trial-level
      covariates. RESULTS: We included 101 RCTs. In univariate and multivariate meta
      analyses, we found larger treatment effects for the surrogates than for OS.
      Compared with OS, treatment effects were on average 13% higher when HRs were
      measured and 3% to 45% higher when ORs were considered; differences in median
      PFS/TTP were higher than on OS by an average of 0.5 month. Spearman rho ranged
      from 0.39 to 0.80, mean R(2) from 0.06 to 0.65, and STE was 0.8 for HRPFS, 0.64
      for HRTTP, or 0.28 for ORTR. The stratified analyses revealed high variability
      across all strata. CONCLUSION: None of the end points in this study were found to
      achieve the level of evidence (ie, mean R(2)trial > 0.60) that has been set to
      select high or excellent correlation levels by common surrogate evaluation tools.
      Previous surrogacy relationships observed between PFS and TTP vs. OS in selected
      settings may not apply across other classes or lines of therapy.

PMID- 25863584
TI  - Convergent evolution and mimicry of protein linear motifs in host-pathogen
      interactions.
AB  - Pathogen linear motif mimics are highly evolvable elements that facilitate
      rewiring of host protein interaction networks. Host linear motifs and pathogen
      mimics differ in sequence, leading to thermodynamic and structural differences in
      the resulting protein-protein interactions. Moreover, the functional output of a
      mimic depends on the motif and domain repertoire of the pathogen protein.
      Regulatory evolution mediated by linear motifs can be understood by measuring
      evolutionary rates, quantifying positive and negative selection and performing
      phylogenetic reconstructions of linear motif natural history. Convergent
      evolution of linear motif mimics is widespread among unrelated proteins from
      viral, prokaryotic and eukaryotic pathogens and can also take place within
      individual protein phylogenies. Statistics, biochemistry and laboratory models of
      infection link pathogen linear motifs to phenotypic traits such as tropism,
      virulence and oncogenicity. In vitro evolution experiments and analysis of
      natural sequences suggest that changes in linear motif composition underlie
      pathogen adaptation to a changing environment. 

PMID- 25863583
TI  - Emerging targets in osteoarthritis therapy.
AB  - Osteoarthritis (OA) is a destructive joint disease in which the initiation may be
      attributed to direct injury and mechanical disruption of joint tissues, but the
      progressive changes are dependent on active cell-mediated processes that can be
      observed or inferred during the generally long time-course of the disease. Based
      on clinical observations and experimental studies, it is now recognized a that it
      is possible for individual patients to exhibit common sets of symptoms and
      structural abnormalities due to distinct pathophysiological pathways that act
      independently or in combination. Recent research that has focused on the
      underlying mechanisms involving biochemical cross talk among the cartilage,
      synovium, bone, and other joint tissues within a background of poorly
      characterized genetic factors will be addressed in this review. 

PMID- 25863586
TI  - Alignment of Children's Food Advertising With Proposed Federal Guidelines.
AB  - INTRODUCTION: It is well established that children are exposed to food marketing
      promoting calorically dense, low-nutrient products. Reducing exposure to
      obesogenic marketing presents an opportunity to improve children's health. The
      purpose of this study was to determine the extent to which televised food
      advertising practices targeting children (aged <=12 years) were consistent with
      guidelines proposed by a coalition of federal authorities known as the
      Interagency Working Group on Foods Marketed to Children (IWG). METHODS: A sample
      of children's TV programming aired on five national broadcast networks and two
      cable channels (N=103 shows) was recorded February to April 2013. The sample
      contained 354 food ads. Advertised products were identified and categorized using
      industry classification codes and nutrient data obtained from manufacturers.
      Product compliance with IWG saturated fat, trans fat, added sugar, and sodium
      guidelines was evaluated. RESULTS: Analyses conducted in 2013 revealed that
      nearly all food ads (94%) met guidelines for trans fats; 68% and 62% met
      guidelines for sodium and saturated fat, respectively; and 20% complied with
      added sugar guidelines. Overall, 1.4% of all child-targeted food ads met all
      aspects of IWG guidelines. CONCLUSIONS: Nearly all food advertisements exceeded
      guidelines for at least one recommended nutrient to limit. Individually,
      conformity was high for guidelines for trans fats, moderate for sodium and
      saturated fats, and poor for added sugar. These findings suggest that child
      targeted food advertising remains strongly biased toward less healthy options.
      Policymakers wishing to regulate food marketing should understand the amount and
      types of advertisements that children view.

PMID- 25863585
TI  - Relating sequence encoded information to form and function of intrinsically
      disordered proteins.
AB  - Intrinsically disordered proteins (IDPs) showcase the importance of
      conformational plasticity and heterogeneity in protein function. We summarize
      recent advances that connect information encoded in IDP sequences to their
      conformational properties and functions. We focus on insights obtained through a
      combination of atomistic simulations and biophysical measurements that are
      synthesized into a coherent framework using polymer physics theories. 

PMID- 25863587
TI  - The Surgeon General Should Say That Indoor Ultraviolet Radiation Tanning Causes
      Skin Cancer.

PMID- 25863588
TI  - Cyclohexane-1,2-dicarboxylic acid diisononyl ester and metabolite effects on rat
      epididymal stromal vascular fraction differentiation of adipose tissue.
AB  - Plastics are generally mixed with additives like plasticizers to enhance their
      flexibility, pliability, and elasticity proprieties. Plasticizers are easily
      released into the environment and are absorbed mainly through ingestion, dermal
      contact, and inhalation. One of the main classes of plasticizers, phthalates, has
      been associated with endocrine and reproductive diseases. In 2002, 1,2
      cyclohexane dicarboxylic acid diisononyl ester (DINCH) was introduced in the
      market for use in plastic materials and articles intended to come into contact
      with food, and it received final approval from the European Food Safety Authority
      in 2006. At present, there is limited knowledge about the safety and potential
      metabolic and endocrine-disrupting properties of DINCH and its metabolites. The
      purpose of this study was to evaluate the biological effects of DINCH and its
      active metabolites, cyclohexane-1,2-dicarboxylic acid (CHDA) and cyclohexane-1,2
      dicarboxylic acid mono isononyl ester (MINCH), on rat primary stromal vascular
      fraction (SVF) of adipose tissue. DINCH and its metabolite, CHDA, were not able
      to directly affect SVF differentiation. However, exposure of SVF to 50 MUM and
      100 MUM concentrations of MINCH affected the expression of Cebpa and Fabp4, thus
      inducing SVF preadipocytes to accumulate lipids and fully differentiate into
      mature adipocytes. The effect of MINCH was blocked by the specific peroxisome
      proliferator-activated receptor (PPAR)-alpha antagonist, GW6471. Taken together,
      these results suggest that MINCH is a potent PPAR-alpha agonist and a metabolic
      disruptor, capable of inducing SVF preadipocyte differentiation, that may
      interfere with the endocrine system in mammals.

PMID- 25863589
TI  - Applicability of western chemical dietary exposure models to the Chinese
      population.
AB  - A range of exposure models, which have been developed in Europe and North
      America, are playing an increasingly important role in priority setting and the
      risk assessment of chemicals. However, the applicability of these tools, which
      are based on Western dietary exposure pathways, to estimate chemical exposure to
      the Chinese population to support the development of a risk-based environment and
      exposure assessment, is unclear. Three frequently used modelling tools, EUSES,
      RAIDAR and ACC-HUMANsteady, have been evaluated in terms of human dietary
      exposure estimation by application to a range of chemicals with different
      physicochemical properties under both model default and Chinese dietary
      scenarios. Hence, the modelling approaches were assessed by considering dietary
      pattern differences only. The predicted dietary exposure pathways were compared
      under both scenarios using a range of hypothetical and current emerging
      contaminants. Although the differences across models are greater than those
      between dietary scenarios, model predictions indicated that dietary preference
      can have a significant impact on human exposure, with the relatively high
      consumption of vegetables and cereals resulting in higher exposure via plants
      based foodstuffs under Chinese consumption patterns compared to Western diets.
      The selected models demonstrated a good ability to identify key dietary exposure
      pathways which can be used for screening purposes and an evaluative risk
      assessment. However, some model adaptations will be required to cover a number of
      important Chinese exposure pathways, such as freshwater farmed-fish, grains and
      pork. 

PMID- 25863590
TI  - Variation in vulnerability to extreme-temperature-related mortality in Japan: A
      40-year time-series analysis.
AB  - BACKGROUND: Although the impact of extreme heat and cold on mortality has been
      documented in recent years, few studies have investigated whether variation in
      susceptibility to extreme temperatures has changed in Japan. METHODS: We used
      data on daily total mortality and mean temperatures in Fukuoka, Japan, for 1973
      2012. We used time-series analysis to assess the effects of extreme hot and low
      temperatures on all-cause mortality, stratified by decade, gender, and age,
      adjusting for time trends. We used a multivariate meta-analysis with a
      distributed lag non-linear model to estimate pooled non-linear lag-response
      relationships associated with extreme temperatures on mortality. RESULTS: The
      relative risk of mortality increased during heat extremes in all decades, with a
      declining trend over time. The mortality risk was higher during cold extremes for
      the entire study period, with a dispersed pattern across decades. Meta-analysis
      showed that both heat and cold extremes increased the risk of mortality. Cold
      effects were delayed and lasted for several days, whereas heat effects appeared
      quickly and did not last long. CONCLUSIONS: Our study provides quantitative
      evidence that extreme heat and low temperatures were significantly and non
      linearly associated with the increased risk of mortality with substantial
      variation. Our results suggest that timely preventative measures are important
      for extreme high temperatures, whereas several days' protection should be
      provided for extreme low temperatures.

PMID- 25863591
TI  - Effects of airborne particulate matter on alternative pre-mRNA splicing in colon
      cancer cells.
AB  - Alternative pre-mRNA splicing plays key roles in determining tissue- and species
      specific cell differentiation as well as in the onset of hereditary disease and
      cancer, being controlled by multiple post- and co-transcriptional regulatory
      mechanisms. We report here that airborne particulate matter, resulting from
      industrial pollution, inhibits expression and specifically affects alternative
      splicing at the 5' untranslated region of the mRNA encoding the bone
      morphogenetic protein BMP4 in human colon cells in culture. These effects are
      consistent with a previously reported role for BMP4 in preventing colon cancer
      development, suggesting that ingestion of particulate matter could contribute to
      the onset of colon cell proliferation. We also show that the underlying mechanism
      might involve changes in transcriptional elongation. This is the first study to
      demonstrate that particulate matter causes non-pleiotropic changes in alternative
      splicing. 

PMID- 25863592
TI  - Mercury in fish of the Madeira river (temporal and spatial assessment), Brazilian
      Amazon.
AB  - The Madeira River is the largest tributary of the Amazon River Basin and one of
      the most impacted by artisanal gold-mining activities, deforestation for
      agricultural projects, and recent hydroelectric reservoirs. Total Hg (and
      methylmercury-MeHg) concentrations was determined in 3182 fish samples of 84
      species from different trophic levels as a function of standard size. Species at
      the top of the trophic level (Piscivorous, Carnivorous) showed the highest mean
      total Hg concentrations (51-1242 ug/kg), Planctivorous and Omnivorous species
      showed intermediate total Hg concentrations (26-494 ug/kg), while Detritivorous
      and Herbivorous species showed the lowest range of mean total Hg concentrations
      (9-275 ug/kg). Significant correlations between fish size (standard length) and
      total Hg concentrations were seen for Planctivorous (r=0.474, p=0.0001),
      Piscivorous (r=0.459, p=0.0001), Detritivorous (r=0.227, p=0.0001), Carnivorous
      (r=0.212, p=0.0001), and Herbivorous (r=0.156, p=0.01), but not for the
      Omnivorous species (r=-0.064, p=0.0685). Moreover, fish trophic levels influenced
      the ratio of MeHg to total Hg (ranged from 70% to 92%). When adjusted for
      standard body length, significant increases in Hg concentrations in the last 10
      years were species specific. Spatial differences, albeit significant for some
      species, were not consistent with time trends for environmental contamination
      from past alluvial gold mining activities. Fish-Hg bioaccumulation is species
      specific but fish feeding strategies are the predominant influence in the fish-Hg
      bioaccumulation pattern.

PMID- 25863593
TI  - Human inorganic mercury exposure, renal effects and possible pathways in Wanshan
      mercury mining area, China.
AB  - Rice can accumulate methylmercury (MeHg) and rice consumption is the main route
      of MeHg exposure for the local population in Guizhou, China. However, inorganic
      Hg (IHg) load in human body is not comprehensively studied in highly Hg polluted
      areas such as Hg mining areas. This study is designed to evaluate human IHg
      exposure, related renal effects and possible pathways in Wanshan Hg mining area,
      Guizhou, Southwest China. Residents lived within 3 km to the mine waste heaps
      showed high Urine Hg (UHg) concentrations and the geometrical means (Geomean) of
      UHg were 8.29, 5.13, and 10.3 MUg/g Creatinine (Cr) at site A, D, and E,
      respectively. It demonstrated a gradient of UHg concentrations with the distance
      from the pollution sources. A significantly positive correlation between paired
      results for UHg concentrations and serum creatinine (SCr) was observed in this
      study, but not for UHg and blood urea nitrogen (BUN). There are significant
      increases of SCr in two quartiles with high UHg concentrations. The results
      indicated that human IHg exposure may cause impairment of renal function. By
      calculation of Probable Daily Intake from different routes, we found that dietary
      intake is the main pathway of IHg exposure for the local population, rather than
      inhalation of Hg vapor.

PMID- 25863594
TI  - Kidney function and blood pressure in preschool-aged children exposed to cadmium
      and arsenic--potential alleviation by selenium.
AB  - BACKGROUND: Early-life exposure to toxic compounds may cause long-lasting health
      effects, but few studies have investigated effects of childhood exposure to
      nephrotoxic metals on kidney and cardiovascular function. OBJECTIVES: To assess
      effects of exposure to arsenic and cadmium on kidney function and blood pressure
      in pre-school-aged children, and potential protection by selenium. METHODS: This
      cross-sectional study was part of the 4.5 years of age (range: 4.4-5.4 years)
      follow-up of the children from a supplementation trial in pregnancy (MINIMat) in
      rural Bangladesh, and nested studies on early-life metal exposures. Exposure to
      arsenic, cadmium and selenium from food and drinking water was assessed by
      concentrations in children's urine, measured by ICP-MS. Kidney function was
      assessed by the estimated glomerular filtration rate (eGFR, n=1106), calculated
      from serum cystatin C, and by kidney volume, measured by ultrasound (n=375).
      Systolic and diastolic blood pressure was measured (n=1356) after five minutes
      rest. RESULTS: Multivariable-adjusted regression analyzes showed that exposure to
      cadmium, but not arsenic, was inversely associated with eGFR, particularly in
      girls. A 0.5 ug/L increase in urinary cadmium among the girls (above spline knot
      at 0.12) was associated with a decrease in eGFR of 2.6 ml/min/1.73 m(2),
      corresponding to 0.2SD (p=0.022). A slightly weaker inverse association with
      cadmium was also indicated for kidney volume, but no significant associations
      were found with blood pressure. Stratifying on children's urinary selenium (below
      or above median of 12.6 ug/L) showed a three times stronger inverse association
      of U-Cd with eGFR (all children) in the lower selenium stratum (B=-2.8; 95% CI: 
      5.5, -0.20; p=0.035), compared to those with higher selenium (B=-0.79; 95% CI: 
      3.0, 1.4; p=0.49). CONCLUSIONS: Childhood cadmium exposure seems to adversely
      affect kidney function, but not blood pressure, in this population of young
      children in rural Bangladesh. Better selenium status appears to be protective.
      However, it is important to follow up these children to assess potential long
      term consequences of these findings.

PMID- 25863595
TI  - Changes in persistent organic pollutant levels from adolescence to young
      adulthood.
AB  - Elimination rates and their corresponding half-lives are conceptually important
      and intuitively accessible pharmacokinetic measures of toxicant elimination, but
      regression-based estimates are biased proportional to the degree of continuing
      (background) exposure. We propose an alternative estimator, the censored normal
      regression model, which uses all observations, but treats individuals whose
      initial level failed to exceed their follow-up level as censored observations to
      weight the regression estimates from those that declined between blood draws. In
      this manner, we derive the intrinsic elimination rate, the elimination rate free
      from ongoing exposure, as a parameter in a regression with an unobserved, latent
      dependent variable. We utilize sequential measurements of persistent organic
      pollutants (POPs) levels from adolescence to adulthood, a period of intense
      change in size and body composition, to quantify individual-level change within a
      community exposed to significant quantities of contaminants over an extended
      period of time. Although much research has been conducted on effects of POPs, far
      less attention has been given to vectors of intake and changes in toxicant levels
      during the life course. We apply exploratory factor analysis (EFA) to types and
      timing of consumption, along with physical behavioral characteristics, to
      identify a structure of seven underlying factors. Although several variables show
      factorial complexity, the latent constructs included an age/maturation and period
      related factor, a nutritional composite, consumption prior to pregnancy, fish and
      fowl consumed during pregnancy, factors distinguishing body mass and weight from
      height, and bottom-feeding fish consumption. Unadjusted and adjusted half-lives
      using the censored normal regression estimator, as well as estimated half-lives
      from conventional log concentration regressions, are reported for PCB groupings,
      specific congeners, p,p'-DDE, and HCB. 

PMID- 25863596
TI  - Segmental Transarterial Embolization in a Translational Rat Model of
      Hepatocellular Carcinoma.
AB  - PURPOSE: To develop a clinically relevant, minimally invasive technique for
      transarterial embolization in a translational rat model of hepatocellular
      carcinoma (HCC). MATERIALS AND METHODS: Oral diethylnitrosamine was administered
      to 53 male Wistar rats ad libitum for 12 weeks. Tumor induction was monitored
      using magnetic resonance imaging. Minimally invasive lobar or segmental
      transarterial embolization was performed through a left common carotid artery
      approach. Necropsy was performed to evaluate periprocedural mortality. Histologic
      analysis of tumors that received embolization was performed to assess percent
      tumor necrosis. RESULTS: Severe cirrhosis and autochthonous HCCs were
      characterized in a cohort of rats composed of two groups of rats identically
      treated with diethylnitrosamine with median survival times of 101 days and 105
      days (n = 10/group). A second cohort was used to develop minimally invasive
      transarterial embolization of HCCs (n = 10). In a third cohort, lobar
      embolization was successfully performed in 9 of 10 rats and demonstrated a high
      rate of periprocedural mortality (n = 5). Necropsy performed for periprocedural
      mortality after lobar embolization demonstrated extensive tissue necrosis within
      the liver (n = 3) and lungs (n = 2), indicating nontarget embolization as the
      likely cause of mortality. In a fourth cohort of rats, a segmental embolization
      technique was successfully applied in 10 of 13 rats. Segmental embolization
      resulted in a reduction in periprocedural mortality (P = .06) relative to
      selective embolization and a 19% increase in average tumor necrosis (P = .04).
      CONCLUSIONS: Minimally invasive, segmental embolization mimicking the currently
      applied clinical approach is feasible in a translational rat model of HCC and
      offers the critical advantage of reduced nontarget embolization relative to lobar
      embolization.

PMID- 25863597
TI  - Essential roles of Cdc42 and MAPK in cadmium-induced apoptosis in Litopenaeus
      vannamei.
AB  - Cadmium, one of the most toxic heavy metals in aquatic environments, has severe
      effects on marine invertebrates and fishes. The MAPK signaling pathway plays a
      vital role in stress responses of animals. The mitogen-activated protein kinase
      (MAPK) signaling pathway plays a vital role in animals' stress responses,
      including mediation of apoptosis induced by the Rho GTPase Cdc42. However, there
      is limited knowledge about its function in shrimps, although disorders
      exacerbated by environmental stresses (including heavy metal pollution) have
      caused serious mortality in commercially cultured shrimps. Thus, we probed roles
      of Cdc42 in Litopenaeus vannamei shrimps (LvCdc42) during cadmium exposure by
      inhibiting its expression using dsRNA-mediated RNA interference. The treatment
      successfully reduced expression levels of MAPKs (including p38, JNK, and ERK).
      Cadmium exposure induced significant increases in expression levels of LvCdc42
      and MAPKs, accompanied by reductions in total hemocyte counts (THC) and increases
      in apoptotic hemocyte ratios and ROS production. However, all of these responses
      were much weaker in LvCdc42-suppressed shrimps, in which mortality rates were
      higher than in controls. Our results suggest that the MAPK pathway plays a vital
      role in shrimps' responses to Cd(2+). They also indicate that LvCdc42 in shrimps
      participates in its regulation, and thus plays key roles in ROS production,
      regulation of apoptosis and associated stress responses. 

PMID- 25863598
TI  - Nortestosterone-derived synthetic progestogens do not activate the progestogen
      receptor of Murray-Darling rainbowfish (Melanotaenia fluviatilis) but are potent
      agonists of androgen receptors alpha and beta.
AB  - Synthetic progestogens derived from 19-nortestosterone can elicit a number of
      adverse effects in fish including decreased fecundity, altered hormone levels,
      disruption of normal breeding cycles, expression in females of male-specific
      biomarkers, development of male secondary sexual characteristics in females, and
      changes in the expression of steroidogenic genes. A recent in vitro study showed
      that a number of representatives from this class of progestins were potent
      agonists of fathead minnow androgen receptor (AR) and only weak agonists of
      progesterone receptor (PR) from the same species. This confirms that synthetic
      progestogens derived from 19-nortestosterone function as AR agonists in
      otomorphs, which express a single AR subtype. However, numerous perciformes are
      known to express two AR subtypes. We have recently shown that ARalpha and ARbeta
      from Murray-Darling rainbowfish (Melanotaenia fluviatilis) respond differently to
      certain androgens and anti-androgens. The goal of the present study was to
      determine concentration-response profiles for selected progestins in
      transactivation assays driven by rainbowfish ARalpha, ARbeta and PR in order to
      ascertain the relative potency of progestins against these receptors. As a means
      of confirming the expected activity of the progestins and reference compounds
      used in the study against human-derived receptors, we also established
      concentration-response relationships using transactivation assays driven by human
      PR and AR. We found that all five 19-nortestosterone-derived progestins tested
      were highly potent agonists of rainbowfish ARalpha, but that only four of the
      five progestins were potent agonists of rainbowfish ARbeta, with norgestimate
      exhibiting only weak activity against rainbowfish ARbeta. The spironolactone
      derived progestin, drospirenone, was not an agonist of rainbowfish ARalpha or
      ARbeta but was a weak agonist of rainbowfish PR. None of the 19-nortestosterone
      progestins activated rainbowfish PR. These findings confirm that the majority of
      19-nortestosterone-derived progestins are likely to elicit strong androgenic
      activity in teleosts, but that PR-mediated effects would be minimal. In species
      that express two AR subtypes similar to rainbowfish ARalpha and ARbeta,
      biological processes mediated by a specific subtype may be affected differently
      by progestins such as norgestimate. 

PMID- 25863599
TI  - Assessment of anti-factor Xa activity of heparin in binary parenteral nutrition
      admixtures for premature neonates.
AB  - An in vitro study was carried out to determine the anti-Xa activity of heparin in
      binary parenteral nutrition (BPN) admixtures for premature neonates in our
      neonatal intensive care unit (NICU) after a 24-hour infusion, as well as to
      assess drug interaction with a 50% glucose solution. Two types of bags were
      prepared: (1) BPN admixtures (composition defined in the NICU) including sodium
      heparin at 77 UI/mL and (2) bags containing only G50% with sodium heparin at 193
      UI/mL. The anti-Xa activity of heparin was measured in bags at T0, after the 24
      hour infusion and in eluates at the outlet of the infusion line after 24hours,
      using a validated chromogenic anti-Xa method. Comparisons of the mean
      concentration observed with the theoretical value for anti-Xa activity were
      performed with the Student t-test. Mean values of anti-Xa activity do not differ
      significantly from the values expected for all conditions. We found a slight
      variation in anti-Xa activity when infused over 24hours for both types of bags,
      with and without in-line filtration, showing that heparin remains stable during
      this infusion period in both BPN admixtures and G50%. 

PMID- 25863600
TI  - A comparison of emotion regulation strategies in response to craving cognitions:
      Effects on smoking behaviour, craving and affect in dependent smokers.
AB  - AIM: The effects of three emotion regulation strategies that targeted smoking
      related thoughts were compared on outcomes relevant to smoking cessation. METHOD:
      Daily smokers applied defusion (n = 25), reappraisal (n = 25) or suppression (n =
      23) to thoughts associated with smoking during a cue-induced craving procedure.
      Smoking behaviour, approach/avoidance behavioural bias, and subjective measures
      of experiential avoidance, craving, and affect were assessed during the
      experimental session, with additional behavioural and subjective outcomes
      assessed at 24 h and seven day follow-up. The influence of baseline group
      differences in smoking level and nicotine dependence were explored statistically.
      RESULTS: Defusion and reappraisal were associated with greater restraint in
      smoking behaviour in the immediate post-session period as well as reduction in
      smoking at seven day follow-up compared to suppression. Relative to suppression,
      reduced subjective craving was seen in the reappraisal group, and reduced
      experiential avoidance in the defusion group. Differences in approach/avoidance
      responses to smoking and neutral cues were observed only between the suppression
      and reappraisal groups. Although suppression was rated as lower in both
      credibility and strategy-expectancy compared to defusion and reappraisal, neither
      credibility nor expectancy mediated the effect of any strategy on changes in
      levels of smoking. CONCLUSION: Defusion and reappraisal produced similar benefits
      in smoking-related behavioural outcomes but, relative to suppression, were
      associated with distinctive outcomes on experiential avoidance and craving. The
      effects appear to be independent of perceived expectancy and credibility of the
      different strategies. Overall, the results suggest a role for reappraisal and
      defusion strategies in the development of psychological treatments for addiction
      related disorders.

PMID- 25863601
TI  - The Yin and Yang of support from significant others: Influence of general social
      support and partner support of avoidance in the context of treatment for social
      anxiety disorder.
AB  - Support from social networks is generally considered to protect against mental
      disorder but in some circumstances support for negative behaviours (such as
      avoidance) may be counterproductive. Given the critical interplay between social
      anxiety disorder and social interactions, it is surprising that the relationship
      of support from significant others to this disorder has received so little
      attention. The current study evaluated the reciprocal relationships between
      perceived social support and perceived partner support for avoidance behaviours
      (avoidance support) among a sample of 131 participants with social anxiety
      disorder who were assessed three times within the context of a treatment outcome
      study. A new measure of partner support for avoidance behaviours was developed,
      called the Avoidance Support Measure, and showed adequate internal consistency
      and construct validity. Correlations at baseline showed significant negative
      relationships between perceived social support and social anxiety and significant
      positive relationships between avoidance support and social anxiety. Path
      analysis showed that perceived social support at Times 1 and 2 negatively
      predicted future social anxiety at Times 2 and 3. On the other hand, only a
      single predictive relationship involving avoidance support was significant and
      showed that social anxiety at Time 1 positively predicted avoidance support at
      Time 2. These early results point to the different ways that support from
      significant others might relate to social anxiety and suggest that further work
      in this area may be fruitful. 

PMID- 25863602
TI  - Optimization of the canola oil based vitamin E nanoemulsions stabilized by food
      grade mixed surfactants using response surface methodology.
AB  - The objective of the present study was to prepare canola oil based vitamin E
      nanoemulsions by using food grade mixed surfactants (Tween:80 and lecithin; 3:1)
      to replace some concentration of nonionic surfactants (Tween 80) with natural
      surfactant (soya lecithin) and to optimize their preparation conditions. RBD
      (Refined, Bleached and Deodorized) canola oil and vitamin E acetate were used in
      water/vitamin E/oil/surfactant system due to their nutritional benefits and
      oxidative stability, respectively. Response surface methodology (RSM) was used to
      optimize the preparation conditions. The effects of homogenization pressure (75
      155MPa), oil concentrations (4-12% w/w), surfactant concentrations (3-11% w/w)
      and vitamin E acetate contents (0.4-1.2% w/w) on the particle size and emulsion
      stability were studied. RSM analysis has shown that the experimental data could
      be fitted well into second-order polynomial model with the coefficient of
      determinations of 0.9464 and 0.9278 for particle size and emulsion stability,
      respectively. The optimum values of independent variables were 135MPa
      homogenization pressure, 6.18% oil contents, 6.39% surfactant concentration and
      1% vitamin E acetate concentration. The optimized response values for particle
      size and emulsion stability were 150.10nm and 0.338, respectively. Whereas, the
      experimental values for particle size and nanoemulsion stability were 156.13+/
      2.3nm and 0.328+/-0.015, respectively. 

PMID- 25863603
TI  - Semi-synthesis of new antimicrobial esters from the natural oleanolic and
      maslinic acids.
AB  - In this article, we report an effective procedure for the selective isolation of
      oleanolic acid 1 and maslinic acid 2 (3.4 and 8.5mg/g DW, respectively) from
      pomace olive (Olea europaea L.) using an ultrasonic bath, and the synthesis of a
      series of new triterpenic acid esters. The compounds were characterized by their
      spectral data and were evaluated for their antimicrobial activity. Among the
      compounds tested, those having sulfur and chlorine atoms were found to be
      antibacterial. They showed activity against two Gram-positive bacteria
      Staphylococcus aureus and Enterococcus faecalis and two Gram-negative bacteria
      Escherichia coli and Pseudomonas aeruginosa (MICs within a range of 5-25MUg/mL).
      The fungus Penicillium italicum was found to be the most sensitive to both sulfur
      derivatives: (3beta)-3-((thiophene-2-carbonyl)oxy)-olean-12-en-28-oic acid (1a)
      (IZ=22mm) and (2alpha,3beta-2,3-bis((thiophene-2-carbonyl)oxy)olean-12-en-28-oic
      acid (2a) (IZ=24mm). 

PMID- 25863604
TI  - Potential changes in the allergenicity of three forms of peanut after thermal
      processing.
AB  - This study aimed to analyze the influence of thermal processing on the IgE
      binding properties of three forms of peanut, its effects in the content of
      individual allergens and IgE cross-linking capacity in effector cells of allergy.
      Three forms of peanut were selected and subjected to thermal processing.
      Immunoreactivity was evaluated by means of immunoblot or ELISA inhibition assay.
      Specific antibodies were used to identify changes in the content of the main
      allergens in peanut samples. The ability of treated peanut to cross-link IgE was
      evaluated in a basophil activation assay and Skin Prick Testing (SPT). The
      results showed that thermal/pressure treatments at specific conditions had the
      capacity to decrease IgE binding properties of protein extracts from peanut. This
      effect went along with an altered capacity to activate basophils sensitized with
      IgE from patients with peanut allergy and the wheal size in SPT. 

PMID- 25863605
TI  - An environment-friendly procedure for the high performance liquid chromatography
      determination of benzoic acid and sorbic acid in soy sauce.
AB  - A rapid, accurate and environment-friendly procedure has been developed for the
      HPLC-based determination of benzoic acid and sorbic acid contents in soy sauce. A
      C18 column served as the stationary phase, methanol-ammonium acetate buffer
      (0.02M) (30:70, v/v) was used as the mobile phase, the flow rate was 1mL/min, the
      UV detector was set at 225nm and cinnamic acid was selected as an internal
      standard. Under such optimized conditions, benzoic acid, sorbic acid and the
      internal standard were separated within 8.1min. This newly developed procedure
      also showed excellent recurrence, with a relative standard deviation of less than
      3% and recoveries were 96.1-104.3%. 

PMID- 25863606
TI  - Determination of flavonol glycosides in green tea, oolong tea and black tea by
      UHPLC compared to HPLC.
AB  - An UHPLC method for the determination of flavonol glycosides (FOG) from green and
      oolong tea vs. black tea has been developed for the first time. Sample clean-up
      method by means of polyamide column chromatography was optimized with multiple
      step elution. Using UHPLC and HPLC with gradient elution and photodiode array
      detection, eighteen FOG compounds were determined with the aid of electrospray
      tandem mass spectrometry. These FOG compounds were qualified on both UHPLC and
      HPLC, and this UHPLC method successfully separated rutin (quercetin-3-O
      rutinoside) and K-grg (kaempferol-3-O-glucorhamnoglucoside) while conventional
      HPLC method did not. The total amounts of FOG compounds in the tea samples were
      2.32-5.67g/kg dry weight (calculated as aglycones), and there is no significant
      difference for the total FOG content among green tea, oolong tea and black tea.
      However, kaempferol glycosides are more abundant in green teas, while oolong tea
      has more quercetin and myricetin glycosides. In black tea quercetin glycosides
      were most abundant. 

PMID- 25863607
TI  - Glycation of beta-lactoglobulin and antiglycation by genistein in different
      reactive carbonyl model systems.
AB  - Advanced glycation end products (AGEs), which are formed in beta-lactoglobulin
      (beta-lg) glycation systems via the Maillard reaction, have been implicated in
      diabetes-related long-term complications. In the present study, we found that
      reaction conditions, including temperature, time, pH, reactant type and molar
      ratio of beta-lg to a sugar/MGO/GO, can significantly affect the formation of
      AGEs. Using SDS-PAGE, we further demonstrated that genistein, a natural
      isoflavone found in a number of plants including soybeans and kudzu, can
      efficiently inhibit cross-links of the glycated beta-lg, and suppress the
      formation AGEs in a dose-dependent manner by trapping reactive dicarbonyl
      compounds. The products formed from genistein and methylglyoxal (MGO) in the beta
      lg-MGO assay were analyzed using LC/MS. Both mono-MGO and di-MGO adducts of
      genistein were detected with this method. 

PMID- 25863608
TI  - Electrophoresis characterisation of protein as a method to establish the
      entomological origin of stingless bee honeys.
AB  - Increasing production of stingless-bee honey and the prospect of broader marker
      for natural and organic products indicate the need to establish parameters to
      determinate the entomological origin and authenticity of honey. In this research,
      honeys of Apis mellifera, Melipona beecheii and Trigona spp. were collected in
      Yucatan, Mexico. Stingless-bee honeys contained more water and less total sugars
      and reducing sugars. SDS-PAGE patterns show distinctive bands for each kind of
      honey. The SDS-PAGE pattern of A. mellifera proteins honey showed three bands
      with molecular weights between 10.2 and 74.8kDa, there were five proteins bands
      in M. beecheii honey with molecular weights between 6.1 and 97.0kDa and nine for
      Trigona spp. proteins between 9.3 and 86.7kDa. Conventional physicochemical
      parameters along with electrophoresis profiles of stingless-bee honeys proteins
      could be an alternative for determination of entomological origin. 

PMID- 25863609
TI  - Polyphenoloxidase from Riesling and Dornfelder wine grapes (Vitis vinifera) is a
      tyrosinase.
AB  - Polyphenoloxidases (PPO) of the type-3 copper protein family are considered to be
      catecholoxidases catalyzing the oxidation of o-diphenols to their corresponding
      quinones. PPO from Grenache grapes has recently been reported to display only
      diphenolase activity. In contrast, we have characterized PPOs from Dornfelder and
      Riesling grapes which display both monophenolase and diphenolase activity.
      Ultracentrifugation and size exclusion chromatography indicated that both PPOs
      occur as monomers with Mr of about 38kDa. Non-reducing SDS-PAGE shows two bands
      of about 38kDa exhibiting strong activity. Remarkably, three bands up to 60kDa
      displayed only very weak PPO activity, supporting the hypothesis that the C
      terminal domain covers the entrance to the active site. Molecular dynamic
      analysis indicated that the hydroxyl group of monophenolic substrates can bind to
      CuA after the flexible but sterically hindering Phe 259 swings away on a
      picosecond time scale. 

PMID- 25863610
TI  - Novel liquid chromatography-mass spectrometry method for sensitive determination
      of the mustard allergen Sin a 1 in food.
AB  - Mustard is a condiment added to a variety of foodstuffs and a frequent cause of
      food allergy. A new strategy for the detection of mustard allergen in food
      products is presented. The methodology is based on liquid chromatography analysis
      coupled to mass spectrometry. Mustard allergen Sin a 1 was purified from yellow
      mustard seeds. Sin a 1 was detected with a total of five peptides showing a
      linear response (lowest LOD was 5ng). Sin a 1 was detected in mustard sauces and
      salty biscuit (19+/-3mg/kg) where mustard content is not specified. Sin a 1, used
      as an internal standard, allowed quantification of this mustard allergen in
      foods. A novel LC/MS/MS SRM-based method has been developed to detect and
      quantify the presence of mustard. This method could help to detect mustard
      allergen Sin a 1 in processed foods and protect mustard-allergic consumers. 

PMID- 25863611
TI  - Stability of oligosaccharides derived from lactulose during the processing of
      milk and apple juice.
AB  - The scientific evidence on the bioactivity of oligosaccharides from lactulose has
      encouraged us to study their physicochemical modifications during the processing
      of milk and apple juice. The carbohydrate fraction with a degree of
      polymerization ?3 was stable in milk heated at temperatures up to 100 degrees C
      for 30min and in apple juice heated up to 90 degrees C for 15min. An assessment
      of the Maillard reaction in heated milk pointed out a higher formation of
      furosine in milk with oligosaccharides from lactulose as compared to its
      counterpart without this ingredient, due to a higher presence of galactose. The
      organoleptic properties of juice with oligosaccharides from lactulose were
      acceptable and similar to those of apple juice with commercial
      galactooligosaccharides. The results presented herein demonstrate that
      oligosaccharides from lactulose can be used as prebiotic ingredients in a wide
      range of functional foods, including those intended for diabetics and lactose
      intolerant individuals. 

PMID- 25863612
TI  - Purification and structural analysis of membrane-bound polyphenol oxidase from
      Fuji apple.
AB  - Membrane-bound polyphenol oxidase (mPPO) in Fuji apple (Malus domestica Borkh.
      cv. Red Fuji) was purified and analyzed with a nanoelectrospray ionization mass
      spectrometer. The three-dimensional model and binding site of mPPO to 4-methyl
      catechol were also studied using molecular docking. mPPO was purified 54.41-fold
      using temperature-induced phase partitioning technique and ion exchange
      chromatography. mPPO had a molecular weight of 67.3kDa. Even though a significant
      level of homology was observed between mPPO and the soluble polyphenol oxidase in
      the copper binding sequence, there was another region, rich in histidine
      residues, which differed in 13 amino acids. The three-dimensional structure of
      mPPO consisted of six alpha-helices, two short beta-strands, and ten random
      coils. The putative substrate-binding pocket contained six polar or charged amino
      acids, His191, His221, Trp224, Trp228, Phe227, and Val190. Trp224 and Trp228
      formed hydrogen bonds with 4-methyl-catechol. 

PMID- 25863613
TI  - Assessment of white grape pomace from winemaking as source of bioactive
      compounds, and its antiproliferative activity.
AB  - The antiproliferative effects of a purified white grape pomace extract (PWGPE),
      as well as of some phenolic standards on colon cancer cells were examined. The
      phenolic composition of the PWGPE was determined by rapid resolution liquid
      chromatography/mass spectrometry (RRLC/MS). The PWGPE had 92.6, 43.3 and 6.01mg/g
      of flavanols, flavonols and phenolic acids, respectively and, along with pure
      catechin, epicatechin, quercetin and gallic acid, they were all found capable of
      inhibiting cellular proliferation. PWGPE (100MUg/ml) inhibited the proliferation
      of cells by 52.1% at 48h, whilst catechin, epicatechin, quercetin and gallic acid
      (60MUg/ml) inhibited growth by 65.2%, 62.2%, 81.0% and 71.0%, respectively, at
      72h. The PWGPE is an interesting source of phenolic compounds with
      antiproliferative properties, that could be of interest in the food and
      pharmaceutical industries. 

PMID- 25863614
TI  - Physical features, phenolic compounds, betalains and total antioxidant capacity
      of coloured quinoa seeds (Chenopodium quinoa Willd.) from Peruvian Altiplano.
AB  - Physical features, bioactive compounds and total antioxidant capacity (TAC) of
      coloured quinoa varieties (Chenopodium quinoa Willd.) from Peruvian Altiplano
      were studied. Quinoa seeds did not show a pure red colour, but a mixture which
      corresponded to different fractal colour values (51.0-71.8), and they varied from
      small to large size. Regarding bioactive compounds, total phenolic (1.23-3.24mg
      gallic acid equivalents/g) and flavonol contents (0.47-2.55mg quercetin
      equivalents/g) were highly correlated (r=0.910). Betalains content (0.15
      6.10mg/100g) was correlated with L colour parameter (r=-0.569), total phenolics
      (r=0.703) and flavonols content (r=0.718). Ratio of betaxanthins to betacyanins
      (0.0-1.41) was negatively correlated with L value (r=-0.744). Whereas, high TAC
      values (119.8-335.9mmol Trolox equivalents/kg) were negatively correlated with L
      value (r=-0.779), but positively with betalains (r=0.730), as well as with free
      (r=0.639), bound (r=0.558) and total phenolic compounds (r=0.676). Unexploited
      coloured quinoa seeds are proposed as a valuable natural source of phenolics and
      betalains with high antioxidant capacity. 

PMID- 25863615
TI  - Variation in nutritional compositions, antioxidant activity and microstructure of
      Lycopus lucidus Turcz. root at different harvest times.
AB  - The objective of this study was to investigate the variation in nutritional
      compositions, antioxidant activity and microstructure of Lycopus lucidus Turcz.
      root at different harvest times. L. lucidus Turcz. roots, harvested from two
      sites (S1 and S2) at three different times (T1: 19-11-2013, T2: 22-12-2013 and
      T3: 27-01-2014), were analyzed for nutritional compositions, antioxidant activity
      by DPPH, FRAP and TEAC assays and microstructure. The results revealed that the
      protein content in L. lucidus Turcz. root first decreased and then increased to a
      maximum at T3. The reducing sugar content had no significant differences among
      the three harvest dates studied. The starch content decreased drastically along
      with an increase of crude fat content with the harvest time delayed. The major
      amino acids in L. lucidus Turcz. root were aspartic acid and glutamate and the
      highest total amino acid content was found for the root harvested at T3. The most
      common element in L. lucidus Turcz. root was detected to be potassium followed by
      calcium, iron, magnesium, copper and manganese, and their changes were discrepant
      in the period of harvest. The FP and SGP possessed the highest and lowest
      phenolic content, respectively. The change of SEP was significantly correlated to
      the SGP at different harvest times. The highest TPC was found for the root
      harvested at T3 and the most abundant phenolic acid was chlorogenic acid. The
      highest and lowest DPPH radical scavenging capacity was observed for the SGP and
      FP, respectively. The highest and lowest FRAP and TEAC were observed for the FP
      and SGP, respectively. The results of correlation analysis indicated that there
      was significant correlation between phenolic content and FRAP and TEAC, and
      different antioxidant assays. The microstructure of L. lucidus Turcz. root also
      varied greatly with the harvest times. 

PMID- 25863616
TI  - Three differently generated salmon protein hydrolysates reveal opposite effects
      on hepatic lipid metabolism in mice fed a high-fat diet.
AB  - This study investigates the effects of salmon peptide fractions, generated using
      different enzymatic hydrolyzation methods, on hepatic lipid metabolism. Four
      groups of mice were fed a high-fat diet with 20% casein (control group) or 15%
      casein and 5% of peptide fractions (treatment groups E1, E2 and E4) for 6weeks.
      Weight gain was reduced in mice fed E1 and E4-diets compared to control, despite
      a similar feed intake. Reduced plasma and liver triacylglycerol levels in E1 and
      E4-mice were linked to reduced fatty acid synthase (FAS) activity and hepatic
      expression of lipogenic genes. By contrast, plasma and liver lipids increased in
      the E2 group, concomitant with increased hepatic FAS activity and Delta9
      desaturase gene expression. Shotgun lipidomics showed that MUFAs were
      significantly reduced in the E1 and E4 groups, whereas PUFAs were increased, and
      the opposite was observed in the E2 group. In conclusion, bioactive peptides with
      distinctive properties could potentially be isolated from salmon hydrolysates. 

PMID- 25863617
TI  - New haptens and antibodies for ractopamine.
AB  - In this work, three unreported immunizing haptens of ractopamine (RAC) were
      synthesized and used to produce highly sensitive and specific polyclonal
      antibody. The spacer arms of haptens for coupling to protein carrier were located
      on different position of RAC with different length. High affinity polyclonal
      antibodies were obtained and characterized in terms of titer and sensitivity by
      using enzyme-linked immunosorbent assay (ELISA). The best antibody employed in a
      heterologous competitive ELISA exhibited an IC50 value as low as 0.12ngmL(-1) and
      could not recognize other 10 beta-agonists including clenbuterol and salbutamol.
      The heterologous competitive ELISA was preliminary applied to swine urine and the
      results showed the new antibody was sufficiently sensitive and specific, and
      potentially used for the detection of RAC at trace level in real samples. 

PMID- 25863618
TI  - Stabilizing oil-in-water emulsions with regenerated chitin nanofibers.
AB  - Natural chitin is a highly crystalline biopolymer with poor aqueous solubility.
      Thus direct application of chitin is rather limited unless chemical modifications
      are made to improve its solubility in aqueous media. Through a simple dissolution
      and regeneration process, we have successfully prepared chitin nanofibers with
      diameters around 50nm, which form a stable suspension at concentrations higher
      than 0.50% and a self-supporting gel at concentrations higher than 1.00%.
      Additionally, these nanofibers can stabilize oil-in-water emulsions with oil
      fraction more than 0.50 at chitin usage level of 0.01g/g oil. The droplet sizes
      of the resulting emulsions decrease with increasing chitin concentrations and
      decreasing oil fraction. Confocal laser scanning micrographs demonstrate the
      adsorption of chitin nanofibers on the emulsion droplet surface, which indicates
      the emulsion stabilization is through a Pickering mechanism. Our findings allow
      the direct application of chitin in the food industry without chemical
      modifications. 

PMID- 25863619
TI  - Chlorophyta and Rhodophyta macroalgae: a source of health promoting
      phytochemicals.
AB  - A detailed study of the lipophilic composition of Codium tomentosum, Ulva
      lactuca, Gracilaria vermiculophylla and Chondrus crispus macroalgae cultivated in
      the Portuguese coast was carried out by gas chromatography-mass spectrometry
      before and after alkaline hydrolysis. Their long-chain aliphatic alcohols and
      monoglycerides compositions are reported for the first time. Additionally, other
      new compounds were also identified: phytol and neophytadiene in C. tomentosum, U.
      lactuca and G. vermiculophylla and stigmasterol, alpha-tocopherol and 24
      methylenecholesterol in C. tomentosum. The lipophilic fraction of the studied
      macroalgae are mainly constituted by fatty acids (110.1-1030.5mgkg(-1) of dry
      material) and sterols (14.8-1309.1mgkg(-1) of dry material). C. tomentosum showed
      to be a valuable source of stigmasterol (1229.0mgkg(-1) of dry material) and
      alpha-tocopherol (21.8mgkg(-1) of dry material). These results are a relevant
      contribution for the valorisation of these macroalgae species as sources of
      valuable phytochemicals. 

PMID- 25863620
TI  - Determination of reducing power and metal chelating ability of antioxidant
      peptides: revisited methods.
AB  - The purpose of this study was to improve two common tests used for antioxidant
      capacity measurements, i.e. the reducing power and chelating ability
      measurements, for appropriate comparisons between the molecules tested and chosen
      references, as the usual methods are often performed in a qualitative way rather
      than a quantitative way. After revision, it was then possible to determine an
      AERC indice (Ascorbate Equivalent Reducing Capacity) and a CECC (Carnosine
      Equivalent Chelating Capacity) or EECC (EDTA Equivalent Chelating Capacity)
      indice according to the standard chosen, by analogy to the TEAC indice (Trolox
      Equivalent Antioxidant Capacity) already used in many reported works to determine
      the free radical scavenging activity. Thus, the determination of these relative
      indices enables the comparison of antioxidative capacities obtained in various
      studies. The adaptation of these two tests to micro-scales and the calculation of
      AERC, EECC and CECC were performed on model peptides. 

PMID- 25863621
TI  - Influence of dried Hokkaido pumpkin and ascorbic acid addition on chemical
      properties and colour of corn extrudates.
AB  - The influence of Hokkaido pumpkin powder (PP) addition to corn grits at levels
      4%, 6%, and 8% and ascorbic acid (AA) addition at levels 0.5% and 1% was
      evaluated. Extrusion was done using a single-screw extruder at two temperature
      regimes: 135/170/170 degrees C (E1) and 100/150/150 degrees C (E2). Mathematical
      models that describe the influence of additives on the colour of extrudates were
      determined. Raw extrusion mixtures as well as obtained extrudates were tested for
      ascorbic acid, polyphenol, proteins, fat, crude fibre, ash and carotenoids
      content, and antioxidant activity. E1 extrusion regime acted favourably on
      polyphenols, crude fibre content, and antioxidant activity. It also caused higher
      fat degradation than E2 extrusion. Xanthophylls (lutein and zeaxanthin) were less
      sensitive to extrusion than carotenes (alpha-carotene, 9-cis-beta-carotene and 13
      cis-beta-carotene). Ascorbic acid was more sensitive to higher extrusion
      temperatures (49-76% degradation). It provided protection to carotenoids and
      consequently the colour of the extrudates. 

PMID- 25863622
TI  - Extraction and purification of beta-amylase from stems of Abrus precatorius by
      three phase partitioning.
AB  - The stems of Abrus precatorius were used to extract a beta-amylase enriched
      fraction. A three phase partitioning method and a Doehlert design with 3
      variables (ratio of crude extract/t-butanol, the ammonium sulphate saturation and
      pH) were used. The data was fitted in a second-order polynomial model and the
      parameters were optimized to enrich beta-amylase. Experimental responses for the
      modulation were recovery of activity and the purification factor. The optimal
      conditions were: a ratio of crude extract/t-butanol of 0.87 (v/v), saturation in
      ammonium sulphate of 49.46% (w/v) and a pH of 5.2. An activity recovery of 156.2%
      and a purification factor of 10.17 were found. The enriched enzyme was identified
      as a beta-amylase and its molecular weight was 60.1kDa. Km and Vmax values were
      79.37mg/ml and 5.13U/ml, respectively and the highest activity was registered at
      a temperature of 70 degrees C and a pH between 6 and 6.5. A significant
      stabilization of the beta-amylase was observed up to 65 degrees C. 

PMID- 25863623
TI  - Simultaneous determination of synthetic colorants in yogurt by HPLC.
AB  - This article reports on a method to determine synthetic dyes in yogurts and milk
      drinks. Initially a method for extraction of artificial dyes was developed to
      pretreat samples in order to extract most of the artificial colorants. Then, the
      colorants were analyzed by HPLC-PAD using gradient elutions. The method was
      linear in the range of 0.5-25mgL(-1) colorants (0.9991<R(2)<0.9998), with LOD of
      0.18-4.58MUgL(-1). The results recovery test on two levels ranged from 82% to
      115%. The reference solution of the analytes remained stable for 3months. In the
      yogurt samples analyzed, the dye E122 (1.4-11.75mgL(-1)) was found in most
      samples, followed by dye E123 (3.12 and 12.56mgL(-1)). All samples had
      concentrations below the maximum level allowed for use in yogurt (5-30mg/100g
      dyes). [corrected].

PMID- 25863624
TI  - Soymilk processing with higher isoflavone aglycone content.
AB  - The objective of this work was to optimise conversion of beta-glucoside
      isoflavones to aglycones in soymilk processing and to evaluate their thermal
      stability. The soymilk was assessed for time and temperature effects of
      incubating supplied to central composite design 2(2). The response functions were
      investigated for beta-glucosidase activity and isoflavone contents. The beta
      glucosidase activity was reduced through soybean slurry incubation at
      approximately 64 degrees C and 3.42h. Maximum conversion of beta-glucosides into
      isoflavone aglycones involved soaking the soybeans at 5 degrees C for 14h at a
      1:3 ratio (soybean:water, w:v), homogenising them at a 1:8 ratio (soybean
      soaked:water, w:v) and incubation at 50 degrees C for 2.7h. In evaluation of
      thermal stability of isoflavones in soymilk at 97 degrees C for 25min, the
      daidzein and genistein aglycone contents were maintained, the glycitein and beta
      glucosides contents increased and the malonylglucoside content decreased. 

PMID- 25863625
TI  - A rapid method for simultaneously determining ethanol and methanol content in
      wines by full evaporation headspace gas chromatography.
AB  - This work reports on a full evaporation headspace gas chromatographic (FE HS-GC)
      method for simultaneously determining the ethanol (EtOH) and methanol (MeOH)
      content in wines. A small sample (10MUL) was placed in a headspace sample vial,
      and a near-complete mass transfer of ethanol and methanol from the liquid sample
      to the vapor phase was obtained within three minutes at a temperature of 105
      degrees C, which allowed the measurement of the EtOH and MeOH content in the
      sample by GC. The results showed excellent precision and accuracy, as shown by
      the reproducibilities of 1.02% and 2.11% for EtOH and MeOH, respectively, and
      recoveries that ranged from 96.1% to 104% for both alcohols. The method is
      efficient, accurate and suitable for the determination of EtOH and MeOH in wine
      production and quality control. 

PMID- 25863626
TI  - Mango (Mangifera indica L.) by-products and their valuable components: a review.
AB  - The large amount of waste produced by the food industries causes serious
      environmental problems and also results in economic losses if not utilized
      effectively. Different research reports have revealed that food industry by
      products can be good sources of potentially valuable bioactive compounds. As
      such, the mango juice industry uses only the edible portions of the mangoes, and
      a considerable amount of peels and seeds are discarded as industrial waste. These
      mango by-products come from the tropical or subtropical fruit processing
      industries. Mango by-products, especially seeds and peels, are considered to be
      cheap sources of valuable food and nutraceutical ingredients. The main uses of
      natural food ingredients derived from mango by-products are presented and
      discussed, and the mainstream sectors of application for these by-products, such
      as in the food, pharmaceutical, nutraceutical and cosmetic industries, are
      highlighted. 

PMID- 25863627
TI  - Influence of harvesting technique and maceration process on aroma and phenolic
      attributes of Sauvignon blanc wine.
AB  - Sauvignon blanc wines are characterised by their varietal aromas and low phenolic
      content. Mechanical harvesting has been shown to increase several varietal
      aromas. Likewise, maceration techniques have produced increases in phenolic
      content and antioxidant activity, but these can also alter tactile attributes and
      sensory profiles. Mechanical harvesting and cryogenic maceration were used in
      combination to produce a Sauvignon blanc wine with increased phenolic content and
      antioxidant activity, while showing a similar sensory profile to control wines.
      Phenolic profiles of the wines showed differences between the harvesting and
      maceration techniques. Mechanical harvesting contributed to decreases in
      phenolics through reaction with oxidative radicals. Cryogenic maceration
      increased phenolics and antioxidant activity. Cryogenic maceration also increased
      the levels of several varietal aromas, for Sauvignon blanc wines made from both
      hand-picked and from machine-harvested fruit. Furthermore, cryogenic treatment of
      hand-picked fruit increased varietal thiols to levels similar to machine
      harvested control wines. 

PMID- 25863628
TI  - Antioxidant activity of alkyl gallates and glycosyl alkyl gallates in fish oil in
      water emulsions: relevance of their surface active properties and of the type of
      emulsifier.
AB  - The antioxidant activity of gallic acid and a series of alkyl gallates (C4-C18)
      and glycosylated alkyl gallates (C4-C18) on fish oil-in-water emulsions was
      studied. Three types of emulsifiers, lecithin, Tween-20 and sodium dodecyl
      sulphate (SDS) were tested. A nonlinear behavior of the antioxidant activity of
      alkyl gallates when increasing alkyl chain length was observed for emulsions
      prepared with lecithin. Medium-size alkyl gallates (C6-C12) were the best
      antioxidants. In contrast, for emulsions prepared with Tween-20, the antioxidants
      seem to follow the polar paradox. Glucosyl alkyl gallates were shown previously
      to be better surfactants than alkyl gallates. Nevertheless, they exhibited a
      worse antioxidant capacity than their corresponding alkyl gallates, in emulsions
      prepared with lecithin or Tween-20, indicating the greater relevance of having
      three OH groups at the polar head in comparison with having improved surfactant
      properties but just a di-ortho phenolic structure in the antioxidant. 

PMID- 25863629
TI  - Chemical composition of red, brown and green macroalgae from Buarcos bay in
      Central West Coast of Portugal.
AB  - Six representative edible seaweeds from the Central West Portuguese Coast,
      including the less studied Osmundea pinnatifida, were harvested from Buarcos bay,
      Portugal and their chemical characterization determined. Protein content, total
      sugar and fat contents ranged between 14.4% and 23.8%, 32.4% and 49.3% and 0.6
      3.6%. Highest total phenolic content was observed in Codium tomentosum followed
      by Sargassum muticum and O. pinnatifida. Fatty acid (FA) composition covered the
      branched chain C13ai to C22:5 n3 with variable content in n6 and n3 FA; low n6:n3
      ratios were observed in O. pinnatifida, Grateloupia turuturu and C. tomentosum.
      Some seaweed species may be seen as good sources of Ca, K, Mg and Fe,
      corroborating their good nutritional value. According to FTIR-ATR spectra, G.
      turuturu was associated with carrageenan seaweed producers whereas Gracilaria
      gracilis and O. pinnatifida were mostly agar producers. In the brown algae, S.
      muticum and Saccorhiza polyschides, alginates and fucoidans were the main
      polysaccharides found. 

PMID- 25863630
TI  - 5-Methoxytryptamine reacts with natural food flavour to produce 6-methoxy
      tetrahydro-beta-carbolines: in vitro investigation of their antioxidant and
      cytotoxicity properties.
AB  - Various 6-methoxytetrahydro-beta-carboline derivatives, namely BEN (6-methoxy-1
      phenyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole), ANI (6-methoxy-1-(4
      methoxyphenyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole), ACE (6-methoxy-1
      methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole) and VAN (2-methoxy-4-(6-methoxy
      2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-l)phenol), were prepared via the
      Maillard reaction using food flavours and 5-methoxytryptamine in aqueous medium
      and were investigated for their in vitro antioxidant and cytotoxicity properties.
      These derivatives were found to exhibit moderate antioxidant properties, based on
      a combination of DPPH, ABTS and FRAP assays. The results suggested that the
      Maillard reaction could be used to generate beta-carboline antioxidants. It was
      beneficial that VAN showed the highest antioxidant activity but the least
      cytotoxic activities on non-tumourous cell lines of NIH/3T3, CCD18-Co and B98-5
      using MTT assay. ACE, ANI and BEN showed mild toxicity at effective antioxidative
      concentrations derived from DPPH and ABTS assays. Furthermore, they are safer
      compared to 5-fluorouracil, cisplatin and betulinic acid on NIH/3T3, CCD18-Co and
      B98-5 cells. In conclusion, the antioxidant and cytotoxicity properties of 6
      methoxytetrahydro-beta-carbolines were demonstrated for the first time. 

PMID- 25863631
TI  - Preservation properties of in situ modified CaCO3-chitosan composite coatings.
AB  - To improve the dispersibility, hydrophilia constraints of primitive particle
      size, and reduce the economic cost, in situ modified CaCO3-chitosan composite
      coatings were prepared by tape-casting with different modifiers. The coating
      structures were characterised, and the preservation properties of the coatings
      were evaluated by fresh indices of Sciaenops ocellatus. The results revealed that
      the coatings were homogeneous and compact when the in situ modifier was sodium
      stearate. Besides, the amide I group of chitosan disappeared and hydrogen bonds
      were formed between the nano-CaCO3 and the chitosan. Meanwhile, the preservation
      effects to S. ocellatus of the coatings modified in situ by sodium stearate and
      sodium citrate were better. This was because the coatings effectively prevented
      oxygen and bacteria from reaching S. ocellatus, and thus inhibited the
      degradation of the proteins and lipids. The in situ modified method is conducive
      to chitosan coating properties, which will be widely used in the food
      preservation field. 

PMID- 25863632
TI  - Development of brewing science in (and since) the late 19th century: molecular
      profiles of 110-130year old beers.
AB  - The 19th century witnessed many advances in scientific enzymology and
      microbiology that laid the foundations for modern biotechnological industries. In
      the current study, we analyze the content of original lager beer samples from the
      1880s, 1890s and 1900s with emphasis on the carbohydrate content and composition.
      The historic samples include the oldest samples brewed with pure Saccharomyces
      carlsbergensis yeast strains. While no detailed record of beer pasteurization at
      the time is available, historic samples indicate a gradual improvement of bottled
      beer handling from the 1880s to the 1900s, with decreasing contamination by
      enzymatic and microbial activities over this time span. Samples are sufficiently
      well preserved to allow comparisons to present-day references, thus yielding
      molecular signatures of the effects of 20th century science on beer production.
      Opposite to rather stable carbohydrate profiles, some aldehydes reach up to 40
      fold higher levels in the historic samples as compared to present-day references.

PMID- 25863633
TI  - Plant derived and dietary phenolic antioxidants: anticancer properties.
AB  - In this paper, a review of the literature on the phenolic compounds with
      anticancer activity published between 2008 and 2012 is presented. In this
      overview only phenolic antioxidant compounds that display significant anticancer
      activity have been described. In the first part of this review, the oxidative and
      nitrosative stress relation with cancer are described. In the second part, the
      plant-derived food extracts, containing identified phenolic antioxidants, the
      phenolic antioxidants isolated from plants and plant-derived food or commercially
      available and the synthetic ones, along with the type of cancer and cells where
      they exert anticancer activity, are described and summarized in tables. The
      principal mechanisms for their anti-proliferative effects were also described.
      Finally, a critical analysis of the studies and directions for future research
      are included in the conclusion. 

PMID- 25863634
TI  - Ion-exchange equilibrium of N-acetyl-D-neuraminic acid on a strong anionic
      exchanger.
AB  - N-acetyl-D-neuraminic acid (Neu5Ac) is a high value-added product widely applied
      in the food industry. A suitable equilibrium model is required for purification
      of Neu5Ac based on ion-exchange chromatography. Hence, the equilibrium uptake of
      Neu5Ac on a strong anion exchanger, AD-1 was investigated experimentally and
      theoretically. The uptake of Neu5Ac by the hydroxyl form of the resin occurred
      primarily by a stoichiometric exchange of Neu5Ac(-) and OH(-). The experimental
      data showed that the selectivity coefficient for the exchange of Neu5Ac(-) with
      OH(-) was a non-constant quantity. Subsequently, the Saunders' model, which took
      into account the dissociation reactions of Neu5Ac and the condition of
      electroneutrality, was used to correlate the Neu5Ac sorption isotherms at various
      solution pHs and Neu5Ac concentrations. The model provided an excellent fit to
      the binary exchange data for Cl(-)/OH(-) and Neu5Ac(-)/OH(-), and an approximate
      prediction of equilibrium in the ternary system Cl(-)/Neu5Ac(-)/OH(-). This basic
      information combined with the general mass transfer model could lay the
      foundation for the prediction of dynamic behavior of fixed bed separation process
      afterwards.

PMID- 25863635
TI  - Allyl isothiocyanate enhances shelf life of minimally processed shredded cabbage.
AB  - The effect of allyl isothiocyanate (AITC), in combination with low temperature
      (10 degrees C) storage on post harvest quality of minimally processed shredded
      cabbage was investigated. An optimum concentration of 0.05MUL/mL AITC was found
      to be effective in maintaining the microbial and sensory quality of the product
      for a period of 12days. Inhibition of browning was shown to result from a down
      regulation (1.4-fold) of phenylalanine ammonia lyase (PAL) gene expression and a
      consequent decrease in PAL enzyme activity and o-quinone content. In the
      untreated control samples, PAL activity increased following up-regulation in PAL
      gene expression that could be linearly correlated with enhanced o-quinone
      formation and browning. The efficacy of AITC in extending the shelf life of
      minimally processed shredded cabbage and its role in down-regulation of PAL gene
      expression resulting in browning inhibition in the product is reported here for
      the first time. 

PMID- 25863636
TI  - Comparative in vitro fermentations of cranberry and grape seed polyphenols with
      colonic microbiota.
AB  - In this study, we have assessed the phenolic metabolism of a cranberry extract by
      microbiota obtained from the ascending colon and descending colon compartments of
      a dynamic gastrointestinal simulator (SHIME). For comparison, parallel
      fermentations with a grape seed extract were carried out. Extracts were used
      directly without previous intestinal digestion. Among the 60 phenolic compounds
      targeted, our results confirmed the formation of phenylacetic, phenylpropionic
      and benzoic acids as well as phenols such as catechol and its derivatives from
      the action of colonic microbiota on cranberry polyphenols. Benzoic acid
      (38.4MUg/ml), 4-hydroxy-5-(3'-hydroxyphenyl)-valeric acid (26.2MUg/ml) and
      phenylacetic acid (19.5MUg/ml) reached the highest concentrations. Under the same
      conditions, microbial degradation of grape seed polyphenols took place to a
      lesser extent compared to cranberry polyphenols, which was consistent with the
      more pronounced antimicrobial effect observed for the grape seed polyphenols,
      particularly against Bacteroides, Prevotella and Blautia coccoides-Eubacterium
      rectale. 

PMID- 25863637
TI  - Effects of long-term consumption of standard diets including glucose-lysine model
      glycated compounds on the antioxidant status of adult rats.
AB  - Our purpose was to evaluate the uptake of antioxidant capacity (AC) in rats fed
      long-term a diet containing commonly consumed Maillard reaction products (MRPs)
      from the glucose-lysine system. The effects on the oxidative status of liver,
      biceps brachii muscle and serum were also tested. The presence of model MRPs in
      the diet, especially melanoidins, led to a significantly higher intake
      (24.0MUmolTrolox/day), faecal excretion (0.604MUmolTrolox/day), and uptake
      (23.4MUmolTrolox/day) of AC, although the uptake rate remained stable compared to
      the control group (97.5%). Consumption of the assayed MRPs did not affect the
      hepatic antioxidant defence while some positive modifications, like an increase
      in glutathione peroxidase, were detected in muscle (29%) and serum (400%). This
      pointed to an improved antioxidant capacity. Despite the interesting findings for
      these specific MRPs, attention must be paid to the overall consumption of MRPs
      from different sources in a conventional diet, due to their implications in the
      development/advance of many disorders. 

PMID- 25863638
TI  - Monitoring the evolution of volatile compounds using gas chromatography during
      the stages of production of Moscatel sparkling wine.
AB  - This study reports, for the first time, the main changes that occur with some
      important aroma compounds of Moscatel sparkling wines during winemaking, measured
      using headspace solid-phase microextraction, one-dimensional and comprehensive
      two-dimensional gas chromatography (GC*GC) with mass spectrometry detection (MS).
      The best conditions of volatile extraction included the use of PDMS/DVB fibre,
      2mL of wine, 30% of NaCl, 40 degrees C for 30min. The chromatographic profile of
      sparkling wines showed decreasing amounts of monoterpenes (limonene, 4-terpineol,
      terpinolene, citronellol, alpha-terpineol, linalool, hotrienol, and nerol oxide),
      increasing amounts of esters (terpenyl esters, ethyl octanoate, ethyl decanoate
      and hexyl acetate) and alcohols (1-nonanol and 2-phenylethanol). Sixty-nine
      compounds co-eluted in the first dimension; only six co-eluted in the second
      dimension. GC*GC/TOFMS allows more detailed study of the volatile profile of
      sparkling wines. 

PMID- 25863639
TI  - Letter to the editor.

PMID- 25863640
TI  - Reply to the letter to the editor of Heather Greenfield.

PMID- 25863641
TI  - Experimental pulmonary fibrosis in rats with chronic gastric acid reflux
      esophagitis.
AB  - OBJECTIVE: To elucidate the association between gastric acid reflux and
      respiratory diseases by studying the histological changes of the lower airway in
      rats with chronic acid reflux esophagitis. METHODS: An experimental rat model of
      chronic acid reflux esophagitis was surgically created. The lower airways of
      these rats were histologically observed for more than 50 weeks. RESULTS: Although
      there were no histological changes which induced gastric acid reflux at 10 weeks
      after surgery, thickening of the basal laminae and the proliferation of the
      collagenous fibers were observed in the alveolar epithelium at 20 weeks after
      surgery. At 50 weeks after surgery, the collagenous fibers obliterated the
      pulmonary alveoli and bronchial lumen. These findings observed in the GERD rats
      are similar to the pathological findings of human pulmonary fibrosis. CONCLUSION:
      In this study, we reported pathological changes in the lower airways of GERD rat
      models observed for more than 50 weeks. These results suggest that gastric acid
      reflux may be one of the pathogenic or exacerbating factors of pulmonary
      fibrosis.

PMID- 25863642
TI  - Robot-assisted excision of branchial cleft cysts using a postauricular facelift
      approach.
AB  - Various approaches have been employed to avoid visible scars in the neck, along
      with the development of robotic and endoscopic techniques. We have employed a
      technique of robot-assisted excision of branchial cleft cyst (BCC) via a
      postauricular facelift approach. We present three patients with 2nd BCC who
      underwent robot-assisted excision of mass. All operations were performed
      successfully without complication. Postoperative cosmesis was excellent and all
      patients were satisfied with their scars which were concealed by hair and
      auricle. Robot-assisted excision of BCC is technically feasible and will be
      helpful for patients with BCC who wish to hide any visible scarring. 

PMID- 25863643
TI  - Prioritization of free-text clinical documents: a novel use of a bayesian
      classifier.
AB  - BACKGROUND: The amount of incoming data into physicians' offices is increasing,
      thereby making it difficult to process information efficiently and accurately to
      maximize positive patient outcomes. Current manual processes of screening for
      individual terms within long free-text documents are tedious and error-prone.
      This paper explores the use of statistical methods and computer systems to assist
      clinical data management. OBJECTIVE: The objective of this study was to verify
      and validate the use of a naive Bayesian classifier as a means of properly
      prioritizing important clinical data, specifically that of free-text radiology
      reports. METHODS: There were one hundred reports that were first used to train
      the algorithm based on physicians' categorization of clinical reports as high
      priority or low-priority. Then, the algorithm was used to evaluate 354 reports.
      Additional beautification procedures such as section extraction, text
      preprocessing, and negation detection were performed. RESULTS: The algorithm
      evaluated the 354 reports with discrimination between high-priority and low
      priority reports, resulting in a bimodal probability distribution. In all
      scenarios tested, the false negative rates were below 1.1% and the recall rates
      ranged from 95.65% to 98.91%. In the case of 50% prior probability and 80%
      threshold probability, the accuracy of this Bayesian classifier was 93.50%, with
      a positive predictive value (precision) of 80.54%. It also showed a sensitivity
      (recall) of 98.91% and a F-measure of 88.78%. CONCLUSIONS: The results showed
      that the algorithm could be trained to detect abnormal radiology results by
      accurately screening clinical reports. Such a technique can potentially be used
      to enable automatic flagging of critical results. In addition to accuracy, the
      algorithm was able to minimize false negatives, which is important for clinical
      applications. We conclude that a Bayesian statistical classifier, by flagging
      reports with abnormal findings, can assist a physician in reviewing radiology
      reports more efficiently. This higher level of prioritization allows physicians
      to address important radiologic findings in a timelier manner and may also aid in
      minimizing errors of omission.

PMID- 25863644
TI  - Long-term peri-implant bone level changes of non-vascularized fibula bone grafted
      edentulous patients.
AB  - Long-term results of reconstructions and prosthetic rehabilitation of patients
      presenting severely atrophied edentulous ridges remains a challenge for
      clinicians. Among the various available augmentation materials there is evidence
      that avascular fibula bone grafts possess a reliable resistance against
      resorption and may thus provide a valuable source to reduce the loss of vertical
      bone height after reconstruction of the severely atrophied mandible and maxilla.
      The purpose of the present study was to assess long-term crestal bone level
      stability in avascular fibula bone grafts. 8 edentulous female patients (average
      age 70.6 years) with Class-VI-atrophy and less than 5 mm residual bone volume
      received onlay-grafting with avascular fibula bone grafts and were monitored with
      a mean observation time of 133.7 months (121-186). A total of 39 implants were
      placed in the maxilla and mandible. Three patients received immediate and five
      patients delayed implant placement 3 months after grafting. All patients were
      provided with bar-retained dentures. Postoperative evaluation included clinical
      implant success (Buser) and radiographic examinations (orthopantomogram) to
      quantify crestal bone resorption. Grafting was successfully performed in all
      patients with no regrafting necessary. All implants but one, lost 2 years after
      abutment connection, remained successfully integrated and fulfilled the Buser
      criteria, rendering to a success rate of 97%. Mean bone resorption after 10 years
      was mesial 1.4 mm and distal 1.4 mm at each implant-site. Maximum bone resorption
      occurred between postoperative and first year, thereafter no significant
      resorption was measured in re-examinations up to 15 years. Avascular fibula
      grafts are a reliable bone graft for augmentation procedures in atrophied
      edentulous ridges. Dental implants that integrated in the autogenous fibular bone
      grafts showed a stable crestal peri-implant bone level up to 15 years after
      implant placement.

PMID- 25863645
TI  - A circuit for pupil orienting responses: implications for cognitive modulation of
      pupil size.
AB  - Pupil size, as a component of orienting, changes rapidly in response to local
      salient events in the environment, in addition to its well-known illumination
      dependent modulation. Recent research has shown that visual, auditory, or
      audiovisual stimuli can elicit transient pupil dilation, and the timing and size
      of the evoked responses are systematically modulated by stimulus salience.
      Moreover, weak microstimulation of the superior colliculus (SC), a midbrain
      structure involved in eye movements and attention, evokes similar transient pupil
      dilation, suggesting that the SC coordinates the orienting response which
      includes transient pupil dilation. Projections from the SC to the pupil control
      circuitry provide a novel neural substrate underlying pupil modulation by various
      cognitive processes. 

PMID- 25863646
TI  - Depersonalization: An exploratory factor analysis of the Italian version of the
      Cambridge Depersonalization Scale.
AB  - BACKGROUND: "Depersonalization" (DP) is a common symptom in the general
      population and psychiatric patients (Michal et al., 2011 [1]). DP is
      characterized by an alteration in the experience of the self, so that one feels
      detached from his or her own mental processes or body (or from the world),
      feeling as being an outside observer of his or her own self, and loosing the
      experience of unity and identity (American Psychiatric Association, 2013 [2]).
      AIM: We performed an exploratory factor analysis of the Cambridge
      Depersonalization Scale Italian version (CDS-IV). METHODS: We enrolled 149
      inpatients and outpatients of psychiatric services located in two Italian
      regions, Lazio and Campania. Patients were aged between 15 and 65 and diagnosed
      with schizophrenic, depressive or anxiety disorders. RESULTS: Four factors
      accounted for 97.4% of the variance. Factor 1 (10, 24, 26, 1, 13, 23, 9, 2, 5,
      and 11), called "Detachment from the Self", captures experiences of detachment
      from actions and thoughts. Factor 2 (19, 20, 27, 3, 12, 23, 22, and 11), called
      "Anomalous bodily experiences", refers to unusual bodily experiences. Factor 3
      (7, 28, 25, 6, 9, and 2), named "Numbing", describes the dampening of affects.
      Factor 4 (14, 17, and 16), named "Temporal blunting", refers to the subjective
      experience of time. We did not find any specific factor that refers to
      derealization; this suggests that the constructs of
      depersonalization/derealization (DP/DR) were strongly related to each other.
      CONCLUSIONS: Our results show that the constructs of DP/DR subsume several
      psychopathological dimensions; moreover, the above mentioned factors were broadly
      consistent with prior literature.

PMID- 25863647
TI  - Towards a framework for evaluating and grading evidence in public health.
AB  - The Project on a Framework for Rating Evidence in Public Health (PRECEPT) is an
      international collaboration of public health institutes and universities which
      has been funded by the European Centre for Disease Prevention and Control (ECDC)
      since 2012. Main objective is to define a framework for evaluating and grading
      evidence in the field of public health, with particular focus on infectious
      disease prevention and control. As part of the peer review process, an
      international expert meeting was held on 13-14 June 2013 in Berlin. Participants
      were members of the PRECEPT team and selected experts from national public health
      institutes, World Health Organization (WHO), and academic institutions. The aim
      of the meeting was to discuss the draft framework and its application to two
      examples from infectious disease prevention and control. This article introduces
      the draft PRECEPT framework and reports on the meeting, its structure, most
      relevant discussions and major conclusions. 

PMID- 25863649
TI  - A strategy by which to face the future.

PMID- 25863648
TI  - Cooked common beans (Phaseolus vulgaris L.) modulate renal genes in
      streptozotocin-induced diabetic rats.
AB  - Food consumption with different bioactive compounds could reduce the risk of
      diabetic complications. This study was designed to evaluate the effect of cooked
      common beans on differentially expressed genes in whole kidney homogenates of
      streptozotocin-induced diabetic rats. After 4weeks of treatment with a cooked
      bean supplemented (10%) diet, animals fed with Flor de Mayo bean (FMB) exerted
      the greatest protective effect, since they presented the lowest blood glucose
      levels, consistent with an increase in blood insulin levels, a decrease in urine
      albumin and urea levels and an increase in creatinine clearance (P<=.05).
      Regarding the gene expression of kidneys evaluated using expressed sequence tag,
      consumption of cooked beans improved the expression of Glu1, Cps1, Ipmk, Cacna1c,
      Camk1, Pdhb, Ptbp3 and Pim1, which are related to the elimination of ammonium
      groups, the regulation of inflammatory and oxidative response, as well as cell
      signaling and apoptosis. In addition, the beneficial effects observed were not
      related to their polyphenolic and saponin profile, suggesting the activity of
      other bioactive compounds or the synergistic interaction of these compounds.
      These results suggest that the consumption of cooked common beans (FMB) might be
      used as an alternative for the regulation of genes related to renal alterations. 

PMID- 25863650
TI  - Theory and practice in the construction of professional identity in nursing
      students: a qualitative study.
AB  - BACKGROUND: The problem of nurses' professional identity continues to be seen in
      the disjunction between theoretical training and clinical placements. Moreover,
      it is not known how nursing students perceive these contradictions or how this
      discrepancy influences the construction of professional identity. OBJECTIVE: To
      gain insight into nursing students' perception of their theoretical and practical
      training and how this training influences the process of constructing their
      professional identity. DESIGN: Qualitative, ethnographic study.
      PARTICIPANTS/SETTINGS: Third-year nursing students at the l'Escola Universitaria
      d'Infermeria Vall d'Hebron de Barcelona. METHODS: Participant observation was
      conducted in the hospital setting and primary care. Discussion groups were held.
      The constant comparative method was used for the analysis. The study adhered to
      the criteria of credibility, transferability, dependability and confirmability.
      RESULTS: Students believed that both theoretical and practical trainings were
      indispensable. Nevertheless, clinical placements were considered essential to
      confer sense to the theory and to shape their identity, as they helped student
      nurses to experience their future professional reality and to compare it with
      what they had been taught in theoretical and academic classes. The role of the
      clinical placement mentor was essential. With regard to theory, the skills
      developed in problem-based learning gave novice nurses' confidence to approach
      the problems of daily practice and new situations. Equally, this approach taught
      them to reflect on what they did and what they were taught and this ability was
      transferred to the clinical setting. CONCLUSIONS: For students, both strategies
      (theory and practice) are vital to nursing education and the construction of a
      professional identity, although pride of place is given to clinical placements
      and mentors. The skills developed with problem-based learning favor active and
      reflective learning and are transferred to learning in the clinical setting.

PMID- 25863651
TI  - Letter to the Editor.

PMID- 25863652
TI  - The complexity and challenges of the International Classification of Diseases,
      Ninth Revision, Clinical Modification to International Classification of
      Diseases, 10th Revision, Clinical Modification transition in EDs.
AB  - Beginning October 2015, the Center for Medicare and Medicaid Services will
      require medical providers to use the vastly expanded International Classification
      of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) system. Despite
      wide availability of information and mapping tools for the next generation of the
      ICD classification system, some of the challenges associated with transition from
      ICD-9-CM to ICD-10-CM are not well understood. To quantify the challenges faced
      by emergency physicians, we analyzed a subset of a 2010 Illinois Medicaid
      database of emergency department ICD-9-CM codes, seeking to determine the
      accuracy of existing mapping tools in order to better prepare emergency
      physicians for the change to the expanded ICD-10-CM system. We found that 27% of
      1830 codes represented convoluted multidirectional mappings. We then analyzed the
      convoluted transitions and found that 8% of total visit encounters (23% of the
      convoluted transitions) were clinically incorrect. The ambiguity and inaccuracy
      of these mappings may impact the workflow associated with the translation process
      and affect the potential mapping between ICD codes and Current Procedural Codes,
      which determine physician reimbursement. 

PMID- 25863653
TI  - Editorial: Ambulance Diversion: the Con Perspective.

PMID- 25863655
TI  - Should pregnancies be induced for impending macrosomia?

PMID- 25863654
TI  - Induction of labour versus expectant management for large-for-date fetuses: a
      randomised controlled trial.
AB  - BACKGROUND: Macrosomic fetuses are at increased risk of shoulder dystocia. We
      aimed to compare induction of labour with expectant management for large-for-date
      fetuses for prevention of shoulder dystocia and other neonatal and maternal
      morbidity associated with macrosomia. METHODS: We did this pragmatic, randomised
      controlled trial between Oct 1, 2002, and Jan 1, 2009, in 19 tertiary-care
      centres in France, Switzerland, and Belgium. Women with singleton fetuses whose
      estimated weight exceeded the 95th percentile, were randomly assigned (1:1), via
      computer-generated permuted-block randomisation (block size of four to eight) to
      receive induction of labour within 3 days between 37(+0) weeks and 38(+6) weeks
      of gestation, or expectant management. Randomisation was stratified by centre.
      Participants and caregivers were not masked to group assignment. Our primary
      outcome was a composite of clinically significant shoulder dystocia, fracture of
      the clavicle, brachial plexus injury, intracranial haemorrhage, or death. We did
      analyses by intention to treat. This trial is registered with ClinicalTrials.gov,
      number NCT00190320. FINDINGS: We randomly assigned 409 women to the induction
      group and 413 women to the expectant management group, of whom 407 women and 411
      women, respectively, were included in the final analysis. Mean birthweight was
      3831 g (SD 324) in the induction group and 4118 g (392) in the expectant group.
      Induction of labour significantly reduced the risk of shoulder dystocia or
      associated morbidity (n=8) compared with expectant management (n=25; relative
      risk [RR] 0.32, 95% CI 0.15-0.71; p=0.004). We recorded no brachial plexus
      injuries, intracranial haemorrhages, or perinatal deaths. The likelihood of
      spontaneous vaginal delivery was higher in women in the induction group than in
      those in the expectant management group (RR 1.14, 95% CI 1.01-1.29). Caesarean
      delivery and neonatal morbidity did not differ significantly between the groups.
      INTERPRETATION: Induction of labour for suspected large-for-date fetuses is
      associated with a reduced risk of shoulder dystocia and associated morbidity
      compared with expectant management. Induction of labour does not increase the
      risk of caesarean delivery and improves the likelihood of spontaneous vaginal
      delivery. These benefits should be balanced with the effects of early-term
      induction of labour. FUNDING: Assistance Publique-Hopitaux de Paris and the
      University of Geneva.

PMID- 25863656
TI  - Physiological Measures and Their Potential for the Assessment of Pediatric
      Hearing Needs.
AB  - PURPOSE: The purpose of this article is to discuss how cortical auditory evoked
      potentials might be used to assess speech perception capacity in infants,
      including acoustic change complex data collected in our laboratory. This article
      is a summary of a paper presented at the HEaring Across the Lifespan (HEAL)
      Conference held June 5-7, 2014, in Cernobbio, Italy. METHOD: Highlights from data
      collected in infants and the main issues needing investigation for clinical
      application are presented. CONCLUSIONS: Preliminary studies show promising
      results for the acoustic change complex and confirm that further inquiry into its
      clinical application is warranted. The presence of an onset response can be used
      clinically to confirm that auditory information has reached the cortex; however,
      the absence of a response cannot be interpreted with confidence.

PMID- 25863657
TI  - Antecedents of hospital nurses' intention to leave the organization: A cross
      sectional survey.
AB  - BACKGROUND: Leadership and perceived organizational support inspire trust in the
      leader and in the organization. Consequently, these aspects may contribute to a
      reduction in job burnout among nurses and, in the end, of the intention on their
      part to leave the hospital. It is crucial to develop models in order to
      simultaneously test the correlations between these relevant psychosocial
      variables, so that complexity of the nursing work environment may be better
      understood. OBJECTIVES: We expected to give support to and to further corroborate
      results in the literature linking perceived leadership style - and particularly
      servant leadership - perceived organizational support, trust in the leader and in
      the organization, job burnout among nurses and their subsequent intention to
      leave the hospital. DESIGN: Cross-sectional study. SETTING: Two Italian large
      size public hospitals. PARTICIPANTS: Two samples including both graduates and non
      graduates members of the nursing staff. Overall mean age was equal to 42.06 years
      while the general mean for tenure was 12.99 years. Data were collected in 2012.
      METHODS: A regression model with latent variables was tested via structural
      equation modeling using LISREL. The multi-sample procedure was also applied in
      order to test invariance of results between the two samples. RESULTS: Servant
      leadership was positively associated with trust in the leader and perceived
      organizational support was positively associated with trust in the organization.
      Trust in the leader and trust in the organization displayed a negative
      correlation with the emotional exhaustion and cynicism factors of job burnout,
      and a positive correlation with the professional efficacy factor. Furthermore,
      trust scores mediated the effects of servant leadership and perceived
      organizational support on job burnout factors. The cynicism factor was negatively
      associated with intention to leave the organization and it also mediated the
      effects of both trust in the leader and servant leadership on intention to leave.
      On the other hand, trust in the organization turned out to be directly and
      negatively related to intention to leave. CONCLUSIONS: Servant leadership and
      perceived organizational support showed their relevance in the nursing setting.
      The role of trust in the leader, trust in the organization and job burnout
      factors as mediating variables received support. Interestingly enough, the higher
      the cynicism score the higher the intention to leave the hospital. The results
      achieved may have practical implications not only for recruitment and training of
      nurse managers but also for hospital management.

PMID- 25863658
TI  - Medical language proficiency: A discussion of interprofessional language
      competencies and potential for patient risk.
AB  - In increasingly multilingual healthcare environments worldwide, ensuring
      accurate, effective communication is requisite. Language proficiency is
      essential, particularly medical language proficiency. Medical language is a
      universal construct in healthcare, the shared language of health and allied
      health professions. It is highly evolved, career-specific, technical and cultural
      bound-a language for specific purposes. Its function differs significantly from
      that of a standard language. Proficiency requires at minimum, a common
      understanding of discipline-specific jargon, abstracts, euphemisms,
      abbreviations; acronyms. An optimal medical language situation demands a level of
      competency beyond the superficial wherein one can convey or interpret deeper
      meanings, distinguish themes, voice opinion, and follow directions precisely. It
      necessitates the use of clarity, and the ability to understand both lay and
      formal language-characteristics not essential to standard language. Proficiency
      influences professional discourse and can have the potential to positively or
      negatively affect patient outcomes. While risks have been identified when there
      is language discordance between care provider and patient, almost nothing has
      been said about this within care teams themselves. This article will do so in
      anticipation that care providers, regulators, employers, and researchers will
      acknowledge potential language-based communication barriers and work towards
      resolutions. This is predicated on the fact that the growing interest in language
      and communication in healthcare today appears to be rested in globalization and
      increasingly linguistically diverse patient populations. Consideration of the
      linguistically diverse healthcare workforce is absent. An argument will be
      posited that if potential risks to patient safety exist and there are potentials
      for disengagement from care by patients when health providers do not speak their
      languages then logically these language-based issues can also be true for a care
      team of mixed linguistic backgrounds. Members may disengage from each other or
      adverse events may occur as a result of misunderstanding or other language-based
      confounds. While the greater goal of the article is to address the issues of
      medical language across languages, English and medical English are used to
      illustrate points. Questions will be posed to stimulate thought and identify a
      need for research. Recommendations include collaboration between the health and
      language disciplines. 

PMID- 25863659
TI  - An overview of management of root fractures.
AB  - Crown or root fractures are the most commonly encountered emergencies in the
      dental clinic. Root fractures occur in fewer than eight percent of the traumatic
      injuries to permanent teeth. They are broadly classified as horizontal and
      vertical root fractures. Correct diagnosis of root fractures is essential to
      ensure a proper treatment plan and hence, the best possible prognosis. Indication
      of the type of treatment to be used depends primarily on the level of the
      fracture line. Therefore, a clinician must also have a thorough knowledge of the
      various treatment approaches to devise a treatment plan accordingly. Various
      treatment strategies have been proposed, each with their own advantages and
      disadvantages. Hence, this literature review presents an overview of the various
      types of root fractures and their management. 

PMID- 25863660
TI  - The effect of psychostimulants on skeletal health in boys co-treated with
      risperidone.
AB  - OBJECTIVES: To examine the skeletal effects of chronic psychostimulant treatment
      in children and adolescents. STUDY DESIGN: Medically healthy 5- to 17-year-old
      males from 4 different clinic-based studies were combined for this analysis. They
      were divided by psychostimulant use into 3 groups: none to negligible,
      intermittent, and continuous use. Most (95%) had also received risperidone for 6
      months or more. Treatment history was extracted from medical and pharmacy
      records. Anthropometric and bone measurements, using dual-energy x-ray
      absorptiometry and peripheral quantitative computed tomography, were obtained at
      each research visit. Multivariable linear regression analysis models examined
      whether age-sex-specific height Z-score and skeletal outcomes differed among the
      3 psychostimulant-use groups. RESULTS: The sample consisted of 194 males with a
      mean age of 11.7 +/- 2.8 years at study entry. The majority had an externalizing
      disorder. There was no significant difference across the 3 treatment groups in
      height Z-score or in skeletal outcomes at the radius, lumbar spine, or whole
      body. One hundred forty-four boys had valid follow-up skeletal data 1.4 +/- 0.7
      years after study entry. Again, neither height Z-score nor the skeletal outcomes
      were different among those who remained on psychostimulants between the 2 visits,
      started psychostimulants anew, or had not taken psychostimulants. CONCLUSIONS:
      Following chronic treatment, psychostimulants did not appear to significantly
      affect bone mass accrual in children and adolescents taking risperidone. There
      was a small, but statistically not significant, negative impact on longitudinal
      growth.

PMID- 25863661
TI  - Safety of Early High-Dose Recombinant Erythropoietin for Neuroprotection in Very
      Preterm Infants.
AB  - OBJECTIVE: To investigate the safety and short term outcome of high dose
      recombinant human erythropoietin (rhEpo) given shortly after birth and
      subsequently over the first 2 days for neuroprotection to very preterm infants.
      STUDY DESIGN: Randomized, double masked phase II trial. Preterm infants
      (gestational age 26 0/7-31 6/7 weeks) were given rhEpo (nt = 229; 3000 U/kg body
      weight) or NaCl 0.9% (nc = 214) intravenously at 3, 12-18, and 36-42 hours after
      birth. RESULTS: There were no relevant differences between the groups for short
      term outcomes such as mortality, retinopathy of prematurity, intraventricular
      hemorrhage, sepsis, necrotizing enterocolitis, and bronchopulmonary dysplasia. At
      day 7-10, we found significantly higher hematocrit values, reticulocyte, and
      white blood cell counts, and a lower platelet count in the rhEpo group.
      CONCLUSIONS: Early high-dose rhEpo administration to very premature infants is
      safe and causes no excess in mortality or major adverse events. TRIAL
      REGISTRATION: ClinicalTrials.gov: NCT00413946.

PMID- 25863662
TI  - Prenatal Second-Hand Smoke Exposure Measured with Urine Cotinine May Reduce Gross
      Motor Development at 18 Months of Age.
AB  - OBJECTIVE: To evaluate the association of second-hand smoke exposure of pregnant
      mothers using urine cotinine with the neurodevelopment of their children at 18
      months of age in the mother-child cohort in Crete (Rhea Study). STUDY DESIGN:
      Selected participants were Greek mothers with singleton pregnancies, had never
      smoked, and had available urine cotinine measurements in pregnancy, and their
      children for whom a neurodevelopmental assessment was completed. We performed
      face-to-face interviews twice during pregnancy and postnatally, and assessed
      children's neurodevelopment at 18 months of age using the Bayley Scales of Infant
      and Toddler Development, Third Edition. We used linear regression and generalized
      additive models. RESULTS: Of 599 mothers, 175 (29%) met the inclusion criteria.
      Maternal urine cotinine levels were low (mean: 10.3 ng/mL, SD: 11.7 ng/mL).
      Reported passive smoking from different sources was strongly associated with
      urine cotinine levels. A negative association was observed between cotinine
      levels in pregnancy and child's gross motor function (beta = -3.22 per 10 ng/mL,
      95% CI -5.09 to -1.34) after adjusting for factors potentially associated with
      neurodevelopment; results were similar in both sexes. A negative association was
      also observed for cognitive and receptive communication scales but the effect was
      small and not statistically significant. CONCLUSIONS: Maternal exposure during
      pregnancy to second-hand smoke measured through urine cotinine was associated
      with a decrease in gross motor function among 18-month-old children, even at low
      levels of exposure.

PMID- 25863663
TI  - A Neonate with Acute Heart Failure: Chromosomally Integrated Human Herpesvirus 6
      Associated Dilated Cardiomyopathy.

PMID- 25863664
TI  - Heart failure management in skilled nursing facilities: a scientific statement
      from the American Heart Association and the Heart Failure Society of America.

PMID- 25863665
TI  - Chemotherapy-induced peripheral neuropathy (CIPN) and vitamin B12 deficiency.

PMID- 25863666
TI  - Bone health in type 1 diabetes: focus on evaluation and treatment in clinical
      practice.
AB  - INTRODUCTION: Type 1 diabetes (T1D) is an autoimmune disease with chronic
      hyperglycemic state, which incidence has been globally rising during the past
      decades. Besides the well-known diabetic complications such as retinopathy,
      nephropathy and neuropathy, T1D is characterized also by poor bone health. The
      reduced bone mineralization, quality and strength lead to vertebral and hip
      fractures as the most important clinical manifestations. Suppressed bone turnover
      is the main characteristic of T1D-associated bone disorder. RESULTS: This is
      thought to be due to hyperglycemia, hypoinsulinemia, autoimmune inflammation, low
      levels of insulin-like growth factor-1 and vitamin D. Young age of T1D
      manifestation, chronic poor glycemic control, high daily insulin dose, low body
      mass index, reduced renal function and the presence of diabetic complications are
      clinical factors useful for identifying T1D patients at risk of reduced bone
      mineral density. Although the clinical risk factors for fracture risk are still
      unknown, chronic poor glycemic control and the presence of diabetic complications
      might raise the suspicion of elevated fracture risk in T1D. In the presence of
      the above-mentioned risk factors, the assessment of bone mineral density by dual
      energy X-ray absorptiometry and the search of asymptomatic vertebral fracture by
      vertebral fracture assessment or lateral X-ray radiography of thorax-lumbar spine
      should be recommended. CONCLUSION: There is no consensus about the treatment of
      diabetic bone disorder. However, the improvement of glycemic control has been
      suggested to have a beneficial effect on bone in T1D. Recently, several
      experiments showed promising results on using anabolic pharmacological agents in
      diabetic rodents with bone disorder. Therefore, randomized clinical trials are
      needed to test the possible use of the bone anabolic therapies in humans with
      T1D.

PMID- 25863667
TI  - Streptomyces gilvigriseus sp. nov., a novel actinobacterium isolated from
      mangrove forest soil.
AB  - A novel Streptomyces, strain MUSC 26(T), was isolated from mangrove soil at
      Tanjung Lumpur, Malaysia. The bacterium was observed to be Gram-positive and to
      form grayish yellow aerial and substrate mycelium on ISP 7 agar. A polyphasic
      approach was used to study the taxonomy of strain MUSC 26(T), which shows a range
      of phylogenetic and chemotaxonomic properties consistent with those of the
      members of the genus Streptomyces. The cell wall peptidoglycan was determined to
      contain LL-diaminopimelic acid. The predominant menaquinones were identified as
      MK-9 (H8) and MK-9(H6). The polar lipids detected were identified as
      diphosphatidylglycerol, phosphatidylinositol, phosphatidylethanolamine,
      hydroxyphosphatidylethanolamine, phosphatidylmethylethanolamine and
      hydroxyphosphatidylmethylethanolamine. The predominant cellular fatty acids
      (>10.0 %) were identified as anteiso-C15:0 (31.4 %), iso-C16:0 (16.3 %), iso
      C15:0 (13.9 %) and anteiso-C17:0 (12.6 %). The cell wall sugars were found to be
      galactose, glucose, mannose, ribose and rhamnose. These results suggest that MUSC
      26(T) should be placed within the genus Streptomyces. Phylogenetic analysis
      indicated that closely related strains include Streptomyces qinglanensis
      172205(T) (96.5 % sequence similarity), S. sodiiphilus YIM 80305(T) (96.5 %) and
      S. rimosus subsp. rimosus ATCC 10970(T) (96.4 %). DNA-DNA relatedness values
      between MUSC 26(T) and closely related type strains ranged from 17.0 +/- 2.2 to
      33.2 +/- 5.3 %. Comparison of BOX-PCR fingerprints indicated MUSC 26(T) presents
      a unique DNA profile. The DNA G+C content was determined to be 74.6 mol%. Based
      on this polyphasic study of MUSC 26(T), it is concluded that this strain
      represents a novel species, for which the name Streptomyces gilvigriseus sp. nov.
      is proposed. The type strain is MUSC 26(T) (=DSMZ 42173(T) = MCCC 1K00504(T)). 

PMID- 25863668
TI  - Mangrovibacterium marinum sp. nov., isolated from a coastal sediment.
AB  - A Gram-stain negative, facultatively anaerobic, non-motile and rod shaped
      bacterium, designated FA423(T), was isolated from a marine sediment obtained off
      the coast of Weihai, China. Strain FA423(T) was found to grow at 17-42  degrees C
      (optimum, 33  degrees C) and pH 5.5-8.0 (optimum, 7.0-7.5) in the presence of 0.5
      6.0 % (w/v) NaCl (optimum, 1.0-2.0 %). Cells were found to be catalase positive
      and oxidase negative. Phylogenetic analysis of its 16S rRNA gene sequence
      revealed that strain FA423(T) is a member of the genus Mangrovibacterium and
      exhibits the highest sequence similarity (95.9 %) to the type strain of
      Mangrovibacterium diazotrophicum. The dominant cellular fatty acids were
      identified as summed feature 4 (iso-C17:1 I and/or anteiso-C17:1 B) and iso
      C15:0. Menaquinone MK-7 was found to be the sole respiratory quinone. The major
      polar lipids were found to be an unidentified lipid and an unidentified
      phospholipid. The DNA G+C content of strain FA423(T) is 47.4 mol%. Based on the
      phylogenetic and phenotypic characteristics, strain FA423(T) is considered to
      represent a novel species of the genus Mangrovibacterium, for which the name
      Mangrovibacterium marinum sp. nov. is proposed. The type strain is FA423(T) (=DSM
      28823(T) = KCTC 42253(T) = CICC 10903(T)). 

PMID- 25863669
TI  - The impact of infarct size on regional and global left ventricular systolic
      function: a cardiac magnetic resonance imaging study.
AB  - Myocardial infarction (MI) results in myocardial scarring which can have an
      impact on left ventricular (LV) stiffness and contractile function, ultimately
      leading to reduced LV systolic function and LV remodelling, However some concerns
      about the relation between scar extension and segmental wall motion contractility
      is not enough clear. Thus, the association between myocardial scar, LV regional
      and global function and LV remodeling should be investigated. We studied the
      relationship between scar extension, wall motion score index (WMSI), LV
      dimensions and systolic function in a group of patients with previous MI by
      cardiac magnetic resonance (CMR). 133 patients with previous (>6 month) MI were
      retrospectively enrolled in the study. Indexed end-systolic volume (ESVi),
      indexed end-diastolic volume (EDVi), LV ejection fraction (EF), stroke volume
      (SV), LV mass were measured using CMR. WMSI and sum scar score (SSS) were also
      measured following AHA?ACC criteria giving an arbitrary cut-off to distinguish
      larger from restricted late gadolinium enhancement (LGE) area. A total of 2261
      segments were studied: regional wall motion abnormalities were present in 1032
      segments (45%) and 724 (32%) showed presence of MI (LGE). WMSI correlated
      significantly with EF (r = -0.87, p < 0.0001) in all patients and in both
      patients with EF >= 40% (r = -0.77, p < 0.0001) and EF < 40% (r = -0.68, p <
      0.0001). WMSI also correlated significantly with SSS (r = 0.57, p < 0.0001). The
      correlation between WMSI and SSS was more significant in patients with transmural
      MI (WMSI 2.1 +/- 0.5 and SSS 17 +/- 8; r = 0.55, p < 0.0001) than with non
      transmural MI (WMSI 1.6 +/- 0.7 and SSS 6 +/- 4; r = 0.34 and p = 0.02). A
      significant correlation was also found between EF and SSS (r = -0.55 and p <
      0.0001) and between SSS and LV indexed volumes (EDVi; r = 0.44, p < 0.0001 and
      ESVi; r = 0.51, p < 0.0001). Infarct transmurality and extension as expressed as
      SSS assessed with cardiac MRI has an impact on global and regional systolic
      function. A multi-parametric score measuring WMSI scar transmurality and
      extension, could better identify an increased cardiac remodeling after coronary
      event.

PMID- 25863670
TI  - The progression of corrected myopia.
AB  - PURPOSE: This study seeks to demonstrate the existence of a feedback loop
      controlling myopia by comparing the prediction of a feedback model to the actual
      progression of corrected myopia. In addition to theoretical results, confirming
      clinical data are presented. METHODS: The refraction of 13 continuously corrected
      myopic eyes was collected over a period of time ranging from 4 to 9 years from
      the time of their first correction. Refractive data was collected in an optometry
      office from myopic young subjects from the general population in Boston. Subjects
      were myopes, ages 2 to 22 at the time of first correction selected randomly from
      a larger population. All individuals were fully corrected with lenses; new lenses
      were prescribed every time that their myopia increased by 0.25 diopters or more.
      Subjects wore their spectacle lenses during the followed period. RESULTS:
      Subjects exhibit a linear time course of myopia progression when corrected with
      lenses. The observed rate of myopia increase is 0.2 to 1.0 diopters/year, with a
      mean correlation coefficient r  = -0.971, p < 0.005. CONCLUSIONS: This report
      establishes that feedback control theory applies to the clinical phenomenon of
      progressive myopia. Continuous correction of myopia results in a linear
      progression that increases myopia. The Laplace transformation of temporal
      refractive data to the s-domain simplifies the study of myopia and emmetropia.
      The feedback transfer function predicts that continuous correction of myopia
      results in a linear progression because continuous correction opens the feedback
      loop. This prediction is confirmed with all subjects.

PMID- 25863671
TI  - Longitudinal analysis of the structural pattern of pseudophakic cystoid macular
      edema using multimodal imaging.
AB  - PURPOSE: To describe the relationship between pseudophakic cystoid macular edema
      (CME) progression and retinal structural changes observed by spectral-domain
      optical coherence tomography (SD-OCT) and fluorescein angiography. METHODS:
      Retrospective, consecutive, longitudinal imaging analysis of patients with acute
      pseudophakic cystoid macular edema. Two observers at two study centers evaluated
      all images and categorized the macular structural features based on the retinal
      layer involved with cystic changes and/or subretinal fluid. A time series of the
      structural pattern and visual acuity was constructed for 1-month intervals over a
      6-month study period. RESULTS: Thirty nine patients presented with CME. The mean
      time since cataract extraction was 48 +/-38 days (range 5-71). CME included inner
      nuclear layer (INL) cystic changes, outer plexiform layer (OPL) cystic changes,
      and subretinal fluid. Isolated INL changes were observed in four phakic fellow
      eyes. Isolated OPL morphology was not observed, and additional inner layers
      remained uninvolved. Resolution occurred rapidly following administration of
      periocular glucocorticoids, and typically demonstrated a reverse structural
      pattern or delayed subretinal fluid resolution. Isolated subretinal fluid or a
      combined INL and subretinal fluid structure indicated CME resolution. CONCLUSION:
      Acute and recurrent pseudophakic CME involves a directional progression of the
      retinal layer involved with cystic changes and a clinical course. CME begins with
      INL cystic changes, progresses to combined INL and OPL morphology, and may
      continue to involve subretinal fluid. The inner nuclear layer is the most
      frequently involved layer, and isolated INL cysts may occur in phakic fellow
      eyes. A three-layer structure, the presence of OPL morphology, or isolated INL
      early in the postoperative period indicates disease activity.

PMID- 25863673
TI  - Analysis of the ganglion cell layer and photoreceptor layer using optical
      coherence tomography after idiopathic epiretinal membrane surgery.

PMID- 25863672
TI  - The effect of nifedipine on retinal venous pressure of glaucoma patients with the
      Flammer-Syndrome.
AB  - PURPOSE: The purpose was to measure the retinal venous pressure (RVP) in both
      eyes of primary open-angle glaucoma (POAG) patients before and 3 weeks after
      treatment with low-dosed Nifedipine. METHODS: This retrospective study included
      20 POAG patients who were treated with Nifedipine (5 mg daily) and 20 untreated
      control POAG patients. In both the treated and untreated control group, a
      distinction was made between those patients who had the Flammer-Syndrome (FS) and
      those who did not. The RVP was measured in all patients bilaterally at baseline
      and 3 weeks later by means of contact lens ophthalmodynamometry and the RVP
      measurements of the treated POAG patients were compared to the RVPs of the
      untreated POAG controls. Ophthalmodynamometry is done by applying an increasing
      force on the eye via a contact lens. The minimum force required to induce a
      venous pulsation is called the ophthalmodynamometric force (ODF). The RVP is
      defined and calculated as the sum of ODF and intraocular pressure (IOP) [RVP =
      ODF + IOP]. RESULTS: The RVP decreased significantly after 3 weeks in both eyes
      of patients treated with low-dosed Nifedipine compared to the untreated group
      (mean decrease of 12.5 mmHg (SD 12.5), P < 0.001). A larger response to therapy
      was found in patients with the FS compared to patients lacking the FS (mean
      decrease of 16.07 vs. 7.28 mmHg, confidence Interval (CI): 5.2 to 9.3 vs. 12.3 to
      19.7; P < 0.001). No significant differences were accounted for in the IOP's of
      the patients after treatment. In the untreated control group, no significant
      differences were accounted for either in the RVP or the IOP after 3 weeks.
      CONCLUSIONS: Treatment with low-dosed Nifedipine decreases RVP in both eyes of
      glaucoma patients, particularly in those with the Flammer-Syndrome. This effect
      may be due to the partial inhibition of Endothelin-1 (ET-1) by Nifedipine.

PMID- 25863674
TI  - Axonal protection by brimonidine with modulation of p62 expression in TNF-induced
      optic nerve degeneration.
AB  - PURPOSE: The p62, also called sequestosome 1 (SQSTM1), plays a crucial role in
      tumor necrosis factor (TNF)-induced optic nerve degeneration. Brimonidine has
      been shown to have protective effects on retinal ganglion cell bodies, although
      its role in their axons remains to be examined. We determined whether brimonidine
      modulates axonal loss induced by TNF and affects the expression of p62 in the
      optic nerve. METHODS: Experiments were performed on adult male Wistar rats that
      received an intravitreal injection of 10 ng TNF alone or simultaneous injection
      of TNF and 2, 20, or 200 pmol of brimonidine tartrate. The expression of p62 in
      the optic nerve was examined by immunoblot analysis. The effects of brimonidine
      on axons were evaluated by counting axon numbers 2 weeks after intravitreal
      injection. RESULTS: Intravitreal injection of brimonidine exerted substantial
      axonal protection against TNF-induced optic nerve degeneration. Immunoblot
      analysis showed that p62 was upregulated in the optic nerve after intravitreal
      injection of TNF, and that this increase was completely inhibited by brimonidine.
      Treatment with brimonidine alone also significantly decreased p62 protein levels
      in the optic nerve compared with the basal level. CONCLUSIONS: These results
      suggest that the modulation of p62 levels in the optic nerve by brimonidine may
      be involved partly in its axonal protection.

PMID- 25863676
TI  - Flexible ureteroscopy and lasertripsy (FURSL) for paediatric renal calculi:
      Results from a systematic review.

PMID- 25863675
TI  - Effect of posterior vitreous detachment on aqueous humor level of vascular
      endothelial growth factor in exudative age-related macular degeneration patients.
AB  - BACKGROUND: To investigate the association of posterior vitreous detachment (PVD)
      with aqueous levels of vascular endothelial growth factor (VEGF) in eyes with
      exudative age-related macular degeneration (AMD). METHODS: This is a prospective
      comparative study. Subjects are 33 eyes with exudative AMD. PVD was examined by B
      mode ultrasonography and the subjects were divided into a complete PVD group (PVD
      group) or a group with partial or no PVD (without PVD group). At the beginning of
      intravitreal injection of ranibizumab, aqueous humor was collected and the
      concentration of VEGF was measured using ELISA. The concentration was compared
      between the two groups. RESULTS: Complete PVD was observed in 13 (39 %) eyes. The
      mean concentration of VEGF was 58 pg/ml in the PVD group and 91 pg/ml in the
      without PVD group. Multiple regression analysis revealed that the concentration
      of VEGF was significantly lower in the eyes with PVD than in those without PVD
      independent of age and sex (P = 0.02). CONCLUSIONS: Complete PVD is related to
      the lower concentration of aqueous VEDF in AMD eyes.

PMID- 25863677
TI  - Incontinence in children with treated attention-deficit/hyperactivity disorder.
AB  - INTRODUCTION: Attention-deficit/hyperactivity disorder (ADHD) and incontinence
      (nocturnal enuresis, daytime urinary incontinence and fecal incontinence) are
      common disorders in childhood. Both disorders are strongly associated with each
      other. OBJECTIVE: ADHD can affect compliance to incontinence therapy in a
      negative way; it can also affect outcome. The aim of the present study was to
      assess the prevalence of incontinence, age of bladder and bowel control, and
      psychological symptoms in children having treatment for ADHD compared to a
      control group. STUDY DESIGN: Forty children having treatment for ADHD (75% boys,
      mean age 11.4 years) and 43 matched controls (60.5% boys, mean age 10.7 years)
      were assessed. Their parents filled out questionnaires to assess: child
      psychopathology (Child Behavior Checklist), incontinence (Parental Questionnaire:
      Enuresis/Urinary Incontinence; Encopresis Questionnaire - Screening Version) and
      symptoms of the lower urinary tract (International-Consultation-on-Incontinence
      Questionnaire - Pediatric Lower Urinary Tract Symptoms). The ICD-10 diagnoses and
      children's IQ were measured by standardized instruments (Kinder-DIPS, Coloured
      Progressive Matrices/Standard Progressive Matrices). RESULTS: Rates of
      incontinence in the ADHD group (5% nocturnal enuresis, 5% daytime urinary
      incontinence, 2.5% fecal incontinence) did not differ significantly from
      incontinence rates in the control group (4.7% daytime urinary incontinence). More
      children in the ADHD group had Child Behavior Checklist scores in the clinical
      range. Further ICD-10 disorders were present in eight children with ADHD and in
      one control child. More children with ADHD had delayed daytime and nighttime
      bladder control, as well as delayed bowel control, than the controls. DISCUSSION:
      The present study showed that if children are treated for their ADHD, according
      to standard practice guidelines, incontinence rates are similar to those without
      ADHD. More children with ADHD reached continence at a later age than the
      controls, which could be an indicator of maturational deficits in the central
      nervous system. Additionally, children with ADHD showed higher rates of
      clinically relevant psychological symptoms. CONCLUSION: This study provides
      further information of the association between ADHD and incontinence. Treatment
      of ADHD may be associated with positive effects on incontinence outcomes.
      Therefore, children with ADHD should always be screened for incontinence problems
      and children with incontinence problems should also be screened for ADHD if
      symptoms of hyperactivity, inattention and/or impulsivity are also present.

PMID- 25863678
TI  - Commentary to "Effect of Botox injection at the bladder neck in boys with bladder
      dysfunction after valve ablation".

PMID- 25863679
TI  - Evidence for cholesterol-lowering activity by Bifidobacterium bifidum PRL2010
      through gut microbiota modulation.
AB  - Bifidobacteria are members of the human gut microbiota, which are known to
      influence the metabolic abilities of their host. Here, we investigated the
      capabilities of bifidobacteria to reduce cholesterol levels in synthetic growth
      media, clearly demonstrating assimilation of this molecule by particular
      bifidobacterial strains, including Bifidobacterium bifidum PRL2010 (LMG S-28692).
      The transcriptomic analysis of PRL2010 cells cultivated in the presence of
      cholesterol revealed a significantly increased transcription level of genes
      encoding putative transporters and reductases, indicative of specific mechanisms
      for cholesterol assimilation as well as cholesterol conversion to coprostanol.
      Cholesterol lowering activity of B. bifidum PRL2010 cells was further evaluated
      by means of an in vivo murine model, showing that the fecal microbiota of mice is
      modified toward those bacteria involved in the metabolism of cholesterol.

PMID- 25863680
TI  - Comparing Preoperative Targets to Failure-to-Rescue for Surgical Mortality
      Improvement.
AB  - BACKGROUND: Failure-to-rescue (FTR or death after postoperative complication) is
      thought to explain surgical mortality excesses across hospitals, and FTR is an
      emerging performance measure and target for quality improvement. We compared the
      FTR population to preoperatively identifiable subpopulations for their potential
      to close the mortality gap between lowest- and highest-mortality hospitals. STUDY
      DESIGN: Patients undergoing small bowel resection, pancreatectomy, colorectal
      resection, open abdominal aortic aneurysm repair, lower extremity arterial
      bypass, and nephrectomy were identified in the 2007 to 2011 Nationwide Inpatient
      Sample. Lowest- and highest-mortality hospitals were defined using risk- and
      reliability-adjusted mortality quintiles. Five target subpopulations were
      established a priori: the FTR population, predicted high-mortality risk
      (predicted highest-risk quintile), emergency surgery, elderly (>75 years old),
      and diabetic patients. RESULTS: Across the lowest mortality quintile (n=282
      hospitals, 56,893 patients) and highest-mortality quintile (282 hospitals, 45,784
      patients), respectively, the size of target subpopulations varied only for the
      FTR population (20.2% vs 22.4%, p=0.002) but not for other subpopulations.
      Variation in mortality rates across lowest- and highest-mortality hospitals was
      greatest for the high-mortality risk (7.5% vs 20.2%, p<0.0001) and FTR
      subpopulations (7.8% vs 18.9%, p<0.0001). The FTR and high-risk populations had
      comparable sensitivity (81% and 75%) and positive predictive value (19% and 20%,
      respectively) for mortality. In Monte Carlo simulations, the mortality gap
      between the lowest- and highest-mortality hospitals was reduced by nearly 75%
      when targeting the FTR population or the high-risk population, 78% for the
      emergency surgery population, but less for elderly (51%) and diabetic (17%)
      populations. CONCLUSIONS: Preoperatively identifiable patients with high
      estimated mortality risk may be preferable to the FTR population as a target for
      surgical mortality reduction.

PMID- 25863681
TI  - Obesity has no effect on outcomes following unicompartmental knee arthroplasty.
AB  - PURPOSE: Although obesity has historically been described as a contraindication
      to UKA, improved outcomes with modern UKA implant designs have challenged this
      perception. The purpose of this study was to assess the influence of obesity on
      the outcomes of UKA with a robotic-assisted system at a minimum follow-up of 24
      months with the hypothesis that obesity has no effect on robotic-assisted UKA
      outcomes. METHODS: There were 746 medial robotic-assisted UKAs (672 patients)
      with a mean age of 64 years (SD 11) and a mean follow-up time of 34.6 months (SD
      7.8). Mean overall body mass index (BMI) was 32.1 kg/m2 (SD 6.5), and patients
      were stratified into seven weight categories according to the World Health
      Organization classification. RESULTS: Patient BMI did not influence the rate of
      revision surgery to TKA (5.8 %) or conversion from InLay to OnLay design (1.7 %,
      n.s.). Mean postoperative Oxford knee score was 37 (SD 11) without correlation
      with BMI (n.s.). The type of prosthesis (InLay/OnLay) regardless of BMI had no
      influence on revision rate (n.s.). BMI did not influence 90-day readmissions (4.4
      %, n.s.), but showed significant correlation with higher opioid medication
      requirements and a higher number of physical therapy session needed to reach
      discharge goals (p = 0.031). CONCLUSION: These findings suggest that BMI does not
      influence clinical outcomes and readmission rates of robotic-assisted UKA at mid
      term. The classic contraindication of BMI >30 kg/m2 may not be justified with the
      use of modern UKA designs or techniques. LEVEL OF EVIDENCE: IV.

PMID- 25863683
TI  - Erratum to: Double Bond Stereochemistry Influences the Susceptibility of Short
      Chain Isoprenoids and Polyprenols to Decomposition by Thermo-Oxidation.

PMID- 25863682
TI  - Three-dimensional models of natural environments and the mapping of navigational
      information.
AB  - Much evidence has accumulated in recent years, demonstrating that the degree to
      which navigating insects rely on path integration or landmark guidance when
      displaced depends on the navigational information content of their specific
      habitat. There is thus a need to quantify this information content. Here we
      present one way of achieving this by constructing 3D models of natural
      environments using a laser scanner and purely camera-based methods that allow us
      to render panoramic views at any location. We provide (1) ground-truthing of such
      reconstructed views against panoramic images recorded at the same locations; (2)
      evidence of their potential to map the navigational information content of
      natural habitats; (3) methods to register these models with GPS or with stereo
      camera recordings and (4) examples of their use in reconstructing the visual
      information available to walking and flying insects. We discuss the current
      limitations of 3D modelling, including the lack of spectral and polarisation
      information, but also the opportunities such models offer to map the navigational
      information content of natural habitats and to test visual navigation algorithms
      under 'real-life' conditions. 

PMID- 25863684
TI  - Decreased expression of microRNA-125a-3p upregulates interleukin-23 receptor in
      patients with Hashimoto's thyroiditis.
AB  - Interleukin IL-23 receptor (IL-23R) is increasingly recognized as a key
      checkpoint in autoimmune diseases, including Hashimoto's thyroiditis (HT).
      However, the molecular mechanisms regulating IL-23R expression are still unknown.
      MicroRNAs have emerged as key regulators of various biological events via
      suppressing target mRNAs at the posttranscriptional level. In this study, we
      found that the IL-23R mRNA expression was increased in peripheral blood
      mononuclear cells from HT patients, and there was a positive correlation between
      the level of IL-23R mRNA and the serum level of anti-thyroglobulin antibody
      (TgAb). The miR-125a-3p expression was decreased and inversely correlated with
      elevated level of IL-23R in patients with HT. MiR-125a-3p inhibited IL-23R
      expression through directly targeting 3'untranslated region of IL-23R. An inverse
      correlation was observed between the level of miR-125a-3p and serum level of
      TgAb. Furthermore, we also found upregulated IL-23R expression and downregulated
      miR-125a-3p expression in thyroid tissues from HT patients. Taken together, our
      results indicate that decreased expression of miR-125a-3p was involved in the
      pathogenesis of Hashimoto's thyroiditis.

PMID- 25863685
TI  - QUAlity of Life Assessment in Spina bifida for Adults (QUALAS-A): development and
      international validation of a novel health-related quality of life instrument.
AB  - PURPOSE: Health-related quality of life (HRQOL) is important in spina bifida (SB)
      management. No clinically useful, comprehensive instrument incorporating
      bladder/bowel domains exists. We aimed to develop and validate a self-reported
      QUAlity of Life Assessment in Spina bifida for Adults (QUALAS-A). METHODS: We
      drafted the 53-question pilot instrument using a comprehensive item
      generation/refinement process. It was administered to an international
      convenience sample of adults with SB and controls recruited online via social
      media and in person at outpatient SB clinics (January 2013-September 2014). Final
      questions were determined by: clinical relevance, high factor loadings and domain
      psychometrics in an Internal Validation Sample randomly selected from United
      States participants (n = 250). External validity was evaluated in United States
      and International External Validation Samples (n = 165 and n = 117,
      respectively). Adults with SB completed the validated general WHOQOL-BREF and
      International Consultation on Incontinence Questionnaire (ICIQ). RESULTS: Mean
      age of 532 participants was 32 years (32.7 % males, 85.0 % Caucasian), similar to
      116 controls (p >= 0.08). There were 474 online and 58 clinical participants
      (61.1 % eligible). Face validity and content validity of the 3-domain, 15
      question QUALAS-A were established by patients, families and experts. Internal
      consistency and test-retest reliability were high for all domains (Cronbach's
      alpha >= 0.70, ICC >= 0.77). Correlations between QUALAS-A and WHOQOL-BREF were
      low (r <= 0.60), except for high correlations with Health and Relationships
      domain (0.63 <= r <= 0.71). Bladder and Bowel domain had a high correlation with
      ICIQ (r = -0.70). QUALAS-A scores were lower among adults with SB than without (p
      < 0.0001). QUALAS-A had good statistical properties in both External Validation
      Samples (Cronbach's alpha 0.68-0.77). CONCLUSIONS: QUALAS-A is a short, valid
      HRQOL tool for adults with SB.

PMID- 25863686
TI  - Use of indocyanine green alone for sentinel node biopsy in breast cancer.

PMID- 25863687
TI  - Computed tomography for non-traumatic headache in the emergency department and
      the impact of follow-up testing on altering the initial diagnosis.
AB  - The purpose of this study was twofold: (1) to determine the incidence of positive
      computed tomography (CT) findings in patients presenting to the emergency
      department (ED) with non-traumatic headache at our institution and (2) to examine
      follow-up exams, including lumbar puncture, non-enhanced CT, CT angiogram, CT
      venogram, and magnetic resonance imaging (MRI), to see how often the use of
      further testing changes the diagnosis. With IRB approval, 865 patients were
      identified through ED requisitions for CT head with the indication of headache
      during the calendar year 2011. Exclusion criteria included head trauma, prior
      intracranial surgery, focal neurologic symptoms, and known intracranial mass. CT
      results were divided into three categories: P0, P1, and P2. Negative studies were
      graded as P0. Positive studies were subdivided into clinically insignificant or
      P1 and clinically significant or P2. Clinically significant was defined as
      requiring medical treatment. Subsequently, the electronic medical records and
      picture archiving and communication system (PACS) were reviewed to determine the
      incidence of follow-up exams, including lumbar puncture or imaging. The secondary
      tests were divided into the same P0, P1, and P2 categories. There were 254
      positive studies: P1 clinically insignificant (27.1 %, 235/865) and P2 clinically
      significant (2.2 %, 19/865). Of 257 follow-up exams performed, the majority were
      lumbar punctures (36.0 %) or CT angiograms (29.5 %). In 19/257 exams or 7.4 %,
      the additional testing changed the clinically insignificant (P0/P1) diagnosis to
      a significant (P2) result. At our institution, there was a 2.2 % incidence of
      significant positive CT findings in patients presenting to the ED with non
      traumatic headache. Follow-up testing was variable and resulted in a 7.4 %
      increase in the severity of diagnosis compared to the initial negative CT scan. 

PMID- 25863688
TI  - Community knowledge, awareness and preventive practices regarding dengue fever in
      Puducherry - South India.
AB  - OBJECTIVES: To ascertain the knowledge, attitudes and practices of adult
      population in Puducherry, India, regarding Dengue Fever (DF). STUDY DESIGN: A
      cross-sectional survey was carried out to assess the Knowledge, Awareness and
      Preventive practices (KAP) among a selected community in Puducherry on DF,
      following a major dengue outbreak in 2012. METHODS: Between October 2012 &
      February 2013, an epidemiological survey was conducted among 400 households (HHs)
      from the most affected areas during dengue outbreak, which came under eight
      health delivery jurisdictions i.e. Primary Health Centres (PHCs) in Puducherry.
      Knowledge of dengue and the use of preventive measures were assessed by means of
      a pre-tested structured questionnaire. Logistic regression analysis was done to
      examine the association between different levels of education and income status
      with the knowledge of DF. The DF knowledge map was created based on the results
      achieved through the questionnaire using Arc GIS 10.2 software. RESULTS: Although
      about 86% of the participants had heard of dengue, although there was no adequate
      knowledge on dengue vector breeding habitat as 68% of the respondents thought
      drains & garbage as breeding places of dengue vectors. Only 25% of participants
      were aware of clean water as a breeding habitat. Insufficient knowledge of
      disease symptoms was found, with fever (59%) being the most common symptom.
      CONCLUSIONS: There is a lack of in-depth knowledge on dengue epidemiology in the
      Puducherry community and observation revealed that more needs to be done by the
      Government as well as community members to prevent vector mosquito breeding.

PMID- 25863689
TI  - A theoretical study on the strength of the C-NO2 bond and ring strain upon the
      formation of the intermolecular H-bonding interaction between HF and nitro group
      in nitrocyclopropane, nitrocyclobutane, nitrocyclopentane or nitrocyclohexane.
AB  - As a follow-up to our investigation into the influence of H-bond on the C-NO2
      trigger bond, a comparison of the effect of the H-bond on the ring strain energy
      with the C-NO2 bond dissociation energy was carried out in the HF complex with
      nitrocyclopropane, nitrocyclobutane, nitrocyclopentane, and nitrocyclohexane by
      using the DFT-B3LYP and MP2 (full) methods with the 6-311++G(2df,2p) and aug-cc
      pVTZ basis sets. The C-NO2 bond length decreases with strengthening of trigger
      bond while the ring perimeter increases companied by weakening of ring strain
      upon the complex formation. The H-bonding energy correlates well with the
      increment of ring perimeter and the change of ring bond angle. For
      nitrocyclopropane???HF, the effect of H-bond on the ring strain energy is
      notable, while for the other complex, it is negligible. Therefore, for
      nitrocyclopropane???HF, the origin of the change of explosive sensitivity might
      be due to the increment of the C-NO2 bond dissociation energy and decrease of the
      ring strain energy, while for the other complex, it might be only due to the
      strengthening of C-NO2 bond. The analysis of electron density shifts shows that
      the C-C bond in ring loses density while the C-NO2 bond gains density, leading to
      the weakened ring strain and strengthened C-NO2 bond, and thus the possibly
      reduced explosive sensitivity. 

PMID- 25863690
TI  - In-silico analysis of the structure and binding site features of an alpha
      expansin protein from mountain papaya fruit (VpEXPA2), through molecular
      modeling, docking, and dynamics simulation studies.
AB  - Fruit softening is associated to cell wall modifications produced by a set of
      hydrolytic enzymes and proteins. Expansins are proteins with no catalytic
      activity, which have been associated with several processes during plant growth
      and development. A role for expansins has been proposed during softening of
      fruits, and many fruit-specific expansins have been identified in a variety of
      species. A 3D model for VpEXPA2, an alpha-expansin involved in softening of
      Vasconcellea pubescens fruit, was built for the first time by comparative
      modeling strategy. The model was validated and refined by molecular dynamics
      simulation. The VpEXPA2 model shows a cellulose binding domain with a beta
      sandwich structure, and a catalytic domain with a similar structure to the
      catalytic core of endoglucanase V (EGV) from Humicola insolens, formed by six
      beta-strands with interconnected loops. VpEXPA2 protein contains essential
      structural moieties related to the catalytic mechanism of EGV, such as the
      conserved HFD motif. Nevertheless, changes in the catalytic environment are
      observed in the protein model, influencing its mode of action. The lack of
      catalytic activity of this expansin and its preference for cellulose are
      discussed in light of the structural information obtained from the VpEXPA2
      protein model, regarding the distance between critical amino acid residues.
      Finally, the VpEXPA2 model improves our understanding on the mechanism of action
      of alpha-expansins on plant cell walls during softening of V. pubescens fruit. 

PMID- 25863691
TI  - Recording and assessment of evoked potentials with electrode arrays.
AB  - In order to optimize procedure for the assessment of evoked potentials and to
      provide visualization of the flow of action potentials along the motor systems,
      we introduced array electrodes for stimulation and recording and developed
      software for the analysis of the recordings. The system uses a stimulator
      connected to an electrode array for the generation of evoked potentials, an
      electrode array connected to the amplifier, A/D converter and computer for the
      recording of evoked potentials, and a dedicated software application. The method
      has been tested for the assessment of the H-reflex on the triceps surae muscle in
      six healthy humans. The electrode array with 16 pads was positioned over the
      posterior aspect of the thigh, while the recording electrode array with 16 pads
      was positioned over the triceps surae muscle. The stimulator activated all the
      pads of the stimulation electrode array asynchronously, while the signals were
      recorded continuously at all the recording sites. The results are topography maps
      (spatial distribution of evoked potentials) and matrices (spatial visualization
      of nerve excitability). The software allows the automatic selection of the lowest
      stimulation intensity to achieve maximal H-reflex amplitude and selection of the
      recording/stimulation pads according to predefined criteria. The analysis of
      results shows that the method provides rich information compared with the
      conventional recording of the H-reflex with regard the spatial distribution. 

PMID- 25863692
TI  - Influence of head mass on temporo-parietal skull impact using finite element
      modeling.
AB  - The effect of head mass on its biomechanical response during lateral impact to
      the head is investigated in this computational study. The mass of the head of a
      state-of-the-art validated finite element head model is altered by +/- 10 % from
      the base value of 4.7 kg. Numerical simulations of lateral head impacts for 30
      cases (representing 15 human cadaver experiments * 2 mass configurations) are
      performed using the LS-DYNA solver at different velocities ranging from 2.4 to
      6.5 m/s and three impacting conditions representing different stiffness and
      shapes of the contact/impact surfaces. Results are compared with the original
      model using the baseline head mass, thus resulting in a total of 45 simulations.
      Present findings show that the head mass has greater influence for peak
      interaction forces and the force has a greater dependency on stiffness of contact
      surface than the shape. Mass variations have also influence on skull strain
      energy. Regardless of increase/decrease in skull strain energy influenced by head
      mass variations used in the computational study, the 50 % fracture tolerance
      limit was unaltered, which was 544 mJ. The present study gives a better
      understanding of the mechanism of temporo-parietal skull impact.

PMID- 25863693
TI  - Modeling the effect of dendritic input location on MEG and EEG source dipoles.
AB  - The cerebral sources of magneto- and electroencephalography (MEG, EEG) signals
      can be represented by current dipoles. We used computational modeling of
      realistically shaped passive-membrane dendritic trees of pyramidal cells from the
      human cerebral cortex to examine how the spatial distribution of the synaptic
      inputs affects the current dipole. The magnitude of the total dipole moment
      vector was found to be proportional to the vertical location of the synaptic
      input. The dipole moment had opposite directions for inputs above and below a
      reversal point located near the soma. Inclusion of shunting-type inhibition
      either suppressed or enhanced the current dipole, depending on whether the
      excitatory and inhibitory synapses were on the same or opposite side of the
      reversal point. Relating the properties of the macroscopic current dipoles to
      dendritic current distributions can help to provide means for interpreting MEG
      and EEG data in terms of synaptic connection patterns within cortical areas. 

PMID- 25863694
TI  - Exploration of EEG features of Alzheimer's disease using continuous wavelet
      transform.
AB  - We have developed a novel approach to elucidate several discriminating EEG
      features of Alzheimer's disease. The approach is based on the use of a variety of
      continuous wavelet transforms, pairwise statistical tests with multiple
      comparison correction, and several decision tree algorithms, in order to choose
      the most prominent EEG features from a single sensor. A pilot study was conducted
      to record EEG signals from Alzheimer's disease (AD) patients and healthy age
      matched control (CTL) subjects using a single dry electrode device during several
      eyes-closed (EC) and eyes-open (EO) resting conditions. We computed the power
      spectrum distribution properties and wavelet and sample entropy of the wavelet
      coefficients time series at scale ranges approximately corresponding to the major
      brain frequency bands. A predictive index was developed using the results from
      statistical tests and decision tree algorithms to identify the most reliable
      significant features of the AD patients when compared to healthy controls. The
      three most dominant features were identified as larger absolute mean power and
      larger standard deviation of the wavelet scales corresponding to 4-8 Hz (theta)
      during EO and lower wavelet entropy of the wavelet scales corresponding to 8-12
      Hz (alpha) during EC, respectively. The fourth reliable set of distinguishing
      features of AD patients was lower relative power of the wavelet scales
      corresponding to 12-30 Hz (beta) followed by lower skewness of the wavelet scales
      corresponding to 2-4 Hz (upper delta), both during EO. In general, the results
      indicate slowing and lower complexity of EEG signal in AD patients using a very
      easy-to-use and convenient single dry electrode device.

PMID- 25863695
TI  - Preeclampsia in autologous and oocyte donation pregnancy: is there a different
      pathophysiology?
AB  - Oocyte donation (OD) is a specific method of artificial reproductive technology
      that is accompanied by a higher risk of preeclampsia during pregnancy. The
      pathophysiological mechanism underlying preeclampsia in OD pregnancies is thought
      to differ from preeclampsia in autologous pregnancies. As preeclampsia in
      autologous pregnancies is suggested to be associated with complement activation,
      we studied C4d deposition, circulating complement components and placental
      complement regulatory proteins in preeclamptic OD pregnancies. Women with
      uncomplicated and preeclamptic pregnancies after OD or spontaneous conception
      were selected. We stained the placentas for C4d, marker for complement
      activation, measured complement factors C1q, C3 and C4 in maternal sera and
      quantified the placental mRNA expression of complement regulatory proteins CD46,
      CD55 and CD59. A significantly (p < 0.03) higher incidence of C4d deposition was
      observed in placentas from women with preeclampsia compared with uncomplicated
      pregnancies, both OD and autologous. The level of complement factors in serum did
      not differ between the groups. Children born in the autologous preeclampsia group
      were significantly lower in birth weight (p < 10th percentile) compared with the
      preeclamptic OD group. In addition, the placental mRNA expression level of
      complement regulatory proteins was significantly lower in uncomplicated and
      preeclamptic OD compared with the autologous pregnancies. In line with autologous
      preeclampsia pregnancies, there is excessive activation of complement in
      preeclamptic OD pregnancies. However, in contrast to autologous pregnancies this
      is not associated with counterbalancing upregulation of complement regulatory
      proteins. Furthermore, C4d deposition in OD pregnancies is not related to the
      severity of preeclampsia, suggesting another trigger or regulatory mechanism of
      placental C4d deposition in preeclamptic OD pregnancies.

PMID- 25863696
TI  - Underutilisation of Victorian in-patient palliative care consultation services?
      Results of an exploratory study.

PMID- 25863697
TI  - Determination of cocaine in Real banknotes circulating at the State of Rio de
      Janeiro, Brazil.
AB  - This paper shows the result of a study on the extent of cocaine contamination in
      Real banknotes in circulation in the state of Rio de Janeiro (Brazil). A study of
      the percentage of contaminated banknotes was made, as well as a study on the
      contamination of banknotes based on different values, and a study of
      contamination depending on the region where the banknote was collected. The idea
      of this last study was to verify if the peculiar characteristics of the region of
      study (in particular, the city of Rio de Janeiro) influence the amount of cocaine
      in the banknotes. Some regions have higher consumption/drug trafficking of
      cocaine than others. Also, some contaminated banknotes confiscated directly from
      drug dealers and users were analyzed. Also, is showed in this paper all the
      optimization of the available analytical techniques for making the measurements
      possible. 

PMID- 25863698
TI  - The impact of age at death on the lag time of radiocarbon values in human bone.
AB  - Analysis of modern bomb-pulse radiocarbon in human bone offers data needed to
      interpret the post-mortem interval in skeletonized human remains recovered from
      forensic contexts. Radiocarbon analysis of different tissues with distinct rates
      of remodeling allows proper placement of the values on the modern bomb-curve.
      However, the lag time between the date of intercept on the curve and the actual
      death date is largely affected by the age at death. Published data on radiocarbon
      analysis of individuals of known age at death and death dates indicate that this
      lag time increases with age until about 60 years. The lag time documented for
      each decade of life can be used to compensate for this age-related factor and
      increase the accuracy of interpretation of the death date. While this method
      could be greatly improved by original research with a larger sample size, this
      study provides an adequate point from which to launch further investigations into
      the subject. 

PMID- 25863699
TI  - Raman spectroscopy of uranium compounds and the use of multivariate analysis for
      visualization and classification.
AB  - Raman spectroscopy was used on 95 samples comprising mainly of uranium ore
      concentrates as well as some UF4 and UO2 samples, in order to classify uranium
      compounds for nuclear forensic purposes, for the first time. This technique was
      selected as it is non-destructive and rapid. The spectra obtained from 9
      different classes of chemical compounds were subjected to multivariate data
      analysis such as principal component analysis (PCA), partial least square
      discriminant analysis (PLS-DA) and Fisher Discriminant Analysis (FDA). These
      classes were ammonium diuranate (ADU), sodium diuranate (SDU), ammonium uranyl
      carbonate (AUC), uranyl hydroxide (UH), UO2, UO3, UO4, U3O8 and UF4. Unsupervised
      PCA of full spectra shows fairly good distinction among the classes with some
      overlaps observed with ADU and UH. These overlaps are also reflected in the
      poorer specificities determined by PLS-DA. Higher values of sensitivities and
      specificities of remaining compounds were obtained. Supervised FDA based on
      reduced dataset of only 40 variables shows similar results to that of PCA but
      with closer clustering of ADU, UH, SDU, AUC. As a rapid and non-destructive
      technique, Raman spectroscopy is useful and complements existing techniques in
      multi-faceted nuclear forensics. 

PMID- 25863700
TI  - Microbial degradation of gasoline in soil: Effect of season of sampling.
AB  - In cases where fire debris contains soil, microorganisms can rapidly and
      irreversibly alter the chemical composition of any ignitable liquid residue that
      may be present. In this study, differences in microbial degradation due to the
      season in which the sample is collected was examined. Soil samples were collected
      from the same site during Fall, Winter, Spring and Summer and the degradation of
      gasoline was monitored over 30 days. Predominant viable bacterial populations
      enumerated using real-time PCR and reverse transcriptase polymerase chain
      reaction (RT-PCR) enumeration revealed the predominant viable bacterial genera to
      be Alcaligenes, Bacillus, and Flavobacterium. Overall, the compounds most
      vulnerable to microbial degradation are the n-alkanes, followed by the mono
      substituted alkylbenzenes (e.g., toluene, ethylbenzene, propylbenzene and
      isopropylbenzene). Benzaldehyde (a degradation product of toluene) was also
      identified as a marker for the extent of biodegradation. Ultimately, it was
      determined that soil collected during an unusually hot and dry summer exhibited
      the least degradation with little to no change in gasoline for up to 4 days,
      readily detectable n-alkanes for up to 7 days and relatively high levels of
      resilient compounds such as o-xylene, p-xylene and 1,3,5-trimethylbenzene. These
      results demonstrate, however, that prompt preservation and/or analysis of soil
      evidence is required in order to properly classify an ignitable liquid residue. 

PMID- 25863701
TI  - UV-vis spectrophotometric determination of trinitrotoluene (TNT) with
      trioctylmethylammonium chloride as ion pair assisted and disperser agent after
      dispersive liquid-liquid microextraction.
AB  - In the present study, a simple, fast and inexpensive method based on dispersive
      liquid-liquid microextraction (DLLME) prior to microvolume UV-vis
      spectrophotometry was developed for the preconcentration and determination of
      trinitrotoluene (TNT). The procedure is based on the color reaction of TNT in
      alkaline medium and extraction into CCl4 as an ion pair assisted by
      trioctylmethylammonium chloride, which also acts as a disperser agent.
      Experimental parameters affecting the DLLME method such as pH, concentration of
      sodium hydroxide, amount of trioctylmethylammonium chloride, type and volume of
      extraction solvent were investigated and optimized. Under the optimum conditions,
      the limit of detection (LOD) was 0.9ng/mL and the calibration curve was linear in
      the range of 3-200ng/mL. The relative standard deviation for 25 and 100ng/mL of
      TNT were 3.7% and 1.5% (n=6), respectively. The developed DLLME method was
      applied for the determination of TNT in different water and soil samples. 

PMID- 25863702
TI  - An assessment of the subjectivity of sperm scoring.
AB  - Current histological investigation of vaginal swabs after alleged sexual assault
      includes the scoring of spermatozoa (0, + to ++++) and the recording of visible
      tails. It is a method that is universally employed. Despite this method being
      used for 40 years, there has never been a study investigating its suitability for
      forensic science. Here, we investigate the reproducibility and subjectivity of
      sperm scoring among different investigators. Dilutions of seminal fluid were
      randomly distributed onto 20 slides, stained with haematoxylin/eosin and assessed
      by 37 investigators, over 2 years. Slides were assessed for levels of spermatozoa
      and the presence of tails. Each slide was scored by a minimum of 25
      investigators. On no slide was there a consensus between all scores. Standard
      deviation remained below 1, but relative standard deviation (RSD) ranged from 6
      to 105% in a positive correlation as the average score decreased. Spermatozoa
      were not observed 56 times (9.6%) and 27 investigators (73%) did not observe
      spermatozoa on at least one slide. Spermatozoa with tails were observed on every
      slide by at least 10 examiners, but as the average score of the slide decreased,
      so did the observation of tails. The current sperm scoring method is highly
      subjective with a particularly high %RSD in slides with low overall sperm counts.
      Moreover, the recording of tails does not add value to the current technique of
      sperm scoring. Further research might improve the objectivity of sperm scoring
      and the reliability of recording of tails. 

PMID- 25863703
TI  - Body weight status and onset of functional limitations in U.S. middle-aged and
      older adults.
AB  - BACKGROUND: The sweeping obesity epidemic could further increase the incidence of
      functional limitations in the U.S. rapidly aging population. OBJECTIVE: To
      examine the relationship between body weight status and onset of functional
      limitations in U.S. middle-aged and older adults. METHODS: Study sample came from
      1992 to 2010 waves of the Health and Retirement Study, a nationally
      representative longitudinal survey of community-dwelling middle-aged and older
      adults. Body mass index (BMI) was calculated from self-reported height/weight.
      Functional limitations were classified into physical mobility limitation (PM),
      large muscle function limitation (LMF), activities of daily living limitation
      (ADL), gross motor function limitation (GMF), and fine motor function limitation
      (FMF). Mixed-effect logistic regressions were performed to estimate the
      relationship between prior-wave body weight status and current-wave onset of
      functional limitations, adjusted for individual characteristics and survey
      design. RESULTS: Prior-wave body weight status prospectively predicted onset of
      functional limitation, and the relationship showed a U-shaped pattern. Compared
      with their normal weight counterparts, the odds ratios (ORs) in underweight (BMI
      < 18.5) and obese (BMI >= 30) adults were 1.30 (95% confidence interval, 1.05
      1.62) and 2.31 (2.11-2.52) for PM, 1.20 (0.96-1.50) and 1.63 (1.49-1.79) for LMF,
      2.02 (1.66-2.46) and 1.40 (1.28-1.54) for ADL, 1.96 (1.60-2.39) and 1.77 (1.62
      1.93) for GMF, and 1.66 (1.37-2.02) and 1.34 (1.22-1.46) for FMF, respectively.
      For PM, LMF and GMF, the impact of obesity appeared more pronounced in women,
      whereas that of underweight more pronounced in men. CONCLUSIONS: Proper weight
      management during aging is crucial in preventing functional limitations in middle
      aged and older adults.

PMID- 25863704
TI  - Ongoing evaluation of video-based assessment of proctors' scoring of the
      fundamentals of laparoscopic surgery manual skills examination.
AB  - BACKGROUND: In continued efforts to maintain standards required for high-stakes
      examination administration, Society of American Gastrointestinal and Endoscopic
      Surgeons' Fundamentals of Laparoscopic Surgery (FLS) program requires all
      prospective test proctors to complete the New FLS Proctor Workshop. As the FLS
      proctor pool and training evolves, the influence of experience on performance is
      not clear. In the previous work, we proposed that asynchronous web-based
      performances might be used to train proctors. In this study, we assessed the
      accuracy of proctors' ratings from asynchronous web-based performances by
      comparing the sensitivity and the specificity of ratings from proctors having
      varied experience levels. METHODS: A sample of 42 (26% of all registered
      proctors) FLS proctors (recently trained novice, n = 15; intermediate, n = 20;
      and expert, n = 7) viewed 2 videotaped, laparoscopic-view FLS performances via
      the web. The first performance (error) contained 1 predetermined critical
      performance error in each of the 5 tasks (5 total errors), whereas the second
      performance (no error) contained no critical errors. For both the performances,
      participants noted time to complete each of the 5 tasks and any critical errors
      they observed (dichotomously scored). Participants also completed a demographic
      section that captured years of experience as a proctor. Using the Kruskal-Wallis
      test, we compared new trainee, intermediate, and expert proctors' recorded task
      times for both the performances. The sensitivity and the specificity values were
      also independently calculated using ratings from the error and the no error
      performances and then compared using the same test. RESULTS: There were no
      differences in recorded times across proctor groups for any of the tasks; p =
      0.21 and 0.94. Rating sensitivity was 79% (novice), 75% (intermediate), and 83%
      (expert), with no significant differences across experience levels; p > 0.46.
      Following removal of the peg transfer task that had particularly low sensitivity,
      the sensitivity for the remaining 4 tasks increased [88% and 92%]. The
      specificity was 93% (novice), 86% (intermediate), and 100% (expert); p = 0.046.
      Comments from less-experienced proctors indicated that their focus on noncritical
      performance issues, such as "loop not on black line" and "air knot," were
      consistent with decreased specificity. CONCLUSIONS: Favorable results of this
      pilot study suggest that web-based FLS performances may be used for assessing FLS
      proctors' rating quality with adequate sensitivity and specificity. Decreased
      rating specificity from intermediate proctors indicates that these proctors would
      benefit from increased testing frequencies, updated training on current FLS
      proctoring standards, and ongoing performance review.

PMID- 25863705
TI  - Maternal and paternal serum concentrations of perfluoroalkyl and polyfluoroalkyl
      substances and the secondary sex ratio.
AB  - Select persistent environmental chemicals have been associated with a reduction
      in the secondary sex ratio (SSR), or the ratio of male to female live births. We
      evaluated preconception maternal, paternal, and couple serum concentrations of
      perfluoroalkyl and polyfluoroalkyl substances (PFASs) in relation to the SSR,
      given the absence of previous investigation. Two hundred thirty-three couples
      from Michigan and Texas were enrolled prior to conception and prospectively
      followed through delivery of a singleton birth, 2005-2009. Maternal and paternal
      serum concentrations (ng mL(-1)) were measured at baseline for seven PFASs.
      Logistic regression models were used to estimate odds ratios (ORs) and 95%
      confidence intervals (CIs) for a male birth, after adjusting for potential
      confounders. When maternal and paternal PFAS concentrations were modeled jointly,
      five of the seven PFASs, including the two most prominent PFASs, perfluorooctane
      sulfonic acid and perfluorooctanoic acid, were not significantly associated with
      the SSR. However, paternal N-methyl-perfluorooctane sulfonamidoacetic acid
      (MeFOSAA) and perfluorononanoic acid (2nd versus 1st tertile, OR, 0.43, 95% CI,
      0.21-0.88) were significantly associated with an excess of female births.
      Meanwhile, a dose-response relation was observed only for paternal MeFOSAA (2nd
      versus 1st tertile, OR, 0.53, 95% CI, 0.26-1.10; 3rd versus 1st tertile, OR,
      0.34, 95% CI, 0.13-0.89). This study suggests a possible dose-response relation
      between a less prevalent PFAS and a reversal in the SSR, though the underlying
      mechanisms remain unknown and the findings await corroboration to eliminate other
      explanations including chance.

PMID- 25863706
TI  - Nasal soft-tissue and vault deviation in unicoronal synostosis.
AB  - BACKGROUND: Unicoronal synostosis (UCS) results in nasal root deviation toward
      the fused side of the face, resulting in an apparent nasal dorsal deviation to
      the non-fused side. The impact of the altered radix position on the
      osteocartilaginous vault and nasal soft tissue has not been analyzed. The purpose
      of this study is to morphometrically assess the nasal structure and deviation in
      UCS. We hypothesize the proximal etiology exerts an impact on the distal nasal
      form, compared to controls. METHODS: Demographic data were tabulated and computed
      tomographic information recorded. Three-dimensional reconstruction was created
      and analyzed digitally (using Surgi Case). Morphometric landmarks were determined
      and used to perform measurements on the nasal soft tissue and osseous skull
      surface to evaluate nasal deviation within a midsaggital plane (MSP). RESULTS:
      Forty three-dimensional CT scans of 20 UCS patients and 20 control subjects were
      analyzed. The deviation angle of the nose to the non-fused side was 6.6 +/- 2.9
      degrees  in the bony layer. In the soft-tissue layer, the deviation angle of the
      nasal dorsum line to the non-fused side was 5.4 +/- 3.4 degrees . The tip of the
      nose showed a significant deviation to the non-fused side (2.2 +/- 1.2 mm).
      Paired landmarks (alares, inferior lateral nostril bases) related to the MSP
      showed a greater distance on the non-fused side. Paired landmarks related to an
      intrinsic nasal midline (Nsup-ANS; tip-columella line (TCL)) did not show any
      significant differences. CONCLUSION: UCS confers osteocartilaginous and soft
      tissue nasal deviation, with the distal nose toward the non-fused side. The nasal
      root inclination underpins this asymmetry across the midsaggital reference plane.
      However, the nose in isolation exhibits balanced side-side proportions.

PMID- 25863707
TI  - Cervical spine surgery in ankylosing spondylitis: Review and current concept.
AB  - Ankylosing spondylitis of the cervical spine is associated with stiff kyphosis
      and increased risk of transversal unstable fracture. A spine surgeon may be
      involved mainly in the management of trauma cases, but in some situations,
      corrective surgery of a kyphotic cervical deformity is needed. Both types of
      cases carry specific aspects and rely on principles that differ from those
      associated with more common cervical surgery. This paper is a review of the
      literature regarding cervical surgery in cases of ankylosing spondylitis. It
      addresses practical technical questions. 

PMID- 25863708
TI  - [Pre-therapeutic: what could mean this term?].

PMID- 25863709
TI  - The effect of pre-adsorption of OVA or WPC on subsequent OVA or WPC fouling on
      heated stainless steel surface.
AB  - Fouling on the heat exchanger surface during food processing has been researched
      extensively due to its great importance in energy efficiency, product quality and
      food safety. The nature of heat exchanger surface has an effect on the initial
      deposition behavior and deposit removal behavior to some degree. Protein
      adsorption on surface is considered to be the initial stage in fouling. In the
      current study, protein 'pre-adsorption' at room temperature on stainless steel
      has been investigated as a means to influence the behavior of protein fouling at
      pasteurization temperatures. Pre-adsorption was carried out with whey protein
      concentrate (WPC) and ovalbumin (OVA), respectively, which reduced the fouling of
      OVA (~20-30% energy saving in the processing time examined). However, the pre
      adsorption had little effect on fouling of whey protein concentrate. Contact
      angles were measured to show the surface change due to protein pre-adsorption.
      Protein pre-adsorption made the surfaces more hydrophilic. 

PMID- 25863710
TI  - The antimicrobial peptide microcin J25 stabilizes the gel phase of bacterial
      model membranes.
AB  - The bacterial membrane interaction of the antimicrobial peptide microcin J25 was
      studied with the probe-free techniques Langmuir monolayers and infrared
      spectroscopy. Membrane model systems composed by
      phosphatidylethanolamine:phosphatidylglycerol 7:3, which mimic the cytoplasmic
      membrane of Gram negative bacteria, were used in both monolayer and bilayer
      approaches. The peptide reduced the transition surface pressure of the expanded
      to-condensed lipid monolayer states, as well as increased the gel-to-liquid
      crystalline transition temperature in bilayers, indicating a stabilization of
      membrane ordered state. In addition, a reduction of the surface pressure at which
      condensed domains appeared was observed upon mixed monolayers compression after
      microcin J25 adsorption. The results indicate a favorable interaction of microcin
      J25 with bacterial membrane model systems. Also, the effects on the ordered
      phases stabilization are discussed in terms of the biological effects observed in
      membranes of sensitive cells. 

PMID- 25863711
TI  - Lipase immobilization on epoxy-activated poly(vinyl acetate-acrylamide)
      microspheres.
AB  - Poly(vinyl acetate-acrylamide) microspheres with an average diameter of 2-4MUm
      were successfully prepared and characterized via SEM and FTIR. Then the
      microspheres were modified with epoxy groups through reacting with
      epichlorohydrin and used as carriers to covalently immobilize Candida rugosa
      lipase. The results revealed that agitation played an important role on epoxy
      activation and the immobilization ratio increased with the increase of the epoxy
      density. On the other hand, the specific activity of the immobilized lipase as
      well as the activity recovery declined gradually with the increase in the
      immobilization ratio from 72% to 93%, which were attributed to the steric
      hindrance effects caused by enzyme overloading. When epoxy density was 76MUmol/g
      microsphere, the activity recovery reached the maximum at 47.5%, and the activity
      of the immobilized lipase was 261.3U/g microsphere. Moreover, the thermal
      stability of the immobilized lipase was much better than that of the free one,
      which indicated potential applications of the immobilized lipase. 

PMID- 25863712
TI  - Sodium alginate-cross-linked polymyxin B sulphate-loaded solid lipid
      nanoparticles: Antibiotic resistance tests and HaCat and NIH/3T3 cell viability
      studies.
AB  - Polymyxins are a group of antibiotics with a common structure of a cyclic peptide
      with a long hydrophobic tail. Polymyxin B sulphate (PLX) has cationic charge,
      which is an obstacle for the efficient loading into Solid Lipid Nanoparticles
      (SLN). In the present paper, we describe an innovative method to load PLX into
      SLN to achieve the sustained release of the drug. PLX was firstly cross-linked
      with sodium alginate (SA) at different ratios (1:1, 1:2 and 1:3 SA/PLX), and
      loaded into SLN produced by high pressure homogenization (HPH). Optimized SLN
      were produced applying 500bar pressure and 5 homogenization cycles. The best
      results were obtained with SA/PLX (1:1), recording 99.08+/-1.2% for the
      association efficiency of the drug with SA, 0.99+/-10g for the loading capacity
      and 212.07+/-5.84% degree of swelling. The rheological profile of aqueous SA
      solution followed the typical behaviour of concentrated polymeric solutions,
      whereas aqueous SA/PLX solution exhibited a gel-like dynamic behaviour.
      Micrographs show that SA/PLX depicted a porous and discontinuous amorphous phase
      in different ratios. The encapsulation efficiency of SA/PLX (1:1) in SLN, the
      mean particle diameter, polydispersity index and zeta potential were,
      respectively, 82.7+/-5.5%; 439.5+/-20.42nm, 0.241+/-0.050 and -34.8+/-0.55mV. The
      effect of SLN on cell viability was checked in HaCat and NIH/3T3 cell lines, and
      the minimal inhibitory concentrations (MIC) were determined in Pseudomonas
      aeruginosa strains. SA/PLX-loaded SLN were shown to be less toxic than free PLX.
      Minimal inhibitory concentrations (MIC) showed the presence of the cross-linker
      polymer-drug complex, and SLN were shown to enhance MIC in the evaluated strains.

PMID- 25863713
TI  - In vitro controlled release of Rifampicin through liquid-crystalline folate
      nanoparticles.
AB  - Rifampicin is one of the frontline drugs for tuberculosis therapy but poor
      bioavailability of Rifampicin in combination with other anti-tuberculosis drugs
      is a subject of concern. Nano-based formulations for sustained release of anti
      tubercular drugs have been shown to increase antibacterial efficacy and
      pharmacokinetic behavior. In the present study, liquid-crystalline folate
      nanoparticles were designed for sustained delivery of Rifampicin and its in vitro
      release study is reported. Liquid-crystalline nanoparticles of biocompatible
      folate ions consist of self assembled structures, resulting in high
      encapsulation, controlled release and low drug losses of about 20-30%, which is
      significant in itself. This study reports the size-control method of forming
      Rifampicin encapsulated folate nanoparticles as well as the parameters to control
      the release profiles of Rifampicin through these nanoparticles. These designs are
      able to present sustained release for over 25 days. The effect of different
      parameters such as nanoparticles size, type of cross-linking cation, cross
      linking cation concentration and drug-loading on Rifampicin release was studied
      in vitro. The intracellular uptake and low cytotoxicity of nanoparticles by
      alveolar macrophages was also demonstrated using fluorescence microscopy and MTT
      assay respectively. 

PMID- 25863715
TI  - About Cognitive Outcome Measures at Ecological Signal-to-Noise Ratios and
      Cognitive-Driven Hearing Aid Signal Processing.
AB  - PURPOSE: The purpose of this article is to discuss 2 questions concerning how
      hearing aids interact with hearing and cognition: Can signal processing in
      hearing aids improve memory? Can attention be used for top-down control of
      hearing aids? METHOD: Memory recall of sentences, presented at 95% correct speech
      recognition, was assessed with and without binary mask noise reduction. A short
      literature review was performed on recent findings on new brain-imaging
      techniques showing potential for hearing aid control. CONCLUSIONS: Two
      experiments indicate that it is possible to show improved memory with an
      experimental noise reduction algorithm at ecological signal-to-noise ratios and
      that it is possible to replicate these findings in a new language. The literature
      indicates that attention-controlled hearing aids may be developed in the future.

PMID- 25863714
TI  - One day access to a running wheel reduces self-administration of D
      methamphetamine, MDMA and methylone.
AB  - BACKGROUND: Exercise influences drug craving and consumption in humans and drug
      self-administration in laboratory animals, but the effects can be variable.
      Improved understanding of how exercise affects drug intake or craving would
      enhance applications of exercise programs to human drug users attempting
      cessation. METHODS: Rats were trained in the intravenous self-administration
      (IVSA) of D-methamphetamine (METH; 0.05 mg/kg/inf), 3,4
      methylenedioxymethamphetamine (MDMA; 0.5 mg/kg/inf) or methylone (0.5 mg/kg/inf).
      Once IVSA was established, the effect of ~ 22 h of wheel access in the home cage
      on subsequent drug taking was assessed in a two cohort crossover design. RESULTS:
      Provision of home cage wheel access during the day prior to IVSA sessions
      significantly decreased the self-administration of METH, MDMA and methylone. At
      the individual level, there was no correlation between the amount a rat used the
      wheel and the size of the individual's decrease in drug intake. CONCLUSIONS:
      Wheel access can reduce self-administration of a variety of psychomotor
      stimulants. It does so immediately, i.e., without a need for weeks of exercise
      prior to drug access. This study therefore indicates that future mechanistic
      investigations should focus on acute effects of exercise. In sum, the results
      predict that exercise programs can be used to decrease stimulant drug use in
      individuals even with no exercise history and an established drug taking pattern.

PMID- 25863716
TI  - Oncolytic adenovirus research evolution: from cell-cycle checkpoints to immune
      checkpoints.
AB  - Oncolytic adenoviruses are modified to exploit the aberrant expression of
      proteins in cancer cells to obtain cancer-selective replication. Moreover, the
      natural tropism of oncolytic adenoviruses can be redirected to tumor cells.
      Clinical trials revealed that oncolytic viruses showed poor replication in the
      tumor that is due in part to the immune response against the virus. More recent
      data demonstrated that tumor infection might subvert the tumor immune system and
      lead to an anti-tumor immune response. In the next few years, combination of
      adenoviruses with immune checkpoint antibodies and other immune modulators will
      be tested in clinical trials. 

PMID- 25863717
TI  - MicroRNAs and oncolytic viruses.
AB  - MicroRNAs regulate gene expression in mammalian cells and often exhibit tissue
      specific expression patterns. Incorporation of microRNA target sequences can be
      used to control exogenous gene expression and viral tropism in specific tissues
      to enhance the therapeutic indices of oncolytic viruses expressing therapeutic
      transgenes. Continued development of this targeting strategy has resulted in the
      generation of unattenuated oncolytic viruses with enhanced potency, broad species
      tropisms and reduced off-target toxicities in multiple-tissues simultaneously.
      Furthermore, oncolytic viruses have been used to enhance the delivery, duration
      and therapeutic efficacy of microRNA-based therapeutics designed to either
      restore or inhibit the function of dysregulated microRNAs in cancer cells. Recent
      efforts focused on combining oncolytic virotherapy and microRNA regulation have
      generated increasingly potent and safe cancer therapeutics. 

PMID- 25863719
TI  - Investigation of some factors affecting on release of radon-222 from
      phosphogypsum waste associated with phosphate ore processing.
AB  - The aim of this study is oriented to investigate the influence of some
      physicochemical factors such as radium distribution, grain size, moisture content
      and chemical constituents on releases of radon-222 from the accumulated
      phosphogypsum (PG) waste. The emanation fraction, activity concentration in the
      pore and the surface exhalation rate of radon-222 in the bulk PG waste are 34.5
      +/- 0.3%, 238.6 +/- 7.8 kBq m(-3) and 213 +/- 6.9 mBq m(-2) s(-1), respectively.
      These values were varied and enhanced slightly in the fine grain sizes (F1 <
      0.125 mm) by a factor of 1.05 folds compared to the bulk residue. It was also
      found that release of radon from residue PG waste was controlled positively by
      radium (Ra-226), calcium (CaSO4) and strontium (SrO). About 67% of radon release
      attributed to the grain size below 0.5 mm, while 33% due to the large grain size
      above 0.5 mm. The emanation fraction of Rn-222 is increased with moisture content
      and the maximum emanation is ~43% of moisture of 3-8%. It reduced slowly with the
      continuous increase in moisture till 20%. Due to PG waste in situ can be
      enhancing the background to the surround workers and/or public. Therefore, the
      environmental negative impacts due to release of Rn-222 can be minimized by
      legislation to restrict its civil uses, or increasing its moisture to ~10%, or by
      the particle size separation of the fine fraction containing the high levels of
      Ra-226 followed by a suitable chemical treatment or disposal; whereas the low
      release amount can be diluted and used in cement industry, roads or dam
      construction. 

PMID- 25863720
TI  - Anthropogenic radionuclide fluxes and distribution in bottom sediments of the
      cooling basin of the Ignalina Nuclear Power Plant.
AB  - Based on gamma-ray emitting artificial radionuclide spectrometric measurements,
      an assessment of areal and vertical distribution of (137)Cs, (60)Co and (54)Mn
      activity concentrations in bottom sediments of Lake Druksiai was performed.
      Samples of bottom sediments from seven monitoring stations within the cooling
      basin were collected in 1988-1996 and 2007-2010 (in July-August). For
      radionuclide areal distribution analysis, samples from the surface 0-5 cm layer
      were used. Multi sample cores sliced 2 cm, 3 cm or 5 cm thick were used to study
      the vertical distribution of radionuclides. The lowest (137)Cs activity
      concentrations were obtained for two stations that were situated close to
      channels with radionuclide discharges, but with sediments that had a
      significantly smaller fraction of organic matter related to finest particles and
      consequently smaller radionuclide retention potential. The (137)Cs activity
      concentration was distributed quite evenly in the bottom sediments from other
      investigated monitoring stations. The highest (137)Cs activity concentrations in
      the bottom sediments of Lake Druksiai were measured in the period of 1988-1989;
      in 1990, the (137)Cs activity concentrations slightly decreased and they varied
      insignificantly over the investigation period. The obtained (238)Pu/(239,240)Pu
      activity ratio values in the bottom sediments of Lake Druksiai represented
      radioactive pollution with plutonium from nuclear weapon tests. Higher (60)Co and
      (54)Mn activity concentrations were observed in the monitoring stations that were
      close to the impact zones of the technical water outlet channel and industrial
      rain drainage system channel. (60)Co and (54)Mn activity concentrations in the
      bottom sediments of Lake Druksiai significantly decreased when operations at both
      INPP reactor units were stopped. The vertical distribution of radionuclides in
      bottom sediments revealed complicated sedimentation features, which may have been
      affected by a number of natural and anthropogenic factors resulting in mixing,
      resuspension and remobilization of sediments and radionuclides. The associated
      with particles (137)Cs flux was 129 Bq/(m(2) year). The (137)Cs transfer rate
      from water into bottom sediments was 14.3 year(-1) (or, the removal time was 25
      days). The Kd value for (137)Cs in situ estimated from trap material was 80
      m(3)/kg. The associated with particles (60)Co flux was 21 Bq/(m(2) year), when
      (60)Co activity concentration in sediment trap particles was 15.7 +/- 5 Bq/kg.
      (60)Co activity concentration in soluble form was less than the minimum
      detectable activity (MDA = 1.3 Bq/m(3)). Then, the conservatively derived Kd
      value for (60)Co was >90 m(3)/kg. 

PMID- 25863721
TI  - Quantifying the spatial and temporal variation in dose from external exposure to
      radiation: a new tool for use on free-ranging wildlife.
AB  - Inadequate dosimetry is often the fundamental problem in much of the
      controversial research dealing with radiation effects on free-ranging wildlife.
      Such research is difficult because of the need to measure dose from several
      potential pathways of exposure (i.e., internal contamination, external
      irradiation, and inhalation). Difficulties in quantifying external exposures can
      contribute significantly to the uncertainties of dose-effect relationships.
      Quantifying an animal's external exposure due to spatial-temporal use of habitats
      that can vary by orders of magnitude in radiation levels is particularly
      challenging. Historically, wildlife dosimetry studies have largely ignored or
      been unable to accurately quantify variability in external dose because of
      technological limitations. The difficulties of quantifying the temporal-spatial
      aspects of external irradiation prompted us to develop a new dosimetry instrument
      for field research. We merged two existing technologies [Global Positioning
      Systems (GPS) and electronic dosimeters] to accommodate the restrictive
      conditions of having a combined unit small enough to be unobtrusively worn on the
      neck of a free-ranging animal, and sufficiently robust to withstand harsh
      environmental conditions. The GPS-dosimeter quantifies the spatial and temporal
      variation in external dose as wildlife traverse radioactively contaminated
      habitats and sends, via satellites, an animal's location and short term
      integrated dose to the researcher at a user-defined interval. Herein we describe:
      (1) the GPS-dosimeters; (2) tests to compare their uniformity of response to
      external irradiation under laboratory conditions; (3) field tests of their
      durability when worn on wildlife under natural conditions; and (4) a field
      application of the new technology at a radioactively contaminated site. Use of
      coupled GPS-dosimetry will allow, for the first time, researchers to better
      understand the relationship of animals to their contaminated habitats and better
      assess animal responses to the stress of radiological exposures. 

PMID- 25863718
TI  - Intrinsic and task-dependent coupling of neuronal population activity in human
      parietal cortex.
AB  - Human neuroimaging studies have suggested that subregions of the medial and
      lateral parietal cortex form key nodes of a larger brain network supporting
      episodic memory retrieval. To explore the electrophysiological correlates of
      functional connectivity between these subregions, we recorded simultaneously from
      medial and lateral parietal cortex using intracranial electrodes in three human
      subjects. We observed electrophysiological co-activation of
      retrosplenial/posterior cingulate cortex (RSC/PCC) and angular gyrus (AG) in the
      high-frequency broadband (HFB, or high-gamma) range, for conditions that required
      episodic retrieval. During resting and sleeping states, slow fluctuations (<1 Hz)
      of HFB activity were highly correlated between these task-co-activated neuronal
      populations. Furthermore, intrinsic electrophysiological connectivity patterns
      matched those obtained with resting-state fMRI from the same subjects. Our
      findings quantify the spatiotemporal dynamics of parietal cortex during episodic
      memory retrieval and provide clear neurophysiological correlates of intrinsic and
      task-dependent functional connectivity in the human brain.

PMID- 25863722
TI  - Bilateral Asymmetry of Radius and Tibia Bone Macroarchitecture and
      Microarchitecture: A High-Resolution Peripheral Quantitative Computed Tomography
      Study.
AB  - Studies assessing bone health often select the dominant or nondominant limb to
      scan, but not both, for efficiency reasons. New scanning technology allows 3
      dimensional (3D) visualization of the microarchitecture in bone, but it is not
      well understood whether there are differences between the dominant and
      nondominant limbs. Using 3D high-resolution peripheral quantitative computed
      tomography (HR-pQCT), the aim of this study is to investigate the effect of limb
      dominance on bone macroarchitecture and microarchitecture. Healthy male and
      female participants (N=100; 59 female, 41 male), mean age 30.7+/-12.1 years, were
      scanned at both radii and tibiae using HR-pQCT. Hand and foot dominance were
      determined by the participant's self-report. Most participants were right hand
      dominant (94.0%) and right foot dominant (91.0%). In the pooled cohort, the
      dominant radius had significantly greater cortical area (2.11%; p=0.002) and
      failure load (3.00%; p=0.001). At the tibia, the dominant foot had significantly
      lower bone mineral density (-0.77%; p=0.042), cortical area (-1.05%; p=0.031),
      and thickness (-1.51%; p=0.017). For females, there were no differences at the
      radius, but at the tibia, the dominant side had greater cross-sectional area
      (1.03%; p=0.044). Our data suggest that dominance has a small yet significant
      effect on macroarchitecture at both the ultradistal radius and tibia but not
      microarchitecture. This work emphasizes that it is important to be consistent in
      the selection of either dominant or nondominant limbs for HR-pQCT cohort studies;
      however, in the case where the opposite limb needs to be scanned, there would be
      small differences in macroarchitecture and no significant differences in
      microarchitecture anticipated.

PMID- 25863723
TI  - Best of enemies: Using social network analysis to explore a policy network in
      European smoke-free policy.
AB  - Networks and coalitions of stakeholders play a crucial role in the development
      and implementation of policies, with previous research highlighting that networks
      in tobacco control are characterised by an antagonism between supporters and
      opponents of comprehensive tobacco control policies. This UK-based study used
      quantitative and qualitative network analysis (drawing on 176 policy submissions
      and 32 interviews) to systematically map and analyse a network of actors involved
      in the development of European Union (EU) smoke-free policy. Policy debates were
      dominated by two coalitions of stakeholders with starkly opposing positions on
      the issue. One coalition, consisting primarily of health-related organisations,
      supported comprehensive EU smoke-free policy, whereas the other, led by tobacco
      manufacturers' organisations, opposed the policy initiative. The data suggest
      that, aided by strong political commitment of EU decision makers to develop smoke
      free policy, advocates supporting comprehensive EU policy were able to frame
      policy debates in ways which challenged the tobacco industry's legitimacy. They
      then benefited from the stark polarisation between the two coalitions. The paper
      provides empirical evidence of the division between two distinct coalitions in
      tobacco policy debates and draws attention to the complex processes of consensus
      seeking, alliance-building and strategic action which are integral to the
      development of EU policy. Highlighting network polarisation and industry
      isolation as factors which seemed to increase tobacco control success, the study
      demonstrates the potential significance and value of FCTC article 5.3 for tobacco
      control policy-making. 

PMID- 25863724
TI  - Living arrangements as determinants of myocardial infarction incidence and
      survival: A prospective register study of over 300,000 Finnish men and women.
AB  - Living with a spouse is associated with a reduced risk of coronary heart disease
      mortality in middle age, but it remains unclear whether marriage and other living
      arrangements are important both for the development of the disease and the
      survival following incidence. Cohabitation and living alone have also become more
      common in many Western societies and thus warrant further study. We explored the
      association between living arrangements and myocardial infarction (MI) incidence
      and fatality. We used a population-based register sample of adults aged 40-60 in
      Finland in 1995 (n = 302,885) followed up until the end of 2007. MI incidence and
      mortality were identified from hospital discharge records and cause of death
      register (5917 incident cases in men and 1632 in women). Living with a marital
      partner was contrasted to three alternatives: cohabiting with non-marital
      partner, co-residence with persons other than a partner and living alone. MI
      incidence and long-term fatality were analysed with Cox proportional hazards
      regression with time-varying covariates and first-day fatality with logistic
      regression. Men who were married had a lower risk of MI incidence even after
      adjusting for socioeconomic factors - i.e. education, occupation, income, wealth
      and employment status - with small differences between the other living
      arrangement groups. For women the effects of living arrangements on incidence
      were fully explained by the same socioeconomic factors. However, our findings
      revealed that living arrangements were strong determinants for survival after MI
      independent of other socio-demographic factors. The results demonstrate greater
      fatality associated with living alone in men and suggest that cohabitation in
      midlife may be associated with a greater fatality risk in women. The social
      support and control offered by a marital relationship may protect from MI
      fatality in particular. 

PMID- 25863725
TI  - Comparison communities in a cluster randomised trial innovate in response to
      'being controlled'.
AB  - We conducted qualitative interviews among primary health care teams and community
      agencies in eight communities in Victoria, Australia which had (1) agreed to be
      part of a universal primary care and community development intervention to reduce
      post natal depression and promote maternal health; and (2) were randomised to the
      comparison arm. The purpose was to document their experience with and
      interpretation of the trial. Although 'control' in a controlled trial refers to
      the control of confounding of the trial result by factors other than allocation
      to the intervention, participants interpreted 'control' to mean restrictions on
      what they were allowed to do during the trial period. They had agreed not to use
      the Edinburgh Post Natal Depression Scale or the SF 36 in clinical practice and
      not to implement any of the elements of the intervention. We found that no
      elements of the intervention were implemented. However, the extension of the
      trial from three to five years made the trial agreement a strain. The imposition
      of trial conditions also encouraged a degree of lateral thinking and innovation
      in service delivery (quality improvement). This may have potentially contributed
      to the null trial results. The observations invite interrogation of intervention
      theory and consequent rethinking of the way contamination in a cluster trial is
      defined. 

PMID- 25863726
TI  - Redox theory of aging.
AB  - Metazoan genomes encode exposure memory systems to enhance survival and
      reproductive potential by providing mechanisms for an individual to adjust during
      lifespan to environmental resources and challenges. These systems are inherently
      redox networks, arising during evolution of complex systems with O2 as a major
      determinant of bioenergetics, metabolic and structural organization, defense, and
      reproduction. The network structure decreases flexibility from conception onward
      due to differentiation and cumulative responses to environment (exposome). The
      redox theory of aging is that aging is a decline in plasticity of genome-exposome
      interaction that occurs as a consequence of execution of differentiation and
      exposure memory systems. This includes compromised mitochondrial and bioenergetic
      flexibility, impaired food utilization and metabolic homeostasis, decreased
      barrier and defense capabilities and loss of reproductive fidelity and fecundity.
      This theory accounts for hallmarks of aging, including failure to maintain
      oxidative or xenobiotic defenses, mitochondrial integrity, proteostasis, barrier
      structures, DNA repair, telomeres, immune function, metabolic regulation and
      regenerative capacity. 

PMID- 25863727
TI  - Orthopaedic Residents Improve Confidence and Knot-Tying Speed With a Skills
      Course.
AB  - PURPOSE: To determine the effect of a knot-tying module, within an arthroscopic
      training course, on resident speed, resident confidence, and biomechanical
      quality of arthroscopically tied knots. METHODS: Sixty-four participants (8
      postgraduate year [PGY]-3 and 8 PGY-4 orthopaedic residents annually for 4 years)
      were enrolled in a 5-day training course, which included a daily knot-tying
      module. Self-assessed confidence was obtained by pre-course (day 1) and post
      course (day 5) questionnaire. Each participant tied 5 sequential knots using an
      arthroscopic knot-tying station. Time per knot was recorded in seconds. Knots
      were later preloaded, cycled, and tested for peak load to failure and
      displacement change. Mean peak load to failure, displacement change, speed, and
      confidence were compared before and after training. RESULTS: The mean time to
      complete 5 knots was significantly faster after training (12.8 minutes before the
      course [day 1] v 9.39 minutes after the course [day 5]) (P < .0001). Confidence
      improved from pre-course (mean, 3.3) to post-course (mean, 7.8) questionnaires (P
      < .0001). No statistically significant difference was found between peak force
      for pre-course (mean, 136 N) and post-course (mean, 138 N) knots (P = .076). No
      statistically significant difference was detected in mean displacement change
      (mean, 3.51 mm before the course v 3.57 mm after the course) (P = .61).
      Comparison of PGY-3 and PGY-4 residents was significant only for a higher pre
      course confidence in PGY-4 residents (P = .02). CONCLUSIONS: Participation in an
      arthroscopic knot-tying module improves resident speed and confidence in tying
      arthroscopic knots. Our data did not show a significant change in peak load to
      failure or loop security with training. These findings suggest that participation
      in a knot-tying module improves efficiency regarding arthroscopic knot tying by
      residents. CLINICAL RELEVANCE: Residents who practice arthroscopic knot tying 5
      days per year as part of an arthroscopic training course may be more efficient in
      the operating room.

PMID- 25863728
TI  - Double-lumen tube for use with a tracheostomy.

PMID- 25863729
TI  - Double-lumen tubes for tracheostomized patients.

PMID- 25863730
TI  - CASE 6-2015: Penetrating Biventricular Cardiac Injury in a Trauma Patient: Heart
      Versus Machete.

PMID- 25863731
TI  - Resident Perceptions of 2-Year Versus 3-Year Cardiothoracic Training Programs.
AB  - BACKGROUND: Resident perceptions of 2-year (2Y) vs 3-year (3Y) programs have
      never been characterized. The objective was to use the mandatory Thoracic Surgery
      Residents Association and Thoracic Surgery Directors Association In-Training
      Examination survey to compare perceptions of residents graduating from 2Y vs 3Y
      cardiothoracic programs. METHODS: Each year Accreditation Council for Graduate
      Medical Education cardiothoracic residents are required to take a 30-question
      survey designed by the Thoracic Surgery Residents Association and the Thoracic
      Surgery Directors Association accompanying the In-Training Examination with a
      100% response rate. The 2013 and 2014 survey responses of residents graduating
      from 2Y vs 3Y training programs were compared. The Wilcoxon signed rank test was
      used to analyze ordinal and interval data. RESULTS: Graduating residents
      completed 167 surveys, including 96 from 2Y (56%) and 71 from 3Y (43%) programs.
      There was no difference in the perception of being prepared for the American
      Board of Thoracic Surgery examinations or amount of debt between 2Y and 3Y
      respondents. There was no difference in intended academic vs private practice.
      Graduating 3Y residents felt more prepared to meet case requirements and better
      trained, were more likely to pass their written American Board of Thoracic
      Surgery examinations, and were less likely to pursue additional training beyond
      their cardiothoracic residency. CONCLUSIONS: There was no difference in field of
      interest, practice type, and amount of debt between graduating 2Y vs 3Y
      residents. Respondents from 2Y programs expressed more difficulty in meeting case
      requirements, whereas residents from 3Y programs felt more prepared for
      independent practice and had higher American Board of Thoracic Surgery written
      pass rates.

PMID- 25863732
TI  - Myocardial Injury After Transaortic Versus Transapical Transcatheter Aortic Valve
      Replacement.
AB  - BACKGROUND: The release of cardiac biomarkers of myocardial injury after
      transcatheter aortic valve replacement (TAVR) is common, but no data exist on
      patients undergoing TAVR through a transaortic approach. We aimed to evaluate the
      incidence and prognostic significance of the increase in cardiac biomarkers in
      nontransfemoral TAVR candidates, comparing transaortic and transapical
      approaches. METHODS: After excluding patients deemed suitable for transfemoral
      TAVR, 251 consecutive patients (transaortic, 45; transapical, 206) were
      prospectively evaluated. Creatine kinase-myocardial band and cardiac troponin T
      levels were measured at baseline and at 6, 12, 24, 48, and 72 hours after TAVR.
      Baseline and 6- to 12-month echocardiographic and clinical follow-up were
      performed. RESULTS: After TAVR, cardiac troponin T increased above the upper
      normal values in all patients (peak value 0.64 MUg/L [IQR, 0.39 to 1.03 MUg/L]),
      whereas creatine kinase-myocardial band levels increased in 88% of patients
      (transaortic 51%, transapical 96%, p < 0.001; peak value 20.1 MUg/L
      [interquartile range, 14.3 to 31.6 MUg/L]). Compared with the transaortic
      approach, the transapical approach was associated with a greater rise in both
      cardiac biomarkers (p < 0.001 for both), and a lesser improvement in left
      ventricular ejection fraction (p = 0.058) and global longitudinal strain (p =
      0.039) at 6- to 12-month follow-up. Greater increases of cardiac troponin T
      levels were independently associated with 30-day and 1-year overall and
      cardiovascular mortality (p < 0.001 for all). A 15-fold rise in cardiac troponin
      T levels was the optimal threshold for determining poorer outcomes (p < 0.001).
      CONCLUSIONS: Periprocedural TAVR-related myocardial injury in nontransfemoral
      candidates was demonstrated in all patients, but the transapical approach was
      associated with significantly greater myocardial injury compared with the
      transaortic approach. A higher degree of myocardial injury translated into
      reduced left ventricular function improvement and lower early and midterm
      survival rates.

PMID- 25863733
TI  - Risperidone unmasking an accessory pathway.

PMID- 25863734
TI  - Multicenter trials, guidelines, and uncertainties - Do we know as much as we
      think we do?
AB  - There is an uncritical belief that "positive" large scale multicenter randomized
      clinical trials provide a definitive window to the "truth". The limitations and
      difficulties in performing large trials are discussed herein and the need to
      fully and transparently acknowledge residual uncertainties is stressed. For
      example, the failure to consider the regional variations that may arise with the
      "outsourcing" of trials may lead to false estimates of precision. As large trials
      form the backbone of guidelines, failure to critically evaluate the importance of
      evidential limitations may see a minimization of residual uncertainties and lead
      to inappropriate recommendations. 

PMID- 25863735
TI  - Atrial fibrillation and rapid acute pacing regulate adipocyte/adipositas-related
      gene expression in the atria.
AB  - PURPOSE: Atrial fibrillation (AF) has been associated with increased volumes of
      epicardial fat and atrial adipocyte accumulation. Underlying mechanisms are not
      well understood. This study aims to identify rapid atrial pacing (RAP)/AF
      dependent changes in atrial adipocyte/adipositas-related gene expression (AARE).
      METHODS: Right atrial (RA) and adjacent epicardial adipose tissue (EAT) samples
      were obtained from 26 patients; 13 with AF, 13 in sinus rhythm (SR). Left atrial
      (LA) samples were obtained from 9 pigs (5 RAP, 4 sham-operated controls). AARE
      was analyzed using microarrays and RT-qPCR. The impact of diabetes/obesity on
      gene expression was additionally determined in RA samples (RAP ex vivo and
      controls) from 3 vs. 6 months old ZDF rats. RESULTS: RAP in vivo of pigs resulted
      in substantial changes of AARE, with 66 genes being up- and 53 down-regulated on
      the mRNA level. Differential expression during adipocyte differentiation was
      confirmed using 3T3-L1 cells. In patients with AF (compared to SR), a comparable
      change in RA mRNA levels concerned a fraction of genes only (RETN, IGF1, HK2,
      PYGM, LOX, and NR4A3). RA and EAT were affected by AF to a different extent. In
      patients, concomitant disease contributes to AARE changes. CONCLUSIONS: RAP, and
      to lesser extent AF, provoke significant changes in atrial AARE. In chronic AF,
      activation of this gene panel is very likely mediated by AF itself, AF risk
      factors and concomitant diseases. This may facilitate the development of an AF
      substrate by increasing atrial ectopic fat and fat infiltration of the atrial
      myocardium.

PMID- 25863736
TI  - Symptoms of depression and anxiety predict mortality in patients undergoing oral
      anticoagulation: Results from the thrombEVAL study program.
AB  - BACKGROUND/OBJECTIVES: Depression and anxiety are highly prevalent in
      cardiovascular patients. Therefore, we examined whether the 4-item Patient Health
      Questionnaire (PHQ-4, measuring symptoms of depression and anxiety) predicts all
      cause mortality in outpatients with long-term oral anticoagulation (OAC).
      METHODS: The sample comprised n=1384 outpatients from a regular medical care
      setting receiving long-term OAC with vitamin K antagonists. At baseline, symptoms
      of anxiety and depression were assessed with the PHQ-4 and the past medical
      history was taken. The outcome was all-cause mortality in the 24 month
      observation period. The median follow-up time was 13.3 months. RESULTS: N=191
      patients from n=1384 died (death rate 13.8%). Each point increase in the PHQ-4
      score was associated with a 10% increase in mortality (hazard ratio [HR] 1.10,
      95% confidence interval [95% CI] 1.05-1.16) after adjustment for age, sex, high
      school graduation, partnership, smoking, obesity, frailty according to the
      Barthel Index, Charlson Comorbidity Index and CHA2DS2-VASc score. The depression
      component (PHQ-2) increased mortality by 22% and anxiety (GAD-2) by 11%
      respectively. Neither medical history of any mental disorder, nor intake of
      antidepressants, anxiolytics or hypnotics predicted excess mortality.
      CONCLUSIONS: Elevated symptoms of depression and, to a lesser degree, symptoms of
      anxiety are independently associated with all-cause mortality in OAC outpatients.
      The PHQ-4 questionnaire provides valuable prognostic information. These findings
      emphasize the need for implementing regular screening procedures and the
      development and evaluation of appropriate psychosocial treatment approaches for
      OAC patients.

PMID- 25863737
TI  - ECMO as a bridge to decision: Recovery, VAD, or heart transplantation?
AB  - BACKGROUND: Our 8-year experience with ECMO support as a bridge to decision was
      reviewed. METHODS: A cohort of 124 consecutive patients received ECMO for
      refractory cardiogenic shock in our institution. Twenty-six of these were out of
      hospital cardiac arrests and were excluded from this analysis. The median age was
      43 years, in the range of 11 to 73 years. RESULTS: The median duration of ECMO
      support was 4.5 days. Mortality while supported by ECMO was 50% with a median
      support time of 2 days. Weaning from ECMO was achieved for 49 patients with the
      following outcomes: cardiac recovery (60%), heart transplantation (26%), and VAD
      implantation (14%). Median duration of support before weaning was 8 days.
      Hospital survival was 83%, 61.5% and 71% for cardiac recovery, heart
      transplantation and VAD implantation, respectively. ECMO weaning was
      significantly improved in all patients who had normalized their renal function,
      and when duration of support>6 days (HR: 4.255 [1.255-14.493], p=0.02 and HR:
      2.164 [1.152-4.082], p=0.02, respectively). A creatinine level>14 mg/l the day of
      weaning was a significant predictor of death (HR: 5.807 [1.089-30.953]; p=0.04).
      Median follow up was 2.4 years; one-year survival rate was 78%, 51% and 75% for
      cardiac recovery, heart transplantation and VAD implantation, respectively.
      CONCLUSION: With at least 6 days of support, ECMO allowed a better patient
      selection for myocardial recovery, VAD implantation or heart transplantation.
      Whether VAD implantation or heart transplant in those patients is a better
      indication remains to be evaluated.

PMID- 25863738
TI  - Non-linear association of periodontal pathogen antibodies with mortality.
AB  - BACKGROUND: Periodontal pathogens are associated with predisposition to chronic
      diseases and death. Antibody levels against them reflect flora burden, although
      high levels might indicate a protective response. We studied all-cause and cause
      specific mortality in relation to antibody levels in a representative US sample.
      METHODS: Adults >= 20 years (n=6993) from the second phase of the Third National
      Health and Nutrition Examination Survey (NHANES III) were followed for a median
      of 13.2 years. Serum antibodies against Porphyromonas gingivalis (antiPG) and
      Actinobacillus actinomycetemcomitans (antiAA) were quantified by ELISA at
      baseline (1991-1994). Mortality hazard ratios (HRs) were calculated across
      antibody quartiles using the quartile with highest mortality as reference.
      RESULTS: Median (25th, 75th percentiles) antiPG was 72 (63, 93) ELISA Units (EU)
      and median antiAA was 70 (64, 89) EU. After adjustment for potential confounders,
      mortality was highest for participants with antibodies in the third antiPG
      quartile (72-92 EU), with lower mortality risk for values not only below but also
      above this range [HR for the 1st to 4th quartiles: 0.81 (95% CI: 0.65, 1.01),
      0.67 (95% CI: 0.55, 0.82), 1.00 (Reference), 0.79 (95% CI: 0.64, 0.97)]. In
      spline regression models the association had an inverted U-shape and mortality
      exhibited a peak at 84 EU (67th percentile). Mortality was not associated with
      antiAA. CONCLUSIONS: Mortality was highest for those just above the median antiPG
      and a reduced risk was present among those with low or high levels of the
      antibody. Future studies should confirm this downward trend in upper levels and
      investigate a potential protective role of immunity against P. gingivalis.

PMID- 25863739
TI  - Noninvasive vagal nerve stimulation for heart failure: Was it practical or just a
      stunt?

PMID- 25863740
TI  - Chronic giant post-traumatic pseudoaneurysm of the right ventricular outflow
      tract associated with penetrating ventricular septal fistula.

PMID- 25863741
TI  - Excess winter deaths caused by cardiovascular diseases are associated with both
      mild winter temperature and socio-economic inequalities in the U.S.

PMID- 25863742
TI  - Are direct oral anticoagulants equally effective in reducing deep vein thrombosis
      and pulmonary embolism?

PMID- 25863743
TI  - Efficient induction of anti-tumor immune response in esophageal squamous cell
      carcinoma via dendritic cells expressing MAGE-A3 and CALR antigens.
AB  - Despite advances in the various treatment options for esophageal squamous cell
      carcinoma (ESCC), its prognosis is still very poor with a 5-year survival rate of
      only 14-22%. Recently, among the various therapeutic approaches, the focus has
      shifted to immunotherapy, specifically immunotherapy involving dendritic cells
      (DCs), which depends on their maturation and antigen presentation to effector
      immune cells. Recent studies have suggested that melanoma-associated antigen 3
      (MAGE-A3) is a potential immunotherapeutic target and also a candidate for the
      development of an anti-tumor vaccine. Calreticulin (CALR) has been shown to
      support induction of DC maturation. Therefore, in this study, we overexpressed
      MAGE-A3 and CALR on DCs and studied their potential to generate anti-tumor immune
      responses. We observed that adenovirus (Ad)-infected DCs overexpressing CALR and
      MAGE-A3 showed enhanced expression of CD80, CD83, CD86, and HLA-DR markers. Also,
      these DCs secreted higher levels of interleukin (IL)-12, which induces the T
      helper type 1 cell (Th1) response, and a lower level of IL-10, a negative
      regulator of the Th1 response. Furthermore, CALR/MAGE-A3-infected DCs stimulated
      CD8(+) cytotoxic T lymphocytes, which in turn secreted higher levels of
      interferon-gamma, which induced cytotoxic effects on ESCC cells expressing MAGE
      A3. In conclusion, our results revealed the potential of CALR/MAGE-A3-infected
      DCs to elicit a MAGE-A3-specific anti-tumor immunogenic response in ESCC. This
      proof-of-principle study may promote the future design and development of DC
      based effective immunotherapy against ESCC. 

PMID- 25863745
TI  - Comment on "delayed myelination is not a constant feature of Allan-Herndon-Dudley
      syndrome: report of a new case and review of the literature" by Azzolini S et al.
      Brain & Development 2014;36:716-720.

PMID- 25863744
TI  - Chlamydia pneumoniae promotes dysfunction of pancreatic beta cells.
AB  - The human pathogen Chlamydia pneumoniae has been implicated in chronic
      inflammatory diseases including type 2 diabetes. Therefore, we designed a study
      to evaluate pancreatic beta cells and mast cells during chlamydial infection. Our
      study revealed that C. pneumoniae infected mast cells significantly (p<0.005)
      decreased beta cell ATP and insulin production, in contrast to uninfected mast
      cells co-cultured with beta cells. Infected mast cells exhibited pyknotic nuclei
      and active caspase-3 and caspase-1 expression. Additionally, ex vivo analyses of
      tissues collected from C. pneumoniae infected mice showed increased interleukin
      1beta production in splenocytes and pancreatic tissues as was observed with in
      vitro mast cell-beta cell co-cultures during C. pneumoniae infection. Notably,
      infected mast cells promoted beta cell destruction. Our findings reveal the
      negative effect of C. pneumoniae on mast cells, and the consequential impact on
      pancreatic beta cell function and viability. 

PMID- 25863746
TI  - Fifty years from Paris: the remarkable story of the lymphomas.

PMID- 25863747
TI  - The Paris conference "La Radiotherapie de la Maladie de Hodgkin": a first step in
      the cure of Hodgkin disease.

PMID- 25863748
TI  - Homage to M. Vera Peters, MD.

PMID- 25863749
TI  - Dorothy Reed Mendenhall: expressions of a pioneer in Hodgkin disease.

PMID- 25863750
TI  - Modern radiation therapy for extranodal lymphomas: field and dose guidelines from
      the International Lymphoma Radiation Oncology Group.
AB  - Extranodal lymphomas (ENLs) comprise about a third of all non-Hodgkin lymphomas
      (NHL). Radiation therapy (RT) is frequently used as either primary therapy
      (particularly for indolent ENL), consolidation after systemic therapy, salvage
      treatment, or palliation. The wide range of presentations of ENL, involving any
      organ in the body and the spectrum of histological sub-types, poses a challenge
      both for routine clinical care and for the conduct of prospective and
      retrospective studies. This has led to uncertainty and lack of consistency in RT
      approaches between centers and clinicians. Thus far there is a lack of guidelines
      for the use of RT in the management of ENL. This report presents an effort by the
      International Lymphoma Radiation Oncology Group (ILROG) to harmonize and
      standardize the principles of treatment of ENL, and to address the technical
      challenges of simulation, volume definition and treatment planning for the most
      frequently involved organs. Specifically, detailed recommendations for RT volumes
      are provided. We have applied the same modern principles of involved site
      radiation therapy as previously developed and published as guidelines for Hodgkin
      lymphoma and nodal NHL. We have adopted RT volume definitions based on the
      International Commission on Radiation Units and Measurements (ICRU), as has been
      widely adopted by the field of radiation oncology for solid tumors. Organ
      specific recommendations take into account histological subtype, anatomy, the
      treatment intent, and other treatment modalities that may be have been used
      before RT. 

PMID- 25863751
TI  - Modern radiation therapy for primary cutaneous lymphomas: field and dose
      guidelines from the International Lymphoma Radiation Oncology Group.
AB  - Primary cutaneous lymphomas are a heterogeneous group of diseases. They often
      remain localized, and they generally have a more indolent course and a better
      prognosis than lymphomas in other locations. They are highly radiosensitive, and
      radiation therapy is an important part of the treatment, either as the sole
      treatment or as part of a multimodality approach. Radiation therapy of primary
      cutaneous lymphomas requires the use of special techniques that form the focus of
      these guidelines. The International Lymphoma Radiation Oncology Group has
      developed these guidelines after multinational meetings and analysis of available
      evidence. The guidelines represent an agreed consensus view of the International
      Lymphoma Radiation Oncology Group steering committee on the use of radiation
      therapy in primary cutaneous lymphomas in the modern era. 

PMID- 25863752
TI  - Expert radiation oncologist interpretations of involved-site radiation therapy
      guidelines in the management of Hodgkin lymphoma.
AB  - PURPOSE: Recently, involved-site radiation therapy (ISRT) guidelines have been
      developed and published to replace the previous concept of involved-field
      radiation therapy for patients with lymphoma. However, these ISRT guidelines may
      be interpreted in different ways, posing difficulties for prospective clinical
      trials. This study reports survey results regarding interpretation of the ISRT
      guidelines. METHODS AND MATERIALS: Forty-four expert lymphoma radiation
      oncologists were asked to participate in a survey that included 7 different cases
      associated with 9 questions. The questions pertained to ISRT contouring and asked
      respondents to choose between 2 different answers (no "correct" answer) and a
      third write-in option allowed. RESULTS: Fifty-two percent of those surveyed
      responded to the questionnaire. Among those who responded, 72% have practiced for
      >10 years, 46% have treated >20 Hodgkin lymphoma cases annually, and 100% were
      familiar with the ISRT concept. Among the 9 questions associated with the 7
      cases, 3 had concordance among the expert radiation oncologists of greater than
      70%. Six of the questions had less than 70% concordance (range, 56%-67%).
      CONCLUSIONS: Even among expert radiation oncologists, interpretation of ISRT
      guidelines is variable. Further guidance for ISRT field design will be needed to
      reduce variability among practicing physicians.

PMID- 25863753
TI  - Relapse analysis of irradiated patients within the HD15 trial of the German
      Hodgkin Study Group.
AB  - PURPOSE: To determine, in the setting of advanced-stage of Hodgkin lymphoma (HL),
      whether relapses occur in the irradiated planning target volume and whether the
      definition of local radiation therapy (RT) used by the German Hodgkin Study Group
      (GHSG) is adequate, because there is no harmonization of field and volume
      definitions among the large cooperative groups in the treatment of advanced-stage
      HL. METHODS AND MATERIALS: All patients with residual disease of >= 2.5 cm after
      multiagent chemotherapy (CTX) were evaluated using additional positron emission
      tomography (PET), and those with a PET-positive result were irradiated with 30 Gy
      to the site of residual disease. We re-evaluated all sites of disease before and
      after CTX, as well as the PET-positive residual tumor that was treated in all
      relapsed patients. Documentation of radiation therapy (RT), treatment planning
      procedures, and portal images were carefully analyzed and compared with the
      centrally recommended RT prescription. The irradiated sites were compared with
      sites of relapse using follow-up computed tomography scans. RESULTS: A total of
      2126 patients were enrolled, and 225 patients (11%) received RT. Radiation
      therapy documents of 152 irradiated patients (68%) were analyzed, with 28
      irradiated patients (11%) relapsing subsequently. Eleven patients (39%) had an in
      field relapse, 7 patients (25%) relapsed outside the irradiated volume, and an
      additional 10 patients (36%) showed mixed in- and out-field relapses. Of 123
      patients, 20 (16%) with adequately performed RT relapsed, compared with 7 of 29
      patients (24%) with inadequate RT. CONCLUSIONS: The frequency and pattern of
      relapses suggest that local RT to PET-positive residual disease is sufficient for
      patients in advanced-stage HL. Insufficient safety margins of local RT may
      contribute to in-field relapses.

PMID- 25863754
TI  - Low-dose consolidation radiation therapy for early stage unfavorable Hodgkin
      lymphoma.
AB  - PURPOSE: The German Hodgkin Study Group (GHSG) trial HD11 established 4 cycles of
      doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and 30 Gy of
      radiation therapy (RT) as a standard for early stage (I, II), unfavorable Hodgkin
      lymphoma (HL). Additional cycles of ABVD may allow for a reduction in RT dose and
      improved toxicity profile. METHODS AND MATERIALS: Patients treated with combined
      modality therapy at the Duke Cancer Institute for early stage, unfavorable HL by
      GHSG criteria from 1994 to 2012 were included. Patients who did not undergo post
      chemotherapy functional imaging (positron emission tomography or gallium imaging)
      or who failed to achieve a complete response were excluded. Clinical outcomes
      were estimated using the Kaplan-Meier method. Late effects were also evaluated.
      RESULTS: A total of 90 patients met inclusion criteria for analysis. Median
      follow-up was 5 years. Chemotherapy consisted primarily of ABVD (88%) with a
      median number of 6 cycles. The median dose of consolidation RT was 23.4 Gy. Four
      patients had relapses, 2 of which were in-field. Ten-year progression-free
      survival (PFS) and overall survival (OS) were 93% (95% confidence interval [CI]:
      0.82-0.97) and 98% (95% CI: 0.92-0.99), respectively. For the subset of patients
      (n=46) who received 5 to 6 cycles of chemotherapy and <= 24 Gy, the 10-year PFS
      and OS values were 88% (95% CI: 70%-96%) and 98% (95% CI: 85% - 99%),
      respectively. The most common late effect was hypothyroidism (20%) with no
      cardiac complications. Seven secondary malignancies were diagnosed, with only 1
      arising within the RT field. CONCLUSIONS: Lower doses of RT may be sufficient
      when combined with more than 4 cycles of ABVD for early stage, unfavorable HL and
      may result in a more favorable toxicity profile than 4 cycles of ABVD and 30 Gy
      of RT.

PMID- 25863755
TI  - Management of nodular lymphocyte predominant Hodgkin lymphoma in the modern era.
AB  - PURPOSE: To analyze treatment outcomes for nodular lymphocyte predominant Hodgkin
      lymphoma (NLPHL) at a single institution. PATIENTS AND METHODS: Patients with
      newly diagnosed NLPHL between 1996 and 2013 were reviewed retrospectively.
      Patients treated before 1996 were excluded because the majority received extended
      field radiation therapy (RT) alone. RESULTS: Fifty-five patients (22 <= 21 years
      old) were identified. The median follow-up time was 6.8 years. Among 37 patients
      with limited-stage (I-II) disease, treatments included involved field RT at a
      median dose of 36 Gy (n=9), rituximab monotherapy (n=9), observation (n=3), and
      response-adaptive therapy (n=16), in which the RT dose was reduced from 25.5 Gy
      to 15 Gy or was eliminated based on interim imaging after chemotherapy. The 5
      year progression-free survival (PFS) was 76.4% (95% confidence interval [CI],
      63.1-92.4). Nine patients experienced progression, including 5 receiving
      rituximab, 2 undergoing observation, and 2 receiving response-adaptive therapy.
      Rituximab was associated with an inferior PFS compared with RT alone (P=.02). The
      difference in PFS between response-adaptive therapy and RT alone was not
      statistically significant (P=.39). Among 18 patients with advanced-stage (III-IV)
      disease, treatments included chemotherapy alone (n=3), combined modality therapy
      (CMT) (n=2), response-adaptive therapy (n=2), rituximab (n=7), and observation
      (n=4). The 5-year PFS was 29.9% (CI, 13.3-67.4). Twelve patients experienced
      progression, including 1 receiving chemotherapy, 1 receiving CMT, 6 receiving
      rituximab, and 4 undergoing observation. There was no significant PFS difference
      between rituximab and non-rituximab therapies (P=.19) within the caveat of small
      sample sizes. In the entire cohort, 9 patients (3 with limited disease, 6 with
      advanced disease) experienced large cell transformation (LCT). Seven patients
      died; of those, 5 died with LCT. CONCLUSIONS: For limited disease, response
      adaptive therapy demonstrated comparable outcomes with RT alone. Rituximab
      monotherapy resulted in inferior outcomes for limited disease and a high relapse
      rate for advanced disease.

PMID- 25863756
TI  - Characteristics and outcomes of patients with nodular lymphocyte-predominant
      Hodgkin lymphoma versus those with classical Hodgkin lymphoma: a population-based
      analysis.
AB  - PURPOSE: Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is rare,
      comprising approximately 5% of all Hodgkin lymphoma (HL) cases. Patients with
      NLPHL tend to have better prognoses than those with classical HL (CHL). Our goal
      was to assess differences in survival between NLPHL and CHL patients, controlling
      for differences in patient and disease characteristics. METHODS AND MATERIALS:
      Using data from the population-based Surveillance, Epidemiology and End Results
      (SEER) cancer registry program, we identified patients diagnosed with
      pathologically confirmed HL between 1988 and 2010. RESULTS: We identified 1,162
      patients with NLPHL and 29,083 patients with CHL. With a median follow-up of 7
      years, 5- and 10-year overall survival (OS) rates were 91% and 83% for NLPHL,
      respectively, and 81% and 74% for CHL, respectively. After adjusting for all
      available characteristics, NLPHL (vs CHL) was associated with higher OS (hazard
      ratio [HR]: 0.62, P<.01) and disease-specific survival (DSS; HR: 0.48, P<.01).
      The male predominance of NLPHL, compared to CHL, as well as the more favorable
      prognostic features in NLPHL patients are most pronounced in NLPHL patients <20
      years old. Among all NLPHL patients, younger patients were less likely to receive
      radiation, and radiation use has declined by 40% for all patients from 1988 to
      2010. Receipt of radiation was associated with better OS (HR: 0.64, P=.03) and
      DSS (HR: 0.45, P=.01) in NLPHL patients after controlling for available baseline
      characteristics. Other factors associated with OS and DSS in NLPHL patients are
      younger age and early stage. CONCLUSIONS: Our results in a large population
      dataset demonstrated that NLPHL patients have improved prognosis compared to CHL
      patients, even after accounting for stage and baseline characteristics. Use of
      radiation is declining among NLPHL patients despite an association in this series
      between radiation and better DSS and OS. Unique treatment strategies for NLPHL
      are warranted in both early and advanced stage disease.

PMID- 25863757
TI  - Value of surveillance studies for patients with stage I to II diffuse large B
      cell lymphoma in the rituximab era.
AB  - BACKGROUND: The role of surveillance studies in limited-stage diffuse large B
      cell lymphoma (DLBCL) in the rituximab era has not been well defined. We sought
      to evaluate the use of imaging (computed tomography [CT] and positron emission
      tomography [PET]-CT) scans and lactate dehydrogenase (LDH) in surveillance of
      patients with stage I to II DLBCL. METHODS: A retrospective analysis was
      performed of patients who received definitive treatment between 2000 and 2013.
      RESULTS: One hundred sixty-two consecutive patients with stage I to II DLBCL were
      treated with chemotherapy +/- rituximab, radiation, or combined modality therapy.
      The 5-year rates of overall survival (OS) and freedom from progression (FFP) were
      81.2% and 80.8%, respectively. Of the 162 patients, 124 (77%) were followed up
      with at least 1 surveillance PET scan beyond end-of-treatment scans; of those, 94
      of 124 (76%) achieved a complete metabolic response on PET scan after completion
      of chemotherapy, and this was associated with superior FFP (P=.01, HR=0.3) and OS
      (P=.01, HR 0.3). Eighteen patients experienced relapse after initial response to
      therapy. Nine relapses were initially suspected by surveillance imaging studies
      (8 PET, 1 CT), and 9 were suspected clinically (5 by patient-reported symptoms
      and 4 by symptoms and physical examination). No relapses were detected by
      surveillance LDH. The median duration from initiation of treatment to relapse was
      14.3 months among patients with relapses suspected by imaging, and 59.8 months
      among patients with relapses suspected clinically (P=.077). There was no
      significant difference in OS from date of first therapy or OS after relapse
      between patients whose relapse was suspected by imaging versus clinically.
      Thirteen of 18 patients underwent successful salvage therapy after relapse.
      CONCLUSIONS: A complete response on PET scan immediately after initial
      chemotherapy is associated with superior FFP and OS in stage I to II DLBCL. The
      use of PET scans as posttreatment surveillance is not associated with a survival
      advantage. LDH is not a sensitive marker for relapse. Our results argue for
      limiting the use of posttreatment surveillance in patients with limited-stage
      DLBCL.

PMID- 25863758
TI  - Predictors of local recurrence after rituximab-based chemotherapy alone in stage
      III and IV diffuse large B-cell lymphoma: guiding decisions for consolidative
      radiation.
AB  - PURPOSE: The role of consolidative radiation therapy (RT) for stage III and IV
      diffuse large B-cell lymphoma (DLBCL) in the era of rituximab is not well
      defined. There is evidence that some patients with bulky disease may benefit, but
      patient selection criteria are not well established. We sought to identify a
      subset of patients who experienced a high local failure rate after receiving
      rituximab-based chemotherapy alone and hence may benefit from the addition of
      consolidative RT. METHODS AND MATERIALS: Two hundred eleven patients with stage
      III and IV DLBCL treated between August 1999 and January 2012 were reviewed. Of
      these, 89 had a complete response to systemic therapy including rituximab and
      received no initial RT. Kaplan-Meier analysis and Cox proportional hazards
      regression were performed, with local recurrence (LR) as the primary outcome.
      RESULTS: The median follow-up time was 43.9 months. Fifty percent of patients
      experienced LR at 5 years. In multivariate analysis, tumor >= 5 cm and stage III
      disease were associated with increased risk of LR. The 5-year LR-free survival
      was 47.4% for patients with >= 5-cm lesions versus 74.7% for patients with <5-cm
      lesions (P=.01). In patients with <5-cm tumors, the maximum standardized uptake
      value (SUVmax) was >= 15 in all patients with LR. The 5-year LR-free survival was
      100% in SUV<15 versus 68.8% in SUV >= 15 (P=.10). CONCLUSIONS: Advanced-stage
      DLBCL patients with stage III disease or with disease >= 5 cm appear to be at an
      increased risk for LR. Patients with <5-cm disease and SUVmax >= 15 may be at
      higher risk for LR. These patients may benefit from consolidative RT after
      chemoimmunotherapy.

PMID- 25863760
TI  - Long-term outcomes and patterns of relapse of early-stage extranodal marginal
      zone lymphoma treated with radiation therapy with curative intent.
AB  - PURPOSE: To report the long-term outcome and patterns of relapse of a large
      cohort of marginal zone lymphoma (MZL) patients treated with curative-intent
      radiation therapy (RT) alone. PATIENTS AND METHODS: We reviewed the charts of 490
      consecutive patients with stage IE or IIE MZL referred between 1992 and 2012 to
      our institution. Of those, 244 patients (50%) were treated with RT alone.
      Pathology was confirmed by hematopathologists at our institution. Patient and
      disease factors were analyzed for association with relapse-free survival (RFS)
      and overall survival (OS). RESULTS: Median age of the cohort was 59 years, and
      median follow-up was 5.2 years. Ann Arbor stage was IE in 92%. Most common
      disease sites were stomach (50%), orbit (18%), non-thyroid head-and-neck (8%),
      skin (8%), and breast (5%). Median RT dose was 30 Gy. Five-year OS and RFS were
      92% and 74%, respectively. Cumulative incidence of disease-specific death was
      just 1.1% by 5 years. Sixty patients (24%) developed relapse of disease; 10 were
      in the RT field. Crude rate of transformation to pathologically confirmed large
      cell lymphoma was 1.6%. On multivariable analysis, primary disease site (P=.007)
      was independently associated with RFS, along with age (P=.04), presence of B
      symptoms (P=.02), and International Prognostic Index risk group (P=.03). All
      disease sites except for head-and-neck had worse RFS relative to stomach.
      CONCLUSION: Overall and cause-specific survival are high in early-stage extra
      nodal MZL treated with curative RT alone. In this large cohort of 244 patients,
      most patients did not experience relapse of MZL after curative RT; when relapses
      did occur, the majority were in distant sites. Stomach cases were less likely to
      relapse than other anatomic sites. Transformation to large-cell lymphoma was
      rare.

PMID- 25863759
TI  - Single-institution experience in the treatment of primary mediastinal B cell
      lymphoma treated with immunochemotherapy in the setting of response assessment by
      18fluorodeoxyglucose positron emission tomography.
AB  - PURPOSE: Excellent outcomes obtained after infusional dose-adjusted etoposide,
      doxorubicin, cyclophosphamide, vincristine, prednisone, and rituximab (R-EPOCH)
      alone have led some to question the role of consolidative radiation therapy (RT)
      in the treatment of primary mediastinal B cell lymphoma (PMBL). We reviewed the
      outcomes in patients treated with 1 of 3 rituximab-containing regimens
      (cyclophosphamide, doxorubicin, vincristine, prednisone [R-CHOP];
      hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone [R
      HCVAD], or R-EPOCH) with or without RT. We also evaluated the ability of positron
      emission tomography-computed tomography (PET-CT) to identify patients at risk of
      relapse. METHODS AND MATERIALS: We retrospectively identified 97 patients with
      diagnoses of stage I/II PMBCL treated at our institution between 2001 and 2013.
      The clinical characteristics, treatment outcomes, and toxicity were assessed. We
      analyzed whether postchemotherapy PET-CT could identify patients at risk for
      progressive disease according to a 5 point scale (5PS) Deauville score assigned.
      RESULTS: Among 97 patients (median follow-up time, 57 months), the 5-year overall
      survival rate was 99%. Of patients treated with R-CHOP, 99% received RT; R-HCVAD,
      82%; and R-EPOCH, 36%. Of 68 patients with evaluable end-of-chemotherapy PET-CT
      scans, 62% had a positive scan (avidity above that of the mediastinal blood pool
      [Deauville 5PS = 3]), but only 9 patients experienced relapse (n=1) or
      progressive disease (n=8), all with a 5PS of 4 to 5. Of the 25 patients who
      received R-EPOCH, 4 experienced progression, all with 5PS of 4 to 5; salvage
      therapy (RT and autologous stem cell transplantation) was successful in all
      cases. CONCLUSION: Combined modality immunochemotherapy and RT is well tolerated
      and effective for treatment of PMBCL. A postchemotherapy 5PS of 4 to 5, rather
      than 3 to 5, can identify patients at high risk of progression who should be
      considered for therapy beyond chemotherapy alone after R-EPOCH.

PMID- 25863761
TI  - Low-dose (10-Gy) total skin electron beam therapy for cutaneous T-cell lymphoma:
      an open clinical study and pooled data analysis.
AB  - PURPOSE: Cutaneous T-cell lymphomas (CTCLs) are dominated by mycosis fungoides
      (MF) and Sezary syndrome (SS), and durable disease control is a therapeutic
      challenge. Standard total skin electron beam therapy (TSEBT) is an effective skin
      directed therapy, but the possibility of retreatments is limited to 2 to 3
      courses in a lifetime due to skin toxicity. This study aimed to determine the
      clinical effect of low-dose TSEBT in patients with MF and SS. METHODS AND
      MATERIALS: In an open clinical study, 21 patients with MF/SS stages IB to IV were
      treated with low-dose TSEBT over <2.5 weeks, receiving a total dose of 10 Gy in
      10 fractions. Data from 10 of these patients were published previously but were
      included in the current pooled data analysis. Outcome measures were response
      rate, duration of response, and toxicity. RESULTS: The overall response rate was
      95% with a complete cutaneous response or a very good partial response rate (<1%
      skin involvement with patches or plaques) documented in 57% of the patients.
      Median duration of overall cutaneous response was 174 days (5.8 months; range: 60
      675 days). TSEBT-related acute adverse events (grade 1 or 2) were observed in 60%
      of patients. CONCLUSIONS: Low-dose (10-Gy) TSEBT offers a high overall response
      rate and is relatively safe. With this approach, reirradiation at times of
      relapse or progression is likely to be less toxic than standard dose TSEBT. It
      remains to be established whether adjuvant and combination treatments can prolong
      the beneficial effects of low-dose TSEBT.

PMID- 25863762
TI  - Simple method to estimate mean heart dose from Hodgkin lymphoma radiation therapy
      according to simulation X-rays.
AB  - PURPOSE: To describe a new method to estimate the mean heart dose for Hodgkin
      lymphoma patients treated several decades ago, using delineation of the heart on
      radiation therapy simulation X-rays. Mean heart dose is an important predictor
      for late cardiovascular complications after Hodgkin lymphoma (HL) treatment. For
      patients treated before the era of computed tomography (CT)-based radiotherapy
      planning, retrospective estimation of radiation dose to the heart can be labor
      intensive. METHODS AND MATERIALS: Patients for whom cardiac radiation doses had
      previously been estimated by reconstruction of individual treatments on
      representative CT data sets were selected at random from a case-control study of
      5-year Hodgkin lymphoma survivors (n=289). For 42 patients, cardiac contours were
      outlined on each patient's simulation X-ray by 4 different raters, and the mean
      heart dose was estimated as the percentage of the cardiac contour within the
      radiation field multiplied by the prescribed mediastinal dose and divided by a
      correction factor obtained by comparison with individual CT-based dosimetry.
      RESULTS: According to the simulation X-ray method, the medians of the mean heart
      doses obtained from the cardiac contours outlined by the 4 raters were 30 Gy, 30
      Gy, 31 Gy, and 31 Gy, respectively, following prescribed mediastinal doses of 25
      42 Gy. The absolute-agreement intraclass correlation coefficient was 0.93 (95%
      confidence interval 0.85-0.97), indicating excellent agreement. Mean heart dose
      was 30.4 Gy with the simulation X-ray method, versus 30.2 Gy with the
      representative CT-based dosimetry, and the between-method absolute-agreement
      intraclass correlation coefficient was 0.87 (95% confidence interval 0.80-0.95),
      indicating good agreement between the two methods. CONCLUSION: Estimating mean
      heart dose from radiation therapy simulation X-rays is reproducible and fast,
      takes individual anatomy into account, and yields results comparable to the labor
      intensive representative CT-based method. This simpler method may produce a
      meaningful measure of mean heart dose for use in studies of late cardiac
      complications.

PMID- 25863763
TI  - Optimized volumetric modulated arc therapy versus 3D-CRT for early stage
      mediastinal Hodgkin lymphoma without axillary involvement: a comparison of second
      cancers and heart disease risk.
AB  - PURPOSE: The purpose of this study was to evaluate the risks of second cancers
      and cardiovascular diseases associated with an optimized volumetric modulated arc
      therapy (VMAT) planning solution in a selected cohort of stage I/II Hodgkin
      lymphoma (HL) patients treated with either involved-node or involved-site
      radiation therapy in comparison with 3-dimensional conformal radiation therapy
      (3D-CRT). METHODS AND MATERIALS: Thirty-eight patients (13 males and 25 females)
      were included. Disease extent was mediastinum alone (n=8, 21.1%); mediastinum
      plus unilateral neck (n=19, 50%); mediastinum plus bilateral neck (n=11, 29.9%).
      Prescription dose was 30 Gy in 2-Gy fractions. Only 5 patients had mediastinal
      bulky disease at diagnosis (13.1%). Anteroposterior 3D-CRT was compared with a
      multiarc optimized VMAT solution. Lung, breast, and thyroid cancer risks were
      estimated by calculating a lifetime attributable risk (LAR), with a LAR ratio
      (LAR(VMAT)-to-LAR(3D-CRT)) as a comparative measure. Cardiac toxicity risks were
      estimated by calculating absolute excess risk (AER). RESULTS: The LAR ratio
      favored 3D-CRT for lung cancer induction risk in mediastinal alone (P=.004) and
      mediastinal plus unilateral neck (P=.02) presentations. LAR ratio for breast
      cancer was lower for VMAT in mediastinal plus bilateral neck presentations
      (P=.02), without differences for other sites. For thyroid cancer, no significant
      differences were observed, regardless of anatomical presentation. A significantly
      lower AER of cardiac (P=.038) and valvular diseases (P<.0001) was observed for
      VMAT regardless of disease extent. CONCLUSIONS: In a cohort of patients with
      favorable characteristics in terms of disease extent at diagnosis (large
      prevalence of nonbulky presentations without axillary involvement), optimized
      VMAT reduced heart disease risk with comparable risks of thyroid and breast
      cancer, with an increase in lung cancer induction probability. The results are
      however strongly influenced by the different anatomical presentations, supporting
      an individualized approach.

PMID- 25863765
TI  - Valorization of electric arc furnace primary steelmaking slags for cement
      applications.
AB  - To produce supplementary cementitious materials from electric arc furnace (EAF)
      slags, FeO was reduced using a two-stage reduction process that included an Al
      dross reduction reaction followed by direct carbon reduction. A decrease in FeO
      was observed on tapping after the first-stage reduction, and further reduction
      with a stirred carbon rod in the second-stage reduction resulted in final FeO
      content below 5wt%, which is compatible with cement clinker applications. The
      reduced electric arc furnace slags (REAFS) mixed with cement at a unit ratio
      exhibited physical properties comparable to those of commercialized ground
      granulated blast furnace slags (GGBFS). Confocal laser scanning microscopy (CLSM)
      was used to obtain fundamental information on the cooling characteristics and
      conditions required to obtain amorphous REAFS. REAFS can be applied in cement
      mixtures to achieve the hydraulic properties needed for commercial use. 

PMID- 25863766
TI  - The decay of wood in landfills in contrasting climates in Australia.
AB  - Wood products in landfill are commonly assumed to decay within several decades,
      returning the carbon contained therein to the atmosphere, with about half the
      carbon released as methane. However, the rate and extent of decay is not well
      known, as very few studies have examined the decay of wood products in landfills.
      This study reports on the findings from landfill excavations conducted in the
      Australian cities of Sydney and Cairns located in temperate and tropical
      environments, respectively. The objective of this study was to determine whether
      burial of the wood in warmer, more tropical conditions in Cairns would result in
      greater levels of decay than occurs in the temperate environment of Sydney. Wood
      samples recovered after 16-44years in landfill were examined through physical,
      chemical and microscopic analyses, and compared with control samples to determine
      the carbon loss. There was typically little or no decay in the wood samples
      analysed from the landfill in Sydney. Although there was significant decay in
      rainforest wood species excavated from Cairns, decay levels for wood types that
      were common to both Cairns and Sydney landfills were similar. The current
      Intergovernmental Panel on Climate Change (IPCC, 2006) default decay factor for
      organic materials in landfills is 50%. In contrast, the carbon loss determined
      for Pinus radiata recovered from Sydney and Cairns landfills was 7.9% and 4.4%,
      respectively, and 0% for Agathis sp. This suggests that climate did not influence
      decay, and that the more extensive levels of decay observed for some wood samples
      from Cairns indicates that those wood types were more susceptible to
      biodegradation. Microscopic analyses revealed that most decay patterns observed
      in samples analysed from Sydney were consistent with aerobic fungal decay. Only a
      minor portion of the microbial decay was due to erosion bacteria active in
      anaerobic/near anaerobic environments. The findings of this study strongly
      suggest that models that adopt current accepted default factors for the decay of
      wood in landfills greatly overestimate methane emissions. 

PMID- 25863764
TI  - Predictors of radiation pneumonitis in patients receiving intensity modulated
      radiation therapy for Hodgkin and non-Hodgkin lymphoma.
AB  - PURPOSE: Few studies to date have evaluated factors associated with the
      development of radiation pneumonitis (RP) in patients with Hodgkin lymphoma (HL)
      and non-Hodgkin lymphoma (NHL), especially in patients treated with contemporary
      radiation techniques. These patients represent a unique group owing to the often
      large radiation target volumes within the mediastinum and to the potential to
      receive several lines of chemotherapy that add to pulmonary toxicity for relapsed
      or refractory disease. Our objective was to determine the incidence and clinical
      and dosimetric risk factors associated with RP in lymphoma patients treated with
      intensity modulated radiation therapy (IMRT) at a single institution. METHODS AND
      MATERIALS: We retrospectively reviewed clinical charts and radiation records of
      150 consecutive patients who received mediastinal IMRT for HL and NHL from 2009
      through 2013. Clinical and dosimetric predictors associated with RP according to
      Radiation Therapy Oncology Group (RTOG) acute toxicity criteria were identified
      in univariate analysis using the Pearson chi(2) test and logistic multivariate
      regression. RESULTS: Mediastinal radiation was administered as consolidation
      therapy in 110 patients with newly diagnosed HL or NHL and in 40 patients with
      relapsed or refractory disease. The overall incidence of RP (RTOG grades 1-3) was
      14% in the entire cohort. Risk of RP was increased for patients who received
      radiation for relapsed or refractory disease (25%) versus those who received
      consolidation therapy (10%, P=.019). Several dosimetric parameters predicted RP,
      including mean lung dose of >13.5 Gy, V20 of >30%, V15 of >35%, V10 of >40%, and
      V5 of >55%. The likelihood ratio chi(2) value was highest for V5 >55% (chi(2) =
      19.37). CONCLUSIONS: In using IMRT to treat mediastinal lymphoma, all dosimetric
      parameters predicted RP, although small doses to large volumes of lung had the
      greatest influence. Patients with relapsed or refractory lymphoma who received
      salvage chemotherapy and hematopoietic stem cell transplantation were at higher
      risk for symptomatic RP.

PMID- 25863767
TI  - Effectiveness of the food recovery at the retailing stage under shelf life
      uncertainty: An application to Italian food chains.
AB  - Food losses represent a significant issue affecting food supply chains. The
      possibility of recovering such products can be seen as an effective way to reduce
      such a phenomenon, improve supply chain performances and ameliorate the
      conditions of undernourished people. The topic has been already investigated by a
      previous paper enforcing the hypothesis of deterministic and constant Shelf Life
      (SL) of products. However, such a model cannot be properly extended to products
      affected by uncertainties of the SL as it does not take into account the
      deterioration costs and loss of profits due to the overcoming of the SL within
      the cycle time. Thus the present paper presents an extension of the previous one
      under stochastic conditions of the food quality. Differently from the previous
      publication, this work represents a general model applicable to all supply
      chains, especially to those managing fresh products characterized by uncertain SL
      such as fruits and vegetables. The deterioration costs and loss of profits are
      included in the model and the optimal time at which to withdraw the products from
      the shelves as well as the quantities to be shipped at each alternative
      destination have been determined. A comparison of the proposed model with that
      reported in the previous publication has been carried out in order to underline
      the impact of the SL variability on the optimality conditions. The results show
      that the food recovery strategy in the presence of uncertainty of the food
      quality is rewarding, even if the optimal profit is lower than that of the
      deterministic case. 

PMID- 25863768
TI  - An investigation into between-meal food desires among hospitalised haematological
      cancer patients.
AB  - BACKGROUND & AIMS: Hospitalised haematological cancer patients often suffer from
      reduced appetite and food intake, which negatively influences the patients' well
      being and nutritional status. The aim of this study was to identify specific
      between-meal food desires in a patient group, in order to increase food intake.
      The study was conducted using a picture-aided questionnaire, and relating the
      preferences to factors that could easily be implemented in the hospital menu,
      such as time of the day and texture. Moreover, the results of the questionnaire
      were verified by acceptance tests on six selected food items. METHODS: A
      structured 42 items food questionnaire was developed and used to quantify
      appetitive food desires in patients during morning (11 am) and afternoon (3 pm)
      sessions. Food items were scored according to patients' preferences and immediate
      desire to eat. A total of 112 hospitalised haematological cancer patients,
      screened for nutrition-related symptoms, participated. Univariate statistical
      models were used to investigate the influence of time-of-day and food texture on
      between-meal desires. RESULTS: Fresh fruit, ice cream, cheese and mashed potatoes
      with bacon were the most desired food items. Patients showed significant higher
      desire to eat in the morning as opposed to the afternoon. Moreover, texture had
      an influence on food desire, where liquid food was more desired than food with
      soft or coarse texture. CONCLUSION: Ranking of food desires among hospitalised
      cancer patients showed inclination for fresh fruit, ice cream, mashed potatoes
      with bacon, and cheese. Time of the day (morning) and texture (liquid) had the
      greatest and most positive impact on food desires. The findings may be easily
      implemented in hospital food service routines for cancer patients, and might
      positively contribute to patients' well-being and nutrition.

PMID- 25863769
TI  - High dietary acid load is associated with insulin resistance: The Furukawa
      Nutrition and Health Study.
AB  - BACKGROUND & AIMS: Acid-base imbalance has been suggested to play an important
      role in certain cardio-metabolic abnormalities, including type 2 diabetes;
      however, epidemiological evidence linking dietary acid load to glucose metabolism
      is lacking. We examined the association of dietary acid load with markers of
      insulin resistance (IR), insulin secretion, and blood glucose status among
      Japanese workers. METHODS: The study subjects were 1732 workers, aged 19-69
      years, who completed a health survey at a periodic checkup. Dietary intake was
      assessed using a validated brief diet history questionnaire. Potential renal acid
      load (PRAL) and net endogenous acid production (NEAP) scores were derived from
      nutrient intake. A multilevel linear regression model was used to estimate the
      means of fasting insulin, fasting plasma glucose, homeostatic model assessment of
      IR (HOMA-IR) score, homeostatic model assessment of beta-cell function (HOMA
      beta) score and glycated hemoglobin (HbA1c) level with adjustment for potential
      confounding variables. RESULTS: PRAL was positively associated with HOMA-IR score
      (Ptrend = 0.045); the multivariable-adjusted means (95% confidence intervals) for
      the HOMA-IR scores for the lowest through the highest quartiles of PRAL were 0.88
      (0.82-0.94), 0.92 (0.86-0.98), 0.92 (0.86-0.98), and 0.94 (0.88-1.01). A similar
      association was observed between NEAP and HOMA-IR scores (Ptrend = 0.03). In the
      stratified analyses, these positive associations were confined to subjects with
      lower BMIs (<23 kg/m(2)) (Ptrend = 0.03 and 0.01 for PRAL and NEAP,
      respectively). NEAP score was positively associated with HOMA-beta score (Ptrend
      = 0.03). Dietary acid load score was not appreciably associated with fasting
      glucose or HbA1c levels. CONCLUSIONS: The present findings suggest that high
      dietary acid load is associated with IR among apparently healthy adults.

PMID- 25863771
TI  - A case of appendicitis with appendicolith diagnosed with ultrasound in the
      emergency department.

PMID- 25863770
TI  - The factors associated with self-reported physical activity in older adults
      living in the community.
AB  - BACKGROUND: despite the vast literature in the area, few studies examined the
      large range of factors associated with physical activity (PA) in the older adult
      collectively, information that could help develop a supportive culture for
      healthy ageing. OBJECTIVE: to identify the socio-demographic, social
      connectedness, physical environment and physical and mental health-related
      factors associated with PA. SETTING AND PARTICIPANTS: adults aged 65 and over
      living in the community (n = 3499). METHODS: this study used a cross-sectional
      design. Self-report, interview and physical assessment were the data collection
      methods used. The International Physical Activity Questionnaire (short form)
      measured PA in metabolic equivalents. RESULTS: 31.8% of older people did not meet
      the recommended guidelines. The regression model was significant, explaining
      31.3% of the variance in PA (F = 34.32, P < 0.001). In order of strength of
      relationship, the beta coefficients, the variables time spent sitting, gender,
      quality of life, grip test, disability, age, depression, BMI, anxiety,
      employment, member of a non-church club, type of house and cognitive ability were
      significant factors associated with PA. CONCLUSION: from a range of 40 original
      variables, this study identified the variables most strongly related to PA were
      not physical health or physical environment. They included modifiable variables,
      such as time spent sitting and mental health, which can be actively targeted in
      policy and practice. They also included non-modifiable variables such as gender
      and age that can be addressed through increased awareness and targeted health
      promotion.

PMID- 25863772
TI  - Emergency Evaluation for Pulmonary Embolism, Part 1: Clinical Factors that
      Increase Risk.
AB  - BACKGROUND: Pulmonary embolism (PE) can be fatal, but profligate testing for PE
      can harm patients. OBJECTIVES: With consideration of potential medicolegal
      implications, this two-part review provides current evidence about the care of
      patients with suspected and diagnosed PE in the emergency department (ED)
      setting. DISCUSSION: In part 1, we review published evidence to describe the
      epidemiology, risk factors, and clinical presentation of PE in the ED setting.
      Older age, surgery requiring endotracheal intubation within the past 30 days, new
      use of oral contraceptives, and prior unprovoked venous thromboembolism in
      nonanticoagulated patients are clear risk factors for PE in ED patients. Recent
      history of unexplained dyspnea, pleuritic chest pain, and hemoptysis increase
      probability, but the effect of syncope is less clear. Treated and inactive
      cancer, smoking, obesity, and pregnancy have not been found to increase the
      probability of PE in symptomatic ED patients. Unexplained dyspnea, tachycardia,
      and a low pulse oximetry reading increase probability of PE. Finding of wheezing
      on lung auscultation reduces the probability of PE, and findings that suggest
      deep venous thrombosis increase the probability of PE. CONCLUSIONS: Understanding
      of risk factors, historical data, and physical findings that have been found to
      increase or decrease the probability of PE in symptomatic ED patients can help
      create rational guidelines for the diagnostic approach to PE.

PMID- 25863773
TI  - Physico-chemical analysis of ground water samples of coastal areas of south
      Chennai in the post-Tsunami scenario.
AB  - The study of changes in ground water quality on the east coast of chennai due to
      the December 26, 2004 tsunami and other subsequent disturbances is a matter of
      great concern. The post-Tsunami has caused considerable plant, animal, material
      and ecological changes in the entire stretch of chennai coastal area. Being very
      close to sea and frequently subjected to coastal erosion, water quality has been
      a concern in this coastal strip, and especially after the recent tsunami this
      strip seems to be more vulnerable. In the present investigation, ten ground water
      samples were collected from various parts of south chennai coastal area. Physico
      chemical parameters such as pH, temperature, Biochemical oxygen demand (BOD),
      Dissolved oxygen (DO), total solids; turbidity and fecal coliform were analyzed.
      The overall Water quality index (WQI) values for all the samples were found to be
      in the range of 68.81-74.38 which reveals a fact that the quality of all the
      samples is only medium to good and could be used for drinking and other domestic
      uses only after proper treatment. The long term adverse impacts of tsunami on
      ground water quality of coastal areas and the relationships that exist and among
      various parameters are carefully analyzed. Local residents and corporation
      authorities have been made aware of the quality of their drinking water and the
      methods to conserve the water bodies. 

PMID- 25863774
TI  - Maternal Depressive Symptomatology, Social Support, and Language Development of
      Bilingual Preschoolers From Low-Income Households.
AB  - PURPOSE: This study examined the impact of maternal depressive symptomatology and
      social support on the English and Spanish language growth of young bilingual
      children from low-income backgrounds. It was hypothesized that maternal
      depression would slow children's development in both languages but that social
      support would buffer the negative effect. METHOD: Longitudinal data were
      collected from 83 mothers of Puerto Rican descent and their children who were
      attending Head Start preschool for 2 years. The effects of maternal depressive
      symptomatology and social support from family and friends on receptive vocabulary
      and oral comprehension development in both languages were examined. RESULTS:
      Growth curve modeling revealed that maternal depressive symptomatology negatively
      affected Spanish receptive vocabulary development only. Maternal depression did
      not affect children's English receptive vocabulary or their oral comprehension in
      either language. Social support was not related to maternal depressive
      symptomatology or child language. CONCLUSIONS: These findings suggest that
      maternal depression is 1 risk factor that contributes to less robust primary
      language development of bilingual children from low-income households. Speech
      language pathologists must (a) increase their awareness of maternal depression in
      order to provide families with appropriate mental health referrals and (b)
      consider their roles as supportive adults for children whose mothers may be
      depressed.

PMID- 25863775
TI  - Mechanisms that lead to the regulation of NLRP3 inflammasome expression and
      activation in human dental pulp fibroblasts.
AB  - BACKGROUND: The NLRP3 inflammasome plays an important role in the cellular
      defense against invading pathogens and is reported to be expressed in human
      dental pulp fibroblasts (HDPFs). However, the role of the NLRP3 inflammasome in
      HDPFs during pulpal infection and inflammation remains unclear. OBJECTIVES: To
      elucidate the function of the NLRP3 inflammasome and the mechanisms that lead to
      its expression and activation in HDPFs. METHODS: The test model used
      lipopolysaccharide (LPS) and adenosine triphosphate (ATP) to simulate an
      inflammatory environment. Lentiviral vectors encoding short hairpin RNAs were
      used to knock down NLRP3 and caspase-1 in HDPFs. Specific inhibitors were used to
      determine whether the toll-like receptor 4 (TLR4), myeloid differentiating factor
      88 (MyD88), or nuclear factor-kappa B (NF-kappaB) pathways were involved in the
      regulation of NLRP3 expression. Reactive oxygen species (ROS) production was
      measured by fluorescent microscopy and flow cytometry using the total
      ROS/superoxide detection kit. Gene and protein expression were quantified by real
      time polymerase chain reaction and Western blot, while cytokine release was
      measured by an enzyme-linked immunosorbent assay. RESULTS: LPS up-regulated NLRP3
      and IL-1beta expression while ATP induced the activation of caspase-1 and the
      release of IL-1beta in LPS-primed HDPFs. The knockdown of NLRP3 or caspase-1
      expression significantly inhibited IL-1beta secretion. Pretreatment with a TLR4
      inhibitor, a MyD88 inhibitory peptide, or an I Kappa B alpha (IkappaBalpha)
      phosphorylation inhibitor significantly inhibited LPS-induced NLRP3 and IL-1beta
      expression. ATP potently promoted ROS generation in HDPFs; N-acetyl cysteine
      inhibited ROS production, caspase-1 activation and IL-1beta secretion induced by
      ATP. CONCLUSIONS: Our results demonstrated that the NLRP3 inflammasome in HDPFs
      is crucial for IL-1beta secretion in response to LPS plus ATP. LPS engaged the
      TLR4/MyD88/NF-kappaB pathway to enhance NLRP3 and pro-IL-1beta expression in
      HDPFs. ATP promoted the generation of ROS and activated the NLRP3 inflammasome in
      a ROS-dependent manner.

PMID- 25863776
TI  - Double trouble: T2DM genetic risk factors play a causal role in CAD.

PMID- 25863777
TI  - Cardiovascular and autoimmune diseases in females: The role of microvasculature
      and dysfunctional endothelium.
AB  - Cardiovascular (CV) diseases are becoming increasingly frequent and associated
      with a high incidence of CV events, disability and death. It is known that there
      is a relationship between CV burden and systemic autoimmune diseases (SADs) that
      is mainly due to inflammation and autoimmunity, but the other mechanisms
      underlying the high CV risk of SAD patients have not yet been fully clarified.
      The aim of this review article is to discuss some of the specific factors
      associated with the accelerated atherosclerosis (ATS) characterising SADs (female
      sex, the microcirculation and the endothelium) in order to highlight the
      importance of an early diagnosis and the prompt implementation of preventive
      measures, as well as the possible role of new therapeutic strategies such as
      vaccine immunomodulation. Finally, as the natural history of ATS begins with
      endothelial injury (a potentially reversible process that is influenced by
      various factors) and microvascular damage plays a central role in the
      etiopathogenesis of SADs, it underlines the crucial need for the development of
      reliable means of detecting sub-clinical abnormalities in the microcirculation,
      particularly coronary microcirculation dysfunction. 

PMID- 25863778
TI  - Long-term follow-up of immunotherapy-unresponsive recurrent tumefactive
      demyelination.

PMID- 25863779
TI  - Activity of MMP1 and MMP13 and amino acid metabolism in patients with alcoholic
      liver cirrhosis.
AB  - BACKGROUND: Alcoholic liver disease remains one of the most common causes of
      chronic liver disease worldwide. The aim of this study was to assess the
      usefulness of metalloproteinases (MMP1 and MMP13) as diagnostic markers of
      alcoholic liver disease and to determine the changes in free amino acid profile
      in the patients with alcoholic liver cirrhosis. MATERIAL AND METHODS: Sixty
      patients with alcoholic liver cirrhosis treated in various hospitals of the
      Lublin region were randomly enrolled. The control group consisted of 10 healthy
      individuals without liver disease, who did not drink alcohol. Additionally, a
      group of alcoholics (22 persons) without liver cirrhosis was included in the
      study. The activity of MMP-1 and MMP-13 in blood plasma of patients and controls
      was measured using the sandwich enzyme immunoassay technique with commercially
      available quantitative ELISA test kits. Amino acids were determined by automated
      ion-exchange chromatography. RESULTS: No significant differences were observed in
      the activity of MMP-1 in alcoholics with or without liver cirrhosis or in
      controls. Increased serum MMP-13 was found in patients with liver cirrhosis
      (stage A, B, C) compared to the control group. Patients with alcoholic liver
      cirrhosis (stage A, B, C) demonstrated reduced concentrations of glutamic acid
      and glutamine compared to the control group. Plasma levels of valine, isoleucine,
      leucine, and tryptophan were significantly lower in patients with alcoholic liver
      cirrhosis (stage C) than in controls. CONCLUSIONS: MMP-13 can be useful to
      confirm the diagnosis of alcoholic liver cirrhosis, but levels of MMP-1 are not
      significantly increased in patients with liver cirrhosis compared to controls.
      The serum branched-chain amino acid (BCAA) is markedly reduced in patients with
      stage C alcoholic liver cirrhosis.

PMID- 25863780
TI  - Serum TRAIL levels increase shortly after insulin therapy and metabolic
      stabilization in children with type 1 diabetes mellitus.

PMID- 25863781
TI  - Screening of glucose metabolism derangements in pediatric cystic fibrosis
      patients: how, when, why.
AB  - Diabetes mellitus is the most common comorbidity in cystic fibrosis (CF),
      occurring in a variable number of children and adolescents. Glucose metabolism
      derangements (GMDs) are responsible for a negative impact on the general health
      status of CF patients. Screening of GMDs is important since the youngest age and
      should be performed by means of OGTT, including its intermediate times, that
      could detect other non-traditional GMDs. Insulin treatment, administered before
      overt diabetes, could be beneficial in reducing the number of pulmonary
      infections, in improving both pulmonary function and nutritional status. Early
      screening of GMDs in pediatric age can exert an important preventing role
      regarding all aspects of health status of patients with CF.

PMID- 25863782
TI  - Reducing the risk of metabolic syndrome at the worksite: preliminary experience
      with an ecological approach.
AB  - AIM: Given the time spent at work, the workplace represents an ideal setting to
      implement preventive programs for non-communicable diseases, the major cause of
      mortality and morbidity in Western and developing countries. We sought to verify
      if an ecological approach based on corporate culture, employees' education and
      concrete modifications of workplace environment, offering easy opportunity to
      assume healthy lifestyle, could be associated with reduced cardiometabolic risk.
      METHODS: The study involved 1089 workers in two multinational companies following
      different workplace health promotion policies. Company A offered to all employees
      the opportunity to access a web platform dedicated to general information on
      health and diseases. Company B implemented an ecological model encompassing
      company culture, employees' education and concrete modifications of workplace
      environment, giving to all employees the opportunity to adopt healthy solutions
      throughout daily living at workplace. Participants volunteered self-reported
      clinical information using an IT tool. Numbers of Metabolic Syndrome components
      (MetS) were taken as proxy of cardiometabolic risk. RESULTS: MetS probability
      obtained via statistical modeling was lower in company B as compared to company
      A, and absenteeism was also lower in company B. Our study shows that a work
      environment favoring assumption of healthy lifestyle, as in company B, is
      associated with a lower percentage of employees with MetS components and lower
      absenteeism. Moreover, statistical modeling shows that individual probabilities
      of being without MetS elements, controlling for age and gender, is remarkably
      higher in company B. CONCLUSIONS: Our data suggest that ecological approaches
      might be useful in worksite prevention policies.

PMID- 25863783
TI  - Expanding the Utility of FUCCI Reporters Using FACS-Based Omics Analysis.
AB  - The FUCCI indicator system is a powerful tool for spatio-temporal analysis of the
      cell cycle, but its utility has been restricted so far to a limited range of
      applications. Here, we describe how to establish and validate the FUCCI system in
      murine pluripotent stem cells (PSCs) and describe the utility of transgenic FUCCI
      mice. We then describe how the FUCCI system can be used to generate material for
      a wide-range of omics-based applications in conjunction with FACS isolation of
      cells. This significantly broadens the potential applications of FUCCI reporters
      for studying the molecular basis of development and disease.

PMID- 25863784
TI  - Methods for Ex Vivo Analysis of Immune Cell Function from the Central Nervous
      System.
AB  - Experimental autoimmune encephalomyelitis (EAE) is an animal model commonly used
      to investigate the inflammatory response in organ-specific autoimmunity and a
      model of the early immune responses of multiple sclerosis.This protocol outlines
      the methods used for the processing of peripheral immune tissues, the spleen and
      draining lymph nodes, as well as the site of inflammation, the central nervous
      system (CNS), for analyzing immune cell phenotype and function during murine EAE.

PMID- 25863785
TI  - Derivation of Neural Stem Cells from Mouse Induced Pluripotent Stem Cells.
AB  - Neural stem cells (NSCs) derived from induced pluripotent stem cells offer
      therapeutic tools for neurodegenerative diseases. This review focuses on embryoid
      body (EB)-mediated stem cell culture techniques used to derive NSCs from mouse
      induced pluripotent stem cells (iPSCs). Generation of healthy and stable NSCs
      from iPSCs heavily depends on standardized in vitro cell culture systems that
      mimic the embryonic environments utilized during neural development.
      Specifically, the neural induction and expansion methods after EB formation are
      described in this review. 

PMID- 25863786
TI  - Maintenance, Transgene Delivery, and Pluripotency Measurement of Mouse Embryonic
      Stem Cells.
AB  - This chapter describes standard techniques to (1) maintain mouse embryonic stem
      cell culture, (2) deliver transgenes into mouse embryonic stem cells mediated by
      electroporation, nucleofection, lipofection, and retro/lentiviruses, and (3)
      assess the pluripotency of mouse embryonic stem cells. The last part of this
      chapter presents induction of random cell differentiation followed by the
      alkaline phosphatase and embryoid body formation assays, immunofluorescence
      microscopy, and the teratoma formation assay.

PMID- 25863787
TI  - Bioinformatics and Microarray Data Analysis on the Cloud.
AB  - High-throughput platforms such as microarray, mass spectrometry, and next
      generation sequencing are producing an increasing volume of omics data that needs
      large data storage and computing power. Cloud computing offers massive scalable
      computing and storage, data sharing, on-demand anytime and anywhere access to
      resources and applications, and thus, it may represent the key technology for
      facing those issues. In fact, in the recent years it has been adopted for the
      deployment of different bioinformatics solutions and services both in academia
      and in the industry. Although this, cloud computing presents several issues
      regarding the security and privacy of data, that are particularly important when
      analyzing patients data, such as in personalized medicine. This chapter reviews
      main academic and industrial cloud-based bioinformatics solutions; with a special
      focus on microarray data analysis solutions and underlines main issues and
      problems related to the use of such platforms for the storage and analysis of
      patients data. 

PMID- 25863788
TI  - cGMP-Compliant Expansion of Human iPSC Cultures as Adherent Monolayers.
AB  - Therapeutic uses of cells differentiated from human pluripotent stem cells
      (hPSCs), either embryonic stem (ES) cells or induced pluripotent stem cells
      (iPSCs), are now being tested in clinical trials, and it is likely that this will
      lead to increased commercial interest in the clinical translation of promising
      hPSC research. Recent technical advances in the use of defined media and culture
      substrates have significantly improved both the simplicity and predictability of
      growing hPSCs, allowing a much more straightforward application of current good
      manufacturing practices (cGMP) to the culture of these cells. In addition, the
      adoption of cGMP-compliant techniques in research environments will both improve
      the replication of results and make the transition of promising investigations to
      the commercial sector significantly less cumbersome. However, passaging methods
      for hPSCs are inherently unpredictable and rely on operator experience and
      expertise. This is problematic for the cell manufacturing process where operator
      time and process predictability are often determining cost drivers. We have
      adopted a human iPSC system using defined media and a recombinant substrate that
      employs cell dissociation with a hypertonic citrate solution which eliminates
      variability during hPSC cell expansion and provides a simple cGMP-compliant
      technique for hiPSC cultivation that is appropriate in both research and
      commercial applications.

PMID- 25863789
TI  - Evaluation of selected acaricides against twospotted spider mite (Acari:
      Tetranychidae) on greenhouse cotton using multispectral data.
AB  - Twospotted spider mite (TSSM), Tetranychus urticae Koch, is an early season pest
      of cotton in the mid-southern USA and causes reduction in yield, fiber quality
      and impaired seed germination. Objectives of this study were to investigate the
      efficacy of abamectin and spiromesifen with two divergent LC50 values against
      TSSM in a computer-operated spray table which simulated aerial application
      parameters. Combined with a pressure of 276 kPa and a speed of 8 km/h, a 650033
      nozzle delivered a spray rate of 18.7 L/ha. The active ingredient rates were 1/8,
      1/4, 1/2 and the lowest label recommended rates for early season cotton. The
      intent was to study efficacy relative to deposition characteristics at active
      ingredient rates equal to and lower than those recommended by the label. Spectral
      reflectance values from a multispectral optical sensor were used to calculate the
      Normalized Difference Vegetation Index which numerically described the surface
      reflectance characteristics of cotton canopies concomitant to damage caused by T.
      urticae in the greenhouse. Water sensitive paper samplers described spray droplet
      spectra parameters (Dv0.1, Dv0.5 and Dv0.9, um) and percent spray coverage. The
      volume median diameter (Dv0.5, um) for abamectin and spiromesifen were
      respectively, 218 and 258 at one-half rate of the lowest label rate. These spray
      droplets were well above the driftable portions of the spray volume (<141 um) for
      both abamectin and spiromesifen. Efficacy evaluations indicated that spiromesifen
      was more effective than abamectin in controlling T. urticae on early season
      cotton at one-half rate of the lowest label rate. Results reported herein
      demonstrate that the multispectral optical sensor in lieu of manually counting T.
      urticae appears to be a promising tool for efficacy evaluations against
      acaricides for early season plants grown in greenhouses. 

PMID- 25863790
TI  - Dealing with Disobedience: An Evaluation of a Brief Parenting Intervention for
      Young Children Showing Noncompliant Behavior Problems.
AB  - The study was a randomized controlled trial evaluating the efficacy of a brief
      and preventatively-focused parenting discussion group for dealing with
      disobedient behavior in preschool-aged children. Eighty-five parents with
      children aged between 3 and 5 years who were concerned about the noncompliant
      behavior of their child were recruited from Auckland, New Zealand and Brisbane,
      Australia. Compared to the waitlist control group (n = 40), parents in the
      intervention group (n = 45) reported greater improvements in disruptive child
      behavior, ineffective parenting practices and parenting confidence, as well as
      clinically significant improvements in child behavior and parenting. All of these
      effects were maintained at 6-month follow up. No group differences were found for
      parental wellbeing, inter-parental conflict and general relationship quality,
      although intervention parents reported improvements in parental wellbeing and
      inter-parental conflict at 6-month follow-up. The findings are discussed in terms
      of the implications for making brief and effective parenting support available to
      parents. 

PMID- 25863791
TI  - Spontaneous eye blinks during creative task correlate with divergent processing.
AB  - Creativity consists of divergent and convergent thinking, with both related to
      individual eye blinks at rest. To assess underlying mechanisms between eye blinks
      and traditional creativity tasks, we investigated the relationship between
      creativity performance and eye blinks at rest and during tasks. Participants
      performed an alternative uses and remote association task while eye blinks were
      recorded. Results showed that the relationship between eye blinks at rest and
      creativity performance was compatible with those of previous research.
      Interestingly, we found that the generation of ideas increased as a function of
      eye blink number during the alternative uses task. On the other hand, during the
      remote association task, accuracy was independent of eye blink number during the
      task, but response time increased with it. Moreover, eye blink changes in
      participants who responded quickly during the remote association task were
      different depending on their resting state eye blinks; that is, participants with
      many eye blinks during rest showed little increasing eye blinks and achieved
      solutions quickly. Positive correlations between eye blinks during creative tasks
      and yielding ideas on the alternative uses task and response time on the remote
      association task suggest that eye blinks during creativity tasks relate to
      divergent thinking processes such as conceptual reorganization. 

PMID- 25863792
TI  - Radiology report turnaround time: effect on resident education.
AB  - RATIONALE AND OBJECTIVES: To compare resident workload from Emergency Department
      (ED) studies before and after the implementation of a required 1-hour report
      turnaround time (TAT) and to assess resident and faculty perception of TAT on
      resident education. MATERIALS AND METHODS: Resident study volume will be compared
      for 3 years before and 1 year after the implementation of a required 1-hour TAT.
      Changes to resident workload will be compared among the different radiology
      divisions (body, muscuolskeletal (MSK), chest, and neuro), as well as during
      different shifts (daytime and overnight). Residents and faculty at two Midwest
      institutions, both of which have a required report TAT, will be invited to
      participate in an online survey to query the perceived effect on resident
      education by implementation of this requirement. A P < .05 was considered
      statistically significant. RESULTS: A significant decrease in resident
      involvement in ED studies was noted in the MSK, chest, and neuro sections with
      average involvement of the 3 years before the 1-hour TAT of 89%, 88%, and 82%,
      respectively, which decreased to 66%, 68%, and 51% after the 1-hour TAT
      requirement (P < .05). The resident involvement in ED studies only mildly
      decreased in the body section from an average before the 1-hour TAT of 87% to 80%
      after the 1-hour TAT requirement (P < .1). There was an overall significant
      decrease in resident ED study involvement during the daytime (P = .01) but not
      after hours during resident call (P = .1). Seventy percent of residents (43 of
      61) and 55% of faculty (63 of 114) responded to our surveys. Overall, residents
      felt their education from ED studies during the daytime and overnight were good.
      However, residents who were present both before and after the implementation of a
      required TAT felt their education had been significantly negatively affected.
      Faculty surveyed thought that the required TAT negatively affected their ability
      to teach and decreased the quality of resident education. CONCLUSIONS: Residents
      are exposed to fewer ED studies after the implementation of a required 1-hour
      TAT. Overall, the current residents do not feel this decreased exposure to
      Emergency room studies affects their education. However, residents in training
      before and after this requirement feel their education has been significantly
      affected. Faculty perceives that the required TAT negatively affects their
      ability to teach, as well as the quality of resident education.

PMID- 25863793
TI  - Simulation-based educational curriculum for fluoroscopically guided lumbar
      puncture improves operator confidence and reduces patient dose.
AB  - RATIONALE AND OBJECTIVES: Fluoroscopically guided lumbar puncture (FGLP) is a
      commonly performed procedure with increased success rates relative to bedside
      technique. However, FGLP also exposes both patient and staff to ionizing
      radiation. The purpose of this study was to determine if the use of a simulation
      based FGLP training program using an original, inexpensive lumbar spine phantom
      could improve operator confidence and efficiency, while also reducing patient
      dose. MATERIALS AND METHODS: A didactic and simulation-based FGLP curriculum was
      designed, including a 1-hour lecture and hands-on training with a lumbar spine
      phantom prototype developed at our institution. Six incoming post-graduate year 2
      (PGY-2) radiology residents completed a short survey before taking the course,
      and each resident practiced 20 simulated FGLPs using the phantom before their
      first clinical procedure. Data from the 114 lumbar punctures (LPs) performed by
      the six trained residents (prospective cohort) were compared to data from 514 LPs
      performed by 17 residents who did not receive simulation-based training
      (retrospective cohort). Fluoroscopy time (FT), FGLP success rate, and indication
      were compared. RESULTS: There was a statistically significant reduction in
      average FT for the 114 procedures performed by the prospective study cohort
      compared to the 514 procedures performed by the retrospective cohort. This held
      true for all procedures in aggregate, LPs for myelography, and all procedures
      performed for a diagnostic indication. Aggregate FT for the prospective group
      (0.87 +/- 0.68 minutes) was significantly lower compared to the retrospective
      group (1.09 +/- 0.65 minutes) and resulted in a 25% reduction in average FT (P =
      .002). There was no statistically significant difference in the number of failed
      FGLPs between the two groups. CONCLUSIONS: Our simulation-based FGLP curriculum
      resulted in improved operator confidence and reduced FT. These changes suggest
      that resident procedure efficiency was improved, whereas patient dose was
      reduced. The FGLP training program was implemented by radiology residents and
      required a minimal investment of time and resources. The LP spine phantom used
      during training was inexpensive, durable, and effective. In addition, the phantom
      is compatible with multiple modalities including fluoroscopy, computed
      tomography, and ultrasound and could be easily adapted to other applications such
      as facet injections or joint arthrograms.

PMID- 25863794
TI  - Impact of an Information Technology-Enabled Initiative on the Quality of Prostate
      Multiparametric MRI Reports.
AB  - RATIONALE AND OBJECTIVES: Assess the impact of implementing a structured report
      template and a computer-aided diagnosis (CAD) tool on the quality of prostate
      multiparametric magnetic resonance imaging (mp-MRI) reports. MATERIALS AND
      METHODS: Institutional Review Board approval was obtained for this Health
      Insurance Portability and Accountability Act-compliant study performed at an
      academic medical center. The study cohort included all prostate mp-MRI reports (n
      = 385) finalized 6 months before and after implementation of a structured report
      template and a CAD tool (collectively the information technology [IT] tools)
      integrated into the picture archiving and communication system workstation.
      Primary outcome measure was quality of prostate mp-MRI reports. An expert panel
      of our institution's subspecialty-trained abdominal radiologists defined prostate
      mp-MRI report quality as optimal, satisfactory, or unsatisfactory based on
      documentation of nine variables. Reports were reviewed to extract the predefined
      quality variables and determine whether the IT tools were used to create each
      report. Chi-square and Student's t tests were used to compare report quality
      before and after implementation of IT tools. RESULTS: The overall proportion of
      optimal or satisfactory reports increased from 29.8% (47/158) to 53.3% (121/227)
      (P < .001) after implementing the IT tools. Although the proportion of optimal or
      satisfactory reports increased among reports generated using at least one of the
      IT tools (47/158 = [29.8%] vs. 105/161 = [65.2%]; P < .001), there was no change
      in quality among reports generated without use of the IT tools (47/158 = [29.8%]
      vs. 16/66 = [24.2%]; P = .404). CONCLUSIONS: The use of a structured template and
      CAD tool improved the quality of prostate mp-MRI reports compared to free-text
      report format and subjective measurement of contrast enhancement kinetic curve.

PMID- 25863795
TI  - Multimodality 3D Tumor Segmentation in HCC Patients Treated with TACE.
AB  - RATIONALE AND OBJECTIVES: To validate the concordance of a semiautomated
      multimodality lesion segmentation technique between contrast-enhanced magnetic
      resonance imaging (CE-MRI), cone-beam computed tomography (CBCT), and
      multidetector CT (MDCT) in patients with hepatocellular carcinoma (HCC) treated
      with transarterial chemoembolization (TACE). MATERIALS AND METHODS: This
      retrospective analysis included 45 patients with unresectable HCC who underwent
      baseline CE-MRI within 1 month before the treatment, intraprocedural CBCT during
      conventional TACE, and MDCT within 24 hours after TACE. Fourteen patients were
      excluded because of atypical lesion morphology, portal vein invasion, or small
      lesion size which precluded sufficient lesion visualization. Thirty-one patients
      with a total of 40 target lesions were included into the analysis. A tumor
      segmentation software, based on non-Euclidean geometry and theory of radial basis
      functions, was used to allow for the segmentation of target lesions in 3D on all
      three modalities. The algorithm created image-based masks located in a 3D region
      whose center and size were defined by the user, yielding the nomenclature
      "semiautomatic". On the basis of that, tumor volumes on all three modalities were
      calculated and compared using a linear regression model (R(2) values). Residual
      plots were used to analyze drift and variance of the values. RESULTS: The mean
      value of tumor volumes was 18.72 +/- 19.13 cm(3) (range, 0.41-59.16 cm(3)) on CE
      MRI, 21.26 +/- 21.99 cm(3) (range, 0.62-86.82 cm(3)) on CBCT, and 19.88 +/- 20.88
      cm(3) (range, 0.45-75.24 cm(3)) on MDCT. The average volumes of the tumor were
      not significantly different between CE-MRI and DP-CBCT, DP-CBCT and MDCT, MDCT
      and CE-MRI (P = .577, .770, and .794, respectively). A strong correlation between
      volumes on CE-MRI and CBCT, CBCT and MDCT, MDCT and CE-MRI was observed (R(2) =
      0.974, 0.992 and 0.983, respectively). When plotting the residuals, no drift was
      observed for all methods showing deviations of no >10% of absolute volumes (in
      cm(3)). CONCLUSIONS: A semiautomated 3D segmentation of HCC lesions treated with
      TACE provides high volumetric concordance across all tested imaging modalities.

PMID- 25863796
TI  - Reflective Practice: Assessing Its Effectiveness to Teach Professionalism in a
      Radiology Residency.
AB  - RATIONALE AND OBJECTIVES: Professionalism can be challenging to teach during
      residency training. We undertook this study to evaluate the impact of a case
      based, reflective practice (RP) curriculum on the attitudes of radiology
      residents about professionalism. MATERIALS AND METHODS: We developed a case-based
      radiology-specific RP curriculum focused on topics related to professionalism and
      ethics. This year-long curriculum was comprised of six individual sessions and
      was attended by radiology residents. We assessed the program using the Penn State
      College of Medicine Professionalism Questionnaire, a validated instrument
      designed to assess attitudes toward professionalism, with anonymous responses
      collected before and after completion of the 1-year curriculum. We also obtained
      feedback on individual sessions. RESULTS: Our curriculum affected the
      professional attitudes of residents in 7 of 36 sample items on the
      professionalism questionnaire (P <0.05), when analyzed as unpaired data. When
      stratified into seven specific elements of professionalism, significant
      differences in resident response were identified in the areas of accountability,
      honor and integrity, enrichment, and duty. Furthermore, residents generally
      agreed that the individual sessions were meaningful and were important to their
      future careers (3.8-4.4 on a five-point scale). CONCLUSIONS: A case-based, RP
      curriculum centered about professionalism offers a unique practical approach to
      expose residents to the concepts of professionalism and ethics in a small group
      setting. Based on a widely used validated survey instrument, our results indicate
      that this method raises resident awareness about professionalism and impacts the
      way in which residents think about this topic and their eventual career.

PMID- 25863797
TI  - Ambulatory respiratory rate trends identify patients at higher risk of worsening
      heart failure in implantable cardioverter defibrillator and biventricular device
      recipients: a novel ambulatory parameter to optimize heart failure management.
AB  - PURPOSE: Respiratory distress is the primary driver for heart failure (HF)
      hospitalization. Implantable pacemakers and defibrillators are capable of
      monitoring respiratory rate (RR) in ambulatory HF patients. We investigated
      changes in RR prior to HF hospitalizations and its near-term risk stratification
      power. METHODS: NOTICE-HF was an international multi-center study. Patients were
      implanted with an implantable cardioverter defibrillator or cardiac
      resynchronization therapy defibrillator, capable of trending daily maximum,
      median, and minimum RR (maxRR, medRR, minRR). RR from 120 patients with 9 months
      of follow-up was analyzed. One-tailed Student's t test was used to compare RR
      values prior to HF events to baseline defined as 4 weeks prior to the events. A
      Cox regression model was used to calculate the hazard ratios (HR) for the 30-day
      HF hospitalization risk based on RR values in the preceding month. RESULTS: Daily
      maxRR, medRR, and minRR were significantly elevated prior to HF events compared
      to baseline (DeltamaxRR 1.8 +/- 3.0; p = 0.02; DeltamedRR, 2.1 +/- 2.8; p =
      0.007; DeltaminRR, 1.5 +/- 2.1, p = 0.008). Risk of experiencing HF events within
      30-days was increased if the standard deviation of medRR over the preceding month
      was above 1.0 br/min (HR = 12.3, 95 % confidence interval (CI) 2.57-59, p =
      0.002). The risk remained high after adjusting for clinical variables that
      differed at enrollment. CONCLUSION: Ambulatory daily respiratory rate trends may
      be a valuable addition to standard management for HF patients.

PMID- 25863798
TI  - The Thebesian valve and coronary sinus in cardiac magnetic resonance.
AB  - PURPOSE: There is no complex research exploring usefulness of cardiac magnetic
      resonance in the evaluation of the coronary sinus including Thebesian valve,
      which can be useful before selected electrophysiology procedures. METHODS: One
      hundred twenty-two patients aged 49.2 +/- 17.2 (42 women) were included in the
      study; 4 of them were excluded. A steady-state free-precession (SSFP) sequence
      was the basis of the visualization and analysis of the coronary sinus as well as
      Thebesian valve. In selected cases, dedicated coronary sinus sequences were
      created. All data were evaluated by experienced cardiac magnetic resonance
      investigators. RESULTS: We were able to visualize the coronary sinus by using
      basic SSFP sequence in all patients, however in four cases in suboptimal quality.
      Average length of the coronary sinus was 39.73 +/- 16.9 mm, average diameter was
      9.81 +/- 9.3 mm, and average angle of the entrance of the coronary sinus into the
      right atrium was 111.37 +/- 13.8 degrees . The Thebesian valve as the gate of the
      coronary sinus was found in 56 cases (45.9%). In 21 patients (17.2% of all), the
      valve was porous or almost totally covered the coronary sinus ostium, which can
      potentially create problems during CS cannulation. CONCLUSIONS: In most of the
      cases, it is possible to visualize and measure the coronary sinus using cardiac
      magnetic resonance with SSFP sequence. In selected cases, it is necessary to
      perform additional dedicated short sequences. Thebesian valve was visualized in
      almost 50% of patients.

PMID- 25863799
TI  - Role of yoga as an adjunctive therapy in patients with neurocardiogenic syncope:
      a pilot study.
AB  - BACKGROUND: Neurocardiogenic syncope (NCS) is a common clinical condition
      characterized by abrupt cardiovascular autonomic changes resulting in syncope.
      This is a recurring condition with mixed results from current strategies of
      treatment. METHODS: Subjects with a diagnosis of NCS were screened and enrolled.
      All the participants were given a DVD containing yoga videos and were instructed
      to practice yoga therapy for 60 min, three times a week for 3 consecutive months.
      Syncope functional status questionnaire score (SFSQS) was administered at the
      beginning and the end of the study. The subjects were followed for 3 months and
      underwent repeat tilt table testing at the end of the study. RESULTS: Of the 60
      patients screened, 44 subjects were enrolled, 21 in the intervention group and 23
      in the control group. Most of the participants were females, and the mean age was
      21 +/- 3 years. In the intervention group, who finished the yoga regimen, there
      was a statistically significant improvement from control phase to the
      intervention phase, in number of episodes of syncope (4 +/- 1 vs 1.3 +/- 0.7, p <
      0.001) and presyncope (4.7 +/- 1.5 vs 1.5 +/- 0.5, p < 0.001). The mean SFSQS
      also decreased from 67 +/- 7.8 to 29.8 +/- 4.6 (p < 0.001). All subjects had
      positive head up tilt table (HUTT) study at the time of enrollment compared to
      only six patients at the completion of intervention phase (10/100 vs 6/28 %, p <
      0.0001). CONCLUSION: Yoga therapy can potentially improve the symptoms of
      presyncope and syncope in young female patients with NCS.

PMID- 25863800
TI  - The genetic basis for inherited forms of sinoatrial dysfunction and
      atrioventricular node dysfunction.
AB  - The sinoatrial node (SAN) and the atrioventricular node (AVN) are the anatomical
      and functional regions of the heart which play critical roles in the generation
      and conduction of the electrical impulse. Their functions are ensured by peculiar
      structural cytological properties and specific collections of ion channels.
      Impairment of SAN and AVN activity is generally acquired,but in some cases
      familial inheritance has been established and therefore a genetic cause is
      involved. In recent years, combined efforts of clinical practice and experimental
      basic science studies have identified and characterized several causative gene
      mutations associated with the nodal syndromes. Channelopathies, i.e., diseases
      associated with defective ion channels, remain the major cause of genetically
      determined nodal arrhythmias; however, it is becoming increasingly evident that
      mutations in other classes of regulatory and structural proteins also have
      profound pathophysiological roles. In this review, we will present some aspects
      of the genetic identification of the molecular mechanism underlying both SAN and
      AVN dysfunctions with a particular focus on mutations of the Na, pacemaker (HCN),
      and Ca channels. Genetic defects in regulatory proteins and calcium-handling
      proteins will be also considered. In conclusion, the identification of the
      genetic defects associated with familial nodal dysfunction is an essential step
      for implementing an appropriate therapeutic treatment. 

PMID- 25863801
TI  - Selection of DNA aptamers for ovarian cancer biomarker HE4 using CE-SELEX and
      high-throughput sequencing.
AB  - The development of novel affinity probes for cancer biomarkers may enable
      powerful improvements in analytical methods for detecting and treating cancer. In
      this report, we describe our use of capillary electrophoresis (CE) as the
      separation mechanism in the process of selecting DNA aptamers with affinity for
      the ovarian cancer biomarker HE4. Rather than the conventional use of cloning and
      sequencing as the last step in the aptamer selection process, we used high
      throughput sequencing on an Illumina platform. This data-rich approach, combined
      with a bioinformatics pipeline based on freely available computational tools,
      enabled the entirety of the selection process-and not only its endpoint-to be
      characterized. Affinity probe CE and fluorescence anisotropy assays demonstrate
      the binding affinity of a set of aptamer candidates identified through this
      bioinformatics approach. Graphical Abstract A population of candidate aptamers is
      sequenced on an Illumina platform, enabling the process by which aptamers are
      selected over multiple SELEX rounds to be characterized. Bioinformatics tools are
      used to identify enrichment of selected aptamers and groupings into clusters
      based on sequence and structural similarity. A subset of sequenced aptamers may
      be intelligently chosen for in vitro testing. 

PMID- 25863802
TI  - Determination of Synacthen((r)) in dried blood spots for doping control analysis
      using liquid chromatography tandem mass spectrometry.
AB  - Dried blood spot (DBS) sampling, a technique used for taking whole blood samples
      dried on a filter paper, was initially reported in 1963 by Robert Guthrie. While
      the diagnostic analysis of metabolic disorders in newborns was the focus of
      investigations at that time, the number of established applications for
      preclinical drug development, toxicological studies, and therapeutic drug
      monitoring increased enormously in the last decades. As a consequence of speed,
      simplicity, and minimal invasiveness, DBS recommends itself as the preferential
      technique in sports drug testing. The present approach highlights for the first
      time the development of a screening assay for the analysis of the synthetic human
      adrenocorticotropic hormone tetracosactide hexaacetate (Synacthen((r))) in DBS
      using liquid chromatography tandem mass spectrometry. Highly purified sample
      extracts were obtained by an advanced sample preparation procedure including the
      addition of an internal standard (d8-tetracosactide) and immunoaffinity
      purification. The method's overall recovery was 27.6 %, and the assay's
      imprecision was calculated between 8.1 and 17.9 % for intraday and 12.9 to 20.5 %
      for interday measurements. Stability of the synthetic peptide in DBS was shown
      for at least 10 days at room temperature and presents a major benefit, since a
      rapid degradation in conventionally applied matrices such as urine or plasma is
      well known. With a limit of detection of 50 pg/mL, a detection window of several
      hours is expected considering reported steady-state plasma levels of 300 pg/mL
      after intramuscular application of Synacthen((r)) Depot (1 mg). The analysis of
      authentic DBS samples within the scope of an administration study with 250 MUg
      Synacthen((r)) (short stimulation test) demonstrated the great potential of the
      developed assay to simplify the analysis of Synacthen((r)) for doping control
      purposes.

PMID- 25863803
TI  - [Mechanical methods for cervical ripening in France: An evaluation of
      professional practices].
AB  - OBJECTIVE: Mechanical methods for cervical ripening are as effective as
      prostaglandins for the rate of vaginal delivery. Our aim was to study
      professional practices of mechanical cervical ripening in France. METHODS: A
      declarative survey was conducted among two groups of maternity units: a sample
      representative of French maternity units (group 1) and on the whole of type 3
      maternity units (group 2). A questionnaire was emailed to physicians of these
      obstetric units between May and July 2014. RESULTS: Forty-three of the 104 units
      (41.3%) in the first group and 43 of the 64 units in the second group (67.2%)
      answered the questionnaire. Among these maternity units, mechanical methods were
      used respectively in 44.2 and 69.8% of the establishments. The two main devices
      used were the trans-cervical balloon catheter and the Foley catheter. The main
      indication for mechanical methods was induction of labor with prior caesarean. In
      case of induction of labor, a prior caesarean and a Bishop score < 7, in the
      first group, 46.6% of the maternity units did a caesarean, 32.3% performed an
      induction of labor with mechanical methods, 13.9% with oxytocin and 6.9% with
      prostaglandins. In the second group, 25.6% of maternity units performed a
      caesarean, 53.6% used mechanical methods, 9.3% used oxytocin and 11.6% used
      prostaglandins. CONCLUSION: In France nearly half of the maternity units and
      nearly three-quarters of type 3 maternity units say they use mechanical cervical
      ripening, mainly used in case of prior caesarean.

PMID- 25863804
TI  - Impact of drug-eluting balloon (pre- or post-) dilation on neointima formation in
      de novo lesions treated by bare-metal stent: the IN-PACT CORO trial.
AB  - The efficacy of DEB in modifying the high restenosis risk associated with BMS
      implantation is doubtful. Optical coherence tomography (OCT) may allow precise
      assessment of neointimal formation after stent implantation. We performed a
      single-center, prospective, 1:2 randomized trial comparing BMS implantation alone
      (BMS group) vs. additional DEB (DEB group). DEB patients were further randomized
      1:1 to DEB before stenting (pre-DEB group), or after stenting (post-DEB group).
      Primary endpoint was OCT-assessed neointimal hyperplasia (expressed both as mean
      in-stent neointimal area and as percentage obstruction of the mean stent area) at
      6 months. Secondary endpoints were the percentage of uncovered and malapposed
      stent struts. Thirty patients were enrolled and randomized to BMS (n = 10), pre
      DEB (n = 10), post-DEB (n = 10). At 6-month OCT follow-up, DEB significantly
      reduced neointimal area compared with BMS: mean neointimal area 2.01 +/- 0.89 vs.
      3.03 +/- 1.07 mm(2) (p = 0.02), percentage area obstruction 24.56 +/- 12.50 vs.
      37.51 +/- 12.26 % (p = 0.02). The percentage of uncovered and malapposed stent
      struts did not differ significantly between BMS and DEB. In the comparison
      between pre-DEB and post-DEB, no significant difference was observed for both
      primary and secondary endpoints. In de novo coronary lesions treated with BMS,
      DEB use could be associated with a mild reduction in neointimal hyperplasia at 6
      months; this effect could be unrelated to the timing of DEB dilation (pre- or
      post-stenting). CLINICAL TRIAL REGISTRATION INFORMATION:
      http://www.clinicaltrials.gov . Identifier: NCT01057563.

PMID- 25863805
TI  - Impact of oral beta-blocker therapy on mortality after primary percutaneous
      coronary intervention for Killip class 1 myocardial infarction.
AB  - The use of beta-blockers therapy has been recommended to reduce mortality in
      patients with left ventricular dysfunction after acute myocardial infarction
      (AMI). Primary percutaneous coronary intervention (PCI), which has become the
      mainstay of treatment for AMI, is associated with a lower mortality than
      fibrinolysis. The benefits of beta-blockers after primary PCI in AMI patients
      without pump failure are unclear. We hypothesized that oral beta-blocker therapy
      after primary PCI might reduce the mortality in AMI patients without pump
      failure. The assessment of lipophilic vs. hydrophilic statin therapy in acute
      myocardial infarction (ALPS-AMI) study was a multi-center study that enrolled 508
      AMI patients to compare the efficacy of hydrophilic and lipophilic statins in
      secondary prevention after myocardial infarction. We prospectively tracked
      cardiovascular events for 3 years in 444 ALPS-AMI patients (median age 66 years;
      18.2 % women) who had Killip class 1 on admission and were discharged alive. The
      primary endpoint was all-cause mortality. The 3-year follow-up was completed in
      413 patients (93.0 %). During this follow-up, 21 patients (4.7 %) died. In Kaplan
      Meier analysis, patients on beta-blockers had a significantly lower incidence of
      all-cause mortality (2.7 vs. 7.3 %, log-rank p = 0.025). After adjusting for the
      calculated propensity score for using beta-blockers, their use remained an
      independent predictor of all-cause mortality (hazard ratio 0.309; 95 % confidence
      interval 0.116-0.824; p = 0.019). In the statin era, the use of beta-blocker
      therapy after primary PCI is associated with lower mortality in AMI patients with
      Killip class 1 on admission. 

PMID- 25863806
TI  - Increased cystatin C levels as a risk factor of cardiovascular events in patients
      with preserved estimated glomerular filtration rate after elective percutaneous
      coronary intervention with drug-eluting stents.
AB  - Chronic kidney disease (CKD) is an important risk factor for coronary artery
      disease (CAD) and cardiovascular events. Cystatin C (CysC) has been proposed as a
      sensitive marker for CKD. However, the predictive value of CysC for
      cardiovascular events in CAD patients with preserved estimated glomerular
      filtration rate (eGFR) is unclear. We enrolled 277 consecutive patients
      undergoing elective percutaneous coronary intervention with sirolimus-eluting
      stents (SES). Patients with an eGFR <=60 ml/min/1.73 m(2) were excluded. Serum
      CysC levels were measured immediately before SES implantation. Major adverse
      cardiac and cerebrovascular events (MACCE) were defined as cardiovascular death,
      acute coronary syndrome, stroke, and hospitalization because of congestive heart
      failure. After a median follow-up of 63 months, 29 patients had MACCE. The
      subjects were divided into 2 groups based on median serum CysC levels and eGFR
      (0.637 mg/L and 72.43 ml/min/1.73 m(2), respectively). Kaplan-Meier curves showed
      that the high CysC group had a significantly higher occurrence of MACCE than the
      low CysC group (p = 0.006), although a low level of eGFR was not significantly
      associated with an increased risk for occurrence of MACCE. Multivariate analysis
      revealed that serum CysC levels were an independent predictor of MACCE [hazards
      ratio: 1.30 per 0.1 mg/L (1.01-1.63), p = 0.038]. These data suggested that serum
      CysC level is an independent predictor of MACCE, even in patients with preserved
      eGFR after elective SES implantation. 

PMID- 25863807
TI  - Current advances in the synthesis and biological potencies of tri- and tetra
      substituted 1H-imidazoles.
AB  - In this report, we review the current chemistry progress and in particular the
      synthesis approaches of tri- and tetra-substituted imidazoles. 

PMID- 25863808
TI  - Congenital heart disease in the adult: what should the adult cardiologist know?
AB  - There is an increasing population of adults with congenital heart disease (CHD)
      due to successful pediatric medical and surgical intervention, and commensurate
      with this increase is a rise in heart failure, hospital admissions, and hospital
      costs among adult CHD patients. This group of patients requires careful long-term
      evaluation and follow-up of the residua and sequelae of their cardiac anomalies
      that arise in adulthood to prevent late complications. This article addresses
      congenital heart defects that are encountered in a general adult cardiology
      practice and reviews clinical, anatomic, and imaging features of each lesion,
      fundamental management issues, indications for interventions (and often re
      interventions), issues related to endocarditis prophylaxis, pregnancy, and
      appropriateness of referral to a dedicated adult CHD program for long-term care. 

PMID- 25863809
TI  - Antithrombotic therapy in patients undergoing TAVI with concurrent atrial
      fibrillation. One center experience.
AB  - Aim of the present study was to record the antithrombotic approach in AF and non
      AF patients undergoing TAVI, and to compare the efficiency of the used regimens
      combination. Antithrombotic approach of patients undergoing TAVI remains a
      challenging dispute. It becomes even more complex when need for anticoagulant
      treatment is required due to concurrent atrial fibrillation. Consecutive patients
      with severe symptomatic aortic stenosis treated with TAVI, were retrospectively
      studied. All patients were divided into two groups, matched to age, depending on
      the existence of atrial fibrillation. The primary end-point was the composite of
      MACE, while the secondary end-point was the occurrence of major bleeding at
      follow-up. A total of 80 patients were included in the study. Out of them, 20
      patients (80.2 +/- 5.4 years) suffered from concurrent atrial fibrillation. This
      group was matched with 20 patients (80.6 +/- 3.7 years) with no need for
      anticoagulation. AF-group patients were treated with clopidogrel plus
      acenocoumarol for 3 months. Following that, acetylsalicylic acid plus
      acenocoumarol were prescribed. Non-AF patients were treated with 3 months
      clopidogrel plus acetylsalicylic acid followed by single acetylsalicylic acid
      medication. No statistical significant differences in MACE between AF and non-AF
      group were identified (p = 0.705, phi coefficient = 0.06) (mean follow-up 23.4 +/
      14 months). Similarly, there was no statistical significant difference for
      bleedings among the AF and non-AF patient group (p = 0.658, phi coefficient =
      0.14). In patients undergoing TAVI with CoreValve, with concurrent AF, treatment
      with clopidogrel plus acenocoumarol for 3 months, followed by acetylsalicylic
      acid plus acenocoumarol, seems safe and effective enough in long-term follow-up.

PMID- 25863810
TI  - A Report of Two Cases of Leptomeningeal Carcinomatosis Arising from Gallbladder
      Carcinoma.

PMID- 25863811
TI  - Validating the cross-cultural factor structure and invariance property of the
      Insomnia Severity Index: evidence based on ordinal EFA and CFA.
AB  - OBJECTIVE: The purpose of this study is to examine the factor structure of the
      Insomnia Severity Index (ISI) across samples recruited from different countries.
      We tried to identify the most appropriate factor model for the ISI and further
      examined the measurement invariance property of the ISI across samples from
      different countries. METHODS: Our analyses included one data set collected from a
      Taiwanese sample and two data sets obtained from samples in Hong Kong and Canada.
      The data set collected in Taiwan was analyzed with ordinal exploratory factor
      analysis (EFA) to obtain the appropriate factor model for the ISI. After that, we
      conducted a series of confirmatory factor analyses (CFAs), which is a special
      case of the structural equation model (SEM) that concerns the parameters in the
      measurement model, to the statistics collected in Canada and Hong Kong. The
      purposes of these CFA were to cross-validate the result obtained from EFA and
      further examine the cross-cultural measurement invariance of the ISI. RESULTS:
      The three-factor model outperforms other models in terms of global fit indices in
      Taiwan's population. Its external validity is also supported by confirmatory
      factor analyses. Furthermore, the measurement invariance analyses show that the
      strong invariance property between the samples from different cultures holds,
      providing evidence that the ISI results obtained in different cultures are
      comparable. CONCLUSIONS: The factorial validity of the ISI is stable in different
      populations. More importantly, its invariance property across cultures suggests
      that the ISI is a valid measure of the insomnia severity construct across
      countries.

PMID- 25863813
TI  - Cerebellar Contribution to Context Processing in Extinction Learning and Recall.
AB  - Whereas acquisition of new associations is considered largely independent of the
      context, context dependency is a hallmark of extinction of the learned
      associations. The hippocampus and the prefrontal cortex are known to be involved
      in context processing during extinction learning and recall. Although the
      cerebellum has known functional and anatomic connections to the hippocampus and
      the prefrontal cortex, cerebellar contributions to context processing of
      extinction have rarely been studied. In the present study, we reanalyzed
      functional brain imaging data (fMRI) of previous work investigating context
      effects during extinction in a cognitive associative learning paradigm in 28
      young and healthy subjects (Lissek et al. Neuroimage. 81:131-3, 2013). In that
      study, event-related fMRI analysis did not include the cerebellum. The 3 T fMRI
      dataset was reanalyzed using a spatial normalization method optimized for the
      cerebellum. Data of seven participants had to be excluded because the cerebellum
      had not been scanned in full. Cerebellar activation related to context change
      during extinction learning was most prominent in lobule Crus II bilaterally (p <
      0.01, t > 2.53; partially corrected by predetermined cluster size). No
      significant cerebellar activations were observed related to context change during
      extinction retrieval. The posterolateral cerebellum appears to contribute to
      context-related processes during extinction learning, but not (or less) during
      extinction retrieval. The cerebellum may support context learning during
      extinction via its connections to the hippocampus. Alternatively, the cerebellum
      may support the shifting of attention to the context via its known connections to
      the dorsolateral prefrontal cortex. Because the ventromedial prefrontal cortex
      (vmPFC) is critically involved in context-related processes during extinction
      retrieval, and there are no known connections between the cerebellum and the
      vmPFC, the cerebellum may be less important during extinction recall. 

PMID- 25863814
TI  - Short communication: Transmission of border disease virus to seronegative cows
      inseminated with infected semen.
AB  - The goal of this study was to investigate the transmissibility of border disease
      (BD) virus to seronegative cows via artificial insemination with cryopreserved
      semen from a bull persistently infected with BD virus. Five pestivirus naive cows
      were inseminated with BD virus-infected semen. Blood was collected for detection
      of pestivirus antibody by means of an ELISA on day 0 (day of insemination) and
      then every 7 days until day 56, at which time a serum neutralisation test (SNT)
      for differentiation of BD and BVD virus was carried out. Seroconversion was first
      noticed in two cows on day 14, in two cows on day 21 and in one cow on day 28. In
      the SNT, all cows had distinctly positive titres against BD virus. Therefore, BD
      virus is readily transmitted by infected semen, but none of the cows conceived,
      most likely because of poor semen quality. 

PMID- 25863815
TI  - Halonium Ions as Halogen Bond Donors in the Solid State [XL2]Y Complexes.
AB  - The utilization of halogen bonding interactions is one of the most rapidly
      developing areas of supramolecular chemistry. While the other weak non-covalent
      interactions and their influence on the structure and chemistry of various
      molecules, complexes, and materials have been investigated extensively, the
      understanding, utilizations, and true nature of halogen bonding are still
      relatively unexplored. Thus its final impact in chemistry in general and in
      materials science has not yet been fully established. Because of the polarized
      nature of a Z-X bond (Z=electron-withdrawing atom or moiety and X=halogen atom),
      such a moiety can act as halogen bond donor when the halogen is polarized enough
      by the atom/moiety Z. The most studied and utilized halogen bond donor molecules
      are the perfluorohalocarbons, where Z is a perfluorinated aryl or alkyl moiety
      and X is either iodine or bromine. Complementing the contemporary halogen bonding
      research, this chapter reviews the solid state structural chemistry of the most
      extremely polarized halogen atoms, viz. halonium ions, X+, and discussed them as
      halogen bond donors in the solid state [XL2]Y complexes (X=halonium ion, Y=any
      anion).

PMID- 25863812
TI  - Maternal immune activation produces cerebellar hyperplasia and alterations in
      motor and social behaviors in male and female mice.
AB  - There have been suggestions that maternal immune activation is associated with
      alterations in motor behavior in offspring. To explore this further, we treated
      pregnant mice with polyinosinic:polycytidylic acid (poly(I:C)), a viral mimetic
      that activates the innate immune system, or saline on embryonic days 13-15. At
      postnatal day (P) 18, offspring cerebella were collected from perfused brains and
      immunostained as whole-mounts for zebrin II. Measurements of zebrin II+/- stripes
      in both sexes indicated that prenatal poly(I:C)-exposed offspring had
      significantly wider stripes; this difference was also seen in similarly treated
      offspring in adulthood (~P120). When sagittal sections of the cerebellum were
      immunostained for calbindin and Purkinje cell numbers were counted, we observed
      greater numbers of Purkinje cells in poly(I:C) offspring at both P18 and ~ P120.
      In adolescence (~P40), both male and female prenatal poly(I:C)-exposed offspring
      exhibited poorer performance on the rotarod and ladder rung tests; deficits in
      performance on the latter test persisted into adulthood. Offspring of both sexes
      from poly(I:C) dams also exhibited impaired social interaction in adolescence,
      but this difference was no longer apparent in adulthood. Our results suggest that
      maternal immune exposure at a critical time of cerebellum development can enhance
      neuronal survival or impair normal programmed cell death of Purkinje cells, with
      lasting consequences on cerebellar morphology and a variety of motor and non
      motor behaviors. 

PMID- 25863816
TI  - Nonlinear Spectroscopy of Core and Valence Excitations Using Short X-Ray Pulses:
      Simulation Challenges.
AB  - Measuring the nonlinear response of electrons and nuclei to attosecond broadband
      X-ray radiation has become possible by newly developed free electron lasers and
      high harmonic generation light sources. The design and interpretation of these
      novel experiments poses considerable computational challenges. In this chapter we
      survey the basic description of nonlinear X-ray spectroscopy signals and the
      electronic structure protocols which may be used for their simulation. 

PMID- 25863818
TI  - Development, implementation and evaluation of an interprofessional graduate
      program for nursing-paramedicine double-degree graduates.
AB  - Over the past decade, several Australian universities have offered a double
      degree in nursing and paramedicine. Mainstream employment models that facilitate
      integrated graduate practice in both nursing and paramedicine are currently
      lacking. The aim of the present study was to detail the development of the
      Interprofessional Graduate Program (IPG), the industrial and professional issues
      that required solutions, outcomes from the first pilot IPG group and future
      directions. The IPG was an 18-month program during which participants rotated
      between graduate nursing experience in emergency nursing at Northern Health,
      Melbourne, Australia and graduate paramedic experience with Ambulance Victoria.
      The first IPG with 10 participants ran from January 2011 to August 2012. A survey
      completed by nine of the 10 participants in March 2014 showed that all nine
      participants nominated Ambulance Victoria as their main employer and five
      participants were working casual shifts in nursing. Alternative graduate programs
      that span two health disciplines are feasible but hampered by rigid industrial
      relations structures and professional ideologies. Despite a 'purpose built'
      graduate program that spanned two disciplines, traditional organisational
      structures still hamper double-degree graduates using all of skills to full
      capacity, and force the selection of one dominant profession.

PMID- 25863819
TI  - Risk and resilience factors associated with posttraumatic stress in ethno
      racially diverse National Guard members in Hawai'i.
AB  - This study examinedrisk and resilience factors associated with posttraumatic
      stress symptomatology (PTSS) in an ethno-racially diverse sample of Hawai'i
      National Guard members comprised of Native Hawaiians, Filipino Americans,
      Japanese Americans, and European Americans. In the full sample, identifying as
      Japanese American and higher scores on measures of perceived social support and
      psychological resilience were negatively associated with PTSS, while Army Guard
      (vs. Air Guard) status and stronger family norms against disclosing mental health
      problems were positively associated with PTSS. Exploratory analyses of ethno
      racial subgroups identified different patterns of within and between-group
      correlates of PTSS. For example, when controlling for other factors, higher
      psychological resilience scores were negatively associated with PTSS only among
      Native Hawaiian and European Americans. Overall, results of this study suggest
      that some risk and resilience factors associated with posttraumatic stress
      disorder (PTSD) may extend to military populations with high numbers of Filipino
      American, Japanese American, and Native Hawaiian Veterans. Results further
      suggest differences in risk and resilience factors unique to specific ethno
      racial subgroups. 

PMID- 25863817
TI  - Chemical and biological tools for the preparation of modified histone proteins.
AB  - Eukaryotic chromatin is a complex and dynamic system in which the DNA double
      helix is organized and protected by interactions with histone proteins. This
      system is regulated through a large network of dynamic post-translational
      modifications (PTMs) which ensure proper gene transcription, DNA repair, and
      other processes involving DNA. Homogenous protein samples with precisely
      characterized modification sites are necessary to understand better the functions
      of modified histone proteins. Here, we discuss sets of chemical and biological
      tools developed for the preparation of modified histones, with a focus on the
      appropriate choice of tool for a given target. We start with genetic approaches
      for the creation of modified histones, including the incorporation of genetic
      mimics of histone modifications, chemical installation of modification analogs,
      and the use of the expanded genetic code to incorporate modified amino acids. We
      also cover the chemical ligation techniques which have been invaluable in the
      generation of complex modified histones indistinguishable from their natural
      counterparts. We end with a prospectus on future directions. 

PMID- 25863820
TI  - Inside the mind of poor Tom--A multidimensional approach to determine causes for
      redundant clothing in patients with schizophrenia.
AB  - Redundant clothing (RC) is a readily observable feature of schizophrenia. While
      abnormal thermoregulation, thyroid dysfunction and autonomic dysregulation have
      been postulated to account for RC, no identified factor yet conclusively explains
      this enigmatic behaviour. This study attempted to determine the cause(s) of RC in
      schizophrenia. Two groups of 20 age- and sex-matched patients with and without RC
      were studied. Socio-demographic and clinical characteristics were recorded, and
      patients were assessed for psychopathology (Positive and Negative Syndrome Scale
      (PANSS)), cognitive function (Schizophrenia Cognition Rating Scale (SCoRS)), and
      autonomic and thyroid function. Those with RC differed significantly from those
      without RC in education, occupation, marital status and duration of untreated
      psychosis (DUP). They were more disorganised, more withdrawn, and had significant
      affective impairment. The RC group also had significantly higher negative,
      general and total psychopathology scores on the Positive and Negative Syndrome
      Scale, significantly poorer cognitive function, greater autonomic dysfunction,
      and lower free T3 and free T4 concentrations. We propose that the dimension of RC
      could define a subgroup with poorer premorbid functioning and a longer DUP, in
      whom cognitive dysfunction and prominent negative symptoms coloured the
      manifestations of deranged thermoregulation secondary to lower thyroid hormone
      levels and autonomic dysfunction, ultimately resulting in redundant clothing. 

PMID- 25863821
TI  - The inoculating role of previous exposure to potentially traumatic life events on
      coping with prolonged exposure to rocket attacks: A lifespan perspective.
AB  - Relatively little research have addressed the effect of prolonged exposure to
      rocket attacks with a lifespan perspective and only a handful of these studies
      focused on the effect of this exposure as a function of aging. The present study
      examined the effects of seven years of rocket attacks fired toward the south of
      Israel on adult participants of different ages. We examined whether potentially
      traumatic life events (PTLEs) unrelated to rocket attacks moderated the
      association between post-traumatic stress (PTS) symptoms and age. Data were
      obtained from a 2007 telephone survey using the Random Digit Dialing method and
      including 343 individuals (76.7% participation rate). Exposure to rockets, PTLEs,
      global distress, and post-traumatic symptomatology were assessed. Older age was
      associated with a higher level of PTS symptoms. Higher PTLE levels attenuated the
      association between age and PTS symptoms. Our results suggest that age is a risk
      factor for developing PTS symptoms under prolonged exposure to rocket attacks.
      However, previous levels of exposure to other negative events, as well as gender,
      appear to inoculate a person to stress, thus modulating the age-PTS association. 

PMID- 25863822
TI  - Prevalence and correlates of co-prescribing psychotropic medications with long
      term opioid use nationally in the Veterans Health Administration.
AB  - We used national data for fiscal year 2012 to examine demographic, psychiatric
      and medical diagnoses, indications for psychotropics, and service use correlates
      of psychotropic medication fills in Veterans with at least 10 opioid
      prescriptions during the year (the highest 29% of opioid users); and whether the
      Veteran was treated in a specialty mental health clinic. Of the 328,398 Veterans
      who filled at least 10 opioid prescriptions, 77% also received psychotropics, of
      whom: 74% received antidepressants, 55% anxiolytics/sedatives/hypnotics, and 26%
      three or more classes of psychotropic medications. Altogether, 87% had a
      psychiatric or medical indication; and 54% received mental health treatment.
      Veterans treated in a mental health clinic were prescribed more psychotropics and
      were more likely to have a documented psychiatric or medical indication than
      those treated solely in other settings. Indicated psychiatric diagnoses were the
      strongest predictors of specific class of psychotropics prescribed; anxiety
      disorder and insomnia were most strongly associated with
      anxioloytics/sedatives/hypnotics receipt. Since psychotropics and opioids can
      produce harmful side effects, especially when combined, and since they are likely
      prescribed by separate providers in different settings, coordinated consideration
      of the risks and benefits of co-prescribing these medications may be needed,
      along with further study of related adverse events. 

PMID- 25863823
TI  - The association of military and premilitary sexual trauma with risk for suicide
      ideation, plans, and attempts.
AB  - Military sexual trauma is a strong predictor of psychiatric disorders and
      negative health outcomes among military personnel and veterans, but little is
      known about its relationship with suicide risk. The current study investigates
      the association of military sexual trauma with suicide risk among 464 U.S.
      military personnel and veterans enrolled in college classes. Results indicate
      that premilitary sexual assault was associated with significantly increased risk
      for later suicide ideation, plans, and attempts during military service. Unwanted
      sexual experiences occurring during military service was associated with
      significantly increased risk for suicide ideation and suicide plans for male
      participants. When considered simultaneously, premilitary sexual trauma showed
      relatively stronger associations with suicide risk among women whereas military
      sexual trauma showed relatively stronger associations with suicide risk among
      men. Results suggest differences in the relation of sexual trauma to suicide risk
      among male and female military personnel and veterans. 

PMID- 25863824
TI  - Dopamine supersensitivity psychosis as a pivotal factor in treatment-resistant
      schizophrenia.
AB  - There may be subtypes in treatment-resistant schizophrenia (TRS), and one of the
      subtypes may be related to dopamine supersensitivity psychosis (DSP). In
      developing strategies for prevention and treatment TRS, it is important to
      clarify the role of DSP in TRS. TRS patients were recruited from 3 hospitals for
      the present study. Through chart reviews, all patients were judged as either TRS
      or not, and then possible TRS patients were investigated about their past/present
      histories of DSP episode(s) by direct interviews. We then compared each factor
      between the groups with and without DSP episode(s). Out of 611 patients screened,
      147 patients met the criteria for TRS and were included in the present analysis.
      These were divided into groups with and without DSP, comprising 106 (72.1%) and
      41 patients (27.9%), respectively. Clinical characteristics in the two groups
      were similar, except for drug-induced movement disorders (DIMDs), which were
      significantly more important in DSP patients. Of the DSP patients, 42% and 56%
      experienced rebound psychosis and tolerance to antipsychotic effects,
      respectively. The present study revealed that approximately 70% of TRS patients
      experienced one or more DSP episodes, which may have a strong impact on the long
      term prognosis of patients with schizophrenia. 

PMID- 25863825
TI  - The effect of maternal psychopathology on parent-child agreement of child anxiety
      symptoms: A hierarchical linear modeling approach.
AB  - The current study examined the effects of maternal anxiety, worry, depression,
      child age and gender on mother and child reports of child anxiety using
      hierarchical linear modeling. Participants were 73 mother-child dyads with
      children between the ages of 7 and 10 years. Reports of child anxiety symptoms,
      including symptoms of specific disorders (e.g., social phobia) were obtained
      using concordant versions of the Screen for Anxiety and Related Emotional
      Disorders (SCARED). Children reported significantly higher levels of anxiety
      symptoms relative to their mothers. Maternal worry and depression predicted for
      significantly lower levels of maternal-reported child anxiety and increasing
      discrepant reports. Maternal anxiety predicted for higher levels of maternal
      reported child anxiety and decreasing discrepant reports. Maternal depression was
      associated with increased child-reported child anxiety symptoms. No significant
      effect of child age or gender was observed. Findings may inform inconsistencies
      in previous studies on reporter discrepancies. Implications and future directions
      are discussed. 

PMID- 25863826
TI  - Anxiety sensitivity and sleep-related problems in anxious youth.
AB  - Anxiety disorders constitute the most common mental health disturbance
      experienced by youth. Sleep-related problems (SRPs) are highly prevalent among
      anxious youth and encompass a variety of problems including nighttime fears,
      insomnia, and refusal to sleep alone. Given that chronic sleep disturbance is
      associated with a range of behavioral and physical problems in youth and predicts
      future psychopathology, it is important to elucidate the nature of SRPs in
      anxious youth. The present study investigated the relationship between sleep
      problems and anxiety sensitivity in a sample of 101 anxious youth, ages 6-17.
      Heightened anxiety sensitivity significantly predicted prolonged sleep onset
      latency across the sample, even after accounting for severity of anxiety,
      depression, and age. Results support previous research indicating that SRPs are
      common among anxious youth and suggest that anxiety sensitivity may play a
      particularly important role in sleep onset latency. 

PMID- 25863827
TI  - Subthreshold and threshold DSM-IV generalized anxiety disorder in Singapore:
      Results from a nationally representative sample.
AB  - Previous nationally representative studies have reported prevalence of DSM-IV
      generalized anxiety disorder (GAD). However, subthreshold and threshold GAD
      expressions remain poorly understood. The current study examined the prevalence,
      correlates and co-morbidity of a broader diagnosis of GAD in Singapore. The
      Singapore Mental Health Study (SMHS) was an epidemiological survey conducted in
      the population (N=6616) aged 18 years and older. The Composite International
      Diagnostic Interview version 3.0 (CIDI 3.0) was used to establish mental disorder
      diagnoses. The lifetime prevalence for subthreshold GAD (2.1%) and threshold GAD
      (1.5%) in the current sample was found to be lower than in Western populations.
      Younger age group, Indian ethnicity, previously married, chronic physical
      conditions, and being unemployed were associated with higher odds of having more
      severe expression of generalized anxiety. The relatively lower prevalence rate of
      subthreshold GAD expression suggests possible cultural interferences in the
      reporting and manifestation of anxiety symptomatology. Despite the low
      prevalence, significant impacts on functioning and comorbidity among subthreshold
      generalized anxiety cases indicate the importance of early treatment to ensure a
      better prognosis. 

PMID- 25863829
TI  - Phosphorus content of popular beverages.

PMID- 25863828
TI  - Long-term Effects of Frequent Nocturnal Hemodialysis on Mortality: The Frequent
      Hemodialysis Network (FHN) Nocturnal Trial.
AB  - BACKGROUND: Few data are available regarding the long-term mortality rate for
      patients receiving nocturnal home hemodialysis. STUDY DESIGN: Posttrial
      observational study. SETTING & PARTICIPANTS: Frequent Hemodialysis Network (FHN)
      Nocturnal Trial participants who consented to extended follow-up. INTERVENTION:
      The FHN Nocturnal Trial randomly assigned 87 individuals to 6-times-weekly home
      nocturnal hemodialysis or 3-times-weekly hemodialysis for 1 year. Patients were
      enrolled starting in March 2006 and follow-up was completed by May 2010. After
      the 1-year trial concluded, FHN Nocturnal participants were free to modify their
      hemodialysis prescription. OUTCOMES & MEASUREMENTS: We obtained dates of death
      and kidney transplantation through July 2011 using linkage to the US Renal Data
      System and queries of study centers. We used log-rank tests and Cox regression to
      relate mortality to the initial randomization assignment. RESULTS: Median follow
      up for the trial and posttrial observational period was 3.7 years. In the
      nocturnal arm, there were 2 deaths during the 12-month trial period and an
      additional 12 deaths during the extended follow-up. In the conventional arm, the
      numbers of deaths were 1 and 4, respectively. In the nocturnal dialysis group,
      the overall mortality HR was 3.88 (95% CI, 1.27-11.79; P=0.01). Using as-treated
      analysis with a 12-month running treatment average, the HR for mortality was 3.06
      (95% CI, 1.11-8.43; P=0.03). Six-month running treatment data analysis showed an
      HR of 1.12 (95% CI, 0.44-3.22; P=0.7). LIMITATIONS: These results should be
      interpreted cautiously due to a surprisingly low (0.03 deaths/patient-year)
      mortality rate for individuals randomly assigned to conventional home
      hemodialysis, low statistical power for the mortality comparison due to the small
      sample size, and the high rate of hemodialysis prescription changes. CONCLUSIONS:
      Patients randomly assigned to nocturnal hemodialysis had a higher mortality rate
      than those randomly assigned to conventional dialysis. The implications of this
      result require further investigation.

PMID- 25863830
TI  - Impact of d-Dimer Levels on Admission on Inhospital and Long-Term Outcome in
      Patients With Type A Acute Aortic Dissection.
AB  - Limited studies with relatively small sample sizes have reported that elevated d
      dimer levels on admission were associated with increased risk of short-term
      mortality in patients with type A acute aortic dissection (AAD). However, there
      were unavailable data regarding the impact of admission d-dimer levels on long
      term outcomes. Our present study aimed to evaluate the association of admission d
      dimer levels with both inhospital and long-term all-cause mortality in patients
      with type A AAD. A total of 212 consecutive patients with type A AAD were
      enrolled. d-Dimer levels were measured on admission, and patients were followed
      up prospectively. The primary end points were inhospital and long-term all-cause
      mortality. The median length of follow-up was 18.8 months (interquartile range
      6.7 to 24.4 months). The inhospital and long-term all-cause mortality rates were
      12.7% and 12.4%, respectively. Compared with the survivors, the nonsurvivors had
      significantly higher d-dimer levels (p <0.001). When divided into 4 groups
      according to admission d-dimer quartiles, patients in Q4 (>6.10 MUg/ml) had the
      highest inhospital and long-term mortality among groups. After multivariate
      adjustment, the d-dimer level in Q4 (>6.10 MUg/ml) was an independent risk factor
      for inhospital mortality (hazard ratio [HR] 6.12, 95% confidence interval 1.35 to
      27.89, p = 0.019) in addition to surgical treatment; however, this was not an
      independent predictor for long-term mortality. In conclusion, our study with a
      relatively large sample size suggested that elevated admission d-dimer levels
      (>6.10 MUg/ml) might be a predictor for increased risk of inhospital mortality,
      and urgent-emergent surgery might be needed in patients with elevated d-dimer
      levels on admission. However, d-dimer levels at admission failed to predict long
      term mortality. 

PMID- 25863831
TI  - Priapism Impact Profile Questionnaire: Development and Initial Validation.
AB  - OBJECTIVE: To create and evaluate a psychometric instrument that measures the
      impact of experiencing priapism from the patient perspective. METHODS: The
      research protocol consisted of several phases as follows: (1) generating items,
      (2) composing a patient questionnaire, (3) administering the questionnaire to
      patients with both active and remitted (>=1 year without priapism episodes)
      histories of priapism, (4) performing internal consistency and criterion-oriented
      validity analyses in correlation with clinical histories and erectile function
      assessment tools, and (5) ascertaining psychometric properties of the instrument.
      RESULTS: The final instrument comprised a 12-item Priapism Impact Profile (PIP)
      questionnaire, representing the following 3 domains adversely impacted by
      priapism: quality of life (QoL), sexual function (SF), and physical wellness
      (PW), with higher scores indicating inferior experience in respective domains.
      Internal consistency reliability coefficients for the total PIP score and the 3
      domain scores were >0.75. Fifty-four patients (mean age, 31.7 +/- 11.4 years)
      completed the questionnaire. Patients with active priapism (n = 42) had higher
      total, QoL, SF, and PW scores than those with priapism remission (n = 8; P <.05,
      P <.05, P = .09, and P <.01, respectively). Patients with a history of recurrent
      priapism episodes >2 hours in duration had higher total, QoL, SF, and PW scores
      than those with "very minor" priapism recurrences (<=2 hours in duration; P <.01,
      P <.01, P <.05, and P <.001, respectively). Patients with "mild-to-moderate" to
      "severe" erectile dysfunction had higher total, QoL, SF, and PW scores than those
      with no or "mild" erectile dysfunction (P <.05, P = .14, P <.01, and P = .25,
      respectively). CONCLUSION: The PIP questionnaire is a novel psychometric
      instrument that offers a means to quantify the adverse health impact of the
      patient's experience with priapism.

PMID- 25863832
TI  - Are Patients Willing to Engage in Telemedicine for Their Care: A Survey of Preuse
      Perceptions and Acceptance of Remote Video Visits in a Urological Patient
      Population.
AB  - OBJECTIVE: To examine patient preuse acceptance and perceptions of video visit
      (VV) technology within an ambulatory urology setting. METHODS: Patients treated
      by a single urology department from January to June 2013 were identified. A Web
      based survey was conducted evaluating patient demographics, preuse perceptions,
      and acceptance of VV. RESULTS: In total, 1378 patients (25%) completed the
      survey; of which 868 (63%) were willing to participate in VV for their urologic
      care. Compared with patients "unlikely," those "likely" to participate in VV were
      younger (62 vs 65 years), had a college education (77% vs 65%), had previous
      exposure to videoconference technology (57% vs 38%), were more comfortable
      discussing new symptoms (56% vs 30%) and sensitive information (48% vs 27%), and
      played an active role in their healthcare (65% vs 54%). Moreover, patients
      willing to participate in VV traveled larger distances (>90 minutes; 69% vs 58%),
      missed more work (>1 day; 39% vs 29%), and incurred greater expenses for their
      care (>$250; 52% vs 25%) relative to those who were unlikely. After controlling
      for associated patient characteristics, a high level of agreement among urology
      specific questions remained independently associated with greater likelihood of
      VV acceptance among both male and female patients. CONCLUSION: A large proportion
      of patients are willing to participate in VV for their urologic care. This may
      have significant implications by reducing costs and increasing access to, and
      quality of, health care services. These findings may assist urologists in
      strategically directing future efforts to reach diverse patient populations via
      VV technology.

PMID- 25863833
TI  - Lower Urinary Tract Symptoms and Risk of Bladder Cancer in Men: Results From the
      Health Professionals Follow-up Study.
AB  - OBJECTIVE: To understand the association between lower urinary tract symptoms
      (LUTS) and risk of bladder cancer in a large cohort of men. METHODS: Using data
      from the Health Professionals Follow-up Study, we examined risk of bladder cancer
      in relation to severity of LUTS among 30,183 men. During the follow-up period
      from 1996 until 2010, 476 newly diagnosed cases of bladder cancer occurred. The
      Cox proportional hazards regression was used to adjust for potential confounders.
      RESULTS: Among men with severe LUTS, risk of bladder cancer was 64% higher
      (relative risk [RR], 1.64; 95% confidence interval [CI], 0.87-3.08) compared with
      men who reported no LUTS. Subjects with both voiding and storage dysfunction had
      a significantly higher risk of bladder cancer (RR, 1.60; 95% CI, 1.00-2.56).
      Among individual urinary symptoms, urinary hesitancy was strongly associated with
      bladder cancer; those who experienced urinary hesitancy at least 50% of the time
      had more than twice the risk of bladder cancer (RR, 2.21; 95% CI, 1.29-3.78).
      CONCLUSION: Our findings suggest that LUTS, especially urinary hesitancy, are
      associated with the development of bladder cancer in men.

PMID- 25863834
TI  - Concomitant Anterior and Posterior Urethral Valves: A Comprehensive Review of
      Literature.
AB  - Posterior urethral valves (PUVs) are the most common cause of infravesical
      obstruction in children, whereas anterior urethral valves and/or diverticula
      (AUV/D) are less commonly encountered. Concomitant AUV/D and PUV is believed to
      be very rare and may be missed on the initial evaluation. In this review, we
      provide brief information on embryology of AUV/D and PUV to explain the
      concurrent presence of these anomalies. We also summarize the information on
      published cases of concomitant AUV/D and PUV in the English literature with a
      special focus on diagnosis and the importance of both voiding cystourethrography
      and careful urethrocystoscopy. 

PMID- 25863835
TI  - For Single Dosing, Levofloxacin Is Superior to Ciprofloxacin When Combined With
      an Aminoglycoside in Preventing Severe Infections After Prostate Biopsy.
AB  - OBJECTIVE: To investigate whether there is benefit with a longer acting oral
      fluoroquinolone, we compared the rate of infection after transrectal ultrasound
      guided prostate biopsy between 2 prophylactic antibiotic regimens: ciprofloxacin
      vs levofloxacin, each combined with an aminoglycoside (AG). METHODS: A
      retrospective review was performed of all transrectal ultrasound-guided prostate
      biopsies from September 2011 to January 2013. Initially our regimen entailed 1
      dose of 500-mg ciprofloxacin and an AG. In June 2012, we switched to 1 dose of
      750-mg levofloxacin and an AG. Infections were categorized as severe if requiring
      hospital admission, overnight observation, or emergency room treatment for fever
      or chills. Those treated as an outpatient were defined as mild. RESULTS: Of 1189
      total biopsies, the total infection rate was 3.18% (17 of 535) in the
      ciprofloxacin group and 2.14% (14 of 654) in the levofloxacin group (P = .26).
      The rate of mild infection was 0.75% (4 of 535) in the ciprofloxacin group and
      1.22% (8 of 654) in the levofloxacin group (P = .56). The rate of severe
      infection was significantly higher in the ciprofloxacin group at 2.43% (13 of
      535) compared with that of 0.92% (6 of 654) in the levofloxacin group (P = .04).
      On multivariate analysis, use of ciprofloxacin rather than levofloxacin was
      associated with an increased risk of severe infection (odds ratio, 4.59; P =
      .04). CONCLUSION: Empiric prophylaxis for prostate biopsies with a single-dose
      fluoroquinolone augmented with an AG is optimal to reduce infectious
      complications. We found 750-mg levofloxacin resulted in significantly fewer
      severe infections compared with 500-mg ciprofloxacin potentially because of its
      longer half-life.

PMID- 25863836
TI  - Editorial Comment.

PMID- 25863837
TI  - Penile Squamous Cell Carcinoma After a Childhood Hypospadias Repair With Bladder
      Mucosa Graft.
AB  - Bladder mucosa grafts were historically used for hypospadias surgical repairs,
      when preputial or penile skin was unavailable and in cases of prior failed
      hypospadias repairs. We present a case of advanced penile squamous cell carcinoma
      diagnosed 22 years after a childhood hypospadias repair with a free bladder
      mucosa graft.

PMID- 25863838
TI  - Robotic-assisted Bladder Diverticulectomy: Assessment of Outcomes and
      Modifications of Technique.
AB  - OBJECTIVE: To present outcomes of robotic-assisted bladder diverticulectomy
      (RABD) and technique modifications that may improve outcomes. METHODS: Sixteen
      consecutive RABDs were performed at our institution by 2 experienced robotic
      surgeons. Charts were reviewed for patient characteristics, perioperative data,
      and long-term functional outcomes. Eleven patients (69%) underwent RABD using an
      external dissection approach, whereas 5 patients (31%) underwent RABD using a
      modified internal dissection technique (immediate entry into the bladder
      diverticulum). RESULTS: The mean age of our cohort was 68 years (range, 59-79
      years), and 15 of 16 patients (93.8%) were men. Two patients (12.5%) had known
      malignancy in the diverticulum. Eleven patients (69%) underwent a preoperative
      outlet procedure (9 transurethral resection of prostate and 2 transurethral
      incision of prostate) at a median time before RABD of 163.5 days (range, 26-622
      days). Median operative time for external RABD was 228 minutes (range, 144-353
      minutes) compared with that of 149 minutes (range, 130-189 minutes) for the
      internal dissection technique. No patient required blood transfusions, and there
      were no 30-day Clavien grade 3 or 4 complications. Median hospital stay was 2
      days (range, 1-3 days). Median postvoid residual before intervention was 458 mL
      (range, 78-1100 mL) compared with that of 214 mL (range, 46-527 mL) after RABD.
      Mean American Urological Association symptom score was 18 (range, 5-29)
      preoperatively compared with that of 7 (range, 2-21) postoperatively. CONCLUSION:
      RABD is safe with a low risk of intraoperative or postoperative complications and
      results in both improved voiding symptoms and diminished postvoid residuals.
      Modifications of technique from an external dissection approach to an internal
      dissection approach has led to a dramatic reduction in operative time.

PMID- 25863839
TI  - Editorial Comment.

PMID- 25863840
TI  - Reply: To PMID 25863832.

PMID- 25863841
TI  - Editorial Comment.

PMID- 25863842
TI  - Chronological Urodynamic Evaluation of Changing Bladder and Urethral Functions
      After Robot-assisted Radical Prostatectomy.
AB  - OBJECTIVE: To examine chronological changes in urethral and bladder functions
      before, immediately after, and 1 year after robot-assisted radical prostatectomy
      (RARP), urodynamic studies were prospectively performed. METHODS: Sixty-three
      consecutive patients underwent pressure-flow studies, urethral pressure profiles,
      and abdominal leak point pressure (ALPP) tests 1-2 days before, immediately
      after, and 1 year after RARP. RESULTS: The mean bladder compliance was 28.3 mL/cm
      H2O before RARP; it worsened to 16.3 mL/cm H2O immediately after RARP and
      recovered to 27.1 mL/cm H2O at 1 year. The mean detrusor pressure at maximum flow
      rate was 61.9 cm H2O before RARP; it decreased to 34.3 cm H2O immediately after
      RARP and remained at 35.6 cm H2O at 1 year. The mean maximum urethral closure
      pressure was 84.2 cm H2O before RARP; it decreased to 33.4 cm H2O immediately
      after RARP and recovered to 63.0 cm H2O at 1 year. Intrinsic sphincter deficiency
      (ISD) evaluated by the ALPP test was observed in 53 patients immediately after
      RARP, although no patient showed ISD before RARP. ISD remained in 7 patients at 1
      year. Both ALPP and maximum urethral closure pressure at 1 year were significant
      factors for continence in multivariate analysis. CONCLUSION: Urethral sphincter
      and bladder function worsen immediately after RARP and recover over time. The
      bladder storage function after RARP returns to almost the same level before RARP,
      and the voiding function improves compared with the condition before RARP;
      however, the urethral sphincter function does not return to its preoperative
      level. Urethral sphincter dysfunction is considered the main factor for urinary
      incontinence after RARP.

PMID- 25863843
TI  - Shoulder instability: A myriad of decisions for optimal emergency department
      care.

PMID- 25863844
TI  - Fluoride and aluminium disturb neuronal morphology, transport functions,
      cholinesterase, lysosomal and cell cycle activities.
AB  - Fluoride and aluminium have been reported to cause severe alterations in the
      brain. However, their exact mechanisms of neurotoxic activities remain unknown.
      AIM: This study was designed to investigate the role of fluoride and aluminium in
      neuronal transport, lysosomal, cell cycle protein and acetylcholinesterase
      activities. METHOD: Adult Wistar rats were given low and high doses of fluoride,
      aluminium and a combination of both with the control group receiving distilled
      water for 30 days. Blood sera and brain homogenates were quantified for alkaline
      phosphatase (biomarker for neuronal transport) activities. Brain sections were
      stained with cresyl fast violet to detect neuronal cell damage. Histochemical
      demonstration of acetylcholinesterase (AChE) activity and the immunohistochemical
      detection of cell cycle protein (anti-cyclin D) and lysosomal protein (anti
      cathepsin D) were done using the antigen retrieval method. RESULT: Results showed
      severe histomorphologic alterations, dysregulation of membrane transport
      activities, inhibition of AChE activities and increased expression of lysosomal
      and cell cycle proteins. CONCLUSION: These findings confirm that excessive
      fluoride and aluminium intake induces the progression of cell death which inhibit
      AChE activities and trigger the release of lysosomal and cell cycle proteins.

PMID- 25863845
TI  - The geographic distribution of optometrists in Ontario.

PMID- 25863847
TI  - Prospective randomized trial: outcomes of SF6 versus C3F8 in macular hole
      surgery.
AB  - OBJECTIVE: To compare macular hole (MH) closure and visual acuity improvement
      after vitrectomy using SF6 versus C3F8 gas tamponade. The secondary purposes were
      to report the cumulative incidence of cataract development at 1 year after MH
      surgery and the proportion of complications. DESIGN: Prospective, randomized
      study. PARTICIPANTS: Thirty-one patients were prospectively randomized to the SF6
      group and 28 patients to the C3F8 group. METHODS: Preoperative data included MH
      minimum diameter, Early Treatment Diabetic Retinopathy Study (ETDRS) best
      corrected visual acuity (BCVA), cataract staging, and intraocular pressure (IOP)
      measurement. Postoperative data included optical coherence tomography
      confirmation of the closure at 6 weeks and 1 year, and ETDRS BCVA and cataract
      development/extraction, both 1 year after the MH surgery. RESULTS: Primary MH
      closure was achieved in 93.3% in the SF6 group and 92.9% in the C3F8 group. Mean
      ETDRS BCVA improved by 17.7 letters in the SF6 and 16.9 letters in the C3F8
      group. The difference in cumulative incidence of cataract development and
      extraction between both groups was not statistically significant. Regardless of
      the dye used, similar results were achieved. Finally, the proportion of adverse
      events was similar in both groups. CONCLUSIONS: MH surgery with SF6 gas achieves
      results similar to C3F8 in terms of visual acuity improvement, MH closure,
      cataract development/extraction, and adverse events.

PMID- 25863848
TI  - SUNDROP: six years of screening for retinopathy of prematurity with telemedicine.
AB  - OBJECTIVE: To report the 6-year results of the Stanford University Network for
      Diagnosis of Retinopathy of Prematurity (SUNDROP) initiative in the context of
      telemedicine screening initiatives for retinopathy of prematurity (ROP). DESIGN:
      A retrospective analysis. PARTICIPANTS: Premature newborns requiring ROP
      screening at 6 neonatal intensive care units from December 1, 2005, to November
      30, 2011. METHODS: Infants were evaluated via remote retinal photography by an
      ROP specialist. A total of 608 preterm infants meeting ROP examination criteria
      were screened with the RetCam II/III (Clarity Medical Systems, Pleasanton,
      Calif.). Primary outcomes were treatment-warranted ROP (TW-ROP) and adverse
      anatomical events. RESULTS: During the 6 years, 1216 total eyes were screened
      during 2169 examinations, generating 26 970 retinal images, an average of 3.56
      examinations and 44.28 images per patient. Twenty-two (3.6%) of the infants
      screened met criteria for TW-ROP. Compared with bedside binocular ophthalmoscopy,
      remote interpretation of RetCam II/III images had a sensitivity of 100%,
      specificity of 99.8%, positive predicative value of 95.5%, and negative
      predicative value of 100% for the detection of TW-ROP. No adverse anatomical
      outcomes were observed for any enrolled patient. CONCLUSIONS: The 6-year results
      for the SUNDROP telemedicine initiative were highly favourable with respect to
      diagnostic accuracy. Telemedicine appears to be a safe, reliable, and cost
      effective complement to the efforts of ROP specialists, capable of increasing
      patient access to screening and focusing the resources of the current ophthalmic
      community on infants with potentially vision-threatening disease.

PMID- 25863849
TI  - Evaluation and neuroimaging of the Horner syndrome.
AB  - OBJECTIVE: To define the efficacy, safety, and cost-effectiveness of a single
      centre's approach to evaluating Horner syndrome (HS) including a simplified
      single neuroimaging protocol. DESIGN: Case series study. PARTICIPANTS: Medical
      records of 34 patients diagnosed with HS at Houston Methodist Hospital (HMH) were
      reviewed after obtaining Institutional Review Board approval. METHODS: A
      retrospective chart review was performed for all patients presenting with the
      diagnosis of HS at the HMH from January 2010 to November 2013. All patients had
      diagnostic imaging with contrast-enhanced brain magnetic resonance imaging (MRI)
      extending to the T2 level in the chest. They had either documented causative
      diagnosis for HS or were "idiopathic." Efficacy and cost-effectiveness of the
      proposed neuroimaging technique were analyzed compared with other recommended
      protocols. RESULTS: We initially reviewed 34 charts with presumed diagnosis of
      HS; 27 charts were included in the analysis. The average age of patients was 46.6
      years. Eleven patients (41%) had a final diagnosis of HS secondary to a proven
      cause, and 16 patients (59%) were diagnosed as "idiopathic." Ten patients (63%)
      in the idiopathic group had follow-up, and none of those with follow-up had an
      alternative cause. The estimated cost of our recommended MRI protocol was
      US$667.76 without magnetic resonance angiography (MRA) or US$1501.71 with MRA.
      CONCLUSIONS: A single contrast-enhanced brain MRI extending to the T2 level in
      the chest is an effective and simple means of ruling out life-threatening and
      other causative factors of HS. Compared with previous imaging recommendations,
      this proposed protocol may be simpler for clinicians to use and more cost
      effective.

PMID- 25863850
TI  - Improvement of retinal function in L-ORD after prolonged dark adaptation.
AB  - OBJECTIVE: To describe the changes in dark-adapted (DA) retinal
      electrophysiological function after prolonged dark adaptation in a cohort of
      patients with late-onset retinal degeneration (L-ORD). DESIGN: Prospective case
      series. PARTICIPANTS: Nine patients with either stage 2 or 3 L-ORD. METHODS:
      International Society for Clinical Electrophysiology of Vision standard DA
      electroretinograms (ERGs) were performed before and after a period of extended
      dark adaptation (16 hours) in a cohort of patients heterozygous for the Ser163Arg
      mutation in C1QTNF5. RESULTS: Rod function was abnormal in 8 of 9 patients after
      standard (20 min) of dark adaptation. After extended dark adaptation, rod
      function normalized in 4 patients and there was a mean improvement in the DA 0.01
      rod-specific ERG b-wave amplitude of 310% (p = 0.004). A significant improvement
      in DA 3.0 a-wave ERG amplitude localized the improvement in rod function at the
      level of the photoreceptor. CONCLUSIONS: This study demonstrates that a
      significant proportion of rod dysfunction in L-ORD can be reversed by extended
      dark adaptation and suggests that an abnormality of the visual cycle contributes
      to the pathogenesis of the disease. These findings would suggest that some
      retinal function could be restored, even in advanced cases of the disease if a
      suitable treatment is found.

PMID- 25863851
TI  - Socioeconomic factors associated with visual impairment and ophthalmic care
      utilization in patients with type II diabetes.
AB  - OBJECTIVE: To examine the association between socioeconomic factors and
      ophthalmic care services/visual impairment among patients with diabetes. DESIGN:
      Data from the Survey on Living with Chronic Disease in Canada (SLCDC)-Diabetes
      Component 2011 were used. PARTICIPANTS: A cross-sectional, nationally
      representative sample of patients with diabetes weighted to represent the
      civilian, noninstitutionalized Canadian population with self-reported type II
      diabetes. METHODS: Socioeconomic factors were classified into predictive factors,
      need, and non-need factors. Factors associated with the ophthalmic care
      utilization and visual impairment were assessed using logistic regression models,
      weighted for the SLCDC sampling strategy. RESULTS: Among all patients with type
      II diabetes, factors associated with increased eye screening were: (i) discussion
      of diabetic complications with health professionals (odds ratio [OR] 2.02, 95% CI
      1.28-3.19); (ii) having private insurance (OR 3.23, 95% CI 2.21-4.73); and (iii)
      duration of diabetes longer than 10 years (OR 1.53, 95% CI 1.04-2.25). Among
      asymptomatic patients (those who reported having no visual impairment), patients
      with lower income had 40% decreased odds of having eye screening services
      compared with those with higher income (OR 0.60, 95% CI 0.37-0.98). Among all
      patients with type II diabetes, visual impairment was more likely in females (OR
      1.53, 95% CI 1.12-2.09), older patients (OR 18.12, 95% CI 6.63-49.51), and those
      with poor self-rated health (OR 3.10, 95% CI 1.62-5.96). CONCLUSIONS: Our study
      found that interactions between health professionals and patients, as well as
      having private health insurance, were the main factors associated with ophthalmic
      resource utilization, whereas age, sex, duration of diabetes, and self-rated
      health were associated with visual impairment in patients with type II diabetes.

PMID- 25863852
TI  - Repeated intravitreal anti-vascular endothelial growth factor injections can
      induce iatrogenic ocular hypertension, especially in patients with open-angle
      glaucoma.
AB  - OBJECTIVE: To report the rate of intraocular pressure (IOP) elevation after
      repeated intravitreal injections (IVIs) of anti-vascular endothelial growth
      factor (anti-VEGF) agents and to determine the risk factors. METHODS: A total of
      193 patients (217 eyes) undergoing ranibizumab (n = 196) or bevacizumab (n = 21)
      IVIs were prospectively examined. The incidence of ocular hypertension (OHT)
      after these injections was investigated with respect to the number of injections,
      pre-existing open-angle glaucoma, diabetes, YAG capsulotomy, age, and sex.
      RESULTS: A total of 1461 IVIs was performed. After a mean of 6.7 +/- 7.1 IVIs
      (range, 1-49), 4.6% (n = 10) had IOP elevation more than 25 mm Hg and required
      medical treatment (1.4% of them spiked above 30 mm Hg). Patients with pre
      existing glaucoma experienced higher prevalence of OHT (12.9%) and greater rates
      than the control group (19.6 +/- 5.7 mm Hg vs 16.4 +/- 3.9 mm Hg, p < 0.001). No
      significant difference was found in the diabetes subgroup (n = 66, p = 0.62) or
      in the YAG capsulotomy subgroup (n = 24, p = 0.51) compared with the control
      group. The IOP peak was significantly correlated with the total number of IVIs (p
      = 0.0002, r = 0.25). CONCLUSIONS: Serial IVIs may lead to persistent IOP
      elevation that requires IOP-lowering therapy. The risk is correlated with the
      number of injections and increases in the glaucoma population, and must be
      checked during follow-up.

PMID- 25863853
TI  - Topical glaucoma therapy and ocular surface disease: a prospective, controlled
      cohort study.
AB  - OBJECTIVE: To evaluate the association between the intensity and duration of
      glaucoma topical therapy and severity of signs and symptoms of ocular surface
      disease (OSD). DESIGN: Single-site, prospective, controlled, cross-sectional
      study. PARTICIPANTS: Sixty-one patients with no diagnosis of or previous
      treatment for OSD were identified. METHODS: Patients were assigned to 2 groups:
      the glaucoma group with 31 patients diagnosed with primary open-angle glaucoma
      and using at least 1 topical intraocular pressure (IOP)-lowering medication and
      the control group including 30 patients with no diagnosis of glaucoma or history
      of topical therapy usage. The right eye of each patient was arbitrarily chosen.
      Each patient completed an Ocular Surface Disease Index (OSDI) questionnaire and
      underwent evaluation of the ocular surface by conjunctival and corneal lissamine
      green (LG) staining and tear breakup time (TBUT). The intensity index (drops/wk *
      therapy duration in years) was calculated to quantify the topical therapy.
      RESULTS: OSDI scores of the glaucoma group correlated to the intensity index (r =
      0.46, CI 0.13-0.69). The glaucoma group had a higher mean OSDI score than the
      control group (18.97 +/- 9.5 versus 6.25 +/- 5.7, p = 5.85E-08). Abnormal TBUT
      and LG staining scores were prevalent in the glaucoma group compared with the
      control group (68% vs 17%, p = 0.000078; 65% vs 3%, p = 2.9E-07). CONCLUSIONS:
      Patients on glaucoma therapy have a greater prevalence of OSD symptoms, and their
      intensity index correlates to the OSDI score. The intensity index reflects
      quantitatively the amount of treatment and can be further validated in future
      studies as a predicting tool for OSD development.

PMID- 25863854
TI  - Characteristics of patients with ocular cicatricial pemphigoid referred to major
      tertiary hospital.
AB  - OBJECTIVE: To evaluate the demographic and clinical characteristics of patients
      referred to a tertiary care hospital cornea clinic for ocular cicatricial
      pemphigoid (OCP) assessment. DESIGN: Retrospective, nonrandomized, consecutive
      case series. PARTICIPANTS: Thirty three patients with OCP who were treated at the
      corneal clinic of Toronto Western Hospital from 2003 to 2012. METHODS: Database
      search of patients from 2003 to 2012 with a referral request or diagnosis of OCP
      was conducted at a tertiary care hospital cornea clinic. Charts of 33 patients
      (64 eyes) were reviewed. Outcome measures included patient demographics, methods
      of diagnosis, visual acuity, ocular features, and disease staging using Foster's
      staging system, systemic modes of treatment, disease progression, and presence of
      systemic involvement. RESULTS: Mean patient age at presentation was 69.8 years
      (range 40-91), and 81% (27/33) were female. At presentation, disease staging
      consisted of stage I (subepithelial fibrosis) 7.8% (5/64), stage II (shortened
      fornices) 21.8% (14/64), stage III (symblepharon formation) 65.6% (42/64), and
      stage IV (keratinization with or without globe immobility) 4.6% (3/64). At the
      final follow-up visit, the proportions of the involved eyes for stages I to IV
      were 1.5% (1/64), 10.9% (7/64), 76.5% (49/64), and 10.9% (7/64), respectively.
      Conjunctival biopsies were obtained from 81% (27/33) of patients and reported as
      positive in 30% (8/27), negative in 63% (17/27), and inconclusive in 7% (2/27) of
      patients. Mean duration of follow-up was 6.8 +/- 5.6 years (range 0.5-22), and
      66.6% (22/33) of patients had progressive disease. Systemic mucocutaneous
      involvement was noted in 36.3% (12/33) of patients. CONCLUSIONS: The high rate of
      disease progression suggests the need for improved therapeutic options.
      Additional modalities are needed in addition to conjunctival biopsy to confirm a
      diagnosis of OCP in patients with clinical signs of the disease.

PMID- 25863855
TI  - Corneal collagen cross-linking for keratoconus: results of 3-year follow-up in
      Pakistani population.
AB  - OBJECTIVE: To assess the effectiveness and safety of corneal collagen cross
      linking with riboflavin and ultraviolet A (UV-A) light in arresting the
      progression of keratoconus. DESIGN: Prospective, nonrandomized experimental
      study. PARTICIPANTS: Seventy-one eyes of 66 patients with progressive
      keratoconus. METHODS: Corneal cross-linking was carried out with riboflavin and
      UV-A light in patients with progressive keratoconus at Al-Shifa Trust Eye
      Hospital, Pakistan. Standard protocol of cross-linking comprising epithelial
      debridement, instillation of isotonic riboflavin (0.1%) for 30 minutes, followed
      by application of UV-A light for 30 minutes with riboflavin was followed.
      Variables of interest were uncorrected and best corrected visual acuity (BCVA)
      with spectacles, spherical equivalent refraction, maximum keratometric reading,
      and central corneal thickness. Three-year results of these variables after cross
      linking were analyzed. RESULTS: Mean age of patients was 19.79 +/- 3.71 years;
      75.8% were male and 24.2% were female. After 3 years, uncorrected visual acuity
      improved in 31.0% by mean 2.0 +/- 1.06 Snellen lines, remained same in 64.8%, and
      deteriorated in 4.2% by mean 1.33 +/- 0.57 lines. BCVA improved in 56.3% by mean
      2.37 +/- 1.10 Snellen lines, remained the same in 40.8%, and deteriorated in 2.8%
      by mean 1.50 +/- 0.70 lines. Spherical equivalent refraction decreased in 33.8%
      by mean 2.29 +/- 1.48 D, remained stable in 60.6%, and increased in 5.6% by mean
      1.43 +/- 0.42 D. Maximum keratometric reading showed mean regression of 2.64 +/-
      1.42 D in 60.6%, stabilization in 35.2%, and mean progression of 2.0 +/- 0.17 D
      in 4.2%. In 95.8% of cases, progression of keratoconus halted. Central corneal
      thickness was decreased by mean 10.32 +/- 21.19 um. CONCLUSIONS: Cross-linking is
      an effective and safe treatment option in halting the progression of keratoconus.

PMID- 25863856
TI  - Hydroxyapatite versus polyethylene orbital implants for patients undergoing
      enucleation for uveal melanoma.
AB  - OBJECTIVE: Clinical outcomes for enucleation vary widely, depending on surgical
      technique, implant choice, and indications for enucleation. The goal of this
      study was to compare complications of enucleation using hydroxyapatite versus
      polyethylene orbital implants for 1 indication: uveal melanoma in adults. DESIGN:
      Retrospective chart review PARTICIPANTS: Consecutive case series of patients who
      were enucleated for uveal melanoma by a single surgeon (J.W.H.) from 1999-2009.
      METHODS: A retrospective chart review was performed to record clinical and
      histopathologic features, surgical technique, orbital implant characteristics,
      and outcomes in a consecutive series of patients with uveal melanoma who were
      treated by enucleation by a single surgeon (J.W.H.) between 1999 and 2009.
      RESULTS: This study included 139 patients; 64 received hydroxyapatite implants,
      and 75 received polyethylene implants wrapped in donor sclera. Complications
      included blepharoptosis in 4 (2.9%), conjunctival cyst in 2 (1.4%), volume
      deficit in 2 (1.4%), implant exposure in 1 (0.7%), and conjunctival erosion in 1
      (0.7%) patient. There were no significant differences in the clinicopathologic
      features or complications between the 2 groups. CONCLUSIONS: Few complications
      were encountered using this enucleation technique, and there was no difference in
      complication rates between patients receiving hydroxyapatite and polyethylene
      implants.

PMID- 25863857
TI  - Nailfold capillaroscopy assessment in patients with glaucoma with a current optic
      disc hemorrhage.
AB  - OBJECTIVE: To determine whether there is an increased prevalence of nailfold
      hemorrhages in patients with glaucoma with a current optic disc hemorrhage (ODH)
      compared with those without a history of ODH. DESIGN: Prospective observational
      study. PARTICIPANTS: Group 1 (n = 40) consisted of patients with primary open
      angle glaucoma or normal tension glaucoma (POAG/NTG) with a current ODH who met
      the specified inclusion/exclusion criteria. Group 2 (n = 20) consisted of age-
      and sex-matched patients with glaucoma without a history of ODH who met specified
      criteria (control group). METHODS: This study was performed in a clinical
      practice setting. Nailfold capillaroscopy was performed in each participant to
      determine the presence of nailfold hemorrhages and other capillary morphologic
      changes. RESULTS: There was no significant difference in mean age (68 +/- 10
      years for Group 1 vs 71 +/- 12 years for Group 2; p = 0.20) or sex (62% female in
      Group 1 vs 59% female in Group 2; p = 0.80) between the groups. There was no
      significant difference in the proportion of patients with nailfold hemorrhage(s)
      between Group 1 (23%, 10/42) and Group 2 (26%, 11/42; p = 0.8). Subanalysis of
      Group 1 identified no significant difference in the prevalence of nailfold
      hemorrhages between patients with POAG (23%, 6/26) and NTG (25%, 4/16; p = 0.9).
      CONCLUSIONS: We report no increase in nailfold haemorrhages in patients with
      glaucoma with a current ODH compared with patients with glaucoma without a
      history of ODH. However, the prevalence of nailfold hemorrhages in patients with
      glaucoma either with or without an ODH is significantly greater than that
      identified in normal (nonglaucoma) control subjects in other studies.

PMID- 25863858
TI  - Changes in retinal oxygen saturation, choroidal thickness, and retinal nerve
      fibre layer.
AB  - OBJECTIVE: To investigate the changes of retinal oxygen saturation (Sat O2)
      concentrations, choroidal thickness (CT), and retinal nerve fibre layer (RNFL) in
      eyes with trabeculectomy-required acute primary angle closure (APAC). DESIGN:
      Prospective, longitudinal study. PARTICIPANTS: Twenty-three eyes with
      trabeculectomy-required APAC were recruited. METHODS: Retinal oximetry was
      performed at postoperative day one and again at approximately 1 month. CT and the
      RNFL were tested on the same day. A paired t test and Pearson correlation were
      used for analysis. RESULTS: Mean Sat O2 increased in retinal arterioles from
      88.74% +/- 14.36% at postoperative day 1 to 96.61% +/- 18.42% at 1 month (p =
      0.049). The mean diameter of the arterioles was statistically different between
      postoperative day 1 and 1 month (p = 0.044), as was the mean diameter of the
      venules (p = 0.027). APAC eyes at postoperative 1 month had a thinner mean CT,
      compared with day 1 (p = 0.002). No significant difference was found in the RNFL
      between postoperative day 1 and 1 month (p > 0.05). The Sat O2 in retinal
      arterioles correlated with the mean diameter of the arterioles at postoperative
      day 1 (r = -0.482, p = 0.020) and at 1 month (r = -0.463, p = 0.026). No
      significant correlation was found between retinal Sat O2 and other parameters.
      CONCLUSIONS: Increased Sat O2 in retinal arterioles, changed vessel diameter, and
      thinner CT from postoperative day 1 to 1 month suggest gradual recovery from
      APAC. However, the different pathophysiologies for APAC still need further study
      to prove.

PMID- 25863859
TI  - Comparison between fullfield electroretinography obtained from handheld and
      tabletop devices in normal subjects.
AB  - OBJECTIVE: To compare full-field electroretinography (ERG) parameters obtained
      from Ephios handheld and VERIS tabletop ERG devices in normal subjects for
      interchangeable usability and reliability. DESIGN: Comparison study.
      PARTICIPANTS: Comparison of full-field ERG between two devices for 57 normal
      subjects. METHODS: ERG was recorded for 57 normal subjects using tabletop device
      (VERIS 5.2.2X; Electro-Diagnostic Imaging Inc, San Mateo, Calif.) and handheld
      ERG device (Ephios handheld portable ERG system; ephios ab; Teknikringen,
      Linkoping, Sweden). Bland-Altman plot was done to measure the agreement between
      the 2 devices. Intraclass correlation coefficient (ICC) was calculated for
      amplitudes, implicit times, and b/a ratio to assess the reliability. Coefficient
      of variation (CV = 100 * [standard deviation/mean]) with 95% CI was calculated to
      measure the variability between the devices. Wilcoxon sign rank test was used to
      assess the repeatability of the Ephios handheld device. RESULTS: The mean a-wave
      and b-wave amplitudes of dark-adapted 3.0 ERG for the tabletop were 220.3 +/-
      52.6 and 471.5 +/- 84.3 MUV, respectively, whereas the mean a-wave and b-wave
      amplitudes in the same scotopic setting for the handheld device were 152.6 +/-
      34.2 and 379.7 +/- 75.9 MUV, respectively. The values represent mean +/- standard
      deviation. The ICC of b/a ratio was 0.660 between the devices. The amplitudes CV
      of tabletop and handheld ERG devices ranged from 17.9% to 29.1% and from 22.4% to
      30.1%, respectively. CONCLUSIONS: The pattern of waveform of the Ephios handheld
      device is similar to the VERIS tabletop device. The ERG parameters showed
      variability between the 2 devices. Hence Ephios handheld ERG device can be used
      along with its normative data for measuring ERG. Because of variability, the
      devices cannot be used interchangeably.

PMID- 25863860
TI  - Natural course of vitreomacular traction syndrome observed by spectral-domain
      optical coherence tomography.
AB  - OBJECTIVE: Our study aimed to characterize the natural course of vitreomacular
      traction (VMT) syndrome, on which discrepancies have been reported in previous
      publications, by spectral-domain optical coherence tomography (SD-OCT). DESIGN:
      Retrospective chart review. PARTICIPANTS: A total of 23 eyes of 23 patients with
      idiopathic symptomatic VMT syndrome diagnosed and followed up in Peking Union
      Medical College Hospital from 2008 to 2013. METHODS: Clinical records of all
      patients who underwent SD-OCT examination and were diagnosed and followed up as
      idiopathic VMT syndrome were reviewed. Those who had at least 2 visits were
      included. The median observation period of the patients was 8.2 +/- 7.9 months.
      RESULTS: The 23 eyes were categorized into 3 groups based on the follow-up
      results of SD-OCT: the posterior vitreous detachment (PVD) group comprised 4 eyes
      that developed complete PVD, the full-thickness macular hole (FMH) group included
      4 eyes that formed FMH, and the persisted VMT (PVMT) group comprised the other 15
      eyes with PVMT. Epiretinal membrane (ERM) persisted in all 5 eyes in the PVMT
      group. FMH occurred in 3 of 7 eyes with outer lamellar macular hole (LMH) at the
      first visit. CONCLUSIONS: Spontaneous development of complete PVD in VMT syndrome
      during follow-up appeared to be more common in our study than in previous reports
      without SD-OCT. Persistence of ERM might be an unfavourable prognostic factor in
      the natural course of VMT syndrome. The outer LMH might be a risk factor for FMH
      formation.

PMID- 25863861
TI  - Is it possible to predict the postoperative visual outcome before epiretinal
      membrane removal?

PMID- 25863862
TI  - Authors' reply.

PMID- 25863863
TI  - Aneurysmal bone cyst with fibrous dysplasia resulting in partial third nerve
      palsy.

PMID- 25863864
TI  - Modified tennis ball-induced ocular trauma.

PMID- 25863865
TI  - Rathke cleft cyst presenting as unilateral progressive oculomotor nerve palsy.

PMID- 25863866
TI  - Degeneration of Axenfeld nerve loop: a clinicopathologic case report.

PMID- 25863867
TI  - The role of endoscopy in the management of GERD.
AB  - We recommend that uncomplicated GERD be diagnosed on the basis of typical
      symptoms without the use of diagnostic testing, including EGD. We recommend EGD
      for patients who have symptoms suggesting complicated GERD or alarm symptoms. We
      recommend that EGD not be routinely performed solely for the assessment of
      extraesophageal GERD symptoms. We recommend that endoscopic findings of reflux
      esophagitis be classified according to an accepted grading scale or described in
      detail. We suggest that repeat EGD be performed in patients with severe erosive
      esophagitis after at least an 8-week course of PPI therapy to exclude underlying
      BE or dysplasia. 44BB We recommend against obtaining tissue samples from
      endoscopically normal tissue to diagnose GERD or exclude BE in adults. We suggest
      that endoscopy be considered in patients with multiple risk factors for Barrett's
      esophagus. We recommend that tissue samples be obtained to confirm endoscopically
      suspected Barrett's esophagus. We suggest that endoscopic antireflux therapy be
      considered for selected patients with uncomplicated GERD after careful discussion
      with the patient regarding potential adverse effects, benefits, and other
      available therapeutic options.

PMID- 25863869
TI  - Forum on the Brain and Hearing Aids.
AB  - PURPOSE: The purpose of this article is to introduce and provide an overview of
      the 3 articles presented in the invited forum "The Brain and Hearing Aids."
      METHOD: The main ideas of the articles presented by the 3 panelists are
      identified, and a commentary is provided to synthesize the ideas. CONCLUSIONS:
      Benefits from hearing aids and auditory training entail higher-level cortical and
      cognitive processing involved in categorizing and remembering sound. New
      approaches to predicting, designing, and evaluating technological and behavioral
      interventions will need to consider the brain and not just the ears of listeners.

PMID- 25863868
TI  - Accurate membrane tracing in three-dimensional reconstructions from electron
      cryotomography data.
AB  - The connection between the extracellular matrix and the cell is of major
      importance for mechanotransduction and mechanobiology. Electron cryo-tomography,
      in principle, enables better than nanometer-resolution analysis of these
      connections, but restrictions of data collection geometry hamper the accurate
      extraction of the ventral membrane location from these tomograms, an essential
      prerequisite for the analysis. Here, we introduce a novel membrane tracing
      strategy that enables ventral membrane extraction at high fidelity and
      extraordinary accuracy. The approach is based on detecting the boundary between
      the inside and the outside of the cell rather than trying to explicitly trace the
      membrane. Simulation studies show that over 99% of the membrane can be correctly
      modeled using this principle and the excellent match of visually identifiable
      membrane stretches with the extracted boundary of experimental data indicates
      that the accuracy is comparable for actual data. 

PMID- 25863870
TI  - Assessment in steroid trial for IgG4-related sclerosing cholangitis.
AB  - PURPOSE: Response to steroids is included in the diagnostic criteria for IgG4
      related sclerosing cholangitis (IgG4-SC). To assess how to appropriately conduct
      steroid trials for IgG4-related SC, we examined the clinical pictures of steroid
      responsiveness in IgG4-SC patients. MATERIAL AND METHODS: A total of 29 patients
      with IgG4-SC (lower bile duct involvement, n=29; hilar/intrahepatic bile duct
      involvement, n=6) initially treated with steroids were enrolled in this study.
      Blood biochemistry was examined at about 5, 10 and 15 days after commencing
      steroid therapy. Endoscopic retrograde cholangiography (ERC) and magnetic
      resonance cholangiopancreatography (MRCP) were performed after steroid
      administration in 18 and 25 patients, respectively. RESULTS: In 19 patients
      without biliary drainage, elevated serum levels of total bilirubin, alanine
      aminotransferase, and alkaline phosphatase were halved in 50%, 25%, and 44% of
      patients at about 5 days after starting steroids, and in 17%, 38%, and 44% at
      about 10 days. Responsiveness to steroids could be evaluated at 1-2 weeks on ERC
      or MRCP, but response was lower in the hilar/intrahepatic bile duct than in the
      lower bile duct. CONCLUSIONS: Steroid responsiveness of IgG4-SC is recommended to
      be assessed by blood biochemistry at 5 and 10 days and on MRCP and/or ERC at 1-2
      weeks after starting steroid.

PMID- 25863871
TI  - Complications associated with 9-10Fr venous access port use in adjuvant
      intraperitoneal chemotherapy after a cytoreductive surgery in ovarian cancer
      patients.
AB  - PURPOSE: To determine the complication rate associated with using a single-lumen
      intravenous access port with a silicone catheter of 9-10Fr size in the
      intraperitoneal treatment, including hyperthermic intraperitoneal chemotherapy,
      in ovarian cancer. PATIENTS/METHODS: We reviewed 27 patients who had subcutaneous
      venous access ports placed for the administration of IP chemotherapy. With four
      patients, the catheter was implanted during a hyperthermic intraperitoneal
      chemotherapy-related laparotomy using the closed technique. Each case was
      categorized as to the number of cycles of IP therapy received. RESULTS: Seven
      catheter-related complications were noted. These were divided into two
      categories: six malfunctions (24%) and one infection (4%). Overall, of the
      patients who had IP catheters placed and received IP chemotherapy, 13 (54.2%)
      were able to complete the six regimens. Among the four (14.8%) patients who had
      the catheters planted directly following the HIPEC, one experienced a catheter
      leak, one an infection and one concluded the treatment successfully; one is still
      being treated. CONCLUSIONS: A subcutaneous single-lumen intravenous access port
      with a silicone catheter of a large size (9-10Fr) is related to a lower rate of
      catheter-related complications than previously reported open-ended Tenckhoff
      catheter treatment. An additional advantage is the possibility of removing the
      catheter as an office procedure under local anesthesia. Intraperitoneal
      chemotherapy following a HIPEC procedure may cause increased occurrence of
      catheter-related complications. As of 2010 we have been using silicone
      subcutaneous catheters in our center.

PMID- 25863872
TI  - Effect of dietary supplementation on lipid photooxidation in beef meat, during
      storage under commercial retail conditions.
AB  - The effects of feeding composition on the photosensitized oxidation of lipids
      from beef meat, were evaluated during storage under commercial retail conditions.
      Feeding was enriched with linseed oil (LO), Dl-alpha tocopheryl acetate (vE) and
      conjugated linoleic acid (CLA) at different doses and provided for diverse
      periods, resulting in 7 diet groups (A-G). After slaughtering and 2 weeks of
      holding period, meat slices were packed in vessels with transparent shrink film
      and exposed to white fluorescent light for 8h at 8  degrees C. Total cholesterol
      oxidation products (COPs) level varied from 4.0 to 13.0 MUg/g of lipids, which
      corresponded to 0.1-0.6% oxidized cholesterol. The lowest peroxide value (PV) was
      found in the diet added with vE and LO for 90 days. Light exposure only had a
      significant impact on thiobarbituric acid reactive substances (TBARs). In
      general, Dl-alpha tocopheryl acetate supplemented for 90 days improved the
      oxidative stability of beef meat stored under commercial retail conditions.

PMID- 25863873
TI  - The posterior shift anticipatory postural adjustment in choice reaction step
      initiation.
AB  - The ability to step quickly in response to a perturbation has been shown to be
      critical for prevention of falls. The cognitive processing, weight shifting, and
      locomotion must be well timed to execute a successful step. The purpose of this
      study was to compare the response preparation and response execution processes
      between a simple (SRST) and a choice reaction stepping task (CRST). Nine healthy
      young subjects were recruited to participate in this study. Subjects were
      required to stand on a forceplate and maintain their balance, and step forward on
      a second forceplate with either the left or right foot after hearing an auditory
      tone. The center of pressure (COP) was analyzed to determine the types of
      anticipatory postural adjustment (APA) prior to a step. The APA phase and
      stepping phase timing was calculated based on the COP trajectory. Findings showed
      that reaction time (RT), APA phase and overall stepping latency were slower for
      CRST than for SRST. We also identified an intermediate type of APA response
      (posterior shift APA) in addition to the correct and error APA response, and
      found the posterior shift APA response had the fastest execution time for CRST,
      and may be beneficial for falls prevention. 

PMID- 25863874
TI  - Groove pancreatitis or Paraduodenal pancreatitis: what's in a name?

PMID- 25863875
TI  - Ruptured anterior mediastinal teratoma with radiologic, pathologic, and
      bronchoscopic correlation.
AB  - While most teratomas are asymptomatic, intrathoracic teratomas can rarely rupture
      spontaneously causing more alarming symptoms. Ruptured teratoma is a serious
      clinical entity, and early recognition is crucial for avoidance of further
      complications and preparation of proper surgical approach. We present a case of
      ruptured anterior mediastinal teratoma with radiologic, pathologic, and
      bronchoscopic correlation. This case uniquely illustrates a patient presenting
      with signs of infection and progressively worsening symptoms, thus emphasizing
      the need for early diagnosis and the importance of imaging. 

PMID- 25863876
TI  - Loss of renal India ink artifact-a useful radiological sign for obstructive
      hydronephrosis in pregnancy.
AB  - Magnetic resonance imaging is a useful tool for investigating causes of abdominal
      pain in pregnancy. Differentiating between physiologic hydronephrosis of
      pregnancy and pathologic hydronephrosis can be challenging for clinicians and
      radiologists. This report describes loss of the India ink artifact around the
      obstructed kidney as a novel and potentially useful radiological sign, which may
      be of value in the evaluation of abdominal pain and hydronephrosis in pregnancy. 

PMID- 25863877
TI  - West Nile virus adaptation to ixodid tick cells is associated with phenotypic
      trade-offs in primary hosts.
AB  - West Nile virus (WNV; Flaviviridae, Flavivirus) is the most geographically
      widespread arthropod-borne virus (arbovirus) in the world and is found in
      multiple ecologically distinct settings. Despite the likelihood of frequent
      exposure to novel hosts, studies evaluating the capacity and correlates of host
      range expansions or shifts of WNV and other arboviruses are generally lacking. We
      utilized experimental evolution of WNV in an Amblyomma americanum tick cell line
      to model an invertebrate host shift and evaluate the adaptive potential of WNV
      outside of its primary transmission cycle. Our results demonstrate that highly
      significant gains in replicative ability in ixodid tick cells are attainable for
      WNV but are also associated with widespread genetic change and significant
      phenotypic costs in vitro. Decreased fitness in primary hosts could represent a
      barrier to frequent exploitation of hard ticks by WNV in nature. 

PMID- 25863878
TI  - GBNV encoded movement protein (NSm) remodels ER network via C-terminal coiled
      coil domain.
AB  - Plant viruses exploit the host machinery for targeting the viral genome-movement
      protein complex to plasmodesmata (PD). The mechanism by which the non-structural
      protein m (NSm) of Groundnut bud necrosis virus (GBNV) is targeted to PD was
      investigated using Agrobacterium mediated transient expression of NSm and its
      fusion proteins in Nicotiana benthamiana. GFP:NSm formed punctuate structures
      that colocalized with mCherry:plasmodesmata localized protein 1a (PDLP 1a)
      confirming that GBNV NSm localizes to PD. Unlike in other movement proteins, the
      C-terminal coiled coil domain of GBNV NSm was shown to be involved in the
      localization of NSm to PD, as deletion of this domain resulted in the cytoplasmic
      localization of NSm. Treatment with Brefeldin A demonstrated the role of ER in
      targeting GFP NSm to PD. Furthermore, mCherry:NSm co-localized with ER-GFP
      (endoplasmic reticulum targeting peptide (HDEL peptide fused with GFP). Co
      expression of NSm with ER-GFP showed that the ER-network was transformed into
      vesicles indicating that NSm interacts with ER and remodels it. Mutations in the
      conserved hydrophobic region of NSm (residues 130-138) did not abolish the
      formation of vesicles. Additionally, the conserved prolines at positions 140 and
      142 were found to be essential for targeting the vesicles to the cell membrane.
      Further, systematic deletion of amino acid residues from N- and C-terminus
      demonstrated that N-terminal 203 amino acids are dispensable for the vesicle
      formation. On the other hand, the C-terminal coiled coil domain when expressed
      alone could also form vesicles. These results suggest that GBNV NSm remodels the
      ER network by forming vesicles via its interaction through the C-terminal coiled
      coil domain. Interestingly, NSm interacts with NP in vitro and coexpression of
      these two proteins in planta resulted in the relocalization of NP to PD and this
      relocalization was abolished when the N-terminal unfolded region of NSm was
      deleted. Thus, the NSm interacts with NP via its N-terminal unfolded region and
      the NSm-NP complex could in turn interact with the ER membrane via the C-terminal
      coiled coil domain of NSm to form vesicles that are targeted to PD and there by
      assist the cell to cell movement of the viral genome complex. 

PMID- 25863879
TI  - The vaccinia virus E6 protein influences virion protein localization during virus
      assembly.
AB  - Vaccinia virus mutants in which expression of the virion core protein gene E6R is
      repressed are defective in virion morphogenesis. E6 deficient infections fail to
      properly package viroplasm into viral membranes, resulting in an accumulation of
      empty immature virions and large aggregates of viroplasm. We have used immunogold
      electron microscopy and immunofluorescence confocal microscopy to assess the
      intracellular localization of several virion structural proteins and enzymes
      during E6R mutant infections. We find that during E6R mutant infections virion
      membrane proteins and virion transcription enzymes maintain a normal localization
      within viral factories while several major core and lateral body proteins
      accumulate in aggregated virosomes. The results support a model in which vaccinia
      virions are assembled from at least three substructures, the membrane, the
      viroplasm and a "pre-nucleocapsid", and that the E6 protein is essential for
      maintaining proper localization of the seven-protein complex and the viroplasm
      during assembly. 

PMID- 25863880
TI  - The minute virus of mice exploits different endocytic pathways for cellular
      uptake.
AB  - The minute virus of mice, prototype strain (MVMp), is a non-enveloped, single
      stranded DNA virus of the family Parvoviridae. Unlike other parvoviruses, the
      mechanism of cellular uptake of MVMp has not been studied in detail. We analyzed
      MVMp endocytosis in mouse LA9 fibroblasts and a tumor cell line derived from
      epithelial-mesenchymal transition through polyomavirus middle T antigen
      transformation in transgenic mice. By a combination of immunofluorescence and
      electron microscopy, we found that MVMp endocytosis occurs at the leading edge of
      migrating cells in proximity to focal adhesion sites. By using drug inhibitors of
      various endocytic pathways together with immunofluorescence microscopy and flow
      cytometry analysis, we discovered that MVMp can use a number of endocytic
      pathways, depending on the host cell type. At least three different mechanisms
      were identified: clathrin-, caveolin-, and clathrin-independent carrier-mediated
      endocytosis, with the latter occurring in transformed cells but not in LA9
      fibroblasts. 

PMID- 25863881
TI  - Cyhalofop-butyl has the potential to induce developmental toxicity, oxidative
      stress and apoptosis in early life stage of zebrafish (Danio rerio).
AB  - Cyhalofop-butyl is a selective herbicide widely employed in paddy field, which
      can transfer into aquatic environments. However, details of the environmental
      risk and aquatic toxicity of cyhalofop-butyl have not been fully investigated. In
      this study, zebrafish (Danio rerio) embryos were exposed to a range of cyhalofop
      butyl until 120 hour post-fertilization (hpf) to assess embryonic toxicity of the
      chemical. Our results demonstrated that cyhalofop-butyl was highly toxic to
      zebrafish embryos, with concentration-dependent negative effects in embryonic
      development. In addition, exposure to cyhalofop-butyl resulted in significant
      increases in reactive oxygen species (ROS) production and cell apoptosis in heart
      area. The mRNA levels of the genes related to oxidative stress and apoptosis were
      also altered significantly after cyhalofop-butyl exposure. Moreover, the activity
      of capspase-9 and caspase-3 were significantly increased. Therefore, we
      speculated that oxidative stress-induced apoptosis should be responsible for
      abnormal development during embryogenesis after cyhalofop-butyl exposure. 

PMID- 25863882
TI  - Arsenate reduction and mobilization in the presence of indigenous aerobic
      bacteria obtained from high arsenic aquifers of the Hetao basin, Inner Mongolia.
AB  - Intact aquifer sediments were collected to obtain As-resistant bacteria from the
      Hetao basin. Two strains of aerobic As-resistant bacteria (Pseudomonas sp. M17-1
      and Bacillus sp. M17-15) were isolated from the aquifer sediments. Those strains
      exhibited high resistances to both As(III) and As(V). Results showed that both
      strains had arr and ars genes, and led to reduction of dissolved As(V), goethite
      adsorbed As(V), scorodite As(V) and sediment As(V), in the presence of organic
      carbon as the carbon source. After reduction of solid As(V), As release was
      observed from the solids to solutions. Strain M17-15 had a higher ability than
      strain M17-1 in reducing As(V) and promoting the release of As. These results
      suggested that the strains would mediate As(V) reduction to As(III), and
      thereafter release As(III), due to the higher mobility of As(III) in most aquifer
      systems. The processes would play an important role in genesis of high As
      groundwater. 

PMID- 25863883
TI  - Chronic effects of six micro/nano-Cu2O crystals with different structures and
      shapes on Daphnia magna.
AB  - Six micro/nano-Cu2O crystals evolved from cubes to corner-truncated cubes, vertex
      truncated octahedrons and ultimately to octahedrons were synthesized in this
      work, and the chronic toxicity of these crystal suspensions (10 MUg L(-1)) for
      Daphnia magna was investigated over a 30-day period. Our results indicated that
      the octahedrons had the most evident toxic effect, but the cubes were minimally
      toxic. The mortality rate of the octahedral treatment was as high as 86.7%,
      whereas that of the cubic treatment was only 6.7%. Significant inhibitions in
      growth and reproduction were observed under octahedral exposure, with reduced
      impacts from vertex-truncated octahedrons, corner-truncated cubes, and cubic
      crystals. The chronic effects of different micro/nano-Cu2O crystals were related
      to their solubility in the gut of the organisms. The solubility of micro/nano
      Cu2O crystals was influenced by surface atomic arrangement and diverse surface
      activity. Thus, the structure and intestinal solubility of nanocrystals should be
      evaluated for long-term toxicity.

PMID- 25863884
TI  - An empirical inferential method of estimating nitrogen deposition to
      Mediterranean-type ecosystems: the San Bernardino Mountains case study.
AB  - The empirical inferential method (EIM) allows for spatially and temporally-dense
      estimates of atmospheric nitrogen (N) deposition to Mediterranean ecosystems.
      This method, set within a GIS platform, is based on ambient concentrations of
      NH3, NO, NO2 and HNO3; surface conductance of NH4(+) and NO3(-); stomatal
      conductance of NH3, NO, NO2 and HNO3; and satellite-derived LAI. Estimated
      deposition is based on data collected during 2002-2006 in the San Bernardino
      Mountains (SBM) of southern California. Approximately 2/3 of dry N deposition was
      to plant surfaces and 1/3 as stomatal uptake. Summer-season N deposition ranged
      from <3 kg ha(-1) in the eastern SBM to ~ 60 kg ha(-1) in the western SBM near
      the Los Angeles Basin and compared well with the throughfall and big-leaf
      micrometeorological inferential methods. Extrapolating summertime N deposition
      estimates to annual values showed large areas of the SBM exceeding critical loads
      for nutrient N in chaparral and mixed conifer forests.

PMID- 25863885
TI  - Seabirds, gyres and global trends in plastic pollution.
AB  - Fulmars are effective biological indicators of the abundance of floating plastic
      marine debris. Long-term data reveal high plastic abundance in the southern North
      Sea, gradually decreasing to the north at increasing distance from population
      centres, with lowest levels in high-arctic waters. Since the 1980s, pre
      production plastic pellets in North Sea fulmars have decreased by ~75%, while
      user plastics varied without a strong overall change. Similar trends were found
      in net-collected floating plastic debris in the North Atlantic subtropical gyre,
      with a ~75% decrease in plastic pellets and no obvious trend in user plastic. The
      decreases in pellets suggest that changes in litter input are rapidly visible in
      the environment not only close to presumed sources, but also far from land.
      Floating plastic debris is rapidly "lost" from the ocean surface to other as-yet
      undetermined sinks in the marine environment.

PMID- 25863886
TI  - Bioremediation of 1,2-dichloroethane contaminated groundwater: Microcosm and
      microbial diversity studies.
AB  - In this study, the effectiveness of bioremediating 1,2-dichloroethane (DCA)
      contaminated groundwater under different oxidation-reduction processes was
      evaluated. Microcosms were constructed using indigenous bacteria and activated
      sludge as the inocula and cane molasses and a slow polycolloid-releasing
      substrate (SPRS) as the primary substrates. Complete DCA removal was obtained
      within 30 days under aerobic and reductive dechlorinating conditions. In
      anaerobic microcosms with sludge and substrate addition, chloroethane, vinyl
      chloride, and ethene were produced. The microbial communities and DCA-degrading
      bacteria in microcosms were characterized by 16S rRNA-based denatured-gradient
      gel electrophoresis profiling and nucleotide sequence analyses. Real-time
      polymerase chain reaction was applied to evaluate the variations in
      Dehalococcoides spp. and Desulfitobacterium spp. Increase in Desulfitobacterium
      spp. indicates that the growth of Desulfitobacterium might be induced by DCA.
      Results indicate that DCA could be used as the primary substrate under aerobic
      conditions. The increased ethene concentrations imply that dihaloelimination was
      the dominate mechanism for DCA biodegradation. 

PMID- 25863887
TI  - [Cerebrospinal fluid rhinorrhea from a transclival meningocele: A case report and
      literature review].
AB  - The most common site of CSF leakage is the floor of the anterior cranial fossa,
      and less commonly in the sphenoid sinus. Only 3-4% of CSF fistulas are
      spontaneous. The fourth case is presented of a CSF rhinorrhea due to a
      transclival meningocele, an extremely rare location for these lesions, and the
      surgical approach. The patient is a 39-year-old male with no history of trauma,
      and a recent history of watery rhinorrhe and meningitis. CT scan and MRI showed
      clival bone defect and trans-sphenoidal transclival meningocele. The defect was
      repaired by transclival trans-sphenoidal endoscopic endonasal approach with good
      results. Despite the rarity of transclival meningocele, it is recommended to
      consider it in the differential diagnosis of spontaneous nasal fistulas. The
      endoscopic endonasal approach is a direct technique that provides satisfactory
      results in the resolution of CSF rhinorrhea. 

PMID- 25863888
TI  - Transcriptional profiling by DDRT-PCR analysis reveals gene expression during
      seed development in Carya cathayensis Sarg.
AB  - Hickory (Carya cathayensis Sarg.) seed has one of the highest oil content and is
      rich in polyunsaturated fatty acids (PUFAs), which kernel is helpful to human
      health, particularly to human brain function. A better elucidation of lipid
      accumulation mechanism would help to improve hickory production and seed quality.
      DDRT-PCR analysis was used to examine gene expression in hickory at thirteen time
      points during seed development process. A total of 67 unique genes involved in
      seed development were obtained, and those expression patterns were further
      confirmed by semi-quantitative RT-PCR and real time RT-PCR analysis. Of them, the
      genes with known functions were involved in signal transduction, amino acid
      metabolism, nuclear metabolism, fatty acid metabolism, protein metabolism, carbon
      metabolism, secondary metabolism, oxidation of fatty acids and stress response,
      suggesting that hickory underwent a complex metabolism process in seed
      development. Furthermore, 6 genes related to fatty acid synthesis were explored,
      and their functions in seed development process were further discussed. The data
      obtained here would provide the first clues for guiding further functional
      studies of fatty acid synthesis in hickory. 

PMID- 25863889
TI  - The tolerance of grain amaranth (Amaranthus cruentus L.) to defoliation during
      vegetative growth is compromised during flowering.
AB  - The biochemical processes underlying variations of tolerance are often
      accompanied by source-sink transitions affecting carbon (C) metabolism. We
      investigated the tolerance of Amaranthus cruentus L. to total mechanical
      defoliation through development and in different growing seasons. Defoliated A.
      cruentus recovered ~80% of their above-ground biomass and ~100% of grain yield
      compared to intact plants if defoliation occurred early during ontogeny, but
      could not compensate when defoliation occurred during flowering. Tolerance index
      was higher in the summer season (-0.3) than in the winter season (-0.7). Overall,
      defoliation tolerance was closely related to phosphoenolpyruvate carboxylase
      (PEPC) activity in leaves and the subsequent accumulation of starch (~500
      MUmol/gDW) and sucrose (~140 MUmol/gDW) in stems and roots. Thus, A. cruentus
      accumulated sufficient C in roots and stem to allow branching and shoot re-growth
      after defoliation, but it only possessed sufficient C reserves to maintain <19%
      seed yield in the absence of new vegetative tissue. Seed size was larger during
      the warm season but it was not affected by foliar damage. Seed chemical
      composition was altered by defoliation at flowering. We conclude that A. cruentus
      defoliation tolerance depends on both, the re-allocation of starch from stem and
      roots, and the activation of dormant meristems before flowering to generate new
      photosynthetic capacity to sustain seed filling.

PMID- 25863890
TI  - What is the Fate of Total Hip Arthroplasty (THA) Acetabular Component Orientation
      When Evaluated in the Standing Position?
AB  - This retrospective study measured the change of the acetabular component
      orientation between supine and standing radiographs in 113 THA patients and
      identified the associated anatomical parameters that may help direct pre
      operative planning. The mean change of the acetabular component inclination and
      version from supine to standing was 4.6 degrees  and 5.9 degrees  respectively
      (P<0.0001), with 49 (43%) hips showing inclination change >5 degrees  and 69
      (53%) hips showing version change >5 degrees . Twelve (43%) of 28 'malpositioned'
      cups became 'well-positioned' and 26 (31%) of 85 'well-positioned' cups became
      'malpositioned' upon standing. Changes in inclination were associated with leg
      length discrepancy and pelvic obliquity; and changes in version were associated
      with pelvic tilt and pelvic incidence. Standing position and patient factors
      should be considered when defining "optimal" acetabular orientation.

PMID- 25863891
TI  - Portal and centrilobular hepatic fibrosis in Fontan circulation and clinical
      outcomes.
AB  - BACKGROUND: The Fontan operation redirects venous blood flow directly to the
      pulmonary circulation in subjects with single ventricle anatomy. Congestive
      hepatopathy and cirrhosis have been described in subjects with Fontan
      circulation, but the prevalence of and predictors for liver disease remain
      unknown. METHODS: We performed a retrospective study of liver histopathology in
      Fontan subjects who had liver biopsy or autopsy. All specimens were graded using
      a pre-determined protocol. Additional data were collected through chart review.
      Among 68 subjects, specimens were obtained at a median age of 23.2 years (range
      5.0 to 52.7 years). Median time since Fontan was 18.1 years (range 1.2 to 32.7
      years). RESULTS: Centrilobular fibrosis was seen in every specimen, with 41.2%
      showing Grade 4 centrilobular fibrosis. Portal fibrosis was seen in 82.3% of
      specimens, with 14.7% showing cirrhosis. Megamitochondria were seen in 58.8% of
      specimens. Centrilobular fibrosis grade was greater in those with a dominant left
      or right ventricle than in those with a combined right and left systemic
      ventricle (p = 0.008). Portal fibrosis grade correlated with alkaline phosphatase
      (p = 0.04) and mode of biopsy (p = 0.02). Neither centrilobular fibrosis nor
      portal fibrosis grade was predictive of transplant-free survival or overall
      survival. CONCLUSIONS: Individuals with Fontan physiology have a high prevalence
      of hepatic fibrosis. Signs and symptoms of liver disease did not predict
      histopathologic findings. Few risk factors for advanced disease were identified.
      Histopathology findings did not predict transplant-free survival. The role of
      liver biopsy in this population remains uncertain.

PMID- 25863892
TI  - Multiharmonic electron paramagnetic resonance for extended samples with both
      narrow and broad lines.
AB  - Multiharmonic electron paramagnetic resonance spectroscopy was demonstrated for
      two samples with both narrow and broad lines: (i) alpha,gamma-Bisdiphenylene-beta
      phenylallyl (BDPA) with DeltaBpp of 0.85 G plus ultramarine blue with DeltaBpp of
      17 G, and (ii) a nitroxide radical immobilized in sucrose octaacetate. Modulation
      amplitudes up to 17 G at 41 kHz were generated with a rapid scan coil driver and
      Litz wire coils that provide uniform magnetic field sweeps over samples with
      heights of 5mm. Data were acquired with a 2-D experiment in the Xepr software
      through the transient signal path of a Bruker E500T and digitized in quadrature
      with a Bruker SpecJet II. Signals at the modulation frequency and its harmonics
      were calculated by digital phase-sensitive detection. The number of harmonics
      with signal intensity greater than noise increases as the ratio of the modulation
      amplitude to the narrowest peak increases. Spectra reconstructed by the
      multiharmonic method from data obtained with modulation amplitudes up to five
      times the peak-to-peak linewidths of the narrowest features have linewidths that
      are broadened by up to only about 10% relative to linewidths in spectra obtained
      at low modulation amplitudes. The signal-to-noise improves with increasing
      modulation amplitude up to the point where the modulation amplitude is slightly
      larger than the linewidth of the narrowest features. If this high a modulation
      amplitude had been used in conventional methodology the linewidth of the
      narrowest features would have been severely broadened. The multiharmonic
      reconstruction methodology means that the selection of the modulation amplitude
      that can be used without spectral distortion is no longer tightly tied to the
      linewidth of the narrowest line.

PMID- 25863893
TI  - Reliable resonance assignments of selected residues of proteins with known
      structure based on empirical NMR chemical shift prediction.
AB  - A robust NMR resonance assignment method is introduced for proteins whose 3D
      structure has previously been determined by X-ray crystallography. The goal of
      the method is to obtain a subset of correct assignments from a parsimonious set
      of 3D NMR experiments of (15)N, (13)C labeled proteins. Chemical shifts of
      sequential residue pairs are predicted from static protein structures using
      PPM_One, which are then compared with the corresponding experimental shifts.
      Globally optimized weighted matching identifies the assignments that are robust
      with respect to small changes in NMR cross-peak positions. The method, termed
      PASSPORT, is demonstrated for 4 proteins with 100-250 amino acids using 3D NHCA
      and a 3D CBCA(CO)NH experiments as input producing correct assignments with high
      reliability for 22% of the residues. The method, which works best for Gly, Ala,
      Ser, and Thr residues, provides assignments that serve as anchor points for
      additional assignments by both manual and semi-automated methods or they can be
      directly used for further studies, e.g. on ligand binding, protein dynamics, or
      post-translational modification, such as phosphorylation. 

PMID- 25863894
TI  - Bottom-up study of the MRI positive contrast created by the Off-Resonance
      Saturation sequence.
AB  - Superparamagnetic iron oxide nanoparticles (SPM particles) are used in MRI to
      highlight regions such as tumors through negative contrast. Unfortunately,
      sources as air bubbles or tissues interfaces also lead to negative contrast,
      which complicates the image interpretation. New MRI sequences creating positive
      contrast in the particle surrounding, such as the Off-Resonance Saturation
      sequence (ORS), have thus been developed. However, a theoretical study of the ORS
      sequence is still lacking, which hampers the optimization of this sequence. For
      this reason, this work provides a self-consistent analytical expression able to
      predict the dependence of the contrast on the sequence parameters and the SPM
      particles properties. This expression was validated by numerical simulations and
      experiments on agarose gel phantoms on a 11.7 T scanner system. It provides a
      fundamental understanding of the mechanisms leading to positive contrast, which
      could allow the improvement of the sequence for future in vivo applications. The
      influence of the SPM particle relaxivities, the SPM particle concentration, the
      echo time and the saturation pulse parameters on the contrast were investigated.
      The best contrast was achieved with SPM particles possessing the smallest
      transverse relaxivity, an optimal particle concentration and for low echo times.

PMID- 25863896
TI  - [Ankle-brachial index measurement: Methods of teaching in French medical schools
      and review of literature].
AB  - INTRODUCTION: The ankle-brachial index (ABI) can be measured to diagnose
      peripheral artery disease (PAD) and used as an independent marker of
      cardiovascular risk. What are the teaching methods for ABI in French medical
      schools? What are the data in the literature showing the link between and
      educational interventions and ABI competency? MATERIALS AND METHODS: A
      questionnaire to assess how ABI is taught in the second and third cycles of
      French medical schools was sent to vascular medicine chairs of each faculty. A
      systematic review of the literature in PubMed was performed including articles
      that studied the effect of an educational intervention on this competency.
      RESULTS: Sixty-five percent of vascular medicine chairs (teachers) responded. ABI
      was taught in the second cycle in all medical schools. In 75% of schools, ABI was
      taught as part of lectures on PAD. Practical training was implemented in the
      second cycle in 20% of medical schools and in the third cycle in 60%. Teachers
      are statistically less satisfied with their way of teaching in the second cycle
      compared with the third cycle. Four articles have studied the effect of an
      educational intervention. Practical training improves student performance.
      CONCLUSION: Most of vascular medicine teachers used lectures to teach ABI. This
      type of teaching does not favor the development of this medical competency. The
      best way of teaching this competency should be addressed. Homogenization in the
      way ABI is taught would be necessary at national and international levels.

PMID- 25863895
TI  - Real-time 2D spatially selective MRI experiments: Comparative analysis of optimal
      control design methods.
AB  - There is an increasing need for development of advanced radio-frequency (RF)
      pulse techniques in modern magnetic resonance imaging (MRI) systems driven by
      recent advancements in ultra-high magnetic field systems, new parallel
      transmit/receive coil designs, and accessible powerful computational facilities.
      2D spatially selective RF pulses are an example of advanced pulses that have many
      applications of clinical relevance, e.g., reduced field of view imaging, and MR
      spectroscopy. The 2D spatially selective RF pulses are mostly generated and
      optimised with numerical methods that can handle vast controls and multiple
      constraints. With this study we aim at demonstrating that numerical, optimal
      control (OC) algorithms are efficient for the design of 2D spatially selective
      MRI experiments, when robustness towards e.g. field inhomogeneity is in focus. We
      have chosen three popular OC algorithms; two which are gradient-based, concurrent
      methods using first- and second-order derivatives, respectively; and a third that
      belongs to the sequential, monotonically convergent family. We used two
      experimental models: a water phantom, and an in vivo human head. Taking into
      consideration the challenging experimental setup, our analysis suggests the use
      of the sequential, monotonic approach and the second-order gradient-based
      approach as computational speed, experimental robustness, and image quality is
      key. All algorithms used in this work were implemented in the MATLAB environment
      and are freely available to the MRI community. 

PMID- 25863897
TI  - Standardisation of egg-viability assays for Fasciola hepatica and Calicophoron
      daubneyi: A tool for evaluating new technologies of parasite control.
AB  - Fasciola hepatica and Calicophoron daubneyi, liver and rumen flukes respectively,
      infect ruminants throughout Europe. There is considerable interest in the
      development of vaccines and in testing new potential anthelmintic agents against
      these species. One potential target of new control measures is the parasite egg,
      as interference at this stage of the life cycle could aid in blocking the
      transmission of infection, and some experimental vaccines have been shown to
      affect egg viability. In this study, we describe the standardisation of protocols
      to evaluate the viability of eggs of these two parasites. Eggs were recovered
      from adult parasites collected in a commercial abattoir, from naturally infected
      cattle. A protocol for in vitro development of F. hepatica eggs was optimised
      based on previously published methods, with variations in duration and
      temperature of incubation. A new protocol for measurement of rumen fluke egg
      development in vitro was designed, based on testing different temperatures and
      periods of incubation, with or without light exposure. The protocols described
      here may be used in the future for comparing experimental groups when new
      technologies for parasite control are tested. In addition, the methods described
      for C. daubneyi present new information on the biology of this parasite. 

PMID- 25863898
TI  - Enzymatic production of biodiesel from Nannochloropsis gaditana lipids: Influence
      of operational variables and polar lipid content.
AB  - Fatty acid methyl esters (FAMEs, biodiesel) were produced from Nannochloropsis
      gaditana wet biomass (12% saponifiable lipids, SLs) by extraction of SLs and
      lipase catalyzed transesterification. Lipids were extracted by ethanol (96%)
      hexane, and 31% pure SLs were obtained with 85% yield. When the lipids were
      degummed, SL purity increased to 95%. Novozym 435 was selected from four lipases
      tested. Both the lipidic composition and the use of t-butanol instead of hexane
      increased the reaction velocity and the conversion, since both decreased due to
      the adsorption of polar lipids on the lipase immobilization support. The best
      FAME yield (94.7%) was attained at a reaction time of 48h and using 10mL of t
      butanol/g SL, 0.225gN435/g SL, 11:1 methanol/SL molar ratio and adding the
      methanol in three steps. In these conditions the FAME conversion decreased by
      9.8% after three reaction cycles catalyzed by the same lipase batch. 

PMID- 25863899
TI  - The impact of glycerol organosolv pretreatment on the chemistry and enzymatic
      hydrolyzability of wheat straw.
AB  - Given that the glycerol organosolv pretreatment (GOP) can effectively improve the
      hydrolyzability of various lignocellulosic substrates, physicochemical changes of
      the substrate before and after the pretreatment was characterized to elucidate
      what is responsible for it. The effect of GOP on the main components and
      hydrolyzability of wheat straw was revisited. Results demonstrate that the GOP
      should be a promising candidate for the current pretreatment. Then the
      composition and structure of substrates was measured at multi-dimensional scales
      by using various analytic equipment such as TGA, SEM, AFM, CLSM, FT-IR, XRD and
      solid-state CP/MAS (13)C NMR. This paper reports some new insights on the
      mechanism behind that, which can be beneficial for further development,
      optimization, and scale-up of the GOP process. 

PMID- 25863900
TI  - Reducing beta-glucosidase supplementation during cellulase recovery using
      engineered strain for successive lignocellulose bioconversion.
AB  - Enzyme recycling by re-adsorption is one of the primary methods for reducing
      enzyme usage in lignocellulose conversion. This work proposes the combination of
      an engineered yeast strain that expresses beta-glucosidase with enzyme recycling
      to reduce the amount of supplemented beta-glucosidase in enzyme recycling
      experiments. Using the engineered strain, a slight increase in ethanol
      concentration was obtained after a 96-h fermentation of pretreated corncobs.
      Ethanol concentrations increased by 34.7% and 62.7% in the following two recycle
      rounds using the engineered strain compared with those using its parental strain
      without beta-glucosidase addition. Furthermore, with the addition of beta
      glucosidase at 30CBU/g cellulose, the ethanol concentration after two recycle
      rounds exceeded 90% of that observed in the first SSF round with the engineered
      strain at a high initial cellulase loading of 45FPU/g cellulose. 

PMID- 25863901
TI  - Ultrasound assisted biodesulfurization of liquid fuel using free and immobilized
      cells of Rhodococcus rhodochrous MTCC 3552: A mechanistic investigation.
AB  - This paper attempts to gain mechanistic insight into enhancement effect of
      sonication on biodesulfurization. The approach has been to fit Haldane kinetics
      model to dibenzothiophene (DBT) metabolism and analyze trends in model parameters
      concurrently with simulations of cavitation bubble dynamics. Mechanistic synergy
      between sonication and biodesulfurization is revealed to be of both physical and
      chemical nature. Generation of micro-turbulence in medium by sonication leads to
      fine emulsification and enhancement of DBT transport across organic/aqueous
      interphase. Microturbulence also enhances transport of substrate and product
      across cell wall that increases reaction velocity (Vmax). Michaelis constant (Km)
      and inhibition constant (KI), being intrinsic parameters, remain unaffected by
      sonication. Radicals produced by transient cavitation oxidize DBT to DBT
      sulfoxide and DBT-sulfone (intermediates of metabolism), which contributes
      enhancement of biodesulfurization. However, high shear generated by ultrasound
      and cavitation has adverse effect on action of surfactant beta-cyclodextrin for
      enhancement of interphase transport of DBT. 

PMID- 25863902
TI  - Pyrochars from bioenergy residue as novel bio-adsorbents for lignocellulosic
      hydrolysate detoxification.
AB  - The robust supramolecular structure of biomass often requires severe
      pretreatments conditions to produce soluble sugars. Nonetheless, these processes
      generate some inhibitory compounds (i.e. furans compounds and aliphatic acids)
      deriving mainly from sugars degradation. To avoid the inhibition of the
      biological process and to obtain satisfactory sugars conversion level into
      biofuels, a detoxification step is required. This study investigates the use of
      two pyrochars derived from solid anaerobic digestates for the detoxification of
      lignocellulosic hydrolysates. At a pyrochar concentration of 40gL(-1), more than
      94% of 5-HMF and 99% of furfural were removed in the synthetic medium after 24h
      of contact time, whereas sugars concentration remained unchanged. Furfural was
      adsorbed faster than 5-HMF by both pyrochars and totally removed after 3h of
      contact. Finally, the two pyrochars were found efficient in the detoxification of
      corn stalks and Douglas fir wood chips hydrolysates without affecting the soluble
      sugars concentrations. 

PMID- 25863903
TI  - Basal ganglia contribution to rule expectancy and temporal predictability in
      speech.
AB  - The current work set out to answer three questions: (1) Are reported syntactic
      deficits in patients with structural damage to the basal ganglia (BG) in the
      cortico-striato-thalamo-cortical systems (CSTCS) the result of a syntax specific
      computational deficit or are they potentially a consequence of a generalized
      timing deficit? (2) Do BG patients suffer from a simple beat perception deficit
      in speech comparable to the one reported in music? (3) Can regular speech meter
      (i.e., a pattern of beats induced by the regular alteration of stressed and
      unstressed syllable accents) ameliorate the computation of syntactically marked
      information by making speech events temporally predictable and salient? The
      latter 'remediation' hypothesis would predict that when speech events (i.e.,
      those that are syntactically marked) are metrically aligned to the syllabic
      accent structure, the computation of syntactic information is facilitated or in
      the case of patients ameliorated. During continuous EEG measurement nineteen
      patients with focal BG lesions and matched healthy controls listened to
      metrically regular and syntactically well-formed sentences and metrically well
      formed sentences that either violated syntactic expectancy, metrical expectancy,
      or both. While healthy controls showed an expected P600 response in the event
      related brain potential (ERP) to all expectancy violations, BG patients showed
      overall comparable P600 responses to all, but the metrical expectancy violation.
      These results confirm that (1) BG patients suffer from a simple beat perception
      deficit in speech and (2) regular speech meter ameliorates the computation of
      syntactically marked information in the speech signal. We propose that a domain
      general sensorimotor cerebello-thalamo-cortical system (CTCS), involved in event
      based temporal processing, engages in the remediation of dysfunctional cortico
      striato-thalamo-cortical timing that affects the timely computation of linguistic
      (i.e., syntax) information in the speech signal. 

PMID- 25863905
TI  - A simple model for predicting lung cancer occurrence in a lung cancer screening
      program: The Pittsburgh Predictor.
AB  - BACKGROUND: A user-friendly method for assessing lung cancer risk may help
      standardize selection of current and former smokers for screening. We evaluated a
      simple 4-factor model, the Pittsburgh Predictor, against two well-known, but more
      complicated models for predicting lung cancer risk. METHODS: Trained against
      outcomes observed in the National Lung Screening Trial (NLST), the Pittsburgh
      Predictor used four risk factors, duration of smoking, smoking status, smoking
      intensity, and age, to predict 6-year lung cancer incidence. After calibrating
      the Bach and PLCOM2012 models to outcomes observed in the low-dose computed
      tomography arm of the NLST, we compared model calibration, discrimination, and
      clinical usefulness (net benefit) in the NLST and Pittsburgh Lung Screening Study
      (PLuSS) populations. RESULTS: The Pittsburgh Predictor, Bach, and PLCOM2012
      represented risk equally well, except for the tendency of PLCOM2012 to
      overestimate risk in subjects at highest risk. Relative to the Pittsburgh
      Predictor, Bach and PLCOM2012 increased the area under the receiver operator
      characteristic curve by 0.007-0.009 and 0.012-0.021 units, respectively,
      depending on study population. Across a clinically relevant span of 6-year lung
      cancer risk thresholds (0.01-0.05), Bach and PLCOM2012 increased net benefit by
      less than 0.1% in NLST and 0.3% in PLuSS. CONCLUSION: In exchange for a small
      reduction in prediction accuracy, a simpler lung cancer risk prediction model may
      facilitate standardized procedures for advising and selecting patients with
      respect to lung cancer screening.

PMID- 25863904
TI  - Demographics, management and survival of patients with malignant pleural
      mesothelioma in the National Lung Cancer Audit in England and Wales.
AB  - INTRODUCTION AND METHODS: Malignant pleural mesothelioma (MPM) is an uncommon
      cancer with poor survival. We have used data collected for the UK National Lung
      Cancer Audit to assess current practice and to highlight regional variation in
      the management of mesothelioma patients, as well as to describe survival patterns
      in subgroups. RESULTS: Our data on 8740 cases seen in hospitals in England and
      Wales is the largest cohort of MPM in the literature and represents approximately
      80% of the total incident cases. 83% are male and median age is 73 years.
      Performance status is recorded in 81% and of these approximately 70% are PS 0-2.
      Stage is poorly recorded and unreliable in this dataset. The patient pathway is
      similar to lung cancer with approximately one-fifth having a non-elective
      referral to secondary care. A histo-cytological diagnosis is made in 87% and
      varies across organisations. Only 67% have anti-cancer treatment, and this also
      varies across organisations, but there has been an annual increase in the
      proportion receiving chemotherapy. Overall median survival was 9.5 months, with a
      1YS of 41.4% and 3YS of 12.0%, but was strongly linked to performance status and
      histological subtype. Median survival also varied by cancer network from 209 days
      to 349 days, but appeared to increase from of 9.2 months in 2008 to 10.5 months
      in 2012. CONCLUSION: Our data provide a large scale, detailed assessment of MPM
      epidemiology, treatment choices and outcomes. Incidence is increasing in line
      with predictions and uptake of treatments has generally mirrored publication of
      key MPM treatment trials, in particular increasing use of chemotherapy but low
      uptake of radical surgery. However, there is significant variation in care
      patterns and outcomes that may reflect limited expertise in area with low
      incidence. Initiatives to improve outcomes should include improved recording of
      clinical stage.

PMID- 25863906
TI  - Childhood-compared to adolescent-onset bipolar disorder has more statistically
      significant clinical correlates.
AB  - BACKGROUND: The strengths and limitations of considering childhood-and adolescent
      onset bipolar disorder (BD) separately versus together remain to be established.
      We assessed this issue. METHODS: BD patients referred to the Stanford Bipolar
      Disorder Clinic during 2000-2011 were assessed with the Systematic Treatment
      Enhancement Program for BD Affective Disorders Evaluation. Patients with
      childhood- and adolescent-onset were compared to those with adult-onset for 7
      unfavorable bipolar illness characteristics with replicated associations with
      early-onset patients. RESULTS: Among 502 BD outpatients, those with childhood-
      (<13 years, N=110) and adolescent- (13-18 years, N=218) onset had significantly
      higher rates for 4/7 unfavorable illness characteristics, including lifetime
      comorbid anxiety disorder, at least ten lifetime mood episodes, lifetime alcohol
      use disorder, and prior suicide attempt, than those with adult-onset (>18 years,
      N=174). Childhood- but not adolescent-onset BD patients also had significantly
      higher rates of first-degree relative with mood disorder, lifetime substance use
      disorder, and rapid cycling in the prior year. Patients with pooled
      childhood/adolescent - compared to adult-onset had significantly higher rates for
      5/7 of these unfavorable illness characteristics, while patients with childhood-
      compared to adolescent-onset had significantly higher rates for 4/7 of these
      unfavorable illness characteristics. LIMITATIONS: Caucasian, insured, suburban,
      low substance abuse, American specialty clinic-referred sample limits
      generalizability. Onset age is based on retrospective recall. CONCLUSIONS:
      Childhood- compared to adolescent-onset BD was more robustly related to
      unfavorable bipolar illness characteristics, so pooling these groups attenuated
      such relationships. Further study is warranted to determine the extent to which
      adolescent-onset BD represents an intermediate phenotype between childhood- and
      adult-onset BD.

PMID- 25863907
TI  - DEPERROR: Risks of systematic errors in drug and non-drug randomized clinical
      trials assessing intervention effects in patients with unipolar depression.
AB  - BACKGROUND: Systematic errors in randomized clinical trials (RCTs) overestimate
      treatment effects. We systematically assessed the risks of bias in RCTs assessing
      the effects of drug and non-drug interventions for patients with unipolar
      depression. METHODS: We searched bibliographic databases for drug and non-drug
      RCTs including patients with depression. We assessed the following risk of bias
      domains: sequence generation, allocation concealment, baseline imbalance,
      blinding, intention-to-treat analysis, selective outcome reporting, and funding.
      Risks of bias were compared for drug and non-drug trials and according to year of
      publication (before 1990; from 1990 to 1999; and 2000 to 2010). RESULTS:
      Comparing drug trials (N=775) to non-drug trials (N=73), the proportion of drug
      trials with low risk of bias seemed superior regarding blinding of participants
      (p<0.001), blinding of health-care providers (p<0.001), and blinded outcome
      assessment (p<0.001). Non-drug trials were superior regarding sequence generation
      (p<0.001), allocation concealment (p=0.002), intention-to-treat analysis
      (p<0.001), and baseline imbalance (p=0.006). Adequate blinding of data managers
      (p=0.45), blinding of statisticians (p=0.69), and selective outcome reporting
      (p=0.55) did not differ. 41.5% of drug trials were funded by for-profit
      organizations compared to 12.3% of non-drug trials (p<0.001). In drug trials, the
      risk of bias decreased significantly over time. This did not reach statistical
      significance in non-drug trials. LIMITATIONS: This study only included trials
      published before 2010. CONCLUSIONS: Included trials were associated with high
      risks of bias which may distort effect estimates. The risks of bias decreased
      with time for drug trials.

PMID- 25863908
TI  - Intrinsic religiosity, resilience, quality of life, and suicide risk in depressed
      inpatients.
AB  - BACKGROUND: Religiosity is inversely related to depression and is directly
      associated with positive psychological outcomes. Nonetheless, there is no
      consensus on whether or how religiosity could impact and protect against
      depression. The present study evaluated the association between intrinsic
      religiosity and resilient psychological characteristics in depressed inpatients.
      METHODS: A sample of 143 depressed patients was prospectively evaluated in an
      inpatient psychiatric treatment in South Brazil. High Intrinsic Religiosity (HIR)
      and Low Intrinsic Religiosity (LIR) patients were compared across socio
      demographic information, clinical measures, religiosity, resilience and quality
      of life. A linear regression model was used to evaluate the association between
      intrinsic religiosity and resilience, and the Cohen d test was utilized to assess
      effect sizes. RESULTS: At admission, HIR patients showed higher HAM-D (p=0.05),
      BPRS (p=0.02), GAF (p=0.02), and CGI (p=0.03) scores, lower educational levels
      (p=0.04), higher social support (p=0.05), and fewer previous suicide attempts
      (p=0.05). At discharge, HIR patients showed higher quality of life (p=0.001) and
      higher resilience (p=0.000), with a large effect size difference between groups
      (1.02). Based on a linear regression model (adjusted r=0.19, p=0.000), intrinsic
      religiosity was associated with resilience, controlling for covariates.
      CONCLUSION: In a sample of depressed inpatients, intrinsic religiosity was found
      to be associated with resilience, quality of life, and fewer previous suicide
      attempts. These findings support the relevance of religiosity assessments in
      mental health practice and support the hypothesis that resilient psychological
      characteristics may mediate the positive effects of intrinsic religiosity in
      depression.

PMID- 25863909
TI  - The association of relationship quality and social networks with depression,
      anxiety, and suicidal ideation among older married adults: Findings from a cross
      sectional analysis of the Irish Longitudinal Study on Ageing (TILDA).
AB  - BACKGROUND: Important associations have been found between social relationships
      and various mental health outcomes. However, limited data exists for these
      associations among older adults especially in terms of relationship quality in
      partnerships. This study aimed to examine the associations of positive and
      negative partner interactions and social networks with depression, anxiety and
      suicidal ideation. METHODS: Nationally-representative, cross-sectional data of
      the Irish Longitudinal Study on Ageing (TILDA) was analyzed. The analytical
      sample consisted of 4988 community dwelling adults aged >50 years in
      spouse/partner relationships. Information on sociodemographics and social
      relationships were assessed using standard questions. Validated scales for
      depression and anxiety, and a single-item question for suicidal ideation were
      used to assess mental health outcomes. Multivariable logistic regression was used
      to assess the association between social relationships and depression, anxiety,
      and suicidal ideation. RESULTS: After adjusting for confounders, negative partner
      interactions were significantly associated with increased likelihood of
      depression, anxiety, and suicidal ideation, while positive partner interactions
      were significantly and inversely related to anxiety and suicidal ideation. Higher
      levels of social integration were significantly associated with lower odds for
      depression. LIMITATIONS: Given the cross-sectional nature of the research, no
      firm conclusions can be made in terms of directions of causality. CONCLUSION: By
      assessing the available social network of older adults, as well as the areas in
      their social relationships that need to be addressed, it may be possible for
      practitioners and policy makers to maximize the benefits of network integration
      and minimize the potentially harmful aspects of social relationships, thereby
      improving overall mental health and emotional well-being.

PMID- 25863910
TI  - Does a history of substance abuse and illness chronicity predict increased
      impulsivity in bipolar disorder?
AB  - BACKGROUND: Impulsivity is a common feature shared by bipolar disorder (BD) and
      substance use disorder (SUD). SUD and recurrent mood episodes are considered to
      be risk factors for poor outcome in BD. However, the association between
      impulsivity, illness chronicity and SUD in BD remains unexplored. METHODS: 103 BD
      patients with and without a lifetime history of SUD (36.82+/-11.34 years, 40
      males) were recruited. Participants completed the SCID interview and were
      administered measures of impulsivity including the Barratt Impulsivity Scale
      (BIS) and selected tests of the Cambridge Neuropsychological Test Automated
      Battery (CANTAB). Hierarchical regression analyses explored the relationship
      between illness chronicity, SUD, and impulsivity. RESULTS: Variance in the BIS,
      number of false alarms on the Rapid Visual Processing task and other impulsivity
      indicators of the Cambridge Gambling Task (CGT) was not explained by the chosen
      variables. Only an increased number of commission errors in the negative
      condition of the Affective Go/No Go task was significantly associated with
      illness chronicity. Furthermore there was a trend suggesting a relationship
      between a lifetime history of SUD and increased propensity to risk-taking during
      the CGT. LIMITATIONS: Potential limitations include medication and patients'
      remission status from SUD. CONCLUSIONS: Contrary to our expectations impulsivity
      was generally not predicted by indicators of illness chronicity or SUD. While
      impulsivity could still be a marker of BD that is present before the onset of the
      disorder, the link between the number of mood episodes and specific indicators of
      impulsivity may be related to mechanisms of neuroprogression.

PMID- 25863911
TI  - Factors influencing insulin resistance in relation to atherogenicity in mood
      disorders, the metabolic syndrome and tobacco use disorder.
AB  - OBJECTIVE: This study examines the effects of malondialdehyde (MDA) and uric acid
      on insulin resistance and atherogenicity in subjects with and without mood
      disorders, the metabolic syndrome (MetS) and tobacco use disorder (TUD). METHODS:
      We included 314 subjects with depression and bipolar depression, with and without
      the MetS and TUD and computed insulin resistance using the updated homeostasis
      model assessment (HOMA2IR) and atherogenicity using the atherogenic index of
      plasma (AIP), that is log10 (triglycerides/high density lipoprotein (HDL)
      cholesterol. RESULTS: HOMA2IR is correlated with body mass index (BMI) and uric
      acid levels, but not with mood disorders and TUD, while the AIP is positively
      associated with BMI, mood disorders, TUD, uric acid, MDA and male sex. Uric acid
      is positively associated with insulin and triglycerides and negatively with HDL
      cholesterol. MDA is positively associated with triglyceride levels. Comorbid mood
      disorders and TUD further increase AIP but not insulin resistance. Glucose is
      positively associated with increasing age, male gender and BMI. DISCUSSION: The
      results show that mood disorders, TUD and BMI together with elevated levels of
      uric acid and MDA independently contribute to increased atherogenic potential,
      while BMI and uric acid are risk factors for insulin resistance. The findings
      show that mood disorders and TUD are closely related to an increased atherogenic
      potential but not to insulin resistance or the MetS. Increased uric acid is a
      highly significant risk factor for insulin resistance and increased atherogenic
      potential. MDA, a marker of lipid peroxidation, further contributes to different
      aspects of the atherogenic potential. Mood disorders and TUD increase
      triglyceride levels, lower HDL cholesterol and are strongly associated with the
      atherogenic, but not insulin resistance, component of the MetS.

PMID- 25863912
TI  - Chronology of illness in dual diagnosis heroin addicts: The role of mood
      disorders.
AB  - BACKGROUND: Recent celebrity deaths have been widely reported in the media and
      turned the public attention to the coexistence of mood, psychiatric and substance
      abuse disorders. These tragic and untimely deaths motivated us to examine the
      scientific and clinical data, including our own work in this area. The self
      medication hypothesis states that individuals with psychiatric illness tend to
      use heroin to alleviate their symptoms. This study examined the correlations
      between heroin use, mood and psychiatric disorders, and their chronology in the
      context of dual diagnosis. METHODS: Out of 506 dual diagnosed heroin addicts, 362
      patients were implicated in heroin abuse with an onset of at least one year prior
      to the associated mental disorder (HER-PR), and 144 patients were diagnosed of
      mental illness at least one year prior to the associated onset of heroin use
      disorder (MI-PR). The retrospective cross-sectional analysis of the two groups
      compared their demographic, clinical and diagnostic characteristics at univariate
      and multivariate levels. RESULTS: Dual diagnosis heroin addicts whose heroin
      dependences existed one year prior to their diagnoses (HER-PR) reported more
      frequent somatic comorbidity (p<=0.001), less major problems at work (p=0.003),
      more legal problems (p=0.004) and more failed treatment for their heroin
      dependence (p<0.001) in the past. More than 2/3 reached the third stage of heroin
      addiction (p=<0.001). Their length of dependence was longer (p=0.004). HER-PR
      patients were diagnosed more frequently as affected by mood disorders and less
      frequently as affected by psychosis (p=0.004). At the multivariate level, HER-PR
      patients were characterized by having reached stage 3 of heroin dependence
      (OR=2.45), diagnosis of mood disorder (OR=2.25), unsuccessful treatment (OR=2.07)
      and low education (OR=1.79). LIMITATIONS: The main limitation is its
      retrospective nature. Nonetheless, it does shed light on what needs to be done
      from a clinical and public health perspective and especially prevention.
      CONCLUSIONS: The data emerging from this study, does not allow us to determine a
      causal relation between heroin use and mental illness onset. However, this data,
      even if requiring longitudinal studies, suggest that self-medication theory, in
      these patients, can be applied only for chronic psychoses, but should not be
      applied to patients with mood disorders using heroin.

PMID- 25863913
TI  - Cognitive deterioration among bipolar disorder patients infected by Toxoplasma
      gondii is correlated to interleukin 6 levels.
AB  - BACKGROUND: Cognitive deficits are present in a large majority of Bipolar
      Disorder (BD) patients and known to be a marker of bad prognosis. Because, these
      deficits encompass several domains and no specific medical treatment seems to be
      effective, it is important to better understand the mechanisms underlying
      cognitive deterioration. As Toxoplasma gondii is known to induce the synthesis of
      pro-inflammatory cytokines such as IL-6, we will explore here the possible role
      of T. gondii in the cognitive decline observed in BD. METHODS: 42 euthymic BD
      patients and 36 controls were assessed for episodic verbal memory using the CVLT
      and for working memory and verbal ability using the WAIS III. Patients and
      controls were also screened for seropositivity to T. gondii and evaluated for the
      levels of IL-6 transcripts. RESULTS: The seropositivity for T. gondii was
      significantly higher in BD patients as compared to controls (p=0.005). The
      cognitive deterioration index (DI) was higher in BD patients (p=5.10(-6)) and
      correlated to high IL-6 mRNA expression only among those infected by T. gondii
      (rho=0.43, p=0.01). Among deteriorated patients (defined by scores above 0.10
      according to Weschler's definition), the IL-6 mRNA expression was twice greater
      (p=0.01). LIMITATIONS: Our results are to be interpreted with caution because of
      our small sample size and the cross-sectional design. CONCLUSIONS: A long-term
      exposure to inflammation, measured here with IL-6 mRNA expression in T. gondii
      infected BD may alter cognitive functioning. IL-6 could thus be a useful
      predictive marker of cognitive deterioration in BD and may help to design
      personalized treatment.

PMID- 25863915
TI  - HIRAID: An evidence-informed emergency nursing assessment framework.
AB  - INTRODUCTION: Emergency nurses must be highly skilled at performing accurate and
      comprehensive patient assessments. In 2008, the inaugural emergency nursing
      assessment framework (ENAF) was devised at Sydney Nursing School, to provide
      emergency nurses with a systematic approach to initial patient assessment. In
      2014 the assessment framework was re-developed to reflect the most recent
      evidence. AIM: To describe the process and evidence used to re-develop ENAF, to
      provide ED nurses with an evidence-informed approach to the comprehensive
      assessment of patients presenting to ED after triage, so that it may be
      implemented and tested in the clinical (simulated) setting. METHODS: A thorough
      literature review was conducted to inform the re-development of ENAF. Literature
      review findings were reviewed and ENAF was re-developed by a panel of expert
      emergency nursing clinicians using the Delphi Technique. RESULTS: Modifications
      to ENAF were undertaken and a new, more comprehensive assessment framework was
      developed titled 'HIRAID'. HIRAID is informed by current evidence, comprising of
      seven assessment components: History; Identify Red flags; Assessment;
      Interventions; Diagnostics; reassessment and communication. CONCLUSION: HIRAID
      provides an evidence-informed systematic approach to initial patient assessment
      performed by emergency nurses after triage. Evaluation is now needed to determine
      its impact on clinician performance and patient safety.

PMID- 25863914
TI  - A case-control study of the difficulties in daily functioning experienced by
      children with depressive disorder.
AB  - OBJECTIVE: The parent-assessed children-with-difficulties questionnaire
      (Questionnaire-Children with Difficulties; QCD) is designed to evaluate a child's
      difficulties in functioning during specific periods of the day. This study aimed
      to use the QCD to evaluate the difficulties in daily functioning experienced by
      children with depressive disorders. METHODS: A case-control design was used. The
      cases comprised 90 junior high school students with depressive disorder, whereas
      a community sample of 363 junior high school students was enrolled as controls.
      Behaviors were assessed using the QCD, Depression Self-Rating Scale (DSRS), Tokyo
      Autistic Behavior Scale (TABS), attention deficit hyperactivity disorder-rating
      scale (ADHD-RS), and Oppositional Defiant Behavior Inventory (ODBI). We then
      analyzed the effects of sex and diagnosis on the QCD scores as well as the
      correlation coefficients between the QCD and the other questionnaires. RESULTS:
      We included 90 cases (33 boys, 57 girls) with depressive disorders and 363
      controls (180 boys, 183 girls). The QCD scores for the children with depressive
      disorders were significantly lower compared with those from the community sample
      (P<0.001). The morning, school-time, and night subscores of the QCD were lower
      for the children with both depressive disorders and truancy problems than for
      those with depressive disorders alone (P<0.001). Significant correlations were
      observed between the following: the night QCD subscore and the DSRS scores among
      boys, the morning QCD subscore and ADHD-RS inattention scores for all groups, and
      the evening QCD subscore and the TABS score. CONCLUSIONS: Parents reported that
      children with depressive disorders experienced greater difficulties in completing
      basic daily activities compared with community controls. These difficulties were
      dependent on sex, symptoms, and the time of day. The use of QCD to assess
      children with depressive disorders enables clinicians to clarify the time periods
      at which the children face difficulties.

PMID- 25863916
TI  - Presidential welcome--the American Association of Medical Dosimetrists: 40 years
      in the making.

PMID- 25863917
TI  - Workforce and salary survey trends: opportunities and challenges for the American
      Association of Medical Dosimetrists.
AB  - The American Association of Medical Dosimetrists (AAMD) designed and directed 2
      surveys of the AAMD membership. The first was in 2011 and the second in 2014.
      There were a number of questions common to both surveys, and this article seeks
      to evaluate these common questions to determine trends among the professional
      membership of the AAMD. It is demonstrated that the observed trends are
      consistent with the goals and objectives established by the leadership of the
      AAMD and the Medical Dosimetry Certification Board (MDCB) for the medical
      dosimetry community. In addition, certain challenges and opportunities involving
      the scope of practice for the medical dosimetry profession are discussed. 

PMID- 25863919
TI  - Mobile phones in residential treatment: implications for practice.
AB  - A nonprofit primary care, substance abuse and mental health treatment provider
      that operates nine separate residential treatment facilities in both northern and
      southern California began allowing clients to keep their mobile phones while in
      treatment. From the advent of mobile phone technology and its widespread adoption
      through early 2013, the organization prohibited clients from having phones while
      in treatment. Calls to and from clients needed to be made and received at the
      house phone. After years of enforcing the policy with diminished success as
      phones became cheaper, smaller, and more prevalent, agency leadership decided to
      experiment with allowing the clients to keep their phones while in treatment.
      Elopement data as they relate to the policy are examined along with data from
      staff interviews about its implementation and impact. Results show that
      elopements resulting from being caught with a mobile phone were eliminated and
      some clients were able to be returned to treatment using the devices. All seven
      (100%) of the interviewees were supportive of the new policy and thought it
      should be continued. The impact of the policy on clinical disruptions,
      lost/stolen property liability, and confidentiality issues are discussed. 

PMID- 25863918
TI  - Networking in the nucleus: a spotlight on LEM-domain proteins.
AB  - Proteins resident in the inner nuclear membrane and underlying nuclear lamina
      form a network that regulates nuclear functions. This review highlights a
      prominent family of nuclear lamina proteins that carries the LAP2-emerin-MAN1
      domain (LEM-D). LEM-D proteins share an ability to bind lamins and tether
      repressive chromatin at the nuclear periphery. The importance of this family is
      underscored by findings that loss of individual LEM-D proteins causes
      progressive, tissue-restricted diseases, known as laminopathies. Diverse
      functions of LEM-D proteins are linked to interactions with unique and
      overlapping partners including signal transduction effectors, transcription
      factors and architectural proteins. Recent investigations suggest that LEM-D
      proteins form hubs within the nuclear lamina that integrate external signals
      important for tissue homeostasis and maintenance of progenitor cell populations. 

PMID- 25863920
TI  - [Squamous cell carcinoma following photodynamic therapy].

PMID- 25863921
TI  - [Item 114 - UE 4 Psoriasis].

PMID- 25863922
TI  - [Pyoderma gangrenosum and neutrophilic aortitis preceding the development of
      rheumatoid arthritis].
AB  - BACKGROUND: We report a case of pyoderma gangrenosum (PG) associated with a
      complication comprising ascending aortic dissection (neutrophilic aortitis) in a
      setting of rheumatoid arthritis (RA). PATIENTS AND METHODS: A 79-year-old female
      patient was hospitalized in late 2009 for vegetating PG. Treatment with general
      steroids followed by colchicine and topical steroids resulted in complete healing
      of skin lesions. During hospitalization, the patient presented dissection of the
      ascending part of the aorta, for which emergency surgery proved effective.
      Histological examination of the excised tissue revealed diffuse neutrophilic
      aortitis. Diagnoses of Takayashu's disease and of lupus were ruled out. A chest
      CT scan showed interstitial lung disease with mild lymphocytosis in the
      bronchoalveolar fluid, but with no isolated pathogenic organisms. Relapse of skin
      lesions occurred 3 and 4 years later, associated with the development of RA, and
      worsening of the interstitial lung disease was noted in a scan carried out it in
      2013, following which stabilization was observed in April 2014. There was no
      recurrence of the PG lesions. CONCLUSION: To our knowledge, no other cases
      involving association of neutrophilic aortitis with PG and RA has been published
      to date. The literature describes the emergence of the concept of systemic
      neutrophilic dermatoses, and this notion is reinforced by the presence of a
      cutaneous and aortic site of the neutrophilic disease in a single patient.

PMID- 25863923
TI  - Effects of Context Type on Lipreading and Listening Performance and Implications
      for Sentence Processing.
AB  - PURPOSE: This study compared the use of 2 different types of contextual cues
      (sentence based and situation based) in 2 different modalities (visual only and
      auditory only). METHOD: Twenty young adults were tested with the Illustrated
      Sentence Test (Tye-Murray, Hale, Spehar, Myerson, & Sommers, 2014) and the Speech
      Perception in Noise Test (Bilger, Nuetzel, Rabinowitz, & Rzeczkowski, 1984;
      Kalikow, Stevens, & Elliott, 1977) in the 2 modalities. The Illustrated Sentences
      Test presents sentences with no context and sentences accompanied by picture
      based situational context cues. The Speech Perception in Noise Test presents
      sentences with low sentence-based context and sentences with high sentence-based
      context. RESULTS: Participants benefited from both types of context and received
      more benefit when testing occurred in the visual-only modality than when it
      occurred in the auditory-only modality. Participants' use of sentence-based
      context did not correlate with use of situation-based context. Cue usage did not
      correlate between the 2 modalities. CONCLUSIONS: The ability to use contextual
      cues appears to be dependent on the type of cue and the presentation modality of
      the target word(s). In a theoretical sense, the results suggest that models of
      word recognition and sentence processing should incorporate the influence of
      multiple sources of information and recognize that the 2 types of context have
      different influences on speech perception. In a clinical sense, the results
      suggest that aural rehabilitation programs might provide training to optimize use
      of both kinds of contextual cues.

PMID- 25863924
TI  - Single vial sample preparation of markers of nerve agents by dispersive solid
      phase extraction using magnetic strong anion exchange resins.
AB  - A sample preparation method involving extraction, enrichment and derivatization
      of acidic degradation products of nerve agents was developed using magnetic
      strong anion exchange resins (MSAX). The method was performed in a single vial
      involving magnetic dispersive solid phase extraction (MDSPE). Analytes were
      derivatized with N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) in the
      presence of resins. MSAX were custom synthesized using Fe3O4 nanoparticles as
      core, 4-vinylpyridine-co-divinylbenzene as polymer shell and quaternary
      pyridinium function as anion-exchanger. Hydroxide ions were the counter-anions of
      MSAX to effectively capture the acidic alkyl alkylphosphonic acids (AAPAs) and
      alkylphosphonic acids (APAs). Quantitative measurements of analytes were
      performed in the selected ion monitoring mode of GC-MS. Full scan mode of
      analysis was followed for identifications. Under the optimized conditions
      analytes were recovered in the range of 39.7-98.8% (n=3, relative standard
      deviations (RSD) from 0.3 to 6.5%). Limits of detection (LODs) were in the range
      of 0.1-1.1ngmL(-1); and the linear dynamic range was 5-1000ngmL(-1) with r(2) of
      0.9977-0.9769. Applicability of the method was tested with rain-, tap-, muddy
      water and Organization for Prohibition of Chemical Weapons (OPCW) Proficiency
      Test samples. 

PMID- 25863925
TI  - Determination of volatile organic compounds in water using headspace knotted
      hollow fiber microextraction.
AB  - An efficient and effective headspace microextraction technique named static
      headspace knotted hollow fiber microextraction (HS-K-HFME) has been developed for
      the determination of volatile organic compounds (VOCs) in water samples. The knot
      shaped hollow fiber is filled with 25MUL of the extraction solvent. The excess
      solvent forms a large droplet (13MUL) and is held in the center of the knot. Even
      after 20min of extraction time at high temperature (95 degrees C) without
      cooling, there was still enough volume of extraction solvent for gas
      chromatography-mass spectrometry (GC-MS) analysis, which extends the choice of
      solvents for headspace LPME. Moreover, the knot-shaped fiber has a larger
      extraction contact interface, which increases the rate of mass transfer between
      the headspace and extraction solvent film attached to the fiber, thus improving
      the extraction efficiency. The effects of extraction solvent, temperature,
      stirring rate, salt concentration and extraction time on extraction performance
      were optimized. The calibration curves exhibited coefficients of determination
      (R(2)) ranging from 0.9957 to 0.9999 and the limit of detection (LOD) ranged from
      0.2 to 10MUgL(-1). Relative standard deviations (RSDs) ranged from 4.5% to 11.6%
      for intraday measurements (n=5). Interday (n=15) values were between 2.2% and
      12.9%. The relative recoveries (RRs) ranged from 90.3% to 106.0% for river water
      and 95.9% to 103.6% for wastewater. 

PMID- 25863926
TI  - Development of a novel graphene/polyaniline electrodeposited coating for on-line
      in-tube solid phase microextraction of aldehydes in human exhaled breath
      condensate.
AB  - In this work, we introduced a novel graphene/polyaniline (G/PANI)
      electrodeposited coating for on-line in-tube solid phase microextraction (IT
      SPME) for the first time. The G/PANI coating was prepared on the internal surface
      of stainless steel tube by a facile in-situ electrodeposition method. The
      morphology and formation of the composite coating were confirmed by scanning
      electronic microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR).
      Some important experimental parameters that could affect the extraction and
      separation such as the coating thickness, internal diameter of tube, sampling
      flow rate as well as sample volume were optimized. The extraction performance of
      the IT-SPME coating was evaluated systematically. The coating exhibited enhanced
      mechanical stability, long lifespan, large specific surface area and good
      biocompatibility compared with polyaniline coating. The on-line IT-SPME method
      showed higher enrichment efficiency, faster analysis speed and higher automation
      level than off-line manual mode. Six aldehydes were determined simultaneously
      with low limits of detection of 0.02-0.04nmolL(-1) and good linearity
      (R(2)>=0.9920). The method has been applied successfully for the determination of
      aldehydes in human exhaled breath condensates with good recovery (70-120%) and
      satisfied reproducibility (relative standard deviation: 1.1-11.9%). This on-line
      IT-SPME method provides a promising approach for the determination of trace
      aldehydes with approving sensitivity in human exhaled breath condensates. 

PMID- 25863927
TI  - How parents introduce new words to young children: The influence of development
      and developmental disorders.
AB  - This study documents how parents weave new words into on-going interactions with
      children who are just beginning to speak. Dyads with typically developing
      toddlers and with young children with autism spectrum disorder and Down syndrome
      (n=56, 23, and 29) were observed using a Communication Play Protocol during which
      parents could use novel words to refer to novel objects. Parents readily
      introduced both labels and sound words even when their child did not respond
      expressively or produce the words. Results highlight both how parents act in ways
      that may facilitate their child's appreciation of the relation between a new word
      and its referent and how they subtly adjust their actions to suit their child's
      level of word learning and specific learning challenges. 

PMID- 25863928
TI  - Mitral repair claims victory over replacement at the time of aortic valve
      operation.

PMID- 25863929
TI  - Surgery for acute type A dissection using total arch replacement combined with
      stented elephant trunk implantation: Preservation of autologous brachiocephalic
      vessels.
AB  - OBJECTIVE: Various techniques have been introduced to treat acute type A
      dissection during aortic arch reconstruction. We retrospectively reviewed our
      experience of total arch replacement, with implantation of a stented elephant
      trunk, using preservation of autologous brachiocephalic vessels in patients with
      acute type A dissection. METHODS: Between August 2011 and April 2013, 20 patients
      (16 men, 4 women; mean age, 45 +/- 10 years, range, 24-62 years) with acute type
      A dissection underwent total arch replacement combined with stented elephant
      trunk implantation, using preservation of autologous brachiocephalic vessels
      under hypothermic cardiopulmonary bypass with selective antegrade cerebral
      perfusion. RESULTS: No in-hospital deaths occurred. A transient neurologic
      deficit occurred in 1 patient, who ultimately required tracheotomy. Reoperation
      was indicated in 1 patient for bleeding. All patients survived and were
      discharged. During the mean follow-up period of 26 +/- 7 months, 1 patient
      underwent thoracoabdominal aortic replacement, and 1 patient was lost to follow
      up. The patency of the anastomotic site between the left subclavian artery and
      the left common carotid artery was confirmed on computed tomography scanning.
      CONCLUSIONS: This technique simplified hemostasis and anastomosis, reduced the
      size of the residual aortic wall, and preserved the autologous brachiocephalic
      vessels, yielding satisfactory surgical results. This technique is an alternative
      approach for suitable patients with acute type A dissection. However, outcomes
      are preliminary, and long-term follow up is required.

PMID- 25863930
TI  - Multibranched hybrid device for frozen elephant trunk: What does it change?

PMID- 25863931
TI  - Defining enabling technology for aortic valve replacement.

PMID- 25863932
TI  - Historical perspectives of The American Association for Thoracic Surgery: Richard
      Hardaway Meade, Jr (1897-1993).

PMID- 25863933
TI  - Combining cannula and crossclamp: Not a "Cannulo-Matic," but a versatile
      technique in the cardiac toolbox.

PMID- 25863934
TI  - Predictors of moderate ischemic mitral regurgitation improvement after off-pump
      coronary artery bypass.
AB  - OBJECTIVE: The aim of this study was to explore the predictors of improvement of
      moderate ischemic mitral regurgitation after off-pump coronary artery bypass
      grafting. METHODS: A prospective study was performed among 109 patients (aged
      66.6 +/- 8.6 years, 34.6% were female) with prior myocardial infarction and
      moderate ischemic mitral regurgitation undergoing off-pump coronary artery bypass
      grafting. Preoperative and follow-up clinical characteristics and
      echocardiography data were analyzed, focusing on left ventricular global/regional
      remodeling and function. Patients were grouped by postoperative ischemic mitral
      regurgitation at 1 year postoperatively: the improved group with no or mild
      ischemic mitral regurgitation and the failure group with moderate or severe
      ischemic mitral regurgitation. Data were compared between the 2 groups to explore
      the predictors of ischemic mitral regurgitation improvement after off-pump
      coronary artery bypass grafting. RESULTS: Five patients died within 1 year and
      were excluded. At the 1-year follow-up, there were 55 patients in the improved
      group and 49 patients in the failure group. Before surgery, the improved group
      had smaller left ventricular end-systolic volume, greater left ventricular
      ejection fraction, greater posterior-inferior volume ratio, and earlier operation
      timing after infarction than the failure group. Posterior-inferior volume ratio
      (P < .001), ejection fraction (P = .003), and duration between infarction and
      operation (P < .001) were independent predictors of preoperative moderate
      ischemic mitral regurgitation improvement. CONCLUSIONS: In selected patients,
      preoperative moderate ischemic mitral regurgitation was relieved by off-pump
      coronary artery bypass grafting. Greater ejection fraction, greater posterior
      inferior volume ratio, and early operation timing after infarction may predict
      the improvement of moderate ischemic mitral regurgitation after off-pump coronary
      artery bypass grafting, suggesting that posterior-inferior regional remodeling,
      reserved ventricular function, and early revascularization are important to the
      outcome.

PMID- 25863935
TI  - To screen or not to screen, that is the question. Or is it?

PMID- 25863936
TI  - Rasagiline and selegiline suppress calcium efflux from mitochondria by PK11195
      induced opening of mitochondrial permeability transition pore: a novel anti
      apoptotic function for neuroprotection.
AB  - Rasagiline and selegiline, inhibitors of type B monoamine oxidase (MAO-B),
      protect neurons from cell death in cellular and animal models. Suppression of
      mitochondrial membrane permeabilization and subsequent activation of apoptosis
      cascade, and induction of anti-apoptotic, pro-survival genes are proposed to
      contribute the anti-apoptotic function. Rasagiline suppresses neurotoxin- and
      oxidative stress-induced membrane permeabilization in isolated mitochondria, but
      the mechanism has been not fully clarified. In this paper, regulation of the
      mitochondrial permeability transition pore by rasagiline and selegiline was
      examined in apoptosis induced by PK11195, a ligand of the outer membrane
      translocator protein 18 kDa (TSPO) in SH-SY5Y cells. The pore opening was
      quantitatively measured using a simultaneous monitoring system for calcium
      (Ca(2+)) and superoxide (O2(-)) (Ishibashi et al. in Biochem Biophys Res Commun
      344:571-580, 2006). The association of the pore opening with Ca(2+) efflux and
      ROS increase was proved by the inhibition of Bcl-2 overexpression and
      cyclosporine A treatment. Potency to release Ca(2+) was correlated with the
      cytotoxicity of TSPO antagonists, PK11195, FGIN-1-27 and protoporphyrin IX,
      whereas a TSPO agonist, 4-chloro-diazepamine, did not significantly increase
      Ca(2+) or cause cell death. Rasagiline and selegiline inhibited mitochondrial
      Ca(2+) efflux through the mitochondrial permeability transition pore dose
      dependently. Ca(2+) efflux was confirmed as the initial signal in mitochondrial
      apoptotic cascade, and the suppression of Ca(2+) efflux may account for the
      neuroprotective function of rasagiline and selegiline. The quantitative
      measurement of Ca(2+) efflux can be applied to determine anti-apoptotic activity
      of neuroprotective compounds. The role of mitochondrial Ca(2+) release in
      neuronal death and also in neuroprotection by MAO-B inhibitors is discussed.

PMID- 25863938
TI  - Transduced PEP-1-heme oxygenase-1 fusion protein reduces remote organ injury
      induced by intestinal ischemia/reperfusion.
AB  - BACKGROUND: A fusion protein composed of heme oxygenase-1 (HO-1) and cell
      penetrating peptide PEP-1 has been shown to reduce local intestinal injury after
      intestinal ischemia/reperfusion (I/R). In this study, we investigated the effects
      of PEP-1-HO-1 fusion protein on remote organ injury induced by intestinal I/R in
      rats. MATERIAL AND METHODS: We randomly assigned 24 male Sprague-Dawley rats to 3
      groups: Sham, I/R, and I/R plus PEP-1-HO-1 treatment (HO). The model of
      intestinal I/R was established by occluding the superior mesenteric artery for 45
      min followed by 120-min reperfusion. In HO group, PEP-1-HO-1 was administered
      intravenously 30 min before ischemia, while animals in the Sham and I/R groups
      received the equal volume of physiological saline. At the end of the experiment,
      lung, liver, and blood samples were collected and analyzed. RESULTS:
      Malondialdehyde levels and histological injury scores were increased, and
      superoxide dismutase activities were decreased in the lung and liver tissues in
      the I/R group compared with the Sham group (P<0.05). Serum levels of alanine
      aminotransferase, aspartate aminotransferase, tumor necrosis factor-alpha,
      interleukin-6, and lung tissue wet weight to dry weight ratio were increased in
      the I/R group compared with the Sham group (P<0.05). NF-kappaB expression in
      intestinal tissues was significantly higher in the I/R group than in the Sham
      group. These changes were significantly reversed by treatment with PEP-1-HO-1.
      CONCLUSIONS: This study demonstrates that administration of PEP-1-HO-1 has a
      protective role against lung and liver injury after intestinal I/R, attributable
      to the reduction of released proinflammatory cytokines regulated by NF-kappaB.

PMID- 25863939
TI  - A premammillary lateral hypothalamic nuclear complex responds to hedonic but not
      aversive tastes in the male rat.
AB  - The lateral hypothalamic area (LHA) has two major roles: arousal/waking and food
      intake controls. Here, it is shown that a premammillary part of the LHA is
      neurochemically and cytoarchitectonically distinct from the tuberal LHA in male
      rats. This part contains nuclear masses, namely the parasubthalamic nucleus and
      the calbindin nucleus, involved in pathways that predict its participation in the
      control of food intake. Analyzing c-Fos expression in experiments related to
      feeding behavior, this region responded specifically to the ingestion of
      palatable nutriments.

PMID- 25863940
TI  - Pharmacodynamic and pharmacokinetic analysis of CNS-active constitutional isomers
      of valnoctamide and sec-butylpropylacetamide--Amide derivatives of valproic acid.
AB  - Valnoctamide (VCD) and sec-butylpropylacetamide (SPD) are CNS-active closely
      related amide derivatives of valproic acid with unique anticonvulsant activity.
      This study evaluated how small chemical changes affect the pharmacodynamics (PD;
      anticonvulsant activity and teratogenicity) and pharmacokinetics (PK) of three
      constitutional isomers of SPD [sec-butylisopropylacetamide (SID) and tert
      butylisopropylacetamide (TID)] and of VCD [tert-butylethylacetamide (TED)]. The
      anticonvulsant activity of SID, TID, and TED was comparatively evaluated in
      several rodent anticonvulsant models. The PK-PD relationship of SID, TID, and TED
      was evaluated in rats, and their teratogenicity was evaluated in a mouse strain
      highly susceptible to teratogen-induced neural tube defects (NTDs). sec
      Butylisopropylacetamide and TID have a similar PK profile to SPD which may
      contribute to their similar anticonvulsant activity. tert-Butylethylacetamide had
      a better PK profile than VCD (and SPD); however, this did not lead to a superior
      anticonvulsant activity. sec-Butylisopropylacetamide and TED did not cause NTDs
      at doses 4-7 times higher than their anticonvulsant ED50 values. In rats, SID,
      TID (ip), and TED exhibited a broad spectrum of anticonvulsant activity. However,
      combined anticonvulsant analysis in mice and rats shows SID as the most potent
      compound with similar activity to that of SPD, demonstrating that substitution of
      the isobutyl moiety in the SPD or VCD molecule by tert-butyl as well as a propyl
      to-isopropyl replacement in the SPD molecule did not majorly affect the
      anticonvulsant activity. 

PMID- 25863941
TI  - Key issues in addressing the comorbidity of depression and pediatric epilepsy.
AB  - Depression is a common comorbidity associated with epilepsy. However, the
      etiology of depression is difficult to establish given the heterogeneity in both
      epilepsy and depression. Nevertheless, the co-occurrence is so common that a
      bidirectional relationship between depression and epilepsy has been theorized.
      Persons with temporal lobe seizure foci and partial-onset epilepsy may be more
      vulnerable to the development of depression. In pediatrics, depression differs
      but may be readily identified by understanding nuances of mood states and
      variability of neurovegetative symptom presentation. Although no clear treatment
      guidance exists in the context of epilepsy, antidepressants have been relatively
      well studied in pediatrics and are effective and well tolerated. Anticonvulsant
      drugs may also improve depressive symptoms though clinical research is lacking in
      pediatrics. Treatment of depression may independently improve outcome for
      epilepsy and for quality of life. Future studies will clarify etiologies of
      depression in the context of epilepsy and improve the evidence base for treatment
      outcomes. 

PMID- 25863942
TI  - Gut stem cells, a story of snails, flies and mice.

PMID- 25863943
TI  - Engineering monocyte-derived dendritic cells to secrete interferon-alpha enhances
      their ability to promote adaptive and innate anti-tumor immune effector
      functions.
AB  - Dendritic cell (DC) vaccination has demonstrated potential in clinical trials as
      a new effective cancer treatment, but objective and durable clinical responses
      are confined to a minority of patients. Interferon (IFN)-alpha, a type-I IFN, can
      bolster anti-tumor immunity by restoring or increasing the function of DCs, T
      cells and natural killer (NK) cells. Moreover, type-I IFN signaling on DCs was
      found to be essential in mice for tumor rejection by the innate and adaptive
      immune system. Targeted delivery of IFN-alpha by DCs to immune cells could boost
      the generation of anti-tumor immunity, while avoiding the side effects frequently
      associated with systemic administration. Naturally circulating plasmacytoid DCs,
      major producers of type-I IFN, were already shown capable of inducing tumor
      antigen-specific T cell responses in cancer patients without severe toxicity, but
      their limited number complicates their use in cancer vaccination. In the present
      work, we hypothesized that engineering easily generated human monocyte-derived
      mature DCs to secrete IFN-alpha using mRNA electroporation enhances their ability
      to promote adaptive and innate anti-tumor immunity. Our results show that IFN
      alpha mRNA electroporation of DCs significantly increases the stimulation of
      tumor antigen-specific cytotoxic T cell as well as anti-tumor NK cell effector
      functions in vitro through high levels of IFN-alpha secretion. Altogether, our
      findings mark IFN-alpha mRNA-electroporated DCs as potent inducers of both
      adaptive and innate anti-tumor immunity and pave the way for clinical trial
      evaluation in cancer patients. 

PMID- 25863947
TI  - Novel 6-(1H-benzo[d]imidazol-2-yl) benzo[a]phenazin-5-ol Derivatives with Dual
      Emission and Large Stokes Shift Synthesis, Photophysical Properties and
      Computational Studies.
AB  - Novel phenazine containing dyes were obtained by the condensation of 5
      hydroxybenzo[a]phenazine-6-carbaldehyde and 5-chloro-benzo[a]phenazine-6
      carbaldehyde with 1,2-diaminobenzene. The dyes were characterized by FT-IR, 1H
      NMR, elemental analysis and mass spectra. The UV-vis absorption and fluorescence
      emission spectra of the dyes were studied in solvents of differing polarity; the
      dyes exhibited excited state intra molecular proton transfer. The structural
      changes due to excited state intramolecular proton transfer (ESIPT) phenomenon in
      terms of bond angle, bond distances and geometry were investigated with the help
      of DFT computations. The computed absorption and emission were in agreement with
      the experimental absorption and emission. 

PMID- 25863944
TI  - Sunitinib dosing schedule 2/1 improves tolerability, efficacy, and health-related
      quality of life in Chinese patients with metastatic renal cell carcinoma.
AB  - PURPOSE: To assess the efficacy and tolerability of sunitinib dosing schedule of
      2 weeks on and 1 week off (schedule 2/1) vs. the traditional schedule of 4 weeks
      on and 2 week off (schedule 4/2) and its influence on health-related quality of
      life (HRQoL) in Chinese patients with metastatic renal cell carcinoma (mRCC).
      MATERIALS AND METHODS: A retrospective analysis of 108 patients with mRCC who
      were treated with sunitinib regimens (50mg daily) between January 2009 and July
      2013 was undertaken. Overall, 3 groups of patients were studied according to the
      dosing schedule they received: schedule 4/2 (n = 50), transitional schedule 2/1
      (T2/1; patients switched from schedule 4/2 to 2/1; n = 26), and initial schedule
      2/1 (I2/1; n = 32). The tumor response, progression-free survival (PFS) time,
      adverse events, and HRQoL were assessed and compared among the groups. RESULTS:
      The incidences of diarrhea, fatigue, hand-foot syndrome, and neutropenia induced
      by the treatment of sunitinib were all significantly less common with schedule
      I2/1 and T2/1 than with schedule 4/2 (P<0.05). Although there was no
      statistically significant difference in the tumor response among the 3 groups,
      the median PFS time was significantly longer with schedule I2/1 than with
      schedules T2/1 and 4/2 (11.2 vs. 9.4 and 9.5mo, respectively, P = 0.030), and
      HRQoL (as determined by 19-item Functional Assessment of Cancer Therapy Kidney
      Symptom Index scores) was better. CONCLUSIONS: Treatment with sunitinib 50mg
      daily using a 2/1 dosing schedule can provide better tolerability and a longer
      PFS with better HRQoL in Chinese patients with mRCC than the traditional schedule
      4/2.

PMID- 25863948
TI  - ECG-derived respiration methods: adapted ICA and PCA.
AB  - Respiration is an important signal in early diagnostics, prediction, and
      treatment of several diseases. Moreover, a growing trend toward ambulatory
      measurements outside laboratory environments encourages developing indirect
      measurement methods such as ECG derived respiration (EDR). Recently,
      decomposition techniques like principal component analysis (PCA), and its
      nonlinear version, kernel PCA (KPCA), have been used to derive a surrogate
      respiration signal from single-channel ECG. In this paper, we propose an adapted
      independent component analysis (AICA) algorithm to obtain EDR signal, and extend
      the normal linear PCA technique based on the best principal component (PC)
      selection (APCA, adapted PCA) to improve its performance further. We also
      demonstrate that the usage of smoothing spline resampling and bandpass-filtering
      improve the performance of all EDR methods. Compared with other recent EDR
      methods using correlation coefficient and magnitude squared coherence, the
      proposed AICA and APCA yield a statistically significant improvement with
      correlations 0.84, 0.82, 0.76 and coherences 0.90, 0.91, 0.85 between reference
      respiration and AICA, APCA and KPCA, respectively. 

PMID- 25863949
TI  - Treatment of pediatric spinal tuberculosis abscess with percutaneous drainage and
      low-dose local antituberculous therapy: a preliminary report.
AB  - OBJECTIVE: The purpose of this study was to evaluate the outcomes of computed
      tomography (CT) guidance using percutaneous catheter with low-dose drainage local
      chemotherapy (modified PCD) and antituberculous therapy (ATT) for the treatment
      of spinal tuberculosis in children. METHODS: Twenty-seven children suffering from
      spinal tuberculosis were treated with modified PCD and ATT in our institute from
      2002 to 2012. We describe our treatment, which involves CT-guided percutaneous
      puncture and local chemotherapy (continuous low-dose (20 mL) irrigation). The
      patients were evaluated based on the Frankel scoring system, the kyphotic Cobb
      angle, and the erythrocyte sedimentation rate (ESR). RESULTS: All patients were
      followed up for an average of 31.00 +/- 13.94 months. No sinus formation was
      detected. All patients responded well to this treatment. The ESR values were
      decreased to normal at last follow-up. The neurological functions show
      significant improvement after operation. Preoperatively, the kyphotic angle was
      22.89 +/- 7.06 degrees , and it was measured as 21.19 +/- 8.73 degrees  at the
      last visit. CONCLUSIONS: Our results showed that percutaneous intubation and low
      dose irrigation under CT guidance (modified percutaneous catheter drainage
      (MPCD)) and ATT are easy, safe, efficient, and less invasive methods for the
      treatment of spinal tuberculosis in children.

PMID- 25863950
TI  - The role of chemotherapy and surgical removal in the treatment of Choroid Plexus
      carcinomas and atypical papillomas.
AB  - INTRODUCTION: We performed a retrospective study on clinical assessment, tumor
      location, radiological imaging, histopathological characteristics, and
      therapeutic management of 7 patients affected by choroid plexus carcinoma (CPC)
      or atypical choroid plexus papilloma (ACPP) who have been observed in the last 12
      years. METHODS: Four patients fulfilled the criteria for classification as ACPP
      and three cases as CPC. The median age of the patients at the diagnosis was 42
      months (range 3-190 months). Except one older patient (15 years old), all
      patients were younger than 3 years of age. In all patients affected by ACPP, a
      total surgical resection was achieved. Two children relapsed 12 and 8 months
      following radical removal. Both of them underwent adjuvant chemotherapy
      (carboplatin, cyclophosphamide, etoposide, doxorubicin, and methotrexate); a
      complete remission was maintained in all cases. In all three patients with CPC,
      it was impossible to achieve complete resection at first surgery. The response to
      chemotherapy was variable: in one case, it was complete with complete remission
      following 6 months; in one case, it was partial with reduction on volume (the
      patient underwent second-look surgery with complete resection); in the third
      case, there was no response and the patient progressed and finally died with
      metastatic disease, 8 months after chemotherapy was started. For children with
      CPC, the OS was 75% at 6 years. RESULTS: In our series, surgery associated with
      chemotherapy led to long-term survival in 4/4 patients affected by ACPP and 2/3
      patients affected by CPC. Clinical results achieved in our series confirm that
      our therapeutic regimen is feasible and efficient as a possible adjuvant
      treatment for both CPC and ACPP. It also suggests that surgery has a pivotal role
      in the management of most children affected by CPTs.

PMID- 25863951
TI  - Fluorescence-guided resection with 5-aminolevulinic acid of meningeal sarcoma in
      a child.
AB  - BACKGROUND: The usefulness of fluorescence-guided resection with 5-aminolevulinic
      acid for malignant brain gliomas was demonstrated by Stummer. However, there are
      several articles in the literature showing the usefulness of the technique for
      other types of tumors, including benign tumors, such as ependymomas or
      meningiomas. Meningeal sarcomas are rare, highly aggressive malignant tumors,
      predominately affecting the pediatric population and have a poor prognosis in
      spite of treatment. Surgical treatment thereof should consist of the most
      complete resection possible. METHODS: In this article, we present the case of a
      seven-year-old boy who received surgical treatment for a left frontal tumor after
      oral administration of 5-aminolevulinic acid (5-ALA); the definitive histological
      diagnosis of which was meningeal sarcoma. The technique was useful for achieving
      a complete resection, as the lesion emitted intense fluorescence, and after
      resection of the lesion with the usual technique, intraoperative fluorescent
      spots were observed in the resection bed that were also tumor. Imaging tests
      performed 5 years after surgery ruled out recurrence of the tumor. CONCLUSION: To
      our knowledge, this is the first case published in the literature of meningeal
      sarcoma in a child in which intraoperative fluorescence with 5-ALA was used to
      achieve a complete resection.

PMID- 25863952
TI  - Treatment of Disseminated Talaromyces marneffei with Tracheal Infection: Two Case
      Reports.
AB  - Talaromyces marneffei infection involving the trachea presents as diffuse
      irregular nodules that grow on the tracheal lumen and/or rarely present as
      concurrent severe eosinophilia. Herein, we report two patients without HIV
      infection whose main tracheal and/or principal bronchi were involved by T.
      marneffei infection, which manifested as diffuse proliferative nodules. In case
      1, the infection primarily affected the main trachea, resulting in structural
      cartilage damage, tracheal stenosis, and tracheal absence. In case 2, there were
      diffuse proliferative nodules in the trachea and bronchi with marked
      eosinophilia. The final diagnosis was made based on a positive culture from
      bronchiolar lavage fluid, skin, and tracheal polyps. Case 1 was administered
      antifungal treatment combined with surgery, but relapse occurred during a 3-month
      follow-up period. Case 2 was treated by intravenous liposomal amphotericin B
      combined with atomized inhaled liposomal amphotericin B, and he later showed
      improvement; there was no relapse during the 12-month period of antifungal
      treatment. Importantly, atomized inhaled amphotericin B antifungal treatment for
      T. marneffei infection has never been previously reported.

PMID- 25863953
TI  - Effect of days in feedlot on growth performance, carcass and meat quality
      attributes of Tanzania shorthorn zebu steers.
AB  - A study was conducted on 50 steers (183 +/- 4 kg initial body weight, 3 years of
      age) to assess effects of days in feedlot on performance, carcass characteristics
      and meat quality of Tanzania shorthorn zebu (TSZ) cattle with the aim of
      determining appropriate finishing period. Periods were 0 day (P0), 25 days (P25),
      50 days (P50), 75 days (P75) and 100 days (P100) with 10 animals per period.
      Steers were housed in individual pens, fed with a concentrate diet and hay on an
      ad libitum basis except the P0 group which was slaughtered at the beginning of
      trial. Long stay in feedlot, P100, increased concentrate dry matter intake by 2
      kg DM/day over short stay, P25. Final weight and total gain increased (P < 0.05)
      from P25 (22.6 kg) to P100 steers (95.4 kg). Periods had no influence (P > 0.05)
      on an average daily gain (ADG) and feed conversion ratio (FCR) but affected
      carcass characteristics. Empty body weight (EBW) and hot carcass weight (HCW)
      increased by 61 and 65 %, respectively, from no feedlot, P0 to P100. Dressing
      percentage was high (P < 0.05) for P100 steers. Carcass measurements, internal
      fat, fat thickness and carcass total fat were the highest (P < 0.05) on P100
      steers and the lowest on P0 steers. Rate of pH decline increased with days in
      feedlot, while cooking loss and shear force values decreased in advanced ageing
      time. Feedlot periods of 75 and 100 days resulted into high intake, carcass
      measurements and tenderness, but 100 days further increased carcass fatness and
      fat thickness levels, thus, with this particular feeding system and animal's
      condition, 75 days is the recommended period to finish TSZ cattle in feedlots. 

PMID- 25863954
TI  - Evaluation of local energy sources in milk production in a tropical silvopastoral
      system with Erythrina poeppigiana.
AB  - An experiment was carried out to determine the effect of four local energy
      sources (sorghum grain, green banana, polished rice, and sugarcane molasses) fed
      to dairy cows on intake, milk production and composition, and economic viability
      in a silvopastoral system in Costa Rica (Turrialba). Twelve grazing cows (Jersey
      * Central American Milking Creole), with a mean live weight of 332 kg (SD 34),
      were supplemented with 0.5 kg of dry matter (DM)/100 kg/LW of Erythrina
      porppigiana fresh foliage daily. Experimental design was a replicated change-over
      4 * 4 Latin Square. The pasture composition was 11 and 17 % of star grass
      (Cynodon niemfuensis), 32 and 28 % of ruzzi grass (Brachiaria rusisiensis), and
      45 and 42 % of natural grasses (Axonopus compresus and Paspalum conjugatum) at
      initial and final times of the essay, respectively. The grass allowance was 30.14
      DM/cow/day. Significant differences were found among treatments for variable milk
      fat content (P < 0.05). Sorghum presented the highest (41.2 g/kg milk) content of
      milk fat, followed by green banana (39.2 g/kg milk), polished rice (38.3 g/kg
      milk) and molasses (38.1 g/kg milk). Non-significant differences (P > 0.05)
      resulted for total milk production (sorghum 9.0 kg/cow/day; green banana 8.9
      kg/cow/day; polished rice 8.8 kg/cow/day; molasses 8.6 kg/cow/day) and fat
      corrected milk (FCM). The financial analysis showed that all treatments were
      economically viable; however, supplementation with green bananas and molasses
      were the most favorable due to the low costs incurred. 

PMID- 25863955
TI  - Assessment of raw milk quality and stakeholders' awareness on milk-borne health
      risks in Arusha City and Meru District, Tanzania.
AB  - A cross-sectional study was conducted to assess the quality of raw milk and
      stakeholders' awareness on milk-borne health risks and factors for poor milk
      hygiene in Arusha City and Meru District, Tanzania between October and December
      2012. A total of 105 smallholder dairy farmers, milk vendors and milk retailers
      were interviewed, and milk samples were collected for physical, microbial and
      antibiotic residue analysis using standard procedures. Questionnaire results
      indicated high level of awareness (94 %) that drinking raw milk can predispose
      consumers to milk-borne diseases; nevertheless, 65 % of respondents consumed raw
      milk. Physicochemical analyses showed some of the milk had sediments (20 %), bad
      smell (21 %) and had clotted on alcohol test (27 %). About 36 % of milk samples
      had pH below 6.6, and 25 % had specific gravity below 1.028 g/ml. The mean total
      viable count (TVC) of milk from vendors is significantly (P < 0.05) higher than
      that from retailers and smallholder dairy farmers. Generally, 65 % of milk
      samples assessed had a higher TVC than the level recommended (2.0 * 10(5) cfu/ml)
      by the East African Community (EAC) standards. Up to 91 % of the milk samples had
      bacterial growth that included Eschericia coli (66 %), Staphylococcus aureus (33
      %), Corynebacterium (11 %) and Pseudomonas (10 %). All smallholder dairy farmers
      were aware of drug residues, but majority (57 %) were unaware of human health
      effects caused by veterinary drug residues in milk. Up to 97 % of respondents
      reported to comply with drug withdrawal periods. This possibly led to all milk
      samples analysed to be negative from detectable levels of antibiotic residues. It
      is concluded that the level of awareness on milk quality is high, although
      practices associated with milking and post-harvest handling predispose milk to
      bacterial contamination which is a public health risk to milk consumers. 

PMID- 25863956
TI  - Synchronization of ovulation with human chorionic gonadotropin in lactating dairy
      cows with ovarian cysts during heat stress.
AB  - A study was conducted during hot season to determine the effect of
      synchronization of ovulation with human chorionic gonadotropin (hCG) on fertility
      of lactating dairy cows with ovarian cysts. Non cyclic Holstein dairy cows (n =
      80) were stratified by parity and diagnosed as having an ovarian cyst. The cows
      were further identified as follicular or luteal cysts according to the plasma
      progesterone (P4) concentration and the cystic image of ultrasonography. Cystic
      cows were randomly assigned to receive treatments (Ovsynch as the control or
      Ovsynch plus 3000 IU hCG). All cows were artificially inseminated at 16-18 h
      after the second gonadotropin releasing hormone injection. Cows supplemented with
      hCG had a greater number of corpus luteum (1.8 +/- 0.2 and 0.8 +/- 0.3; P < 0.05)
      and had greater P4 concentration on day 12 than those control cows (6.3 +/- 0.3
      and 3.9 +/- 0.4 ng/ml; P < 0.05). Concentration of cortisol did not differ
      between groups of cystic cows. No significant differences were found in overall
      conception rates between the treatments; however, significantly greater
      conception rate (P = 0.03) was observed in cows with luteal cysts receiving
      Ovsynch plus hCG. This study highlights that administration of hCG following the
      Ovsynch-based timed artificial insemination (AI) is more effective than the
      control Ovsynch by which the hCG affects corpus luteum (CL) development, P4
      concentration, and thus improves conception rate in dairy cows with luteal cysts.

PMID- 25863957
TI  - Sero-prevalence of Contagious Bovine Pleuropneumonia (CBPP) in bulls originated
      from Borena pastoral area of Southern Ethiopia.
AB  - Contagious Bovine Pleuropneumonia (CBPP) is a highly infectious cattle disease,
      which is widespread in pastoral areas of Africa, and it imposes a major problem
      on Ethiopian livestock export market. Cross-sectional study was conducted in 2011
      on bulls originated from Borena pastoral area to determine seroprevalence of
      CBPP. Forty batches of bulls containing 38,187 Borana bulls were tested using c
      ELISA. Of the total 40 batches tested for the presence of antibodies, 25 (62.5 %)
      of them contained at least one seropositive bull. From the total of 38,187 bulls
      tested, 150 (0.4 %) bulls were positive. The number of seropositive animals
      increases as the herd size increases (P < 0.05). Both at herd and individual
      level, the highest CBPP prevalence was recorded in herd size >1000, and the
      difference was found statistically significant (P < 0.05). There was
      statistically significant (chi (2) = 23.73, df = 9, P = 0.005) difference of CBPP
      prevalence between months of the year. The present low prevalence of CBPP in the
      cattle feedlots indicates that the disease is decreasing progressively in Borena
      pastoral area, this might be associated with the ongoing mass vaccination
      campaign against economically important livestock diseases in pastoral areas. The
      decrease in the prevalence of CBPP offered a great opportunity to livestock
      producers and live animal and meat exporters by improving the demand of Ethiopian
      livestock on international market. Regular reintroduction of infected cattle from
      neighboring countries or herds where the disease remains endemic may change the
      disease dynamics again. Therefore, mass blanket vaccinations coupled with prompt
      diagnosis, isolation and stamping out of the outbreaks, intensive surveillance,
      followed by strict cattle movement control should be implemented by concerned
      parties. 

PMID- 25863958
TI  - The epidemiology of malignant catarrhal fever (MCF) and contribution to cattle
      losses in farms around Rhodes Matopos National Park, Zimbabwe.
AB  - Malignant catarrhal fever (MCF) is a fatal viral disease of cattle prevalent in
      farms bordering wildlife conservancies and national parks where cattle and
      wildebeests cohabit. The behaviour of the diseases and its related contribution
      to cattle mortalities has been poorly studied in the smallholder sector. A study
      was therefore conducted to established trends of occurrence and contribution to
      animal losses in 97 smallholder farms and eight commercial farms bordering Rhodes
      Matopos National Park (RMNP). A structured questionnaire and secondary records
      were used to gather the data in the smallholder and commercial farms,
      respectively. In the smallholder sector, cattle farmers from three villages were
      chosen as respondents in a survey to provide information on the impact and extent
      of losses in their cattle herds. Epidemiological data from January 2006 to April
      2014 was extracted from farm records from two Matopos Research Institute farms. A
      seasonal pattern in MCF occurrence was observed. Most cattle mortalities were
      recorded during summer (February to May), with highest mortalities recorded from
      March to April. Sporadic cases were however recorded in October and November in
      year 2007, 2010, and 2012. The study further revealed that MCF caused 71 and 21 %
      of cattle mortalities in the commercial and smallholder sector, respectively.
      Deferred grazing of wildebeest hotspots by restriction of cattle movement during
      summer or November to April period avoids wildebeest-cattle contact. This can
      alleviate cattle mortalities due to MCF. 

PMID- 25863959
TI  - Effect of browse plant foliage supplementation on the performance of buckling
      goats fed threshed sorghum top basal diet.
AB  - The effect of browse plants (Piliostigma thonningii, Daniellia oliveri, Afzelia
      africana, Pterocarpus erinaceus and Annona senegalensis) supplementation on
      nutrient intake, digestibility, nutritive value and N utilization and growth
      performance of buckling goats fed threshed sorghum top (TST) was investigated
      using 24 Red Sokoto goats (9.0 +/- 0.25 kg) body weight (BW) which were randomly
      assigned to one of the six diets in a completely random design. Intakes of dry
      matter (DM) and nutrients, feed conversion ratio, digestibility of nutrients
      except for neutral detergent fibre (NDF) and acid detergent fibre (ADF),
      digestible organic matter (DOM), digestible crude protein (DCP), energy
      concentration, N utilization and average daily gain were superior (P < 0.05) in
      TST-supplemented diets compared to sole TST diet. Among the supplemental fodders,
      intakes of forage, DM, condensed tannins and most of the nutrients; digestibility
      of DM, crude protein (CP) and non-fibre carbohydrate, DOM and DCP; and N
      absorbed, balance and retention were greater (P < 0.05) in A. africana relative
      to the other fodders. Results indicate that the entire browse fodders are good
      supplements to low quality TST, though A. africana appears to have a better
      nutritive value.

PMID- 25863962
TI  - Rules of providing cord blood for induced pluripotent stem cells for research.

PMID- 25863961
TI  - G9a-Mediated Regulation of OXT and AVP Expression in the Basolateral Amygdala
      Mediates Stress-Induced Lasting Behavioral Depression and Its Reversal by
      Exercise.
AB  - Chronic stress produces behavioral depression. Conversely, physical exercise is
      held to be beneficial in the treatment of depression. Although genomic mechanisms
      are likely involved in these behavioral changes, underlying mechanisms are not
      clearly understood. In the present study, we investigated whether stress effects
      and their reversal by exercise occur via genomic mechanisms in the amygdala, a
      core part of the limbic system important for regulating mood states. Mice treated
      with chronic restraint showed lasting depression-like behaviors, which were
      counteracted by treatment with scheduled forceful exercise. Microarray analysis
      identified a number of genes whose expression in the amygdala was either
      upregulated or downregulated after repeated stress, and these changes were
      reversed by exercise. Of these genes, the neuropeptides oxytocin (OXT) and
      arginine vasopressin (AVP) were selected as representative stress-induced and
      exercise-responded genes in the BLA. Stereotaxic injection of OXT or AVP receptor
      agonists within the BLA in normal mice produced depression-like behaviors,
      whereas small interfering RNA (siRNA)-mediated suppression of the OXT or AVP
      transcripts in the BLA was sufficient to block stress-induced depressive
      behaviors. Stress-induced depression-like behaviors were accompanied by a global
      reduction of G9a histone methyltransferase and H3K9me2 at the OXT and AVP
      promoters. Conversely, repeated exercise increased the levels of G9a and H3K9me2
      at the OXT and AVP promoters in the BLA, which was associated with the
      suppression of OXT and AVP expressions. These results identify G9a-induced
      histone methylation at the OXT and AVP promoters in the BLA as a mechanism for
      mediating stress-induced lasting behavioral depression and its reversal by
      exercise.

PMID- 25863960
TI  - Therapeutical Strategies for Spinal Cord Injury and a Promising Autologous
      Astrocyte-Based Therapy Using Efficient Reprogramming Techniques.
AB  - Spinal cord injury (SCI) is a traumatic event resulting in disturbances to normal
      sensory, motor, or autonomic functions, which ultimately impacts a patient's
      physical, psychological, and social well-being. Until now, no available therapy
      for SCI can effectively slow down or halt the disease progression. Compared to
      traditional treatments, e.g., medication, surgery, and functional electrical
      stimulation, stem cell replacement therapy shows high potential for repair and
      functional plasticity. Thus, stem cell therapy may provide a promising strategy
      in curative treatment of SCI, specifically when considering the requirement of
      neuron replenishment in the spinal cord after distinct acute injuries. However,
      the therapeutic application of neural stem cells (NSCs) still faces enormous
      challenges, such as ethical issues, possible inflammatory reactions, graft
      rejection, and tumor formation. Therefore, it is of vital interest to identify
      more suitable sources of cells with stem cell potential, which might potentially
      be harnessed for local neural repair. Due to abovementioned possible drawbacks,
      these cells should be autologous. Reprogramming of astrocytes to generate the
      desired neuronal cell types would open the door to autologous cell
      transplantation and treatment of SCI without possible severe side effects. In
      this paper, we review the relevant therapeutic strategies for SCI, and conversion
      of astrocyte into NSCs, suggesting this procedure as a possible treatment option.

PMID- 25863964
TI  - A quantitative measure of conformational changes in Apo, holo and ligand bound
      form of enzymes.
AB  - Determination of the native geometry of the enzymes and ligand complexe is a key
      step in the process of structure based drug designing. Enzymes and ligands show
      flexibility in structural behavior as they come in contact with each other. When
      ligand binds with active site of the enzyme, in presence of cofactor some
      structural changes are expected to occur in the active site. Motivation behind
      this study is to determine the nature of conformational changes as well as
      regions where such changes are more pronounced. To measure the structural changes
      due to cofactor and ligand complex, enzyme in Apo, holo and ligand bound form is
      selected. Enzyme data set was retrieved from protein data bank (PDB). 15 triplet
      groups were selected for the analysis of structural changes based on selection
      criteria. Structural features for selected enzymes were compared at the global as
      well as local region. Accessible surface area for the enzymes in entire triplet
      set was calculated, which describes the change in accessible surface area upon
      binding of cofactor and ligand with the enzyme. It was observed that some
      structural changes take place during binding of ligand in presence of cofactor.
      This study will helps in understanding the level of flexibility in protein-ligand
      interaction for computer aided drug designing.

PMID- 25863963
TI  - Cell type-dependent variation in paracrine potency determines therapeutic
      efficacy against neonatal hyperoxic lung injury.
AB  - BACKGROUND AIMS: The aim of this study was to determine the optimal cell type for
      transplantation to protect against neonatal hyperoxic lung injury. To this end,
      the in vitro and in vivo therapeutic efficacies and paracrine potencies of human
      umbilical cord blood-derived mesenchymal stromal cells (HUMs), human adipose
      tissue-derived mesenchymal stromal cells (HAMs) and human umbilical cord blood
      mononuclear cells (HMNs) were compared. METHODS: Hyperoxic injury was induced in
      vitro in A549 cells by challenge with H2O2. Alternatively, hyperoxic injury was
      induced in newborn Sprague-Dawley rats in vivo by exposure to hyperoxia (90%
      oxygen) for 14 days. HUMs, HAMs or HMNs (5 * 10(5) cells) were given
      intratracheally at postnatal day 5. RESULTS: Hyperoxia-induced increases in in
      vitro cell death and in vivo impaired alveolarization were significantly
      attenuated in both the HUM and HAM groups but not in the HMN group. Hyperoxia
      impaired angiogenesis, increased the cell death and pulmonary macrophages and
      elevated inflammatory cytokine levels. These effects were significantly decreased
      in the HUM group but not in the HAM or HMN groups. The levels of human vascular
      endothelial growth factor and hepatocyte growth factor produced by donor cells
      were highest in HUM group, followed by HAM group and then HMN group. CONCLUSIONS:
      HUMs exhibited the best therapeutic efficacy and paracrine potency than HAMs or
      HMNs in protecting against neonatal hyperoxic lung injury. These cell type
      dependent variations in therapeutic efficacy might be associated or mediated with
      the paracrine potency of the transplanted donor cells.

PMID- 25863965
TI  - jEcho: an evolved weight vector to characterize the protein's post-translational
      modification motifs.
AB  - Protein's post-translational modification (PTM) represents a major dynamic
      regulation of protein functions after the translation of polypeptide chains from
      mRNA molecule. Compared with the costly and labor intensive wet lab
      characterization of PTMs, the computer-based detection of PTM residues has been a
      major complementary technique in recent years. Previous studies demonstrated that
      the PTM-flanking positions convey different contributions to the computational
      detection of PTM residue, but did not directly translate this observation into
      the in silico PTM prediction. We propose a weight vector to represent the variant
      contributions of the PTM flanking positions, and use an evolutionary algorithm to
      optimize the vector. Even a simple nearest neighbor algorithm with the
      incorporated optimal weight vector outperforms the currently available
      algorithms. The algorithm is implemented as an easy-to-use computer program,
      jEcho version 1.0. The implementation language, Java, makes jEcho platform
      independent and visually interactive. The predicted results may be directly
      exported as publication-quality images or text files. jEcho may be downloaded
      from http://www.healthinformaticslab.org/supp/ .

PMID- 25863966
TI  - miRNA-mRNA interaction network in non-small-cell lung cancer.
AB  - MicroRNAs (miRNA) are small RNA molecules, about 20-25 nucleotides in length.
      They repress or degrade messenger RNA (mRNA) translation, which are involved in
      human cancer. In this study based on paired miRNA and mRNA expression profiles of
      non-small-cell lung cancers (NSCLC) samples, we constructed and analyzed miRNA
      mRNA interaction network via several bioinformatics softwares and platforms. This
      integrative network is comprised of 249 nodes for mRNA, 90 nodes for miRNA and
      290 edges that show regulations between target genes and miRNAs. The three miR
      1207-5p, miR-1228* and miR-939 are the most connected miRNA that regulated a
      large number of genes. ST8SIA2, MED1 and HDAC4, SPN, which are targeted by
      multiple miRNAs and located in the center of the network, are involved in both
      lung cancer and nervous system via functional annotation analysis. Such a global
      interaction network of miRNA-mRNA in lung cancer will contribute to refining
      miRNA target predictions and developing novel therapeutic candidates.

PMID- 25863967
TI  - Hypoxia limits mouse follicle growth in vitro.
AB  - Ovarian follicle culture is useful for elucidation of factors involved in the
      regulation of follicular function. We examined the effects of gas phase oxygen
      concentration, an oil overlay, serum type and medium supplementation with FSH,
      insulin-transferrin-selenium (ITS) and l-ascorbic acid on cultured preantral
      mouse follicle growth in a spherical, non-attached follicle culture system.
      Follicle growth in 5% oxygen was significantly (P < 0.01) inferior to growth in
      20% oxygen in terms of follicle diameter. This was likely due to hypoxia, as
      evidenced by significantly (P < 0.05) increased follicle secretion of vascular
      endothelial growth factor (VEGF), a marker of cell hypoxia. Follicular growth was
      not (P > 0.05) affected by an oil overlay, ITS supplementation or serum type.
      Culture in medium with 5% mouse serum, 1 IU mL-1 FSH, 25 MUg mL-1 l-ascorbic acid
      and 20% oxygen without an oil overlay supported the growth of follicles to a
      maximum diameter of 380 MUm in 6 days. Compared with mature preovulatory mouse
      follicles in vivo that often have diameters >500 MUm within the same time frame,
      in vitro-grown follicles clearly exhibit limited growth. Thus, adequate
      oxygenation is an essential factor in the process of optimising follicle growth.

PMID- 25863968
TI  - Protective immune responses in ducklings induced by a suicidal DNA vaccine of the
      sigma C gene of novel duck reovirus.
AB  - A suicidal DNA vaccine based on a Semliki Forest virus (SFV) replicon was
      evaluated for the development of a vaccine against novel duck reovirus (NDRV).
      The sigma C gene of NDRV was cloned and inserted into pSCA1, an SFV DNA-based
      replicon vector. After transfected into BHK-21 cells, the antigenicity of the
      sigma C protein was confirmed using an indirect immunofluorescence and Western
      blot assay. Immunogenicity was studied in ducklings. The results showed that NDRV
      specific antibodies, neutralizing antibodies, IFN-gamma and IL-4 were well
      induced in ducklings. Furthermore, all of the ducklings were protected against
      challenge with wild-type NDRV. 

PMID- 25863969
TI  - Erratum to: The L450F [Corrected] mutation in KCND3 brings spinocerebellar ataxia
      and Brugada syndrome closer together.

PMID- 25863970
TI  - Editorial on the European Society of Gastrointestinal Endoscopy (ESGE) and
      European Society of Gastrointestinal and Abdominal Radiology (ESGAR) guideline on
      clinical indications for CT colonography in the colorectal cancer diagnosis.
AB  - European Society of Gastrointestinal Endoscopy (ESGE)-European Society of
      Gastrointestinal and Abdominal Radiology (ESGAR) guideline was generated jointly
      by a team of researchers, including gastrointestinal radiologists and
      endoscopists, and represents the first full collaborative effort between the two
      specialties after years of turf battles involving CT colonography (CTC) and
      colonoscopy (CS). This guideline has a main educational purpose and it represents
      the attempt to find a consensus about the use of CTC in clinical practice based
      on the best current available evidence. Thus, it should not be considered as
      rules for establishing a legal standard of care. Main recommendations include the
      use of CTC as the radiological examination of choice for the diagnosis of
      colorectal neoplasia, the use of CTC in the case of incomplete CS, and the
      possible use of CTC as an acceptable and equally sensitive alternative for
      patients with symptoms suggestive of colorectal cancer (CRC), when CS is
      contraindicated or not possible. ESGE-ESGAR guideline does not recommend CTC for
      population screening, but considers that CTC may be proposed as a CRC screening
      test on an individual basis (opportunistic screening) provided the screenee is
      adequately informed about test characteristics, benefits and risks. With regard
      to patient management, referral for endoscopic polypectomy in patients with at
      least one polyp >= 6 mm in diameter detected at CTC is recommended, considering
      surveillance only in case polyp removal is not possible. Knowledge about CTC is
      in continuous evolution and this means that a revision might be necessary in the
      future as new data appear.

PMID- 25863971
TI  - Cardiopulmonary Limitation in Hypertrophic Cardiomyopathy: Unscrambling the
      Rubik's Cube.

PMID- 25863972
TI  - Cardiopulmonary responses and prognosis in hypertrophic cardiomyopathy: a
      potential role for comprehensive noninvasive hemodynamic assessment.
AB  - OBJECTIVES: This study sought to discover the key determinants of exercise
      capacity, maximal oxygen consumption (oxygen uptake [Vo2]), and ventilatory
      efficiency (ventilation/carbon dioxide output [VE/Vco2] slope) and assess the
      prognostic potential of metabolic exercise testing in hypertrophic cardiomyopathy
      (HCM). BACKGROUND: The intrinsic mechanisms leading to reduced functional
      tolerance in HCM are unclear. METHODS: The study sample included 156 HCM patients
      consecutively enrolled from January 1, 2007 to January 1, 2012 with a complete
      clinical assessment, including rest and stress echocardiography and
      cardiopulmonary exercise test (CPET) with impedance cardiography. Patients were
      also followed for the composite outcome of cardiac-related death, heart
      transplant, and functional deterioration leading to septal reduction therapy
      (myectomy or septal alcohol ablation). RESULTS: Abnormalities in CPET responses
      were frequent, with 39% (n = 61) of the sample showing a reduced exercise
      tolerance (Vo2 max <80% of predicted) and 19% (n = 30) characterized by impaired
      ventilatory efficiency (VE/Vco2 slope >34). The variables most strongly
      associated with exercise capacity (expressed in metabolic equivalents), were peak
      cardiac index (r = 0.51, p < 0.001), age (r = -0.25, p < 0.01), male sex (r =
      0.24, p = 0.02), and indexed right ventricular end-diastolic area (r = 0.31, p =
      0.002), resulting in an R(2) of 0.51, p < 0.001. Peak cardiac index was the main
      predictor of peak Vo2 (r = 0.61, p < 0.001). The variables most strongly related
      to VE/VCO2 slope were E/E' (r = 0.23, p = 0.021) and indexed left atrial volume
      index (LAVI) (r = 0.34, p = 0.005) (model R(2) = 0.15). The composite endpoint
      occurred in 21 (13%) patients. In an exploratory analysis, 3 variables were
      independently associated with the composite outcome (mean follow-up 27 +/- 11
      months): peak Vo2 <80% of predicted (hazard ratio: 4.11; 95% confidence interval
      [CI]: 1.46 to 11.59; p = 0.008), VE/Vco2 slope >34 (hazard ratio: 3.14; 95% CI:
      1.26 to 7.87; p = 0.014), and LAVI >40 ml/m(2) (hazard ratio: 3.32; 95% CI: 1.08
      to 10.16; p = 0.036). CONCLUSIONS: In HCM, peak cardiac index is the main
      determinant of exercise capacity, but it is not significantly related to
      ventilatory efficiency. Peak Vo2, ventilatory inefficiency, and LAVI are
      associated with an increased risk of major events in the short-term follow-up.

PMID- 25863974
TI  - Vitamin D Deficiency and Heart Failure Risk: Not so Black and White?

PMID- 25863973
TI  - Race and Vitamin D Binding Protein Gene Polymorphisms Modify the Association of
      25-Hydroxyvitamin D and Incident Heart Failure: The ARIC (Atherosclerosis Risk in
      Communities) Study.
AB  - OBJECTIVES: This study sought to determine if low serum 25-hydroxyvitamin D
      (25[OH]D) is associated with incident heart failure (HF) and if the association
      is: 1) partly mediated by traditional cardiovascular risk factors; 2) stronger
      among whites than blacks; and 3) stronger among those genetically predisposed to
      having high levels of vitamin D binding protein (DBP). BACKGROUND: Suboptimal
      25(OH)D is a potential cardiovascular risk factor. METHODS: A total of 12,215
      ARIC (Atherosclerosis Risk in Communities) study participants free of HF at
      baseline (1990 to 1992; median age, 56; 24% black) were followed through 2010.
      Total serum 25(OH)D was measured at baseline using liquid chromatography-mass
      spectrometry. Incident HF events were identified by a hospital discharge code of
      ICD9-428 and parallel International Classification of Diseases codes for HF
      deaths. RESULTS: During 21 years of follow-up, 1,799 incident HF events accrued.
      The association between 25(OH)D and HF varied by race (p-interaction = 0.02).
      Among whites, risk was 2-fold higher for those in the lowest (<=17 ng/ml) versus
      highest (>=31 ng/ml) quintile of 25(OH)D. The association was attenuated but
      remained significant with covariate adjustment. In blacks there was no overall
      association. In both races, those with low 25(OH)D and the rs7041 G allele, which
      predisposes to high DBP, were at greater risk (p-interaction = 0.01).
      CONCLUSIONS: Low serum 25(OH)D was independently associated with incident HF
      among whites, but not among blacks. However, in both races, low 25(OH)D was
      associated with HF risk among those genetically predisposed to high DBP. These
      findings provide novel insight into metabolic differences that may underlie
      racial variation in the association between 25(OH)D and cardiovascular risk.

PMID- 25863975
TI  - The food environment is a complex social network.
AB  - The lack of demonstrated impact of the South LA fast food ban suggests that the
      policy was too narrowly crafted. Healthy food deserts like South LA are
      simultaneously unhealthy food swamps; and face myriad interrelated social,
      economic, and environmental challenges. The food environment is a complex social
      network impacted by social, economic and political factors at the neighborhood,
      regional, national, and international levels. Banning one subtype of unhealthy
      food venue is not likely to limit the availability of unhealthy processed and
      packaged foods nor result in increased access to affordable healthy foods. Food
      deserts and food insecurity are symptoms of the interacting pathologies of
      poverty, distressed communities, and unhealthy global macroeconomic and
      industrial policies. Policies that seek to impact urban health disparities need
      to tackle root causes including poverty and the global production and
      distribution of cheap, addictive, unhealthy products that promote unhealthy
      lifestyles. 

PMID- 25863976
TI  - Diagnostic accuracy of FEV1/forced vital capacity ratio z scores in asthmatic
      patients.
AB  - BACKGROUND: The FEV1/forced vital capacity (FVC) ratio is used as a criterion for
      airflow obstruction; however, the test characteristics of spirometry in the
      diagnosis of asthma are not well established. The accuracy of a test depends on
      the pretest probability of disease. OBJECTIVE: We wanted to estimate the FEV1/FVC
      ratio z score threshold with optimal accuracy for the diagnosis of asthma for
      different pretest probabilities. METHODS: Asthmatic patients enrolled in 4 trials
      from the Asthma Clinical Research Centers were included in this analysis.
      Measured and predicted FEV1/FVC ratios were obtained, with calculation of z
      scores for each participant. Across a range of asthma prevalences and z score
      thresholds, the overall diagnostic accuracy was calculated. RESULTS: One thousand
      six hundred eight participants were included (mean age, 39 years; 71% female; 61%
      white). The mean FEV1 percent predicted value was 83% (SD, 15%). In a symptomatic
      population with 50% pretest probability of asthma, optimal accuracy (68%) is
      achieved with a z score threshold of -1.0 (16th percentile), corresponding to a 6
      percentage point reduction from the predicted ratio. However, in a screening
      population with a 5% pretest probability of asthma, the optimum z score is -2.0
      (second percentile), corresponding to a 12 percentage point reduction from the
      predicted ratio. These findings were not altered by markers of disease control.
      CONCLUSION: Reduction of the FEV1/FVC ratio can support the diagnosis of asthma;
      however, the ratio is neither sensitive nor specific enough for diagnostic
      accuracy. When interpreting spirometric results, consideration of the pretest
      probability is an important consideration in the diagnosis of asthma based on
      airflow limitation.

PMID- 25863977
TI  - IL-33 impacts on the skin barrier by downregulating the expression of filaggrin.

PMID- 25863978
TI  - Eosinophil apoptosis-inducing drugs risk worsening rather than resolving asthma.

PMID- 25863979
TI  - Reply: To PMID 25497369.

PMID- 25863980
TI  - Clinical laboratories worldwide need to report IgE antibody results on clinical
      specimens as analytical results and not use differential positive thresholds.

PMID- 25863981
TI  - Transcriptome analysis of controlled and therapy-resistant childhood asthma
      reveals distinct gene expression profiles.
AB  - BACKGROUND: Children with problematic severe asthma have poor disease control
      despite high doses of inhaled corticosteroids and additional therapy, leading to
      personal suffering, early deterioration of lung function, and significant
      consumption of health care resources. If no exacerbating factors, such as smoking
      or allergies, are found after extensive investigation, these children are given a
      diagnosis of therapy-resistant (or therapy-refractory) asthma (SA). OBJECTIVE: We
      sought to deepen our understanding of childhood SA by analyzing gene expression
      and modeling the underlying regulatory transcription factor networks in
      peripheral blood leukocytes. METHODS: Gene expression was analyzed by using Cap
      Analysis of Gene Expression in children with SA (n = 13), children with
      controlled persistent asthma (n = 15), and age-matched healthy control subjects
      (n = 9). Cap Analysis of Gene Expression sequencing detects the transcription
      start sites of known and novel mRNAs and noncoding RNAs. RESULTS: Sample groups
      could be separated by hierarchical clustering on 1305 differentially expressed
      transcription start sites, including 816 known genes and several novel
      transcripts. Ten of 13 tested novel transcripts were validated by means of RT-PCR
      and Sanger sequencing. Expression of RAR-related orphan receptor A (RORA), which
      has been linked to asthma in genome-wide association studies, was significantly
      upregulated in patients with SA. Gene network modeling revealed decreased
      glucocorticoid receptor signaling and increased activity of the mitogen-activated
      protein kinase and Jun kinase cascades in patients with SA. CONCLUSION:
      Circulating leukocytes from children with controlled asthma and those with SA
      have distinct gene expression profiles, demonstrating the possible development of
      specific molecular biomarkers and supporting the need for novel therapeutic
      approaches.

PMID- 25863982
TI  - Comparability, diagnostic validity and completeness of Nigerian cancer
      registries.
AB  - BACKGROUND: Like many countries in Africa, Nigeria is improving the quality and
      coverage of its cancer surveillance. This work is essential to address this
      growing category of chronic diseases, but is made difficult by economic,
      geographic and other challenges. PURPOSE: To evaluate the completeness,
      comparability and diagnostic validity of Nigeria's cancer registries. METHODS:
      Completeness was measured using children's age-specific incidence (ASI) and an
      established metric based on a modified Poisson distribution with regional
      comparisons. We used a registry questionnaire as well as percentages of death
      certificate-only cases, morphologically verified cases, and case registration
      errors to examine comparability and diagnostic validity. RESULTS: Among the
      children's results, we found that over half of all cancers were non-Hodgkin
      lymphoma. There was also evidence of incompleteness. Considering the regional
      completeness comparisons, we found potential evidence of cancer-specific general
      incompleteness as well as what appears to be incompleteness due to inability to
      diagnose specific cancers. We found that registration was generally comparable,
      with some exceptions. Since autopsies are not common across Nigeria, coding for
      both them and death-certificate-only cases was also rare. With one exception,
      registries in our study had high rates of morphological verification of female
      breast, cervical and prostate cancers. CONCLUSIONS: Nigeria's registration
      procedures were generally comparable to each other and to international
      standards, and we found high rates of morphological verification, suggesting high
      diagnostic validity. There was, however, evidence of incompleteness.

PMID- 25863983
TI  - Low alveolar and bronchial nitric oxide in severe uncomplicated obesity.
AB  - BACKGROUND: Fractional concentration of exhaled nitric oxide (FeNO) is a
      recognized biomarker of the lower respiratory tract, where it is produced by the
      proximal conducting airways and the expansible peripheral bronchoalveolar
      compartment. We have previously shown that large increase in body mass decreases
      FeNO. Here we evaluated bronchial and alveolar components of the NO output of the
      lower respiratory tract in subjects with severe uncomplicated obesity (OB).
      METHODS: Fifteen OB subjects (BMI 45.3 +/- 5.6 kg/m(2)), 15 healthy controls (HC)
      (BMI 22.4 +/- 2.4 kg/m(2)) and 10 obese subjects who experienced weight loss
      after bariatric surgery (OBS) (BMI 31.2 +/- 3.4 kg/m(2)), were examined.
      Anthropometry and respiratory lung tests were performed. Exhaled NO was assessed
      using multiple single-breath NO analysis at different constant expiratory flow
      rates. From the fractional NO concentration measured at each flow-rate, the total
      NO flux between tissue and gas phase in the bronchial lumen (J'awNO), and the
      alveolar NO concentration (CANO) were extrapolated. RESULTS: Measured FeNO levels
      at 50 mL/s were lower in OB compared with HC and OBS (11.6 +/- 2.8 ppb, 18.0 +/-
      4.1 ppb and 17.6 +/- 2.9 ppb, respectively, p < 0.05). In OB, both J'awNO and
      CANO resulted significantly lower than OBS and HC values. CONCLUSIONS:
      Respiratory NO output is decreased in severe uncomplicated obesity for the
      reduction of both large/central airway maximal NO flux and alveolar NO
      concentration. The pathophysiological relevance of airway NO abnormalities in
      severe obese phenotype remains to be investigated.

PMID- 25863984
TI  - Differences in correlates of energy balance in normal weight, overweight and
      obese adults.
AB  - PURPOSE: The purpose of this study was to examine differences in total daily
      energy expenditure (TDEE), energy expenditure in various intensities, as well as
      total daily energy intake (TDEI) and diet quality in normal weight, overweight
      and obese men and women. Further, the association of energy expenditure and
      energy intake with body fatness was examined. METHODS: The cross-sectional
      analysis included 430 adults (27.7 +/- 3.8 years; 49.3% male). Body weight and
      height were measured according to standard procedures and percent body fat (BF)
      was assessed via dual X-ray absorptiometry. Energy expenditure was determined via
      the SenseWear Armband. Energy intake and the Healthy Eating Index (HEI) were
      calculated based on multiple 24-h recalls. RESULTS: Weight adjusted TDEI and TDEE
      were significantly lower in overweight and obese adults compared to their normal
      weight peers (p < 0.001) and obese women had a lower HEI (p = 0.006). Overweight
      and obese adults further displayed a higher proportion of energy expenditure
      spent in sedentary and in light activities (p < 0.001), while the proportion of
      energy expenditure in moderate-to-vigorous physical activity (MVPA) was lower
      compared to their normal weight peers (p < 0.001). The inverse relationship
      between BMI or BF and MVPA was stronger than the positive association between BMI
      or BF and the proportion of energy expended in sedentary or light pursuits (r MPA
      = -0.45 to -0.67/r MVPA = -0.51 to -0.66 vs. r Sedentary = 0.33 to 0.52/r light =
      0.36 to 0.47; p < 0.001). CONCLUSIONS: These findings emphasise the importance of
      MPA and bouts of MVPA regarding the maintenance of a normal body weight.

PMID- 25863985
TI  - Direct effects of fatty meals and adiposity on oxidised low-density lipoprotein.
AB  - High-fat intake and high adiposity contribute to hyperlipaemia. In a
      hyperlipaemic state, lipoproteins infiltrate arterial wall where they are
      modified and cause an immune response characteristic of atherosclerosis. A small
      fraction of modified lipoproteins including oxidised low-density lipoprotein (ox
      LDL) returns to circulation. The present study tracked high-fat meals during four
      weeks as to find effects of sustained frequency change on adiposity and ox-LDL.
      The findings indicated that changes in frequency of consumption of high-fat
      eating episodes correlated directly with changes in adiposity and ox-LDL. Hence
      the number of fatty meals consumed by people with overweight or obesity in few
      weeks could affect the atherogenic process. 

PMID- 25863986
TI  - A semi-supervised learning framework for biomedical event extraction based on
      hidden topics.
AB  - OBJECTIVES: Scientists have devoted decades of efforts to understanding the
      interaction between proteins or RNA production. The information might empower the
      current knowledge on drug reactions or the development of certain diseases.
      Nevertheless, due to the lack of explicit structure, literature in life science,
      one of the most important sources of this information, prevents computer-based
      systems from accessing. Therefore, biomedical event extraction, automatically
      acquiring knowledge of molecular events in research articles, has attracted
      community-wide efforts recently. Most approaches are based on statistical models,
      requiring large-scale annotated corpora to precisely estimate models' parameters.
      However, it is usually difficult to obtain in practice. Therefore, employing un
      annotated data based on semi-supervised learning for biomedical event extraction
      is a feasible solution and attracts more interests. METHODS AND MATERIAL: In this
      paper, a semi-supervised learning framework based on hidden topics for biomedical
      event extraction is presented. In this framework, sentences in the un-annotated
      corpus are elaborately and automatically assigned with event annotations based on
      their distances to these sentences in the annotated corpus. More specifically,
      not only the structures of the sentences, but also the hidden topics embedded in
      the sentences are used for describing the distance. The sentences and newly
      assigned event annotations, together with the annotated corpus, are employed for
      training. RESULTS: Experiments were conducted on the multi-level event extraction
      corpus, a golden standard corpus. Experimental results show that more than 2.2%
      improvement on F-score on biomedical event extraction is achieved by the proposed
      framework when compared to the state-of-the-art approach. CONCLUSION: The results
      suggest that by incorporating un-annotated data, the proposed framework indeed
      improves the performance of the state-of-the-art event extraction system and the
      similarity between sentences might be precisely described by hidden topics and
      structures of the sentences.

PMID- 25863987
TI  - Efficiency of antifreeze glycoproteins for cryopreservation of Nili-Ravi (Bubalus
      bubalis) buffalo bull sperm.
AB  - Experiments were conducted to evaluate the effect of Antarctic fish antifreeze
      glycoproteins, (AFGP) size 1-5 (34-10.5 kDa) and 7-8 (3.2 and 2.4 kDa) in
      extender on buffalo bull sperm at cooling (4  degrees C) and at post thawing.
      Semen was collected from three Nili-Ravi buffalo bulls with artificial vagina for
      3 weeks. Qualifying ejaculates from each buffalo bull were diluted (at 37 
      degrees C having 50*10(6) sperm/mL) in tris-citric acid extender containing AFGP
      at 0 (control), 0.1, 1 and 10 MUg/mL. An aliquot of diluted semen was evaluated
      for sperm progressive motility and plasma membrane integrity, while the remaining
      fraction was cooled to 4  degrees C in 2 h. Further, an aliquot of cooled semen
      was evaluated for the previously described variables and the remaining fraction
      was cryopreserved (-196  degrees C). After 24 h of storage, straws were thawed at
      37  degrees C for 30 s to assess post-thaw sperm quality. Inclusion of AFGP in
      the extender did not affect (P>0.05) sperm progressive motility and plasma
      membrane integrity of buffalo bull sperm at cooling stage (4  degrees C).
      However, at post thawing, improvement (P<0.05) in sperm progressive motility and
      plasma membrane integrity was recorded in extender containing AFGP 1-5 and AFGP 7
      8 at 1 MUg/mL compared to the control. Percentage of live sperm with an intact
      acrosome remained similar (P>0.05) in extenders containing different amounts of
      AFGP and control. In conclusion, supplementation of 1 MUg/ml of AFGP in extender
      improved the motility and plasma membrane integrity of Nili-Ravi buffalo sperm
      after thawing.

PMID- 25863988
TI  - Maternal pre-pregnancy BMI, gestational weight gain, and infant birth weight: A
      within-family analysis in the United States.
AB  - In the United States, the high prevalence of unhealthy preconception body weight
      and inappropriate gestational weight gain among pregnant women is an important
      public health concern. However, the relationship among pre-pregnancy BMI,
      gestational weight gain, and newborn birth weight has not been well established.
      This study uses a very large dataset of sibling births and a within-family design
      to thoroughly address this issue. The baseline analysis controlling for mother
      fixed effects indicates maternal preconception overweight, preconception obesity,
      and excessive gestational weight gain significantly increase the risk of having a
      high birth weight baby, respectively, by 1.3, 3 and 3.9 percentage points, while
      underweight before pregnancy and inadequate gestational weight gain increase the
      low birth weight incidence by 1.4 and 2 percentage points. The benchmark results
      are robust in a variety of sensitivity checks. Since poor birth outcomes
      especially high birth weight and low birth weight have lasting adverse impacts on
      one's health, education, and socio-economic outcomes later in life, the findings
      of this research suggest promoting healthy weight among women before pregnancy
      and preventing inappropriate weight gain during pregnancy can generate
      significant intergenerational benefits. 

PMID- 25863989
TI  - Thoracoscopic plication for idiopathic eventration of the bilateral diaphragm:
      Report of a case.
AB  - INTRODUCTION: Diaphragmatic eventration, defined as permanent elevation of the
      diaphragm without defects, is a rare anomaly in adults. Trauma, neoplasms,
      infection, and degenerative disease are the most common causes of this condition,
      whereas idiopathic eventration of the diaphragm is relatively infrequent.
      PRESENTATION OF CASE: We herein present the rare case of an 85-year-old female
      with idiopathic eventration of the bilateral diaphragm. The patient demonstrated
      a rapidly progressive course with dyspnea; therefore, thoracoscopic surgery of
      the unilateral diaphragm was performed. She subsequently withdrew from home
      oxygen therapy, which had introduced preoperatively, and exhibited a significant
      improvement in her pulmonary function for one year after the operation.
      DISCUSSION: Various approaches for diaphragmatic plication have been reported,
      including open (transthoracic or transabdominal) and minimally invasive methods,
      such as thoracoscopic or laparoscopic plication. We consider thoracoscopic
      plication to be an effective minimally invasive method, although single-lung
      ventilation is required. CONCLUSION: We experienced a case in which thoracoscopic
      plication of the unilateral diaphragm resulted in adequate objective improvements
      in the pulmonary function in a patient with idiopathic eventration of the
      bilateral diaphragm.

PMID- 25863990
TI  - Nephroureterectomy for emphysematous pyelonephritis: An aggressive approach is
      sometimes necessary. A case report and literature review.
AB  - INTRODUCTION: Emphysematous pyelonephritis (EPN) is a life-threatening urological
      emergency. A high index of suspicion is required for diagnosis as such patients
      may present to physicians with typical features of pyelonephritis. PRESENTATION
      OF CASE: A 67 year old lady presented atypically to the Emergency Department with
      symptoms of renal colic. The diagnosis of emphysematous pyelonephritis was
      established on prompt CT scanning. She did not respond to conservative
      management. Due to acute, critical deterioration, she underwent a radical right
      nephroureterectomy. The resected kidney involved a long segment of necrotic,
      gangrenous ureter. The patient had a smooth post-operative recovery and was
      successfully discharged. She remains well on follow-up after one year.
      DISCUSSION: Early radiological diagnosis is imperative for risk stratification of
      EPN. Current evidence recommends percutaneous catheter drainage with interval
      nephrectomy as the gold standard treatment. We review the literature for
      pathophysiology and clinical prognostic factors. This case adds onto the limited
      evidence base on ureteric involvement in EPN, suggesting a revision of EPN
      classification. CONCLUSION: Further research on ureteric involvement and
      treatment outcomes in EPN is required. Even in the current era of minimally
      invasive surgery and renal preservation therapies, early open nephrectomy still
      has a role in the management of EPN.

PMID- 25863991
TI  - Extensive preoperative workup in diffuse esophageal leiomyomatosis associated
      with Alport syndrome influences surgical treatment: A case report.
AB  - INTRODUCTION: Diffuse esophageal leiomyomatosis is a rare disease. Misdiagnosis
      is frequent and previous surgeries can complicate surgical management. The only
      treatment described for severe symptomatic cases is esophagectomy. PRESENTATION
      OF CASE: We describe a case of diffuse esophageal leiomyomatosis associated with
      Alport syndrome in a 21 year-old female where endoscopic ultrasonography (EUS)
      with concomitant fluoroscopy and 3D-gastric computed tomography (3D-GCT) modified
      surgical management. DISCUSSION: The diagnosis of diffuse esophageal
      leiomyomatosis is difficult but can be greatly facilitated by extensive
      endoscopic and radiologic workup. Esophagectomy should only be entertained after
      complete anatomic mapping of the lesions, especially after previous surgeries.
      CONCLUSION: EUS and 3D-GCT should strongly be considered as part of routine
      preoperative workup in these patients.

PMID- 25863992
TI  - Giant fibrokeratoma, a rare soft tissue tumor presenting like an accessory digit,
      a case report and review of literature.
AB  - INTRODUCTION: Acquired digital fibrokeratoma is an uncommon, benign fibrous
      tumour that usually occurs in adults as a solitary lesion with a typical size of
      less than 1cm. CASE PRESENTATION: A 48-year-old Afro-Caribbean man presented to
      our foot and ankle clinic with a long-standing growth over the plantar aspect of
      the distal phalanx of the left great toe. The growth was painful and affected the
      patient's mobility. It had gradually increased in size over a period of 17 years.
      The growth was completely excised, and the base was allowed to heal by secondary
      intention. The skin eventually healed, and the patient had a good outcome. The
      histological results confirmed that the growth was a digital fibrokeratoma.
      CONCLUSION: This case is of interest because of the rarity of digital
      fibrokeratoma and the unique morphological appearance of the tumor in this case.
      Additionally, we emphasise the importance of ruling out other causes of abnormal
      growths and considering fibrokeratoma during differential diagnoses.

PMID- 25863993
TI  - Liver hilar tuberculous lymphadenitis successfully diagnosed by laparoscopic
      lymph node biopsy.
AB  - INTRODUCTION: Liver hilar tuberculous lymphadenitis is extremely rare. A case of
      liver hilar tuberculous lymphadenitis mimicking lymph node metastasis of anal
      canal cancer that was successfully diagnosed by laparoscopic lymph node biopsy is
      reported. PRESENTATION OF CASE: A 49-year-old man with a past medical history of
      pulmonary tuberculosis suffering from anal canal cancer with left inguinal lymph
      node metastasis underwent laparoscopic anterior perineal resection and left
      inguinal lymph node dissection in February 2010. Subsequently, he underwent
      dissection of right inguinal lymph node metastases from anal canal cancer twice
      in February and October 2013. In July 2014, follow-up computed tomography (CT)
      showed a 26mm*23mm lesion with calcification on the anterior side of the portal
      vein in the hepatoduodenal ligament. He had no jaundice. Positron emission
      tomography with 2[18 F]-fluoro-2-deoxy-d-glucose (FDG-PET) revealed a mass with
      high uptake. Suspecting a lymph node metastasis from anal canal cancer,
      laparoscopic lymph node biopsy was performed. Histopathological and polymerase
      chain reaction (PCR) examinations yielded a diagnosis of tuberculous
      lymphadenitis. No evidence of recurrence of cancer has been seen during the 5
      years of follow-up after the surgery for anal canal cancer. DISCUSSION: FDG-PET
      imaging is rarely useful for differentiating cancer from tuberculosis lesions.
      Laparoscopic lymph node biopsy is a safe, effective alternative to open surgical
      biopsy. CONCLUSION: Tuberculous lymphadenitis should be included among the
      differential diagnoses of liver hilar lymphadenopathy in patients with a history
      of tuberculous. Laparoscopic lymph node biopsy is useful for the diagnosis of
      undiagnosed lymphadenopathy.

PMID- 25863994
TI  - Angioleiomyoma of urethra: A case report.
AB  - INTRODUCTION: Angioleiomyomas are benign smooth muscle tumors that arise from
      blood vessel walls and commonly involve the deep dermal and subcutaneous tissue.
      Urethral angioleiomyomas are only rarely seen with only less than 5 cases
      reported in literature. PRESENTATION OF CASE: We herein present a case of a 72
      year old man who presented with gross hematuria. Cystoscopy showed a polypoid
      urethral lesion that was resected and on pathologic examination was diagnosed as
      angioleiomyoma. DISCUSSION: Differential diagnoses of a urethral polypoid lesion,
      including inflammatory and neoplastic conditions are discussed. The main emphasis
      is on recognition and review of angioleiomyoma features when presenting in
      commonly encountered locations and other sites that are only rarely involved.
      CONCLUSION: This rare case reports an elderly patient with angioleiomyoma in an
      extremely unusually encountered location and presenting with unusual symptoms of
      gross hematuria that did not recur after resection of the lesion.

PMID- 25863995
TI  - Subscapularis muscle flap for reconstruction of posterior chest wall skeletal
      defect.
AB  - INTRODUCTION: Chest wall skeletal defects are usually closed using muscle flaps
      or prosthetic materials. Postoperative prosthetic infections are critical
      complications and often require plastic surgery support. We report a new surgical
      technique, involving a subscapular muscle flap, for covering posterior chest wall
      defect. PRESENTATION OF CASE: A 75-year-old man was admitted to our hospital. We
      performed a right upper lobectomy with posterior chest wall resection between the
      third and sixth ribs. The resulting chest wall defect was covered with a
      polytetrafluoroethylene mesh that became infected postoperatively. We removed the
      infected mesh and used the subscapularis muscle, the nearest muscle to the
      defect, to cover the chest wall defect. The scapular tip was lifted and the lower
      half of the muscle was dissected. The free end of the flap was sutured to the
      stumps of the anterior serratus and rhomboid major muscles. Computed tomography,
      1 month later, revealed that the flap was engrafted to the chest wall.
      DISCUSSION: No previous study has reported the use of a subscapularis muscle flap
      for chest wall reconstruction. The lower third of the scapula was excised since
      blood supply to the scapula tip may be reduced after dissection of the
      subscapularis muscle, and to prevent the scapula tip from falling into the
      thoracic cavity. CONCLUSION: The use of a subscapularis muscle flap to repair
      chest wall defect is a simple and safe technique that can be conducted in the
      same surgical field as the initial reconstruction surgery and does not require
      plastic surgery support.

PMID- 25863996
TI  - Intraventricular migration of silicone oil: A mimic of traumatic and neoplastic
      pathology.
AB  - We describe an 80-year-old woman with intraventricular silicone oil mimicking
      traumatic pathology upon presentation to the emergency department after a ground
      level fall. Intraventricular migration of silicone oil from prior intraocular
      endotamponade is rare having only been described in a handful of case reports.
      While it has a unique and characteristic appearance on imaging, intraventricular
      silicone oil can be confused with intraventricular hemorrhage or calcified
      ventricular neoplasms. Recognition and differentiation of intraventricular
      silicone oil from more sinister pathology is essential for the radiologist,
      neurologist and neurosurgeon and can be done with routine head CT scan. We
      discuss the imaging findings of intraventricular silicone oil and review the
      current understanding of this unusual phenomenon. 

PMID- 25863997
TI  - Novel use of a double lumen balloon catheter for venous sinus thrombolysis and
      venoplasty.
AB  - We describe the novel use of a double lumen balloon catheter for venous sinus
      thrombolysis and venoplasty. Cerebral venous sinus thrombosis is a rare disease
      that is usually treated with medical anticoagulation. In certain refractory
      cases, surgical or endovascular thrombolysis and thrombectomy may be required. A
      48 year-old man on anticoagulation for cerebral venous sinus thrombosis presented
      with nausea, vomiting and worsening hemiparesis. The patient underwent
      endovascular venous sinus thrombolysis and venoplasty with continuous in situ
      tissue plasminogen activator (tPA) infusion over 48 hours. This novel approach to
      the endovascular treatment of venous sinus thrombosis, including the use of a
      double lumen balloon was advantageous, as it allowed direct infusion of tPA
      through the balloon catheter without having to exchange the balloon for a
      microcatheter.

PMID- 25863998
TI  - Hypertrophic olivary degeneration secondary to pontine haemorrhage.
AB  - We report a 58-year-old man who developed hyptertrophic olivary degeneration
      (HOD) after haemorrhage of a cavernous malformation in the pons. Lesions of the
      triangle of Guillain and Mollaret (the dentatorubro-olivary pathway) may lead to
      HOD, a secondary transsynaptic degeneration of the inferior olivary nucleus. HOD
      is considered unique because the degenerating olive initially becomes
      hypertrophic rather than atrophic. The primary lesion causing pathway
      interruption is often haemorrhage, either due to hypertension, trauma, surgery
      or, as in our patient, a vascular malformation such as a cavernoma. Ischaemia and
      demyelination can also occasionally be the inciting events. The classic clinical
      presentation of HOD is palatal myoclonus, although not all patients with HOD
      develop this symptom. The imaging features of HOD evolve through characteristic
      phases. The clue to the diagnosis of HOD is recognition of the distinct imaging
      stages and identification of a remote primary lesion in the triangle of Guillain
      and Mollaret. Familiarity with the classic imaging findings of this rare
      phenomenon is necessary in order to avoid misdiagnosis and prevent unnecessary
      intervention. 

PMID- 25863999
TI  - Medial cortex fracture patterns after sagittal split osteotomy using short versus
      long medial cuts: can we obviate bad splits?
AB  - The aim of the present study was to evaluate the lingual fracture patterns after
      sagittal split osteotomy (SSO) using short and long medial osteotomy cuts, via
      three-dimensional (3D) cone beam computed tomography (CBCT). Forty-six subjects
      participated in this prospective study. Two types of medial osteotomy line were
      made: for type I, the medial osteotomy line was finished just before the lingula;
      for type II, the medial osteotomy line was extended 3-4mm beyond the lingula.
      Three fracture patterns were observed after SSOs. There were no significant
      differences in the medial fracture patterns between the two medial osteotomy
      types (P=0.16). The buccolingual thickness of the ramus was lower in fractures
      with pattern 3 (bad split) than in the two other fracture patterns. The length of
      the medial osteotomy line - short or long - did not alter the prevalence of a bad
      split. The bone thickness of the ramus may affect the type of fracture pattern on
      the medial side of the ramus. 

PMID- 25864000
TI  - Changes in occlusal function after orthognathic surgery in mandibular prognathism
      with and without asymmetry.
AB  - This study aimed to evaluate the postoperative changes in masticatory function in
      patients with jaw deformities with or without asymmetry treated by orthognathic
      surgery. Thirty female patients who underwent a Le Fort I osteotomy with sagittal
      split ramus osteotomy (SSRO) were enrolled. The patients were divided into
      symmetry and asymmetry groups. The bite force, occlusal contact area, and bite
      force balance were measured before and at 1, 3, and 6 months and 1 year after
      surgery; these measurements were compared statistically within and between the
      two groups. In the symmetry group, there was a significant difference in the
      preoperative bite force and the 1 month postoperative bite force (P=0.0033). In
      the asymmetry group, the bite force before surgery was significantly different
      from that at 1 month (P=0.0375) and at 1 year (P=0.0353) after surgery.
      Significant differences in the bite force were also observed between the
      following time points: 1 month and 1 year (P=0.0003), 3 months and 1 year
      (P=0.0034), and 1 month and 6 months (P=0.0486). The occlusal contact area, bite
      force, and occlusal balance tended to change after Le Fort I osteotomy with SSRO,
      with a significantly improved bite force in patients with asymmetry before
      surgery. 

PMID- 25864001
TI  - A rare case of Ramsay Hunt syndrome following temporomandibular joint surgery.
AB  - Surgical approaches to the temporomandibular joint (TMJ) have been designed
      specifically to minimize injury to the temporal branch of the facial nerve. In
      spite of this, facial nerve dysfunction occurs in 1-32% of patients undergoing
      TMJ surgery. Ramsay Hunt syndrome is characterized by peripheral facial paralysis
      that often involves other cranial nerves, mostly cranial nerve VIII. The
      pathology is attributed to the reactivation of latent varicella zoster virus in
      the geniculate ganglion. The diagnosis is based mostly on history and physical
      findings. Surgical procedures have been known to reactivate varicella zoster
      virus, but Ramsay Hunt syndrome subsequent to TMJ surgery has not been described
      yet. This report describes a case of Ramsay Hunt syndrome associated with TMJ
      surgery. Because of the relatively high incidence of facial nerve dysfunction
      associated with TMJ surgery, patients with varicella zoster virus reactivation
      may initially be misdiagnosed with iatrogenic facial palsy, or vice versa. 

PMID- 25864002
TI  - Applying a statewide geospatial leaching tool for assessing soil vulnerability
      ratings for agrochemicals across the contiguous United States.
AB  - A large-scale leaching assessment tool not only illustrates soil (or groundwater)
      vulnerability in unmonitored areas, but also can identify areas of potential
      concern for agrochemical contamination. This study describes the methodology of
      how the statewide leaching tool in Hawaii modified recently for use with
      pesticides and volatile organic compounds can be extended to the national
      assessment of soil vulnerability ratings. For this study, the tool was updated by
      extending the soil and recharge maps to cover the lower 48 states in the United
      States (US). In addition, digital maps of annual pesticide use (at a national
      scale) as well as detailed soil properties and monthly recharge rates (at high
      spatial and temporal resolutions) were used to examine variations in the leaching
      (loads) of pesticides for the upper soil horizons. Results showed that the
      extended tool successfully delineated areas of high to low vulnerability to
      selected pesticides. The leaching potential was high for picloram, medium for
      simazine, and low to negligible for 2,4-D and glyphosate. The mass loadings of
      picloram moving below 0.5 m depth increased greatly in northwestern and central
      US that recorded its extensive use in agricultural crops. However, in addition to
      the amount of pesticide used, annual leaching load of atrazine was also affected
      by other factors that determined the intrinsic aquifer vulnerability such as soil
      and recharge properties. Spatial and temporal resolutions of digital maps had a
      great effect on the leaching potential of pesticides, requiring a trade-off
      between data availability and accuracy. Potential applications of this tool
      include the rapid, large-scale vulnerability assessments for emerging
      contaminants which are hard to quantify directly through vadose zone models due
      to lack of full environmental data.

PMID- 25864003
TI  - Spatial distribution of Legionella pneumophila MLVA-genotypes in a drinking water
      system.
AB  - Bacteria of the genus Legionella cause water-based infections, resulting in
      severe pneumonia. To improve our knowledge about Legionella spp. ecology, its
      prevalence and its relationships with environmental factors were studied.
      Seasonal samples were taken from both water and biofilm at seven sampling points
      of a small drinking water distribution system in Israel. Representative isolates
      were obtained from each sample and identified to the species level. Legionella
      pneumophila was further determined to the serotype and genotype level. High
      resolution genotyping of L. pneumophila isolates was achieved by Multiple-Locus
      Variable number of tandem repeat Analysis (MLVA). Within the studied water
      system, Legionella plate counts were higher in summer and highly variable even
      between adjacent sampling points. Legionella was present in six out of the seven
      selected sampling points, with counts ranging from 1.0 * 10(1) to 5.8 * 10(3)
      cfu/l. Water counts were significantly higher in points where Legionella was
      present in biofilms. The main fraction of the isolated Legionella was L.
      pneumophila serogroup 1. Serogroup 3 and Legionella sainthelensis were also
      isolated. Legionella counts were positively correlated with heterotrophic plate
      counts at 37  degrees C and negatively correlated with chlorine. Five MLVA
      genotypes of L. pneumophila were identified at different buildings of the sampled
      area. The presence of a specific genotype, "MLVA-genotype 4", consistently co
      occurred with high Legionella counts and seemed to "trigger" high Legionella
      counts in cold water. Our hypothesis is that both the presence of L. pneumophila
      in biofilm and the presence of specific genotypes, may indicate and/or even lead
      to high Legionella concentration in water. This observation deserves further
      studies in a broad range of drinking water systems to assess its potential for
      general use in drinking water monitoring and management.

PMID- 25864004
TI  - Mathematical model of a parallel plate ammonia electrolyzer for combined
      wastewater remediation and hydrogen production.
AB  - A mathematical model was developed for the simulation of a parallel plate ammonia
      electrolyzer to convert ammonia in wastewater to nitrogen and hydrogen under
      basic conditions. The model consists of fundamental transport equations, the
      ammonia oxidation kinetics at the anode, and the hydrogen evolution kinetics at
      the cathode of the electrochemical reactor. The model shows both qualitative and
      quantitative agreement with experimental measurements at ammonia concentrations
      found within wastewater (200-1200 mg L(-1)). The optimum electrolyzer performance
      is dependent on both the applied voltage and the inlet concentrations. Maximum
      conversion of ammonia to nitrogen at the rates of 0.569 and 0.766 mg L(-1) min(
      1) are achieved at low (0.01 M NH4Cl and 0.1 M KOH) and high (0.07 M NH4Cl and
      0.15 M KOH) inlet concentrations, respectively. At high and low concentrations,
      an initial increase in the cell voltage will cause an increase in the system
      response - current density generated and ammonia converted. These system
      responses will approach a peak value before they start to decrease due to surface
      blockage and/or depletion of solvated species at the electrode surface.
      Furthermore, the model predicts that by increasing the reactant and electrolyte
      concentrations at a certain voltage, the peak current density will plateau,
      showing an asymptotic response.

PMID- 25864006
TI  - Critical insights for a sustainability framework to address integrated community
      water services: Technical metrics and approaches.
AB  - Planning for sustainable community water systems requires a comprehensive
      understanding and assessment of the integrated source-drinking-wastewater systems
      over their life-cycles. Although traditional life cycle assessment and similar
      tools (e.g. footprints and emergy) have been applied to elements of these water
      services (i.e. water resources, drinking water, stormwater or wastewater
      treatment alone), we argue for the importance of developing and combining the
      system-based tools and metrics in order to holistically evaluate the complete
      water service system based on the concept of integrated resource management. We
      analyzed the strengths and weaknesses of key system-based tools and metrics, and
      discuss future directions to identify more sustainable municipal water services.
      Such efforts may include the need for novel metrics that address system
      adaptability to future changes and infrastructure robustness. Caution is also
      necessary when coupling fundamentally different tools so to avoid
      misunderstanding and consequently misleading decision-making. 

PMID- 25864005
TI  - Occurrence and removal of progestagens in two representative swine farms:
      Effectiveness of lagoon and digester treatment.
AB  - A total of 21 progestagens were screened in animal wastes and environmental
      samples from two representative swine farms and surrounding environments of South
      China using ultra-high-performance liquid chromatography tandem mass spectrometry
      (UHPLC-MS/MS) to assess the effectiveness of simple lagoon (and digester)
      treatment. The results showed that 11, 8 and 8 of 21 target progestagens were
      detected with the minimum concentration of 2.31 ng/L and maximum of 6150 ng/L in
      the water samples, with the minimum of 1.36 ng/L and maximum of 98.3 ng/L in the
      suspended particles, and with the minimum of 1.57 ng/g dry weight (dw) and
      maximum of 3310 ng/g dw in the solid samples, respectively. Trace levels (a few
      ng/L or ng/g levels) of dydrogesterone, 5alpha-dihydroprogesterone, norgestrel
      and progesterone were found in samples from nearby surface waters and vegetable
      fields impacted by animal wastes. The residual progestagens at the reported
      levels may still pose potential risks to aquatic organisms such as fish in the
      receiving aquatic environments. This finding suggests that swine wastewater and
      feces could lead to contamination of some detectable progestagens in the
      surrounding environments. Significant reduction in total progestagen
      concentrations were observed from the fresh swine wastewaters to the fish ponds,
      indicating effective removal of these compounds by the lagoon (and digester)
      treatment. In addition, the biogas digesters provided high removal of the
      progestagens in the waste streams. This low-cost and eco-friendly treatment
      system should be promoted in developing countries with concentrated animal
      operations.

PMID- 25864007
TI  - Selective extraction of histidine derivatives by metal affinity with a copper(II)
      chelating ligand complex in an aqueous two-phase system.
AB  - Affinity extraction based on the interaction between a target molecule and a
      specific affinity ligand offers a novel separation system for biomolecules in an
      aqueous two-phase system, however, most of affinity ligands are expensive. In the
      present study, metal affinity extraction of histidine (His) derivatives using a
      complex between Cu(II) and a commercially available chelating ligand was studied
      in a poly(ethylene glycol) (PEG)/Li2SO4 ATPS. Alizarin complexone (3-[N,N
      bis(carboxymethyl)amino methyl]-1,2-dihydroxy anthraquinone, AC) was selected as
      the chelating ligand because of the good extractability of Cu(II) into the upper
      PEG-rich phase. On the basis of coordinate bonding with Cu(II), the extraction of
      His in the presence of the Cu(II)-AC complex under neutral condition was 73%,
      which was much higher than that under Cu(II) free condition (13%). Among a series
      of divalent transition metal ions (Cu(II), Ni(II), Co(II), and Zn(II)), Cu(II)
      was the most effective for the extraction of His. Derivatives of His were
      selectively extracted in the presence of many other amino acids because of the
      specificity of the interaction between Cu(II) and imidazole group of His.
      Extracted His was quantitatively stripped from the Cu(II)-AC complex using
      competitive complexation with agents such as iminodiacetic acid and imidazole. 

PMID- 25864008
TI  - A validated LC-MS/MS method for determination of periplogenin in rat plasma and
      its application in pharmacokinetic study.
AB  - A method coupling high performance liquid chromatography with tandem mass
      spectrometry has been developed and validated for quantifying periplogenin in rat
      plasma using psoralen as an internal standard (IS). Plasma samples were
      pretreated using a simple liquid-liquid extraction with ethyl acetate and the
      chromatographic separation of periplogenin and psoralen was achieved on a Waters
      XBridgeTM BEH C18 column with 0.1% formic acid and acetonitrile as mobile phase
      at a flow rate of 0.4mL/min. The detection was performed on a positive ion mode
      with electrospray ionization (ESI) source. The optimized ion transition pairs for
      quantitation were m/z 391.3->m/z 337.2 for periplogenin and m/z 187.0->m/z 131.0
      for IS. The total run time was 9.0min. The calibration curve was linear over the
      range of 0.2-250ng/mL (r>0.99) with the lower limit of quantitation (LLOQ) at
      0.2ng/mL. The intra- and inter-day precision were below 9.85% and the mean
      accuracy were from -10.03% to 10.26%. The average recoveries of periplogenin in
      plasma ranged from 85.1% to 95.6%. The proposed method was successfully applied
      in evaluating the pharmacokinetics of periplogenin after an oral dose of 30mg/kg
      Cortex Periplocae extract in rats. 

PMID- 25864009
TI  - Fibrous polymer grafted magnetic chitosan beads with strong poly(cation-exchange)
      groups for single step purification of lysozyme.
AB  - Lysozyme is an important polypetide used in medical and food applications. We
      report a novel magnetic strong cation exchange beads for efficient purification
      of lysozyme from chicken egg white. Magnetic chitosan (MCHT) beads were
      synthesized via phase inversion method, and then grafted with poly(glycidyl
      methacrylate) (p(GMA)) via the surface-initiated atom transfer radical
      polymerization (SI-ATRP). Epoxy groups of the grafted polymer, were modified into
      strong cation-exchange groups (i.e., sulfonate groups) in the presence of sodium
      sulfite. The MCTH and MCTH-g-p(GMA)-SO3H beads were characterized by ATR-FTIR,
      SEM, and VSM. The sulphonate groups content of the modified MCTH-g-p(GMA)-4 beads
      was found to be 0.53mmolg(-1) of beads by the potentiometric titration method.
      The MCTH-g-p(GMA)-SO3H beads were first used as an ion-exchange support for
      adsorption of lysozyme from aqueous solution. The influence of different
      experimental parameters such as pH, contact time, and temperature on the
      adsorption process was evaluated. The maximum adsorption capacity was found to be
      208.7mgg(-1) beads. Adsorption of lysozyme on the MCTH-g-p(GMA)-SO3H beads fitted
      to Langmuir isotherm model and followed the pseudo second-order kinetic. More
      than 93% of the adsorbed lysozyme was desorbed using Na2CO3 solution (pH 11.0).
      The purity of the lysozyme was checked by HPLC and SDS gel electrophoresis. In
      addition, the MCTH-g-p(GMA)-SO3H beads prepared in this work showed promising
      potential for separation of various anionic molecules. 

PMID- 25864010
TI  - Fabrication of a polystyrene microfluidic chip coupled to electrospray ionization
      mass spectrometry for protein analysis.
AB  - A highly integrated polystyrene (PS) microfluidic chip coupled to electrospray
      ionization mass spectrometry for on-chip protein digestion and online analysis
      was developed. The immobilized enzymatic microreactor for on-chip protein
      digestion was integrated onto microchip via the novel method of region-selective
      UV-modification combined with glutaraldehyde-based immobilization. The micro film
      electric contact for applying high voltage was prepared on chips by using UV
      directed electroless plating technique. A micro-tip was machined at the end of
      main channel, serving as the interface between microchip and mass spectrometric
      detector. On-chip digestion and online detection of protein was carried out by
      coupling the microchip with mass spectrometry (MS). The influences of methanol
      flow rate in side channel on the stability of spray and intensity of signals were
      investigated systematically. Also the influence of sample flow rate on the
      performance of immobilized enzymatic reactor were investigated. Stable spray was
      obtained at the spray voltage of 2.8-3.0kV and the methanol flow rate of 500
      700nLmin(-1) with the relative standard deviation (RSD) of total ion current
      (TIC) less than 10%. The influence of sample flow rate on the performance of
      immobilized enzymatic reactor was also studied. The sequence coverage of protein
      identification decreased with the increase of flow rate of the sample solution. A
      sequence coverage of 96% was obtained with immobilized enzymatic reactor at the
      sample flow rate of 100nLmin(-1) with the reaction time of 8.4min. It could
      detect cytochrome c as low as 10MUgmL(-1) with the developed system. No obvious
      decrease in protein digestion efficiency was observed after the chip continuously
      performed for 4h and stored for 15d. 

PMID- 25864011
TI  - Isolation of C-glycosylflavonoids with alpha-glucosidase inhibitory activity from
      Passiflora bogotensis Benth by gradient high-speed counter-current
      chromatography.
AB  - In this study, we applied a gradient High-Speed Counter-Current Chromatography
      (HSCCC) method that allowed, by direct injection of an aqueous crude extract of
      the leaves of Passiflora bogotensis, the successful isolation of six flavonoids
      in a single run, with purity of each compound higher than 81%. This separation
      enabled the isolation of two new flavonoid glycosides, apigenin-6-C-alpha-l
      rhamnopyranosyl-(1->2)-(6"-O-acetyl)-beta-d-glucopyranoside (2) and luteolin-6-C
      alpha-l-rhamnopyranosyl-(1->2)-(6"-O-acetyl)-beta-d-glucopyranoside (4), and four
      known ones, isovitexin (1), isoorientin (3), isovitexin-2"-O-rhamnoside (5) and
      isoorientin-2"-O-rhamnoside (6). The structures of the isolated compounds were
      identified by HPLC-DAD, LC-MS, (1)H and (13)C NMR and comparison with literature
      data. The inhibitory activities of all of these compounds were evaluated in vitro
      on alpha-glucosidase from S. cerevisiae, and the IC50 was determinate. This is
      the first study concerning the chemical composition and biological activity of
      Passiflora bogotensis. 

PMID- 25864012
TI  - Preparative isolation and purification of urolithins from the intestinal
      metabolites of pomegranate ellagitannins by high-speed counter-current
      chromatography.
AB  - Urolithins were separated from the intestinal metabolites of pomegranate
      ellagitannins by high-speed counter current chromatography in two steps using two
      solvent systems composed of n-hexane-ethyl acetate-methanol-acetic acid-water
      (2.5:2:0.25:5, v/v/v/v/v) and n-hexane-ethyl acetate-methanol-acetic acid-water
      (2.5:0. 8:0.25:5, v/v/v/v/v) for the first time. Each injection of 100mg extract
      yielded 21mg of pure urolithin A and 10mg of pure urolithin B. High-performance
      liquid chromatography analyses revealed that the purity of urolithin A and
      urolihtin B was over 98.5%. The structures of urolithin A and urolitihn B were
      identified by high resolution-MS, NMR and single crystal x-ray analysis.
      Urolithins reduced the oxidative stress status in colon cancer by decreasing the
      intracellular ROS and malondialdehyde levels, and increasing SOD activity in H2O2
      treated Caco-2 cells. 

PMID- 25864013
TI  - Determination of N-methylcytisine in rat plasma by UPLC-MS/MS and its application
      to pharmacokinetic study.
AB  - In this work, a sensitive and selective UPLC-MS/MS method for determination of N
      methylcytisine in rat plasma is developed. After addition of hordenine as an
      internal standard (IS), protein precipitation by acetonitrile-methanol (9:1, v/v)
      was used to prepare samples. Chromatographic separation was achieved on a UPLC
      BEH HILIC (2.1 mm*100mm, 1.7MUm) with acetonitrile (containing 10mM ammonium
      formate) and water (containing 0.1% formic acid and 10mM ammonium formate) as the
      mobile phase with gradient elution. An electrospray ionization source was applied
      and operated in positive ion mode; multiple reaction monitoring (MRM) mode was
      used for quantification using target fragment ions m/z 205.1->58.0 for N
      methylcytisine, and m/z 166.1->121.0 for IS. Calibration plots were linear
      throughout the range 2-2000ng/mL for N-methylcytisine in rat plasma. Mean
      recoveries of N-methylcytisine in rat plasma ranged from 86.1% to 94.8%. RSD of
      intra-day and inter-day precision were both<13%. The accuracy of the method was
      between 94.5% and 109.4%. The method was successfully applied to pharmacokinetic
      study of N-methylcytisine after either oral or intravenous administration. For
      the first time, the absolute bioavailability of N-methylcytisine was reported as
      high as 55.5%. 

PMID- 25864014
TI  - Simultaneous determination of andrographolide, dehydroandrographolide and
      neoandrographolide in dog plasma by LC-MS/MS and its application to a dog
      pharmacokinetic study of Andrographis paniculata tablet.
AB  - In this study, a sensitive and rapid liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) method was developed and validated to simultaneously
      determinate andrographolide (AP), dehydroandrographolide (DP), and
      neoandrographolide (NP) in plasma of beagle dogs after oral administration of
      Andrographis paniculata tablet (A. paniculata). The analytes and bilobalide
      (internal standard) were separated on an Agilent ZORBAX XDB-C18 column
      (50mm*2.1mm, 3.5MUm) by using gradient elution consisting of methanol and water
      at a flow rate of 0.50mL/min in 7min. Multiple reaction monitoring (MRM) mode was
      performed to quantify data under monitoring precursor-product ion transitions of
      m/z 348.8->286.9, 330.9->107.9, 479.1->160.8 and 325.0->163.0 for AP, DP, NP and
      internal standard (IS) at negative ion mode, respectively. This method was
      developed at linearity ranging from 0.50 to 250ng/mL for AP, 1.00 to 500ng/mL for
      DP and 0.20 to 100ng/mL for NP. The accuracy of each analyte ranged between 94.8%
      and 107.1% and the precision was within 14.6%. No significant matrix effect was
      observed. AP, DP and NP were stable during sample storage, preparation and
      analytic procedures. Furthermore, this method was successfully applied in the
      investigation of the pharmacokinetic profile of AP, DP and NP in beagle dogs
      after oral administration of A. paniculata tablet (49.5mg for AP, 7.0mg for DP,
      22.0mg for NP). Biological half-life (t1/2) was 2.08+/-0.99, 3.13+/-1.19 and
      1.07+/-0.38h for AP, DP and NP, respectively. The areas under curves (AUC0-t) of
      AP, DP and NP was 494.50+/-150.64, 26.01+/-8.72 and 78.78+/-18.29ngh/mL,
      respectively. 

PMID- 25864015
TI  - Determination of neonicotinoid insecticides and their metabolites in honey bee
      and honey by liquid chromatography tandem mass spectrometry.
AB  - The original analytical method for the simultaneous determination and
      confirmation of neonicotinoids insecticides (imidacloprid, clothianidin,
      acetamiprid, thiametoxam, thiacloprid, nitenpyram, dinotefuran) and some of their
      metabolites (imidacloprid guanidine, imidacloprid olefin, imidacloprid urea,
      desnitro-imidacloprid hydrochloride, thiacloprid-amid and acetamiprid-N
      desmethyl) in honey bee and honey was developed. Preparation of honey bee samples
      involves the extraction with mixture of acetonitrile and ethyl acetate followed
      by cleaned up using the Sep-Pak Alumina N Plus Long cartridges. Honey samples
      were dissolved in 1% mixture of acetonitrile and ethyl acetate with addition of
      TEA, then extracts were cleaned up with Strata X-CW cartridges. The identity of
      analytes was confirmed using liquid chromatography tandem mass spectrometry. All
      compounds were separated on a Luna C18 column with gradient elution. The whole
      procedure was validated according to the requirements of SANCO 12571/2013. The
      average recoveries of the analytes ranged from 85.3% to 112.0%, repeatabilities
      were in the range of 2.8-11.2%, within-laboratory reproducibility was in the
      range of 3.3-14.6%, the limits of quantitation were in the range of 0.1-0.5MUgkg(
      1), depending of analyte and matrices. The validated method was successfully
      applied for the determination of clothianidin, imidacloprid and imidacloprid urea
      in real incurred honey bee samples and clothianidin in honey. 

PMID- 25864016
TI  - [Equality in clinical practice. Proposals for patients, professionals and
      managers and policies to limit discrimination].
AB  - OBJECTIVE: To make feasible and practical proposals to improve equality in the
      course of clinical care during the patient-provider encounter. METHODS: Design: A
      focus group study was conducted with a qualitative approach from the perspective
      of reducing health inequalities in the clinic. Setting: A classroom discussion
      focused on equality in clinical work. Subjects: 98 professionals from several
      countries. Measurement tools: An analysis of the responses was performed, grouped
      by themes interpreted by analysts, and restructured to provide consistency and
      uniformity to responses given. Data were collected using a questionnaire with
      open answers, allowing free-form answers to three general questions that
      addressed improving equality from the perspective of the professional themselves,
      patients, and health policy managers. No saturation horizon of analytical
      discourses was set, to understand that from this subjective prioritization of
      opinion there is no possibility that discourses reached saturation. RESULTS:
      Responses were added to the 3 principal axes, recommending that professionals be
      aware of their discriminatory ability. Patients were asked to trust their health
      professionals and that they should be assigned to a professional. It was also
      proposed that managers provide information systems, help reduce health
      inequalities, and encourage professional freedom. CONCLUSIONS: The paper presents
      concrete measures to promote improved equality in clinics during the delivery of
      health care.

PMID- 25864017
TI  - Improved Segmentation of Multiple Cavities of the Heart in Wide-View 3-D
      Transesophageal Echocardiograms.
AB  - Minimally invasive interventions in the heart such as in electrophysiology are
      becoming more and more important in clinical practice. Currently, preoperative
      computed tomography angiography (CTA) is used to provide anatomic information
      during electrophysiology interventions, but this does not provide real-time
      feedback and burdens the patient with additional radiation and side effects of
      the contrast agent. Three-dimensional transesophageal echocardiography (TEE) is
      an excellent modality for visualization of anatomic structures and instruments in
      real time, but some cavities, especially the left atrium, suffer from the limited
      coverage of the 3-D TEE volumes. This leads to difficulty in segmenting the left
      atrium. We propose replacing or complementing pre-operative CTA imaging with wide
      view TEE. We tested this proposal on 20 patients for which TEE image volumes
      covering the left atrium and CTA images were acquired. The TEE images were
      manually registered, and wide-view volumes were generated. Five heart cavities in
      single-view and wide-view TEE were segmented and compared with atlas based
      segmentations derived from the CTA images. We found that the segmentation
      accuracy (Dice coefficients) improved relative to segmentation of single-view
      images by 5, 15 and 9 percentage points for the left atrium, right atrium and
      aorta, respectively. Average anatomic coverage was improved by 2, 29, 62 and 49
      percentage points for the right ventricle, left atrium, right atrium and aorta,
      respectively. This finding confirms that wide-view 3-D TEE can be useful in
      supporting electrophysiology interventions. 

PMID- 25864018
TI  - Development of a New Ultrasound-Based System for Tracking Motion of the Human
      Lumbar Spine: Reliability, Stability and Repeatability during Forward Bending
      Movement Trials.
AB  - The aim of this study was to develop a new method for quantifying intersegmental
      motion of the spine in an instrumented motion segment L4-L5 model using
      ultrasound image post-processing combined with an electromagnetic device. A
      prospective test-retest design was employed, combined with an evaluation of
      stability and within- and between-day intra-tester reliability during forward
      bending by 15 healthy male patients. The accuracy of the measurement system using
      the model was calculated to be +/- 0.9 degrees  (standard deviation = 0.43) over
      a 40 degrees  range and +/- 0.4 cm (standard deviation = 0.28) over 1.5 cm. The
      mean composite range of forward bending was 15.5 +/- 2.04 degrees  during a
      single trial (standard error of the mean = 0.54, coefficient of variation =
      4.18). Reliability (intra-class correlation coefficient = 2.1) was found to be
      excellent for both within-day measures (0.995-0.999) and between-day measures
      (0.996-0.999). Further work is necessary to explore the use of this approach in
      the evaluation of biomechanics, clinical assessments and interventions. 

PMID- 25864019
TI  - Built environment and obesity by urbanicity in the U.S.
AB  - Based on the data from the Behavioral Risk Factor Surveillance System 2012, this
      study examines the association of neighborhood built environments with individual
      physical inactivity and obesity in the U.S. Multilevel modeling is used to
      control for the effects of individual socio-demographic characteristics.
      Neighborhood variables include built environment, poverty level and urbanicity at
      the county level. Among the built environment variables, a poorer street
      connectivity and a more prominent presence of fast-food restaurants are
      associated with a higher obesity risk (especially for areas of certain urbanicity
      levels). Analysis of data subsets divided by areas of different urbanicity levels
      and by gender reveals the variability of effects of independent variables, more
      so for the neighborhood variables than individual variables. This implies that
      some obesity risk factors are geographically specific and vary between men and
      women. The results lend support to the role of built environment in influencing
      people's health behavior and outcome, and promote public policies that need to be
      geographically adaptable and sensitive to the diversity of demographic groups.

PMID- 25864020
TI  - Triage for suspected acute Pulmonary Embolism: Think before opening Pandora's
      Box.
AB  - This is a review of the current strengths and weaknesses of the various imaging
      modalities available for the diagnosis of suspected non-massive Pulmonary
      Embolism (PE). Without careful consideration for the clinical presentation, and
      the timely application of clinical decision support (CDS) methodology, the
      current overutilization of imaging resources for this disease will continue. For
      a patient with a low clinical risk profile and a negative D-dimer there is no
      reason to consider further workup with imaging; as the negative predictive value
      in this scenario is the same as imaging. While the current efficacy and
      effectiveness data support the continued use of Computed Tomographic angiography
      (CTA) as the imaging golden standard for the diagnosis of PE; this test does have
      the unintended consequences of radiation exposure, possible overdiagnosis and
      overuse. There is a persistent lack of appreciation on the part of ordering
      physicians for the effectiveness of the alternatives to CTA (ventilation
      perfusion imaging and contrast enhanced magnetic resonance angiography) in these
      patients. Careful use of standardized protocols for patient triage and the
      application of CDS will allow for a better use of imaging resources. 

PMID- 25864021
TI  - Human Papilloma Virus and Cervical Cancer Education Needs among HIV-Positive
      Haitian Women in Miami.
AB  - BACKGROUND: Haitian immigrant women, the largest growing Black ethnic group in
      Miami, experience the highest rates of cervical cancer and account for one of the
      largest populations diagnosed with human immunodeficiency virus/acquired
      immunodeficiency syndrome (HIV/AIDS) in South Florida. Using community-based
      participatory research methods, we conducted a pilot study to examine human
      papilloma virus (HPV)/cervical cancer knowledge and identify intervention
      preferences among HIV positive Haitian women. METHODS: Community health workers
      conducted three focus groups with 21 HIV-positive Haitian women. All sessions
      were conducted in Haitian Kreyol, digitally recorded, and subsequently
      interpreted and transcribed into English. The first focus group assessed
      HPV/cervical cancer knowledge, the second session explored HPV/cervical cancer
      considerations specific to HIV-positive women, and the third focus group
      discussed HPV/cervical cancer screening and intervention preferences. Data
      analysis was guided by a grounded theory approach. FINDINGS: Our sample had
      limited HPV/cervical cancer knowledge. Misconceptions about screening,
      transmission, and treatment were common. Participants felt that stigma by
      providers impacted negatively the care they received and that stigma by the
      community diminished social support. Strong support for culturally tailored
      interventions to improve HPV/cervical cancer knowledge was expressed. Although no
      participants had participated in research previously, all were willing to
      participate in future trials. CONCLUSIONS: There is critical need for culturally
      relevant interventions to improve HPV/cervical cancer knowledge among HIV
      positive Haitian women.

PMID- 25864022
TI  - Transforming Patient-Centered Care: Development of the Evidence Informed Decision
      Making through Engagement Model.
AB  - BACKGROUND: In response to the passage of the Affordable Care Act in the United
      States, clinicians and researchers are critically evaluating methods to engage
      patients in implementing evidence-based care to improve health outcomes. However,
      most models on implementation only target clinicians or health systems as the
      adopters of evidence. Patients are largely ignored in these models. A new
      implementation model that captures the complex but important role of patients in
      the uptake of evidence may be a critical missing link. DISCUSSION: Through a
      process of theory evaluation and development, we explore patient-centered
      concepts (patient activation and shared decision making) within an implementation
      model by mapping qualitative data from an elective induction of labor study to
      assess the model's ability to capture these key concepts. The process
      demonstrated that a new, patient-centered model for implementation is needed. In
      response, the Evidence Informed Decision Making through Engagement Model is
      presented. We conclude that, by fully integrating women into an implementation
      model, outcomes that are important to both the clinician and patient will
      improve. CONCLUSIONS: In the interest of providing evidence-based care to women
      during pregnancy and childbirth, it is essential that care is patient centered.
      The inclusion of concepts discussed in this article has the potential to extend
      beyond maternity care and influence other clinical areas. Utilizing the newly
      developed Evidence Informed Decision Making through Engagement Model provides a
      framework for utilizing evidence and translating it into practice while
      acknowledging the important role that women have in the process.

PMID- 25864023
TI  - Disparities in receipt of breast and cervical cancer screening for rural women
      age 18 to 64 with disabilities.
AB  - BACKGROUND: Previous research has found breast and cervical cancer screening
      disparities between women with and without disabilities, and between women living
      in rural versus urban areas. Living in a rural area may add to the barriers women
      with disabilities experience when attempting to obtain screening for breast and
      cervical cancer. The purpose of this study was to examine the combination of
      disability status and rurality in association with receipt of breast and cervical
      cancer screening among women age 18 to 64 in the United States. METHODS: We
      conducted cross-sectional analyses of data from the Medical Expenditure Panel
      Survey, using pooled annual data files from 2002 through 2008. We compared recent
      receipt of breast and cervical cancer screening among four groups: 1) urban women
      without disabilities, 2) urban women with disabilities, 3) rural women without
      disabilities, and 4) rural women with disabilities. FINDINGS: Overall, women with
      disabilities were less likely to be up to date with mammograms and Pap tests
      compared with women with no disabilities. Similarly, women in rural areas were
      less likely to have received breast or cervical cancer screening within
      recommended timeframes. Women who both had a disability and lived in a rural area
      were the least likely to be current with screening. CONCLUSIONS: Our findings
      suggest that living in rural regions compounds disparities in receipt of cancer
      screening among women with disabilities. Increased attention is needed to improve
      receipt of cancer screening among rural women with disabilities.

PMID- 25864024
TI  - The landscape of precision cancer medicine clinical trials in the United States.
AB  - PURPOSE: Advances in tumor biology and multiplex genomic analysis have ushered in
      the era of precision cancer medicine. Little is currently known, however, about
      the landscape of prospective "precision cancer medicine" clinical trials in the
      U.S. METHODS: We identified all adult interventional cancer trials registered on
      ClinicalTrials.gov between September 2005 and May 2013. Trials were classified as
      "precision cancer medicine" if a genomic alteration in a predefined set of 88
      genes was required for enrollment. Baseline characteristics were ascertained for
      each trial. RESULTS: Of the initial 18,797 trials identified, 9094 (48%) were
      eligible for inclusion: 684 (8%) were classified as precision cancer medicine
      trials and 8410 (92%) were non-precision cancer medicine trials. Compared with
      non-precision cancer medicine trials, precision cancer medicine trials were
      significantly more likely to be phase II [RR 1.19 (1.10-1.29), p<0.001], multi
      center [RR 1.18 (1.11-1.26), p<0.001], open-label [RR 1.04 (1.02-1.07), p=0.005]
      and involve breast [RR 4.03 (3.49-4.52), p<0.001], colorectal [RR 1.62 (1.22
      2.14), p=0.002] and skin [RR 1.98 (1.55-2.54), p<0.001] cancers. Precision
      medicine trials required 38 unique genomic alterations for enrollment. The
      proportion of precision cancer medicine trials compared to the total number of
      trials increased from 3% in 2006 to 16% in 2013. CONCLUSION: The proportion of
      adult cancer clinical trials in the U.S. requiring a genomic alteration for
      enrollment has increased substantially over the past several years. However, such
      trials still represent a small minority of studies performed within the cancer
      clinical trials enterprise and include a small subset of putatively "actionable"
      alterations.

PMID- 25864025
TI  - Carbon dioxide assisted sustainability enhancement of pyrolysis of waste biomass:
      A case study with spent coffee ground.
AB  - This work mainly presents the influence of CO2 as a reaction medium in the thermo
      chemical process (pyrolysis) of waste biomass. Our experimental work
      mechanistically validated two key roles of CO2 in pyrolysis of biomass. For
      example, CO2 expedited the thermal cracking of volatile organic compounds (VOCs)
      evolved from the thermal degradation of spent coffee ground (SCG) and reacted
      with VOCs. This enhanced thermal cracking behavior and reaction triggered by CO2
      directly led to the enhanced generation of CO (~ 3000%) in the presence of CO2.
      As a result, this identified influence of CO2 also directly led to the
      substantial decrease (~ 40-60%) of the condensable hydrocarbons (tar). Finally,
      the morphologic change of biochar was distinctive in the presence of CO2.
      Therefore, a series of the adsorption experiments with dye were conducted to
      preliminary explore the physico-chemical properties of biochar induced by CO2.

PMID- 25864026
TI  - Combining treatments to improve the fermentation of sugarcane bagasse
      hydrolysates by ethanologenic Escherichia coli LY180.
AB  - Inhibitory side products from dilute acid pretreatment is a major challenge for
      conversion of lignocellulose into ethanol. Six strategies to detoxify sugarcane
      hydrolysates were investigated alone, and in combinations (vacuum evaporation of
      volatiles, high pH treatment with ammonia, laccase, bisulfite, microaeration, and
      inoculum size). High pH was the most beneficial single treatment, increasing the
      minimum inhibitory concentration (measured by ethanol production) from 15%
      (control) to 70% hydrolysate. Combining treatments provided incremental
      improvements, consistent with different modes of action and multiple inhibitory
      compounds. Screening toxicity using tube cultures proved to be an excellent
      predictor of relative performance in pH-controlled fermenters. A combination of
      treatments (vacuum evaporation, laccase, high pH, bisulfite, microaeration)
      completely eliminated all inhibitory activity present in hydrolysate. With this
      combination, fermentation of hemicellulose sugars (90% hydrolysate) to ethanol
      was complete within 48 h, identical to the fermentation of laboratory xylose (50
      g/L) in AM1 mineral salts medium (without hydrolysate).

PMID- 25864027
TI  - Cooperative role of electrical stimulation on microbial metabolism and selection
      of thermophilic communities for p-fluoronitrobenzene treatment.
AB  - A novel thermophilic bioelectrochemical system (TBES) based on electrical
      stimulation was established for the enhanced treatment of p-fluoronitrobenzene (p
      FNB) wastewater. p-FNB removal rate constant in the TBES was 78.6% higher than
      that of the mesophilic BES (MBES), the elevation of which owing to high
      temperature overtook the rate improvement of 50.8% in the electrocatalytic system
      (ECS). Additionally, an overwhelming mineralization efficiency of 91.96% +/-
      5.70% was obtained in the TBES. The superiority of TBES was attributed to the
      integrated role of electrical stimulation and high-temperature. Electrical
      stimulation provided an alternative for the microbial growth independent energy
      requirements, compensating insufficient energy support from p-FNB metabolism
      under the high-temperature stress. Besides, electrical stimulation facilitated
      microbial community evolution to form specific thermophilic biocatalysis. The
      uniquely selected thermophilic microorganisms including Coprothermobacter sp. and
      other ones cooperated to enhance p-FNB mineralization.

PMID- 25864028
TI  - Catalytic fast co-pyrolysis of biomass and food waste to produce aromatics:
      Analytical Py-GC/MS study.
AB  - In this study, catalytic fast co-pyrolysis (co-CFP) of corn stalk and food waste
      (FW) was carried out to produce aromatics using quantitative pyrolysis-gas
      chromatography/mass spectrometry (Py-GC/MS), and ZSM-5 zeolite in the hydrogen
      form was employed as the catalyst. Co-CFP temperature and a parameter called
      hydrogen to carbon effective ratio (H/C(eff) ratio) were examined for their
      effects on the relative content of aromatics. Experimental results showed that co
      CFP temperature of 600  degrees C was optimal for the formation of aromatics and
      other organic pyrolysis products. Besides, H/C(eff) ratio had an important
      influence on product distribution. The yield of total organic pyrolysis products
      and relative content of aromatics increased non-linearly with increasing H/C(eff)
      ratio. There was an apparent synergistic effect between corn stalk and FW during
      co-CFP process, which promoted the production of aromatics significantly. Co-CFP
      of biomass and FW was an effective method to produce aromatics and other
      petrochemicals.

PMID- 25864029
TI  - Enhanced anti-oxidative activity and lignocellulosic ethanol production by biotin
      addition to medium in Pichia guilliermondii fermentation.
AB  - Commercialization of lignocellulosic ethanol fermentation requires its high
      titer, but the reactive oxygen species (ROS) accumulation during the bioprocess
      damaged the cells and compromised this goal. To improve the cellular anti
      oxidative activity during non-detoxified corncob residue hydrolysate
      fermentation, seed cells were prepared to possess a higher level of intracellular
      biotin pool (IBP), which facilitated the biosyntheses of catalase and porphyrin.
      As a result, the catalase activity increased by 1.3-folds compared to control
      while the ROS level reduced by 50%. Cell viability in high-IBP cells was 1.7
      folds of control and the final ethanol titer increased from 31.2 to 41.8 g L(-1)
      in batch fermentation. The high-IBP cells were further used for repeated-batch
      fermentation in the non-detoxified lignocellulosic hydrolysate, and the highest
      titer and average productivity of ethanol reached 63.7 g L(-1) and 1.2 g L(-1)h(
      1). The results were favorable to future industrial application of this
      lignocellulosic bioethanol process.

PMID- 25864030
TI  - A modified BAF system configuring synergistic denitrification and chemical
      phosphorus precipitation: Examination on pollutants removal and clogging
      development.
AB  - The performance of a BAF system configuring simultaneous chemical phosphorus
      precipitation in the pre-denitrification stage was examined using a continuously
      operated setup to treat real domestic wastewater. The effects of using no
      chemical, dosing sole Fe(2+), and dosing combined Fe(2+), PAM, and NaHCO3 in the
      pre-denitrification tank were assessed by monitoring COD, nitrogen, and
      phosphorus removal and hydraulic headloss development in the BAF column. Though
      dosing sole Fe(2+) significantly enhanced phosphorus removal, it would consume
      alkalinity through hydrolysis and form smaller-sized sludge flocs in the pre
      denitrification tank, and hence resulted in affected NH4(+)-N, insoluble COD, and
      SS removal in the BAF. Dosing combined Fe(2+), PAM, and NaHCO3 can enhance sludge
      flocculation to form larger flocs and compensate alkalinity consumption. It
      exhibited sound performance on COD, nitrogen, and phosphorus removal, and led to
      less frequent BAF backwashing by slowing clogging development in the BAF filter
      layer. 

PMID- 25864031
TI  - Methane potential and anaerobic treatment feasibility of Sargassum muticum.
AB  - The aim of this research was to study the feasibility of anaerobic digestion of
      the alga Sargassum muticum with special attention to its biodegradability,
      potential toxicity caused by its salt content, alga components and intermediate
      process compounds, and potential limitations to continuous treatment. Specific
      methane potential (SMP) for three samples of S. muticum collected from the
      Galician coast (Northwest Spain) at different seasons ranged from 166 to 208
      mLCH4/gVS while accumulation of toxic compounds was not observed at alga
      concentrations of up to 100 gTS/L, except for one of the samples in which
      inhibition started at 80-100 gTS/L. Continuous digestion is feasible at alga
      concentration up to 100 gTS/L with methane production rates ranging from 0.14 to
      0.26 LCH4/Ld at organic loading rates of 3.2 gTS/Ld, but SMP dropped to 113-159
      mLCH4/gVS.

PMID- 25864032
TI  - Improving anaerobic digestion of a cellulosic waste via routine bioaugmentation
      with cellulolytic microorganisms.
AB  - This study investigated routine bioaugmentation in the acid-phase of a two-phase
      anaerobic digestion (AD) process treating a largely cellulosic waste material
      generated from sweet corn processing. A proprietary cellulolytic bioculture was
      used for bioaugmentation with the aim of increasing substrate hydrolysis to
      improve overall methanogenic efficiency. In a sequencing batch experiment routine
      bioaugmentation achieved significantly greater soluble chemical oxygen demand
      (sCOD) generation (+25%) and methane production (+15%) compared to one-time
      bioaugmentation. In a continuous bench-scale system, routine bioaugmentation
      increased acid-phase sCOD by 29-68% and acetic acid concentrations by 31-34%.
      This benefit to hydrolysis and acetogenesis subsequently led to sustained
      increase in methane production (+56%) compared to non-bioaugmentation. A cursory
      economic analysis indicated that routine bioaugmentation could improve the
      economics of corn waste AD by $27-$34/dry tonne of waste. Overall, routine
      bioaugmentation showed significant promise for improving AD of corn waste by
      achieving sustained increases in substrate hydrolysis and methane production. 

PMID- 25864033
TI  - Comparative investigation on non-isothermal kinetics for thermo-degradation of
      lignocellulosic substrate and its chlorinated derivative in atmospheres with CO2
      participation.
AB  - Investigations were launched under atmospheres of different N2/CO2 ratios for
      thermo-degradation of lignocellulosic biomass and its chlorinated derivative that
      typically contains 10 wt.% poly(vinyl chloride) (PVC) over thermogravimetric
      analysis. Two degradation stages were found where CO2 was inert in stage one but
      changed to be reactive in stage two. Lignocellulosics were less reactive than
      their chlorinated derivatives. Non-isothermal thermogravimetric data were used
      for evaluating kinetics using Ozawa-Flynn-Wall and Vyazovkin methods. The values
      of apparent activation energy in stage one were 200-250 kJ/mol with less variance
      but varied greatly in stage two for different scenarios concerning CO2 proportion
      and PVC presence. These values were used to determine the reaction mechanism of
      each stage by master-plots method. Most processes were kinetically characterized
      by diffusion and reaction order models. The results afford a theoretical
      groundwork for the resourceful utilization of lignocellulosics derived from
      municipal activities and the development of their thermochemical conversion
      systems.

PMID- 25864034
TI  - Increased delignification by white rot fungi after pressure refining Miscanthus.
AB  - Pressure refining, a pulp making process to separate fibres of lignocellulosic
      materials, deposits lignin granules on the surface of the fibres that could
      enable increased access to lignin degrading enzymes. Three different white rot
      fungi were grown on pressure refined (at 6 bar and 8 bar) and milled Miscanthus.
      Growth after 28 days showed highest biomass losses on milled Miscanthus compared
      to pressure refined Miscanthus. Ceriporiopsis subvermispora caused a
      significantly higher proportion of lignin removal when grown on 6 bar pressure
      refined Miscanthus compared to growth on 8 bar pressure refined Miscanthus and
      milled Miscanthus. RM22b followed a similar trend but Phlebiopsis gigantea SPLog6
      did not. Conversely, C. subvermispora growing on pressure refined Miscanthus
      revealed that the proportion of cellulose increased. These results show that two
      of the three white rot fungi used in this study showed higher delignification on
      pressure refined Miscanthus than milled Miscanthus.

PMID- 25864035
TI  - Simultaneous degradation of toxic refractory organic pesticide and bioelectricity
      generation using a soil microbial fuel cell.
AB  - In this study, the soil microbial fuel cells (MFCs) were constructed in the
      topsoil contaminated with toxic refractory organic pesticide, hexachlorobenzene
      (HCB). The performance of electricity generation and HCB degradation in the soil
      MFCs were investigated. The HCB degradation pathway was analyzed based on the
      determination of degradation products and intermediates. Experimental results
      showed that the HCB removal efficiencies in the three groups (soil MFCs group,
      open circuit control group and no adding anaerobic sludge blank group) were
      71.15%, 52.49% and 38.92%, respectively. The highest detected power density was
      77.5 mW/m(2) at the external resistance of 1000 Omega. HCB was degraded via the
      reductive dechlorination pathway in the soil MFC under anaerobic condition. The
      existence of the anode promoted electrogenic bacteria to provide more electrons
      to increase the metabolic reactions rates of anaerobic bacteria was the main way
      which could promote the removal efficiencies of HCB in soil MFC.

PMID- 25864036
TI  - [Differences in psychiatric expertise of responsibility: Assessment and initial
      hypotheses through a review of literature].
AB  - INTRODUCTION: Forensic psychiatric assessment regarding liability ensures a
      balance between justice and psychiatry. In France, criminal assessment is not
      contradictory. The psychiatric expert is commissioned by judges to determine
      whether or not the accused has a mental disorder and specify whether it affects
      discernment and control of actions at the time of offense. Its mission focuses on
      the mental element required to constitute an offense, and is structured around
      Article 122-1 of the Criminal Code. This article, composed of two paragraphs,
      distinguishes the framework of the abolition of discernment - a cause of non
      imputability and therefore of a statement of lack of criminal responsibility due
      to mental disorder - and the framework of the alteration of discernment. Nowadays
      expertise seems to meet discomfort, with criticism focusing on possible
      differences among psychiatric experts, without specific studies having been
      conducted to confirm it. OBJECTIVES: Our objective was to identify the main
      points of disagreement between psychiatric experts and to propose explicative
      hypotheses. MATERIALS AND METHODS: For this, we carried out a literature review
      on PubMed, Science Direct and Cairn, and studied the report of the 2007 public
      hearing on forensic psychiatric assessment with contributions from different
      authors. The keywords were: forensic psychiatry, psychiatric court report,
      psychiatric expertise, differences among experts, legal responsibility, and
      discernment. We defined differences as disagreements between experts, or as a
      mismatch in conclusions and approaches of experts. RESULTS: The differences among
      experts concerned mainly forensic interpretation, i.e. the discussion of the
      relationship between pathology and offense, particularly in contexts that involve
      a larger forensic discussion, including interruption of medication, use of drugs,
      association with antisocial personality, premeditation, denial of facts,
      especially when the accused suffers from a mental illness (especially
      schizophrenia). For a finding of abolition of discernment, an expert must
      consider two requirements, one temporal (the mental disease must be active during
      offense) and the other causal that involves seeking a direct and exclusive
      relationship between the offence and the mental state, according to expert
      jurisprudence. Some experts do not comply with these two requirements or this
      jurisprudence, whence differences. There were also diagnostic differences and
      disputes relating to the concept of "alteration of discernment". Disagreements
      appeared to be related primarily to personal ideologies or different schools of
      thought that influenced interpretations and conclusions of experts, e.g.
      accountability as a therapeutic response for the psychotic person. Then, the lack
      of clarity of expert mission regarding necessary causal relationship - between
      any disease and crime - to demonstrate to conclude an abolition of discernment,
      could also contribute to differences. Moreover, time available to achieve the
      mission is too short and the expert would not devote enough time to an expert
      examination, which could lead to less good expertise and differences; especially
      as observed clinical examination in expertise is sometimes difficult, misleading,
      due to pathological reticence of accused mentally ill but also sometimes due to
      possible simulations. Finally, the low quality of some expert reports - due in
      part to the less well-trained experts, but also the particular conditions of
      achievement of expertise, especially in prisons - were mentioned by some authors
      as causes of differences. DISCUSSION: It appears from this review of literature
      that differences mainly concern forensic interpretation and are mainly explained
      by ideologies. This synthesis is a preliminary work prior to a study among
      psychiatric experts.

PMID- 25864037
TI  - Predictors of disease-free survival in colorectal cancer with microsatellite
      instability: An AGEO multicentre study.
AB  - BACKGROUND: A microsatellite instability (MSI) phenotype is found in about 12% of
      colorectal cancers (CRCs) and is associated with a low recurrence rate after
      curative surgery. Several studies have identified clinical and pathological
      factors predictive of recurrence in resected CRC, but not in the MSI subgroup.
      PATIENTS AND METHODS: This multicentre retrospective study included patients with
      stage I, II or III MSI CRCs. Disease-free survival (DFS) was calculated with the
      Kaplan-Meier method. Factors associated with DFS were identified in univariate
      and multivariate Cox analyses. RESULTS: We studied 521 patients with MSI CRC.
      Respectively 11%, 51% and 38% of patients were at stage I, II and III. Mean age
      was 68.7years and 36% of the patients received adjuvant chemotherapy. Median
      follow-up was 32.8months. The disease recurrence rates were 6% and 21% in stage
      II and III patients, respectively. The 3-year DFS rate was 77%. In univariate
      analysis, age, bowel obstruction, lymph node invasion, stage T4, vascular emboli,
      lymphatic invasion and perinervous invasion were associated with poorer DFS
      (P<0.05). Three relevant independent predictors of poor DFS were identified in
      multivariate analysis, namely bowel obstruction (HR=2.46; 95%CI 1.31-4.62,
      P=0.005), vascular emboli (HR=2.79; 95%CI 1.74-4.47, P<0.001) and stage T4
      (HR=2.16; 95%CI 1.31-3.56, P=0.002). CONCLUSIONS: Bowel obstruction, vascular
      emboli and stage T4 are independently associated with MSI CRC recurrence,
      suggesting that screening for vascular emboli in routine clinical practice may
      assist with adjuvant chemotherapy decision-making.

PMID- 25864038
TI  - KRAS as a predictor of poor prognosis and benefit from postoperative FOLFOX
      chemotherapy in patients with stage II and III colorectal cancer.
AB  - PURPOSE: The KRAS gene frequently mutates in colorectal cancer (CRC). Here we
      investigated the prognostic and predictive role of KRAS mutation in patients with
      stage II or III CRC. EXPERIMENTAL DESIGN: A consecutive cohort of patients with
      stage II or III CRC from a single center database was studied. The association
      between KRAS status, adjuvant FOLFOX therapy, and 3-year disease-free survival (3
      y DFS) was analyzed. RESULTS: Of our 433 patients, 166 (38.3%) exhibited the KRAS
      mutation. Among the 190 patients who did not receive adjuvant therapy, those with
      KRAS mutation tumors had a worse 3-y DFS (hazard ratio [HR], 1.924; 95%
      confidence interval [CI], 1.078-3.435; P = 0.027). Among patients who received
      adjuvant chemotherapy, KRAS mutation was not correlated with worse 3-y DFS (HR,
      1.083; 95% CI, 0.618-1.899; P = 0.781). Adjuvant chemotherapy improved 3-y DFS
      only among patients with KRAS mutant tumors (78.0% vs 69.2%) on multivariate
      analysis adjusted for age, stage, grade, site, vessel invasion, and
      carcinoembryonic antigen level (HR, 0.454; 95% CI, 0.229-0.901; P = 0.024). In
      contrast, there was no benefit of adjuvant chemotherapy in the KRAS wild-type
      group (84.3% vs 82.0%). CONCLUSIONS: KRAS mutation indicates poor prognosis.
      FOLFOX adjuvant chemotherapy benefits patients with stage II or III colorectal
      cancer with KRAS mutant tumors and is worth further investigation.

PMID- 25864040
TI  - Comparison of two numerical modelling approaches to a field experiment of
      unsaturated radon transport in a covered uranium mill tailings soil (Lavaugrasse,
      France).
AB  - Uncertainties on the mathematical modelling of radon ((222)Rn) transport in an
      unsaturated covered uranium mill tailings (UMT) soil at field scale can have a
      great impact on the estimation of the average measured radon exhalation rate to
      the atmosphere at the landfill cover. These uncertainties are usually attributed
      to the numerical errors from numerical schemes dealing with soil layering, and to
      inadequate modelling of physical processes at the soil/plant/atmosphere interface
      and of the soil hydraulic and transport properties, as well as their
      parameterization. In this work, we demonstrate how to quantify these
      uncertainties by comparing simulation results from two different numerical models
      to experimental data of radon exhalation rate and activity concentration in the
      soil-gas measured in a covered UMT-soil near the landfill site Lavaugrasse
      (France). The first approach is based on the finite volume compositional (i.e.,
      water, radon, air) transport model TOUGH2/EOS7Rn (Transport Of Unsaturated
      Groundwater and Heat version 2/Equation Of State 7 for Radon; Saadi et al.,
      2014), while the second one is based on the finite difference one-component
      (i.e., radon) transport model TRACI (Transport de RAdon dans la Couche Insaturee;
      Ferry et al., 2001). Transient simulations during six months of variable rainfall
      and atmospheric air pressure showed that the model TRACI usually overestimates
      both measured radon exhalation rate and concentration. However, setting effective
      unsaturated pore diffusivities of water, radon and air components in soil-liquid
      and gas to their physical values in the model EOS7Rn, allowed us to enhance
      significantly the modelling of these experimental data. Since soil evaporation
      has been neglected, none of these two models was able to simulate the high radon
      peaks observed during the dry periods of summer. However, on average, the radon
      exhalation rate calculated by EOS7Rn was 34% less than that was calculated by
      TRACI, and much closer to the measured one for physically-based soil radon
      diffusion models. Unlike TRACI, EOS7Rn was able to simulate qualitatively
      seasonal variations of both radon exhalation and concentration. These results
      show that EOS7Rn produces less numerical errors than TRACI, and can be considered
      as a promising model for predicting radon transport in the landfill, if soil
      evaporation is modelled and its numerical inversion for parameter estimation is
      realized. 

PMID- 25864039
TI  - Comprehensive analysis of microRNA expression profile in malignant glioma
      tissues.
AB  - Malignant gliomas represent the most devastating group of brain tumors in adults,
      among which glioblastoma multiforme (GBM) exhibits the highest malignancy rate.
      Despite combined modality treatment, GBM recurs and is invariably fatal. A
      further insight into the molecular background of gliomagenesis is required to
      improve patient outcomes. The primary aim of this study was to gain broad
      information on the miRNA expression pattern in malignant gliomas, mainly GBM. We
      investigated the global miRNA profile of malignant glioma tissues with miRNA
      microarrays, deep sequencing and meta-analysis. We selected miRNAs that were most
      frequently deregulated in glioblastoma tissues, as well as in peritumoral areas,
      in comparison with normal human brain. We identified candidate miRNAs associated
      with the progression from glioma grade III to glioma grade IV. The meta-analysis
      of miRNA profiling studies in GBM tissues summarizes the past and recent advances
      in the investigation of the miRNA signature in GBM versus noncancerous human
      brain and provides a comprehensive overview. We propose a list of 35 miRNAs whose
      expression is most frequently deregulated in GBM patients and of 30 miRNA
      candidates recognized as novel GBM biomarkers. 

PMID- 25864041
TI  - Recent advancements in sensing techniques based on functional materials for
      organophosphate pesticides.
AB  - The use of organophosphate pesticides (OPs) for pest control in agriculture has
      caused serious environmental problems throughout the world. OPs are highly toxic
      with the potential to cause neurological disorders in humans. As the application
      of OPs has greatly increased in various agriculture activities, it has become
      imperative to accurately monitor their concentration levels for the protection of
      ecological systems and food supplies. Although there are many conventional
      methods available for the detection of OPs, the development of portable sensors
      is necessary to facilitate routine analysis with more convenience. Some of these
      potent alternative techniques based on functional materials include fluorescence
      nanomaterials based sensors, molecular imprinted (MIP) sensors, electrochemical
      sensors, and biosensors. This review explores the basic features of these sensing
      approaches through evaluation of their performance. The discussion is extended
      further to describe the challenges and opportunities for these unique sensing
      techniques. 

PMID- 25864042
TI  - Association of dual-antiplatelet therapy with reduced major adverse
      cardiovascular events in patients with symptomatic peripheral arterial disease.
AB  - OBJECTIVE: This study was conducted to determine whether there is additive
      benefit of dual-antiplatelet therapy (DAPT) with aspirin (acetylsalicylic acid
      [ASA]) and clopidogrel compared with ASA monotherapy among patients with
      symptomatic peripheral arterial disease. METHODS: This was an observational
      cohort analysis that included 629 patients with claudication or critical limb
      ischemia. The prevalence of patients taking ASA monotherapy vs DAPT was assessed
      monthly for up to 3 years. A propensity model was constructed to adjust for
      baseline demographic characteristics and to assess the effect of DAPT on major
      adverse cardiovascular events (MACEs) and major adverse limb events. RESULTS: At
      baseline, 348 patients were taking DAPT and 281 were taking ASA monotherapy.
      During 3 years of follow-up, 50 events (20%) occurred in the DAPT group vs 59
      (29%) in the ASA monotherapy group. After propensity weighting, DAPT use was
      associated with a decreased risk of MACEs (adjusted hazard ratio [HR], 0.65; 95%
      confidence interval [CI], 0.44-0.96) and overall mortality (adjusted HR, 0.55;
      95% CI, 0.35-0.89). No association was found between DAPT use and the risk of
      major amputation (adjusted HR, 0.69; 95% CI, 0.37-1.29). In a subgroup of 94
      patients who underwent point-of-care platelet function testing, 21% had decreased
      response to ASA and 55% had a decreased response to clopidogrel. No association
      was found between a reduced response to ASA or clopidogrel and adverse events at
      1 year. CONCLUSIONS: DAPT may be associated with reduced rates of MACEs and death
      among patients with symptomatic peripheral arterial disease.

PMID- 25864043
TI  - Anatomic and clinical predictors of reintervention after subclavian artery
      stenting.
AB  - OBJECTIVE: This study was conducted to determine long-term predictors of target
      lesion reintervention (TLR) after subclavian artery stenting (SAS). METHODS: This
      was a single-center retrospective review of patients with symptomatic
      atherosclerotic subclavian artery disease who underwent SAS between January 1999
      and December 2013. Repeat intervention was only performed in patients with
      recurrent symptoms and >=70% in-stent restenosis (ISR). TLR was defined as need
      for a repeat percutaneous intervention involving a previously stented area.
      Freedom from events (ISR and TLR) was analyzed using Kaplan-Meier curves. Cox
      regression analysis was used to determine the significant predictors of TLR and
      ISR. RESULTS: Index procedures were performed on 139 arteries in 138 patients
      (69.6% female). Patients were an average age of 64.5 years, with major
      comorbidities of hypertension (80.4%), hyperlipidemia (72.5%), and tobacco use
      (60.1%). Also performed during the study period were 24 TLR procedures, resulting
      166 SAS interventions attempted for patients with subclavian atherosclerotic
      disease during a 15-year span. Of 166 procedures, 163 (98.2%) were treated
      successfully. Stents were placed in all but two index arteries. The main
      indications for SAS were subclavian steal syndrome (48.9%), arm claudication
      (21.6%), and coronary steal syndrome (28.8%). The average preprocedure stenosis
      was 87.2% +/- 11.2%. For index procedures (139 arteries), duplex follow-up was
      available for 134 arteries (96.4%), with an overall ISR rate of 18.7% (25 of
      134). Primary patency for the index procedures was 84.7% at 10 years. The overall
      TLR rate for the index procedures was 12.7% (17 cases). Seven patients required
      more than one secondary procedure. For all cases, the freedom from ISR was 91%,
      77%, and 68% at 1, 5, and 10 years, respectively, and freedom from TLR was 94%,
      85%, and 82% at 1, 5, and 10 years, respectively. Multivariate analysis showed
      the significant predictors of ISR were smoking/chronic obstructive pulmonary
      disease (hazard ratio [HR], 3.2; P = .001), age by decade (HR, 0.5; P < .001),
      discharged with statin therapy (HR, 0.3; P = .001), vessel diameter <=7 mm (HR,
      2.3; P = .028), and right-sided intervention (HR, 0.3; P = .040). The sole
      significant predictor of TLR was age by decade (HR, 0.6; P = .008). CONCLUSIONS:
      SAS has a high primary success and durability with satisfactory outcomes well
      beyond 10 years. ISR was more likely to develop in patients who were smokers with
      chronic obstructive disease or had a baseline vessel size of <=7 mm. Younger age
      could be an independent risk factor for secondary intervention.

PMID- 25864044
TI  - Predictors of compliance with surveillance after endovascular aneurysm repair and
      comparative survival outcomes.
AB  - OBJECTIVE: Although imaging surveillance is mandatory for all patients after
      endovascular aneurysm repair (EVAR), many patients are not compliant with follow
      up. We sought to determine predictors of compliance with EVAR surveillance and to
      examine how compliance with current surveillance protocols correlates with
      survival. METHODS: We analyzed 188 patients who underwent EVAR at our institution
      for infrarenal abdominal aortic aneurysms (AAAs) between 2001 and 2011. The
      primary end point was compliance with post-EVAR surveillance recommendations.
      Univariate analysis included patient demographics and socioeconomic information,
      AAA characteristics, EVAR hospital course variables, late complications and
      secondary interventions, length of follow-up, smoking status, family history of
      AAA, driving distances, primary care providers, and medical comorbidities.
      Mortality was determined by the Social Security Death Index. Multinomial logistic
      regressions were fit to identify independent predictors of compliance. Survival
      plots were generated with the Kaplan-Meier method and compared with the log-rank
      test. Univariate and multivariate Cox regression analysis was used to determine
      effect of compliance on survival after adjusting for confounders. RESULTS: Of 188
      patients, 89 (47.3%) were 100% compliant with follow-up visits and imaging, 21
      (11.1%) were moderately compliant by missing appointments, and 78 (41.4%) were
      lost to follow-up completely. Overall median age was 74 years, and 81.9% of
      patients were male. Late complications occurred in 77 patients (40.9%), secondary
      interventions were performed in 32 patients (17%), and 5-year mortality was
      21.2%. Mean follow-up interval was >40 months for 100% compliant and moderately
      compliant patients and <20 months for those lost to follow-up (P < .0001). In
      adjusted analysis, late complications (odds ratio [OR], 2.71; 95% confidence
      interval [CI], 1.32-5.55; P = .007), absence of social work consultation (OR,
      2.43; 95% CI, 1.12-5.27; P = .024), and family history of AAA (OR, 2.67; 95% CI,
      1.06-6.75; P = .037) were associated with 100% compliance, whereas shorter
      driving distances (P = .051) and shorter hospital stay (P = .056) approached
      significance. Transient ischemic attack or stroke (OR, 3.59; 95% CI, 1.18-10.91;
      P = .024) was the only variable independently associated with moderate
      compliance. Compared with patients lost to follow-up, 100% compliant patients had
      worse survival (log-rank test, P = .033), whereas moderately compliant patients'
      survival was not significantly different (log-rank test, P = .149). In adjusted
      Cox regression analysis, 100% compliant patients had decreased survival duration
      (rate ratio, 2.67; 95% CI, 1.18-6.06; P = .018) compared with those lost to
      follow-up. CONCLUSIONS: Follow-up surveillance is incomplete for more than half
      of patients who undergo EVAR at our institution, and patient compliance can be
      predicted by covariates mentioned before. Compliance with current surveillance
      regimens does not confer a survival benefit. Further research individualizing
      surveillance protocols based on risk level of late complications and
      noncompliance and prospective studies examining resulting survival benefits of
      compliance are warranted.

PMID- 25864045
TI  - Custom fenestration templates for endovascular repair of juxtarenal aortic
      aneurysms.
AB  - Physician-modified endovascular grafts, with fenestrations added to accommodate
      major branch vessels, provide a means for endovascular treatment of abdominal
      aortic aneurysms that are adjacent to the renal arteries. Manual measurements of
      vessel origin locations from computed tomography images, however, take time and
      can lead to errors in the positions of the fenestrations. To make the
      fenestration process faster and more accurate, we have developed a procedure to
      create custom templates that serve as patient-specific guides for graft
      fenestration. We use a three-dimensional printer to create a clear rigid sleeve
      that replicates the patient's aorta and includes holes placed precisely at the
      locations of the branch vessels. The sleeve is slipped over the graft, the
      locations of the openings are marked with a pen, and the fenestrations are
      created after the sleeve is removed. Custom fenestration templates can
      potentially save procedural costs and make minimally invasive aortic aneurysm
      repair available to more patients. 

PMID- 25864046
TI  - Public health system and psychiatry in the treatment of 'dangerous' young
      offenders in Brazil.
AB  - We describe the Experimental Health Unit, a special forensic mental health
      facility in Brazil, created by court order and administered by the Sao Paulo
      Department of Health. It was designed for young offenders receiving compulsory
      inpatient treatment for severe personality disorders. All nine patients admitted
      to date came from Foundation CASA (a socio-educational centre of assistance for
      adolescents, the juvenile correctional centres managed by the Sao Paulo state
      Department of Justice). The court decision is questionable, relying on a new
      interpretation of the Child and Adolescent Statute and the law that regulates
      psychiatric treatment in Brazil. The public health system and psychiatry have
      been supporting the isolation of some individuals from society, based on the
      seriousness of their crimes and possession of particular personality
      characteristics. The decision to commit and send a small group of personality
      disordered individuals to this unit as inpatients is an unfair decision, since
      jails and correctional centres hold a high number of psychopathic who have also
      committed barbaric crimes. The central mental health issue is the role that the
      public health system should play in the custody of dangerous people; the cost
      effectiveness of this model, the accuracy of risk assessment and tractability of
      people with severe personality disorders are also debatable. From a legal
      perspective, the operation of this facility raises questions about age of legal
      majority, the maximum period of incarceration of young offenders and use of whole
      life sentences for certain types of crimes and criminals in Brazil. 

PMID- 25864047
TI  - Direct visualization of vaults within intact cells by electron cryo-tomography.
AB  - The vault complex is the largest cellular ribonucleoprotein complex ever
      characterized and is present across diverse Eukarya. Despite significant
      information regarding the structure, composition and evolutionary conservation of
      the vault, little is know about the complex's actual biological function. To
      determine if intracellular vaults are morphologically similar to previously
      studied purified and recombinant vaults, we have used electron cryo-tomography to
      characterize the vault complexes found in the thin edges of primary human cells
      growing in tissue culture. Our studies confirm that intracellular vaults are
      similar in overall size and shape to purified and recombinant vaults previously
      analyzed. Results from subtomogram averaging indicate that densities within the
      vault lumen are not ordered, but randomly distributed. We also observe that
      vaults located in the extreme periphery of the cytoplasm predominately associate
      with granule-like structures and actin. Our ultrastructure studies augment
      existing biochemical, structural and genetic information on the vault, and
      provide important intracellular context for the ongoing efforts to understand the
      biological function of the native cytoplasmic vault. 

PMID- 25864048
TI  - Analyzing the heterogeneity of farmers' preferences for improvements in dairy cow
      traits using farmer typologies.
AB  - Giving consideration to farmers' preferences for improvements in animal traits
      when designing genetic selection tools such as selection indexes might increase
      the uptake of these tools. The increase in use of genetic selection tools will,
      in turn, assist in the realization of genetic gain in breeding programs. However,
      the determination of farmers' preferences is not trivial because of its large
      heterogeneity. The aim of this study was to quantify Australian dairy farmers'
      preferences for cow trait improvements to inform and ultimately direct the choice
      of traits and selection indexes in the 2014 review of the National Breeding
      Objective. A specific aim was to analyze the heterogeneity of preferences for cow
      trait improvements by determining whether there are farmer types that can be
      identified with specific patterns of preferences. We analyzed whether farmer
      types differed in farming system, socioeconomic profile, and attitudes toward
      breeding and genetic evaluation tools. An online survey was developed to explore
      farmers' preferences for improvement in 13 cow traits. The pairwise comparisons
      method was used to derive a ranking of the traits for each respondent. A total of
      551 farmers fully completed the survey. A principal component analysis followed
      by a Ward hierarchical cluster analysis was used to group farmers according to
      their preferences. Three types of farmers were determined: (1) production-focused
      farmers, who gave the highest preference of all for improvements in protein
      yield, lactation persistency, feed efficiency, cow live weight, and milking
      speed; (2) functionality-focused farmers with the highest preferences of all for
      improvements in mastitis, lameness, and calving difficulty; and (3) type-focused
      farmers with the highest preferences of all for mammary system and type. Farmer
      types differed in their age, their attitudes toward genetic selection, and in the
      selection criteria they use. Surprisingly, farmer types did not differ for herd
      size, calving, feeding system, or breed. These results support the idea that
      preferences for cow trait improvements are intrinsic to farmers and not to
      production systems or breeds. As a result of this study, and some bioeconomic
      modeling (not included in this study), the Australian dairy industry has
      implemented a main index and 2 alternative indexes targeting the different farmer
      types described here. 

PMID- 25864049
TI  - Increasing estradiol benzoate, pretreatment with gonadotropin-releasing hormone,
      and impediments for successful estradiol-based fixed-time artificial insemination
      protocols in dairy cattle.
AB  - With the objective to optimize fixed-time artificial insemination (FTAI)
      protocols based on estradiol benzoate (EB) and progesterone (P4), we performed 2
      experiments (Exp.) in dairy cows. In Exp. 1 (n=44), we hypothesized that
      increased EB (EB3=3 mg vs. EB2=2 mg) on d 0 would improve synchronization of
      ovarian follicle wave emergence. Likewise, in Exp. 2 (n=82), we hypothesized that
      a GnRH treatment on d -3 (early in a follicular wave on d 0) versus d -7
      (presence of a dominant follicle on d 0) would better synchronize wave emergence.
      Moreover, results from both experiments were combined to identify reasons for the
      lack of synchronization. All cows were treated with EB at the time of
      introduction of a P4 implant (d 0). On d 7, cows were given 25 mg of
      prostaglandin F2alpha; on d 8, the implant was removed and cows were given 1mg of
      estradiol cypionate. All cows received FTAI on d 10. In both experiments, daily
      ultrasound evaluations were performed and, in Exp. 2, circulating P4 was
      evaluated during the protocol. Pregnancy per artificial insemination (P/AI) was
      determined on d 31 and 59 after FTAI. In Exp. 1, EB dose did not change time to
      wave emergence, but EB3 compared with EB2 decreased the percentage of cows with a
      corpus luteum on d 7 (19.8 vs. 55.3%) and time to ovulation (10.4 vs. 10.9 d). In
      Exp. 2, although we detected a tendency for delayed follicle wave emergence after
      the start of the FTAI protocol in cows ovulating to GnRH given on d -7, there was
      no difference in percentage of cows with a synchronized wave emergence (~80%).
      Regardless of treatment, more cows with P4<0.1 ng/mL, compared with P4>=0.1 and
      <0.22 ng/mL at the time of AI, ovulated to the protocol (81.2 vs. 58.0%) and had
      increased P/AI (47.4 vs. 21.4%). An analysis of data from both experiments showed
      that only 73.8% (93/126) of cows had synchronized wave emergence, and only 77.8%
      (98/126) of cows ovulated at the end of the protocol. Fertility was much greater
      in cows that had emergence of a new wave synchronized and ovulated to end of the
      protocol [P/AI 61.3% (46/75)] compared with cows that failed to present one or
      both of the outcomes above [15.7% (8/51)]. Thus, although current FTAI protocols
      using EB and P4 produce P/AI between 30 and 40% for lactating dairy cows, there
      remains room for improvement because less than 60% (75/126) of the cows were
      correctly synchronized. Starting the FTAI protocol without the dominant follicle
      or increasing the dose of EB to 3mg was not effective in increasing
      synchronization rate.

PMID- 25864050
TI  - Hot topic: Use of genomic recursions in single-step genomic best linear unbiased
      predictor (BLUP) with a large number of genotypes.
AB  - The purpose of this study was to evaluate the accuracy of genomic selection in
      single-step genomic BLUP (ssGBLUP) when the inverse of the genomic relationship
      matrix (G) is derived by the "algorithm for proven and young animals" (APY). This
      algorithm implements genomic recursions on a subset of "proven" animals. Only a
      relationship matrix for animals treated as "proven" needs to be inverted, and the
      extra costs of adding animals treated as "young" are linear. Analyses involved
      10,102,702 final scores on 6,930,618 Holstein cows. Final score, which is a
      composite of type traits, is popular trait in the United States and was easily
      available for this study. A total of 100,000 animals with genotypes were used in
      the analyses and included 23,000 sires (16,000 with >5 progeny), 27,000 cows, and
      50,000 young animals. Genomic EBV (GEBV) were calculated with a regular inverse
      of G, and with the G inverse approximated by APY. Animals in the proven subset
      included only sires (23,000), sires+cows (50,000), only cows (27,000), or sires
      with >5 progeny (16,000). The correlations of GEBV with APY and regular GEBV for
      young genotyped animals were 0.994, 0.995, 0.992, and 0.992, respectively Later,
      animals in the proven subset were randomly sampled from all genotyped animals in
      sets of 2,000, 5,000, 10,000, 15,000, and 20,000; each sample was replicated 4
      times. Respective correlations were 0.97 (5,000 sample), 0.98 (10,000 sample),
      and 0.99 (20,000 sample), with minimal difference between samples of the same
      size. Genomic EBV with APY were accurate when the number of animals used in the
      subset is between 10,000 and 20,000, with little difference between the ways of
      creating the subset. Due to the approximately linear cost of APY, ssGBLUP with
      APY could support any number of genotyped animals without affecting accuracy.

PMID- 25864051
TI  - Effect of replacing alfalfa with panicled-tick clover or sericea lespedeza in
      corn-alfalfa-based substrates on in vitro ruminal methane production.
AB  - Methane emissions from ruminant livestock contribute to total anthropogenic
      greenhouse gas emissions and reduce metabolizable energy intake by the animal.
      Condensed tannins (CT) are polyphenolic plant secondary compounds commonly
      produced by some perennial forage legumes that characteristically bind to
      protein, carbohydrates, and minerals. The degree to which CT may affect ruminant
      nutrition depends upon the concentration, structural composition, and biological
      activity of the CT. The objective of our experiment was to determine the effect
      of replacing alfalfa in a corn-alfalfa-based substrate with a legume containing
      CT on in vitro CH4 production and the dynamics of fermentation using an in vitro
      gas production technique. All fermented substrates contained 50% ground corn as
      the energy concentrate portion, whereas the forage portion (50%) of each diet was
      comprised of alfalfa (control) or some combination of alfalfa and sericea
      lespedeza (SL) or panicled-tick clover (PTC). Our treatments consisted of PTC or
      SL 15, 30, and 45, which corresponded with 15, 30, or 45% replacement of the diet
      (alfalfa component) with either PTC or SL. Substrates containing 45% PTC or SL
      reduced in vitro CH4 production. Treatments did not affect total gas production
      as compared with that of the control. Replacement of alfalfa with SL or PTC
      increased fermentable organic matter (FOM). The PTC treatment increased FOM by as
      much as 1.8% at the 45% replacement level, whereas FOM of SL 45 was increased by
      less than 1%. The replacement of alfalfa with PTC increased substrate nutritive
      value greater than replacement with SL. There were no correlations between any
      physicochemical constituent of the substrates and CH4 production. A combination
      of factors associated with the inclusion of PTC and SL contributed to the in
      vitro CH4 production, and CT in these forages was likely a major contributing
      factor. Further confirmation of these results on in situ or in vivo animal
      systems is required. If proven effective in an in vivo production scenario,
      replacement of commonly fed non-CT-containing legumes, such as alfalfa, with
      legumes containing CT might be a viable method to decrease the effect of animal
      agriculture on greenhouse gas production. 

PMID- 25864052
TI  - Exploring the characteristics and dynamics of Ontario dairy herds experiencing
      increases in bulk milk somatic cell count during the summer.
AB  - Regionally aggregated bulk milk somatic cell count (BMSCC) data from around the
      world shows a repeatable cyclicity, with the highest levels experienced during
      warm, humid seasons. No studies have evaluated this seasonal phenomenon at the
      herd level. The objectives of this study were to define summer seasonality in
      BMSCC on an individual herd basis, and subsequently to describe the
      characteristics and dynamics of herds with increased BMSCC in the summer. The
      data used for this analysis were from all dairy farms in Ontario, Canada, between
      January 2000 and December 2011 (n~4,000 to 6,000 herds/yr). Bulk milk data were
      obtained from the milk marketing board and consisted of bulk milk production,
      components (fat, protein, lactose, other solids), and quality (BMSCC, bacterial
      count, inhibitor presence, freezing point), total milk quota of the farm, and
      milk quota and incentive fill percentage. A time-series linear mixed model, with
      random slopes and intercepts, was constructed using sine and cosine terms as
      predictors to describe seasonality, with herd as a random effect. For each herd,
      seasonality was described with reference to 1 cosine function of variable
      amplitude and phase shift. The predicted months of maximal and minimal BMSCC were
      then calculated. Herds were assigned as low, medium, and high summer increase
      (LSI, MSI, and HSI, respectively) based on percentiles of amplitude in BMSCC
      change for each of the 4 seasons. Using these seasonality classifications, 2
      transitional repeated measures logistic regression models were built to assess
      the characteristics of MSI and HSI herds, using LSI herds as controls. Based on
      the analyses performed, a history of summer BMSCC increases increased the odds of
      experiencing a subsequent increase. As herd size decreased, the odds of
      experiencing HSI to MSI in BMSCC increased. Herds with more variability in daily
      BMSCC were at higher odds of experiencing MSI and HSI in BMSCC, as were herds
      with lower annual mean BMSCC. Finally, a negative association was noted between
      filling herd production targets and experiencing MSI to HSI in BMSCC. These
      findings provide farm advisors direction for predicting herds likely to
      experience increases in SCC over the summer, allowing them to proactively focus
      udder health prevention strategies before the high-risk summer period.

PMID- 25864053
TI  - Novel cellobiose 2-epimerases for the production of epilactose from milk
      ultrafiltrate containing lactose.
AB  - A selected number of enzymes have recently been assigned to the emerging class of
      cellobiose 2-epimerases (CE). All CE convert lactose to the rare sugar
      epilactose, which is regarded as a new prebiotic. Within this study, the gene
      products of 2 potential CE genes originating from the mesophilic bacteria
      Cellulosilyticum lentocellum and Dysgonomonas gadei were recombinantly produced
      in Escherichia coli and purified by chromatography. The enzymes have been
      identified as novel CE by sequence analysis and biochemical characterizations.
      The biochemical characterizations included the determination of the molecular
      weight, the substrate spectrum, and the kinetic parameters, as well as the pH and
      temperature profiles in buffer and food matrices. Both identified CE epimerize
      cellobiose and lactose into the C2 epimerization products glucosylmannose and
      epilactose, respectively. The epimerization activity for lactose was maximal at
      pH 8.0 or 7.5 and 40 degrees C in defined buffer systems for the CE from C.
      lentocellum and the CE from D. gadei, respectively. In addition,
      biotransformations of the foodstuff milk ultrafiltrate containing lactose were
      demonstrated. The CE from D. gadei was produced in a stirred-tank reactor (12 L)
      and purified using an automatic system. Enzyme production and purification in
      this scale indicates that a future upscaling of CE production is possible. The
      bioconversions of lactose in milk ultrafiltrate were carried out either in a
      batch process or in a continuously operated enzyme membrane reactor (EMR)
      process. Both processes ran at an industrially relevant low temperature of 8
      degrees C to reduce undesirable microbial growth. The enzyme was reasonably
      active at the low process temperature because the CE originated from a mesophilic
      organism. An epilactose yield of 29.9% was achieved in the batch process within
      28 h of operation time. In the continuous EMR process, the epilactose yield in
      the product stream was lower, at 18.5%. However, the enzyme productivity was
      approximately 6 times higher because the continuous epilactose formation was
      carried out for about 6 d without further addition of biocatalyst. Within this
      time, 24g of epilactose in 2.8 L of permeate were produced. The batch and the EMR
      process showed that the milk ultrafiltrate, which is a sidestream of the milk
      protein production, might be upgraded to a dairy product of higher value by the
      enzymatic in situ production of epilactose. 

PMID- 25864054
TI  - Short communication: Macrocyclic lactone residues in butter from Brazilian
      markets.
AB  - Macrocyclic lactones (ML) are commonly used in drug formulations for the
      treatment of parasites in cattle. In Brazil, except for drugs (or formulations)
      with long-term (half-life) effects, ML are registered for use in bovines.
      Indiscriminate use of ML may result in the presence of residues in milk and dairy
      products due to their lipophilic properties and thermal stability. This study
      applied a method of liquid chromatography with fluorimetric detection, recently
      developed and validated for the determination of residues of abamectin,
      doramectin, ivermectin, and moxidectin in butter. The method was applied to 38
      samples of commercial butter purchased in the metropolitan area of Rio de
      Janeiro, Brazil, between June and September 2013, analyzed in triplicate.
      Ivermectin was detected in 89.5% of the samples, with concentrations between 0.3
      and 119.4 ug/kg; 76.3% of the samples contained doramectin (0.6 to 64.7 ug/kg)
      and 55.2% contained abamectin (0.7 to 4.5 ug/kg). Most butter samples (76.3%)
      contained residues of more than 1 ML; however, no residues of moxidectin were
      detected. The results showed a high incidence of the presence of avermectins in
      butter samples. Butter is not included in the Brazilian National Plan for Control
      of Residues and Contaminants in Animal Products. As ML residues concentrate in
      lipophilic compounds, butter and other fatty dairy products should be screened
      for the presence of ML residues.

PMID- 25864055
TI  - Changes in mammary metabolism in response to the provision of an ideal amino acid
      profile at 2 levels of metabolizable protein supply in dairy cows: Consequences
      on efficiency.
AB  - The aim of this study was to compare the modifications in mammary gland
      metabolism by supplying an ideal versus an imbalanced essential AA (EAA) profile
      at low and high metabolizable protein (or PDIE, its equivalent in the INRA
      feeding system). Four lactating, multiparous Holstein cows received 4 treatments
      composed of 2 basal diets containing 2 levels of PDIE (LP or HP) and 2 different
      infusions of AA mixtures (AA- or AA+) in the duodenum. The AA+ mixture contained
      Lys, Met, Leu, His, Ile, Val, Phe, Arg, Trp, and Glu, whereas the AA- mixture
      contained Glu, Pro, and Ser. The infusion mixtures were iso-PDIE. The diet plus
      infusions provided 13.9 versus 15.8% of crude protein that corresponded to 102
      versus 118g/kg of dry matter of PDIE in LP and HP treatments, respectively. The
      treatments were designed as a 2*2 crossover design of 2 levels of PDIE supply (LP
      vs. HP) with 28-d periods. Infusions of AA in the duodenum (AA- vs. AA+) were
      superimposed to diet within each 28-d period according to 2*2 crossover designs
      with 14-d subperiods. Increasing the PDIE supply tended to increase milk protein
      yield; however, the efficiency of PDIE utilization decreased and the plasma urea
      concentration increased, indicating a higher catabolism of AA. The AA+ treatments
      increased milk protein yield and content similarly at both levels of protein
      supply. This was explained by an increase in the mammary uptake of all EAA except
      His and Trp. The mammary uptake of non-EAA (NEAA) was altered to the increase in
      EAA uptake so that the total AA uptake was almost equal to milk protein output on
      a nitrogen basis. The ratio between NEAA to total AA uptake decreased from 46% in
      LPAA- to 40% in LPAA+, HPAA-, and HPAA+ treatments. The PDIE efficiency tended to
      increase in the AA+ versus the AA- treatments because the NEAA supply and the
      amount of NEAA not used by the mammary both decreased. Nevertheless, our AA+
      treatments seemed not to be the ideal profile: the mammary uptake-to-output ratio
      for Thr was higher than 1 in LPAA-, but it decreased to 1 in all the other
      treatments, suggesting that Thr was deficient in these treatments. Conversely, an
      excess of His was indicated because its uptake was similar in AA+ and AA-
      treatments. In conclusion, balancing the EAA profile increased milk protein yield
      and metabolizable protein efficiency at both levels of protein supply by
      increasing the mammary uptake of EAA and altering the NEAA uptake, leading to
      less AA available for catabolism. 

PMID- 25864056
TI  - Changes in human gut microbiota influenced by probiotic fermented milk ingestion.
AB  - We investigated the effect of consuming probiotic fermented milk (PFM) on the
      microbial community structure in the human intestinal tract by using high
      throughput barcoded pyrosequencing. Six healthy adults ingested 2 servings of PFM
      daily for 3 wk, and their fecal microbiota were analyzed before and after 3 wk of
      PFM ingestion period and for another 3 wk following the termination of PFM
      ingestion (the noningestion period). Fecal microbial communities were
      characterized by sequencing of the V1-V3 hypervariable regions of the 16S rRNA
      gene. All subjects showed a similar pattern of microbiota at the phylum level,
      where the relative abundance of Bacteriodetes species increased during the PFM
      ingestion period and decreased during the noningestion period. The increase in
      Bacteroidetes was found to be due to an increase in members of the families
      Bacteroidaceae or Prevotellaceae. In contrast to PFM-induced adaptation at the
      phylum level, the taxonomic composition at the genus level showed a considerable
      alteration in fecal microbiota induced by PFM ingestion. As revealed by analysis
      of operational taxonomic units (OTU), the numbers of shared OTU were low among
      the 3 different treatments (before, during, and after PFM ingestion), but the
      abundance of the shared OTU was relatively high, indicating that the majority
      (>77.8%) of total microbiota was maintained by shared OTU during PFM ingestion
      and after its termination. Our results suggest that PFM consumption could alter
      microbial community structure in the gastrointestinal tract of adult humans while
      maintaining the stability of microbiota.

PMID- 25864057
TI  - Compositional and sensory differences of products of sweet-cream and whey
      buttermilk produced by microfiltration, diafiltration, and supercritical CO2.
AB  - The objectives of this work were to assess the compositional properties and
      sensory characteristics of ingredients produced by treating sweet-cream and whey
      cream buttermilks with microfiltration (MF), diafiltration (DF), and
      supercritical CO2 (SFE) extraction. Sweet-cream buttermilk (CBM) and buttermilk
      resulting from churning the residual fat from whey processing (whey buttermilk,
      WBM) were used. Using MF or microfiltration followed by diafiltration (MF-DF), we
      obtained resulting retentates that were dried and then were subjected to SFE
      treatment. Control buttermilks, SFE resulting products, and MF and MF-DF SFE and
      all treated retentates products totaled 16 samples (2 types*4 treatments*2
      batches). Eleven trained panelists assessed samples using descriptive analysis.
      Sweet-cream buttermilk was higher in protein and lactose, whereas the WBM had
      similar total protein, mainly beta-LG and alpha-LA but very low lactose. The
      resulting samples in order of concentration for fat and lactose were control
      samples>SFE treated>MF treated>DF=MF-SFE and DF-SFE. Sodium dodecyl sulfate-PAGE
      protein profiling showed negligible casein for WBM versus CBM and less whey
      proteins for CBM versus WBM, as expected. Whey buttermilk was more yellow, salty,
      sour, and rancid than CBM. Regarding the treatments, significant differences were
      obtained on homogeneity, opacity, rancid odor, cardboard and sour flavors, sweet
      and salty tastes, viscosity, and mouthcoating, where SFE-treated samples showed
      lowest rancid odor and cardboard flavor.

PMID- 25864058
TI  - Effects of forage type and extruded linseed supplementation on methane production
      and milk fatty acid composition of lactating dairy cows.
AB  - Replacing dietary grass silage (GS) with maize silage (MS) and dietary fat
      supplements may reduce milk concentration of specific saturated fatty acids (SFA)
      and can reduce methane production by dairy cows. The present study investigated
      the effect of feeding an extruded linseed supplement on milk fatty acid (FA)
      composition and methane production of lactating dairy cows, and whether basal
      forage type, in diets formulated for similar neutral detergent fiber and starch,
      altered the response to the extruded linseed supplement. Four mid-lactation
      Holstein-Friesian cows were fed diets as total mixed rations, containing either
      high proportions of MS or GS, both with or without extruded linseed supplement,
      in a 4*4 Latin square design experiment with 28-d periods. Diets contained 500 g
      of forage/kg of dry matter (DM) containing MS and GS in proportions (DM basis) of
      either 75:25 or 25:75 for high MS or high GS diets, respectively. Extruded
      linseed supplement (275 g/kg ether extract, DM basis) was included in treatment
      diets at 50 g/kg of DM. Milk yields, DM intake, milk composition, and methane
      production were measured at the end of each experimental period when cows were
      housed in respiration chambers. Whereas DM intake was higher for the MS-based
      diet, forage type and extruded linseed had no significant effect on milk yield,
      milk fat, protein, or lactose concentration, methane production, or methane per
      kilogram of DM intake or milk yield. Total milk fat SFA concentrations were lower
      with MS compared with GS-based diets (65.4 vs. 68.4 g/100 g of FA, respectively)
      and with extruded linseed compared with no extruded linseed (65.2 vs. 68.6 g/100
      g of FA, respectively), and these effects were additive. Concentrations of total
      trans FA were higher with MS compared with GS-based diets (7.0 vs. 5.4 g/100 g of
      FA, respectively) and when extruded linseed was fed (6.8 vs. 5. 6g/100 g of FA,
      respectively). Total n-3 FA were higher when extruded linseed was fed compared
      with no extruded linseed (1.2 vs. 0.8 g/100 g of FA, respectively), whereas total
      n-6 polyunsaturated FA were higher when feeding MS compared with GS (2.5 vs. 2.1
      g/100 g of FA, respectively). Feeding extruded linseed and MS both provided
      potentially beneficial decreases in SFA concentration of milk, and no significant
      interactions were found between extruded linseed supplementation and forage type.
      However, both MS and extruded linseed increased trans FA concentration in milk
      fat. Neither MS nor extruded linseed had significant effects on methane
      production or yield, but the amounts of supplemental lipid provided by extruded
      linseed were relatively small.

PMID- 25864059
TI  - Diet and exercise interventions for preventing gestational diabetes mellitus.
AB  - BACKGROUND: Gestational diabetes mellitus (GDM) is associated with a wide range
      of adverse health consequences for women and their babies in the short and long
      term. With an increasing prevalence of GDM worldwide, there is an urgent need to
      assess strategies for GDM prevention, such as combined diet and exercise
      interventions. OBJECTIVES: To assess the effects of combined diet and exercise
      interventions for preventing GDM and associated adverse health consequences for
      women and their babies. SEARCH METHODS: We searched the Cochrane Pregnancy and
      Childbirth Group's Trials Register (11 February 2014) and reference lists of
      retrieved studies. We updated the search in February 2015 but these results have
      not yet been incorporated and are awaiting classification. SELECTION CRITERIA:
      Randomised controlled trials (RCTs) and cluster-RCTs assessing the effects of
      interventions that included diet and exercise components. We included studies
      where combined diet and exercise interventions were compared with no intervention
      (i.e. standard care).We planned to also compare diet and exercise interventions
      with alternative diet and/or exercise interventions but no trials were identified
      for this comparison. DATA COLLECTION AND ANALYSIS: Two review authors
      independently assessed study eligibility, extracted data and assessed the risk of
      bias of the included studies. Data were checked for accuracy. MAIN RESULTS: We
      included 13 randomised controlled trials (involving 4983 women and their babies).
      We assessed the included trials as being of moderate risk of bias overall.When
      comparing women receiving a diet and exercise intervention with those receiving
      no intervention, there was no clear difference in the risk of developing GDM
      (average risk ratio (RR) 0.92, 95% confidence interval (CI) 0.68 to 1.23; 11
      trials, 3744 women), caesarean section (RR 0.92, 95% CI 0.83 to 1.01; seven
      trials, 3246 women), or large-for-gestational age (RR 0.90, 95% CI 0.77 to 1.05;
      2950 infants). Only one trial reported on perinatal mortality, and found no clear
      difference in the risk of stillbirth (RR 0.99, 95% CI 0.29 to 3.42; 2202 fetuses)
      or neonatal death (RR 0.99, 95% CI 0.06 to 15.85; 2202 neonates).Very few
      differences were shown between groups for the review's secondary outcomes,
      including for induction of labour, perineal trauma, pre-eclampsia, postpartum
      haemorrhage and infection, macrosomia, birthweight, small-for-gestational age,
      ponderal index, neonatal hypoglycaemia requiring treatment, hyperbilirubinaemia
      requiring treatment, shoulder dystocia, bone fracture or nerve palsy. Women
      receiving a combined diet and exercise intervention were, however, found to have
      a reduced risk of preterm birth compared with women receiving no intervention (RR
      0.71, 95% CI 0.55 to 0.93; five trials, 2713 women).A trend towards reduced
      weight gain during pregnancy was shown for women receiving the combined diet and
      exercise intervention (mean difference (MD) -0.76 kg, 95% CI -1.55 to 0.03; eight
      trials, 2707 women; P = 0.06, random-effects); but no clear difference in
      postnatal weight retention was observed overall.In relation to adherence to the
      interventions, a number of trials that reported on behaviour modifications showed
      benefits in diet- (5/8 trials) and physical activity- (4/8 trials) related
      behaviours for women receiving the combined diet and exercise intervention,
      compared with women receiving no intervention; however there was notable
      variation across trials in outcomes measured and results observed. Only two
      trials reported on well-being and quality of life of women, and did not observe
      differences between groups for these outcomes.Very few trials reported on
      outcomes relating to the use of health services, although one trial suggested a
      reduced length of antenatal hospital stay for women receiving a combined diet and
      exercise intervention (MD -0.27 days, 95% CI -0.49 to -0.05; 2153 women).No
      information was available on outcomes for the infant as a child or adult, or for
      most longer-term outcomes for the mother. AUTHORS' CONCLUSIONS: There are
      limitations associated with the available RCT evidence on the effects of combined
      diet and exercise interventions during pregnancy for preventing GDM. Results from
      13 RCTs (of moderate quality) suggest no clear difference in the risk of
      developing GDM for women receiving a combined diet and exercise intervention
      compared with women receiving no intervention. However, the ability to draw firm
      conclusions was limited by variations in the quality of trials, characteristics
      of the interventions and populations assessed, and outcome definitions between
      trials.Based on the data currently available, conclusive evidence is not
      available to guide practice. Further large, well-designed RCTs, addressing the
      limitations of previous studies, are needed to assess the effects of combined
      interventions on preventing GDM and other relevant pregnancy outcomes including
      caesarean birth, large-for-gestational age and perinatal mortality. Health
      service utilisation and costs, and longer-term outcomes for mothers and their
      babies should be included. We identified another 16 trials which are ongoing and
      we will consider these for inclusion in the next update of this review.

PMID- 25864060
TI  - Improving communication with multiple sclerosis patients.

PMID- 25864061
TI  - Focal brainstem gliomas. Advances in intra-operative management.
AB  - Improved neuronavigation guidance as well as intraoperative imaging and
      neurophysiologic monitoring technologies have enhanced the ability of
      neurosurgeons to resect focal brainstem gliomas. In contrast, diffuse brainstem
      gliomas are considered to be inoperable lesions. This article is a continuation
      of an article that discussed brainstem glioma diagnostics, imaging, and
      classification. Here, we address open surgical treatment of and approaches to
      focal, dorsally exophytic, and cervicomedullary brainstem gliomas. Intraoperative
      neuronavigation, intraoperative neurophysiologic monitoring, as well as
      intraoperative imaging are discussed as adjunctive measures to help render these
      procedures safer, more acute, and closer to achieving surgical goals. 

PMID- 25864062
TI  - Update on neuropathic pain treatment for trigeminal neuralgia. The
      pharmacological and surgical options.
AB  - Trigeminal neuralgia is a syndrome of unilateral, paroxysmal, stabbing facial
      pain, originating from the trigeminal nerve. Careful history of typical symptoms
      is crucial for diagnosis. Most cases are caused by vascular compression of the
      trigeminal root adjacent to the pons leading to focal demyelination and ephaptic
      axonal transmission. Brain imaging is required to exclude secondary causes. Many
      medical and surgical treatments are available. Most patients respond well to
      pharmacotherapy; carbamazepine and oxcarbazepine are first line therapy, while
      lamotrigine and baclofen are considered second line treatments. Other drugs such
      as topiramate, levetiracetam, gabapentin, pregabalin, and botulinum toxin-A are
      alternative treatments. Surgical options are available if medications are no
      longer effective or tolerated. Microvascular decompression, gamma knife
      radiosurgery, and percutaneous rhizotomies are most promising surgical
      alternatives. This paper reviews the medical and surgical therapeutic options for
      the treatment of trigeminal neuralgia, based on available evidence and
      guidelines. 

PMID- 25864063
TI  - Telmisartan inhibits hyperalgesia and inflammatory progression in a diabetic
      neuropathic pain model of Wistar rats.
AB  - OBJECTIVE: To evaluate the potential therapeutic value of telmisartan (TMT)
      against diabetic neuropathy (DN) and associated pain in Wistar rats. METHODS:
      Peripheral DN was induced by a single intraperitoneal streptozotocin injection
      (55 mg/kg), and 3 weeks later TMT treatment was started (5 and 10 mg/kg/day), and
      continued for 4 weeks. Mechanical nociceptive threshold, motor coordination, and
      thermal nociceptive threshold tests were performed before and after TMT
      treatment. In serum, glucose, pro-inflammatory cytokines including tumor necrosis
      factor-alpha, interleukin-1beta, and interleukin-6 were assessed. Nerve growth
      factor (NGF) levels and histopathological changes were estimated in the sciatic
      nerve. This study was conducted at the Experimental Animal Care Center,
      Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh,
      Kingdom of Saudi Arabia between January 2013 and May 2014. RESULTS: We observed a
      significant reduction in mechanical nociceptive threshold, motor coordination,
      and thermal nociceptive threshold in diabetic animals. The TMT treatment
      significantly enhanced the reduced mechanical nociceptive threshold. The
      untreated diabetic animals revealed a significant decrease in sciatic NGF, which
      was markedly attenuated by TMT. The elevated serum levels of cytokines in
      diabetic animals were inhibited by the TMT treatments. Histopathological
      evaluation showed obvious nerve degeneration in the diabetic group that was
      eliminated in the TMT treated diabetic groups. CONCLUSION: Telmisartan has a
      potential neuro-protective effect on peripheral DN; this is mediated through its
      anti-inflammatory effects and its dual properties as an angiotensin receptor
      blocker, and a partial peroxisome proliferator activator receptor-gamma ligand.

PMID- 25864064
TI  - Potential neuroprotective effect of Anakinra in spinal cord injury in an in vivo
      experimental animal model.
AB  - OBJECTIVE: To evaluate the therapeutic effects of inhibiting interleukin-1 beta
      (IL-1 beta) in vivo using Anakinra in an experimental model of spinal cord injury
      (SCI). METHODS: All experimental procedures were performed in the animal
      laboratory of Ankara Education and Research Hospital, Ankara, Turkey between
      August 2012 and May 2014. The SCI was induced by applying vascular clips to the
      dura via a 4-level T5-T8 laminectomy. Fifty-four rats were randomized into the
      following groups: controls (n = 18), SCI + saline (n = 18), and SCI + Anakinra (n
      = 18). Spinal cord samples were obtained from animals in both SCI groups at one,
      6, and 24 hours after surgery (n = 6 for each time point). Spinal cord tissue and
      serum were extracted, and the levels of IL-1 beta, malondialdehyde, glutathione
      peroxidase, superoxide dismutase, and catalase were analyzed. Furthermore,
      histopathological evaluation of the tissues was performed. RESULTS: The SCI in
      rats caused severe injury characterized by edema, neutrophil infiltration, and
      cytokine production followed by recruitment of other inflammatory cells, lipid
      peroxidation, and increased oxidative stress. After SCI, tissue and serum IL-1
      beta levels were significantly increased, but were significantly decreased by
      Anakinra administration. Following trauma, glutathione peroxidase, superoxide
      dismutase, and catalase levels were decreased; however, Anakinra increased the
      activity of these antioxidant enzymes. Malondialdehyde levels were increased
      after trauma, but were unaffected by Anakinra. Histopathological analysis showed
      that Anakinra effectively protected the spinal cord tissue from injury.
      CONCLUSION: Treatment with Anakinra reduces inflammation and other tissue injury
      events associated with SCI.

PMID- 25864065
TI  - Assessment of pain. Knowledge, attitudes, and practices of health care providers
      in Almadinah Almunawwarah, Saudi Arabia.
AB  - OBJECTIVE: To present data on knowledge and attitudes toward pain assessment
      among health care providers in Almadinah Almunawwarah, Saudi Arabia. METHODS:
      This exploratory study required at least 100 participants to attain an effect
      size of 0.2 or larger. A convenience sample was recruited from the major
      hospitals in Almadinah Almunawwarah, Saudi Arabia; King Fahad Hospital, Ohud
      Hospital, Alansar Hospital, Almeqat Hospital, and the Maternity Hospital. Data
      collection occurred between January and April 2014. Knowledge of pain assessment
      was examined by administering the Knowledge and Attitudes Survey Regarding Pain.
      RESULTS: Data from 105 participants was collected. Seventy-three participants
      scored 44% or below (69.5%), and 32 participants scored 45% and above (30.5%).
      Additionally, only 6 participants (5.7%) scored above 60%. There were significant
      differences between male and female scores (p=0.05), physicians' and nurses'
      scores (p=0.001), and level of education (p=0.009). There were no significant
      differences in the passing scores across means of nationality, the department
      where participants worked, years of experience, and age of participants.
      CONCLUSION: There is a deficit in pain assessment knowledge, and pain management
      in the study group. Continuous education on pain assessment is required to
      increase the health care providers' knowledge, and enhance their practices
      regarding pain assessment and treatment.

PMID- 25864066
TI  - Systematic review of the epidemiology of attention deficit hyperactivity disorder
      in Arab countries.
AB  - OBJECTIVE: To assess the epidemiology of attention deficit hyperactivity disorder
      (ADHD) in Arab countries, and identify gaps for future research. METHODS: We
      searched PubMed from July 1978 to July 2014 and reviewed local journals with
      cross-referencing. The keywords we used were ADHD, diagnosis, prevalence,
      incidence, factor, diagnosis, rate, risk, and each of the names of the 22 Arab
      countries (Jordan, Egypt, Lebanon, Saudi Arabia, and so on). Studies were
      eligible for inclusion if they investigated the epidemiology of ADHD in any Arab
      country, and were published in English. The search was conducted from 2nd to 5th
      August 2014 in King Saud Bin Abdulaziz University for Health Sciences, Riyadh,
      Saudi Arabia. RESULTS: A total of 22 articles were included in the review. Twenty
      studies were cross-sectional and found the prevalence of ADHD ranged between 1.3
      16%, prevalence of hyperactive type ADHD between 1.4-7.8%, and the prevalence of
      inattention type between 2.1-2.7%. Only 2 case-control studies investigated
      potential risk factors. Evidence extracted from these studies shows a significant
      association between ADHD and male gender, previous psychiatric illness in the
      family, vitamin D deficiency, poor school performance, sleep problems, and
      nocturnal enuresis. CONCLUSION: The prevalence of ADHD in Arab countries is
      comparable to reports in North America, Africa, and other countries of the Middle
      East. Longitudinal studies are needed to investigate the prognosis and
      determinants of this condition in the Arab world.

PMID- 25864067
TI  - Information needs, care difficulties, and coping strategies in families of people
      with mental illness.
AB  - OBJECTIVE: To determine information needs, care difficulties, and coping
      mechanisms of family members of people with mental illness. METHODS: In this
      descriptive cross-sectional study, the study sample consisted of the families of
      134 patients who were treated in the Psychiatric Unit of Cumhuriyet University
      Training and Research Hospital in Sivas, Turkey between January and May 2011.
      Data was collected by a questionnaire and analysed descriptively, and by chi
      square testing. RESULTS: It was determined that 79.1% of family members were
      knowledgeable of the patients' illness. It was found that they experienced
      difficulties in communicating with the patient, and in ensuring drug compliance
      and anger management and that they used psychological and social coping
      strategies. CONCLUSION: Our results indicate that access to medical information
      on its own is not sufficient for carers of people with mental illness, and the
      necessity of developing positive attitudes when dealing with the illness and its
      symptoms. We recommend that nurses and other health professionals offer long term
      support and consultation programs to family members.

PMID- 25864068
TI  - Thought suppression predicts task switching deficits in patients with frontal
      lobe epilepsy.
AB  - OBJECTIVE: To examine the relationship between task switching and thought
      suppression in connection with frontal lobe epilepsy (FLE). METHODS: This
      experimental study included 30 patients with FLE admitted to the Services and
      Jinnah Hospital, Lahore, Pakistan between February and November 2013, and 30
      healthy individuals from the local community. Participants performed a task
      switching experiment where they switched between emotion and age categorizations
      among faces. In addition, they completed a thought suppression questionnaire.
      RESULTS: There were 3 important results: (i) Patients with FLE showed weaker task
      switching abilities than healthy individuals. This result is attributed toward
      executive dysfunctions in patients with FLE. (ii) Contrary to the control group,
      patients with FLE showed larger switch cost for the age than the emotion
      categorization. This result can be seen in the context of social cognition
      deficits and poor inhibitory control in patients with FLE. In addition, larger
      switch costs reflected a binding effect with facial emotion as compared to age.
      The integration might represent emotion as an intrusive facial dimension that
      interrupted task switching performance. (iii) Patients with FLE had more
      recurrent suppression of thoughts than controls. Thought suppression was a
      significant predictor for switch costs. High scores on thought suppression were
      correlated with task switching deficits. CONCLUSION: The results suggest that
      thought suppression causes significant cognitive decline.

PMID- 25864069
TI  - Management of infiltrating spinal epidural angiolipoma.
AB  - Angiolipomas of the spine are rare benign tumors commonly presenting with
      compressive myelopathy. The present report describes a case of spinal angiolipoma
      with thoracic mediastinal extension in a 50-year-old woman. She presented with a
      long-standing history of mid-back pain with progressive lower extremities
      weakness. An MRI showed a heterogeneously enhancing mass located in the posterior
      epidural space of the thoracic spine with mediastinal extension.
      Histopathological examination demonstrated features consistent with spinal
      angiolipoma. This report emphasizes the diagnosis and therapeutic management
      options of infiltrating spinal angiolipomas. 

PMID- 25864070
TI  - Tremor onset with acute frontal infarct and disappearance with the second stroke.
AB  - Ischemic stroke associated movement disorders can be seen as the first sign of a
      stroke or as a delayed onset development. Tremor after a stroke is a rare finding
      among movement disorders. In addition to reports of tremor caused by cerebral
      infarction of varied locations, data on the disappearance of existing tremor
      following infarction is also available. In this report, we present a case with
      acute tremor in the contralateral hand following frontal cortical infarction, and
      disappearance of the tremor after the second infarction comprising large areas in
      the same hemisphere. 

PMID- 25864071
TI  - Another cause of headache after epidural injection.
AB  - Headache is a potential complication of epidural injection. We report a patient
      who developed headache 5 days after a lumbar epidural steroid injection, which
      was not related to the epidural procedure, but caused by Duloxetine induced
      hyponatremia. Antidepressant drug induced headache should be considered in the
      differential diagnosis of post dural puncture headache. 

PMID- 25864072
TI  - Brain abscess caused by Citrobacter koseri infection in an adult.
AB  - Citrobacter koseri is a gram-negative bacillus that causes mostly meningitis and
      brain abscesses in neonates and infants. However, brain abscess caused by
      Citrobacter koseri infection in an adult is extremely rare, and only 2 cases have
      been described. Here, we reported a 73-year-old male presenting with a 3-week
      headache. A history of diabetes mellitus was noted. The images revealed a brain
      abscess in the left frontal lobe and pus culture confirmed the growth of
      Citrobacter koseri. The clinical symptoms improved completely postoperatively. 

PMID- 25864073
TI  - Clinical and genetic features of anoctaminopathy in Saudi Arabia.
AB  - OBJECTIVE: Characterization of the phenotypic, pathological, radiological, and
      genetic findings in 2 Saudi Arabian families with anoctaminopathies, and limb
      girdle muscular dystrophy type 2L (LGMD2L). METHODS: Over a 2-year period from
      December 2010 to January 2013, the clinical presentations were analyzed and all
      genes responsible for limb girdle muscular dystrophy (LGMD) were screened in
      families seen at King Faisal Specialist Hospital and Research Centre, a tertiary
      care hospital in Riyadh, Saudi Arabia. Out of 66 families with LGMD, we
      identified 2 families (3.1%) with anoctaminopathy, ANO5 muscular dystrophy.
      RESULTS: In the first case, a man presented with asymmetrical calves' muscles
      weakness and atrophy, which was first noted at age 39. The creatinine kinase (CK)
      level was >20x normal, muscle biopsy showed necrotizing myopathic changes, and an
      MRI of the legs showed fatty-tissue replacement to muscle tissue with volume loss
      involving the gastrocnemius and soleus muscles in an asymmetrical fashion.
      Minimal disease progression was noted over 18 years of follow up. Exercise
      induced recurrent rhabdomyolysis was noted over the last 2 years. A novel ANO5
      gene mutation (Arg58Trp) was found. In the second family, a male presented at the
      age of 41 with asymptomatic hyperCkemia and intermittent dyspnea. Over 10 years
      follow up, he became disabled with muscle cramps, rhabdomyolysis, my oglobinurea,
      and difficulty ambulating. Muscle biopsy showed necrotizing myopathy and
      perivascular and interstitial amyloid deposit in skeletal muscle. A homozygous
      deletion of 11.9 Kb encompassing exon 13 to exon 17 was found in the ANO5 gene.
      Full cardiac investigations were normal in both patients. CONCLUSION: The
      prevalence of LGMD2L is approximately 3.1% in a Saudi Arabian native LGMD cohort.
      Slowly progressive, late onset, and asymmetrical weakness was the salient
      features in these 2 families. The genetic findings were novel and will add to the
      spectrum of ANO5 known mutations.

PMID- 25864074
TI  - Factors associated with poor outcomes of hospitalized myasthenia gravis.

PMID- 25864075
TI  - Cerebral angiography. Unusual connection and disconnection.
AB  - A 61-year-old woman underwent MRI scan of brain (Figure 1A), followed by
      conventional angiography (Figures 1B & 1C) and magnetic resonance cerebral
      angiography (Figure 1D, conventional angiography was performed for more specific
      details regarding the findings of the initial MR cerebral angiography) as part of
      the ischemic stroke work-up for recurrent episodes of right hemiparesis and
      expressive aphasia. 

PMID- 25864076
TI  - Fasting and other mild stresses with hormetic effects in Drosophila melanogaster
      can additively increase resistance to cold.
AB  - Mild stresses can have various positive effects in animal models and human
      beings. Previous studies have shown that fasting, i.e. a short starvation period
      with water ad lib, increases resistance to a severe cold stress in flies
      (percentage of survivors 3 days after being kept at 0  degrees C). Only a few
      studies have combined two mild stresses with hormetic effects in an attempt to
      obtain additive effects. Fasting was combined in the same flies with either a
      hypergravity, cold or heat stress and resistance to cold was observed. When each
      mild stress had positive effects on this trait (fasting, cold, and hypergravity
      in males only), their combination had additive effects. However, when one of the
      mild stresses had no positive effect or even a negative effect (heat), combining
      it with fasting did not increase the positive effect of fasting or even decreased
      it. 

PMID- 25864077
TI  - Occupants' satisfaction toward building environmental quality: structural
      equation modeling approach.
AB  - It is accepted that occupants who are more satisfied with their workplace's
      building internal environment are more productive. The main objective of the
      study was to measure the occupants' level of satisfaction and the perceived
      importance of the design or refurbishment on office conditions. The study also
      attempted to determine the factors affecting the occupants' satisfaction with
      their building or office conditions. Post-occupancy evaluations were conducted
      using a structured questionnaire developed by the Built Environment Research
      Group at the University of Manchester, UK. Our questionnaires incorporate 22
      factors relating to the internal environment and rate these in terms of "user
      satisfaction" and "degree of importance." The questions were modified to reflect
      the specific setting of the study and take into consideration the local
      conditions and climate in Malaysia. The overall mean satisfaction of the
      occupants toward their office environment was 5.35. The results were measured by
      a single item of overall liking of office conditions in general. Occupants were
      more satisfied with their state of health in the workplace, but they were
      extremely dissatisfied with the distance away from a window. The factor analysis
      divided the variables into three groups, namely intrusion, air quality, and
      office appearance. Structural equation modeling (SEM) was then used to determine
      which factor had the most significant influence on occupants' satisfaction:
      appearance. The findings from the study suggest that continuous improvement in
      aspects of the building's appearance needs to be supported with effective and
      comprehensive maintenance to sustain the occupants' satisfaction. 

PMID- 25864078
TI  - The impacts of long-term intensive agriculture on the Vertisol properties in a
      calcareous region.
AB  - Morphological, physicochemical, and mineralogical properties of Vertisols
      (Chromic Calcixererts, Typic Haploxererts, and Typic Calcixererts) influenced
      under farming practices and adjoining uncultivated soils were investigated in
      order to contribute to the understanding of changes derived by intensive
      cultivation (over five decades). The study revealed that A-horizon thickness
      enhanced from 20 cm in the uncultivated soil to 30 cm in the cultivated soil for
      Typic Haploxererts and Typic Calcixererts. Under cropping, calcium carbonate
      contents decreased (a drop of 10 to 53%) reflecting accelerated leaching and/or
      erosion by cultivation. For most of the studied soils, a pronounced depletion was
      recorded at values of soil organic carbon (23-64%), soluble cations (4-96%), and
      exchangeable cations (9-42%) after cropping. A considerable positive change in
      soil quality was observed with cultivation as recorded by a declining trend in
      soil electrical conductivity (a drop of 12 to 17%) and exchangeable sodium
      percentage (a drop of 9 to 12%). On average, the concentration of free and
      crystalline Fe oxides progressively increased for Chromic Calcixererts and Typic
      Calcixererts following intensive cultivation. Cropping operations considerably
      promoted the alteration of illite and chlorite minerals into expandable minerals
      linked with changes in soil physicochemical properties mainly the increase in
      cation exchange capacity. Land productivity index (LPI), evaluated based on
      parametric approach, suggested that Chromic Calcixererts and Typic Haploxererts
      highlighted a decreasing trend in LPI values (a drop of 5 to 7%) while Typic
      Calcixererts manifested an increasing pattern in the index (a rise of 13%) with
      long-term intensive cropping.

PMID- 25864079
TI  - Estimation of human health risk associated with the consumption of pesticide
      contaminated vegetables from Kumasi, Ghana.
AB  - Analysis of pesticides consisting of 12 organophosphates (OPs), 10
      organochlorines (OCs), and 6 pyrethroids in vegetables from Kumasi was conducted.
      Vegetable samples comprising 20 each of eggplants, okra, and tomatoes were
      analyzed. The method involves solvent extraction of pesticide residues followed
      by cleanup using silica gel. Residue analysis was carried out using a GC equipped
      with pulsed flame photometric detector for OP residues and electron capture
      detector for OC and pyrethroid residues. The results revealed that methamidophos
      exceeded the maximum residue limits (MRLs) in all vegetable commodities. Levels
      of malathion and dimethoate also exceeded the MRLs in eggplant and tomato
      samples. Endrin, alpha-endosulfan, gamma-hexachlorocyclohexane (HCH), gamma
      chlordane, and heptachlor exceeded their MRLs in okra samples whereas
      methoxychlor, allethrin, and deltamethrin exceeded in eggplant samples. Health
      risk estimation revealed that dimethoate in tomato and endrin, heptachlor, gamma
      HCH, and gamma-chlordane in okra could not pose potential toxicity to the
      consumer. The combined risk index showed no health risk to consumers due to
      intake of pyrethroid OC and OP residue on these vegetables. The overall risk
      index for combined pesticides due to consumption of all the vegetables was higher
      than 1, which signifies potential health risk to consumers. OPs were the major
      risk contributor for both eggplant and tomatoes which accounted for 87.78 and
      95.84%, respectively, of the combined risk of pesticides in the vegetables.
      However, OC with 97.94% of the combined risk index was the major risk contributor
      for the okra. The carcinogenic risk of the OCs in okra was of no concern since
      their carcinogenic rates were below the acceptable risk level.

PMID- 25864080
TI  - Dissipation pattern and risk assessment of flubendiamide on chili at different
      agro-climatic conditions in India.
AB  - Dissipation pattern and risk assessment of flubendiamide and its metabolite
      (desiodo flubendiamide) on chili were studied at four different agro-climatic
      locations of India at the standard and double dose at 60 and 120 g a.i. ha(-1) at
      10 days interval. Quantification of residues was done on a high-performance
      liquid chromatograph (HPLC) with a photo diode array detector. The limit of
      quantification (LOQ) of this method was found to be 0.01 mg kg(-1) while limit of
      detection (LOD) being 0.003 mg kg(-1). Residues of flubendiamide were found to be
      below the determination limit in 15 days at both the dosages in all locations.
      Half-life of flubendiamide when applied at 60 and 120 g a.i. ha(-1) ranged from
      0.85 to 1.80 and from 0.95 to 2.79 days, respectively. On the basis of data
      generated under the All India Network Project on Pesticide Residues, a preharvest
      interval (PHI) of 1 day has been recommended and the flubendiamide 480 SC has
      been registered for use on chili in India by the Central Insecticide Board and
      Registration Committee, Ministry of Agriculture, Government of India. The maximum
      residue limit (MRL) of flubendiamide on chili has been fixed by the Food Safety
      Standard Authority of India, Ministry of Health and Family Welfare, Government of
      India, as 0.02 MUg g(-1) after its risk assessment. 

PMID- 25864081
TI  - Freshwater diatoms as environmental indicators: evaluating the effects of
      eutrophication using species morphology and biological indices.
AB  - Anthropogenic eutrophication is a major form of perturbation in freshwaters, and
      several approaches aim to recognise its effects on lake ecosystems. We compared
      the responses of diatom species morphology, diversity indices and diatom indices
      to total phosphorus, total nitrogen and distance from a point stressor causing
      eutrophication in a large lake. We specifically examined the degree to which
      extent nutrients and distance to the stressor affect variation in the values of
      various biological indices and diatom valve size. In addition, special attention
      was given to the adequate repetition of diatom valve width measurements in the
      context of environmental assessment. Our results showed that diatom valve width
      was a better indicator of nutrient concentrations than any of the diatom and
      diversity indices examined. However, the results varied between the two study
      transects, suggesting that the diatom-based variables not only respond to
      nutrients but also to other environmental factors (e.g. shoreline morphology). We
      also found that when using the method based on diatom morphology, one should
      measure more valves than has been originally suggested to provide a more reliable
      picture of response to eutrophication. We argue that diatom morphology could be
      considered as an additional environmental assessment tool, because it may
      complement the information provided by the traditional diatom indices. Diatom
      valve width may also be more sensitive to early phases of the eutrophication
      process and its effects on freshwater ecosystems than various diatom indices that
      were developed in regional contexts with wide ranges in nutrient levels. 

PMID- 25864082
TI  - Temporal variation of phytoplankton growth and grazing loss in the west coast of
      Peninsular Malaysia.
AB  - Phytoplankton growth (MU) and grazing loss (g) rates were measured monthly by the
      Landry-Hassett dilution method over a 2-year period at both estuarine (Klang) and
      coastal water (Port Dickson) systems along the Straits of Malacca. Chlorophyll a
      (Chl a) concentration ranged from 0.20 to 4.47 MUg L(-1) at Klang except on two
      occasions when Chl a spiked above 10 MUg L(-1). In contrast, Chl a concentrations
      were relatively stable at Port Dickson (0.14 to 2.76 MUg L(-1)). From the rate
      measurements, MU was higher (t = 2.01, df = 43, p < 0.05) at Klang (0.30 to 2.26
      day(-1)) than at Port Dickson (0.18 to 1.66 day(-1)), but g was not significantly
      different (p > 0.80). g ranged from 0.30 to 1.50 and 0.21 to 1.51 day(-1) at
      Klang and Port Dickson, respectively. In this study, grazing loss was coupled to
      phytoplankton growth, and the ratio of g/MU or grazing pressure which estimates
      the proportion of primary production grazed was 50% at Klang and lower than at
      Port Dickson (68%; t = 2.213, df = 36, p < 0.05). We found that the higher growth
      rates in a eutrophic system, i.e., Klang, were not matched by higher grazing
      loss, and this may have implications for the biogeochemical cycling in coastal
      waters.

PMID- 25864083
TI  - Margaret Gladys Smith, mother of cytomegalovirus: 60th anniversary of
      cytomegalovirus isolation.

PMID- 25864084
TI  - Malnutrition According to Mini Nutritional Assessment Is Associated With Severe
      Functional Impairment in Geriatric Patients Before and up to 6 Months After Hip
      Fracture.
AB  - OBJECTIVES: Hip fractures (HFs) in old age frequently cause severe functional
      impairment and deteriorating autonomy in everyday life. Many older patients with
      HFs are malnourished or at risk of malnutrition. In this study, we examined the
      relationship between nutritional status of geriatric patients before HF and their
      functional and clinical course up to 6 months after hospital discharge. DESIGN:
      Observational study with follow-up after 6 months. SETTING: Four wards of the
      department of trauma and orthopedic surgery of a large urban maximum care
      hospital (Klinikum Nurnberg, Nuremberg, Germany). PARTICIPANTS: Geriatric
      patients aged >=75 years with surgically repaired proximal femoral fracture.
      MEASUREMENTS: Prefracture nutritional status was determined by Mini Nutritional
      Assessment (MNA). Comorbidities and complications during hospital stay were
      obtained from medical documentation. Functional status before HF,
      postoperatively, at hospital discharge, and 6 months later was assessed by
      Barthel Index for activities of daily living (ADL) and patients' mobility level
      and related to MNA categories. Associations were evaluated using chi(2), Fisher
      exact, Kruskal-Wallis, Mann-Whitney-U, Jonckheere-Terpstra, and Cochrane-Armitage
      tests as appropriate, as well as analysis of covariance with repeated measures.
      RESULTS: Of 97 included patients, 17% were malnourished and 38% at risk of
      malnutrition before HF. Participants with (risk of) malnutrition were equally
      mobile but more dependent in ADL prior to HF than well-nourished patients (P <
      .001). Independent of nutritional status, after 6 months 68% of participants had
      not regained their prefracture level of independence in ADL. According to
      analysis of covariance, the ADL development over time until follow-up 6 months
      after hospital discharge did not depend on nutritional status. However, at follow
      up malnourished patients more often suffered from remaining losses in ADL >=25%
      of initial Barthel Index points (P = .033) and less often had regained their
      prefracture mobility level (P = .020) than well-nourished patients. Clinical
      course did not differ significantly between the groups with different nutritional
      status. CONCLUSIONS: In this study with geriatric HF patients from all functional
      and cognitive levels, worse prefracture nutritional status was associated with
      worse functional status and more frequent remaining functional loss, whereas the
      trajectory of ADL recovery and clinical course did not differ significantly.
      Further studies with sufficient statistical power are needed to substantiate
      these inconclusive results. In order to clarify the association of nutritional
      status with functional and clinical course in geriatric patients after HF, they
      should preferably focus on the role of nutritional management during the hospital
      stay.

PMID- 25864085
TI  - Ancestral Insertions and Expansions of rRNA do not Support an Origin of the
      Ribosome in Its Peptidyl Transferase Center.
AB  - Phylogenetic reconstruction of ribosomal history suggests that the
      ribonucleoprotein complex originated in structures supporting RNA decoding and
      ribosomal mechanics. A recent study of accretion of ancestral expansion segments
      of rRNA, however, contends that the large subunit of the ribosome originated in
      its peptidyl transferase center (PTC). Here I re-analyze the rRNA insertion data
      that supports this claim. Analysis of a crucial three-way junction connecting the
      long-helical coaxial branch that supports the PTC to the L1 stalk and its
      translocation functions reveals an incorrect branch-to-trunk insertion assignment
      that is in conflict with the PTC-centered accretion model. Instead, the insertion
      supports the ancestral origin of translocation. Similarly, an insertion linking a
      terminal coaxial trunk that holds the L7-12 stalk and its GTPase center to a
      seven-way junction of the molecule again questions the early origin of the PTC.
      Unwarranted assumptions, dismissals of conflicting data, structural insertion
      ambiguities, and lack of phylogenetic information compromise the construction of
      an unequivocal insertion-based model of macromolecular accretion. Results prompt
      integration of phylogenetic and structure-based models to address RNA junction
      growth and evolutionary constraints acting on ribosomal structure. 

PMID- 25864086
TI  - Field Ultrasound Evaluation of Central Volume Status and Acute Mountain Sickness.
AB  - OBJECTIVE: To investigate whether ultrasonography can be used for field volume
      status assessment and to determine whether a detectable difference in
      intravascular volume exists in individuals with acute mountain sickness (AMS)
      compared with those without. METHODS: Study was performed at the Himalayan Rescue
      Association Clinic in Manang, Nepal, located on the Annapurna trekking circuit at
      an altitude of 3519 m (11545 feet). A convenience sample was taken from
      individuals trekking over 5 to 8 days from 760 m (2490 feet) to 3519 m (11,545
      feet), comparing asymptomatic trekkers vs those who experienced AMS. Subjects
      were evaluated for AMS based on the Lake Louise AMS Questionnaire (LLS >= 3
      indicates AMS). After medical screening examination, both groups (control, n =
      51; AMS, n = 18) underwent ultrasonography to obtain measurements of inferior
      vena cava collapsibility index (IVC CI) and left ventricular outflow tract
      velocity-time integral (LVOT VTI) before and after a passive leg raise (PLR)
      maneuver. RESULTS: There was no statistically significant difference between
      groups regarding change in heart rate before and after PLR, or IVC CI; however,
      there was a statistically significant greater increase in LVOT VTI after PLR
      maneuver in control group subjects compared with those with AMS (18.96% control
      vs 11.71% AMS; P < .01). CONCLUSIONS: Ultrasonography is a useful tool in the
      assessment of intravascular volume at altitude. In this sample, we found
      ultrasonographic evidence that subjects with AMS have a higher intravascular
      volume than asymptomatic individuals. These data support the hypothesis that
      individuals with AMS have decreased altitude-related diuresis compared with
      asymptomatic individuals.

PMID- 25864087
TI  - Cemented total hip arthroplasty revisions in patients of eighty years and older.
AB  - PURPOSE: It is often a difficult decision whether it is safe to perform revision
      hip surgery in a patient of 80 years and older. Therefore we evaluated the
      results of cemented revisions in these elderly patients. METHODS: Clinical data,
      radiographs and complications of 49 consecutive cup and/or stem revisions in 48
      patients were prospectively collected. The average age of the patients at surgery
      was 84 years (range, 80-92). We performed Kaplan-Meier (KM) analysis and also a
      competing risk (CR) analysis because in this series the presence of a competing
      event (i.e. death) prevents the occurrence of endpoint rerevision. RESULTS:
      Twenty-nine patients (30 hips) died without rerevision during follow-up and their
      data was included. The average follow-up of the 16 surviving patients was eight
      years (range, six to 13). Six re-operations were performed, of which three were
      re-revisions. Eight-year survivorship was 91.6% (95% confidence interval (CI) 76
      97%) for endpoint re-revision for any reason. With the CR analysis we calculated
      that due to the increasing number of competing events, the KM analysis
      overestimates the failure rate with 32% for this endpoint. The average Harris hip
      score improved from 49 to 74. Mortality within three months after surgery was 6%.
      One postoperative fracture occurred and six hips dislocated. CONCLUSION: Cemented
      revisions can provide satisfying results in patient of 80 years and older with
      acceptable survivorship and complication rates.

PMID- 25864088
TI  - Evaluation of transforaminal endoscopic lumbar discectomy in the treatment of
      lumbar disc herniation.
AB  - PURPOSE: The purpose of this study was to evaluate the efficacy of transforaminal
      endoscopic lumbar discectomy (TELD) in the treatment of lumbar disc herniation
      (LDH) and to identify the relationship between TELD efficacy and age. METHODS: A
      total of 207 consecutive LDH patients who had undergone TELD with the THESSYS
      system from January 2013 to September 2014 were divided into two groups on the
      basis of their age, with 108 cases in the <= 45-year-old age group and 99 cases
      in the >45-year-old group. The Oswestry Disability Index (ODI) was used to
      quantify the pain relief. The degree of pain and disability were measured on the
      basis of the visual analog scale (VAS) and the modified MacNab criteria.
      Complications, duration of hospital stay, surgical costs, and operation time were
      recorded and compared between the two groups. Spearman's coefficient of rank
      correlation was used to assess the learning curves for TELD. RESULTS: The mean
      pre-operative and postoperative VAS and ODI scores significantly improved in both
      age <= 45 group and age >45 group, with no significant differences between them.
      In age <=45 group, 56 % had excellent outcomes, 28 % good, 14 % fair, and 3 %
      poor. In the age >45 group, 51 % had excellent outcomes, 20 % good, 25 % fair,
      and 4 % poor. The average lengths of hospital stay for the age <= 45 group and
      age >45 group were 6.8 and 8.4 days, respectively. The mean time to return to
      work or normal activities was ten days for the age <= 45 group and 15 days for
      the age >45 group. The mean operative time for the age <= 45 group was 94 minutes
      and that for age >45 group was 97 minutes. The surgical cost of age <= 45 group
      was 15,480 RMB, which was lower than the 16,381 RMB of age >45 group. A total of
      14 patients in the age <= 45 group and 13 patients in age >45 group used
      analgesic medications. Three and five recurrences were reported in the age <= 45
      group and age >45, respectively. The steep learning curves of operative time
      plotted against the number of surgeries conducted suggest that the TELD technique
      can be mastered quickly in terms of reducing the duration of operation.
      CONCLUSIONS: The efficacy of TELD is relatively good for the selected young and
      elderly patients in this study. Therefore, age is not a predictor of TELD surgery
      related outcomes.

PMID- 25864089
TI  - The outcome of hemiarthroplasty for proximal humeral fractures is dependent on
      the status of the rotator cuff.
AB  - PURPOSE: The purpose of this study was to evaluate clinical and radiological
      outcomes of hemiarthroplasty for proximal humerus fractures. METHODS: Thirty-five
      patients (33 women and two men), average age at the time of surgery of 75.1
      (range, 64-92) years, who underwent hemiarthroplasty for proximal humerus
      fracture or fracture-dislocation of the shoulder were enrolled in this study. The
      Constant score was used for clinical evaluation of outcomes, and X-rays were
      performed after a minimum follow-up period of 12 months postoperatively.
      Parameters for radiological evaluation were as follows: value of acromiohumeral
      interval (AHI), humeral offset, medial and lateral projection, and the existence
      of subacromial spur, a radiolucent zone around humeral stem and an osteolytic
      change of the greater tuberosity. RESULTS: The average follow-up after surgery
      was 45.8 (range, 13-114) months. The average postoperative Constant score was
      76.2 (range, 53-96) points. The mean values of AHI and humeral offset were 8.4
      and 28.3 mm, respectively. A subacromial spur was observed in ten patients, and
      an osteolytic change of the greater tuberosity in seven patients. There was a
      significant correlation between Constant score and values of AHI or humeral
      offset. The Constant score in patients with a subacromial spur or radiolucent
      zone around humeral stem was markedly lower than that in patients without them.
      CONCLUSIONS: The clinical outcome of hemiarthroplasty was influenced by factors
      reflecting function and conditions of the rotator cuff. Anatomical reconstruction
      and bone union of the tuberosities need to ensure clinical success in
      hemiarthroplasty.

PMID- 25864090
TI  - Advances in Science and Biomedical Research on Postpartum Depression do not
      Include Meaningful Numbers of Latinas.

PMID- 25864091
TI  - Reasons for Pacifier Use and Non-Use in African-Americans: Does Knowledge of
      Reduced SIDS Risk Change Parents' Minds?
AB  - To investigate African-American parental reasons for pacifier use or non-use, and
      whether knowledge of the association with decreased SIDS risk changes decisions
      about pacifier use. We conducted focus groups and individual interviews with
      mothers. Grounded theory methodology was used. 83 mothers participated; 72.3 % of
      infants used pacifiers. Reasons for pacifier use included comfort/soothing,
      safety/SIDS, and preference over digit-sucking. Reasons for pacifier non-use
      included infant refusal, fear of attachment, nipple confusion, and germs. Many
      parents were unaware that pacifier use reduces SIDS risk; however, most parents
      of non-users did not think that this knowledge would have changed their decision.
      Reasons included skepticism about the pacifier-SIDS link. Many reasons underlie
      African-American parental decisions about pacifier use. Providers should provide
      information about the benefits of pacifiers. Establishing for parents any
      plausible link between the protective mechanism of pacifiers and SIDS
      pathophysiology may be important in promoting pacifier use. 

PMID- 25864092
TI  - Movement disorders and brain iron overload in a new subtype of
      aceruloplasminemia.

PMID- 25864093
TI  - Pareidolia in Parkinson's disease without dementia: A positron emission
      tomography study.
AB  - BACKGROUND: Pareidolia, which is a particular type of complex visual illusion,
      has been reported to be a phenomenon analogous to visual hallucinations in
      patients with dementia with Lewy bodies. However, whether pareidolia is observed
      in Parkinson's disease (PD) or whether there are common underlying mechanisms of
      these two types of visual misperceptions remains to be elucidated. METHODS: A
      test to evoke pareidolia, the Pareidolia test, was administered to 53 patients
      with PD without dementia and 24 healthy controls. The regional cerebral metabolic
      rate of glucose was measured using 18F-fluorodeoxyglucose positron emission
      tomography in the PD patients. RESULTS: PD patients without dementia produced a
      greater number of pareidolic illusions compared with the controls. Pareidolia was
      observed in all of the patients having visual hallucinations as well as a subset
      of those without visual hallucinations. The number of pareidolic illusions was
      correlated with hypometabolism in the bilateral temporal, parietal and occipital
      cortices. The index of visual hallucinations was correlated with hypometabolism
      in the left parietal cortex. A region associated with both pareidolia and visual
      hallucinations was found in the left parietal lobe. CONCLUSIONS: Our study
      suggests that PD patients without dementia experience pareidolia more frequently
      than healthy controls and that posterior cortical dysfunction could be a common
      neural mechanism of pareidolia and visual hallucinations. Pareidolia could
      represent subclinical hallucinations or a predisposition to visual hallucinations
      in Lewy body disease.

PMID- 25864094
TI  - Incidence of maternal and neonatal outcomes in pregnancies complicated by ovarian
      masses.
AB  - PURPOSE: The purpose of our study is to estimate the incidence of adnexal mass
      and ovarian cancers during pregnancy and to evaluate their effects on obstetrical
      and fetal outcomes. METHODS: We conducted a population-based cohort study using
      data from The Healthcare Cost and Utilization Project-Nationwide Inpatient
      Sample. Cases of ovarian mass during delivery were identified using International
      Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM).
      Women were categorized into subgroups of malignant and benign masses. Logistic
      regression analysis was used to evaluate maternal and fetal outcomes. RESULTS:
      There were 7,785,583 deliveries between 2003 and 2011, of which 19,591 were
      diagnosed with ovarian masses during delivery, representing 0.25 % of all
      deliveries. Among these, 1:200 were malignant. The overall malignancy rate was
      0.12/10,000 deliveries. Apart from the increased rate of cesarean section, OR
      5.92 (95 % CI 4.12-8.40), and the risk of thrombosis, OR 5.52 (95 % CI 1.96
      15.53), there was no significant increase in maternal morbidity or mortality.
      Prematurity, OR 2.24 (95 % CI 1.48-3.40), was the only significant newborn risk
      in women with malignant ovarian tumors. Newborns of women with an ovarian mass
      had comparable risks of intrauterine growth restriction, preterm rupture of
      membrane and intrauterine death. CONCLUSION: The diagnosis of ovarian mass is
      rare during pregnancy and it is associated with an extremely low malignancy rate.
      Pregnant woman with a confirmed malignant ovarian tumor should be counseled
      regarding risks of prematurity, thrombosis and hysterectomy.

PMID- 25864096
TI  - Multidisciplinary OBGYN morbidity and mortality conference.
AB  - BACKGROUND AND PURPOSE: Obstetrics and gynecology (OB-GYN) morbidity and
      mortality conferences allow for review of cases with poor or avoidable outcomes.
      Little data exist on standardized formats for presentation and evaluation. We
      designed a multidisciplinary morbidity and mortality conference. We formally
      evaluated resident performance using the milestones format, and evaluated
      resident understanding of case concepts with a pre- and post-conference survey.
      METHODOLOGY: Our monthly conference was redesigned to incorporate the entire,
      residency program, OBGYN department members, nurses, midlevel providers, risk
      management, quality nurse director, and any additional staff who were involved in
      the case. Residents functioned as reviewers and presenters, and were then
      evaluated with a standard milestones-based evaluation by faculty members.
      Residents were also evaluated with a 10-point Likert scale for understanding of
      key case concepts, pre- and post-conference. RESULTS: Using a standardized format
      for presentation and evaluation improved resident presentation skills and ability
      to organize a vast amount of information from a chart into a valuable learning
      experience. Over a 6-month period, six cases were presented, and six actions were
      initiated for quality improvement. Resident understanding of concepts
      statistically improved after conference. CONCLUSION: M&M plays a crucial role not
      only in patient care, but also in resident education.

PMID- 25864095
TI  - Growth factors, silver dressings and negative pressure wound therapy in the
      management of hard-to-heal postoperative wounds in obstetrics and gynecology: a
      review.
AB  - PURPOSE: The last two decades witnessed the development of numerous innovative
      regimens for the management of patients with abnormally healing and infected
      wounds. Growth factors, negative pressure wound therapy (NPWT) and antiseptic
      dressings containing silver are examples of methods with best documented
      efficacy, being widely used in the treatment of acute and chronic post-traumatic
      wounds, burns and ulcers of various etiology. As far as obstetrics and gynecology
      are concerned, prevention and treatment of infected, hard-to-heal postoperative
      wounds is of crucial importance. This article reviews the available literature to
      discuss the possibilities for use, efficacy and cost-effectiveness of growth
      factors, NPWT and silver dressings in the treatment of difficult-to-heal
      postsurgical wounds in obstetrics and gynecology. MATERIALS AND METHODS: An
      extensive search of the English and Polish literature via PubMed and EMBASE
      databases was undertaken for articles published between January 1960 and April
      30, 2014 to identify articles that described and assessed use, efficacy and cost
      effectiveness of growth factors, silver dressings and NPWT in patients with hard
      to-heal postoperative wounds following obstetric or gynecological surgery.
      CONCLUSIONS: Literature review regarding the use of growth factors, NPWT and
      silver dressings suggests that these methods may play an important role in the
      management of wounds after invasive obstetric and gynecological procedures. Obese
      patients, patients after vulvectomy or prior radiation therapy may benefit most,
      however, due to non-numerous randomized reports, prospective studies on the use
      of above-mentioned methods in the treatment of postsurgical wounds following
      obstetric and gynecological interventions are required.

PMID- 25864097
TI  - The significance of a uterine rupture in subsequent births.
AB  - OBJECTIVE: To determine whether women with a previous uterine rupture have a
      higher risk of adverse perinatal outcome in subsequent births. METHODS: A
      retrospective study comparing all subsequent singleton cesarean deliveries (CD)
      of women with a previous uterine rupture, with CD of women with no such history,
      during the years 1988-2011 was conducted. RESULTS: Out of 34,601 singleton CD
      that occurred during the study period, 0.1 % (n = 46) were of women with a
      previous uterine rupture. Previous uterine rupture was significantly associated
      with preterm delivery (<37 weeks), low birth weight (<2500 g), cervical tears,
      and dehiscence of the uterine scar. Pregnancies following a previous uterine
      rupture were associated with lower Apgar scores at 5 min. However, the perinatal
      mortality rate did not differ between the two groups. A recurrent uterine rupture
      occurred in 15.2 % of patients with a previous uterine rupture. CONCLUSION:
      Previous uterine rupture is a risk factor for adverse maternal and perinatal
      outcome and specifically recurrent uterine rupture. Appropriate consultation
      regarding these risks is needed for patients with a previous uterine rupture.

PMID- 25864098
TI  - Survival patterns following brain metastases for patients with melanoma in the
      MAP-kinase inhibitor era.
AB  - Survival with BRAF-mutant metastatic melanoma is prolonged with MAP-kinase
      pathway inhibitors (MAPKi). Among patients with brain metastases (BM), however,
      the clinical course of MAPKi-treated patients is not well described. We therefore
      explored these patients' survival patterns compared to contemporary patients not
      treated with MAPKi. We analyzed 106 patients who developed melanoma BM between
      2007 and 2013. Of these, 37 (35%) received de novo MAPKi for BRAF-mutant disease,
      which preceded BM in 49%. Immunotherapy was given to 54% of MAPKi-treated
      patients and 94% of those who did not receive MAPKi. We evaluated the potential
      influence of patient characteristics, systemic therapies, and BM-directed
      treatments on time to appearance of new BM and overall survival. With a median
      follow-up of 8.0 months after initial BM, MAPKi use was an independent predictor
      of prolonged survival after BM diagnosis (median 14.1 vs 7.0 months, P = 0.03,
      adjusted hazard ratio 0.39). This survival advantage was driven by the 16.6-month
      median survival of patients who initiated MAPKi after BM were diagnosed, versus
      5.6 months if initiated prior to BM development (P = 0.03). Median survival from
      the onset of any systemic metastases was 22 months regardless of the timing of
      MAPKi relative to BM appearance. Time to in-brain progression was longer among
      patients whose MAPKi course was started after BM diagnosis, but MAPKi initiation
      prior to BM diagnosis was associated with longer time to intracranial
      involvement. These findings are consistent with potential MAPKi activity in
      intracranial melanoma.

PMID- 25864099
TI  - Completeness and concordancy of WHO grade assignment for brain and central
      nervous system tumors in the United States, 2004-2011.
AB  - Central nervous system (CNS) tumors are categorized and graded for clinical and
      research purposes according to the World Health Organization (WHO) scheme which
      segregates tumors by histological type and predicted biological behavior.
      However, reporting of WHO grade in pathological reports is inconsistent despite
      its collection in cancer registration. We studied the completeness, concordancy,
      and yearly trends in the collection of WHO grade for primary CNS tumors between
      2004 and 2011. Data from the Surveillance, Epidemiology and End Results program
      were analyzed for the percentage of histologically diagnosed primary CNS tumor
      cases with concordantly documented WHO grades between 2004 and 2011. Yearly
      trends were calculated with annual percentage changes (APC) and 95% confidence
      intervals (95% CI). Completeness and concordancy of the collection of WHO grade
      varied significantly by histological type and year. The percentage of cases with
      documented WHO grade increased significantly from 2004 to 2011: 39.0% of cases in
      2004 had documented WHO grade, while 77.5% of cases had documented grade in 2011
      (APC, 10.3; 95% CI: 9.0, 11.5). Among cases with documented WHO grade, the
      percentage graded concordantly increased significantly from 89.1% in 2004 to
      93.7% in 2007 (APC, 1.8; 95% CI: 1.0, 2.6) and these values varied over time by
      histological type. One common trend among all histologies was a significant
      increase in the percentage of cases with documented WHO grade. A sizeable
      proportion of reported CNS tumors collected by cancer registrars have
      undocumented WHO grade, while a much smaller proportion are graded discordantly.
      Data collection on grade has improved in completeness and concordancy over time.
      Efforts to further improve collection of this variable are essential for clinical
      care and the epidemiological surveillance of CNS tumors.

PMID- 25864100
TI  - Opsoclonus-myoclonus syndrome in a patient with an anaplastic oligoastrocytoma.

PMID- 25864101
TI  - Partial nephrectomy for T2 renal masses: contemporary trends and oncologic
      efficacy.
AB  - PURPOSE: Increasing popularity and improved technical feasibility of partial
      nephrectomy (PN) has encouraged urologists to treat larger renal masses with
      nephron-sparing surgery. We used a national database to characterize practice
      patterns for the surgical management of patients with T2 renal tumors and
      examined the effect of PN on cancer-specific survival in such patients. METHODS:
      Between 2001 and 2011, 10,259 patients with primary tumor size >7 cm confined to
      the kidney (T2) were treated surgically for kidney cancer. PN trends were
      examined using annual percentage change (APC). Multivariate survival models were
      developed to identify independent determinants of PN use and cancer-specific
      survival (CSS) following surgical treatment of kidney cancer. RESULTS: Overall,
      543 patients (5.29 %) were treated with PN versus 9716 (94.71 %) who underwent
      radical nephrectomy (RN). The use of PN increased progressively between 2001 and
      2011 (APC +11.1 %, p < 0.05). Male gender, geographic location, year of
      diagnosis, and disease stage were independent determinants of increased PN use
      (all p values <0.05). Cancer-specific mortality was not inferior for patients
      treated with PN versus RN (HR 0.68, 95 % CI 0.50-0.94). Male gender, younger age,
      white race, tumor size >10 cm, localized disease, and papillary histology were
      all associated with improved CSS with PN (all p values <0.05). CONCLUSIONS: PN is
      increasingly utilized to treat T2 renal masses. Our analysis demonstrates that PN
      for T2 renal masses has no contraindicated effect on CSS.

PMID- 25864102
TI  - Ethical issues in physical therapy.
AB  - Healthcare professionals can be confronted with a wide range of ethical and
      regulatory issues in today's ever-changing practice environments. While achieving
      best practice standards, physical therapists may need to compromise what is best
      for patients due to fiscally driven rules, regulations, and limited benefits.
      Scenarios may surface where ethical issues and associated dilemmas become
      paramount between what is versus what should be. A challenge that should be in
      the forefront of professional endeavors is staying current with published rules,
      regulations, and conditions of participation, as applied to various practice
      models and environments while still adhering to ethical codes. Knowing and
      utilizing available resources especially American Physical Therapy Association
      (APTA), websites, documents, and references can strengthen practice patterns and
      treatment options. 

PMID- 25864103
TI  - Ethical considerations in chronic musculoskeletal disease.
AB  - Chronic diseases compromise the life of the sufferer, encumber their families,
      and exert intractable burdens on the health-care system. With the aging of the
      population, such conditions have become the primary determinants of morbidity and
      mortality and the leading cause of disability in our society. Despite the serious
      challenges they impose, the ethical discourse engendered by them has lagged
      behind that of acute care medicine. Of particular relevance are the challenges to
      individual autonomy, as the dilemmas arising in the chronic care setting have not
      only medical but personal and societal dimensions, may require the input of
      multiple participants, and resolve over longer periods of time. As such, the
      conventional model of autonomy is often inadequate to address problems in the
      chronic care setting. This paper deals with this dilemma through an examination
      of a clinical scenario. A framework for the exploration of ethical problems in
      the chronic care setting is thus presented. 

PMID- 25864104
TI  - Ombrabulin plus cisplatin versus placebo plus cisplatin in patients with advanced
      soft-tissue sarcomas after failure of anthracycline and ifosfamide chemotherapy:
      a randomised, double-blind, placebo-controlled, phase 3 trial.
AB  - BACKGROUND: Ombrabulin (AVE8062) disrupts the vasculature of established tumours
      and has shown preclinical synergistic anti-tumour activity when combined with
      cisplatin. In this phase 3 trial, we aimed to assess the efficacy and safety of
      ombrabulin plus cisplatin compared with placebo plus cisplatin in patients with
      advanced soft-tissue sarcomas. METHODS: We did this multinational, randomised,
      double-blind, placebo-controlled phase 3 study at 44 centres in ten countries.
      Patients aged 18 years and older with metastatic soft-tissue sarcomas, an Eastern
      Cooperative Oncology Group performance status of 0-2, and who had previously
      received treatment with anthracycline and ifosfamide were randomly assigned (1:1)
      to intravenous infusion of ombrabulin 25 mg/m(2) plus cisplatin 75 mg/m(2) or
      intravenous infusion of placebo plus cisplatin 75 mg/m(2) every 3 weeks. Patients
      were allocated to treatment using a permuted blocks randomisation scheme (block
      size of four) via an interactive voice-response system, and stratified by
      histological subtype. Patients, medical staff, study investigators, and
      individuals who handled and analysed the data were masked to treatment
      assignment. Our primary endpoint was median progression-free survival in the
      intention-to-treat population. Safety analyses were done on all randomised
      patients who received at least one dose of study drug. This trial is now closed,
      and is registered with ClinicalTrials.gov, number NCT00699517. FINDINGS: Between
      June 13, 2008, and April 26, 2012, we randomly assigned 355 patients to
      ombrabulin plus cisplatin (n=176) or placebo plus cisplatin (n=179). Median
      duration of follow-up was 27.9 (IQR 20.9-33.2) in the placebo group and 30.5
      months (20.7-37.6) in the ombrabulin group. Progression-free survival was
      slightly, but significantly, improved in the ombrabulin group compared with the
      placebo group (median 1.54 months [95% CI 1.45-2.69] vs 1.41 [1.38-1.58] months;
      hazard ratio 0.76 [95% CI 0.59-0.98]; p=0.0302). Grade 3 or 4 adverse events
      occurred more frequently in individuals in the ombrabulin group than in those in
      the placebo group and included neutropenia (34 [19%] in the ombrabulin group vs
      14 [8%] in the placebo group) and thrombocytopenia (15 [8%] vs six [3%] for
      placebo). Adverse events leading to death occurred in 18 patients in the
      ombrabulin group and 10 patients in the placebo group. INTERPRETATION: The
      combination of ombrabulin and cisplatin significantly improved progression-free
      survival; however, it did not show a sufficient clinical benefit in patients with
      advanced soft-tissue sarcomas to support its use as a therapeutic option.
      Predictive biomarkers are needed for the rational clinical development of tumour
      vascular-disrupting drugs for soft-tissue sarcomas. FUNDING: Sanofi.

PMID- 25864105
TI  - Tumour vascular-disrupting agents in soft-tissue sarcoma.

PMID- 25864107
TI  - Live attenuated vaccines: Historical successes and current challenges.
AB  - Live attenuated vaccines against human viral diseases have been amongst the most
      successful cost effective interventions in medical history. Smallpox was declared
      eradicated in 1980; poliomyelitis is nearing global eradication and measles has
      been controlled in most parts of the world. Vaccines function well for acute
      diseases such as these but chronic infections such as HIV are more challenging
      for reasons of both likely safety and probable efficacy. The derivation of the
      vaccines used has in general not been purely rational except in the sense that it
      has involved careful clinical trials of candidates and subsequent careful follow
      up in clinical use; the identification of the candidates is reviewed. 

PMID- 25864106
TI  - Nature's favorite building block: Deciphering folding and capsid assembly of
      proteins with the HK97-fold.
AB  - For many (if not all) bacterial and archaeal tailed viruses and eukaryotic
      Herpesvirdae the HK97-fold serves as the major architectural element in
      icosahedral capsid formation while still enabling the conformational flexibility
      required during assembly and maturation. Auxiliary proteins or Delta-domains
      strictly control assembly of multiple, identical, HK97-like subunits into
      procapsids with specific icosahedral symmetries, rather than aberrant non
      icosahedral structures. Procapsids are precursor structures that mature into
      capsids in a process involving release of auxiliary proteins (or cleavage of
      Delta-domains), dsDNA packaging, and conformational rearrangement of the HK97
      like subunits. Some coat proteins built on the ubiquitous HK97-fold also have
      accessory domains or loops that impart specific functions, such as increased
      monomer, procapsid, or capsid stability. In this review, we analyze the numerous
      HK97-like coat protein structures that are emerging in the literature (over 40 at
      time of writing) by comparing their topology, additional domains, and their
      assembly and misassembly reactions. 

PMID- 25864108
TI  - A novel component from citrus, ginger, and mushroom family exhibits antitumor
      activity on human meningioma cells through suppressing the Wnt/beta-catenin
      signaling pathway.
AB  - Recurrent meningiomas constitute an uncommon but significant problem after
      standard (surgery and radiation) therapy failure. Current chemotherapies
      (hydroxyurea, RU-486, and interferon-alpha) are only of marginal benefit. There
      is an urgent need for more effective treatments for meningioma patients who have
      failed surgery and radiation therapy. Limonin, Tangeritin, Zerumbone, 6-Gingerol,
      Ganoderic Acid A, and Ganoderic Acid DM are some of the plant derivatives that
      have anti-tumorgenic properties and cause cell death in meningioma cells in
      vitro. Due to its ease of administration, long-term tolerability, and low
      incidence of long-term side effects, we explored its potential as a therapeutic
      agent against meningiomas by examining their efficacy in vitro against meningioma
      cells. Treatment effects were assessed using MTT assay, Western blot analysis,
      caspases assay, and DNA fragmentation assay. Results indicated that treatments of
      IOMM-Lee and CH157MN meningioma cells with Limonin, Tangeritin, Zerumbone, 6
      Gingerol, Ganoderic Acid A, and Ganoderic Acid DM induced apoptosis with enhanced
      phosphorylation of glycogen synthase kinase 3 beta (GSK3beta) via inhibition of
      the Wnt5/beta-catenin pathway. These drugs did not induce apoptosis in normal
      human neurons. Other events in apoptosis included downregulation of tetraspanin
      protein (TSPAN12), survival proteins (Bcl-XL and Mcl-1), and overexpression
      apoptotic factors (Bax and caspase-3). These results provide preliminary strong
      evidence that medicinal plants containing Limonin, Tangeritin, 6-Gingerol,
      Zerumbone, Ganoderic Acid A, and Ganoderic Acid DM can be applied to high-grade
      meningiomas as a therapeutic agent, and suggests that further in vivo studies are
      necessary to explore its potential as a therapeutic agent against malignant
      meningiomas.

PMID- 25864109
TI  - ALDH1 might influence the metastatic capability of HeLa cells.
AB  - Recent data suggest that tumor persistence and recurrence could be caused by the
      presence of cancer stem cells (CSCs). Aldehyde dehydrogenase 1 (ALDH1) has been
      implicated in cancer pathogenesis and used as a CSC marker. We previously
      reported that cervical carcinoma contains a small subpopulation of cells
      expressing ALDH1 [1]. In this study, we used small interfering RNA to suppress
      ALDH1 expression and introduced an ALDH1 reporting vector into HeLa cells
      followed by various in vitro assays. We showed that knockdown of ALDH1 expression
      reduced the cell migration ability of HeLa cells, whereas augmented expression of
      ALDH1 increased cell migration. However, there was no difference in the cellular
      proliferation, apoptosis, cell cycle, and invasion. These results indicate that
      ALDH1 is directly involved in HeLa migration.

PMID- 25864111
TI  - 1,5-Anhydroglucitol: a new predictor of neonatal birth weight in diabetic
      pregnancies.
AB  - OBJECTIVE: To determine whether 1,5-anhydroglucitol is predictive of neonatal
      birth weight. STUDY DESIGN: A retrospective cohort study including 85 pregnancies
      complicated by diabetes (Type 1=37, Type 2=24, gestational=24). Women had
      simultaneous hemoglobin A1c and 1,5-anhydroglucitol measurements every 4-8 weeks
      throughout pregnancy until delivery. Neonatal birth weight was evaluated by
      standardized z-scores. Linear regression analysis was performed to determine an
      association of 1,5-anhydroglucitol with neonatal birth weight z-score. RESULTS:
      Type 1 diabetic patients had the lowest mean 1,5-anhydroglucitol of 3.5mcg/mL
      (SD=1.6mcg/mL) and highest mean hemoglobin A1c of 6.5% (SD=0.74%) compared to
      gestational diabetic patients who had the highest mean 1,5-anhydroglucitol of
      6.7mcg/mL (SD=3.8mcg/mL) and lowest mean hemoglobin A1c of 6.0% (SD=0.94%). Mean
      1,5-anhydroglucitol values were significantly different between diabetes types
      (p<0.01). Mean neonatal birth weight was above population averages for all
      diabetes classifications, although mean birth weight z-scores did not differ
      significantly between diabetic types (p=0.38). Multivariate linear regression
      showed a negative association between log-transformed 1,5-anhydroglucitol and
      birth weight (coefficient -0.82, 95% CI -1.19, -0.46). CONCLUSION: In pregnancies
      complicated by diabetes, low 1,5-anhydroglucitol was associated with increased
      neonatal birth weight. 1,5-Anhydroglucitol may be useful in the assessment of
      glycemic control in pregnancy in addition to A1c.

PMID- 25864110
TI  - C-reactive protein inhibits expression of N-cadherin and ZEB-1 in murine colon
      adenocarcinoma.
AB  - Epithelial-to-mesenchymal transition (EMT) is thought to play a key role in
      cancer cell invasion and metastasis. We previously demonstrated that cancer cell
      migration is inhibited by C-reactive protein (CRP), which is widely used as a
      biomarker of inflammation, though its functions are not fully understood. In the
      present study, we evaluated the effect of CRP on cancer cell migration and
      expression of mesenchymal and epithelial markers of EMT and of related
      transcription factors. MCA-38 murine colon adenocarcinoma cells were
      subcutaneously inoculated into the backs of C57BL/6 mice, which also received 1
      MUg of recombinant mouse CRP or vehicle (phosphate-buffered saline)
      subcutaneously every 3 days for 4 weeks. Thereafter, the mice were sacrificed for
      evaluation using quantitative real-time polymerase chain reaction (PCR) and
      immunohistochemistry. There was no statistical difference in tumor size between
      the control and CRP groups, but CRP dose-dependently inhibited MCA-38 cell
      migration. PCR analysis confirmed that CRP suppresses expression of N-cadherin (p
      < 0.01), a mesenchymal marker of EMT, and ZEB-1, an EMT-related transcription
      factor (p < 0.01). These findings suggest that CRP inhibits EMT in a MCA-38 tumor
      bearing mouse model. CRP may thus be a potentially useful tool for preventing
      cancer progression through suppression of EMT.

PMID- 25864112
TI  - Rifampicin in the treatment of severe intrahepatic cholestasis of pregnancy.
AB  - OBJECTIVE: To describe the use of combined ursodeoxycholic acid (UDCA) and
      rifampicin treatment in intrahepatic cholestasis of pregnancy (ICP). STUDY
      DESIGN: A questionnaire survey of 27 women with 28 affected pregnancies
      identified via the UK and International Obstetric Medicine forum. The clinical
      case notes of women with ICP treated with combined UDCA and rifampicin therapy
      were reviewed, and data regarding maternal and perinatal outcomes extracted.
      RESULTS: Serum bile acids remained high whilst taking UDCA as monotherapy. In 14
      pregnancies (54%) serum bile acids decreased following the introduction of
      rifampicin. In 10 pregnancies (38%), there was a 50% reduction in serum bile
      acids. There were no adverse effects reported with either drug. CONCLUSIONS: This
      is the first report of the use of rifampicin in ICP. The data suggest that
      combined treatment with UDCA and rifampicin is an effective way of treating women
      with severe ICP who do not respond to treatment with UDCA alone.

PMID- 25864113
TI  - Upregulation of long noncoding RNA PEG10 associates with poor prognosis in
      diffuse large B cell lymphoma with facilitating tumorigenicity.
AB  - Diffuse large B cell lymphoma (DLBCL) is one of the most common malignancies
      worldwide. To date, there has been little progress in improving the overall
      survival of DLBCL patients. Emerging evidences have implicated that long
      noncoding RNAs (lncRNAs) have important regulatory roles in fundamental
      biological processes, and some of them are involved in cancer initiation,
      development and progression. This study was to investigate the expression of
      lncRNA PEG10 in a cohort of DLBCL patients to assess its clinical value and
      biological function in DLBCL. We first found that the expression of PEG10 was
      upregulated in DLBCL tumorous tissues and that cell lines compared with the
      normal. Moreover, we illustrated that PEG10 was significantly correlated with B
      symptoms, IPI score, CHOP-like treatment and rituximab. In addition, ROC(AUC) of
      PEG10 was up to 0.8228, implicating that PEG10 could be a diagnostic marker for
      distinguishing DLBCL from normal. Importantly, we verified that PEG10 was a key
      independent predictive factor for DLBCL prognosis from sizable samples through
      the longtime follow-ups. Furthermore, we revealed that knockdown of PEG10
      expression by siRNA could lead to growth arrest and cell apoptosis in vitro. Our
      results suggested that PEG10 could represent a novel indicator of poor prognosis
      and might be served as a potential target for the diagnosis and gene therapy of
      DLBCL. 

PMID- 25864115
TI  - Dietary oregano essential oil alleviates experimentally induced coccidiosis in
      broilers.
AB  - An experiment was conducted to determine the effects of oregano essential oil on
      growth performance and coccidiosis prevention in mild challenged broilers. A
      total of 250 1-d-old chicks were used in a completely randomized design with 5
      treatments and 5 replicates with 10 birds in each replication. Experimental
      treatments included: (1) negative control (NC; unchallenged), (2) positive
      control (PC; challenged with sporulated oocysts of Eimeria), (3) PC fed 200 ppm
      Diclazuril in diet, (4) PC fed 300 ppm oregano oil in diet, and (5) PC fed 500
      ppm oregano oil in diet. At 22 d of age, all the experimental groups except for
      NC were challenged with 50-fold dose of Livacox T as a trivalent live attenuated
      coccidiosis vaccine. On d 28, two birds were slaughtered and intestinal
      coccidiosis lesions were scored 0-4. Moreover, dropping was scored in the scale
      of 0-3, and oocysts per gram feces (OPG) were measured. Oregano oil at either
      supplementation rate increased body weight gain (P=0.039) and improved feed
      conversion ratio (P=0.010) from d 22 to 28, when compared with PC group. Using
      500 ppm oregano oil in challenged broilers diet increased European efficiency
      factor than PC group (P=0.020). Moreover, challenged broilers fed 500 ppm oregano
      oil or Diclazuril in diets displayed lower coccidiosis lesions scores in upper
      (P=0.003) and middle (P=0.018) regions of intestine than PC group, with the
      effect being similar to unchallenged birds. In general, challenged birds fed 500
      ppm oregano oil or Diclazuril in diets had lower OPG (P=0.001), dropping scores
      (P=0.001), litter scores (P=0.001), and pH of litter (P=0.001) than PC group. It
      could be concluded that supplementation of oregano oil at the dose of 500 ppm in
      diet may have beneficial effect on prevention of coccidiosis in broilers.

PMID- 25864116
TI  - Erratum to: Radiosurgery reirradiation for high-grade glioma recurrence: a
      retrospective analysis.

PMID- 25864117
TI  - Compound Tufuling Granules ([characters: see text]) regulate glucose transporter
      9 expression in kidney to influence serum uric acid level in hyperuricemia mice.
AB  - OBJECTIVE: To explore the effect of Compound Tufuling Granules ([characters: see
      text], CTG) on regulating glucose transporter 9 (GLUT9) expression in the kidney
      to influence the uric acid excretion by the kidney and serum uric acid (SUA)
      level in hyperuricemia mice. METHODS: Sixty Kunming male mice were randomly
      divided into the control group, model group, benzbromarone group, and CTG high-,
      middle- and low-dose groups. The yeast extract and uricase inhibition method were
      used to build hyperuricemia model, and the corresponding drugs were administrated
      on the 7th day. On the 21st day the 24-h urine was collected, on the 22nd day the
      blood was collected, the SUA level was detected by uricase colorimetry, and the
      mRNA and protein expressions of GLUT9 were detected by quantitative real-time
      polymerase chain reaction and Western blot, respectively. RESULTS: Compared with
      the model group, the levels of SUA and the mRNA and protein expressions of GLUT9
      were significantly decreased, and the fraction excretion of uric acid (FEUA) was
      significantly increased in the CTG groups and benzbromarone group (all P<0.05).
      There was no significant difference in the above indicators between the CTG high
      dose group and benzbromarone group (P>0.05). SUA is positively related to the
      GLUT9 mRNA and protein expressions in the kidney (P<0.05 or P<0.01). CONCLUSIONS:
      CTG can significantly reduce the SUA and increase the FEUA. In addition, CTG can
      effectively inhibit the mRNA and protein expressions of GLUT9 in the kidney of
      hyperuricemia mice to inhibit the uric acid re-absorption, promote uric acid
      excretion and reduce SUA.

PMID- 25864119
TI  - The Third Symposium on Innovative Polymers for Controlled Delivery, September 16
      19, 2014, Suzhou, China. Preface.

PMID- 25864118
TI  - Differential expression of microRNA in endothelial cells incubated with serum of
      hypertension patients with blood-stasis syndrome.
AB  - OBJECTIVE: To screen out blood-stasis syndrome (BSS)-associated microRNA and
      therefore determine the possible target for treating hypertension. METHODS: A
      high-energy sequencing method and digital gene expression sequencing theory were
      adopted to sequence microRNA (miRNA) and messenger RNA (mRNA), and to determine
      differential expression in human umbilical vein endothelial cells incubated with
      serum samples from hypertension patients with or without BSS, and healthy
      controls. The results were confirmed using gene prediction software. RESULTS: A
      total of 13 miRNAs and 11 mRNAs showed statistical difference both in the
      BSS/normal groups and BSS/non-BSS groups, respectively. Four pairs of target
      mRNA/miRNA were identified: FRMD4A/hsa-miR-34a, MAP3K14/hsa-miR-34a, PER1/hsa-miR
      34a, and FGF2/hsa-miR-132. CONCLUSION: Four mRNA/miRNA pairs mentioned above seem
      to be involved in pathogenesis and maintenance of hypertension with BSS.

PMID- 25864120
TI  - [Upper eyelid congenital coloboma, aethiology pathogenesis and management].
AB  - Coloboma of the upper eyelid is a rare congenital disease. It is defined as an
      agenesis of the eyelid free edge. Multiple patho-physiological theories exist
      about its etiology. The surgical therapeutic management of this malformation is
      clearly codified. We illustrate the presentation by two cases treated in the
      Groupement Hospitalier Nord of Lyon University Hospital. 

PMID- 25864121
TI  - Neural network operators: Constructive interpolation of multivariate functions.
AB  - In this paper, the interpolation of multivariate data by operators of the neural
      network type is proved. These operators can also be used to approximate
      continuous functions defined on a box-domain of R(d). In order to show this fact,
      a uniform approximation theorem with order is proved. The rate of approximation
      is expressed in terms of the modulus of continuity of the functions being
      approximated. The above interpolation neural network operators are activated by
      suitable linear combinations of sigmoidal functions constructed by a procedure
      involving the well-known central B-spline. The implications of the present theory
      with the classical theories of neural networks and sampling operators are
      analyzed. Finally, several examples with graphical representations are provided. 

PMID- 25864122
TI  - Modelling the insect Mushroom Bodies: Application to sequence learning.
AB  - Learning and reproducing temporal sequences is a fundamental ability used by
      living beings to adapt behaviour repertoire to environmental constraints. This
      paper is focused on the description of a model based on spiking neurons, able to
      learn and autonomously generate a sequence of events. The neural architecture is
      inspired by the insect Mushroom Bodies (MBs) that are a crucial centre for
      multimodal sensory integration and behaviour modulation. The sequence learning
      capability coexists, within the insect brain computational model, with all the
      other features already addressed like attention, expectation, learning
      classification and others. This is a clear example that a unique neural structure
      is able to cope concurrently with a plethora of behaviours. Simulation results
      and robotic experiments are reported and discussed. 

PMID- 25864123
TI  - Divergent androgen regulation of unfolded protein response pathways drives
      prostate cancer.
AB  - The unfolded protein response (UPR) is a homeostatic mechanism to maintain
      endoplasmic reticulum (ER) function. The UPR is activated by various
      physiological conditions as well as in disease states, such as cancer. As
      androgens regulate secretion and development of the normal prostate and drive
      prostate cancer (PCa) growth, they may affect UPR pathways. Here, we show that
      the canonical UPR pathways are directly and divergently regulated by androgens in
      PCa cells, through the androgen receptor (AR), which is critical for PCa
      survival. AR bound to gene regulatory sites and activated the IRE1alpha branch,
      but simultaneously inhibited PERK signaling. Inhibition of the IRE1alpha arm
      profoundly reduced PCa cell growth in vitro as well as tumor formation in
      preclinical models of PCa in vivo. Consistently, AR and UPR gene expression were
      correlated in human PCa, and spliced XBP-1 expression was significantly
      upregulated in cancer compared with normal prostate. These data establish a
      genetic switch orchestrated by AR that divergently regulates the UPR pathways and
      suggest that targeting IRE1alpha signaling may have therapeutic utility in PCa. 

PMID- 25864125
TI  - Biodegradable and Titanium Osteosynthesis Provide Similar Stability for
      Orthognathic Surgery.
AB  - PURPOSE: The purpose of this study was to test the hypothesis that there is no
      difference in skeletal stability and material-related complications for titanium
      or biodegradable fixation when used for various orthognathic surgeries. MATERIALS
      AND METHODS: A systematic and electronic search of several databases with
      specific keywords, a reference search, and a manual search through September 2014
      was performed. The inclusion criteria were clinical human studies, including
      randomized controlled trials, controlled clinical trials, and retrospective
      studies, with the aim of comparing titanium and biodegradable osteosynthesis
      after various orthognathic surgeries. The outcome variables of horizontal and
      vertical relapse using cephalometrics and material usability were statistically
      analyzed. RESULTS: The initial PubMed search identified 557 studies, 22 of which
      met the inclusion criteria (8 randomized controlled trials, 10 controlled
      clinical trials, and 4 retrospective studies). No statistical difference was
      found between the 2 groups regarding skeletal stability after various
      orthognathic surgeries. There was no statistical difference with regard to wound
      problems, plate and screw removal, and palpability between biodegradable and
      titanium osteosynthesis, but there was a statistical difference with regard to
      intraoperative fracture of plates and screws in the biodegradable group.
      CONCLUSION: The results of this meta-analysis support the hypothesis that
      biodegradable fixation devices offer similar skeletal stability as titanium
      fixation for orthognathic surgery. The results of this study also show that
      titanium fixation produced fewer broken screws during surgery compared with
      biodegradable screws.

PMID- 25864124
TI  - Fusion protein of retinol-binding protein and albumin domain III reduces liver
      fibrosis.
AB  - Activated hepatic stellate cells (HSCs) play a key role in liver fibrosis, and
      inactivating HSCs has been considered a promising therapeutic approach. We
      previously showed that albumin and its derivative designed for stellate cell
      targeting, retinol-binding protein-albumin domain III fusion protein (referred to
      as R-III), inactivate cultured HSCs. Here, we investigated the mechanism of
      action of albumin/R-III in HSCs and examined the anti-fibrotic potential of R-III
      in vivo. R-III treatment and albumin expression downregulated retinoic acid (RA)
      signaling which was involved in HSC activation. RA receptor agonist and
      retinaldehyde dehydrogenase overexpression abolished the anti-fibrotic effect of
      R-III and albumin, respectively. R-III uptake into cultured HSCs was
      significantly decreased by siRNA-STRA6, and injected R-III was localized
      predominantly in HSCs in liver. Importantly, R-III administration reduced CCl4-
      and bile duct ligation-induced liver fibrosis. R-III also exhibited a preventive
      effect against CCl4-inducd liver fibrosis. These findings suggest that the anti
      fibrotic effect of albumin/R-III is, at least in part, mediated by downregulation
      of RA signaling and that R-III is a good candidate as a novel anti-fibrotic drug.

PMID- 25864126
TI  - Accuracy of diagnosing double corpora lutea and twin pregnancy by measuring serum
      progesterone and bovine pregnancy-associated glycoprotein 1 in the first
      trimester of gestation in dairy cows.
AB  - Progesterone (P4) and bovine pregnancy-associated glycoprotein 1 (bPAG-1)
      concentrations during gestation are dependent on the number of CL and fetuses,
      respectively. The objective of this present study was to measure and evaluate the
      usefulness of measuring the P4 and bPAG-1 concentrations in cases of single
      versus twin pregnancies and one versus two CL at the first 4 months of gestation.
      We hypothesized that both the number of the CL and the number of fetus might have
      an effect on P4 and pregnancy protein concentrations, and we can set up
      clinically useful threshold levels to predict twin gestations. Eighty-four
      Holstein-Friesian dairy cows were enrolled in this prospective observational
      clinical trial. Blood was collected at time point 1: between Days 29 and 42, time
      point 2: between Days 57 and 70, time point 3: between Days 85 and 98, and time
      point 4: between Days 113 and 126 of gestation, and bPAG-1 and P4 concentrations
      were measured. Binary logistic regression analyzing serum P4 concentrations
      differed at time point 2 compared with baseline level, but the area under the
      curve (AUC) had low sensitivity. The bPAG-1 concentrations were statistically
      different at each time point of gestation. The AUC cutoff values of serum bPAG-1
      concentrations were sufficiently sensitive to differentiate between twin
      gestations from singleton ones. At time points 3 (cutoff value of 3.4 ng/mL) and
      4 (cutoff value of 56.5 ng/mL), statistically significant differences with low
      sensitivity, high specificity, and a high AUC were found. On the basis of these
      results, the diagnosis of twin pregnancy using pregnancy protein measurements is
      clinically insufficient before Day 85 of gestation; however, the ability to
      confirm the early twin pregnancy diagnosis with bPAG-1 measurements appears to be
      promising. To achieve high sensitivity, further studies are required.

PMID- 25864127
TI  - The cure for the cynical physician: Gratitude and global health.

PMID- 25864128
TI  - Fathers' and co-mothers' voices about breastfeeding and equality - A Swedish
      perspective.
AB  - BACKGROUND: Breastfeeding has benefits for mother and child and the partner's
      support influences the decision as well as the duration of breastfeeding. The aim
      of this study was to describe partners' knowledge and feelings regarding
      breastfeeding and how they reason about equality and involvement during the
      lactation period. METHODS: A qualitative study using semi-structured interviews
      with 7 male and 2 female partners (labelled co-mothers) of breastfeeding mothers.
      The interviews were transcribed and analysed using a phenomenological approach.
      RESULTS: The main theme Wish for the child to be breastfed/get breast milk
      described the informants' desire that their child was breastfed and this desire
      was based on knowledge of benefits of breastfeeding but also on intuitive
      feelings of breastfeeding as something natural. The main theme Effect of
      breastfeeding on fathers/co-mothers described how breastfeeding affected the
      informants and their relationship to the child and the mother in different ways.
      The main theme Adaptation and acceptance described how informants accepted the
      impact that breastfeeding had and/or adapted to it and continued to wish for the
      child to receive breast milk. CONCLUSION: The informants desired that their
      children be breastfed/get breast milk. Breastfeeding affected the informants in
      different ways, which they handled by adapting to and accepting the situation,
      and they expressed a continued desire that their children be breastfed/get breast
      milk. Parental classes should include both parents to be and address how
      breastfeeding can be successfully performed and supported without threatening the
      equality between the parents.

PMID- 25864129
TI  - 'I really needed help': What mothers say about their post-birth care in
      Queensland, Australia.
AB  - BACKGROUND: Australian mothers consistently rate postnatal care as the poorest
      aspect of their maternity care, and researchers and policymakers have widely
      acknowledged the need for improvement in how postnatal care is provided. AIM: To
      identify and analyse mothers' comments about postnatal care in their free text
      responses to an open ended question in the Having a Baby in Queensland Survey,
      2010, and reflect on their implications for midwifery practice and maternity
      service policies. METHODS: The survey assessed mothers' experiences of maternity
      care four months after birth. We analysed free-text data from an open-ended
      question inviting respondents to write 'anything else you would like to tell us'.
      Of the final survey sample (N=7193), 60% (N=4310) provided comments, 26% (N=1100)
      of which pertained to postnatal care. Analysis included the coding and
      enumeration of issues to identify the most common problems commented on by
      mothers. Comments were categorised according to whether they related to in
      hospital or post-discharge care, and whether they were reported by women birthing
      in public or private birthing facilities. RESULTS: The analysis revealed
      important differences in maternal experiences according to birthing sector:
      mothers birthing in public facilities were more likely to raise concerns about
      the quality and/or duration of their in-hospital stay than those in private
      facilities. Conversely, mothers who gave birth in private facilities were more
      likely to raise concerns about inadequate post-discharge care. Regardless of
      birthing sector, however, a substantial proportion of all mothers spontaneously
      raised concerns about their experiences of inadequate and/or inconsistent
      breastfeeding support. CONCLUSION: Women who birth in private facilities were
      more likely to spontaneously report concerns about their level of post-discharge
      care than women from public facilities in Queensland, and publically provided
      community based care is not sufficient to meet women's needs. Inadequate or
      inconsistent professional breastfeeding support remains a major issue for early
      parenting women regardless of birthing sector.

PMID- 25864130
TI  - Normal breast tissue estrogen levels.

PMID- 25864131
TI  - Sponsoring public transport and health in older people.

PMID- 25864132
TI  - Multi-Input Single Output SSSC based damping controller design by a hybrid
      Improved Differential Evolution-Pattern Search approach.
AB  - In this paper, a hybrid Improved Differential Evolution and Pattern Search
      (hIDEPS) approach is proposed for the design of a PI-Type Multi-Input Single
      Output (MISO) Static Synchronous Series Compensator (SSSC) based damping
      controller. The improvement in Differential Evolution (DE) algorithm is
      introduced by a simple but effective scheme of changing two of its most important
      control parameters i.e. step size and crossover probability with an objective of
      achieving improved performance. Pattern Search (PS) is subsequently employed to
      fine tune the best solution provided by modified DE algorithm. The superiority of
      a proposed hIDEPS technique over DE and improved DE has also been demonstrated.
      At the outset, this concept is applied to a SSSC connected in a Single Machine
      Infinite Bus (SMIB) power system and then extended to a multi-machine power
      system. To show the effectiveness and robustness of the proposed design approach,
      simulation results are presented and compared with DE and Particle Swarm
      Optimization (PSO) optimized Single Input Single Output (SISO) SSSC based damping
      controllers. It is observed that the proposed approach yield superior damping
      performance compared to some approaches available in the literature. 

PMID- 25864133
TI  - Testing a model of caffeinated alcohol-specific expectancies.
AB  - INTRODUCTION: The present study sought to further understand the association
      between caffeinated alcoholic beverage (CAB) use and alcohol-related risks. In
      particular, we focused on the role of two identified expectancies specific to CAB
      use: intoxication enhancement and avoidance of negative consequences. Although
      outcome expectancies are consistent predictors of substance use, limited research
      has examined expectancies related to CAB use and their association with alcohol
      related behaviors, such as protecting themselves from alcohol-related harms.
      Consequently, the present study examined CAB-specific expectancies and protective
      behavioral strategies (PBS) as mediators of CAB use and negative consequences.
      METHODS: Participants were 322 (219 women) college drinkers who completed self
      report measures of typical CAB and alcohol use, CAB-specific expectancies, PBS
      use, and alcohol-related harms. RESULTS: Structural equation modeling revealed,
      after controlling for typical non-CAB heavy alcohol use, a significant indirect
      effect of CAB use to alcohol-related problems through avoidance of negative
      consequences CAB expectancies and PBS use. However, intoxication enhancement
      expectancies did not mediate this association. CONCLUSIONS: Our findings indicate
      that heavier CAB use was associated with stronger expectations that drinking CABs
      can help avoid negative consequences. These beliefs were related to using fewer
      PBS when drinking and a greater likelihood of experiencing problems. Given that
      these expectancies may be underlying mechanisms of CAB use, their inclusion in
      existing alcohol interventions may be beneficial.

PMID- 25864134
TI  - Marijuana use, craving, and academic motivation and performance among college
      students: An in-the-moment study.
AB  - INTRODUCTION: Marijuana is the most commonly used illicit substance in the U.S.,
      with high rates among young adults in the state of Colorado. Chronic, heavy
      marijuana use can impact cognitive functioning, which has the potential to
      influence academic performance of college students. It is possible that craving
      for marijuana may further contribute to diminished cognitive and affective
      functioning, thus leading to poor outcomes for students. METHODS: College student
      marijuana users (n=57) were recruited based on heavy use and completed ecological
      momentary assessment (EMA) via text-messaging. The association between marijuana
      use and craving in a college setting was explored, as well as how these variables
      might relate to academic motivation, effort and success. The participants were
      sent text messages for two weeks, three times per day at random times. RESULTS: A
      temporal association between craving and marijuana use was found, where momentary
      craving positively predicted greater marijuana use. Similarly, as craving levels
      increased, the number of minutes spent studying decreased at the next assessment
      point. A negative association between momentary craving for marijuana and
      academic motivation was found in the same moment. Greater academic self-efficacy
      positively predicted cumulative GPA, while average minutes spent smoking
      marijuana was negatively related. CONCLUSIONS: Using EMA, marijuana craving and
      use were significantly related. These findings provide further evidence that
      heavy marijuana use is negatively associated with academic outcomes.

PMID- 25864135
TI  - Personality traits of problem gamblers with and without alcohol dependence.
AB  - INTRODUCTION: A large proportion of individuals with gambling disorder also
      present with a history of alcohol dependence, but few studies have directly
      examined the relationship between these two conditions. This study's primary and
      secondary aims were to 1) examine the relationship of personality traits to co
      occurring lifetime (current/past) alcohol dependence status, while 2) accounting
      for differences in gambling characteristics and co-occurring psychiatric
      disorders among problem/pathological gamblers recruited from the community.
      METHODS: Problem/pathological gamblers (N=150) completed measures of personality
      traits and gambling characteristics (e.g., gambling severity, gambling
      involvement, delayed discounting of monetary rewards), and were clinically
      interviewed for co-occurring psychiatric disorders. RESULTS: A co-occurring
      lifetime diagnosis of alcohol dependence (n=61, 40.7%) was associated with lower
      personality scores for Control, Well-Being, Achievement, Traditionalism, and Harm
      Avoidance, as well as higher scores for Alienation (Tellegen & Waller, 1994) in
      bivariate analyses. Problem/pathological gamblers with lifetime alcohol
      dependence reported greater lifetime gambling severity, greater past-year
      gambling involvement, steeper delayed discounting, and a greater likelihood of
      current and lifetime substance dependence, lifetime antisocial personality
      disorder, and current unipolar mood disorders. Multivariate analyses indicated
      that lower Control, Traditionalism, and Well-Being and a co-occurring lifetime
      substance dependence diagnosis best accounted for a co-occurring lifetime alcohol
      dependence diagnosis in problem/pathological gamblers. CONCLUSIONS:
      Problem/pathological gamblers with co-occurring lifetime alcohol dependence
      demonstrate addictive behavior across multiple domains and report a personality
      style characterized by hopelessness, impaired control, and resistance to
      externally-motivated treatment approaches. Implications for the treatment of
      these complex cases are discussed.

PMID- 25864136
TI  - Emotion dysregulation facets as mediators of the relationship between PTSD and
      alcohol misuse.
AB  - INTRODUCTION: Posttraumatic stress disorder (PTSD) and alcohol misuse, which
      frequently co-occur among combat veterans, have been linked to emotion
      dysregulation. Emotion dysregulation may explain the link between PTSD and
      alcohol misuse, and this investigation tested emotion dysregulation as a mediator
      of that relationship. METHOD: Correlations between PTSD symptoms and cluster
      symptoms, emotion dysregulation full and subscales, and alcohol misuse were
      examined in a sample of 139 combat Operation Enduring Freedom/Operation Iraqi
      Freedom/Operation New Dawn veterans (45% African American; 89% men). Emotion
      dysregulation full scale and subscales were examined as mediators of the
      relationship between PTSD symptoms and alcohol misuse for the full sample and men
      only. RESULTS: PTSD symptoms and symptom clusters, emotion dysregulation, and
      alcohol misuse showed positive correlations for the full sample and men only.
      Neither the full scale of emotion dysregulation nor the facets of emotion
      dysregulation mediated the relationship between PTSD symptoms and alcohol misuse
      for the full sample; among men, the Impulse Control Difficulties when Upset and
      Lack of Emotional Clarity subscales were mediators of that relationship.
      CONCLUSIONS: Impulse control difficulties and lack of emotional clarity may play
      an important role in the link between PTSD and alcohol misuse for male veterans
      and should be an important target in treatment for individuals with both
      disorders. Addressing impulse control difficulties and lack of emotional clarity
      in those with PTSD and alcohol misuse may improve outcomes by helping individuals
      identify and describe upsetting emotions and develop healthy coping alternatives
      to alcohol misuse.

PMID- 25864137
TI  - [The role of beta-blockers in patients with metabolic syndrome and hypertension].
AB  - The choice of treatment of patients with hypertension should not be based solely
      on the blood pressure value, because the risk of cardiovascular diseases are
      influenced by the presence and magnitude of other risk factors, too. The presence
      of a metabolic disease (diabetes mellitus, metabolic syndrome) itself categorizes
      the patient as a high risk individual. In such cases the use of combined
      treatment is usually considered. For example, in case of hypertension aggravated
      by left ventricular dysfunction, ischaemic heart disease or cardiac
      insufficiency, beta-blocker treatment is usually included in the combination of
      the first setting.

PMID- 25864138
TI  - [Analysis of laboratory data of 155 patients with pheochromocytoma-paraganglioma
      syndrome diagnosed during the past 20 years].
AB  - INTRODUCTION: Laboratory diagnosis of pheochromocytoma-paraganglioma syndrome has
      been markedly improved during the past two decades. AIM: Retrospective assessment
      of diagnostic utility of urinary catecholamines and their metabolites as well as
      serum chromogranin A in 155 patients diagnosed at the 2nd Department of Medicine,
      Semmelweis University. METHOD: Urinary catecholamines and metabolites were
      measured using high-performance liquid chromatography with electrochemical
      detection in 155 patients with pheochromocytoma-paraganglioma (of whom 28.4% had
      hereditary background) and in 170 non-pheochromocytoma patients used as controls.
      Serum chromogranin A was measured by immunoradiometry. RESULTS: Sensitivity
      (93.2%) and specificity (87.0%) of urinary fractionated metanephrines were higher
      than those of urinary catecholamines (90.9% vs. 85.7%, respectively) and serum
      chromogranin A (88.7% and 77.5%, respectively). Urinary normetanephrine and serum
      chromogranin A correlated positively with tumor size (r = 0.552, p<0.0001 and r =
      0.618, p<0.0001, respectively). CONCLUSIONS: These data confirm the diagnostic
      utility of urinary catecholamines and their metabolites. Urinary normetanephrine
      and serum chromogranin A may help to estimate tumour mass and probably tumour
      progression.

PMID- 25864139
TI  - [Exploration of attitudes about healthy nutrition based on a questionnaire
      survey].
AB  - INTRODUCTION: Nowadays the number of people suffering from different non
      communicable diseases is continuously rising. However, the risk of the incidence
      of these diseases can be reduced with the help of conscious and healthy
      lifestyle. AIM: The main aim of the study was to explore Hungarian consumers'
      attitude related to healthy diet. METHOD: A questionnaire survey was conducted
      with 473 respondents. RESULTS: According to the participants it is difficult to
      make head or tail of information about healthy nutrition, and the "Internet" is
      the most frequently used source of information. With cluster analysis 3
      significantly different consumer groups were identified: participants of the
      "ambitious" group show positive attitude towards healthy diet; the "health
      conscious" cluster cares about and actively supports health and diet; and members
      of the "indifferent" cluster are less interested and do not make a remarkable
      effort for their healthy diet. CONCLUSIONS: Results of the questionnaire survey
      pointed out the importance of targeted information to relevant consumer groups,
      as well as the importance of popularization of accurate and reliable information
      sources. Furthermore, presentation and popularization of cost-effective healthy
      nutrition are of outstanding importance, especially for consumers in need (e.g.
      elderly, low-income people).

PMID- 25864140
TI  - [Fatal outcome of bilateral pulmonary embolism combined with ascending
      varicophlebitis of the lower limb: case report].
AB  - The authors review the history and risk factors of thrombophlebitis of the lower
      limb, and describe the main points of surgical and conservative treatment of
      varicophlebitis. They present the case of a 71-year-old woman who had ascending
      varicophlebitis and bilateral pulmonary embolism. The authors draw attention to
      important points: patients must be followed after phlebitis of the lower limb,
      and their thrombotic factors must be examined to prevent the new thromboembolic
      events.

PMID- 25864141
TI  - [Actors of journal publishing in the social and medical sciences].
AB  - Journals published by universities take up a modest part of the scientific
      literature at the moment, but there are several signs and even more reasons to
      believe that their significance is rising. Recently, the most significant
      increase can be detected in social sciences. The top list of university rankings
      based on journal publishing activity brings into the forefront - beside some
      obvious favorites (Oxford, Cambridge, Chicago) - some less expected universities,
      as well.

PMID- 25864142
TI  - [Markusovszky's Kesmark - Markusovszky of Kesmark].

PMID- 25864144
TI  - Persistent left atrial remodeling after catheter ablation for non-paroxysmal
      atrial fibrillation is associated with very late recurrence.
AB  - BACKGROUND: This study aimed to evaluate the association between left atrial (LA)
      structural remodeling and very late recurrence [VLR; initial recurrence >12
      months after catheter ablation (CA)] after successful CA for non-paroxysmal
      atrial fibrillation (AF). METHODS: We retrospectively evaluated 63 patients who
      underwent initial, single ablation for drug-refractory persistent or long
      standing persistent AF and those who had no recurrence in the first year after
      CA. We followed patients for a mean of 3.2+/-1.5 years and divided them into VLR
      and no-recurrence (NR) groups. Before and 3 months after ablation, all patients
      were subjected to 64-slice multidetector computed tomography scanning to estimate
      LA volume, including maximum and minimum volume during the cardiac cycle (LAMaxV
      and LAMinV, respectively), and the LA emptying fraction. RESULTS: VLR occurred in
      21 patients. The reduction rate of LAMaxV after CA was significantly larger in
      the NR group than in the VLR group (25+/-19% vs. 5+/-18%, p=0.0002). Receiver
      operating characteristic analysis was performed to determine the best cut-off
      values in the prediction of VLR. The highest area-under curve was obtained with
      post-CA LAMinV [0.828 (95% confidence interval, 0.712-0.912), p<0.0001], with a
      best cut-off value of 44mL (sensitivity 81.0%, specificity 81.0%). CONCLUSIONS:
      Persistent LA structural remodeling after initially successful CA for non
      paroxysmal AF may be an important risk factor for VLR.

PMID- 25864145
TI  - Genetic polymorphism of 21 non-CODIS STR loci for Han population in Hunan
      Province, China.

PMID- 25864146
TI  - Joint-position sense is altered by football pre-participation warm-up exercise
      and match induced fatigue.
AB  - BACKGROUND: The demands to which football players are exposed during the match
      may augment the risk of injury by decreasing the sense of joint position. This
      study aimed to assess the effect of pre-participation warm-up and fatigue induced
      by an official football match on the knee-joint-position sense of football
      players. METHODS: Fourteen semi-professional male football players (mean age:
      25.9+/-4.6 years old) volunteered in this study. The main outcome measures were
      rate of perceived exertion and knee-joint-position sense assessed at rest,
      immediately after a standard warm-up (duration 25 min), and immediately after a
      competitive football match (90 minutes duration). RESULTS: Perceived exertion
      increased significantly from rest to the other assessments (rest: 8.6+/-2.0;
      after warm-up: 12.1+/-2.1; after football match: 18.5+/-1.3; p<0.001). Compared
      to rest, absolute angular error decreased significantly after the warm-up (4.1
      degrees +/-2.2 degrees  vs. 2.0 degrees +/-1.0 degrees ; p=0.0045). After the
      match, absolute angular error (8.7 degrees +/-3.8 degrees ) increased
      significantly comparatively to both rest (p=0.001) and the end of warm-up
      (p<0.001). Relative error showed directional bias with an underestimation of the
      target position, which was higher after the football match compared to both rest
      (p<0.001) and after warm-up (p<0.001). CONCLUSIONS: The results indicate that
      knee-joint-position sense acuity was increased by pre-participation warm-up
      exercise and was decreased by football match-induced fatigue. CLINICAL RELEVANCE:
      Warm-up exercises could contribute to knee injury prevention, whereas the
      deleterious effect of match-induced fatigue on the sensorimotor system could
      ultimately contribute to knee instability and injury.

PMID- 25864147
TI  - Multiple early victimization experiences as a pathway to explain physical health
      disparities among sexual minority and heterosexual individuals.
AB  - Prior research shows that health disparities exist between sexual minority and
      heterosexual individuals. We extend the literature by testing if the higher
      prevalence of childhood victimization experienced by sexual minority individuals
      accounts for lifetime health disparities. Heterosexual (n = 422) and sexual
      minority (n = 681) participants were recruited on-line in North America.
      Respondents completed surveys about their childhood victimization experiences
      (i.e., maltreatment by adults and peer victimization) and lifetime physician
      diagnosed physical health conditions. Results showed that sexual minority
      individuals experienced higher prevalence of childhood victimization and lifetime
      physical health problems than heterosexuals. Mediation analyses indicated that
      maltreatment by adults and peer bullying explained the health disparities between
      sexual minority individuals and heterosexuals. This study is the first to show
      that multiple childhood victimization experiences may be one pathway to explain
      lifetime physical health disparities. Intervention programs reducing the
      perpetration of violence against sexual minority individuals are critical to
      reduce health care needs related to victimization experiences. 

PMID- 25864148
TI  - Competing conceptualizations of decent work at the intersection of health, social
      and economic discourses.
AB  - According to the International Labour Organization (ILO), decent work is critical
      to economic and social progress and well-being. The ILO's Decent Work Agenda
      outlines four directions (creating jobs, guaranteeing rights at work, extending
      social protection, promoting social dialogue) (ILO, 2015). While the Agenda's
      existence may imply consensus about its meaning, we contend that several
      conceptualizations of decent work exist in the global policy arena. Different
      institutional perspectives must be negotiated, and political, economic, social
      and health considerations balanced in its pursuit. This paper reports findings
      from a critical discourse analysis of 10 policy texts that aimed to reveal
      different health, economic, and social claims about decent work and how these are
      shaped by the work policy agendas of the ILO, World Health Organization, and
      World Bank. Themes emerging from the discourse analysis include the: challenges
      and realities of promoting "one" agenda; complex intersection between decent
      work, health and health equity concepts; emphasis on economic and pro-market
      interests versus the social dimensions of work; and, relative emphasis on
      individual versus collective responsibility for decent work. To our knowledge,
      this is a first attempt to contrast different conceptualizations of decent work
      involving these institutions. Our findings suggest that decent work is a
      contested notion, and that more than one "agenda" is operating in the face of
      vested institutional interests. Broader discourses are contributing to a
      reframing of decent work in economic, social and/or health terms and these are
      impacting which dimensions of work are taken up in policy texts over others.
      Results show how the language of economics acts as a disciplinary and regulatory
      power and its role as a normalizing discourse. We call for research that deepens
      understanding of how a social, economic and health phenomenon like work is
      discursively re-interpreted through different global institutional interests. 

PMID- 25864149
TI  - 'It's like having a physician in your pocket!' A critical analysis of self
      diagnosis smartphone apps.
AB  - More than 100,000 mobile phone software applications ('apps') have been designed
      for the dissemination of health and medical information and healthcare and public
      health initiatives. This article presents a critical analysis of self-diagnosis
      smartphone apps directed at lay people that were available on the Apple App Store
      and Google Play in mid-April 2014. The objective of the analysis is to contribute
      to the sociology of diagnosis and to critical digital health studies by
      investigating the phenomenon of digitised diagnosis via apps. We adopted a
      perspective that views apps as sociocultural artefacts. Our analysis of self
      diagnosis apps suggests that they inhabit a contested and ambiguous site of
      meaning and practice. We found that app developers combined claims to medical
      expertise in conjunction with appeals to algorithmic authority to promote their
      apps to potential users. While the developers also used appeals to patient
      engagement as part of their promotional efforts, these were undermined by routine
      disclaimers that users should seek medical advice to effect a diagnosis. More
      research is required to investigate how lay people are negotiating the use of
      these apps, the implications for privacy of their personal data and the possible
      effects on the doctor-patient relationship and medical authority in relation to
      diagnosis. 

PMID- 25864150
TI  - Participation and diffusion effects of a peer-intervention for HIV prevention
      among adults in rural Malawi.
AB  - This paper examines whether a peer group intervention that reduced self-reported
      risky behaviors for rural adults in Malawi also had impacts on non-participants
      in the same communities. We randomly assigned two districts to the intervention
      and control conditions, and conducted surveys at baseline and 18 months post
      intervention using unmatched independent random samples of intervention and
      control communities in 2003-2006. The six-session peer group intervention was
      offered to same-gender groups by trained volunteers. In this analysis, we divided
      the post-intervention sample into three exposure groups: 243 participants and 170
      non-participants from the intervention district (total n = 415) and 413 control
      individuals. Controlling for demographics and participation, there were
      significant favorable diffusion effects on five partially overlapping behavioral
      outcomes: partner communication, ever used condoms, unprotected sex, recent HIV
      test, and a community HIV prevention index. Non-participants in the intervention
      district had more favorable outcomes on these behaviors than survey respondents
      in the control district. One behavioral outcome, community HIV prevention, showed
      both participation and diffusion effects. Participating in the intervention had a
      significant effect on six psychosocial outcomes: HIV knowledge (two measures),
      hope, condom attitudes, and self-efficacy for community HIV prevention and for
      safer sex; there were no diffusion effects. This pattern of results suggests that
      the behavioral changes promoted in the intervention spread to others in the same
      community, most likely through direct contact between participants and non
      participants. These findings support the idea that diffusion of HIV-related
      behavior changes can occur for peer group interventions in communities, adding to
      the body of research supporting diffusion of innovations theory as a robust
      approach to accelerating change. If diffusion occurs, peer group intervention may
      be more cost-effective than previously realized. Wider implementation of peer
      group interventions can help meet the global goal of reducing new HIV infections.

PMID- 25864151
TI  - Cultural Health Capital on the margins: Cultural resources for navigating
      healthcare in communities with limited access.
AB  - Communities struggling with access to healthcare in the U.S. are often considered
      to be disadvantaged and lacking in resources. Yet, these communities develop and
      nurture valuable strategies for healthcare access that are underrecognized by
      health scholars. Combining medical sociology and critical race theory
      perspectives on cultural capital, this paper examines the health-relevant
      cultural resources, or Cultural Health Capital, in South Texas Mexican American
      border communities. Ethnographic data collected during 2011-2013 in Cameron and
      Hidalgo counties on the U.S.-Mexico border provide empirical evidence for
      expanding existing notions of health-relevant cultural capital. These Mexican
      American communities use a range of cultural resources to manage healthcare
      exclusion and negotiate care in alternative healthcare spaces like community
      clinics, flea markets and Mexican pharmacies. Navigational, social, familial, and
      linguistic skills and knowledge are used to access doctors and prescription drugs
      in these spaces despite social barriers to mainstream healthcare (e.g. cost,
      English language skills, etc.). Cultural capital used in marginalized communities
      to navigate limited healthcare options may not always fully counteract healthcare
      exclusion. Nevertheless, recognizing the cultural resources used in Mexican
      American communities to facilitate healthcare challenges deficit views and yields
      important findings for policymakers, healthcare providers, and advocates seeking
      to capitalize on community resources to improve healthcare access. 

PMID- 25864152
TI  - Paying people to eat or not to eat? Carryover effects of monetary incentives on
      eating behaviour.
AB  - There is no evidence comparing head-to-head the effects of monetary incentives to
      act and to abstain from acting on behaviour. We present an experiment, conducted
      between June and September 2012, that directly compares the effects of those two
      different monetary incentive schemes on eating behaviour: we evaluate incentives
      to eat against incentives not to eat. A large number of participants (n = 353)
      had bowls of sweets next to them while they watched different videos over two
      experimental sessions that were two days apart. Sweets eating was monitored and
      monetary incentives to eat or not to eat were introduced during one of the videos
      for participants randomly allocated to these conditions. Our results show that,
      while both types of incentives were effective in changing sweets-eating behaviour
      when they were in place, only incentives not to eat had significant carryover
      effects after they were removed. Those effects were still significant two days
      after the monetary incentives had been eliminated. We also present some
      additional results on personality and health-related variables that shed further
      light on these effects. Overall, our study shows that incentives not to eat can
      be more effective in producing carryover effects on behaviour in domains like the
      one explored here. 

PMID- 25864153
TI  - Chemical characterization of atmospheric particles and source apportionment in
      the vicinity of a steelmaking industry.
AB  - The objective of this work was to provide a chemical characterization of
      atmospheric particles collected in the vicinity of a steelmaking industry and to
      identify the sources that affect PM10 levels. A total of 94 PM samples were
      collected in two sampling campaigns that occurred in February and June/July of
      2011. PM2.5 and PM2.5-10 were analyzed for a total of 22 elements by Instrumental
      Neutron Activation Analysis and Particle Induced X-ray Emission. The
      concentrations of water soluble ions in PM10 were measured by Ion Chromatography
      and Indophenol-Blue Spectrophotometry. Positive Matrix Factorization receptor
      model was used to identify sources of particulate matter and to determine their
      mass contribution to PM10. Seven main groups of sources were identified: marine
      aerosol identified by Na and Cl (22%), steelmaking and sinter plant represented
      by As, Cr, Cu, Fe, Ni, Mn, Pb, Sb and Zn (11%), sinter plant stack identified by
      NH4(+), K and Pb (12%), an unidentified Br source (1.8%), secondary aerosol from
      coke making and blast furnace (19%), fugitive emissions from the handling of raw
      material, sinter plant and vehicles dust resuspension identified by Al, Ca, La,
      Si, Ti and V (14%) and sinter plant and blast furnace associated essentially with
      Fe and Mn (21%). 

PMID- 25864154
TI  - Current status, between-year comparisons and maternal transfer of
      organohalogenated compounds (OHCs) in Arctic char (Salvelinus alpinus) from
      Bjornoya, Svalbard (Norway).
AB  - High levels of organohalogenated compounds (OHCs) have been found in Arctic char
      from Lake Ellasjoen at Bjornoya (Svalbard, Norway) compared to char from other
      arctic lakes. The first aim of the study was to investigate the OHC status,
      contaminant profile, and partitioning of OHCs between muscle and ovary tissue in
      spawning female char from the high-polluted Lake Ellasjoen and the low-polluted
      Lake Laksvatn. The second aim was to investigate if OHC levels in muscle tissue
      have changed over time. Between-lake comparisons show that the muscle levels
      (lipid weight) of hexachlorobenzene (HCB), chlordanes (?CHLs), mirex,
      dichlorodiphenyltrichloroethanes (?DDTs) and polychlorinated biphenyls (?PCBs)
      were up to 36 times higher in char from Ellasjoen than in Laksvatn, and confirm
      that the char from Ellasjoen are still heavily exposed compared to char from
      neighboring lake. A higher proportion of persistent OHCs were found in Ellasjoen
      compared to Laksvatn, while the proportion of the less persistent OHCs was
      highest in Laksvatn. A between-year comparison of OHC levels (i.e., HCB, DDTs,
      PCBs) in female and male char shows higher levels of HCB in female char from
      Ellasjoen in 2009/2012 compared to in 1999/2001. No other between-year
      differences in OHC levels were found. Due to small study groups, findings
      associated with between-year differences in OHC levels should be interpreted with
      caution. OHCs accumulate in the lipid rich ovaries of spawning females, resulting
      in up to six times higher levels of OHCs in ovaries compared to in muscle (wet
      weight). The toxic equivalent (TEQ)-value for the dioxin-like PCBs (PCB-105 and 
      118) in ovaries of the Ellasjoen char exceeded levels associated with increased
      egg mortality in rainbow trout (Oncorhynchus mykiss). Hence, we suggest that
      future studies should focus on the reproductive health and performance abilities
      of the high-exposed population of char inhabiting Lake Ellasjoen. 

PMID- 25864155
TI  - Carbonaceous aerosols and pollutants over Delhi urban environment: Temporal
      evolution, source apportionment and radiative forcing.
AB  - Particulate matter (PM2.5) samples were collected over Delhi, India during
      January to December 2012 and analysed for carbonaceous aerosols and inorganic
      ions (SO4(2-) and NO3(-)) in order to examine variations in atmospheric
      chemistry, combustion sources and influence of long-range transport. The PM2.5
      samples are measured (offline) via medium volume air samplers and analysed
      gravimetrically for carbonaceous (organic carbon, OC; elemental carbon, EC)
      aerosols and inorganic ions (SO4(2-) and NO3(-)). Furthermore, continuous
      (online) measurements of PM2.5 (via Beta-attenuation analyser), black carbon (BC)
      mass concentration (via Magee scientific Aethalometer) and carbon monoxide (via
      CO-analyser) are carried out. PM2.5 (online) range from 18.2 to 500.6MUgm(-3)
      (annual mean of 124.6+/-87.9MUgm(-3)) exhibiting higher night-time (129.4MUgm(
      3)) than daytime (103.8MUgm(-3)) concentrations. The online concentrations are
      38% and 28% lower than the offline during night and day, respectively. In
      general, larger night-time concentrations are found for the BC, OC, NO3(-)and
      SO4(2-), which are seasonally dependent with larger differences during late post
      monsoon and winter. The high correlation (R(2)=0.74) between OC and EC along with
      the OC/EC of 7.09 (day time) and 4.55 (night-time), suggest significant influence
      of biomass-burning emissions (burning of wood and agricultural waste) as well as
      secondary organic aerosol formation during daytime. Concentrated weighted
      trajectory (CWT) analysis reveals that the potential sources for the carbonaceous
      aerosols and pollutants are local emissions within the urban environment and
      transported smoke from agricultural burning in northwest India during post
      monsoon. BC radiative forcing estimates result in very high atmospheric heating
      rates (~1.8-2.0Kday(-1)) due to agricultural burning effects during the 2012 post
      monsoon season. 

PMID- 25864156
TI  - Analysis of 24 Y chromosomal STR haplotypes in a Chinese Han population sample
      from Henan Province, Central China.
AB  - We analyzed haplotypes for 24 Y chromosomal STRs (Y-STRs), including 17 Yfiler
      loci (DYS19, DYS385a/b, DYS389I/II, DYS390, DYS391, DYS392, DYS393, DYS437,
      DY438, DYS439, DYS448, DYS456, DYS458, DYS635 and Y-GATA-H4) and 7 additional
      STRs (DYS388, DYS444, DYS447, DYS449, DYS522 and DYS527a/b) in 1100 unrelated
      Chinese Han individuals from Henan Province using AGCU Y24 STR kit systems. The
      calculated average gene diversity (GD) values ranged from 0.4105 to 0.9647 for
      the DYS388 and DYS385a/b loci, respectively. The discriminatory capacity (DC) was
      72.91% with 802 observed haplotypes using 17 Yfiler loci, by the addition of 7 Y
      STRs to the Yfiler system, the DC was increased to 79.09% while showing 870
      observed haplotypes. Among the additional 7 Y-STRs, DYS449, DYS527a/b, DYS444 and
      DYS522 were major contributors to enhancing discrimination. In the analysis of
      molecular variance, the Henan Han population clustered with Han origin
      populations and showed significant differences from other Non-Han populations. In
      the present study, we report 24 Y-STR population data in Henan Han population,
      and we emphasize the need for adding additional markers to the commonly used 17
      Yfiler loci to achieve more improved discriminatory capacity in a population with
      low genetic diversity. 

PMID- 25864157
TI  - Assessing the impact of common forensic presumptive tests on the ability to
      obtain results using a novel rapid DNA platform.
AB  - The rise of DNA evidence to the forefront of forensic science has led to high
      sample numbers being submitted for profiling by investigators to casework
      laboratories: bottleneck effects are often seen resulting in slow turnaround
      times and sample backlog. The ParaDNA((r)) Screening and Intelligence Tests have
      been designed to guide investigators on the viability of potential sources of DNA
      allowing them to determine which samples should be sent for full DNA analysis.
      Both tests are designed to augment the arsenal of available forensic tests for
      end users and be used concurrently to those commonly available. Therefore,
      assessing the impact that common forensic tests have on such novel technology is
      important to measure. The systems were tested against various potential
      inhibitors to which samples may be exposed as part of the investigative process.
      Presumptive test agents for biological materials (blood, semen and saliva) and
      those used as fingerprint enhancement agents were both used. The Screening Test
      showed a drop in performance following application of aluminium powder and
      cyanoacrylate (CNA) on fingerprints samples; however this drop in performance was
      not replicated with high template DNA. No significant effect was observed for any
      agent using the Intelligence Test. Therefore, both tests stand up well to the
      chemical agents applied and can be used by investigators with confidence that
      system performance will be maintained. 

PMID- 25864158
TI  - Re: Adrian Pilatz, Hamid Hossain, Rolf Kaiser, et al. Acute epididymitis
      revisited: impact of molecular diagnostics on etiology and contemporary guideline
      recommendations. Eur Urol 2015;68:428-35.

PMID- 25864159
TI  - Reply to Kevin Lu's letter to the editor re: Arun A. Azad, Bernhard J. Eigl, Raya
      Leibowitz-Amit, et al. outcomes with abiraterone acetate in metastatic castration
      resistant prostate cancer patients who have poor performance status. Eur Urol
      2015;67:441-7.

PMID- 25864160
TI  - A genetic risk score of 45 coronary artery disease risk variants associates with
      increased risk of myocardial infarction in 6041 Danish individuals.
AB  - BACKGROUND: In Europeans, 45 genetic risk variants for coronary artery disease
      (CAD) have been identified in genome-wide association studies. We constructed a
      genetic risk score (GRS) of these variants to estimate the effect on incidence
      and clinical predictability of myocardial infarction (MI) and CAD. METHODS:
      Genotype was available from 6041 Danes. An unweighted GRS was constructed by
      making a summated score of the 45 known genetic CAD risk variants. Registries
      provided information (mean follow-up = 11.6 years) on CAD (n = 374) and MI (n =
      124) events. Cox proportional hazard estimates with age as time scale was
      adjusted for sex, BMI, type 2 diabetes mellitus and smoking status. Analyses were
      also stratified either by sex or median age (below or above 45 years of age). We
      estimated GRS contribution to MI prediction by assessing net reclassification
      index (NRI) and integrated discrimination improvement (IDI) added to the European
      SCORE for 10-year MI risk prediction. RESULTS: The GRS associated significantly
      with risk of incident MI (allele-dependent hazard ratio (95%CI): 1.06 (1.02
      1.11), p = 0.01) but not with CAD (p = 0.39). Stratification revealed association
      of GRS with MI in men (1.06 (1.01-1.12), p = 0.02) and in individuals above the
      median of 45.11 years of age (1.06 (1.00-1.12), p = 0.03). There was no
      interaction between GRS and gender (p = 0.90) or age (p = 0.83). The GRS improved
      neither NRI nor IDI. CONCLUSION: The GRS of 45 GWAS identified risk variants
      increase the risk of MI in a Danish cohort. The GRS did not improve NRI or IDI
      beyond the performance of conventional European SCORE risk factors.

PMID- 25864161
TI  - Ethnic differences in the association between lipid metabolism genes and lipid
      levels in black and white South African women.
AB  - OBJECTIVE: Dyslipidaemia can lead to the development of atherosclerosis and
      cardiovascular disease (CVD), however its prevalence has been shown to differ
      between ethnic groups in South Africa (SA). Therefore the aim of this study was
      to investigate ethnic differences in the association between serum lipid levels
      and polymorphisms within genes involved in lipid metabolism in black and white SA
      women. METHODS: In a convenient sample of 234 white and 209 black SA women of
      Xhosa ancestry, body composition (DXA) and fasting serum lipids were measured.
      Participants were genotyped for the cholesteryl ester transfer protein (CETP,
      rs708272, B1/B2), lipoprotein lipase (LPL, rs328, S/X), hepatic lipase (LIPC,
      rs1800588, C/T) and proprotein convertase subtilisin/kexin type 9 (PCSK9,
      rs28362286, C/X) polymorphisms. RESULTS: Compared to white women, black women had
      lower concentrations of serum total cholesterol (TC, P < 0.001), low density
      lipoprotein cholesterol (LDL-C, P < 0.001), high density lipoprotein cholesterol
      (HDL-C, P < 0.001) and triglycerides (TG, P < 0.001). There were significant
      differences in the genotype and allele frequency distributions between black and
      white women for the LPL S/X (P < 0.001), PCSK9 C679X (P = 0.002) and LIPC 514C/T
      (P < 0.001) polymorphisms. In black women only, there were genotype effects on
      serum lipid levels. Specifically, women with the LPL SX genotype had lower TC and
      LDL-C and higher HDL-C concentrations than those with the SS genotype and women
      with the CETP B2 allele had lower LDL-C concentrations than those with the B1B1
      genotype. CONCLUSION: Polymorphisms within the LPL and CETP genes were associated
      with a more protective lipid profile in black, but not white SA women. This
      supports the hypothesis that the more favorable lipid profile of black compared
      to white SA women is associated with polymorphisms in lipid metabolism genes,
      specifically the LPL and CETP genes.

PMID- 25864162
TI  - High daily insulin exposure in patients with type 2 diabetes is associated with
      increased risk of cardiovascular events.
AB  - AIMS: Intensive glucose control, often involving insulin treatment, failed to
      improve cardiovascular outcomes in several clinical trials. Observational studies
      reported an association between insulin use and cardiovascular disease (CVD)
      risk. It has therefore been suggested that insulin adversely affects CVD risk. To
      investigate the feasibility of this hypothesis, we studied the association
      between insulin dose and CVD risk in type 2 diabetes. METHODS: A case-control
      study was conducted of new users of oral antidiabetics who were prescribed
      insulin, using the Dutch Pharmo database. Cases were hospitalized for a
      cardiovascular event (CVE) and matched 1:2 to patients who were not hospitalized
      for a CVE, by sex, age, duration of diabetes and type of oral antidiabetic.
      Patients were divided into tertiles according to mean daily insulin dose.
      Conditional logistic regression analyses were used to explore the association
      between insulin exposure and CVE risk. RESULTS: We included 836 patients (517
      (62%) male, mean age 66 years). After adjusting for available potential
      confounders, including HbA1c and triglycerides, insulin exposure was positively
      related to CVE risk (odds ratios for high (>=53.0 U/day) and intermediate (24.3
      52.9 U/day) vs. low exposure (<=24.2 U/day): 3.00 [95% confidence interval (CI)
      1.70 to 5.28] and 2.03 [95% CI 1.17 to 3.52]. CONCLUSION: Our findings are in
      line with the suggestion that high-dose insulin therapy adversely affects CVD
      risk, but need to be interpreted with caution due to the observational nature of
      the study. The role of particularly high-dose insulin in the progression of CVD
      warrants further investigation.

PMID- 25864163
TI  - Lyme disease: a case report of a 17-year-old male with fatal Lyme carditis.
AB  - Lyme disease is a systemic infection commonly found in the northeastern, mid
      Atlantic, and north-central regions of the United States. Of the many systemic
      manifestations of Lyme disease, cardiac involvement is uncommon and rarely causes
      mortality. We describe a case of a 17-year-old adolescent who died unexpectedly
      after a 3-week viral-like syndrome. Postmortem examination was remarkable for
      diffuse pancarditis characterized by extensive infiltrates of lymphocytes and
      focal interstitial fibrosis. In the cardiac tissue, Borrelia burgdorferi was
      identified via special stains, immunohistochemistry, and polymerase chain
      reaction. The findings support B. burgdorferi as the causative agent for his
      fulminant carditis and that the patient suffered fatal Lyme carditis. Usually,
      Lyme carditis is associated with conduction disturbances and is a treatable
      condition. Nevertheless, few cases of mortality have been reported in the
      literature. Here, we report a rare example of fatal Lyme carditis in an
      unsuspected patient.

PMID- 25864164
TI  - A new machine learning approach for predicting the response to anemia treatment
      in a large cohort of End Stage Renal Disease patients undergoing dialysis.
AB  - Chronic Kidney Disease (CKD) anemia is one of the main common comorbidities in
      patients undergoing End Stage Renal Disease (ESRD). Iron supplement and
      especially Erythropoiesis Stimulating Agents (ESA) have become the treatment of
      choice for that anemia. However, it is very complicated to find an adequate
      treatment for every patient in each particular situation since dosage guidelines
      are based on average behaviors, and thus, they do not take into account the
      particular response to those drugs by different patients, although that response
      may vary enormously from one patient to another and even for the same patient in
      different stages of the anemia. This work proposes an advance with respect to
      previous works that have faced this problem using different methodologies
      (Machine Learning (ML), among others), since the diversity of the CKD population
      has been explicitly taken into account in order to produce a general and reliable
      model for the prediction of ESA/Iron therapy response. Furthermore, the ML model
      makes use of both human physiology and drug pharmacology to produce a model that
      outperforms previous approaches, yielding Mean Absolute Errors (MAE) of the
      Hemoglobin (Hb) prediction around or lower than 0.6 g/dl in the three countries
      analyzed in the study, namely, Spain, Italy and Portugal.

PMID- 25864165
TI  - A software platform for phase contrast x-ray breast imaging research.
AB  - PURPOSE: To present and validate a computer-based simulation platform dedicated
      for phase contrast x-ray breast imaging research. METHODS: The software platform,
      developed at the Technical University of Varna on the basis of a previously
      validated x-ray imaging software simulator, comprises modules for object creation
      and for x-ray image formation. These modules were updated to take into account
      the refractive index for phase contrast imaging as well as implementation of the
      Fresnel-Kirchhoff diffraction theory of the propagating x-ray waves. Projection
      images are generated in an in-line acquisition geometry. To test and validate the
      platform, several phantoms differing in their complexity were constructed and
      imaged at 25 keV and 60 keV at the beamline ID17 of the European Synchrotron
      Radiation Facility. The software platform was used to design computational
      phantoms that mimic those used in the experimental study and to generate x-ray
      images in absorption and phase contrast modes. RESULTS: The visual and
      quantitative results of the validation process showed an overall good correlation
      between simulated and experimental images and show the potential of this platform
      for research in phase contrast x-ray imaging of the breast. The application of
      the platform is demonstrated in a feasibility study for phase contrast images of
      complex inhomogeneous and anthropomorphic breast phantoms, compared to x-ray
      images generated in absorption mode. CONCLUSIONS: The improved visibility of
      mammographic structures suggests further investigation and optimisation of phase
      contrast x-ray breast imaging, especially when abnormalities are present. The
      software platform can be exploited also for educational purposes.

PMID- 25864166
TI  - Determining the bistability parameter ranges of artificially induced lac operon
      using the root locus method.
AB  - This paper employs the root locus method to conduct a detailed investigation of
      the parameter regions that ensure bistability in a well-studied gene regulatory
      network namely, lac operon of Escherichia coli (E. coli). In contrast to previous
      works, the parametric bistability conditions observed in this study constitute a
      complete set of necessary and sufficient conditions. These conditions were
      derived by applying the root locus method to the polynomial equilibrium equation
      of the lac operon model to determine the parameter values yielding the multiple
      real roots necessary for bistability. The lac operon model used was defined as an
      ordinary differential equation system in a state equation form with a rational
      right hand side, and it was compatible with the Hill and Michaelis-Menten
      approaches of enzyme kinetics used to describe biochemical reactions that govern
      lactose metabolism. The developed root locus method can be used to study the
      steady-state behavior of any type of convergent biological system model based on
      mass action kinetics. This method provides a solution to the problem of analyzing
      gene regulatory networks under parameter uncertainties because the root locus
      method considers the model parameters as variable, rather than fixed. The
      obtained bistability ranges for the lac operon model parameters have the
      potential to elucidate the appearance of bistability for E. coli cells in in vivo
      experiments, and they could also be used to design robust hysteretic switches in
      synthetic biology. 

PMID- 25864167
TI  - Role of humic substances in promoting autotrophic growth in nitrate-dependent
      iron-oxidizing bacteria.
AB  - Nitrate-dependent iron oxidation was discovered in 1996 and has been reported
      from various environments ever since. To date, despite the widespread nature of
      this process, all attempts to cultivate chemolithoautotrophic nitrate-dependent
      iron oxidizers have been unsuccessful. The present study was focused on
      understanding the influence of natural chelating agents of iron, like humic
      substances, on the culturability, activity, and enumeration, of these
      microorganisms. Pure culture studies conducted with Thiobacillus denitrificans
      showed a constant increase in cell mass with a corresponding nitrate-dependent
      iron oxidation activity only when Fe(II) was provided together with humic
      substances, compared to no growth in control incubations without humic
      substances. The presence of a relatively strong chelating agent, such as EDTA,
      inhibited the growth of Thiobacillus denitrificans. It was concluded that complex
      formation between humic substances and iron was required for
      chemolithoautotrophic nitrate-dependent iron oxidation. Most probable number
      enumerations showed that numbers of chemolithoautotrophic nitrate-dependent iron
      oxidizing bacteria were one to three orders of magnitude higher in the presence
      of humic substances compared to media without. Similar results were obtained when
      potential nitrate-dependent iron oxidation activity was determined in soil
      samples. In summary, this study showed that humic substances significantly
      enhanced the growth and activity of autotrophic nitrate-dependent iron-oxidizing
      microorganisms, probably by chelation of iron. 

PMID- 25864168
TI  - Comments on: "A polyphasic approach leading to the revision of the genus
      Planktothrix (Cyanobacteria) and its type species, P. agardhii, and proposal for
      integrating the emended valid botanical taxa, as well as three new species,
      Planktothrix paucivesiculata sp. nov.(ICNP), Planktothrix tepida sp. nov.(ICNP),
      and Planktothrix serta sp. nov.(ICNP), as genus and species names with
      nomenclature standing under the ICNP," by V. Gaget, M. Welker, R. Rippka, and N.
      Tandeau de Marsac, Syst. Appl. Microbiol. (2015),
      http://dx.doi.org/10.1016/j.syapm.2015.02.004.

PMID- 25864169
TI  - New approaches to establish genetic causality.
AB  - Cardiovascular medicine has evolved rapidly in the era of genomics with many
      diseases having primary genetic origins becoming the subject of intense
      investigation. The resulting avalanche of information on the molecular causes of
      these disorders has prompted a revolution in our understanding of disease
      mechanisms and provided new avenues for diagnoses. At the heart of this
      revolution is the need to correctly classify genetic variants discovered during
      the course of research or reported from clinical genetic testing. This review
      will address current concepts related to establishing the cause and effect
      relationship between genomic variants and heart diseases. A survey of general
      approaches used for functional annotation of variants will also be presented. 

PMID- 25864170
TI  - Use of genetic testing to identify sudden cardiac death syndromes.
AB  - Sudden cardiac death (SCD) is a leading cause of mortality worldwide. Although
      coronary artery disease remains the most common substrate for SCD, primary
      cardiac genetic diseases, presenting with or without structural heart
      abnormalities, play a significant role. In the last 30 years, the study of large
      family pedigrees allowed the discovery of causative genes unveiling the genetic
      basis of diseases such as primary cardiomyopathies and arrhythmia syndromes,
      which are known to increase the risk of SCD. However, recent technological
      advancement with the ability to perform massive parallel sequencing and analyze
      the entire genome has uncovered a higher level of complexity in the genetic
      predisposition for cardiac diseases, which are usually characterized by Mendelian
      inheritance patterns. Clinical genetic testing, historically shaped around a
      monogenic Mendelian disorder paradigm, is now facing the challenge to adopt and
      adapt to a more complex model in which a significant portion of subjects may
      present with multi-allelic inheritance involving additional genes that could
      modulate the severity and type of disease-related phenotypes. Here, we will try
      to provide a viewpoint that will hopefully foster further debate in the field. 

PMID- 25864171
TI  - Comparison of [(11)C]choline Positron Emission Tomography With T2- and Diffusion
      Weighted Magnetic Resonance Imaging for Delineating Malignant Intraprostatic
      Lesions.
AB  - PURPOSE: The purpose of this study was to compare the accuracy of [(11)C]choline
      positron emission tomography (CHOL-PET) with that of the combination of T2
      weighted and diffusion-weighted (T2W/DW) magnetic resonance imaging (MRI) for
      delineating malignant intraprostatic lesions (IPLs) for guiding focal therapies
      and to investigate factors predicting the accuracy of CHOL-PET. METHODS AND
      MATERIALS: This study included 21 patients who underwent CHOL-PET and T2W/DW MRI
      prior to radical prostatectomy. Two observers manually delineated IPL contours
      for each scan, and automatic IPL contours were generated on CHOL-PET based on
      varying proportions of the maximum standardized uptake value (SUV). IPLs
      identified on prostatectomy specimens defined reference standard contours. The
      imaging-based contours were compared with the reference standard contours using
      Dice similarity coefficient (DSC), and sensitivity and specificity values.
      Factors that could potentially predict the DSC of the best contouring method were
      analyzed using linear models. RESULTS: The best automatic contouring method, 60%
      of the maximum SUV (SUV60) , had similar correlations (DSC: 0.59) with the manual
      PET contours (DSC: 0.52, P=.127) and significantly better correlations than the
      manual MRI contours (DSC: 0.37, P<.001). The sensitivity and specificity values
      were 72% and 71% for SUV60; 53% and 86% for PET manual contouring; and 28% and
      92% for MRI manual contouring. The tumor volume and transition zone pattern could
      independently predict the accuracy of CHOL-PET. CONCLUSIONS: CHOL-PET is superior
      to the combination of T2W/DW MRI for delineating IPLs. The accuracy of CHOL-PET
      is insufficient for gland-sparing focal therapies but may be accurate enough for
      focal boost therapies. The transition zone pattern is a new classification that
      may predict how well CHOL-PET delineates IPLs.

PMID- 25864173
TI  - Quaternary ammonium disinfectants: microbial adaptation, degradation and ecology.
AB  - Disinfectants play an important role in maintaining acceptable health standards
      by significantly reducing microbial loads as well as reducing, if not
      eliminating, pathogens. This review focuses on quaternary ammonium compounds
      (QACs), a widely used class of organic disinfectants. Specifically, it reviews
      the occurrence, microbial adaptation, and degradation of QACs, focusing on recent
      reports on the ecology of QAC-degraders, the pathways and mechanisms of microbial
      adaptation which lead to resistance to QACs, as well as to antibiotics. With the
      help of culture-dependent and nonculture-dependent tools, as well as advanced
      analytical techniques, a better understanding of the fate and effect of QACs and
      their biotransformation products is emerging. Understanding the underlying
      mechanisms and conditions that result in QAC resistance and biodegradation will
      be instrumental in the prudent use of existing QAC formulations and foster the
      development of safer disinfectants. Development and implementation of
      (bio)technologies for the elimination of QACs from treated wastewater effluents
      will lessen adverse impacts to both humans and the environment. 

PMID- 25864172
TI  - Local failure in parameningeal rhabdomyosarcoma correlates with poor response to
      induction chemotherapy.
AB  - BACKGROUND: Local control remains a challenge in pediatric parameningeal
      rhabdomyosarcoma (PM-RMS), and survival after local failure (LF) is poor.
      Identifying patients with a high risk of LF is of great interest to clinicians.
      In this study, we examined whether tumor response to induction chemotherapy (CT)
      could predict LF in embryonal PM-RMS. METHODS: We identified 24 patients with
      embryonal PM-RMS, age 2 to 18 years, with complete magnetic resonance imaging and
      gross residual disease after surgical resection. All patients received proton
      radiation therapy (RT), median dose 50.4 GyRBE (50.4-55.8 GyRBE). Tumor size was
      measured before initial CT and before RT. RESULTS: With a median follow-up time
      of 4.1 years for survivors, LF was seen in 9 patients (37.5%). The median time
      from the initiation of CT to the start of RT was 4.8 weeks. Patients with LF had
      a similar initial (pre-CT) tumor volume compared with patients with local
      controlled (LC) (54 cm(3) vs 43 cm(3), P=.9) but a greater median volume before
      RT (pre-RT) (40 cm(3) vs 7 cm(3), P=.009) and a smaller median relative percent
      volume reduction (RPVR) in tumor size (0.4% vs 78%, P<.001). Older age (P=.05),
      larger pre-RT tumor volume (P=.03), and smaller RPVR (P=.003) were significantly
      associated with actuarial LF on univariate Cox analysis. CONCLUSIONS: Poor
      response to induction CT appears to be associated with an increased risk of LF in
      pediatric embryonal PM-RMS.

PMID- 25864174
TI  - A novel strain of porcine epidemic diarrhea virus in Vietnamese pigs.
AB  - Porcine epidemic diarrhea virus (PEDV) causes severe diarrhea and dehydration in
      suckling pigs and has caused high rates of death among piglets and substantial
      economic loss in Vietnam since 2009. To investigate the genotypes of prevailing
      PEDVs, intestinal and fecal samples from piglets from central and northern
      Vietnam were collected and analyzed. Phylogenetic analysis of the nucleotide
      sequences of complete spike genes of PEDVs from Vietnam resulted in the
      identification of two divergent groups. PEDVs (HUA-PED45 and HUA-PED47) belonged
      to the G2b group, along with Chinese, US, and Korean strains occurring at the end
      of 2010, in May 2013 and in November 2013, respectively. Six strains from the
      Quang Tri region were assigned to the G1b group, along with Chinese and US
      strains. The Vietnamese PEDVs detected in infected piglets had a nationwide
      distribution and belonged to the G2b and G1b genotypes. 

PMID- 25864175
TI  - Impact on antibody responses of B-cell-restricted transgenic expression of a
      viral gene inhibiting activation of NF-kappaB and NFAT.
AB  - In this work, we have assessed the impact in vivo of the evasion gene A238L of
      African swine fever virus, an inhibitor of both NF-kappaB- and NFAT-mediated
      transcription. The A238L gene was selectively expressed in mouse B lymphocytes
      using the promoter and enhancer sequences of the mouse Ig MU heavy chain. The IgM
      primary and IgG2b secondary serological responses and the number of splenic
      germinal centres in response to the TD antigens DNP-keyhole limpet hemocyanin and
      sheep red blood cells, respectively, were both lower in the transgenic mice,
      whereas the response to the TI type-1 and type-2 antigens DNP-Ficoll and DNP-LPS,
      respectively, were normal, except for the increased levels of IgG3 at day 14 in
      the DNP-LPS-immunized mice. Thus, it appears that neither p65 (NF-kappaB) nor
      NFAT is essential for B-cell development but, in a manner that is still unclear,
      may be relevant for their function.

PMID- 25864176
TI  - Effects of light intensity and quality on phycobiliprotein accumulation in the
      cyanobacterium Nostoc sphaeroides Kutzing.
AB  - OBJECTIVES: To assess the effects of light intensity and quality on the growth
      and phycobiliproteins (PBP) accumulation in Nostoc sphaeroides Kutzing (N.
      sphaeroides). RESULTS: Dry weights, dry matter, protein, chlorophyll and PBP
      contents were higher under 90 MUmol m(-2) s(-1) than under other intensities
      (both higher and lower). Phycocyanin and allophycocyanin increased with light
      intensity while phycoerythrin decreased. Fresh weights, protein and PBP contents
      increased at the highest rates under blue light. Red light resulted in higher
      values of dry matter, phycocyanin and chlorophyll a. CONCLUSION: White light at
      90 MUmol m(-2) s(-1) or blue light 30 MUmol m(-2) s(-1) were optimal for the
      growth and phycobiliprotein accumulation in N. sphaeroides.

PMID- 25864177
TI  - Survival and local recruitment are driven by environmental carry-over effects
      from the wintering area in a migratory seabird.
AB  - We estimated annual apparent survival rates, as well as local recruitment rates
      in different age groups and for different breeding status in the common tern
      Sterna hirundo using mark-recapture analysis on a long-term individual-based
      dataset from a breeding colony in Germany. Strong inter-annual variability in
      survival rates became apparent, especially in prospectors. Local recruitment also
      varied strongly between years and age groups. To explain these fluctuations, we
      linked survival and recruitment estimates to several environmental covariates
      expected to be limiting during the wintering period and migration, including the
      global climate indices of North Atlantic Oscillation and Southern Oscillation,
      fish abundance indices, and marine primary productivity in the West African
      wintering area. Contrary to expectations, global indices did not seem to be
      linked strongly to vital rates. Results showed that primary productivity had the
      strongest effect on annual survival, especially in young and inexperienced
      individuals. Primary productivity in the wintering area was also strongly
      associated with the probability of recruitment in the following breeding season,
      indicating that conditions during winter can have carry-over effects on the life
      cycle of individuals. 

PMID- 25864178
TI  - Analysis of olfactory sensitivity in rainbow trout (Oncorhynchus mykiss) reveals
      their ability to detect lactic acid, pyruvic acid and four B vitamins.
AB  - Salmonid fishes like the rainbow trout Oncorhynchus mykiss have a highly
      developed olfactory sense that allows them to perceive some odorants at very low
      concentrations, such as certain amino acids and bile salts. Previous behavioral
      and electrophysiological studies in salmonids have shown strong responses to
      human skin odor. Because this stimulus represents a complex and heterogeneous
      mixture of components, we sought to determine which odorants contribute to the
      sensitive detection of human skin odor by salmonids. In vivo electroolfactogram
      recordings in O. mykiss revealed lactic acid, pyruvic acid and two B vitamins,
      thiamine and riboflavin, as novel, potent odorants which triggered responses at
      nanomolar concentrations. Two more B vitamins, nicotinic and pantothenic acid,
      were detected at micromolar concentrations. These compounds share important roles
      in cellular energy metabolism, supporting an original role in food search and
      feeding behavior of this species and most likely other fishes. The olfactory
      detection of B vitamins by salmonids represents a new paradigm in chemosensation,
      warranting further investigation in other teleosts. 

PMID- 25864179
TI  - Factors Influencing the Spatial Variation of Microplastics on High-Tidal Coastal
      Beaches in Korea.
AB  - The presence and distribution characteristics of microplastics become a big issue
      due to the adverse effects on marine organisms caused by not only microplastics
      but any incorporated and/or adsorbed pollutants. Distribution of microplastics
      (50- to 5000-MUm size) was determined for three sandy beaches on an isolated
      island in a high-tidal costal region to elucidate spatial distributions in
      relation to beach locations. The abundances of microplastics (n = 21) measured
      were 56-285,673 (46,334 +/- 71,291) particles/m(2) corresponding to the highest
      level globally. Out of observed polymer types, expanded polystyrene was
      overwhelmingly dominant. Although lying toward the estuary of the largest river
      in the country, the north-side beach contained a 100-fold lower abundance than
      two south-side beaches that faced southerly wind and currents that were prevalent
      throughout the study season. In addition, distinct differences between the
      beaches on either side were also present in terms of size distribution and
      spatial homogeneity of microplastics on the same beach. Winds and currents are
      therefore considered to be the driving forces in the distribution of
      microplastics. 

PMID- 25864180
TI  - The Frequency Component of Water Quality Criterion Compliance Assessment Should
      be Data Driven.
AB  - A numerical water quality criterion in the U.S. consists of three components
      representing magnitude, duration, and frequency. While magnitude and duration are
      well defined and conceptually unambiguous, the meaning of the frequency component
      is often debatable. We interpret the frequency component as a tool for accounting
      for uncertainty in estimating the mean concentration of a water quality
      constituent, after revisiting early works on environmental standards and
      criteria. Based on this interpretation, we illustrate management-related issues
      when using the default frequency of one exceedance in 3 years in compliance
      assessment. We propose a data-driven approach for estimating an appropriate
      frequency to ensure a consistent level of confidence in a water's compliance of a
      water quality criterion. The data-driven frequency is determined by water quality
      constituent concentration distribution characteristics and sample size. The
      method is illustrated using two examples.

PMID- 25864181
TI  - (Chemo)radiotherapy after laser microsurgery and selective neck dissection for
      pN2 head and neck cancer.
AB  - This study analyzed the efficacy of transoral laser microsurgery and
      postoperative (chemo) radiotherapy (CRT) for head and neck squamous cell
      carcinoma. Between 1987 and 2007, 318 patients with pN2 neck disease were
      included. Seventy-three patients received laser resection and neck dissection
      alone, 154 postoperative radiotherapy, and 91 postoperative (C)RT. Mean follow-up
      was 58.2 +/- 51.2 months, and locoregional control was significantly better after
      postoperative (C)RT (surgery alone: 42 %, radiotherapy: 57 %, CRT: 59 %; p <
      0.01). Postoperative (C)RT did not have a significant impact on disease-specific
      survival (DSS) (surgery alone: 55 %, radiotherapy alone: 60 %, CRT: 64 %; p =
      0.36). Fifty-seven patients (17.92 %) developed distant metastases, and 39
      patients (12.26 %) presented with secondary malignancies, with no significant
      differences found between the treatment groups. Postoperative (C)RT significantly
      improved locoregional control, but had no significant effect on DSS because of
      high rates of secondary malignancies and distant metastases. Reduced radicality
      in combination with an effective screening might improve prognosis and quality of
      life of these patients. 

PMID- 25864182
TI  - Comparative analysis of the expression of E-cadherin, beta-catenin, and beta1
      integrin in congenital and acquired cholesteatoma.
AB  - E-cadherin, beta-catenin, and beta1 integrin are important cell adhesion
      molecules to maintain epithelial structure and function. We investigated the
      expression of these cell adhesion molecules in cholesteatomas to understand the
      role of cell-cell and cell-extracellular matrix interaction in cholesteatomas. An
      immunohistochemical investigation was carried out on 35 cholesteatoma tissue
      samples (14 congenital, 21 acquired cholesteatomas) and 10 normal retroauricular
      skin (RAS) tissues which are obtained during middle ear surgery. The expression
      rate was measured to find out differences between retroauricular skin and
      cholesteatoma, as well as between congenital and acquired cholesteatoma. E
      cadherin expression rate was significantly lower in the cholesteatoma (spinous
      layer 88.7 +/- 17.9 %, granular layer 54.6 +/- 22.6 %) than in the RAS (100 %,
      74.4 +/- 7.4 %) and in the acquired (83.3 +/- 19.4 %, 48.1 +/- 22.9 %) than in
      the congenital (96.7 +/- 12.0 %, 64.4 +/- 18.8 %). beta-catenin expression rate
      was significantly lower in the cholesteatoma (spinous layer 84.1 +/- 17.2 %,
      granular layer 28.7 +/- 30.8 %) than in the RAS (100 %, 75.9 +/- 6.1 %) and in
      the acquired (78.1 +/- 17.0 %, 17.1 +/- 22.3 %) than in the congenital (93.2 +/-
      13.5 %, 46.1 +/- 34.2 %). The expression pattern of beta-catenin is similar to
      that of E-cadherin. In beta1 integrin, there was no significant difference of the
      expression rate between RAS and cholesteatoma, as well as between congenital and
      acquired cholesteatoma. In conclusion, the expression of E-cadherin and beta
      catenin is reduced in cholesteatoma, and the reduction is more pronounced in
      acquired cholesteatoma than in congenital cholesteatoma. Acquired cholesteatomas
      showed more aggressive characteristics than congenital cholesteatomas in terms of
      cell-cell adhesion.

PMID- 25864183
TI  - Barbed reposition pharyngoplasty (BRP) for OSAHS: a feasibility, safety, efficacy
      and teachability pilot study. "We are on the giant's shoulders".
AB  - A new palatal procedure for snoring/obstructive sleep apnea (OSA) is described.
      The procedure was named as barbed reposition pharyngoplasty (BRP). The technique
      is described step by step. The new surgical technique was carried out in ten
      adult OSA patients with mean age of 53.4 +/- 12.4 years (average 30-70) with
      confirmed retropalatal obstruction. In this pilot study; we assessed the
      feasibility by calculating the number of cases that failed to be operated and
      converted to other palatal technique during the same surgical setting, safety was
      assessed by evaluating both intra-operative and post-operative complications,
      teachability measured by the learning curve of our team members (the time of
      surgical procedure). In this study, the technique is proved to be feasible in all
      cases. There were no significant intra-operative or post-operative complications.
      Objective clinical improvement was confirmed by polysomnography 6 months post
      operative with significant decrease in mean AHI from 43.65 +/- 26.83 to 13.57 +/-
      15.41 (P = 0.007), daytime sleepiness assessed by Epworth Sleepiness Scale from
      11.6 +/- 4.86 to 4.3 +/- 2 (P < 0.01), ODI from 44.7 +/- 27.3 to 12.9 +/- 16.3 (P
      = 0.004). Operative time decreased over the course of the study with an initial
      steep ascent in technical skill acquisition followed by more gradual improvement,
      and a steady decrease in operative time to as short as 20 min. Our preliminary
      results suggest that BRP technique is feasible, safe and effective in management
      of OSA patients. Moreover, it is easy to learn even for not experienced surgeons,
      less time consuming and with no significant complications.

PMID- 25864184
TI  - Acetone-Butanol-Ethanol (ABE) Fermentation Wastewater Treatment by Oleaginous
      Yeast Trichosporon cutaneum.
AB  - In the present study, acetone-butanol-ethanol (ABE) fermentation wastewater with
      high chemical oxygen demand (COD) value (about 18,000 mg/L) was biologically
      treated by oleaginous yeast Trichosporon cutaneum without any pretreatment.
      During fermentation, most COD degradation was finished within 48 h and finally, a
      maximum COD degradation of 68% was obtained. The highest biomass and lipid
      content was 4.9 g/L and 14.7%, respectively. Various materials including sugars
      (glucose and xylose), organic acids (acetic acid and butyric acid), and alcohol
      compounds (ethanol and butanol) could be utilized as carbon sources by T.
      cutaneum simultaneously; thus, it has a broad carbon source spectrum and is a
      potential microorganism for biological treatment for various wastewaters.
      Overall, the lipid composition of microbial oils produced by this bioconversion
      is similar to that of vegetable oils, and thus, it could be used for biodiesel
      production.

PMID- 25864185
TI  - Obesity and Clinical Riskiness Relationship: Therapeutic Management by Dietary
      Antioxidant Supplementation--a Review.
AB  - Obesity is a global health problem affecting all age groups, leading to many
      complications such as type 2 diabetes, systemic hypertension, cardiovascular
      disease, dyslipidemia, atherosclerosis, and stroke. Physiologically, obesity
      arises from metabolic changes in the tissues and organs of the human body; these
      changes result in an imbalance between energy intake and energy expenditure,
      which in turn results in increased fat accumulation in adipose tissue. Such fat
      accumulation predisposes individuals to development of several health problems.
      Two different obesity treatment drugs are currently on the market; Orlistat,
      which reduces intestinal fat absorption via inhibiting pancreatic lipase, and
      Sibutramine, an anorectic or appetite suppressant. Both drugs have hazardous side
      effects, including increased blood pressure, dry mouth, constipation, headache,
      and insomnia. For this reason, a wide variety of natural materials have been
      explored for their obesity treatment potential. Therefore, the present review
      focuses on the safety and efficacy of some herbal medicines in the management of
      obesity through covering their beneficial effects and mechanism of action. 

PMID- 25864186
TI  - Ambient temperature reduction extends lifespan via activating cellular
      degradation activity in an annual fish (Nothobranchius rachovii).
AB  - Ambient temperature reduction (ATR) can extend the lifespan of organisms, but the
      underlying mechanism is poorly understood. In this study, cellular degradation
      activity was evaluated in the muscle of an annual fish (Nothobranchius rachovii)
      reared under high (30  degrees C), moderate (25  degrees C), and low (20  degrees
      C) ambient temperatures. The results showed the following: (i) the activity of
      the 20S proteasome and the expression of polyubiquitin aggregates increased with
      ATR, whereas 20S proteasome expression did not change; (ii) the expression of
      microtubule-associated protein 1 light chain 3-II (LC3-II) increased with ATR;
      (iii) the expression of lysosome-associated membrane protein type 2a (Lamp 2a)
      increased with ATR, whereas the expression of the 70-kD heat shock cognate
      protein (Hsc 70) decreased with ATR; (iv) lysosome activity increased with ATR,
      whereas the expression of lysosome-associated membrane protein type 1 (Lamp 1)
      did not change with ATR; and (v) the expression of molecular target of rapamycin
      (mTOR) and phosphorylated mTOR (p-mTOR) as well as the p-mTOR/mTOR ratio did not
      change with ATR. These findings indicate that ATR activates cellular degradation
      activity, constituting part of the mechanism underlying the longevity-promoting
      effects of ATR in N. rachovii. 

PMID- 25864187
TI  - Nasal probe and toothpick tool use by a wild female bearded capuchin (Sapajus
      libidinosus).
AB  - We report the first observation of probe tool use by a wild adult female bearded
      capuchin (Sapajus libidniosus), at Serra da Capivara National Park (SCNP),
      Brazil. This individual used several stick tools and one grass stem to probe her
      nostrils, usually triggering a sneeze reaction, and also used stick tools to
      probe her teeth or gum. Both of these behaviours were accompanied by inspection
      and licking of the tool following use. We have termed these self-directed actions
      nasal probe and toothpick, and neither has been previously reported in wild
      capuchins. While stick tool use is common among foraging male capuchins at SCNP,
      the novel and at present idiosyncratic activities performed by the female monkey
      add to the known behavioural repertoire for this species. 

PMID- 25864190
TI  - Cystic echinococcosis in Bulgaria 1996-2013, with emphasis on childhood
      infections.
AB  - The objective of this study was to determine some features of cystic
      echinococcosis among children and adolescents, such as epidemiology, diagnosis,
      organ localization, treatment, and social and environmental factors favoring
      transmission of the disease. The 18-year study period (1996-2013) includes
      officially registered primary cases treated surgically, and/or with drug therapy,
      and/or with the puncture, aspiration, injection, reaspiration technique. Organ
      localization of the cysts and the most common diagnostic procedures were studied
      from the patients' medical records. Groups of diseased and healthy children were
      surveyed to outline some of the environmental and social factors influencing
      morbidity. From 1996 to 2013, the average annual incidence of cystic
      echinococcosis in the country was 6.7 per 100,000, but with significant
      variations in the incidence between different age groups. The hydatid cysts in
      children aged 0 to 9 years may most frequently be found in the lungs, in contrast
      to patients from other age groups. Almost 90% of the affected children had
      sustained contact with dogs. At present, among the countries of the European
      Union, Bulgaria holds the highest incidence and prevalence of cystic
      echinococcosis. Childhood echinococcosis remains a serious health problem for the
      country. Therefore, the study of cystic echinococcosis in children has important
      epidemiological significance concerning the intensity of transmission.

PMID- 25864188
TI  - Prophylactic and therapeutic treatment of graft-versus-host disease in Japan.
AB  - Allogeneic hematopoietic stem cell transplantation in Japan is very different
      from that in Western countries in terms of the homogeneous genetic background,
      the preference for bone marrow to peripheral blood stem cells, use of a single
      unit in cord blood transplantation, and frequent use of non-myeloablative
      preconditioning due to a large number of elderly patients. Therefore, conclusions
      obtained from well-designed prospective and/or comparative studies of treatment
      of graft-versus-host disease (GVHD) performed in the United States or Europe may
      not fit Japanese transplant patients. This article reviews the studies of
      prophylactic and therapeutic treatment of acute and chronic GVHD that have been
      conducted in Japan. A randomized study demonstrated a lower incidence of acute
      GVHD in tacrolimus-based prophylaxis than in cyclosporine A-based prophylaxis.
      Retrospective and non-randomized prospective studies suggest that cyclosporine A
      based and tacrolimus-based GVHD prophylaxis regimens are well researched and
      nearly optimized for Japanese patients, including infusion methods and target
      blood concentration. However, most other studies were performed in a single
      institute including a small number of patients, resulting in biased conclusions.
      There is no conclusive report on steroid-refractory acute and chronic GVHD. This
      review provides a baseline for starting prospective studies to create new
      evidence for GVHD treatment from Japan. 

PMID- 25864189
TI  - State-of-the-art acute and chronic GVHD treatment.
AB  - Graft-versus-host disease (GVHD) remains as the major obstacle for successful
      hematopoietic stem cell transplant (HSCT). Roughly half of the patients
      undergoing HSCT develop GVHD which requires treatment, and above 10 % of the
      patient may die because of it. However, GVHD presents with anti-tumor activity,
      called graft-versus-tumor (GVT) effect, and it carries significant anti-tumor
      activity, thus suppressing GVHD completely may increase the relapse of original
      disease. Thus, it is important to control GVHD to the appropriate level. 

PMID- 25864191
TI  - Impacts of enterotoxin gene cluster-encoded superantigens on local and systemic
      experimental Staphylococcus aureus infections.
AB  - Staphylococcus aureus is both a component of the normal skin flora and an
      important pathogen. It expresses a range of recognized and putative virulence
      factors, such as enterotoxins with superantigenic properties. Several
      superantigen genes, i.e., seg, sei, selm, seln, and selo, are encoded by the
      enterotoxin gene cluster (egc), which is found in the majority of S. aureus
      isolates. Carriage of egc is associated with fitness of S. aureus in the gut
      microbiota, but it is not known if it contributes to pathogenicity. We
      constructed egc+ (functional for the seg, selm, and selo genes) and isogenic egc-
      S. aureus mutants, and investigated their virulence profiles in murine infection
      models. No effect of egc was seen in a local skin and soft tissue infection
      model, but in an invasive infection model, increased weight loss was observed
      after infection with the egc+ as compared to the egc- mutant. Mortality and
      arthritis were not affected by egc status. Our data suggest that egc has limited
      effects on the virulence of S. aureus. It may primarily function as a
      colonization factor increasing commensal fitness, although it might have some
      aggravating effects on the infection when the bacteria reach the blood. 

PMID- 25864192
TI  - Statins can increase the risk of herpes zoster infection in Asia.
AB  - This study evaluated whether statin therapy increases the risk of herpes zoster
      (HZ) infection in Asia. This retrospective cohort study used the Longitudinal
      Health Insurance Database (LHID2000). From the LHID2000, patients aged 20 years
      were divided into two cohorts according to their statin use and were matched at a
      1:1 ratio according to propensity scores, which were calculated using a logistic
      regression for estimating the probability of treatment assignment. The primary
      outcome was HZ infection. All patients were followed from the index date until
      the date of HZ infection, withdrawal from the insurance system, or the end of
      2011. The study included 53,069 patients receiving statin therapy as a statin
      cohort and 53,069 patients without statin therapy as a nonstatin cohort. The mean
      follow-up durations for the statin cohort and nonstatin cohort were 4.89
      [standard deviation (SD) = 2.86] years and 4.75 (SD = 2.90) years, respectively.
      The patients in the statin cohort had a 21 % higher risk of contracting HZ
      infection than the patients in the nonstatin cohort [95 % confidence interval
      (CI) = 1.13-1.29]. The incidence of HZ infection increased with the Charlson
      comorbidity index (CCI) score in both cohorts. A high mean defined daily dose of
      the six types of statins considered in this study was associated with a
      significantly increased risk of HZ infection. Statin therapy can increase HZ
      infection in Asia. More benefit-risk evaluations for statin use are necessary in
      Asia. 

PMID- 25864193
TI  - New promising beta-lactamase inhibitors for clinical use.
AB  - Clavulanate, sulbactam, and tazobactam have been used extensively for the last 30
      years, together with beta-lactam antibiotics, to inhibit the effect of beta
      lactamases. Although they have been useful as beta-lactamase inhibitors in many
      cases, their effectiveness is restricted to class A beta-lactamases. With the
      increasing frequency and breadth of beta-lactamases now threatening public health
      throughout the world, we need a much broader spectrum of beta-lactamase
      inhibitors efficient against all classes of beta-lactamases. There are several
      beta-lactamase inhibitors under development, but only a few of them are able to
      inhibit class D and even fewer class B metallo-beta-lactamases (MbetaLs). The
      latter represent a real threat to the latest generations of beta-lactam
      antibiotics, including cephalosporins and carbapenems. Only two beta-lactamase
      inhibitors are, so far, under clinical evaluation, i.e., avibactam and MK-7655.
      The others are years from being clinically available. Although this has caused
      cautious optimism, the progress in this field is far too slow. This is
      particularly so because none of the substances provided are active against
      MbetaLs and because new beta-lactamases invariably force their way into our
      therapeutic armamentarium. While waiting for new antibiotics and new beta
      lactamase inhibitors to become available, it is important to carry out accurate
      clinical and microbiological diagnosis, perform adequate hygiene, and use
      antibiotics properly. This may save lives and reduce resistance resulting from
      inappropriate antibiotic treatment. 

PMID- 25864194
TI  - Pharmacokinetics, Pharmacodynamics, and Tolerability of Single and Multiple Doses
      of Trandolapril, an Effective Angiotensin-Converting Enzyme Inhibitor, in Healthy
      Chinese Subjects.
AB  - Trandolapril is the pro-drug of trandolaprilat, a non-sulfhydryl angiotensin
      converting enzyme inhibitor. This study was designed to assess the
      pharmacokinetics (PK), pharmacodynamics (PD), and tolerability of single and
      multiple doses of trandolapril in healthy Chinese subjects. Healthy subjects (six
      men and six women) were randomized into a single-dose, 3 * 3 crossover study (1-2
      4 mg, 2-4-1 mg, and 4-1-2 mg), and a multiple-dose study (2 mg/day, 6 days).
      Serial blood and urine samples were collected after drug administration and
      analyzed using a validated LC-MS/MS method, and the trandolapril and
      trandolaprilat PK parameters were obtained. PD was evaluated by the changes in
      blood pressure and heart rates after dosing. Tolerability was assessed by
      monitoring adverse events, vital signs, ECGs, and changes in laboratory tests. In
      the single-dose study, trandolapril was absorbed rapidly, and peak plasma levels
      (C max, 1.57, 3.77, and 7.99 ng/mL) and AUCs (1.89, 3.46, and 6.47 ng/mL) were
      dose-dependent. The AUC0-infinity of trandolaprilat was dose-dependent, but in a
      non-linear fashion. The cumulative urine excretion of trandolapril and
      trandolaprilat was 5.51, 6.20, and 7.41 % for three doses, respectively. In the
      multiple-dose study, steady-state pharmacokinetics was observed; there was no
      trandolapril accumulation, but there was mild trandolaprilat accumulation (R =
      1.67). Trandolapril was well tolerated. The most pronounced reductions in blood
      pressure were observed at 8 h after administration, which was later than T max.
      No orthostatic hypotension occurred. The pharmacokinetics and pharmacodynamics
      following single and multiple oral doses trandolapril in healthy Chinese subjects
      are similar to those observed in non-Chinese healthy subjects. 

PMID- 25864195
TI  - Sex differences in orbitofrontal connectivity in male and female veterans with
      TBI.
AB  - More female soldiers are now serving in combat theaters than at any other time.
      However, little is known about possible sex differences underlying the
      neuropathology and manifestation of one of modern war's signature injuries,
      traumatic brain injury (TBI). The paucity of information regarding sex
      differences in TBI is particularly evident when examining changes in executive
      function and emotion regulation associated with post concussive events. The
      current study objective was to observe whether patterns of orbitofrontal (OFC)
      functional connectivity would differ between female veterans with TBI and their
      male counterparts. The study further sought to determine whether OFC connectivity
      might be differentially associated with clinical measures of aggression and
      hostility. Seventeen female veterans and 24 male veterans, age 18 to 25, who met
      criteria for TBI completed resting state magnetic resonance imaging (MRI) and
      clinical assessment measures. Imaging data were analyzed using left and right
      seed regions of the OFC, and regression analyses were conducted to observe the
      relationship between resting state connectivity and self-reported aggression.
      Females and males in this study differed in OFC connectivity, with females
      demonstrating greater connectivity between left and right OFC and parietal and
      occipital regions and males demonstrating greater connectivity between left and
      right OFC and frontal and temporal regions. Significant associations between
      resting state connectivity and clinical measures were found only in male
      veterans. These findings suggest that TBI may interact with sex-specific patterns
      of brain connectivity in male and female veterans and exert divergent effects on
      clinical profiles of aggression post-injury. 

PMID- 25864196
TI  - A pilot fMRI study of the effect of stressful factors on the onset of depression
      in female patients.
AB  - The goal of this study was to observe the differences in brain activation under
      negative emotional picture stimuli in drug-naive female patients with a first
      major depressive episode, comparing patients with and without stressful life
      experiences prior to the onset of depression. Using a 3.0 T magnetic resonance
      imaging (MRI) system, 18 patients who experienced stressful life events (SLEs)
      and 15 patients who did not experience SLEs were scanned under a task-fMRI
      paradigm designed to distinguish between negative and neutral neural responses to
      visual stimuli. SPM 8.0 software was used to process the fMRI data; the
      significantly activated brain regions were recorded and organized in the Montreal
      Neurological Institute (MNI) standard space. Upon stimulation with negative
      emotional pictures, depressed patients who had experienced SLEs showed
      significantly increased activation of the bilateral superior temporal gyrus, left
      middle temporal gyrus, left middle occipital gyrus, left medial frontal gyrus,
      right inferior frontal gyrus, bilateral precentral gyrus, bilateral postcentral
      gyrus, bilateral middle frontal gyrus, right precuneus, left paracentral lobule,
      bilateral thalamus, bilateral hippocampus, and left cerebellum when compared with
      depressed patients who did not experience SLEs.The brain regions that showed
      increased activation in depressed patients who experienced SLEs were primarily
      located in the neural circuits of the emotion processing system; this result
      likely indicates that these patients may have an increased negative cognitive
      bias in the perception, experience, and memory of negative emotional events, as
      well as their response to those events.

PMID- 25864197
TI  - Regional age differences in gray matter diffusivity among healthy older adults.
AB  - Aging is associated with microstructural changes in brain tissue that can be
      visualized using diffusion tensor imaging (DTI). While previous studies have
      established age-related changes in white matter (WM) diffusion using DTI, the
      impact of age on gray matter (GM) diffusion remains unclear. The present study
      utilized DTI metrics of mean diffusivity (MD) to identify age differences in
      GM/WM microstructure in a sample of healthy older adults (N = 60). A secondary
      aim was to determine the functional significance of whole-brain GM/WM MD on
      global cognitive function using the Repeatable Battery for the Assessment of
      Neuropsychological Status (RBANS). Participants were divided into three age
      brackets (ages 50-59, 60-69, and 70+) to examine differences in MD and cognition
      by decade. MD was examined bilaterally in the frontal, temporal, parietal, and
      occipital lobes for the primary analyses and an aggregate measure of whole-brain
      MD was used to test relationships with cognition. Significantly higher MD was
      observed in bilateral GM of the temporal and parietal lobes, and in right
      hemisphere WM of the frontal and temporal lobes of older individuals. The most
      robust differences in MD were between the 50-59 and 70+ age groups. Higher whole
      brain GM MD was associated with poorer RBANS performance in the 60-69 age group.
      Results suggest that aging has a significant and differential impact on GM/WM
      diffusion in healthy older adults, which may explain a modest degree of cognitive
      variability at specific time points during older adulthood.

PMID- 25864198
TI  - WNT1-induced Secreted Protein-1 (WISP1), a Novel Regulator of Bone Turnover and
      Wnt Signaling.
AB  - WISP1/CCN4 (hereafter referred to as WISP1), a member of the CCN family, is found
      in mineralized tissues and is produced by osteoblasts and their precursors. In
      this study, Wisp1-deficient (Wisp1(-/-)) mice were generated. Using dual-energy x
      ray absorptiometry, we showed that by 3 months, the total bone mineral density of
      Wisp1(-/-) mice was significantly lower than that of WT mice. Further
      investigation by micro-computed tomography showed that female Wisp1(-/-) mice had
      decreased trabecular bone volume/total volume and that both male and female
      Wisp1(-/-) mice had decreased cortical bone thickness accompanied by diminished
      biomechanical strength. The molecular basis for decreased bone mass in Wisp1(-/-)
      mice arises from reduced bone formation likely caused by osteogenic progenitors
      that differentiate poorly compared with WT cells. Osteoclast precursors from
      Wisp1(-/-) mice developed more tartrate-resistant acid phosphatase-positive cells
      in vitro and in transplants, suggesting that WISP1 is also a negative regulator
      of osteoclast differentiation. When bone turnover (formation and resorption) was
      induced by ovariectomy, Wisp1(-/-) mice had lower bone mineral density compared
      WT mice, confirming the potential for multiple roles for WISP1 in controlling
      bone homeostasis. Wisp1(-/-) bone marrow stromal cells had reduced expression of
      beta-catenin and its target genes, potentially caused by WISP1 inhibition of SOST
      binding to LRP6. Taken together, our data suggest that the decreased bone mass
      found in Wisp1(-/-) mice could potentially be caused by an insufficiency in the
      osteodifferentiation capacity of bone marrow stromal cells arising from
      diminished Wnt signaling, ultimately leading to altered bone turnover and weaker
      biomechanically compromised bones. 

PMID- 25864201
TI  - Going beyond "trial-and-error" in psychiatric treatments: OPTiMiSE-ing the
      treatment of first episode of schizophrenia.

PMID- 25864200
TI  - Can genomics help usher schizophrenia into the age of RDoC and DSM-6?

PMID- 25864199
TI  - Isoform-selective Genetic Inhibition of Constitutive Cytosolic Hsp70 Activity
      Promotes Client Tau Degradation Using an Altered Co-chaperone Complement.
AB  - The constitutively expressed heat shock protein 70 kDa (Hsc70) is a major
      chaperone protein responsible for maintaining proteostasis, yet how its structure
      translates into functional decisions regarding client fate is still unclear. We
      previously showed that Hsc70 preserved aberrant Tau, but it remained unknown if
      selective inhibition of the activity of this Hsp70 isoform could facilitate Tau
      clearance. Using single point mutations in the nucleotide binding domain, we
      assessed the effect of several mutations on the functions of human Hsc70.
      Biochemical characterization revealed that one mutation abolished both Hsc70
      ATPase and refolding activities. This variant resembled the ADP-bound conformer
      at all times yet remained able to interact with cofactors, nucleotides, and
      substrates appropriately, resembling a dominant negative Hsc70 (DN-Hsc70). We
      then assessed the effects of this DN-Hsc70 on its client Tau. DN-Hsc70 potently
      facilitated Tau clearance via the proteasome in cells and brain tissue, in
      contrast to wild type Hsc70 that stabilized Tau. Thus, DN-Hsc70 mimics the action
      of small molecule pan Hsp70 inhibitors with regard to Tau metabolism. This shift
      in Hsc70 function by a single point mutation was the result of a change in the
      chaperome associated with Hsc70 such that DN-Hsc70 associated more with Hsp90 and
      DnaJ proteins, whereas wild type Hsc70 was more associated with other Hsp70
      isoforms. Thus, isoform-selective targeting of Hsc70 could be a viable
      therapeutic strategy for tauopathies and possibly lead to new insights in
      chaperone complex biology. 

PMID- 25864206
TI  - Reproductive sciences on the forefront of endometriosis news.

PMID- 25864208
TI  - Obesity as a cause of hepatocellular carcinoma.
AB  - During recent years the incidence of obesity has increased significantly, and in
      some instances rapidly, in many resource-rich countries. Paralleling this
      increase has been an increase in the incidence of hepatocellular carcinoma. It
      has been estimated that as many as 90% of obese adults will develop the metabolic
      syndrome. The worldwide incidence of this syndrome in adults at this time ranges
      from 9 to 34%. Furthermore, obesity in childhood increases the risk of obesity in
      adulthood, and hence the development of the metabolic syndrome and hepatocellular
      carcinoma. Ten to 20% of patients with non-alcoholic fatty liver disease progress
      to non-alcoholic steatohepatitis, and 8.3% of the latter develop cirrhosis. Up to
      50% of these patients with cirrhosis, and a significant proportion of those
      without cirrhosis, progress to hepatocellular carcinoma. Much remains to be
      learnt about the mechanisms by which obesity and the metabolic syndrome cause
      hepatocellular carcinoma, although insulin resistance, increased tissue necrosis
      factor activity, alterations in serum lipids, non-alcoholic fatty liver disease
      and non-alcoholic steatosis play important roles. There is also increasing
      evidence that gut microbiota play a role in the development of the metabolic
      syndrome and hence of hepatocellular carcinoma. 

PMID- 25864209
TI  - Diagnosis of liver nodules within and outside screening programs.
AB  - Evaluation of a liver nodule detected with ultrasound includes the recovery of a
      detailed medical history, a physical exam, appropriate contrast imaging
      examinations and, in selected cases, histopathology. In this setting,
      identification of liver disease accompanying a liver nodule helps distinction
      between benign nodules and metastatic malignant nodules from primary liver
      cancer, as recommended by scientific liver societies. Diagnostic algorithms for a
      liver nodule in patients with liver disease involve contrast CT scan, magnetic
      resonance imaging or contrast enhanced ultrasounds to show the typical neoplastic
      pattern of early arterial hyperenhancement wash-in followed by hypoenhancement in
      the late portal phase wash out. The flow charts developed by western societies
      utilize the discriminant criterion of tumor size i.e. the radiological diagnosis
      being endorsed in a nodule equal or greater than 1 cm whereas eastern societies
      rely on the recognition of a typical vascular pattern of the node, independently
      of size. Differential diagnosis should be obtained to differentiate liver related
      nodules like regenerative macronodules (more than 20% of the cases) and the less
      frequent intrahepatic cholangiocarcinoma (~2% of the cases) from liver disease
      unrelated nodules like hemangioma (~4%), neuroendocrine metastatic nodules (~1%)
      and focal nodular hyperplasia. In patients without liver disease, the most common
      liver nodules in the liver are hemangioma (~1.5%), focal nodular hyperplasia
      (0.03%) and hepatocellular adenoma (up to 0.004% in long term users of oral
      contraceptives). Optimization of management of patients with a liver nodule
      requires establishment of a multidisciplinary clinic. 

PMID- 25864210
TI  - The fatigue impact scale for daily use in patients with hepatitis B virus and
      hepatitis C virus chronic infections.
AB  - INTRODUCTION: Fatigue is an important clinical finding in the hepatitis virus
      chronic infection. However, the absence of scales to measure fatigue, translated
      and validated for Brazilian Portuguese, prevents access to information essential
      in clarifying specific clinical conditions in this population. AIM: The aim of
      this study was to determine the psychometric properties of the fatigue impact
      scale for daily use (D-FIS), in Brazilian Portuguese, for patients with the
      hepatitis C virus (HCV) and hepatitis B virus (HBV) chronic infection. MATERIAL
      AND METHODS: In this cross-sectional study, the authors evaluated the D-FIS in
      101 outpatients, followed at the reference hospital. The Mini International
      Neuropsychiatric Interview Brazilian (MINI PLUS) was used to identify psychiatric
      disorders, and the Short Form Health Survey 36-item (SF-36) to evaluate the self
      reported quality of life. We also examined the impact of fatigue on the quality
      of life of this group of patients. RESULTS: Relevant psychometric D-FIS results
      were: floor effect proved to be 1%; skewness was 0.46; item homogeneity was 0.59
      and SEM (SD = 8.51) was 2.4. The Cronbach's alpha was 0.920 and item total
      correlation yielded coefficients ranging from 0.65 (item 1) to 0.85 (item 3). In
      a linear regression model, fatigue and depression influenced the self-reported
      quality of life. CONCLUSION: This study presents that the fatigue scale for daily
      use in Brazilian Portuguese can be considered a useful tool to verify the
      presence of fatigue in patients with the hepatitis viruses B and C.

PMID- 25864211
TI  - Does hepatitis B virus coinfection have any impact on treatment outcome in
      hepatitis C patients on hemodialysis?
AB  - BACKGROUND: HBV/HCV coinfection is a common finding among hemodialysis patients.
      However, there is scarce information concerning the impact of HBV coinfection on
      the response to treatment of HCV-infected patients on hemodialysis. AIM: We aimed
      to compare the rate of sustained virologic response (SVR) to treatment with
      interferon-alfa (IFN) between hemodialysis patients with HBV/HCV coinfection and
      those with HCV-monoinfection. MATERIAL AND METHODS: HCV-infected patients on
      hemodialysis treated with IFN were included. Patients coinfected by HBV/HCV were
      compared to HCV-monoinfected patients, regarding clinical and biochemical
      features and rates of SVR. RESULTS: One hundred and eleven patients were treated.
      HBV/HCV coinfection was observed in 18/111 patients (16%). Coinfected patients
      were younger (p = 002), had more time on dialysis (p = 0.05) and showed a
      tendency to present a higher prevalence of septal fibrosis (p = 0.06). The
      analysis by intention to treat showed SVR of 56% among coinfected patients and
      18% in HCV-monoinfected patients (p = 0.004). CONCLUSION: In conclusion, end
      stage renal disease patients with HBV/HCV coinfection exhibit higher rate of SVR
      to HCV treatment than HCV-monoinfected patients. It is possible that factors
      related to the host immune response and viral interaction could explain the
      better response observed among coinfected patients.

PMID- 25864212
TI  - HCV antiviral therapy in injection drug users: difficult to treat or easy to
      cure?
AB  - Background and rationale of the study. Hepatitis C infection is very common among
      injection drug users(IDUs). In clinical practice there is reluctance to treat
      IDUs, because considered difficult-to-treat. Aim of this study was to evaluate
      the response to antiviral treatment in IDUs compared to non-IDUs. MAIN RESULTS:
      In this observational retrospective study, 204 non cirrhotic patients(112 IDUs,
      92 non-IDUs) with chronic hepatitis C, treated with PEG-IFN and ribavirin in a
      tertiary centre for IDUs of Southern Italy from 2008 to 2011 were analyzed. Age,
      sex, genotype, steatosis, response to previous therapy, rapid(RVR), early(EVR),
      end-of-treatment(ETR), sustained(SVR) virological response were evaluated. IDUs
      were mainly young and males, with prevalence of genotype 3. A higher SVR rate in
      IDUs group compared to non-IDUs only in PerProtocol(PP) analysis (90% vs. 78,9%
      ;p = 0.04). On the contrary, in IntentionToTreat(ITT) analysis, no significant
      difference was relieved. A higher SVR rate at ITT analyses in naive non-IDUs
      patients was found (76,13% vs. 90%, p = 0.021), but at PP analysis wasn't
      confirmed. Treatment was well tolerated; a higher dropout rate was reported in
      IDUs (24 patients) compared to non-IDUs (2 patients). In order to exclude the
      effect of viral genotypes on SVR a genotype matched statistical analysis was done
      and no difference was found. CONCLUSIONS: IDUs naive patients, due to young age
      and high prevalence of genotype 3, appear good candidates to dual antiviral
      therapy with high SVR rates. Dropout is the main non-response cause among these
      subjects, but through an optimal monitoring program with a multidisciplinary
      setting, their "difficult to treat" characteristics can be overcome.

PMID- 25864213
TI  - Impact of H63D mutations, magnetic resonance and metabolic syndrome among
      outpatient referrals for elevated serum ferritin in the Basque Country.
AB  - BACKGROUND AND AIMS: There are limited data on clinical and phenotypic
      characteristics of outpatients referred for hyperferritinemia (HF). To determine
      the causes of HF in outpatients referred to a secondary hospital. MATERIAL AND
      METHODS: A prospective study of 132 consecutive patients with HF (> 200 MUg/L,
      women; > 300 MUg/L, men) was conducted from January-December 2010. RESULTS: Mean
      age, 54.42 years (SD: 13.47, range: 23-83); body mass index (BMI), 28.80 (SD:
      3.96, 17-39); ferritin (SF), 579.54 ng/mL (SD: 296.575, 206-1668); transferrin
      saturation (TSI), 43.87% (SD: 14.09, 12-95); iron (Fe), 134 MUg/dL (SD: 49.68, 55
      322); overweight: 48.31%, and obese: 40.44% (89%), and most patients were men
      (108/132). Regarding HFE mutations, H63D/H63D genotype and H63D allele
      frequencies were 17.5% (vs. 7.76% in controls); and 36% (31% in controls)
      respectively. While 63.6% consumed no alcohol, 18.1% consumed >= 60 g/day, the
      mean being 20.83 (SD: 33.95, 0-140). Overall, 6/132 (4.5%) patients were positive
      for B or C hepatitis. Mean LIC by MRI was 36.04 (SD: 32.78, 5-210), 53 patients
      having normal concentrations (< 36 MUmol/g), 22 (33%) iron overload (37-80), and
      4 (5%) high iron overload (> 80). Metabolic syndrome (MS) was detected in 44/80
      men (55%) and 10/17 women (59%). In this group, the genotype frequency of the
      H63D/H63D mutation was significantly higher than in controls-21.56% vs. 7.76%- (p
      = 0.011); the H63D allelic frequency was 42.15% in MS group and 31% in controls
      (p = 0.027). CONCLUSION: The H63D/H63D genotype and H63D allele predispose
      individuals to HF and MS. MRI revealed iron overload in 33% of patients.

PMID- 25864214
TI  - Risk factors for early repeat ERCP in liver transplantation patients with
      anastomotic biliary stricture.
AB  - INTRODUCTION: Anastomotic biliary strictures (ABS) are a significant clinical
      problem associated with decreased survival post-liver transplantation (LT).
      Contributing to the morbidity of ABS is the need for early (i.e. emergent or
      unplanned) repeat endoscopic retrograde cholangiopancreatographies (ER-ERCPs).
      Our aim was to determine clinical, operative, and endoscopic predictors of ER
      ERCP in patients with ABS. MATERIAL AND METHODS: Medical records of 559 patients
      who underwent LT at our institution from 2000-2012 were retrospectively reviewed
      for pertinent data. The primary endpoint was need for ER-ERCP. Seventeen
      potential predictors of ER-ERCP were assessed in bivariate analyses, and those
      with p < 0.20 were included in multivariate regression models. RESULTS: Fifty
      four LT patients developed ABS and underwent a total of 200 ERCPs, of which 40
      met criteria for ER-ERCP. Predictors of ER-ERCP in bivariate analyses included
      balloon dilation within 3 months post-LT and donation after cardiac death (both p
      < 0.05). Balloon dilation within 3 months post-LT was also associated with
      shorter ER-ERCP-free survival (p = 0.02). Moreover, a significantly higher
      proportion (67%) of patients who underwent balloon dilation within 3 months post
      LT subsequent experienced >= 1 ER-ERCP (p = 0.03), and those who experienced >= 1
      ER-ERCP had lower stricture resolution rates at the end of endoscopic therapy
      compared to those who did not (79 vs. 97%, p = 0.02). In multivariate analyses,
      balloon dilation within 3 months post-LT was the strongest predictor of ER-ERCP
      (OR 3.8, 95% CI 1.7-8.6, p = 0.001). CONCLUSIONS: Balloon dilation of ABS within
      3 months post-LT is associated with an increased risk of ER-ERCP, which itself is
      associated with lower ABS resolution rates. Prospective studies are needed to
      confirm these findings and their implications for endoscopic management and
      follow-up of post-LT ABS.

PMID- 25864215
TI  - Serum ferritin is a biomarker for liver mortality in the Hemochromatosis and Iron
      Overload Screening Study.
AB  - BACKGROUND: We identified no reports of long-term follow-up of participants in
      hemochromatosis screening programs. We evaluated causes of death and survival in
      non-C282Y homozygous Canadian participants in the primary care-based
      hemochromatosis and iron overload screening (HEIRS) study. MATERIAL AND METHODS:
      Initial screening (IS) included transferrin saturation (TS), serum ferritin (SF),
      HFE genotyping (C282Y, H63D), and health questionnaire responses. By definition,
      participants without C282Y or H63D had HFE wt/wt. We linked 20,306 Canadian
      participants to the Ontario Death Registry for dates and causes of death 9 y
      after IS. We computed Cox proportional hazards to identify factors with increased
      death risks and Kaplan-Meier curves to estimate survival of non-C282Y homozygous
      participants with SF <= 1,000 MUg/L and > 1,000 MUg/dL. RESULTS: There were
      19,052 evaluable participants (IS mean age 49 y; 60% women; 93 C282Y
      homozygotes). There were 988 deaths. Significantly increased hazard ratios for
      all-cause mortality were positively associated with TS, SF, men, and C282Y
      homozygosity, and liver disease, diabetes, and heart failure reports. Non-C282Y
      homozygous participants with SF > 1,000 MUg/L had lower survival than those with
      SF <= 1,000 MUg/L (p < 0.0001). CONCLUSIONS: Nine years after initial screening,
      non-C282Y homozygous participants and SF > 1,000 MUg/L was associated with
      decreased survival.

PMID- 25864216
TI  - Clinical characteristics, predictors, and survival among patients with
      hepatopulmonary syndrome.
AB  - BACKGROUND: Hepatopulmonary syndrome (HPS) is a complication of advanced liver
      disease. The impact of HPS on survival is not clearly understood. MATERIAL AND
      METHODS: A prospective study was carried out at Department of Medicine, King
      Edward Medical University Lahore from June 2011 to May 2012. Patients with
      cirrhosis of liver were evaluated for presence of HPS with arterial blood gas
      analysis and saline bubble echocardiography. All patients were followed for 6
      months for complications and mortality. Cox regression analysis was done to
      evaluate role of HPS on patient survival. RESULTS: 110 patients were included in
      the study. Twenty-nine patients (26%) had HPS. MELD score was significantly
      higher (p < 0.01) in patients with HPS (18.93 +/- 3.51) as compared to that in
      patients without HPS (13.52 +/- 3.3). Twenty two (75.9%) patients of Child class
      C, 5 (17.2%) patients of Child class B and 2 (6.9%) patients of Child class A had
      HPS (P 0.03). The clinical variables associated with presence of HPS were spider
      nevi, digital clubbing, dyspnea, and platypnea. HPS significantly increased
      mortality during six month follow up period (HR: 2.47, 95% CI: 1.10- 5.55). Child
      Pugh and MELD scores were also associated with increased mortality. HPS was no
      longer associated with mortality when adjustment was done for age, gender, Child
      Pugh, and MELD scores (HR: 0.44, 95% CI: 0.14-1.41). Both the Child-Pugh and MELD
      scores remained significantly associated with mortality in the multivariate
      survival analysis. CONCLUSIONS: HPS indicates advanced liver disease. HPS does
      not affect mortality when adjusted for severity of cirrhosis.

PMID- 25864217
TI  - Exercise capacity of cirrhotic patients with hepatopulmonary syndrome.
AB  - INTRODUCTION: Hepatopulmonary syndrome (HPS) is characterized by a clinical triad
      of liver disease and/or portal hypertension, intrapulmonary vascular dilatation
      and abnormal arterial oxygenation. These conditions can worsen muscle strength,
      exercise capacity and functionality in the affected population. OBJECTIVE: The
      objective of this study was to compare exercise capacity, functional condition
      and respiratory muscle strength in cirrhotic patients diagnosed with HPS and
      cirrhotic patients without this diagnosis. MATERIAL AND METHODS: This cross
      sectional study used a convenience sample consisting of 178 patients (92 patients
      with HPS and 86 patients without HPS) with a diagnosis of liver cirrhosis caused
      by either alcohol consumption or the hepatitis C virus (HCV). Peak oxygen
      consumption (VO2 peak) was used to verify exercise capacity, the six-minute walk
      test (6MWT) was used to test functionality, and manovacuometry was used to
      evaluate the strength of the respiratory muscles. The Kolmogorov-Smirnov test and
      Student's t-test were used for the statistical analysis. The data were analyzed
      using SPSS 16.00, and p < 0.05 was considered significant. RESULTS: The group of
      patients with the diagnosis of HPS exhibited a lower VO2 peak (14.2 +/- 2.3 vs.
      17.6 +/- 2.6, p < 0.001), shorter distance walked in the 6MWT (340.8 +/- 50.9 vs.
      416.5 +/- 91.4, p < 0.001), lower maximal inspiratory pressure (-49.1 +/- 9.8 vs.
      -74.2 +/- 13.9, p = 0.001) and lower maximum expiratory pressure (60.1 +/- 12.2
      vs. 76.8 +/- 14.7, p = 0.001). CONCLUSION: The group of cirrhotic patients
      diagnosed with HPS exhibited lower values for VO2 peak, distance walked in the
      6MWT and respiratory muscle strength than the cirrhotic patients not diagnosed
      with HPS.

PMID- 25864218
TI  - Safety and efficacy of angiographic occlusion of duodenal varices as an
      alternative to TIPS: review of 32 cases.
AB  - BACKGROUND/RATIONALE OF STUDY: Analyze safety and efficacy of angiographic
      occlusion-with-sclerotherapy/embolotherapy-without-transjugular-intrahepatic
      portosystemic-shunt (TIPS) for duodenal varices. Although TIPS is considered the
      best intermediate-to-long term therapy after failed endoscopic therapy for
      bleeding varices, the options are not well-defined when TIPS is relatively
      contraindicated, with scant data on alternative therapies due to relative rarity
      of duodenal varices. Prior cases were identified by computerized literature
      search, supplemented by one illustrative case. Favorable clinical outcome after
      angiography defined as no rebleeding during follow-up, without major procedural
      complications. RESULTS: Thirty-two cases of duodenal varices treated by
      angiographic-occlusion-with-sclerotherapy/embolotherapy- without-TIPS were
      analyzed. Patients averaged 59.5 +/- 12.2 years old (female = 59%). Patients
      presented with melena-16, hematemesis & melena-5, large varices-5, growing
      varices-2, ruptured varices-1, and other- 3. Twenty-nine patients had cirrhosis;
      etiologies included: alcoholism-11, hepatitis C-11, primary biliary cirrhosis- 3,
      hepatitis B-2, Budd-Chiari-1, and idiopathic-1. Three patients did not have
      cirrhosis, including hepatic metastases from rectal cancer-1, Wilson's disease-1,
      and chronic liver dysfunction-1. Thirty-one patients underwent
      esophagogastroduodenoscopy before therapeutic angiography, including fifteen
      undergoing endoscopic variceal therapy. Therapeutic angiographic techniques
      included balloon-occluded retrograde-transvenous-obliteration (BRTO) with
      sclerotherapy and/or embolization-21, DBOE (double-balloon-occluded
      embolotherapy)-5, and other-6. Twenty-eight patients (87.5%; 95%-confidence
      interval: 69-100%) had favorable clinical outcomes after therapeutic angiography.
      Three patients were therapeutic failures: rebleeding at 0, 5, or 10 days after
      therapy. One major complication (Enterobacter sepsis) and one minor complication
      occurred. CONCLUSIONS: This work suggests that angiographic-occlusion-with
      sclerotherapy/ embolotherapy-without-TIPS is relatively effective (~90%
      hemostasis-rate), and relatively safe (3% major-complication-rate). This therapy
      may be a useful treatment option for duodenal varices when endoscopic therapy
      fails and TIPS is relatively contraindicated.

PMID- 25864219
TI  - MELD score for prediction of survival after emergent TIPS for acute variceal
      hemorrhage: derivation and validation in a 101-patient cohort.
AB  - BACKGROUND AND RATIONALE FOR THE STUDY: The Model for End Stage Liver Disease
      (MELD) score has not been derived and validated for the emergent transjugular
      intrahepatic portosystemic shunt (TIPS) population. We sought to identify
      predictive factors for survival among emergent TIPS patients, and to substantiate
      MELD for outcomes prognostication in this population. RESULTS: 101 patients with
      acute life threatening variceal hemorrhage underwent emergent TIPS (defined by
      failed endoscopic therapy for active bleeding, acute hemoglobin drop, >= 2-unit
      transfusion requirement, and/or vasopressor need) at between 1998-2013.
      Demographic, clinical, laboratory, and procedure parameters were analyzed for
      correlation with mortality using Cox proportional hazards regression to derive
      the prognostic value of MELD constituents. Area under receiver operator
      characteristic (AUROC) curves was used to assess the capability of MELD
      prediction of mortality. TIPS were created 119 +/- 167 h after initial bleeding
      events. Hemodynamic success was achieved in 90%. Median final portosystemic
      pressure gradient was 8 mmHg. Variceal rebleeding incidence was 21%. The four
      original MELD components showed significant correlation with mortality on
      multivariate Cox regression: baseline bilirubin (regression coefficient 0.366),
      creatinine (0.621), international normalized ratio (1.111), and liver disease
      etiology (0.808), validating the MELD system for emergent cases. No other
      significant predictive parameters were identified. MELD was an excellent
      predictor of 90-day mortality in the emergent TIPS population (AUROC = 0.842, 95%
      CI 0.755-0.928). CONCLUSIONS: Based on independent derivation of prognostic
      constituents and confirmation of predictive accuracy, MELD is a valid and
      reliable metric for risk stratification and survival projection after emergent
      TIPS.

PMID- 25864220
TI  - IFNL3 polymorphisms and HCV infection in patients with beta thalassemia.
AB  - BACKGROUND AND RATIONALE FOR THE STUDY: Genome-wide association studies have
      identified host genetic variation to be critical for spontaneous clearance and
      treatment response in patients infected with hepatitis C virus. Recently, the
      role of the IFNL3 polymorphisms in influencing the spontaneous clearance of HCV,
      the response to interferon and the progression of liver fibrosis, was also
      demonstrated in patients with thalassemia major infected by genotype 1b. In the
      present study we retrospectively analyzed 368 anti-HCV positive patients with
      beta-thalassemia at two Italian major centers in Cagliari and Torino. RESULTS:
      C/C variant of polymorphism rs12979860 was related to response to interferon
      treatment and, above all, to spontaneous clearance of the virus. However, the
      positive predictive power was stronger for viral persistence than spontaneous
      clearance and in such respect the TT allele was more predictive than CC. The
      methylation associated polymorphism rs4803221 had independent effects with
      respect to rs12979860 and the haplotype tagged by SNP rs12979860 and rs4803221
      significantly could improve the viral clearance prediction in infected patients.
      Neither necroinflammation or bilirubin values in the chronic phase of the
      hepatitis C were related to IFNL3 polymorphisms. No relation among IFNL3
      polymorphisms and fibrosis stage directly shown by the liver biopsy was found.
      CONCLUSIONS: Also in thalassemia the SNPs on chromosome 19q13 closely associates
      with spontaneous and treatment-induced HCV clearance. The viral clearance
      prediction is significantly improved by the haplotype tagged by SNP rs12979860
      and rs4803221. Neither necroinflammation, bilirubin values or fibrosis stage seem
      to be related to IFNL3 polymorphisms.

PMID- 25864221
TI  - Mycophenolic acid induces apoptosis of hepatic stellate cells in an in vitro
      model of HCV.
AB  - INTRODUCTION: Hepatitis C virus (HCV) infection is an important risk factor for
      the development of liver fibrosis and progression to cirrhosis. Liver
      transplantation as terminal treatment option for liver disease requires life-long
      immunosuppression. However, immunomodulatory therapy may promote reinfection and
      renewed fibrogenesis. Immunosupressive agents may also affect the life cycle of
      hepatic stellate cells (HSC), the main source of extracellular matrix. We thus
      aimed to characterize the effects of three common immunosuppressive agents on HSC
      apoptosis with or without engulfment of HCV infected apoptotic bodies. MATERIAL
      AND METHODS: LX2 cells were incubated with three different immunosuppressants
      (rapamycine, mycophenolic acid or cyclosporine A) and co-incubated for 24 and 48
      h with apoptotic bodies (AB), produced from Huh7 cells or from Con1 cells (Huh7
      cells containing a subgenomic HCV replicon). The engulfment of AB was confirmed
      by immunofluorescence staining. HSC viability, apoptosis rate and expression of
      profibrogenic and proapoptotic genes were quantified. RESULTS: In LX2 cells that
      engulfed Con1 AB, the treatment with mycophenolic acid induced HSC apoptosis and
      reduced collagen 1alpha 1 expression compared to cylosporine A or rapamycine
      treatment. In conclusion mycophenolic acid is a potent inducer of HSC apoptosis
      and attenuates HSC activation and consecutively fibrogenesis in HCV infection.
      Translational studies will need to confirm these mono-culture results in vivo.

PMID- 25864222
TI  - The ability of 17 beta-estradiol to attenuate intrahepatic vasoconstriction to
      endothelin-1 in female rats is lost in cirrhosis.
AB  - BACKGROUND AND RATIONALE: The control of Endothelin-1 (ET-1)-mediated
      intrahepatic vasoconstriction in cirrhosis is beneficial for the alleviation of
      relevant complications. Cirrhosis is accompanied by hypogonadism and altered sex
      hormone status. Besides, sex hormones have vasoactive effects, but it is unknown
      if they influence vascular function in cirrhosis. This study aimed to investigate
      the roles of sex hormones in hepatic vascular reactions to ET-1 in cirrhosis.
      Liver cirrhosis was induced in Spraque-Dawley male and female rats with common
      bile duct ligation (BDL). Sham-operated (Sham) rats were controls. On the 43rd
      day after operations, intrahepatic vascular concentration-response curves to ET-1
      were obtained with the following preincubatioins: 1) vehicle; 2) 17beta
      estradiol; 3) progesterone; 4) testosterone. Livers from sham and BDL rats were
      dissected for real-time polymerase chain reaction analysis of estrogen,
      progesterone and testosterone receptors. RESULTS: Compared with sham males
      perfused with vehicle, sham females presented higher perfusion pressure changes
      to ET-1 which was reversed only by 17 beta-estradiol. In cirrhosis, compared with
      males, 17 beta-estradiol no longer attenuated vascular responsiveness to ET-1 in
      females. In females, BDL rats had lower hepatic estrogen receptor
      alpha(ERbetaalpha) mRNA expression than that in sham rats. CONCLUSIONS: The sham
      females showed a stronger intrahepatic vascular constrictive effect to ET-1 than
      sham males, which could be reversed by 17beta-estradiol. However, the influence
      of 17 beta-estradiol was lost in cirrhotic females, which may be attributed, at
      least partly, to intrahepatic ER alpha down-regulation in females with cirrhosis.

PMID- 25864223
TI  - Black hairy tongue during interferon therapy for hepatitis C.

PMID- 25864224
TI  - Cutaneous amyloidosis associated with autoimmune hepatitis-primary biliary
      cirrhosis overlap syndrome.
AB  - Cutaneous amyloidosis is a rare disease characterized by the deposition of
      amyloid in the dermis. It can be primary or secondary, depending on associated
      diseases. It has been linked to various autoimmune diseases, including primary
      biliary cirrhosis. We present the case of a patient with an autoimmune hepatitis
      primary biliary cirrhosis overlap syndrome with concomitant cutaneous
      amyloidosis, a very unusual association, and discuss similar cases and possible
      pathophysiological implications. 

PMID- 25864225
TI  - Telaprevir may induce adverse cutaneous reactions by a T cell immune-mediated
      mechanism.
AB  - The HCV protease inhibitor telaprevir associated with peginterferon-alpha and
      ribavirin, was widely used in the recent past as standard treatment in HCV
      genotype-1 infected patients. Telaprevir improves the sustained virology response
      rates, but at the same time increases the frequency of adverse cutaneous
      reactions. However, mechanisms through which telaprevir induces cutaneous lesions
      are not yet defined. A 50-year-old woman, affected by HCV genotype 1b, was
      admitted to our Department for a telaprevir-related severe cutaneous eruptions,
      eight weeks after starting a triple therapy (telaprevir associated with
      Peginterferon-alpha and ribavirin). Mechanisms of cutaneous reactions were
      investigated by skin tests with non-irritating concentrations of telaprevir and
      by activating in vitro T lymphocyte with different concentrations. Immediate and
      delayed responses to skin testing were negative, but the drug-induced lymphocytes
      activation was significantly higher as compared to patient's baseline values and
      to parallel results obtained in three healthy subjects (p < 0.05). In conclusion,
      adverse cutaneous reactions of our patient were caused by a telaprevir-induced T
      cell dependent immune mechanism. 

PMID- 25864226
TI  - Papillary in situ and intramucosal adenocarcinoma of the lower third of common
      bile duct. A report and review of the literature.
AB  - We report the case of a 37-year-old woman with no relevant medical history. She
      was admitted to the hospital for epigastric pain related with food intake for 4
      days; the pain did not improve with symptomatic management. A laparoscopic
      cholecystectomy due to acute lithiasic cholecystitis was performed. However,
      after 4 days, postoperative painless jaundice was evident; thus, endoscopic
      retrograde cholangiopancreatography was performed, which revealed an amputation
      of intrapancreatic common bile duct, as well as secondary intra- and extrahepatic
      bile duct dilatation. Brushing of the distal portion of the common bile duct
      revealed a well-differentiated adenocarcinoma. Therefore, a Whipple procedure
      with pylorus preservation was performed. Pathologic diagnosis of a papillary in
      situ adenocarcinoma with two microscopic foci of microinvasion was established.
      The pathologic Tumor-Node-Metastasis (TNM) stage was pT1, pN0, pM0, R0. The
      patient is asymptomatic and disease-free 24 months after surgery. In general,
      adenocarcinomas of the extrahepatic bile ducts are uncommon and have a poor
      prognosis. However, symptomatic patients with early disease stages are even rarer
      and can be cured surgically. 

PMID- 25864227
TI  - Obeticholic acid: expanding the therapeutic landscape of NASH.

PMID- 25864228
TI  - In Memoriam Paul Angulo.

PMID- 25864229
TI  - Mutants of Schizosaccharomyces pombe which sporulate in the haploid state.
AB  - Suppressor mutants of mei1-102, a mutation in one of the mating type cassette
      genes (mat2-P) which blocks the progression into meiosis, were isolated and
      characterized in Schizosaccharomyces pombe. These suppressor mutations conferred
      either temperature-sensitivity or cold-sensitivity. The growth of these strains
      is halted and sporulation initiated at the restrictive temperatures, regardless
      of other conditions usually required for the initiation of meiosis i.e. they
      sporulate in the presence of a nitrogen source and mating type homozygosity.
      Their most striking feature is that they can sporulate from the haploid state.
      The haploidy of these mutants was confirmed by genetical analysis and by
      measurement of the DNA content of the cells. The mutants are all recessive and
      define a single gene pat1. The pat1 gene maps very close to the centromere of
      chromosome II. A meiosis defective mutation in mei5 can suppress the temperature
      sensitivity caused by pat1, indicating some interaction between them. Spores
      produced from a haploid cell have poor viability and appear to contain only 1/2C
      DNA on average.

PMID- 25864230
TI  - Perspective.

PMID- 25864231
TI  - A new offering from the Borden Institute History Series.

PMID- 25864232
TI  - Progress towards measles  elimination, Philippines,  1998-2014.

PMID- 25864233
TI  - Retraction note to: "Human leptin triggers proliferation of A549 cells via
      blocking endoplasmic reticulum stress-related apoptosis" [Biochemistry (Moscow),
      78, No. 12, 1333-1341 (2013)].

PMID- 25864234
TI  - In situ bacterial accumulation on dental restorative materials. CLSM/COMSTAT
      analysis.
AB  - PURPOSE: To evaluate the influence of different restorative materials on the
      biofilm structure accumulated in situ. METHODS: 15 discs of each material
      (ceramic; resin composite; resin-modified and conventional glass-ionomers;
      amalgam) were adapted to palatal devices in order to accumulate biofilm in situ,
      under a cariogenic challenge (20% sucrose solution, 10x/day). After 7 days, the
      specimens were carefully removed and visualized by confocal laser scanning
      microscopy (CLSM). The images were analyzed qualitatively (descriptive analysis
      about cell viability and architecture) and quantitatively using COMSTAT software
      (area, bio-volume, mean thickness, maximum thickness and roughness coefficient of
      the biofilm). The statistical analysis was performed by using the Kolmogorov
      Smirnov and Kruskal-Wallis tests (P <= 5%). RESULTS: The medians of the biofilm
      parameters analyzed showed no statistical difference regarding different
      materials. However, qualitatively, glass-ionomer cements and amalgam showed
      visually a prevalence of non-viable cells forming small clusters distributed by
      the biofilm, and voids were presented in smaller proportion in the biofilm volume
      compared to composite and ceramic.

PMID- 25864235
TI  - Cytokine levels in plasma and gingival crevicular fluid in chronic periodontitis.
AB  - PURPOSE: To evaluate the Th1/Th2/Th17 cytokine levels in plasma and gingival
      crevicular fluid (GCF) from chronic periodontitis patients and healthy controls.
      METHODS: The concentration of interleukin-2 (IL-2), IL-4, IL-6, IL-10, IL-17,
      TNF, and IFN-gamma were determined using a flow cytometric multiplex immunoassay
      (CBA), and was compared between the periodontitis group and the healthy group.
      Spearman rho coefficient was used to correlate cytokines in GCF in the
      periodontitis group and the healthy group, respectively. RESULTS: Comparisons of
      two groups of Th1/Th2/Th17 cytokine levels in plasma and GCF showed no
      statistically significant differences (P > 0.05), except Th17 (IL-17) level in
      plasma that was higher in the periodontitis group than the healthy group (P <
      0.05). A stronger correlation between IL-17/IL-4 and IL-17/IL-10 was observed in
      periodontitis patients than in healthy controls.

PMID- 25864236
TI  - Formation of subsurface dentin lesions using a polymicrobial biofilm model.
AB  - PURPOSE: To simulate an oral demineralization environment by multiple species of
      bacteria by inducing subsurface dentin lesions with a polymicrobial biofilm
      model. METHODS: Polymicrobial biofilms consisting of multiple species of bacteria
      were generated from stimulated saliva using a high-throughput active attachment
      model. Biofilms were grown on dentin specimens in McBain medium containing 0, 0.2
      or 2.5 ppm F and on glass without fluoride for 192 hours. The medium was
      refreshed twice daily, after 10 and 14 hours, until 72 hours, followed by
      treatment for 5 minutes with 400 ppm fluoride. Specimens were recovered after 192
      hours. The number of colony forming units (CFU) was measured, and integrated
      mineral loss (IML) was determined by transversal microradiography. RESULTS:
      Mineral profiles in specimens grown with 0.2F and 2.5F revealed surface layers
      and initial lesions distinct from those grown with 0F. IML was significantly
      lower with 0.2F and 2.5F than with 0F (P < 0.05), although CFUs were similar.
      CFUs of biofilms grown on dentin in medium containing 0F were 10-fold higher than
      on glass (P < 0.05). Subsurface lesions on dentin formed consistently, with their
      growth progression inhibited by application of fluoride. To our knowledge, this
      is the first report describing the induction of subsurface dentin lesions by a
      polymicrobial biofilm model, and this model may be useful for studies of
      demineralization supporting in situ and in vivo models.

PMID- 25864237
TI  - In vitro effect of calcium-containing prescription-strength fluoride toothpastes
      on bovine enamel erosion under hyposalivation-simulating conditions.
AB  - PURPOSE: To evaluate the ability of calcium-containing prescription-strength
      fluoride (F) toothpastes in preventing enamel erosion under low salivary flow
      simulating conditions. METHODS: Enamel and dentin bovine specimens were assigned
      to the following groups: A - placebo; B - 1,100 ppm F/NaF (Aquafresh Advanced); C
      - 5,000 ppm F/NaF (Prevident 5000 Booster); D - 5000 ppm F/NaF+calcium sodium
      phosphosilicate (Topex Renew); and E - 5,000 ppm F/NaF+tri-calcium phosphate
      (Clinpro 5000). Specimens were positioned in custom-made devices, creating a
      sealed chamber on the surface, connected to peristaltic pumps. Citric acid was
      injected into the chamber for 2 minutes, followed by artificial saliva (0.05
      ml/minute), for 60 minutes, 4x/day, for 3 days. Aquafresh was also tested under
      normal salivary flow (0.5 ml/minute), as reference (Group F). Specimens were
      exposed to the toothpastes for 2 minutes, 2x/day. After cycling, surface loss
      (SL) and concentration of loosely- and firmly-bound F were determined. Data were
      analyzed by ANOVA. Results: Group A (placebo) presented highest surface loss
      (SL), while Group F had the lowest, for both substrates. For enamel, none of the
      dentifrices differed from Group B or among each other. For dentin, none of the
      dentifrices differed from Group B, but Group E showed greater protection than
      Group C. Group E presented the highest F concentrations for both substrates, only
      matched by Group D for firmly-bound fluoride on enamel. All fluoridated
      dentifrices tested reduced SL, with no additional benefit from higher F
      concentrations. Some formulations, especially Clinpro 5000, increased F
      availability on the dental substrates, but no further erosion protection was
      observed.

PMID- 25864238
TI  - In vivo evaluation of fluoride dentifrice and diet control on the
      demineralization/remineralization process using laser readouts at the margin of
      the orthodontic bracket/enamel interface.
AB  - PURPOSE: To evaluate, in vivo, the effect of fluoride dentifrice and diet control
      on the demineralization/remineralization processes at the margin of
      bracket/enamel interface bonded with four different bonding materials, using
      optical microscopy and fluorescent laser (DIAGNOdent). METHODS: Premolars in 35
      subjects (11 to 20 years old) were divided into Group 1 (n = 15) and Group 2 (n =
      20). Four bracket/enamel interfaces (near points) and four points at a distance
      of 2 mm (distant points) were observed. Evaluations were made at the following
      times: 15 days before bracket bonding (T0), on day of bonding (T1), 1 week after
      bonding (T2), and 4 weeks after bonding (T3). Subjects received fluoride
      dentifrice, and toothbrush and were instructed to brush 3x/day, after main meals.
      Group 1 received the instructions at T1 and Group 2 at T0 and these were
      reinforced weekly. The Microarch brackets were bonded with four materials:
      Transbond XT; Concise Ortodontico; Fuji Ortho LC and Monolok2. DIAGNOdent laser
      readouts were used for comparison. RESULTS: Data were statistically analyzed by
      Mann-Whitney, Wilcoxon and Friedman tests (P < 0.05). Higher readouts were found
      at nearer points than at distant points; Group 2 presented lower readouts than
      Group 1; No differences were observed among bonding materials.

PMID- 25864239
TI  - Chlorhexidine does not improve but preserves bond strength to eroded dentin.
AB  - PURPOSE: To evaluate the effect of aqueous solutions of chlorhexidine digluconate
      (CHX) in different concentrations on bond strength to eroded dentin up to 6
      months, using normal dentin as a control. METHODS: Exposed flat dentin of
      extracted third molars was only ground with 600-grit SiC paper/1 minute (normal
      dentin - N), or subsequently eroded by a regular-cola soft-drink (eroded dentin -
      E). N and E were acid-etched, washed, dried and rehydrated with 1.5 MUL,
      respectively, of distillated water (control - NC / EC); of 0.004% CHX (N0.004% /
      E0.004%); or of 2% CHX (N2% / E2%). Adper Single Bond 2 was applied in all
      specimens and resin composite buildups were constructed with Filtek Z350.
      Specimens were sectioned in beams, which were tested (MUTBS) immediately or after
      6 months of aging. RESULTS: Microtensile bond strength to eroded dentin was
      always significantly lower than that to normal dentin. Application of tested CHX
      solutions did not exert a significant effect immediately; however, after aging,
      the 2% CHX prevented abrupt bond strength loss both to eroded and normal dentin.

PMID- 25864240
TI  - Evaluation of nanohydroxyapatite-containing toothpaste for occluding dentin
      tubules.
AB  - PURPOSE: To compare dentin tubule occlusion by dentifrices containing either
      nanohydroxyapatite (10%nHAP and 15%nHAP), sodium monofluorophosphate (Na-MFP) or
      NovaMin (NovaMin). METHODS: All 80 participants wore four intraoral appliances
      bearing dentin blocks while using one of the four test dentifrices (n =
      20/dentifrice) twice daily for 14 days. The four appliances were removed in pairs
      after 7 and 14 days. One treated block from each of the test periods (7 and 14
      days) and their untreated controls were examined with SEM to determine the level
      of tubule occlusion. The remaining two treated blocks and their controls were
      used to determine tubule permeability to dye solution. Effectiveness was compared
      statistically (ANOVA/Tukey's) based on % area covered by deposited precipitate
      layer (%DPL), % dye penetration inhibition (%DPI) and percentage of fully-open
      (%FOT), partially-occluded (%POT) and completely-occluded (%COT) tubules in each
      block calculated relative to the number of tubules in their control blocks.
      RESULTS: SEM showed increased %COT and %DPL overtime. After 7 and 14 days, %COT,
      %POT, %DPL and %DPI were significantly lower with Na-MFP when compared to 10%nHAP
      (P < 0.01), NovaMin (P < 0.05) and 15%nHAP (P < 0.001), the three of which were
      not significantly different from each other in those four variables. A reverse
      trend was observed with %FOT (P < 0.001). Within the same dentifrice, no
      difference in %COT, %POT, %FOT, %DPI and %DPL after 7 and 14 days, except with Na
      MFP in which %DPL significantly (P< 0.05) increased with usage. In conclusion,
      nanohydroxyapatite-containing and NovaMin-containing toothpastes showed equal and
      more effectiveness in occluding dentin tubules than Na-MFP toothpaste.

PMID- 25864241
TI  - Difference in effectiveness between strontium acetate and arginine-based
      toothpastes to relieve dentin hypersensitivity. A systematic review.
AB  - PURPOSE: To present an overview of clinical evidence of strontium acetate and
      arginine-based toothpastes, in order to determine which of these substances was
      the most effective to relieve dentin hypersensitivity (DH). METHODS: An
      electronic search was performed in PubMed, EMBASE, The Cochrane Library, LILACS,
      Web of Science and Open Grey databases. The search strategy included MeSH terms,
      synonyms and keywords with no language or date restriction. Randomized controlled
      clinical trial studies that compared the effectiveness of arginine/calcium
      carbonate and strontium acetate toothpaste were included. The risk of bias in the
      included studies was assessed and classified through the Cochrane Collaboration's
      common scheme for bias. Data were subgrouped and heterogeneity was tested via
      comprehensive meta-analysis. RESULTS: A total of 3,883 potentially relevant
      studies were identified. After title and abstract examination, only six studies
      fulfilled the eligibility criteria and were classified as having a "low risk of
      bias". The majority of studies found better results for arginine/calcium
      carbonate in comparison with strontium acetate in alleviating DH. Only one study
      reported superior efficacy of strontium acetate, and only for tactile stimuli,
      after 8 weeks of home use. The arginine/calcium carbonate-based toothpaste
      provided a higher level of efficacy in terms of DH relief than the strontium
      based toothpaste.

PMID- 25864242
TI  - Efficacy of a combined in-office/home-use desensitizing system containing 8%
      arginine and calcium carbonate in reducing dentin hypersensitivity: an 8-week
      randomized clinical study.
AB  - PURPOSE: To determine the efficacy in reducing dentin hypersensitivity (DHS) of a
      combined in-office and home-use desensitizing system, each product containing 8%
      arginine and calcium carbonate (Test), following a dental scaling procedure,
      compared to the combination of a conventional prophylactic paste and a potassium
      nitrate dentifrice (Control), in a group of patients with known dentin
      hypersensitivity. METHODS: An 8-week clinical study, with 50 subjects, was
      conducted in Piracicaba, Sao Paulo, Brazil, using a double-blind/two treatment
      design. Air blast sensitivity assessments were used to compare the efficacy of
      the two approaches using both the Schiff scale as well as a Visual Analogue Scale
      (VAS). RESULTS: Immediately after prophylaxis, the Test treatment provided
      significant reduction in DHS when compared to baseline values (VAS = 26.2% and
      Schiff = 29.1%), while for Control treatment this difference was not
      statistically significant (VAS = 8.1% and Schiff = 6.6%). The comparison between
      groups after prophylaxis showed a greater DHS reduction for the Test treatment (P
      < 0.05). The reductions in DHS after 2, 4 and 8 weeks were significant for both
      groups, however, when considering Schiff scale, the Test treatment provided
      greater DHS reduction after 2 weeks (44.5% for Test versus 27.7% for Control) and
      4 weeks (55.2% for Test and 40.5% for Control), while after 8 weeks there was no
      significant difference between groups (71.1% for Test versus 61.1% for Control).

PMID- 25864243
TI  - An in vitro evaluation of the effect of fluoride products on white spot lesion
      remineralization.
AB  - PURPOSE: To compare the effect of combinations of fluoride (F) products on
      remineralization of caries-like lesions. METHODS: Demineralized human enamel
      specimens were assessed by surface microhardness (SMH), stratified and allocated
      to five treatments groups: (1) Toothpaste containing 1% nano hydroxyapatite (HAP)
      + 1,450 ppm F; (2) Tooth mousse containing 10% casein phosphopeptide-amorphous
      calcium phosphate (CPP-ACP) + 900 ppm F plus F toothpaste (1,450 ppm F as NaF);
      (3) F varnish containing 22,600 ppm F plus F toothpaste (1,450 ppm F as NaF); (4)
      F toothpaste (1,450 ppm F as NaF); and (5) placebo--distilled water (P). Each
      group was treated in a 21-day pH-cycling model. Groups 1, 4 and 5 were treated
      2x/day. In Group 3, the tooth mousse was administered 1x/day plus 2x/day F
      toothpaste treatment. In Group 4, F varnish was administered 1x/week plus 2x/day
      treatment with F toothpaste. After cycling, SMH was re-measured and cross
      sectional microhardness measurements were taken. RESULTS: Groups 1-4 produced
      significant rehardening of enamel. In the superficial layer (25-50 MUm deep)
      significantly higher mineralization (up to 83%, by Volume (V), P < 0.0001) was
      achieved for Groups 2 and 3. In the area of 75-100 MUm deep, the highest
      mineralization was observed for Groups 1 and 4 (V% = 68-83%).

PMID- 25864244
TI  - Antimicrobial effects of carbamide peroxide against a polymicrobial biofilm
      model.
AB  - PURPOSE: To investigate the in vitro antimicrobial effects of carbamide peroxide
      (CP) and CP-based home bleaching agents against polymicrobial (PM) biofilms.
      METHODS: Using a high-throughput active attachment model, PM biofilms were
      cultured on glass coverslips by diluting the stimulated saliva of one healthy
      adult. All experiments were performed anaerobically in McBain medium, which was
      refreshed twice daily. After biofilm formation for 24 or 72 hours, the biofilms
      were treated with 0.5%, 2.5%, 5%, or 10% CP, 20-fold dilutions of HiLite Shade Up
      (HS) or Opalescence Regular (OR), 0.2% chlorhexidine digluconate (CHX), 0.2% NaF,
      or deionized water (n = 10 each). Biofilms were dispersed and the number of
      colony forming units (CFU) was measured on tryptic soy agar blood plates.
      Coverslips containing 72-hour biofilms treated with 0.5% and 10% CP and deionized
      water were stained and scanned by confocal laser scanning microscopy (CLSM).
      RESULTS: Treatment of 24- and 72-hour biofilms with HS, OR and CH yielded
      significantly fewer colonies than treatment with water or 0.2% NaF. No growing
      colonies were observed after treatment with 10% CP. CLSM showed that the
      percentage of dead bacteria increased as the concentration of CP increased.

PMID- 25864245
TI  - Joining the diaspora of deaf memoirists: a personal account of writing deafness.
AB  - In this essay, the author describes how, and why, she tackled a lifetime of
      questions about her deafness and experiences of being deaf by writing a memoir
      called The Art of Being Deaf. While researching her memoir, the author discovered
      that the questions about her deafness that she most needed to answer were her
      own. Having first read many memoirs by other deaf writers and novels with deaf
      characters, the author set about composing her own narrative of deafness in a
      fresh way. She not only came to an improved understanding of her deaf self, but
      grew into a more authentic understanding of her whole self, reconciling her
      memories of the deaf girl she once was with the adult deaf woman she is now. The
      author illustrates how the act of writing a memoir can be an important tool in
      resolving questions of identity.

PMID- 25864246
TI  - Levonorgestrel-releasing intrauterine device used for dysmenorrhea: five-year
      literature review.
AB  - Intrauterine devices (IUDs) provide highly effective, long-term, safe, reversible
      contraception, and are the most widely used reversible contraceptive method
      worldwide. The levonorgestrel-releasing IUD (LNG-IUD), originally designed for
      long-term contraceptives, is now recognized to provide non-contraceptive health
      benefits. These include severe dysmenorrhea and/or heavy menstrual bleeding
      associated with uterine myoma, endometriosis, and adenomyosis. This report aims
      to review the last five-year literature on the efficacy and safety of the LNG-IUD
      in women with dysmenorrhea. Dysmenorrhea has been reported to decrease in all
      women. LNG-IUD seems to be superior over copper-releasing IUD for improving
      dysmenorrhea. The LNG-IUD is beneficial for symptom recurrence and endometriotic
      cyst recurrence after conservative surgery for patients with severe pain related
      to endometriosis. There is also evidence to support its role in menstrual
      problems of severely obese adolescent females. Expulsion, one of the important
      factors for IUD acceptability, is rare but more common in women with distorted
      uterine cavity. In the treatment of dysmenorrhea, the LNG-IUD is equal or
      superior to treat with systemic progestins or oral contraceptives even in
      adolescent or menopausal women.

PMID- 25864247
TI  - Association of sympathetic nervous system activity with polycystic ovarian
      syndrome.
AB  - Polycystic ovary syndrome (PCOS) is a disease with high prevalence which has
      various clinical manifestations and increased risk of long-term complications,
      such as dyslipidemia, diabetes, metabolic syndrome, and hormone related tumor.
      However, the etiology of PCOS is still unclear. Consequently, the effect of
      symptomatic treatment is not always satisfactory and the prognosis is also
      unpredictable. Currently, commonly psychological syndromes and imbalance of
      sympathetic neuroendocrine system have been found in PCOS population, and
      increasing evidence highlighted the hypothesis that characteristics of PCOS could
      be partially explained by the instability of the sympathetic nervous system
      (SNS). Furthermore, surgical intervention of animal trials in order to normalize
      SNS could improve symptoms of PCOS. This review attempted to clarify the
      relationship between SNS and PCOS development and then discuss the possible new
      therapies in PCOS treatment via regulating the SNS.

PMID- 25864248
TI  - Prolonged saltatory fetal heart rate pattern leading to newborn metabolic
      acidosis.
AB  - PURPOSE: The saltatory pattern, characterized by wide and rapid oscillations of
      the fetal heart rate (FHR), remains a controversial entity. The authors sought to
      evaluate whether it could be associated with an adverse fetal outcome. MATERIAL
      AND METHODS: The authors report a case series of four saltatory patterns
      occurring in the last 30 minutes before birth in association with cord artery
      metabolic acidosis, obtained from three large databases of internally acquired
      FHR tracings. The distinctive characteristics of this pattern were evaluated with
      the aid of a computer system. RESULTS: All cases were recorded in uneventful
      pregnancies, with normal birthweight singletons, born vaginally at term. The
      saltatory pattern lasted between 23 and 44 minutes, exhibited a mean oscillatory
      amplitude of 45.9 to 80.0 beats per minute (bpm) and a frequency between four and
      eight cycles per minute. CONCLUSIONS: A saltatory pattern exceeding 20 minutes
      can be associated with the occurrence of fetal metabolic acidosis.

PMID- 25864249
TI  - Neonatal mortality rate and risk factors in northeast China: analysis of 5,277
      neonates in 2005.
AB  - BACKGROUND: Healthcare has dramatically improved for both mothers and neonates
      over the last three decades in China. However, the reported rates of morbidity
      and mortality vary among different regions of China, and the exact rates in
      Northeast China are unknown. This study aimed to determine neonatal morbidity and
      mortality rates and the associated risk factors in Northeast China. MATERIALS AND
      METHODS: Neonates born in 2005 at seven hospitals in five major cities of
      Heilongjiang province in Northeast China were recruited. Standardized
      questionnaires on both the mother and neonate were conducted by trained
      investigators. The questions included demographic data on the mother, the
      mother's weight, gestational age (GA), complications during pregnancy, method of
      delivery, neonate's gender, weight, general health situation, and complications
      after delivery. Results: A total of 5,277 neonates were included, with a male to
      female ratio of 1.07. The incidence ofpreterm delivery was 8.7%, which was
      associated with an increased age of the mother, a history of preeclampsia
      eclampsia, premature rupture of membranes, and intrauterine distress. Morbidity
      occurred in 7.0% of neonates, including hypoxic ischemic encephalopathy (2.4%),
      asphyxia (1.6%), pneumonia (1.6%), hyperbilirubinemia (0.5%), intracranial
      hemorrhage (0.5%), meconium as- piration syndrome (0.2%), and ingestion syndrome
      (0.2%). The overall mortality was 9.5%0. Preterm delivery, maternal history
      ofpreeclamp- sia-eclampsia, hypoxic ischemic encephalopathy, intracranial
      hemorrhage, pneumonia, asphyxia, and meconium aspiration syndrome were
      independent risk factors for mortality with odds ratios (95% confidence interval)
      of 17.42 (7.31-38.9), 12.52 (Table 3) (3.91-16.82), 10.13 (2.52-19.86), 9.77
      (2.35-19.93), 4.15 (1.78-9.52), 2.18 (1.21-5.47), and 2.76 (2.11-6.32),
      respectively (all P<0.01). CONCLUSIONS: In 2005, the overall morbidity and
      mortality was 7.0% and 9.5%0, respectively in northeast China, and preterm
      delivery was the highest risk factor for neonatal mortality. The prevention on
      preterm delivery should be a top priority for the improvement of neonatal
      healthcare.

PMID- 25864250
TI  - Normal "high" thyroid stimulating hormone (TSH) levels and pregnancy rates in
      patients undergoing IVF with donor eggs.
AB  - OBJECTIVE: To determine if a relationship exists between pregnancy rates obtained
      in patients undergoing in vitro fertilization (lVF) with donor eggs and levels of
      thyroid stimulating hormone greater than 2.5 mlU/L but still within a range
      considered normal. STUDY DESIGN: Retrospective comparative cohort study. With
      prior approval of the Ethics Committee, 233 patients undergoing IVF with donor
      eggs, in a two-year period, were included. Patients were grouped depending on the
      thyroid stimulating hormone (TSH) level. Pregnancy rates were compared.
      Statistical analysis was made with the Chi-square test. RESULTS: Pregnancy rates,
      depending on the TSH level, were 56.6% in patients with TSH levels below 2.49
      mU/L vs. 21.6%, in patients with levels above 2.5 mU/L. This difference was
      statistically significant (p < 0.001). CONCLUSIONS: Mild abnormalities of thyroid
      function may adversely affect the pregnancy rates in patients un- dergoing in
      vitro fertilization with donor eggs. A possible alteration in endometrial
      function may be associated.

PMID- 25864251
TI  - Evaluation of uterine perfusion in postmenopausal women receiving hormone
      replacement therapy.
AB  - OBJECTIVES: The authors evaluated uterine perfusion in postmenopausal women
      receiving hormone replacement therapy (HRT) by using transvaginal Doppler
      ultrasonography. MATERIALS AND METHODS: A total of 60 postmenopausal women
      receiving HRT were included in this prospective case control study. The patients
      were divided into two groups. The study group received HRT for at least one year.
      Uterine perfusion was evaluated by transvaginal Doppler ultrasonography and
      pulsatility index (PI) and resistance index (RI) of uterine arteries were also
      recorded with a 5-7.5 MHz transvaginal probe. All patients gave informed consent
      to the study. Statistical analyses were carried out by using the statistical
      packages for SPSS 15.0 for Windows. RESULTS: Demographic characteristics of the
      cases showed no statistically significant difference between the groups. There
      was a statistically significant difference between PI and RI of uterine arteries.
      In the study group PI and RI were lower than in the control group. As the
      duration of HRT use was prolonged, a decline in PI and RI increased (p < 0.05).
      CONCLUSION: The current study showed that HRT has positive effects on uterine
      blood flow in postmenopausal women and may be evaluated by transvaginal Doppler
      ultrasonography.

PMID- 25864252
TI  - A randomized-clinical trial examining a neoprene abdominal binder in gynecologic
      surgery patients.
AB  - PURPOSE OF INVESTIGATION: Pain control and early ambulation are two important
      postoperative goals. Strategies that decrease morphine use while increasing
      ambulation have the potential to decrease postoperative complications. In this
      study the authors sought to determine the effect of an abdominopelvic binder on
      postoperative morphine use, pain, and ambulation in the first day after surgery.
      MATERIALS AND METHODS: The authors randomly assigned 75 patients undergoing
      abdominal gynecologic surgery to either binder or not after surgery. Demographic
      data and surgical characteristics were collected. Outcome variables included
      morphine use, pain score, time to ambulation, and number of ambulations. RESULTS:
      A group at high risk for decreased mobility was identified and the binder
      increased the number of ambulatory events by 300%, 260%, and 240% in patients
      with vertical incisions, age over 50 years, and complex surgeries, respectively.
      Morphine use and pain scores were not significantly different. CONCLUSION: The
      binder increased ambulations in the subset of patients at the highest risk for
      postoperative complications: elderly, cancer patients, and vertical incisions.
      Routine use of the binder may benefit particularly high-risk gynecologic surgical
      patients.

PMID- 25864254
TI  - Maternal serum pregnancy-associated plasma protein-A levels in hyperemesis
      gravidarum: a prospective case control study.
AB  - PURPOSE: To investigate if maternal serum pregnancy-associated plasma protein-A
      levels are affected in hyperemesis gravidarum (HG). MATERIALS AND METHODS: A
      prospective case control study was conducted in 169 HG cases who had one or more
      antepartum hospitilization for HG. The control pregnancies were 132 and were
      selected randomly among all women who had first trimester prenatal screening in
      antenatal outpatient clinic between 2011 and 2012. RESULTS: Maternal serum
      pregnancy-associated plasma protein-A levels were significantly higher in
      hyperemesis gravidarum group compared with control group (p = 0.002 p < 0.05 95%
      CI). Power analysis of independent sample t-test, two-sided, for pregnancy
      associated plasma protein-A was 0.88. Maternal serum free beta-human chorionic
      gonadotropin values were not different between two groups (p > 0.05). CONCLUSION:
      Increased pregnancy-associated plasma protein-A levels associated with HG, even
      after excluding potential cofounders.

PMID- 25864253
TI  - Craniofacial catch-up growth in intrauterine growth retarded rats following
      postnatal nutritional rehabilitation.
AB  - PURPOSE: The aim of the study was to analyze the effect of postnatal nutritional
      rehabilitation on the craniofacial growth in rats with intrauterine growth
      retardation (IUGR). MATERIALS AND METHODS: Wistar rats were assigned to one of
      the following groups: control, Sham-operated, and IUGR. The IUGR was produced by
      uterine vessels bending (day 14 of pregnancy). At days 1, 21, 42, 63, and 84 of
      postnatal life, each animal was X-rayed, and neural and facial length, width and
      height were measured. Volumetric and morphometric indices were calculated.
      RESULTS: The decreased maternal-fetal blood flow during the last-third of the
      gestation period modified cranial size and shape of both sexes at birth.
      DISCUSSION: Postnatal nutritional rehabilitation is not fully sufficient to
      reverse the prenatal growth retardation. There are specific responses depending
      on the sex and the age of the IUGR pups. Regardless of the changes in size, the
      shape is not modified during all the postnatal period.

PMID- 25864255
TI  - The influence of ritodrine alone or in combination with nifedipine on maternal
      cardiovascular side effects and pregnancy outcomes.
AB  - OBJECTIVE: To compare the influence of ritodrine alone or in combination with
      nifedipine on maternal side effects and suppressing preterm labor. MATERIALS AND
      METHODS: This retrospective study included 213 pregnancies with preterm labor (20
      34 weeks) from May 2002 to April 2010 in Kyungpook National University Hospital
      in Daegu, Korea. Obstetric medical records were reviewed for both maternal
      characteristics and neonatal outcomes, including birth weight, Apgar score,
      admission to neonatal intensive care unit (NICU), ventilator support, and
      neonatal mortality. Maternal side effects such as tachycardia, pulmonary edema,
      and hyperglycemia were also reviewed. RESULTS: Of 213 patients, 109 received
      ritodrine only and 104 were given ritodrine and nifedipine. There was no
      statistical difference between the two groups with regards to pregnancy outcomes
      and neonatal complications. Pregnancy prolongation over seven days was achieved
      more in the combination therapy group, with borderline statistical significance
      (59.6% vs. 72.1%, p = 0.055). Sixty-nine cases experienced maternal side effects;
      four cases were categorized as serious and 65 cases were mild. CONCLUSION: In the
      treatment of preterm labor, the combination regimen of ritodrine and nifedipine
      can be more effective than ritodrine alone for prolonging gestation over seven
      days. Moreover, as the combination did not cause severe maternal side effects, it
      may be considered as a safe and effective method to prolong gestation in patients
      with preterm labor.

PMID- 25864256
TI  - The possible role of zinc in the etiopathogenesis of endometriosis.
AB  - PURPOSE OF INVESTIGATION: Aim of the study was to evaluate the possible
      involvement of zinc in the complex pathogenic process behind the onset and
      perpetuation of endometriotic lesions. To study the level of zinc serum between a
      group of patients affected by endometriosis and a group of healthy patients.
      MATERIALS AND METHODS: The study included 86 women: 42 patients whose
      histodiagnosis had revealed pelvic endometriosis and 44 healthy patients. The
      authors measured the serum zinc concentration for all patients. RESULTS: The
      group of patients with endometriosis presented serum zinc concentration of 1010
      +/- 59.24 microg/l. The observation group presented a serum zinc concentration of
      1294 +/- 62.22 microg/l. CONCLUSION: The results showed that serum zinc levels in
      women with endometriosis are decreased and this seems to actually confirm that
      this microelement can possibly affect the multifactorial pathogenesis of the
      disease. As a matter of fact, zinc interferes with many biological processes,
      among which inflammation and immunity, which seem to be the base of the
      development of the lesions. Therefore, the authors believe that this hypothesis
      requires more attention and further investigation to determine its
      reasonableness. If the results are confirmed, this study opens up future
      prospects as for the treatment of endometriosis, taking into account also the
      role of zinc in the onset of male sterility and the development of testicles.
      Zinc could in fact be used as marker to detect women at high risk of
      endometriosis and for the elaboration of a new treatment for sterility, from
      which these women often suffer.

PMID- 25864257
TI  - Relation of peritoneal fluid and serum vascular endothelial growth factor levels
      to endometriosis stage.
AB  - OBJECTIVE: It is a well known fact that endometriosis is linked with apoptosis,
      extracellular matrix formation, and angiogenesis. In this study, the authors aim
      to investigate the relation between the extent of endometriosis and vascular
      endothelial growth factor (VEGF). MATERIALS AND METHODS: Twenty-one patients who
      received laparoscopic intervention due to endometriosis constituted the patient
      group, whereas 19 patients who were operated due to extra-endometrial benign cyst
      were included in the control group. Following the laparoscopic pelvic assessment,
      peripheral blood samples and two cc of free peritoneal fluid from the Douglas
      pouch were obtained simultaneously. The samples were studied with regards to VEGF
      level via solid phase sandwich enzyme-linked immunosorbent assay (ELISA) method.
      RESULTS: In the patient group, eight cases were diagnosed with Stages I and II
      endometriosis, while 13 cases were diagnosed with Stages III and IV
      endometriosis. Among the Stage I and II cases, serum VEGF levels were
      statistically significantly higher, as compared to the Stage III and IV cases, as
      well as the control group. Discussion: In conclusion, the authors found a
      relationship between elevated serum VEGF levels and early stage endometriosis.

PMID- 25864258
TI  - Study of individualization therapy for 61 patients with cesarean scar pregnancy.
AB  - OBJECTIVE: To investigate the clinical value of the individualization therapy for
      cesarean scar pregnancy (CSP). MATERIALS AND METHODS: According to the individual
      characteristics of the CSP in 61 patients admitted and treated by the People's
      Hospital of Yuyao City, China between March 2010 and February 2013, methotrexate
      (MTX) with leucovorin (CF) or uterine artery chemotherapy embolization (UACE)
      were used to kill the embryos, stanch, and prevent bleeding. Guided by
      hysteroscopy or B ultrasound, uterine curettage was carried out under the
      surveillance of laparoscopy if necessary. RESULTS: Fifty-four cases of patients
      were treated by UACE. MTX with CF was used,in seven cases. Uterine curettage was
      performed in 44 cases under the guidance of hysteroscopy. Six cases were under
      the surveillance of the B ul- trasound and both hysteroscopic guidance and B
      ultrasound surveillance were used in seven cases. The lesions disappeared in two
      cases after transabdominal excision and two cases after UACE. All of the 61
      patients were cured without hysterectomy. CONCLUSION: Selection of
      individualization treatment programs according to the characteristics of the
      disease could improve the efficacy and prognosis of patients with CSP. The
      appropriate timing to perform curettage was five to seven days after embryo
      killing in order to reduce bleeding and shorten the course of the disease.

PMID- 25864259
TI  - Fetal nasal bone length at 11(+0) - 13(+6) weeks of gestation: an evaluation of
      554 consecutive cases.
AB  - PURPOSE OF INVESTIGATION: To develop a nomogram for estimating nasal bone length
      (NBL) at 11(+0) - 13(+6) weeks of gestation in 554 consecutive cases and to
      determine the value of NBL measurement in screening for chromosomal
      abnormalities. MATERIALS AND METHODS: NBL and crown-rump length (CRL) were
      examined in 554 fetuses at 11(+0) - 13(+6) weeks' gestation. A nomogram for NBL
      was developed with data from 479 healthy fetuses in which fetal profile
      examination was possible. Reference values, including percentiles, weie
      calculated for each gestational age. RESULT: A linear correlation was noted
      between CRL and NBL in healthy fetuses at 11(+0) - 11(+6), 12(+0) - 12(+6) and
      13(+0) - 13(+6) weeks of gestation. Mean NBL was 2.18 +/- 0.53 mm, 2.46 +/- 0.45
      mm, and 2.91 +/- 0.55 mm in healthy fetuses, for these time frames, respectively.
      NBL increased significantly with CRL from respective means of 2.26 +/- 0.43, 2.60
      +/- 0.48, 2.77 +/- 0.43, and 3.16 +/- 0.52 mm at 45 - 54.9, 55 - 64.9, 65 +/-
      74.9, and 75 - 84 mm. CONCLUSION: The authors developed a NBL nomogram with data
      from normal, healthy Turkish fetuses at 11(+0) - 13(+6) weeks of gestation. These
      reference ranges may prove useful in prenatal screening and diagnosis of
      syndromes known to be associated with nasal hypoplasia.

PMID- 25864260
TI  - Expression of anti-inflammatory mediator lipoxin A4 and inflammation responsive
      transcriptive factors NF-kappa B in patients with preeclampsia.
AB  - OBJECTIVE: To evaluate the role of lipoxin A4 (LXA4), NF-kappaB p65 in
      preeclampsia. MATERIALS AND METHODS: LXA4 in blood serum and the lipoxin A4
      receptor (ALX-R), NF-kappaB p65 mRNA, protein expressions in placenta-specific
      tissues were obtained from patients with preeclampsia and normal pregnancy.
      RESULTS: Levels of lipoxin A4 in women with mild preeclampsia was significantly
      high (p < 0.05). There was no significant statistical difference between normal
      pregnancy and severe preeclampsia (p > 0.05). The mRNA expression of ALX-R was
      significantly low in women with preeclampsia than in control group (p < 0.01) and
      mRNA expression of NF- kappaB p65 was significantly high in preeclampsia (p <
      0.01). The immunohistochemical staining of NF-kappaB p65 protein was stronger in
      severe preeclampsia group whereas staining of ALX-R in placental tissue was
      weaker than in control group (p < 0.01). ALX-R mRNA was negatively correlated
      with NF-kappaB (p < 0.0001), but there was no correlation between LXA4 and ALX-R
      mRNA. CONCLUSION: There was an excessive maternal inflammatory response in
      preeclampsia. LXA4, ALX-R, and NF-kappaB p65 may be involved in the disease
      process ofpreeclampsia.

PMID- 25864261
TI  - Sexual dysfunction in Turkish women with dyspareunia and its impact on the
      quality of life.
AB  - PURPOSE OF INVESTIGATION: The authors aimed to determine the prevalence of female
      sexual dysfunction (FSD) among Turkish dyspareunic women and to establish the
      associated factors with FSD. Furthermore, they aimed to investigate if
      dyspareunia and possible associated sexual complaints were related to impaired
      quality of life (QoL). MATERIALS AND METHODS: The study included 154 women
      admitted to the present gynecology department at a tertiary center in the west
      region of Turkey, 67 of which suffered from dyspareunia. The remaining 87
      sexually healthy women were included in the control group. FSD was assessed with
      19-item validated female sexual function index (FSFI). QoL was assessed using
      short form 36 (SF-36). The chi-squared test and t-test were used for analysing
      the group differences. Pearson's correlation test was used to determine the
      effect of the variables of FSFI on the SF-36. Multivariance analysis and logistic
      regression was used to determine independent risk factors for FSD and to estimate
      odds ratio (OR) with 95% confidence interval (CI). RESULTS: The incidence of FSD
      in dyspareunic group and control group was 86.57% and 36.8%, respectively (p <
      0.001). Dyspareunic women had lower scores with regards to sexual desire,
      arousal, lubrication, orgasm, satisfaction, and pain domains at significant level
      (p < 0.001). Education level, time period after the last delivery, duration of
      marriage, parity, and dyspareunia were significantly related to FSD. However,
      dyspareunia was an independent risk factor for FSD (OR 11.49; 95% CI 4.95-26.67).
      Regarding the impact on the QoL, dyspareunic women had lower scores with regards
      to the physical role, social function, bodily pain, and vitality domains.
      CONCLUSION: The present results show that dyspareunia has a major impact on
      women's sexual function and QoL. Clinicians have an important role for
      encouraging women to report their sexual complaints. Identifying dyspareunia and
      treating FSD may positively affect women's sexual function and overall QoL.

PMID- 25864262
TI  - Serological prenatal screening and diagnosis for Down syndrome.
AB  - OBJECTIVE: This study aimed to review and summarize the recent first-trimester
      and second-trimester prenatal screening and sequential prenatal screening to
      analyze the role of the existing prenatal screening system in the secondary
      prevention of birth defects. MATERIALS AND METHODS: This study included 3,665
      cases of 14-20-week pregnant women that underwent prenatal screening using double
      serum alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (beta-hCG)
      and ultrasound screening; 512 cases of 9-12-week pregnant women underwent triple
      serological detection of serum beta-hCG, pregnancy-associated plasma protein A
      (PAPP-A), and nuchal translucency (NT) for early screening. RESULTS: The overall
      screening was with a high-risk rate of 8.52%. Among 356 cases of high-risk
      pregnant women, a total of 308 cases underwent karyotype analysis of fetal
      amniotic fluid cells. Of these, five cases of trisomy 21, one case of trisomy 18
      and one case of "47, XXY" were diagnosed; among 37 cases of neural tube defect
      (NTD)-affected high-risk pregnant women, one case of anencephalus, and one case
      of open spina bifida were diagnosed. CONCLUSION: The overall detection rate for
      chromosome abnormalities was about 3.25% in the existing screening system, which
      could effectively prevent these seriously teratogenic fetuses from being born.

PMID- 25864263
TI  - The triad of luteal phase ocular migraines, interstitial cystitis, and
      dyspareunia as a result of sympathetic nervous system hypofunction.
AB  - PURPOSE: To evaluate whether ocular migraines can be related to sympathetic
      nervous system hypofunction, especially when associated with interstitial
      cystitis and dyspareunia. MATERIALS AND METHODS: Dextroamphetamine sulfate was
      administered to a 34-year-old woman with a history of long-term interstitial
      cystitis, dyspareunia, and ocular migraines that were resistant to all other
      therapies. RESULTS: In a short length of time the sympathomimetic amine therapy
      almost completely abrogated all of her symptoms and they have remained controlled
      while she continues on the drug. CONCLUSIONS: This is the first report of
      effectively treating ocular migraines with dextroamphetamine sulfate. The
      gynecologist should not be afraid to initiate therapy without referral to other
      specialists, especially if other symptoms of the sympathetic neural hyperalgesia
      edema syndromes exist, e.g., bladder pain of pelvic origin and dyspareunia.

PMID- 25864264
TI  - Simultaneous heart valve replacement surgery and abdominal subtotal hysterectomy:
      case report.
AB  - A middle-aged woman with rheumatic heart disease, mitral valve prolapse and
      incompletely closed mitral valve medium, patent foramen ovale, merge multiple
      uterine fibroids, and moderate blood loss anemia underwent mitral valve
      replacement surgery with total abdominal hysterectomy under general anesthesia
      and cardiopulmonary bypass condition. The surgery was successful, and
      postoperative bleeding, blood clots, heart failure, and other related
      complications did not occur. Heart valve replacement surgery with the surgical
      treatment of uterine fibroids effectively improves the safety of surgical
      treatment for patients as well as reduces the patient's medical expenses and risk
      of secondary surgery and trauma.

PMID- 25864265
TI  - Matrix array transducer for the examination of fetal heart.
AB  - The X6-1 xmatrix array transducer allows a completely new approach to the
      diagnostic ultrasound: it permits visualization of fetal heart in real time,
      without the need for gating, and it is unaffected by motion artefacts. It is
      obtained in real time, without any spatial reconstruction. The authors compared
      this technology with the traditional one in two case reports: a diagnostic doubt
      of small muscular ventricular septal defect was solved using this new technique;
      a diagnosis of complete atrioventricular septal defect was confirmed. Three
      dimensional real-time imaging would seem very precise in the study of fetal
      heart: the defects were fully visualized from any angulations. This new
      technology is promising but from the authors' limited experience, there is no
      evidence to use it in routine practice. It should be very useful to commence a
      prospective study on fetuses at risk while testing the superiority of this
      technique.

PMID- 25864266
TI  - Heart failure, metabolic acidosis, and postoperative multiple organ failure after
      anesthesia for cesarean section in a patient with Takayasu arteritis: a case
      report.
AB  - The incidence of Takayasu arteritis (TA) is approximately one in 200,000. The
      prevalence of this disease is higher among Asian women under the age of 30. Most
      pregnant women with mild TA receive spinal anesthesia for cesarean sections.
      Despite difficulties in measuring blood pressure, the entire surgical process,
      including the administering of anesthesia, is generally stable. Studies in this
      area are rare. The authors report a case of a pregnant woman with TA who received
      anesthesia for a cesarean section and then suffered for heart failure, metabolic
      acidosis, and postoperative multiple organ failure. The authors hope to
      contribute to the clinical studies on the subject of anesthesia for pregnant
      women with TA.

PMID- 25864267
TI  - Transvaginal repair of rectovaginal fistula by filling with bulbocavernosus fat
      pad and retaining scar tissue.
AB  - The authors performed transvaginal repair of rectovaginal fistual (RVF) with
      bulbocavernosus fat pad by incising left side of the labia majora and retained
      scar tissues which were formed after three months for one patient. Repair of the
      RVF was successful and the patient had normal diet and defecation at a week after
      surgery. Previous gynecological surgery performed on the patient resulted in RVF
      accompanied by weak rectal tissues. Retaining the tissues and scars surrounding
      to the fistula and filling the fistula with bulbocavernosus fat pad tissue
      increased rectal wall thickness and facilitated healing. The efficacy of this
      surgical technique will need further studies with larger patient cohorts to
      establish a clear success rate.

PMID- 25864268
TI  - Uterine preservation in placenta percreta complicated by unscarred uterine
      rupture at second trimester in a patient with repeated molar pregnancies: a case
      report and brief review of the literature.
AB  - Placenta-percreta causing uterine rupture in unscarred uterus is a rare obstetric
      surgical emergency that can cause maternal and perinatal morbidity and mortality.
      A 25-year-old woman presented with abdominal pain for four days. Previously, she
      had undergone two suction curettages for complete hydatiform moles. Ultrasound
      revealed a non-viable fetus with an estimated gestational age of 21 weeks and
      free fluid and coagulum in the abdominal cavity. An emergency laparotomy was
      performed because of the acute abdomen. At exploration, the placenta had invaded
      the entire thickness of the myometrium and the non-viable fetus was in the
      abdominal cavity. The uterus was closed with a double-layer of interrupted
      sutures and uterine-sparing surgery was performed. The patient was discharged on
      postoperative day seven. The authors present a case of placenta-percreta in an
      unscarred uterus complicated with uterine rupture during the second-trimester
      that was managed successfully with uterine repair. They also review the
      literature briefly and discuss similar cases managed conservatively in the second
      trimester.

PMID- 25864269
TI  - Conjoined twins: three cases in one tertiary medical center and literature
      review.
AB  - Conjoined twins are so rare that most obstetricians will not be personally
      exposed to such cases during their professional lifetimes. The authors report
      three cases including one of dicephalic parapagus conjoined twins and two
      thoracopagus conjoined twins in the present tertiary medical center, and discuss
      the diagnosis and management details. They also review the incidence,
      embryological, diagnostic, obstetrical, and prognostic aspects of conjoined
      twins. Regular antenatal visits and serial ultrasound scanning are crucial for
      early diagnosis of conjoined twins, optimal obstetric management and perinatal
      preparation still remain challenging, and multidisciplinary cooperation is
      urgently needed.

PMID- 25864270
TI  - Asymptomatic spontaneous complete uterine rupture in a term pregnancy after
      uterine packing during previous caesarean section: a case report.
AB  - Uterine rupture is a life-threatening obstetrical complication with significant
      neonatal and maternal morbidity. The authors report a 36-year-old woman with a
      history of previous caesarean section because of pre-eclampsia and antepartum
      haemorrhage at 31 gestational weeks during her first pregnancy. Postpartum
      haemorrhage occurred and the uterine cavity was packed with gauze for reducing
      blood loss. After two years, she underwent elective, repeat caesarean section at
      38+1 gestational weeks with no abdominal pain or vaginal bleeding. During the
      operation, a six- to seven-cm-long defect was found in the lower uterine segment,
      with complete separation of the uterine scar and disruption of the visceral
      peritoneum. A live baby was delivered. The postoperative course was uneventful.
      Uterine dehiscence and rupture should be suspected in the presence of risk
      factors such as previous caesarean section, especially uterine packing involved.
      Spontaneous silent rupture can occur in women without any alarming symptoms.

PMID- 25864271
TI  - A case of uterine rupture in mid-trimester spontaneous abortion: a complication
      of gemeprost vaginal administration.
AB  - The only prostaglandin analogue licensed in Italy for induction of labour in
      spontaneous and therapeutic abortion is gemeprost. The authors report a case of
      spontaneous uterine rupture of a scarred uterus, for previous caesarean sections,
      in a woman at 20 weeks of gestation with a diagnosis of spontaneous abortion. She
      received a pessary of gemeprost every three hours. After the fifth pessary, she
      complained of severe pain. At the ultrasound examination, uterine cavity appeared
      empty and the dead fetus was dislocated in the abdomen. Emergency laparotomy was
      performed and uterine tear was repaired. To induce labour for fetal demise or
      therapeutic abortion in second trimester in women with scarred uterus, the
      authors decided to lengthen the time between administrations of pessary from four
      to five hours depending on patient's symptoms. However the appropriate drug
      regimen has still to be found and more data are necessary.

PMID- 25864272
TI  - Irreducible inguinal hernia containing rudimentary uterine horn, ovary, and
      fallopian tube.
AB  - The authors present a typical case of inguinal hernia containing rudimentary
      uterine horn, ovary, and fallopian tube. During the operation of herniorraphy the
      right ovary and fallopian tube with rudimentary uterine horn were found in the
      hernia sac. The woman underwent laparoscopic hysterectomy three months before
      herniorrhaphy and was diagnosed with unicornuate uterus. The authors reviewed the
      case and suggested that detailed examination such as gynecological examination
      and magnetic resonance imaging be performed routinely in those females with
      inguinal hernias.

PMID- 25864273
TI  - The prevalence of primary neck and shoulder pain, and its related factors in
      Japanese postpartum women.
AB  - PURPOSE: This study investigated the prevalence, location, and severity of neck
      and shoulder pain (NSP), its disturbance of quality of life (QOL), and the
      factors related to NSP in Japanese postpartum women. MATERIALS AND METHODS: The
      study involved 308 postpartum women who had a medical examination one month after
      delivery. The questionnaire consisted of the background and details of NSP. Mood
      states were evaluated using the Profile of Mood States-Brief (POMS-B), Japanese
      Version. RESULTS: The prevalence of NSP was 73.1%, one-fourth of which occurred
      after birth. The most common area was the superior part of the trapezium muscles.
      Prevalence was associated with past history of premenstrual syndrome (PMS),
      anemia during pregnancy, time per breastfeeding, and the mean POMS-B Fatigue
      score. Total breastfeeding time a day, the mean POMS-B score for Fatigue,
      Confusion, Anger-Hostility, and Depression were significantly higher for "worse"
      after birth than those for "no-change/relief". The disturbance of daily life due
      to NSP in postpartum women with past history of PMS and Hiesho were significant
      higher than that for women without those. CONCLUSIONS: The prevalence of NSP in
      postpartum women was very high. The factors which affect NSP were the mental
      states, breastfeeding, past history of PMS, and anemia during pregnancy.

PMID- 25864274
TI  - The application of high definition flow imaging in fetal hemodynamics.
AB  - OBJECTIVE: This work aims to investigate the application of high definition flow
      imaging (HD-flow) in fetal hemodynamics, and establish reference range of
      hemodynamic parameters in fetal with different gestational ages. MATERIALS AND
      METHODS: A thousand of normal pregnant women were divided into five groups: 18
      22, 23-27, 28-32, 33-37, and 38-40 gestational weeks. Color Doppler flow imaging
      (CDFI) and HD-flow were adopted to display the heart structure and measure the
      blood flow velocity. The pulmonary vein display results were scored. The results
      of HD-flow and CDFI were compared. RESULTS: The catheter peak velocity of fetal
      mitral, tricuspid, aortic, pulmonary artery, aortic arch, ductal arch, the
      inferior vena cava, pulmonary vein, and venous catheter increased continuously
      with the increase of gestational age, showing a linear correlation. HD-flow was
      superior to CDFI on the display of pulmonary vein in 18-22, 23-27, and 28-32
      weeks (p < 0.05), but was not in 33-37 and 38-40 weeks. HD-flow was an accurate
      positioning method for the pulmonary veins. CONCLUSION: HD-flow can make accurate
      evaluation of fetal hemodynamics and the demonstration of low blood flow, such as
      pulmonary venous, is better than CDFI. Pulmonary veins can be accurately
      positioned with HD-flow. HD-flow can demonstrate the main blood vessels of the
      whole fetal circulation and can display the spatial relationship of the blood
      vessels. It is of important clinical significance in hemodynamic study.

PMID- 25864275
TI  - Leptin increases luteinizing hormone secretion of fasting female rats.
AB  - PURPOSE: To investigate whether leptin acts directly on the anterior hypophysis
      by influencing gonadotropin secretion in vivo. MATERIALS AND METHODS: Cycling
      female rats were catheterised for frequent blood sampling and were either fasted
      or allowed free access to food. Stereotactic lesion of the medial preoptic area
      (MPOA) of the hypothalamus was performed in order to eliminate gonadotropin
      releasing hormone (GnRH) production. Leptin was administered at a dose of one
      mg/kg i.v. and blood samples were taken just before leptin administration and
      then after 30, 60, 90, 120, and 180 minutes. Plasma gonadotropin levels were
      determined. With completion of sampling, the brains were removed and the
      localisation of the lesions was verified histologically. RESULTS: Leptin at one
      mg/kg induced an increase in luteinizing hormone (LH) secretion in fasting rats,
      both in those with a lesion and those with intact medial preoptic area with a
      peak occurring 90 minutes after infusion. The augmenting effect was more
      prominent when the hypothalamus was intact. There was no effect in fed animals
      with or without lesion. Similarly, no effect was observed on follicle stimulating
      hormone (FSH) levels in any of the experimental groups. CONCLUSIONS: Leptin acts
      directly on the hypophysis enhancing LH but not FSH secretion. Nutritional state
      influences leptin's effect on the hypothalamus and the hypophysis.

PMID- 25864276
TI  - Effect of nitric oxide inhalation combined with high-frequency oscillatory
      ventilation on the prognosis of neonatal severe hypoxemia.
AB  - OBJECTIVE: The current study aimed to analyze the short-term and long-term
      curative effects of nitric oxide (NO) inhalation combined with high-frequency
      oscillatory ventilation (HFOV) on neonatal severe hypoxemia. MATERIALS AND
      METHODS: A total of 98 neonates meeting the inclusion criteria were
      retrospectively analyzed. The control group comprised of 48 neonates and the NO
      inhalation group consisted of 50 neonates. In the control group, conventional
      mechanical ventilation was replaced by HFOV. In the experimental group, NO
      inhalation combined with HFOV was performed. The death rates within 28 days,
      mechanical ventilation and oxygen therapy time, and complications in both groups
      were observed. The survivors in both groups were followed up for 18 months for
      neural development evaluation. RESULTS: The treatment group showed a
      significantly lower death rate and noticeably shorter mechanical ventilation and
      oxygen therapy time than the control group (8% vs. 22.9% with t = 4.20 andp <
      0.05; 5.84 +/- 3.36 days vs. 8.05 +/- 5.48 days with t = 2.42 and p < 0.05; and
      8.02 +/- 4.31 days vs. 12.45 +/- 5.14 days with t = 4.63 and p < 0.001). They did
      not show significant differences with regards to the complications and the
      incidences of cerebral palsy, hearing and visual impairments, and severe nervous
      damage (p > 0.05). CONCLUSION: NO inhalation combined with HFOV significantly
      decreases the death rate of neonates with severe hypoxemia and reduces their
      mechanical ventilation and oxygen therapy time. It does not increase early
      adverse effects or affect long-term neurodevelopment.

PMID- 25864277
TI  - Troponin I and D-Dimer levels in preeclampsia and eclampsia: prospective study.
AB  - OBJECTIVE: The aim of this study was to evaluate serum cardiac troponin I and D
      Dimer (D-Di) levels in preeclampsia (PE), eclampsia (E), and normotensive healthy
      pregnant women in third trimester in order to define their diagnostic value.
      MATERIALS AND METHODS: The study group consisted of 42 preeclamptic patients and
      16 eclamptic patient; 108 healthy normotensive pregnant women in third trimester
      who were chosen from outpatients clinic and examined regularly used as a control
      group. Serum cardiac troponin I and D-Di levels were measured using an
      immunoassay. RESULTS: The average levels of troponin I were 0.0134 +/- 0.0091,
      0.017 +/- 0.0085, 0.180 +/- 0.136 in control group, preeclamptic, and eclamptic
      patients, respectively. The levels of troponin in eclamptic patients were
      statistically higher than the normotensive and preeclamptic group (p = 0.016, p =
      0.014). There were no differences in terms of troponin I level between
      preeclamptic group and normotensive pregnant women in third trimester (p =
      0.089). The average D-Di levels were 634 +/- 228 ng/ml, 1426 +/- 430 ng/ml, 2067
      +/- 580 ng/ml in control group, preeclamptic, and eclamptic patients,
      respectively. The levels of D-Di in preeclamptic and eclamptic patients were
      found significantly higher than the control groups (p = 0.034, p = 0.020).
      CONCLUSION: Serum troponin I levels increased in eclamptic patient because of
      myocardial damage. An increased level of troponin was not detected in
      preeclamptic patients. However; D-Di level increased in preeclamptic and
      eclamptic patients.

PMID- 25864278
TI  - The effect of maternal polycystic ovary morphology on first-trimester maternal
      serum biochemical markers of aneuploidy and fetal nuchal translucency thickness.
AB  - OBJECTIVE: To evaluate the effect of maternal polycystic ovary (PCO) morphology
      on maternal serum free beta-human chorionic gonadotropin (beta-hCG), pregnancy
      associated plasma protein A (PAPP-A), and nuchal translucency (NT) thickness in
      the first-trimester. MATERIAL AND METHODS: A total of 92 pregnant women in the
      first-trimester were included in the study. Of them, 57 had PCO morphology, and
      35 women constituted the control group, with apparently normal ovaries. Maternal
      serum free beta-hCG, PAPP-A, and NT thickness were measured and compared in all
      patients. RESULTS: The multiples of median (MoM) levels of serum free beta-hCG
      were significantly higher in the PCO morphology group compared to the normal
      ovary group (p = 0.024). However, the MoM levels of PAPP-A were similar in both
      groups (p = 0.947). No difference was found between the groups in terms of
      fasting glucose levels and NT measurements (p = 0.976 and 0.565, respectively).
      CONCLUSION: In pregnancies with maternal PCO morphology, the presence of higher
      maternal serum free beta-hCG levels may require correction in the calculation of
      risks related to first-trimester screening for chromosomal abnormalities. Larger
      studies are needed to confirm our preliminary data.

PMID- 25864279
TI  - Effect of hypertonic sodium chloride hydroxyethyl starch 40 on ET, TXB2, 6-keto
      PGF1alpha, and ANP of preeclampsia in caesarean section.
AB  - OBJECTIVE: Preeclampsia is a unique disease of pregnancy. Delivery via caesarean
      section is the most important way of terminating the pregnancy and treating
      preeclampsia. Perioperative fluid therapy is performed to maintain the
      circulatory volume and reduce tissue edema. This study evaluated the effects of
      hypertonic sodium chloride hydroxyethyl starch 40 (HSH40) as perioperative fluid
      therapy for preeclampsia patients. MATERIALS AND METHODS: Forty preeclamptic
      women were randomly divided into two groups: the Ringer's solution group and the
      HSH40 group. Their ECG, HR, MAP, and SPO2 were monitored. Their MVP and HR were
      recorded at five, eight, and ten minutes after anesthesia induction and at the
      end of the caesarean section. The corresponding volume of infusion, blood loss,
      and urine output during the operation were also recorded. Venous samples were
      collected before HSH40 infusion and 30 min after infusion to measure the plasma
      concentrations of ET, TXB2, 6-keto-PGF1alpha, and ANP via a radioimmunoassay.
      RESULTS: HSH40 infusion significantly decreased the plasma ET levels (p < 0.01),
      significantly changed the plasma ANP and TXB2 levels (p < 0.05), and
      significantly increased the plasma 6-keto-PGF1alpha levels (p < 0.01) in the
      experimental group compared with those before infusion. The plasma levels of ET,
      ANP, TXB2, and 6-keto-PGF1alpha did not significantly change in the control
      group. Compared with T1, MAP decreased significantly at T2, T3, T4, and T5 within
      groups (p < 0.05) and between the two groups. MAP significantly changed at T2,
      T3, T4, and T5 (p < 0.05). HR did not significant change at T1, T2, T3, T4, and
      T5 within or between groups. Volume of infusion and urine volume significantly
      differed between groups (p < 0.05). CONCLUSION: Low-dose HSH40 lowers the plasma
      levels of vasoconstrictor substances (ET and TXB2) and increases the levels of
      vasodilator substances (6-keto-PGF1alpha and ANP) during preeclampsia. It
      effectively maintains and stabilizes the circulating blood volume, increasing
      renal blood flow, which improves renal function and increases urine output.

PMID- 25864280
TI  - A comparison of the molecular distribution of proangiogenic factors in
      endometrium of missed abortions and of voluntary first trimester termination
      cases.
AB  - OBJECTIVE: The authors aimed to evaluate the angiogenic changes that occur in the
      cases with missed abortions compared with the voluntary termination of pregnancy
      as control group, with this controlled clinical study. MATERIALS AND METHODS: The
      study included fifteen healthy volunteer women with unwanted pregnancy less than
      10th gestational week in an academic research environment. The patients were 19
      women between 6th and 11th gestational weeks diagnosed with missed abortion as
      the patient group. Immunohistochemistry was utilized to examine temporal and
      spatial expression of vascular endothelial growth factor (VEGF) and their two
      receptors: VEGF-R1 (Flt-1) and VEGF-R2 (Flk-1/KDR), and Trombospondin-1, eNOS,
      iNOS, and HIF-1alpha in the both deciduas and placenta of the both groups.
      RESULTS: This study discovered the significant difference (p < 0.005) between the
      groups of controlled and missed abortion in the decidual and placental cell
      components, and has put forward that thrombospondin and iNOS have an impact on
      abortion through antiangiogenic effect in cases of missed abortions. CONCLUSIONS:
      The potential role of molecules affecting angiogenesis in the etiology of missed
      abortion has been evaluated and the authors aimed for this to be a guide for
      studies on further treatments and on the prevention of the development of missed
      abortions.

PMID- 25864281
TI  - How does early cognitive behavioural therapy reduce postpartum depression?
AB  - Postpartum depression (PPD) is a frequent mood disorder. Early identification of
      mothers at risk is crucial to successful prevention. Cognitive Behavioural
      Therapy (CBT) is an effective preventing therapy. Objectives of this study are to
      identify mothers at risk for PPD using the Edinburgh Postnatal Depression Scale
      (EPDS) and evaluate the efficacy of CBT for the prevention of PPD in these
      mothers. Women were recruited during their second postpartum day. Two groups were
      selected: mothers with high risk (EPDS score >= 10) and mothers with low risk
      (EPDS score < 10) of PPD. The first group underwent CBT. Follow up was carried
      out at 40 days, three, six, and 12 months after childbirth. APGAR score, neonatal
      hospitalization, delayed breastfeeding, and cesarean section were significant
      obstetric risk factors. Mothers at high risk of PPD presented a statistically
      valid improvement of EPDS score. Mothers with low risk of PPD did not have CBT
      and showed a higher EPDS score than mother at high risk at 12 months. PPD
      prevention is possible through early identification of mothers at risk and early
      cognitive behavioural therapy.

PMID- 25864282
TI  - A different approach to placenta previa accreta: intrauterine gauze compress
      combined B-Lynch uterine compression suture.
AB  - OBJECTIVE: To retrospectively evaluate the effectiveness of intrauterine gauze
      compress combined B-Lynch uterine compression suture in placenta previa accreta
      cases. MATERIALS AND METHODS: Five patients who experienced postpartum hemorrhage
      (PPH) due to placenta previa accreta between January 2009 and March 2013 in the
      present clinics, who were irresponsive to medical therapy, and that had applied
      intrauterine gauze compress combined B-Lynch uterine compression suture were
      analyzed retrospectively. RESULTS: Intrauterine gauze compress combined B-Lynch
      uterine compression sutures were applied in patients in whom medical therapy
      failed. Intrauterine gauze compresses were removed under sedation. No patients
      required hysterectomy or any complications. DISCUSSION: B-Lynch suture in
      combination with intrauterine gauze compress can be applied easily in placenta
      previa accreta cases. This is considered to be a highly successful method.

PMID- 25864283
TI  - The outcome and course of pregnancies complicated with fetal neural tube defects.
AB  - PURPOSE: The objectives of this study were as follows: to present the course and
      outcome of pregnancies complicated with neural tube defects, determine the
      association between prenatal ultrasound diagnoses, and definitive diagnoses after
      autopsy. MATERIAL AND METHODS: The survey was designed as a retrospective study
      and included 24 pregnant women who were attending a regular ultrasound
      examinations at the Department of Gynecology and Obstetrics, Clinical Center of
      Serbia, or patients who were referred from other institutions in Serbia. RESULTS:
      Neural tube defects are divided into five subgroups: spina bifida, meningocele,
      myelomeningocele, acranius, and anencephaly. The most frequent in the present
      study was spina bifida with 67%. All pregnancies complicated with neural tube
      defects were terminated. CONCLUSION: Their clinical severity and uncertain cause
      make them priorities for further research, whether to better target primary
      preventive measures, to improve in-utero surgery for prenatal repair, or to
      identify the causative genes to provide an objective basis for individual genetic
      counselling.

PMID- 25864284
TI  - Changes and clinical significance of peripheral blood helper T lymphocyte and
      natural killer (NK) cells in unexplained recurrent spontaneous abortion (URSA)
      patients after abortion and successful pregnancy .
AB  - OBJECTIVE: This study aims to investigate the number changes and the clinical
      significance of the peripheral blood T lymphocyte subsets and NK (natural killer)
      cells in unexplained recurrent spontaneous abortion (URSA) patients before and
      after abortion, as well as after successful pregnancy. MATERIALS AND METHODS:
      Thirty-nine URSA patients (URSA-abortion group), among who 22 patients were
      followed up until the final successful parturition (URSA-pregnancy group), 31
      normal-pregnancy (NP) cases and 25 normal non-pregnancy (NNP) control cases in
      which the peripheral blood T lymphocytes and subsets, B cells, and NK cells were
      assessed flow cytometry. RESULTS: Compared with the URSA-pregnancy group and the
      NP group, the Th cells and NK cells of the URSA-abortion group increased (p <
      0.05); compared with the NNP group, the total number of T cells decreased after
      the first, second, and third month of the URSA abortion (p < 0.05); Th cells
      decreased within one to six months of the URSA abortion (p < 0.05); proportion of
      NK cells was significantly higher in URSA patients (p < 0.05). CONCLUSION: The
      abnormal numbers of the peripheral blood T cell subsets and NK cells were related
      with the occurrence of URSA.

PMID- 25864285
TI  - Ruptured ipsilateral ectopic pregnancies: a rare emergency case series.
AB  - Ectopic pregnancy is one of the most important causes of maternal mortality in
      first trimester pregnancy. Several etiologic factors are suspected for ectopic
      pregnancy. Fertility-saving surgery in ectopic pregnancy is associated with
      recurrent ectopic pregnancy. Most common site of ectopic pregnancy is in the
      fallopian tube, especially in the ampullar region. Ipsilateral tube is rare site
      for ectopic pregnancy. Previous tubal surgery, especially partial salpingectomy,
      is an important factor in this disease.

PMID- 25864286
TI  - Cervical ripening agent dinoprostone for delivery induction in late pregnancy
      mothers: experiences of 685 cases.
AB  - The failure of labor induction often requires following cesarean section and
      suffering of patients. Cervical ripening is therefore critical in clinical care
      of pregnant mothers. The present study demonstrated the use of dinoprostone in
      cervical ripening for delivery induction in 685 cases of pregnancy mothers. The
      authors conclude that dinoprostone is a very useful and safe drug for delivery
      induction. The combined use of oxytocin and careful monitoring of all body
      symptoms are important for the clinical safety.

PMID- 25864287
TI  - Essure microinsert hysteroscopic tubal sterilization: eight-years follow-up
      results.
AB  - OBJECTIVES: To evaluate the effectiveness and reliability of microinsert
      hysteroscopic sterilization method at short- and long-term. MATERIALS AND
      METHODS: In the period between January 2004 and December 2005, 34 patients who
      submitted to the present gynecology outpatient clinic seeking for permanent
      contraception and accepted tubal sterilization with microinsert method were
      included in this prospective, interventional study. RESULTS: Bilateral
      microinsert placement was successful in 28 (87.5%) of 32 patients that underwent
      the procedure. In all of the 30 patients (100%) in whom the placement procedure
      was attempted, bilateral tubal occlusion was documented by hysterosalpingogram
      (HSG) including the two patients in whom unilateral placement was carried out.
      First three procedures were performed under general anesthesia. Local or general
      anesthesia was not administered in any other cases (97.5%). The mean visual
      analogue scale score for pain felt during the procedure was 3.1. The mean
      procedure time was 11.5 +/- 4.88 (5-22) minutes, the average time from beginning
      the procedure to discharge of the patients was 41.7 +/- 18.5 (15-94) minutes. One
      intrauterine pregnancy was detected in one of the patients nine months after
      cessation of the alternative contraceptive period. This patient was excluded from
      the follow-up. At short-term all patients rated their microinsert-wearing
      tolerance as good or excellent. At eighth year, three patients were lost to
      follow-up. Mean follow-up time was 83.4 +/- 15.0 (36-103) months. During 2,420
      woman-months of follow-up, no other pregnancies were detected. Almost all of the
      patients were happy with the procedure and recommended it to a friend.
      CONCLUSION: Essure microinsert is a safe, effective, minimally invasive
      sterilization method which can be performed in outpatient settings without any
      anesthesia requirement. It appears to be a good alternative to laparoscopic tubal
      sterilization. The procedure time and the time to discharge are brief. Patient
      tolerance during the procedure and at long-term is very good.

PMID- 25864288
TI  - The effect of calcium channel blockers on prevention of preeclampsia in pregnant
      women with chronic hypertension.
AB  - BACKGROUND: Pregnant women with chronic hypertension are at increased risk for
      complications. This study aims to investigate whether calcium channel blockers
      plus low dosage aspirin therapy can reduce the incidence of complications during
      pregnancy with chronic hypertension and improve the prognosis of neonates.
      MATERIALS AND METHODS: From March 2011 to June 2013, 33 patients were selected to
      join this trial according to the chronic hypertension criteria set by the Preface
      Bulletin of American College of Obstetricians and Gynecologists, (ACOG). Patients
      were administrated calcium channel blockers plus low-dosage aspirin and vitamin
      C. The statistic data of baseline and prognosis from the patients were
      retrospectively reviewed and compared. RESULTS: Blood pressure of patients was
      controlled by these medicines with average systolic pressure from 146.3 to 148.7
      mmHg and average diastolic pressure from 93.8 to 97.9 mmHg; 39.4% patients
      complicated mild preeclampsia; however, none of them developed severe
      preeclampsia or eclampsia, or complicate placental abruption. 30.3% patients
      delivered at preterm labour; 84.8% patients underwent cesarean section. The
      neonatal average weight was 3,008 +/- 629.6 g, in which seven neonatal weights
      were less than 2,500 g. All of the neonatal Apgar scores were 9 to 10 at one to
      five minutes. Small for gestational age (SGA) occurred in five (15%).
      CONCLUSIONS: Calcium channel blockers can improve the outcome of pregnancy women
      with chronic hypertension to avoid the occurrence of severe pregnancy
      complication or neonatal morbidity.

PMID- 25864289
TI  - Assessment of perioperative, early, and late postoperative complications of the
      inside-out transobturator tape procedure in the treatment of stress urinary
      incontinence..
AB  - OBJECTIVE: To evaluate the complications of urinary incontinence surgery with
      transobturator tape (TVT-O) system and to describe its diagnosis and management.
      MATERIALS AND METHODS: A total of 156 patients who were diagnosed as having
      stress incontinence and mixed incontinence with stress predominance underwent a
      TOT operation under spinal anesthesia by one surgeon or two surgeons (MB, AEY)
      from the team. TVT-obturator inside out material was used in the operation.
      Urodynamic tests and pad tests were done on all the patients. This is a
      prospective and retrospective study of the complications of TVT-O. The operation
      was performed under regional anesthesia, as described by Deval et al. Patients
      were excluded from the study if they had been operated under general or local
      anesthesia, had undergone any vaginal operations except for anterior repair
      (cystocele), wanted to have a baby, had severe systemic diseases or had been
      diagnosed as having urge incontinence in urodynamic tests. These situations may
      affect the rate of complications, the authors also excluded slings that had
      materials other than monofilament polypropylene, and patients who were suspected
      of having neurologic bladder conditions. The bladder and urethra were evaluated
      using cystoscopy. The durations of the TOT procedure, cystoscopy, and if
      performed, the cystocele operation, were recorded. Perioperative, early, and late
      postoperative complications were analyzed by follow-up visits (after two months
      to four years). RESULTS: Of the 156 patients included in the study, 100 (64.1%)
      had pure stress urinary incontinence and 56 (35.9%) had mixed incontinence, 20
      (12.8%) had previous incontinence surgery. The mean duration of follow up was
      30.3 +/- 7.4 (range 17-42) months. The mean age of the patients was found to be
      48.43 +/- 6.24 years (range 42-68). The mean parity of the patients was 5.24 +/-
      2.86 (range 2-13), and mean body mass index was found to be 23.7 +/- 4.8. Mean
      maximum detrusor pressure was 10.30 +/- 4.08 and the mean ALP value was 80.80 +/-
      25.57. Mean operative time was found to be 13.8 +/- 5.16 min in patients who
      underwent only TOT and TOT-anterior repair. Vaginal injury including to the
      lateral fornix (4.4%), hemorrhaging of more than 200 ml (3.2%), vascular damage
      (1.9%), hematoma on the leg (1.9%), hemorrhaging of more than 500 ml (0.064%),
      and bladder perforation (1.2%) were detected as perioperative complications.
      Urethral injury and perioperative nerve and intestinal injury did not occur. The
      most common complication in early postoperative period was inguinal pain
      extending the legs (30.7%), followed by headaches (23.7%), fever (12.8%), urinary
      tract infection (5.7%), and urinary retention (3.2%), respectively. Late
      postoperative complications included vaginal erosion (4.4%), de novo urge
      incontinence (8.9%), de novo dyspareunia (7.1%), perineal pain (4.4%), and
      worsening urgency (8.9%). CONCLUSION: Although the TVT-O technique is a minimal
      invasive surgery method applied to treat the urinary incontinence surgically, it
      does not imply that it is a complication-free surgical procedure. Despite the low
      incidence of intraoperative complications, there is a mild risk of early and late
      postoperative complications. Fortunately these complications can be taken under
      control by either conservative and simple medical treatments or surgical
      procedures.

PMID- 25864290
TI  - Post-partum management in a patient affected by thrombotic thrombocytopenic
      purpura: case report and review of literature.
AB  - Thrombotic thrombocytopenic purpura (TTP) is a rare and potentially lethal
      syndrome characterized by severe thrombocytopenia, microangiopathic haemolytic
      anaemia, and aspecific neurologic symptoms. This syndrome is the result of an
      abnormal intravascular platelet aggregation which induces transient ischemia in
      various organs, especially in the central nervous system. Platelet aggregation
      causes also fragmentation of erythrocytes, thus leading to the characteristic
      anaemia. The exact cause of TTP is unknown, but a large body of evidence suggest
      that this syndrome might be due to acquired (immunological) or congenital
      ADAMTS13 deficiency. The dysregulation of ADAMTS 13 activity could promote
      massive release of high molecular weight multimers of von Willebrand factor (VWF)
      from endothelium and, as a consequence, could cause intravascular platelet
      aggregation. Pregnancy is commonly associated with numerous metabolic,
      immunological, and haemostatic changes which could increase thrombotic risk:
      during pregnancy, in fact, it is generally observed an increase of procoagulant
      activity and a decrease of fibrinolytic activity; moreover, at the end of
      pregnancy, it is not rare to find thrombocytopenia. All these reasons lead us to
      consider pregnancy itself as a triggering event for the onset of TTP. The authors
      describe a case of TTP occurred during puerperium, in a patient who underwent
      caesarean section.

PMID- 25864291
TI  - Investigation of short- and long-term effects of ovarian hyperstimulation
      syndrome on ovarian reserve: an experimental study.
AB  - PURPOSE: To investigate the short and long-term effects of ovarian
      hyperstimulation syndrome (OHSS) on serum levels of vascular endothelial growth
      factor (VEGF) and endothelin-1 and ovarian follicular reserve (OFR). MATERIALS
      AND METHODS: An experimental case-control study was conducted on a university
      animal laboratory with 20 immature (22-day-old) virgin female Wistar Albino rats.
      Firstly, rats were divided into two groups. Group 1 (n = 10): control and Group 2
      (n = 10): experimental OHSS induced rats. Secondly, Group 2 was randomly divided
      into two groups on the day of OHSS development (27th day) as follows: Group 3 (n
      = 5): 27-day-old OHSS induced rats and Group 4 (n = 5): 27-day-old OHSS induced
      rats supervised for seven days. Group 1 was divided into two groups to constitute
      age-matched controls as follows: Group 5 (n = 5): 27-day-old rats, Group 6 (n =
      5): 35-day-old rats. The comparisons of Group 3 vs Group 5 and Group 4 vs Group 6
      were performed. Main outcome measures were OFR, serum levels of VEGF, and
      endothelin-1. RESULTS: While the OFR and primordial follicle number (PFN) of
      Group 3 were significantly lower than those of Group 5 (p < 0.05); VEGF and
      endothelin-1 levels and atretic follicle number (AFN) were significantly higher
      in Group 3 compared to Group 5 (p < 0.05). In Group 4, PFN was significantly
      lower (p < 0.05) and AFN was significantly (p < 0.05) higher than Group 6.
      However, there were no statistically significant difference between Group 4 and
      Group 6 regarding the parameters of OFR, serum levels of VEGF, and endothelin-1.
      CONCLUSION: This experimental OHSS model revealed increased serum VEGF and
      endothelin-1 levels and decreased OFR during short-term of OHSS. OHSS showed
      detrimental effect on PFN of rats during long-term.

PMID- 25864292
TI  - Massive haemorrhage secondary to placenta percreta in the first trimester: a case
      report.
AB  - Placenta percreta detected in the first trimester is a very rare condition. It is
      a known obstetric condition leading to serious maternal morbidity and mortality.
      High index of clinical suspicion and anticipation of placenta percreta is highly
      essential in early pregnancy as it is difficult to diagnose. The authors report
      on a patient who presented with heavy pervaginal bleeding in week 9 of pregnancy.
      Pelvic examination showed a 12-week sized uterus. Ultrasonography revealed a non
      viable fetus. The subsequent emergency curettage performed was complicated by
      massive haemorrhage which required an abdominal hysterectomy performed as a life
      saving procedure.

PMID- 25864293
TI  - Late postpartum hemorrhage due to placental and fetal membrane residuals:
      experience of two cases.
AB  - PURPOSE: To investigate the cause and preventative measures of late postpartum
      hemorrhage resulted from placental and fetal membrane residuals. MATERIALS AND
      METHODS: Retrospective analysis on 161 cases of late postpartum hemorrhage
      resulting from residuals of placenta and fetal membrane from 2002 to 2012.
      RESULTS: Among the 161 cases, there were 148 cases of vaginal delivery and 13
      cases of cesarean section delivery. One hundred twenty-one cases (4.77%) of
      placental and fetal membrane residuals were present in 2,535 cases of pregnant
      women with history of abortion; 40 cases (2.01%) of placental and fetal membrane
      residuals were found in 1,989 cases of pregnant women without history of
      abortion. CONCLUSION: Placental and fetal membrane residuals are the major cause
      of late postpartum hemorrhage. Repeated abortion will increase the incidence of
      late postpartum hemorrhage resulting from placental and fetal membrane residuals.

PMID- 25864294
TI  - Intrauterine endometriotic cyst at the site of previous cesarean scar; scar
      endometriosis.
AB  - Uterine scar endometriosis is an extremely rare entitiy. As the surgical
      procedures of the uterus increases through time, scar endometriosis may be
      diagnosed more often in the future. A case of uterine scar endometriosis is
      presented with complaints of menstruation lasting one day with associated pelvic
      pain. When a cystic mass in the site of previous surgery is diagnosed, scar
      endometriosis must be considered.

PMID- 25864295
TI  - Successful pregnancy and breastfeeding in a woman with mucopolysaccharidosis type
      I while receiving laronidase enzyme replacement. therapy.
AB  - The authors describe the first mother-infant pair to complete an on-going,
      prospective, open-label, Phase 4 trial (ALIU) UU3, NCT00418821) determining the
      safety of laronidase enzyme replacement therapy (ERT) in pregnant women with
      mucopolysaccharidosis type I (MPS I) and their breastfed infants. The mother, a
      32-year-old with attenuated MPS I (Scheie syndrome), received laronidase for
      three years and continued treatment throughout her second pregnancy and while
      lactating. A healthy 2.5 kg male was delivered by elective cesarean section at 37
      weeks. He was breastfed for three months. No laronidase was detected in breast
      milk. The infant never developed anti-laronidase IgM antibodies, never had
      inhibitory antibody activity in a cellular uptake assay, and always had normal
      urinary glycosaminoglycan (GAG) levels. No drug-related adverse events were
      reported. At 2.5 years of age, the boy is healthy with normal growth and
      development. In this first prospectively monitored mother-infant pair, laronidase
      during pregnancy and breastfeeding was uneventful.

PMID- 25864296
TI  - Successful management of discordant alobar holoprosencephaly in monochorionic
      diamniotic twins with normal karyotype: a case report.
AB  - Holoprosencephaly (HPE), a complex brain malformation resulting from incomplete
      cleavage of the prosencephalon into distinct cerebral hemispheres, is rare in
      newborns. Two preterm male neonates were born at 34 weeks' and five days'
      gestation in the monochorionic diamniotic twin pregnancy complicated with pre
      eclampsia and intrahepatic cholestasis of pregnancy, and one of them was
      prenatally diagnosed with alobar HPE by ultrasonography with frontal bossing,
      hydrocephaly, hypotelorism of eyes, flat nasal bridge, macroglossia, and
      cheilo/palatoschisis at birth. Karyotyping by G-banding of amniocentesis
      specimens in normal twin and fetal umbilical blood in both fetuses showed 46, XY.
      This report expands discordant alobar holoprosencephaly in monochorionic
      diamniotic twins.

PMID- 25864297
TI  - Holistic dentistry: history and portrayal by the media.

PMID- 25864298
TI  - I never lie.

PMID- 25864299
TI  - Computer-guided implant surgery: placing the perfect implant.

PMID- 25864300
TI  - The 10-year evolution of guided surgery.
AB  - The evolution of surgical techniques and fine-tuning of surgical methodology have
      allowed for more predictable results and esthetic outcomes. Examination of and
      reflection upon the evolution of guided surgery has allowed practitioners to
      refine the guided implant surgery procedure. The extent of the precision for
      recognizing anatomical landmarks, for implant placement and for restorative
      procedures allows clinicians to obtain more predictable results, which can lead
      to increased implant and prosthesis success and ultimately patient satisfaction.

PMID- 25864301
TI  - Digitally enhanced dentistry: the power of digital design.
AB  - New digital processes are used in treatment planning for implants and design and
      manufacture of surgical guides, abutments, provisionals and final restorations.
      The multiple technologies of 3-D cone beam CT imaging, intraoral scanning,
      laboratory scanning, 3-D digital restorative design and CAD/CAM production have
      contributed to this trend. Simultaneously, restorative materials have been
      introduced that have improved strength and esthetic qualities. Integration of
      these capabilities creates opportunities for enhanced restorative performance,
      decreased costs and improved practice efficiency.

PMID- 25864302
TI  - A simple, safe and affordable cast-based guided implant placement system.
AB  - A fully restrictive surgical guide allows controlled execution of a
      preoperatively planned osteotomy and subsequent implant placement. There are two
      fabrication modes. One is a digital path, where these guides can be fabricated
      based on data from a cone beam CT source. Alternatively, 3-D data can be derived
      from a dental cast and periapical radiographs. The 3D Click Guide is a cast
      based, fully restrictive surgical guide that can be generated in the dental
      office.

PMID- 25864303
TI  - Smart and simple steps to manage patient injuries.

PMID- 25864304
TI  - Electrical safety violations.

PMID- 25864305
TI  - Role of mechanical forces in the stomach phase on the in vitro bioaccessibility
      of B-carotene.

PMID- 25864306
TI  - Towards a lattice-free three-dimensional fungal growth model.

PMID- 25864307
TI  - A model based approach towards environment-specific field management strategies
      for upgrading crop water productivity.

PMID- 25864308
TI  - Modelling microbial community dynamics in a nitrifying biofilm--effect of the
      nitrogen loading rate.

PMID- 25864309
TI  - Animal migration modeling: an analytical description of the two-dimensional time
      integrated Brownian bridge.

PMID- 25864310
TI  - How to use mid-infrared spectral information from milk recording system to detect
      the pregnancy status of dairy cows.

PMID- 25864311
TI  - Quantitative structure (inhibitory) activity relationship and molecular docking
      studies of phenolic acids to angiotensin-converting enzyme.

PMID- 25864312
TI  - Cold storage to overcome dormancy affects the carbon balance of azalea.
AB  - Flower bud dormancy in azalea (Rhododendron simsii) is broken by artificial cold
      treatment and this will have its consequences on carbon reserves and
      photosynthesis. The effect of cold storage at 7  degrees C on carbohydrate and
      starch content in leaves and flower buds of an early ('Nordlicht') and semi-early
      ('M. Marie) flowering cultivar was quantified. Carbon loss due to respiration was
      lowest for 'M. Marie'. Photosynthetic measurements on 'Nordlicht' showed that
      photosynthesis 3 days after cold treatment (plants ready to flower) was improved
      compared to before cold treatment (plants with dormant flower buds).

PMID- 25864313
TI  - 'Organic growing medium inhibits the crazy roots syndrome: a case study with
      solanum melongena'.

PMID- 25864314
TI  - Plant-water relations of the mangrove species Rhizophora stylosa: a unique story.

PMID- 25864315
TI  - Canthaxanthin, astaxanthin and adonixanthin production from a dactylococcus
      microalga in a new flat plate airlift photobioreactor.

PMID- 25864316
TI  - Effect of low birth weight on the small intestinal defence function in neonatal
      piglets.

PMID- 25864317
TI  - A volatile sex pheromone in the invasive ladybeetle, Harmonia axyridis (Pallas)
      (Coleoptera: Coccinellidae).

PMID- 25864318
TI  - Repeated selection of Arabidopsis thaliana under heat stress.

PMID- 25864319
TI  - Effect of nitrite pulses on N20 production during nitrification.

PMID- 25864320
TI  - Yearly follow-up of methane turbulent exchange over an intensively grazed pasture
      in Belgium.

PMID- 25864321
TI  - Parameter study on the efficiency of ozonation for biologically treated landfill
      leachate.
AB  - Ozonation was investigated as a potential post-treatment step for biologically
      treated landfill leachate to enhance the biodegradability and observe the
      influence of the initial organic matter concentration and pH. Changes in COD, UV
      absorption at 254 nm (UVA254) and BOD content were measured during and after
      ozonation, and the ozone utilisation efficiency at different conditions was
      calculated. The initial COD concentration was found to influence the absolute
      removal of UVA254 significantly, but especially changes in pH influenced the
      ozone reactions. Increased pH (pH 10) most probably increased the overall
      hydroxyl radical production leading to a higher COD removal and a much better
      ozone utilisation compared to lower pH. This in contrast to initial COD
      variations which had little influence on the determined ozone utilisation.
      Regardless of initial COD content or pH, on average 10% of the initial COD
      content was converted to BOD, next to 10% COD that was removed.

PMID- 25864322
TI  - Soil organic carbon balance in a bio-energy plantation (POPFULL).

PMID- 25864323
TI  - The growth zone of maize leaves subjected to drought stress offers unique
      possibilities to confirm transcriptome analysis with cellular, physiological and
      biochemical measurements.

PMID- 25864324
TI  - A high performance computing approach for genomic prediction.

PMID- 25864325
TI  - Phenotyping Belgian Blue cattle for their susceptibility to psoroptic mange.

PMID- 25864326
TI  - Genotype X feed interactions in the genetic evaluation of Pietrain Boars.

PMID- 25864327
TI  - Physico-chemical properties and aroma profile of acacia honey produced in
      Romania.

PMID- 25864328
TI  - Psychrotrophic lactic acid bacterium (LAB) contamination: a spoilage problem for
      cold-stored and packaged food products.

PMID- 25864329
TI  - Comparing the impact of high pressure high temperature and thermal sterilization
      on the volatile fingerprint of onion, potato, pumpkin and red beet.

PMID- 25864330
TI  - Fourteen days cyclic heat challenge and feeding oreganum compactum and curcuma
      xanthorrhiza essential oils: effects on antioxidant system of broilers.

PMID- 25864331
TI  - Development of a colorimetric method for the dosage of OI- anions and I2 in
      aqueous media.
AB  - Lactoperoxidase catalyzes the oxidation of thiocyanate (SCN-) and iodide (I-) in
      presence of hydrogen peroxide in hypothiocyanite (OSCN-) ions and, depending on
      the pH, in hypoiodite (OI-) ions or in iode (I2). Oxidized SCN- and I- are part
      of the lactoperoxidase system, which is a natural biological protection in cow
      milk, and are described as having inhibitory properties against pathogenic human
      bacteria, fungi and viruses. We have developed an aqueous solution containing
      only OSCN- and OI- ions (without the enzyme) and we tested it successfully
      against plant pathogens. In order to characterize this new soft chemical control
      against plant pathogens we had to determine the concentration of OSCN- and OI-
      ions. The dosage of OSCN- consists in a well referenced colorimetric method but
      no procedure is described for the determination of OI- ions. We have thus
      developed an easy method, based on the oxidation of the amine moiety of 3,3',5,5'
      tetramethylbenzidine (TMB) by OI- or I2 in a strongly absorbing blue product for
      the detection and dosage of both molecules. Interestingly the OSCN- ions are not
      able to oxidize TMB and render this method specific to enzymatic oxidized iodide.
      We have calculated its sensitivity, repeatability and linearity. This method
      could also be used for the determination of OCI- and OBr- ions produced during
      the enzymatic oxidation of chloride and bromide by mammalian's peroxidases.

PMID- 25864332
TI  - Implementation of a metal structured packing in a fungal biofilm reactor for the
      production of a recombinant protein by Aspergillus oryzae.

PMID- 25864333
TI  - Plasmid transfer in biofilms from a food industry perspective.

PMID- 25864334
TI  - Spatial and temporal differences in degradation characteristics and microbial
      community composition of pesticide biopurification systems.

PMID- 25864335
TI  - Using micro-injection technique to assess fungal toxicity in mosquito control.

PMID- 25864336
TI  - Functional differences of storage proteins are reflected in their mobilization
      patterns from protein bodies in cotyledon cells during olive (Olea europaea L.)
      seed germination.

PMID- 25864337
TI  - Habitat suitability modelling in auto-ecology analysis of Azolla filiculoides
      (Lam.) azollaceae in Selkeh wildlife refuge (Iran).

PMID- 25864338
TI  - Analysis of environmental factors determining distribution pattern of Azolla
      filiculoides (Lam.) azollaceae in Anzali wetland, northern Iran.

PMID- 25864339
TI  - Effect of dog breed 'varieties' on population genetic structure.

PMID- 25864340
TI  - [Pharmacotherapy for irritable bowel syndrome in the context of evidence-based
      medicine].
AB  - The paper analyzes an evidence base for the pharmacotherapy of irritable bowel
      syndrome (IBS) A large number of randomized placebo-controlled trials (RPCTs)
      systematized in a number of meta-analyses suggest that monotherapy regimens with
      spasmolytics, antidepressants, dietary fibers, polyethylene glycol, rifaximin,
      probiotics, and mesalamine are effective. Only some RPCTs evaluate the efficiency
      of combined pharmacotherapy versus placebo for IBS. Since the basis for the
      pathophysiology of the latter is motility and functional disorders, visceral
      hypersensitivity, and, probably, impaired microbiota, we anticipate that the need
      to use combined approaches to treating the majority of patients with IBS, by
      covering a few components of its pathogenesis, is relevant. Thus, to choose
      pharmacotherapy for IBS in each specific case is a challenge as this is
      determined by the form of IBS, the availability of an approved medicine on the
      domestic market, the indications for use, possible long-term use, high safety,
      and efficacy evidence drawn from RPCTs.

PMID- 25864341
TI  - [Indicators of apoptosis in the gastric mucosa in patients with atrophic
      gastritis among the indigenous and nonindigenous dwellers of Evenkia].
AB  - AIM: To study the indicators of apoptosis in the gastric mucosa (GM) in relation
      to atrophy and the presence of CagA gene- containing Helicobacter pylori strains
      in the indigenous and nonindigenous dwellers of Evenkia. SUBJECTS AND METHODS:
      Clinical and morphological examinations and fibrogastroscopy of GM were performed
      in 159 Caucasians and 136 Mongoloids (Evenks). The TUNEL assay was used to
      determine GM apoptosis in 24 Caucasians and 22 Evenks and the H. pylori strains
      containing the CagA gene were detected in all the 295 patients. RESULTS: The
      extent of atrophic gastritis in the gastric antrum and body was higher in the
      Caucasians than in the Evenks. The total indicator of GM apoptosis in the gastric
      antrum was 5.19 +/- 0.26% in the newcomers and 4.04 +/- 0.28% in the aboriginals
      (p = 0.01). Apoptosis in both populations was associated with GM atrophy and the
      presence of H. pylori strains containing CagA gene. CONCLUSION: There were ethnic
      differences in the extent of atrophic gastritis, which may be attributable to
      differences in the rate of GM apoptosis and the spread of H. pylori strains
      containing CagA gene in the indigenous and non-indigenous dwellers of Evenkia.

PMID- 25864342
TI  - [Clinical and pathogenetic features of inflammatory and atrophic changes in the
      gastroduodenal zone in patients with varying severity of chronic heart failure
      associated with coronary artery disease].
AB  - AIM: To study the clinical features of inflammatory and atrophic changes (IAls)
      in the gastroduodenal zone (GDZ) in people with varying severity of chronic heart
      failure (CHF) associated with coronary artery disease (CAD) and to determine
      gastric secretion, local microcirculation, and the presence of Helicobacter
      pylori. SUBJECTS AND METHODS: Seventy-four patients with CHF and gastric duodenal
      (GD) IAls who were divided into 2 groups according to its severity were examined.
      The specific features of impaired gastric secretory function and blood flow in
      the GD mucosa and its contamination with H. pylori were elucidated. RESULTS: GD
      IAls were ascertained to be mainly focal in the patients with Stages I-Ila CHF
      and focal or diffuse in those with Stages IIb-III. According the clinical
      findings, these changes were generally shown in the concurrence of transient and
      unstable (in early- stage circulatory insufficiency) and prolonged and persistent
      (during severe congestive events) phenomena. The development of IAls in the GDZ
      was linked to its thrombohemorrhagic microcirculatory disorders, the severity of
      which increased as the symptoms of CHF progressed. In Stages I-Ila circulatory
      insufficiency, this was accompanied by the normal activity of acid-peptic factor,
      by the decreased production gastromucoproteins, and, in 58.3% of cases, by H.
      pylori. The patients with Stages IIb-III showed the suppressed production of all
      constituents of gastric secretion and H. pylori in 63.2% of cases. CONCLUSION:
      The clinical manifestations and mechanisms of GD IAIs in CHF associated with CAD
      have a number of substantial differences in relation to its severity, which
      should be kept in mind when elaborating therapeutic and diagnostic measures.

PMID- 25864343
TI  - [Small intestinal bacterial overgrowth as a cause of lactase deficiency].
AB  - AIM: To establish the rate of lactase deficiency (LD) in patients with post
      infectious irritable bowel syndrome (PI-IBS), to define a role of enteric
      bacteria in the pathogenesis of hypolactasia, and to evaluate the efficiency of
      probiotic therapy. SUBJECTS AND METHODS: Examinations were made in 386 patients
      with PI-IBS, including 112 (79.4%) women; mean age 33.9 +/- 9.1 years; disease
      duration 2.6 +/- 1.4 years. Rapid tests of small intestinal mucosa (SIM) biopsy
      specimens obtained from the duodenal retrobulbar segment were used to diagnose
      LD. Bacterial growth was estimated by a hydrogen breath test using a H2 MICRO gas
      analyzer. RESULTS: The patients with PI-IBS were revealed to have moderate and
      severe LD in 25.6 and 10.9%, respectively. All the patients with LD were detected
      to have small intestinal (SI) bacterial overgrowth (BOG). An inverse correlation
      was found between LD and the degree of SI BOG (r = -0.53; p < 0.001). 73.7% of
      the patients with moderate LD showed a positive effect of probiotic therapy as
      regression of clinical symptoms of LD, a decrease of hydrogen levels in expired
      air from 72.4 +/- 25.1 to 16.41 +/- 3.2 ppm (p < 0.05), an increase of lactate
      activity in the SIM biopsy specimens and an improvement of quality of life from
      2.69 +/- 0.53 to 5.53 +/- 0.64 scores according to the GCI scale. No improvement
      occurred in 73.8% of the patients with severe LD. CONCLUSION: LD was identified
      in 36.5% of the patients with PI-IBS. There was an inverse correlation between
      the degree of LD and SI BOG. The good therapeutic effect of probiotics in LD
      suggests that the symbiotic gut microflora positively affects the activity of
      lactase in the human SIM. No therapeutic effect of probiotics in patients with
      severe LN serves as the basis for a search for more active probiotic therapy.

PMID- 25864344
TI  - [Carbohydrase activities may serve as a marker for small intestinal mucosal
      recovery in patients with celiac disease].
AB  - Aim. To clinically evaluate the activity of glucoamylase, maltase, saccharase,
      and lactase in the small intestinal mucosa (SIM) of patients with celiac disease.
      Subjects and methods. Twenty-nine patents with celiac disease were examined. The
      disease was first detected in 8 patients; in the remaining patients, it had been
      diagnosed 6 months to 35 years before. The diagnosis was verified by histological
      examinations of duodenal biopsy specimens and by determination of immunoglobulin
      (Ig) A and G antibodies to tissue transglutaminase (atTG) and gliadin (AGA) by an
      enzyme-linked immunosorbent assay (ELISA). Carbohydrase activities were estimated
      in the duodenal biopsy specimens, by applying the method of A. Dahlquist.
      Results. In the control group, the activities of glucoamylase, maltase,
      saccharase, and lactase averaged 598.8+184.2, 825.3+239.3, 180.2-68.1, and
      53.4+16.3 ng/glucose/mg tissue min, respectively. In the patients with celiac
      disease, the average activities of all the examined enteric enzymes were
      significantly below the normal value even they had been on a gluten-free diet
      (GFD) for 10 years or longer. Complete SIM structural recovery (Marsh stage 0)
      occurred in only 7 of 18 patients who had been on a strictly GFD. Serological
      (atTG and AGA) tests got also negative in all the 7 patients with completely
      recovered SIM. Six of the latter patients continued to have abdominal bloating
      and borborygmus, unstable stool with a propensity for diarrhea and weakness. Each
      was detected to have a lower activity of one or a few enzymes. The activity of
      all the carbohydrases reached its normal value in only 1 patient and she felt
      healthy, without perceiving any food intolerance. Conclusion. The activity of
      membrane enzymes may serve as a marker for the degree of SIM recovery in patients
      with celiac disease.

PMID- 25864345
TI  - [Fecal calprotectin concentration in the differential diagnosis of bowel
      diseases].
AB  - AIM: To estimate the informative value of a noninvasive fecal (calprotectin) test
      in the differential diagnosis of bowel diseases. SUBJECTS AND METHODS: One
      hundred and forty-two patients who had visited their physicians with intestinal
      disorders (a change in stool frequency and patterns, abdominal pain) were
      examined in an open-label multicenter cross-sectional study. The examinees' mean
      age was 35 +/- 2.43 years. Gender- and age-matched comparison groups consisted of
      healthy individuals and patients with irritable bowel syndrome. Fecal
      calprotectin (FCP) was determined using a BUHLMANN Calprotectin ELISA kit. All
      the patients underwent colonoscopy. RESULTS: In the patients with organic bowel
      diseases (ulcerative colitis, Crohn's disease, lymphocytic colitis, colonic
      diverticular disease, colonic adenomas, celiac disease), the concentration of FCP
      was found to be substantially higher than that in the healthy individuals and
      patients with irritable bowel syndrome. The highest calprotectin levels were
      noted in the patients with inflammatory bowel diseases. CONCLUSION: This study
      demonstrated the high diagnostic value of the calprotectin test for the
      differential diagnosis of organic and functional bowel diseases.

PMID- 25864346
TI  - [Long-term results of medical treatment in patients with a severe attack of
      ulcerative colitis].
AB  - AIM: To assess the long-term result of medical treatment in patients with a
      severe attack (SA) of ulcerative colitis (UC). SUBJECTS AND METHODS: The course
      of UC was analyzed in 56 patients who were accessible by telephone contact and
      consecutively recruited for a year after therapy for a SA of UC. All the patients
      were stated to have a SA of UC according to the Truelove-Witts' criteria; they
      received therapy with intravenous glucocorticosteroids (GCS) (prednisolone 2
      mg/kg) along with anti-recurrence therapy with mesalasine (5-ASA) or azathioprine
      (AZA). Ten (17.9%) GCS-resistant patients were given infliximab (INF) (5 mg/ kg),
      followed by its maintenance infusions. Anti-recurrence therapy using 5-ASA, AZA,
      and INF was performed in 33 (58.9%), 13 (23.2%), and 10 (17.9%) patients,
      respectively. RESULTS: During one year, 14 (25%) patients continued to be in
      clinical remission on maintenance therapy or to have attacks stopped without
      using GCS, immunosuppressive agents, or INF (a satisfactory response group).
      Colectomy was carried out in 23 (41.1%) patients; due to recurrent UC when
      decreasing the dose of GCS, 5 (8.9%) patients continued to take the latter during
      a year. A GCS cycle was repeated in 3 patients who had received AZA (the basic
      therapy was not corrected) and 11 patients who had taken 5-ASA. The prognostic
      factors for a long-term result of medical therapy included the choice of AZA as
      an anti-recurrent drug (57.1 and 11.9% in the satisfactory and poor treatment
      outcome groups, respectively; p = 0.004) and patient age (34.4 and 42.8 years,
      respectively; p = 0.0357). CONCLUSION: During 1 year after a SA of UC,
      indications for colectomy and repeated GCS use occurred in 41 and 34% of the
      patients, respectively. The long-term efficiency of medical therapy for a SA of
      UC declines with advancing age. The use of AZA as an anti-recurrence agent after
      termination of GCS intake increases the probability of long-term clinical
      response.

PMID- 25864347
TI  - [Safety of mesenchymal stromal cell therapy for inflammatory bowel diseases:
      results of a 5-year follow-up].
AB  - AIM: To compare the safety of therapy in patients with ulcerative colitis (UC)
      and Crohn's disease (CD) who have received combination anti-inflammatory therapy
      using bone marrow mesenchymal stromal cells (MSC) and standard therapy with 5
      aminosalicylic acid, glucocorticosteroids, and immunosuppressive agents. SUBJECTS
      AND METHODS: Unfavorable consequences were analyzed in 103 patients (56 with UC
      and 47 with CD) with inflammatory bowel disease (IBD) after MSC administration.
      The findings were compared with data obtained in 208 patients with UC and CD on
      standard anti-inflammatory therapy. All the patients were similar in demographic
      parameters, the duration of disease, the extent of intestinal injury, the nature
      of a course, the type and degree of disease. The analyzed groups did not include
      patients who had received therapy with anti-TNF-alpha drugs. The safety of
      therapy was evaluated from the presence of complications occurring during the
      follow-up. RESULTS: By analyzing the unfavorable consequences in 103 patients
      with IBD and comparing them with treatment results in 208 patients with UC and CD
      on standard anti-inflammatory therapy, the authors revealed no differences in the
      development of acute posttransfusion reactions, infectious complications,
      exacerbations of chronic inflammatory diseases, severe infectious complications,
      malignant transformation, and fatal cases in patients with UC and CD, except for
      those with transient fever. CONCLUSION: The results of this study demonstrate
      that the innovative method of cell therapy is clinically safe.

PMID- 25864348
TI  - [Normative values for peripheral electrical gastroenterocolonography].
AB  - AIM: To elaborate the normative values of peripheral electrical
      gastroenterocolonography (EGECG). SUBJECTS AND METHODS: Fifty apparently healthy
      young people (14 women and 36 men; mean age 20.2 +/- 4.7 years) were examined.
      Peripheral EGECG was used to study the motor-evacuating function of the
      gastrointestinal tract (GIT). RESULTS: The values of the main indicators and
      coefficients of GIT electrical activity were defined; the concepts of normal
      physiological values for GIT electrical activity were identified and their values
      were determined. CONCLUSION: Peripheral EGECG makes it possible to significantly
      estimate the bioelectrical activity of the gut. The informative markers of
      peripheral EGECG are relative electrical activity, ratio coefficient, rhythmicity
      coefficient, as well as the average amplitude and frequency of bioelectrical
      activity.

PMID- 25864349
TI  - [Catalase gene rs1001179 polymorphism and oxidative stress in patients with
      chronic hepatitis C and ulcerative colitis].
AB  - AIM: To study the rs1001179 polymorphism of the catalase (CAT) gene and to
      estimate the serum levels of the enzymes catalase and glutathione peroxidase (GP)
      in patients with chronic hepatitis C (CHC) and in those with ulcerative colitis
      (UC) in the Perm Territory. SUBJECTS AND METHODS: Ninety patients with
      reactivation-phase CHC and 50 patients with exacerbation-phase UC were examined.
      The serum levels of catalase and GP were determined and the polymorphic variants
      of the marker of CAT gene rs1001179 in the DNA isolated from whole blood were
      found in all the patients. RESULTS: In the CHC and UC groups, the levels of
      catalase and GP were found to be lower than that in apparently healthy
      individuals. Furthermore, both groups showed a direct correlation between the
      activities of the enzymes. In the patients with CHC and in those with UC, the
      spread of genotypes and alleles generally failed to virtually differ from that in
      the control group. The G/G genotype was prevalent in all the groups. In the
      patients with CHC, the minor A allele demonstrated a significant inverse
      correlation with the enzyme catalase (r = -0.16; p = 0.02) and GP (r = -0.13; p =
      0.047). CONCLUSION: The lower serum levels of catalase and GP are indicative of
      oxidative stress in the patients with CHC or UC. In the patients with CHC, the
      significant correlation of the pathological rs1701179 A allele marker with the
      processes of synthesis of antioxidant enzymes may suggest that CAT gene
      polymorphism in the A/A homozygotes might affect the regulation mechanism
      involved in the antioxidant system in the liver.

PMID- 25864350
TI  - [Cholelithiasis as a possible manifestation of systemic digestive diseases].
AB  - AIM: To comprehensively study of the function of digestive organs in
      cholelithiasis (CL). SUBJECTS AND METHODS: Three hundred and seventeen patients
      with the early (prestone) stage of CL were examined. The latter was verified by
      ultrasonography (USG) and biochemical bile tests. The patients underwent pH metry
      and esophagogastroduodenoscopy, followed by histological examination of
      gastroduodenal mucosa (GDM) biopsy specimens. Manometry was used to evaluate
      duodenal function. The serum levels of pepsinogen-1 (PG-1), pepsinogen-2 (PG-2),
      cholecystokinin (CCK), gastrin, cyclic nucleotides (cAMP and cGMP), alpha1
      antitrypsin, insulin, and C-peptide were analyzed by an enzyme immunoassay. Small
      intestinal function was examined using a set of diagnostic tests. RESULTS:
      Gallbladder USG revealed biliary sludge in 273 (86.1%) patients. Biochemical
      examination of bile established a lower cholatocholesterol coefficient in its
      cystic as well as hepatic portions, suggesting enhanced bile lithogenicity.
      Manometry of the duodenum showed its hypertension, hypotension, and normotension
      in 57.6, 24.8, and 17.6% of the CL patients, respectively. There were significant
      increases in basal gastric body pH and PG-1 and PG-2 levels as compared to the
      control group. Morphological examination of GDM biopsy specimens revealed chronic
      superficial gastritis in 61.8% of the patients, chronic atrophic gastritis in
      17.4%, and moderate diffuse duodenitis in 18.3%. In 148 (46.7%) patients with CL,
      the latter was burdened by pancreatic comorbidity. Stress tests using water
      soluble starch, sucrose, and glucose demonstrated impairments in various stages
      of digestion; substantially decreased levels of CCK, gastrin and cyclic
      nucleotides were observed in the patients with CL compared to the controls.
      CONCLUSION: Most patients with CL were detected to have digestive organ
      structural and functional disorders. Moreover, CL may be regarded as a possible
      manifestation of systemic digestive diseases.

PMID- 25864351
TI  - [Capabilities of ultrasonic histography in the evaluation of the degree of
      pancreatic fibrosis in chronic pancreatitis].
AB  - AIM: To analyze the clinical and pathogenetic significance of ultrasonic
      histography in pancreatic fibrosis in patients with chronic pancreatitis (CP).
      SUBJECTS AND METHODS: One hundred and eighty-six patients with CP were examined.
      Complete blood count, urinalysis, biochemical blood and urine tests, duodenal
      intubation test, coproscopy, enzyme immunoassay, and radioimmune assay were
      performed. The levels of blood transforming growth factor beta1 (TGFbeta1) and
      fecal elastase-1 were measured. Ultrasonography and ultrasonic histography of the
      pancreas and liver, Doppler sound study of the abdominal aorta, celiac trunk, and
      superior mesenteric artery were carried out. RESULTS: There were correlations
      suggesting the decreased exocrine function of the pancreas as its fibrosis
      progressed, which was indirectly reflected in the increased L index of an
      ultrasonic histogram. The positive correlation between L index and TGFbeta1 also
      showed increased L index in more obvious pancreatic fibrosis. A CP exacerbation
      was shown to be accompanied by decreased Kgst and N, which was confirmed by
      pronounced hyperenzymenia (the blood enzyme release phenomenon) with the decrease
      of those indicators. Pancreatic fibrosis was reflected in the magnitude of
      clinical manifestations of CP, particularly in the rise of the number of
      dyspeptic complaints showing diminished pancreatic exocrine secretion. This was
      also supported by the fact that as the L index increased, the debit hour of
      lipase and the activity of fecal elastase-1 decreased. There were correlations
      pointing to more significant fibrosis of the pancreas and its insufficiency with
      worsened blood flow in it. Moreover, ultrasonic histographic findings accounted
      for a positive correlation between pancreatic and hepatic fibrosis. CONCLUSION:
      Examination of ultrasonic histographic correlations of the pancreas has led to
      the conclusion that this technique may be used to indirectly estimate the degree
      of pancreatic fibrosis and a CP exacerbation.

PMID- 25864352
TI  - [Hypertensive patients' adherence, motivation, and awareness during fixed-dose
      perindopril A and amlodipine combination treatment (results of the CONSTANTA
      trial)].
AB  - AIM: To estimate changes in treatment adherence and motivation and quality of
      life in Prestance-treated population of the observational CONSTANTA program.
      SUBJECTS AND METHODS: The effect of Prestance on treatment adherence and
      motivation and quality of life was evaluated in 2435 participants of the
      CONSTANTA program. It included patients with uncontrolled hypertension who
      generally received angiotensin-converting enzyme inhibitors or angiotensin II
      receptor antagonists alone or in conjunction with free or fixed-dose combinations
      of 2-3 antihypertensive agents and who were additionally given Prestance to
      correct antihypertensive therapy, as decided by their doctors. The goal blood
      pressure (BP) was less than <140/90 mm Hg for all the patients. A modified
      Morisky- Green questionnaire was used to measure adherence, motivation, and
      awareness in the patients. Their treatment lasted three months. RESULTS: A total
      of 1992 (81.8%) patients in the analyzed group achieved the goal BP. When
      included in the study, 1076 (44.2%) patients were defined as adherent to therapy;
      the mean adherence index was equal to 3.12 +/- 0.86 scores; at 3 months of
      therapy, the number of adherents increased up to 1997 (82%) and the mean
      adherence index rose up to 3.6 +/- 0.74 scores. With high baseline motivation,
      its mean score was 1.25 +/- 0.79 in 40.1% of the patients; at 3 months the number
      of the motivated rose up to 70.9% (p < 0.05) and the mean score was as high as
      1.75 +/- 0.60 (p < 0/05). At baseline, 44.2% of the patients showed a high
      awareness; its mean score was 1.42 +/- 1.12; at 3 months of therapy, both
      indicators significantly increased up to 82% (p < 0.05) and 2.38 +/- 0.80,
      respectively. CONCLUSION: The well tolerable BP lowering during Prestance therapy
      is attended by a substantial rise in treatment adherence and motivations in the
      patients even in the absence of special purposeful measures.

PMID- 25864353
TI  - [Impact of bariatric surgery on vitamin metabolisms in obese patients].
AB  - AIM: To investigate the impact of bariatric surgery (BS) on the level of vitamins
      in obese patients. SUBJECTS AND METHODS: One hundred obese patients (78 women and
      22 men) aged 19 to 61 years were examined. Controlled gastric banding (CGB) was
      carried out in 20 patients (mean body mass index (BMI), 41.3 +/- 8.2 kg/m2);
      gastric sleeve resection (GSR) in 40 patients, and gastric shunting (GS) in 40
      (the mean BMI in these groups were 41.1 +/- 17.8 and 45.9 +/- 6.2 kg/m2,
      respectively). A control group consisted of 10 apparently healthy individuals
      (BMI, 24.9 +/- 3.2 kg/m2). An enzyme immunoassay was used to determine the serum
      concentrations of vitamins B1, B2, B5, B6, B9, B12, C, and D, niacin, biotin, and
      retinol-binding protein (RBP) before and 1 year after surgery. RESULTS: All the
      three groups showed a considerable decrease in the levels of vitamins C, B5, B6,
      and D, and RBP both prior to and following BS. More than 50% of the patients who
      had undergone GSR had also a lower baseline niacin level. A year after CGB, GSR,
      and GS, the number of patents with deficiency of these vitamins remained the same
      or increased. The majority of patients with the same level of vitamin B2, niacin,
      and folic acid (FA) were observed to have its decrease a year postsurgery. The
      concentration of the other test vitamins was also reduced a year after all
      operations; however, it remained within the normal range. GS had no substantial
      impact on the concentrations of FA, vitamins B2, B12, B1, and biotin. The lower
      serum vitamin levels were not accompanied by clinical symptoms in most patients
      following BS. CONCLUSION: In 80% of the patients with obesity, the levels of
      vitamins C, B6, and D were decreased to a variable degree. After BS, there was a
      rise in the number of patients with low serum vitamin C, D, B6, B5, niacin, FA,
      and RBP concentrations, at the same time the number of patients with FA
      deficiency increased by more than twice. BS did not significantly affect the
      metabolism of vitamins B1 B2 B12, and biotin.

PMID- 25864354
TI  - [Complicated gastroesophageal reflux disease in the presence of congenital
      esophageal shortening].
AB  - The paper presents a clinical case of complicated gastroesophageal reflux disease
      (GERD) and describes problems in the differential diagnosis of malignant
      esophageal lesion in patients with GERD and a treatment modality used in this
      clinical case.

PMID- 25864355
TI  - [Eosinophilic enterocolitis: a clinical case].
AB  - The paper describes a clinical case of primary eosinophilic enterocolitis in a 41
      year-old female patent. It presents a brief review of the literature on the
      problem of primary eosinophil-associated gastrointestinal diseases.

PMID- 25864356
TI  - [Inadequate response to proton pump inhibitor therapy: causes and patient
      management tactics].
AB  - The past decade has been marked by a considerable increase in the number of
      patients with gastroesophageal reflux disease and gastroduodenal ulcer who show
      an inadequate response to proton pump inhibitor (PPI) therapy. At the present
      time, most of the causes diminishing the response have been elucidated.
      Unfortunately, they cannot always be eliminated by drug therapy; nonetheless,
      rabeprazole has a number of advantages over other PPIs. The major causes of an
      inadequate response to PPI therapy are low treatment motivation; nocturnal
      gastric acid breakthroughs; genetically determined CYP polymorphism; chiefly
      nighttime symptoms of gastroesophageal reflux disease; non-acid refluxes;
      hypersensitive esophagus; overweight and obesity.

PMID- 25864357
TI  - [Fortieth anniversary session of the Central Research Institute of
      Gastroenterology].

PMID- 25864358
TI  - [Chernin Vyacheslav Vasilyevich (on the occasion of the 80th anniversary of his
      birth)].

PMID- 25864359
TI  - [Schatzki ring as a symptom of gastroesophageal reflux disease].
AB  - OBJECTIVE: To determine the importance of a symptom of Schatzki ring. MATERIAL
      AND METHODS: The results of examining 95 patients aged 62-92 years with the
      symptoms of dyspepsia in the Netanya State Geriatric Center (Israel) in 1994-2004
      were analyzed. Standard X-ray study of the upper digestive tract was complemented
      by provocation tests. The length of an X-ray-negative area (XNA) between barium
      in the esophagus and stomach and the width in the lower esophagus were measured.
      RESULTS: Only 2 (2%) of the 95 patients were found to have normal function of the
      gastroesophageal junction (GEJ). Two patients with a drastic esophageal narrowing
      due to reflux esophagitis were excluded. The remaining (91) patients were divided
      into 2 groups. The width of the esophagus was less than 2 cm and 2 cm or more in
      64 (70%) and 27 (30%) patients, respectively. In weak GEJ, there was esophageal
      dilatation above the XNA. When in a horizontal position, this portion of the
      esophagus evacuates its contents into the stomach as a result of ampullary
      function. It is proximally closed by contracting the functional proximal
      sphincter (PS). When the ampulla contracts, its pressure increases up to the
      threshold. This causes the XNA to be closed and the ampulla to inject its
      contents into the stomach. The wider was the ampulla, the shorter the XNA was.
      Schatzki ring was detected in 20 (22%) of the 91 patients with gastroesophageal
      reflux disease (GERD). It was always at the level of the PS. CONCLUSION: The so
      called sliding esophageal hernia is an esophageal ampulla measuring more than 2
      cm in wide. The presence of the esophageal ampulla despite its size suggests that
      the GEJ is incompetent and GERD is present. Schatzki ring occurs at the level of
      the PS due to reflux esophagitis.

PMID- 25864360
TI  - [18F-FDG positron emission tomography in the diagnosis and staging of marginal
      zone non-Hodgkin lymphomas].
AB  - OBJECTIVE: To investigate the diagnostic value of 18F-FDG positron emission
      tomography (PET) in the diagnosis and staging of marginal zone non-Hodgkin
      lymphomas (NHLs). MATERIAL AND METHODS: Twenty-four patients with new-onset NHLs
      were examined. Extranodal MALT lymphoma, splenic marginal zone lymphoma (MZL),
      and nodal MZL lymphoma were diagnosed in 18, 3, and 3 patients, respectively. 18F
      FDG PET was carried out by the standard protocol via whole-body examination, by
      estimating the standardized tracer uptake value (SUV(max)) in the abnormal foci.
      RESULTS: Most (83.3%) of the examinees were found to have abnormal tracer
      hyperfixation foci. The mean SUV(max) was 5.05 +/- 0.9. There was no correlation
      between SUV(max) in the tumor foci and their metabolic sizes (r = 0.1; p = 0.7).
      No significant differences between the mean SUV(max) were found in patients with
      different histological types of MZL (p > 0.05). Disease staging by PET and other
      diagnostic methods yielded contradictory results in three patients. The final
      analysis suggested that the stage had been correctly determined in all the 3
      patients from PET findings. CONCLUSION: The results of 18F-FDG PET suggest that
      it is of high iagnostic value in imag-ng marginal zone NHLs. The major advantage
      of PET is that it can accu-ately stage the disease, which can provide a ra-ionale
      for optimal treat-ent policy.

PMID- 25864361
TI  - [X-ray densitometry investigation of bone mineral density in women: regional
      aspects].
AB  - OBJECTIVE: To calculate Z scores for different age groups of women in the
      Kemerovo region, by relying on the developed database for two-dimensional bone
      mineral densities (BMD) of the lumbar vertebra and proximal femoral bone.
      MATERIAL AND METHODS: This given investigation analyzed 1504 results of dual
      energy X-ray absorptiometry of the lumbar vertebra and proximal femoral bone in
      healthy women from the Kemerovo Region. RESULTS: The performed investigation
      revealed that the peak bone mass of the lumbar spine and proximal femoral bone in
      the Kuzbass women corresponded to that of 20-29-year olds. In the women of the
      Kemerovo Region, the population-based lumbar vertebral BMDs significantly
      differed from those available in the NHANES III database starting from 30 years
      of age. Thus, the developed BMD database has regional features and must be used
      to calculate a Z score for the female population of Kuzbass. By taking into
      account the fact that were no differences in the peak body mass values of the
      women in the two compared groups in accordance of the guidelines of the
      International Society for Clinical Densitometry; the NHANES III database may be
      used to estimate a T score.

PMID- 25864362
TI  - [Role of multislice computed tomography in the diagnosis of acute rupture of the
      thoracic aorta and hepatic artery in a patient with severe concomitant injury].
AB  - Acute traumatic aortic rupture is associated with extremely high mortality rates
      and requires emergency diagnosis and treatment. This clinical example shows the
      role of multislice spiral computed tomography in the emergency diagnosis of
      rupture of two large arterial vessels in severe concomitant injury. It presents
      the benefits of this rapid and noninvasive imaging technique, an algorithm of the
      study and the semiotics of injuries in patients with suspected traumatic aortic
      rupture. The paper also shows the importance of this method in defining treatment
      policy and then in the assessment of the results of the performed correction.

PMID- 25864363
TI  - [Clinical case of using manual thrombus aspiration during percutaneous coronary
      intervention in a patient with ST-segment elevation myocardial infarction type
      2].
AB  - The paper describes a patient admitted to the Emergency Cardiology Department,
      A.L. Myasnikov Institute of Clinical Cardiology, for diagnosed ST-segment
      elevation acute coronary syndrome. At the prehospital stage, the patient received
      ineffective thrombolytic therapy; percutaneous coronary intervention was made at
      the Department of X-ray Endovascular Diagnostic and Treatment Methods of the
      Institute 3.5 hours after disease onset. Repeated thrombus aspirations from the
      infarction-related artery were carried out, which could have a good angiographic
      pattern. His medical record shows that the patient has been suffering from
      persistent atrial fibrillation for a long time. There is also evidence for
      transient ischemic attacks in 2010 and 2011. The fact that there are no coronary
      artery stenoses after thrombus removal could suspect the thromboembolic genesis
      of myocardial infarction.

PMID- 25864364
TI  - [Clinical case of Jeune syndrome].
AB  - The paper reports a clinical case of Jeune syndrome in a baby, in whom the
      diagnosis was established immediately after his birth. He was also diagnosed as
      having multiple congenital malformations, such as Dandy-Walker anomaly,
      hexadactyly of the left hand, cleft palate, choroidal colobomas in both eyes, and
      atrial septal defect and he also had interstitial nephritis and hepatitis.

PMID- 25864365
TI  - [Diffusely growing brainstem tumors in children and adolescents: has alternating
      treatment policy changed results?].
AB  - The authors analyze the MEDLINE publications in the past 20 years on the
      treatment of diffusely growing brainstem tumors in children and adolescents.
      Radiation and chemoradiation are main treatments for these diseases. The use of
      different radiation dose fractionation modes and different combinations of
      cytotoxic drugs has caused no significant changes in long-term results. Whatever
      the used treatment option is, most patients die within the next 1-2 years after
      tumor progression. Prognosis mainly depends on the biological properties of a
      tumor and patients with low-grade glioma generally survive longer. The late
      effects of radiotherapy make quality of life worse in long-term survivors after
      treatment. Hopes to enhance therapeutic effectiveness are placed on the
      development of targeted therapy options based on molecular biological markers.

PMID- 25864366
TI  - [Intrahepatic cholangiocarcinoma].
AB  - The paper gives information on current approaches to diagnosing and treating
      intrahepatic cholangiocarcinoma (IHC), its microscopic and macroscopic varieties.
      It details the specific features of images of IHC by ultrasonography, X-ray
      computed tomography, magnetic resonance imaging (MRI), including those by
      diffusion-weighted MRI. Dynamic intravenous contrast enhancement and analysis of
      tumor hemodynamic features are emphasized to play a crucial role in different
      examination (arterial, venous, and delayed) phases. Diffuse heterogeneous
      enhancement of the whole volume of the tumor in the arterial phase with
      pronounced peripheral and progressing centripetal enhancement in ensuing phases
      is considered to be the most common type of an IHC image, which can recognize
      with confidence this comparatively rare neoplasm.

PMID- 25864367
TI  - Painful blister-free HSV-type 1 reactivation on the site of acute Lyme
      borreliosis.

PMID- 25864368
TI  - The reasons for insufficient enteral feeding in an intensive care unit: A
      prospective observational study.
AB  - BACKGROUND: Although enteral nutrition (EN) in critically ill patients is
      increasingly common, enteral underfeeding remains problematic. In the present
      study, we aimed to identify the reasons for insufficient EN. METHODS: In this
      single-centre, prospective, observational study in a general intensive care unit,
      the nurses documented cases experiencing enteral underfeeding during three-month
      study period. Decisions regarding EN were made and substantiated by the doctors.
      No feeding protocol was in use. The EN rate was assessed daily and considered
      insufficient if less than 50 kcal/h was administered and the rate had not
      increase in the previous 12 hour period. RESULTS: Eighty-seven patients were
      screened for 707 patient-days. Nurses documented 141 instances of insufficient EN
      in 49 patients (56.7% of all study subjects). EN was not initiated in 61% of
      these cases, EN was stopped in 14%, EN decreased in 2% and insufficient EN was
      not increased in 23%. EN was not initiated primarily due to surgical reasons. EN
      was not increased due to clinical instability. EN was decreased or stopped
      primarily due to high gastric residual volumes (GRV). The study served as step
      one in a quality improvement process and resulted in the introduction of a nurse
      driven feeding protocol. CONCLUSION: The main reasons for insufficient EN in
      intensive care patients include recent GI surgery, shock and large GRV. EN is
      commonly withheld for several days after GI surgery, whereas in shock there was a
      prohibition on increasing EN towards the target. Insufficient EN is highly
      prevalent; the incidence of EN should be reduced by training and the acceptance
      of more liberal EN policies.

PMID- 25864369
TI  - Interferon-free antiviral treatment of chronic hepatitis C in the transplant
      setting.
AB  - Interferon-based regimens with first-generation protease inhibitors have a
      limited efficacy and an unfavorable safety profile. Combination therapies with
      two or more second-generation direct-acting antivirals plus/minus ribavirin
      revolutionized treatment strategies in patients chronically infected with
      hepatitis C virus. In this rapidly evolving era, patients in the transplant
      setting benefit from interferon-free treatment regimens. Scientific societies can
      barely keep up with this development, making it necessary to update the clinical
      guidelines by the American and European Associations for the Study of Liver
      Diseases within short periods. This review presents and discusses the currently
      available data of the use of interferon-free treatment in the setting of liver
      transplantation. However, costs, different reimbursement strategies, and health
      care options cannot be answered by guidelines and recommendations from scientific
      societies. Further investigator-initiated trials are needed to individualize
      treatment concepts. 

PMID- 25864370
TI  - Magnesium and Dialysis: The Neglected Cation.
AB  - Disorders of magnesium homeostasis are very common in dialysis patients but have
      received scant attention. In this review, we address measurement of plasma
      magnesium, magnesium balance and the factors that affect magnesium flux during
      dialysis, the prevalence of hypo- and hypermagnesemia in dialysis patients, and
      the potential clinical significance of hypo- and hypermagnesemia in dialysis
      patients. Many factors can affect plasma magnesium concentration, including diet,
      nutritional status (including plasma albumin level), medications (such as proton
      pump inhibitors), and dialysis prescription. Further interventional studies to
      determine the effect of normalization of plasma magnesium concentration on
      clinical outcomes are needed. At the present time, we recommend that predialysis
      plasma magnesium be measured on a regular basis, with the dialysate magnesium
      concentration adjusted to maintain plasma magnesium concentration within the
      normal range. 

PMID- 25864371
TI  - Social anxiety and information processing biases: An integrated theoretical
      perspective.
AB  - Models of anxiety disorders posit that information processing biases towards
      threat may result from an imbalance between top-down attentional control
      processes and bottom-up attentional processes, such that anxiety could reduce the
      influence of the former and increase the influence of the latter. However,
      researchers have recently pointed to limitations of the top-down/bottom-up
      terminology and outlined the additional contribution of memory processes to
      attention guidance. The goal of this paper is to provide bridges between recent
      findings from cognitive psychology and anxiety disorders research. We first
      provide an integrative overview of the processes influencing the content of
      working memory, including the availability of attentional control, and the
      strengths of task goals, stimulus salience, selection history and long-term
      memory. We then illustrate the interest of this formulation to the study of
      information processing biases in anxiety disorders, with a specific focus on
      social anxiety. 

PMID- 25864372
TI  - Ecad vitiliGONE.

PMID- 25864373
TI  - Relationship between socioeconomic level, and the prevalence of masked
      hypertension and asymptomatic organ damage.
AB  - BACKGROUND: This study aimed to determine the prevalence of masked hypertension
      (MHT) and its association with asymptomatic organ damage (AOD) in a low
      socioeconomic district of Ankara, Turkey. MATERIAL AND METHODS: We
      retrospectively reviewed data obtained from the medical records of 712 patients
      with no known diagnosis of hypertension who presented to a polyclinic due to
      symptoms related to elevated blood pressure (BP) and were screened for MHT.
      Essential hypertension (EHT) existed in 86 patients screened for AOD. The
      presence of AOD in patients diagnosed with MHT and EHT was recorded. RESULTS:
      Among the 712 patients, 206 were diagnosed with EHT. Among the remaining 506
      patients, 73 were diagnosed with MHT. The patients with MHT had significantly
      higher left ventricular mass index, carotid intima-media thickness, and 24-h
      urinary microalbuminuria level (all indicators of AOD) than those with EHT.
      CONCLUSIONS: A significantly higher percentage of patients with MHT had AOD, as
      compared to those with EHT, in a low socioeconomic district of Ankara. Based on
      this finding, patients who present with hypertensive symptoms but have a normal
      BP should be advised to measure their BP at home.

PMID- 25864374
TI  - Knowledge, attitudes and beliefs towards waterpipe tobacco smoking and electronic
      shisha (e-shisha) among young adults in London: a qualitative analysis.
AB  - Introduction Waterpipe tobacco smoking (WTS), known in the United Kingdom as
      shisha, is popular among adolescents worldwide. Some electronic cigarettes are
      marketed in the United Kingdom as 'electronic shisha' (e-shisha). This study
      aimed to understand how WTS users view e-shisha and whether it could be used as a
      harm-reduction or cessation aid. METHOD: In-depth face-to-face interviews were
      conducted with 16 young adults recruited by snowball sampling in London, UK.
      Recurrent themes were derived iteratively through thematic analysis. RESULTS: WTS
      is a socially acceptable activity, carried out at home or in a cafe. Peer
      influence and flavour play a key role in its use. Participants were aware of some
      health risks of WTS, although many accepted this risk and reported a need for
      more health-related WTS information. Although participants were familiar with e
      shisha, there was no evidence of its use as a harm-reduction or cessation
      product. E-shisha tasted different to flavoured waterpipe tobacco and removed the
      positive social attributes typically ascribed to WTS. Waterpipe users felt e
      shisha may encourage non-users to initiate cigarettes or WTS. CONCLUSION:
      Opinions of reduced risk in using WTS may be due to the lack of available
      information, misconceptions and its easy accessibility. E-shisha does not appear
      to play a role in WTS harm reduction or cessation. On-going research efforts
      should test educational interventions addressing the adverse health impacts of
      WTS in this population group.

PMID- 25864375
TI  - Spatially confined catalysis-enhanced high-temperature carbon dioxide
      electrolysis.
AB  - In this study, a potential ilmenite cathode material Ni0.9TiO3 is designed for
      efficient CO2 electrolysis in an oxide-ion-conducting solid-oxide electrolyzer.
      Spatially confined catalysis has been successfully achieved to substantially
      improve cathode activity by in situ growth of catalytically active nickel
      nanoparticles on a ceramic skeleton. The combined analysis of XRD, SEM, EDS, XPS,
      TGA and Raman results together confirm that the growth of nickel catalyst is
      completely reversible in redox cycles. The n-type electrical properties of
      cathodes are systematically investigated and correlated to electrochemical
      performance. Efficient CO2 electrolysis with a Faraday efficiency above 90% has
      been demonstrated with Ni0.9TiO3 in contrast to 60% for a TiO2 cathode at 800 
      degrees C. 

PMID- 25864376
TI  - Molecular dynamics simulation for the reversed power stroke motion of a myosin
      subfragment-1.
AB  - Myosins are typical molecular motor proteins that convert the chemical energy
      from the ATP hydrolysis into mechanical work. The fundamental mechanism of this
      energy conversion is still unknown. To explain the experimental results already
      obtained, Masuda has proposed a hypothesis called the "Driven by Detachment"
      theory for the working principle of the myosins. This theory insists that the
      energy used during the power stroke of the myosins does not directly originate
      from the chemical energy of ATP, but is converted from the elastic energy within
      the molecule at the joint between the head and neck domains. One method for
      demonstrating the validity of this theory is a computational simulation using the
      molecular dynamics (MD) method. The MD software used was GROMACS. The target of
      the MD simulations was myosin subfragment-1 (S1), for which the initial structure
      was obtained from the Protein Data Bank entry 1M8Q. The AFM pull code of GROMACS
      was used to apply an external force of 17 pN at the end of the neck domain in the
      direction opposite to the power stroke to observe whether the myosin S1 takes the
      pre-power stroke conformation. The residues assumed to be engaged in the docking
      with an actin filament were fixed to the space. Starting from exactly the same
      initial position, 10 simulations were repeated by varying the random seeds for
      generating the initial velocities of the atoms. After 64ns of calculations, the
      myosin S1 took the conformation of the pre-power stroke state in which the neck
      domain was bent around the joint between the head and the neck domains. This
      result agrees with the prediction expected by the DbD theory, the validity of
      which may be established by conducting similar simulations for the other steps of
      the myosin working processes. 

PMID- 25864377
TI  - Qualitative, semi-quantitative, and quantitative simulation of the osmoregulation
      system in yeast.
AB  - In this paper we demonstrate how Morven, a computational framework which can
      perform qualitative, semi-quantitative, and quantitative simulation of dynamical
      systems using the same model formalism, is applied to study the osmotic stress
      response pathway in yeast. First the Morven framework itself is briefly
      introduced in terms of the model formalism employed and output format. We then
      built a qualitative model for the biophysical process of the osmoregulation in
      yeast, and a global qualitative-level picture was obtained through qualitative
      simulation of this model. Furthermore, we constructed a Morven model based on
      existing quantitative model of the osmoregulation system. This model was then
      simulated qualitatively, semi-quantitatively, and quantitatively. The obtained
      simulation results are presented with an analysis. Finally the future development
      of the Morven framework for modelling the dynamic biological systems is
      discussed. 

PMID- 25864378
TI  - Looking back and moving forward: recent advances in understanding of
      cardiovascular development by imaging of zebrafish.
AB  - Development requires cell proliferation, migration, differentiation, apoptosis,
      and many kinds of cell responses. Cells prepare intracellular conditions to
      respond to extracellular cues from neighboring cells. We have studied the
      development of the cardiovascular system (CVS) by visualizing morphology and
      signaling simultaneously using zebrafish, which express probes for both.
      Endodermal sheet is required for the bilateral cardiac precursor cell (CPC)
      migration toward the midline. Endothelial cells (ECs) proliferate specifically in
      the certain regions of blood vessels. Bone morphogenetic proteins (BMP) induce
      the remodeling of the caudal vein plexus (CVP) to form the caudal vein (CV). Our
      findings point to the pre-existing neighboring cells as the cells exhibiting
      certain responses during the development of CVS. In this review, we introduce
      recent results of our research on angiogenesis and cardiogenesis by spotlighting
      the mechanism by which ECs and CPCs are regulated by the cells next to
      themselves. In addition, we discuss the unanswered questions that should be
      clarified in the future in the field of CVS development. 

PMID- 25864380
TI  - What is the transfer mechanism of photogenerated carriers for the nanocomposite
      photocatalyst Ag3PO4/g-C3N4, band-band transfer or a direct Z-scheme?
AB  - The separation mechanisms of photoexcited carriers for composite photocatalysts
      are a hot point in the photocatalytic field. In this paper, the Ag3PO4/g-C3N4
      nanocomposites with different main parts (Ag3PO4 or g-C3N4) were synthesized
      using a facile in situ precipitation method. The photocatalysts were
      characterized by X-ray powder diffraction, UV-vis diffuse reflection
      spectroscopy, transmission electron microscopy and Brunauer-Emmett-Teller
      methods. The photocatalytic performance was evaluated by the degradation of
      methylene blue under visible light irradiation. When the main part of the
      Ag3PO4/g-C3N4 photocatalyst is Ag3PO4, the transfer mechanism of photogenerated
      electron-hole takes generic band-band transfer, and the photocatalytic activity
      is decreased. However, when the primary part of the Ag3PO4/g-C3N4 photocatalyst
      is g-C3N4, the migration of photogenerated electron-hole exhibits a typical Z
      scheme mechanism, and the photocatalytic activity is increased greatly. The
      separation mechanisms of photogenerated carriers were investigated by the
      electron spin resonance technology, the photoluminescence technique and the
      determination of reactive species in the photocatalytic reactions. It is hoped
      that this work could render guided information for design and application of Z
      scheme photocatalysts with excellent photocatalytic performance. 

PMID- 25864379
TI  - Bridging the Two Worlds: A Universal Interface between Enzymatic and DNA
      Computing Systems.
AB  - Molecular computing based on enzymes or nucleic acids has attracted a great deal
      of attention due to the perspectives of controlling living systems in the way we
      control electronic computers. Enzyme-based computational systems can respond to a
      great variety of small molecule inputs. They have the advantage of signal
      amplification and highly specific recognition. DNA computing systems are most
      often controlled by oligonucleotide inputs/outputs and are capable of
      sophisticated computing as well as controlling gene expressions. Here, we
      developed an interface that enables communication of otherwise incompatible
      nucleic-acid and enzyme-computational systems. The enzymatic system processes
      small molecules as inputs and produces NADH as an output. The NADH output
      triggers electrochemical release of an oligonucleotide, which is accepted by a
      DNA computational system as an input. This interface is universal because the
      enzymatic and DNA computing systems are independent of each other in composition
      and complexity. 

PMID- 25864381
TI  - Binge drinking during adolescence disrupts Se homeostasis and its main hepatic
      selenoprotein expression.
AB  - BACKGROUND: Binge drinking (BD) is the most common ethanol (EtOH) intake
      consumption model among teenagers, but little is known about its effects on the
      liver. During its hepatic metabolism, acute alcohol exposure produces a great
      amount of reactive oxygen species which contributes to alcohol-induced liver
      injury. Selenium (Se) plays a key role in antioxidant defense as it forms part of
      selenoproteins, such as the antioxidant glutathione peroxidases (GPxs) or the
      selenoprotein P (SelP), synthesized mainly in liver. Chronic EtOH consumption
      decreases both Se deposits and this tissue's antioxidant activity. METHODS: Two
      BD administration routes (oral and intraperitoneal) were used in adolescent rats
      to analyze Se homeostasis; the main hepatic selenoproteins' expression: GPx1,
      GPx4, and SelP, and their biological roles related to oxidation. Their
      relationship with inflammatory processes was also determined by analyzing the
      expression of the transcriptional factor nuclear factor-kappa beta (NF-kappaB).
      RESULTS: It has been demonstrated for the first time that BD in adolescents
      alters Se homeostasis regardless of the administration route employed, despite
      the fact that the BD oral group ingested less Se in diet. This decrease of Se in
      serum and liver is directly related to a decrease in serum GPx3 and hepatic GPx1
      activity, contributing to the oxidative imbalance found. The depletion of Se
      detected in liver affects GPx1 expression and, surprisingly, GPx4 expression.
      This could be related to the lower expression of the transcriptional factor NF
      kappaB in the liver, a key player in the regulation of inflammatory processes.
      CONCLUSIONS: Due to the above, and to find whether a Se supplementation therapy
      improves these situations, it would be interesting to explore in more depth the
      relationship between Se, the high oxidation found, and the depressed immune
      response reported in BD adolescents.

PMID- 25864382
TI  - Manipulation of persistent free radicals in biochar to activate persulfate for
      contaminant degradation.
AB  - This study investigated the effects of metals (Fe3+, Cu2+, Ni2+, and Zn2+) and
      phenolic compounds (PCs: hydroquinone, catechol, and phenol) loaded on biomass on
      the formation of persistent free radicals (PFRs) in biochar. It was found that
      metal and phenolic compound treatments not only increased the concentrations of
      PFRs in biochar but also changed the types of PFRs formed, which indicated that
      manipulating the amount of metals and PCs in biomass may be an efficient method
      to regulate PFRs in biochar. These results provided direct evidence to elucidate
      the mechanism of PFR formation in biochar. Furthermore, the catalytic ability of
      biochar toward persulfate activation for the degradation of contaminants was
      evaluated. The results indicated that biochar activates persulfate to produce
      sulfate radicals (SO4*-) and degraded polychlorinated biphenyls (PCBs)
      efficiently. It was found that both the concentration and type of PFRs were the
      dominant factors controlling the activation of persulfate by biochar and that
      superoxide radical anions account for 20-30% of sulfate radical generation in
      biochar/persulfate. This conclusion was supported by linear correlations between
      the concentration of PFRs consumed and the formation of SO4*- and between lambda
      (lambda=[formed sulfate radicals]/[consumed PFRs]) and g-factors. The findings of
      this study provide new methods to manipulate PFR concentration in biochar for the
      transformation of contaminants and development of new alternative activators for
      persulfate-based remediation of contaminated soils.

PMID- 25864383
TI  - Stimuli-responsive Pickering emulsions: recent advances and potential
      applications.
AB  - Pickering emulsions possess many advantages over traditional surfactant
      stabilized emulsions. For example, Pickering emulsions impart better stability
      against coalescence and, in many cases, are biologically compatible and
      environmentally friendly. These characteristics open the door for their use in a
      variety of industries spanning petroleum, food, biomedicine, pharmaceuticals, and
      cosmetics. Depending on the application, rapid, but controlled stabilization and
      destabilization of an emulsion may be necessary. As a result, Pickering emulsions
      with stimuli-responsive properties have, in recent years, received a considerable
      amounts of attention. This paper provides a concise and comprehensive review of
      Pickering emulsion systems that possess the ability to respond to an array of
      external triggers, including pH, temperature, CO2 concentration, light intensity,
      ionic strength, and magnetic field. Potential applications for which stimuli
      responsive Pickering emulsion systems would be of particular value, such as
      emulsion polymerization, enhanced oil recovery, catalyst recovery, and cosmetics,
      are discussed. 

PMID- 25864385
TI  - Perceptions of knowledge of disaster management among military and civilian
      nurses in Saudi Arabia.
AB  - BACKGROUND: It is generally accepted that nurses have insufficient knowledge
      about disaster preparedness due to a lack of acceptance of core competencies and
      the absence of disaster preparedness in nursing curricula. This study explored
      nurses' knowledge and sources of knowledge, and skills as they relate to disaster
      management in Saudi Arabia, where more than 4660 people have died, 32,000 people
      have been affected, and US$4.65 billion in damage has been caused by disaster
      since 1980. METHODS: A quantitative, non-experimental, descriptive research
      design. RESULTS: Nurses in Saudi Arabia have moderate knowledge concerning
      disaster preparedness. However, nurses in military hospitals possess more
      knowledge than those who work in government hospitals. The majority of nurses
      gained their knowledge and skills from disaster drills. CONCLUSIONS: Nurses need
      more education in all areas of disaster management, most importantly in their
      roles during response to disasters. Nurses perceive themselves as not well
      prepared but they are willing to improve their skills in disaster preparedness if
      educational opportunities are provided.

PMID- 25864384
TI  - CDK1 structures reveal conserved and unique features of the essential cell cycle
      CDK.
AB  - CDK1 is the only essential cell cycle CDK in human cells and is required for
      successful completion of M-phase. It is the founding member of the CDK family and
      is conserved across all eukaryotes. Here we report the crystal structures of
      complexes of CDK1-Cks1 and CDK1-cyclin B-Cks2. These structures confirm the
      conserved nature of the inactive monomeric CDK fold and its ability to be
      remodelled by cyclin binding. Relative to CDK2-cyclin A, CDK1-cyclin B is less
      thermally stable, has a smaller interfacial surface, is more susceptible to
      activation segment dephosphorylation and shows differences in the substrate
      sequence features that determine activity. Both CDK1 and CDK2 are potential
      cancer targets for which selective compounds are required. We also describe the
      first structure of CDK1 bound to a potent ATP-competitive inhibitor and identify
      aspects of CDK1 structure and plasticity that might be exploited to develop CDK1
      selective inhibitors. 

PMID- 25864386
TI  - The utility of MYC and FLT4 in the diagnosis and treatment of postradiation
      atypical vascular lesion and angiosarcoma of the breast.
AB  - Atypical vascular lesions (AVLs) and angiosarcomas (ASs) are well-recognized
      complications of radiotherapy for breast cancer. Early diagnosis may be
      challenging, particularly on small biopsies, and the treatment options are
      limited. Recently, MYC and sometimes FLT4 gene amplification has been reported in
      AS, but not in AVL, and FLT4 may be a target for therapy. We evaluated the
      MYC/FLT4 status in AVL and AS by immunohistochemistry (IHC) and fluorescence in
      situ hybridization (FISH), determined its utility in differentiating these 2
      entities in small biopsies, and ascertained the value of FLT4 as a potential
      marker for targeted therapy. Thirty-five vascular neoplasms were reviewed from 21
      breast cancer patients who received radiotherapy (AVL, n = 18; AS, n = 17). MYC
      expression by IHC and/or gene amplification by FISH were identified in 13 (77%)
      of 17 ASs, but none of the AVL cases. Four patients had biopsies with follow-up
      excisions, of which 1 showed the morphology of an AVL on biopsy and AS on
      excision, both positive for MYC. Of 17 ASs, 3 (18%) showed strong and diffuse 3+
      cytoplasmic FLT4 staining by IHC and FLT4 gene amplification by FISH. All 3 cases
      were coamplified for the MYC gene. Focal and weak FLT4 cytoplasmic
      immunoreactivity was present in 2 (12%) of 17 AVL cases and 12 (70%) of 17 AS
      cases. Although MYC is a valuable ancillary tool in distinguishing AS from AVL,
      FLT4 IHC may be used to screen for patients with FLT4 gene amplification who
      might benefit from targeted therapy, as only diffuse strong FLT4 immunoreactivity
      correlated with FLT4 gene amplification. 

PMID- 25864387
TI  - Developing cross-sectoral quality assurance for cataract surgery in the statutory
      quality assurance program of the German health care system: Experiences and
      lessons learned.
AB  - Since 2001, statutory external quality assurance (QA) for hospital care has been
      in place in the German health system. In 2009, the decision was taken to expand
      it to cross-sectoral procedures. This novel and unprecedented form of national QA
      aims at (1) making the quality procedures comparable that are provided both in
      inpatient and outpatient care, (2) following-up outcomes of hospital care after
      patients' discharge and (3) measuring the quality of complex treatment chains
      across interfaces. As a pioneer procedure a QA procedure in cataract surgery QA
      was developed. Using this as an example, challenges of cross-sectoral QA are
      highlighted. These challenges relate, in particular, to three technical problems:
      triggering cases for documentation, following-up patients' after hospital
      discharge, and the burden of documentation in outpatient care. These problems
      resulted finally in the haltering of the development of the QA procedure.
      However, the experiences gained with this first development of cross-sectoral QA
      inspired the reorientation and further development of the field in Germany.
      Future cross-sectoral QA will rigorously aim at keeping burden of documentation
      small. It will draw data for QA mainly at three sources: routine data, patient
      surveys and peer reviews using indicators. Policy implications of this
      reorientation are discussed. 

PMID- 25864388
TI  - Modeling the retention mechanism for high-performance liquid chromatography with
      a chiral ligand mobile phase and enantioseparation of mandelic acid derivatives.
AB  - The chromatographic retention mechanism describing relationship between retention
      factor and concentration of Cu(2+) (l-phenylalanine)2 using chiral ligand mobile
      phase was investigated and eight mandelic acid derivatives were enantioseparated
      by chiral ligand exchange chromatography. The relationship between retention
      factor and concentration of the Cu(2+) (l-phenylalanine)2 complex was proven to
      be in conformity with chromatographic retention mechanism in which chiral
      discrimination occurred both in mobile and stationary phase. Different copper(II)
      salts, chiral ligands, organic modifier, pH of aqueous phase, and conventional
      temperature on retention behavior were optimized. Eight racemates were
      successfully enantioseparated on a common reversed-phase column with an optimized
      mobile phase composed of 6 mmol/L of l-phenylalanine or N,N-dimethyl-l
      phenylalanine and 3 mmol/Lof copper(II) acetate or copper(II) sulfate aqueous
      solution and methanol. 

PMID- 25864389
TI  - The addition of nitriles to a molecular digermene: reversible addition and
      comparison to surface reactivity.
AB  - The addition of acetonitrile, propionitrile, and acrylonitrile to
      tetramesityldigermene was investigated and compared to the addition of
      acetonitrile and acrylonitrile to germanium dimers on the Ge(100)-2*1 surface. In
      each case, a 1,2,3-azadigermetine was formed as the major product. As on the
      surface, the addition of nitriles to digermenes was found to be reversible,
      providing the first example of a reversible cycloaddition of a ditetrelene. No
      evidence for a six-membered cyclic ketenimine was observed as noted in the
      surface chemistry, suggesting that the surface ketenimine might only form between
      two adjacent dimers rather than on a single dimer. The comparative chemistry
      provides important insights that are not possible by the independent study of
      each system. 

PMID- 25864390
TI  - Vitamin D analogue: potent antiproliferative effects on cancer cell lines and
      lack of hypercalcemic activity.
AB  - The active form of vitamin D3, 1alpha,25(OH)2D3, plays a major role in
      maintaining calcium/phosphate homeostasis. In addition, it is a potent
      antiproliferative and pro-differentiating agent. Unfortunately, it usually causes
      hypercalcemia in vivo when effective antitumour doses are used. It has therefore
      been found necessary to synthesise new analogues that retain or even increase the
      antitumour effects but preclude hypercalcemia. This report presents the synthesis
      of a novel Gemini vitamin D analogue (UVB1) and its biological evaluation. We
      demonstrate that this compound has potent antitumoural effects over a wide panel
      of tumour cell lines while showing lack of hypercalcemic activity and toxicity
      effects in in vivo assays.

PMID- 25864392
TI  - The role of pregnancy intention in HIV prevention in South Africa: a proposed
      model for policy and practice.
AB  - Mother-to-child transmission is a continuing source of new HIV infections in
      South Africa. The paper posits that insight into the socio-cultural, behavioural,
      environmental and economic factors that sustain the HIV epidemic is as important
      as understanding the biological causes of the disease when planning and
      implementing interventions to prevent and reduce perinatal transmission.
      Furthermore, understanding the pregnancy intentions of individuals in areas of
      endemic HIV/AIDS is vital for providing the best care for individuals who are HIV
      positive. This paper suggests a model for types of support and interventions that
      are relative to the intention of HIV-positive women or couples to become
      pregnant. Included among these are interventions for prevention of unwanted
      pregnancy, prevention of transmission of HIV, protection of the infant, and
      protection of the mother. 

PMID- 25864391
TI  - Structure of the yeast Bre1 RING domain.
AB  - Monoubiquitination of histone H2B at Lys123 in yeast plays a critical role in
      regulating transcription, mRNA export, DNA replication, and the DNA damage
      response. The RING E3 ligase, Bre1, catalyzes monoubiquitination of H2B in
      concert with the E2 ubiquitin-conjugating enzyme, Rad6. The crystal structure of
      a C-terminal fragment of Bre1 shows that the catalytic RING domain is preceded by
      an N-terminal helix that mediates coiled-coil interactions with a
      crystallographically related monomer. Homology modeling suggests that the human
      homologue of Bre1, RNF20/RNF40, heterodimerizes through similar coiled-coil
      interactions.

PMID- 25864393
TI  - Understanding diversity in impact and responses among HIV/AIDS-affected
      households: the case of Msinga, South Africa.
AB  - To gain a more comprehensive understanding of the impact of HIV and AIDS on rural
      households in Msinga, South Africa, the sustainable livelihoods framework was
      adapted. An ethnographic perspective was employed to examine: 1) the impact of
      HIV/AIDS-related illnesses on people's mind and spirit (the internal
      environment), and 2) the influence of institutional structures and processes (the
      external environment), in order to better understand 3) the actions taken by
      individuals and households in response to HIV and AIDS. Members of three support
      groups at a local drop-in centre were consulted about the impact of HIV and AIDS
      on their lives through focus groups, a questionnaire and in-depth interviews. The
      study shows that the psychosocial impact and associated coping strategies, as
      well as prevailing gender-based power relations and exclusion from social
      exchange networks - which are not (readily) available factors in the sustainable
      livelihoods framework - affect people's lives in different ways and depend on the
      specific situation of the individual or household concerned. The study confirms
      the need to restore a household's resource base and to address psychosocial
      issues. However, the variation in impact to different households requires a
      diversified and holistic programme of development interventions. 

PMID- 25864394
TI  - Migration, pastoralists, HIV infection and access to care: the nomadic Fulani of
      northern Nigeria.
AB  - The burden of HIV infection among the nomadic Fulani of northern Nigeria is
      unknown. Migration - a way of life for this population - is known to increase the
      rate of HIV transmission and may limit individuals' access to treatment and care.
      Many of Africa's other traditional, pastoral societies are similarly affected.
      This paper explores cultural practices and factors among the Fulani that may
      influence HIV transmission, vulnerability to infection, sustainability and
      challenges to treatment access, and avenues and models for outreach services;
      lastly, we proffer some solutions and recommendations. An extensive literature
      search with cross-referencing was done, and relevant publications on similar
      themes were reviewed. Three cases of Fulani nomads with HIV are presented to
      illustrate the challenge of providing a care continuum as well as to demonstrate
      successes when appropriate HIV interventions are employed. Patient interviews
      provide valuable insight and information on living and coping with HIV. Community
      mobility limits opportunities for counselling, testing and diagnosis, as well as
      HIV-related care access and maintenance. Consanguinity and certain cultural
      practices among the Fulani have clear amplification potential for HIV
      transmission. Treatment support through the use of coaches and life partners
      improves adherence to antiretroviral therapy (ART). Existing programmes for
      nomads afford opportunities for absorption and integration of HIV services.
      Nomadic communities should be provided with basic HIV-related services, including
      risk-reduction education and methods, counselling and testing, ART, medication
      adherence counselling, access to laboratory tests and health monitoring. These
      services should be taken to nomadic communities using novel approaches such as
      mobile units, extension services, case management, directly observed care, and
      treatment supporters linked to neighbouring health facilities in a hub-and-spoke
      model. Stronger collaborations are recommended between programmes for nomads and
      HIV services, and also between veterinary and public health services. Community
      participation and leadership should be encouraged to ensure the sustainability of
      HIV-related care delivery. More research is needed on the epidemiology and
      sociology of HIV infection and the best ways to provide services to hard-to-reach
      nomadic populations. 

PMID- 25864395
TI  - Clinical waste management in the context of the Kanye community home-based care
      programme, Botswana.
AB  - This study examines clinical waste disposal and handling in the context of a
      community home-based care (CHBC) programme in Kanye, southern Botswana. This
      qualitative study involved 10 focus group discussions with a total of 82 HIV/AIDS
      primary caregivers in Kanye, one-to-one interviews with the five nurses
      supervising the programme, and participant observation. Numerous aspects of
      clinical or healthcare waste management were found to be hazardous and
      challenging to the home-based caregivers in the Kanye CHBC programme, namely:
      lack of any clear policies for clinical waste management; unhygienic waste
      handling and disposal by home-based caregivers, including burning and burying the
      healthcare wastes, and the absence of pre-treatment methods; inadequate
      transportation facilities to ferry the waste to clinics and then to appropriate
      disposal sites; stigma and discrimination associated with the physical removal of
      clinical waste from homes or clinics; poor storage of the healthcare waste at
      clinics; lack of incinerators for burning clinical waste; and a high risk of
      contagion to individuals and the environment at all stages of managing the
      clinical waste. 

PMID- 25864396
TI  - Representations of HIV/AIDS management in South African newspapers.
AB  - In South Africa, numerous strong policy statements emphasise the importance of
      involving communities in HIV/AIDS management, yet in practice such involvement
      tends to be tokenistic and minimal. Social representations in the public sphere
      constitute the symbolic dimension within which responses to HIV and AIDS are
      conceptualised and transformed into action. Through an analysis of newspaper
      articles, we explore the dominant representations of HIV/AIDS management
      circulating in the South African public sphere and examine how community
      engagement is depicted. We highlight the way media representations reflect narrow
      understandings of HIV and AIDS as a predominantly medical problem, while
      depicting HIV/AIDS management as a top-down activity dominated by prominent
      individuals, such as national leaders, health professionals and philanthropists,
      thus marginalising the role played by communities, who are often depicted as
      passive recipients of interventions by active outsiders. These representations
      fail to reflect the key role played by members of grassroots communities in
      responding to the HIV epidemic. Such representations provide flawed conceptual
      tools for shaping responses to the epidemic, given that HIV-related programmes
      are unlikely to have optimal outcomes unless they resonate with the perceived
      needs and interests of their target communities, as we contend that effective
      HIV/AIDS management is best achieved through active participation by communities
      in HIV/AIDS management strategies. We discuss the implications of a more 'civic
      minded journalism.' 

PMID- 25864397
TI  - Health-related quality of life in a sample of HIV-infected South Africans.
AB  - The study aims to assess the health-related quality of life and HIV symptoms of a
      sample of people living with HIV (PLHIV) in South Africa. The sample included 607
      PLHIV from all districts of the Eastern Cape Province, recruited either through a
      health facility, from the community through key informants, or through support
      groups. At the time of the study, 66% of the respondents reported having been
      given an AIDS diagnosis (advanced stage of HIV disease), 48% were on
      antiretroviral therapy (ART), and 35% were receiving a disability grant. The
      findings indicate a low degree of overall quality of life, with a mean score of
      13.4 on the WHOQOL-HIV measure. Among the WHOQOL-HIV BREF subscales, logistic
      regression identified spirituality, environment, psychological health, and level
      of independence as predictors for overall quality of life. Among medical
      variables and HIV symptoms, CD4 cell count and having fewer HIV symptoms but not
      an AIDS diagnosis were identified as predictors for overall quality of life;
      among socio-economic variables, having sufficient food and a higher educational
      level were identified as predictors. The results highlight the need for better
      access to psychosocial support and medical services for PLHIV in South Africa, as
      well as the need to consider a patient's general health perceptions during the
      course of ART. 

PMID- 25864398
TI  - Community approaches to preventing mother-to-child HIV transmission: perspectives
      from rural Lesotho.
AB  - This paper examines the cultural and structural difficulties surrounding
      effective prevention of mother-to-child HIV transmission (PMTCT) in rural
      Lesotho. We argue for three strategies to improve PMTCT interventions: community
      based research and outreach, addressing cultural and structural dynamics, and
      working with the relevant social groups that impact HIV prevention. These
      conclusions are based on interviews and participant observation conducted within
      the rural Mokhotlong district and capital city of Maseru, involving women and men
      of reproductive age, grandmothers serving as primary caretakers, HIV/AIDS
      programme staff, and medical professionals. Qualitative analysis focused on rural
      women's socio-medical experience with the four measures of PMTCT (educational
      outreach, voluntary counselling and testing, antiretroviral interventions, and
      safe infant feeding). Based on these results, we conclude that intervention
      models must move beyond a myopic biomedical 'best-practices' approach to address
      the social groups and contextual determinants impacting vertical HIV
      transmission. Given the complexities of effective PMTCT, our results show that it
      is necessary to consider the biomedical system, women and children, and the
      community as valuable partners in achieving positive health outcomes. 

PMID- 25864399
TI  - High prevalence of HIV and malaria co-infection in urban Douala, Cameroon.
AB  - A prospective cohort study was undertaken among 684 adult hospital attendees in
      Douala, Littoral Province, Cameroon. The objectives were to determine the
      prevalence of HIV/malaria co-infection and to determine and compare the
      prevalence of some parasitological, haematological and clinical parameters
      between co-infection and mono-infection with HIV or malaria in the study
      population. Information was collected on HIV serostatus, and malaria parasitaemia
      was assessed from blood smears by microscopy. Haemoglobin concentration was
      measured using the STANBIO STAT-Site MHgb Test System((r)), and CD4 cell counts
      were obtained using the Partec CyFlow Counter((r)). The prevalence of HIV/malaria
      co-infection in the sample was 29.4%. Geometric mean parasitaemia was
      significantly higher in co-infected patients than in malaria patients (9 868
      parasites/MUL blood versus 6 134 parasites/MUL blood; F = 3.44, p = 0.018).
      Anaemia was more prevalent in cases of co-infection (43.3%) than in cases of HIV
      mono-infection (36.8%) or malaria mono-infection (20.4%) (chi(2) = 12.38, p =
      0.006). The mean CD4 cell count between the groups of co-infected and HIV-mono
      infected patients was not significantly different (F = 0.004, p = 1.000), but
      more patients with dual infections had CD4 cell counts corresponding to the
      chronic and advanced stages of HIV infection. A total of 105 individuals were
      successfully followed up for six months; twelve deaths were recorded within this
      period, nine of which were co-infected patients. Our results add to the existing
      pool of data from similar studies showing that HIV/malaria co-infections have a
      significant effect on a patient's clinical outcome. The data provide a basis for
      more elaborate studies with a larger sample size and follow-up of longer duration
      in the study region. 

PMID- 25864400
TI  - Habitual physical activity levels are positively correlated with CD4 counts in an
      HIV-positive South African population.
AB  - In order to assess the relationship between CD4 cell count, habitual physical
      activity levels and functional independence in a South African adult population
      positive for HIV, we administered a questionnaire concerning lifestyle and
      physical activity. Data collection took place at an antiretroviral (ARV) roll-out
      site at Helen Joseph Hospital, Johannesburg. The study involved 186 HIV-positive
      outpatients (47 male and 139 female), with a mean age of 35.2 years, who were
      either taking (n = 121) or not taking (n = 65) ARV medication. We compared CD4
      cell count, habitual physical activity levels (metabolic intensity in MET hours
      per month) and functional independence as assessed from the responses to the
      questionnaire. There was a positive and significant correlation between the
      patients' length of time on ARV medication and CD4 cell counts (p < 0.0001, r =
      0.45), and between CD4 cell counts and total habitual physical activity levels (p
      = 0.0067, r = 0.20). Patients considering themselves functionally independent
      also had significantly higher CD4 cell counts (p = 0.0031). The use of ARV
      medication, despite the related side-effects, was associated with a higher CD4
      cell count, which in this population was also associated with increased habitual
      physical activity levels and a greater sense of functional independence. 

PMID- 25864401
TI  - HIV pre-exposure prophylaxis trials: socio-economic and ethical perspectives for
      sub-Saharan Africa.
AB  - The advent of HIV pre-exposure prophylaxis (PrEP) as a HIV-prevention strategy
      has received optimistic support among HIV researchers. However, discourse on PrEP
      trials has tended to be dominated by the disputes arising between some activist
      groups and researchers about the research methodologies. Instead, this paper
      discusses other issues oftentimes neglected in discussions relating to PrEP
      trials. Specifically, I focus on the possible ethical implications and the
      potential impact of sub-Saharan Africa's socio-economic conditions on the
      promised benefits of PrEP trials for the region and the continent. I argue that
      the concept of PrEP as a affordable and practical HIV-prevention intervention
      presents challenges and questions that urgently need addressing as we await
      results from several ongoing trials. If research is undertaken with no plans on
      how the results of specific trials can render actual HIV-prevention-benefits -
      especially for the world's poor - then such endeavours risk being merely
      information-acquiring ventures. 

PMID- 25864402
TI  - Effect of Irrigant Characteristics on Lesion Formation After Radiofrequency
      Energy Delivery Using Ablation Catheters with Actively Cooled Tips.
AB  - BACKGROUND: The delivery of radiofrequency (RF) energy through irrigated ablation
      catheters may be affected by irrigant osmolarity and by catheter position. We
      sought to characterize lesion formation characteristics using different irrigants
      in both open and closed irrigated catheter. METHODS: An ex vivo model consisting
      of viable bovine myocardium and a submersible load cell was assembled in a
      circulating saline bath at 37 degrees C. An externally irrigated ablation
      catheter and a closed irrigated catheter were positioned with 10 g of force in
      both perpendicular and parallel positions. A series of ablation lesions using
      different irrigants were delivered using a constant rate of irrigation (30
      cc/min) at 50 W. Potential clinical applicability was evaluated in vivo by
      targeting porcine epicardium with different irrigants during open irrigation
      ablation and assessing lesion sizes. RESULTS: Ablation in the perpendicular
      position produced significantly larger lesions for all irrigants, compared to
      their respective parallel position ablation. For both open and closed irrigated
      ablation, half normal saline (HNS) ablation created larger lesions than normal
      saline (NS), and dextrose water (D5W) lesions were significantly larger than both
      HNS and NS lesions. Steam pops were mostly observed in the perpendicular
      position, and the rate of steam pops was statistically higher only for open
      irrigated D5W, but not for HNS, when compared to NS. Both open and closed
      irrigated ablation with D5W and HNS in the parallel position created larger
      lesions than parallel NS ablation without causing more steam pops. In an in vivo
      porcine model, open irrigated ablation with D5W created larger lesions compared
      to standard NS irrigation. CONCLUSIONS: In ex vivo and in vivo models, decreased
      osmolarity and charge density increased RF energy delivery to tissue, resulting
      in larger lesions for both open and closed irrigated ablations. A perpendicular
      catheter position created larger lesions across all irrigants for both open and
      closed irrigation ablation. The incidence of steam pops was observed more
      frequently with high power open irrigated using D5W, especially if the catheter
      was in a perpendicular position. Further research is required to evaluate any
      clinical role for using different irrigants with an externally irrigated
      catheter.

PMID- 25864404
TI  - Neutrophil apoptosis in the context of tuberculosis infection.
AB  - Polymorphonuclear neutrophils comprise two-thirds of peripheral blood leukocytes
      and are key components of innate immunity as a first line of defense against
      bacterial and fungal pathogens. Their microbicidal mechanisms are essential for
      bacterial killing, the enhancement of inflammatory reactions and also comprise
      signaling molecules which have been implicated in signal transduction cascades.
      In tuberculosis, the number of neutrophils increases in the affected lung. In
      addition, they become activated and apoptotic due the bacterial burden. As
      apoptosis is promoted by reactive oxygen species (ROS) during phagocytosis, the
      advantages and benefits to the host as well as the strategies displayed by the
      pathogen to avoid or retard apoptosis are discussed in this review. 

PMID- 25864403
TI  - Conceptual Integration of Arithmetic Operations With Real-World Knowledge:
      Evidence From Event-Related Potentials.
AB  - Research on language processing has shown that the disruption of conceptual
      integration gives rise to specific patterns of event-related brain potentials
      (ERPs)-N400 and P600 effects. Here, we report similar ERP effects when adults
      performed cross-domain conceptual integration of analogous semantic and
      mathematical relations. In a problem-solving task, when participants generated
      labeled answers to semantically aligned and misaligned arithmetic problems (e.g.,
      6 roses + 2 tulips = ? vs. 6 roses + 2 vases = ?), the second object label in
      misaligned problems yielded an N400 effect for addition (but not division)
      problems. In a verification task, when participants judged arithmetically correct
      but semantically misaligned problem sentences to be "unacceptable," the second
      object label in misaligned sentences elicited a P600 effect. Thus, depending on
      task constraints, misaligned problems can show either of two ERP signatures of
      conceptual disruption. These results show that well-educated adults can integrate
      mathematical and semantic relations on the rapid timescale of within-domain ERP
      effects by a process akin to analogical mapping. 

PMID- 25864405
TI  - Viscoelastic blood coagulation measurement with Sonoclot predicts postoperative
      bleeding in cardiac surgery after heparin reversal.
AB  - OBJECTIVES: The aim of the study was to determine if Sonoclot with its sensitive
      glass bead-activated, viscoelastic test can predict postoperative bleeding in
      patients undergoing cardiac surgery at predefined time points. DESIGN: A
      prospective, observational clinical study. SETTING: A teaching hospital, single
      center. PARTICIPANTS: Consecutive patients undergoing cardiac surgery (N = 300).
      INTERVENTIONS: Besides routine laboratory coagulation studies and heparin
      management with standard (kaolin) activated clotting time, additional native
      blood samples were analyzed on a Sonoclot using glass bead-activated tests. Glass
      bead-activated clotting time, clot rate, and platelet function were recorded
      immediately before anesthesia induction and at the end of surgery after heparin
      reversal but before chest closure. MEASUREMENTS AND MAIN RESULTS: Primary outcome
      was postoperative blood loss (chest tube drainage at 4, 8, and 12 hours
      postoperatively). Secondary outcome parameters were transfusion requirements,
      need for surgical re-exploration, time of mechanical ventilation, length of
      intensive care unit and hospital stay, and hospital morbidity and mortality.
      Patients were categorized into "bleeders" and "nonbleeders." Patient
      characteristics, operations, preoperative standard laboratory parameters, and
      procedural times were comparable between bleeders and nonbleeders except for sex
      and age. Bleeders had higher rates of transfusions, surgical re-explorations, and
      complications. Only glass bead measurements by Sonoclot after heparin reversal
      before chest closure but not preoperatively were predictive for increased
      postoperative bleeding. CONCLUSIONS: Sonoclot with its glass bead-activated tests
      may predict the risk for postoperative bleeding in patients undergoing cardiac
      surgery at the end of surgery after heparin reversal but before chest closure.

PMID- 25864406
TI  - Factors predictive of improved overall survival following stereotactic
      radiosurgery for recurrent glioblastoma.
AB  - The currently accepted standard of care for primary glioblastoma (GBM) consists
      of maximal surgical resection followed by fractionated external beam radiotherapy
      (EBRT) with concomitant temozolomide chemotherapy. The role of stereotactic
      radiosurgery (SRS) in the treatment of GBM is not well defined, but SRS has
      typically been applied as a salvage therapy for GBM recurrence. This paper
      reviews our single institution experience using gamma knife radiosurgery (GKRS)
      for the treatment of GBM. Thirty-six patients treated with GKRS for
      pathologically proven GBM at LSU Health in Shreveport from February 2000 to
      December 2013 were identified and analyzed. Patient characteristics, treatment
      variables, and survival were correlated. Seven patients received GKRS in the
      immediate postoperative period for an average tumor volume of 10.9 cm(3), and 29
      patients were treated for a recurrent average tumor volume of 11.4 cm(3) with a
      prescribed dose ranging from 10 to 20 Gy at the 50 % isodose line. The median
      overall survival was significantly higher in recurrence group compared to up
      front group [7.9 months (0.77-32.1 months) vs. 3.5 months (range 0.23-11.7
      months) respectively, (p = 0.018)]. The predictive factors for improved survival
      in the patients with GBM were as follows: Karnofsky performance scale (KPS) > 70
      (p = 0.026), age <= 50 years (p = 0.006), absence of neurodeficits (p = 0.01),
      and initial postoperative treatment with EBRT (p = 0.042). Adjuvant therapy with
      GKRS following GBM recurrence demonstrates statistical superiority over immediate
      postoperative boost therapy. 

PMID- 25864408
TI  - Categorization of cancer through genomic complexity could guide research and
      management strategies.
AB  - Cancer management decisions are currently informed by cancer type and clinical
      stage, as well as age, health condition, and individual patient needs. Cancer is
      a genetic disease and recent genomic studies have revealed the genomic landscape
      of multiple tumour types. This has led to readily available catalogues of genomic
      features for many cancers and efforts to incorporate such information into
      treatment decisions. From this has evolved the concept that mutation-based
      taxonomies may supersede the current cell of origin-based categorization of
      neoplasia. Unfortunately, genomic features as clinically actionable information
      may not be directly transferable between tumour types, due to the importance of
      cellular and genomic context. However, we believe that high-level views of
      different genomic landscapes could broadly inform research study design and
      treatment strategies. Herein, we use ovarian and bone cancer as examples to
      propose a genomic complexity-based categorization for cancer. In addition to
      informing clinical study design, we describe how this categorization scheme could
      impact (i) improvement of accuracy of histological diagnoses, (ii) stratification
      of patients for targeted therapies, (iii) research study design, and (iv)
      personalized treatment strategies.

PMID- 25864407
TI  - Association between paracetamol use in infancy or childhood with body mass index.
AB  - OBJECTIVE: Paracetamol has the potential to also promote weight gain by indirect
      activation of cannabinoid receptors. The association between paracetamol use in
      the first 12 months of life or recent high use and BMI in children and
      adolescents was investigated. METHODS: Paracetamol use in the first 12 months of
      life (reported by parents/guardians of 6- and 7-year-olds) or in the past 12
      months (reported by parents/guardians of 6- and 7-year-olds or self-reported by
      adolescents aged 13-14) was examined in relation to BMI in a large multicentre
      cross-sectional study (2000-2003). Linear regression results were adjusted for
      whether height and weight were reported or measured, age, sex, country gross
      national income, study centre, maternal smoking, and recent wheeze. RESULTS: Data
      were available from 76,216 children (18 countries) and 188,469 adolescents (35
      countries). BMI was +0.07 kg/m2 higher in children with early life paracetamol
      exposure, from affluent countries only. Frequent recent paracetamol use was
      associated with higher BMI (+0.17 kg/m2, P < 0.0001) among adolescents from
      affluent countries only, but not in children (P = 0.41). CONCLUSIONS: Paracetamol
      may be causally related to increased BMI; alternatively, the association may be
      explained by lifestyle or other factors that correlate with paracetamol use in
      affluent countries.

PMID- 25864409
TI  - In situ synthesis of a large area boron nitride/graphene monolayer/boron nitride
      film by chemical vapor deposition.
AB  - We describe the successful in situ chemical vapor deposition synthesis of a
      graphene-based heterostructure in which a graphene monolayer is protected by top
      and bottom boron nitride films. The boron nitride film/graphene monolayer/boron
      nitride film (BGB) was found to be a mechanically robust and chemically inert
      heterostructure, from which the deleterious effects of mechanical transfer
      processes and unwanted chemical doping under air exposure were eliminated. The
      chemical compositions of each film layer were monitored ex situ using UV-visible
      absorption spectroscopy and X-ray photoelectron spectroscopy, and the crystalline
      structures were confirmed using transmission electron microscopy and selected
      area electron diffraction measurements. The performance of the devices fabricated
      using the BGB film was monitored over six months and did not display large
      changes in the mobility or the Dirac point, unlike the conventional graphene
      devices prepared on a SiO2 substrate. The in situ-grown BGB film properties
      suggest a novel approach to the fabrication of commercial-grade graphene-based
      electronic devices. 

PMID- 25864410
TI  - Rape-related cognitive distortions: Preliminary findings on the role of early
      maladaptive schemas.
AB  - Despite the important focus on the notion of cognitive distortions in the sexual
      offending area, the relevance of underlying cognitive schemas in sexual offenders
      has also been suggested. The aim of the present study was to investigate a
      potential relationship between Early Maladaptive Schemas (EMSs) and cognitive
      distortions in rapists. A total of 33 men convicted for rape completed the Bumby
      Rape Scale (BRS), the Young Schema Questionnaire - Short form-3 (YSQ-S3), the
      Brief Symptom Inventory (BSI), and the Socially Desirable Response Set Measure
      (SDRS-5). Results showed a significant relationship between the impaired limits
      schematic domain and the Justifying Rape dimension of the BRS. Specifically,
      after controlling for psychological distress levels and social desirability
      tendency, the entitlement/grandiosity schema from the impaired limits domain was
      a significant predictor of cognitive distortions related to Justifying Rape
      themes. Overall, despite preliminary, there is some evidence that the Young's
      Schema-Focused model namely the impaired limits dimension may contribute for the
      conceptualization of cognitive distortions in rapists and further investigation
      is recommended. 

PMID- 25864411
TI  - Conformal, macroscopic crystalline nanoparticle sheets assembled with DNA.
AB  - A novel method for preparing conformal silica-embedded crystalline nanoparticle
      sheets via DNA programmable assembly provides independent control over
      nanoparticle size, nanoparticle spacing, and film thickness. The conformal
      materials retain the nanoparticle crystallinity and spacing after being
      transferred to flat or highly curved substrates even after being subjected to
      various mechanical, physical, and chemical stimuli. 

PMID- 25864412
TI  - The single fgf receptor gene in the beetle Tribolium castaneum codes for two
      isoforms that integrate FGF8- and Branchless-dependent signals.
AB  - The precise regulation of cell-cell communication by numerous signal-transduction
      pathways is fundamental for many different processes during embryonic
      development. One important signalling pathway is the evolutionary conserved
      fibroblast-growth-factor (FGF)-pathway that controls processes like cell
      migration, axis specification and mesoderm formation in vertebrate and
      invertebrate animals. In the model insect Drosophila, the FGF ligand / receptor
      combinations of FGF8 (Pyramus and Thisbe) / Heartless (Htl) and Branchless (Bnl)
      / Breathless (Btl) are required for the migration of mesodermal cells and for the
      formation of the tracheal network respectively with both the receptors
      functioning independently of each other. However, only a single fgf-receptor gene
      (Tc-fgfr) has been identified in the genome of the beetle Tribolium. We therefore
      asked whether both the ligands Fgf8 and Bnl could transduce their signal through
      a common FGF-receptor in Tribolium. Indeed, we found that the function of the
      single Tc-fgfr gene is essential for mesoderm differentiation as well as for the
      formation of the tracheal network during early development. Ligand specific RNAi
      for Tc-fgf8 and Tc-bnl resulted in two distinct non-overlapping phenotypes of
      impaired mesoderm differentiation and abnormal formation of the tracheal network
      in Tc-fgf8- and Tc-bnl(RNAi) embryos respectively. We further show that the
      single Tc-fgfr gene encodes at least two different receptor isoforms that are
      generated through alternative splicing. We in addition demonstrate through exon
      specific RNAi their distinct tissue-specific functions. Finally, we discuss the
      structure of the fgf-receptor gene from an evolutionary perspective. 

PMID- 25864413
TI  - Validation of a Brief Dietary Assessment Tool for Estimating Dietary EPA and DHA
      Intake in Australian Adults at Risk of Cardiovascular Disease.
AB  - BACKGROUND: Short food frequency questionnaires (FFQs) are powerful screening
      instruments for estimating nutrient intakes and play an important role in risk
      stratification in vulnerable populations. Omega-3 fatty acids are of increasing
      importance in the prevention of chronic and degenerative disease, especially in
      older adults who are at higher risk of these chronic conditions. A short FFQ
      exists to rapidly assess omega-3 intake from marine sources, however it has not
      previously been validated for agreement with total omega-3 intake and ability to
      identify suboptimal omega-3 intakes in older adults or for use in Australia.
      OBJECTIVE: The aim of the study was to validate a 9-item marine omega-3 FFQ (MFQ)
      for assessment of omega-3 intake against a validated 74-item semiquantitative
      FFQ. METHODS: One hundred and eight participants (mean age 67 +/- 10 years, 47%
      male) completed the MFQ designed to estimate omega-3 intake from marine sources
      and the 74-item FFQ designed to estimate usual omega-3 and total energy intake in
      addition to other nutrients. To test agreement between the two questionnaires for
      estimating total omega-3 intake, mean bias and 95% limits of agreement (LOA) were
      calculated. Sensitivity and specificity were assessed using 2 * 2 contingency
      tables based on whether participants did or did not meet National Heart
      Foundation (NHF) recommendations for omega-3 intake per day. RESULTS: Mean intake
      of omega-3 estimated from the MFQ was 210 +/- 235 mg/day compared with 295 +/-
      260 mg/day as estimated by the FFQ. Mean bias (95% LOA) for omega-3 assessed by
      the two questionnaires was 89 mg/day (-475 mg to 653 mg). The MFQ achieved 98%
      sensitivity and 31% specificity for the omega-3 cut-off of 500 mg/day. When
      nutrient composition of the marine products were replaced with Australian data,
      mean intake of omega-3 was 230 +/- 253 mg and the mean bias improved to 64 mg (
      681 mg to 553 mg) and achieved 93% sensitivity and 40% specificity. CONCLUSIONS:
      The MFQ shows promise as a rapid screening tool for identifying older adults with
      intakes of omega-3 fatty acids likely to be below recommendations for chronic and
      degenerative disease risk reduction. Given the clinically meaningful mean bias
      and wide LOA, it cannot be recommended as an appropriate tool for the purpose of
      reporting average intake of individuals. Use of Australian nutrient data improved
      the mean bias of the tool in estimating total omega-3 intake. The values should
      be replaced and the MFQ could then be a useful tool for research purposes at the
      population level.

PMID- 25864414
TI  - Karyotype evolution in apomictic Boechera and the origin of the aberrant
      chromosomes.
AB  - Chromosome rearrangements may result in both decrease and increase of chromosome
      numbers. Here we have used comparative chromosome painting (CCP) to reconstruct
      the pathways of descending and ascending dysploidy in the genus Boechera (tribe
      Boechereae, Brassicaceae). We describe the origin and structure of three Boechera
      genomes and establish the origin of the previously described aberrant Het and Del
      chromosomes found in Boechera apomicts with euploid (2n = 14) and aneuploid (2n =
      15) chromosome number. CCP analysis allowed us to reconstruct the origin of seven
      chromosomes in sexual B. stricta and apomictic B. divaricarpa from the ancestral
      karyotype (n = 8) of Brassicaceae lineage I. Whereas three chromosomes (BS4, BS6,
      and BS7) retained their ancestral structure, five chromosomes were reshuffled by
      reciprocal translocations to form chromosomes BS1-BS3 and BS5. The reduction of
      the chromosome number (from x = 8 to x = 7) was accomplished through the
      inactivation of a paleocentromere on chromosome BS5. In apomictic 2n = 14 plants,
      CCP identifies the largely heterochromatic chromosome (Het) being one of the BS1
      homologues with the expansion of pericentromeric heterochromatin. In apomictic B.
      polyantha (2n = 15), the Het has undergone a centric fission resulting in two
      smaller chromosomes - the submetacentric Het' and telocentric Del. Here we show
      that new chromosomes can be formed by a centric fission and can be fixed in
      populations due to the apomictic mode of reproduction.

PMID- 25864415
TI  - Structure-activity relationship (SAR) modelling of mosquito larvicides.
AB  - An attempt was made to derive structure-activity models allowing the prediction
      of the larvicidal activity of structurally diverse chemicals against mosquitoes.
      A database of 188 chemicals with their activity on Aedes aegypti larvae was
      constituted from analysis of original publications. The activity values were
      expressed in log 1/IC50 (concentration required to produce 50% inhibition of
      larval development, mmol). All the chemicals were encoded by means of CODESSA and
      autocorrelation descriptors. Partial least squares analysis, classification and
      regression tree, random forest and boosting regression tree analyses, Kohonen
      self-organizing maps, linear artificial neural networks, three-layer perceptrons,
      radial basis function artificial neural networks and support vector machines with
      linear, polynomial, radial basis function and sigmoid kernels were tested as
      statistical tools. Because quantitative models did not give good results, a two
      class model was designed. The three-layer perceptron significantly outperformed
      the other statistical approaches regardless of the threshold value used to split
      the data into active and inactive compounds. The most interesting configuration
      included eight autocorrelation descriptors as input neurons and four neurons in
      the hidden layer. This led to more than 96% of good predictions on both the
      training set and external test set of 88 and 100 chemicals, respectively. From
      the overall simulation results, new candidate molecules were proposed which will
      be shortly synthesized and tested. 

PMID- 25864416
TI  - Comparing the treatment outcomes of potassium-titanyl-phosphate laser
      vaporization and transurethral electroresection for primary nonmuscle-invasive
      bladder cancer: A prospective, randomized study.
AB  - BACKGROUND AND OBJECTIVES: In urology, potassium-titanyl-phosphate (KTP) laser is
      mainly used in the treatment of benign prostatic hyperplasia with a low rate of
      intraoperative and postoperative complications. A prospective, randomized study
      was undertaken to investigate the treatment outcomes of KTP laser vaporization
      for primary non-muscle-invasive bladder tumors (NMIBTs) as compared with
      conventional monopolar transurethral resection of bladder tumors (TURBT).
      MATERIALS AND METHODS: This study was designed as a prospective, randomized
      trial. After institutional review board approval, 229 consecutive patients with
      NMIBTs were randomized to 2 groups. Among them, 116 patients underwent KTP laser
      vaporization of a bladder tumor (laser group) and 113 patients underwent standard
      transurethral electroresection of the bladder tumors using monopolar loop
      electrode (TURBT group). According to the prognostic factors for recurrence, all
      patients were divided into low, intermediate or high risk subgroups. The clinical
      data were recorded and compared between the two groups. RESULTS: Eighty-nine
      patients in laser group and 94 in TURBT group were evaluable for the study end
      points. The preoperative characteristics of the patients were comparable in the
      two groups. There was no statistical difference in operation time between the two
      groups. Patients in the laser group had fewer perioperative complications and
      more patients needed bladder irrigation in the TURBT group. Compared with laser
      group, patients in the TURBT group had longer catheterization time and
      hospitalization duration. There were no statistical differences in the oncologic
      results in term of 2-year recurrence rates as compared between the two groups.
      CONCLUSIONS: Our study demonstrated that using KTP laser, transurethral
      vaporization is an effective and safe treatment for the patients with primary
      NMIBT. Compared with traditional TURBT, the KTP laser surgery had fewer
      perioperative complications and similar oncological results.

PMID- 25864417
TI  - Evaluation of the risks of chemotherapy in dogs with thrombocytopenia.
AB  - Thrombocytopenia is commonly encountered in veterinary oncology. Currently, there
      are no standard guidelines regarding the administration of chemotherapy to the
      patients with thrombocytopenia. This observational epidemiological cohort study
      aimed to determine whether thrombocytopenic dogs were at increased risk of
      gastrointestinal adverse effects (vomiting, diarrhoea, inappetence) or
      haemorrhage following administration of standard doses of chemotherapy. The
      adverse effects following 77 prospectively identified episodes of
      thrombocytopenia (platelet count, <200 000 uL-1 ) were compared with the adverse
      effects experienced in a retrospective cohort (platelet count >200 000 uL-1 ),
      and evaluated by statistical analysis. Overall, there was no statistically
      significant difference in the incidence of gastrointestinal adverse effects or
      haemorrhage between thrombocytopenic and control dogs. The control group of dogs
      with lymphoma were statistically more likely to experience vomiting as an adverse
      effect of chemotherapy (P = 0.028). The results presented here showed no evidence
      for an increased risk of gastrointestinal adverse effects or haemorrhage in
      thrombocytopenic dogs after receiving standard doses of chemotherapy.

PMID- 25864418
TI  - Characterization of the frequency and nature of bleed air contamination events in
      commercial aircraft.
AB  - Contamination of the bleed air used to pressurize and ventilate aircraft cabins
      is of concern due to the potential health and safety hazards for passengers and
      crew. Databases from the Federal Aviation Administration, NASA, and other sources
      were examined in detail to determine the frequency of bleed air contamination
      incidents. The frequency was examined on an aircraft model basis with the intent
      of identifying aircraft make and models with elevated frequencies of
      contamination events. The reported results herein may help investigators to focus
      future studies of bleed air contamination incidents on smaller number of
      aircrafts. Incident frequency was normalized by the number of aircraft, number of
      flights, and flight hours for each model to account for the large variations in
      the number of aircraft of different models. The focus of the study was on
      aircraft models that are currently in service and are used by major airlines in
      the United States. Incidents examined in this study include those related to
      smoke, oil odors, fumes, and any symptom that might be related to exposure to
      such contamination, reported by crew members, between 2007 and 2012, for US-based
      carriers for domestic flights and all international flights that either
      originated or terminated in the US. In addition to the reported frequency of
      incidents for different aircraft models, the analysis attempted to identify
      propulsion engines and auxiliary power units associated with aircrafts that had
      higher frequencies of incidents. While substantial variations were found in
      frequency of incidents, it was found that the contamination events were widely
      distributed across nearly all common models of aircraft.

PMID- 25864420
TI  - It's complicated - Factors predicting decisional conflict in prenatal diagnostic
      testing.
AB  - BACKGROUND: The technologies currently available to detect the presence of foetal
      genetic abnormalities are complex, and undergoing prenatal diagnostic testing can
      have wide-ranging repercussions. Before individuals can decide with certainty
      whether or not to take these tests, they first need to grasp the many
      psychosocial and clinical dimensions of prenatal genetic testing. OBJECTIVE: To
      test a model integrating key psychosocial and clinical factors as predictors of
      decisional conflict in decisions about whether or not to undergo prenatal genetic
      testing. METHOD: Adults (n = 457) read one of four hypothetical scenarios asking
      them to imagine expecting a child and considering the option of a prenatal test
      able to detect a genetic condition; age of condition onset (birth vs. adulthood)
      and its curability (no cure vs. curable) were manipulated. Participants completed
      measures of decisional conflict, perceived benefits from normal results, test
      response efficacy, condition coherence, child-related worry, perceived
      disagreement with the other parent's preference, motivation to comply with
      doctors' perceived preferences, and parity. RESULTS: Prenatal testing decisional
      conflict was positively predicted by perceiving normal results as beneficial,
      doubting the test's reliability, lacking understanding of the genetic condition,
      worrying about the health of the foetus, perceiving differences of opinion from
      partner/spouse, wanting to follow doctors' preferences, and being childless.
      DISCUSSION: These results, of growing relevance given the increasing availability
      of new technologies in pregnancy care, can inform communication strategies that
      facilitate couples' decision making. CONCLUSION: This study provides insights
      into factors that might complicate prenatal testing decision making.

PMID- 25864421
TI  - Divergent synthesis of chiral heterocycles via sequencing of enantioselective
      three-component reactions and one-pot subsequent cyclization reactions.
AB  - A highly efficient sequencing of catalytic asymmetric three-component reactions
      of alcohols, diazo compounds and aldimines/aldehydes with one-pot subsequent
      cyclization reactions was reported. The development of a robust and versatile
      Rh(ii)/Zr(iv)-BINOL co-catalytic system not only gives high diastereo- and
      enantioselective controls of the three-component reaction, but also shows
      excellent functionality tolerances that allow a wide range of functionalities to
      be pre-installed in each component and readily undergo one-pot subsequent
      cyclization reactions, thus providing rapid and diversity-oriented synthesis
      (DOS) of different types of chiral nitrogen- and/or oxygen-containing
      polyfunctional heterocycles. 

PMID- 25864422
TI  - [(18)F-FDG PET/CT in the evaluation of patients suspected of paraneoplastic
      neurological syndrome].
AB  - OBJECTIVE: This study aimed to determine the diagnostic impact of (18)F-FDG
      PET/CT based on the clinical features of paraneoplastic neurological syndrome
      (PNS). MATERIAL AND METHODS: Multicenter retrospective and longitudinal study of
      patients with suspicion of PNS. The clinical picture was classified into classic
      (CS) and non-classic syndrome (NCS). After the follow-up, the definitive or
      possible diagnosis of PNS was established. The pictures that did not match any of
      the previous criteria were categorized as non-classifiable. The state of the onco
      neural antibodies was studied. The PET/CT was classified as positive or negative
      for the detection of malignancy. The relationship between PET/CT findings and the
      final diagnosis was determined. The differences between variables (Pearson test
      X(2)) and the relationship between the results of the PET/CT and the final
      diagnosis were analyzed. RESULTS: A total of 64 patients were analyzed,
      classifying 30% as CS and 42% as NCS. After the follow-up, 20% and 16% of
      subjects were diagnosed as possible and definitive PNS, respectively. Positive
      onco-neural antibodies were found in 13% of the patients. A definitive diagnosis
      of PNS was associated with a positive PET/CT (P=.08). A significant relation
      between antibodies expression and final diagnosis of neoplasia (P=.04) was
      demonstrated. The PET/CT correctly localized malignancy in 5/7 cases of invasive
      cancer. CONCLUSIONS: The PET/CT showed a higher percentage of positive results in
      patients with definitive diagnosis of PNS. Despite the low prevalence of
      malignancy in our series, the PET/CT detected malignancy in a significant
      proportion of patients with invasive cancer.

PMID- 25864423
TI  - Crystal structure of the fungal nitroreductase Frm2 from Saccharomyces
      cerevisiae.
AB  - Nitroreductases are flavoenzymes that catalyze nitrocompounds and are widely
      utilized in industrial applications due to their detoxification potential and
      activation of biomedicinal prodrugs. Type I nitroreductases are classified into
      subgroups depending on the use of NADPH or NADH as the electron donor. Here, we
      report the crystal structure of the fungal nitroreductase Frm2 from Saccharomyces
      cerevisiae, one of the uncharacterized subgroups of proteins, to reveal its
      minimal architecture previously observed in bacterial nitroreductases such as
      CinD and YdjA. The structure lacks protruding helical motifs that form part of
      the cofactor and substrate binding site, resulting in an open and wide active
      site geometry. Arg82 is uniquely conserved in proximity to the substrate binding
      site in Frm2 homologues and plays a crucial role in the activity of the active
      site. Frm2 primarily utilizes NADH to reduce 4-NQO. Because missing helical
      elements are involved in the direct binding to the NAD(P)H in group A or group B
      in Type I family, Frm2 and its homologues may represent a distinctive subgroup
      with an altered binding mode for the reducing compound. This result provides a
      structural basis for the rational design of novel prodrugs with the ability to
      reduce nitrogen-containing hazardous molecules. 

PMID- 25864424
TI  - Genome analysis of a novel, highly divergent picornavirus from common kestrel
      (Falco tinnunculus): the first non-enteroviral picornavirus with type-I-like
      IRES.
AB  - Although the number of identified avian-borne picornaviruses (family
      Picornaviridae) is continuously increasing there remains several species-rich
      avian host groups, such as the order Falconiformes (with 290 bird species) from
      which picornaviruses have not been identified. This study reports the first
      complete genome of a novel, highly divergent picornavirus, named as Falcovirus A1
      (KP230449), from the carnivorous bird, the common kestrel (Falco tinnunculus,
      order Falconiformes). Falcovirus A1 has the longest 3D(RdRp) genome region and
      distant phylogenetic relationship to the Hepatitis A virus 1 (Hepatovirus) and
      Avian encephalomyelitis virus 1 (Tremovirus). It has a type-I (enterovirus-like)
      IRES in the 5'UTR - identified for the first time among avian-borne
      picornaviruses suggesting that type-I IRES is not restricted only to
      enteroviruses and providing further evidence of mosaicism of this region among
      different picornavirus genera.

PMID- 25864425
TI  - Antidepressant-like effects of oleoylethanolamide in a mouse model of chronic
      unpredictable mild stress.
AB  - Oleoylethanolamide (OEA) is an endocannabinoid analog that belongs to a family of
      endogenous acylethanolamides. Increasing evidence suggests that OEA may act as an
      endogenous neuroprotective factor and participate in the control of mental
      disorder-related behaviors. In this study, we examined whether OEA is effective
      against depression and investigated the role of circulating endogenous
      acylethanolamides during stress. Mice were subjected to 28days of chronic
      unpredictable mild stress (CUMS), and during the last 21days, treated with oral
      OEA (1.5-6mg/kg) or 6mg/kg fluoxetine. Sucrose preference and open field test
      activity were used to evaluate depression-like behaviors during CUMS and after
      OEA treatment. Weights of the prefrontal cortex and hippocampus were determined,
      and the adrenal index was measured. Furthermore, changes in serum
      adrenocorticotropic hormone (ACTH), corticosterone (CORT) and total antioxidant
      capacity (T-AOC), brain-derived neurotrophic factor (BDNF), and lipid
      peroxidation product malondialdehyde (MDA) levels, and superoxide dismutase (SOD)
      activities in the hippocampus and prefrontal cortex were detected. Our findings
      indicate that OEA normalized sucrose preferences, locomotion distances, rearing
      frequencies, prefrontal cortex and hippocampal atrophy, and adrenal indices. In
      addition, OEA reversed the abnormalities of BDNF and MDA levels and SOD
      activities in the hippocampus and prefrontal cortex, as well as changes in serum
      levels of ACTH, CORT, and T-AOC. The antidepressant effects of OEA may be related
      to the regulation of BDNF levels in the hippocampus and prefrontal cortex,
      antioxidant defenses, and normalizing hyperactivity in the hypothalamic-pituitary
      adrenal axis (HPA). 

PMID- 25864426
TI  - Effect of solution and leaf surface polarity on droplet spread area and contact
      angle.
AB  - BACKGROUND: How much an agrochemical spray droplet spreads on a leaf surface can
      significantly influence efficacy. This study investigates the effect solution
      polarity has on droplet spreading on leaf surfaces and whether the relative leaf
      surface polarity, as quantified using the wetting tension dielectric (WTD)
      technique, influences the final spread area. Contact angles and spread areas were
      measured using four probe solutions on 17 species. RESULTS: Probe solution
      polarity was found to affect the measured spread area and the contact angle of
      the droplets on non-hairy leaves. Leaf hairs skewed the spread area measurement,
      preventing investigation of the influence of surface polarity on hairy leaves.
      WTD-measured leaf surface polarity of non-hairy leaves was found to correlate
      strongly with the effect of solution polarity on spread area. CONCLUSIONS: For
      non-polar leaf surfaces the spread area decreases with increasing solution
      polarity, for neutral surfaces polarity has no effect on spread area and for
      polar leaf surfaces the spread area increases with increasing solution polarity.
      These results attest to the use of the WTD technique as a means to quantify leaf
      surface polarity. (c) 2015 Society of Chemical Industry.

PMID- 25864427
TI  - A Gain-of-Function Mutation in NALCN in a Child with Intellectual Disability,
      Ataxia, and Arthrogryposis.
AB  - NALCN and its homologues code for the ion channel responsible for half of
      background Na(+) -leak conductance in vertebrate and invertebrate neurons.
      Recessive mutations in human NALCN cause intellectual disability (ID) with
      hypotonia. Here, we report a de novo heterozygous mutation in NALCN affecting a
      conserved residue (p.R1181Q) in a girl with ID, episodic and persistent ataxia,
      and arthrogryposis. Interestingly, her episodes of ataxia were abolished by the
      administration of acetazolamide, similar to the response observed in episodic
      ataxia associated with other ion channels. Introducing the analogous mutation in
      the Caenorhabditis elegans homologue nca-1 induced a coiling locomotion
      phenotype, identical to that obtained with previously characterized C. elegans
      gain-of-function nca alleles, suggesting that p.R1181Q confers the same property
      to NALCN. This observation thus suggests that dominant mutations in NALCN can
      cause a neurodevelopmental phenotype that overlaps with, while being mostly
      distinct from that associated with recessive mutations in the same gene. 

PMID- 25864428
TI  - Live attenuated influenza vaccine tetravalent: a clinical review.
AB  - Live attenuated influenza vaccine (LAIV) has been available as a trivalent
      formulation in the EU since 2012. Influenza B strains from two lineages have co
      circulated outside Asia in Europe, Israel and North America since the early
      2000s. The trivalent vaccine contained a single influenza B lineage virus chosen
      primarily on the basis of the previous year's circulating lineage. Failure to
      align the vaccine virus with the circulating virus leaves even vaccinated
      patients, particularly children, at risk for infection with B viruses from the
      other lineage. Recently, a tetravalent formulation was approved and use will
      begin during the 2014-2015 influenza season. Approval of LAIV Tetra was based on
      the established efficacy and safety of trivalent LAIV and studies demonstrating
      similar immunogenicity between the trivalent and tetravalent vaccines. Addition
      of a fourth strain to the vaccine will address the issue of co-circulation of
      influenza B viruses and provide a broader range of protection. 

PMID- 25864430
TI  - Effects of two whole-grain barley varieties on caecal SCFA, gut microbiota and
      plasma inflammatory markers in rats consuming low- and high-fat diets.
AB  - Mixed-linkage beta-glucans are fermented by the colon microbiota that give rise
      to SCFA. Propionic and butyric acids have been found to play an important role in
      colonic health, as well as they may have extraintestinal metabolic effects. The
      aim of the present study was to investigate how two whole-grain barley varieties
      differing in dietary fibre and beta-glucan content affected caecal SCFA, gut
      microbiota and some plasma inflammatory markers in rats consuming low-fat (LF) or
      high-fat (HF) diets. Barley increased the caecal pool of SCFA in rats fed the LF
      and HF diets compared with those fed the control diet, and the effect was
      generally dependent on fibre content, an exception was butyric acid in the LF
      setting. Furthermore, whole-grain barley reduced plasma lipopolysaccharide
      binding protein and monocyte chemoattractant protein-1, increased the caecal
      abundance of Lactobacillus and decreased the Bacteroides fragilis group, but
      increased the number of Bifidobacterium only when dietary fat was consumed at a
      low level. Fat content influenced the effects of barley: rats fed the HF diets
      had a higher caecal pool of acetic and propionic acids, higher concentrations of
      amino acids and higher amounts of lipids in the portal plasma and liver than rats
      fed the LF diets; however, less amounts of butyric acid were generally formed.
      Interestingly, there was an increase in the caecal abundance of Akkermansia and
      the caecal pool of succinic acid, and a decrease in the proportion of
      Bifidobacterium and the Clostridium leptum group. In summary, whole-grain barley
      decreased HF diet-induced inflammation, which was possibly related to the
      formation of SCFA and changes in microbiota composition. High beta-glucan content
      in the diet was associated with reduced plasma cholesterol levels. 

PMID- 25864429
TI  - p35 and Rac1 underlie the neuroprotection and cognitive improvement induced by
      CDK5 silencing.
AB  - CDK5 plays an important role in neurotransmission and synaptic plasticity in the
      normal function of the adult brain, and dysregulation can lead to Tau
      hyperphosphorylation and cognitive impairment. In a previous study, we
      demonstrated that RNAi knock down of CDK5 reduced the formation of
      neurofibrillary tangles (NFT) and prevented neuronal loss in triple transgenic
      Alzheimer's mice. Here, we report that CDK5 RNAi protected against glutamate
      mediated excitotoxicity using primary hippocampal neurons transduced with adeno
      associated virus 2.5 viral vector eGFP-tagged scrambled or CDK5 shRNA-miR during
      12 days. Protection was dependent on a concomitant increase in p35 and was
      reversed using p35 RNAi, which affected the down-stream Rho GTPase activity.
      Furthermore, p35 over-expression and constitutively active Rac1 mimicked CDK5
      silencing-induced neuroprotection. In addition, 3xTg-Alzheimer's disease mice (24
      months old) were injected in the hippocampus with scrambled or CDK5 shRNA-miR,
      and spatial learning and memory were performed 3 weeks post-injection using
      'Morris' water maze test. Our data showed that CDK5 knock down induced an
      increase in p35 protein levels and Rac activity in triple transgenic Alzheimer's
      mice, which correlated with the recovery of cognitive function; these findings
      confirm that increased p35 and active Rac are involved in neuroprotection. In
      summary, our data suggest that p35 acts as a mediator of Rho GTPase activity and
      contributes to the neuroprotection induced by CDK5 RNAi.

PMID- 25864431
TI  - Relationship of glomerular filtration rate based on serum iodixanol clearance to
      IRIS staging in cats with chronic kidney disease.
AB  - We examined the correlation between the glomerular filtration rate (GFR)
      estimated from an equation based on the serum iodixanol clearance technique and
      International Renal Interest Society (IRIS) stages of chronic kidney disease
      (CKD) in cats. The equation included the injection dose, sampling time, serum
      concentration and estimated volume of distribution (Vd) of the isotonic,
      nonionic, contrast medium iodixanol as a test tracer. The percent changes in the
      median basal GFR values calculated from the equation in CKD cats resembled those
      of IRIS stages 1-3. These data validate the association between the GFR derived
      from the simplified equation and IRIS stages based on the serum creatinine
      concentration in cats with CKD. They describe the GFR ranges determined using
      single-sample iodixanol clearance for healthy cats and cats with various IRIS
      stages of CKD. 

PMID- 25864432
TI  - Defining minimum essential factors to derive highly pure human endothelial cells
      from iPS/ES cells in an animal substance-free system.
AB  - It is desirable to obtain unlimited supplies of endothelial cells for research
      and therapeutics. However, current methods of deriving endothelial cells from
      humans suffer from issues, such as limited supplies, contamination from animal
      substances, and lengthy/complicated procedures. In this article we developed a
      way to differentiate human iPS and ES cells to highly pure endothelial cells in 5
      days. The chemically defined system is robust, easy to perform, and free of
      animal substances. Using the system, we verified that combined TGFbeta and
      canonical Wnt agonists are essential and sufficient for iPS/ES cell-to-mesoderm
      transition. Besides, VEGF-KDR signaling alone is required for endothelial
      formation at high density while supplementation with FGF allows for colonial
      endothelial differentiation. Finally, anti-adsorptive agents could enrich the
      endothelial output by allowing selective attachment of the endothelial
      precursors. The system was validated to work on multiple iPS/ES cells lines to
      produce endothelial cells capable of forming capillary-like structures in vitro
      and integrating into host vasculature in vivo. In sum, the simple yet robust
      differentiation system permits the unlimited supply of human endothelial cells.
      The defined and animal substance-free nature of the system is compatible with
      clinical applications and characterization of endothelial differentiation in an
      unbiased manner. 

PMID- 25864433
TI  - Effects of the COPE Cognitive Behavioral Skills Building TEEN Program on the
      Healthy Lifestyle Behaviors and Mental Health of Appalachian Early Adolescents.
AB  - INTRODUCTION: Appalachian adolescents have a high prevalence of obesity and
      mental health problems that exceed national rates, with the two conditions often
      co-existing. The purpose of this study was to evaluate the feasibility and
      preliminary efficacy of a 15-session cognitive-behavioral skills building
      intervention (COPE [Creating Opportunities for Personal Empowerment] Healthy
      Lifestyles TEEN [Thinking, Emotions, Exercise, and Nutrition] Program) on healthy
      lifestyle behaviors, physical health, and mental health of rural early
      adolescents. METHODS: A pre- and posttest pre-experimental design was used with
      follow-up immediately after the intervention. RESULTS: Results support
      improvement in the students' anxiety, depression, disruptive behavior, and self
      concept scores after the COPE intervention compared with baseline. Additionally,
      healthy lifestyle behavior scores improved before the intervention compared with
      after the intervention. DISCUSSION: COPE is a promising intervention that
      improves mental health and healthy lifestyle behaviors and can be integrated
      routinely into school-based settings.

PMID- 25864434
TI  - Priorities for global felid conservation.
AB  - Conservation resources are limited, necessitating prioritization of species and
      locations for action. Most prioritization approaches are based solely on
      biologically relevant characteristics of taxa or areas and ignore geopolitical
      realities. Doing so risks a poor return on conservation investment due to
      nonbiological factors, such as economic or political instability. We considered
      felids, a taxon which attracts intense conservation attention, to demonstrate a
      new approach that incorporates both intrinsic species traits and geopolitical
      characteristics of countries. We developed conservation priority scores for wild
      felids based on their International Union for Conservation of Nature status, body
      mass, habitat, range within protected area, evolutionary distinctiveness, and
      conservation umbrella potential. We used published data on governance, economics
      and welfare, human population pressures, and conservation policy to assign
      conservation-likelihood scores to 142 felid-hosting countries. We identified 71
      countries as high priorities (above median) for felid conservation. These
      countries collectively encompassed all 36 felid species and supported an average
      of 96% of each species' range. Of these countries, 60.6% had below-average
      conservation-likelihood scores, which indicated these countries are relatively
      risky conservation investments. Governance was the most common factor limiting
      conservation likelihood. It was the major contributor to below-median likelihood
      scores for 62.5% of the 32 felid species occurring in lower-likelihood countries.
      Governance was followed by economics for which scores were below median for 25%
      of these species. An average of 58% of species' ranges occurred in 43 higher
      priority lower-likelihood countries. Human population pressure was second to
      governance as a limiting factor when accounting for percentage of species' ranges
      in each country. As conservation likelihood decreases, it will be increasingly
      important to identify relevant geopolitical limitations and tailor conservation
      strategies accordingly. Our analysis provides an objective framework for
      biodiversity conservation action planning. Our results highlight not only which
      species most urgently require conservation action and which countries should be
      prioritized for such action, but also the diverse constraints which must be
      overcome to maximize long-term success.

PMID- 25864435
TI  - Detection and Clinical Significance of Sternal Lesions on Breast MRI.
AB  - The purpose of this study is to characterize sternal lesions detected on breast
      magnetic resonance imaging (MRI), compare MRI detection of sternal lesions with
      other imaging modalities (bone scan, positron emission tomography/computed
      tomography (PET/CT) and chest CT), and ascertain how often patient management is
      altered by discovery of sternal lesions. Retrospective review of 1143 breast MRIs
      between 2007 and 2012 identified 17 patients with sternal lesions including 15
      patients with newly diagnosed breast cancer and two patients with remote history
      of breast cancer. Tumor size, histopathology, receptor status, nodal and distant
      metastasis, and images of breast MRI, and other modalities were reviewed. Sternal
      lesions in 9 of the 17 patients were determined to be malignant (metastasis)
      either by biopsy or presence of widespread metastases. Sternal lesions in 8 of
      the 17 were benign, confirmed by biopsy or presumed benign as not detected by
      other modalities. The malignant group had statistically significant larger breast
      cancer size (malignant: 6.4 cm; benign: 2.3 cm), a higher percentage of diffuse
      sternal lesions (malignant: 56%; benign: 0%), and more frequently showed rapid
      initial enhancing (malignant: 100%; benign: 63%) and delayed washout curves
      (malignant: 67%; benign: 13%). Although not statistically significant, the
      malignant group had a higher frequency of invasive lobular carcinoma (malignant:
      44%; benign: 13%) and more lymph node involvement (malignant: 78%; benign: 50%).
      Breast MRI detected more sternal lesions than did bone scan, PET/CT and chest CT.
      Four of the 17 (24%) patients were upgraded to stage 4 due to unsuspected
      metastatic sternal lesions on breast MRI. In conclusion, breast MRI is more
      sensitive than other modalities in detecting sternal lesions. Sternal metastases
      occur more frequently in aggressive breast cancer and exhibit malignant-type
      dynamics on breast MRI. Detection of unsuspected sternal metastasis alters
      staging and improves patient management with more appropriate treatment.

PMID- 25864436
TI  - H8-BINOL chiral imidodiphosphoric acid catalyzed highly enantioselective aza
      Friedel-Crafts reactions of pyrroles and enamides/imines.
AB  - The first enantioselective aza-Friedel-Crafts reaction between pyrroles and
      enamides has been achieved by using a novel H8-BINOL-type imidodiphosphoric acid
      catalyst. This methodology was also applied to the highly enantioselective aza
      Friedel-Crafts reaction between pyrroles and imines. The catalyst loadings in
      these two reactions are low (0.3-2 mol%). Both processes are amenable to gram
      scales. 

PMID- 25864438
TI  - Ranging and site fidelity in northern pigtailed macaques (Macaca leonina) over
      different temporal scales.
AB  - Space-use patterns are crucial to understanding the ecology, evolution, and
      conservation of primates, but detailed ranging data are scarce for many species,
      especially those in Southeast Asia. Researchers studying site fidelity to either
      home ranges or core areas have focused mainly on territorial species, whereas
      less information is available for non-territorial species. We analyzed the
      ranging patterns and site fidelity of one wild troop of northern pigtailed
      macaques over 16 months at different temporal scales. We used characteristic hull
      polygons in combination with spatial statistics to estimate home ranges and core
      areas. The total home range and core areas were 449 ha and 190 ha, respectively.
      Average daily path length was 2,246 m. The macaques showed a high defendabili--ty
      index according to the expected ranging of a non-territorial species in which
      movement does not theoretically permit the defense of a large territory. Overall,
      the study troop ranged more extensively than conspecific groups and closely
      related species studied elsewhere. These differences may reflect variable troop
      size, degree of terrestriality and habitat characteristics, but could also
      reflect methodological differences. The location, size and shape of home ranges
      and core areas, and extent of daily path lengths changed on a monthly basis
      resulting in low site fidelity between months. The macaques also showed clear
      shifts in the location of daily home ranges with low site fidelity scores between
      consecutive days. Daily home range and daily path length were related to
      seasonality, with greater values during the fruit-abundant period. Low site
      fidelity associated with lack of territoriality is consistent with macaques
      structuring their movement based on available food sources. However, ranging
      patterns and site fidelity can also be explained by macaques feeding on the move,
      a foraging strategy that hinders frequent and long visits to the same location.

PMID- 25864440
TI  - Perfusion CT imaging of treatment response in oncology.
AB  - Perfusion CT was first described in the 1970s but has become accepted as a
      clinical technique in recent years. In oncological practice Perfusion CT allows
      the downstream effects of therapies on the tumour vasculature to be monitored.
      From the dynamic changes in tumour and vascular enhancement following intravenous
      iodinated contrast agent administration, qualitative and quantitative parameters
      may be derived that reflect tumour perfusion, blood volume, and microcirculatory
      changes with treatment. This review outlines the mechanisms of action of
      available therapies and state-of-the-art imaging practice. 

PMID- 25864441
TI  - Performance of FLT-PET for pulmonary lesion diagnosis compared with traditional
      FDG-PET: A meta-analysis.
AB  - PURPOSE: Widely used (18)F 2'-deoxy-2'-fluoro-d-glucose (FDG) positron emission
      tomography (PET) can be problematic with false positives in cancer imaging. This
      study aims to investigate the diagnostic accuracy of a candidate PET tracer,
      (18)F 2',3'-dideoxy-3'-fluoro-2-thiothymidine (FLT), in diagnosing pulmonary
      lesions compared with FDG. MATERIALS AND METHODS: After comprehensive search and
      study selection, a meta-analysis was performed on data from 548 patients pooled
      from 17 studies for evaluating FLT accuracy, in which data from 351 patients
      pooled from ten double-tracer studies was used for direct comparison with FDG.
      Weighted sensitivity and specificity were used as main indicators of test
      performance. Individual data was extracted and patient subgroup analyses were
      performed. RESULTS: Overall, direct comparisons showed lower sensitivity (0.80
      vs. 0.89) yet higher specificity (0.82 vs. 0.66) for FLT compared with FDG (both
      p<0.01). Patient subgroup analysis showed FLT was less sensitive than FDG in
      detecting lung cancers staged as T1 or T2, and those <=2.0 cm in diameter (0.81
      vs. 0.93, and 0.53 vs. 0.78, respectively, both p<0.05), but was comparable for
      cancers staged as T3 or T4, and those >2.0 cm in diameter (0.95 vs. 1.00, 0.96
      vs. 0.88, both p>0.05). For benignities, FLT performed better compared with FDG
      in ruling out inflammation-based lesions (0.57 vs. 0.32, p<0.05), and
      demonstrated greater specificity regardless of lesion sizes. CONCLUSIONS:
      Although FLT cannot replace FDG in detecting small and early lung cancers, it may
      help to prevent patients with larger or inflammatory lesions from cancer
      misdiagnosis or even over-treatment.

PMID- 25864439
TI  - What to compare and how: Comparative transcriptomics for Evo-Devo.
AB  - Evolutionary developmental biology has grown historically from the capacity to
      relate patterns of evolution in anatomy to patterns of evolution of expression of
      specific genes, whether between very distantly related species, or very closely
      related species or populations. Scaling up such studies by taking advantage of
      modern transcriptomics brings promising improvements, allowing us to estimate the
      overall impact and molecular mechanisms of convergence, constraint or innovation
      in anatomy and development. But it also presents major challenges, including the
      computational definitions of anatomical homology and of organ function, the
      criteria for the comparison of developmental stages, the annotation of
      transcriptomics data to proper anatomical and developmental terms, and the
      statistical methods to compare transcriptomic data between species to highlight
      significant conservation or changes. In this article, we review these challenges,
      and the ongoing efforts to address them, which are emerging from bioinformatics
      work on ontologies, evolutionary statistics, and data curation, with a focus on
      their implementation in the context of the development of our database Bgee
      (http://bgee.org).

PMID- 25864442
TI  - Stability and solubility of trans-resveratrol are strongly influenced by pH and
      temperature.
AB  - Recently trans-resveratrol (trans-RSV) has received great attention due to its
      prophylactic and therapeutic properties. Its limited bioavailability provides
      compelling evidence of the need for more suitable formulations in order to attain
      better clinical effectiveness. Some physicochemical properties of trans-RSV are
      still unknown or research findings are contradictory. Therefore, this paper
      presents newly determined trans-RSV solubility and stability at various pH and
      temperatures, and the importance of such data for the studies of novel trans-RSV
      loaded nanofibers. In acidic pH trans-RSV was stable, whereas its degradation
      started to increase exponentially above pH 6.8. Consequently, it is worthwhile to
      note that special consideration has to be dedicated to long dissolution testing
      or biological assays on cell lines in order to obtain relevant data. Measurements
      were done by validated UV/VIS spectroscopy, HPLC, and newly developed UPLC
      methods. Specificity was confirmed for HPLC and UPLC method, whereas UV/VIS
      spectroscopy resulted in false higher trans-RSV concentrations in conditions
      under which it was not stable (alkaline pH, light, increased temperature). The
      study is of interest because it draws attention to the importance of careful
      selected experimental conditions, their influence on the trans-RSV stability and
      the implications this has for formulation development, storage, and maintenance
      of therapeutic doses. 

PMID- 25864443
TI  - Anticancer activity of galactoxyloglucan polysaccharide-conjugated doxorubicin
      nanoparticles: Mechanistic insights and interactome analysis.
AB  - Toxicity associated with chemotherapeutic drugs such as doxorubicin (Dox), is one
      of the major obstacles that is currently affecting patients. PST-Dox
      (Galactoxyloglucan, PST001-conjugated Dox) nanoparticles were synthesized by
      encapsulating Dox with polysaccharide PST001, isolated from Tamarindus indica
      (Ti) by ionic gelation with tripolyphosphate (TPP). Herein, we demonstrate a
      detailed mechanistic and interactome network analysis that is specific to PST-Dox
      action in cancer cells and normal lymphocytes. Our results show that PST-Dox is
      superior to its parental counterparts, exhibiting a greater cytotoxicity by the
      induction of apoptosis against a wide variety of cancers by enhanced cellular
      uptake of Dox from the nanoparticle conjugates. Also, PST-Dox nanoparticles were
      non-toxic to normal lymphocytes with limited immunostimulatory effects up to
      certain doses. Elucidation of molecular mechanism by whole genome microarray in
      cancer cells and lymphocytes revealed that a large number of genes were
      dysregulated specifically in cancer cells. Specifically, a unique target gene
      EGR1, contextually determined translational activation of P53 in the cancerous
      and non-cancerous cells. Most of the key downregulated genes were tyrosine
      kinases, indicating the potential inhibitory action of PST-Dox on tyrosine kinase
      oncogenic pathways. Western blotting of proteins corresponding to the genes that
      were altered at the genomic level was very well correlated in the majority of
      them, except in a few that demonstrated post-transcriptional modifications. The
      important findings and highly disciplined approaches highlighted in the present
      study will speed up the therapeutic potential of this augmented nanoparticle
      formulation for more robust clinical studies and testing in several cancers. 

PMID- 25864445
TI  - Enhanced extraction of proteins using cholinium-based ionic liquids as phase
      forming components of aqueous biphasic systems.
AB  - Aqueous biphasic systems (ABS) composed of ionic liquids (ILs) are promising
      platforms for the extraction and purification of proteins. In this work, a series
      of alternative and biocompatible ABS composed of cholinium-based ILs and
      polypropylene glycol were investigated. The respective ternary phase diagrams,
      tie-lines, tie-line lengths and critical points were determined at 25 degrees C.
      The extraction performance of these systems for commercial bovine serum albumin
      (BSA) was then evaluated. The stability of BSA at the IL-rich phase was
      ascertained by size exclusion high-performance liquid chromatography and Fourier
      transform infrared spectroscopy. Appropriate ILs lead to the complete extraction
      of BSA for the IL-rich phase, in a single step, while maintaining the protein's
      native conformation. Furthermore, to evaluate the performance of these systems
      when applied to real matrices, the extraction of BSA from bovine serum was
      additionally carried out, revealing that the complete extraction of BSA was
      maintained and achieved in a single step. The remarkable extraction efficiencies
      obtained are far superior to those observed with typical polymer-based ABS.
      Therefore, the proposed ABS may be envisaged as a more effective and
      biocompatible approach for the separation and purification of other value-added
      proteins. 

PMID- 25864444
TI  - Lesions targeted to the anterior forebrain disrupt vocal variability associated
      with testosterone-induced sensorimotor song development in adult female canaries,
      Serinus canaria.
AB  - Learned communication was a trait observed in a limited number of vertebrates
      such as humans but also songbirds (i.e., species in the suborder passeri
      sometimes called oscines). Robust male-biased sex-differences in song development
      and production have been observed in several songbird species. However, in some
      of these species treating adult females with testosterone (T) induced neuro
      behavioral changes such that females become more male-like in brain and behavior.
      T-treatment in these adult females seemed to stimulate sensorimotor song
      development to facilitate song masculinization. In male songbirds it was known
      that the lateral magnocellular nucleus of the anterior nidopallium (LMAN) played
      a modulatory role during song development. LMAN was androgen sensitive and may be
      a key target of a T-induced recapitulation of a developmental process in adult
      females. This hypothesis was tested. Adult female canaries were given either a
      chemical lesion of LMAN or a control sham-surgery. Prior to surgery birds were
      individually housed for 2-weeks in sound-attenuated chambers to record baseline
      vocal behavior. Post-surgery birds were given 1-week to recover before
      subcutaneous implantation with silastic capsules filled with crystalline-T. Birds
      remained on treatment for 3-weeks (behavioral recordings continued throughout).
      Birds with a lesion to LMAN had less variability in their song compared with
      controls. The diversity of syllable and phrase type(s) was greater in sham
      controls as compared with birds with LMAN lesions. Birds did not differ in song
      rate. These data suggested that the sustention and conclusion of T-induced
      sensorimotor song development in adult female canaries required an intact LMAN.

PMID- 25864446
TI  - [European health systems to examine].

PMID- 25864447
TI  - Allergic contact dermatitis caused by prednicarbate presenting as chronic hand
      eczema.

PMID- 25864448
TI  - B-Type Natriuretic Peptide Levels Predict Ventricular Arrhythmia Post Left
      Ventricular Assist Device Implantation.
AB  - B-type natriuretic peptide (BNP) levels have been shown to predict ventricular
      arrhythmia (VA) and sudden death in patients with heart failure. We sought to
      determine whether BNP levels before left ventricular assist device (LVAD)
      implantation can predict VA post LVAD implantation in advanced heart failure
      patients. We conducted a retrospective study consisting of patients who underwent
      LVAD implantation in our institution during the period of May 2009-March 2013.
      The study was limited to patients receiving a HeartMate II or HeartWare LVAD.
      Acute myocardial infarction patients were excluded. We compared between the
      patients who developed VA within 15 days post LVAD implantation to the patients
      without VA. A total of 85 patients underwent LVAD implantation during the study
      period. Eleven patients were excluded (five acute MI, four without BNP
      measurements, and two discharged earlier than 13 days post LVAD implantation).
      The incidence of VA was 31%, with 91% ventricular tachycardia (VT) and 9%
      ventricular fibrillation. BNP remained the single most powerful predictor of VA
      even after adjustment for other borderline significant factors in a multivariate
      logistic regression model (P < 0.05). BNP levels are a strong predictor of VA
      post LVAD implantation, surpassing previously described risk factors such as age
      and VT in the past. 

PMID- 25864449
TI  - Detection of Extended-Spectrum beta-Lactamase and Plasmid-Mediated Quinolone
      Resistance Determinants in Escherichia coli Isolates from Retail Meat in China.
AB  - The aim of this study was to investigate the presence of extended-spectrum beta
      lactamase (ESBL) and plasmid-mediated quinolone resistance (PMQR) genes in
      Escherichia coli isolated from retail meat samples in Henan Province, China. E.
      coli isolates were detected in 179 of 645 (27.7%) retail meat samples. Resistance
      of these isolates to antimicrobials was commonly observed, with 78.2% of isolates
      resistant to streptomycin, 74.3% resistant to tetracycline and 54.2% resistant to
      trimethoprim/sulfamethoxazole. Of the 179 isolates, 30 (16.7%) expressed ESBL,
      with blaTEM-1 (n = 17) and bla(CTX-M-14) (n = 9) most commonly mediating the ESBL
      phenotype. PMQR genes were present in 14 isolates (7.8%), with qnr and aac(6')-Ib
      cr detected alone or in combination in nine (5.0%) and seven isolates (3.9%),
      respectively. The qnr genes detected included qnrS1 (n = 5), qnrA1 (n = 3), and
      qnrB4 (n = 1). The qepA gene was absent among these isolates. CTX-M-14 was the
      most prevalent ESBL type among the PMQR-positive isolates. The qnr and aac(6')-Ib
      cr genes were found to co-reside and be co-transferred with blaCTX-M-14 or blaTEM
      1 in five isolates. Our data suggest that retail meat may act as a reservoir for
      multi-resistant E. coli and may facilitate the dissemination of resistance genes.

PMID- 25864450
TI  - Decreased endothelin-1 plasma levels in multiple sclerosis patients: a possible
      factor of vascular dysregulation?
AB  - BACKGROUND: Multiple sclerosis (MS) is a demyelinating autoimmune disease of the
      central nervous system with possible involvement of vascular dysregulation
      secondary to endothelial dysfunction caused by destruction of the vessel wall.
      Vascular dysregulation leads to excessive vasoconstriction or insufficient
      vasodilatation, resulting in vasospasm mediated by endothelin-1 (ET-1), the most
      potent and long-lasting mediator. Vascular dysregulation can play an important
      role in the pathogenesis of some eye disorders and it has been hypothesized that
      it is a vascular risk factor for glaucomatous optic neuropathy. The aim of this
      study was to estimate endothelin-1 (ET-1) plasma levels in patients with MS.
      MATERIAL AND METHODS: The MS group consisted of 39 patients (9 males, 30
      females), mean age: 38.8 +/- 10.02 years, range: 22-62. The control group
      consisted of 27 healthy volunteers (3 males and 24 females), mean age: 37.4 +/-
      10.88 years, range: 20-62; clinically, in a non-active stage of the disease. ET-1
      plasma levels were measured using the Endothelin-1 ELISA Kit (Immuno-Biological
      Laboratories Co., Japan). Statistical analysis was performed with the
      nonparametric Mann-Whitney U test for independent groups. RESULTS: Endothelin-1
      (ET-1) plasma levels were significantly lower in MS patients compared to healthy
      controls: mean value 0.55 +/- 0.44 pg/ml (146.05 +/- 118.27 fmol/ml) vs. 0.95 +/-
      0.48 pg/ml (252.83 +/- 127.16 fmol/ml); P=0.012. CONCLUSIONS: Significantly
      decreased ET-1 plasma levels in the MS patients could reflect the non-active
      disease at the time of ET-1 measurements or the effects of immunomodulatory
      treatment, but it cannot be excluded that decreased ET-1 plasma levels in these
      patients might result from vascular dysregulation.

PMID- 25864452
TI  - Evolution of germline segregation processes in animal development.
AB  - Germline segregation is a complex process by which germline cells are separated
      from somatic tissues during development. Recent animal studies on germline
      segregation allow for comparisons of the mechanisms used by different species and
      to propose evolutionary scenarios underlying the diversification of these
      processes. In this review, several proposed models of germline segregation are
      presented, and in addition, recent findings from the increasing number of studies
      are discussed, particularly concerning the need to reconsider these models based
      on available data. 

PMID- 25864451
TI  - Course of alcohol symptoms and social anxiety disorder from adolescence to young
      adulthood.
AB  - BACKGROUND: There is limited knowledge of the course of social anxiety disorder
      (SAD) from adolescence into adulthood, and how SAD and alcohol use disorder (AUD)
      symptoms change together over time. The current study examined how persistent and
      adolescent-limited SAD relate to alcohol symptom trajectories across adolescence
      and into adulthood, as well as gender differences in the course of SAD and AUD
      symptoms. METHODS: Participants were 788 youth (ages 12 to 18 at the baseline
      assessment; 46.2% female; 80.5% White) recruited from the community (n = 220) and
      from clinical programs (n = 568). Youth completed clinical interviews on their
      lifetime history of AUD symptoms and SAD at baseline and were followed through
      age 25. Multivariate polynomial growth mixture modeling was used to estimate
      developmental trajectories for SAD and AUD symptoms separately, then together in
      a dual trajectory model. Gender differences were examined using a classify
      analyze approach. RESULTS: Three SAD trajectory classes were identified:
      adolescent-limited (15%), persistent (6%), and no SAD (79%). For AUD symptoms, 5
      trajectories were identified: severe (10%), moderate (22%), remitting (18%),
      young adult onset (22%), and stable low (28%). Those with a history of SAD were
      about twice as likely to be in the severe AUD symptom class compared to those
      without a history of SAD. Compared to those with persisting SAD, those in the
      adolescent-limited SAD class were more likely to belong to the stable low AUD
      trajectory. Compared to males with SAD, females with SAD were less likely to be
      in the moderate AUD symptom class and were more likely to be in stable low and
      young adult onset AUD symptom classes. CONCLUSIONS: A history of SAD was
      associated with membership in the severe AUD trajectory group. The association of
      gender with SAD and AUD differed depending on developmental period. Future
      research should examine whether treating SAD in early adolescence may prevent
      subsequent AUD symptoms.

PMID- 25864453
TI  - What kind of thing is depression?

PMID- 25864454
TI  - Distinctive Hemodynamics in the Immediate Postoperative Period of Patients with a
      Longer Cardiac Intensive Care Stay Post-Tetralogy of Fallot Repair.
AB  - OBJECTIVE: After complete surgical repair the majority of tetralogy of Fallot
      (ToF), patients stay <=2 days in the Cardiac Intensive Care Unit (CICU) while
      some may stay longer. We undertook this study to investigate the factors
      associated with shorter vs. longer length of stay in the CICU to help manage
      resources effectively. DESIGN: Patients who underwent ToF repair at Aga Khan
      University, Pakistan, between July 2006 and December 2011 were studied in a case
      control design. Clinical parameters were compared between short stay group (SSG)
      (<=2 days) and long stay group (LSG) (>2 days). Odds ratios were calculated, and
      regression was performed. RESULTS: Ninety-eight patients (LSG 65, SSG 33) were
      included. Patients with lower preoperative saturation were 2.67 times more likely
      to be in the LSG group (P = .02). At 4 hours postoperatively, patients with a
      higher inotropic score (odds ratio [OR] = 3.03, confidence interval [CI] = 1.19
      7.7, P = .02), higher central venous pressure (OR = 3.04, CI = 1.27-7.32, P =
      .013), and significant tachycardia at 4 hours (OR = 3.5, CI = 1.19-10.3. P = .02)
      were at risk for having a prolonged CICU stay. On multivariate analysis,
      significant postoperative tachycardia at 4 hours (z-score >=3) was highly
      specific (sensitivity = 38.5%, specificity = 84.9%) for predicting the chances of
      being in the LSG. Other predictors included preop O(2) saturation <=82.5%
      (sensitivity = 61.1%, specificity = 63.0%) and CVP >=10 mm Hg at 4 hours
      (sensitivity = 55.4%, specificity = 71.9%). CONCLUSION: Patients who end up
      staying longer in the CICU have features that are distinctive in the immediate
      postoperative period, and this can help clinicians in identifying patients who
      may need more support.

PMID- 25864456
TI  - Making Sense of Dynamic Systems: How Our Understanding of Stocks and Flows
      Depends on a Global Perspective.
AB  - Stocks and flows (SF) are building blocks of dynamic systems: Stocks change
      through inflows and outflows, such as our bank balance changing with withdrawals
      and deposits, or atmospheric CO2 with absorptions and emissions. However, people
      make systematic errors when trying to infer the behavior of dynamic systems,
      termed SF failure, whose cognitive explanations are yet unknown. We argue that SF
      failure appears when people focus on specific system elements (local processing),
      rather than on the system structure and gestalt (global processing). Using a
      standard SF task (n = 148), SF failure decreased by (a) a global as opposed to
      local task format; (b) individual global as opposed to local processing styles;
      and (c) global as opposed to local perceptual priming. These results converge
      toward local processing as an explanation for SF failure. We discuss theoretical
      and practical implications on the connections between the scope of attention and
      understanding of dynamic systems. 

PMID- 25864455
TI  - Host cell heparan sulfate glycosaminoglycans are ligands for OspF-related
      proteins of the Lyme disease spirochete.
AB  - Borrelia burgdorferi, the agent of Lyme disease, spreads from the site of the
      tick bite to tissues such as heart, joints and the nervous tissues. Host
      glycosaminoglycans, highly modified repeating disaccharides that are present on
      cell surfaces and in extracellular matrix, are common targets of microbial
      pathogens during tissue colonization. While several dermatan sulfate-binding B.
      burgdorferi adhesins have been identified, B. burgdorferi adhesins documented to
      promote spirochetal binding to heparan sulfate have not yet been identified.
      OspEF-related proteins (Erps), a large family of plasmid-encoded surface
      lipoproteins that are produced in the mammalian host, can be divided into the
      OspF-related, OspEF-leader peptide (Elp) and OspE-related subfamilies. We show
      here that a member of the OspF-related subfamily, ErpG, binds to heparan sulfate
      and when produced on the surface of an otherwise non-adherent B. burgdorferi
      strain, ErpG promotes heparan sulfate-mediated bacterial attachment to the glial
      but not the endothelial, synovial or respiratory epithelial cells. Six other OspF
      related proteins were capable of binding heparan sulfate, whereas representative
      OspE-related and Elp proteins lacked this activity. These results indicate that
      OspF-related proteins are heparan sulfate-binding adhesins, at least one of which
      promotes bacterial attachment to glial cells.

PMID- 25864457
TI  - Health factors related to physical activity among children and adolescents:
      results from Spanish National Health Surveys 2006 and 2011/12.
AB  - PURPOSE: To describe the prevalence of physical activity during leisure time
      among children ages 6-14 in 2006 and 2011/12. DESIGN AND METHODS: A cross
      sectional study used individualized data for children 6-14 years of age from the
      Spanish National Health Surveys in 2006 (n = 5,108 children) and 2011/12 (n =
      3,265 children). RESULTS: Leisure time decreased between 2006 and 2011/12(p <
      .05). Variables associated with increased physical activity were: normal weight
      (odds ratio [OR] = 1.87; 95% confidence interval [CI]: 1.37-2.57), children
      perceived to be in good health by their parents (OR = 2.03;95% CI: 1.43-2.87),
      and less than 2 hr of screen time per day(OR = 2.00; 95% CI: 1.61-2.47). PRACTICE
      IMPLICATIONS: Primary care-based nurses are essential to improving adherence to
      physical activity.

PMID- 25864458
TI  - Treatment time, ease of use and cost associated with use of EquashieldTM,
      PhaSeal(r) , or no closed system transfer device for administration of cancer
      chemotherapy to a dog model.
AB  - This prospective experimental simulation study evaluated the efficiency, ease of
      use (EOU) and cost of administering chemotherapy with two closed system transfer
      devices (CSTD, EquashieldTM and PhaSeal(r) ) and no CSTD. Forty-six veterinary
      technicians (VT) working in oncology specialty practices were timed during
      chemotherapy administration simulated with water and a model canine limb 10 times
      with each system and with no CSTD. EOU and likelihood of recommending each system
      were rated by VT using visual analog scales. Costs were obtained from veterinary
      distributors. Administration was fastest with EquashieldTM (P = 0.0003), but the
      difference was not enough to affect case flow. EquashieldTM was easier to use
      than PhaSeal(r) or no CSTD (P = 0.002), however VT recommended both CSTD more
      strongly than no CSTD (P < 0.0001). EquashieldTM cost less than PhaSeal(r) but
      was sold only in bulk quantities. CSTD did not decrease efficiency in
      administering chemotherapy and were readily accepted by VT.

PMID- 25864459
TI  - Survival outcomes in patients with multiple primary melanomas.
AB  - BACKGROUND: A substantial number of melanoma patients will develop multiple
      primary melanomas (MPM). Currently, little is known about the impact of MPM on
      survival. OBJECTIVE: We aimed to determine whether melanoma survival is worse for
      patients with MPM compared to those with a single invasive primary melanoma
      (SPM). MATERIALS AND METHODS: A cohort study was conducted. Patients were sourced
      from an Australian population, with follow-up information collected
      retrospectively from registry data. Melanoma-specific survival analysis was
      performed to find associated variables after adjustment for known prognostic
      factors, using four different models, each selecting a different index melanoma
      lesion. RESULTS: 1068 stage I and II melanoma patients were followed up for a
      median of 24.4 years. MPM was found in 17.8% of the cohort (190 patients), more
      likely among males and older age groups. Other clinicopathological parameters
      were similar between the MPM and SPM (878 patients) cohorts. After adjustment for
      age, sex and Breslow thickness, MPM was a hazard for death from melanoma, across
      all models, reaching significance when considering the last invasive lesion as
      the index melanoma (HR = 2.76, P = 0.017). CONCLUSION: Patients with multiple
      invasive lesions seem more at risk of death from melanoma, independent of known
      prognostic factors.

PMID- 25864460
TI  - Diversification of the celiac disease alpha-gliadin complex in wheat: a 33-mer
      peptide with six overlapping epitopes, evolved following polyploidization.
AB  - The gluten proteins from wheat, barley and rye are responsible both for celiac
      disease (CD) and for non-celiac gluten sensitivity, two pathologies affecting up
      to 6-8% of the human population worldwide. The wheat alpha-gliadin proteins
      contain three major CD immunogenic peptides: p31-43, which induces the innate
      immune response; the 33-mer, formed by six overlapping copies of three highly
      stimulatory epitopes; and an additional DQ2.5-glia-alpha3 epitope which partially
      overlaps with the 33-mer. Next-generation sequencing (NGS) and Sanger sequencing
      of alpha-gliadin genes from diploid and polyploid wheat provided six types of
      alpha-gliadins (named 1-6) with strong differences in their frequencies in
      diploid and polyploid wheat, and in the presence and abundance of these CD
      immunogenic peptides. Immunogenic variants of the p31-43 peptide were found in
      most of the alpha-gliadins. Variants of the DQ2.5-glia-alpha3 epitope were
      associated with specific types of alpha-gliadins. Remarkably, only type 1 alpha
      gliadins contained 33-mer epitopes. Moreover, the full immunodominant 33-mer
      fragment was only present in hexaploid wheat at low abundance, probably as the
      result of allohexaploidization events from subtype 1.2 alpha-gliadins found only
      in Aegilops tauschii, the D-genome donor of hexaploid wheat. Type 3 alpha
      gliadins seem to be the ancestral type as they are found in most of the alpha
      gliadin-expressing Triticeae species. These findings are important for reducing
      the incidence of CD by the breeding/selection of wheat varieties with low
      stimulatory capacity of T cells. Moreover, advanced genome-editing techniques
      (TALENs, CRISPR) will be easier to implement on the small group of alpha-gliadins
      containing only immunogenic peptides.

PMID- 25864461
TI  - Role of mechanical compression on bone regeneration around a particulate bone
      graft material: an experimental study in rabbit calvaria.
AB  - PURPOSE: This experimental study was designed to analyze the effect of different
      compressive forces on the bone regeneration around a particulate bone graft
      material. MATERIAL AND METHODS: Eighty 6-mm-diameter defects were created in the
      calvaria of 20 New Zealand rabbits (4 defects per rabbit calvaria). All the
      defects were filled with particles of synthetic bone. Two standardized
      compressive forces were then applied, 4.1 g to half the defects (Test A) and 8.2
      g to the other half (Test B), all for 1 min. The graft sites were allowed to heal
      for 6 weeks, after which the rabbits were euthanized. The calvarium vault of each
      animal was extracted, radiographed, and prepared for histomorphometric analysis.
      The percentage of defect fill, bone density, new bone formation, and residual
      bone graft material were recorded, and the results were subjected to statistical
      analysis. RESULTS: Histological evaluation found that defect closure among the
      Test A (lower compression) group ranged from 38.34 (95% lower CI) to 55.8 (95%
      upper CI) (mean 47 +/- 8.5%), while among the Test B group (higher compression),
      it ranged from 81.26 (95% lower CI) to 95.32 (mean 88 +/- 7.3%). Significantly
      more closure was achieved for the Test B group (P < 0.05). Histomorphometric
      comparison of the two groups found significantly more new bone formation, higher
      bone density, and a higher percentage of defect fill in the defects subjected to
      the higher compression level (P < 0.05). CONCLUSIONS: Increasing the compressive
      force applied to bone graft particulate used to fill small defects created in
      rabbit calvaria appears to be beneficial.

PMID- 25864462
TI  - Incidental carcinoma of native kidneys in dialyzed and renal transplant patients:
      do we need new guidelines?

PMID- 25864463
TI  - Benefits of plasma rich in growth factors (PRGF) in skin photodamage: clinical
      response and histological assessment.
AB  - Skin ageing is characterized by small and fine wrinkles, roughness, laxity, and
      pigmentation as a result of epidermal thinning, collagen degradation, dermal
      atrophy, and fewer fibroblasts. Plasma rich in growth factors (PRGF) is an
      autologous plasma preparation enriched in proteins obtained from patient's own
      blood aimed at accelerating tissue repair and regeneration. To evaluate the
      benefits of PRGF in skin photodamage, 10 healthy volunteers were treated with
      three consecutive intradermal injections of PRGF in the facial area. Clinical
      outcomes and histological analysis were performed. A statistically significant
      increase in the epidermis and papillary dermis thickness was seen after PRGF
      treatment (p < 0.001). Skin thickening was observed in all patients studied,
      being more intense in the group of patients with photodamage (p < 0.001). After
      PRGF treatment, a reduction of the average area fraction of solar elastosis was
      observed in patients with clinical and histological signs of skin photodamage (p
      < 0.05).No changeswere observed in the number of CD31, XIIIa factor, cKit, CD10,
      nor p53-positive cells. The improvement score after PRGF use was 0.75 (9/12) for
      the group of patients with signs of skin photodamage. Intradermal PRGF
      infiltration appears to be an effective treatment for the photodamaged skin. 

PMID- 25864464
TI  - Prediction of metabolisable energy concentrations of fresh-cut grass using
      digestibility data measured with non-pregnant non-lactating cows.
AB  - Pasture-based ruminant production systems are common in certain areas of the
      world, but energy evaluation in grazing cattle is performed with equations
      developed, in their majority, with sheep or cattle fed total mixed rations. The
      aim of the current study was to develop predictions of metabolisable energy (ME)
      concentrations in fresh-cut grass offered to non-pregnant non-lactating cows at
      maintenance energy level, which may be more suitable for grazing cattle. Data
      were collected from three digestibility trials performed over consecutive grazing
      seasons. In order to cover a range of commercial conditions and data availability
      in pasture-based systems, thirty-eight equations for the prediction of energy
      concentrations and ratios were developed. An internal validation was performed
      for all equations and also for existing predictions of grass ME. Prediction error
      for ME using nutrient digestibility was lowest when gross energy (GE) or organic
      matter digestibilities were used as sole predictors, while the addition of grass
      nutrient contents reduced the difference between predicted and actual values, and
      explained more variation. Addition of N, GE and diethyl ether extract (EE)
      contents improved accuracy when digestible organic matter in DM was the primary
      predictor. When digestible energy was the primary explanatory variable,
      prediction error was relatively low, but addition of water-soluble carbohydrates,
      EE and acid-detergent fibre contents of grass decreased prediction error.
      Equations developed in the current study showed lower prediction errors when
      compared with those of existing equations, and may thus allow for an improved
      prediction of ME in practice, which is critical for the sustainability of pasture
      based systems. 

PMID- 25864465
TI  - Analysis of the Relative Contribution of Phagocytosis, LC3-Associated
      Phagocytosis, and Canonical Autophagy During Helicobacter pylori Infection of
      Macrophages.
AB  - BACKGROUND: Previous findings have suggested that Helicobacter pylori induces
      autophagic processes and subsequently takes refuge in autophagosomes, thereby
      contributing to persistent infection. Recently, a noncanonical form of autophagy,
      LC3 (microtubule-associated protein 1 light chain 3)-associated phagocytosis
      (LAP), has been shown to be required for efficient clearance of some
      intracellular bacteria. Whether H. pylori infection induces LAP had not been
      examined previously. In this study, we determined the extent to which H. pylori
      infection induces canonical autophagy or LAP in macrophages, and the involvement
      of the H. pylori cag pathogenicity island (cagPAI) with these processes. METHODS:
      Immunofluorescence confocal microscopy was used to analyze the formation of GFP
      LC3 puncta and their colocalization with H. pylori. Transmission electron
      microscopy was used to detect the ultrastructure of H. pylori-containing
      compartments. RESULTS: The majority of intracellular bacteria (85-95%) were found
      in phagosomes that were LC3-negative, with a small proportion (4-14%) appearing
      "free" in the cytosol. Only a very small percentage (0.5-6%) of intracellular H.
      pylori was sequestered in autophagosomes. Furthermore, no statistically
      significant difference in the relative distribution of H. pylori in the various
      compartments was observed between wild-type and cagPAI-mutant bacteria.
      CONCLUSIONS: In macrophages, H. pylori infection does not induce LAP, but can
      induce canonical autophagy, which entraps a very small fraction of intracellular
      bacteria. We propose that this subpopulation of intracellular H. pylori might
      have escaped from phagosomes into the cytosol before being sequestered by
      autophagosomes. The cagPAI of H. pylori has only minor influence, if any, on the
      extent of these processes.

PMID- 25864466
TI  - Environmental diversity as a surrogate for species representation.
AB  - Because many species have not been described and most species ranges have not
      been mapped, conservation planners often use surrogates for conservation
      planning, but evidence for surrogate effectiveness is weak. Surrogates are well
      mapped features such as soil types, landforms, occurrences of an easily observed
      taxon (discrete surrogates), and well-mapped environmental conditions (continuous
      surrogate). In the context of reserve selection, the idea is that a set of sites
      selected to span diversity in the surrogate will efficiently represent most
      species. Environmental diversity (ED) is a rarely used surrogate that selects
      sites to efficiently span multivariate ordination space. Because it selects
      across continuous environmental space, ED should perform better than discrete
      surrogates (which necessarily ignore within-bin and between-bin heterogeneity).
      Despite this theoretical advantage, ED appears to have performed poorly in
      previous tests of its ability to identify 50 * 50 km cells that represented
      vertebrates in Western Europe. Using an improved implementation of ED, we
      retested ED on Western European birds, mammals, reptiles, amphibians, and
      combined terrestrial vertebrates. We also tested ED on data sets for plants of
      Zimbabwe, birds of Spain, and birds of Arizona (United States). Sites selected
      using ED represented European mammals no better than randomly selected cells, but
      they represented species in the other 7 data sets with 20% to 84% effectiveness.
      This far exceeds the performance in previous tests of ED, and exceeds the
      performance of most discrete surrogates. We believe ED performed poorly in
      previous tests because those tests considered only a few candidate explanatory
      variables and used suboptimal forms of ED's selection algorithm. We suggest
      future work on ED focus on analyses at finer grain sizes more relevant to
      conservation decisions, explore the effect of selecting the explanatory variables
      most associated with species turnover, and investigate whether nonclimate abiotic
      variables can provide useful surrogates in an ED framework. 

PMID- 25864467
TI  - Reminiscences on the study of wind waves.
AB  - The wind blowing over sea surface generates tiny wind waves. They develop with
      time and space absorbing wind energy, and become huge wind waves usually referred
      to ocean surface waves. The wind waves cause not only serious sea disasters but
      also take important roles in the local and global climate changes by affecting
      the fluxes of momentum, heat and gases (e.g. CO2) through the air-sea boundary.
      The present paper reviews the selected studies on wind waves conducted by our
      group in the Research Institute for Applied Mechanics (RIAM), Kyushu University.
      The themes discussed are interactions between water waves and winds, the energy
      spectrum of wind waves, nonlinear properties of wind waves, and the effects of
      surfactant on some air-sea interaction phenomena. 

PMID- 25864469
TI  - Discovery of radioactive silver ((110m)Ag) in spiders and other fauna in the
      terrestrial environment after the meltdown of Fukushima Dai-ichi nuclear power
      plant.
AB  - Six months after the explosion of TEPCO's Fukushima Dai-ichi nuclear power plant,
      radioactive silver ((110m)Ag), was detected in concentrations of 3754 Bq/kg in
      Nephila clavata (the orb-web spider; Joro-gumo in Japanese) collected at
      Nimaibashi, Iitate village in Fukushima Prefecture, whereas (110m)Ag in the soil
      was 43.1 Bq/kg. A survey of 35 faunal species in the terrestrial environment
      during the 3.5 years after the accident showed that most of Anthropoda had two
      orders higher (110m)Ag in their tissues than soils, although silver is not an
      essential element for their life. However, tracing of the activity of (110m)Ag
      detected in spider Atypus karschi collected regularly at a fixed location showed
      that it declined much faster than the physical half-life. These results suggest
      that (110m)Ag was at once biologically concentrated by faunal species, especially
      Arthropoda, through food chain. The factors affecting the subsequent rapid
      decline of (110m)Ag concentration in faunal species are discussed. 

PMID- 25864470
TI  - A future with less HLA: potential clinical applications of HLA-universal cells.
AB  - The high variability of the human leukocyte antigen (HLA) remains a major
      obstacle to the application of allogeneic products in cell-based therapies. We
      have developed a strategy to decrease the immunogenicity of cell and tissues to
      improve their survival after allogeneic transplantation in the absence of
      immunosuppression. Using RNA interference technology, the expression of HLA class
      I and II was stably downregulated. HLA-silenced cells demonstrated to prevent a
      de novo and escape a pre-formed alloimmune response in vitro and in vivo. Also,
      they demonstrated to be capable of engraft and survive after allogeneic
      transplantation independently of the donor's and recipient's genetic background.
      The generation of HLA-universal cells has may open new horizons in the field of
      regenerative medicine. Some of the potential clinical applications of HLA
      universal cells will be discussed in this review.

PMID- 25864471
TI  - Paper-based inkjet-printed microfluidic analytical devices.
AB  - Rapid, precise, and reproducible deposition of a broad variety of functional
      materials, including analytical assay reagents and biomolecules, has made inkjet
      printing an effective tool for the fabrication of microanalytical devices. A
      ubiquitous office device as simple as a standard desktop printer with its
      multiple ink cartridges can be used for this purpose. This Review discusses the
      combination of inkjet printing technology with paper as a printing substrate for
      the fabrication of microfluidic paper-based analytical devices (MUPADs), which
      have developed into a fast-growing new field in analytical chemistry. After
      introducing the fundamentals of MUPADs and inkjet printing, it touches on topics
      such as the microfluidic patterning of paper, tailored arrangement of materials,
      and functionalities achievable exclusively by the inkjet deposition of analytical
      assay components, before concluding with an outlook on future perspectives. 

PMID- 25864472
TI  - Conceptions of mental health among Ugandan youth orphaned by AIDS.
AB  - The AIDS epidemic has disproportionately affected developing or low-income sub
      Saharan African countries. Within the context of the epidemic, children and youth
      are at risk of losing their parents at an early age. The experience of orphanhood
      due to AIDS has the potential to negatively impact on a child's mental health. A
      qualitative study was conducted to comprehensively describe the experience of
      orphanhood and its impact on mental health from the culturally specific
      perspective of Ugandan youths. We conducted interviews with a purposeful sample
      of 13 youths (ages 12 to 18) who had lost one or both parents to AIDS illness and
      who were also affiliated with a non-governmental organisation providing support
      to orphans. The orphaned youths experienced significant ongoing emotional
      difficulties following the death of their parent(s). The youths in this study
      were unfamiliar with the term 'mental health,' however they easily identified
      factors associated with good or poor mental health. In general, good mental
      health was associated with social conduct that is culturally appropriate. Poor
      mental health was perceived as a form of madness or insanity and it was
      associated with a loss of basic life necessities, such as access to food,
      education or shelter. The youths also identified factors that promote more
      successful orphans. The findings of this study suggest that Western terminologies
      and symptom constellations in the Diagnostic and Statistical Manual IV may not be
      applicable in an African cultural context. There are several clinical
      implications, including the development of a mental health intervention paradigm
      that emphasises resilience. 

PMID- 25864468
TI  - Hydrogen sulfide and polysulfides as signaling molecules.
AB  - Hydrogen sulfide (H2S) is a familiar toxic gas that smells of rotten eggs. After
      the identification of endogenous H2S in the mammalian brain two decades ago,
      studies of this molecule uncovered physiological roles in processes such as
      neuromodulation, vascular tone regulation, cytoprotection against oxidative
      stress, angiogenesis, anti-inflammation, and oxygen sensing. Enzymes that produce
      H2S, such as cystathionine beta-synthase, cystathionine gamma-lyase, and 3
      mercaptopyruvate sulfurtransferase have been studied intensively and well
      characterized. Polysulfides, which have a higher number of inner sulfur atoms
      than that in H2S, were recently identified as potential signaling molecules that
      can activate ion channels, transcription factors, and tumor suppressors with
      greater potency than that of H2S. This article focuses on our contribution to the
      discovery of these molecules and their metabolic pathways and mechanisms of
      action. 

PMID- 25864473
TI  - The phenomenology of bodily care: caregivers' experiences with AIDS patients
      before antiretroviral therapies in Lesotho.
AB  - This study provides an account of caregivers' experiences with the bodily care of
      AIDS patients before antiretroviral therapies were available in the public health
      sector in Lesotho. It describes the mechanisms through which the body may become
      a stressor in caregiving. The phenomenological method, guided by the notion of
      epoche, was used to understand caregiving experiences from the perspective of
      family caregivers. Data on caregivers' physical activities and what they saw and
      thought were collected through in-depth interviews with 21 caregivers (mostly
      females); the caregivers were identified with the help of HIV/AIDS counsellors at
      two hospitals where AIDS patients received medical treatment. The thematic
      analysis shows that a patient's body was central in caregiving experiences.
      Social interaction in caregiving was mediated through seeing and touching the
      bodies of the patients. The different aspects of caregiving and the close
      interaction with the body of an ill family member - especially seeing major
      changes in the patient's physical appearance, their declined capacity to perform
      the activities of daily living, and discovering the symptoms of their illness -
      contributed to the caregivers' experiences of sympathy and pain. The social
      meanings and boundaries that tended to persist regarding touching and accessing
      others' bodies and bodily matter also contributed to the caregivers' stress. 

PMID- 25864474
TI  - HIV behavioural surveillance among refugees and surrounding host communities in
      Uganda, 2006.
AB  - We used a standardised behavioural surveillance survey (BSS), modified to be
      directly relevant to populations in conflict and post-conflict settings as well
      as to their surrounding host populations, to survey the populations of a refugee
      settlement in south-western Uganda and its surrounding area. Two-stage
      probability sampling was used to conduct 800 interviews in each population. The
      BSS questionnaire adapted for displaced populations was administered to adults
      aged 15-59 years. It collected information on HIV knowledge, attitudes and
      practices; issues before, during and after displacement; level of interaction and
      sexual exploitation among the refugees and host communities (i.e., nationals).
      Population parameters were compared and 95% confidence intervals were calculated
      for core HIV indicators. The demographic characteristics were similar (except for
      educational achievement), and HIV awareness was very high (>95%) in both
      populations. The refugees reported more-accepting attitudes towards persons with
      HIV than did nationals (19% versus 13%; p < 0.01). More refugees than nationals
      reported ever having had transactional sex (10% versus 6%; p < 0.01), which
      mostly occurred post-displacement. Five percent of females among both the
      refugees and nationals reported experiencing forced sex, which mostly occurred
      post-displacement and after the arrival of refugees, respectively. Nationals
      reported more frequent travel to refugee settlements than reported by refugees to
      national villages (22% versus 11%; p < 0.01). The high mobility and frequent
      interactions of these two populations suggest that integrated HIV programmes
      should be developed and would be an efficient use of resources. Evidence
      suggesting that female refugees may be at elevated risk for HIV infection, due to
      forced sex, transactional sex and other vulnerabilities, warrants further
      examination through qualitative research. The findings indicate a need for
      additional, focused HIV-prevention programmes, such as youth education, for both
      refugees and Ugandan nationals. 

PMID- 25864475
TI  - Sex differentials in the use of centres for voluntary counselling and testing for
      HIV in Cameroon.
AB  - Part of the strategic response to HIV in Cameroon, West Africa, has been the
      institutionalisation of voluntary testing and counselling (VCT) for HIV services
      across the country. The study addresses the general level of awareness and use of
      VCT centres in Cameroon. The data were extracted from the national, cross
      sectional, 2004 Cameroon Demographic and Health Survey (DHS). The survey
      collected information on respondents' demographic characteristics and awareness
      and utilisation of VCT services, through a standard behavioural surveillance
      survey, administered in face-to-face interviews with males aged 15 years or older
      and females aged 15 to 49 years. Chi-square and logistic regression were employed
      for data analysis. A total of 5 280 males and 10 656 females responded to the
      2004 Cameroon DHS. More of the male than female respondents had a secondary or
      higher education (51.8% versus 39%), slightly more of the males than females
      resided in urban areas (57.3% versus 54.8%), and males were more likely than
      females to have heard of VCT centres (37.8% versus 26.8%) and were also much more
      likely to have had an HIV test at a VCT centre (5.9% males versus 1.3% females).
      The findings indicate that awareness and use of centres offering VCT for HIV is
      very low in Cameroon. Further research in Cameroon is needed to assess
      individuals' reasons for not using VCT, as well as studies to identify patterns
      of information flow regarding the dissemination of knowledge about HIV and AIDS
      and about VCT centres. 

PMID- 25864476
TI  - Couples' communication on sexual and relational issues among the Akamba in Kenya.
AB  - A large portion of HIV transmission in sub-Saharan Africa occurs among married
      couples, yet the majority of research on safer-sex communication has focused on
      communication between couples in casual relationships. This paper explores how
      committed Kamba couples in Machakos District, Kenya, communicate about sensitive
      relational issues. The findings from focus group discussions with five groups of
      males and five groups of females are presented. The couples freely shared their
      thoughts about daily and economic issues and certain aspects of family planning
      and sexuality. Methods for raising sensitive issues with partners included
      monitoring the spouse's mood, gradual or indirect revelation, mentioning topics
      during sex, and use of third-party intermediaries. Interference by extended
      family members, especially husbands' mothers, and male authoritarian roles
      emerged as hindrances to effective communication between couples. The
      implications for HIV prevention regarding gender differences and the role of
      families in couples' communication are discussed. 

PMID- 25864477
TI  - Facilitating health-enabling social contexts for youth: qualitative evaluation of
      a family-based HIV-prevention pilot programme.
AB  - This paper reports on a post-intervention qualitative evaluation of the pilot
      intervention of the AmaQhawe Family Project, in South Africa, which is a cartoon
      based, manualised intervention delivered to multiple family groups over 10
      sessions, aimed at preventing HIV in adolescents through strengthening the adult
      protective shield. Semi-structured interviews with nine women who had
      participated in the pilot intervention were used to understand participants'
      perceptions of how the family-based HIV-prevention programme had assisted in
      addressing the issues identified in a pre-intervention exploratory study.
      Analysis of the data was informed by community health psychology and social
      capital theory. The findings indicate that at an individual level, the women
      interviewed had experienced an improved sense of empowerment, both as parents and
      as women. They also reported increased social support for effective parenting. At
      a collective level, the women reported that the programme had helped them to
      exert better informal social controls within the community, as well as to
      increase their social leverage and participation in community organisations. The
      findings suggest that HIV interventions involving families can strengthen the
      adult protective shield to facilitate health-enabling social contexts for youth. 

PMID- 25864478
TI  - Sexual activity and condom use among people living with HIV in Swaziland.
AB  - A number of studies have shown strong evidence of the association between HIV
      testing and an increase in consistent condom use. These studies have shown that
      HIV testing has contributed to a reduction in risk behaviours, since knowledge of
      HIV status can motivate both HIV-positive and HIV-negative people to practise
      safer sex. However, the extent to which knowledge of one's HIV status contributes
      to behavioural change among people living with HIV (PLHIV) has not been
      comprehensively documented. Drawing on an analysis of 37 in-depth interviews and
      five focus group discussions with PLHIV, this paper examines the nature of sexual
      activity and condom use among PLHIV in Swaziland. The paper explores issues
      pertaining to behavioural change and safer sex, and how these are influenced by
      the individual's HIV-positive status and the prevailing social-structural forces.
      Several factors inhibit the adoption of protective sexual behaviour among HIV
      positive sexual partners, some of whom have access to life-saving drug therapy.
      These factors include a lack of adequate social support structures and prevailing
      gender power imbalances that deny women control over their sexual lives. To
      promote behavioural change among PLHIV, the paper proposes the expansion of the
      scope of information, education and communication strategies to include
      activities aimed at continually sensitising PLHIV regarding safer sex, as well as
      activities geared towards improving communication between PLHIV and their health
      caregivers with regard to HIV-protective behaviours. 

PMID- 25864479
TI  - 'Not only a teacher, but an ambassador': Facilitating HIV/AIDS educators to take
      action.
AB  - This article describes how South African educators were facilitated to adopt the
      role of HIV/AIDS 'ambassadors' within their circles of influence by participating
      in a two-year course for an Advanced Certificate in Education for HIV/AIDS in
      Teaching (ACE-HAT) qualification. It reports on the data generated by a
      qualitative study of the teachers' experiences with and subsequent to the
      programme. The programme works from the assumption that the HIV pandemic has
      provided us with an opportunity to address many of the issues and inequalities
      that the education system is facing today. Based on the Freirian notion of
      liberation pedagogy, the article puts forward the argument that by adopting a
      holistic and critical approach to HIV/AIDS education, educators are able to move
      beyond the traditional responsibilities of the teacher, and thus play an
      important role as agents of change in their school and community. 

PMID- 25864480
TI  - Assessment of HIV-positive in-patients using the International Classification of
      Functioning, Disability and Health (ICF) at Chris Hani Baragwanath Hospital,
      Johannesburg.
AB  - The International Classification of Functioning, Disability and Health (ICF)
      short-version checklist was used to assess the impairments, activity limitations
      and participation restrictions experienced by a sample of HIV-positive in
      patients admitted to Chris Hani Baragwanath Hospital in Johannesburg, South
      Africa. Laboratory tests, observation and review of patients' medical records
      were used to complete the ICF Checklist. Eighty patients were assessed (23 males
      and 57 females). Common impairments related to the following functions:
      digestive, metabolic and endocrine systems (83.9%); sensory (83.5%);
      haematological, immunological and respiratory systems (82.5%);
      neuromusculoskeletal movement (73.8%); mental (72.6%); energy and drive (75%);
      sleep (71%); emotional (62%); and muscle power (75%). Activity limitations were
      present in the area of mobility (56.4%), major life areas (55.1%), and community,
      social and civic life (50%). Associations found among impairments, activity
      limitations and participation restrictions were that patients with sensory
      problems were five-times more likely to have problems in self-care than people
      without sensory problems. Patients with impairments in the digestive,
      genitourinary and neuromusculoskeletal systems experienced problems with general
      tasks (confidence interval [CI]: 4.05-103.03; p < 0.01). Patients with
      cardiovascular, haematological, immunological and respiratory system problems
      were 14-times more likely to have problems with execution of general tasks (odds
      ratio [OR] 14.06, CI: 2.75-71.94; p = 0.002). Activities of participation
      restriction, difficulties with general tasks and demands (OR 9.68, CI: 1.20
      77.92), interpersonal relationships (OR 3.62, CI: 1.09-12.00), domestic life (OR
      3.97, CI: 1.12-14.16), and community, social and civic life (OR 4.13, CI: 1.05
      16.20) were closely associated with barriers in obtaining products for personal
      use and using technology. Understanding the prevalence and associations of
      disability and function in the course of HIV disease may serve as a baseline for
      developing appropriate and context-sensitive rehabilitation interventions and
      management strategies for people living with HIV or AIDS. 

PMID- 25864481
TI  - The economic burden of HIV and AIDS on households in Nigeria.
AB  - The study estimates the economic burden of HIV and AIDS on households in a
      Nigerian population. The data derive from a cross-sectional survey of households
      affected by HIV or AIDS in Ife-Ijesa Zone, Osun State, Nigeria. The sample
      consisted of 117 purposively selected, consenting adult HIV patients attending a
      general and teaching hospital. Participants were asked to self-report monetary
      expenses for HIV-related care, loss of savings, and funeral costs. The data show
      a significantly sharp drop in the participants' household income as a result of
      care for HIV-related illnesses, from the time of knowing one's HIV status to the
      time of illness, among three occupational categories (artisans, civil servants
      and unemployed; p = 0.02). Mean income among those in the unemployed category
      fell by 84.1%, income among artisans dropped by 72.6%, and income among civil
      servants decreased by 44.4%. The monetary loss during the course of HIV-related
      illnesses was heaviest for the artisan group, followed by the unemployed and the
      civil servants. Those who had lost a substantial part of their savings to HIV
      related care were most numerous among the unemployed, followed by artisans and
      civil servants. Out of 16 households, 11 (42.3%) had received support from
      relatives during a funeral ceremony. There was a significant association between
      the occupational group and working for more hours after illness (chi(2) = 9.28,
      df = 4; p = 0.05). Nearly all orphaned children were distributed to the extended
      family following the AIDS death of a parent. Among all the occupational groups,
      borrowing from a cooperative society during the course of HIV-related sickness
      was the commonest form. The findings add to data showing that despite the
      extended family support system, adult deaths due to AIDS continue to undermine
      the viability of sub-Saharan African households. 

PMID- 25864482
TI  - Appreciative inquiry into lifeskills-based HIV/AIDS education in South African
      schools.
AB  - With a steady rise in the prevalence of HIV and AIDS throughout the world it has
      become vital for programme implementers at all levels to ensure that all HIV
      intervention programmes are effectively put into practice. The present research
      used qualitative and quantitative data to evaluate the lifeskills-based HIV/AIDS
      education programme being implemented in primary and secondary schools in South
      Africa, with special reference to KwaZulu-Natal. A qualitative questionnaire
      gathered information from nine respondents at three levels: Department of
      Education district officials, educators and learners. Six key themes were
      consequently identified to guide the evaluation: communication, empowerment,
      resources, networking, motivation, and evaluation and feedback. A quantitative
      questionnaire completed by 30 educators revealed an overall positive attitude
      towards the programme, regardless of the educator's gender, age or level of
      formal education. The results are discussed with special reference to
      continuation and improvement of the lifeskills-based HIV/AIDS education
      programme. 

PMID- 25864483
TI  - Intimate Partner Violence Among Mothers of Sick Newborns in Ghana.
AB  - Intimate partner violence (IPV) is a major public health problem estimated to
      affect 15%-71% of women worldwide. We sought to elicit IPV risks among mothers of
      sick newborns in Ghana. As part of a broader study on postpartum depression, we
      conducted semistructured surveys of 153 women in a mother-baby unit, assessing
      demographics, depression, social support, and IPV with the present partner. Forty
      six percent of mothers reported some form of violence, mostly emotional (34%),
      followed by physical (17%), and sexual (15%). The study highlights the frequency
      of perinatal IPV and the associated risk factors of depression and poor social
      support. 

PMID- 25864484
TI  - Three-phase solvent systems for the comprehensive separation of a wide variety of
      compounds from Dicranostigma leptopodum by high-speed counter-current
      chromatography.
AB  - A three-phase solvent system was efficiently applied for high-speed counter
      current chromatography to separate secondary metabolites with a wide range of
      hydrophobicity in Dicranostigma leptopodum. The three-phase solvent system of n
      hexane/methyl tert-butyl ether/acetonitrile/0.5% triethylamine (2:2:3:2, v/v/v/v)
      was selected for high-speed counter-current chromatography separation. The
      separation was initiated by filling the column with a mixture of intermediate
      phase and lower phase as a stationary phase followed by elution with upper phase
      to separate the hydrophobic compounds. Then the mobile phase was switched to the
      intermediate phase to elute the moderately hydrophobic compounds, and finally the
      polar compounds still retained in the column were fractionated by eluting the
      column with the lower phase. In this research, 12 peaks were eluted out in one
      step operation within 110 min, among them, eight compounds with acceptable purity
      were obtained and identified. The purities of beta-sitosterol, protopine,
      allocryptopine, isocorydione, isocorydine, coptisine, berberrubine, and berberine
      were 94.7, 96.5, 97.9, 86.6, 98.9, 97.6, 95.7, and 92.8%, respectively. 

PMID- 25864485
TI  - A pH-induced, intein-mediated expression and purification of recombinant human
      epidermal growth factor in Escherichia coli.
AB  - Human epidermal growth factor (hEGF) is a cellular factor that promotes cell
      proliferation and has been widely used for the treatment of wounds, corneal
      injuries, and gastric ulcers. Recombinant hEGF (rhEGF) has previously been
      expressed using the pTWIN1 system with pH-induced intein and a chitin-binding
      domain. The rhEGF protein can be purified by chitin affinity chromatography
      because of the high affinity between the chitin-binding domain fusion-tag and the
      column. However, uncontrolled cleavage presents a major problem with this method.
      To overcome this problem, a novel purification method has been developed for a pH
      induced intein tag rhEGF that is expressed in Escherichia coli. Following
      purification by denaturation of inclusion bodies, the fusion protein is renatured
      and simultaneously induced to self-cleave by dialysis. Further purification of
      rhEGF is achieved by heat treatment and ion-exchange chromatography. Our results
      show that the purity of rhEGF obtained through this method is over 98% and the
      quantity of purified rhEGF is 248 mg from a 1 L culture or 2,967 mg from a 12 L
      culture. Therefore, we conclude that we have developed an efficient purification
      method of rhEGF, which may be used for the purification of other heat-resistant
      and acid-resistant recombinant proteins.

PMID- 25864486
TI  - Motor, affective and cognitive empathy in adolescence: Interrelations between
      facial electromyography and self-reported trait and state measures.
AB  - This study examined interrelations of trait and state empathy in an adolescent
      sample. Self-reported affective trait empathy and cognitive trait empathy were
      assessed during a home visit. During a test session at the university, motor
      empathy (facial electromyography), and self-reported affective and cognitive
      state empathy were assessed in response to empathy-inducing film clips portraying
      happiness and sadness. Adolescents who responded with stronger motor empathy
      consistently reported higher affective state empathy. Adolescents' motor empathy
      was also positively related to cognitive state empathy, either directly or
      indirectly via affective state empathy. Whereas trait empathy was consistently,
      but modestly, related to state empathy with sadness, for state empathy with
      happiness few trait-state associations were found. Together, the findings provide
      support for the notion that empathy is a multi-faceted phenomenon. Motor,
      affective and cognitive empathy seem to be related processes, each playing a
      different role in the ability to understand and share others' feelings. 

PMID- 25864487
TI  - Apremilast: a PDE4 inhibitor for the treatment of psoriatic arthritis.
AB  - INTRODUCTION: The evidence base for disease-modifying anti-rheumatic drugs used
      in psoriatic arthritis (PsA) is surprisingly weak, with most having little robust
      evidence to support their clinical use. Furthermore, there remain safety and
      tolerability concerns with both these and more recently available biological
      therapies. Apremilast , a novel, small molecule, represents the first oral
      therapy specifically developed for PsA. AREAS COVERED: This review describes the
      pharmacokinetic properties of apremilast and available data demonstrating
      significant benefits to both clinical and histological features of inflammatory
      arthritis. The key findings from a large Phase III clinical program will also be
      discussed, including short- and long-term efficacy outcomes and, importantly, the
      safety profile. Indications other than PsA will also be briefly reviewed. Given
      the recent nature of much of the data, published literature as well as
      information available only in the abstract format are included in this review.
      EXPERT OPINION: Studies show that treatment with apremilast results in
      significant improvement in both skin psoriasis and PsA symptoms. Apremilast has
      been approved by both the United States FDA and European Medicines Agency for
      treatment of PsA. Use of this medication is recommended in active PsA patients,
      according to local licensing.

PMID- 25864488
TI  - Genome-wide differentially methylated genes in prostate cancer tissues from
      African-American and Caucasian men.
AB  - Increasing evidence suggests that aberrant DNA methylation changes may contribute
      to prostate cancer (PCa) ethnic disparity. To comprehensively identify DNA
      methylation alterations in PCa disparity, we used the Illumina 450K methylation
      platform to interrogate the methylation status of 485,577 CpG sites focusing on
      gene-associated regions of the human genome. Genomic DNA from African-American
      (AA; 7 normal and 3 cancers) and Caucasian (Cau; 8 normal and 3 cancers) was used
      in the analysis. Hierarchical clustering analysis identified probe-sets unique to
      AA and Cau samples, as well as common to both. We selected 25 promoter-associated
      novel CpG sites most differentially methylated by race (fold change > 1.5-fold;
      adjusted P < 0.05) and compared the beta-value of these sites provided by the
      Illumina, Inc. array with quantitative methylation obtained by pyrosequencing in
      7 prostate cell lines. We found very good concordance of the methylation levels
      between beta-value and pyrosequencing. Gene expression analysis using qRT-PCR in
      a subset of 8 genes after treatment with 5-aza-2'-deoxycytidine and/or
      trichostatin showed up-regulation of gene expression in PCa cells. Quantitative
      analysis of 4 genes, SNRPN, SHANK2, MST1R, and ABCG5, in matched normal and PCa
      tissues derived from AA and Cau PCa patients demonstrated differential promoter
      methylation and concomitant differences in mRNA expression in prostate tissues
      from AA vs. Cau. Regression analysis in normal and PCa tissues as a function of
      race showed significantly higher methylation prevalence for SNRPN (P = 0.012),
      MST1R (P = 0.038), and ABCG5 (P < 0.0002) for AA vs. Cau samples. We selected the
      ABCG5 and SNRPN genes and verified their biological functions by Western blot
      analysis and siRNA gene knockout effects on cell proliferation and invasion in 4
      PCa cell lines (2 AA and 2 Cau patients-derived lines). Knockdown of either ABCG5
      or SNRPN resulted in a significant decrease in both invasion and proliferation in
      Cau PCa cell lines but we did not observe these remarkable loss-of-function
      effects in AA PCa cell lines. Our study demonstrates how differential genome-wide
      DNA methylation levels influence gene expression and biological functions in AA
      and Cau PCa. 

PMID- 25864489
TI  - Deconstructing the reactivation of imitation in young infants.
AB  - Reactivation is an automatic, perceptual process in which exposure to components
      of a forgotten event alleviates forgetting. Most research on infant memory
      reactivation has used conditioning paradigms. We used the puppet imitation task
      to systematically examine which stimuli could retrieve 6-month-olds' forgotten
      memory of the modeled actions. Infants watched an adult model a sequence of
      actions on a puppet, imitated the actions, and were exposed to reactivation cues
      24 hr before a 7-day (Experiment 1) or 14-day (Experiment 2) retention test.
      Exposure to any component of the original event reactivated the memory during the
      7-day test, but two of the same components failed to alleviate forgetting during
      the 14-day test. Increasing the number of retrieval cues facilitated 14-day test
      performance. These findings reveal that the principles of reactivation are the
      same for conditioning and imitation paradigms: The necessary and sufficient
      conditions for memory reactivation are directly related to memory accessibility.

PMID- 25864490
TI  - Delayed hypersensitivity to alpha-lipoic acid: look at dietary supplements.

PMID- 25864491
TI  - LP99: Discovery and Synthesis of the First Selective BRD7/9 Bromodomain
      Inhibitor.
AB  - The bromodomain-containing proteins BRD9 and BRD7 are part of the human SWI/SNF
      chromatin-remodeling complexes BAF and PBAF. To date, no selective inhibitor for
      BRD7/9 has been reported despite its potential value as a biological tool or as a
      lead for future therapeutics. The quinolone-fused lactam LP99 is now reported as
      the first potent and selective inhibitor of the BRD7 and BRD9 bromodomains.
      Development of LP99 from a fragment hit was expedited through balancing structure
      based inhibitor design and biophysical characterization against tractable
      chemical synthesis: Complexity-building nitro-Mannich/lactamization cascade
      processes allowed for early structure-activity relationship studies whereas an
      enantioselective organocatalytic nitro-Mannich reaction enabled the synthesis of
      the lead scaffold in enantioenriched form and on scale. This epigenetic probe was
      shown to inhibit the association of BRD7 and BRD9 to acetylated histones in vitro
      and in cells. Moreover, LP99 was used to demonstrate that BRD7/9 plays a role in
      regulating pro-inflammatory cytokine secretion. 

PMID- 25864497
TI  - Progress in equine surgery.

PMID- 25864492
TI  - Penetration Depth of Projectiles Fired from a Replica of Colt Navy of 1851 in 20%
      Gelatin Blocks Correlated with Fatal Injuries Assessed in an Autopsy of a 78-Year
      Old Man.
AB  - Pursuant to the Polish Weapons and Ammunitions Law, muzzle-loading black powder
      weapons, manufactured before 1885, or their replicas, as well as suitable
      projectiles, can be possessed legally without registration and special licenses.
      The aim of the study was to assess the penetration depth of projectiles fired
      from a black powder weapon, replica of Colt Navy of 1851, in 20% gelatin blocks
      and to compare the obtained results with the actual injuries found on autopsy of
      a 78-year-old man who had committed suicide. In the experiments, we used the
      black powder weapon and ammunitions, as well as gelatin blocks serving as a soft
      tissue model. We ascertained that solid spherical projectiles fired from black
      powder weapons cause extensive injuries, especially in the initial segment of the
      wound canal. Additionally, based on the presence and location of the wad in the
      wound canal, the distance from which the shot was fired can be determined. 

PMID- 25864499
TI  - Laryngoplasty in standing horses.
AB  - OBJECTIVE: To describe the clinical experience with standing laryngoplasty in a
      series of horses mostly nonracing. STUDY DESIGN: Case series. ANIMALS: Seventy
      one client-owned horses. METHODS: Medical records (April 2008-February 2014) of
      horses treated by standing laryngoplasty for abnormal respiratory noise and or
      poor performance were reviewed. Horses were included if they had a diagnosis of
      idiopathic right or left recurrent laryngeal neuropathy confirmed by
      videoendoscopy. All horses underwent a unilateral laryngoplasty with a unilateral
      or bilateral ventriculectomy or ventriculocordectomy. Follow-up endoscopy was
      performed in all horses within 24 hours postoperative, in 24 horses at 2-weeks,
      and in 65 horses at 6 weeks. Late follow-up was obtained from the trainer, owner,
      or referring veterinarian by telephone. RESULTS: Laryngoplasty was performed
      under endoscopic guidance with the horses sedated, and the surgical site was
      desensitized with local anesthetic solution. Laryngoplasty was completed in all
      horses and was well tolerated. No hyperabduction was observed. Two horses
      developed incisional swelling that resolved with drainage only. Late follow-up
      reported satisfactory improvement in respiration in all but 3 horses.
      CONCLUSIONS: Laryngoplasty performed with the horse standing avoids risks
      associated with general anesthesia and recovery and yields comparable results in
      nonracing horses, to laryngoplasty performed with the horse anesthetized. This
      technique reduces cost and allows accurate intraoperative adjustment of the
      degree of arytenoid abduction.

PMID- 25864500
TI  - The Validity of the Interpersonal Theory of Suicide in Adolescence: A Review.
AB  - Adolescence, when suicidal ideation and behaviors often begin, might offer an
      important window to understand the causes and prevent the progression of suicide
      phenomena. The need for frameworks to organize the fragmented field has been
      noted, but few studies are theoretically driven. An important recent contribution
      to understanding suicidality is Joiner's (2005) Interpersonal-Psychological
      Theory of Suicide (IPTS). This article reviews the evidence for the applicability
      of the IPTS in adolescence. Seventeen studies of adolescents that specifically
      tested or interpreted findings in the light of Joiner's theory or the IPTS were
      located. In addition, several recent reviews of the literature on suicidality in
      adolescence covered information relevant to the IPTS. There is some support for
      the theory in adolescence, particularly with regard to its most novel component,
      the association between acquired capability and suicide attempt. In summary, we
      find this theory to be a promising heuristic to organize the disparate studies in
      suicide research. Future challenges and directions for researchers seeking to
      test and elaborate the applicability of the IPTS in adolescence include:
      adaptations of instruments to the developmental stage, capturing of imminent
      risk, and consideration of whether the current model is underspecified. Age might
      moderate adult findings that give impulsivity an indirect role in suicide
      attempts.

PMID- 25864501
TI  - Metabolomic analysis reveals altered skeletal muscle amino acid and fatty acid
      handling in obese humans.
AB  - OBJECTIVE: Investigate the effects of obesity and high-fat diet (HFD) exposure on
      fatty acid oxidation and TCA cycle intermediates and amino acids in skeletal
      muscle to better characterize energy metabolism. METHODS: Plasma and skeletal
      muscle metabolomic profiles were measured from lean and obese males before and
      after a 5-day HFD in the 4 h postprandial condition. RESULTS: At both time
      points, plasma short-chain acylcarnitine species (SCAC) were higher in the obese
      subjects, while the amino acids glycine, histidine, methionine, and citrulline
      were lower in skeletal muscle of obese subjects. Skeletal muscle medium-chain
      acylcarnitines (MCAC) C6, C8, C10:2, C10:1, C10, and C12:1 increased in obese
      subjects, but decreased in lean subjects, from pre- to post-HFD. Plasma content
      of C10:1 was also decreased in the lean but increased in the obese subjects from
      pre- to post-HFD. CD36 increased from pre- to post-HFD in obese but not lean
      subjects. CONCLUSIONS: Lower skeletal muscle amino acid content and accumulation
      of plasma SCAC in obese subjects could reflect increased anaplerosis for TCA
      cycle intermediates, while accumulation of MCAC suggests limitations in beta
      oxidation. These measures may be important markers of or contributors to
      dysregulated metabolism observed in skeletal muscle of obese humans.

PMID- 25864503
TI  - Meta-analysis of risk factors for secondary traumatic stress in therapeutic work
      with trauma victims.
AB  - Revisions to the posttraumatic stress disorder (PTSD) diagnostic criteria in the
      fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM
      5; American Psychiatric Association, 2013) clarify that secondary exposure can
      lead to the development of impairing symptoms requiring treatment. Historically
      known as secondary traumatic stress (STS), this reaction occurs through
      repeatedly hearing the details of traumatic events experienced by others.
      Professionals who work therapeutically with trauma victims may be at particular
      risk for this exposure. This meta-analysis of 38 published studies examines 17
      risk factors for STS among professionals indirectly exposed to trauma through
      their therapeutic work with trauma victims. Small significant effect sizes were
      found for trauma caseload volume (r = .16), caseload frequency (r = .12),
      caseload ratio (r = .19), and having a personal trauma history (r = .19). Small
      negative effect sizes were found for work support (r = -.17) and social support
      (r = -.26). Demographic variables appear to be less implicated although more work
      is needed that examines the role of gender in the context of particular personal
      traumas. Caseload frequency and personal trauma effect sizes were moderated by
      year of publication. Future work should examine the measurement of STS and
      associated impairment, understudied risk factors, and effective interventions.

PMID- 25864502
TI  - Middle East respiratory syndrome: obstacles and prospects for vaccine
      development.
AB  - The recent emergence of Middle East respiratory syndrome (MERS) highlights the
      need to engineer new methods for expediting vaccine development against emerging
      diseases. However, several obstacles prevent pursuit of a licensable MERS
      vaccine. First, the lack of a suitable animal model for MERS complicates the in
      vivo testing of candidate vaccines. Second, due to the low number of MERS cases,
      pharmaceutical companies have little incentive to pursue MERS vaccine production
      as the costs of clinical trials are high. In addition, the timeline from bench
      research to approved vaccine use is 10 years or longer. Using novel methods and
      cost-saving strategies, genetically engineered vaccines can be produced quickly
      and cost-effectively. Along with progress in MERS animal model development, these
      obstacles can be circumvented or at least mitigated. 

PMID- 25864504
TI  - Trauma-related guilt: conceptual development and relationship with posttraumatic
      stress and depressive symptoms.
AB  - Despite high prevalence and concerning associated problems, little effort has
      been made to conceptualize the construct of posttraumatic guilt. This
      investigation examined the theoretical model of trauma-related guilt proposed by
      Kubany and Watson (2003). This model hypothesizes that emotional and physical
      distress related to trauma memories partially mediates the relationship between
      guilt cognitions and posttraumatic guilt. Using path analysis, this investigation
      (a) empirically evaluated relationships hypothesized in Kubany and Watson's
      model, and (b) extended this conceptualization by evaluating models whereby guilt
      cognitions, distress, and posttraumatic guilt were related to posttraumatic
      stress disorder (PTSD) symptoms depression symptom severity. Participants were
      male U.S. Iraq and Afghanistan veterans (N = 149). Results yielded a significant
      indirect effect from guilt cognitions to posttraumatic guilt via distress,
      providing support for Kubany and Watson's model (beta = .14). Findings suggested
      distress may be the strongest correlate of PTSD symptoms (beta = .47) and
      depression symptoms (beta = .40), and that guilt cognitions may serve to
      intensify the relationship between distress and posttraumatic psychopathology.
      Research is needed to evaluate whether distress specific to guilt cognitions
      operates differentially on posttraumatic guilt when compared to distress more
      broadly related to trauma memories.

PMID- 25864505
TI  - Ethical dilemmas, work-related guilt, and posttraumatic stress reactions of news
      journalists covering the terror attack in Norway in 2011.
AB  - News journalists working on crisis-related assignments may experience dilemmas
      with regard to how to conduct their work without causing additional harm to first
      hand victims. In this study, we investigated how exposure to journalistic ethical
      dilemmas during the Oslo/Utoya terror attack in 2011 and subsequent work-related
      guilt were related to the development of posttraumatic stress (PTS) reactions.
      Norwegian journalists (N = 371) covering the terror attack participated in a web
      based survey 8-9 months after the incident. We found that females reported more
      ethical dilemmas during the assignment than males (n = 356, d = 0.51). We also
      found that being on the scene was not related to more exposure to dilemmas (n =
      311, d = 0.01). Moreover, we discovered that work-related guilt had a significant
      indirect effect on the relationship between exposure to ethical dilemmas and
      severity of PTS reactions (n = 344, completely standardized indirect effect size
      = .11, 95% CI [.04, .19]. The results showed that exposure to ethical dilemmas
      may affect the development of long-term psychological impairment. We concluded
      that media organizations can prevent postcrisis impairment by preparing employees
      for possible exposure to dilemmas during crisis-related assignments.

PMID- 25864506
TI  - A preliminary study of an internet-based intervention for OEF/OIF veterans
      presenting for VA specialty PTSD care.
AB  - This preliminary study sought to evaluate the feasibility and potential
      effectiveness of a cognitive-behavioral, web-based intervention for posttraumatic
      stress in Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) veterans
      who are not able to participate, or not eligible to participate, in evidence
      based posttraumatic stress disorder (PTSD) treatments. The study used an
      uncontrolled pre-posttest design with a sample of 24 OEF/OIF veterans presenting
      to a VA PTSD specialty clinic. Participants used the afterdeployment.org, Post
      Traumatic Stress (PTS) Workshop, which was supplemented with brief weekly
      telephone calls. Half of the participants (n = 12) completed at least 5 of the 8
      workshop sessions. At posttreatment, 40.0% of completers demonstrated reliable
      reductions on PTSD symptoms and overall d = 1.04. Treatment satisfaction and
      acceptability was generally positive based on Likert ratings. This web-based
      intervention for PTS appears to be a feasible and potentially helpful
      intervention for veterans who may not otherwise receive psychosocial
      interventions. Given the minimal resources required and the potential reach, this
      web-based intervention could be a viable addition to services provided to OEF/OIF
      veterans seeking PTSD specialty care. Efforts to further develop and more
      rigorously evaluate this approach are warranted. 

PMID- 25864507
TI  - Why "monogamy" isn't good enough.
AB  - Rare in mammals but more common in primates, there remains a considerable
      controversy concerning whether primate species traditionally described as
      monogamous actually express this highly specialized breeding pattern.
      Unfortunately the definition of "monogamy" varies greatly, inhibiting our
      understanding of this trait and two related traits with which monogamy is often
      conflated: pair-living and pair-bonding. Strepsirrhine primates are useful models
      to study factors that select for pair-living, pair-bonding, and monogamy because
      this taxon exhibits high incidences of each trait, in addition to species that
      exhibit behaviors that reflect combinations of these traits. Several hypotheses
      have been articulated to help explain the evolution of "monogamy," but again,
      these hypotheses often conflate pair-living, pair-bonding, and/or monogamy. In
      this review, we (1) propose clear, discrete, and logical definitions for each
      trait; (2) review variation in strepsirrhines with respect to these three traits;
      (3) clarify which of these traits can be explained by existing hypotheses; and
      (4) provide an example of the applicability of the Resource Defense Hypothesis
      (RDH) to understand two of these traits, pair-living and pair-bonding, in the red
      bellied lemur (Eulemur rubriventer). Available data support the RDH for pair
      living in red-bellied lemurs. They live in stable family groups with one adult
      pair. Both sexes actively codefend territories that overlap little with other
      pairs' territories. Agonism is extremely rare within groups and intergroup and
      interspecific agonism varies with food availability. Available data also support
      the RDH for pair-bonding. Pair-bonds are cohesive year-round. Pairs coordinate
      behaviors to defend territories with auditory and olfactory signals. Cohesion
      increases with food abundance and both sexes reinforce bonds. We indicate where
      additional data will help to more rigorously test the RDH for each trait and
      encourage others to test alternative hypotheses.

PMID- 25864508
TI  - Roles of cofilin in development and its mechanisms of regulation.
AB  - Reorganization of the actin cytoskeleton is essential for cellular processes
      during animal development. Cofilin and actin depolymerizing factor (ADF) are
      potent actin-binding proteins that sever and depolymerize actin filaments, acting
      to generate the dynamics of the actin cytoskeleton. The activity of cofilin is
      spatially and temporally regulated by a variety of intracellular molecular
      mechanisms. Cofilin is regulated by cofilin binding molecules, is phosphorylated
      at Ser-3 (inactivation) by LIM-kinases (LIMKs) and testicular protein kinases
      (TESKs), and is dephosphorylated (reactivation) by slingshot protein phosphatases
      (SSHs). Although studies of the molecular mechanisms of cofilin-induced
      reorganization of the actin cytoskeleton have been ongoing for decades, the
      multicellular functions of cofilin and its regulation in development are just
      becoming apparent. This review describes the molecular mechanisms of generating
      actin dynamics by cofilin and the intracellular signaling pathways for regulating
      cofilin activity. Furthermore, recent findings of the roles of cofilin in the
      development of several tissues and organs, especially neural tissues and cells,
      in model animals are described. Recent developmental studies have indicated that
      cofilin and its regulatory mechanisms are involved in cellular proliferation and
      migration, the establishment of cellular polarity, and the dynamic regulation of
      organ morphology. 

PMID- 25864509
TI  - Pediatric Quality of Life while Supported with a Ventricular Assist Device.
AB  - OBJECTIVE: Ventricular assist devices (VADs) have emerged as an important
      treatment option for bridging pediatric patients with heart failure to
      transplant. VADs have shown improved survival; however, the pediatric quality of
      life (QoL) while on VAD support is unknown. We aimed to evaluate the QoL of our
      pediatric patients while supported with a VAD. DESIGN: In this prospective study,
      pediatric patients who underwent VAD placement, and their parents, were
      administered a generic Pediatric Quality of Life Inventory (PedsQL) 4.0 pre-VAD
      implant, when feasible, after the acute postoperative period, and then
      periodically until heart transplant or death. Their final scores while on support
      were compared with three previously reported groups: healthy controls,
      outpatients with severe heart disease, and children after heart transplant.
      RESULTS: From January 2008 to July 2014, 13 pediatric patients required VAD
      support greater than 2 weeks and completed a PedsQL. The mean age at implant was
      10.0 +/- 4.2 years and median duration of support was 1.6 (0.5-19.7) months.
      Eleven (85%) patients survived to transplant with one (8%) patient remaining
      alive on support. The median duration of support prior to their final PedsQL was
      1.4 (0.5-11.4) months. Patients self-reported significantly (P < .05) lower total
      and physical QoL scores when compared with all three comparison groups. Self
      reported psychosocial QoL scores were significantly lower than healthy controls
      only. Parent proxy-reported scores were significantly lower than all three
      comparison groups for all three categories (P < .05). CONCLUSIONS: A large
      deficit exists in the total QoL of pediatric patients supported by a VAD compared
      with outpatient management of severe heart disease or postheart transplant
      patients; however, VAD patients do represent a group with more severe heart
      failure. Improvements in QoL must be made, as time spent with a VAD will likely
      continue to increase.

PMID- 25864510
TI  - Removal of pathogenic bacterial biofilms by combinations of oxidizing compounds.
AB  - Bacterial biofilms are commonly formed on medical devices and food processing
      surfaces. The antimicrobials used have limited efficacy against the biofilms;
      therefore, new strategies to prevent and remove these structures are needed.
      Here, the effectiveness of brief oxidative treatments, based on the combination
      of sodium hypochlorite (NaClO) and hydrogen peroxide (H2O2) in the presence of
      copper sulfate (CuSO4), were evaluated against bacterial laboratory strains and
      clinical isolates, both in planktonic and biofilm states. Simultaneous
      application of oxidants synergistically inactivated planktonic cells and
      prevented biofilm formation of laboratory Escherichia coli, Salmonella enterica
      serovar Typhimurium, Klebsiella pneumoniae, and Staphylococcus aureus strains, as
      well as clinical isolates of Salmonella enterica subsp. enterica, Klebsiella
      oxytoca, and uropathogenic E. coli. In addition, preformed biofilms of E. coli C,
      Salmonella Typhimurium, K. pneumoniae, and Salmonella enterica exposed to
      treatments were removed by applying 12 mg/L NaClO, 0.1 mmol/L CuSO4, and 350
      mmol/L H2O2 for 5 min. Klebsiella oxytoca and Staphylococcus aureus required a 5
      fold increase in NaClO concentration, and the E. coli clinical isolate remained
      unremovable unless treatments were applied on biofilms formed within 24 h instead
      of 48 h. The application of treatments that last a few minutes using oxidizing
      compounds at low concentrations represents an interesting disinfection strategy
      against pathogens associated with medical and industrial settings. 

PMID- 25864511
TI  - Identification of human papillomavirus in pterygium.
AB  - PURPOSE: The purpose of this study was to evaluate the involvement of human
      papillomavirus in the pathogenesis of primary and recurrent pterygium in northern
      Israel. METHODS: A retrospective study examined 100 randomly chosen pterygium
      specimens with solar elastosis, from 100 patients who underwent pterygium surgery
      during 2012-2013 at the Emek Medical Center. All the specimens were analysed for
      evidence of human papillomavirus infection by immunohistochemistry. RESULTS:
      Human papillomavirus was not detected in any of the 100 pterygia samples by
      immunohistochemistry. These used samples were taken from 100 patients with mean
      age of 51.5 years and a primary: recurrent ratio of 8.09:1. CONCLUSION: We
      conclude from our study that human papillomavirus infection does not appear to be
      an important pathogenic factor of pterygium in Israel.

PMID- 25864512
TI  - Evaluation of the presence of reduced nicotinamide adenine dinucleotide phosphate
      in bacterial metabolites used as immunostimulators and its role in nitric oxide
      induction.
AB  - Bacterial metabolites that act as immunostimulators have aroused interest because
      of their therapeutic potential in several immune disorders. These metabolites are
      complex, heterogeneous, and comprise numerous immune-boosting biomolecules. To
      better understand their immune stimulatory properties, characterization of their
      components is essential. An ether extract of metabolites from nine bacterial
      species was analyzed for the presence of reduced nicotinamide adenine
      dinucleotide phosphate (NADPH) or other fluorophores. This metabolite in
      combination with bile lipids is a licensed immune stimulatory drug. Excitation of
      the extract at 340 nm resulted in fluorescence with an emission maximum of around
      410 nm, which is fairly specific for NADH and NADPH. Reverse-phase-HPLC and
      electro-spray ionization-mass analysis confirmed the presence of NADPH in the
      bacterial metabolites. Quantification by glutathione reductase assay indicated
      11.90 +/- 0.01 uM of NADPH in the metabolites. Further characterization of the
      individual bacterial extracts of the metabolite confirmed the presence of NADPH.
      Subsequently, studies were performed to evaluate the role/s of NADPH in immune
      stimulatory drugs. NADPH is known to be involved in production of nitric oxide
      (NO), which has versatile roles in the immune system. The biological function of
      NADPH in NO induction by RAW 264.7 (mouse macrophage) cells was evaluated and it
      was found that bacterial NADPH has a significant role in inducing NO and that
      NADPH from individual bacterial extracts is capable of inducing NO. Investigation
      on the stability and biological potency of NADPH in bacterial metabolites is
      important because of NADPH's wide therapeutic applications, most of which are
      associated with its role in NO induction.

PMID- 25864513
TI  - Ca2+ -independent sortase-A exhibits high selective protein ligation activity in
      the cytoplasm of Escherichia coli.
AB  - A Staphylococcus aureus transpeptidase, sortase A (SrtA), which catalyzes a
      peptide ligation with high substrate specificity, is a useful tool to site
      specifically attach proteinaceous/peptidic functional molecules to target
      proteins. However, its strong Ca(2+) dependency makes SrtA difficult for use
      under low Ca(2+) concentrations and in the presence of Ca(2+)-binding substances.
      To overcome this problem, we designed a SrtA mutant that Ca(2+)-independently
      demonstrates a high catalytic activity. The heptamutant
      (P94R/E105K/E108A/D160N/D165A/K190E/K196T), which resulted from a combination of
      known mutations at the Ca(2+) -binding site and around the substrate-binding
      site, successfully catalyzed a selective protein-protein ligation in the
      cytoplasm of Escherichia coli. Selective protein modification in living cells is
      a promising approach for investigating cellular events and regulating cell
      functions. This SrtA mutant may prove to be a versatile tool for adding new
      functionalities to proteins of interest by incorporating functional proteins and
      chemically modified peptides in living cells, which usually retain low Ca(2+)
      concentrations.

PMID- 25864514
TI  - Hedgehog signaling is activated in canine transitional cell carcinoma and
      contributes to cell proliferation and survival.
AB  - Transitional cell carcinoma (TCC) is the most commonly diagnosed tumor of the
      canine urinary system. Hedgehog (HH) signaling represents one possible novel
      therapeutic target, based on its recently identified central role in human
      urothelial carcinoma. The purpose of this study was to determine if HH mediators
      are expressed in canine TCC and the effect of inhibition of this pathway on cell
      growth and survival. HH pathway mediators were found to be expressed in five
      canine TCC cell lines. Indian HH was expressed in tumor cells in five canine
      bladder tumor tissues, but not in normal canine bladder tissue. Inhibition of HH
      signaling with cyclopamine and GANT61 led to significantly decreased cell
      proliferation but had a smaller effect on apoptosis. These results support future
      investigation of inhibitors of HH signaling in the treatment of canine TCC.

PMID- 25864515
TI  - 4D Printing with Mechanically Robust, Thermally Actuating Hydrogels.
AB  - A smart valve is created by 4D printing of hydrogels that are both mechanically
      robust and thermally actuating. The printed hydrogels are made up of an
      interpenetrating network of alginate and poly(N-isopropylacrylamide). 4D
      structures are created by printing the "dynamic" hydrogel ink alongside other
      static materials. 

PMID- 25864516
TI  - In reference to "Development, implementation, and impact of an automated early
      warning and response system for sepsis".

PMID- 25864517
TI  - Sympathetic neural activation does not mediate heart rate variability during
      repeated brief umbilical cord occlusions in near-term fetal sheep.
AB  - Changes in fetal heart rate variability (FHRV) and ST segment elevation (measured
      as the T/QRS ratio) are used to evaluate fetal adaptation to labour. The
      sympathetic nervous system (SNS) is an important contributor to FHRV under
      healthy normoxic conditions, and is critical for rapid support of blood pressure
      during brief labour-like asphyxia. However, although it has been assumed that SNS
      activity contributes to FHRV during labour; this has never been tested, and it is
      unclear whether the SNS contributes to the rapid increase in T/QRS ratio during
      brief asphyxia. Thirteen chronically instrumented fetal sheep at 0.85 of
      gestation received either chemical sympathectomy with 6-hydroxydopamine (6-OHDA;
      n = 6) or sham treatment (control; n = 7), followed 4-5 days later by 2 min
      episodes of complete umbilical cord occlusion repeated every 5 min for up to 4 h,
      or until mean arterial blood pressure fell to <20 mmHg for two successive
      occlusions. FHRV was decreased before occlusions in the 6-OHDA group (P < 0.05)
      and 2-4.5 h during recovery after occlusions (P < 0.05) compared to the control
      group. During each occlusion there was a rapid increase in T/QRS ratio. Between
      successive occlusions the T/QRS ratio rapidly returned to baseline, and FHRV
      increased above baseline in both groups (P < 0.05), with no significant effect of
      sympathectomy on FHRV or T/QRS ratio. In conclusion, these data show that SNS
      activity does not mediate the increase in FHRV between repeated episodes of brief
      umbilical cord occlusion or the transient increase in T/QRS ratio during
      occlusions.

PMID- 25864518
TI  - HES6 promotes prostate cancer aggressiveness independently of Notch signalling.
AB  - Notch signalling is implicated in the pathogenesis of a variety of cancers, but
      its role in prostate cancer is poorly understood. However, selected Notch pathway
      members are overrepresented in high-grade prostate cancers. We comprehensively
      profiled Notch pathway components in prostate cells and found prostate cancer
      specific up-regulation of NOTCH3 and HES6. Their expression was particularly high
      in androgen responsive lines. Up- and down-regulating Notch in these cells
      modulated expression of canonical Notch targets, HES1 and HEY1, which could also
      be induced by androgen. Surprisingly, androgen treatment also suppressed Notch
      receptor expression, suggesting that androgens can activate Notch target genes in
      a receptor-independent manner. Using a Notch-sensitive Recombination signal
      binding protein for immunoglobulin kappa J region (RBPJ) reporter assay, we found
      that basal levels of Notch signalling were significantly lower in prostate cancer
      cells compared to benign cells. Accordingly pharmacological Notch pathway
      blockade did not inhibit cancer cell growth or viability. In contrast to
      canonical Notch targets, HES6, a HES family member known to antagonize Notch
      signalling, was not regulated by Notch signalling, but relied instead on androgen
      levels, both in cultured cells and in human cancer tissues. When engineered into
      prostate cancer cells, reduced levels of HES6 resulted in reduced cancer cell
      invasion and clonogenic growth. By molecular profiling, we identified potential
      roles for HES6 in regulating hedgehog signalling, apoptosis and cell migration.
      Our results did not reveal any cell-autonomous roles for canonical Notch
      signalling in prostate cancer. However, the results do implicate HES6 as a
      promoter of prostate cancer progression. 

PMID- 25864520
TI  - Anisotropic particles templated by Janus emulsion.
AB  - Anisotropic particles, with morphology from crescent to moon shape and size from
      micrometer to nanometer scale, are fabricated in batch scale with Janus emulsion
      as template. The strategy is also useful in the synthesis of Janus particles with
      chemically distinct hemispheres. 

PMID- 25864519
TI  - Cytomegalovirus-induced thrombotic microangiopathy after renal transplant
      successfully treated with eculizumab: case report and review of the literature.
AB  - De novo thrombotic microangiopathy (TMA) after renal transplant is rare.
      Cytomegalovirus (CMV)-related post-transplant TMA has only been reported in 6
      cases. We report an unusual case of a 75-year-old woman who developed de novo TMA
      in association with CMV viremia. The recurrence of TMA with CMV viremia, the
      resolution with treatment for CMV, and the lack of correlation with a calcineurin
      inhibitor (CNI) in our case support CMV as the cause of the TMA. What is unique
      is that the use of eculizumab without plasmapheresis led to prompt improvement in
      renal function. After a failure to identify a genetic cause for TMA and the clear
      association with CMV, eculizumab was discontinued. This case provides insight
      into the pathogenesis and novel treatment of de novo TMA, highlights the
      beneficial effects of complement inhibitors in this disease, and shows that they
      can be safely discontinued once the inciting etiology is addressed. 

PMID- 25864521
TI  - Enhanced Suppression of Fertility Can be Achieved by Priming with FSHR and Eppin
      and Further Boosting with Their B-cell Epitope Peptides.
AB  - PROBLEM: In our previous study on adult male mice, we had identified one
      immunodominant epitope in hEppin and three epitopes in hFSHR that caused
      fertility inhibition. But it only demonstrated a moderate inhibitory effect on
      fertility, and the antifertility effect was unsatisfactory. METHOD OF STUDY:
      Based on the protein prime-peptide boost inoculation modalities, we further
      investigated whether the antifertility capacity could be enhanced by a combined
      immunization with the two antigens. RESULTS: The results displayed a enhanced
      suppressed fertility (F2EP2C 6.67%) in male mice similar to that seen after four
      separate administrations of the two proteins (F12E-4 5%). The most likely
      mechanism by which this antifertility efficacy was achieved was probably through
      the production of antibodies that led not only to impairment of spermatogenesis
      but also to inhibition of sperm motility. Moreover, this treatment also induced
      high concentrations of neutralizing antibodies which were secreted into the lumen
      of the epididymis. CONCLUSION: Thus, a combination immunization with hFSHR and
      hEppin enhanced the contraceptive effects and may provide a better means of
      immunocontraception.

PMID- 25864522
TI  - Dietary Intervention of Artemisia and Green Tea Extracts to Rejuvenate
      Helicobacter pylori-Associated Chronic Atrophic Gastritis and to Prevent
      Tumorigenesis.
AB  - OBJECT: As nonmicrobial dietary approach is capable of controlling Helicobacter
      pylori infection, we evaluated the efficacy of long-term dietary administration
      of Artemisia and/or green tea extracts on H. pylori-initiated, high-salt-promoted
      chronic atrophic gastritis and gastric tumorigenesis mouse model. METHODS:
      Helicobacter pylori-infected and high-salt-diet-administered C57BL/6 mice were
      administered with Artemisia extracts (MP group) and/or green tea extracts (GT
      group) for 36 weeks in addition to the control group (ES group, gastroprotective
      drug, ecabet sodium 30 mg/kg, diet pellet). Gross and pathological gastric
      lesions were evaluated after 24 and 36 weeks, respectively, and their underlying
      molecular changes were measured in gastric homogenates. Detailed mechanisms were
      further evaluated in in vitro cell models. RESULTS: The erythematous and nodular
      changes and mucosal ulcerative and erosive lesions were noted in the control
      group at 24 weeks. MP, GT, MPGT, and ES groups all showed significantly
      ameliorated pathologic lesion compared to the control group (p < .05). After the
      36 weeks, scattered nodular masses with some central ulcers and thin gastric
      surface were noted in the control stomach, whereas no tumorous lesion and milder
      atrophic changes were observed in all MP, GT, and MPGT groups except ES group (p
      < .05). On molecular analysis, increased expressions of COX-2, TNF-alpha, IL-6,
      lipid peroxide, and activated STAT3 relevant to H. pylori infection were
      significantly decreased with MPGT administration (p < .01), whereas HSP70 was
      significantly increased. PGDH expressions, core tumor suppressor involved in
      carcinogenesis, were significantly decreased with H. pylori infection (p < .05),
      but significantly increased in MPGT group (p < .05). Increased mucosal apoptotic
      index noted in the control group was significantly decreased with MP and/or GT
      along with significantly preserved gastric gastroprotective mediators (p < .01)
      such as mucins, HSP27, and HSP70. H. pylori-induced serum TNF-alpha and NF-kappaB
      activations were significantly decreased with MPGT administration (p < .05).
      CONCLUSION: Long-term dietary intake of MP and/or GT can be an effective strategy
      either to rejuvenate H. pylori atrophic gastritis or to suppress tumorigenesis.

PMID- 25864523
TI  - Marginal bone-level alterations of loaded zirconia and titanium dental implants:
      an experimental study in the dog mandible.
AB  - OBJECTIVES: The aim was to test whether or not the marginal bone-level
      alterations of loaded zirconia implants are similar to the bone-level alterations
      of a grade 4 titanium one-piece dental implant. MATERIALS AND METHODS: In six
      dogs, all premolars and the first molars were extracted in the mandible. Four
      months later, three zirconia implants (BPI, VC, ZD) and a control titanium one
      piece (STM) implant were randomly placed in each hemimandible and left for
      transmucosal healing (baseline). Six months later, CAD/CAM crowns were cemented.
      Sacrifice was scheduled at 6-month postloading. Digital X-rays were taken at
      implant placement, crowns insertion, and sacrifice. Marginal bone-level
      alterations were calculated, and intra- and intergroup comparisons performed
      adjusted by confounding factors. RESULTS: Implants were successfully placed.
      Until crown insertion, two implants were fractured (one VC, one ZD). At
      sacrifice, 5 more implants were (partly) fractured (one BPI, four ZD), and one
      lost osseointegration (VC). No decementation of crowns occurred. All implant
      systems demonstrated a statistically significant (except VC) loss of marginal
      bone between baseline and crown insertion ranging from 0.29 mm (VC; P = 0.116) to
      0.80 mm (ZD; P = 0.013). The estimated marginal bone loss between baseline and 6
      months of loading ranged between 0.19 mm (BPI) and 1.11 mm (VC), being
      statistically significant for STM and VC only (P < 0.05). The changes in marginal
      bone levels were statistically significantly different between zirconia implants
      and control implants (STM vs. BPI P = 0.007; vs. VC P = 0.001; vs. ZD P = 0.011).
      CONCLUSIONS: Zirconia implants were more prone to fracture prior to and after
      loading with implant-supported crowns compared to titanium implants. Individual
      differences and variability in the extent of the bone-level changes during the 12
      month study period were found between the different implant types and materials.

PMID- 25864524
TI  - Control of the breakup process of viscous droplets by an external electric field
      inside a microfluidic device.
AB  - Droplet-based microfluidic devices have received extensive attention in the
      fields of chemical synthesis, biochemical analysis, lab-on-chip devices, etc.
      Conventional passive microfluidic hydrodynamic flow-focusing devices (HFFDs)
      control the droplet breakup process by manipulating the flow ratios of the
      continuous phase to the dispersed phase. They confront difficulties in
      controlling droplet sizes in the dripping regime especially when the dispersed
      phase has a large viscosity. Previous studies have reported that an external
      electric field can be utilized as an additional tool to control the droplet
      breakup process in microfluidic devices. In this computational fluid dynamics
      (CFD) study, we have investigated the effect of an external static electric field
      on the droplet breakup process using the conservative level-set method coupled
      with the electrostatic model. The numerical simulations have demonstrated that
      the interaction of the electric field and the electric charges on the fluid
      interface induces the electric force, which plays a significant role in
      controlling the droplet formation dynamics. If the microfluidic system is applied
      with the electric field of varying strength, the droplet breakup process
      experiences three distinct regimes. In Regime 1, where low electric voltages are
      applied, the droplet size decreases almost linearly with the increase of voltage.
      Then the droplet size increases with the applied voltages in Regime 2, where the
      electric field has moderate strength. In Regime 3, where very large voltages are
      applied, the droplet size decreases with the applied voltage again. These
      interesting variations in the droplet breakup processes are explained by using
      transient pressure profiles in the dispersed phase and the continuous phase. The
      droplet breakup processes regulated by an external electric field that are
      revealed in this study can provide useful guidance on the design and operations
      of such droplet-based systems. 

PMID- 25864525
TI  - Bottom-up construction of triazine-based frameworks as metal-free
      electrocatalysts for oxygen reduction reaction.
AB  - A bottom-up method is used to construct novel metal-free catalysts for deeper
      study of oxygen reduction reaction (ORR) catalysis. Through controlling the
      structural evolution of a 2D covalent triazine-based framework, the conductivity,
      nitrogen configurations, and multidoping structures of the as-prepared catalysts
      can be easily tuned, which makes a great platform for both studying the
      mechanisms of the ORR and optimizing the performances of the metal-free
      catalysts. 

PMID- 25864526
TI  - Influence of double application technique on the bonding effectiveness of self
      etch adhesive systems.
AB  - AIM: To evaluate and compare the effect of double-application of single-step self
      etch adhesives using microleakage study and to analyze the dentin-adhesive
      interfacial micromorphology. METHODS: In total, 72 extracted human premolars were
      divided into three groups for different self-etch adhesives (G Bond, GC [GB],
      Optibond, Kerr [OB], and Xeno V Plus, Dentsply [XV]). Class V cavities were
      prepared. Each group was further divided into two subgroups (n = 10) according to
      the placement technique of the adhesive, using the single-application [subgroup
      (a)] or double-application method [subgroup (b)]. Resin composite (Z 250, 3M
      ESPE, St. Paul, MN) was used to restore the cavities and light cured for 40 s.
      Twenty samples from each group were subjected to microleakage study. Two samples
      from both the subgroups of the three adhesives were used for scanning electron
      microscopic examination of the resin-dentin interfacial ultrastructure. Dye
      leakage scores were subjected to statistical analysis using Kruskal-Wallis and
      Mann-Whitney U-tests at significance level of P < 0.05. RESULTS: GB depicted
      significantly more microleakage which was significantly greater than OB and XV.
      The double application led to significant decrease in microleakage of GB with no
      significant effect on the microleakage scores of other two all-in-one adhesives,
      that is OB and XV. CONCLUSION: Double application of all-in-one self-etch
      adhesives improves the marginal sealing ability in dentin although it appears to
      be product dependent.

PMID- 25864527
TI  - Low BMI is inversely associated with arterial stiffness in Africans.
AB  - In low socio-economic status communities in South Africa, African men showed a
      low BMI. Data on the effect of low BMI on cardiovascular function are scant. The
      present study aimed to assess the associations between low BMI and markers of
      cardiovascular function such as pulse wave velocity (PWV) and blood pressure in
      Africans aged 35-65 years, with low socio-economic status. The study population
      (n 496) was stratified into a low-BMI group with BMI <= 20 kg/m2 and a normal-BMI
      group with BMI >20 kg/m2 and <= 25 kg/m2. Blood pressure (Omron HEM-757) and PWV
      (Complior SP; Artech-Medical) was determined. Africans with low BMI showed an
      increased arterial stiffness with significantly higher PWV compared with the
      normal-BMI group (men: P= 0.001; women: P= 0.026), which remained after
      adjustment. In men with low BMI, PWV correlated negatively with BMI before (r 
      0.204; P= 0.012) and after (r -0.200; P= 0.020) adjustment. Forward stepwise
      regression analyses indicated a negative association between PWV and BMI in
      African men. A J-curve was evident suggesting a detrimental effect of low BMI on
      cardiovascular function in Africans. A low BMI may contribute to the high
      prevalence of cardiovascular-related morbidity and mortality within a developing
      country.

PMID- 25864528
TI  - Inheritance of field-relevant resistance to the Bacillus thuringiensis protein
      Cry1Ac in Pectinophora gossypiella (Lepidoptera: Gelechiidae) collected from
      India.
AB  - BACKGROUND: The inheritance and phenotypic expression of resistance to Bacillus
      thuringiensis Cry1Ac insecticidal protein were studied in selected populations of
      pink bollworm, Pectinophora gossypiella (Saunders), that were collected from
      Bollgard cotton in India. The individual populations in the pool were Cry1Ac
      resistant and sourced from Cry1Ac-containing Bt cotton (Bollgard) hybrids in
      2010. RESULTS: Laboratory selection on diet with 1.0 ug Cry1Ac protein mL(-1)
      increased the percentage reaching at least third instar from 7% in the F3
      generation to 94% in the F15 generation, a 257-fold increase in median lethal
      concentration relative to the susceptible strain. Analysis of reciprocal genetic
      crosses between the Cry1Ac-resistant strain NKJ and a susceptible laboratory
      strain MRC showed a dominance of 0.22, indicating that the inheritance of Cry1Ac
      resistance is partially recessive at Cry1Ac concentrations comparable with those
      in Bollgard. Analyses of backcrosses of F1 hybrid moths with NKJ and MRC
      indicated that resistance is autosomal. The Cry1Ac-resistant strain exhibited
      little or no cross-resistance to the Cry2Ab2 protein. CONCLUSION: This is the
      first study of the dominance of Cry1Ac field resistance in P. gossypiella. The
      results provide the basis for refining resistance management strategies for Bt
      cotton.

PMID- 25864529
TI  - The long history of the International Research Group in Immuno-Scintigraphy and
      Therapy (IRIST).

PMID- 25864530
TI  - Targeted ED-B fibronectin SPECT in vivo imaging in experimental atherosclerosis.
AB  - AIM: The extracellular matrix protein ED-B fibronectin (ED-B) is upregulated in
      inflammatory atherosclerotic lesions. However, functional in vivo imaging of ED-B
      containing plaques has not been explored. This study evaluated whether [(99m)Tc]
      conjugated AP39 ([(99m)Tc]-AP39), a single-chain antibody specific to ED-B, can
      be used for in vivo detection of atherosclerotic plaques in Western diet (WD)
      fed, apolipoprotein E-deficient (apoE-/-) mice as compared to wildtype (WT)
      control mice. METHODS: Using SPECT, 12-month-old WD-fed apoE-/- and WT mice were
      studied 4 hours after injecting [(99m)Tc]-AP39 (148 MBq). Subsequently, mice were
      sacrificed, thoracic aortas measured in a g-counter, and plaques analyzed using
      histology, immuno-histochemistry, autoradiography, and morphometry. RESULTS: In
      vivo [(99m)Tc]-AP39-SPECT imaging of apoE-/- mice demonstrated a significant
      signal activity in the plaque-ridden thoracic aorta (52.236 +/- 40.646 cpm/cm3)
      that co-localized with the aortic arch and the supra-aortic arteries in MRI
      scans. Low signal activity (9.468 +/- 4.976 cpm/cm3) was observed in WT mice. In
      apoE-/- mice, the strongest signals were detected in the aortic root, aortic arch
      and along the abdominal aorta. Autoradiography analysis of aortas from apoE-/-
      mice confirmed the in vivo observation by demonstrating signal localization in
      atherosclerotic plaques. The size of autoradiography-positive plaque areas
      correlated significantly with the size of ED-B-positive (r=0.645, P=0.044) or
      macrophage-infiltrated (r=0.84, P<0.002) plaques. A significant correlation was
      found between the sizes of ED-B-positive and macrophage-infiltrated plaque areas
      (r=0.93, P<0.01). CONCLUSION: [(99m)Tc]-AP39-SPECT in vivo imaging detects
      inflammatory plaque lesions in WD-fed apoE-/- mice.

PMID- 25864531
TI  - Impact of dental caries and its treatment on the quality of life of 12- to 15
      year-old adolescents in Benin, Nigeria.
AB  - AIM: To assess the impact of caries and its treatment on quality of life (QoL) in
      12- to 15-year-old children in Benin, Nigeria. DESIGN: This was a cross-sectional
      study involving 1790 children. Clinical examinations were conducted using the WHO
      criteria for diagnosis and coding of caries. The Decayed Missing Filled Teeth
      score of each child was calculated. The child Oral Impact on Daily Performance
      questionnaire was used to assess the QoL of children with caries pre- and post
      treatment. Associations between age, sex, and socio-economic status and caries
      were analysed using bivariate and multivariate logistic regression analysis.
      RESULTS: The prevalence of caries in the study population was 21.9%.
      Approximately 57% of children with caries reported negative impact on their QoL
      pre-treatment. Eating (47.6%) was the most affected domain. The mean pre
      treatment QoL score was 8.40 +/- 10.34. Four weeks post-treatment, only 1.12% of
      participants reported negative impact of caries treatment on their QoL. The mean
      post-treatment QoL score was 0.22 +/- 0.91 There was a significant difference
      between pre- and post-treatment QoL scores (P = 0.0001) with significant changes
      in all the eight domains studied. Age, sex, and socio-economic status had no
      significant impact on QoL pre- and post-treatment. CONCLUSIONS: Caries had a
      significant impact on the QoL of adolescents. Its treatment resulted in marked
      improvement in QoL.

PMID- 25864532
TI  - Ganglioside, disialosyl globopentaosylceramide (DSGb5), enhances the migration of
      renal cell carcinoma cells.
AB  - About one third of renal cell carcinoma (RCC) patients exhibit metastasis upon
      initial presentation. However, the molecular basis for RCC metastasis is not
      fully understood. A ganglioside, disialosyl globopentaosylceramide (DSGb5), was
      originally isolated from RCC tissue extracts, and its expression is correlated
      with RCC metastatic potential. DSGb5 is synthesized by GalNAc alpha2,6
      sialyltransferase VI (ST6GalNAcVI) and is expressed on the surface of RCC cells.
      Importantly, DSGb5 binds to sialic acid-binding Ig-like lectin-7 (Siglec-7)
      expressed on natural killer (NK) cells, thereby inhibiting NK-cell cytotoxicity.
      However, the role of DSGb5 in RCC progression remains obscure. To address this
      issue, we used ACHN cells derived from malignant pleural effusion of a patient
      with metastatic RCC. Using the limiting dilution method, we isolated three
      independent clones with different DSGb5 expression levels. Comparison of these
      clones indicated that the cloned cells with high DSGb5 expression levels
      exhibited greater migration potential, compared to the clone with low DSGb5
      expression levels. In contrast, DSGb5 expression levels exerted no significant
      effect on cell proliferation. We then established the ACHN-derived cell lines
      that stably expressed siRNA against ST6GalNAcVI mRNA or control siRNA.
      Importantly, the ST6GalNAcVI-knockdown cells expressed low levels of DSGb5. We
      thus demonstrated the significantly decreased migration potential of the
      ST6GalNAcVI-knockdown cells with low DSGb5 expression levels, compared to the
      control siRNA-transfected cells expressing high DSGb5 levels, but no significant
      difference in the cell proliferation. Thus, DSGb5 expression may ensure the
      migration of RCC cells. We propose that DSGb5 expressed on RCC cells may
      determine their metastatic capability. 

PMID- 25864533
TI  - Comprehensive cytotoxic evaluation of morin, a bioflavonoid against verapamil on
      rat gastrointestinal epithelium for novel pharmaceutical application involving P
      glycoprotein inhibition.
AB  - OBJECTIVE: In this study, a comprehensive and comparative cytotoxic evaluation of
      morin against verapamil on rat intestinal epithelium as P-gp inhibitors through
      in-vitro gastrointestinal short-term toxicity assays involving permeability
      studies for safety evaluation was investigated. METHODS: In this study, the
      effect of morin (1 mM or 10 mM) or verapamil (1 mM or 10 mM) or sodium
      deoxycholate (10 mM) was investigated on intestinal epithelium and isolated brush
      border membrane using biomarker assays. Cytotoxicity was determined using 3-(4,5
      dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay. The nutrients
      transport was assessed using everted sacs studies. Paracellular permeability was
      measured using Lucifer yellow, followed by morphometric analysis of intestinal
      sacs. KEY FINDINGS: Our results indicated that morin was effective in maintaining
      cell viability with no significant changes (P > 0.05) in the activity of
      intestinal brush border markers, membrane integrity and morphometric analysis as
      compared with control. On the contrary, dramatic (P < 0.01) changes were noticed
      in the release of membrane markers, cell viability and surface characteristics of
      intestinal segments when treated with verapamil or sodium deoxycholate as
      compared with control or morin. CONCLUSIONS: Our findings confirm that morin is
      non-toxic to rat intestinal epithelium against verapamil demonstrating the
      potential use of bioflavonoid as safe and novel pharmaceutical adjuvant as P-gp
      inhibitor.

PMID- 25864534
TI  - Magnetic Orderings in Li2Cu(WO4)2 with Tungstate-Bridged Quasi-1D Spin-1/2
      Chains.
AB  - By both experimental measurements and theoretical calculations, we investigated
      the magnetic and electronic properties of Li2Cu(WO4)2 as a tungstate-bridged
      quasi-one-dimensional (1D) copper spin-(1/2) chain system. Interestingly,
      magnetic susceptibility chi(T) and specific heat measurements show that the
      system undergoes a three-dimensional antiferromagnetic (AF)-like ordering at TN ~
      3.7 K, below a broad chi(T) maximum at ~8.9 K indicating a low-dimensional short
      range AF spin correlation. Bonner-Fisher model fitting of chi(T) leads to an AF
      intrachain exchange constant of J/kB = 15.8 +/- 0.1 K, and mean-field theory
      estimation gives an interchain coupling constant of J?/kB = 1.6 K, which supports
      the quasi-1D nature of this spin system. Theoretical evaluation of exchange
      coupling constants within the generalized gradient approximation (GGA) plus on
      site Coulomb interaction (U) shows that the dominant AF exchange interaction is
      of ~13.9 K along the a-axis with weak interchain coupling, in agreement with the
      experimental result of a quasi-1D spin-(1/2) chain system. The GGA+U calculations
      also predict that Li2Cu(WO4)2 is a charge transfer-type AF semiconductor with a
      direct band gap of 1.5 eV. 

PMID- 25864535
TI  - Stereoselective synthesis and reaction of gold(I) (Z)-enethiolates.
AB  - Bench-top-storable (Z)-enethiol reagents: gold (Z)-1-decenylthiolates were
      synthesized stereoselectively in high yields. They are stable upon storage at
      room temperature without protection from light, and react smoothly with various
      alkyl halides, alpha,beta-unsaturated ketones, and electron-deficient aryl
      halides with excellent stereoselectivity. 

PMID- 25864537
TI  - Assessing thermochemical properties of materials through ab initio quantum
      mechanical methods: the case of alpha-Al2O3.
AB  - The thermochemical behavior of alpha-Al2O3 corundum in the whole temperature
      range 0-2317 K (melting point) and under pressures up to 12 GPa is predicted by
      applying ab initio methods based on the density functional theory (DFT), the use
      of a local basis set and periodic-boundary conditions. Thermodynamic properties
      are treated both within and beyond the harmonic approximation to the lattice
      potential. In particular, a recent implementation of the quasi-harmonic
      approximation, in the Crystal program, is here shown to provide a reliable
      description of the thermal expansion coefficient, entropy, constant-volume and
      constant-pressure specific heats, and temperature dependence of the bulk modulus,
      nearly up to the corundum melting temperature. This is a remarkable outcome
      suggesting alpha-Al2O3 to be an almost perfect quasi-harmonic crystal. The effect
      of using different computational parameters and DFT functionals belonging to
      different levels of approximations on the accuracy of the thermal properties is
      tested, providing a reference for further studies involving alumina polymorphs
      and, more generally, quasi-ionic minerals. 

PMID- 25864536
TI  - Long-term subarachnoid haemorrhage survivors still die due to cerebrovascular
      causes.
AB  - OBJECTIVE: Subarachnoid haemorrhage (SAH) is associated with sympathetic nervous
      activation and inflammation. SAH could therefore theoretically be a risk factor
      for development of cardiovascular disease. The aim of this study was to
      investigate whether long-term (>=1 year) SAH survivors had an increased risk of
      death due to cardiovascular causes. MATERIAL & METHODS: SAH patients >=18 years
      treated at Umea University Hospital between 1986 and 2006 were eligible for
      inclusion. Deceased patients were identified in the Swedish population register.
      Death certificates from long-term SAH survivors and causes of death in the
      general population were obtained from the National Board of Health and Welfare,
      Sweden. The prevalence of comorbidities at the time of SAH was compared with the
      distribution of cardiovascular risk factors in the northern Sweden MONICA
      (Multinational Monitoring of Trends and Determinants in Cardiovascular Disease)
      health survey. Analyses were stratified for age and sex. RESULTS: In the SAH
      patients, the median year of SAH was 1992 and the median year of death was 2001.
      The MONICA survey in 1994 and the distribution of deaths in the general
      population in 2001 were used for comparison. Long-term SAH survivors had,
      compared to the general population, a significantly increased risk for death due
      to cerebrovascular disease (P < 0.0001), but not for death due to cardiovascular
      disease. Hypertension was more common in SAH patients compared to survey
      participants (P < 0.01). CONCLUSION: Cerebrovascular causes of death were
      significantly more common in long-term survivors after SAH compared to the
      general population.

PMID- 25864538
TI  - Spatial patterns of carbon, biodiversity, deforestation threat, and REDD+
      projects in Indonesia.
AB  - There are concerns that Reduced Emissions from Deforestation and forest
      Degradation (REDD+) may fail to deliver potential biodiversity cobenefits if it
      is focused on high carbon areas. We explored the spatial overlaps between carbon
      stocks, biodiversity, projected deforestation threats, and the location of REDD+
      projects in Indonesia, a tropical country at the forefront of REDD+ development.
      For biodiversity, we assembled data on the distribution of terrestrial
      vertebrates (ranges of amphibians, mammals, birds, reptiles) and plants (species
      distribution models for 8 families). We then investigated congruence between
      different measures of biodiversity richness and carbon stocks at the national and
      subnational scales. Finally, we mapped active REDD+ projects and investigated the
      carbon density and potential biodiversity richness and modeled deforestation
      pressures within these forests relative to protected areas and unprotected
      forests. There was little internal overlap among the different hotspots (richest
      10% of cells) of species richness. There was also no consistent spatial
      congruence between carbon stocks and the biodiversity measures: a weak negative
      correlation at the national scale masked highly variable and nonlinear
      relationships island by island. Current REDD+ projects were preferentially
      located in areas with higher total species richness and threatened species
      richness but lower carbon densities than protected areas and unprotected forests.
      Although a quarter of the total area of these REDD+ projects is under relatively
      high deforestation pressure, the majority of the REDD+ area is not. In Indonesia
      at least, first-generation REDD+ projects are located where they are likely to
      deliver biodiversity benefits. However, if REDD+ is to deliver additional gains
      for climate and biodiversity, projects will need to focus on forests with the
      highest threat to deforestation, which will have cost implications for future
      REDD+ implementation. 

PMID- 25864539
TI  - 2D Zeolite Coatings: Langmuir-Schaefer Deposition of 3 nm Thick MFI Zeolite
      Nanosheets.
AB  - Stable suspensions of zeolite nanosheets (3 nm thick MFI layers) were prepared in
      ethanol following acid treatment, which partially removed the associated organic
      structure-directing agent. Nanosheets from these suspensions could then be
      dispersed at the air-water interface and transferred to silicon wafers using
      Langmuir-Schaefer deposition. Using layer-by-layer deposition, control on coating
      thickness was demonstrated. In-plane X-ray diffraction (XRD) revealed that the
      deposited nanosheets contract upon calcination similar to bulk MFI crystals.
      Different methods for secondary growth resulted in preferentially oriented thin
      films of MFI, which had sub-12-nm thickness in certain cases. Upon calcination,
      there was no contraction detectable by in-plane XRD, indicating well-intergrown
      MFI films that are strongly attached to the substrate. 

PMID- 25864540
TI  - A network-level explanation for the differences in HIV prevalence in South
      Africa's racial groups.
AB  - Analyses of individual-level risk factors have not been able to adequately
      explain why HIV has spread so extensively in southern Africa and why this has
      occurred especially within certain racial or ethnic groups. Using data from a
      longitudinal study of a representative sample of adolescents aged 14-22 living in
      Cape Town, South Africa, this article presents evidence of how differences in
      individual-level risk factors as well as sexual network structures between
      different racial or ethnic groups may help explain the differential spread of HIV
      in South Africa. Particular emphasis is placed on how levels of partner
      concurrency, respondent concurrency, mutual concurrency, serial concurrency and
      numbers of sexual partners and an average early age of sexual debut combine in
      different ways in the different racial or ethnic groups to create networks of
      sexual partnerships that differ in the density of their interconnections and
      hence potential for HIV spread. These network-level differences offer a potential
      explanation for the observed generalised HIV epidemic seen among the population
      of black South Africans. 

PMID- 25864541
TI  - Factors associated with conception among a sample of HIV-positive women at a
      hospital in Uganda.
AB  - Conception among HIV-positive individuals is an important health and social
      issue. However, the proportion of HIV-positive women who conceive while being
      aware of their serostatus and the factors that influence this decision is not
      well documented. In a cross-sectional study, 385 HIV-positive women in the labour
      ward at Mulago Hospital, Uganda, were interviewed using a structured
      questionnaire. Data were collected on socio-demographic characteristics,
      contraception ever used, knowledge of antiretrovirals (ARVs), and ARVs ever used.
      To assess factors associated with conception among women who know their HIV
      positive status, the variables were compared for women in two groups: those who
      conceived while knowing their HIV-positive status and those who discovered their
      HIV status during pregnancy. Bivariate and logistic regression analyses were used
      to assess confounding variables and interactions. The data show that one in every
      three HIV-positive women in the study population (37.1%) conceived despite being
      HIV-positive. Women who conceived while knowing they were HIV-positive differed
      from those who conceived without knowing their HIV status in regard to employment
      status, marital status, the employment status of their spouse/partner, and their
      intention to conceive. Logistic regression showed that factors independently
      associated with conception in this sample of HIV-positive women were: age below
      25 years (odds ratio [OR] 2.06; 95% confidence interval [CI]: 1.18-3.62);
      unemployment (OR 2.7; 95% CI: 1.42-5.04); carrying a first pregnancy (OR 4.53;
      95% CI: 2.02-9.94), being unaware of her partner's HIV status (OR 0.26; 95% CI:
      0.15-0.44); having an awareness of ARVs (OR 3.66; 95% CI: 2.15-6.25); and having
      regrets about conceiving while being HIV-positive (OR 0.21; 95% CI: 0.09-0.46). 

PMID- 25864542
TI  - Diversity and mobility in households with children orphaned by AIDS in Couffo,
      Benin.
AB  - This paper characterises children orphaned by AIDS in the Couffo region of Benin.
      A 2006 census conducted for the research revealed a total of 315 such orphans,
      aged 0 to 14 years, within 88 households. Seventy-one percent of these children
      were under the care of their mothers or grandmothers, 68% were fatherless, 58%
      were between the ages of 7 and 12, and 68% were in primary school. An in-depth
      study of the orphans' lives, undertaken to complement the census, revealed that
      these orphans were highly mobile between households, with almost 50% of them
      moving homes within a six-month period. An analysis of this phenomenon found that
      orphan mobility was a deliberate household strategy to manage orphanhood.
      Tensions arising out of care arrangements and resource allocation were among the
      main reasons for the high degree of orphan mobility. The context of orphan
      mobility also highlighted the practical role the orphans were able to fulfil
      within the affected households. The findings show that orphan mobility is a
      social phenomenon with two functions: on one hand, it may help HIV/AIDS-affected
      households to manage the increase in the number of orphans; on the other, it can
      provide an opportunity for orphans to move to a 'safer' environment anytime they
      do not feel secure. The implications for institutions providing care to orphans
      were also identified. Among other things, we recommend that a distinction be made
      between the main caregiver and the 'endorser' of an orphan as this was found to
      be an important difference. We also recommended that a distinction be made
      between orphans under and over the age of 10. For instance, children in the age
      group 10-14 years should be defined as 'pre-adults,' as their position within the
      household and their needs for services are different from those of orphans under
      age 10. 

PMID- 25864543
TI  - Daniel arap Moi and the politics of HIV and AIDS in Kenya, 1983-2002.
AB  - The contrasting outcomes to HIV/AIDS prevention and mitigation processes in sub
      Saharan Africa have not been adequately investigated or explained. Specifically,
      few scholars have attempted to root the responses to HIV and AIDS within the
      socio-economic and political realities of those countries severely impacted by
      the disease. This article seeks to explain the ambivalent political response to
      HIV and AIDS in Kenya in the context of the neopatrimonial leadership of former
      president Daniel arap Moi, between 1983, when the disease was first identified,
      and 2002, when Moi finally left office. The article relies on rigorous
      interpretation and corroboration of secondary and primary data collected between
      2004 and 2006. The findings suggest that the slow and inadequate response to HIV
      and AIDS in Kenya during Moi's presidency was primarily dictated by the need to
      maintain the structures of his neopatrimonial leadership. 

PMID- 25864544
TI  - Recommendations for communication to enhance informed consent and enrolment at
      multilingual research sites.
AB  - Language issues can affect HIV and AIDS research trial enrolment, but little is
      understood about variables in this process. Some evidence indicates barriers
      exist even when the trial enrollers are linguistically and culturally matched to
      the participants and when consent forms are translated into a local language.
      Counsellors from two sites of an antiretroviral (ARV) drug trial in South Africa
      were trained to enrol patients using a modified process of informed consent. The
      outcomes of the standard and modified processes were subsequently compared in
      regard to accuracy of the patients' recall, aspects of the content and process,
      and evaluations made by the patients and counsellors. Marked differences were
      noted in the effectiveness of the enrolment process after the counsellors'
      training, as reflected in the potential participants' scores for comprehension
      and their evaluation comments. A flexible approach to seeking enrolment which
      harnesses natural strategies of interaction has the potential to improve the
      process of trial enrolment and informed consent, and decrease participants'
      anxiety and uncertainty. The findings have implications for methods of trial
      enrolment and specifically draw attention to the potential role of language
      specialists in research ethics committees and in trial designs and monitoring. 

PMID- 25864545
TI  - Religious participation and HIV-disclosure rationales among people living with
      HIV/AIDS in rural Swaziland.
AB  - Despite the cultural salience of Christianity in many parts of Africa and the
      expansion of antiretroviral treatment, few studies have examined experiences of
      religious participation among HIV-positive individuals. Correspondingly, most
      studies of HIV self-disclosure in sub-Saharan Africa focus primarily on
      disclosure to sexual partners. Addressing both concerns, the central concern of
      this article is HIV self-disclosure in church settings, where disclosure
      rationales functioned as a key heuristic to explore experience of HIV-positivity,
      religiosity, and church participation. Given 39.2% antenatal HIV prevalence in
      Swaziland-the highest in the world-and an estimated 6 500 local congregations,
      this article draws on a medical anthropological project in Swaziland to
      investigate experiences of church participation among HIV-positive individuals.
      The data were derived from semi-structured interviews with 28 HIV-positive
      individuals across three domains: 1) pre- and post-diagnosis religiosity; 2) HIV
      stigma and support in church settings; and 3) decisions around HIV disclosure.
      Field research and open-ended interviews with individuals close to people living
      with HIV, health personnel, and pastors provided important contextual data. A
      grounded theory analysis showed that HIV disclosure in church settings is a
      highly reflexive process, mediated by subjective religiosity, the social dynamics
      of church networks, and broader structural vulnerabilities. Church participation
      often entailed significant stigma, which negatively affected self-disclosure and
      help-seeking practices; however, a rhetoric of 'courage' emerged to describe
      individuals who voluntarily disclosed their HIV-positive status. Pastors and
      pastors' wives were key protagonists in disclosure strategies. A church-based
      defense of the meaning of personhood for people living with HIV was among the
      most important findings. Given that congregations in much of Africa are
      predominantly female, and because women comprised the majority of the sample, the
      study productively problematised church settings as sites of analysis where
      gender, poverty, and religion intersect disease epidemiology in ways that may
      have untapped programmatic implications. 

PMID- 25864546
TI  - Condom brands, perceptions of condom efficacy and HIV prevention among university
      students in KwaZulu-Natal, South Africa.
AB  - University students form an important constituency in interventions against HIV
      and AIDS. The majority of university students are between ages 18 and 30 years,
      which, according to recent surveys, is the age category at the highest risk of
      HIV infection. Even though there is currently no comprehensive statistical data
      on the HIV prevalence at South African institutions of higher learning, a number
      of studies have noted increasing AIDS-related deaths and sicknesses among
      students. This highlights the need for effective intervention against HIV
      infections within this community. Condom use remains the most effective
      intervention against HIV infection within sexually active populations. This paper
      examines perceptions of public-sector condoms and their impact on condom use
      among university students, based on the findings of research conducted at three
      universities in KwaZulu-Natal Province, South Africa. Study findings indicate
      that public-sector condoms are perceived as ineffective, smelly and even
      'infectious' and are widely seen to be of lower status as compared to the
      commercial brands. These perceptions were found to influence condom use as some
      students preferred to engage in unprotected sex rather than use public-sector
      condoms. The paper highlights the need for communication programmes to demystify
      the misconceptions surrounding public-sector condoms and to provide reassurance
      of the quality of such condoms. 

PMID- 25864547
TI  - Exploring the relationship between HIV and alcohol use in a remote Namibian
      mining community.
AB  - In southern Africa, the use of alcohol is increasingly seen as creating a context
      of risk for HIV transmission. This qualitative study investigates the links
      between alcohol use and higher-risk sexual behaviours in a remote southern
      Namibian mining-town community. Using data from six focus groups and 16 in-depth
      interviews conducted in 2008, the researchers investigated knowledge of the link
      between alcohol consumption and HIV risk, focusing on the specific mechanisms
      related to drinking and higher-risk sexual behaviours. Although knowledge
      regarding HIV and alcohol was high among the mineworkers and other community
      members, the social structure of a remote mining town appears to lead to high
      levels of alcohol use and higher-risk sexual behaviours. The heavy use of alcohol
      acts as an accelerant to these behaviours, including as a source of fortitude for
      those with an intention to engage in casual sexual partnerships or multiple
      concurrent partnerships, and as a cause for those behaviours for people who may
      otherwise intend to avoid them. The findings suggest a need for HIV-prevention
      programmes that focus more holistically on HIV and AIDS and alcohol use, as well
      as the need for structural changes to mining-town communities in order to reduce
      the likelihood of both heavy alcohol use as well as a high prevalence of higher
      risk sexual behaviours. 

PMID- 25864548
TI  - Public-private partnerships as a strategy against HIV/AIDS in South Africa: the
      influence of historical legacies.
AB  - In the face of the extreme challenges posed by the South African HIV/AIDS
      epidemic, collaboration between public and private partners is often called for
      in an attempt to mobilise additional resources and generate synergies. This paper
      shows that the ability to successfully use public-private partnerships to address
      complex challenges, such as an HIV/AIDS epidemic, is influenced by the fabric of
      society, one important aspect being historical legacies. The first part of the
      article shows how South Africa's apartheid past affects the ability of public and
      private partners to collaborate in a response to HIV and AIDS today. It also
      takes into account how reconciliation and nation-building policies in the
      immediate post-transformation period have affected the ability to form and
      sustain partnerships concerning HIV/AIDS issues. The second part of the article
      analyses more recent developments regarding the information that these hold as to
      the feasibility of public-private partnerships and whether these continue to be
      affected by the legacies of the past. Two events with symbolic political value in
      South Africa, namely the 2010 FIFA World Cup soccer event and the recent changes
      in government, are systematically examined on the basis of three analytical
      queries, regarding: the impact of the event on nation-building and transcending
      cleavages in society; the event's impact on the ability to form public-private
      partnerships in general; and the role of HIV/AIDS in connection with the event.
      Conclusions are drawn a propos the influence of historic factors on the ability
      of South African society to effectively use public-private partnerships in the
      response to HIV and AIDS, and the continued dynamics and likely future directions
      of these partnerships. 

PMID- 25864549
TI  - HIV-prevention knowledge among illiterate and low-literate women in rural Amhara,
      Ethiopia.
AB  - More than 85% of Ethiopia's population lives in rural areas and literacy levels
      in the country are relatively low. Despite this, little is known about levels of
      knowledge in regard to HIV/AIDS and condom use among illiterate and low-literate
      rural individuals. We conducted a cross-sectional study among 200 illiterate to
      semi-literate women, ages 13 to 24, from two rural communities in the Amhara
      region of northwestern Ethiopia. Nearly all the women had heard about HIV and
      AIDS. Among the illiterate individuals (n = 54), 24% did not know that HIV was
      the cause of AIDS and 48% did not know that HIV could be transmitted by sexual
      intercourse without a condom with an HIV-infected person. Among the same group,
      59% did not know what a condom is. Literacy had a strong positive association
      with knowledge of HIV transmission and condoms. Thus, due to a generally higher
      level of literacy (grade 5-8 attainment), very young women (ages 13-20) had
      better knowledge of HIV transmission and condoms than did women ages 21-24 who by
      comparison were less literate. Given poor knowledge of HIV transmission and
      condoms among illiterate and low-literate women in Amhara, targeted HIV
      prevention interventions are needed in this region. 

PMID- 25864550
TI  - Food consumption patterns, diversity of food nutrients and mean nutrient intake
      in relation to HIV/AIDS status in Kisumu district Kenya.
AB  - As the causes and consequences of the AIDS epidemic become clearer, so does the
      fundamental importance of food and nutritional security for HIV-affected
      individuals. Even as food insecurity remains a major problem in poor households,
      its effects are worsened in disease states like HIV infection. Food deficiency
      and nutritional inadequacy compromise an individual's physical status and work
      capacity, and may also diminish their resource base and household provisioning.
      The prevalence of HIV and AIDS in Kenya threatens food production systems, which
      intensifies poverty, increases the nutritional implications for HIV-infected
      individuals, accelerates the rate of orphanhood beyond what existing social
      networks can cope with, and basically affects all indicators of socio-economic
      development in the country. This cross-sectional study sought to assess food and
      nutrient intake in HIV-affected versus non-HIV-affected households. Purposive
      sampling was used to select 160 households (77 HIV-affected households and 83 non
      HIV-affected households) in Kisumu district, a lowland area along Lake Victoria.
      A consolidated questionnaire that included a food-frequency checklist and
      personal 24-hour dietary recall was used to gather information from 40
      households. The data were analysed quantitatively; descriptive statistics were
      mainly measures of central tendency, and inferential statistics involved chi
      square tests and independent t-test samples. A table depicting food composition
      was used to compute the nutrient intake of each household. The findings reveal a
      significant relationship between a household's HIV/AIDS status and nutrient
      intake. 

PMID- 25864551
TI  - Ethnographic experiences of HIV-positive nurses in managing stigma at a clinic in
      rural Uganda.
AB  - This paper explores the workplace experiences of HIV-positive nurses and their
      attempts to manage HIV/AIDS stigma. An HIV diagnosis can have a major impact on
      an individual's psychological and emotional wellbeing. Moreover, caring for those
      suffering from chronic HIV-related illnesses comes with additional stress, which
      makes providing care more complex. Stigma-reduction and assisting with
      psychosocial support and wellbeing is an integral part of ensuring that care
      providers who are HIV-positive have good outcomes both for themselves and their
      patients. An ethnographic study with HIV-positive nurses was conducted from
      August 2005 to December 2007 at a Health Centre IV HIV clinic in rural Luweero
      district, Uganda. Data were gathered through clinical participant observation,
      informal conversations, recorded life histories, open-ended in-depth interviews
      and topical focus group discussions. Nurses are in a position to help people
      through negative life events, yet they may personally experience the same types
      of negative life events. In the absence of a system to provide support for HIV
      and AIDS clinical care providers, a group of HIV-positive nurses initiated a
      support process by creating safe spaces for interacting and seeking psychosocial
      support among themselves in a relatively secretive way. This process provided the
      nurses with a solid foundation for developing interventions to assist them
      through difficult times. 

PMID- 25864552
TI  - Controlling defects in graphene for optimizing the electrical properties of
      graphene nanodevices.
AB  - Structural defects strongly impact the electrical transport properties of
      graphene nanostructures. In this Perspective, we give a brief overview of
      different types of defects in graphene and their effect on transport properties.
      We discuss recent experimental progress on graphene self-repair of defects, with
      a focus on in situ transmission electron microscopy studies. Finally, we present
      the outlook for graphene self-repair and in situ experiments. 

PMID- 25864553
TI  - Cotton-derived bulk and fiber aerogels grafted with nitrogen-doped graphene.
AB  - Three-dimensional graphene-based structures such as graphene aerogels or foams
      have shown applications in energy, environmental matters, and many other areas.
      Here, we present a method to convert raw cotton into functional aerogels
      containing a significant amount of nitrogen-doped graphene (N-graphene) sheets
      grafted on carbonized cellulose fibers. Urea was introduced into raw cotton as a
      molecular template as well as a nitrogen source to synthesize mushroom-like N
      graphene sheets strongly attached to cotton skeletons. The excellent
      processability of raw cotton allows us to configure bulk or meter-long fiber
      shaped aerogels, with high porosity and flexibility. Synergistic effects stemming
      from the integration of N-graphene and carbonized cotton skeletons promise
      potential applications as conductive electrodes for supercapacitors, with a
      measured specific capacitance of 107.5 F g(-1) in a two-electrode system. Our
      results indicate a low-cost and scalable approach toward high-performance
      graphene-based aerogels and electrodes via biomass templating. 

PMID- 25864554
TI  - Recalcitrant warts and topical cidofovir: predictive factors of good response.

PMID- 25864555
TI  - Punch biopsy vs. shave biopsy: a comparison of margin status of clinically
      atypical pigmented lesions.

PMID- 25864556
TI  - Automated analysis of filamentous microbial morphology with AnaMorf.
AB  - The morphological quantification of filamentous microbes represents an important
      analytical technique in the optimization of bioprocesses involving such
      organisms, given the demonstrated links between morphology and metabolite yield.
      However, in many studies, much of this quantification has required some degree of
      manual intervention, if it has been conducted at all, burdening biotechnologists
      with a time-consuming process and potentially introducing bias into analyses.
      Here, software for the automated quantification of filamentous microbes is
      presented, implemented as a plug-in for the widely used, freely available image
      analysis package, ImageJ. The software, together with all related source code,
      documentation and test data, is freely available to the community via an online
      repository.

PMID- 25864557
TI  - Protective effects of tanshinone IIA on myocardial ischemia reperfusion injury by
      reducing oxidative stress, HMGB1 expression, and inflammatory reaction.
AB  - CONTEXT: Although there were reports on the protective functions of tanshinone
      IIA (TSA) on rat myocardial ischemia, the exerting mechanism has not been
      completely clarified. OBJECTIVE: An attempt was made to further verify the
      protective effect of TSA on myocardial ischemia reperfusion injury and elucidate
      its underlying mechanism. MATERIALS AND METHODS: The rats were given TSA (10, 20,
      and 40 mg/kg bw per day) in intraperitoneal injection for 15 d. Rami anterior
      descending branch of coronary artery was ligated for 30 min and then re-perfused
      for 120 min to establish a reperfusion model. Effects of TSA on the infarct area,
      creatine kinase (CK), aspartate aminotransferase (AST), high mobility group box
      B1 protein (HMGB1), and inflammation and oxidation were investigated. RESULTS:
      Compared with those in the IR group, infarct size percentages of rats' myocardium
      in L-TSA, M-TSA, and H-TSA groups were reduced by 1.21, 4.26, and 12.50%,
      respectively, CK activities by 7.4, 11.2, and 12.5%, respectively, and AST
      activities also declined (p < 0.05). Furthermore, compared with those in the IR
      group, SOD and GSH-Px activities increased, and MDA, TNF-alpha, IL-6, and iNOS
      levels decreased in L-TSA, M-TSA, and H-TSA groups (p < 0.05). Meanwhile,
      compared with those in the IR group, HMGB1 expressions in L-TSA, M-TSA, and H-TSA
      groups were lowered by 21.9, 32.4, and 35.6%, respectively. DISCUSSION AND
      CONCLUSION: The protective function of TSA on myocardial ischemia reperfusion
      injury may be possibly exerted by inhibiting the increase of ROS caused by the
      reperfusion to attenuate the expression of HMGB1 and inhibit inflammation.

PMID- 25864558
TI  - Selective separation and determination of the synthetic colorants in beverages by
      magnetic solid-phase dispersion extraction based on a Fe3 O4 /reduced graphene
      oxide nanocomposite followed by high-performance liquid chromatography with diode
      array detection.
AB  - A facile adsorbent, a nanocomposite of Fe3 O4 and reduced graphene oxide, was
      fabricated for the selective separation and enrichment of synthetic aromatic azo
      colorants by magnetic solid-phase dispersion extraction. The nanocomposite was
      synthesized in a one-step reduction reaction and characterized by atomic force
      microscopy, scanning electron microscopy, Fourier transform infrared
      spectroscopy, Raman spectroscopy, X-ray diffraction and Brunauer-Emmett-Teller
      analysis. The colorants in beverages were quickly adsorbed onto the surface of
      the nanocomposite with strong pi-pi interactions between colorants and reduced
      graphene oxide, and separated with the assistance of an external magnetic field.
      Moreover, the four colorants in beverages were detected at different wavelengths
      by high performance liquid chromatography with diode array detection. A linear
      dependence of peak area was obtained over 0.05-10 MUg/mL with the limits of
      detection of 10.02, 11.90, 10.41, 15.91 ng/mL for tartrazine, allure red,
      amaranth, and new coccine, respectively (signal to noise = 3). The recoveries for
      the spiked colorants were in the range of 88.95-95.89% with the relative standard
      deviation less than 2.66%. The results indicated that the nanocomposite of Fe3 O4
      and reduced graphene oxide could be used as an excellent selective adsorbent for
      aromatic compounds and has potential applications in sample pretreatment. 

PMID- 25864559
TI  - Genome-wide sperm DNA methylation changes after 3 months of exercise training in
      humans.
AB  - AIM: DNA methylation programs gene expression and is involved in numerous
      biological processes. Accumulating evidence supports transgenerational
      inheritance of DNA methylation changes in mammals via germ cells. Our aim was to
      determine the effect of exercise on sperm DNA methylation. MATERIALS & METHODS:
      Twenty-four men were recruited and assigned to an exercise intervention or
      control group. Clinical parameters were measured and sperm samples were donated
      by subjects before and after the 3-month time-period. Mature sperm global and
      genome-wide DNA methylation was assessed using an ELISA assay and the 450K
      BeadChip (Illumina). RESULTS: Global and genome-wide sperm DNA methylation was
      altered after 3 months of exercise training. DNA methylation changes occurred in
      genes related to numerous diseases such as schizophrenia and Parkinson's disease.
      CONCLUSIONS: Our study provides the first evidence showing exercise training
      reprograms the sperm methylome. Whether these DNA methylation changes are
      inherited to future generations warrants attention.

PMID- 25864560
TI  - Sanofi's successful Phase 3 trials may lead to first-ever dengue vaccine in 2015.

PMID- 25864561
TI  - Developmental pathways of motor dysfunction.
AB  - Recent evidence has revealed unique patterns of behavioral development after
      prenatal insult similar to those outlined in studies of adult metabolic
      dysfunction after prenatal malnutrition. The hallmark features of this
      Developmental Pathway include a prenatal insult to the nervous system
      (environmental or genetic) followed by a period of Silent Vulnerability, where no
      or few functional deficits are observed, and finally emergence of later
      dysfunction. Possible mechanisms leading to later dysfunction from prenatal
      insult may include secondary or cascade effects due to the timing of prenatal
      insults relative to later developing structures in the brain. Methods best
      employed to study the mechanisms of these pathways are microgenetic and
      longitudinal designs that include behavioral assessment during the prenatal
      period of development, and animal models such as the guinea pig.

PMID- 25864562
TI  - meso-Hydroxysubporphyrins: A Cyclic Trimeric Assembly and a Stable meso-Oxy
      Radical.
AB  - Treatment of meso-chlorosubporphyrin with potassium hydroxide in DMSO followed by
      aqueous work up and recrystallization gave a cyclic trimer consisting of meso
      hydroxysubporphyrin units linked between the central boron atoms and meso-hydroxy
      groups. Solutions of this trimer are nonfluorescent, but become fluorescent when
      exposed to acid or base, since hydrolytic cleavage of the axial B-O bonds
      generates the meso-hydroxysubporphyrin monomer or its oxyanion. Ring cleavage of
      the trimer was also effected by reaction with phenylmagnesium bromide to produce
      meso-hydroxy-B-phenyl subporphyrin, which can be quantitatively oxidized with
      PbO2 to furnish a subporphyrin meso-oxy radical as a remarkably stable species as
      a result of spin delocalization over almost the entire molecule.

PMID- 25864563
TI  - The Relationship Between the Surface Morphology and Chemical Composition of
      Gunshot Residue Particles.
AB  - In this study, chemical composition and morphology of gunshot residue (GSR) of 9
      * 19 mm Parabellum-type MKE (Turkey)-brand ammunition were analyzed by scanning
      electron microscope and energy dispersive X-ray spectrometer. GSR samples were
      collected by "swab" technique from the shooter's right hand immediately after
      shooting. According to general principles of thermodynamics, it is likely that
      the structures will have a more regular (homogeneous) spherical form to minimize
      their surface area due to very high temperatures and pressures that occur during
      explosion. Studied samples were collected under the same conditions with the same
      original ammunition, from the same firearm and a single shooter. This is because
      many other variables may affect size, structure, and composition in addition to
      the concentrations of elements of the structure. Results indicated that the
      chemical compositions are effective in the formation of GSR morphological
      structures. 

PMID- 25864565
TI  - Varied Patterns of Family Resilience in Challenging Contexts.
AB  - While we know much about patterns of family resilience, most of our research and
      clinical discussion has focused on microsystemic, intrafamilial protective
      processes. We have far fewer maps of the bidirectional interactions between
      families and other systems that contribute to successful family adaptation in
      challenging contexts. The purpose of this article is to address this gap in
      knowledge and present a map of family resilience that is both systemic and
      contextually and culturally responsive. Seven specific patterns of family
      resilience are reviewed. Combined, they account for the varied adaptational
      patterns families use to nurture and sustain resilience. The article concludes
      with reflection on how we can assess family resilience and the application of
      this map to family therapy.

PMID- 25864564
TI  - Protective Role of Smad6 in Inflammation-Induced Valvular Cell Calcification.
AB  - Calcific aortic vascular and valvular disease (CAVD) is associated with
      hyperlipidemia, the effects of which occur through chronic inflammation. Evidence
      suggests that inhibitory small mothers against decapentaplegic (I-Smads; Smad6
      and 7) regulate valve embryogenesis and may serve as a mitigating factor in CAVD.
      However, whether I-Smads regulate inflammation-induced calcific vasculopathy is
      not clear. Therefore, we investigated the role of I-Smads in atherosclerotic
      calcification. Results showed that expression of Smad6, but not Smad7, was
      reduced in aortic and valve tissues of hyperlipidemic compared with normolipemic
      mice, while expression of tumor necrosis factor alpha (TNF-alpha) was
      upregulated. To test whether the effects are in response to inflammatory
      cytokines, we isolated murine aortic valve leaflets and cultured valvular
      interstitial cells (mVIC) from the normolipemic mice. By immunochemistry, mVICs
      were strongly positive for vimentin, weakly positive for smooth muscle alpha
      actin, and negative for an endothelial cell marker. TNF-alpha upregulated
      alkaline phosphatase (ALP) activity and matrix mineralization in mVICs. By gene
      expression analysis, TNF-alpha significantly upregulated bone morphogenetic
      protein 2 (BMP-2) expression while downregulating Smad6 expression. Smad7
      expression was not significantly affected. To further test the role of Smad6 on
      TNF-alpha-induced valvular cell calcification, we knocked down Smad6 expression
      using lentiviral transfection. In cells transfected with Smad6 shRNA, TNF-alpha
      further augmented ALP activity, expression of BMP-2, Wnt- and redox-regulated
      genes, and matrix mineralization compared with the control cells. These findings
      suggest that TNF-alpha induces valvular and vascular cell calcification, in part,
      by specifically reducing the expression of a BMP-2 signaling inhibitor, Smad6.

PMID- 25864566
TI  - The scientific legacy of Little Hans and Little Albert: future directions for
      research on specific phobias in youth.
AB  - We review issues associated with the phenomenology, etiology, assessment, and
      treatment of specific phobias in children and adolescents and provide suggestions
      for future research and clinical practice. In doing so, we highlight the early
      case studies of Little Hans and Little Albert and the advances that have been
      made following the publication of these seminal cases. In recent years, we have
      witnessed a deeper understanding of the etiology of specific phobias and
      developed a rich array of evidence-based assessments and treatments with which to
      address specific phobias in youth. Although much has been accomplished in this
      area of inquiry, we also note that much remains to be done before we can advance
      more fully our understanding, assessment, and treatment of specific phobias in
      youth. It will be important for future work to build more firmly on these
      developments and to better determine the moderators and mediators of change with
      our evidence-based treatments and to more vigorously pursue their dissemination
      in real-word settings. 

PMID- 25864567
TI  - Second-hand eating? Maternal perception of the food environment affects
      reproductive investment in mice.
AB  - OBJECTIVE: Little information exists on how perception of the food (or
      "energetic") environment affects body composition and reproductive investment.
      The hypothesis was tested that female mice, who are themselves consuming standard
      chow diets but who are exposed to conspecifics eating a rich "cafeteria diet,"
      will exhibit altered weight gain and reproductive investment. METHODS: Female
      C57BL/6 mice were raised on a cafeteria diet. At maturity, subjects were switched
      to a standard chow diet, and their cage-mates were assigned to consume either a
      cafeteria diet (treatment, n = 20) or standard chow (control, n = 20). Subjects
      were mated and pups raised to weaning. Subjects and pups were analyzed for body
      composition. RESULTS: Treatment had no discernable effect on dam body weight or
      composition but caused pups to have lower body weight (P = 0.036) and less fat
      mass (P = 0.041). A nearly significant treatment effect on "time to successful
      reproduction" (avg. 55 versus 44 days), likely due to increased failed first
      pregnancies, (14/19 versus 8/19, P = 0.099) was found. CONCLUSIONS: These data
      indicate that perceived food environment (independent of the diet actually
      consumed) can produce small pups with less body fat and possibly induce
      difficulties in pregnancy for dams. Replication and mechanistic studies should
      follow.

PMID- 25864568
TI  - Relationship between levator ani and bony pelvis morphology and clinical grade of
      prolapse in women.
AB  - The aim of this study was to assess the morphological features of the levator ani
      and bony pelvis in women with different grades of prolapse. Ninety Chinese women
      with different grades of uterine prolapse were studied, 18 in each stage of
      prolapse from I to IV, and 18 asymptomatic nulliparous volunteers as normal
      controls. Three-dimensional (3D) models that included the pelvic bones, levator
      ani, pubic symphysis, sacrum, and coccyx were generated from magnetic resonance
      (MR) images. The width and length of the levator hiatus and levator symphysis
      gap, the width of the iliococcygeus, and the iliococcygeal angle were measured to
      quantify levator ani morphology; the intertuberous diameter, interspinous
      diameter, subpubic angle, and pubococcygeal line were measured to characterize
      the morphology of the bony pelvis. Four patterns of levator ani morphology among
      women with and without prolapse were distinguished. Among the bony pelvis
      parameters, no measurement differed significantly between the subjects with
      prolapse and normal controls, or among subjects with different grades of
      prolapse. There were significant differences in the width and length of the
      levator hiatus and levator symphysis gap between women with prolapse and normal
      controls. Our pilot data help to elucidate bony pelvis and levator ani morphology
      in women with and without pelvic organ prolapse. In contrast to the iliococcygeus
      muscle, changes in the morphological features of the pubovisceral muscle are more
      likely to accompany prolapse.

PMID- 25864570
TI  - Hippocampal antioxidative system in mesial temporal lobe epilepsy.
AB  - OBJECTIVE: To examine antioxidative system in hippocampi of patients with mesial
      temporal lobe epilepsy associated with hippocampal sclerosis (mTLE-HS). METHODS:
      Activity and levels of antioxidative enzymes-catalase (CAT), glutathione
      peroxidase (GPx), glutathione reductase (GR), manganese superoxide dismutase
      (MnSOD), and copper-zinc superoxide dismutase (CuZnSOD)-were assessed in
      hippocampi of nine pharmacoresistant mTLE-HS patients (mean age 37.7 +/-
      [standard deviation] 6.6 years) who underwent amygdalohippocampectomy, and in 10
      hippocampi obtained via autopsy from five neurologically intact controls (mean
      age 34.4 +/- 9.0 years). Subfield and cellular (neuron/astrocyte) distribution of
      CAT, GPx, and MnSOD was analyzed in detail using immunohistochemical staining.
      RESULTS: Sclerotic hippocampi showed drastically increased activity of hydrogen
      peroxide-removing enzymes, CAT (p < 0.001), GPx (p < 0.001), and GR (p < 0.001),
      and significantly higher protein levels of CAT (p = 0.006), GPx (p = 0.040), GR
      (p = 0.024), and MnSOD (p = 0.004), compared to controls. CAT immunofluorescence
      was located mainly in neurons in both controls and HS. Control hippocampi showed
      GPx staining in blood vessels and CA neurons. In HS, GPx-rich loci, representing
      bundles of astrocytes, emerged in different hippocampal regions, whereas the
      number of GPx-positive vessels was drastically decreased. Neurons with abnormal
      morphology and strong MnSOD immunofluorescence were present in all neuronal
      layers in HS. Small autofluorescent deposits, most likely lipofuscin, were
      observed, along with astrogliosis, in CA1 in HS. SIGNIFICANCE: Antioxidative
      system is upregulated in HS. This documents, for the first time, that
      epileptogenic hippocampi are exposed to oxidative stress. Our findings provide a
      basis for understanding the potential involvement of redox alterations in the
      pathology of epilepsy, and may open new pharmacologic perspectives for mTLE-HS
      treatment.

PMID- 25864569
TI  - Population genetic insights into the social organization of Guinea baboons (Papio
      papio): Evidence for female-biased dispersal.
AB  - Sex differences in philopatry and dispersal have important consequences on the
      genetic structure of populations, social groups, and social relationships within
      groups. Among mammals, male dispersal and female philopatry are most common and
      closely related taxa typically exhibit similar dispersal patterns. However, among
      four well-studied species of baboons, only hamadryas baboons exhibit female
      dispersal, thus differing from their congenerics, which show female philopatry
      and close-knit female social relationships. Until recently, knowledge of the
      Guinea baboon social system and dispersal pattern remained sparse. Previous
      observations suggested that the high degree of tolerance observed among male
      Guinea baboons could be due to kinship. This led us to hypothesize that this
      species exhibits male philopatry and female dispersal, conforming to the
      hamadryas pattern. We genotyped 165 individuals from five localities in the
      Niokolo-Koba National Park, Senegal, at 14 autosomal microsatellite loci and
      sequenced a fragment of the mitochondrial hypervariable region I (HVRI) of 55
      individuals. We found evidence for higher population structuring in males than in
      females, as expected if males are the more philopatric sex. A comparison of
      relatedness between male-male and female-female dyads within and among
      communities did not yield conclusive results. HVRI diversity within communities
      was high and did not differ between the sexes, also suggesting female gene flow.
      Our study is the first comprehensive analysis of the genetic population structure
      in Guinea baboons and provides evidence for female-biased dispersal in this
      species. In conjunction with their multilevel social organization, this finding
      parallels the observations for human hunter-gatherers and strengthens baboons as
      an intriguing model to elucidate the processes that shaped the highly cooperative
      societies of Homo.

PMID- 25864571
TI  - Targeting aspirin in acute disabling ischemic stroke: an individual patient data
      meta-analysis of three large randomized trials.
AB  - BACKGROUND: Aspirin is of moderate overall benefit for patients with acute
      disabling ischemic stroke. It is unclear whether functional outcome could be
      improved after stroke by targeting aspirin to patients with a high risk of
      recurrent thrombosis or a low risk of haemorrhage. AIMS: We aimed to determine
      whether patients at higher risk of thrombotic events or poor functional outcome,
      or lower risk of major haemorrhage had a greater absolute risk reduction of poor
      functional outcome with aspirin than the average patient. METHODS: We used data
      on individual ischemic stroke patients from three large trials of aspirin vs.
      placebo in acute ischemic stroke: the first International Stroke Trial (n =
      18,372), the Chinese Acute Stroke Trial (n = 20,172) and the Multicentre Acute
      Stroke Trial (n = 622). We developed and evaluated clinical prediction models for
      the following: early thrombotic events (myocardial infarction, ischemic stroke,
      deep vein thrombosis and pulmonary embolism); early haemorrhagic events
      (significant intracranial haemorrhage, major extracranial haemorrhage, or
      haemorrhagic transformation of an infarct); and late poor functional outcome. We
      calculated the absolute risk reduction of poor functional outcome (death or
      dependence) at final follow-up in: quartiles of early thrombotic risk; quartiles
      of early haemorrhagic risk; and deciles of poor functional outcome risk. RESULTS:
      Ischemic stroke patients who were older, had lower blood pressure, computerized
      tomography evidence of infarct or more severe deficits due to stroke had
      increased risk of thrombotic and haemorrhagic events and poor functional outcome.
      Prediction models built with all baseline variables (including onset to treatment
      time) discriminated weakly between patients with and without recurrent thrombotic
      events (area under the receiver operating characteristic curve 0.56, 95% CI:0.53
      0.59) and haemorrhagic events (0.57, 0.52-0.64), though well between patients
      with and without poor functional outcome (0.77, 0.76-0.78) in the International
      Stroke Trial. We found no evidence that the net benefit of aspirin increased with
      increasing risk of thrombosis, haemorrhage or poor functional outcome in all
      three trials. CONCLUSIONS: Using simple clinical variables to target aspirin to
      patients after acute disabling stroke by risk of thrombosis, haemorrhage or poor
      functional outcome does not lead to greater net clinical benefit. We suggest
      future risk stratification schemes include new risk factors for thrombosis and
      intracranial haemorrhage.

PMID- 25864572
TI  - The effects of topical everolimus and sunitinib on corneal neovascularization.
AB  - PURPOSE: To evaluate the effects of topical everolimus and sunitinib on corneal
      neovascularization (CNV). METHODS: CNV was induced by application of silver
      nitrate to the cornea for all groups. Rats were divided into four groups of 10
      rats each, and two corneas were obtained from each rat. Group I received 1 mg/ml
      everolimus, Group II received 0.5 mg/ml sunitinib, Group IV received no treatment
      (control group) and Group IV received 1% Dimethylsulfoxide (DMSO). All treatments
      were administrated twice daily for 2 weeks. The right corneas were used for
      extracellular signal-regulated kinase 1/2 (ERK 1/2) protein analysis by western
      blot analysis and the left corneas were used for ERK 1/2 and vascular endothelial
      growth factor-receptor (VEGFR-2) gene expression analysis by quantitative real
      time PCR. RESULTS: VEGFR-2 mRNA expression levels (DeltaCt, median, min-max) were
      reduced in the everolimus 1.0 (0.25-1.81) and sunitinib 1.06 (0.24-2.68) treated
      groups compared with the control 4.74 (1.02-14.74) and DMSO groups 7.41 (0.72
      13.10). The expression of ERK 1/2 protein and mRNA levels were reduced in
      everolimus group compared with the control group (p < 0.05). These differences
      were not seen between the sunitinib and control groups. CONCLUSION: Topical
      administration of both everolimus and sunitinib reduced VEGFR-2 levels and
      inhibited CNV. In additon, everolimus reduced ERK 1/2 levels and seems to be more
      effective than sunitinib on CNV.

PMID- 25864573
TI  - Maternal health and pregnancy outcomes comparing migrant women born in
      humanitarian and nonhumanitarian source countries: a retrospective, observational
      study.
AB  - BACKGROUND: The relationship between migration and pregnancy outcomes is complex,
      with little insight into whether women of refugee background have greater risks
      of adverse pregnancy outcomes than other migrant women. This study aimed to
      describe maternal health, pregnancy care, and pregnancy outcomes among migrant
      women from humanitarian and nonhumanitarian source countries. METHODS:
      Retrospective, observational study of singleton births, at a single maternity
      service in Australia 2002-2011, to migrant women born in humanitarian source
      countries (HSCs, n = 2,713) and non-HSCs (n = 10,606). Multivariable regression
      analysis assessed associations between maternal HSC-birth and pregnancy outcomes.
      RESULTS: Compared with women from non-HSCs, the following were more common in
      women from HSCs: age < 20 years (0.6 vs 2.9% p < 0.001), multiparity (51 vs 76% p
      < 0.001), body mass index (BMI) >= 25 (38 vs 50% p < 0.001), anemia (3.2 vs 5.9%
      p < 0.001), tuberculosis (0.1 vs 0.4% p = 0.001), and syphilis (0.4 vs 2.5% p <
      0.001). Maternal HSC-birth was independently associated with poor or no pregnancy
      care attendance (OR 2.5 [95% CI 1.8-3.6]), late first pregnancy care visit (OR
      1.3 [95% CI 1.1-1.5]), and postterm birth (> 41 weeks gestation) (OR 2.5 [95% CI
      1.9-3.4]). Stillbirth (0.8 vs 1.2% p = 0.04, OR 1.5 [95% CI 1.0-2.4]) and
      unplanned birth before arrival at the hospital (0.6 vs 1.2% p < 0.001, OR 1.3
      [95% CI 0.8-2.1]) were more common in HSC-born women but not independently
      associated with maternal HSC-birth after adjusting for age, parity, BMI and
      relative socioeconomic disadvantage. CONCLUSIONS: These findings suggest areas
      where women from HSCs may have additional needs in pregnancy compared with women
      from non-HSCs. Refugee-focused strategies to support engagement in pregnancy care
      and address maternal health needs would be expected to improve health outcomes in
      resettlement countries.

PMID- 25864574
TI  - One-step generation of triple knockout CHO cell lines using CRISPR/Cas9 and
      fluorescent enrichment.
AB  - The CRISPR/Cas9 genome editing technology has previously been shown to be a
      highly efficient tool for generating gene disruptions in CHO cells. In this study
      we further demonstrate the applicability and efficiency of CRISPR/Cas9 genome
      editing by disrupting FUT8, BAK and BAX simultaneously in a multiplexing setup in
      CHO cells. To isolate Cas9-expressing cells from transfected cell pools, GFP was
      linked to the Cas9 nuclease via a 2A peptide. With this method, the average indel
      frequencies generated at the three genomic loci were increased from 11% before
      enrichment to 68% after enrichment. Despite the high number of genome editing
      events in the enriched cell pools, no significant off-target effects were
      observed from off-target prediction followed by deep sequencing. Single cell
      sorting of enriched multiplexed cells and deep sequencing of 97 clones revealed
      the presence of four single, 23 double and 34 triple gene-disrupted cell lines.
      Further characterization of selected potential triple knockout clones confirmed
      the removal of Bak and Bax protein and disrupted fucosylation activity as
      expected. The knockout cell lines showed improved resistance to apoptosis
      compared to wild-type CHO-S cells. Taken together, multiplexing with CRISPR/Cas9
      can accelerate genome engineering efforts in CHO cells even further. 

PMID- 25864575
TI  - Electrochemically Tunable Cell Adsorption on a Transparent and Adhesion
      Switchable Superhydrophobic Polythiophene Film.
AB  - A superhydrophobic polythiophene film (SSPTH) is prepared by double-layer
      electrodeposition on an indium tin oxide (ITO) glass electrode. This film shows
      not only electroresponsive superhydrophobic features, but also high transparency
      compared with the usual polythiophene film. The water-droplet adhesion on the
      SSPTH film can be switched between sliding and pinned states under the applied
      potential. More intresetingly, the change in water-droplet adhesion results in a
      change in cell adsorption on the SSPTH film. The low-adhesion (dedoped) SSPTH
      films can prevent Hela cell adhesion, whereas high-adhesion (doped) SSPTH films
      can promote Hela cell adsorption. This controllable cell adhesion on a SSPTH film
      may be developed as a smart biointerface material. 

PMID- 25864576
TI  - Biochemical and neuroimaging studies in subjective cognitive decline: progress
      and perspectives.
AB  - Neurodegeneration due to Alzheimer's disease (AD) can progress over decades
      before dementia becomes apparent. Indeed, patients with mild cognitive impairment
      (MCI) already demonstrate significant lesion loads. In most cases, MCI is
      preceded by subjective cognitive decline (SCD), which is applied to individuals
      who have self-reported memory-related complaints and has been associated with a
      higher risk of future cognitive decline and conversion to dementia. Based on the
      schema of a well-received model of biomarker dynamics in AD pathogenesis, it has
      been postulated that SCD symptoms may result from compensatory changes in
      response to beta-amyloid accumulation and neurodegeneration. Although SCD is
      considered a prodromal stage of MCI, it is also a common manifestation in old
      age, independent of AD, and the predictive value of SCD for AD pathology remains
      controversial. Here, we provide a review focused on the contributions of cross
      sectional and longitudinal analogical studies of biomarkers and neuroimaging
      evidence in disentangling under what conditions SCD may be attributable to AD
      pathology. In conclusion, there is promising evidence indicating that clinicians
      should be able to differentiate pre-AD SCD based on the presence of
      pathophysiological biomarkers in cerebrospinal fluid (CSF) and neuroimaging.
      However, this neuroimaging approach is still at an immature stage without an
      established rubric of standards. A substantial amount of work remains in terms of
      replicating recent findings and validating the clinical utility of identifying
      SCD. 

PMID- 25864577
TI  - Aqueous dye-sensitized solar cells.
AB  - Nowadays, dye-sensitized solar cells (DSSCs) are the most extensively
      investigated systems for the conversion of solar energy into electricity,
      particularly for implementation in devices where low cost and good performance
      are required. Nevertheless, a key aspect is still to be addressed, being
      considered strongly harmful for a long time, which is the presence of water in
      the cell, either in the electrolyte or at the electrode/electrolyte interface.
      Here comes the present review, in the course of which we try our best to address
      the highly topical role of water in DSSCs, trying to figure out if it is a
      poisoner or the keyword to success, by means of a thoroughly detailed analysis of
      all the established phenomena in an aqueous environment. Actually, in the last
      few years the scientific community has suddenly turned its efforts in the
      direction of using water as a solvent, as demonstrated by the amount of research
      articles being published in the literature. Indeed, by means of DSSCs fabricated
      with water-based electrolytes, reduced costs, non-flammability, reduced
      volatility and improved environmental compatibility could be easily achieved. As
      a result, an increasing number of novel electrodes, dyes and electrolyte
      components are continuously proposed, being highly challenging from the materials
      science viewpoint and with the golden thread of producing truly water-based
      DSSCs. If the initial purpose of DSSCs was the construction of an artificial
      photosynthetic system able to convert solar light into electricity, the use of
      water as the key component may represent a great step forward towards their
      widespread diffusion in the market. 

PMID- 25864579
TI  - The effect of the sphingosine-1-phosphate analogue FTY720 on atrioventricular
      nodal tissue.
AB  - The sphingosine-1-phosphate (S1P) receptor modulator, fingolimod (FTY720), has
      been used for the treatment of patients with relapsing forms of multiple
      sclerosis, but atrioventricular (AV) conduction block have been reported in some
      patients after the first dose. The underlying mechanism of this AV node
      conduction blockade is still not well-understood. In this study, we hypothesize
      that expression of this particular arrhythmia might be related to a direct effect
      of FTY720 on AV node rather than a parasympathetic mimetic action. We, therefore,
      investigated the effect of FTY720 on AV nodal, using in vitro rat model
      preparation, under both basal as well as ischaemia/reperfusion conditions. We
      first look at the expression pattern of S1P receptors on the AV node using real
      time PCR. Although all three S1P receptor isoforms were expressed in AVN tissues,
      S1P1 receptor isoform expression level was higher than S1P2 and S1P3. The effect
      of 25 nM FTY720 on cycle length (CL) was subsequently studied via extracellular
      potentials recordings. FTY720 caused a mild to moderate prolongation in CL by an
      average 9% in AVN (n = 10, P < 0.05) preparations. We also show that FTY720
      attenuated both ischaemia and reperfusion induced AVN rhythmic disturbance. To
      our knowledge, these remarkable findings have not been previously reported in the
      literature, and stress the importance for extensive monitoring period in certain
      cases, especially in patients taking concurrently AV node blocker agents. 

PMID- 25864580
TI  - Successful renal transplantation in a patient with a Wiskott-Aldrich syndrome
      protein (WASP) gene mutation.
AB  - Wiskott-Aldrich syndrome (WAS) is a rare primary immunodeficiency disorder caused
      by mutations in the WAS protein (WASP) gene. Renal disease progressing to renal
      failure is a well-recognized complication in patients with WAS. Only a few case
      reports of renal transplantation have been reported to date. Here, we present a
      patient with a WASP mutation who suffered from severe atopic eczema, mild
      thrombocytopenia and only a slightly increased frequency of infections, who then
      developed IgA nephropathy and consequently underwent renal transplantation, which
      was successful. This study demonstrates that renal transplantation is possible in
      patients with WAS, regardless of conceivable complications. 

PMID- 25864582
TI  - Abstracts of scientific papers 19th world congress on disaster and emergency
      medicine.

PMID- 25864581
TI  - The Relationships Between Functional Limitation, Depression, Suicidal Ideation,
      and Coping in Older Korean Immigrants.
AB  - Older adults with functional limitations may be at higher risk for depression and
      suicidal ideation compared to their counterparts without such limits. This study
      examined the structural relationships between functional limitation, depression,
      suicidal ideation, and coping strategies in older Korean immigrants. Using data
      from 220 community dwelling Korean immigrants (age ? 65) in Los Angeles County,
      path analysis was conducted to test the study hypotheses. The resulting model
      accounted for 56% of the variance in suicidal ideation, with functional
      limitation making significant contribution to suicidal ideation. Meanwhile,
      depression, which had the strongest direct effects on suicidal ideation, also
      played a significant role in mediating between functional limitation and suicidal
      ideation. Furthermore, adaptive coping was significantly associated with both
      functional limitation and suicidal ideation. Findings provide implications for
      implementing suicide-prevention programs for older Korean immigrants, especially
      those living with functional disability.

PMID- 25864578
TI  - Astrocyte VAMP3 vesicles undergo Ca2+ -independent cycling and modulate glutamate
      transporter trafficking.
AB  - KEY POINTS: Mouse cortical astrocytes express VAMP3 but not VAMP2. VAMP3 vesicles
      undergo Ca(2+) -independent exo- and endocytotic cycling at the plasma membrane.
      VAMP3 vesicle traffic regulates the recycling of plasma membrane glutamate
      transporters. cAMP modulates VAMP3 vesicle cycling and glutamate uptake.
      ABSTRACT: Previous studies suggest that small synaptic-like vesicles in
      astrocytes carry vesicle-associated vSNARE proteins, VAMP3 (cellubrevin) and
      VAMP2 (synaptobrevin 2), both contributing to the Ca(2+) -regulated exocytosis of
      gliotransmitters, thereby modulating brain information processing. Here, using
      cortical astrocytes taken from VAMP2 and VAMP3 knock-out mice, we find that
      astrocytes express only VAMP3. The morphology and function of VAMP3 vesicles were
      studied in cultured astrocytes at single vesicle level with stimulated emission
      depletion (STED) and total internal reflection fluorescence (TIRF) microscopies.
      We show that VAMP3 antibodies label small diameter (~80 nm) vesicles and that
      VAMP3 vesicles undergo Ca(2+) -independent exo-endocytosis. We also show that
      this pathway modulates the surface expression of plasma membrane glutamate
      transporters and the glutamate uptake by astrocytes. Finally, using
      pharmacological and optogenetic tools, we provide evidence suggesting that the
      cytosolic cAMP level influences astrocytic VAMP3 vesicle trafficking and
      glutamate transport. Our results suggest a new role for VAMP3 vesicles in
      astrocytes.

PMID- 25864583
TI  - A mitochondrion targeting fluorescent probe for imaging of intracellular
      superoxide radicals.
AB  - An amine-reactive fluorogenic molecule specifically turned on by superoxide
      radicals (O2(-)) was synthesized and coupled to a mitochondrial (MT) targeting
      peptide. The obtained probe showed superior uptake and MT targeting capabilities;
      and successfully detected the change in O2(-) levels in cells treated with
      chemical stimuli or single-walled carbon nanotubes. 

PMID- 25864584
TI  - A systematic review on the correlation between skeletal and jawbone mineral
      density in osteoporotic subjects.
AB  - OBJECTIVES: The aim of this systematic review was to assess whether the systemic
      skeletal reduction of bone mineral density (BMD) that characterizes osteoporotic
      subjects is also associated with a reduction of BMD in the jawbones. MATERIAL AND
      METHODS: Two reviewers searched independently and in duplicate three databases up
      to May 2014 and assessed the risk of bias using a tailored version of the
      Newcastle-Ottawa scale (NOS). Only papers reporting either Pearson's correlation
      coefficient or Spearman's rank correlation coefficient between skeletal and
      jawbone mineral density in more than five osteoporotic subjects were selected.
      RESULTS: From 1763 citations, 64 full-text papers were screened and five papers
      that met the inclusion criteria were included in the final analysis. None of the
      included studies complied with all NOS criteria, and as only two studies were
      eligible for meta-analysis, this was not performed. CONCLUSIONS: Only limited
      conclusions can be drawn from this systematic review, due to the small number of
      studies included, their heterogeneity, and their high risk of bias. Future
      studies that take into consideration both upper and lower jaws, that use the same
      technique to measure skeletal and jaw BMD (ideally dual-energy X-ray
      absorptiometry, DXA), and that account for confounding variables (such as
      medications/diseases affecting bone metabolism and demographics) are needed to
      provide more robust conclusions.

PMID- 25864585
TI  - CIDP-like neuropathies in graft versus host disease.
AB  - Cases of chronic inflammatory demyelinating poliradiculoneuropathy (CIDP) have
      been reported in hematopoietic stem cells transplantation complicated by graft
      versus host disease (GVHD). A systematic review of the CIDP-like neuropathies
      associated with GVHD was conducted until January 2015, analyzing the clinical
      presentation and the response to different therapeutic regimens. Nineteen
      patients have been reported in literature including the present one. Fourteen
      subjects fulfilled the criteria for CIDP, whereas two cases presented with an
      asymmetric motor onset and one showed motor involvement only associated with anti
      ganglioside antibodies. In addition, two subjects already affected by CIDP
      developed a significant relapse after GVHD. This study reviews the literature
      data and reports one additional case of CIDP and GVHD, suggesting that the two
      clinical entities might share a similar immunological background. 

PMID- 25864586
TI  - Expert Insight into the Assessment of Competence in Cognitive-Behavioural
      Therapy: A Qualitative Exploration of Experts' Experiences, Opinions and
      Recommendations.
AB  - To offer insight into how cognitive-behavioural therapy (CBT) competence is
      defined, measured and evaluated and to highlight ways in which the assessment of
      CBT competence could be further improved, the current study utilizes a
      qualitative methodology to examine CBT experts' (N = 19) experiences of
      conceptualizing and assessing the competence of CBT therapists. Semi-structured
      interviews were used to explore participants' experiences of assessing the
      competence of CBT therapists. Interview transcripts were then analysed using
      interpretative phenomenological analysis in order to identify commonalities and
      differences in the way CBT competence is evaluated. Four superordinate themes
      were identified: (i) what to assess, the complex and fuzzy concept of CBT
      competence; (ii) how to assess CBT competence, selecting from the toolbox of
      assessment methods; (iii) who is best placed to assess CBT competence, expertise
      and independence; and (iv) pitfalls, identifying and overcoming assessment
      biases. Priorities for future research and ways in which the assessment of CBT
      competence could be further improved are discussed in light of these findings.
      Copyright (c) 2015 John Wiley & Sons, Ltd. KEY PRACTITIONER MESSAGE: A
      qualitative exploration of experts' experiences, opinions and recommendations for
      assessing the competence of CBT therapists. Semi-structured interviews were
      conducted and analysed using interpretive phenomenological analysis. Themes
      identified shed light on (i) what to assess; (ii) how to assess; (iii) who is
      best placed to assess; and (iv) common pitfalls. Priorities for future research
      and ways in which the assessment of CBT competence could be further improved are
      discussed in light of these findings.

PMID- 25864588
TI  - Giant Negative Electrocaloric Effect in Antiferroelectric La-Doped Pb(ZrTi)O3
      Thin Films Near Room Temperature.
AB  - Antiferroelectric thin films are demonstrated as a new class of giant
      electrocaloric materials that exhibit a negative electrocaloric response of about
      -5 K near room temperature. The giant negative electrocaloric effect may open up
      a new paradigm for light, compact, reliable, and high-efficiency refrigeration
      devices. 

PMID- 25864587
TI  - Targeting MYCN IRES in MYCN-amplified neuroblastoma with miR-375 inhibits tumor
      growth and sensitizes tumor cells to radiation.
AB  - The MYCN oncogene is amplified in 20% of neuroblastomas, leading to its
      overexpression at both the mRNA and protein levels. MYCN overexpression is
      strongly associated with advanced disease stage, rapid tumor progression and a
      worse prognosis. In the present study, we identified microRNA-375 (miR-375) as a
      negative regulator of MYCN: enforced expression of miR-375 inhibited MYCN
      amplified neuroblastoma in vitro and in vivo. Upon searching the website miRbase
      for possible miR-375 binding sites within the whole MYCN mRNA, we found that the
      MYCN 5'-UTR had significant sequence complementarity to miR-375, yet no
      complementary sequences existed within the MYCN 3'-UTR and coding regions.
      Enforced overexpression of miR-375 efficiently inhibited MYCN mRNA translation
      and protein synthesis, via an IRES-dependent mechanism. In athymic nude mouse
      model with human MYCN-amplified neuroblastoma, MYCN downregulation by miR-375 led
      to inhibition of tumor cell growth and tumorigenicity. In particular, miR-375
      regulated inhibition of MYCN translation was enhanced when MYCN-amplified
      neuroblastoma cells were exposed to stress stimulation, such as ionizing
      irradiation (IR), resulting in a remarkable increase in the neuroblastoma's
      sensitivity to IR-induced cell death. Our results identified a novel mechanism by
      which IRES-dependent translation of MYCN is repressed by miR-375, particularly
      during cellular stress, highlighting a potential anticancer strategy: the
      development of miR-375 as a novel therapeutic agent to treat MYCN-amplified
      neuroblastoma. 

PMID- 25864589
TI  - Tobacco smoke induces production of chemokine CCL20 to promote lung cancer.
AB  - Tobacco kills nearly 6 million people each year, and 90% of the annual 1.59
      million lung cancer deaths worldwide are caused by cigarette smoke. Clinically, a
      long latency is required for individuals to develop lung cancer since they were
      first exposed to smoking. In this study, we aimed to identify clinical relevant
      inflammatory factors that are critical for carcinogenesis by treating normal
      human lung epithelial cells with tobacco carcinogen nicotine-derived
      nitrosaminoketone (NNK) for a long period (60 days) and systematic screening in
      84 cytokines/chemokines. We found that a chemokine CCL20 was significantly up
      regulated by NNK, and in 78/173 (45.1%) patients the expression of CCL20 was
      higher in tumor samples than their adjacent normal lung tissues. Interestingly,
      CCL20 was up-regulated in 48/92 (52.2%) smoker and 29/78 (37.2%) nonsmoker
      patients (p = 0.05), and high CCL20 was associated with poor prognosis. NNK
      induced the production of CCL20, which promoted lung cancer cell proliferation
      and migration. In addition, an anti-inflammation drug, dexamethasone, inhibited
      NNK-induced CCL20 production and suppressed lung cancer in vitro and in vivo.
      These results indicate that CCL20 is crucial for tobacco smoke-caused lung
      cancer, and anti-CCL20 could be a rational approach to fight against this deadly
      disease. 

PMID- 25864591
TI  - Silencing of MICAL-L2 suppresses malignancy of ovarian cancer by inducing
      mesenchymal-epithelial transition.
AB  - Ovarian cancer remains the disease with the highest associated mortality rate of
      gynecologic malignancy due to cancer metastasis. Rearrangement of actin
      cytoskeleton by cytoskeleton protein plays a critical role in tumor cell
      metastasis. MICAL-L2, a member of MICAL family, can interact with actin-binding
      proteins, regulate actin cross-linking and coordinate the assembly of adherens
      junctions and tight junctions. However, the roles of MICAL-L2 in tumors and
      diseases have not been explored. In this study, we found that MICAL-L2 protein is
      significantly up-regulated in ovarian cancer tissues along with FIGO stage and
      associated with histologic subgroups of ovarian cancer. Silencing of MICAL-L2
      suppressed ovarian cancer cell proliferation, migration and invasion ability.
      Moreover, silencing of MICAL-L2 prevented nuclear translocation of beta-catenin,
      inhibited canonical wnt/beta-catenin signaling and induced the mesenchymal
      epithelial transition (MET). Taken together, our data indicated that MICAL-L2 may
      be an important regulator of epithelial-mesenchymal transition (EMT) in ovarian
      cancer cells and a new therapeutic target for interventions against ovarian
      cancer invasion and metastasis. 

PMID- 25864592
TI  - Understanding intentions from actions: Direct perception, inference, and the
      roles of mirror and mentalizing systems.
AB  - This review asks whether observers can obtain information about others'
      intentions from observation of their actions; and if so, whether this process is
      performed using direct perceptual or inferential processes (prominent examples of
      each being the intention understanding theory of mirror neuron function, and
      mentalizing accounts of intention understanding, respectively). I propose four
      conditions that should be fulfilled in order to support a direct perception
      account, and suggest that only two of these conditions are supported by the
      existing data. I then propose and review three further sources of evidence which
      have the potential to inform this debate, concluding that the data do not support
      the direct perception account. In particular, mirror neurons may be involved in
      lower-level processes of action perception, but there is no evidence to support
      their involvement in the type of higher-level intention understanding that is
      proposed by the direct perception account. 

PMID- 25864590
TI  - Increased in vitro and in vivo sensitivity of BRCA2-associated pancreatic cancer
      to the poly(ADP-ribose) polymerase-1/2 inhibitor BMN 673.
AB  - BRCA2-associated pancreatic ductal adenocarcinoma (PDAC) may be sensitive to
      agents that target homology-directed DNA repair, such as DNA crosslinking agents
      (DCLs) and PARP inhibitors (PARPis). Here, we assessed the sensitivities of BRCA2
      deficient (Capan-1) and BRCA2-proficient (MIA PaCa-2) PDAC cell lines to a panel
      of DCLs and PARPis. Compared to MIA PaCa-2, Capan-1 was significantly more
      sensitive to all tested DCLs and PARPis, with similar increased sensitivities to
      cisplatin and the PARPi BMN 673 compared to other DCLs and the PARPi veliparib.
      We provide further support for this observation by showing that shRNA-mediated
      BRCA2 knockdown in PANC-1, a BRCA2-proficient cell line, induces sensitization to
      cisplatin and BMN 673 but not to veliparib. These findings were validated in a
      PDAC murine xenograft model derived from a patient with bi-allelic BRCA2
      mutations. We found 64% and 61% tumor growth inhibition of this xenograft with
      cisplatin and BMN 673 treatments, respectively. Cisplatin and BMN 673 treatments
      reduced cellular proliferation and induced apoptosis. Our findings support a
      personalized treatment approach for BRCA2-associated PDAC. 

PMID- 25864593
TI  - A Bayesian approach to person perception.
AB  - Here we propose a Bayesian approach to person perception, outlining the
      theoretical position and a methodological framework for testing the predictions
      experimentally. We use the term person perception to refer not only to the
      perception of others' personal attributes such as age and sex but also to the
      perception of social signals such as direction of gaze and emotional expression.
      The Bayesian approach provides a formal description of the way in which our
      perception combines current sensory evidence with prior expectations about the
      structure of the environment. Such expectations can lead to unconscious biases in
      our perception that are particularly evident when sensory evidence is uncertain.
      We illustrate the ideas with reference to our recent studies on gaze perception
      which show that people have a bias to perceive the gaze of others as directed
      towards themselves. We also describe a potential application to the study of the
      perception of a person's sex, in which a bias towards perceiving males is
      typically observed. 

PMID- 25864594
TI  - Decompression surgery for severe traumatic brain injury (TBI): A long-term,
      single-centre experience.
AB  - INTRODUCTION: Despite well-conducted medical treatment, refractory intracranial
      hypertension occurs in 10-15% of patients with severe traumatic brain injury
      (TBI). Surgical decompression procedures, such as hemicraniectomy, are mainly
      considered as a rescue therapy. However, the long-term neurological outcomes of
      these patients remain controversial. Thus, the purpose of this study was to
      investigate the long-term evolution of patients requiring surgical decompression
      surgery in our ICU over the last 7 years. METHODS: We conducted a retrospective
      single-centre study over the last 7 years. Severe traumatic brain injury patients
      presenting a refractory intracranial hypertension (ICP) and who underwent
      decompression surgery were included. Demographic data, in-hospital complications
      (infectious diseases, seizures) and in-hospital mortality were studied. Patients
      were further (from 1 to 8 years post injury) contacted for questioning including
      evaluation of the Glasgow Outcome Scale (GOS), recovery of professional activity,
      concentration disorders, motor and mood disabilities, sleep disorders, headaches,
      or seizure occurrences. We compared this population with patients presenting
      elevated ICP not needing surgery, and matched on gender, age, SAPS II scores,
      initial GCS, and time since TBI. RESULTS: Twenty patients required decompression
      surgery during the studied period (2%), half of whom deceased during that time.
      Among surviving patients, 22% had seizures. Memory disorders represented the most
      frequently reported disability (100% of questioned patients). Half of the
      patients presented sleep disorders and headaches after hospitalization. Only 33%
      of these patients recovered a professional activity after treatment. Compared to
      the matched population, long-term neurological status was equivalent in
      survivors. CONCLUSION: In this small retrospective study, we found that
      decompression surgery performed for traumatic refractory raised ICP concerned
      only 2% of our traumatic brain injury patients. According to long-term
      evaluation, decompression surgery is associated with unfavourable outcomes and
      disabilities. However, the functional recovery and quality of life in survivors
      seems equivalent to a matched population. These results require confirmation via
      larger studies.

PMID- 25864599
TI  - New developments on the neurobiological and pharmaco-genetic mechanisms
      underlying internet and videogame addiction.
AB  - BACKGROUND: There is emerging evidence that the psychobiological mechanisms
      underlying behavioral addictions such as internet and videogame addiction
      resemble those of addiction for substances of abuse. OBJECTIVES: Review of brain
      imaging, treatment and genetic studies on videogame and internet addiction.
      METHODS: Literature search of published articles between 2009 and 2013 in Pubmed
      using "internet addiction" and "videogame addiction" as the search word. Twenty
      nine studies have been selected and evaluated under the criteria of brain
      imaging, treatment, and genetics. RESULTS: Brain imaging studies of the resting
      state have shown that long-term internet game playing affected brain regions
      responsible for reward, impulse control and sensory-motor coordination. Brain
      activation studies have shown that videogame playing involved changes in reward
      and loss of control and that gaming pictures have activated regions similarly to
      those activated by cue-exposure to drugs. Structural studies have shown
      alterations in the volume of the ventral striatum possible as result of changes
      in reward. Furthermore, videogame playing was associated with dopamine release
      similar in magnitude to those of drugs of abuse and that there were faulty
      inhibitory control and reward mechanisms videogame addicted individuals. Finally,
      treatment studies using fMRI have shown reduction in craving for videogames and
      reduced associated brain activity. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE:
      Videogame playing may be supported by similar neural mechanisms underlying drug
      abuse. Similar to drug and alcohol abuse, internet addiction results in sub
      sensitivity of dopamine reward mechanisms. Given the fact that this research is
      in its early stage it is premature to conclude that internet addiction is
      equivalent to substance addictions.

PMID- 25864598
TI  - Typologies of positive psychotic symptoms in methamphetamine dependence.
AB  - BACKGROUND AND OBJECTIVES: Understanding methamphetamine associated psychotic
      (MAP) symptom typologies could aid in identifying individuals at risk of
      progressing to schizophrenia and guide early intervention. METHODS: Latent class
      analysis (LCA) of psychotic symptoms collected from 40 (n = 40) methamphetamine
      dependent individuals with a history of psychotic symptoms but no history of a
      primary psychotic disorder. RESULTS: Three typologies were identified. In one,
      persecutory delusions dominated (Type 1), in another persecutory delusions were
      accompanied by hallucinations (Type 2), and in the third a high frequency of all
      the assessed hallucinatory and delusional symptoms was observed (Type 3).
      DISCUSSION AND CONCLUSION: MAP is a heterogeneous syndrome with positive symptom
      typologies. SCIENTIFIC SIGNIFICANCE: This study represents the first attempt at
      identifying typologies of MAP and highlights the potential utility of LCA in
      future large-scale studies.

PMID- 25864600
TI  - Gambling disorder and its relationship with substance use disorders: implications
      for nosological revisions and treatment.
AB  - BACKGROUND: Gambling disorder, recognized by the DSM-5 as a behavioral addiction,
      affects .4-1.6% of adults worldwide, and is highly comorbid with other mental
      health disorders, particularly substance use disorders (SUDs). OBJECTIVES: To
      provide a concise primer on the relationship between gambling disorder and SUDs,
      focusing on phenomenology/clinical presentation, co-morbidity, familiality,
      cognition, neuroanatomy/neurochemistry, and treatment. METHODS: Selective review
      of the literature. RESULTS: Scientific evidence shows that gambling and SUDs have
      consistently high rates of comorbidity, similar clinical presentations, and some
      genetic and physiological overlap. Several treatment approaches show promise for
      gambling disorder, some of which have previously been effective for SUDs.
      SCIENTIFIC SIGNIFICANCE: It is hoped that recognition of overlap between gambling
      disorder and SUDs in terms of phenomenology and neurobiology will signal novel
      treatment approaches and raise the profile of this neglected condition.

PMID- 25864601
TI  - Compulsive buying.
AB  - OBJECTIVE: Although compulsive buying (CB) seems to be not only prevalent but
      even increasing in prevalence, it often remains neglected or minimized in
      clinical settings. There is a need for a greater understanding and recognition of
      this problem. The aim of this article is to summarize the current knowledge
      regarding CB and to offer thoughts regarding classification. METHOD: Review of
      published literature over the period 1994-2013 through Pubmed/Medline, PsychINFO,
      and Google Scholar using the key words 'compulsive buying', 'impulsive buying'
      and 'addictive buying'. RESULTS: CB is defined by a preoccupation with buying and
      shopping, by frequent buying episodes, or overpowering urges to buy that are
      experienced as irresistible and senseless. The maladaptive spending behavior is
      associated with serious psychological, social, occupational, and financial
      problems. Treatment-seeking patients with CB suffer from substantial psychiatric
      comorbidity (eg, anxiety and depressive mood disorders, compulsive hoarding,
      binge eating disorder). Representative surveys revealed prevalence estimates of
      CB between 6% and 7% and indicate that younger people are more prone to develop
      CB. Moreover, European data suggest an increase of CB in the adult population
      over the last 20 years. While there is no evidence for the efficacy of
      psychopharmacological treatment, group cognitive behavioral therapy has been
      shown to be effective. CONCLUSION: The relevance of recognition of CB as mental
      disorder is undeniable in the face of its estimated prevalence and associated
      burden. As our understanding of contributing neurobiological and etiological
      factors is limited, further research should focus on these topics, taking into
      account the heterogeneity of individuals with CB. There is also a need for
      specific treatment options and for the development of prevention strategies.

PMID- 25864602
TI  - Associations between chronic non-cancer pain and medication assisted treatment
      outcomes for opiate addiction.
AB  - BACKGROUND AND OBJECTIVES: An increased percentage of individuals entering opioid
      addiction treatment programs also report the presence of chronic non-cancer pain
      (CNCP). This study examined associations between the presence of CNCP and 6-month
      medication assisted addiction treatment (MAT) outcomes. METHODS: The sample
      included 585 individuals at opiate treatment programs who completed a structured
      intake interview and a 6-month follow-up telephone interview between March 2007
      and December 2010. Of the sample, 115 individuals reported CNCP at intake and 6
      month follow-up. Bivariate analyses compared individuals with CNCP (n = 115) and
      without CNCP (n = 470) at MAT intake. RESULTS: A greater percentage of
      individuals with CNCP were older, were retired or disabled, and had experienced
      depression or anxiety before intake compared to individuals without CNCP. Results
      of binomial logistic regression models found that having CNCP was associated with
      increased odds of depression/anxiety at follow-up, but had no association with
      employment or substance use. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: The
      correlations between CNCP and co-occurring depression/anxiety among MAT clients
      indicate an area of special concern for providers. A full biopsychosocial,
      including a focus on history of chronic physical pain, might be beneficial to
      help highlight potential co-morbidities and to encourage closer monitoring of the
      intertwining relationships between addiction, CNCP, and depression/anxiety.

PMID- 25864603
TI  - Intervention with substance-abusing mothers: are there rural-urban differences?
AB  - OBJECTIVE: The purpose of this study was to examine rural-urban differences among
      substance-abusing mothers enrolled in the Parent-Child Assistance Program (PCAP)
      from 1998 to 2008 in Washington State. METHODS: This was a longitudinal study
      utilizing PCAP data reports of 773 women enrolled from 1998 to 2008. Differences
      across urban-rural PCAP participants were examined. RESULTS: Rural participants
      were more likely to report alcohol use and binge drinking at program intake and
      at the 3-year program exit. In addition, throughout the program, rural women were
      less likely to complete outpatient substance abuse treatment compared to urban
      participants. Rural women also used less services during the last year including
      alcohol/drug support and mental health provider services. Findings are troubling
      when we consider that at program exit, rural participants also reported higher
      use of alcohol and more suicidal thoughts than those residing in urban areas.
      CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Data presented indicate there are
      important differences between urban and rural residing participants. Findings
      highlight the importance of considering the barriers that rural or remote
      locations might create. Identifying community-specific needs of substance abusing
      pregnant or parenting women in both rural and urban settings is crucial for the
      successful development and improvement of treatment and intervention programs for
      this vulnerable population of women.

PMID- 25864604
TI  - Self-reported physical activity in smoking pre-cessation is not a protective
      factor against relapse for all.
AB  - BACKGROUND: In recent years, the relationship between physical activity (PA) and
      smoking cessation has been increasingly studied. However, very few studies have
      investigated the possible protective role of PA on smoking relapse on the long
      term. OBJECTIVES: This study evaluated the impact of self-reported PA in
      precessation on smoking relapse. Other variables evaluated included measures of
      dependence, socio-demographic factors and smoking-related variables. Several
      possible interactions between PA and well identified factors influencing smoking
      relapse rate were also explored. METHODS: After the initial consultation, 345
      smokers were consecutively recruited in a smoking-cessation unit. Smoking
      abstinence was collected regularly during consultation or by phone calls. PA was
      measured with the International Physical Activity Questionnaire short form. Cox
      proportional hazard model was performed to determine factors associated with
      smoking relapse. RESULTS: Among the initial sample, 227 adults were included in
      the survival analysis. After adjustment for potential cofounders, PA was not
      associated with smoking relapse. Self-efficacy level, absence of professional
      activity, previous attempts to quit and alcohol use disorders were associated
      with relapse. Secondary analysis showed a statistically significant effect of an
      interaction term for PA and antidepressant use on reducing smoking relapse (HR =
      .81, 95% CI: .66-.99). CONCLUSION AND SCIENTIFIC SIGNIFICANCE: Previous quit
      attempts and professional activity were positive predictors of smoking
      abstinence, with alcohol use disorder a negative predictor. PA was not found to
      be a significant predictor of smoking relapse, with only a positive interaction
      term seen for persons on antidepressant treatment.

PMID- 25864605
TI  - Impact of marijuana use on self-rated cognition in young adult men and women.
AB  - BACKGROUND AND OBJECTIVES: Marijuana (MJ) is a widely used substance that has
      been shown to impair cognition in laboratory settings. There is a growing number
      of medical MJ dispensaries and state policies permitting the use of MJ in the
      United States. This study is a naturalistic study that explores the association
      of same day MJ use on self-rated cognition in young adult men and women. METHODS:
      Forty-eight (n = 48) young adults (22 F; mean age = 22.3) participated. After a
      baseline assessment, participants made daily phone calls to study staff over the
      next 3 weeks. Cumulative minutes of MJ use in the last 24-hours were assessed.
      Demographic information collected and self-ratings of cognitive impairment were
      assessed using six questions about areas of difficulty thinking each day.
      RESULTS: There was a significant relationship between greater number of minutes
      of MJ use and higher levels of self-rated cognitive difficulties (b = .004; SE =
      .001; p < .006). There was no main effect of gender (b = 1.0; SE = .81; p < .22).
      Planned evaluation of the interaction between gender and minutes of MJ use was
      not significant statistically, suggesting a similar relationship between minutes
      of MJ use and cognitive difficulties among women compared to men (p < .54).
      CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: There is an association between current
      and heavy MJ use and self-perceived cognitive ability in both males and females.
      These findings reveal important information regarding one consequence of MJ use
      that has real-world meaning to young adult smokers. (Am J Addict 2015;24:160
      165).

PMID- 25864606
TI  - Smoking-related correlates of psychomotor restlessness and agitation in a
      community sample of daily cigarette smokers.
AB  - BACKGROUND AND OBJECTIVES: Psychomotor restlessness and agitation (PMA) is a
      putatively important, yet understudied, psychopathologic correlate of smoking.
      The scant smoking research on PMA previously conducted has been narrow in scope
      and conducted among psychiatric patients. To examine the generalizability and
      relevance of PMA to smoking, this cross-sectional study investigated associations
      between PMA and a variety of smoking processes in a community sample. METHODS:
      Participants in this study were non-treatment-seeking smokers (N = 254, >=10
      cig/day, M age = 44 years) from the community without an active mood disorder. At
      baseline, they completed a PMA symptom checklist, a composite depressive symptom
      index, and a battery of smoking questionnaires. RESULTS: Linear regression models
      adjusting for depressive symptoms and demographics indicated that PMA level was
      positively associated with severity of nicotine withdrawal symptoms during prior
      quit attempts (beta = .18, p < .05), anticipated likelihood of withdrawal in a
      future quit attempt (beta = .19, p < .05), motivation to smoke for negative
      reinforcement (beta = .14, p < .05), and smoking expectancies for negative
      reinforcement (beta = .17, p < .05), negative consequences (beta = .22, p < .01),
      and positive reinforcement (beta = .14, p < .05). PMA was not significantly
      associated with smoking chronicity, frequency, or dependence severity. CONCLUSION
      AND SCIENTIFIC SIGNIFICANCE: Smokers with elevated PMA appear to experience
      greater smoking-induced affect modulation and nicotine withdrawal than the
      average smoker, regardless of other depressive symptoms. Given that PMA
      differentiates a qualitatively unique profile of smoking characteristics, PMA
      warrants consideration in tobacco addiction research and practice.

PMID- 25864607
TI  - Prescription medication misuse among opioid dependent patients seeking inpatient
      detoxification.
AB  - BACKGROUND AND OBJECTIVES: Opioid related morbidity and mortality is heightened
      in context to the concomitant use of psychotropic medications. The aim of this
      project was to examine the extent to which opioid dependent patients seeking
      detoxification are using and misusing specific psychotropic agents. METHODS: As
      part of a quality assurance/improvement project, we systematically assessed
      prospectively consecutive admissions to a public detoxification program using a
      self-report questionnaire to query for specific psychotropic medication use.
      Patients were asked about having a current prescription, appropriate use, and/or
      medical misuse (higher doses, using without prescription) of amphetamine salts,
      clonazepam, clonidine, gabapentin, and pregabalin. RESULTS: We had data on 196
      admissions including 162 patients with opioid dependency. Patients receiving
      detoxification from opioids compared to alcohol had statistically significant
      higher rates of medication misuse (30% vs. 0%, respectively; chi(2)  = 12.8, p <
      .0003). Of opioid dependent patients receiving prescription medication, 28%
      reported using higher amounts of each medication than prescribed. Of opioid
      patients, 10% self-reported misusing clonidine, 22% gabapentin, 7% pregabalin,
      25% clonazepam, 11% amphetamine salts, and 36% any of these medications.
      DISCUSSION AND CONCLUSIONS: Despite the "nonaddictive nature" of some medications
      (eg, gabapentin, clonidine), high rates of medication misuse in opioid dependent
      patients admitted for detoxification was found and appeared similar to rates of
      misuse among controlled substances such as clonazepam and amphetamine salts.
      These data suggest that opioid dependent patients should be queried for the
      appropriate use of prescribed medications and that practitioners need to monitor
      for medication misuse in opioid dependent patients.

PMID- 25864611
TI  - Midlife plasma vitamin D concentrations and performance in different cognitive
      domains assessed 13 years later.
AB  - 25-Hydroxyvitamin D (25(OH)D) insufficiency is very common in many countries.
      Yet, the extent to which 25(OH)D status affects cognitive performance remains
      unclear. The objective of the present study was to evaluate the cross-time
      association between midlife plasma 25(OH)D concentrations and subsequent
      cognitive performance, using a subsample from the French 'SUpplementation en
      Vitamines et Mineraux AntioXydants' randomised trial (SU.VI.MAX, 1994-2002) and
      the SU.VI.MAX 2 observational follow-up study (2007-9). 25(OH)D concentrations
      were measured in plasma samples drawn in 1994-5, using an electrochemoluminescent
      immunoassay. Cognitive performance was evaluated in 2007-9 with a
      neuropsychological battery including phonemic and semantic fluency tasks, the RI
      48 (rappel indice-48 items) cued recall test, the Trail Making Test and the
      forward and backward digit span. Cognitive factors were extracted via principal
      component analysis (PCA). Data from 1009 individuals, aged 45-60 years at
      baseline, with available 25(OH)D and cognitive measurements were analysed by
      multivariable linear regression models and ANCOVA, stratified by educational
      level. PCA yielded two factors, designated as 'verbal memory' (strongly
      correlated with the RI-48 and phonemic/semantic fluency tasks) and 'short
      term/working memory' (strongly correlated with the digit span tasks). In the
      fully adjusted regression model, among individuals with low education, there was
      a positive association between 25(OH)D concentrations and the 'short-term/working
      memory' factor (P=0.02), mainly driven by the backward digit span (P=0.004). No
      association with either cognitive factor was found among better educated
      participants. In conclusion, higher midlife 25(OH)D concentrations were linked to
      better outcomes concerning short-term and working memory. However, these results
      were specific to subjects with low education, suggesting a modifying effect of
      cognitive reserve.

PMID- 25864612
TI  - The role of nicotinic acetylcholine and opioid systems of the ventral orbital
      cortex in modulation of formalin-induced orofacial pain in rats.
AB  - Nicotinic acetylcholine and opioid receptors are involved in modulation of pain.
      In the present study, we investigated the effects of microinjection of nicotinic
      acetylcholine and opioid compounds into the ventral orbital cortex (VOC) on the
      formalin-induced orofacial pain in rats. For this purpose, two guide cannulas
      were placed into the left and right sides of the VOC of the brain. Orofacial pain
      was induced by subcutaneous injection of a diluted formalin solution (50MUl,
      1.5%) into the right vibrissa pad and face rubbing durations were recorded at 3
      min blocks for 45min. Formalin produced a marked biphasic pain response (first
      phase: 0-3min and second phase: 15-33min). Epibatidine (a nicotinic receptor
      agonist) at doses of 0.05, 0.1 and 0.2MUg/site, morphine (an opioid receptor
      agonist) at doses of 0.5, 1 and 2MUg/site and their sub-analgesic doses
      (0.025MUg/site epibatidine with 0.25MUg/site morphine) combination treatment
      suppressed the second phase of pain. The antinociceptive effect induced by
      0.2MUg/site of epibatidine, but not morphine (2MUg/site), was prevented by
      2MUg/site of mecamylamine (a nicotinic receptor antagonist). Naloxone (an opioid
      receptor antagonist) at a dose of 2MUg/site prevented the antinociceptive effects
      induced by 2MUg/site of morphine and 0.2MUg/site of epibatidine. No above
      mentioned chemical compounds affected locomotor activity. These results showed
      that at the VOC level, epibatidine and morphine produced antinociception. In
      addition, opioid receptor might be involved in epibatidine-induced
      antinociception, but the antinociception induced by morphine was not mediated
      through nicotinic acetylcholine receptor. 

PMID- 25864613
TI  - Evaluation of the antitumour activity of Rinvanil and Phenylacetylrinvanil on the
      cervical cancer tumour cell lines HeLa, CaSKi and ViBo.
AB  - Capsaicin is a potent inducer of apoptosis in tumourreceptor potential vanilloid
      1 (TRPV1). The present study determined the IC50 and cytotoxic and apoptotic
      activities of the Capsaicin analogues Rinvanil and Phenylacetylrinvanil (PhAR) on
      three cervical cancer cell lines: HeLa, CaSKi and ViBo. These analogues possess
      an increased affinity for TRPV1 receptors. The IC50 obtained proved to be
      cytotoxic for all three cell lines; however, in the cells treated with Capsaicin
      both active caspase-3 and nuclear fragmentation were present. Capsaicin and its
      analogues also inhibited the normal proliferation of lymphocytes, suggesting that
      they are non-selective antitumour compounds. Finally, we discuss the possible
      loss of the relation between apoptosis and affinity to TRPV1, and the need for
      other strategies to synthesise Capsaicin analogues that can be useful in cancer
      treatments. 

PMID- 25864614
TI  - Sonographic assessment of the effect of vesicoureteral reflux and urinary tract
      infections on growth of the pediatric solitary kidney.
AB  - INTRODUCTION: Perusal of recent guidelines relating to proper evaluation of
      infants and children with urinary tract infection (UTI) suggests that the
      occurrence of vesicoureteral reflux (VUR) may not have the clinical import
      previously ascribed to this anatomic abnormality. Patients with a solitary kidney
      uniquely allow investigation of the effects of both vesicoureteral reflux (VUR)
      and urinary tract infection (UTI) on renal growth unencumbered with the
      inevitable questions of laterality that confound analysis in patients with two
      kidneys. Several previous studies with conflicting results have addressed whether
      vesicoureteral reflux (VUR) impacts ultimate renal size in children with a
      solitary kidney. Few published studies have considered the occurrence of both
      urinary tract infection (UTI) and VUR on the degree of compensatory hypertrophy.
      This is the largest series to date investigating the effect of both UTI and VUR
      on the degree of compensatory hypertrophy with time. OBJECTIVE: Our objective was
      to analyze sonographically determined renal growth in patients with a solitary
      kidney, stratifying for both the occurrence and severity of UTIs and the
      occurrence and severity of VUR. STUDY DESIGN: We retrospectively reviewed the
      clinical history (including bladder and bowel dysfunction (BBD)) and radiology
      reports of 145 patients identified as having either a congenital or acquired
      solitary kidney in our pediatric urology practice from the prior 10 years. UTIs
      were tabulated by severity, where possible, and the grade of VUR was recorded
      based on the initial cystogram. Sonographically determined renal length was
      tabulated for all ultrasounds obtained throughout the study. Based on a mixed
      effects model, we investigated the influence of UTI and VUR on renal growth.
      RESULTS: Of the 145 patients analyzed, 105 had no VUR and 39 had VUR (16 = Gr
      I&II, 11 = GIII, 12 = GIV&V). Comparison showed that there was no difference in
      the occurrence of UTI between those without VUR (27/105 with UTI) and those with
      VUR (15/39 with UTI; p = 0.14). There was no difference in the occurrence of BBD
      in patients with VUR (15/39) and those without VUR (36/106, p = 0.62). While
      neither VUR nor UTI alone affected renal growth in the solitary kidney, the three
      way interaction term among age, VUR, and UTI was significant (p = 0.016). The
      growth of the kidneys in the various patient groups is depicted in the table.
      From the analysis, a refluxing solitary kidney with UTI showed a significantly
      lower growth rate than the other groups (p < 0.001). DISCUSSION: This study is
      limited by the inherent selection bias of retrospective studies. Additionally,
      the variability of sonographic renal measurement is well recognized. Lastly, our
      sample size did not allow us to incorporate the severity of the UTIs and the
      grades of VUR in our final regression model. Nevertheless, the overall patterns
      suggest that when both VUR and UTI are present, the solitary kidney demonstrates
      less renal growth with time. Study of larger cohorts of patients with solitary
      kidneys will be necessary to confirm our observations and discern what, if any,
      are the consequences of high-grade VUR and upper tract UTI in these patients.
      CONCLUSION: In the largest series to date we were able to discern no independent
      effect of either VUR or UTI on sonographically determined renal growth in
      patients with a solitary kidney. However, UTI and VUR together result in kidneys
      that are smaller than other solitary kidneys not so affected. Follow-up studies
      of larger cohorts seem warranted to confirm these findings and discern the
      clinical import of these smaller kidneys.

PMID- 25864615
TI  - Objective pain assessment after ureteral reimplantation: comparison of open
      versus robotic approach.
AB  - INTRODUCTION: While open ureteral reimplantation is the gold standard of surgical
      intervention for vesicoureteral reflux (VUR), minimally invasive approaches offer
      the potential benefits of decreased postoperative pain, improved cosmesis, and
      shorter hospital stay and convalescence. Studies comparing open and minimally
      invasive surgery with respect to postoperative pain in children have been
      inconclusive. OBJECTIVE: We sought to compare postoperative pain in children
      undergoing open versus robotic ureteral reimplantation by using age-appropriate,
      validated pain assessment scales. METHODS: A prospective cohort of all patients
      enrolled in an Institutional Review Board-approved VUR surgery registry between
      July 2010 and February 2013 was analyzed. Patients who underwent endoscopic
      treatment or who received caudal or epidural anesthesia were excluded. Age
      appropriate, validated pain scales ranging from 0 to 10 were utilized for pain
      assessment. Pain scores and narcotic doses administered on the first
      postoperative day were analyzed. RESULTS: Of the 34 subjects included, 11
      underwent open intravesical reimplantation, while 23 patients underwent robotic
      extravesical reimplantation. Table 1 displays patient characteristics and results
      of pain assessment. Robotic surgery was associated with lower narcotic
      requirement compared to open surgery (P < 0.05). The difference in pain scores
      between the two cohorts approached, but did not reach, statistical significance
      (P = 0.12). However, the percentage of patients with mild or no pain (57%
      robotic, 27% open) versus severe pain (9% robotic, 45% open) was notably
      different between the two cohorts. DISCUSSION: Previous studies addressing the
      effect of surgical modality on pediatric postoperative pain are limited by their
      reliance on narcotic administration as an indirect surrogate for measuring pain.
      In the present study, postoperative pain was assessed with narcotic requirements
      and consistently collected validated pain scores, which more accurately reflect a
      patient's perceived pain. Although there was no significant difference in
      subjective pain scores between patients undergoing open versus robotic
      reimplantation, the percentage of patients with mild or no pain (57% robotic, 27%
      open) versus severe pain (9% robotic, 45% open) was notably different between the
      two cohorts. This study was limited by a lack of randomization as well as small
      sample size, which did not allow for age sub-group analysis or small differences
      to be statistically significant. CONCLUSIONS: In the present study, robotic
      ureteral reimplantation was associated with lower narcotic requirement compared
      to open surgery, and lower intensity of postoperative pain according to a direct
      pain assessment tool. Larger sample sizes are necessary to strengthen statistical
      comparisons.

PMID- 25864616
TI  - The effect of spinal cord level on sexual function in the spina bifida
      population.
AB  - INTRODUCTION: Sexual dysfunction and infertility are prevalent in the spina
      bifida (SB) population; however, the mechanism of how they affect a person with
      spina bifida is poorly understood. Additionally, the management of children with
      spina bifida becomes more difficult as they exit from pediatric institutes.
      OBJECTIVE: The present study sought to evaluate sexual health (using validated
      questionnaires) and fertility in adults with spina bifida and to correlate spinal
      cord level and ambulatory status with degree of sexual function. STUDY DESIGN:
      After institutional board review approval, 199 adult patients with SB, aged 18
      and older and who were followed in one pediatric institution, were identified.
      Patients who were non-English speaking, cognitively and/or developmentally
      delayed, or unable to be contacted were excluded. Surveys regarding demographics,
      sexual health and infertility were mailed to the patients and administered in the
      clinic with the option to opt-out of the survey. Survey questions regarding
      sexual health were constructed using validated questionnaires: Female Sexual
      Function Index (FSFI) for females, and International Index of Erectile Function
      (IIEF) and Sexual Health Inventory for Men (SHIM) for males. Sexual dysfunction
      scores were correlated to the patients' spinal level and ambulatory status.
      RESULTS: Of the 121 eligible patients, 45 replied, with a response rate of 39%.
      For females, using a cut-off value of 26.5 for FSFI scoring, 25 out of 28 (89%)
      had sexual dysfunction. No association was seen between spinal level or
      ambulatory status and overall FSFI, satisfaction, or desire scores. For males, 10
      out of 17 (59%) had severe erectile dysfunction (ED), and one out of 17 (6%) had
      no ED. No association was seen between ambulatory status and sexual function
      scores for the males. However, SHIM, satisfaction, and ED scores were higher in
      males with lower spinal lesions. People with spina bifida of both genders tended
      to have more severe dysfunction compared to those with sexual dysfunction of
      other etiologies, except with similar sexual desire scores. Regarding questions
      on fertility, no participant attempted to have children; thus, there was no
      infertility reported. DISCUSSION: Few studies have been conducted on sexual
      health and fertility in adults with SB. Three studies have utilized validated
      questionnaires and found varying degrees of sexual dysfunction in this subset of
      patients; however, only one study found sexual activity to be more likely in
      patients with more caudal levels of neurologic impairment. The present study also
      showed that SHIM, satisfaction, and ED scores were higher in males with lower
      spinal lesions. Limitations to this study primarily included the small sample
      size and low survey response rate. CONCLUSION: Limited information is known about
      adults with SB, and sexual function and fertility. While expressing sexual
      desire, adults with SB appear to experience high rates of sexual dysfunction.
      Fertility rates were inadequately assessed; this was possibly due to the high
      rate of sexual dysfunction. Sexual health in the SB population is an important
      component of the myriad of urologic care issues for these people. Due to the
      disparity in their care after reaching adulthood, it is prudent to follow these
      patients and understand their pathophysiology as they continue to mature through
      life.

PMID- 25864617
TI  - MicroRNA-106b regulates pro-allergic properties of dendritic cells and Th2
      polarisation by targeting early growth response-2 in vitro.
AB  - Recent evidence has suggested that miRNA is implicated in the immune response of
      allergic and inflammatory diseases. However, little is known about its role in
      the mechanism that underlies the establishment of pro-allergic DCs in allergic
      rhinitis is not fully understood. This study assessed whether and how microRNA
      (miR)-106b regulates the pro-allergic properties of DCs upon allergen stimulation
      in vitro. Bone marrow-derived dendritic cells (BMDCs) were generated and
      stimulated with ovalbumin (OVA) to identify the miRNA expression profile. After
      transfection with miR-106b mimics and inhibitors OVA-activated BMDCs were further
      evaluated for surface marker expression using flow cytometry, cytokine production
      using ELISA and subsequent effects on Th2 cell polarisation using flow cytometry.
      Moreover, the upstream controllers and potential target proteins of miR-106b were
      examined in a western blot analysis. Results showed that MiR-106b expression was
      significantly inhibited in activated BMDCs upon OVA stimulation (p<0.05). Surface
      marker expression (e.g., MHC class II, CD80 and CD86) was significantly
      upregulated after the transfection of an miR-106b inhibitor (p<0.05), and the
      proportion of GATA-3(+) T cells was significantly increased among CD4(+) T cells
      that were cocultured with miR-106b inhibitor-pretreated BMDCs (p<0.05).
      Conversely, IL-12 production from OVA-activated BMDCs and the proportion of T
      bet(+) T cells increased significantly in a coculture of CD4(+) T cells and miR
      106b mimics-transfected BMDCs (p<0.05). The early growth response (Egr)-2 was
      identified via luciferase reporter assays as a target gene of miR-106b, and
      significant Egr-2 upregulation was observed in OVA-activated BMDCs following
      transfection with a miR-106b inhibitor (p<0.05). In conclusion, our results
      suggest that miR-106b negatively regulates the pro-allergic properties of BMDCs
      and subsequent Th2 polarisation upon OVA stimulation and might represent a
      promising therapeutic target for allergic inflammation. 

PMID- 25864618
TI  - iTreg induced from CD39(+) naive T cells demonstrate enhanced proliferate and
      suppressive ability.
AB  - CD4(+)CD25(+)FoxP3(+) regulatory T (Treg) cells which consist of naturally
      occurring Treg (nTreg) and induced Treg (iTreg) cells are associated with the
      maintenance of immune homeostasis. Previous studies were focused on their
      potential to ameliorate graft-versus-host disease (GVHD) in human and mice. CD39
      is a surface marker both expressed on CD4(+)CD25(-) T cells and Treg cells.
      CD39(+) Treg cells demonstrate stronger suppressive ability compared to
      conventional Treg cells. However, whether the potential of CD39(+) naive T cells
      induced Treg cells is different from conventional naive T cells induced Treg
      cells in vivo and vitro remains to be inconclusive. Here we demonstrate that
      CD39(+) iTreg cells show enhanced proliferation and suppressive ability as well
      as lower inflammatory cytokines compared to CD39(-) iTreg cells. To conclude, our
      findings demonstrate that CD39(+) iTreg cells acquire high suppressive capacity
      in vitro and vivo, and this may provide a new insight into Treg cell therapy in
      GVHD clinical trials. 

PMID- 25864619
TI  - Protection of acute GVHD by all-trans retinoic acid through suppression of T cell
      expansion and induction of regulatory T cells through IL-2 signaling.
AB  - All-trans retinoic acid (atRA), the active derivative of vitamin A, has been
      shown to regulate Treg and T effector cell differentiation. However, the
      potential use of atRA as a treatment for acute graft-verse-host disease (aGVHD)
      has not been realized. Here we studied the ability of atRA to prevent and treat
      acute-GVHD in the B6-to-F1(D2B6F1) murine model. Our results showed that atRA
      consistently displayed a potent ability to control aGVHD development and reduce
      mortality by suppressing the expansion of donor T cells and inhibiting cytokine
      expression from donor CD8 cells. Interestingly, CD4(+)Foxp3(+) regulatory T cells
      were markedly increased in the spleens of atRA-treated mice. In vitro treatment
      with atRA inhibited T cell proliferation in a dose-dependent manner. Injection of
      an anti-IL-2 antibody impaired the protection by atRA in aGVHD. Therefore, these
      results strongly implicate atRA as a novel therapeutic strategy for controlling
      aGVHD progression and treating other inflammatory diseases. 

PMID- 25864620
TI  - gammadelta T cells in infection and autoimmunity.
AB  - Standing at the interface of innate and adaptive immune, gammadelta T cells play
      important pathophysiologic roles in infection, autoimmunity, and tumorigenesis.
      Recent studies indicate that gammadelta T cells could be categorized into IFN
      gamma(+) and IL-17(+) subsets, both of which possess select TCR usages, bear
      unique surface markers and require different cytokine signaling to maintain the
      homeostasis. In addition, as the major innate IL-17 producers, gammadelta T cells
      are increasingly appreciated for their involvement in various acute infections
      and injuries. This review will summarize the characteristics of IFN-gamma(+)
      (gammadelta T-IFN-gamma) and IL-17(+) gammadelta T cells (gammadeltaT17) and
      discuss their distinct pathogenic functions in different disease models. 

PMID- 25864621
TI  - Molecular control of CD4(+) T cell lineage plasticity and integrity.
AB  - CD4(+) helper T cells and CD8(+) cytotoxic T cells form the two major subsets of
      peripheral T lymphocytes. Helper T cells fulfill crucial roles in the activation
      and coordination of the immune response, while cytotoxic T cells kill virus
      infected or tumor cells. Recent data suggest that the lineage identify of helper
      T cells is not fixed and that CD4(+) T cells under certain physiological
      conditions can be reprogrammed to express CD8 lineage genes and to develop into
      intestinal intraepithelial CD4(+) cytotoxic T lymphocytes that lack the
      expression of the key helper T cell lineage commitment factor ThPOK. Moreover,
      the analysis of mice with a conditional deletion of the transcription factor
      ThPOK or the histone deacetylases HDAC1 and HDAC2 indicated that CD8 lineage
      genes are actively repressed in CD4(+) T cells in order to maintain the lineage
      integrity of helper T cells. In this review I summarize recent studies that
      indicate plasticity of CD4(+) T cells towards a CTL program and that demonstrate
      that ThPOK and HDAC1-HDAC2 are part of a transcriptional regulatory circuit that
      counteracts the activity of the transcription factor Runx3 to maintain CD4(+) T
      cell lineage integrity. 

PMID- 25864622
TI  - IL-25 promotes the function of CD4+CD25+ T regulatory cells and prolongs skin
      graft survival in murine models.
AB  - Interleukin (IL)-25, also known as IL-17E, belongs to the IL-17 family of
      cytokines. Unlike other IL-17 family members, IL-25 promotes Th2-type immune
      responses, stimulating IL-4, IL-5, and IL-13 production. Here, we employed murine
      models of skin graft to explore the role of IL-25 in suppression of graft
      rejection. We found that IL-25 expression is increased during allograft
      rejection, and allograft rejection was enhanced in IL-25 KO mice. IL-25 KO was
      associated with down-regulation of Foxp3 expression in CD4+ T cells. Further,
      while adoptive transfer of WT regulatory T cells (Tregs) protected against
      allograft rejection, adoptive transfer of IL-25 deficient Tregs failed to protect
      against allograft rejection. Exogenous IL-25 restored Foxp3 expression and Treg
      function in vitro. Moreover, IL-25 promoted phosphorylation of NFAT2. Thus, IL-25
      may enhance Treg function by up-regulating NFAT2 phosphorylation. Our findings
      suggest that IL-25 can sustain Foxp3 expression, enhance the suppressive function
      of Tregs, and prolong skin-graft survival. 

PMID- 25864623
TI  - Update on the Vitamin D and OmegA-3 trial (VITAL).
AB  - Despite continued appreciation of the potential role of vitamin D and omega-3
      fatty acids in the prevention of cancer and cardiovascular disease (CVD), there
      remain no completed large-scale, randomized trials of these agents for the
      primary prevention of cancer or CVD in a population that has not been selected on
      the basis of elevated risk. The VITamin D and OmegA-3 TriaL (VITAL) is a 2*2
      factorial randomized, double-blind, placebo-controlled trial of the benefits and
      risks of vitamin D (vitamin D3 [cholecalciferol], 2000 IU/d) and marine omega-3
      fatty acids (Omacor((r)) fish oil, a 1 g/d) in the primary prevention of cancer
      and CVD among 25,875 men and women, aged >=50 and >=55 years, respectively.
      Randomization began in November 2011 and was completed in March 2014. This report
      will describe the rationale for the trial and currently available randomized
      trial data, summarize related ongoing large-scale trials, and provide a brief
      overview of study design, and an update on randomization milestones,
      racial/ethnic diversity, biorepository activities, in-depth phenotyping of a
      subcohort, and ancillary studies.

PMID- 25864624
TI  - Androgens induce sebaceous differentiation in sebocyte cells expressing a stable
      functional androgen receptor.
AB  - Androgens act through non-genomic and androgen receptor (AR)-dependent genomic
      mechanisms. AR is expressed in the sebaceous gland and the importance of
      androgens in the sebaceous function is well established. However, the in vitro
      models used to date have failed to evidence a clear genomic effect (e.g.,
      modification of gene expression profile) of androgens on human sebocyte cells. In
      order to study the impact of active androgens in sebocytes, we constructed a
      stable human sebocyte cell line derived from SEBO662 [17] constitutively
      expressing a fully functional AR. In these SEBO662 AR+ cells, dihydrotestosterone
      (DHT) induced AR nuclear translocation and the strong modulation of a set of
      transcripts (RASD1, GREB1...) known to be androgen-sensitive in other androgenic
      cells and tissues. Moreover, we observed that DHT precociously down-regulated
      markers for immature follicular cells (KRT15, TNC) and for hair lineage (KRT75,
      FST) and up-regulated the expression of genes potentially related to sebocyte
      differentiation (MUC1/EMA, AQP3, FADS2). These effects were fully confirmed at
      the protein level. In addition, DHT-stimulated SEBO662 AR+, cultured in a low
      calcium defined keratinocyte medium without serum or any complement,
      neosynthesize lipids, including sebum lipids, and store increased amounts of
      triglycerides in lipid droplets. DHT also induces morphological changes,
      increases cell size, and treatments over 7 days lead to a time-dependent increase
      in the population of apoptotic DNA-fragmented cells. Taken together, these
      results show for the first time that active androgens alone can engage immature
      sebocytes in a clear lipogenic differentiation process (Graphical abstract).
      These effects depend on the expression of a functional AR in these cells. This
      model should be of interest for revisiting the mechanisms of the sebaceous
      function in vitro and for the design of relevant pharmacological models for drug
      or compound testing.

PMID- 25864625
TI  - Daucosterol protects neurons against oxygen-glucose deprivation/reperfusion
      mediated injury by activating IGF1 signaling pathway.
AB  - We previously reported that daucosterol (a sterolin) up-regulates the expression
      of insulin-like growth factor I (IGF1)(1) protein in neural stem cells. In this
      study, we investigated the effects of daucosterol on the survival of cultured
      cortical neurons after neurons were subjected to oxygen and glucose deprivation
      and simulated reperfusion (OGD/R)(2), and determined the corresponding molecular
      mechanism. The results showed that post-treatment of daucosterol significantly
      reduced neuronal loss, as well as apoptotic rate and caspase-3 activity,
      displaying the neuroprotective activity. We also found that daucosterol increased
      the expression level of IGF1 protein, diminished the down-regulation of p-AKT(3)
      and p-GSK-3beta(4), thus activating the AKT(5) signal pathway. Additionally, it
      diminished the down-regulation of the anti-apoptotic proteins Mcl-1(6) and Bcl
      2(7), and decreased the expression level of the pro-apoptotic protein Bax(8),
      thus raising the ratio of Bcl-2/Bax. The neuroprotective effect of daucosterol
      was inhibited in the presence of picropodophyllin (PPP)(9), the inhibitor of
      insulin-like growth factor I receptors (IGF1R)(10). Our study provided
      information about daucosterol as an efficient and inexpensive neuroprotectants,
      to which the IGF1-like activity of daucosterol contributes. Daucosterol could be
      potentially developed as a medicine for ischemic stroke treatment.

PMID- 25864626
TI  - Cloud cover-adjusted ultraviolet B irradiance and pancreatic cancer incidence in
      172 countries.
AB  - BACKGROUND: Controversy exists regarding whether vitamin D deficiency could
      influence the etiology of pancreatic cancer. Several cohort studies have found
      that high serum 25-hydroxyvitamin D [25(OH)D] concentrations are associated with
      low risk of pancreatic cancer, while others have not. HYPOTHESIS: Low ultraviolet
      B irradiance is associated with high incidence of pancreatic cancer. METHODS: Age
      standardized pancreatic cancer incidence rates were obtained from GLOBOCAN in
      2008. The association between cloud-adjusted UVB irradiance and age-standardized
      incidence rates of pancreatic cancer was analyzed using regression. RESULTS:
      Overall, the lower the cloud-adjusted UVB irradiance, the higher the incidence
      rate of pancreatic cancer. Residents of countries with low UVB irradiance had
      approximately 6 times the incidence rates as those in countries with high UVB
      irradiance (p<0.0001 for males and p<0.0001 for females). This association
      persisted after adjustment for traditional risk factors of pancreatic cancer
      (p=0.0182 for males and p=0.0029 for females). CONCLUSIONS: There was an inverse
      association of cloud-adjusted UVB irradiance with incidence of pancreatic cancer
      that persisted after adjustment. This result is consistent with an inverse
      association of overall vitamin D deficiency in countries with lower UVB
      irradiance with risk of pancreatic cancer. Further research on the role of
      25(OH)D in reduction of pancreatic cancer in individuals would be desirable to
      expand the limited avenues available for prevention of this highly fatal disease.
      This article is part of a Special Issue entitled '17th Vitamin D Workshop'.

PMID- 25864628
TI  - Humeral torsion and throwing proficiency in early human evolution.

PMID- 25864627
TI  - Effects of 1alpha,25-(OH)2D3 on the formation and activity of osteoclasts in
      RAW264.7 cells.
AB  - The hormonally active form of vitamin D3, 1alpha,25-(OH)2D3, has an important
      role in bone metabolism. This study examined the effects of 1alpha,25-(OH)2D3 on
      the ability of two cytokines, receptor activator of nuclear factor-kappaB ligand
      (RANKL) and macrophage-colony stimulating factor (M-CSF), to induce RAW 264.7
      cells to form osteoclasts. A TRAP histochemical staining assay and bone
      resorption analysis were used to identify the rate of formation and activity of
      osteoclasts. The numbers of osteoclasts formed, and their bone resorption
      activity, was enhanced by the addition of 1alpha,25-(OH)2D3. The expression
      levels of osteoclast-specific proteins that are essential for bone resorption,
      integrin beta3, V-ATPase, CAII, CTSK, TRAP and MMP-9, were detected by western
      blotting. During 48 h, the expression levels of all these proteins significantly
      increased. Quantitative real-time polymerase chain reaction was used to determine
      the expression levels of the transcription factors, c-Fos and NFATcl. The
      expression levels of c-Fos and NFATc1 also increased 24h after treatment with
      1alpha,25-(OH)2D3. These results suggest that 1alpha,25-(OH)2D3 can regulate bone
      metabolism by directly enhancing the formation and maturation of osteoclasts.

PMID- 25864629
TI  - Tuning the mesomorphic properties of phenoxy-terminated smectic liquid crystals:
      the effect of fluoro substitution.
AB  - The mesomorphic properties of phenoxy-terminated 5-alkoxy-2-(4
      alkoxyphenyl)pyrimidine liquid crystals can be tuned in a predictable fashion
      with fluoro substituents on the phenoxy end-group. We show that an ortho-fluoro
      substituent promotes the formation of a tilted smectic C (SmC) phase whereas a
      para-fluoro substituent promotes the formation of an orthogonal smectic A (SmA)
      phase. The balance between SmA and SmC phases may be understood in terms of the
      energetic preference of the phenoxy end-groups to self-assemble via arene-arene
      interactions in a parallel or antiparallel geometry, and how these non-covalent
      interactions may cause either a suppression or enhancement of out-of-layer
      fluctuations at the interface of smectic layers. Calculations of changes in the
      potential energy of association DeltaE for non-covalent dimers of fluoro
      substituted n-butyloxybenzene molecules in parallel and antiparallel geometries
      support this hypothesis. We also show how mesomorphic properties can be further
      tuned by difluoro and perfluoro substitution, including difluoro substitution at
      the ortho positions, which uniquely promotes the formation of a SmC-nematic phase
      sequence. 

PMID- 25864630
TI  - Safety and efficacy of oral direct inhibitors of thrombin and factor Xa in
      antiphospholipid syndrome.
AB  - BACKGROUND: Long-term anticoagulation is recommended in antiphospholipid syndrome
      with thrombosis in order to prevent recurrences. While the current mainstay
      relies on vitamin K antagonists, their long-term maintenance may remain
      challenging. OBJECTIVES: To report on the safety and the efficacy of oral direct
      inhibitors of thrombin and factor Xa (ODIs) in antiphospholipid syndrome (APS).
      METHODS: We performed a descriptive analysis of patients with APS enrolled in a
      French multicentre observational cohort between January 2012 and March 2014 and
      receiving ODIs. The main outcomes were the occurrence of a thrombotic recurrence
      or bleeding events. RESULTS: Twenty-six patients with APS (primary in 12)
      received ODIs. Twenty patients had been previously treated with VKA (n=19), or
      fondaparinux (n=1) for a median duration of 3years. ODIs were introduced as
      second-line therapy because of INR lability/therapeutic simplification (n=17),
      recurrent thrombosis (n=1), VKA's associated bleeding event (n=1), and atrial
      fibrillation (n=1). Six patients received ODIs as first-line therapy. After a
      median [IQR] follow-up of 19 [8-29] months, one relapse of arterial thrombosis,
      two bleeding events (hypermenorrhea and rectal bleeding under rivaroxaban) and
      one recurrent migraine were reported, leading to discontinuation of therapy in
      these 4 patients. CONCLUSION: ODIs might be an alternative therapeutic option in
      APS. Prospective studies are warranted to evaluate their safety in this
      condition.

PMID- 25864631
TI  - Structural basis of arc binding to synaptic proteins: implications for cognitive
      disease.
AB  - Arc is a cellular immediate-early gene (IEG) that functions at excitatory
      synapses and is required for learning and memory. We report crystal structures of
      Arc subdomains that form a bi-lobar architecture remarkably similar to the capsid
      domain of human immunodeficiency virus (HIV) gag protein. Analysis indicates Arc
      originated from the Ty3/Gypsy retrotransposon family and was "domesticated" in
      higher vertebrates for synaptic functions. The Arc N-terminal lobe evolved a
      unique hydrophobic pocket that mediates intermolecular binding with synaptic
      proteins as resolved in complexes with TARPgamma2 (Stargazin) and CaMKII peptides
      and is essential for Arc's synaptic function. A consensus sequence for Arc
      binding identifies several additional partners that include genes implicated in
      schizophrenia. Arc N-lobe binding is inhibited by small chemicals suggesting
      Arc's synaptic action may be druggable. These studies reveal the remarkable
      evolutionary origin of Arc and provide a structural basis for understanding Arc's
      contribution to neural plasticity and disease. 

PMID- 25864632
TI  - Multimodal Interactions between Proprioceptive and Cutaneous Signals in Primary
      Somatosensory Cortex.
AB  - The classical view of somatosensory processing holds that proprioceptive and
      cutaneous inputs are conveyed to cortex through segregated channels, initially
      synapsing in modality-specific areas 3a (proprioception) and 3b (cutaneous) of
      primary somatosensory cortex (SI). These areas relay their signals to areas 1 and
      2 where multimodal convergence first emerges. However, proprioceptive and
      cutaneous maps have traditionally been characterized using unreliable stimulation
      tools. Here, we employed a mechanical stimulator that reliably positioned
      animals' hands in different postures and presented tactile stimuli with superb
      precision. Single-unit recordings in SI revealed that most neurons responded to
      cutaneous and proprioceptive stimuli, including cells in areas 3a and 3b.
      Multimodal responses were characterized by linear and nonlinear effects that
      emerged during early (~20 ms) and latter (> 100 ms) stages of stimulus
      processing, respectively. These data are incompatible with the modality
      specificity model in SI, and provide evidence for distinct mechanisms of
      multimodal processing in the somatosensory system.

PMID- 25864633
TI  - Neural Mechanisms for Evaluating Environmental Variability in Caenorhabditis
      elegans.
AB  - The ability to evaluate variability in the environment is vital for making
      optimal behavioral decisions. Here we show that Caenorhabditis elegans evaluates
      variability in its food environment and modifies its future behavior accordingly.
      We derive a behavioral model that reveals a critical period over which
      information about the food environment is acquired and predicts future search
      behavior. We also identify a pair of high-threshold sensory neurons that encode
      variability in food concentration and the downstream dopamine-dependent circuit
      that generates appropriate search behavior upon removal from food. Further, we
      show that CREB is required in a subset of interneurons and determines the
      timescale over which the variability is integrated. Interestingly, the
      variability circuit is a subset of a larger circuit driving search behavior,
      showing that learning directly modifies the very same neurons driving behavior.
      Our study reveals how a neural circuit decodes environmental variability to
      generate contextually appropriate decisions.

PMID- 25864634
TI  - Neural mechanisms underlying human consensus decision-making.
AB  - Consensus building in a group is a hallmark of animal societies, yet little is
      known about its underlying computational and neural mechanisms. Here, we applied
      a computational framework to behavioral and fMRI data from human participants
      performing a consensus decision-making task with up to five other participants.
      We found that participants reached consensus decisions through integrating their
      own preferences with information about the majority group members' prior choices,
      as well as inferences about how much each option was stuck to by the other
      people. These distinct decision variables were separately encoded in distinct
      brain areas-the ventromedial prefrontal cortex, posterior superior temporal
      sulcus/temporoparietal junction, and intraparietal sulcus-and were integrated in
      the dorsal anterior cingulate cortex. Our findings provide support for a
      theoretical account in which collective decisions are made through integrating
      multiple types of inference about oneself, others, and environments, processed in
      distinct brain modules.

PMID- 25864635
TI  - Different functional neural substrates for good and poor language outcome in
      autism.
AB  - Autism (ASD) is vastly heterogeneous, particularly in early language development.
      While ASD language trajectories in the first years of life are highly unstable,
      by early childhood these trajectories stabilize and are predictive of longer-term
      outcome. Early neural substrates that predict/precede such outcomes are largely
      unknown, but could have considerable translational and clinical impact. Pre
      diagnosis fMRI response to speech in ASD toddlers with relatively good language
      outcome was highly similar to non-ASD comparison groups and robustly recruited
      language-sensitive superior temporal cortices. In contrast, language-sensitive
      superior temporal cortices were hypoactive in ASD toddlers with poor language
      outcome. Brain-behavioral relationships were atypically reversed in ASD, and a
      multimodal combination of pre-diagnostic clinical behavioral measures and speech
      related fMRI response showed the most promise as an ASD prognosis classifier.
      Thus, before ASD diagnoses and outcome become clinically clear, distinct
      functional neuroimaging phenotypes are already present that can shed insight on
      an ASD toddler's later outcome. VIDEO ABSTRACT.

PMID- 25864636
TI  - Activity of defined mushroom body output neurons underlies learned olfactory
      behavior in Drosophila.
AB  - During olfactory learning in fruit flies, dopaminergic neurons assign value to
      odor representations in the mushroom body Kenyon cells. Here we identify a class
      of downstream glutamatergic mushroom body output neurons (MBONs) called M4/6, or
      MBON-beta2beta'2a, MBON-beta'2mp, and MBON-gamma5beta'2a, whose dendritic fields
      overlap with dopaminergic neuron projections in the tips of the beta, beta', and
      gamma lobes. This anatomy and their odor tuning suggests that M4/6 neurons pool
      odor-driven Kenyon cell synaptic outputs. Like that of mushroom body neurons,
      M4/6 output is required for expression of appetitive and aversive memory
      performance. Moreover, appetitive and aversive olfactory conditioning
      bidirectionally alters the relative odor-drive of M4beta' neurons (MBON
      beta'2mp). Direct block of M4/6 neurons in naive flies mimics appetitive
      conditioning, being sufficient to convert odor-driven avoidance into approach,
      while optogenetically activating these neurons induces avoidance behavior. We
      therefore propose that drive to the M4/6 neurons reflects odor-directed
      behavioral choice. 

PMID- 25864638
TI  - Epidemiology of bacterial meningitis in the North American Arctic, 2000-2010.
AB  - OBJECTIVE: To determine the incidence of meningitis caused by Haemophilus
      influenzae, Neisseria meningitidis, and Streptococcus pneumoniae in the North
      American Arctic during 2000-2010. METHODS: Surveillance data were obtained from
      the International Circumpolar Surveillance network. We defined a case of
      bacterial meningitis caused by H. influenzae, N. meningitidis, or S. pneumoniae
      as a culture-positive isolate obtained from a normally sterile site in a resident
      with a meningitis diagnosis. RESULTS: The annual incidence/100,000 persons for
      meningitis caused by H. influenzae, N. meningitidis, and S. pneumoniae among all
      North American Arctic residents was: 0.6, 0.5, and 1.5, respectively; the
      meningitis incidence among indigenous persons in Alaska and Canada (indigenous
      status not recorded in Greenland) for those three bacteria was: 2.1, 0.8, and
      2.4, respectively. The percentage of pneumococcal isolates belonging to a 7
      valent pneumococcal conjugate vaccine serotype declined from 2000-2004 to 2005
      2010 (31%-2%, p-value <0.01). During 2005-2010, serotype a caused 55% of H.
      influenzae meningitis and serogroup B caused 86% of meningococcal meningitis.
      CONCLUSIONS: Compared with all North American Arctic residents, indigenous people
      suffer disproportionately from bacterial meningitis. Arctic residents could
      benefit from the development of an H. influenzae serotype a vaccine and
      implementation of a meningococcal serogroup B vaccine.

PMID- 25864637
TI  - Specification of select hypothalamic circuits and innate behaviors by the
      embryonic patterning gene dbx1.
AB  - The hypothalamus integrates information required for the production of a variety
      of innate behaviors such as feeding, mating, aggression, and predator avoidance.
      Despite an extensive knowledge of hypothalamic function, how embryonic genetic
      programs specify circuits that regulate these behaviors remains unknown. Here, we
      find that in the hypothalamus the developmentally regulated homeodomain
      containing transcription factor Dbx1 is required for the generation of specific
      subclasses of neurons within the lateral hypothalamic area/zona incerta (LH) and
      the arcuate (Arc) nucleus. Consistent with this specific developmental role, Dbx1
      hypothalamic-specific conditional-knockout mice display attenuated responses to
      predator odor and feeding stressors but do not display deficits in other innate
      behaviors such as mating or conspecific aggression. Thus, activity of a single
      developmentally regulated gene, Dbx1, is a shared requirement for the
      specification of hypothalamic nuclei governing a subset of innate behaviors.
      VIDEO ABSTRACT. 

PMID- 25864640
TI  - The human gut microbiome, a taxonomic conundrum.
AB  - From culture to metagenomics, within only 130 years, our knowledge of the human
      microbiome has considerably improved. With >1000 microbial species identified to
      date, the gastro-intestinal microbiota is the most complex of human biotas. It is
      composed of a majority of Bacteroidetes and Firmicutes and, although exhibiting
      great inter-individual variations according to age, geographic origin, disease or
      antibiotic uptake, it is stable over time. Metagenomic studies have suggested
      associations between specific gut microbiota compositions and a variety of
      diseases, including irritable bowel syndrome, Crohn's disease, colon cancer, type
      2 diabetes and obesity. However, these data remain method-dependent, as no
      consensus strategy has been defined to decipher the complexity of the gut
      microbiota. High-throughput culture-independent techniques have highlighted the
      limitations of culture by showing the importance of uncultured species, whereas
      modern culture methods have demonstrated that metagenomics underestimates the
      microbial diversity by ignoring minor populations. In this review, we highlight
      the progress and challenges that pave the way to a complete understanding of the
      human gastrointestinal microbiota and its influence on human health. 

PMID- 25864641
TI  - Evaluation of anhedonia with the Snaith-Hamilton Pleasure Scale (SHAPS) in adult
      outpatients with major depressive disorder.
AB  - Anhedonia or inability to experience pleasure not only is a core symptom of major
      depressive disorder (MDD), but also is identified as an important component of
      the positive valence system in the NIMH Research Domain Criteria. The Snaith
      Hamilton Pleasure Scale (SHAPS) has been developed for the assessment of hedonic
      experience or positive valence, but has not been well-studied in depressed
      outpatient populations. The current study examined the reliability and validity
      of the SHAPS using a sample of adult outpatients with treatment resistant MDD.
      Data for the current study were obtained from 122 adult outpatients with a
      diagnosis of MDD and non-response to adequate treatment with an SSRI and who
      participated in Project TReatment with Exercise Augmentation for Depression
      (TREAD). A Principal Components Analysis was used to define the dimensionality of
      the SHAPS. Convergent and discriminant validity were evaluated via correlations
      of the SHAPS total score with "gold standard" measures of depression severity and
      quality of life. The SHAPS was found to have high internal consistency
      (Cronbach's coefficient alpha = .82). A Principal Components Analysis suggests
      that the SHAPS is mainly "unidimensional" and limited to hedonic experience among
      adult outpatients with MDD. Convergent and discriminant validity were assessed by
      examining the Spearman rank-order correlation coefficient between the SHAPS total
      score and the HRSD17 (rs = 0.22, p < .03), IDS-C30 (rs = 0.26, p < .01), IDS-SR30
      (rs = 0.23, p < .02), QIDS-C16 (rs = 0.22, p < .03), QIDS-SR16 (rs = 0.17, p <
      .10), QLES-Q (rs = -0.32, p < .002), and the pleasure/enjoyment item (sub-item
      21) of the IDS-C (rs = 0.44, p < .0001) and IDS-SR (rs = 0.38, p < .0002). The
      self-administered SHAPS showed modest sensitivity (76%) and specificity (54%)
      with the self-administered pleasure/enjoyment single item (sub-item 21) of IDS
      SR30. The current study shows that the SHAPS is a reliable and valid instrument
      to assess hedonic experience or positive valence in adult outpatients with MDD
      and provides a broader assessment of this important domain. 

PMID- 25864642
TI  - Direct electron injection into an oxide insulator using a cathode buffer layer.
AB  - Injecting charge carriers into the mobile bands of an inorganic oxide insulator
      (for example, SiO2, HfO2) is a highly complicated task, or even impossible
      without external energy sources such as photons. This is because oxide insulators
      exhibit very low electron affinity and high ionization energy levels. Here we
      show that a ZnO layer acting as a cathode buffer layer permits direct electron
      injection into the conduction bands of various oxide insulators (for example,
      SiO2, Ta2O5, HfO2, Al2O3) from a metal cathode. Studies of current-voltage
      characteristics reveal that the current ohmically passes through the ZnO/oxide
      insulator interface. Our findings suggests that the oxide insulators could be
      used for simply fabricated, transparent and highly stable electronic valves. With
      this strategy, we demonstrate an electrostatic discharging diode that uses 100-nm
      SiO2 as an active layer exhibiting an on/off ratio of ~10(7), and protects the
      ZnO thin-film transistors from high electrical stresses. 

PMID- 25864643
TI  - Interference of GSM mobile phones with communication between Cardiac Rhythm
      Management devices and programmers: A combined in vivo and in vitro study.
AB  - To investigate interference, and how to avoid it, by high-frequency
      electromagnetic fields (EMFs) of Global System for Mobile Communications (GSM)
      mobile phone with communication between cardiac rhythm management devices (CRMs)
      and programmers, a combined in vivo and in vitro testing was conducted. During in
      vivo testing, GSM mobile phones interfered with CRM-programmer communication in
      33 of 65 subjects tested (50.8%). Losing ventricle sensing was representative in
      this study. In terms of clinical symptoms, only 4 subjects (0.6%) felt dizzy
      during testing. CRM-programmer communication recovered upon termination of mobile
      phone communication. During in vitro testing, electromagnetic interference by
      high-frequency (700-950 MHz) EMFs reproducibly occurred in duplicate testing in
      18 of 20 CRMs (90%). During each interference, the pacing pulse signal on the
      programmer would suddenly disappear while the synchronous signal was normal on
      the amplifier-oscilloscope. Simulation analysis showed that interference by
      radiofrequency emitting devices with CRM-programmer communication may be
      attributed to factors including materials, excitation source distance, and
      implant depth. Results suggested that patients implanted with CRMs should not be
      restricted from using GSM mobile phones; however, CRMs should be kept away from
      high-frequency EMFs of GSM mobile phone during programming.

PMID- 25864644
TI  - CD44 knock-down in bovine and human chondrocytes results in release of bound
      HYAL2.
AB  - CD44 shedding occurs in osteoarthritic chondrocytes. Previous work of others has
      suggested that the hyaluronidase isoform HYAL2 has the capacity to bind to CD44,
      a binding that may itself induce CD44 cleavage. Experiments were developed to
      elucidate whether chondrocyte HYAL2: (1) was exposed on the extracellular plasma
      membrane of chondrocytes, (2) bound to CD44, (3) underwent shedding together with
      CD44 and lastly, (4) exhibited hyaluronidase activity within a near-neutral pH
      range. Enhancing CD44 shedding by IL-1beta resulted in a proportional increase in
      HYAL2 released from human and bovine chondrocytes into the medium. CD44 knockdown
      by siRNA also resulted in increased accumulation of HYAL2 in the media of
      chondrocytes. By hyaluronan zymography only activity at pH3.7 was observed and
      this activity was reduced by pre-treatment of chondrocytes with trypsin. CD44 and
      HYAL2 were found to co-immunoprecipitate, and to co-localize within intracellular
      vesicles and at the plasma membrane. Degradation of hyaluronan was visualized by
      agarose gel electrophoresis. With this approach, hyaluronidase activity could be
      observed at pH4.8 under assay conditions in which CD44 and HYAL2 binding remained
      intact; additionally, weak hyaluronidase activity could be observed at pH6.8
      under these conditions. This study suggests that CD44 and HYAL2 are bound at the
      surface of chondrocytes. The release of HYAL2 when CD44 is shed could provide a
      mechanism for weak hyaluronidase activity to occur within the more distant
      extracellular matrix of cartilage. 

PMID- 25864645
TI  - The cortisol response to social stress in social anxiety disorder.
AB  - This study evaluated the cortisol stress response (CSR) following the Trier
      Social Stress Test in Social Anxiety Disorder (SAD) and control participants, to
      determine whether individual differences in CSR associate more with SAD diagnosis
      or dimensional characteristics [i.e. childhood trauma (CT)]. Twenty-one
      participants (11 with SAD) had full data available for both CT-scores and
      cortisol area-under-the-curve (AUC). Linear regression produced significant
      results: predicting AUCG with study group, emotional abuse (EA) scores and their
      interaction (F=3.14, df=5,15; p=.039); of note, the study group by EA interaction
      was significant at p=.015, driven by a strong positive association between EA and
      cortisol AUCG in the control group, and a negative association between these
      variables in the SAD group (standardized-beta=1.56, t=2.75, p=.015). This
      suggests that EA in SAD patients is associated with altered CSR, highlighting
      need to measure dimensional characteristics. 

PMID- 25864639
TI  - Genetic divergence and gene flow among Mesorhizobium strains nodulating the shrub
      legume Caragana.
AB  - Although the biogeography of rhizobia has been investigated extensively, little
      is known about the adaptive molecular evolution of rhizobia influenced by soil
      environments and selected by legumes. In this study, microevolution of
      Mesorhizobium strains nodulating Caragana in a semi-fixing desert belt in
      northern China was investigated. Five core genes-atpD, glnII, gyrB, recA, and
      rpoB, six heat-shock factor genes-clpA, clpB, dnaK, dnaJ, grpE, and hlsU, and
      five nodulation genes-nodA, nodC, nodD, nodG, and nodP, of 72 representative
      mesorhizobia were studied in order to determine their genetic variations. A total
      of 21 genospecies were defined based on the average nucleotide identity (ANI) of
      concatenated core genes using a threshold of 96% similarity, and by the
      phylogenetic analyses of the core/heat-shock factor genes. Significant genetic
      divergence was observed among the genospecies in the semi-fixing desert belt
      (areas A-E) and Yunnan province (area F), which was closely related to the
      environmental conditions and geographic distance. Gene flow occurred more
      frequently among the genospecies in areas A-E, and three sites in area B, than
      between area F and the other five areas. Recombination occurred among strains
      more frequently for heat-shock factor genes than the other genes. The results
      conclusively showed that the Caragana-associated mesorhizobia had divergently
      evolved according to their geographic distribution, and have been selected not
      only by the environmental conditions but also by the host plants. 

PMID- 25864646
TI  - Diverse array-designed modes of combination therapies in Fangjiomics.
AB  - In line with the complexity of disease networks, diverse combination therapies
      have been demonstrated potential in the treatment of different patients with
      complex diseases in a personal combination profile. However, the identification
      of rational, compatible and effective drug combinations remains an ongoing
      challenge. Based on a holistic theory integrated with reductionism, Fangjiomics
      systematically develops multiple modes of array-designed combination therapies.
      We define diverse "magic shotgun" vertical, horizontal, focusing, siege and
      dynamic arrays according to different spatiotemporal distributions of hits on
      targets, pathways and networks. Through these multiple adaptive modes for
      treating complex diseases, Fangjiomics may help to identify rational drug
      combinations with synergistic or additive efficacy but reduced adverse side
      effects that reverse complex diseases by reconstructing or rewiring multiple
      targets, pathways and networks. Such a novel paradigm for combination therapies
      may allow us to achieve more precise treatments by developing phenotype-driven
      quantitative multi-scale modeling for rational drug combinations. 

PMID- 25864647
TI  - Triptolide inhibits human breast cancer MCF-7 cell growth via downregulation of
      the ERalpha-mediated signaling pathway.
AB  - AIM: To investigate the anticancer mechanisms of triptolide, a diterpenoid
      isolated from the plant Tripterygium wilfordii Hook F, against human breast
      cancer cells and the involvement of the estrogen receptor-alpha (ERalpha)
      mediated signaling pathway in particular. METHODS: Human breast cancer ERalpha
      positive MCF-7 cells and ERalpha-negative MDA-MB-231 cells were tested.
      PrestoBlue assay was used to evaluate the cell viability. The levels of ERalpha
      mRNA and protein were detected with real-time PCR and immunoblotting,
      respectively. Mouse models of MCF-7 or MDA-MB-231 xenograft tumors were treated
      with triptolide (0.4 mg.kg(-1).d(-1), po) or a selective estrogen receptor
      modulator tamoxifen (mg.kg(-1).d(-1), po) for 3 weeks, and the tumor weight and
      volume were measured. RESULTS: Triptolide (5-200 nmol/L) dose-dependently
      inhibited the viability of both MCF-7 and MDA-MB-231 cells, with a more potent
      inhibition on MCF-7 cells. Knockdown of ERalpha in MCF-7 cells by siRNA
      significantly attenuated the cytotoxicity of triptolide, whereas overexpression
      of ERalpha in MDA-MB-231 cells markedly enhanced the cytotoxicity. Triptolide
      dose-dependently decreased the expression of ERalpha in MCF-7 cells and MCF-7
      xenograft tumors. Furthermore, treatment of MCF-7 cells with triptolide inhibited
      the phosphorylation of ERK1/2 in dose- and time-dependent manners. In the mice
      xenografted with MCF-7 cells, treatment with triptolide or tamoxifen resulted in
      significant reduction in the tumor weight and volume. Similar effects were not
      obtained in the mice xenografted with MDA-MB-231 cells. CONCLUSION: The
      anticancer activity of triptolide against ERalpha-positive human breast cancer is
      partially mediated by downregulation of the ERalpha-mediated signaling pathway.

PMID- 25864648
TI  - Fructus phyllanthi tannin fraction induces apoptosis and inhibits migration and
      invasion of human lung squamous carcinoma cells in vitro via MAPK/MMP pathways.
AB  - AIM: Fructus phyllanthi tannin fraction (PTF) from the traditional Tibetan
      medicine Fructus phyllanthi has been found to inhibit lung and liver carcinoma in
      mice. In this study we investigated the anticancer mechanisms of PTF in human
      lung squamous carcinoma cells in vitro. METHODS: Human lung squamous carcinoma
      cell line (NCI-H1703), human large-cell lung cancer cell line (NCI-H460), human
      lung adenocarcinoma cell line (A549) and human fibrosarcoma cell line (HT1080)
      were tested. Cell viability was detected with MTT assay. Cell migration and
      invasion were assessed using a wound healing assay and a transwell chemotaxis
      chambers assay, respectively. Cell apoptosis was analyzed with flow cytometric
      analysis. The levels of apoptosis-related and metastasis-related proteins were
      detected by Western blot and immunofluorescence. RESULTS: PTF dose-dependently
      inhibited the viability of the 3 human lung cancer cells. The IC50 values of PTF
      in inhibition of NCI-H1703, NCI-H460, and A549 cells were 33, 203, and 94 mg/L,
      respectively. PTF (15, 30, and 60 mg/L) dose-dependently induced apoptosis of NCI
      H1703 cells. Treatment of NCI-H1703 and HT1080 cells with PTF significantly
      inhibited cell migration, and reduced the number of invasive cells through
      Matrigel. Furthermore, PTF dose-dependently down-regulated the expression of
      phosphor-ERK1/2, MMP-2 and MMP-9, up-regulated the expression of phosphor-JNK,
      but had no significant effect on the expression of ERK1/2 or JNK. CONCLUSION: PTF
      induces cell apoptosis and inhibits the migration and invasion of NCI-H1703 cells
      by decreasing MPPs expression through regulation of the MAPK pathway.

PMID- 25864650
TI  - Efficacy-oriented compatibility for component-based Chinese medicine.
AB  - Single-target drugs have not achieved satisfactory therapeutic effects for
      complex diseases involving multiple factors. Instead, innovations in recent drug
      research and development have revealed the emergence of compound drugs, such as
      cocktail therapies and "polypills", as the frontier in new drug development. A
      traditional Chinese medicine (TCM) prescription that is usually composed of
      several medicinal herbs can serve a typical representative of compound medicines.
      Although the traditional compatibility theory of TCM cannot be well expressed
      using modern scientific language nowadays, the fundamental purpose of TCM
      compatibility can be understood as promoting efficacy and reducing toxicity. This
      paper introduces the theory and methods of efficacy-oriented compatibility for
      developing component-based Chinese medicines. 

PMID- 25864649
TI  - Associations of UDP-glucuronosyltransferases polymorphisms with mycophenolate
      mofetil pharmacokinetics in Chinese renal transplant patients.
AB  - AIM: To evaluate the effects of UDP-glucuronosyltransferases (UGTs) polymorphisms
      on the pharmacokinetics of the immunosuppressant mycophenolate mofetil (MMF) in
      Chinese renal transplant recipients. METHODS: A total of 127 renal transplant
      patients receiving MMF were genotyped for polymorphisms in UGT1A9 -1818T>C,
      I399C>T, -118T9/10, -440C>T, -331T>C, UGT2B7 IVS1+985A>G, 211G>T, -900A>G, UGT1A8
      518C>G and UGT1A7 622T>C. The plasma concentrations of the MMF active moiety
      mycophenolic acid (MPA) and main metabolite 7-O-MPA-glucuronide (MPAG) were
      analyzed using HPLC. Univariate and multivariate analyses were used to assess the
      effects of UGT-related gene polymorphisms on MPA pharmacokinetics. RESULTS: The
      dose-adjusted MPA AUC0-12 h of the patients with the UGT2B7 IVS1+985AG genotype
      was 48% higher than that of the patients with the IVS1+985AA genotype, which
      could explain 11.2% of the inter-individual variation in MPA pharmacokinetics.
      The dose-adjusted MPAG AUC0-12 h of the patients with the UGT1A7 622CC and UGT1A9
      -440CT/-331TC genotypes, respectively, was significantly higher than that of the
      patients with 622T homozygotes and -440C/-331T homozygotes. Furthermore, the
      genotypes UGT1A9 -1818T>C and UGT1A8 518C>G were associated with a low dose
      adjusted MPAG AUC0-12 h. CONCLUSION: The UGT2B7 11+985A>G genotype is associated
      with the pharmacokinetics of MPA in Chinese renal transplant patients, which
      demonstrates the usefulness of this SNP for individualizing MMF dosing.

PMID- 25864651
TI  - Amiloride sensitizes human pancreatic cancer cells to erlotinib in vitro through
      inhibition of the PI3K/AKT signaling pathway.
AB  - AIM: Blockade of EGFR by EGFR tyrosine kinase inhibitors such as erlotinib is
      insufficient for effective treatment of human pancreatic cancer due to
      independent activation of the Akt pathway, while amiloride, a potassium-sparing
      diuretic, has been found as a potential Akt inhibitor. The aim of this study was
      to investigate the anticancer effects of combined amiloride with erlotinib
      against human pancreatic cancer cells in vitro. METHODS: Cell proliferation,
      colony formation, cell cycle and apoptosis were analyzed in 4 human pancreatic
      cancer cell lines Bxpc-3, PANC-1, Aspc-1 and CFPAC-1 treated with erlotinib or
      amiloride alone, or in their combination. The synergistic analysis for the
      effects of combinations of amiloride and erlotinib was performed using Chou
      Talalay's combination index isobolographic method. RESULTS: Amiloride (10, 30,
      and 100 MUmol/L) concentration-dependently potentiated erlotinib-induced
      inhibition of cell proliferation and colony formation in the 4 pancreatic cancer
      cell lines. Isobolographic analysis confirmed that combinations of amiloride and
      erlotinib produced synergistic cytotoxic effects. Amiloride significantly
      potentiated erlotinib-induced G0/G1 cell-cycle arrest and apoptosis in Bxpc-3 and
      PANC-1 cells. Amiloride inhibited EGF-stimulated phorsphorylation of AKT, and
      significantly enhanced erlotinib-induced downregulation of phorsphorylation of
      EGFR, AKT, PI3K P85 and GSK 3beta in Bxpc-3 and PANC-1 cells. CONCLUSION:
      Amiloride sensitizes human pancreatic cancer cells to erlotinib in vitro through
      inhibition of the PI3K/AKT signaling pathway. Treatment of pancreatic cancer
      patients with combination of erlotinib and amiloride merits further
      investigation.

PMID- 25864652
TI  - Echinacoside induces rat pulmonary artery vasorelaxation by opening the NO-cGMP
      PKG-BKCa channels and reducing intracellular Ca2+ levels.
AB  - AIM: Sustained pulmonary vasoconstriction as experienced at high altitude can
      lead to pulmonary hypertension (PH). The main purpose of this study is to
      investigate the vasorelaxant effect of echinacoside (ECH), a phenylethanoid
      glycoside from the Tibetan herb Lagotis brevituba Maxim and Cistanche tubulosa,
      on the pulmonary artery and its potential mechanism. METHODS: Pulmonary arterial
      rings obtained from male Wistar rats were suspended in organ chambers filled with
      Krebs-Henseleit solution, and isometric tension was measured using a force
      transducer. Intracellular Ca(2+) levels were measured in cultured rat pulmonary
      arterial smooth muscle cells (PASMCs) using Fluo 4-AM. RESULTS: ECH (30-300
      MUmol/L) relaxed rat pulmonary arteries precontracted by noradrenaline (NE) in a
      concentration-dependent manner, and this effect could be observed in both intact
      endothelium and endothelium-denuded rings, but with a significantly lower maximum
      response and a higher EC50 in endothelium-denuded rings. This effect was
      significantly blocked by L-NAME, TEA, and BaCl2. However, IMT, 4-AP, and Gli did
      not inhibit ECH-induced relaxation. Under extracellular Ca(2+)-free conditions,
      the maximum contraction was reduced to 24.54%+/-2.97% and 10.60%+/-2.07% in rings
      treated with 100 and 300 MUmol/L of ECH, respectively. Under extracellular
      calcium influx conditions, the maximum contraction was reduced to 112.42%+/
      7.30%, 100.29%+/-8.66%, and 74.74%+/-4.95% in rings treated with 30, 100, and 300
      MUmol/L of ECH, respectively. After cells were loaded with Fluo 4-AM, the mean
      fluorescence intensity was lower in cells treated with ECH (100 MUmol/L) than
      with NE. CONCLUSION: ECH suppresses NE-induced contraction of rat pulmonary
      artery via reducing intracellular Ca(2+) levels, and induces its relaxation
      through the NO-cGMP pathway and opening of K(+) channels (BKCa and KIR).

PMID- 25864653
TI  - [Intrinsic sphincter deficiency and female urinary incontinence].
AB  - OBJECTIVE: Stress urinary female incontinence (SUI) is primary due to intrinsic
      sphincter deficiency (ISD) and urethral hypermobility. Despite a lack of
      standardised international definition, ISD needs to be clearly diagnosed in order
      to be correctly treated. This work is an update about the female ISD produced
      from a review of a published article. MATERIAL AND METHODS: This review of
      article published on this subject in the Medline (Pubmed database), selected
      according to their scientific relevants, of consensus conferences and published
      guidelines, has been performed by the committee for women pelvic floor surgery of
      the French Urological Association. RESULTS: Although there is no international
      consensus definition, we can consider that the ISD is a composite concept
      combining urodynamic data (MUCP < 20 or 30 cmH20) and one or more clinical
      information (no urethral mobility, negative urethral support test, failure of a
      first surgery, leakage during abdominal straining, high stress incontinence
      scores). Imaging can provide additional evidence for intrinsic sphincter
      deficiency diagnosis, but the correlation between imaging and function remains
      low. By standardizing methodology and interpretations to better diagnose women
      with ISD, it may be possible to improve preoperative planning and outcomes for
      these patients. A retropubic midurethral sling can be performed as a first
      surgery. In case of a lack of urethral mobility, the artificial urinary sphincter
      (AUS) remains the gold standard. Adjustable continence therapy (ACT((r))) can be
      proposed as an alternative option. The efficacy and safety of muscle-derived cell
      therapy in ISD needs more studies. Injection of bulking agents may be an option
      according to the severity and the expectations of the patient. Bladder
      overactivity needs to be treated as first-line in case of mixed urinary
      incontinence. In elderly women, a careful evaluation of the bladder contractility
      and comorbidity must be performed. A geriatric evaluation can be necessary.
      CONCLUSION: Clinical and paraclinical assessment allow to confirm the diagnosis
      of female ISD, to estimate its severity, and to identify associated mechanisms of
      incontinence (urethral hypermobility, bladder overactivity) to choose the most
      adapted treatment.

PMID- 25864654
TI  - [Evolution aspect of anatomy clinical lesions of urogenital fistula (UGF) in
      Cocody Teaching Hospital urological unity from 1990 to 2011].
AB  - PURPOSE: The aim of this study is to compare anatomy pathological lesions seeing
      in urogenital fistula in Cocody Teaching Hospital between two decades, 1990 to
      2000 and 2000 to 2010. MATERIEL AND METHOD: This survey is retrospective and
      carries on 20 years (January 1990 to December 2011) 190 urogenital fistulas (140
      cases between 1990 and 1999; 50 from 2000 to 2011) hospitalized in our unity.
      Anatomy clinical characteristics of these fistulas were determined by clinical or
      paraclinical examination. RESULTS: Between 1990 and 1999, fistulas were
      classified in 20 bladder-uterine fistulas (14.29%), 16 uretro-vaginal fistulas
      (11.43%) and 104 bladder-vaginal fistulas (74.29%) of whom 80 isolated UGFs and
      24 UGFs associated with recto-vaginal fistula. These 104 UGFs were located at:
      bladder neck 22 cases (21.15%), bladder trigonal 46 cases (44.23%), urethra 14
      cases (13.46%). Twenty-two bladder sphincter were destroyed and represented
      21.15% of fistula's bladder-vaginal fistula and 15.71% of all UGFs. The average
      fistula diameter was 3 cm [extremes: 1 and 12 cm]. In 22 cases (15.71%), fistula
      diameter was more than 10 cm. It was bladder neck and sphincter destruction.
      Hundred and twenty-six fistulas were isolated (90%). Only 10% (14 cases) were
      associated. Fistulas were primitive in 85.71% of cases (120/140), recurrent in 7
      cases (7.86%) and multi-recurrent (>3 reinterventions) in 9 cases (6.43%). From
      2001 to 2011, no bladder-uterine fistulas were seen, but: 6 (13.95%) isolated
      uretero-vaginal fistulas and 6 (13.95%) uretero-vaginal fistulas associated with
      bladder-vaginal fistula, 31 (62%) bladder-vaginal fistulas of whom 20 (64.52%)
      bladder trigonal fistulas, 6 (19.34%) retro-trigonal fistulas and 2 (6.45%)
      urethral fistulas. Only three (9,68%) recto-vaginal fistulas were associated. The
      average fistula diameter was 2 cm. The fistulas were isolated in 40 cases (80%)
      and associated (VVF+uretero vaginal F) in 10 cases (20%). Thirty-five cases (70%)
      were primitive and 10 cases (20%) recurrent of whom 5 (10%) many recurrent.
      Fistulas were classified in simple fistula in 7 cases (14%) and complex fistula
      in 43 cases (86%) CONCLUSION: UGF remained relatively frequent in Cocody Teaching
      Hospital, but the lesions have favorably evolved in the last decade. Simple type
      of fistula became more frequent than complex ones. LEVEL OF EVIDENCE: 4.

PMID- 25864655
TI  - Regenerative treatments for orthopedic conditions.

PMID- 25864656
TI  - Cellular supplementation technologies for painful spine disorders.
AB  - Low back pain affects more than 80% of adults. A proportion of these adults
      develops chronic low back pain (CLBP) and becomes disabled by their condition.
      CLBP is expensive to diagnose and treat and in terms of associated loss of
      productivity in the work place setting by affected individuals. Although
      challenging, the source of CLBP can be identified. Contemporary literature
      contains several studies that have established prevalence estimates for various
      structural sources of CLBP. In young adults, the intervertebral disk is a common
      source of CLBP, once it incurs annular injury that heals incompletely. Effective
      treatment for painful disks currently is an unmet clinical need. In older adults,
      the facet and sacroiliac joints are more commonly responsible for CLBP. Although
      certain minimally invasive techniques do exist for these painful joints, an
      effective restorative intervention has yet to be established. Annular injury
      precipitates a physiologic response that can lead to a catabolic state within the
      disk that impairs disk restoration. Cell loss is a feature of this process as
      well as the pathophysiology associated with painful facet and sacroiliac joints.
      Cellular supplementation is an attractive treatment strategy to initiate the
      repair of an injured lumbosacral structure. The introduction of exogenous cells
      may lead to increased extracelluar matrix production and reduced pain and
      disability in diskogenic CLBP. Compelling data in animal studies have been
      produced, stimulating Food and Drug Administration-regulated trials in humans.
      Numerous questions remain regarding cell viability and sufficient native
      nutrients to support these cells. Clinical research protocols have focused
      predominantly on diskogenic CLBP, and very few have addressed painful facet
      and/or sacroiliac joints. 

PMID- 25864657
TI  - Stem cell therapies for treatment of cartilage and bone disorders:
      osteoarthritis, avascular necrosis, and non-union fractures.
AB  - The general ease of availability and strong fundamental science of autologous
      mesenchymal stem cells has prompted increasing application of such biologic
      therapies to address inherent orthopedic challenges of limited vascularity and
      ability to self-repair. This article provides a concise review of emerging
      mesenchymal stem cell applications for bone-related pathologies including
      cartilage, avascular necrosis, and fractures. 

PMID- 25864658
TI  - Where do injectable stem cell treatments apply in treatment of muscle, tendon,
      and ligament injuries?
AB  - Treatment options for muscle, tendon, and ligament injuries span a constantly
      evolving spectrum. For years, treatments focused on symptomatic relief. Closer
      scrutiny of symptomatic treatment suggests that the provision of transient relief
      of symptoms may have caused more harm than good. Cortisone injections provide a
      trade-off of short-term relief for poorer long-term outcomes. When conventional
      treatment failed, patients have faced limited options including surgery, which
      has increased risk and limited efficacy. Regenerative injections offer a more
      robust option for soft tissue disease. Basic science and clinical studies show
      conflicting results to support the use of platelet-rich plasma injections for
      soft tissue disorders, and even fewer trials have focused on injectable stem
      cells with limited findings. Additional studies are needed to determine the
      potential benefits of this regenerative therapy. 

PMID- 25864659
TI  - Safety and regulatory issues regarding stem cell therapies: one clinic's
      perspective.
AB  - Stem cells therapies have been in preclinical development for the past 2 decades.
      A rapidly evolving regulatory landscape has restrained many of these technologies
      from advancing from the bench to the bedside. Although the large-scale clinical
      safety of stem cell therapies remains to be fully tested, the total number of
      patients who have safely received these therapies is large and growing. Prima
      facie evidence would dictate that certain types of cell therapy are likely safer
      than others. Understanding the current regulation regarding stem cells involves a
      discussion of their safety profile, as the 2 issues are closely intertwined. 

PMID- 25864660
TI  - Regenerative treatments to enhance orthopedic surgical outcome.
AB  - In orthopedic surgery there has been a never-ending quest to improve surgical
      outcome and the patient's experience. Progression has been marked by the
      refinement of surgical techniques and instruments and later by enhanced
      diagnostic imaging capability, specifically magnetic resonance. Over time implant
      optimization was achieved, along with the development of innovative minimally
      invasive arthroscopic technical skills to leverage new versions of classic
      procedures and implants to improve short-term patient morbidity and initial, mid
      term, and long-term patient outcomes. The use of regenerative and/or biological
      adjuncts to aid the healing process has followed in the drive for continual
      improvement, and major breakthroughs in basic science have significantly
      unraveled the mechanisms of key healing and regenerative pathways. A wide
      spectrum of primary and complementary regenerative treatments is becoming
      increasingly available, including blood-derived preparations, growth factors,
      bone marrow preparations, and stem cells. This is a new era in the application of
      biologically active material, and it is transforming clinical practice by
      providing effective supportive treatments either at the time of the index
      procedure or during the postoperative period. Regenerative treatments are
      currently in active use to enhance many areas of orthopedic surgery in an attempt
      to improve success and outcome. In this review we provide a comprehensive
      overview of the peer-reviewed evidence-based literature, highlighting the
      clinical outcomes in humans both with preclinical data and human clinical trials
      involving regenerative preparations within the areas of rotator cuff, meniscus,
      ligament, and articular cartilage surgical repair. 

PMID- 25864661
TI  - A call for a standard classification system for future biologic research: the
      rationale for new PRP nomenclature.
AB  - Autologous cell therapies including platelet-rich plasma (PRP) and bone marrow
      concentrate (BMC) are increasingly popular options for soft tissue and joint
      related diseases. Despite increased clinical application, conflicting research
      has been published regarding the efficacy of PRP, and few clinical publications
      pertaining to BMC are available. Preparations of PRP (and BMC) can vary in many
      areas, including platelet concentration, number of white blood cells, presence or
      absence of red blood cells, and activation status of the preparation. The
      potential effect of PRP characteristics on PRP efficacy is often not well
      understood by the treating clinician, and PRP characteristics, as well as the
      volume of PRP delivered, are unfortunately not included in the methods of many
      published research articles. It is essential to establish a standard reporting
      system for PRP that facilitates communication and the interpretation and
      synthesis of scientific investigations. Herein, the authors propose a new PRP
      classification system reflecting important PRP characteristics based on
      contemporary literature and recommend adoption of minimal standards for PRP
      reporting in scientific investigations. Widespread adoption of these
      recommendations will facilitate interpretation and comparison of clinical studies
      and promote scientifically based progress in the field of regenerative medicine. 

PMID- 25864662
TI  - Advanced knee osteoarthritis in an active male: biologics or total knee
      replacement.

PMID- 25864663
TI  - The role of physiatry in regenerative medicine: the past, the present, and future
      challenges.
AB  - Historically, the foundation of physical medicine and rehabilitation training has
      provided the capabilities to optimize nonoperative treatments of a variety of
      musculoskeletal conditions, including acute and chronic muscle, tendon, ligament,
      and cartilage disorders. Such treatments include the use of nonsteroidal anti
      inflammatory drugs (NSAIDs), therapeutic modalities (eg, thermal and manual
      therapies), and corticosteroid injections in conjunction with specific
      rehabilitation exercises. Although NSAIDs, modalities, and corticosteroids may be
      helpful for short-term pain reduction and early recovery of function, they do not
      typically reverse the structural changes associated with degenerative conditions
      and may contribute to worse long-term outcomes by potentially interfering with
      tissue healing. Regenerative interventions, including platelet-rich plasma and
      mesenchymal stem cells, recently have been used to treat refractory painful
      conditions such as chronic tendinopathies because of the potential of these
      interventions to facilitate tissue healing. The future development of these
      regenerative techniques will require a variety of conditions to be met, including
      determining the most appropriate procedures based on the disease being treated;
      establishing the optimal preparations of these regenerative techniques; and
      providing clinicians, patients, and regulatory agencies with high-quality
      evidence demonstrating the safety, effectiveness, and long-term results of these
      treatments. Clarification of current regulatory uncertainty, improved access for
      all patients, proper training for clinicians who incorporate these techniques
      into their practice, and determination of the most appropriate postinjection
      protocols will allow physical medicine and rehabilitation specialists to play a
      unique role in the long-term management of patients with musculoskeletal and
      sports injuries. This article will also address the role physiatrists should have
      in the inevitable growth of regenerative medicine applications. 

PMID- 25864664
TI  - Technical issues in harvesting and concentrating stem cells (bone marrow and
      adipose).
AB  - The area of regenerative medicine, through the use of cell-based or biologic
      therapies, affords various options even with the choice of autologous stem cells
      and requires the clinician to use the currently evolving science along with the
      art of medicine. Potential sources for stem cells are embryos, fetuses, and
      adults (adipose tissue or adult cells, usually from skin [induced pluripotent],
      amniotic fluid, cartilage, bone marrow, menstrual blood, peripheral blood,
      placenta, skin, teeth, synovium, or umbilical cord blood). Issues regarding the
      source of stem cells include ethical and political/regulatory concerns, cell
      frequency, ease/difficulty of extraction, ease/difficulty of graft preparation,
      and host reaction to the implant. The most common sources of stem cells for
      orthopedic conditions are adipose tissue and bone marrow. Various opinions are
      expressed within the medical literature for and against both of these stem cell
      sources. This article will review patient concerns and preparation for obtaining
      cells; equipment, supplies, and staffing for the procedures; techniques, pearls,
      pitfalls, and risks of the procedures; and the manner of/options for processing
      the cells. 

PMID- 25864665
TI  - A plasmonic aptasensor for ultrasensitive detection of thrombin via arrested
      rolling circle amplification.
AB  - A sensitive signal generation mechanism for gold nanoparticle growth by reducing
      gold ions with hydrogen peroxide is applied in a plasmonic aptasensor, achieving
      naked-eye detection of thrombin at the single-molecule level based on the
      specific interaction of aptamer-thrombin via an arrested rolling circle
      amplification to yield horseradish peroxidase (HRP)-mimicking DNAzymes as
      biocatalysts. 

PMID- 25864666
TI  - "Molecular imaging for bioanalysis".

PMID- 25864667
TI  - New targets of molecular imaging in atherosclerosis: prehension of current
      status.
AB  - Atherosclerosis is an inflammatory disease in which immune mechanisms interact
      with diverse metabolic risk factors to initiate, propagate and activate lesions
      in the arterial wall. This process starts and evolves in response to cholesterol
      accumulation in arterial intima of the large and medium arteries. A number of
      modalities for inflammatory imaging in the arterial wall are currently in the
      stages of pre-clinical and clinical development. However, the identification of
      new targets that are linked to atherosclerosis to allow for dynamic ranges of
      diagnosis and prognosis still remains a challenge. In this review, we summarize
      the current status of atherosclerosis imaging aimed at macrophage-related, direct
      macrophage and non-macrophage as target molecules during different stages of
      atherogenesis. We also present activated macrophage, biofilm and amyloid fibrils
      as possible new targets for the development of non-invasive imaging probes to
      assess atherosclerosis. 

PMID- 25864668
TI  - Evaluation of enzymatic activities in living systems with small-molecular
      fluorescent substrate probes.
AB  - In this review, we aim to present an overview of how small-molecular fluorescent
      substrate probes for studying enzymatic functions are developed and how they are
      used in biological applications, under the following four headings: (1) History
      of Visual Detection of Enzymatic Activities, (2) Strategies to Design Fluorescent
      Substrate Probes to Measure Enzymatic Activities, (3) Development of Fluorescent
      Substrate Probes Suitable for Biological Studies, and (4) Biological Applications
      of Fluorescent Substrate Probes for Studying Enzymes. 

PMID- 25864669
TI  - Fluorescent protein-based biosensors to visualize signal transduction beneath the
      plasma membrane.
AB  - In response to extracellular stimuli, cells display a variety of behaviors,
      including proliferation, differentiation, morphological changes and migration.
      The analysis of the spatiotemporal regulation of signal transduction in living
      cells is needed for a better understanding of such behaviors, and such
      investigations have been greatly accelerated by the development of fluorescent
      protein-based biosensors. Currently, by using these biosensors a range of
      molecular actions, including lipid metabolism, protein activation, and ion
      dynamics, can be visualized in living cells. We recently reported that
      intracellular calcium, with its relevant downstream signaling pathways consisting
      of the small GTPase Ras and the lipid kinase phoshoinositide-3-kinase (PI3K), can
      be exploited in an efficient incorporation of influenza A viruses into host cells
      via endocytosis using a set of biosensors based on fluorescent proteins and the
      principle of Forster resonance energy transfer. Here, we focus this review on
      fluorescent protein-based biosensors that have been utilized in our recent
      research reports. 

PMID- 25864670
TI  - Sensing of intracellular environments by fluorescence lifetime imaging of
      exogenous fluorophores.
AB  - Fluorescence lifetime imaging (FLIM) has been recognized as a powerful microscopy
      technique to examine environments in living systems. The fluorescence lifetime
      does not depend on the photobleaching and optical conditions, which allows us to
      obtain quantitative information on intracellular environments by analyzing the
      fluorescence lifetime. A variety of exogenous fluorophores have been applied in
      FLIM measurements to examine cellular processes. Information on the correlation
      between the fluorescence lifetime and the physiological parameters is essential
      to elucidate the cellular environments from the fluorescence lifetime
      measurements of exogenous fluorophores. In this review, exogenous fluorophores
      used for lifetime-based sensing are summarized, with the expectation that it
      becomes a basis for selecting the fluorophore used to investigate the
      intracellular environment with FLIM. Experimental results of the intracellular
      sensing of pH, metal ions, oxygen, viscosity, and other physiological parameters
      on the basis of the FLIM measurements are described along with a brief
      explanation of the mechanism of the change in the fluorescence lifetime. 

PMID- 25864671
TI  - Chemical tools for probing histone deacetylase (HDAC) activity.
AB  - Histone deacetylases (HDACs) enzymes are responsible for removing epigenetic
      markers on histone proteins, which results in chromatin inactivation and gene
      repression. An evaluation of HDAC activity is essential for not only determining
      the physiological function of HDACs, but also for developing HDAC-targeting
      drugs. This review focuses on the chemical tools used to detect HDAC activity. We
      highlight activity-based probes and positron emission tomography probes based on
      the chemical structure of the inhibitors. We also summarize fluorogenic probes
      used in single-step methods for HDAC detection. These fluorogenic probes are
      designed based on the nucleophilicity of the amino group, aggregation via
      electrostatic interactions, and changes in the DNA binding properties. These
      fluorogenic systems may enable facile and rapid screening to evaluate HDAC
      inhibitors, which will contribute to the development of epigenetic drugs. 

PMID- 25864672
TI  - An efficient method is required to transfect non-dividing cells with genetically
      encoded optical probes for molecular imaging.
AB  - Genetically encoded fluorescent and bioluminescent reporters are now widely used
      for imaging and understanding of intracellular signaling in response to
      extracellular stimuli in real time in single living cells. Primary cultures are a
      valuable tool, and are often preferred over transformed or immortalized cell
      lines, since they are biologically more relevant and important in biomedical
      research and therapeutic development. To incorporate genetically encoded
      reporters into the primary culture of non-dividing cells, such as mouse or human
      pancreatic acinar cells, is not an easy task. This short review discusses the
      different methods available to transfect cell lines and primary cultures while
      especially focusing on pancreatic acinar cells with genetically encoded optical
      reporters to advance knowledge of the pathophysiology of pancreatitis. 

PMID- 25864673
TI  - Multimodal imaging of living cells with multiplex coherent anti-stokes raman
      scattering (CARS), third-order sum frequency generation (TSFG) and two-photon
      excitation fluorescence (TPEF) using a nanosecond white-light laser source.
AB  - The subnanosecond "white-light laser" source has been applied to multimodal,
      multiphoton, and multiplex spectroscopic imaging (M(3) spectroscopic imaging)
      with coherent anti-Stokes Raman scattering (CARS), third-order sum frequency
      generation (TSFG), and two-photon excitation fluorescence (TPEF). As the proof-of
      principle experiment, we performed simultaneous imaging of polystyrene beads with
      TSFG and TPEF. This technique is then applied to live cell imaging. Mouse L929
      fibroblastic cells are clearly visualized by CARS, TSFG, and TPEF processes. M(3)
      spectroscopic imaging provides various and unique cellular information with
      different image contrast based on each multiphoton process. 

PMID- 25864674
TI  - Multi-point scanning two-photon excitation microscopy by utilizing a high-peak
      power 1042-nm laser.
AB  - The temporal resolution of a two-photon excitation laser scanning microscopy
      (TPLSM) system is limited by the excitation laser beam's scanning speed. To
      improve the temporal resolution, the TPLSM system is equipped with a spinning
      disk confocal scanning unit. However, the insufficient energy of a conventional
      Ti:sapphire laser source restricts the field of view (FOV) for TPLSM images to a
      narrow region. Therefore, we introduced a high-peak-power Yb-based laser in order
      to enlarge the FOV. This system provided three-dimensional imaging of a
      sufficiently deep and wide region of fixed mouse brain slices, clear four
      dimensional imaging of actin dynamics in live mammalian cells and microtubule
      dynamics during mitosis and cytokinesis in live plant cells. 

PMID- 25864675
TI  - Fluorescence imaging of siRNA delivery by peptide nucleic acid-based probe.
AB  - We report on the use of a peptide nucleic acid (PNA)-based fluorescent probe for
      the analysis of siRNA delivery to living cells. The probe, Py-AA-TO, possesses
      thiazole orange (TO) and pyrene moieties in the C- and N-termini of PNA, and can
      function as a light-up probe capable of selective binding to 3'-overhanging
      nucleotides of target siRNAs. The affinity-labeling of the siRNAs with Py-AA-TO
      facilitates fluorescence imaging of cellular uptake of polymer-based carriers
      encapsulating the siRNAs (polyplexes) through endocytosis and subsequent
      sequestration into lysosome. In addition, flow cytometric measurements reveal
      that the monitoring of Py-AA-TO fluorescence inside the cells is successfully
      applicable to the analysis of the polyplex disassembly. These promising functions
      of Py-AA-TO are presented and discussed as a basis for the design of molecular
      probes for fluorescent imaging and quantitative analysis of the siRNA delivery
      process. 

PMID- 25864676
TI  - An enzyme-entrapped agarose gel for visualization of ischemia-induced L-glutamate
      fluxes in hippocampal slices in a flow system.
AB  - An agarose gel slip containing L-glutamate oxidase (GluOx), horseradish
      peroxidase (HRP) and a dye DA-64 is proposed as a tool for visualizing ischemia
      induced L-glutamate release in hippocampal slices in a flow system. The agarose
      slip with a detection limit of 6.0 +/- 0.8 MUmol L(-1) for L-glutamate enabled us
      to visualize L-glutamate fluxes in a flow system. The leak of a dye from the
      agarose gel was negligible and a diffusion blur due to spreading of Bindshedler's
      Green (BG) within the gel was suppressed. Monitoring the time-dependent change of
      ischemia-induced L-glutamate fluxes at neuronal regions CA1, DG and CA3 of
      hippocampal slices is demonstrated. 

PMID- 25864677
TI  - High-throughput live cell imaging and analysis for temporal reaction of G protein
      coupled receptor based on split luciferase fragment complementation.
AB  - For the design of therapeutic drugs, G protein coupled receptors (GPCRs) are
      notable targets. Many screening methods have been developed to identify effective
      agents for GPCR signaling. However, analyses of temporal variations of GPCR
      activity with specific ligands remain insufficient because of monitoring method
      limitations and difficulties. We previously developed a high-throughput
      bioluminescence measuring system to detect interactions of GPCR with beta
      arrestin based on split luciferase fragment complementation. By newly introducing
      a bioluminescence imaging technique into the system, we demonstrate a method for
      the temporal monitoring of GPCR-beta-arrestin interactions in living cells during
      stimulation by different ligands. 

PMID- 25864678
TI  - Phenylboronic acid-based (19)F MRI probe for the detection and imaging of
      hydrogen peroxide utilizing its large chemical-shift change.
AB  - Herein, we report on a new (19)F MRI probe for the detection and imaging of H2O2.
      Our designed 2-fluorophenylboronic acid-based (19)F probe promptly reacted with
      H2O2 to produce 2-fluorophenol via boronic acid oxidation. The accompanying (19)F
      chemical-shift change reached 31 ppm under our experimental conditions. Such a
      large chemical-shift change allowed for the imaging of H2O2 by (19)F chemical
      shift-selective MRI. 

PMID- 25864680
TI  - Spray-dried extract of Phyllanthus niruri L. reduces mucosal damage in rats with
      intestinal inflammation.
AB  - Phyllanthus niruri L. belongs to the Euphorbiaceae, and is known by the common
      name of 'stonebreaker' in Brazil. Some species within the Phyllanthus genus are
      widely used in traditional medicine to counteract different types of anti
      inflammatory diseases. OBJECTIVES: In this study, the preventive intestinal anti
      inflammatory activity of spray-dried extract of P. niruri (SDEPn) was tested in
      the model of acetic acid (10%)-induced ulcerative colitis in the rat. METHODS:
      Colitis animals were given orally at doses 25, 100 and 200 mg/kg. Colons tissue
      was analysed by macroscopic score, by histopathology score, by the
      immunohistochemical examination of tumour necrosis factor alpha, p53 and
      interferon gamma; by spectroscopic ultraviolet-visible spectrophotometry (UV/VIS)
      analysis of the levels of myeloperoxidase, malonaldehyde and total glutathione.
      KEY FINDINGS/RESULT: Pretreatment of the extract to colitic rats significantly
      attenuated colonic macroscopic damage induced by acetic acid (P < 0.01). Spray
      dried extract of P. niruri prevented glutathione depletion (P < 0.001) and
      malondialdehyde levels (P < 0.05) declined. Spray-dried extract of P. niruri
      significantly reduced microscopic damage to tissues, such as leukocyte
      infiltration accompanied by a significant reduction in myeloperoxidase activity
      (P < 0.5). Immunohistochemistry revealed a decline in the TNF-alpha, IFN-gamma
      and p53 protein (P < 0.05). CONCLUSION: Spray-dried extract of P. niruri has a
      beneficial effect in the acute phase of acetic acid-induced colitis in the rat,
      which is probably related to its antioxidant properties.

PMID- 25864681
TI  - A randomised clinical trial on the use of intermediate bonding on the retention
      of fissure sealants in children.
AB  - OBJECTIVE: To assess whether an adhesive bonding agent increases the retention of
      resin fissure sealants on first permanent molars (FPMs) and to determine any
      difference in sealant retention on occlusal, buccal, or palatal surfaces. The
      effect of the child's behaviour on the retention of the sealants was also
      assessed. METHODS: One hundred and twelve children were recruited (age range 5-15
      years). One operator placed sealants (Helioseal, Ivoclar Vivadent) on 390 FPMs
      using a split-mouth design. The study group, (n = 195), had an ethanol-based
      adhesive bond (ExciTEF, Ivoclar Vivadent) placed prior to sealant application,
      and no bond was used in the control group (n = 195). The sealants were reviewed
      after 12 months and analysed using Fisher's exact test. RESULTS: The addition of
      a bonding agent significantly increased sealant retention (P = 0.0005). Retention
      of bonded sealants on occlusal surfaces was higher (98%) than non-bonded sealants
      (93%) (P = 0.08). Bonded sealants placed on buccal/palatal surfaces were retained
      (92%) more successfully than non-bonded sealants (82%) (P = 0.0005). The
      behaviour of the patient significantly affected the retention of fissure sealants
      (P = 0.0001). CONCLUSIONS: The addition of an ethanol-based bonding agent
      significantly increased the retention of sealants at 12 months particularly on
      palatal fissures of maxillary first permanent molar teeth.

PMID- 25864683
TI  - Band energies of nanoparticle semiconductor electrodes determined by
      spectroelectrochemical measurements of free electrons.
AB  - Nanostructured semiconductor electrodes have garnered intense recent interest for
      use in various solar energy conversion systems since they offer the possibilities
      of circumventing low efficiencies associated with short diffusion length bulk
      materials as well as optimizing light absorption in dye-sensitized solar cells.
      In such context, knowledge of the conduction (ECB) and valence band (EVB) edge
      positions are the most important electronic properties in order to optimize
      performance and obtain a detailed understanding of relevant electron-transfer
      processes. However, there is no reliable direct method to measure the band edges
      in nanostructured semiconductor electrodes. Spectroeletrochemical methods have
      been utilized, but the nature of the absorbing species and interpretation of
      results are unsettled issues. Herein we describe a new simple
      spectroelectrochemical method which simultaneously produces the conduction band
      energy and the extinction coefficient, epsilon, of free conduction band electrons
      in nanoparticle TiO2 electrodes. 

PMID- 25864682
TI  - Comparison of cervical cancer screening results among 256,648 women in multiple
      clinical practices.
AB  - BACKGROUND: In the United States, human papillomavirus (HPV) and Papanicolaou
      (Pap) testing (cotesting) for cervical screening in women ages 30 to 65 years is
      the preferred strategy, and cytology alone is acceptable. Recently, a proprietary
      automated test for identifying high-risk HPV types for primary cervical screening
      was approved by the US Food and Drug Administration. The objective of the current
      study was to document extensive cervical screening among these screening options.
      METHODS: To investigate the sensitivity of various testing options for biopsy
      proven cervical intraepithelial neoplasia grade 3 or worse (>= CIN3) and cancer,
      the authors reviewed 256,648 deidentified results from women ages 30 to 65 years
      at the time of cotest who had a cervical biopsy specimen obtained within 1 year
      of the cotest. RESULTS: A positive cotest result was more sensitive (98.8%; 4040
      of 4090 cotests) for diagnosing >= CIN3 than either a positive HPV-only test
      (94%; 3845 of 4090 HPV-only tests) or a positive Pap-only test (91.3%; 3734 of
      4090 Pap-only tests; P < .0001). A positive Pap-only result was more specific
      (26.3%; 66,145 of 251,715 Pap-only tests) for diagnosing >= CIN3 than a positive
      HPV-only test (25.6%; 64,625 of 252,556 HPV-only tests) or a positive cotest
      (10.9%; 27,578 of 252,558 cotests; P < .0001). Of 526 cervical cancers, 98
      (18.6%) were HPV-only negative, 64 (12.2%) were Pap-only negative, and 29 (5.5%)
      were cotest negative. CONCLUSIONS: Compared with HPV-only testing, cotesting was
      more sensitive for the detection of >= CIN3 in women ages 30 to 65 years. The
      current data suggest that approximately 19% of women with cervical cancer may be
      misdiagnosed by an HPV-only cervical screen. It is important to consider these
      data as the guidelines for cervical cancer screening undergo revision. This is an
      open access article under the terms of the Creative Commons Attribution
      NonCommercial-NoDerivs License, which permits use and distribution in any medium,
      provided the original work is properly cited, the use is non-commercial and no
      modifications or adaptations are made.

PMID- 25864684
TI  - An important consideration in research and clinical practice.

PMID- 25864685
TI  - Oral implant placement and restoration by undergraduate students: clinical
      outcomes and student perceptions.
AB  - INTRODUCTION: Universities are developing and implementing implant dentistry
      training to prepare dental professionals for the growing treatment needs. This
      study describes how implant dentistry is taught at the KU Leuven and focuses on
      implant-related clinical outcomes. Perspectives of participating undergraduate
      students are analysed with a view to improve oral implant dentistry training.
      MATERIALS AND METHODS: Implant dentistry training at the KU Leuven consists of
      theoretical lectures, pre-clinical hands-on workshops and clinical
      (surgical/prosthetic) experience. Questionnaires were used to investigate the
      perceptions of students on the educational programme. Radiographs were taken at
      implant insertion, at healing abutment connection, at restoration/prosthesis
      insertion and after 1 and 2 years of functional loading. The marginal bone level
      was measured from the implant-abutment connection to the first visible bone-to
      implant contact. RESULTS: One hundred and twelve implants were placed by 56
      undergraduate students (61.5% of the total students) in 56 patients. After a
      follow-up time of 3 years, the cumulative implant survival rate, at implant
      level, was 97.1%. The mean marginal bone loss after 1 and 2 years in function was
      0.35 mm and 0.39 mm, respectively. Eighty percentage of students were satisfied
      with the training, and they considered this sufficient preparation to perform
      implant placement under close supervision. CONCLUSIONS: The clinical outcome of
      implant treatment performed by undergraduate students under close supervision is
      similar to that reported by experienced clinicians/research teams. Clinical,
      surgical as well as restorative experience in addition to theoretical and pre
      clinical training seems beneficial when implementing implant dentistry in the
      undergraduate programmes.

PMID- 25864686
TI  - Ruthenium-oxide-coated sodium vanadium fluorophosphate nanowires as high-power
      cathode materials for sodium-ion batteries.
AB  - Sodium-ion batteries are a very promising alternative to lithium-ion batteries
      because of their reliance on an abundant supply of sodium salts, environmental
      benignity, and low cost. However, the low rate capability and poor long-term
      stability still hinder their practical application. A cathode material, formed of
      RuO2 -coated Na3 V2 O2 (PO4 )2 F nanowires, has a 50 nm diameter with the space
      group of I4/mmm. When used as a cathode material for Na-ion batteries, a
      reversible capacity of 120 mAh g(-1) at 1 C and 95 mAh g(-1) at 20 C can be
      achieved after 1000 charge-discharge cycles. The ultrahigh rate capability and
      enhanced cycling stability are comparable with high performance lithium cathodes.
      Combining first principles computational investigation with experimental
      observations, the excellent performance can be attributed to the uniform and
      highly conductive RuO2 coating and the preferred growth of the (002) plane in the
      Na3 V2 O2 (PO4 )2 F nanowires.

PMID- 25864687
TI  - Open adoption: a review of the literature with recommendations to adoption
      practitioners.
AB  - As openness in adoption is still in its infancy, there has not been much
      systematic research on open adoption. This practice involves anything from
      sharing non-identifying information through an intermediary to regular face-to
      face fully identifying information-sharing and contact between all members of the
      adoption triangle - the birthparent/s, the adoptive parents and the adoptees.
      Open adoption appears to offer birthparent/s the greatest benefits. Although
      adoptive parents express varying degrees of positive reactions to being involved
      in open adoptions, there are instances of discomfort and reservations expressed
      by some. With no studies investigating adoptees' own perceptions around contact
      with their birthparent/s, the potential risks and/or benefits of open adoption
      for the children involved, is inferred from adoptive parents' reports and
      theoretical perspectives. Adoption practitioners advocating openness in adoption,
      should be prepared for additional investments in time, effort and emotional
      energy in order to facilitate what is not a discrete event in time, but an on
      going process. 

PMID- 25864688
TI  - Social contexts, age and juvenile delinquency: a community perspective.
AB  - Objective - Social disorganisation of communities, family bonds, school bonds,
      the peer group and age, have been shown to be related (either positively or
      negatively) to delinquency. This study addressed gaps in the literature by (1)
      using a large and randomly drawn sample of adolescents, within a large number of
      randomly selected communities; (2) investigating the influence of community
      social disorganisation directly on delinquency, while including in the same model
      the moderating effect of community social disorganisation on the micro-contexts
      of family, school, and peer group, as well as the direct effects of these micro
      contexts; and (3) including age as a variable likely to have both direct effects
      on delinquency and moderating effects on the micro- and macro-level social
      contexts. Method - The public-use data set of Wave I of the (US) National
      Longitudinal Study of Adolescent Health was used. The model was tested using
      hierarchical linear modelling and included the social disorganisation of
      communities; adolescents' bonds to school and family, family controls and
      involvement with a deviant peer group; and age and its interaction with these
      social contexts. Results - Community social disorganisation was found to be
      positively related to delinquency, but effects of micro-level contexts were not
      found to be moderated by social disorganisation. Family bonds and controls, and
      school bonds, were negatively related to delinquency. No effect of peer group was
      found. Age was found to have a direct effect; effects of the interaction of age
      with family controls and age with school bonds were also significant. Conclusions
      - Results strengthen those from previous studies (using more limited samples)
      which show that integrated views of macro- and micro-level social contexts and
      developmental trends are necessary to understand delinquency. 

PMID- 25864689
TI  - Prevalence and attitudinal predictors of child sexual offending in a nonforensic
      sample of South African high school males.
AB  - Objective - The prevalence, and attitudinal predictors, of sexual aggression were
      examined in a non-forensic sample of South African high school males. Method -
      Survey questionnaires were administered to 446 males (aged 16 to 25 years)
      attending schools in the greater Durban area, South Africa. Results - A history
      of sexually aggressive behaviour was reported by 66.8% of respondents, with 17.5%
      reporting an act of sexual aggression that met the legal definition of rape or
      attempted rape. A multivariate analysis of variance indicated a significant
      relationship between sexually abusive behaviour and attitudes supportive of both
      sexual and physical aggression. Additionally, a tendency to attribute blame to
      the victim of sexual aggression and attitudes reflecting an internalised culture
      of violence significantly discriminated between respondents who committed
      rape/attempted rape, indecent assault, and crimen injuria. Conclusions - These
      findings indicate relatively high rates of sexual offending among South African
      high school males and suggest that primary prevention programmes are likely to be
      most effective if they target attitudes supportive of both sexual and physical
      violence. 

PMID- 25864690
TI  - The usefulness of commercially available 'culture fair' tests in the assessment
      of educational success in Grade 1 Black pupils in South Africa - an explorative
      study.
AB  - School failure among Grade 1 pupils and the subsequent drop out rate is of major
      concern in South Africa, especially as far as Black pupils are concerned. The
      school drop out rate is estimated to be four times higher in Black pupils than
      White children. The dilemma for the professionals in assessing children, who are
      experiencing difficulty at school, and who are from disadvantaged, non-English
      speaking communities, is the paucity of reliable, objective tests to identify
      children at risk. The purpose of this study was to determine whether commercially
      available 'culture fair' tests could be used to evaluate Black pupils early in
      Grade 1 and if they were associated with educational success. A parental
      questionnaire was used to examine non-academic predictors of educational success,
      such as birth history, socio-economic status and the medical profile. One hundred
      and three Grade 1 pupils were tested in the first term. The tests used were the
      Griffiths Mental Developmental Scales, WISC mazes, Raven's Progressive Matrices,
      Developmental Test of Visual Motor Integration (VMI), Motor-free Visual
      Perceptual Test (MVPT), Test of Visual Perceptual Skills (TVPS) and the Draw-a
      Person Test (DAP). Several backward elimination stepwise regression analysis
      procedures were used to examine the multivariate associations between the
      psychometric and nonacademic variables and three outcome variables, namely the
      mid and end of year aggregates and a pass/fail dichotomous variable. Non-academic
      variables that were significantly associated with academic success were asphyxia,
      overcrowding and maternal education. The psychometric subtests that were
      significantly associated with academic achievement were the VMI, DAP, the Raven's
      Progressive Matrices, TVPS and WISC mazes. Commercially available 'culture fair'
      tests are significantly associated with educational success in Black Grade 1
      pupils where standardised, comprehensive tests are not available. To evaluate to
      what extent these tests would be reliable predictors of educational success
      further studies would have to analyse a larger cohort of pupils. 

PMID- 25864691
TI  - Health actions and health promotion among a sample of rural Black South African
      children.
AB  - The purpose of this study was to investigate the daily activities that young
      South African children perceived as health related activities. The sample
      included 117 children (33, ages 5-7 years; 44, ages 8-10 years; and 40, ages 11
      12 years) chosen by two-stage cluster sampling in a rural community of the
      central region of the Northern Province. Results indicated that the most
      important health actions around healthy eating were, 'washing hands'; around
      dressing, 'wearing warm clothes'; around keeping clean, 'washing body and hair';
      going to sleep, 'washing body'; activity at school, 'read and write'; recess and
      leisure time, 'playing football or netball'. Personal hygiene (washing, brushing
      teeth, etc.) was the most common health action of the children around healthy
      eating, keeping clean and going to sleep. Some health actions were insufficiently
      mentioned, brushing teeth for example and some wrongly mentioned such as eating
      porridge before going to sleep. This study showed that children have insufficient
      knowledge and understanding about health related activities. Results suggest that
      health professionals and teachers should consider providing more information
      about health related activities for young children. 

PMID- 25864692
TI  - Culture and infancy: a critical examination.
AB  - Over 90% of infants born in the world live in low-income countries, but most
      scholarly knowledge about infancy is produced in wealthy countries. More
      knowledge is consequently needed about infancy throughout the world. There are
      logistical and cultural difficulties associated with gaining this information,
      but in this paper I focus on the broader ideological context of knowledge
      production about infancy world-wide. Using a recently published volume, A World
      of Babies: Imagined Childcare Guides for Seven Societies (DeLoache and Gottlieb
      2000) as an exemplar, I will show that the representation of infancy as an
      ideology-free or even romanticised zone may do little to forward our
      understanding of infancy and culture. 

PMID- 25864693
TI  - Treatment for perinatal disturbance.
AB  - The perinatal period of transition to parenthood is one of heightened passions,
      which revive the expectant and new parents' own early experiences, and
      particularly unresolved emotional issues. For many deprived parents close contact
      with an infant reactivates old grievances at this time of vulnerability, which
      may manifest in syndromes of self-pity or in fury and vengefulness over past
      humiliations. Unprocessed dissatisfactions tend to erupt in disruptive or
      repetitious behaviours, which inevitably affect the baby in their care. In
      addition, childbearing in societies undergoing transition, like South Africa, may
      be fraught with extra stresses. These include socio-economic disadvantages and
      social adversity arising from geographical relocation and breakdown of
      traditional patterns, and psychological distress due to past or current
      experiences of physical or emotional trauma and neglect and relationship
      difficulties which tend to be exacerbated in times of rapid cultural change in
      the absence of a wider supportive network. It is argued that, in societies with
      scarce resources, the mental health focus must be on prevention, detection of
      high-risk groups and early intervention. Two tables are presented - of risk
      indicators and treatment guidelines, which may be applied during the perinatal
      period to minimise postnatal disturbance. Health workers with minimal training
      can be effective in screening and in some cases, delivering prophylactic or
      postnatal care to people at potential risk. Offering such help may enable
      resilient people in a state of crisis or transition to marshal their own
      resources. For others longer-term professional help may be required to shift the
      chronic effects of cumulative trauma by reworking emotional predicaments in a
      caring and safe environment. 

PMID- 25864694
TI  - Counselling and coping.

PMID- 25864695
TI  - Steering by the stars: being young in South Africa.

PMID- 25864696
TI  - Introducing the journal of child and adolescent mental health.

PMID- 25864697
TI  - The South African Association for Child and Adolescent Psychiatry and Allied
      Professions (SAACAPAP).

PMID- 25864698
TI  - Anticancer Drugs in End-Stage Kidney Disease Patients.
AB  - The increased incidence of malignancies in patients with chronic kidney patients
      and especially in end-stage kidney disease (ESKD) patients has been discussed
      since the mid-1970s. Consequently, oncologists, nephrologists, and pharmacists
      are increasingly facing challenging situations of cytotoxic drug handling in
      dialysis patients because of pharmacokinetic modifications. In these patients,
      two main issues must be considered. First, the absence of renal function in
      hemodialysis (HD) patients may necessitate drug dosage reduction. Therefore, drug
      prescription must be cautiously checked before administration with appropriate
      dosage adjustment whenever necessary to ensure efficacy while avoiding overdosage
      and related side effects. Second, drug clearance by dialysis session must be
      taken into account for appropriate chemotherapy timing administration to avoid
      drug removal, which may result in a loss of efficacy. These two main
      considerations must not be considered as a contra-indication to chemotherapy in
      ESKD patients, but more as a need for an individualized prescription according to
      available recommendations. 

PMID- 25864700
TI  - Immunohistochemistry for CD117 (KIT) is effective in distinguishing cutaneous
      adnexal tumors with apocrine/eccrine or sebaceous differentiation from other
      epithelial tumors of the skin.
AB  - BACKGROUND: The aim of this study was to evaluate the effectiveness of CD117
      immunostaining for diagnosing cutaneous adnexal tumors, which has not been
      previously established. METHODS: CD117 immunostaining was performed on
      representative sections of 87 clinicopathologically confirmed cutaneous
      apocrine/eccrine tumors, 13 sebaceous tumors, 52 follicular tumors, 55
      keratinocytic tumors, 24 metastatic tumors of the skin of known origin and 1
      mammary Paget disease. Staining of 5-50% of cells was considered focally
      positive, and staining of 51-100% of cells was considered diffusely positive.
      Staining intensity was semi-quantitatively graded as weak, moderate or strong.
      RESULTS: A total of 82 (94.3%) tumors with apocrine/eccrine differentiation were
      CD117-positive, whereas one mucinous carcinoma, one apocrine carcinoma, and three
      primary cutaneous extramammary Paget diseases were CD117-negative. For most
      positive cases, staining was diffuse (64/82 cases) and moderate to strong in
      intensity (74/82). Twelve (92.3%) sebaceous tumors were CD117-positive, showing
      mainly focal (9/12) and weak (7/12) positivity. Of the 52 follicular tumors, all
      4 cases of pilomatricoma and other 5 tumors were positive for CD117. Of the 55
      keratinocytic tumors, only 2 cases were CD117-positive. The 24 metastatic tumors
      and mammary Paget disease were CD117-negative. CONCLUSIONS: CD117 may be useful
      for the differential diagnosis of cutaneous adnexal tumors.

PMID- 25864699
TI  - Changes in glucose metabolism in people with different glucose metabolism
      disorders at baseline: follow-up results of a Finnish national diabetes
      prevention programme.
AB  - AIM: To examine changes in glucose metabolism (fasting and 2-h glucose) during
      follow-up in people with impaired fasting glucose in comparison with changes in
      people with isolated impaired glucose tolerance, people with impaired fasting
      glucose and impaired glucose tolerance combined and people with screening
      detected Type 2 diabetes at baseline, among those who participated in a diabetes
      prevention programme conducted in Finland. METHODS: A total of 10 149 people at
      high risk of Type 2 diabetes took part in baseline examination. Of 5351
      individuals with follow-up >= 9 months, 1727 had impaired glucose metabolism at
      baseline and completed at least one lifestyle intervention visit. Most of them
      (94.6%) were overweight/ obese. RESULTS: Fasting glucose decreased during follow
      up among overweight/obese people in the combined impaired fasting glucose and
      impaired glucose tolerance group (P = 0.044), as did 2-h glucose in people in the
      isolated impaired glucose tolerance group (P = 0.0014) after adjustment for age,
      sex, medication and weight at baseline, follow-up time and changes in weight,
      physical activity and diet. When comparing changes in glucose metabolism among
      people with different degrees of glucose metabolism impairment, fasting glucose
      concentration was found to have increased in those with isolated impaired glucose
      tolerance (0.12 mmol/l, 95% Cl 0.05 to 0.19) and it decreased to a greater extent
      in those with screening-detected Type 2 diabetes (-0.54 mmol/l, 95% Cl -0.69 to 
      0.39) compared with those with impaired fasting glucose (-0.21 mmol/l, 95% Cl 
      0.27 to -0.15). Furthermore, 2-h glucose concentration decreased in the isolated
      impaired glucose tolerance group (-0.82 mmol/l, 95% Cl -1.04 to -0.60), in the
      combined impaired fasting glucose and impaired glucose tolerance group (-0.82
      mmol/l, 95% Cl -1.07 to -0.58) and in the screening-detected Type 2 diabetes
      group (-1.52, 95% Cl -1.96 to -1.08) compared with those in the impaired fasting
      glucose group (0.26 mmol/l, 95% Cl 0.10 to 0.43). Results were statistically
      significant even after adjustment for covariates (P < 0.001 in all models).
      CONCLUSIONS: Changes in glucose metabolism differ in people with impaired fasting
      glucose from those in people with isolated impaired glucose tolerance, people
      with impaired fasting glucose and impaired glucose tolerance combined and people
      with screening-detected Type 2 diabetes.

PMID- 25864701
TI  - Capillary malformations: a classification using specific names for specific skin
      disorders.
AB  - The name capillary malformation has caused much confusion because it is presently
      used to designate numerous quite different disorders such as naevus flammeus, the
      salmon patch, the vascular naevus of the hereditary 'megalencephaly-capillary
      malformation syndrome' and the skin lesions of non-hereditary traits such as
      'capillary malformation-arteriovenous malformation' and 'microcephaly-capillary
      malformation'. To avoid such bewilderment, the present review describes the
      distinguishing clinical and genetic criteria of 20 different capillary
      malformations, and a specific name is given to all of them. The group of
      capillary naevi includes naevus flammeus, port-wine naevus of the Proteus type,
      port-wine naevus of the CLOVES type, naevus roseus, rhodoid naevus, cutis
      marmorata telangiectatica congenita, congenital livedo reticularis, segmental
      angioma serpiginosum, naevus anaemicus, naevus vascularis mixtus and
      angiokeratoma circumscriptum. Capillary lesions that perhaps represent naevi are
      the mesotropic port-wine patch, Carter-Mirzaa macules, unilateral punctate
      telangiectasia and unilateral naevoid telangiectasia of the patchy type.
      Capillary malformations that do not represent naevi include X-linked
      angiokeratoma corporis diffusum (Fabry disease), autosomal dominant angiokeratoma
      corporis diffusum, hereditary haemorrhagic telangiectasia, hereditary angioma
      serpiginosusm and the salmon patch. In this way, we are able to discriminate
      between various non-hereditary capillary naevi such as naevus roseus and the
      hereditary rhodoid naevus and several hereditary traits that do not represent
      naevi such as angiokeratoma corporis diffusum and hereditary haemorrhagic
      telangiectasia; between four different types of port-wine stains, three of them
      being lateralized and one being mesotropic; between cutis marmorata
      telangiectatica congenita and congenital livedo reticularis; between
      telangiectatic naevi and the vasoconstrictive naevus anaemicus; and between two
      different types of angiokeratoma corporis diffusum. Finally, arguments are
      presented why the salmon patch ('stork bite', 'naevus simplex') cannot be
      categorized as a naevus. 

PMID- 25864702
TI  - Recording the dynamic endocytosis of single gold nanoparticles by AFM-based force
      tracing.
AB  - We utilized force tracing to directly record the endocytosis of single gold
      nanoparticles (Au NPs) with different sizes, revealing the size-dependent
      endocytosis dynamics and the crucial role of membrane cholesterol. The force,
      duration and velocity of Au NP invagination are accurately determined at the
      single-particle and microsecond level unprecedentedly. 

PMID- 25864703
TI  - Serum infliximab concentrations and disease activity: a descriptive study of
      patients with psoriasis.

PMID- 25864704
TI  - Tailoring recombinant protein quality by rational media design.
AB  - Clinical efficacy and safety of recombinant proteins are closely associated with
      their structural characteristics. The major quality attributes comprise
      glycosylation, charge variants (oxidation, deamidation, and C- & N-terminal
      modifications), aggregates, low-molecular-weight species (LMW), and
      misincorporation of amino acids in the protein backbone. Cell culture media
      design has a great potential to modulate these quality attributes due to the
      vital role of medium in mammalian cell culture. The purpose of this review is to
      provide an overview of the way both classical cell culture medium components and
      novel supplements affect the quality attributes of recombinant therapeutic
      proteins expressed in mammalian hosts, allowing rational and high-throughput
      optimization of mammalian cell culture media. A selection of specific and/or
      potent inhibitors and activators of oligosaccharide processing as well as
      components affecting multiple quality attributes are presented. Extensive
      research efforts in this field show the feasibility of quality engineering
      through media design, allowing to significantly modulate the protein function.

PMID- 25864705
TI  - Cue Consistency Associated with Physical Activity Automaticity and Behavior.
AB  - Physical activity is partly regulated by automatic processes such as habits (ie,
      well-learned responses to cues), but it remains unclear what cues trigger these
      processes. This study examined the relations of physical activity automaticity
      and behavior with the consistency of people, activity, routine, location, time,
      and mood cues present upon initiation of physical activity behavior. Australian
      adults (N = 1,244, 627 female, M age = 55 years) reported their physical activity
      automaticity, behavior, and the degree of consistency of these cues each time
      they start a physical activity behavior. Multiple regression models, which
      accounted for gender and age, revealed that more consistent routine and mood cues
      were linked to more physical activity automaticity; whereas more consistent time
      and people cues were linked to more physical activity behavior. Interventions may
      more effectively translate into long-lasting physical activity habits if they
      draw people's attention to the salient cues of time, people, routine, and mood.

PMID- 25864706
TI  - Anti-inflammatory potential of a lipid-based formulation of a rotenoid-rich
      fraction prepared from Boerhavia diffusa.
AB  - CONTEXT: Boerhavia diffusa L. (Nyctaginaceae) roots are used in Ayurveda for
      treating inflammatory diseases. Generally poor oral bioavailability is a major
      problem associated with herbal drugs. OBJECTIVE: To develop a phospholipid
      complex of rotenoid-rich fraction (RRF) and evaluate its in vivo anti
      inflammatory activity and pharmacokinetic study. MATERIALS AND METHODS: RRF was
      prepared from a 70% ethanol extract of B. diffusa roots. This RRF was complexed
      with phosphatidylcholine by refluxing in 70% ethanol. In vivo anti-inflammatory
      activity of RRF-PC and RRF was determined using the carrageenan-induced rat paw
      edema method, at a dose equivalent to 100 mg/kg p.o. of RRF. Edema volume was
      calculated at 3 and 5 h. The plasma concentration of boeravinone B was estimated
      in rats at a same dose level. Blood samples were collected at 1, 2, 4, 6, 8, 10,
      12, 24, and 36 h. RESULTS: (1)H and (31)P NMR spectra of RRF-PC showed up-field
      shift of protons of the (+)N(CH3)3 group (3.37 -> 3.23) and the phosphorus atom (
      1.26 -> -1.57 ppm), respectively, which confirmed phospholipid complex formation
      between phosphatidylcholine [PO4 and (+)N(CH3)3 groups] and phytoconstituents by
      hydrogen bonding. The RRF-PC showed significantly enhanced in vivo anti
      inflammatory activity (64%) as compared with RRF (48%) and ibuprofen (50%) at 5 h
      (p < 0.001). Furthermore, detected plasma concentration of boeravinone B was two
      times higher in RRF-PC (75 ng/mL) as compared with RRF (40 ng/mL). CONCLUSION:
      The present study demonstrated an increased anti-inflammatory potential and
      higher plasma level of boeravinone B in lipid-based formulation (RRF-PC) as
      compared with RRF.

PMID- 25864707
TI  - Incorporation of ionic liquid into porous polymer monoliths to enhance the
      separation of small molecules in reversed-phase high-performance liquid
      chromatography.
AB  - An ionic liquid was incorporated into the porous polymer monoliths to afford
      stationary phases with enhanced chromatographic performance for small molecules
      in reversed-phase high-performance liquid chromatography. The effect of the ionic
      liquid in the polymerization mixture on the performance of the monoliths was
      studied in detail. While monoliths without ionic liquid exhibited poor resolution
      and low efficiency, the addition of ionic liquid to the polymerization mixture
      provides highly increased resolution and high efficiency. The chromatographic
      performances of the monoliths were demonstrated by the separations of various
      small molecules including aromatic hydrocarbons, isomers, and homologues using a
      binary polar mobile phase. The present column efficiency reached 27 000 plates/m,
      which showed that the ionic liquid monoliths are alternative stationary phases in
      the separation of small molecules by high-performance liquid chromatography. 

PMID- 25864708
TI  - Celiac disease 2015 update: new therapies.
AB  - Celiac disease (CD) is a chronic, small intestinal, immune-mediated enteropathy
      triggered by exposure to dietary gluten in genetically susceptible individuals.
      Currently, lifelong adherence to a gluten-free diet (GFD) is the only available
      treatment. However, GFD alone is not sufficient to relieve symptoms, control
      small intestinal inflammation and prevent long-term complications in many
      patients. The GFD has its challenges including issues related to adherence,
      lifestyle restrictions and cost. As a result, there is growing interest in and a
      need for non-dietary therapies to manage this condition. In recent years,
      different targets in the immune-mediated cascade of CD have been identified in
      clinical and pre-clinical trials for potential therapies. This review will
      discuss the latest non-dietary therapies in CD, including endopeptidases,
      modulators of enterocyte tight junctions and agents involved in gluten
      tolerization and immunomodulation. We will also discuss the potential
      implications of approved therapeutics on CD clinical practice. 

PMID- 25864709
TI  - Pan-cancer transcriptome analysis reveals long noncoding RNAs with conserved
      function.
AB  - A growing number of gene-centric studies have highlighted the emerging
      significance of lncRNAs in cancer. However, these studies primarily focus on a
      single cancer type. Therefore, we conducted a pan-cancer analysis of lncRNAs
      comparing tumor and matched normal expression levels using RNA-Seq data from ~
      3,000 patients in 8 solid tumor types. While the majority of differentially
      expressed lncRNAs display tissue-specific expression we discovered 229 lncRNAs
      with outlier or differential expression across multiple cancers, which we refer
      to as 'onco-lncRNAs'. Due to their consistent altered expression, we hypothesize
      that these onco-lncRNAs may have conserved oncogenic and tumor suppressive
      functions across cancers. To address this, we associated the onco-lncRNAs in
      biological processes based on their co-expressed protein coding genes. To
      validate our predictions, we experimentally confirmed cell growth dependence of 2
      novel oncogenic lncRNAs, onco-lncRNA-3 and onco-lncRNA-12, and a previously
      identified lncRNA CCAT1. Overall, we discovered lncRNAs that may have broad
      oncogenic and tumor suppressor roles that could significantly advance our
      understanding of cancer lncRNA biology.

PMID- 25864711
TI  - Synthesis of an [(NHC)2 Pd(SiMe3 )2 ] Complex and Catalytic cis-Bis(silyl)ations
      of Alkynes with Unactivated Disilanes.
AB  - The novel complex cis-[(ITMe)2 Pd(SiMe3 )2 (ITMe=1,3,4,5-tetramethylimidazol-2
      ylidene) has been synthesized by mild oxidative cleavage of Me3 SiSiMe3 using
      [(ITMe)2 Pd(0) ]. The use of this complex as precatalyst for the cis
      bis(silyl)ation of alkynes using unactivated disilanes is reported. 

PMID- 25864710
TI  - A valuable and promising method for recording brain activity in behaving newborn
      rodents.
AB  - Neurophysiological recording of brain activity has been critically important to
      the field of neuroscience, but has contributed little to the field of
      developmental psychobiology. The reasons for this can be traced largely to
      methodological difficulties associated with recording neural activity in behaving
      newborn rats and mice. Over the last decade, however, the evolution of methods
      for recording from head-fixed newborns has heralded a new era in developmental
      neurophysiology. Here, we review these recent developments and provide a step-by
      step primer for those interested in applying the head-fix method to their own
      research questions. Until now, this method has been used primarily to investigate
      spontaneous brain activity across sleep and wakefulness, the contributions of the
      sensory periphery to brain activity, or intrinsic network activity. Now, with
      some ingenuity, the uses of the head-fix method can be expanded to other domains
      to benefit our understanding of brain-behavior relations under normal and
      pathophysiological conditions across early development.

PMID- 25864713
TI  - Multiscale tomographic analysis of heterogeneous cast Al-Si-X alloys.
AB  - The three-dimensional microstructure of cast AlSi12Ni and AlSi10Cu5Ni2 alloys is
      investigated by laboratory X-ray computed tomography, synchrotron X-ray computed
      microtomography, light optical tomography and synchrotron X-ray computed
      microtomography with submicrometre resolution. The results obtained with each
      technique are correlated with the size of the scanned volumes and resolved
      microstructural features. Laboratory X-ray computed tomography is sufficient to
      resolve highly absorbing aluminides but eutectic and primary Si remain
      unrevealed. Synchrotron X-ray computed microtomography at ID15/ESRF gives better
      spatial resolution and reveals primary Si in addition to aluminides. Synchrotron
      X-ray computed microtomography at ID19/ESRF reveals all the phases >= ~1 MUm in
      volumes about 80 times smaller than laboratory X-ray computed tomography. The
      volumes investigated by light optical tomography and submicrometre synchrotron X
      ray computed microtomography are much smaller than laboratory X-ray computed
      tomography but both techniques provide local chemical information on the types of
      aluminides. The complementary techniques applied enable a full three-dimensional
      characterization of the microstructure of the alloys at length scales ranging
      over six orders of magnitude. 

PMID- 25864712
TI  - Incidence and natural history of challenge-proven cow's milk allergy in European
      children--EuroPrevall birth cohort.
AB  - BACKGROUND: Cow's milk allergy (CMA) is one of the most commonly reported
      childhood food problems. Community-based incidence and prevalence estimates vary
      widely, due to possible misinterpretations of presumed reactions to milk and
      differences in study design, particularly diagnostic criteria. METHODS: Children
      from the EuroPrevall birth cohort in 9 European countries with symptoms possibly
      related to CMA were invited for clinical evaluation including cows' milk-specific
      IgE antibodies (IgE), skin prick test (SPT) reactivity and double-blind, placebo
      controlled food challenge. RESULTS: Across Europe, 12 049 children were enrolled,
      and 9336 (77.5%) were followed up to 2 years of age. CMA was suspected in 358
      children and confirmed in 55 resulting in an overall incidence of challenge
      proven CMA of 0.54% (95% CI 0.41-0.70). National incidences ranged from 1% (in
      the Netherlands and UK) to <0.3% (in Lithuania, Germany and Greece). Of all
      children with CMA, 23.6% had no cow's milk-specific IgE in serum, especially
      those from UK, the Netherlands, Poland and Italy. Of children with CMA who were
      re-evaluated one year after diagnosis, 69% (22/32) tolerated cow's milk,
      including all children with non-IgE-associated CMA and 57% of those children with
      IgE-associated CMA. CONCLUSIONS: This unique pan-European birth cohort study
      using the gold standard diagnostic procedure for food allergies confirmed
      challenge-proven CMA in <1% of children up to age 2. Affected infants without
      detectable specific antibodies to cow's milk were very likely to tolerate cow's
      milk one year after diagnosis, whereas only half of those with specific
      antibodies in serum 'outgrew' their disease so soon.

PMID- 25864714
TI  - Correlating RANK ligand/RANK binding kinetics with osteoclast formation and
      function.
AB  - The interaction between Receptor Activator of NF-kappaB Ligand (RANKL) and its
      receptor RANK is essential for the differentiation and bone resorbing capacity of
      the osteoclast. Osteoprotegerin (OPG), a soluble homodimer, acts as a decoy
      receptor for RANKL and thus inhibits osteoclastogenesis. An imbalance in the
      RANKL/RANK/OPG axis, with decreased OPG and/or increased RANKL, is associated
      with diseases that favor bone loss, including osteoporosis. Recently, we
      established a yeast surface display system and screened libraries of randomly
      mutated RANKL proteins to identify mutations that abolish binding to OPG while
      preserving recognition of RANK. These efforts yielded several RANKL variants
      possessing substantially higher affinity for RANK compared to their wild-type
      (WT) counterpart. Using recombinant RANKL mutant proteins, we find those with
      increased affinity for RANK produce more robust signaling in osteoclast lineage
      cells and have greater osteoclastogenic potential. Our results are the first to
      document gain of function RANKL mutations. They indicate that the physiological
      RANKL/RANK interaction is not optimized for maximal signaling and function,
      perhaps reflecting the need to maintain receptor specificity within the tumor
      necrosis factor superfamily (TNFSF). Instead, we find, a biphasic relationship
      exists between RANKL/RANK affinity and osteoclastogenic capacity. In our panel of
      RANKL variants, this relationship is driven entirely by manipulation of the
      kinetic off-rate. Our structure-based and yeast surface display-derived insights
      into manipulating this critical signaling axis may aid in the design of novel
      anti-resorptive therapies as well as provide a paradigm for design of other
      receptor-specific TNF superfamily ligand variants.

PMID- 25864715
TI  - Production of squalene by lactose-fermenting yeast Kluyveromyces lactis with
      reduced squalene epoxidase activity.
AB  - Utilization of yeast as squalene source for commercial use is limited by
      relatively high production costs. The ability of Kluyveromyces lactis to grow on
      cheap lactose-containing diary industry wastes could improve the economy of the
      production process. We therefore tested the potential of this yeast for squalene
      production. Accumulation of squalene was induced by partial inhibition of
      squalene epoxidase by a specific inhibitor terbinafine. Kluyveromyces lactis
      cultivated on glucose and lactose media showed similar growth sensitivity to
      terbinafine as Saccharomyces cerevisiae. The effect of terbinafine on neutral
      lipid pattern was tested at concentrations with low, moderate and strong growth
      inhibition (2.5, 5 and 7.5 MUg ml(-1) , respectively). Compared to S. cerevisiae,
      treatment with subinhibitory terbinafine doses had a weaker effect on steryl
      ester levels and total ergosterol levels in K. lactis. Quantification of squalene
      levels in terbinafine-treated K. lactis cells revealed high accumulation of
      squalene particularly in cells treated with 7.5 MUg ml(-1) terbinafine in lactose
      medium. Terbinafine treatment stimulated the development of lipid droplets as
      lipid storage organelles and this effect was different in K. lactis grown on
      glucose or lactose media. Present report is the first attempt to utilize lactose
      fermenting yeast K. lactis for production of a high-value lipid and it proves
      squalene epoxidase as a promising target for squalene overproduction in this
      yeast. SIGNIFICANCE AND IMPACT OF THE STUDY: Squalene is a natural substance with
      wide applications in food, cosmetic and pharmaceutic industries. The suitability
      of lactose-fermenting yeast Kluyveromyces lactis for the production of squalene
      was tested in the study. Partial inhibition of squalene epoxidase by specific
      inhibitor terbinafine resulted in high accumulation of squalene in K. lactis
      grown on glucose or lactose comparable to values found in terbinafine-treated
      Saccharomyces cerevisiae. Our results prove that K. lactis is a promising micro
      organism for genetic manipulations aimed at the production of squalene on
      industrial waste like whey as the growth substrate.

PMID- 25864716
TI  - Novel Programs, International Adoptions, or Contextual Adaptations? Meta
      Analytical Results From German and Swedish Intervention Research.
AB  - One of the major dilemmas in intervention and implementation research is
      adaptation versus adherence. High fidelity to an intervention protocol is
      essential for internal validity. At the same time, it has been argued that
      adaptation is necessary for improving the adoption and use of interventions by,
      for example, improving the match between an intervention and its cultural
      context, thus improving external validity. This study explores the origins of
      intervention programs (i.e., novel programs, programs adopted from other contexts
      with or without adaptation) in two meta-analytic intervention data sets from two
      European countries and compares the effect sizes of the outcomes of the
      interventions evaluated. Results are based on two samples of studies evaluating
      German child and youth preventative interventions (k = 158), and Swedish
      evaluations of a variety of psychological and social interventions (k = 139). The
      studies were categorized as novel programs, international adoption and contextual
      adaptation, with a total of six subcategories. In the German sample, after
      statistically controlling for some crucial methodological aspects, novel programs
      were significantly more effective than adopted programs. In the Swedish sample, a
      trend was found suggesting that adopted programs were less effective than adapted
      and novel programs. If these results are generalizable and unbiased, they favor
      novel and adapted programs over adopted programs with no adaptation and indicate
      that adoption of transported programs should not be done without considering
      adaptation.

PMID- 25864717
TI  - Pulmonary alveolar proteinosis: time to shift?
AB  - Pulmonary alveolar proteinosis (PAP) is categorized into hereditary, secondary
      and autoimmune PAP (aPAP) types. The common pathogenesis is the ability of the
      alveolar macrophages to catabolize phagocytized surfactant is affected.
      Hereditary PAP is caused by mutations involving the GM-CSF signaling,
      particularly in genes for the GM-CSF receptor and sometimes by GATA2 mutations.
      Secondary PAP occurs in hematologic malignancies, other hematologic disorders,
      miscellaneous malignancies, fume and dust inhalation, drugs, autoimmune disorders
      and immunodeficiencies. aPAP is related to the production of GM-CSF
      autoantibodies. PAP is characterized morphologically by the inappropriate and
      progressive 'occupation' of the alveolar spaces by an excessive amount of
      unprocessed surfactant, limiting gas exchange and gradually exhausting the
      respiratory reserve. Myeloid cells' immunity deteriorates, increasing the risk of
      infections. Treatment of PAP is based on its etiology. In aPAP, recent
      therapeutic advances might shift the treatment option from the whole lung lavage
      procedure under general anesthesia to the inhalation of GM-CSF 'as needed'.

PMID- 25864719
TI  - An anatomic explanation for combined so-called adventitial/intraneural cysts.

PMID- 25864720
TI  - Chimpanzees facing a dangerous situation: A high-traffic asphalted road in the
      Sebitoli area of Kibale National Park, Uganda.
AB  - Despite the spread of road infrastructures throughout Africa to support regional
      development, industry, and tourism, few studies have examined how wild animals
      adapt their behavior and ecology in road-forest ecotones. Indeed, while numerous
      studies have demonstrated chimpanzee adaptability in anthropogenic landscapes,
      none have examined the effects of asphalted highways on wild chimpanzee
      behaviors. In a 29-month survey, we assessed the dangers posed by an asphalted
      road crossing the Sebitoli area of Kibale National Park (Uganda). We analyzed 122
      individual chimpanzee crossings. Although the asphalted road represents a
      substantial threat to crossing animals (89 motorized vehicles per hour use this
      road and individuals of six different primate species were killed in 1 year),
      chimpanzees took into account this risk. More than 90% of the individuals looked
      right and left before and while crossing. Chimpanzees crossed in small subgroups
      (average 2.7 subgroups of 2.1 individuals per crossing event). Whole parties
      crossed more rapidly when chimpanzees were more numerous in the crossing groups.
      The individuals most vulnerable to the dangers of road crossing (females with
      dependents, immature, and severely injured individuals) crossed less frequently
      compared with non-vulnerable individuals (lone and healthy adolescents and
      adults). Moreover, healthy adult males, who were the most frequent crossing
      individuals, led progressions more frequently when crossing the road than when
      climbing or descending feeding trees. Almost 20% of the individuals that crossed
      paid attention to conspecifics by checking on them or waiting for them while
      crossing. These observations are relevant for our understanding of adaptive
      behavior among chimpanzees in human-impacted habitats. Further investigations are
      needed to better evaluate the effects of busy roads on adolescent female
      dispersal and on their use of territories. Mitigation measures (e.g., bridges,
      underpasses, reduced speed limits, speed-bumps, signposts, or police controls)
      should be established in this area.

PMID- 25864718
TI  - Inflammation and the depot-specific secretome of human preadipocytes.
AB  - OBJECTIVE: Visceral white adipose tissue (WAT) expansion and macrophage
      accumulation are associated with metabolic dysfunction. Visceral WAT typically
      shows greater macrophage infiltration. Preadipocytes show varying proinflammatory
      expression profiles among WAT depots. The objective was to examine the secretomes
      and chemoattractive properties of preadipocytes from visceral and subcutaneous
      WAT. METHODS: A label-free quantitative proteomics approach was applied to study
      secretomes of subcutaneous and omental preadipocytes from obese subjects. Enzyme
      linked immunosorbent assays and chemotaxis assays were used to confirm
      proinflammatory chemokine secretion between depots. RESULTS: Preadipocyte
      secretomes showed greater variation between depots than did intracellular protein
      expression. Chemokines were the most differentially secreted proteins. Omental
      preadipocytes induced chemoattraction of macrophages and monocytes. Neutralizing
      antibodies to the identified chemokines reduced macrophage/monocyte
      chemoattraction. Subcutaneous preadipocytes treated with interleukin-6 (IL-6)
      resembled omental preadipocytes in terms of chemokine secretion and
      macrophage/monocyte chemoattraction. Janus-activated kinase (JAK1/2) protein
      expression, which transduces IL-6 signaling, was higher in omental than
      subcutaneous preadipocytes and WAT. Inhibiting JAK in omental preadipocytes
      decreased chemokine secretion and macrophage/monocyte chemoattraction to levels
      closer to that observed in subcutaneous preadipocytes. CONCLUSIONS: Secretomes of
      omental and subcutaneous preadipocytes are distinct, with the former inducing
      more macrophage/monocyte chemoattraction, in part through IL-6/JAK-mediated
      signaling.

PMID- 25864721
TI  - GRIN1 mutations cause encephalopathy with infantile-onset epilepsy, and
      hyperkinetic and stereotyped movement disorders.
AB  - OBJECTIVE: Recently, de novo mutations in GRIN1 have been identified in patients
      with nonsyndromic intellectual disability and epileptic encephalopathy. Whole
      exome sequencing (WES) analysis of patients with genetically unsolved epileptic
      encephalopathies identified four patients with GRIN1 mutations, allowing us to
      investigate the phenotypic spectrum of GRIN1 mutations. METHODS: Eighty-eight
      patients with unclassified early onset epileptic encephalopathies (EOEEs) with an
      age of onset <1 year were analyzed by WES. The effect of mutations on N-methyl-D
      aspartate (NMDA) receptors was examined by mapping altered amino acids onto three
      dimensional models. RESULTS: We identified four de novo missense GRIN1 mutations
      in 4 of 88 patients with unclassified EOEEs. In these four patients, initial
      symptoms appeared within 3 months of birth, including hyperkinetic movements in
      two patients (2/4, 50%), and seizures in two patients (2/4, 50%). Involuntary
      movements, severe developmental delay, and intellectual disability were
      recognized in all four patients. In addition, abnormal eye movements resembling
      oculogyric crises and stereotypic hand movements were observed in two and three
      patients, respectively. All the four patients exhibited only nonspecific focal
      and diffuse epileptiform abnormality, and never showed suppression-burst or
      hypsarrhythmia during infancy. A de novo mosaic mutation (c.1923G>A) with a
      mutant allele frequency of 16% (in DNA of blood leukocytes) was detected in one
      patient. Three mutations were located in the transmembrane domain (3/4, 75%), and
      one in the extracellular loop near transmembrane helix 1. All the mutations were
      predicted to impair the function of the NMDA receptor. SIGNIFICANCE: Clinical
      features of de novo GRIN1 mutations include infantile involuntary movements,
      seizures, and hand stereotypies, suggesting that GRIN1 mutations cause
      encephalopathy resulting in seizures and movement disorders.

PMID- 25864723
TI  - Sedation vs. Intubation for Endovascular Stroke TreAtment (SIESTA) - a randomized
      monocentric trial.
AB  - BACKGROUND: The optimal peri-interventional management of sedation and airway for
      endovascular stroke treatment (EST) appears to be a crucial factor for treatment
      success. According to retrospective studies, the widely favored general
      anesthesia with intubation seems to be associated with poor functional outcome
      compared to a slightly sedated non-intubated condition (conscious sedation).
      METHOD: SIESTA is a monocentric, prospective, randomized parallel-group, open
      label treatment trial with blinded endpoint evaluation (PROBE design). The study
      compares the non-intubated with the intubated state in patients receiving
      endovascular treatment of acute ischemic anterior circulation stroke. The primary
      endpoint is early neurological improvement as by National Institutes of Health
      Stroke Scale (NIHSS) after 24 h (difference between NIHSS on admission and NIHSS
      after 24 h). Secondary endpoints include: functional outcome after three-months
      as by modified Rankin Scale (mRS), mortality, parameters of ventilation and
      critical care, feasibility, and safety, i.e. complications related to
      endovascular stroke treatment. CONCLUSION: The aims of this study are to
      prospectively clarify whether the non-intubated state of conscious sedation is
      feasible, safe, and superior with regard to early neurological improvement
      compared to the intubated state of general anesthesia in patients receiving acute
      endovascular stroke treatment.

PMID- 25864722
TI  - N-Terminally extended analogues of the K+ channel toxin from Stichodactyla
      helianthus as potent and selective blockers of the voltage-gated potassium
      channel Kv1.3.
AB  - The voltage-gated potassium channel Kv1.3 is an important target for the
      treatment of autoimmune diseases and asthma. Blockade of Kv1.3 by the sea anemone
      peptide K+-channel toxin from Stichodactyla helianthus (ShK) inhibits the
      proliferation of effector memory T lymphocytes and ameliorates autoimmune
      diseases in animal models. However, the lack of selectivity of ShK for Kv1.3 over
      the Kv1.1 subtype has driven a search for Kv1.3-selective analogues. In the
      present study, we describe N-terminally extended analogues of ShK that contain a
      negatively-charged Glu, designed to mimic the phosphonate adduct in earlier Kv1.3
      selective analogues, and consist entirely of common protein amino acids.
      Molecular dynamics simulations indicated that a Trp residue at position [-3] of
      the tetrapeptide extension could form stable interactions with Pro377 of Kv1.3
      and best discriminates between Kv1.3 and Kv1.1. This led to the development of
      ShK with an N-terminal Glu-Trp-Ser-Ser extension ([EWSS]ShK), which inhibits
      Kv1.3 with an IC50 of 34 pm and is 158-fold selective for Kv1.3 over Kv1.1. In
      addition, [EWSS]ShK is more than 2900-fold more selective for Kv1.3 over Kv1.2
      and KCa3.1 channels. As a highly Kv1.3-selective analogue of ShK based entirely
      on protein amino acids, which can be produced by recombinant expression, this
      peptide is a valuable addition to the complement of therapeutic candidates for
      the treatment of autoimmune diseases.

PMID- 25864724
TI  - Acute and chronic ecotoxicological effects of four pharmaceuticals drugs on
      cladoceran Daphnia magna.
AB  - The occurrence of pharmaceuticals in the aquatic environment has received
      increasing attention in recent years, as concerns have risen about their
      environmental persistence, biological activity and different effects toward
      nontarget organisms. Considering the magnitude of concentrations (ng L(-1) to mg
      L(-1)) and their often-specific modes of action, the assessment of physiological
      responses of exposed aquatic biota may provide significant information regarding
      the potential ecological consequences of exposure to these contaminants. The
      present study intended to assess the acute and chronic effects of four
      pharmaceuticals: acetaminophen, chlorpromazine, diclofenac sodium and propranolol
      in the cladoceran species Daphnia magna. Parameters such as immobility, total of
      offspring and rate of population increase were analyzed. Results of acute
      exposures showed a considerable variability of toxicity among pharmaceuticals,
      with the following ranking of toxicity: diclofenac (EC50 = 123.3 mg L(-1)) <
      propranolol (EC50 = 5.531 mg L(-1)) < acetaminophen (EC50 = 2.831 mg L(-1)) <
      chlorpromazine (EC50 = 1.805 mg L(-1)). The chronic toxicity data showed the
      exertion of reproductive adverse effects. The compounds chlorpromazine and
      propranolol caused a significant decrease in fecundity, and the rate of
      population increase parameter suffered a significant decrease from 0.33 mg L(-1)
      to 0.128 mg L(-1) onwards, respectively. The levels of exposure to which our test
      organism was acutely and chronically exposed were above those already reported in
      the wild. Nevertheless, the extensive production, prescription and release of
      pharmaceuticals drugs will continue to grow in the future, and consequently their
      loadings to the environment can result in potential long-term ecological risks to
      aquatic biota.

PMID- 25864725
TI  - Over the horizon - future innovations in global urology.

PMID- 25864726
TI  - Controllable Synthesis of Bandgap-Tunable CuSx Se(1-x) Nanoplate Alloys.
AB  - Composition engineering is an important approach for modulating the physical
      properties of alloyed semiconductors. In this work, ternary CuS(x)Se(1-x)
      nanoplates over the entire composition range of 0<=x<=1 have been controllably
      synthesized by means of a simple aqueous solution method at low temperature (90 
      degrees C). Reaction of Cu(2+) cations with polysulfide/-selenide ((S(n)Se(m))(2
      )) anions rather than independent S(n)(2-) and Se(m)(2-) anions is responsible
      for the low-temperature and rapid synthesis of CuS(x)Se(1-x) alloys, and leads to
      higher S/Se ratios in the alloys than that in reactants owing to different
      dissociation energies of the Se-Se and the S-S bonds. The lattice parameters 'a'
      and 'c' of the hexagonal CuS(x)Se(1-x) alloys decrease linearly, whereas the
      direct bandgaps increase quadratically along with the S content. Direct bandgaps
      of the alloys can be tuned over a wide range from 1.64 to 2.19 eV. Raman peaks of
      the S-Se stretching mode are observed, thus further confirming formation of the
      alloyed CuS(x)Se(1-x) phase.

PMID- 25864727
TI  - Nonsuturing or Skin Adhesives versus Suturing of the Perineal Skin After
      Childbirth: A Systematic Review.
AB  - BACKGROUND: Suturing of perineal trauma after childbirth can cause problems such
      as pain, discomfort because of tight sutures, the need for suture removal, and
      dyspareunia. It is unclear whether leaving the perineal skin unsutured or using
      skin adhesives might prevent these problems. METHODS: CENTRAL, MEDLINE, EMBASE,
      CINAHL, and prospective trial registers until January 2013 were searched for
      (quasi-)randomized controlled trials comparing nonsuturing of the perineal skin
      or skin adhesives versus suturing of the skin when repairing a second-degree
      perineal tear or episiotomy. Primary outcome measure was short-term and long-term
      pain and need for analgesic medication. RESULTS: Four randomized and two quasi
      randomized controlled trials (involving 2,922 women) with heterogeneity in
      contexts, designs, and methodological quality were included. Nonsuturing of the
      skin leads to less short-term and long-term pain compared to suturing and an
      increased rate of skin separation. Skin adhesives lead to less short-term pain
      without an increased rate of skin separation. Nonsuturing or skin adhesives lead
      to less complaints and there are no other adverse effects. CONCLUSIONS:
      Nonsuturing of the skin or the use of skin adhesives appears preferable in terms
      of pain. Nonsuturing could lead to more short-term skin separation when no
      adhesives are used, but there is no evidence for the clinical importance of skin
      separation. There is a need for studies with a follow-up of at least 6 months, in
      which pain is measured homogeneously and for studies comparing the use of skin
      adhesives with nonsuturing of the skin with the focus on long-term cosmetic
      results.

PMID- 25864728
TI  - Age-related changes in resting-state networks of a large sample size of healthy
      elderly.
AB  - AIMS: Population aging is burdening the society globally, and the evaluation of
      functional networks is the key toward understanding cognitive changes in normal
      aging. However, the effect of age on default mode subnetworks has not been
      documented well, and age-related changes in many resting-state networks remain
      debatable. The purpose of this study was to propose more precise results for
      these issues using a large sample size. METHODS: We used group-level meta-ICA
      analysis and dual regression approach for identifying resting-state networks from
      functional magnetic resonance imaging data of 430 healthy elderly participants.
      Partial correlation was used to observe age-related correlations within and
      between resting-state networks. RESULTS: In the default mode network, only the
      ventral subnetwork negatively correlated with age. Age-related decrease in
      functional connectivity was also noted in the auditory, right frontoparietal,
      sensorimotor, and visual medial networks. Further, some age-related increases and
      decreases were observed for between-network correlations. CONCLUSION: The results
      of this study suggest that only the ventral default mode subnetwork had age
      related decline in functional connectivity and several reverse patterns of
      resting-state networks for network development. Understanding age-related network
      changes may provide solutions for the impact of population aging and diagnosis of
      neurodegenerative diseases.

PMID- 25864729
TI  - In response to "Development, implementation and impact of an automated early
      warning and response system for sepsis".

PMID- 25864730
TI  - Negative thermal expansion in functional materials: controllable thermal
      expansion by chemical modifications.
AB  - Negative thermal expansion (NTE) is an intriguing physical property of solids,
      which is a consequence of a complex interplay among the lattice, phonons, and
      electrons. Interestingly, a large number of NTE materials have been found in
      various types of functional materials. In the last two decades good progress has
      been achieved to discover new phenomena and mechanisms of NTE. In the present
      review article, NTE is reviewed in functional materials of ferroelectrics,
      magnetics, multiferroics, superconductors, temperature-induced electron
      configuration change and so on. Zero thermal expansion (ZTE) of functional
      materials is emphasized due to the importance for practical applications. The NTE
      functional materials present a general physical picture to reveal a strong
      coupling role between physical properties and NTE. There is a general nature of
      NTE for both ferroelectrics and magnetics, in which NTE is determined by either
      ferroelectric order or magnetic one. In NTE functional materials, a multi-way to
      control thermal expansion can be established through the coupling roles of
      ferroelectricity-NTE, magnetism-NTE, change of electron configuration-NTE, open
      framework-NTE, and so on. Chemical modification has been proved to be an
      effective method to control thermal expansion. Finally, challenges and questions
      are discussed for the development of NTE materials. There remains a challenge to
      discover a "perfect" NTE material for each specific application for chemists. The
      future studies on NTE functional materials will definitely promote the
      development of NTE materials. 

PMID- 25864731
TI  - Long-term local disease control in a recurrent soft-tissue sarcoma of the thigh
      treated by radiofrequency ablation.
AB  - In 2008, we performed radiofrequency ablation (RFA) in an elderly patient with a
      large recurrent soft-tissue sarcoma of the thigh, previously treated with surgery
      and radiotherapy. After ablation, a marked shrinkage of tumor was obtained.
      Further local recurrences occurred during follow-up, all safely treated by RFA,
      with local control of the disease maintained until 6-year follow-up. RFA was
      safe, effective, and repeatable for soft-tissue sarcoma recurrences, and allowed
      long-term local control of the disease.

PMID- 25864733
TI  - Expanded criteria donor kidneys for retransplantation United Network for Organ
      Sharing update: proceed with caution.
AB  - This study analyzed outcomes of retransplantation from expanded criteria donors
      (ECD) over the last two decades to determine the benefits and risks of using ECD
      kidneys for retransplantation. Data from the United Network for Organ Sharing
      database were collected and analyzed. Graft survival, death-censored graft
      survival, and patient survival for retransplantation with ECD kidneys (re-ECD)
      were reported and compared with primary transplantation with ECD kidneys (prim
      ECD) and retransplantation with standard criteria donor kidneys (re-SCD). Re-ECD
      kidneys had higher risk of graft failure compared with prim-ECD (hazard ratio
      [HR] = 1.19) and to re-SCD (HR = 1.76). Patient survival was better in re-ECD
      compared with prim-ECD (HR = 0.89) but was worse than re-SCD (HR = 1.82). After
      censoring the patients who died with a functioning graft, re-ECD had a higher
      mortality risk compared with prim-ECD (HR = 1.45) and re-SCD (HR = 1.79).
      Transplantation improves quality of life and reduces healthcare costs, and due to
      the risk associated with resumption of hemodialysis and the longer waiting list
      times for SCD kidneys, there is a benefit to accepting ECD kidneys for select
      patients requiring retransplantation. Although this benefit exists for select
      patients, retransplantation with ECD kidneys should be undertaken with
      trepidation, and appropriate informed consent should be obtained. 

PMID- 25864734
TI  - Representativeness of laboratory sampling procedures for the analysis of trace
      metals in soil.
AB  - This study was conducted to assess the representativeness of laboratory sampling
      protocols for purposes of trace metal analysis in soil. Five laboratory protocols
      were compared, including conventional grab sampling, to assess the influence of
      sectorial splitting, sieving, and grinding on measured trace metal concentrations
      and their variability. It was concluded that grinding was the most important
      factor in controlling the variability of trace metal concentrations. Grinding
      increased the reproducibility of sample mass reduction by rotary sectorial
      splitting by up to two orders of magnitude. Combined with rotary sectorial
      splitting, grinding increased the reproducibility of trace metal concentrations
      by almost three orders of magnitude compared to grab sampling. Moreover, results
      showed that if grinding is used as part of a mass reduction protocol by sectorial
      splitting, the effect of sieving on reproducibility became insignificant. Gy's
      sampling theory and practice was also used to analyze the aforementioned sampling
      protocols. While the theoretical relative variances calculated for each sampling
      protocol qualitatively agreed with the experimental variances, their quantitative
      agreement was very poor. It was assumed that the parameters used in the
      calculation of theoretical sampling variances may not correctly estimate the
      constitutional heterogeneity of soils or soil-like materials. Finally, the
      results have highlighted the pitfalls of grab sampling, namely, the fact that it
      does not exert control over incorrect sampling errors and that it is strongly
      affected by distribution heterogeneity. 

PMID- 25864732
TI  - Belinostat, a potent HDACi, exerts antileukaemic effect in human acute
      promyelocytic leukaemia cells via chromatin remodelling.
AB  - Epigenetic changes play a significant role in leukaemia pathogenesis, therefore
      histone deacetylases (HDACis) are widely accepted as an attractive strategy for
      acute promyelocytic leukaemia (APL) treatment. Belinostat (Bel, PXD101), a
      hydroxamate-type HDACi, has proved to be a promising cure in clinical trials for
      solid tumours and haematological malignancies. However, insight into molecular
      effects of Bel on APL, is still lacking. In this study, we investigated the
      effect of Bel alone and in combination with differentiation inducer retinoic acid
      (RA) on human promyelocytic leukaemia NB4 and HL-60 cells. We found that
      treatment with Bel, depending on the dosage used, inhibits cell proliferation,
      whereas in combination with RA enhances and accelerates granulocytic leukaemia
      cell differentiation. We also evaluated the effect of used treatments with Bel
      and RA on certain epigenetic modifiers (HDAC1, HDAC2, PCAF) as well as cell cycle
      regulators (p27) gene expression and protein level modulation. We showed that Bel
      in combination with RA up-regulates basal histone H4 hyperacetylation level more
      strongly compared to Bel or RA alone. Furthermore, chromatin immunoprecipitation
      assay indicated that Bel induces the accumulation of hyperacetylated histone H4
      at the p27 promoter region. Mass spectrometry analysis revealed that in control
      NB4 cells, hyperacetylated histone H4 is mainly found in association with
      proteins involved in DNA replication and transcription, whereas after Bel
      treatment it is found with proteins implicated in pro-apoptotic processes, in
      defence against oxidative stress and tumour suppression. Summarizing, our study
      provides some novel insights into the molecular mechanisms of HDACi Bel action on
      APL cells. 

PMID- 25864735
TI  - Effects of sludge recirculation rate and mixing time on performance of a
      prototype single-stage anaerobic digester for conversion of food wastes to biogas
      and energy recovery.
AB  - Food wastes have been recognized as the largest waste stream and accounts for
      39.25 % of total municipal solid waste in Thailand. Chulalongkorn University has
      participated in the program of in situ energy recovery from food wastes under the
      Ministry of Energy (MOE), Thailand. This research aims to develop a prototype
      single-stage anaerobic digestion system for biogas production and energy recovery
      from food wastes inside Chulalongkorn University. Here, the effects of sludge
      recirculation rate and mixing time were investigated as the main key parameters
      for the system design and operation. From the results obtained in this study, it
      was found that the sludge recirculation rate of 100 % and the mixing time of 60
      min per day were the most suitable design parameters to achieve high efficiencies
      in terms of chemical oxygen demand (COD), total solids (TS), and total volatile
      solid (TVS) removal and also biogas production by this prototype anaerobic
      digester. The obtained biogas production was found to be 0.71 m(3)/kg COD and the
      composition of methane was 61.6 %. Moreover, the efficiencies of COD removal were
      as high as 82.9 % and TVS removal could reach 83.9 % at the optimal condition.
      Therefore, the developed prototype single-stage anaerobic digester can be highly
      promising for university canteen application to recover energy from food wastes
      via biogas production. 

PMID- 25864736
TI  - Can vitamin a mediate immunity and inflammation?
AB  - Vitamins are natural components of foods and are organic compounds distinct from
      fat, carbohydrates and proteins. Vitamin A is the generic descriptor for
      compounds with the qualitative biological activity of retinol. Unlike beta
      carotene, vitamin A is not an antioxidant and its benefit is related to possible
      boosting of immune reactions. The effect of vitamin A on immune function is wide
      reaching and its deficiency appears to affect immunity in several ways. Innate
      and adaptive immune responses are affected in some way by lack of vitamin A.
      Retinoids seem to act on differentiation of lymphocytes, antibody production,
      phagocytosis of macrophages, NK, Treg, and T helper cell activity. In addition,
      in humans, signs of a vitamin A deficiency also include the dysregulation of
      cytokine/chemokine generation and release. However, excess of vitamin A has been
      demonstrated to have toxic effects in most species studied. Here we summarize
      some important effects of vitamin A in immunity and inflammation. 

PMID- 25864737
TI  - Development of two salmonella-based oral vaccines against human respiratory
      syncytial virus.
AB  - Human respiratory syncytial virus is the most common cause of bronchiolitis and
      other respiratory infections in infants and the elderly worldwide. We have
      developed two new oral vaccines using Salmonella typhi TY21a to carry and express
      the immunogenic epitopes of RSV fusion (F) and attachment (G) glycoproteins on
      its surface, separately. To evaluate the efficacy of the designed vaccines,
      BALB/c mice were orally immunized and then infected with RSV. Immune response
      analyses showed that cellmediated, mucosal and humoral immunity in the vaccinated
      mice were significantly enhanced compared to the control group. Both vaccines
      generated a balanced Th1/Th2 immune response which is crucial for efficiency of
      vaccines against RSV. Furthermore, histopathological examination proved that
      these vaccines were safe as they did not cause any Th2-associated adverse effects
      in the lungs of RSV-infected mice. The findings of this research suggest that
      Salmonella-F and Salmonella-G vaccine candidates may have strong potential to
      prevent RSV infection. 

PMID- 25864738
TI  - Probing head-to-toe deformation law assessment for abdominal tumor through
      respiratory movement simulation and CTVision radiation research.
AB  - This paper aims to explore head-to-toe deformation law for abdominal tumor with
      CTVision and selfdesigned respiratory movement simulation mold and meanwhile
      verify the accuracy and correctness of the treatment. In experimental group, a
      self-designed respiratory movement mold was used. The image was scanned out by CT
      scanning based on the movement state and then sent to the planning system to
      compare the location variation of tumor and formulating the treatment plan
      accordingly, followed by verification and verified derivation values observation.
      A total of 21 cases of abdominal tumor were included in the case group. Their
      breathing movement was detected under a simulated locator and then the data was
      recorded. The image was scanned and sent to the planning system to compare the
      location variation of the tumor, the patients then underwent 3D conformal therapy
      (3D-CRT) and we performed verification and observed verified derivation values.
      Finally, the results of the case group and the experimental group were compared.
      The mean of the verified derivation values was smaller than respiratory motion
      values in experimental group (t=-10.78, P=0, P < 0.05); the mean of verified
      derivation values of the patients was smaller than respiratory motion values in
      group f, g, h, i, j, l, n, o, p, q, r, s t, u in the case group (P < 0.05); no
      remarkable difference was found between the two values in group a, b, c, k and m
      (P < 0.05); group e was unable to undergo the statistical test since its standard
      deviation was 0; the mean of the verified derivation values was higher than
      respiratory motion values in group d (P < 0.05). In conclusion, radiation therapy
      applied with CTVision proved to be accurate and convincing in the treatment of
      abdominal tumor.

PMID- 25864739
TI  - The inflammatory milieu and the insulin like growth factor axis in children with
      inflammatory bowel disease following recombinant human growth hormone treatment.
AB  - It is unclear whether recombinant human growth hormone (rhGH) in inflammatory
      bowel disease (IBD) alters cytokine profile. The objective of this study is to
      evaluate changes in cytokines and systemic markers of the insulin growth factor
      axis following 6 months of rhGH treatment in children with IBD. In a six-month
      randomised control trial in children with IBD treated with rhGH at 0.067
      mg/kg/day and controls (11 in each group), we measured pro-, anti-inflammatory
      cytokines and systemic markers of the IGF axis (total IGF-1, free IGF-1, total
      IGFBP-3, ALS, IGFBP-2) at baseline (T+0), and six months (T+6). Results expressed
      as median (range). In the rhGH group, TNFalpha was 3.1pg/ml (2.9, 100.6) and
      3.6pg/ml (3.1, 5.3) at T+0 and T+6, respectively (p=0.85), whereas in the
      controls this was 3.3pg/ ml (2.7, 4.0) and 3.1pg/m l (2.7, 4.7), respectively
      (p=0.79). In the rhGH group, IL1beta was 18.0pg/ml (5.0,716.7) and 18.0pg/ml
      (1.7, 52.2) at T+0 and T+6 respectively(p=0.90), whereas in the controls this was
      19.8pg/ml (4.1, 27.1) and 19.1pg/ml (2.4,77.3), respectively (p=0.65). None of
      the twenty-eight other cytokines analysed was different at T+6 in either group.
      Despite increase in total IGF1 in the rhGH group (p=0.03), free IGF1, IGFBP3, ALS
      and IGFBP2 did not change in either group at T+6. Percentage change in IGFBP3,
      was significantly associated with percentage change in IL2 (r=0.77, p=0.009) and
      IL4 (r=0.58, p=0.01). Percentage change in ALS was significantly associated with
      percentage change in IL2 (r=0.90, p less than 0.0001) and IL4 (r=0.63, p=0.04).
      Although changes in markers of the GH/IGF-1 axis do show an association with
      cytokines (IL-2, IL-4) in pediatric IBD, six months of rhGH treatment was not
      associated with any significant changes in levels of a range of pro and anti
      inflammatory cytokine. Careful evaluation of disease process is required in
      future trials of rhGH in paediatric IBD. 

PMID- 25864740
TI  - Association between progesterone and estradiol-17beta treatment and protein
      expression of pgr and PGRMC1 in porcine luminal epithelial cells: a real-time
      cell proliferation approach.
AB  - The correct functionality (sensitivity and receptivity) of endometrial tissue is
      regulated by paracrine and endocrine pathways that activate several mediators or
      metabolic pathways and gene cascades. This study aimed to investigate the
      influence of E2 and P4 on progesterone receptor (PGR) and progesterone receptor
      membrane component 1 (PGRMC1) protein expression in porcine luminal epithelial
      cells and their influence on the proliferation of these cells in real-time.
      Surface uterine luminal epithelial cells were removed using sterile surgical
      blades from uterine horns of ten crossbred anestrus gilts. Following treatment
      with collagenase I, cells were separated and transferred into 48-well E-Plates
      for use in a realtime cell analyzer (RTCA). The luminal epithelial cells were
      cultured in vitro (IVC) in standard DMEM cell culture medium and incubated with
      E2 (10 pg/ml, 40 pg/ml, 500 pg/ml) and P4 (10 ng/ml, 40 ng/ ml, 500 ng/ml). The
      cell proliferation index was analyzed after 0-240 h, 0-120 h, 120-240 h. After
      using the RTCA analysis we found increased proliferation of luminal epithelial
      cells after treatment of low doses of P4 (10 and 40 ng/ml), (P < 0.001). Higher
      doses of P4 led to decrease of proliferation (P < 0.001). Conversely, higher
      doses of E2 (500 pg/ml) increased the proliferation index as compared to low
      doses (10 pg/ml) and control (P < 0.001). Confocal microscopic observations
      revealed that higher concentrations of E2 upregulate the expression of both PGR
      and PGRMC1. Additionally, P4 used in lower concentrations stimulated the
      expression of these receptors, too. Our study presents a new influence of E2 and
      P4 on the expression of PGR and PGRMC1 and on the real-time proliferation of
      porcine luminal epithelial cells. The relationship between PGR or PGRMC1
      expression and the proliferation of luminal epithelial cells may be influenced
      (up- or down regulated) by E2 or P4 in a steroid type- and dose-dependent manner.

PMID- 25864741
TI  - Biomarkers for the evaluation of immunological properties during the shikoku
      walking pilgrimage.
AB  - It is important to determine the immunological properties for the maintenance of
      health. We chose the Shikoku Walking Pilgrimage to assess the proper biomarkers
      for the evaluation of immunological properties. We examined whether the Shikoku
      Walking Pilgrimage could have a positive effect on the mental and physical health
      of walking participants by using several biomarkers proposed by our laboratory.
      Twelve non-randomized healthy male volunteers including 3 twice attendees walked
      the Shikoku Walking Pilgrimage distance of 58.9 km over 3 days. Plasma, serum,
      urine, and saliva were collected from the volunteers during the pilgrimage and at
      1 week before and after it. Immunological biomarkers, including lipid metabolism,
      oxidative stress, immune function, and catecholamines, were measured.
      Additionally, mood state scores, alertness, autonomic nervous system activity,
      and body motion levels during sleep were assessed. A significant decrease was
      observed in the subjective tension-anxiety levels and in the concentrations of
      serum low-density lipoprotein cholesterol, plasma hydroxyoctadecadienoic acid
      (HODE), and urine adrenaline during the pilgrimage as compared to the values of
      these parameters before the participants embarked on the pilgrimage. The serum
      levels of brain-derived neurotrophic factor (BDNF) were significantly increased 1
      week after the pilgrimage relative to those assessed previously. No significant
      differences in subjective fatigue and the flicker perception threshold were
      observed. These results suggest that the Shikoku Walking Pilgrimage can exert a
      positive effect on mental and physical health as particularly shown in the
      reduction of tensionanxiety and oxidative stress without the accompaniment of
      fatigue. HODE correlated significantly with typical immunological marker natural
      killer cell activity and immunoglobulin G. This suggests that there are promising
      biomarkers such as HODE, NK activity, BDNF, LDL-c, and IgG for assessing the
      immunological properties. 

PMID- 25864742
TI  - Effect of trimetazidine on serum interleukin-6 and C-reactive protein
      concentrations in patients with stable coronary artery disease.
AB  - Trimetazidine is widely used in the treatment of stable coronary artery disease
      (CAD) and its cytoprotective effect has been confirmed in animal studies and in
      many clinical trials. Given the inflammatory milieu of CAD and trimetazidine
      effect on the inflow of neutrophilis to the ischemic area, it is interesting to
      consider whether trimetazidine actions could be also explained through the
      inhibition of inflammatory mediators, including cytokines. The aim of this study
      was to (i) examine the influence of treadmill exercise test (TET) on serum C
      reactive protein (CRP) and interleukin-6 (IL-6), and (ii) the influence of three
      month trimetazidine therapy on serum CRP and IL-6 concentrations. One hundred and
      fifty-six patients with stable CAD were included. TET was performed (according to
      the standard Bruce protocol) twice for all subjects ? at baseline and after the
      three-month trimetazidine treatment. Serum IL-6 and CRP concentrations were
      determined prior to and after performing each TET. Exercise led to the increase
      of CRP (2.35 vs 2.81 mg/L, p < 0.05) and IL-6 concentrations (1.64 vs 1.92 pg/ml,
      p=0.0318) in patients without trimetazidine. Three-month treatment resulted in
      the increase in the TET duration (378.0s vs 410.9s, p < 0.05) and decrease in
      serum CRP concentration, both before (2.35 vs 1.51 mg/L, p < 0.05) and after TET
      (2.81 vs 1.69 mg/L, p < 0.05). There was no significant increase of CRP after the
      second TET (1.51 vs 1.69 mg/l, p=NS). Three-month trimetazidine treatment
      increased IL-6 concentrations (1.64 vs 2.23 pg/mL, p < 0.05). TET was not
      associated with further changes in IL-6 concentrations (2.23 vs 2.18 pg/mL,
      p=NS). Serum IL-6 and CRP concentrations increase during exercise in patients
      without trimetazidine. Three-month trimetazidine prolonged the duration of TET.
      Moreover, it resulted in the reduction of CRP concentration The increase of IL-6
      concentration after three-month trimetazidine treatment and the lack of changes
      of its concentration after TET is associated with yet another mechanism of
      trimetazidine.

PMID- 25864743
TI  - Methyl mercaptan and hydrogen sulfide products stimulate proinflammatory
      cytokines in patients with necrotic pulp tissue and endodontically treated teeth.
AB  - Bacterial infections of the residual dentin or infected pulp tissue are
      responsible for most cases of endodontic treatment failures. Persisting
      microorganisms in necrotic pulp tissue produce sulphur components such as methyl
      mercaptan and hydrogen sulfide as well as thioether derivatives. Although there
      is emerging evidence that these sulphur compounds stimulate immune cells and
      induce the inflammatory cascade, the immunological mechanisms of local and
      systemic inflammation have not been described. In this retrospective study we
      evaluated the ex-vivo immune response of peripheral blood mononuclear cells to
      sulphur compounds in 53 patients with clinical or radiologic endodontic treatment
      failure, 20 patients with clinical discomfort or radiological findings without
      previous endodontic treatment and a control group of 31 patients who had received
      successful endodontic treatment at least five years previously. Patients with
      endodontic abnormalities showed significantly higher ex-vivo sulphur compound
      stimulated interferon-gamma (IFN-gamma) and interleukin-10 (IL-10) levels as
      compared to the control group. The association between ex-vivo-stimulated
      cytokines and endodontically derived sulphur compounds was further substantiated
      by the fact that the number of IFN-gamma and/or IL-10-positive patients decreased
      significantly 3-8 months after re-treatment of the root canal or tooth
      extraction. Furthermore, serum tumor necrosis factor-alpha (TNF-alpha) levels
      were higher in patients than in controls, and at the same time, the TNFA -308 G/A
      polymorphism was associated with endodontic treatment failure in our study
      population. We conclude that a cellular immune response to sulphur compounds
      contributes to the inflammatory process observed in relation to endodontic
      treatment failures. 

PMID- 25864744
TI  - Silencing of stat4 gene inhibits cell proliferation and invasion of colorectal
      cancer cells.
AB  - Signal transducers and activators of transcription (STAT) play critical roles in
      development, proliferation, and immune defense. However the consequences of STAT
      hyperactivity can predispose to diseases, including colorectal cancer. In the
      present study, we aimed to evaluate the function of STAT4 in human colorectal
      cancer (CRC). The expression of STAT4 was examined by immunohistochemical assay
      using a tissue microarray procedure. A loss-of-function experiment was carried
      out to investigate the effects of lentivirus-mediated STAT4 shRNA (Lv-shSTAT4) on
      cell proliferation and invasive potential indicated by MTT and Transwell assays
      in CRC cell lines (SW480 and Caco2). As a consequence, it was found that the
      expression of STAT4 protein was significantly increased in CRC tissues compared
      with that in adjacent non-cancerous tissues (ANCT) (71.1% vs 44.4%, P=0.015), and
      was related with the Duke?s staging and depth of invasion in CRC patients
      (P=0.022; P=0.001). Silencing of STAT4 gene suppressed cell proliferation and
      invasion of CRC cells. Taken together, these findings demonstrate that increased
      expression of STAT4 is positively correlated with the depth of invasion in CRC
      patients, and inhibition of STAT4 expression represses the growth and invasion of
      CRC cells, suggesting that STAT4 may be a promising therapeutic target for the
      treatment of CRC. 

PMID- 25864745
TI  - Efficacy of a food supplement in patients with hashimoto thyroiditis.
AB  - Thyroid inflammation has been commonly seen in recent decades, due to a series of
      factors and is considered as the most frequent thyroid illness. It is
      characterized by some distinctive traits, which include morphological and
      hormonal modifications, often in association with an elevated anti-thyroid
      autoantibody title. The aim of the therapy is to improve symptoms as fast as
      possible, treating inflammation and subsequent hypothyroidism, when present.
      Therefore, we evaluated the efficacy of a Food Supplement (FS) containing enzymes
      which is commonly used in various inflammatory processes and is able to modulate
      immune reactions during inflammation in a very rapid and efficacious way. An
      open, controlled study was then designed and 45 patients with Hashimoto
      thyroiditis were enrolled and divided into 3 groups (FS alone; thyroid hormones
      alone; FS plus thyroid hormones). Blood, morphological and subjective parameters
      were considered. The results obtained indicate that the FS used in our study is
      efficacious and safe when used alone and/or in combination with thyroid hormones
      in the treatment of autoimmune thyroiditis, as documented by the improvement of
      the majority of the parameters considered. The efficacy was considered faster
      than thyroid hormones alone as far as subjective symptomatology is considered. In
      conclusion, the use of the food supplement evaluated herein during inflammation
      may be considered an additional tool in clinicians? hands, when facing patients
      with autoimmune thyroiditis, especially in presence of subjective symptomatology,
      in order to rapidly alleviate it. 

PMID- 25864746
TI  - A cytotoxic analysis of a sardinian plant extract cream on human oral primary
      cell cultures: an in vitro study.
AB  - Wound healing agents support the natural healing process, reduce trauma and
      likelihood of secondary infections and hasten wound closure. The aim of this work
      was to evaluate the effect of different concentration of a new Sardinian plant
      cream (RD7) on two human primary cultures: Periodontal Ligament Stem Cells
      (hPDLSCs) and Gingival Fibroblasts (hGFs) derived from oral tissues in terms of
      morphological changes, cell proliferation and wound healing properties. RD7, is
      an interactive dressing containing phytocomplex derived from Sardinian endemic or
      not, medicinal plant extracts, with an important anti-radical, anti-inflammatory
      and antiseptic activity finalized to rapidly promote tissue regeneration and the
      formation of granulation tissue. hPDLSCs and hGFs were seeded at different
      concentrations (0.5, 1, 2.5 and 5 mg/ml) of RD7. The cell proliferation and
      viability was evaluated using colorimetric assays (MTT assay) and trypan blue
      exclusion test. Meanwhile, the morphological cell changes were evaluated by means
      of optic (OM) and scanning electronic microscopes (SEM). The induction of the
      migratory properties was evaluated by means of wound healing assay. In vitro
      results, using hPDLSCs and hGFs, showed a decrease of cell growth starting at 24
      h of incubation, at high concentrations (2.5 mg/ml and 5 mg/ml). This cell growth
      reduction was associated to evident morphological changes, whilst, at low
      concentrations (0.5 and 1 mg/ml) a typical unchanged morphology of both hPDLSCs
      and hGFs was shown. Wound healing assay showed a complete wound full closure
      occurring after 24 h of treatment in samples treated with low concentration of
      RD7. The results of the present work indicate that low concentrations of RD7 have
      no cytotoxicity effect, stimulate cell proliferation and contribute to induce the
      migratory properties in hPDLSCs and hGFs, therefore it could be considered a new
      product for use in clinical practice. 

PMID- 25864747
TI  - Bortezomib-induced peripheral neurotoxicity in human multiple myeloma-bearing
      mice.
AB  - The proteasome inhibitor bortezomib is an antineoplastic drug mainly used for the
      treatment of multiple myeloma (MM). Despite its effectiveness, bortezomib
      clinical use is often limited by the onset of peripheral neuropathy (BiPN). To
      better understand the mechanisms of BiPN several rat and mice models have been
      proposed, but no studies in MM-bearing animals allowing to test the antitumor
      activity of the selected schedules and the role of MM by itself in peripheral
      nervous system damage have been reported to date. Here, we carried out a study
      using immunodeficient C.B-17/Prkdcscid (SCID) mice injected with RPMI8266 human
      MM cells and treated with bortezomib 1 mg/kg once a week for five weeks. Animals
      were assessed with neurophysiological, behavioral and pathological methods and
      tumor volume measurement was performed along the study. At the end of the study
      BiPN was evident in bortezomib-treated animals, and this neurotoxic effect was
      evident using a schedule able to effectively prevent tumor growth. However,
      neurophysiological and pathological evidence of MM induced peripheral nervous
      system damage was also reported. This model based on MM-bearing animals is more
      reliable in the reproduction of the clinical setting and it is, therefore, more
      suitable than the previously reported models of BiPN to study its pathogenesis.
      Moreover, it represents an optimal model to test the efficacy of neuroprotective
      agents and at the same time their non-interference with bortezomib antineoplastic
      activity.

PMID- 25864748
TI  - Transcriptional activity of neutrophils exposed to high doses of colchicine:
      short communication.
AB  - Colchicine is an antimitotic drug which binds to tubulin and at high doses
      results in cytoskeleton disruption. Colchicine is believed to be an anti
      inflammatory agent, though its modulatory effects on the level and
      transcriptional activity of genes is still a matter of debate. There is growing
      evidence that alterations in the cytoskeleton exert specific effects on the
      expression of various genes. This study was undertaken to analyze whether
      disrupting the microtubule cytoskeleton by colchicine modulates transcriptional
      levels of MEFV, NF-kappaB p65, NLRP3, HMGB1, and caspase-3 in neutrophils from
      patients with familial Mediterranean fever (FMF) and healthy subjects. In the
      present study, colchicine caused increased expression of NLRP3 (p=0.007) and MEFV
      (p=0.03), but had no effect on caspase-3, NF-kappaB p65 and HMGB1 genes in
      healthy neutrophils. FMF neutrophils were less responsive to the drug treatment.
      This study supports the hypothesis that, being an anti-inflammatory agent,
      colchicine at relatively high concentrations might lead to the activation of pro
      inflammatory signalling pathways in neutrophils. 

PMID- 25864749
TI  - Clinical research on neuroblastoma based on serum lactate dehydrogenase.
AB  - In recent years, more and more scholars tend to study neuroblastoma (NB) since it
      possesses increasing morbidity, but lack of effective treatment. This paper aims
      to investigate variation and clinical significance of the neuron-specific enolase
      (NSE) and lactic dehydrogenase (LDH) level in serum of children with NB before
      and after Auto Peripheral Blood Stem Cell Transplantation (APBSCT). A total of 90
      children with NB from various hospitals were included in this research, and we
      analyzed the relationship between levels of NSE and LDH and the change of disease
      by comparing the two levels before and after APBSCT treatment. The results
      indicated that the positive rate of NSE in serum was high before treatment, and
      the levels of NSE and LDH were remarkably higher than those when the treatment
      was valid; after comprehensive treatment of chemotherapy, excision and
      radiotherapy, there was a significant difference of NSE and LDH levels in serum
      between children with complete remission (CR) and those with partial remission
      (PR); however, no significant differences of NSE and LDH levels were found among
      children in progressive stage compared to before treatment. It is believed that
      NSE and LDH levels are associated to the recurrence and treatment effect of NB,
      proving that both can reflect tumor load, therefore they can be taken as the
      auxiliary indicators for monitoring curative effects of NB treatment. 

PMID- 25864750
TI  - Observation of the clinical effects of iontophoresis of a chinese drug in the
      treatment of degenerative osteoarthropathy.
AB  - Degenerative osteoarthropathy, a kind of arthrosis induced by various factors,
      mainly affects articular cartilage and causes syndesmophyte formation. Its
      morbidity increases year by year, tending to occur more among young people than
      previously. This paper mainly discusses the clinical effects of iontophoresis of
      the Chinese drug in treating degenerative osteoarthropathy. A total of 296 cases
      of degenerative osteoarthropathy were randomly divided into two groups (of both
      genders): the iontophoresis group: the joint was treated with iontophoresis of
      the Chinese drug and a medium frequency electrotherapy instrument; the frequency
      electrotherapy group: the joint was treated only by medium frequency
      electrotherapy. The two groups were both treated for 30 min once a day, for a
      total of 4 weeks. The results of the study showed that, the total effective rate
      in the medium frequency electrotherapy group was 74.3%, the iontophoresis group
      was 93.2%, indicating the curative effect of iontophoresis of the Chinese
      medicine. The above finding indicates that, iontophoresis has a good clinical
      effect in the treatment of osteoarthropathy and deserves to be promoted and
      applied.

PMID- 25864751
TI  - The expression of p53, mgmt and egfr in brain glioma and clinical significance.
AB  - In order to discuss the expression of P53, MGMT (O6-methylguanine-DNA
      methyltransferase) and EGFR (epidermal growth factor receptor) in brain glioma
      and their clinical significance, this paper collected clinical features of 40
      patients. We observed the expression of P53, MGMT and EGFR in samples using
      immuohisto-chemistry assay and analyzed their interaction, as well as their
      relationship to brain glioma. It was found that among 40 cases of brain glioma
      samples, cases with positive P53 expression accounted for 47.5%, and its
      expression in high-grade brain glioma was higher than in low-grade brain glioma
      (P less than 0.05); cases with positive MGMT expression accounted for 37.5%;, and
      its expression in high-grade glioma and low-grade brain glioma had no statistical
      significance (P>0.05); cases with positive EGFR expression accounted for 55%, and
      its expression in high-grade brain glioma was higher than in low-grade brain
      glioma (P less than 0.05); the expression of P53, MGMT and EGFT were not
      correlated to age, gender or size of tumor; P53 expression was negatively
      correlated to MGMT expression (P < 0.05) but positively correlated to EGFR
      expression (P < 0.05) demonstration that P53, EGFR and MGMT play important roles
      in the occurrence and development of brain glioma.

PMID- 25864752
TI  - Clinical research of persimmon leaf extract and ginkgo biloba extract in the
      treatment of vertebrobasilar insufficiency.
AB  - This paper aims to compare the curative effects of persimmon leaf extract and
      ginkgo biloba extract in the treatment of headache and dizziness caused by
      vertebrobasilar insufficiency. Sixty patients were observed, who underwent
      therapy with persimmon leaf extract and ginkgo biloba extract based on the
      treatment of nimodipine and aspirin. After 30 days, 30 patients treated with
      persimmon leaf extract and 30 patients with ginkgo biloba extract were examined
      for changes in hemodynamic indexes and symptoms, such as headache and dizziness.
      The results showed statistically significant differences of 88.3% for the
      persimmon leaf extract and 73.1% for the ginkgo biloba extract, P < 0.05.
      Compared to the group of ginkgo biloba extract, the group of persimmon leaf
      extract had more apparent improvement in the whole blood viscosity, plasma
      viscosity, fibrinogen, hematokrit, and platelet adhesion rate, and the difference
      was statistically significant (P < 0.05 or P < 0.01). Based on these analyses, it
      can be concluded that persimmon leaf extract is better than ginkgo biloba extract
      in many aspects, such as cerebral circulation improvement, cerebral vascular
      expansion, hypercoagulable state lowering and vertebrobasilar insufficiency
      induced headache and dizziness relief.

PMID- 25864753
TI  - Changes of serum vascular endothelial growth factor of patients with rectal
      cancer before and after neoadjuvant chemotherapy and tumor progress.
AB  - In the rapid development of armamentarium, neoadjuvant chemotherapy has become an
      important part of a multi-instrument comprehensive treatment of malignant tumor,
      which presents promising application prospects. This paper researches changes of
      Vascular Endothelial Growth Factor (VEGF) and Vascular Endothelial Growth Factor
      2 (VEGF-2) in serum of patients with rectal cancer before and after neoadjuvant
      chemotherapy and discusses how tumor progression rules relate to curative effect
      and prognosis. Enzyme linked immunosorbent serologic assay (ELISA) was applied
      for the detection of VEGF expression and VEGF-2 expression of 45 patients with
      rectal cancer (treatment group) before and after neoadjuvant chemotherapy, which
      was compared to the expressions of 45 healthy people (control group). After 8
      weeks of continuous neoadjuvant chemotherapy, the results did not present obvious
      differences of VEGF and VEGF-2 expression in patients with different curative
      effects between pre-chemotherapy and post-chemotherapy. However, VEGF and VEGF-2
      expression of patients with CR+PR and NC significantly decreased. This proved the
      excellent curative effect of neoadjuvant chemotherapy, with which the expressions
      of VEGF and VEGF-2 of rectal cancer patients decreased. The above experiment
      provides new ideas for the application of neoadjuvant chemotherapy in treating
      rectal cancer. 

PMID- 25864754
TI  - Effect of integrin combined laminin on peripheral blood vessel of cerebral
      infarction and endogenous nerve regeneration.
AB  - The third Chinese nationwide survey on causes of death states that
      cerebrovascular disease, accounting for 22.45% of total deaths, ranks as the
      first cause of death among rural and urban residents. It has become a serious
      public health problem since it has the highest disability and fatality rate among
      single diseases. Cerebral infarction is the most common cerebrovascular disease.
      In order to enhance the treatment response of cerebral infarction, this paper
      established male Sprague Dawley (SD) rat reperfusion model with 2 h of cerebral
      artery embolism by suture method. Neurological function deficit was scored
      according to rat improvement 24 h after model establishment, and 50 rats with
      scores between 10 and 13 were included in an ultimate experiment and were
      randomly divided into 5 groups: undisturbed control group, vascular endothelial
      growth factor (VEGF) up-regulated vessel group, endostatin down-regulated vessel
      group, ventricle injected Cxc Chemokin Receptor 4 (CXCR4) antibody group,
      ventricle injected alpha6beta1 antagonist (GoH3 antibody) group, respectively.
      The experiment was initiated after grouping and measurement of the relative data.
      The obtained results showed that the behavioral recovery of the VEGF group was
      more obvious compared with the control group, and the differences were
      statistically significant. The research was carried out using decreased modified
      neurological severity scores (mNSS), and the time a rat took to remove a pasted
      object. However, the behavioral recovery in the endostatin group, anti-CXCR4
      group and GoH3 group was slow, and the difference was statistically significant,
      which showed as slowly decreased mNSS scoring and inconspicuous improved time of
      a rat removing a sticker. Compared with the control group, the number of
      peripheral BrdU+/ vWF+ cells of rat cerebral infarction in the VEGF group
      increased, and the peripheral VEGF expression quantity of cerebral infarction
      increased, thus the difference was statistically significant. However, cells in
      the endostatin group, anti-CXCR4 group, and GoH3 group were fewer and VEGF
      expression was reduced, and the difference was statistically significant. All
      these findings suggest that the promotion of angiogenesis after cerebral
      infarction can better provide the vascular niche for the proliferation, migration
      and differentiation of neural stem/progenitor cells (NSPCs), thereby further
      promoting endogenous nerve regeneration. NSPCs can always closely connect with
      vessels through the interaction of integrin alpha6beta1 and laminin; furthermore,
      under the support provided by the vascular niche and the chemotaxis of stromal
      cellderived factor (SDF-1), NSPCs can migrate from the subventricular zone (SVZ)
      to the periphery of infarction. 

PMID- 25864755
TI  - Expression of pleiotrophin in small cell lung cancer.
AB  - Pleiotrophin (PTN) is a kind of heparin binding growth factor closely related to
      tumor progression. This study aimed to discuss the significance of the expression
      of PTN in benign and malignant lung cancer tissues, especially small cell lung
      cancer. Lung cancer samples were collected for study and lung tissue samples with
      benign lesions were taken as controls. The expression of PTN was detected using
      tissue chip combined with the immunohistochemical method, and the differences of
      small cell lung cancer with non-small cell lung cancer and benign lesion tissue
      were compared. It was found that PTN expression was mainly located in the
      cytoplasm and membrane of cells; PTN expression in the lung cancer group was
      higher than that in the control group (p < 0.01), and PTN expression in the small
      cell cancer group was higher than that in the squamous carcinoma group and
      glandular cancer group (p < 0.05). In addition, PTN expression quantity in
      patients with lung cancer were in close correlation with TNM staging,
      pathological type and tumor differentiation degree (p < 0.05). PTN was found to
      express abnormally high in lung cancer, especially small cell lung cancer tissue.
      PTN is most likely to be a new tumor marker for diagnosis and prognosis of lung
      cancer.

PMID- 25864756
TI  - betaig-h3 CORRELATES WITH RELATED FACTORS OF PERITONEAL METASTASIS OF GASTRIC
      CANCER.
AB  - betaig-h3 is an extracellular matrix protein induced by transforming growth
      factor-beta1 (TGF-beta1) and involved in adhesion between cell and cell, cell and
      matrix. It has been proved that betaig-h3 is highly expressed in human lung
      cancer and colorectal cancer cells, and thus it is considered to have the same
      effect on gastric cancer cells. This research applied histochemical staining and
      RT-PCR to detect the content of betaig-h3 in peritoneal mesothelial cells and the
      content of carcino embryonic antigen (CEA) mRNA in abdominal dropsy or peritoneal
      washing liquid, in order to explore the relationship between the factors of
      peritoneal metastasis of gastric cancer and betaig-h3. It was found that the
      positive ratio of betaig-h3 in the gastric cancer group was higher than that in
      the benign disease group, and the positive rate of immunohistochemistry was
      closely related to the relative factors of peritoneal metastasis such as tumor
      infiltration depth, serosal types, macroscopic peritoneal metastasis, CEA mRNA,
      results of pleural lavage cytology (PLC) examination, etc. Research found that
      betaig-h3 expressed distinctly in gastric cancer peritoneal metastasis,
      therefore, it is useful for monitoring biological behavior of gastric cancer. 

PMID- 25864757
TI  - Meta-analysis on postoperative complications of wristband acupoint pressure
      therapy.
AB  - Through searching database such as MEDLINE, CNKI, etc., this paper assesses the
      effect of wristband acupoint pressure, acting on the neiguan acupoint, to relieve
      postoperative complications of adults (mainly nausea and vomiting) using nine
      randomized controlled trials (RCT) and RevMan5.0. In the experimental group,
      acupoint pressure wristband effectively reduced the incidence rate of
      postoperative vomiting by acting on the neiguan point, compared to the placebo
      control group (RR=0.50, 95% CI: 0.37~0.66, P < 0.01). As to the incidence rate of
      postoperative nausea, there was no statistical significance between the
      experimental group and the placebo control group (RR=0.85, 95% CI: 0.72~1.00, P <
      0.05). It was revealed that the application of acupoint pressure wristband on
      neiguan point in postoperative care could effectively relieve postoperative
      vomiting; while postoperative vomiting was not relieved distinctly. Therefore,
      researchers are required to carry out more reliable RCT test for further study
      and discussion, and nurses can bring in acupoint pressure wristband for
      researches on its effectiveness and adaptability.

PMID- 25864758
TI  - Research on the influence of alpha-GalCer activating experimental autoimmune
      myasthenia gravis mice NKT cells at different times on myasthenia gravis.
AB  - This study aims to observe the effect of natural killer T (NKT) cell activation
      on experimental autoimmune myasthenia gravis (EAMG) model by injecting mice with
      alpha-GalCer in enterocoelia at different times, thus to provide a new therapy
      for EAMG. EAMG animal model of C57BL/6 mice was established and the mice were
      injected with alpha-GalCer irritant in enterocoelia. Valpha14 NKT NKT cells were
      then activated through the transfer of CD1d. This paper discusses the effect of
      NKT cell activation on EAMG at different times by observing the variation of
      weight, clinical performance and relevant immunity indexes of mice. In C57BL/6
      mice, the EAMG incidence rate of the Vehicle Group was 90%, the average onset
      duration was 37 +/- 6 days; The incidence rate of alpha-GalCer prevention group
      was 30%;, the average onset duration was 51 +/- 9 days. The forward immunization
      of alpha-GalCer activates NKT and protects C57BL/6 mice from the occurrence of
      EAMG, which provides basis for prevention and treatment of EAMG and other
      autoimmune diseases.

PMID- 25864759
TI  - Analysis of immunity index and immunopathogenesis pattern of lupus nephritis
      patients.
AB  - Joint detection of anti-dsDNA antibodies, anti-U1RNP, anti-SM antibodies, anti
      SSA antibodies, anti-ribosomal P protein antibodies, anti-nucleosome antivodies
      (Anua), anti-histone antibodies (AHA) and antinuclear antibodies brings to the
      early diagnosis of systemic lupus erythematosus (SLE) and speculation of renal
      lesion degree of lupus nephritis patients in order to choose a specific
      therapeutic schedule. This paper analyzed the abnormal immunology features and
      connections of each pathological pattern of LN renal biopsy and probed into the
      essence in order to provide basis for diagnosis, treatment, pathological pattern
      speculation and forward assessment of LN. We chose 97 cases, treated them with
      renal biopsy and pathological pattern classification, analyzed pathological
      pattern distribution, different pathological patterns and the correlation of
      immunity index with anti-dsDNA antibodies, anti-U1RNP, anti-Sm antibodies, anti
      SSA antibodies, anti-ribosomal P protein antibodies, Anua, AHA and ANA of the
      first renal biopsy were taken as the experiment index. The results showed that
      the morbidity of the male was distinctly lower than the female and the age of
      onset was much lower (P < 0.05); pattern I, pattern II, pattern III, pattern IV,
      pattern V, and pattern VI accounted for 1.0%, 3.1%, 12.4%, 47.4%,16.5%, 15.5%,
      4.1%, 0%,respectively; among all the LN patients, there were respectively 59, 43,
      28, 52, 51, 48, 36 and 93 cases in which anti-dsDNA antibody, anti-U1RNP
      antibody, anti-Sm antibody, anti-SSA antibody, anti-ribosomal P protein
      antibodies, Anua, AHA and ANA had increased and the positive rate was 60.8%,
      44.3%, 28.9%, 53.6%, 52.6%, 49.5%, 37.1% and 95.9%, respectively. In conclusion,
      pattern IV is the most common of all pathological patterns of LN. Among the
      immunity index, anti- U1RNP antibodies and anti-SSA antibodies are positively
      correlated with anti-dsDNA antibodies; Anua is positively correlated with anti
      dsDNA antibodies and AHA; anti-dsDNA antibodies, anti U1RNP antibodies, anti-Sm
      antibodies, anti SSA antibodies, AHA, anti-ribosomal P protein antibodies and ANA
      have no obvious correlation with LN renal lesions degree; Anua level of serum is
      positively correlated with LN renal lesions degree.

PMID- 25864760
TI  - The comparison between vitamin d concentration in upper silesia patients with
      prostate cancer and with benign prostatic hyperplasia.
AB  - A number of studies have shown that vitamin D has a protective effect against the
      development of cancer, which may also be related to prostate cancer. Low serum
      vitamin D concentration has also been demonstrated in benign prostate
      hyperplasia. We compared serum vitamin D concentration in two groups of Polish
      men with prostate cancer and benign prostate hyperplasia. Each group comprised 30
      patients. The concentration was determined by ELISA. To assess the difference
      between the study population, non-parametric Mann Whitney U test was used. The
      results revealed that patients with prostate cancer are deficient in vitamin D
      (median =25.3, quartiles q1 - q3: 13.4 -33.4). The concentration of vitamin D in
      the group of patients with prostate cancer was lower than in the group of benign
      prostatic hyperplasia with vitamin D deficiency (median =34.8, quartiles q1 - q3:
      17.9 ? 44.3). Vitamin D concentration in Polish men with prostate cancer is lower
      compared to patients with benign prostatic hyperplasia. 

PMID- 25864761
TI  - Relationship between adipoq gene polymorphism and lipid levels and diabetes.
AB  - Metabolic syndrome (MS), a series of physiological and metabolic disorders caused
      by insulin resistance, combines clinical syndrome of abdominal obesity, diabetes
      or impaired glucose regulation, dyslipidemia, hypertension and other metabolic
      diseases. Several studies have found that multiple single nucleotide polymorphism
      (SNP) exists in adiponectin gene (ADIPOQ) and some unusual mutations might be
      related to hypoadiponectinemia and MS. This study aims to explore the
      relationship between ADIPOQ gene polymorphism and lipid levels and diabetes. A
      total of 1,049 confirmed MS cases were selected for research. From the
      perspective of potential functional SNPs of ADIPOQ gene, tag SNPs, combined with
      environmental factors, we studied the relationship between ADIPOQ gene
      polymorphism and phenotype (serum adiponectin level) and further analyzed the
      correlation of ADIPOQ gene polymorphism and metabolic syndrome components so as
      to clear the relationship between ADIPOQ gene polymorphism and lipid levels and
      diabetes and at the same time provide a scientific basis for preventing primarily
      MS etiology and screening high-risk groups. 

PMID- 25864762
TI  - Effect of prolonged dual anti-platelet therapy on reducing myocardial infarction
      rate after percutaneous coronary intervention.
AB  - This paper aimed to review the interferential effect of prolonged dual anti
      platelet therapy after Percutaneous Coronary Intervention (PCI), and the
      influence on reducing the myocardial infarction rate. A computer search was
      carried out in the relevant libraries and databases, regarding all the short-term
      (<= 6 months) and long-term (> 6 months) dual anti-platelet therapies, and the
      curative and observational studies on the effects and safety of interventional
      therapy. RevMan5.1 software was used to meta-analyze the standard research. A
      total of 8 papers were finally selected. In the randomized controlled research,
      meta-analysis showed that the myocardial infarction rate of a long-term dual
      antiplatelet treatment group was lower than the short-term treatment group
      [OR=0.74, 95% CI (0.56, 0.98), P < 0.0001]. The meta-analysis of observational
      research showed that the myocardial infarction rate of the long-term treatment
      group was lower than the short-term treatment group [OR=0.7, 95% CI (0.45, 1.08),
      P=0.11]; the incidence rate of late stent thrombosis in the long-term treatment
      group was lower than in the short-term treatment group [OR=0.40, 95% CI (0.15,
      1.07), P=0.07]. It can be concluded that in the long-term group (>6 months) dual
      anti-platelet therapy after PCI can reduce the incidence rate of myocardial
      infarction or death. In addition, long-term treatment can reduce the occurrence
      tendency of late stent thrombosis. Furthermore, in the long-term treatment group,
      serious bleeding events did not increase.

PMID- 25864763
TI  - Cytogenetic genotoxic investigation in peripheral blood lymphocytes of subjects
      with dental composite restorative filling materials.
AB  - Dental composite resins are biomaterials commonly used to aesthetically restore
      the structure and function of teeth impaired by caries, erosion, or fracture.
      Residual monomers released from resin restorations as a result of incomplete
      polymerization processes interact with living oral tissues. The objective of this
      study was to evaluate the genotoxicity of a common dental composite material
      (Enamel Plus-HFO), in subjects with average 13 filled teeth with the same
      material, compared to a control group (subjects having neither amalgam nor
      composite resin fillings). Genotoxicity assessment of composite materials was
      carried out in vitro in human peripheral blood leukocytes using sister-chromatid
      exchange (SCE) and chromosomal aberrations (CA) cytogenetic tests. The results of
      correlation and multiple regression analyses confirmed the absence of a
      relationship between SCE/cell, high frequency of SCE(HFC) or CA frequencies and
      exposure to dental composite materials. These results indicate that composite
      resins used for dental restorations differ extensively in vivo in their cytotoxic
      and genotoxic potential and in their ability to affect chromosomal integrity,
      cell-cycle progression, DNA replication and repair. 

PMID- 25864764
TI  - Atrial natriuretic Peptide expression in human articular cartilage.
AB  - This immunohistochemical study aims to investigate the Atrial natriuretic peptide
      (ANP)-presence and localization in human articular cartilage. Fragments of
      articular cartilage covering the femoral head were removed from patients
      submitted to surgical operation after femoral neck fracture without joint
      disease. The samples were immunostained with anti-ANP antibody. The results
      demonstrate that ANP is present in chondrocytes in all the three zones of the
      articular cartilage. Superficial chondrocytes show strong ANP-immunopositivty.
      The presence of ANP in the articular cartilage suggests that ANP may play a role
      in cartilage metabolism by regulating transport of molecules through the
      different zones of the articular cartilage and in maintenance of its homeostasis;
      probably ANP could be also involved in the regulation of the balance between
      synovial fluid and the other body fluids. 

PMID- 25864765
TI  - Comparison of salivary antioxidant enzyme activity between ex-smokers and
      subjects who had never smoked.
AB  - Smoke contains oxidants such as oxygen-free radicals which are probably the major
      cause of damage to biomolecules. A decrease of salivary antioxidant enzymes was
      detected in habitual smokers. However, the effects of cigarette smoke on salivary
      antioxidant enzymes may persist after withdrawal from smoking. The objective of
      this study was to assess salivary superoxide dismutase (SOD) and glutathione
      peroxidase (GSH-Px) activity in ex-smokers in comparison with that of subjects
      who had never smoked. The test group included 25 ex-smokers (13 males and 12
      females; mean age: 48 +/- 8 years) who had given up smoking for at least one year
      but for no more than 2 years, and a control group consisting of 25 subjects (14
      males and 11 females; mean age: 50 +/- 12 years) who had never smoked. Salivary
      samples were collected and SOD and GSH-Px activity was measured. Student?s t-test
      was used to evaluate differences between groups and significant differences were
      observed for p < 0.05. A significant decrease (p < 0.05) of GSH-Px (14.5 +/- 2)
      was observed in the test group compared to the control group (30 +/- 4). However,
      SOD was very similar in the two groups: 0.9 +/- 0.3 in the test group and 0.8 +/-
      0.3 in the controls and no significant difference was detected (p> 0.05).
      Detoxification of hydrogen peroxide by the GSHPx was altered even after
      withdrawal from smoking, while the production of hydrogen peroxide, that is
      mediated by SOD, was not modified.

PMID- 25864767
TI  - Systemic effects of locally injected platelet rich plasma in a rat model: an
      analysis on muscle and bloodstream.
AB  - Abundant evidence suggests that growth factors, contained in platelets alpha
      granules, may play a key role in the early stages of the muscle healing process
      with particular regard to the inflammatory phase. Although the contents of the
      platelet-rich plasma preparations have been extensively studied, the biological
      mechanisms involved as well as the systemic effects and the related potential
      doping implications of this approach are still largely unknown. The aim of the
      present study was to investigate whether local platelet-rich plasma
      administration may modify the levels of specific cytokines and growth factors
      both in treated muscle and bloodstream in rats. An additional aim was to
      investigate more deeply whether the local platelet-rich plasma administration may
      exert systemic effects by analyzing contralateral lesioned but untreated muscles.
      The results showed that platelet-rich plasma treatment induced a modification of
      certain cytokines and growth factor levels in muscle but not in the bloodstream,
      suggesting that local platelet-rich plasma treatment influenced directly or, more
      plausibly, indirectly the synthesis or recruitment of cytokines and growth
      factors at the site of injury. Moreover, the observed modifications of cytokine
      and growth factor levels in contralateral injured but not treated muscles,
      strongly suggested a systemic effect of locally injected platelet-rich plasma. 

PMID- 25864766
TI  - Western blot expression of 5-lipoxygenase in the brain from striped dolphins
      (stenella coeruleoalba) and bottlenose dolphins (tursiops truncatus) with or
      without encephalitis/meningo-encephalitis of infectious nature.
AB  - Dolphin Morbillivirus (DMV), Toxoplasma gondii and Brucella ceti are pathogens of
      major concern for wild cetaceans. Although a more or less severe
      encephalitis/meningo-encephalitis may occur in striped dolphins (Stenella
      coeruleoalba) and bottlenose dolphins (Tursiops truncatus) infected by the
      aforementioned agents, almost no information is available on the
      neuropathogenesis of brain lesions, including the neuronal and non-neuronal cells
      targeted during infection, along with the mechanisms underlying
      neurodegeneration. We analyzed 5-lipoxygenase (5-LOX) expression in the brain of
      11 striped dolphins and 5 bottlenose dolphins, affected or not by encephalitic
      lesions of various degrees associated with DMV, T. gondii and B. ceti. All the 8
      striped dolphins with encephalitis showed a more consistent 5-LOX expression than
      that observed in the 3 striped dolphins showing no morphologic evidence of brain
      lesions, with the most prominent band intensity being detected in a B. ceti
      infected animal. Similar results were not obtained in T. gondii-infected vs T.
      gondii-uninfected bottlenose dolphins. Overall, the higher 5-LOX expression found
      in the brain of the 8 striped dolphins with infectious neuroinflammation is of
      interest, given that 5-LOX is a putative marker for neurodegeneration in human
      patients and in experimental animal models. Therefore, further investigation on
      this challenging issue is also needed in stranded cetaceans affected by central
      neuropathies. 

PMID- 25864768
TI  - The heme oxygenase/biliverdin reductase system in skin cancers.
AB  - The heme oxygenase/biliverdin reductase (HO/BVR) pathway enhances cell stress
      response by degrading excess heme or producing antioxidant and cytoprotective
      molecules. Recently, members of the HO/BVR system have been proposed as
      biomarkers for the early diagnosis of free radical-related diseases. In this
      study, the presence of both the inducible and constitutive HO isoforms (HO-1 and
      HO-2, respectively) and BVR was evaluated by immunohistochemistry in human skin
      cancer samples. Moderate/strong immunoreactivities against HO-1, HO-2 and BVR
      were detected in 100% of the nodular malignant melanoma samples, whereas in basal
      cell carcinoma specimens these figures were 62%, 88% and 60%, respectively, with
      a faint/moderate degree of expression. Faint/moderate HO-1, HO-2 and BVR
      immunoreactivities were detected in 33%, 66% and 100% of melanocytic nevi
      samples, respectively. In conclusion, HO-1 and HO-2 and BVR were expressed in the
      cytosols of skin cancer cells, whereas perilesional normal epidermis showed only
      faint staining, thus leading to the hypothesis that the HO/BVR system is
      activated in skin cancers. 

PMID- 25864769
TI  - Accuracy and feasibility of high-speed dual fluoroscopy and model-based tracking
      to measure in vivo ankle arthrokinematics.
AB  - The relationship between altered tibiotalar and subtalar kinematics and
      development of ankle osteoarthritis is unknown, as skin marker motion analysis
      cannot measure articulations of each joint independently. Here, we quantified the
      accuracy and demonstrated the feasibility of high-speed dual fluoroscopy (DF) to
      measure and visualize the three-dimensional articulation (i.e., arthrokinematics)
      of the tibiotalar and subtalar joints. Metal beads were implanted in the tibia,
      talus and calcaneus of two cadavers. Three-dimensional surface models of the
      cadaver and volunteer bones were reconstructed from computed tomography images. A
      custom DF system was positioned adjacent to an instrumented treadmill. DF images
      of the cadavers were acquired during maximal rotation about three axes (dorsal
      plantar flexion, inversion-eversion, internal-external rotation) and simulated
      gait (treadmill at 0.5 and 1.0 m/s). Positions of implanted beads were tracked
      using dynamic radiostereometric analysis (DRSA). Bead locations were also
      calculated using model-based markerless tracking (MBT) and compared, along with
      joint angles and translations, to DRSA results. The mean positional difference
      between DRSA and MBT for all frames defined bias; standard deviation of the
      difference defined precision. The volunteer was imaged with DF during treadmill
      gait. From these movements, joint kinematics and tibiotalar and subtalar bone-to
      bone distance were calculated. The mean positional and rotational bias (+/
      standard deviation) of MBT was 0.03+/-0.35 mm and 0.25+/-0.81 degrees ,
      respectively. Mean translational and rotational precision was 0.30+/-0.12 mm and
      0.63+/-0.28 degrees , respectively. With excellent measurement accuracy, DF and
      MBT may elucidate the kinematic pathways responsible for osteoarthritis of the
      tibiotalar and subtalar joints in living subjects.

PMID- 25864770
TI  - Co3O4 nanocrystal ink printed on carbon fiber paper as a large-area electrode for
      electrochemical water splitting.
AB  - A large-area, self-supported Co3O4 nanocrystal/carbon fiber electrode for oxygen
      and hydrogen evolution reaction was fabricated via thermal decomposition of the
      [Co(NH3)n](2+)-oleic acid complex and subsequent spray deposition. Due to the
      exposed active sites and good electrical conductivity, its operate voltage for
      overall water splitting is nearly the same as commercial Pt/C. 

PMID- 25864771
TI  - Patient-centered outcomes comparing digital and conventional implant impression
      procedures: a randomized crossover trial.
AB  - OBJECTIVES: The aim of this randomized controlled trial was to compare patient
      centered outcomes during digital and conventional implant impressions. MATERIAL
      AND METHODS: In a crossover study design, intraoral scanning (IOS) [test] as well
      as classical polyether impressions [control] were both performed on 20 patients
      for single-tooth replacement with implant-supported crowns. The sequential
      distribution of either starting with the test or the control procedure was
      randomly selected. Patients' perception and satisfaction on the level of
      convenience-related factors were assessed with visual analogue scale (VAS)
      questionnaires. In addition, clinical work time was separately recorded for test
      and control procedures. Statistical analyses were performed with Wilcoxon signed
      rank tests and corrected for multiple testing by the method of Holm. RESULTS: On
      VAS ranging from 0 to 100, patients scored a mean convenience level of 78.6 (SD
      +/- 14.0) in favor of IOS compared to conventional impressions with 53.6 (SD +/-
      15.4) [P = 0.0001]. All included patients would prefer the digital workflow if in
      the future they could choose between the two techniques. Secondary, IOS was
      significantly faster with 14.8 min (SD +/- 2.2) compared to the conventional
      approach with 17.9 min (SD +/- 1.1) [P = 0.0001]. CONCLUSION: Based on the
      findings of this investigation, both impression protocols worked successfully for
      all study participants capturing the 3D implant positions. However, the digital
      technique emerges as the most preferred one according to patient-centered
      outcomes and was more time-effective compared to conventional impressions.

PMID- 25864772
TI  - Spinal Cord Stimulation for the Treatment of Neuropathic Pain Associated With
      Leprosy: A Case Report.
AB  - BACKGROUND: Leprosy is a major source of nerve damage and may lead to neuropathic
      pain as well as complex regional pain syndrome (CRPS). Spinal cord stimulation is
      an effective treatment for CRPS, but there are no reports of this treatment in a
      patient with leprosy. CASE PRESENTATION: The patient is a 55-year-old man who
      presented with CRPS in the arms and legs secondary to leprosy that persisted
      despite multidrug therapy, steroid treatment, and intravenous immunoglobulin. His
      pain and opioid use were both decreased with insertion of cervical and thoracic
      spinal cord stimulators. CONCLUSION: Spinal cord stimulation may be a valuable
      intervention for patients with leprosy-induced CRPS.

PMID- 25864773
TI  - Assertive Anger Mediates Effects of Dialectical Behaviour-informed Skills
      Training for Borderline Personality Disorder: A Randomized Controlled Trial.
AB  - Dialectical behaviour therapy (DBT)-informed skills training for borderline
      personality disorder (BPD) aims at the development of specific emotion regulation
      skills in patients, particularly with regard to the regulation of problematic
      anger. While the effects of dialectical behaviour skills training have been
      shown, their processes of change are rarely examined. Neacsiu, Rizvi and Linehan
      (2010) found that patient's self-reported use of emotion regulation skills was a
      mediator of therapeutic change in these treatments; however, they found no effect
      for problematic anger. From an integrative perspective on anger (Pascual-Leone &
      Greenberg, 2007; Pascual-Leone & Paivio, 2013), there are several forms of anger,
      varying in their degree of therapeutic productivity. The present add-on
      randomized controlled trial included n = 41 patients with BPD (n = 21 DBT
      informed skills training versus n = 20 treatment as usual). The first study
      examined the outcome of the DBT-informed skills training encompassing basic
      components of training in mindfulness, distress tolerance, interpersonal
      effectiveness and emotion regulation. Results showed that symptom reduction was
      significantly greater in the DBT-informed skills training, compared with the
      treatment as usual. The second study used process assessment, for which all
      patient completers underwent a 50-min-long psychological interview both early and
      late in treatment, which was rated using the Classification of Affective Meaning
      States. DBT-informed skills training produced increased levels of primary
      'assertive' anger, as compared with the treatment as usual, whereas no effect was
      found for 'rejecting' secondary anger. Most importantly, we showed that changes
      in assertive anger mediated the reported symptom reduction, in particular in
      patient's social roles. We discuss these results in the context of underlying
      mechanisms of change in DBT skills group treatments, in particular towards
      developing more productive forms of anger in this patient population. Copyright
      (c) 2015 John Wiley & Sons, Ltd. KEY PRACTITIONER MESSAGE: A 20-session
      dialectical behaviour therapy (DBT)-informed skills training is a promising
      adjunct intervention for patients with borderline personality disorder, in
      particular for reducing problems related to social role. Increases in assertive
      anger mediate the effects of DBT-informed skills training, whereas rejecting
      anger remains unchanged over the course of treatment. Short-term objectives for
      intervention might involve the specific increase of assertive anger in BPD, by
      using DBT-informed skills training; long-term objectives for intervention might
      involve a specific decrease of rejecting anger in BPD.

PMID- 25864774
TI  - Evaluation of the red cell distribution width as a biomarker of early mortality
      in hepatocellular carcinoma.
AB  - BACKGROUND: The red cell distribution width is a biomarker of early mortality
      across various disease states. AIM: To verify whether it may refine estimates of
      survival in hepatocellular carcinoma. METHODS: The red cell distribution width
      measured at diagnosis was analyzed in relationship to mortality by any cause both
      in a retrospective training cohort (N=208), and in an independent prospectively
      collected validation cohort (N=106) of patients with hepatocellular carcinoma.
      Based on Cox proportional hazards modelling, a prognostic index was validated.
      RESULTS: In the training and the validation cohort, median survival time was
      respectively 1026 and 868 days in patients with red cell distribution width
      <=14.6%, vs. 282 and 340 days in patients with red cell distribution width
      >14.6%; the corresponding hazard ratios were 0.43 (95% CI: 0.31-0.60), p<0.0001
      and 0.28 (95% CI: 0.17-0.47), p<0.0001. At multivariate analysis, the red cell
      distribution width remained an independent predictor of survival (p<0.001) in a
      Cox model including other widely accepted prognostic factors. Applying to the
      validation dataset the prognostic index derived from the training dataset, the
      ability of the model to discriminate the survival probabilities of patients was
      confirmed (Harrell's C=0.769). CONCLUSIONS: The red cell distribution width is a
      novel, reproducible, prospectively validated predictor of survival in patients
      with hepatocellular carcinoma.

PMID- 25864779
TI  - beta-Adrenergic receptor agonist increases voltage-gated Na(+) currents in medial
      prefrontal cortex pyramidal neurons.
AB  - The prefrontal cortex does not function properly in neuropsychiatric diseases and
      during chronic stress. The aim of this study was to test the effects of
      isoproterenol, a beta-adrenergic receptor agonist, on the voltage-dependent fast
      inactivating Na(+) currents in medial prefrontal cortex (mPFC) pyramidal neurons
      obtained from young rats. The recordings were performed in the cell-attached
      configuration. Isoproterenol (2MUM) did not change the peak Na(+) current
      amplitude but shifted the IV curve of the Na(+) currents toward
      hyperpolarization. Pretreatment of the cells with the beta-adrenergic antagonists
      propranolol and metoprolol abolished the effect of isoproterenol on the Na(+)
      currents, suggesting the involvement of beta1-adrenergic receptors. The effect of
      beta-adrenergic receptor stimulation on the sodium currents was dependent on
      kinase A and kinase C; the effect was diminished in the presence of the kinase A
      antagonist H-89 and the kinase C antagonist chelerythrine and abolished when the
      antagonists were coapplied. Moreover, isoproterenol depolarized the membrane
      potential recorded using the perforated-patch method, and this depolarization was
      abolished by cesium ions. Thus, in mPFC pyramidal neurons, stimulation of beta
      adrenergic receptors up-regulates the fast-inactivating voltage-gated Na(+)
      currents evoked by suprathreshold depolarizations. 

PMID- 25864780
TI  - Plasma gelsolin and matrix metalloproteinase 3 as potential biomarkers for
      Alzheimer disease.
AB  - Gelsolin (GSN) levels and matrix metalloproteinase 3 (MMP3) activity have been
      found to be altered in the plasma in patients with Alzheimer disease (AD). The
      aim of this study was to determine whether a combination of these proteins with
      clinical data is specific and sensitive enough for AD diagnosis. In 113 non
      demented controls and 113 patients with probable AD, the plasma GSN levels were
      determined using the enzyme-linked immunosorbent assay (ELISA), and the plasma
      MMP3 activity was determined using casein zymography. Logistic regression and
      receiver operating characteristic (ROC) curve analysis were used to determine the
      diagnostic accuracy of these proteins combined with clinical data. Compared with
      the controls, the AD patients had significantly lower GSN levels and
      significantly higher MMP3 activity. Moreover, both the GSN level and MMP3
      activity were significantly correlated with the MMSE scores. In AD patients, the
      GSN level was negatively correlated with MMP3 activity. ROC curve analysis showed
      that the specificity and sensitivity were 77% and 75.2%, respectively, for the
      combination of the following candidate biomarkers: GSN level/the total amount of
      Abeta42 and Abeta40, plasma MMP3 activity and clinical data. With its relatively
      high sensitivity and specificity, this combined biomarker panel may have
      potential for the screening of AD patients. 

PMID- 25864781
TI  - Melatonin exerts protective effect on N2a cells under hypoxia conditions through
      Zip1/ERK pathway.
AB  - Melatonin plays a neuroprotective role in different CNS injuries. However, the
      molecular mechanisms underlying neuroprotection by melatonin are not well
      understood. Here, we studied the effects of melatonin in hypoxia-induced N2a
      cells and our results demonstrated that melatonin not only reduced the level of
      ROS and MDA, induced the increase of SOD, but also increased the cell
      proliferation and inhibited cell apoptosis in hypoxia-induced N2a cells.
      Moreover, we identified that melatonin can activate the MAPK/ERK pathway via
      upregulating the expression of Zip1. Therefore, this study provides a new
      mechanism of melatonin and need our further study in detail. 

PMID- 25864782
TI  - Risk of malignancy in pulmonary nodules: A validation study of four prediction
      models.
AB  - OBJECTIVES: Clinical prediction models assess the likelihood of malignancy in
      pulmonary nodules detected by computed tomography (CT). This study aimed to
      validate four such models in a UK population of patients with pulmonary nodules.
      Three models used clinical and CT characteristics to predict risk (Mayo Clinic,
      Veterans Association, Brock University) with a fourth model (Herder et al. [4])
      additionally incorporating (18)Fluorine-Fluorodeoxyglucose (FDG) avidity on
      positron emission tomography-computed tomography (PET-CT). MATERIALS AND METHODS:
      The likelihood of malignancy was calculated for patients with pulmonary nodules
      (4-30mm diameter) and data used to calculate the area under the receiver
      operating characteristic curve (AUC) for each model. The models were used in a
      restricted cohort of patients based on each model's exclusion criteria and in the
      total cohort of all patients. RESULTS: Two hundred and forty-four patients were
      studied, of whom 139 underwent FDG PET-CT. Ninety-nine (40.6%) patients were
      subsequently confirmed to have malignant nodules (33.2% primary lung cancer, 7.4%
      metastatic disease). The Mayo and Brock models performed similarly (AUC 0.895 and
      0.902 respectively) and both were significantly better than the Veterans
      Association model (AUC 0.735, p<0.001 and p=0.002 respectively). In patients
      undergoing FDG PET-CT, the Herder model had significantly higher accuracy than
      the other three models (AUC 0.924). When the models were tested on all patients
      in the cohort (i.e. including those outside the original model inclusion
      criteria) AUC values were reduced, yet remained high especially for the Herder
      model (AUC 0.916). For sub-centimetre nodules, AUC values for the Mayo and Brock
      models were 0.788 and 0.852 respectively. CONCLUSIONS: The Mayo and Brock models
      showed good accuracy for determining likelihood of malignancy in nodules detected
      on CT scan. In patients undergoing FDG PET-CT for nodule evaluation, the highest
      accuracy was seen for the model described by Herder et al. incorporating FDG
      avidity.

PMID- 25864783
TI  - Relationship of gambling with tobacco, alcohol, and illicit drug use among
      adolescents in the USA: Review of the literature 2000-2014.
AB  - BACKGROUND AND OBJECTIVES: Adolescence is a time during which not only gambling,
      but also tobacco, alcohol, and illicit drug use, usually begin. The purpose of
      this paper is to provide an updated review of the literature on gambling and its
      associations with tobacco, alcohol, and illicit drug use among US youth. METHODS:
      An electronic literature search of PubMed and PsycInfo was conducted for studies
      since 2000 using the keywords "smoking," "tobacco," "nicotine," "cigarette,"
      "gambling," "adolescence," "adolescent," "alcohol," and "substance use." Ten
      articles with unique adolescent samples were located. Because the articles varied
      in regard to definitions of gambling, tobacco, alcohol, and drug use, we provide
      a qualitative review of included studies. RESULTS: Gambling prevalence rates
      ranged from 44.3% to 68% in national telephone-based surveys, from 24.4% to 86%
      among students in school-based surveys, and from 22.5% to 47.4% in surveys of
      convenience samples. Significant associations were reported between gambling and
      tobacco use (4/7 articles), gambling and alcohol use (7/8 articles), and gambling
      and illicit drug use (7/8 articles). CONCLUSIONS: The wide range in rates of
      gambling and problem gambling may be due in part to differences among the studies
      in participant samples, sampling techniques, assessment time frames, and
      definitions of gambling. Despite methodological differences, most studies showed
      significant associations of gambling with tobacco, alcohol, and other illicit
      drug use. SCIENTIFIC SIGNIFICANCE: As accessibility to gambling increases, more
      research is needed to inform prevention efforts and identify youth at-risk for
      gambling and other high-risk behaviors.

PMID- 25864784
TI  - Major food sources contributing to energy intake--a nationwide survey of
      Brazilians aged 10 years and older.
AB  - Identification of major sources of energy in the diet helps to implement dietary
      recommendations to reduce obesity. To determine the food sources of energy
      consumed by Brazilians, we used the traditional method of ranking energy
      contribution of selected food groups and also compared days with and without
      consumption of specific food groups. Analysis was based on two non-consecutive
      days of dietary record from the Brazilian National Dietary Survey, conducted
      among 34,003 Brazilians (aged 10 years or more), taking into account the complex
      design of the survey. Comparison of days with and without consumption gave more
      consistent results, with sweets and cookies as the most important contributors to
      energy intake, increasing 992 kJ/d (95% CI 883, 1096) for those days when
      consumption of cakes, cookies and desserts was reported compared to days without
      their consumption. Savoury snacks, cheese and sugar-sweetened beverages (SSB)
      also increase energy intake by about 600 kJ. The only group associated with
      decreased energy intake was vegetable (-155 kJ; 95% CI -272, -37). Consumption of
      beans, milk and fruits increased the energy intake by about 210 kJ. In total, the
      mean energy intake of the group was 8000 kJ. Except for the consumption of
      vegetables, all of the other ten food groups analysed were associated with
      increased energy intake. Sweets and cookies may increase the energy intake by 12%
      and SSB by 7%, indicating that these two groups are major targets for improving
      healthy eating by reducing energy intake; whereas vegetable intake is associated
      with the reduction of energy content of the diet.

PMID- 25864785
TI  - gammadelta T cells regulate the expression of cytokines but not the manifestation
      of fungal keratitis.
AB  - As an important immunoregulatory cell type, the role of gammadelta T cells in
      fungal keratitis (FK) is unclear. We observed the distribution of gammadelta T
      cells in infected corneas in vivo by two-photon microscopy. The gammadelta T
      cells were depleted by neutralizing antibodies. The cytokine expression profile
      was obtained by protein arrays to determine the cytokines regulated by gammadelta
      T cells. ICAM-1, MIP-2 and IL-17A were evaluated by ELISA assays to confirm the
      role of gammadelta T cells in FK. We counted the number of neutrophils, evaluated
      the volume of fungal hyphae and analyzed the manifestation of the disease. The
      gammadelta T cells increased significantly at 36 h and 72 h post fungal infection
      (P < 0.05) and migrated from the limbus to the infection site. The neutralizing
      antibodies completely depleted the gammadelta T cells in 24 h. The depletion of
      gammadelta T cells led to up regulation of 25 cytokines and down regulation of 3
      cytokines. ICAM-1, MIP-2 and IL-17A changed significantly because of the
      depletion of gammadelta T cells (P < 0.05). However, the number of neutrophils,
      volume of fungal hyphae and manifestation of the disease was not affected by the
      depletion of gammadelta T cells. Our results demonstrated that gammadelta T cells
      have a role in FK via regulation of some cytokines but did not affect the
      manifestation of this disease, suggesting that gammadelta T cells are not the key
      regulator cells in this disease.

PMID- 25864786
TI  - Comment on aripiprazole-associated hiccups: a case and closer look at the
      association between hiccups and antipsychotics.

PMID- 25864787
TI  - Reply to: comment on: aripiprazole-associated hiccups: a case and closer look at
      the association between hiccups and antipsychotics.

PMID- 25864788
TI  - Compliance with hospital medication management standards for safety and efficacy
      information.

PMID- 25864789
TI  - LCZ696 (angiotensin-neprilysin inhibition): the new kid on the heart failure
      block?
AB  - Angiotensin-converting enzyme inhibitors (ACEIs) have been the cornerstone in
      systolic heart failure (HF) regimens over the past 25 years. Their ability to
      block the renin-angiotensin-aldosterone system and their vasodilatory properties
      has repeatedly been shown to lower morbidity and mortality in patients with HF
      having reduced ejection fractions. In August 2014, the New England Journal of
      Medicine published a large trial studying a novel LCZ696 (angiotensin-neprilysin
      inhibition) agent against enalapril, an ACEI. In the phase III trial, LCZ696
      demonstrated superiority to enalapril in composite death from cardiovascular
      causes and hospitalization for HF. The trial was stopped early due to
      overwhelming benefit of the study agent. This article provides an extensive
      review of the mechanism of action, pharmacokinetic properties, clinical efficacy,
      safety, and tolerability of LCZ696. 

PMID- 25864790
TI  - Students' perception of an integrated approach of teaching entire sequence of
      medicinal chemistry, pharmacology, and pharmacotherapeutics courses in PharmD
      curriculum.
AB  - PURPOSE: To develop an integrated approach of teaching medicinal chemistry,
      pharmacology, and pharmacotherapeutics and to evaluate students' perceptions of
      integration as they progress through the PharmD curriculum. METHODS: Instructors
      from each discipline jointly mapped the course contents and sequenced the course
      delivery based on organ systems/disease states. Medicinal chemistry and
      pharmacology contents were integrated and aligned with respective
      pharmacotherapeutics contents to deliver throughout second and third year of the
      curriculum. In addition to classroom lectures, active learning strategies such as
      recitation, case studies, online-discussion boards, open book quizzes, and
      writing patient progress notes were incorporated to enhance student learning.
      Student learning was assessed by examination scores, patient progress notes, and
      writing assignments. The impact of course integration was evaluated by a Web
      based survey. RESULTS: One hundred and sixty-nine students completed the survey.
      Students exhibited positive attitude toward the integrated approach of teaching
      medicinal chemistry, pharmacology, and therapeutics. The P3 and P4 students
      better appreciated the benefits of integration compared to P2 students (P < .05).
      CONCLUSION: Students perceived the course integration as an effective way of
      learning. This study supports course improvement and the viability of expanding
      the concept of integration to other courses in the curriculum.

PMID- 25864791
TI  - Health information given by travel agencies in Pereira, Colombia.

PMID- 25864792
TI  - Bordetella pertussis infection among international travellers: The need for a
      rigorous implementation of vaccine policies.

PMID- 25864793
TI  - Update on simulation-based surgical training and assessment in ophthalmology: a
      systematic review.
AB  - TOPIC: This study reviews the evidence behind simulation-based surgical training
      of ophthalmologists to determine (1) the validity of the reported models and (2)
      the ability to transfer skills to the operating room. CLINICAL RELEVANCE:
      Simulation-based training is established widely within ophthalmology, although it
      often lacks a scientific basis for implementation. METHODS: We conducted a
      systematic review of trials involving simulation-based training or assessment of
      ophthalmic surgical skills among health professionals. The search included 5
      databases (PubMed, EMBASE, PsycINFO, Cochrane Library, and Web of Science) and
      was completed on March 1, 2014. Overall, the included trials were divided into
      animal, cadaver, inanimate, and virtual-reality models. Risk of bias was assessed
      using the Cochrane Collaboration's tool. Validity evidence was evaluated using a
      modern validity framework (Messick's). RESULTS: We screened 1368 reports for
      eligibility and included 118 trials. The most common surgery simulated was
      cataract surgery. Most validity trials investigated only 1 or 2 of 5 sources of
      validity (87%). Only 2 trials (48 participants) investigated transfer of skills
      to the operating room; 4 trials (65 participants) evaluated the effect of
      simulation-based training on patient-related outcomes. Because of heterogeneity
      of the studies, it was not possible to conduct a quantitative analysis.
      CONCLUSIONS: The methodologic rigor of trials investigating simulation-based
      surgical training in ophthalmology is inadequate. To ensure effective
      implementation of training models, evidence-based knowledge of validity and
      efficacy is needed. We provide a useful tool for implementation and evaluation of
      research in simulation-based training.

PMID- 25864794
TI  - Optical Coherence Tomography of Chorioretinopathy Caused by
      Mucopolysaccharidoses.

PMID- 25864795
TI  - Ophthalmic Features of Children Not Yet Diagnosed with Alstrom Syndrome.

PMID- 25864796
TI  - Identification of sources contributing to PM2.5 and ozone at elevated sites in
      the western U.S. by receptor analysis: Lassen Volcanic National Park, California,
      and Great Basin National Park, Nevada.
AB  - The proposed revision of the United States (US) air quality standard for ozone
      will result in violations in sparsely populated remote rural areas in the Western
      US. Replicating air quality as measured at surface monitoring sites by modeling
      is particularly difficult in this region due to complex terrain, poorly
      represented in regional and global models, and uncertainties in emission rates
      and timing at all scales (locally as well as hundreds to thousands of km upwind).
      As an alternative method, a fully empirical, receptor-based scheme using in situ
      aerosol composition and simple meteorological variables to simulate ozone (O3)
      measurements was tested and found to produce O3 simulation results comparable in
      uncertainty to regional modeling, and supporting trajectory-based identification
      of O3 source regions. This approach was tested using two widely-separated (650
      km) high altitude (approx. 2 km above sea level) monitoring sites, Lassen
      Volcanic National Park, in northern California (LAVO) and Great Basin National
      Park in eastern Nevada (GRBA). Comparing correlations between observed O3 and
      aerosols, and examining back-trajectories associated with peak concentrations for
      the two sites permitted distinguishing among local, distant North American, and
      Asian sources of particulate matter (PM2.5) and O3. This analysis indicates that
      anthropogenic enhancement of O3 at LAVO is primarily due to transport from Asia.
      Asia is also the dominant source of anthropogenic O3 at GRBA in spring, but
      regional North American sources of O3 appear to drive additional ozone peaks in
      late summer and fall at this more interior site.

PMID- 25864797
TI  - When trends intersect: The challenge of protecting freshwater ecosystems under
      multiple land use and hydrological intensification scenarios.
AB  - Intensification of the use of natural resources is a world-wide trend driven by
      the increasing demand for water, food, fibre, minerals and energy. These demands
      are the result of a rising world population, increasing wealth and greater global
      focus on economic growth. Land use intensification, together with climate change,
      is also driving intensification of the global hydrological cycle. Both processes
      will have major socio-economic and ecological implications for global water
      availability. In this paper we focus on the implications of land use
      intensification for the conservation and management of freshwater ecosystems
      using Australia as an example. We consider this in the light of intensification
      of the hydrologic cycle due to climate change, and associated hydrological
      scenarios that include the occurrence of more intense hydrological events
      (extreme storms, larger floods and longer droughts). We highlight the importance
      of managing water quality, the value of providing environmental flows within a
      watershed framework and the critical role that innovative science and adaptive
      management must play in developing proactive and robust responses to
      intensification. We also suggest research priorities to support improved systemic
      governance, including adaptation planning and management to maximise freshwater
      biodiversity outcomes while supporting the socio-economic objectives driving land
      use intensification. Further research priorities include: i) determining the
      relative contributions of surface water and groundwater in supporting freshwater
      ecosystems; ii) identifying and protecting freshwater biodiversity hotspots and
      refugia; iii) improving our capacity to model hydro-ecological relationships and
      predict ecological outcomes from land use intensification and climate change; iv)
      developing an understanding of long term ecosystem behaviour; and v) exploring
      systemic approaches to enhancing governance systems, including planning and
      management systems affecting freshwater outcomes. A major policy challenge will
      be the integration of land and water management, which increasingly are being
      considered within different policy frameworks. 

PMID- 25864798
TI  - Helical alignment inversion of microtubules in accordance with a structural
      change in their lattice.
AB  - Giant helical (oriented chiral nematic) alignments of microtubules of nanometer
      to centimeter lengths are known to form over a temperature gradient during
      anisotropic spiral propagation via tubulin dimer addition in a capillary cell.
      Such helical alignments may be modified by the addition of either paclitaxel or
      dimethyl sulfoxide, which induces a lattice (helical) structural change in the
      microtubule itself. In this study, we found that the lattice structural change of
      microtubules brings about inversion of microtubule alignments in the helical
      ordering. Based on microscopy and scattering data, a mechanism for the helical
      ordering of microtubules is discussed in relation to their lattice (helical)
      structure. 

PMID- 25864799
TI  - Airway extravasation induced by increasing airway temperature in ovalbumin
      sensitized rats.
AB  - This study was carried out to determine whether hyperventilation of humidified
      warm air (HWA) induced airway extravasation in ovalbumin (Ova)-sensitized rats.
      Our results showed: (1) After isocapnic hyperventilation with HWA for 2 min,
      tracheal temperature (Ttr) was increased to 40.3 degrees C, and the Evans blue
      contents in major airways and lung tissue were elevated to 651% and 707%,
      respectively, of that after hyperventilation with humidified room air in Ova
      sensitized rats; this striking effect of HWA was absent in control rats. (2) The
      HWA-induced increase in Evans blue content in sensitized rats was completely
      prevented by a pretreatment with either L-732138, a selective antagonist of
      neurokinin type 1 (NK-1) receptor, or formoterol, a selective agonist of beta2
      adrenoceptor. This study demonstrated that an increase in airway temperature
      induced protein extravasation in the major airways and lung tissue of sensitized
      rats, and an activation of the NK-1 receptor by tachykinins released from
      bronchopulmonary C-fiber nerve endings was primarily responsible.

PMID- 25864800
TI  - Reply to Dr. S.A. Ward: Whipp's law, Comroe's law and generality of the
      optimization model of ventilatory control.

PMID- 25864801
TI  - Effects of lipopolysaccharide-induced inflammation on initial lung fibrosis
      during open-lung mechanical ventilation in rats.
AB  - This study aimed to assess the impact of pulmonary inflammation on early fibrotic
      response in rats challenged with increasing doses of lipopolysaccharide (LPS).
      Twenty-four rats were randomized and infused with three different increasing
      doses of continuous LPS infusion (n=8/group) while being ventilated with low
      tidal volumes and open-lung positive end-expiratory pressure. Another eight
      animals served as uninjured control group. Hemodynamics, gas exchange,
      respiratory system mechanics, lung histology, alpha-smooth muscle actin, plasma
      cytokines, and mRNA expression of cytokines and type I and III procollagen in
      lung tissue were assessed. We found impaired hemodynamics and gas exchange as
      well as higher histological lung injury scores and alpha-smooth muscle actin
      expressions in the medium LPS dose compared to control and the lower LPS dose.
      The highest LPS dose did not cause further aggravation of these findings. In all
      LPS groups type I and III procollagen decreased compared to controls and there
      was a negative correlation between type III procollagen-RNA expression and
      proinflammatory mediators. 

PMID- 25864802
TI  - Successful modulation of murine lupus nephritis with tuftsin-phosphorylcholine.
AB  - In areas where helminths infections are common, autoimmune diseases are rare.
      Treatment with helminths and ova from helminths, improved clinical findings of
      inflammatory bowel disease, multiple-sclerosis and rheumatoid-arthritis. The
      immunomodulatory functions of some helminths were attributed to the
      phosphorylcholine (PC) moiety. We aimed to decipher the tolerogenic potential of
      Tuftsin-PC (TPC) compound in mice genetically prone to develop lupus. Lupus prone
      NZBXW/F1 mice received subcutaneously TPC (5 MUg/1 ml), 3 times a week starting
      at 14 weeks age. Autoantibodies were tested by ELISA, T-regulatory-cells by FACS,
      cytokines profile by RT-PCR and cytokines protein levels by DuoSet ELISA.
      Glomerulonephritis was addressed by detection of proteinuria, and immunoglobulin
      complex deposition in the mesangium of the kidneys of the mice by
      immunofluorescence. Our results show that TPC attenuated the development of
      glomerulonephritis in lupus prone mice, in particular, it ameliorated proteinuria
      (p < 0.02), and reduced immunoglobulin deposition in the kidney mesangium. TPC
      also enhanced the expression of TGFbeta and IL-10 (p < 0.001), and inhibited the
      production of IFNgamma and IL-17 (p < 0.03). TPC Significantly enhanced the
      expansion of CD4+CD25+FOXP3+ T-regulatory cells (Tregs) phenotype in the treated
      mice. These data indicate that TPC hampered lupus development in genetically
      lupus prone mice which was exemplified by moderate glomerulonephritis,
      attenuation of pro-inflammatory cytokines and enhancement of anti-inflammatory
      cytokines expression, as well as Tregs expansion. Our results propose harnessing
      novel natural therapy for lupus patients. 

PMID- 25864803
TI  - An improved technique for cerebrospinal fluid collection of cisterna magna in
      Rhesus monkeys.
AB  - BACKGROUND: Currently-used cerebellomedullary cistern puncture method for
      collecting cerebrospinal fluid (CSF) from monkeys is simple, inexpensive, and
      practical, but with high risk for brainstem injury and CSF blood contamination.
      An improved technique was thus developed and characterized. METHOD: Magnetic
      resonance imaging was used to identify the space and position of the cisterna
      magna in monkeys. Accordingly, a newly defined procedure for needle punctuation
      was tested in comparison with the traditional method. Blood contamination in CSF
      samples and brainstem injury were determined to define the superior of the
      improved method over the transitional method. RESULTS: The cisterna magna in
      monkeys was found to be a "?" shape. The needle was punctured into the cisterna
      magna aiming at the wider superior gap avoided brainstem injury. The improved
      method showed that the rate of blood contamination in the CSF samples was reduced
      from 66.7% to 16.7%, the higher rate of blood contamination was associated with
      higher risk for brainstem injury. COMPARISON WITH EXISTING METHODS: In
      traditional method, the needle is punctured aiming at the inferior gap with high
      density of blood vessels. In improved method, the needle is punctured aiming at
      the superior gap, pointing to the nose root while advancing the needle and
      avoiding injury to blood vessels. CONCLUSIONS: This improved technique not only
      avoids blood contamination of CSF, but also prevents brainstem injury during the
      process of CSF collection. It is recommended for adaptation for CSF collection in
      monkeys.

PMID- 25864804
TI  - FRET based ratiometric Ca(2+) imaging to investigate immune-mediated neuronal and
      axonal damage processes in experimental autoimmune encephalomyelitis.
AB  - BACKGROUND: Irreversible axonal and neuronal damage are the correlate of
      disability in patients suffering from multiple sclerosis (MS). A sustained
      increase of cytoplasmic free [Ca(2+)] is a common upstream event of many neuronal
      and axonal damage processes and could represent an early and potentially
      reversible step. NEW METHOD: We propose a method to specifically analyze the
      neurodegenerative aspects of experimental autoimmune encephalomyelitis by Forster
      Resonance Energy Transfer (FRET) imaging of neuronal and axonal Ca(2+) dynamics
      by two-photon laser scanning microscopy (TPLSM). RESULTS: Using the genetically
      encoded Ca(2+) sensor TN-XXL expressed in neurons and their corresponding axons,
      we confirm the increase of cytoplasmic free [Ca(2+)] in axons and neurons of
      autoimmune inflammatory lesions compared to those in non-inflamed brains. We show
      that these relative [Ca(2+)] increases were associated with immune-neuronal
      interactions. COMPARISON WITH EXISTING METHODS: In contrast to Ca(2+)-sensitive
      dyes the use of a genetically encoded Ca(2+) sensor allows reliable intraaxonal
      free [Ca(2+)] measurements in living anesthetized mice in health and disease.
      This method detects early axonal damage processes in contrast to e.g. cell/axon
      morphology analysis, that rather detects late signs of neurodegeneration.
      CONCLUSIONS: Thus, we describe a method to analyze and monitor early neuronal
      damage processes in the brain in vivo.

PMID- 25864805
TI  - Construct validity and clinical utility of current research criteria of DSM-5
      somatic symptom disorder diagnosis in patients with fibromyalgia syndrome.
AB  - OBJECTIVE: The validity and clinical utility of current research criteria of the
      DSM 5 category somatic symptom disorder (SSD) needs to be tested outside the
      setting of psychiatry. METHODS: Consecutive patients with an established
      diagnosis of fibromyalgia syndrome (FMS) were evaluated by medical examination,
      psychiatric interview and self-report questionnaires in an outpatient pain
      medicine center. The diagnosis of SSD was established using published research
      criteria. The discriminative concurrent criterion validity of SSD was tested by
      comparing FMS-patients with and without SSD as to the amount of impairment and of
      health care seeking. Two clinicians blinded as to the purpose of the study,
      assessed the medical reports of patients after the evaluation for the
      determination of the need for psychotherapy based on the German FMS - guideline
      recommendations (clinical utility). RESULTS: 25.6% of 156 patients met the
      criteria of SSD. Patients meeting SSD criteria scored significantly higher in a
      self-report measure of disability. There were no significant differences in the
      number of patients on sick leave or applying for disability pension and in self
      reported doctor visits and physiotherapy in the previous six months. 95.0% of
      patients with SSD and 71.6% of patients without SSD met the criteria of a current
      anxiety or depressive disorder as assessed by the psychiatric interview. 80.0% of
      patients with SSD and 66.7% of patients without SSD received a recommendation for
      psychotherapy. CONCLUSIONS: The construct validity and clinical utility of
      current research criteria of DSM 5 category SSD were limited in German patients
      with FMS.

PMID- 25864807
TI  - Sensitive and precise HPLC method with back-extraction clean-up step for the
      determination of sildenafil in rat plasma and its application to a
      pharmacokinetic study.
AB  - A sensitive HPLC method was developed and validated for the determination of
      sildenafil concentrations in rat plasma (200 MUL) using a liquid-liquid
      extraction procedure and paroxetine as an internal standard. In order to
      eliminate interferences and improve the peak shape, a back-extraction into an
      acidic solution was utilized. Chromatographic separation was achieved on a
      cyanopropyl bonded-phase column with a mobile phase composed of 50 m m potassium
      dihydrogen phosphate buffer (pH 4.5) and acetonitrile (75:25, v/v), pumped at the
      flow rate of 1 mL/min. A UV detector was set at 230 nm. A calibration curve was
      constructed within a concentration range from 10 to 1500 ng/mL. The limit of
      detection was 5 ng/mL. The inter- and intra-day precisions of the assay were in
      the ranges 2.91-7.33 and 2.61-6.18%, respectively, and the accuracies for inter-
      and intra-day runs were within 0.14-3.92 and 0.44-2.96%, respectively. The
      recovery of sildenafil was 85.22 +/- 4.54%. Tests confirmed the stability of
      sildenafil in plasma during three freeze-thaw cycles and during long-term storage
      at -20 and -80 degrees C for up to 2 months. The proposed method was successfully
      applied to a pharmacokinetic study in rats.

PMID- 25864808
TI  - Freelisting on Costs and Value in Health Care by Pediatric Attending Physicians.
AB  - OBJECTIVE: In preparation for the development of a curriculum on health care
      costs and value for pediatricians, the goal of this study was to assess
      pediatricians' baseline perceptions about the concepts of "cost" and "value" in
      health care, and topics that should be included in a curriculum that teaches
      about costs and value in pediatrics. METHODS: Physicians in the Department of
      Pediatrics at The Children's Hospital of Philadelphia received an online
      freelisting survey asking them to generate lists of words that come to mind when
      thinking about "costs" in health care, "value" in health care, and topics to
      include in a curriculum on costs and value in pediatrics. AnthroPac software
      generated salience scores, indicating the relative importance of each term.
      RESULTS: A total of 207 surveys were completed for a 40% response rate. For the
      "cost" prompt, the most salient responses were "excessive," "waste," and
      "insurance." For the "value" prompt, the most salient responses were "outcomes"
      and "quality." For elements to include in a curriculum, the most salient
      responses were "insurance" and "costs." Analyzing responses based on years in
      practice, percentage clinical time, and division resulted in slightly different
      lists and salience scores. CONCLUSIONS: In this freelisting exercise, there was
      general agreement that health care costs are "excessive," that "outcomes" and
      "quality" are integral to value, and that there is a need for education in these
      areas, especially around "insurance." Differences based on years in practice,
      percentage clinical time, or division can inform the development of targeted
      curricula that consider the needs, knowledge, and interests of these groups.

PMID- 25864806
TI  - Distinct metabolomic signatures are associated with longevity in humans.
AB  - Alterations in metabolism influence lifespan in experimental models, but data in
      humans are lacking. Here we use liquid chromatography/mass spectrometry to
      quantify 217 plasma metabolites and examine their relation to longevity in a
      large cohort of men and women followed for up to 20 years. We find that, higher
      concentrations of the citric acid cycle intermediate, isocitrate, and the bile
      acid, taurocholate, are associated with lower odds of longevity, defined as
      attaining 80 years of age. Higher concentrations of isocitrate, but not
      taurocholate, are also associated with worse cardiovascular health at baseline,
      as well as risk of future cardiovascular disease and death. None of the
      metabolites identified are associated with cancer risk. Our findings suggest that
      some, but not all, metabolic pathways related to human longevity are linked to
      the risk of common causes of death. 

PMID- 25864809
TI  - Assuring Adequate Health Insurance for Children With Special Health Care Needs:
      Progress From 2001 to 2009-2010.
AB  - OBJECTIVE: To report on coverage and adequacy of health insurance for children
      with special health care needs (CSHCN) in 2009-2010 and assess changes since
      2001. METHODS: Data were from the National Survey of Children with Special Health
      Care Needs (NS-CSHCN), a random-digit telephone survey with 40,243 (2009-2010)
      and 38,866 (2001) completed interviews. Consistency and adequacy of insurance was
      measured by: 1) coverage status, 2) gaps in coverage, 3) coverage of needed
      services, 4) reasonableness of uncovered costs, and 5) ability to see needed
      providers, as reported by parents. Bivariate and multivariable analyses were
      conducted to assess factors associated with adequate insurance coverage in 2009
      2010. Unadjusted and adjusted prevalence estimates were examined to identify
      changes in the type of insurance coverage and the proportion of CSHCN with
      adequate coverage by insurance type. RESULTS: The proportion of CSHCN with
      private coverage decreased from 64.7% to 50.7% between 2001 and 2009-2010, while
      public coverage increased from 21.7% to 34.7%; the proportion of CSHCN without
      any insurance declined from 5.2% to 3.5%. The proportion of CSHCN with adequate
      coverage varied over time and by insurance type: among privately covered CSHCN,
      the proportion with adequate coverage declined (62.6% to 59.6%), while among
      publicly covered CSHCN, the proportion with adequate insurance increased (63.0%
      to 70.7%). Publicly insured CSHCN experienced improvements in each of the 3
      adequacy components. CONCLUSIONS: There has been a continued shift from private
      to public coverage, which is more affordable, offers benefits that are more
      likely to meet CSHCN needs, and allowed CSHCN to see necessary providers.

PMID- 25864810
TI  - Is Bax/Bcl-2 ratio considered as a prognostic marker with age and tumor location
      in colorectal cancer?
AB  - BACKGROUND: Bax and Bcl-2 are the major members of Bcl-2 family whose play a key
      role in tumor progression or inhibition of intrinsic apoptotic pathway triggered
      by mitochondrial dysfunction. Therefore, the balance between pro- and anti
      apoptotic members of this family can determine the cellular fate. METHODS: In
      this study, the relative level of mRNA expression of Bax and Bcl-2 genes was
      determined using RNA extraction, cDNA synthesis and RT-qPCR technique from 22
      tumoral tissues and adjacent non-tumoral tissues from adenocarcinoma colorectal
      cancer. RESULTS: The potential prognostic and predictive significance of Bax and
      Bcl-2 gene expression and Bax/Bcl-2 ratio were demonstrated in colorectal cancer.
      The significant correlation between qPCR data and different clinicopathologic
      parameters of colorectal carcinoma, including age, gender, tumor size, tumor
      stage, tumor location, and tumor differentiation was also examined.
      Interestingly, no significant correlation was seen between Bax and Bcl-2
      expressions and clinicopathological parameters of colorectal cancer. However,
      Bax/Bcl-2 ratio was statistically correlated with age and tumor location.
      Patients with age above 50 showed decreased levels of Bax/Bcl-2 ratio. Moreover,
      the Bax/Bcl-2 ratio was significantly lower in tumors resected from colon
      compared to sigmoid colon, rectosigmoid and rectum tumors. CONCLUSION: This study
      indicates a significant correlation between age and tumor location with Bax/Bcl-2
      expression ratio, suggesting predictive value as a potential molecular marker of
      colorectal cancer.

PMID- 25864811
TI  - Comparative assessment of neutrophil gelatinase-associated lipocalin (NGAL) and
      cystatin C as early biomarkers for early detection of renal failure in patients
      with hypertension.
AB  - BACKGROUND: Hypertension is one the most common causes of chronic kidney disease
      (CKD). One of the major concerns in hypertensive patients is early detection of
      renal disorders. In the past, serum creatinine (Scr) concentration was used as a
      marker of kidney function, but it proffers a late reflection of reduced
      glomerular filtration rate. Cystatin C and neutrophil gelatinase-associated
      lipocalin (NGAL) have been recently proven to be useful for quantification of
      CKD. Therefore, we compared the diagnostic value of NGAL with cystatin C and
      creatinine to evaluate kidney function in hypertensive patients. METHODS: In this
      study, 42 hypertensive patients and 30 healthy volunteers were recruited. Serum
      cystatin C (Scys C) and plasma NGAL were measured using ELISA method. Creatinine,
      urea, hemoglobin, fibrinogen, and C-reactive protein were measured according to
      the routine methods. Estimated glomerular filtration rate (eGFR) was considered
      as the gold standard method (cut-off value of < 78 ml/min/1.73 m2. RESULTS: In
      the patient group, plasma NGAL, cystatin C, and creatinine were all significantly
      correlated with eGFR, and plasma NGAL correlated best with eGFR. Receiver
      operating characteristics analysis indicated that plasma NGAL was a better
      indicator than creatinine and cystatin C for predicting a GFR < 78 ml/min/1.73
      m2. The sensitivity and specificity for NGAL were 96% and 100%, for cystatin C
      were 92% and 60% and for creatinine were 76% and 47%, respectively. CONCLUSION:
      Plasma NGAL demonstrated a higher diagnostic value to detect kidney impairment in
      the early stages of CKD as compared to Scys C and Scr in hypertensive patients.

PMID- 25864812
TI  - Evaluation of neurogenic potential of human umbilical cord mesenchymal cells; a
      time- and concentration-dependent manner.
AB  - BACKGROUND: Retinoic acid as one of the most important regulators for cell
      differentiation was examined in this study for differentiation of human umbilical
      mesenchymal cells (hUCM). METHODS: After isolation, hUCM were evaluated for
      mesenchymal stem cell properties by flow cytometry and alkaline phosphatase
      assay. Also, doubling time of the cells and their differentiation potential into
      adipogenic and osteogenic cells were tested. hUCM were then cultured with
      different concentrations of retinoic acid, and on days 1, 7, and 12, the
      percentage of differentiated cells was determined by immunostaining for nestin,
      anti-microtubule associated protein 2 (MAP2), glutamic acid decarboxylase (GAD),
      and gamma-aminobutyric acid (GABA) markers. RESULTS: The isolated cells were
      negative for the hematopoietic markers and positive for the mesenchymal markers.
      They showed the population doubling time 60 +/- 3 hours and differentiated into
      osteogenic and adipogenic cells. A descending trend in nestin and an ascending
      trend in MAP2, GAD, and GABA expression were observed from the first day until
      the last day between different concentrations of retinoic acid. CONCLUSION: hUCM
      cells may have the potential to differentiate into neural cells in the presence
      of different incubation period and concentration of retinoic acid.

PMID- 25864813
TI  - Role of GABAB receptor and L-Arg in GABA-induced vasorelaxation in non-diabetic
      and streptozotocin-induced diabetic rat vessels.
AB  - BACKGROUND: Hypertension is considered an independent risk factor for
      cardiovascular mortality in diabetic patients. The present study was designed to
      determine the role of gamma amino butyric acid B (GABAB) receptor and L-arginine
      (L-Arg) in GABA-induced vasorelaxation in normal and streptozotocin-induced
      diabetic rat vessels. METHODS: Diabetes was induced by a single i.p. injection of
      streptozotocin (STZ, 60 mg/kg). Eight weeks later, superior mesenteric arteries
      of all groups were isolated and perfused according to the McGregor method.
      RESULTS: Baseline perfusion pressure of STZ diabetic rats was significantly
      higher than non-diabetic rats in both intact and denuded endothelium. In the
      presence of faclofen, a selective GABAB receptor blocker, GABA-induced relaxation
      in intact and denuded endothelium mesenteric beds of STZ diabetic rats was
      suppressed, but this response in non-diabetic rats was not suppressed. Our
      results showed that in the presence of L-Arg, a nitric oxide precursor, GABA
      induced vasorelaxation in both diabetic and non-diabetic vessels. CONCLUSION:
      From the results of this study, it may be concluded that the vasorelaxatory
      effect of GABA in diabetic vessel is mediated by the GABAB receptor and nitric
      oxide, but it seems that in non-diabetic vessel GABAB receptor does not play any
      role in GABA-induced vasorelaxation, but nitric oxide induced GABA relaxation in
      non-diabetic vessel.

PMID- 25864814
TI  - Protective effects of restricted diet and antioxidants on testis tissue in rats
      fed with high-fat diet.
AB  - BACKGROUND: A high-fat diet (HFD) promotes the oxidative stress formation, which
      in turn has hazardous effects on reproductive system and fertility. The present
      study examines the potential positive effects of a restricted high-fat diet
      (RHFD) and antioxidants consumption on sperm parameters and testis tissue in
      rats. METHODS: Male rats (n = 48) were divided into four groups (12 in each
      group): control group (Cont), HFD group, RHFD, and RHFD with astaxanthin and
      vitamins E and C group (RHFDA). After 12 weeks, serum analysis and sperm
      parameters study were performed. Sections of fixed testes were stained with
      Hematoxilin and Eosin to study the histological changes. A one-way ANOVA was used
      to compare the data. RESULTS: HFD fed animals presented significant increase in
      weight load and serum low density lipoprotein (LDL-C) levels (P < 0.05). The
      sperm count in RHFD was lower than three other groups (P < 0.05) and sperm
      motility of RHFDA group was significantly higher than HFD and RHFD groups (P <
      0.05). The histological study was showed a significant increase in spermatogonium
      number in RHFDA compared to three other groups (P < 0.05). The number of
      spermatocyte I and spermatid in RHFD was significantly (P < 0.05) lower than Cont
      and HFD groups. CONCLUSION: HFD and obesity can affect sperm parameters and
      spermatogenesis and antioxidants consumption may improve their quality. Although
      the RHFD is a benefit way in weight loss and decrease of LDL-C of serum, but it
      is suggested that is not effective on sperm quality improvement.

PMID- 25864815
TI  - Efficient process development of recombinant human granulocyte colony-stimulating
      factor (rh-GCSF) production in Escherichia coli.
AB  - BACKGROUND: The protein hormone granulocyte colony-stimulating factor (GCSF)
      stimulates the production of white blood cells and plays an important role in
      medical treatment of cancer patients. METHODS: An efficient process was developed
      for heterologous expression of the human GCSF in E. coli BL21 (DE3). The feeding
      rate was adjusted to achieve the maximum attainable specific growth rate under
      critical value. In this method, specific growth rate was maintained at the
      maximum value of 0.55 h-1 at the beginning of feeding to 0.4 h-1 at the induction
      time. Recombinant human GCSF (rh-GCSF) was produced as inclusion body. At first,
      inclusion bodies were released by cell disruption and then washed, solubilized
      and refolded. Finally, the rh-GCSF was purified by cation exchange
      chromatography. RESULTS: Obviouly, higher specific growth rate decreases process
      time and consequently increases productivity. The final concentration of biomass
      and GCSF was achieved 126 g DCW.l-1 and 32.1 g.l-1. Also, the final specific
      yield (YP/X) and total productivity of rh-GCSF were obtained 254 mg.g-1 DCW and
      1.83 g.l-1.h-1, respectively. According to the available data, this is one of the
      highest YP/X and productivity that has been reported for any human protein which
      is expressed in E. coli. Recovery yield of purification process was %40 and
      purity of recombinant protein was over than 99%. The circular dichroism spectra
      of purified rh-GCSF, Neupogen and PD-Grastim showed that all proteins have a
      similar secondary structure. CONCLUSION: Modified exponential feeding strategy
      for fed-batch cultivation of recombinant E. coli, results in minimum fed-batch
      duration and maximum productivity.

PMID- 25864816
TI  - Improvement of tissue survival of skin flaps by 5alpha-reductase inhibitors:
      possible involvement of nitric oxide and inducible nitric oxide synthase.
AB  - BACKGROUND: Skin flap grafting is a popular approach for reconstruction of
      critical skin and underlying soft tissue injuries. In a previous study, we
      demonstrated the beneficial effects of two 5alpha-reductase inhibitors, azelaic
      acid and finasteride, on tissue survival in a rat model of skin flap grafting. In
      the current study, we investigated the involvement of nitric oxide and inducible
      nitric oxide synthase (iNOS) in graft survival mediated by these agents. METHODS:
      A number of 42 male rats were randomly allocated into six groups: 1, normal
      saline topical application; 2, azelaic acid (100 mg/flap); 3, finasteride (1
      mg/flap); 4, injection of L-NG-nitroarginine methyl ester (L-NAME) (i.p., 20
      mg/kg); 5, L-NAME (20 mg/kg, i.p.) + azelaic acid (100 mg/flap, topical); 6, L
      NAME (20 mg/kg, i.p.) + finasteride (1 mg/flap, topical). Tissue survival, level
      of nitric oxide, and iNOS expression in groups were measured. RESULTS: Our data
      revealed that azelaic acid and finasteride significantly increased the expression
      of iNOS protein and nitric oxide (NO) levels in graft tissue (P < 0.05). These
      increases in iNOS expression and NO level were associated with higher survival of
      the graft tissue. CONCLUSION: It appears that alterations of the NO metabolism
      are implicated in the azelaic acid- and finasteride-mediated survival of the skin
      flaps.

PMID- 25864817
TI  - Protective effect of vitamin E against diabetes-induced oxidized LDL and aorta
      cell wall proliferation in rat.
AB  - Hyperlipidemia and oxidized-low-density lipoproteins (Ox-LDL) are important
      independent cardiovascular risk factors that have been shown to stimulate
      vascular smooth muscle cell (VSMC) proliferation. The purpose of the present
      study was to investigate the effect of vitamin E on Ox-LDL, lipid profile, C
      reactive protein (CRP), and VSMC proliferation of rat aorta. METHODS: Male Wistar
      rats (n = 32) were divided into four groups namely: sham (SH), control (C), non
      treated diabetic, and vitamin E-treated diabetic (VETD) groups. Ox-LDL, lipid
      profile, CRP and VSMC proliferation of aorta were measured after 42 days.
      RESULTS: The results revealed that along with a significant increase in VSMC
      proliferation, the amount of CRP, Ox-LDL, and lipid profiles in diabetic rats.
      VSMC proliferation was significantly ameliorated, and elevated CRP, Ox-LDL, and
      lipid profiles were also restored to those of shams in VETD. CONCLUSIONS: These
      findings strongly support the idea that diabetes induces Ox-LDL-mediated
      oxidative stress and VSMC proliferation in aorta of rat and imply that vitamin E
      has a strong protective effect as an antioxidant.

PMID- 25864818
TI  - Treating temporomandibular disorders with permanent mandibular repositioning: is
      it medically necessary?
AB  - In this paper, the authors review the rationale and history of mandibular
      repositioning procedures in relation to temporomandibular disorders (TMDs) as
      these procedures have evolved over time. A large body of clinical research
      evidence shows that most TMDs can and should be managed with conservative
      treatment protocols that do not include any mandibular repositioning procedures.
      Although this provides a strong clinical argument for avoiding such procedures,
      very few reports have discussed the biologic reasons for either accepting or
      rejecting them. This scientific information could provide a basis for determining
      whether mandibular repositioning procedures can be defended as being medically
      necessary. This position paper introduces the biologic concept of homeostasis as
      it applies to this topic. The continuing adaptability of teeth, muscles, and
      temporomandibular joints throughout life is described in terms of homeostasis,
      which leads to the conclusion that each person's current temporomandibular joint
      position is biologically "correct." Therefore, that position does not need to be
      changed as part of a TMD treatment protocol. This means that irreversible TMD
      treatment procedures, such as equilibration, orthodontics, full-mouth
      reconstruction, and orthognathic surgery, cannot be defended as being medically
      necessary. 

PMID- 25864819
TI  - Is it possible to diagnose caries under fixed partial dentures with cone beam
      computed tomography?
AB  - OBJECTIVE: The goal of this study was to determine the possibility of
      detecting/diagnosing caries under fixed partial dentures using cone beam computed
      tomography. STUDY DESIGN: A range of teeth with grade 3 to 6 caries, according to
      International Caries Detection and Assessment System criteria, were selected. All
      teeth were prepared, and three different specimens- zirconia full-ceramic,
      lithium disilicate full-ceramic, and metal-supported ceramic crowns-were built
      for each tooth. Each specimen underwent scanning by cone beam computed
      tomography. Opacity values were recorded and evaluated using two-way analysis of
      variance. The Tukey test was performed for material and slice differences, and
      the t test for mean gray value differences, between caries and noncaries regions
      of each material. RESULTS: Significant differences were detected with respect to
      horizontal location (anterior/posterior), restoration type (crown/bridge),
      material (zirconia/lithium disilicate/metal), and situation (caries/noncaries) (P
      < .001). Mean gray values of caries and noncaries regions were found to differ
      for each material. There were no significant differences with respect to vertical
      position. CONCLUSIONS: Cone beam computed tomography can be used as a
      posttreatment diagnostic technique for detecting caries under high-atomic-number
      fixed plate dentures. By combining high resolution and accuracy, cone beam
      computed tomography could provide the means for diagnosing caries without
      removing fixed plate dentures.

PMID- 25864821
TI  - Researchers should be aware of partial verification bias in diagnostic accuracy
      studies.

PMID- 25864820
TI  - Mandibular inferior cortical bone thickness on panoramic radiographs in patients
      using bisphosphonates.
AB  - OBJECTIVE: The goal of this study was to detect dimensional changes in the
      mandibular cortical bone associated with bisphosphonate (BP) use and to correlate
      measurements of the cortical bone with the cumulative dose of BPs. STUDY DESIGN:
      Mandibular inferior cortical bone thickness (MICBT) was measured under the mental
      foramen on panoramic radiographs of patients with and without bisphosphonate
      related osteonecrosis of the jaws (BRONJ) taking BPs and controls. RESULTS:
      Patients with BRONJ had the highest mean MICBT (6.81 +/- 1.35 mm), compared with
      patients without BRONJ taking BPs (5.44 +/- 1.09 mm) and controls (4.79 +/- 0.85
      mm) (P < .01). Mean MICBT of patients with BRONJ was significantly higher than
      that of patients without BRONJ taking BPs. There was a correlation between MICBT
      and cumulative dose of zolendronate. CONCLUSIONS: Measurement of MICBT on
      panoramic radiographs is a potentially useful tool for the detection of
      dimensional changes associated with BP therapy.

PMID- 25864822
TI  - Insights concerning partial verification bias in retrospective FNAC studies.

PMID- 25864823
TI  - Intradisciplinary approach: the end of a love story.

PMID- 25864824
TI  - Intradisciplinary approach.

PMID- 25864825
TI  - A rare cause of gingival recession: morphea with intra-oral involvement.
AB  - Morphea is an inflammatory disorder of the skin and underlying tissues
      characterized by an overabundance of collagen leading to fibrosis. The prevalence
      of this disease is estimated at around 0.4-2.7/100,000 people. When the process
      occurs in the gingival tissues, it induces traction, which can cause gingival
      recession. A 19-year-old woman was referred to the clinic for a progressive
      recession on teeth 11 and 12. A pale, atrophic, linear region extending from her
      nose to her upper lip on the right-hand side of her face was diagnosed as morphea
      en coup de sabre. Cone beam computed tomography, quantitative polymerase chain
      reaction and histologic evaluation were used to assess the pathology. Treatment
      with methotrexate was conducted. After 12 months, no progression of the recession
      could be observed. 

PMID- 25864826
TI  - [Molecular mechanisms of synapse pathology in ATR-X syndrome].

PMID- 25864827
TI  - [Molecular mechanism in Rett syndrome].

PMID- 25864828
TI  - [Towards elucidating the regulatory roles of CDKL5 in synaptic transmission].

PMID- 25864829
TI  - [Phenotypic analysis of IL1RAPL1 knockout mice].

PMID- 25864830
TI  - [Pathology and treatment of autism spectrum disorders].

PMID- 25864831
TI  - [Organ network for preventing metabolic syndromes with a reference to the roles
      of osteocalcin].

PMID- 25864832
TI  - [Fluorescence-based method to assess the activity of chaperone-mediated
      autophagy].

PMID- 25864833
TI  - [Collaboration between academia for the development of translational research].

PMID- 25864834
TI  - [Gangliosides and nociception].

PMID- 25864835
TI  - [Mas-related G protein-coupled receptors and itch].

PMID- 25864836
TI  - G-quadruplex ligands exhibit differential G-tetrad selectivity.
AB  - A rapid and simple equilibrium-binding assay mediated by ligand-induced
      fluorescence quenching of fluorophore-labelled G-quadruplex (G4) structures
      enabled quantitative interrogation of mutually exclusive ligand binding
      interactions at opposed G-tetrads. This technique revealed that the ligands
      TmPyP4, PhenDC3, and PDS have differential chemotype-specific binding preferences
      for individual G-tetrads of a model genomic G4 structure. 

PMID- 25864838
TI  - pi-Conjugated bis(terpyridine)metal complex molecular wires.
AB  - Bottom-up approaches have gained significant attention recently for the creation
      of nano-sized, ordered functional structures and materials. Stepwise coordination
      techniques, in which ligand molecules and metal sources are reacted
      alternatively, offer several advantages. Coordination bonds are stable,
      reversible, and self-assembling, and the resultant metal complex motifs may
      contain functionalities unique to their own characteristics. This review focuses
      on metal complex wire systems, specifically the bottom-up fabrication of linear
      and branched bis(terpyridine)metal complex wires on electrode surfaces. This
      system possesses distinct and characteristic electronic functionalities, intra
      wire redox conduction and excellent long-range electron transport ability. This
      series of comprehensive studies exploited the customizability of
      bis(terpyridine)metal complex wires, including examining the influence of
      building blocks. In addition, simple yet effective electron transfer models were
      established for redox conduction and long-range electron transport. A fabrication
      technique for an ultra-long bis(terpyridine)metal complex wire is also described,
      along with its properties and functionalities. 

PMID- 25864837
TI  - Exploring origins, invasion history and genetic diversity of Imperata cylindrica
      (L.) P. Beauv. (Cogongrass) in the United States using genotyping by sequencing.
AB  - Imperata cylindrica (Cogongrass, Speargrass) is a diploid C4 grass that is a
      noxious weed in 73 countries and constitutes a significant threat to global
      biodiversity and sustainable agriculture. We used a cost-effective genotyping-by
      sequencing (GBS) approach to identify the reproductive system, genetic diversity
      and geographic origins of invasions in the south-eastern United States. In this
      work, we demonstrated the advantage of employing the closely related, fully
      sequenced crop species Sorghum bicolor (L.) Moench as a proxy reference genome to
      identify a set of 2320 informative single nucleotide and insertion-deletion
      polymorphisms. Genetic analyses identified four clonal lineages of cogongrass and
      one clonal lineage of Imperata brasiliensis Trin. in the United States. Each
      lineage was highly homogeneous, and we found no evidence of hybridization among
      the different lineages, despite geographical overlap. We found evidence that at
      least three of these lineages showed clonal reproduction prior to introduction to
      the United States. These results indicate that cogongrass has limited
      evolutionary potential to adapt to novel environments and further suggest that
      upon arrival to its invaded range, this species did not require local adaptation
      through hybridization/introgression or selection of favourable alleles from a
      broad genetic base. Thus, cogongrass presents a clear case of broad invasive
      success, across a diversity of environments, in a clonal organism with limited
      genetic diversity.

PMID- 25864839
TI  - Solar hydrogen production using carbon quantum dots and a molecular nickel
      catalyst.
AB  - Carbon quantum dots (CQDs) are established as excellent photosensitizers in
      combination with a molecular catalyst for solar light driven hydrogen production
      in aqueous solution. The inexpensive CQDs can be prepared by straightforward
      thermolysis of citric acid in a simple one-pot, multigram synthesis and are
      therefore scalable. The CQDs produced reducing equivalents under solar
      irradiation in a homogeneous photocatalytic system with a Ni-bis(diphosphine)
      catalyst, giving an activity of 398 MUmolH2 (gCQD)(-1) h(-1) and a "per Ni
      catalyst" turnover frequency of 41 h(-1). The CQDs displayed activity in the
      visible region beyond lambda > 455 nm and maintained their full photocatalytic
      activity for at least 1 day under full solar spectrum irradiation. A high quantum
      efficiency of 1.4% was recorded for the noble- and toxic-metal free
      photocatalytic system. Thus, CQDs are shown to be a highly sustainable light
      absorbing material for photocatalytic schemes, which are not limited by cost,
      toxicity, or lack of scalability. The photocatalytic hybrid system was limited by
      the lifetime of the molecular catalyst, and intriguingly, no photocatalytic
      activity was observed using the CQDs and 3d transition metal salts or platinum
      precursors. This observation highlights the advantage of using a molecular
      catalyst over commonly used heterogeneous catalysts in this photocatalytic
      system. 

PMID- 25864841
TI  - Evaluation of the implant-related restorative undergraduate programme at ACTA,
      the Netherlands. Part I: students' satisfaction.
AB  - INTRODUCTION: Due to the increasing use of dental implants, many future dentists
      will encounter implant-related procedures in general practice. Over the past
      decade, implant dentistry is more and more often included in undergraduate
      curricula. Very little is known about students' satisfaction regarding implant
      related undergraduate programmes, as minimal analyses are performed. In
      particular, a lack of information exists regarding programmes where
      undergraduates restore implants. This study describes an evaluation of the
      students' satisfaction regarding the implant-related restorative undergraduate
      programme at ACTA, the Netherlands. MATERIAL AND METHODS: After clinical
      examination and establishment of the treatment plan, undergraduates were required
      to assist postgraduate implantology students during surgery. All patients
      received Straumann (Basel, Switzerland) implants. The restorative phase of the
      treatment was subsequently performed by the undergraduates. A students'
      questionnaire was developed. All questions were exclusively on the restorative
      part of the implant-related programme. RESULTS: In total, 90 patients were
      treated by 78 undergraduates. 146 Straumann implants were restored with 121
      restorations. The most common restoration was a single crown (80.2%), followed by
      three-unit fixed partial dentures (12.4%). The questionnaires showed a high rate
      of students' satisfaction concerning the restorative implant programme. Students
      replied they think they can manufacture an implant-supported crown or FDP without
      supervision after following the programme. In their opinion, the existence of the
      restorative programme should definitely be continued. CONCLUSION: According to
      positive student perceptions, an implant-related restorative programme should be
      recommended for implementation in undergraduate dental curricula. The programme
      at ACTA could be used as a template for other universities.

PMID- 25864842
TI  - A new template to study callosal growth shows specific growth in anterior and
      posterior regions of the corpus callosum in early childhood.
AB  - Most of the studies conducted on the development of the corpus callosum (CC) have
      been limited to a relatively simple assessment of callosal area, providing an
      estimation of the size of the CC in two dimensions rather than its actual
      measurement. The goal of this study was to revisit callosal development in
      childhood and adolescence by using a three-dimensional (3D) magnetic resonance
      imaging template of the CC that considers the horizontal width of the CC and
      compares this with the two-dimensional (2D) callosal area. We mapped callosal
      growth in a large sample of youths followed longitudinally (N = 370 at T1; N =
      304 at T2; and N = 246 at T3). Both techniques were based on a five-section
      subdivision of the CC. The results obtained with the 3D method revealed that the
      rate of CC growth over a 4-year period in the rostrum, the genu, the anterior
      body and the splenium was significantly higher in the youngest age group (< 7
      years) than in older groups, indicating an intense period of development in early
      childhood for the anterior and posterior parts of the CC. Similar results were
      obtained when 2D callosal area was used for the anterior and posterior parts of
      the CC. However, divergent results were found in the mid-body and the caudal body
      of the CC. As shown by differences between 2D estimations and actual 3D
      measurements of callosal growth, our study highlights the importance of
      considering the horizontal width in measuring developmental changes in the CC.

PMID- 25864843
TI  - Regioselective Ring-Opening Polymerization of a Polyhydroxycarboxylic Acid for
      the Synthesis of a Nanoscale Carrier Material with pH-Dependent Stability and
      Sustained Drug Release.
AB  - Synthetic polyesters are usually composed of monohydroxycarboxylic acids to avoid
      the problem of regioselectivity during ring-opening polymerization. In contrast,
      the linear polyester BICpoly contains four secondary OH groups and is
      nevertheless esterified regioselectively at only one of these positions. Neither
      the synthesis of the tricyclic monomers nor the ring-opening polymerization
      requires protecting groups, making BICpoly an attractive novel and biocompatible
      polymer. BICpoly nanoparticles can be loaded with low-molecular weight drugs or
      coated onto surfaces as thin films. The release of loaded compounds makes BICpoly
      an attractive depot for drug release, as shown herein by loading BICpoly with
      dyes or the cytostatic drug doxorubicin. BICpoly is distinguishable from other
      polymers by its characteristic pH-dependent degradation. 

PMID- 25864845
TI  - The developmental profiles of children with idiopathic tonic-clonic epilepsy as
      measured on the Griffiths Mental Development Scales.
AB  - The effect of epilepsy on the development of children with well-controlled tonic
      clonic epilepsy was assessed using the Griffiths Mental Development Scales.
      Twenty-five participants identified as tonic-clonic epilepsy sufferers and twenty
      five participants without epilepsy, matched for age, sex, location and socio
      economic status were tested. Their ages ranged from three to six and a half
      years. There were significant differences between the mean general quotient
      scores and the mean quotient scores on all subscales. The epileptic children
      performed at a significantly lower level than the control group. This was true
      even when the pairs, where the subjects had had status epilepticus, were excluded
      from the analyses. Subjects in the lower socio-economic group performed
      significantly poorer than their peers, which suggests that their social
      environment acts as a further deterrent in optimalising their development. 

PMID- 25864846
TI  - Perceived vulnerability to AIDS among rural Black South African children: a pilot
      study.
AB  - The aim of the study was to examine Black primary school age children's
      perception of vulnerability to AIDS in rural South Africa. Data were collected
      from 100 children chosen by two-stage cluster sampling in a rural community in
      the central region of the Northern Province, in the age range between 6-11 years:
      ages 6-8, 45 (23 boys and 22 girls) and ages 9-11, 55 (24 boys and 31 girls).
      Results indicate that a minority of children (30%) overall felt that anyone can
      get AIDS and that they themselves (17%) can get AIDS. When asked to identify who
      gets AIDS, most children believed that people with specific group membership such
      as sick people, homosexuals or strangers get AIDS, and especially older children
      associated behaviours or actions such as multiple partners or unsafe sex with
      getting AIDS. When the children were asked why they could get AIDS most,
      especially older, children excluded themselves as vulnerable to contracting AIDS
      due to avoiding risky behaviour and group membership. However, some, especially
      younger, children included themselves as vulnerable to contracting AIDS. Fear of
      possibly having AIDS was equally prevalent across the different age groups but it
      was more prevalent in girls than boys, especially in the older age group, yet few
      children in the younger age group thought they had AIDS. Almost a third (30%)
      worried about getting AIDS and even more (40%) thought they will get AIDS. There
      were important age- and gender-related differences regarding vulnerability and
      fears about AIDS, which have relevant implications for AIDS education addressing
      developmentally appropriate concerns. 

PMID- 25864844
TI  - ShenKang injection suppresses kidney fibrosis and oxidative stress via
      transforming growth factor-beta/Smad3 signalling pathway in vivo and in vitro.
AB  - OBJECTIVES: The purpose of this study is to investigate the antifibrosis and
      antioxidation of ShenKang injection (SKI) in vivo and in vitro and to evaluate
      potential mechanisms involved in the treatment of chronic kidney disease (CKD).
      METHODS: In experimental animal studies, CKD was established by 5/6 nephrectomy
      (5/6Nx). Serum creatinine (Scr) and blood urea nitrogen (BUN) were determined.
      Histopathological tests were performed by H&E and Masson trichrome stained. The
      protein expressions of fibronectin (FN), collagen Iota, alpha-smooth muscle actin
      (alpha-SMA) and transforming growth factor-beta (TGF-beta) and phosphorylation of
      Smad3 were measured in 5/6Nx rats. In Human kidney proximal tubular cell line (HK
      2) cells, the effects of TGF-beta/Smad3 signalling pathway on renal fibrosis and
      oxidative injury were examined. KEY FINDINGS: 5/6Nx induced severe renal damages.
      Treatment of rats with SKI markedly reduced levels of Scr and BUN, alleviated
      expression of fibrosis-associated signalling molecules and reduced expression of
      TGF-beta and phosphorylated Smad3. Meanwhile, in HK-2 cells, after exposure to
      TGF-beta and H2 O2 , the protein expression of renal fibrosis was significantly
      increased. The generation of oxidative stress was also elevated. The severity of
      fibrosis and oxidative damage appears to be reduced after treatment with SKI.
      CONCLUSION: SKI inhibits renal fibrosis and oxidative stress through
      downregulation of TGF-beta/Smad3 signalling pathway.

PMID- 25864847
TI  - Reliability of the Beck Depression Inventory and the Self-Rating Anxiety Scale in
      a sample of South African adolescents.
AB  - Objective - This study aimed to assess the reliability of the Beck Depression
      Inventory (BDI) and the Self-Rating Anxiety Scale for epidemiological
      investigations of adolescents' symptoms. Method - Self-report questionnaires were
      administered on two occasions to 104 students in four private high schools in
      Cape Town, South Africa. Test-retest reliability was assessed using Cohen's kappa
      and observed agreement. Internal consistency of each scale was assessed using
      Cronbach's alpha. Resuls - All items of the BDI and all but four of the Self
      Rating Anxiety Scale had at least fair Kappa scores. The remaining four items of
      the Self-Rating Anxiety Scale had reasonable observed agreement and reflect more
      transient states that are likely to change between administrations. Conclusions -
      The results give encouraging indication that these instruments may be reliable in
      developing contexts. However, the study is limited by a sample that is small and
      not sufficiently representative of the broader South African population. Future
      studies should include larger and more representative samples, in order to
      explore item bias in different race and gender subgroups. Validity also needs
      investigation. 

PMID- 25864848
TI  - A young parent's anxieties in raising her infant in a non-traditional family
      structure.
AB  - In this paper I describe a 2-year observation of an infant from a young modern
      family who comes from a more traditional background. I will attempt to indicate
      how the young mother tended to re-enact with her child unresolved conflict
      stemming from her own childhood memories and other experiences in her own
      mothering. These were more pronounced in times of sickness, cultural beliefs,
      rituals and modern versus traditional ways of child rearing. 

PMID- 25864851
TI  - 14(th) Biennial South African Association of Child and Adolescent Psychiatry and
      Allied Professions (SAACAPAP) Conference: Port Elizabeth, South Africa, 1-3
      October 2003.

PMID- 25864849
TI  - The rhythmical dimension of the mother-infant relationship - transcultural
      considerations.
AB  - The paper describes the importance of experiences of shared rhythmicity in the
      mother-infant relationship and their meaning for primary mental development.
      Rhythmical elements are already present throughout prenatal life and research has
      shown responsiveness of the foetus to modifications in the area of auditory
      perception. The author's concept of a prenatal 'sound object', which results from
      the foetus's experience of the maternal voice, includes rhythmical elements.
      Premature birth brings about a disruption of all apsects of prenatal experience
      including rhythmicity. Two infant observations of preterm infants from birth to
      one year of age show how deeply the rhythmical aspects of existence and their
      expression in the primary relationship can be affected, and how these children
      struggle to restore rhythmical aspects of experience. 

PMID- 25864852
TI  - 14(th) Biennial Conference of the South African Association of Child and
      Adolescent Psychiatry and Allied Professions.

PMID- 25864853
TI  - The South African Association for Child and Adolescent Psychiatry and Allied
      Professions (SAACAPAP).

PMID- 25864854
TI  - An Approach to Pain Management in End Stage Renal Disease: Considerations for
      General Management and Intradialytic Symptoms.
AB  - The prevalence and severity of symptoms in patients with advanced chronic kidney
      disease is higher than those of the general population and comparable to those
      with other chronic and serious medical conditions. Despite the prevalence and
      severity in this population, symptoms continue to be under-recognized and
      inadequately managed. The recognition of specific intradialytic pain syndromes
      such as pain related to arteriovenous access, headaches, muscle cramps or
      generalized pain by providers may aid in improving patient compliance and quality
      of life. The approach to pain management in end stage renal disease patients
      follows that of the general population with specific considerations regarding
      clearance and potential side effects guiding selection of agents. Overall,
      evidence is limited regarding the pharmacology of many medications in this
      population. 

PMID- 25864855
TI  - Using water Raman intensities to determine the effective excitation and emission
      path lengths of fluorophotometers for correcting fluorescence inner filter
      effect.
AB  - Fluorescence and Raman inner filter effects (IFE) cause spectral distortion and
      nonlinearity between spectral signal intensity with increasing analyte
      concentration. Convenient and effective correction of fluorescence IFE has been
      an active research goal for decades. Presented herein is the finding that
      fluorescence and Raman IFE can be reliably corrected using the equation
      I(corr)/I(obsd) = 10(dxAx + dmAm) when the effective excitation and emission path
      lengths, dx and dm, of a fluorophotometer are determined by simple linear curve
      fitting of Raman intensities of a series of water Raman reference samples that
      have known degrees of Raman IFEs. The path lengths derived with one set of Raman
      measurements at one specific excitation wavelength are effective for correcting
      fluorescence and Raman IFEs induced by any chromophore or fluorophore, regardless
      of the excitation and emission wavelengths. The IFE-corrected fluorescence
      intensities are linearly correlated to fluorophore concentration over 5 orders of
      magnitude (from 5.9 nM to 0.59 mM) for 2-aminopurine in a 1 cm * 0.17 cm
      fluorescence cuvette. This water Raman-based method is easy to implement. It does
      not involve complicated instrument geometry determination or difficult data
      manipulation. This work should be of broad significance to physical and
      biological sciences given the popularity of fluorescence techniques in analytical
      applications. 

PMID- 25864856
TI  - Histopathological and immunophenotypical criteria for the diagnosis of Sezary
      syndrome in differentiation from other erythrodermic skin diseases: a European
      Organisation for Research and Treatment of Cancer (EORTC) Cutaneous Lymphoma Task
      Force Study of 97 cases.
AB  - BACKGROUND: Patients with erythrodermic disease are a diagnostic challenge
      regarding the clinical and histological differential diagnosis. OBJECTIVES: To
      evaluate histopathological and immunohistochemical diagnostic markers for Sezary
      syndrome. METHODS: Ninety-seven erythrodermic cases [Sezary syndrome (SS), n =
      57; erythrodermic inflammatory dermatoses (EIDs), n = 40] were collected by the
      EORTC Cutaneous Lymphoma Task Force histopathology group. Evaluation criteria
      were (i) epidermal and dermal changes; (ii) morphology of the infiltrate; (iii)
      immunohistochemical analysis of marker loss (CD2, CD3, CD4, CD5 and CD7); (iv)
      bystander infiltrate by staining for CD8, FOXP3 and CD25; and (v) expression of
      Ki-67, CD30, PD-1 and MUM-1. RESULTS: The workshop panel made a correct diagnosis
      of SS in 51% of cases (cutaneous T-cell lymphoma 81%) and of EID in 80% without
      clinical or laboratory data. Histology revealed a significantly increased degree
      of epidermotropism (P < 0.001) and more intraepidermal atypical lymphocytes (P =
      0.0014) in SS biopsies compared with EID. Pautrier microabscesses were seen only
      in SS (23%) and not in EID (P = 0.0012). SS showed significantly more dermal
      cerebriform and blastic lymphocytes than EID. Immunohistochemistry revealed a
      significant loss of CD7 expression (< 50%) in 33 of 51 (65%) cases of SS compared
      with two of 35 (6%) EID (P < 0.001). The lymphocytic infiltrate in SS skin
      samples was found significantly to express PD-1 (P = 0.0053), MUM-1 (P = 0.0017)
      and Ki-67 (P < 0.001), and showed less infiltration of CD8(+) lymphocytes (P <
      0.001). A multivariate analysis identified CD7 loss, increased numbers of small
      cerebriform lymphocytes, low numbers of CD8(+) lymphocytes and increased
      proliferation (Ki-67(+) lymphocytes) as the strongest indicators for the
      diagnosis of SS. CONCLUSIONS: A number of different histological and
      immunophenotypical criteria are required to differentiate between SS and EIDs.

PMID- 25864857
TI  - Mental health in early pregnancy is associated with pregnancy outcome in women
      with pregestational diabetes.
AB  - AIM: To explore the role of early pregnancy health-related quality of life,
      anxiety, depression and locus of control for pregnancy outcome in women with
      pregestational diabetes. METHODS: This was a cohort study of 148 pregnant women
      with pregestational diabetes (118 with Type 1 diabetes and 30 with Type 2
      diabetes), who completed three internationally validated questionnaires: the 36
      item Short-Form Health Survey, the Hospital Anxiety and Depression Scale and the
      Multidimensional Health Locus of Control survey at 8 weeks. Selected pregnancy
      outcomes were preterm delivery (< 37 weeks) and large for gestational age infants
      (birth weight > 90(th) percentile). Differences between groups in the
      questionnaires were analysed using an unpaired t-test. RESULTS: Women with
      preterm deliveries (n = 28) had lower (i.e. worse) mean (sd) quality-of-life
      scores for the two 36-item Short-Form Health Survey scales, Role-Emotional [58.3
      (38.1) vs. 82.9 (31.3); P = 0.0005] and Mental Health [67.7 (20.4) vs. 75.2
      (15.8), P = 0.04], and a lower score for the 36-item Short-Form Health Survey
      scale Mental Component Summary (42.8 (13.1) vs. 48.8 (9.7), P = 0.03) in early
      pregnancy, compared with women with term deliveries. Depression symptoms
      (Hospital Anxiety and Depression Scale depression score >= 8) were more frequent
      in women with preterm vs. term deliveries (seven (25%) vs. six women (5%); P =
      0.003), while levels of anxiety and locus of control were similar in these two
      groups. No difference in early pregnancy scores for health-related quality of
      life, anxiety, depression and locus of control were seen in women delivering
      large or appropriate for gestational age infants. CONCLUSIONS: Poor mental
      quality of life and the presence of depressive symptoms in early pregnancy were
      associated with preterm delivery in women with pregestational diabetes.

PMID- 25864858
TI  - Silica-gold nanoparticles for atheroprotective management of plaques: results of
      the NANOM-FIM trial.
AB  - BACKGROUND: Atheroregression becomes an attractive target for cardiovascular
      treatment. Some clinical trials have demonstrated that intensive therapy with
      rosuvastatin or recombinant ApoA-I Milano can partially reduce the total atheroma
      volume (TAV) up to 6.38 mm(3) or 14.1 mm(3) respectively. Our previous bench
      studies of selected nanotechnologies documented TAV reduction up to an
      unprecedented 79.4 mm(3). METHODS: The completed observational three arms (n =
      180) first-in-man trial (the NANOM FIM trial) assessed (NCT01270139) the safety
      and feasibility of two delivery techniques for nanoparticles (NP), and plasmonic
      photothermal therapy (PPTT). Patients were assigned to receive either (1) nano
      intervention with delivery of silica-gold NP in a bioengineered on-artery patch
      (n = 60), or (2) nano-intervention with delivery of silica-gold iron-bearing NP
      with targeted micro-bubbles and stem cells using a magnetic navigation system (n
      = 60) versus (3) stent implantation (n = 60). The primary outcome was TAV at 12
      months. RESULTS: The mean TAV reduction at 12 months in the Nano group was 60.3
      mm(3) (SD 39.5; min 41.9 mm(3), max 94.2 mm(3); p < 0.05) up to mean 37.8% (95%
      CI: 31.1%, 51.7%; p < 0.05) plaque burden. The analysis of the event free
      survival of the ongoing clinical follow-up shows the significantly lower risk of
      cardiovascular death in the Nano group when compared with others (91.7% vs. 81.7%
      and 80% respectively; p < 0.05) with no cases of the target lesion-related
      complications. CONCLUSIONS: PPTT using silica-gold NP associated with significant
      regression of coronary atherosclerosis.

PMID- 25864859
TI  - EADV Taskforce's recommendations on measurement of health-related quality of life
      in paediatric dermatology.
AB  - The impact of skin conditions in children can profoundly affect a variety of
      lifestyle parameters that may have important personal consequences. Several
      national guidelines for children with different skin conditions recommend health
      related quality of life (HRQoL) measurement as part of the assessment process.
      HRQoL also plays an important role in educational programmes for children with
      chronic skin conditions and their parents. In this paper, the EADV Taskforce on
      Quality of life provides researchers and clinicians data on the achievements in
      this field, as well as the peculiarities of HRQoL assessment in children, and an
      overview of the most commonly used and validated generic, dermatology-specific
      and disease-specific instruments related to paediatric dermatology. Finally, an
      analysis of the current problems of HRQoL assessment in children with skin
      diseases and directions for future studies are also discussed. The main goal of
      this paper is to help dermatologists decide which HRQoL instrument to use with
      children, depending on the context. 

PMID- 25864860
TI  - Lubricin in human achilles tendon: The evidence of intratendinous sliding motion
      and shear force in achilles tendon.
AB  - Achilles tendon is one of the most commonly injured tendons. Mechanical force is
      regarded as a major causative factor. However, the biomechanics of Achilles
      tendon and mechanical mechanism of the injuries are unclear. Lubricin expresses
      at regions exposed to sliding motion and shear force in a number of tissues. This
      study investigated the distribution and concentration of lubricin in human
      Achilles tendons for better understanding the biomechanics of Achilles tendon.
      Achilles tendons were harvested from nine cadavers. Lubricin was extracted from
      various locations proximal to the calcaneal insertion and quantified with ELISA.
      The distribution of lubricin was investigated with immunohistochemistry. Lubricin
      was mainly identified at the interfaces of tendon fascicles, especially in the
      mid-portion of the tendon. The concentration of lubricin in Achilles tendons
      varied by individual and the distance from its calcaneal insertion. The distal
      portion of the tendon had a higher concentration of lubricin than the proximal
      regions of the tendon. This study suggests the presence of intratendinous sliding
      motion of fascicles and shear force at interfaces of fascicles in human Achilles
      tendon. Shear force could be an important mechanical factor for the development
      of Achilles tendinopathy and rupture.

PMID- 25864861
TI  - Sub-Saharan African University Students' Beliefs about Abstinence, Condom Use,
      and Limiting the Number of Sexual Partners.
AB  - Given the high risk of HIV infection among university students in sub-Saharan
      Africa, there is a need for culturally appropriate risk-reduction interventions
      specifically targeting this population. Efforts to reduce the risk require an
      understanding of the modifiable antecedents of sexual-risk behaviors. We report
      the results of a semi-structured elicitation survey based on the reasoned action
      approach to identify behavioral, normative, and control beliefs regarding
      abstinence, condom use, and limiting sexual partners. Two coders classified into
      64 belief categories the written responses of 96 sub-Saharan African university
      students. Most students believed each behavior could reduce risk of HIV
      infection. The students reported that peer pressure and being in a risky
      environment made it harder to practice abstinence. Good communication made it
      easier to use condoms and to limit partners; however, unstable relationships made
      practicing these protective behaviors harder. The identified beliefs help to
      inform the development of theory-based HIV risk-reduction interventions.

PMID- 25864862
TI  - Determination of three estrogens and bisphenol A by functional ionic liquid
      dispersive liquid-phase microextraction coupled with ultra-high performance
      liquid chromatography and ultraviolet detection.
AB  - A hydroxyl-functionalized ionic liquid, 1-hydroxyethyl-3-methylimidazolium
      bis(trifluoromethanesulfonyl)imide, was employed in an improved dispersive liquid
      phase microextraction method coupled with ultra high performance liquid
      chromatography for the enrichment and determination of three estrogens and
      bisphenol A in environmental water samples. The introduced hydroxyl group acted
      as the H-bond acceptor that dispersed the ionic liquid effectively in the aqueous
      phase without dispersive solvent or external force. Fourier transform infrared
      spectroscopy indicated that the hydroxyl group of the cation of the ionic liquid
      enhanced the combination of extractant and analytes through the formation of
      hydrogen bonds. The improvement of the extraction efficiency compared with that
      with the use of alkyl ionic liquid was proved by a comparison study. The main
      parameters including volume of extractant, temperature, pH, and extraction time
      were investigated. The calibration curves were linear in the range of 5.0-1000
      MUg/L for estrone, estradiol, and bisphenol A, and 10.0-1000 MUg/L for estriol.
      The detection limits were in the range of 1.7-3.4 MUg/L. The extraction
      efficiency was evaluated by enrichment factor that were between 85 and 129. The
      proposed method was proved to be simple, low cost, and environmentally friendly
      for the determination of the four endocrine disruptors in environmental water
      samples. 

PMID- 25864863
TI  - Lymphoma in acquired generalized lipodystrophy.
AB  - Acquired generalized lipodystrophy (AGL) is a rare disease thought to result from
      autoimmune destruction of adipose tissue. Peripheral T-cell lymphoma (PTCL) has
      been reported in two AGL patients. We report five additional cases of lymphoma in
      AGL, and analyze the role of underlying autoimmunity and recombinant human leptin
      (metreleptin) replacement in lymphoma development. Three patients developed
      lymphoma during metreleptin treatment (two PTCL and one ALK-positive anaplastic
      large cell lymphoma), and two developed lymphomas (mycosis fungoides and Burkitt
      lymphoma) without metreleptin. AGL is associated with high risk for lymphoma,
      especially PTCL. Autoimmunity likely contributes to this risk. Lymphoma developed
      with or without metreleptin, suggesting metreleptin does not directly cause
      lymphoma development; a theoretical role of metreleptin in lymphoma progression
      remains possible. For most patients with AGL and severe metabolic complications,
      the proven benefits of metreleptin on metabolic disease will likely outweigh
      theoretical risks of metreleptin in lymphoma development or progression. 

PMID- 25864864
TI  - Antioxidant, antibacterial, and anti-inflammatory activities of standardized
      brazilin-rich Caesalpinia sappan extract.
AB  - CONTEXT: Brazilin is a major active principle of Caesalpinia sappan L.
      (Leguminosae or Fabaceae). For industry aspects, brazilin-rich extract (BRE) has
      been prepared and standardized to contain 39% w/w brazilin. BRE may have more
      advantages than brazilin in term of a lower-cost production process. OBJECTIVES:
      To investigate the antioxidant, antibacterial, and anti-inflammatory activities
      of BRE. MATERIAL AND METHODS: BRE was prepared by a simple one-step purification
      of the crude ethanol extract of C. sappan heartwood (CSE) using a Diaion(r) HP-20
      column. The antioxidant activities were determined using three methods, including
      DPPH radical scavenging, reducing power, and beta-carotene bleaching assays, at
      concentration ranges of 1-10, 10-100, and 10-100 ug/mL, respectively. Minimum
      inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of
      BRE (15.6-1000 ug/mL) against Gram-positive and Gram-negative bacteria were
      determined by the broth microdilution method. Anti-inflammatory activity of BRE
      (0.1-5 ug/mL) was evaluated as anti-denaturation activity using bovine serum
      albumin as a substrate. RESULTS AND DISCUSSION: On the basis of beta-carotene
      bleaching assay, BRE showed antioxidant activity with an EC50 value of 60.5
      ug/mL, which was almost equal to that of pure brazilin (52.1 ug/mL). Gram
      positive bacteria were more sensitive to all tested samples than Gram-negative
      bacteria. BRE possessed higher antibacterial activities than CSE, but lower than
      brazilin. MIC/MBC values of 62.5-125/125 and 250-500/250-500 ug/mL were obtained
      for BRE against Gram-positive and Gram-negative bacteria, respectively. A low
      concentration (0.1 ug/mL) of brazilin, BRE, and CSE showed anti-inflammatory
      activity by inhibiting protein denaturation up to 46.8, 54.1, and 61.9%,
      respectively.

PMID- 25864865
TI  - Cardio-oncology Part II: the monitoring, prevention, detection and treatment of
      chemotherapeutic cardiac toxicity.
AB  - Cancer treatment has advanced in recent years with new drugs, complex regimes and
      multiple modalities of treatment; which has improved survival of cancer patients.
      Cardiotoxicity from chemotherapy is an emerging, important issue. Currently,
      echocardiographic evaluation of ejection fraction is the most commonly employed
      diagnostic tool for detecting chemotherapy-induced cardiotoxicity. However, novel
      echocardiographic techniques assessing myocardial mechanics using strain imaging
      can detect earlier changes. New imaging techniques and biomarkers can risk
      stratify patients to identify those requiring closer monitoring. Cardiologists
      collaborating with oncologists can detect and treat cardiovascular
      chemotherapeutic complications earlier, reducing morbidity and mortality. While
      cardiac MRI and multigated acquisition nuclear scanning are alternatives,
      echocardiography has become the mainstream for assessing cardiac function due to
      its portability, efficiency and low cost. Current recommendations regarding
      cardiac monitoring of cancer patients are based on expert consensus opinion.
      There is a need for prospective controlled trials to support specific guidelines.

PMID- 25864866
TI  - Clustered nuclei splitting via curvature information and gray-scale distance
      transform.
AB  - Clusters or clumps of cells or nuclei are frequently observed in two dimensional
      images of thick tissue sections. Correct and accurate segmentation of overlapping
      cells and nuclei is important for many biological and biomedical applications.
      Many existing algorithms split clumps through the binarization of the input
      images; therefore, the intensity information of the original image is lost during
      this process. In this paper, we present a curvature information, gray scale
      distance transform, and shortest path splitting line-based algorithm which can
      make full use of the concavity and image intensity information to find out
      markers, each of which represents an individual object, and detect accurate
      splitting lines between objects using shortest path and junction adjustment. The
      proposed algorithm is tested on both synthetic and real nuclei images. Experiment
      results show that the performance of the proposed method is better than that of
      marker-controlled watershed method and ellipse fitting method. 

PMID- 25864867
TI  - Drift during overground locomotion in newly hatched chicks varies with light
      exposure during embryogenesis.
AB  - In an earlier study of newly hatched chicks we reported that continuous bright
      light exposure throughout incubation accelerated locomotor development and
      continuous dark exposure delayed it, compared to less intense, intermittent light
      exposure. Commonly studied gait parameters indicated locomotor skill was similar
      across groups. However, dark incubated chicks walked with a greater step width,
      raising the possibility of differences in dynamic balance and control of forward
      progression. In this study, we established methods to retrospectively examine the
      previously published locomotor data for differences in lateral drift. We
      hypothesized that chicks incubated in darkness would exhibit more drift than
      chicks incubated in light. Analyses identified differences in forward progression
      between chicks incubated in the two extreme light conditions, supporting the
      study's hypothesis. We discuss the significance of our findings and potential
      design considerations for future studies of light-accelerated motor development
      in precocial and nonprecocial animals.

PMID- 25864868
TI  - Exuberant granulation tissue response associated with Neobenedenia sp.
      (Monogenea: Capsalidae) infestation in two cobia, Rachycentron canadum
      (Linnaeus).
AB  - Monogenean parasite infestations are common in captive marine teleosts, and are
      generally found on the skin and gills. This report describes an unusual
      pathological presentation of exuberant granulation tissue of the gills, suspected
      to be related to Neobenedenia infestation in two cobia housed together at a North
      Carolina aquarium. 

PMID- 25864869
TI  - Direct Staudinger-Phosphonite Reaction Provides Methylphosphonamidates as
      Inhibitors of CE4 De-N-acetylases.
AB  - De-N-acetylases of beta-(1->6)-D-N-acetylglucosamine polymers (PNAG) and beta-(1
      >4)-D-N-acetylglucosamine residues in peptidoglycan are attractive targets for
      antimicrobial agents. PNAG de-N-acetylases are necessary for biofilm formation in
      numerous pathogenic bacteria. Peptidoglycan de-N-acetylation facilitates
      bacterial evasion of innate immune defenses. To target these enzymes, transition
      state analogue inhibitors containing a methylphosphonamidate have been
      synthesized through a direct Staudinger-phosphonite reaction. The inhibitors were
      tested on purified PgaB, a PNAG de-N-acetylase from Escherichia coli, and PgdA, a
      peptidoglycan de-N-acetylase from Streptococcus pneumonia. Herein, we describe
      the most potent inhibitor of peptidoglycan de-N-acetylases reported to date (Ki
      =80 MUM). The minimal inhibition of PgaB observed provides insight into key
      structural and functional differences in these enzymes that will need to be
      considered during the development of future inhibitors. 

PMID- 25864870
TI  - Vitamin D and omega-3 polyunsaturated fatty acid supplementation in athletes with
      exercise-induced bronchoconstriction: a pilot study.
AB  - OBJECTIVE: The aim of this pilot study was to determine the combined effect of
      vitamin D and omega-3 polyunsaturated fatty acid (PUFA) supplementation on airway
      function and inflammation in recreational athletes with exercise-induced
      bronchoconstriction (EIB). METHODS: Ten recreational athletes with EIB
      participated in a single-blind, placebo-controlled trial over six consecutive
      weeks. All subjects attended the laboratory on three occasions. Each visit was
      separated by a period of 3 weeks: visit 1 (usual diet), visit 2 (placebo) and
      visit 3 (SMARTFISH(r) NutriFriend 2000; 30 ug vitamin D3-3000 mg eicosapentaenoic
      acid, 3000 mg docosahexaenoic acid) consumed once daily for a period of 3 weeks.
      Venous blood was collected at the beginning of each trial to determine vitamin D
      status. Spirometry was performed pre- and post-eucapnic voluntary hyperpnoea
      (EVH). RESULTS: The Maximum fall in FEV1 (DeltaFEV1max) post-EVH was not
      different between visits (usual diet: -15.9 +/- 3.6%, placebo: -16.1 +/- 6.1%,
      vitamin D + omega-3 PUFA: -17.8 +/- 7.2%). Serum vitamin D remained unchanged
      between visits. CONCLUSION: Vitamin D and omega-3 PUFA supplementation does not
      attenuate the reduction in lung function post-EVH. This finding should be viewed
      as preliminary until the results of randomised controlled trials are made
      available.

PMID- 25864871
TI  - What distinguishes weight loss maintainers of the German Weight Control Registry
      from the general population?
AB  - OBJECTIVE: Differences between successful long-term weight loss maintainers and
      the general population with regard to eating and weighing habits, non-normative
      eating behaviors, and eating-related and general psychopathological parameters
      are unknown. METHODS: Self-identified weight loss maintainers from the German
      Weight Control Registry (GWCR, n = 494) were compared with a representative
      sample of the general German population (n = 2,129). The samples did not differ
      in current BMI. Using the same assessment instruments in both cohorts, a variety
      of eating-related and psychological variables were determined. RESULTS: The GWCR
      participants reported more self-weighing and higher eating frequency but less hot
      meal consumption and more eating-out-of-home. Binge eating, compensatory
      behaviors, and concerns about shape and weight were reported more often by
      successful weight loss maintainers. Scores of depression and worrying about
      health were slightly higher whereas severity of somatic symptoms was less
      pronounced in the GWCR participants. CONCLUSIONS: Overall, our data suggest that
      successful weight loss maintainers are characterized by more concerns about shape
      and weight, greater binge eating frequency, and higher use of compensatory
      behaviors. The latter suggests that weight loss maintenance might not only be
      achieved by healthy strategies but also by non-normative behaviors which might
      increase the vulnerability for weight regain.

PMID- 25864872
TI  - Description and evaluation of an intraoral cervical plexus anesthetic technique.
AB  - Unsuccessful anesthesia of the inferior alveolar nerve (IAN) may be due to
      supplementary innervations of mandibular molars from other branches, namely the
      cervical plexus (CP). The purpose of this prospective, randomized, double-blind,
      controlled trial was to determine the effectiveness of an intraoral cervical
      plexus anesthetic technique (ICPAT) in mandibular molars with symptomatic
      irreversible pulpitis (SIR) when the IAN and lingual nerve (LN) blocks failed,
      and to provide a description of the technique. Forty patients diagnosed with SIR
      received IAN and LN block anesthesia prior to treatment. After clinical signs of
      anesthesia, patients were subjected to an electrical pulp test (EPT) at 2-min
      cycles for 10 min post-injection. The anesthesia was considered unsuccessful if
      there was a positive EPT response ten minutes following profound lip numbness.
      The experimental group (n = 20) were administered 2% Lidocaine with 1:100,000
      epinephrine using the ICPAT. The control group (n = 20) were administered 0.9%
      sterile saline using the ICPAT. Success was defined as no response on two
      consecutive readings from an EPT. In the experimental group, 60% of subjects
      showed successful anesthesia, whereas none of the subjects in the control group
      had successful anesthesia. A multiple logistic regression analysis showed that
      the anesthesia success rate using the ICPAT method was significantly higher (P <
      0.05) than in the control group, irrespective of molar tooth type. The ICPAT
      method may be useful as a supplementary anesthetic technique for mandibular
      molars with SIR in subjects whom the IAN and LN blocks do not provide adequate
      anesthesia.

PMID- 25864873
TI  - Systematic review with network meta-analysis: comparative efficacy and safety of
      budesonide and mesalazine (mesalamine) for Crohn's disease.
AB  - BACKGROUND: Budesonide and mesalazine (mesalamine) are commonly used in the
      medical management of patients with mild to moderate Crohn's disease. AIM: To
      assess their comparative efficacy and harm using the methodology of network meta
      analysis. METHODS: A comprehensive search of Medline, Embase, the Cochrane
      Library and ClinicalTrials.gov, through October 2014, was performed to identify
      randomised controlled trials (RCTs) that recruited adult patients with active or
      quiescent Crohn's disease, and compared budesonide or mesalazine with placebo, or
      against each other, or different dosing strategies of one drug. RESULTS: Twenty
      five RCTs were combined using Bayesian network meta-analysis. Budesonide 9
      mg/day, or at higher doses (15 or 18 mg/day), was shown superior to placebo for
      induction of remission [odds ratio (OR), 2.93; 95% credible interval (CrI), 1.52
      5.39, and OR, 3.28; CrI, 1.46-7.55 respectively] and ranks at the top of the
      hierarchy of the competing treatments. For maintenance of remission, budesonide 6
      mg/day demonstrated superiority over placebo (OR, 1.69; CrI, 1.05-2.75), being
      also at the best ranking position among all compared treatment strategies. No
      other comparisons (i.e. different doses of mesalazine vs. placebo or budesonide,
      for induction or maintenance of remission) reached significance. The occurrence
      of withdrawals due to adverse events was not shown different between budesonide,
      mesalazine and placebo, in both the induction and maintenance phases.
      CONCLUSIONS: Budesonide, at the doses of 9 mg/day, or higher, for induction of
      remission in active mild or moderate Crohn's disease, and at 6 mg/day for
      maintenance of remission, appears to be the best treatment choice.

PMID- 25864874
TI  - Capturing complexity in work disability research: application of system dynamics
      modeling methodology.
AB  - BACKGROUND: Work disability (WD) is characterized by variable and occasionally
      undesirable outcomes. The underlying determinants of WD outcomes include patterns
      of dynamic relationships among health, personal, organizational and regulatory
      factors that have been challenging to characterize, and inadequately represented
      by contemporary WD models. METHOD: System dynamics modeling (SDM) methodology
      applies a sociotechnical systems thinking lens to view WD systems as comprising a
      range of influential factors linked by feedback relationships. SDM can
      potentially overcome limitations in contemporary WD models by uncovering causal
      feedback relationships, and conceptualizing dynamic system behaviors. It employs
      a collaborative and stakeholder-based model building methodology to create a
      visual depiction of the system as a whole. SDM can also enable researchers to run
      dynamic simulations to provide evidence of anticipated or unanticipated outcomes
      that could result from policy and programmatic intervention. DISCUSSION: SDM may
      advance rehabilitation research by providing greater insights into the structure
      and dynamics of WD systems while helping to understand inherent complexity.
      Challenges related to data availability, determining validity, and the extensive
      time and technical skill requirements for model building may limit SDM's use in
      the field and should be considered. IMPLICATIONS FOR REHABILITATION: Contemporary
      work disability (WD) models provide limited insight into complexity associated
      with WD processes. System dynamics modeling (SDM) has the potential to capture
      complexity through a stakeholder-based approach that generates a simulation model
      consisting of multiple feedback loops. SDM may enable WD researchers and
      practitioners to understand the structure and behavior of the WD system as a
      whole, and inform development of improved strategies to manage straightforward
      and complex WD cases.

PMID- 25864875
TI  - How do demographic and social factors influence parent-offspring conflict? The
      case of wild black and gold howler monkeys (Alouatta caraya).
AB  - In this study, we examined the influence of demography and social context on
      mother-offspring conflict in wild black and gold howler monkeys (Alouatta caraya)
      inhabiting two nearby sites in northern Argentina, one comprising continuous
      forest and one fragmented forest. These sites differed in population density
      (3.25 vs. 1.04 individuals/ha), degree of home range overlap between neighboring
      groups (70 vs. 31%), and rate of intergroup encounters (2 vs. 0.02-1
      encounters/day), though not in interbirth interval or rate of infant mortality.
      During a 27-month study (September 2008 through November 2010), we observed 37
      mother-offspring dyads across the two sites. We found a very similar pattern of
      mother-offspring conflict in both populations; specifically, the sites did not
      differ in any of the variables used to characterize the mother-offspring
      relationship (the time spent in contact, the rate at which the mother makes and
      breaks contact, the rate at which the infant breaks contact, the rate of maternal
      rejection, and signs of infant distress) except one (the rate at which the infant
      makes contact). Although mother-offspring conflict is a dynamic process that
      varies over time, our results suggest that the different demographic and social
      contexts found at the two study sites did not have a marked effect on
      quantitative aspects of the mother-offspring relationship in these populations of
      black and gold howlers. Finally, this study suggests that the environmental
      variability (ecological, demographic, and social traits) leads to a set of
      strategies used both by infants and mothers with a main goal of conflict
      resolution, with mothers specifically aiming to cope with the tradeoff between
      current and future reproduction.

PMID- 25864876
TI  - Dialysis complications in acute kidney injury patients treated with prolonged
      intermittent renal replacement therapy sessions lasting 10 versus 6 hours:
      results of a randomized clinical trial.
AB  - Prolonged intermittent renal replacement therapy (PIRRT) has emerged as an
      alternative to continuous renal replacement therapy in the management of acute
      kidney injury (AKI) patients. This trial aimed to compare the dialysis
      complications occurring during different durations of PIRRT sessions in
      critically ill AKI patients. We included patients older than 18 years with AKI
      associated with sepsis admitted to the intensive care unit and using
      noradrenaline doses ranging from 0.3 to 0.7 ug/kg/min. Patients were divided into
      two groups randomly: in G1, 6-h sessions were performed, and in G2, 10-h sessions
      were performed. Seventy-five patients were treated with 195 PIRRT sessions for 18
      consecutive months. The prevalence of hypotension, filter clotting, hypokalemia,
      and hypophosphatemia was 82.6, 25.3, 20, and 10.6%, respectively. G1 was composed
      of 38 patients treated with 100 sessions, whereas G2 consisted of 37 patients
      treated with 95 sessions. G1 and G2 were similar in male predominance (65.7 vs.
      75.6%, P = 0.34), age (63.6 +/- 14 vs. 59.9 +/- 15.5 years, P = 0.28) and
      Sequential Organ Failure Assessment score (SOFA; 13.1 +/- 2.4 vs. 14.2 +/- 3.0, P
      = 0.2). There was no significant difference between the two groups in hypotension
      (81.5 vs. 83.7%, P = 0.8), filter clotting (23.6 vs. 27%, P = 0.73), hypokalemia
      (13.1 vs. 8.1%, P = 0.71), and hypophosphatemia (18.4 vs. 21.6%, P = 0.72).
      However, the group treated with sessions of 10 h were refractory to clinical
      measures for hypotension, and dialysis sessions were interrupted more often (9.5
      vs. 30.1%, P = 0.03). Metabolic control and fluid balance were similar between G1
      and G2 (blood urea nitrogen [BUN]: 81 +/- 30 vs. 73 +/- 33 mg/dL, P = 1.0;
      delivered Kt/V: 1.09 +/- 0.24 vs. 1.26 +/- 0.26, P = 0.09; actual
      ultrafiltration: 1731 +/- 818 vs. 2332 +/- 947 mL, P = 0.13) and fluid balance (
      731 +/- 125 vs. -652 +/- 141 mL, respectively) . In conclusion, intradialysis
      hypotension was common in AKI patients treated with PIRRT. There was no
      difference in the prevalence of dialysis complications in patients undergoing
      different durations of PIRRT. 

PMID- 25864877
TI  - Morphological MRI characteristics of recent small subcortical infarcts.
AB  - BACKGROUND: New imaging criteria for recent small subcortical infarcts have
      recently been proposed, replacing the earlier term 'lacunar infarction', but
      their applicability and impact on lesion selection is yet unknown. AIMS: To
      collect information on the morphologic characteristics and variability of recent
      small subcortical infarcts on magnetic resonance imaging in regard to lesion
      location and demographic variables. METHODS: We identified all patients with
      acute stroke and cerebral magnetic resonance imaging from 2008 to 2013 in our
      hospital database and selected those with a single recent small subcortical
      infarct defined by an estimated maximal axial diameter of 20 mm. Recent small
      subcortical infarcts were segmented on diffusion-weighted imaging and fluid
      attenuated inversion recovery sequence to calculate the largest axial and
      longitudinal diameter and lesion volume. We assessed morphometric differences of
      recent small subcortical infarcts regarding location and demographic variables
      and the impact of different recent small subcortical infarct definitions on
      lesion selection. RESULTS: Three hundred forty-four patients (median age 72;
      range 25-92 years, 65% male) were selected. Most recent small subcortical
      infarcts were located in the basal ganglia (n = 111), followed by pons (n = 92),
      thalamus (n = 77), and centrum semiovale (n = 64). Quantitative measurements
      confirmed visual assessment of the axial diameter in 95%. All morphometric
      variables were strongly intercorrelated and comparable on diffusion-weighted
      imaging and fluid-attenuated inversion recovery sequence. Recent small
      subcortical infarcts in the basal ganglia were significantly larger both in the
      axial and longitudinal direction compared with other regions. Dichotomization of
      recent small subcortical infarcts according to axial (<= / >15 mm) or
      longitudinal (<= / >20 mm) sizes resulted in different regional frequencies and
      distributions. Age, gender, and time from stroke onset to magnetic resonance
      imaging did not influence lesion metrics or the distribution of recent small
      subcortical infarcts. CONCLUSIONS: Our study confirms the recent neuroimaging
      criteria for recent small subcortical infarcts as a practical concept.
      Definitions of the maximal axial and longitudinal diameter have a significant
      impact on the frequency and distribution of selected infarcts, which has to be
      considered for future studies.

PMID- 25864878
TI  - Oncometabolites: tailoring our genes.
AB  - Increased glucose metabolism in cancer cells is a phenomenon that has been known
      for over 90 years, allowing maximal cell growth through faster ATP production and
      redistribution of carbons towards nucleotide, protein and fatty acid synthesis.
      Recently, metabolites that can promote tumorigeneis by altering the epigenome
      have been identified. These 'oncometabolites' include the tricarboxylic acid
      cycle metabolites succinate and fumarate, whose levels are elevated in rare
      tumours with succinate dehydrogenase and fumarate hydratase mutations,
      respectively. 2-Hydroxyglutarate is another oncometabolite; it is produced de
      novo as a result of the mutation of isocitrate dehydrogenase, and is commonly
      found in gliomas and acute myeloid leukaemia. Interestingly, the structural
      similarity of these oncometabolites to their precursor metabolite, alpha
      ketoglutarate, explains the tumorigenic potential of these metabolites, by
      competitive inhibition of a superfamily of enzymes called the alpha-ketoglutarate
      dependent dioxygenases. These enzymes utilize alpha-ketoglutarate as a
      cosubstrate, and are involved in fatty acid metabolism, oxygen sensing, collagen
      biosynthesis, and modulation of the epigenome. They include enzymes that are
      involved in regulating gene expression via DNA and histone tail demethylation. In
      this review, we will focus on the link between metabolism and epigenetics, and
      how we may target oncometabolite-induced tumorigenesis in the future.

PMID- 25864881
TI  - Clinical evaluation of rosuvastatin in heart transplant patients with
      hypercholesterolemia and therapeutic failure of other statin regimens: short-term
      and long-term efficacy and safety results.
AB  - We conducted an observational study of 30 heart transplant recipients with serum
      low-density lipoprotein cholesterol (LDL-c) >100 mg/dl despite previous statin
      therapy, who were treated with rosuvastatin 10 mg daily (5 mg in case of renal
      dysfunction). Serum lipids, creatine phosphokinase (CPK), bilirubin, and hepatic
      enzymes were prospectively measured 2, 4, and 12 weeks after the initiation of
      the drug. Clinical outcomes of patients who continued on long-term rosuvastatin
      therapy beyond this 12-week period were reviewed in February 2015. Over the 12
      week period following rosuvastatin initiation, serum levels of total cholesterol
      (TC) and LDL-c and the ratio TC/high-density lipoprotein cholesterol (HDL-c)
      decreased steadily (P < 0.001). Average absolute reductions of these three
      parameters were -48.7 mg/dl, -46.6 mg/dl, and -0.9, respectively. Seventeen (57%)
      achieved a serum LDL-c < 100 mg/dl. No significant changes from baseline were
      observed in serum levels of triglycerides, HDL-c, hepatic enzymes, bilirubin, or
      CPK. Twenty-seven (90%) patients continued on long-term therapy with rosuvastatin
      over a median period of 3.6 years, with no further significant variation in lipid
      profile. The drug was suspended due to liver toxicity in 1 (3.3%) patient and due
      to muscle toxicity in 2 (6.7%) patients. All adverse reactions resolved rapidly
      after rosuvastatin withdrawal. Our study supports rosuvastatin as a reasonable
      alternative for heart transplant recipients with hypercholesterolemia and
      therapeutic failure of other statin regimens. 

PMID- 25864879
TI  - Study of the Function of G-Rich Aptamers Selected for Lung Adenocarcinoma.
AB  - Guanine (G)-rich oligonucleotides have attracted considerable interest as
      therapeutic agents. Two G-rich aptamers were selected against epidermal growth
      factor receptor (EGFR)-transfected A549 cells, and their G-rich domains (S13 and
      S50) were identified to account for the binding of parental aptamers. Circular
      dichroism (CD) spectra showed that S13 and S50 bound to their targets by forming
      parallel quadruplexes. Their binding, internalization, and antiproliferation
      activity in cancer and noncancer cells were investigated by flow cytometry and 3
      (4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H
      tetrazolium (MTS) assay, and compared with those of nucleolin-binding AS1411 and
      thrombin-binding aptamer. The two truncated aptamers (S13 and S50) have good
      binding and internalization in cancer cells and noncancer cells; however, only
      S50, similar to AS1411, shows potent antiproliferation against cancer cells. Our
      data suggest that tumor-selective antiproliferation of G-rich oligonucleotides
      does not directly depend on the binding of the G-rich aptamer to cells. 

PMID- 25864882
TI  - Who determines the outcomes of HBV exposure?
AB  - Until recently, the reason for age-dependent immune clearance of hepatitis B
      virus remained elusive. A new study has revealed that establishment of the
      commensal gut microbiota could modulate the liver immunity phenotype in a
      hydrodynamic transfection mouse model, suggesting that natural gut-liver
      interactions can help achieve rapid viral clearance. 

PMID- 25864884
TI  - Hyperthermic intraperitoneal chemotherapy plus simultaneous versus staged
      cytoreductive surgery for gastric cancer with occult peritoneal metastasis.
AB  - BACKGROUND: Our aim is to evaluate the safety and efficacy of two treatment
      strategies, hyperthermic intraperitoneal chemotherapy (HIPEC) plus simultaneous
      versus staged cytoreductive surgery (CRS) in patients with occult peritoneal
      metastasis of gastric cancer (GC). METHODS: We retrospectively reviewed 26 GC
      patients who were potential curatively resectable by pre-operative evaluation and
      found occult peritoneal metastasis by diagnostic laparoscopy. Patients were
      treated by HIPEC plus either simultaneous CRS (CRS+HIPEC group, n = 11) or staged
      CRS after systematic chemotherapy (HIPEC+Chemo+CRS group, n = 15). RESULTS: There
      is no mortality observed in both groups. The treatment complications in two group
      is comparable (P = 0.683), with 26.7% (4/15) in HIPEC+Chemo+CRS group, and 36.4%
      (4/11) in CRS+HIPEC group, respectively. The compliance of patients undergoing
      subsequent chemotherapy is higher in HIPEC+Chemo+CRS group (93.3%, 14/15) than
      that of CRS+HIPEC group (45.5%, 5/11) (P = 0.021). The mean interval time between
      CRS and first post-CRS systematic chemotherapy were 42.0 +/- 12.0 days in
      HIPEC+Chemo+CRS group versus 69.8 +/- 36.3 in CRS+HIPEC group (P = 0.163),
      respectively. The median OS in the HIPEC+Chemo+CRS group was 25.0 months, while
      28.2 months in the CRS+HIPEC group (P = 0.738). CONCLUSION: For resectable GC
      patients with laparoscopic findings of occult peritoneal metastasis, HIPEC plus
      staged CRS is with better tolerance and compliance than simultaneous CRS.

PMID- 25864885
TI  - Preparation and Regioselective Magnesiation or Lithiation of
      Bis(trimethylsilyl)methyl-Substituted Heteroaryls for the Generation of Highly
      Functionalized Heterocycles.
AB  - A wide range of bis(trimethylsilyl)methyl (BTSM)- substituted heteroaryl
      derivatives has been prepared by using Kumada-Corriu or Negishi cross-coupling
      reactions. The regioselective lithiation or magnesiation of these building blocks
      bearing a bulky BTSM group by using magnesium or lithium 2,2,6,6
      tetramethylpiperidide bases followed by quenching reactions with different
      electrophiles provides various functionalized N-, O-, or S-heterocycles.
      Furthermore, the BTSM group can then be converted into formyl, methyl, or styryl
      groups to give access to a variety of highly functionalized heteroaromatics. 

PMID- 25864883
TI  - Staphylococcus aureus infections: transmission within households and the
      community.
AB  - Staphylococcus aureus, both methicillin susceptible and resistant, are now major
      community-based pathogens worldwide. The basis for this is multifactorial and
      includes the emergence of epidemic clones with enhanced virulence, antibiotic
      resistance, colonization potential, or transmissibility. Household reservoirs of
      these unique strains are crucial to their success as community-based pathogens.
      Staphylococci become resident in households, either as colonizers or
      environmental contaminants, increasing the risk for recurrent infections.
      Interactions of household members with others in different households or at
      community sites, including schools and daycare facilities, have a critical role
      in the ability of these strains to become endemic. Colonization density at these
      sites appears to have an important role in facilitating transmission. The
      integration of research tools, including whole-genome sequencing (WGS),
      mathematical modeling, and social network analysis, has provided additional
      insight into the transmission dynamics of these strains. Thus far, interventions
      designed to reduce recurrent infections among household members have had limited
      success, likely due to the multiplicity of potential sources for recolonization.
      The development of better strategies to reduce the number of household-based
      infections will depend on greater insight into the different factors that
      contribute to the success of these uniquely successful epidemic clones of S.
      aureus. 

PMID- 25864886
TI  - Association of the Plasma Platelet-Derived Microparticles to Platelet Count Ratio
      with Hospital Mortality and Disseminated Intravascular Coagulopathy in Critically
      Ill Patients.
AB  - AIM: The role of platelet-derived microparticles (PDMPs) in the crosstalk between
      coagulopathy and inflammation in critically ill patients remains unclear. The aim
      of this cohort observational study was to investigate the associations between
      the PDMP levels and hospital mortality or disseminated intravascular coagulopathy
      (DIC). METHODS: This study included 119 patients who were admitted to the ICU.
      The PDMP levels were measured using an enzyme-linked immunosorbent assay three
      times a week, for a total of 372 samples. We calculated the maximum (max) PDMP
      value, max PDMP/platelet (PDMP/Plts) ratio (converted to the PDMP levels per
      10(4) platelets) and nadir platelet count during the ICU stay. Baseline patient
      data and scores, including the Japanese Association for Acute Medicine (JAAM) DIC
      score, were collected, and potential predictors were analyzed for possible
      associations with hospital mortality. RESULTS: The max PDMP/Plts ratio was
      significantly different comparing the survivors (n=98: median, 2.54) and non
      survivors (n=21: median 17.59; p<0.001). There was a weak but statistically
      significant negative correlation between the max PDMP level and nadir platelet
      count (r=-0.332, p<0.001). The max PDMP level and max PDMP/Plts ratio were higher
      in the DIC group (81.48 and 9.27, respectively) than in the non-DIC group (34.88
      and 2.35, p=0.001 and p<0.001, respectively). The max PDMP/Plts ratio was the
      only variable found to be independently associated with hospital mortality
      according to a multivariate logistic regression analysis. CONCLUSIONS: PDMPs are
      involved in the development of DIC but are not related to hospital mortality.
      There is a good association between the PDMP/Plts ratio and hospital mortality
      and/or DIC in critically ill patients.

PMID- 25864887
TI  - Different Impacts of Cardiovascular Risk Factors on Arterial Stiffness versus
      Arterial Wall Thickness in Japanese Patients with Type 2 Diabetes Mellitus.
AB  - AIM: We statistically investigated whether the impact of cardiovascular risk
      factors on arterial stiffness would be different from that on arterial wall
      thickness. METHODS: We analyzed 1648 Japanese type 2 diabetic patients. Arterial
      stiffness was evaluated by pulse wave verbosity (PWV) and wall thickness was
      assessed with carotid intima-media thickness (IMT) by ultrasonography. We
      developed a common regression model to PWV and IMT by extending the linear mixed
      model and statistically detected the difference in the impact of cardiovascular
      risk factors between the two indices. RESULTS: There was a significant
      correlation between PWV and IMT (r=0.365, p < 0.001). Sex, diabetic duration,
      hemoglobin A1c levels, and the presence of retinopathy and cardiovascular disease
      were comparable independent risk factors for elevated PWV and IMT. On the other
      hand, the impact of age, systolic blood pressure, and low- and high-density
      lipoprotein cholesterol levels were significantly different between the two
      measurements (all p < 0.05). Cholesterol levels were significantly associated
      with IMT but not with PWV. Age and systolic blood pressure had a significant
      impact on both measurements, but the impact on PWV was significantly greater than
      that on IMT. Indeed, patients with low IMT but with advanced age and high
      systolic pressure had high PWV, whereas patients with low PWV but with impaired
      cholesterol levels had high IMT. CONCLUSION: The extended linear mixed model
      statistically confirmed that the impact of cardiovascular risk factors on
      elevated PWV and IMT were not identical in Japanese patients with type 2 diabetes
      mellitus.

PMID- 25864888
TI  - Chirality separation of mixed chiral microswimmers in a periodic channel.
AB  - Dynamics and separation of mixed chiral microswimmers are numerically
      investigated in a channel with regular arrays of rigid half-circle obstacles. For
      zero shear flow, transport behaviors are the same for different chiral particles:
      the average velocity decreases with increase of the rotational diffusion
      coefficient, the direction of the transport can be reversed by tuning the angular
      velocity, and there exists an optimal value of the packing fraction at which the
      average velocity takes its maximal value. However, when the shear flow is
      considered, different chiral particles show different behaviors. By suitably
      tailoring parameters, particles with different chiralities can move in different
      directions and can be separated. In addition, we also proposed a space separation
      method by introducing a constant load, where counterclockwise and clockwise
      particles stay in different regions of the channel. 

PMID- 25864889
TI  - Shiga toxin-1 Decreases Endothelial Cell Tissue Factor Pathway Inhibitor Not Co
      localized with Tissue Factor on the Cell Membrane.

PMID- 25864890
TI  - Mapping the Possibilities: Using Network Analysis to Identify Opportunities for
      Building Nutrition Partnerships Within Diverse Low-Income Communities.
AB  - OBJECTIVE: To identify communication and collaboration patterns among
      organizations involved in nutrition education within an ethnically diverse low
      income community. DESIGN: A snowball sample methodology was used to identify 27
      organizations involved in nutrition activities in the community. The researchers
      conducted an online survey and network analysis to identify communication and
      collaboration patterns among these organizations. SETTING: An urban neighborhood
      in Honolulu, HI. PARTICIPANTS: Individuals responsible for nutrition activities
      at state, county, and nonprofit organizations. MAIN OUTCOME MEASURES: Network
      structure, betweenness, and centralization. ANALYSIS: Communication was
      uncentralized and collaboration was limited. Collaboration was affected by
      differences in mission, location, and population served. Child care/youth
      development organizations and community health centers provided links across the
      community. Agencies serving different ethnic populations were poorly linked and
      located on the periphery of the network. Ethnic-specific churches expressed
      strong interest in nutrition partnership but were not identified as potential
      partners by other agencies in the network. CONCLUSIONS AND IMPLICATIONS: Limited
      communication between agencies serving different populations in the same
      community may result in missed opportunities for collaboration. Network analysis
      is an effective tool for identifying these gaps and helps build community
      capacity for improving nutrition outcomes.

PMID- 25864891
TI  - Patient-derived measures of GI endoscopy: a meta-narrative review of the
      literature.
AB  - BACKGROUND AND AIMS: GI endoscopy (GIE) is widely performed, with 1 in 3 people
      requiring an endoscopic procedure at some point. Patient experience of medical
      procedures is important, but, to date, experience measures of GIE are derived
      from clinician opinion rather than from patients themselves. In this meta
      narrative review, the literature on methods of assessing patient experience in
      GIE is reported. METHODS: ScienceDirect, MEDLINE, Web of Knowledge, Web of
      Science, CINAHL, and PsycINFO were searched to November 2013 using meta-narrative
      standards. Search terms included those related to endoscopic procedures, combined
      with those related to patient experience. RESULTS: A total of 3688 abstracts were
      identified and reviewed for relevance. A total of 3549 were excluded, leaving 139
      for full-text review. We subsequently included 48 articles. Three sub-groups of
      studies were identified--those developing original measures of endoscopy-specific
      patient experience (27 articles), those modifying existing measures (10
      articles), and those testing existing measures for reliability or validity (11
      articles). Most measures focused on pain, discomfort, anxiety, and embarrassment.
      Three studies explored wider aspects of experience, including preparation, unit
      organization, and endoscopist preference. Likert scales, visual analog scale
      scores, and questionnaires were used most commonly. The Global Rating Scale was
      validated for use in 2 studies, confirming that those domains cover all aspects
      of endoscopy experience. Other measures were modified to assess endoscopic
      experience, such as the modified Group Health Association of America survey
      (mGHAA-9) (modified by 5 studies). CONCLUSIONS: No patient-derived and validated
      endoscopy-specific experience measures were found. Patient-derived and validated
      experience measures should be developed and used to model optimal healthcare
      delivery.

PMID- 25864892
TI  - Endoscopic hang time: can we get some clarity?

PMID- 25864893
TI  - Endoscopic therapy of high-grade dysplasia and intramucosal adenocarcinoma: 2
      small steps for the endoscopists but a fine step forward for the patient.

PMID- 25864894
TI  - Should we consider POEMs for refractory nonachalasia, spastic esophageal
      disorders? A guarded yes!

PMID- 25864895
TI  - EUS: a panacea for detection of peritoneal carcinomatosis!

PMID- 25864896
TI  - EUS-guided gastroenterostomy: a new promising technique in evolution.

PMID- 25864897
TI  - Weekend admission in upper GI bleeding: does it have an impact on outcome?

PMID- 25864898
TI  - Response.

PMID- 25864899
TI  - High-grade dysplasia in thoracic inlet patch treated by focal endoscopic mucosal
      resection and radiofrequency ablation.

PMID- 25864900
TI  - What goes in should not always come out: migration of a prosthetic mesocaval
      shunt via erosion through the duodenum.

PMID- 25864901
TI  - Development of an endosonography app: a smart device for continuous education.

PMID- 25864902
TI  - EUS-guided tissue acquisition: things are not always what they seem.

PMID- 25864903
TI  - Response.

PMID- 25864904
TI  - Making the GRADE.

PMID- 25864905
TI  - An unusual foreign body in the ileum.

PMID- 25864907
TI  - Carbon Nanotubes for Dye-Sensitized Solar Cells.
AB  - As one type of emerging photovoltaic cell, dye-sensitized solar cells (DSSCs) are
      an attractive potential source of renewable energy due to their eco-friendliness,
      ease of fabrication, and cost effectiveness. However, in DSSCs, the rarity and
      high cost of some electrode materials (transparent conducting oxide and platinum)
      and the inefficient performance caused by slow electron transport, poor light
      harvesting efficiency, and significant charge recombination are critical issues.
      Recent research has shown that carbon nanotubes (CNTs) are promising candidates
      to overcome these issues due to their unique electrical, optical, chemical,
      physical, as well as catalytic properties. This article provides a comprehensive
      review of the research that has focused on the application of CNTs and their
      hybrids in transparent conducting electrodes (TCEs), in semiconducting layers,
      and in counter electrodes of DSSCs. At the end of this review, some important
      research directions for the future use of CNTs in DSSCs are also provided. 

PMID- 25864906
TI  - Effect of Different Meditation Types on Migraine Headache Medication Use.
AB  - Spiritual meditation has been found to reduce the frequency of migraines and
      physiological reactivity to stress. However, little is known about how
      introducing a spirituality component into a meditation intervention impacts
      analgesic medication usage. In this study, 92 meditation-naive participants were
      randomly assigned to one of four groups: (1) Spiritual Meditation, (n = 25), (2)
      Internally Focused Secular Meditation (n = 23), (3) Externally Focused Secular
      Meditation (n = 22), or (4) Progressive Muscle Relaxation (n = 22); and practiced
      their technique for 20 min/day over 30 days while completing daily diaries.
      Headache frequency, headache severity, and pain medication use were assessed.
      Migraine frequency decreased in the Spiritual Meditation group compared to other
      groups (p < 0.05). Headache severity ratings did not differ across groups (p =
      ns). After adjusting for headache frequency, migraine medication usage decreased
      in the Spiritual Meditation group compared to other groups (p < 0.05). Spiritual
      Meditation was found to not affect pain sensitivity, but it does improve pain
      tolerance with reduced headache related analgesic medication usage.

PMID- 25864908
TI  - The role of multifunctional drug therapy as an antidote to combat experimental
      subacute neurotoxicity induced by organophosphate pesticides.
AB  - Organophosphate pesticides are used in agriculture where they are associated with
      numerous cases of intentional and accidental misuse. These toxicants are potent
      inhibitors of cholinesterases leading to a massive build-up of acetylcholine
      which induces an array of deleterious effects, including convulsions, oxidative
      damage and neurobehavioral deficits. Antidotal therapies with atropine and oxime
      yield a remarkable survival rate, but fail to prevent neuronal damage and
      behavioral problems. It has been indicated that multifunction drug therapy with
      potassium channel openers, calcium channel antagonists and antioxidants (either
      single-agent therapy or combination therapy) may have the potential to prevent
      cell death and/or slow down the processes of secondary neuronal damage. The aim
      of the present study, therefore, was to make a relative assessment of the
      potential effects of nicorandil (2 mg/kg), clinidipine (10 mg/kg), and grape seed
      proanthocyanidin (GSPE) extract (200 mg/kg) individually against subacute
      chlorpyrifos induced toxicity. The test drugs were administered to Wistar rats 2
      h after exposure to Chlorpyrifos (CPF). Different behavioral studies and
      biochemical estimation has been carried in the study. The results showed that
      chronic administration of CPF significantly impaired learning and memory, along
      with motor coordination, and produced a marked increase in oxidative stress along
      with significantly reduced acetylcholine esterase (AChE) activity. Treatment with
      nicorandil, clinidipine and GSPE was shown to significantly improve memory
      performance, attenuate oxidative damage and enhance AChE activity in rats. The
      present study also suggests that a combination of nicorandil, clinidipine, and
      GSPE has a better neuroprotective effect against subacute CPF induced
      neurotoxicity than if applied individually. (c) 2015 Wiley Periodicals, Inc.
      Environ Toxicol 31: 1017-1026, 2016. 

PMID- 25864909
TI  - Prevalence of ADHD in primary school children in Vinh Long, Vietnam.
AB  - BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is the most common
      behavioral disorder in children. It affects not only the subjects but also their
      families and society. The purpose of this study was to determine the prevalence
      of ADHD in primary school children in South Vietnam, especially Vinh Long
      province. METHOD: Children were chosen randomly from primary schools in Vinh Long
      from February to March in 2009 in a cross-sectional study to determine the
      prevalence of ADHD using the ADHD Rating Scale-IV for parents/caregivers and
      teachers. ADHD Rating Scale-IV was based on DSM-IV for diagnosis of ADHD.
      RESULTS: A total of 600 children were chosen and 1200 reports were collected from
      parents/caregivers and teachers. The prevalence rate of ADHD was 7.7%. The rates
      of the predominantly inattentive type, predominantly hyperactive type and
      combined type were 1.7%, 5% and 1%, respectively. The difference in sex was not
      significant across all subtypes. The prevalence of ADHD in urban children was 2.2
      fold that in rural children. CONCLUSION: The prevalence of ADHD in primary school
      children in Vinh Long, southern Vietnam, is in the same range as other regions in
      the world. Therefore, awareness of ADHD needs to be raised, to ensure suitable
      psychiatric care for children.

PMID- 25864910
TI  - On the Origin of SERKs: Bioinformatics Analysis of the Somatic Embryogenesis
      Receptor Kinases.
AB  - Somatic embryogenesis receptor-like kinases (SERKs) are leucine-rich repeat
      receptor-like kinases involved in several, seemingly unrelated, plant-signaling
      pathways. In Arabidopsis thaliana, functional and genetic analysis of four SERK
      proteins has indicated that they are only partly redundant; their functions
      overlap but each performs a specific subset of signaling roles. The molecular
      basis for the functional specificity within this highly homologous protein family
      is currently not known. Sequence analysis of SERK proteins from different plant
      species indicates that the SERKs are a highly conserved protein family present in
      monocots, dicots, and non-vascular plants. Residues in the extracellular domain
      that are important for interaction with other receptor kinases are highly
      conserved, even among SERK members without a function in the corresponding
      pathways. SERK2, for instance, does not function in the brassinosteroid pathway,
      does not interact with BRI1, but is conserved in its BRI1-interacting domain.
      Further sequence analysis indicates that SERK3/BAK1 and SERK4/BKK1 have diverged
      from the original SERK protein in both their extracellular and cytoplasmic
      domains. Functional analysis of chimeric SERK proteins shows that different
      domains provide the SERK proteins with different functional specificity. For
      instance, the SERK1 or SERK2 extracellular domains are essential for SERK
      function in male sporogenesis, while the SERK3 extracellular and cytoplasmic
      domains are essential for SERK3 activity in brassinosteroid and flagellin
      signaling. The emerging picture is that SERKs are ancient genes, whose products
      have been recruited as co-receptors in the newly evolved signaling pathways. The
      SERK ligand-binding and protein-protein interaction domains are highly conserved,
      allowing all SERKs to form complexes, albeit with different affinity. However,
      specific functional residues must have been altered, in both the extracellular
      and intracellular domains, to allow for the observed differences in
      functionality.

PMID- 25864911
TI  - Use of HSI to measure oxygen saturation in the lower limb and its correlation
      with healing of foot ulcers in diabetes.
AB  - AIM: To explore the use of hyperspectral imaging (HSI) to predict healing of
      diabetic foot ulcers in patients with diabetes. METHODS: We used a HSI technique
      that incorporated novel software to account for tissue scattering of light, and
      was validated using blood samples of varying oxygen saturation assessed by blood
      gas analysis. HSI was then performed on a population newly presenting with
      diabetic foot ulcers to a specialist clinic, and associations were sought with
      healing at 12 and 24 weeks. RESULTS: The correlation between the results of HSI
      and blood gas analysis was strong (r = 0.994). A total of 43 patients (mean +/-
      sd age 62.7 +/- 12.2 years; 31 men, 12 women; 37 with Type 2 diabetes, six with
      Type 1 diabetes) with foot ulcers were included in the prospective clinical study
      and underwent HSI within 16 days of presentation. In all, 26 ulcers healed within
      12 weeks and 28 within 24 weeks. There was a negative association between tissue
      oxygenation assessed by HSI at baseline and healing by 12 weeks (P = 0.009), and
      this was observed in both infected and non-infected ulcers. There was a
      significant positive correlation between oxygenation assessed by HSI and time to
      healing (P = 0.03). No correlations were observed at 24 weeks. CONCLUSIONS: These
      findings suggest that HSI may predict healing in routine practice. The fact that
      the correlation between HSI and healing was negative could be explained by HSI
      being a measure of oxygenation of haemoglobin and there may be an inverse
      relationship between this and the oxygenation of extravascular tissue in people
      with neuropathy and/or microvascular disease.

PMID- 25864912
TI  - Expression of angiopoietin-like protein 4 at the fracture site: Regulation by
      hypoxia and osteoblastic differentiation.
AB  - Vascular disruption that occurs as a consequence of bone fracture, leads to
      hypoxia at the site of damage. Hypoxia regulates the expression of a number of
      genes that can modulate energy conservation, cell survival, tissue regeneration
      and angiogenesis. In this study we investigated the expression of Angiopoietin
      like 4, an adipocytokine that has additional roles in angiogenesis, at the
      fracture site. We demonstrate that Angptl4 mRNA expression increased early during
      fracture healing (day 3) returning close to baseline at day14. In the callus,
      Angptl4 mRNA was visualized in areas of condensing mesenchymal cells, callus
      cartilage and was especially high in mineralizing osteoblasts located in areas of
      new bone formation. In vitro, Angptl4 mRNA expression in osteoblasts increased
      under hypoxic conditions and in cells treated with the hypoxia mimetic
      desferrioxamine. Angptl4 levels were strongly induced at day 14 in
      differentiating MC3T3-E1 osteoblastic cells. Exogenous ANGPTL4 increased
      expression of Runx2, Spp1, vegfa, and Alp mRNA in differentiating osteoblasts. We
      suggest that the distribution of Angptl4 in the callus may be driven by hypoxia
      and that Angptl4 may play a role in osteoblastic differentiation, and possibly
      angiogenesis via regulation of VEGF. Further studies could reveal a dual role for
      Angptl4 in angiogenesis and osteogenesis.

PMID- 25864913
TI  - Motor and neurocognitive recovery in the syndrome of the trephined: A case
      report.

PMID- 25864914
TI  - Overview of the special issue on HBV immunity.

PMID- 25864915
TI  - The promise of gammadelta T cells and the gammadelta T cell receptor for cancer
      immunotherapy.
AB  - gammadelta T cells form an important part of adaptive immune responses against
      infections and malignant transformation. The molecular targets of human
      gammadelta T cell receptors (TCRs) remain largely unknown, but recent studies
      have confirmed the recognition of phosphorylated prenyl metabolites, lipids in
      complex with CD1 molecules and markers of cellular stress. All of these molecules
      are upregulated on various cancer types, highlighting the potential importance of
      the gammadelta T cell compartment in cancer immunosurveillance and paving the way
      for the use of gammadelta TCRs in cancer therapy. Ligand recognition by the
      gammadelta TCR often requires accessory/co-stimulatory stress molecules on both T
      cells and target cells; this cellular stress context therefore provides a
      failsafe against harmful self-reactivity. Unlike alphabeta T cells, gammadelta T
      cells recognise their targets irrespective of HLA haplotype and therefore offer
      exciting possibilities for off-the-shelf, pan-population cancer immunotherapies.
      Here, we present a review of known ligands of human gammadelta T cells and
      discuss the promise of harnessing these cells for cancer treatment.

PMID- 25864916
TI  - HAX1 deletion impairs BCR internalization and leads to delayed BCR-mediated
      apoptosis.
AB  - Deletion of HAX1 in mice causes a severe reduction in the numbers of lymphocytes
      in the bone marrow and in the spleen. Additionally, B220(+) B progenitor cells in
      the bone marrow are reduced, suggesting an important function of HAX1 in B cell
      development. HAX1 is thought to play a protective role in apoptotic processes;
      therefore, we investigated the role of HAX1 in bone marrow B progenitor cells and
      splenic B cells. We did not observe an effect on the survival of Hax1(-/-) bone
      marrow cells but detected enhanced survival of splenic Hax1(-/-) B cells upon in
      vitro starvation/growth-factor withdrawal. To explain this apparent inconsistency
      with previous reports of HAX1 function, we also studied the B cell receptor (BCR)
      induced apoptosis of IgM-stimulated splenic naive B cells and found that
      apoptosis decreased in these cells. We further found impaired internalization of
      the BCR from Hax1(-/-) splenic B cells after IgM crosslinking; this impaired
      internalization may result in decreased BCR signaling and, consequently,
      decreased BCR-mediated apoptosis. We measured HAX1 binding to the cytoplasmic
      domains of different Ig subtypes and identified KVKWI(V)F as the putative binding
      motif for HAX1 within the cytoplasmic domains. Because this motif can be found in
      almost all Ig subtypes, it is likely that HAX1 plays a general role in BCR
      mediated internalization events and BCR-mediated apoptosis.

PMID- 25864918
TI  - Docosahexaenoic Acid with a statin and endothelial function in patients with
      coronary artery disease.

PMID- 25864917
TI  - Chimerically fused antigen rich of overlapped epitopes from latent membrane
      protein 2 (LMP2) of Epstein-Barr virus as a potential vaccine and diagnostic
      agent.
AB  - Epstein-Barr virus (EBV) is prevalent throughout the world and is associated with
      several malignant diseases in humans. Latent membrane protein 2 (LMP2) of EBV
      plays a crucial role in the pathogenesis of EBV-associated tumors; therefore,
      LMP2 has been considered to be a potential immunodiagnostic and immunotherapeutic
      target. A multi-epitope-based antigen is a promising option for therapeutic
      vaccines and diagnoses of such malignancies. In this study, we systematically
      screened cytotoxic T lymphocyte (CTL), helper T cell (Th) and B-cell epitopes
      within EBV-LMP2 using bioinformatics. Based on the screen, two peptides rich in
      overlapping epitopes of both T cells and B cells were selected to construct a
      plasmid containing the sequence for a chimeric multi-epitope protein referred to
      as EBV-LMP2m, which is composed of LMP2aa195~232 and LMP2aa419~436. The EBV-LMP2m
      protein was expressed in E. coli BL21 (DE3) after prokaryotic codon optimization.
      Inoculation of the purified chimeric antigen in BALB/c mice induced not only high
      levels of specific IgG in the serum and secretory IgA in the vaginal mucus but
      also a specific CTL response. By using purified EBV-LMP2m as an antigen, the
      presence of specific IgG in the serum specimens of 202 nasopharyngeal carcinoma
      (NPC) patients was effectively detected with 52.84% sensitivity and 95.40%
      specificity, which represents an improvement over the traditional detection
      method based on VCA-IgA (60.53% sensitivity and 76.86% specificity). The above
      results indicate that EBV-LMP2m may be used not only as a potential target
      antigen for EBV-associated tumors but also a diagnostic agent for NPC patients.

PMID- 25864919
TI  - Impaired dendritic inhibition leads to epileptic activity in a computer model of
      CA3.
AB  - Temporal lobe epilepsy (TLE) is a common type of epilepsy with hippocampus as the
      usual site of origin. The CA3 subfield of hippocampus is reported to have a low
      epileptic threshold and hence initiates the disorder in patients with TLE. This
      study computationally investigates how impaired dendritic inhibition of pyramidal
      cells in the vulnerable CA3 subfield leads to generation of epileptic activity. A
      model of CA3 subfield consisting of 800 pyramidal cells, 200 basket cells (BC)
      and 200 Oriens-Lacunosum Moleculare (O-LM) interneurons was used. The dendritic
      inhibition provided by O-LM interneurons is reported to be selectively impaired
      in some TLEs. A step-wise approach is taken to investigate how alterations in
      network connectivity lead to generation of epileptic patterns. Initially,
      dendritic inhibition alone was reduced, followed by an increase in the external
      inputs received at the distal dendrites of pyramidal cells, and finally
      additional changes were made at the synapses between all neurons in the network.
      In the first case, when the dendritic inhibition of pyramidal cells alone was
      reduced, the local field potential activity changed from a theta-modulated gamma
      pattern to a prominently gamma frequency pattern. In the second case, in addition
      to this reduction of dendritic inhibition, with a simultaneous large increase in
      the external excitatory inputs received by pyramidal cells, the basket cells
      entered a state of depolarization block, causing the network to generate a
      typical ictal activity pattern. In the third case, when the dendritic inhibition
      onto the pyramidal cells was reduced and changes were simultaneously made in
      synaptic connectivity between all neurons in the network, the basket cells were
      again observed to enter depolarization block. In the third case, impairment of
      dendritic inhibition required to generate an ictal activity pattern was lesser
      than the two previous cases. Moreover, the ictal like activity began earlier in
      the third case. Hence, our study suggests that greater synaptic plasticity
      occurring in the whole network due to increase in reception of external
      excitatory inputs (due to impaired dendritic inhibition) makes the network more
      susceptible to generation of epileptic activity.

PMID- 25864920
TI  - Hepatoprotective effect of Commiphora myrrha against d-GalN/LPS-induced hepatic
      injury in a rat model through attenuation of pro inflammatory cytokines and
      related genes.
AB  - CONTEXT: Commiphora myrrha (Burseraceae), a shrub resembling a small tree, has
      been used for several centuries for the treatment of various diseases. OBJECTIVE:
      This study investigates the hepatoprotective activity of C. myrrha ethanol
      extract against d-galactosamine/lipopolysaccharide (d-GalN/LPS)-induced acute
      hepatic injury in an animal model. MATERIALS AND METHODS: Rats were pretreated
      with ethanolic extract C. myrrha (250 and 500 mg/kg; p.o.) for 7 d prior to the
      induction of an acute phase response by d-GalN/LPS. Animals were sacrificed 24 h
      after d-GalN/LPS (800 mg/kg and 50 ug/kg i.p.) administration for the biochemical
      and histological analyses. RESULTS: The administration of d-GalN/LPS increased
      plasma aminotransferases (174.47 +/- 4.5761 and 260.96 +/- 1.9839 ukat/l) and
      total bilirubin levels (1.012 +/- 0.0288 mg/dl), which were attenuated by C.
      myrrha treatment. Hepatic lipid peroxidation activity and nitric oxide content
      also increased, while the antioxidant activity measured by GSH (0.76 nmol/g
      protein), SOD (81.91 U/mg protein), and CAT (15.78 U/mg protein) was reduced.
      Commiphora myrrha provided significant restoration of GSH (0.815 nmol/gm
      protein), SOD (140.57 U/mg protein), and CAT (27.02 U/mg protein) levels.
      Furthermore, the acute phase response elicited by d-GalN/LPS administration
      enhanced mRNA expressions of TNF-alpha, IL-6, IL-10, iNOS-2, and HO-1, which were
      ameliorated by C. myrrha treatment. DISCUSSION AND CONCLUSION: These findings
      indicate that C. myrrha considerably reduces the oxidative stress of d-GalN/LPS
      induced hepatic injury via multiple pathways including adown regulation of
      inflammatory mediators and cytokines. Such a property might be sufficient to
      combat cellular damage caused by various conditions that resemble fulminant
      hepatitis and could be of a potential clinical application.

PMID- 25864921
TI  - Four- to Six-Year-Old Children's Sensitivity to Reliability Versus Consensus in
      the Endorsement of Object Labels.
AB  - Recent studies have demonstrated that young children use past reliability and
      consensus to endorse object labels. Until now, no study has investigated how
      children weigh these two cues when they are in conflict. The two experiments
      reported here were designed to explore whether any initial preference for
      information provided by a consensual group would be influenced by the group's
      subsequent unreliability. The results show that 4- and 5-year-old children were
      more likely to endorse labels provided by an unreliable but consensual group than
      the labels provided by a reliable dissenter. Six-year-olds displayed the reverse
      pattern. The article concludes by discussing the methodological implications of
      the two experiments and the developmental trajectory regarding the way children
      weigh consensuality versus reliability.

PMID- 25864923
TI  - Nanoheterogeneous catalysis in electrochemically induced olefin
      perfluoroalkylation.
AB  - Ni-catalyzed electroreductive olefin perfluoroalkylation affords both monomeric
      and dimeric products depending on the reaction media. Recycling of the catalyst
      can be achieved by immobilization of a (bpy)NiBr2 complex on silica nanoparticles
      decorated with anchoring amino-groups. Switching the homogeneous and
      heterogeneous catalysts is found to be one more factor to control the product
      ratio. This catalytic technique is both green and atom economical and combines
      the advantages of nanoheterogeneous catalysis and electrocatalysis. 

PMID- 25864922
TI  - Reelin supplementation recovers synaptic plasticity and cognitive deficits in a
      mouse model for Angelman syndrome.
AB  - The Reelin signaling pathway is implicated in processes controlling synaptic
      plasticity and hippocampus-dependent learning and memory. A single direct in vivo
      application of Reelin enhances long-term potentiation, increases dendritic spine
      density and improves associative and spatial learning and memory. Angelman
      syndrome (AS) is a neurological disorder that presents with an overall defect in
      synaptic function, including decreased long-term potentiation, reduced dendritic
      spine density, and deficits in learning and memory, making it an attractive model
      in which to examine the ability of Reelin to recover synaptic function and
      cognitive deficits. In this study, we investigated the effects of Reelin
      administration on synaptic plasticity and cognitive function in a mouse model of
      AS and demonstrated that bilateral, intraventricular injections of Reelin recover
      synaptic function and corresponding hippocampus-dependent associative and spatial
      learning and memory. Additionally, we describe alteration of the Reelin profile
      in tissue from both the AS mouse and post-mortem human brain. 

PMID- 25864924
TI  - The genes Scgb1a1, Lpo and Gbp2 characteristically expressed in peri-implant
      epithelium of rats.
AB  - OBJECTIVES: The peri-implant epithelium (PIE) plays an important role in the
      prevention against initial stage of inflammation. To minimize the risk of peri
      implantitis, it is necessary to understand the biological characteristics of the
      PIE. The aim of this study was to investigate the characteristic gene expression
      profile of PIE as compared to junctional epithelium (JE) using laser
      microdissection and microarray analysis. METHODS: Left upper first molars of 4
      week-old rat were extracted, and titanium alloy implants were placed. Four weeks
      after surgery, samples were harvested by laser microdissection, and total RNA
      samples were isolated. Comprehensive analyses of genes expressed in the JE and
      PIE were performed using microarray analysis. Confirmation of the differential
      expression of selected genes was performed by quantitative real-time polymerase
      chain reaction and immunohistochemistry. RESULTS: The microarray analysis showed
      that 712 genes were more than twofold change upregulated in the PIE compared with
      the JE. Genes Scgb1a1 were significantly upregulated more than 19.1-fold, Lpo
      more than 19.0-fold, and Gbp2 more than 8.9-fold, in the PIE (P < 0.01).
      Immunohistochemical localization of SCGB1A1, LPO, and GBP2 was observed in PIE.
      CONCLUSION: The present results suggested that genes Scgb1a1, Lpo, and Gbp2 are
      characteristically expressed in the PIE.

PMID- 25864925
TI  - Tumor vessel up-regulation of INSR revealed by single-cell expression analysis of
      the tyrosine kinome and phosphatome in human cancers.
AB  - The tyrosine kinome and phosphatome harbor oncogenes and tumor suppressor genes
      and important regulators of angiogenesis and tumor stroma formation. To provide a
      better understanding of their potential roles in cancer, we analyzed the
      expression of 85 tyrosine kinases and 42 tyrosine phosphatases by in situ
      hybridization 48 human normal and 24 tumor tissue specimens. Nine-tenths of the
      assessed transcripts had tumor cell expression concordant with expression array
      databases. Further, pan-cancer expression of AATK, PTPRK, and PTPRU and
      expression of PTPRS in a subset of tumors were observed. To demonstrate tumor
      subcompartment resolution, we validated the predicted tumor stroma-specific
      markers HTRA1, HTRA3, MXRA5, MXRA8, and SERPING1 in situ. In addition to known
      vascular and stromal markers such as PDGFRB, we observed stromal expression of
      PTK6 and TNS1 and vascular expression of INSR, PTPRF, PTPRG, PTPRU, and TNS1, of
      which INSR emerged as a tumor-specific vessel marker. This study demonstrates the
      feasibility of large-scale analyses to chart the transcriptome in situ in human
      cancers and their ability to identify novel cancer biomarkers. 

PMID- 25864927
TI  - Uncovering phase-coupled oscillatory networks in electrophysiological data.
AB  - Phase consistent neuronal oscillations are ubiquitous in electrophysiological
      recordings, and they may reflect networks of phase-coupled neuronal populations
      oscillating at different frequencies. Because neuronal oscillations may reflect
      rhythmic modulations of neuronal excitability, phase-coupled oscillatory networks
      could be the functional building block for routing information through the brain.
      Current techniques are not suited for directly characterizing such networks. To
      be able to extract phase-coupled oscillatory networks we developed a new method,
      which characterizes networks by phase coupling between sites. Importantly, this
      method respects the fact that neuronal oscillations have energy in a range of
      frequencies. As a consequence, we characterize these networks by between-site
      phase relations that vary as a function of frequency, such as those that result
      from between-site temporal delays. Using human electrocorticographic recordings
      we show that our method can uncover phase-coupled oscillatory networks that show
      interesting patterns in their between-site phase relations, such as travelling
      waves. We validate our method by demonstrating it can accurately recover
      simulated networks from a realistic noisy environment. By extracting phase
      coupled oscillatory networks and investigating patterns in their between-site
      phase relations we can further elucidate the role of oscillations in neuronal
      communication.

PMID- 25864926
TI  - The epithelial danger signal IL-1alpha is a potent activator of fibroblasts and
      reactivator of intestinal inflammation.
AB  - Intestinal epithelial cell (IEC) death is typical of inflammatory bowel disease
      (IBD). We investigated: i) whether IEC-released necrotic cell products
      (proinflammatory mediators) amplify mucosal inflammation, ii) the capacity of
      necrotic cell lysates from HT29 cells or human IECs to induce human intestinal
      fibroblasts' (HIF) production of IL-6 and IL-8, and iii) whether IL-1alpha,
      released by injured colonocytes, exacerbated experimental IBD. Necrotic cell
      lysates potently induced HIF IL-6 and IL-8 production independent of Toll-like
      receptors 2 and 4, receptor for advanced glycation end-products, high-mobility
      group box 1, uric acid, IL-33, or inflammasome activation. IL-1alpha was the key
      IEC-derived necrotic cell product involved in HIF cytokine production. IL-1alpha
      positive cells were identified in the epithelium in human IBD and dextran sulfate
      sodium (DSS)-induced colitis. IL-1alpha was detected in the stool of colitic mice
      before IL-1beta. IL-1alpha enemas reactivated inflammation after DSS colitis
      recovery, induced IL-1 receptor expression in subepithelial fibroblasts, and
      activated de novo inflammation even in mice without overt colitis, after the
      administration of low-dose DSS. IL-1alpha amplifies gut inflammation by inducing
      cytokine production by mesenchymal cells. IL-1alpha-mediated IEC-fibroblast
      interaction may be involved in amplifying and perpetuating inflammation, even
      without obvious intestinal damage. IL-1alpha may be a target for treating early
      IBD or preventing the reactivation of IBD.

PMID- 25864928
TI  - Management of Polypharmacy in Dialysis Patients.
AB  - Most patients receiving dialysis have other common chronic conditions in addition
      to end-stage renal disease, including hypertension, diabetes, cardiovascular
      disease, and mineral and bone disorder, all of which require long-term medication
      management. Dialysis patients take an average of 10-12 prescribed and over-the
      counter medications from an average of 4.7 prescribers, and an average of 19
      pills per day. Thus, reducing polypharmacy is not adequate as a medication
      therapy goal for these patients. Instead, the dialysis community should focus on
      ensuring that all patients receive medications that are appropriate, effective,
      safe and convenient. Barriers to this include a fragmented health care system
      with inadequate communication between multiple prescribers and pharmacies, and
      frequent care transitions between ambulatory care sites (dialysis centre,
      ambulatory primary care practice, ambulatory specialty practice) and the
      hospital, skilled nursing facility or long-term care facility. Three distinct
      processes are necessary to prevent and solve the resultant medication-related
      problems (and reduce polypharmacy). These are medication reconciliation (creating
      an accurate medication list that reflects all medications the patients is taking
      and how they are being taken), medication review (evaluating the list for
      appropriateness, effectiveness, safety and convenience in conjunction with the
      patient's health status), and ongoing patient-centred medication therapy
      management (e.g., developing treatment plans centred on each patient's medication
      related goals). A team approach including pharmacists as part of the dialysis
      team with the dialysis facility as the primary medication home is needed. 

PMID- 25864930
TI  - Nerve regeneration: Specific metabolic demands?

PMID- 25864929
TI  - Interictal spike frequency varies with ovarian cycle stage in a rat model of
      epilepsy.
AB  - In catamenial epilepsy, seizures exhibit a cyclic pattern that parallels the
      menstrual cycle. Many studies suggest that catamenial seizures are caused by
      fluctuations in gonadal hormones during the menstrual cycle, but this has been
      difficult to study in rodent models of epilepsy because the ovarian cycle in
      rodents, called the estrous cycle, is disrupted by severe seizures. Thus, when
      epilepsy is severe, estrous cycles become irregular or stop. Therefore, we
      modified kainic acid (KA)- and pilocarpine-induced status epilepticus (SE) models
      of epilepsy so that seizures were rare for the first months after SE, and
      conducted video-EEG during this time. The results showed that interictal spikes
      (IIS) occurred intermittently. All rats with regular 4-day estrous cycles had IIS
      that waxed and waned with the estrous cycle. The association between the estrous
      cycle and IIS was strong: if the estrous cycles became irregular transiently, IIS
      frequency also became irregular, and when the estrous cycle resumed its 4-day
      pattern, IIS frequency did also. Furthermore, when rats were ovariectomized, or
      males were recorded, IIS frequency did not show a 4-day pattern. Systemic
      administration of an estrogen receptor antagonist stopped the estrous cycle
      transiently, accompanied by transient irregularity of the IIS pattern. Eventually
      all animals developed severe, frequent seizures and at that time both the estrous
      cycle and the IIS became irregular. We conclude that the estrous cycle entrains
      IIS in the modified KA and pilocarpine SE models of epilepsy. The data suggest
      that the ovarian cycle influences more aspects of epilepsy than seizure
      susceptibility. 

PMID- 25864932
TI  - Are overweight/obese children at risk of traumatic dental injuries? A meta
      analysis of observational studies.
AB  - BACKGROUND/AIM: Observational studies which investigated the association between
      overweight/obesity and traumatic dental injuries (TDI) reported contrasting
      results. Thus, this meta-analysis was designed to investigate such an association
      with the highest possible levels of internal and external validities. MATERIAL
      AND METHODS: A comprehensive literature search was performed through PubMed, ISI
      Web of Science, Cochrane Library, Scopus, Google scholar to ensure
      generalizability. Eligible studies reported clear case and control definitions,
      exposure assessment. Where possible, odds ratio (OR) adjusted for covariates was
      extracted. Study quality was assessed through Newcastle-Ottawa Scale (NOS). Only
      fair-to-good quality studies with NOS scores >=4 were selected. The method to
      assess the pooled OR was based on the level of between-study heterogeneity,
      estimated through the Cochran's Q. Reliability of the pooled OR was improved by
      controlling for publication bias, sensitivity analysis to study inclusion, and
      subgroup analyses according to tooth type (permanent vs primary teeth) and
      country where the study was performed (Brazilian studies vs studies from other
      countries). RESULTS: Seventeen studies were selected from America, Asia, and
      Europe, their NOS scores ranged between 4 and 8. Overall, there were almost
      28,000 patients, 7400 of them with TDI. The level of publication bias was
      minimal, and no adjustment was necessary. Between-study heterogeneity was high,
      and the random-effects method was used to assess the pooled OR, which resulted
      1.30 (95% confidence interval, 1.11-1.53; P < 0.05). Sensitivity and subgroup
      analyses corroborated this estimate. CONCLUSION: The choice to increase internal
      and external validity levels decreased the precision of the pooled OR (i.e.,
      confidence intervals were relatively wide). The statistically significant
      overweight/obesity-TDI association, together with the so-called counterfactual
      condition (i.e., TDI prevalence was higher among overweight/obese children than
      among lean children), suggests that causal association between these two
      conditions is plausible.

PMID- 25864931
TI  - Enhanced expression of matrix metalloproteinase-12 contributes to Npc1 deficiency
      induced axonal degeneration.
AB  - Niemann-Pick type C (NPC) disease is a genetic disorder associated with
      intracellular cholesterol accumulation in the brain and other organs, and
      neurodegeneration is generally believed to be the fatal cause of the disease. In
      view of the emerging role of matrix metalloproteinase-12 (MMP-12) in neuronal
      injury, we investigated its expression and potential roles in axonal degeneration
      in Npc1-/- mouse brain. Microarray and quantitative real-time reversed
      transcription PCR analysis indicated a marked increase in MMP-12 mRNA levels in
      cerebellum of 3 week-old Npc1-/- mice, as compared to wild-type littermates.
      Western blots showed that the ratio of mature MMP-12 over pro-MMP-12 was
      significantly increased in cerebellum of Npc1-/-, as compared to wild-type mice.
      Immunohistochemical studies confirmed that MMP-12 expression was increased,
      especially in the cell bodies of Purkinje neurons in Npc1-/- mice. Neuritic
      growth was significantly reduced by Npc1 siRNA knockdown in nerve growth factor
      differentiated PC-12 cells, and this effect was completely reversed by treatment
      with an MMP-12 specific inhibitor. Furthermore, in vivo experiments showed that
      chronic treatment with the MMP-12 inhibitor ameliorated Npc1 deficiency-induced
      axonal pathology in the striatum. Our results indicate that abnormal neuronal
      expression of MMP-12 may contribute to axonal degeneration in NPC disease, thus
      providing a potential novel target for treatment.

PMID- 25864933
TI  - Consumers' health risk-benefit perception of seafood and attitude toward the
      marine environment: Insights from five European countries.
AB  - This research classifies European consumers into segments based on their health
      risk-benefit perception related to seafood consumption. The profiling variables
      of these segments are seafood consumption frequency, general attitude toward
      consuming fish, confidence in control organizations, attitude toward the marine
      environment, environmental concern and socio-demographics. A web-based survey was
      performed in one western European country (Belgium), one northern European
      country (Ireland) and three southern European countries (Italy, Portugal and
      Spain), resulting in a total sample of 2824 participants. A cluster analysis was
      performed based on risk-benefit perception related to seafood and the profiles of
      the segments were determined by a robust 2-way ANOVA analysis accounting for
      country effects. Although this study confirms consumers' positive image of
      consuming seafood, gradients are found in health risk-benefit perception related
      to seafood consumption. Seafood consumption frequency is mainly determined by
      country-related traditions and habits related to seafood rather than by risk
      benefit perceptions. Segments with a higher benefit perception, irrespective of
      their level of risk perception, show a more positive attitude toward consuming
      seafood and toward the marine environment; moreover, they report a higher concern
      about the marine environment and have a higher involvement with seafood and with
      the marine environment. Consequently, information campaigns concentrating on pro
      environmental behavior are recommended to raise the involvement with seafood and
      the marine environment as this is associated with a higher environmental concern.
      This research underpins that in such information campaigns a nationally
      differentiated rather than a pan-European or international information strategy
      should be aimed for because of significant cultural differences between the
      identified segments. 

PMID- 25864934
TI  - Development of a non-infectious encapsidated positive control RNA for molecular
      assays to detect foot-and-mouth disease virus.
AB  - Positive controls are an important component of the quality-control of molecular
      tests used for diagnosis of livestock diseases. For high consequence agents such
      as foot-and-mouth disease virus (FMDV), the positive controls required to monitor
      template extraction, reverse transcription and amplification steps usually
      consist of material derived from infectious viruses. Therefore, their production
      is dependent upon the use of high containment facilities and their deployment
      carries the risks associated with inactivation of "live" FMDV. This paper
      describes the development of a novel non-infectious positive control that encodes
      FMDV RNA sequences that are encapsidated within Cowpea mosaic virus (CPMV)
      particles. This surrogate RNA has been engineered to contain sequences from the
      5'UTR and 3D regions of FMDV targeted by many molecular assays (conventional RT
      PCR, real-time RT-PCR and RT-LAMP). These sequences were inserted into a movement
      deficient version of CPMV RNA-2 which is rescued from cowpea plants (Vigna
      unguiculota) by inoculation with RNA-1. In order to evaluate the performance of
      these encapsidated RNAs, nucleic acid prepared from a 10-fold dilution series was
      tested using a range of molecular assays. Results generated by using the
      molecular assays confirmed RNA-dependent amplification and the suitability of
      these particles for use in a range of diagnostic tests. Moreover, these CPMV
      particles were highly stable for periods of up to 46 days at room temperature and
      37  degrees C. Recombinant CPMV can be used to produce high yields of
      encapsidated RNAs that can be used as positive and negative controls and
      standards in molecular assays. This approach provides a surrogate that can be
      potentially used outside of containment laboratories as an alternative to
      inactivated infectious virus for molecular diagnostic testing.

PMID- 25864935
TI  - Graphene and hydroxyapatite self-assemble into homogeneous, free standing
      nanocomposite hydrogels for bone tissue engineering.
AB  - Graphene-nanoparticle (NP) composites have shown potential in applications
      ranging from batteries to, more recently, tissue engineering. Graphene and NPs
      should be integrated into uniform free-standing structures for best results.
      However, to date, this has been achieved only in few examples; in most cases,
      graphene/NP powders lacking three-dimensional (3D) structure were produced. Here
      we report a facile and universal method that can be used to synthesize such
      structures based on colloidal chemistry. We start from aqueous suspensions of
      both graphene oxide nanosheets and citrate-stabilized hydroxyapatite (HA) NPs.
      Hydrothermal treatment of the mixtures of both suspensions reduces graphene oxide
      to graphene, and entraps colloidal HA NPs into the 3D graphene network thanks to
      a self-assembled graphite-like shell formed around it. Dialysis through this
      shell causes uniform NP deposition onto the graphene walls. The resulting
      graphene-HA gels are highly porous, strong, electrically conductive and
      biocompatible, making them promising scaffolds for bone tissue engineering. This
      method can be applied to produce a variety of free-standing 3D graphene-based
      nanocomposites with unprecedented homogeneity. 

PMID- 25864936
TI  - An approach to improve kernel-based Protein-Protein Interaction extraction by
      learning from large-scale network data.
AB  - Protein-Protein Interaction extraction (PPIe) from biomedical literatures is an
      important task in biomedical text mining and has achieved desirable results on
      the annotated datasets. However, the traditional machine learning methods on PPIe
      suffer badly from vocabulary gap and data sparseness, which weakens
      classification performance. In this work, an approach capturing external
      information from the web-based data is introduced to address these problems and
      boost the existing methods. The approach involves three kinds of word
      representation techniques: distributed representation, vector clustering and
      Brown clusters. Experimental results show that our method outperforms the state
      of-the-art methods on five publicly available corpora. Our code and data are
      available at: http://chaoslog.com/improving-kernel-based-protein-protein
      interaction-extraction-by-unsupervised-word-representation-codes-and-data.html. 

PMID- 25864937
TI  - Risk factors for work-related stress and subjective hardship in health-care staff
      in nursing homes for the elderly: A cross-sectional study.
AB  - OBJECTIVES: This study aimed to explore potential risk factors for work-related
      stress by, detailing working conditions and subjective hardship according to
      occupational category in health-care staff working with elderly patients.
      METHODS: A cross-sectional descriptive survey was conducted in 105 nursing homes
      for the elderly in France. Data on nursing home working conditions were collected
      by occupational physicians. The study population was limited to those in direct
      contact with the elderly, who were divided into 3 occupational groups defined by
      qualifications and tasks: housekeepers (HKs), nursing assistants (NAs) and nurses
      (Ns). Employees answered a questionnaire on their perceived working conditions
      and vocational training courses. Psychosocial stress was assessed with the
      Siegrist questionnaire. RESULTS: The subjects included 706 HKs, 1,565 NAs and 378
      Ns, and the findings showed confusion of tasks and responsibilities in the study
      population. Verbal abuse by residents was reported by 60.9% of HKs (versus 76.2%
      of NAs and 76.7% of Ns, p<0.001). Physical attack by residents was more
      frequently reported by NAs (59.1%) than Ns (52.8%) or HKs (38.0%) (p<0.001).
      Nearly 10% of employees reported clear effort/reward imbalance (10.4% of NAs,
      9.2% of Ns and 7.0% of HKs, p=0.059). Great hardship related to proximity to
      death was reported by 40.5% of HKs (versus 37.3% of NAs and 22.6% of Ns;
      p<0.001). CONCLUSIONS: To prevent stress related to insufficient ability, nursing
      home workers should be encouraged to attend job training courses, which should
      cover knowledge of the specific care needs of elderly patients and of the
      authority/responsibility required to do their job.

PMID- 25864938
TI  - Economic impact of corporate wellness programs in Europe: A literature review.
AB  - OBJECTIVES: The purpose of this review is to summarize the current evidence on
      the economic impact of corporate wellness programs (CWPs) in Europe from the
      results of randomized controlled trials (RCTs) published up to 2013. METHODS: A
      review was undertaken by searching for RCTs with key words in the following
      databases: PubMed, SPORT-Discus, and Business Source Premier. Only RCTs that
      evaluated the economic impact of CWPs, and included analyses performed in Europe
      with results converted into monetary values, were eligible for inclusion. An
      approach to economic analyses from both an employer's perspective and a societal
      perspective was also undertaken. RESULTS: Eleven RCTs were identified, and review
      of these studies determined that the economic impact of the majority of CWPs
      analyzed was mostly negative. We discuss a possible explanation for these
      discrepancies with regard to prior reviews in this area. Despite the fact that
      the RCT is the "gold standard" for investigating without bias, several
      limitations to the methodology may have influenced the results of the studies in
      this review and suggested the use of caution in the interpretation of the
      results. CONCLUSIONS: The findings of this review could be a "wake up call" for
      companies regarding the high probability of bias from non-RCT studies, the
      majority of which report a positive economic impact of these programs, and the
      risk of taking inappropriate decisions based on the results of such studies.

PMID- 25864939
TI  - Acute fluoxetine modulates emotional processing in young adult volunteers.
AB  - BACKGROUND: Fluoxetine is generally regarded as the first-line pharmacological
      treatment for young people, as it is believed to show a more favourable
      benefit:risk ratio than other antidepressants. However, the mechanisms through
      which fluoxetine influences symptoms in youth have been little investigated. This
      study examined whether acute administration of fluoxetine in a sample of young
      healthy adults altered the processing of affective information, including
      positive, sad and anger cues. METHOD: A total of 35 male and female volunteers
      aged between 18 and 21 years old were randomized to receive a single 20 mg dose
      of fluoxetine or placebo. At 6 h after administration, participants completed a
      facial expression recognition task, an emotion-potentiated startle task, an
      attentional dot-probe task and the Rapid Serial Visual Presentation. Subjective
      ratings of mood, anxiety and side effects were also taken pre- and post
      fluoxetine/placebo administration. RESULTS: Relative to placebo-treated
      participants, participants receiving fluoxetine were less accurate at identifying
      anger and sadness and did not show the emotion-potentiated startle effect. There
      were no overall significant effects of fluoxetine on subjective ratings of mood.
      CONCLUSIONS: Fluoxetine can modulate emotional processing after a single dose in
      young adults. This pattern of effects suggests a potential cognitive mechanism
      for the greater benefit:risk ratio of fluoxetine in adolescent patients.

PMID- 25864941
TI  - Using expert informed GIS to locate important marine social-ecological hotspots.
AB  - The marine environment provides significant benefits to many local communities.
      Pressure to develop coastal waterways worldwide creates an urgent need for tools
      to locate marine spaces that have important social or ecological values, and to
      quantify their relative importance. The primary objective of this study was to
      develop, apply and critically assess a tool to identify important social
      ecological hotspots in the marine environment. The study was conducted in a
      typical coastal community in northern British Columbia, Canada. This expert
      informed GIS, or xGIS, tool used a survey instrument to draw on the knowledge of
      local experts from a range of backgrounds with respect to a series of 12 social
      ecological value attributes, such as biodiversity, cultural and economic values.
      We identified approximately 1500 polygons on marine maps and assigned relative
      values to them using a token distribution exercise. A series of spatial
      statistical analyses were performed to locate and quantify the relative social
      ecological importance of marine spaces and the results were ultimately summarized
      in a single hotspot map of the entire study area. This study demonstrates the
      utility of xGIS as a useful tool for stakeholders and environmental managers
      engaged in the planning and management of marine resources at the local and
      regional levels. 

PMID- 25864940
TI  - Treatment of paroxysmal dyskinesias in children.
AB  - OPINION STATEMENT: Paroxysmal dyskinesia represents a group of uncommon movement
      disorders that are characterized by episodes of abnormal movements arising from a
      baseline of normal or nearly normal movement. Recent advances in the genetics of
      these disorders have helped provide some unification of classification schemes
      and better understanding. However, the approach to treatment continues to be
      based on the phenotype more than the genotype. The treatment approach is
      primarily based on the factors that precipitate the episodes of abnormal
      movements. For paroxysmal kinesigenic dyskinesia (PKD) in which the spells are
      triggered by sudden movement, treatment with anticonvulsants that target voltage
      sensitive sodium channels (e.g., carbamazepine or phenytoin) is highly effective.
      For paroxysmal nonkinesigenic dyskinesia (PNKD), treatment with benzodiazepines
      is effective in many patients. PNKD episodes are often precipitated by caffeine,
      ethanol, or sleep deprivation, and lifestyle modifications are often helpful.
      Paroxysmal exertion-induced dyskinesia (PED) is less likely to respond to
      medications, but the ketogenic diet or modified Atkins diet may provide benefit.
      As more knowledge is gained about the underlying biology of these disorders,
      additional treatments may emerge.

PMID- 25864942
TI  - Switching from an anti-TNF monoclonal antibody to soluble TNF-receptor yields
      better results than vice versa: An observational retrospective study of 72
      rheumatoid arthritis switchers.
AB  - OBJECTIVES: To evaluate the benefits for rheumatoid arthritis (RA) patients of
      switching from one tumor necrosis factor inhibitor (TNFi) to another based on
      reason for change (primary failure, escape or intolerance) and molecule-switching
      order. METHODS: Between 2000 and 2008, 356 RA patients prescribed a TNFi
      (infliximab [IFX], etanercept [ETA] or adalimumab [ADA]) and undergoing
      standardized evaluation were included in this retrospective study. Detailed
      demographic, clinical and biological data were collected before first biologic
      use and <=6 months later to evaluate response based on EULAR-criteria. Primary
      failure, escape or intolerance of first TNFi triggered switch to another TNFi,
      the response of which was evaluated 6 months later. Propensity score then
      measured any interaction with baseline variables. RESULTS: Of the 356 RA
      patients, 38 switched from IFX/ADA to ETA, 26 from ETA to IFX/ADA, and eight from
      one monoclonal antibody (mAb; IFX/ADA) to another. Clinical parameters for
      switchers and non-switchers were comparable. Switchers changed therapies because
      of primary failure (36.1%), escape (33.3%), or intolerance (30.6%), with no
      difference found in these subgroups. More switchers responded to the second TNFi
      than the first (P<0.01), respectively, regardless of switch (ETA to IFX/ADA: 50
      vs. 23.1% [P<0.05]; IFX/ADA to ETA: 57.9 vs. 15.8% [P<0.001]) or reason for
      changing. In addition, DAS28 decreased more with the second antagonist (P<0.001)
      and regardless of molecules switched (P<0.01). Survival of the second TNFi was
      significantly longer with switch from mAb to the soluble receptor than vice versa
      (P<0.05). DISCUSSION: Overall, any switching from one TNFi to another, especially
      mAb to soluble receptor, was often beneficial for RA patients.

PMID- 25864943
TI  - Encouraging intrinsic motivation in the clinical setting: teachers' perspectives
      from the self-determination theory.
AB  - INTRODUCTION: Self-determination theory postulates that the three basic
      psychological needs of autonomy, competence and relatedness have to be satisfied
      for students to achieve intrinsic motivation and internalisation of autonomous
      self-regulation towards academic activities. Consequently, the influence of the
      clinical teaching environment becomes crucial when satisfying these needs,
      particularly when promoting or diminishing students' intrinsic motivation. The
      aim of this study was to describe and understand how clinical teachers encourage
      intrinsic motivation in undergraduate dental students based on the three basic
      psychological needs described by the self-determination theory. METHODS: A
      qualitative case study approach was adopted, and data were collected through
      semistructured interviews with nine experienced undergraduate clinical teachers
      of one dental school in Santiago, Chile. Interview transcripts were analysed by
      two independent reviewers using a general inductive approach. FINDINGS: Several
      themes emerged outlining teaching strategies and behaviours. These themes
      included the control of external motivators; gradual transference of
      responsibility; identification and encouragement of personal interests; timely
      and constructive feedback; delivery of a vicarious learning experience; teamwork,
      team discussion, and presence of a safe environment, amongst others. Overall,
      teachers stressed the relevance of empowering, supporting and building a
      horizontal relationship with students. CONCLUSIONS: Our findings regarding dental
      education expand on the research outcomes from other health professions about how
      teachers may support students to internalise behaviours. An autonomy-supportive
      environment may lead students to value and engage in academic activities and
      eventually foster the use of an autonomy-supportive style to motivate their
      patients.

PMID- 25864944
TI  - Introduction of a metabolic joint asymmetry score derived from conventional bone
      scintigraphy. A new tool to differentiate psoriatic from rheumatoid arthritis.
AB  - AIM: Clinical differentiation of psoriatic arthritis (PsA) and rheumatoid
      arthritis (rA) based on the pattern of joint involvement can be difficult; the
      frequent form of PsA with polyarthritis of the peripheral joints may sometime
      resemble rA. We investigated a metabolic joint asymmetry score (MJAS), reflecting
      the overall asymmetric joint involvement on conventional bone scintigraphy, for
      differentiating PsA from rA in patients presenting with peripheral polyarthritis.
      PATIENTS, METHODS: 106 patients (n = 61, PsA; n = 45, rA) with peripheral
      polyarthritis (>= 5 joints) as well as 26 control subjects with no history of
      chronic joint disorders were analyzed. The intensity of articular 99mTc-MDP
      uptake in 40 peripheral joint pairs was scored regarding the bilateral difference
      of each joint based on a scale of 0-2 (no significant, moderate, and marked
      asymmetry, respectively). The patient's MJAS was defined as the sum of uptake
      difference scores of all joint pairs. The association of MJAS with the underlying
      condition (Psoriasis criteria, Revised Criteria of the ACR) was examined.
      RESULTS: 5280 peripheral joint pairs were investigated. There was no significant
      difference in the total number of involved joints in PsA 15.0 +/- 8.2 versus rA
      17.5 +/- 8.8 patients (p = 0.132), but significantly less involvement in the
      control group (6.7 +/- 5.0, p < 0.001). MJAS was markedly higher in PsA (17.0 +/-
      9.6) than in rA (4.8 +/- 3.9, p < 0.001), and correlated with the total number of
      involved joints in PsA (r = 0.516, p < 0.001), but not in rA (r = 0.078, p =
      0.380). The MJAS disparity between PsA and rA persisted after exclusion of the
      DIP joints (14.4 +/- 7.7 vs. 4.4 +/- 3.3; p<0.001). CONCLUSIONS: The new
      reproducible semi-quantification method for the asymmetry of metabolic joint
      involvement permits differentiation of psoriatic from rheumatoid peripheral
      arthritis with MJAS being markedly higher in patients with PsA as compared to rA
      patients. The score may offer an effective complementary tool for characterizing
      patients with peripheral polyarthritis.

PMID- 25864947
TI  - Cubic anatase TiO2 nanocrystals with enhanced photocatalytic CO2 reduction
      activity.
AB  - Single-crystalline anatase TiO2 nanocubes with exposed {100} and {001} facets,
      prepared by hydrothermal and calcination methods, display especially high
      photocatalytic activity toward CO2 reduction to methane and methanol, due to the
      synergistic effects of better crystallization, a more negative conduction band
      position and co-exposed {100} and {001} facets. 

PMID- 25864945
TI  - Diabetes and the risk of infections with immunomodulator therapy in inflammatory
      bowel diseases.
AB  - BACKGROUND: Infections are an important concern in patients using
      immunosuppressive therapy for their inflammatory bowel disease (IBD). Diabetes
      affects nearly 10% of Americans. Whether it confers an additional risk with
      immunosuppression in IBD has not been examined previously. AIM: To examine the
      association between diabetes and infections with immunomodulator use in IBD
      METHODS: Using a validated, multi-institutional IBD cohort, we identified all
      patients who received at least one prescription for immunomodulators
      (thiopurines, methotrexate). Our primary outcome was infection within 1 year of
      the prescription of the immunomodulator. Multivariable logistic regression
      adjusting for relevant confounders was used to estimate the independent
      association with diabetes. RESULTS: Our study included 2766 patients receiving at
      least one prescription for immunomodulators among whom 210 (8%) developed an
      infection within 1 year. Patients who developed an infection were likely to be
      older, have more comorbidities, more likely to have received a prescription for
      steroids but similar in initiation of anti-TNF therapy within that year. Only 8%
      of those without an infection had diabetes compared to 19% of those who developed
      an infection within 1 year [odds ratio (OR) 2.74, 95% confidence interval (CI)
      1.88-3.98, P < 0.001]. On multivariate analysis, diabetes was independently
      associated with a nearly two-fold increase in risk of infections (OR: 1.80, 95%
      CI: 1.20-2.68). There was no increase in risk of infections with addition of anti
      TNF therapy (OR: 1.14, 95% CI: 0.80-1.63). CONCLUSION: Diabetes is an independent
      risk factor for infection in IBD patients using immunomodulator therapy.

PMID- 25864946
TI  - Regulation of systemic energy homeostasis by serotonin in adipose tissues.
AB  - Central serotonin (5-HT) is an anorexigenic neurotransmitter in the brain.
      However, accumulating evidence suggests peripheral 5-HT may affect organismal
      energy homeostasis. Here we show 5-HT regulates white and brown adipose tissue
      function. Pharmacological inhibition of 5-HT synthesis leads to inhibition of
      lipogenesis in epididymal white adipose tissue (WAT), induction of browning in
      inguinal WAT and activation of adaptive thermogenesis in brown adipose tissue
      (BAT). Mice with inducible Tph1 KO in adipose tissues exhibit a similar phenotype
      as mice in which 5-HT synthesis is inhibited pharmacologically, suggesting 5-HT
      has localized effects on adipose tissues. In addition, Htr3a KO mice exhibit
      increased energy expenditure and reduced weight gain when fed a high-fat diet.
      Treatment with an Htr2a antagonist reduces lipid accumulation in 3T3-L1
      adipocytes. These data suggest important roles for adipocyte-derived 5-HT in
      controlling energy homeostasis. 

PMID- 25864948
TI  - The influence of ruthenium on vascular tone.
AB  - OBJECTIVES: Over the past few years, ruthenium has been under attention for
      development of organometallic drugs with various therapeutic applications.
      Because of its favourable characteristics, ruthenium is perfectly suitable for
      drug design. Ruthenium-containing complexes exert a wide range of biological
      effects. However, so far, the influence of ruthenium itself on vascular tone has
      never been studied. METHODS: The effect of ruthenium was analysed through organ
      bath studies measuring isometric tension on mice thoracic aorta. After obtaining
      a stable contraction plateau, cumulative concentration-response curves of the
      ruthenium-compounds (RuCl3 , Ruthenium Red, [RuCl2 (CO)3 ]2 and RuCl2 (DMSO)4 )
      (30-600 MUmol/l) were performed. The effect of RuCl3 after contraction with
      different contractile agents was evaluated. Furthermore, the influence of
      ruthenium-containing molecules on endogenous (acetylcholine) and exogenous
      (sodium nitroprusside) NO-mediated relaxations was determined. KEY FINDINGS: All
      studied ruthenium compounds elicit, to some extent, a decrease of the contraction
      level. Looking further into the underlying mechanism, we found that RuCl3 relaxes
      aortic rings only when contracted with norepinephrine. This RuCl3 -induced
      relaxation can be prevented by the antioxidants ascorbic acid and N-acetyl L
      cysteine. In addition, ruthenium compounds may diminish acetylcholine- or sodium
      nitroprusside-induced relaxations. CONCLUSIONS: Ruthenium-containing molecules
      can influence vascular tone induced by norepinephrine due to oxidative
      inactivation. Moreover, they can undermine NO-mediated responses. This should be
      considered when developing ruthenium-containing drugs.

PMID- 25864949
TI  - A simple construction of electrochemical liver microsomal bioreactor for rapid
      drug metabolism and inhibition assays.
AB  - In order to design a green microsomal bioreactor on suitably identified carbon
      electrodes, it is important to understand the direct electrochemical properties
      at the interfaces between various carbon electrode materials and human liver
      microsomes (HLM). The novelty of this work is on the investigation of directly
      adsorbed HLM on different carbon electrodes with the goal to develop a simple,
      rapid, and new bioanalytical platform of HLM useful for drug metabolism and
      inhibition assays. These novel biointerfaces are designed in this study by a one
      step adsorption of HLM directly onto polished basal plane pyrolytic graphite
      (BPG), edge plane pyrolytic graphite (EPG), glassy carbon (GC), or high-purity
      graphite (HPG) electrodes. The estimated direct electron transfer (ET) rate
      constant of HLM on the smooth GC surface was significantly greater than that of
      the other electrodes. On the other hand, the electroactive surface coverage and
      stability of microsomal films were greater on highly surface defective, rough EPG
      and HPG electrodes compared to the smooth GC and less defective hydrophobic BPG
      surfaces. The presence of significantly higher oxygen functionalities and
      flatness of the GC surface is attributed to favoring faster ET rates of the
      coated layer of thin HLM film compared to other electrodes. The cytochrome P450
      (CYP)-specific bioactivity of the liver microsomal film on the catalytically
      superior, stable HPG surface was confirmed by monitoring the electrocatalytic
      conversion of testosterone to 6beta-hydroxytestosterone and its inhibition by the
      CYP-specific ketoconazole inhibitor. The identification of optimal HPG and EPG
      electrodes to design biologically active interfaces with liver microsomes is
      suggested to have immense significance in the design of one-step, green
      bioreactors for stereoselective drug metabolite synthesis and drug metabolism and
      inhibition assays. 

PMID- 25864950
TI  - Challenging the need for sustained blockade of dopamine D2 receptor estimated
      from antipsychotic plasma levels in the maintenance treatment of schizophrenia: A
      single-blind, randomized, controlled study.
AB  - OBJECTIVE: Blockade of dopamine D2 receptors with antipsychotics above 65% is
      associated with optimal chance of clinical response although recent data suggest
      a lower threshold for the maintenance treatment of schizophrenia. The objective
      of this study was to prospectively examine whether such continuous high blockade
      would be necessary for maintenance treatment. METHOD: In this single-blind, 52
      week, randomized controlled trial, clinically stable patients with schizophrenia
      receiving risperidone or olanzapine were randomly assigned to the continuous D2
      blockade (i.e. an estimated trough D2 blockade of >65%) or non-continuous
      blockade group (i.e. an estimated peak level of >65% with an estimated trough
      level of <65%). Oral doses corresponding to the assigned blockade levels were
      estimated from random plasma drug concentrations, using the models we developed;
      antipsychotic doses were then adjusted accordingly. Psychopathology and side
      effects were assessed at baseline and one year with the Positive and Negative
      Syndrome Scale (PANSS), Simpson-Angus Scale (SAS), and Abnormal Involuntary
      Movement Scale (AIMS). RESULTS: Sixty-eight subjects (34 in each group) were
      enrolled. Twenty-six (76.5%) and thirty-one (91.2%) subjects completed the study
      in the continuous and non-continuous blockade groups, respectively, without any
      significant group difference. No significant differences were found on any of the
      assessment scales between the two groups. The degree of dosage change was small
      in both groups. CONCLUSION: These results offer support that the threshold for D2
      receptor blockade in the maintenance treatment can be lower than 65%. However,
      these preliminary findings have to be confirmed through double-blind, larger
      scale trials with longer follow-up periods.

PMID- 25864951
TI  - Impaired facial emotion recognition in individuals at ultra-high risk for
      psychosis and with first-episode schizophrenia, and their associations with
      neurocognitive deficits and self-reported schizotypy.
AB  - OBJECTIVE: This study aims to quantify facial emotion recognition abnormalities
      and their relation to neurocognitive dysfunction and schizotypy in individuals at
      ultra-high risk (UHR) for psychosis and patients with first-episode schizophrenia
      (FES). METHODS: Forty individuals at UHR for psychosis, 24 patients with FES and
      46 normal controls performed a facial emotion recognition task that presented
      facial photographs encompassing all basic emotions. The perceptual aberration
      scale and revised social anhedonia scale were employed for self-reported
      assessment of schizotypy. An intellectual functioning (IQ) test and a broad
      battery of neurocognitive tests were conducted. Emotional task performance
      indexed by accuracy rate of specific emotion was compared among three groups. The
      correlation of accuracy rate with neurocognitive tests and schizotypy scales were
      analyzed within each clinical group. RESULTS: A recognition deficit of facial
      emotions was present in both clinical groups, even after adjusting for IQ and
      gender as covariates. This emotional deficit showed few significant relationships
      with broad range of individual neurocognitive measures. Meanwhile, this deficit
      demonstrated significant relationships with schizotypy, especially perceptual
      aberration in each clinical group. CONCLUSIONS: Facial emotion recognition
      deficit may not only be present in FES patients, but may already have evolved
      prior to the onset of overt psychotic symptoms. This emotion recognition deficit
      may be linked to a perceptual aberration and largely independent of broad range
      of neurocognitive dysfunction.

PMID- 25864952
TI  - Neural correlates of out-group bias predict social impairment in patients with
      schizophrenia.
AB  - BACKGROUND: Social impairments are a hallmark feature of schizophrenia and are a
      key predictor of functional disability. Deficits in social information processing
      likely underlie social impairment; however, this relationship is understudied. We
      previously demonstrated that patients with schizophrenia fail to habituate to
      neutral faces, providing evidence for an alteration in basic social information
      processing. It remains unknown whether patients with schizophrenia also show
      deficits in processing of more complex social information. Out-group bias
      provides an excellent opportunity to test complex social information processing
      because the bias requires basic face processing skills, the ability to
      discriminate between groups, as well as the ability to categorize oneself into a
      salient social group. METHODS: Study participants were 23 patients with
      schizophrenia and 21 controls. Using functional magnetic resonance imaging,
      habituation of response to 120 s of repeated presentations of faces was assessed
      in participants who viewed either same-gender faces or opposite-gender faces. The
      interaction between face gender (same/opposite) and group was examined in three
      key regions: amygdala, hippocampus, and visual cortex. Social impairment was
      measured using the PANSS and correlations between social impairment and out-group
      effect (main effect of face type) were performed in patients. RESULTS: Patients
      with schizophrenia had aberrant neural responses to opposite-gender faces
      (interaction, p<.05 corrected). Healthy controls showed an immediate heightened
      response to opposite-gender faces relative to same-gender faces; but in patients
      this effect was substantially delayed (~70s). In patients with schizophrenia, the
      out-group bias was significantly correlated with social impairment. Patients with
      no social impairment showed a heightened neural response to opposite-gender faces
      after 30s, whereas patients with mild-moderate social impairment failed to ever
      show a heightened response. CONCLUSION: Alterations in neural responses during
      out-group processing predicted degree of social impairment in patients with
      schizophrenia; thus, neural responses to opposite-gender faces may provide a
      novel measure for studies of treatment response and disease outcome.

PMID- 25864953
TI  - Hippocampal, amygdala and nucleus accumbens volume in first-episode schizophrenia
      patients and individuals at high familial risk: A cross-sectional comparison.
AB  - It is unknown whether brain changes occur prior to onset of schizophrenia or
      after it develops. Prospective familial high risk studies provide a good method
      to investigate this. In the Edinburgh High Risk Study, structural MRI scans of
      150 young individuals at familial high risk of schizophrenia, 34 patients with
      first-episode schizophrenia and 36 matched controls were obtained. Of the high
      risk participants with scans suitable for analysis, 17 developed schizophrenia
      after the scans were taken, whilst 57 experienced isolated or sub-clinical
      psychotic symptoms, and 70 remained well. We used Freesurfer to extract
      volumetric measurements of the hippocampus, amygdala and nucleus accumbens with
      the aim of assessing whether any alterations found were present in all those at
      high risk, or selectively in the high risk cohort based on future clinical
      outcome, or only in those experiencing their first-episode of psychosis. We found
      no significant differences in any examined regions between controls and those at
      high risk, or between those at high risk who later developed schizophrenia and
      those who remained well. However, patients with first-episode schizophrenia
      demonstrated significant volumetric reductions in the bilateral hippocampus, left
      amygdala, and right nucleus accumbens compared to high risk individuals and
      healthy controls, which were not significantly associated with the intake of anti
      psychotic medication or duration of illness. We found that patients had
      significantly smaller left amygdalae and bilateral hippocampus compared to
      HR[ill]. Our findings suggest that volumetric reductions of the hippocampus,
      amygdala and nucleus accumbens occur early in the first-episode of psychosis. The
      apparent absence of high risk versus control differences we found using
      Freesurfer is at odds with our previous studies conducted on the same sample, and
      possible methodological reasons for these apparent discrepancies are discussed. 

PMID- 25864954
TI  - Elevated C-reactive protein is associated with sensory gating deficit in
      schizophrenia.
AB  - Sensory and cognitive impairments and inflammatory processes are contributing
      factors to the pathogenesis of schizophrenia. A previous study found that an
      elevated CRP level (>=5mg/L) was associated with higher cognitive impairments in
      schizophrenia. We aimed to investigate the association between an elevated CRP
      level and sensory impairments defined by a sensory gating deficit (abnormal P50
      suppression) in 55 outpatients. Fifteen patients (27.3%) had an elevated CRP
      level that was associated with higher rate of sensory gating deficit (60% vs.
      12.5%, p<0.001). This is the first study suggesting a relationship between
      sensory gating deficit and inflammatory processes in schizophrenia. 

PMID- 25864955
TI  - Away from home: the brain of the wandering mind as a model for schizophrenia.
AB  - BACKGROUND: The notion that schizophrenia patients' (SZ) sense of being detached
      from external reality is a core feature of the disorder has existed since the
      early days of its recognition and is still largely emphasized in first person
      accounts of SZs; however, its etiology, neurophysiological mechanism, and
      significance for clinical symptoms are unclear. Mind-wandering is a ubiquitous
      experience of being detached from reality, the underlying neural mechanism of
      which closely resembles the brain in a resting-state. METHODS: The resting-state
      functional magnetic resonance imaging data of 33 SZs and 33 matched healthy
      controls (CNT) were acquired. All subjects answered the mind-wandering subscale
      of the Imaginal Processing Inventory Questionnaire. Functional connectivity maps
      were constructed using 82 regions of interest comprising default-mode, salience,
      and frontoparietal networks. RESULTS: SZs exhibit significantly higher mind
      wandering frequency relative to CNT. The elevated mind-wandering frequency in SZs
      significantly correlated with positive and general symptom severity. The mind
      wandering frequency was inversely correlated with connectivity degree in the
      right ventromedial prefrontal cortex, the brain region involved in self
      experience in SZs. CONCLUSIONS: Our results suggest that self-disturbances in SZs
      can explain SZs' disconnection to the external world, leading to the
      manifestation of positive psychotic symptoms. This study demonstrates strong
      preliminary evidence that contributes significantly to resolve the complex
      relationship between self, world, and the brain of SZs, which may lie at the
      "core" of psychotic experiences.

PMID- 25864956
TI  - Toward greener analytical techniques for the absolute quantification of peptides
      in pharmaceutical and biological samples.
AB  - Peptide-based biopharmaceuticals represent one of the fastest growing classes of
      new drug molecules. New reaction types included in the synthesis strategies to
      reduce the rapid metabolism of peptides, along with the availability of new
      formulation and delivery technologies, resulted in an increased marketing of
      peptide drug products. In this regard, the development of analytical methods for
      quantification of peptides in pharmaceutical and biological samples is of utmost
      importance. From the sample preparation step to their analysis by means of
      chromatographic or electrophoretic methods, many difficulties should be tackled
      to analyze them. Recent developments in analytical techniques emphasize more and
      more on the use of green analytical techniques. This review will discuss the
      progresses in and challenges observed during green analytical method development
      for the quantification of peptides in pharmaceutical and biological samples. 

PMID- 25864957
TI  - Side predominance of squamous cell carcinoma: further evidence.

PMID- 25864958
TI  - Effect of different exercise protocols on metabolic profiles and fatty acid
      metabolism in skeletal muscle in high-fat diet-fed rats.
AB  - OBJECTIVE: To evaluate the efficacy of mild-intensity endurance, high-intensity
      interval, and concurrent exercise on preventing high-fat diet-induced obesity.
      METHODS: Male rats were divided into five groups, control diet/sedentary group,
      high-fat diet/sedentary, high-fat diet/endurance exercise, high-fat diet/interval
      exercise (HI), and high-fat diet/concurrent exercise. All exercise groups were
      made to exercise for 10 weeks, with matched running distances. Body weight, fat
      content, blood metabolites, quantitative insulin sensitivity check index
      (QUICKI), and adipocyte and liver lipid droplet size were assessed, and the
      expression of fatty acid metabolism-related genes was quantified. RESULTS: All
      exercise protocols reduced body weight, adiposity, serum triglycerides, and
      fasting glucose and also improved QUICKI to some extent. However, only HI
      prevented obesity and its associated pathologies completely. The expression of
      stearoyl-coenzyme A desaturase-1 was elevated in all rats fed a high-fat diet
      whereas carnitine palmitoyltransferase 1 (CPT1) expression was increased with
      exercise. Rev-erbalpha expression was elevated only in the HI group, which also
      had the highest level of CPT1 expression. CONCLUSIONS: The HI-induced increase in
      Rev-erbalpha and CPT1 expression was associated with the complete prevention of
      diet-induced obesity. Moreover, the increased caloric expenditure achieved with
      this protocol was preferential over other exercise regimens, and might be used to
      improve lipid metabolism.

PMID- 25864959
TI  - Motor neuron-expressed microRNAs 218 and their enhancers are nested within
      introns of Slit2/3 genes.
AB  - miR218-1 and miR218-2 are embedded in introns of SLIT2 and SLIT3, respectively,
      an arrangement conserved throughout vertebrate genomes. Both miR218 genes are
      predicted to be transcribed in the same orientation as their host genes and were
      assumed to be spliced from Slit2/3 primary transcripts. In zebrafish miR218 is
      active in cranial nerve motor nuclei and spinal cord motor neurons, while slit2
      and slit3 are expressed predominantly in the midline. This differential
      expression pattern suggested independent regulation of miR218 genes by distinct
      enhancers. We tested conserved noncoding elements for regulatory activity by
      reporter gene transgenesis in zebrafish. Two human enhancers, 76 kb and 130 kb
      distant from miR218-2, were identified that drove GFP expression in zebrafish in
      an almost complete miR218 expression pattern. In the zebrafish slit3 locus, two
      enhancers with identical activity were discovered. In human SLIT2 one enhancer 52
      kb upstream of miR218-1 drove an expression pattern very similar to the enhancers
      of miR218-2. This establishes that miR218-1/-2 regulatory units are nested within
      SLIT2/3 and that they are duplicates of an ancestral single locus. Due to the
      strong activity of the enhancers, unique transgenic lines were created that
      facilitate morphological and gene functional genetic experiments in motor
      neurons.

PMID- 25864960
TI  - Flexible Solid-State Supercapacitor Based on a Metal-Organic Framework Interwoven
      by Electrochemically-Deposited PANI.
AB  - Metal-organic frameworks (MOFs) have received increasing attention as promising
      electrode materials in supercapacitors (SCs). Yet poor conductivity in most MOFs
      largely thwarts their capacitance and/or rate performance. In this work, an
      effective strategy was developed to reduce the bulk electric resistance of MOFs
      by interweaving MOF crystals with polyaniline (PANI) chains that are
      electrochemically deposited on MOFs. Specifically we synthesized cobalt-based MOF
      crystals (ZIF-67) onto carbon cloth (CC) and further electrically deposited PANI
      to give a flexible conductive porous electrode (noted as PANI-ZIF-67-CC) without
      altering the underlying structure of the MOF. Electrochemical studies showed that
      the PANI-ZIF-67-CC exhibits an extraordinary areal capacitance of 2146 mF cm(-2)
      at 10 mV s(-1). A symmetric flexible solid-state supercapacitor was also
      assembled and tested. This strategy may shed light on designing new MOF-based
      supercapacitors and other electrochemical devices. 

PMID- 25864962
TI  - Patients' Evaluations of Complete Denture Therapy and Their Association with
      Related Variables: A Pilot Study.
AB  - PURPOSE: Patient satisfaction is an important goal in complete denture therapy,
      and many factors influence this parameter. This study aimed to evaluate
      expectations before and satisfaction after therapy with complete dentures. As a
      secondary objective, other variables that may interfere with patient satisfaction
      were also evaluated. MATERIAL AND METHODS: A representative sample of 99 patients
      assigned visual analog scale (VAS) scores to their expectations before and
      satisfaction after therapy regarding chewing, esthetics, comfort, and phonetics.
      Demographic data and answers to a questionnaire concerning the dentists' conduct
      were recorded. Multiple linear regression was used to evaluate the association
      among studied variables and patients' expectation and satisfaction with their
      dentures. RESULTS: The average VAS scores were high for both expectations and
      satisfaction, and satisfaction exceeded expectations. Patients' expectations
      about esthetics and comfort were associated with age and self-reported time of
      using complete dentures. Patient satisfaction regarding chewing was associated
      with the number of postdelivery adjustments. Also, patient satisfaction regarding
      esthetics was associated with gender and esthetic expectations. In regard to
      phonetic satisfaction, associations were verified among self-reported time of
      using complete dentures, comfort and phonetics expectations, and dentists'
      explanations. Comfort satisfaction was associated only with educational level.
      CONCLUSIONS: Patient satisfaction regarding complete dentures exceeded
      expectations and an expressive majority of positive evaluations of the dentists
      was noticed. Many patient-related variables seemed to influence their evaluations
      of their dentures.

PMID- 25864961
TI  - Cortical neuronal activity does not regulate sleep homeostasis.
AB  - The neural substrate of sleep homeostasis is unclear, but both cortical and
      subcortical structures are thought to be involved in sleep regulation. To test
      whether prior neuronal activity in the cortex or in subcortical regions drives
      sleep rebound, we systemically administered atropine (100mg/kg) to rats,
      producing a dissociated state with slow-wave cortical electroencephalogram (EEG)
      but waking behavior (e.g. locomotion). Atropine injections during the light
      period produced 6h of slow-wave cortical EEG but also subcortical arousal.
      Afterward, rats showed a significant increase in non-rapid eye movement (NREM)
      sleep, compared to the same period on a baseline day. Consistent with the
      behavioral and cortical EEG state produced by systemic atropine, c-Fos expression
      was low in the cortex but high in multiple subcortical arousal systems. These
      data suggest that subcortical arousal and behavior are sufficient to drive sleep
      homeostasis, while a sleep-like pattern of cortical activity is not sufficient to
      satisfy sleep homeostasis. 

PMID- 25864963
TI  - Structural hippocampal alterations, perceived stress, and coping deficiencies in
      patients with anorexia nervosa.
AB  - OBJECTIVE: Anorexia nervosa (AN) is a severe mental illness that mainly affects
      young females. Studies have found a reduction of the hippocampus-amygdala
      formation in people with AN, a brain region that is especially vulnerable to
      stress. In addition, patients with AN were found to perceive higher stress levels
      and to have more coping deficiencies than healthy controls. No prior study has
      considered a connection between stress, coping, and the hippocampal volume in AN.
      Therefore, the purpose of our study was to analyze the volume of hippocampal
      substructures, and its relation to stress and coping. METHOD: We tested 21
      females currently affected by AN and 21 age-matched normal controls (NC).
      Demographic and behavioral data were assessed. A magnetic resonance (MR) scanner
      was used to collect data reflecting volume of cortical structures. We performed
      comparisons between groups and calculated correlations between the hippocampal
      volume and coping strategies or stress. RESULTS: The results showed a significant
      reduction of the hippocampal fimbria and a significant enlargement of the
      hippocampal fissure in patients with AN compared to the NC. In addition, patients
      with AN were found to report higher stress levels and to have more coping
      deficiencies than healthy controls. The hippocampal volume showed a trend-level
      association with stress in patients with AN. DISCUSSION: In sum, our study
      provides the first-available evidence that perceived stress in patients with AN
      could be related to hippocampal volume. Our results may contribute to a better
      understanding of the pathophysiology of AN and, therefore, help to improve the
      treatment.

PMID- 25864964
TI  - A simple but precise method for quantitative measurement of the quality of the
      laser focus in a scanning optical microscope.
AB  - We report a method for characterizing the focussing laser beam exiting the
      objective in a laser scanning microscope. This method provides the size of the
      optical focus, the divergence of the beam, the ellipticity and the astigmatism.
      We use a microscopic-scale knife edge in the form of a simple transmission
      electron microscopy grid attached to a glass microscope slide, and a light
      collecting optical fibre and photodiode underneath the specimen. By scanning the
      laser spot from a reflective to a transmitting part of the grid, a beam profile
      in the form of an error function can be obtained and by repeating this with the
      knife edge at different axial positions relative to the beam waist, the
      divergence and astigmatism of the postobjective laser beam can be obtained. The
      measured divergence can be used to quantify how much of the full numerical
      aperture of the lens is used in practice. We present data of the beam radius,
      beam divergence, ellipticity and astigmatism obtained with low (0.15, 0.7) and
      high (1.3) numerical aperture lenses and lasers commonly used in confocal and
      multiphoton laser scanning microscopy. Our knife-edge method has several
      advantages over alternative knife-edge methods used in microscopy including that
      the knife edge is easy to prepare, that the beam can be characterized also
      directly under a cover slip, as necessary to reduce spherical aberrations for
      objectives designed to be used with a cover slip, and it is suitable for use with
      commercial laser scanning microscopes where access to the laser beam can be
      limited. 

PMID- 25864965
TI  - C-H alkenylations with alkenyl acetates, phosphates, carbonates, and carbamates
      by cobalt catalysis at 23  degrees C.
AB  - Inexpensive cobalt catalysts with N-heterocyclic carbene ligands enable direct
      arene alkenylations with easily accessible alkenyl acetates through
      regioselective C-H/C-O functionalizations in a stereoconvergent fashion. The
      versatile cobalt catalyst was broadly applicable and thus also allowed for the
      efficient conversion of alkenyl phosphates, carbonates, and carbamates at ambient
      temperature.

PMID- 25864966
TI  - A field investigation on transport of carbon-supported nanoscale zero-valent iron
      (nZVI) in groundwater.
AB  - The application of nanoscale zero-valent iron (nZVI) for subsurface remediation
      of groundwater contaminants is a promising new technology, which can be
      understood as alternative to the permeable reactive barrier technique using
      granular iron. Dechlorination of organic contaminants by zero-valent iron seems
      promising. Currently, one limitation to widespread deployment is the fast
      agglomeration and sedimentation of nZVI in colloidal suspensions, even more so
      when in soils and sediments, which limits the applicability for the treatment of
      sources and plumes of contamination. Colloid-supported nZVI shows promising
      characteristics to overcome these limitations. Mobility of Carbo-Iron Colloids
      (CIC) - a newly developed composite material based on finely ground activated
      carbon as a carrier for nZVI - was tested in a field application: In this study,
      a horizontal dipole flow field was established between two wells separated by
      5.3m in a confined, natural aquifer. The injection/extraction rate was 500L/h.
      Approximately 1.2kg of CIC was suspended with the polyanionic stabilizer
      carboxymethyl cellulose. The suspension was introduced into the aquifer at the
      injection well. Breakthrough of CIC was observed visually and based on total
      particle and iron concentrations detected in samples from the extraction well.
      Filtration of water samples revealed a particle breakthrough of about 12% of the
      amount introduced. This demonstrates high mobility of CIC particles and we
      suggest that nZVI carried on CIC can be used for contaminant plume remediation by
      in-situ formation of reactive barriers. 

PMID- 25864968
TI  - Trauma in children/adolescents: a special focus on Third World countries.
AB  - This paper presents a literature review on trauma in children/adolescents with a
      specific focus on Third World countries. We reviewed the literature starting from
      1990 to 2003 using electronic bibliographic databases. Results indicate that out
      of the 306 references selected for the review, 32 studies were conducted on
      children/adolescents in African countries compared to 67 studies in Asian
      countries, 61 in Middle Eastern countries, 46 in Latin American countries and 53
      in Eastern European countries. The few promising studies on PTSD (post-traumatic
      stress disorder) in Africa have mostly been conducted in African-English-speaking
      countries, implying a need for research on PTSD in Francophone countries.
      Findings also show that existing literature on African children/adolescents is
      largely focussed on PTSD in relation to stressors such as war and political
      violence. Future research should be extended to include the impact of different
      types of traumatic events such as natural disasters, confinement in refugee
      camps, massive internal displacement, sexual abuse and mass killing on African
      children/adolescents to expand the knowledge base in this area. In addition, more
      work is needed to understand the effects of culture, gender, age and ethnicity on
      trauma in children/adolescents to allow for better provision of health services. 

PMID- 25864969
TI  - The Denver II Scales and the Griffiths Scales of Mental Development: a
      correlational study.
AB  - Screening measures aim to minimise the number of children being diagnosed
      incorrectly; however, many of these measures have been based on the "normal"
      white population. This study identified the need for a valid developmental
      assessment of black preschool children. The general aim of the study was to
      investigate the use of the Denver II and the Griffiths Scales on a pre-school
      black Xhosa-speaking sample. Specifically, the aim was to investigate the
      relationship between the Denver II Scales and the Griffiths Scales, in order to
      provide the first step in establishing the validity of the Denver II Scales on a
      South African black population. A correlational design was used and the sample
      was comprised of 60 Xhosa-speaking children between the ages of 3 and 6 years.
      The findings revealed that there was a significant relationship between the
      overall performance of the Denver II and the Griffiths Scales. However, the
      Personal-Social Scale of the Denver II appeared to have items that were
      culturally biased. Further, the Denver II further identified a higher percentage
      of the sample to have abnormal or questionable protocols than the Griffiths
      Scales did. 

PMID- 25864967
TI  - New insights into the epidemiology of non-Hodgkin lymphoma and implications for
      therapy.
AB  - Non-Hodgkin lymphoma (NHL) comprises numerous biologically and clinically
      heterogeneous subtypes, with limited data examining the risk factors for these
      distinct disease entities. Many limitations exist when studying lymphoma
      epidemiology; therefore, until recently, little was known regarding the etiology
      of NHL subtypes. This review highlights the results of recent pooled analyses
      examining the risk factors for NHL subtypes. We outline the heterogeneity and
      commonality among the risk factors for NHL subtypes, with proposed subtype
      specific as well as shared etiologic mechanisms. In addition, we describe how the
      study of lymphoma epidemiology may translate into prevention or therapeutic
      targeting as we continue to explore the complexities of lifestyle and genetic
      factors that impact lymphomagenesis. 

PMID- 25864970
TI  - Training in child and adolescent psychiatry for primary health care nurses in
      South Africa.
AB  - Objective - To obtain feedback from primary care nurses who attended two study
      days in child and adolescent mental health. The study days aimed to equip nurses
      with basic assessment and intervention skills for the most common problems in
      child and adolescent psychiatric nursing. Method - All 144 and 68 primary care
      nurses who attended Study Days 1 and 2 respectively completed confidential
      questionnaires after each day. Key findings - Over 80% of the nurses practised in
      settings in which one would expect to encounter children or adolescents suffering
      from, or at risk for, mental health problems. Weekly contact with youngsters with
      mental health problems was reported by 61.1% of the nurses. The majority of
      nurses (77.8%) reported consulting with other professionals when managing these
      problems. Important barriers to child and adolescent mental health services
      provision at primary care level included busy clinics, training deficits and time
      management. Only 2.8% reported that lack of interest was a barrier. There was an
      overwhelmingly positive response to both study days. The nurses were able to
      apply what they had learned between the study days. Almost half usually spent at
      least 30 minutes on counselling when managing children or adolescents with mental
      health problems. Many unmet needs for further training, consultation and
      supervision were identified. Conclusions - The next challenge is to investigate
      whether such study days result in more positive outcomes for children and
      adolescents with mental health problems and their families. 

PMID- 25864971
TI  - A broader perspective on childhood maltreatment and mental health care.
AB  - Objective - The data collection began as a clinical audit for service monitoring
      and development purposes. However, what emerged showed major areas of deficit in
      society's response to children and their needs. Method - Clinical records were
      retrospectively examined for attenders at a child mental health outpatient
      facility in Pietermaritzburg over a one-year period. Demographic and clinical
      variables were recorded and analysed, using descriptive statistics. Results - Of
      the 143 attenders, 40.8% of the girls had recent histories of sexual abuse, of
      whom family or friends abused 82.6%. Children from fractured families constituted
      72% of the attenders. Almost 70% of the children spoke isiZulu as a first
      language, although extremely few psychologists and psychiatrists speak isiZulu.
      Almost one-third of the children traveled distances up to 200km to access this
      mental health resource. Conclusions - Clearly sexual abuse and the breakdown of
      family life appear to be significantly implicated in child mental health
      referrals in the region, pointing to the dire need for preventive efforts. The
      mental health system must ensure that practitioners are able to communicate with
      their patients in their home languages to ensure high quality care. It is
      essential that mental health services be widened beyond the metropolitan areas,
      in order to improve access by rural communities. 

PMID- 25864972
TI  - Evaluation of HIV/AIDS prevention intervention messages on a rural sam- ple of
      South African youth's knowledge, attitudes, beliefs and behaviours over a period
      of 15 months.
AB  - The aim of this study is to evaluate HIV/AIDS prevention intervention messages in
      a large rural youth population (15-24 years) in South Africa over a period of 15
      months. A representative community sample of 421 youth at time one and 416 at
      time two participated in the study using a three-stage cluster sampling method
      for a household survey. Results show that over a period of 15 months sexual risk
      behaviour reduced (multiple partners) and the number of sexually transmitted
      symptoms reduced. Attitudes towards persons living with HIV/AIDS improved partly
      due to mass media and to a lesser extent through community interventions and
      partly determined by the high level of mortality experienced in the studied
      communities. Peer educators had a significant impact on HIV/AIDS knowledge and
      favourable attitude towards people living with HIV/AIDS, magazines on lower HIV
      risk behaviour and exposure to HIV/AIDS radio messages on consistent condom use.
      In this African sample of youth the reduction of sexual partners seem to be more
      feasible than (consistent) condom use to prevent STD and HIV infection. 

PMID- 25864973
TI  - Linking theory and technique in a systems approach to learning problems in
      disadvantaged children.
AB  - The paper describes a programme for disadvantaged children with learning problems
      (due to factors other than cognitive deficits), at the University of Cape Town
      (UCT) Child Guidance Clinic, developed in the absence of subsidised services for
      children in need of remediation of scholastic skills. In collaboration with
      teacher trainees from the Cape Technikon, the programme intervenes on a cognitive
      and an emotional level. The learning problem is conceptualised in the context of
      the dysfunctional systems in which the children have been raised - the post
      apartheid socio-cultural environment, the family and the school. The paper
      illustrates the complexities in working with learning problems and focuses on the
      emotional aspects of the problem in particular. It highlights the importance of
      the development of the capacity to self regulate, and the containment of feelings
      in all the systems involved - the family, the school and the staff in the
      program. The aim is to further each child's ability to learn, in relation to his
      potential. 

PMID- 25864974
TI  - Challenges facing psychologists in a child psychology clinic in South Africa.
AB  - Working in a child psychology clinic is a constant reminder to staff that
      psychological practice and expectations regarding interventions require
      modification in our South African context. Using a case study, the author
      reflects on the way in which any meaningful psychological intervention needs to
      take a broad view of the role of the psychologist/mental health worker. Although
      intervention at the individual level may be beneficial, the lack of supporting
      structures and poor access to educational, social and health facilities for most
      children presenting at the clinic may detract from the impact of psychological
      therapy. The paper suggests some of the ways in which psychological intervention
      can begin to address this issue. 

PMID- 25864976
TI  - Sexual abuse of young children in southern Africa.

PMID- 25864975
TI  - Qualitative adolescent health research - focus groups: a rural South African
      example.
AB  - This paper introduces nine steps that are recommended in conducting focus group
      discussions in rural communities and gives an example of how they can
      appropriately and fruitfully be employed in adolescent health behavioural
      research. The paper also reviewed issues related to methods of data collection,
      data analysis, reliability and validity in qualitative research. Focus group
      discussions took place in classrooms in three schools in Mankweng, Limpopo
      Province of South Africa. Three groups (boys only, girls only and mixed) took
      part in each school. Participants were selected from the pool of standard seven
      (grade 9) students from the chosen schools. The nine steps that were involved in
      using focus group discussions as a research method and the Mankweng experience is
      discussed. These steps include: (1) conducting a social influence analysis; (2)
      identifying the specific information to collect; (3) designing focus group
      discussion guide; (4) choosing the participants for the focus group discussion;
      (5) selecting focus group discussion moderators; (6) training focus group
      discussion moderators; (7) conducting the focus group discussion; (8) analysing
      the data collected; (9) formulating study conclusions and policy recommendations.
      Little adolescent health research in South Africa has been based upon methods
      that can capture the complexity of the role of significant others in adolescent
      health and development and the powerlessness of rural communities in dealing with
      the 'new morbidity' of adolescent risk behaviours. Understanding what sort of
      power relations, for example, that are involved in being relatively disadvantaged
      and how the power of such social groups can be increased is common concern of
      development managers and other individuals and institutions engaged in policy
      changes and implementation and deserve to be an essential component of child and
      adolescent health research. Well-collected and well-analysed qualitative data is
      needed in order to clearly understand some of the underlying predisposing,
      enabling and reinforcing factors that could account for adolescent risk
      behaviours in rural communities. Qualitative research method is important in that
      they capture the complexity of life, rather than trying to 'reduce' this
      complexity, and the potential for gaining an understanding of what is going on in
      the situation with the phenomenon is greater. Focus group discussions, a
      qualitative research methodology, can yield valuable data. 

PMID- 25864977
TI  - Therapeutic work with sexually abused children.

PMID- 25864978
TI  - Counselling Survivors of Childhood Sexual Abuse (second edition).

PMID- 25864979
TI  - How to Promote Children's Social and Emotional Competence.

PMID- 25864980
TI  - Transformation through Occupation.

PMID- 25864981
TI  - Challenges for child and adolescent mental health service development in sub
      Saharan Africa.

PMID- 25864982
TI  - Diversion programmes as alternatives to the suspension and expulsion of learners.

PMID- 25864983
TI  - Integrated, highly crystalline and water stable coordination framework films on
      various substrates and water-assisted protonic conductivity.
AB  - The integrated, highly crystalline and water stable Prussian blue analogue films
      were successfully fabricated on the porous alpha-Al2O3, the conducting ITO and
      the flexible non-woven fabric substrates, respectively, using the self-assembly
      approach. The proton conduction was investigated for both powdered pellets and
      the film on the porous alpha-Al2O3 substrate. This study promotes the practical
      applications of MOF-based proton conductors in various devices. 

PMID- 25864984
TI  - The relationships between pain, disability, and health-related quality of life:
      an 8-year follow-up study of female home care personnel.
AB  - PURPOSE: To investigate the development of pain conditions, disability, and
      health-related quality of life over an 8-year period in home care personnel.
      METHOD: In earlier studies of 607 women, we reported baseline data concerning
      home care personnel. This study reports the results from an 8-year follow-up
      using a postal questionnaire. RESULTS: The questionnaire was completed by 87%.
      Prevalences of pain in upper back, lower back, and knees as well as pain
      intensity of the low back had decreased. Participants with the highest pain
      intensities of the low back at baseline had relatively lower pain intensities at
      follow-up. Anatomical spreading of pain was associated with higher average pain
      intensity. Disability had increased significantly during the time period. In the
      regression of disability at follow-up, average pain intensity together with
      disability rating index at baseline were the most important regressors; a similar
      pattern was found for quality of life. CONCLUSIONS: The development of disability
      differed from that of low-back pain intensity. Spreading of pain and pain
      intensity across the anatomical regions influenced disability and quality of life
      over 8 years. When assessing pain, it seems important to determine the spread of
      pain rather than just focusing on the area with intense pain. IMPLICATIONS FOR
      REHABILITATION: Spreading of pain and the average intensity of pain across the
      involved anatomical regions have importance for future pain and disability and
      quality of life. The clinical assessment of subjects with chronic pain prior to
      rehabilitation interventions has to determine the spreading of pain rather than
      just focusing on the area with the most intense pain. The different developments
      over time for pain intensity and disability indicate the need for applying a bio
      psycho-social view of pain both when assessing the patient with pain and when
      discussing the prognosis and course of the actual pain condition with the
      patient.

PMID- 25864985
TI  - Improved angiogenesis and healing in crush syndrome by fibroblast growth factor-2
      containing low-molecular-weight heparin (Fragmin)/protamine nanoparticles.
AB  - BACKGROUND: We produced fibroblast growth factor (FGF)-2-containing low-molecular
      weight heparin (Fragmin)/protamine nanoparticles (FGF-2 + F/P NPs). The purpose
      of this study was to evaluate the effectiveness of the local administration of
      FGF-2 + F/P NPs on repairing crush syndrome (CS)-injured lesions after
      compression release using a nonlethal and reproducible CS injury rat model.
      MATERIALS AND METHODS: The hind limbs of the anesthetized rats were compressed
      for 6 h using 3.6 kg blocks, as previously described. The effects of
      administering FGF-2 + F/P NPs (group A), F/P NPs alone (group B), FGF-2 alone
      (group C), and saline (control; group D) were examined. Motor function, surface
      blood flow in the hind limbs, and the wet/dry weight ratio in the tibialis
      anterior muscle were examined for 1-28 d after the compression release.
      Histologic analyses were also performed. RESULTS: At the middle and late stages
      (3-28 d after the compression release), group A had higher scores in the motor
      function, improved blood flow, increased number of blood vessels, and faster
      recovered muscle tissue, compared with the other groups. There was no significant
      difference in enhanced edema in the tibialis anterior muscle among all groups.
      CONCLUSIONS: The local administration of FGF-2 + F/P NPs to a CS-injured lesion
      was effective in repairing damaged muscle tissue after compression release.

PMID- 25864987
TI  - Role of neoadjuvant chemotherapy in resectable synchronous colorectal liver
      metastasis; An international multi-center data analysis using LiverMetSurvey.
AB  - BACKGROUND AND OBJECTIVES: The use of neo-adjuvant chemotherapy in resectable
      synchronous liver metastasis is ill defined. The aim of this study was to
      evaluate neo-adjuvant chemotherapy on outcomes following liver resection for
      synchronous CLM. METHODS: An analysis of a multi-centric cohort from the
      LiverMetSurvey International Registry, who had undergone curative resections for
      synchronous CLM was undertaken. Patients who received neo-adjuvant chemotherapy
      prior to liver surgery (group NAS; n = 693) were compared with those treated by
      surgery alone (group SG; n = 608). Baseline clinicopathological variables were
      compared. Predictors of overall (OS) and disease free survival (DFS) were
      subsequently identified. RESULTS: Clinicopathological comparison of the groups
      revealed a greater proportion of solitary metastasis in the SG compared to the
      NAS group (58.8% versus 38.4%; P < 0.001) therefore a separate analysis of
      solitary versus multi-centric analysis was performed. N-stage (> N1), number of
      metastasis (> 3), serum CEA (> 5 ng/ml) and no adjuvant chemotherapy
      independently predicted poorer OS, while N-stage (> N1), serum CEA (> 5 ng/ml)
      and no adjuvant chemotherapy independently predicted poorer DFS. Neo-adjuvant
      chemotherapy did not independently affect outcome. CONCLUSION: We present an
      analysis of a large multi-center series of the role of neo-adjuvant chemotherapy
      in resectable CLM and demonstrate no survival advantage in this setting.

PMID- 25864986
TI  - Cytomegalovirus prevention strategies in seropositive kidney transplant
      recipients: an insight into current clinical practice.
AB  - There is notable heterogeneity in the implementation of cytomegalovirus (CMV)
      prevention practices among CMV-seropositive (R+) kidney transplant (KT)
      recipients. In this prospective observational study, we included 387 CMV R+ KT
      recipients from 25 Spanish centers. Prevention strategies (antiviral prophylaxis
      or preemptive therapy) were applied according to institutional protocols at each
      site. The impact on the 12-month incidence of CMV disease was assessed by Cox
      regression. Asymptomatic CMV infection, acute rejection, graft function, non-CMV
      infection, graft loss, and all-cause mortality were also analyzed (secondary
      outcomes). Models were adjusted for a propensity score (PS) analysis for
      receiving antiviral prophylaxis. Overall, 190 patients (49.1%) received
      preemptive therapy, 185 (47.8%) antiviral prophylaxis, and 12 (3.1%) no specific
      intervention. Twelve-month cumulative incidences of CMV disease and asymptomatic
      infection were 3.6% and 39.3%, respectively. Patients on prophylaxis had lower
      incidence of CMV disease [PS-adjusted HR (aHR): 0.10; 95% confidence interval
      (CI): 0.01-0.79] and asymptomatic infection (aHR: 0.46; 95% CI: 0.29-0.72) than
      those managed preemptively, with no significant differences according to the
      duration of prophylaxis. All cases of CMV disease in the prophylaxis group
      occurred after prophylaxis discontinuation. There were no differences in any of
      the secondary outcomes. In conclusion, antiviral prophylaxis was associated with
      a lower occurrence of CMV disease in CMV R+ KT recipients, although such benefit
      should be balanced with the risk of late-onset disease. 

PMID- 25864988
TI  - Adiposity and Insulin Resistance in Children from a Rural Community in Mexico.
AB  - BACKGROUND AND AIMS: The study of the incidence of overweight and obesity as well
      as body composition and insulin resistance in children from rural communities is
      scarce. The aims of the study were a) to characterize the adiposity and
      homeostasis model assessment of insulin resistance (HOMA-IR) in school-age
      children from a rural community and b) to determine factors associated with fat
      mass and HOMA-IR in this population. METHODS: A total of 41 school-aged children
      (15 males and 26 females; 9.9 +/- 2.5 years old) from a Mexican rural community
      was studied. Trained observers had previously assessed the children's nutritional
      status during the first 6 months of life. Anthropometry, energy intake, physical
      activity, body composition and biochemical parameters were measured. RESULTS: The
      overall prevalence of overweight/obesity was 7.3%. The mean energy intake of
      children was below international recommendations (1,235 +/- 400 kcal/day). A
      higher percentage of fat mass was observed in females (20.3 +/- 8.5) than in
      males (14.1 +/- 5.1) (p = 0.006). There were seven children with IR, but we did
      not observe a correlation between HOMA and BMI percentiles (Pearson's r = 0.09, p
      = 0.57). In a regression model, gender (females) was the primary factor
      associated with the percentage of fat mass. The growth velocity during the first
      6 months of life was associated with HOMA-IR. CONCLUSIONS: There is a low
      frequency of overweight and obesity in children from rural communities in Mexico.
      However, these children appear to have increased risk of adiposity and insulin
      resistance.

PMID- 25864989
TI  - Associated Risk Factors for Latent Tuberculosis Infection in Subjects with
      Diabetes.
AB  - BACKGROUND AND AIMS: Type 2 diabetes mellitus (DM2) confers a higher risk for
      active tuberculosis (TB). However, information on associated risk factors for
      latent tuberculosis infection (LTBI) inpatients with DM2 is limited. We conducted
      a cross-sectional study to elucidate the prevalence of LTBI and its associated
      factors on Mexican adults with DM2 receiving medical care at the Mexican Social
      Security Institute (IMSS). METHODS: Six hundred patients with DM2 without a prior
      history of TB from outpatient diabetes clinics were enrolled in the study. The
      tuberculin-skin-test (TST) was performed. The presence of LTBI was defined by a
      TST value of >= 5 mm. A standardized interview and physical examination were
      conducted to obtain clinical, demographic, and LTBI risk factor information; all
      subjects were laboratory tested to determine the presence of exclusion criteria.
      Microscopic examination of sputum samples and chest x-rays was performed to
      identify potential active TB. Subjects with any finding suggesting active TB or
      malignancy were excluded. A logistic regression model was used to identify
      variables associated with LTBI. RESULTS: LTBI prevalence among patients with DM2
      was 51.3%. Risk factors for LTBI were living with a relative with TB, having been
      in prison, having hemoglobin values >14 g/dL, and glycosylated hemoglobin (HbA1c)
      values of > 7%. Blood pressure, economic income, or anthropometric measurements
      were not associated risk factors. CONCLUSIONS: Over one half of patients with DM
      harbor LTBI. Exposure to certain environmental conditions and poorly controlled
      DM2 (HbA1c > 7.0%) were risk factors for having LTBI in persons with DM2.

PMID- 25864991
TI  - Pharyngeal aspiration of metal oxide nanoparticles showed potential of allergy
      aggravation effect to inhaled ovalbumin.
AB  - The inhalation of manufactured metal oxide nanoparticles may lead to pulmonary
      toxicity. For instance, ZnO nanoparticles are known to induce pulmonary oxidative
      stress and inflammation. On the other hand, the pulmonary toxicity of TiO2
      nanoparticles is less than that of ZnO nanoparticles. Although, there have been
      some investigations concerning the induction of pulmonary oxidative stress and
      inflammation caused by manufactured metal oxide nanoparticles. And, although, it
      has reported that some nanoparticles cause aggravation of allergic reactions,
      there have so far been no reports regarding allergy aggravation effects of
      manufactured metal oxide nanoparticles. In this study, three types of
      nanoparticles, TiO2, ZnO and SiO2, were administered to mouse lungs by pharyngeal
      aspiration. Subsequently, the mice inhaled ovalbumin (OVA) a total of eight times
      over 3 weeks. After inhalation of OVA, the concentrations of total IgE, OVA
      specific IgE and OVA-specific IgG1 in serum increased in the mice treated with
      ZnO. TiO2 and SiO2 nanoparticles did not affect the OVA-specific IgE and IgG1
      levels. These results suggest that ZnO nanoparticles have the potential to
      aggravate allergic reactions. The results also suggest that Zn(2+) release from
      ZnO nanoparticles is involved in the aggravation potential of allergies. However,
      pharyngeal aspiration of ZnCl2 solution was not able to aggravate allergic
      reactions. Continuous Zn(2+) release from ZnO nanoparticles to the lung is
      necessary for the aggravation of allergic reactions. 

PMID- 25864990
TI  - Episodic memory and future thinking during early childhood: Linking the past and
      future.
AB  - Despite extensive examination of episodic memory and future thinking development,
      little is known about the concurrent emergence of these capacities during early
      childhood. In Experiment 1, 3-year-olds participated in an episodic memory hiding
      task ("what, when, where" [WWW] components) with an episodic future thinking
      component. In Experiment 2, a group of 4-year-olds (including children from
      Experiment 1) participated in the same task (different objects and locations),
      providing the first longitudinal investigation of episodic memory and future
      thinking. Although children exhibited age-related improvements in recall,
      recognition, and binding of the WWW episodic memory components, there were no age
      related changes in episodic future thinking. At both ages, WWW episodic memory
      performance was higher than future thinking performance, and episodic future
      thinking and WWW memory components were unrelated. These findings suggest that
      the WWW components of episodic memory are potentially less fragile than the
      future components when assessed in a cognitively demanding task.

PMID- 25864992
TI  - A prospective service evaluation of acceptance and commitment therapy for
      patients with refractory epilepsy.
AB  - OBJECTIVE: The aims of this service evaluation were to explore the effectiveness
      of a psychotherapeutic treatment for patients with epilepsy based on the
      acceptance and commitment therapy (ACT) approach and to assess whether this
      treatment is likely to be cost-effective. METHOD: We conducted an uncontrolled
      prospective study of consecutive patients with refractory epilepsy referred for
      outpatient psychological treatment to a single psychotherapist because of
      emotional difficulties related to their seizure disorder. Participants were
      referred by consultant neurologists, neuropsychologists, or epilepsy nurses,
      completed a set of validated self-report questionnaires (Short Form - 12 version
      2, Generalized Anxiety Disorder - 7, Neurological Disorders Depression Inventory
      for Epilepsy, Work and Social Adjustment Scale, and Rosenberg Self-Esteem Scale),
      and reported their seizure frequency at referral, the end of therapy, and six
      months posttherapy. Patients received a maximum of 20 sessions of one-to-one
      psychological treatment supported by a workbook. Cost-effectiveness was estimated
      based on the calculation of quality-adjusted life year (QALY) gains associated
      with the intervention. RESULTS: Sixty patients completed the prepsychotherapy and
      postpsychotherapy questionnaires, among whom 41 also provided six-month follow-up
      data. Patients received six to 20 sessions of psychotherapy (mean=11.5,
      S.D.=9.6). Psychotherapy was associated with significant medium to large positive
      effects on depression, anxiety, quality of life, self-esteem, and work and social
      adjustment (ps<.001), which were sustained six months after therapy. The mean
      cost of the psychotherapy was L445.6, and, assuming that benefits were maintained
      for at least six months after the end of therapy, the cost per QALY was estimated
      to be L11,140 (?14,119, $18,016; the cost per QALY would be half this amount if
      the benefits lasted one year). CONCLUSION: The findings of this pilot study
      indicate that the described psychotherapeutic intervention may be a cost
      effective treatment for patients with epilepsy. The results suggest that a
      randomized controlled trial of the psychotherapy program is justified.

PMID- 25864993
TI  - To do or not to do? Magnetoencephalography in the presurgical evaluation of
      epilepsy.

PMID- 25864994
TI  - Prevalence of osteopenia and osteoporosis in patients with moderate to severe
      asthma in Western Canada.
AB  - PURPOSE: Steroids, inhaled and systemic, are used to treat airway inflammation in
      patients with asthma; however, steroids are recognized to cause a number of side
      effects, including osteoporosis. We evaluated the prevalence of
      osteopenia/osteoporosis in patients with moderate-severe asthma managed through
      the Edmonton Regional Severe Asthma Centre. METHODS: We performed a retrospective
      chart review and analyzed 57 charts on patients with moderate-severe asthma
      followed through the specialty clinic, and recorded their bone mineral density
      (BMD). Steroid use was reviewed and the frequency of osteopenia/osteoporosis was
      compared in patients requiring continuous systemic steroids (Group 1, n=15),
      intermittent systemic steroids (Group 2, n=15) or inhaled steroids only (Group 3,
      n=27). RESULTS: The mean age (mean+/-SD) was 50+/-14.8 years. Cumulative systemic
      steroid dose of prednisone equivalent was higher in Group 1 (12.5 mg/day) than
      Group 2 (3.2 mg/day) (p=0.002). The frequency of osteopenia / osteoporosis was
      not significantly different between patients in Group 1(67%) and Group 2 (53%,
      p=0.46) but was significantly greater in patients from Group 1 in comparison with
      Group 3 (33%, p=0.038). CONCLUSION: Patients with moderate-severe asthma have a
      high prevalence of reduced bone density. Many patients treated with intermittent
      systemic steroids for exacerbations, or who were stable on inhaled steroids, had
      either osteopenia or osteoporosis before the age of 50. National and
      international osteoporosis guidelines should emphasize earlier screening for
      asthma patients; and increase awareness of the detrimental effects of short-term
      systemic steroids and inhaled steroids on BMD, especially when started at an
      early age and in northern climates.

PMID- 25864995
TI  - Thyroid stimulating hormone suppression post-therapy in patients with Graves'
      disease: a systematic review of pathophysiology and clinical data.
AB  - BACKGROUND: Post-treatment hypothyroidism is common in Graves' disease, and
      clinical guidelines recommend monitoring for it; however, thyroid stimulating
      hormone (TSH) can remain suppressed in these patients following treatment. The
      objectives of this study were to explore the proposed pathophysiology behind the
      phenomenon of post-therapy TSH suppression and to systematically review existing
      clinical data on post-therapy TSH suppression in patients with Graves' disease.
      SOURCE: A systematic literature search was performed using EMBASE and PubMed
      databases, with several combinations of MeSH terms. Bibliography mining was also
      done on relevant articles to be as inclusive as possible. PRINCIPAL FINDINGS: A
      total of 18 articles described possible mechanisms for post-therapy TSH
      suppression. Several of the studies demonstrate evidence of thyrotroph atrophy
      and hypothesize that this contributes to the ongoing suppression. TSH receptors
      have been identified in folliculo-stellate cells of the pituitary as well as
      astroglial cells of the hypothalamus, mediating paracrine feedback. A few studies
      have demonstrated inverse correlation between autoantibody titres and TSH levels,
      suggestive of their role in mediating ongoing TSH suppression in patients with
      Graves' disease. In addition, five studies were identified that provided clinical
      data on the duration of TSH suppression. Combined data show that 45.5% of
      patients recover TSH by 3 months after treatment, increasing to 69.3% by 6
      months, and plateauing to 73.8% by 12 months (p>0.0001). Sub-analysis also shows
      that for patients who are TBII negative, 80.7% recover their TSH by 6 months
      compared with only 58.7% in those who are TBII positive (p= 0.003). CONCLUSION:
      Clinical data suggests that TSH recovery is most likely to occur within the first
      6 months after treatment, with recovery plateauing at approximately 70% of
      patients, suggesting that reliance on this assay for monitoring can be very
      misleading. Furthermore, TBII positivity is associated with lower likelihood of
      TSH recovery. Pathophysiology behind suppressed TSH involves not only anatomical
      but also autoimmune mechanisms.

PMID- 25864996
TI  - Increased epicardial adipose tissue volume is associated with PR interval
      prolongation.
AB  - PURPOSE: Epicardial fat is visceral adipose tissue that possesses inflammatory
      properties. Inflammation and obesity are associated with cardiovascular disease
      and arrhythmogenesis, but little is known about the relationship between
      epicardial fat and PR-Interval prolongation. The purpose of this study was to
      investigate the association between epicardial adipose tissue (EAT) volume and PR
      interval prolongation as assessed by computed tomography (CT) and Twelve-lead
      ECGs. METHODS: Patients (n=287) were referred for 64-slice CT for exclusion of
      coronary artery disease and EAT volumes were determined. Twelve-lead ECGs were
      obtained from each subject and were evaluated by two independent readers.
      RESULTS: Patients with significant PR interval prolongation had higher median EAT
      volume than patients with normal PR interval. Statistically significant
      correlations were observed between the EAT volume and the PR interval (p = 0.183,
      p = 0.003), and QRS duration (p = 0.144, p = 0.018). Multivariate and trend
      analyses confirmed that EAT volume was independently associated with the presence
      of PR interval prolongation. The receiver operator characteristics curve of EAT
      volume showed that an EAT volume >144.4 cm&sup3; was associated with PR interval
      prolongation. CONCLUSION: This study indicates that EAT volume is highly
      associated with PR interval prolongation. Whether epicardial fat plays a role in
      the pathogenesis of PR interval prolongation requires future investigation.

PMID- 25864997
TI  - Serum neutrophil gelatinase-associated lipocalin levels in patients with non
      dipper hypertension.
AB  - PURPOSE: Neutrophil gelatinase-associated lipocalin (NGAL) is a protein belonging
      to the lipocalin superfamily and plays a role in atherosclerosis, renal injury
      and inflammation. The present study aimed to investigate serum NGAL
      concentrations in groups of patients with dipper and non-dipper hypertension (HT)
      and to characterize the relationship between NGAL concentration and circadian
      blood pressure in hypertensive patients. METHODS: A total of 41 (22 male, 19
      female, mean age: 56.1 +/-8.9 years) non-dipper HT patients, 40 (19 male, 21
      female, mean age: 54.0 +/-10.0 years) dipper HT patients and 42 age- and gender
      matched healthy individuals were enrolled in the study. Dipper and non-dipper HT
      were diagnosed via ambulatory blood pressure monitoring. Serum NGAL
      concentrations were measured by enzyme-linked immunosorbent assay from blood
      samples obtained from patients. RESULTS: Serum NGAL concentrations were found to
      be significantly higher in the non-dipper and dipper HT patient groups in
      comparison with the control group (84.9 +/-23.0 ng/ml and 62.1 +/-17.8 vs. 46.6
      +/- 13.7 ng/ml, p <0.017, respectively). Moreover, serum NGAL concentrations were
      significantly higher in the non-dipper HT group in comparison with the dipper HT
      group (p<0.017). Serum NGAL concentration showed significant correlation with
      overall ambulatory BP levels both in non-dipper and dipper HP groups. CONCLUSION:
      Serum NGAL concentrations increased significantly in non-dipper HT patients in
      comparison with dipper HT patients and normotensive patients and show significant
      correlation with ambulatory BP levels. Serum NGAL concentration might be a useful
      marker in identifying HT patients with higher risk for cardiovascular mortality.

PMID- 25864998
TI  - Quality of Life Following Treatment of Trochanteric Fractures with Proximal
      Femoral Nail versus Cementless Bipolar Hemiarthroplasty in Elderly.
AB  - PURPOSE: There is currently no gold standard treatment for unstable
      intertrochanteric fractures of the elderly. Internal fixation and
      hemiarthroplasty are two common treatment methods but studies comparing the
      functional outcomes of these procedures in the elderly are limited. This study
      evaluates the functional outcomes of hip fracture patients treated either with
      internal fixation or hemiarthroplasty. METHODS: Eighty-six elderly (>60 years)
      patients who presented with isolated, unstable intertrochanteric fractures
      between 2009 and 2013 were included in the study. According to the classification
      of Association for Osteosynthesis/Orthopaedic Trauma Association; 12 of the
      patients had a 31A1.3 fracture type, 36 of the patients had 31A2.2 and 19 had
      31A2.3 fracture type, 12 had 31A3.1 and seven had 31A3.3 fracture. Forty-two of
      86 hip patients (Group 1) were treated with intramedullary nailing and
      antirotator proximal femoral nail implant (TST, Turkey), and 44 (Group 2) were
      treated with cementless bipolar hemiarthroplasty. Preoperative social function
      (Jensen) score, EQ-5D index score and mobility (Palmer/Parker) scores were
      obtained. Five dimensions of EQ-5D were obtained at every follow-up visit until
      24 months postoperative. RESULTS: There was no statistically significant
      difference between two groups according to preoperative demographic variables,
      including mean age and sex and Jensen, Palmer/Parker,EQ-5D index, five dimensions
      of EQ-5D and American Society of Anesthesiologists scores. At end of 24 months
      follow-up, health-related quality of life had increased more in Group 1 and they
      reported better social functioning and mobility scores (p<0.01). CONCLUSION:
      Internal fixation resulted in better social functioning and mobility scores
      compared with cementless bipolar hemiarthroplasty at the end of 24 months in
      treatment of unstable pertrochanteric hip fracture in the elderly.

PMID- 25864999
TI  - HSA-based phosphorescent probe for two-photon in vitro visualization.
AB  - Two-photon microscopy reveals several advantages over conventional one since it
      provides higher spatial resolution as well as deeper penetration into the sample
      under study. The development of suitable two-photon probes is one of the most
      challenging tasks in this area. Here we present phosphorescent non-covalent
      adduct of human serum albumin and Au-Ag alkynyl-diphosphine complex,
      [Au14Ag4(C2Ph)12(PPh2C6H4PPh2)6][PF6]4, which exhibits high cross section of two
      photon-induced luminescence (deltaTPE) within large near-infrared excitation
      wavelength region (700-800 nm) with maximum deltaTPE about 38 GM at 740 nm. This
      feature makes it a promising probe for multiphoton bioimaging as demonstrated by
      successful visualization of glioma C6 cells and various tissues by two-photon
      confocal microscopy both in planar and z-stacking modes. Additionally, the broad
      excitation region enables optimization of the signal-to-background auto
      fluorescence ratio via variation of excitation wavelength.

PMID- 25865000
TI  - Reactions of model proteins with aurothiomalate, a clinically established gold(I)
      drug: The comparison with auranofin.
AB  - Aurothiomalate (AuTm) is an old, clinically established, antiarthritic gold drug
      that is currently being reconsidered as a candidate drug for cancer treatment and
      for other therapeutic indications within a more general drug repositioning
      program. As the biological effects of gold drugs seem to be mediated, mainly, by
      their interactions with protein targets we have analyzed here, in detail, the
      metalation patterns produced by aurothiomalate in a few model proteins. In
      particular, the reactions of aurothiomalate with the small proteins ribonuclease
      A, cytochrome c and lysozyme were explored through ESI MS (electrospray
      ionization mass spectrometry) analysis. Notably, characteristic and rather
      constant features emerged in the protein metalation patterns induced by AuTm that
      are markedly distinct from those caused by auranofin; a non-covalent interaction
      mode is invoked for AuTm binding to the mentioned proteins. The affinity
      constants of AuTm toward the three mentioned proteins were also initially
      assessed. The implications of the present findings are discussed. 

PMID- 25865003
TI  - Adaptive immunity & vaccination.

PMID- 25865002
TI  - Clinical and immunological characteristics in 552 systemic lupus erythematosus
      patients in a southern province of China.
AB  - AIM: The purpose of this study was to gain a better understanding of systemic
      lupus erythematosus (SLE) in Hakka populations. METHODS: We studied the
      demographic, clinical and laboratory characteristics in a cohort of 552 SLE
      patients diagnosed at the Rheumatology Department in MeiZhou People's Hospital
      from January 2008 to December 2012. There were 495 women and 57 men (8.7 : 1)
      with a mean age of 35.3 years (range 12-78 years). The mean age at disease onset
      and the mean disease duration were 31.8 +/- 14.4 years and 3.3 +/- 2.8 years,
      respectively. RESULTS: The most common clinical manifestations were arthritis
      (61.6%), followed by malar rash (52.7%), photosensitivity (22.8%), mouth ulcers
      (17.0%) and discoid lupus (14.7%). The prevalence was 46.7% for nephritis (by
      biopsy), 18.3% for pleuritis, 15.6% for pericarditis and 4.9% for
      neuropsychiatric manifestations. The most common hematological manifestations
      were anemia (63.8%), followed by leucopenia (29.0%) and thrombocytopenia (14.9%).
      Antinuclear antibodies were detected in 99.8% of patients, followed by anti
      double-stranded DNA (81.3%), anti-SSA (Sjogren's syndrome antigen A)/Ro (58.7%),
      anti-ribonucleoprotein (36.8%), anti-Sm (35.7%), and anti-SSB/La (15.0%). Anti
      cardiolipin immunoglobulin G (IgG) and IgM were detected in 18.3% and 14.1% of
      patients, respectively. Active disease and infections were the two major causes
      of death. CONCLUSION: The clinical and immunological characteristics of the SLE
      patients in our study place our population in the middle of the spectrum between
      other Asian and Caucasian populations.

PMID- 25865001
TI  - Caged oligonucleotides for studying biological systems.
AB  - Light-activated ("caged") compounds have been widely employed for studying
      biological processes with high spatial and temporal control. In the past decade,
      several new approaches for caging the structure and function of DNA and RNA
      oligonucleotides have been developed. This review focuses on caged
      oligonucleotides that incorporate site-specifically one or two photocleavable
      linkers, whose photolysis yields oligonucleotides with dramatic structural and
      functional changes. This technique has been employed by our laboratory and others
      to photoregulate gene expression in cells and living organisms, typically using
      near UV-activated organic chromophores. To improve capabilities for in vivo
      studies, we harnessed the rich inorganic photochemistry of ruthenium bipyridyl
      complexes to synthesize Ru-caged morpholino antisense oligonucleotides that
      remain inactive in zebrafish embryos until uncaged with visible light. Expanding
      into new caged oligonucleotide applications, our lab has developed Transcriptome
      In Vivo Analysis (TIVA) technology, which provides the first noninvasive,
      unbiased method for isolating mRNA from single neurons in brain tissues. TIVA
      isolated mRNA can be amplified and then analyzed using next-generation sequencing
      (RNA-seq). 

PMID- 25865004
TI  - Pigmentation & melanoma.

PMID- 25865006
TI  - Tissue regeneration & wound healing.

PMID- 25865005
TI  - Skin & hair developmental biology.

PMID- 25865009
TI  - Carcinogenesis & cancer genetics.

PMID- 25865010
TI  - Clinical research (observations, pathophysiology & outcomes).

PMID- 25865011
TI  - Epidemiology.

PMID- 25865012
TI  - Epidermal structure & barrier function.

PMID- 25865013
TI  - Gene therapy & clinical therapeutics.

PMID- 25865014
TI  - Genetic disease & gene regulation.

PMID- 25865015
TI  - Growth factors.

PMID- 25865016
TI  - Innate immunity, inflammation & microbiology.

PMID- 25865018
TI  - Photobiology.

PMID- 25865017
TI  - Auto-immunity.

PMID- 25865019
TI  - Pyrolysis of drugs of abuse: a comprehensive review.
AB  - This review summarizes the literature to date relating to pyrolysis and heated
      vapour ingestion of drugs of abuse. In this context, heating is referred to as
      smoking or pyrolysis, but these are generic descriptors that encompass numerous
      methods of vapour generation and inhalation. Depending on the amount of drug
      used, diluents and contaminants present, heating conditions, and the
      oxidative/reductive environment, many thermal decomposition products can be
      formed. In addition to the recognized hazard of rapid onset of pharmacological
      effects of the parent drug, thermal decomposition products may be
      pharmacologically active as well as acutely/chronically toxic. For example,
      several published reports have linked heroin smoking to a form of brain
      encephalopathy and to the development of movement disorders. Early qualitative
      studies focusing on the thermal decomposition of drugs have evolved into more
      complex investigations employing mass spectral identification, confirmation, and
      elucidation of formation mechanism. In most cases, thermal decomposition begins
      with cleavage of the weakest bond (often C-N) to generate free radicals that then
      form the most stable sterically favoured products. Several reports of
      rearrangements at higher temperatures have been identified and hint at an
      underlying complexity that arises from the variety of smoking methods and
      conditions. Given that many designer drugs such as synthetic cannabinoids are
      ingested primarily through smoking, this issue has taken on new importance.

PMID- 25865020
TI  - Use of hormonal therapy is associated with reduced nerve fiber density in deep
      infiltrating, rectovaginal endometriosis.
AB  - OBJECTIVE: To study the density of nerve fibers in cases of deep infiltrating
      endometriosis (DIE) of the rectovaginal septum in relation to various clinical
      factors. DESIGN: A research laboratory-based study. SETTING: A tertiary center
      together with a research laboratory. METHODS: Archived DIE tissue samples from 45
      women operated upon for rectovaginal septum DIE were re-examined histologically,
      and by immunohistochemistry. MAIN OUTCOME MEASURES: The effect of progestogens or
      combined oral contraceptives on the density of nerve fibers, and the expression
      of nerve growth factor (NGF) and its high-affinity receptor (tyrosine kinase
      receptor A, Trk-A). RESULTS: The use of hormonal therapy was associated with
      reduced densities of sympathetic, parasympathetic and sensory nerve fibers in DIE
      lesions. Density of total nerve fibers (with pan-neuronal marker PGP9.5) was
      significantly lower (p < 0.05) in lesions collected from hormone-treated women
      (8.6/mm2, 4.2-20.8/mm2; median density, from 25th to 75th quartiles) compared
      with that in lesions from untreated women (24.9/mm2, 11.2-34.9/mm2). DIE lesions
      stained strongly for NGF and its receptor Trk-A. Expression of NGF, but not of
      Trk-A, was significantly reduced during use of hormonal therapy. CONCLUSIONS: Use
      of hormonal therapy was associated with significantly reduced nerve fiber density
      in DIE lesions. This may be an important mechanism of action of hormonal therapy
      for controlling DIE pain symptoms. The expression of estrogen-regulated NGF and
      its receptor was only partially suppressed during the use of hormonal therapy,
      suggesting that local estrogen action is often maintained during conventional
      hormonal therapy in cases of DIE.

PMID- 25865021
TI  - Did we IMPROVE-IT: thoughts on LDL targeting post-trial?
AB  - Interview with Professor Chris Packard, MD, PhD by Tanya Stezhka (Commissioning
      Editor) The IMPROVE-IT trial, launched 9 years ago, has finally provided
      physicians with long-term efficacy and safety evidence for ezetimibe. The large
      scale study in acute-coronary-syndrome patients showed a clear benefit in
      reducing cardiovascular events when added to simvastatin in this population. The
      size of the benefit was proportionate to the reduction in LDL cholesterol. We
      spoke to Professor Chris Packard (University of Glasgow, UK) about his interest
      in the trial, and the importance of lowering LDL and research in the wider
      clinical context. 

PMID- 25865022
TI  - Incremental Value of Pocket-Sized Echocardiography in Addition to Physical
      Examination during Inpatient Cardiology Evaluation: A Multicenter Italian Study
      (SIEC).
AB  - BACKGROUND: We prospectively assessed the incremental value of a pocket-sized
      echocardiography (PSE) device during cardiology consultations, in addition to
      physical examination, ECG reading, and chest x-ray. METHODS: A total of 443
      consecutive patients (53% men), referred for bedside consultations, underwent
      physical examination, ECG, and CXR, followed by PSE examination. The physician
      completed a detailed questionnaire (clinical and echocardiographic data, scanning
      time, abnormal results). Receiver operating characteristic (ROC) curve analysis
      was generated to test the predictive discrimination value of the different
      methods. The incremental value of PSE examination compared to clinical visit
      alone or combined with ECG results was expressed as a global chi-square value.
      RESULTS: The PSE examination did not influence the definitive diagnosis in only
      23.5% of cases, while 25.3% of the diagnoses were confirmed and verified by PSE.
      The clinical diagnosis was enriched by PSE in 21.9% of cases, and the diagnosis
      was changed in 26.2%. The area under curve (AUC) of physical examination + ECG
      results (sensitivity: 80%; specificity: 67%) was significantly higher than
      physical examination alone (sensitivity: 75%; specificity: 62%) (P < 0.0002), and
      the AUC of PSE results (sensitivity: 88%; specificity: 86%) was significantly
      higher than physical examination + ECG results (P < 0.0001). The PSE results,
      combined with clinical and ECG results, had a significant incremental diagnostic
      value during cardiology consultation when compared to the clinical visit alone or
      with ECG results (P < 0.0001). CONCLUSIONS: PSE had an incremental diagnostic
      value during bedside cardiology consultation, increasing the number of
      appropriate diagnoses and reducing the routine use of echocardiography.

PMID- 25865023
TI  - Histological and hormonal changes in the European eel (Anguilla anguilla) after
      exposure to environmental cocaine concentration.
AB  - The aim of this study was the assessment of histological and hormonal changes
      induced in the European eel from environmental concentrations of cocaine. Silver
      eels were exposed to 20 ng L(-1) of cocaine during 50 days; at the same time,
      control, vehicle control and two post-exposure recovery groups (3 and 10 days)
      were made. The general morphology of the skin and the intestine, and the plasma
      levels of prolactin, cortisol and dopamine were evaluated. In the skin, cocaine
      decreased the number and size of mucous cells, increased the thickness of the
      epidermis and altered the club cells and the basal lamina. In the intestine,
      cocaine increased the thickness of the epithelium and the number of mucous cells
      and reactivated the structure of the intestine and of the intestinal musculature.
      Moreover, cocaine increased plasma prolactin, cortisol and dopamine levels. These
      results suggest that cocaine induced histological changes, directly and/or
      through the hormonal changes observed. Considering the complex life cycle of the
      eel, the changes induced by cocaine in the skin, the intestine and the endocrine
      system could threaten the ability of the eel to successfully migrate and
      reproduce. 

PMID- 25865024
TI  - Evaluating sexual dimorphism in the human mastoid process: A viewpoint on the
      methodology.
AB  - The mastoid process is one of the most sexually dimorphic features in the human
      skull, and is therefore often used to identify the sex of skeletons. Numerous
      techniques for assessing variation in the size and shape of the mastoid process
      have been proposed and implemented in osteological research, but its complex form
      still presents difficulties for consistent and effective analysis. In this
      article, we compare the different techniques and variables that have been used to
      define, measure, and visually score sexual dimorphism in the mastoid process. We
      argue that the current protocols fail to capture the full morphological range of
      this bony projection, and suggest ways of improving and standardizing them,
      regarding both traditional and 3D-based approaches.

PMID- 25865025
TI  - Ultrasound-enhanced bevacizumab release from echogenic liposomes for inhibition
      of atheroma progression.
AB  - CONTEXT: Bevacizumab (BEV) is a monoclonal antibody to vascular endothelial
      growth factor (VEGF) that ameliorates atheroma progression by inhibiting
      neovascularization. OBJECTIVE: We aimed to determine whether BEV release from
      echogenic liposomes (BEV-ELIP) could be enhanced by color Doppler ultrasound (US)
      and whether the released BEV inhibits VEGF expression by endothelial cells in
      vitro. MATERIALS AND METHODS: BEV-ELIP samples were subjected to 6 MHz color
      Doppler ultrasound (MI = 0.4) for 5 min. We assessed release of BEV with a direct
      ELISA and with fluoresceinated BEV (FITC-BEV) loaded into ELIP by the same
      method. Human umbilical vein endothelial cell (HUVEC) cultures were stimulated to
      express VEGF by 10 nM phorbol-12-myristate 13-acetate (PMA). Cell-associated VEGF
      levels were determined using a cell-based ELISA. RESULTS: Overall, US caused an
      additional 100 ug of BEV to be released or exposed per BEV-ELIP aliquot within 60
      min BEV-ELIP treated with US inhibited VEGF expression by 90% relative to non
      treated controls and by 70% relative to BEV-ELIP without US. Also, US-treated BEV
      ELIP inhibited HUVEC proliferation by 64% relative to untreated controls and by
      45% relative to BEV-ELIP without US. DISCUSSION AND CONCLUSION: We have
      demonstrated that BEV-ELIP retains its VEGF-binding activity in a liposomal
      formulation and that clinical Doppler US can significantly increase that
      activity, both by releasing free BEV and by enhancing the surface exposure of the
      immunoreactive antibody.

PMID- 25865026
TI  - Central nervous system lymphoma presenting as trigeminal neuralgia: A diagnostic
      challenge.
AB  - We describe an atypical man with diffuse large B cell lymphoma localized to the
      sphenoid wing and adjacent cavernous sinus, initially presenting with isolated
      ipsilateral facial pain mimicking trigeminal neuralgia due to invasion of
      Meckel's cave but subsequently progressing to intra-axial extension and having
      synchronous features of systemic lymphoma. Primary central nervous system
      lymphoma is uncommon, accounting for approximately 2% of all primary intracranial
      tumors, but its incidence has been steadily increasing in some groups [1]. It
      usually arises in the periventricular cerebral white matter, and reports of
      lymphoma in extra-axial regions are rare [2]. This man highlights the importance
      of maintaining lymphoma in the differential diagnosis of tumors of the skull base
      presenting with trigeminal neuralgia-like symptoms. 

PMID- 25865027
TI  - Hyperdense suprasellar mass: An unusual radiological presentation of intracranial
      dermoid cyst.
AB  - We report an exceedingly rare patient with a hyperdense suprasellar dermoid cyst
      and a pertinent review of the literature. Intracranial dermoid tumors are rare
      congenital lesions of the brain that account for less than 1% of all intracranial
      tumors. Even though they are rare, typical CT scan and MRI features and location
      allow radiological diagnosis in the majority of patients. Radiologically, dermoid
      cysts typically present as low density masses on CT scan and are generally
      hyperintense on T1-weighted MRI sequences with variable signal on T2-weighted
      sequences. The recognition of atypical features can avoid diagnostic pitfalls and
      is clinically relevant for overall surgical management. 

PMID- 25865028
TI  - Redox-Mediated Synthesis of a Fe3O4-MnO2 Nanocomposite for Dye Adsorption and
      Pseudocapacitance.
AB  - A logically chosen redox reaction of submerged Fe(0) in an aqueous KMnO4 solution
      has been reported. The template-free reaction conditions produced gram amounts of
      a hierarchical flowerlike Fe3O4-MnO2 nanocomposite. More precisely, freshly
      prepared Fe(0) nanoparticles were prepared from air-free hot water under
      submerged conditions using a door magnet. The black Fe(0) particles were oxidized
      in water quantitatively by KMnO4 in the solution phase and the nanocomposite was
      prepared. The material has been used as a dye adsorbent and the representative
      cationic dye uptake, recovery, and recycling of the dye becomes easy owing to the
      ferromagnetic properties and surface negative charge of the material. The
      nanocomposite also showed a higher specific capacitance (327 F g(-1) at 10 mV s(
      1)) than the reported values of pure MnO2 and Fe3O4. The material exhibited a
      high energy density as well as a high power density, and remained stable even
      after a large number of charge-discharge cycles.

PMID- 25865030
TI  - Cholinergic, but not NMDA, receptors in the lateral entorhinal cortex mediate
      acquisition in trace eyeblink conditioning.
AB  - Anatomical and electrophysiological studies collectively suggest that the
      entorhinal cortex consists of several subregions, each of which is involved in
      the processing of different types of information. Consistent with this idea, we
      previously reported that the dorsolateral portion of the entorhinal cortex (DLE),
      but not the caudomedial portion, is necessary for the expression of a memory
      association between temporally discontiguous stimuli in trace eyeblink
      conditioning (Morrissey et al. (2012) J Neurosci 32:5356-5361). The present study
      examined whether memory acquisition depends on the DLE and what types of local
      neurotransmitter mechanisms are involved in memory acquisition and expression.
      Male Long-Evans rats experienced trace eyeblink conditioning, in which an
      auditory conditioned stimulus (CS) was paired with a mildly aversive electric
      shock to the eyelid (US) with a stimulus-free interval of 500 ms. Immediately
      before the conditioning, the rats received a microinfusion of neuroreactive
      substances into the DLE. We found that reversible inactivation of the DLE with
      GABAA receptor agonist, muscimol impaired memory acquisition. Furthermore,
      blockade of local muscarinic acetylcholine receptors (mACh) with scopolamine
      retarded memory acquisition while blockade of local NMDA receptors with APV had
      no effect. Memory expression was not impaired by either type of receptor blocker.
      These results suggest that the DLE is necessary for memory acquisition, and that
      acquisition depends on the integrity of local mACh receptor-dependent firing
      modulation, but not NMDA receptor-dependent synaptic plasticity.

PMID- 25865031
TI  - Knowledge mobilization to spread awareness of the 'F-words' in childhood
      disability: lessons from a family-researcher partnership.
AB  - BACKGROUND: In 2012, two CanChild researchers published an article in Child:
      Care, Health and Development titled 'The "F-words" in childhood disability: I
      swear this is how we should think!' Building on the World Health Organization's
      International Classification of Functioning, Disability and Health (ICF)
      framework, the article featured key strengths-based ICF themes (i.e. the 'F
      words' - Function, Family, Fitness, Fun, Friends and Future). This paper reports
      on a knowledge mobilization initiative designed to spread awareness of the 'F
      words' ideas. METHODS: Families and researchers collaborated to develop,
      disseminate and evaluate an online awareness video. The video used written
      descriptions, parents' reflections and their pictures, music and graphics to
      captivate the audience. Posted on the CanChild website in May 2014, information
      about the video was distributed via various dissemination strategies and
      evaluated by tracking its views and through an online survey. RESULTS: After a 2
      month evaluation, there were 715 views and 137 survey responses. Of the survey
      responses, 89% lived in Canada, 55% had not previously heard of the 'F-words',
      98% 'extremely liked'/'liked the ideas' and 88% indicated they would share the
      video. CONCLUSIONS: By creating a short and captivating video, we were able to
      spread awareness to a wide audience in a short period of time. Engaging families
      throughout the project was critical to the success of the video. By working
      together, we hope to continue bridging research and practice and moving the 'F
      words' concepts forward one 'word' at a time.

PMID- 25865029
TI  - Simultaneous evaluation of vascular morphology, blood volume and transvascular
      permeability using SPION-based, dual-contrast MRI: imaging optimization and
      feasibility test.
AB  - Exploiting ultrashort-T(E) (UTE) MRI, T1-weighted positive contrast can be
      obtained from superparamagnetic iron oxide nanoparticles (SPIONs), which are
      widely used as a robust T2-weighted, negative contrast agent on conventional MR
      images. Our study was designed (a) to optimize the dual-contrast MRI method using
      SPIONs and (b) to validate the feasibility of simultaneously evaluating the
      vascular morphology, blood volume and transvascular permeability using the dual
      contrast effect of SPIONs. All studies were conducted using 3 T MRI. According to
      numerical simulation, 0.15 mM was the optimal blood SPION concentration for
      visualizing the positive contrast effect using UTE MRI (T(E) = 0.09 ms), and a
      flip angle of 40 degrees  could provide sufficient SPION-induced enhancement and
      acceptable measurement noise for UTE MR angiography. A pharmacokinetic study
      showed that this concentration can be steadily maintained from 30 to 360 min
      after the injection of 29 mg/kg of SPIONs. An in vivo study using these settings
      displayed image quality and CNR of SPION-enhanced UTE MR angiography (image
      quality score 3.5; CNR 146) comparable to those of the conventional, Gd-enhanced
      method (image quality score 3.8; CNR 148) (p > 0.05). Using dual-contrast MR
      images obtained from SPION-enhanced UTE and conventional spin- and gradient-echo
      methods, the transvascular permeability (water exchange index 1.76-1.77),
      cerebral blood volume (2.58-2.60%) and vessel caliber index (3.06-3.10) could be
      consistently quantified (coefficient of variation less than 9.6%; Bland-Altman
      95% limits of agreement 0.886-1.111) and were similar to the literature values.
      Therefore, using the optimized setting of combined SPION-based MRI techniques,
      the vascular morphology, blood volume and transvascular permeability can be
      comprehensively evaluated during a single session of MR examination.

PMID- 25865032
TI  - A childhood subepidermal autoimmune bullous disease resembling mechanobullous
      epidermolysis bullosa acquisita.

PMID- 25865033
TI  - Molecular detection of Rickettsia bellii in Amblyomma rotundatum from imported
      red-footed tortoise (Chelonoides carbonaria).
AB  - Introduction of exotic ticks and pathogens through international animal trade
      (farm animals and pets) is a serious threat to public health and local fauna.
      Rapid and correct identification of potential threats is an important step on the
      way to conduct an efficient control of imported pests. In this report we describe
      the molecular identification of the neotropic tick Amblyomma rotundatum
      intercepted from red-footed tortoise (Chelonoides carbonaria), imported to Israel
      from Florida, USA. Molecular analysis of the ticks conducted upon their
      identification, revealed that they were infected with Rickettsia bellii.
      Following their collection, the ticks were examined morphologically and five
      molecular markers were used to determine their taxonomic identity: cytochrome c
      oxidase subunit 1 (COX1), cytochrome b (CytB), 12S rRNA, 16S rRNA and internal
      transcribed sequence 2 (ITS-2). Molecular analysis indicated that all of the
      collected ticks were Amblyomma rotundatum. Using rickettsial gltA (citrate
      synthase) gene in real-time PCR analysis we found that approximately 25% of the
      intercepted ticks (8 of 33) were infected with Rickettsia bellii. It is concluded
      that accurate and timely identification of imported exotic ticks prevented their
      introduction to Israel, and that use of molecular tools may further improve the
      response to such potential threats. 

PMID- 25865035
TI  - The evolution of peer review as a basis for scientific publication: directional
      selection towards a robust discipline?
AB  - Peer review is pivotal to science and academia, as it represents a widely
      accepted strategy for ensuring quality control in scientific research. Yet, the
      peer-review system is poorly adapted to recent changes in the discipline and
      current societal needs. We provide historical context for the cultural lag that
      governs peer review that has eventually led to the system's current structural
      weaknesses (voluntary review, unstandardized review criteria, decentralized
      process). We argue that some current attempts to upgrade or otherwise modify the
      peer-review system are merely sticking-plaster solutions to these fundamental
      flaws, and therefore are unlikely to resolve them in the long term. We claim that
      for peer review to be relevant, effective, and contemporary with today's
      publishing demands across scientific disciplines, its main components need to be
      redesigned. We propose directional changes that are likely to improve the
      quality, rigour, and timeliness of peer review, and thereby ensure that this
      critical process serves the community it was created for. 

PMID- 25865034
TI  - Infant temperament: stability by age, gender, birth order, term status, and
      socioeconomic status.
AB  - Two complementary studies focused on stability of infant temperament across the
      1st year and considered infant age, gender, birth order, term status, and
      socioeconomic status (SES) as moderators. Study 1 consisted of 73 mothers of
      firstborn term girls and boys queried at 2, 5, and 13 months of age. Study 2
      consisted of 335 mothers of infants of different gender, birth order, term
      status, and SES queried at 6 and 12 months. Consistent positive and negative
      affectivity factors emerged at all time points across both studies. Infant
      temperament proved stable and robust across gender, birth order, term status, and
      SES. Stability coefficients for temperament factors and scales were medium to
      large for shorter (< 9 months) interassessment intervals and small to medium for
      longer (> 10 months) intervals. 

PMID- 25865037
TI  - Prenatal ethanol increases ethanol intake throughout adolescence, alters ethanol
      mediated aversive learning, and affects MU but not delta or kappa opioid receptor
      mRNA expression.
AB  - Animal models of prenatal ethanol exposure (PEE) have indicated a facilitatory
      effect of PEE on adolescent ethanol intake, but few studies have assessed the
      effects of moderate PEE throughout adolescence. The mechanisms underlying this
      facilitatory effect remain largely unknown. In the present study, we analysed
      ethanol intake in male and female Wistar rats with or without PEE (2.0 g/kg,
      gestational days 17-20) from postnatal days 37 to 62. The results revealed
      greater ethanol consumption in PEE rats than in controls, which persisted
      throughout adolescence. By the end of testing, ethanol ingestion in PEE rats was
      nearly 6.0 g/kg. PEE was associated with insensitivity to ethanol-induced
      aversion. PEE and control rats were further analysed for levels of MU, delta and
      kappa opioid receptor mRNA in the infralimbic cortex, nucleus accumbens shell,
      and ventral tegmental area. Similar levels of mRNA were observed across most
      areas and opioid receptors, but MU receptor mRNA in the ventral tegmental area
      was significantly increased by PEE. Unlike previous studies that assessed the
      effects of PEE on ethanol intake close to birth, or in only a few sessions during
      adolescence, the present study observed a facilitatory effect of PEE that lasted
      throughout adolescence. PEE was associated with insensitivity to the aversive
      effect of ethanol, and increased levels of MU opioid receptor transcripts. PEE is
      a prominent vulnerability factor that probably favors the engagement of
      adolescents in risky trajectories of ethanol use.

PMID- 25865036
TI  - Measuring Binding Kinetics of Antibody-Conjugated Gold Nanoparticles with Intact
      Cells.
AB  - Antibody-conjugated nanomaterials have attracted much attention because of their
      applications in nanomedicine and nanotheranostics, and amplification of detection
      signals. For many of these applications, the nanoconjugates must bind with a cell
      membrane receptor (antigen) specifically before entering the cells and reaching
      the final target, which is thus important but not well understood. Here, a
      plasmonic imaging study of the binding kinetics of antibody-conjugated gold
      nanoparticles with antigen-expressing cells is presented, and the results are
      compared with that of the nanoparticle-free antibody. It is found that the
      nanoconjugates can significantly affect the binding kinetics compared with free
      antibody molecules, depending on the density of the antibody conjugated on the
      nanoparticles, and expressing level of the antigen on the cell membrane. The
      results are analyzed in terms of a transition from monovalent binding model to a
      bivalent binding model when the conjugation density and expressing level
      increase. These findings help optimize the design of functional nanomaterials for
      drug delivery and correct interpretation of data obtained with nanoparticle
      signal amplification. 

PMID- 25865038
TI  - Pharmacognostic standardization and preliminary phytochemical studies of
      Gaultheria trichophylla.
AB  - CONTEXT: Gaultheria trichophylla Royle (Ericaceae) has long been used for various
      ailments in traditional systems of medicines; most importantly it is used against
      pain and inflammation. AIMS: This study determines various pharmacognostic and
      phytochemical standards helpful to ensure the purity, safety, and efficacy of
      medicinal plant G. trichophylla. MATERIAL AND METHODS: Intact aerial parts,
      powdered materials, and extracts were examined macro- and microscopically and
      pharmacognostic standardization parameters were determined in accordance with the
      guidelines given by the World Health Organization (WHO). Parameters including
      extractive values, ash values, and loss on drying were determined. Preliminary
      phytochemical tests, fluorescence analysis, and chromatographic profiling were
      performed for the identification and standardization of G. trichophylla. RESULTS:
      The shape, size, color, odor, and surface characteristics were noted for intact
      drug and powdered drug material of G. trichophylla. Light and scanning electron
      microscope images of cross section of leaf and powdered microscopy revealed
      useful diagnostic features. Histochemical, phytochemical, physicochemical, and
      fluorescence analysis proved useful tools to differentiate the powdered drug
      material. High-performance liquid chromatography (HPLC) analysis showed the
      presence of important phytoconstituents such as gallic acid, rutin, and
      quercetin. DISCUSSION AND CONCLUSIONS: The data generated from the present study
      help to authenticate the medicinally important plant G. trichophylla. Qualitative
      and quantitative microscopic features may be helpful for establishing the
      pharmacopeia standards. Morphology as well as various pharmacognostic aspects of
      different parts of the plant were studied and described along with phytochemical
      and physicochemical parameters, which could be helpful in further isolation and
      purification of medicinally important compounds.

PMID- 25865039
TI  - Repair of osteochondral defects in a rabbit model using a porous hydroxyapatite
      collagen composite impregnated with bone morphogenetic protein-2.
AB  - Articular cartilage has a limited capacity for spontaneous repair, and an
      effective method to repair damaged articular cartilage has not yet been
      established. The purpose of this study was to evaluate the effect of
      transplantation of porous hydroxyapatite collagen (HAp/Col) impregnated with bone
      morphogenetic protein-2 (BMP-2). To evaluate the characteristics of porous
      HAp/Col as a drug delivery carrier of recombinant human BMP-2 (rhBMP-2), the
      rhBMP-2 adsorption capacity and release kinetics of porous HAp/Col were analyzed.
      Porous HAp/Col impregnated with different amounts of rhBMP-2 (0, 5, and 25 MUg)
      was implanted into osteochondral defects generated in the patellar groove of
      Japanese white rabbits to evaluate the effect on osteochondral defect
      regeneration. At 3, 6, 12, and 24 weeks after operation, samples were harvested
      and subjected to micro-computed tomography analysis and histological evaluation
      of articular cartilage and subchondral bone repair. The adsorption capacity was
      329.4 MUg of rhBMP-2 per cm(3) of porous HAp/Col. Although 36% of rhBMP-2 was
      released within 24 h, more than 50% of the rhBMP-2 was retained in the porous
      HAp/Col through the course of the experiment. Defects treated with 5 MUg of rhBMP
      2 showed the most extensive subchondral bone repair and the highest histological
      regeneration score, and differences against the untreated defect group were
      significant. The histological regeneration score of defects treated with 25 MUg
      of rhBMP-2 increased up to 6 weeks after implantation, but then decreased. Porous
      HAp/Col, therefore, is an appropriate carrier for rhBMP-2. Implantation of porous
      HAp/Col impregnated with rhBMP-2 is effective for rigid subchondral bone repair,
      which is important for the repair of the smooth articular surface.

PMID- 25865040
TI  - Selenate as a novel ligand for keplerate chemistry. New {W72Mo60} keplerates with
      selenates inside the cavity.
AB  - The synthesis and characterization of three novel keplerate-type compounds
      containing the {W72Mo60} mixed-metal core are reported. Complexes
      (NH4)72[{W6O21(H2O)6}12{Mo2O4(SeO4)}30].150H2O.6(NH4)2SeO4 (1a) and
      (NH4)25(NH2Me2)47[{W6O21(H2O)6}12{Mo2O4(SeO4)}30].130H2O.3(NH4)2SeO4 (1b) were
      prepared by ligand substitution from the acetate anionic complex
      [{W6O21(H2O)5(CH3COO)0.5}12{Mo2O4(CH3COO)}30](48-) and selenate. The selenate
      anions in keplerate ions [{W6O21(H2O)6}12{Mo2O4(SeO4)}30](72-) are very labile
      and easily aquate with the formation of
      [{W6O21(H2O)6}12{Mo2O4}30(SeO4)20(H2O)20](52-), which was isolated as
      (NH4)20(NH2Me2)32[{W6O21(H2O)6}12{Mo2O4}30(SeO4)20(H2O)20].150H2O (2) and
      structurally characterized. In the crystal structure of 2 selenate has several
      coordination modes, preferentially bonding to the {Mo2O4}(2+) units, and,
      additionally, to the {(W)W5} pentagonal blocks. The compounds have been
      characterized by elemental analysis, Raman, IR and (77)Se NMR spectroscopy, and
      by ESI mass spectrometry. Capillary electrophoresis was used for characterization
      of keplerates in solution for the first time.

PMID- 25865041
TI  - Role of procalcitonin in diagnosis of bacterial infection in trans-arterial
      chemoembolisation treated hepatocellular carcinoma patients.
AB  - BACKGROUND AND STUDY AIM: Trans-arterial chemoembolisation (TACE) became the
      treatment of choice for multinodular hepatocellular carcinoma. The use of
      prophylactic antibiotics following intervention is controversial. This study
      aimed to assess the role of serum procalcitonin level in early diagnosis of
      bacterial infection following TACE to optimise antibiotic intake in those
      patients. PATIENTS AND METHODS: This study was carried on HCC patients diagnosed
      according to AASLD who underwent TACE and developed post interventional fever
      within 48 h. Laboratory investigations including CBC, neutrophil count, C
      reactive protein and ESR (pre and after intervention) were done. Cultures were
      done according to the suspected site of infection. Serum procalcitonin was done
      for all the included patients before and after TACE. RESULTS: Forty two TACE
      treated patients were included with post interventional fever within 48 h. Their
      ages ranged between 45 and 65 (mean 53.83 +/- 5.23). All patients received
      antibiotic prophylaxis started 24h pre intervention and for 5 days after
      according to the local protocol. Five patients (11.9%) had positive blood
      cultures post intervention. The analysis of laboratory results showed statistical
      significant correlation between procalcitonin levels and positive cultures, post
      interventional CRP and TLC and pre interventional INR and bilirubin, while there
      was statistical significant correlation between CRP and post interventional
      temperature, total leucocytic count and site of focal lesion. CONCLUSION:
      Procalcitonin seems to be a promising marker for diagnosis of sepsis in TACE
      treated HCC patients to optimise the unnecessary use of antibiotics.

PMID- 25865042
TI  - Proposal of inducible skin-associated lymphoid tissue (iSALT).
AB  - In the 1980s, Streilein et al. introduced the term 'skinassociated lymphoid
      tissue (SALT)' based on observations that revealed the existence of T cells and
      dendritic cells (DCs) in the skin and that T cells are activated in the skin
      draining lymph nodes. However, in the perspective of SALT, it remains still
      unclear whether and how cellular components in the skin interact with each other.
      In addition, whether the T-cell activation occurs in the skin in situ has also
      been unrevealed. With the close observation of a skin specimen obtained from a
      patient with contact dermatitis, we discovered that dermal DCs (dDCs) clustered
      and closely attached to T cells. Thus, we hypothesized that this clustering might
      be essential for the establishment of the dermatitis and the T-cell activation in
      situ. Through the detailed examination of the elicitation phase of contact
      hypersensitivity as a murine model of contact dermatitis, we demonstrated the
      formation of sequential leukocyte clusters at the postcapillary venules. The
      clusters include perivascular macrophages that are activated by IL-1a produced by
      keratinocytes and dDCs that are attracted by these macrophages through CXCL2
      signalling, both of which are essential for the efficient activation of memory T
      cells in situ. The structure does not exist in the steady state, but is 'induced'
      in response to local inflammatory conditions. Herein, we propose that this
      structure to be termed as 'inducible SALT (iSALT)'.

PMID- 25865043
TI  - Mechanical Stress Promotes Maturation of Human Myocardium From Pluripotent Stem
      Cell-Derived Progenitors.
AB  - Recent advances in pluripotent stem cell biology and directed differentiation
      have identified a population of human cardiovascular progenitors that give rise
      to cardiomyocytes, smooth muscle, and endothelial cells. Because the heart
      develops from progenitors in 3D under constant mechanical load, we sought to test
      the effects of a 3D microenvironment and mechanical stress on differentiation and
      maturation of human cardiovascular progenitors into myocardial tissue.
      Progenitors were derived from embryonic stem cells, cast into collagen hydrogels,
      and left unstressed or subjected to static or cyclic mechanical stress. Compared
      to 2D culture, the unstressed 3D environment increased cardiomyocyte numbers and
      decreased smooth muscle numbers. Additionally, 3D culture suppressed smooth
      muscle alpha-actin content, suggesting diminished cell maturation. Cyclic stress
      conditioning increased expression of several cardiac markers, including beta
      myosin heavy chain and cardiac troponin T, and the tissue showed enhanced calcium
      dynamics and force production. There was no effect of mechanical loading on
      cardiomyocyte or smooth muscle specification. Thus, 3D growth conditions favor
      cardiac differentiation from cardiovascular progenitors, whereas 2D conditions
      promote smooth muscle differentiation. Mechanical loading promotes cardiomyocyte
      structural and functional maturation. Culture in 3-D facilitates understanding
      how cues such as mechanical stress affect the differentiation and morphogenesis
      of distinct cardiovascular cell populations into organized, functional human
      cardiovascular tissue. Stem Cells 2015;33:2148-2157. 

PMID- 25865044
TI  - Icaritin suppresses multiple myeloma, by inhibiting IL-6/JAK2/STAT3.
AB  - Icaritin is an active prenylflavonoid derived from Epimedium genus, a traditional
      Chinese medicine. Icaritin has a wide range of pharmacological and biological
      activities, including cardiovascular function improvement, hormone regulation and
      antitumor activity. Here, we investigated the effect of icaritin on multiple
      myeloma (MM) in vitro and in vivo. Icaritin inhibited cell growth of MM cell line
      and primary MM cells. In contrast, icaritin had low or no cytotoxic effect on
      normal hematopoiesis. We also demonstrated that in MM xenograft mouse models,
      icaritin suppressed tumor growth and decreased serum IL-6 and IgE levels, but did
      not show adverse reactions such as body weight loss. The anti-MM activity of
      icaritin was mainly mediated by inhibiting IL-6/JAK2/STAT3 signaling. We suggest
      that icaritin can be further tested in clinical trials in MM. 

PMID- 25865045
TI  - An acyltransferase domain of FK506 polyketide synthase recognizing both an acyl
      carrier protein and coenzyme A as acyl donors to transfer allylmalonyl and
      ethylmalonyl units.
AB  - Acyltransferase (AT) domains of polyketide synthases (PKSs) usually use coenzyme
      A (CoA) as an acyl donor to transfer common acyl units to acyl carrier protein
      (ACP) domains, initiating incorporation of acyl units into polyketides. Two
      clinical immunosuppressive agents, FK506 and FK520, are biosynthesized by the
      same PKSs in several Streptomyces strains. In this study, characterization of
      AT4FkbB (the AT domain of the fourth module of FK506 PKS) in transacylation
      reactions showed that AT4FkbB recognizes both an ACP domain (ACPT csA) and CoA as
      acyl donors for transfer of a unique allylmalonyl (AM) unit to an acyl acceptor
      ACP domain (ACP4FkbB), resulting in FK506 production. In addition, AT4FkbB uses
      CoA as an acyl donor to transfer an unusual ethylmalonyl (EM) unit to ACP4FkbB,
      resulting in FK520 production, and transfers AM units to non-native ACP
      acceptors. Characterization of AT4FkbB in self-acylation reactions suggests that
      AT4FkbB controls acyl unit specificity in transacylation reactions but not in
      self-acylation reactions. Generally, AT domains of PKSs only recognize one acyl
      donor; however, we report here that AT4FkbB recognizes two acyl donors for the
      transfer of different acyl units. DATABASE: Nucleotide sequence data have been
      submitted to the GenBank database under accession numbers KJ000382 and KJ000383.

PMID- 25865046
TI  - A Hereditary Form of Small Intestinal Carcinoid Associated With a Germline
      Mutation in Inositol Polyphosphate Multikinase.
AB  - BACKGROUND & AIMS: Small intestinal carcinoids are rare and difficult to diagnose
      and patients often present with advanced incurable disease. Although the disease
      occurs sporadically, there have been reports of family clusters. Hereditary small
      intestinal carcinoid has not been recognized and genetic factors have not been
      identified. We performed a genetic analysis of families with small intestinal
      carcinoids to establish a hereditary basis and find genes that might cause this
      cancer. METHODS: We performed a prospective study of 33 families with at least 2
      cases of small intestinal carcinoids. Affected members were characterized
      clinically and asymptomatic relatives were screened and underwent exploratory
      laparotomy for suspected tumors. Disease-associated mutations were sought using
      linkage analysis, whole-exome sequencing, and copy number analyses of germline
      and tumor DNA collected from members of a single large family. We assessed
      expression of mutant protein, protein activity, and regulation of apoptosis and
      senescence in lymphoblasts derived from the cases. RESULTS: Familial and sporadic
      carcinoids are clinically indistinguishable except for the multiple synchronous
      primary tumors observed in most familial cases. Nearly 34% of asymptomatic
      relatives older than age 50 were found to have occult tumors; the tumors were
      cleared surgically from 87% of these individuals (20 of 23). Linkage analysis and
      whole-exome sequencing identified a germline 4-bp deletion in the gene inositol
      polyphosphate multikinase (IPMK), which truncates the protein. This mutation was
      detected in all 11 individuals with small intestinal carcinoids and in 17 of 35
      family members whose carcinoid status was unknown. Mutant IPMK had reduced kinase
      activity and nuclear localization, compared with the full-length protein. This
      reduced activation of p53 and increased cell survival. CONCLUSIONS: We found that
      small intestinal carcinoids can occur as an inherited autosomal-dominant disease.
      The familial form is characterized by multiple synchronous primary tumors, which
      might account for 22%-35% of cases previously considered sporadic. Relatives of
      patients with familial carcinoids should be screened to detect curable early
      stage disease. IPMK haploinsufficiency promotes carcinoid tumorigenesis.

PMID- 25865047
TI  - Platelet-Derived Growth Factor Receptor-alpha Regulates Proliferation of
      Gastrointestinal Stromal Tumor Cells With Mutations in KIT by Stabilizing ETV1.
AB  - BACKGROUND & AIMS: In gastrointestinal muscles, v-kit Hardy-Zuckerman 4 feline
      sarcoma viral oncogene homolog (KIT) is predominantly expressed by interstitial
      cells of Cajal (ICC) and platelet-derived growth factor receptor-alpha (PDGFRA)
      polypeptide is expressed by so-called fibroblast-like cells. KIT and PDGFRA have
      been reported to be coexpressed in ICC precursors and gastrointestinal stromal
      tumors (GISTs), which originate from the ICC lineage. PDGFRA signaling has been
      proposed to stimulate growth of GISTs that express mutant KIT, but the effects
      and mechanisms of selective blockade of PDGFRA are unclear. We investigated
      whether inhibiting PDGFRA could reduce proliferation of GIST cells with mutant
      KIT via effects on the KIT-dependent transcription factor ETV1. METHODS: We
      studied 53 gastric, small intestinal, rectal, or abdominal GISTs collected
      immediately after surgery or archived as fixed blocks at the Mayo Clinic and
      University of California, San Diego. In human GIST cells carrying imatinib
      sensitive and imatinib-resistant mutations in KIT, PDGFRA was reduced by RNA
      interference (knockdown) or inhibited with crenolanib besylate (a selective
      inhibitor of PDGFRA and PDGFRB). Mouse ICC precursors were retrovirally
      transduced to overexpress wild-type Kit. Cell proliferation was analyzed by
      methyltetrazolium, 5-ethynyl-2'-deoxyuridine incorporation, and Ki-67
      immunofluorescence assays; we also analyzed growth of xenograft tumors in mice.
      Gastric ICC and ICC precursors, and their PDGFRA(+) subsets, were analyzed by
      flow cytometry and immunohistochemistry in wild-type, Kit(+/copGFP),
      Pdgfra(+/eGFP), and NOD/ShiLtJ mice. Immunoblots were used to quantify protein
      expression and phosphorylation. RESULTS: KIT and PDGFRA were coexpressed in 3%-5%
      of mouse ICC, 35%-44% of ICC precursors, and most human GIST samples and cell
      lines. PDGFRA knockdown or inhibition with crenolanib efficiently reduced
      proliferation of imatinib-sensitive and imatinib-resistant KIT(+)ETV1(+)PDGFRA(+)
      GIST cells (50% maximal inhibitory concentration = 5-32 nM), but not of cells
      lacking KIT, ETV1, or PDGFRA (50% maximal inhibitory concentration >230 nM).
      Crenolanib inhibited phosphorylation of PDGFRA and PDGFRB, but not KIT. However,
      Kit overexpression sensitized mouse ICC precursors to crenolanib. ETV1 knockdown
      reduced KIT expression and GIST proliferation. Crenolanib down-regulated ETV1 by
      inhibiting extracellular-signal-regulated kinase (ERK)-dependent stabilization of
      ETV1 protein and also reduced expression of KIT and PDGFRA. CONCLUSIONS: In KIT
      mutant GIST, inhibition of PDGFRA disrupts a KIT-ERK-ETV1-KIT signaling loop by
      inhibiting ERK activation. The PDGFRA inhibitor crenolanib might be used to treat
      patients with imatinib-resistant, KIT-mutant GIST.

PMID- 25865049
TI  - Weight Loss Through Lifestyle Modification Significantly Reduces Features of
      Nonalcoholic Steatohepatitis.
AB  - BACKGROUND & AIMS: It is not clear how weight loss affects histologic features of
      liver in patients with nonalcoholic steatohepatitis (NASH). We examined the
      association between the magnitude of weight loss through lifestyle modifications
      and changes in histologic features of NASH. METHODS: We conducted a prospective
      study of 293 patients with histologically proven NASH who were encouraged to
      adopt recommended lifestyle changes to reduce their weight over 52 weeks, from
      June 2009 through May 2013, at a tertiary medical center in Havana, Cuba. Liver
      biopsies were collected when the study began and at week 52 of the diet and were
      analyzed histologically. RESULTS: Paired liver biopsies were available from 261
      patients. Among 293 patients who underwent lifestyle changes for 52 weeks, 72
      (25%) achieved resolution of steatohepatitis, 138 (47%) had reductions in
      nonalcoholic fatty liver disease activity score (NAS), and 56 (19%) had
      regression of fibrosis. At week fifty-two, 88 subjects (30%) had lost >=5% of
      their weight. Degree of weight loss was independently associated with
      improvements in all NASH-related histologic parameters (odds ratios = 1.1-2.0; P
      < .01). A higher proportion of subjects with >=5% weight loss had NASH resolution
      (51 of 88 [58%]) and a 2-point reduction in NAS (72 of 88 [82%]) than subjects
      who lost <5% of their weight (P < .001). All patients who lost >=10% of their
      weight had reductions NAS, 90% had resolution of NASH, and 45% had regression of
      fibrosis. All patients who lost 7%-10% of their weight and had few risk factors
      also had reduced NAS. In patients with baseline characteristics that included
      female sex, body mass index >=35, fasting glucose >5.5 mmol/L, and many ballooned
      cells, NAS scores decreased significantly with weight reductions >=10%.
      CONCLUSIONS: A greater extent of weight loss, induced by lifestyle changes, is
      associated with the level of improvement in histologic features of NASH. The
      highest rates of NAS reduction, NASH resolution, and fibrosis regression occurred
      in patients with weight losses >=10%.

PMID- 25865050
TI  - The effect of Oral Rehydration Solution on apoptosis of periodontal ligament
      cells.
AB  - BACKGROUND: Over the years, numerous studies have been conducted to find a
      storage medium with favorable properties to preserve the avulsed teeth. Oral
      Rehydration Solution (ORS) is a simple oral solution containing glucose and
      electrolytes. In addition to physiologic PH and osmolality, it has other
      important properties such as availability and inexpensiveness, storing potential
      in different conditions and places, and long lifetime. This study was carried out
      to more precisely investigate the storage of cells in this substance in different
      concentrations and in longer times, and to evaluate the programmed cell death or
      apoptosis as well as cell viability. MATERIAL AND METHODS: The cultured PDL cells
      of this experimental study were exposed to three concentrations of 25%, 50%, and
      100% ORS in comparison with Hanks Balanced Salt Solution (HBSS) and tap water.
      They were then analyzed by Tetrazolium Salt-based Colorimetric (MTT) Assay in 2-,
      6-, 12-, 24-, and 48-h periods and by Apoptosis Assay in 12-, 24-, and 48-h time
      periods. Data were analyzed by spss software using anova and Post hoc (Duncan)
      tests. P <= 0.05 was considered significant. RESULTS: Overall, the maximum viable
      cells and minimum apoptotic cells were reported after the cells' exposure to ORS
      (100%). Also, the minimum level of viable cells was observed in ORS (25%) group
      and the highest level of apoptotic cells was observed in 25% and 50% ORS groups.
      CONCLUSION: ORS preserved more viable cells and induced fewer apoptotic cells in
      comparison with HBSS.

PMID- 25865048
TI  - Inhibiting Inducible Nitric Oxide Synthase in Enteric Glia Restores Electrogenic
      Ion Transport in Mice With Colitis.
AB  - BACKGROUND & AIMS: Disturbances in the control of ion transport lead to
      epithelial barrier dysfunction in patients with colitis. Enteric glia regulate
      intestinal barrier function and colonic ion transport. However, it is not clear
      whether enteric glia are involved in epithelial hyporesponsiveness. We
      investigated enteric glial regulation of ion transport in mice with
      trinitrobenzene sulfonic acid- or dextran sodium sulfate-induced colitis and in
      Il10(-/-) mice. METHODS: Electrically evoked ion transport was measured in full
      thickness segments of colon from CD1 and Il10(-/-) mice with or without colitis
      in Ussing chambers. Nitric oxide (NO) production was assessed using amperometry.
      Bacterial translocation was investigated in the liver, spleen, and blood of mice.
      RESULTS: Electrical stimulation of the colon evoked a tetrodotoxin-sensitive
      chloride secretion. In mice with colitis, ion transport almost completely
      disappeared. Inhibiting inducible NO synthase (NOS2), but not neuronal NOS
      (NOS1), partially restored the evoked secretory response. Blocking glial function
      with fluoroacetate, which is not a NOS2 inhibitor, also partially restored ion
      transport. Combined NOS2 inhibition and fluoroacetate administration fully
      restored secretion. Epithelial responsiveness to vasoactive intestinal peptide
      was increased after enteric glial function was blocked in mice with colitis. In
      colons of mice without colitis, NO was produced in the myenteric plexus almost
      completely via NOS1. NO production was increased in mice with colitis, compared
      with mice without colitis; a substantial proportion of NOS2 was blocked by
      fluoroacetate administration. Inhibition of enteric glial function in vivo
      reduced the severity of trinitrobenzene sulfonic acid-induced colitis and
      associated bacterial translocation. CONCLUSIONS: Increased production of NOS2 in
      enteric glia contributes to the dysregulation of intestinal ion transport in mice
      with colitis. Blocking enteric glial function in these mice restores epithelial
      barrier function and reduces bacterial translocation.

PMID- 25865051
TI  - Prescription of oral anticoagulation for patients with atrial fibrillation and
      previous hospitalization in a cardiology department. Experience in actual
      practice in a tertiary hospital.
AB  - INTRODUCTION: Atrial fibrillation is the main reason for oral anticoagulation in
      our community. New oral anticoagulants (NOACs) overcome the disadvantages of
      vitamin K antagonists (VKAs), although there are scarce data on its use in our
      community. The aim of our study was to assess the use of NOACs and
      anticoagulation control using VKA as measured by the time within the therapeutic
      range (TTR) in an actual clinical scenario. METHODS: A retrospective cohort
      analysis was conducted of 816 patients admitted to cardiology over a period of 3
      years, with a diagnosis of atrial fibrillation and anticoagulant treatment at
      discharge. We assessed the percentage of patients prescribed NOACs and the TTR
      with VKA. We compared safety and efficacy events during the 15-month follow-up
      among the patients prescribed NOAC, those prescribed VKA with a good TTR and
      those with a poor TTR. RESULTS: The percentage of patients prescribed NOAC was
      7.6%. Serial INR measurements found that 71.3% of patients had a poor TTR.
      Although the groups were not comparable, a higher incidence of the combined event
      was observed in those treated with VKA and a poor TTR compared with those
      prescribed NOAC (p=.01). CONCLUSIONS: For patients with a previous
      hospitalization in cardiology in a tertiary hospital and a diagnosis of atrial
      fibrillation, the rate of NOAC prescription is low, and the TTR with VKA was
      poor.

PMID- 25865052
TI  - Subacute back pain.

PMID- 25865053
TI  - Infectious Spondylitis: 30 Years Later, problems persist. Should we change the
      approach?

PMID- 25865055
TI  - Growth, immune responses and intestinal morphology of rainbow trout (Oncorhynchus
      mykiss) supplemented with commercial probiotics.
AB  - The influence of two commercial probiotics on the growth, innate immune
      parameters and intestinal morphology of rainbow trout (Oncorhynchus mykiss)
      juveniles (initial weight: 16.4 +/- 0.4 g) was evaluated. Two probiotic types: A,
      multi-species (Bacillus sp., Pedicoccus sp., Enterococcus sp., Lactobacillus sp.)
      and B, mono-species (Pediococcus acidilactici) were tested at two levels each
      (A1: 1.5 g kg(-1), 8.6 * 10(5) CFU g(-1); A2: 3 g kg(-1), 1.6 * 10(6) CFU g(-1);
      B1: 0.1 g kg(-1), 2.6 * 10(4) CFU g(-1); B2: 0.2 g kg(-1), 7.2 * 10(4) CFU g(-1))
      versus an unsupplemented diet (C). Diets were distributed to sextuplicate tanks,
      three times a day to visual satiation for 8 weeks. Growth performance and immune
      responses (plasma lysozyme, ACH50, peroxidase and head kidney respiratory burst)
      were determined at 4 and 8 weeks of feeding. Body composition and intestine
      morphology were determined at the end of the feeding trial. At 8 weeks, the lower
      dose of multi-species probiotic (A1) improved growth rate, while both probiotic
      types improved feed conversion rate compared to the control animals, at the lower
      dose of multi-species (A1) and at the higher dose of mono-species (B2)
      probiotics. Body composition did not vary between treatments. At 4 weeks, ACH50
      activity was significantly higher in fish fed higher dose of B probiotic (B2,
      123.7 +/- 50.6 vs 44.1 +/- 7.7 U.ml(-1) in control). At 8 weeks, lysozyme
      activity was higher in fish fed A1 (13.1 +/- 5.2 MUg ml(-1)) diet compared to
      fish fed control diet (7.8 +/- 1 MUg ml(-1)). Plasma peroxidase and head-kidney
      respiratory burst did not differ among the dietary treatments. Villi length and
      integrity and goblet cell counting of a cross section of the anterior intestine
      were not significantly different between groups. Results suggest benefits in
      zootechnical performance and immune humoral responses using both probiotic types,
      in a dose dependent manner, without apparent alterations in intestinal
      morphology.

PMID- 25865054
TI  - Mechanisms of nanosilver-induced toxicological effects: more attention should be
      paid to its sublethal effects.
AB  - Due to its unique physicochemical properties and remarkable antimicrobial
      activity, nanosilver (nAg) is increasingly being used in a wide array of fields,
      including medicine and personal care products. Despite substantial progress being
      made towards the understanding of the acute toxicity of nAg, large knowledge gaps
      still exist on the assessment of its chronic toxicity to humans. Chronic effects
      of nAg, typically at low doses (i.e. sublethal doses) should be different from
      the acute toxicity at high doses (i.e., lethal doses), which is analogous to
      other environmental pollutants. Although a few review papers have elaborated the
      findings on nAg-mediated toxicity, most of them only discussed overt toxicity of
      nAg at high-level exposure and failed to evaluate the chronic and cumulative
      effects of nAg at sublethal doses. Therefore, it is necessary to more stringently
      scrutinize the sublethal toxicity of nAg under environmentally relevant
      conditions. Herein, we recapitulated recent findings on the sublethal effects of
      nAg toxicity performed by our groups and others. We then discussed the molecular
      mechanisms by which nAg exerts its toxicity under low concentrations and compared
      that with nAg-induced cell death. 

PMID- 25865056
TI  - Limonium sinense and gallic acid suppress hepatitis C virus infection by blocking
      early viral entry.
AB  - A preventive vaccine against hepatitis C virus (HCV) infection remains
      unavailable and newly developed drugs against viral replication are complicated
      by potential drug-resistance and high cost. These issues justify the need to
      develop alternative antiviral agents and expand the scope of strategies for the
      treatment of hepatitis C, such as targeting viral entry. In this study, we
      explore the bioactivity of Limonium sinense (L. sinense) and its purified
      constituents against HCV life cycle using subgenomic replicon and infectious HCV
      culture systems. Data indicated that the water extract from the underground part
      of L. sinense (LS-UW) exhibited potent inhibitory activity against HCV at non
      cytotoxic concentrations. LS-UW targeted early HCV infection without affecting
      viral replication, translation, and cell-to-cell transmission, and blocked viral
      attachment and post-attachment entry/fusion steps. Bioactivity analysis of major
      constituents from LS-UW through viral infectivity/entry assays revealed that
      gallic acid (GA) also inhibits HCV entry. Furthermore, both LS-UW and GA could
      suppress HCV infection of primary human hepatocytes. Due to their potency and
      ability to target HCV early viral entry, LS-UW and GA may be of value for further
      development as prospective antivirals against HCV. 

PMID- 25865057
TI  - Association Between Self-Reported Bruxism and Malocclusion in University
      Students: A Cross-Sectional Study.
AB  - OBJECTIVES: Bruxism can result in temporomandibular disorders, oral pain, and
      tooth wear. However, it is unclear whether bruxism affects malocclusion. The aim
      of this study was to examine the association between self-reported bruxism and
      malocclusion in university students. METHODS: Students (n = 1503; 896 men and 607
      women) aged 18 and 19 years were examined. Malocclusion was defined using a
      modified version of the Index of Orthodontic Treatment Need. The presence of
      buccal mucosa ridging, tooth wear, dental impression on the tongue,
      palatal/mandibular torus, and the number of teeth present were recorded, as well
      as body mass index (BMI). Additional information regarding gender, awareness of
      bruxism, orthodontic treatment, and oral habits was collected via questionnaire.
      RESULTS: The proportion of students with malocclusion was 32% (n = 481). The
      awareness of clenching in males with malocclusion was significantly higher than
      in those with normal occlusion (chi square test, P < 0.01). According to logistic
      regression analysis, the probability of malocclusion was significantly associated
      with awareness of clenching (odds ratio [OR] 2.19; 95% confidence interval [CI],
      1.22-3.93) and underweight (BMI <18.5 kg/m(2)) (OR 1.89; 95% CI, 1.31-2.71) in
      males but not in females. In subgroup analyses, the probability of crowding was
      also significantly associated with awareness of clenching and underweight (P <
      0.01) in males. CONCLUSIONS: Awareness of clenching and underweight were related
      to malocclusion (crowding) in university male students.

PMID- 25865058
TI  - The role of life events and psychological factors in the onset of first and
      recurrent mood episodes in bipolar offspring: results from the Dutch Bipolar
      Offspring Study.
AB  - BACKGROUND: Life events are an established risk factor for the onset and
      recurrence of unipolar and bipolar mood episodes, especially in the presence of
      genetic vulnerability. The dynamic interplay between life events and
      psychological context, however, is less studied. In this study, we investigated
      the impact of life events on the onset and recurrence of mood episodes in bipolar
      offspring, as well as the effects of temperament, coping and parenting style on
      this association. METHOD: Bipolar offspring (n = 108) were followed
      longitudinally from adolescence to adulthood. Mood disorders were assessed with:
      the Kiddie Schedule of Affective Disorders and Schizophrenia - Present and
      Lifetime Version or the Structured Clinical Interview for DSM-IV Axis I
      disorders; life events with the Life Events and Difficulties Schedule; and
      psychological measures using the Utrecht Coping List, Temperament and Character
      Inventory and short-EMBU (memories of upbringing instrument). Anderson-Gill
      models (an extension of the Cox proportional hazard model) were utilized.
      RESULTS: Life events were associated with an increased risk for first and,
      although less pronounced, subsequent mood episodes. There was a large confounding
      effect for the number of previous mood episodes; findings suggest a possible
      kindling effect. Passive coping style increased the risk of mood episode onset
      and recurrent episodes, but also altered the effect of life events on mood
      disorders. Harm avoidance temperament was associated with mood episode
      recurrence. CONCLUSIONS: Life events are especially a risk factor in the onset of
      mood disorders, though less so in recurrent episodes. Psychological features
      (passive coping and harm-avoidant temperament) contribute to the risk of an
      episode occurring, and also have a moderating effect on the association between
      life events and mood episodes. These findings create potential early intervention
      strategies for bipolar offspring.

PMID- 25865059
TI  - Arsenic Speciation in Honeysuckle (Lonicera japonica Thunb.) from China.
AB  - In this study, honeysuckle, a common Chinese herbal medicine, produced from
      different areas was investigated for total arsenic and arsenic species
      concentration. The total arsenic concentrations were determined by inductively
      coupled plasma mass spectrometry (ICP-MS) and ranged from 275 to 635 MUg kg(-1).
      A microwave-assisted procedure with 1 % phosphoric acid (v/v) was used for the
      extraction of arsenic species in honeysuckle. The total arsenic species
      concentration found by liquid chromatography-inductively coupled plasma mass
      spectrometry (LC-ICP-MS) was in agreement with the total arsenic concentration
      determined by the ICP-MS analysis after the microwave digestion. Arsenate (As(V))
      with an average proportion of 54.3 % was the predominant arsenic species in
      honeysuckle. The order of concentration is as follows: As(V) > arsenite (As(III))
      > dimethylarsinic acid (DMA) > arsenobetaine (AsB) > monomethylarsonic acid
      (MMA). The proportion of organic arsenic (24.7 %) was higher than that in most
      terrestrial plants. Moreover, the distributions of arsenic species in the
      honeysuckle from different producing areas were significantly different. This
      study provides useful information for better understanding of the distribution of
      arsenic species in terrestrial plants. 

PMID- 25865060
TI  - Re: Arun A. Azad, Bernhard J. Eigl, Raya Leibowitz-Amit, et al. Outcomes with
      abiraterone acetate in metastatic castration-resistant prostate cancer patients
      who have poor performance status. Eur Urol 2015;67:441-7.

PMID- 25865061
TI  - Natural History of Clinical Recurrence Patterns of Lymph Node-Positive Prostate
      Cancer After Radical Prostatectomy.
AB  - BACKGROUND: Patients with lymph node (LN)-positive prostate cancer (PCa) at
      radical prostatectomy (RP) face a high risk of cancer recurrence. Nevertheless,
      recurrence patterns of LN-positive PCa and their prognostic significance remain
      understudied in the literature. OBJECTIVE: To analyze a large single-institution
      series with long-term follow-up to elucidate the various clinical recurrence
      patterns of LN-positive PCa and their association with oncologic outcomes.
      DESIGN, SETTING, AND PARTICIPANTS: Years 1987-2012 of a prospectively maintained
      institutional RP registry were queried for men with LN-positive PCa at RP.
      Clinical recurrences were categorized as local, nodal, skeletal, or visceral.
      OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: In addition to descriptive
      statistics and Kaplan-Meier analysis, univariable and multivariable Cox
      proportional hazards models were constructed to predict recurrence and to
      quantify the impact of recurrence patterns on cancer-specific mortality (CSM).
      RESULTS AND LIMITATIONS: Data from 1011 men with LN-positive PCa at RP were
      analyzed with 17.6 yr of median follow-up. The 15-yr clinical recurrence rate was
      33% (95% confidence interval [CI], 31-35%) for all patients and 52.2% (95% CI,
      47.3-57.1%) for patients with biochemical recurrence. The solitary locations were
      skeletal (n=94, 55%), nodal (n=59, 34%), local soft tissue (n=29, 17%), and
      visceral (n=8, 5%). Significant multivariable predictors of recurrence were
      Gleason score 8-10, number of positive nodes, pathologic Gleason score, and more
      recent year of surgery. The 15-yr CSM after clinical recurrence was 80%, with a
      mean overall survival of 30 mo after recurrence. On multivariable analysis,
      recurrences after 5 yr from RP (hazard ratio [HR]: 0.05), multiple recurrences
      (HR: 1.97), skeletal (HR: 3.13), and visceral metastases (HR: 7.43) were
      independently associated with CSM (all p<0.05). CONCLUSIONS: Recurrences after RP
      for LN-positive PCa are heterogeneous in terms of time from RP, location, and
      number of concomitant lesions. PATIENT SUMMARY: We found that impact of
      recurrence patterns on cancer-specific mortality varies significantly and allows
      these patients to be stratified for purposes of prognostication, follow-up, and
      therapy.

PMID- 25865062
TI  - A review of behaviour change theories and techniques used in group based self
      management programmes for chronic low back pain and arthritis.
AB  - BACKGROUND: Medical Research Council (MRC) guidelines recommend applying theory
      within complex interventions to explain how behaviour change occurs. Guidelines
      endorse self-management of chronic low back pain (CLBP) and osteoarthritis (OA),
      but evidence for its effectiveness is weak. OBJECTIVE: This literature review
      aimed to determine the use of behaviour change theory and techniques within
      randomised controlled trials of group-based self-management programmes for
      chronic musculoskeletal pain, specifically CLBP and OA. METHODS: A two-phase
      search strategy of electronic databases was used to identify systematic reviews
      and studies relevant to this area. Articles were coded for their use of behaviour
      change theory, and the number of behaviour change techniques (BCTs) was
      identified using a 93-item taxonomy, Taxonomy (v1). RESULTS: 25 articles of 22
      studies met the inclusion criteria, of which only three reported having based
      their intervention on theory, and all used Social Cognitive Theory. A total of 33
      BCTs were coded across all articles with the most commonly identified techniques
      being 'instruction on how to perform the behaviour', 'demonstration of the
      behaviour', 'behavioural practice', 'credible source', 'graded tasks' and 'body
      changes'. CONCLUSION: Results demonstrate that theoretically driven research
      within group based self-management programmes for chronic musculoskeletal pain is
      lacking, or is poorly reported. Future research that follows recommended
      guidelines regarding the use of theory in study design and reporting is
      warranted.

PMID- 25865063
TI  - Integrating phylogeography and paleoecology to investigate the origin and
      dynamics of hybrid zones: insights from two widespread North American firs.
AB  - Secondary contact between closely related taxa routinely occurs during
      postglacial migrations. After initial contact, the location of hybrid zones may
      shift geographically or remain spatially stable over time in response to various
      selective pressures or neutral processes. Studying the extent and direction of
      introgression using markers having contrasted levels of gene flow can help
      unravel the historical dynamics of hybrid zones. Thanks to their contrasted
      maternal and paternal inheritance, resulting in different levels of gene flow for
      mitochondrial and chloroplast DNA (mtDNA and cpDNA), the Pinaceae stand out as a
      relevant biological model for this purpose. The objective of the study was to
      assess whether the hybrid zone between Abies balsamea and Abies lasiocarpa (two
      largely distributed Pinaceae) has moved or remained stable over time by analysing
      the distribution of cytoplasmic DNA variation as well as published
      palaeobotanical data. Interspecific gene flow was higher for cpDNA than mtDNA
      markers; hence, the geographic distribution of mitotypes was more congruent with
      species distributions than chlorotypes. This genetic signature was contrary to
      expectations under a moving hybrid zone scenario, as well as empirical
      observations in other conifers. Genetic evidence for this rare instance of stable
      hybrid zone was corroborated by the colonization chronology derived from
      published fossil data, indicating that the two fir species initially came into
      contact in the area corresponding to the current sympatric zone 11 kyr ago. While
      an explanatory analysis suggested the putative influence of various environmental
      factors on the relative abundance of cytoplasmic genome combinations, further
      research appears necessary to assess the role of both demographic history and
      selective factors in driving the dynamics of hybrid zones. 

PMID- 25865064
TI  - TIRADS for sonographic assessment of hypofunctioning and indifferent thyroid
      nodules.
AB  - AIM: To test the feasibility of the Thyroid Imaging Reporting And Data System
      (TIRADS) according to Horvath and Kwak for the assessment of thyroid nodules.
      PATIENTS, METHOD: Retrospective analysis of patients with thyroid nodules
      applying the following inclusion criteria: B-mode-ultrasound, surgery and
      histological results. Thyroid nodules were classified as TIRADS 2, 3, 4A, 4B, 4C,
      5 and 6. RESULTS: A total of 172 patients were included (133 women, 48 +/- 13
      years, 39 men, 49 +/- 11 years) with 222 thyroid nodules (24.9 +/- 11.5 mm).
      Final histological diagnosis revealed 203 benign nodules (91%) and 19 malignant
      nodules (9%; 18 papillary thyroid carcinoma, PTC, and one medullary thyroid
      carcinoma, MTC). One hundred and sixty thyroid nodules were hypofunctioning in
      99mTc-pertechnetate-scintigraphy, 14 nodules were hyperfunctioning and 46 nodules
      were classified as indifferent. In two cases with small carcinoma < 1 cm 99mTc
      pertechnetate-scintigraphy was not performed. According to Horvath, the
      prevalence of malignancy was 6.7% in TIRADS 2, 0% in 3, 1.9% in 4A, 33% in 4B,
      12.5% in 5 and 100% in 6; 73 nodules (39%) were not clearly classifiable,
      including 3 carcinoma (4.1%). According to Kwak, the prevalence of malignancy was
      6.9% in TIRADS 2, 0% in 3, 2% in 4A, 4.1% in 4B, 23.1% in 4C, and 100% in 5 and
      6, respectively. Notably, in the subgroup of hot nodules, 11 (79%) were graded as
      TIRADS 4A or higher, and thus advisable for fine-needle aspiration biopsy in both
      TIRADS. CONCLUSION: The TIRADS described by Horvath is not practicable due to
      numerous unclassifiable nodules. The revised TIRADS published by Kwak is feasible
      and suitable to assess the prevalence of malignancy, but it cannot replace
      scintigraphic imaging. Fine-needle-biopsy is not necessary in nodules categorized
      as (K)TIRADS 3, 4A and 5.

PMID- 25865065
TI  - The acetyltransferase HAT1 moderates the NF-kappaB response by regulating the
      transcription factor PLZF.
AB  - To date, the activities of protein kinases have formed the core of our
      understanding of cell signal transduction. Comprehension of the extent of protein
      acetylation has raised expectations that this alternate post-transcriptional
      modification will be shown to rival phosphorylation in its importance in
      mediating cellular responses. However, limited instances have been identified.
      Here we show that signalling from Toll-like or TNF-alpha receptors triggers the
      calcium/calmodulin-dependent protein kinase (CaMK2) to activate histone
      acetyltransferase-1 (HAT1), which then acetylates the transcriptional regulator
      PLZF. Acetylation of PLZF promotes the assembly of a repressor complex
      incorporating HDAC3 and the NF-kappaB p50 subunit that limits the NF-kappaB
      response. Accordingly, diminishing the activity of CaMK2, the expression levels
      of PLZF or HAT1, or mutating key residues that are covalently modified in PLZF
      and HAT1, curtails control of the production of inflammatory cytokines. These
      results identify a central role for acetylation in controlling the inflammatory
      NF-kappaB transcriptional programme. 

PMID- 25865066
TI  - Nanoparticles-free fluorescence anisotropy amplification assay for detection of
      RNA nucleotide-cleaving DNAzyme activity.
AB  - Fluorescence anisotropy is a homogeneous, sensitive, ratiometric, and real-time
      analytical technology. However, it is a great challenge to produce a large
      fluorescence anisotropy change upon the presence of target small molecules
      without nanoparticles-dependent amplification. This work reports a nanoparticle
      free and multiple G-enhanced fluorescence anisotropy assay for detection of
      DNAzyme activity. A Pb(2+)-dependent GR-5 DNAzyme was used as a model. We
      hybridized the rA-cleavable substrate strand containing a TMR label at the 5'-end
      with the DNAzyme strand containing an extended three G bases at the 3'-end. By
      this design, we demonstrate that both fluorescence quenching and the enhanced
      DNAzyme activity contribute to a Pb(2+)-induced large fluorescence anisotropy
      change (|Deltar| = 0.168). The limit of detection for Pb(2+) is estimated to be
      about 100 pM with a dynamic range from 200 pM to 100 nM. The interference from
      the other nine divalent metal ions of 1000-times excess amount is negligible.
      Moreover, we show an extended assay for evaluation of the interactions of Pb(2+)
      with cysteine and glutathione by the detection of GR5 DNAzyme activity.
      Collectively, we developed a novel fluorescence anisotropy amplification assay,
      enabling us to detect DNAzyme activity and associated cofactors and inhibitors
      and to characterize the Pb(2+)-chelation capability of free thiols. 

PMID- 25865067
TI  - An outbreak of infections caused by extensively drug-resistant Klebsiella
      pneumoniae strains during a short period of time in a Chinese teaching hospital:
      epidemiology study and molecular characteristics.
AB  - In this study, we comprehensively described the clinical risk factors, outcome,
      epidemiology, and molecular basis associated with an outbreak of extensively drug
      resistant KPC-2-producing Klebsiella pneumoniae involving 15 patients in a
      teaching hospital from May 1 to June 27, 2013. Most of the patients were elderly
      and received long-term hospital treatment, and 40.0% (6/15) of them were dead.
      All strains carried bla(KPC-2), rmtB, bla(CTX-M-65), bla(SHV-11), oqxA, oqxB, and
      aac(6')-Ib-cr and even harbored additional other resistance genes, such as armA,
      bla(CTX-M-1), bla(TEM-1). bla(KPC-2), rmtB, and bla(CTX-M-65) were located on the
      same ~54.2-kb plasmid, and conjugation experiments further proved the
      cotransferable characteristic. Alterations of outer membrane proteins were
      confirmed by sodium dodecyl sulfate--olyacrylamide gelelectrophoresis and
      sequencing, which can lead to a drastic change in the permeability of cells. All
      isolates belonged to the clone complex 258, spreading rapidly across the world.
      Our study demonstrated that a high degree of awareness and surveillance of those
      drug resistance determinants is urgently needed.

PMID- 25865068
TI  - Oral health perception in veterans with self-identified disabilities: National
      Survey of Veterans, 2010.
AB  - OBJECTIVE: This study examines the relationship of self-identified disability and
      oral health perception in a veteran population. METHODS: The National Survey of
      Veterans, 2010, database was used to conduct a cross-sectional study of 8,303
      participants. Questionnaires were mailed to the veterans, and the questions were
      developed to assess sociodemographic information, health perception, and health
      status, among other areas of interest. The Andersen Behavioral Model was used as
      the framework for the study. The outcome of interest was perceived oral health,
      and the main variable of interest was self-identified disability. The data were
      analyzed for descriptive, and bivariate analyses, and logistic regression.
      RESULTS: There were 1,904 participants (21.2 percent) with self-identified
      disability. There were 2,505 participants (41.0 percent) who indicated negative
      oral health perception. In logistic regression, individuals with self-identified
      disability had an unadjusted odds ratio of 1.63 (95 percent CI: 1.44, 1.85) and
      an adjusted odds ratio of 1.69 (95 percent CI: 1.44, 1.99) for negative oral
      health perception as compared with participants who did not self-identify
      disability. CONCLUSION: Oral health perception in a veteran population is
      affected by predisposing and enabling factors among which is self-identified
      disability.

PMID- 25865069
TI  - Mitochondria-targeted fluorescent thermometer monitors intracellular temperature
      gradient.
AB  - Intracellular thermometry at the microscopic level is currently a hot topic.
      Herein we describe a small molecule fluorescent thermometer targeting
      mitochondria (Mito thermo yellow). Mito thermo yellow successfully demonstrates
      the ability to monitor the intracellular temperature gradient, generated by
      exogenous heating, in various cells. 

PMID- 25865070
TI  - INPPO2014, First INPPO World Congress on "Plant Proteomics: Methodology to
      Biology"-A global platform for involving, gathering and disseminating knowledge.
AB  - The International Plant Proteomics Organization (INPPO) is a global platform of
      the plant proteomics community or, more generally, the scientific community that
      uses proteomics to address plant biology. Organizing an international conference
      is one of its initiatives to promote plant proteomics by involving and gathering
      scientists/researchers/students and by disseminating the acquired knowledge. In
      this fourth INPPO Highlights, the first INPPO World Congress 2014 (INPPO2014) is
      described and discussed. The INPPO2014 was held at the University of Hamburg
      (Germany) with the title "Plant Proteomics: Methodology to Biology" under the
      leadership of Sabine Luthje (Germany). Participants (around 150) from 38 nations
      attended this congress covering all continents. The four-day scientific program
      comprised 52 lectures and 61 poster presentations in a highly professional and
      friendly atmosphere on mass spectrometry and gel-based proteomics. Two round
      table open discussions deliberated on plant proteomics, its associated
      international organizations/initiatives and future INPPO perspectives. The Second
      INPPO World Congress 2016 (INPPO2016) "The Quest for Tolerant Varieties
      Phenotyping at Plant and Cellular Level" is planned to be organized in Bratislava
      (Slovakia) under the leadership of Martin Hajduch (Slovak Republic) and Sebastien
      Carpentier (Belgium) and cosponsored by the COST action FA1306. 

PMID- 25865071
TI  - Imaging of cutaneous T-cell lymphomas by optical coherence tomography - a case
      series study.

PMID- 25865072
TI  - Radiopacity for Contemporary Luting Cements Using Digital Radiography under
      Various Exposure Conditions.
AB  - PURPOSE: This study examined the radiopacity of contemporary luting cements using
      direct digital radiography under a range of exposure conditions. MATERIALS AND
      METHODS: Disc specimens (N = 80, n = 10 per group, o5 mm * 1 mm) were prepared
      from 8 resin-based luting cements (BisCem Clearfil SA Luting, Duolink, Maxcem
      Elite Multilink Speed, Panavia F 2.0, RelyX Unicem Clicker, V-link). The
      specimens were radiographed using a charge-coupled device sensor along with an 11
      step aluminum step wedge (1.5-mm incremental steps) and 1-mm-thick tooth cut
      using five tube voltage/exposure time setups (60 kVp, 0.10/0.08 seconds; 70 kVp,
      0.10/0.08/0.06 seconds) at 4 mA and 30 cm. The radiopacity of the specimens was
      compared with that of the aluminum step wedge and human enamel and dentin using
      NIH ImageJ software (available at http://rsb.info.nih.gov/ij/). A linear
      regression model for the aluminum step wedge was constructed, and the data were
      analyzed by ANOVA and Duncan post hoc test. RESULTS: Maxcem Elite (5.142 to
      5.441) showed the highest radiopacity of all materials, followed in order by
      Multilink Speed (3.731 to 3.396) and V-link (2.763 to 3.103). The radiopacity of
      Panavia F 2.0 (2.025 to 2.429), BisCem (1.825 to 2.218), Clearfil SA Luting
      (1.692 to 2.145), Duolink (1.707 to 1.993), and RelyX Unicem Clicker (1.586 to
      1.979) were between enamel (2.117 to 2.330) and dentin (1.302 to 1.685). The
      radiopacity of 70 kVp conditions was higher than that of the 60 kVp conditions.
      CONCLUSIONS: The radiopacities of the tested luting materials were greater than
      those of dentin or aluminum, satisfying the criteria of the International
      Organization for Standardization, and they differed significantly from each other
      in the exposure setups.

PMID- 25865073
TI  - Autophagy potentially protects against 2,3,7,8-tetrachlorodibenzo-p-Dioxin
      induced apoptosis in SH-SY5Y cells.
AB  - The environmental toxicant TCDD may elicit cytotoxic effects by inducing reactive
      oxygen species (ROS) generation. Autophagy is one of the first lines of defense
      against oxidative stress damage. Herein, we investigated whether autophagy played
      a regulatory role in TCDD-induced neurotoxicity. Here, we showed that TCDD
      exposure caused marked autophagy in SH-SY5Y cells, whose dose range was close to
      that inducing apoptosis. Electron microscopic and Western blot analyses revealed
      that TCDD induced autophagy at a starting dose of approximate 100 nM.
      Interestingly, 100-200 nM TCDD exposure resulted in obviously decreased cell
      viability and evident apoptotic phenotype. Furthermore, the levels of pro
      apoptotic molecules, Bax and cleaved-PARP, increased significantly, whereas Bcl2
      declined after exposed to 100 nM TCDD. In addition, the apoptosis was verified
      using flow cytometrical analysis. These data strongly suggested that TCDD induced
      both autophagy and apoptosis at a similar dose range in SH-SY5Y cells.
      Interestingly, pretreatment with ROS scavenger, N-acetyl-cysteine (NAC), could
      effectively block both TCDD-induced apoptosis and autophagy. More surprisingly,
      inhibition of autophagy with 3-methyladenine (3MA), remarkably augmented TCDD
      induced apoptosis. The findings implicated that the onset of autophagy might
      serve as a protective mechanism to ameliorate ROS-triggered cytotoxic effects in
      human SH-SY5Y neuronal cells under TCDD exposure. (c) 2015 Wiley Periodicals,
      Inc. Environ Toxicol 31: 1068-1079, 2016. 

PMID- 25865074
TI  - A 2H-tetrahydropyran derivative and bioactive constituents from the bark of
      Goniothalamus elegants Ast.
AB  - A new 2H-tetrahydropyran derivative, 6-epi-goniothalesdiol A (1), together with
      nine known styryllactones (2-10) and five known aristolactams (11-15) were
      isolated from the bark of Goniothalamus elegants Ast. The structures were
      elucidated by spectroscopic methods. The isolated compounds were evaluated for
      their cytotoxicity toward the KB, MCF7 and NCI-H187 cell lines as well as
      antimalarial and antimycobacterial activities. Compounds 4 and 10 showed strong
      activity against all three human cancer cell lines with IC50 values in the range
      of 0.538 to 4.25 MUg/ml, while compounds 2, 4, 10 and 14 showed potent
      cytotoxicity against NCI-H187 with IC50 values in the range of 0.072 to 2.17
      MUg/ml. In addition, compounds 4, 6, 7, 9, 10 and 13 showed strong antiplasmodial
      activity with IC50 in the range of 2.28 to 5.89 MUg/ml.

PMID- 25865075
TI  - Hydrothermal synthesis, X-ray structure and DFT and magnetic studies of a
      (H2SiW12O40)(2-) based one-dimensional linear coordination polymer.
AB  - In this paper, we report the synthesis and characterization of a novel hybrid
      with an inorganic-organic structure formulated as
      [[Nd2(L(1))2(L(2))(H2O)7][H2SiW12O40]]n.4H2O (1), in which HL(1) = nicotinic acid
      and H2L(2) = 2-hydroxynicotinic acid. Interestingly, L(1) and L(2) are generated
      from an in situ transformation of the original ligand, pyridine-2,3-dicarboxylic
      acid under hydrothermal conditions. Structural analysis showed that this compound
      is a one-dimensional linear coordination polymer constructed from a repetition of
      the Keggin anion as a bidentate bridging ligand and one propeller-like dinuclear
      neodymium complex. Furthermore, in the packing arrangement, hydrogen bonds and
      anion-pi interactions connect the adjacent chains to extend the structure into a
      3D architecture. The magnetic properties of this compound have also been studied
      by measuring its magnetic susceptibility in the temperature range 1.8-300 K. We
      also analyzed the coordination ability of the SiW12 Keggin anion in the reported
      structures up to now. Finally, we have performed a DFT computational study on the
      noncovalent anion-pi interactions between the Keggin anion and the aromatic
      ligands coordinated to Nd.

PMID- 25865076
TI  - Authoritarian Disbeliefs in Diversity.
AB  - Ethnic diversity poses a threat to authoritarians, as it indicates non-conformism
      to group norms and poses a threat to group conformity. According to authoritarian
      dynamic theory, threats elicit authoritarian reactions in people with
      authoritarian predispositions. In the present article we tested a mediation model
      derived from authoritarian dynamic theory in a sample of 171 students. As
      expected, authoritarian predisposition negatively predicted diversity beliefs.
      This effect was fully mediated by an authoritarian manifestation, that is,
      authoritarian aggression. The two other components of right-wing
      authoritarianism, authoritarian submission and conventionalism, did not mediate
      the effect. Results confirm contemporary research on authoritarianism and the
      differentiation of authoritarian predispositions and its manifestations.

PMID- 25865077
TI  - First experience of liver transplantation with type 2 donation after cardiac
      death in France.
AB  - Organ donation after unexpected cardiac death [type 2 donation after cardiac
      death (DCD)] is currently authorized in France and has been since 2006. Following
      the Spanish experience, a national protocol was established to perform liver
      transplantation (LT) with type 2 DCD donors. After the declaration of death,
      abdominal normothermic oxygenated recirculation was used to perfuse and oxygenate
      the abdominal organs until harvesting and cold storage. Such grafts were proposed
      to consenting patients < 65 years old with liver cancer and without any hepatic
      insufficiency. Between 2010 and 2013, 13 LTs were performed in 3 French centers.
      Six patients had a rapid and uneventful postoperative recovery. However, primary
      nonfunction occurred in 3 patients, with each requiring urgent retransplantation,
      and 4 early allograft dysfunctions were observed. One patient developed a
      nonanastomotic biliary stricture after 3 months, whereas 8 patients showed no
      sign of ischemic cholangiopathy at their 1-year follow-up. In comparison with a
      control group of patients receiving grafts from brain-dead donors (n = 41), donor
      age and cold ischemia time were significantly lower in the type 2 DCD group. Time
      spent on the national organ wait list tended to be shorter in the type 2 DCD
      group: 7.5 months [interquartile range (IQR), 4.0-11.0 months] versus 12.0 months
      (IQR, 6.8-16.7 months; P = 0.08. The 1-year patient survival rates were similar
      (85% in the type 2 DCD group versus 93% in the control group), but the 1-year
      graft survival rate was significantly lower in the type 2 DCD group (69% versus
      93%; P = 0.03). In conclusion, to treat borderline hepatocellular carcinoma, LT
      with type 2 DCD donors is possible as long as strict donor selection is observed.

PMID- 25865078
TI  - Circulating adipocyte fatty acid-binding protein induces insulin resistance in
      mice in vivo.
AB  - OBJECTIVE: Circulating levels of the adipokine adipocyte fatty acid-binding
      protein (AFABP) are increased in obesity. However, the influence of circulating
      AFABP on insulin sensitivity in vivo remains unclear. METHODS: C57BL/6NTac mice
      (10 weeks) were treated over 8 weeks i.p. with saline (control) or recombinant
      AFABP (0.5 mg/kg/d). A comprehensive characterization of metabolic parameters,
      body composition, and energy expenditure was performed. Furthermore, the effect
      of AFABP on pancreatic beta-cell responsiveness, hepatic glycogen content, and
      peroxisome proliferator-activated receptor (PPAR) gamma protein expression was
      elucidated. RESULTS: In male mice, AFABP treatment induced insulin resistance
      with significantly increased fasting insulin, C-peptide, and homeostasis model
      assessment of insulin resistance. In female animals, a similar trend was
      observed. In both genders, no difference in body weight, lipid parameters, body
      composition, or energy expenditure could be detected between AFABP-treated and
      control mice. Insulin resistance in male AFABP-treated mice was accompanied by
      decreased PPARgamma protein content in perigonadal adipose tissue and diminished
      circulating adiponectin. AFABP treatment did not affect pancreatic beta-cell
      responsiveness and hepatic glycogen content. CONCLUSIONS: Circulating AFABP
      induces insulin resistance in male mice. AFABP-mediated degradation of PPARgamma
      in adipose tissue and subsequently decreased expression of insulin-sensitizing
      adiponectin are potential mechanisms for this effect.

PMID- 25865079
TI  - Rh(I)-Catalyzed Hydroamidation of Olefins via Selective Activation of N-H Bonds
      in Aliphatic Amines.
AB  - Hydroamidation of olefins constitutes an ideal, atom-efficient method to prepare
      carboxylic amides from easily available olefins, CO, and amines. So far,
      aliphatic amines are not suitable for these transformations. Here, we present a
      ligand- and additive-free Rh(I) catalyst as solution to this problem. Various
      amides are obtained in good yields and excellent regioselectivities. Notably,
      chemoselective amidation of aliphatic amines takes place in the presence of
      aromatic amines and alcohols. Mechanistic studies reveal the presence of Rh-acyl
      species as crucial intermediates for the selectivity and rate-limiting step in
      the proposed Rh(I)-catalytic cycle. 

PMID- 25865080
TI  - Mineral status of premature infants in early life and linear growth at age 3.
AB  - BACKGROUND: Preterm infants are at significant risk of reduced bone mineral
      content and subsequent bone disease (metabolic bone disease of prematurity,
      MBDP). MBDP is frequently found in very low-birthweight (VLBW) infants, but long
      term height prognosis is not well known. METHODS: VLBW infants from two major
      neonatal intensive care units were studied. Medical records were reviewed. A
      total of 143 subjects were analyzed after excluding subjects who died, or who had
      severe complications that could affect linear growth, Silver-Russell syndrome,
      severe cholestasis, and/or chromosomal abnormality. The relationship between MBDP
      and height at age 3 was investigated. RESULTS: Height standard deviation score
      (SDS) at age 3 negatively correlated with peak serum alkaline phosphatase (ALP)
      activity in early life (r = -0.30, P = 0.0003) and positively correlated with
      serum phosphorus (P) at peak ALP (r = 0.33, P = 0.0002). In addition, serum P
      independently affected height SDS at 3 years of age (beta = 0.19, P = 0.018), and
      was significantly different between infants with and without catch-up growth in
      height (difference: 0.23 mmol/L, 95%CI: 0.09-0.36, P = 0.0010). CONCLUSIONS:
      MBDP, particularly hypophosphatemia in the early period of life, is associated
      with linear growth until 3 years of age in VLBW infants.

PMID- 25865081
TI  - Gastric pull-up reconstruction combined with free jejunal transfer (FJT)
      following total pharyngolaryngo-oesophagectomy (PLE).
AB  - INTRODUCTION: Reconstruction following total pharyngolaryngo-oesophagectomy (PLE)
      still challenges surgeons because of the extreme length of removed tissue.
      Gastric pull-up reconstruction, one of the most common reconstructive methods
      after PLE, has many complications such as anastomotic fistula and gastric
      necrosis caused by the high anastomotic tension. However, modifications of
      gastric pull-up reconstruction aiming to reducing the high anastomotic tension
      have been less reported compared with other aspects with this technique. Here we
      report a modified gastric pull-up reconstruction combined with free jejunal
      transfer (FTJ) to reduce the anastomosis tension, and thus to reduce the risk of
      complications after PLE. METHODS: Patients underwent a standard surgical
      procedure including total pharyngolaryngo-oesophagectomy and bilateral internal
      jugular lymph nodal clearance. A free jejunal graft about 10 cm was harvested and
      placed in the appropriate position between mobilized stomach and oropharynx. The
      anastomosis between the free jejunal graft and the gastric tube was created
      through a stapler. Vascular anastomosis was made between the jejunal artery and
      the transverse cervical artery, and between the jejunal vein and the internal
      jugular vein. Hand suturing technique was used in the anastomosis between jejunum
      and pharynx. RESULTS: None of the patients suffered from any complications such
      as anastomotic fistula. Both patients resumed early postoperative oral intake. So
      far, they remain free of tumor recurrence and are in good health for 46 and 18
      months, respectively. CONCLUSION: Considering the tumor status and the patient
      condition, the gastric pull-up reconstruction combined with FJT after PLE could
      be a reliable choice.

PMID- 25865082
TI  - Does a muscle flap accelerate wound healing of gastric wall defects compared with
      an omental flap?
AB  - INTRODUCTION: Most often used for reconstruction at superficial sites, a muscle
      flap recently was reported to promote clinical wound healing in a duodenal
      defect. We therefore examined whether a muscle flap could promote wound healing
      comparably to an omental flap in rats with gastric wall defects. METHODS: After
      perforation of the centre of the anterior gastric wall, rats were divided into 2
      groups. In the muscle group, a muscle flap was fixed to the defect; in the
      omentum group, an omental flap was placed over the defect. We histopathologically
      compared tissue responses during gastric wall healing. RESULTS: While stratified
      villi had completely covered the defect by day 7 in both groups, scar maturation
      differed. Scar tissue persisted in the muscle group, but was gradually replaced
      by adipose tissue in the omentum group. DISCUSSION: Both muscle and omental flaps
      accelerated gastric wall wound healing. CONCLUSION: A muscle flap is an excellent
      alternative for repair of gastric defects when no omental flap is available.

PMID- 25865083
TI  - Pre-operative unintentional weight loss as a risk factor for surgical outcomes
      after elective surgery in patients with disseminated cancer.
AB  - BACKGROUND: With improvement in survival, elective surgical procedures are being
      increasingly performed on patients with metastatic disease. We aimed to study the
      association of pre-operative unintentional weight loss (UWL) with operative
      outcomes in this patient population. METHODS: We extracted data on all patients
      with disseminated cancer undergoing elective surgeries between 2005 and 2011 from
      the National Surgical Quality Improvement Program (NSQIP), along with the Current
      Procedure Terminology (CPT) codes. Based on the presence of unintentional weight
      loss of >10% body weight in the 6-month period preceding surgery, patients were
      divided into 2 cohorts - (1) patients with UWL ('UWL' cohort) and (2) patients
      without UWL ('No UWL') cohort. Differences in patient characteristics, co-morbid
      conditions and outcomes were compared. RESULTS: There were 30,669 surgeries
      recorded under 1,638 CPT codes, with 8,436 surgeries involving the eight most
      common CPT codes. UWL was present in 11.5% of all patients. UWL patients were
      more commonly (P < 0.05) male, African-American, of higher ASA (American Society
      of Anesthesiology) class, and had multiple associated comorbidities. Nearly all
      complications, including wound infections, prolonged ventilator requirement,
      unplanned intubation, cardiac arrest, DVT, sepsis and mortality were more common
      in UWL patients. Multivariate analysis demonstrated that UWL was independently
      associated with 21%, 22% and 49% higher risk of overall morbidity, serious
      morbidity and 30-day mortality, respectively. CONCLUSION: UWL is an independent
      risk factor associated with increased morbidity and mortality following elective
      surgeries in patients with disseminated cancer.

PMID- 25865084
TI  - Angiographic embolization for major trauma in a low-middle income healthcare
      setting--A retrospective review.
AB  - INTRODUCTION: Interventional radiology (IR) provides a range of adjunctive
      techniques to assist with hemorrhage control after trauma that can be employed
      pre- or post-operatively. The role of IR in lower-middle income countries (LMICs)
      remains unexplored. This study describes the use of adjunctive angioembolization
      (AE) in severely injured patients following its recent implementation at an urban
      trauma center in a LMIC. METHODS: Adult patients (>= 16 years) requiring AE from
      2011 to 2013 at a single trauma-care facility were included. Data was collected
      on demographic parameters, transfer status, injury severity score (ISS),
      emergency resuscitation characteristics, AE and operative characteristics,
      complications, and in-hospital mortality. Descriptive analyses were performed.
      RESULTS: Thirty six patients underwent AE for trauma-related hemorrhagic
      complications and were included in the study. Average age was 31.5 (+/- 11.3)
      years with a male preponderance (91.7%). Penetrating trauma (61.1%) was the most
      common type of injury. The primary mechanism of injury was gunshot (58.3%). The
      median ISS was 24 (IQR: 20-29). Pre-operative AE was performed in 23 (63.9%)
      patients and these patients had a lower median ISS (22) than those who underwent
      post-operative AE (p = 0.015). Hepatic (55.6%) and pelvic (33.3%) trauma more
      commonly required radiological intervention. Bleeding from the right hepatic (n =
      14), and the right internal iliac (n = 6) arteries and/or their branches, were
      more often embolized. Microcoils were the preferred AE agents (61.1%). Median
      length of hospital stay was 7.5 (IQR: 3-14) days. Eight (22.2%) patients did not
      survive. CONCLUSION: With the availability of multi-detector computed tomography
      and a dedicated interventional radiology suite, implementation of AE for the care
      of trauma patients in LMIC settings is possible.

PMID- 25865085
TI  - Is microdialysis useful for early detection of acute rejection after kidney
      transplantation?
AB  - INTRODUCTION: Acute rejection following kidney transplantation (KTx) is still one
      of the challenging complications leading to chronic allograft failure. The aim of
      this study was to investigate the role of microdialysis (MD) in the early
      detection of acute graft rejection factor following KTx in porcine model.
      METHODS: Sixteen pigs were randomized after KTx into case (n = 8, without
      immunosuppressant) and control groups (n = 8, with immunosuppressant). The
      rejection diagnosis in our groups was confirmed by histopathological evidences as
      "acute borderline rejection". Using MD, we monitored the interstitial
      concentrations of glucose, lactate, pyruvate, glutamate and glycerol in the
      transplanted grafts after reperfusion. RESULTS: In the early post-reperfusion
      phase the lactate level in our case group was significantly higher comparing to
      the control group and remained in higher levels until the end of monitoring. The
      lactate to pyruvate ratio showed a considerable increase in the case group during
      the post-reperfusion phase. The other metabolites (glucose, glycerol, glutamate)
      were nearly at the same levels at the end of our monitoring in both study groups.
      CONCLUSION: The increase in lactate and lactate to pyruvate ratios seems to be an
      indicator for early detection of acute rejection after KTx. Therefore, MD as a
      minimally invasive measurement tool may help to identify the need to
      immunosuppression adjustment in the early KTx phase before the clinical
      manifestation of the rejection.

PMID- 25865086
TI  - Fifty top-cited classic papers in orthopedic elbow surgery: A bibliometric
      analysis.
AB  - OBJECTIVE: The number of citations that a paper has received reflects the impact
      of the article within a particular medical area. Citation analysis concerning the
      most cited articles have been widely reported in orthopedic surgery and its
      subspecialties. However, which articles are cited most frequently in orthopedic
      elbow surgery is unknown. This study aimed to identify and analyze the
      characteristics of the 50 most cited articles in elbow surgery. METHODS: Science
      Citation Index Expanded was used to search for citations in 181 journals chosen
      according to the relevance for elbow publications. The 50 most cited articles in
      elbow surgery were identified. The title, authors, year of publications, article
      type, journal source, country, institution, number of citations, decade
      published, citation density and level of evidence were recorded and analyzed.
      RESULTS: The 50 most cited articles were published between 1950 and 2010. The
      1980s was the most productive decade. The number of citations ranged from 388 to
      124. All the articles were written in English and published in nine journals. The
      majority of articles originated from United States, followed by Canada and United
      Kingdom. Fracture was the most discussed topic. The majority of the top cited
      articles were clinical studies, with the remaining basic research. The most
      common level of evidence was level IV. CONCLUSIONS: Identification of the most
      cited papers in elbow surgery shows an insight into the historical development of
      elbow surgery and provides the foundation for further investigations.

PMID- 25865087
TI  - Effectiveness of a multidisciplinary team approach to the prevention of
      readmission for acute glycaemic events.
AB  - AIMS: To describe the effect of a combined diabetes specialist/mental health team
      approach to prevent readmissions for acute glycaemic events among patients with
      diabetes. METHODS: Consecutive patients with diabetes, readmitted to a single
      hospital for an acute glycaemic condition, were offered one or more diabetes
      (including assessment, education, medication, technology use and intensive
      support) and mental health (including assessment, training and therapies)
      interventions. The pilot service took place over 11 months, with the preceding 24
      months and subsequent 8 months serving as control periods. RESULTS: Of the 58
      patients admitted, 50 had Type 1 diabetes and were from within the hospital
      catchment area, and were discharged home. Of these, 32 (64%) had a pre-existing
      mental health issue and 14 (28%) had a complex social situation. In all, 96% of
      patients were met as an inpatient by a team member, and 94% accepted at least one
      intervention. The mean +/-sd number of admissions per patient/month dropped from
      0.12 +/- 0.10 to 0.05 +/- 0.10 (P < 0.001) during the intervention, increasing,
      once the intervention ended, to 0.16 +/- 0.36 (P = 0.002). The mean +/- sd length
      of stay similarly decreased and increased (0.6 +/- 0.9 to 0.2 +/- 0.7 days; P <
      0.001 to 0.006) to 0.6 +/- 1.4 days (P = 0.003) per patient/month) across the
      three periods, as did the mean +/-sd tariff paid per patient/month (?258.0 +/-
      374.0 vs ?92.1 +/- 245.0 vs ?287.3 +/- 563.8; P < 0.001 and P = 0.018,
      respectively). The mean +/- sd HbA1c level dropped from 99 +/- 22 to 92 +/- 24
      mmol/mol (11.2 +/- 4.2% vs 10.6 +/- 4.3%; P = 0.014) but did not increase after
      the intervention [89 +/- 26 mmol/mol (10.4 +/- 4.5%)]. CONCLUSIONS: The cost and
      long-term risks of hospitalization among patients with Type 1 diabetes and
      recurrent admissions can be reduced by a combined specialist diabetes/mental
      health team approach.

PMID- 25865089
TI  - Predictors of extended length of stay after elective shoulder arthroplasty.
AB  - BACKGROUND: With policymakers and hospitals increasingly looking to cut costs,
      length of stay after surgery has come into focus as an area for improvement.
      Despite the increasing popularity of total shoulder arthroplasty, there is
      limited research about the factors contributing to prolonged hospital stay. We
      sought to identify preoperative and postoperative predictors of prolonged
      hospital stay in patients undergoing anatomic total shoulder arthroplasty (ATSA)
      and reverse total shoulder arthroplasty (RTSA). METHODS: Using the 2011
      Nationwide Inpatient Sample, we identified an estimated 40,869 patients who
      underwent elective total shoulder arthroplasty (62.5% ATSA; 37.5% RTSA) and
      separated them into those with normal length of stay (<75th percentile) and
      prolonged length of stay (>75th percentile). Multivariate logistic regression
      modeling was performed to identify factors associated with prolonged length of
      stay. RESULTS: Patient-level factors associated with prolonged length of stay
      common to patients undergoing ATSA or RTSA included increasing age, female sex,
      congestive heart failure, renal failure, chronic pulmonary disease, and
      preoperative anemia. Provider-related factors were lower volume and location in
      the South or Northeast. Postoperative complications showed a significant
      influence as well. CONCLUSION: Our data can be used to promptly identify patients
      at higher risk of prolonged hospitalization after elective shoulder arthroplasty
      and to ultimately improve quality of care and cost containment.

PMID- 25865088
TI  - Shoulder impingement in the United States military.
AB  - BACKGROUND: Little is known about the incidence and characteristics of primary,
      or external, shoulder impingement in an occupationally and physically active
      population. A longitudinal, prospective epidemiologic database was used to
      determine the incidence and risk factors for shoulder subacromial impingement in
      the United States (U.S.) military. Our hypothesis was that shoulder impingement
      is influenced by age, sex, race, military rank, and branch of service. METHODS:
      The Defense Medical Epidemiology Database was queried for all shoulder
      impingement injuries using International Classification of Disease, Ninth
      Addition, Clinical Modification code 726.10 within a 10-year period from 1999
      through 2008. An overall injury incidence was calculated, and a multivariate
      analysis performed among demographic groups. RESULTS: In an at-risk population of
      13,768,534 person-years, we identified 106,940 cases of shoulder impingement
      resulting in an incidence of 7.77/1000 person-years in the U.S. military. The
      incidence of shoulder impingement increased with age and was highest in the group
      aged >=40 years (incidence rate ratio [IRR], 4.90; 95% confidence interval [CI],
      4.61-5.21), was 9.5% higher among men (IRR, 1.10, 95% CI, 1.06-1.13), and
      compared with service members in the Navy, those in the Air Force, Army, and
      Marine Corps were associated with higher rates of shoulder impingement (IRR, 1.46
      [95% CI, 1.42-1.50], 1.42 [95% CI, 1.39-1.46], and 1.31 [95% CI, 1.26-1.36],
      respectively). CONCLUSIONS: The incidence of shoulder impingement among U.S.
      military personnel is 7.77/1000 person-years. An age of >=40 years was a
      significant independent risk factor for injury.

PMID- 25865090
TI  - Biological responses to flexion/extension in spinal segments ex-vivo.
AB  - Mechanical loading is a salient factor in the progression of spinal disorders
      that contribute to back pain. Biological responses to loading modes like
      flexion/extension (F/E) in relevant spinal tissues remain unstudied. A novel,
      multi-axial experimental system was developed to subject viable functional spinal
      units (FSUs) to complex, in-situ loading. The objective was to determine
      biological effects of F/E in multiple spinal tissues-annulus fibrosus, nucleus
      pulposus, facet cartilage, and ligamentum flavum. Rabbit lumbar FSUs were mounted
      in a bioreactor within a robotic testing system. FSUs underwent small (0.17/0.05
      Nm) and large (0.5/0.15 Nm) range-of-motion F/E for 1 or 2 h of cycling. Outcomes
      in each tissue, compared to unloaded FSUs, included (i) relative mRNA expression
      of catabolic (MMP-1, 3 and ADAMTS-5), pro-inflammatory (COX-2), and anabolic
      (ACAN) genes and (ii) immunoblotting of aggrecan degradation. Total energy
      applied to FSUs increased in groups subject to large range-of-motion and 2-h
      cycling, and moment relaxation was higher with large range-of-motion. F/E
      significantly modulated MMP1,-3 and COX-2 in facet cartilage and MMP-3 and ACAN
      in annulus fibrosus. Large range-of-motion loading increased MMP-mediated
      aggrecan fragmentation in annulus fibrosus. Biological responses to complex
      loading ex vivo showed variation among spinal tissues that reflect tissue
      structure and mechanical loading in F/E.

PMID- 25865092
TI  - Improved Zernike-type phase contrast for transmission electron microscopy.
AB  - Zernike phase contrast has been recognized as a means of recording high
      resolution images with high contrast using a transmission electron microscope.
      This imaging mode can be used to image typical phase objects such as unstained
      biological molecules or cryosections of biological tissue. According to the
      original proposal discussed in Danev and Nagayama (2001) and references therein,
      the Zernike phase plate applies a phase shift of pi/2 to all scattered electron
      beams outside a given scattering angle and an image is recorded at Gaussian focus
      or slight underfocus (below Scherzer defocus). Alternatively, a phase shift of 
      pi/2 is applied to the central beam using the Boersch phase plate. The resulting
      image will have an almost perfect contrast transfer function (close to 1) from a
      given lowest spatial frequency up to a maximum resolution determined by the wave
      length, the amount of defocus and the spherical aberration of the microscope. In
      this paper, I present theory and simulations showing that this maximum spatial
      frequency can be increased considerably without loss of contrast by using a
      Zernike or Boersch phase plate that leads to a phase shift between scattered and
      unscattered electrons of only pi /4, and recording images at Scherzer defocus.
      The maximum resolution can be improved even more by imaging at extended Scherzer
      defocus, though at the cost of contrast loss at lower spatial frequencies. 

PMID- 25865091
TI  - Examining associations between negative urgency and key components of objective
      binge episodes.
AB  - OBJECTIVE: Negative urgency (NU; tendency to act impulsively when experiencing
      negative emotions) is a risk factor for binge eating, although few studies have
      examined interviewer-assessed objective binge episodes (OBEs). Moreover, research
      has not investigated how NU relates to the core components of OBEs: loss of
      control (LOC) eating and objective overeating (OO). Understanding the
      relationship between NU and these core components will enhance etiologic models
      of eating disorder development. Thus, the current study examined the associations
      between NU, OBEs, and the components of OBEs by comparing levels of NU in women
      with OBEs, LOC eating only, and OO only to women with no pathological eating.
      METHOD: Participants were 612 women who endorsed lifetime OBEs (5.4%), LOC eating
      outside of OBEs (5.7%), OO only (2.8%), or none of these eating episodes (85.9%).
      RESULTS: Women with OBEs, LOC only, and OO only had significantly higher levels
      of NU than women without these episodes, suggesting that NU is associated with
      both the LOC and OO components of OBEs. DISCUSSION: NU relates to the spectrum of
      pathology present in women with OBEs. Future research should examine the
      mechanisms underlying these associations, including impaired
      behavioral/psychological control and/or increased reward sensitivity in response
      to negative affect.

PMID- 25865093
TI  - Patient Perspectives of Acute Pain Management in the Era of the Opioid Epidemic.
AB  - STUDY OBJECTIVE: To inform the development of interventions that could improve
      patient engagement around the risks and benefits of alternative approaches to
      pain management in the emergency department (ED), we seek to capture the
      perspectives and experiences of patients treated for pain in this setting.
      METHODS: Three trained interviewers conducted semistructured open-ended telephone
      interviews with patients discharged from a single urban academic ED after
      presenting with acute pain related to fracture, renal colic, or musculoskeletal
      back injury. We recruited subjects until achieving thematic saturation according
      to periodic review of the interview transcripts. Interviews were audio recorded,
      professionally transcribed, and uploaded into QSR NVivo (version 10.0) for coding
      and analysis using modified grounded theory. An interdisciplinary team double
      coded the data and convened to review emerging themes, ensure interrater
      reliability, and establish consensus on discrepancies. RESULTS: We had 23
      completed subject interviews, the majority of which were women. Interrater
      reliability for coding exceeded 90%. The major themes elicited centered on
      domains of patient awareness of the potential for opioid dependence and patient
      provider communication relating to pain management. From the patient perspective,
      emergency physicians typically do not present alternative pain management options
      or discuss the risks of opioid dependence. Patients with negative experiences
      related to pain management describe deficiencies in patient-provider
      communication leading to misunderstanding of clinical diagnoses, fragmentation of
      care among their health care providers, and a desire to be involved in the
      decisionmaking process around their pain management. Patients with positive
      experiences commented on regular communication with their care team, rapid pain
      management, and the empathetic nature of their care providers. Patients
      communicate fears about the risks of opioid addiction, beliefs that following a
      prescribed opioid regimen is protective of developing opioid dependence, and an
      understanding of the broader tensions that providers face relating to the
      prescription of opioid therapy. CONCLUSION: Patients identified a deficit of
      communication around opioid risk and pain management options in the ED.

PMID- 25865095
TI  - The prevalence of attention-deficit/hyperactivity disorder among school-aged
      children in Benin City, Nigeria.
AB  - OBJECTIVE: To establish the prevalence of ADHD among school-aged children in
      Benin City, Nigeria. METHOD: A total of one thousand, three hundred and eighty
      four (1384) primary school pupils, aged between six and 13 years, were recruited
      from six primary schools. Teacher's ratings of the 18 DSM-IV symptoms of ADHD
      were collected and analysed as a function of gender and subtype. RESULTS: The
      results support a documented trend in ADHD reports: males had a higher prevalence
      rate. The prevalence rate of 8.0% found is also consistent with documented
      evidence. Conclusion The results strengthen earlier observations that there is no
      significant geographical variation on the prevalence of ADHD if common
      definitions and diagnostic tools are employed. This study being the first from
      Nigeria provides data for crosscultural comparison as a prerequisite for
      establishing a common knowledge of ADHD.

PMID- 25865096
TI  - Family predictors of adolescent substance use: the case of high school students
      in the Cape Metropolitan Area, Cape Town, South Africa.
AB  - Family predictors of tobacco and alcohol use were studied in random samples of
      school-going Black, Coloured, and White adolescents (total N=1,800) in the Cape
      Town Metropolitan Area. The subjects ranged in age from 14 to 17 years, with a
      mean age of 15.95 years. Logistic regression analysis of the data showed
      invariance across the three racial groups in terms of the specific family
      variables that were predictive, as well as their direction and magnitude of
      association with substance use. Essentially, higher rates of substance use for
      all three groups were predicted by parental behavioural control, parental
      monitoring/knowledge and limit setting, marital relations and family stress. The
      findings extend the work on South African adolescent substance use by providing a
      view into the proximal (family) socialising forces that are related to substance
      use. The findings also extend the broader work on identifying specialised effects
      of dimensions of socialization on adolescent functioning. The discussion section
      includes commentary on the cultural invariance found when measuring socialising
      forces at this level of generality. 

PMID- 25865094
TI  - Optimum treatment strategies for carbapenem-resistant Acinetobacter baumannii
      bacteremia.
AB  - Carbapenem-resistant Acinetobacter baumannii (CRAB) constitutes an increasing
      problem worldwide. CRAB bacteremia is associated with a high fatality rate and
      its optimal treatment has not been established. Early institution of appropriate
      therapy is shown to improve survival of patients with CRAB bloodstream infection.
      Regrettably, treatment options are limited. Little information exists about the
      efficacy of sulbactam for the treatment of CRAB bacteremia. Colistin and
      tigecycline possess good in vitro activity and represent in many cases the only
      therapeutic options although clinical data are scarce. The need for a loading
      dose of colistin has been recently demonstrated to rapidly achieve therapeutic
      levels. The use of combination therapy is also a matter of debate but current
      evidence do not support its routine use. 

PMID- 25865097
TI  - Criminal capacity in children accused of murder: challenges in the forensic
      mental health assessment.
AB  - Around the world there appears to have been an increase in child-perpetrated
      crimes, with South Africa being no exception. Of particular concern is the
      involvement of children in the perpetration of violent crimes, such as murder.
      This phenomenon is resulting in greater focus on the role of psychiatric and
      psychological testimony in the trials of accused youths. While mental health
      professionals have long been involved in the forensic assessment of adults, their
      role in the assessment of child accused is less well documented. As a result
      there is still a great deal of development and refinement needed in this area, in
      order that the task can be executed with more clarity and precision. Currently,
      South African law contains the presumption that a child under the age of seven
      years is doli incapax (i.e. he or she cannot be held criminally responsible),
      while there is a rebuttable doli incapax presumption in the case of children
      between the ages of seven and 14 years. The age of the accused, together with
      developmental and social competence indices, are crucial variables that influence
      the acceptance or rebuttal of the doli incapax presumption. The paper discusses
      the challenges in the forensic mental health assessment of children accused of
      murder. 

PMID- 25865098
TI  - The management of traumatic stress disorder in infants.
AB  - The number of very young children exposed to trauma is under-represented. Trauma
      interferes with the organisation and development of brain structures and thus may
      have lasting effects on the individual's life. Traumatic stress disorder (TSD),
      which is the Axis I diagnosis used in the under-three patient population,
      encompasses four symptom clusters. Of note is the integral part of the
      Relationship Disorder Classification (Axis II) during this phase of life. The
      capacities needed to experience and recall early trauma are largely present from
      the beginning of life and rapidly develop during the first six months. The
      treatment of traumatic stress disorder rests on establishing a sense of safety,
      reducing the overwhelming affects evoked, helping the child to form a coherent
      narrative and thereby aiding the integration and psychological mastery of the
      traumatic event. The support of the attachment relationship with an adequate
      caregiver is pivotal. 

PMID- 25865100
TI  - Working with Groups by Lily Becker (ed.).

PMID- 25865099
TI  - Cognitive behavioral therapy for adolescent depression: implications for Asian
      immigrants in the United States of America.
AB  - Many interventions are available for treating adolescent depression. This paper
      attempts to present a summary of cognitive behavioral therapies/techniques that
      might be useful for treating depression in Asian immigrant adolescents. Articles
      were selected by conducting a literature search on Psyc-Info. Prevalence,
      symptoms and measures of adolescent depression are discussed. Summary of popular
      therapies like PASCET, CWD-A, Beck's CBT are provided. A rationale for the use of
      these with Asian immigrants is hypothesized. There is no empirical evidence for
      the efficacy of CBT with this population. A need to validate the use of CBT with
      this population is asserted. 

PMID- 25865101
TI  - Youth: choices and change. Promoting healthy behaviors in adolescents by cecelia
      breinbauer and matilde maddeleno.

PMID- 25865103
TI  - Journal abstracts from current research in the field of child and adolescent
      mental health.

PMID- 25865102
TI  - Your angry child: a guide for parents by daniel L davis.

PMID- 25865104
TI  - Adolescent sexuality: beyond controversy.

PMID- 25865105
TI  - South African children: future social capital vs failure and despair.

PMID- 25865106
TI  - Unprecedented one-pot synthesis of an unsymmetrical cisplatin-based Pt(IV)
      acetamidato complex.
AB  - We describe herein a novel Pt(IV)-acetamidato complex as a result of the one-pot
      reaction between cisplatin and the highly reactive peroxyacetimidic acid
      generated in situ. This is the first example of a Pt(IV) complex containing a N
      donor ligand coordinated during the Pt(II) -> Pt(IV) oxidation step. Remarkably,
      the Pt(IV)-amidato compound is highly soluble and stable in water; it represents
      an interesting building block for the further development of Pt(IV) antitumor
      prodrugs.

PMID- 25865108
TI  - Metronidazole-induced encephalopathy with contrast enhancing lesions on MRI.

PMID- 25865109
TI  - TRIP: a pathological score for transarterial chemoembolization resistance
      individualized prediction in hepatocellular carcinoma.
AB  - BACKGROUND & AIMS: Although potentially very useful in optimizing patient
      selection and follow-up, the individual response to transarterial
      chemoembolization (TACE) in hepatocellular carcinoma (HCC) is generally
      unpredictable. The aim of this study was to identify tissue predictors of tumour
      resistance to TACE for use in clinical practice on pretreatment biopsies.
      METHODS: We investigated the association of residual tumour in post-TACE-resected
      HCC with pathological and immunophenotypical features, mainly related to hypoxia
      and angiogenesis. Comparison of tumour phenotype between post-TACE HCC and both
      paired pre-TACE biopsies and control TACE-untreated HCC was performed. Cases
      showing >50% residual tumour (RT) were defined as TACE-resistant. RESULTS: A
      consecutive series of 108 HCC from 41 patients was studied. Overall, 45/108 (44%)
      HCC were classified as TACE-resistant. Among these, 32 (71%) and 40 (89%) showed
      diffuse CD34 vascular staining and negative VEGF staining respectively (p<0.05).
      The association of these two parameters in a weighted score (TRIP) was able to
      predict TACE resistance with 81% accuracy, 89% sensitivity and 59% specificity.
      The effectiveness of TRIP was validated in an independent series of 28 HCC
      biopsies from patients subsequently treated with TACE and for whom radiological
      follow-up was available. CONCLUSIONS: This study demonstrates the potential value
      of pretreatment tumour biopsy as predictors of TACE resistance in HCC.

PMID- 25865110
TI  - The old transplant recipient that becomes a liver donor.

PMID- 25865107
TI  - Gene therapy to restore electrophysiological function in heart failure.
AB  - INTRODUCTION: Heart failure (HF) is a major public health epidemic and a leading
      cause of morbidity and mortality in the industrialized world. Existing treatments
      for patients with HF are often associated with pro-arrhythmic activity and risk
      of sudden cardiac death. Therefore, development of novel, effective and safe
      therapeutic options for HF patients is a critical area of unmet need. AREAS
      COVERED: In this article, we review recent advances in the emerging field of
      cardiac gene therapy for the treatment of tachy- and bradyarrhythmias in HF. We
      provide an overview of gene-based approaches that modulate myocardial conduction,
      repolarization, calcium cycling and adrenergic signaling to restore heart rate
      and rhythm. EXPERT OPINION: We highlight major advantages of gene therapy for
      arrhythmias, including the ability to selectively target specific cell
      populations and to limit the therapeutic effect to the region that requires
      modification. We illustrate how advances in our fundamental understanding of the
      molecular origins of arrhythmogenic disorders are allowing investigators to use
      targeted gene-based approaches to successfully correct abnormal excitability in
      the atria, ventricles and conduction system. Translation of various gene therapy
      approaches to humans may revolutionize our ability to combat lethal arrhythmias
      in HF patients.

PMID- 25865111
TI  - Neutrophil-lymphocyte and platelet-lymphocyte ratio in patients after resection
      for hepato-pancreatico-biliary malignancies.
AB  - BACKGROUND AND OBJECTIVES: We sought to determine whether Neutrophil-lymphocyte
      ratio (NLR) or platelet-lymphocyte ratio (PLR) were associated with outcomes of
      patients undergoing surgery for a hepatopancreatico-biliary (HPB) malignancy.
      METHOD: Between 2000 and 2013, 452 patients who underwent an HPB procedure for a
      malignant indication were identified. Clinicopathological characteristics, NLR,
      and PLR, as well as short- and long-term outcomes were analyzed. High NLR and PLR
      were classified using a cut-off value of 5 and 190, respectively, based on ROC
      curve analysis. RESULTS: Patients with low versus high NLR and PLR had similar
      baseline characteristics with regard to performance status and tumor stage (all P
      > 0.05). Elevated PLR (HR = 1.40) tends to be association with shorter recurrence
      free survival (RFS) (P = 0.05), whereas NLR was not a predictor of shorter RFS.
      Differently, both elevated NLR (HR = 1.94) and PLR (HR = 1.79) were associated
      with worse overall survival (OS) (both P < 0.05). Patients with NLR >=5 and those
      with PLR >=190 had a significantly shorter OS compared to patients with NLR <5
      and PLR <190, respectively (log-rank test, both P < 0.05). Moreover, patients who
      had both NLR and PLR elevated had worse OS compared to patients with either one
      or none inflammatory markers elevated (log-rank P = 0.02). CONCLUSION: Elevated
      NLR and PLR were predictors of worse long-term outcome among patients with HPB
      malignancy undergoing resection.

PMID- 25865112
TI  - Both intravenous and subcutanous infusion can be done in nursing homes.

PMID- 25865113
TI  - Size effects of single-walled carbon nanotubes on in vivo and in vitro pulmonary
      toxicity.
AB  - To elucidate the effect of size on the pulmonary toxicity of single-wall carbon
      nanotubes (SWCNTs), we prepared two types of dispersed SWCNTs, namely relatively
      thin bundles with short linear shapes (CNT-1) and thick bundles with long linear
      shapes (CNT-2), and conducted rat intratracheal instillation tests and in vitro
      cell-based assays using NR8383 rat alveolar macrophages. Total protein levels,
      MIP-1alpha expression, cell counts in BALF, and histopathological examinations
      revealed that CNT-1 caused pulmonary inflammation and slower recovery and that
      CNT-2 elicited acute lung inflammation shortly after their instillation.
      Comprehensive gene expression analysis confirmed that CNT-1-induced genes were
      strongly associated with inflammatory responses, cell proliferation, and immune
      system processes at 7 or 30 d post-instillation. Numerous genes were
      significantly upregulated or downregulated by CNT-2 at 1 d post-instillation. In
      vitro assays demonstrated that CNT-1 and CNT-2 SWCNTs were phagocytized by NR8383
      cells. CNT-2 treatment induced cell growth inhibition, reactive oxygen species
      production, MIP-1alpha expression, and several genes involved in response to
      stimulus, whereas CNT-1 treatment did not exert a significant impact in these
      regards. These results suggest that SWCNTs formed as relatively thin bundles with
      short linear shapes elicited delayed pulmonary inflammation with slower recovery.
      In contrast, SWCNTs with a relatively thick bundle and long linear shapes
      sensitively induced cellular responses in alveolar macrophages and elicited acute
      lung inflammation shortly after inhalation. We conclude that the pulmonary
      toxicity of SWCNTs is closely associated with the size of the bundles. These
      physical parameters are useful for risk assessment and management of SWCNTs.

PMID- 25865114
TI  - Cystic Angiomyolipoma Mimicking Cystic Renal Cell Carcinoma on Computed
      Tomography Image.
AB  - We report on a 44-year-old male patient with cystic angiomyolipoma (AML)
      simulating cystic renal cell carcinoma on computed tomography (CT). The CT scan
      showed a 2.8-cm left renal cystic mass with an enhancing solid component. No fat
      density was identified in the mass. These findings were indicative of a cystic
      renal cell carcinoma. Robot-assisted laparoscopic partial nephrectomy was
      performed, but the final histologic result was a cystic AML. Herein, we would
      review the preoperative CT findings, which could have suggested cystic AML. 

PMID- 25865115
TI  - The Investigation of Relationship between Coronary Artery Ectasia, Benign
      Prostatic Enlargement, and Lower Urinary Tract Symptoms.
AB  - OBJECTIVE: To investigate benign prostatic enlargement (BPE) and lower urinary
      tract symptoms (LUTS) in patients with coronary artery ectasia (CAE). The
      relation between CAE, BPE, and LUTS has not been studied so far. METHODS: We
      investigated BPE and LUTS symptoms in 47 men with CAE, 45 men with coronary
      artery disease (CAD), and 47 male controls with normal coronary arteries. LUTS
      was evaluated by the International Prostate Symptom Score (IPSS). BPE was
      evaluated with transabdominal ultrasonography. CAD was defined as myocardial
      infarction and angiographically diagnosed coronary disease. CAE was defined as
      being without any stenotic lesions with a visual assessment of the coronary
      arteries showing a luminal dilatation >=1.5 fold of the adjacent normal coronary
      segments. RESULTS: Prostate volume was higher in CAE and CAD patients compared
      with that of the control subjects, respectively (41.0 +/- 10.4 vs 33.5 +/- 9.4
      cm(3); 39.1 +/- 10.3 vs 33.5 +/- 9.4 cm(3); P = .0001); total IPSS was higher in
      CAD and CAE patients compared with that of the control subjects (P = .0001).
      Postmictional residual urine volume was higher in CAE and CAD patients compared
      with that of the control subjects (P = .002). CONCLUSION: We showed that patients
      with CAE have higher prostate volume, IPSS, and postmictional residual urine
      volume compared with those of controls with normal coronary angiograms. This
      study proposes that BPE, LUTS, and CAE maybe different disorders to a common
      vascular pathology and endothelial dysfunction. This study showed that BPE and
      LUTS were frequently seen in CAE at least as much as in CAD. Therefore, LUTS and
      BPE should be kept in mind for CAE patients in follow-ups.

PMID- 25865116
TI  - Cross-regulation between cytokine and microRNA pathways in T cells.
AB  - microRNA (miRNA) mediated regulation of protein expression has emerged as an
      important mechanism in T-cell physiology, from development and survival to
      activation, proliferation, and differentiation. One of the major classes of
      proteins involved in these processes are cytokines, which are both key input
      signals and major products of T-cell function. Here, we summarize the current
      data on the molecular cross-talk between cytokines and miRNAs: how cytokines
      regulate miRNA expression, and how specific miRNAs control cytokine production in
      T cells. We also describe the inflammatory consequences of deregulating the
      miRNA/cytokine axis in mice and humans. We believe this topical area will have
      key implications for immune modulation and treatment of autoimmune pathology. 

PMID- 25865117
TI  - In vitro and in vivo human metabolism of the synthetic cannabinoid AB-CHMINACA.
AB  - N-[(1S)-1-(aminocarbonyl)-2-methylpropyl]-1-(cyclohexylmethyl)-1H-indazole-3
      carboxamide (AB-CHMINACA) is a recently introduced synthetic cannabinoid. At
      present, no information is available about in vitro or in vivo human metabolism
      of AB-CHMINACA. Therefore, biomonitoring studies to screen AB-CHMINACA
      consumption lack any information about the potential biomarkers (e.g.
      metabolites) to target. To bridge this gap, we investigated the in vitro
      metabolism of AB-CHMINACA using human liver microsomes (HLMs). Formation of AB
      CHMINACA metabolites was monitored using liquid chromatography coupled to time-of
      flight mass spectrometry. Twenty-six metabolites of AB-CHMINACA were detected
      including seven mono-hydroxylated and six di-hydroxylated metabolites and a
      metabolite resulting from N-dealkylation of AB-CHMINACA, all produced by
      cytochrome P450 (CYP) enzymes. Two carboxylated metabolites, likely produced by
      amidase enzymes, and five glucuronidated metabolites were also formed. Five mono
      hydroxylated and one carboxylated metabolite were likely the major metabolites
      detected. The involvement of individual CYPs in the formation of AB-CHMINACA
      metabolites was tested using a panel of seven human recombinant CYPs (rCYPs). All
      the hydroxylated AB-CHMINACA metabolites produced by HLMs were also produced by
      the rCYPs tested, among which rCYP3A4 was the most active enzyme. Most of the in
      vitro metabolites of AB-CHMINACA were also present in urine obtained from an AB
      CHMINACA user, therefore showing the reliability of the results obtained using
      the in vitro metabolism experiments conducted to predict AB-CHMINACA in vivo
      metabolism. The AB-CHMINACA metabolites to target in biomonitoring studies using
      urine samples are now reliably identified and can be used for routine analysis.

PMID- 25865118
TI  - Contemporary management of prosthetic valve endocarditis: principals and future
      outlook.
AB  - Infective endocarditis involving prosthetic valves accounts for 20% of all
      endocarditis cases. Rising in prevalence due to increasing placement of valvular
      prostheses, prosthetic valve endocarditis (PVE) is more difficult to diagnose by
      conventional methods, associated with more invasive infection and increased
      mortality. This report explores the existing literature in identifying a direct
      approach to the management of PVE; such as adjuncts to establishing a diagnosis
      (for instance positron emission tomography/computed tomography and radiolabeled
      leukocyte scintigraphy), the trends in specific pathogens associated with PVE and
      the recommended antimicrobials for each. The patterns of disease requiring
      surgical intervention are also highlighted and explored. In addition, a 5-year
      outlook offers consolidated knowledge on epidemiological trends of both culprit
      organisms and population subgroups suffering (and projected to suffer) from PVE. 

PMID- 25865119
TI  - Decoding the regulatory landscape of melanoma reveals TEADS as regulators of the
      invasive cell state.
AB  - Transcriptional reprogramming of proliferative melanoma cells into a
      phenotypically distinct invasive cell subpopulation is a critical event at the
      origin of metastatic spreading. Here we generate transcriptome, open chromatin
      and histone modification maps of melanoma cultures; and integrate this data with
      existing transcriptome and DNA methylation profiles from tumour biopsies to gain
      insight into the mechanisms underlying this key reprogramming event. This shows
      thousands of genomic regulatory regions underlying the proliferative and invasive
      states, identifying SOX10/MITF and AP-1/TEAD as regulators, respectively.
      Knockdown of TEADs shows a previously unrecognized role in the invasive gene
      network and establishes a causative link between these transcription factors,
      cell invasion and sensitivity to MAPK inhibitors. Using regulatory landscapes and
      in silico analysis, we show that transcriptional reprogramming underlies the
      distinct cellular states present in melanoma. Furthermore, it reveals an
      essential role for the TEADs, linking it to clinically relevant mechanisms such
      as invasion and resistance. 

PMID- 25865121
TI  - Real Time Three-Dimensional Echocardiographic Evaluations of Fetal Left
      Ventricular Stroke Volume, Mass, and Myocardial Strain: In Vitro and In Vivo
      Experimental Study.
AB  - BACKGROUND: Left ventricular stroke volume, mass, and myocardial strain are
      valuable indicators of fetal heart function. This study investigated the
      feasibility of nongated real time three-dimensional echocardiography (RT3DE) to
      determine fetal stroke volume (SV), left ventricular mass (LVM), and myocardial
      strain under different conditions. METHODS: To evaluate fetal hearts, fetal-sized
      rabbit hearts were used in this study. The in vitro portion of this study was
      carried out using a balloon inserted into the LV of eight fresh rabbit hearts and
      driven by a calibrated pulsatile pump. RT3DE volumes were obtained at various
      pump-set SVs. The in vivo experiments in this study were performed on open-chest
      rabbits. RT3DE volumes were acquired at the following conditions: baseline,
      simulated hypervolemia, inferior vena cava (IVC) ligation, and ascending aorta
      (AAO) ligation. Displacement values and sonomicrometry data were used as
      references for RT3DE-derived SV, LVM, longitudinal strain (LS), and
      circumferential strain (CS). RESULTS: Excellent correlations between RT3DE
      derived values and reference values were demonstrated and accompanied by high
      coefficients of determination (R(2) ) for both in vitro and in vivo studies for
      SV, LVM, LS, and CS (in vitro: SV: R(2)  = 0.98; LVM: R(2)  = 0.97; LS: R(2)  =
      0.87, CS: R(2)  = 0.80; in vivo: SV: R(2)  = 0.92; LVM: R(2)  = 0.98; LS: in
      vivo: R(2)  = 0.84; CS: in vivo: R(2)  = 0.76; all P < 0.05). CONCLUSIONS: RT3DE
      is capable of quantifying the SV, LVM, and myocardial strain of fetal-sized
      hearts under different conditions. This nongated RT3DE may aid the evaluation of
      fetal cardiac function, providing a superior understanding of the progress of
      fetal heart disorders.

PMID- 25865120
TI  - Borderline personality disorder in transition age youth with bipolar disorder.
AB  - OBJECTIVE: To determine the longitudinal impact of borderline personality
      disorder (BPD) on the course and outcome of bipolar disorder (BP) in a pediatric
      BP sample. METHOD: Participants (N = 271) and parents from the Course and Outcome
      of Bipolar Youth (COBY) study were administered structured clinical interviews
      and self-reports on average every 8.7 months over a mean of 93 months starting at
      age 13.0 +/- 3.1 years. The structured interview for DSM-IV personality disorders
      (SIDP-IV) was administered at the first follow-up after age 18 to assess for
      symptoms of BPD. BPD operationalized at the disorder, factor, and symptom level,
      was examined as a predictor of poor clinical course of BP using all years of
      follow-up data. RESULTS: The number of BPD symptoms was significantly associated
      with poor clinical course of BP, above and beyond BP characteristics. Affective
      dysregulation was most strongly associated with poor course at the factor level;
      the individual symptoms most strongly associated with poor course were
      dissociation/stress-related paranoid ideation, impulsivity, and affective
      instability. CONCLUSION: BPD severity adds significantly to the burden of BP
      illness and is significantly associated with a more chronic and severe course and
      outcome beyond what can be attributable to BP characteristics.

PMID- 25865122
TI  - Medical tourism's impacts on health worker migration in the Caribbean: five
      examples and their implications for global justice.
AB  - Medical tourism is a practice where individuals cross international borders in
      order to access medical care. This practice can impact the global distribution of
      health workers by potentially reducing the emigration of health workers from
      destination countries for medical tourists and affecting the internal
      distribution of these workers. Little has been said, however, about the impacts
      of medical tourism on the immigration of health workers to medical tourism
      destinations. We discuss five patterns of medical tourism-driven health worker
      migration to medical tourism destinations: 1) long-term international migration;
      2) long-term diasporic migration; 3) long-term migration and 'black sheep'; 4)
      short-term migration via time share; and 5) short-term migration via patient
      provider dyad. These patterns of health worker migration have repercussions for
      global justice that include potential negative impacts on the following: 1)
      health worker training; 2) health worker distributions; 3) local provision of
      care; and 4) local economies. In order to address these potential negative
      impacts, policy makers in destination countries should work to ensure that
      changes in health worker training and licensure aimed at promoting the medical
      tourism sector are also supportive of the health needs of the domestic
      population. Policy makers in both source and destination countries should be
      aware of the effects of medical tourism on health worker flows both into and out
      of medical tourism destinations and work to ensure that the potential harms of
      these worker flows to both groups are mitigated. 

PMID- 25865123
TI  - Characterization of phenotype variations of luminescent and non-luminescent
      variants of Vibrio harveyi wild type and quorum sensing mutants.
AB  - Vibrio harveyi, a luminescent Gram-negative motile marine bacterium, is an
      important pathogen responsible for causing severe diseases in shrimp, finfish and
      molluscs leading to severe economic losses. Non-luminescent V. harveyi obtained
      by culturing luminescent strains under static and dark condition were reported to
      alter the levels of virulence factors and metalloprotease gene and luxR
      expression when compared to their luminescent variants. Presently, we conducted
      an in vitro study aiming at the characterization of virulence-related phenotypic
      traits of the wild-type V. harveyi BB120 strain and its isogenic quorum sensing
      mutants before and after switching to the non-luminescent status. We measured the
      production of caseinase, haemolysin and elastase and examined swimming motility
      and biofilm formation. Our results showed that switching from the bioluminescent
      to the non-luminescent state changed the phenotypic physiology or behaviour of V.
      harveyi resulting in alterations in caseinase and haemolytic activities, swimming
      motility and biofilm formation. The switching capacity was to a large extent
      independent from the quorum sensing status, in that quorum sensing mutants were
      equally capable of making the phenotypic switch. 

PMID- 25865124
TI  - Periodic alternating nystagmus. A case report.

PMID- 25865125
TI  - Benign paroxysmal positional vertigo--a review of 101 cases.
AB  - INTRODUCTION AND OBJECTIVE: Benign paroxysmal positional vertigo is one of the
      most common vestibular disorders, with a lifetime prevalence of 2.4%. This study
      aimed to assess age, gender, lesion type and site, association with other
      vestibular diseases, progression and recurrence in a Portuguese population.
      METHODS: This was a retrospective observational study of 101 patients diagnosed
      with benign paroxysmal positional vertigo by the same senior doctor, in a
      tertiary academic hospital, between January 2009 and May 2011. RESULTS: A total
      of 101 cases were pooled, with a mean age of 56.57+/-15.33 years (15-90 years).
      From these, 72.3% were women. The posterior canal was affected in 72.3%, the
      lateral in 24.7%, the anterior in 2% and multiple canals in 1%. Unilateral canal
      and left labyrinth involvement were more frequent. The therapeutic maneuver used
      most was Epley's. Recurrence was observed in 10.9% of the cases. It was
      idiopathic in 83.2% of cases. No association was found between the number of
      maneuvers necessary to treat benign paroxysmal positional vertigo and etiology.
      CONCLUSION: Benign paroxysmal positional vertigo is more frequent in female
      subjects, in the 6th decade and involves preferably the posterior semicircular
      canal of the right labyrinth. In most cases it is idiopathic and treatment with
      repositioning maneuvers has a mean success of 90%. Our results were in accordance
      with the literature; nevertheless, in this study the left labyrinth was most
      affected and the follow-up period was variable.

PMID- 25865126
TI  - Metronomic chemotherapy for advanced pleomorphic adenocarcinoma of the
      nasopharynx.

PMID- 25865127
TI  - Naso-oropharyngeal choristoma (hairy polyps) in adults: A new case, and review of
      the literature.

PMID- 25865128
TI  - Patient tolerance of transoral versus percutaneous thyrohyoid office-based
      injection laryngoplasty: a case-controlled study of forty-one patients.

PMID- 25865129
TI  - Probing residues in the pore-forming (M2) domain of the Cys-loop receptor
      homologue GLIC reveals some unusual features.
AB  - Cys-loop receptors play important roles in signal transduction. The Gloeobacter
      ligand-gated ion channel (GLIC) pore binds similar compounds to Cys-loop receptor
      pores, but has the advantage of known structures in open and closed states. GLIC
      is activated by protons with a pEC50 of 5.4, and has a histidine residue (His
      11') in its pore-forming alpha-helix (M2) which is involved in gating. Here we
      explore the role of this His and other M2 residues using two-electrode voltage
      clamp of mutant receptors expressed in oocytes. We show that 11'His is very
      sensitive to substitution; replacement with a range of amino acids ablates
      function. Similarly altering its location in M2 to the 8', 9', 10', 12', 13' or
      14' positions ablated function. Most substitutions of Ser6' or Ile9' were also
      non-functional, although not Ile9'Leu and Ile9'Val. Unexpectedly, an Ile9'His
      substitution was constitutively active at pH 7, but closed as [H+] increased,
      with a pIC50 of 5.8. Substitution at 2', 5' and 7' had little effect on pEC50.
      Overall the data show Ser6' and His11' are critical for the function of the
      receptor, and thus distinguish the roles of these M2 residues from those of Cys
      loop receptors, where substitutions are mostly well tolerated. These data suggest
      modellers should be aware of these atypical features when using the GLIC pore as
      a model for Cys-loop receptor pores. 

PMID- 25865130
TI  - Exploration of benzamidochromenone derivatives with conformational restrictor as
      interleukin-5 inhibitors.
AB  - Novel amidochromen-4-one analogs 8a-k and 9a-f were prepared and studied for
      their IL-5 inhibitory activity. Among the synthesized compounds, (6-benzamido-2
      cyclohexyl-4-oxo-4H-chromen-3-yl)methyl acetate (8a, 95% inhibition at 30 MUM,
      IC50=6.1 MUM) exhibited potent IL-5 inhibitory activity. The conformational
      restrictor at position 2 like bulky cyclohexyl group is favorable for the
      formation of effective conformer of side chain small ester like acetoxymethyl at
      position 3 of these chromenone analogs 8. In addition the hydrophobic planarity
      of benzamido group at position 6 should be important for the potent IL-5
      inhibitory activity. Since replacing acetoxymethyl moiety with hydroxymethyl
      group at position 3 of chromenone decreases the activity, which indicates that
      the location of hydrogen bonding group should be near 4 atom distances away from
      chromenone ring is more optimum for the activity. Therefore, these
      benzamidochromen-4-one analogs 8 are novel scaffold for finding potent
      interleukin-5 inhibitors.

PMID- 25865131
TI  - Synthesis and biological evaluation of open-chain analogs of cyclic peptides as
      inhibitors of cellular Shp2 activity.
AB  - A series of open-chain analogs of cyclic peptides was designed and synthesized
      using sansalvamide A as a model compound. All compounds exhibited low antitumor
      activity. Furthermore, the evaluation of their inhibitory potency toward IMPDH,
      SHP2, ACHE, proteasome, MAGL, and cathepsin B showed that all of the compounds
      were potent against protein tyrosine phosphatase Shp2. Specifically, compounds
      1a, 1d, 2b, and 2f were found to inhibit SHP2 with IC50 values in the low
      micromolar range and good selectivity. Based on the molecular docking results,
      the binding modes of the chain cyclic peptides in the active center of SHP2 were
      discussed.

PMID- 25865132
TI  - Promising antiproliferative platinum(II) complexes based on imidazole moiety:
      synthesis, evaluation in HCT-116 cancer cell line and interaction with Ctr-1 Met
      rich domain.
AB  - A series of imidazole based platinum(II) complexes were synthesised and evaluated
      for their cytotoxicity in HCT-116 cancer cell line, known for being partially
      resistant to cisplatin but sensitive to oxaliplatin. Lipophilicity was modulated
      by introducing differently long saturated and unsaturated chains at the N1 of the
      imidazole moiety. Pt-I displayed the higher cytotoxic effect achieving a
      IC50=38.0+/-14.1MUM, comparable to the oxaliplatin value. The interaction between
      the imidazole platinum(II) complexes and the octapeptide called Mets7, the
      methionine-rich motif mimicking the N-terminal domain of the yCtr-1, was
      evaluated in order to have a major insight of the uptake and the eventual
      resistance mechanisms for the so-synthesised novel platinum compounds. 

PMID- 25865133
TI  - Diarylsulfonamides and their bioisosteres as dual inhibitors of alkaline
      phosphatase and carbonic anhydrase: Structure activity relationship and molecular
      modelling studies.
AB  - The effect of bioisosteric replacement of carboxamide linking group with
      sulfonamide linking group, on alkaline phosphatase (AP) and carbonic anhydrase
      (CA) inhibition activity of aromatic benzenesulfonamides was investigated. A
      series of carboxamide linked aromatic benzenesulfonamides 1a-1c, 2a-2d and their
      sulfonamide linked bioisosteres 3a-3d, 4a-4d was synthesized and evaluated for
      inhibitory activity against bovine tissue non-specific alkaline phosphatase
      (TNAP), intestinal alkaline phosphatase (IAP) and bCA II. A significant increase
      in CA inhibition activity was observed upon bioisosteric replacement of
      carboxamide linking group with a sulfonamide group. Some of these compounds were
      identified as highly potent and selective AP inhibitors. Compounds 1b, 2b, 3d, 4d
      5b and 5c were found to be selective bTNAP inhibitors, whereas compounds 1a, 1c,
      2a, 2c, 2d, 3a, 3c, 4a, 4b, 4c, 5a were found to be selective bIAP inhibitors.
      For most active AP inhibitor 3b, detailed kinetic studies indicated a competitive
      mode of inhibition against tissue non-specific alkaline phosphatase (TNAP) and
      non-competitive mode of inhibition against intestinal alkaline phosphatase (IAP).
      Molecular docking studies were carried out to rationalize important binding site
      interactions. 

PMID- 25865134
TI  - One-pot Sequential Reactions Featuring a Copper-catalyzed Amination Leading to
      Pyrido[2',1':2,3]imidazo[4,5-c]quinolines and Dihydropyrido[2',1':2,3]imidazo[4,5
      c]quinolines.
AB  - Tetracyclic skeletons combining an imidazo[1,2-a]pyridine moiety with a quinoline
      framework such as pyrido[2',1':2,3]imidazo[4,5-b]quinoline are stimulating
      increasing interests since they are close isosteres of a series of powerful
      antiproliferative compounds. In this paper, we report a novel methodology for the
      synthesis of pyrido[2',1':2,3]imidazo[4,5-c]quinolines through one-pot sequential
      reactions of commercially available or readily obtainable 2-aminopyridines, 2
      bromophenacyl bromides, aqueous ammonia, and aldehydes. Moreover,
      dihydropyrido[2',1':2,3]imidazo[4,5-c]quinolines could also be obtained in a
      similar manner by using various ketones as the substrates in place of aldehydes.
      Notably, the whole procedure combines condensation/amination/cyclization
      reactions in one pot to give complex compounds in a simple and practical manner.
      Compared with literature methods, the synthetic strategy reported herein has the
      advantages of readily available starting materials, structural diversity of
      products, good functional group tolerance, and obviation of step-by-step
      operations. 

PMID- 25865135
TI  - Individual differences in behavioural plasticities.
AB  - Interest in individual differences in animal behavioural plasticities has surged
      in recent years, but research in this area has been hampered by semantic
      confusion as different investigators use the same terms (e.g. plasticity,
      flexibility, responsiveness) to refer to different phenomena. The first goal of
      this review is to suggest a framework for categorizing the many different types
      of behavioural plasticities, describe examples of each, and indicate why using
      reversibility as a criterion for categorizing behavioural plasticities is
      problematic. This framework is then used to address a number of timely questions
      about individual differences in behavioural plasticities. One set of questions
      concerns the experimental designs that can be used to study individual
      differences in various types of behavioural plasticities. Although within
      individual designs are the default option for empirical studies of many types of
      behavioural plasticities, in some situations (e.g. when experience at an early
      age affects the behaviour expressed at subsequent ages), 'replicate individual'
      designs can provide useful insights into individual differences in behavioural
      plasticities. To date, researchers using within-individual and replicate
      individual designs have documented individual differences in all of the major
      categories of behavioural plasticities described herein. Another important
      question is whether and how different types of behavioural plasticities are
      related to one another. Currently there is empirical evidence that many
      behavioural plasticities [e.g. contextual plasticity, learning rates, IIV (intra
      individual variability), endogenous plasticities, ontogenetic plasticities) can
      themselves vary as a function of experiences earlier in life, that is, many types
      of behavioural plasticity are themselves developmentally plastic. These findings
      support the assumption that differences among individuals in prior experiences
      may contribute to individual differences in behavioural plasticities observed at
      a given age. Several authors have predicted correlations across individuals
      between different types of behavioural plasticities, i.e. that some individuals
      will be generally more plastic than others. However, empirical support for most
      of these predictions, including indirect evidence from studies of relationships
      between personality traits and plasticities, is currently sparse and equivocal.
      The final section of this review suggests how an appreciation of the similarities
      and differences between different types of behavioural plasticities may help
      theoreticians formulate testable models to explain the evolution of individual
      differences in behavioural plasticities and the evolutionary and ecological
      consequences of individual differences in behavioural plasticities. 

PMID- 25865136
TI  - Exercise modality effect on oxygen uptake off-transient kinetics at maximal
      oxygen uptake intensity.
AB  - NEW FINDINGS: What is the central question of this study? Do the mechanical
      differences between swimming, rowing, running and cycling have a potential effect
      on the oxygen uptake (VO2) off-kinetics after an exercise sustained until
      exhaustion at 100% of maximal oxygen uptake (VO2max) intensity? What is the main
      finding and its importance? The mechanical differences between exercise modes had
      a potential effect and contributed to distinct amplitude of the fast component
      (higher in running compared with cycling) and time constant (higher in swimming
      compared with rowing and cycling) in the VO2 off-kinetic patterns at 100% of
      VO2max intensity. This suggests that swimmers, unlike rowers and cyclists, would
      benefit more from a longer duration of training intervals after each set of
      exercise performed at VO2max intensity. The kinetics of oxygen uptake (VO2)
      during recovery (off-transient kinetics) for different exercise modes is largely
      unexplored, hampering the prescription of training and recovery to enhance
      performance. The purpose of this study was to compare the VO2 off-transient
      kinetics response between swimmers, rowers, runners and cyclists during their
      specific mode of exercise at 100% of maximal oxygen uptake (VO2max) intensity and
      to examine the on-off symmetry. Groups of swimmers, rowers, runners and cyclists
      (n = 8 per group) performed (i) an incremental exercise protocol to assess the
      velocity or power associated with VO2max (vVO2max or wVO2max, respectively) and
      (ii) a square-wave exercise transition from rest to vVO2max/vVO2maxwVO2maxwVO2max
      until volitional exhaustion. Pulmonary exchange parameters were measured using a
      telemetric portable gas analyser (K4b(2) ; Cosmed, Rome, Italy), and the on- and
      off-transient kinetics were analysed through a double-exponential approach. For
      all exercise modes, both transient periods were symmetrical in shape once they
      had both been adequately fitted by a double-exponential model. However,
      differences were found in the off-kinetic parameters between exercise modes; the
      amplitude of the fast component of the VO2 off-response was higher in running
      compared with cycling (48 +/- 5 and 36 +/- 7 ml kg(-1) min(-1) , respectively; P
      < 0.001), and the time constant of the same phase was higher in swimming compared
      with rowing and cycling (63 +/- 5, 56 +/- 5 and 55 +/- 3 s, respectively; P <
      0.001). Although both phases were well described by a double-exponential model,
      the differences between exercise modes had a potential effect and contributed to
      distinct VO2 off-transient kinetic patterns at 100% of VO2max intensity.

PMID- 25865137
TI  - Substance P activates human eosinophils.

PMID- 25865138
TI  - Essential Roles of Dopamine and Serotonin in Tooth Repair: Functional Interplay
      Between Odontogenic Stem Cells and Platelets.
AB  - Characterizing stem cell intrinsic functions is an ongoing challenge for cell
      therapies. Here, we report that two independent A4 and H8 stem cell lines
      isolated from mouse molar pulp display the overall functions of bioaminergic
      cells. Both clones produce neurotrophins and synthesize, catabolize, store, and
      transport serotonin (5-hydroxytryptamine [5-HT]) and dopamine (DA). They express
      5-HT1D,2B,7 and D1,3 autoreceptors, which render pulpal stem cells competent to
      respond to circulating 5-HT and DA. We show that injury-activated platelets are
      the source of systemic 5-HT and DA necessary for dental repair since natural
      dentin reparation is impaired in two rat models with monoamine storage-deficient
      blood platelets. Moreover, selective inhibition of either D1, D3, 5-HT2B, or 5
      HT7 receptor within the pulp of wild-type rat molars after lesion alters the
      reparative process. Altogether our data argue that 5-HT and DA coreleased by pulp
      injury-activated platelets are critical for stem cell-mediated dental repair
      through 5-HT and DA receptor signalings.

PMID- 25865139
TI  - Antioxidant activity and chemical composition of essential oils of three aromatic
      plants from La Rioja province.
AB  - CONTEXT: The use of many traditional medicinal plants is often hampered by the
      absence of a proper biochemical characterization, which is essential to identify
      the bioactive compounds present in it. The essential oils (EOs) of three native
      species from the La Rioja province were analyzed: Lippia turbinata Griseb and
      Lippia integrifolia (Griseb.) Hieron (Verbenaceae), and Clinopodium gilliesii
      (Benth.) Kuntze (Lamiaceae). OBJECTIVE: The aim of this study was to evaluate
      their EOs antioxidant activity (AA) and their chemical composition. MATERIALS AND
      METHODS: EOs were analyzed by gas chromatography-mass spectrometry (GC-MS). To
      enhance the aqueous solubilization of the EOs, EO-water emulsions were prepared
      (concentration range of 0.1-6 mg mL(-1)). AA was determined using ABTS, DPPH, and
      peroxyl radical scavenging assays, as well as by the beta-carotene bleaching
      test. RESULTS: Piperitenone oxide was a major constituent in L. turbinata,
      pulegone and piperitenone oxide in C. gilliesii, and beta-caryophyllene in L.
      integrifolia. Lippia turbinata EO was the most active ABTS and DPPH radical
      scavenger (SC50 values of 0.40 +/- 0.14 and 0.74 +/- 0.08 mg mL(-1),
      respectively). Clinopodium gilliesii EO exhibited the highest hydrogen peroxide
      scavenging activity (SC25 value = 1.52 +/- 0.27 mg mL(-1)). In the beta-carotene
      assay, L. turbinata EO was more effective at inhibiting lipid peroxidation than
      the other two oils (IC25 value = 0.15 +/- 0.04 mg mL(-1)). CONCLUSION: Our
      results suggest that the AA observed can be justified by the presence of
      oxygenated monoterpenes, mainly piperitenone oxide. Finally, L. turbinata EO
      might be used as a safe natural antioxidant and food preservative in the food and
      cosmetic industries.

PMID- 25865140
TI  - 2013 multistate outbreaks of Cyclospora cayetanensis infections associated with
      fresh produce: focus on the Texas investigations.
AB  - The 2013 multistate outbreaks contributed to the largest annual number of
      reported US cases of cyclosporiasis since 1997. In this paper we focus on
      investigations in Texas. We defined an outbreak-associated case as laboratory
      confirmed cyclosporiasis in a person with illness onset between 1 June and 31
      August 2013, with no history of international travel in the previous 14 days.
      Epidemiological, environmental, and traceback investigations were conducted. Of
      the 631 cases reported in the multistate outbreaks, Texas reported the greatest
      number of cases, 270 (43%). More than 70 clusters were identified in Texas, four
      of which were further investigated. One restaurant-associated cluster of 25 case
      patients was selected for a case-control study. Consumption of cilantro was most
      strongly associated with illness on meal date-matched analysis (matched odds
      ratio 19.8, 95% confidence interval 4.0-infinity). All case-patients in the other
      three clusters investigated also ate cilantro. Traceback investigations converged
      on three suppliers in Puebla, Mexico. Cilantro was the vehicle of infection in
      the four clusters investigated; the temporal association of these clusters with
      the large overall increase in cyclosporiasis cases in Texas suggests cilantro was
      the vehicle of infection for many other cases. However, the paucity of
      epidemiological and traceback information does not allow for a conclusive
      determination; moreover, molecular epidemiological tools for cyclosporiasis that
      could provide more definitive linkage between case clusters are needed. 

PMID- 25865141
TI  - Functional diagnostic parameters for arteriovenous fistula.
AB  - The inability to detect the arteriovenous fistula (AVF) dysfunction in a timely
      manner under the current surveillance programs, which are based on either
      diameter (d), flow rate (Q), or pressure (p) measurements, is one of the major
      challenges of dialysis treatment. Thus, our aim is to introduce new functional
      diagnostic parameters that can better predict AVF functionality status. Six AVFs
      were created between the femoral arteries and veins of three pigs, each pig
      having two AVFs on either limb. Flow fields and pressure drop (Deltap) in AVFs
      were obtained via numerical analysis utilizing the CT scan and Doppler ultrasound
      data at 2D (D: days), 7D, and 28D postsurgery. The dataset included 16 (two pigs
      [four AVFs] for three time points, and one pig [two AVFs] for two time points)
      repeated measurements over time, and the statistical analysis was done using a
      mixed model. To evaluate the nature of pressure drop-flow relationships in AVFs,
      the Deltap was correlated with the average velocity at proximal artery (v) and
      also the corresponding scaled velocity (v*) by the curvature ratio of anastomotic
      segment. Based on these relationships, two new functional diagnostic parameters,
      including the nonlinear pressure drop coefficient (Cp ; pressure drop divided by
      dynamic pressure at proximal artery) and the linear resistance index (R; pressure
      drop divided by velocity at proximal artery), were introduced. The diagnostic
      parameters that were calculated based on scaled velocity are represented as R*
      and Cp *. A marginal (P = 0.1) increase in d from 2D (5.4 +/- 0.7 mm) to 7D (6.8
      +/- 0.7 mm), along with a significant increase in Q (2D: 967 +/- 273 mL/min; 7D:
      1943 +/- 273 mL/min), was accompanied by an almost unchanged Deltap over this
      time period (2D: 16.42 +/- 4.6 mm Hg; 7D: 16.40 +/- 4.6 mm Hg). However, the
      insignificant increase in d and Q from 7D to 28D (d = 7.8 +/- 0.8 mm; Q = 2181 +/
      378 mL/min) was accompanied by the elevation in Deltap (24.6 +/- 6.5 mm Hg). The
      functional diagnostic parameters, R and Cp , decreased from 2D (R = 22.4 +/- 2.8
      mm Hg/m/s; Cp  = 12.0 +/- 2.6) to 7D (R = 20.8 +/- 2.8 mm Hg/m/s; Cp  = 8.1 +/-
      2.6), and then increased from 7D to 28D (R = 35.5 +/- 5.7 mm Hg/m/s; Cp  = 17.5
      +/- 3.6) with a marginal significance. However, when the scaled velocity was used
      to calculate R* and Cp *, the increase in diagnostic parameters from 7D to 28D
      achieved statistical significance (P < 0.05). In summary, although the
      differences in the hemodynamic parameters (d, Q, and Deltap) from 7D to 28D were
      insignificant, changes in their combined effects in the form of diagnostic
      parameters were significant. Therefore, the functional diagnostic parameters are
      capable of better distinguishing changes in the hemodynamic variations, and thus,
      could be promising endpoints to diagnose the functionality of AVFs over time.

PMID- 25865142
TI  - Developmental timing of sodium perchlorate exposure alters angiogenesis, thyroid
      follicle proliferation and sexual maturation in stickleback.
AB  - Perchlorate, a common aquatic contaminant, is well known to disrupt homeostasis
      of the hypothalamus-pituitary-thyroid axis. This study utilizes the threespine
      stickleback (Gasterosteus aculeatus) fish to determine if perchlorate exposure
      during certain windows of development has morphological effects on thyroid and
      gonads. Fish were moved from untreated water to perchlorate-contaminated water
      (30 and 100mg/L) starting at 0, 3, 7, 14, 21, 42, 154 and 305 days post
      fertilization until approximately one year old. A reciprocal treatment (fish in
      contaminated water switched to untreated water) was conducted on the same
      schedule. Perchlorate exposure increased angiogenesis and follicle proliferation
      in thyroid tissue, delayed gonadal maturity, and skewed sex ratios toward males;
      effects depended on concentration and timing of exposure. This study demonstrates
      that perchlorate exposure beginning during the first 42 days of development has
      profound effects on stickleback reproductive and thyroid tissues, and by
      implication can impact population dynamics. Long-term exposure studies that
      assess contaminant effects at various stages of development provide novel
      information to characterize risk to aquatic organisms, to facilitate management
      of resources, and to determine sensitive developmental windows for further study
      of underlying mechanisms.

PMID- 25865144
TI  - Spatial attention enhances object coding in local and distributed representations
      of the lateral occipital complex.
AB  - The modulation of neural activity in visual cortex is thought to be a key
      mechanism of visual attention. The investigation of attentional modulation in
      high-level visual areas, however, is hampered by the lack of clear tuning or
      contrast response functions. In the present functional magnetic resonance imaging
      study we therefore systematically assessed how small voxel-wise biases in object
      preference across hundreds of voxels in the lateral occipital complex were
      affected when attention was directed to objects. We found that the strength of
      attentional modulation depended on a voxel's object preference in the absence of
      attention, a pattern indicative of an amplificatory mechanism. Our results show
      that such attentional modulation effectively increased the mutual information
      between voxel responses and object identity. Further, these local modulatory
      effects led to improved information-based object readout at the level of multi
      voxel activation patterns and to an increased reproducibility of these patterns
      across repeated presentations. We conclude that attentional modulation enhances
      object coding in local and distributed object representations of the lateral
      occipital complex. 

PMID- 25865143
TI  - Arousal transitions in sleep, wakefulness, and anesthesia are characterized by an
      orderly sequence of cortical events.
AB  - Many aspects of brain function are influenced by modulatory processes, including
      arousal. The most abrupt changes in arousal occur at the wake-sleep transition
      and at the induction of anesthetic conditions. They are accompanied by major
      electrophysiological changes, including an emergence of low-frequency (sleep
      like) activity and a loss of mid-frequency (wake-like) activity that has been
      linked to feedback processes of the brain. Nevertheless, the causal relationship
      between these two types of electrophysiological changes, as well as the cortical
      mechanisms underlying changes in arousal and consciousness, remain poorly
      understood. To address this, we studied spontaneous electro-cortical activity
      during arousal changes in macaques. During sleep and at loss of consciousness
      induced by propofol anesthesia, we identified a prototypical sequence of cortical
      events in which the loss of mid-frequency activity preceded, by seconds, the
      increases in low-frequency activity. Furthermore, in visual areas, an influence
      of mid-frequency change onto high-frequency activity was observed across visual
      hierarchy. These results are consistent with the notion that drops in arousal and
      consciousness are facilitated by a release of feedback cortical inhibition. 

PMID- 25865145
TI  - Controversial Role of Toll-like Receptor 4 in Adult Stem Cells.
AB  - Adult or somatic stem cells are tissue-resident cells with the ability to
      proliferate, exhibit self-maintenance as well as to generate new cells with the
      principal phenotypes of the tissue in response to injury or disease. Due to their
      easy accessibility and their potential use in regenerative medicine, adult stem
      cells raise the hope for future personalisable therapies. After infection or
      during injury, they are exposed to broad range of pathogen or damage-associated
      molecules leading to changes in their proliferation, migration and
      differentiation. The sensing of such damage and infection signals is mostly
      achieved by Toll-Like Receptors (TLRs) with Toll-like receptor 4 being
      responsible for recognition of bacterial lipopolysaccharides (LPS) and endogenous
      danger-associated molecular patterns (DAMPs). In this review, we examine the
      current state of knowledge on the TLR4-mediated signalling in different adult
      stem cell populations. Specifically, we elaborate on the role of TLR4 and its
      ligands on proliferation, differentiation and migration of mesenchymal stem
      cells, hematopoietic stem cells as well as neural stem cells. Finally, we discuss
      conceptual and technical pitfalls in investigation of TLR4 signalling in stem
      cells.

PMID- 25865146
TI  - Pericytes: Properties, Functions and Applications in Tissue Engineering.
AB  - Mesenchymal stem cells (MSCs) are one of the most studied adult stem cells and in
      recent years. They have become attractive agents/cell source for cellular therapy
      and regenerative medicine applications. During investigations about their origin,
      researchers hypothesized that perivascular regions are the common anatomical
      regions where MSCs come from and perivascular cells like pericytes (PCs) (Rouget
      cells, mural cells) are in vivo counterparts of MSCs. Beside capillaries and
      microvessels as their most common locations, PCs are also found in large vessels
      (arteries and veins). They can be isolated from several tissues and organs
      particularly from retina and brain. There are different approaches about their
      isolation, characterization and culture but there has been no common protocol yet
      because of the lack of defined PC-specific marker. They make special contact with
      endothelial cells in the basement membrane and have very important functions in
      several tissues and organs. They participate in vascular development,
      stabilization, maturation, and remodeling, blood pressure control, endothelial
      cell proliferation and differentiation, contractility of vascular smooth muscle
      cells, wound healing, vasculogenesis and angiogenesis, long-term maintenance of
      hematopoietic stem cells in bone marrow niche. Their multipotential
      differentiation capacity and participation in many events in the body make PCs
      preferred cells in tissue engineering applications including 3D blood-brain
      barrier models, skeletal muscle constructs, bone tissue engineering and tissue
      engineered vascular grafts.

PMID- 25865147
TI  - A 22-year follow-up of an endodontic implant.
AB  - Root fractures in the middle and apical thirds of the root are treated by
      repositioning and for approximately 6 weeks of immobilization while those in the
      cervical third are immobilized for 3 months. Even though the results are good,
      some root-fractured teeth are lost and replaced by dental implants or fixed
      partial dentures. One historic but effective treatment option for those root
      fractures with unfavorable crown to root ratios is an endodontic implant in
      middle and apical third root fractures. This method offers immediate stable
      fixation of a crown and its coronal root segment to the underlying alveolar bone.
      This report documents the long-term survival of a tooth treated with an
      endodontic implant. A 25-year-old male patient presented following a bicycle
      accident with a dislocated unfavorable root fracture in the middle third. The
      crown with the coronal root segment was secured to the bone using a commercially
      available endodontic implant. The apical part of the root was removed. Although
      the clinical and radiological follow-up results of the endodontic implant
      demonstrated a good clinical function and little bone loss, the implant
      ultimately had to be removed after 22 years of service due to pain and increasing
      mobility.

PMID- 25865148
TI  - Impact of a half marathon on cellular immune system, pro-inflammatory cytokine
      levels, and recovery behavior of breast cancer patients in the aftercare compared
      to healthy controls.
AB  - INTRODUCTION: Exercise has beneficial effects on cancer prevention as well as on
      prognosis of patients with cancer. To optimize the outcomes of exercise programs,
      more knowledge about the underlying mechanisms is needed. This study investigates
      the short-term effects of a half marathon on immune cell proportions, pro
      inflammatory cytokine levels, and recovery behavior of patients with breast
      cancer in the aftercare compared to healthy controls. METHODS: Nine patients with
      breast cancer in the aftercare and 9 healthy age-matched controls participated in
      a half marathon. Blood samples were collected before, after, and 24 h after the
      run. Immune status was measured by flow cytometer analysis, while serum levels of
      the pro-inflammatory cytokines TNF-alpha, IL-6, and MIF were assessed using
      ELISA. Recovery behavior was determined using an ADL monitor. RESULTS: Both
      groups showed a similar recovery behavior and time courses in changes of
      granulocytes, monocytes, lymphocytes, and cytokine serum levels. Patients
      revealed increased proportions of cytotoxic and memory T cells, whereas helper
      and naive T cells were decreased compared to healthy controls. Naive and memory T
      cell proportions were not affected by the intervention. CONCLUSIONS: Patients
      with breast cancer in the aftercare and healthy subjects show a similarly
      recovery behavior and immune response to the intervention. The detected
      differences in T-cell subsets need further investigation. Based on the results of
      the study, we hypothesize that immune cell subsets with known relevance in cancer
      were mobilized through the intervention. We confirm that the hypothesis of a
      midterm anti-inflammatory effect of exercise is also valid for patients with
      breast cancer in the aftercare.

PMID- 25865149
TI  - Classifying insulin regimens--difficulties and proposal for comprehensive new
      definitions.
AB  - Modern insulin regimens for the treatment of type 1 diabetes are highly
      individualized. The concept of an individually tailored medicine accounts for a
      broad variety of different insulin regimens applied. Despite clear
      recommendations for insulin management in children and adolescents with type 1
      diabetes there is little distinctiveness about concepts and the nomenclature is
      confusing. Even among experts similar terms are used for different strategies.
      The aim of our review--based on the experiences of the Hvidoere Study Group (HSG)
      -is to propose comprehensive definitions for current insulin regimens reflecting
      current diabetes management in childhood and adolescence. The HSG--founded in
      1994--is an international group representing 24 highly experienced pediatric
      diabetes centers, from Europe, Japan, North America and Australia. Different
      benchmarking studies of the HSG revealed a broad variety of insulin regimens
      applied in each center, respectively. Furthermore, the understanding of insulin
      regimens has been persistently different between the centers since more than 20
      yr. Not even the terms 'conventional' and 'intensified therapy' were used
      consistently among all members. Besides the concepts 'conventional' and
      'intensified', several other terms for the characterization of insulin regimens
      are in use: Basal Bolus Concept (BBC), multiple daily injections (MDI), and
      flexible insulin therapy (FIT) are most frequently used, although none of these
      expressions is clearly or consistently defined. The proposed new classification
      for insulin management will be comprehensive, simple, and catchy. Currently
      available terms were included. This classification may offer the opportunity to
      compare therapeutic strategies without the currently existing confusion on the
      insulin regimen.

PMID- 25865150
TI  - Phylogenetic community ecology of soil biodiversity using mitochondrial
      metagenomics.
AB  - High-throughput DNA methods hold great promise for the study of taxonomically
      intractable mesofauna of the soil. Here, we assess species diversity and
      community structure in a phylogenetic framework, by sequencing total DNA from
      bulk specimen samples and assembly of mitochondrial genomes. The combination of
      mitochondrial metagenomics and DNA barcode sequencing of 1494 specimens in 69
      soil samples from three geographic regions in southern Iberia revealed >300
      species of soil Coleoptera (beetles) from a broad spectrum of phylogenetic
      lineages. A set of 214 mitochondrial sequences longer than 3000 bp was generated
      and used to estimate a well-supported phylogenetic tree of the order Coleoptera.
      Shorter sequences, including cox1 barcodes, were placed on this mitogenomic tree.
      Raw Illumina reads were mapped against all available sequences to test for
      species present in local samples. This approach simultaneously established the
      species richness, phylogenetic composition and community turnover at species and
      phylogenetic levels. We find a strong signature of vertical structuring in soil
      fauna that shows high local community differentiation between deep soil and
      superficial horizons at phylogenetic levels. Within the two vertical layers,
      turnover among regions was primarily at the tip (species) level and was stronger
      in the deep soil than leaf litter communities, pointing to layer-mediated drivers
      determining species diversification, spatial structure and evolutionary assembly
      of soil communities. This integrated phylogenetic framework opens the application
      of phylogenetic community ecology to the mesofauna of the soil, among the most
      diverse and least well-understood ecosystems, and will propel both theoretical
      and applied soil science.

PMID- 25865151
TI  - New Oral Anticoagulants (NOAC) Studies in the Ideal and the Real World - Needs of
      Prospective Observational Studies.

PMID- 25865153
TI  - The correlation of clinical efficacy, serum trough levels and antidrug antibodies
      in ustekinumab-treated patients with psoriasis in a clinical-practice setting.

PMID- 25865154
TI  - RETRACTED ARTICLE: Neuromuscular electrical stimulation in critically ill
      patients in the intensive care unit: a systematic review.

PMID- 25865155
TI  - Locating and classifying fluorescent tags behind turbid layers using time
      resolved inversion.
AB  - The use of fluorescent probes and the recovery of their lifetimes allow for
      significant advances in many imaging systems, in particular, medical imaging
      systems. Here we propose and experimentally demonstrate reconstructing the
      locations and lifetimes of fluorescent markers hidden behind a turbid layer. This
      opens the door to various applications for non-invasive diagnosis, analysis,
      flowmetry and inspection. The method is based on a time-resolved measurement that
      captures information about both fluorescence lifetime and spatial position of the
      probes. To reconstruct the scene, the method relies on a sparse optimization
      framework to invert time-resolved measurements. This wide-angle technique does
      not rely on coherence, and does not require the probes to be directly in line of
      sight of the camera, making it potentially suitable for long-range imaging. 

PMID- 25865152
TI  - Ventral tegmental area cholinergic mechanisms mediate behavioral responses in the
      forced swim test.
AB  - Recent studies revealed a causal link between ventral tegmental area (VTA) phasic
      dopamine (DA) activity and pro-depressive and antidepressant-like behavioral
      responses in rodent models of depression. Cholinergic activity in the VTA has
      been demonstrated to regulate phasic DA activity, but the role of VTA cholinergic
      mechanisms in depression-related behavior is unclear. The goal of this study was
      to determine whether pharmacological manipulation of VTA cholinergic activity
      altered behavioral responding in the forced swim test (FST) in rats. Here, male
      Sprague-Dawley rats received systemic or VTA-specific administration of the
      acetylcholinesterase inhibitor, physostigmine (systemic; 0.06 or 0.125mg/kg,
      intra-cranial; 1 or 2MUg/side), the muscarinic acetylcholine receptor (AChR)
      antagonist scopolamine (2.4 or 24MUg/side), or the nicotinic AChR antagonist
      mecamylamine (3 or 30MUg/side), prior to the FST test session. In control
      experiments, locomotor activity was also examined following systemic and intra
      cranial administration of cholinergic drugs. Physostigmine administration, either
      systemically or directly into the VTA, significantly increased immobility time in
      FST, whereas physostigmine infusion into a dorsal control site did not alter
      immobility time. In contrast, VTA infusion of either scopolamine or mecamylamine
      decreased immobility time, consistent with an antidepressant-like effect.
      Finally, the VTA physostigmine-induced increase in immobility was blocked by co
      administration with scopolamine, but unaltered by co-administration with
      mecamylamine. These data show that enhancing VTA cholinergic tone and blocking
      VTA AChRs has opposing effects in FST. Together, the findings provide evidence
      for a role of VTA cholinergic mechanisms in behavioral responses in FST. 

PMID- 25865157
TI  - Enigmatic ion-exchange behavior of myo-inositol phosphates.
AB  - The separation of myo-inositol mono-, di-, tri-, tetra-, pentakis-, and
      hexakisphosphate (InsP1, InsP2, InsP3, InsP4, InsP5, InsP6) was carried out using
      hydroxide eluent ion chromatography. Acid hydrolysis of InsP6 (phytate) was used
      to prepare a distribution of InsPs, ranging from InsP1 to InsP5's and including
      unhydrolyzed InsP6. Counting all possible positional isomers (many of which have
      stereoisomers that will not be separable by conventional ion exchange), 40
      chromatographically separable peaks are possible; up to 22 were separated and
      identified by mass spectrometry. InsPs show unusual ion-exchange behavior in two
      respects: (a) the retention order is not monotonically related with the charge on
      the ion and (b) at the same hydroxide eluent concentration, retention is greatly
      dependent on the eluent metal cation. The retention of InsP3-InsP6 was determined
      to be controlled by steric factors while elution was influenced by eluent cation
      complexation. These highly phosphorylated InsPs have a much greater affinity for
      alkali metals (Li(+) > Na(+) > K(+)) than quaternary ammonium ions. This
      difference in cation affinity was exploited to improve separation through the use
      of a tetramethylammonium hydroxide-sodium hydroxide gradient. 

PMID- 25865156
TI  - l-Arginine Attenuates Cardiac Dysfunction, But Further Down-Regulates alpha
      Myosin Heavy Chain Expression in Isoproterenol-Induced Cardiomyopathy.
AB  - In view of previously reported increased capacity for nitric oxide production, we
      suggested that l-arginine (ARG), the nitric oxide synthase (NOS) substrate,
      supplementation would improve cardiac function in isoproterenol (ISO)-induced
      heart failure. Male Wistar rats were treated with ISO for 8 days (5 mg/kg/day,
      i.p.) or vehicle. ARG was given to control (ARG) and ISO-treated (ISO+ARG) rats
      in water (0.4 g/kg/day). ISO administration was associated with 40% mortality,
      ventricular hypertrophy, decreased heart rate, left ventricular dysfunction,
      fibrosis and ECG signs of ischaemia. RT-PCR showed increased mRNA levels of
      cardiac hypertrophy marker atrial natriuretic peptide, but not BNP, decreased
      expression of myosin heavy chain isoform MYH6 and unaltered expression of
      pathological MYH7. ISO increased the protein levels of endothelial nitric oxide
      synthase, but at the same time it markedly up-regulated mRNA and protein levels
      of gp91phox, a catalytical subunit of superoxide-producing NADPH oxidase.
      Fibrosis was markedly increased by ISO. ARG treatment moderately ameliorated left
      ventricular dysfunction, but was without effect on cardiac hypertrophy and
      fibrosis. Combination of ISO and ARG led to a decrease in cav-1 expression, a
      further increase in MYH7 expression and a down-regulation of MYH6 that inversely
      correlated with gp91phox mRNA levels. Although ARG, at least partially, improved
      ISO-impaired basal left ventricular systolic function, it failed to reduce
      cardiac hypertrophy, fibrosis, oxidative stress and mortality. The protection of
      contractile performance might be related to increased capacity for nitric oxide
      production and the up-regulation of MYH7 which may compensate for the marked down
      regulation of the major MYH6 isoform. 

PMID- 25865158
TI  - Inpatient admissions from the ED for adults with injuries: the role of clinical
      and nonclinical factors.
AB  - INTRODUCTION: Inpatient hospital costs represent nearly a third of heath care
      spending. The proportion of inpatients visits that originate in the emergency
      department (ED) has been growing, approaching half of all inpatient admissions.
      Injury is the most common reason for adult ED visits, representing nearly one
      quarter of all ED visits. OBJECTIVE: The objective was to explore the association
      of clinical and nonclinical factors with the decision to admit ED patients with
      injury. RESEARCH DESIGN AND PARTICIPANTS: This is a retrospective cohort study of
      injury-related ED encounters by adults in select states in 2009. We limited the
      study to ED visits of persons with moderately severe injuries. We used logistic
      regression to calculate the marginal effects, estimating 4 equations to account
      for different risk patterns for older and younger adults, and types of injuries.
      Regression models controlled for comorbidities, injury characteristics,
      demographic characteristics, and state fixed effects. RESULTS: Injury location,
      type, and mechanism and comorbidities had large effects on hospitalization rates
      as expected. We found higher inpatient admission rates by level of trauma center
      designation and hospital size, but findings differed by age and type of injury.
      For younger adults, patients with private insurance and patients who traveled
      more than 30 miles were more likely to be admitted. CONCLUSIONS: There is great
      variation in inpatient admission decisions for moderately injured patients in the
      ED. Decisions appear to be dominated by clinical factors such as injury
      characteristics and comorbidities; however, nonclinical factors, such as type of
      insurance, hospital size, and trauma center designation, also play an important
      role.

PMID- 25865159
TI  - Electrocardiographic findings in patients with pulmonary embolism.

PMID- 25865160
TI  - Evaluation of analgesic effects of ketamine through sub-dissociative dosing in
      the ED.

PMID- 25865161
TI  - Fluorescence-detected magnetic field effects on radical pair reactions from
      femtolitre volumes.
AB  - We show that the effects of applied magnetic fields on radical pair reactions can
      be sensitively measured from sample volumes as low as ~100 femtolitres using
      total internal reflection fluorescence microscopy. Development of a fluorescence
      based microscope method is likely to be a key step in further miniaturisation
      that will allow detection of magnetic field effects on single molecules. 

PMID- 25865162
TI  - Molecular detection of zoonotic bartonellae (B. henselae, B. elizabethae and B.
      rochalimae) in fleas collected from dogs in Israel.
AB  - Fleas represent an acknowledged burden on dogs worldwide. The characterization of
      flea species infesting kennel dogs from two localities in Israel (Rehovot and
      Jerusalem) and their molecular screening for Bartonella species (Rhizobiales:
      Bartonellaceae) was investigated. A total of 355 fleas were collected from 107
      dogs. The fleas were morphologically classified and molecularly screened
      targeting the Bartonella 16S-23S internal transcribed spacer (ITS). Of the 107
      dogs examined, 80 (74.8%) were infested with Ctenocephalides canis (Siphonaptera:
      Pulicidae), 68 (63.6%) with Ctenocephalides felis, 15 (14.0%) with Pulex irritans
      (Siphonaptera: Pulicidae) and one (0.9%) with Xenopsylla cheopis (Siphonaptera:
      Pulicidae). Fleas were grouped into 166 pools (one to nine fleas per pool)
      according to species and host. Thirteen of the 166 flea pools (7.8%) were found
      to be positive for Bartonella DNA. Detected ITS sequences were 99-100% similar to
      those of four Bartonella species: Bartonella henselae (six pools); Bartonella
      elizabethae (five pools); Bartonella rochalimae (one pool), and Bartonella bovis
      (one pool). The present study indicates the occurrence of a variety of flea
      species in dogs in Israel; these flea species are, in turn, carriers of several
      zoonotic Bartonella species. Physicians, veterinarians and public health workers
      should be aware of the presence of these pathogens in dog fleas in Israel and
      preventive measures should be implemented. 

PMID- 25865163
TI  - Ecosystems in four dimensions.

PMID- 25865164
TI  - Reducing the gaps in our understanding of the global terrestrial carbon cycle.

PMID- 25865165
TI  - Chloroplast transcription, untangling the Gordian Knot.

PMID- 25865166
TI  - Invasion is sweet.

PMID- 25865167
TI  - The role of polymer size and hydrophobic end-group in PEG-protein interaction.
AB  - We investigated the interaction between polyethylene (glycol) (PEG) and human
      (HSA) and bovine serum albumin (BSA) in aqueous solution, using multiple
      spectroscopic methods and molecular modeling. The two important polymer
      characteristics, size and PEG hydrophobic end-group are studied in order to
      determine the effect of each one on PEG-protein interaction. The bindings of PEG
      and mPEG-anthracene with serum albumins occur via hydrophobic and H-bonding
      contacts with the binding affinity PEG-6000>mPEG-anthracene>PEG-3000 for BSA and
      EG-6000>PEG-3000>mPEG-anthracene for HSA. Modeling showed different protein
      binding sites are involved in PEG-BSA and PEG-HSA complexes. Several H-bonding
      systems between PEG and different amino acids are stabilizing polymer-protein
      complexes. The free binding energies of -6.48 (PEG-BSA) and -6.36 kcal/mol (PEG
      HSA) showed that the interaction process is spontaneous at room temperature.
      Minor alterations of protein alpha-helix and beta-sheet structures were observed
      upon PEG complexation.

PMID- 25865168
TI  - IgG/IgA pemphigus representing pemphigus vegetans caused by low titres of IgG and
      IgA antibodies to desmoglein 3 and IgA antibodies to desmocollin 3.

PMID- 25865169
TI  - 3D FEA of Hollow and Solid Design Zirconia Dental Dowels.
AB  - PURPOSE: The aim of this study was to evaluate the stress distribution of hollow
      and solid design zirconia dowels. MATERIALS AND METHODS: Finite element analysis
      (FEA) was used to investigate the influence of different dowel designs on the
      stress distribution of zirconia dowels. The coronal diameter of the dowel was 2.2
      mm, the apical diameter was 1.8 mm, and the length was 15 mm. The diameter of the
      hollow space was 1.2 mm. Occlusal forces (both parallel and oblique) of 100 N
      were applied from the wider edge of the dowels simulating loads acting on the
      incisor during clenching and incising. The results were expressed in terms of von
      Mises criteria. RESULTS: FEA revealed differences in stress distribution. During
      parallel load, the maximum tensile stress of the hollow design (89.40 MPa) was
      greater than the solid design (43.30 MPa). During oblique load, the maximum
      tensile stress of the hollow design (1437.90 MPa) was greater than the solid
      design (917.96 MPa). The maximum deformation was observed in the coronal part of
      the dowel in both designs under the two load directions. CONCLUSIONS: FEA results
      showed that the hollow design zirconia dowels presented higher tensile stress.

PMID- 25865170
TI  - Assessment of the relationship between hypoglycaemia awareness and autonomic
      function following islet cell/pancreas transplantation.
AB  - BACKGROUND: This study assesses the autonomic function of patients who have
      regained awareness of hypoglycaemia following islet cell or whole pancreas
      transplant. METHODS: Five patients with type 1 diabetes and either islet cell
      (four patients) or whole pancreas (one patient) transplant were assessed. These
      patients were age-matched and gender-matched to five patients with type 1
      diabetes without transplant and preserved hypoglycaemia awareness and five
      healthy control participants without diabetes. All participants underwent (i) a
      battery of five cardiovascular autonomic function tests, (ii) quantitative
      sudomotor axonal reflex testing, and (iii) sympathetic skin response testing.
      RESULTS: Total recorded hypoglycaemia episodes per month fell from 76 pre
      transplant to 13 at 0- to 3-month post-transplant (83% reduction). The percentage
      of hypoglycaemia episodes that patients were unaware of decreased from 97 to 69%
      at 0-3 months (p < 0.001, Fisher's exact test) and to 20% after 12 months (p <
      0.0001, Fisher's exact test). This amelioration was maintained at the time of
      testing (mean time: 4.1 years later, range: 2-6 years). Presence of significant
      autonomic neuropathy was seen in all five transplanted patients (at least 2/3
      above modalities abnormal) but in only one of the patients with diabetes without
      transplantation. CONCLUSIONS: The long-term maintenance of hypoglycaemia
      awareness that returns after islet cell/pancreas transplantation in patients with
      diabetes is not prevented by significant autonomic neuropathy and is better
      accounted for by other factors such as reversal of hypoglycaemia-associated
      autonomic failure.

PMID- 25865171
TI  - Arrestant property of recently manipulated soil on Macrotermes michaelseni as
      determined through visual tracking and automatic labeling of individual termite
      behaviors.
AB  - The construction of termite nests has been suggested to be organized by a
      stigmergic process that makes use of putative cement pheromone found in saliva
      and recently manipulated soil ("nest material"), hypothesized to specifically
      induce material deposition by workers. Herein, we tracked 100 individuals placed
      in arenas filled with a substrate of half nest material, half clean soil, and
      used automatic labeling software to identify behavioral states. Our findings
      suggest that nest material acts to arrest termites; termites prefer to spend time
      on nest material when compared against clean soil. Residency time was
      significantly greater, and all construction behaviors occurred significantly more
      often on nest material. The arrestant function of nest material must be accounted
      for in experiments that seek semiochemical cues for the organization of labor.
      Future research will focus on the manner in which termites combine olfaction with
      tactile cues as well as other organizing factors during construction. 

PMID- 25865172
TI  - Distribution, partition and removal of polycyclic aromatic hydrocarbons (PAHs)
      during coking wastewater treatment processes.
AB  - In this study, we report the performance of a full-scale conventional activated
      sludge (A-O1-O2) treatment in eliminating polycyclic aromatic hydrocarbons
      (PAHs). Both aqueous and solid phases along with the coking wastewater treatment
      processes were analyzed for the presence of 18 PAHs. It was found that the target
      compounds occurred widely in raw coking wastewater, treated effluent and sludge
      samples. In the coking wastewater treatment system, 4-5 ring PAHs were the
      dominant compounds, while 4 rings PAHs predominated in the sludge samples. Over
      98% of the PAH removal was achieved in the coking wastewater treatment plant
      (WWTP), with the total concentration of PAHs being 21.3 +/- 1.9 MUg L(-1) in the
      final effluent. During the coking wastewater treatment processes, the association
      of the lower molecular weight PAH with suspended solids was generally less than
      60%, while the association of higher molecular weight PAHs was greater than 90%.
      High distribution efficiencies (Kdp and Kds) were found, suggesting that
      adsorption was the potential removal pathway of PAHs. Finally, the mass balances
      of PAHs in various stages of the coking WWTP were obtained, and the results
      indicated that adsorption to sludge was the main removal pathway for PAHs in the
      coking wastewater treatment processes. 

PMID- 25865173
TI  - In the Blink of an I: On Delayed but Identical Subjective Reactions and Their
      Effect on Self-Interested Behavior.
AB  - People believe that they have shared an identical subjective experience--that
      they have I-shared--when they react identically and simultaneously to the same
      stimulus. Despite growing evidence for I-sharing, researchers have yet to ask
      whether simultaneity really makes a difference. We test the importance of
      simultaneity for I-sharing effects. Participants played prisoner's dilemma with
      someone who shared their subjective self, their objective self, or neither. Some
      participants learned this information immediately; others, after a short delay.
      Time delay decreased cooperation in the subjective similarity condition, but not
      in the objective similarity or neither conditions. These findings underscore the
      importance of simultaneity for I-sharing effects and highlight the implications
      of I-sharing for cooperation and self-interested behavior.

PMID- 25865174
TI  - Therapeutic hypothermia in acute liver failure: A multicenter retrospective
      cohort analysis.

PMID- 25865175
TI  - Frequent self-weighing as part of a constellation of healthy weight control
      practices in young adults.
AB  - OBJECTIVE: Frequent self-weighing is linked with weight management success, but
      concern has been raised about its possible association with unhealthy practices.
      This study examined the association of self-weighing with other weight control
      behaviors in a sample for whom frequent weighing might be questioned--namely,
      normal-weight or overweight (BMI of 21-29.9) young adults (age 18-35). METHODS:
      Participants (N = 583; mean [SD] age = 27.7 [4.4]; BMI = 25.4 [2.6]) entering the
      Study of Novel Approaches to Weight Gain Prevention (SNAP) completed objective
      measures of weight and physical activity and self-reported weight history, use of
      healthy and unhealthy weight control strategies, depressive symptoms, and dietary
      intake. RESULTS: Daily self-weighing was reported by 11% of participants, and 23%
      weighed several times per week. Frequent weighing was not associated with current
      BMI, gender, or age but was associated with being further below one's highest
      weight, history of dieting, and perceived difficulty maintaining weight. Frequent
      weighing was associated with healthy weight management strategies, but not with
      unhealthy practices or depressive symptoms. CONCLUSIONS: In this sample, frequent
      self-weighing appears to be part of a constellation of healthy weight control
      behaviors used to counteract a perceived tendency toward weight gain. SNAP follow
      up will determine whether frequent self-weighing helps prevent weight gain.

PMID- 25865176
TI  - Fast and Online Determination of Five Avermectin Residues in Foodstuffs of Plant
      and Animal Origin Using Reusable Polymeric Monolithic Extractor Coupled with LC
      MS/MS.
AB  - A hydrophobic monolith (10 mm * 2.1 mm i.d.) was developed as a reusable online
      solid-phase extraction (SPE) sorbent coupled with LC-MS/MS for the rapid
      determination of five avermectin residues in foodstuffs of both plant and animal
      origin. The online SPE was achieved using a 10 mmol/L ammonium acetate solution
      as the loading solvent, and acetonitrile (MeCN) was selected for the washing
      step. After being transferred from the monolith into a C18 analytical column
      using MeCN, the analytes were analyzed by LC-MS/MS using MeCN/0.1% NH4OH (10:90,
      v/v) as the mobile phase. The detection limit was 2 MUg/kg for five avermectins,
      and the recoveries in fresh pear, chili seed, bovine muscle, and milk ranged from
      71.8% to 101.3% with relative standard deviations of less than 8.94%. The online
      SPE and determination were achieved within 15 min, and the monolithic extractor
      was reusable for more than 500 experiments. 

PMID- 25865177
TI  - Clinical findings in 10 children with H275Y influenza A(H1N1)pdm09 virus
      infection.
AB  - BACKGROUND: Little is known about the clinical effectiveness of neuraminidase
      inhibitors against H275Y influenza A(H1N1)pdm09 virus. A cluster of H275Y
      influenza A(H1N1)pdm09 virus with cross-resistance to oseltamivir and peramivir
      was detected among untreated community patients in Hokkaido, Japan, during the
      2013-2014 influenza season. METHODS: This was a retrospective observational
      study. Specimens from nasopharyngeal swabs underwent rapid testing and single
      nucleotide polymorphism identification on real-time polymerase chain reaction. We
      collected clinical data from the H275Y group and a 275H wild-type comparison
      group. All children were given one of four neuraminidase inhibitors. RESULTS:
      Twenty-eight children infected with influenza A(H1N1)pdm09 virus were analyzed.
      Ten viruses had the H275Y substitution, while the other 18 had wild-type 275H.
      Mean fever duration after treatment and after onset was 25.3 h (95%CI: 14.1-36.5)
      and 48.9 h (95%CI: 34.4-63.3) in the H275Y group, respectively, and 26.1 h
      (95%CI: 18.7-33.6) and 46.3 h (95%CI: 35.7-56.8) in the 275H group, respectively.
      In the H275Y group, three patients were treated with oseltamivir, one with
      peramivir, five with zanamivir, and one with laninamivir. All of them had mild
      symptoms and received only outpatient care. Fever duration was 7.5-21.0 h and
      18.0-66.0 h after treatment and after onset, respectively, in the patients
      treated with oseltamivir and peramivir, and 20.5-42.0 h and 42.0-88.0 h,
      respectively, in those treated with zanamivir and laninamivir. CONCLUSION: Fever
      in the H275Y children treated with oseltamivir and peramivir resolved rapidly
      during the 2013-2014 influenza season.

PMID- 25865178
TI  - Versatile plasmid-based expression systems for Gram-negative bacteria--General
      essentials exemplified with the bacterium Ralstonia eutropha H16.
AB  - The Gram-negative bacterium Escherichia coli is currently the most efficient and
      widely used prokaryotic host for recombinant protein and metabolite production.
      However, due to some limitations and to various interesting features of other
      Gram-negative bacteria efficient vector systems applicable to a broad range are
      desired. Basic building blocks for plasmid-based vectors include besides the need
      for a suitable selection marker in the first line a proper replication and
      maintenance system. In addition to these basic requirements, further elements are
      needed for Gram-negative bacteria beyond E. coli, such as Pseudomonas pudita,
      Ralstonia eutropha, Burkholderia glumae or Acinetobacter sp.. Established
      building blocks have to be adapted and new building blocks providing the desired
      functions need to be identified and exploited. This minireview addresses so far
      described and used genetic elements for broad host range replication, efficient
      plasmid maintenance, and conjugative plasmid transfer as well as expression
      elements and protein secretion signals. The industrially important bacterium R.
      eutropha H16 was chosen as a model organism to provide specific data on the
      effectivity and utility of building blocks based on such genetic elements. 

PMID- 25865179
TI  - Diabetes self-management programmes in older adults: a systematic review and meta
      analysis.
AB  - AIM: The evidence for self-management programmes in older adults varies in
      methodological approaches, and disease criteria. Using predetermined
      methodological criteria, we evaluated the effect of diabetes-specific self
      management programme interventions in older adults. METHODS: The EMBASE, MEDLINE
      and Cochrane Central Register of Controlled Trials databases were searched from
      January 1980 to November 2013, as were reference lists from systematic reviews,
      meta-analyses and clinical practice guidelines. A total of 13 trials met the
      selection criteria, which included 4517 older adult participants; 2361
      participants randomized to a diabetes self-management programme and 2156 to usual
      care. RESULTS: The pooled effect on HbA(1c) was a reduction of -2 mmol/mol (
      0.2%; 95% CI -0.3 to -0.1); tailored interventions [-3 mmol/mol (-0.2%; 95% CI 
      0.4 to -0.1)] or programmes with a psychological emphasis [-3 mmol/mol (-0.2; 95%
      CI -0.4 to -0.1)] were most effective. A pooled treatment effect on total
      cholesterol was a 5.81 mg/dl reduction (95% CI -10.33 to -1.29) and non
      significant reductions in systolic and diastolic blood pressure. CONCLUSIONS:
      Diabetes self-management programmes for older adults demonstrate a small
      reduction in HbA(1c), lipids and blood pressure. These findings may be of greater
      clinical relevance when offered in conjunction with other therapies.

PMID- 25865181
TI  - Placebo non-response measure in sequential parallel comparison design studies.
AB  - The Sequential Parallel Comparison Design (SPCD) is one of the novel approaches
      addressing placebo response. The analysis of SPCD data typically classifies
      subjects as 'placebo responders' or 'placebo non-responders'. Most current
      methods employed for analysis of SPCD data utilize only a part of the data
      collected during the trial. A repeated measures model was proposed for analysis
      of continuous outcomes that permitted the inclusion of information from all
      subjects into the treatment effect estimation. We describe here a new approach
      using a weighted repeated measures model that further improves the utilization of
      data collected during the trial, allowing the incorporation of information that
      is relevant to the placebo response, and dealing with the problem of possible
      misclassification of subjects. Our simulations show that when compared to the
      unweighted repeated measures model method, our approach performs as well or,
      under certain conditions, better, in preserving the type I error, achieving
      adequate power and minimizing the mean squared error.

PMID- 25865180
TI  - Multidimensional ultrasound imaging of the wrist: Changes of shape and
      displacement of the median nerve and tendons in carpal tunnel syndrome.
AB  - Dynamics of structures within the carpal tunnel may alter in carpal tunnel
      syndrome (CTS) due to fibrotic changes and increased carpal tunnel pressure.
      Ultrasound can visualize these potential changes, making ultrasound potentially
      an accurate diagnostic tool. To study this, we imaged the carpal tunnel of 113
      patients and 42 controls. CTS severity was classified according to validated
      clinical and nerve conduction study (NCS) classifications. Transversal and
      longitudinal displacement and shape (changes) were calculated for the median
      nerve, tendons and surrounding tissue. To predict diagnostic value binary
      logistic regression modeling was applied. Reduced longitudinal nerve displacement
      (p<= 0.019), increased nerve cross-sectional area (p<= 0.006) and perimeter (p<=
      0.007), and a trend of relatively changed tendon displacements were seen in
      patients. Changes were more convincing when CTS was classified as more severe.
      Binary logistic modeling to diagnose CTS using ultrasound showed a sensitivity of
      70-71% and specificity of 80-84%. In conclusion, CTS patients have altered
      dynamics of structures within the carpal tunnel.

PMID- 25865183
TI  - Shape without Structure: An Intriguing Formation Mechanism in the Solvothermal
      Synthesis of the Phase-Change Material Sb2 Te3.
AB  - We introduce a novel solvothermal synthesis of individual single crystalline Sb2
      Te3 micro- and nanocrystals as a model material for phase-change switching. We
      identified different intermediates along the reaction path to the final Sb2 Te3
      hexagonal platelets (HPs) and discuss their forming mechanism. By means of
      nanodiffraction (ND) in a scanning transmission electron microscope we
      demonstrate that the intermediates follow a hexagonal shape evolution in the
      amorphous state. In situ nanomanipulator measurements reveal electrical phase
      change switching properties of the individual Sb2 Te3 hexagonal platelets. 

PMID- 25865182
TI  - Human epithelial cells exposed to functionalized multiwalled carbon nanotubes:
      interactions and cell surface modifications.
AB  - With the expansion of the production and applications of multiwalled carbon
      nanotubes (MWCNTs) in several industrial and science branches, the potential
      adverse effects on human health have attracted attention. Numerous studies have
      been conducted to evaluate how chemical functionalization may affect MWCNT
      effects; however, controversial data have been reported, showing either increased
      or reduced toxicity. In particular, the impact of carboxylation on MWCNT
      cytotoxicity is far from being completely understood. The aim of this work was
      the evaluation of the modifications induced by carboxylated-MWCNTs (MWCNTs-COOH)
      on cell surface and the study of cell-MWCNT-COOH interactions by means of field
      emission scanning electron microscope (FESEM). Human pulmonary epithelial cells
      (A549) were incubated with MWCNTs-COOH for different exposure times and
      concentrations (10 MUg/mL for 1, 2, 4 h; 5, 10, 20 MUg/mL for 24 h). At short
      incubation time, MWCNTs-COOH were easily observed associated with plasma membrane
      and in contact with microvilli. After 24 h exposure, FESEM analysis revealed that
      MWCNTs-COOH induced evident changes in the cellular surface in comparison to
      control cells: treated cells showed blebs, holes and a depletion of the
      microvilli density in association with structure modifications, such as widening
      and/or lengthening. In particular, an increase of cells showing holes and
      microvilli structure alterations was observed at 20 MUg/mL concentration. FESEM
      analysis showed nanotube agglomerates, of different sizes, entering into the cell
      with two different mechanisms: inward bending of the membrane followed by
      nanotube sinking, and nanotube internalization directly through holes. The
      observed morphological microvilli modifications, induced by MWCNTs-COOH, could
      affect epithelial functions, such as the control of surfactant production and
      secretion, leading to pathological conditions, such as alveolar proteinosis. More
      detailed studies will be, however, necessary to examine in depth the effects
      induced by MWCNTs-COOH and, in particular, the timing of the MWCNT-COOH-cell
      interaction. 

PMID- 25865184
TI  - Livestock-associated MRSA: innocent or serious health threat?

PMID- 25865185
TI  - Metabolic flexibility and morphological plasticity in mycobacteria.

PMID- 25865186
TI  - T4 bacteriophage-mediated inhibition of adsorption and replication of human
      adenovirus in vitro.
AB  - AIM: The objective of this study was to evaluate the effects of T4 phage on
      adsorption and replication of human adenovirus (HAdV). MATERIALS & METHODS:
      Experiments were performed on cell lines A549 and HEK-293. Intracellular HAdV
      virions were released and titrated by Reed-Muench method. RESULTS: T4
      significantly (p < 0.05) inhibited both the adsorption of HAdV and viral
      replication in a dose-dependent manner. Mean reductions in HAdV titer were within
      the range 0.634-2.12 and 0.238-1.88 log10 TCID50/ml for HAdV adsorption and
      replication, respectively. CONCLUSION: T4 phage can inhibit infections by HAdV-5
      of target cells. Our results suggest that T4 might be considered a novel agent
      against HAdV and possibly other pathogenic viruses. Potential antiviral effects
      of other phages should also be investigated.

PMID- 25865187
TI  - Detection of Mycobacterium ulcerans subsp. shinshuense DNA from a water channel
      in familial Buruli ulcer cases in Japan.
AB  - AIM: To determine if Mycobacterium ulcerans subsp. shinshuense is present in the
      common living environment in a case of familial concurrent occurrence of Buruli
      ulcer in Japan. MATERIALS & METHODS: Environmental samples were collected
      primarily from a water channel in the patient's residence. A combination of whole
      genome amplification, touchdown PCR and DNA sequencing was used to detect M.
      ulcerans subsp. shinshuense DNA. RESULTS: M. ulcerans subsp. shinshuense DNA was
      detected in a crayfish sampled in July, but not in other samples including a
      crayfish sampled in October. CONCLUSION: These findings support an association
      between contaminated aquatic environments and Buruli ulcer in Japan. The data
      also suggest dynamic seasonal appearance of the pathogen in the environment may
      contribute to the seasonal variation of Buruli ulcer occurrence in Japan.

PMID- 25865188
TI  - Host-pathogen interactions in Vibrio vulnificus: responses of monocytes and
      vascular endothelial cells to live bacteria.
AB  - AIM: To demonstrate that Vibrio vulnificus, a sepsis-related aquatic pathogen,
      can provoke a strong pro-inflammatory reaction in blood-associated target cells.
      MATERIALS & METHODS: We selected two strains of the two main phylogenetic
      lineages, two human cell lines, monocytes and vascular endothelial cells and
      designed an in vitro infection model simulating early septicemia. RESULTS: Both
      strains caused a strong cell-specific pro-inflammatory response and produced a
      high degree of cell damage that ended with death by lysis (endothelial cells) or
      apoptosis/lysis (monocytes). The interaction with endothelial cells was stronger
      than expected and significantly different for both lineages. CONCLUSION: The
      early interaction with endothelial cells could have a direct role in sepsis and
      could explain, at least partially, the differences in pathogenicity between both
      lineages.

PMID- 25865189
TI  - Involvement of cholesterol in Campylobacter jejuni cytolethal distending toxin
      induced pathogenesis.
AB  - AIM: The aim of this study was to investigate whether cholesterol plays a pivotal
      role in cytolethal distending toxin (CDT) mediated pathogenic effects in hosts.
      MATERIALS & METHODS: The molecular mechanisms underlying cholesterol sequestering
      conferred resistance to CDT-induced DNA double-strand breaks (DSBs) and cell
      cycle arrest were investigated. Histopathological analysis was conducted for
      evaluating CDT-induced intestinal inflammation in mouse. RESULTS: CDT actions
      were attenuated by treatment of cells with methyl-beta-cyclodextrin (MbetaCD).
      Severe intestinal inflammation induced by CDT treatment was observed in high
      cholesterol diet-fed mice, but not in normal diet-fed mice, indicating that
      cholesterol is essential for CDT intoxication. CONCLUSION: Our findings
      demonstrate a molecular link between Campylobacter jejuni CDT and cholesterol,
      which is crucial to facilitate CDT-induced pathogenesis in hosts.

PMID- 25865190
TI  - Measles virus hemagglutinin epitopes are potential hotspots for crossreactions
      with immunodeficiency-related proteins.
AB  - AIMS: Measles virus (MV) infection induces a protective immunity that is
      accompanied by a transient pathologic suppression of the immune system. This
      immunologic paradox remains unexplained in spite of the numerous hypotheses that
      have been advanced (i.e., cytokine production, soluble immunosuppressive factor,
      cell cycle block, signaling lymphocyte activation molecule receptor and MV
      infection of dendritic cells, among others). METHODS: Searching for molecular
      link(s) between MV infection and host immunodeficiency, this study used the
      Immune Epitope DataBase to analyze the peptide sharing between the antigenic MV
      hemagglutinin (H) protein and human proteins associated with immunodeficiency.
      RESULTS: It was found that the majority of MVH derived epitopes share several
      exact pentapeptide sequences with numerous human proteins involved in immune
      functions and immunodeficiency, such as B- and T-cell antigens, and complement
      components. CONCLUSION: The data suggest that crossreactivity might contribute to
      our understanding of the link between MV immunogenicity and MV-induced
      immunosuppression, and highlight peptides unique to MV as a basis for developing
      effective and safe anti-MV vaccines.

PMID- 25865191
TI  - Is there interaction between gut microbial profile and cardiovascular risk in
      chronic kidney disease patients?
AB  - AIM: To evaluate the gut microbial profile in chronic kidney disease (CKD)
      patients and evaluate the possible relationship with inflammation and
      cardiovascular risk. PATIENTS & METHODS: Markers inflammation plasma and
      bacterial community profile (denaturing gradient gel electrophoresis) were
      analyzed. RESULTS: The average number of bands was not different in healthy
      individuals and CKD patients. The number of bands was negatively associated with
      plasma levels of VCAM-1 in patients. Flavobacteriaceae bacterium and Listeria
      monocytogenes were found in patients and Lachnospiraceae bacterium and
      Butyrivibrio crossotus in healthy individuals. CONCLUSION: Although CKD patients
      did not present altered gut microbial profile, the sequencing of bands suggested
      a different microbiota between groups. The result suggests a possible
      relationship between gut microbiota and cardiovascular risk in CKD patients.

PMID- 25865192
TI  - Molecular diagnosis of bovine tuberculosis in bovine and human samples:
      implications for zoonosis.
AB  - AIM: To develop emerging diagnostic technique for bovine tuberculosis and to
      identify its potential risk factors. MATERIALS & METHODS: Bacterial genomic DNA
      was isolated from bovine milk and human sputum samples and subjected to PCR using
      specific primer pairs. PCR results were validated using bacteriological cultures.
      RESULTS: PCR amplification of the targeted DNA fragment of Mycobacterium bovis
      was successful in 12.33% (37/300) of the bovine samples. Interestingly, 500-bp
      DNA fragment was also amplified in 6.67% (6/90) of the sputum indicating the
      possibility of zoonotic transmission. Rearing of livestock in household,
      unpasteurized milk consumption and smoking were identified as potential risk
      factors. CONCLUSION: Results of the study may add value to bovine tuberculosis
      eradication campaigns to achieve the One Health initiative.

PMID- 25865193
TI  - Strategies for detecting rickettsiae and diagnosing rickettsial diseases.
AB  - Rickettsial diseases and scrub typhus constitute a group of the oldest known
      vector-borne diseases. The cosmopolitan distribution of the vectors that transmit
      rickettsiae and orientiae leads to a worldwide prevalence of these diseases.
      Despite their significant historical status, detection and diagnosis of these
      diseases are still evolving today. Serological methods remain among the most
      prevalent techniques used for the detection/diagnosis of rickettsial diseases and
      scrub typhus. Molecular techniques have been instrumental in increasing the
      sensitivity/specificity of diagnosis, identifying new Rickettsia and Orientia
      species and have enhanced epidemiological capabilities when used in combination
      with serological methods. In this review, we discuss these techniques and their
      associated pros and cons.

PMID- 25865195
TI  - Cell-autonomous responses in Listeria monocytogenes infection.
AB  - Listeria monocytogenes is a facultative intracellular bacterium causing
      listeriosis, a food-borne infection with a high mortality rate. The mechanisms
      and the role of cells and tissular components in generating protective adaptive
      immune responses are well studied, and cell biological studies provide a detailed
      understanding of the processes targeted by the bacterial products. Much less is
      known of the cellular responses activated to limit infection in individual cells
      when confronted with stress or infection. Eukaryotic cellular responses depend on
      multitiered homeostatic systems that ensure maintenance of proteostatis,
      organellar integrity, function and turnover, and overall cellular viability ('the
      cell-autonomous response'). Here, we review the cell-autonomous responses induced
      during extracellular and intracellular L. monocytogenes growth and discuss their
      contribution to limiting infection.

PMID- 25865196
TI  - Evolutionary insight from whole-genome sequencing of Pseudomonas aeruginosa from
      cystic fibrosis patients.
AB  - The opportunistic pathogen Pseudomonas aeruginosa causes chronic airway
      infections in patients with cystic fibrosis (CF), and it is directly associated
      with the morbidity and mortality connected with this disease. The ability of P.
      aeruginosa to establish chronic infections in CF patients is suggested to be due
      to the large genetic repertoire of P. aeruginosa and its ability to genetically
      adapt to the host environment. Here, we review the recent work that has applied
      whole-genome sequencing to understand P. aeruginosa population genomics, within
      host microevolution and diversity, mutational mechanisms, genetic adaptation and
      transmission events. Finally, we summarize the advances in relation to medical
      applications and laboratory evolution experiments.

PMID- 25865197
TI  - Actinomycosis: a frequently forgotten disease.
AB  - Actinomycosis is a rare subacute or chronic, endogenous infection mainly by
      Actinomyces species, showing low virulence through fimbriae and biofilms.
      Cervicofacial, thoracic, abdominal, pelvic and sometimes cerebral, laryngeal,
      urinary and other regions can be affected. Actinomycosis mimics other diseases,
      often malignancy. Disease risk in immunocompromised subjects needs clarification.
      Diagnosis is often delayed and 'sulfur granules' are helpful but nonspecific.
      Culture requires immediate specimen transport and prolonged anaerobic incubation.
      Imaging, histology, cytology, matrix-assisted laser desorption ionization time-of
      flight mass spectrometry and molecular methods improve the diagnosis.
      Actinomycetes are beta-lactam susceptible, occasionally resistant. Treatment
      includes surgery and/or long-term parenteral then oral antibiotics, but some 1-4
      week regimens or oral therapy alone were curative. For prophylaxis, oral hygiene
      and regular intrauterine device replacement are important.

PMID- 25865198
TI  - Coxsackievirus B3 replication and pathogenesis.
AB  - Viruses such as coxsackievirus B3 (CVB3) are entirely host cell-dependent
      parasites. Indeed, they must cleverly exploit various compartments of host cells
      to complete their life cycle, and consequently launch disease. Evolution has
      equipped this pico-rna-virus, CVB3, to use different strategies, including CVB3
      induced direct damage to host cells followed by a host inflammatory response to
      CVB3 infection, and cell death to super-additively promote target organ tissue
      injury, and dysfunction. In this update, the patho-stratagems of CVB3 are
      explored from molecular, and systems-level approaches. In summarizing recent
      developments in this field, we focus particularly on mechanisms by which CVB3 can
      harness different host cell processes including kinases, host cell-killing and
      cell-eating machineries, matrix metalloproteinases and miRNAs to promote disease.

PMID- 25865194
TI  - Host immunity to Cryptococcus neoformans.
AB  - Cryptococcosis is caused by the fungal genus Cryptococcus. Cryptococcosis,
      predominantly meningoencephalitis, emerged with the HIV pandemic, primarily
      afflicting HIV-infected patients with profound T-cell deficiency. Where in use,
      combination antiretroviral therapy has markedly reduced the incidence of and risk
      for disease, but cryptococcosis continues to afflict those without access to
      therapy, particularly in sub-Saharan Africa and Asia. However, cryptococcosis
      also occurs in solid organ transplant recipients and patients with other
      immunodeficiencies as well as those with no known immunodeficiency. This article
      reviews innate and adaptive immune responses to C. neoformans, with an emphasis
      on recent studies on the role of B cells, natural IgM and Fc gamma receptor
      polymorphisms in resistance to cryptococcosis.

PMID- 25865199
TI  - Genotyping Streptococcus pneumoniae.
AB  - Streptococcus pneumoniae is a potentially deadly human pathogen associated with
      high morbidity, mortality and global economic burden. The universally used
      bacterial genotyping methods are multilocus sequence typing and pulsed field gel
      electrophoresis. However, another highly discriminatory, rapid and less expensive
      genotyping technique, multilocus variable number of tandem repeat analysis
      (MLVA), has been developed. Unfortunately, no universal MLVA protocol exists, and
      some MLVA protocols do not amplify certain loci for all pneumococcal serotypes,
      leaving genotyping profiles incomplete. A number of other genotyping or
      characterization methods have been developed and will be discussed. This review
      examines the various protocols for genotyping S. pneumoniae and highlights the
      current direction technology and research is heading to understand this
      bacterium.

PMID- 25865200
TI  - Adoptive T-cell therapy in the treatment of viral and opportunistic fungal
      infections.
AB  - Viral infections and opportunistic fungal pathogens represent a major menace for
      immunocompromised patients. Despite the availability of antifungal and antiviral
      drugs, mortality in these patients remains high, underlining the need of novel
      therapeutic options based on completely different strategies. This review
      describes the potential of several T-cell-based therapeutic approaches in the
      prophylaxis and treatment of infectious diseases with a particular focus on
      persistent viral infections and opportunistic fungal infections, as these mostly
      affect immunocompromised patients.

PMID- 25865201
TI  - A unifying theory of tonsillitis, intratonsillar abscess and peritonsillar
      abscess.
AB  - We review existing models of the pathogenesis of peritonsillar abscess (PTA) and
      intra-tonsillar abscess (ITA) and present a novel pathophysiologic model based
      upon observed histopathology in 2 ITAs and 10 PTAs and acute tonsillitis cases.
      ITA is rare, and prevailing models are only able to account for a minority of
      cases. The tonsillar lymphatic ultrastucture and the rapid nature of
      intratonsillar lymphatic transit, offer the framework for a unifying model of the
      development and progression of tonsillitis, PTA and ITA. 

PMID- 25865202
TI  - Conscious Neuromodulation of the Bladder before Clinical Use.

PMID- 25865204
TI  - Study of eating attitudes and behaviours in junior college students in Mumbai,
      India.
AB  - BACKGROUND: Eating disorders have been described as possible 'culture-bound
      syndromes', with roots in Western cultural values and conflicts. They may, in
      fact, be more prevalent within various non-Western cultural groups than
      previously recognised, as Western values become more widely accepted. Cross
      cultural experiences suggest that cultural change itself may be associated with
      increased vulnerability to eating disorders, especially when Western values about
      physical aesthetics are involved. OBJECTIVE: to assess the eating attitudes and
      behaviours among adolescents in the urban ethnic city, Mumbai, a survey was
      conducted amongst 451 college students. METHOD: the study, based in four junior
      colleges, comprised 451 subjects who completed a semi-structured questionnaire, a
      26-item Eating Attitudes Test (EAT-26) and the Personal Assessment Inventory
      (IPAT). RESULTS: the results revealed faulty eating habits in 13.3% of the
      subjects. A statistically significant proportion perceived them-selves to have
      problems with eating, substance use, dieting and exercise practices, resorting to
      extreme measures to achieve weight loss. A high rate of faulty eating habits was
      observed in males. Higher scores on depression and suicidal ideation were
      reported in the population with faulty eating habits. CONCLUSION: a significant
      percentage of college-going populations in urban settings probably have faulty
      eating habits.

PMID- 25865205
TI  - Could a healthy ego identity serve as a protective factor against suicidal
      tendencies? A pilot study.
AB  - OBJECTIVE: The study investigated the interrelationship between adolescent ego
      identity, suicidal tendencies, gender and race in a sample of South African
      Indian and Black secondary school students. METHOD: The Ego Identity Scale (EIS)
      and the Multi-attitude Suicide Tendency Scale (MAST) were administered to 63
      learners between the ages of 15 and 20 years. RESULTS: Pearson correlations and t
      tests were used to analyse the data. The results indicate that higher scores on
      the EIS correlate with lower suicidal tendencies for this sample. In addition,
      higher scores were recorded by females on the Attraction to Death subscale and by
      Black males on the Attraction to Death, Repulsion by Life and Repulsion by Death
      subscales of the MAST. CONCLUSION: The authors conclude that ego identity
      achievement is likely to serve as a protective factor against suicidal
      tendencies.

PMID- 25865206
TI  - Utility of the Koppitz norms for the Bender Gestalt Test performance of a group
      of Sesotho-speaking children.
AB  - OBJECTIVE: This study investigated the utility of the Koppitz administration,
      scoring and norms for the Bender Gestalt Test (BGT) as a neurocognitive screening
      instrument for Sesotho-speaking children. METHOD: The BGT protocols of 671
      Sesotho-speaking children between the ages of seven and nine were reviewed. Data
      pertaining to socioeconomic status were also gathered for 360 of the
      participants. The BGT performance of the Sesotho sample was compared to that of
      the original Koppitz norm group. Furthermore, the two groups were compared with
      regard to their respective age-related rates of improvement in BGT performance.
      The effects of gender and socioeconomic status on the BGT performance of the
      Sesotho group were also investigated. RESULTS: The Sesotho-speaking group
      incurred a significantly higher number of errors, compared to the Koppitz norm
      group. Moreover, the Sesotho group exhibited no age-related improvement in their
      BGT performance. Socioeconomic status showed no effect on the group's BGT
      performance, while age only showed a significant effect within the nine-year-old
      group. CONCLUSIONS: The BGT exhibits limited utility as a screening instrument
      for neurocognitive impairment amongst Sesotho-speaking children. Limitations of
      the current study are highlighted and suggestions are made regarding future
      directions for research.

PMID- 25865207
TI  - Media messaging: a synthesis of lessons from the literature to inform HIV
      prevention amongst young people.
AB  - Based on a review of literature, we provide a number of challenges and lessons to
      inform HIV-prevention media messaging initiatives for the youth. When designing
      initiatives, it is imperative that the unique needs of the youth are taken into
      account, although the youth should not be seen as a homogenous group. The
      evaluation of initiatives is also important and external evaluators and
      implementers should work together and draw on methodological pluralism to produce
      the most useful evaluations. For media initiatives to be successful, all
      stakeholders need to support the intervention. A key challenge is working with
      communities who may be divided over approaches to HIV prevention. Young people
      should not only be the 'target' of messaging initiatives but should play a
      central role in their design and implementation. Exposure to media messaging is
      not a proxy for behaviour change. Initiatives should be based on explicit
      theories of the complex relationship between messaging and behaviour change. It
      is important for media messaging to engage with how structures constrain sexual
      choices. Messaging is most successful when it uses a multi-media approach and
      when it is combined with interpersonal communication. This type of pedagogy is
      dialogical and allows for engagement with the youth, challenging the view of the
      youth as passive recipients of messages. 

PMID- 25865208
TI  - Working with a child's envy in the transference.
AB  - In literature, envy has long been written of as one of the seven cardinal sins.
      In biblical mythology, envy as a consequence of vanity can be understood to be
      the reason for archangel Lucifer's fall from a state of heavenly grace and
      unionship. Freud was the first psychoanalytic theorist to introduce the idea of
      envy, albeit through his controversial concept of penis envy. Karl Abrahams and
      Melanie Klein later placed envy at the crucial developing stages of the
      relationship between primary caregiver and infant. Klein boldly identified envy
      as a primary constitutional emotion. However, the presence and difficulties of
      envy in clinical work remain largely underreported, more so in work with
      children. This paper asks whether an attachment base can be secure if envy is
      dominant. The analysis of a nine-year-old girl ('Kirsten') and her envious
      transference with her therapist will be examined, to explore the relationship
      between envy and attachment security. While contemporary research focuses on
      developing attachment theory in relation to specific psychiatric conditions, this
      paper will discuss affect as the binding link or disruptive force between self
      and object representations, that then determine attachment security. 

PMID- 25865211
TI  - Education and intellectual disability in South Africa.

PMID- 25865209
TI  - Psychodynamic aspects of suicidal risk in adolescence: two case studies.
AB  - Two cases of attempted suicide by adolescents, following the separation from an
      idealised first sexual partner, are presented to illustrate psychodynamic issues
      often overlooked in clinical assessment. Absent fathers and father figures and
      other psychodynamic issues are explored. 

PMID- 25865212
TI  - The child psychiatric nurse specialist in South Africa.

PMID- 25865213
TI  - Geometric stability and reaction activity of Pt clusters adsorbed graphene
      substrates for catalytic CO oxidation.
AB  - The geometric stabilities, electronic structures and catalytic properties of
      tetrahedral Pt4 clusters anchored on graphene substrates are investigated using
      the first-principles methods. It is found that the small Pt4 clusters adsorbed on
      pristine graphene substrates easily interconvert between structural isomers by
      the small energy barriers, while the structural interconversion of Pt4 clusters
      on the defective graphene and oxygen-doped graphene (O-graphene) have the large
      energy barriers. Compared to other graphene substrates, the Pt4 clusters
      supported on the O-graphene substrate (Pt4/O-graphene) have the least geometrical
      distortion and the high symmetry of the Pt4 cluster can enhance the sensitivity
      of reactive gases. Moreover, the sequential reactions of CO oxidation on Pt4/O
      graphene are investigated for comparison. Compared with the coadsorption reaction
      of CO and O2 molecules, the dissociative adsorption of O2 as a starting step has
      a small energy barrier (0.07 eV) and is followed through the Eley-Rideal reaction
      with an energy barrier of 0.42 eV (CO + Oads -> CO2). The results provide
      valuable guidance for fabricating graphene-based catalysts as anode materials,
      and explore the microscopic mechanism of the CO oxidation reaction on atomic
      scale catalysts. 

PMID- 25865214
TI  - Allogeneic stem cell transplantation in multiple myeloma: immunotherapy and new
      drugs.
AB  - INTRODUCTION: Autologous (auto) stem cell transplantation (SCT) and the
      development of new drugs have improved the survival of multiple myeloma (MM)
      patients. By contrast, though potentially curative, the use of allogeneic (allo)
      SCT is controversial. AREAS COVERED: A review has been conducted to examine the
      current evidence for the use of allo-SCT in MM. We have examined novel cell
      therapies that may be exploited to induce myeloma-specific immune responses
      including the new promising frontier of chimeric antigen receptor (CAR)-T and 
      natural killer (NK) cells. EXPERT OPINION: One of the major controversies facing
      researchers in exploring the allo approach is the remarkable recent treatment
      improvement observed with second- and third-generation proteasome inhibitors and
      immunomodulatory drugs, monoclonal antibodies and deacetylase inhibitors. Despite
      these great advances, the disease remains to be incurable and allo-SCT may still
      play a role in the cure of MM. We think that allo-SCT conserves a role in MM and
      its curative potential in high-risk patients should be explored in the setting of
      control clinical trials. Novel cell therapies such as CAR technologies may open
      new avenues of research toward a potential cure. Data from currently ongoing
      prospective studies will be helpful to clarify pending clinical questions.

PMID- 25865216
TI  - Replacing home visits with telephone calls to support parents implementing a
      sleep management intervention: findings from a pilot study and implications for
      future research.
AB  - BACKGROUND: Resource constraints may inhibit the provision of appropriate
      interventions for children with neurodisabilities presenting with behavioural
      sleep problems. Telephone calls (TC), as opposed to home visits (HV), may be a
      more resource efficient means of supporting these families. OBJECTIVE: To conduct
      a preliminary investigation exploring the feasibility and acceptability of
      replacing HV with TC to support parents implementing sleep management strategies
      and to gather evidence to inform the design and methods of a full trial. METHODS:
      Parents referred to a sleep management intervention routinely delivered by a
      community paediatric team were alternately allocated to receive implementation
      support via HV (n = 7) or TC (n = 8). Activity logs recorded the frequency,
      duration and mode of support. Parents and practitioners were interviewed about
      their experiences of receiving/delivering the intervention. RESULTS: Intervention
      drop-out was low, the frequency, number of contacts and intervention duration
      appeared comparable. Parents allocated TC received less contact time. Parents
      valued implementation support irrespective of delivery mode and practitioners
      reported that despite initial reservations, implementation support via TC
      appeared to work well. CONCLUSIONS: TC appears an acceptable and convenient mode
      of delivering sleep support, valued by both parents and practitioners. We
      recommend a full-scale trial to investigate effectiveness.

PMID- 25865215
TI  - Techniques and applications of in vivo diffusion imaging of articular cartilage.
AB  - Early in the process of osteoarthritis (OA) the composition (water, proteoglycan
      [PG], and collagen) and structure of articular cartilage is altered leading to
      changes in its mechanical properties. A technique that can assess the composition
      and structure of the cartilage in vivo can provide insight in the mechanical
      integrity of articular cartilage and become a powerful tool for the early
      diagnosis of OA. Diffusion tensor imaging (DTI) has been proposed as a biomarker
      for cartilage composition and structure. DTI is sensitive to the PG content
      through the mean diffusivity and to the collagen architecture through the
      fractional anisotropy. However, the acquisition of DTI of articular cartilage in
      vivo is challenging due to the short T2 of articular cartilage (~40 ms at 3
      Tesla) and the high resolution needed (0.5-0.7 mm in plane) to depict the
      cartilage anatomy. We describe the pulse sequences used for in vivo DTI of
      articular cartilage and discus general strategies for protocol optimization. We
      provide a comprehensive review of measurements of DTI of articular cartilage from
      ex vivo validation experiments to its recent clinical applications.

PMID- 25865217
TI  - Au-Edged CuZnSe2 Heterostructured Nanosheets with Enhanced Electrochemical
      Performance.
AB  - Two-dimensional (2D) nanomaterials and heterostructured nanocrystals (NCs) are
      two hot topics in current nanoresearch. However, reports on heterostructured NCs
      with 2D features are still rare. In this work, we demonstrate a one-pot colloidal
      chemistry route for synthesizing Au-CuZnSe2 heterostructures with spherical Au
      domains attached to the edge of a sheet of CuZnSe2 . This protocol involves the
      preferential formation of Au clusters and the seeded growth of CuZnSe2 sheets
      because of the lattice matching of CuSe with Au. As an example to demonstrate the
      importance of such heterostructures, the electrochemical performance of Au
      CuZnSe2 heterostructured nanosheets is compared with that of heterostructured
      nanorods, Au NCs, and CuZnSe2 NCs. The heterostructured nanosheets exhibit the
      best electrochemical activity. 

PMID- 25865219
TI  - Temperature-dependent studies of [(CH3)2NH2][Fe(III)M(II)(HCOO)6] frameworks
      (M(II) = Fe and Mg): structural, magnetic, dielectric and phonon properties.
AB  - Novel heterometallic formate [(CH3)2NH2][Fe(III)Mg(II)(HCOO)6] (DMFeMg) was
      prepared and characterized by single crystal X-ray diffraction, DSC, dielectric,
      magnetic susceptibility, Raman and IR methods. We also report thermal, Raman and
      IR studies of the known compound [(CH3)2NH2][Fe(III)Fe(II)(HCOO)6] (DMFeFe).
      DMFeMg crystallizes in the niccolite structure (P3[combining macron]1c space
      group). In contrast to the known DMFeFe, [(CH3)2NH2][Fe(III)Mn(II)(HCOO)6]
      (DMFeMn) and [(CH3)2NH2][Fe(III)Co(II)(HCOO)6] (DMFeCo) formates, the metal ions
      in DMFeMg are distributed statistically over the two available octahedral sites.
      Temperature-dependent studies show that whereas DMFeFe exhibits an order-disorder
      phase transition at 151.8 K upon cooling, freezing-in of re-orientational motions
      of DMA(+) cations does not lead to any structural phase transition in DMFeMg. We
      discuss the origin of this difference. The low-temperature studies also show that
      DMFeMg orders magnetically at TC = 13.5(5) K and the shape of M(T) measured in
      the field-cooling regime suggests ferromagnetic character of the ordering. 

PMID- 25865218
TI  - Effect of background noise on neuronal coding of interaural level difference cues
      in rat inferior colliculus.
AB  - Humans can accurately localize sounds even in unfavourable signal-to-noise
      conditions. To investigate the neural mechanisms underlying this, we studied the
      effect of background wide-band noise on neural sensitivity to variations in
      interaural level difference (ILD), the predominant cue for sound localization in
      azimuth for high-frequency sounds, at the characteristic frequency of cells in
      rat inferior colliculus (IC). Binaural noise at high levels generally resulted in
      suppression of responses (55.8%), but at lower levels resulted in enhancement
      (34.8%) as well as suppression (30.3%). When recording conditions permitted, we
      then examined if any binaural noise effects were related to selective noise
      effects at each of the two ears, which we interpreted in light of well-known
      differences in input type (excitation and inhibition) from each ear shaping
      particular forms of ILD sensitivity in the IC. At high signal-to-noise ratios
      (SNR), in most ILD functions (41%), the effect of background noise appeared to be
      due to effects on inputs from both ears, while for a large percentage (35.8%)
      appeared to be accounted for by effects on excitatory input. However, as SNR
      decreased, change in excitation became the dominant contributor to the change due
      to binaural background noise (63.6%). These novel findings shed light on the IC
      neural mechanisms for sound localization in the presence of continuous background
      noise. They also suggest that some effects of background noise on encoding of
      sound location reported to be emergent in upstream auditory areas can also be
      observed at the level of the midbrain. 

PMID- 25865220
TI  - [Pilot study on stress and resilience in families with premature newborns].
AB  - INTRODUCTION: Prematurity is associated with severe clinical conditions, long
      hospital stays, and uncertainty about patient outcomes. These circumstances lead
      to a stressful situation that may affect family functioning. The aim of this
      study was to study risk and protection factors affecting family functioning in
      preterm as compared to healthy term infants. POPULATION AND METHODS: Preterm
      infants with and without pathological conditions (n=40) were recruited at 24
      months post-conception age, together with a control group of healthy term newborn
      infants (n=31). Parents or usual caregivers responded to the Inventory of Family
      Protection Factors and Parental Stress scales. The results were compared using
      the Student t test, unidirectional analysis of variance and the Tukey test.
      RESULTS: Parents of the control group attained higher scores than those of the
      preterm group for all the items studied; however, parents of preterm infants with
      pathological conditions perceived significantly less family resilience and more
      stress related to the upbringing of their child. CONCLUSIONS: Prematurity itself
      is a risk factor for family dysfunction because it causes an elevated degree of
      parental stress and difficulties in the development of protection factors such as
      resilience.

PMID- 25865221
TI  - [Development deficit risks in the late premature newborn: Evaluation at 48 months
      using the Ages & Stages Questionnaires(r)].
AB  - INTRODUCTION: Lack of specific monitoring protocols hinders the knowledge of the
      impact of late prematurity on delayed psychomotor development. The objective of
      this study is to evaluate this at 48 months and compare it with those born at
      term. POPULATION AND METHODS: A retrospective cohort study was conducted on 90
      late preterm (PT) and 89 term (AT) healthy children at 48 months, assessed by the
      Ages & Stages Questionnaires(r) (ASQ-3). Continuous variables described using
      mean and standard deviation compared with the t Student t test for independent
      samples. The categorical variables were described as frequencies and proportions,
      compared with the Chi-square test of independence. A cut-off was determined for
      the total score of ASQ-3 able to discriminate the risk of developmental deficit
      by a ROC analysis. A step-wise logistic regression model identified the
      associated risk factors. RESULTS: The mean scores for each domain and overall ASQ
      3 score showed no differences between groups. However, when analyzing the
      probability density for the ASQ-3 total score of <=251 points, 15 PT (16.6%) and
      4 AT (4.5%) showed risk of psychomotor deficits, and late prematurity and lack of
      breastfeeding were significantly associated factors. CONCLUSIONS: There is an
      increased prevalence of risk of development deficit in the PT, which justifies
      considering this population at risk and establishing effective monitoring
      programs. It should be further investigated whether this risk corresponds to the
      entire population, or if there are biological factors or perinatal history that
      makes them more vulnerable.

PMID- 25865222
TI  - Maintaining immunosuppressive treatment after early allograft nephrectomy does
      not reduce the risk of anti-HLA allosensitization.

PMID- 25865223
TI  - Should Oscillometric Blood Pressure Monitors Be Used in Patients With Atrial
      Fibrillation?

PMID- 25865224
TI  - Prognostic value of monocyte and neutrophils to lymphocytes ratio in patients
      with metastatic soft tissue sarcoma.
AB  - Metastatic soft tissue sarcomas (STS) represent enormous challenges to improve
      the low survival rate, which is almost the same as past 2 decades ago. Prognosis
      of cancer patients are based not only on tumor-related factors but also on host
      related factors, particularly systemic inflammatory response. We evaluated the
      association among possible risk factors and survival for metastatic STS by
      reviewed a single-institution nearly 50-year experience. We found that both
      monocyte ratio and NLR ratio were significant prognostic predictors for OS and
      PFS of metastatic STS. And patients with monocyte ratio or NLR ratio > 1 should
      be screened out as candidates for more intensive or aggressive multimodality
      treatments and more aggressive follow-up. For this reason, this result could
      serve as a basis for future prospective study. 

PMID- 25865225
TI  - Prognostic and predictive values of long non-coding RNA LINC00472 in breast
      cancer.
AB  - LINC00472 is a novel long intergenic non-coding RNA. We evaluated LINC00472
      expression in breast tumor samples using RT-qPCR, performed a meta-analysis of
      over 20 microarray datasets from the Gene Expression Omnibus (GEO) database, and
      investigated the effect of LINC00472 expression on cell proliferation and
      migration in breast cancer cells transfected with a LINC00472-expressing vector.
      Our qPCR results showed that high LINC00472 expression was associated with less
      aggressive breast tumors and more favorable disease outcomes. Patients with high
      expression of LINC00472 had significantly reduced risk of relapse and death
      compared to those with low expression. Patients with high LINC00472 expression
      also had better responses to adjuvant chemo- or hormonal therapy than did
      patients with low expression. Results of meta-analysis on multiple studies from
      the GEO database were in agreement with the findings of our study. High LINC00472
      was also associated with favorable molecular subtypes, Luminal A or normal-like
      tumors. Cell culture experiments showed that up-regulation of LINC00472
      expression could suppress breast cancer cell proliferation and migration.
      Collectively, our clinical and in vitro studies suggest that LINC00472 is a tumor
      suppressor in breast cancer. Evaluating this long non-coding RNA in breast tumors
      may have prognostic and predictive value in the clinical management of breast
      cancer. 

PMID- 25865227
TI  - Novel agents that downregulate EGFR, HER2, and HER3 in parallel.
AB  - EGFR, HER2, and HER3 contribute to the initiation and progression of human
      cancers, and are therapeutic targets for monoclonal antibodies and tyrosine
      kinase inhibitors. An important source of resistance to these agents arises from
      functional redundancy among EGFR, HER2, and HER3. EGFR family members contain
      conserved extracellular structures that are stabilized by disulfide bonds.
      Compounds that disrupt extracellular disulfide bonds could inactivate EGFR, HER2,
      and HER3 in unison. Here we describe the identification of compounds that kill
      breast cancer cells that overexpress EGFR or HER2. Cell death parallels
      downregulation of EGFR, HER2, and HER3. These compounds disrupt disulfide bonds
      and are termed Disulfide Bond Disrupting Agents (DDAs). DDA RBF3 exhibits
      anticancer efficacy in vivo at 40 mg/kg without evidence of toxicity. DDAs may
      complement existing EGFR-, HER2-, and HER3-targeted agents that function through
      alternate mechanisms of action, and combination regimens with these existing
      drugs may overcome therapeutic resistance. 

PMID- 25865226
TI  - Silencing of R-Spondin1 increases radiosensitivity of glioma cells.
AB  - Although radiation therapy is the most effective postoperative adjuvant
      treatment, it does not substantially improve the long-term outcomes of glioma
      patients because of the characteristic radioresistance of glioma. We found that R
      Spondin1 (Rspo1) expression was elevated in high-grade gliomas and was associated
      with worse overall survival and disease-free survival. Rspo1 expression was also
      associated with reduced survival rates in glioma patients after treatment with
      radiotherapy and temozolomide (RT-TMZ). Importantly, Rspo1 was dramatically
      upregulated after radiation treatment in patients with glioma. Rspo1 silencing by
      shRNA potentiated glioma cell death upon radiation treatment. In a xenograft nude
      mouse model, combining radiation and silencing of Rspo1 potentiated tumor growth
      inhibition. Thus, combining radiotherapy with silencing of Rspo1 is a potential
      therapeutic approach. 

PMID- 25865229
TI  - Investigating the surface state of graphene quantum dots.
AB  - A universal route to GQDs is developed based on "solution phase-based scissor"
      methods. The PL centers of the GQDs are systematically studied and are proved to
      be the surface state. This is related to the hybridization structure of the edge
      groups and the connected partial graphene core. Through experiment and analysis,
      we have preliminarily proved that the efficient edge groups for green emission
      are mainly carboxyl, carbonyl and amide. This is indicated by the following three
      factors: firstly, the PL of GQDs is enhanced by UV exposure, during which partial
      -OH groups are converted into carboxyl groups; secondly, the PL properties of
      GQDs can be further improved by one-step solvothermal treatment, in which partial
      carboxyl groups are converted to amide groups and the surface state of the GQDs
      is enhanced; thirdly, reduced m-GQDs possess more -OH groups compared with
      reduced GQDs, resulting in more blue PL centers (the carboxyl, carbonyl and amide
      based green centers are converted to -OH-based blue centers). The present work
      highlights a very important direction for the understanding of the PL mechanism
      of GQDs and other related carbon-based materials. 

PMID- 25865228
TI  - Autoimmune response to PARP and BRCA1/BRCA2 in cancer.
AB  - PURPOSE: To determine the role of autoantibodies to PARP1 and BRCA1/BRCA2 which
      were involved in the synthetic lethal interaction in cancer. METHODS: Enzyme
      Linked Immunosorbent Assay (ELISA) was used to detect autoantibodies to PARP1 and
      BRCA1/BRCA2 in 618 serum samples including 131 from breast cancer, 94 from lung
      cancer, 34 from ovarian cancer, 107 from prostate cancer, 76 from liver cancer,
      41 from pancreatic cancer and 135 from normal individuals. The positive sera with
      ELISA were confirmed by Western blot. Immunohistochemistry was used to examine
      the expression of PARP1 and BRCA1/BRCA2 in breast cancer. RESULTS: Autoantibody
      frequency to PARP1, BRCA1, and BRCA2 in cancer varied from 0% to 50%. When the
      sera from cancer patients were tested for the presence of autoantibodies to PARP1
      and BRCA1/BRCA2, the autoantibody responses slightly decreased and the positive
      autoantibody reactions varied from 0% to 50.0%. This was significantly higher
      autoantibody responses to PARP1 and BRCA1/BRCA2 (especially to PARP1 and BRCA1)
      in ovarian cancer and breast cancer compared to normal control sera (P < 0.001
      and P < 0.01). Immunohistochemistry indicated that Pathology Grade at diagnosis
      to PARP1 expression in breast cancer was different (P < 0.05). CONCLUSIONS:
      Different cancers have different profiles of autoantibodies. The autoantibodies
      to proteins involving the synthetic lethal interactions would be novel
      serological biomarker in some selective cancers.

PMID- 25865230
TI  - Open chest core needle biopsy of left ventricle in the evaluation of suspected
      focal myocardial inflammation.

PMID- 25865231
TI  - Salinity and dissolved organic carbon both affect copper toxicity in mussel
      larvae: Copper speciation or competition cannot explain everything.
AB  - Predicting copper (Cu) toxicity in marine and estuarine environments is
      challenging because of the influence of anions on Cu speciation, competition
      between Cu(2+) and other cations at the biotic ligand and the effect of salinity
      on the physiology of the organism. In the present study the combined effect of
      salinity and dissolved organic carbon (DOC) on Cu toxicity to larvae of Mytilus
      galloprovincialis was assessed. Two statistical models were developed and used to
      elucidate the relationship between Cu toxicity, salinity, and DOC. All models
      based on dissolved Cu indicate a decrease in Cu toxicity with increasing DOC
      concentrations, which can partly be explained by complexation of Cu(2+) ions with
      DOC. These models also indicate an increase in Cu toxicity (modeled with
      dissolved Cu or Cu(2+) activity) with increasing salinity, suggesting a salinity
      induced alteration in the physiology of the mussel larvae. When based on Cu body
      burdens, neither of the models indicates an effect of salinity or DOC. This shows
      that the Cu body burden is a more constant predictor of Cu toxicity, regardless
      of the water chemistry influencing Cu speciation or competition and possible
      physiological alterations or changes in Cu speciation or competition.

PMID- 25865232
TI  - Human immunoglobulin (KIOVIG(r)/GAMMAGARD LIQUID(r)) for immunodeficiency and
      autoimmune diseases: an observational cohort study.
AB  - AIM: To document the therapeutic efficacy and safety of Human Normal
      Immunoglobulin 10% Liquid (KIOVIG((r))/GAMMAGARD LIQUID((r)) [IVIG 10%]) under
      clinical routine conditions. PATIENTS & METHODS: Subjects received IVIG 10%
      according to the prescribing information and were followed for 6 +/- 1 weeks to
      12 +/- 2 months depending on indication. Efficacy, adverse events, infusion rates
      and duration and dose were recorded. RESULTS: Overall efficacy of IVIG 10% was
      rated as good or very good by the investigator in 81.8% of subjects; overall
      tolerability was good or very good in 87.5%. One serious adverse drug reaction
      (ADR) occurred (urticaria); no severe ADRs occurred. CONCLUSION: In this
      observational study, the efficacy and safety of IVIG 10% in routine clinical
      practice was similar to that previously reported in clinical studies.

PMID- 25865233
TI  - The dramatic effect of dapsone on cutaneous bullous and pustular rheumatoid
      vasculitis on the sole.

PMID- 25865235
TI  - The impact of endoscopic sinus surgery on total direct healthcare costs among
      patients with chronic rhinosinusitis.
AB  - BACKGROUND: This study investigates how endoscopic sinus surgery (ESS) impacts
      total direct healthcare costs, medication usage, and frequency of imaging among
      patients with chronic rhinosinusitis (CRS). METHODS: Data were obtained from the
      MarketScan(r) Commercial Claims and Encounters databases (Truven Health
      Analytics); patients who underwent ESS for CRS in 2008 were identified.
      Healthcare costs, days of antibiotic and oral steroid usage, and number of
      computed tomography (CT) and magnetic resonance imaging (MRI) studies were
      collected for 12 months prior to and 36 months after surgery and compared in 1
      year intervals. RESULTS: A total of 8963 surgical patients were included. Median
      total direct costs fell from $4750 at preoperative baseline (95% confidence
      interval [CI], $4661 to $4838) to $4212 by year 3 after surgery (95% CI, $4078 to
      $4346). Disease-specific costs related to conditions commonly associated with CRS
      asthma, allergy, depression, and headache-all decreased in the years after
      surgery; the reduction was significant for all conditions but asthma. Mean days
      of antibiotic usage per year decreased from 28.2 days before surgery to 15.9 days
      by year 3 after surgery, p value <0.001. Days of oral corticosteroid usage
      remained stable at just over 7 days. Mean number of imaging studies fell from an
      average of 1.6 in the year before surgery to 0.2 by year 3 after surgery, p value
      <0.001. CONCLUSION: Among patients who underwent ESS for CRS, total direct
      healthcare costs, antibiotic usage, and number of imaging studies decreased after
      surgery, and remained below preoperative levels throughout all 3 years of follow
      up. Oral corticosteroid usage remained stable.

PMID- 25865236
TI  - Balloon aortic valvuloplasty as a treatment option in the era of transcatheter
      aortic valve implantation.
AB  - Aortic valve stenosis is the commonest encountered valvular pathology and a
      frequent cause of morbidity and mortality in cases of severe stenosis. Definitive
      treatment has traditionally been offered in the form of surgical aortic valve
      replacement in patients with an acceptable surgical risk and more recently with
      the less invasive transcatheter aortic valve implantation (TAVI) in those where
      surgery is not a viable option. Prior to the introduction of TAVI, inoperable
      patients were treated medically and where appropriate with balloon aortic
      valvuloplasty, a procedure which although effective only provided short-term
      relief and was associated with high complication rates especially during its
      infancy. Here we discuss whether balloon aortic valvuloplasty continues to have a
      role in contemporary clinical practice in an era where significant advances have
      been achieved in the fields of surgical aortic valve replacement, TAVI and
      postoperative care. 

PMID- 25865237
TI  - EphB4 forward signalling regulates lymphatic valve development.
AB  - Bidirectional signalling is regarded as a notable hallmark of the Eph-ephrin
      signalling system: Eph-dependent forward signalling in Eph-expressing cells and
      ephrin-dependent reverse signalling in Ephrin-expressing cells. The notion of
      ephrin-dependent reverse signalling derives from genetic experiments utilizing
      mice carrying mutations in the intracellular region of ephrinBs. Here we show
      that EphB4-dependent forward signalling regulates lymphatic valve development, a
      process previously thought to be regulated by ephrinB2-dependent reverse
      signalling. We develop antibodies that selectively target EphB4 and ephrinB2. We
      find that mice bearing genetically altered cytoplasmic region of ephrinB2 have
      significantly altered EphB4-dependent forward signalling. Selective inhibition of
      EphB4 using a functional blocking antibody results in defective lymphatic valve
      development. Furthermore, a chemical genetic approach is used to unequivocally
      show that the kinase activity of EphB4 is essential for lymphatic valve
      development. 

PMID- 25865238
TI  - Clozapine-induced myocarditis, a widely overlooked adverse reaction.
AB  - OBJECTIVE: We review the published cases of clozapine-induced myocarditis and
      describe reasons for the higher incidence in Australia (>1%) than elsewhere
      (<0.1%). METHOD: Medline was searched to September 2014 using 'clozapine' as the
      sole term. RESULTS: A total of around 250 cases of clozapine-induced myocarditis
      have been published. Fever among patients commencing clozapine has been reported
      internationally, and very few of these cases were investigated for myocarditis.
      The time to onset of fever is consistent with its being part of a prodrome of
      undiagnosed myocarditis, and the risk factors are similar to those for
      myocarditis. In more severe cases, clozapine is discontinued, avoiding fatalities
      which may occur with myocarditis. Furthermore, cases of sudden death and
      respiratory illness may well have been undiagnosed myocarditis. The diagnosis of
      myocarditis is confounded by the non-specific nature of the signs and symptoms,
      and it depends on appropriate investigations being conducted at the time of
      myocardial involvement or, for fatal cases, the affected area of the myocardium
      being sampled for histology. CONCLUSION: It is likely that the incidence of
      myocarditis is around 3%. Implementation of monitoring procedures will increase
      case ascertainment and result in more patients benefiting from this valuable
      medication.

PMID- 25865239
TI  - Aortic fibroelastoma: detailed preoperative analysis with 3D echocardiography.

PMID- 25865241
TI  - Reprint of: Impact of alcohols on the formation and stability of protein
      stabilized nanoemulsions.
AB  - Nanoemulsions are increasingly being used for encapsulation, protection, and
      delivery of bioactive lipids, however, their formation from natural emulsifiers
      is still challenging. We investigated the impact of alcohol on the formation and
      stability of protein-stabilized oil-in-water nanoemulsions prepared by high
      pressure homogenization. The influence of different alcohols (ethanol, 1
      propanol, and 1-butanol) at various concentrations (0-25% w/w) on the formation
      and stability of emulsions stabilized by sodium caseinate, whey protein isolate,
      and fish gelatin was investigated. The mean particle diameter decreased with
      increasing alcohol concentrations from 0 to 10%w/w, but extensive droplet
      aggregation occurred at higher levels. This phenomenon was attributed to enhanced
      protein-protein interactions between the adsorbed emulsifier molecules in the
      presence of alcohol leading to droplet flocculation. The smallest droplets (d<100
      nm) were obtained when 10%w/w 1-butanol was added to sodium caseinate-stabilized
      nanoemulsions, but relatively small droplets (d<150 nm) could also be obtained in
      the presence of a food-grade alcohol (ethanol). This study demonstrated that
      alcohol addition might be a useful tool for producing protein-stabilized
      nanoemulsions suitable for use as delivery systems of lipophilic bioactive
      agents.

PMID- 25865242
TI  - Anti-cancer effect of N-(3,5-bis(trifluoromethyl)phenyl)-5-chloro-2,3
      dihydronaphtho[1,2-b]furan-2-carboxamide, a novel synthetic compound.
AB  - Naphthofuran compounds have been known to regulate HNF 4alpha which is associated
      with proliferation, progression and metastasis of HCC. In this study, we
      investigated whether N-(3,5-bis(trifluoromethyl)phenyl)-5-chloro-2,3
      dihydronaphtho[1,2-b]furan-2-carboxamide (NHDC), a novel synthetic naphthofuran
      compound inhibits liver tumor growth through activation of HNF 4alpha. Treatment
      with different concentrations (1-10.8 uM) of NHDC for various periods (0-72 h)
      inhibited liver cancer cells (HepG2, Hep3B) growth as well as colony formation
      followed by induction of apoptosis in a concentration dependent manner. NHDC also
      induced expression of the apoptosis regulating genes as well as inhibiting the
      action of STAT3. These inhibitory effects were associated with enhancement of
      expression and DNA binding activity of HNF 4alpha. In vivo study confirmed that
      liver tumor growth was prevented with NHDC (5 mg/kg), and its effect was also
      related with inhibition of STAT3 pathway through enhancement of expression and
      DNA binding activity of HNF 4alpha. Moreover, siRNA of HNF 4alpha abolished NHDC
      induced cell growth inhibition as well as DNA binding activity and
      phosphorylation of STAT3. Pull down assay docking prediction analysis proved that
      NHDC directly binds to hydrophobic fatty acid ligand binding site of HNF 4alpha.
      A novel naphthofuran compound, NHDC inhibited liver tumor growth by inactivating
      of STAT3 through direct biding to HNF 4alpha.

PMID- 25865243
TI  - Co-infection of Nucleospora cyclopteri (Microsporidia) and Kudoa islandica
      (Myxozoa) in farmed lumpfish, Cyclopterus lumpus L., in Norway: a case report.
AB  - This study describes a co-infection of Kudoa islandica (Myxozoa) and Nucleospora
      cyclopteri (Microsporida) in farmed lumpfish, Cyclopterus lumpus L., in Norway.
      Several other parasites (Cryptocotyle sp., protozoan ciliates and Gyrodactylus
      sp.) were also found in gills. In June 2013, the mortality in a farmed lumpfish
      population increased to 65%. Lumpfish showed erratic swimming behaviour and loss
      of weight. At necropsy, nodules in the kidney were the only visible lesions.
      Histologically, all fish showed severe changes with gill inflammation and
      necrosis in the spleen, kidney and liver. Haemorrhages and necrosis were observed
      in some hearts. Intracellular microsporidians associated with the lesions were
      detected in most organs using histological examination and Calcofluor White.
      Kudoa spores were diagnosed in the skeletal muscle, but no inflammatory response
      was associated with the presence of the plasmodia. Comparison of 18S ribosomal
      DNA sequences showed 100% similarity to Kudoa islandica and Nucleospora
      cyclopteri. Kudoa islandica and N. cyclopteri have previously been described
      associated with lesions in wild lumpfish in Iceland. In the present case, N.
      cyclopteri is believed to be the main cause of systemic pathology. This is the
      first description of K. islandica and N. cyclopteri causing pathology in farmed
      lumpfish in Norway. 

PMID- 25865244
TI  - Crystal Structure of the Peroxo-diiron(III) Intermediate of Deoxyhypusine
      Hydroxylase, an Oxygenase Involved in Hypusination.
AB  - Deoxyhypusine hydroxylase (DOHH) is a non-heme diiron enzyme involved in the
      posttranslational modification of a critical lysine residue of eukaryotic
      translation initiation factor 5A (eIF-5A) to yield the unusual amino acid residue
      hypusine. This modification is essential for the role of eIF-5A in translation
      and in nuclear export of a group of specific mRNAs. The diiron center of human
      DOHH (hDOHH) forms a peroxo-diiron(III) intermediate (hDOHHperoxo) when its
      reduced form reacts with O2. hDOHHperoxo has a lifetime exceeding that of the
      peroxo intermediates of other diiron enzymes by several orders of magnitude. Here
      we report the 1.7-A crystal structures of hDOHHperoxo and a complex with
      glycerol. The structure of hDOHHperoxo reveals the presence of a MU-1,2-peroxo
      diiron(III) species at the active site. Augmented by UV/Vis and Mossbauer
      spectroscopic studies, the crystal structures offer explanations for the extreme
      longevity of hDOHHperoxo and illustrate how the enzyme specifically recognizes
      its only substrate, deoxyhypusine-eIF-5A. 

PMID- 25865245
TI  - Tubulation by amphiphysin requires concentration-dependent switching from wedging
      to scaffolding.
AB  - BAR proteins are involved in a variety of membrane remodeling events but how they
      can mold membranes into different shapes remains poorly understood. Using
      electron paramagnetic resonance, we find that vesicle binding of the N-BAR
      protein amphiphysin is predominantly mediated by the shallow insertion of
      amphipathic N-terminal helices. In contrast, the interaction with tubes involves
      deeply inserted N-terminal helices together with the concave surface of the BAR
      domain, which acts as a scaffold. Combined with the observed concentration
      dependence of tubulation and BAR domain scaffolding, the data indicate that
      initial membrane deformations and vesicle binding are mediated by insertion of
      amphipathic helical wedges, while tubulation requires high protein densities at
      which oligomeric BAR domain scaffolds form. In addition, we identify a pocket of
      residues on the concave surface of the BAR domain that insert deeply into tube
      membrane. Interestingly, this pocket harbors a number of disease mutants in the
      homologous amphiphysin 2. 

PMID- 25865247
TI  - CyToStruct: Augmenting the Network Visualization of Cytoscape with the Power of
      Molecular Viewers.
AB  - It can be informative to view biological data, e.g., protein-protein interactions
      within a large complex, in a network representation coupled with three
      dimensional structural visualizations of individual molecular entities.
      CyToStruct, introduced here, provides a transparent interface between the
      Cytoscape platform for network analysis and molecular viewers, including PyMOL,
      UCSF Chimera, VMD, and Jmol. CyToStruct launches and passes scripts to molecular
      viewers from the network's edges and nodes. We provide demonstrations to analyze
      interactions among subunits in large protein/RNA/DNA complexes, and similarities
      among proteins. CyToStruct enriches the network tools of Cytoscape by adding a
      layer of structural analysis, offering all capabilities implemented in molecular
      viewers. CyToStruct is available at
      https://bitbucket.org/sergeyn/cytostruct/wiki/Home and in the Cytoscape App
      Store. Given the coordinates of a molecular complex, our web server
      (http://trachel-srv.cs.haifa.ac.il/rachel/ppi/) automatically generates all files
      needed to visualize the complex as a Cytoscape network with CyToStruct bridging
      to PyMOL, UCSF Chimera, VMD, and Jmol. 

PMID- 25865246
TI  - FlaF Is a beta-Sandwich Protein that Anchors the Archaellum in the Archaeal Cell
      Envelope by Binding the S-Layer Protein.
AB  - Archaea employ the archaellum, a type IV pilus-like nanomachine, for swimming
      motility. In the crenarchaeon Sulfolobus acidocaldarius, the archaellum consists
      of seven proteins: FlaB/X/G/F/H/I/J. FlaF is conserved and essential for
      archaellum assembly but no FlaF structures exist. Here, we truncated the FlaF N
      terminus and solved 1.5-A and 1.65-A resolution crystal structures of this
      monotopic membrane protein. Structures revealed an N-terminal alpha-helix and an
      eight-strand beta-sandwich, immunoglobulin-like fold with striking similarity to
      S-layer proteins. Crystal structures, X-ray scattering, and mutational analyses
      suggest dimer assembly is needed for in vivo function. The sole cell envelope
      component of S. acidocaldarius is a paracrystalline S-layer, and FlaF
      specifically bound to S-layer protein, suggesting that its interaction domain is
      located in the pseudoperiplasm with its N-terminal helix in the membrane. From
      these data, FlaF may act as the previously unknown archaellum stator protein that
      anchors the rotating archaellum to the archaeal cell envelope. 

PMID- 25865248
TI  - Structural Basis for the Catalytic Mechanism of DncV, Bacterial Homolog of Cyclic
      GMP-AMP Synthase.
AB  - Cyclic dinucleotides (CDNs) play key roles as second messengers and signaling
      molecules in bacteria and metazoans. The newly identified dinucleotide cyclase in
      Vibrio cholerae (DncV) produces three different CDNs containing two 3'-5'
      phosphodiester bonds, and its predominant product is cyclic GMP-AMP, whereas
      mammalian cyclic GMP-AMP synthase (cGAS) produces only cyclic GMP-AMP containing
      mixed 2'-5' phosphodiester bonds. We report the crystal structures of V. cholerae
      and Escherichia coli DncV in complex with various nucleotides in the pre-reaction
      states. The high-resolution structures revealed that DncV preferably recognizes
      ATP and GTP as acceptor and donor nucleotides, respectively, in the first
      nucleotidyl transfer reaction. Considering the recently reported intermediate
      structures, our pre-reaction state structures provide the precise mechanism of 3'
      5' linked cyclic AMP-GMP production in bacteria. A comparison with cGAS in the
      pre-reaction states suggests that the orientation of the acceptor nucleotide
      primarily determines the distinct linkage specificities between DncV and cGAS. 

PMID- 25865249
TI  - Evaluation of influenza vaccine effectiveness and description of circulating
      strains in outpatient settings in South Africa, 2014.
AB  - The effectiveness of the trivalent seasonal influenza vaccine during the 2014
      season in South Africa was assessed using a test-negative case-control study
      design including 472 cases and 362 controls. Influenza A(H3N2) was the dominant
      strain circulating. The overall vaccine effectiveness estimate, adjusted for age
      and underlying conditions, was 43.1% (95% CI: -26.8-74.5). 2014 H3N2 viruses from
      South Africa were mainly in sublineage 3C.3 with accumulation of amino acid
      changes that differentiate them from the vaccine strain in 3C.1. 

PMID- 25865250
TI  - Protein "amyloid-like" networks at the phospholipid membrane formed by 4-hydroxy
      2-nonenal-modified mitochondrial creatine kinase.
AB  - 4-Hydroxy-2-nonenal (4-HNE) is a reactive aldehyde and a lipid peroxidation
      product formed in biological tissues under physiological and pathological
      conditions. Its concentration increases with oxidative stress and induces
      deleterious modifications of proteins and membranes. Mitochondrial and cytosolic
      isoforms of creatine kinase were previously shown to be affected by 4-HNE. In the
      present study, we analyzed the effect of 4-HNE on mitochondrial creatine kinase,
      an abundant protein from the mitochondrial intermembrane space with a key role in
      mitochondrial physiology. We show that this effect is double: 4-HNE induces a
      step-wise loss of creatine kinase activity together with a fast protein
      aggregation. Protein-membrane interaction is affected and amyloid-like networks
      formed on the biomimetic membrane. These fibrils may disturb mitochondrial
      organisation both at the membrane and in the inter membrane space. 

PMID- 25865252
TI  - Highly chemoselective and versatile method for direct conversion of carboxylic
      acids to ketones utilizing zinc ate complexes.
AB  - Various carboxylic acids were directly transformed into the corresponding ketones
      by utilizing organozinc ate complexes, which provide high chemoselectivity
      without any overreaction to the undesired tertiary carbinol, owing to formation
      of a stable tetrahedral zincioketal intermediate. This method offers good overall
      atom/step/pot economy and operational simplicity. 

PMID- 25865253
TI  - Hydration and Hydrogen Bond Network of Water during the Coil-to-Globule
      Transition in Poly(N-isopropylacrylamide) Aqueous Solution at Cloud Point
      Temperature.
AB  - Aqueous solutions of poly(N-isopropylacrylamide), P-NIPAAm, exhibit a noticeable
      temperature responsive change in molecular conformation at a cloud point
      temperature (Tcp). As the temperature rises above Tcp, the extended coil-like P
      NIPAAm structure changes into a swollen globule-like conformation as hydration
      levels decrease and hydrophobic interactions increase. Though water plays an
      important role in this coil-to-globule transition of P-NIPAAm, the behavior of
      water molecules and the associated hydrogen-bond (HB) network of the surrounding
      bulk water are still veiled in uncertainty. In this study, we elucidate changes
      in the hydration state and the dynamical structure of the water HB network of P
      NIPAAm aqueous solutions during the coil-to-globule transition by analyzing the
      complex dielectric constant in the terahertz region (0.25-12 THz), where bulk
      water reorientations and intermolecular vibrations of water can be selectively
      probed. The structural properties of the water HB network were examined in terms
      of the population of the non-HB water molecules (not directly engaged in the HB
      network or hydrated to P-NIPAAm) and the tetrahedral coordination of the water
      molecules engaged in the HB network. We found the hydration number below Tcp
      (~10) was decreased to approximately 6.5 as temperature increased, in line with
      previous studies. The HB network of bulk water becomes more structured as the
      coil-to-globule phase transition takes place, via decreases in non-HB water and
      reduction in the orderliness of the tetrahedral HB architecture. Together these
      results indicate that the coil-to-globule transition is associated with a shift
      to hydrophobic-dominated interactions that drive thermoresponsive structural
      changes in the surrounding water molecules. 

PMID- 25865251
TI  - Immunology of IgG4-related disease.
AB  - Immunoglobulin G4-related disease (IgG4-RD) is a fibroinflammatory condition that
      derives its name from the characteristic finding of abundant IgG4(+) plasma cells
      in affected tissues, as well as the presence of elevated serum IgG4
      concentrations in many patients. In contrast to fibrotic disorders, such as
      systemic sclerosis or idiopathic pulmonary fibrosis in which the tissues fibrosis
      has remained largely intractable to treatment, many IgG4-RD patients appear to
      have a condition in which the collagen deposition is reversible. The mechanisms
      underlying this peculiar feature remain unknown, but the remarkable efficacy of B
      cell depletion in these patients supports an important pathogenic role of B
      cell/T cell collaboration. In particular, aberrant T helper type 2
      (Th2)/regulatory T cells sustained by putative autoreactive B cells have been
      proposed to drive collagen deposition through the production of profibrotic
      cytokines, but definitive demonstrations of this hypothesis are lacking. Indeed,
      a number of unsolved questions need to be addressed in order to fully understand
      the pathogenesis of IgG4-RD. These include the identification of an antigenic
      trigger(s), the implications (if any) of IgG4 antibodies for pathophysiology and
      the precise immunological mechanisms leading to fibrosis. Recent investigations
      have also raised the possibility that innate immunity might precede adaptive
      immunity, thus further complicating the pathological scenario. Here, we aim to
      review the most recent insights on the immunology of IgG4-RD, focusing on the
      relative contribution of innate and adaptive immune responses to the full
      pathological phenotype of this fibrotic condition. Clinical, histological and
      therapeutic features are also addressed. 

PMID- 25865254
TI  - Oxygen demand of perfused heart preparations: how electromechanical function and
      inadequate oxygenation affect physiology and optical measurements.
AB  - NEW FINDINGS: What is the topic of this review? This review discusses how the
      function and electrophysiology of isolated perfused hearts are affected by
      oxygenation and energy utilization. The impact of oxygenation on fluorescence
      measurements in perfused hearts is also discussed. What advances does it
      highlight? Recent studies have illuminated the inherent differences in
      electromechanical function, energy utilization rate and oxygen requirements
      between the primary types of excised heart preparations. A summary and analysis
      of how these variables affect experimental results are necessary to elevate the
      physiological relevance of these approaches in order to advance the field of
      whole-heart research. The ex vivo perfused heart recreates important aspects of
      in vivo conditions to provide insight into whole-organ function. In this review
      we discuss multiple types of ex vivo heart preparations, explain how closely each
      mimic in vivo function, and discuss how changes in electromechanical function and
      inadequate oxygenation of ex vivo perfused hearts may affect measurements of
      physiology. Hearts that perform physiological work have high oxygen demand and
      are likely to experience hypoxia when perfused with a crystalloid perfusate.
      Adequate myocardial oxygenation is critically important for obtaining
      physiologically relevant measurements, so when designing experiments the type of
      ex vivo preparation and the capacity of perfusate to deliver oxygen must be
      carefully considered. When workload is low, such as during interventions that
      inhibit contraction, oxygen demand is also low, which could dramatically alter a
      physiological response to experimental variables. Changes in oxygenation also
      alter the optical properties of cardiac tissue, an effect that may influence
      optical signals measured from both endogenous and exogenous fluorophores. Careful
      consideration of oxygen supply, working condition, and wavelengths used to
      acquire optical signals is critical for obtaining physiologically relevant
      measurements during ex vivo perfused heart studies.

PMID- 25865255
TI  - The rat ErbB2 tyrosine kinase receptor produced in plants is immunogenic in mice
      and confers protective immunity against ErbB2(+) mammary cancer.
AB  - The rat ErbB2 (rErbB2) protein is a 185-kDa glycoprotein belonging to the
      epidermal growth factor-related proteins (ErbB) of receptor tyrosine kinases.
      Overexpression and mutations of ErbB proteins lead to several malignancies
      including breast, lung, pancreatic, bladder and ovary carcinomas. ErbB2 is
      immunogenic and is an ideal candidate for cancer immunotherapy. We investigated
      the possibility of expressing the extracellular (EC) domain of rErbB2 (653 amino
      acids, aa) in Nicotiana benthamiana plants, testing the influence of the 23 aa
      transmembrane (TM) sequence on protein accumulation. Synthetic variants of the
      rErbB2 gene portion encoding the EC domain, optimized with a human codon usage
      and either linked to the full TM domain (rErbB2_TM, 676 aa), to a portion of it
      (rErbB2-pTM, 662 aa), or deprived of it (rErbB2_noTM, 653 aa) were cloned in the
      pEAQ-HT expression vector as 6X His tag fusions. All rErbB2 variants (72-74.5
      kDa) were transiently expressed, but the TM was detrimental for rErbB2 EC
      accumulation. rERbB2_noTM was the most expressed protein; it was solubilized and
      purified with Nickel affinity resin. When crude soluble extracts expressing
      rErbB2_noTM were administered to BALB/c mice, specific rErbB2 immune responses
      were triggered. A potent antitumour activity was induced when vaccinated mice
      were challenged with syngeneic transplantable ErbB2(+) mammary carcinoma cells.
      To our knowledge, this is the first report of expression of rErbB2 in plants and
      of its efficacy in inducing a protective antitumour immune response, opening
      interesting perspectives for further immunological testing. 

PMID- 25865256
TI  - Exosomal sorting of the viral oncoprotein LMP1 is restrained by TRAF2 association
      at signalling endosomes.
AB  - The Epstein-Barr virus (EBV)-encoded oncoprotein latent membrane protein 1 (LMP1)
      constitutively activates nuclear factor kappaB (NFkappaB) from intracellular
      membranes to promote cell growth and survival. LMP1 associates with CD63 in
      intracellular membranes and is released via exosomes. Whether tumour necrosis
      factor (TNF) receptor-associated factors (TRAFs) mediate LMP1 NFkappaB signalling
      from endosomes and modulate exosomal sorting is unknown. In this article, we show
      that LMP1-TRAF2 signalling complexes accumulate at endosomes in a palmitoylation
      dependent manner, thereby driving LMP1-dependent oncogenicity. Palmitoylation is
      a reversible post-translational modification and is considered to function as a
      membrane anchor for proteins. Mutagenesis studies showed that LMP1-TRAF2
      trafficking to endosomes is dependent on one single cysteine residue (C78), a
      known palmitoylation site of LMP1. Notably, growth assays in soft agar revealed
      that oncogenic properties of the palmitoylation-deficient LMP1 mutant C78A were
      diminished compared to wild-type LMP1. Since LMP1 recruitment of TRAF2 and
      downstream NFkappaB signalling were not affected by a disturbance in
      palmitoylation, the specific localization of LMP1 at endosomal membranes appears
      crucial for its transforming potential. The importance of palmitoylation for
      trafficking to and signalling from endosomal membranes was not restricted to
      LMP1, as similar observations were made for the cellular oncoproteins Src and
      Fyn. Despite abundant LMP1-TRAF2 association at endosomal membranes TRAF2 could
      not be detected in exosomes by Western blotting or proteomics. Interestingly,
      point mutations that prevented TRAF binding strongly promoted the sorting and
      release of LMP1 via exosomes. These observations reveal that LMP1-TRAF2 complexes
      at endosomes support oncogenic NFkappaB activation and suggest that LMP1
      dissociates from the activated signalling complexes upon sorting into
      intraluminal vesicles. We propose that "signalling endosomes" in EBV-infected
      tumour cells can fuse with the plasma membrane, explaining LMP1 release via
      exosomes. 

PMID- 25865257
TI  - Importance of sudden cardiac death risk stratification in hypertrophic
      cardiomyopathy.

PMID- 25865258
TI  - Combining BRAF(V) (600E) inhibition with modulators of the mitochondrial
      bioenergy metabolism to overcome drug resistance in metastatic melanoma.

PMID- 25865259
TI  - Brief Report: Factors Released by Megakaryocytes Thrombin Cleave Osteopontin to
      Negatively Regulate Hematopoietic Stem Cells.
AB  - Factor V (FV) and factor X (FX) activate and complex to form prothrombinase which
      subsequently cleaves prothrombin (PT), converting it to active thrombin. Thrombin
      cleaved osteopontin (tcOPN) contains a cryptic binding site for alpha4 beta1 and
      alpha9 beta1 integrins. We have previously shown that hematopoietic stem cells
      (HSC) bind to tcOPN via this site resulting in a decrease in their proliferation
      and differentiation. Therefore, tcOPN and the factors required for its generation
      are important components of the HSC niche. Herein we show mature megakaryocytes
      (MM, >=8N) contain FV, FX, and PT mRNA and protein. Furthermore, we show 8N, 16N,
      32N, and 64N MM all release the required factors to enable thrombin cleavage of
      OPN. Importantly, mice devoid of the myeloproliferative leukemia protein (Mpl), c
      Mpl(-/-) mice, contain only approximately 10% of normal megakaryocyte numbers,
      showed significantly reduced FX and tcOPN protein levels in endosteal bone marrow
      (BM). In addition, WT hematopoietic progenitors and HSC showed reduced homing to
      the BM of c-Mpl(-/-) mice. This is the first report identifying MM as a key
      cellular component in the production of tcOPN in situ, allowing the BM
      microenvironment to self regulate HSC biology via tcOPN.

PMID- 25865260
TI  - Enhanced healing of mitomycin C-treated healing-impaired wounds in rats with PRP
      containing fragmin/protamine microparticles (PRP&F/P MPs).
AB  - PURPOSE: The purpose of this study was to evaluate the accelerating effects of
      platelet-rich plasma-containing (PRP&) fragmin/protamine microparticles (F/P MPs)
      for repairing mitomycin C-treated healing-impaired wounds. Staining with terminal
      deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL-staining)
      showed that apoptosis of dermal fibroblast cells (DFCs) and epidermal
      keratinocyte cells (EKCs) were significantly induced in the skin of the mitomycin
      C-treated rats. METHOD: Full-thickness skin defects were made on the back of rats
      and mitomycin C was applied on the wounds to prepare a healing-impaired wound.
      After washing out the mitomycin C, saline (control), F/P MPs alone, PRP alone,
      and PRP&F/P MPs were injected around the wounds. The rats were later euthanised
      and histological sections of the wounds were then prepared at indicated time
      periods after the treatment. RESULTS AND CONCLUSION: These results indicated the
      numbers of large, medium, and small capillary lumens 7 days after injection of
      PRP&F/P MPs were significantly higher than those after injection of PRP or F/P
      MPs alone. Furthermore, epithelium and granulation tissue formations were
      significantly stimulated in the healing-impaired wounds treated with PRP&F/P MPs
      3, 7 and 14 days after injection of PRP&F/P MPs.

PMID- 25865261
TI  - Urban park-related risks for Giardia spp. infection in dogs.
AB  - Giardia spp. is a common gastrointestinal (GI) parasite of multiple host species,
      including dogs and humans, with the potential for zoonotic transmission. The risk
      of GI parasitism in dogs (including Giardia spp.) may increase with park use in
      urban areas. This study aimed to (1) determine whether park attendance is a risk
      factor for Giardia spp. infection in dogs and (2) characterize the behavioural
      and demographic risk factors for Giardia spp. infection in park-attending and non
      park-attending dogs. From August to September 2012, a total of 1293 dog owners
      completed a survey and 860 corresponding dog faecal samples were collected. Dog
      faeces were screened for Giardia spp. using a direct immunofluorescence assay and
      associations assessed among behaviours, demographics, and Giardia spp. infection.
      Main results included off-leash and swimming frequencies within parks as
      significantly positively associated with Giardia spp. infection in dogs. Dog
      owner age was negatively associated with off-leash and swimming frequencies in
      parks. The results suggest some recreational behaviours in parks and certain
      demographics are risk factors for parasitism in pet dogs. 

PMID- 25865262
TI  - Three-dimensional laser flow measurements of a patient-specific fontan physiology
      with mechanical circulatory assistance.
AB  - Mechanical assistance of the Fontan circulation is hypothesized to enhance
      ventricular preload and improve cardiac output; however, little is known about
      the fluid dynamics. This study is the first to investigate the three-dimensional
      flow conditions of a blood pump in an anatomic Fontan. Laser measurements were
      conducted having an axial flow impeller in the inferior vena cava. Experiments
      were performed for a physiologic cardiac output, pulmonary arterial flows, and
      pump speeds of 1000-4000 rpm. The impeller had a modest effect on the flow
      conditions entering the total cavopulmonary connection at low pump speeds, but a
      substantial impact on the velocity at higher speeds. The higher speeds of the
      pump disrupted the recirculation region in the center of the anastomosis, which
      could be advantageous for washout purposes. No retrograde velocities in the
      superior vena cava were measured. These findings indicate that mechanical
      assistance is a viable therapeutic option for patients having dysfunctional
      single ventricle physiology.

PMID- 25865263
TI  - Detection of circulating immune complexes of human IgA and beta 2 glycoprotein I
      in patients with antiphospholipid syndrome symptomatology.
AB  - BACKGROUND: Patients with antiphospholipid syndrome (APS) have a hypercoagulable
      condition associated with the presence of antiphospholipid autoantibodies (aPL).
      Consensus antibodies for diagnosis are lupus anticoagulant, anti-beta2
      glycoprotein I (B2GPI) and anticardiolipin (IgG or IgM). Circulating
      immunocomplexes (CIC) of B2GPI associated with IgM or IgG were reported. Isolated
      IgA aB2GPI antibodies have achieved high diagnostic value although specific CIC
      of B2GPI bounded to IgA (B2A-CIC) has still not been described. CIC detection
      assays are mainly based on interaction with complement and are not appropriate to
      detect B2A-CIC because IgA does not fix complement using the classical pathway.
      PATIENTS AND METHODS: Sera from healthy blood donors (N= 247) and from patients
      with thrombosis background and isolate positive for IgA aB2GPI (N = 68) were
      studied in a case-control study. Two methods were applied, these being a capture
      ELISA to quantify specific B2A-CIC and quantification of total IgA anti-B2GPI
      after dissociating CIC. RESULTS: B2A-CIC values in APS-patients were 19.27 +/-
      2.6 AU vs 6.1 +/- 0.4 AU in blood donors (p < 0.001). There were 36.4% B2A-CIC
      positive patients (cutoff 21 AU) versus 5.5% in blood donors (p < 0.001).
      Dissociated IgA aB2GPI levels (total IgA aB2GPI) were 146.8 +/- 10.8 IU/mL in
      patients vs. 22.4 IU/mL in controls (p < 0.001). B2A-CIC was independent of B2GPI
      and autoantibodies IgA aB2GPI serum levels. CONCLUSION: B2A-CIC can be identified
      and quantified in an easy and reproducible manner using two complement
      independent methods. The use of these tests in prospective studies will allow
      better understanding of the prognosis and outcome of patients.

PMID- 25865264
TI  - Is the analysis of histamine and/or interleukin-4 release after isocyanate
      challenge useful in the identification of patients with IgE-mediated isocyanate
      asthma?
AB  - Isocyanates are a well-known and frequent cause of occupational asthma. The
      implementation of specific inhalation challenges (SICs) is the gold standard in
      asthma diagnosis supporting occupational case history, lung function testing,
      specific skin prick tests and the detection of specific IgE. However, the
      diagnosis is not always definitive. An interesting new approach, analyses of
      individual genetic susceptibilities, requires discrimination between a positive
      SIC reaction arising from IgE-mediated immune responses and one from other
      pathophysiological mechanisms. Hence, additional refinement tools would be
      helpful in defining sub-classes of occupational asthma and diagnosis. We used
      total IgE levels, specific IgE and SIC results for sub-classification of 27
      symptomatic isocyanate workers studied. Some mutations in glutathione S
      transferases (GSTs) are suspected either to enhance or to decrease the individual
      risk in the development of isocyanate asthma. Our patient groups were assessed
      for the point mutations GSTP1*I105V and GSTP1*A114V as well as deletions (null
      mutations) of GSTM1 and GSTT1. There seems to be a higher risk in developing IgE
      mediated reactions when GSTM1 is deleted, while GSTT1 deletions were found more
      frequently in the SIC positive group. Blood samples taken before SIC, 30-60 min
      and 24h after SIC, were analyzed for histamine and IL-4, classical markers for
      the IgE-mediated antigen-specific activation of basophils or mast cells. We
      suggest that the utility of histamine measurements might provide an additional
      useful marker reflecting isocyanate-induced cellular reactions (although the
      sampling times require optimization). The promising measurement of IL-4 is not
      feasible at present due to the lack of a reliable, validated assay.

PMID- 25865266
TI  - Identifying unstable taxa: Efficient implementation of triplet-based measures of
      stability, and comparison with Phyutility and RogueNaRok.
AB  - This paper describes an efficient implementation of triplet-based measures of
      stability, in the program TNT. The only available implementations of such
      measures are much slower than the present one, either because of an inefficient
      implementation (Phyutility, Thor) or because the stability is evaluated with
      quartets (RogueNaRok, requiring O(t(4)), instead of the O(t(3)) possible for
      triplets). The method to quickly calculate triplets is applied to solving IterPCR
      (Pol and Escapa, 2009). It is shown that, in some cases, IterPCR or other
      algorithms in the program TNT (e.g. commands prunnelsen, prunmajor, or chkmoves)
      produce more informative results than analysis with RogueNaRok. 

PMID- 25865265
TI  - Plant-based production of two chimeric monoclonal IgG antibodies directed against
      immunodominant epitopes of Vibrio cholerae lipopolysaccharide.
AB  - We have produced and characterized two chimeric human IgG1 monoclonal antibodies
      that bind different immunodominant epitopes on Vibrio cholerae lipopolysaccharide
      (LPS). MAb 2D6 IgG1 recognizes Ogawa O-polysaccharide antigen, while mAb ZAC-3
      IgG1 recognizes core/lipid A moiety of Ogawa and Inaba LPS. Both antibodies were
      expressed using a Nicotiana benthamiana-based rapid antibody-manufacturing
      platform (RAMP) and evaluated in vitro for activities associated with immunity to
      V. cholerae, including vibriocidal activity, bacterial agglutination and motility
      arrest. 

PMID- 25865267
TI  - Acquired Neonatal Chikungunya Encephalopathy.

PMID- 25865268
TI  - Improved revascularization of islet grafts using an angiogenic monocyte
      subpopulation derived from spheroid culture of bone marrow mononuclear cells.
AB  - The spheroid culture method is an effective strategy for ex vivo expansion of an
      autologous therapeutic cell population. We investigated if cotransplantation of
      bone marrow-derived spheroids (BM-spheroid) formed using 3D culture of BM-derived
      mononuclear cells (BM-MNCs) could improve the posttransplant outcome of islet
      grafts using a mouse syngeneic marginal mass renal subcapsular islet
      transplantation model. Using green fluorescent protein transgenic (GFP-Tg) mice,
      the role of the BM-spheroids and the contribution of vessels derived from donors
      and recipients in grafted areas were assessed by immunohistochemistry. Compared
      to fresh BM-MNCs and nonspheroid remnant cells (BM-nonspheroid), the BM
      spheroids, mainly composed of CXCR4(+) CD14(+) myeloid cells, showed higher
      angiogenic capacity, such as in vitro self-formed vessel structures; increased
      expression of angiogenic and chemoattractive factors; and incorporation into new
      vessel formation in basement membrane matrix plugs. BM-spheroid cotransplantation
      with islets improved the posttransplant outcomes in terms of glucose tolerance,
      serum insulin level, and diabetes reversal rate when compared with
      cotransplantation of BM-nonspheroids. Immunohistochemistry revealed that
      cotransplantation of the BM-spheroids increased vessel density, area of grafted
      endocrine and non-endocrine tissue, and beta cell proliferation. In conclusion,
      cotransplantation of islets and BM-spheroids improved islet function through
      facilitation of revascularization and an increase in cell proliferation and islet
      cell mass. 

PMID- 25865269
TI  - The importance of pollinators and autonomous self-fertilisation in the early
      stages of plant invasions: Banksia and Hakea (Proteaceae) as case studies.
AB  - Reproduction is a crucial stage in the naturalisation of introduced plant
      species. Here, using breeding system experiments and observations of floral
      visitors, we investigate whether a lack of pollinators or an inability to
      autonomously self-fertilise limits naturalisation in five Australian Banksia
      species and the co-familial Hakea salicifolia in South Africa. Banksia species
      were heavily utilised by native insects and nectar-feeding birds. Although
      Banksia produced fruit when pollinators were excluded, pollinators significantly
      increased seed set in four of the five species. H. salicifolia flowers were
      visited by 11 insect species; honeybees (Apis mellifera) were the main visitors.
      Flowers in naturalised H. salicifolia populations received almost four times the
      number of visits as flowers in non-naturalised populations; the latter showed
      both pollen limitation (PLI 0.40) and partial self-incompatibility. This should
      not prevent invasion, since H. salicifolia produces fruits via autonomous selfing
      in the absence of pollinators. The results suggest a limited role of breeding
      systems in mediating naturalisation of introduced Proteaceae species. Other
      factors, such as features of the recipient environments, appear to be more
      important. Spatial variation in rates of reproduction might, however, explain
      variation in the extent and rate of naturalisation of different populations. 

PMID- 25865271
TI  - Can Lipid Tissues Including Epicardial Adipose Tissue (EAT), Visceral Adipose
      Tissue (VAT) and Coronary Plaque Be Moving in the Same Direction?

PMID- 25865270
TI  - Contemporary evolution of resistance at the major insecticide target site gene
      Ace-1 by mutation and copy number variation in the malaria mosquito Anopheles
      gambiae.
AB  - Functionally constrained genes are ideal insecticide targets because disruption
      is often fatal, and resistance mutations are typically costly. Synaptic
      acetylcholinesterase (AChE) is an essential neurotransmission enzyme targeted by
      insecticides used increasingly in malaria control. In Anopheles and Culex
      mosquitoes, a glycine-serine substitution at codon 119 of the Ace-1 gene confers
      both resistance and fitness costs, especially for 119S/S homozygotes. G119S in
      Anopheles gambiae from Accra (Ghana) is strongly associated with resistance, and,
      despite expectations of cost, resistant 119S alleles are increasing significantly
      in frequency. Sequencing of Accra females detected only a single Ace-1 119S
      haplotype, whereas 119G diversity was high overall but very low at non-synonymous
      sites, evidence of strong purifying selection driven by functional constraint.
      Flanking microsatellites showed reduced diversity, elevated linkage
      disequilibrium and high differentiation of 119S, relative to 119G homozygotes
      across up to two megabases of the genome. Yet these signals of selection were
      inconsistent and sometimes weak tens of kilobases from Ace-1. This unexpected
      finding is attributable to apparently ubiquitous amplification of 119S alleles as
      part of a large copy number variant (CNV) far exceeding the size of the Ace-1
      gene, whereas 119G alleles were unduplicated. Ace-1 CNV was detectable in
      archived samples collected when the 119S allele was rare in Ghana. Multicopy
      amplification of resistant alleles has not been observed previously and is likely
      to underpin the recent increase in 119S frequency. The large CNV compromised
      localization of the strong selective sweep around Ace-1, emphasizing the need to
      integrate CNV analysis into genome scans for selection. 

PMID- 25865272
TI  - Advances in coronary physiology.
AB  - Pressure-wire technology, most typically fractional flow reserve (FFR), has
      provided interventional cardiologists with a means of determining the
      physiological importance of a stenosis during angiography. There has been renewed
      interest in coronary physiology in the light of guideline recognition, ongoing
      clinical research and new technologies changing the paradigm of how assessment is
      performed in the catheter laboratory. We reflect on FFR, with regards the
      potential effects of changing hemodynamics on FFR and the latest evidence with
      regards to outcomes. We also review the instantaneous wave-free ratio (iFR), a
      new pressure-only index, measured at rest, that is under active evaluation in
      several international randomized controlled trials. We review the accumulated
      evidence and discuss the important physiological concepts between pressure and
      flow that underlie the approach to using resting indices. Finally we investigate
      future developments, including physiological mapping with iFR-Pullback and the
      potential to predict the hemodynamic effect of stenting.

PMID- 25865273
TI  - Glycemic variability and cardiac remodeling in patients with acute myocardial
      infarction.

PMID- 25865274
TI  - Enveloped virus flocculation and removal in osmolyte solutions.
AB  - Our ability to reduce infectious disease burden throughout the world has been
      greatly improved by the creation of vaccines. However, worldwide immunization
      rates are low. The two most likely reasons are the lack of sufficient
      distribution in underdeveloped countries and the high cost of vaccine products.
      The high costs are due to the difficulties of manufacturing individual vaccine
      products with specialized purification trains. In this study, we propose to use
      virus flocculation in osmolytes, followed by microfiltration, as an alternative
      vaccine purification operation. In our previous work, we demonstrated that
      osmolytes preferentially flocculate a non-enveloped virus, porcine parvovirus
      (PPV). In this work we show that osmolytes flocculate the enveloped virus,
      Sindbis virus heat resistant strain (SVHR), and demonstrate a >80% removal with a
      0.2 MUm microfilter membrane while leaving proteins in solution. The best
      osmolytes were tested for their ability to flocculate SVHR at different
      concentrations, pH and ionic strengths. Our best removal was 98% of SVHR in 0.3M
      mannitol at a pH of 5. We propose that osmolytes are able to flocculate
      hydrophobic non-enveloped and enveloped virus particles by the reduction of the
      hydration layer around the particles, which stimulates virus aggregation. Now
      that we have demonstrated that protecting osmolytes flocculate viruses, this
      method has the potential to be a future platform purification process for
      vaccines.

PMID- 25865276
TI  - Draft genome of the xanthan producer Xanthomonas campestris NRRL B-1459 (ATCC
      13951).
AB  - Xanthomonas campestris NRRL B-1459 was used in pioneering studies related to the
      biotechnological production of xanthan, the commercially most important
      polysaccharide of bacterial origin. The analysis of its genome revealed a 5.1Mb
      chromosome plus the first complete plasmid of an X. campestris strain applied in
      biotechnology. 

PMID- 25865275
TI  - Enhanced extraction of bovine serum albumin with aqueous biphasic systems of
      phosphonium- and ammonium-based ionic liquids.
AB  - Novel aqueous biphasic systems (ABS) composed of phosphonium- or ammonium-based
      ionic liquids (ILs), combined with a buffered aqueous solution of potassium
      citrate/citric acid (pH=7.0), were investigated for the extraction of proteins.
      For that purpose, the phase diagrams, tie-lines and tie-line lengths were
      determined at 25  degrees C, and the performance of these ABS for the extraction
      of bovine serum albumin (BSA) was then evaluated. The obtained results reveal
      that, with the exception of the more hydrophobic ILs, most of the systems
      investigated allow the complete extraction of BSA for the IL-rich phase in a
      single-step. These remarkable extraction efficiencies are far superior to those
      afforded by more conventional extraction systems previously reported. The
      composition of the biphasic systems, i.e., the amount of phase-forming
      components, was also investigated aiming at reducing the overall costs of the
      process without losing efficiency on the protein extraction. It is shown that the
      extraction efficiencies of BSA are maintained at 100% up to high protein
      concentrations (at least up to 10 g L(-1)). The recovery of the BSA from the IL
      rich phase by dialysis is also shown in addition to the demonstration of the IL
      recyclability and reusability, at least for 3 times. In the sequential three-step
      extractions (BSA recovery/IL reusability), the extraction efficiencies of BSA for
      the IL-rich phase were maintained at 100%. For the improved ABS, the preservation
      of the protein native conformation was confirmed by Size Exclusion High
      Performance Liquid Chromatography (used also as the quantification method) and by
      Fourier Transform Infra-Red spectroscopy. According to the results herein
      reported, ABS composed of phosphonium- or ammonium-based ILs and a biodegradable
      organic salt represent an alternative and remarkable platform for the extraction
      of BSA and may be extended to other proteins of interest.

PMID- 25865277
TI  - Construction of CoA-dependent 1-butanol synthetic pathway functions under aerobic
      conditions in Escherichia coli.
AB  - 1-Butanol is an important industrial platform chemical and an advanced biofuel.
      While various groups have attempted to construct synthetic pathways for 1-butanol
      production, efforts to construct a pathway that functions under aerobic
      conditions have met with limited success. Here, we constructed a CoA-dependent 1
      butanol synthetic pathway that functions under aerobic conditions in Escherichia
      coli, by expanding the previously reported (R)-1,3-butanediol synthetic pathway.
      The pathway consists of phaA (acetyltransferase) and phaB (NADPH-dependent
      acetoacetyl-CoA reductase) from Ralstonia eutropha, phaJ ((R)-specific enoyl-CoA
      hydratase) from Aeromonas caviae, ter (trans-enoyl-CoA reductase) from Treponema
      denticola, bld (butylraldehyde dehydrogenase) from Clostridium
      saccharoperbutylacetonicum, and inherent alcohol dehydrogenase(s) from E. coli.
      To evaluate the potential of this pathway for 1-butanol production, culture
      conditions, including volumetric oxygen transfer coefficient (kLa) and pH were
      optimized in a mini-jar fermenter. Under optimal conditions, 1-butanol was
      produced at a concentration of up to 8.60gL(-1) after 46h of fed-batch
      cultivation. 

PMID- 25865278
TI  - Chloroplast degradation: one organelle, multiple degradation pathways.
AB  - Degradation of chloroplasts is a hallmark of both natural and stress-induced
      plant senescence. Autophagy and senescence-associated vacuoles are two
      established cellular pathways for chloroplast degradation. Recently, a third
      independent pathway for chloroplast degradation was reported. Here we will
      discuss this new discovery in relation to the other known pathways. 

PMID- 25865279
TI  - Interview with Marcel Dicke: the Droste effect in science.

PMID- 25865280
TI  - Circulating proplatelets in a patient with acute blood loss following liver
      transplantation.

PMID- 25865281
TI  - The mean lung dose (MLD) : predictive criterion for lung damage?
AB  - AIM: The purpose of this work was to prove the validity of the mean lung dose
      (MLD), widely used in clinical practice to estimate the lung toxicity of a
      treatment plan, by reevaluating experimental data from mini pigs. MATERIALS AND
      METHODS: A total of 43 mini pigs were irradiated in one of four dose groups (25,
      29, 33, and 37 Gy). Two regimens were applied: homogeneous irradiation of the
      right lung or partial irradiation of both lungs-including parts with lower dose
      but with similar mean lung doses. The animals were treated with five fractions
      with a linear accelerator applying a CT-based treatment plan. The clinical lung
      reaction (breathing frequency) and morphological changes in CT scans were
      examined frequently during the 48 weeks after irradiation. RESULTS: A clear dose
      effect relationship was found for both regimens of the trial. However, a
      straightforward relationship between the MLD and the relative number of
      responders with respect to different grades of increased breathing frequency for
      both regimens was not found. A morphologically based parameter NTCPlung was found
      to be more suitable for this purpose. The dependence of this parameter on the MLD
      is markedly different for the two regimens. CONCLUSION: In clinical practice, the
      MLD can be used to predict lung toxicity of a treatment plan, except for dose
      values that could lead to severe side effects. In the latter mentioned case,
      limitations to the predictive value of the MLD are possible. Such severe
      developments of a radiation-induced pneumopathy are better predicted by the
      NTCPlung formalism. The predictive advantage of this parameter compared to the
      MLD seems to remain in the evaluation and comparison of widely differing dose
      distributions, like in the investigated trial.

PMID- 25865282
TI  - Dynamic imaging of the growth plate cartilage reveals multiple contributors to
      skeletal morphogenesis.
AB  - The diverse morphology of vertebrate skeletal system is genetically controlled,
      yet the means by which cells shape the skeleton remains to be fully illuminated.
      Here we perform quantitative analyses of cell behaviours in the growth plate
      cartilage, the template for long bone formation, to gain insights into this
      process. Using a robust avian embryonic organ culture, we employ time-lapse two
      photon laser scanning microscopy to observe proliferative cells' behaviours
      during cartilage growth, resulting in cellular trajectories with a spreading
      displacement mainly along the tissue elongation axis. We build a novel software
      toolkit of quantitative methods to segregate the contributions of various
      cellular processes to the cellular trajectories. We find that convergent
      extension, mitotic cell division, and daughter cell rearrangement do not
      contribute significantly to the observed growth process; instead, extracellular
      matrix deposition and cell volume enlargement are the key contributors to
      embryonic cartilage elongation. 

PMID- 25865283
TI  - Predictors of type 2 diabetes among Taiwanese women with prior gestational
      diabetes mellitus.
AB  - AIM: The aims of this study were to determine the blood glucose screening rate of
      Taiwanese post-partum women with gestational diabetes (GDM) and to identify the
      predictors of type 2 diabetes among Taiwanese women with GDM. METHODS: The
      medical records of 130 women with GDM, who were delivered at a hospital in
      southern Taiwan between 1997 and 2010, were retrospectively reviewed. The GDM
      diagnosis was performed according to the National Diabetes Data Group and Expert
      Committee Criteria. The 2010 American Diabetes Association diabetes diagnosis
      criteria were used to determine whether post-partum women subsequently developed
      type 2 diabetes. RESULTS: In total, 71 records (54.6%) included blood glucose
      testing after childbirth between the first month and the ninth year, and 29
      records (22.3%) documented subsequent type 2 diabetes. In a multiple logistic
      regression analysis, the patients' pre-pregnancy body mass indices and insulin
      use during pregnancy were independently associated with subsequent type 2
      diabetes. CONCLUSION: In this study, documentation during pregnancy, which could
      have provided beneficial insights, was limited. Healthcare professionals should
      develop a program to improve the post-partum follow-up of women diagnosed with
      GDM.

PMID- 25865284
TI  - Effect of Hydrophobic Side Chains in the Induction of Immune Responses by
      Nanoparticle Adjuvants Consisting of Amphiphilic Poly(gamma-glutamic acid).
AB  - The new generation vaccines are safe but poorly immunogenic, and thus they
      require the use of adjuvants. Adjuvants that can control the balance and
      induction level of cellular and humoral immunities are urgently required for the
      treatment of and/or protection from infectious diseases and cancers. However,
      there are no adjuvants which can achieve these requirements. In this study,
      amphiphilic poly(gamma-glutamic acid) (gamma-PGA) with various kinds of
      hydrophobic amino acid ethyl esters (AAE) was synthesized (gamma-PGA-AAE) and
      used to prepare antigen-encapsulated nanoparticles (NPs). gamma-PGA-graft-Leu
      (gamma-PGA-Leu, where Leu = leucine ethyl ester), gamma-PGA-graft-Phe (gamma-PGA
      Phe, where Phe = phenylalanine ethyl ester), and gamma-PGA-graft-Trp (gamma-PGA
      Trp, where Trp = tryptophan ethyl ester) formed monodispersed NPs that
      encapsulated ovalbumin (OVA). The type and the induction level of the antigen
      specific cellular and humoral immunities could be controlled by the kinds of
      hydrophobic segments and vaccine formulation (encapsulation or mixture) used.
      When OVA was encapsulated into NPs, the cellular immunity was dominantly induced,
      while humoral immunity was dominant when OVA was mixed with NPs. These results
      are a first report to demonstrate that the balance and induction level of
      cellular and humoral immunities could be controlled by modifying compositions of
      NPs and vaccine formulation. Our results suggest that gamma-PGA-AAE NPs can
      provide safe and efficient nanoparticle-based vaccine adjuvants, and the results
      also provide guidelines in the rational design of amphiphilic polymers as vaccine
      adjuvants which can control the balance of immune responses. 

PMID- 25865285
TI  - What lies beneath.

PMID- 25865286
TI  - An organic-ligand-free thermochromic luminescent cuprous iodide trinuclear
      cluster: evidence for cluster centered emission and configuration distortion with
      temperature.
AB  - An organic-ligand-free cuprous iodide trinuclear cluster with significant
      temperature-dependent structural distortion has been synthesized and
      characterized, which shows thermochromic luminescence originating from a single
      cluster-centered triplet due to the absence of an organic ligand. This compound
      also shows interesting reversible temperature dependent phase transition from
      chiral to centrosymmetric space groups. 

PMID- 25865287
TI  - Morphology successfully separates third instar larvae of Muscina.
AB  - Three representatives of the muscid genus Muscina Robineau-Desvoidy (Diptera:
      Musicidae), Muscina levida (Harris), Muscina prolapsa (Harris) and Muscina
      stabulans (Fallen), are well known for their medical, veterinary and forensic
      importance. However, data in the literature provide contradictory information for
      the identification of third instar larvae of these species. This hinders easy
      species differentiation because it requires the rearing of material to adult
      stages in order to facilitate reliable identification. Third instar larvae of
      these three Muscina species were studied in detail using light and scanning
      electron microscopy to provide thorough redescriptions of their morphology.
      Existing information concerning third instar morphology, with particular
      reference to its value for taxonomy and identification, is revised and discussed.
      Emden's spiracular distance factor (SDF) is considered here as inappropriate for
      identification purposes in third instar larvae of Muscina spp. because its values
      are not constant ratios but increase during larval maturation and overlap in the
      examined species. These species were, instead, discriminated here by differences
      in the spinulation patterns of their abdominal segments. 

PMID- 25865288
TI  - A novel mutation in the FERMT1 gene in Turkish siblings with Kindler syndrome.

PMID- 25865289
TI  - Disseminated Scedosporium apiospermum infection in a near-drowning patient.

PMID- 25865290
TI  - Bioinspired magnetite formation from a disordered ferrihydrite-derived precursor.
AB  - We show that by reacting ferrihydrite (FeH) with Fe((II)) ions and subsequently
      increasing the pH, magnetite is formed through a multi-step nucleation process
      mediated by monodisperse FeH-Fe((II)) primary particles. The interaction of these
      primary particles with a transient green rust phase leads to the formation of
      smaller secondary particles which form the feedstock for magnetite formation.
      Surprisingly, the presence of a polypeptide additive prevents the formation of
      green rust as an Fe((II))-rich intermediate phase, and leads to the formation of
      amorphous aggregates of FeH-Fe((II)) particles which subsequently transform into
      the final magnetite nanocrystals. The observation of multiple transitions and the
      involvement of disordered precursor phases in this bioinspired crystallization
      route is important for our understanding of the nucleation of magnetite in
      geological and biological environments, and may lead to new approaches in the
      sustainable synthesis of this technologically important mineral. 

PMID- 25865291
TI  - Salivary and serum insulin-like growth factor (IGF-1) assays in anorexic
      patients.
AB  - OBJECTIVES: The purpose of this study was to measure the salivary and serum free
      IGF-1 concentration of patients with anorexia nervosa (AN) in comparison to an
      average population. METHODS: A controlled clinical trial was designed for an age-
      and gender-matched group of 121 AN patients and 77 healthy individuals. A
      clinical examination was made and blood and salivary samples were taken during
      the acute stage of AN (BMI < 15 kg/m2) in the first week of hospitalization. An
      enzyme immunoassay (ELISA) suitable for measuring free IGF-1 was used. RESULTS:
      Anorexic patients had significant reductions in salivary unstimulated flow rate
      (UFR), pH and free IGF-1 levels in their saliva and serum. Significant
      correlations between serum IGF-1 and BMI; salivary IGF-1 and UFR and pH were
      detected. CONCLUSIONS: Salivary and serum IGF-1 analyses appear to be a reliable
      biochemical indicator of malnutrition in AN patients. Measurement of salivary IGF
      1 levels would allow new perspectives in monitoring AN in its early stages.

PMID- 25865293
TI  - Safe Removal of a Broken Abutment Screw with Customized Drill Guide and Rotary
      Instrument: A Clinical Report.
AB  - This clinical report introduces a method for safe retrieval of a broken implant
      abutment screw. A reverse-tapping rotary instrument has been introduced in the
      market and is widely used to retrieve broken screws; however, it is difficult to
      use the rotary instrument unless an access hole for engagement of the rotary
      instrument is positioned directly on the center of the top of the broken screw
      remnant. Poor visibility is another limitation to make an access hole. To keep
      the position of the rotary instrument at the center of the broken screw, a
      customized drill guide was fabricated, modifying an implant impression coping
      with self-cured acrylic resin, all easily found in daily practice. The broken
      screw was easily removed, not damaging the internal threads of the implant. This
      technique could be applied to most implant systems when a specific removal kit
      for each implant system is not prepared. 

PMID- 25865292
TI  - Continuous subcutaneous insulin infusion in diabetes: patient populations,
      safety, efficacy, and pharmacoeconomics.
AB  - The level of glycaemic control necessary to achieve optimal short-term and long
      term outcomes in subjects with type 1 diabetes mellitus (T1DM) typically requires
      intensified insulin therapy using multiple daily injections or continuous
      subcutaneous insulin infusion. For continuous subcutaneous insulin infusion, the
      insulins of choice are the rapid-acting insulin analogues, insulin aspart,
      insulin lispro and insulin glulisine. The advantages of continuous subcutaneous
      insulin infusion over multiple daily injections in adult and paediatric
      populations with T1DM include superior glycaemic control, lower insulin
      requirements and better health-related quality of life/patient satisfaction. An
      association between continuous subcutaneous insulin infusion and reduced
      hypoglycaemic risk is more consistent in children/adolescents than in adults. The
      use of continuous subcutaneous insulin infusion is widely recommended in both
      adult and paediatric T1DM populations but is limited in pregnant patients and
      those with type 2 diabetes mellitus. All available rapid-acting insulin analogues
      are approved for use in adult, paediatric and pregnant populations. However,
      minimum patient age varies (insulin lispro: no minimum; insulin aspart: >=2
      years; insulin glulisine: >=6 years) and experience in pregnancy ranges from
      extensive (insulin aspart, insulin lispro) to limited (insulin glulisine).
      Although more expensive than multiple daily injections, continuous subcutaneous
      insulin infusion is cost-effective in selected patient groups. This comprehensive
      review focuses on the European situation and summarises evidence for the efficacy
      and safety of continuous subcutaneous insulin infusion, particularly when used
      with rapid-acting insulin analogues, in adult, paediatric and pregnant
      populations. The review also discusses relevant European guidelines; reviews
      issues that surround use of this technology; summarises the effects of continuous
      subcutaneous insulin infusion on patients' health-related quality of life;
      reviews relevant pharmacoeconomic data; and discusses recent advances in pump
      technology, including the development of closed-loop 'artificial pancreas'
      systems. (c) 2015 The Authors. Diabetes/Metabolism Research and Reviews Published
      by John Wiley & Sons Ltd. 

PMID- 25865294
TI  - Oxytocin reduces caloric intake in men.
AB  - OBJECTIVE: Preclinical studies indicate that oxytocin is anorexigenic and has
      beneficial metabolic effects. Oxytocin effects on nutrition and metabolism in
      humans are not well defined. It was hypothesized that oxytocin would reduce
      caloric intake and appetite and alter levels of appetite-regulating hormones.
      Metabolic effects of oxytocin were also explored. METHODS: A randomized, placebo
      controlled crossover study of single-dose intranasal oxytocin (24 IU) in 25
      fasting healthy men was performed. After oxytocin/placebo, subjects selected
      breakfast from a menu and were given double portions. Caloric content of food
      consumed was measured. Visual analog scales were used to assess appetite, and
      blood was drawn for appetite-regulating hormones, insulin, and glucose before and
      after oxytocin/placebo. Indirect calorimetry assessed resting energy expenditure
      (REE) and substrate utilization. RESULTS: Oxytocin reduced caloric intake with a
      preferential effect on fat intake and increased levels of the anorexigenic
      hormone cholecystokinin without affecting appetite or other appetite-regulating
      hormones. There was no effect of oxytocin on REE. Oxytocin resulted in a shift
      from carbohydrate to fat utilization and improved insulin sensitivity.
      CONCLUSIONS: Intranasal oxytocin reduces caloric intake and has beneficial
      metabolic effects in men without concerning side effects. The efficacy and safety
      of sustained oxytocin administration in the treatment of obesity warrants
      investigation.

PMID- 25865295
TI  - RNA-Seq-based transcriptome analysis of stem development and dwarfing regulation
      in Agapanthus praecox ssp. orientalis (Leighton) Leighton.
AB  - Agapanthus praecox is a monocotyledonous ornamental bulb plant. Generally, the
      scape (inflorescence stem) length can develop more than 1m, however application
      400 mg.L(-1) paclobutrazol can shorten the length beyond 70%. To get a deeper
      insight into its dwarfism mechanism, de novo RNA-Seq technology has been
      employed, for the first time, to describe the scape transcriptome of A. praecox.
      We got 71,258 assembled unigenes, and 45,597 unigenes obtained protein functional
      annotation. Take the above sequencing results as a reference gene set, using RNA
      seq (quantification) technology analyzed gene expression profiles between the
      control and paclobutrazol-treated samples, and screened 2838 differentially
      expressed genes. GO, KEGG and MapMan pathway analyses indicated that these
      differentially expressed genes were significantly enriched in response to
      stimulus, hormonal signaling, carbohydrate metabolism, cell wall, cell size, and
      cell cycle related biological process. To validate the expression profiles
      obtained by RNA-Seq, real-time qPCR was performed on 24 genes selected from key
      significantly enriched pathways. Comprehensive analysis suggested that
      paclobutrazol blocks GA signal that can effectively inhibit scape elongation; the
      GA signal interact with other hormonal signals including auxin, ethylene,
      brassinosteroid and cytokinins, and trigger downstream signaling cascades leading
      to metabolism, cell wall biosynthesis, cell division and the cycle decreased
      obviously, and finally induced dwarfism trait. Furthermore, AP2/EREBP, bHLH,
      C2H2, ARR, WRKY and ARF family's transcription factors were involved in the
      regulation of scape development in A. praecox. This transcriptome dataset will
      serve as an important public information platform to accelerate research on the
      gene expression and functional genomics of Agapanthus.

PMID- 25865296
TI  - Transcriptome analysis of the mammary gland from GH transgenic goats during
      involution.
AB  - Mammary glands are organs for milk production in female mammals. Growth hormone
      (GH) is known to affect the growth and development of the mammary gland, as well
      as to increase milk production in dairy goats. This study performed a
      comprehensive expression profiling of genes expressed in the mammary gland of
      early involution GH transgenic (n=4) and non-transgenic goats (n=4) by RNA
      sequencing. RNA was extracted from mammary gland tissues collected at day 3 of
      involution. Gene expression analysis was conducted by Illumina RNA sequencing and
      sequence reads were assembled and analyzed using TopHat. FPKM (fragments per
      kilobase of exon per million) values were analyzed for differentially expressed
      genes using the Cufflinks package. Gene ontology analysis of differentially
      expressed genes was categorized using agriGO, while KEGG pathway analysis was
      performed with the online KEGG automatic annotation server. Our results revealed
      that 75% of NCBI goat annotated genes were expressed during early involution. A
      total of 18,323 genes were expressed during early involution in GH transgenic
      goats, compared with 18,196 expressed genes during early involution of non
      transgenic goats. In these expressed genes, the majority (17,589) were
      ubiquitously expressed in GH transgenic and non-transgenic goats. However, there
      were 745 differentially expressed genes, 421 of which were upregulated and 324
      were downregulated in GH transgenic goats. GO and KEGG pathway analysis showed
      that these genes were involved in mammary gland physiology, including cell
      adhesion molecules, ECM-receptor interaction, Jak-STAT signaling pathway, and fat
      metabolism. Our results demonstrated that the GH receptor was strongly affected
      in GH transgenic goats, which may activate the IGF-1/Stat3 signaling pathway.
      Overall, our study provided a global view of the transcriptome during involution
      of GH transgenic and non-transgenic goats, which increases our understanding of
      the biology of involution in the goat.

PMID- 25865297
TI  - Screening, cloning and expression analysis of a cellulase derived from the
      causative agent of hypertrophy sorosis scleroteniosis, Ciboria shiraiana.
AB  - A cellulase gene (KJ700939, CsCelA) from Ciboria shiraiana that is highly
      expressed during the infection of mulberry fruit was screened by quantitative
      real-time PCR (qRT-PCR). Using cDNA isolated from infected mulberry fruits as
      template, the full-length 1170-bp sequence of CsCelA was obtained, which encodes
      a 390-amino acid protein with a putative signal peptide of 24 amino acids. The
      998-bp fragment encoding the mature peptide of CsCelA was cloned into the
      multiple cloning site of the pPIC9K vector and overexpressed as an active protein
      of 55.3kDa in the methylotrophic yeast Pichia pastoris. The specific activity of
      induced supernatants of the recombinant cellulase (CsCelA) was 17.44U/ml and
      135U/g for freeze-dried powder. The Kmax and Vmax of CsCelA for sodium
      carboxymethylcellulose (CMC) were 4.6mg/ml and 107.2U/mg, respectively. The
      supernatant and freeze-dried powder of the recombinant cellulase exhibited stable
      activity from pH4.0 to 9.0, and at temperatures ranging from 30 degrees C to 55
      degrees C. Finally, the activity of the recombinant cellulase was assessed by
      enzymatic hydrolysis of the cell walls of mulberry leaves. CsCelA showed an endo
      cellulase mode of cleavage, as assessed by thin layer chromatography (TLC).

PMID- 25865298
TI  - Evaluation of housekeeping genes for normalizing real-time quantitative PCR
      assays in pig skeletal muscle at multiple developmental stages.
AB  - Quantitative PCR (qPCR) requires a constantly expressed housekeeping gene as an
      internal control, the expression of which is similar in different biological
      samples. In the present study, we evaluated the applicability and compared the
      consistency of the gene expression of 16 reference genes, i.e., 10 common and 6
      candidate genes, through qPCR assays in pig skeletal muscles at multiple
      developmental stages. The stability of these 16 potential reference genes was
      investigated using the geNorm and NormFinder methods. Our results indicated that
      DRAP1 and RNF7 were the most appropriate combination to normalize gene expression
      in the Yorkshire samples, the combination of DRAP1 and WSB2 were appropriate in
      the Tongcheng samples, H3F3A and DRAP1 in prenatal periods, DRAP1 and RNF7 in
      postnatal periods, and the combination of DRAP1 and WSB2 was most suitable for
      accurate normalization in whole samples. This result provides a strong basis for
      similar studies in pigs that explore the molecular mechanisms underlying skeletal
      muscle development.

PMID- 25865299
TI  - Association of miR-146a rs2910164 polymorphism with cardio-cerebrovascular
      diseases: A systematic review and meta-analysis.
AB  - The microRNA146a rs2910164 polymorphism has been associated with the development
      of cardio-cerebrovascular diseases (CCDs); however, the results were inconsistent
      among different studies. The present report was aimed to investigate the
      association between rs2910164 G/C polymorphism and the risk of CCDs. Based on the
      data extracted from 12 eligible studies with a total of 5433 CCD cases and 6278
      controls, we performed a meta-analysis to assess the diseases risk of rs2910164
      G/C polymorphism under allelic contrast (C vs. G), homozygote comparisons (CC vs.
      GG), heterozygote comparisons (GC vs. GG), dominant model (CC+GC vs. GG) and
      recessive models (CC vs. GC+GG) in fixed or random effects models. We also
      conducted pathway enrichment analyses using the putative and validated miR-146a
      interacting targets to explore the functional impacts of rs2910164. The current
      meta-analysis results showed that rs2910164 CC genotype has a decreased risk with
      overall cardiovascular diseases and the specific coronary artery disease.
      Stratified analysis based on ethnicity showed that the CC genotype has a
      decreased risk with CCDs in Chinese population, but has an increased risk with
      CCDs in Korean and Indian populations. The results from pathway enrichment
      analysis also revealed the association of rs2910164 G allele with heart function
      and disease related pathways. Our findings suggested that miR-146a CC genotype
      might be a protective factor for cardiovascular diseases in Chinese population,
      but a risk factor in Korean and Indian populations.

PMID- 25865300
TI  - Comparative analysis of the hepatopancreas transcriptome of grass carp
      (Ctenopharyngodon idellus) fed with lard oil and fish oil diets.
AB  - n-3 highly unsaturated fatty acids (n-3 HUFAs) have been shown to suppress lipid
      accumulation and improve protein utilization in grass carp; however, little is
      known about the underlying molecular mechanism. Hence, we analyzed the
      hepatopancreas transcriptome of grass carp (Ctenopharyngodon idellus) fed either
      lard oil (LO) or fish oil (FO) diets. RNA-seq data showed that 125 genes were
      significantly up-regulated and 107 were significantly down-regulated in the FO
      group. Among them, 17 lipid metabolism related genes, 12 carbohydrate metabolism
      related genes, and 34 protein metabolism related genes were selected. Lipid
      metabolism related genes, such as very long-chain acyl-CoA synthetase
      (ACSVL),carnitine O-palmitoyltransferase 1 (CPT1) and carnitine-acylcarnitine
      translocase (CACT), were up-regulated in the FO group. But the genes of
      diacylglycerol O-acyltransferase 2 (DGAT2) and stearoyl-CoA desaturase (SCD) were
      down-regulated. Down-regulation of glycolysis related genes, such as 6
      phosphofructokinase (PFK), phosphoglycerate kinase (PGK) and pyruvate
      dehydrogenase kinase (PDK), added with up-regulation of gluconeogenesis related
      genes, such as phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6
      phosphatase (G6Pase), suggests lower utilization of carbohydrate of the FO group.
      Besides, dietary FO also influenced the protein metabolism related genes, such as
      up-regulation of genes involved in digestion of dietary protein, mRNA
      transcription, protein translation and amino acid utilization, down-regulation of
      genes involved in mRNA degradation and ubiquitination of protein. Interestingly,
      the up-regulation of mitochondrial uncoupling protein 2 (UCP2) and down
      regulation of oxidative phosphorylation related genes (cytochrome c oxidase
      subunit 4 isoform 2 [COX4I2], HIG1 domain family member 1A [HIGD1A] and
      cytochrome-b5 reductase [CYB5R]) suggest that energy metabolism may be also
      influenced by dietary fatty acid composition. These findings presented here
      provide a comprehensive understanding of the molecular mechanisms governing the
      effects of fish oil in grass carp.

PMID- 25865301
TI  - Propionic acidemia in the Arab World.
AB  - The autosomal recessive disease propionic acidemia (PA) is an inborn error of
      metabolism with highly variable clinical manifestations, caused by a deficiency
      of propionyl-CoA carboxylase (PCC) enzyme, due to mutations in either PCCA or
      PCCB genes, which encode the alpha and beta subunits of the PCC enzyme,
      respectively. The classical clinical presentation consists of poor feeding,
      vomiting, metabolic acidosis, hyperammonemia, lethargy, neurological problems,
      and developmental delay. PA seems to be a prevalent disease in the Arab World.
      Arab patients with PA seem to have the same classical clinical picture for PA
      with distinctive associated complications and other diseases. Most of the
      mutations found in Arab patients seem to be specific to the Arab population, and
      not observed in other ethnic groups. In this review, I will discuss in details
      the clinical and molecular profile of Arab patients with PA. 

PMID- 25865302
TI  - MicroRNA-221 regulates endothelial nitric oxide production and inflammatory
      response by targeting adiponectin receptor 1.
AB  - Adiponectin exerts anti-atherosclerosis property through its 2 receptors (AdipoR1
      and AdipoR2). The mechanism regulating the expression of adiponectin receptors is
      unclear. Bioinformatics analysis showed that miR-221 targeted the 3'-untranslated
      region (3'UTR) of the AdipoR1 mRNA. The protein level and the mRNA level of
      AdipoR1 were reduced when miR-221 was expressed in human umbilical vein
      endothelial cells (HUVECs). Meanwhile, miR-221 repressed the activity of
      luciferase reporter containing the 3'UTR of AdipoR1. The inhibitory effect of miR
      221 was abolished when the miR-221 binding site within the AdipoR1 3'UTR was
      deleted. Overexpression of miR-221 inhibited adiponectin-stimulated nitric oxide
      (NO) production in HUVECs. Furthermore, miR-221 abolished the inhibitory effect
      of adiponectin on NF-kB activation and the expression of adhesion molecules.
      Altogether, these results indicated that miR-221 targets AdipoR1 to regulate
      endothelial inflammatory response.

PMID- 25865303
TI  - Y chromosomal haplotype characteristics of domestic sheep (Ovis aries) in China.
AB  - Investigations on the variation present at the male-specific Y chromosome region
      provide strong information to understand the origin and evolution of domestic
      sheep. One SNP OY1 (g.88A>G) in the upstream region of SRY gene, and the
      microsatellite SRYM18 locus within ovine Y chromosome were analyzed in one
      hundred and forty five samples collected from eleven breeds in China. SNP OY1 was
      analyzed using PCR-SSCP method and sequencing. Two different PCR-SSCP patterns
      represented two specific sequences with sequence analysis revealing SNP-OY1
      (g.88A>G) were observed, while SNP A-OY1 showed the most common frequency
      (82.8%). Sequencing of the SRYM18 region revealed one novel size fragment (A2)
      with different repetitive units. Seven haplotypes (H4, H5, H6, H7, H8, H9 and
      H12) and two novel haplotypes (Ha and Hb) were established using combined
      genotype analysis. H6 showed the highest frequency (43.4%) across all breeds, and
      H8 showed the second frequency (24.1%). Ha was only found in one breed (Tan),
      while Hb was present in three breeds (Gansu alpine, White Suffolk and Duolang).
      Our findings reveal one novel allele in SRYM18 region and two novel male
      haplotypes of domestic sheep in China. 

PMID- 25865304
TI  - Screening and identification of a DNA aptamer to concanavalin A and its
      application in food analysis.
AB  - Herein, a novel aptamer that targets concanavalin A (Con A), a plant lectin, is
      isolated using systematic evolution of ligands by an exponential enrichment
      (SELEX) technique. Nine rounds of SELEX screening over an agarose spin column
      have resulted in enrichment of eight sequences having high affinity to Con A. The
      highest affinity sequence was selected as a potent aptamer and characterized it
      in detail. The evolved Con A aptamer (Con A-aptabody) is a 41 nt ssDNA that binds
      the Con A specifically with a dissociation constant of 172.7 +/- 29.7 nM. In
      silico analyses predict the Con A-aptabody to form G-quadruplex due to its G-rich
      sequence (GGAAGGCGGAGGG). A detection method developed using Con A-aptabody is
      found to have a detection range of 10-750 ng/mL with limits of detection and
      quantification being 13.22 and 44.09 ng/mL, respectively. The utility of the
      method is demonstrated by analyzing jack bean (Canavalia ensiformis), kidney bean
      (Phaseolus vulgaris), wheat (Triticum spp.), mung bean (Vigna radiata), and
      lentil (Lens culinaris) for their Con A contents. Hence, the developed Con A
      aptabody provides a useful substitute to Con A-antibody for food analysis and
      related applications. 

PMID- 25865305
TI  - Liver transplantation in patients with end-stage liver disease requiring
      intensive care unit admission and intubation.
AB  - Data regarding transplantation outcomes in ventilated intensive care unit (ICU)
      dependent patients with end-stage liver disease (ESLD) are conflicting. This
      single-center cohort study investigated the outcomes of patients with ESLD who
      were intubated with mechanical support before liver transplantation (LT). The ICU
      plus intubation group consisted of 42 patients with decompensated cirrhosis and
      mechanical ventilation before transplantation. LT was considered for intubated
      ICU patients if the fraction of inspired oxygen was <=40% with a positive end
      expiratory pressure <= 10, low pressor requirements, and the absence of an active
      infection. Intubated ICU patients were compared to 80 patients requiring ICU
      admission before transplantation without intubation and to 126 matched non-ICU
      bound patients. Patients requiring ICU care with intubation and ICU care alone
      had more severe postoperative complications than non-ICU-bound patients.
      Intubation before transplantation was associated with more postoperative
      pneumonias (15% in intubated ICU transplant candidates, 5% in ICU-bound but not
      intubated patients, and 3% in control group patients; P = 0.02). Parameters of
      reperfusion injury and renal function on postoperative day (POD) 2 and POD 7 were
      similar in all groups. Bilirubin levels were higher in the ICU plus intubation
      group at POD 2 and POD 7 after transplantation but were normalized in all groups
      within 3 months. The ICU plus intubation group versus the ICU-only group and the
      non-ICU group had decreased 1-, 3-, and 5-year graft survival (81% versus 84%
      versus 92%, 76% versus 78% versus 87%, and 71% versus 77% versus 84%,
      respectively; P = 0.19), but statistical significance was not reached. A Glasgow
      coma scale score of <7 versus >7 before transplantation was associated with high
      postoperative mortality in ICU-bound patients requiring intubation (38% versus
      23%; P = 0.01). In conclusion, ICU admission and mechanical ventilation should
      not be considered contraindications for LT. With careful patient selection,
      acceptable long-term outcomes can be achieved despite increased postoperative
      complications.

PMID- 25865306
TI  - Important mitochondrial proteins in human omental adipose tissue show reduced
      expression in obesity.
AB  - Impaired mitochondrial function is important in obesity and the development of
      insulin resistance and diabetes. The aim of this study was to identify human
      adipocyte-derived mitochondrial proteins associated with obesity. Mitochondrial
      proteins from 20 abdominal omental adipose tissue biopsies (13 obese and 7
      control subjects) were separated by anion-exchange chromatography coupled to SDS
      PAGE. Protein contents were compared and identified by MALDI-TOF-TOF mass
      spectrometry. Proteins of interest were validated, verified and quantified using
      immuno dot blot assays in a total of 76 mitochondrial preparations from both
      obese and non-obese patients. Mass spectrometric comparison of 20 mitochondrial
      proteomes yielded 62 proteins that were differentially expressed in adipose
      tissue of obese subjects. The immunological quantification of 12 mitochondrial
      proteins from 76 omental adipose tissue biopsies revealed four proteins, citrate
      synthase, HADHA, LETM1 and mitofilin inversely being associated with BMI, and
      mitofilin being inversely correlated with gender. BIOLOGICAL SIGNIFICANCE: The
      finding that obese human subjects have reduced levels of important mitochondrial
      proteins in adipocytes of omental adipose tissue as compared to non-obese
      controls gives new insights in the impairment of mitochondrial function in this
      specialized compartment of human adipose tissue in obesity and may eventually
      lead to the definition of valuable obesity markers.

PMID- 25865307
TI  - Proteomic analysis of the palmitoyl protein thioesterase 1 interactome in SH-SY5Y
      human neuroblastoma cells.
AB  - Neuronal ceroid lipofuscinoses (NCL) are a group of inherited progressive
      childhood disorders, characterized by early accumulation of autofluorescent
      storage material in lysosomes of neurons or other cells. Clinical symptoms of NCL
      include: progressive loss of vision, mental and motor deterioration, epileptic
      seizures and premature death. CLN1 disease (MIM#256730) is caused by mutations in
      the CLN1 gene, which encodes palmitoyl protein thioesterase 1 (PPT1). In this
      study, we utilised single step affinity purification coupled to mass spectrometry
      (AP-MS) to unravel the in vivo substrates of human PPT1 in the brain neuronal
      cells. Protein complexes were isolated from human PPT1 expressing SH-SY5Y stable
      cells, subjected to filter-aided sample preparation (FASP) and analysed on a Q
      Exactive Hybrid Quadrupole-Orbitrap mass spectrometer. A total of 23 PPT1
      interacting partners (IP) were identified from label free quantitation of the MS
      data by SAINT platform. Three of the identified PPT1 IP, namely CRMP1, DBH, and
      MAP1B are predicted to be palmitoylated. Our proteomic analysis confirmed
      previously suggested roles of PPT1 in axon guidance and lipid metabolism, yet
      implicates the enzyme in novel roles including: involvement in neuronal migration
      and dopamine receptor mediated signalling pathway. BIOLOGICAL SIGNIFICANCE: The
      significance of this work lies in the unravelling of putative in vivo substrates
      of human CLN1 or PPT1 in brain neuronal cells. Moreover, the PPT1 IP implicate
      the enzyme in novel roles including: involvement in neuronal migration and
      dopamine receptor mediated signalling pathway.

PMID- 25865308
TI  - Molecular networking and pattern-based genome mining improves discovery of
      biosynthetic gene clusters and their products from Salinispora species.
AB  - Genome sequencing has revealed that bacteria contain many more biosynthetic gene
      clusters than predicted based on the number of secondary metabolites discovered
      to date. While this biosynthetic reservoir has fostered interest in new tools for
      natural product discovery, there remains a gap between gene cluster detection and
      compound discovery. Here we apply molecular networking and the new concept of
      pattern-based genome mining to 35 Salinispora strains, including 30 for which
      draft genome sequences were either available or obtained for this study. The
      results provide a method to simultaneously compare large numbers of complex
      microbial extracts, which facilitated the identification of media components,
      known compounds and their derivatives, and new compounds that could be
      prioritized for structure elucidation. These efforts revealed considerable
      metabolite diversity and led to several molecular family-gene cluster pairings,
      of which the quinomycin-type depsipeptide retimycin A was characterized and
      linked to gene cluster NRPS40 using pattern-based bioinformatic approaches. 

PMID- 25865309
TI  - Extracellular poly(ADP-ribose) is a pro-inflammatory signal for macrophages.
AB  - Poly(ADP-ribose) polymerase 1 (PARP1) synthesizes poly(ADP-ribose) (PAR), an
      essential post-translational modification whose function is important in many
      cellular processes including DNA damage signaling, cell death, and inflammation.
      All known PAR biology is intracellular, but we suspected it might also play a
      role in cell-to-cell communication during inflammation. We found that PAR
      activated cytokine release in human and mouse macrophages, a hallmark of innate
      immune activation, and determined structure-activity relationships. PAR was
      rapidly internalized by murine macrophages, while the monomer, ADP-ribose, was
      not. Inhibitors of Toll-like receptor 2 (TLR2) and TLR4 signaling blocked
      macrophage responses to PAR, and PAR induced TLR2 and TLR4 signaling in reporter
      cell lines suggesting it was recognized by these TLRs, much like bacterial
      pathogens. We propose that PAR acts as an extracellular damage associated
      molecular pattern that drives inflammatory signaling. 

PMID- 25865310
TI  - Antitumor activity of phenanthroindolizidine alkaloids is associated with
      negative regulation of Met endosomal signaling in renal cancer cells.
AB  - Met is a receptor tyrosine kinase for hepatocyte growth factor. Met mutations
      have been considered as a major cause of primary resistance to Met tyrosine
      kinase inhibitors (TKIs). Mutated Met enhances its endosomal signaling, which
      includes internalization, signaling within endosomes, recycling to membrane, and
      sorting for degradation. These sequential events lead to a plausible mechanism
      for resistance. (-)-Antofine, a phenanthroindolizidine alkaloid, has exhibited
      potent antitumor activity but the precise underlying mechanism has been poorly
      understood. We found that (-)-antofine effectively inhibited the proliferation of
      Met-mutated Caki-1 cells, which were resistant to well-known Met TKIs. (-)
      Antofine negatively regulated Met endosomal signaling and consequently inhibited
      the nuclear translocation of STAT3 both in vitro and in vivo. These findings
      emphasize the potential of Met endosomal signaling as a novel target for Met TKI
      resistant cancers and (-)-antofine as a novel lead compound associated with the
      suppression of Met endosomal signaling. 

PMID- 25865311
TI  - Tamoxifen inhibits CDK5 kinase activity by interacting with p35/p25 and modulates
      the pattern of tau phosphorylation.
AB  - Cyclin-dependent kinase 5 (CDK5) is a multifunctional enzyme that plays numerous
      roles, notably in brain development. CDK5 is activated through its association
      with the activators, p35 and p39, rather than by cyclins. Proteolytic procession
      of the N-terminal part of its activators has been linked to Alzheimer's disease
      and various other neuropathies. The interaction with the proteolytic product p25
      prolongs CDK5 activation and modifies the substrate specificity. In order to
      discover small-molecule inhibitors of the interaction between CDK5 and p25, we
      have used a bioluminescence resonance energy transfer (BRET)-based screening
      assay. Among the 1,760 compounds screened, the generic drug tamoxifen has been
      identified. The inhibition of the CDK5 activity by tamoxifen was notably
      validated by monitoring the phosphorylation state of tau protein. The study of
      the molecular mechanism of inhibition indicates that tamoxifen interacts with p25
      to block the CDK5/p25 interaction and pave the way for new treatments of
      tauopathies. 

PMID- 25865312
TI  - Unbiased proteomic profiling strategy for discovery of bacterial effector
      proteins reveals that Salmonella protein PheA is a host cell cycle regulator.
AB  - Salmonella utilizes a type III secretion system to inject bacterial effector
      proteins into the host cell cytosol. Once in the cytosol, these effectors hijack
      various biochemical pathways to regulate virulence. Despite the importance of
      effector proteins, especially for understanding host-pathogen interactions, a
      potentially large number of effectors are yet to be identified. Here, we
      demonstrate that unbiased chemical proteomic profiling using off-the-shelf
      fluorescent probes leads to the discovery of a host cell cycle regulator encoded
      in the Salmonella genome. Our profiling combined with bioinformatic analysis
      implicates 29 Salmonella as potential effectors. We follow up on the top
      candidate, chorismate mutase-P/prehenate dehydratase, PheA, and present evidence
      that PheA is an effector that mimics E2F7 transcription factor of the host cell
      and promotes G1/S cell cycle arrest. This validates our strategy and opens
      opportunities for effector identification in the future. 

PMID- 25865313
TI  - Longitudinal relationship between diabetes-specific emotional distress and follow
      up HbA1c in adults with Type 1 diabetes mellitus.
AB  - AIM: To examine whether diabetes-specific emotional distress was related to
      follow-up glycaemic control in adults with Type 1 diabetes mellitus. METHODS:
      Adults with Type 1 diabetes mellitus completed the Diabetes Distress Scale and
      reported sociodemographic information when attending a clinical consultation at a
      university endocrinology unit. Blood samples to determine baseline HbA1c were
      taken during consultations. All respondents' HbA1c measurements registered from
      January 2009 to December 2011 were collected from medical records. The
      relationship between baseline diabetes-specific emotional distress and HbA1c was
      examined with linear mixed-effects models in 175 patients with complete data.
      RESULTS: After controlling for confounders, baseline diabetes-specific emotional
      distress and glycaemic control were significantly associated (fixed-effect
      coefficient 0.40, P < 0.001) and the regimen-related distress subscale had the
      strongest association with glycaemic control (fixed-effect coefficient 0.47, P <
      0.001). The two-item measure of diabetes-specific distress had a weaker but still
      significant association with glycaemic control (fixed-effect coefficient 0.31, P
      < 0.001). None of these relationships was significant after adjusting for the
      baseline HbA1c . CONCLUSIONS: People with elevated baseline diabetes-specific
      emotional distress are at risk of prolonged suboptimum glycaemic control;
      therefore, elevated diabetes-specific emotional distress, especially regimen
      related distress, might be an important marker for prolonged suboptimum glycaemic
      control, and might indicate a need for special attention regarding patient self
      management.

PMID- 25865317
TI  - Ammonia Activation by a Nickel NCN-Pincer Complex featuring a Non-Innocent N
      Heterocyclic Carbene: Ammine and Amido Complexes in Equilibrium.
AB  - A Ni(0)-NCN pincer complex featuring a six-membered N-heterocyclic carbene (NHC)
      central platform and amidine pendant arms was synthesized by deprotonation of its
      Ni(II) precursor. It retained chloride in the square-planar coordination sphere
      of nickel and was expected to be highly susceptible to oxidative addition
      reactions. The Ni(0) complex rapidly activated ammonia at room temperature, in a
      ligand-assisted process where the carbene carbon atom played the unprecedented
      role of proton acceptor. For the first time, the coordinated (ammine) and
      activated (amido) species were observed together in solution, in a solvent
      dependent equilibrium. A structural analysis of the Ni complexes provided insight
      into the highly unusual, non-innocent behavior of the NHC ligand.

PMID- 25865315
TI  - The impact of covariate measurement error on risk prediction.
AB  - In the development of risk prediction models, predictors are often measured with
      error. In this paper, we investigate the impact of covariate measurement error on
      risk prediction. We compare the prediction performance using a costly variable
      measured without error, along with error-free covariates, to that of a model
      based on an inexpensive surrogate along with the error-free covariates. We
      consider continuous error-prone covariates with homoscedastic and heteroscedastic
      errors, and also a discrete misclassified covariate. Prediction performance is
      evaluated by the area under the receiver operating characteristic curve (AUC),
      the Brier score (BS), and the ratio of the observed to the expected number of
      events (calibration). In an extensive numerical study, we show that (i) the
      prediction model with the error-prone covariate is very well calibrated, even
      when it is mis-specified; (ii) using the error-prone covariate instead of the
      true covariate can reduce the AUC and increase the BS dramatically; (iii) adding
      an auxiliary variable, which is correlated with the error-prone covariate but
      conditionally independent of the outcome given all covariates in the true model,
      can improve the AUC and BS substantially. We conclude that reducing measurement
      error in covariates will improve the ensuing risk prediction, unless the
      association between the error-free and error-prone covariates is very high.
      Finally, we demonstrate how a validation study can be used to assess the effect
      of mismeasured covariates on risk prediction. These concepts are illustrated in a
      breast cancer risk prediction model developed in the Nurses' Health Study.

PMID- 25865318
TI  - Continuous molecular adsorbent recirculating system treatment in 69 patients
      listed for liver transplantation.
AB  - OBJECTIVE: The molecular adsorbent recirculating system (MARS) is used to purify
      blood from albumin-bound toxins in patients with liver failure. However, the
      application of MARS has not demonstrated improved survival in randomized clinical
      trials and the clinical utility has not been finally established. In our
      department, the use of MARS is now restricted to the most critically ill patients
      with acute or acute on chronic liver failure. MATERIAL AND METHODS: Since 2005,
      we have treated 69 patients (30 males/39 females with median age of 49 years
      ranging from 1 months to 70 years) listed for liver transplantation (LT) with
      MARS. Median model of end-stage liver disease score in patients older than 12
      years of age (n = 56) was 33 (interquartile range 26-39). The flow rate was 35-40
      mL/kg/h and treatment kits were changed every 8-12 h. The patients were treated
      for a median of 27 h (range 1-144 h). RESULTS: Fifty-six patients (81%) were
      transplanted. Nine died before they could be transplanted, and four patients
      recovered without transplantation. Forty-six (82%) of the transplanted patients
      were alive 30 days after transplantation. Ammonium decreased modestly from a
      median of 148 to 124 uM (p = 0.03) during MARS treatment. We detected worsening
      of coagulopathy with significant decreases in platelet count and fibrinogen
      concentrations, and increase in International Normalized Ratio. Phosphate and
      magnesium decreased significantly during MARS treatment. CONCLUSION: Continuous
      MARS therapy may bridge liver failure patients to LT under close observation and
      treatment of coagulopathy and electrolyte disturbances.

PMID- 25865319
TI  - The mental health of children orphaned by AIDS: a review of international and
      southern African research.
AB  - This paper reviews research on the mental health and psychological outcomes of
      children who are orphaned by AIDS. Studies are limited, scattered and often
      unpublished. The review focuses on research which is quantitative and based on
      primary research with uninfected children who are parentally bereaved by AIDS.
      Due to the limited available quantitative research in this area, both controlled
      and uncontrolled studies are included. Selected qualitative and related
      literature is also reviewed, with a focus on work relevant to the southern
      African context. This paper builds upon and updates Wild's seminal review,
      published in this journal in 2001 (Wild 2001). We found 24 studies worldwide,
      with wide variations in sample characteristics, outcome measurements and control
      groups. Three of these studies are ongoing. Internalising problems in orphaned
      children were found in 16 studies (of the 19 studies which measured them) and
      externalising problems were found in five studies (of 10 which measured them).
      There is a clear need for further, and rigorous, research into mental health, and
      risk and protective factors for children orphaned by AIDS. Furthermore, it is
      critical that research adopts a more coordinated approach, which allows for
      meaningful comparisons of child outcomes in different areas. 

PMID- 25865320
TI  - Photo-voice as a tool for analysis and activism in response to HIV and AIDS
      stigmatisation in a rural KwaZulu-Natal school.
AB  - OBJECTIVE: This paper focuses on the use of participatory approaches to research
      and intervention and explores the uses of photo-voice as a methodology and a
      means of promoting childhood and youth activism in the context of HIV and AIDS.
      METHOD: Photo-voice, a visual participatory methodology, was used with 21 Grade 8
      and 9 learners in one of three schools participating in a larger project, to
      identify, understand and interpret incidents related to stigma and discrimination
      against people living with and affected by HIV and AIDS, as well as the
      strategies proposed by the learners to possibly reduce stigma. RESULTS: Three
      themes emerged: awareness of HIV and AIDS, awareness of HIV-related stigma and
      its impacts, and acceptance of personal agency and taking action. CONCLUSIONS:
      Understandings of and perceptions about HIV and AIDS are improving, yet
      significant pockets of ignorance about the dynamics of HIV infection still remain
      among the youth. Negative attitudes towards people infected with and affected by
      the virus remain, and stigmatisation continues. The use of photo-voice and other
      participatory methodologies offers alternative strategies for involving youth in
      their own knowledge production, as well as in the development of an individual
      sense of agency for taking action.

PMID- 25865321
TI  - Home-based care for parents with AIDS: impact on children's psychological
      functioning.
AB  - OBJECTIVE: This study explored the concept of home-based care for people living
      with full-blown AIDS and the impact of this on their children's psychological
      functioning. There were 30 children in the study whose parents had full-blown
      AIDS. The comparison group comprised 30 children. The parents of the children in
      the comparison group reported that they did not have full-blown AIDS and were not
      registered as AIDS patients with their community home-based care group. METHOD:
      The children's psychological functioning and performance on cognitive tasks were
      examined, using the Impact of Event Scale - Revised, the Secondary Traumatic
      Stress Scale (STSS), the Stress Symptoms Checklist, the Child Behaviour Checklist
      (CBCL), the British Ability Scales and Daniel and Diack's Graded Spelling Test.
      RESULT: The results of the study showed that children whose parents had full
      blown AIDS showed mental distress and low cognitive performance on numerical and
      spelling skills. CONCLUSION: The findings of the study seem to suggest that
      although the home-based care concept is a noble and global idea, it should be
      accompanied by psychological support mechanisms to mitigate the effects of
      traumatic stress that normally follow exposure to a traumatic event. Suggestions
      for further research on the topic are discussed.

PMID- 25865322
TI  - Bullying in public secondary schools in Nairobi, Kenya.
AB  - BACKGROUND: The prevalence and frequency of bullying in Nairobi public secondary
      schools in particular and in Kenyan schools in general is not known. Knowledge of
      the extent of the problem is essential in developing effective interventions.
      AIM: To study the prevalence and frequency of bullying in Nairobi public
      secondary schools, Kenya. METHODS: A self-report sociodemographic questionnaire
      and the Olweus Bullying Questionnaire of 1991 were administered to 1 012 students
      from a stratified sample of public secondary schools in Nairobi. RESULTS: Between
      63.2% (640) and 81.8% (828) of students reported various types of bullying, both
      direct and indirect, with significant variations found for sex, age, class and
      year of study, whether in day or boarding school, and the place where bullied.
      Being bullied was significantly associated with becoming a bully, in turn.
      DISCUSSION: Bullying is highly prevalent in Kenyan schools. Further studies are
      needed to characterise bullies and victims in terms of personality and
      environmental factors that may be associated with or conducive to bullying, as
      well as to determine the long-term prognosis for both bullies and victims.
      Further research is also required to determine the most appropriate intervention.

PMID- 25865323
TI  - Youth violence risk assessment: gaps in local knowledge and directions for future
      research.
AB  - There is a lack of research on violence risk assessment in South Africa,
      particularly on the assessment of risk for violence in children and adolescents.
      This is problematic, because of the strong association between conducting sound
      assessments and the appropriate referral of youths to intervention programmes.
      Considering the very high levels of violence in our country, the effective
      treatment of violent youths is imperative. International literature on violence
      risk assessment indicates that although a number of instruments designed to
      assess youth violence risk exist, many primarily focus on identifying
      psychopathic tendencies in young people, which has stimulated much debate amongst
      scholars. In addition to paying careful attention to the content of youth
      violence risk instruments, their administration should be monitored, to ensure
      that assessment practice is up to standard. Future research efforts in South
      Africa should be dedicated towards testing the applicability of instruments
      developed internationally in local settings, and towards the development and
      testing of local instruments. 

PMID- 25865324
TI  - Childhood cancer: a parent's perspective on social support, with a case
      illustration.
AB  - When a child is diagnosed with cancer, parents enter unfamiliar terrain, where
      their basic childrearing tasks are challenged. Life changes from diagnosis
      onwards, through adjustment and then life beyond the illness. Provision of
      psychological support for the whole family after primary diagnosis is widely
      considered essential. The objective of this study was to explore a husband and
      wife's journey of coming to terms with their child's cancer, and to describe
      resources they used to get through this ordeal. The method used in this study was
      a case study, using narrative analysis. The positive influence of a social
      support group is discussed as the main coping mechanism for this family on their
      path to recovery. 

PMID- 25865326
TI  - The Handbook of Infant Mental Health (Second Edition) by Charles H Zeanah, Jr
      (editor).

PMID- 25865325
TI  - Africa's orphan crisis - is it the teacher's concern?
AB  - The fact that almost 15% of children in 11 of the 43 countries in sub-Saharan
      Africa are orphans is daunting indeed. This reality of large numbers of orphans
      should be one of sub-Saharan Africa's greatest concerns. It is not only the
      emotional impact of the pandemic that is at stake, but also the social and
      economic fabric of entire societies. Up until now, very little attention has been
      given to the fact that these children must grow towards adulthood without the
      guidance of their parents. The focus of this study is therefore formulated in the
      following research question: what do orphans need to reach adulthood, and how can
      teachers support them in reaching responsible adulthood? In identifying what
      defines adulthood in a specific context, the researcher has a closer look at the
      role of cultural value systems. The assumption is made that culture is a broad
      abstraction that includes a society's forms of knowledge, belief systems,
      languages, religion and values; these become imperative in guiding children
      towards adulthood. Deriving from this assumption that culture and context play a
      vital role in people's understanding of the concept of adulthood, one can assume
      that this understanding will be different for each particular group. In the
      absence of parents, the school can be seen as the most important agent (loco
      parentis) in addressing the needs of vulnerable children. Planning a curriculum
      that addresses the needs of these vulnerable children will have to be
      reconsidered. The full impact of the diversity of learners and their communities
      will have to be accommodated in all planning. As the number of orphans in schools
      increases, and the role of teachers in guiding these young learners to adulthood
      becomes more prominent, it is recommended that a thorough investigation be
      conducted into the importance of individual and community interpretations of
      'proper adulthood' within individual communities. 

PMID- 25865327
TI  - Child and adolescent therapy: cognitive behavioral procedures (third edition):
      edited by philip C kendall.

PMID- 25865328
TI  - Adolescence: assessing and promoting resilience in vulnerable children 3 by
      brigid daniel and sally wassell.

PMID- 25865330
TI  - Journal abstracts from current research in the field of child and adolescent
      mental health.

PMID- 25865329
TI  - A Question of Technique: Independent Psychoanalytic Approaches with Children and
      Adolescents Monica by Lanyado and Ann Horn (editors).

PMID- 25865331
TI  - Advocating for better mental health service provision for our children and their
      families.

PMID- 25865332
TI  - Psychotherapy in distressed communities.

PMID- 25865333
TI  - First principles investigation of the activity of thin film Pt, Pd and Au surface
      alloys for oxygen reduction.
AB  - Further advances in fuel cell technologies are hampered by kinetic limitations
      associated with the sluggish cathodic oxygen reduction reaction. We have
      investigated a range of different formulations of binary and ternary Pt, Pd and
      Au thin films as electrocatalysts for oxygen reduction. The most active binary
      thin films are near-surface alloys of Pt with subsurface Pd and certain PdAu and
      PtAu thin films with surface and/or subsurface Au. The most active ternary thin
      films are with pure metal Pt or Pd skins with some degree of Au in the surface
      and/or subsurface layer and the near-surface alloys of Au with mixed Pt-Pd skins.
      The activity of the binary and ternary catalysts is explained through weakening
      of the OH binding energy caused by solute elements. However, given the low alloy
      formation energies it may be difficult to tune and retain the composition under
      operating conditions. This is particularly challenging for alloys containing Au
      due to a high propensity of Au to segregate to the surface. We also show that
      once Au is on the surface it will diffuse to defect sites, explaining why small
      amounts of Au retard dissolution of Pt nanoparticles. For the PtPd thin films
      there is no pronounced driving force for surface segregation, diffusion to
      defects or surface self-assembling. On the basis of stability and activity
      analysis we conclude that the near surface alloy of Pd in Pt and some PdAu binary
      and PtPdAu ternary thin films with a controlled amount of Au are the best
      catalysts for oxygen reduction. 

PMID- 25865334
TI  - The therapeutic application of CRISPR/Cas9 technologies for HIV.
AB  - INTRODUCTION: The use of antiretroviral therapy has led to a significant decrease
      in morbidity and mortality in HIV-infected individuals. Nevertheless, gene-based
      therapies represent a promising therapeutic paradigm for HIV-1, as they have the
      potential for sustained viral inhibition and reduced treatment interventions. One
      new method amendable to a gene-based therapy is the clustered regularly
      interspaced short palindromic repeats (CRISPR)-associated protein-9 nuclease
      (Cas9) gene editing system. AREAS COVERED: CRISPR/Cas9 can be engineered to
      successfully modulate an array of disease-causing genetic elements. We discuss
      the diverse roles that CRISPR/Cas9 may play in targeting HIV and eradicating
      infection. The Cas9 nuclease coupled with one or more small guide RNAs can target
      the provirus to mediate excision of the integrated viral genome. Moreover, a
      modified nuclease-deficient Cas9 fused to transcription activation domains may
      induce targeted activation of proviral gene expression allowing for the purging
      of the latent reservoirs. These technologies can also be exploited to target host
      dependency factors such as the co-receptor CCR5, thus preventing cellular entry
      of the virus. EXPERT OPINION: The diversity of the CRISPR/Cas9 technologies
      offers great promise for targeting different stages of the viral life cycle, and
      have the capacity for mediating an effective and sustained genetic therapy
      against HIV.

PMID- 25865335
TI  - Experimental system to detect a labeled cell monolayer in a microfluidic
      environment.
AB  - PURPOSE: To investigate the feasibility of detecting a living cell monolayer
      labeled with gadoterate (Gd-DOTA) in a microfluidic environment, by micromagnetic
      resonance imaging (MRI) in a 2.35T small-animal system. The development of new
      targeted contrast agents (CAs) requires proof-of-concept studies in order to
      establish the detectability of the CA and to predict the role of biodistribution
      in its uptake mechanisms. A promising approach is to carefully mimic the in vivo
      pharmacokinetic context with reduced experimental complexity compared to in vivo
      situations. MATERIALS AND METHODS: A dedicated experimental system was built by
      combining a microfluidic slide and a radiofrequency probe based on a 6 mm
      diameter multiturn transmission-line resonator. Adherent KB cells were incubated
      with different concentrations of Gd. MRI data were acquired at 2.35T with a 3D
      gradient echo and a resolution of 12.4 MUm perpendicular to the cell layer. The
      longitudinal relaxation rate, R1 , was measured as a function of the amount of Gd
      internalized by the cells. RESULTS: R1 measurements for different Gd
      concentrations per cell were performed using data with an signal-to-noise ratio
      (SNR) of 100. Relaxation-rate variations DeltaR1 of 0.035 s(-1) were measured. A
      quenching effect was observed at Gd concentrations above 20 fmol/cell.
      CONCLUSION: Our results suggest that this dedicated experimental system is
      suitable for specifically assessing new high-relaxivity targeted CAs under real
      time uptake conditions.

PMID- 25865336
TI  - Impact of high lipoprotein(a) levels on in-stent restenosis and long-term
      clinical outcomes of angina pectoris patients undergoing percutaneous coronary
      intervention with drug-eluting stents in Asian population.
AB  - Lipoprotein(a) (Lp(a)) is known to be associated with cardiovascular
      complications and atherothrombotic properties in general populations. However, it
      has not been examined whether Lp(a) levels are able to predict adverse
      cardiovascular outcomes in patients undergoing percutaneous coronary intervention
      (PCI) with drug-eluting stents (DES). A total of 595 consecutive patients with
      angina pectoris who underwent elective PCI with DES were enrolled from 2004 to
      2010. The patients were divided into two groups according to the levels of Lp(a):
      Lp(a) < 50 mg/dL (n = 485 patients), and Lp(a) >= 50 mg/dL (n = 111 patients).
      The 6-9-month angiographic outcomes and 3-year cumulative major clinical outcomes
      were compared between the two groups. Binary restenosis occurred in 26 of 133
      lesions (19.8%) in the high Lp(a) group and 43 of 550 lesions (7.9%) in the low
      Lp(a) group (P = 0.001). In multivariate analysis, the reference vessel diameter,
      low density lipoprotein cholesterol, total lesion length, and Lp(a) >= 50 mg/dL
      were predictors of binary restenosis. In the Cox proportional hazards regression
      analysis, Lp(a) > 50 mg/dL was significantly associated with the 3-year adverse
      clinical outcomes including any myocardial infarction, revascularization (target
      lesion revascularization (TLR) and target vessel revascularization (TVR)), TLR
      major adverse cardiac events (MACEs), TVR-MACE, and All-MACEs. In our study, high
      Lp(a) level >= 50 mg/dL in angina pectoris patients undergoing elective PCI with
      DES was significantly associated with binary restenosis and 3-year adverse
      clinical outcomes in an Asian population.

PMID- 25865338
TI  - Simulating yield response of rice to salinity stress with the AquaCrop model.
AB  - The FAO AquaCrop model has been widely applied throughout the world to simulate
      crop responses to deficit water applications. However, its application to saline
      conditions is not yet reported, though saline soils are common in coastal areas.
      In this study, we parameterized and tested AquaCrop to simulate rice yield under
      different salinity regimes. The data and information required in the model were
      collected through a field experiment at the Bangladesh Agricultural Research
      Institute, Gazipur. The experiment was conducted with the BRRI Dhan28, a popular
      boro rice variety in Bangladesh, with five levels of saline water irrigation,
      three replicates for each level. In addition, field monitoring was carried out at
      Satkhira in the southwest coastal region of Bangladesh to collect data and
      information based on farmers' practices and to further validate the model. The
      results indicated that the AquaCrop model with most of its default parameters
      could replicate the variation of rice yield with the variation of salinity
      reasonably well. The root mean square error and mean absolute error of the model
      yield were only 0.12 t per ha and 0.03 t per ha, respectively. The crop response
      versus soil salinity stress curve was found to be convex in shape with a lower
      threshold of 2 dS m(-1), an upper threshold of 10 dS m(-1) and a shape factor of
      2.4. As the crop production system in the coastal belt of Bangladesh has become
      vulnerable to climate induced sea-level rise and the consequent increase in water
      and soil salinity, the AquaCrop would be a useful tool in assessing the potential
      impact of these future changes as well as other climatic parameters on rice yield
      in the coastal region. 

PMID- 25865337
TI  - Novel fast adapting interneurons mediate cholinergic-induced fast GABAA
      inhibitory postsynaptic currents in striatal spiny neurons.
AB  - Previous work suggests that neostriatal cholinergic interneurons control the
      activity of several classes of GABAergic interneurons through fast nicotinic
      receptor-mediated synaptic inputs. Although indirect evidence has suggested the
      existence of several classes of interneurons controlled by this mechanism, only
      one such cell type, the neuropeptide-Y-expressing neurogliaform neuron, has been
      identified to date. Here we tested the hypothesis that in addition to the
      neurogliaform neurons that elicit slow GABAergic inhibitory responses, another
      interneuron type exists in the striatum that receives strong nicotinic
      cholinergic input and elicits conventional fast GABAergic synaptic responses in
      projection neurons. We obtained in vitro slice recordings from double transgenic
      mice in which Channelrhodopsin-2 was natively expressed in cholinergic neurons
      and a population of serotonin receptor-3a-Cre-expressing GABAergic interneurons
      were visualized with tdTomato. We show that among the targeted GABAergic
      interneurons a novel type of interneuron, termed the fast-adapting interneuron,
      can be identified that is distinct from previously known interneurons based on
      immunocytochemical and electrophysiological criteria. We show using optogenetic
      activation of cholinergic inputs that fast-adapting interneurons receive a
      powerful supra-threshold nicotinic cholinergic input in vitro. Moreover, fast
      adapting neurons are densely connected to projection neurons and elicit fast,
      GABAA receptor-mediated inhibitory postsynaptic current responses. The nicotinic
      receptor-mediated activation of fast-adapting interneurons may constitute an
      important mechanism through which cholinergic interneurons control the activity
      of projection neurons and perhaps the plasticity of their synaptic inputs when
      animals encounter reinforcing or otherwise salient stimuli. 

PMID- 25865339
TI  - Reply: To PMID 25103986.

PMID- 25865340
TI  - More than a decade after live donor nephrectomy: a prospective cohort study.
AB  - Previously reported short-term results after live kidney donation show no
      negative consequences for the donor. The incidence of new-onset morbidity takes
      years to emerge, making it highly likely that this will be missed during short
      term follow-up. Therefore, evidence on long-term outcome is essential. A 10-year
      follow-up on renal function, hypertension, quality of life (QOL), fatigue, and
      survival was performed of a prospective cohort of 100 donors. After a median
      follow-up time of 10 years, clinical data were available for 97 donors and QOL
      data for 74 donors. Nine donors died during follow-up of unrelated causes to
      donation, and one donor was lost to follow-up. There was a significant decrease
      in kidney function of 12.9 ml/min (P < 0.001) at follow-up. QOL showed
      significant clinically relevant decreases of 10-year follow-up scores in SF-36
      dimensions of physical function (P < 0.001), bodily pain (P = 0.001), and general
      health (P < 0.001). MFI-20 scores were significantly higher for general fatigue
      (P < 0.001), physical fatigue (P < 0.001), reduced activity (P = 0.019), and
      reduced motivation (P = 0.030). New-onset hypertension was present in 25.6% of
      the donors. Donor outcomes are excellent 10 years post-donation. Kidney function
      appears stable, and hypertension does not seem to occur more frequently compared
      to the general population. 

PMID- 25865341
TI  - The World Hypertension League challenges hypertension and cardiovascular
      organizations to develop strategic plans for the prevention and control of
      hypertension.

PMID- 25865342
TI  - Dual enhancement of light extraction efficiency of flip-chip light-emitting
      diodes with multiple beveled SiC surface and porous ZnO nanoparticle layer
      coating.
AB  - A porous ZnO nanoparticle layer coating composed of columnar ZnO nanoparticle
      piles and a multiple-beveled substrate was used to enhance the light extraction
      efficiency of GaN-based flip-chip light-emitting diodes (FC-LEDs), which were
      grown on high-purity SiC substrates. The SiC substrate was multiple-beveled by
      fabricating an 'X' pattern on the face of it, followed by a deposition of a
      porous ZnO nanoparticle layer on the 'X'-patterned surface. A porous ZnO
      nanoparticle layer was fabricated with gas phase cluster beam deposition in a
      glancing incidence. The incident angular-resolved light transmission of the ZnO
      nanostructure beyond the critical angle of total internal reflection (TIR) was
      greatly enhanced. The light output power of the LED was improved by nearly 60%
      compared to the original planar GaN-based LED on an SiC substrate (FC-SLED),
      which contained a significant enhancement supplemental to the 18%
      electroluminescence (EL) enhancement realized with the 'X'-pattern beveling. We
      demonstrated that a dual enhancement of light extraction efficiency was achieved
      by using the hierarchical surface consisting of microscale textures (the multiple
      beveled surfaces) and nanoscale structures (the ZnO nanoparticle layers). 

PMID- 25865343
TI  - Preparation of Nd-Fe-B by nitrate-citrate auto-combustion followed by the
      reduction-diffusion process.
AB  - The Nd2Fe14B alloy has been successfully synthesized by nitrate-citrate auto
      combustion followed by the reduction and diffusion process with low energy
      consumption. H3BO3, Fe(NO3)3.9H2O, and Nd(NO3)3.6H2O were used as precursors and
      citric acid was used as the chelating ligand of metal ions. Ammonia water was
      used to adjust pH to 7. CaH2 was used as a reducing agent for the reduction and
      diffusion process. NdFeO3 and Fe2O3 were produced during auto-combustion of gel.
      The combustion process of the gel was investigated by TGA/DTA curve measurements.
      The phase compositions were studied by XRD measurements. The differences of the
      overall morphology and magnetic properties were measured by SEM, TEM and
      vibrating sample magnetometry (VSM) at 300 K. The comparison of the magnetic
      properties of the reduced samples between the pellet type and the random powder
      type was done with VSM and it showed better magnetic properties of the pellet
      type Nd2Fe14B. Making a compact pellet type sample for reduction is more
      efficient for solid reduction and phase transition for higher coercivity. 

PMID- 25865344
TI  - Bioremediation efficiency of the largest scale artificial Porphyra yezoensis
      cultivation in the open sea in China.
AB  - The bioremediation efficiency of China's largest scale Porphyra yezoensis
      cultivation for removing dissolved nutrients and controlling harmful algae was
      studied in the radial sandbanks waters of Jiangsu Province in the year 2012-2013.
      Mean nutrient concentration values in the P. yezoensis cultivation area were
      significantly lower than those in the non-cultivation area, especially during the
      cultivation season (p<0.05). Tissue nitrogen and phosphorus contents of seaweeds
      were 5.99-0.80% (dry weight (DW)) and 0.16-0.19% (DW), respectively. Production
      of P. yezoensis was 58950.87tons DW. Based on these values, 3688.15tons of tissue
      nitrogen and 105.61tons of tissue phosphorus were removed by harvesting P.
      yezoensis. The richness index of the red tide species Skeleton emacostatum
      declined from 0.32 to 0.05 during the P. yezoensis cultivation season. These
      results indicate that large-scale cultivation of P. yezoensis can be used to
      efficiently alleviate eutrophication and control harmful algae blooms in open
      sea. 

PMID- 25865345
TI  - Effects of causeway construction on environment and biota of subtropical tidal
      flats in Okinawa, Japan.
AB  - Okinawa, Japan is known for its high marine biodiversity, yet little work has
      been performed on examining impacts of numerous large-scale coastal development
      projects on its marine ecosystems. Here, we examine apparent impacts of the
      construction of the Kaichu-Doro causeway, which was built over 40 years ago. The
      causeway is a 4.75 km long embankment that divides a large tidal flat and has
      only two points of water exchange along its entire length. We employed quadrats,
      transects, sampling, visual surveys, and microbial community analyses combined
      with environmental, water quality data, and 1m cores, at five stations of two
      paired sites each (one on each side of Kaichu-Doro) to investigate how the
      environment and biota have changed since the Kaichu-Doro was built. Results
      indicate reduction in water flow, and site S1 was particularly heavily impacted
      by poor water quality, with low diversity and disturbed biotic communities.

PMID- 25865346
TI  - Integrated use of biomarkers and condition indices in mussels (Mytilus
      galloprovincialis) for monitoring pollution and development of biomarker index to
      assess the potential toxic of coastal sites.
AB  - In this study, we are interested in spatial and temporal variations of the
      biological and physiological responses of mussels collected from contrasting
      marine sites regarding their levels of pollution. We measured both the conditions
      indices and the enzymatic biomarker expression: acetylcholinesterase (AChE),
      catalase (CAT) and glutathione S-transferase (GST) activity. The enzymatic
      biomarkers were chosen because they respond to environmental stress. Results show
      a significant interactions between biomarker variations and conditions indices in
      the industrial harbor site throughout the seasons. But no significant changes in
      the reference site. Furthermore, we classified the sites along the seasons
      according to their potential ecotoxicity, calculated based on the sum of the
      normalised values of the biomarkers. The results show a very high biomarker index
      in the impacted site with irregular changes between seasons. This biomarker index
      is therefore a valuable tool that could be used to classify the toxic potential
      of coastal sites. 

PMID- 25865347
TI  - Activation of Galphai at the Golgi by GIV/Girdin imposes finiteness in Arf1
      signaling.
AB  - A long-held tenet of heterotrimeric G protein signal transduction is that it is
      triggered by G protein-coupled receptors (GPCRs) at the PM. Here, we demonstrate
      that Gi is activated in the Golgi by GIV/Girdin, a non-receptor guanine
      nucleotide exchange factor (GEF). GIV-dependent activation of Gi at the Golgi
      maintains the finiteness of the cyclical activation of ADP-ribosylation factor 1
      (Arf1), a fundamental step in vesicle traffic in all eukaryotes. Several
      interactions with other major components of Golgi trafficking-e.g., active Arf1,
      its regulator, ArfGAP2/3, and the adaptor protein beta-COP-enable GIV to
      coordinately regulate Arf1 signaling. When the GIV-Galphai pathway is selectively
      inhibited, levels of GTP-bound Arf1 are elevated and protein transport along the
      secretory pathway is delayed. These findings define a paradigm in non-canonical G
      protein signaling at the Golgi, which places GIV-GEF at the crossroads between
      signals gated by the trimeric G proteins and the Arf family of monomeric GTPases.

PMID- 25865348
TI  - BMP-SHH signaling network controls epithelial stem cell fate via regulation of
      its niche in the developing tooth.
AB  - During embryogenesis, ectodermal stem cells adopt different fates and form
      diverse ectodermal organs, such as teeth, hair follicles, mammary glands, and
      salivary glands. Interestingly, these ectodermal organs differ in their tissue
      homeostasis, which leads to differential abilities for continuous growth
      postnatally. Mouse molars lose the ability to grow continuously, whereas incisors
      retain this ability. In this study, we found that a BMP-Smad4-SHH-Gli1 signaling
      network may provide a niche supporting transient Sox2+ dental epithelial stem
      cells in mouse molars. This mechanism also plays a role in continuously growing
      mouse incisors. The differential fate of epithelial stem cells in mouse molars
      and incisors is controlled by this BMP/SHH signaling network, which partially
      accounts for the different postnatal growth potential of molars and incisors.
      Collectively, our study highlights the importance of crosstalk between two
      signaling pathways, BMP and SHH, in regulating the fate of epithelial stem cells
      during organogenesis.

PMID- 25865349
TI  - Quantitative characterization of metacarpal and radial bone in rheumatoid
      arthritis using high resolution- peripheral quantitative computed tomography.
AB  - AIM: The objectives of this study were: (i) to develop a standardized method of
      quantifying bone mineral density (BMD) and microarchitecture in the hand and
      wrist bones of patients with rheumatoid arthritis (RA) using high resolution-
      peripheral quantitative computed tomography (HR-pQCT); (ii) to compare
      quantitative bone parameters between RA and post-menopausal osteopenic (PM-OP)
      subjects; and (iii) to correlate quantitative bone parameters at the distal
      radius with those at the metacarpal heads in RA subjects. METHODS: HR-pQCT
      imaging of the dominant hand and wrist was performed in 12 female RA patients.
      BMD and trabecular parameters for the 2-12% head region of the second and third
      metacarpals were calculated and compared between RA patients and healthy
      controls. Bone parameters were also calculated for 110 slices of the distal
      radius in RA patients and compared to data from controls and PM-OP women from a
      previous study. RESULTS: Compared to controls, RA patients had significantly
      decreased BMD, trabecular volume and number, and increased trabecular
      heterogeneity in the third metacarpal and distal radius. Significantly lower
      trabecular number and significantly higher ratio of outer annular trabecular BMD
      to inner trabecular BMD were observed in patients with RA, compared to patients
      with osteopenia (P < 0.05). Trabecular BMD in the third metacarpal and in the
      distal radius were significantly correlated (rho = 0.918, P < 0.0001) in RA
      patients. CONCLUSION: This study established a standardized method for
      quantifying bone density and trabecular properties in the hand and wrist bones of
      RA patients using HR-pQCT. Deterioration of bone structure in RA patients was
      found comparable to that in osteopenic women, and trabecular bone loss near
      affected joints was found to be correlated with bone loss away from joints.

PMID- 25865350
TI  - Two-year prospective evaluation of colonization with extended-spectrum beta
      lactamase-producing Enterobacteriaceae: time course and risk factors.
AB  - BACKGROUND: We wanted to determine the time course of colonization with extended
      spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae (EPE), sites of
      colonization and risk factors for prolonged colonization with EPE to obtain
      information for successful infection control measures. METHODS: Rectal swab,
      urine, throat swab and other clinically relevant samples (wound swab, tracheal
      aspirate and sputum) were obtained from each participant. Sets of follow-up
      samples and data about potential risk factors for prolonged colonization with EPE
      were collected every 3 months for 2 years. Multivariate analysis using a logistic
      regression model was performed to identify risk factors for prolonged
      colonization. RESULTS: A total of 114 patients were included in the study, 49
      completed the 2-year follow-up. In all, 611 sample sets were collected, 309
      (50.6%) of which were positive for ESBL. Of the positive sample sets, 90% had a
      rectal swab positive for ESBL, the throat swab was positive for ESBL in 17.2% of
      cases and urine in 36.2% of cases; 10% of positive sample sets had negative
      rectal swabs with EPE isolated from other sites, most often from urine.
      Immobility was found to be associated with prolonged carriage (>= 12 months) of
      EPE. After 2 years, 15/49 (30.6%) patients were colonized with EPE. In 12/49
      (24.5%) patients, transient negativity was observed. CONCLUSIONS: We found that
      prolonged colonization with EPE was common, especially in bedridden patients.
      Transient negative samples were often observed during the course of colonization.
      In some patients, urine can be the only positive site from which EPE are
      isolated.

PMID- 25865351
TI  - Dectin-1 activation unlocks IL12A expression and reveals the TH1 potency of
      neonatal dendritic cells.
AB  - BACKGROUND: Early life is characterized by a high susceptibility to infection and
      a TH2-biased CD4 T-cell response to vaccines. Toll-like receptor (TLR) agonists
      are currently being implemented as new vaccine adjuvants for TH1 activation, but
      their translation to the field of pediatric vaccines is facing the impairment of
      neonatal innate TLR responses. OBJECTIVE: We sought to analyze C-type lectin
      receptor pathways as an alternative or a coactivator to TLRs for neonatal
      dendritic cell activation for TH1 polarization. METHODS: Neonatal monocyte
      derived dendritic cells (moDCs) were exposed to various combinations of TLR
      agonists with or without Dectin-1 agonist. IL-12 and IL-23 responses were
      analyzed at the transcriptional and protein levels after stimulation. The
      intracellular pathways triggered by combined TLR plus Dectin-1 stimulation was
      determined by using pharmacologic inhibitors. The capacity of neonatal moDCs to
      differentiate naive CD4 TH cells was evaluated in cocultures with heterologous
      neonatal naive T cells. Curdlan was finally tested as an adjuvant within a
      subunit tuberculosis vaccine in neonatal mice. RESULTS: Simultaneous coactivation
      through Dectin-1 and TLRs induced robust secretion of IL-12p70 by neonatal moDCs
      by unlocking transcriptional control on the p35 subunit of IL-12. Both the spleen
      tyrosine kinase and Raf-1 pathways were involved in this process, allowing
      differentiation of neonatal naive T cells toward IFN-gamma-producing TH1 cells.
      In vivo a Dectin-1 agonist as adjuvant was sufficient to induce TH1 responses
      after vaccination of neonatal mice. CONCLUSION: Coactivation of neonatal moDCs
      through Dectin-1 allows TLR-mediated IL-12p70 secretion and TH1 polarization of
      neonatal T cells. Dectin-1 agonists represent a promising TH1 adjuvant for
      pediatric vaccination.

PMID- 25865352
TI  - A genome-wide association study reveals 2 new susceptibility loci for atopic
      dermatitis.

PMID- 25865353
TI  - Identification of the cysteine protease Amb a 11 as a novel major allergen from
      short ragweed.
AB  - BACKGROUND: Allergy to pollen from short ragweed (Ambrosia artemisiifolia) is a
      serious and expanding health problem in the United States and in Europe.
      OBJECTIVE: We sought to investigate the presence of undescribed allergens in
      ragweed pollen. METHODS: Ragweed pollen proteins were submitted to high
      resolution gel electrophoresis and tested for IgE reactivity by using sera from
      92 American or European donors with ragweed allergy. Pollen transcriptome
      sequencing, mass spectrometry (MS), and recombinant DNA technologies were applied
      to characterize new IgE-binding proteins. RESULTS: High-resolution IgE
      immunoblotting experiments revealed that 50 (54%) of 92 patients with ragweed
      allergy were sensitized to a 37-kDa allergen distinct from Amb a 1. The full
      length cDNA sequence for this molecule was obtained by means of PCR cloning after
      MS sequencing of the protein combined with ragweed pollen RNA sequencing. The
      purified allergen, termed Amb a 11, was fully characterized by MS and confirmed
      to react with IgEs from 66% of patients. This molecule is a 262-amino-acid thiol
      protease of the papain family expressed as a combination of isoforms and
      glycoforms after proteolytic removal of N- and C-terminal propeptides from a
      proform. Three-dimensional modeling revealed a high structural homology with
      known cysteine proteases, including the mite Der p 1 allergen. The protease
      activity of Amb a 11, as well as its capacity to activate basophils from patients
      with ragweed allergy, were confirmed. The production of a nonglycosylated
      recombinant form of Amb a 11 in Escherichia coli established that glycosylation
      is not required for IgE binding. CONCLUSION: We identified the cysteine protease
      Amb a 11 as a new major allergen from ragweed pollen. Given the similar
      physicochemical properties shared by the 2 major allergens, we hypothesize that
      part of the allergenic activity previously ascribed to Amb a 1 is rather borne by
      Amb a 11.

PMID- 25865354
TI  - MED12 exon 2 mutations in phyllodes tumors of the breast.
AB  - Exon 2 of MED12, a subunit of the transcriptional mediator complex, has been
      frequently mutated in uterine leiomyomas and breast fibroadenomas; however, it
      has been rarely mutated in other tumors. Although the mutations were also found
      in uterine leiomyosarcomas, the frequency was significantly lower than in uterine
      leiomyomas. Here, we examined the MED12 mutation in phyllodes tumors, another
      biphasic tumor with epithelial and stromal components related to breast
      fibroadenomas. Mutations in MED12 exon 2 were analyzed in nine fibroadenomas and
      eleven phyllodes tumors via Sanger sequencing. A panel of cancer- and sarcoma
      related genes was also analyzed using Ion Torrent next-generation sequencing. Six
      mutations in fibroadenomas, including those previously reported (6/9, 67%), and
      five mutations in phyllodes tumors (5/11, 45%) were observed. Three mutations in
      the phyllodes tumors were missense mutations at Gly44, which is common in uterine
      leiomyomas and breast fibroadenomas. In addition, two deletion mutations (in
      frame c.133_144del12 and loss of splice acceptor c.100-68_137del106) were
      observed in the phyllodes tumors. No other recurrent mutation was observed with
      next-generation sequencing. Frequent mutations in MED12 exon 2 in the phyllodes
      tumors suggest that it may share genetic etiology with uterine leiomyoma, a
      subgroup of uterine leiomyosarcomas and breast fibroadenoma. 

PMID- 25865355
TI  - The clinical implications of thalidomide in inflammatory bowel diseases.
AB  - Thalidomide has anti-inflammatory and anti-angiogenetic activity that makes it
      suitable for treating inflammatory bowel diseases (IBD). The recent guidelines
      from the European Crohn's and Colitis Organization/European Society for Pediatric
      Gastroenterology Hepatology and Nutrition conclude that thalidomide cannot be
      recommended in refractory pediatric Crohn's disease but that it may be considered
      in selected cohorts of patients who are not anti-TNFalpha agent responders. The
      main adverse effect is the potential teratogenicity that renders the long-term
      use of thalidomide problematic in young adults due to the strict need for
      contraceptive use. In short-term use it is relatively safe; the most likely
      adverse effect is the neuropathy, which is highly reversible in children. So far
      the use of thalidomide is reported in 223 adult and pediatric IBD patients (206
      with Crohn's disease). In the following sections, the authors will discuss
      efficacy and safety of thalidomide, in the short-term treatment of IBD. 

PMID- 25865357
TI  - Intrinsic Connectivity Networks in post-traumatic stress disorder during sub- and
      supraliminal processing of threat-related stimuli.
AB  - OBJECTIVE: To investigate the functional connectivity of large-scale intrinsic
      connectivity networks (ICNs) in post-traumatic stress disorder (PTSD) during
      subliminal and supraliminal presentation of threat-related stimuli. METHOD: Group
      independent component analysis was utilized to study functional connectivity
      within the ICNs most correlated with the Default-mode Network (DMN), Salience
      Network (SN), and Central Executive Network (CEN) in PTSD participants (n = 26)
      as compared to healthy controls (n = 20) during sub- and supraliminal processing
      of threat-related stimuli. RESULTS: Comparing patients with PTSD with healthy
      participants, prefrontal and anterior cingulate cortex involved in top-down
      regulation showed increased integration during subliminal threat processing
      within the CEN and SN and during supraliminal threat processing within the DMN.
      The right amygdala showed increased connectivity with the DMN during subliminal
      processing in PTSD as compared to controls. Brain regions associated with self
      awareness and consciousness exhibited decreased connectivity during subliminal
      threat processing in PTSD as compared to controls: the claustrum within the SN
      and the precuneus within the DMN. CONCLUSION: Key nodes of the ICNs showed
      altered functional connectivity in PTSD as compared to controls, and differential
      results characterized sub- and supraliminal processing of threat-related stimuli.
      These findings enhance our understanding of ICNs underlying PTSD at different
      levels of conscious threat perception.

PMID- 25865356
TI  - Plasticity of Hopx(+) type I alveolar cells to regenerate type II cells in the
      lung.
AB  - The plasticity of differentiated cells in adult tissues undergoing repair is an
      area of intense research. Pulmonary alveolar type II cells produce surfactant and
      function as progenitors in the adult, demonstrating both self-renewal and
      differentiation into gas exchanging type I cells. In vivo, type I cells are
      thought to be terminally differentiated and their ability to give rise to
      alternate lineages has not been reported. Here we show that Hopx becomes
      restricted to type I cells during development. However, unexpectedly, lineage
      labelled Hopx(+) cells both proliferate and generate type II cells during adult
      alveolar regrowth following partial pneumonectomy. In clonal 3D culture, single
      Hopx(+) type I cells generate organoids composed of type I and type II cells, a
      process modulated by TGFbeta signalling. These findings demonstrate unanticipated
      plasticity of type I cells and a bidirectional lineage relationship between
      distinct differentiated alveolar epithelial cell types in vivo and in single-cell
      culture. 

PMID- 25865358
TI  - The various hemodynamic profiles of the patent ductus arteriosus in adults.
AB  - The patent ductus arteriosus (PDA) has diverse clinical and hemodynamic
      manifestations depending on its size and the degree of the ensuing left-to-right
      shunt. A small PDA that causes minor shunting has no major hemodynamic
      consequences. Conversely, a large PDA with a significant left-to-right shunt may
      lead to various hemodynamic abnormalities. These include left-sided volume
      overload that may result in heart failure and/or pulmonary hypertension, the
      latter being a flow-dependent and mostly reversible phenomenon. The most feared
      complication is the development of severe and irreversible pulmonary hypertension
      (Eisenmenger physiology). In this manuscript, we provide examples of the various
      hemodynamic profiles of PDA as assessed by echocardiography in the adult
      population. 

PMID- 25865360
TI  - Common dab, Limanda limanda (L.), as a natural carrier of salmonid alphavirus
      (SAV) from waters off north-west Ireland.

PMID- 25865359
TI  - Inhibitors of the apurinic/apyrimidinic endonuclease 1 (APE1)/nucleophosmin
      (NPM1) interaction that display anti-tumor properties.
AB  - The apurinic/apyrimidinic endonuclease 1 (APE1) is a protein central to the base
      excision DNA repair pathway and operates in the modulation of gene expression
      through redox-dependent and independent mechanisms. Aberrant expression and
      localization of APE1 in tumors are recurrent hallmarks of aggressiveness and
      resistance to therapy. We identified and characterized the molecular association
      between APE1 and nucleophosmin (NPM1), a multifunctional protein involved in the
      preservation of genome stability and rRNA maturation. This protein-protein
      interaction modulates subcellular localization and endonuclease activity of APE1.
      Moreover, we reported a correlation between APE1 and NPM1 expression levels in
      ovarian cancer, with NPM1 overexpression being a marker of poor prognosis. These
      observations suggest that tumors that display an augmented APE1/NPM1 association
      may exhibit increased aggressiveness and resistance. Therefore, targeting the
      APE1/NPM1 interaction might represent an innovative strategy for the development
      of anticancer drugs, as tumor cells relying on higher levels of APE1 and NPM1 for
      proliferation and survival may be more sensitive than untransformed cells. We set
      up a chemiluminescence-based high-throughput screening assay in order to find
      small molecules able to interfere with the APE1/NPM1 interaction. This screening
      led to the identification of a set of bioactive compounds that impair the
      APE1/NPM1 association in living cells. Interestingly, some of these molecules
      display anti-proliferative activity and sensitize cells to therapeutically
      relevant genotoxins. Given the prognostic significance of APE1 and NPM1, these
      compounds might prove effective in the treatment of tumors that show abundant
      levels of both proteins, such as ovarian or hepatic carcinomas.

PMID- 25865361
TI  - Co-assembly in chitosan-surfactant mixtures: thermodynamics, structures,
      interfacial properties and applications.
AB  - In this review, different aspects characterizing chitosan-surfactant mixtures are
      summarized and compared. Chitosan is a bioderived cationic polysaccharide that
      finds wide-ranged applications in various field, e.g., medical or food industry,
      in which synergistic effects with surfactant can play a fundamental role. In
      particular, the behavior of chitosan interacting with strong and weak anionic,
      nonionic as well as cationic surfactants is reviewed. We put a focus on
      oppositely charged systems, as they exhibit the most interesting features. In
      that context, we discuss the thermodynamic description of the interaction and in
      particular the structural changes as they occur as a function of the mixed
      systems and external parameters. Moreover, peculiar properties of chitosan coated
      phospholipid vesicles are summarized. Finally, their co-assembly at interfaces is
      briefly reviewed. Despite the behavior of the mentioned systems might strongly
      differ, resulting in a high variety of properties, few general rules can be
      pointed out which improve the understanding of such complex systems. 

PMID- 25865362
TI  - Frequency and specificity of red cell antibodies in thalassemia patients in
      Albania.
AB  - INTRODUCTION: Thalassemia major is a common hemoglobinopathy in Albania. However,
      there are no data available on the frequency of RBC alloimmunization and
      autoimmunization in transfusion-dependent Albanian patients with thalassemia.
      METHODS: A total of 118 patients with thalassemia receiving regular transfusions
      were studied during 5 years with antibody screening. During this period, they
      were exclusively transfused with blood matched for ABO, Rhesus and Kell system.
      These patients were previously exposed to unmatched blood because of blood
      shortages. RESULTS: Fourteen of 118 (11, 8%) patients developed alloantibodies.
      Twelve (10, 1%) were already present at the start of the study. Only 2 (1, 7%)
      were formed after the application of a strict Rh and Kell matching policy. The
      most common antibody was anti-K, followed by anti-D, anti-C, anti-E, anti-c, anti
      e, anti-Jk(b) , and anti-C(w) . Three patients developed anti-D plus anti-C. Anti
      K was combined with Rh antibodies in two of five cases. Anti-c was combined with
      anti-E in two of three cases. The majority of antibodies (10/14) belonged to the
      Rh blood group system. With the exception of the anti-Jk(b) and the anti-C(w) ,
      all antibodies were already present at the beginning of the follow-up period.
      During our follow-up, 27 patients (22.8%) developed autoantibodies. A strong
      coincidence was found between the presence of alloantibodies and autoantibodies.
      Eleven of 14 (78%) of the patients with alloantibodies had also autoantibodies,
      whereas autoantibodies were found in 16 of 104 (15%) of patients with thalassemia
      without autoantibodies. The rate of alloantibody formation dropped from 10.1% to
      1.7% after application of a strict Rh and Kell matching policy. CONCLUSION: A
      policy of Rhesus and Kell matching without occasional exceptions greatly reduced
      the development of new alloantibodies and autoantibodies. Self-sufficiency
      through regular blood donation is necessary for the full implementation of an
      extended match policy and the prevention of antibody formation in our patients.

PMID- 25865363
TI  - A critical review on properties and applications of microbial l-asparaginases.
AB  - l-Asparaginase is one of the main drugs used in the treatment of acute
      lymphoblastic leukemia (ALL), a commonly diagnosed pediatric cancer. Although
      several microorganisms are found to produce l-asparaginase, only the purified
      enzymes from E. coli and Erwinia chrysanthemi are employed in the clinical and
      therapeutic applications in humans. However, their therapeutic response seldom
      occurs without some evidence of hypersensitivity and other toxic side effects. l
      Asparaginase is also of prospective use in food industry to reduce the formation
      of acrylamide in fried, roasted or baked food products. This review is an attempt
      to compile information on the properties of l-asparaginases obtained from
      different microorganisms. The complications involved with the therapeutic use of
      the currently available l-asparaginases, and the enzyme's potential application
      as a food processing aid to mitigate acrylamide formation have also been
      reviewed. Further, avenues for searching alternate sources of l-asparaginase have
      been discussed, highlighting the prospects of endophytic microorganisms as a
      possible source of l-asparaginases with varied biochemical and pharmacological
      properties. 

PMID- 25865364
TI  - Spinal neurofibromatosis and phenotypic heterogeneity in NF1.

PMID- 25865365
TI  - First- and second-trimester maternal serum markers of pre-eclampsia in twin
      pregnancy.
AB  - OBJECTIVE: To evaluate the distribution of first- and second-trimester maternal
      serum markers in twin pregnancy with and without pre-eclampsia. METHODS: One
      hundred and forty-four twin and 109 unaffected singleton pregnancies were
      recruited from the same institution. First- and second-trimester maternal blood
      samples were stored and measured retrospectively for serum placental growth
      factor (PlGF), pregnancy-associated plasma protein-A (PAPP-A), free beta-human
      chorionic gonadotropin (beta-hCG) and alpha-fetoprotein (AFP). All had
      measurement of first-trimester serum markers, and 167 (66%) had second-trimester
      tests. Values were expressed in multiples of the gestation-specific median (MoMs)
      in singletons, adjusted for maternal weight, as appropriate. RESULTS: Pre
      eclampsia was diagnosed in 12 (9.0%) twin pregnancies of 133 continuing beyond 22
      weeks. In unaffected twin pregnancies, all serum markers were statistically
      significantly increased (P < 0.0001), consistent with a doubling of
      concentration. Among twin pregnancies, those with pre-eclampsia had a
      significantly reduced median PlGF compared with surviving unaffected twin
      pregnancies (0.96 MoM vs 1.46 MoM; P < 0.0002, two-tailed), whilst median PAPP-A,
      which is known to be reduced in affected singleton pregnancies, was increased
      (3.91 MoM vs 2.43 MoM; P < 0.0005, two-tailed). The levels of free beta-hCG (P <
      0.02) and AFP (P < 0.05) were also significantly raised, but to a lesser extent
      than was the level of PAPP-A. Using a logistic regression algorithm based on
      first- and second-trimester PlGF and PAPP-A, together with previously published
      uterine artery Doppler and mean arterial pressure measurements in the same
      series, the predicted pre-eclampsia detection rate was 65% for a 10% false
      positive rate. CONCLUSIONS: In twin pregnancy, the predicted detection rate of
      pre-eclampsia using first- and second-trimester maternal serum and biophysical
      markers is good. In contrast to singleton pregnancy, PAPP-A levels are raised in
      the first trimester of twin pregnancies destined to develop pre-eclampsia and
      therefore a different prediction algorithm is needed. Copyright (c) 2015 ISUOG.
      Published by John Wiley & Sons Ltd.

PMID- 25865366
TI  - Green leaf volatiles: biosynthesis, biological functions and their applications
      in biotechnology.
AB  - Plants have evolved numerous constitutive and inducible defence mechanisms to
      cope with biotic and abiotic stresses. These stresses induce the expression of
      various genes to activate defence-related pathways that result in the release of
      defence chemicals. One of these defence mechanisms is the oxylipin pathway, which
      produces jasmonates, divinylethers and green leaf volatiles (GLVs) through the
      peroxidation of polyunsaturated fatty acids (PUFAs). GLVs have recently emerged
      as key players in plant defence, plant-plant interactions and plant-insect
      interactions. Some GLVs inhibit the growth and propagation of plant pathogens,
      including bacteria, viruses and fungi. In certain cases, GLVs released from
      plants under herbivore attack can serve as aerial messengers to neighbouring
      plants and to attract parasitic or parasitoid enemies of the herbivores. The
      plants that perceive these volatile signals are primed and can then adapt in
      preparation for the upcoming challenges. Due to their 'green note' odour, GLVs
      impart aromas and flavours to many natural foods, such as vegetables and fruits,
      and therefore, they can be exploited in industrial biotechnology. The aim of this
      study was to review the progress and recent developments in research on the
      oxylipin pathway, with a specific focus on the biosynthesis and biological
      functions of GLVs and their applications in industrial biotechnology. 

PMID- 25865367
TI  - Integration of genetic and physical maps of the Primula vulgaris S locus and
      localization by chromosome in situ hybridization.
AB  - Heteromorphic flower development in Primula is controlled by the S locus. The S
      locus genes, which control anther position, pistil length and pollen size in pin
      and thrum flowers, have not yet been characterized. We have integrated S-linked
      genes, marker sequences and mutant phenotypes to create a map of the P. vulgaris
      S locus region that will facilitate the identification of key S locus genes. We
      have generated, sequenced and annotated BAC sequences spanning the S locus, and
      identified its chromosomal location. We have employed a combination of classical
      genetics and three-point crosses with molecular genetic analysis of recombinants
      to generate the map. We have characterized this region by Illumina sequencing and
      bioinformatic analysis, together with chromosome in situ hybridization. We
      present an integrated genetic and physical map across the P. vulgaris S locus
      flanked by phenotypic and DNA sequence markers. BAC contigs encompass a 1.5-Mb
      genomic region with 1 Mb of sequence containing 82 S-linked genes anchored to
      overlapping BACs. The S locus is located close to the centromere of the largest
      metacentric chromosome pair. These data will facilitate the identification of the
      genes that orchestrate heterostyly in Primula and enable evolutionary analyses of
      the S locus.

PMID- 25865368
TI  - The infant nasopharyngeal microbiome impacts severity of lower respiratory
      infection and risk of asthma development.
AB  - The nasopharynx (NP) is a reservoir for microbes associated with acute
      respiratory infections (ARIs). Lung inflammation resulting from ARIs during
      infancy is linked to asthma development. We examined the NP microbiome during the
      critical first year of life in a prospective cohort of 234 children, capturing
      both the viral and bacterial communities and documenting all incidents of ARIs.
      Most infants were initially colonized with Staphylococcus or Corynebacterium
      before stable colonization with Alloiococcus or Moraxella. Transient incursions
      of Streptococcus, Moraxella, or Haemophilus marked virus-associated ARIs. Our
      data identify the NP microbiome as a determinant for infection spread to the
      lower airways, severity of accompanying inflammatory symptoms, and risk for
      future asthma development. Early asymptomatic colonization with Streptococcus was
      a strong asthma predictor, and antibiotic usage disrupted asymptomatic
      colonization patterns. In the absence of effective anti-viral therapies,
      targeting pathogenic bacteria within the NP microbiome could represent a
      prophylactic approach to asthma. 

PMID- 25865370
TI  - Decorin-expressing adenovirus decreases collagen synthesis and upregulates MMP
      expression in keloid fibroblasts and keloid spheroids.
AB  - Decorin is a natural transforming growth factor-beta1 (TGF-beta1) antagonist.
      Reduced decorin synthesis is associated with dermal scarring, and increased
      decorin expression appears to reduce scar tissue formation. To investigate the
      therapeutic potential of decorin for keloids, human dermal fibroblasts (HDFs) and
      keloid-derived fibroblasts (KFs) were transduced with decorin-expressing
      adenovirus (dE1-RGD/GFP/DCN), and we examined the therapeutic potential of
      decorin-expressing Ad for treating pathologic skin fibrosis. Decorin expression
      was examined by immunofluorescence assay on keloid tissues. HDFs and KFs were
      transduced with dE1-RGD/GFP/DCN or control virus, and protein levels of decorin,
      epidermal growth factor receptor (EGFR) and secreted TGF-beta1 were assessed by
      Western blotting and ELISA. And type I and III collagen, and matrix
      metalloproteinase-1 (MMP-1) and matrix metalloproteinase-3 (MMP-3) mRNA levels
      were measured by real-time RT-PCR. Additionally, we immunohistochemically
      investigated the expression levels of the major extracellular matrix (ECM)
      proteins in keloid spheroids transduced with dE1-RGD/GFP/DCN. Lower decorin
      expression was observed in the keloid region compared to adjacent normal tissues.
      After treatment with dE1-RGD/GFP/DCN, secreted TGF-beta1 and EGFR protein
      expressions were decreased in TGF-beta1-treated HDFs and KFs. Also, type I and
      III collagen mRNA levels were decreased, and the expression of MMP-1 and MMP-3
      mRNA was strongly upregulated. In addition, the expression of type I and III
      collagen, fibronectin and elastin was significantly reduced in dE1-RGD/GFP/DCN
      transduced keloid spheroids. These results support the utility of decorin
      expressing adenovirus to reduce collagen synthesis in KFs and keloid spheroid,
      which may be highly beneficial in treating keloids. 

PMID- 25865371
TI  - Cloning and Genomic Characterization of a Natural Insecticidal Peptide LaIT1 with
      Unique DDH Structural Fold.
AB  - Two native peptides with disulfide-directed hairpin (DDH) fold, LaIT1 and LITX,
      were recently isolated from scorpion venom, a development that offered insights
      into exploring the evolutionary linkage between DDH and inhibitor cystine knot
      (ICK) peptides. In this work, we isolated and identified the full-length cDNAs of
      LaTI1, a representative member with DDH fold, and further determined its complete
      gene structure. The precursor organization of LaIT1 is similar to that of ICK
      peptides. The LaIT1 gene contains four exons interrupted by three unique introns
      and differed from ICK peptides, suggesting divergent genomic organizations of DDH
      peptides and ICK peptides. Phylogenetic analysis further showed that the "simple"
      DDH peptide originates from the "complex" ICK peptide, rather than the reverse.
      To the best of our knowledge, this is the first report on the genomic
      organization of DDH-fold peptides, and it presents new evidence of an
      evolutionary linkage between ICK and DDH peptides. 

PMID- 25865369
TI  - Crosstalk between Microbiota-Derived Short-Chain Fatty Acids and Intestinal
      Epithelial HIF Augments Tissue Barrier Function.
AB  - Interactions between the microbiota and distal gut are fundamental determinants
      of human health. Such interactions are concentrated at the colonic mucosa and
      provide energy for the host epithelium through the production of the short-chain
      fatty acid butyrate. We sought to determine the role of epithelial butyrate
      metabolism in establishing the austere oxygenation profile of the distal gut.
      Bacteria-derived butyrate affects epithelial O2 consumption and results in
      stabilization of hypoxia-inducible factor (HIF), a transcription factor
      coordinating barrier protection. Antibiotic-mediated depletion of the microbiota
      reduces colonic butyrate and HIF expression, both of which are restored by
      butyrate supplementation. Additionally, germ-free mice exhibit diminished
      retention of O2-sensitive dyes and decreased stabilized HIF. Furthermore, the
      influences of butyrate are lost in cells lacking HIF, thus linking butyrate
      metabolism to stabilized HIF and barrier function. This work highlights a
      mechanism where host-microbe interactions augment barrier function in the distal
      gut. 

PMID- 25865373
TI  - Does accessibility to antiretroviral care improve after down-referral of patients
      from hospitals to health centres in rural South Africa?
AB  - We conducted an evaluation of healthcare accessibility among patients taking
      antiretroviral treatment (ART) after they were 'down-referred' from hospital
      based programmes to primary healthcare (PHC) centres in a rural South African
      setting. A cross-sectional design was used to study 109 PHC users compared to a
      randomly selected control group of 220 hospital-based users. Both groups were
      matched for a minimum duration on ART of six months. Using a comprehensive
      healthcare-accessibility framework, the participants were asked about
      availability, affordability and acceptability of their ART care in structured
      exit interviews that were linked to their ART-clinic record reviews. Unadjusted
      and adjusted regression models were used. Down-referral was associated with
      reduced transportation and meal costs (p = 0.001) and travel time to an ART
      facility (p =0.043). The down-referred users were less likely to complain of long
      queues (adjusted odds ratio [AOR] 0.06; 95% confidence interval [95% CI]: 0.01
      0.29), were more likely to feel respected by health providers (AOR 4.43; 95% CI:
      1.07-18.02), perceived lower stigma (AOR 0.25; 95% CI: 0.07-0.91), and showed a
      higher level of ART adherence (AOR 8.71; 95% CI: 1.16-65.22) than the hospital
      based users. However, the down-referred users preferred to consult with doctors
      rather than nurses (AOR 3.43; 95% CI: 1.22-9.55) and they were more likely to
      visit private physicians (AOR 7.09; 95% CI: 3.86-13.04) and practice self-care
      (AOR 4.91; 95% CI: 2.37-10.17), resulting in increased health-related expenditure
      (p = 0.001). Therefore, the results indicate both gains and losses in ART care
      for the patients, and suggest that down-referred patients save time and money,
      feel more respected, perceive lower stigma and show better adherence levels.
      However, unintended consequences include increased costs of using private
      physicians and self-care, highlighting the need to further promote the potential
      gains of down-referral interventions in resource-poor settings. 

PMID- 25865374
TI  - Factors associated with HIV infection among sexually experienced adolescents in
      Africa: a pooled data analysis.
AB  - The article examines the factors associated with HIV status among adolescents
      aged 15-19 years in 13 African countries: Cote d'Ivoire, Democratic Republic of
      Congo, Guinea, Kenya, Liberia, Mali, Malawi, Rwanda, Sierra Leone, Swaziland,
      Tanzania, Zambia and Zimbabwe. The data were derived from demographic and health
      surveys or AIDS indicator surveys conducted between 2004 and 2009. The levels of
      HIV prevalence among adolescents varied considerably across the countries. There
      was significantly higher HIV prevalence among female adolescents as compared with
      their male counterparts. For male adolescents, circumcision was the only variable
      significantly associated with HIV status. Nonetheless, the data suggest that the
      association between male circumcision and HIV status may be exaggerated. Indeed,
      regional-level random effects became insignificant once male circumcision was
      introduced into the estimated models, indicating a strong correlation between
      unmeasured regional-level factors and male circumcision. For female adolescents,
      multiple sexual partnerships, time elapsed since sexual debut, marital status,
      household wealth, and the regional prevalence of male circumcision were strongly
      and positively associated with HIV status. Moreover, for female adolescents there
      appear to be significant unmeasured variables operating at the regional level
      which influence the levels of HIV infection. The implications of the findings for
      HIV-prevention programming, policy and research are discussed. 

PMID- 25865375
TI  - Piloting antiretroviral treatment in South Africa: the role of partnerships in
      the Western Cape's provincial roll-out.
AB  - In 1999, the government of the Western Cape Province, South Africa, entered into
      a partnership with Medecins Sans Frontieres (MSF) to provide HIV treatment
      through public health clinics in the peri-urban settlement of Khayelitsha. From
      2000 onwards, this partnership ran South Africa's first antiretroviral treatment
      (ART) programme. Due to the province's limited experience (as of 1999) in
      implementing and monitoring an ART programme, and the National Department of
      Health's opposition to the public provision of ART, this partnership was
      instrumental in piloting and later scaling-up the Western Cape's ART programme.
      Numerous studies have documented this pilot ART programme from a health system or
      clinical perspective. This study instead used qualitative methods to examine the
      factors that facilitated the public provision of ART in the Western Cape. With
      reference to the role of partnerships in piloting new health interventions, the
      article explores the partnership that was established between the provincial
      government, civil society organisations, research institutes, and service
      providers to support the public provision of ART in Khayelitsha. This partnership
      has demonstrated that ART programmes can be implemented successfully within
      resource-constrained settings, achieving high levels of treatment adherence, low
      rates of loss to follow-up and excellent health outcomes. Lessons from the
      partnership's components and strategies are therefore of vital significance to
      realising the roll-out of ART programmes in various contexts across the
      developing world, demonstrating the crucial role of collaboration and integration
      in the establishment and maintenance of these programmes. 

PMID- 25865376
TI  - Fear appeals in HIV-prevention messages: young people's perceptions in northern
      Tanzania.
AB  - The aims of the study were to elicit the perceptions of young people in Tanzania
      on the role of fear appeals in HIV-prevention messages and to identify important
      contextual factors that may influence young people's perceptions of HIV
      prevention posters. A total of 10 focus groups were conducted to investigate the
      role of fear appeals using the extended parallel process model (EPPM) as a guide.
      Young people were shown a series of images (mostly posters) with alternating high
      and low-threat messages (fear appeals), and then asked questions about their
      overall beliefs about HIV and AIDS, as well as about their response in terms of
      perceived susceptibility to HIV infection, the severity of the message, and their
      perceptions of self-efficacy and response efficacy. The images and messages that
      specifically targeted young people were highest in inducing perceived
      susceptibility to HIV infection, while pictorial descriptions of the physical
      consequences of HIV infection and those messages related to the stigma and
      discrimination faced by HIV-infected or affected people induced greater
      perceptions of severity. The information-based posters rated high in inducing
      response efficacy, while none of the images seemed to convince young people that
      they had the self-efficacy to perform the recommended health behaviours. The
      young people expressed a preference for fear-based appeals and a belief that this
      could work well in HIV-prevention efforts, yet they also stated a desire for more
      information-based messages about how to protect themselves. Finally, the messages
      evoking the most emotional responses were those that had been locally conceived
      rather than ones developed by large-scale donor-funded campaigns. Finding the
      appropriate balance between fear and efficacy in HIV-prevention messages is
      imperative. Further research is needed to better understand how and when fear
      appeals work and do not work in African settings, especially among young people. 

PMID- 25865377
TI  - The ethical and legal regulation of HIV-vaccine research in Africa: lessons from
      Cameroon, Malawi, Nigeria, Rwanda and Zambia.
AB  - Ethical and legal frameworks are important for ensuring that the goals of
      scientific research are realised while at the same time the rights and welfare of
      human participants are adequately protected. A balance in attaining these two
      goals can be achieved if such frameworks provide for legally binding structures
      and processes to oversee, regulate, and monitor research on human participants
      according to accepted norms and standards. From 2007 to 2009, an ethical/legal
      audit, sponsored by the WHO/UNAIDS Ethics, Law and Human Rights Working Group of
      the African AIDS Vaccine Programme (AAVP ELH), was conducted in regard to five
      African countries (Cameroon, Malawi, Nigeria, Rwanda and Zambia) to determine
      whether these countries have adequate laws, ethical guidelines and policies in
      place to regulate HIV-vaccine research. This article discusses the findings of
      the audit with a view to highlighting key lessons that can be learnt from these
      countries. The article provides the context of the audit by highlighting its
      rationale, aims and methods. We discuss the general findings of the audit and the
      complex issues arising from HIV-vaccine research, specifically. Lastly, we
      propose specific ways in which the ethical/legal frameworks guiding research with
      human participants in these countries can be improved. 

PMID- 25865372
TI  - Temporal trends of time to antiretroviral treatment initiation, interruption and
      modification: examination of patients diagnosed with advanced HIV in Australia.
AB  - INTRODUCTION: HIV prevention strategies are moving towards reducing plasma HIV
      RNA viral load in all HIV-positive persons, including those undiagnosed,
      treatment naive, on or off antiretroviral therapy. A proxy population for those
      undiagnosed are patients that present late to care with advanced HIV. The
      objectives of this analysis are to examine factors associated with patients
      presenting with advanced HIV, and establish rates of treatment interruption and
      modification after initiating ART. METHODS: We deterministically linked records
      from the Australian HIV Observational Database to the Australian National HIV
      Registry to obtain information related to HIV diagnosis. Logistic regression was
      used to identify factors associated with advanced HIV diagnosis. We used survival
      methods to evaluate rates of ART initiation by diagnosis CD4 count strata and by
      calendar year of HIV diagnosis. Cox models were used to determine hazard of first
      ART treatment interruption (duration >30 days) and time to first major ART
      modification. RESULTS: Factors associated (p<0.05) with increased odds of
      advanced HIV diagnosis were sex, older age, heterosexual mode of HIV exposure,
      born overseas and rural-regional care setting. Earlier initiation of ART occurred
      at higher rates in later periods (2007-2012) in all diagnosis CD4 count groups.
      We found an 83% (69, 91%) reduction in the hazard of first treatment interruption
      comparing 2007-2012 versus 1996-2001 (p<0.001), and no difference in ART
      modification for patients diagnosed with advanced HIV. CONCLUSIONS: Recent HIV
      diagnoses are initiating therapy earlier in all diagnosis CD4 cell count groups,
      potentially lowering community viral load compared to earlier time periods. We
      found a marked reduction in the hazard of first treatment interruption, and found
      no difference in rates of major modification to ART by HIV presentation status in
      recent periods.

PMID- 25865378
TI  - Obstacles to creating an environment conducive to HIV prevention for young
      people.
AB  - The external environment of an organisation influences the desired goals and
      interventions of that organisation in many ways. However, strategies for
      influencing the external context to create a more enabling environment for the
      interventions of non-governmental organisations (NGOs) are often inadequately
      addressed. This article draws on an empirical multiple-case study conducted in
      2007/08 of four NGOs providing HIV-prevention services to young people in several
      low-resource, high-HIV-prevalence communities in Cape Town, South Africa. In an
      earlier study, young people reported that the external environment hampered their
      ability to institutionalise HIV-prevention messages. The current study explored
      how the NGOs endeavoured to influence the external environment, and the
      challenges they faced. The findings show that the NGOs practised a combination of
      strategies, encompassing inter-organisational relationships, influencing policy,
      and championing by example. Key constraints to their influencing practices
      included fear of losing legitimacy as a service provider; inadequate knowledge,
      skills and opportunity; perceived deviation from their usual work; inadequate
      funding; conflicts over values and messages; and a habit of focusing more on
      young people's individual behaviours and less on context. The development
      management task of influencing the external environment to create an environment
      more conducive to HIV prevention seemed constrained mainly because: 1) donors
      focused on funding and monitoring the activities they were interested in and
      conceptualised as HIV-prevention services; 2) NGO efforts were restricted to
      programme implementation based on agreed deliverables, thus influencing was
      mainly confined to championing by example; consequently, 3) 'influencing efforts'
      to create an environment more conducive to HIV prevention were left mainly to
      young people themselves, who can affect their peers only to a narrow, albeit
      crucial extent. The external environment thus remains adverse to HIV prevention. 

PMID- 25865379
TI  - Health-promoting practices and the factors associated with self-reported poor
      health in caregivers of children orphaned by AIDS in southwest Uganda.
AB  - Informal caregivers worldwide are faced with the dilemma of maintaining their
      health and meeting the caregiving demands of their loved ones. This study
      explores the health outcomes of caregiving, caregivers' health-promoting
      practices and the challenges to providing care among caregivers to children
      orphaned by AIDS in southwest Uganda. A descriptive design and interview
      questionnaires were used to collect data from 204 caregivers. The average age of
      the caregivers was 41.36 (+/-10.9) years and most of them (53%) were grandmothers
      to the orphans. The majority (65%) of the caregivers were caring for at least
      three orphans, had been in the caregiver role for more than five years (61%), and
      stated that their health had been negatively impacted by caregiving (61%).
      According to self-reports, the most common new health problems since taking up
      the caregiving role were chronic ill health (97%), social isolation (95%) and
      mental stress (92%). The health-promoting practices most often engaged in were
      eating a balanced diet (67%), seeking spiritual support (58%), and performing
      self-care activities (44%). The challenges to caregiving most often reported were
      poverty (88%) and a lack of time to seek personal medical care (59%). The
      predictors of self-reported poor health among the caregivers were stress (odds
      ratio [OR] = 3.43; p <= 0.01), caring for three or more orphans (OR = 2.19; p <=
      0.01), female gender (OR = 1.77; p <= 0.01), and having spent more than five
      years as a caregiver to an orphan (OR = 1.35; p <= 0.01). The findings suggest
      that caregivers commonly experience poor health and their health-promoting
      practices are inadequate. There is a need for organised and formal health
      promotion programmes for caregivers of children orphaned by AIDS, especially in
      rural areas of developing countries. Interventions for health promotion can be
      achieved through integrated programmes that provide health education, social
      services, respite from caregiving and counselling. 

PMID- 25865380
TI  - Adolescents' perceptions of sexual coercion in Uganda.
AB  - In Uganda, HIV prevalence remains high with young people at higher risk of
      infection than adults. Much is known about the sexual risk factors for HIV
      transmission among youths, including sexual encounters that are coerced. On the
      other hand, relatively little is known about the barriers to preventing sexual
      coercion and what strategies may overcome those barriers with adolescents. We
      conducted three focus group discussions with adolescents in an urban area in
      Uganda to understand their perceptions of sexual coercion, and to identify, from
      their point of view, how coercion can be addressed. Data were collected to inform
      the development of an Internet-based programme for young people, tailored to
      their HIV-information, motivation and behavioural-skills needs. The findings
      suggest that the participants perceived adults' coercion of young people as
      common. The secondary school participants also expressed confusion over what
      exactly constituted coercion. They acknowledged that young people lack skills to
      avoid coerced sex and felt it would be critical to give youths information on the
      circumstances in which coercion may occur and its links to HIV risk. Finally, the
      youths wanted specific skills and to be empowered to avoid sexual coercion and to
      report rape. The findings suggest that adolescents are open to discussions about
      this topic and they support the call for greater integration of coercion
      reduction strategies in HIV-prevention programmes targeted at their age group. 

PMID- 25865381
TI  - Effect of health education on oral hygiene and gingival status of persons living
      with HIV attending comprehensive care centres in Nairobi, Kenya.
AB  - The study aimed to describe the effect of an oral health education intervention
      on oral hygiene status and gingival inflammation among persons with HIV attending
      two comprehensive healthcare centres in Nairobi, Kenya. This was a quasi
      experimental study of 195 participants (with 102 in the intervention group, and
      93 serving as the control group) who were selected using stratified random
      sampling. The data were collected at baseline, at three months (review 1), and at
      six months (review 2) using an interviewer-administered World Health Organization
      clinical examination form. The prevalence of plaque among the participants in the
      intervention decreased from 70.6% to 18.6%, with a significant decrease in their
      mean plaque score, from 0.89 to 0.15. The prevalence of gingival inflammation in
      the intervention group decreased from 58.2% to 12.7%, with a significant decrease
      in the mean gingival score, from 0.66 to 0.11. No significant change in degree of
      oral hygiene and gingival inflammation was observed among the non-intervention
      group. There was a strong association between the change in the mean gingival
      score and the change in the mean plaque score between baseline and at six months
      for the intervention group. The regression analysis yielded a coefficient of
      determination (r2) of 0.76; therefore, 76% of the variation in change in gingival
      score was explained by the variables in the equation. Only the change in mean
      plaque score was a significant predictor of the change in gingival score. 

PMID- 25865382
TI  - Nationwide outbreak of multidrug-resistant Salmonella Heidelberg infections
      associated with ground turkey: United States, 2011.
AB  - On 23 May 2011, CDC identified a multistate cluster of Salmonella Heidelberg
      infections and two multidrug-resistant (MDR) isolates from ground turkey retail
      samples with indistinguishable pulsed-field gel electrophoresis patterns. We
      defined cases as isolation of outbreak strains in persons with illness onset
      between 27 February 2011 and 10 November 2011. Investigators collected hypothesis
      generating questionnaires and shopper-card information. Food samples from homes
      and retail outlets were collected and cultured. We identified 136 cases of S.
      Heidelberg infection in 34 states. Shopper-card information, leftover ground
      turkey from a patient's home containing the outbreak strain and identical
      antimicrobial resistance profiles of clinical and retail samples pointed to plant
      A as the source. On 3 August, plant A recalled 36 million pounds of ground
      turkey. This outbreak increased consumer interest in MDR Salmonella infections
      acquired through United States-produced poultry and played a vital role in
      strengthening food safety policies related to Salmonella and raw ground poultry. 

PMID- 25865383
TI  - Evaluation of the Performance and Safety of a Newly Developed Intravenous Fluid
      Warmer.
AB  - To evaluate the performance and safety of a newly developed blood warmer
      (ThermoSens), we tested its heating capability under various conditions using
      isotonic saline and hemolysis analysis with swine blood. The following two in
      vitro tests were performed: (i) To investigate the performance of the device, the
      inflow and outflow temperatures were measured at various flow rates (30, 50, and
      100 mL/min) using cold (5 degrees C) and room temperature (20 degrees C) isotonic
      saline (0.9%). Several parameters were measured including the highest temperature
      of the outlet, the time required to reach the highest temperature, and the
      temperature of the intravenous line. (ii) To investigate the safety of the
      device, a hemolysis test was performed using swine blood. We obtained 320 mL of
      whole blood from swine and refrigerated the blood for 35 days at 3 degrees C. In
      order to replicate the clinical situation, blood flow by gravity and pressure
      (300 mm Hg) was used. Before and after the heating test, blood samples were
      obtained and a comparison was made between these samples. Hemoglobin, hematocrit,
      lactate dehydrogenase, and plasma hemoglobin were used for red blood cell (RBC)
      damage analysis. The highest outlet temperatures obtained using flow rates of 30,
      50, and 100 mL/min were 39.10 +/- 0.59, 39.25 +/- 0.69, and 37.63 +/- 1.03
      degrees C, respectively, with cold saline, and 39.40 +/- 0.40, 39.66 +/- 0.36,
      and 39.49 +/- 0.49 degrees C, respectively, with room temperature saline.
      Hemolysis tests showed no significant changes in hemoglobin, hematocrit, lactate
      dehydrogenase, or plasma hemoglobin (P > 0.05) between before and after heating
      for both gravity and pressure blood flow. The ThermoSens blood warmer warms
      isotonic saline effectively, reaching temperatures up to 36 degrees C under
      various conditions. Hemolysis tests showed no RBC damage. Therefore, the newly
      developed ThermoSens has good heating performance and is safe for RBC products. 

PMID- 25865384
TI  - Retrieval of proximally migrated biliary stent with direct peroral cholangioscopy
      with an ultraslim endoscope.

PMID- 25865385
TI  - Ruptured varix: tips to tackle the demon.

PMID- 25865386
TI  - Recanalization of a complete postradiation esophageal obstruction with endoscopic
      submucosal dissection techniques.

PMID- 25865387
TI  - Open-access endoscopy.
AB  - OAE is commonly used. The majority of patients referred for OAE are considered
      appropriate for endoscopy according to ASGE guidelines. Most patients undergoing
      OAE procedures are knowledgeable about the study and are satisfied with the
      experience. Several potential problems have been identified, including
      inappropriate referrals, communication errors, and inadequately prepared or
      informed patients. OAE can be safely used if preprocedure assessment, informed
      consent, information transfer, patient safety, and satisfaction are addressed in
      all cases.

PMID- 25865388
TI  - Fluorescence cytology with 5-aminolevulinic acid in EUS-guided FNA as a method
      for differentiating between malignant and benign lesions (with video).
AB  - BACKGROUND: EUS-guided FNA (EUS-FNA) has been increasingly performed to obtain
      specimens for the pathological evaluation of patients with GI and
      pancreaticobiliary masses as well as lymphadenopathies of unknown origin.
      Photodynamic diagnosis by using 5-aminolebulinic acid (ALA) has been reported to
      be useful for enabling the visual differentiation between malignant and normal
      tissue in various cancers. OBJECTIVE: To evaluate the diagnostic accuracy of
      fluorescence cytology with ALA in EUS-FNA. DESIGN: A prospective study. SETTING:
      A single center. PATIENTS: A total of 28 consecutive patients who underwent EUS
      FNA for the pathological diagnosis of a pancreaticobiliary mass lesion or intra
      abdominal lymphadenopathy of unknown origin. INTERVENTIONS: Patients were orally
      administered ALA 3 to 6 hours before EUS-FNA. The sample was obtained via EUS-FNA
      for fluorescence cytology and conventional cytology. A single gastroenterologist
      performed the fluorescence cytology by using fluorescence microscopy after the
      procedure, independently of the conventional cytology by pathologists. MAIN
      OUTCOME MEASUREMENTS: The accuracy of fluorescence cytology with ALA in the
      differentiation between benign and malignant lesions by comparing the results of
      fluorescence cytology with the final diagnosis. RESULTS: Of the 28 patients
      included in the study, 22 were considered as having malignant lesions and 6
      patients as having benign lesions. Fluorescence cytology could correctly
      discriminate between benign and malignant lesions in all patients. Therefore,
      both the sensitivity and specificity of fluorescence cytology were 100% in our
      study. LIMITATIONS: Fluorescence cytology was performed by only 1
      gastroenterologist with a small number of patients. CONCLUSION: Fluorescence
      cytology with ALA in EUS-FNA may be an effective and simple method for
      differentiating between benign and malignant lesions.

PMID- 25865389
TI  - Flexible endoscopic Zenker's diverticulotomy.

PMID- 25865390
TI  - Contrast enhanced imaging of human meniscus using cone beam CT.
AB  - OBJECTIVE: Meniscal injuries can lead to mechanical overloading of articular
      cartilage and eventually to knee osteoarthritis. The objective was to evaluate
      the potential of contrast enhanced computed tomography (CECT) to image contrast
      agent (CA) diffusion in human menisci with a clinical cone beam CT scanner.
      DESIGN: Isolated human menisci (n = 26) were imaged using magnetic resonance
      imaging (MRI) and CECT in situ. Diffusion of anionic CA into the meniscus was
      imaged for up to 30 h. The results of CECT were compared with water, collagen and
      proteoglycan (PG) contents, biomechanical properties, age and histological and MR
      images of the samples. RESULTS: Diffusion of CA required over 25 h to reach
      equilibrium. The CA partition (the CA concentration in the tissue divided by that
      in the bath) at the 40 min time point correlated significantly with that at the
      30 h time point in both lateral (r = 0.706, P = 0.007) and medial (r = 0.669, P =
      0.012) menisci. Furthermore, CA partition in meniscus after 30 h of diffusion
      agreed qualitatively with the distribution of PGs. CONCLUSION: The cross
      sectional distribution of CA was consistent with that reported in a previous MUCT
      study on bovine meniscus. The time required to reach diffusion equilibrium was
      found impractical for clinical applications. However, based on the present
      results, shorter delay between injection and imaging (e.g., 40 min) could be
      feasible in clinical diagnostics of meniscal pathologies.

PMID- 25865391
TI  - Identifying potential working mechanisms behind the positive effects of exercise
      therapy on pain and function in osteoarthritis; a systematic review.
AB  - OBJECTIVE: Although physical exercise is the commonly recommended for
      osteoarthritis (OA) patients, the working mechanism behind the positive effects
      of physical exercise on pain and function is a black box phenomenon. In the
      present study we aimed to identify possible mediators in the relation between
      physical exercise and improvements of pain and function in OA patients. DESIGN: A
      systematic search for all studies evaluating the effects of physical exercise in
      OA patients and select those that additionally reported the change in any
      physiological factor from pre-to post-exercise. RESULTS: In total, 94 studies
      evaluating 112 intervention groups were included. Most included studies evaluated
      subjects with solely knee OA (96 out of 112 groups). Based on the measured
      physiological factors within the included studies, 12 categories of possible
      mediators were formed. Muscle strength and ROM/flexibility were the most measured
      categories of possible mediators with 61 and 21 intervention groups measuring one
      or more physiological factors within these categories, respectively. 60% (31 out
      of 52) of the studies showed a significant increase in knee extensor muscle
      strength and 71% (22 out of 31) in knee flexor muscle strength over the
      intervention period. All 5 studies evaluating extension impairments and 10 out of
      12 studies (83%) measuring proprioception found a significant change from pre-to
      post-intervention. CONCLUSION: An increase of upper leg strength, a decrease of
      extension impairments and improvement in proprioception were identified as
      possible mediators in the positive association between physical exercise and OA
      symptoms.

PMID- 25865393
TI  - Ucma, a direct transcriptional target of Runx2 and Osterix, promotes osteoblast
      differentiation and nodule formation.
AB  - OBJECTIVE: Runt-related transcription factor 2 (Runx2) and Osterix (Osx) are the
      master transcription factors in bone formation. Nonetheless, genes acting
      downstream of both Runx2 and Osx have yet to be fully characterized. Here, we
      investigate the downstream targets of both Runx2 and Osx in osteoblasts.
      MATERIALS AND METHODS: DNA microarray analysis was conducted on calvarial RNA
      from wild-type, Runx2 heterozygous, Osx heterozygous, and Runx2/Osx double
      heterozygous embryos. Expression and transcriptional responses of the selected
      target gene were analyzed in MC3T3-E1 osteoblastic cells. RESULTS: The expression
      of unique cartilage matrix-associated protein (Ucma) was decreased in Runx2/Osx
      double heterozygous embryos. In contrast, Ucma expression was increased in
      osteoblasts overexpressing both Runx2 and Osx. Ucma expression was initiated mid
      way through osteoblast differentiation and continued throughout the
      differentiation process. Transcriptional activity of the Ucma promoter was
      increased upon transfection of the cells with both Runx2 and Osx. Runx2-and Osx
      mediated activation of the Ucma promoter was directly regulated by Runx2-and/or
      Sp1-binding sites within its promoter. During osteoblast differentiation, the
      formation of mineralized nodules in Ucma-overexpressing stable clones occurred
      earlier and was more enhanced than that in the mock-transfected control.
      Mineralized nodule formation was strongly augmented in the cells cultured in a
      medium containing secretory Ucma proteins. CONCLUSION: Ucma is a novel downstream
      gene regulated by both Runx2 and Osx and it stimulates osteoblast differentiation
      and nodule formation.

PMID- 25865392
TI  - Call for standardized definitions of osteoarthritis and risk stratification for
      clinical trials and clinical use.
AB  - Osteoarthritis (OA) is a heterogeneous disorder. The goals of this review are (1)
      To stimulate use of standardized nomenclature for OA that could serve as building
      blocks for describing OA and defining OA phenotypes, in short to provide unifying
      disease concepts for a heterogeneous disorder; and (2) To stimulate establishment
      of ROAD (Risk of OA Development) and ROAP (Risk of OA Progression) tools
      analogous to the FRAXTM instrument for predicting risk of fracture in
      osteoporosis; and (3) To stimulate formulation of tools for identifying disease
      in its early preradiographic and/or molecular stages - REDI (Reliable Early
      Disease Identification). Consensus around more sensitive and specific diagnostic
      criteria for OA could spur development of disease modifying therapies for this
      entity that has proved so recalcitrant to date. We fully acknowledge that as we
      move forward, we expect to develop more sophisticated definitions, terminology
      and tools.

PMID- 25865394
TI  - It's not all about the knee adduction moment: the role of the knee flexion moment
      in medial knee joint loading.

PMID- 25865395
TI  - Molecular tools and bumble bees: revealing hidden details of ecology and
      evolution in a model system.
AB  - Bumble bees are a longstanding model system for studies on behaviour, ecology and
      evolution, due to their well-studied social lifestyle, invaluable role as wild
      and managed pollinators, and ubiquity and diversity across temperate ecosystems.
      Yet despite their importance, many aspects of bumble bee biology have remained
      enigmatic until the rise of the genetic and, more recently, genomic eras. Here,
      we review and synthesize new insights into the ecology, evolution and behaviour
      of bumble bees that have been gained using modern genetic and genomic techniques.
      Special emphasis is placed on four areas of bumble bee biology: the evolution of
      eusociality in this group, population-level processes, large-scale evolutionary
      relationships and patterns, and immunity and resistance to pesticides. We close
      with a prospective on the future of bumble bee genomics research, as this rapidly
      advancing field has the potential to further revolutionize our understanding of
      bumble bees, particularly in regard to adaptation and resilience. Worldwide, many
      bumble bee populations are in decline. As such, throughout the review,
      connections are drawn between new molecular insights into bumble bees and our
      understanding of the causal factors involved in their decline. Ongoing and
      potential applications to bumble bee management and conservation are also
      included to demonstrate how genetics- and genomics-enabled research aids in the
      preservation of this threatened group. 

PMID- 25865396
TI  - Diabetic cardiomyopathy: Role of epidermal growth factor receptor tyrosine
      kinase.

PMID- 25865397
TI  - Development and Psychometric Testing Chinese Version of the Frommelt Attitude
      Toward Care of the Dying Scale, Form B in Nurses and Nursing Students.
AB  - Nursing students' and nurses' attitudes toward caring for the dying need to be
      explored. The Frommelt Attitude Toward Care of the Dying (FATCOD) scale has not
      previously been used in the Chinese language. The aim of this study was to
      examine the reliability and validity of the Chinese version of the FATCOD scale.
      A convenience sample of 154 nurses and 200 nursing students was recruited. The
      Chinese version of the FATCOD was used to test construct validity, concurrent
      validity, convergent validity, and internal consistency. The Cronbach's alpha
      coefficient of the Chinese version of the FATCOD scale, Form B (FATCOD-B-C) was
      0.790. The Cronbach's alpha coefficients for each subscale ranged from 0.610 to
      0.863. The test-retest reliability was satisfactory (r = 0.959, P < 0.001). The
      overall content validity index was 0.92. Seven factors were identified in
      exploratory factor analysis. The results provide preliminary support for the
      reliability and validity of the FATCOD-B-C in nurses and nursing students.
      Additional psychometric testing is recommended to confirm the factor analysis,
      but this study provides further evidence of the applicability of the FATCOD-B-C
      in clinical care services.

PMID- 25865398
TI  - Print Material in Cancer Prevention: an Evaluation of Three Booklets Designed
      with and for Alaska's Community Health Workers.
AB  - With increased internet access in rural Alaska and subsequent shifts in access to
      health information, we sought to understand the current role of printed cancer
      education booklets focused on recommended cancer screening exams. This evaluation
      reviewed three cancer education booklets specifically created with and for
      Alaska's Community Health Workers (CHWs) and the people in their communities. The
      booklets were created in an adaptation of empowerment theory, focused on working
      within a community-based participatory framework, in a culturally respectful
      manner, to shift cancer prevention norms by empowering CHWs to catalyze health
      behavior change for both themselves and their communities. The booklets
      incorporated traditional Alaska Native values and were designed to connect with
      readers at an affective and informational place that emphasized relationships.
      Since 2010, over 20,000 booklets have been distributed. Between January 2013 and
      March 2014, CHWs from throughout Alaska were invited to complete a three-page
      anonymous written evaluation of the booklets during community health trainings in
      Anchorage, Alaska. A total of 102 CHWs completed evaluations, with the vast
      majority indicating that they liked (100 %), and learned (96 %) from, the
      booklets. The evaluation results suggest that printed booklets designed in a
      culturally responsive manner, which both communicate medically accurate
      information and reach readers at an affective place to inspire action through
      raising awareness in relationship with others, are a helpful way to receive,
      discuss, and disseminate cancer screening information among Alaska Native people.

PMID- 25865399
TI  - "Obesity is the New Major Cause of Cancer": Connections Between Obesity and
      Cancer on Facebook and Twitter.
AB  - Social media interactions can inform public health risk perceptions. While
      research has examined the risk relationships between obesity and cancer, public
      attitudes about their associations remain largely unknown. We explored how these
      constructs were discussed together on two social media platforms. Publicly
      accessible Facebook and Twitter posts from a 2-month period in 2012 containing
      references to obesity ("obese/obesity," "overweight," and "fat") and cancer
      related words were extracted (N = 3702 posts). Data cleaning yielded a final set
      of 1382 posts (Facebook: N = 291; Twitter: N = 1091). Using a mixed-methods
      approach, themes were inductively generated, and sentiment valence, structural
      elements, and epistemic stance were coded. Seven relational themes emerged:
      obesity is associated with cancer (n = 389), additional factors are associated
      with both obesity and cancer (n = 335), obesity causes cancer (n = 85), cancer
      causes obesity (n = 6), obesity is not linked to cancer (n = 13), co-occurrence
      (n = 492), and obesity is valued differently than cancer (n = 60). Fifty-nine
      percent of posts focused on an associative or causal link between obesity and
      cancer. Thirty-one percent of posts contained positive and/or negative sentiment.
      Facebook was more likely to contain any sentiment, but Twitter contained
      proportionately more negative sentiment. Concurrent qualitative analysis revealed
      a dominance of individual blame for overweight/obese persons and more support and
      empathy for cancer survivors. Our study reflects wide recognition of the evidence
      linking obesity to increased risk of cancer, a diverse set of factors perceived
      to be dually associated with both conditions and differing attribution of
      responsibility. We demonstrate that social media monitoring can provide an
      important gauge of public health risk perception.

PMID- 25865400
TI  - Engaging Elements of Cancer-Related Digital Stories in Alaska.
AB  - The tradition of storytelling is an integral part of Alaska Native cultures that
      continues to be a way of passing on knowledge. Using a story-based approach to
      share cancer education is grounded in Alaska Native traditions and people's
      experiences and has the potential to positively impact cancer knowledge,
      understandings, and wellness choices. Community health workers (CHWs) in Alaska
      created a personal digital story as part of a 5-day, in-person cancer education
      course. To identify engaging elements of digital stories among Alaska Native
      people, one focus group was held in each of three different Alaska communities
      with a total of 29 adult participants. After viewing CHWs' digital stories
      created during CHW cancer education courses, focus group participants commented
      verbally and in writing about cultural relevance, engaging elements, information
      learned, and intent to change health behavior. Digital stories were described by
      Alaska focus group participants as being culturally respectful, informational,
      inspiring, and motivational. Viewers shared that they liked digital stories
      because they were short (only 2-3 min); nondirective and not preachy; emotional,
      told as a personal story and not just facts and figures; and relevant, using
      photos that showed Alaskan places and people.

PMID- 25865401
TI  - [Trends in cohort effects of cardiovascular disease mortality in Japan, 1950
      2010].
AB  - OBJECTIVES: The average systolic blood pressure value among Japanese individuals
      has decreased rapidly from a peak in 1965 to 1990, and cardiovascular disease
      mortality has correspondingly decreased. The age-adjusted ischemic heart disease
      mortality rate has also decreased. However, the westernized lifestyle, with its
      associated effects on development of cardiovascular disease, is increasing
      rapidly in Japan. Consequently, there are concerns that the current reduction in
      the cardiovascular disease mortality rate will cease and actually increase in the
      near future. We used an age-period-cohort (APC) model to decompose cardiovascular
      disease mortality trends into individual effects of age, period, and cohort to
      analyze the cohort effects of cardiovascular disease. METHODS: We used 5-year
      interval vital statistical data from 1950-2010 to create 13 classes. Subjects
      aged 30-89 years were divided into 5-year age groups to create 12 classes. Birth
      cohorts in this analysis included individuals born from 1861 to 1865, which
      corresponded to individuals aged, 85 to 89 years in 1950, up to individuals born
      from 1976 to 1980, who were 30 to 34 years old in 2010. A total of 24 groups were
      created. We estimated the effect of each characteristic using the sequential
      method in APC analysis with the assumption that age effects are predominant.
      RESULTS: The period effects of cardiovascular disease mortality declined
      consistently. However, the cohort effects, which declined until the cohort born
      in 1988, stopped declining or increased slightly in men and women born around
      1938 and 1943, respectively. CONCLUSION: The results showed a consistent decline
      in period effects on cardiovascular mortality, which presumably reflect improved
      living, healthcare, and medical environments. However, analysis of cohort effects
      did not show a steady decline in younger generations. Decreased average systolic
      blood pressure among Japanese citizens is associated with reduced risk of
      cardiovascular disease. If a westernized lifestyle also plays a part in the
      cohort effects and is associated with the observed slowdown or cessation of
      reduced systolic blood pressure, it is possible that the number of cardiovascular
      deaths may increase in younger generations. This possibility needs to be taken
      into consideration in future implementation of public health activities.

PMID- 25865402
TI  - [Health effects of interventions to promote physical activity in survivors of the
      2011 Great East Japan Earthquake. A longitudinal study].
AB  - OBJECTIVES: Interventions that promote physical activity to prevent psychological
      distress and disuse syndromes were carried out in disaster-stricken areas.
      However, the effect of these interventions to promote physical activity in
      disaster-stricken areas has not yet been fully clarified. The purpose of this
      study was to examine the health effects of promoting physical activity in a
      disaster-stricken area. METHODS: We conducted an exercise intervention as part of
      a health survey project among residents of Ishinomaki-city, Miyagi, Japan in
      2012. To determine if changes in health condition differed between intervention
      participants and nonparticipants, health condition data from 81 participants were
      compared with data from 81 nonparticipants selected by propensity score matching.
      Factors including sex, age, original address (pre-quake), and six outcome
      variables (psychological distress [K6 score], subjective health status, sleep
      duration, sleep quality, frequency of outings, and time spent walking) were used
      for matching. A linear mixed model was used for statistical analysis. RESULTS:
      There were no significant differences in K6 score between participants and
      nonparticipants (P=0.913). Significant improvements were observed in subjective
      health status (P=0.011) and outing frequency (P=0.002), but not in other outcome
      variables. CONCLUSION: Subjective health status and outing frequency were
      significantly improved among participants of the exercise intervention. Exercise
      intervention may be an effective public health strategy in disaster-stricken
      areas.

PMID- 25865403
TI  - [Actual circumstances of suicides and related factors according to newspaper
      coverage of television programs].
AB  - OBJECTIVES: This study investigated the actual circumstances of suicides and
      related factors based on TV program pages in newspapers. METHODS: Information was
      extracted from the television schedule columns of one major newspaper introducing
      programs from 2004 to June 2009. During information extraction, reliability was
      maintained by having 2 researchers specializing in mental health make
      determinations independently. We examined the column for program names and
      introductions of 6 broadcast TV channels within the television schedule for data
      analysis. After information was extracted using the established selection
      criteria regarding suicide and related information, information extraction was
      performed for sub-themes in the TV programs. Information was also classified with
      regard to specialization and program genre or other related context as well as
      the presence or absence of an experiential narrative. In addition to carrying out
      the qualitative classification of these collected information data, we compared
      the numbers and proportion (%) in chronological order and context. Moreover,
      programs dealing repeatedly with one case were analyzed for trends in the
      contents of program introductions and in the media. RESULTS: Depending on the
      season, some programs constantly broadcast about suicides, mainly in spring and
      autumn. Most of these programs air on Tuesday and Wednesday. We also analyzed
      programs that repeatedly discussed the same case and identified eight cases
      repeatedly discussed by more than ten different programs. We also considered
      bullying, homicide, and depression, which appeared most frequently as subthemes
      of suicide. An unprofessional approach was observed in 504 programs (81%),
      whereas only 47 (7.6%) showed expertise. CONCLUSION: Depending on the season and
      day of the week, suicide is constantly broadcasted on TV programs. We also
      considered mental health because bullying was a common subtheme in this context.
      An unprofessional approach was seen in most programs. We also studied programs
      that repeatedly discussed the same case because overexposure of offenders in
      programs can lead to secondary suicides.

PMID- 25865405
TI  - Gingival crevicular blood for screening of blood glucose level in patients with &
      without diabetes: a chair-side test.
AB  - OBJECTIVES: Diabetes is a pandemic disease with increasing prevalence and serious
      complications. Periodontitis being one of its presentation and is its sixth
      recognized complication. This study compares blood glucose levels in gingival
      crevicular blood of patients with and without diabetes elicited during routine
      periodontal probing and venous blood sample. METHODS: Seventy patients with
      moderate gingivitis and periodontitis positive for bleeding on probing were
      chosen. All the subjects were divided in two groups, group I consisted of 35
      diabetic and group II of 35 non-diabetic subjects. Blood from the gingiva of the
      most inflamed site was collected with the test strip of a glucose self-monitoring
      device, and the blood glucose levels were measured. At the same time, intravenous
      blood was collected for measurement in a laboratory glucose analyzer. Gingival
      index and probing pocket depth were evaluated for each subject at same time.
      RESULTS: The mean GCB levels and VB derived from all samples were 156.07 +/-
      49.23 mg dl(-1) and 156 +/- 49.89 mg dl(-1) , respectively, for diabetic group
      and 90.80 +/- 11.07 and 93.41 +/- 9.30 for non-diabetic group. In both the
      groups, the difference between GCB and VB glucose levels was non-significant (P >
      0.005). Highly significant correlation between GCB and VB (r = 0.972 for diabetic
      and r = 0.721 for non-diabetic) in both the groups was found. CONCLUSION: The
      data from this study show that GCB collected during diagnostic periodontal
      examination can be an excellent source for estimation of blood sugar or
      glucometric analysis. This technique is also suitable for routine screening of
      diabetic and early diagnosis of unknown diabetic cases.

PMID- 25865406
TI  - Molecular analysis of the F167Y SNP in the beta-tubulin gene by screening
      genotypes of two Ancylostoma caninum populations.
AB  - Mutations in the beta-tubulin isotype 1 gene at codons 167 (F167Y), 198 (E198A)
      and 200 (F200Y) have been associated with benzimidazole resistance in helminths.
      The F200Y polymorphism has previously been described for Ancylostom caninum;
      however, the F167Y polymorphism has not been investigated in members of the
      Ancylostomatidae family. The aim of this study was to screen for the F167Y
      polymorphism in A. caninum isolates recovered from naturally infected dogs in two
      Brazilian states. No mutation was observed at codon 167 in the 230 analyzed
      samples from the two populations; however, it is possible that this change may be
      present at a low frequency in other populations of the same species. These
      results highlight the importance of monitoring the genetic basis involved in the
      drug resistance process. 

PMID- 25865407
TI  - Optimization of gold nanoparticle photoluminescence by alkanethiolation.
AB  - Surface thiolation affects the size of gold nanoparticles and the presence of
      visible luminescence under UV stimulation. We explored these phenomena by
      analysing alkanethiolate coatings with different carbon chain lengths, from 3
      mercaptopropionic acid to 16-mercaptohexadecanoic acid, synthesized by intense X
      ray irradiation. Photoluminescence is present for the smallest nanoparticles, but
      its intensity becomes more intense as the carbon chain length increases,
      achieving a quantum efficiency of 28% with a 16-mercaptohexadecanoic acid
      coating. 

PMID- 25865408
TI  - Scleral lens influence on corneal curvature and pachymetry in keratoconus
      patients.
AB  - OBJECTIVES: To investigate the influence of full scleral lenses on corneal
      curvature and pachymetry in keratoconus patients. METHODS: In this intervention
      study, 20 eyes of 14 patients were measured by Scheimpflug imaging (Pentacam HR,
      Oculus) at two time points: directly and >=1 week after scleral lens removal.
      Steep, flat and maximal keratometry (K(steep), K(flat) and K(max)) and optical
      pachymetry were analyzed. A generalized estimating equation analysis was
      performed to correct for paired eyes. RESULTS: Directly after scleral lens
      removal, all three curvature parameters were significantly flatter compared to
      >=1 week after scleral lens removal. Average K(steep) was 0.7 diopter (D) lower
      (P<0.001), average K(flat) was 0.5D lower (P=0.037) and average K(max) was 1.1D
      lower (P<0.001). Directly after scleral lens removal, average optical pachymetry
      was +/-2.5% higher (P<0.001) compared to >=1 week after scleral lens removal.
      CONCLUSIONS: Although scleral lenses do not mechanically touch the cornea,
      curvature and pachymetry seem to be influenced by scleral lens wear in
      keratoconus patients. The duration of these changes remain unclear.

PMID- 25865409
TI  - Opportunities of marker-assisted selection for rice fragrance through marker
      trait association analysis of microsatellites and gene-based markers.
AB  - Developing fragrant rice through marker-assisted/aided selection (MAS) is an
      economical and profitable approach worldwide for the enrichment of an elite
      genetic background with a pleasant aroma. The PCR-based DNA markers that
      distinguish the alleles of major fragrance genes in rice have been synthesised to
      develop rice scent biofortification through MAS. Thus, the present study examined
      the aroma biofortification potential of these co-dominant markers in a germplasm
      panel of 189 F2 progeny developed from crosses between a non-aromatic variety
      (MR84) and a highly aromatic but low-yielding variety (MRQ74) to determine the
      most influential diagnostic markers for fragrance biofortification. The SSRs and
      functional DNA markers RM5633 (on chromosome 4), RM515, RM223, L06, NKSbad2,
      FMbadh2-E7, BADEX7-5, Aro7 and SCU015RM (on chromosome 8) were highly associated
      with the 2AP (2-acetyl-1-pyrroline) content across the population. The alleles
      traced via these markers were also in high linkage disequilibrium (R(2) > 0.70)
      and explained approximately 12.1, 27.05, 27.05, 27.05, 25.42, 25.42, 20.53, 20.43
      and 20.18% of the total phenotypic variation observed for these biomarkers,
      respectively. F2 plants harbouring the favourable alleles of these effective
      markers produced higher levels of fragrance. Hence, these rice plants can be used
      as donor parents to increase the development of fragrance-biofortified tropical
      rice varieties adapted to growing conditions and consumer preferences, thus
      contributing to the global rice market.

PMID- 25865410
TI  - Downregulation of toll-like receptor-mediated signalling pathways in oral lichen
      planus.
AB  - OBJECTIVE: The objective of this study was to investigate the expression of Toll
      like receptors (TLR) and TLR-associated signalling pathway genes in oral lichen
      planus (OLP). METHODS: Initially, immunohistochemistry was used to determine TLR
      expression in 12 formalin-fixed archival OLP tissues with 12 non-specifically
      inflamed oral tissues as controls. RNA was isolated from further fresh samples of
      OLP and non-specifically inflamed oral tissue controls (n = 6 for both groups)
      and used in qRT(2)-PCR focused arrays to determine the expression of TLRs and
      associated signalling pathway genes. Genes with a statistical significance of +/
      two-fold regulation (FR) and a P-value < 0.05 were considered as significantly
      regulated. RESULTS: Significantly more TLR4(+) cells were present in the
      inflammatory infiltrate in OLP compared with the control tissues (P < 0.05).
      There was no statistically significant difference in the numbers of TLR2(+) and
      TLR8(+) cells between the groups. TLR3 was significantly downregulated in OLP (P
      < 0.01). TLR8 was upregulated in OLP, but the difference between the groups was
      not statistically significant. The TLR-mediated signalling-associated protein
      genes MyD88 and TIRAP were significantly downregulated (P < 0.01 and P < 0.05),
      as were IRAK1 (P < 0.05), MAPK8 (P < 0.01), MAP3K1 (P < 0.05), MAP4K4 (P < 0.05),
      REL (P < 0.01) and RELA (P < 0.01). Stress proteins HMGB1 and the heat shock
      protein D1 were significantly downregulated in OLP (P < 0.01). CONCLUSION: These
      findings suggest a downregulation of TLR-mediated signalling pathways in OLP
      lesions.

PMID- 25865411
TI  - The heterogeneous nuclear ribonucleoprotein K (hnRNP K) is a host factor required
      for dengue virus and Junin virus multiplication.
AB  - Heterogeneous nuclear ribonucleoproteins (hnRNPs) are cellular factors involved
      in the replication of several viruses. In this study we analyzed the expression
      and intracellular localization of hnRNP A2 and hnRNP K in cell cultures infected
      with two viruses that cause human hemorrhagic fevers: dengue virus type 2 (DENV
      2) and Junin virus (JUNV). We determined that DENV-2 promoted the cytoplasmic
      translocation of hnRNP K and to a lesser extent of hnRNP A2, meanwhile, JUNV
      infection induced an increase in hnRNP K cytoplasmic localization whereas hnRNP
      A2 remained mainly in the nucleus of infected cells. Both hnRNP K and hnRNP A2
      were localized predominantly in the nucleus of JUNV persistently-infected cells
      even after superinfection with JUNV indicating that persistent infection does not
      alter nucleo-cytoplasmic transport of these hnRNPs. Total levels of hnRNP K
      expression were unaffected by DENV-2 or JUNV infection. In addition we
      determined, using small interfering RNAs, that hnRNP K knockout inhibits DENV-2
      and JUNV multiplication. Our results indicate that DENV-2 and JUNV induce hnRNP K
      cytoplasmic translocation to favor viral multiplication. 

PMID- 25865412
TI  - An exploratory typology of provider responses that encourage and discourage
      conversation about complementary and integrative medicine during routine oncology
      visits.
AB  - OBJECTIVE: To characterize how providers respond to patient mentions of
      complementary and integrative medicine (CIM) during routine oncology visits.
      METHODS: Ethnographic methods were used over a two and a half year period with 82
      advanced cancer patients and their providers across four oncology clinics.
      Participant observation fieldnotes were analyzed using Discourse Analysis.
      RESULTS: CIM was mentioned in 78/229 (34%) of the total observed visits. Patients
      initiated talk about CIM (76%) more than providers (24%). Patients mentioning CIM
      may indicate a preference for or interest in non-pharmacological adjunctive
      treatment options. Providers' responses inhibited further talk in 44% of
      observations and promoted talk in 56% of observations. CONCLUSION: How providers
      respond may indicate their willingness to discuss a range of treatment options
      and to collaboratively engage in treatment decision-making. Provider responses
      that inhibited CIM conversation passed on the opportunity to discuss patient
      preferences, and responses that promoted further conversation helped counsel
      patients about appropriate CIM use. Promoting discussion did not require
      additional time or extensive knowledge about CIM. PRACTICE IMPLICATIONS:
      Providers can facilitate high quality communication without endorsing CIM to help
      patients make treatment decisions and to evaluate CIM appropriateness in response
      to patient values and preferences.

PMID- 25865414
TI  - Daily lives of pre-adolescents/adolescents and their parents after liver
      transplant.
AB  - AIM: This mixed methods study describes the post-transplantation daily life of
      pre-adolescents and adolescents who had undergone living donor liver
      transplantation and their parents. METHODS: Nine parent-child dyads were enrolled
      and all children were living donor liver transplant recipients. Three
      participants were pre-adolescents and the six were adolescents. Five of the
      parents surveyed in this study had been the donors. Members of the parent-child
      dyads completed the questionnaires and participated in semistructured interviews.
      An inductive qualitative analysis of the interview data was conducted. RESULTS:
      The post-transplantation daily life of the parent-child dyads had four distinct
      patterns: (i) pre-adolescents who had undergone transplantation during infancy,
      who had no understanding of the transplant procedure, and whose care was managed
      by their parent(s) without any problems; (ii) adolescents who were aware that
      their physical condition had improved after the transplant and who managed and
      dealt with the situation on their own; (iii) adolescents who were dissatisfied
      with the transplantation and associated immunosuppression because transplant
      procedures were perceived as negative or because they could not remember the
      transplant procedure; and (iv) one participant could not be categorized because
      their liver function deteriorated post-transplantation and they were registered
      for re-transplantation. Patterns were identified that characterized the post
      transplantation daily life of pre-adolescents/adolescents who underwent liver
      transplantation, and that of their parents. Further research for post
      transplantation parent-child dyads is warranted.

PMID- 25865413
TI  - A cross-sectional study of provider and patient characteristics associated with
      outpatient disclosures of dietary supplement use.
AB  - OBJECTIVE: Explore patterns in patients' disclosures of supplement use and
      identify provider and patient characteristics associated with disclosures.
      METHODS: Cross-sectional study of 61 outpatient primary care, integrative
      medicine, and complementary medicine providers, and 603 of their patients.
      Primary outcomes were supplement disclosures (based on audio recorded office
      visits, post-visit patient surveys and medical record abstractions for the day of
      the visits). RESULTS: Seventy-nine percent of 603 patients reported on a post
      visit survey that they took a total of 2107 dietary supplements. Of those taking
      supplements, 232 patients (48.6%) discussed at least one supplement with their
      provider on the day of their office visit. However, patients disclosed only 714
      (33.9%) of the 2107 supplements they were taking. Patients more frequently
      disclosed supplement use when they saw providers who attributed greater
      importance to asking about supplements. Patient characteristics such as patient
      activation, number of medical conditions, and use of prescription medications
      were not associated with disclosure of supplement use. CONCLUSIONS: Provider
      rating of the importance of asking about supplements is a major factor prompting
      patients' disclosures of supplement use. PRACTICE IMPLICATIONS: Provider-targeted
      interventions to encourage provider awareness about potential supplement-drug
      interactions are needed to increase disclosures about dietary supplement use.

PMID- 25865415
TI  - Analgesia and unwanted benzodiazepine effects in point-mutated mice expressing
      only one benzodiazepine-sensitive GABAA receptor subtype.
AB  - Agonists at the benzodiazepine-binding site of GABAA receptors (BDZs) enhance
      synaptic inhibition through four subtypes (alpha1, alpha2, alpha3 and alpha5) of
      GABAA receptors (GABAAR). When applied to the spinal cord, they alleviate
      pathological pain; however, insufficient efficacy after systemic administration
      and undesired effects preclude their use in routine pain therapy. Previous work
      suggested that subtype-selective drugs might allow separating desired
      antihyperalgesia from unwanted effects, but the lack of selective agents has
      hitherto prevented systematic analyses. Here we use four lines of triple GABAAR
      point-mutated mice, which express only one benzodiazepine-sensitive GABAAR
      subtype at a time, to show that targeting only alpha2GABAARs achieves strong
      antihyperalgesia and reduced side effects (that is, no sedation, motor impairment
      and tolerance development). Additional pharmacokinetic and pharmacodynamic
      analyses in these mice explain why clinically relevant antihyperalgesia cannot be
      achieved with nonselective BDZs. These findings should foster the development of
      innovative subtype-selective BDZs for novel indications such as chronic pain. 

PMID- 25865416
TI  - Cytochrome c reacts with cholesterol hydroperoxides to produce lipid- and protein
      derived radicals.
AB  - Lipid peroxidation is a well-known process that has been implicated in many
      diseases. Recent evidence has shown that mitochondrial cholesterol levels are
      increased under specific conditions, making it an important target for
      peroxidation inside the mitochondria. Cholesterol peroxidation generates, as
      primary products, several hydroperoxides (ChOOH), which can react with transition
      metals and metalloproteins. In this sense, cytochrome c (CYTC), a heme protein
      largely found in the mitochondria, becomes a candidate to react with ChOOH. Using
      CYTC associated with SDS micelles to mimic mitochondrial conditions, we show that
      ChOOH induces dose-dependent CYTC Soret band bleaching, indicating that it is
      using ChOOH as a substrate. This reaction leads to protein oligomerization,
      suggesting the formation of a protein radical that, subsequently, recombines,
      giving dimers, trimers, and tetramers. EPR experiments confirmed the production
      of carbon-centered radicals from both protein and lipid in the presence of ChOOH.
      Similar results were obtained with linoleic acid hydroperoxides (LAOOH). In
      addition, replacing SDS micelles by cardiolipin-containing liposomes as the
      mitochondrial mimetic led to similar results with either ChOOH or LAOOH.
      Importantly, kinetic experiments show that CYTC bleaching is faster with ChOOH
      than with H2O2, suggesting that these hydroperoxides could be relevant substrates
      for CYTC peroxidase-like activity in biological media. Altogether, these results
      show that CYTC induces homolytic cleavage of lipid-derived hydroperoxides,
      producing lipid and protein radicals.

PMID- 25865417
TI  - Influence of UVB exposure on the vitamin D status and calcium homoeostasis of
      growing sheep and goats.
AB  - The purpose of this study was to investigate the influence of exposure to
      ultraviolet radiation (UVB) on vitamin D status, intestinal calcium absorption
      and bone metabolism in growing sheep and goats. The hypothesis was that growing
      sheep and goats are able to synthesise vitamin D within their skin as a result of
      UVB exposure and that respective consequences for their vitamin D blood levels
      and the associated parameters can be shown. Fourteen 18-week-old lambs and goat
      kids were kept in an UVB-free environment and randomly assigned to two groups.
      One group was daily exposed to UVB (300 watt) for 12 weeks, and the other served
      as a control group. Except for the exposure to UVB, all animals were kept under
      the same conditions and fed according to their requirements. Before the start of
      the experiment and every second week, blood samples were taken. Also the left
      metatarsus of each animal was analysed by quantitative computer tomography to
      test for bone mineral status before the start, in week 7 and at the end of the
      experiment. After 12 weeks, the animals were slaughtered and samples were taken
      from skin, gastrointestinal tract and kidney for further analyses. In this study,
      exposure to UVB led to increased serum 1,25-dihydroxyvitamin D (1,25VitD) levels
      in goat kids, whereas in lambs, serum 25-hydroxyvitamin D (25VitD) levels were
      increased. In both species UVB-exposed animals showed lower 7-dehydrocholesterol
      (7DHC) values in skin than their respective control groups. These results
      indicate that growing goat kids and lambs are able to synthesise vitamin D in the
      skin when being exposed to UVB.

PMID- 25865418
TI  - Effect of high dietary zinc oxide on the caecal and faecal short-chain fatty
      acids and tissue zinc and copper concentration in pigs is reversible after
      withdrawal of the high zinc oxide from the diet.
AB  - Zinc oxide (ZnO) used in high ('pharmacological') levels to prevent diarrhoea in
      pigs is assumed to reduce copper (Cu) in tissues and inhibits large intestinal
      microbial fermentation. To test it, German Landrace pigs were weaned on d28 of
      age and fed diets containing either 100 (LowZinc, LZn, n = 10) or 3100 mg ZnO/kg
      (HighZinc, HZn, n = 10). The mixed feed (13.0 MJ ME, 18.5% crude protein) was
      based on wheat, barley, soya bean meal and maize. After 4 weeks, the HZn group
      was further fed 100 mg ZnO/kg for another 2 weeks. Caecal contents, faeces and
      tissues were collected after 4 weeks (n = 5 and n = 10 respectively) and 6 weeks
      (n = 5 and n = 5 respectively). Faeces and caecal content were analysed for dry
      matter (DM), pH, ammonia, lactic acid (LA) and short-chain fatty acids (SCFA) on
      native water basis. anova was performed to elucidate significant differences at p
      < 0.05. No diarrhoea occurred. After 4 weeks, the caecal contents' pH increased
      (p < 0.001) and butyric (p < 0.05) and valeric acid (p < 0.01) decreased in the
      HZn group in comparison with LZn. In faeces, a decrease of acetic (p = 0.009),
      butyric (p = 0.007) and valeric acid (p = 0.046), as well as reduced
      acetic:propionic acid (A:P) ratio (p = 0.025) was observed in the HZn group in
      comparison with LZn. Faecal ammonia decreased in HZn (p = 0.018). No differences
      (p > 0.05) were recorded in caecal contents after 6 weeks. In faeces, acetic acid
      remained lower in the HZn group in comparison with LZn (p = 0.006), as did the
      A:P ratio (p = 0.004). Zn concentration in liver, kidneys and ribs, and Cu
      concentrations in kidneys increased in HZn. Withdrawal of ZnO resulted in
      reversibility of the changes. The effect on butyric acid should be discussed
      critically regarding the energetic support for the enterocytes. High Zn and Cu
      tissue concentrations should be considered by pet food producers.

PMID- 25865419
TI  - Preliminary study: fibre content in pet rabbit diets, crude fibre versus total
      dietary fibre.
AB  - Fibre is an important nutrient for rabbit health, and, on commercial pet rabbit
      packaging, it is labelled as crude fibre (CF). In several species, it is
      considered that CF is not an accurate representation of the fibre content in
      feedstuffs. The objective of this study was to compare the CF stated on the label
      (CFL) with laboratory analysis of CF (CFA) and the analysed content of total
      dietary fibre (TDF) in different commercial pet rabbit feeds. We selected 15
      commercial diets and analysed CF and TDF. A mixed model was used to evaluate
      differences between CFL, CFA and TDF, and linear regression was performed to
      study the correlation between CFL and CFA with TDF. CFA and CFL were not
      significantly different (p = 0.836) in the feeds studied, and both were lower
      than TDF (p < 0.001). The correlations between TDF and both CFA and CFL were
      significant (p < 0.001 and p = 0.02, respectively), but the correlation was
      better with CFA (R = 0.86) than with CFL (R = 0.53). As expected, TDF content was
      higher than CF content, an average of two times. These results suggest that the
      CF content in rabbit diets reported on the label is not an appropriate indicator
      of their total fibre content, although further work with a larger sample size is
      required to confirm these results.

PMID- 25865420
TI  - Feed supplemented with organic acids does not affect starch digestibility, nor
      intestinal absorptive or secretory function in broiler chickens.
AB  - The current study aimed to determine the impact of acidified feed on apparent
      ileal starch digestibility, intestinal transport and barrier function and
      intestinal glucose transporter expression. The experiment included a control
      group and a treatment group with broilers fed a standard diet without or with
      1.5% of a commercial organic acid product (64% formic acid, 25% propionic acid,
      11% water). Broilers were fed with the experimental diets from hatching until
      days 32-35. Starch digestibility was determined using 0.2% titanium dioxide as
      ingestible marker. Gene expressions of the intestinal sodium glucose transporter
      1 (SGLT-1) and glucose transporter 2 (GLUT-2) were analysed using qPCR analysis.
      Additionally, SGLT-1 function and chloride secretion were analysed in Ussing
      chamber experiments. Jejunal samples were sequentially exposed to 10 mm glucose,
      100 MUm phloridzin, 100 MUm histamine and 100 MUm carbachol. Apparent ileal
      starch digestibility (+/-SEM) of the control group (97.5 +/- 0.35%) and the acid
      treated group (97.0 +/- 0.59%) did not differ (p = 0.674). The mean tissue
      conductance of intestinal samples obtained from the control group and the
      treatment group was similar [10.6 mS/cm(2) (+/-0.68) and 9.4 mS/cm(2) (+/-0.80)
      respectively (p = 0.147)]. The mean short-circuit currents (DeltaIsc ) of the
      samples exposed to glucose, phloridzin, histamine and carbachol did not differ (p
      > 0.05). Additionally, no differences in the expression of SGLT-1 and GLUT-2
      could be observed (p = 0.942, p = 0.413). Based on this study, the consumption of
      feed supplemented with organic acids was not associated with effects on ileal
      starch digestibility and functional traits of jejunal tissues, indicating that
      these additives have no major impact on the small intestinal function in
      broilers.

PMID- 25865421
TI  - Effects of maternal dietary EPA and DHA supplementation and breeder age on
      embryonic and post-hatch performance of broiler offspring: age and n-3 pufa
      affect embryonic and post-hatch performance.
AB  - Breeder age and nutrition are amongst the most important factors affecting
      progeny growth and development. The present experiment was carried out to
      evaluate the effects of n-3 fatty acid (FA), with special emphasis on the ratio
      of eicosapentaenoic (EPA, 20:5 n-3) and docosahexaenoic (DHA, 22:6 n-3) acid,
      provided to the diet of ageing broiler breeder hens at different ratios, on the
      incubation parameters and the performance of the offspring. Four hundred and
      eighty Ross-308 broiler breeder hens were fed one of four different diets
      (120/treatment), with an equal fat content. The control diet was a basal diet,
      rich in n-6 FAs (CON). Blends of fish oil were used to enrich the three other
      diets in n-3 FA and to obtain different EPA/DHA ratios of 1/1 (EPA=DHA), 1/2
      (DHA) or 2/1 (EPA). Every 5 weeks, incubation parameters were assessed. Every 15
      weeks, offspring was reared until slaughter age on a standard diet. Breeder age
      affected almost all incubation and post-hatch parameters, whereas n-3 FA
      treatment only lowered egg weight (p < 0.0001) and consequently hatched chick
      weight (p < 0.0001). Supplementation of EPA resulted in a higher proportional
      liver weight (p = 0.0219) at hatch, a lower body weight up to 28 days post-hatch
      (p = 0.0418), a lower daily weight gain (p = 0.0498) and a higher feed conversion
      ratio (p = 0.0395) during the starter period (p = 0.0498), resulting in a higher
      overall offspring feed conversion ratio (p = 0.0317) compared to the control
      diet. DHA supplementation, on the other hand, resulted in a lower residual yolk
      weight (p = 0.0220) and a higher overall offspring mortality (p = 0.0125). In
      conclusion, supplementation of n-3 FA could not counter the adverse effect of
      breeder flock age, but did not harm incubation or improve post-hatch performance,
      either. EPA and DHA affected offspring development differently during early post
      hatch life.

PMID- 25865422
TI  - Evaluation of the use of esterified fatty acid oils enriched in medium-chain
      fatty acids in weight loss diets for dogs.
AB  - Esterified fatty acid oils (EAOs) are obtained from esterification of vegetable
      acid oils with glycerol. These fat sources have the same fatty acid (FA)
      composition as their respective native oils but new chemical properties. Several
      studies have confirmed the potential of medium-chain fatty acids (MCFA) to reduce
      fat mass (FM) in humans and rodents. This study investigates the use of EAOs with
      different MCFA proportions on food preferences, digestibility and weight loss
      management in dogs. A basal diet was supplemented with 8% of three different fat
      sources: C0: soya bean-canola EAO, C20: soya bean-canola (80%) coconut (20%) EAO
      and C40: soya bean-canola (60%) coconut (40%) EAO. Food preference of these EAOs
      was tested using a two-pan preference test. Dogs presented a higher daily food
      intake of C20 and C40 compared to C0 (C20: 155 +/- 18.6 g vs. C0: 17 +/- 7.0 g, p
      < 0.001; C40: 117 +/- 13.9 g vs. C0: 28 +/- 10.5 g, p < 0.05 respectively). Also,
      the digestibility of the three experimental diets was tested. C20 and C40 showed
      higher ether extract, total FA and saturated FA digestibilities (p < 0.05) than
      C0 diet. Lastly, the three diets were investigated in a 14-week weight loss
      study, following 16 weeks of ad libitum feeding to induce overweight condition.
      Body weight (BW) reduction was lower (C0: 20.1 +/- 2.32%, C20: 14.6 +/- 1.43% and
      C40: 15.7 +/- 1.23%, p < 0.05) and FM was higher (FM, 18.7 +/- 3.42%, 27.9 +/-
      3.90% and 28.2 +/- 2.88% for C0, C20 and C40, respectively, p < 0.05) for diets
      C20 and C40 than for C0. Feeding diets with MCFA at these inclusion levels to
      experimentally overweight dogs during 14 weeks do not result in faster weight
      loss compared to unsaturated long-chain FA.

PMID- 25865426
TI  - The pharmacokinetic/pharmacodynamic rationale for administering vancomycin via
      continuous infusion.
AB  - WHAT IS KNOWN AND OBJECTIVE: Vancomycin is administered via intermittent infusion
      (II) almost exclusively in the United States, whereas continuous infusion (CI)
      dosing methods are used regularly in many European countries. The purpose of this
      literature analysis is to review current evidence regarding the advantages and
      disadvantages of CI vancomycin in relation to II, based on the pharmacokinetic
      and pharmacodynamic aspects of dosing and monitoring therapy, and to identify
      current practices of CI vancomycin dosing. METHODS: Medline, Cochrane and
      GoogleScholar databases were searched using vancomycin as a MeSH term, along with
      continuous and infusion in all fields, which identified 136 citations. A second
      search added the terms intermittent and survey, producing nine additional
      articles. All articles that reported an assessment of CI or II vancomycin
      administration in adult patients, based on clinical, pharmacokinetic, cost or
      monitoring considerations, were identified. A total of 43 publications were
      determined to be suitable for final analysis and possible inclusion in the
      report. RESULTS AND DISCUSSION: A meta-analysis of six studies concluded that CI
      vancomycin was associated with a lower relative risk of kidney injury than II
      therapy, although other studies reported equivocal findings. The results of
      several clinical studies suggest that CI vancomycin produces clinical outcomes
      that are comparable to II. Current vancomycin consensus guidelines promote
      aggressive dosing to achieve trough levels of 10-15 or 15-20 mg/L, but also
      include recommendations to target a daily area under the curve (AUC24 ) to
      minimum inhibitory concentration (MIC) ratio of at least 400. Because vancomycin
      is a non-concentration-dependent antibiotic, it might be more prudent to monitor
      steady-state serum concentrations (Css ) during a CI rather than trough
      concentrations during II, due to the questionable correlation between measured
      trough concentration and AUC. From a pharmacokinetic/pharmacodynamic perspective,
      vancomycin dosing and monitoring practices associated with CI offer potentially
      greater reliability than II. A major disadvantage of CI involves the possibility
      of having to intravenously co-administer another drug that might not be
      compatible with vancomycin. WHAT IS NEW AND CONCLUSION: Continuous infusion
      vancomycin therapy offers the advantage of Css monitoring, thus avoiding the
      variabilities associated with the timing of trough levels. Current CI practices
      include a loading dose of 15-20 mg/kg followed by an infusion of 10-40 mg/kg/day
      based on the patient's renal function, with a target Css of about 20-30 mg/L. An
      alternative approach to weight-based (mg/kg) CI dosing is to calculate the dose
      from an estimation of the patient's vancomycin clearance (in L/h), derived from
      creatinine clearance (CrCl) via the equation (CrCl?0.041) + 0.22. The daily dose
      is then determined by multiplying vancomycin clearance (in L/h) by the desired
      AUC24 . A new CI vancomycin dosing chart includes clearance-based dosing
      recommendations for Css values ranging from 17.5 to 27.5 mg/L or AUC24 values
      ranging from 420 to 660 mg h/L. Although sufficient data already exist to support
      the use of CI vancomycin as a reasonable therapeutic alternative to II, there is
      still much to learn about administering the drug in this fashion.

PMID- 25865427
TI  - [Complementary feeding: Evolving concepts and recommendations].

PMID- 25865429
TI  - Measuring induction times and crystal nucleation rates.
AB  - A large variation is observed in induction times measured under equal conditions
      in 1 ml solutions. Ruling out experimental errors, this variation originates from
      the nucleation process. The induction time distribution is explained by the
      stochastic nature of nucleation if the number of nuclei formed is approaching 1
      per vial. Accurate heterogeneous crystal nucleation rates were determined from
      the induction time distributions on a 1 ml scale for racemic diprophylline in two
      solvents. The difference in nucleation behaviour in the two solvents originates
      from the energy barrier for nucleation, which is much higher in the solvent in
      which induction times are much longer. In addition the pre-exponential factor for
      the crystal nucleation rate in both solvents is rather low compared to
      predictions using Classical Nucleation Theory. Unfortunately, concentration and
      surface characteristics of the effective heterogeneous particles are not known
      which clouds a further molecular interpretation. 

PMID- 25865428
TI  - Urinary mRNA levels of ELR-negative CXC chemokine ligand and extracellular matrix
      in diabetic nephropathy.
AB  - BACKGROUND: Inflammation and fibrosis play important roles in the progression of
      diabetic nephropathy. We determine the urinary mRNA levels of ELR-CXC chemokine
      ligand and extracellular matrix in diabetic nephropathy. METHODS: We studied 26
      patients with biopsy-proven diabetic nephropathy, 15 with hypertensive
      nephrosclerosis and 10 healthy controls. Urinary mRNA levels of CXCL9, CXCL10,
      CXCL11, collagen I A1 chain, collagen IV A3 chain and fibronectin were measured.
      Patients were followed for 36.9 +/- 7.4 months to determine the rate of
      glomerular filtration rate (GFR) decline. RESULTS: Urinary mRNA levels of CXCL10
      and CXCL11 are decreased, and those of collagen I A1 chain and fibronectin are
      increased in diabetic nephropathy. Baseline estimated GFR correlates with urinary
      mRNA level of CXCL9 (r = 0.583, p = 0.002) and CXCL11 (r = 0.703, p < 0.0001),
      respectively. The rate of GFR decline significantly correlates with urinary CXCL9
      (r = -0.618, p = 0.0008) and CXCL11 mRNA levels (r = -0.726, p < 0.0001).
      Multivariate linear regression analysis confirms that urinary CXCL9 mRNA level is
      independently associated with the rate of GFR decline, while the correlation with
      urinary CXCL11 mRNA level has borderline significance. CONCLUSION: Urinary CXCL9
      and CXCL11 mRNA levels correlate with baseline renal function. The rate of renal
      function decline correlates with urinary CXCL9 mRNA level. Our results suggest
      that urinary CXCL9 mRNA levels may be used for risk stratification of diabetic
      nephropathy.

PMID- 25865430
TI  - An In Vitro Comparison of Fracture Load of Zirconia Custom Abutments with
      Internal Connection and Different Angulations and Thicknesses: Part II.
AB  - PURPOSE: The purpose of part II of this in vitro study was to compare the
      fracture load of two-piece zirconia custom abutments with different thicknesses
      and angulations. MATERIALS AND METHODS: Forty zirconia custom abutments were
      divided into four groups as follows: group A1: 0.7 mm thickness and 0 degrees 
      angulations; group A2: 0.7 mm thickness and 15 degrees  angulations; group B1: 1
      mm thickness and 0 degrees  angulations; group B2: 1 mm thickness and 15 degrees 
      angulations. As in part I, in all groups, implant replicas were mounted in self
      cure acrylic jigs to support the abutments. The zirconia custom abutments were
      engaged in the implant replicas using a manual torque wrench. All jigs were
      secured and mounted in a metallic vice and subjected to shear stress till failure
      using a universal testing machine with a 0.5 mm/min crosshead speed with the
      force transferred to the lingual surface of the zirconia custom abutments 2 mm
      below the incisal edge. The test specimens used in this study did not include a
      crown. The universal testing machine was controlled via a computer software
      system, which also completed the stress-strain diagram and recorded the breaking
      fracture load. The fracture loads were recorded for comparison among the groups
      and subjected to statistical analysis (two-way ANOVA and Kolmogorov-Smirnov).
      RESULTS: The mean fracture load of zirconia custom abutments across the groups
      (A1 to B2) ranged from 432 +/- 97 N to 746 +/- 275 N. The angulated zirconia
      custom abutment exhibited the highest fracture load, which was statistically
      significant (p = 0.045). The thickness of the zirconia custom abutment also had a
      positive influence on the strength of the specimens (p = 0.005). CONCLUSIONS: In
      this study, the 15 degrees  angulated zirconia custom abutments showed the
      highest fracture load of those investigated. The 1 mm thick zirconia custom
      abutments also exhibited significantly higher fracture load compared to 0.7 mm
      abutments. CLINICAL IMPLICATIONS: The results of this in vitro study will help
      dental practitioners with their decision-making process in selecting the type of
      custom abutment to be used clinically.

PMID- 25865431
TI  - Improving Service Utilization for Parents with Substance Abuse Problems:
      Experimenting with Recovery Coaches in Child Welfare.
AB  - Substance abusers often face substantial systematic and personal barriers to
      receiving required substance abuse treatment services as well as other services;
      hence, various linkage mechanisms have been proposed for drug abuse treatment
      programs to overcome such barriers. Although there is a growing interest in the
      use of case management with a substance abuse background, its effectiveness in
      child welfare has yet to be explored. In this study the author attempts to
      investigate the effectiveness of case management in service utilization by
      systematically evaluating the five-year Alcohol and Other Drug Abuse (AODA)
      waiver demonstration project with Recovery Coaches in Illinois. A classic
      experimental design with a control group was used. Random assignment occurs at
      the agency level. Parents in the experimental group (N = 1562) received recovery
      coaches in addition to traditional child welfare services while parents in the
      control group (N = 598) only received traditional child welfare services.
      Bivariate and multivariate analyses (Ordinary Last Square regressions) were used.
      Compared to parents in the control group, parents in the experimental group were
      more likely to utilize substance abuse treatment. The results suggest that
      gender, education level, employment status, and the number of service needs were
      significantly associated with service utilization. Controlling other factors,
      recovery coaches improved overall service utilization. Because the outcome of
      child welfare often depends on the improvement of risks or resolution, it is
      important for parents to utilize the needed services. Future studies need to
      address what aspects of recovery coaches facilitate the services utilization. 

PMID- 25865432
TI  - Characterization of multidrug transporter-mediated efflux of avermectins in human
      and mouse neuroblastoma cell lines.
AB  - ABC transporters play an important role in the disposition of avermectins in
      several animal species. In this study the interactions of three key avermectins,
      abamectin, emamectin and ivermectin, with human and mouse homologues of MDR1
      (ABCB1/Abcb1a) and MRP (ABCC/Abcc), transporters endogenously expressed by human
      SH-SY5Y and mouse N2a neuroblastoma cells were investigated. In both cell lines,
      retention of the fluorescent dye H33342 was found to be significantly increased
      in the presence of avermectins and cyclosporin A. These effects were shown to be
      unresponsive to the BCRP inhibitor Ko-143 and therefore MDR1/Mdr1-dependent.
      Avermectins inhibited MDR1/Mdr1a-mediated H33342 dye efflux, with apparent Ki
      values of 0.24+/-0.08 and 0.18+/-0.02MUM (ivermectin); 0.60+/-0.07 and 0.56+/
      0.02MUM (emamectin) and 0.95+/-0.08 and 0.77+/-0.25MUM (abamectin) in SH-SY5Y and
      N2a cells, respectively. There were some apparent affinity differences for MDR1
      and Mdr1a within each cell line (affinity for ivermectin>emamectin>=abamectin,
      P<0.05 by One-Way ANOVA), but importantly, the Ki values for individual
      avermectins for human MDR1 or mouse Mdr1a were not significantly different. MK571
      sensitive retention of GSMF confirmed the expression of MRP/Mrp efflux
      transporters in both cell lines. Avermectins inhibited MRP/Mrp-mediated dye
      efflux with IC50 values of 1.58+/-0.51 and 1.94+/-0.72MUM (ivermectin); 1.87+/
      0.57 and 2.74+/-1.01MUM (emamectin) and 2.25+/-0.01 and 1.68+/-0.63MUM
      (abamectin) in SH-SY5Y and N2a cells, respectively. There were no significant
      differences in IC50 values between individual avermectins or between human MRP
      and mouse Mrp. Kinetic data for endogenous human MDR1/MRP isoforms in SH-SY5Y
      cells and mouse Mdr1a/b/Mrp isoforms in N2a cells are comparable for the selected
      avermectins. All are effluxed at concentrations well above 0.05-0.1MUM ivermectin
      detected in plasma (Ottesen and Campbell, 1994; Ottesen and Campbell, 1994) This
      is an important finding in the light of toxicity seen in the Mdr1-deficient
      animal models CF-1 mice, Mdr1ab (-/-) double knockout mice and Collie dogs. We
      also confirm MRP/Mrp-mediated avermectin transport in both N2a and SH-SY5Y cell
      lines.

PMID- 25865433
TI  - Predicting long-term weight loss maintenance in previously overweight women: a
      signal detection approach.
AB  - OBJECTIVE: Examine psychological and behavioral predictors of 3-year weight loss
      maintenance in women. METHODS: Participants were 154 women in a 1-year randomized
      controlled trial on weight management with a 2-year follow-up. Signal detection
      analyses identified behavioral and psychological variables that best predicted 5%
      and 10% weight loss at 3 years. RESULTS: Women with better body image were more
      likely to have lost >=5% weight at 3 years (P < 0.001). Exercise intrinsic
      motivation had a partial compensatory effect, in that women with poor body image
      but higher motivation were more likely to maintain weight loss than women with
      poor body image and lower motivation (P < 0.001). Women with high exercise
      autonomous motivation were three times more likely to have lost >=10% weight than
      were those with lower autonomous motivation (P < 0.001). Among women with lower
      autonomous motivation, perceiving fewer exercise barriers was somewhat
      compensatory: these women were more likely to maintain weight loss than women
      with lower autonomy but more perceived barriers (P < 0.01). CONCLUSIONS: In
      overweight women, improving body image and increasing autonomous and intrinsic
      motivation for exercise likely promotes clinically significant long-term weight
      loss maintenance. Decreasing perceived exercise barriers is another promising
      intervention target.

PMID- 25865434
TI  - Optimizing repeat liver transplant graft utility through strategic matching of
      donor and recipient characteristics.
AB  - Repeat liver transplantation (LT) is controversial because of inferior outcomes
      versus primary LT. A minimum 1-year expected post-re-LT survival of 50% has been
      proposed. We aimed to identify combinations of Model for End-Stage Liver Disease
      (MELD), donor risk index (DRI), and recipient characteristics achieving this
      graft survival threshold. We identified re-LT recipients listed in the United
      States from March 2002 to January 2010 with > 90 days between primary LT and
      listing for re-LT. Using Cox regression, we estimated the expected probability of
      1-year graft survival and identified combinations of MELD, DRI, and recipient
      characteristics attaining >50% expected 1-year graft survival. Re-LT recipients
      (n = 1418) had a median MELD of 26 and median age of 52 years. Expected 1-year
      graft survival exceeded 50% regardless of MELD or DRI in Caucasian recipients who
      were not infected with hepatitis C virus (HCV) of all ages and Caucasian HCV
      infected recipients <50 years old. As age increased in HCV-infected Caucasian and
      non-HCV-infected African American recipients, lower MELD scores or lower DRI
      grafts were needed to attain the graft survival threshold. As MELD scores
      increased in HCV-infected African American recipients, lower-DRI livers were
      required to achieve the graft survival threshold. Use of high-DRI livers (>1.44)
      in HCV-infected recipients with a MELD score > 26 at re-LT failed to achieve the
      graft survival threshold with recipient age >= 60 years (any race), as well as at
      age >= 50 years for Caucasians and at age < 50 years for African Americans.
      Strategic donor selection can achieve >50% expected 1-year graft survival even in
      high-risk re-LT recipients (HCV infected, older age, African American race, high
      MELD scores). Low-risk transplant recipients (age < 50 years, non-HCV-infected)
      can achieve the survival threshold with varying DRI and MELD scores.

PMID- 25865436
TI  - Identification of UV-Induced Diterpenes Including a New Diterpene Phytoalexin,
      Phytocassane F, from Rice Leaves by Complementary GC/MS and LC/MS Approaches.
AB  - Rice phytoalexins are regarded as one of the most important weapons against
      pathogenic microorganisms. We attempted to identify novel phytoalexins and their
      derivatives using GC/MS and LC/MS analyses. Diterpene derivatives, 9beta-pimara
      7,15-diene-3beta,6beta,19-triol, 1, stemar-13-en-2alpha-ol, 2, and 1alpha,2alpha
      dihydroxy-ent-12,15-cassadiene-3,11-dione, 3, were isolated from UV-irradiated
      rice leaves by chromatographic methods. These structures were confirmed by 1D-
      and 2D-NMR and MS analyses. Interestingly, all three compounds were accumulated
      following an infection by the rice blast pathogen Magnaporthe oryzae. Compounds 1
      and 2 exhibited weak antifungal activity and may be the biosynthetic
      intermediates of rice phytoalexins momilactones and oryzalexin S, respectively.
      Compound 3 exhibited relatively high inhibitory activity against the fungal
      mycelial growth of M. oryzae to the same extent as the known phytoalexin
      phytocassane A. We conclude that 3 is a member of the cassane-type phytoalexin
      family and propose the name phytocassane F. 

PMID- 25865435
TI  - Prone Versus Supine Breast FDG-PET/CT for Assessing Locoregional Disease
      Distribution in Locally Advanced Breast Cancer.
AB  - RATIONALE AND OBJECTIVES: Prone (18)F fluorodeoxyglucose positron emission
      tomography/computed tomography (FDG-PET/CT) may have advantages for breast
      imaging because of improved separation of deep anatomic structures. There are
      limited data on whether prone and supine FDG-PET/CT provide similar information
      regarding breast and axillary disease in the setting of locally advanced breast
      cancer (LABC). The purpose of this study was to compare the information on
      locoregional disease distribution provided by prone versus supine FDG-PET in
      newly diagnosed LABC. MATERIALS AND METHODS: In an Institutional Review Board
      approved prospective trial, 24 patients with newly diagnosed LABC underwent both
      supine and prone FDG-PET/CT at the same scanning session. Three readers performed
      an independent review of all scans and categorized the locoregional disease
      distribution as breast only (BO)-unifocal, BO-multifocal, BO-multicentric, or
      breast + axillary involvement. For breast + axillary disease, the readers also
      assessed the number of involved axillary lymph nodes. Interobserver discrepancies
      were resolved at a consensus reading session. RESULTS: Two scanning sessions were
      excluded because the prone scan had omitted part of the axilla from the field of
      view. In the remaining 22 patients, the consensus categorization of anatomic
      disease distribution was concordant between prone and supine scanning in 21
      patients (linear kappa 0.91, 95% confidence interval [0.79-1]). In the 16
      patients with breast + axillary disease, equal numbers of involved lymph nodes
      were identified on prone and supine scanning in 12 patients, whereas in the
      remaining four patients, prone scanning resulted in a higher number of visualized
      lymph nodes. CONCLUSIONS: Prone and supine FDG-PET/CT provided statistically
      identical information on locoregional disease distribution in LABC. However,
      prone scanning may perform better than supine for assessing the number of
      involved lymph nodes. Prone FDG-PET/CT may be useful in future clinical and
      research efforts, including hybrid PET-magnetic resonance imaging (MRI)
      applications.

PMID- 25865437
TI  - Audit of the Functioning of the Elective Neurosurgical Operation Theater in
      India: A Prospective Study and Review of Literature.
AB  - BACKGROUND: Knowledge about the utilization of the operation theater (OT) is
      essential to improve its efficiency. This study evaluated the neurosurgical
      operation theater utilization in a neurosciences teaching hospital. METHODS: Data
      collected included OT start time, delay in start, anesthesia induction time,
      surgical preparation time, anesthesia recovery time, operating time, time between
      cases, and theater closing time. RESULTS: Five hundred thirty-seven surgeries
      were performed during the study period. The percentage of time used for
      anesthesia induction, actual surgical procedure, recovery from anesthesia, and
      theater preparation between the two cases were 8%, 70%, 6% and 5%, respectively.
      Fourteen percent of scheduled cases were cancelled. On 220 occasions (70.51%),
      theater was over-run. Late start contributed to loss of 8370 minutes (140 hours)
      of theater time. CONCLUSIONS: This study identified the proportion of time spent
      on each activity in the neurosurgical OT. This knowledge is likely to facilitate
      better planning of neurosurgical theater schedule and result in optimal
      utilization.

PMID- 25865438
TI  - A Weibull multi-state model for the dependence of progression-free survival and
      overall survival.
AB  - In oncology clinical trials, overall survival, time to progression, and
      progression-free survival are three commonly used endpoints. Empirical
      correlations among them have been published for different cancers, but
      statistical models describing the dependence structures are limited. Recently,
      Fleischer et al. proposed a statistical model that is mathematically tractable
      and shows some flexibility to describe the dependencies in a realistic way, based
      on the assumption of exponential distributions. This paper aims to extend their
      model to the more flexible Weibull distribution. We derived theoretical
      correlations among different survival outcomes, as well as the distribution of
      overall survival induced by the model. Model parameters were estimated by the
      maximum likelihood method and the goodness of fit was assessed by plotting
      estimated versus observed survival curves for overall survival. We applied the
      method to three cancer clinical trials. In the non-small-cell lung cancer trial,
      both the exponential and the Weibull models provided an adequate fit to the data,
      and the estimated correlations were very similar under both models. In the
      prostate cancer trial and the laryngeal cancer trial, the Weibull model exhibited
      advantages over the exponential model and yielded larger estimated correlations.
      Simulations suggested that the proposed Weibull model is robust for data
      generated from a range of distributions.

PMID- 25865439
TI  - Facile hydrolysis and alcoholysis of palladium acetate.
AB  - Palladium(II) acetate is readily converted into [Pd3 (MU(2) -OH)(OAc)5 ] (1) in
      the presence of water in a range of organic solvents and is also slowly converted
      in the solid state. Complex 1 can also be formed in nominally anhydrous solvents.
      Similarly, the analogous alkoxide complexes [Pd3 (MU(2) -OR)(OAc)5 ] (3) are
      easily formed in solutions of palladium(II) acetate containing a range of
      alcohols. An examination of a representative Wacker-type oxidation shows that the
      Pd-OH complex 1 and a related Pd-oxo complex 4 can be excluded as potential
      catalytic intermediates in the absence of exogenous water. 

PMID- 25865440
TI  - Rates of recurrent variceal bleeding are low with modern esophageal banding
      strategies: a retrospective cohort study.
AB  - BACKGROUND: Variceal bleeding has a high rate of mortality and recurrence.
      Endoscopic band ligation (EBL) is the established standard of care for secondary
      prevention of variceal bleeding. OBJECTIVE: To determine the long-term re
      bleeding rate of an EBL protocol similar to current society guidelines. DESIGN:
      We conducted a retrospective cohort study at a tertiary care center of all
      patients with a history of a variceal bleed who underwent an aggressive band
      ligation protocol. INTERVENTIONS: At the time of sentinel bleed, all varices,
      regardless of size, were ligated. EBL was then repeated every 2 weeks until
      stabilization, and all visible varices were ligated. The interval between banding
      sessions then increased. MAIN OUTCOME MEASUREMENTS: The incidence of re-bleeding
      was calculated as the time between clinical stabilization after the sentinel
      event until data censoring, which occurred at time of re-bleed, death, transplant
      or loss-to-follow up. Gastric variceal bleeding was a secondary endpoint.
      RESULTS: N = 176 patients were treated with aggressive EBL, and followed for a
      median of 16 months (range, 3 months - 6.9 years). The 6 month incidence of re
      bleeding was 2.3%, the 12 month incidence was 3.4%, and the 2 year incidence was
      4.6%. Overall, aggressive EBL was well-tolerated. One patient died during follow
      up secondary to a gastric variceal bleed. CONCLUSIONS: Aggressive EBL yields a
      low rate of re-bleeding when compared to standard practice. Secondary prophylaxis
      with aggressive EBL should be a consideration for patients following a sentinel
      bleeding event.

PMID- 25865442
TI  - Youth violence: A review of risk factors, causal pathways and effective
      intervention.
AB  - This paper presents a review of theoretical and empirical research on risk
      factors for: 1) the development of violent and other antisocial behaviour; 2)
      international interventions targeting antisocial, including violent youths; and
      3) outcome evaluations and meta-analyses of interventions targeting antisocial,
      including violent youths. Taken together, the international literature indicates
      that interventions which effectively reduce violent and other antisocial
      behaviours are informed by a number of generic principles which should guide the
      development and implementation of South African violence-prevention programmes.
      Common characteristics of interventions which effectively reduce youth violence
      are presented, with the aim of informing the design and delivery of local
      interventions. In light of the alarmingly high levels of violence in South
      Africa, there is an urgent need to develop intensive, multi-modal, evidence
      based, structured, cognitive-behavioural programmes for violent adolescents and
      young adults. Furthermore, it is imperative that efforts are directed at
      developing a reliable local evidence base of 'what works' for young offenders
      generally, and violent young offenders specifically. 

PMID- 25865443
TI  - Long-term care of children and adolescents with intellectual disabilities and
      severe physical abnormalities.
AB  - OBJECTIVE: This study sets out to review the clinical profile and treatment
      program of children and adolescents with intellectual disability in Waverley Care
      Center (WCC). METHOD: A retrospective review was done of users from January to
      December 2004. Reviewed parameters included age, gender, length of stay, DSM IV
      diagnoses, current medical treatment, and level of functioning and mobility
      according to the Therapeutic Classification System for Children (TCS). RESULTS: A
      total of 179 users were receiving care. Although the mean age of users was 14 to
      15 years, their ages ranged from 3 to 34 years. The gender ratio of users was 1
      (female) to 1.6 (male). The average length of stay was 6.73 years and the range
      of stay from 0.5 to 29 years. Attention deficit hyperactivity disorder was
      diagnosed in eight children and pervasive disorders were suspected in some.
      Intellectual impairment ranged from severe to profound. Specific interventions
      with regard to severe physical impairments were made by occupational therapy and
      physiotherapy. CONCLUSION: Due to the extent of their physical disabilities
      requiring full-time nursing care, discharge and placement back in the community
      remained a rare option for most users in the study group.

PMID- 25865444
TI  - Use of the 1996 Griffiths Mental Development Scales for infants: a pilot study
      with a Black, South African sample.
AB  - OBJECTIVES: Over the last few years, researchers have made a significant effort
      to address the need for more reliable and valid assessment measures for South
      Africa. The objective of this study was to acquire empirical data regarding the
      use and application of the Griffiths Mental Development Scales with Black South
      African infants. METHODS: Specifically, the study aimed to make a preliminary
      cross-cultural comparison of the performance of Black South African infants and
      the British normative sample of the Griffiths Scales (Huntley 1996). The South
      African sample consisted of 40 infants aged between 13 and 16 months, with
      approximately equal numbers of boys and girls. RESULTS: The finding was that the
      South African sample performed significantly better than the British norm group
      on the Eye-Hand Co-ordination Scale (Scale D) and the Performance Scale (Scale
      E), while the norm group scored significantly higher on the Personal-Social Scale
      (Scale B). CONCLUSION: The implications of these results are discussed in the
      paper.

PMID- 25865441
TI  - Relationship between cortical thickness and cerebrospinal fluid YKL-40 in
      predementia stages of Alzheimer's disease.
AB  - Cerebrospinal fluid YKL-40 has been described as a marker of glial inflammation.
      We aimed to study the relationship between YKL-40 and brain structure and its
      interactions with core Alzheimer's disease (AD) biomarkers. We measured cortical
      thickness (CTh) and cerebrospinal fluid biomarkers (amyloid-beta 1-42 [Abeta42],
      total tau, p-tau, and YKL-40) of 80 cognitively normal controls and 27 patients
      with amnestic mild cognitive impairment. Subjects were classified as Abeta42+
      (<550 pg/mL) or Abeta42- (>550 pg/mL). CTh difference maps were derived from the
      interaction and correlation analyses in the whole sample and within clinical
      groups. There was a strong correlation between YKL-40 and markers of
      neurodegeneration (total tau and p-tau). In the whole sample, we found a negative
      correlation between YKL-40 and CTh in AD vulnerable areas in Abeta42+ subjects
      but not in Abeta42 participants. Our results suggest that YKL-40 could track the
      inflammatory processes associated to tau-related neurodegeneration in the
      presence of the AD pathophysiological process.

PMID- 25865445
TI  - Secondary school learners' essays on suicide prevention.
AB  - OBJECTIVES: Considering the extent of the problem of suicidal behaviour among
      young people, the need for prevention programmes is paramount. The KwaZulu-Natal
      based 'Love to Live' campaign is a programme aimed at the prevention of suicidal
      behaviour among children and adolescents. METHODS: The present study is an
      analysis of 63 essays written by secondary school learners on the subject of
      suicide prevention. RESULTS: Just over two-thirds of the essays revealed
      reasonable knowledge without serious inaccuracies, with over half the sample
      citing conflict with parents as precipitants to suicidal behaviour. Over one
      third of the essays blamed suicidal persons for being ineffective in dealing with
      their life problems, and over one-third identified mental health workers and
      parents as sources of help. CONCLUSIONS: The results are discussed in terms of
      adolescents' views of suicidal behaviour, as well as within the context of the
      limitations of the study methodology.

PMID- 25865446
TI  - Personality and criminal outcomes of homeless youth in a Nigerian jail
      population: results of PDS and MAACL-H assessments.
AB  - OBJECTIVE: The unprecedented incidence of armed robberies and the involvement of
      young people in these crimes necessitated - as part of a comprehensive study on
      homelessness and criminal behaviour in Nigeria - an assessmet and comparison of
      homeless youths incarcerated in prisons with a control group of non-prison and
      never-homeless youths from the general population using the Psychopathic Deviate
      Scale (PDS) and the Multiple Affect Adjective Checklist hostility subscale (MAACL
      H). METHOD: Through in-depth interviews using a questionnaire, data were
      collected from 100 randomly selected homeless inmates in three Nigerian medium
      security prisons aged 15 to 26 (mean = 17.2), and another 100 non-prison and
      never-homeless youths from the general population aged 15 to 31 (mean = 25.2).
      RESULTS: Hypothesis 1 showed a higher score on the PDS (mean = 29.3) and MAACL-H
      (mean = 21.7) among the homeless group than the non-prison and never homeless
      group (PDS mean = 21.2) and (MAACL-H = mean 12.5), (PDS (t = (98) = 6.62, p <
      .05) and MAACL-H (t = (98) = 21.7, p < .0001). The second hypothesis also showed
      a significant relationship between PDS and the type of crime committed by
      homeless inmates (F (2, 97) = 3.213; p < .05) and the direction of this
      relationship was higher for PDS and felony followed by misdemeanour offences (p <
      .05, LSD = 2.81). The MAACL-H did not reach an acceptable level of significance
      for type of crime. CONCLUSION: These findings have significant practical and
      theoretical implications for personality and criminal outcomes for homeless
      youths in prisons when compared with non-prison and never-homeless youths. The
      study also suggests the need for more research in this direction and a review of
      antiquated penal policies for children, while the effective roles of governments
      and non-governmental organisations were also stressed.

PMID- 25865448
TI  - Autism and early years practice. A guide for early years professionals, teachers
      and parents.

PMID- 25865447
TI  - Traumatic experiences of Kenyan secondary school students.
AB  - BACKGROUND: There is no information on the socio-demographic variations and
      determinants of Trauma and Post-Traumatic Stress Disorder (PTSD) in Kenyan
      adolescents. OBJECTIVES: To describe the traumatic experiences of Kenyan high
      school students and to determine the levels of Post-traumatic Stress Disorder
      (PTSD) among them, and in relation to sociodemographic variables. DESIGN: A cross
      sectional study of 1 110 students (629 males and 481 females), aged 12 to 26
      years, using self-administered questionnaires. METHOD: The students completed
      questionnaires on sociodemographic data followed by the Trauma Checklist and the
      Child PTSD Checklist. RESULTS: Being confronted with bad news was the most common
      type of trauma encountered in 66.7% of the subjects, followed by witnessing a
      violent crime and domestic violence; 23.2% and 16.5% of the subjects reported
      physical abuse and sexual abuse respectively. PTSD symptoms were common;
      avoidance and re-experiencing occurred in 75% of the students and hyperarousal
      was reported by over 50%. The number of traumatic events was positively
      correlated with the occurrence of PTSD. The prevalence of full PTSD was 50.5%,
      while partial PTSD was 34.8%. Male and female subjects were equally affected but
      the boarders were more affected (p < 0.05) and the differences between the
      schools were statistically significant (p = 0.000). CONCLUSIONS: Kenyan secondary
      school students commonly experience traumatic events and have high rates of PTSD.
      Further studies are needed to determine the implications of these findings for
      their health and performance in school. The coping mechanisms need to be
      delineated and interventions put in place. Long-term studies are required to
      determine the role of such events in the causation of mental illness.

PMID- 25865449
TI  - Issues in school violence research.

PMID- 25865451
TI  - The relevance of violence-prevention interventions in South African Schools.

PMID- 25865450
TI  - The changing paradigm: from inclusion to belonging.

PMID- 25865452
TI  - Efficacy and effectiveness of anti-HBV therapy with early withdrawal of HBIG
      prophylaxis to prevent HBV recurrence following liver transplantation.
AB  - INTRODUCTION: The traditional regimen for prophylaxis of hepatitis B recurrence
      post-liver transplantation is to use hepatitis B immune globulin (HBIG) along
      with oral antiviral therapy; however, it is unclear when it is safe to
      discontinue HBIG after certain time point and to maintain patients with only oral
      antiviral therapy. Several studies have suggested that maintenance with oral anti
      hepatitis B virus (HBV) therapy following short-term or no HBIG following the
      immediate post-transplantation period may also be safe and effective in
      prevention of HBV recurrence. AREAS COVERED: We reviewed relevant literature to
      determine the effectiveness of early withdrawal of HBIG after liver
      transplantation and its effect on prevention of HBV recurrence. We used PubMed to
      search for any studies that used HBIG-free or short-term HBIG protocols with
      continued anti-HBV therapy. Short-term is defined as 12 months or less, and it is
      an evolving concept as new data on shorter and shorter duration becomes
      available. Additionally, a mini-quantitative analysis of the studies was
      performed using studies that involved the use of entecavir and tenofovir as anti
      HBV therapy with or without HBIG. EXPERT OPINION: Patients who are considered low
      risk for HBV recurrence at the time of liver transplant may safely be able to
      utilize a short-term duration of HBIG with indefinite antiviral maintenance
      therapy afterwards, whereas high-risk patients will likely need long-term HBIG in
      combination with antiviral therapy.

PMID- 25865453
TI  - Trastuzumab emtansine in advanced human epidermal growth factor receptor 2
      positive breast cancer.
AB  - INTRODUCTION: Ado- trastuzumab emtansine (T-DM1) is a human epidermal growth
      factor receptor 2 (HER2)-targeted antibody-drug conjugate composed of
      trastuzumab, a stable linker (MCC), and the cytotoxic agent DM1 (derivative of
      maytansine; mertansine). T-DM1 retains the mechanisms of action of trastuzumab,
      but also acts as a, selectively delivered, tubulin inhibitor. Following antigen
      mediated binding to the tumor cell, T-DM1 is endocytosed and intracellularly
      catabolized resulting in the release of its cytotoxic moiety. AREAS COVERED: T
      DM1 has completed Phase III development and compared favorably with the
      lapatinib/capecitabine combination with a superior response rate (objective
      response rate [ORR]) and duration of response, longer duration of disease control
      (progression-free survival [PFS]), prolonged overall survival and improved
      tolerability and quality of life in patients with prior treatment with
      trastuzumab and a taxane. In a separate Phase III, T-DM1 was compared with any
      other chosen regimen in patients who had at least received two prior HER2
      directed therapies. T-DM1 nearly doubled PFS. EXPERT OPINION: T-DM1 (Kadcyla) has
      become the treatment of choice in second-line and beyond for patients with
      advanced HER2-expressing breast cancer.

PMID- 25865455
TI  - Molybdenum disulfide as a highly efficient adsorbent for non-polar gases.
AB  - Molybdenum disulfide (MoS2), a kind of graphene-like, two-dimensional material,
      has attracted great interest because of its unique properties and potential
      applications in electronics and sensors. In this paper, first-principle
      calculations and grand canonical Monte Carlo (GCMC) simulations are performed and
      used to show that the MoS2 layer is efficient at absorbing non-polar gases.
      Compared with the popular gas sorbents (metal organic frameworks and carbon-based
      materials), MoS2 has additional advantages, including large surface to volume
      ratio and tunable properties. The non-polar gas [carbon dioxide (CO2) and methane
      (CH4)] adsorption on the MoS2 layer with and without vacancies has been
      systematically studied. The perfect MoS2 shows little or no adsorption for CO2
      and CH4 molecules, but the MoS2 with a single S vacancy and double S vacancies
      exhibits an excellent adsorption ability for CO2 and CH4 gases. The adsorption
      energies were 65 kJ mol(-1) for CO2 and 47 kJ mol(-1) for CH4 (van der Waals-D2),
      respectively. An orbital coupling between the p orbital of the CO2 (or CH4)
      molecule and the d orbital of the Mo atom was observed. GCMC simulation results
      show that MoS2 with a single S vacancy could absorb 42.1 wt% of CO2 and 37.6 wt%
      of CH4 under a pressure of 80 bar at room temperature. The results given in this
      paper indicate that monolayer MoS2 with defects is a highly efficient absorbent
      for non-polar gases. 

PMID- 25865456
TI  - MR-detected changes in liver fat, abdominal fat, and vertebral bone marrow fat
      after a four-week calorie restriction in obese women.
AB  - PURPOSE: To determine changes in the bone marrow fat fraction (BMFF) in obesity
      after dietary intervention in comparison with changes in abdominal fat, liver
      fat, and serum lipids. MATERIALS AND METHODS: Twenty obese (BMI 34.92 +/- 3.8
      kg/m(2) ) women participated in a 4-week dietary intervention of 800 kcal/d plus
      additional vegetables. They underwent anthropometric and blood value measurements
      before and after the intervention. Abdominal 3T MRI was performed to measure
      changes in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT)
      volume and single-voxel magnetic resonance spectroscopy (MRS) to measure fat
      content changes in the liver and L5 vertebral body. RESULTS: The greatest
      relative change after dietary intervention was found in the liver (-40.3%),
      followed by VAT volume (-15.1%), serum lipids (-12.6 to -14.5%), and SAT volume (
      8.5%). There were no statistically significant changes in BMFF after dietary
      intervention (P = 0.39), but absolute changes in the BMFF were positively
      associated with SAT volume (r = 0.489) and negatively associated with nonadipose
      tissue volume (r = -0.493) before dietary intervention. CONCLUSION: Bone marrow
      behaves differently compared to SAT volume, VAT volume, liver fat, and serum
      lipids after a 4-week dietary intervention in obesity and BMFF changes depend on
      abdominal tissue volumes before intervention.

PMID- 25865457
TI  - Biosimilar: what it is not.
AB  - A biosimilar is a high quality biological medicine shown to be in essence the
      same as an original product. The European Medicines Agency (EMA) paved the way in
      the regulatory arena by creating a safeguarding framework for the development of
      biosimilars. Biosimilar is thus a regulatory term that alludes to the evidence
      based studies required to demonstrate such very high similarity. They are
      therefore not innovative products but the pathway laid down by the EMA for their
      approval represented a new paradigm. This has brought some confusion and has cast
      doubts among healthcare professionals about the scientific evidence behind their
      authorization. Many papers have been published to clarify the concept, and to
      reassure those professionals, but misconceptions frequently still arise.
      Unfortunately, this prevents biosimilars from deploying their full therapeutic
      added value. This paper is intended to approach those misconceptions from a new
      angle, by explaining what a biosimilar is not...and why. A biosimilar is neither
      a generic, nor an original product. It is not a biobetter or a 'stand-alone'.
      Therefore, it should not be managed as such therapeutically, commercially or from
      a healthcare policy viewpoint. The EMA's criteria were acknowledged by other
      agencies, but a significant regulatory gap with a vast majority of regulatory
      bodies still remains. This leaves room for the so-called non-original biologics
      (NOB), i.e. non-biosimilar biologics, to be launched in many regions. Raising
      awareness of what a biosimilar is and what it is not, will generate trust in
      biosimilars among healthcare professionals and will ultimately benefit patients. 

PMID- 25865458
TI  - Anodal transcranial direct current stimulation over premotor cortex facilitates
      observational learning of a motor sequence.
AB  - Motor skills, including complex movement sequences, can be acquired by observing
      a model without physical practice of the skill, a phenomenon known as
      observational learning. Observational learning of motor skills engages the same
      memory substrate as physical practice, and is thought to be mediated by the
      action observation network, a bilateral fronto-parietal circuit with mirror-like
      properties. We examined the effects of anodal transcranial direct current
      stimulation (tDCS) over premotor cortex, a key node of the action observation
      network, on observational learning of a serial response time task. Results showed
      that anodal tDCS during observation of the to-be-learned sequence facilitated
      reaction times in the subsequent behavioral test. The study provides evidence
      that increasing excitability of the action observation network during observation
      can facilitate later motor skill acquisition. 

PMID- 25865459
TI  - Programmed emulsions for sodium reduction in emulsion based foods.
AB  - In this research a microstructure approach to reduce sodium levels in emulsion
      based foods is presented. If successful, this strategy will enable reduction of
      sodium without affecting consumer satisfaction with regard to salty taste. The
      microstructure approach comprised of entrapment of sodium in the internal aqueous
      phase of water-in-oil-in-water emulsions. These were designed to destabilise
      during oral processing when in contact with the salivary enzyme amylase in
      combination with the mechanical manipulation of the emulsion between the tongue
      and palate. Oral destabilisation was achieved through breakdown of the emulsion
      that was stabilised with a commercially modified octenyl succinic anhydride (OSA)
      starch. Microstructure breakdown and salt release was evaluated utilising in
      vitro, in vivo and sensory methods. For control emulsions, stabilised with orally
      inert proteins, no loss of structure and no release of sodium from the internal
      aqueous phase was found. The OSA-starch microstructure breakdown took the initial
      form of oil droplet coalescence. It is hypothesised that during this coalescence
      process sodium from the internalised aqueous phase is partially released and is
      therefore available for perception. Indeed, programmed emulsions showed an
      enhancement in saltiness perception; a 23.7% reduction in sodium could be
      achieved without compromise in salty taste (p < 0.05; 120 consumers). This study
      shows a promising new approach for sodium reduction in liquid and semi-liquid
      emulsion based foods. 

PMID- 25865460
TI  - Considerations of positive body image across various social identities and
      special populations.
AB  - Although the study of body image has been dominated by a focus on negative
      aspects, recent research interest has turned towards positive body image. The
      purpose of the present paper is to provide an integrative review of empirical
      research on the positive body image of individuals across a range of social
      identities beyond the typical college student. In particular, the review focuses
      on research exploring age, culture, gender, and special populations. Overall, the
      review finds that positive body image seems to confer benefit and operate
      similarly across a range of populations, although it may be expressed uniquely in
      different contexts. These results contribute to a more complete account of
      positive body image, but also raise a number of important additional questions
      and challenges for future research. 

PMID- 25865461
TI  - MicroRNA 26a prolongs skin allograft survival and promotes regulatory T cell
      expansion in mice.
AB  - MicroRNA 26a (Mir-26a) has been reported to play functions in cellular
      differentiation, cell growth, cell apoptosis, and metastasis. However, the role
      of Mir-26a in transplant rejection has never been investigated. Full-thickness
      skin grafts 1-2 cm in diameter were obtained from the tail-skin CBA/J donor mice
      and transplanted onto the back of wild-type C57Bl/6 recipient mice. Vectors
      encoding pre-Mir-26a (LV-26a) and an empty lentiviral vector (LV-Con) delivered
      approximately 2 * 10(7) transforming units of recombinant lentivirus were
      injected to mice once through the tail vein. Mir-26a overexpression results in
      prolonged skin allograft survival (MST = 9.5 days in LV-Con mice; MST = 22 days
      in LV-26a mice. P < 0.01) and promoted regulatory T cells (Tregs) expansion. The
      prolonged skin allograft survival induced by LV-26a was abrogated by depletion of
      Tregs with anti-CD25 antibodies. Mir-26a significantly promoted IL-10 expression
      and suppressed the expression of IL-6, IL-17, and IFN-gamma. Furthermore, IL-6
      overexpression led to complete suppression of the Mir-26a-induced upregulation of
      Foxp3. The prolonged allograft survival induced by LV-Mir-26a was also completely
      abrogated by IL-6 overexpression. In conclusion, Mir-26a prolongs skin allograft
      survival and promotes Tregs expansion in part through inhibition of IL-6
      expression.

PMID- 25865462
TI  - Are Physicians Safely Prescribing Opioids for Chronic Noncancer Pain? A
      Systematic Review of Current Evidence.
AB  - BACKGROUND: With rising prescription of opioid medications for chronic noncancer
      pain (CNCP) in the past years, opioid abuse and overdose deaths have increased in
      parallel. To ensure adequate treatment outcomes and reduce the risks linked with
      the chronic use of opioids, practitioner's adherence to treatment guidelines is
      essential. This study summarizes published recommendations about the strategies
      to reduce the risks associated with the chronic use of opioids and evaluates the
      adherence of physicians to these recommendations. METHOD: A systematic literature
      search was undertaken in May 2014 using major databases. Studies were included if
      they examined the adherence of practitioners with at least one form of opioid
      risk reduction strategy. Benchmark guidelines cited in these studies were also
      reviewed. RESULTS: The search yielded 683 records, 14 of which were found to
      evaluate adherence of physicians to opioid risk reduction strategies. Nine
      benchmark guidelines were found. Almost all physicians consider opioid therapy
      only when other safer approaches have failed and do not prescribe opioids at
      doses greater than 200 mg/day of morphine equivalent. Unfortunately, less than
      50% assess pain intensity using a pain scale; they often consider transdermal
      fentanyl safe for opioid-naive patients and fail to discontinue opioids if they
      were ineffective in relieving patients' pain. CONCLUSIONS: Substantial practice
      and knowledge gaps were identified, including the use of pain scales and
      prescription of transdermal fentanyl in opioid-naive patients, which have
      important implications for patient's safety. Guidelines more practical to
      physicians' settings and further education of physicians are warranted.

PMID- 25865463
TI  - Encapsulating micro-nano Si/SiO(x) into conjugated nitrogen-doped carbon as
      binder-free monolithic anodes for advanced lithium ion batteries.
AB  - Silicon monoxide, a promising silicon-based anode candidate for lithium-ion
      batteries, has recently attracted much attention for its high theoretical
      capacity, good cycle stability, low cost, and environmental benignity. Currently,
      the most critical challenge is to improve its low initial coulombic efficiency
      and significant volume changes during the charge-discharge processes. Herein, we
      report a binder-free monolithic electrode structure based on directly
      encapsulating micro-nano Si/SiOx particles into conjugated nitrogen-doped carbon
      frameworks to form monolithic, multi-core, cross-linking composite matrices. We
      utilize micro-nano Si/SiOx reduced by high-energy ball-milling SiO as active
      materials, and conjugated nitrogen-doped carbon formed by the pyrolysis of
      polyacrylonitrile both as binders and conductive agents. Owing to the high
      electrochemical activity of Si/SiOx and the good mechanical resiliency of
      conjugated nitrogen-doped carbon backbones, this specific composite structure
      enhances the utilization efficiency of SiO and accommodates its large volume
      expansion, as well as its good ionic and electronic conductivity. The annealed
      Si/SiOx/polyacrylonitrile composite electrode exhibits excellent electrochemical
      properties, including a high initial reversible capacity (2734 mA h g(-1) with
      75% coulombic efficiency), stable cycle performance (988 mA h g(-1) after 100
      cycles), and good rate capability (800 mA h g(-1) at 1 A g(-1) rate). Because the
      composite is naturally abundant and shows such excellent electrochemical
      performance, it is a promising anode candidate material for lithium-ion
      batteries. The binder-free monolithic architectural design also provides an
      effective way to prepare other monolithic electrode materials for advanced
      lithium-ion batteries. 

PMID- 25865464
TI  - Conformal Cu2S-coated Cu2O nanostructures grown by ion exchange reaction and
      their photoelectrochemical properties.
AB  - Cuprous oxide Cu2O is a promising p-type semiconductor for photoelectrochemical
      (PEC) solar hydrogen generation because it has a suitable bandgap (Eg = 2.0-2.2
      eV) and a band alignment adapted to water reduction. In addition, metallic Cu is
      earth-abundant thus making Cu2O a low-cost material. However, the reduction
      potential of Cu2O into metallic Cu (0.47 V versus RHE) is lower than that of
      water which induces a severe instability under irradiation in a PEC cell.
      Therefore, our recent efforts focused on the growth of a protective overlayer on
      top of Cu2O in order to stabilize Cu2O when used as a photocathode in an aqueous
      electrolyte. Among potential protective materials cuprous sulphide Cu2S is
      another p-type semiconductor with a 1.2 eV bandgap and an appropriate energy
      level alignment with Cu2O that would allow electrons flowing to the interface. We
      present here an original and simple method aimed at protecting a compact layer
      (CL) or nanowires (NWs) of Cu2O with a Cu2S coating. Our method is based on the
      ions exchange reaction (IER) of O(2-) into S(2-) at the surface of Cu2O itself in
      a solution-containing Na2S as the sulphur source. The local surface IER implies
      the formation of a conformal and uniform coating independently on the starting
      Cu2O morphology, CLs or NWs. As expected, coating Cu2O photocathodes by a
      conformal Cu2S layer improves their stability and PEC performances. 

PMID- 25865465
TI  - Recombinant Newcastle disease viral vector expressing hemagglutinin or fusion of
      canine distemper virus is safe and immunogenic in minks.
AB  - Canine Distemper Virus (CDV) infects many carnivores and cause several high
      mortality disease outbreaks. The current CDV live vaccine cannot be safely used
      in some exotic species, such as mink and ferret. Here, we generated recombinant
      lentogenic Newcastle disease virus (NDV) LaSota expressing either envelope
      glycoproyein, heamagglutinine (H) or fusion protein (F), named as rLa-CDVH and
      rLa-CDVF, respectively. The feasibility of these recombinant NDVs to serve as
      live virus-vectored CD vaccine was evaluated in minks. rLa-CDVH induced
      significant neutralization antibodies (NA) to CDV and provided solid protection
      against virulent CDV challenge. On the contrast, rLa-CDVF induced much lower NA
      to CDV and fail to protected mink from virulent CDV challenge. Results suggest
      that recombinant NDV expressing CDV H is safe and efficient candidate vaccine
      against CDV in mink, and maybe other host species. 

PMID- 25865466
TI  - Brazilian meningococcal C conjugate vaccine: Scaling up studies.
AB  - Several outbreaks caused by Neisseria meningitidis group C have been occurred in
      different regions of Brazil. A conjugate vaccine for Neisseria meningitidis was
      produced by chemical linkage between periodate-oxidized meningococcal C
      polysaccharide and hydrazide-activated monomeric tetanus toxoid via a modified
      reductive amination conjugation method. Vaccine safety and immunogenicity tested
      in Phase I and II trials showed satisfactory results. Before starting Phase III
      trials, vaccine production was scaled up to obtain industrial lots under Good
      Manufacture Practices (GMP). Comparative analysis between data obtained from
      industrial and pilot scales of the meningococcal C conjugate bulk showed similar
      execution times in the scaling up production process without significant losses
      or alterations in the quality attributes of purified compounds. In conclusion,
      scale up was considered satisfactory and the Brazilian meningococcal conjugate
      vaccine production aiming to perform Phase III trials is feasible. 

PMID- 25865467
TI  - Estimating the costs of the vaccine supply chain and service delivery for
      selected districts in Kenya and Tanzania.
AB  - Having data on the costs of the immunization system can provide decision-makers
      with information to benchmark the costs when evaluating the impact of new
      technologies or programmatic innovations. This paper estimated the supply chain
      and immunization service delivery costs and cost per dose in selected districts
      in Kenya and Tanzania. We also present operational data describing the supply
      chain and service delivery points (SDPs). To estimate the supply chain costs, we
      collected resource-use data for the cold chain, distribution system, and health
      worker time and per diems paid. We also estimated the service delivery costs,
      which included the time cost of health workers to provide immunization services,
      and per diems and transport costs for outreach sessions. Data on the annual
      quantities of vaccines distributed to each facility, and the occurrence and
      duration of stockouts were collected from stock registers. These data were
      collected from the national store, 2 regional and 4 district stores, and 12 SDPs
      in each country for 2012. Cost per dose for the supply chain and immunization
      service delivery were estimated. The average annual costs per dose at the SDPs
      were $0.34 (standard deviation (s.d.) $0.18) for Kenya when including only the
      vaccine supply chain costs, and $1.33 (s.d. $0.82) when including immunization
      service delivery costs. In Tanzania, these costs were $0.67 (s.d. $0.35) and
      $2.82 (s.d. $1.64), respectively. Both countries experienced vaccine stockouts in
      2012, bacillus Calmette-Guerin vaccine being more likely to be stocked out in
      Kenya, and oral poliovirus vaccine in Tanzania. When stockouts happened, they
      usually lasted for at least one month. Tanzania made investments in 2011 in
      preparation for planned vaccine introductions, and their supply chain cost per
      dose is expected to decline with the new vaccine introductions. Immunization
      service delivery costs are a significant portion of the total costs at the SDPs. 

PMID- 25865468
TI  - First clinical results of a personalized immunotherapeutic vaccine against
      recurrent, incompletely resected, treatment-resistant glioblastoma multiforme
      (GBM) tumors, based on combined allo- and auto-immune tumor reactivity.
AB  - Glioblastoma multiforme (GBM) patients have a poor prognosis. After tumor
      recurrence statistics suggest an imminent death within 1-4.5 months. Supportive
      preclinical data, from a rat model, provided the rational for a prototype
      clinical vaccine preparation, named Gliovac (or ERC 1671) composed of autologous
      antigens, derived from the patient's surgically removed tumor tissue, which is
      administered together with allogeneic antigens from glioma tissue resected from
      other GBM patients. We now report the first results of the Gliovac treatment for
      treatment-resistant GBM patients. Nine (9) recurrent GBM patients, after standard
      of care treatment, including surgery radio- and chemotherapy temozolomide, and
      for US patients, also bevacizumab (AvastinTM), were treated under a compassionate
      use/hospital exemption protocol. Gliovac was given intradermally, together with
      human GM-CSF (Leukine((r))), and preceded by a regimen of regulatory T cell
      depleting, low-dose cyclophosphamide. Gliovac administration in patients that
      have failed standard of care therapies showed minimal toxicity and enhanced
      overall survival (OS). Six-month (26 weeks) survival for the nine Gliovac
      patients was 100% versus 33% in control group. At week 40, the published overall
      survival was 10% if recurrent, reoperated patients were not treated. In the
      Gliovac treated group, the survival at 40 weeks was 77%. Our data suggest that
      Gliovac has low toxicity and a promising efficacy. A phase II trial has recently
      been initiated in recurrent, bevacizumab naive GBM patients (NCT01903330). 

PMID- 25865469
TI  - Construction of a triple gene-deleted Chinese Pseudorabies virus variant and its
      efficacy study as a vaccine candidate on suckling piglets.
AB  - New-emerging variants of Pseudorabies virus (PRV) compromise the protection
      provided by current vaccines and cause the death of all ages of vaccinated pigs
      since 2011. New vaccines based on current circulating PRV strain are needed to
      control the spread of disease since the variants are antigenically different from
      classical strains of virus. In this study, a TK/gE/gI triple gene-deleted PRV
      derived from current circulating field isolate was generated by using bacterial
      artificial chromosome techniques, and the rescued virus showed similar growth
      properties in vitro to its parent strain but reduced plaque size. To evaluate it
      as vaccine candidate, 9 day-old pigs were vaccinated and challenged with a
      virulent PRV variant. The results showed that vaccination can generate high level
      of protective gB-specific antibodies after vaccination and provide complete
      protection to the viral challenge. By contrast, the unvaccinated piglets all died
      within 6 days after viral challenge. Therefore, the TK/gE/gI triple gene-deleted
      PRV could be a promising vaccine candidate to control the wide spreading of PR
      variants in China. 

PMID- 25865470
TI  - Adjuvant activity of fish type I interferon shown in a virus DNA vaccination
      model.
AB  - There is a need for more efficient vaccines to combat viral diseases of Atlantic
      salmon and other farmed fish. DNA vaccines are highly effective against salmonid
      rhabdoviruses, but have shown less effect against other viruses. In the present
      work we have studied if type I IFNs might be used as adjuvants in fish DNA
      vaccines. For this purpose we chose a DNA vaccine model based on the
      hemagglutinin-esterase (HE) gene of infectious salmon anemia virus (ISAV) as
      antigen. Salmon presmolts were injected with a plasmid encoding HE alone or
      together with a plasmid encoding Atlantic salmon type I IFN (IFNa1, IFNb or
      IFNc). Sera were harvested after 7-10 weeks for measurements of antibody against
      ISAV and the fish were challenged with ISAV to measure protective effects of the
      vaccines. The results showed that all three IFN plasmids delivered together with
      HE plasmid potently enhanced protection of salmon against ISAV mediated mortality
      and stimulated an increase in IgM antibodies against the virus. In contrast, HE
      plasmid alone gave low antibody titers and a minor protection against ISAV. This
      demonstrates that type I IFNs stimulate adaptive immune responses in fish, which
      may be a benefit also in other fish DNA vaccines. Quantitative RT-PCR studies
      showed that the salmon IFNs caused an increased influx of B-cells and cytotoxic T
      cells at the muscle injection site, which may in part explain the adjuvant effect
      of the IFNs. 

PMID- 25865471
TI  - Subpopulations in aMPV vaccines are unlikely to be the only cause of reversion to
      virulence.
AB  - Avian metapneumovirus (aMPV) infects respiratory and reproductive tracts of
      domestic poultry, often involving secondary infections, and leads to serious
      economic losses in most parts of the world. While in general disease is
      effectively controlled by live vaccines, reversion to virulence of those vaccines
      has been demonstrated on several occasions. Consensus sequence mutations involved
      in the process have been identified in more than one instance. In one previous
      subtype A aMPV candidate vaccine study, small subpopulations were implicated. In
      the current study, the presence of subpopulations in a subtype B vaccine was
      investigated by deep sequencing. Of the 19 positions where vaccine (strain
      VCO3/50) and progenitor (strain VCO3/60616) consensus sequences differed,
      subpopulations were found to have sequence matching progenitor sequence in 4
      positions. However none of these mutations occurred in a virulent revertant of
      that vaccine, thereby demonstrating that the majority progenitor virus population
      had not survived the attenuation process, hence was not obviously involved in any
      return to virulence. However within the vaccine, a single nucleotide variation
      was found which agreed with consensus sequence of a derived virulent revertant
      virus, hence this and other undetected, potentially virulent subpopulations, can
      be involved in reversion. Much deeper sequencing of progenitor, vaccine and
      revertant may clarify whether problematic virulent subpopulations are present and
      therefore whether these need to be routinely removed during aMPV vaccine
      preparation prior to registration and release. 

PMID- 25865473
TI  - Advances and challenges in mucosal adjuvant technology.
AB  - Adjuvants play attractive roles in enhancement of immune response during
      vaccination; however, due to several challenges, only a limited number of
      adjuvants are licensed by health authorities. The lack of an effective mucosal
      adjuvant is even more significant as none of the licensed adjuvants revealed a
      strong enhancement in immune system after mucosal administration. Over the past
      two decades, several mucosal adjuvants have been developed to deliver antigens to
      the target cells in the mucosal immune system and increase specific immune
      responses. However, the safety and efficacy of these adjuvants for testing in
      human trials is still an important issue, requiring further study. In this
      article, we briefly review the challenges associated with most common mucosal
      adjuvants and discuss potential strategies for targeting the mucosal immune
      system. 

PMID- 25865472
TI  - Single-dose live-attenuated vesicular stomatitis virus-based vaccine protects
      African green monkeys from Nipah virus disease.
AB  - Nipah virus is a zoonotic paramyxovirus that causes severe respiratory and/or
      encephalitic disease in humans, often resulting in death. It is transmitted from
      pteropus fruit bats, which serve as the natural reservoir of the virus, and
      outbreaks occur on an almost annual basis in Bangladesh or India. Outbreaks are
      small and sporadic, and several cases of human-to-human transmission have been
      documented as an important feature of the epidemiology of Nipah virus disease.
      There are no approved countermeasures to combat infection and medical
      intervention is supportive. We recently generated a recombinant replication
      competent vesicular stomatitis virus-based vaccine that encodes a Nipah virus
      glycoprotein as an antigen and is highly efficacious in the hamster model of
      Nipah virus disease. Herein, we show that this vaccine protects African green
      monkeys, a well-characterized model of Nipah virus disease, from disease one
      month after a single intramuscular administration of the vaccine. Vaccination
      resulted in a rapid and strong virus-specific immune response which inhibited
      virus shedding and replication. This vaccine platform provides a rapid means to
      afford protection from Nipah virus in an outbreak situation.

PMID- 25865474
TI  - Mineralization dynamics in soil fertilized with seaweed-fish waste compost.
AB  - BACKGROUND: Seaweed and fish waste can be composted together to obtain fertilizer
      with high organic matter and nutrient contents. The nutrients, however, are
      mostly in organic form and must be mineralized to make them available to plants.
      The objective of this work was to establish a usage guideline for the compost by
      studying its mineralization dynamics. Also, the release of inorganic N and C from
      soil fertilized with the compost was monitored and modelled. RESULTS: C and N
      were released throughout the assay, to an extent significantly dependent on
      fertilizer rate. Mineralization of both elements fitted a first-order exponential
      model, and each fertilizer rate required using a specific fitting model. An
      increased rate favoured mineralization (especially of carbon). After 90 days,
      2.3% of C and 7.7% of N were mineralized (and 23.3% of total nitrogen made plant
      available) with the higher rate. CONCLUSION: C mineralization was slow because
      organic matter in the compost was very stable. On the other hand, the relatively
      high initial content in mineral N of the compost increased gradually by the
      effect of mineralization. The amount of N available would suffice to meet the
      requirements of moderately demanding crops at the lower fertilizer rate, and even
      those of more demanding crops at the higher rate.

PMID- 25865475
TI  - Effect of Protocolized Sedation on Clinical Outcomes in Mechanically Ventilated
      Intensive Care Unit Patients: A Systematic Review and Meta-analysis of Randomized
      Controlled Trials.
AB  - OBJECTIVE: To assess the effects of protocolized sedation (algorithm or daily
      interruption) compared with usual care without protocolized sedation on clinical
      outcomes in mechanically ventilated adult intensive care unit (ICU) patients via
      a systematic review and meta-analysis of randomized controlled trials (RCTs).
      METHODS: We searched Ovid MEDLINE, EMBASE, Cochrane CENTRAL, Web of Science, and
      ClinicalTrials.gov from their inception to February 28, 2013. A random-effects
      model was used to synthesize risk ratios (RRs) and weighted mean differences
      (WMDs). RESULTS: Of 4782 records screened, 6 RCTs including 1243 patients met the
      inclusion criteria. Protocolized sedation was associated with significant
      reductions in overall mortality (RR, 0.85; 95% CI, 0.74 to 0.97; P=.02; number
      needed to treat, 20; P=.11), ICU length of stay (WMD, -1.73 days; 95% CI, -3.32
      to -0.14 days; P=.03), hospital length of stay (WMD, -3.55 days; 95% CI, -5.98 to
      -1.12 days; P=.004), and tracheostomy (RR, 0.69; 95% CI, 0.50 to 0.96; P=.03;
      number needed to treat, 16.6; P=.04; 5 RCTs) compared with usual care.
      Protocolized sedation produced no significant differences in duration of
      mechanical ventilation (WMD, -1.04 days; 95% CI, -2.54 to 0.47 days; P=.18),
      reintubation (RR, 0.78; 95% CI, 0.52 to 1.15; P=.21; 3 RCTs), and self-extubation
      (RR, 1.49; 95% CI, 0.46 to 4.82; P=.51; 4 RCTs) compared with usual care.
      Included studies did not report delirium incidence. CONCLUSION: In mechanically
      ventilated adults in closed, nonspecialty ICUs, protocolized sedation seems to
      decrease overall mortality (15%), ICU and hospital lengths of stay (1.73 and 3.55
      days, respectively), and tracheostomy (31%) compared with usual care without
      protocolized sedation.

PMID- 25865476
TI  - Refining the ammonia hypothesis: a physiology-driven approach to the treatment of
      hepatic encephalopathy.
AB  - Hepatic encephalopathy (HE) is one of the most important complications of
      cirrhosis and portal hypertension. Although the etiology is incompletely
      understood, it has been linked to ammonia directly and indirectly. Our goal is to
      review for the clinician the mechanisms behind hyperammonemia and the
      pathogenesis of HE to explain the rationale for its therapy. We reviewed articles
      collected through a search of MEDLINE/PubMed, Cochrane Database of Systematic
      Reviews, and Google Scholar between October 1, 1948, and December 8, 2014, and by
      a manual search of citations within retrieved articles. Search terms included
      hepatic encephalopathy, ammonia hypothesis, brain and ammonia, liver failure and
      ammonia, acute-on-chronic liver failure and ammonia, cirrhosis and ammonia,
      portosytemic shunt, ammonia and lactulose, rifaximin, zinc, and nutrition.
      Ammonia homeostatsis is a multiorgan process involving the liver, brain, kidneys,
      and muscle as well as the gastrointestinal tract. Indeed, hyperammonemia may be
      the first clue to poor functional reserves, malnutrition, and impending
      multiorgan dysfunction. Furthermore, the neuropathology of ammonia is critically
      linked to states of systemic inflammation and endotoxemia. Given the complex
      interplay among ammonia, inflammation, and other factors, ammonia levels have
      questionable utility in the staging of HE. The use of nonabsorbable
      disaccharides, antibiotics, and probiotics reduces gut ammoniagenesis and, in the
      case of antibiotics and probiotics, systemic inflammation. Nutritional support
      preserves urea cycle function and prevents wasting of skeletal muscle, a
      significant site of ammonia metabolism. Correction of hypokalemia, hypovolemia,
      and acidosis further assists in the reduction of ammonia production in the
      kidney. Finally, early and aggressive treatment of infection, avoidance of
      sedatives, and modification of portosystemic shunts are also helpful in reducing
      the neurocognitive effects of hyperammonemia. Refining the ammonia hypothesis to
      account for these other factors instructs a solid foundation for the effective
      treatment and prevention of hepatic encephalopathy. 

PMID- 25865477
TI  - Radiochromic film-based quality assurance for CT-based high-dose-rate
      brachytherapy.
AB  - PURPOSE: In the past, film dosimetry was developed into a powerful tool for
      external beam radiotherapy treatment verification and quality assurance. The
      objective of this work was the development and clinical testing of the EBT3 model
      GafChromic film based brachytherapy quality assurance (QA) system. METHODS AND
      MATERIALS: Retrospective dosimetry study was performed to test a patient-specific
      QA system for preoperative endorectal brachytherapy that uses a radiochromic film
      dosimetry system. A dedicated phantom for brachytherapy applicator used for
      rectal cancer treatment was fabricated enabling us to compare calculated-to
      measured dose distributions. Starting from the same criteria used for external
      beam intensity-modulated radiation therapy QA (3%, 3 mm), passing criteria for
      high- and low-dose gradient regions were subsequently determined. Finally, we
      investigated the QA system's sensitivity to controlled source positional errors
      on selected patient plans. RESULTS: In low-dose gradient regions, measured dose
      distributions with criteria of 3%, 3 mm barely passed the test, as they showed
      95% passing pixels. However, in the high-dose gradient region, a more stringent
      condition could be established. Both criteria of 2%, 3 mm and 3%, 2 mm with gamma
      function calculated using normalization to the same absolute dose value in both
      measured and calculated dose distributions, and matrix sizes rescaled to match
      each other showed more than 95% of pixels passing, on average, for 15 patient
      plans analyzed. CONCLUSIONS: Although the necessity of the patient-specific
      brachytherapy QA needs yet to be justified, we described a radiochromic film
      dosimetry-based QA system that can be a part of the brachytherapy commissioning
      process, as well as yearly QA program.

PMID- 25865478
TI  - It is a great pleasure to introduce to you the fourth edition of this year.

PMID- 25865479
TI  - Computer-based measurements of joint space analysis using metacarpal morphometry
      in hand radiograph for evaluation of rheumatoid arthritis.
AB  - AIM AND OBJECTIVES: The aim and objectives are as follows: (i) to perform an
      automated segmentation of the hand from radiographs using a dual tree complex
      wavelet-based watershed algorithm; ii) to compare the measured statistical
      features of the joint space of the hand using gray level co-occurrence matrix
      (GLCM) method with standard diagnostic parameters of rheumatoid arthritis (RA).
      METHODS: Fifty-three patients with RA and 17 age- and sex-matched healthy
      controls were included in the study. The erythrocyte sedimentation rate (ESR), C
      reactive protein, rheumatoid factor, health assessment questionnaire score (HAQ),
      disease activity score (DAS) and hand radiographs of all the subjects were
      obtained. Joint space width and cortical thickness were measured in
      metacarpophalangeal joints (MCP) and metacarpal bone semi-automatically using
      MIMICS software. Dual tree complex wavelet transform-based watershed algorithm
      was applied for automated segmentation, and feature extraction was performed
      using the GLCM method in hand radiographs of the total population. RESULTS: In
      the RA group (n = 53), the joint space width measured in the MCP1, MCP3, MCP5 of
      the hand were reduced significantly (P < 0.01) by 16.4%, 15.6%, and 17.5%,
      respectively compared to the normal group (n = 17). The measured combined
      cortical thickness at the second, third and fourth metacarpal bones of the hand
      were reduced significantly (P < 0.01) by 9.5%, 12% and 8%, respectively in the RA
      group compared to the normal group. CONCLUSION: The dual tree complex wavelet
      transform-based watershed algorithm provided effective segmentation in the
      digitized hand radiographs. The standard diagnostic parameters for RA were highly
      correlated with measured statistical features at MCP3 hand joint in the total
      population studied.

PMID- 25865480
TI  - Implementing routine outcome measurement in psychiatric rehabilitation services
      in Israel.
AB  - In this article we present the design, development and implementation of the
      Psychiatric Rehabilitation Routine Outcome Measurement (PR-ROM) project, the
      first systematic effort to implement mental health routine outcome measures in
      Israel. The goal of the PR-ROM is to provide updated information about the
      process and impact of psychiatric rehabilitation services in Israel and to
      establish a sustainable infrastructure and foundation for routine outcome
      monitoring of rehabilitation services to improve care, inform policy, generate
      incentives for service improvement, increase informed decision-making and provide
      data for research purposes. The rehabilitation services evaluated and the
      characteristics of the population being served are described and the methods and
      nature of the collected data as well as some preliminary findings are presented.
      We discuss the major barriers encountered, our efforts to deal with them and
      lessons learned during the process. We conclude with a description of the current
      state of the initiative and plans for the future. 

PMID- 25865481
TI  - Substrates Control Multimerization and Activation of the Multi-Domain ATPase
      Motor of Type VII Secretion.
AB  - Mycobacterium tuberculosis and Staphylococcus aureus secrete virulence factors
      via type VII protein secretion (T7S), a system that intriguingly requires all of
      its secretion substrates for activity. To gain insights into T7S function, we
      used structural approaches to guide studies of the putative translocase EccC, a
      unique enzyme with three ATPase domains, and its secretion substrate EsxB. The
      crystal structure of EccC revealed that the ATPase domains are joined by
      linker/pocket interactions that modulate its enzymatic activity. EsxB binds via
      its signal sequence to an empty pocket on the C-terminal ATPase domain, which is
      accompanied by an increase in ATPase activity. Surprisingly, substrate binding
      does not activate EccC allosterically but, rather, by stimulating its
      multimerization. Thus, the EsxB substrate is also an integral T7S component,
      illuminating a mechanism that helps to explain interdependence of substrates, and
      suggests a model in which binding of substrates modulates their coordinate
      release from the bacterium. 

PMID- 25865482
TI  - Bending gradients: how the intestinal stem cell gets its home.
AB  - We address the mechanism by which adult intestinal stem cells (ISCs) become
      localized to the base of each villus during embryonic development. We find that,
      early in gut development, proliferating progenitors expressing ISC markers are
      evenly distributed throughout the epithelium, in both the chick and mouse.
      However, as the villi form, the putative stem cells become restricted to the base
      of the villi. This shift in the localization is driven by mechanically influenced
      reciprocal signaling between the epithelium and underlying mesenchyme. Buckling
      forces physically distort the shape of the morphogenic field, causing local
      maxima of epithelial signals, in particular Shh, at the tip of each villus. This
      induces a suite of high-threshold response genes in the underlying mesenchyme to
      form a signaling center called the "villus cluster." Villus cluster signals,
      notably Bmp4, feed back on the overlying epithelium to ultimately restrict the
      stem cells to the base of each villus.

PMID- 25865485
TI  - Motor neuron disease-frontotemporal dementia: a clinical continuum.
AB  - Overlap between motor neuron disease (MND) and frontotemporal dementia (FTD)
      occurs at clinical, genetic and pathological levels, and has been recently
      strengthened through the discovery of the C9orf72 genetic expansion. MND is now
      considered to be a multisystem disorder in which cognitive involvement may be
      present and, in some cases, may evolve to frank FTD. Identifying cognitive
      features in MND can be challenging, while, similarly, motor dysfunction in FTD
      may be overlooked. As such, the present review aims to decipher the variety of
      overlapping clinical features across the MND-FTD continuum. 

PMID- 25865484
TI  - The role of the kynurenine pathway in suicidality in adolescent major depressive
      disorder.
AB  - The neuroimmunological kynurenine pathway (KP) has been implicated in major
      depressive disorder (MDD) in adults and adolescents, most recently in suicidality
      in adults. The KP is initiated by the enzyme indoleamine 2,3-dioxygenase (IDO),
      which degrades tryptophan (TRP) into kynurenine (KYN) en route to neurotoxins.
      Here, we examined the KP in 20 suicidal depressed adolescents-composed of past
      attempters and those who expressed active suicidal intent-30 non-suicidal
      depressed youth, and 22 healthy controls (HC). Plasma levels of TRP, KYN, 3
      hydroxyanthranilic acid (3-HAA), and KYN/TRP (index of IDO) were assessed.
      Suicidal adolescents showed decreased TRP and elevated KYN/TRP compared to both
      non-suicidal depressed adolescents and HC. Findings became more significantly
      pronounced when excluding medicated participants, wherein there was also a
      significant positive correlation between KYN/TRP and suicidality. Finally,
      although depressed adolescents with a history of suicide attempt differed from
      acutely suicidal adolescents with respect to disease severity, anhedonia, and
      suicidality, the groups did not differ in KP measures. Our findings suggest a
      possible specific role of the KP in suicidality in depressed adolescents, while
      illustrating the clinical phenomenon that depressed adolescents with a history of
      suicide attempt are similar to acutely suicidal youth and are at increased risk
      for completion of suicide. 

PMID- 25865483
TI  - Maturation and Diversity of the VRC01-Antibody Lineage over 15 Years of Chronic
      HIV-1 Infection.
AB  - HIV-1-neutralizing antibodies develop in most HIV-1-infected individuals,
      although highly effective antibodies are generally observed only after years of
      chronic infection. Here, we characterize the rate of maturation and extent of
      diversity for the lineage that produced the broadly neutralizing antibody VRC01
      through longitudinal sampling of peripheral B cell transcripts over 15 years and
      co-crystal structures of lineage members. Next-generation sequencing identified
      VRC01-lineage transcripts, which encompassed diverse antibodies organized into
      distinct phylogenetic clades. Prevalent clades maintained characteristic features
      of antigen recognition, though each evolved binding loops and disulfides that
      formed distinct recognition surfaces. Over the course of the study period, VRC01
      lineage clades showed continuous evolution, with rates of ~2 substitutions per
      100 nucleotides per year, comparable to that of HIV-1 evolution. This high rate
      of antibody evolution provides a mechanism by which antibody lineages can achieve
      extraordinary diversity and, over years of chronic infection, develop effective
      HIV-1 neutralization.

PMID- 25865486
TI  - Scaffold-fused riboregulators for enhanced gene activation in Synechocystis sp.
      PCC 6803.
AB  - Cyanobacteria are an attractive host for biofuel production because they can
      produce valuable chemical compounds from CO2 fixed by photosynthesis. However,
      the available genetic tools that enable precise gene regulation for the
      applications of synthetic biology are insufficient. Previously, we engineered an
      RNA-based posttranscriptional regulator, termed riboregulator, for the control of
      target gene expression in cyanobacterium Synechocystis sp. PCC 6803. Moreover, we
      enhanced the gene regulation ability of the riboregulators in Escherichia coli by
      fusing and engineering a scaffold sequence derived from naturally occurring E.
      coli noncoding small RNAs. Here, we demonstrated that the scaffold sequence fused
      to the riboregulators improved their gene regulation ability in Synechocystis sp.
      PCC 6803. To further improve gene regulation, we expressed an exogenous RNA
      chaperone protein that is responsible for noncoding small RNA-mediated gene
      regulation, which resulted in higher target gene expression. The scaffold
      sequence derived from natural E. coli noncoding small RNAs is effective for
      designing RNA-based genetic tools and scaffold-fused riboregulators are a strong
      RNA-tool to regulate gene expression in cyanobacteria.

PMID- 25865487
TI  - Energy transfer pathways in semiconducting carbon nanotubes revealed using two
      dimensional white-light spectroscopy.
AB  - Thin film networks of highly purified semiconducting carbon nanotubes (CNTs) are
      being explored for energy harvesting and optoelectronic devices because of their
      exceptional transport and optical properties. The nanotubes in these films are in
      close contact, which permits energy to flow through the films, although the
      pathways and mechanisms for energy transfer are largely unknown. Here we use a
      broadband continuum to collect femtosecond two-dimensional white-light spectra.
      The continuum spans 500 to 1,300 nm, resolving energy transfer between all
      combinations of bandgap (S1) and higher (S2) transitions. We observe ultrafast
      energy redistribution on the S2 states, non-Forster energy transfer on the S1
      states and anti-correlated energy levels. The two-dimensional spectra reveal
      competing pathways for energy transfer, with S2 excitons taking routes depending
      on the bandgap separation, whereas S1 excitons relax independent of the bandgap.
      These observations provide a basis for understanding and ultimately controlling
      the photophysics of energy flow in CNT-based devices. 

PMID- 25865488
TI  - Longitudinal associations between physical activity and depression scores in
      Swedish women followed 32 years.
AB  - OBJECTIVE: Physical activity is negatively associated with depressive symptoms.
      However, few studies consider dynamic associations of changes in physical
      activity and reciprocal relationships. This study aimed to perform comprehensive
      evaluations of relationships between physical activity and depression scores in
      women followed from mid- to late life. METHOD: The Prospective Population Study
      of Women in Gothenburg, Sweden, provided repeated measures of self-reported
      physical activity and depressive symptoms between 1974 and 2005 (baseline N =
      676, 84.5% response rate). Depressive symptoms were assessed using the Montgomery
      Asberg Depression Rating Scale, and physical activity was evaluated by the Saltin
      Grimby Physical Activity Level Scale. Latent growth curve analyses were used to
      evaluate associations of change, and cross-lagged models were used to study the
      reciprocal relationship between physical activity and depression scores. RESULTS:
      At baseline, lower levels of physical activity were related to higher depression
      scores. Individuals with decreasing physical activity over time evidenced higher
      depression scores at 32-year follow-up. Higher average baseline depression score
      was related to declining levels of physical activity at subsequent examinations.
      CONCLUSION: Reduced physical activity may be a long-term consequence of
      depression. It is important to address individual changes in physical activity
      and not merely absolute levels of physical activity in relationship to
      depression.

PMID- 25865489
TI  - Persistence of external signs in Pacific herring Clupea pallasii Valenciennes
      with ichthyophoniasis.
AB  - The progression of external signs of Ichthyophonus infection in Pacific herring
      Clupea pallasii Valenciennes was highly variable and asynchronous after
      intraperitoneal injection with pure parasite preparations; however, external
      signs generally persisted through the end of the study (429 days post-exposure).
      Observed signs included papules, erosions and ulcers. The prevalence of external
      signs plateaued 35 days post-exposure and persisted in 73-79% of exposed
      individuals through the end of the first experiment (147 days post-exposure).
      Among a second group of infected herring, external signs completely resolved in
      only 10% of the fish after 429 days. The onset of mortality preceded the
      appearance of external signs. Histological examination of infected skin and
      skeletal muscle tissues indicated an apparent affinity of the parasite for host
      red muscle. Host responses consisted primarily of granulomatous inflammation,
      fibrosis and necrosis in the skeletal muscle and other tissues. The persistence
      and asynchrony of external signs and host response indicated that they were
      neither a precursor to host mortality nor did they provide reliable metrics for
      hindcasting on the date of exposure. However, the long-term persistence of
      clinical signs in Pacific herring may be useful in ascertaining the population
      level impacts of ichthyophoniasis in regularly observed populations.

PMID- 25865490
TI  - miR-148a dependent apoptosis of bladder cancer cells is mediated in part by the
      epigenetic modifier DNMT1.
AB  - Urothelial cell carcinoma of the bladder (UCCB) is the most common form of
      bladder cancer and it is estimated that ~15,000 people in the United States
      succumbed to this disease in 2013. Bladder cancer treatment options are limited
      and research to understand the molecular mechanisms of this disease is needed to
      design novel therapeutic strategies. Recent studies have shown that microRNAs
      play pivotal roles in the progression of cancer. miR-148a has been shown to serve
      as a tumor suppressor in cancers of the prostate, colon, and liver, but its role
      in bladder cancer has never been elucidated. Here we show that miR-148a is down
      regulated in UCCB cell lines. We demonstrate that overexpression of miR-148a
      leads to reduced cell viability through an increase in apoptosis rather than an
      inhibition of proliferation. We additionally show that miR-148a exerts this
      effect partially by attenuating expression of DNA methyltransferase 1 (DNMT1).
      Finally, our studies demonstrate that treating cells with both miR-148a and
      either cisplatin or doxorubicin is either additive or synergistic in causing
      apoptosis. These data taken together suggest that miR-148a is a tumor suppressor
      in UCCB and could potentially serve as a novel therapeutic for this malignancy.

PMID- 25865491
TI  - Stability of edentulous, atrophic mandibles after insertion of different dental
      implants. A biomechanical study.
AB  - OBJECTIVES: Fractures of the atrophic edentulous mandible are a rare complication
      that can become severe after the insertion of dental implants. This in vitro
      study investigated the effects of different implant settings varying in number,
      diameter, and length. and the influence of a fixed bar. MATERIALS AND METHODS: In
      biomechanical experiments on artificial mandibles, an unmodified reference group,
      four implant settings with two different implants, and the effect of adding a
      fixed bar to these settings were tested. All specimens were loaded with incisal
      biting forces until failure due to fracture. RESULTS: Implants weakened all
      specimens significantly compared with those in the reference group. Without a
      fixed bar, four short and thick implants showed the best results, with high
      significance. With a fixed bar, four long and thin implants withstood the highest
      loads. The addition of fixed bars reduced the differences between the implant
      settings. Fixed bars did not show increased stability for all groups; however,
      these groups showed a higher mean strength. CONCLUSIONS: Four implants with a
      short and thick design should be the first choice when implants are placed
      without a fixed bar in an atrophic mandible. With a fixed bar, four long and thin
      implants should be used.

PMID- 25865492
TI  - Mutations in PYCR2, Encoding Pyrroline-5-Carboxylate Reductase 2, Cause
      Microcephaly and Hypomyelination.
AB  - Despite recent advances in understanding the genetic bases of microcephaly, a
      large number of cases of microcephaly remain unexplained, suggesting that many
      microcephaly syndromes and associated genes have yet to be identified. Here, we
      report mutations in PYCR2, which encodes an enzyme in the proline biosynthesis
      pathway, as the cause of a unique syndrome characterized by postnatal
      microcephaly, hypomyelination, and reduced cerebral white-matter volume. Linkage
      mapping and whole-exome sequencing identified homozygous mutations (c.355C>T
      [p.Arg119Cys] and c.751C>T [p.Arg251Cys]) in PYCR2 in the affected individuals of
      two consanguineous families. A lymphoblastoid cell line from one affected
      individual showed a strong reduction in the amount of PYCR2. When mutant cDNAs
      were transfected into HEK293FT cells, both variant proteins retained normal
      mitochondrial localization but had lower amounts than the wild-type protein,
      suggesting that the variant proteins were less stable. A PYCR2-deficient HEK293FT
      cell line generated by genome editing with the clustered regularly interspaced
      short palindromic repeat (CRISPR)-Cas9 system showed that PYCR2 loss of function
      led to decreased mitochondrial membrane potential and increased susceptibility to
      apoptosis under oxidative stress. Morpholino-based knockdown of a zebrafish PYCR2
      ortholog, pycr1b, recapitulated the human microcephaly phenotype, which was
      rescued by wild-type human PYCR2 mRNA, but not by mutant mRNAs, further
      supporting the pathogenicity of the identified variants. Hypomyelination and the
      absence of lax, wrinkly skin distinguishes this condition from that caused by
      previously reported mutations in the gene encoding PYCR2's isozyme, PYCR1,
      suggesting a unique and indispensable role for PYCR2 in the human CNS during
      development.

PMID- 25865493
TI  - Mutations Impairing GSK3-Mediated MAF Phosphorylation Cause Cataract, Deafness,
      Intellectual Disability, Seizures, and a Down Syndrome-like Facies.
AB  - Transcription factors operate in developmental processes to mediate inductive
      events and cell competence, and perturbation of their function or regulation can
      dramatically affect morphogenesis, organogenesis, and growth. We report that a
      narrow spectrum of amino-acid substitutions within the transactivation domain of
      the v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog (MAF), a leucine
      zipper-containing transcription factor of the AP1 superfamily, profoundly affect
      development. Seven different de novo missense mutations involving conserved
      residues of the four GSK3 phosphorylation motifs were identified in eight
      unrelated individuals. The distinctive clinical phenotype, for which we propose
      the eponym Ayme-Gripp syndrome, is not limited to lens and eye defects as
      previously reported for MAF/Maf loss of function but includes sensorineural
      deafness, intellectual disability, seizures, brachycephaly, distinctive flat
      facial appearance, skeletal anomalies, mammary gland hypoplasia, and reduced
      growth. Disease-causing mutations were demonstrated to impair proper MAF
      phosphorylation, ubiquitination and proteasomal degradation, perturbed gene
      expression in primary skin fibroblasts, and induced neurodevelopmental defects in
      an in vivo model. Our findings nosologically and clinically delineate a
      previously poorly understood recognizable multisystem disorder, provide evidence
      for MAF governing a wider range of developmental programs than previously
      appreciated, and describe a novel instance of protein dosage effect severely
      perturbing development.

PMID- 25865494
TI  - Genome-wide Analysis of Body Proportion Classifies Height-Associated Variants by
      Mechanism of Action and Implicates Genes Important for Skeletal Development.
AB  - Human height is a composite measurement, reflecting the sum of leg, spine, and
      head lengths. Many common variants influence total height, but the effects of
      these or other variants on the components of height (body proportion) remain
      largely unknown. We studied sitting height ratio (SHR), the ratio of sitting
      height to total height, to identify such effects in 3,545 African Americans and
      21,590 individuals of European ancestry. We found that SHR is heritable: 26% and
      39% of the total variance of SHR can be explained by common variants in European
      and African Americans, respectively, and global European admixture is negatively
      correlated with SHR in African Americans (r(2) ~ 0.03). Six regions reached
      genome-wide significance (p < 5 * 10(-8)) for association with SHR and overlapped
      biological candidate genes, including TBX2 and IGFBP3. We found that 130 of 670
      height-associated variants are nominally associated (p < 0.05) with SHR, more
      than expected by chance (p = 5 * 10(-40)). At these 130 loci, the height
      increasing alleles are associated with either a decrease (71 loci) or increase
      (59 loci) in SHR, suggesting that different height loci disproportionally affect
      either leg length or spine/head length. Pathway analyses via DEPICT revealed that
      height loci affecting SHR, and especially those affecting leg length, show
      enrichment of different biological pathways (e.g., bone/cartilage/growth plate
      pathways) than do loci with no effect on SHR (e.g., embryonic development). These
      results highlight the value of using a pair of related but orthogonal phenotypes,
      in this case SHR with height, as a prism to dissect the biology underlying
      genetic associations in polygenic traits and diseases.

PMID- 25865495
TI  - Mutations in the GABA Transporter SLC6A1 Cause Epilepsy with Myoclonic-Atonic
      Seizures.
AB  - GAT-1, encoded by SLC6A1, is one of the major gamma-aminobutyric acid (GABA)
      transporters in the brain and is responsible for re-uptake of GABA from the
      synapse. In this study, targeted resequencing of 644 individuals with epileptic
      encephalopathies led to the identification of six SLC6A1 mutations in seven
      individuals, all of whom have epilepsy with myoclonic-atonic seizures (MAE). We
      describe two truncations and four missense alterations, all of which most likely
      lead to loss of function of GAT-1 and thus reduced GABA re-uptake from the
      synapse. These individuals share many of the electrophysiological properties of
      Gat1-deficient mice, including spontaneous spike-wave discharges. Overall,
      pathogenic mutations occurred in 6/160 individuals with MAE, accounting for ~4%
      of unsolved MAE cases.

PMID- 25865497
TI  - The complete chloroplast genome sequence of Anoectochilus roxburghii.
AB  - The complete chloroplast sequence of the Anoectochilus roxburghii, a popular
      traditional Chinese medicine for the treatment of cancer, was determined in this
      study. The chloroplast genome (cpDNA)^ was 152,802 bp in length, containing a
      pair of inverted repeats of 52,728 bp separated by a large single-copy region and
      a small single-copy region of 82,641 bp and 17,433 bp, respectively. The
      chloroplast genome encodes 116 predicted functional genes, including 81 protein
      coding genes, four ribosomal RNA genes, and 31 transfer RNA genes, 25 of which
      are duplicated in the inverted repeat regions. The cpDNA is GC-rich (36.9%).

PMID- 25865498
TI  - Accelerating plant DNA barcode reference library construction using herbarium
      specimens: improved experimental techniques.
AB  - A well-covered reference library is crucial for successful identification of
      species by DNA barcoding. The biggest difficulty in building such a reference
      library is the lack of materials of organisms. Herbarium collections are
      potentially an enormous resource of materials. In this study, we demonstrate that
      it is likely to build such reference libraries using the reconstructed (self
      primed PCR amplified) DNA from the herbarium specimens. We used 179 rosaceous
      specimens to test the effects of DNA reconstruction, 420 randomly sampled
      specimens to estimate the usable percentage and another 223 specimens of true
      cherries (Cerasus, Rosaceae) to test the coverage of usable specimens to the
      species. The barcode rbcLb (the central four-sevenths of rbcL gene) and matK was
      each amplified in two halves and sequenced on Roche GS 454 FLX+. DNA from the
      herbarium specimens was typically shorter than 300 bp. DNA reconstruction enabled
      amplification fragments of 400-500 bp without bringing or inducing any sequence
      errors. About one-third of specimens in the national herbarium of China (PE) were
      proven usable after DNA reconstruction. The specimens in PE cover all Chinese
      true cherry species and 91.5% of vascular species listed in Flora of China. It is
      very possible to build well-covered reference libraries for DNA barcoding of
      vascular species in China. As exemplified in this study, DNA reconstruction and
      DNA-labelled next-generation sequencing can accelerate the construction of local
      reference libraries. By putting the local reference libraries together, a global
      library for DNA barcoding becomes closer to reality.

PMID- 25865499
TI  - Fabry disease in a geriatric population.

PMID- 25865496
TI  - Lupus Risk Variant Increases pSTAT1 Binding and Decreases ETS1 Expression.
AB  - Genetic variants at chromosomal region 11q23.3, near the gene ETS1, have been
      associated with systemic lupus erythematosus (SLE), or lupus, in independent
      cohorts of Asian ancestry. Several recent studies have implicated ETS1 as a
      critical driver of immune cell function and differentiation, and mice deficient
      in ETS1 develop an SLE-like autoimmunity. We performed a fine-mapping study of
      14,551 subjects from multi-ancestral cohorts by starting with genotyped variants
      and imputing to all common variants spanning ETS1. By constructing genetic models
      via frequentist and Bayesian association methods, we identified 16 variants that
      are statistically likely to be causal. We functionally assessed each of these
      variants on the basis of their likelihood of affecting transcription factor
      binding, miRNA binding, or chromatin state. Of the four variants that we
      experimentally examined, only rs6590330 differentially binds lysate from B cells.
      Using mass spectrometry, we found more binding of the transcription factor signal
      transducer and activator of transcription 1 (STAT1) to DNA near the risk allele
      of rs6590330 than near the non-risk allele. Immunoblot analysis and chromatin
      immunoprecipitation of pSTAT1 in B cells heterozygous for rs6590330 confirmed
      that the risk allele increased binding to the active form of STAT1. Analysis with
      expression quantitative trait loci indicated that the risk allele of rs6590330 is
      associated with decreased ETS1 expression in Han Chinese, but not other ancestral
      cohorts. We propose a model in which the risk allele of rs6590330 is associated
      with decreased ETS1 expression and increases SLE risk by enhancing the binding of
      pSTAT1.

PMID- 25865500
TI  - Arabidopsis thaliana HomeoBox 1 (AtHB1), a Homedomain-Leucine Zipper I (HD-Zip I)
      transcription factor, is regulated by PHYTOCHROME-INTERACTING FACTOR 1 to promote
      hypocotyl elongation.
AB  - Arabidopsis thaliana HomeoBox 1 (AtHB1) is a homeodomain-leucine zipper
      transcription factor described as a transcriptional activator with unknown
      function. Its role in A. thaliana development was investigated. AtHB1 expression
      was analyzed in transgenic plants bearing its promoter region fused to reporter
      genes. Knock-down mutant and overexpressor plant phenotypes were analyzed in
      different photoperiod regimes. AtHB1 was mainly expressed in hypocotyls and roots
      and up-regulated in seedlings grown under a short-day photoperiod. AtHB1 knock
      down mutants and overexpressors showed shorter and longer hypocotyls,
      respectively, than wild type (WT). AtHB1 transcript levels were lower in
      PHYTOCHROME-INTERACTING FACTOR 1 (PIF1) mutants than in controls, suggesting that
      AtHB1 is regulated by PIF1 in hypocotyls. beta-glucuronidase (GUS) activity in
      Nicotiana benthamiana leaves cotransformed with PromAtHB1::GUS and 35S::PIF1
      indicated that PIF1 induces AtHB1 expression. Hypocotyl lenght was measured in
      seedlings of athb1, pif1, or double athb1/pif1 mutants and PIF1 or AtHB1
      overexpressors in WT, athb1 or pif1 backgrounds, both in short- or long-day.
      These analyses allowed us to determine that AtHB1 is a factor acting downstream
      of PIF1. Finally, a transcriptome analysis of athb1 mutant hypocotyls revealed
      that AtHB1 regulates genes involved in cell wall composition and elongation. The
      results suggest that AtHB1 acts downstream of PIF1 to promote hypocotyl
      elongation, especially in response to short-day photoperiods. 

PMID- 25865501
TI  - ERRs Mediate a Metabolic Switch Required for Somatic Cell Reprogramming to
      Pluripotency.
AB  - Cell metabolism is adaptive to extrinsic demands; however, the intrinsic
      metabolic demands that drive the induced pluripotent stem cell (iPSC) program
      remain unclear. Although glycolysis increases throughout the reprogramming
      process, we show that the estrogen-related nuclear receptors (ERRalpha and
      ERRgamma) and their partnered co-factors PGC-1alpha and PGC-1beta are transiently
      induced at an early stage, resulting in a burst of oxidative phosphorylation
      (OXPHOS) activity. Upregulation of ERRalpha or ERRgamma is required for the
      OXPHOS burst in both human and mouse cells, respectively, as well as iPSC
      generation itself. Failure to induce this metabolic switch collapses the
      reprogramming process. Furthermore, we identify a rare pool of Sca1(-)/CD34(-)
      sortable cells that is highly enriched in bona fide reprogramming progenitors.
      Transcriptional profiling confirmed that these progenitors are ERRgamma and PGC
      1beta positive and have undergone extensive metabolic reprogramming. These
      studies characterize a previously unrecognized, ERR-dependent metabolic gate
      prior to establishment of induced pluripotency. 

PMID- 25865503
TI  - Sebaceous gland-a major player in skin homoeostasis.

PMID- 25865502
TI  - A SNP-based consensus genetic map for synteny-based trait targeting in faba bean
      (Vicia faba L.).
AB  - Faba bean (Vicia faba L.) is a globally important nitrogen-fixing legume, which
      is widely grown in a diverse range of environments. In this work, we mine and
      validate a set of 845 SNPs from the aligned transcriptomes of two contrasting
      inbred lines. Each V. faba SNP is assigned by BLAST analysis to a single Medicago
      orthologue. This set of syntenically anchored polymorphisms were then validated
      as individual KASP assays, classified according to their informativeness and
      performance on a panel of 37 inbred lines, and the best performing 757 markers
      used to genotype six mapping populations. The six resulting linkage maps were
      merged into a single consensus map on which 687 SNPs were placed on six linkage
      groups, each presumed to correspond to one of the six V. faba chromosomes. This
      sequence-based consensus map was used to explore synteny with the most closely
      related crop species, lentil and the most closely related fully sequenced genome,
      Medicago. Large tracts of uninterrupted colinearity were found between faba bean
      and Medicago, making it relatively straightforward to predict gene content and
      order in mapped genetic interval. As a demonstration of this, we mapped a flower
      colour gene to a 2-cM interval of Vf chromosome 2 which was highly colinear with
      Mt3. The obvious candidate gene from 78 gene models in the collinear Medicago
      chromosome segment was the previously characterized MtWD40-1 gene controlling
      anthocyanin production in Medicago and resequencing of the Vf orthologue showed a
      putative causative deletion of the entire 5' end of the gene. 

PMID- 25865504
TI  - International standards for fetal growth: relevance of advances in ultrasound
      technology.

PMID- 25865505
TI  - Implementing an Innovative Cardiac Assist System in a Nonuniversity Hospital-
      Feasibility, Complications, and First Results.
AB  - To evaluate the feasibility of implementing a cardiac assist system in a
      nonuniversity hospital we analyzed 18 consecutive patients treated with
      venoarterial membrane oxygenation. The system was used electively in 5/18 (27.8%)
      patients during high-risk interventions. Thirteen patients (72.2%) were treated
      in emergency situations. The extracorporal system could be initiated successfully
      in all patients. Periprocedural complications were hemolysis in 3/18 (16.7%),
      disseminated intravascular coagulation in 2/18 (11.1%), cerebral ischemia in 1/18
      (5.6%), and local infection in 2/18 (11.1%) patients. None of these led to a
      discontinuation of the therapy. All electively treated patients were successfully
      weaned from the extracorporeal system. In 9/13 (69.2%) emergency patients the
      system was removed successfully. The 60-day survival rate of the emergency
      patients was 53.8% (7/13). Our experience confirms that an innovative
      extracorporeal circulatory support system can be implemented in a nonuniversity
      hospital at a tolerable risk and a low complication and high procedural success
      rate. 

PMID- 25865506
TI  - HIV prevention in the world of work in sub-Saharan Africa: research and practice.

PMID- 25865507
TI  - Gendered perceptions of HIV risk among young women and men in a high-HIV
      prevalence setting.
AB  - It has become evident that sexual health and HIV-risk behaviours cannot be
      addressed effectively without paying adequate attention to constructions of
      gender and sexuality. While the body of literature examining these themes is
      growing and becoming more nuanced, there is still a significant gap in our
      understanding of the relationship between gendered sexual identities and
      vulnerabilities to disease. In particular, few studies have explored how youths
      themselves perceive this relationship, and how these perceptions may differ among
      males and females. The purpose of this study was to investigate the differing
      'gendered' perceptions of HIV risk among young women and men in a high-HIV
      prevalence community in South Africa. Five focus groups were conducted with
      youths involved with a local school-based HIV-prevention programme in a resource
      deprived, peri-urban community in KwaZulu-Natal Province. The data were recorded,
      transcribed, translated and thematically coded. We used a critical social science
      approach to inform our collaborative analysis. The findings reveal diverse
      understandings of the relationship between gender and HIV risk. The majority of
      the participants felt that females are more vulnerable to HIV as a result of
      gender inequalities; a minority felt that males are more vulnerable because of
      limited perceived control over their sex drive. Others felt that both sexes are
      equally vulnerable because 'the virus doesn't have a friend.' The theme of
      'responsibility for spreading HIV emerged inductively from the data and also
      involved multiple understandings of gendered responsibility. Explicitly engaging
      with youths in targeted discussions on gendered HIV-related vulnerability and
      responsibility can offer an opportunity to challenge stereotypes and gender
      inequities, as well as inform interventions. 

PMID- 25865508
TI  - Employment discrimination and HIV stigma: survey results from civil society
      organisations and people living with HIV in Africa.
AB  - The article presents findings from three surveys of people living with HIV
      (PLHIV) and civil society organisations about the experience of employment
      discrimination and stigma in the workplace. The work seeks to contribute to
      efforts by businesses and other organisations to effectively respond to the HIV
      epidemic within the world of work, and to deepen our understanding of the ways in
      which HIV stigma and employment discrimination persist in the workplace. The
      findings of global and regional surveys indicate the existence of high levels of
      employment discrimination based on HIV status worldwide, including forced
      disclosure of HIV status, exclusion in the workplace, refusals to hire or
      promote, and terminations of people known to be living with HIV. The survey
      findings show that employment discrimination based on HIV status is experienced
      in all African subregions. Country-level surveys conducted in Kenya and Zambia
      indicated that PLHIV face marked barriers to employment, including discrimination
      in hiring, loss of promotions, and termination because of HIV status.
      Additionally, large variances were found in the degree of support versus
      discrimination that employees living with HIV in those two countries received
      following their disclosure. The discussion emphasises the importance of the
      workplace as a site for intervention and behaviour change. To address this, we
      introduce a conceptual framework - the employment continuum - that maps multiple
      points of entry within the workplace to address HIV-related stigma and
      discrimination. Additional recommendations include: actions to ensure equal
      opportunity in hiring for PLHIV; ensuring that HIV testing is voluntary, never
      mandatory, and that disclosure is not necessary for employment; ensuring
      confidentiality of HIV status; communicating and enforcing HIV-related
      antidiscrimination policies; establishing support groups in the workplace;
      providing safe and confidential processes for resolving complaints of employment
      discrimination; and taking affirmative responsibility to verify that any job
      terminations are not the result of mistreatment or bias. 

PMID- 25865509
TI  - 'The epidemic in this country has the face of a woman': Gender and HIV/AIDS in
      South Africa.
AB  - Epidemiological data clearly show that the highest levels of HIV prevalence occur
      in sub-Saharan Africa. Less visible, however, is the complex combination of
      forces that fuel HIV epidemics in this region - these have been dubbed 'the
      lethal cocktail.' It is this 'cocktail' that creates an enabling environment for
      the spread of HIV. The HIV epidemic in the region is increasingly 'feminised' as
      a growing proportion of new infections occurs among and affects women. The
      gendered pattern of distribution of HIV in South Africa reflects a similar
      pattern. The aim of this article is to interrogate the contextual factors
      underlying the differential vulnerabilities of men and women, and the
      implications for HIV prevention, treatment and care. The analysis, based on a
      review of documents and applicable literature, reveals that a perilous mix of
      biomedical, political, economic, and cultural forces shapes the gendered dynamic
      of the HIV epidemic in South Africa. The article identifies a theoretical
      framework to decode the most common components of this mix, namely: lack of
      access to material resources, cultural norms wherein women are subservient to men
      and masculinity is partly defined in terms of multiple sexual partners and
      intergenerational sex, combined with high levels of violence against women. We
      conclude by offering a framework for gendered interventions for HIV prevention,
      treatment and care. 

PMID- 25865510
TI  - Myths, science and stories: working with peer educators to counter HIV/AIDS
      myths.
AB  - The failure to bring about widespread or effective behavioural change in response
      to South Africa's HIV epidemic requires that new forms of health communication be
      explored. This article reports on an action research project in which a group of
      workplace HIV/AIDS peer educators at a South African mining company recorded
      HIV/AIDS myths that they encountered, around which they then developed stories as
      an alternative response to repeating factual, scientific messages, which seem to
      have little effect on target populations. A total of 16 stories were developed
      during the project. Some of the peer educators appeared to be much better at
      using stories within their activities than others. In part, this was a reflection
      of the enthusiasm and abilities of individual peer educators. It was also
      observed that the stories were used to respond to situations that were sometimes
      quite different from the original stimulus for the story. The complex range of
      skills that allows an individual to introduce and effectively use a story in day
      to-day conversation should not be underestimated. The article suggests that
      rather than repeating the project's focus on developing stories tailored to
      specific HIV/AIDS myths, a more effective approach could be to develop stories
      that support core messages for facilitating HIV prevention, testing and
      treatment. 

PMID- 25865511
TI  - Why HIV/AIDS should be treated as exceptional: arguments from sub-Saharan Africa
      and Eastern Europe.
AB  - The idea that HIV and AIDS gets too much attention and funding emerged in 2008
      with a call to end 'AIDS exceptionalism.' This article outlines a short history
      of AIDS exceptionalism - the idea that HIV and AIDS require a response above and
      beyond 'normal' health interventions and is privileged in terms of attention and
      resources when compared with other diseases - and the reasons for the backlash to
      this idea. We argue that in some settings HIV and AIDS must be treated as
      exceptional. These are the hyperendemic countries of southern Africa, where HIV
      epidemics have shown substantial and lasting demographic and social impact, and
      parts of Eastern Europe where the epidemic is augmenting troubling demographic
      changes, such as declines in fertility rates and population growth, and impacting
      society in nuanced ways. Also included are resource-poor settings, mostly in
      Africa, where the combination of the high number of HIV infections and the cost
      of treatment have created issues concerning donor dependency and sustainable
      responses. An HIV epidemic must be seen as a long-wave event, with complex
      challenges to both HIV prevention and treatment responses. The article reviews
      the available data and literature to provide evidence for our arguments. We
      conclude that the perception that AIDS exceptionalism is outdated ignores the
      complexity of different HIV epidemics and obfuscates the challenges to effective
      responses. 

PMID- 25865512
TI  - Patterns of disclosure and antiretroviral treatment adherence in a South African
      mining workplace programme and implications for HIV prevention.
AB  - Social and psychological barriers to the disclosure of one's seropositive HIV
      status to significant others and poor adherence to taking medications pose
      significant challenges to the scaling-up of access to antiretroviral treatment
      (ART) in the workplace. Such barriers are predictive of sub-optimal treatment
      outcomes and bedevil HIV-prevention interventions at a societal level. Against
      this background, this article explores the lived experiences of 19 HIV-positive
      male participants, between the ages of 33 and 57 years, who were enrolled in an
      ART programme managed at an occupational health clinic at a mining company in
      South Africa. The majority of these mineworkers had been aware of their HIV
      status for between 5 and 7 years. The study explored psychological and relational
      factors, as aspects of these participants lived experiences, which had a bearing
      on their adherence to their ART regimen and the disclosure choices that they made
      regarding their HIV status. In our sample, those participants who were adherent
      demonstrated higher levels of control and acceptance of their HIV infection and
      were more confident in their ability to manage their treatment, while the group
      who were non-adherent presented with lower levels of adherence motivation and
      self-efficacy, difficulties in maintaining a healthy lifestyle and significant
      challenges in maintaining control over their lives. While most of the men
      favoured disclosing their HIV status to their partners for the sake of treatment
      support, they were less sure about disclosing to family members and non-family
      members, respectively, because of their need to protect these persons and due to
      their fear of being stigmatised. It was evident that treatment adherence choices
      and behaviours were impacted by psychological and relational factors, including
      disclosure decisions. We conclude with a bivariate model for understanding the
      adherence behaviours that influenced different patterns of ART adherence among
      the sample, and offer recommendations for HIV-prevention and treatment
      interventions in a mining workplace. 

PMID- 25865513
TI  - Risk management in HIV/AIDS: ethical and economic issues associated with
      restricting HAART access only to adherent patients.
AB  - Like many other developing nations, South Africa faces the challenge of
      mobilising resources in response to the HIV pandemic. There is a large budget gap
      between the ideal and the actual amount of funding needed to achieve universal
      access to highly active antiretroviral therapy (HAART). In addition to financial
      demands, new burdens are being placed on HAART programmes with the emergence of
      HIV drug resistance (HIVDR). Thus, a major threat to successful HAART rollout is
      HIVDR due to non-adherence to HAART. The use of HAART as a primary and secondary
      HIV-prevention strategy could be ineffective in situations characterised by high
      rates of non-adherence. In this context, the research looked at issues related to
      adherence and non-adherence to HAART from the perspective of the provider. Using
      the software TreeAge Pro 2009, we developed a Markov model to project economic
      outcomes for a hypothetical cohort of HIV/AIDS patients on HAART. The model
      compared two scenarios: adherence and non-adherence to HAART. Input data for the
      model was obtained from existing literature on HAART uptake in South Africa.
      Moral arguments were analysed and managed through moral reasoning and critical
      thinking. Discounted lifetime costs for adherent and non-adherent HAART patients
      in South Africa were estimated at US$9 771 and US$14 762, respectively. The model
      showed the loss of 4.55 quality-adjusted life years (QALYs) for non-adherent
      patients, which could be otherwise gained through improved adherence. The
      incremental cost-effectiveness ratio (ICER) indicated that restricting HAART
      access only to adherent patients was the dominant strategy. We suggest that,
      although not a panacea, the withholding or withdrawal of treatment from non
      adherent individuals as a precautionary intervention has economic and moral
      merit. 

PMID- 25865514
TI  - South African HIV/AIDS programming overlooks migration, urban livelihoods, and
      informal workplaces.
AB  - South Africa has the largest population of people living with HIV globally and is
      associated with high population mobility. The majority of migrants move in search
      of improved livelihood opportunities, and many who migrate (both internally and
      across borders) move into urban areas, often through peripheral informal
      settlements where HIV prevalence is shown to be double that of urban formal
      areas. While the relationship between migration and the spread of HIV is
      acknowledged as complex, the context of migration may place individuals at
      increased risk for acquiring HIV. Studies have demonstrated the long-wave impact
      of HIV and AIDS on livelihood activities and, more recently, on patterns of
      migration. Many migrants engage in livelihood strategies situated within the
      urban 'informal economy'; these informal workplaces are often overlooked in
      global and national legislation governing workplace responses to health and HIV
      and AIDS. This study draws on existing research and limited primary data to
      explore the implications of HIV/AIDS programming for diverse migrant groups
      labouring in informal workplaces in Johannesburg, South Africa. We describe three
      case studies: waste-pickers at a dumpsite in a peripheral urban informal
      settlement; barmen and cleaners working in inner-city hotels where sex is also
      sold; and, migrants engaged in informal livelihood activities who are also
      members of burial societies. Given the importance of varied informal livelihood
      activities for diverse migrant groups, particularly in urban areas of South
      Africa, we propose that the national HIV/AIDS response can and should engage with
      internal and cross-border migrants in informal workplaces - which is in line with
      the principle of universal access and will strengthen the national response.
      Especially, we point out the potential for burial societies to provide an entry
      point for HIV/AIDS programming that targets migrant groups involved in the
      informal economy of South African cities. 

PMID- 25865515
TI  - Health literacy as the missing link in the provision of immigrant health care: A
      qualitative study of Southeast Asian immigrant women in Taiwan.
AB  - OBJECTIVES: Language and communication barrier are main contributors to poor
      health outcomes and improper use of health care among immigrants. The purpose of
      this study was to explore and understand specific language and communication
      problems experiences by Southeast Asian immigrant women in Taiwan. DESIGN: This
      qualitative study used focus groups and in-depth interviews to uncover the
      experiences of immigrant women regarding their access to and utilization of
      health care in Taiwan. PARTICIPANTS: Eight focus groups were conducted with 62
      Southeast Asian immigrant women and 23 individual in-depth interviews with a wide
      range of stakeholders who had diverse background and intimate knowledge of
      immigrant-relating health care issues were performed. RESULTS: Directed content
      analysis was applied and identified four major themes concerning conditions that
      influenced immigrant women's use of health information and services: (1) gaining
      access to health information, (2) navigating in health care delivery system, (3)
      interactions during health care encounters, and (4) capability of using health
      information and services. Findings from this study suggest that, without basic
      language and literate skills, the majority of immigrant women had inadequate
      health literacy to manage health information and navigate the Taiwan health care
      system. Interpersonal communication gap between immigrant women and health care
      providers exists because of lack of health literacy in addition al language and
      cultural barriers. CONCLUSION: With limited language and health literacy skills,
      immigrant women face numerous challenges in navigating the health care system,
      interacting with health care providers, and gaining access to proper health care.
      Future efforts are necessary to enhance individual's health literacy and
      establish health literate environment.

PMID- 25865516
TI  - Efficiency of respiratory rate measurements: Comment on Black et al., 2015: "Can
      simple mobile phone applications provide reliable counts of respiratory rates in
      sick infants and children? An initial evaluation of three new applications".

PMID- 25865517
TI  - Limited English proficient Hmong- and Spanish-speaking patients' perceptions of
      the quality of interpreter services.
AB  - BACKGROUND: Language barriers are a large and growing problem for patients in the
      US and around the world. Interpreter services are a standard solution for
      addressing language barriers and most research has focused on utilization of
      interpreter services and their effect on health outcomes for patients who do not
      speak the same language as their healthcare providers including nurses. However,
      there is limited research on patients' perceptions of these interpreter services.
      OBJECTIVE: To examine Hmong- and Spanish-speaking patients' perceptions of
      interpreter service quality in the context of receiving cancer preventive
      services. METHODS: Twenty limited English proficient Hmong (n=10) and Spanish
      speaking participants (n=10) ranging in age from 33 to 75 years were interviewed
      by two bilingual researchers in a Midwestern state. Interviews were audio taped,
      transcribed verbatim, and translated into English. Analysis was done using
      conventional content analysis. RESULTS: The two groups shared perceptions about
      the quality of interpreter services as variable along three dimensions.
      Specifically, both groups evaluated quality of interpreters based on the
      interpreters' ability to provide: (a) literal interpretation, (b) cultural
      interpretation, and (c) emotional interpretation during the health care
      encounter. The groups differed, however, on how they described the consequences
      of poor interpretation quality. Hmong participants described how poor quality
      interpretation could lead to: (a) poor interpersonal relationships among
      patients, providers, and interpreters, (b) inability of patients to follow
      through with treatment plans, and (c) emotional distress for patients.
      CONCLUSIONS: Our study highlights the fact that patients are discerning consumers
      of interpreter services; and could be effective partners in efforts to reform and
      enhance interpreter services.

PMID- 25865518
TI  - Adult encephalitis surveillance: experiences from an Australian prospective
      sentinel site study.
AB  - Few countries routinely collect comprehensive encephalitis data, yet
      understanding the epidemiology of this condition has value for clinical
      management, detecting novel and emerging pathogens, and guiding timely public
      health interventions. When this study was conducted there was no standardized
      diagnostic algorithm to aid identification of encephalitis or systematic
      surveillance for adult encephalitis. In July 2012 we tested three pragmatic
      surveillance options aimed at identifying possible adult encephalitis cases
      admitted to a major Australian hospital: hospital admissions searches, clinician
      notifications and laboratory test alerts (CSF herpes simplex virus requests).
      Eligible cases underwent structured laboratory investigation and a specialist
      panel arbitrated on the final diagnosis. One hundred and thirteen patients were
      initially recruited into the 10-month study; 20/113 (18%) met the study case
      definition, seven were diagnosed with infectious or immune-mediated encephalitis
      and the remainder were assigned alternative diagnoses. The laboratory alert
      identified 90% (102/113) of recruited cases including six of the seven cases of
      confirmed encephalitis suggesting that this may be a practical data source for
      case ascertainment. The application of a standardized diagnostic algorithm and
      specialist review by an expert clinical panel aided diagnosis of patients with
      encephalitis. 

PMID- 25865519
TI  - Surviving workplace adversity: a qualitative study of nurses and midwives and
      their strategies to increase personal resilience.
AB  - AIM: To explore the experiences of Australian nurses and midwives who perceived
      themselves as resilient. The focus of this paper is to report the strategies used
      by a group of nurses and midwives to develop and maintain their resilience,
      despite encountering serious workplace adversity. BACKGROUND: Despite the
      potentially adverse effects of nursing work, many nurses and midwives thrive
      through exercising self-efficacy and coping skills. The relationship between
      thriving and resilience is clear, as resilience refers to the ability to cope
      well with adversity and change. METHODS: The participants were part of an
      instrumental, collective case study investigation of personal resilience amongst
      nurses and midwives. Prior to an innovative, work-based intervention including
      workshops and mentoring, participants were interviewed to collect baseline
      perceptions and experiences of personal resilience and workplace adversity.
      Interview transcripts were analysed thematically. RESULTS: Participants
      attributed their ability to thrive in the workplace to three major influences:
      support networks, personal characteristics and ability to organise work for
      personal resilience. CONCLUSIONS: Participant insights contributed to a deeper
      understanding of personal resilience and highlight future initiatives to enhance
      the ability of nurses and midwives to thrive within health organisations and
      systems. IMPLICATIONS FOR NURSING MANAGEMENT: It is vital that resilience
      enhancing initiatives, such as peer mentoring and tailored work options to
      increase autonomy, are implemented at earlier career phases.

PMID- 25865520
TI  - Evaluating the subject-performed task effect in healthy older adults:
      relationship with neuropsychological tests.
AB  - BACKGROUND: An enhancement in recall of simple instructions is found when actions
      are performed in comparison to when they are verbally presented - the subject
      performed task (SPT) effect. This enhancement has also been found with older
      adults. However, the reason why older adults, known to present a deficit in
      episodic memory, have a better performance for this type of information remains
      unclear. In this article, we explored this effect by comparing the performance on
      the SPT task with the performance on other tasks, in order to understand the
      underlying mechanisms that may explain this effect. OBJECTIVE: We hypothesized
      that both young and older adult groups should show higher recall in SPT compared
      with the verbal learning condition, and that the differences between age groups
      should be lower in the SPT condition. We aimed to explore the correlations
      between these tasks and known neuropsychological tests, and we also measured
      source memory for the encoding condition. DESIGN: A mixed design was used with 30
      healthy older adults, comparing their performance with 30 healthy younger adults.
      Each participant was asked to perform 16 simple instructions (SPT condition) and
      to only read the other 16 instructions (Verbal condition - VT). The test phase
      included a free recall task. Participants were also tested with a set of
      neuropsychological measures (speed of processing, working memory and verbal
      episodic memory). RESULTS: The SPT effect was found for both age groups; but even
      for SPT materials, group differences in recall persisted. Source memory was found
      to be preserved for the two groups. Simple correlations suggested differences in
      correlates of SPT performance between the two groups. However, when controlling
      for age, the SPT and VT tasks correlate with each other, and a measure of
      episodic memory correlated moderately with both SPT and VT performance.
      CONCLUSIONS: A strong effect of SPT was observed for all but one, which still
      displayed the expected aging deficit. The correlations and source memory data
      suggest that the SPT and VT are possibly related in respect to their underlying
      processes, and SPT, instead of being an isolated process, is in connection with
      both the episodic memory and executive function processes. Under these
      circumstances, the SPT seems to contribute to an enhancement of the episodic
      memory trace, presumably from the multimodality it provides, without involving a
      separated set of cognitive mechanisms. Future research using more pure measures
      of other cognitive processes that could be related to SPT is necessary.

PMID- 25865521
TI  - Mathematical model of mycobacterium-host interaction describes physiology of
      persistence.
AB  - Despite extensive studies on the interactions between Mycobacterium tuberculosis
      (M.tb) and macrophages, the mechanism by which pathogen evades anti-microbial
      responses and establishes persistence within the host cell remains unknown. In
      this study, we developed a four-dimensional ODE model to describe the dynamics of
      host-pathogen interactions in the early phase of macrophage infection. The aim
      was to characterize the role of host cellular regulators such as iron and lipids,
      in addition to the bactericidal effector molecule Nitric Oxide. Conditions for
      existence and stability of the equilibrium point were analysed by examining the
      behaviour of the model through numerical simulations. These computational
      investigations revealed that it was the ability of pathogen to interfere with
      iron and lipid homeostatic pathways of the host cell, which ensured a shift in
      balance towards pathogen survival and persistence. Interestingly, small
      perturbations in this equilibrium triggered the cell's bactericidal response,
      thereby producing an oscillatory dynamic for disease progression.

PMID- 25865522
TI  - Analysis of the multi-copied genes and the impact of the redundant protein coding
      sequences on gene annotation in prokaryotic genomes.
AB  - The important roles of duplicated genes in evolutional process have been
      recognized in bacteria, archaebacteria and eukaryotes, while there is very little
      study on the multi-copied protein coding genes that share sequence identity of
      100%. In this paper, the multi-copied protein coding genes in a number of
      prokaryotic genomes are comprehensively analyzed firstly. The results show that 0
      15.93% of the protein coding genes in each genome are multi-copied genes and 0
      16.49% of the protein coding genes in each genome are highly similar with the
      sequence identity >= 80%. Function and COG (Clusters of Orthologous Groups of
      proteins) analysis shows that 64.64% of multi-copied genes concentrate on the
      function of transposase and 86.28% of the COG assigned multi-copied genes
      concentrate on the COG code of 'L'. Furthermore, the impact of redundant protein
      coding sequences on the gene prediction results is studied. The results show that
      the problem of protein coding sequence redundancies cannot be ignored and the
      consistency of the gene annotation results before and after excluding the
      redundant sequences is negatively related with the sequences redundancy degree of
      the protein coding sequences in the training set.

PMID- 25865523
TI  - Molecular characterization of the puroindoline-a and b alleles in synthetic
      hexaploid wheats and in silico functional and structural insights into Pina-D1.
AB  - Kernel hardness determined by two tightly linked Puroindoline genes, Pina-D1 and
      Pinb-D1, located on chromosome 5DS define commercially important characteristics,
      uses, major grades and export markets of wheat. This study was conducted to
      characterize Pina-D1 and Pinb-D1 alleles, in fifteen synthetic hexaploid wheats
      (SHWs) and its relation with grain hardness. Additionally, in silico functional
      analyses of puroindoline-a protein was conducted for better understanding of
      their putative importance in grain quality. Six different Pina-D1 alleles were
      identified in the SHWs, of which three i.e. Pina-D1a, Pina-D1c and Pina-D1d were
      already known whereas the other three had new sequence polymorphisms and were
      designated as Pina-D1w, Pina-D1x and Pina-D1y. Three different Pinb-D1 alleles
      were identified which have been reported earlier and no novel sequence
      polymorphism was detected. It was concluded that despite some primary, secondary
      and 3D structure variations, ligand binding sites and disulfide bonds
      discrepancies, the main features of PINA, i.e. the tryptophan-rich domain, the
      cysteine backbone, the signal peptide and basic identity of the proteins were all
      conserved. In silico analysis showed that puroindolines having binding capacity
      with small parts of prolamins causing celiac disease of human, however their
      potential role is not obvious. Conclusively, the new Pina-D1 alleles with modest
      effect on grain hardness, and insight into their functional and structural
      characteristics are important findings and their putative role in celiac disease
      require further studies to validate. 

PMID- 25865524
TI  - VR-BFDT: A variance reduction based binary fuzzy decision tree induction method
      for protein function prediction.
AB  - In protein function prediction (PFP) problem, the goal is to predict function of
      numerous well-sequenced known proteins whose function is not still known
      precisely. PFP is one of the special and complex problems in machine learning
      domain in which a protein (regarded as instance) may have more than one function
      simultaneously. Furthermore, the functions (regarded as classes) are dependent
      and also are organized in a hierarchical structure in the form of a tree or
      directed acyclic graph. One of the common learning methods proposed for solving
      this problem is decision trees in which, by partitioning data into sharp
      boundaries sets, small changes in the attribute values of a new instance may
      cause incorrect change in predicted label of the instance and finally
      misclassification. In this paper, a Variance Reduction based Binary Fuzzy
      Decision Tree (VR-BFDT) algorithm is proposed to predict functions of the
      proteins. This algorithm just fuzzifies the decision boundaries instead of
      converting the numeric attributes into fuzzy linguistic terms. It has the ability
      of assigning multiple functions to each protein simultaneously and preserves the
      hierarchy consistency between functional classes. It uses the label variance
      reduction as splitting criterion to select the best "attribute-value" at each
      node of the decision tree. The experimental results show that the overall
      performance of the proposed algorithm is promising. 

PMID- 25865525
TI  - A new medium containing mupirocin, acetic acid, and norfloxacin for the selective
      cultivation of bifidobacteria.
AB  - Various culture media have been proposed for the isolation and selective
      enumeration of bifidobacteria. Mupirocin is widely used as a selective factor
      along with glacial acetic acid. TOS (transgalactosylated oligosaccharides) medium
      supplemented with mupirocin is recommended by the International Dairy Federation
      for the detection of bifidobacteria in fermented milk products. Mupirocin media
      with acetic acid are also reliable for intestinal samples in which bifidobacteria
      predominate. However, for complex samples containing more diverse microbiota, the
      selectivity of mupirocin media is limited. Resistance to mupirocin has been
      demonstrated by many anaerobic bacteria, especially clostridia. The objective was
      to identify an antibiotic that inhibits the growth of clostridia and allows the
      growth of bifidobacteria, and to use the identified substance to develop a
      selective cultivation medium for bifidobacteria. The susceptibility of
      bifidobacteria and clostridia to 12 antibiotics was tested on agar using the disk
      diffusion method. Only norfloxacin inhibited the growth of clostridia and did not
      affect the growth of bifidobacteria. Using both pure cultures and faecal samples
      from infants, adults, calves, lambs, and piglets, the optimal concentration of
      norfloxacin in solid cultivation media was determined to be 200 mg/L. Our results
      showed that solid medium containing norfloxacin (200 mg/L) in combination with
      mupirocin (100 mg/L) and glacial acetic acid (1 mL/L) is suitable for the
      enumeration and isolation of bifidobacteria from faecal samples of different
      origins. 

PMID- 25865526
TI  - Studies of host-pathogen interactions and immune-related drug development using
      the silkworm: interdisciplinary immunology, microbiology, and pharmacology
      studies.
AB  - Innate immunity acts as a front-line barrier against invading pathogens, and the
      majority of the components are widely conserved among species. Regulation of
      innate immunity is important for overcoming infections and preventing self
      damaging sepsis. Using the silkworm (Bombyx mori) as an animal model, we
      elucidated the activation processes of innate immunity with emphasis on a
      multifunctional insect cytokine called paralytic peptide. Moreover, we
      established an ex vivo system using silkworm larval specimens to quantitatively
      evaluate the immunostimulatory activity of natural compounds. We observed that
      overactivation of innate immunity in silkworms induces tissue damage followed by
      host death, resembling sepsis-induced multi-organ failure in humans. Here, we
      summarize our recent findings and propose the usefulness of the silkworm as an
      animal model for studying immune regulation and for evaluating compounds with the
      potential to regulate innate immunity. 

PMID- 25865527
TI  - Complications of Stevens-Johnson syndrome beyond the eye and skin.
AB  - INTRODUCTION: Ocular and cutaneous disease are common chronic sequelae of Stevens
      Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and have been well
      described in the literature. Long-term complications affecting other organ
      systems have not been so well described. The purpose of this review article is to
      highlight non-ocular and non-cutaneous chronic complications of SJS/TEN. METHODS:
      The PubMed database was searched for the keywords "Stevens-Johnson syndrome" and
      "toxic epidermal necrolysis" through September 1, 2014. Relevant articles were
      then reviewed in full. RESULTS: 138 articles in the English language were found
      that described chronic sequelae of SJS/TEN. Our search revealed six affected
      organ systems other than the eyes and integument, with chronic sequelae from
      SJS/TEN: respiratory, gastrointestinal/hepatic, oral, otorhinolaryngologic,
      gynecologic/genitourinary, and renal. Complications involving these organs
      systems appeared likely to reduce the quality of life for SJS/TEN survivors.
      DISCUSSION: SJS/TEN is a multi-organ disease requiring multidisciplinary care
      from a variety of specialists. Affected patients have complex hospital stays, and
      their quality of life may be severely impacted by multiple long-term
      complications. We believe that preventative care in the acute setting might limit
      the development and progression of many of the sequelae described above.

PMID- 25865528
TI  - Personalized and precision orthodontic therapy.
AB  - OBJECTIVE: To bring together orthodontic stakeholders from academics, industry,
      and private practice for a series of thematically focused workshops to explore
      and develop the transfer of novel approaches into clinical orthodontic practice.
      SETTING AND SAMPLE POPULATION: Twenty-seven invited speakers, eight poster
      presenters, and participants of the Consortium for Orthodontic Advances in
      Science and Technology (COAST) 2014 Innovators' Workshop at the Eaglewood Resort
      and Spa, Itasca, Illinois, September 11-14, 2014. MATERIAL AND METHODS: Five
      themed sessions involving between 4-7 presentations followed by panel discussions
      were organized. The aims of the discussion sessions were to highlight important
      findings and consider the strength of evidence for these, indicate next steps and
      needed research or technological developments to move forward, and to weigh the
      expected benefits from these findings and steps to implement in clinical
      practice. RESULTS: Among important areas for attention identified were need for
      multiscale and multispecies modeling and experimentation for interspecies
      translation of results; large-scale collaborative efforts within the profession
      to address the need for adequate sample sizes for future genetic studies of
      complex traits such as malocclusion; a consortium approach to improve new
      technologies such as intra-oral scanning and 3D imaging by establishing
      standards; and harnessing the growing body of knowledge about bone biology for
      application in orthodontics. CONCLUSIONS: With increased awareness of the
      potential of current and emerging technologies, translation of personalized and
      precision approaches in the field of orthodontics holds ever-increasing promise.

PMID- 25865529
TI  - Saturation of the biological response to orthodontic forces and its effect on the
      rate of tooth movement.
AB  - OBJECTIVES: Investigate the expression and activity of inflammatory markers in
      response to different magnitudes of orthodontic forces and correlate this
      response with other molecular and cellular events during orthodontic tooth
      movement. SETTING AND SAMPLE POPULATION: CTOR Laboratory; 245 Sprague Dawley male
      rats. METHODS AND MATERIALS: Control, sham, and 5 different experimental groups
      received different magnitudes of force on the right maxillary first molar using a
      coil spring. In the sham group, the spring was not activated. Control group did
      not receive any appliance. At days 1, 3, 7, 14, and 28, the maxillae were
      collected for RNA and protein analysis, immunohistochemistry, and micro-CT.
      RESULTS: There was a linear relation between the force and the level of cytokine
      expression at lower magnitudes of force. Higher magnitudes of force did not
      increase the expression of cytokines. Activity of CCL2, CCL5, IL-1, TNF-alpha,
      RANKL, and number of osteoclasts reached a saturation point in response to higher
      magnitudes of force, with unchanged rate of tooth movement. CONCLUSION: After a
      certain magnitude of force, there is a saturation in the biological response, and
      higher forces do not increase inflammatory markers, osteoclasts, nor the amount
      of tooth movement. Therefore, higher forces to accelerate the rate of tooth
      movement are not justified.

PMID- 25865530
TI  - 3D superimposition and understanding temporomandibular joint arthritis.
AB  - OBJECTIVES: To investigate the 3D morphological variations in 169
      temporomandibular ioint (TMJ) condyles, using novel imaging statistical modeling
      approaches. SETTING AND SAMPLE POPULATION: The Department of Orthodontics and
      Pediatric Dentistry at the University of Michigan. Cone beam CT scans were
      acquired from 69 subjects with long-term TMJ osteoarthritis (OA, mean age 39.1+/
      15.7 years), 15 subjects at initial consult diagnosis of OA (mean age 44.9+/-14.8
      years), and seven healthy controls (mean age 43+/-12.4 years). MATERIALS AND
      METHODS: 3D surface models of the condyles were constructed, and homologous
      correspondent points on each model were established. The statistical framework
      included Direction-Projection-Permutation (DiProPerm) for testing statistical
      significance of the differences between healthy controls and the OA groups
      determined by clinical and radiographic diagnoses. RESULTS: Condylar morphology
      in OA and healthy subjects varied widely with categorization from mild to severe
      bone degeneration or overgrowth. DiProPerm statistics supported a significant
      difference between the healthy control group and the initial diagnosis of OA
      group (t=6.6, empirical p-value=0.006) and between healthy and long-term
      diagnosis of OA group (t=7.2, empirical p-value=0). Compared with healthy
      controls, the average condyle in OA subjects was significantly smaller in all
      dimensions, except its anterior surface, even in subjects with initial diagnosis
      of OA. CONCLUSION: This new statistical modeling of condylar morphology allows
      the development of more targeted classifications of this condition than
      previously possible.

PMID- 25865531
TI  - Mechanical environment change in root, periodontal ligament, and alveolar bone in
      response to two canine retraction treatment strategies.
AB  - OBJECTIVE: To investigate the initial mechanical environment (ME) changes in root
      surface, periodontal ligament (PDL), and alveolar bone due to two treatment
      strategies, low or high moment-to-force ratio (M/F). SETTING AND SAMPLE
      POPULATION: Indiana University-Purdue University Indianapolis. Eighteen patients
      who underwent maxillary bilateral canine retraction. MATERIAL AND METHOD: Finite
      element models of the maxillary canines from the patients were built based on
      their cone beam computed tomography scans. For each patient, the canine on one
      side had a specially designed T-loop spring with the M/F higher than the other
      side. Four stress invariants (1st principal/dilatational/3rd principal/von Mises
      stress) in the tissues were calculated. The stresses were compared with the bone
      mineral density (BMD) changes reported previously for linking the ME change to
      bone modeling/remodeling activities. The correlation was tested by the mixed
      model anova. RESULTS: The alveolar bone in the direction of tooth movement is
      primarily in tension, while the PDL is in compression; the stresses in the
      opposite direction have a reversed pattern. The M/F primarily affects the stress
      in root. Three stress invariants (1st principal/3rd principal/dilatational
      stress) in the tooth movement direction have moderate correlations with BMD loss.
      CONCLUSIONS: The stress invariants may be used to characterize what the
      osteocytes sense when ME changes. Their distributions in the tissues are
      significantly different, meaning the cells experience different stimuli. The
      higher bone activities along the direction of tooth movement may be related to
      the initial volumetric increase and decrease in the alveolar bone.

PMID- 25865532
TI  - Mandibular distraction osteogenesis assisted by cell-based tissue engineering: a
      systematic review.
AB  - OBJECTIVES: To review the advances and limitations of recent investigations on
      mandibular distraction osteogenesis (MDO) assisted by mesenchymal stem cell (MSC)
      transplantation. MATERIALS AND METHODS: Following the preferred reporting items
      for systematic reviews and meta-analysis (PRISMA) guidelines, the PubMed, Scopus,
      and Cochrane electronic databases were systematically searched and screened from
      their inception through August 2014. Searching terms included the following:
      'distraction osteogenesis', 'mandible OR mandibular OR jaw', and 'cells', without
      any other limitations. RESULTS: Nineteen studies meeting the eligibility criteria
      were selected from 227 published articles and used for qualitative synthesis.
      Fifteen of the studies used small animal models (rats or rabbits), while the
      other four used large animal models (dogs, pigs or sheep). Among these studies,
      large variations exist in MDO protocol, cell transplantation time, route and
      quantity, as well as methodology of outcome assessment. Additionally, all studies
      had certain biases. Nevertheless, the majority of studies found that MSC
      transplantation enhanced MDO bone regeneration. CONCLUSION: Evidence from animal
      studies indicates that MDO may be enhanced by mesenchymal stem cell
      transplantation, but many questions related to animal models, MDO protocols, and
      cell transplantation remain to be investigated.

PMID- 25865534
TI  - Characterization of short root anomaly in a Mexican cohort--hereditary idiopathic
      root malformation.
AB  - OBJECTIVE: The purpose of this study was to systematically characterize
      individuals with short root anomaly (SRA) without any history of orthodontic
      treatment. The long-term objective of the study was to improve diagnosis and
      treatment planning and determine risk factors for developing SRA. SETTING AND
      SAMPLE POPULATION: Twenty-seven patients including two families and 16 unrelated
      individuals from (9-48 years) reported to orthodontic and/or dental practitioners
      within the USA. MATERIALS AND METHODS: Digital panoramic and periapical films
      were analyzed to document pattern and frequency of SRA-affected teeth. Crown-to
      root (CR) ratios of the affected teeth were used to characterize the extent of
      malformation. Pedigree analysis by inspection was completed for one family to
      determine pattern of inheritance. RESULTS: Twenty-six of the twenty-seven
      individuals were of Latino descent, and one was of Filipino descent. Hard tissues
      including enamel, dentin, pulp chambers and canals, and surrounding soft tissues
      were normal. We found that 25 of 27 individuals had localized SRA and two Latino
      individuals had generalized SRA. Teeth were affected bilaterally with maxillary
      central incisors (~63%) and mandibular second premolars most commonly involved
      (~33%). Affected teeth had a distinct, similar radiographic appearance; in the
      generalized cases, there was a more severe affection with larger (~twice) CR
      ratios. Ninety-four percent of affected individuals did not show a significant
      difference in the CR ratios at different ages. Pedigree analysis suggests an
      autosomal dominant inheritance pattern in one family. CONCLUSION: This is the
      first report to show that SRA occurs more frequently in Latino individuals and
      has a predilection for anterior teeth. The occurrence of SRA in two families
      further confirms a hereditary component and supports a distinct nosology and
      nomenclature, hereditary idiopathic root malformation (HIRM) and warrants further
      investigation.

PMID- 25865533
TI  - Visible red and infrared light alters gene expression in human marrow stromal
      fibroblast cells.
AB  - OBJECTIVES: This study tested whether or not gene expression in human marrow
      stromal fibroblast (MSF) cells depends on light wavelength and energy density.
      MATERIALS AND METHODS: Primary cultures of isolated human bone marrow stem cells
      (hBMSC) were exposed to visible red (VR, 633 nm) and infrared (IR, 830 nm)
      radiation wavelengths from a light emitting diode (LED) over a range of energy
      densities (0.5, 1.0, 1.5, and 2.0 Joules/cm2) Cultured cells were assayed for
      cell proliferation, osteogenic potential, adipogenesis, mRNA and protein content.
      mRNA was analyzed by microarray and compared among different wavelengths and
      energy densities. Mesenchymal and epithelial cell responses were compared to
      determine whether responses were cell type specific. Protein array analysis was
      used to further analyze key pathways identified by microarrays. RESULT: Different
      wavelengths and energy densities produced unique sets of genes identified by
      microarray analysis. Pathway analysis pointed to TGF-beta 1 in the visible red
      and Akt 1 in the infrared wavelengths as key pathways to study. TGF-beta protein
      arrays suggested switching from canonical to non-canonical TGF-beta pathways with
      increases to longer IR wavelengths. Microarrays suggest RANKL and MMP 10 followed
      IR energy density dose-response curves. Epithelial and mesenchymal cells respond
      differently to stimulation by light suggesting cell type-specific response is
      possible. CONCLUSIONS: These studies demonstrate differential gene expression
      with different wavelengths, energy densities and cell types. These differences in
      gene expression have the potential to be exploited for therapeutic purposes and
      can help explain contradictory results in the literature when wavelengths, energy
      densities and cell types differ.

PMID- 25865535
TI  - Genetic and treatment-related risk factors associated with external apical root
      resorption (EARR) concurrent with orthodontia.
AB  - OBJECTIVE: As genetic variation accounts for two-thirds of the variation in
      external apical root resorption (EARR) concurrent with orthodontic treatment, we
      analyzed the association of selected genetic and treatment-related factors with
      EARR concurrent with orthodontic treatment. SETTING AND SAMPLE POPULATION: This
      case-control study of 134 unrelated, orthodontically treated Caucasian
      individuals was conducted in part at an Indiana Private Practice, Indiana
      University and the University of Kentucky. METHODS: Utilizing a research data
      bank containing information from ~1450 orthodontically treated patients, pre- and
      post-treatment radiographs from 460 individuals were evaluated for EARR of the
      four permanent maxillary incisors. Sixty-seven unrelated Caucasians with moderate
      to severe EARR were identified and were age-/sex-matched with orthodontically
      treated Caucasian controls yielding 38 females and 29 males per group. Factors
      tested for an association with EARR included the following: 1) treatment
      duration, 2) extraction of maxillary premolars, 3) numerous cephalometric
      measurements, and 4) DNA polymorphisms within/near candidate genes in a pathway
      previously implicated in EARR such as the purinergic-receptor-P2X, ligand-gated
      ion channel 7 (P2RX7; rs208294, rs1718119, and rs2230912), caspase-1 (CASP1;
      rs530537, rs580253, and rs554344), interleukin-1 beta (IL1B; rs1143634),
      interleukin-1 alpha (IL1A; rs1800587), and interleukin-1 receptor antagonist
      (IL1RA; rs419598) genes. Stepwise logistic regression was utilized to identify
      the factors significantly associated (significance taken at or less than the
      layered Bonferroni correction alpha) with the occurrence of EARR. RESULTS: A long
      length of treatment and the presence of specific genotypes for P2RX7 SNP rs208294
      were significantly associated with EARR. CONCLUSION: EARR occurrence was
      associated with both genetic and treatment-related variables, which together
      explained 25% of the total variation associated with EARR in the sample tested.

PMID- 25865536
TI  - Management of sleep apnea: a critical look at intra-oral appliances.
AB  - With so many disciplines of both medicine and dentistry involved in the treatment
      of obstructive sleep apnea (OSA), several forms of therapy are available. The
      orthodontist is rarely considered when the diagnosis of chronic obstructive sleep
      apnea (OSA) is delivered. However, the scope of orthodontic care today is much
      broader than the mere alignment of teeth. While the current gold standard for OSA
      care remains continuous positive air pressure (CPAP), the patient may be given a
      prescription for an intra-oral sleep appliance. When orthodontists work in
      concert with their medical colleagues to provide a sleep appliance, several
      considerations must be made including the evidence regarding oral appliance
      efficacy. For some patients, oral appliances are highly successful; however, even
      for responsive patients, there are risks associated with oral appliance therapy.
      The aim of the paper was to present a critical review of the current level of
      evidence for the use of oral appliances in the treatment of OSA. A substantial
      number of publications ranging from case reports, uncontrolled and controlled
      case series, prospective randomized studies, and even a small number of
      systematic reviews were available. The existing systematic reviews were based on
      either a limited number of prospective studies with limited numbers of patients
      or in some cases were based on subjective data only. As a result, a narrative
      review of the literature was performed that discusses objective clinically
      testable criteria and recent developments that may aid future research
      investigations. 

PMID- 25865537
TI  - Genetics of the dentofacial variation in human malocclusion.
AB  - Malocclusions affect individuals worldwide, resulting in compromised function and
      esthetics. Understanding the etiological factors contributing to the variation in
      dentofacial morphology associated with malocclusions is the key to develop novel
      treatment approaches. Advances in dentofacial phenotyping, which is the
      comprehensive characterization of hard and soft tissue variation in the
      craniofacial complex, together with the acquisition of large-scale genomic data
      have started to unravel genetic mechanisms underlying facial variation. Knowledge
      on the genetics of human malocclusion is limited even though results attained
      thus far are encouraging, with promising opportunities for future research. This
      review summarizes the most common dentofacial variations associated with
      malocclusions and reviews the current knowledge of the roles of genes in the
      development of malocclusions. Lastly, this review will describe ways to advance
      malocclusion research, following examples from the expanding fields of phenomics
      and genomic medicine, which aim to better patient outcomes. 

PMID- 25865538
TI  - Phenotype-genotype correlations of facial width and height proportions in
      patients with Class II malocclusion.
AB  - OBJECTIVES: To characterize soft-tissue facial height and width variation in
      Class II malocclusion and test for correlations with genes HMGA2, AJUBA, and ADK.
      SETTING AND SAMPLE POPULATION: Nine facial proportions were estimated from 2D
      frontal repose photographs of 330 Caucasian adults with Class II malocclusion.
      MATERIAL AND METHODS: After adjustments for age and gender, the facial
      proportions were submitted to a principal component analyses (PCA). The most
      meaningful phenotypic variations were correlated with SNPs rs7924176 (ADK),
      rs17101923 (HMGA2), and rs997154 (AJUBA) genotyped in 106 individuals. RESULTS:
      Principal component analyses resulted in four principal components (PCs), which
      explained 75% of total variation. PC1 captured variation in the intercanthus
      distance and explained 28% of total variation. PC2 explained 21% of the
      variations in facial taper and facial index. PC3 explained 14% and reflected
      variations in the vertical dimension of the lower face. PC4 explained 12% and
      captured variations in distance between the eyes, width of the commissures, and
      the length of the superior aspect of the lower face height corresponding to the
      vertical dimension of the philtrum of the upper lip. A suggestive association
      (p<0.05) was observed between PC4 and rs997154 corroborating the role of AJUBA in
      variation of facial dimensions. CONCLUSION: 2D frontal photographs can be used to
      derive quantitative measures of soft-tissue phenotypes that are of clinical
      relevance. The methods described are suitable for discovery and replication of
      associations between genotypes and malocclusion phenotypes.

PMID- 25865539
TI  - Bone anchors--can you hitch up your wagon?
AB  - The purpose of this review was to address and understand the current status of
      mini-screw implants (MSI) that are used in orthodontics. Understanding the
      biologic adaptation of MSI to its adjacent bone is one of the critical factors to
      their success. The review explores factors that are associated with failure of
      MSI, with special focus on an understanding of osseointegration as it relates to
      MSI. The rationale and importance of measuring bone contact and dynamic bone
      remodeling in animal studies are outlined. The utility of microcomputed
      tomography (MUCT) as a substitute for conventional histomorphometry is debated.
      Finally, alveolar physiology and rigidity of implants are explored to understand
      potential reasons for the high failure rate of MSI when compared to endosseous
      implants. 

PMID- 25865540
TI  - Evaluation of three-dimensional root surface changes and resorption following
      rapid maxillary expansion: a cone beam computed tomography investigation.
AB  - OBJECTIVES: To evaluate root surface changes and resorption following toothborne
      rapid maxillary expansion (RME) using cone beam computed tomography (CBCT).
      SETTING AND SAMPLE POPULATION: The Department of Orthodontics at The University
      of Texas Health Science Center. Twenty-four consecutively treated patients (mean
      age: 12.8 years) requiring maxillary expansion. MATERIAL AND METHODS: An
      observational cohort included 48 CBCT images collected prior to (T1) and 4.8
      months after (T2) RME from the study sample. Maxillary (study group) and
      mandibular (control group) first molars (n=48) and first premolars (n=48) were
      segmented and digitally registered using a 'best-fit' algorithm. Linear surface
      and volumetric changes between the study and control groups were compared using
      independent sample t-tests. Additionally, individual root length measurements
      were compared between the T1 and T2 images in each group using paired t-tests.
      RESULTS: All study teeth had significant changes for the evaluation of maximum
      linear surface area and volumetric changes as compared to control teeth (p<0.05).
      On average, premolars and molars in the study group experienced a root shortening
      of 0.36-0.52 mm (p<0.05). Color-coded diagrams demonstrated thinning and
      resorption occurring primarily at the apex and buccal aspects of the roots.
      Severity of these changes was individual-specific, as root resorption patterns
      were non-uniform. CONCLUSION: Significant volume loss, linear surface area
      changes, and thinning/shortening of maxillary first molar and premolar roots were
      common findings with the use of toothborne RME therapy.

PMID- 25865541
TI  - Accuracy of alveolar bone measurements from cone beam computed tomography
      acquired using varying settings.
AB  - OBJECTIVES: To investigate the accuracy and reliability of cone beam computed
      tomography (CBCT) measurements of buccal alveolar bone height (BBH) and thickness
      (BBT) using custom acquisition settings. SETTINGS AND SAMPLE POPULATION: School
      of Dentistry, Oregon Health & Science University. Twelve embalmed cadavers.
      MATERIALS AND METHODS: Cadaver heads were imaged by CBCT (i-CAT(r) 17-19, Imaging
      Sciences International, Hatfield, PA) using a 'long scan' (LS) setting with 619
      projection images, 360 degrees  revolution, 26.9 s duration, and 0.2 mm voxel
      size, and using a 'short scan' (SS) setting with 169 projection images, 180
      degrees  rotation, 4.8 s duration, and 0.3 mm voxel size. BBH and BBT were
      measured with 65 teeth, indirectly from CBCT images and directly through
      dissection. Comparisons were assessed using paired t-tests (p<=0.05). Level of
      agreement was assessed by concordance correlation coefficients, Pearson's
      correlation coefficients, and Bland-Altman plots. RESULTS: Mean differences in
      measurements compared to direct measurements were as follows, LS 0.17+/-0.12
      (BBH) and 0.10+/-0.07 mm (BBT), and SS 0.41+/-0.32 (BBH) and 0.12+/-0.11 mm
      (BBT). No statistical differences were found with any of BBH or BBT measurements.
      Correlation coefficients and Bland-Altman plots showed agreement was high between
      direct and indirect measurement methods, although agreement was stronger for
      measurements of BBH than BBT. CONCLUSIONS: Compared to the LS, the similarity in
      results with the reduced scan times and hence reduced effective radiation dose,
      favors use of shorter scans, unless other purposes for higher resolution imaging
      can be defined.

PMID- 25865542
TI  - Infield masticatory muscle activity in subjects with pain-related
      temporomandibular disorders diagnoses.
AB  - OBJECTIVES: Pain-related temporomandibular disorders (TMDs) are the most
      prevalent conditions among TMDs. There is contrasting evidence available for
      association of pain-related TMD and masticatory muscle activity (MMA). The
      present investigation assesses the associations between MMA levels of masseter
      and temporalis muscles during awake and sleep among pain-related TMD diagnostic
      groups. SETTING AND SAMPLE POPULATION: The department of Oral Diagnostic
      Sciences, University at Buffalo. Twenty females and six males participated in
      this study. MATERIAL AND METHODS: Using the diagnostic criteria for
      temporomandibular disorders (DC-TMDs), participants were diagnostically
      categorized. Subjects used a custom monitoring system, which recorded infield
      muscle activities. A factorial model tested for association between independent
      variable (muscle, time period, MMA level, and diagnostic group) effects and the
      logarithm of MMA. Greenhouse-Geisser test was used to determine any statistically
      significant associations (p<=0.003). RESULTS: No statistically significant
      association was found between four-way, three-way, and two-way analyses. However,
      among the main effects, range of magnitudes was the only variable to be
      statistically significant. Although the data suggest a trend of increased
      masseter MMA in the pain-related TMD diagnoses group both during awake and sleep
      time periods, such observation is not maintained for the temporalis muscle. In
      addition, temporalis MMA was found to be higher in the pain-related TMD diagnoses
      group only at extreme activity levels (<25 and >=80% ranges). CONCLUSION: This
      data support the association between masticatory muscle hyperactivity and painful
      TMD conditions.

PMID- 25865543
TI  - A pilot study of ambulatory masticatory muscle activities in temporomandibular
      joint disorders diagnostic groups.
AB  - OBJECTIVE: To determine differences in masticatory muscle usage between
      temporomandibular joint disorders diagnostic groups. SETTING AND SAMPLE
      POPULATION: Seventy-one informed and consented subjects (27 men; 44 women)
      participated at the University at Buffalo. MATERIAL AND METHODS: Research
      diagnostic criteria and imaging data were used to categorize subjects according
      to the presence/absence +/- of TMJ disc placement (DD) and chronic pain (P)
      (+DD+P, n=18; +DD-P, n=14; -DD-P, n=39). Electromyographic (EMG)/bite-force
      calibrations determined subject-specific masseter and temporalis muscle
      activities per 20 N bite-force (T20N , MUV). Over 3 days and nights, subjects
      collected EMG recordings. Duty factors (DFs, % of recording time) were determined
      based on threshold intervals (5-9, 10-24, 25-49, 50-79, >=80% T20N ). anova and
      Tukey-Kramer post hoc tests identified 1) diagnostic group differences in T20N
      and 2) the effects of diagnostic group, gender, time and interval on muscle DFs.
      RESULTS: Mean (+/-SE) temporalis T20N in +DD+P subjects was significantly higher
      (71.4+/-8.8 MUV) than masseter T20N in these subjects (19.6+/-8.8 MUV; p=0.001)
      and in -DD-P subjects (25.3+/-6.0 MUV, p=0.0007). Masseter DFs at 5-9% T20N were
      significantly higher in +DD-P women (3.48%) than +DD-P men (0.85%) and women and
      men in both other diagnostic groups (all p<0.03), and in +DD+P women (2.00%)
      compared to -DD-P men (0.83%; p=0.029). Night-time DFs at 5-9% T20N in +DD-P
      women (1.97%) were significantly higher than in -DD-P men (0.47%) and women
      (0.24%; all p<0.01). CONCLUSIONS: Between-group differences were found in
      masticatory muscle activities in both laboratory and natural environmental
      settings.

PMID- 25865544
TI  - Viscoelastic shear properties of porcine temporomandibular joint disc.
AB  - OBJECTIVES: To investigate the intrinsic viscoelastic shear properties in porcine
      TMJ discs. MATERIALS AND METHODS: Twelve fresh porcine TMJ discs from young adult
      pigs (6-8 months) were used. Cylindrical samples (5 mm diameter) with uniform
      thickness (~1.2 mm) were prepared from five regions of the TMJ disc. Torsional
      shear tests were performed under 10% compressive strain. Dynamic shear was
      applied in two methods: 1) a frequency sweep test over the frequency range of 0.1
      10 rad/s with a constant shear strain amplitude of 0.05 rad and 2) a strain sweep
      test over the range of 0.005-0.15 rad at a constant frequency of 10 rad/s.
      Transient stress relaxation tests were also performed to determine the
      equilibrium shear properties. RESULTS: As the frequency increased in the
      frequency sweep test, the dynamic shear complex modulus increased, with values
      ranging from 7 to 17 kPa. The phase angle, ranging from 11 to 15 degrees,
      displayed no pattern of regional variation as the frequency increased. The
      dynamic shear modulus decreased as the shear strain increased. The equilibrium
      shear modulus had values ranging from 2.6 to 4 kPa. The posterior region had
      significantly higher values for dynamic shear modulus than those in the anterior
      region, while no significant regional difference was found for equilibrium shear
      modulus. CONCLUSION: Our results suggest that the intrinsic region-dependent
      viscoelastic shear characteristics of TMJ disc may play a crucial role in
      determining the local strain of the TMJ disc under mechanical loading.

PMID- 25865545
TI  - Diagnostic group differences in temporomandibular joint energy densities.
AB  - OBJECTIVES: Cartilage fatigue, due to mechanical work, may account for precocious
      development of degenerative joint disease in the temporomandibular joint (TMJ).
      This study compared energy densities (mJ/mm3) in TMJs of three diagnostic groups.
      SETTING AND SAMPLE POPULATION: Sixty-eight subjects (44 women, 24 men) gave
      informed consent. Diagnostic criteria for temporomandibular disorders (DC/TMD)
      and imaging were used to group subjects according to presence of jaw muscle or
      joint pain (+P) and bilateral disk displacement (+DD). MATERIAL AND METHODS:
      Subjects (+P+DD, n=16; -P+DD, n=16; and -P-DD, n=36) provided cone-beam computed
      tomography and magnetic resonance images, and jaw-tracking data. Numerical
      modeling was used to determine TMJ loads (Fnormal). Dynamic stereometry was used
      to characterize individual-specific data of stress-field dynamics during 10
      symmetrical jaw-closing cycles. These data were used to estimate tractional
      forces (Ftraction). Energy densities were then calculated as W/Q (W=work done or
      mechanical energy input=tractional force*distance of stress-field translation,
      Q=volume of cartilage). anova and Tukey-Kramer post hoc analyses tested for
      intergroup differences. RESULTS: Mean+/-standard error energy density for the
      +P+DD group was 12.7+/-1.5 mJ/mm3 and significantly greater (all adjusted p<0.04)
      when compared to -P+DD (7.4+/-1.4 mJ/mm3) and -P-DD (5.8+/-0.9 mJ/mm3) groups.
      Energy densities in -P+DD and -P-DD groups were not significantly different.
      CONCLUSION: Diagnostic group differences in energy densities suggest that
      mechanical work may be a unique mechanism, which contributes to cartilage fatigue
      in subjects with pain and disk displacement.

PMID- 25865547
TI  - Ideal orthodontic alignment load relationships based on periodontal ligament
      stress.
AB  - OBJECTIVES: To test the hypothesis that periodontal ligament (PDL) stress
      relationships that yield resistance numbers representing load proportions between
      different teeth depend on alignment load type. MATERIALS AND METHODS: Finite
      element models of all teeth, except the third molars, were produced. Four
      different types of loads were applied, and the third principal stresses of
      different teeth in standardized areas of most compression were calculated. Based
      on these results, resistance numbers, representing the load proportions for each
      tooth derived from PDL stress, were determined. RESULTS: The third principal
      stress values for typical alignment loads in the areas of most stress were very
      different for different load types for each tooth. Differences in resistance
      numbers between teeth also varied with different loads. CONCLUSION: Resistance
      numbers, that is, load proportion numbers between teeth to achieve similar stress
      at the compressive PDL zone, depend on the type of applied load.

PMID- 25865546
TI  - Modeling of muscle forces in humans with and without temporomandibular joint
      disorders.
AB  - OBJECTIVES: Subjects with/without temporomandibular joint disorders (TMJD) were
      tested for differences in muscle forces. SETTING AND SAMPLE POPULATION: School of
      Dental Medicine, University at Buffalo. Ninety-one subjects were classified in
      four groups based on the presence/absence (+/-) of chronic myofascial and/or TMJ
      pain (P) and bilateral disc displacement (DD). MATERIAL AND METHODS: Validated
      numerical models employed an organizational objective and subjects' anatomy to
      calculate masticatory muscle forces during static biting. anova and Holm's step
      down procedure post hoc tests assessed group differences. Theoretical geometries,
      representing the range of subjects' muscle orientations, were surveyed via
      numerical models to identify key combinations resulting in high muscle forces.
      Effect size (Cohen's d) and anova/post hoc tests assessed group differences in
      key muscle orientations. RESULTS: +P-DD subjects had significantly higher muscle
      forces, especially for lateral pterygoid muscles, compared to the other groups
      (p<0.01) for bite forces that were directed posteromedially or posterolaterally
      on mandibular molars and posteriorly and slightly medially on mandibular
      incisors. Key muscle orientations for peak lateral pterygoid muscle forces were
      identified, and group comparisons showed mean orientation in +P-DD compared to
      other diagnostic groups was >=5 degrees  more upright for masseter and >=3
      degrees  more posteriorly directed for temporalis muscles (all Cohen's d>=0.8).
      CONCLUSION: Predicted lateral pterygoid muscle forces were significantly higher
      in +P-DD compared to other groups for specific biting conditions and were
      attributable, in part, to differences in masseter and temporalis muscle
      orientations.

PMID- 25865548
TI  - Locally limited inhibition of bone resorption and orthodontic relapse by
      recombinant osteoprotegerin protein.
AB  - OBJECTIVES: To determine minimal dose levels required for local inhibition of
      orthodontic relapse by recombinant OPG protein (OPG-Fc), while also determining
      effects of injected OPG-Fc on alveolar bone and long bone. SETTING AND SAMPLE
      POPULATION: The Department of Orthodontics and Pediatric Dentistry at the
      University of Michigan. Eighteen male Sprague Dawley rats. MATERIALS & METHODS:
      Maxillary molars were moved with nickel-titanium springs and then allowed to
      relapse in Sprague Dawley rats. Upon appliance removal, animals were injected
      with a single dose of 1.0 mg/kg OPG-Fc, 0.1 mg/kg OPG-Fc, or phosphate-buffered
      saline (vehicle) just distal to the molar teeth. Tooth movement measurements were
      made from stone casts, which were scanned and digitally measured. Alveolar
      tissues were examined by histology. Micro-computed tomography was used to
      quantify changes in alveolar and femur bone. RESULTS: Local injection of OPG-Fc
      inhibited molar but not incisor relapse, when compared to vehicle-injected
      animals. No significant differences in alveolar or femur bone were seen between
      the three treatment groups after 24 days of relapse. CONCLUSIONS: Our results
      demonstrate that a single local injection of OPG-Fc effectively inhibits
      orthodontic relapse, with minimal systemic bone metabolic effects. Our results
      also show that a single injection of OPG-Fc will influence tooth movement only in
      teeth close to the injection site. These findings indicate that OPG-Fc has
      potential as a safe and effective pharmacological means to locally control
      osteoclasts, for uses such as maintaining anchorage during orthodontic tooth
      movement and preventing orthodontic relapse in humans.

PMID- 25865550
TI  - Pushing the limits of signal resolution to make coupling measurement easier.
AB  - Probing scalar couplings are essential for structural elucidation in molecular
      (bio)chemistry. While the measurement of JHH couplings is facilitated by SERF
      experiments, overcrowded signals represent a significant limitation. Here, a new
      band selective pure shift SERF allows access to delta(1)H and JHH with an
      ultrahigh spectral resolution. 

PMID- 25865549
TI  - The effects of tissue-non-specific alkaline phosphatase gene therapy on
      craniosynostosis and craniofacial morphology in the FGFR2C342Y/+ mouse model of
      Crouzon craniosynostosis.
AB  - OBJECTIVES: Craniosynostosis, the premature fusion of cranial bones, has
      traditionally been described as a disease of increased bone mineralization.
      However, multiple mouse models of craniosynostosis display craniosynostosis
      simultaneously with diminished cranial bone volume and/or density. We propose an
      alternative hypothesis that craniosynostosis results from abnormal tissue
      mineralization through the downregulation of tissue-non-specific alkaline
      phosphatase (TNAP) enzyme downstream of activating mutations in FGFRs. MATERIAL
      AND METHODS: Neonatal Crouzon (FGFRC342Y/+) and wild-type (FGFR+/+) mice were
      injected with lentivirus to deliver a recombinant form of TNAP. Mice were
      sacrificed at 4 weeks postnatal. Serum was collected to test for alkaline
      phosphatase (AP), phosphorus, and calcium levels. Craniofacial bone fusion and
      morphology were assessed by micro-computed tomography. RESULTS: Injection with
      the TNAP lentivirus significantly increased serum AP levels (increased serum AP
      levels are indicative of efficient transduction and production of the recombinant
      protein), but results were variable and dependent upon viral lot and the litter
      of mice injected. Morphological analysis revealed craniofacial form differences
      for inferior surface (p=0.023) and cranial height (p=0.014) regions between TNAP
      lentivirus-injected and vehicle-injected Crouzon mice. With each unit increase in
      AP level, the odds of lambdoid suture fusion decreased by 84.2% and these results
      came close to statistical significance (p=0.068). CONCLUSION: These results
      suggest that TNAP deficiency may mediate FGFR2-associated craniosynostosis.
      Future studies should incorporate injection of recombinant TNAP protein, to avoid
      potential side effects and variable efficacy of lentiviral gene delivery.

PMID- 25865551
TI  - The effects of geography on survival in patients with oral cavity squamous cell
      carcinoma.
AB  - OBJECTIVE: To assess the survival outcomes of oral cavity squamous cell carcinoma
      (OCSCC) by differing geographical location. METHODS: Demographic, pathologic,
      treatment, and survival data was obtained from OCSCC patients from 1998-2010 in
      Alberta, Canada. 554 patients were included from 660 OCSCC patients. Overall,
      disease-specific, and disease-free survivals were estimated with Kaplan-Meier and
      Cox regression analyses. Patients were grouped by geographic locations. RESULTS:
      Patients from urban locations had improved overall, disease-specific, and disease
      free survival compared to rural locations (p<0.05). Two and five year estimates
      of overall survival were significantly higher in the urban cohort at 84% and 78%,
      versus rural with 48% and 44%, respectively (p<0.05). Disease-specific and
      disease-free survival rates were also superior in the urban group (p<0.05).
      Diagnosis to treatment time for all 3 geographical groups was not found to be
      statistically significant (p>0.05). CONCLUSION: This study shows that patients
      with OCSCC living in urban settings have improved survival compared to rural
      groups.

PMID- 25865552
TI  - Extra-pulmonary small cell carcinoma in the head and neck setting: the role of
      prophylactic cranial irradiation.
AB  - Head-and-neck small cell carcinoma (HN-SmCC) is a rare entity and there is
      limited data to support management decisions. The role of prophylactic cranial
      irradiation (PCI) remains controversial. A retrospective review of 21 consecutive
      HN-SmCCs was performed. No case received PCI. The 2-year overall survival, local,
      regional and distant control rates were 65%, 94%, 88%, and 76% respectively.
      Despite no patient receiving PCI, brain metastases were uncommon (n=2) and
      routine use of PCI is not justified in this population. 

PMID- 25865553
TI  - Racial disparities in squamous cell carcinoma of the oral tongue among women: a
      SEER data analysis.
AB  - OBJECTIVES: The incidence of oral tongue cancer (OTC) in the US is increasing in
      women. To understand this phenomenon, we examined factors influencing OTC
      incidence and survival. MATERIALS AND METHODS: We identified women diagnosed with
      OTC that were reported to the Surveillance, Epidemiology and End Results (SEER)
      program from 1973 to 2010. Incidence and survival rates were compared across
      metropolitan, urban and rural residential settings and several other demographic
      categories by calculating rate ratios (RRs) with the corresponding 95% confidence
      intervals (CIs). We examined changes in incidence of OTC across racial groups
      using joinpoint analyses since 1973, and assessed factors associated with
      survival. Patients diagnosed prior to 1988 were excluded from the survival
      analysis due to lack of data on treatment. RESULTS: OTC incidence in white
      females demonstrated a significant upward trend with 0.53 annual percentage
      change (APC) between 1973 and 2010. The change seems to be limited to white women
      under the age of 50years and appears to have become pronounced in the 1990s. For
      African Americans (AA) on the other hand, the incidence has decreased. Incidence
      estimates did not differ in metropolitan, small urban and rural setting. The 1-,
      5- and 10-year relative survival estimates were 86%, 63% and 54% for white women,
      and 76%, 46% and 33% for AA women. On multivariable analyses factors
      significantly associated with better survival included lower stage, younger age,
      married status, and receipt of surgical treatment, but not race. CONCLUSION: The
      racial disparity in OTC survival is evident, but may be attributable to the
      differences in stage at diagnosis as well as access to and receipt of care. As
      the incidence of OTC is increasing in young white women, identifying the risk
      factors in this group may lead to a better understanding of OTC causes.

PMID- 25865554
TI  - Swallowing outcomes and PEG dependence in head and neck cancer patients receiving
      definitive or adjuvant radiotherapy +/- chemotherapy with a proactive PEG: a
      prospective study with long term follow up.
AB  - OBJECTIVES: This study examined long term swallowing outcomes of a cohort of head
      and neck cancer (HNC) patients identified at high risk of experiencing
      significant side effects from cancer treatment and were provided with a proactive
      PEG. MATERIAL AND METHODS: Ninety-five HNC patients receiving definitive or
      adjuvant radiotherapy +/- chemotherapy were identified for proactive PEG
      placement using validated guidelines and followed for up to 3years. Functional
      swallowing status was recorded at regular time points and data were collected on
      PEG use and duration in situ. RESULTS: Mean duration of enteral feeding was
      125days. PEGs remained in situ for approximately 7months. PEG removal was
      achieved by 52% by 6months and 86% by 1year. Only 3 (3%) remained PEG dependent
      at 3years. Over half (55%) had resumed a full non-texture modified diet by PEG
      removal. CONCLUSION: Proactive PEG placement did not lead to high proportion of
      long term tube dependence in this high risk group and the majority achieved good
      swallowing outcomes.

PMID- 25865555
TI  - The dynamics of resource allocation and costs of reproduction in a sexually
      dimorphic, wind-pollinated dioecious plant.
AB  - Sexual dimorphism in resource allocation is expected to change during the life
      cycle of dioecious plants because of temporal differences between the sexes in
      reproductive investment. Given the potential for sex-specific differences in
      reproductive costs, resource availability may contribute to variation in
      reproductive allocation in females and males. Here, we used Rumex hastatulus, a
      dioecious, wind-pollinated annual plant, to investigate whether sexual dimorphism
      varies with life-history stage and nutrient availability, and determine whether
      allocation patterns differ depending on reproductive commitment. To examine if
      the costs of reproduction varied between the sexes, reproduction was either
      allowed or prevented through bud removal, and biomass allocation was measured at
      maturity. In a second experiment to assess variation in sexual dimorphism across
      the life cycle, and whether this varied with resource availability, plants were
      grown in high and low nutrients and allocation to roots, aboveground vegetative
      growth and reproduction were measured at three developmental stages. Males
      prevented from reproducing compensated with increased above- and belowground
      allocation to a much larger degree than females, suggesting that male
      reproductive costs reduce vegetative growth. The proportional allocation to
      roots, reproductive structures and aboveground vegetative growth varied between
      the sexes and among life-cycle stages, but not with nutrient treatment. Females
      allocated proportionally more resources to roots than males at peak flowering,
      but this pattern was reversed at reproductive maturity under low-nutrient
      conditions. Our study illustrates the importance of temporal dynamics in sex
      specific resource allocation and provides support for high male reproductive
      costs in wind-pollinated plants. 

PMID- 25865556
TI  - PTPN11/Shp2 overexpression enhances liver cancer progression and predicts poor
      prognosis of patients.
AB  - BACKGROUND & AIMS: We have previously reported that Shp2, a tyrosine phosphatase
      previously known as a pro-leukemogenic molecule, suppresses the initiation of
      hepatocellular carcinoma (HCC). However, the role of Shp2 in HCC progression
      remains obscure. METHODS: Shp2 expression was determined in human HCC using real
      time PCR, immunoblotting and immunohistochemistry. Clinical significance of Shp2
      expression was analyzed in 301 HCC tissues with clinico-pathological
      characteristics and follow-up information. Short hairpin RNA was utilized to
      investigate the function of Shp2 in hepatoma cell behavior. Role of Shp2 in HCC
      progression was monitored through nude mice xenograft assay. Kinase activity
      assay and co-immunoprecipitation were used for mechanism analysis. RESULTS:
      Elevated expression of Shp2 was detected in 65.9% (394/598) of human HCCs, and
      its levels were even higher in metastasized foci. Overexpression of Shp2
      correlated well with the malignant clinico-pathological characteristics of HCC
      and predicted the poor prognosis of patients. Interference of Shp2 expression
      suppressed the proliferation of hepatoma cells in vitro and inhibited the growth
      of HCC xenografts in vivo. Down-regulation of Shp2 attenuated the adhesion and
      migration of hepatoma cells and diminished metastasized HCC formation in mice.
      Our data demonstrated that Shp2 promotes HCC growth and metastasis by
      coordinately activating Ras/Raf/Erk pathway and PI3-K/Akt/mTOR cascade. Moreover,
      down-regulation of Shp2 enhanced the sensitivity of hepatoma cells upon sorafenib
      treatment, and patients with low Shp2 expression exhibited superior prognosis to
      sorafenib. CONCLUSIONS: Shp2 promotes the progression of HCC and may serve as a
      prognostic biomarker for patients.

PMID- 25865558
TI  - Severe contact esophagitis in a patient taking crizotinib: A case report.

PMID- 25865557
TI  - Histological response, pattern of tumor destruction and clinical outcome after
      neoadjuvant chemotherapy including bevacizumab or cetuximab in patients
      undergoing liver resection for colorectal liver metastases.
AB  - AIM: We investigated whether the type of antibody [bevacizumab (bev) or cetuximab
      (cet)] added to neoadjuvant combination chemotherapy before curative liver
      resection was associated with histological response, the pattern of tumor
      destruction and clinical outcome in patients with colorectal liver metastases
      (CLM). METHODS: We investigated 138 patients with KRAS wild-type status (codon
      12, 13 and 61) who received neoadjuvant chemotherapy including bev (n = 101) or
      cet (n = 37). The primary endpoint was histological response. Secondary endpoints
      were necrosis and fibrosis of metastases, radiological response, recurrence-free
      survival (RFS) and overall survival (OS). RESULTS: Histological response was not
      significantly different between the two groups (P = 0.19). A significantly higher
      fraction of patients in the bev group showed necrosis of the metastases of >= 50%
      (P < 0.001), while a higher fraction of patients in the cet group showed fibrosis
      of >= 40% (P = 0.030). Radiological response was not significantly different (P =
      0.17). Median RFS was significantly shorter in the cet group in univariable
      analysis (HR 1.59 (95% CI 1.00, 2.51), P = 0.049), but this difference did not
      remain significant in multivariable analysis (P = 0.45). The 3-year OS rate was
      not significantly different (P = 0.73). CONCLUSIONS: The addition of bevacizumab
      to combination chemotherapy showed more necrosis but less fibrosis of metastases
      compared to cetuximab and a trend towards higher histological and radiological
      response and longer RFS. Further investigations of biological tumor
      characteristics are required to individualize treatment combinations.

PMID- 25865559
TI  - Hall effect of triplons in a dimerized quantum magnet.
AB  - SrCu2(BO3)2 is the archetypal quantum magnet with a gapped dimer-singlet ground
      state and triplon excitations. It serves as an excellent realization of the
      Shastry-Sutherland model, up to small anisotropies arising from Dzyaloshinskii
      Moriya interactions. Here we demonstrate that these anisotropies, in fact, give
      rise to topological character in the triplon band structure. The triplons form a
      new kind of Dirac cone with three bands touching at a single point, a spin-1
      generalization of graphene. An applied magnetic field opens band gaps resulting
      in topological bands with Chern numbers +/-2. SrCu2(BO3)2 thus provides a
      magnetic analogue of the integer quantum Hall effect and supports topologically
      protected edge modes. At a threshold value of the magnetic field set by the
      Dzyaloshinskii-Moriya interactions, the three triplon bands touch once again in a
      spin-1 Dirac cone, and lose their topological character. We predict a strong
      thermal Hall signature in the topological regime. 

PMID- 25865560
TI  - Tunable Conformation-Dependent Engineered Protein.Gold Nanoparticle
      Nanocomposites.
AB  - We demonstrate the fabrication of protein.gold nanoparticle (AuNP) nanocomposites
      in situ, leading to distinct assemblies dependent upon protein secondary
      structure. In the presence of pentameric coiled-coil proteins C and Q, which
      contain histidine tags and have helicities of 54 and 65%, respectively,
      templation of AuNP results in precipitation of the protein.AuNP composites with
      AuNPs 6.5 nm in diameter, creating macromolecular assemblies on the micrometer
      scale. In the absence of the histidine tags, the resulting Cx and Qx proteins,
      which exhibit lower helicities of 37 and 45%, respectively, stabilize soluble
      protein.AuNP composites with AuNPs 4.5 nm in diameter for several days without
      aggregating. By manipulating protein structure via external triggers, such as
      TFE, we obtain control over the macromolecular conformation and overall
      physicochemical properties. These hybrid protein.AuNP assemblies can be readily
      deposited on electrodes, where they can serve as a tunable bionanocomposite
      kinetic barrier. 

PMID- 25865561
TI  - The effect of canola meal tannins on the intestinal absorption capacity of
      broilers using a D-xylose test.
AB  - In three D-xylose absorption experiments, the effect of 1% HCl/methanol, 70%
      methanol or 70% acetone extracts of canola meal (CM) or 70% acetone extract of
      soybean meal (SBM) containing polyphenols, phenolic acids, tannins and phytic
      acid on intestinal absorption capacity of broilers was determined. In Exp. 1, the
      experimental groups received orally D-xylose solution alone or with methanol/HCl,
      methanol or acetone extracts of CM. In Exp. 2, the experimental groups received D
      xylose alone or with acetone extracts of CM or SBM. In Exp. 3, the experimental
      groups received D-xylose plus sucrose solution or D-xylose plus acetone extracts
      of CM or SBM. In Exps. 2 and 3, the CM extracts contained 2.7 and 2.6, 2.4 and
      2.3, 3.2 and 3.2, and 2.4 and 2.2 times higher polyphenols, phenolic acids,
      tannins and condensed tannins than the corresponding SBM extracts respectively.
      Blood samples were collected in 40-min intervals, and plasma D-xylose was
      measured. Compared to the Control, plasma D-xylose in Exp. 1 was lower (p <
      0.001) by 81, 69 and 73% at 40-min, by 41, 44 and 37% at 80-min and by 22, 31,
      and 23% at 120-min post-ingestion of the HCl/methanol, methanol and acetone
      extracts respectively. In both Exps. 2 and 3, plasma D-xylose level was lower (p
      < 0.001) in groups dosed with CM extract or SBM extract at each time of blood
      collection, when compared to the respective Control group. However, in Exp. 3,
      birds dosed with SBM extract had higher plasma D-xylose than CM extract-dosed
      birds by 28, 8 and 21% at 40, 80 and 120 min respectively (p < 0.01). In
      conclusion, although CM extract caused a lower absorption of D-xylose, based on 5
      to 10% of CM inclusion levels in practical broiler rations, the soluble bioactive
      components of CM will likely have minor impact on the absorption capacity of the
      chicken intestine.

PMID- 25865562
TI  - Erratum to: Increased bioavailability of phenylephrine by co-administration of
      acetaminophen: results of four open-label, crossover pharmacokinetic trials in
      healthy volunteers.

PMID- 25865563
TI  - Using pictograms to assist caregivers in liquid medication administration: a
      systematic review.
AB  - WHAT IS KNOWN AND OBJECTIVE: It has been reported that more than 80% of out-of
      hospital medication errors among the young children involve liquid formulations.
      The usefulness of pictorial aids to improve communication of medication
      instructions has not been extensively investigated for child health. The
      objective of this study was to determine the effectiveness of pictorial aids used
      to assist caregivers in the administration of liquid medications. METHODS:
      MEDLINE, CINAHL, PsycINFO, ScienceDirect, Scopus and the Cochrane Library were
      searched for articles published up to February 2015. Studies that used pictorial
      aids with liquid medications and measured at least one of the following outcomes
      were included: dosing accuracy, comprehension of medication instructions, recall
      of information and adherence of caregivers. Two authors independently selected
      studies, extracted data and assessed methodological quality of studies using the
      Cochrane Collaboration's tool. RESULTS AND DISCUSSION: Five experimental studies
      (four hospital based and one community based) with a total of 962 participants
      were included. A wide range of liquid formulations were studied, including both
      prescription and over-the-counter medications. The existing findings suggest that
      pictographic interventions reduced dosing errors, enhanced comprehension and
      recall of medication instructions and improved adherence of caregivers.
      Incorporating pictorial aids into verbal medication counselling or text-based
      instructions was more beneficial than using the single approach alone. Mixed
      results were identified for the relationship between health literacy of
      caregivers and effectiveness of pictorial aids. WHAT IS NEW AND CONCLUSION: The
      evidence remains limited due to the small number of studies found and variations
      in methodological quality. This review suggests that pictorial aids might be
      potential interventions, but more high-quality studies are needed to support the
      routine use of any pictogram-based materials with liquid medications in the
      clinical settings.

PMID- 25865566
TI  - Urea homogeneous nucleation mechanism is solvent dependent.
AB  - The composition of the mother phase plays a primary role in crystallization
      processes, affecting both crystal nucleation and growth. In this work, the
      influence of solvents on urea nucleation has been investigated by means of
      enhanced sampling molecular dynamics simulations. We find that, depending on the
      solvent, the nucleation process can either follow a single-step or a two-step
      mechanism. While in methanol and ethanol a single-step nucleation process is
      favored, in acetonitrile a two-step process emerges as the most likely nucleation
      pathway. We also find that solvents have a minor impact on polymorphic
      transitions in the early stages of urea nucleation. The impact of finite size
      effects on the free energy surfaces is systematically considered and discussed in
      relation to the simulation setup. 

PMID- 25865565
TI  - Hepatic ALT isoenzymes are elevated in gluconeogenic conditions including
      diabetes and suppressed by insulin at the protein level.
AB  - BACKGROUND: Alanine transaminase (ALT) plays an important role in gluconeogenesis
      by converting alanine into pyruvate for glucose production. Early studies have
      shown that ALT activities are upregulated in gluconeogenic conditions and may be
      implicated in the development of diabetes. ALT consists of two isoforms, ALT1 and
      ALT2, with distinctive subcellular and tissue distributions. Whether and how they
      are regulated are largely unknown. METHODS: By using Western blotting analysis,
      we measured hepatic ALT isoforms at the protein level in obese and diabetic
      animals and in Fao hepatoma cells treated with dexamethasone and insulin. In
      addition, we measured glucose output in Fao cells over-expressing ALT1 and ALT2.
      RESULTS: Both ALT isoforms in the liver were increased in diabetic Goto-Kakizaki
      rats and during fasting. However, in ob/ob mice, only ALT2, but not ALT1, protein
      levels were elevated, and the increase of ALT2 was correlated with that of ALT
      activity. We further demonstrated that, in vitro, both ALT1 and ALT2 were induced
      by glucocorticoid dexamethasone, but suppressed by insulin in Fao cells. Finally,
      we showed that the over-expression of ALT1 and ALT2 in Fao cells directly
      increased glucose output. CONCLUSIONS: We have shown the similarity and
      difference in the regulation of ALT isoforms in gluconeogenic conditions at the
      protein level, supporting that ALT isoenzymes play an important role in glucose
      metabolism and may be implicated the development of insulin resistance and
      diabetes.

PMID- 25865567
TI  - Adverse childhood experiences: how schools can help.

PMID- 25865568
TI  - Herceptin conjugated PLGA-PHis-PEG pH sensitive nanoparticles for targeted and
      controlled drug delivery.
AB  - A dual functional nano-scaled drug carrier, comprising of a targeting ligand and
      pH sensitivity, has been made in order to increase the specificity and efficacy
      of the drug delivery system. The nanoparticles are made of a tri-block copolymer,
      poly(d,l lactide-co-glycolide) (PLGA)-b-poly(l-histidine) (PHis)-b-polyethylene
      glycol (PEG), via nano-precipitation. To provide the nanoparticle feature of
      endolysosomal escape and pH sensitivity, poly(l-histidine) was chosen as a proton
      sponge polymer. Herceptin, which specifically binds to HER2 antigen, was
      conjugated to the nanoparticles through click chemistry. The nanoparticles were
      characterized via dynamic light scattering (DLS) and transmission electron
      microscopy (TEM). Both methods showed the sizes of about 100nm with a uniform
      size distribution. The pH sensitivity was assessed by drug releases and size
      changes at different pH conditions. As pH decreased from 7.4 to 5.2, the drug
      release rate accelerated and the size significantly increased. During in vitro
      tests against human breast cancer cell lines, MCF-7 and SK-BR-3 showed
      significantly increased uptake for Herceptin-conjugated nanoparticles, as
      compared to non-targeted nanoparticles. Herceptin-conjugated pH-sensitive
      nanoparticles showed the highest therapeutic effect, and thus validated the
      efficacy of a combined approach of pH sensitivity and active targeting. 

PMID- 25865569
TI  - Development of mucoadhesive microbeads using thiolated sodium alginate for
      intrapocket delivery of resveratrol.
AB  - Resveratrol (Res), a polyphenolic phytoalexin, had shown a promising therapeutic
      efficacy towards treatment of periodontal disease in vitro. This work aims to
      develop Res microbeads with strong mucoadhesion using thiolated alginate (TA) for
      local treatment of periodontal pockets. TA was synthesized by conjugating sodium
      alginate (A) with thioglycolic acid. Product was evaluated by IR and DSC. Both A
      and A:TA Res microbeads with different ratios were prepared by ionotropic
      gelation method. Formulations were evaluated regarding their entrapment
      efficiency (%EE), swelling index (SI), in vitro drug release and kinetics.
      Selected formula was examined for its mucoadhesion by ex vivo wash-off method,
      surface morphology using scanning electron microscope (SEM) and stability against
      light. Clinical evaluation is running.Formation of TA was confirmed. %EE for all
      formulations ranged from 83.72 to 104.54%. Results revealed a significant lower
      SI for TA rich formulation (A/TA 1:1) along with slower release rate and zero
      order kinetics, in addition to powerful mucoadhesion; 26% remaining of microbeads
      after 1h, compared to 2% for A microbeads. SEM micrographs showed a rough surface
      with drug precipitation. The formula maintained its %EE after 5h exposure to
      direct sunlight. A/TA 1:1 mucoadhesive Res microbeads could be exploited as a
      prolonged drug release devices for intrapocket application. 

PMID- 25865570
TI  - A micelle-like structure of poloxamer-methotrexate conjugates as nanocarrier for
      methotrexate delivery.
AB  - The purpose of this study was to develop a novel featured and flexible
      methotrexate (MTX) formulation, in which MTX was physically entrapped and
      chemically conjugated in the same drug delivery system. A series of poloxamer-MTX
      (p-MTX) conjugates was synthesized, wherein MTX was grafted to poloxamer through
      an ester bond. p-MTX conjugates could self-assemble into micelle-like structures
      in aqueous environment and the MTX end was in the inner-core of micelles.
      Moreover, free MTX could be physically entrapped into p-MTX micelles hydrophobic
      core region to increase the total drug loading. Importantly, the resulting MTX
      loaded p-MTX micelles showed a biphasic release of MTX, with a relative fast
      release of the entrapped MTX (about 6-7h) followed by a sustained release of the
      conjugated MTX. The pharmacokinetics study showed that the mean residence time
      (MRT) was extended in the case of MTX-loaded p-MTX micelles, indicating a delayed
      MTX elimination from the bloodstream and prolonged in vivo residence time.
      Besides, the area under curve (AUC) of MTX-loaded p-MTX micelles was greater than
      free MTX, indicating a drug bioavailability improvement. Overall, MTX-loaded p
      MTX micelles might be a promising nanosized drug delivery system for the cancer
      therapy. 

PMID- 25865571
TI  - Controlled delivery of valsartan by cross-linked polymeric matrices: Synthesis,
      in vitro and in vivo evaluation.
AB  - The purpose of study was to develop chemically cross-linked chitosan-co
      poly(AMPS) hydrogel based on low molecular weight chitosan for pH-responsive and
      controlled drug delivery of a model drug. Cross-linking was achieved chemically,
      by using free radical polymerization technique. Polymer (low molecular weight
      chitosan) was chemically cross-linked with monomer (2-acrylamido-2-methylpropane
      sulfonic acid) in aqueous medium. N, N'-Methylenebisacrylamide (MBA) was used as
      cross-linking agent. Sodium hydrogen sulfite (SHS) and ammonium peroxodisulphate
      (APS) were used as initiators in a chemical reaction. Hydrogels were
      characterized by FT-IR, SEM and DSC. Swelling studies and pH-sensitivity of
      hydrogels were studies at pH 1.2 and 7.4. Chitosan-co-poly(AMPS) hydrogels were
      administered to rabbits orally to evaluate its pharmacokinetic behavior. As a
      result of successful cross-linking of polymer and monomer, novel co-polymer has
      been developed, having suitable characteristics as desired for controlled release
      drug delivery system. Maximum swelling, drug loading and release have been
      observed at pH 7.4. In vivo results exhibited significant drug release and
      absorption at pH 7.4 in rabbits. It is concluded that highly swelling chitosan
      AMPS based hydrogels were developed having pH independent swelling and pH
      dependent drug release properties. These hydrogels have great potential to be
      used for loading and controlled release of various therapeutic agents. 

PMID- 25865572
TI  - Body mass index and cognitive function: birth cohort effects in young men.
AB  - OBJECTIVE: Body mass index (BMI) and intelligence quotient (IQ) are associated.
      We examined whether this association varied by birth cohort. METHODS: Among
      37,414 Danish conscripts, the association between BMI and IQ overall and by birth
      cohort was examined. IQ was measured by the Borge Prien's Prove (BPP) group
      intelligence test score. RESULTS: Compared with men of normal BMI, mean
      differences (95% CI [confidence interval]) in BPP score were -0.6 (-1.1;-0.1) for
      underweight men; -0.8 (-1.1;-0.5) for overweight men; and -2.0 (-2.4;-1.5) for
      men with obesity. Crude prevalence ratios (95% CI) for low cognitive scores
      associated with obesity were, respectively, 1.52 (1.24; 1.85), 1.64 (1.32; 2.04),
      1.56 (1.38; 1.76), and 1.35 (1.18; 1.54) among men born in 1955, 1965-1969, 1970
      1979, and 1980-1984. Confounding by familial BMI or IQ could not be controlled.
      CONCLUSIONS: The association between BMI and IQ is subject to secular trends.

PMID- 25865573
TI  - Reply: To PMID 25371111.

PMID- 25865574
TI  - Prostate cancer detection: The impact of obesity on Asian men.
AB  - OBJECTIVE: To evaluate the impact of body mass index (BMI) on prostate cancer
      detection in biopsy-naive men presenting to a single tertiary hospital in
      Singapore. MATERIALS AND METHODS: We retrospectively examined 458 men who
      underwent initial prostate biopsies between January 2012 and April 2014.
      Indications for biopsy were serum prostate-specific antigen level>=4.0ng/ml, or
      digital rectal examination findings suspicious for malignancy, or both. Only men
      with serum prostate-specific antigen level <20ng/ml were included. BMI categories
      were based on the World Health Organization recommendations (normal:<25.0,
      overweight: 25.0-29.9, and obese: >=30). RESULTS: Of the 458 men included in our
      cohort, 125 (27.3%) men were positive for prostate cancer on biopsy, with 69
      (15.1%) being clinically significant (Gleason>=7). Men with BMI>=25kg/m(2)
      (41.7%) were younger (67.2 vs. 68.8y, P = 0.030), had larger prostates (45.5 vs.
      40.1g, P = 0.014), and were more likely to have a positive biopsy finding (34.6%
      vs. 22.1%, P = 0.003). On multivariate analysis, being overweight or obese was
      associated with increased risk of having prostate cancer on biopsy (odds ratio
      [OR] = 2.61, 95% CI: 1.58-4.30, P<0.001 and OR = 3.26, 95% CI: 1.37-7.73 P =
      0.007, respectively). The same trend was observed for clinically significant
      cancers but not for clinically insignificant cancers (OR = 3.57, 95% CI: 1.87
      6.82, P<0.001 and OR = 3.86, 95% CI: 1.33-11.21, P = 0.013 for being overweight
      and obese, respectively). CONCLUSION: Asian men with BMI>=25kg/m(2) are at
      greater risk of having a positive initial biopsy result. The BMI threshold
      (BMI>=25kg/m(2)) for Asian men to be at increased risk of prostate cancer
      detection on initial biopsy is lower than that of Western populations
      (BMI>=30kg/m(2)).

PMID- 25865575
TI  - Profiling aged artisanal Cheddar cheese using secondary electrospray ionization
      mass spectrometry.
AB  - A number of direct injection mass spectrometry methods that can sample foods
      nondestructively and without sample preparation are being developed with
      applications ranging from the rapid assessment of food safety to the verification
      of protected designations of origin. In this pilot study, secondary electrospray
      ionization mass spectrometry (SESI-MS) in positive- and negative-ion modes was
      used to collect volatile fingerprints of artisanal Cheddar cheeses aged for one
      to three years. SESI-MS fingerprints were found to change in an aging-dependent
      manner and can be used to descriptively and predictively categorize Cheddars by
      their aging period, identify volatile components that increase or decrease with
      aging, and robustly discriminate individual batches of artisanal cheese. From
      these results, it was concluded that SESI-MS volatile fingerprinting could be
      used by artisanal food producers to characterize their products during production
      and aging, providing useful data to help them maximize the value of each batch. 

PMID- 25865576
TI  - Distributed capillary adiabatic tissue homogeneity model in parametric multi
      channel blind AIF estimation using DCE-MRI.
AB  - PURPOSE: One of the main challenges in quantitative dynamic contrast-enhanced
      (DCE) MRI is estimation of the arterial input function (AIF). Usually, the signal
      from a single artery (ignoring contrast dispersion, partial volume effects and
      flow artifacts) or a population average of such signals (also ignoring
      variability between patients) is used. METHODS: Multi-channel blind deconvolution
      is an alternative approach avoiding most of these problems. The AIF is estimated
      directly from the measured tracer concentration curves in several tissues. This
      contribution extends the published methods of multi-channel blind deconvolution
      by applying a more realistic model of the impulse residue function, the
      distributed capillary adiabatic tissue homogeneity model (DCATH). In addition, an
      alternative AIF model is used and several AIF-scaling methods are tested.
      RESULTS: The proposed method is evaluated on synthetic data with respect to the
      number of tissue regions and to the signal-to-noise ratio. Evaluation on clinical
      data (renal cell carcinoma patients before and after the beginning of the
      treatment) gave consistent results. An initial evaluation on clinical data
      indicates more reliable and less noise sensitive perfusion parameter estimates.
      CONCLUSION: Blind multi-channel deconvolution using the DCATH model might be a
      method of choice for AIF estimation in a clinical setup.

PMID- 25865578
TI  - Couples' Coping After Stroke-A Pilot Intervention Study.
AB  - PURPOSE: This mixed-methods pilot study examined the impact of a
      psychoeducational intervention (PEI) to expand coping skills and identify themes
      for focused nursing strategies to assist poststroke couples. DESIGN: Outcome
      variables, including dyadic coping, quality of life, depression, and self-care
      self-efficacy, were measured in experimental and control groups initially and
      after PEI was created with experimental couples in six home sessions. METHOD:
      Repeated measures analysis of variance compared control (n = 5 stroke survivors;
      n = 5 spouses) and experimental groups' (n = 5 stroke survivors; n = 5 spouses)
      on outcomes. FINDINGS: Significant increase occurred in experimental group stroke
      survivors in coping by oneself and quality of life; depressive symptoms
      decreased. Significant increase in positive dyadic coping occurred for
      experimental group spouses. PEI intervention generated a major theme.
      CONCLUSIONS: Nurse-initiated cognitive coping intervention was supported by
      experimental group's elements. CLINICAL RELEVANCE: Nurses may use
      psychoeducational techniques to motivate stroke couples.

PMID- 25865579
TI  - Total Synthesis of Ellagitannins through Regioselective Sequential
      Functionalization of Unprotected Glucose.
AB  - Short total syntheses of natural glycosides (ellagitannins) were performed
      through sequential and regioselective functionalization of the hydroxy groups of
      unprotected glucose. The key reactions are beta-selective glycosidation of a
      gallic acid derivative by using unprotected glucose as a glycosyl donor and
      catalyst-controlled regioselective introduction of a galloyl group into the
      inherently less reactive hydroxy group of the glucoside. 

PMID- 25865577
TI  - Multiple levels of epigenetic control for bone biology and pathology.
AB  - Multiple dimensions of epigenetic control contribute to regulation of gene
      expression that governs bone biology and pathology. Once confined to DNA
      methylation and a limited number of post-translational modifications of histone
      proteins, the definition of epigenetic mechanisms is expanding to include
      contributions of non-coding RNAs and mitotic bookmarking, a mechanism for
      retaining phenotype identity during cell proliferation. Together these different
      levels of epigenetic control of physiological processes and their perturbations
      that are associated with compromised gene expression during the onset and
      progression of disease, have contributed to an unprecedented understanding of the
      activities (operation) of the genomic landscape. Here, we address general
      concepts that explain the contribution of epigenetic control to the dynamic
      regulation of gene expression during eukaryotic transcription. This article is
      part of a Special Issue entitled Epigenetics and Bone. 

PMID- 25865580
TI  - Who is too healthy and who is too sick for liver transplantation: external
      validation of prognostic scores and survival-benefit estimation.
AB  - OBJECTIVE: Thresholds for when a patient should be considered too healthy or too
      sick to undergo liver transplantation (LT) have been pursued, but have undergone
      little external validation and may differ between centers and countries. MATERIAL
      AND METHODS: We investigated the ability of the Model for End-stage Liver Disease
      (MELD), D-MELD, Donor Risk Index (DRI) and Balance of Risk (BAR) scores to
      predict 1-year graft survival, and determined the 1-year survival-benefit of LT,
      compared with conservative management, according to MELD score and graft quality
      among 538 adult LT recipients with underlying chronic non-malignant liver
      disease. RESULTS: One-year graft survival rates showed small, but statistically
      significant variation according to MELD (p = 0.002) and D-MELD score (p = 0.04),
      and among LTs after year 2000 also according to BAR score (p = 0.01), but not
      according to DRI. Diagnostic accuracy of these scores was poor; area under the
      curve was 0.50-0.65 depending on the score. A 1-year survival-benefit of LT
      emerged at MELD scores >=15, but also at lower MELD scores when using high
      quality grafts (DRI <1.075). CONCLUSIONS: The performance of various prognostic
      scores in the Finnish setting was poor. Careful clinical evaluation is imperative
      when deciding on the timing of LT in the course of chronic liver disease.

PMID- 25865581
TI  - [Telephone assistance and complications of cardiopulmonary resuscitation].

PMID- 25865582
TI  - [Limitations of transcranial Doppler in the diagnosis of brain death].

PMID- 25865583
TI  - [Weston-Hurst disease in a patient with seizures].

PMID- 25865584
TI  - No causal effect of left hemisphere hyperactivity in the genesis of neglect-like
      behavior.
AB  - Spatial neglect is traditionally explained as an imbalance of the
      interhemispheric reciprocal inhibition exerted by the two hemispheres: after a
      right lesion, the contralesional hemisphere becomes disinhibited and its enhanced
      activity suppresses the activity in the lesioned one. Even though the
      hyperexcitability of the left hemisphere is the theoretical framework of several
      rehabilitation interventions using non-invasive brain stimulation protocols in
      neglect, no study has yet investigated directly the actual state of cortical
      excitability of the contralesional hemisphere immediately after the brain lesion.
      The present study represents the first attempt to directly assess the
      interhemispheric rivalry model adopting a novel approach based on the induction
      of neglect-like biases in healthy participants. Applying repetitive transcranial
      magnetic stimulation (rTMS) over the right posterior parietal cortex while
      concurrently recording the EEG activity allows to measure specific
      neurophysiological markers of cortical activity (i.e. TMS-evoked potentials,
      TEPs) both over the stimulated right hemisphere and over the contralateral
      homologous area. Besides the effectiveness of the protocol used in modulating
      behavior, our results show an inhibition of the cortical excitability of the
      directly stimulated parietal cortex (right hemisphere) and, most importantly, a
      comparable reduction of cortical excitability of the homologous contralateral
      (left) area. TEPs and additional electrophysiological measures reliably provide
      strong evidence for a bilateral hypo-activation following TMS induction of
      neglect-like biases. These results suggest that the parietal imbalance typically
      found in neglect patients could reflect a long-term maladaptive plastic
      reorganization that follows a brain lesion. 

PMID- 25865585
TI  - Genetic research, behavioural science, and child and adolescent mental health in
      South Africa: an important new agenda.
AB  - BACKGROUND: Since the announcement of the results of the international research
      project to unravel the human genome in the early 1990s there has been a
      burgeoning of research into the genetic basis of psychopathology and development.
      South African behavioural researchers, however, have reasons to be cautious about
      the benefits of genetic research in the light of the historical link between
      eugenic interests and practices which were attractive to ideologies such as
      Nazism and apartheid. METHODS: In this article we discuss the burgeoning
      interface internationally between behavioural and genetic research. We describe a
      number of areas of recent research that are particularly relevant to child and
      adolescent mental health in South Africa (antisocial behaviour, disorganised
      attachment and depression) that are beginning to illuminate the interactions
      between the behavioural and genetic domains. DISCUSSION: We argue that we need to
      engage more actively with what the sciences of the brain and behaviour have to
      offer, and in so doing make a case for the urgent inclusion of genetic research
      in mental health research in South Africa.

PMID- 25865586
TI  - Personality disturbance in adolescents living with HIV/AIDS: a review.
AB  - This paper presents a review of theoretical and empirical research on personality
      disturbance in adolescents living with HIV/AIDS. First we discuss the
      relationship between mental health in adolescents and HIV/AIDS, and second we
      provide an overview of personality disturbance in adolescence with particular
      attention given to: (a) the prevalence and presence of personality disturbance in
      adolescents living with HIV/AIDS (b) the effect of personality disturbance on
      compliance on antiretroviral treatment and (c) stress of an HIV diagnosis in
      adolescents with personality disturbance. In conclusion treatment issues and
      recommendations are discussed. 

PMID- 25865587
TI  - Prevalence and factors associated with depression in HIV/AIDS patients aged 15-25
      years at Aminu Kano Teaching Hospital, Nigeria.
AB  - OBJECTIVE: The objective of the study is to determine the prevalence and factors
      associated with depression in HIV/AIDS patients aged 15-25 years in Aminu Kano
      Teaching Hospital, Kano, Nigeria. METHOD: The study is descriptive and cross
      sectional, and was carried out over a period of 16 weeks at Aminu Kano Teaching
      Hospital, Nigeria. The study population included HIV/AIDS patients in the age
      bracket admitted into the hospital's medical wards, and those attending the
      HIV/AIDS clinic. The Hospital Anxiety and Depression Scale (HAD) was administered
      to the respondents to screen for depression. Those who scored 8 and above were
      assessed clinically for depression using the International Classification of
      Disease Version 10 (ICD-10), and their depression classified into mild, moderate
      and severe. The severity of the depression of this group of patients was again
      classified as mild, moderate and severe using the Hamilton Depression Rating
      Scale (HDRS). RESULT: Of the respondents, 39.91% were found to be depressed, with
      stage of the disease, inability to afford medication, unemployment, lack of
      social support, inability to tolerate HAART and other drugs in the management of
      HIV, and CD4 cell (Cluster of Differentiation 4 T-lymphocytes subgroup, the cells
      specifically targeted by HIV) count level found to be associated with depression.
      CONCLUSION: Depression is a highly prevalent disorder in the study subjects.
      Based on these findings, it is recommended that a comprehensive psychiatric
      treatment strategy should be initiated using a biopsychosocial framework that
      includes psychopharmacological and psychotherapeutic intervention to reduce
      morbidity and mortality in affected patients.

PMID- 25865588
TI  - Psychometric properties of the Multidimensional Anxiety Scale for Children (MASC)
      amongst Nairobi public secondary school children, Kenya.
AB  - BACKGROUND: There are few psychometric instruments whose properties have been
      studied in a developing country's context. AIM: To determine the psychometric
      properties of the Multidimensional Anxiety Scale for Children (MASC) in Nairobi
      public secondary school children, Kenya. METHOD: Concurrent self-administration
      of the MASC and Children's Depression Inventory (CDI) to students in Nairobi
      public secondary schools. RESULTS: The MASC had a high overall internal
      consistency alpha co-efficient (0.85) in the Kenyan sample, which is similar to
      Western findings, and is hence a reliable tool for measuring anxiety in the study
      population. It was also similar to the findings from two Western studies in the
      anxiety domains of physical symptoms, social anxiety, separation anxiety and harm
      avoidance. The correlation co-efficient with CDI was similar to Scandinavian
      findings. CONCLUSION: The MASC can be used in Kenyan children and, by extension,
      other Africa children.

PMID- 25865589
TI  - Family functioning and suicidal ideation/behaviour in adolescents: a pilot study.
AB  - OBJECTIVE: The main aim of this study was to explore the associations between
      specific aspects of family functioning and adolescent suicidal
      ideation/behaviour. METHOD: Participants were 87 high school students (43 male
      and 44 female) aged between 14 and 16 years of age. They completed a
      questionnaire measuring various aspects of family functioning and suicidal
      ideation/behaviour. The specific dimensions of family functioning assessed were:
      connection, psychological control and behavioural regulation in the parent
      adolescent relationship, family conflict and family structure. RESULTS: The
      results of t-test and chi-square analyses indicated that adolescents who reported
      suicidal ideation or behaviour in the previous year experienced lower levels of
      connection and regulation and higher levels of conflict and psychological control
      in the parent-child relationship than non-suicidal adolescents. Family structure
      and interparental conflict were not significantly associated with suicidal
      ideation/behaviour. CONCLUSIONS: The quality of relationships between adolescents
      and both of their parents may be important in distinguishing South African
      adolescents with recent suicidal ideation/behaviour from non-suicidal controls.

PMID- 25865591
TI  - Overcoming body image disturbance: a programme for people with eating disorders.

PMID- 25865590
TI  - Psycho-legal issues surrounding the rape of children and adolescents with mental
      retardation.
AB  - The rape of individuals with mental retardation poses challenges for the judicial
      system as well as for the survivors themselves. As a result, the courts tend to
      refer these individuals for forensic mental health examination to assist them in
      proceeding with criminal trials. This sequence of events may appear unusual,
      considering that these individuals have already suffered significant trauma, and
      yet have to undergo mental health evaluation before the trial can begin. The
      questions posed by the courts to mental health experts deal with the cognitive
      assessment of the rape survivor, the survivor's ability to testify, and her/his
      capacity to consent to sexual intercourse. The paper provides an outline of this
      situation within the authors' work context in the KwaZulu-Natal Midlands, and
      also engages in a critical discussion of the issues involved in such forensic
      examinations, taking into consideration the implications for the expert witness
      and her/his approach to such examinations. 

PMID- 25865592
TI  - Children's Anxiety: A Contextual Approach.

PMID- 25865594
TI  - Journal abstracts from current research in the field of child and adolescent
      mental health.

PMID- 25865593
TI  - Paediatric trauma and child abuse.

PMID- 25865595
TI  - Where have all the therapists gone? Children, social responsiveness and justice.

PMID- 25865596
TI  - Strengthening families for the care and protection of children affected by HIV
      and AIDS.

PMID- 25865597
TI  - Reducing the harm of opioid overdose with the safe use of naloxone : a
      pharmacologic review.
AB  - INTRODUCTION: Opioid overdose fatality has increased threefold since 1999. As a
      result, prescription drug overdose surpassed motor vehicle collision as the
      leading cause of unintentional injury-related death in the USA. Naloxone , an
      opioid antagonist that has been available for decades, can safely reverse opioid
      overdose if used promptly and correctly. However, clinicians often overestimate
      the dose of naloxone needed to achieve the desired clinical outcome,
      precipitating acute opioid withdrawal syndrome (OWS). AREAS COVERED: This article
      provides a comprehensive review of naloxone's pharmacologic properties and its
      clinical application to promote the safe use of naloxone in acute management of
      opioid intoxication and to mitigate the risk of precipitated OWS. Available
      clinical data on opioid-receptor kinetics that influence the reversal of opioid
      agonism by naloxone are discussed. Additionally, the legal and social barriers to
      take home naloxone programs are addressed. EXPERT OPINION: Naloxone is an
      intrinsically safe drug, and may be administered in large doses with minimal
      clinical effect in non-opioid-dependent patients. However, when administered to
      opioid-dependent patients, naloxone can result in acute opioid withdrawal.
      Therefore, it is prudent to use low-dose naloxone (0.04 mg) with appropriate
      titration to reverse ventilatory depression in this population.

PMID- 25865598
TI  - MRI interactions of a fully implantable pressure monitoring device.
AB  - PURPOSE: To investigate the potential patient risk and interactions between a
      prototype implantable pressure monitoring device and a 3T clinical magnetic
      resonance imaging (MRI) machine to guide device design towards MR Conditional
      safety approval. MATERIALS AND METHODS: The pressure monitor device contained a
      catheter-mounted piezo-resistive pressure sensor, rechargeable battery, wireless
      communication system, and inductive pickup coil. Standard testing methods were
      used to guide experiments to investigate static field induced force and torque,
      radiofrequency (RF)-induced heating, image artifacts, and the MR's effect on
      device function. The specific clinical application of intracranial pressure
      monitoring was considered. RF-induced heating experiments were supported by
      numerical modeling of the RF body coil, the device, and experimental phantom.
      RESULTS: Sensing catheter lead length and configuration was an important
      component of the device design. A short 150 mm length catheter produced a heating
      effect of less than 2 degrees C and a long 420 mm length catheter caused heating
      of 7.2 degrees C. Static magnetic field interactions were below standard safety
      risk levels and the MR did not interfere with device function; however, artifacts
      have the potential to interfere with image quality. CONCLUSION: Investigation of
      MR interactions at the prototype stage provides useful implantable device design
      guidance and confidence that an implantable pressure monitor may be able to
      achieve MR Conditional safety approval.

PMID- 25865599
TI  - Bioinspired nanoreactors for the biomineralisation of metallic-based
      nanoparticles for nanomedicine.
AB  - This review explores the synthesis of inorganic metallic-based nanoparticles
      (MBNPs) (metals, alloys, metal oxides) using biological and biologically inspired
      nanoreactors for precipitation/crystallisation. Such nanoparticles exhibit a
      range of nanoscale properties such as surface plasmon resonance (nobel metals
      e.g. Au), fluorescence (semiconductor quantum dots e.g. CdSe) and nanomagnetism
      (magnetic alloys e.g. CoPt and iron oxides e.g. magnetite), which are currently
      the subject of intensive research for their applicability in diagnostic and
      therapeutic nanomedicine. For such applications, MBNPs are required to be
      biocompatible, of a precise size and shape for a consistent signal or output and
      be easily modified with biomolecules for applications. Ideally the MBNPs would be
      obtained via an environmentally-friendly synthetic route. A biological or
      biologically inspired nanoreactor synthesis of MBNPs is shown to address these
      issues. Biological nanoreactors for crystallizing MBNPs within cells
      (magnetosomes), protein cages (ferritin) and virus capsids (cowpea chlorotic
      mottle, cowpea mosaic and tobacco mosaic viruses), are discussed along with how
      these have been modified for applications and for the next generation of new
      materials. Biomimetic liposome, polymersome and even designed self-assembled
      proteinosome nanoreactors are also reviewed for MBNP crystallisation and further
      modification for applications. With the advent of synthetic biology, the research
      and understanding in this field is growing, with the goal of realising
      nanoreactor synthesis of MBNPs for biomedical applications within our grasp in
      the near future. 

PMID- 25865600
TI  - Normalized activation in the somatosensory cortex 30 years following nerve repair
      in children: an fMRI study.
AB  - The clinical outcome following a peripheral nerve injury in the upper extremity
      is generally better in young children than in teenagers and in adults, but the
      mechanism behind this difference is unknown. In 28 patients with a complete
      median nerve injury sustained at the ages of 1-13 years (n = 13) and 14-20 years
      (n = 15), the cortical activation during tactile finger stimulation of the
      injured and healthy hands was monitored at a median time since injury of 28 years
      using functional magnetic resonance imaging (fMRI) at 3 Tesla. The results from
      the fMRI were compared with the clinical outcome and electroneurography. The
      cortical activation pattern following sensory stimulation of the median nerve
      innervated fingers was dependent on the patient's age at injury. Those injured at
      a young age (1-13 years) had an activation pattern similar to that of healthy
      controls. Furthermore, they showed a clinical outcome significantly superior (P =
      0.001) to the outcome in subjects injured at a later age; however,
      electroneurographical parameters did not differ between the groups. In subjects
      injured at age 14-20 years, a more extended activation of the contralateral
      hemisphere was seen in general. Interestingly, these patients also displayed
      changes in the ipsilateral hemisphere where a reduced inhibition of somatosensory
      areas was seen. This loss of ipsilateral inhibition correlated to increasing age
      at injury as well as to poor recovery of sensory functions in the hand. In
      conclusion, cerebral changes in both brain hemispheres may explain differences in
      clinical outcome following a median nerve injury in childhood or adolescence.

PMID- 25865601
TI  - Identification of functionally methylated regions based on discriminant analysis
      through integrating methylation and gene expression data.
AB  - DNA methylation is essential not only in cellular differentiation but also in
      diseases. Identification of differentially methylated patterns between case and
      control groups is important in understanding the mechanism and possible
      functionality of complex diseases. We propose a method to find possible
      functionally methylated regions which not only are differentially methylated but
      also have an effect on gene expression. It integrates methylation and gene
      expression data and is based on distance discriminant analysis (DDA). In the
      procedure of identifying differentially methylated regions (DMRs), we do not need
      to cluster methylation sites or partition the genome in advance. Therefore, the
      identified DMRs have a larger coverage than those of bump hunting and Ong's
      methods. Furthermore, through incorporating gene expression data as a
      complementary source, whether these DMRs are functional is determined through
      estimating the difference of the corresponding genes. Through a comparison of our
      approach with bump hunting and Ong's methods for simulation data, it is shown
      that our method is more powerful in identifying DMRs which have a larger distance
      in the genome, or only consist of a few sites and have higher sensitivity and
      specificity. Also, our method is more robust to heterogeneity of data. Applied to
      different real datasets, we find that most of the functional DMRs are hyper
      methylated and located at CpG rich regions (e.g. islands, TSS200 and TSS1500),
      consistent with the fact that the methylation levels of CpG islands are higher in
      tumors than normal. Through comparing and analyzing the results of different
      datasets, we find that the change of methylation in some regions may be related
      to diseases through changing expression of the corresponding genes, and show the
      effectiveness of our method. 

PMID- 25865603
TI  - Pain and Physical Functioning in Neuropathic Pain: A Systematic Review of
      Psychometric Properties of Various Outcome Measures.
AB  - INTRODUCTION: A range of outcome measures across various domains are used to
      evaluate change following an intervention in clinical trials on chronic
      neuropathic pain (NeP). However, to capture a real change in the variable of
      interest, the psychometric properties of a particular measure should demonstrate
      appropriate methodological quality. Various outcome measures in the domains of
      pain and physical functioning have been used in the literature for NeP, for which
      individual properties (eg, reliability/validity) have been reported. To date,
      there is no definitive synthesis of evidence on the psychometric properties of
      those outcome measures; thus, the aim of this systematic review was to evaluate
      the methodological quality [COnsensus-based Standards for the selection of health
      status Measurement INstruments (COSMIN) guidelines] of studies that evaluated
      psychometric properties of pain and physical functioning outcome measures used
      for NeP. METHODS: Specific MeSH/keywords related to 3 areas (pain and/or physical
      functioning, psychometric properties, and NeP) were used to retrieve relevant
      studies (English language) in key electronic databases (MEDLINE (Ovid), CINAHL
      (EBSCO), Scopus, AMED, and Web of Science) from database inception-July 2012.
      Articles retrieval/screening and quality analysis (COSMIN) were carried out by 2
      independent reviewers. RESULTS: Twenty-four pain and thirty-seven physical
      functioning outcome measures were identified, varying in methodological quality
      from poor-excellent. CONCLUSION: Although a variety of pain and physical
      functioning outcome measures have been reported in the literature, few have
      demonstrate methodologically strong psychometric properties. Thus, future
      research is required to further investigate the psychometric properties of
      existing pain and physical functioning outcome measures used for clinical and
      research purposes.

PMID- 25865602
TI  - Cost-effectiveness of pretransplant sofosbuvir for preventing recurrent hepatitis
      C virus infection after liver transplantation.
AB  - There are reports of pretransplant sofosbuvir (SOF) plus ribavirin being
      effective in preventing recurrent hepatitis C virus (HCV) infection after liver
      transplantation (LT). The aim of this study was to assess the cost-effectiveness
      of this strategy in the area served by the North Italy Transplant program. We
      retrospectively assessed the impact of HCV infection on post-LT survival in 2376
      consecutive adult patients (MELD <= 25, unknown genotype, period 2004-2009) and
      the prevalence costs of conventional standard of care (SOC) antiviral therapy
      (pegylated interferon plus ribavirin) after LT. A Markov model was developed to
      compare two strategies: 12-24 weeks of SOF+ ribavirin for pre-LT anti-HCV
      treatment versus on-demand post-LT SOC antiviral therapy. Among the 1794 patients
      undergoing LT, 860 (48%) were HCV+ and 50% of them were given SOC therapy after
      LT (mean cost of drugs and adverse effect management = 14,421? per patient). HCV
      etiology had a strong impact on post-LT survival (hazard ratio = 1.59, 95% CI =
      1.22-2.09, P = 0.0007). After Monte Carlo simulation, pre-LT SOF therapy showed a
      median survival benefit of 1.5 quality-adjusted life years and an Incremental
      cost-effectiveness ratio (ICER) of 30,663?/QALY, proving cost-effective in our
      particular Italian scenario. The costs of SOF therapy, sustained viral response
      rate 12 weeks after LT, and recipient's age were the main ICER predictors at
      multivariate analysis. This study proposes a dynamic model based on real-life
      data from northern Italy for adjusting the costs of pre-LT direct-acting
      antiviral therapies to the actual sustained virological response reached after
      LT.

PMID- 25865604
TI  - Optimum design of a nanoscale spin-Seebeck power device.
AB  - A theoretical model of a nanoscale spin-Seebeck power device (SSPD) is proposed
      based on the longitudinal spin-Seebeck effect in bilayers made of a ferromagnetic
      insulator and a normal metal. Expressions for the power output and thermal
      efficiency of the SSPD are derived analytically. The performance characteristics
      of the nanoscale SSPD are analyzed using numerical simulation. The maximum power
      output density and efficiency are calculated numerically. The effect of the spin
      Hall angle on the performance characteristics of the SSPD is analyzed. The choice
      of materials and the structure of the device are discussed. The optimum criteria
      of some key parameters of the SSPD, such as the power output density, efficiency,
      thickness of the normal metal, and the load resistance, are given. The results
      obtained here could provide a theoretical basis for the optimal design and
      operation of nanoscale SSPDs. 

PMID- 25865605
TI  - DNA damage protection against free radicals of two antioxidant neolignan
      glucosides from sugarcane molasses.
AB  - BACKGROUND: Sugarcane molasses is a potential by-product of the sugarcane
      manufacturing industry that is rich in antioxidant materials. The present study
      aimed to obtain antioxidative compounds from sugarcane molasses and to evaluate
      their ability to protect DNA from oxidative damage. RESULTS: Two neolignan
      glucosides were isolated from sugarcane molasses using bioassay and UV spectra
      monitoring-guided fractionation. The compounds were elucidated as (7R,8S)
      dehydrodiconiferyl alcohol-4-O-beta-d-glucoside (1) and (7S,8R)-simulanol-9'-O
      beta-d-glucoside (2). Neolignan glucoside 2 protected against DNA damage caused
      by free radicals more effectively than did neolignan glucoside 1 (13.62 and 9.08
      umol L(-1) for peroxyl and hydroxyl radicals, respectively, compared to 48.07 and
      14.42 umol L(-1) ). Additionally, neolignan glucoside 2 exhibited superior DNA
      protection against free radicals compared with various known antioxidative
      compounds, including p-coumaric acid, ferulic acid, vanillic acid and
      epigallocatechin gallate. CONCLUSION: The isolated neolignan glucosides from
      sugarcane molasses are able to protect DNA from oxidative damage caused by free
      radicals. This is the first identification of these two compounds in sugarcane
      molasses. The sugarcane molasses can therefore be used as potential nutraceutical
      preventative agents, and the findings may foster the utilization of this by
      product as a bioresource-based product. (c) 2015 Society of Chemical Industry.

PMID- 25865606
TI  - Fowler's syndrome of urinary retention: A retrospective study of co-morbidity.
AB  - AIMS: To study the frequency of pain, psychological, or functional disorders in
      patients with Fowler's syndrome. METHODS: We carried out a retrospective chart
      review of patients with a diagnosis of Fowler's syndrome attending the Uro
      Neurology centre at the National Hospital for Neurology and Neurosurgery between
      2009 and 2013 looking at triggering events, physical and psychological
      comorbidities. RESULTS: Of 62 patients with clinical and electromyographic
      diagnosis of Fowler's syndrome, 31 (50%) had unexplained chronic pain syndromes,
      12 (19%) of these were taking opiates. Fifteen (24%) had "functional"
      neurological symptoms. Abdominopelvic surgery with general anesthesia was the
      leading trigger (n = 21, 35%). CONCLUSIONS: We found high levels of co-morbidity
      with patients having some form of pain (50%), a probable functional disorder
      (24%), or psychological symptoms (31%). There are several potential explanations
      for this association including the effect of developing an apparently unexplained
      distressing condition, confounding effect of opiate use or referral bias. The
      findings suggest a need for prospective systematic study of comorbidity for this
      disabling condition. Neurourol. Urodynam. 35:601-603, 2016. (c) 2015 Wiley
      Periodicals, Inc.

PMID- 25865607
TI  - [Physical activity in leisure time in the prevention of peripheral artery
      disease].

PMID- 25865608
TI  - [Long-lasting multiple cutaneous tumors].

PMID- 25865609
TI  - [Pseudopseudohypoparathyroidism vs progressive osseous heteroplasia in absence of
      family history].

PMID- 25865610
TI  - [Association with IgG3 deficiency in chronic autoimmune neutropenia in adults:
      case report and literatura review].

PMID- 25865611
TI  - [Fatal outcome of immune reconstitution inflammatory sindrome in a patient with
      AIDS-associated Kaposi sarcoma].

PMID- 25865612
TI  - [Tracheobronchial amyloidosis: Diagnosis, treatment and evolution in 5 patients].

PMID- 25865613
TI  - [Cutaneous CD8+ T-cell lymphoma. Regression after HIV antiviral triple therapy].

PMID- 25865614
TI  - Ultrahigh near infrared photoresponsive organic field-effect transistors with
      lead phthalocyanine/C60 heterojunction on poly(vinyl alcohol) gate dielectric.
AB  - Performances of photoresponsive organic field-effect transistors (photOFETs)
      operating in the near infrared (NIR) region utilizing SiO2 as the gate dielectric
      is generally low due to low carrier mobility of the channel. We report on NIR
      photOFETs based on lead phthalocyanine (PbPc)/C60 heterojunction with ultrahigh
      photoresponsivity by utilizing poly(vinyl alcohol) (PVA) as the gate dielectric.
      For 808 nm NIR illumination of 1.69 mW cm(-2), an ultrahigh photoresponsivity of
      21 A W(-1), and an external quantum efficiency of 3230% were obtained at a gate
      voltage of 30 V and a drain voltage of 80 V, which are 124 times and 126 times as
      large as the reference device with SiO2 as the gate dielectric, respectively. The
      ultrahigh enhancement of photoresponsivity is resulted from the huge increase of
      electron mobility of C60 film grown on PVA dielectric. AFM investigations
      revealed that the C60 film grown on PVA is much smooth and uniform and the grain
      size is much larger than that grown on SiO2 dielectric, which together results in
      four orders of magnitude increase of the field-effect electron mobility of C60
      film. 

PMID- 25865615
TI  - Photoprotective effect of botanicals and vitamins: A systematic review of
      clinical trials.
AB  - BACKGROUND: Overexposure to solar radiation is a major contributor to skin cancer
      development and premature skin aging. Botanical extracts and vitamins may
      represent novel photoprotective agents. OBJECTIVE: We sought to systemically
      review clinical evidence for the use of botanically derived agents and vitamins
      as photoprotective agents. METHODS: We systematically searched Embase and PubMed
      databases. Two independent reviewers reviewed abstracts for inclusion. Additional
      relevant studies were identified by a manual review of reference lists. Data from
      eligible studies were extracted independently and discrepancies were resolved by
      consensus. RESULTS: A total of 51 studies met inclusion criteria. Limited
      available evidence indicates that several botanical agents and vitamins in
      topical or oral forms may have promising photoprotective effects. However,
      generalizability of results is limited by small sample sizes. CONCLUSION AND
      RELEVANCE: Botanical extracts and vitamins may add to the armamentarium of sun
      protective agents. Additional high-quality trials are needed to strengthen
      support for their use.

PMID- 25865616
TI  - A lower reduction in umbilical artery pulsatility in mid-pregnancy predicts
      higher infant blood pressure six months after birth.
AB  - AIM: The Norwegian-based Cardiovascular Risk Reduction Diet in Pregnancy study
      found that a cholesterol-lowering diet during pregnancy was associated with an
      accentuated reduction in the umbilical artery pulsatility index. This follow-up
      study assessed the possible association between the index and the infants' blood
      pressure at six months of age. METHODS: In the original study, pregnant women
      consumed an anti-atherogenic or usual diet from gestational weeks 17-20 to birth
      and underwent Doppler velocimetry at 24, 30 and 36 gestational weeks. In this
      follow-up study, blood pressure was measured in 105 mother-infant pairs in the
      intervention group and 106 mother-infant pairs in the control group six months
      after birth. RESULTS: Mean systolic and diastolic blood pressures were not
      significantly different between both groups. When the groups were combined,
      multivariate linear analyses showed that a lower versus higher reduction (>=-0.17
      versus <-0.17) in the umbilical artery pulsatility index between gestational
      weeks 24 and 30 and maternal diastolic blood pressure at six months postpartum
      were significant predictors of higher infant systolic blood pressure (p = 0.03,
      0.01, respectively). CONCLUSION: A lower reduction in umbilical pulsatility index
      in mid-pregnancy was associated with higher infant blood pressure at six months
      of age. This suggests that fetoplacental intrauterine factors may influence
      future cardiovascular risk.

PMID- 25865617
TI  - Transcript abundance, glutathione and apoptosis levels differ between porcine
      oocytes collected from prepubertal and cyclic gilts.
AB  - It is well known that puberty has a strong impact on oocyte developmental
      competence in vitro; however, the reason for this phenomenon at the cellular
      level has not been clarified yet. It is hypothesized that cytoplasmic maturation
      is responsible for oocyte quality and may be impaired in prepubertal gilts.
      Previous results on mitochondrial DNA copy number and mitochondria and cortical
      granule distribution showed that cytoplasmic maturation is a complex trait and
      should include multithreaded analysis. Therefore, the aim of the present research
      was to analyze the transcript abundance of developmentally important genes
      (BMP15, GDF9, GSTA2, ATP5A1, EEF1A1, BAX, BCL2) followed by investigation of the
      glutathione and apoptosis level in oocytes of prepubertal and cyclic gilts. We
      found differences in relative transcript abundance of BMP15 and GDF9 genes after
      IVM, whereas different concentrations of glutathione were noted before IVM (5.3
      vs. 2.9 pmol, respectively). The glutathione level was equalized after IVM (10.3
      vs. 9.1 pmol), whereas the incidence of apoptosis remained similar before (3.9%
      vs. 1.1%) and after IVM (4.5% vs. 1.9%) being higher in prepubertal oocytes. A
      potential impact of gilt puberty on oocyte quality has been therefore masked by
      the significant effect of IVM. Because the maternal effect genes, BMP15 and GDF9,
      play key roles in regulation of folliculogenesis and oocyte-cumulus interaction,
      their upregulation in oocytes of cyclic gilts may result in increased
      developmental competence. On the basis of findings from this and our previous
      research, we suggest that the reduced quality of oocytes from prepubertal females
      is a complex phenomenon and is not related to a single marker trait.

PMID- 25865618
TI  - Prognostic value of copeptin in patients with acute stroke.
AB  - CONTEXT: There is a need to improve stroke care through the prompt identification
      of stroke patients at increased risk of an adverse outcome. OBJECTIVE: To
      evaluate the prognostic value of copeptin in patients with stroke. METHODS: We
      systematically searched PubMed and Embase for relevant studies. Poor outcome and
      mortality were analyzed. RESULTS: Twelve studies, containing 2682 patients, were
      included. Pooled analysis showed that copeptin is an independent prognostic
      marker of poor outcome after acute stroke and there is a borderline effect of
      copeptin in predicting mortality after acute stroke. CONCLUSIONS: Copeptin is an
      independent predictor of poor outcome and mortality for patients with acute
      stroke.

PMID- 25865619
TI  - Correlation between sperm DNA fragmentation index and CMA3 positive spermatozoa
      in globozoospermic patients.
AB  - The absence of the acrosome causes the situation which is called globozoospermia.
      There are a few studies, mostly as case reports, about correlation between levels
      of sperm DNA damage in patients with total round-headed spermatozoa. We
      investigated this correlation as well as CMA3 positive spermatozoa in 20
      globozoospermic men (with more than 90% round-headed spermatozoa) attending to
      Royan Institute. Semen samples divided into three parts to semen analysis, to
      measure DNA fragmentation index (DFI) using sperm chromatin structure assay
      (SCSA) and to detect CMA3(+) sperm cells by chromomycin A3 staining and
      fluorescent microscopy. Our results showed that there were significant
      differences in sperm concentration, total sperm motility, and normal morphology
      between patients and controls group (p < 0.001). Moreover, the average of DFI and
      CMA3 positive spermatozoa in patients group significantly increases compared with
      control group (p < 0.001). A significant correlation between DFI and CMA3(+) in
      total population was also detected in patients group (r = 0.45, p = 0.046). To
      our knowledge, this is the largest study about correlation between DNA damage
      levels and CMA3 positive spermatozoa with round head sperm cells in total
      globozoospermic men. It seems that the increase in DNA damage may be because of
      defective sperm DNA compaction, as we detected CMA3 positive sperm cells in these
      patients.

PMID- 25865620
TI  - Titrating clozapine amidst recommendations proposing high myocarditis risk and
      rapid titrations.

PMID- 25865621
TI  - G-CSF supports long-term muscle regeneration in mouse models of muscular
      dystrophy.
AB  - Duchenne muscular dystrophy (DMD) is a chronic and life-threatening disease that
      is initially supported by muscle regeneration but eventually shows satellite cell
      exhaustion and muscular dysfunction. The life-long maintenance of skeletal muscle
      homoeostasis requires the satellite stem cell pool to be preserved. Asymmetric
      cell division plays a pivotal role in the maintenance of the satellite cell pool.
      Here we show that granulocyte colony-stimulating factor receptor (G-CSFR) is
      asymmetrically expressed in activated satellite cells. G-CSF positively affects
      the satellite cell population during multiple stages of differentiation in ex
      vivo cultured fibres. G-CSF could be important in developing an effective therapy
      for DMD based on its potential to modulate the supply of multiple stages of
      regenerated myocytes. This study shows that the G-CSF-G-CSFR axis is
      fundamentally important for long-term muscle regeneration, functional maintenance
      and lifespan extension in mouse models of DMD with varying severities. 

PMID- 25865622
TI  - Dietary patterns, cardiometabolic risk factors, and the incidence of
      cardiovascular disease in severe obesity.
AB  - OBJECTIVE: The longitudinal associations between a dietary pattern (DP) and
      cardiometabolic risk factors and cardiovascular disease (CVD) incidence were
      investigated in a cohort of adults with severe obesity. METHODS: The analysis
      included 2,037 individuals with severe obesity (>34 and >38 kg/m(2) for men and
      women, respectively) from the Swedish Obese Subjects study repeatedly followed up
      for 10 years. Reduced rank regression was used to identify a DP characterized by
      dietary energy density, saturated fat intake, and fiber density. Mixed models
      examined relationships between repeated measures of DP z-scores and
      cardiometabolic risk factors. Cox proportional hazards models assessed
      relationships between DP scores and CVD incidence. RESULTS: An energy-dense, high
      saturated-fat, and low-fiber DP was derived. A one-unit increase in the DP z
      score between follow-ups was associated with an increase in weight [beta (SE)]
      (1.71 +/- 0.10 kg), waist circumference (1.49 +/- 0.07 cm), BMI (0.60 +/- 0.34
      kg/m2), serum cholesterol (0.06 +/- 0.01 mmol/l), and serum insulin (1.22 +/-
      0.17 mmol/l; all P < 0.0001), as well as in serum triglycerides (0.05 +/- 0.02
      mmol/l; P < 0.05), systolic blood pressure (1.05 +/- 0.27 mmHg; P < 0.001), and
      diastolic blood pressure (0.55 +/- 0.16 mmHg; P < 0.05). No significant
      association was observed between repeated measures of the DP z-scores and CVD
      incidence (HR = 0.96; 95% CI = 0.83-1.12). CONCLUSIONS: An energy-dense, high
      saturated-fat, and low-fiber DP was longitudinally associated with increases in
      cardiometabolic risk factors in severe obesity but not with CVD incidence.

PMID- 25865623
TI  - Sharp switches between regular and swinger mitochondrial replication: 16S rDNA
      systematically exchanging nucleotides A<->T+C<->G in the mitogenome of Kamimuria
      wangi.
AB  - Swinger DNAs are sequences whose homology with known sequences is detected only
      by assuming systematic exchanges between nucleotides. Nine symmetric (X<->Y, i.e.
      A<->C) and fourteen asymmetric (X->Y->Z, i.e. A->C->G) exchanges exist. All
      swinger DNA previously detected in GenBank follow the A<->T+C<->G exchange, while
      mitochondrial swinger RNAs distribute among different swinger types. Here
      different alignment criteria detect 87 additional swinger mitochondrial DNAs (86
      from insects), including the first swinger gene embedded within a complete
      genome, corresponding to the mitochondrial 16S rDNA of the stonefly Kamimuria
      wangi. Other Kamimuria mt genome regions are "regular", stressing unanswered
      questions on (a) swinger polymerization regulation; (b) swinger 16S rDNA
      functions; and (c) specificity to rDNA, in particular 16S rDNA. Sharp switches
      between regular and swinger replication, together with previous observations on
      swinger transcription, suggest that swinger replication might be due to a switch
      in polymerization mode of regular polymerases and the possibility of swinger
      encoded information, predicted in primordial genes such as rDNA.

PMID- 25865624
TI  - Differentially expressed MicroRNAs provide mechanistic insight into fibrosis
      associated liver carcinogenesis in mice.
AB  - Hepatocellular carcinoma (HCC) is one of the most prevalent human cancers, with a
      rising incidence worldwide. The molecular mechanisms associated with the
      development of HCC are complex and include multiple interconnected molecular
      alterations with mounting evidence indicating an important role of microRNAs
      (miRNAs) in the pathogenesis of HCC. In humans, the development of HCC is
      commonly associated with liver cirrhosis. To study fibrosis-associated liver
      carcinogenesis, we used a mouse model designed to emulate the development of HCC
      in cirrhotic liver. Specifically, we were interested in evaluating the role of
      miRNAs in the molecular pathogenesis of liver carcinogenesis in male B6C3F1/J
      mice treated with N-nitrosodiethylamine (DEN) or carbon tetrachloride (CCl4 )
      alone or a combination of DEN and CCl4 and characterized by a differential tumor
      incidence that increased in the following order: DEN<CCl4 <DEN+CCl4 . Treatment
      with DEN alone had negligible effect on hepatic miRNA expression. In contrast,
      treatment with either CCl4 alone or a combination of DEN and CCl4 resulted in
      major changes in miRNA expression. The analysis of miRNA profiles demonstrated an
      involvement of dysregulated miRNAs in major processes associated with the
      development of liver tumors, including inflammation, fibrosis, and stem cell
      activation. Importantly, the greatest incidence of liver tumors in mice treated
      with DEN+CCl4 was accompanied by a distinct over-expression of miRNAs suggesting
      that miRNA alterations may be responsible, at least in part, for the high tumor
      incidence.

PMID- 25865625
TI  - Fishpathogens.eu/noda: a free and handy online platform for Betanodavirus
      targeted research and data sharing.
AB  - Viral nervous necrosis (VNN) is a severe neuropathological disease affecting a
      broad variety of finfish species worldwide. The causative agents of VNN are small
      viruses with a bi-segmented RNA genome known as betanodaviruses. At least four
      species with distinct but yet insufficiently characterized epidemiological
      features are recognized. The spread of VNN to an increasing number of host
      species, its wide geographic extent and its economical and ecological impacts
      justify the importance of collating as much molecular data as possible for
      tracing the origin of viral isolates and highlight the need for a freely
      accessible tool for epidemiological and molecular data sharing and consultation.
      For this purpose, we established a web-based specific database using the
      www.fishpathogens.eu platform, with the aim of collecting molecular and
      epidemiological information on VNN viruses, with relevance to their control,
      management and research studies. 

PMID- 25865626
TI  - Atherosclerosis - A matter of unresolved inflammation.
AB  - Atherosclerosis is commonly looked upon as a chronic inflammatory disease of the
      arterial wall arising from an unbalanced lipid metabolism and a maladaptive
      inflammatory response. However, atherosclerosis is not merely an inflammation of
      the vessel wall. In fact, the cardinal signs of unstable atherosclerotic lesions
      are primarily characteristics of failed resolution of a chronic inflammation. In
      contrast to acute inflammatory events which are typically self-limiting,
      atherosclerosis is an unresolved inflammatory condition, lacking the switch from
      the pro-inflammatory to the pro-resolving phase, the latter characterized by
      termination of inflammatory cell recruitment, removal of inflammatory cells from
      the site of inflammation by apoptosis and dead cell clearance, reprogramming of
      macrophages toward an anti-inflammatory, regenerative phenotype, and finally
      egress of effector cells and tissue regeneration. Here we present an overview on
      mechanisms of failed resolution contributing to atheroprogression and deliver a
      summary of novel therapeutic strategies to restore resolution in inflamed
      arteries. 

PMID- 25865627
TI  - A microsatellite-based linkage map for song sparrows (Melospiza melodia).
AB  - Although linkage maps are important tools in evolutionary biology, their
      availability for wild populations is limited. The population of song sparrows
      (Melospiza melodia) on Mandarte Island, Canada, is among the more intensively
      studied wild animal populations. Its long-term pedigree data, together with
      extensive genetic sampling, have allowed the study of a range of questions in
      evolutionary biology and ecology. However, the availability of genetic markers
      has been limited. We here describe 191 new microsatellite loci, including 160
      high-quality polymorphic autosomal, 7 Z-linked and 1 W-linked markers. We used
      these markers to construct a linkage map for song sparrows with a total sex
      averaged map length of 1731 cM and covering 35 linkage groups, and hence, these
      markers cover most of the 38-40 chromosomes. Female and male map lengths did not
      differ significantly. We then bioinformatically mapped these loci to the zebra
      finch (Taeniopygia guttata) genome and found that linkage groups were conserved
      between song sparrows and zebra finches. Compared to the zebra finch, marker
      order within small linkage groups was well conserved, whereas the larger linkage
      groups showed some intrachromosomal rearrangements. Finally, we show that as
      expected, recombination frequency between linked loci explained the majority of
      variation in gametic phase disequilibrium. Yet, there was substantial overlap in
      gametic phase disequilibrium between pairs of linked and unlinked loci. Given
      that the microsatellites described here lie on 35 of the 38-40 chromosomes, these
      markers will be useful for studies in this species, as well as for comparative
      genomics studies with other species.

PMID- 25865628
TI  - Measurement Error in Public Health Insurance Reporting in the American Community
      Survey: Evidence from Record Linkage.
AB  - OBJECTIVE: Examine measurement error to public health insurance in the American
      Community Survey (ACS). DATA SOURCES/STUDY SETTING: The ACS and the Medicaid
      Statistical Information System (MSIS). STUDY DESIGN: We tabulated the two data
      sources separately and then merged the data and examined health insurance reports
      among ACS cases known to be enrolled in Medicaid or expansion Children's Health
      Insurance Program (CHIP) benefits. DATA COLLECTION/EXTRACTION METHODS: The two
      data sources were merged using protected identification keys. ACS respondents
      were considered enrolled if they had full benefit Medicaid or expansion CHIP
      coverage on the date of interview. PRINCIPAL FINDINGS: On an aggregated basis,
      the ACS overcounts the MSIS. After merging the data, we estimate a false-negative
      rate in the 2009 ACS of 21.6 percent. The false-negative rate varies across
      states, demographic groups, and year. Of known Medicaid and expansion CHIP
      enrollees, 12.5 percent were coded to some other coverage and 9.1 percent were
      coded as uninsured. CONCLUSIONS: The false-negative rate in the ACS is on par
      with other federal surveys. However, unlike other surveys, the ACS overcounts the
      MSIS on an aggregated basis. Future work is needed to disentangle the causes of
      the ACS overcount.

PMID- 25865629
TI  - Interfacial properties of asphaltenes at toluene-water interfaces.
AB  - Asphaltenes are "n-alkane insoluble" species in crude oil that stabilize water-in
      oil emulsions. To understand asphaltene adsorption mechanisms at oil-water
      interfaces and coalescence blockage, we first studied the behavior in aliphatic
      oil-water systems in which asphaltenes are almost insoluble. They adsorbed as
      monomers, giving a unique master curve relating interfacial tension (IFT) to
      interfacial coverage through a Langmuir equation of state (EoS). The long-time
      surface coverage was independent of asphaltene bulk concentration and
      asymptotically approached the 2-D packing limit for polydisperse disks. On
      coalescence, the surface coverage exceeded the 2-D limit and the asphaltene film
      appeared to become solidlike, apparently undergoing a transition to a soft glassy
      material and blocking further coalescence. However, real systems consist of
      mixtures of aliphatic and aromatic components in which asphaltenes may be quite
      soluble. To understand solubility effects, we focus here on how the increased
      bulk solubility of asphaltenes affects their interfacial properties in comparison
      to aliphatic oil-water systems. Unlike the "almost irreversible" adsorption of
      asphaltenes where the asymptotic interfacial coverage was independent of the bulk
      concentration, an equilibrium surface pressure, dependent on bulk concentration,
      was obtained for toluene-water systems because of adsorption being balanced by
      desorption. The equilibrium surface coverage could be obtained from the short-
      and long-term Ward-Tordai approximations. The behavior of the equilibrium surface
      pressure with the equilibrium surface coverage was then derived. These data for
      various asphaltene concentrations were used to determine the EoS, which for
      toluene-water could also be fitted by the Langmuir EoS with Gammainfinity = 3.3
      molecule/nm(2), the same value as that found for these asphaltenes in aliphatic
      media. Asphaltene solubility in the bulk phase only appears to affect the
      adsorption isotherm but not the EoS. Further support for these observations is
      provided by dilatational rheology experiments for the EoS and contraction
      experiments in which desorption to the equilibrium surface pressure was observed.

PMID- 25865630
TI  - Co-expression of NCED and ALO improves vitamin C level and tolerance to drought
      and chilling in transgenic tobacco and stylo plants.
AB  - Abscisic acid (ABA) regulates plant adaptive responses to various environmental
      stresses, while L-ascorbic acid (AsA) that is also named vitamin C is an
      important antioxidant and involves in plant stress tolerance and the immune
      system in domestic animals. Transgenic tobacco (Nicotiana tabacum L.) and stylo
      [Stylosanthes guianensis (Aublet) Swartz], a forage legume, plants co-expressing
      stylo 9-cis-epoxycarotenoid dioxygenase (SgNCED1) and yeast D-arabinono-1,4
      lactone oxidase (ALO) genes were generated in this study, and tolerance to
      drought and chilling was analysed in comparison with transgenic tobacco
      overexpressing SgNCED1 or ALO and the wild-type plants. Compared to the SgNCED1
      or ALO transgenic plants, in which only ABA or AsA levels were increased, both
      ABA and AsA levels were increased in transgenic tobacco and stylo plants co
      expressing SgNCED1 and ALO genes. Compared to the wild type, an enhanced drought
      tolerance was observed in SgNCED1 transgenic tobacco plants with induced
      expression of drought-responsive genes, but not in ALO plants, while an enhanced
      chilling tolerance was observed in ALO transgenic tobaccos with induced
      expression of cold-responsive genes, but not in SgNCED1 plants. Co-expression of
      SgNCED1 and ALO genes resulted in elevated tolerance to both drought and chilling
      in transgenic tobacco and stylo plants with induced expression of both drought
      and cold-responsive genes. Our result suggests that co-expression of SgNCED1 and
      ALO genes is an effective way for use in forage plant improvement for increased
      tolerance to drought and chilling and nutrition quality.

PMID- 25865631
TI  - Intermittent right coronary artery obstruction.
AB  - Although prospectively electrocardiogram-triggered acquisition is frequently used
      for coronary CT angiography examinations in routine clinical practice to achieve
      low radiation dose, the use of retrospectively electrocardiogram-gated techniques
      may be useful for cases that potentially have a dynamic temporal element or
      involve the valves. In this case of a valvular fibroelastoma, CT could
      demonstrate dynamic obstruction of the right coronary ostium. 

PMID- 25865632
TI  - Activation of ERK1/2 is required for the antimitotic activity of the resveratrol
      analogue 3,4,5,4'-tetramethoxystilbene (DMU-212) in human melanoma cells.

PMID- 25865633
TI  - Fetoscopic laser surgery to decompress distal urethral obstruction caused by
      prolapsed ureterocele.
AB  - We report on the successful use of fetoscopic surgery to treat a case of
      prolapsed ureterocele in a female fetus. At 21 weeks' gestation, a double renal
      system with an intravesical ureterocele obstructing the bladder outlet was
      diagnosed, causing severe megacystis, bilateral hydronephrosis and progressive
      oligohydramnios. Ultrasound evaluation following referral to our center confirmed
      severe bilateral hydronephrosis with pelvic and calyceal dilatation, but amniotic
      fluid volume was normal and the ureterocele was not visualized in the bladder.
      Instead, a cystic mass within the external genitalia was observed, suggestive of
      a prolapsed ureterocele, causing intermittently severe obstruction of the
      urethra. The parents were counseled about the uncertain prognosis and fetal
      surgery to decompress the urinary system was proposed. The procedure involved
      firing a contact diode laser until perforation of the ureterocele was achieved.
      Following laser surgery, resolution of megacystis, reduction of hydronephrosis
      and normalization of amniotic fluid volume were observed. Our report demonstrates
      that fetoscopic decompression of a distal urethral obstruction is feasible in the
      rare event of congenital prolapsed ureterocele.

PMID- 25865634
TI  - The Frequency and Outcome of Acute Kidney Injury in a Tertiary Hospital: Which
      Factors Affect Mortality?
AB  - Acute kidney injury (AKI) is a major cause of mortality and morbidity in
      hospitalized patients. Incidence and mortality rates vary from country to
      country, and according to different in-hospital monitoring units and definitions
      of AKI. The aim of this study was to determine factors affecting frequency of AKI
      and mortality in our hospital. We retrospectively evaluated data for 1550
      patients diagnosed with AKI and 788 patients meeting the Kidney Disease:
      Improving Global Outcomes (KDIGO) guideline AKI criteria out of a total of 174
      852 patients hospitalized in our institution between January 1, 2007 and December
      31, 2012. Staging was performed based on KDIGO Clinical Practice for Acute Kidney
      Injury and RIFLE (Risk, Injury, Failure, Loss of kidney function and End-stage
      renal failure). Demographic and biochemical data were recorded and correlations
      with mortality were assessed. The frequency of AKI in our hospital was 0.9%, with
      an in-hospital mortality rate of 34.6%. At multivariate analysis, diastolic blood
      pressure (OR 0.89, 95% CI 0.87-0.92; P < 0.001), monitoring in the intensive care
      unit (OR 0.18, 95% CI 0.09-0.38; P < 0.001), urine output (OR 4.00, 95% CI 2.03
      7.89; P < 0.001), duration of oliguria (OR 1.51, 95% CI 1.34-1.69; P < 0.001),
      length of hospitalization (OR 0.83, 95% CI 0.79-0.88; P < 0.001), dialysis
      requirement (OR 2.30, 95% CI 1.12-4.71; P < 0.05), APACHE II score (OR 1.16, 95%
      CI 1.09-1.24; P < 0.001), and albumin level (OR 0.32, 95% CI 0.21-0.50; P <
      0.001) were identified as independent determinants affecting mortality. Frequency
      of AKI and associated mortality rates in our regional reference hospital were
      compatible with those in the literature. This study shows that KDIGO criteria are
      more sensitive in determining AKI. Mortality was not correlated with staging
      based on RIFLE or KDIGO. Nonetheless, our identification of urine output as one
      of the independent determinants of mortality suggests that this parameter should
      be used in assessing the correlation between staging and mortality. 

PMID- 25865635
TI  - Age at sexual debut in South Africa.
AB  - It is important to understand the age at which sexual relations start in
      designing HIV prevention strategies. Most studies on age of sexual activity of
      young people provide estimated percentages of those that are sexually active in
      specific age groups, and tend either to not provide data for age at sexual debut,
      or to overlook the complexities of analysing data concerning sexual debut. This
      study considers the rate of entry into sexual relations in South Africa by
      providing the median age of women at time of first sexual relations as well as
      other percentiles, and analyses the hypothesis that age at sexual debut has been
      falling. The analysis uses data from the 1998 South African Demographic and
      Health Survey, including a nationally representative sample of 11 735 women, aged
      15 to 49, interviewed in 1998. The analysis uses life-table techniques and
      multivariate analysis. About 8% of the respondents had had sex by age 15. The
      median age at time of first sex was approximately 18 years, and virtually all the
      women had had sex by age 23. There is evidence that the peak of the rate of entry
      into sexual relations occurs at age 18 and that younger cohorts of women are
      entering sexual relations at a younger age. The rate of entry into sexual
      relations is 14% to 20% faster for the younger cohorts, based on information
      given by the older respondents concerning their own behaviour at the same age.
      Age of entry into sexual relations of the women who participated in this study is
      compared to findings of demographic and health surveys in Tanzania and Zimbabwe,
      and rates of entry into marriage are also presented. The lag between entry into
      sexual relations and rate of entry into marriage is compared across countries. It
      appears that, whereas South Africans tend to enter into sexual relations later
      than Tanzanian counterparts and more or less at the same stage as Zimbabweans,
      their rates of entry into marriage are hugely delayed. The consequences for HIV
      infection control are discussed. 

PMID- 25865636
TI  - Differences in Tunisian adolescents' knowledge, misconceptions and attitudes
      towards HIV/AIDS from 1997 to 2002.
AB  - Surveys were conducted to estimate the extent to which knowledge, misconceptions
      and attitudes of adolescents in Tunisia towards HIV/AIDS had changed after a
      period of five years. A population of school-going adolescents of both sexes, age
      16 to 20, was sampled in 1997 and again in 2002. We found that HIV/AIDS and
      sexually transmitted diseases became better known, there was more tolerance
      expressed for people living with AIDS, and the use of condoms was more positively
      judged. Fewer misconceptions surrounding the condition were also noted. However,
      many results recorded during the 1997 survey remained unchanged (e.g., scepticism
      about awareness campaigns; TV as a primary source of information). We discuss the
      socio-economic and medical/social context in Tunisia during the period 1997-2002
      that seemed to allow adolescents to improve their knowledge of HIV/AIDS and to
      acquire positive attitudes towards persons living with the condition. 

PMID- 25865637
TI  - AIDS, order and 'best practice' in the South African workplace: managers, peer
      educators, traditional healers and folk theories.
AB  - This article examines the response of three medium-sized South African
      manufacturing companies to HIV/AIDS. It is argued that the response is heavily
      influenced by managerial conceptions of workplace order - sometimes divergent
      from industrial realities - which results in the selective inclusion and omission
      of best-practice components. The role of peer educators and traditional healers
      within workplace programmes, and the handling of folk theories developed
      independently by workers, are used to illustrate the particular nature of
      workplace responses. Ideologically based selection of best-practice components is
      likely to limit the success of workplace HIV/AIDS programmes and result in slow
      development and improvement. 

PMID- 25865638
TI  - Developmental vulnerabilities and strengths of children living in child-headed
      households: a comparison with children in adult-headed households in equivalent
      impoverished communities.
AB  - This pilot study addresses the need to clarify specific developmental
      vulnerabilities and strengths that characterise children living in child-headed
      households in comparison to children living in adult-headed households in
      equivalent impoverished communities. Samples of 10 each of these two categories
      of household were randomly selected from impoverished communities around
      Pietermaritzburg, South Africa (involving a total of 22 children from a child
      headed households and 41 from an adult-headed households). Fourteen child
      participatory, quantitative and/or qualitative measures were investigated over
      six indicative themes. Differences between the child-headed and adult-headed
      households were statistically or thematically analysed as appropriate to the data
      collected. Specific areas of vulnerability in the former households were access
      to institutional/social services, income (cash or kind) and resource generation,
      unresolved grief, lack of attainable long-term goals, poor self-worth, and poor
      internal locus of control. Specific strengths of children in those households
      were demonstrated in social networking, time and money management, and family
      interactions. 

PMID- 25865639
TI  - Sex, disease and stigma in South Africa: historical perspectives.
AB  - This paper attempts to analyse historically why stigma and denial around HIV/AIDS
      is so powerful in South Africa, so powerful that ailing family members can be
      shunned and evicted. For many observers, the answer lies simply in its being a
      venereal disease, in its connotation with promiscuity and unregulated sexuality.
      We argue that this is not an adequate explanation. Pre-colonial African societies
      were relatively open about sexuality. Though pre-marital and adulterous pregnancy
      certainly caused social disruption, extra-marital sex per se was not stigmatised.
      Even the sexual shame introduced (unevenly) by Christianity and its hybridised
      forms is inadequate in explaining the degree of stigma associated with HIV/AIDS.
      We extend the discussion by exploring the stigma associated with various forms of
      pollution and the inevitability of death. The peculiarly interwoven mixture of
      sexual transgression, pollution and delayed death, we argue, makes HIV/AIDS an
      extraordinarily powerful generator of stigma. 

PMID- 25865640
TI  - Gendered socioeconomic conditions and HIV risk behaviours among young people in
      South Africa.
AB  - Recent evidence suggests that the burden of new HIV infections in sub-Saharan
      Africa is concentrated among young people, especially females. Even in a country
      such as South Africa where knowledge among young people of how to protect oneself
      from infection is rather high, such information may not always be usable in daily
      situations of economic and social disadvantage that characterise many of their
      lives. Despite this possibility, there are surprisingly few definitive studies
      that examine the effects of socioeconomic status on HIV risk and prevention
      behaviours among youth in South Africa. Using household survey data collected in
      2001, this study investigates how socioeconomic disadvantage has influenced the
      sexual behaviour and experiences of 4 000 young women and men aged 14-24 years in
      KwaZulu-Natal province - an area characterised by high HIV prevalence and high
      rates of poverty and inequality. Socioeconomic disadvantage, measured here as low
      relative household wealth, is found to be associated with a variety of unsafe
      sexual behaviours and experiences, particularly for females. Among young women
      low wealth is associated with earlier sexual debut, having had multiple sexual
      partners in the year before the survey, and lower chances of condom use at last
      sex. It is also associated with increased chances that first female sexual
      experience is non-consensual and with higher odds of females having traded sex
      and having experienced physically forced sex. For females and males, low wealth
      reduces the chances of discussing safe-sex practices with the most recent sexual
      partner. Without sufficient attention, during the design and placement of HIV
      prevention programmes, to the gendered economic and social conditions in which
      individuals live - conditions that can make people more or less vulnerable to
      behaviours and experiences that may lead to infection - the potential
      effectiveness of the global response to HIV/AIDS is sacrificed. 

PMID- 25865641
TI  - Social marketing as a means of raising community awareness of an HIV voluntary
      counselling and testing site in Soweto, South Africa.
AB  - In order for HIV voluntary counselling and testing (VCT) to be successful, the
      approval of and attendance at the VCT centre by the community it serves is
      necessary. To this end, the Township AIDS Project (TAP), which has VCT sites
      serving the greater Soweto area, attempts to maintain a high degree of visibility
      in the community through campaigning and various forms of advertising. To
      determine whether the social marketing strategies employed by the organisation
      encouraged attendance, pre-test questionnaires completed by volunteers attending
      the TAP VCT site located in the Meadowlands district of Soweto were
      retrospectively analysed. During 2003, approximately 34% of volunteers were made
      aware of the VCT site through marketing. However, a more important factor in
      volunteer awareness was word of mouth, with about 46% of volunteers informed of
      TAP VCT by a friend, partner or relative. This attests to the success of the
      marketing strategies employed by the TAP organisation in raising community
      awareness and attendance at the VCT site investigated in this study. In total, 1
      141 volunteers completed a questionnaire and 1 054 of these consented to being
      tested for HIV antibodies. The level of infection among the sample of individuals
      tested at this clinic-based VCT programme was 29.9%. 

PMID- 25865642
TI  - Containment and contagion: How to strengthen families to support youth HIV
      prevention in South Africa.
AB  - There has been little research done in South Africa that investigates how
      families nested within communities can be strengthened to support the prevention
      of HIV infection in youth. A focused ethnographic case-study approach was
      employed to better understand how families in a semi-rural area outside Durban,
      South Africa, could support youth to make healthy life choices, particularly with
      respect to HIV risk behaviour. This involved a volunteer convenience sample of
      parents or caregivers and key community members. A psychodynamic extension of
      social representational theory was applied to an interpretation of the data. The
      findings suggest that caregivers of youth feel disempowered and unsupported in a
      context of fractured and un-containing leadership structures, which works against
      social cohesion. In the context of social change and relatively new and
      threatening phenomena such as HIV/AIDS, we argue that strong unified leadership
      structures are necessary to assist with anchoring the unfamiliar and rendering it
      manageable, as well as to form the building blocks of social cohesion, a
      protective social environmental factor for youth. In addition, we suggest that
      programmes aimed at empowering parents or caregivers with knowledge about
      HIV/AIDS as well as renegotiating parental practices to promote greater parental
      authority, would be important interventions at a family level. 

PMID- 25865643
TI  - The impact of reduced drug prices on the cost-effectiveness of HAART in South
      Africa.
AB  - South Africa has started 'rolling out' highly active anti-retroviral therapy
      (HAART) through the public health sector, but implementation has been slow.
      Studies have shown that in Africa AIDS prevention may be more cost-effective than
      providing HAART; such published results provide some support for the South
      African government's apparent reluctance to implement a large-scale rapid HAART
      roll-out. However, previous studies have not linked treatment and prevention
      plans, and do not, for the most part, consider the potential savings to the
      public health sector (e.g., fewer hospital admissions) that may arise from the
      introduction of HAART. The South African costing exercise summarised here avoids
      both these limitations. It provides an update of earlier work and takes into
      account the recent decline in antiretroviral drug prices. It shows that once HIV
      related hospital costs are included in the calculation, the cost per HIV
      infection averted is lower in a treatment-plus-prevention intervention scenario
      than it is in a prevention-only scenario. This suggests that it is economically
      advantageous to fund a large-scale comprehensive intervention plan and that the
      constraints for doing so are political. Once human-rights considerations are
      included, the case for providing HAART is even more compelling. 

PMID- 25865644
TI  - Mid-range shoulder instability modeled as a cam-follower mechanism.
AB  - In this paper, we model a simplified glenohumeral joint as a cam-follower
      mechanism during experimental simulated dislocation. Thus, humeral head
      trajectory and translational forces are predicted using only contact surface
      geometry and compressive forces as function inputs. We demonstrate this new
      interpretation of glenohumeral stability and verify the accuracy of the method by
      physically testing a custom-molded, idealized shoulder model and comparing data
      to the output of the 2D mathematical model. Comparison of translational forces
      between experimental and mathematical approaches resulted in r(2) of 0.88 and
      0.90 for the small and large humeral head sizes, respectively. Comparison of the
      lateral displacement resulted in r(2) of 0.99 and 0.98 for the small and larger
      humeral head sizes, respectively. Comparing translational forces between
      experiments and the mathematical model when varying the compressive force to 30
      N, 60 N, and 90 N resulted in r(2) of 0.90, 0.82, and 0.89, respectively. The
      preliminary success of this study is motivation to introduce the effects of soft
      tissue such as cartilage and validation with a cadaver model. The use of simple
      mathematical models such as this aid in the set-up and understanding of
      experiments in stability research and avoid unnecessary depletion of cadaveric
      resources.

PMID- 25865645
TI  - Investigation of a measles outbreak in Zimbabwe, 2010: potential of a point of
      care test to replace laboratory confirmation of suspected cases.
AB  - Blood and oral fluid (OF) samples were collected from 103 suspected measles cases
      between February and November 2010 during a nationwide measles outbreak in
      Zimbabwe. Siemens measles IgM enzyme immunoassay (EIA) on serum, Microimmune
      measles IgM capture EIA on OF, real-time haemagglutinin (H) gene PCR and nested
      nucleocapsid (N) gene PCR on OF were performed, confirming 75 measles cases.
      These samples were then used to evaluate a newly developed point of care test
      (POCT) for measles and determine its potential for identifying measles cases in
      outbreaks. After performing POCTs on OF samples, nucleic acid was extracted from
      the used test strips and the measles H and N genes amplified by RT-PCR. The
      sensitivity, specificity, positive and negative predictive values of the POCT for
      IgM in OF was 75.0% [95% confidence interval (CI) 63.4-84.5], 96.2% (95% CI 80.4
      99.9), 98.2% (95% CI 90.3-100) and 58.1% (95% CI 42.1-73.0), respectively. The N
      gene sequences showed high level of agreement between original OF and
      corresponding POCT strips. Measles genotype B3 was identified in all cases. We
      conclude that the measles POCT has the potential to be used, at the point of
      contact, in outbreak situations and provide molecular characterization of the
      virus at a later date. 

PMID- 25865646
TI  - Experience with Alemtuzumab, Fludarabine, and Melphalan Reduced-Intensity
      Conditioning Hematopoietic Cell Transplantation in Patients with Nonmalignant
      Diseases Reveals Good Outcomes and That the Risk of Mixed Chimerism Depends on
      Underlying Disease, Stem Cell Source, and Alemtuzumab Regimen.
AB  - Alemtuzumab, fludarabine, and melphalan reduced-intensity conditioning (RIC)
      regimens are increasingly used for the hematopoietic cell transplantation (HCT)
      of pediatric and young adult patients with nonmalignant diseases. Early
      experience suggests that these regimens are associated with good survival but a
      high incidence of mixed chimerism, which we have previously shown to be
      influenced by the alemtuzumab schedule. We hypothesized that the underlying
      diagnosis and donor graft source would also affect the development of mixed
      chimerism and that the majority of patients would survive RIC HCT without graft
      loss. To examine this, we conducted a retrospective study of 206 patients with
      metabolic diseases, non-Fanconi anemia marrow failure disorders, and primary
      immune deficiencies who underwent 210 consecutive RIC HCT procedures at
      Cincinnati Children's Hospital. Ninety-seven percent of the patients engrafted.
      Mixed donor and recipient chimerism developed in 46% of patients. Patients with
      marrow failure had a low risk of mixed chimerism (hazard ratio [HR], .208; 95%
      confidence interval [CI], .061 to .709; P = .012). The risk of mixed chimerism
      was high in patients who received a cord blood graft (HR, 3.122; 95% CI, 1.236 to
      7.888; P = .016). As expected, patients who received a proximal or higher dose
      per kilogram of alemtuzumab schedule also experienced higher rates of mixed
      chimerism (all HR > 2, all P < .05). At the time of last follow-up (median, 654
      days; range, 13 to 3337), over 75% of patients had greater than 90% whole blood
      donor chimerism. A second transplantation was performed in 5% of patients. Three
      year survival without retransplantation was 84% (95% CI, 71% to 98%) for patients
      who underwent transplantation with an HLA-matched sibling donor. Survival without
      retransplantation was negatively affected by lack of a matched related donor,
      increasing age, and development of grades III and IV acute graft-versus-host
      disease. We conclude that alemtuzumab, fludarabine, and melphalan RIC HCT offers
      good results for many patients and that the risk of developing mixed chimerism is
      influenced by underlying diagnosis, graft source, and alemtuzumab dosing.

PMID- 25865647
TI  - Evaluation of Initial Telomere Length and Changes after Transplantation in Adult
      Double-Unit Cord Blood Transplant Recipients.
AB  - Cord blood (CB) leukocytes have inherent telomere length (TL) variation, and CB
      hematopoietic stem cells (HSC) can maintain high telomerase levels preventing
      telomere attrition in vitro. We evaluated TL changes in 13 adult double-unit CB
      transplant (CBT) recipients. In the 26 units, we observed a marked variation in
      CB TL at thaw (median, 9.99 kilobases [kb]; range, 6.85 to 13.5). All 13 patients
      engrafted. Of 11 engrafting with 1 unit, there was no correlation between unit
      dominance and TL (mean dominant unit TL, 8.84 kb +/- 1.76; mean nonengrafting
      unit TL, 10.3 kb +/- 1.81; P = .77). Serial measurements of TL up to 1 year after
      CBT demonstrated an overall mean 3.04 kb +/- .16 TL decrease with only 1 patient
      exhibiting telomere maintenance. In summary, initial TL does not predict CB unit
      dominance. Moreover, our analysis suggests neonatal hematopoiesis makes a
      transition to an HSC characterized by changes in average TL and potentially low
      telomerase asymmetric cell division in adult CBT recipients. Further
      investigation of alterations in telomere length and its clinical implications
      after transplantation of this observation are indicated. 

PMID- 25865648
TI  - Allogeneic Hematopoietic Stem Cell Transplantation Is an Effective Salvage
      Therapy for Patients with Chronic Myeloid Leukemia Presenting with Advanced
      Disease or Failing Treatment with Tyrosine Kinase Inhibitors.
AB  - Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only known
      curative therapy for chronic myeloid leukemia (CML); however, it is rarely
      utilized given the excellent long-term results with tyrosine kinase inhibitor
      (TKI) treatment. The purpose of this study is to examine HSCT outcomes for
      patients with CML who failed TKI therapy or presented in advanced phase and to
      identify predictors of survival, relapse, and nonrelapse mortality (NRM). Fifty
      one patients with CML underwent HSCT for advanced disease at diagnosis (n = 15),
      TKI resistance as defined by the European LeukemiaNet guidelines (n = 30), TKI
      intolerance (n = 2), or physician preference (n = 4). At a median follow-up of
      71.9 months, the 8-year overall survival (OS), event-free survival (EFS),
      relapse, and NRM were 68%, 46%, 41%, and 23%, respectively. In univariate
      analysis, predictors of OS included first chronic phase (CP1) disease status at
      HSCT (P = .0005), European Society for Blood and Marrow Transplantation score 1
      to 4 (P = .04), and complete molecular response (CMR) to HSCT (P < .0001). Donor
      (female) to patient (male) gender combination (P = .02) and CMR to HSCT (P <
      .0001) predicted lower relapse. In multivariate analysis, CMR to HSCT remained an
      independent predictor of OS (odds ratio [OR], 43), EFS (OR, 56) and relapse (OR,
      29). This report indicates that the outlook is excellent for those patients who
      remain in CP1 at the time of HSCT and achieve a CMR after HSCT. However, only
      approximately 50% of those in advanced phase at HSCT are long-term survivors.
      This highlights the ongoing need to try to identify patients earlier, before
      disease progression, who are destined to fail this treatment to optimize
      transplantation outcomes.

PMID- 25865649
TI  - Physical Activity, Fitness, and Cardiometabolic Risk Factors in Adult Survivors
      of Childhood Cancer with a History of Hematopoietic Cell Transplantation.
AB  - Along with other childhood cancer survivors (CCS), hematopoietic cell
      transplantation (HCT) survivors are at high risk of treatment-related late
      effects, including cardiovascular disease and diabetes. Cardiometabolic risk
      factor abnormalities may be exacerbated by inadequate physical activity (PA).
      Relationships between PA and cardiometabolic risk factors have not been well
      described in CCS with HCT. PA (self reported), mobility (timed up and go test),
      endurance (6-minute walk test), handgrip strength, and cardiometabolic risk
      factors were measured in 119 HCT survivors and 66 sibling controls ages >=18
      years. Adjusted comparisons between HCT survivors and controls and between
      categories of low and high PA, mobility, endurance, and strength were performed
      with linear regression. Among HCT survivors, the high PA group had lower waist
      circumference (WC) (81.9 +/- 2.5 versus 88.6 +/- 3.1 cm +/- standard error (SE),
      P = .009) than the low PA group, whereas the high endurance group had lower WC
      (77.8 +/- 2.6 versus 87.8 +/- 2.5 cm +/- SE, P = .0001) and percent fat mass
      (33.6 +/- 1.8 versus 39.4 +/- 1.7% +/- SE, P = .0008) and greater insulin
      sensitivity (IS) (10.9 +/- 1.0 versus 7.42 +/- 1.14 mg/kg/min +/- SE via
      euglycemic insulin clamp, P = .001) than the low endurance group. Differences
      were greater in HCT survivors than in controls for WC between low and high PA
      groups, triglycerides between low and high mobility groups, and WC, systolic
      blood pressure, and IS between low and high endurance groups (all Pinteraction
      <.05). Higher endurance was associated with a more favorable cardiometabolic
      profile in HCT survivors, suggesting that interventions directed to increase
      endurance in survivors may reduce the risk of future cardiovascular disease. 

PMID- 25865651
TI  - [Corneal morphometric predictive models from ametropia to excimer laser
      treatment].
AB  - OBJECTIVE: To develop corneal morphometric models with refractive error in
      excimer laser surgery. METHOD: A prospective-longitudinal study was conducted on
      78 patients (151 eyes) using the LASIK surgical technique, and 56 patients (111
      eyes) with myopic astigmatism using ESIRIS (Schwind-Germany) equipment with
      pendulous microkeratome. The results were analyzed using descriptive statistics.
      A NIDEK Confoscan microscope was used to obtain and study the images. RESULTS:
      After LASIK treatment 84.3% of the variations in epithelium thickness variations
      were due to the magnitude of refractive error and the epithelium thickness before
      LASIK treatment. More than two-thirds (68.8%) of the variations in keratocyte
      density variations in posterior flap and 48.2% of the variations in the anterior
      retroablation zone were due to the magnitude of the refractive error. Variations
      of 90% were found in the corneal thickness after LASEK, which were due to the
      magnitude of the refractive error before LASEK. CONCLUSIONS: Predictive models
      reveal that morphometrical variations depend of the magnitude of the refractive
      error. These models are very important in the selection of patient for refractive
      surgery, and also for the specific technique to use.

PMID- 25865650
TI  - Transplantation Outcomes for Children with Hypodiploid Acute Lymphoblastic
      Leukemia.
AB  - Children with hypodiploid acute lymphoblastic leukemia (ALL) have inferior
      outcomes despite intensive risk-adapted chemotherapy regimens. We describe 78
      children with hypodiploid ALL who underwent hematopoietic stem cell
      transplantation between 1990 and 2010. Thirty-nine (50%) patients had <= 43
      chromosomes, 12 (15%) had 44 chromosomes, and 27 (35%) had 45 chromosomes. Forty
      three (55%) patients underwent transplantation in first remission (CR1) and 35
      (45%) underwent transplantation in >= second remission (CR2). Twenty-nine
      patients (37%) received a graft from a related donor and 49 (63%) from an
      unrelated donor. All patients received a myeloablative conditioning regimen. The
      5-year probabilities of leukemia-free survival, overall survival, relapse, and
      treatment-related mortality for the entire cohort were 51%, 56%, 27%, and 22%,
      respectively. Multivariate analysis confirmed that mortality risks were higher
      for patients who underwent transplantation in CR2 (hazard ratio, 2.16; P = .05),
      with number of chromosomes <= 43 (hazard ratio, 2.15; P = .05), and for those who
      underwent transplantation in the first decade of the study period (hazard ratio,
      2.60; P = .01). Similarly, treatment failure risks were higher with number of
      chromosomes <= 43 (hazard ratio, 2.28; P = .04) and the earlier transplantation
      period (hazard ratio, 2.51; P = .01). Although survival is better with advances
      in donor selection and supportive care, disease-related risk factors
      significantly influence transplantation outcomes. 

PMID- 25865652
TI  - [Comparative study of clinical features between unilateral and bilateral orbital
      IgG4-related disease].
AB  - OBJECTIVE: Descriptive and comparative study of patients with orbital IgG4
      related disease. MATERIAL AND METHODS: A review and analysis of the cases
      diagnosed with inflammatory orbital lesion related to IgG4 by the Ophthalmic
      Pathology Service in the Dr. Luis Sanchez Bulnes Hospital. RESULTS: A total of 9
      cases were found, in which 66% were women, and with a mean age of 48 years and
      time to diagnosis of 2 years. Unilateral involvement was observed in 56% of
      cases. All the females experienced pain, and there was an optimal response to
      corticosteroid treatment in 100% of patients who required medical treatment (one
      case showed spontaneous resolution). In bilateral cases (44%), only 25% were
      female, and none had pain as a presenting symptom. Furthermore, 25% of these
      patients required a combination with immunosuppressants to control inflammation.
      CONCLUSIONS: Clinical presentation of patients with unilateral orbital IgG4
      related disease differs from those with bilateral involvement.

PMID- 25865653
TI  - Escherichia coli populations in unpredictably fluctuating environments evolve to
      face novel stresses through enhanced efflux activity.
AB  - There is considerable understanding about how laboratory populations respond to
      predictable (constant or deteriorating environment) selection for single
      environmental variables such as temperature or pH. However, such insights may not
      apply when selection environments comprise multiple variables that fluctuate
      unpredictably, as is common in nature. To address this issue, we grew replicate
      laboratory populations of Escherichia coli in nutrient broth whose pH and
      concentrations of salt (NaCl) and hydrogen peroxide (H2 O2 ) were randomly
      changed daily. After ~170 generations, the fitness of the selected populations
      had not increased in any of the three selection environments. However, these
      selected populations had significantly greater fitness in four novel environments
      which have no known fitness-correlation with tolerance to pH, NaCl or H2 O2 .
      Interestingly, contrary to expectations, hypermutators did not evolve. Instead,
      the selected populations evolved an increased ability for energy-dependent efflux
      activity that might enable them to throw out toxins, including antibiotics, from
      the cell at a faster rate. This provides an alternate mechanism for how
      evolvability can evolve in bacteria and potentially lead to broad-spectrum
      antibiotic resistance, even in the absence of prior antibiotic exposure. Given
      that environmental variability is increasing in nature, this might have serious
      consequences for public health.

PMID- 25865654
TI  - Reduced Dose Intensities of Doxorubicin in Elderly Patients with DLBCL in
      Rituximab Era.
AB  - PURPOSE: The dose intensity of doxorubicin (DID) is important to the survival of
      diffuse large B cell lymphoma (DLBCL) patients. However, due to expected
      toxicities, most elderly patients cannot receive full doses of anthracyclines.
      The purpose of this study was to evaluate the effect of DID on the survival of
      elderly DLBCL patients (age >= 70 years) in the rituximab era. MATERIALS AND
      METHODS: We analyzed 433 DLBCL patients who were treated with R-CHOP between
      December 2003 and October 2011 at the Seoul National University Hospital. Of
      these patients, 19.2% were aged >= 70 years. We analyzed the survival outcomes
      according to DID. RESULTS: Significantly poorer overall survival (OS) was
      observed for patients aged >= 70 years (2-year OS rate: 59.9% vs. 84.2%; p <
      0.001). DID <= 10 mg/m(2)/wk had a significant effect on the OS and progression
      free survival (PFS) in elderly patients (2-year OS rate: 40.0% in DID <= 10
      mg/m(2)/wk vs. 62.6% in DID > 10 mg/m(2)/wk; p=0.031; 2-year PFS: 35.0% vs.
      65.7%; p=0.036). The OS on each 1.7 mg/m(2)/wk doxorubicin increment above 10
      mg/m(2)/wk in elderly patients was not significant among the groups (2-year OS
      rate: 75.0% in DID 10.0-11.7 mg/m(2)/wk vs. 66.7% in DID 15.0-16.7 mg/m(2)/wk;
      p=0.859). Treatment related mortality was not related to DID. CONCLUSION: DID can
      be reduced up to 10 mg/m(2)/wk in elderly DLBCL patients in the rituximab era.
      Maintenance of DID > 10 mg/m(2)/wk and judicious selection of elderly patients
      who are tolerant to DID is necessary.

PMID- 25865655
TI  - Impact of Molecular Subtype Conversion of Breast Cancers after Neoadjuvant
      Chemotherapy on Clinical Outcome.
AB  - PURPOSE: The aim of this study was to examine molecular subtype conversions in
      patients who underwent neoadjuvant chemotherapy (NAC) and analyze their clinical
      implications. MATERIALS AND METHODS: We included consecutive breast cancer
      patients who received NAC at the National Cancer Center, Korea, between August
      2002 and June 2011, and had available data on estrogen receptor (ER),
      progesterone receptor (PR), and human epidermal growth factor 2 (HER2) receptor
      status prior to NAC. Molecular subtypes, hormone receptor (HR) status, and ER and
      PR Allred scores before and after NAC were compared, and the long-term outcomes
      were analyzed. RESULTS: Of 322 patients, 32 (9.9%) achieved a pathologic complete
      response after NAC. HR+/HER2- tumors tended to convert into triple negative (TN)
      tumors (10.3%), whereas 34.6% of TN tumors gained HR positivity to become
      HR+/HER2- tumors. Clinical outcomes of molecular subtype conversion groups were
      compared against patients who remained as HR+/HER2- throughout. The HR+/HER2- to
      TN group had significantly poorer recurrence-free survival (RFS) (hazard ratio,
      3.54; 95% confidence interval [CI], 1.60 to 7.85) and overall survival (OS)
      (hazard ratio, 3.73; 95% CI, 1.34 to 10.38). Patients who remained TN throughout
      had the worst outcomes (for RFS: hazard ratio, 3.70; 95% CI, 1.86 to 7.36; for
      OS: hazard ratio, 5.85; 95% CI, 2.53 to 13.51), while those who converted from TN
      to HR+/HER2-showed improved comparable survival outcomes. CONCLUSION: Molecular
      subtypes of breast cancers changed frequently after NAC, resulting in different
      tumor prognostication. Tumor subtyping should be repeated after NAC in patients
      with breast cancer.

PMID- 25865656
TI  - Triplex molecular beacons for sensitive recognition of melamine based on abasic
      site-containing DNA and fluorescent silver nanoclusters.
AB  - A melamine aptamer derived from an abasic-site-containing triplex molecular
      beacon (tMB) was designed and developed for sensitive recognition of melamine by
      integrating tMBs and fluorescent silver nanoclusters (Ag NCs). 

PMID- 25865657
TI  - Optimization of cultural conditions for biosurfactant production by Pleurotus
      djamor in solid state fermentation.
AB  - Being eco-friendly, less toxic, more biodegradable and biocompatible, biological
      surfactants have higher activity and stability compared to synthetic ones. In
      spite of the fact that there are abundant benefits of biosurfactants over the
      synthetic congeners, the problem related with the economical and large scale
      production proceeds. The utilization of several industrial wastes in the
      production media as substrates reduces the production cost. This current study
      aims optimization of biosurfactant production conditions by Pleurotus djamor,
      grown on sunflower seed shell, grape wastes or potato peels as renewable cheap
      substrates in solid state fermentation. After determination of the best substrate
      for biosurfactant production, we indicate optimum size and amount of solid
      substrate, volume of medium, temperature, pH and Fe(2+) concentrations on
      biosurfactant production. In optimum conditions, by reducing water surface
      tension to 28.82 +/- 0.3 mN/m and having oil displacement diameter of 3.9 +/- 0.3
      cm, 10.205 +/- 0.5 g/l biosurfactant was produced. Moreover, chemical composition
      of biosurfactant produced in optimum condition was determined by FTIR. Lastly,
      laboratory's large-scale production was carried out in optimum conditions in a
      tray bioreactor designed by us and 8.9 +/- 0.5 g/l biosurfactant was produced
      with a significant surface activity (37.74 +/- 0.3 mN/m). With its economical
      suggestions and applicability of laboratory's large-scale production, this work
      indicates the possibility of using low cost agro-industrial wastes as renewable
      substrates for biosurfactant production. Therefore, using economically produced
      biosurfactant will reduce cost in several applications such as bioremediation,
      oil recovery and biodegradation of toxic chemicals. 

PMID- 25865658
TI  - Septic arthritis or juvenile idiopathic arthritis--the case of a 2 year old boy.

PMID- 25865660
TI  - Portion size and intended consumption. Evidence for a pre-consumption portion
      size effect in males?
AB  - Larger portions increase energy intake (the 'portion size effect'); however, the
      mechanisms behind this effect are unclear. Although pre-meal intentions are
      thought to be an important determinant of energy intake, little research has
      examined how much of a meal individuals intend to eat when served standard versus
      larger portion sizes. Three studies examined the effect of manipulating portion
      size on intended food consumption. In Studies 1 (spaghetti bolognese) and 2
      (curry and rice) male participants were shown an image of either a standard or a
      larger meal and indicated how much of the meal they intended to consume. In Study
      3 male and female participants were served either a standard or a larger portion
      of ice cream for dessert, they indicated how much they intended to consume and
      then ate as much of the ice cream as they desired. Regardless of being shown
      standard or large portion sizes, in Studies 1 and 2 participants reported that
      they intended to eat the majority of the meal, equating to a large difference in
      intended energy consumption between portion size conditions (a 'pre-consumption
      portion size effect'). This finding was replicated in male participants in Study
      3, although females intended to eat a smaller proportion of the larger portion of
      ice cream, compared to the standard portion. Both male and female participants
      tended to eat in accordance with their pre-meal intentions and a portion size
      effect on actual consumption was subsequently observed in males, but not in
      females. The portion size effect may be observed when measuring pre-meal intended
      consumption in males. 

PMID- 25865659
TI  - The relation of saturated fats and dietary cholesterol to childhood cognitive
      flexibility.
AB  - Identification of health behaviors and markers of physiological health associated
      with childhood cognitive function has important implications for public health
      policy targeted toward cognitive health throughout the life span. Although
      previous studies have shown that aerobic fitness and obesity exert contrasting
      effects on cognitive flexibility among prepubertal children, the extent to which
      diet plays a role in cognitive flexibility has received little attention.
      Accordingly, this study examined associations between saturated fats and
      cholesterol intake and cognitive flexibility, assessed using a task switching
      paradigm, among prepubertal children between 7 and 10 years (N = 150). Following
      adjustment of confounding variables (age, sex, socioeconomic status, IQ, VO2max,
      and BMI), children consuming diets higher in saturated fats exhibited longer
      reaction time during the task condition requiring greater amounts of cognitive
      flexibility. Further, increasing saturated fat intake and dietary cholesterol
      were correlated with greater switch costs, reflecting impaired ability to
      maintain multiple task sets in working memory and poorer efficiency of cognitive
      control processes involved in task switching. These data are among the first to
      indicate that children consuming diets higher in saturated fats and cholesterol
      exhibit compromised ability to flexibly modulate their cognitive operations,
      particularly when faced with greater cognitive challenge. Future longitudinal and
      intervention studies are necessary to comprehensively characterize the
      interrelationships between diet, aerobic fitness, obesity, and children's
      cognitive abilities. 

PMID- 25865661
TI  - Greater perceived ability to form vivid mental images in individuals with high
      compared to low BMI.
AB  - Obese individuals report more frequent food cravings than their lean
      counterparts. Since mental imagery plays a role in eliciting and maintaining
      craving we hypothesized that one's ability to image may be associated with body
      mass index (BMI) and account, at least in part, for the association between BMI
      and craving. Twenty-five participants (BMI range: 17.7 kg/m(2)-34.2 kg/m(2))
      completed three measures of perceived mental imagery ability (The Vividness of
      Visual Imagery Questionnaire, The Vividness of Olfactory Imagery Questionnaire,
      The Vividness of Food Imagery Questionnaire), and one measure of craving (Food
      Craving Inventory). As predicted, correlation analyses revealed positive
      associations between BMI and perceived ability to image odors and foods, but not
      visual objects. Olfactory imagery was singled out as the best predictor of BMI in
      a hierarchical regression analysis. A second experiment with 57 participants (BMI
      range: 19.1 kg/m(2)-38.7 kg/m(2)) then confirmed the significant positive
      association between BMI and perceived ability to image odors. These results raise
      the possibility that imagery ability may play a role in the heightened food cue
      reactivity observed in obese individuals.

PMID- 25865662
TI  - Perceptions of university students regarding calories, food healthiness, and the
      importance of calorie information in menu labelling.
AB  - This study investigated Brazilian university students' perceptions of the concept
      of calories, how it relates to food healthiness, and the role of calorie
      information on menus in influencing food choices in different restaurant
      settings. Focus groups were conducted with 21 undergraduate students from various
      universities. Transcriptions were analysed for qualitative content, by coding and
      grouping words and phrases into similar themes. Two categories were obtained:
      Calorie concept and connection to healthiness; and Calorie information and food
      choices in restaurants. Calories were understood as energy units, and their
      excessive intake was associated with weight gain or fat gain. However, food
      healthiness was not associated to calorie content, but rather to food composition
      as a whole. Calorie information on restaurant menus was not considered enough to
      influence food choices, with preferences, dietary restrictions, food composition,
      and even restaurant type mentioned as equally or more important. Only a few
      participants mentioned using calorie information on menus to control food intake
      or body weight. Students' discussions were suggestive of an understanding of
      healthy eating as a more complex issue than calorie-counting. Discussions also
      suggested the need for more nutrition information, besides calorie content, to
      influence food choices in restaurants. 

PMID- 25865663
TI  - Rationalizing meat consumption. The 4Ns.
AB  - Recent theorizing suggests that the 4Ns - that is, the belief that eating meat is
      natural, normal, necessary, and nice - are common rationalizations people use to
      defend their choice of eating meat. However, such theorizing has yet to be
      subjected to empirical testing. Six studies were conducted on the 4Ns. Studies 1a
      and 1b demonstrated that the 4N classification captures the vast majority (83%
      91%) of justifications people naturally offer in defense of eating meat. In Study
      2, individuals who endorsed the 4Ns tended also to objectify (dementalize)
      animals and included fewer animals in their circle of moral concern, and this was
      true independent of social dominance orientation. Subsequent studies (Studies 3
      5) showed that individuals who endorsed the 4Ns tend not to be motivated by
      ethical concerns when making food choices, are less involved in animal-welfare
      advocacy, less driven to restrict animal products from their diet, less proud of
      their animal-product decisions, tend to endorse Speciesist attitudes, tend to
      consume meat and animal products more frequently, and are highly committed to
      eating meat. Furthermore, omnivores who strongly endorsed the 4Ns tended to
      experience less guilt about their animal-product decisions, highlighting the
      guilt-alleviating function of the 4Ns. 

PMID- 25865664
TI  - Nutritional advice from George Orwell. Exploring the social mechanisms behind the
      overconsumption of unhealthy foods by people with low socio-economic status.
AB  - Despite a general consensus and recognition of the importance of the "social
      gradient" on nutritional standards and ultimately people's health, (Budrys, 2003;
      Marmot & Wilkinson, 1999; Marmot et al., 1991; Ross & Wu, 1995), the body of
      literature identifying and describing the actual underlying social mechanisms
      which could explain this association is small, fragmented and not contained
      within one single discipline of thought - the effects of this conundrum seem
      easier to describe than to explain. The aim of this article is therefore to
      explore and identify social mechanisms, which could help explain why people with
      low socio-economic status consume a disproportionate amount of unhealthy foods
      and therefore also observe poorer diets. It is therefore in many ways an
      exploration into the nature of (relative) poverty. The point of departure for
      this exploration and identification is historical descriptions (in the form of
      excerpts) from George Orwell's (1937) book "The Road to Wigan Pier" on the living
      conditions of the British working classes. These descriptions will be aligned
      with results from contemporary research into nutritional behaviour. Strong
      similarities are identified between George Orwell's historical descriptions of
      the working-class's unhealthy diet and the findings from contemporary research
      into nutritional behaviour of people with a low socio-economic status. Certain
      social mechanisms influencing nutritional choices are readily identifiable across
      disciplines, and even partly reproduced in different historical, social and
      spatial contexts, with stronger negative (nutritional) consequences for people
      with low socio-economic status. The disregard of social mechanisms, and therefore
      implicitly issues of class, could indicate a general "de-socialization" of
      nutritional advice also in its dispersal through various health-promotion
      initiatives and campaigns, which raises serious questions about the usefulness of
      much nutritional advice, already tentatively questioned by some nutritionist
      (Burr et al., 2007) as well as "food" sociologist (Smith & Holm, 2010). 

PMID- 25865665
TI  - Confirmatory factor analysis of the Feeding Emotions Scale. A measure of parent
      emotions in the context of feeding.
AB  - Assessing parent affect is important because studies examining the parent-child
      dyad have shown that parent affect has a profound impact on parent-child
      interactions and related outcomes. Although some measures that assess general
      affect during daily lives exist, to date there are only few tools that assess
      parent affect in the context of feeding. The aim of this study was to develop an
      instrument to measure parent affect specific to the feeding context and determine
      its validity and reliability. A brief instrument consisting of 20 items was
      developed that specifically asks how parents feel during the feeding process.
      This brief instrument draws on the structure of a well-validated general affect
      measure. A total of 296 Hispanic and Black Head Start parents of preschoolers
      completed the Feeding Emotions Scale along with other parent-report measures as
      part of a larger study designed to better understand feeding interactions during
      the dinner meal. Confirmatory factor analysis supported a two-factor model with
      independent subscales of positive affect and negative affect (Cronbach's alphas
      of 0.85 and 0.84, respectively). Concurrent and convergent construct validity was
      evaluated by correlating the subscales of the Feeding Emotions Scale with
      positive emotionality and negative emotionality from the Differential Emotions
      Scale - a measure of general adult emotions. Concurrent and convergent criterion
      validity was evaluated by testing mean differences in affect across parent
      feeding styles using ANOVA. A significant difference was found across maternal
      weight status for positive feeding affect. The resulting validated measure can be
      used to assess parent affect in studies of feeding to better understand how
      interactions during feeding may impact the development of child eating behaviors
      and possibly weight status. 

PMID- 25865666
TI  - Savouring morality. Moral satisfaction renders food of ethical origin
      subjectively tastier.
AB  - Past research has shown that the experience of taste can be influenced by a range
      of external cues, especially when they concern food's quality. The present
      research examined whether food's ethicality - a cue typically unrelated to
      quality - can also influence taste. We hypothesised that moral satisfaction with
      the consumption of ethical food would positively influence taste expectations,
      which in turn will enhance the actual taste experience. This enhanced taste
      experience was further hypothesised to act as a possible reward mechanism
      reinforcing the purchase of ethical food. The resulting ethical food -> moral
      satisfaction  -> enhanced taste expectations and experience -> stronger
      intentions to buy/willingness to pay model was validated across four studies: one
      large scale international survey (Study 1) and three experimental studies
      involving actual food consumption of different type of ethical origin - organic
      (Study 2), fair trade (Study 3a) and locally produced (Study 3b). Furthermore,
      endorsement of values relevant to the food's ethical origin moderated the effect
      of food's origin on moral satisfaction, suggesting that the model is primarily
      supported for people who endorse these values. 

PMID- 25865667
TI  - The mediating role of emotion dysregulation and depression on the relationship
      between childhood trauma exposure and emotional eating.
AB  - Exposure to childhood adversity is implicated in the etiology of adverse health
      outcomes, including depression, posttraumatic stress disorder (PTSD), and
      obesity. The relationship between childhood trauma and obesity may be related to
      the association of childhood trauma and risk for emotional eating. One pathway
      between trauma exposure, psychopathology, and emotional eating may be through
      emotion dysregulation and depression. The current study was undertaken to
      characterize demographic, environmental, and psychological risk factors for
      emotional eating in a primarily African American, low socioeconomic status (SES),
      inner-city population (N = 1110). Emotional eating was measured using the Dutch
      Eating Behavioral Questionnaire and the Emotional Dysregulation Scale was used to
      assess emotion regulation. The Beck Depression Inventory and the modified PTSD
      Symptom Scale were used to assess depression and PTSD, respectively. Higher
      levels of emotional eating were associated with body mass index, income,
      childhood and adulthood trauma exposure, depressive and PTSD symptoms, negative
      affect and emotion dysregulation. Childhood emotional abuse was the most
      associated with emotional eating in adulthood. Hierarchical linear regression and
      mediation analyses indicated that the association between childhood trauma
      exposure (and emotional abuse specifically) and emotional eating was fully
      mediated by depression symptoms and emotion dysregulation, with emotional
      dysregulation contributing more to the mediation effect. Together these findings
      support a model in which obesity and related adverse health outcomes in stress-
      and trauma-exposed populations may be directly related to self-regulatory coping
      strategies accompanying emotion dysregulation. Our data suggest that emotion
      dysregulation is a viable therapeutic target for emotional eating in at-risk
      populations. 

PMID- 25865668
TI  - A role for Kalirin-7 in nociceptive sensitization via activity-dependent
      modulation of spinal synapses.
AB  - Synaptic plasticity is the cornerstone of processes underlying persistent
      nociceptive activity-induced changes in normal nociceptive sensitivity. Kalirin-7
      is a multifunctional guanine-nucleotide-exchange factor (GEF) for Rho GTPases
      that is characterized by its localization at excitatory synapses, interactions
      with glutamate receptors and its ability to dynamically modulate the neuronal
      cytoskeleton. Here we show that spinally expressed Kalirin-7 is required for
      persistent nociceptive activity-dependent synaptic long-term potentiation as well
      as activity-dependent remodelling of synaptic spines in the spinal dorsal horn,
      thereby orchestrating functional and structural plasticity during the course of
      inflammatory pain. 

PMID- 25865669
TI  - Elucidating the prognostic significance of KRAS, NRAS, BRAF and PIK3CA mutations
      in Chinese patients with metastatic colorectal cancer.
AB  - AIM: The prognostic significance of KRAS, NRAS, PIK3CA and BRAF mutations was
      evaluated in Chinese patients with metastatic colorectal cancer (CRC). METHOD:
      Tumor samples from 183 patients were retrospectively tested for KRAS, NRAS,
      PIK3CA and BRAF mutations. Multivariate analysis was performed to determine the
      relationship between mutational status, drug response and survival. RESULT: Over
      70% of patients received two or more lines of chemotherapy, 50% had cetuximab and
      18% had bevacizumab. The prevalence of KRAS, NRAS, BRAF and PIK3CA mutations was
      45, 3.2, 5 and 20%, respectively. For the entire cohort, the median overall
      survival was 24 months (95% confidence interval [CI] = 20.4-26.4 months). Of the
      genes tested, only KRAS mutation was an independent prognostic factor with a
      multivariate hazard ratio of 1.5 (95% CI = 1.05-2.16, P = 0.03). In the subgroup
      of patients who received cetuximab-based therapy in the first-line setting, KRAS
      mutation was associated with a lack of response to chemotherapy (28% vs 66%, chi
      square, P = 0.01). Patients with KRAS mutant tumors (or KRAS wild-type tumors
      that harbored BRAF and/or PIK3CA mutations) tended to have lower response rates
      to chemotherapy and/or cetuximab (P = not significant). The number of NRAS mutant
      cases was too small to allow any statistical analysis. CONCLUSION: The prevalence
      of KRAS, NRAS, BRAF and PIK3CA mutations in this cohort is consistent with
      reports from non-Asian populations, and KRAS mutation has both prognostic and
      predictive significance in Chinese patients with metastatic CRC.

PMID- 25865670
TI  - Physiological adjustment to salt stress in Jatropha curcas is associated with
      accumulation of salt ions, transport and selectivity of K+, osmotic adjustment
      and K+/Na+ homeostasis.
AB  - This study assessed the capacity of Jatropha curcas to physiologically adjust to
      salinity. Seedlings were exposed to increasing NaCl concentrations (25, 50, 75
      and 100 mm) for 15 days. Treatment without NaCl was adopted as control. Shoot dry
      weight was strongly reduced by NaCl, reaching values of 35% to 65% with 25 to 100
      mm NaCl. The shoot/root ratio was only affected with 100 mm NaCl. Relative water
      content (RWC) increased only with 100 mm NaCl, while electrolyte leakage (EL) was
      much enhanced with 50 mm NaCl. The Na(+) transport rate to the shoot was more
      affected with 50 and 100 mm NaCl. In parallel, Cl(-) transport rate increased
      with 75 and 100 mm NaCl, while K(+) transport rate fell from 50 mm to 100 mm
      NaCl. In roots, Na(+) and Cl(-) transport rates fell slightly only in 50 mm (to
      Na(+)) and 50 and 100 mm (to Cl(-)) NaCl, while K(+) transport rate fell
      significantly with increasing NaCl. In general, our data demonstrate that J.
      curcas seedlings present changes in key physiological processes that allow this
      species to adjust to salinity. These responses are related to accumulation of
      Na(+) and Cl(-) in leaves and roots, K(+)/Na(+) homeostasis, transport of K(+)
      and selectivity (K-Na) in roots, and accumulation of organic solutes contributing
      to osmotic adjustment of the species.

PMID- 25865671
TI  - Effects of iron-glycine chelate on growth, carcass characteristic, liver mineral
      concentrations and haematological and biochemical blood parameters in broilers.
AB  - Studies were carried out to determine the effect of additive iron-glycine chelate
      on the production performance, slaughter yield, mineral deposition in the liver
      and the metabolic blood panel in broiler chickens. A total of 250 one-day-old
      Ross 308 chicks were allotted into five groups with five replicates of 10 birds
      each. Diets were supplemented with the organic form iron (Fe-Gly at the rate of
      25%, 50% or 100% of the total requirements of the elements) and inorganic Fe
      (FeSO4 at the rate of 50% or 100%). In the experiment, iron was added to the
      premix (containing no Fe) in an amount of 40 or 20 mg per kg of basal diet, in
      groups I and II, in the form of FeSO4 , and in an amount of 40, 20 or 10 mg per
      kg of basal diet, in groups III, IV and V, in the form of Fe-Gly. The study
      covering the period from the first to the 42nd day of breeding revealed that the
      production performance and slaughter yield were not dependent on the form and
      amount of added Fe. In the experimental groups with the addition of Fe-Gly of 20
      or 10 mg/kg, there were no deaths of chickens during the whole fattening period.
      As a result, introducing an organic form of iron covering 50% and 25% of the
      birds' requirement increased the effectiveness of chicken fattening (European
      Efficiency Index) (p < 0.01). An organic Fe compound (40, 20 or 10 mg/kg) added
      to mixtures contributed to significant changes in the level of biochemical and
      haematological indicators in blood. The study demonstrated that an addition of Fe
      Gly to mixtures for broilers can be fully effective in terms of production and
      health performance even if the suggested requirement for this element is 50% or
      25% covered.

PMID- 25865672
TI  - Implantation of a cardiac resynchronization therapy defibrillator through a
      persistent left superior vena cava.

PMID- 25865673
TI  - Predicting Alcohol Pre-Drinking in Australian Undergraduate Students Using an
      Integrated Theoretical Model.
AB  - BACKGROUND: The aim of the present study was to examine the social-cognitive and
      motivational factors associated with pre-drinking based on a model integrating
      motivational constructs from self-determination theory and belief-based
      constructs from the theory of planned behaviour. METHODS: A prospective
      correlational design was used. Participants (N = 286; 66.4% female) completed
      self-report measures of past alcohol consumption, autonomous and controlled forms
      of motivation from self-determination theory, and attitudes, subjective norms,
      perceived behavioural control, and behavioural intentions from the theory of
      planned behaviour at baseline. Participants reported pre-drinking frequency four
      weeks later. RESULTS: Variance-based structural equation modelling showed that
      the hypothesised model predicted 54 per cent of the variance in pre-drinking
      intentions at baseline, and 20 per cent of the variance in pre-drinking behaviour
      at follow-up. Mediation analyses indicated strong, statistically significant
      effects of autonomous motivation on intentions to pre-drink, partially mediated
      by attitudes and subjective norms. Intention and perceived behavioural control
      significantly predicted pre-drinking frequency. CONCLUSIONS: Results provide
      support for the hypothesised model relationships. Autonomous motivation,
      attitude, subjective norm, and perceived behavioural control were influential in
      forming students' intentions to pre-drink. However, consistent with previous
      findings, the intention-behaviour relationship was relatively weak. Future
      research should look to non-intentional and volitional processes that may
      influence pre-drinking in undergraduates.

PMID- 25865674
TI  - A retrospective study of the prescribing and outcomes of tyrosine kinase
      inhibitors in chronic myeloid leukaemia over a period of more than 10 years.
AB  - WHAT IS KNOWN AND OBJECTIVE: Since their introduction, tyrosine kinase inhibitors
      (TKIs) have been increasingly used in clinical practice. We describe the
      prescribing and the clinical and biological consequences of two such inhibitors,
      imatinib and erlotinib, in patients with chronic myeloid leukaemia (CML) in a
      practice setting over a period of more than 10 years. METHODS: All patients who
      received at least one TKI for chronic phase CML between 2001 and 2012 in our
      university hospital were included in the study. RESULTS AND DISCUSSION: Of the
      139 patients, with a median age of 57 years, who were surveyed, imatinib and
      nilotinib were prescribed as the first TKI in 131 (94%) and 8 (6%) patients,
      respectively. With a median follow-up of 6 years, 342 treatment modifications
      were observed: 113 (33%) increased doses, 109 (32%) decreased doses, 89 (26%) TKI
      changes, 14 (4%) definitive discontinuations, 13 (4%) temporary discontinuations
      and 4 (1%) additions of IFN-alpha. The main reasons for the 342 treatment
      modifications were adverse events (n = 112, 33%), long-term optimal response (n =
      58, 17%) and failure (n = 57, 17%). Eighty-five (61%), 31 (22%), 18 (13%) and 5
      (4%) patients had no, 1, 2 and 3 TKI changes, respectively. Imatinib was the most
      prescribed TKI (75%). Adverse events resulting in treatment modifications
      occurred in 18% of patients for imatinib, 49% for nilotinib and 41% for dasatinib
      (P < 0.001). Median time to TKI change whatever the reason was >50 months (not
      achieved) for imatinib, 22 months for nilotinib and 27 months for dasatinib (log
      rank test, P < 0.001). WHAT IS NEW AND CONCLUSION: Imatinib was the most
      prescribed TKI both in the first and in subsequent therapeutic lines for chronic
      phase CML. Our study showed a very good efficacy-safety profile for imatinib at a
      median follow-up of 6 years in an unselected French population.

PMID- 25865675
TI  - Time-lapse imaging assay using the BioStation CT: a sensitive drug-screening
      method for three-dimensional cell culture.
AB  - Three-dimensional (3D) cell culture is beneficial for physiological studies of
      tumor cells, due to its potential to deliver a high quantity of cell culture
      information that is representative of the cancer microenvironment and predictive
      of drug responses in vivo. Currently, gel-associated or matrix-associated 3D cell
      culture is comprised of intricate procedures that often result in experimental
      complexity. Therefore, we developed an innovative anti-cancer drug sensitivity
      screening technique for 3D cell culture on NanoCulture Plates (NCP) by employing
      the imaging device BioStation CT. Here, we showed that the human breast cancer
      cell lines BT474 and T47D form multicellular spheroids on NCP plates and compared
      their sensitivity to the anti-cancer drugs trastuzumab and paclitaxel using the
      BioStation CT. The anticancer drugs reduced spheroid migration velocity and
      suppressed spheroid fusion. In addition, primary cells derived from the human
      breast cancer tissues B58 and B61 grown on NCP plates also exhibited similar drug
      sensitivity. These results were in good agreement with the conventional assay
      method using ATP quantification. We confirmed the antitumor effects of the drugs
      on cells seeded in 96-well plates using the BioStation CT imaging technique. We
      expect this method to be useful in research for new antitumor agents and for drug
      sensitivity tests in individually-tailored cancer treatments. 

PMID- 25865676
TI  - Safety and efficacy of splenic artery embolization for portal hyperperfusion in
      liver transplant recipients: A 5-year experience.

PMID- 25865678
TI  - The Cyclic Di-GMP Phosphodiesterase Gene Rv1357c/BCG1419c Affects BCG Pellicle
      Production and In Vivo Maintenance.
AB  - Bacteria living in a surface-attached community that contains a heterogeneous
      population, coated with an extracellular matrix, and showing drug tolerance
      (biofilms) are often linked to chronic infections. In mycobacteria, the pellicle
      mode of growth has been equated to an in vitro biofilm and meets several of the
      criteria mentioned above, while tuberculosis infection presents a chronic
      (latent) phase of infection. As mycobacteria lack most genes required to control
      biofilm production by other microorganisms, we deleted or expressed from the
      hsp60 strong promoter the only known c-di-GMP phosphodiesterase (PDE) gene in
      Mycobacterium bovis BCG. We found changes in pellicle production, cellular
      protein profiles, lipid production, resistance to nitrosative stress and
      maintenance in lungs and spleens of immunocompetent BALB/mice. Our results show
      that pellicle production and capacity to remain within the host are linked in
      BCG.

PMID- 25865677
TI  - Progress in the molecular understanding of central regulation of body weight by
      estrogens.
AB  - OBJECTIVE: Estrogens can act in the brain to prevent body weight gain. Tremendous
      research efforts have been focused on estrogen physiology in the brain in the
      context of body weight control; estrogen receptors and the related signals have
      been attractive targets for development of new obesity therapies. The objective
      is to review recent findings on these aspects. METHODS: Recent studies that used
      conventional and conditional knockout mouse strains to delineate the cellular and
      molecular mechanisms for the beneficial effects of estrogens on body weight
      balance are reviewed. Emerging genetic tools that could further benefit the field
      of estrogen research and a newly developed estrogen-based regimen that produces
      body weight-lowering benefits also are discussed. RESULTS: The body weight
      lowering effects of estrogens are mediated by multiple forms of estrogen
      receptors in different brain regions through distinct but coordinated mechanisms.
      Both rapid signals and "classic" nuclear receptor actions of estrogen receptors
      appear to contribute to estrogenic regulation of body weight. CONCLUSIONS:
      Estrogen receptors and associated signal networks are potential targets for
      obesity treatment, and further investigations are warranted.

PMID- 25865679
TI  - Flaxseed mitigates brain mass loss, improving motor hyperactivity and spatial
      memory, in a rodent model of neonatal hypoxic-ischemic encephalopathy.
AB  - Neonatal hypoxic-ischemic (HI) encephalopathy is a major cause of perinatal
      morbimortality. There is growing evidence that n-3 polyunsaturated fatty acids,
      especially docosahexaenoic acid (DHA), attenuate brain injury. This study aimed
      to investigate the possible neuroprotective effect of maternal intake of
      flaxseed, rich in DHA's precursor alpha-linolenic acid, in the young male
      offspring subjected to perinatal HI. Wistar rats were divided in six groups,
      according to maternal diet and offspring treatment at day 7: Control HI (CHI) and
      Flaxseed HI (FHI); Control Sham and Flaxseed Sham; Control Control and Flaxseed
      Control. Flaxseed diet increased offspring's hippocampal DHA content and lowered
      depressive behavior. CHI pups presented brain mass loss, motor hyperactivity and
      poor spatial memory, which were improved in FHI rats. Maternal flaxseed intake
      may prevent depressive symptoms in the offspring and promote neuroprotective
      effects, in the context of perinatal HI, improving brain injury and its cognitive
      and behavioral impairments. 

PMID- 25865680
TI  - The traditional drug Gongjin-Dan ameliorates chronic fatigue in a forced-stress
      mouse exercise model.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Gongjin-Dan is a representative traditional
      Oriental medicine herbal drug that has been used to treat chronic fatigue
      symptoms for several hundred years. We evaluated the anti-fatigue effects of
      Gongjin-Dan and the underlying mechanisms in a chronic forced exercise mouse
      model. METHODS AND MATERIALS: Balb/C male mice underwent an extreme treadmill
      based running stress (1-h, 5 days/week), and daily oral administration of
      distilled water, Gongjin-Dan (100, 200, or 400 mg/kg), or ascorbic acid (100
      mg/kg) for 28 days. The anti-fatigue effects of Gongjin-Dan were evaluated with
      behavioral tests (exercise tolerance and swimming tests), and the corresponding
      mechanisms were investigated based on oxidative stress and inflammatory cytokine
      and stress hormone levels in skeletal muscle, sera, and brain tissue. RESULTS:
      Gongjin-Dan significantly increased exercise tolerance and latency times but
      reduced the number of electric shocks and immobilization time on the treadmill
      running and swimming tests, compared with the control group. Gongjin-Dan also
      significantly ameliorated alterations in oxidative stress-related biomarkers
      (reactive oxygen species and malondialdehyde), inflammatory cytokines (tumor
      necrosis factor-alpha, interleukin-1 beta, interleukin-6, and interferon-gamma)
      and glycogen and L-lactate levels in skeletal muscle, compared with those in the
      control group. Moreover, Gongjin-Dan considerably normalized the forced running
      stress-induced changes in serum corticosterone and adrenaline levels, as well as
      brain serotonin level. These antioxidant and anti-stress effects of Gongjin-Dan
      were supported by the results of Western blotting (4-hydroxynonenal and heme
      oxygenase-1) and the gene expression levels (serotonin receptor and serotonin
      transporter). CONCLUSION: These results support the clinical relevance of Gongjin
      Dan regarding anti-chronic fatigue properties. The underlying mechanisms involve
      attenuation of oxidative and inflammatory reactions in muscle and regulation of
      the stress response through the hypothalmo-pituitary-adrenal axis.

PMID- 25865681
TI  - Chinese herbal medicine network and core treatments for allergic skin diseases:
      Implications from a nationwide database.
AB  - ETHNO-PHARMACOLOGICAL RELEVANCE: Chinese herbal medicine (CHM) is commonly used
      to treat skin diseases, but CHM prescription patterns are difficult to understand
      due to their complexity and inter-connections. This study aimed to demonstrate
      CHM core treatments and network for treatment of allergic skin diseases by
      analyzing a nationwide prescription database. MATERIALS AND METHODS: All CHM
      prescriptions made for atopic dermatitis (with age limitation <= 12 years) and
      urticaria for the entire year of 2011 were included. Association rule mining
      (ARM) combined with social network analysis (SNA) were used to analyze CHM
      prescriptions and explore the CHM prescription pattern and network. RESULTS: A
      total of 27,350 and 97,188 prescriptions for atopic dermatitis and urticaria,
      respectively, were analyzed. Xiao-Feng-San (XFS) was the most commonly used CHM
      (32% of prescriptions for atopic dermatitis and 47.4% for urticaria) and was the
      core treatment for both diseases. Moreover, 42 and 82 important CHM-CHM
      combinations were identified to establish the CHM network, and XFS with Dictamnus
      dasycarpus Turcz was the most prevalent (6.4% for atopic dermatitis and 9.1% for
      urticaria). Traditional Chinese Medicine heat syndrome was most prevalent cause.
      Extensive anti-inflammation, anti-allergy, anti-oxidation, and anti-bacterial
      effects were also found among the CHMs. CONCLUSIONS: Network analysis on CHM
      prescriptions provides graphic and comprehensive illustrations regarding CHM
      treatment for atopic dermatitis and urticaria. The CHM network analysis of
      prescriptions is essential to realize the CHM treatments and to select suitable
      candidates for clinical use or further studies.

PMID- 25865682
TI  - Glypican-3 as a specific biomarker for hepatocellular carcinoma.

PMID- 25865683
TI  - Progression-free survival as surrogate endpoint in advanced pancreatic cancer:
      meta-analysis of 30 randomized first-line trials.
AB  - BACKGROUND: Progression-free survival (PFS) has not been extensively investigated
      as a surrogate for survival in the first-line treatments of pancreatic cancer.
      The aim of this review was to evaluate PFS as a potential surrogate endpoint for
      overall survival (OS) in advanced pancreatic cancer in trials comparing poly
      chemotherapy to gemcitabine alone. DATA SOURCES: A systematic literature search
      in PubMed, Embase, Web of Science, and the Cochrane Central Register of
      Controlled Trials was conducted. The key words included randomized trial, first
      line chemotherapy, pancreatic cancer, gemcitabine and poly-chemotherapy. Adjusted
      weighted linear regression was used to calculate RS (Spearman's rank-order
      correlation coefficient) between PFS and post-progression survival (PPS) with OS
      (RS) and between treatment effects on PFS and OS (RHR). RESULTS: A total of 30
      trials including 8467 patients met the inclusion criteria. Correlation between
      the treatment effects on PFS and OS (RHR=0.78) and between the endpoint PFS and
      OS was high across all studies (RS=0.75). The slope of the regression line was
      0.76+/-0.26, indicating that an agent producing a 10% risk reduction for PFS will
      provide a 7.6%+/-2.6% risk reduction for OS. Correlation between PPS and OS was
      very strong (RS=0.71) and accounted for more than 50% of the whole OS variability
      (R2=0.57). CONCLUSION: Because of the robust correlation with OS and the
      potential influence of PPS caused by the second line therapies, it may be
      justified to consider PFS as a surrogate endpoint in trials evaluating new
      cytotoxic agents when gemcitabine is the control arm.

PMID- 25865684
TI  - Preoperative diabetes as a protective factor for pancreatic fistula after
      pancreaticoduodenectomy: a meta-analysis.
AB  - BACKGROUND: The role of diabetes mellitus (DM) in pancreatic fistula (PF) or
      clinical relevant PF (CR-PF) after pancreaticoduodenectomy (PD) or pylorus
      preserving pancreaticoduodenectomy (PPPD) is unclear. We conducted a meta
      analysis to investigate the relationship between DM and PF or CR-PF. DATA
      SOURCES: Embase, MEDLINE and Cochrane databases were searched systematically for
      relevant articles from January 2005 to June 2013. The selected studies that
      examined clinical risk factors of PF or CR-PF were included. We created pooled
      estimates for our outcomes using the random-effects model. RESULTS: Sixteen
      observational clinical studies were included. Pooling of PF rates from ten
      studies revealed that DM was associated with a decreased risk of PF (P=0.01). CR
      PF rates from 8 studies showed no significant difference between DM and control
      group (P=0.14). CONCLUSIONS: DM is not a risk factor for PF in patients
      undergoing PD or PPPD. On the contrary, patients without DM are at a higher risk
      of PF because the pancreases in these patients have more fatty tissue and the
      pancreas is soft.

PMID- 25865685
TI  - Beneficial mechanisms of aerobic exercise on hepatic lipid metabolism in non
      alcoholic fatty liver disease.
AB  - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) refers to any fatty liver
      disease that is not due to excessive use of alcohol. NAFLD probably results from
      abnormal hepatic lipid metabolism and insulin resistance. Aerobic exercise is
      shown to improve NAFLD. This review aimed to evaluate the molecular mechanisms
      involved in the beneficial effects of aerobic exercise on NAFLD. DATA SOURCE: We
      searched articles in English on the role of aerobic exercise in NAFLD therapy in
      PubMed. RESULTS: The mechanisms of chronic aerobic exercise in regulating the
      outcome of NAFLD include: (i) reducing intrahepatic fat content by down
      regulating sterol regulatory element-binding protein-1c and up-regulating
      peroxisome proliferator-activated receptor gamma expression levels; (ii)
      decreasing hepatic oxidative stress through modulating the reactive oxygen
      species, and enhancing antioxidant enzymes such as catalase and glutathione
      peroxidase; (iii) ameliorating hepatic inflammation via the inhibition of pro
      inflammatory mediators such as tumor necrosis factor-alpha and interleukin-1
      beta; (iv) attenuating mitochondrial dependent apoptosis by reducing cytochrome C
      released from the mitochondria to the cytosol; and (v) inducing hepato-protective
      autophagy. CONCLUSION: Aerobic exercise, via different mechanisms, significantly
      decreases the fat content of the liver and improves the outcomes of patients with
      NAFLD.

PMID- 25865686
TI  - Current strategies for preventing the recurrence of hepatocellular carcinoma
      after liver transplantation.
AB  - BACKGROUND: Liver transplantation is the optimal treatment for a selected group
      of patients with moderate to severe cirrhosis and hepatocellular carcinoma (HCC).
      Despite the strict selection of candidates, post-transplant recurrence often
      occurs and markedly reduces the long-term survival of patients with HCC. The
      present review focuses on the current strategies on preventing the recurrence of
      HCC after liver transplantation. DATA SOURCES: Relevant articles were identified
      by extensive searching of PubMed using the keywords "hepatocellular carcinoma",
      "recurrence" and "liver transplantation" between January 1996 and January 2014.
      Additional papers were searched manually from the references in key articles.
      RESULTS: The current theories of HCC recurrence after liver transplantation are:
      (i) the growth of pre-transplant occult metastases; (ii) the engraftment of
      circulating tumor cells released at the time of transplantation. Pre-transplant
      treatment aims to control local tumor by radiofrequency ablation, transarterial
      embolization and transarterial chemoembolization. The main objective during the
      operation is to prevent tumor cell dissemination. Post-transplant treatment
      includes systemic anticancer therapy, antiviral therapy, and most recently,
      immunotherapy. These strategies concentrate on the control of the tumor when the
      patients are waiting for transplant, to reduce the release of HCC cells during
      surgical procedures and to clear the occult HCC cells after transplantation.
      CONCLUSIONS: Much can be done to prevent HCC recurrence after liver
      transplantation. In future, effort is likely to be directed towards combining
      multidisciplinary approaches and various treatment modalities.

PMID- 25865687
TI  - Major complications of adult right lobe living liver donors.
AB  - BACKGROUND: The right lobe of the liver is generally preferred for living donor
      liver transplantation in adult patients with end-stage liver disease. It is
      important to know the preoperative factors relating to the major postoperative
      complications. We therefore evaluated the possible risk factors for predicting
      postoperative complications in right lobe liver donors. METHODS: Data from 378
      donors who had undergone right lobe hepatectomy at our center were evaluated
      retrospectively. The factors we evaluated included donor age, gender, body mass
      index (BMI), remnant liver volume, operation time, history of previous abdominal
      surgery, inclusion of the middle hepatic vein and variations in the portal and
      bile systems. RESULTS: Of the 378 donors, 219 were male and 159 female. None of
      the donors died, but 124 (32.8%) donors experienced complications including major
      complications (Clavien scores III and IV) in 27 (7.1%). Univariate analysis
      showed that complications were significantly associated with male gender and
      higher BMI (P<0.05), but not with donor age, remnant liver volume, operation
      time, graft with middle hepatic vein, variations in the portal and bile systems
      and previous abdominal surgery (P<0.05). Multivariate logistic regression
      analysis showed that major complications were significantly associated with male
      gender (P=0.005) and higher BMI (P=0.029). Moreover, the Chi-square test showed
      that there were significant relationships between major complications and male
      gender (P=0.010, X2=6.614, df=1) and BMI >25 kg/m2 (P=0.031, X2=8.562, df=1). Of
      the 96 male donors with BMI >25 kg/m2, 14 (14.6%) with major complications had
      significantly smaller mean remnant liver volume than those (82, 85.4%) without
      major complications (32.50%+/-4.45% vs 34.63%+/-3.11%, P=0.029). CONCLUSION: Male
      donors with BMI >25 kg/m2 and a remnant liver volume <=32.50% had a significantly
      increased risk for major complications.

PMID- 25865688
TI  - Prognostic value of glypican-3 in patients with HBV-associated hepatocellular
      carcinoma after liver transplantation.
AB  - BACKGROUND: Glypican-3 (GPC-3) is frequently overexpressed in hepatocellular
      carcinoma (HCC). Recent studies have shown that GPC-3 is a highly efficient
      diagnostic biomarker of HCC and an indicator of poor prognosis in HCC patients
      who have undergone hepatectomy. However, its prognostic value in patients with
      HBV-associated HCC after liver transplantation (LT) is not clear. The present
      study is to evaluate the prognostic value of GPC-3 in patients with HBV
      associated HCC after LT. METHODS: A cohort of 104 HCC patients with HBV
      associated cirrhosis who had undergone LT at our hospital between 2002 and 2011
      were enrolled in this study. Samples of HCC were taken from these patients. GPC-3
      protein expression was detected in paraffin-embedded specimens using
      immunohistochemistry. All related clinical data were obtained from the China
      Liver Transplant Registry. The relationship between GPC-3 expression and
      clinicopathological parameters was analyzed. Univariate and multivariate Cox
      regression analyses were used to identify risk factors for poor prognosis.
      RESULTS: GPC-3 was expressed in samples from 74 (71.2%) of the 104 patients. GPC
      3 was expressed only in HCC cells. Positive staining was correlated with tumor
      size (P=0.004), encapsulation (P=0.018), pathological stage (P=0.027), portal
      vein invasion (P=0.043), tumor differentiation (P=0.002) and the Milan criteria
      (P=0.016). The 5-year survival rate and disease-free survival rate of patients
      with GPC-3-positive were lower than those (38.2% vs 75.4%, P<0.001; 30.8% vs
      69.7%, P=0.001) of patients with GPC-3-negative. Multivariate Cox-regression
      analysis revealed that GPC-3 was an independent risk factor for 5-year survival
      rate (P=0.031) and disease-free survival rate (P=0.047), together with tumor
      differentiation, Milan criteria and pre-operative alpha-fetoprotein. CONCLUSION:
      GPC-3 is a potential biomarker for poor prognosis after LT in HCC patients with
      HBV-associated cirrhosis.

PMID- 25865689
TI  - sFRP-4, a potential novel serum marker for chronic hepatitis B-related
      hepatocellular carcinoma.
AB  - BACKGROUND: The current methods used for diagnosing hepatocellular carcinoma
      (HCC) are unsatisfactory. Here, we assessed the serum levels of secreted frizzled
      related protein 4 (sFRP-4) for diagnosing HCC in patients infected with chronic
      hepatitis B (CHB). METHODS: In 272 patients with CHB enrolled, 142 were patients
      with HCC. Thirty-three healthy subjects were recruited as healthy controls. The
      CHB patients were assigned to a test group or a validation group based on the
      time of enrollment. Human antibody arrays were used to screen 15 patients (8 CHB
      related HCC patients, 7 CHB patients) for serum markers. Four markers and one
      candidate marker were assessed in the test group and validation group,
      respectively. RESULTS: Human antibody assays indicated that the serum levels of
      sFRP-4 in HCC patients were significantly higher than those in CHB patients
      (P<0.05). Additionally, serum sFRP-4 levels were significantly higher in the HCC
      patients than those in the non-HCC patients in both test group (79.7 vs 41.3
      ng/mL; P<0.001) and validation group (89.0 vs 39.0 ng/mL; P<0.001). Areas under
      the Receiver Operating Characteristic curves (AUCs) for alpha-fetoprotein (AFP)
      and sFRP-4 were similar in both test group and validation group. In the test
      group, the combination of sFRP-4 (a sensitivity of 94.4%, a specificity of 60.5%
      at 46.4 ng/mL) and AFP (a sensitivity of 75.0%, a specificity of 87.2% at 11.3
      ng/mL) showed better performance for diagnosing HCC (a sensitivity of 79.2% and a
      specificity of 95.3%). The AUC for combined sFRP-4 and AFP increased to 0.941
      (95% CI: 0.908-0.975), and similar results were seen in the validation group.
      CONCLUSION: sFRP-4 is a candidate serum marker for diagnosing HCC in CHB
      patients, and the combination of sFRP-4 with AFP may improve the diagnostic
      accuracy of HCC.

PMID- 25865690
TI  - Expression of prothymosin alpha predicts early recurrence and poor prognosis of
      hepatocellular carcinoma.
AB  - BACKGROUND: Prothymosin alpha (PTMA) is a nuclear oncoprotein-transcription
      factor essential for cell cycle progression and proliferation. PTMA was
      overexpressed in several human malignancies including hepatocellular carcinoma
      (HCC). However, the prognostic significance of PTMA protein expression in HCC
      remains unclear. In the present study, we evaluated PTMA protein expression by
      immunohistochemistry in order to elucidate the prognostic roles of PTMA in HCC
      patients. METHODS: By immunohistochemistry, we investigated the expression of
      PTMA protein in tumor tissue from 226 HCC patients who underwent curative
      hepatectomy. Univariate and multivariate analyses were performed to evaluate its
      predictive value for tumor recurrence and survival of patients. The median follow
      up period was 120 months. RESULTS: PTMA expression was observed in 162 (71.7%) of
      the 226 HCC patients and was significantly associated with higher Edmondson
      grade, microvascular invasion, intrahepatic metastasis, higher American Joint
      Committee on Cancer (AJCC) T-stage, and lower albumin level. PTMA expression was
      an independent predictor of early recurrence (P=0.001). PTMA expression showed an
      unfavorable influence on recurrence-free survival (RFS) (P<0.001). Subgroup
      analysis showed that among patients with tumor size <=5.0 cm (140 patients),
      patients at AJCC T-stage 1 (95 patients) and patients with alpha-fetoprotein <=20
      ng/mL (83 patients), the differences in RFS between PTMA-positive and PTMA
      negative groups were also statistically significant (P=0.017, P=0.002 and
      P=0.002, respectively). In addition, PTMA expression was an independent predictor
      of shorter RFS (P=0.011). PTMA expression showed an unfavorable influence on
      overall survival (P=0.014), but was not an independent predictor of shorter
      overall survival (P=0.161). CONCLUSIONS: PTMA protein expression might be a novel
      predictor of early recurrence and RFS in HCC patients, even those at early stage
      or with alpha-fetoprotein-negative after curative hepatectomy. PTMA could be used
      as an immunohistochemical biomarker to detect patients with a high risk of
      recurrence.

PMID- 25865691
TI  - Preoperative serum liver enzyme markers for predicting early recurrence after
      curative resection of hepatocellular carcinoma.
AB  - BACKGROUND: Early recurrence of hepatocellular carcinoma (HCC) is associated with
      worse prognosis after liver resection. This study aimed to investigate the
      prognostic value of common liver enzyme markers in HCC early recurrence after
      curative hepatectomy and to establish a simple predictive model for HCC early
      recurrence. METHODS: A total of 200 patients who had undergone curative resection
      for HCC were retrospectively analyzed. The patients were divided into early
      recurrence (within 2 years) and non-early recurrence groups. Demographical
      characteristics, preoperative liver function parameters, surgical factors and
      tumor related factors of the patients were assessed by univariate analysis to
      identify potential significant predictors for early recurrence after resection of
      HCC. Parameters with statistical significance were entered into a Cox
      proportional hazard model to find independent risk factors. Receiver operating
      characteristic analysis was done to determine optimal cut-off values and the
      number of combined factors in multi-factor predictive model. RESULTS: Of 13
      potential risk factors for early recurrence identified by univariate analysis,
      high lactate dehydrogenase (LDH>206 U/L, HR=1.711, P=0.006), high aspartate
      aminotransferase (AST)/alanine aminotransferase (ALT) ratio (AST/ALT>0.96,
      HR=1.769, P=0.006), elevated alpha-fetoprotein (AFP<8.6 ng/mL, HR=2.079,
      P=0.007), small resection margin (<=1 cm, HR=2.354, P<0.001) and advanced TNM
      stage (TNM III-IV, HR=2.164, P<0.001) were independent risk factors for early
      recurrence of HCC shown by multivariate analysis. Patients with three or more
      concurrent independent risk factors had significantly higher risk for early
      recurrence than those with low risk factors. The sensitivity and specificity of
      this predictive model are 53.6% and 80.7%, respectively (area under curve=0.741,
      95% CI 0.674-0.800, P<0.0001). CONCLUSIONS: Preoperative common liver enzyme
      markers, LDH and AST/ALT ratio, were independently associated with early
      recurrence of HCC. The combination of serum liver enzyme markers with AFP,
      resection margin and TNM stage better predicted early recurrence of HCC after
      curative resection in a simple multi-factor model.

PMID- 25865692
TI  - Mesenchymal stem cells from the human umbilical cord ameliorate fulminant hepatic
      failure and increase survival in mice.
AB  - BACKGROUND: Cell therapy has been promising for various diseases. We investigated
      whether transplantation of human umbilical cord mesenchymal stem cells (hUCMSCs)
      has any therapeutic effects on D-galactosamine/lipopolysaccharide (GalN/LPS)
      induced fulminant hepatic failure in mice. METHODS: hUCMSCs isolated from human
      umbilical cord were cultured and transplanted via the tail vein into severe
      combined immune deficiency mice with GalN/LPS-induced fulminant hepatic failure.
      After transplantation, the localization and differentiation of hUCMSCs in the
      injured livers were investigated by immunohistochemical and genetic analyses. The
      recovery of the injured livers was evaluated histologically. The survival rate of
      experimental animals was analyzed by the Kaplan-Meier method and log-rank test.
      RESULTS: hUCMSCs expressed high levels of CD29, CD73, CD13, CD105 and CD90, but
      did not express CD31, CD79b, CD133, CD34, and CD45. Cultured hUCMSCs displayed
      adipogenic and osteogenic differentiation potential. Hematoxylin and eosin
      staining revealed that transplantation of hUCMSCs reduced hepatic necrosis and
      promoted liver regeneration. Transplantation of hUCMSCs prolonged the survival
      rate of mice with fulminant hepatic failure. Polymerase chain reaction for human
      alu sequences showed the presence of human cells in mouse livers. Positive
      staining for human albumin, human alpha-fetoprotein and human cytokeratin 18
      suggested the formation of hUCMSCs-derived hepatocyte-like cells in vivo.
      CONCLUSIONS: hUCMSC was a potential candidate for stem cell based therapies.
      After transplantation, hUCMSCs partially repaired hepatic damage induced by
      GalN/LPS in mice. hUCMSCs engrafted into the injured liver and differentiated
      into hepatocyte-like cells.

PMID- 25865693
TI  - Pentoxifylline enhances the protective effects of hypertonic saline solution on
      liver ischemia reperfusion injury through inhibition of oxidative stress.
AB  - BACKGROUND: Liver ischemia reperfusion (IR) injury triggers a systemic
      inflammatory response and is the main cause of organ dysfunction and adverse
      postoperative outcomes after liver surgery. Pentoxifylline (PTX) and hypertonic
      saline solution (HTS) have been identified to have beneficial effects against IR
      injury. This study aimed to investigate if the addition of PTX to HTS is superior
      to HTS alone for the prevention of liver IR injury. METHODS: Male Wistar rats
      were allocated into three groups. Control rats underwent 60 minutes of partial
      liver ischemia, HTS rats were treated with 0.4 mL/kg of intravenous 7.5% NaCl 15
      minutes before reperfusion, and HPTX group were treated with 7.5% NaCl plus 25
      mg/kg of PTX 15 minutes before reperfusion. Samples were collected after
      reperfusion for determination of ALT, AST, TNF-alpha, IL-6, IL-10, mitochondrial
      respiration, lipid peroxidation, pulmonary permeability and myeloperoxidase.
      RESULTS: HPTX significantly decreased TNF-alpha 30 minutes after reperfusion.
      HPTX and HTS significantly decreased ALT, AST, IL-6, mitochondrial dysfunction
      and pulmonary myeloperoxidase 4 hours after reperfusion. Compared with HTS only,
      HPTX significantly decreased hepatic oxidative stress 4 hours after reperfusion
      and pulmonary permeability 4 and 12 hours after reperfusion. CONCLUSION: This
      study showed that PTX added the beneficial effects of HTS on liver IR injury
      through decreases of hepatic oxidative stress and pulmonary permeability.

PMID- 25865694
TI  - Contrast-enhanced ultrasound in diagnosis of gallbladder adenoma.
AB  - BACKGROUND: Gallbladder adenoma is a pre-cancerous neoplasm and needs surgical
      resection. It is difficult to differentiate adenoma from other gallbladder polyps
      using imaging examinations. The study aimed to illustrate characteristics of
      contrast-enhanced ultrasound (CEUS) and its diagnostic value in gallbladder
      adenoma. METHODS: Thirty-seven patients with 39 gallbladder adenomatoid lesions
      (maximal diameter >=10 mm and without metastasis) were enrolled in this study.
      Lesion appearances in conventional ultrasound and CEUS were documented. The
      imaging features were compared individually among gallbladder cholesterol polyp,
      gallbladder adenoma and malignant lesion. RESULTS: Adenoma lesions showed iso
      echogenicity in ultrasound, and an eccentric enhancement pattern, "fast-in and
      synchronous-out" contrast enhancement pattern and homogeneous at peak-time
      enhancement in CEUS. The homogenicity at peak-time enhancement showed the highest
      diagnostic ability in differentiating gallbladder adenoma from cholesterol
      polyps. The sensitivity, specificity, positive predictive value, negative
      predictive value, accuracy and Youden index were 100%, 90.9%, 92.9%, 100%, 95.8%
      and 0.91, respectively. The characteristic of continuous gallbladder wall shown
      by CEUS had the highest diagnostic ability in differentiating adenoma from
      malignant lesion (100%, 86.7%, 86.7%, 100%, 92.9% and 0.87, respectively). The
      characteristic of the eccentric enhancement pattern had the highest diagnostic
      ability in differentiating adenoma from cholesterol polyp and malignant lesion,
      with corresponding indices of 69.2%, 88.5%, 75.0%, 85.2%, 82.1% and 0.58,
      respectively. CONCLUSIONS: CEUS is valuable in differentiating gallbladder
      adenoma from other gallbladder polyps (>=10 mm in diameter). Homogeneous
      echogenicity on peak-time enhancement, a continuous gallbladder wall, and the
      eccentric enhancement pattern are important indicators of gallbladder adenoma on
      CEUS.

PMID- 25865695
TI  - Mutations in the p16 gene in DMBA-induced pancreatic intraepithelial neoplasia
      and pancreatic cancer in rats.
AB  - BACKGROUND: 7, 12-dimethylbenzanthracene (DMBA)-induced pancreatic
      intraepithelial neoplasia (PanIN) and pancreatic cancer in rats provide a classic
      model for uncovering the molecular mechanisms underlying pancreatic cancer.
      However, this model has not been characterized genetically, and in particular,
      the major genetic alterations in the p16 gene are unknown. METHODS: Lesions of
      PanIN and pancreatic cancer were induced with DMBA implantation in 40 rats, and
      control pancreatic tissue was obtained from 10 age-matched rats without exposure
      to DMBA. Pancreatic tissue was harvested three months after DMBA implantation and
      DNA was extracted. Homozygous deletions and point mutations of the p16 (exons 1
      and 2) gene were detected by PCR amplification and direct sequencing. RESULTS:
      DMBA implantation in the 40 rats induced 26 PanINs and 9 carcinomas. The overall
      frequency of p16 alterations in the pancreatic tissue of these rats was 42.86%
      (15/35), and the changes were point mutations, not homozygous deletions. p16
      mutations were present in 30.77% (8/26) of the rats with PanIN and 77.78% (7/9)
      of the rats with carcinoma (P<0.05). The increasing incidence of p16 alterations
      was detected in 20.00% (1/5) of PanIN-1, 28.57% (2/7) of PanIN-2 and 35.71%
      (5/14) of PanIN-3 lesions. CONCLUSION: Our findings indicated that p16 alteration
      is a common event in the carcinogenesis of this model and that the mutation
      pattern is analogous to that of human lesions.

PMID- 25865696
TI  - Inhibition of pancreatic stellate cell activity by adipose-derived stem cells.
AB  - BACKGROUND: Pancreatic stellate cells (PSCs) play a critical role in the
      development of pancreatic fibrosis. In this study we used a novel method to
      isolate and culture rat PSCs and then investigated the inhibitory effects of
      adipose-derived stem cells (ADSCs) on activation and proliferation of PSCs.
      METHODS: Pancreatic tissue was obtained from Sprague-Dawley rats for PSCs
      isolation. Transwell cell cultures were adopted for co-culture of ADSCs and PSCs.
      PSCs proliferation and apoptosis were determined using CCK-8 and flow cytometry,
      respectively. alpha-SMA expressions were analyzed using Western blotting. The
      levels of cytokines [nerve growth factor (NGF), interleukin-10 (IL-10) and
      transforming growth factor-beta1 (TGF-beta1)] in conditioned medium were detected
      by ELISA. Gene expression (MMP-2, MMP-9 and TIMP-1) was analyzed using qRT-PCR.
      RESULTS: This method produced 17.6+/-6.5X10(3) cells per gram of the body weight
      with a purity of 90%-95% and a viability of 92%-97%. Co-culture of PSCs with
      ADSCs significantly inhibited PSCs proliferation and induced PSCs apoptosis.
      Moreover, alpha-SMA expression was significantly reduced in PSCs+ADSCs compared
      with that in PSC-only cultures, while expression of fibrinolytic proteins (e.g.,
      MMP-2 and MMP-9) was up-regulated and anti-fibrinolytic protein (TIMP-1) was down
      regulated. In addition, NGF expression was up-regulated, but IL-10 and TGF-beta1
      expressions were down-regulated in the co-culture conditioned medium compared
      with those in the PSC-only culture medium. CONCLUSIONS: This study provided an
      easy and reliable technique to isolate PSCs. The data demonstrated the inhibitory
      effects of ADSCs on the activation and proliferation of PSCs in vitro.

PMID- 25865697
TI  - Chiral habit selection on nanostructured epitaxial quartz films.
AB  - Understanding the crystallization of enantiomorphically pure systems can be
      relevant to diverse fields such as the study of the origins of life or the
      purification of racemates. Here we report on polycrystalline epitaxial thin films
      of quartz on Si substrates displaying two distinct types of chiral habits that
      never coexist in the same film. We combine Atomic Force Microscopy (AFM) analysis
      and computer-assisted crystallographic calculations to make a detailed study of
      these habits of quartz. By estimating the surface energies of the observed
      crystallites we argue that the films are enantiomorphically pure and we briefly
      outline a possible mechanism to explain the habit and chiral selection in this
      system. 

PMID- 25865698
TI  - Methylene Blue as a Photosensitizer and Redox Agent: Synthesis of 5-Hydroxy-1H
      pyrrol-2(5H)-ones from Furans.
AB  - A highly efficient and general singlet-oxygen-initiated one-pot transformation of
      readily accessible furans into 5-hydroxy-1H-pyrrol-2(5H)-ones has been developed.
      The methodology was extended to the synthesis of other high-value alpha,beta
      unsaturated gamma-lactams. This useful set of transformations relies not only on
      the photosensitizing ability of methylene blue, but also on its redox properties:
      properties that have until now been virtually ignored in a synthetic context. 

PMID- 25865699
TI  - At the Back of my Mind.

PMID- 25865700
TI  - Up-Regulation of miR-34a Expression in Response to the Luteolin-Induced Neurite
      Outgrowth of PC12 Cells.
AB  - Luteolin (3',4',5,7-tetrahydroxyflavone), a flavonoid found in several vegetables
      and fruits, has been reported to possess neurotrophic activities that are
      associated with its capacity to promote neuronal survival and differentiation. In
      the present study, we report for the first time a genomewide screen for microRNAs
      (miRNAs) regulated during the luteolin-mediated neurite outgrowth of PC12 cells.
      We found that after luteolin treatment, the abundance of 16 miRNAs was markedly
      up-regulated and that of 3 miRNAs was down-regulated in PC12 cells. The induction
      of miR-34a by luteolin was the most pronounced among these differentially
      expressed miRNAs. The correlation between miR-34a down-regulation and decreased
      luteolin-mediated neurite outgrowth may indicate a mechanism by which miR-34a may
      act as a modulator of neuronal differentiation. Furthermore, we found that
      luteolin enhanced the phosphorylation of p53 at Ser15, which was associated with
      the promotion of miR-34a transcription and neurite outgrowth. Moreover, the level
      of sirtuin 1 (SIRT1), a known miR-34a target, was reduced during luteolin-induced
      neurite outgrowth. In turn, the level of acetylated p53, a substrate of SIRT1,
      was correspondingly increased in luteolin-treated PC12 cells. In addition to p53
      activation, we further identified that luteolin-induced miR-34a transcription and
      neurite outgrowth involved the activation of the JNK and p38 MAPK pathways.
      However, the inhibition of JNK and p38 MAPK activation did not block luteolin
      induced p53 activation in PC12 cells. Our findings suggested that the activation
      of both p53-dependent and p53-independent miR-34a/SIRT1 pathways plays a critical
      role in the mechanisms underlying luteolin-induced neuritogenesis. 

PMID- 25865701
TI  - A call to action: reducing toxic stress during pregnancy and early childhood.

PMID- 25865702
TI  - The Effect of Art Therapy with Clay on Hopelessness Levels Among Neurology
      Patients.
AB  - PURPOSE: This study was performed to determine the effect of art therapy with
      clay on hopelessness levels of patients under treatment in departments of
      neurology. DESIGN: The study was of one group, pre- and posttest design. METHODS:
      This study was performed on patients who were hospitalized in the neurology
      departments of a university and a state hospital between February and May 2012 in
      Turkey. The sample for the study comprised 50 neurology patients with diagnoses
      of epilepsy (17 patients) and stroke (33 patients). The patients in the study
      were asked to create objects of clay of any shape they desired. Data for the
      research were collected with a sociodemographic data form and by using the Beck
      Hopelessness Scale (BHS). FINDINGS: While BHS scores of neurology patients before
      clay therapy were found higher compared to the scores after therapy with clay,
      there was also a statistically significant difference. After clay therapy, BHS
      scores were lower in women, in married patients, in patients who suffered from a
      stroke, people who had chronic disease, people without psychological illness, and
      in the case of children. CONCLUSION: The study showed that clay therapy had an
      impact on the hopelessness levels of neurology patients. CLINICAL RELEVANCE: Art
      therapy with clay may be used for rehabilitation purposes in neurology patients,
      both in the hospital and at home after discharge.

PMID- 25865703
TI  - Fast eQTL Analysis for Twin Studies.
AB  - Twin data are commonly used for studying complex psychiatric disorders, and mixed
      effects models are one of the most popular tools for modeling dependence
      structures between twin pairs. However, for eQTL (expression quantitative trait
      loci) data where associations between thousands of transcripts and millions of
      single nucleotide polymorphisms need to be tested, mixed effects models are
      computationally inefficient and often impractical. In this paper, we propose a
      fast eQTL analysis approach for twin eQTL data where we randomly split twin pairs
      into two groups, so that within each group the samples are unrelated, and we then
      apply a multiple linear regression analysis separately to each group. A score
      statistic that automatically adjusts the (hidden) correlation between the two
      groups is constructed for combining the results from the two groups. The proposed
      method has well-controlled type I error. Compared to mixed effects models, the
      proposed method has similar power but drastically improved computational
      efficiency. We demonstrate the computational advantage of the proposed method via
      extensive simulations. The proposed method is also applied to a large twin eQTL
      data from the Netherlands Twin Register. 

PMID- 25865704
TI  - The influence of poly(ethylene glycol) on the micelle formation of alkyl
      maltosides used in membrane protein crystallization.
AB  - With the aim of better understanding the phase behavior of alkyl maltosides (n
      alkyl-beta-d-maltosides, CnG2) under the conditions of membrane protein
      crystallization, we studied the influence of poly(ethylene glycol) (PEG) 2000, a
      commonly used precipitating agent, on the critical micelle concentration (CMC) of
      the alkyl maltosides by systematic variation of the number n of carbon atoms in
      the alkyl chain (n = 10, 11, and 12) and the concentration of PEG2000 (chi) in a
      buffer suitable for the crystallization of cyanobacterial photosystem II. CMC
      measurements were based on established fluorescence techniques using pyrene and 8
      anilinonaphthalene-1-sulfonate (ANS). We found an increase of the CMC with
      increasing PEG concentration according to ln(CMC/CMC0) = kPchi, where CMC0 is the
      CMC in the absence of PEG and kP is a constant that we termed the "polymer
      constant". In parallel, we measured the influence of PEG2000 on the surface
      tension of detergent-free buffer solutions. At PEG concentrations chi > 1% w/v,
      the surface pressure pis(chi) = gamma(0) - gamma(chi) was found to depend
      linearly on the PEG concentration according to pis(chi) = kappachi + pis(0),
      where gamma(0) is the surface tension in the absence of PEG. Based on a molecular
      thermodynamic modeling, CMC shifts and surface pressure due to PEG are related,
      and it is shown that kP = kappac(n) + eta, where c(n) is a detergent-specific
      constant depending inter alia on the alkyl chain length n and eta is a correction
      for molarity. Thus, knowledge of the surface pressure in the absence of a
      detergent allows for the prediction of the CMC shift. The PEG effect on the CMC
      is discussed concerning its molecular origin and its implications for membrane
      protein solubilization and crystallization. 

PMID- 25865705
TI  - Exogenous arachidonic acid mediates permeability of human brain microvessel
      endothelial cells through prostaglandin E2 activation of EP3 and EP4 receptors.
AB  - The blood-brain barrier, formed by microvessel endothelial cells, is the
      restrictive barrier between the brain parenchyma and the circulating blood.
      Arachidonic acid (ARA; 5,8,11,14-cis-eicosatetraenoic acid) is a conditionally
      essential polyunsaturated fatty acid [20:4(n-6)] and is a major constituent of
      brain lipids. The current study examined the transport processes for ARA in
      confluent monolayers of human brain microvascular endothelial cells (HBMEC).
      Addition of radioactive ARA to the apical compartment of HBMEC cultured on
      Transwell((r)) inserts resulted in rapid incorporation of radioactivity into the
      basolateral medium. Knock down of fatty acid transport proteins did not alter ARA
      passage into the basolateral medium as a result of the rapid generation of
      prostaglandin E2 (PGE2 ), an eicosanoid known to facilitate opening of the blood
      brain barrier. Permeability following ARA or PGE2 exposure was confirmed by an
      increased movement of fluorescein-labeled dextran from apical to basolateral
      medium. ARA-mediated permeability was attenuated by specific cyclooxygenase-2
      inhibitors. EP3 and EP4 receptor antagonists attenuated the ARA-mediated
      permeability of HBMEC. The results indicate that ARA increases permeability of
      HBMEC monolayers likely via increased production of PGE2 which acts upon EP3 and
      EP4 receptors to mediate permeability. These observations may explain the rapid
      influx of ARA into the brain previously observed upon plasma infusion with ARA.
      The blood-brain barrier, formed by microvessel endothelial cells, is a
      restrictive barrier between the brain parenchyma and the circulating blood.
      Radiolabeled arachidonic acid (ARA) movement across, and monolayer permeability
      in the presence of ARA, was examined in confluent monolayers of primary human
      brain microvessel endothelial cells (HBMECs) cultured on Transwell((r)) plates.
      Incubation of HBMECs with ARA resulted in a rapid increase in HBMEC monolayer
      permeability. The mechanism was mediated, in part, through increased
      prostaglandin E2 production from ARA which acted upon EP3 and EP4 receptors to
      increase HBMEC monolayer permeability.

PMID- 25865706
TI  - Molecular assessment of differences in the duodenal microbiome in subjects with
      irritable bowel syndrome.
AB  - OBJECTIVE: Breath testing and duodenal culture studies suggest that a significant
      proportion of irritable bowel syndrome (IBS) patients have small intestinal
      bacterial overgrowth. In this study, we extended these data through 16S rDNA
      amplicon sequencing and quantitative PCR (qPCR) analyses of duodenal aspirates
      from a large cohort of IBS, non-IBS and control subjects. MATERIALS AND METHODS:
      Consecutive subjects presenting for esophagogastroduodenoscopy only and healthy
      controls were recruited. Exclusion criteria included recent antibiotic or
      probiotic use. Following extensive medical work-up, patients were evaluated for
      symptoms of IBS. DNAs were isolated from duodenal aspirates obtained during
      endoscopy. Microbial populations in a subset of IBS subjects and controls were
      compared by 16S profiling. Duodenal microbes were then quantitated in the entire
      cohort by qPCR and the results compared with quantitative live culture data.
      RESULTS: A total of 258 subjects were recruited (21 healthy, 163 non-healthy non
      IBS, and 74 IBS). 16S profiling in five IBS and five control subjects revealed
      significantly lower microbial diversity in the duodenum in IBS, with significant
      alterations in 12 genera (false discovery rate < 0.15), including
      overrepresentation of Escherichia/Shigella (p = 0.005) and Aeromonas (p = 0.051)
      and underrepresentation of Acinetobacter (p = 0.024), Citrobacter (p = 0.031) and
      Microvirgula (p = 0.036). qPCR in all 258 subjects confirmed greater levels of
      Escherichia coli in IBS and also revealed increases in Klebsiella spp, which
      correlated strongly with quantitative culture data. CONCLUSIONS: 16S rDNA
      sequencing confirms microbial overgrowth in the small bowel in IBS, with a
      concomitant reduction in diversity. qPCR supports alterations in specific
      microbial populations in IBS.

PMID- 25865707
TI  - Brain gray and white matter differences in healthy normal weight and obese
      children.
AB  - PURPOSE: To compare brain gray and white matter development in healthy normal
      weight and obese children. METHODS: Twenty-four healthy 8- to 10-year-old
      children whose body mass index was either <75(th) percentile (normal weight) or
      >95(th) percentile (obese) completed an MRI examination which included T1
      weighted three-dimensional structural imaging and diffusion tensor imaging (DTI).
      Voxel-based morphometry was used to compare the regional gray and white matter
      between the normal weight and obese children, and tract-based spatial statistics
      was used to compare the water diffusion parameters in the white matter between
      groups. RESULTS: Compared with normal weight children, obese children had
      significant (P < 0.05, family wise error corrected) regional gray matter
      reduction in the right middle temporal gyrus, left and right thalami, left
      superior parietal gyrus, left pre/postcentral gyri, and left cerebellum. Obese
      children also had higher white matter (P < 0.05, corrected) in multiple regions
      in the brain and higher DTI measured fractional anisotropy (FA) values (P < 0.05,
      corrected) in part of the left brain association and projection fibers. There was
      no difference in mean diffusivity at P < 0.05, corrected. DTI eigenvalues
      suggested that the FA differences were likely from decreased radial diffusivity
      (P < 0.1, corrected) and there was no change in axial diffusivity (corrected P >
      0.35 for all voxels). CONCLUSION: Our results indicated that obese but otherwise
      healthy children have different regional gray and white matter development in the
      brain and differences in white matter microstructures compared with healthy
      normal weight children.

PMID- 25865708
TI  - Behavioral and endocrine evaluation of the stressfulness of single-pen housing
      compared to group-housing and social isolation conditions.
AB  - Regulation of neuroendocrine responses is often studied in animals housed indoors
      in individual contiguous pens. In sheep, these housing conditions are used to
      control the environment, facilitate biological sampling and limit social stress.
      However, this type of housing also prevents exploratory behaviors and could
      induce stereotypies, non-compliant with welfare and possibly associated with a
      state of stress. In this context, we investigated the impact of housing in a
      single-pen, with other familiar conspecifics, on emotional state by evaluating
      behavioral, hormonal and neuronal measures in adult ewes. We hypothesized that
      emotional state would be more negative in animals housed in a single-pen for one
      week (Pen) than in freely moving animals (Free) but less negative than in
      socially isolated subjects (Isol). We tested our hypothesis in ovariectomized
      ewes to avoid the interaction with sexual steroid variations. Our behavioral,
      endocrine and neuronal (Fos activation of the corticotropin-releasing hormone
      neurons in the paraventricular nucleus of the hypothalamus) measures confirmed
      that withdrawing familiar conspecifics was sufficient to induce strong stress
      responses in Isol ewes, but there was no indication that Pen ewes were stressed.
      However, the latter showed less mastication activity than Free ewes, probably due
      to limited accessibility to straw. The highest plasma prolactin levels were
      observed in Isol and Free animals, which might result from stress and physical
      activity, respectively. In Free ewes, plasma dopamine was low, consistent with
      its inhibitory control of prolactin. However, Isol animals had both high levels
      of prolactin and dopamine, suggesting a dysregulated balance in socially stressed
      ewes. As in other species, we suggest that the regulation of prolactin by
      dopamine varies with stress and/or social context. Overall, this study shows that
      the impact of housing conditions on different neuroendocrine systems should be
      considered more in the future. 

PMID- 25865709
TI  - Can perceptual indices estimate physiological strain across a range of
      environments and metabolic workloads when wearing explosive ordnance disposal and
      chemical protective clothing?
AB  - OBJECTIVE: Explosive ordnance disposal (EOD) often requires technicians to wear
      multiple protective garments in challenging environmental conditions. The
      accumulative effect of increased metabolic cost coupled with decreased heat
      dissipation associated with these garments predisposes technicians to high levels
      of physiological strain. It has been proposed that a perceptual strain index
      (PeSI) using subjective ratings of thermal sensation and perceived exertion as
      surrogate measures of core body temperature and heart rate, may provide an
      accurate estimation of physiological strain. Therefore, this study aimed to
      determine if the PeSI could estimate the physiological strain index (PSI) across
      a range of metabolic workloads and environments while wearing heavy EOD and
      chemical protective clothing. METHODS: Eleven healthy males wore an EOD and
      chemical protective ensemble while walking on a treadmill at 2.5, 4 and 5.5km.h(
      1) at 1% grade in environmental conditions equivalent to wet bulb globe
      temperature (WBGT) 21, 30 and 37 degrees C. WBGT conditions were randomly
      presented and a maximum of three randomised treadmill walking trials were
      completed in a single testing day. Trials were ceased at a maximum of 60-min or
      until the attainment of termination criteria. A Pearson's correlation
      coefficient, mixed linear model, absolute agreement and receiver operating
      characteristic (ROC) curves were used to determine the relationship between the
      PeSI and PSI. RESULTS: A significant moderate relationship between the PeSI and
      the PSI was observed [r=0.77; p<0.001; mean difference=0.8+/-1.1a.u. (modified
      95% limits of agreement -1.3 to 3.0)]. The ROC curves indicated that the PeSI had
      a good predictive power when used with two, single-threshold cut-offs to
      differentiate between low and high levels of physiological strain (area under
      curve: PSI three cut-off=0.936 and seven cut-off=0.841). CONCLUSIONS: These
      findings support the use of the PeSI for monitoring physiological strain while
      wearing EOD and chemical protective clothing. However, future research is needed
      to confirm the validity of the PeSI for active EOD technicians operating in the
      field.

PMID- 25865710
TI  - Cryopreservation of Piau-Breed Wild Boar Sperm: Assessment of Cooling Curves and
      Centrifugation Regimes.
AB  - This study aimed to assess the effects of different cooling curves and
      centrifugation regimes used in cryopreservation protocols on the post-thaw
      viability of Piau-breed wild boar (Sus scrofa) sperm using in vitro assessment
      tests. Two centrifugations (800 g for 10 min and 2400 g for 3 min) and two
      cooling curves (conventional cooling using nitrogen vapour - freezing 1 and
      automated cooling using a programmed freezing machine - freezing 2) were tested.
      Therefore, the treatments were divided into M3 - centrifugation at 2400 g for 3
      min and freezing 2; M10 - centrifugation at 800 g for 10 min and freezing 2; R3 -
      centrifugation at 2400 g for 3 min and freezing 1; and R10 - centrifugation at
      800 g for 10 min and freezing 1. No significant differences (p > 0.05) between
      treatments occurred post-thawing regarding the total sperm motility means
      recorded. The mean values of the different treatments were not different from
      each other regarding the supravital staining (SV), hypo-osmotic test (HO), sperm
      egg binding assay or sperm morphology. This study showed that both the cooling
      curve and the centrifugation regime affected the quality of post-thaw sperm, and
      centrifugation for shorter times and cooling curves using automated cooling are
      the most suitable for minimizing sperm injury. 

PMID- 25865711
TI  - Mass-transport-controlled, large-area, uniform deposition of carbon nanofibers
      and their application in gas diffusion layers of fuel cells.
AB  - The effect of mass transport on the growth characteristics of large-area vapor
      grown carbon nanofibers (CNFs) was investigated by adjusting the substrate
      deposition angle (alpha). The catalyst precursor solution was coated onto one
      side of a 2D porous carbon paper substrate via a decal printing method. The
      results showed that the CNFs were grown on only one side of the substrate and
      alpha was found to significantly affect the growth uniformity. At alpha = 0
      degrees , the growth thickness, the density, the microstructure and the yield of
      the CNF film were uniform across the substrate surface, whereas the growth
      uniformity decreased with increasing alpha, suggesting that the large-area CNF
      deposition processes were mass-transport-controlled. Computational fluid dynamics
      simulations of the gas diffusion processes revealed the homogeneous distributions
      of the carbon-source-gas concentration, pressure, and velocity near the substrate
      surface at alpha = 0 degrees , which were the important factors in achieving the
      mass-transport-limited uniform CNF growth. The homogeneity of the field
      distributions decreased with increasing alpha, in accordance with the variation
      in the growth uniformity with alpha. When used as a micro-porous layer, the
      uniform CNF film enabled higher proton exchange membrane fuel cell performance in
      comparison with commercial carbon black by virtue of its improved electronic and
      mass-transport properties confirmed by the electrochemical impedance spectroscopy
      results. 

PMID- 25865712
TI  - Neonatal Coronoid Hyperplasia: A Report of a Case and Concepts to Promote Early
      Diagnosis and Treatment.
AB  - Limited mouth opening in the neonatal patient is primarily caused by either soft
      tissue or hard tissue pathologic features. Differentiation between the two can
      usually be elicited by physical examination with the patient under anesthesia.
      Limited opening from soft tissue pathologic features can be increased with
      stretching. In contrast, osseous pathologic features will produce an anatomic
      stop. Syndromic cases with hard tissue pathologic features are primarily due to
      coronoid hyperplasia. Our aims are to help clinicians evaluate and identify
      mandibular hypomobility in the pediatric patient resulting from coronoid
      hyperplasia and to promote early treatment to improve long-term oral function. We
      present the case of a 2-month-old male who was born premature at 30 weeks by
      emergency cesarean section. Examination revealed multiple anomalies, including
      significant trismus with a maximal opening of 4 mm. A computed tomography scan
      revealed significant bilateral coronoid hyperplasia. At the age of 90 days, the
      patient underwent bilateral coronoidectomies with endoscopic guidance under
      general anesthesia. After resection, the patient was able to open his mouth to 25
      mm. This opening was maintained with postoperative physiotherapy. Clinical
      problems can arise from the potential sequelae of neonatal trismus. Acutely,
      these problems can range from feeding difficulty and potential malnutrition to
      aspiration and emergent airway compromise. Long-term consequences include growth
      restrictions because of malnutrition, speech delay, muscle contracture and
      atrophy, facial asymmetry, and the risk of infection owing to poor oral hygiene.
      Information is limited about neonatal treatment of condylar hyperplasia in the
      published data. Treatment tends to be delayed owing to a late diagnosis and
      referral, and patients are prone to developing relapse. Postoperative physical
      therapy will help to prevent relapse and allows for maintenance of the improved
      jaw range of motion. 

PMID- 25865713
TI  - How Can Paresthesia After Zygomaticomaxillary Complex Fracture Be Determined
      After Long-Term Follow-Up? A New and Quantitative Evaluation Method Using Current
      Perception Threshold Testing.
AB  - PURPOSE: The aims of the present study were to analyze the effectiveness of
      current perception threshold (CPT) testing to determine patients' minor
      paresthesia of the infraorbital region after open reduction and internal fixation
      (ORIF) for unilateral zygomaticomaxillary bone fracture (UZF) and to clarify
      which nerve fiber was related to the paresthesia. MATERIALS AND METHODS: We
      conducted a retrospective cohort study of patients who had undergone ORIF after
      UZF. We also performed neurosensory testing for healthy volunteers who served as
      the control group. The predictor variables were the period of measurement of
      Semmes-Weinstein monofilament (S-W) testing and CPT testing (preoperatively and 1
      and 5 years postoperatively), measurement side, and disease status (UZF or
      control). The outcome variables were paresthesia status of the infraorbital nerve
      region and the results of S-W and CPT testing in both UZF and control groups. The
      differences in the S-W and CPT values between the affected and unaffected sides
      in the UZF group and between the UZF and control groups were analyzed by t test
      (P < .05 was considered significant). RESULTS: The present study included 10
      patients (6 males and 4 females), with an average age of 25.0 +/- 12.7 years, and
      21 controls (10 males and 11 females), with an average age of 24.3 +/- 1.7 years.
      In the control group, the CPT and S-W test results did not show any significant
      differences between the left and right sides. All 10 patients had paresthesia at
      1 and 5 years postoperatively. At 5 years postoperatively, the S-W values in all
      patients showed normalization. From the results of CPT testing, only the A-beta
      fiber function showed significant improvement at 5 years postoperatively.
      CONCLUSION: The CPT test was an effective sensory test for determining minor
      paresthesia that could not be detected using S-W testing. Paresthesia of the
      infraorbital nerve region was caused by the damaged A-delta and C fibers.

PMID- 25865714
TI  - Lingual Nerve Repair: To Graft or Not to Graft?
AB  - PURPOSE: Since no studies have compared direct and graft repair of the lingual
      nerve, we examined the subjective and objective outcomes of lingual nerve repair
      by direct epineurial repair and indirect graft repair, assessed the effect of
      other confounding variables, and compared the outcomes of autograft and allograft
      repairs. PATIENTS AND METHODS: All patients who had undergone microneurosurgical
      repair of the lingual nerve from 2000 to 2012 by 1 surgeon (M.M.) were asked to
      complete an online questionnaire regarding their current neurosensory status at
      least 2 years after nerve repair. A direct comparison was made between patients
      who had undergone direct epineurial repair and those who had undergone
      interpositional nerve graft repair. Student's t test and chi(2) test were used to
      determine whether a significant difference existed in the success between the 2
      techniques and whether age, gender, race, delay from injury to repair, or degree
      of initial nerve deficit influenced the success of nerve repair. RESULTS: Of the
      72 patients identified, 43, who had undergone 47 nerve repairs (18 direct, 29
      indirect graft repairs [4 bilateral]; 28 female and 19 male patients; mean age
      28.3 years), were interviewed. The objective results of functional sensory
      recovery, defined by a Medical Research Council Scale grade of S3, S3+, or S4,
      was 89% for the graft repairs and 85% for the direct repairs (P = .01). The
      subjective patient satisfaction score (0 to 10 scale) was 8.9 for the graft
      repairs and 8.1 for the direct repairs (P = .02). The autograft and allograft
      repairs performed comparably, and the other variables (ie, age, gender, race,
      delay from injury to nerve repair, gap length, and initial Sunderland grade
      injury) were not found to be significant (P > .05). CONCLUSION: Graft repair of
      the lingual nerve provides superior long-term (>2 years) objective and subjective
      outcomes compared with direct repair. This might be because of the lack of
      tension at the repair site, more freedom with nerve stump preparation, and the
      addition of neurotropic and neurotrophic factors from the donor nerve graft at
      the site of injury to augment neurosensory recovery.

PMID- 25865715
TI  - Reply: To PMID 25579011.

PMID- 25865716
TI  - Outcomes of Primary Squamous Cell Carcinoma of Major Salivary Glands Treated by
      Surgery With or Without Postoperative Radiotherapy.
AB  - PURPOSE: To discuss the outcomes of primary squamous cell carcinoma (SCC) of the
      major salivary glands treated by surgery with or without postoperative adjuvant
      radiotherapy. MATERIALS AND METHODS: We performed a retrospective analysis of 579
      cases with malignancy originating in the major salivary glands. A total of 34
      cases were eligible for the present study. The outcomes were analyzed in terms of
      disease failure patterns and survival rates between the 2 treatment groups.
      RESULTS: The treatment was surgery alone in 16 patients and a combination of
      surgery and postoperative adjuvant radiotherapy in 18. The locoregional
      recurrence rate was 43.8% in the surgery group and 22.2% in the surgery plus
      radiotherapy group. The distant metastasis rate was 6.3% in the surgery group and
      44.4% in the surgery plus radiotherapy group. The 5-year disease-specific
      survival and disease-free survival (DFS) rate for all patients was 50.3% and
      35.3%, respectively. The 5-year disease-specific survival rate was 48.9% in the
      surgery group and 48.2% in the surgery plus radiotherapy group. The 5-year DFS
      rate was 25.0% in the surgery group and 31.2% in the surgery plus radiotherapy
      group. The log-rank test showed no significant differences in the disease
      specific survival or DFS rates between the 2 groups (P = .724 for disease
      specific survival and P = .269 for DFS). CONCLUSION: Planned postoperative
      adjuvant radiotherapy is anticipated to be able to improve locoregional control
      rates and DFS for patients with primary SCC of the major salivary glands.

PMID- 25865718
TI  - Maxillofacial Gunshot Injuries at an Urban Level I Trauma Center-10-Year
      Analysis.
AB  - PURPOSE: To analyze the current trends in the presentation and surgical treatment
      of patients admitted with facial gunshot wounds (GSWs) at an urban level 1 trauma
      center. MATERIALS AND METHODS: Retrospective analysis of facial GSWs treated by
      the Department of Oral and Maxillofacial Surgery at Boston Medical Center from
      2001 to 2011. The data were obtained from the institutional trauma registry and
      hospital records and analyzed with respect to the length of hospitalization,
      patient demographic data, treatment cost, and payments. RESULTS: During the study
      period, a total of 1,957 patients were admitted to the hospital with GSWs. Of
      these patients, 136 (6.9%) had injuries involving the facial region, 87% were
      men, and the most common injury was to neck zone III. Mandible fractures were
      encountered in 47% of the patients. The fractures were treated within 72 hours
      from admission for most patients; 22% of the patients required secondary surgical
      procedures, 20% of the patients had associated neurologic injuries, and 9% had
      cervical spine fractures. Angiography was performed in 60% of the patients, with
      13% requiring embolization. Finally, 70% of the patients required airway
      management, and the overall patient mortality was 9%. CONCLUSION: Airway
      compromise was the most common life-threatening early problem. Patients admitted
      with higher stages of shock and lower mental status because of brain, vascular,
      and/or spinal cord injuries experienced prolonged hospitalization, increased
      treatment costs, and extended rehabilitation. Most of the facial GSWs presented
      as non-life-threatening injuries, but typically resulted in significant
      morbidity. The vast majority of injured patients relied on public aid or had no
      insurance.

PMID- 25865717
TI  - Assessment of the OsteoMark-Navigation System for Oral and Maxillofacial Surgery.
AB  - PURPOSE: To assess the accuracy of a novel navigation system for maxillofacial
      surgery using human cadavers and a live minipig model. MATERIALS AND METHODS: We
      tested an electromagnetic tracking system (OsteoMark-Navigation) that uses simple
      sensors to determine the position and orientation of a hand-held pencil-like
      marking device. The device can translate 3-dimensional computed tomographic data
      intraoperatively to allow the surgeon to localize and draw a proposed osteotomy
      or the resection margins of a tumor on bone. The accuracy of the OsteoMark
      Navigation system in locating and marking osteotomies and screw positions in
      human cadaver heads was assessed. In group 1 (n = 3, 6 sides), OsteoMark
      Navigation marked osteotomies and screw positions were compared to virtual
      treatment plans. In group 2 (n = 3, 6 sides), marked osteotomies and screw
      positions for distraction osteogenesis devices were compared with those performed
      using fabricated guide stents. Three metrics were used to document the precision
      and accuracy. In group 3 (n = 1), the system was tested in a standard operating
      room environment. RESULTS: For group 1, the mean error between the points was 0.7
      mm (horizontal) and 1.7 mm (vertical). Compared with the posterior and inferior
      mandibular border, the mean error was 1.2 and 1.7 mm, respectively. For group 2,
      the mean discrepancy between the points marked using the OsteoMark-Navigation
      system and the surgical guides was 1.9 mm (range 0 to 4.1). The system maintained
      accuracy on a live minipig in a standard operating room environment. CONCLUSION:
      Based on this research OsteoMark-Navigation is a potentially powerful tool for
      clinical use in maxillofacial surgery. It has accuracy and precision comparable
      to that of existing clinical applications.

PMID- 25865719
TI  - Patients With Transmandibular Implants Are at Risk for Severe Complications When
      Becoming Frail.
AB  - Early in the implant era, transmandibular implant systems were used for retention
      of implant-retained mandibular overdentures in the severely resorbed mandible.
      These transmandibular systems require very thorough aftercare, especially when
      patients become frail and dependent on care. As a result, oral care often
      receives less attention in frail elderly patients or the patient cannot maintain
      the needed level of oral care. Care providers often are unfamiliar with the level
      of oral care needed to preserve transmandibular implants in good condition. This
      case series describes the risk for severe complications, including chronic pain
      and fracture of the mandible, in frail elderly patients who were unable to
      maintain oral care at the desired level and whose caregivers did not provide the
      needed level of oral care. 

PMID- 25865720
TI  - Stability of Modified Maxillomandibular Advancement Surgery in a Patient With
      Preadolescent Refractory Obstructive Sleep Apnea.
AB  - Maxillomandibular advancement (MMA) surgery can be considered a primary single
      stage treatment for improving the quality of life in patients with preadolescent
      refractory obstructive sleep apnea (OSA). The aim of the present report was to
      evaluate the treatment efficacy and stability of modified MMA surgery in a
      growing patient with morbidly severe symptoms and medical complications. Using
      the follow-up results from the questionnaire, polysomnography, 2-dimensional
      cephalometry, and 3-dimensional cone-beam computed tomography measurements, the
      success of modified MMA surgery was assessed in terms of the postoperative
      improvements of functions and esthetics and postretentive stability of the
      improvements throughout the growth period. The present report provides some
      clinical recommendations when considering skeletal surgery in preadolescent
      patients with OSA: 1) the decision criteria of MMA surgery as definite treatment;
      2) the proper surgical design for both maximum enlargement of the airway and
      esthetic improvement; and 3) the postoperative facial growth for long-term
      stability of airway function and skeletal improvement. With a systematic
      multidisciplinary approach, early surgical intervention can be used to treat OSA
      in children successfully and permanently. 

PMID- 25865721
TI  - Sexual coercion and adolescent risk behaviour: a systematic literature review.
AB  - Sexual coercion affects the individual through multiple short- and long-term
      medical, emotional, psychological and social consequences, and adolescents are
      particularly at high risk. Sexual coercion is hypothesised to negatively affect
      adolescents' decision-making around their sexual behaviours and other risk
      behaviours. Yet there is no previous systematic literature review on the topic to
      summarise current knowledge. The aim of this systematic literature review is to
      summarise previous research among adolescents investigating the associations
      between sexual coercion and risk behaviours, to critically appraise validity of
      the associations found, and to promote further research on the topic. Published
      articles were obtained by searching databases using specific keywords. Only 22
      articles were found to fit the inclusion criteria. The evidence substantiates the
      hypothesised associations between sexual coercion and later risk behaviours (e.g.
      multiple sexual partners, condom non-use, and pregnancy). It also presents
      differences between genders. However, the influences on behavioural outcomes are
      multifaceted and largely impacted by bias. There is a need for improved quality
      of studies-specifically an increased number of longitudinal and experimental
      design studies-and a clearer understanding of mediators and confounders.
      Furthermore, emphasis should be placed on addressing the consequences of sexual
      coercion and promoting interventions that reduce the extent of sexual coercion.
      This will have added benefit in terms of reducing risk behaviours. 

PMID- 25865722
TI  - Is assessing participation in daily activities a suitable approach for measuring
      the impact of disease on child development in African children?
AB  - INTRODUCTION: The Participation in Activities of Daily Living (PADL) instrument
      was developed out of a need for a culturally appropriate tool to measure the
      impact of ill health on children's well-being. OBJECTIVE: We sought to devise a
      psychometrically sound instrument to measure well-being through participation in
      daily activities for rural school-age children in Kenya. METHOD: The study was
      carried out at the Kenya Medical Research Institute/Centre for Geographic
      Medicine Research-Coast, in the Kilifi district of Coast Province. The process
      that was followed ensured an integration of community reported activity, use of a
      relevant vocabulary and a careful translation of concepts in the adaptation of an
      instrument used in other contexts. The reliability, validity and sensitivity of
      the PADL were evaluated in studies with clinical and community samples. RESULTS:
      Factor analysis suggested five potential summary scores measuring levels of
      participation and attitude to participation (alphas 0.56-0.91). Variability in
      children's responses on participation was significantly associated with ill
      health and level of schooling. CONCLUSION: The format and content of the
      questionnaire items concerning participation in activities of daily living were
      appropriate for use with rural children. The precise nature of the activities
      needs to be determined in context, taking into account both the nature of the
      health experience and the expected structure of a child's day.

PMID- 25865723
TI  - Where the streets have no names: factors associated with the provision of
      counselling and social work services for child rape survivors in KwaZulu-Natal,
      South Africa.
AB  - OBJECTIVE: The aim of this study was to audit the provision of state-assisted
      counselling and social work services to child rape survivors presenting for
      medico-legal assessment at a state hospital in KwaZulu- Natal, South Africa.
      METHOD: A prospective design was used to collect data from the social and medical
      case files of 200 consecutive cases of child rape referred for medico-legal
      assessment to a state hospital located to the north of the City of Durban (South
      Africa). For each case, information was obtained regarding survivor and offender
      demographics, the nature and duration of abuse, and the extent and nature of
      counselling and social work services provided. RESULTS: Only 49% of survivors
      benefited from state-supported counselling and social work services, with the
      provision of such services being frequently delayed (by periods of up to six
      months), and with service provision being restricted to a single intake interview
      in all but one case. Social work service provision was significantly less likely
      in cases where the survivor resided in an informal dwelling (OR = 0.507) and
      where the child presented for medico-legal assessment outside of normal working
      hours (OR = 0.625). From observations made during the study, it would appear that
      patterns of professional collaboration in relation to service provision for child
      rape survivors falls somewhat short of the ideal of effective multi-sectoral
      engagement. CONCLUSIONS: Levels of service provision observed in the study are
      unacceptably low, with there being a clear need for the development and
      implementation of carefully considered multi-sectoral protocols which are
      designed to effectively meet the needs of all child rape survivors.

PMID- 25865724
TI  - Teachers' perspectives of mental health needs in Nigerian schools.
AB  - OBJECTIVE: This study assessed teachers' perspectives on children's mental health
      needs and the development of school-based mental health programmes in South-West
      Nigeria. METHOD: Focus group discussions were held with teachers from randomly
      selected urban and rural primary schools in Ibadan, Nigeria. Data were analysed
      using interpretative phenomenological analysis. RESULTS: Teachers identified
      significant mental health problems in school-age children and described a variety
      of bio-psychosocial contributing factors. These ranged from problems with primary
      support systems to poverty, spiritual factors, medical illnesses and genetic
      vulnerability. The school environment was recognised as an ideal place for
      dealing with child mental health issues despite deficiencies in teachers'
      knowledge, skills and resources. A school mental health programme that would
      provide training for teachers and awareness campaigns as well as human, material
      and financial resources was proposed. CONCLUSIONS: The findings from this study
      provide a background for understanding the current state of interventions to
      address child mental health problems in a resource poor country in sub- Saharan
      Africa and specific areas where future program development is most likely to have
      an impact.

PMID- 25865725
TI  - The diagnosis and treatment of delirium in children.
AB  - Delirium is commonly encountered in the setting of paediatric consultation
      liaison psychiatry. However, it is commonly misdiagnosed as current operational
      diagnostic criteria may be difficult to apply in children. We present a practical
      approach to eliciting the signs and symptoms of delirium in children and a
      proposed treatment algorithm which elaborates a variety of environmental
      management strategies and includes explicit thresholds for the use of
      antipsychotic medications. 

PMID- 25865726
TI  - An adolescent's subjective experiences of mindfulness.
AB  - An adolescent's subjective experiences of mindfulness were explored in a single
      case study of a 17-year-old female. Data were created by means of 'mindfulness
      sessions', unstructured interviews, creative expression, journals and field
      notes. The data were analysed and interpreted using a combination of typological
      and interpretive analysis strategies. Findings are presented within a conceptual
      framework of mindfulness derived by the main author from the literature review.
      Five themes emerged from the data in relation to the conceptual framework
      applied, namely present-centered awareness and attention, attitude and heart
      qualities, self-regulation, universalism and mindlessness. Overall findings
      suggest firstly that the participant subjectively experienced mindfulness as
      being predominantly task-oriented. Secondly, it appears that the participant
      experienced personal growth and development in terms of her understanding and
      practice of mindfulness. These findings could make a potential contribution
      towards qualitative research on mindfulness, and research on how mindfulness
      could possibly apply to an adolescent. Studies have shown mindfulness to be a
      potentially promising intervention and quality to be cultivated in the
      development of well-being. The study is thus significant in the context of
      positive psychology and a move towards more holistic health and well-being. 

PMID- 25865727
TI  - The handbook of play therapy and therapeutic play.
AB  - 2009 (Second Edition), Routledge, London 281 pages, 2 tables, 6 figures
      Paperback, ISBN 978-0-415-43942-8, ZAR1 262.95. 

PMID- 25865728
TI  - Pathways to change: brief therapy with difficult adolescents.
AB  - 2005 (Second Edition), Guilford Press, 75 Spring Street, New York, NY 10012, USA
      Paperback, ISBN 978-1-59385-979-4 Hardback, ISBN 978-1-57230-959-3 ZAR 570
      (hardback). 

PMID- 25865729
TI  - Do dual forensic and therapy roles damage children?

PMID- 25865730
TI  - Journal abstracts from current research in the field of child and adolescent
      mental health.
AB  - Debate RD, Kelley PG, Zwald M, Huberty J & Zhang Y (2009) Changes in psychosocial
      factors and physical activity frequency among third- to eighth-grade girls who
      participated in a developmentally focused youth sport program: A preliminary
      study. Journal of School Health 79(10): 474-484 Boyce JC, Mueller NB, Hogan-Watts
      M & Luke Douglas A (2009) Evaluating the strength of school tobacco policies: The
      development of a practical rating system. Journal of School Health 79(10): 495
      504 Craine JL, Tanaka Teri A, Nishina A & Conger KJ (2009) Understanding
      adolescent delinquency: The role of older siblings' delinquency and popularity
      with peers. Merrill-Palmer Quarterly 55(4): 436-453 Rosales FJ, Reznick JS &
      Zeisel SH (2009) Understanding the role of nutrition in the rain and behavioural
      development of toddlers and pre-school children: Identifying methodological
      barriers. Nutritional Neuroscience 12(5): 190-202 Clemmens DA (2009) The
      Significance of motherhood for adolescents whose mothers have breast cancer.
      Oncology Nursing Forum 36(5): 571-577 Archambault I, Janosz M, Morizot J & Pagani
      L (2009) Adolescent behavioural, affective, and cognitive engagement in school:
      Relationship to dropout. Journal of School Health 79(9): 408-415 Denison JA,
      McCauley AP, Dunnett-Dagg WA, Lungu N & Sweat MD (2009) HIV testing among
      adolescents in Ndola, Zambia: How individual, relational, and environmental
      factors relate to demand. AIDS Education & Prevention 21(4): 314-324 Pollock JA &
      Halkitis PN (2009) Environmental factors in relation to unprotected sexual
      behaviour among gay, bisexual and other MSM. AIDS Education & Prevention 21(4):
      340-355 Nippold MA, Mansfield TC, Billow JL & Tomblin JB (2009) Syntactic
      development in adolescents with a history of language impairments: A follow-up
      investigation. American Journal of Speech-Language Pathology 18(3): 241-251
      Sharaf AY, Thompson EA & Walsh E (2009) Protective effects of self-esteem and
      family support on suicide risk behaviours among at-risk adolescents. Journal of
      Child & Adolescent Psychiatric Nursing 22(3): 160-168 Page RM & Hall CP (2009)
      Psychosocial distress and alcohol use as factors in adolescent sexual behaviour
      among sub-Saharan African adolescents. Journal of School Health 79(8): 369-379
      Taliaferro LA, Rienzo BA, Pigg RM, Miller MD & Dodd VJ (2009) Spiritual well
      being and suicidal ideation among college students. Journal of American College
      Health 58(1): 83-90 Jarrett T, Horn K & Zhang J (2009) Teen perceptions of
      facilitator characteristics in a school-based smoking cessation program. Journal
      of School Health 79(7): 297-303 Parker JS & Morton TL (2009) Distinguishing
      between early and late onset delinquents: Race, income, verbal intelligence and
      impulsivity. North American Journal of Psychology 11(2): 273-284 Burris JL, Smith
      GT & Carlson CR (2009) Relations among religiousness, spirituality and sexual
      practices. Journal of Sex Research 46(4): 282-289 Brown DW, Riley L, Butchart A,
      Meddings DR, Kann L & Harvey AP (2009) Exposure to physical and sexual violence
      and adverse health behaviours in African children: Results from the Global School
      based Student Health Survey. Bulletin of the World Health Organization 87(6): 447
      B. 

PMID- 25865732
TI  - Unifying psyche and soma for child healthcare in Africa.

PMID- 25865731
TI  - The South African Children's Act.

PMID- 25865734
TI  - A Subgroup Analysis Found no Diminished Response to Buprenorphine Transdermal
      System Treatment for Chronic Low Back Pain Patients Classified with Depression.
AB  - BACKGROUND: Chronic pain (CP) patients with depression typically exhibit worse
      post-treatment outcomes than nondepressed CP patients. The cause is often assumed
      to reflect a differential response to treatment, neglecting other potential
      explanations, such as the continuation of differences in pretreatment outcomes.
      This post hoc analysis examines whether worse post-treatment outcomes for
      depressed patients with chronic low back pain (CLBP) are driven by reduced
      treatment efficacy. METHODS: Data were from opioid-naive adult patients with
      moderate-to-severe CLBP who participated in a randomized, placebo-controlled,
      double-blind clinical trial of Butrans((r)) (buprenorphine) Transdermal System
      (BTDS) for pain relief. Depression screening was based on baseline SF-36v2 Mental
      Health subscale scores. Patient-reported measures of pain severity, pain
      interference, quality of life, sleep problems, and functional disability were
      administered at screening and during the study. Differential treatment efficacy
      for each outcome was examined using analysis of covariance models that included
      interaction terms between treatment arm and depression status. RESULTS: At
      baseline, patients classified as depressed showed greater pain interference,
      lower quality of life, more sleep problems, and greater functional disability
      than nondepressed patients; the two groups did not differ in pain severity. No
      statistically significant interactions between treatment arm and depression
      status were observed. The direction of improvement post-treatment favored the
      depressed group on nine of seventeen outcomes. CONCLUSIONS: Results do not
      support a differential response to BTDS treatment between depressed and
      nondepressed CLBP patients across a variety of patient-reported outcomes. These
      findings raise the question of whether depressed mood actually moderates the
      effectiveness of treatment in CP patients.

PMID- 25865735
TI  - Design, synthesis and initial characterisation of a radiolabelled
      [(18)F]pyrimidoindolone probe for detecting activated caspase-3/7.
AB  - Evasion of apoptosis is one of the six initially proposed hallmarks of cancer,
      and as such, a method to detect apoptosis in a tumour would be of considerable
      interest in both clinical trials of new cancer therapeutics, as well as for
      routine patient management. Activation of caspase-3/7 is a key biomarker of
      cellular apoptosis. Herein we describe the design, synthesis and initial
      characterisation of the first pyrimidoindolone compound for detection of caspase
      3/7 activation using positron emission tomography. 

PMID- 25865736
TI  - Biosynthesis of nectrisine in Thelonectria discophora SANK 18292.
AB  - Nectrisine, an iminosugar with a heterocyclic nitrogen-containing 5-membered
      ring, acts as a glycosidase inhibitor. Thelonectria discophora SANK 18292, a
      fungus, was identified as a nectrisine producer from its microbial library in our
      screening for nectrisine producing microorganisms. Biosynthesis of nectrisine
      produced by the fungus was studied using stable isotope tracer techniques.
      Incorporation of (13)C-labeled d-ribose and d-xylose into nectrisine was
      confirmed by mass spectrometry and (13)C NMR spectroscopy, which suggested that
      these were its precursors. Chromatographic separation of the hot water extract
      from the culture broth afforded not only nectrisine, but also substantial amounts
      of 4-amino-4-deoxyarabinitol. Incubation of the latter with the crude enzyme of
      the fungus at room temp. caused an increase in levels of nectrisine together with
      a decrease in amounts of the administered potential precursor suggesting that it
      is a biosynthetic intermediate. From these results, a biosynthetic pathway to
      nectrisine is proposed via d-xylulose 5-phosphate and 4-amino-4-deoxyarabinitol
      by the pentose phosphate pathway. 

PMID- 25865737
TI  - Sequence heterogeneity of cannabidiolic- and tetrahydrocannabinolic acid-synthase
      in Cannabis sativa L. and its relationship with chemical phenotype.
AB  - Sequence variants of THCA- and CBDA-synthases were isolated from different
      Cannabis sativa L. strains expressing various wild-type and mutant chemical
      phenotypes (chemotypes). Expressed and complete sequences were obtained from
      mature inflorescences. Each strain was shown to have a different specificity
      and/or ability to convert the precursor CBGA into CBDA and/or THCA type products.
      The comparison of the expressed sequences led to the identification of different
      mutations, all of them due to SNPs. These SNPs were found to relate to the
      cannabinoid composition of the inflorescence at maturity and are therefore
      proposed to have a functional significance. The amount of variation was found to
      be higher within the CBDAS sequence family than in the THCAS family, suggesting a
      more recent evolution of THCA-forming enzymes from the CBDAS group. We therefore
      consider CBDAS as the ancestral type of these synthases. 

PMID- 25865738
TI  - Active current gating in electrically biased conical nanopores.
AB  - We observed that the ionic current through a gold/silicon nitride (Si3N4)
      nanopore could be modulated and gated by electrically biasing the gold layer.
      Rather than employing chemical modification to alter device behavior, we achieved
      control of conductance directly by electrically biasing the gold portion of the
      nanopore. By stepping through a range of bias potentials under a constant trans
      pore electric field, we observed a gating phenomenon in the trans-pore current
      response in a variety of solutions including potassium chloride (KCl), sodium
      chloride (NaCl), and potassium iodide (KI). A computational model with a conical
      nanopore was developed to examine the effect of the Gouy-Chapman-Stern electrical
      double layer along with nanopore geometry, work function potentials, and applied
      electrical bias on the ionic current. The numerical results indicated that the
      observed modulation and gating behavior was due to dynamic reorganization of the
      electrical double layer in response to changes in the electrical bias.
      Specifically, in the conducting state, the nanopore conductance (both numerical
      and experimental) is linearly proportional to the applied bias due to
      accumulation of charge in the diffuse layer. The gating effect occurs due to the
      asymmetric charge distribution in the fluid induced by the distribution of
      potentials at the nanopore surface. Time dependent changes in current due to
      restructuring of the electrical double layer occur when the electrostatic bias is
      instantaneously changed. The nanopore device demonstrates direct external control
      over nanopore behavior via modulation of the electrical double layer by
      electrostatic biasing. 

PMID- 25865739
TI  - The complete chloroplast genome sequence of Clematis terniflora DC.
      (Ranunculaceae).
AB  - Clematis terniflora DC. is an important medicinal plant used in the treatment of
      inflammatory symptoms related to respiratory and urinary systems. In this study,
      we found that the complete cp genome of C. terniflora DC. is 159,528 bp. The
      phylogenetic analysis of 32 taxa showed a strong sister relationship with
      Ranunculus macranthus, which also strongly supports the position of Ranunculales.
      The complete cp genome sequence of Clematis terniflora DC. reported here has the
      potential to advance population and phylogenetic studies of this medicinal plant.

PMID- 25865740
TI  - Audiovisual preconditioning enhances the efficacy of an anatomical dissection
      course: A randomised study.
AB  - The benefits of incorporating audiovisual materials into learning are well
      recognised. The outcome of integrating such a modality in to anatomical education
      has not been reported previously. The aim of this randomised study was to
      determine whether audiovisual preconditioning is a useful adjunct to learning at
      an upper limb dissection course. Prior to instruction participants completed a
      standardised pre course multiple-choice questionnaire (MCQ). The intervention
      group was subsequently shown a video with a pre-recorded commentary. Following
      initial dissection, both groups completed a second MCQ. The final MCQ was
      completed at the conclusion of the course. Statistical analysis confirmed a
      significant improvement in the performance in both groups over the duration of
      the three MCQs. The intervention group significantly outperformed their control
      group counterparts immediately following audiovisual preconditioning and in the
      post course MCQ. Audiovisual preconditioning is a practical and effective tool
      that should be incorporated in to future course curricula to optimise learning.
      Level of evidence This study appraises an intervention in medical education.
      LEVEL OF EVIDENCE: Kirkpatrick Level 2b (modification of knowledge).

PMID- 25865741
TI  - HIV-1 prevalence and subtype/recombinant distribution among travelers entering
      China from Vietnam at the HeKou port in the Yunnan province, China, between 2003
      and 2012.
AB  - The aim of this study was to assess HIV-1 prevalence and the distribution of HIV
      1 subtypes among travelers crossing the border at the HeKou land port. Between
      2003 and 2012, 22,799 persons were randomly recruited from people entering China
      from Vietnam. In this crossing border population, a total of 161 (0.71%)
      travelers were determined as HIV-1-positive. From them, 140 HIV-1-positive serum
      samples were collected for RNA extraction and subsequent RT-nested PCR
      amplification of the group-specific antigen (gag)-RT with a length of 2.6 kb. The
      DNA sequences were analyzed to determine the HIV-1 subtypes/recombinants. We
      found that the circulating recombinant form 01_AE (CRF01_AE) was the most common
      HIV-1 subtype, accounting for 49.4% (41/83) of the subtyped 83 samples, followed
      by CRF08_BC (26.5%, 22/83) and CRF07_BC (7.2%, 6/83). Only 1 sample was
      classified as subtype C. Thirteen cases could not be clustered into any known
      subtypes or CRFs and presented as unique recombinant forms (URFs). Of them, 6
      recombination patterns were identified. They had distinct structures consisting
      of fragments of subtypes B, C, CRF01_AE, CRF07_BC and CRF08_BC. Between 2003 and
      2012, CRF01_AE and CRE08_BC were shown to be the most prevalent recombinant forms
      identified each year. But yearly change of each subtype is uncertain regular
      among in these travelers during the past decade. Understanding the distribution
      of HIV-1 subtypes/recombinants and how it changes across time among individuals
      entering China from Vietnam through this land port is crucial to establish
      strategies for the prevention of HIV cross-border transmission.

PMID- 25865742
TI  - An economic analysis of trial of labor after cesarean delivery.
AB  - OBJECTIVE: Given that cesarean delivery is one of the most commonly performed
      surgical procedures in the United States and an important contributor to
      obstetric care costs, this analysis sought to examine maternal hospital costs
      associated with trial of labor after cesarean delivery (TOLAC) versus repeat
      cesarean delivery (RCD). METHODS: A national sample was used to identify women
      with singleton pregnancy who underwent either TOLAC or RCD from 2006 to 2012.
      Women with diagnoses that could confound cost via extended hospital length of
      stay prior to delivery were excluded. Other medical and obstetric covariates that
      could influence cost were included in an adjusted model. RESULTS: A total of
      485,247 women were identified, including 365,596 (75.3%) cesarean deliveries
      without labor, 41,988 (8.6%) successful and 77,663 (16.0%) unsuccessful TOLAC
      deliveries. The inflation-adjusted median costs in this cohort were $5512 for
      cesarean without labor, $4175 for successful TOLAC, $5166 for all TOLAC attempts,
      and $5759 for failed TOLAC. In a multivariable model, hospital region was a major
      predictor of median cost as were demographic variables and medical comorbidities.
      CONCLUSION: TOLAC is associated with modest reductions of cost for maternal
      hospitalizations. However, other medical, demographic and hospital factors appear
      to be more important factors.

PMID- 25865743
TI  - Sustained activation of GABAA receptors in the suprachiasmatic nucleus mediates
      light-induced phase delays of the circadian clock: a novel function of ionotropic
      receptors.
AB  - The suprachiasmatic nucleus (SCN) contains a circadian clock that generates
      endogenous rhythmicity and entrains that rhythmicity with the day-night cycle.
      The neurochemical events that transduce photic input within the SCN and mediate
      entrainment by resetting the molecular clock have yet to be defined. Because GABA
      is contained in nearly all SCN neurons we tested the hypothesis that GABA serves
      as this signal in studies employing Syrian hamsters (Mesocricetus auratus).
      Activation of GABAA receptors was found to be necessary and sufficient for light
      to induce phase delays of the clock. Remarkably, the sustained activation of
      GABAA receptors for more than three consecutive hours was necessary to phase
      delay the clock. The duration of GABAA receptor activation required to induce
      phase delays would not have been predicted by either the prevalent theory of
      circadian entrainment or by expectations regarding the duration of ionotropic
      receptor activation necessary to produce functional responses. Taken together,
      these data identify a novel neurochemical mechanism essential for phase-delaying
      the 'master' circadian clock within the SCN as well as identifying an
      unprecedented action of an amino acid neurotransmitter involving the sustained
      activation of ionotropic receptors. 

PMID- 25865744
TI  - Cebranopadol : a first-in-class potent analgesic agent with agonistic activity at
      nociceptin/orphanin FQ and opioid receptors.
AB  - INTRODUCTION: Pain is a syndrome of various clinical disorders, which arises from
      various pathological conditions and which presents significant challenges in both
      its diagnosis and treatment. There is currently a strong medical demand to
      develop new therapies with a higher efficacy and a better tolerability profile.
      AREAS COVERED: In this review, the authors report on the available data for the
      pharmacological properties of cebranopadol (GRT6005), a first in-class, potent
      analgesic compound which acts as an agonist of nociceptin/orphanin FQ peptide
      (NOP) and opioid receptors. They highlight the in vitro receptor binding studies,
      as well as the in vivo preclinical results on the analgesic efficacy of
      cebranopadol obtained in several rodent pain models. The authors also briefly
      summarize the available data from clinical trials with cebranopadol. EXPERT
      OPINION: Cebranopadol displays analgesic, antiallodynic and antihyperalgesic
      properties in several rat models of acute nociceptive, inflammatory, cancer and
      neuropathic pain. In contrast to classical opioids, it has a higher analgesic
      potency in models of neuropathic pain than in acute nociceptive pain. Even at
      higher analgesic doses, cebranopadol does not induce motor coordination deficits
      or respiratory depression in rats. Hence, it seems to possess a broader
      therapeutic window than classical opioids. While it is particularly interesting
      as a novel, potent bifunctional agonist of NOP/opioid receptors, the outcome of
      its ongoing and planned clinical trials will be crucial for its future
      development and potential application in humans.

PMID- 25865745
TI  - Extracorporeal methods of blood glutamate scavenging: a novel therapeutic
      modality.
AB  - Pathologically elevated glutamate concentrations in the brain's extracellular
      fluid are associated with several acute and chronic brain insults. Studies have
      demonstrated that by decreasing the concentration of glutamate in the blood,
      thereby increasing the concentration gradient between the brain and the blood,
      the rate of brain-to-blood glutamate efflux can be increased. Blood glutamate
      scavengers, pyruvate and oxaloacetate have shown great promise in providing
      neuroprotection in many animal models of acute brain insults. However, glutamate
      scavengers' potential systemic toxicity, side effects and pharmacokinetic
      properties may limit their use in clinical practice. In contrast, extracorporeal
      methods of blood glutamate reduction, in which glutamate is filtered from the
      blood and eliminated, may be an advantageous adjunct in treating acute brain
      insults. Here, we review the current evidence for the glutamate-lowering effects
      of hemodialysis, peritoneal dialysis and hemofiltration. The evidence reviewed
      here highlights the need for clinical trials.

PMID- 25865746
TI  - Person-centered Climate Questionnaire-Patient in English: A psychometric
      evaluation study in long-term care settings.
AB  - BACKGROUND: There is increasing evidence that person-centered care improves
      nursing home residents' quality of life. Despite the clear focus of person
      centered care on enhancing care for residents and engaging residents in care,
      there are few options available for measuring person-centered care from the
      perspective of the elder residents. OBJECTIVE: The aim of this study was to
      assess the psychometric properties of the English version of the Person-centered
      Climate Questionnaire-Patient (PCQ-P) in U.S. long-term care settings. METHODS: A
      total of 189 older adults from six nursing homes in the Midwestern United States
      were included. Convergent validity and known-group comparison were examined for
      construct validity. Exploratory factor analysis and second-order confirmatory
      factor analysis were utilized to examine the factor structure. Reliability was
      tested using Cronbach's alpha values for internal consistency. RESULTS: This
      study demonstrated a substantial convergent validity of the PCQ-P in English as
      higher scores correlated significantly with higher resident life satisfaction
      (r=0.459), and the satisfactory construct validity as evidenced by a
      significantly higher mean PCQ-P score from residents in higher quality nursing
      homes. Factor analysis demonstrated that the PCQ-P had three factors
      (hospitality, safety, and everydayness) in U.S. nursing home residents. The PCQ-P
      showed satisfactory internal consistency reliability (alpha=0.89). CONCLUSION:
      The English version of the PCQ-P is a valid and reliable tool to directly measure
      the perceptions of the person-centered climate in the U.S nursing homes. The
      simple and straightforward PCQ-P items are easy to administer to nursing home
      residents. Consequently, clinical staff can utilize the PCQ-P to assess the unit
      climate, and evaluate outcomes of person-centered interventions.

PMID- 25865747
TI  - Serum autotaxin is independently associated with hepatic steatosis in women with
      severe obesity.
AB  - OBJECTIVE: Autotaxin (ATX) is an adipocyte-derived lysophospholipase that
      generates the lipid signaling molecule lysophosphatidic acid (LPA). The aim of
      this study was to determine the relationship between serum ATX and nonalcoholic
      fatty liver disease (NAFLD) in females with obesity. METHODS: 101 nondiabetic
      women with obesity (age: 31.5-55.8 years; BMI: 35.0-64.5 kg/m2) were classified
      as having NAFLD (36.3%) or not having NAFLD (63.7%) based on the degree of
      hepatic steatosis on abdominal CT. Subjects were characterized for metabolic
      phenotype including measures of energy, glucose, and lipid homeostasis. Fasting
      serum adipokines and inflammatory markers were determined by ELISA. Linear
      regression analysis was used to determine features independently associated with
      NAFLD. RESULTS: Subjects with and without NAFLD differed in several key features
      of metabolic phenotype including BMI, waist circumference, fasting glucose and
      insulin, HOMA-IR, VLDL, triglycerides, and ALT. Serum adipokines, including ATX
      and leptin, were higher in subjects with NAFLD. Serum ATX was significantly
      correlated with alkaline phosphatase, fasting glucose, fasting insulin, and HOMA
      IR. Linear regression analysis revealed that serum triglycerides and log
      transformed ATX were independently associated with hepatic steatosis.
      CONCLUSIONS: Serum ATX may be a potential pathogenic factor and/or biomarker for
      NAFLD in nondiabetic women with obesity.

PMID- 25865748
TI  - Bed sharing is more common in sudden infant death syndrome than in explained
      sudden unexpected deaths in infancy.
AB  - AIM: Despite its declining incidence, sudden infant death syndrome (SIDS) is
      still an important cause of death in infancy. This study investigated the
      environmental circumstances associated with SIDS, by analysing data from all
      sudden unexpected deaths in infancy (SUDI) in Sweden from 2005 to 2011. METHODS:
      All Swedish infants forensically autopsied up to the age of 365 days from 2005 to
      2011 were included. Medical records were obtained from the hospitals and
      supplementary data from the Swedish Medical Birth Register. RESULTS: Of the 261
      infants, 136 were defined as SIDS and 125 as explained SUDI. The documentation in
      the medical records was poor when it came to issues such as bed sharing, sleep
      position, smoking, breastfeeding and pacifier use. The main findings were a
      significantly higher prevalence of bed sharing in SIDS than in explained deaths
      (odds ratio 7.77, 95% confidence interval 2.36-25.57) and that prone sleeping was
      still overrepresented. Bronchopneumonia, other infections and congenital
      anomalies were the most common causes of explained SUDI. CONCLUSION: Bed sharing
      and prone sleeping were more common in SIDS than in explained SUDI. Sparse data
      in medical records were a problem, and the authors are now working with the
      National Board of Health and Welfare on a project to establish new routines.

PMID- 25865749
TI  - Electrophysiological evidence of statistical learning of long-distance
      dependencies in 8-month-old preterm and full-term infants.
AB  - Using electroencephalography, we examined 8-month-old infants' ability to
      discover a systematic dependency between the first and third syllables of
      successive words, concatenated into a monotonous speech stream, and to
      subsequently generalize this regularity to new items presented in isolation. Full
      term and preterm infants, while exposed to the stream, displayed a significant
      entrainment (phase-locking) to the syllabic and word frequencies, demonstrating
      that they were sensitive to the word unit. The acquisition of the systematic
      dependency defining words was confirmed by the significantly different neural
      responses to rule-words and part-words subsequently presented during the test
      phase. Finally, we observed a correlation between syllabic entrainment during
      learning and the difference in phase coherence between the test conditions (rule
      words vs part-words) suggesting that temporal processing of the syllable unit
      might be crucial in linguistic learning. No group difference was observed
      suggesting that non-adjacent statistical computations are already robust at 8
      months, even in preterm infants, and thus develop during the first year of life,
      earlier than expected from behavioral studies.

PMID- 25865750
TI  - Alternate-day dosing of itraconazole in healthy adult cats.
AB  - The current available formulations of itraconazole are not ideal for dosing in
      cats. The capsular preparation often does not allow for accurate dosing, the oral
      solution is difficult to administer and poorly tolerated, and the bioavailability
      of compounded formulations has been shown to be poor in other species. The aim of
      this study was to evaluate every other day dosing of 100 mg itraconazole capsule
      in healthy adult cats. Ten healthy adult cats received a 100 mg capsule of
      itraconazole orally every 48 h for 8 weeks. Peak and trough serum concentrations
      of itraconazole were measured weekly using high-performance liquid chromatography
      (HPLC). Physical examination, complete blood count (CBC), and chemistry profiles
      were performed weekly. The dosage regimen achieved average therapeutic trough
      concentrations (>0.5 MUg/mL) within 3 weeks. The protocol yielded no adverse
      effects in 8 of the 10 study cats, with affected cats recovering fully with
      discontinuation of the drug and supportive care. At 8 weeks, an average peak
      concentration of 1.79 +/- 0.952 MUg/mL (95% CI: 0.996-2.588) and an average
      trough concentration of 0.761 +/- 0.540 MUg/mL (95% CI: 0.314-1.216) were
      achieved. Overall, a 100 mg every other day oral dosage regimen for itraconazole
      in cats yielded serum concentrations with minimal fluctuation and with careful
      monitoring may be considered for treatment of cats with systemic fungal disease.

PMID- 25865751
TI  - Simultaneous ingestion of high-methoxy pectin from apple can enhance absorption
      of quercetin in human subjects.
AB  - Chronic ingestion of apple pectin has been shown to increase the absorption of
      quercetin in rats. The present study was designed to elucidate whether the
      simultaneous ingestion of quercetin with apple pectin could enhance the
      absorption of quercetin in humans, and the effects of dose dependency and degree
      of pectin methylation on quercetin absorption were also investigated. Healthy
      volunteers (n 19) received 200 ml of 0.5 mg/ml of quercetin drinks with or
      without 10 mg/ml of pectin each in a randomised cross-over design study with over
      1-week intervals; urine samples from all the subjects were collected within 24 h
      after ingestion of the test drinks, and urinary deconjugated quercetin and its
      metabolites were determined using HPLC. The sum of urinary quercetin and its
      metabolites excreted was increased by 2.5-fold by the simultaneous ingestion of
      pectin. The metabolism of methylated quercetin (isorhamnetin and tamarixetin) was
      not affected by pectin ingestion. In six volunteers, who received quercetin
      drinks containing 0, 3 and 10 mg/ml of pectin, the sum of urinary quercetin and
      its metabolites excreted also increased in a pectin dose-dependent manner.
      Furthermore, the simultaneous ingestion of quercetin with low-methoxy and high
      methoxy pectin, respectively, increased the sum of urinary excretion of quercetin
      and its metabolites by 1.69-fold and significantly by 2.13-fold compared with the
      ingestion of quercetin without pectin. These results elucidated that apple pectin
      immediately enhanced quercetin absorption in human subjects, and that its
      enhancing effect was dependent on the dose and degree of pectin methylation. The
      results also suggested that the viscosity of pectin may play a role in the
      enhancement of quercetin absorption.

PMID- 25865752
TI  - [Update of planning tables of cholesterol-lowering therapy orientated to achieve
      LDL therapeutic targets].
AB  - This is the third update of a planning-table for use in cholesterol-lowering
      therapy, so as to obtain LDLc objectives. This is an easy to use laptop tool to
      help choose the best statin or combination therapy (statin plus ezetimibe)
      depending on the current LDL concentration of the patient, and the LDLc objective
      to achieve. It is based on a colour code that indicates the drugs that are
      efficient enough to help patients to achieve their LDL goal. Along with the
      table, recommendations are given for the best strategy in order to implement the
      optimal therapy in a maximum of two clinical encounters. 

PMID- 25865753
TI  - Pursuing Innovation With the Tech Transfer Center.

PMID- 25865754
TI  - Kinetic Stability of MOF-5 in Humid Environments: Impact of Powder Densification,
      Humidity Level, and Exposure Time.
AB  - Metal-organic frameworks (MOFs) are an emerging class of microporous, crystalline
      materials with potential applications in the capture, storage, and separation of
      gases. Of the many known MOFs, MOF-5 has attracted considerable attention because
      of its ability to store gaseous fuels at low pressure with high densities.
      Nevertheless, MOF-5 and several other MOFs exhibit limited stability upon
      exposure to reactive species such as water. The present study quantifies the
      impact of humid air exposure on the properties of MOF-5 as a function of exposure
      time, humidity level, and morphology (i.e., powders vs pellets). Properties
      examined include hydrogen storage capacity, surface area, and crystallinity.
      Water adsorption/desorption isotherms are measured using a gravimetric technique;
      the first uptake exhibits a type V isotherm with a sudden increase in uptake at
      ~50% relative humidity. For humidity levels below this threshold only minor
      degradation is observed for exposure times up to several hours, suggesting that
      MOF-5 is more stable than generally assumed under moderately humid conditions. In
      contrast, irreversible degradation occurs in a matter of minutes for exposures
      above the 50% threshold. Fourier transform infrared spectroscopy indicates that
      molecular and/or dissociated water is inserted into the skeletal framework after
      long exposure times. Densification into pellets can slow the degradation of MOF-5
      significantly, and may present a pathway to enhance the stability of some MOFs. 

PMID- 25865755
TI  - Highly stretchable gold nanobelts with sinusoidal structures for recording
      electrocorticograms.
AB  - Rationally designed sinusoidal gold nanobelts are fabricated as stretchable
      electrodes, and they do not show obvious change of resistance under large
      deformation after 10,000 cyclic stretching/relaxing processes. As a proof of
      concept, they are successfully used to record intracranial electroencephalogram
      or electrocorticogram signals from rats.

PMID- 25865756
TI  - The stress-responsive gene ATF3 regulates the histone acetyltransferase Tip60.
AB  - Tat-interactive protein 60 (Tip60) is a MYST histone acetyltransferase that
      catalyses acetylation of the major DNA damage kinase Ataxia telangiectasia
      mutated (ATM), thereby triggering cellular signalling required for the
      maintenance of genomic stability on genotoxic insults. The Tip60 activity is
      modulated by post-translational modifications that alter its stability and its
      interactions with substrates. Here we report that activating transcription factor
      3 (ATF3), a common stress mediator and a p53 activator, is a regulator of Tip60.
      ATF3 directly binds Tip60 at a region adjacent to the catalytic domain to promote
      the protein acetyltransferase activity. Moreover, the ATF3-Tip60 interaction
      increases the Tip60 stability by promoting USP7-mediated deubiquitination of
      Tip60. Consequently, knockdown of ATF3 expression leads to decreased Tip60
      expression and suppression of ATM signalling as evidenced by accumulated DNA
      lesions and increased cell sensitivity to irradiation. Our findings thus reveal a
      previously unknown function of a common stress mediator in regulating Tip60
      function. 

PMID- 25865757
TI  - Would a new definition and classification of nocturia and nocturnal polyuria
      improve our management of patients? ICI-RS 2014.
AB  - The following is a report of the proceedings of the Nocturia Think Tank sessions
      of the annual International Consultation on Incontinence-Research Society, which
      took place September 22-24, 2014 in Bristol, UK. The report is organized into
      sections pertaining to the main topic of discussion focussing on the question as
      to whether a new definition and classification of nocturia and nocturnal polyuria
      would improve the outcome of management in our patients. First, discussions
      identified theoretical and practical shortcomings of current definitions.
      Secondly, the utility of several nocturnal polyuria definitions was tested in a
      real life population in relation to the symptom nocturia, in order to display
      weaknesses of these definitions. Thirdly, we explored in a clinical population
      the utility of bladder diary based parameters by asking the question: when
      nocturia improves, which of these parameters improve most? Based on the above
      explorations the Think Tank summarized elements of the current definitions that
      need reconsideration and suggests proposals for further research to reach more
      practical and more clinically meaningful definitions.

PMID- 25865758
TI  - A review of craniofacial disorders caused by spliceosomal defects.
AB  - The spliceosome is a large ribonucleoprotein complex that removes introns from
      pre-mRNA transcripts. Mutations in EFTUD2, encoding a component of the major
      spliceosome, have recently been identified as the cause of mandibulofacial
      dysostosis, Guion-Almeida type (MFDGA), characterized by mandibulofacial
      dysostosis, microcephaly, external ear malformations and intellectual disability.
      Mutations in several other genes involved in spliceosomal function or linked
      aspects of mRNA processing have also recently been identified in human disorders
      with specific craniofacial malformations: SF3B4 in Nager syndrome, an acrofacial
      dysostosis (AFD); SNRPB in cerebrocostomandibular syndrome, characterized by
      Robin sequence and rib defects; EIF4A3 in the AFD Richieri-Costa-Pereira
      syndrome, characterized by Robin sequence, median mandibular cleft and limb
      defects; and TXNL4A in Burn-McKeown syndrome, involving specific craniofacial
      dysmorphisms. Here, we review phenotypic and molecular aspects of these
      syndromes. Given the apparent sensitivity of craniofacial development to defects
      in mRNA processing, it is possible that mutations in other proteins involved in
      spliceosomal function will emerge in the future as causative for related human
      disorders. 

PMID- 25865759
TI  - A novel DO null allele with a c.268C>T (p.Gln90Stop) mutation in Japanese.
AB  - The Dombrock blood group system consists of two antithetical antigens, Do(a)
      (DO1) and Do(b) (DO2), and seven high-prevalence antigens, Gy(a) (DO3), Hy (DO4),
      Jo(a) (DO5), DOYA (DO6), DOMR (DO7), DOLG (DO8) and DOLC (DO9). Do(a) /Do(b)
      polymorphism is associated with c.793A>G (p.Asn265Asp) in exon 2 of the DO (ART4)
      gene, and the corresponding alleles are named DO*01 and DO*02. The rare Donull or
      Gy(a-) phenotype lacks all Dombrock antigens, and the DO null alleles vary with
      both DO*01 and DO*02 backgrounds. We report a novel DO null allele, which has a
      c.268C>T (p.Gln90Stop) nonsense mutation with a DO*02 background identified from
      four unrelated Gy(a-) Japanese individuals.

PMID- 25865760
TI  - Extracorporeal Membrane Oxygenation Support in Postcardiotomy Elderly Patients:
      The Mayo Clinic Experience.
AB  - BACKGROUND: We conducted a retrospective study to assess whether providing
      extracorporeal membrane oxygenation (ECMO) support to elderly patients (aged 70
      years or more) who failed separation from cardiopulmonary bypass after cardiac
      surgery was a viable option. METHODS: From 2003 to 2013, 45 patients aged 70
      years or more underwent 47 runs of ECMO postoperatively. RESULTS: There were 31
      men (68.9%). The mean age was 76.8 years. Five patients were in cardiogenic shock
      preoperatively. Forty-four patients required venoarterial ECMO support for
      cardiogenic shock. Mean duration of support was 103.8 +/- 74.3 hours. Twenty-one
      patients (46.6%) died while on ECMO support. Twenty-four patients (53.3%) were
      weaned off ECMO initially, and 11 patients were discharged from hospital.
      Inhospital mortality was 75.6%. Postoperative complications included acute kidney
      injury in 30 patients (44.4%), pneumonia in 12 (26.7%), and sepsis in 11 (24.4%).
      There were 30 deaths (88.2%) attributable to cardiac causes. Preoperative atrial
      fibrillation, chronic kidney injury, lactic acidosis on ECMO support, and
      persistent coagulopathy were associated with higher mortality. CONCLUSIONS:
      Postcardiotomy ECMO support in elderly patients is associated with high
      postoperative morbidity and mortality. Nevertheless, it often provides the last
      line of therapy for these critically ill patients and may provide positive
      outcomes in selected subgroups.

PMID- 25865761
TI  - Temporal Differences in Causes of Mortality After Left Ventricular Assist Device
      Implantation.
AB  - BACKGROUND: The risk of device-related adverse events leading to death is
      abundant and ever-present after left ventricular assist device (VAD)
      implantation. Very few data specifically examine the causes of death related to
      length of time after VAD implantation. METHODS: Between October 2004 and February
      2013, 493 patients (395 male, 80%) underwent primary continuous-flow VAD
      implantation at our institutions. The median age at implantation was 60 years
      (range, 18-79 years), and 301 patients (62%) underwent bridge to transplantation.
      RESULTS: Follow-up was available for all patients (median, 13 months) for a total
      of 717 patient-years of support. There were 132 deaths during follow-up (median,
      8 months; early, 5.5 years) after VAD implantation. The patients were grouped
      according to temporal occurrence of deaths: (1) early (30-day or index
      hospitalization) in 34 of 132 patients (26%), (2) between hospital dismissal and
      6 months in 29 of 132 patients (22%), (3) 6 months to 1 year in 14 of 132
      patients (11%), and (4) after 1 year in 55 of 132 patients (42%). The causes of
      death (%) at each time period are presented; the most common early cause was
      right ventricular failure/multisystem organ failure in 18 of 34 patients (61%);
      from dismissal to 6 months, and 6 months to 1 year, cerebral hemorrhage in 6 of
      29 patients (21%) and 4 of 14 patients (29%), respectively; after 1 year,
      cerebral hemorrhage in 12 of 55 patients (22%) and right ventricular
      failure/multisystem organ failure in 11 of 55 patients (20%). CONCLUSIONS: The
      causes of death vary according to time after VAD implantation. Understanding the
      temporal relationship of causes of mortality after VAD implantation is critical
      to the identification of varying specific risks in an effort to avoid morbidity,
      which may ultimately detract from a durable VAD outcome.

PMID- 25865762
TI  - A Regulated Trial of Bicuspid Aortic Valve Repair Supported by Geometric Ring
      Annuloplasty.
AB  - BACKGROUND: Annular stabilization is important during bicuspid aortic valve (BAV)
      repair to obtain the best long-term results. This report describes the early
      outcomes of a novel bicuspid annuloplasty ring for this purpose. METHODS: Under
      regulatory supervision (NCT02071849), a geometric bicuspid annuloplasty ring was
      used during valve repair in 16 patients. Three patients had Sievers type 0
      valves, 11 had Sievers type 1, and 2 had Sievers type 2. Thirteen patients had
      left-/right-coronary cusp fusion, 1 had right-/noncoronary cusp fusion, and 2 had
      both. Moderate to severe aortic insufficiency (AI) was present in 13 of 16
      patients, and 3 had mild AI with aortic aneurysms. Ascending aortic aneurysms,
      root aneurysms, or both were replaced in 7 of 16 patients. The Dacron-covered
      titanium ring had circular base geometry and two outwardly flaring subcommissural
      posts positioned opposite on the circumference. The ring was implanted into the
      annulus beneath the valve, and then leaflet repair was performed. RESULTS:
      Immediate postrepair echocardiograms showed grade 0 residual AI in all patients,
      with good cusp mobility and effective height, and satisfactory gradients. There
      were no in-hospital or late mortalities. Two patients experienced leaflet tears
      from long annular suture tails, requiring late valve replacement. After
      implementation of a lateral suture fixation technique, no more failures occurred.
      At a mean follow-up time of 9 months, the remaining 14 patients were in New York
      Heart Association class I, with predominant grade 0 AI. CONCLUSIONS: As a
      technique for BAV repair, internal ring annuloplasty produces major annular
      remodeling and stabilization. Annular reduction and reshaping to a 50/50%
      symmetric circular geometry facilitates leaflet repair and enhances cusp
      coaptation. Geometric ring annuloplasty could have useful applications in BAV
      repair.

PMID- 25865763
TI  - Coronary Artery Bypass Grafting After Percutaneous Intervention Has Higher Early
      Mortality: A Meta-Analysis.
AB  - BACKGROUND: We compared early adverse events and midterm survival between primary
      coronary artery bypass grafting (pCABG) and CABG in patients with percutaneous
      intervention (secondary CABG, sCABG) because data on this topic are very limited.
      METHODS: A systematic review of published literature was done to obtain original
      studies fulfilling the search criteria. The end points studied were early
      mortality, stroke, renal failure, myocardial infarction, and the need for an
      intra-aortic balloon pump. A random-effect inverse variance weighted analysis was
      performed. The results are presented as risk ratios (RR) (95% confidence
      interval); p < 0.05 was considered statistically significant. RESULTS: Fourteen
      studies (84,983 pCABG patients and 14,775 sCABG patients) were included in the
      systematic review. Early mortality was lower with primary CABG (RR 1.54 [1.19-2];
      p = 0.007). The incidence of myocardial infarction was also less with pCABG than
      with sCABG. (RR 1.46 [1.04-2.06]; p = 0.06). Patients undergoing pCABG were 14%
      (0% to 55%; p = 0.04). Less likely to need an intra-aortic balloon pump. Although
      renal failure was lower with pCABG (RR 1.254 [1.047-1.502]; p = 0.014), the
      stroke rates were comparable in both cohorts (p = 0.95). Renal failure was
      favorable in the primary CABG cohort. Early stroke was comparable between the two
      cohorts (p = 0.95). The pooled hazard ratios demonstrated comparable survival at
      the end of 3 years (p = 0.36). CONCLUSIONS: Patients undergoing CABG after prior
      percutaneous therapy have a higher incidence of myocardial infarction and
      mortality in the postoperative period. However, midterm survival is comparable in
      both cohorts.

PMID- 25865764
TI  - Impact of Surgical Stroke on the Early and Late Outcomes After Thoracic Aortic
      Operations.
AB  - BACKGROUND: Thoracic aortic operations still remain associated with substantial
      risks of death and neurologic injury. This study investigated the impact of
      surgical stroke on the early and late outcomes, focusing on the physical status
      and quality of life (QOL). METHODS: From 1986 to 2008, 500 patients (aged 63 +/-
      13 years) underwent open thoracic aortic repair for root and ascending (31%),
      arch (39%), extended arch (10%), and descending and thoracoabdominal (19%)
      aneurysms. Brain protection consisted of retrograde cerebral perfusion (52%),
      antegrade cerebral perfusion (29%), and simple deep hypothermic circulatory
      arrest (19%). Surgical stroke was defined as a neurologic deficit persisting more
      than 72 hours after the operation. QOL was assessed with the Short-Form 36 Health
      Survey Questionnaire 5.9 +/- 4.2 years after the operation. RESULTS: Stroke
      occurred in 10.3% of patients. Hospital mortality was 21% in the stroke group and
      2.7% in the nonstroke group (p < 0.001). At hospital discharge, 76% of survivors
      in the stroke group had permanent neurologic deficits (PNDs), with sustained
      tracheostomy in 39%, tube feeding in 46%, and gastrostomy in 14%, and 89%
      required transfer to other facilities. PND was an independent risk factor for
      late death (hazard ratio, 2.29; 95% confidence interval, 1.04 to 4.62; p = 0.041)
      in a multivariate analysis. The physical component of the QOL score was worse in
      the PND group (51% vs 100%; p = 0.039), whereas the mental component was similar
      in both groups (14% vs 14%). CONCLUSIONS: Surgical stroke is associated with high
      hospital mortality and PNDs that decrease late survival and the physical
      component score of the QOL survey.

PMID- 25865765
TI  - Spinal Cord Ischemia-Reperfusion Injury Induces Erythropoietin Receptor
      Expression.
AB  - BACKGROUND: Paraplegia remains a devastating complication of aortic surgery,
      occurring in up to 20% of complex thoracoabdominal repairs. Erythropoietin (EPO)
      attenuates this injury in models of spinal cord ischemia. Upregulation of the
      beta-common receptor (betacR) subunit of the EPO receptor is associated with
      reduced damage in murine models of neural injury. This receptor activates anti
      apoptotic pathways including signaling transducer and activator of transcription
      3 (STAT3). We hypothesized that spinal cord ischemia-reperfusion injury
      upregulates the betacR subunit with a subsequent increase in activated STAT3.
      METHODS: Adult male C57/BL6 mice received an intraperitoneal injection of 0.5 mL
      of EPO (10 U/kg) or 0.9% saline after induction of anesthesia. Spinal cord
      ischemia was induced through sternotomy and 4-minute thoracic aortic cross-clamp.
      Sham mice underwent sternotomy without cross-clamp placement. Four groups were
      studied: ischemic and sham groups, each with and without EPO treatment. After 4
      hours of reperfusion, spinal cords were harvested and homogenized. The betacR
      subunit expression and STAT3 activation were evaluated by immunoblot. RESULTS:
      Ischemia reperfusion increased betacR subunit expression in spinal cords of
      ischemia + saline and ischemia + EPO mice compared with shams (3.4 +/- 1.39 vs
      1.31 +/- 0.3, p = 0.01 and 3.80 +/- 0.58 vs 1.56 +/- 0.32, p = 0.01).
      Additionally, both ischemic groups demonstrated increased STAT3 activation
      compared with shams (1.35 +/- 0.14 vs 1.09 +/- 0.07, p = 0.01 and 1.66 +/- 0.35
      vs 1.08 +/- 0.17, p = 0.02). CONCLUSIONS: Ischemia-reperfusion injury induces EPO
      receptor betacR subunit expression and early downstream anti-apoptotic signaling
      through STAT3 activation. Further investigation into the role of the betacR
      subunit is warranted to determine tissue protective functions of EPO. Elucidation
      of mechanisms involved in spinal cord protection is essential for reducing
      delayed paraplegia.

PMID- 25865766
TI  - A "Repair-All" Strategy for Degenerative Mitral Valve Disease Safely Minimizes
      Unnecessary Replacement.
AB  - BACKGROUND: We examined the feasibility and efficacy of a "repair-all" strategy
      applied in all patients with degenerative mitral regurgitation, regardless of
      valve complexity, risk profile, and surgical approach. METHODS: Between 2002 and
      2011, 4,241 patients underwent mitral operations at our institution. Analysis was
      limited to 525 consecutive patients with mitral regurgitation due to leaflet
      prolapse (posterior, 75%; anterior, 5%; bileaflet, 20%) who underwent isolated
      mitral operations. A right minithoracotomy was used in 46% of procedures.
      Propensity scores identified 153 well-matched patient pairs for evaluation of the
      effect of surgical approach on valve reparability. RESULTS: Mitral repair was
      successful in 99% (520 of 525) of patients. The location of the leaflet prolapse
      did not significantly influence the repair rate or the need for intraoperative
      revision of the initial repair. The repair rate and the need for intraoperative
      repair revision also did not significantly differ by surgical approach.
      Intraoperative revision did not confer a greater risk of perioperative morbidity
      or longer length of stay. At 8 years, freedom from severe mitral regurgitation
      was 97% +/- 2%. Development of residual mitral regurgitation did not differ by
      location of the leaflet prolapse, need for repair revision, or surgical approach.
      After discharge, the survival trend did not differ between patients who did and
      did not require intraoperative repair revision. CONCLUSIONS: In experienced
      centers, a "repair-all" strategy for degenerative mitral regurgitation can be
      used with nearly 100% repair rates and excellent outcomes, regardless of valve
      complexity. When necessary, intraoperative revision of the initial repair may be
      performed in most patients without a significant incremental risk, thereby
      further enhancing repair rates.

PMID- 25865767
TI  - Feasibility and Early Safety of Single-Stage Hybrid Coronary Intervention and
      Valvular Cardiac Surgery.
AB  - BACKGROUND: Hybrid percutaneous coronary intervention offers an alternative
      method of revascularization for high-risk surgical populations. We report the
      outcomes of a single-stage hybrid strategy in valvular cardiac surgery and
      explore its effects on operative risk and bleeding. METHODS: In a hybrid
      operating room, 26 patients underwent hybrid surgery consisting of femoral
      arterial access, then coronary stenting followed by valve surgery, with
      appropriate heparin dosing. Clopidogrel (300 mg) was given on anesthesia
      induction in nonreoperative cases, or at the time of cross clamping (after
      stenting) for reoperative cases. RESULTS: Mean follow-up was 680 +/- 277 days.
      The planned coronary stenting and surgery was successful in all patients. Major
      cardiovascular and cerebrovascular adverse events occurred in 1 patient, with no
      inhospital deaths observed. No vascular complication or stent thrombosis was
      observed with the described antiplatelet regimen. Outcomes were comparable to
      those of standard bypass valve replacement surgery. CONCLUSIONS: This study
      demonstrates the feasibility and early safety of a single-stage hybrid strategy
      with coronary stenting followed by valvular surgery in patients at increased
      surgical risk. Hybrid procedures may lower operative risk by eliminating or
      reducing the need for bypass grafting.

PMID- 25865769
TI  - Animal experimentation--questioned again!

PMID- 25865768
TI  - Quantitative hopanoid analysis enables robust pattern detection and comparison
      between laboratories.
AB  - Hopanoids are steroid-like lipids from the isoprenoid family that are produced
      primarily by bacteria. Hopanes, molecular fossils of hopanoids, offer the
      potential to provide insight into environmental transitions on the early Earth,
      if their sources and biological functions can be constrained. Semiquantitative
      methods for mass spectrometric analysis of hopanoids from cultures and
      environmental samples have been developed in the last two decades. However, the
      structural diversity of hopanoids, and possible variability in their ionization
      efficiencies on different instruments, have thus far precluded robust
      quantification and hindered comparison of results between laboratories. These
      ionization inconsistencies give rise to the need to calibrate individual
      instruments with purified hopanoids to reliably quantify hopanoids. Here, we
      present new approaches to obtain both purified and synthetic quantification
      standards. We optimized 2-methylhopanoid production in Rhodopseudomonas palustris
      TIE-1 and purified 2Me-diplopterol, 2Me-bacteriohopanetetrol (2Me-BHT), and their
      unmethylated species (diplopterol and BHT). We found that 2-methylation decreases
      the signal intensity of diplopterol between 2 and 34% depending on the instrument
      used to detect it, but decreases the BHT signal less than 5%. In addition, 2Me
      diplopterol produces 10* higher ion counts than equivalent quantities of 2Me-BHT.
      Similar deviations were also observed using a flame ionization detector for
      signal quantification in GC. In LC-MS, however, 2Me-BHT produces 11* higher ion
      counts than 2Me-diplopterol but only 1.2* higher ion counts than the sterol
      standard pregnane acetate. To further improve quantification, we synthesized
      tetradeuterated (D4) diplopterol, a precursor for a variety of hopanoids. LC-MS
      analysis on a mixture of (D4)-diplopterol and phospholipids showed that under the
      influence of co-eluted phospholipids, the D4-diplopterol internal standard
      quantifies diplopterol more accurately than external diplopterol standards. These
      new quantitative approaches permit meaningful comparisons between studies,
      allowing more accurate hopanoid pattern detection in both laboratory and
      environmental samples.

PMID- 25865771
TI  - The Occurrence of Depersonalization Symptoms After Accelerated HF-rTMS of the
      Left DLPFC in a Patient With Treatment-resistant Depression: A Case Report.

PMID- 25865772
TI  - Projecting Navigated TMS Sites on the Gyral Anatomy Decreases Inter-subject
      Variability of Cortical Motor Maps.
AB  - BACKGROUND: Magnetic resonance images are being increasingly deployed in
      conjunction with navigated transcranial magnetic stimulation (nTMS) to account
      for inter-individual differences in brain anatomy as well as to reduce the
      variability of mapping findings. OBJECTIVE: However, despite the fact that the
      individual gyral anatomy has a significant impact on the TMS-induced electrical
      field distributions, these approaches still project the TMS coil positions as a
      plane grid of target points on the brain surface and fail to account for
      differences in cortex morphology. METHODS: In this study, we have introduced a
      technique for projecting nTMS sites onto the gyral anatomy to decrease the
      variability of cortical motor maps between subjects in normalized space. This
      involved interpolating the discrete map points in the normalized volume space and
      performing additional surface coregistration. RESULTS: By applying this
      technique, we increased the spatial overlap between the cortical maps of the
      extensor digitorum communis muscle between subjects from 80% to 100%. We also
      managed to significantly reduce the mean Euclidean distance between the average
      center of gravity and the average hotspots to the respective individual spots
      from 8 mm to 6.5 mm. CONCLUSION: Our approach facilitates the study of the
      functional topography of distinct behavioral properties with high spatial
      resolution, thereby constituting a valuable tool for precise group analysis of
      cortical TMS maps.

PMID- 25865773
TI  - Do cultures influence placebo response?

PMID- 25865774
TI  - Tissue invasion and metastasis: Molecular, biological and clinical perspectives.
AB  - Cancer is a key health issue across the world, causing substantial patient
      morbidity and mortality. Patient prognosis is tightly linked with metastatic
      dissemination of the disease to distant sites, with metastatic diseases
      accounting for a vast percentage of cancer patient mortality. While advances in
      this area have been made, the process of cancer metastasis and the factors
      governing cancer spread and establishment at secondary locations is still poorly
      understood. The current article summarizes recent progress in this area of
      research, both in the understanding of the underlying biological processes and in
      the therapeutic strategies for the management of metastasis. This review lists
      the disruption of E-cadherin and tight junctions, key signaling pathways,
      including urokinase type plasminogen activator (uPA), phosphatidylinositol 3
      kinase/v-akt murine thymoma viral oncogene (PI3K/AKT), focal adhesion kinase
      (FAK), beta-catenin/zinc finger E-box binding homeobox 1 (ZEB-1) and transforming
      growth factor beta (TGF-beta), together with inactivation of activator protein-1
      (AP-1) and suppression of matrix metalloproteinase-9 (MMP-9) activity as key
      targets and the use of phytochemicals, or natural products, such as those from
      Agaricus blazei, Albatrellus confluens, Cordyceps militaris, Ganoderma lucidum,
      Poria cocos and Silybum marianum, together with diet derived fatty acids gamma
      linolenic acid (GLA) and eicosapentanoic acid (EPA) and inhibitory compounds as
      useful approaches to target tissue invasion and metastasis as well as other
      hallmark areas of cancer. Together, these strategies could represent new,
      inexpensive, low toxicity strategies to aid in the management of cancer
      metastasis as well as having holistic effects against other cancer hallmarks. 

PMID- 25865776
TI  - Murine MicroRNA-214 regulates intracellular adhesion molecule (ICAM1) gene
      expression in genital Chlamydia muridarum infection.
AB  - The hallmark of chlamydial infection is the development of upper genital
      pathology in the form of hydrosalpinx and oviduct and/or tubal dilatation.
      Although molecular events leading to genital tissue presentation and cellular
      architectural remodelling are unclear, early-stage host immune responses are
      believed to contribute to these long-term sequelae. Recently, we reported the
      contribution of selected infection-associated microRNAs (miRs) in the generation
      of host immunity at early-stage infection (day 6 after intravaginal Chlamydia
      muridarum challenge in C57BL/6 mice). In this report, we describe the
      contribution of an infection-associated microRNA, i.e. miR-214, to host immunity.
      Chlamydia muridarum infection in the C57BL/6 mouse genital tract significantly
      down-regulated miR-214 while up-regulating intracellular adhesion molecule 1
      (ICAM1) gene expression. These in vivo observations were confirmed by
      establishing direct regulation of ICAM-1 by miR-214 in ex vivo genital cell
      cultures in the presence of miR-214 mimic and inhibitor. Because, ICAM-1
      contributes to recruitment of neutrophils following infection, we also
      demonstrated that alteration of ICAM1 by miR-214 in interleukin-17A-deficient (IL
      17A(-/-) ) mice correlated with reduction of neutrophils infiltrating genital
      tissue at day 6 after challenge. Additionally, these early-stage events resulted
      in significantly decreased genital pathology in IL-17A(-/-) mice compared with
      C57BL/6 mice. This report provides evidence for early-stage regulation of ICAM1
      by microRNAs, resulting in reduction of genital pathology associated with
      chlamydial infection. 

PMID- 25865777
TI  - Age-specific measles mortality during the late 19th-early 20th centuries.
AB  - Measles mortality fell prior to the introduction of vaccines or antibiotics. By
      examining historical mortality reports we sought to determine how much measles
      mortality was due to epidemiological factors such as isolation from major
      population centres or increased age at time of infection. Age-specific records
      were available from Aberdeen; Scotland; New Zealand and the states of Australia
      at the end of the 19th and beginning of the 20th centuries. Despite the relative
      isolation of Australia, measles mortality was concentrated in very young children
      similar to Aberdeen. In the more isolated states of Tasmania, Western Australia
      and Queensland adults made up 14-15% of measles deaths as opposed to 8-9% in
      Victoria, South Australia and New South Wales. Mortality in Iceland and Faroe
      Islands during the 1846 measles epidemic was used as an example of islands
      isolated from respiratory pathogens. The transition from crisis mortality across
      all ages to deaths concentrated in young children occurred prior to the earliest
      age-specific mortality data collected. Factors in addition to adult age of
      infection and epidemiological isolation such as nutritional status and viral
      virulence may have contributed to measles mortality outcomes a century ago. 

PMID- 25865778
TI  - Association between ultrasonographic parameters of Cesarean scar defect and
      outcome of early termination of pregnancy.
AB  - OBJECTIVE: To determine whether Cesarean scar defect (CSD) parameters assessed by
      transvaginal sonography (TVS) might affect the outcome of early termination of
      pregnancy (TOP) with mifepristone-misoprostol. METHODS: This was a retrospective
      review of 183 women with previous Cesarean delivery who received oral
      mifepristone and misoprostol for TOP. A successful TOP was defined by the absence
      of an intrauterine gestational sac, with no need for surgical intervention. CSD
      was diagnosed by TVS in the presence of a hypoechogenic indentation within the
      myometrium of the lower uterine segment at the site of a previous Cesarean
      incision. Women were analyzed in three subgroups according to size of defect
      (ratio of residual myometrial thickness over the defect to adjacent myometrial
      thickness < 30%, 30%-70% and > 70%). RESULTS: Of the 183 women, 43 (23.5%) had
      failure of TOP. Fifty-nine (32.2%) had CSD detectable at TVS, and these women had
      a higher failure rate of TOP than did those without CSD (38.9% vs 16.1%; P =
      0.001). CSD was associated significantly with failure of TOP (odds ratio, 3.32
      (95% CI, 1.64-6.75)). The TOP failure rates in relation to defect size in the
      myometrial thickness ratio < 30%, 30%-70% and > 70% subgroups were 57.1%, 25.0%
      and 18.2%, respectively. There was a linear trend in failure rate across these
      ratios (Cochran-Armitage trend test; P = 0.015). CONCLUSIONS: Women with CSD are
      at increased risk of failed TOP. Women with a defect in which the residual
      myometrial thickness was < 30% of the adjacent myometrial thickness tended to
      have a greater chance of failed TOP. CSD detected at TVS is of clinical relevance
      in counseling women with a history of Cesarean delivery who are considering TOP.
      Copyright (c) 2015 ISUOG. Published by John Wiley & Sons Ltd.

PMID- 25865779
TI  - Long-Term Outcome and Quality of Life in Aortic Type A Dissection Survivors.
AB  - BACKGROUND: Aortic dissection is a severe and sophisticated disease that is often
      linked with a number of possible complications. Our study concerns with long-term
      outcome and quality of life (QoL) in acute aortic dissection type A (AADA)
      survivors. METHODS: From January 1999 until December 2006, 120 consecutive
      patients with AADA received an emergency operation. Of the total number of
      patients, 84 were males (70.0%) and 36 females (30.0%), mean aged 59.8 +/- 12
      years with a mean follow-up (FU) of 99.2 +/- 6 months. RESULTS: Overall mortality
      was 39.1% during the observational period with a maximum of 156 months. SF-36
      observation showed a significant decay in both Physical Component Summary (PCS)
      and Mental Component Summary (MCS) in FUII (PCS = 38.4) versus FUI (PCS = 43.4, p
      = 0.013). CONCLUSION: With ongoing postoperative time, patients did not recover
      but instead have got worse in terms of QoL. The decrease in MCP and linked
      subscores is an underestimated factor in QoL and long-term outcome after AADA.
      This is especially true in younger patients, which are judged to compensate
      better than older patients.

PMID- 25865780
TI  - Effect of Advanced Age on Off-pump Coronary Artery Bypass Grafting.
AB  - OBJECTIVE:  To investigate the perioperative features of aged patients undergoing
      off-pump coronary artery bypass grafting (OPCABG) surgery, and identify the
      perioperative effect of advanced age on OPCABG. METHOD:  A total of 61 aged
      patients and 585 younger patients from August 2013 to June 2014 were enrolled in
      this study. The perioperative features were summarized, and the effects of
      advanced age on intraoperative variables, as well as the postoperative
      complications were identified using logistic regression analysis. RESULTS:  The
      anastomosis time of the target coronary artery and intraoperative dosage of
      vasoconstrictor drugs was significantly longer or higher in the aged patients.
      The incidence of the postoperative complications, such as atrial fibrillation,
      repetitive mechanical ventilation, gastrointestinal dysfunction, and renal
      insufficiency, were significantly higher in the aged patients. The intubation
      time and postoperative hospital stay were significantly longer in the aged
      patients. No significant difference was found between the two groups in
      cardiocerebrovascular accident and mortality. Multivariate logistic regression
      analysis revealed advanced age was the independent risk factor for coronary
      artery anastomosis time, vasoconstrictor dosage, repeated mechanical ventilation,
      atrial fibrillation, gastrointestinal dysfunction, as well as the intubation time
      and hospital stay. CONCLUSION:  OPCABG in aged patients was safe and effective
      for avoiding a significant increase for cardiocerebrovascular accident and
      mortality. Relatively, the tolerance of aged heart to stimulation was poor.
      Atrial fibrillation, repetitive mechanical ventilation, and gastrointestinal
      dysfunction were more likely to occur in aged patients. Advanced age made
      intubation time and hospital stay prolonged significantly.

PMID- 25865781
TI  - Growing up in an era of AIDS.

PMID- 25865782
TI  - HIV/AIDS, childhood and governance: sundering the bonds of human society.
AB  - There is a disharmonious resonance between the length of HIV infection in the
      individual human host and the length of a human generation. In brief, an infected
      person may have children, these may be orphaned and grow up to become infected,
      and afterwards they themselves may have children, who can be orphaned in turn.
      Hence, a basic unit of social structure in most human societies, the three
      generation bond between grandparents, parents and the current generation - and on
      into the future - is repeatedly torn apart in the absence of treatment, a vaccine
      or behaviour change. This situation should be read against the threat of growing
      viral resistance. Certain implications of these processes for the future are
      outlined and discussed. The paper notes the uncertain future confronting
      societies that already have a relatively high number of orphans, and considers
      some otherwise unexpected possibilities, as well as the dangers of assuming that
      large-scale orphaning necessarily leads to social unrest and disorder. 

PMID- 25865783
TI  - 'But where are our moral heroes?' An analysis of South African press reporting on
      children affected by HIV/AIDS.
AB  - Messages conveyed both explicitly and implicitly in the media play an important
      role in shaping the public's understanding of issues, as well as in shaping
      associated policy, programmes and popular responses to these issues. This paper
      applies discourse analysis to a series of articles about children affected by
      HIV/AIDS published in 2002/2003 in the English-language South African press. The
      analysis reveals layers of moral messaging present in the reporting, the
      cumulative effect of which is the communication of a series of moral judgements
      about who is and who is not performing appropriate roles in relation to children.
      Discourses of moral transgression, specifically on the part of African parents
      and 'families' for failing in their moral responsibilities towards their
      children, coalesce with discourses on anticipated moral decay among (previously
      innocent) children who lack their due care. A need for moral regeneration among
      South Africans (but implicitly black South Africans) contrasts with accolades for
      (usually white), middle-class individuals, who, it is implied, have gone beyond
      their moral duty to respond. The article argues that in each instance the
      particular moralism is questionable in light of both empirical evidence and the
      principles of human dignity that underlie the South African constitution.
      Children - and particularly 'AIDS orphans' - are often presented in the press as
      either quintessential, innocent victims of the epidemic or as potential
      delinquents. While journalists' intentions are likely to be positive when
      representing children in these ways, the paper argues that this approach is
      employed at a cost, both to the public's knowledge and attitudes around the
      impact of HIV/AIDS, and, more importantly, to the lives of children affected by
      the epidemic. 

PMID- 25865784
TI  - Childcare in poor urban settlements in Swaziland in an era of HIV/AIDS.
AB  - This paper explores the role of the family in caring for orphans and other
      children in poor urban communities having some of the highest levels of HIV/AIDS
      prevalence in the world. A range of family forms in Swaziland was found to be
      caring for orphans. Child-headed households and lone-elderly carers were not the
      most common; maternal kin played a more important role in orphan care than did
      paternal kin, indicating both stresses due to AIDS and the dynamic nature of the
      family. Women of all ages were bearing the brunt of the extra care
      responsibilities caused by the epidemic. There was limited involvement in
      children's well-being by agencies of any kind and orphan care remained largely
      situated within kin structures. The AIDS epidemic was impacting on families in a
      variety of ways, with a corresponding increase in poverty and vulnerability.
      Carers did not perceive orphans as a separate category of children requiring
      assistance over and above any other vulnerable child. Families require assistance
      at the household, community and national level. Meanwhile, community-based
      initiatives were poorly developed. Welfare sector policies should strengthen the
      family model of childcare by increasing support to the poorest families rather
      than treating orphans as a separate category of vulnerable children and thereby
      excluding other needy children. 

PMID- 25865785
TI  - Positioning children and institutions of childcare in contemporary Uganda.
AB  - Currently more than half the population of Uganda is under 18 years - a
      demographic dispensation caused by civil war, poverty, high fertility rates, and
      the AIDS epidemic. Drawing upon ethnographic research in south-eastern Uganda,
      the study analyses the difficulties of integrating increasing numbers of
      adolescent orphans and other vulnerable children into Ugandan society. Aid
      workers and researchers generally agree that the extended family should be the
      first choice for assuming care of orphans and other vulnerable children, while
      they regard institutional care as a last resort. This article questions this
      common view. The author argues that understanding the consequences of childcare
      demands consideration for childcare settings, the interpersonal relationships
      between care-giver(s) and care-recipient(s), and the cultural notions of
      childcare. By focusing on children's position in society, while examining issues
      such as patterns of parental relations, leviratic practices, and the importance
      of land ownership and education for children's long-term well-being, the author
      contributes to understanding the complexity and changing patterns of childcare
      relations. Such patterns, she argues, call into question whether or not family
      caretaking should persistently be given preference over support in institutional
      settings like boarding schools. 

PMID- 25865786
TI  - What do Tanzanian children worry about?
AB  - This paper explores the worries of children in a sample of 8- to 15-year-old
      children, drawn from three primary schools on the outskirts of Moshi, Tanzania.
      Data about children's worries were collected by two methods. First, lists of
      worries were generated by 270 children who gave a total of 3 409 statements. The
      worries they expressed were categorised and condensed into 55 questions on a
      questionnaire designed to measure the frequency of the most common worries. In
      part two, 978 children participated by filling in this questionnaire. The
      majority of the children's worries fell into four categories: education, health,
      care/abuse and safety issues. The children elaborated on worries within each of
      these groups, whether or not they themselves were affected by HIV/AIDS through
      orphan-hood. However, their statements demonstrate their serious concern with the
      epidemic in the community and society. Concern for others above self is mirrored
      in the children's worries, reflecting the collective orientation of the local
      culture. Finally, ways that this knowledge may be utilised to strengthen
      children's coping strategies are discussed. 

PMID- 25865787
TI  - Beyond liminality: orphanhood and marginalisation in Botswana.
AB  - For children, the death of a parent initiates a rite of passage, a three-stage
      process: separation from their status as 'son' or 'daughter', a period of
      liminality with rituals of mourning, burial and interment, and finally re
      aggregation into a re-formed social network with a new status as a 'child without
      parents'. Many orphans in Botswana are excluded from the funerals of their
      parents; they are structurally invisible. Sometimes, particularly in the case of
      young children, they are taken to another place, thus they are literally not
      seen. In the case of older children, some complete all three stages of the rite
      of passage and the transformation results in clear aggregation into a new status
      and role. Those children are often resilient and cope well with the trials of
      orphanhood. For others, liminality is prolonged and the orphans are not
      reincorporated into a new social network; they are marginalised and may seek
      'belonging', 'acceptance' and 'membership' in alternative relationships and in
      socially unacceptable ways. This paper uses Van Gennep's concept of rite of
      passage as a framework for examining the coping strategies of orphans in
      Botswana, where some children demonstrate resilience as they emerge from
      liminality while others seem stuck in perpetual marginalisation. 

PMID- 25865788
TI  - Loveness and her brothers: trajectories of life for children orphaned by HIV/AIDS
      in Zambia.
AB  - A central theme in the contemporary rhetoric of those charged with managing
      HIV/AIDS interventions is how to handle and alleviate the plight of orphans and
      other vulnerable children (OVCs). The many glossy documents describing the policy
      and action plans of funders and organisations involved in AIDS work often
      highlight these children. Unfortunately, this does not necessarily result in
      increased support for research about children affected by HIV/AIDS, or even the
      increased allocation of resources to improve their life-situation. Discourse
      surrounding OVCs appears, in effect, to be barely more than a politically correct
      strategy for attracting resources while conveying the impression that concern for
      OVCs is a humane and central aspect of HIV/AIDS prevention and mitigation. In
      many rural African villages, however, the plight of orphans continues unmitigated
      and unaffected by the larger structures of purported interventions. These bold
      charges are supported by the following narrative account of a group of siblings
      in Zambia for one decade, as derived from a longitudinal micro study. It follows
      the children from the onset of parental death, through successive transfers to
      the homes of various relatives, ending with a sad form of closure: return to the
      ruins of their natal home as a child-headed household trying to make ends meet.
      The plight of these children epitomises an experience common to many children
      orphaned by AIDS, who are suffering without mitigation from the surrounding
      structures that exist to help vulnerable children. 

PMID- 25865789
TI  - The children left to stand alone.
AB  - Drawing upon ethnographic fieldwork in Seke, a semi-rural area outside Harare,
      Zimbabwe, this paper explores the social mechanism behind the seeming
      invisibility of children left on their own and how this form of 'invisibility'
      challenges established notions of childhood, parenthood, kinship, and community.
      It argues that the prevailing explanations, such as HIV/AIDS-related stigma,
      poverty or anomie, are insufficient for understanding the isolation of the child
      headed household and situations when children, in what should be a protective
      relationship, are exploited or abused. Through a detailed case-study, the paper
      explores the trajectory leading to the isolation of one particular child-headed
      household. It questions the biological assumptions that guide kinship
      interpretations and discusses the marriage transactions (the lobola exchange)
      that secure identity and belonging to the father's kin unit. Finally, it suggests
      that orphaned children ultimately stand alone because they are left in a specific
      time, in a specific situation, when the relationships that should surround them
      still have to be made, recognised and named. 

PMID- 25865790
TI  - Primary hepatocyte imaging by multiphoton luminescent graphene quantum dots.
AB  - Water soluble GQDs were systematically characterized as a multiphoton fluorophore
      and a cell imaging probe. When mouse primary hepatocytes were incubated with
      GQDs, no significant cytotoxicity was observed up to the treatment concentration
      of 100 MUg ml(-1). Using these GQDs, mouse primary hepatocytes were successfully
      imaged by multiphoton fluorescence. 

PMID- 25865791
TI  - Clinical and Molecular Comparison of Pediatric and Adult Reverse Remodeling With
      Ventricular Assist Devices.
AB  - Ventricular assist device (VAD) support induces reverse remodeling of failing
      myocardium that leads to occasional functional recovery of the adult heart. While
      there have been numerous clinical reports in adult patients with end-stage
      cardiomyopathy, little is known about reverse remodeling in children, which has
      increasing clinical potential with the recent expansion of pediatric VADs in the
      setting of static organ supply for heart transplantation. Pediatric myocardium
      also promises theoretical advantages for recovery over adult myocardium due to
      its greater abundance of cardiac progenitor cells. To identify potential targets
      of future studies, we conducted a literature review with two aims: (i) to
      summarize clinical cases of pediatric patients who exhibited cardiac recovery
      following VAD support; and (ii) to analyze genetic changes in pediatric
      myocardium induced by VAD support compared with those observed in adult patients.
      Several clinical series of pediatric VAD cases report that small proportions of
      their cohorts were weaned off from device support, but a lack of information
      about the etiology and support duration of these patients limits the ability to
      determine whether they represent reverse remodeling of myocardial structure or
      just recovery from acute illness. A comparison of pediatric and adult gene
      expression changes with VAD support reveals approximately 40% of genes to be
      oppositely regulated, indicating that the pediatric genetic response is distinct.
      These observations highlight a necessity to better understand reverse remodeling
      specific to pediatric myocardium, which is crucial to improving clinical
      strategies for bridge-to-recovery in children. 

PMID- 25865775
TI  - Cancer prevention and therapy through the modulation of the tumor
      microenvironment.
AB  - Cancer arises in the context of an in vivo tumor microenvironment. This
      microenvironment is both a cause and consequence of tumorigenesis. Tumor and host
      cells co-evolve dynamically through indirect and direct cellular interactions,
      eliciting multiscale effects on many biological programs, including cellular
      proliferation, growth, and metabolism, as well as angiogenesis and hypoxia and
      innate and adaptive immunity. Here we highlight specific biological processes
      that could be exploited as targets for the prevention and therapy of cancer.
      Specifically, we describe how inhibition of targets such as cholesterol synthesis
      and metabolites, reactive oxygen species and hypoxia, macrophage activation and
      conversion, indoleamine 2,3-dioxygenase regulation of dendritic cells, vascular
      endothelial growth factor regulation of angiogenesis, fibrosis inhibition,
      endoglin, and Janus kinase signaling emerge as examples of important potential
      nexuses in the regulation of tumorigenesis and the tumor microenvironment that
      can be targeted. We have also identified therapeutic agents as approaches, in
      particular natural products such as berberine, resveratrol, onionin A,
      epigallocatechin gallate, genistein, curcumin, naringenin, desoxyrhapontigenin,
      piperine, and zerumbone, that may warrant further investigation to target the
      tumor microenvironment for the treatment and/or prevention of cancer. 

PMID- 25865792
TI  - Organ donation among Malaysian Muslims: the role of mosques.
AB  - BACKGROUND: Malaysia, a country of Muslim majority, is suffering from a severe
      organ shortage due to the lack of donors. Mosques are the main gateways into the
      Muslim community. Hence, it is imperative to explore their role in facilitating
      organ donation. MATERIAL AND METHODS: A self-administered survey was conducted
      between October and December 2013. We distributed 700 pilot-tested questionnaires
      to 82 mosques in Kuala Lumpur and its suburbs. The respondents were stratified
      into 2 groups: the mosque committees and the Muslim Jama'ah (individuals who come
      regularly to mosque for prayer). RESULTS: Data collected from a survey on 653
      Malaysian Muslims reveals that the main factors that hamper organ donation
      related activities at the mosques in Malaysia are the lack of experts and
      financial resources. The level of autonomy of the mosque is also another main
      issue. The respondents believe that talks and dialogues are the best methods for
      organ donation campaigns at the mosques. Conclusions We argue that if the mosques
      are to play a role in imparting knowledge on organ donation, there should be
      ample opportunity for the mosque committee to choose the content of religious
      talks held in their community. The mosques in Malaysia are not sufficiently
      facilitated to channel the information on organ donation to the Muslim community.
      Providing financial support and expert campaigners are expected to increase organ
      donation-related activities at the mosques and subsequently could increase
      awareness regarding organ donations among Malaysian Muslims.

PMID- 25865793
TI  - Glycogen catabolism, but not its biosynthesis, affects virulence of Fusarium
      oxysporum on the plant host.
AB  - The role of glycogen metabolism was investigated in the fungal pathogen Fusarium
      oxysporum. Targeted inactivation was performed of genes responsible for glycogen
      biosynthesis: gnn1 encoding glycogenin, gls1 encoding glycogen synthase, and gbe1
      encoding glycogen branching enzyme. Moreover genes involved in glycogen
      catabolism were deleted: gph1 encoding glycogen phosphorylase and gdb1 encoding
      glycogen de-branching enzyme. Glycogen reserves increased steadily during growth
      of the wild type strain in axenic cultures, to reach up to 1500MUg glucose
      equivalents mg(-1) protein after 14 days. Glycogen accumulation was abolished in
      mutants lacking biosynthesis genes, whereas it increased by 20-40% or 80%,
      respectively, in the single and double mutants affected in catabolic genes.
      Transcript levels of glycogen metabolism genes during tomato plant infection
      peaked at four days post inoculation, similar to the results observed during
      axenic culture. Significant differences were observed between gdb mutants and the
      wild type strain for vegetative hyphal fusion ability. The single mutants
      defective in glycogen metabolism showed similar levels of virulence in the
      invertebrate animal model Galleria mellonella. Interestingly, the deletion of
      gdb1 reduced virulence on the plant host up to 40% compared to the wild type in
      single and in double mutant backgrounds, whereas the other mutants showed the
      virulence at the wild-type level.

PMID- 25865794
TI  - The acid trehalase, ATM1, contributes to the in vivo growth and virulence of the
      entomopathogenic fungus, Metarhizium acridum.
AB  - For pathogens, the ability to acquire available nutrients in a host is a key to
      their survival and replication. Entomopathogenic fungi of the genus Metarhizium
      secrete trehalase, which enables them to use trehalose, the predominant sugar in
      insects. Here, the roles of the acid trehalase gene (ATM1) in the in vivo growth
      and virulence of Metarhizium acridum were investigated. Phenotypic analysis
      showed that disruption of ATM1 severely reduced fungal growth on exogenous
      trehalose as the sole carbon source. Bioassays showed that ATM1 disruption
      impaired the virulence of M. acridum against the host insect Locusta migratoria.
      The ATM1-disruption strain (DeltaATM1) grown more slowly than the wild-type
      strain (WT) and complemented transformant (CP) in locust blood, which was
      consistent with the activity of acid trehalase in the hemolymph of infected
      locusts. Correspondingly, the trehalose concentration in locusts infected by
      DeltaATM1 was significantly higher than in those infected by WT or CP. Thus, ATM1
      disruption led to a significant reduction in virulence by adversely affecting the
      fungal growth in insect hemolymph, which resulted from the inability of the
      mutant strain to use trehalose. 

PMID- 25865795
TI  - Selenium speciation using capillary electrophoresis coupled with modified
      electrothermal atomic absorption spectrometry after selective extraction with 5
      sulfosalicylic acid functionalized magnetic nanoparticles.
AB  - A new method for selenium speciation in fermented bean curd wastewater and juice
      was described. This method involved sample extraction with 5-sulfosalicylic acid
      (SSA)-functionalized silica-coated magnetic nanoparticles (SMNPs), capillary
      electrophoresis (CE) separation, and online detection with a modified
      electrothermal atomic absorption spectrometry (ETAAS) system. The modified
      interface for ETAAS allowed for the introduction of CE effluent directly through
      the end of the graphite tube. Elimination of the upper injection hole of the
      graphite tube reduced the loss of the anlayte and enhanced the detection
      sensitivity. The SSA-SMNPs were synthesized and used to extract trace amounts of
      selenite [Se(IV)], selenite [Se(VI)], selenomethionine (SeMet), and selenocystine
      (SeCys2) from dilute samples. The concentration enrichment factors for Se(VI),
      Se(IV), SeMet, and SeCys2 were 21, 29, 18, and 12, respectively, using the SSA
      SMNPs extraction. The limits of detection for Se(VI), Se(IV), SeMet, and SeCys2
      were 0.18, 0.17, 0.54, 0.49ngmL(-1), respectively. The RSD values (n=6) of method
      for intraday were observed between 0.7% and 2.9%. The RSD values of method for
      interday were less than 3.5%. The linear range of Se(VI) and Se(IV) were in the
      range of 0.5-200ngmL(-1), and the linear ranges of SeMet and SeCys2 were 2-500
      and 2-1000ngmL(-1), respectively. The detection limits of this method were
      improved by 10 times due to the enrichment by the SSA-SMNP extraction. The
      contents of Se(VI) and Se(IV) in fermented bean curd wastewater were measured as
      3.83 and 2.62ngmL(-1), respectively. The contents of Se(VI), Se(IV), SeMet, and
      SeCys2 in fermented bean curd juice were determined as 6.39, 4.08, 2.77, and
      4.00ngmL(-1), respectively. The recoveries were in the range of 99.14-104.5% and
      the RSDs (n=6) of recoveries between 0.82% and 3.5%. 

PMID- 25865796
TI  - Multiresidue pesticide analysis in nutraceuticals from green tea extracts by
      comprehensive two-dimensional gas chromatography with time-of-flight mass
      spectrometry.
AB  - A new analytical method was developed and validated for simultaneous analysis of
      423 pesticides, isomers, and pesticide metabolites in nutraceutical products
      obtained from green tea (Camellia sinensis) extract. Response surface methodology
      was employed to optimize a generic extraction method. The automated extraction
      procedure was achieved in a simple disposable pipet extraction. Comprehensive two
      dimensional gas chromatography with time-of-flight mass spectrometry was used for
      the separation and detection of all the analytes. The method was validated by
      taking into consideration the guidelines specified in European SANCO/12571/2013
      Guideline 2013 and Commission Decision 2002/657/EC. The extraction recoveries
      were in a range of 81.6-113.0%, with coefficient of variation <6.4%. The limits
      of decision for the analytes are in the range 0.04-4.15MUgkg(-1). The detection
      capabilities for the analytes are in the range 0.07-6.92MUgkg(-1). The 423
      compounds behave dynamic in the range 0.1-200MUgkg(-1) concentration, with
      correlation coefficient >0.99. This validated method has been successfully
      applied on screening of pesticide residues in one hundred and twenty-four
      different commercial nutraceutical products from green tea extract, and
      methamidophos, resmethrin, propoxur, tridemorph, ethiofencarb, flamprop
      isopropyl, furalaxyl, bifenthrin and fenpropathrin were detected in a few samples
      tested in this study. 

PMID- 25865797
TI  - [Physics of materials and female stress urinary continence: New concepts: I)
      Elasticity under bladder].
AB  - OBJECTIVE: Improving the understanding of the adaptation to stress of urinary
      continence. METHOD: A transversal analysis between physics of materials and the
      female anatomy. Laws of physics of the materials and of their viscoelastic
      behavior are applied to the anatomy of the anterior vaginal wall. RESULT: The
      anterior vaginal wall may be divided into two segments of different viscoelastic
      behavior, the vertical segment below the urethra and the horizontal segment below
      the bladder. If the urethra gets crushed on the first segment according to the
      hammock theory, the crushing of the bladder on the second segment is, on the
      other hand, damped by its important elasticity. The importance of this elasticity
      evokes an unknown function: damping under the bladder that moderates and delays
      the increase of intravesical pressure. This damping function below the bladder is
      increased in the cystocele, which is therefore a continence factor; on the other
      hand, it is impaired in obesity, which is therefore a factor of SUI. CONCLUSION:
      It is necessary to include in the theory of stress continence, the notion of a
      damping function below the bladder.

PMID- 25865798
TI  - An experimental test of density-dependent selection on temperament traits of
      activity, boldness and sociability.
AB  - Temperament traits are seen in many animal species, and recent evolutionary
      models predict that they could be maintained by heterogeneous selection. We
      tested this prediction by examining density-dependent selection in juvenile
      common lizards Zootoca vivipara scored for activity, boldness and sociability at
      birth and at the age of 1 year. We measured three key life-history traits
      (juvenile survival, body growth rate and reproduction) and quantified selection
      in experimental populations at five density levels ranging from low to high
      values. We observed consistent individual differences for all behaviours on the
      short term, but only for activity and one boldness measure across the first year
      of life. At low density, growth selection favoured more sociable lizards, whereas
      viability selection favoured less active individuals. A significant negative
      correlational selection on activity and boldness existed for body growth rate
      irrespective of density. Thus, behavioural traits were characterized by limited
      ontogenic consistency, and natural selection was heterogeneous between density
      treatments and fitness traits. This confirms that density-dependent selection
      plays an important role in the maintenance of individual differences in
      exploration-activity and sociability.

PMID- 25865799
TI  - Current activities of the Yersinia effector protein YopM.
AB  - Yersinia outer protein M (YopM) belongs to the group of Yop effector proteins,
      which are highly conserved among pathogenic Yersinia species. During infection,
      the effectors are delivered into the host cell cytoplasm via the type 3 secretion
      system to subvert the host immune response and support the survival of Yersinia.
      In contrast to the other Yop effectors, YopM does not possess a known enzymatic
      activity and its molecular mechanism(s) of action remain(s) poorly understood.
      However, YopM was shown to promote colonization and dissemination of Yersinia,
      thus being crucial for the pathogen's virulence in vivo. Moreover, YopM interacts
      with several host cell proteins and might utilize them to execute its anti
      inflammatory activities. The results obtained so far indicate that YopM is a
      multifunctional protein that counteracts the host immune defense by multiple
      activities, which are at least partially independent of each other. Finally, its
      functions seem to be also influenced by differences between the specific YopM
      isoforms expressed by Yersinia subspecies. In this review, we focus on the global
      as well as more specific contribution of YopM to virulence of Yersinia during
      infection and point out the various extra- and intracellular molecular functions
      of YopM. In addition, the novel cell-penetrating ability of recombinant YopM and
      its potential applications as a self-delivering immunomodulatory therapeutic will
      be discussed. 

PMID- 25865800
TI  - Fibroblasts support migration of monocyte-derived dendritic cells by secretion of
      PGE2 and MMP-1.
AB  - The outcome of a cutaneous immune response is critically dependent upon the
      ability of dendritic cells (DC) to migrate from skin to the draining lymph nodes 
      a process that is influenced by the cutaneous tissue microenvironment. Here, the
      role of fibroblasts - a major component of the dermal microenvironment - on the
      migratory capacity of monocyte-derived DC (MoDC) was investigated in a 3D
      collagen I matrix. Indeed, dermal fibroblasts supported the migration of pre
      activated MoDC through a 3D collagen I matrix. Activation of human MoDC resulted
      in the release of TNFalpha and IL-1beta that in turn stimulated MMP-1 (human
      collagenase) and PGE2 secretion by human dermal fibroblasts. Transmigration
      assays confirmed the importance of fibroblast-derived MMP-1 and PGE2 for the
      migration of MoDC through a 3D collagen I matrix. Finally, in mice initiation of
      inflammation by induction of an irritant contact dermatitis or a psoriasis-like
      skin inflammation, the expression of the PGE2 generating cox-2 and the mouse
      collagen I degrading enzyme matrix metalloproteinases (MMP)-13 was strongly up
      regulated. Our study indicates that MoDC are able to instruct dermal fibroblasts
      resulting in enhanced migratory capability of MoDC, thus highlighting the role of
      a crosstalk of DC with their stromal microenvironment for the control of
      cutaneous immune responses. 

PMID- 25865802
TI  - Radiotherapy utilization in BRAF mutation-tested metastatic melanoma in the
      targeted therapy era.
AB  - AIM: Tumor BRAF mutation testing is routine for all patients with metastatic
      melanoma (MM) owing to the availability of agents targeting this intracellular
      pathway. To test whether there is a difference in radiotherapy (RT) utilization
      according to BRAF mutation status, we performed a retrospective review of RT
      utilization in a contemporary cohort undergoing BRAF mutation testing. METHODS:
      Clinical records of MM patients undergoing BRAF mutation testing between April
      2010 and August 2012 were reviewed. Overall survival (OS) was calculated using
      Kaplan-Meier methods. Differences between BRAF status were calculated using chi
      square tests for categorical variables, median tests for continuous variables and
      Cox proportional hazards models to compare OS. RESULTS: Up to 158 patients were
      identified but 17 were excluded due to inadequate clinical data. Of the remaining
      141 patients, 69 (49%) tested BRAF mutant (BRAF-m), median age 47 years (range 21
      79) with median follow-up of 16.8 months (IQR11.3-25.2). Seventy-two (51%) tested
      BRAF wild type (BRAF-w), median age 62 years (range 25-84) with median follow-up
      of 27.1 months (IQR12.5-57.4). Overall, RT utilization was similar: 68% in BRAF-m
      and 69% in BRAF-w. Mean number of treatment courses was 1.70 for BRAF-m and 2.36
      for BRAF-w (Pearson chi-square 3.92, P = 0.05). Up to 51% of BRAF-m and 56% of
      BRAF-w required ?2 RT courses. Forty-six percent BRAF-m compared with 29% BRAF-w
      received brain RT (P = 0.04). Median OS was 17.7 months (IQR7.6-35.5) in BRAF-m
      and 19 months (IQR7.8-35.1) in BRAF-w (P = 0.99). CONCLUSION: High RT utilization
      rates were observed irrespective of BRAF mutation status. Significantly more BRAF
      w patients received RT but more BRAF-m patients received brain RT.

PMID- 25865801
TI  - Logging cuts the functional importance of invertebrates in tropical rainforest.
AB  - Invertebrates are dominant species in primary tropical rainforests, where their
      abundance and diversity contributes to the functioning and resilience of these
      globally important ecosystems. However, more than one-third of tropical forests
      have been logged, with dramatic impacts on rainforest biodiversity that may
      disrupt key ecosystem processes. We find that the contribution of invertebrates
      to three ecosystem processes operating at three trophic levels (litter
      decomposition, seed predation and removal, and invertebrate predation) is reduced
      by up to one-half following logging. These changes are associated with decreased
      abundance of key functional groups of termites, ants, beetles and earthworms, and
      an increase in the abundance of small mammals, amphibians and insectivorous birds
      in logged relative to primary forest. Our results suggest that ecosystem
      processes themselves have considerable resilience to logging, but the consistent
      decline of invertebrate functional importance is indicative of a human-induced
      shift in how these ecological processes operate in tropical rainforests. 

PMID- 25865803
TI  - P-selectin enhances growth and metastasis of mouse mammary tumors by promoting
      regulatory T cell infiltration into the tumors.
AB  - AIMS: P-selectin is an adhesion receptor that is mainly present on endothelial
      cells and platelets. We investigated the role of P-selectin in the regulation of
      different T cell subsets in the tumor microenvironment, and how that influences
      the growth and metastasis of mouse mammary cancer cell line 4T1 in Balb/c mice.
      MAIN METHODS: The 4T1 cells (1*10(4) or 1*10(5)) were inoculated subcutaneously
      in the pre-shaved back skin of the P-selectin knockout (P-sel-/-) and wild-type
      (WT) mice. Mice were monitored twice weekly for the tumor growth measurements and
      survival studies. The tumors and the lungs were isolated for cytokine and T cell
      subset analyses at the end of the study. KEY FINDINGS: Mice lacking P-selectin
      had reduced tumor burden, higher survival and reduced metastasis compared to WT
      mice. Loss of P-selectin inhibited the infiltration of regulatory T cells and
      reduced pro-inflammatory cytokines, such as IL-4, IL-10, and TGFbeta in the
      tumors. Furthermore, the CD8+ T cells and effector CD4+ T cells were functional
      and exhibited enhanced infiltration into the tumors of P-selectin knockout mice
      compared to WT mice. SIGNIFICANCE: These results demonstrated that P-selectin is
      an important adhesion molecule vital for infiltration of regulatory T cells into
      the tumors. Thus, inhibiting P-selectin can have important therapeutic
      implications against breast cancer growth and metastasis.

PMID- 25865804
TI  - Linking a compound-heterozygous Parkin mutant (Q311R and A371T) to Parkinson's
      disease by using proteomic and molecular approaches.
AB  - Parkin is an E3-protein ubiquitin ligase, which plays an important role as a
      scavenger in cell metabolism. Since the discovery of the link between Parkin and
      Parkinson's disease, Parkin was placed in the center of Parkinson's disease
      research. Previously, we isolated a mutant form of the Parkin protein (Q311R and
      A371T) from a Parkinson's disease patient. In this study, we aimed at
      characterizing this mutant Parkin protein by using biochemical and proteomic
      approaches. We used neuroblastoma cells (SH-SY5Y) as our model and created two
      inducible cell lines that expressed the wild type and the mutant Parkin proteins.
      We first investigated the effect of expressing both the wild type and the mutant
      Parkin proteins on the overall proteome by using 2D-DIGE approach. The
      experiments yielded the identification of 22 differentially regulated proteins,
      of which 13 were regulated in the mutant Parkin expressing cells. Classification
      of the identified proteins based on biological process and molecular function
      revealed that the majority of the regulated proteins belonged to protein folding
      and energy metabolism. Ingenuity Pathway Analysis predicted the presence of a
      link between the regulated proteins of the mutant Parkin expressing cells and
      Parkinson's disease. We also performed biochemical characterization studies on
      the wild type and the mutant Parkin proteins to make sense out of the differences
      observed at the proteome level. Both proteins displayed biological activity, had
      similar stabilities and localized similarly to the cytoplasm and the nucleus in
      SH-SY5Y cells. The mutant protein, however, was cut by a protease and subjected
      to a post-translational modification. The observed differences at the proteome
      level might be due to the differences in processing of the mutant Parkin protein.
      Overall, we were able to create a possible link between a pair of Parkin
      mutations to its pertinent disease by using 2D-DIGE in combination with
      biochemical and molecular approaches. 

PMID- 25865805
TI  - Biodiversity in cities needs space: a meta-analysis of factors determining intra
      urban biodiversity variation.
AB  - Understanding varying levels of biodiversity within cities is pivotal to protect
      it in the face of global urbanisation. In the early stages of urban ecology
      studies on intra-urban biodiversity focused on the urban-rural gradient,
      representing a broad generalisation of features of the urban landscape.
      Increasingly, studies classify the urban landscape in more detail, quantifying
      separately the effects of individual urban features on biodiversity levels.
      However, while separate factors influencing biodiversity variation among cities
      worldwide have recently been analysed, a global analysis on the factors
      influencing biodiversity levels within cities is still lacking. We here present
      the first meta-analysis on intra-urban biodiversity variation across a large
      variety of taxonomic groups of 75 cities worldwide. Our results show that patch
      area and corridors have the strongest positive effects on biodiversity,
      complemented by vegetation structure. Local, biotic and management habitat
      variables were significantly more important than landscape, abiotic or design
      variables. Large sites greater than 50 ha are necessary to prevent a rapid loss
      of area-sensitive species. This indicates that, despite positive impacts of
      biodiversity-friendly management, increasing the area of habitat patches and
      creating a network of corridors is the most important strategy to maintain high
      levels of urban biodiversity. 

PMID- 25865807
TI  - Erratum to: Lactic acid bacteria--20 years exploring their potential as live
      vectors for mucosal vaccination.

PMID- 25865806
TI  - Effect of dietary fish oil on the expression of genes involved in lipid
      metabolism in liver and skeletal muscle of lactating sows.
AB  - This study investigated the hypothesis that dietary supplementation of fish oil
      as a source of n-3 polyunsaturated fatty acids (PUFA) influences the expression
      of target genes of sterol regulatory element-binding proteins (SREBP)-1 and
      (SREBP)-2 involved in triacylglycerol (TAG) synthesis and fatty acid and
      cholesterol metabolism in the liver, and moreover activates the expression of
      target genes of peroxisome proliferation-activated receptor (PPAR)-alpha involved
      in TAG and fatty acid catabolism in liver and skeletal muscle. Twenty lactating
      sows were fed a control diet or a fish oil diet with either 50 g of a mixture of
      palm oil and soya bean oil (4:1, w/w) or fish oil per kg. The diet of the fish
      oil group contained 19.1 g of n-3 PUFA (mainly 20:5 n-3 and 22:6 n-3) per 100 g
      of total fatty acids, while the diet of the control group contained 2.4 g of n-3
      PUFA (mainly 18:3 n-3) per 100 g of total fatty acids. The fish oil group had
      reduced relative mRNA concentrations of various target genes of SREBP-1 involved
      in fatty acid and TAG synthesis in comparison with the control group (p < 0.05).
      Relative mRNA concentrations of target genes of PPARalpha involved in fatty acid
      catabolism in both liver and muscle, and mRNA concentrations of target genes of
      SREBP-2 involved in cholesterol synthesis and uptake were not influenced by fish
      oil supplementation. Concentrations of cholesterol and TAG in plasma, fat content
      of milk and weight gains of litters during the suckling period were not different
      between the two groups of sows. In conclusion, this study suggests that fish oil
      has only minor effects on hepatic lipid metabolism, which are non-critical with
      respect to milk production in sows. 

PMID- 25865808
TI  - Serum biochemical reference intervals for free-living Sand Tiger sharks
      (Carcharias taurus) from east Australian waters.
AB  - BACKGROUND: Sharks are top-order predators in ocean food chains and the star
      attractions in aquaria worldwide. Unfortunately, blood biochemistry reference
      intervals (RI) have been determined for few species. OBJECTIVE: The study aims to
      establish serum biochemical RI for free-living Sand Tiger sharks (Carcharias
      taurus) off eastern Australia. METHODS: Thirty-seven sharks were captured and
      their sex, length, weight, reproductive maturity, and health status were
      recorded. After blood collection, serum analytes were quantified using standard
      analytical and statistical methods. Reference intervals, means, medians, and 90%
      confidence intervals were generated. Physiologic data from live and necropsied
      sharks were used to enhance the study results. RESULTS: Thirty healthy sharks
      were included in the study. Albumin could not be detected. With the exception of
      ALP activity, values were unaffected by sex, length, weight, age, and life
      history stage. The means (RI) were: sodium 258 (249-267) mmol/L, potassium 5.0
      (4.3-5.7) mmol/L, chloride 242 (227-257) mmol/L, inorganic phosphate 1.8 (1.7
      2.0) mmol/L, total calcium 3.9 (3.3-4.4) mmol/L, magnesium 1.9 (1.6-2.2) mmol/L,
      glucose 2.7 (2.2-3.2) mmol/L, urea 377 (360-394) mmol/L, ALP 20 (8-31) U/L, ALT 3
      U/L (no RI), AST 29 (13-45) U/L, CK 42 (5-79) U/L, total protein 30 (24-36) g/L,
      triglyceride 0.3 (0.1-0.6) mmol/L, cholesterol 1.4 (0.9-2.1) mmol/L, creatinine
      32 MUmol/L (no RI), total bilirubin 1.5 MUmol/L (no RI), and osmolarity 1082
      (1027-1136) mmol/L. CONCLUSIONS: These preliminary RI will assist with the
      clinical evaluation and treatment of captive and free-living Sand Tiger sharks
      worldwide. Studies with more animals will increase the precision of upper and
      lower reference limits.

PMID- 25865809
TI  - Nutrient input influences fungal community composition and size and can stimulate
      manganese (II) oxidation in caves.
AB  - Little is known about the fungal role in biogeochemical cycling in oligotrophic
      ecosystems. This study compared fungal communities and assessed the role of
      exogenous carbon on microbial community structure and function in two southern
      Appalachian caves: an anthropogenically impacted cave and a near-pristine cave.
      Due to carbon input from shallow soils, the anthropogenically impacted cave had
      an order of magnitude greater fungal and bacterial quantitative-polymerase chain
      reaction (qPCR) gene copy numbers, had significantly greater community diversity,
      and was dominated by ascomycotal phylotypes common in early phase, labile organic
      matter decomposition. Fungal assemblages in the near-pristine cave samples were
      dominated by Basidiomycota typically found in deeper soils (and/or in late phase,
      recalcitrant organic matter decomposition), suggesting more oligotrophic
      conditions. In situ carbon and manganese (II) [Mn(II)] addition over 10 weeks
      resulted in growth of fungal mycelia followed by increased Mn(II) oxidation. A
      before/after comparison of the fungal communities indicated that this enrichment
      increased the quantity of fungal and bacterial cells, yet decreased overall
      fungal diversity. Anthropogenic carbon sources can therefore dramatically
      influence the diversity and quantity of fungi, impact microbial community
      function, and stimulate Mn(II) oxidation, resulting in a cascade of changes that
      can strongly influence nutrient and trace element biogeochemical cycles in karst
      aquifers. 

PMID- 25865810
TI  - A Prospective, Longitudinal Study of Outcomes Following Total Knee Arthroplasty
      Stratified by Gender.
AB  - This study aimed to compare temporal trends in outcomes between men and women
      following TKA. A database of 272 TKAs at 7 years follow-up were evaluated for
      survivorship, functional, activity, and quality of life outcomes. Evaluation of
      implant survivorship, KSS scores, and ROM showed no significance differences
      between men and women, but both functional KSS scores and LEAS showed that men
      had significantly higher functional scores. The SF-36 physical component was
      found to be significantly better in men at multiple time points, whereas, the
      mental component was significantly better in men at pre-operative and 2 years.
      Both men and women benefit from TKA, however, men have higher levels of function
      and activity both prior to and after TKA than women. 

PMID- 25865811
TI  - Effect of Polyethylene Crosslinking and Bearing Design on Wear of
      Unicompartmental Arthroplasty.
AB  - Wear and polyethylene damage continue to be important factors affecting outcomes
      of unicompartmental knee arthroplasty. We compared two design rationales for
      unicompartmental arthroplasty: fully congruent mobile bearings; or moderately
      conforming fixed bearings using experimental and computational wear simulation.
      Experimental wear rates were 3.89 (+/-0.12) mg/million cycles for the highly
      crosslinked Triathlon PKR fixed bearing compared to 18.35 (+/-0.19) mg/million
      cycles for the low crosslinked Oxford mobile bearing. Finite element analysis was
      used to calculate the effect of crosslinking and backside wear. Increase in
      polyethylene crosslinking reduced wear by 68% while backside wear comprised 46%
      of the total wear in the mobile bearing. Increasing conformity may not be the
      sole predictor of wear performance and highly crosslinked fixed-bearing
      polyethylene insert can also provide high wear performance. 

PMID- 25865812
TI  - Contemporary Concepts in the Young Adult Hip Patient: Periacetabular Osteotomy
      for Hip Dysplasia.
AB  - The Bernese periacetabular osteotomy, as originally described by Dr. Reinhold
      Ganz, is an effective treatment for symptomatic acetabular dysplasia in the pre
      arthritic young adult hip. This technique has experienced several recent
      modifications in an attempt to optimize the clinical outcomes of these patients.
      We will review the clinical presentation of acetabular dysplasia, indications for
      surgery, contemporary refinements in technique and clinical results following
      periacetabular osteotomy. In well-selected patients, this reconstructive
      osteotomy should be considered safe and effective in alleviating pain and
      improving hip function. 

PMID- 25865813
TI  - The Cost-Utility of Total Hip Arthroplasty: Earlier Intervention, Improved
      Economics.
AB  - We estimated the cost of Quality-Adjusted-Life-Years gained according to
      preoperative disease severity. We studied 159 primary unilateral THA, mean follow
      up: 4 years. A median split of preoperative WOMAC scores was done to set apart a
      low (better) and a high (worse) score group. The groups with worse preoperative
      WOMAC were consistently associated with a less cost-effective intervention. The
      highest mean cost-effectiveness was achieved by patients with better WOMAC-total
      ($8256.32/QALY-gained). As patients aged, the cost-effectiveness of THA
      decreased. Patients 75 years of age or older and with worse scores had the least
      cost-effective interventions ($25,937.33/QALY-gained). THA remains a very cost
      effective intervention even when performed in older "sicker" patients. Waiting
      for the patient to deteriorate will make the intervention more "expensive".

PMID- 25865814
TI  - Does Co-Existing Lumbar Spinal Canal Stenosis Impair Functional Outcomes and
      Activity Levels after Primary Total Hip Arthroplasty?
AB  - Degenerative lumbar spinal stenosis (LSS) is a cause for substantial morbidity in
      the elderly population: many often undergo total hip arthroplasty for associated
      hip arthritis. With a matched cohort we investigated the effect of co-existing
      LSS on aseptic survivorship, functional outcomes, activity levels, overall
      subjective physical and mental health status, and satisfaction rates in patients
      undergoing primary THA. The aseptic-implant survivorship was similar in LSS and
      non-stenosis cohort. Although both cohorts significantly improved, the LSS cohort
      achieved lower improvements in HHS, UCLA, SF-36 physical, and satisfaction rates
      than the matched non-stenotic cohort. Surgeons should consider cautioning
      patients with LSS that although they can expect relief of their arthritic
      symptoms following THA, they may continue to expect limitations in function,
      physical-status, activity-levels, and satisfaction rates. 

PMID- 25865815
TI  - Quantifying the Burden of Revision Total Joint Arthroplasty for Periprosthetic
      Infection.
AB  - Periprosthetic joint infection (PJI) represents substantial clinical and economic
      burdens. This study evaluated patient and procedure characteristics and resource
      utilization associated with revision arthroplasty for PJI. The Nationwide
      Inpatient Sample (Q4 2005-2010) was analyzed for 235,857 revision THA (RTHA) and
      301,718 revision TKA (RTKA) procedures. PJI was the most common indication for
      RTKA, and the third most common reason for RTHA. PJI was most commonly associated
      with major severity of illness (SOI) in RTHA, and with moderate SOI in RTKA. RTHA
      and RTKA for PJI had the longest length of stay. Costs were higher for RTHA/RTKA
      for PJI than for any other diagnosis except periprosthetic fracture.
      Epidemiologic differences exist in the rank, severity and populations for RTHA
      and RTKA for PJI.

PMID- 25865816
TI  - Assessment of mitochondrial functions in Daphnia pulex clones using high
      resolution respirometry.
AB  - The objectives of our study were to adapt a method to measure mitochondrial
      function in intact mitochondria from the small crustacean Daphnia pulex and to
      validate if this method was sensitive enough to characterize mitochondrial
      metabolism in clones of the pulex complex differing in ploidy levels,
      mitochondrial DNA haplotypes, and geographic origins. Daphnia clones belonging to
      the Daphnia pulex complex represent a powerful model to delineate the link
      between mitochondrial DNA evolution and mitochondrial phenotypes, as single
      genotypes with divergent mtDNA can be grown under various experimental
      conditions. Our study included two diploid clones from temperate environments and
      two triploid clones from subarctic environments. The whole animal
      permeabilization and measurement of respiration with high-resolution respirometry
      enabled the measurement of the functional capacity of specific mitochondrial
      complexes in four clones. When expressing the activity as ratios, our method
      detected significant interclonal variations. In the triploid subarctic clone from
      Kuujjurapik, a higher proportion of the maximal physiological oxidative
      phosphorylation (OXPHOS) capacity of mitochondria was supported by complex II,
      and a lower proportion by complex I. The triploid subarctic clone from Churchill
      (Manitoba) showed the lowest proportion of the maximal OXPHOS supported by
      complex II. Additional studies are required to determine if these differences in
      mitochondrial functions are related to differences in mitochondrial haplotypes or
      ploidy level and if they might be associated with fitness divergences and
      therefore selective value.

PMID- 25865817
TI  - Racial and ethnic disparities in access to and utilization of living donor liver
      transplants.
AB  - Living donor liver transplantation (LDLT) is a comparable alternative to deceased
      donor liver transplantation and can mitigate the risk of dying while waiting for
      transplant. Although evidence exists of decreased utilization of living donor
      kidney transplants among racial minorities, little is known about access to LDLT
      among racial/ethnic minorities. We used Organ Procurement and Transplantation
      Network/United Network for Organ Sharing data from February 27, 2002 to June 4,
      2014 from all adult liver transplant recipients at LDLT-capable transplant
      centers to evaluate differential utilization of LDLTs based on race/ethnicity. We
      then used data from 2 major urban transplant centers to analyze donor inquiries
      and donor rule-outs based on racial/ethnic determination. Nationally, of 35,401
      total liver transplant recipients performed at a LDLT-performing transplant
      center, 2171 (6.1%) received a LDLT. In multivariate generalized estimating
      equation models, racial/ethnic minorities were significantly less likely to
      receive LDLTs when compared to white patients. For cholestatic liver disease, the
      odds ratios of receiving LDLT based on racial/ethnic group for African American,
      Hispanic, and Asian patients compared to white patients were 0.35 (95% CI, 0.20
      0.60), 0.58 (95% CI, 0.34-0.99), and 0.11 (95% CI, 0.02-0.55), respectively. For
      noncholestatic liver disease, the odds ratios by racial/ethnic group were 0.53
      (95% CI, 0.40-0.71), 0.78 (95% CI, 0.64-0.94), and 0.45 (95% CI, 0.33-0.60)
      respectively. Transplant center-specific data demonstrated that African American
      patients received fewer per-patient donation inquiries than white patients,
      whereas fewer African American potential donors were ruled out for obesity. In
      conclusion, racial/ethnic minorities receive a disproportionately low percentage
      of LDLTs, due in part to fewer initial inquiries by potential donors. This
      represents a major inequality in access to a vital health care resource and
      demands outreach to both patients and potential donors.

PMID- 25865818
TI  - Lutetium-177 therapeutic radiopharmaceuticals: linking chemistry, radiochemistry,
      and practical applications.

PMID- 25865820
TI  - c-Fos is involved in inhibition of human bladder carcinoma T24 cells by brazilin.
AB  - Crude brazilin extract from Sappan wood has demonstrated strong anti tumor
      activity in the mouse model of human bladder carcinoma and clinical trial for
      intravesical therapy. Purified brazilin was confirmed the most active molecule in
      inhibition of bladder carcinoma T24 cells. Brazilin decreased proliferation and
      viability of T24 cells in a dose- and time-dependent manner, with a calculated
      LC50 of 32 ug/mL. More than 1,000 of genes were found upregulated and down
      regulated by brazilin treatment in digital gene expression profiling. Gene
      ontology analysis indicated that stress response, apoptosis, and cell cycle
      regulatory pathways were highly enriched. Among the regulated genes, c-Fos was
      the most and specifically upregulated. Overexpression of c-Fos in T24 cells
      resulted in tumor cell specific changes in cell morphology and viability. Over
      expression of stress-responsive gene, HSP70, and other highly upregulated genes
      did not have any effect on cell growth. Brazilin may inhibit T24 cell growth and
      trigger cell death through a c-Fos-mediated and tumor cell specific signaling
      pathway. Further studies of its down stream mediators may help to identify better
      tumor cell type specific drug targets.

PMID- 25865821
TI  - Valsalva hemorrhagic retinopathy presenting as a rare cause of impaired vision
      after a general anesthetic-a case report and review of the literature.
AB  - Postoperative visual loss from any cause is potentially catastrophic. We present
      a case of Valsalva hemorrhagic retinopathy (VHR) as a rare cause of impaired
      vision after an apparently uneventful general anesthetic. Previously published
      cases of VHR, anesthetic related and otherwise, are reviewed and the phenomenon
      discussed. Although VHR is considered to be rare, the events and activities with
      which it is associated are relatively common, both in everyday life and in the
      operating room. We suggest that the occurrence of VHR after anesthesia and
      surgery may be more frequent than previously appreciated and make recommendations
      for further investigations. 

PMID- 25865819
TI  - Polygenic risk for alcohol dependence associates with alcohol consumption,
      cognitive function and social deprivation in a population-based cohort.
AB  - Alcohol dependence is frequently co-morbid with cognitive impairment. The
      relationship between these traits is complex as cognitive dysfunction may arise
      as a consequence of heavy drinking or exist prior to the onset of dependence. In
      the present study, we tested the genetic overlap between cognitive abilities and
      alcohol dependence using polygenic risk scores (PGRS). We created two independent
      PGRS derived from two recent genome-wide association studies (GWAS) of alcohol
      dependence (SAGE GWAS: n = 2750; Yale-Penn GWAS: n = 2377) in a population-based
      cohort, Generation Scotland: Scottish Family Health Study (GS:SFHS) (n = 9863).
      Data on alcohol consumption and four tests of cognitive function [Mill Hill
      Vocabulary (MHV), digit symbol coding, phonemic verbal fluency (VF) and logical
      memory] were available. PGRS for alcohol dependence were negatively associated
      with two measures of cognitive function: MHV (SAGE: P = 0.009, beta = -0.027;
      Yale-Penn: P = 0.001, beta = -0.034) and VF (SAGE: P = 0.0008, beta = -0.036;
      Yale-Penn: P = 0.00005, beta = -0.044). VF remained robustly associated after
      adjustment for education and social deprivation; however, the association with
      MHV was substantially attenuated. Shared genetic variants may account for some of
      the phenotypic association between cognitive ability and alcohol dependence. A
      significant negative association between PGRS and social deprivation was found
      (SAGE: P = 5.2 * 10(-7) , beta = -0.054; Yale-Penn: P = 0.000012, beta = -0.047).
      Individuals living in socially deprived regions were found to carry more alcohol
      dependence risk alleles which may contribute to the increased prevalence of
      problem drinking in regions of deprivation. Future work to identify genes which
      affect both cognitive impairment and alcohol dependence will help elucidate
      biological processes common to both disorders.

PMID- 25865822
TI  - Alpha shape theory for 3D visualization and volumetric measurement of brain tumor
      progression using magnetic resonance images.
AB  - Resection of brain tumors is a tricky task in surgery due to its direct influence
      on the patients' survival rate. Determining the tumor resection extent for its
      complete information via-a-vis volume and dimensions in pre- and post-operative
      Magnetic Resonance Images (MRI) requires accurate estimation and comparison. The
      active contour segmentation technique is used to segment brain tumors on pre
      operative MR images using self-developed software. Tumor volume is acquired from
      its contours via alpha shape theory. The graphical user interface is developed
      for rendering, visualizing and estimating the volume of a brain tumor. Internet
      Brain Segmentation Repository dataset (IBSR) is employed to analyze and determine
      the repeatability and reproducibility of tumor volume. Accuracy of the method is
      validated by comparing the estimated volume using the proposed method with that
      of gold-standard. Segmentation by active contour technique is found to be capable
      of detecting the brain tumor boundaries. Furthermore, the volume description and
      visualization enable an interactive examination of tumor tissue and its
      surrounding. Admirable features of our results demonstrate that alpha shape
      theory in comparison to other existing standard methods is superior for precise
      volumetric measurement of tumor. 

PMID- 25865823
TI  - On the safety margin of using simplified human head models for local SAR
      simulations of B1-shimming at 7 Tesla.
AB  - PURPOSES: Using simplified human models significantly alleviates the difficulty
      of rendering human models for subject-specific local specific absorption rate
      (SAR) simulations. Although its accuracy has been demonstrated with the birdcage
      mode combination of RF transmitters, its accuracy in general B1-shimming, where
      numerous phase and magnitude combinations can take place, is yet unknown.
      METHODS: The electromagnetic fields of a 7-Tesla eight-channel brain imaging
      array were simulated by using four detailed human models from the Virtual Family
      and their two-, three-, and four-tissue simplifications. The 10-g averaged local
      SAR was computed for each case with 1,000 sets of uniformly distributed random B1
      shimming parameters. Linear regression was applied to relate the local SAR
      obtained by using detailed and simplified human models. The 99% confidence
      prediction interval was determined as the safety margin in order to cover the
      largest local SAR variability introduced by using simplified human models.
      RESULTS: The local SAR computed by using three- and four-tissue simplifications
      are strongly correlated with those computed by using detailed models. Safety
      margins of 0.38 and 0.45W/kg/W were found appropriate for each case being
      considered. CONCLUSIONS: The proposed procedure can be applied to evaluate the
      safety margin of the local SAR simulated by using simplified human models.
      However, discretion needs to be exercised since the safety margins in some cases
      may represent more than 50% overestimation.

PMID- 25865824
TI  - Evidence for IL-6/STAT3-independent induction of lipocalin-2 in the liver of mice
      infected with Escherichia coli.

PMID- 25865825
TI  - Reactivity of copper-alpha-synuclein peptide complexes relevant to Parkinson's
      disease.
AB  - Parkinson's disease (PD) is a neurodegenerative disorder characterized by the
      presence of abnormal alpha-synuclein (alphaSyn) deposits in the brain.
      Alterations in metal homeostasis and metal-induced oxidative stress may play a
      crucial role in the aggregation of alphaSyn and, consequently, in the
      pathogenesis of PD. We have therefore investigated the capability of copper
      alphaSyn6 and copper-alphaSyn15 peptide complexes, with the 1-6 and 1-15 terminal
      fragments of the protein, to promote redox reactions that can be harmful to other
      cellular components. The pseudo-tyrosinase activity of copper-alphaSyn complexes
      against catecholic (di-tert-butylcatechol (DTBCH2), 4-methylcatechol (4-MC)) and
      phenolic (phenol) substrates is lower compared to that of free copper(II). In
      particular, the rates (kcat) of DTBCH2 catalytic oxidation are 0.030 s(-1) and
      0.009 s(-1) for the reaction promoted by free copper(II) and [Cu(2+)-alphaSyn15],
      respectively. On the other hand, HPLC/ESI-MS analysis of solutions of alphaSyn15
      incubated with copper(II) and 4-MC showed that alphaSyn is competitively oxidized
      with remarkable formation of sulfoxide at Met1 and Met5 residues. Moreover, the
      sulfoxidation of methionine residues, which is related to the aggregation of
      alphaSyn, also occurs on peptides not directly bound to copper, indicating that
      external alphaSyn can also be oxidized by copper. Therefore, this study
      strengthens the hypothesis that copper plays an important role in oxidative
      damage of alphaSyn which is proposed to be strongly related to the etiology of
      PD.

PMID- 25865826
TI  - Composite polymer/oxide hollow fiber contactors: versatile and scalable flow
      reactors for heterogeneous catalytic reactions in organic synthesis.
AB  - Flexible composite polymer/oxide hollow fibers are used as flow reactors for
      heterogeneously catalyzed reactions in organic synthesis. The fiber synthesis
      allows for a variety of supported catalysts to be embedded in the walls of the
      fibers, thus leading to a diverse set of reactions that can be catalyzed in flow.
      Additionally, the fiber synthesis is scalable (e.g. several reactor beds
      containing many fibers in a module may be used) and thus they could potentially
      be used for the large-scale production of organic compounds. Incorporating
      heterogeneous catalysts in the walls of the fibers presents an alternative to a
      traditional packed-bed reactor and avoids large pressure drops, which is a
      crucial challenge when employing microreactors. 

PMID- 25865827
TI  - Preparation and characterization of glycoprotein-resistant starch complex as a
      coating material for oral bioadhesive microparticles for colon-targeted
      polypeptide delivery.
AB  - For effective oral delivery of polypeptide or protein and enhancement their oral
      bioavailability, a new resistant starch-glycoprotein complex bioadhesive carrier
      and an oral colon-targeted bioadhesive delivery microparticle system were
      developed. A glycoprotein, concanavalin A (Con A), was successfully conjugated to
      the molecules of resistant starch acetate (RSA), leading to the formation of
      resistant starch-glycoprotein complex. This Con A-conjugated RSA film as a
      coating material showed an excellent controlled-release property. In
      streptozotocin (STZ)-induced type II diabetic rats, the insulin-loaded
      microparticles coated with this Con A-conjugated RSA film exhibited good
      hypoglycemic response for keeping the plasma glucose level within the normal
      range for totally 44-52 h after oral administration with different insulin
      dosages. Oral glucose tolerance tests indicated that successive oral
      administration of these colon-targeted bioadhesive microparticles with insulin at
      a level of 50 IU/kg could achieve a hypoglycemic effect similar to that by
      injection of insulin at 35 IU/kg. Therefore, the potential of this new Con A
      conjugated RSA film-coated microparticle system has been demonstrated to be
      capable of improving the oral bioavailability of bioactive proteins and peptides.

PMID- 25865828
TI  - Effect of spacer chain length on the liquid structure of aqueous dicationic ionic
      liquid solutions: molecular dynamics studies.
AB  - The liquid structure of aqueous solutions of five different imidazolium based
      gemini dicationic ionic liquids 1,n-bis(3-methylimidazolium-1-yl) alkane bromide
      (n being the length of the spacer alkyl chain), with propyl, pentyl, octyl, decyl
      and hexadecyl spacer chains has been studied using atomistic molecular dynamics
      simulations. While solutions with propyl and pentyl spacers are homogeneous,
      those with octyl and decyl spacers show spatial heterogeneity. Microscopic
      inhomogeneity in the bulk solution phase increases with an increase in the length
      of the spacer chain leading to polydisperse aggregates in the solution with a
      hexadecyl spacer. Organization of the cations at the solution-vapor interface
      also depends upon the length of the spacer chain with the most organized
      interfacial layer observed in the solution with a hexadecyl spacer chain. 

PMID- 25865830
TI  - Family-style dining on a child and adolescent psychiatry unit: a quality
      improvement project to reduce weight changes in patients.
AB  - BACKGROUND: Improving nutritional standards for children has become a national
      health initiative. However, children who are hospitalized are often at additional
      risk for poor nutrition and diet. Following a change to family-style dining,
      nursing staff noted significant patient weight changes. We undertook a quality
      improvement project to address this issue and promote healthy weight maintenance.
      METHODS: Nursing staff requested changes to the types of foods served and placed
      limits on how much patients were permitted to eat. We also developed a nutrition
      group to educate the patients on healthy food choices. RESULTS: We were able to
      reduce weight changes in patients on our unit from a mean change of 2.5 kg (5.5
      lb) to a mean change of 0.01 kg (0.027 lb). CONCLUSIONS: Patient education,
      healthy food offerings, and limiting the amount of food eaten at meals had
      positive outcomes on patient weights during a child and adolescent psychiatry
      hospitalization.

PMID- 25865829
TI  - Beyond Comorbidity: A Critical Perspective of Syndemic Depression and Diabetes in
      Cross-cultural Contexts.
AB  - This article examines the comorbidity concept in medical anthropology. I argue
      that the dearth of articles on comorbidity in medical anthropology may result
      from the rise of syndemic theory. Syndemics recognize how social realities shape
      individual illness experiences as well as distribution of diseases across
      populations. I discuss synergistic interactions foundational to the syndemics
      construct through my research of depression and diabetes comorbidity in
      vulnerable populations from urban United States, India, and South Africa. I argue
      that social and economic factors that cluster with depression and diabetes alone
      and together exemplify the biosocial processes that are at the heart of
      syndemics. In doing so, I illustrate how social, cultural, and economic factors
      shape individual-level experiences of co-occurring diseases despite similar
      population-level trends. Finally, I discuss the relevance of syndemics for the
      fields of medicine and public health while cautioning what must not be lost in
      translation across disciplines.

PMID- 25865832
TI  - Suspicious macroscopic features of small malignant colorectal polyps.
AB  - OBJECTIVE: The aim of this analysis was to retrospectively review video
      recordings of malignant polyps <10 mm in search for suspicious macroscopic
      features in white light endoscopy. METHODS: Database entries and recordings of
      screening colonoscopies from a single tertiary referral center between June 2009
      and December 2012 were reviewed. Malignant polyps <10 mm were analyzed. The
      recordings were reviewed by two expert endoscopists in search for suspicious
      morphological features: irregular contours, central depression, contact bleeding,
      shape deformity, central depression, chicken skin sign, circumscribed area with
      abnormal vascular and/or surface pattern. Then, six experienced endoscopists
      watched the recordings in search of listed features. Next, video recordings of
      these malignant polyps were mixed with randomly drawn video recordings of 20 non
      malignant polyps matched by size and reviewed by 14 blinded endoscopists to
      assess the sensitivity and specificity for the diagnosis of malignant polyps.
      RESULTS: Five of the 8651 (0.06%) subjects who underwent screening colonoscopy
      during the study period were diagnosed with a malignant polyp <10 mm. Only one of
      them was ad hoc identified by performing endoscopist as suspicious. On recordings
      review performed by the experts, each of the four remaining polyps presented at
      least one suspicious macroscopic feature. Presence of these features was
      confirmed by experienced endoscopists. The sensitivity and specificity for the
      diagnosis of malignant polyp were 73.21% and 85.35%, respectively, if at least
      two suspicious macroscopic features defined malignant polyp. CONCLUSIONS: On
      careful white light endoscopy examination small malignant colorectal polyps show
      suspicious macroscopic features, which were frequently unrecognized by examining
      endoscopists.

PMID- 25865831
TI  - Drebrin depletion alters neurotransmitter receptor levels in protein complexes,
      dendritic spine morphogenesis and memory-related synaptic plasticity in the mouse
      hippocampus.
AB  - Drebrin an actin-bundling key regulator of dendritic spine genesis and
      morphology, has been recently proposed as a regulator of hippocampal
      glutamatergic activity which is critical for memory formation and maintenance.
      Here, we examined the effects of genetic deletion of drebrin on dendritic spine
      and on the level of complexes containing major brain receptors. To this end,
      homozygous and heterozygous drebrin knockout mice generated in our laboratory and
      related wild-type control animals were studied. Level of protein complexes
      containing dopamine receptor D1/dopamine receptor D2, 5-hydroxytryptamine
      receptor 1A (5-HT1(A)R), and 5-hydroxytryptamine receptor 7 (5-HT7R) were
      significantly reduced in hippocampus of drebrin knockout mice whereas no
      significant changes were detected for GluR1, 2, and 3 and NR1 as examined by
      native gel-based immunoblotting. Drebrin depletion also altered dendritic spine
      formation, morphology, and reduced levels of dopamine receptor D1 in dendritic
      spines as evaluated using immunohistochemistry/confocal microscopy.
      Electrophysiological studies further showed significant reduction in memory
      related hippocampal synaptic plasticity upon drebrin depletion. These findings
      provide unprecedented experimental support for a role of drebrin in the
      regulation of memory-related synaptic plasticity and neurotransmitter receptor
      signaling, offer relevant information regarding the interpretation of previous
      studies and help in the design of future studies on dendritic spines.

PMID- 25865833
TI  - Support vector machine classification of brain metastasis and radiation necrosis
      based on texture analysis in MRI.
AB  - PURPOSE: To develop a classification model using texture features and support
      vector machine in contrast-enhanced T1-weighted images to differentiate between
      brain metastasis and radiation necrosis. METHODS: Texture features were extracted
      from 115 lesions: 32 of them previously diagnosed as radiation necrosis, 23 as
      radiation-treated metastasis and 60 untreated metastases; including a total of
      179 features derived from six texture analysis methods. A feature selection
      technique based on support vector machine was used to obtain a subset of features
      that provide optimal performance. RESULTS: The highest classification accuracy
      evaluated over test sets was achieved with a subset of ten features when the
      untreated metastases were not considered; and with a subset of seven features
      when the classifier was trained with untreated metastases and tested on treated
      ones. Receiver operating characteristic curves provided area-under-the-curve
      (mean +/- standard deviation) of 0.94 +/- 0.07 in the first case, and 0.93 +/-
      0.02 in the second. CONCLUSION: High classification accuracy (AUC > 0.9) was
      obtained using texture features and a support vector machine classifier in an
      approach based on conventional MRI to differentiate between brain metastasis and
      radiation necrosis.

PMID- 25865834
TI  - A model for a positive youth development intervention.
AB  - Modern-day life necessitates the application of interventions to facilitate the
      development of the youth in a more positive trajectory. Lacunae in the Positive
      Youth Development (PYD) paradigm include, inter alia, the lack of integration
      between theory and application and a lack of exposition of the processes
      underlying developmental change in the youth. The aim of this study was to
      develop a theoretical model to facilitate the development of youth in early
      adolescence. The proposed model builds on existing models, namely the
      Phenomenological Variant of Ecological Systems Theory and the Selection
      Optimization and Compensation (SOC) model. A review of the literature on the PYD
      paradigm and other areas of psychology with a similar strength-based focus,
      yielded theory which could be used to expand on the basic framework. The
      resulting Positive Youth Development Intervention model (PYDI) is described with
      reference to meta-theoretical assumptions, theoretical hypotheses, and constructs
      referring to phenomena and processes to be facilitated on an empirical level.
      This model can be operationalised to develop an intervention which can then be
      evaluated, thereby contributing to bridging theory and application in PYD. 

PMID- 25865835
TI  - The theory of planned behaviour as a framework for predicting sexual risk
      behaviour in sub-Saharan African youth: A critical review.
AB  - Amongst the psychological theories that have been used to help understand why
      people have unprotected sex, the Theory of Planned Behaviour (TPB: Ajzen 1991)
      has earned a prominent position. This article is a critical review of 11 peer
      reviewed studies conducted in sub-Saharan Africa during 2001 to 2009, which used
      the TPB as a model of predicting sexual risk behaviour in young people. All the
      studies revealed the predictive ability of the TPB in urban, rural, and
      traditional African settings, with R (2) coefficients ranging between 0.14 and
      0.67. With data comparing favourably to those obtained in the international
      literature, these studies indicate that the TPB can be used to study sexual risk
      intentions and behaviour in sub-Saharan African youth, and question arguments
      against the theory's use in non-Western settings. 

PMID- 25865836
TI  - Correlates of heavy alcohol consumption at Rhodes University.
AB  - OBJECTIVE: To establish the extent to which students typically overestimate
      normative drinking and to determine whether these estimates are uniquely
      implicated in alcohol consumption over and above the role of the various
      demographic and family variables. METHOD: An online survey was used to obtain a
      sample of 2 177 students who completed the AUDIT questionnaire along with other
      items, including three adapted from the AUDIT asking respondents to estimate the
      descriptive drinking norms of their typical same-sex student. A hierarchical
      regression analysis was performed to determine the relative contributions of
      these variables towards individual student's own consumption scores. Three blocks
      of variables were entered in temporal sequence, starting with demographic
      variables, then family variables, followed by the normative estimates. RESULTS:
      Most students overestimate how frequently their same-sex peers go drinking and
      how much alcohol they consume on these drinking occasions and how often they
      consume six or more drinks on one occasion. These normative estimates account for
      a significant portion of the variance over and above that accounted for by the
      demographic and family variables. CONCLUSIONS: The university should attempt to
      correct inflated normative estimates of how many drinks a typical same-sex peer
      has on a typical day when drinking.

PMID- 25865837
TI  - The influence of psychosocial variables on adolescent suicidal ideation.
AB  - BACKGROUND: Increased rates of suicide among adolescents aged 15-24 years have
      led to suicides becoming the third leading cause of death in the Unites States.
      South African statistics show an equally worrying trend as suicide constitutes
      11.5% of the total deaths for the age group 11-20 years (Stark et al. 2010). A
      national youth risk behaviour survey done in South Africa has re-emphasised the
      need for concern, as adolescent suicidal behaviour increased between 2002 and
      2008 (Reddy et al. 2010). The objective was to investigate the influence of risk
      and protective factors (psychosocial and individual factors) on suicidal
      ideation. The Integrated Stress and Coping Process model was used as guiding
      theory for the inclusion of personal and contextual stressors and resources
      including coping strategies as potential risk and protective factors, in their
      relationship to suicidal ideation. METHOD: A purposive, stratified sampling
      technique was used to study 381 adolescents in the Northern Cape Province. The
      instruments used were a suicidal ideation questionnaire; a biographical
      questionnaire; a self-esteem scale; and a survey examining stressors and
      resources relevant to adolescents. RESULTS: Suicidal ideation was significantly
      higher in the South African sample than in an American sample. Avoidant coping
      strategies (denial, emotional venting and restraint coping), negative life events
      and stressful romantic relationships contributed to higher levels of suicidal
      ideation while self-esteem and adaptive coping (acceptance and seeking social
      support for instrumental reasons) reduced these levels. CONCLUSION: A lack of
      self-esteem, ineffective coping and particular stressors contributed
      significantly to the vulnerability of adolescents. Future studies should explore
      a wider range of dispositional factors that influence effective coping and
      adjustment in addressing adolescent suicidal ideation.

PMID- 25865838
TI  - Emotional and behavioural barriers to learning and development in the inclusive
      education classrooms in South Africa: Developing a training programme for
      teachers.
AB  - OBJECTIVE: The interaction between teachers, classroom strategies and learners
      experiencing emotional and behavioural barriers to learning and development in a
      system of inclusive education results in multiple dynamics on different levels.
      Many teachers in mainstream education lack training to deal with learners
      experiencing emotional and behavioural barriers. Resistance towards inclusive
      education is therefore evident. This paper describes the process of developing an
      in-service training programme for teachers who deal with learners with emotional
      and behavioural barriers in their classrooms. METHOD: A process of action
      research was used to allow the researcher, in collaboration with 47 teachers from
      2 primary schools, to develop a training programme to address the specific needs
      of teachers in dealing with learners experiencing emotional and behavioural
      barriers in their classes. Qualitative feedback from teachers and observations by
      the researcher and external observers were used to evaluate the appropriateness
      of the training. FINDINGS: Teachers experienced that appropriate classroom
      management strategies made a significant difference in the behaviour of learners
      experiencing emotional and behavioural barriers. The training affected teachers'
      attitudes, teacher-learner interaction, learner behaviour and school
      organisation. CONCLUSION: In-service training for teachers can affect the
      effective implementation of inclusive education. This programme can be adapted to
      address the needs of teachers in other areas.

PMID- 25865839
TI  - The development of psychoanalytic parent-infant/child psychotherapy in South
      Africa: Adaptive responses to contextual challenges.
AB  - South African authored writings on psychoanalytically-informed parent
      infant/child psychotherapy are rare, but this dearth does not accurately reflect
      the extent of practice in the country at the community, public and private
      levels. Interviews with a sample of key stakeholders and practitioners provided
      information on different services currently offered in the South African parent
      infant/child psychotherapy field. Three major themes were identified during an
      analysis of interview material: the role of language and culture; the issue of
      training; and the challenge of working outside of a national health system.
      Interviewees also described adaptive responses to these contextual challenges.
      These responses are discussed as evidence of the usefulness of theoretical and
      technical eclecticism, when applied with psychoanalytic mindfulness, in
      developing the South African parent-infant/child psychotherapy field. 

PMID- 25865840
TI  - Spiritual well-being and lifestyle choices in adolescents: A quantitative study
      among Afrikaans-speaking learners in the North West Province of South Africa.
AB  - OBJECTIVE: This article reports on an investigation into the connection between
      spirituality and the lifestyle choices of adolescents in the North West Province
      of South Africa. METHOD: An examination of the theoretical connections between
      these two entities in the lives of adolescents was followed by a quantitative
      study in which a questionnaire consisting of an adapted version of the Youth Risk
      Behaviour Survey and the Spiritual Well-Being Scale was used. RESULTS: The
      empirical investigation shows that a significant correlation exists between the
      two variables and it appears that spiritual well-being can have a positive
      influence on the lifestyle choices made by adolescents. CONCLUSION: Further
      research must be carried out to assess the impact of spirituality on risk
      behaviours and lifestyle choices.

PMID- 25865841
TI  - Treating borderline personality disorder as a trainee psychologist: Issues of
      resistance, inexperience and countertransference.
AB  - Clients with borderline personality disorder are viewed as difficult to work
      with. They also have high drop-out rates and unpredictable treatment outcomes.
      The characteristics of patients with borderline personality disorder often have a
      negative effect on the therapeutic process and on clinicians themselves.
      Challenges are likely magnified for trainee psychologists, given their lack of
      experience in implementing treatment plans and their inadequate understanding of
      underlying dynamics. However, to date, no studies have focused on the particular
      challenges experienced by trainee psychologists. This article attempts to address
      the gap in literature by exploring the difficulties experienced by a trainee
      psychologist in treating a patient with borderline personality disorder. A case
      study is used to highlight the challenges experienced by a novice psychologist in
      using specific therapeutic modalities recommended in the treatment of borderline
      personality disorder (BPD), namely dialectical behaviour therapy (DBT) and
      mentalisation based therapy (MBT). The aim of the study was to help better
      identify, understand and normalise the countertransference experiences and other
      difficulties experienced by trainee psychologists in treating clients with BPD.
      The article highlights observations regarding the context of the supervisory
      process, the importance of personal psychotherapy, the potential for harm of
      pejorative views, and the complications arising from a mismatch between the
      treatment modality and the treatment context. 

PMID- 25865842
TI  - Reading winnicott.

PMID- 25865843
TI  - Journal abstracts from current research in the field of child and adolescent
      mental health.

PMID- 25865845
TI  - Dual diagnosis in adolescence - An escalating health risk.

PMID- 25865846
TI  - Discovery of 4-acetyl-3-(4-fluorophenyl)-1-(p-tolyl)-5-methylpyrrole as a dual
      inhibitor of human P-glycoprotein and Staphylococcus aureus Nor A efflux pump.
AB  - Polysubstituted pyrrole natural products, lamellarins, are known to overcome
      multi-drug resistance in cancer via the inhibition of p-glycoprotein (P-gp) and
      breast cancer resistance protein (BCRP) efflux pumps. Herein, a series of
      simplified polysubstituted pyrroles, prepared via a one-pot domino protocol, were
      screened for P-gp inhibition in P-gp overexpressing human adenocarcinoma LS-180
      cells using a rhodamine 123 efflux assay. Several compounds showed the
      significant inhibition of P-gp at 50 MUM, as indicated by increase in the
      intracellular accumulation of Rh123 in LS-180 cells. Furthermore, pyrrole 5i
      decreased the efflux of digoxin, a FDA approved P-gp substrate in MDCK-MDR1 cells
      with an IC50 of 11.2 MUM. In in vivo studies, following the oral administration
      of a P-gp substrate drug, rifampicin, along with compound , the Cmax and AUC0
      infinity of rifampicin was enhanced by 31% and 46%, respectively. All the
      compounds were then screened for their ability to potentiate ciprofloxacin
      activity via the inhibition of Staphylococcus aureus Nor A efflux pump. Pyrrole
      showed the significant inhibition of S. aureus Nor A efflux pump with 8- and 4
      fold reductions in the MIC of ciprofloxacin at 50 and 6.25 MUM, respectively. The
      molecular docking studies of compound with the human P-gp and S. aureus Nor A
      efflux pump identified its plausible binding site and key interactions. Thus, the
      results presented herein strongly indicate the potential of this scaffold for its
      use as multi-drug resistance reversal agent or bioavailability enhancer. 

PMID- 25865847
TI  - Prehospital Pain and Analgesic Therapy in Elderly Patients with Hip Fractures.
AB  - INTRODUCTION: As a part of aging, hip fractures are becoming more common. The
      connection between increased pain and a poor outcome has previously been shown.
      Therefore, even in prehospital situations, analgesic therapy appears to be
      reasonable. We established a prospective study with 153 patients to evaluate the
      patients' pain levels during the prehospital phase of treatment and prehospital
      analgesic therapy. METHODS: We performed a prospective study on 153 patients the
      age of 60 years or older in a University hospital setting between 2010 and 2011
      who suffered hip fracture. Analgesics given and the type of medical staff that
      was involved were documented. Pain was measured using the NRS upon initial
      contact of the medical staff and upon admission to our emergency department.
      RESULTS: Initial pain level evaluated by EMS (emergency medical service) was 6.8
      (SD = 2.7). Twenty-two percent of the patients reported an NRS of 10 as the
      highest value following their injury. Forty-three of 153 patients (28%) received
      analgesics. The mean initial pain score for those 43 patients who did receive
      pain medication was 7.0 (SD = 2.6). However, this score dropped to a mean of 2.8
      (SD = 1.4) upon hospital arrival (P < 0.001). The patients who did not receive
      pain medication had an initial pain score of 4.5 (SD = 1.9). Upon admission to
      the hospital, this score decreased to a mean of 4.0 (SD = 1.7, P = 0.092).
      CONCLUSION: Only a minority of patients with hip fractures received prehospital
      analgesia. The administration of prehospital analgesia was associated with
      significant pain relief.

PMID- 25865848
TI  - Testosterone replacement therapy and the risk of prostate cancer.
AB  - Understanding the role of testosterone replacement therapy (TRT) in the
      development and progression of prostate cancer is an important concept in
      treating patients with symptoms of hypogonadism. This article revealed a small
      number of mostly retrospective, observational studies describing the use of TRT
      in the general population, in men with prostatic intraepithelial neoplasia (PIN),
      in men with a history of treated prostate cancer, and in men on active
      surveillance for prostate cancer. The current literature does not report a
      statistically significant increase in the development or progression of prostate
      cancer in men receiving testosterone replacement for symptomatic hypogonadism,
      and the prostate saturation theory provides a model explaining the basis for
      these results. The use of TRT in men with a history of prostate cancer is
      considered experimental, but future results from randomized controlled trials
      could lead to a change in our current treatment approach. 

PMID- 25865849
TI  - Therapy decisions for the symptomatic patient with metastatic castration
      resistant prostate cancer.
AB  - Metastatic prostate cancer continues to kill approximately 30,000 men per year.
      Since 2010, five new therapeutic agents have been Food and Drug Administration
      (FDA) approved to treat metastatic castration-resistant prostate cancer (mCRPC).
      With the increasing number of therapies available to clinicians, the most
      effective sequence in which to implement these treatments remains unknown. The
      presence or absence of symptoms (i.e., bony pain, visceral crisis) is a key
      parameter that informs the decision-making process regarding therapy. Treatment
      algorithms based on: 1) asymptomatic/minimal symptoms, 2) moderate symptoms or
      chemotherapy ineligible or 3) symptomatic disease need to be developed.

PMID- 25865851
TI  - The mitochondrial genome of Spualiobarbus curriculus of Pearl River.
AB  - Spualiobarbus curriculus is an important economic species in China. In this
      study, the complete mitochondrial genome of S. curriculus collected from three
      parts of Pearl River is cloned and analyzed. The complete sequence includes 22
      tRNA genes, two rRNA genes, 13 protein-coding genes, and a D-loop region. The
      composition of nucleic acid is calculated and it is similar to the known S.
      curriculus mtDNA. The diversities of sequences and the phylogenetic tree approve
      that there is high similarity with the one of Yangtze, but there is geographic
      differences between the sequences. The complete mtDNA genome sequence would
      contribute to studying phylogenetics in S. curriculus and gemplasm protection of
      aquatic animal in Pearl River.

PMID- 25865850
TI  - The role of the molecular chaperone heat shock protein A2 (HSPA2) in regulating
      human sperm-egg recognition.
AB  - One of the most common lesions present in the spermatozoa of human infertility
      patients is an idiopathic failure of sperm-egg recognition. Although this unique
      cellular interaction can now be readily by-passed by assisted reproductive
      strategies such as intracytoplasmic sperm injection (ICSI), recent large-scale
      epidemiological studies have encouraged the cautious use of this technology and
      highlighted the need for further research into the mechanisms responsible for
      defective sperm-egg recognition. Previous work in this field has established that
      the sperm domains responsible for oocyte interaction are formed during
      spermatogenesis prior to being dynamically modified during epididymal maturation
      and capacitation in female reproductive tract. While the factors responsible for
      the regulation of these sequential maturational events are undoubtedly complex,
      emerging research has identified the molecular chaperone, heat shock protein A2
      (HSPA2), as a key regulator of these events in human spermatozoa. HSPA2 is a
      testis-enriched member of the 70 kDa heat shock protein family that promotes the
      folding, transport, and assembly of protein complexes and has been positively
      correlated with in vitro fertilization (IVF) success. Furthermore, reduced
      expression of HSPA2 from the human sperm proteome leads to an impaired capacity
      for cumulus matrix dispersal, sperm-egg recognition and fertilization following
      both IVF and ICSI. In this review, we consider the evidence supporting the role
      of HSPA2 in sperm function and explore the potential mechanisms by which it is
      depleted in the spermatozoa of infertile patients. Such information offers novel
      insights into the molecular mechanisms governing sperm function. 

PMID- 25865852
TI  - Influence of educational attainments on long term glucose control and morbid
      events in patients with type 2 diabetes receiving integrated care from 15 China
      urban communities: The Beijing Community Diabetes Study 11.
AB  - AIM: To investigate the effects of educational attainment on glucose control and
      morbid events in patients with type 2 diabetes in Beijing communities. METHODS:
      In this prospective multi-center study, 2866 type 2 diabetes patients receiving
      integrated care from 15 Beijing urban communities were investigated. Educational
      attainment was categorized into three levels: low, medium, and high. After a 42
      month management, glucose control parameters and morbid events were analyzed.
      RESULTS: At baseline, the percentages of patients with good glucose control
      (HbA1c <= 7.0%) in the low, medium and high educational groups were 49.09%,
      54.82% and 62.59%, respectively (P<0.001). After the 42-month management, fasting
      plasma glucose and HbA1c values were the highest in the low educational group
      (7.51 +/- 2.05 mmol/l and 7.20 +/- 1.27%, respectively). Percentages of patients
      with good glucose control in the three groups were 49.6%, 55.83% and 67.23%,
      respectively, and the incidences of combined morbid events were 4.5%, 2.4% and
      1.5%, respectively. Cox regression analysis showed that educational level was
      related to the incidence of combined morbid events (medium level, HR=0.572; high
      level, HR=0.351; P<0.05). CONCLUSIONS: Educational level was associated with long
      term glucose control, and seemed to be related to the incidence of combined
      morbid events in people with type 2 diabetes.

PMID- 25865853
TI  - Adherence to national diabetes guidelines through monitoring quality indicators-
      A comparison of three types of care for the elderly with special emphasis on
      HbA1c.
AB  - AIM: To compare adherence to Swedish guidelines for diabetes care between elderly
      people living at home with or without home health care, and residents of nursing
      homes. METHODS: Medical records of 277 elderly people aged 80 and older, with
      known diabetes in a Swedish municipality, were monitored using quality indicators
      to evaluate processes and outcomes. RESULTS: Monitoring, in accordance to
      diabetes guidelines, of HbA1c, lipids, blood pressure and foot examinations was
      lower among residents of nursing homes (p < 0.001). The HbA1c value of <= 6.9%
      (52 mmol/mol) was achieved for 48% of those in nursing homes with medication, 35%
      and 39%, for those living at home with or without home health care, respectively.
      Insulin was used to a greater extent in nursing homes. Metformin was frequently
      used, even at reduced e-GFR. Systolic BP <= 140 mmHg was achieved by 71% vs 80%
      and 85% of those living at home, those with home health care and residents of
      nursing homes in the respective groups. CONCLUSIONS: Adherence to guidelines was
      deficient particularly in nursing homes. Clearer guidelines and interventions
      aimed at the improvement of quality in diabetes care in elderly people and
      sustainable coordination between health care providers is needed.

PMID- 25865855
TI  - Emerging drugs for the treatment of knee osteoarthritis.
AB  - INTRODUCTION: Osteoarthritis (OA) is the most prevailing form of joint disease,
      with symptoms affecting 10 - 12% of the adult population with a projection of a
      50% increase in prevalence in the next two decades. The disease characteristics
      are defined by articular cartilage damage, low-grade synovial inflammation and
      hypertrophic bone changes, leading to pain and functional deterioration. To date,
      available pain treatments are limited in their efficacy and have associated
      toxicities. No structural disease modification agents have been approved by
      regulatory agencies for this indication. AREAS COVERED: We reviewed drugs in
      Phase II - III for OA pain and joint structure modification. Different aspects of
      structure modification are divided into targets of inflammatory pathway,
      cartilage catabolism and anabolism, and subchondral bone remodeling. EXPERT
      OPINION: Further insight into the pathophysiology of the disease will allow for
      development of novel target classes focusing on the link between symptomatology
      and structural changes. Given the complexity of OA, one single therapy is
      unlikely to be universally and uniformly effective. Promising therapies are under
      development, but there are obstacles in the translation of treatment from
      preclinical models and trial designs need to be cognizant of the complex reasons
      for previous trial failures.

PMID- 25865856
TI  - Systemic inflammation as a therapeutic target in acute ischemic stroke.
AB  - Acute systemic inflammatory reaction superimposed on chronic low-grade
      inflammation accompanies acute ischemic stroke. Elevated blood levels of systemic
      inflammatory markers such as IL-6 or C-reactive protein are associated with an
      unfavorable functional outcome and increased mortality after stroke. Animal
      studies have demonstrated a causal relationship between systemic inflammation and
      ischemic brain damage. The mechanisms linking systemic inflammation with poor
      outcome include increased neutrophil infiltration of cerebral cortex, disruption
      of the blood-brain barrier, impaired tissue reperfusion, increased platelet
      activation and microvascular coagulation and complement-dependent brain injury.
      Non-selective (e.g., by statins) or selective (e.g., by inhibition of IL-6)
      attenuation of systemic inflammation, enhancement of systemic anti-inflammatory
      response (e.g., by infusion of IL-1 receptor antagonist), prevention of
      infections that exacerbate systemic inflammation or inhibition of neuronal
      pathways triggering inflammatory reaction are potential therapeutic targets in
      stroke patients. This review discusses the relationship between systemic
      inflammation, cerebral ischemia and prognosis in the context of therapeutic
      strategies. 

PMID- 25865857
TI  - Seafood traceability: current needs, available tools, and biotechnological
      challenges for origin certification.
AB  - Market globalization and recurring food safety alerts have resulted in a growing
      consumer awareness of the need for food traceability. This is particularly
      relevant for seafood due to its perishable nature and importance as a key protein
      source for the population of the world. Here, we provide an overview of the
      current needs for seafood origin traceability, along with the limitations and
      challenges for its implementation. We focus on geochemical, biochemical, and
      molecular tools and how they should be optimized to be implemented globally and
      to address our societal needs. We suggest that seafood traceability is key to
      enforcing food safety regulations and fisheries control, combat fraud, and
      fulfill present and future expectations of conscientious producers, consumers,
      and authorities. 

PMID- 25865859
TI  - Education and imaging. Gastroenterology: dysphagia aortica.

PMID- 25865858
TI  - Patterns of gestational weight gain related to fetal growth among women with
      overweight and obesity.
AB  - OBJECTIVE: Maternal obesity is associated with increased risk of large-for
      gestational-age (LGA) and small-for-gestational-age (SGA) births. Both are
      related to childhood obesity. This study considers that the patterns of
      gestational weight gain (GWG) may help to disentangle these competing risks.
      METHODS: Patterns of GWG were characterized among a cohort of women with
      overweight or obesity (n = 651). Polytomous logistic regression models were
      tested for associations between GWG patterns and birth weight outcomes: SGA
      (<10th) and LGA (>90th percentile). RESULTS: Rates of SGA were higher than those
      for LGA (14.9% vs. 7.8%). Four GWG patterns were identified: consistently high
      (29%), early adequate/late high (33%), consistently adequate (18%), and
      consistently low (20%). Risk of LGA was highest in women with consistently high
      GWG (adjusted odds ratio [OR] 4.62 [1.53, 13.96]), and risk was elevated, but
      with lower magnitude, among women with early adequate/late high gains (OR 3.07
      [1.01, 9.37]). High GWG before 20 weeks, regardless of later gain, was related to
      LGA. Low gain before 20 weeks accompanied by high gain later may be associated
      with reduced SGA risk (0.55 [0.29, 1.07]). CONCLUSIONS: The pattern of weight
      gain during pregnancy may be an important contributor to or marker of abnormal
      fetal growth among women with overweight or obesity.

PMID- 25865860
TI  - Education and imaging. Gastrointestinal: a rare case of oesophago-pericardial
      fistula in a 27 year-old man with achalasia.

PMID- 25865861
TI  - Education and imaging. Gastroenterology: video capsule endoscopy disclosure of
      unprecedented therapeutic effect of Eviendep on small bowel polyposis in Lynch
      syndrome.

PMID- 25865862
TI  - Education and imaging. Hepatology: Bilothorax after percutaneous transhepatic
      biliary drainage.

PMID- 25865863
TI  - Education and imaging. Hepatology: Chanarin-Dorfman syndrome, a rare cause of
      fatty liver and steatohepatitis.

PMID- 25865864
TI  - Fall rates in hospital rehabilitation units after individualised patient and
      staff education programmes: a pragmatic, stepped-wedge, cluster-randomised
      controlled trial.
AB  - BACKGROUND: Falls are the most frequent adverse events that are reported in
      hospitals. We examined the effectiveness of individualised falls-prevention
      education for patients, supported by training and feedback for staff, delivered
      as a ward-level programme. METHODS: Eight rehabilitation units in general
      hospitals in Australia participated in this stepped-wedge, cluster-randomised
      study, undertaken during a 50 week period. Units were randomly assigned to
      intervention or control groups by use of computer-generated, random allocation
      sequences. We included patients admitted to the unit during the study with a Mini
      Mental State Examination (MMSE) score of more than 23/30 to receive
      individualised education that was based on principles of changes in health
      behaviour from a trained health professional, in addition to usual care. We
      provided information about patients' goals, feedback about the ward environment,
      and perceived barriers to engagement in falls-prevention strategies to staff who
      were trained to support the uptake of strategies by patients. The coprimary
      outcome measures were patient rate of falls per 1000 patient-days and the
      proportion of patients who were fallers. All analyses were by intention to treat.
      This trial is registered with the Australian New Zealand Clinical Trials
      registry, number ACTRN12612000877886). FINDINGS: Between Jan 13, and Dec 27,
      2013, 3606 patients were admitted to the eight units (n=1983 control period;
      n=1623 intervention period). There were fewer falls (n=196, 7.80/1000 patient
      days vs n=380, 13.78/1000 patient-days, adjusted rate ratio 0.60 [robust 95% CI
      0.42-0.94], p=0.003), injurious falls (n=66, 2.63/1000 patient-days vs 131,
      4.75/1000 patient-days, 0.65 [robust 95% CI 0.42-0.88], p=0.006), and fallers
      (n=136 [8.38%] vs n=248 [12.51%] adjusted odds ratio 0.55 [robust 95% CI 0.38 to
      0.81], p=0.003) in the intervention compared with the control group. There was no
      significant difference in length of stay (intervention median 11 days [IQR 7-19],
      control 10 days [6-18]). INTERPRETATION: Individualised patient education
      programmes combined with training and feedback to staff added to usual care
      reduces the rates of falls and injurious falls in older patients in
      rehabilitation hospital-units. FUNDING: State Health Research Advisory Council,
      Department of Health, Government of Western Australia.

PMID- 25865865
TI  - Left ventricular non-compaction cardiomyopathy.
AB  - Left ventricular non-compaction, the most recently classified form of
      cardiomyopathy, is characterised by abnormal trabeculations in the left
      ventricle, most frequently at the apex. It can be associated with left
      ventricular dilation or hypertrophy, systolic or diastolic dysfunction, or both,
      or various forms of congenital heart disease. Affected individuals are at risk of
      left or right ventricular failure, or both. Heart failure symptoms can be induced
      by exercise or be persistent at rest, but many patients are asymptomatic.
      Patients on chronic treatment for compensated heart failure sometimes present
      acutely with decompensated heart failure. Other life-threatening risks of left
      ventricular non-compaction are ventricular arrhythmias or complete
      atrioventricular block, presenting clinically as syncope, and sudden death.
      Genetic inheritance arises in at least 30-50% of patients, and several genes that
      cause left ventricular non-compaction have been identified. These genes seem
      generally to encode sarcomeric (contractile apparatus) or cytoskeletal proteins,
      although, in the case of left ventricular non-compaction with congenital heart
      disease, disturbance of the NOTCH signalling pathway seems part of a final common
      pathway for this form of the disease. Disrupted mitochondrial function and
      metabolic abnormalities have a causal role too. Treatments focus on improvement
      of cardiac efficiency and reduction of mechanical stress in patients with
      systolic dysfunction. Further, treatment of arrhythmia and implantation of an
      automatic implantable cardioverter-defibrillator for prevention of sudden death
      are mainstays of therapy when deemed necessary and appropriate. Patients with
      left ventricular non-compaction and congenital heart disease often need surgical
      or catheter-based interventions. Despite progress in diagnosis and treatment in
      the past 10 years, understanding of the disorder and outcomes need to be
      improved. 

PMID- 25865867
TI  - 10th international scientific conference of the international occupational
      hygiene association, london april 25-30, 2015: program abstracts.

PMID- 25865866
TI  - The case for stepped-wedge studies: a trial of falls prevention.

PMID- 25865869
TI  - Distribution of vitamin C is tissue specific with early saturation of the brain
      and adrenal glands following differential oral dose regimens in guinea pigs.
AB  - Vitamin C (VitC) deficiency is surprisingly common in humans even in developed
      parts of the world. The micronutrient has several established functions in the
      brain; however, the consequences of its deficiency are not well characterised. To
      elucidate the effects of VitC deficiency on the brain, increased knowledge about
      the distribution of VitC to the brain and within different brain regions after
      varying dietary concentrations is needed. In the present study, guinea pigs (like
      humans lacking the ability to synthesise VitC) were randomly divided into six
      groups (n 10) that received different concentrations of VitC ranging from 100 to
      1500 mg/kg feed for 8 weeks, after which VitC concentrations in biological fluids
      and tissues were measured using HPLC. The distribution of VitC was found to be
      dynamic and dependent on dietary availability. Brain saturation was region
      specific, occurred at low dietary doses, and the dose-concentration relationship
      could be approximated with a three-parameter Hill equation. The correlation
      between plasma and brain concentrations of VitC was moderate compared with other
      organs, and during non-scorbutic VitC deficiency, the brain was able to maintain
      concentrations from about one-quarter to half of sufficient levels depending on
      the region, whereas concentrations in other tissues decreased to one-sixth or
      less. The adrenal glands have similar characteristics to the brain. The observed
      distribution kinetics with a low dietary dose needed for saturation and
      exceptional retention ability suggest that the brain and adrenal glands are high
      priority tissues with regard to the distribution of VitC.

PMID- 25865870
TI  - Electrical control of the exchange spring in antiferromagnetic metals.
AB  - Electrical control of the exchange spring in antiferromagnetic metals is obtained
      in [Co/Pt]/IrMn Hall devices by using an ionic liquid, where the exchange spring
      could transfer the "force" and enable a deeper modulation depth in the IrMn. This
      work provides a new approach toward electrical modulation of the spin structures
      in metallic antiferromagnets, which should be significant in advancing the
      development of low-power-consumption antiferromagnet (AFM) spintronics. 

PMID- 25865871
TI  - Concentration dependence of yield stress and dynamic moduli of kaolinite
      suspensions.
AB  - The concentration dependence of yield stress and dynamic moduli of kaolinite
      suspensions is studied. Complex electrostatic interactions between kaolinite
      platelets promote a more liquid-like behavior, with clay particles changing from
      attractive interactions to a face-face repulsive interaction as the mass fraction
      of clay particles increases. A yield stress model is developed based on the
      repulsive interaction between disk-shaped particles, which yields a good
      prediction of experimental observations when repulsive face-face interaction is
      dominant. The critical concentration when attractive interaction changes
      completely to face-face repulsive interaction is estimated from the theory. Four
      regions are identified in the variation of yield stress as a function of the
      concentration. 

PMID- 25865872
TI  - Paternal age and telomere length in twins: the germ stem cell selection paradigm.
AB  - Telomere length, a highly heritable trait, is longer in offspring of older
      fathers. This perplexing feature has been attributed to the longer telomeres in
      sperm of older men and it might be an 'epigenetic' mechanism through which
      paternal age plays a role in telomere length regulation in humans. Based on two
      independent (discovery and replication) twin studies, comprising 889 twin pairs,
      we show an increase in the resemblance of leukocyte telomere length between
      dizygotic twins of older fathers, which is not seen in monozygotic twins. This
      phenomenon might result from a paternal age-dependent germ stem cell selection
      process, whereby the selected stem cells have longer telomeres, are more
      homogenous with respect to telomere length, and share resistance to aging. 

PMID- 25865873
TI  - Bone as a Structural Material.
AB  - As one of the most important natural materials, cortical bone is a composite
      material comprising assemblies of tropocollagen molecules and nanoscale
      hydroxyapatite mineral crystals, forming an extremely tough, yet lightweight,
      adaptive and multi-functional material. Bone has evolved to provide structural
      support to organisms, and therefore its mechanical properties are vital
      physiologically. Like many mineralized tissues, bone can resist deformation and
      fracture from the nature of its hierarchical structure, which spans molecular to
      macroscopic length-scales. In fact, bone derives its fracture resistance with a
      multitude of deformation and toughening mechanisms that are active at most of
      these dimensions. It is shown that bone's strength and ductility originate
      primarily at the scale of the nano to submicrometer structure of its mineralized
      collagen fibrils and fibers, whereas bone toughness is additionally generated at
      much larger, micro- to near-millimeter, scales from crack-tip shielding
      associated with interactions between the crack path and the microstructure. It is
      further shown how the effectiveness with which bone's structural features can
      resist fracture at small to large length-scales can become degraded by biological
      factors such as aging and disease, which affect such features as the collagen
      cross-linking environment, the homogeneity of mineralization, and the density of
      the osteonal structures. 

PMID- 25865875
TI  - A consensus approach to improving patient adherence and persistence with topical
      treatment for actinic keratosis.
AB  - BACKGROUND: Topical therapy is important in the treatment of actinic keratosis,
      but guidance for improving adherence/persistence during topical therapy is still
      lacking. OBJECTIVES: To utilize expert consensus to generate a list of
      recommendations to improve real-world efficacy when prescribing topical therapy
      for actinic keratosis. METHODS: An expert panel of eight dermatologists was
      convened to generate recommendations based on facilitated discussion and
      consensus generation using a modified Delphi session. The recommendations were
      ratified with the expert panel. RESULTS: Facilitated discussion generated 31
      issues within five themes, which were prioritized using expert voting. Consensus
      was achieved on the importance of short and simple treatment regimens for
      maximizing patient compliance, physician awareness of the progression of actinic
      keratosis to squamous cell carcinoma, provision of appropriate patient
      information, and the use of effective communication strategies to educate
      physicians about actinic keratosis. Based on these key findings, eight
      recommendations were generated. CONCLUSIONS: The recommendations will assist
      physicians when prescribing topical actinic keratosis therapy. Further research
      should focus on the types of patient outcomes that are influenced by the
      characteristics of topical field therapy.

PMID- 25865874
TI  - A fungal protease allergen provokes airway hyper-responsiveness in asthma.
AB  - Asthma, a common disorder that affects >250 million people worldwide, is defined
      by exaggerated bronchoconstriction to inflammatory mediators including
      acetylcholine (ACh), bradykinin and histamine-also termed airway hyper
      responsiveness. Nearly 10% of people with asthma have severe, treatment-resistant
      disease, which is frequently associated with immunoglobulin-E sensitization to
      ubiquitous fungi, typically Aspergillus fumigatus (Af). Here we show that a major
      Af allergen, Asp f13, which is a serine protease, alkaline protease 1 (Alp 1),
      promotes airway hyper-responsiveness by infiltrating the bronchial submucosa and
      disrupting airway smooth muscle (ASM) cell-extracellular matrix (ECM)
      interactions. Alp 1-mediated ECM degradation evokes pathophysiological RhoA
      dependent Ca(2+) sensitivity and bronchoconstriction. These findings support a
      pathogenic mechanism in asthma and other lung diseases associated with epithelial
      barrier impairment, whereby ASM cells respond directly to inhaled environmental
      allergens to generate airway hyper-responsiveness. 

PMID- 25865876
TI  - Clozapine-induced myocarditis: prescribe safely but do prescribe.

PMID- 25865877
TI  - The Order of Australia: recognition for national role models.

PMID- 25865878
TI  - Mindfulness based interventions and Cognitive Behavioural Therapy are shown to
      have similar effect in the short-term treatment of anxiety, depression and
      stress.

PMID- 25865879
TI  - A meta-analysis of Mindfulness Based Interventions (MBIs) show that MBIs are
      effective in reducing acute symptoms of depression but not anxiety.

PMID- 25865881
TI  - IKCa channels are a critical determinant of the slow AHP in CA1 pyramidal
      neurons.
AB  - Control over the frequency and pattern of neuronal spike discharge depends on
      Ca2+-gated K+ channels that reduce cell excitability by hyperpolarizing the
      membrane potential. The Ca2+-dependent slow afterhyperpolarization (sAHP) is one
      of the most prominent inhibitory responses in the brain, with sAHP amplitude
      linked to a host of circuit and behavioral functions, yet the channel that
      underlies the sAHP has defied identification for decades. Here, we show that
      intermediate-conductance Ca2+-dependent K+ (IKCa) channels underlie the sAHP
      generated by trains of synaptic input or postsynaptic stimuli in CA1 hippocampal
      pyramidal cells. These findings are significant in providing a molecular identity
      for the sAHP of central neurons that will identify pharmacological tools capable
      of potentially modifying the several behavioral or disease states associated with
      the sAHP.

PMID- 25865882
TI  - Specific downregulation of hippocampal ATF4 reveals a necessary role in synaptic
      plasticity and memory.
AB  - Prior studies suggested that the transcription factor ATF4 negatively regulates
      synaptic plastic and memory. By contrast, we provide evidence from direct in
      vitro and in vivo knockdown of ATF4 in rodent hippocampal neurons and from ATF4
      null mice that implicate ATF4 as essential for normal synaptic plasticity and
      memory. In particular, hippocampal ATF4 downregulation produces deficits in long
      term spatial memory and behavioral flexibility without affecting associative
      memory or anxiety-like behavior. ATF4 knockdown or loss also causes profound
      impairment of both long-term potentiation (LTP) and long-term depression (LTD) as
      well as decreased glutamatergic function. We conclude that ATF4 is a key
      regulator of the physiological state necessary for neuronal plasticity and
      memory.

PMID- 25865883
TI  - RIOK3-mediated phosphorylation of MDA5 interferes with its assembly and
      attenuates the innate immune response.
AB  - MDA5 is a cytoplasmic viral double-stranded RNA (dsRNA) sensor and triggers type
      I interferon (IFN) production. MDA5 assembles along viral dsRNA, leading to the
      formation of an MDA5 filament required for activating the MAVS adaptor. A recent
      study has revealed that PP1alpha and PP1gamma phosphatases are responsible for
      dephosphorylating MDA5 and are essential for its activation. Here, we identified
      RIO kinase 3 (RIOK3) as a protein kinase that phosphorylates the MDA5 C-terminal
      region. RIOK3 knockout strongly enhanced type I IFN and IFN-inducible gene
      expression following measles virus infection. Conversely, the ectopic expression
      of RIOK3 or a phosphomimetic MDA5-S828D mutation attenuated MDA5-mediated
      signaling. Moreover, RIOK3-mediated MDA5 phosphorylation impaired MDA5 multimer
      formation, indicating that MDA5 C-terminal phosphorylation interferes with MDA5
      filament formation and suppresses its signaling. Our data revealed a regulatory
      mechanism underlying the activation of the cytoplasmic viral RNA sensor MDA5 in
      both uninfected and virus-infected cells.

PMID- 25865884
TI  - Cytoplasmic dynein is required for the spatial organization of protein aggregates
      in filamentous fungi.
AB  - Eukaryotes have evolved multiple strategies for maintaining cellular protein
      homeostasis. One such mechanism involves neutralization of deleterious protein
      aggregates via their defined spatial segregation. Here, using the molecular
      disaggregase Hsp104 as a marker for protein aggregation, we describe the spatial
      and temporal dynamics of protein aggregates in the filamentous fungus Aspergillus
      nidulans. Filamentous fungi, such as A. nidulans, are a diverse group of species
      of major health and economic importance and also serve as model systems for
      studying highly polarized eukaryotic cells. We find that microtubules promote the
      formation of Hsp104-positive aggregates, which coalesce into discrete subcellular
      structures in a process dependent on the microtubule-based motor cytoplasmic
      dynein. Finally, we find that impaired clearance of these inclusions negatively
      impacts retrograde trafficking of endosomes, a conventional dynein cargo,
      indicating that microtubule-based transport can be overwhelmed by chronic
      cellular stress.

PMID- 25865885
TI  - Oscillatory activity in developing prefrontal networks results from theta-gamma
      modulated synaptic inputs.
AB  - The hippocampus-driven entrainment of neonatal prefrontal circuits in theta-gamma
      oscillations contributes to the maturation of cognitive abilities, yet the
      underlying synaptic mechanisms are still unknown. Here we combine patch-clamp
      recordings from morphologically and neurochemically characterized layer V
      pyramidal neurons and interneurons in vivo, with extracellular recordings from
      the prelimbic cortex (PL) of awake and lightly anesthetized neonatal rats, to
      elucidate the synaptic framework of early network oscillations. We demonstrate
      that all neurons spontaneously fire bursts of action potentials. They receive
      barrages of fast and slow glutamatergic as well as GABAergic synaptic inputs.
      Oscillatory theta activity results from long-range coupling of pyramidal neurons,
      presumably within prelimbic-hippocampal circuits, and from local interactions
      between interneurons. In contrast, beta-low gamma activity requires external
      glutamatergic drive on prelimbic interneurons. High-frequency oscillations in
      layer V are independent of interactions at chemical synapses. Thus, specific
      theta-gamma-modulated synaptic interactions represent the substrate of network
      oscillations in the developing PL. 

PMID- 25865886
TI  - Ribosomal S6K1 in POMC and AgRP Neurons Regulates Glucose Homeostasis but Not
      Feeding Behavior in Mice.
AB  - Hypothalamic ribosomal S6K1 has been suggested as a point of convergence for
      hormonal and nutrient signals in the regulation of feeding behavior, bodyweight,
      and glucose metabolism. However, the long-term effects of manipulating
      hypothalamic S6K1 signaling on energy homeostasis and the cellular mechanisms
      underlying these roles are unclear. We therefore inactivated S6K1 in pro
      opiomelanocortin (POMC) and agouti-related protein (AgRP) neurons, key regulators
      of energy homeostasis, but in contrast to the current view, we found no evidence
      that S6K1 regulates food intake and bodyweight. In contrast, S6K1 signaling in
      POMC neurons regulated hepatic glucose production and peripheral lipid metabolism
      and modulated neuronal excitability. S6K1 signaling in AgRP neurons regulated
      skeletal muscle insulin sensitivity and was required for glucose sensing by these
      neurons. Our findings suggest that S6K1 signaling is not a general integrator of
      energy homeostasis in the mediobasal hypothalamus but has distinct roles in the
      regulation of glucose homeostasis by POMC and AgRP neurons. 

PMID- 25865887
TI  - Identification of a Non-Gatekeeper Hot Spot for Drug-Resistant Mutations in mTOR
      Kinase.
AB  - Protein kinases are therapeutic targets for human cancer. However, "gatekeeper"
      mutations in tyrosine kinases cause acquired clinical resistance, limiting long
      term treatment benefits. mTOR is a key cancer driver and drug target. Numerous
      small-molecule mTOR kinase inhibitors have been developed, with some already in
      human clinical trials. Given our clinical experience with targeted therapeutics,
      acquired drug resistance in mTOR is thought likely, but not yet documented.
      Herein, we describe identification of a hot spot (L2185) for drug-resistant
      mutations, which is distinct from the gatekeeper site, and a chemical scaffold
      refractory to drug-resistant mutations. We also provide new insights into mTOR
      kinase structure and function. The hot spot mutations are potentially useful as
      surrogate biomarkers for acquired drug resistance in ongoing clinical trials and
      future treatments and for the design of the next generation of mTOR-targeted
      drugs. Our study provides a foundation for further research into mTOR kinase
      function and targeting. 

PMID- 25865888
TI  - Inhibition of Lapatinib-Induced Kinome Reprogramming in ERBB2-Positive Breast
      Cancer by Targeting BET Family Bromodomains.
AB  - Therapeutics that target ERBB2, such as lapatinib, often provide initial clinical
      benefit, but resistance frequently develops. Adaptive responses leading to
      lapatinib resistance involve reprogramming of the kinome through reactivation of
      ERBB2/ERBB3 signaling and transcriptional upregulation and activation of multiple
      tyrosine kinases. The heterogeneity of induced kinases prevents their targeting
      by a single kinase inhibitor, underscoring the challenge of predicting effective
      kinase inhibitor combination therapies. We hypothesized that, to make the tumor
      response to single kinase inhibitors durable, the adaptive kinome response itself
      must be inhibited. Genetic and chemical inhibition of BET bromodomain chromatin
      readers suppresses transcription of many lapatinib-induced kinases involved in
      resistance, including ERBB3, IGF1R, DDR1, MET, and FGFRs, preventing downstream
      SRC/FAK signaling and AKT reactivation. Combining inhibitors of kinases and
      chromatin readers prevents kinome adaptation by blocking transcription,
      generating a durable response to lapatinib, and overcoming the dilemma of
      heterogeneity in the adaptive response. 

PMID- 25865890
TI  - Crystal Structure and Activity of the Endoribonuclease Domain of the piRNA
      Pathway Factor Maelstrom.
AB  - PIWI-interacting RNAs (piRNAs) protect the genome from transposons in animal
      gonads. Maelstrom (Mael) is an evolutionarily conserved protein, composed of a
      high-mobility group (HMG) domain and a MAEL domain, and is essential for piRNA
      mediated transcriptional transposon silencing in various species, such as
      Drosophila and mice. However, its structure and biochemical function have
      remained elusive. Here, we report the crystal structure of the MAEL domain from
      Drosophila melanogaster Mael, at 1.6 A resolution. The structure reveals that the
      MAEL domain has an RNase H-like fold but lacks canonical catalytic residues
      conserved among RNase H-like superfamily nucleases. Our biochemical analyses
      reveal that the MAEL domain exhibits single-stranded RNA (ssRNA)-specific
      endonuclease activity. Our cell-based analyses further indicate that ssRNA
      cleavage activity appears dispensable for piRNA-mediated transcriptional
      transposon silencing in Drosophila. Our findings provide clues toward
      understanding the multiple roles of Mael in the piRNA pathway. 

PMID- 25865889
TI  - Behavioral disturbances in estrogen-related receptor alpha-null mice.
AB  - Eating disorders, such as anorexia nervosa and bulimia nervosa, are common and
      severe mental illnesses of unknown etiology. Recently, we identified a rare
      missense mutation in the transcription factor estrogen-related receptor alpha
      (ESRRA) that is associated with the development of eating disorders. However,
      little is known about ESRRA function in the brain. Here, we report that Esrra is
      expressed in the mouse brain and demonstrate that Esrra levels are regulated by
      energy reserves. Esrra-null female mice display a reduced operant response to a
      high-fat diet, compulsivity/behavioral rigidity, and social deficits. Selective
      Esrra knockdown in the prefrontal and orbitofrontal cortices of adult female mice
      recapitulates reduced operant response and increased compulsivity, respectively.
      These results indicate that Esrra deficiency in the mouse brain impairs
      behavioral responses in multiple functional domains. 

PMID- 25865891
TI  - Cellular Levels of Signaling Factors Are Sensed by beta-actin Alleles to Modulate
      Transcriptional Pulse Intensity.
AB  - The transcriptional response of beta-actin to extra-cellular stimuli is a
      paradigm for transcription factor complex assembly and regulation. Serum
      induction leads to a precisely timed pulse of beta-actin transcription in the
      cell population. Actin protein is proposed to be involved in this response, but
      it is not known whether cellular actin levels affect nuclear beta-actin
      transcription. We perturbed the levels of key signaling factors and examined the
      effect on the induced transcriptional pulse by following endogenous beta-actin
      alleles in single living cells. Lowering serum response factor (SRF) protein
      levels leads to loss of pulse integrity, whereas reducing actin protein levels
      reveals positive feedback regulation, resulting in elevated gene activation and a
      prolonged transcriptional response. Thus, transcriptional pulse fidelity requires
      regulated amounts of signaling proteins, and perturbations in factor levels
      eliminate the physiological response, resulting in either tuning down or
      exaggeration of the transcriptional pulse. 

PMID- 25865892
TI  - Genome-derived cytosolic DNA mediates type I interferon-dependent rejection of B
      cell lymphoma cells.
AB  - The DNA damage response (DDR) induces the expression of type I interferons
      (IFNs), but the underlying mechanisms are poorly understood. Here, we show the
      presence of cytosolic DNA in different mouse and human tumor cells. Treatment of
      cells with genotoxic agents increased the levels of cytosolic DNA in a DDR
      dependent manner. Cloning of cytosolic DNA molecules from mouse lymphoma cells
      suggests that cytosolic DNA is derived from unique genomic loci and has the
      potential to form non-B DNA structures, including R-loops. Overexpression of
      Rnaseh1, which resolves R-loops, reduced the levels of cytosolic DNA, type I Ifn
      transcripts, and type I IFN-dependent rejection of lymphoma cells. Live-cell
      imaging showed a dynamic contact of cytosolic DNA with mitochondria, an important
      organelle for innate immune recognition of cytosolic nucleotides. In summary, we
      found that cytosolic DNA is present in many tumor cells and contributes to the
      immunogenicity of tumor cells. 

PMID- 25865893
TI  - Entosis allows timely elimination of the luminal epithelial barrier for embryo
      implantation.
AB  - During implantation, uterine luminal epithelial (LE) cells first interact with
      the blastocyst trophectoderm. Within 30 hr after the initiation of attachment, LE
      cells surrounding the blastocyst in the implantation chamber (crypt) disappear,
      allowing trophoblast cells to make direct physical contact with the underneath
      stroma for successful implantation. The mechanism for the extraction of LE cells
      was thought to be mediated by apoptosis. Here, we show that LE cells in direct
      contact with the blastocyst are endocytosed by trophoblast cells by adopting the
      nonapoptotic cell-in-cell invasion process (entosis) in the absence of caspase 3
      activation. Our in vivo observations were reinforced by the results of co-culture
      experiments with primary uterine epithelial cells with trophoblast stem cells or
      blastocysts showing internalization of epithelial cells by trophoblasts. We have
      identified entosis as a mechanism to remove LE cells by trophoblast cells in
      implantation, conferring a role for entosis in an important physiological
      process. 

PMID- 25865894
TI  - An Intrinsically Disordered Peptide from Ebola Virus VP35 Controls Viral RNA
      Synthesis by Modulating Nucleoprotein-RNA Interactions.
AB  - During viral RNA synthesis, Ebola virus (EBOV) nucleoprotein (NP) alternates
      between an RNA-template-bound form and a template-free form to provide the viral
      polymerase access to the RNA template. In addition, newly synthesized NP must be
      prevented from indiscriminately binding to noncognate RNAs. Here, we investigate
      the molecular bases for these critical processes. We identify an intrinsically
      disordered peptide derived from EBOV VP35 (NPBP, residues 20-48) that binds NP
      with high affinity and specificity, inhibits NP oligomerization, and releases RNA
      from NP-RNA complexes in vitro. The structure of the NPBP/DeltaNPNTD complex,
      solved to 3.7 A resolution, reveals how NPBP peptide occludes a large surface
      area that is important for NP-NP and NP-RNA interactions and for viral RNA
      synthesis. Together, our results identify a highly conserved viral interface that
      is important for EBOV replication and can be targeted for therapeutic
      development. 

PMID- 25865895
TI  - Two functionally distinct sources of actin monomers supply the leading edge of
      lamellipodia.
AB  - Lamellipodia, the sheet-like protrusions of motile cells, consist of networks of
      actin filaments (F-actin) regulated by the ordered assembly from and disassembly
      into actin monomers (G-actin). Traditionally, G-actin is thought to exist as a
      homogeneous pool. Here, we show that there are two functionally and molecularly
      distinct sources of G-actin that supply lamellipodial actin networks. G-actin
      originating from the cytosolic pool requires the monomer-binding protein thymosin
      beta4 (Tbeta4) for optimal leading-edge localization, is targeted to formins, and
      is responsible for creating an elevated G/F-actin ratio that promotes membrane
      protrusion. The second source of G-actin comes from recycled lamellipodia F
      actin. Recycling occurs independently of Tbeta4 and appears to regulate
      lamellipodia homeostasis. Tbeta4-bound G-actin specifically localizes to the
      leading edge because it does not interact with Arp2/3-mediated polymerization
      sites found throughout the lamellipodia. These findings demonstrate that actin
      networks can be constructed from multiple sources of monomers with discrete
      spatiotemporal functions. 

PMID- 25865896
TI  - ATRX Plays a Key Role in Maintaining Silencing at Interstitial Heterochromatic
      Loci and Imprinted Genes.
AB  - Histone H3.3 is a replication-independent histone variant, which replaces
      histones that are turned over throughout the entire cell cycle. H3.3 deposition
      at euchromatin is dependent on HIRA, whereas ATRX/Daxx deposits H3.3 at
      pericentric heterochromatin and telomeres. The role of H3.3 at heterochromatic
      regions is unknown, but mutations in the ATRX/Daxx/H3.3 pathway are linked to
      aberrant telomere lengthening in certain cancers. In this study, we show that
      ATRX-dependent deposition of H3.3 is not limited to pericentric heterochromatin
      and telomeres but also occurs at heterochromatic sites throughout the genome.
      Notably, ATRX/H3.3 specifically localizes to silenced imprinted alleles in mouse
      ESCs. ATRX KO cells failed to deposit H3.3 at these sites, leading to loss of the
      H3K9me3 heterochromatin modification, loss of repression, and aberrant allelic
      expression. We propose a model whereby ATRX-dependent deposition of H3.3 into
      heterochromatin is normally required to maintain the memory of silencing at
      imprinted loci. 

PMID- 25865897
TI  - The ontogeny of the chin: an analysis of allometric and biomechanical scaling.
AB  - The presence of a prominent chin in modern humans has been viewed by some
      researchers as an architectural adaptation to buttress the anterior corpus from
      bending stresses during mastication. In contrast, ontogenetic studies of
      mandibular symphyseal form suggest that a prominent chin results from the complex
      spatial interaction between the symphysis and surrounding soft tissue and
      skeletal anatomy during development. While variation in chin prominence is
      clearly influenced by differential growth and spatial constraints, it is unclear
      to what degree these developmental dynamics influence the mechanical properties
      of the symphysis. That is, do ontogenetic changes in symphyseal shape result in
      increased symphyseal bending resistance? We examined ontogenetic changes in the
      mechanical properties and shape of the symphysis using subjects from a
      longitudinal cephalometric growth study with ages ranging from 3 to 20+ years. We
      first examined whether ontogenetic changes in symphyseal shape were correlated
      with symphyseal vertical bending and wishboning resistance using multivariate
      regression. Secondly, we examined ontogenetic scaling of bending resistance
      relative to bending moment arm lengths. An ontogenetic increase in chin
      prominence was associated with decreased vertical bending resistance, while
      wishboning resistance was uncorrelated with ontogenetic development of the chin.
      Relative to bending moment arm lengths, vertical bending resistance scaled with
      significant negative allometry whereas wishboning resistance scaled
      isometrically. These results suggest a complex interaction between symphyseal
      ontogeny and bending resistance, and indicate that ontogenetic increases in chin
      projection do not provide greater bending resistance to the mandibular symphysis.

PMID- 25865898
TI  - Diplopia: a diagnostic challenge with common and rare etiologies.
AB  - BACKGROUND: Diplopia is a symptom with very different etiologies. It may be
      caused by pathology in the eye, orbit, extraocular muscles, neuromuscular
      junction, or in the central nervous system. CASE REPORT: Three clinical cases of
      hospitalization due to isolated diplopia are presented here, illustrating
      different etiologies. CONCLUSIONS: The present article aims to address the
      differential diagnosis of this clinical condition and to warn of less frequent
      causes of diplopia, such as adverse effects of commonly used drugs.

PMID- 25865899
TI  - Challenges of intra-institutional transfer of care from paediatric to adult
      congenital cardiology: the need for retention as well as transition.
AB  - BACKGROUND: Transferring patients with CHD from paediatric to adult care has been
      challenging, especially across institutions. Within a single institution, some
      issues such as provider interaction, information exchange, or administrative
      directives should not play a significant role, and should favour successful
      transfer. OBJECTIVE: We studied patients who were eligible for transfer to the
      adult congenital heart disease service within our institution in order to
      identify factors associated with successful transfer to adult care providers
      versus failure to transfer. METHODS: Patients above18 years of age with CHD who
      were seen by paediatric cardiologists before January, 2008 were identified
      through a patient-care database. Records were reviewed to determine follow-up
      between 2008 and 2011 and to determine whether the patient was seen in the adult
      congenital cardiology clinic, paediatric cardiology clinic, or had no follow-up,
      and statistical comparisons were made between groups. RESULTS: After reviewing
      916 records, 229 patients were considered eligible for transition to adult
      congenital cardiology. Of these, 77 (34%) were transferred successfully to adult
      congenital cardiology, 47 (21%) continued to be seen by paediatric cardiologists,
      and 105 (46%) were lost to follow-up. Those who transferred successfully differed
      with regard to complexity of diagnosis, insurance, and whether a formal referral
      was made by a paediatric care provider. Only a small fraction of the patients who
      were lost to follow-up could be contacted. CONCLUSION: Within a single
      institution, with shared information systems, administrations, and care
      providers, successful transfer from paediatric to adult congenital cardiology was
      still poor. Efforts for successful retention are just as vital as those for
      transfer.

PMID- 25865900
TI  - A Meta-Analysis of Renal Function After Adult Cardiac Surgery With Pulsatile
      Perfusion.
AB  - The aim of this meta-analysis was to determine whether pulsatile perfusion during
      cardiac surgery has a lesser effect on renal dysfunction than nonpulsatile
      perfusion after cardiac surgery in randomized controlled trials. MEDLINE, EMBASE,
      and the Cochrane Central Register of Controlled Trials were used to identify
      available articles published before April 25, 2014. Meta-analysis was conducted
      to determine the effects of pulsatile perfusion on postoperative renal functions,
      as determined by creatinine clearance (CrCl), serum creatinine (Cr), urinary
      neutrophil gelatinase-associated lipocalin (NGAL), and the incidences of acute
      renal insufficiency (ARI) and acute renal failure (ARF). Nine studies involving
      674 patients that received pulsatile perfusion and 698 patients that received
      nonpulsatile perfusion during cardiopulmonary bypass (CPB) were considered in the
      meta-analysis. Stratified analysis was performed according to effective
      pulsatility or unclear pulsatility of the pulsatile perfusion method in the
      presence of heterogeneity. NGAL levels were not significantly different between
      the pulsatile and nonpulsatile groups. However, patients in the pulsatile group
      had a significantly higher CrCl and lower Cr levels when the analysis was
      restricted to studies on effective pulsatile flow (P < 0.00001, respectively).
      The incidence of ARI was significantly lower in the pulsatile group (P <
      0.00001), but incidences of ARF were similar. In conclusion, the meta-analysis
      suggests that the use of pulsatile flow during CPB results in better
      postoperative renal function. 

PMID- 25865906
TI  - Adaptive expression of uncoupling protein 1 in the carp liver and kidney in
      response to changes in ambient temperature.
AB  - The expression of uncoupling protein (UCP1) is up-regulated in mammalian brown
      adipocytes during cold exposure. However, a previous study revealed that UCP1 was
      highly expressed in the liver of common carps, and that the hepatic expression of
      UCP1 was down-regulated during cold exposure. The present study examined the
      effects of temperature on the recovery of UCP1 expression levels and the
      expression of genes involved in UCP1 transcription in the livers and kidneys of
      common carps. The hepatic and renal expressions of UCP1 were decreased by
      acclimation from 22  degrees C to 8  degrees C, and a subsequent increase in the
      water temperature from 8  degrees C to 28  degrees C recovered the renal, but not
      hepatic expression of UCP1. Changes in the expression of peroxisome proliferator
      activator receptor (PPAR) gamma, retinoid X receptor (RXR) alpha and PPARgamma co
      activator (PGC)-1alpha, genes that are involved in the expression of UCP1 in
      mammals, with ambient temperature indicated that the expressions of PPARgamma and
      RXRalpha, but not expression of PGC-1alpha was decreased in response to cold
      exposure; the hepatic and renal expressions of PPARgamma and RXRalpha recovered
      to basal levels with the cessation of cold exposure, although this was not
      complete for hepatic expression of PPARgamma. The results of the present study
      indicate that a unique regulatory mechanism is responsible for the hepatic and
      renal expressions of carp UCP1 during cold exposure and subsequent reacclimation,
      and is distinct from that in murine brown adipocytes.

PMID- 25865907
TI  - Latent class analysis of substance use among men who have sex with men in
      Malaysia: Findings from the Asian Internet MSM Sex Survey.
AB  - BACKGROUND: High prevalence of substance use among men who have sex with men
      (MSM) may drive the HIV epidemic in Malaysia but patterns of substance use among
      Malaysian MSM have not been examined. Our study investigated specific Malaysian
      MSM risk groups to determine the association between their substance use and
      sexual risk behaviors. METHODS: Data from Malaysian respondents (n=1235) in a
      large, multinational online survey of Asian MSM in 2010 were used to identify
      latent classes of substance use. Subsequent covariates were included in a joint
      model to predict class membership. RESULTS: The 3-class model was identified as
      the best fitting model, which included: (1) 'negligible substance use' for those
      reporting none or using any substance sparingly; (2) 'soft substance use' for
      those using poppers, ecstasy and drinking before sex; and (3) 'amphetamine-type
      stimulant (ATS) use' for those using stimulants (methamphetamine, ecstasy),
      erectile dysfunction drugs and recreational drug use before sex. Men in the 'ATS
      use' category were significantly less likely to not know their HIV status (AOR:
      0.30, 95%CI: 0.14,0.66), more likely to have had more than 6 male sex partners
      (AOR: 4.83, 95% CI: 1.92-12.2), to have group sex (AOR:4.07, 95% CI: 2.31-7.15),
      to report inconsistent condom use (AOR:2.01, 95% CI: 1.12-3.60), to be HIV
      infected (AOR:3.92, 95% CI: 1.63-8.42) and to have had any sexually transmitted
      infections (AOR:3.92, 95% CI:1.70, 9.08), compared to men in the 'negligible
      substance use' category. CONCLUSIONS: Our study identified subgroups of Malaysian
      MSM with distinct substance use patterns and HIV-related risk profiles, which
      provides implication for targeting HIV prevention in this subpopulation.

PMID- 25865908
TI  - Reduced frontal cortical thickness and increased caudate volume within fronto
      striatal circuits in young adult smokers.
AB  - BACKGROUND: Smoking during early adulthood results in neurophysiological and
      brain structural changes that may promote nicotine dependence later in life.
      Previous studies have revealed the important roles of fronto-striatal circuits in
      the pathology of nicotine dependence; however, few studies have focused on both
      cortical thickness and subcortical striatal volume differences between young
      adult smokers and nonsmokers. METHODS: Twenty-seven young male adult smokers and
      22 age-, education- and gender-matched nonsmokers were recruited in the present
      study. The cortical thickness and striatal volume differences of young adult
      smokers and age-matched nonsmokers were investigated in the present study and
      then correlated with pack-years and Fagerstrom Test for Nicotine Dependence
      (FTND). RESULTS: The following results were obtained: (1) young adult smokers
      showed significant cortical thinning in the frontal cortex (left caudal anterior
      cingulate cortex (ACC), right lateral orbitofrontal cortex (OFC)), left insula,
      left middle temporal gyrus, right inferior parietal lobule, and right
      parahippocampus; (2) in regards to subcortical striatal volume, the volume of the
      right caudate was larger in young adult smokers than nonsmokers; and (3) the
      cortical thickness of the right dorsolateral prefrontal cortex (DLPFC) and OFC
      were associated with nicotine dependence severity (FTND) and cumulative amount of
      nicotine intake (pack-years) in smokers, respectively. CONCLUSIONS: This study
      revealed reduced frontal cortical thickness and increased caudate volume in the
      fronto-striatal circuits in young adult smokers compared to nonsmokers. These
      deficits suggest an imbalance between cognitive control (reduced protection
      factors) and reward drive behaviours (increased risk factors) associated with
      nicotine addiction and relapse.

PMID- 25865909
TI  - The relationship between electrocardiographic left ventricular hypertrophy
      criteria and echocardiographic mass in patients undergoing transcatheter aortic
      valve replacement.
AB  - INTRODUCTION: Calcific aortic stenosis (AS) is a common valvular disease among
      the elderly. Often, AS leads to left ventricular hypertrophy (LVH) and symptoms
      of heart failure. Severe AS can be treated by transcatheter aortic valve
      replacement (TAVR). Previous studies have shown that electrocardiogram (ECG)
      criteria for LVH correlate poorly with left ventricular mass (LVM) in
      echocardiography. However, such correlations have not been studied in TAVR
      patients. AIMS: To evaluate ECG LVH criteria as a method of diagnosing and
      quantifying LVH in patients with AS undergoing TAVR. MATERIAL AND METHODS: Twenty
      four patients, with neither pacemaker nor bundle branch block, who had undergone
      pre-TAVR ECG and echocardiography were included. The ECGs were evaluated using
      the Sokolow-Lyon, Romhilt-Estes and Cornell Voltage criteria for LVH as well as
      spatial maximal QRS-T angle and 3D QRS maximal spatial vector. The LVM was
      measured by echocardiography. RESULTS: 15 (63%) patients met the
      echocardiographic threshold for LVH. 7 patients (29%) were positive by the
      Sokolow-Lyon, 5 (21%) by the Romhilt-Estes and 12 (50%) by the Cornell Voltage
      criteria for LVH. There was no correlation between LVM and conventional ECG LVH
      criteria or spatial parameters. QRS duration correlated with LVM (r=0.56,
      R(2)=0.31, p=0.005). However, there was no correlation between QRS duration and
      LVM index or relative wall thickness (RWT). CONCLUSIONS: In TAVR patients, none
      of the ECG LVH criteria should be used for evaluation of LVM. QRS duration is
      moderately correlated to LVM and is the most useful ECG estimate of LVM.

PMID- 25865910
TI  - Psychological distress in the first year after diagnosis of HIV infection among
      women in South Africa.
AB  - Cross-sectional studies on psychological responses associated with an HIV
      diagnosis are replete, but a paucity of research exists to evaluate the changes
      and stability of these responses, particularly among black African women. One
      hundred and five HIV-positive black and coloured women were studied as they
      reported for follow-up health management at the outpatient clinic for infectious
      diseases at Tygerberg Hospital in Cape Town, South Africa. They were assessed at
      baseline and 51 returned for a follow-up interview six months later. Assessments
      involved use of the Mini-International Neuropsychiatric Interview (MINI), the
      Carver Brief COPE, and the Sheehan Disability Scale. Negative life events and
      risk behaviours were also evaluated. Fifty-nine women (56.2%) were diagnosed with
      at least one psychiatric disorder on the MINI at baseline. The most frequent
      diagnosis was major depression (38.1%), followed by dysthymic disorder (22.9%). A
      diagnosis of HIV or AIDS exacerbated the premorbid state of 19% of the women who
      reported a past history of depression. Twelve women (11.4%) were at risk for
      suicide, while 19% met criteria for a clinical diagnosis of post-traumatic stress
      disorder (PTSD) and 6.7% met the diagnosis of generalised anxiety disorders. At
      follow-up, 26 (51%) were diagnosed with at least a psychiatric disorder. Eleven
      (21.6%) met the criteria for major depression, while eight (15.7%) had a past
      history of depression. The number of women with PTSD increased from 19% of the
      total sample at baseline to 29.4% of those interviewed at follow-up. Conversely,
      the number with dysthymia dramatically decreased from 24 women (22.9%) at
      baseline to just one woman at follow-up. The number displaying suicidality also
      decreased from 12 at baseline to four at follow-up. At both baseline and follow
      up, the number and impact of negative life events significantly increased the
      likelihood of major depression persisting or recurring, but this association was
      not found for PTSD. These findings indicate that, over time, there is variability
      in psychiatric morbidity among coloured and black African women living with HIV
      and that a high number of negative life events may increase the likelihood of
      persistent major depression in these women. 

PMID- 25865911
TI  - Motor speed and reaction time in HIV/AIDS patients: a case-control study.
AB  - HIV infection can produce a range of cognitive and behavioural symptoms that
      become more frequent and severe as the immune system deteriorates. This case
      control study assessed the reaction time and the motor speed of Nigerian Africans
      with HIV or AIDS using the simple reaction time and finger-tapping tasks, and
      correlated their performances with their CD4 levels. A total of 288 age-, sex-,
      and level of education-matched subjects, comprising 96 HIV-positive patients with
      symptomatic illness, 96 HIV-positive patients with asymptomatic infection, and 96
      HIV-negative controls, participated in the study. The mean CD4 cell counts of the
      controls, HIV-positive asymptomatic subjects, and HIV-positive symptomatic
      subjects were 682 +/-44, 284 +/-62 and 142 +/-36, respectively (p < 0.05). There
      was no significant difference in the reaction time and motor speeds of the
      asymptomatic HIV-positive subjects and the controls (p > 0.05), but there was
      significant prolongation of reaction time and reduced finger taps among the
      symptomatic HIV-positive subjects (p < 0.01). The cognitive performance was worse
      in subjects with CD4 cell counts less than 200/MUl as compared with subjects with
      CD4 cell counts greater than 200/MUl. We conclude that there is no significant
      prolongation of reaction time and reduced motor speed in asymptomatic HIV
      positive individuals but there is a definite cognitive deterioration with
      progressive reduction in CD4 levels. 

PMID- 25865912
TI  - Understanding visuals in HIV/AIDS education in South Africa: differences between
      literate and low-literate audiences.
AB  - This article reports on a research project aimed at determining the scope and
      nature of differences in picture comprehension between literate and low-literate
      audiences in the context of HIV and AIDS. Structured interviews were held with 30
      low-literate and 24 literate adult speakers of African languages. The responses
      were coded and analysed both qualitatively and quantitatively. Consistent with
      previous research, we found that purely analogical visuals pose relatively few
      interpretation problems across the literacy spectrum. Literate and low-literate
      respondents recognised human beings and familiar analogous objects equally
      successfully. The interpretation of abstract items was problematic for
      respondents at both literacy levels, but relatively more so for low-literate
      respondents. Purely symbolic or conventional abstract elements, such as speech
      and thought balloons, and purely mathematical symbols are difficult for low
      literate individuals since they do not have any analogical residue that will
      trigger relevant meaning aspects of the visual. Metaphors are difficult when they
      require culture-specific knowledge. The results strongly suggest that designers
      should exploit the expressive power of the human body in constructing (abstract)
      meaning. All humans have comparable experiences with associated basic actions and
      bodily expressions. Therefore, facial expressions and body postures and positions
      are powerful in transferring complex messages. We advise that pictorial
      metaphors, art styles that distort objects, complex pictures with partially
      symbolic content, as well as abstract symbols borrowed from written language
      should be omitted where possible. 

PMID- 25865913
TI  - Perceptions of the benefits and affordability of antiretrovirals among HIV
      positive persons in a rural area of South-West Nigeria.
AB  - To assess the affordability of antiretroviral drugs (ARVs) and accessibility to
      treatment for opportunistic infections (OIs) among HIV-1 seropositive persons, we
      used semi-structured interviewer-administered questionnaires to interview 154
      individuals seeking ARV treatment at the Daughter of Charity German Leprosy and
      Tuberculosis Centre in South-West Nigeria. The respondents' mean age was 37 years
      (range 13-65 years) and their average monthly income was NGN9 603 (approx.
      US$73). One hundred and eleven respondents (72.1%) had sought care elsewhere
      before seeking ARV therapy: 67 (60.4%) from private hospitals, 26 (23.4%) from
      public hospitals, 17 (15.3%) from traditional healing homes, and one from an NGO;
      the remaining 43 (27.9%) had not sought medical care before ARV therapy. Thirty
      nine respondents (25.3%) had symptomatic AIDS with evidence of opportunistic
      infections (OIs), and 115 (74.7%) were HIV-1 seropositive only. One hundred and
      twenty-six (81.8%) believed that ARV treatment would prolong their lives, of
      which 27 anticipated a cure for AIDS; eight (11.7%) had no knowledge of the
      benefits of ARV therapy, six (3.9%) had strong fears of stigmatisation and
      discrimination as a consequence of ARV therapy, and four (2.6%) did not express
      any opinion. Sixty-three respondents (40.9%) perceived the cost of ARVs as
      expensive and unaffordable, 58 (37.7%) wanted free drugs, 20 (12.9%) wanted to
      pay a maximum of NGN2 000 (US$15) for monthly supplies (while the actual cost was
      NGN13 000 or US$98), and 13 (8.5%) did not comment. There was a strong
      association between literacy level and knowledge of ARV therapy. The more
      educated tended to have higher incomes and their perception of ARV therapy was
      laudable despite having sought other treatment elsewhere, while the less educated
      tended to earn less and perceived ARV therapy as unaffordable, and therefore had
      not bothered to seek previous treatment. We urge that ARVs be made more
      affordable to enhance their accessibility and treatment compliance, especially
      among lower-income patients. 

PMID- 25865914
TI  - Gendered home-based care in South Africa: more trouble for the troubled.
AB  - This study investigates the experiences of informal caregivers of people living
      with HIV in two semi-rural communities in South Africa. Ethnographic methods were
      used to collect and analyse data on the gendered nature and consequences of home
      based care from 21 primary caregivers and 20 volunteer caregivers as well as 10
      key informants. It was generally women who were poor, unemployed and unmarried
      who combined the care-giving role with their traditional role as homemaker and
      that of being the household head and breadwinner. The caregivers experienced
      physical strains and emotional problems, and were at elevated risk of being
      infected with HIV and TB. Men were largely absent in HIV/AIDS-affected homes and
      usually did not assist because of rigid gendered divisions of labour. Home-based
      care, by creating a disproportionate burden on women, is exacerbating existing
      gender inequities. It is argued that a thorough understanding of how home-based
      care undermines the physical health and psychological wellbeing of already
      vulnerable women is crucial for informing policies on home-based care. Thus,
      there is a need to incorporate gender perspectives when planning and implementing
      home-based care programmes. 

PMID- 25865915
TI  - 'We will eat when I get the grant': negotiating AIDS, poverty and antiretroviral
      treatment in South Africa.
AB  - The maturing HIV epidemic has led to a decline in the health status of many South
      Africans. One result is an increasing number of AIDS-affected poor who qualify
      for a government disability grant. Recent research has drawn attention to the
      unintended conflict that this may present for poor people who might be faced with
      choosing between maintaining health through antiretroviral treatment and
      obtaining money through the state grant. While some evidence suggests that most
      AIDS-affected people would choose antiretroviral treatment over access to a
      disability grant, other evidence suggests that some would rather die than lose
      the grant. This paper is a qualitative exploration of ways that AIDS treatment
      policies and practices and grants for people disabled by AIDS are currently being
      negotiated by people caught in the double-bind of managing their own health and
      income. As South Africa continues to broaden its delivery of antiretroviral
      treatment and AIDS support services, it is important that planners incorporate an
      understanding of how an HIV or AIDS diagnosis in the context of entrenched
      poverty may represent both a threat and a means to financial survival. There is a
      need to consider the 'disinhibiting' effects on HIV prevention and treatment that
      may result when AIDS support services are aimed at addressing the needs of
      individuals as opposed to the needs of highly affected communities. 

PMID- 25865916
TI  - Zambian male adolescents' perceptions about premarital sexual relationships.
AB  - The role adolescent boys play in premarital sexual activities, gender power
      relations, and the reproductive health risks they are exposed to, has received
      little attention in research. This qualitative study has aimed to explore Zambian
      male adolescents' perceptions and expectations about premarital sexual
      relationships. Seven focus group discussions were conducted between November 2000
      and May 2001, in George and Chimwemwe compounds, with 53 boys aged 15 to 19. The
      findings reveal that adolescent premarital sexual relationships are common and
      considered by many boys as a prerequisite to achieving an adult male's autonomy
      and status. The boys viewed themselves as the privileged gender, with greater
      freedom than girls, and were the major decision-makers on sexual matters in
      relationships. The results indicate that traditional values and stereotypical
      gender roles continue to influence Zambian boys' male identity. However, a sense
      of ambiguity among the boys on issues of gender imbalance in premarital
      relationships indicates a potential and preparedness to break with traditional
      trends - a true challenge for public health priorities and interventions. 

PMID- 25865917
TI  - Community impact of HIV status disclosure through an integrated community home
      based care programme.
AB  - The integration of HIV-prevention activities into care has received little
      attention within or outside formal healthcare settings. The contribution of
      community home-based care services in facilitating disclosure of HIV status and
      reducing stigma have also not been described. This study examines the community
      impact of an integrated community home-based care (ICHC) programme on HIV
      prevention efforts and disclosure of status. Quantitative data was collected from
      363 people living with HIV (PLHIV) and 1 028 members of their micro-communities;
      of these, 211 and 586, respectively, were in the ICHC programme (thus
      representing the ICHC-served group) and 152 and 442, respectively, were not in
      the programme (representing the non-served or control group). The micro-community
      group served by the ICHC programme reported significantly more positive attitudes
      towards HIV, better knowledge of HIV, fewer instances of sexually-transmitted
      infections, a tendency for fewer sexual partners, and less perceived risk of
      acquiring HIV than the non-served micro-community group. Also, the micro
      community served by the programme did not show significantly better uptake of
      voluntary counselling and testing than did the non-served micro-community. There
      was no difference in condom-use between the two groups. 

PMID- 25865918
TI  - Knowledge and perception of HIV/AIDS among pregnant women attending antenatal
      clinics in Ogun State, Nigeria.
AB  - Mother-to-child transmission of HIV (MTCT) is responsible for more than 90% of
      the cases of HIV infection in infants and children in sub-Saharan Africa.
      Accurate data on the knowledge and perceptions of HIV/AIDS among women attending
      antenatal clinics in Nigeria are scarce. A cross-sectional survey of 804 women
      attending antenatal clinics in Ogun State, South-West Nigeria was done using
      interviewer-administered questionnaires. Approximately 90% of the women
      respondents had heard of HIV/AIDS, but only about 27% knew HIV could be
      transmitted from mother to child; of those, almost 94% believed in the reality of
      HIV disease; in contrast, the majority (64%) believed they were not at risk of
      HIV infection, and a slightly greater proportion (70%) did not understand the
      benefits of voluntary HIV counselling and testing (VCT). Nonetheless, almost 90%
      of respondents were willing to know their status following health education about
      VCT. Those that were older, attending public hospitals, and with a higher level
      of education had more knowledge and better perceptions about HIV. The results
      suggest an urgent need for public health education on HIV/AIDS and the benefits
      of VCT to control MTCT, particularly targeting young women and those with little
      or no education. 

PMID- 25865919
TI  - Incidence of HIV-1 infection and changes in prevalence of reproductive tract
      infections and sexual risk behaviours: a population-based longitudinal study in
      rural Tanzania.
AB  - This study aimed at describing the prevalence and incidence of HIV-1 and change
      in the prevalence of reproductive tract infections (RTIs) and sexual risk
      behaviours in the rural Kilimanjaro region of Tanzania. Two cross-sectional
      surveys among the total village population of Oria were conducted in 1991 and
      1993. All individuals with a permanent address in the village were registered and
      invited to participate. After informed consent, participants gave blood for HIV-1
      testing. Participants aged 15-44 years were interviewed regarding their socio
      demographic characteristics and sexual risk behaviours and underwent genital
      examination and testing for RTIs. In 1991 and 1993, respectively, 3 239 (83.6%)
      and 2 191 (76.9%) individuals in the village participated. Prevalence of HIV-1
      increased from 1.3% to 1.8%, but the difference was not significant (p = 0.17).
      HIV-1 incidence was 13.0/1000 person-years-at-risk (PYAR) for women and 4.3/1000
      PYAR for men (relative risk was 3.0; 95% CI: 1.12-8.16). There was a significant
      increase in the prevalence of gonorrhoea, bacterial vaginosis and vaginal
      candidiasis (p < 0.001). The percentage of individuals who reported having
      multiple sexual partners during the 12 months preceding the survey increased from
      12.9% to 24.1% (p < 0.001). The results suggest that RTIs and HIV-1 infections
      increased in this population in the early 1990s. Women were at higher risk of HIV
      1 infection as compared to men. Sexual risk behaviours and RTIs may have
      contributed to HIV-1 transmission in this community. The data collected may help
      to inform the future design and evaluation of various intervention measures. 

PMID- 25865920
TI  - Does a linear-received policy of condom promotion result in a myopic approach to
      HIV prevention?
AB  - This commentary discusses how linear models have been utilised to produce HIV
      prevention policies that promote condoms. I examine how discourse on condom
      policy has been used to depict condom-promotion policies as inherently simple and
      rational, scientifically and economically sound, and, by implication, neutral and
      unobjectionable. However, I argue that such policy discourse has produced a
      myopic approach to HIV prevention, wherein the complex reality of prevention is
      disguised, true policy motives are concealed, and alternative approaches are
      marginalised. Although condoms are important in limiting the spread of HIV, the
      policies promoting them often discredit valid alternative policies, ignore
      existing values and beliefs, and create a dichotomy between policy formulators
      and policy subjects. Condom-promotion policies have often been myopically
      accepted because they fit easily into the rational linear-received model. I
      suggest condom-promotion policies should not be pursued uncritically; instead, a
      broad, all-inclusive approach to HIV prevention needs to be adopted. 

PMID- 25865921
TI  - Oxidation of carbon monoxide in basic solution catalyzed by nickel cyano
      carbonyls under ambient conditions and the prototype of a CO-powered alkaline
      fuel cell.
AB  - CO reduces nickel(2+) cyanides in basic solution to form tetrahedral
      Ni(0)(CN)(CO)3(-) or Ni(0)(CN)2(CO)2(2-). Both nickel(0) complexes can be
      oxidized back to nickel(2+) cyanide/hydroxide so that they behave as CO oxidation
      catalysts in basic solution. A primitive fuel cell was constructed to demonstrate
      the feasibility of a CO-powered fuel cell. 

PMID- 25865922
TI  - Infective Endovascular Fibrin Sheath Vegetations-A New Cause of Bacteremia
      Detected by Transesophageal Echocardiogram.
AB  - BACKGROUND/PURPOSE: A fibrin sheath is a circumferential sleeve of endothelium
      that forms around the surface of implanted central venous catheters and
      frequently remains intact within the lumen of the vein after removal of the
      catheters. We describe a new entity of infective endovascular fibrin sheath
      vegetations. METHODS: Records of patients hospitalized and found to have
      echocardiographically identified infective endovascular fibrin sheath vegetations
      at our institution, Cedars Sinai Medical Center, from 2010 to 2014 were reviewed
      for clinical variables of interest. Collected data included medical history,
      physical examination findings, laboratory, microbiology, imaging, a prior history
      of presence of a central venous catheter, treatment, and outcomes. RESULTS:
      Eleven patients (20-77 years old; 6 women, 5 men) were found by transesophageal
      echocardiogram to have fibrin sheaths. All of the infective endovascular fibrin
      sheath vegetations were identified by transesophageal echocardiography, while
      none were seen with transthoracic echocardiography. Eight of 11 patients were
      critically ill, septic, and admitted to the Intensive Care Unit. Six patients
      were intubated and required vasopressor therapy. All cases were treated with long
      term antibiotics, 5 were treated with anticoagulation, and 2 were treated with
      mechanical thrombectomy. Mortality was 36%, with death ranging from 44 to 251
      days after diagnosis. The 90-day hospital readmission rate was 55%. CONCLUSION:
      Infective endovascular fibrin sheath vegetations are not seen with transthoracic
      echocardiogram. They may be overlooked and not seen by transesophageal
      echocardiogram unless the vena cava is adequately imaged. Moreover, fibrin sheath
      vegetations are associated with a high morbidity and mortality. They should be
      treated as a serious endovascular infection and managed with aggressive medical
      or interventional therapies, or both.

PMID- 25865924
TI  - Revisiting Fisher: range size drives the correlation between variability and
      abundance of British bird eggs.
AB  - We evaluate the correlation between intraspecific variation in egg size and
      population size in breeding British birds. Using information on abundance, range
      occupancy, migration status and phylogenetic relationships among species, we show
      that a wider geographical distribution rather than larger population size per se
      best predicts egg size variability. A similar result applies to wing length
      variability. Results from a phylogenetic path analysis suggest that geographical
      variation is the most parsimonious causal explanation for high intraspecific
      variation in common species.

PMID- 25865923
TI  - Medical history for prognostic risk assessment and diagnosis of stable patients
      with suspected coronary artery disease.
AB  - OBJECTIVE: To develop a clinical cardiac risk algorithm for stable patients with
      suspected coronary artery disease based upon angina typicality and coronary
      artery disease risk factors. METHODS: Between 2004 and 2011, 14,004 adults with
      suspected coronary artery disease referred for cardiac imaging were followed: 1)
      9093 patients for coronary computed tomography angiography (CCTA) followed for
      2.0 years (CCTA-1); 2) 2132 patients for CCTA followed for 1.6 years (CCTA-2);
      and 3) 2779 patients for exercise myocardial perfusion scintigraphy (MPS)
      followed for 5.0 years. A best-fit model from CCTA-1 for prediction of death or
      myocardial infarction was developed, with integer values proportional to
      regression coefficients. Discrimination was assessed using C-statistic. The
      validated model was tested for estimation of the likelihood of obstructive
      coronary artery disease, defined as >=50% stenosis, as compared with the method
      of Diamond and Forrester. Primary outcomes included all-cause mortality and
      nonfatal myocardial infarction. Secondary outcomes included prevalent
      angiographically obstructive coronary artery disease. RESULTS: In CCTA-1, best
      fit model discriminated individuals at risk of death or myocardial infarction (C
      statistic 0.76). The integer model ranged from 3 to 13, corresponding to 3-year
      death risk or myocardial infarction of 0.25% to 53.8%. When applied to CCTA-2 and
      MPS cohorts, the model demonstrated C-statistics of 0.71 and 0.77, respectively.
      Both best-fit (C = 0.76; 95% confidence interval [CI], 0.746-0.771) and integer
      models (C = 0.71; 95% CI, 0.693-0.719) performed better than Diamond and
      Forrester (C = 0.64; 95% CI, 0.628-0.659) for estimating obstructive coronary
      artery disease. CONCLUSIONS: For stable symptomatic patients with suspected
      coronary artery disease, we developed a history-based method for prediction of
      death and obstructive coronary artery disease.

PMID- 25865925
TI  - Microneedle applications in improving skin appearance.
AB  - Microneedles (MNs) are micron-sized, minimally invasive devices that breach the
      outermost layer of the skin, the stratum corneum (SC), creating transient,
      aqueous pores in the skin and facilitating the transport of therapeutic molecules
      into the epidermis. Following many years of extensive research in the area of MN
      mediated trans- and intra-dermal drug delivery, MNs are now being exploited in
      the cosmeceutical industry as a means of disrupting skin cell architecture,
      inducing elastin and collagen expression and deposition. They are also being used
      as vehicles to deliver cosmeceutic molecules across the skin, in addition to
      their use in combinatorial treatments with topical agents or light sources. This
      review explores the chronology of microneedling methodologies, which has led to
      the emergence of MN devices, now extensively used in cosmeceutical applications.
      Recent developments in therapeutic molecule and peptide delivery to the skin via
      MN platforms are addressed and some commercially available MN devices are
      described. Important safety and regulatory considerations relating to MN usage
      are addressed, as are studies relating to public perception of MN, as these will
      undoubtedly influence the acceptance of MN products as they progress towards
      commercialisation. 

PMID- 25865926
TI  - Cost of cancer care for patients undergoing chemotherapy: The Elements of Cancer
      Care study.
AB  - AIM: To determine the monthly treatment costs for each element of cancer care in
      patients receiving chemotherapy and to apportion the burden of cost by financing
      agent (Commonwealth, State government, private health insurer, patient). METHODS:
      A cohort of 478 patients (54% breast, 33% colorectal and 13% non-small-cell lung
      cancer) were recruited from 12 centers representing metropolitan and regional
      settings in public and private sectors. Primary data were linked to secondary
      data held in New South Wales state (Admitted Patients and Emergency Department
      Data) and Commonwealth (Medicare and Pharmaceutical Benefits) databases. The
      monthly treatment costs of each element of care and the funding agent were
      calculated from secondary health data. RESULTS: Across all tumor types, the mean
      monthly treatment cost was $4162 (10%-90% quantiles $1018-$8098; range $2853
      [adjuvant colorectal] to $5622 [metastatic lung]), with 54% of this cost borne by
      Commonwealth government, 26% by private health insurers, 14% by State government
      and 6% by patients. The mean monthly costs of treating metastatic disease were
      $1415 greater than those for adjuvant therapy. The mean monthly costs were
      contributed to by inpatient care ($1657, 40%), chemotherapy prescriptions ($1502,
      36%), outpatient care ($452, 11%) and administration of chemotherapy ($364, 9%).
      CONCLUSION: All four funders have a shared incentive to reduce absolute monthly
      treatment costs since their proportional contribution is relatively constant for
      most tumor types and stages. There are opportunities to reduce cancer care costs
      by minimizing the risk of inpatient hospital admissions that arise from
      chemotherapy administration and by recognizing incentives for cost-shifting.

PMID- 25865927
TI  - Sustainability and scale-up of household water treatment and safe storage
      practices: Enablers and barriers to effective implementation.
AB  - Household water treatment and safe storage (HWTS) provides a solution, when
      employed correctly and consistently, for managing water safety at home. However,
      despite years of promotion by non-governmental organizations (NGOs), governments
      and others, boiling is the only method to achieve scale. Many HWTS programs have
      reported strong initial uptake and use that then decreases over time. This study
      maps out enablers and barriers to sustaining and scaling up HWTS practices.
      Interviews were carried out with 79 practitioners who had experience with HWTS
      programs in over 25 countries. A total of 47 enablers and barriers important to
      sustaining and scaling up HWTS practices were identified. These were grouped into
      six domains: user guidance on HWTS products; resource availability; standards,
      certification and regulations; integration and collaboration; user preferences;
      and market strategies. Collectively, the six domains cover the major aspects of
      moving products from development to the consumers. It is important that each
      domain is considered in all programs that aim to sustain and scale-up HWTS
      practices. Our findings can assist governments, NGOs, and other organizations
      involved in HWTS to approach programs more effectively and efficiently. 

PMID- 25865928
TI  - Failure to Recognize Novelty after Extended Methamphetamine Self-Administration
      Results from Loss of Long-Term Depression in the Perirhinal Cortex.
AB  - Exposure to methamphetamine (meth) can produce lasting memory impairments in
      humans and rodents. We recently demonstrated that extended access meth self
      administration results in novel object recognition (NOR) memory deficits in rats.
      Recognition of novelty depends upon intact perirhinal (pRh) cortex function,
      which is compromised by meth-induced downregulation of GluN2B-containing N-methyl
      D-aspartate (NMDA) receptors. NMDA receptors containing this subunit have a
      critical role in pRh long-term depression (LTD), one of the primary physiological
      processes thought to underlie object recognition memory. We hypothesized that
      meth-induced downregulation of GluN2B receptors would compromise pRh LTD, leading
      to loss of NOR memory. We found that meth self-administration resulted in an
      inability to induce pRh LTD following 1 Hz stimulation, an effect that was
      reversed with bath application of the NMDA receptor partial agonist D-cycloserine
      (DCS). In addition, pRh microinfusion of DCS restored meth-induced memory
      deficits. Furthermore, blockade of GluN2B-containing NMDA receptors with Ro 25
      6981 prevented DCS restoration of pRh LTD in meth subjects. Thus, targeting pRh
      LTD may be a promising strategy to treat meth-induced cognitive impairment. 

PMID- 25865929
TI  - Observation of Distressed Conspecific as a Model of Emotional Trauma Generates
      Silent Synapses in the Prefrontal-Amygdala Pathway and Enhances Fear Learning,
      but Ketamine Abolishes those Effects.
AB  - Witnessing pain and distress in others can cause psychological trauma and
      increase odds of developing PTSD in the future, on exposure to another stressful
      event. However, the underlying synaptic process remains unknown. Here we report
      that mice exposed to a conspecific receiving electrical footshocks exhibited
      enhanced passive avoidance (PA) learning when trained 24 h after the exposure.
      The exposure activated neurons in the dorsomedial prefrontal cortex (dmPFC) and
      basolateral amygdala (BLA) and altered synaptic transmission from dmPFC to BLA.
      It increased amplitude, slowed decay of NMDA receptor-mediated currents, and
      generated silent synapses. Administration of sub-anesthetic ketamine immediately
      after the exposure prevented the enhancement of PA learning and silent synapse
      formation. These findings suggest that ketamine can prevent pathophysiological
      consequences of psychological trauma. 

PMID- 25865930
TI  - Endogenous Opioid Signaling in the Medial Prefrontal Cortex is Required for the
      Expression of Hunger-Induced Impulsive Action.
AB  - Opioid transmission and dysregulated prefrontal cortex (PFC) activity have both
      been implicated in the inhibitory-control deficits associated with addiction and
      binge-type eating disorders. What remains unknown, however, is whether endogenous
      opioid transmission within the PFC modulates inhibitory control. Here, we
      compared intra-PFC opioid manipulations with a monoamine manipulation (d
      amphetamine), in two sucrose-reinforced tasks: progressive ratio (PR), which
      assays the motivational value of an incentive, and differential reinforcement of
      low response rates (DRLs), a test of inhibitory control. Intra-PFC
      methylnaloxonium (M-NX, a limited diffusion opioid antagonist) was given to rats
      in a 'low-drive' condition (2-h food deprivation), and also after a motivational
      shift to a 'high-drive' condition (18-h food deprivation). Intra-PFC DAMGO (D
      [Ala2,N-MePhe4, Gly-ol]-enkephalin; a MU-opioid agonist) and d-amphetamine were
      also tested in both tasks, under the low-drive condition. Intra-PFC M-NX nearly
      eliminated impulsive action in DRL engendered by hunger, at a dose (1 MUg) that
      significantly affected neither hunger-induced PR enhancement nor hyperactivity.
      At a higher dose (3 MUg), M-NX eliminated impulsive action and returned PR
      breakpoint to low-drive levels. Conversely, intra-PFC DAMGO engendered 'high
      drive-like' effects: enhancement of PR and impairment of DRL performance. Intra
      PFC d-amphetamine failed to produce effects in either task. These results
      establish that endogenous PFC opioid transmission is both necessary and
      sufficient for the expression of impulsive action in a high-arousal, high-drive
      appetitive state, and that PFC-based opioid systems enact functionally unique
      effects on food impulsivity and motivation relative to PFC-based monoamine
      systems. Opioid antagonists may represent effective treatments for a range of
      psychiatric disorders with impulsivity features.

PMID- 25865932
TI  - Model-based computation of total stressed blood volume from a preload reduction
      manoeuvre.
AB  - Total stressed blood volume is an important parameter for both doctors and
      engineers. From a medical point of view, it has been associated with the success
      or failure of fluid therapy, a primary treatment to manage acute circulatory
      failure. From an engineering point of view, it dictates the cardiovascular
      system's behavior in changing physiological situations. Current methods to
      determine this parameter involve repeated phases of circulatory arrests followed
      by fluid administration. In this work, a more straightforward method is developed
      using data from a preload reduction manoeuvre. A simple six-chamber
      cardiovascular system model is used and its parameters are adjusted to pig
      experimental data. The parameter adjustment process has three steps: (1) compute
      nominal values for all model parameters; (2) determine the five most sensitive
      parameters; and (3) adjust only these five parameters. Stressed blood volume was
      selected by the algorithm, which emphasizes the importance of this parameter. The
      model was able to track experimental trends with a maximal root mean squared
      error of 29.2%. Computed stressed blood volume equals 486 +/- 117 ml or 15.7 +/-
      3.6 ml/kg, which matches previous independent experiments on pigs, dogs and
      humans. The method proposed in this work thus provides a simple way to compute
      total stressed blood volume from usual hemodynamic data.

PMID- 25865931
TI  - Corticotropin-releasing Factor in the Rat Dorsal Raphe Nucleus Promotes Different
      Forms of Behavioral Flexibility Depending on Social Stress History.
AB  - The stress-related neuropeptide, corticotropin-releasing factor (CRF) regulates
      the dorsal raphe nucleus-serotonin (DRN-5-HT) system during stress and this may
      underlie affective and cognitive dysfunctions that characterize stress-related
      psychiatric disorders. CRF acts on both CRF1 and CRF2 receptor subtypes in the
      DRN that exert opposing inhibitory and excitatory effects on DRN-5-HT neuronal
      activity and 5-HT forebrain release, respectively. The current study first
      assessed the cognitive effects of intra-DRN microinfusion of CRF or the selective
      CRF2 agonist, urocortin II in stress-naive rats on performance of an operant
      strategy set-shifting task that is mediated by the medial prefrontal cortex
      (mPFC). CRF (30 ng) facilitated strategy set-shifting performance, whereas higher
      doses of CRF and urocortin II that would interact with CRF2 were without effect,
      consistent with a CRF1-mediated action. This dose decreased 5-HT extracellular
      levels in the mPFC, further supporting a role for CRF1. The effects of CRF were
      then assessed in rats exposed to repeated social stress using the resident
      intruder model. Repeated social stress shifted the CRF effect from facilitation
      of strategy set shifting to facilitation of reversal learning and this was most
      prominent in a subpopulation of rats that resist defeat. Notably, in this
      subpopulation of rats 5-HT neuronal responses to CRF have been demonstrated to
      shift from CRF1-mediated inhibition to CRF2-mediated excitation. Because 5-HT
      facilitates reversal learning, the present results suggest that stress-induced
      changes in the cellular effects of CRF in the DRN translate to changes in
      cognitive effects of CRF. Together, the results underscore the potential for
      stress history to shift cognitive processing through changes in CRF
      neurotransmission in the DRN and the association of this effect with coping
      strategy. 

PMID- 25865933
TI  - The influence of the non-Newtonian properties of blood on blood-hammer through
      the posterior cerebral artery.
AB  - This work investigates a two dimensional numerical analysis of blood hammer
      through the posterior cerebral artery. The non-Newtonian and usual Newtonian
      blood models are compared in the case of blood hammer through the posterior
      cerebral artery to quantify the differences between the models. In this way, a
      validated CFD simulation is used to study non-Newtonian shear-thinning effects of
      blood. The governing equations for the modeling of two-dimensional transient flow
      are solved using a combination of characteristics and central finite difference
      methods, respectively for the hyperbolic and parabolic parts. Herein, the non
      Newtonian viscosity characteristic of blood is incorporated by using the Carreau
      model. To convert the nonlinear terms available in the characteristics equation
      into the linear ones, the Newton-Kantorovich method is implemented. The
      verification and validation of the numerical results are carried out in detail.
      Hemodynamic characteristics of blood hammer through the posterior cerebral artery
      are derived with both the Newtonian and non-Newtonian models, and the results are
      meticulously compared and discussed. The results show that when blood hammer
      occurs, the non-Newtonian properties greatly influence the velocity and shear
      stress profiles. At the early stages of blood hammer, there is a 64% difference
      between magnitudes of wall shear stress in these two models, and the magnitude of
      the wall shear stress for the shear-thinning blood flow is lower than the
      Newtonian one. 

PMID- 25865934
TI  - Modeling malaria and typhoid fever co-infection dynamics.
AB  - Malaria and typhoid are among the most endemic diseases, and thus, of major
      public health concerns in tropical developing countries. In addition to true co
      infection of malaria and typhoid, false diagnoses due to similar signs and
      symptoms and false positive results in testing methods, leading to improper
      controls, are the major challenges on managing these diseases. In this study, we
      develop novel mathematical models describing the co-infection dynamics of malaria
      and typhoid. Through mathematical analyses of our models, we identify distinct
      features of typhoid and malaria infection dynamics as well as relationships
      associated to their co-infection. The global dynamics of typhoid can be
      determined by a single threshold (the typhoid basic reproduction number, R0(T))
      while two thresholds (the malaria basic reproduction number, R0(M), and the
      extinction index, R0(MM)) are needed to determine the global dynamics of malaria.
      We demonstrate that by using efficient simultaneous prevention programs, the co
      infection basic reproduction number, R0, can be brought down to below one,
      thereby eradicating the diseases. Using our model, we present illustrative
      numerical results with a case study in the Eastern Province of Kenya to quantify
      the possible false diagnosis resulting from this co-infection. In Kenya, despite
      having higher prevalence of typhoid, malaria is more problematic in terms of new
      infections and disease deaths. We find that false diagnosis-with higher possible
      cases for typhoid than malaria-cause significant devastating impacts on Kenyan
      societies. Our results demonstrate that both diseases need to be simultaneously
      managed for successful control of co-epidemics. 

PMID- 25865935
TI  - Free-virus and cell-to-cell transmission in models of equine infectious anemia
      virus infection.
AB  - Equine infectious anemia virus (EIAV) is a lentivirus in the retrovirus family
      that infects horses and ponies. Two strains, referred to as the sensitive strain
      and the resistant strain, have been isolated from an experimentally-infected
      pony. The sensitive strain is vulnerable to neutralization by antibodies whereas
      the resistant strain is neutralization-insensitive. The sensitive strain mutates
      to the resistant strain. EIAV may infect healthy target cells via free virus or
      alternatively, directly from an infected target cell through cell-to-cell
      transfer. The proportion of transmission from free-virus or from cell-to-cell
      transmission is unknown. A system of ordinary differential equations (ODEs) is
      formulated for the virus-cell dynamics of EIAV. In addition, a Markov chain model
      and a branching process approximation near the infection-free equilibrium (IFE)
      are formulated. The basic reproduction number R0 is defined as the maximum of two
      reproduction numbers, R0s and R0r, one for the sensitive strain and one for the
      resistant strain. The IFE is shown to be globally asymptotically stable for the
      ODE model in a special case when the basic reproduction number is less than one.
      In addition, two endemic equilibria exist, a coexistence equilibrium and a
      resistant strain equilibrium. It is shown that if R0>1, the infection persists
      with at least one of the two strains. However, for small infectious doses, the
      sensitive strain and the resistant strain may not persist in the Markov chain
      model. Parameter values applicable to EIAV are used to illustrate the dynamics of
      the ODE and the Markov chain models. The examples highlight the importance of the
      proportion of cell-to-cell versus free-virus transmission that either leads to
      infection clearance or to infection persistence with either coexistence of both
      strains or to dominance by the resistant strain. 

PMID- 25865936
TI  - In vitro toxicological evaluation of essential oils and their main compounds used
      in active food packaging: A review.
AB  - Essential oils (EOs) and their main constituent compounds have been extensively
      investigated due to their application in the food industry for improving the
      shelf life of perishable products. Although they are still not available for use
      in food packaging in the market in Europe, considerable research in this field
      has been carried out recently. The safety of these EOs should be guaranteed
      before being commercialized. The aim of this work was to review the scientific
      publications, with a primary focus on the last 10 years, with respect to
      different in vitro toxicological aspects, mainly focussed on
      mutagenicity/genotoxicity. In general, fewer genotoxic studies have been reported
      on EOs in comparison to their main components, and most of them did not show
      mutagenic activity. However, more studies are needed in this field since the
      guidelines of the European Food Safety Authority have not always been followed
      accurately. The mutagenic/genotoxic activities of these substances have been
      related to metabolic activation. Therefore, in vivo tests are required to confirm
      the absence of genotoxic effects. Considering the great variability of the EOs
      and their main compounds, a case-by-case evaluation is needed to assure their
      safe use in food packaging. 

PMID- 25865937
TI  - Screening-level human health risk assessment of toluene and dibutyl phthalate in
      nail lacquers.
AB  - Toluene and dibutyl phthalate (DBP) are found in many consumer products,
      including cosmetics, synthetic fragrances, and nail polish. In 2012, the
      California Environmental Protection Agency evaluated 25 nail products and found
      that 83% of the products that claimed to be toluene-free contained toluene at
      concentrations ranging up to 190,000 ppm, and 14% of the products that claimed to
      be DBP-free contained DBP at concentrations ranging up to 88,000 ppm. We
      conducted a preliminary, screening-level analysis of the potential toluene and
      DBP-related health risks to consumers and professionals based on the medium and
      maximum concentrations of toluene and DBP presented in the 2012 report and
      evaluated dermal and inhalation exposure to a salon patron, nail technician, and
      home user. We concluded that the maximum toluene concentration for the technician
      and home user scenarios exceeded the California MADL, but the estimated air
      concentrations did not exceed the Federal or Cal OSHA PEL. The MADL for DBP was
      exceeded for all user scenarios at both the median and maximum concentrations.
      Using these highly conservative assumptions, exposures above regulatory limits
      could possibly occur during routine use of nail products; further research is
      needed in order to evaluate potential human health risks. 

PMID- 25865939
TI  - Patients' experience of being in intensive care units.
AB  - PURPOSE: The aim of the study was to describe the Jordanian patients' experience
      during their stay in intensive care units (ICUs) and to explore factors that
      contribute to positive and negative experiences. MATERIALS AND METHODS: A
      descriptive, exploratory design was used. The study was conducted at 3 hospitals
      in Jordan. Patients were selected from surgical and medical ICUs within 72 hours
      after transfer to the floor. Data were collected through structured interviews
      using the Intensive Care Experience Questionnaire with 98 patients. RESULTS: Data
      showed high level of awareness among patients to surrounding persons (82.2%) and
      relatives (90.3%). Although 58% of patients perceived pain as a problem during
      their stay, patients' perception of the care as good as it should be was
      generally high (82%). Male and female patients differed significantly in their
      frightening experiences (t=-2.559, P=.01). CONCLUSION: Understanding patients'
      experiences in the ICU would increase nurses' awareness to patients' stressors.
      It would help policy makers in designing structural and process-related care
      activities in a manner that promotes positive patient experiences, which would
      improve quality of care in general and specifically ICU patients' outcome. The
      ICU environment was found to adversely affect patients in many aspects. In
      addition, most patients were able to recall their ICU experience.

PMID- 25865938
TI  - Resveratrol prevents protein nitration and release of endonucleases from
      mitochondria during acetaminophen hepatotoxicity.
AB  - Overdose of acetaminophen (APAP) is a common cause of acute liver injury and
      liver failure. The mechanism involves formation of a reactive metabolite, protein
      binding, oxidative stress and activation of c-Jun N-terminal kinase (JNK),
      mitochondrial dysfunction, and nuclear DNA fragmentation caused by endonucleases
      released from damaged mitochondria. Previous work has shown that the natural
      product resveratrol (RSV) can protect against APAP hepatotoxicity in mice through
      prevention of lipid peroxidation and anti-inflammatory effects. However, these
      earlier studies did not take into consideration several fundamental aspects of
      the pathophysiology. To address this, we treated C57Bl/6 mice with 300 mg/kg APAP
      followed by 50 mg/kg RSV 1.5 h later. Our results confirmed that RSV reduced
      liver injury after APAP overdose in mice. Importantly, RSV did not inhibit
      reactive metabolite formation and protein bindings, nor did it reduce activation
      of JNK. However, RSV decreased protein nitration after APAP treatment, possibly
      through direct scavenging of peroxynitrite. Interestingly, RSV also inhibited
      release of apoptosis-inducing factor and endonuclease G from mitochondria
      independent of Bax pore formation and prevented the downstream nuclear DNA
      fragmentation. Our data show that RSV protects against APAP hepatotoxicity both
      through antioxidant effects and by preventing mitochondrial release of
      endonucleases and nuclear DNA damage.

PMID- 25865940
TI  - Recovery of cough after extubation after coronary artery bypass grafting: A
      prospective study.
AB  - PURPOSE: This study aims to evaluate the effect of intubation for coronary artery
      bypass grafting (CABG) on the cough reflex, an important airway protection
      mechanism. MATERIALS: Eighty-six participants (70 males) underwent cough reflex
      texting (CRT) before intubation for CABG to establish baseline threshold for
      reflexive cough. Cough reflex texting was repeated within 2 hours of extubation
      and every morning and evening thereafter until the participant coughed at
      baseline level, withdrew, or was discharged from hospital. RESULTS: Sixty percent
      of participants had an absent cough reflex at CRT2 (x = 70 minutes). Participants
      varied in time to recovery of cough reflex. By CRT6, only 3 remaining
      participants persisted with an absent cough. Age, sex, or length of intubation
      had no significant impact on the time to recovery of cough reflex (P > .3).
      CONCLUSIONS: Absent cough reflex persists after CABG and may impact patients'
      ability to clear their airway in the event of aspiration. These results could
      contribute to better understanding postextubation dysphagia. More research is
      needed to determine if cough reflex is affected in the wider intensive care unit
      population postextubation and if CRT is a valid tool for detecting silent
      aspiration in this population.

PMID- 25865941
TI  - Improving protein production of indigenous microalga Chlorella vulgaris FSP-E by
      photobioreactor design and cultivation strategies.
AB  - Fish meal is currently the major protein source for commercial aquaculture feed.
      Due to its unstable supply and increasing price, fish meal is becoming more
      expensive and its availability is expected to face significant challenges in the
      near future. Therefore, feasible alternatives to fish meal are urgently required.
      Microalgae have been recognized as the most promising candidates to replace fish
      meal because the protein composition of microalgae is similar to fish meal and
      the supply of microalgae-based proteins is sustainable. In this study, an
      indigenous microalga (Chlorella vulgaris FSP-E) with high protein content was
      selected, and its feasibility as an aquaculture protein source was explored. An
      innovative photobioreactor (PBR) utilizing cold cathode fluorescent lamps as an
      internal light source was designed to cultivate the FSP-E strain for protein
      production. This PBR could achieve a maximum biomass and protein productivity of
      699 and 365 mg/L/day, respectively, under an optimum urea and iron concentration
      of 12.4 mM and 90 MUM, respectively. In addition, amino acid analysis of the
      microalgal protein showed that up to 70% of the proteins in this microalgal
      strain consist of indispensable amino acids. Thus, C. vulgaris FSP-E appears to
      be a viable alternative protein source for the aquaculture industry. 

PMID- 25865942
TI  - Variation among individuals in photoperiod responses: Effects of breeding
      schedule, photoperiod, and age-related photoperiodic experience in birds.
AB  - Many organisms use environmental cues to regulate reproductive function in order
      to time reproduction to coincide with favorable environmental conditions. Whereas
      we understand much about how environmental cues are used to time reproduction, we
      know relatively little about variation among individuals in responsiveness to
      environmental cues. However, this variation among individuals may represent a
      crucial component of a population's capacity to respond to changing environmental
      conditions. In this study, we quantify variation among individuals in photoperiod
      responsiveness of the avian reproductive system and investigate three potential
      underlying sources of this variation in environmental cue responsiveness.
      Specifically, we tested whether age-related photoperiodic experience, strength of
      the photoperiodic cue (day length), and degree of flexibility in breeding
      schedule influenced the degree of variation observed in experimental studies of
      seven species of cardueline finches. Overall, we found a high degree of variation
      among individuals in photoperiod response, and this was influenced by
      experimental photoperiod and breeding schedule. As experimental photoperiod
      became longer, the degree of variation declined. Opportunistic breeders showed
      greater variation in response compared with more seasonal breeders. We found no
      effect of age-related photoperiodic experience in one species for which we could
      examine this factor. The results of this study highlight the extent to which
      individuals can vary in their response to environmental cues and point to both
      species ecology and characteristics of the cue as important influences on the
      degree of this variation.

PMID- 25865943
TI  - CD38 expression predicts poor prognosis and might be a potential therapy target
      in extranodal NK/T cell lymphoma, nasal type.
AB  - No standard chemotherapy regimens have been defined yet for extranodal natural
      killer/T cell lymphoma (ENKTL), and the prognosis of patients with advanced or
      relapsed disease is very poor. Daratumumab, an investigated anti-cancer drug
      targeting CD38, has been of great interest in the treatment of CD38-expressing
      malignancies, especially multiple myeloma. In this study, we reviewed the
      clinical data of 94 patients with ENKTL, investigated the expression of CD38, and
      analyzed the prognostic value of CD38 expression. Forty-seven patients had weak
      expression of CD38, and the other 47 patients had strong expression. The complete
      response (CR) rate was significantly higher in patients who were treated with
      asparaginase-based therapy (83.8 vs. 59.6 %, p = 0.025). There was a trend
      towards higher CR rate in CD38 weak expression group (78.7 vs. 59.6 %, p =
      0.074). At a median follow-up time of 42 months, the 2-year and 5-year
      progression-free survival (PFS) rates were 53.0 and 39.0 %, respectively, and the
      2-year and 5-year overall survival (OS) rates were 68.0 and 58.0 %, respectively.
      In multivariate survival analysis including CD38 expression status, International
      Prognostic Index (IPI) score, local tumor invasion, and chemotherapy regimens, it
      was found that strong expression of CD38 and non-asparaginase-based chemoregimens
      were independent adverse prognostic factors for PFS (p = 0.009 and 0.027,
      respectively), while local tumor invasion and higher IPI score were independent
      adverse prognostic factors for OS (p = 0.002 and 0.035, respectively). In
      subgroup analysis, strong expression of CD38 significantly correlated with
      inferior survival outcomes in patients without local tumor invasion (p = 0.011)
      or with stage I-II disease (p = 0.008). In conclusion, we firstly found that the
      majority of ENKTL cases were CD38 positive, with half had strong expression of
      CD38, which significantly correlated with poor outcomes, indicating the potential
      role of CD38 as a therapy target for ENKTL.

PMID- 25865944
TI  - De novo CSF3R mutation associated with transformation of myeloproliferative
      neoplasm to atypical CML.

PMID- 25865945
TI  - Fulminant pneumococcal bacteraemia revealed by automated digital cell morphology
      analysis (CellaVision DM96).

PMID- 25865946
TI  - How far to go? Determinants of migration distance in land mammals.
AB  - Animal migration is a global phenomenon, but few studies have examined the
      substantial within- and between-species variation in migration distances. We
      built a global database of 94 land migrations of large mammalian herbivore
      populations ranging from 10 to 1638 km. We examined how resource availability,
      spatial scale of resource variability and body size affect migration distance
      among populations. Resource availability measured as normalised difference
      vegetation index had a strong negative effect, predicting a tenfold difference in
      migration distances between low- and high-resource areas and explaining 23% of
      the variation in migration distances. We found a weak, positive effect of the
      spatial scale of resource variability but no effect of body size. Resource-poor
      environments are known to increase the size of mammalian home ranges and
      territories. Here, we demonstrate that for migratory populations as well, animals
      living in resource-poor environments travel farther to fulfil their resource
      needs.

PMID- 25865947
TI  - Mitogenome revealed multiple postdomestication genetic mixtures of West African
      sheep.
AB  - Notable diversity observed within African ovine breeds makes them of great
      interests, but limited studies on genetic origins and domestications remain
      poorly understood. Here, we investigate the evolutionary status of West African
      native breeds, Djallonke and Sahelian sheep using mitogenome sequencing. Compared
      with other ovine mitogenome sequences, West African sheep were revealed a
      Eurasian origin, and the initially tamed sheep breeds in West Africa have been
      genetically mixed with each other and mixed with European breeds. Worldwide
      domestic sheep is deemed the Eurasian origin and migrated west to Europe and
      Africa and east to the Far East, in which dispersed and received selection for
      acclimation to autochthonic environment independently and ultimately evolved into
      different native breeds, respectively. Our results contribute to the
      comprehensive understanding of the domestic sheep origin and reveal multiple
      postdomestication genetic amelioration processes. 

PMID- 25865948
TI  - Plasma levels of glucagon-like peptide 1 and markers of obesity among young and
      healthy adults.
AB  - OBJECTIVE: Glucagon-like peptide 1 (GLP-1)-related pathways may partially explain
      the strong relationship between obesity and type 2 diabetes. We therefore aimed
      to evaluate the relationships between fasting GLP-1 levels, body fat mass and
      other obesity markers in a large sample of young and healthy adults. DESIGN AND
      PATIENTS: Our population-based study included 2096 individuals aged 24-44.
      Exclusion criteria were prevalent cardiovascular disease, diabetes or a body mass
      index (BMI) >35 kg/m(2) . Body fat mass was obtained by bioelectrical impedance
      analysis. Multivariable linear regression models were constructed to assess the
      relationships of GLP-1 with various measures of body composition. RESULTS: Median
      age of our population was 37 years, median BMI 24.1 kg/m(2) and median body fat
      25.1%. A strong positive correlation was observed in age-adjusted models between
      GLP-1 and fat mass in men (beta (95% confidence interval) 1.38 (0.69; 2.07), P <
      0.001) and women (1.27 (0.65; 1.89), P < 0.001) as well as fully adjusted models
      including BMI in men [0.87 (0.27; 1.46), P < 0.01] but not women [0.29 (-0.07;
      0.64), P = 0.11]. The relationships of GLP-1 with BMI for men and women [0.00 (
      0.34; 0.34), P = 0.99] [-0.02 (-0.28; 0.25), P = 0.91] and waist circumference
      [0.43 (-0.45; 1.30), P = 0.34] [0.37 (-0.44; 1.18), P = 0.37], respectively, were
      not significant after multivariable adjustment including fat mass. CONCLUSION:
      Among young and healthy adults, GLP-1 levels are strongly and independently
      related to body fat mass especially in men but not BMI or waist circumference.
      These results raise the hypothesis that GLP-1 may be implicated in body fat mass
      regulation.

PMID- 25865949
TI  - Advantages of a wholly Bayesian approach to assessing efficacy in early drug
      development: a case study.
AB  - This paper illustrates how the design and statistical analysis of the primary
      endpoint of a proof-of-concept study can be formulated within a Bayesian
      framework and is motivated by and illustrated with a Pfizer case study in chronic
      kidney disease. It is shown how decision criteria for success can be formulated,
      and how the study design can be assessed in relation to these, both using the
      traditional approach of probability of success conditional on the true treatment
      difference and also using Bayesian assurance and pre-posterior probabilities. The
      case study illustrates how an informative prior on placebo response can have a
      dramatic effect in reducing sample size, saving time and resource, and we argue
      that in some cases, it can be considered unethical not to include relevant
      literature data in this way.

PMID- 25865950
TI  - Erdheim-Chester disease.
AB  - Erdheim-Chester disease (ECD) is rare form of non-Langerhans cells histiocytosis
      with multiorgan involvement. Individuals are more frequently affected in their
      fifth decade and there is a slight male prevalence. Recent studies have
      demonstrated that ECD patients bare mutations in the proto-oncogene BRAF (and
      more rarely in other genes involved in the MAPK activation pathway), suggesting a
      critical role of this pathway in the pathogenesis and a possible clonal origin of
      the disease. Clinical manifestations are extremely protean and virtually every
      organ system can be affected. The most common clinical features include skeletal
      involvement with typical bilateral osteosclerotic lesions of long bones of the
      lower limbs, diabetes insipidus, cardiovascular involvement with circumferential
      thickening of the aorta ("coated aorta"), and retroperitoneal fibrosis ("hairy
      kidney"). Cardiovascular and central nervous system (CNS) involvement are
      associated with the worst prognosis. Biopsy is necessary to establish a definite
      diagnosis with the identification of CD68+/CD1a-/S100- foamy histiocytes.
      Currently, interferon-alpha is the first-line treatment in ECD, as it has been
      clearly demonstrated to increase overall survival. Anakinra and infliximab have
      also led to encouraging results and should be taken into consideration when
      treatment with interferon-alpha fails. More recently, the BRAF-inhibitor
      vemurafenib has been used in small groups of ECD patients with optimal efficacy
      in all treated cases. Nevertheless, its adverse effects and the scanty data on
      its long-term efficacy and safety still discourage its use as a first-line
      option. Further studies are still warranted to better understand and treat this
      neglected and overlooked disease. 

PMID- 25865951
TI  - The state of autotrophic ethanol production in Cyanobacteria.
AB  - Ethanol production directly from CO2 , utilizing genetically engineered
      photosynthetic cyanobacteria as a biocatalyst, offers significant potential as a
      renewable and sustainable source of biofuel. Despite the current absence of a
      commercially successful production system, significant resources have been
      deployed to realize this goal. Utilizing the pyruvate decarboxylase from
      Zymomonas species, metabolically derived pyruvate can be converted to ethanol.
      This review of both peer-reviewed and patent literature focuses on the genetic
      modifications utilized for metabolic engineering and the resultant effect on
      ethanol yield. Gene dosage, induced expression and cassette optimizat-ion have
      been analyzed to optimize production, with production rates of 0.1-0.5 g L(-1)
      day(-1) being achieved. The current 'toolbox' of molecular manipulations and
      future directions focusing on applicability, addressing the primary challenges
      facing commercialization of cyanobacterial technologies are discussed.

PMID- 25865952
TI  - Ascorbate synthesis in fishes: A review.
AB  - Biosynthesis of ascorbate is known to occur in liver and/or kidney of some
      vertebrates; however, a recent study discovered the expression of l-gulono-gamma
      lactone oxidase, an enzyme essential for ascorbate synthesis, in the brain of the
      African lungfish, Protopterus annectens. This report provides an up-to-date
      review on ascorbate synthesis in fishes and the possible future directions of
      study in view of the discovery of the unusual site of ascorbate biosynthesis.

PMID- 25865953
TI  - Fungal endophytes as prolific source of phytochemicals and other bioactive
      natural products: A review.
AB  - Endophytic fungi are those that live internally in apparently healthy and
      asymptomatic hosts. Endophytic fungi appear to be ubiquitous; indeed, no study
      has yet shown the existence of a plant species without endophytes. High species
      diversity is another characteristic of endophytic mycobiota which is depicted by
      the fact that it is quite common for endophyte surveys to find assemblages
      consisting of more than 30 fungal species per host plant species. Medicinal
      plants had been used to isolate and characterize directly the bioactive
      metabolites. However, the discovery of fungal endophytes inside these plants with
      capacity to produce the same compounds shifted the focus of new drug sources from
      plants to fungi. Bioactive natural products from endophytic fungi, isolated from
      different plant species, are attracting considerable attention from natural
      product chemists and biologists alike which is clearly depicted by the steady
      increase of publications devoted to this topic during the recent years. This
      review will highlight the chemical potential of endophytic fungi with focus on
      the detection of pharmaceutically valuable plant constituents as products of
      fungal biosynthesis. In addition, it will cover newly discovered endophytic fungi
      and also new bioactive metabolites reported in recent years from fungal
      endophytes. It summarizes the up-to-date and comprehensive information on
      bioactive compounds from endophytic fungi by having done a thorough survey of
      literature. 

PMID- 25865954
TI  - Windsor and Perry: reactions of siblings in same-sex and heterosexual couples.
AB  - The U.S. Supreme Court decisions in U.S. v. Windsor (570 U.S. 307) and
      Hollingsworth v. Perry (570 U.S. 399) created a focal point for public discussion
      of marriage equality for same-sex couples. This article reports the results of an
      exploratory study of the reactions of individuals currently or previously in same
      sex couple relationships and a heterosexual sibling who is currently or
      previously married (N = 371) to the Supreme Court decisions. Thematic content
      analysis was used to explore participants' responses to an open-ended question on
      a survey. Reactions of individuals from same-sex couples revealed the following
      themes: (1) longitudinal perspectives on the advancement of rights for same-sex
      couples; (2) emotional responses celebrating the decisions or expressing relief;
      (3) affirmation of their relationship or rights; (4) practical consequences of
      the extension of rights; and (5) minority stress related to anticipation of
      future prejudice or discrimination. Themes in the heterosexual siblings'
      responses were (1) ally support; (2) flat support without emotion or elaboration;
      (3) indifference to or ignorance about the decisions; and (4) disapproval of the
      decisions. These themes are compared and discussed in light of prior research on
      reactions to marriage restriction debates and marriage (in)equality and family
      relationships. 

PMID- 25865955
TI  - Reply.

PMID- 25865956
TI  - Heteronuclear NMR spectroscopic investigations of hydrogen bonding in 2
      (benzo[d]thiazole-2'-yl)-N-alkylanilines.
AB  - The 2-(benzo[d]thiazole-2'-yl)-N-alkylanilines have previously revealed the
      presence of a strong intramolecular hydrogen bond. This in turn gives rise to a
      more complicated multiplet for the protons attached to the carbon adjacent to the
      amino group. This intramolecular hydrogen bond was investigated by a deuterium
      exchange experiment using heteronuclear NMR spectroscopy (1H, 13C, 15N and 2H).
      We observed changes in the multiplet structure and chemical shifts providing
      further evidence that the deuterium replaces the hydrogen in the intramolecular
      hydrogen bond. A time course study of the D2O exchange confirmed the presence of
      a strong hydrogen bond. The comparison of the structures obtained by X-ray
      crystallography showed a very small difference in planarity between the two
      substituted and four-substituted amino compounds. In both the cases, the phenyl
      ring is not absolutely coplanar with the thiazole unit. The existence of this
      intramolecular hydrogen bond in 2-(benzo[d]thiazole-2'-yl)-N-alkylanilines was
      further confirmed by single crystal X-ray crystallography.

PMID- 25865957
TI  - Multifunctional polymer-capped mesoporous silica nanoparticles for pH-responsive
      targeted drug delivery.
AB  - A highly stable modular platform, based on the sequential covalent attachment of
      different functionalities to the surface of core-shell mesoporous silica
      nanoparticles (MSNs) for targeted drug delivery is presented. A reversible pH
      responsive cap system based on covalently attached poly(2-vinylpyridine) (PVP)
      was developed as drug release mechanism. Our platform offers (i) tuneable
      interactions and release kinetics with the cargo drug in the mesopores based on
      chemically orthogonal core-shell design, (ii) an extremely robust and reversible
      closure and release mechanism based on endosomal acidification of the covalently
      attached PVP polymer block, (iii) high colloidal stability due to a covalently
      coupled PEG shell, and (iv) the ability to covalently attach a wide variety of
      dyes, targeting ligands and other functionalities at the outer periphery of the
      PEG shell. The functionality of the system was demonstrated in several cell
      studies, showing pH-triggered release in the endosome, light-triggered endosomal
      escape with an on-board photosensitizer, and efficient folic acid-based cell
      targeting. 

PMID- 25865958
TI  - Limits and potentials of quantum chemical methods in modelling photosynthetic
      antennae.
AB  - Advances in electronic spectroscopies with femtosecond time resolution have
      provided new information on the excitonic processes taking place during the
      energy conversion in natural photosynthetic antennae. This has promoted the
      development of new theoretical protocols aiming at accurately describing the
      properties and mechanisms of exciton formation and relaxation. In this
      perspective, we provide an overview of the quantum chemical based approaches,
      trying to underline both the potentials of the methods and their weaknesses. In
      particular three main aspects will be analysed, the quantum mechanical
      description of excitonic parameters (site energies and couplings), the
      incorporation of environmental effects on these parameters through hybrid
      quantum/classical approaches, and the modelling of the dynamical coupling among
      such parameters and the vibrations of the pigment-protein complex. 

PMID- 25865959
TI  - Efficient heuristics for maximum common substructure search.
AB  - Maximum common substructure search is a computationally hard optimization problem
      with diverse applications in the field of cheminformatics, including similarity
      search, lead optimization, molecule alignment, and clustering. Most of these
      applications have strict constraints on running time, so heuristic methods are
      often preferred. However, the development of an algorithm that is both fast
      enough and accurate enough for most practical purposes is still a challenge.
      Moreover, in some applications, the quality of a common substructure depends not
      only on its size but also on various topological features of the one-to-one atom
      correspondence it defines. Two state-of-the-art heuristic algorithms for finding
      maximum common substructures have been implemented at ChemAxon Ltd., and
      effective heuristics have been developed to improve both their efficiency and the
      relevance of the atom mappings they provide. The implementations have been
      thoroughly evaluated and compared with existing solutions (KCOMBU and Indigo).
      The heuristics have been found to greatly improve the performance and
      applicability of the algorithms. The purpose of this paper is to introduce the
      applied methods and present the experimental results. 

PMID- 25865960
TI  - Intermolecular C-H Bond Activation by a Cationic Iridium(III) Dichloride
      Phenanthroline Complex.
AB  - It is demonstrated that a cationic iridium(III) dichloride phenanthroline complex
      is capable of C-H activation and H/D exchange. It can cleave benzylic and
      unactivated secondary C-H bonds, but exhibits unique selectivity when compared to
      similar systems that have been studied in the condensed phase. Gas-phase rate
      constants and kinetic isotope effects are reported for a variety of substrates
      and the analysis is supported by DFT calculations at the M06/QZVP level.

PMID- 25865961
TI  - Evidence-Based Practice in the Face of Complexity and Comorbidity: A Case Study
      of an Adolescent With Asperger's Syndrome, Anxiety, Depression, and Chronic Pain.
AB  - PROBLEM: Working with clients who present with multiple conditions and
      comorbidities, including mental health difficulties, neurodevelopmental
      disorders, and physical health conditions, requires the therapist to go beyond
      the existing evidence base to make decisions about which specific cognitive
      behavior therapy (CBT) models and resultant treatment approaches to draw on in
      therapy. Routine outcome monitoring across a number of parameters, including goal
      progress, symptom improvement, and changes in functioning, are core to
      maintaining accountability through monitoring the ongoing impact of idiosyncratic
      interventions. METHOD: The case of a young person (age 17 years) who presented
      with mixed anxiety and depression in the context of autism spectrum disorder
      (ASD) and chronic pain are presented. In addition to evidence-based adaptations
      to CBT for clients with ASDs, the therapist selected a cognitive model of low
      self-esteem as a means of collaboratively conceptualizing the client's
      difficulties. FINDINGS AND CONCLUSION: Routine outcome measurement demonstrated
      the effectiveness of the intervention.

PMID- 25865962
TI  - Occipital Nerve Stimulation for Migraine: A Systematic Review.
AB  - Patients who suffer from migraines often report impaired quality of life.
      Occipital nerve stimulation (ONS) is a novel treatment modality for migraines,
      although few systematic reviews have evaluated whether this therapy is
      efficacious. The objective of this study was to evaluate the clinical efficacy
      and safety of ONS for treating migraine through a literature review. We performed
      a literature search to identify studies that investigated ONS for migraine
      treatment. Evidence levels of these studies were assessed by recommendations set
      by the University of Oxford Centre for Evidence-Based Medicine. Five randomized
      controlled trials, 4 retrospective studies, and one prospective study met the
      inclusion criteria. Results from the retrospective studies and case series
      indicated that ONS significantly reduced the pain intensity and the number of
      days with headache in patients with migraine. However, the evidence of ONS
      efficacy established by randomized controlled trials was limited. Improvement in
      the migraine disability assessment (MIDAS) score was more dramatic than
      improvement in the SF-36 score at follow-up. The mean complication incidence of
      ONS was 66% for the reviewed studies. Future clinical studies should optimize and
      standardize the ONS intervention process and identify the relationship among the
      surgical process, efficacy, and complications resulting from the procedure. 

PMID- 25865963
TI  - Dosing algorithms for initiation of immunosuppressive drugs in solid organ
      transplant recipients.
AB  - INTRODUCTION: Starting doses of tacrolimus and ciclosporin are typically chosen
      on a calculated mg/kg bodyweight basis. After initiation of treatment, doses are
      adjusted with therapeutic drug monitoring (TDM). This trial-and-error approach
      has been accepted by most physicians and pharmacists involved in the care of
      transplanted patients. AREAS COVERED: Dosing algorithms have only fairly recently
      been proposed to better individualize the starting dose. This review provides an
      overview of all the currently available dosing algorithms in adult and children
      for the starting dose of ciclosporin, tacrolimus and mycophenolic acid. In these
      algorithms, multiple other covariates influencing the starting dose, such as age,
      hematocrit, comedication and genotype are taken into account. After selecting the
      starting dose with an algorithm and after initiation of treatment, TDM will,
      however, remain necessary. Whether or not implementation of such algorithms will
      improve clinical outcome remains to be demonstrated. EXPERT OPINION: First of all
      an algorithm needs to be validated, against an independent dataset. Second, in a
      prospective study the algorithm should prove to reduce the time to reach the
      target concentration, and to reduce the number of patients with drug
      concentrations (far) outside the therapeutic window. Finally, a clinical trial
      demonstrating a benefit on clinical outcome will be crucial in achieving broad
      acceptance of calculating starting dose using individualized dosing algorithms.

PMID- 25865964
TI  - Regulated necrosis and its implications in toxicology.
AB  - Recent research developments have revealed that caspase-dependent apoptosis is
      not the sole form of regulated cell death. Caspase-independent, but genetically
      regulated, forms of cell death include pyroptosis, necroptosis, parthanatos, and
      the recently discovered ferroptosis and autosis. Importantly, regulated necrosis
      can be modulated by small molecule inhibitors/activators, confirming the cell
      autonomous mechanism of these forms of cell death. The success of small molecule
      mediated manipulation of regulated necrosis has produced great changes in the
      field of cell death research, and has also brought about significant changes in
      the fields of pharmacology as well as toxicology. In this review, we intend to
      summarize the modes of regulated cell death other than apoptosis, and discuss
      their implications in toxicology. 

PMID- 25865965
TI  - The association of infliximab trough levels with disease activity in pediatric
      inflammatory bowel disease.
AB  - OBJECTIVE: Low serum trough levels (TLs) of infliximab (IFX) and antibodies to
      IFX (ATIs) are associated with the loss of therapeutic response in adults with
      inflammatory bowel disease (IBD) receiving IFX. Until now, pediatric data are
      scarce. Therefore, we aimed to cross-sectionally investigate the association
      between ATIs and IFX TLs, and clinical and biochemical disease activity in
      children receiving IFX for IBD. MATERIAL AND METHODS: Children aged <18 years
      receiving IFX maintenance treatment for Crohn's disease (CD) or ulcerative
      colitis (UC) at three Dutch hospitals were included. Prior to two consecutive IFX
      infusions, IFX TLs and ATI levels were measured. Clinical disease activity was
      determined by Pediatric Crohn's Disease Activity Index (PCDAI) and Pediatric
      Ulcerative Colitis Activity Index (PUCAI), for CD and UC, respectively.
      Biochemical disease activity was assessed by serum C-reactive protein (CRP) and
      fecal calprotectin (FC). Clinical remission was defined as a PUCAI or PCDAI score
      of <10. Therapeutic range of IFX was considered 3-7 ug/ml. RESULTS: Thirty-nine
      patients were included (31 CD; 16 females). Median age was 15 years. Median IFX
      TL was 3.5 ug/ml [IQR 2-7]. Subtherapeutic and supratherapeutic TLs were found in
      38% and 23% of children, respectively. ATIs were detected in four patients. A
      correlation was found between IFX TL and CRP [rs = -0.51; p < 0.01] and FC [rs = 
      0.49; p < 0.01]. However, when only clinical disease activity was considered, no
      difference in median TL was found between remission and active disease (resp. 3.5
      ug/ml [IQR 2-5] and 2.3 ug/ml [IQR 0.3-4.6]; p = 0.2). CONCLUSIONS: IFX TLs are
      related to biochemical markers of disease activity. This could provide a
      rationale for monitoring TLs in children receiving IFX for IBD.

PMID- 25865968
TI  - The narrow road to the indigenous rotavirus vaccine.

PMID- 25865966
TI  - Marked antioxidant effect of orange juice intake and its phytomicronutrients in a
      preliminary randomized cross-over trial on mild hypercholesterolemic men.
AB  - BACKGROUND & AIMS: Blond orange juice is the most consumed fruit juice in the
      world. It is a source of hesperidin, a bioavailable flavonoid reported to exhibit
      potential vascular protective actions. However, the specific impact on vascular
      function of Citrus phytomicronutrients, is unknown. For the first time, we
      investigated the effects of blond orange juice compared with a control beverage
      mimicking the composition of orange juice (including Vitamin C but no
      phytomicronutrients), on antioxidant markers, cardiovascular risk factors and
      endothelial function. METHODS: Twenty five male volunteers with two
      cardiovascular risk factors (age over 50 years and LDL-cholesterol between 130
      and 190 mg/L) were enrolled in a randomized cross-over study. They received 3
      times daily 200 mL of either blond orange juice or control beverage for 4 weeks,
      spaced by a 5-week wash-out. Endothelial function (flow mediated dilatation and
      plasma markers), oxidative status, lipid profile and inflammatory markers were
      assessed. RESULTS: Daily intakes of orange juice significantly led to a marked
      antioxidant effect which was correlated to hesperetin plasma levels and related
      with a decrease in reactive oxygen species. A tendency towards reduction of
      endothelial dysfunction and modest increase in plasma apoA-I concentration were
      also observed. This allows further experiments demonstrating the specific effect
      of phytomicronutrients from orange juice. CONCLUSIONS: These findings suggest
      that daily intake of nutritionally relevant dose of blond orange juice may
      contribute for a significant antioxidant effect through the phytochemicals
      contained in. Orange juice may be associated to other healthy foods to achieve a
      significant effect on the vascular function. This study is recorded in
      ClinicalTrials.com as NCT00539916.

PMID- 25865969
TI  - Ureaplasma: current perspectives.
AB  - Ureaplasma species are the most prevalent genital Mycoplasma isolated from the
      urogenital tract of both men and women. Ureaplasma has 14 known serotypes and is
      divided into two biovars- Ureaplasma parvum and Ureaplasma urealyticum. The
      organism has several genes coding for surface proteins, the most important being
      the gene encoding the Multiple Banded Antigen (MBA). The C-terminal domain of MBA
      is antigenic and elicits a host antibody response. Other virulence factors
      include phospholipases A and C, IgA protease and urease. Besides genital tract
      infections and infertility, Ureaplasma is also associated with adverse pregnancy
      outcomes and diseases in the newborn (chronic lung disease and retinopathy of
      prematurity). Infection produces cytokines in the amniotic fluid which initiates
      preterm labour. They have also been reported from renal stone and suppurative
      arthritis. Genital infections have also been reported with an increasing
      frequency in HIV-infected patients. Ureaplasma may be a candidate 'co factor' in
      the pathogenesis of AIDS. Culture and polymerase chain reaction (PCR) are the
      mainstay of diagnosis. Commercial assays are available with improved turnaround
      time. Micro broth dilution is routinely used to test antimicrobial susceptibility
      of isolates. The organisms are tested against azithromycin, josamycin, ofloxacin
      and doxycycline. Resistance to macrolides, tetracyclines and fluoroquinolones
      have been reported. The susceptibility pattern also varies among the biovars with
      biovar 2 maintaining higher sensitivity rates. Prompt diagnosis and initiation of
      appropriate antibiotic therapy is essential to prevent long term complications of
      Ureaplasma infections. After surveying PubMed literature using the terms
      'Ureaplasma', 'Ureaplasma urealyticum' and 'Ureaplasma parvum', relevant
      literature were selected to provide a concise review on the recent developments. 

PMID- 25865970
TI  - An analysis of underlying factors for seasonal variation in gonorrhoea in India:
      a 6-year statistical assessment.
AB  - PURPOSE: A statistical assessment of a disease is often necessary before
      resources can be allocated to any control programme. No literature on seasonal
      trends of gonorrhoea is available from India. OBJECTIVES: The objectives were (1)
      to determine, if any, seasonal trends were present in India (2) to describe
      factors contributing to seasonality of gonorrhoea (3) to formulate approaches for
      gonorrhoea control at the national level. MATERIALS AND METHODS: Seasonal indices
      for gonorrhoea were calculated quarterly in terms of a seasonal index between
      2005 and 2010. Ratio-to-moving average method was used to determine the seasonal
      variation. The original data values in the time-series were expressed as
      percentages of moving averages. Results were also analyzed by second statistical
      method i.e. seasonal subseries plot. RESULTS: The seasonally adjusted average for
      culture-positive gonorrhoea cases was highest in the second quarter (128.61%)
      followed by third quarter (108.48%) while a trough was observed in the first
      (96.05%) and last quarter (64.85%). The second quarter peak was representative of
      summer vacations in schools and colleges. Moreover, April is the harvesting month
      followed by celebrations and social gatherings. Both these factors are associated
      with increased sexual activity and partner change. A trough in first and last
      quarter was indicative of festival season and winter leading to less patients
      reporting to the hospital. CONCLUSION: The findings highlight the immediate need
      to strengthen sexual health education among young people in schools and colleges
      and education on risk-reduction practices especially at crucial points in the
      calendar year for effective gonorrhoea control.

PMID- 25865971
TI  - Utility of whole-cell repetitive extragenic palindromic sequence-based PCR (REP
      PCR) for the rapid detection of nosocomial outbreaks of multidrug resistant
      organisms: experience at a tertiary care center in North India.
AB  - BACKGROUND: There is a huge need to develop molecular typing methods which are
      simple to perform, rapid and cost effective to confirm clonality of nosocomial
      isolates in outbreak situations. OBJECTIVES: The aim of the study was to
      investigate a hospital outbreak of multi-drug resistant (MDR)
      Klebsiellapneumoniae septicemia in a paediatric surgery intensive care unit
      (PSICU) using a repetitive extragenic palindromic polymerase chain reaction (REP
      PCR). MATERIALS AND METHODS: MDR Klebsiella pneumoniae isolates from an outbreak
      of nosocomial sepsis were typed byREP-PCR using consensus primers. Isolates from
      different intensive care units (ICUs) but with similar antibiogram were also
      genotyped for comparison. RESULTS AND CONCLUSION: A cluster of twelve MDR K
      Pneumoniae septicemia cases was identified at the PSICU by genotyping using REP
      PCR. Surveillance cultures failed to pick up any source of infection. REP-PCR was
      found to be a rapid and simple tool for investigation outbreaks in hospitals. Due
      to early detection we could initiate infection control practices with focus on
      hand washing and prevent the further transmission of the organism.

PMID- 25865972
TI  - Emergence of HIV-1 drug-resistant variants in women following antiretroviral
      prophylaxis for the prevention of mother to child transmission.
AB  - PURPOSE: Emergence of drug resistance following HIV prophylaxis has an important
      impact on ART program. OBJECTIVE: To investigate the emergence of drug resistance
      in HIV-1 infected pregnant women. MATERIALS AND METHODS: Fifty-three HIV-1
      infected pregnant women who had received 4-12 weeks of antenatal AZT followed by
      Nevirapine during delivery and Combivir [AZT + 3TC] for 1 week postpartum (group
      1, n = 48) or who come at the time of delivery and received Nevirapine followed
      by Combivir for 1 week (group-2, n = 5) were recruited. Samples were collected
      prior to the start of the prophylaxis and 5-8 weeks postpartum. In addition, a
      third sample was collected between 26-65 weeks postpartum from 7 women.
      Amplification of HIV-1 pol gene and drug resistance analysis was done. RESULT:
      Two (3.8%) women in group-1 showed transmitted drug resistance and they continued
      to show this even at 6 weeks postpartum. One (2%) woman from group-1 showed a
      mutation after 6-8 weeks of prophylaxis. Among the samples collected between 26
      65 weeks postpartum, 3/7 (43%) showed mutations and all these women belong to
      group-1. Women belonging to group-2 didn't show mutation prior to or following
      prophylaxis. CONCLUSION: In contrast to the available data among pregnant women
      with ART prophylaxis, our data showed reduced frequency of mutations following 5
      8 weeks of postpartum but an emergence of mutation later (26-65 weeks). The
      addition of Combivir with the single dose Nevirapine during delivery and the
      early stage of the disease with higher CD4 counts could be the reasons for this.

PMID- 25865973
TI  - High prevalence of class 1 integrons in clinical isolates of methicillin
      resistant Staphylococcus aureus from India.
AB  - INTRODUCTION: Class1 integrons are one of the prevalent mechanisms of antibiotic
      resistance gene transfer in Gram-negative organisms, but their prevalence and
      role in the spread of antibiotic resistance genes in methicillin-resistant
      Staphylococcus aureus (MRSA) is unexplored. The purpose of this study was to
      investigate the prevalence of class 1 integrons in clinical isolates of MRSA.
      MATERIALS AND METHODS: Total 143 MRSA isolates obtained from two different cities
      in India (Pune and Mumbai) were characterized by biochemical tests, and the
      antibiotic sensitivity was performed using the Clinical and Laboratory Standards
      Institute (CLSI) guidelines. The presence of class 1 integrons, sul1/qacE0Delta1
      region of class 1 integron and mecA gene among these isolates was determined by
      polymerase chain reaction (PCR). RESULTS: All 143 isolates were mecA positive and
      coagulase-positive. Overall, 71% of the MRSA isolates carried class 1 integrons;
      58% (45/77) of the isolates obtained from Mumbai and 85% (56/66) of the isolates
      from Pune carried class 1 integrons. In all, 39% of these isolates carried
      sul1/qacEDelta1 region, thus confirming the association of class 1 integrons with
      antibiotic resistance genes. Along with beta-lactam antibiotics the MRSA isolates
      were resistant to several other antibiotics, with resistance to erythromycin,
      ciprofloxacin and trimethoprim-sulfamethoxazole being observed in 75%, 66% and
      60% of the isolates, respectively. CONCLUSION: To the best of our knowledge, this
      is the first report of class 1 integrons in MRSA isolates from India. The study
      provides insights into the prevalence of a novel mechanism adapted by MRSA for
      the propagation of antibiotic resistance genes.

PMID- 25865974
TI  - Comparative evaluation of two rapid Salmonella-IgM tests and blood culture in the
      diagnosis of enteric fever.
AB  - PURPOSE: Enteric fever is a major public health problem in developing countries
      like India. An early and accurate diagnosis is necessary for a prompt and
      effective treatment. We have evaluated the diagnostic accuracy of two Rapid
      Salmonella-IgM tests (Typhidot-IgM and Enteroscreen-IgM) as compared to blood
      culture in rapid and early diagnosis of enteric fever. MATERIALS AND METHODS: A
      total of 2,699 patients' serum samples were tested by Rapid Salmonella-IgM tests
      and blood culture. Patients were divided into two groups. Test group - patients
      with enteric fever and blood culture positives for Salmonella Typhi; and three
      types of Controls, i.e. patients with non-enteric fever illnesses, normal healthy
      controls and patients positive for S. Paratyphi- A. In addition to this we have
      also evaluated the significance of positive Salmonella-IgM tests among blood
      culture-negative cases. RESULTS: The overall sensitivity, specificity, positive
      predictive value (PPV) and negative predictive value (NPV) of the Typhidot-IgM
      test and Enteroscreen-IgM test considering blood culture as gold standard were
      97.29% and 88.13%, 97.40% and 87.83%, 98.18% and 92.03%, 96.15% and 82.27%,
      respectively. Typhidot-IgM test was found to be significantly more sensitive and
      specific as compared to Enteroscreen-IgM. Among blood culture-negative patients,
      Rapid Salmonella-IgM tests detected 72.25% additional cases of enteric fever.
      Although the Rapid Salmonella-IgM tests are meant to diagnose S. Typhi only, but
      these tests detect S. Paratyphi- A also. Thirty-eight patients who were blood
      culture-positive for S. Paratyphi- A were also positive by Rapid Salmonella-IgM
      tests. CONCLUSION: Rapid Salmonella-IgM tests offer an advantage of increased
      sensitivity, rapidity, early diagnosis and simplicity over blood culture.

PMID- 25865975
TI  - Is non-woven fabric a useful method of packaging instruments for operation
      theatres in resource constrained settings?
AB  - INTRODUCTION: Studies have highlighted the advantages and disadvantages of woven
      and non-woven fabrics. The present study assessed the change in resterilisation
      proportion after introduction of non-woven fabric for packaging of instruments
      and to evaluate the cost-effectiveness of non-woven fabrics compared with woven
      fabrics. MATERIALS AND METHODS: The present study is a secondary data analysis of
      resterilisation data collected from November 2009 to August 2013. We calculated
      the proportions (and their 95% confidence intervals) of resterilisation done
      every month. The proportion over time was compared using a Chi-square test for
      trend. We used linear regression analysis to adjust for the number of surgeries
      performed every month. We also compared the cost of woven and non-woven fabrics.
      RESULTS: Of the total 117,335 surgical packets prepared during the study period,
      1900 were resterilised; thus, the overall proportion was 1.62% (95% CI: 1.55% to
      1.69%). The resterilisation proportion was 8.95% (95% CI: 7.73% to 10.17%) in
      November 2009 and was 0.38% (95% CI: 0.16% to 0.62%) in August 2013 (P < 0.001).
      After adjusting for the total number of surgeries conducted every month, we found
      that the number of packets resterilised reduced every month (per month reduction:
      -1.97, 95% CI: -2.76 to -1.18). The total cost (initial preparation and
      resterilisation) for 100 units of woven fabric is INR 6359.41 per month
      (confidence limit estimates: 6228.20 to 6430.62) and for non-woven fabric was INR
      6208.50 (confidence limit estimate: INR 6194.90 to 6223.35) (P < 0.01).
      CONCLUSIONS: The introduction of non-woven spunbond-meltblown-spunbond fabrics
      did reduce the proportion of resterilisation of packaged instruments. The decline
      was sharp and sustained over time, even after accounting for the change in the
      number of procedures. Furthermore, though the switch from woven to non-woven
      fabric was cost-effective in our situation, it may not be directly translated to
      other scenarios.

PMID- 25865976
TI  - Incidence, risk factors, microbiology of venous catheter associated bloodstream
      infections--a prospective study from a tertiary care hospital.
AB  - PURPOSE: Central venous catheters (CVCs) though indispensable in current medical
      and intensive care treatment, also puts patients at risk of catheter related
      infection (CRI) resulting in increased morbidity and mortality. We analysed the
      incidence, risk factors, bacteriological profile and antimicrobial susceptibility
      pattern of the isolates in central venous catheter associated bloodstream
      infection (CVC-BSI) in the intensive care unit (ICU) patients and studied the
      formation of biofilm in CVCs. MATERIALS AND METHODS: The following case control
      study included 115 patients with CVC in situ. Quantitative blood cultures (QBC)
      and catheter tip cultures were performed for the diagnoses. Direct catheter
      staining was done for an early diagnosis by acridine orange (AO) and Gram
      staining methods. Biofilm production in catheters was detected by 'tissue culture
      plate' (TCP) method. The results were analysed using the computer-based program
      statistical package for the social sciences (SPSS). RESULTS: In 25/115 patients,
      definite diagnosis of CVC-BSI was made. The mean age was 48.44 +/- 17.34 years
      (cases) vs 40.10 +/- 18.24 years (controls) and the mean duration of
      catheterisation was 25.72 +/- 8.73 days (cases) vs 11.89 +/- 6.38 days
      (controls). Local signs of infection (erythema, tenderness and oozing) were found
      more significantly in CVC-BSI cases. The AO staining was more sensitive and Gram
      staining of catheters showed higher specificity. Staphylococcus aureus followed
      by Pseudomonas aeruginosa and non-albicans Candida were common CVC-BSI pathogens.
      Multidrug-resistant (MDR) strains were isolated in bacterial agents of CVC-BSI.
      Non-albicans Candida and Enterococcus faecalis showed strong biofilm production.
      CONCLUSION: The incidence of CVC-BSI was 21.73% and the rate was 14.59 per 1000
      catheter days. Prolonged ICU stay and longer catheterisation were major risk
      factors. S. aureus was isolated most commonly in CVC-BSI cases. The menace of
      multidrug resistance and biofilm formation in CVCs is associated with CVC-BSI.

PMID- 25865977
TI  - Impact of informational feedback to clinicians on antibiotic-prescribing rates in
      a tertiary care hospital in Delhi.
AB  - CONTEXT: Antimicrobial use has been associated with increasing antimicrobial
      resistance. There is an urgent need for judicious use of antimicrobials.
      Informational feedback has been shown to result in changes in behavioural
      practices of physicians in certain healthcare settings. We conducted this study
      to see if the passive informational feedback can reduce in antimicrobial usage in
      a tertiary care centre. AIMS: The study was undertaken to evaluate if the
      feedback to clinicians on their own antibiotic prescription results in any change
      in their antibiotic prescription habits. SETTINGS AND DESIGN: The study was
      conducted at a tertiary care setting involving 33 units of different specialties.
      These units were split into 10 groups based on specialty and were allocated
      randomly to the control (16 units) and intervention (17 units) arms of the study.
      This study was a prospective intervention to assess the effect of prescribing
      feedback on clinical prescribing practices. MATERIALS AND METHODS: In the
      intervention arm, information on resistance rates and antibiotic-prescribing
      patterns was provided to all doctors. Behavioural change was assessed by
      comparing baseline prescribing rates of each unit with prescribing rates after
      the intervention. In the control arm, only information on monthly resistance
      rates was provided. STATISTICAL ANALYSIS: Change in the antimicrobial prescribing
      rates in the treatment group was assessed by using a Student's t-test. RESULTS:
      The mean antibiotic use for all the specialties was 189 DDDs/100BDs. The
      prospective intervention did not elicit any effect on the antibiotic prescribing
      practices of the physicians. Low prescribers continued to prescribe antibiotics
      at a low rate, and high prescribers continued to prescribe at a high rate.
      CONCLUSIONS: In view of unfavourable results of passive intervention in the above
      study, active intervention may be more effective.

PMID- 25865978
TI  - Feedback to clinicians on antibiotic prescription habits: how effective are they?

PMID- 25865979
TI  - Vancomycin MIC creep in methicillin-resistant Staphylococcus aureus (MRSA)
      isolates from 2006 to 2010 in a hospital in China.
AB  - PURPOSE: To assess whether vancomycin minimum inhibitory concentration (MIC)
      creeps among clinical isolates of methicillin-resistant Staphylococcus aureus
      (MRSA) in a regional hospital in China. Furthermore, to analyze the causes of
      vancomycin MIC creeps and the relationship between vancomycin MICs and the
      outcome among patients with MRSA infection. MATERIALS AND METHODS: All clinical
      isolates of MRSA from 2006-2010 were retrieved and tested by the broth
      microdilution procedure to determine their vancomycin MIC. Meanwhile, related
      patient records were analyzed. RESULTS: While all isolates were susceptive to
      vancomycin, the percentage of isolates with a vancomycin MIC = 1 mg/L increased
      significantly from 2006 (37.0%) to 2010 (75.7%). Meanwhile, vancomycin usage
      density (DDDs/1000 bed-days) had increased significantly from 2006-2010. Mean
      linear correlation analysis showed a statistically significant positive
      correlation (r = 0.905, P < 0.05) between the consumption of vancomycin and the
      percentage of MRSA isolates with a vancomycin MIC = 1 mg/L. Clinical records
      revealed high vancomycin MIC was associated with a higher microbiologic failure
      rate in MRSA bloodstream infections. CONCLUSIONS: The data demonstrated
      vancomycin MIC creep among clinical isolates in our hospital, and the MIC creep
      may be caused by the increasing usage of vancomycin. Furthermore, the analysis
      strongly suggested this shift of vancomycin MIC within the susceptible range may
      be associated with an increasing probability of treatment failure.

PMID- 25865980
TI  - Spoligotype patterns of Mycobacterium tuberculosis isolated from extra pulmonary
      tuberculosis patients in Puducherry, India.
AB  - PURPOSE: Genotyping studies like spoligotyping are valuable tools in
      understanding the genetic diversity and epidemiology of Mycobacterium
      tuberculosis. Though there are reports of spoligotyping of M. tuberculosis
      isolates from pulmonary specimens from different parts of India, spoligotyping of
      extra pulmonary tuberculosis isolates are very few. Puducherry has not yet
      recorded spoligopatterns of M. tuberculosis from either pulmonary or extra
      pulmonary (EPTB) specimens. The aim of this study is to analyze the spoligotype
      patterns of EPTB strains circulating in Puducherry and neighboring districts of
      Tamil Nadu. MATERIALS AND METHODS: During June 2011 to December 2013, 570 EPTB
      specimens were processed by culturing on to Lowenstein Jensen (LJ) medium and
      automated Mycobacterium Growth Indicator Tube system (MGIT960). Identification of
      M. tuberculosis was carried out as per standard procedures, and MPT 64 antigen
      positivity in a commercial immunochromatography kit. Spoligotyping was carried
      out at National Institute of Research in Tuberculosis (ICMR), Chennai. RESULTS:
      M. tuberculosis was isolated from 67 single EPTB specimens (11.8%) like pus/cold
      abscess (34), TB spine (10), pleural fluid (10), urine (5), tissue bit (2), lymph
      nodes (2), ascitic fluid (2), synovial fluid (1) and endometrial curetting (1).
      Among 67 isolates with 41 spoligopatterns, EAI lineage with 28 isolates (41.8%)
      predominated followed by 18 orphans (26.9%), 10 Beijing (14.9%) and 8 U (11.9%).
      BOVIS1_BCG (ST482), T1-T2 (ST78) and H3 (ST50) were represented by one strain
      each (1.5%). C onclusions: Spoligotyping plays a significant role in the
      epidemiology of tuberculosis. Three spoligotypes, T1-T2 (ST78), EAI6 (ST292) and
      U (ST1429) are reported for the first time in India.

PMID- 25865981
TI  - Development of touch down-multiplex PCR for the diagnosis of toxoplasmosis.
AB  - PURPOSE: The diagnosis of toxoplasmosis is challenging since conventional methods
      like culture and immunofluorescence are not universally available. Serology,
      which is used regularly might be negative during early phase of infection and in
      immunosuppressed patients or may remain positive for a long time. Several
      molecular tests have been used for the diagnosis of toxoplasmosis, but none of
      them have an internal control which would inform us regarding the presence of
      polymerase chain reaction (PCR) inhibitors thus, undermining the confidence of a
      laboratory physician. MATERIALS AND METHODS: We designed a multiplex PCR
      containing primers targeting human beta globin gene which would act as internal
      control and two primers against the B1 gene and 5s gene which aid in sensitive
      detection of T. gondii. RESULTS: Multiplex PCR had a sensitivity of 83.3% and
      specificity of 100%. CONCLUSION: Multiplex PCR may provide a sensitive and
      specific tool for diagnosis of human toxoplasmosis.

PMID- 25865982
TI  - Poor performance characteristics of conventional PCR in detection of respiratory
      syncytial virus-experience of a tertiary care centre in Southern India.
AB  - Respiratory syncytial virus (RSV) is a significant cause of contagious acute
      respiratory infections in children and older adults. Since there are
      contradictory reports regarding the efficacy of different methods to detect RSV,
      we evaluated the performance of the conventional PCR versus real-time PCR in 222
      patients with acute respiratory infections (ARI) recruited between January 2012
      and March 2013. Conventional PCR had a very poor sensitivity of 40% (95% CI: 19.2
      63.9%) and failed to detect RSV in respiratory samples with low viral load. Thus,
      it may be prudent to replace it with real-time PCR to achieve precise diagnosis. 

PMID- 25865983
TI  - Detection of mutations in mtrR gene in quinolone resistant strains of N.
      gonorrhoeae isolated from India.
AB  - BACKGROUND AND OBJECTIVES: Emergence of multi-drug resistant Neisseria
      gonorrhoeae resulting from new genetic mutation is a serious threat in
      controlling gonorrhea. This study was undertaken to identify and characterise
      mutations in the mtrR genes in N.gonorrhoeae isolates resistant to six different
      antibiotics in the quinolone group. MATERIALS AND METHODS: The Minimum inhibitory
      concentrations (MIC) of five quinolones for 64 N.gonorrhoeae isolates isolated
      during Jan 2007-Jun 2009 were determined by E-test method. Mutations in MtrR loci
      were examined by deoxyribonucleic acid (DNA) sequencing. RESULTS: The proportion
      of N.gonorrhoeae strains resistant to anti-microbials was 98.4% for norfloxacin
      and ofloxacin, 96.8% for enoxacin and ciprofloxacin, 95.3% for lomefloxacin.
      Thirty-one (48.4%) strains showed mutation (single/multiple) in mtrR gene. Ten
      different mutations were observed and Gly-45 -> Asp, Tyr-105 -> His being the
      most common observed mutation. CONCLUSION: This is the first report from India on
      quinolone resistance mutations in MtrRCDE efflux system in N.gonorrhoeae. In
      conclusion, the high level of resistance to quinolone and single or multiple
      mutations in mtrR gene could limit the drug choices for gonorrhoea.

PMID- 25865984
TI  - Frequency of extended spectrum beta-lactamase producing urinary isolates of Gram
      negative bacilli among patients seen in a multispecialty hospital in Vellore
      district, India.
AB  - Extended-spectrum beta-lactamase (ESBL) producing strains of Coliform bacilli are
      on the rise and present a major threat especially in India. We assessed the
      frequency of ESBL producers among urinary isolates from patients presenting
      urinary tract infections. ESBL screening was done using Double Disk Synergy Test
      (DDST) and confirmed using E-test and Polymerase Chain Reaction (PCR). With E
      test, 92.2% were positive for ESBL. In PCR, 100% strains were positive for any of
      the three gene targets tested. CTX-M was positive in majority of the strains
      followed by TEM and SHV. Two (3.22%) strains were positive for all the three
      genes; 21% strains were positive for both TEM and CTX-M genes. There was no
      statistically significant difference in the findings of E-test and PCR testing in
      the determination of ESBL producers (Fisher exact test P = 0.15). The strength of
      agreement between them was 'fair' (k = 0.252). Continuous monitoring of ESBL
      producers among Indian strains is important to rationalize the antibiotic policy
      to be followed. 

PMID- 25865985
TI  - Superbugs causing ventilator associated pneumonia in a tertiary care hospital and
      the return of pre-antibiotic era!
AB  - The rise in super bugs causing Ventilator-Associated Pneumonia (VAP) is a major
      cause of mortality and morbidity despite recent advances in management owing to
      the looming 'antibiotic apocalypse'. The aetiology and susceptibility pattern of
      the VAP isolates varies with patient population, type of intensive care unit
      (ICU) and is an urgent diagnostic challenge. The present study carried out for a
      period of one year in a tertiary care hospital, enrolled patients on mechanical
      ventilation (MV) for >=48 hrs. Endotracheal aspirates (ETA) from suspected VAP
      patients were processed by semi quantitative method. Staphylococus aureus,
      members of Enterobacteriaceae were more common in early onset VAP (EOVAP), while
      Nonfermenting Gram negative bacilli (NFGNB) were significantly associated with
      late onset VAP (LOVAP). Most of the isolates were multi drug resistant (MDR)
      super bugs. With limited treatment options left for this crisis situation like
      the pre-antibiotic era; it is an alarm for rational antibiotic therapy usage and
      intensive education programs. 

PMID- 25865986
TI  - A simple and rapid method for the quantitation of secreted hepatitis B virions in
      cell culture models.
AB  - Cell culture models for hepatitis B virus (HBV) remain the mainstay for screening
      and testing the efficacy of anti-hepatitis B virus agents. Gradient-based
      ultracentrifugation followed by Southern Blotting is used for hepatitis B virion
      estimation in cell culture; this method has several limitations. We report the
      development of an assay using a commercially available HBsAg-ELISA plate for
      immunocapture followed by real-time PCR for quantification of hepatitis B virions
      in cell cultures. This assay is rapid, highly sensitive (50 copies/reaction) and
      highly specific for virion-associated DNA. In addition, the assay requires only
      20 MUL of supernatant, allowing scaling down of transfections. 

PMID- 25865987
TI  - A cost-effective carbohydrate fermentation test for yeast using microtitre plate.
AB  - Carbohydrate fermentation test is a well-established technique for speciation of
      bacteria and fungi. However, long incubation period, cost and procedural
      complexity may limit its use. Here, we describe a simple modification of
      conventional carbohydrate fermentation technique using microtitre plate. Thirty
      one yeast isolates were identified based on their fermentation property by
      microtitre plate method and results were compared with conventional method. The
      modified method had 85.7% sensitivity and 100% specificity. The average time
      taken to produce positive reaction was 24 hours. When compared with conventional
      method, modified method reduced turn-around time and cost of processing without
      significant increase in discordant results. 

PMID- 25865988
TI  - Small colony variants of Staphylococcus aureus: a clinical and laboratory
      challenge.

PMID- 25865989
TI  - Emergence of Balamuthia mandrillaris meningoencephalitis in India.
AB  - We report two cases of fatal chronic meningoencephalitis caused by Balamuthia
      mandrillaris in immunocompetent men. Diagnosis of amoebic meningoencephalitis was
      made ante-mortem in one case and postmortem in another by histopathological
      examination and confirmed by demonstration of B. mandrillaris deoxyribonucleic
      acid (DNA) by polymerase chain reaction (PCR). 

PMID- 25865990
TI  - Ludwig's angina by Salmonella Typhi: a clinical dilemma.
AB  - Salmonella Typhi has rarely been associated with focal abscesses; and in
      literature, there is no evidence of its association with abscesses in the neck
      spaces. Ability of Salmonella Typhi to invade and localise in the neck spaces not
      only poses a diagnostic challenge but also underscores the necessity to
      understand the mechanisms that facilitate Salmonella Typhi to establish
      infections at sites completely non-traditional to the organism. 

PMID- 25865991
TI  - Mycotic keratitis due to Engyodontium album: first case report from India.
AB  - Engyodontium album is a rare and an unusual human pathogen. It is a common
      inhabitant of waste and moist material and frequently isolated from substrates
      such as paper, jute, linen and painted walls. This fungus grew within 3 days on
      SDA with chloramphenicol from corneal scrapping of a 70-year-old male farmer with
      a history of trauma by unknown vegetative matter. The fungus can be confused with
      Tritirachium sp and Beauveria sp. 

PMID- 25865992
TI  - Bordetella trematum bacteremia in an infant: a cause to look for.
AB  - Bordetella trematum spp. nov. has been isolated from wounds, ear infections and
      diabetic ulcers. We report a case of a 7-month-old infant with fever, vomiting
      and abnormal body movements with bacteremia caused by this novel species. The
      infant responded to fluoroquinolone and macrolide combination therapy. 

PMID- 25865993
TI  - An unusual case of lung abscess caused by Acremonium species treated with
      itraconazole.
AB  - We present a report of a 37-year-old female with lung abscess due to Acremonium
      species that responded to oral itraconazole. There was a marked clinical as well
      as radiological improvement in patient. To the best of our knowledge, this is the
      first case of lung abscess due to Acremonium species which was treated by oral
      itraconazole. This cost-effective treatment modality proved to be significant in
      improving symptoms as well as morbidity in this patient. 

PMID- 25865994
TI  - Pyonephrosis due to Chryseobacterium gleum: a first case report.
AB  - Chryseobacterium spp are widely distributed in nature but data of their isolation
      from clinical samples is scanty. Here, we report the first case of AmpC producing
      C. gleum causing pyonephrosis in a patient having bilateral nephrolithiasis on
      double J (DJ) stent. The present isolate was resistant to vancomycin,
      erythromycin, clindamycin, carbapenems and ciprofloxacin and susceptible to
      tetracycline and minocycline. The patient was treated with tetracycline and
      recovered without the need for removal of the DJ stent. The environmental
      surveillance carried out to trace the nosocomial origin of the isolate was
      negative. Since antimicrobial susceptibility of this isolate is different from
      previous reports, we emphasise that in vitro susceptibility testing should be
      sought to choose optimal antimicrobial agents for these Nonfermentative Gram
      Negative Bacilli (NFGNBs) with different susceptibility patterns. 

PMID- 25865995
TI  - A rare case of onychomycosis caused by Emericella quadrilineata (Aspergillus
      tetrazonus).
AB  - Onychomycosis is a common chronic nail disorder where dermatophytes are the
      predominant pathogens. However, non-dermatophytic moulds like Aspergillus can
      also be implicated as the causative agents. Herein, we report a rare case of
      onychomycosis due to Emericella quadrilineata ( Aspergillus tetrazonus) in an
      apparently immunocompetent host. 

PMID- 25865996
TI  - Aspergillus infection in urinary tract post-ureteric stenting.
AB  - Fungal infections of the urinary tract are usually encountered following
      prolonged antibiotic use, instrumentation and indwelling urinary catheters. These
      type of infections are mostly seen in immuno-compromised patients. Candida is the
      most common among the fungal infections of urinary tract followed by Aspergillus
      infection. Here is a case report of a 26 year old diabetic female who presented
      with abdominal pain, fever, nausea and vomiting. She had undergone double-J
      stenting 15-20 days back. The cause of the symptoms was not detected till the
      patient underwent C.T Scan-KUB with excretory urography which showed the
      displaced D-J stent. Then on performing replacement of D-J stent, cystoscopy was
      done and the tissue sample was sent for microbiological and histopathological
      examination. On Microbiological examination, Aspergillus flavus was isolated from
      the tissue, which was culprit behind the disease. Patient was then treated with
      anti-fungal drugs, following which she gradually improved. 

PMID- 25865997
TI  - Biofilm formation by bacterial isolates from patients on indwelling medical
      devices.

PMID- 25865998
TI  - Comparison of selective and enrichment media for isolation of vancomycin
      resistant enterococci from rectal swab specimens.

PMID- 25865999
TI  - Urban leptospirosis: a report of two cases.

PMID- 25866000
TI  - An interesting case of pyelonephritis due to inactive and an atypical
      uropathogenic Escherichia coli.

PMID- 25866001
TI  - Human ocular thelaziasis: a case report from Karnataka.

PMID- 25866002
TI  - Clinical and demographic profile of patients reporting for Clostridium difficile
      infection in a tertiary care hospital.

PMID- 25866003
TI  - Prevalence of inducible clindamycin resistance among Staphylococcal isolates in a
      tertiary care hospital in North India.

PMID- 25866005
TI  - Isolation of Francisella tularensis from blood culture.

PMID- 25866004
TI  - Cases of "Measles" in adult age group of St. John's Medical College Boy's Hostel,
      Bangalore, South India.

PMID- 25866006
TI  - Seroprevalence of Chlamydia trachomatis in infertile women in a tertiary care
      hospital: a pilot study.

PMID- 25866007
TI  - Uncommon causes of fungal sinusitis from Eastern India.

PMID- 25866008
TI  - Snippets.

PMID- 25866009
TI  - Molecular epidemiology of methicillin resistant Staphylococcus aureus colonizing
      the anterior Nares of school children of Udupi Taluk: Erratum.

PMID- 25866010
TI  - Coupling acidic organelles with the ER through Ca2+ microdomains at membrane
      contact sites.
AB  - Acidic organelles such as lysosomes serve as non-canonical Ca(2+) stores. The
      Ca(2+) mobilising messenger NAADP is thought to trigger local Ca(2+) release from
      such stores. These events are then amplified by Ca(2+) channels on canonical ER
      Ca(2+) stores to generate physiologically relevant global Ca(2+) signals.
      Coupling likely occurs at microdomains formed at membrane contact sites between
      acidic organelles and the ER. Molecular analyses and computational modelling
      suggest heterogeneity in the composition of these contacts and predicted Ca(2+)
      microdomain behaviour. Conversely, acidic organelles might also locally amplify
      and temper ER-evoked Ca(2+) signals. Ca(2+) microdomains between distinct Ca(2+)
      stores are thus likely to be integral to the genesis of complex Ca(2+) signals. 

PMID- 25866011
TI  - Intramammary infusion of Panax ginseng extract in bovine mammary gland at
      cessation of milking induces changes in the expression of toll-like receptors,
      MyD88 and NF-kB during early involution.
AB  - The purposes of this study were to explore TLR2 and TLR4 participation and MyD88
      and NF-kappaB activation in bovine mammary glands (BMG) treated with Panax
      ginseng (PG) at involution and verify the effect of PG in the cytokine
      expression. Quarters were infused at the end of lactation with PG solution (3
      mg/ml), placebo or kept as uninoculated controls. Cows were slaughtered at 7 d
      after cessation of milking and mammary tissue samples were taken. A significant
      increase of TLR2, TLR4, MyD88, NF-kappaB, IL-1beta, IL-6 and TGF-beta1 mRNA
      expression was observed in PG-treated quarters. Immunostaining of TLR2 and TLR4
      was significantly higher in PG mammary tissues. The percentages of immunopositive
      cells for NF-kappaB-p65 were significantly higher in PG-treated quarters. The BMG
      responded to PG extract components possibly by TLR2 and TLR4 signaling pathway.
      These results provide an insight into potential mechanisms by which PG stimulates
      innate immunity during BMG involution. 

PMID- 25866012
TI  - Dose-related effects of chronic resveratrol administration on neurogenesis,
      angiogenesis, and corticosterone secretion are associated with improved spatial
      memory retention following global cerebral ischemia.
AB  - OBJECTIVES: The polyphenol resveratrol has shown regulatory effects on
      hippocampal neurogenesis, which according to the neurovascular niche hypothesis,
      is likely to involve stimulation of angiogenesis. In rodents, global cerebral
      ischemia leads to selective CA1 neuronal damage, spatial memory impairments,
      lasting changes in corticosterone (CORT) secretion, and increased neurogenesis.
      This study examined dose-related effects of 21-day RSV treatment on markers
      associated with neurogenesis (DCX, PSA-NCAM) and angiogenesis (CD31) in the
      hippocampus at short (7-day) and long-term (85-day) intervals following global
      ischemia. In parallel, post-ischemic and stress-induced CORT levels and spatial
      memory in the Morris water maze were determined. METHODS: Five groups of male
      Wistar rats were included: sham/saline, ischemia/saline, ischemia/1 mg/kg RSV,
      ischemia/10 mg/kg RSV, and sham/10 mg/kg RSV. Changes in expression of plasticity
      markers were paralleled by assessment of basal- and stress-induced CORT
      secretions, and spatial memory performance. RESULTS: Our findings revealed a
      significant attenuation of ischemia-induced DCX/PSA-NCAM expression in RSV
      treated rats, whereas RSV treatment increased angiogenesis in the injured CA1
      region. RSV attenuated CORT levels 3 days post-ischemia and a trend toward
      attenuating CORT secretion in response to 15 minutes restraint stress. Increased
      swimming latencies in the target quadrant during the MWM probe trial in RSV
      treated ischemic rats support beneficial effects of RSV on spatial memory
      retention. DISCUSSION: Our findings uncover time- and dose-related effects of RSV
      and global ischemia on the regulation of hippocampal plasticity. Changes in neuro
      and angiogenesis are consistent with RSV neuroprotective effects, but appear
      independent of RSV regulatory effects on corticosterone secretion.

PMID- 25866013
TI  - Safe male circumcision in Botswana: tension between traditional practices and
      biomedical marketing.
AB  - Botswana has been running Safe Male Circumcision (SMC) since 2009 and has not yet
      met its target. Donors like the US Centers for Disease Control and Prevention and
      Africa Comprehensive HIV/AIDS Partnership (funded by the Gates Foundation) in
      collaboration with Botswana's Ministry of Health have invested much to encourage
      HIV-negative men to circumcise. Demand creation strategies make use of media and
      celebrities. The objective of this paper is to explore responses to SMC in
      relation to circumcision as part of traditional initiation practices. More
      specifically, we present the views of two communities in Botswana on SMC
      consultation processes, implementation procedures and campaign strategies. The
      methods used include participant observation, in-depth interviews with key
      stakeholders (donors, implementers and Ministry officials), community leaders and
      men in the community. We observe that consultation with traditional leaders was
      done in a seemingly superficial, non-participatory manner. While SMC implementers
      reported pressure to deliver numbers to the World Health Organization,
      traditional leaders promoted circumcision through their routine traditional
      initiation ceremonies at breaks of two-year intervals. There were conflicting
      views on public SMC demand creation campaigns in relation to the traditional
      secrecy of circumcision. In conclusion, initial cooperation of local chiefs and
      elders turned into resistance. 

PMID- 25866014
TI  - Effects of metabolic syndrome on the ultrastructure of the femoral nerve in aging
      rats.
AB  - The aim of the present study was to characterize the morphometry of the femoral
      nerve in aging rats with metabolic syndrome compared to controls. Systolic blood
      pressure and fasting plasma glucose were measured, and myelinated and
      unmyelinated fibers in the femoral nerves were quantitatively assessed under
      electron microscopy. Aging rats exposed to a regimen of metabolic syndrome
      developed elevation of plasma glucose concentration, mild hypertension and
      polyneuropathy characterized by a decrease in myelin fiber area, axon diameter,
      myelin sheath thickness and myelin fiber loss in the femoral nerve. The histogram
      of size distribution for myelinated fibers and axons from the aging rats of the
      control group was bimodal. For aging MS animals, the histogram turned out to be
      unimodal. The ultrastructure of unmyelinated fibers and of Schwann cells in 18
      month-old rats was well preserved. Granules of lipofuscin were seen in
      unmyelinated fiber axons of 18-month-old rats with MS. The damage percentage of
      the large myelinated fibers has increased significantly in 18-month-old and 18
      month-old (MS) rats in relation to the controls. No significant difference was
      observed among the groups for the g-ratio. Comparing the three groups, the number
      of neurotubules and neurofilaments in myelinated fibers of 18-month-old rats with
      MS was significantly smaller than for the groups of 18-month-old and 14-month-old
      rats. The overall changes seen in the femoral nerve from aging rats seem minor
      compared to the changes in the aging rats with MS, suggesting that long-term MS
      accelerates the progressive modifications in peripheral nerves that develop in
      old age. 

PMID- 25866015
TI  - Ultra-sensitive all-fibre photothermal spectroscopy with large dynamic range.
AB  - Photothermal interferometry is an ultra-sensitive spectroscopic means for trace
      chemical detection in gas- and liquid-phase materials. Previous photothermal
      interferometry systems used free-space optics and have limitations in efficiency
      of light-matter interaction, size and optical alignment, and integration into
      photonic circuits. Here we exploit photothermal-induced phase change in a gas
      filled hollow-core photonic bandgap fibre, and demonstrate an all-fibre acetylene
      gas sensor with a noise equivalent concentration of 2 p.p.b. (2.3 * 10(-9) cm(-1)
      in absorption coefficient) and an unprecedented dynamic range of nearly six
      orders of magnitude. The realization of photothermal interferometry with low-cost
      near infrared semiconductor lasers and fibre-based technology allows a class of
      optical sensors with compact size, ultra sensitivity and selectivity,
      applicability to harsh environment, and capability for remote and multiplexed
      multi-point detection and distributed sensing. 

PMID- 25866017
TI  - Novel perspectives for hepatitis A virus therapy revealed by comparative analysis
      of hepatitis C virus and hepatitis A virus RNA replication.
AB  - Hepatitis A virus (HAV) and hepatitis C virus (HCV) are two positive-strand RNA
      viruses sharing a similar biology, but causing opposing infection outcomes, with
      HAV always being cleared and HCV establishing persistence in the majority of
      infections. To gain deeper insight into determinants of replication, persistence,
      and treatment, we established a homogenous cell-culture model allowing a thorough
      comparison of RNA replication of both viruses. By screening different human liver
      derived cell lines with subgenomic reporter replicons of HAV as well as of
      different HCV genotypes, we found that Huh7-Lunet cells supported HAV- and HCV
      RNA replication with similar efficiency and limited interference between both
      replicases. HAV and HCV replicons were similarly sensitive to interferon (IFN),
      but differed in their ability to establish persistent replication in cell
      culture. In contrast to HCV, HAV replicated independently from microRNA-122 and
      phosphatidylinositol 4-kinase IIIalpha and beta (PI4KIII). Both viruses were
      efficiently inhibited by cyclosporin A and NIM811, a nonimmunosuppressive analog
      thereof, suggesting an overlapping dependency on cyclophilins for replication.
      However, analysis of a broader set of inhibitors revealed that, in contrast to
      HCV, HAV does not depend on cyclophilin A, but rather on adenosine-triphosphate
      binding cassette transporters and FK506-binding proteins. Finally, silibinin, but
      not its modified intravenous formulation, efficiently inhibited HAV genome
      replication in vitro, suggesting oral silibinin as a potential therapeutic option
      for HAV infections. CONCLUSION: We established a cell-culture model enabling
      comparative studies on RNA replication of HAV and HCV in a homogenous cellular
      background with comparable replication efficiency. We thereby identified new host
      cell targets and potential treatment options for HAV and set the ground for
      future studies to unravel determinants of clearance and persistence.

PMID- 25866018
TI  - Oriented MFI Membranes by Gel-Less Secondary Growth of Sub-100 nm MFI-Nanosheet
      Seed Layers.
AB  - A zeolite membrane fabrication process combining 2D-zeolite nanosheet seeding and
      gel-free secondary growth is described. This process produces selective molecular
      sieve films that are as thin as 100 nm and exhibit record high permeances for
      xylene- and butane-isomers. 

PMID- 25866016
TI  - Antagonistic effects of chloroquine on autophagy occurrence potentiate the
      anticancer effects of everolimus on renal cancer cells.
AB  - Renal cell carcinoma is an aggressive disease often asymptomatic and weakly chemo
      radiosensitive. Currently, new biologic drugs are used among which everolimus, an
      mTOR inhibitor, that has been approved for second-line therapy. Since mTOR is
      involved in the control of autophagy, its antitumor capacity is often limited. In
      this view, chloroquine, a 4-alkylamino substituted quinoline family member, is an
      autophagy inhibitor that blocks the fusion of autophagosomes and lysosomes. In
      the present study, we evaluated the effects of everolimus alone or in combination
      with chloroquine on renal cancer cell viability and verified possible synergism.
      Our results demonstrate that renal cancer cells are differently sensitive to
      everolimus and chloroquine and the pharmacological combination
      everolimus/chloroquine was strongly synergistic inducing cell viability
      inhibition. In details, the pharmacological synergism occurs when chloroquine is
      administered before everolimus. In addition, we found a flow autophagic block and
      shift of death mechanisms to apoptosis. This event was associated with decrease
      of Beclin-1/Bcl(-)2 complex and parallel reduction of anti-apoptotic protein Bcl(
      )2 in combined treatment. At last, we found that the enhancement of apoptosis
      induced by drug combination occurs through the intrinsic mitochondrial apoptotic
      pathway activation, while the extrinsic pathway is involved only partly following
      its activation by chloroquine. These results provide the basis for new
      therapeutic strategies for the treatment of renal cell carcinoma after
      appropriate clinical trial. 

PMID- 25866019
TI  - The early postpartum experience of previously infertile mothers.
AB  - OBJECTIVE: To explore the lived experience of becoming a new mother from the
      unique perspectives of previously infertile women. DESIGN: A descriptive
      phenomenological design was used to extract the fundamental structure of the
      postpartum experience of previously infertile mothers. SETTING: Central Florida.
      PARTICIPANTS: Twelve first-time, previously infertile mothers age 27 to 43 years.
      METHODS: Face-to-face interviews were conducted twice with each participant.
      Recorded interviews were transcribed verbatim and analyzed using Colaizzi's
      approach. RESULTS: Two main themes emerged that described the early postpartum
      experience of first-time, previously infertile mothers: (a) lingering identity as
      infertile and (b) gratitude for the gift of motherhood. Participants reported
      that their lingering identities as infertile and immense gratitude for the gift
      of motherhood propelled them to establish unrealistic expectations to be perfect
      mothers. When they were unable to live up this expectation, they censored their
      feelings of inadequacy, guilt, and shame. CONCLUSION: Findings from this study
      may help to sensitize health care providers to the difficulties faced by
      previously infertile women during their transition to motherhood.

PMID- 25866020
TI  - Modular chemical probes for visualizing and tracking endogenous ion channels.
AB  - Fluorescently labeled, small molecule ligands designed for the labeling and
      tracking of neuronal receptors have become an increasingly popular tool in
      neurobiology. The small size of these probes allows for subcellular imaging of
      proteins in their native state with minimal perturbation of the system. Several
      factors such as the selectivity of the pharmacophore, the size and composition of
      linkers used, and the fluorescence stability of the fluorophore can all influence
      the effectiveness of the small molecule probe. Here we discuss a few key
      molecular targets of this technology including the NMDA receptor, serotonin
      transporter, dopamine transporter, and adenosine receptor due to their
      involvement in numerous neurodegenerative diseases. Future iterations of these
      probes will allow for a better understanding of many important neurological
      proteins as well as the development of new and potent therapeutic drugs. This
      review will cover probe design considerations and discuss examples of specific
      small molecule fluorescent ligands that have been used to study a multitude of
      neuronal receptors through fluorescent imaging. This article is part of the
      Special Issue entitled 'Fluorescent Tools in Neuropharmacology'. 

PMID- 25866021
TI  - Sixth World Workshop on Oral Medicine: historical context.

PMID- 25866022
TI  - Pushing the limits with omega-3 fatty acids.

PMID- 25866024
TI  - Roseimarinus sediminis gen. nov., sp. nov., a facultatively anaerobic bacterium
      isolated from coastal sediment.
AB  - A Gram-stain-negative, facultatively anaerobic, non-motile and pink-pigmented
      bacterium, designated strain HF08(T), was isolated from marine sediment of the
      coast of Weihai, China. Cells were rod-shaped, and oxidase- and catalase
      positive. The isolate grew optimally at 33  degrees C, at pH 7.5-8.0 and with 2
      3% (w/v) NaCl. The dominant cellular fatty acids were iso-C15 : 0, anteiso-C15 :
      0 and iso-C14 : 0. Menaquinone 7 (MK-7) was the major respiratory quinone and the
      DNA G+C content was 44.8 mol%. Phylogenetic analysis based on 16S rRNA gene
      sequences revealed that the isolate was a member of the class Bacteroidia, and
      shared 88-90% sequence similarity with the closest genera Sunxiuqinia,
      Prolixibacter, Draconibacterium, Mariniphaga and Meniscus. Based on the
      phylogenetic and phenotypic evidence presented, a novel species in a new genus of
      the family Prolixibacteraceae is proposed, with the name Roseimarinus sediminis
      gen. nov., sp. nov. The type strain of Roseimarinus sediminis is HF08(T) ( = KCTC
      42261(T) = CICC 10901(T)).

PMID- 25866025
TI  - Mameliella atlantica sp. nov., a marine bacterium of the Roseobacter clade
      isolated from deep-sea sediment of the South Atlantic Ocean.
AB  - A taxonomic study was carried out on strain L6M1-5(T), which was isolated from
      deep-sea sediment collected from the South Atlantic Ocean. The isolate was Gram
      reaction-negative, oxidase-negative and catalase-weakly positive. Growth was
      observed in the presence of 0.5-15% (w/v) NaCl (optimum 3-5%), at 10-41  degrees
      C (optimum 28-30  degrees C), and pH 5.0-10.5 (optimum pH 7.0). The principal
      fatty acids were summed feature 8 (C18 : 1omega7c/omega6c) (84.2%), C18 : 0
      (6.3%), C12 : 1 3-OH (3.2%) and C16 : 0 (2.7%). The polar lipid profile comprised
      phosphatidylethanolamine, phosphatidylglycerol, two unidentified aminolipids, two
      unknown phospholipids and one unknown lipid. Ubiquinone-10 was the major quinone.
      The G+C content of the genomic DNA was 66.0 mol %. Phylogenetic analyses based on
      16S rRNA gene sequences showed that strain L6M1-5(T) belonged to the genus
      Mameliella and shared 95.8% sequence similarity with Mameliella alba JLT354-W(T).
      The combined genotypic and phenotypic data show that strain L6M1-5(T) represents
      a novel species of the genus Mameliella, for which the name Mameliella. atlantica
      sp. nov. is proposed. The type strain is L6M1-5(T) ( = MCCC 1A07531(T) = JCM
      30230(T)).

PMID- 25866026
TI  - Risk and Resilience Factors in the Mental Health and Well-Being of Women with
      Intellectual Disability.
AB  - BACKGROUND: Women with intellectual disability are thought to be at increased
      risk of mental illness, yet little is known about resiliency factors supporting
      women's mental health. This article reports on such factors drawn from a study
      that aimed to address how women with intellectual disability experience their
      mental health and well-being. MATERIALS AND METHODS: Utilizing a broad
      qualitative approach, 25 New Zealand women, aged 21-65 years were interviewed
      about their life from childhood to the present, including, where relevant, their
      experience of mental illness. Data were analysed using a general inductive
      approach. RESULTS: Resiliency factors aligned with the theme 'keeping mentally
      well', subthemes of which were as follows: the importance of relationships with
      family and friends; keeping busy; and autonomy and happiness. Challenges for
      resiliency could be seen in the theme 'mental illness' where subthemes of abuse,
      long-term stress and medication were identified. CONCLUSIONS: Many of the women
      demonstrated remarkable resiliency, despite setbacks and exposure to risks,
      provided they were nested within a supportive context. Those women who
      experienced major mental illness shared evidence of both higher risk factors and
      less support available at crucial times.

PMID- 25866027
TI  - gammaH2AX assay in ex vivo irradiated tumour specimens: A novel method to
      determine tumour radiation sensitivity in patient-derived material.
AB  - PURPOSE: To establish a clinically applicable protocol for quantification of
      residual gammaH2AX foci in ex vivo irradiated tumour samples and to apply this
      method in a proof-of-concept feasibility study to patient-derived tumour
      specimens. MATERIAL AND METHODS: Evaluation of gammaH2AX foci formation and
      disappearance in excised FaDu tumour specimens after (a) different incubation
      times in culture medium, 4Gy irradiation and fixation after 24h (cell recovery),
      (b) 10h medium incubation, 4Gy irradiation and fixation after various time points
      (double strand break repair kinetics), and (c) 10h medium incubation, irradiation
      with graded single radiation doses and fixation after 24h (dose-response). The
      optimised protocol was applied to patient-derived samples of seminoma, prostate
      cancer and glioblastoma multiforme. RESULTS: Post excision or biopsy, tumour
      tissues showed stable radiation-induced gammaH2AX foci values in oxic cells after
      >6h of recovery in medium. Kinetics of foci disappearance indicated a plateau of
      residual foci after >12h following ex vivo irradiation. Fitting the dose-response
      of residual gammaH2AX foci yielded slopes comparable with in situ irradiation of
      FaDu tumours. Significant differences in the slopes of ex vivo irradiated patient
      derived tumour samples were found. CONCLUSION: A novel clinically applicable
      method to quantify residual gammaH2AX foci in ex vivo irradiated tumour samples
      was established. The first clinical results suggest that this method allows to
      distinguish between radiosensitive and radioresistant tumour types. These
      findings support further translational evaluation of this assay to individualise
      radiation therapy.

PMID- 25866028
TI  - An instrument dedicated for modelling of pulmonary radiotherapy.
AB  - BACKGROUND AND PURPOSE: Radiotherapy plays a pivotal role in lung cancer
      treatment. Selection of patients for new (radio)therapeutic options aiming at
      improving outcomes requires reliable and validated prediction models. We present
      the implementation of a prospective platform for evaluation and development of
      lung radiotherapy (proPED-LUNG) as an instrument enabling multidimensional
      predictive modelling. MATERIALS AND METHODS: ProPED-LUNG was designed to comprise
      relevant baseline and follow up data of patients receiving pulmonary radiotherapy
      with curative intent. Patient characteristics, diagnostic and staging
      information, treatment parameters including full dose-volume-histograms, tumour
      control, survival, and toxicity are scored. Besides physician-rated data, a range
      of patient-rated data regarding symptoms and health-related quality-of-life are
      collected. RESULTS: After 18 months of accrual, 315 patients have been included
      (accrual rate, 18 per month). Of the first hundred patients included, 70 received
      conformal (chemo)radiotherapy and 30 underwent stereotactic radiotherapy.
      Compliance at 3 and 6 months follow-up was 96-100% for patient-rated, and 81-94%
      for physician-rated assessments. For data collection, 0.4 FTE were allocated in a
      183 FTE department (0.2%). CONCLUSIONS: ProPED-LUNG is feasible with high
      compliance rates and yields a large amount of high quality prospective disease
      related, treatment-related, patient- and physician-rated data which can be used
      to evaluate new developments in pulmonary radiotherapy.

PMID- 25866029
TI  - MRI integration into treatment planning of head and neck tumors: Can patient
      immobilization be avoided?
AB  - To assess whether deformable registration between CT and MR images can be used to
      avoid patient immobilization, we compared registration accuracy in various
      scenarios, with and without immobilization equipment. Whereas both deformable
      registration and the use of immobilization equipment improved the registration
      accuracy, the combination gave the best alignment. 

PMID- 25866030
TI  - Human brown adipose tissue assessed by simple, noninvasive near-infrared time
      resolved spectroscopy.
AB  - OBJECTIVE: Human brown adipose tissue (BAT) activity has been typically evaluated
      by (18) F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) combined
      with computed tomography (CT). However, FDG-PET/CT has serious limitations (e.g.,
      radiation and cold exposure). This study evaluated BAT density using near
      infrared time-resolved spectroscopy (NIRTRS ), a simple and noninvasive method of
      measuring the indices of tissue hemoglobin concentration [total-Hb] and
      mitochondrial density (us '). METHODS: The NIRTRS parameters at 760, 800, and 830
      nm in the supraclavicular region potentially containing BAT were evaluated.
      First, the NIRTRS parameters were compared at 27  degrees C and during a 2-h cold
      exposure (19  degrees C) in 18 men. Then, NIRTRS parameters at 27  degrees C were
      compared with mean standardized uptake values (SUVmean ) assessed by FDG-PET/CT
      after the 2-h cold exposure (19  degrees C) in 29 men. RESULTS: There was no
      significant difference between the NIRTRS parameters at 27  degrees C and 19
      degrees C. The [total-Hb] and us ' were significantly correlated to SUVmean (r =
      0.73 and r = 0.64, respectively). A receiver operating characteristic analysis
      revealed that the sensitivity (75.0-82.4%), specificity (91.7-100%), and accuracy
      (82.8-86.2%) of the NIRTRS parameters were all good to determine the NIRTRS
      reliability. CONCLUSIONS: Our novel NIRTRS method is noninvasive and simple and
      can reliably assess human BAT density in the supraclavicular region.

PMID- 25866031
TI  - Synthesis of [111]- and {010}-faceted anatase TiO2 nanocrystals from tri-titanate
      nanosheets and their photocatalytic and DSSC performances.
AB  - [111]- and {010}-faceted anatase nanocrystals with controllable crystal size and
      morphology were synthesized from tri-titanate H2Ti3O7 nanosheets by hydrothermal
      reaction. The nanostructures and the formation reaction mechanism of the obtained
      TiO2 nanocrystals were investigated using XRD, FE-SEM, and TEM. Furthermore, the
      photocatalytic and dye-sensitized solar cell (DSSC) performances of the
      synthesized anatase nanocrystals were also characterized. Two types of reactions
      occur in the formation process of the anatase nanocrystals. One is an in situ
      topochemical conversion reaction of the layered titanate structure to an anatase
      structure, and another is the dissolution-deposition reaction on the particle
      surface, which splits the formed nanosheet-like particles into small TiO2
      nanocrystals. The surface photocatalytic activity and the DSSC performance of the
      anatase nanocrystals are dependent on the crystal facet exposed on the particle
      surface, which increases in the order of non-facet < [111]-facet < {010}-facet.
      The increasing order corresponds to the increasing order of the bandgap and
      energy level of the lowest valence band of the anatase nanocrystals. Furthermore,
      the facet of the anatase also affects the DSSC performance, which is enhanced in
      the order of non-facet < [111]-facet < {010}-facet. 

PMID- 25866032
TI  - Long-term safety and performance of the orbital atherectomy system for treating
      calcified coronary artery lesions: 5-Year follow-up in the ORBIT I trial.
AB  - BACKGROUND/PURPOSE: The ORBIT I trial, a first-in-man study, was conducted to
      evaluate the safety and performance of the orbital atherectomy system (OAS) in
      treating de novo calcified coronary lesions. METHODS/MATERIALS: Fifty patients
      were enrolled between May and July 2008 based on several criteria, and were
      treated with the OAS followed by stent placement. The safety and performance of
      the OAS were evaluated by procedural success, device success, and overall major
      adverse cardiovascular event (MACE) rates, including cardiac death, myocardial
      infarction (MI) and need for target lesion revascularization (TLR). Our
      institution enrolled and treated 33 of the 50 patients and continued follow-up
      for 5 years. RESULTS: Average age was 54 years and 91% were males. Mean lesion
      length was 15.9 mm. Device success was 100%, and average number of orbital
      atherectomy devices (OAD) used per patient was 1.3. Stents were placed directly
      after OAS in 31/32 patients (96.9%). All stents (average stent per lesion 1.1)
      were successfully deployed with 0.3% residual stenosis. The overall cumulative
      MACE rate was 6.1% in-hospital, 9.1% at 30 days, 12.1% at 6 months, 15.2% at 2
      years, 18.2% at 3 years and 21.2% at 5 years (4 total cardiac deaths). None of
      the patients had Q-wave MIs. Angiographic complications were observed in 5
      patients. No flow/slow flow due to distal embolization was observed. CONCLUSIONS:
      The ORBIT I trial suggests that OAS treatment continues to offer a safe and
      effective method to change compliance of calcified coronary lesions to facilitate
      optimal stent placement in these difficult-to-treat patients.

PMID- 25866033
TI  - Identification of a novel dehydration responsive gene, drp10, from the African
      clawed frog, Xenopus laevis.
AB  - During periods of environmental stress a number of different anuran species
      employ adaptive strategies to promote survival. Our study found that in response
      to dehydration (i.e., loss of total body water content), the African clawed frog
      (Xenopus laevis) increased the expression of a novel gene (drp10) that encodes a
      structural homolog of the freeze-responsive FR10 protein found in wood frogs.
      Similar to FR10, the DRP10 protein was found to also contain a highly conserved N
      terminal cleavable signal peptide. Furthermore, DRP10 was found to have high
      structural homology to the available crystal structures of type A and E
      apolipoproteins in Homo sapiens, and a type IV LS-12 anti-freeze protein in the
      longhorn sculpin, Myoxocephalus octodecemspinosis. In response to dehydration,
      the transcript expression of drp10 was found to increase 1.52 +/- 0.16-fold and
      1.97 +/- 0.11-fold in response to medium (15%) and high (30%) dehydration
      stresses in the liver tissue of X. laevis, respectively, while drp10 expression
      increased 2.12 +/- 0.12-fold and 1.46 +/- 0.16-fold in kidney tissue. Although
      the molecular function of both dehydration-responsive DRP10 and the freeze
      responsive FR10 have just begun to be elucidated, it is likely that both are frog
      specific proteins that likely share a similar purpose during water-related
      stresses.

PMID- 25866034
TI  - The relation between long-term cortisol levels and the metabolic syndrome in HIV
      infected patients.
AB  - OBJECTIVE: Patients infected with the human immunodeficiency virus (HIV) have an
      increased risk of metabolic complications such as dyslipidaemia, insulin
      resistance and hypertension; symptoms that are also associated with an excess of
      the hormone cortisol. We studied the relationship between long-term cortisol
      levels and metabolic syndrome (MetS) in HIV-infected patients. DESIGN: Cross
      sectional study performed at the outpatient clinic of infectious diseases of the
      Erasmus MC, University Medical Center Rotterdam, the Netherlands. METHODS:
      Fasting blood samples and anthropometric data were collected in 126 HIV-infected
      patients. An ELISA-based technique was used to determine long-term cortisol
      levels in scalp hair. Cortisol levels were compared to 191 healthy controls.
      RESULTS: A higher risk of MetS was observed in HIV patients with a low hair
      cortisol (odds ratio lower vs upper tertile 4.23, P = 0.04). Hair cortisol levels
      were not significantly different between HIV patients and healthy controls (16.4
      pg/mg vs 13.5 pg/mg; P = 0.14). CONCLUSION: The risk of MetS was significantly
      higher in HIV-infected patients in the lowest hair cortisol group compared with
      patients in the highest hair cortisol group. This finding contrasts with results
      from studies in uninfected individuals where a high cortisol level in hair is
      associated with metabolic syndrome. The results of this study suggest that these
      metabolic complications might be related to relative cortisol hypersensitivity in
      HIV patients.

PMID- 25866036
TI  - Bipolar doping of double-layer graphene vertical heterostructures with
      hydrogenated boron nitride.
AB  - Using first-principles calculations, we examined the bipolar doping of double
      layer graphene vertical heterostructures, which are constructed by hydrogenated
      boron nitride (BN) sheets sandwiched into two parallel graphene monolayers. The
      built-in potential difference in hydrogenated BN breaks the interlayer symmetry,
      resulting in the p- and n-type doping of two graphene layers at 0.83 and -0.8 eV,
      respectively. By tuning the interlayer spacing between the graphene and
      hydrogenated BN, the interfacial dipole and screening charge distribution can be
      significantly affected, which produces large modulations in band alignments,
      doping levels and tunnel barriers. Furthermore, we present an analytical model to
      predicate the doping level as a function of the average interlayer spacing. With
      large interlayer spacings, the "pillow effect" (Pauli repulsion at the highly
      charge overlapped interface) is diminished and the calculated Dirac point shifts
      are in good accordance with our prediction models. Our investigations suggest
      that this double-layer graphene heterostructures constructed using two
      dimensional Janus anisotropic materials offer exciting opportunities for
      developing novel nanoscale optoelectronic and electronic devices. 

PMID- 25866037
TI  - Limitations of component therapy for massive haemorrhage: is whole blood the
      whole solution?

PMID- 25866038
TI  - Tapentadol--the evidence so far.

PMID- 25866035
TI  - Alcohol consumption and the risk of renal cancers in the European prospective
      investigation into cancer and nutrition (EPIC).
AB  - Epidemiologic studies have reported that moderate alcohol consumption is
      inversely associated with the risk of renal cancer. However, there is no
      information available on the associations in renal cancer subsites. From 1992
      through to 2010, 477,325 men and women in the European Prospective Investigation
      into Cancer and Nutrition cohort were followed for incident renal cancers (n =
      931). Baseline and lifetime alcohol consumption was assessed by country-specific,
      validated dietary questionnaires. Information on past alcohol consumption was
      collected by lifestyle questionnaires. Hazard ratios (HRs) and 95% confidence
      intervals (CIs) were estimated from Cox proportional hazard models. In
      multivariate analysis, total alcohol consumption at baseline was inversely
      associated with renal cancer; the HR and 95% CI for the increasing categories of
      total alcohol consumption at recruitment versus the light drinkers category were
      0.78 (0.62-0.99), 0.82 (0.64-1.04), 0.70 (0.55-0.90), 0.91 (0.63-1.30),
      respectively, (ptrend  = 0.001). A similar relationship was observed for average
      lifetime alcohol consumption and for all renal cancer subsites combined or for
      renal parenchyma subsite. The trend was not observed in hypertensive individuals
      and not significant in smokers. In conclusion, moderate alcohol consumption was
      associated with a decreased risk of renal cancer. 

PMID- 25866039
TI  - Oxygen therapy and anaesthesia: too much of a good thing?

PMID- 25866040
TI  - Haemostatic profile of reconstituted blood in a proposed 1:1:1 ratio of packed
      red blood cells, platelet concentrate and four different plasma preparations.
AB  - The concept of haemostatic resuscitation implies early and high-volume plasma
      transfusion. We investigated the haemostatic profile of reconstituted whole blood
      prepared in a 1:1:1 ratio of blood, platelets and plasma. This consisted of
      packed red blood cells, platelet concentrate and four different plasma variants:
      fresh frozen; solvent-detergent; lyophilised quarantine; and lyophilised
      methylene blue-inactivated plasma. Haematocrit, platelet count, endogenous
      thrombin potential and coagulation factor activity were significantly lower in
      reconstituted blood compared with citrated whole blood (p < 0.01). Except for
      lyophilised methylene blue-inactivated plasma, no substantial differences between
      plasma variants in coagulation factor activity, endogenous thrombin potential and
      standard coagulation tests were observed. After reconstitution, haematocrit and
      platelet counts were slightly above recommended transfusion triggers, most
      thromboelastometry (ROTEM((r))) parameters were within the normal range and
      fibrinogen concentrations were between 1.57 g.l(-1) and 1.91 g.l(-1).
      Reconstitution of whole blood in a 1:1:1 ratio resulted in significant dilution
      of haematocrit and platelet count, but values remained above limits recommended
      by transfusion guidelines. Fibrinogen concentrations of reconstituted whole blood
      were also significantly reduced, and these were below the threshold value for
      supplementation recommended by recent guidelines.

PMID- 25866041
TI  - Safety guideline: reducing the risk from cemented hemiarthroplasty for hip
      fracture 2015: Association of Anaesthetists of Great Britain and Ireland British
      Orthopaedic Association British Geriatric Society.
AB  - Concise guidelines are presented for the preparation and conduct of anaesthesia
      and surgery in patients undergoing cemented hemiarthroplasty for hip fracture.
      The Working Party specifically considered recent publications highlighting
      complications occurring during the peri-operative period. The advice presented is
      based on previously published advice and clinical studies.

PMID- 25866042
TI  - Some LMAs are stiffer than others.

PMID- 25866043
TI  - Decontaminating Ebola-infected ultrasound probes.

PMID- 25866044
TI  - Is organ donation helping us to make better decisions?

PMID- 25866045
TI  - A reply.

PMID- 25866046
TI  - A reply.

PMID- 25866047
TI  - Capnography for bougie placement.

PMID- 25866048
TI  - Tramadol and delirium.

PMID- 25866049
TI  - Could extubation in the PACU reduce awareness and improve theatre utilisation?

PMID- 25866050
TI  - Disposable vs re-usable C-MAC (r) blades.

PMID- 25866051
TI  - Tea trolleys and infection control.

PMID- 25866052
TI  - Are current skin antisepsis guidelines too superficial?

PMID- 25866053
TI  - Safe general anaesthesia without secure intravenous access.

PMID- 25866054
TI  - Ovarian cancer immunotherapy using PD-L1 siRNA targeted delivery from folic acid
      functionalized polyethylenimine: strategies to enhance T cell killing.
AB  - Adoptive T cell immunotherapy is a promising treatment strategy for epithelial
      ovarian cancer (EOC). However, programmed death ligand-1 (PD-L1), highly
      expressed on EOC cells, interacts with programmed death-1 (PD-1), expressed on T
      cells, causing immunosuppression. This study aims to block PD-1/PD-L1
      interactions by delivering PD-L1 siRNA, using various folic acid (FA)
      functionalized polyethylenimine (PEI) polymers, to SKOV-3-Luc EOC cells, and
      investigate the sensitization of the EOC cells to T cell killing. To enhance
      siRNA uptake into EOC cells, which over express folate receptors, PEI is modified
      with FA or PEG-FA so that siRNA is complexed into nanoparticles with folate
      molecules on the surface. PEI modification with a single functional group lowers
      the polymer cytotoxicity compared to unmodified PEI. FA-conjugated polymers
      increase siRNA uptake into SKOV-3-luc cells and decrease unspecific uptake into
      monocytes. All polymers result in 40% to 50% PD-L1 protein knockdown.
      Importantly, SKOV-3-Luc cells treated with either PEI-FA or PEI- polyethylene
      glycol (PEG)-FA/PD-L1 siRNA complexes are up to twofold more sensitive to T cell
      killing compared to scrambled siRNA treated controls. These findings are the
      first to demonstrate that PD-L1 knockdown in EOC cells, via siRNA/FA-targeted
      delivery, are able to sensitize cancer cells to T cell killing. 

PMID- 25866056
TI  - A high-cholesterol diet enriched with polyphenols from Oriental plums (Prunus
      salicina) improves cognitive function and lowers brain cholesterol levels and
      neurodegenerative-related protein expression in mice.
AB  - Ageing accompanied by a decline in cognitive performance may be a result of the
      long-term effects of oxidative stress on neurologic processes. It has been shown
      that high-cholesterol contents in the blood and brain may lead to the deposition
      of the beta-amyloid (Abeta) protein in the brain, which damages brain cells. The
      present study was designed to observe the effect of polyphenol-rich Oriental
      plums on cognitive function and cerebral neurodegeneration-related protein
      expression in mice that were fed a high-cholesterol diet for 5 months. The study
      consisted of four groups: the control (Ctrl) group, which was fed the American
      Institute of Nutrition (AIN)-93M diet; the high cholesterol (HC) group, which was
      fed the AIN-93M diet with 5% cholesterol; the high cholesterol + low Oriental
      plum (LOP) group, which was fed the AIN-93M diet with 5% cholesterol and 2%
      Oriental plum powder; and the high cholesterol + high Oriental plum (HOP) group,
      which was fed the AIN-93M diet with 5% cholesterol and 5% Oriental plum powder.
      Measurements of cognitive function were assessed using the Morris water maze, and
      the mRNA expression of cholesterol hydroxylase (Cyp46), Abeta and beta-secretase
      1 (BACE1) were analysed. The results showed that cholesterol concentrations in
      both the blood and the brain were significantly higher in the HC group than in
      the Ctrl and HOP groups at the end of the trial. The high-cholesterol diet per se
      produced significant cognitive deficits, which were accompanied by a
      significantly increased mRNA expression of Cyp46, BACE1, Abeta and 24
      hydroxycholesterol in the brain cortex and hippocampus. However, all of these
      variables were non-significantly increased in the HOP group as compared to the
      Ctrl group. In conclusion, incorporating polyphenol-enriched Oriental plum into a
      high-cholesterol diet can ameliorate some of the symptoms of neurodegenerative
      conditions.

PMID- 25866055
TI  - Endosymbiont evolution: predictions from theory and surprises from genomes.
AB  - Genome data have created new opportunities to untangle evolutionary processes
      shaping microbial variation. Among bacteria, long-term mutualists of insects
      represent the smallest and (typically) most AT-rich genomes. Evolutionary theory
      provides a context to predict how an endosymbiotic lifestyle may alter
      fundamental evolutionary processes--mutation, selection, genetic drift, and
      recombination--and thus contribute to extreme genomic outcomes. These predictions
      can then be explored by comparing evolutionary rates, genome size and stability,
      and base compositional biases across endosymbiotic and free-living bacteria.
      Recent surprises from such comparisons include genome reduction among uncultured,
      free-living species. Some studies suggest that selection generally drives this
      streamlining, while drift drives genome reduction in endosymbionts; however, this
      remains an hypothesis requiring additional data. Unexpected evidence of selection
      acting on endosymbiont GC content hints that even weak selection may be effective
      in some long-term mutualists. Moving forward, intraspecific analysis offers a
      promising approach to distinguish underlying mechanisms, by testing the null
      hypothesis of neutrality and by quantifying mutational spectra. Such analyses may
      clarify whether endosymbionts and free-living bacteria occupy distinct
      evolutionary trajectories or, alternatively, represent varied outcomes of similar
      underlying forces.

PMID- 25866059
TI  - The future of AIDS in Africa: lessons from two scenario projects.
AB  - Scenario planning or futures studies have their origin in military planning, but
      have also been used with great success in the private sector, most notably in the
      energy industry. UNAIDS and the South African financial services group
      Metropolitan each recently published a set of scenarios regarding the future
      impact of HIV/AIDS in Africa and South Africa, respectively. This article reviews
      the methodologies and outcomes of those two studies, and highlights the many
      lessons to be gleaned for HIV-related health planning and policy-making in
      general. This is the first time that a comparative study has been done on
      scenario planning that refers to HIV in particular, and the findings may inspire
      the conceptualisation of futures studies elsewhere. 

PMID- 25866058
TI  - Microphthalmia-associated transcription factor expression levels in melanoma
      cells contribute to cell invasion and proliferation.
AB  - Microphthalmia-associated transcription factor (MITF) is a nodal point in
      melanoma transcriptional network that regulates dozens of genes with critical
      functions in cell differentiation, proliferation and survival. Highly variable
      MITF expression levels exist in tumor cell subpopulations conferring marked
      heterogeneity and plasticity in the tumor tissue. A model has been postulated
      whereby lower MITF levels favour cell invasion and suppress proliferation,
      whereas high levels stimulate differentiation and proliferation. Additionally,
      MITF is considered to be a prosurvival gene and a lineage addiction oncogene in
      melanoma. Herein, we review how MITF expression may affect the melanoma phenotype
      with consequences on the survival, invasion and metastasis of melanoma cells, and
      we discuss the research challenges. 

PMID- 25866057
TI  - Assessment of tumor response to oxygen challenge using quantitative diffusion MRI
      in an animal model.
AB  - PURPOSE: To assess tumor response to oxygen challenge using quantitative
      diffusion magnetic resonance imaging (MRI). MATERIALS AND METHODS: A well
      characterized Dunning R3327-AT1 rat prostate cancer line was implanted
      subcutaneously in the right thigh of male Copenhagen rats (n = 8). Diffusion
      weighted images (DWI) with multiple b values (0, 25, 50, 100, 150, 200, 300, 500,
      1000, 1500 s/mm(2) ) in three orthogonal directions were obtained using a
      multishot FSE-based Stejskal-Tanner DWI sequence (FSE-DWI) at 4.7T, while rats
      breathed medical air (21% oxygen) and with 100% oxygen challenge. Stretched
      exponential and intravoxel incoherent motion (IVIM) models were used to calculate
      and compare quantitative diffusion parameters: diffusion heterogeneity index
      (alpha), intravoxel distribution of diffusion coefficients (DDC), tissue
      diffusivity (Dt), pseudo-diffusivity (Dp), and perfusion fraction (f) on a voxel
      by-voxel basis. RESULTS: A significant increase of alpha (73.9 +/- 4.7% in air
      vs. 78.1 +/- 4.5% in oxygen, P = 0.0198) and a significant decrease of f (13.4 +/
      3.7% in air vs. 10.4 +/- 2.7% in oxygen, P = 0.0201) were observed to accompany
      oxygen challenge. Correlations between f and alpha during both air and oxygen
      breathing were found; the correlation coefficients (r) were -0.90 and -0.96,
      respectively. Positive correlations between Dt and DDC with oxygen breathing (r =
      0.95, P = 0.0003), f and DDC with air breathing were also observed (r = 0.95, P =
      0.0004). CONCLUSION: Quantitative diffusion MRI demonstrated changes in tumor
      perfusion in response to oxygen challenge.

PMID- 25866060
TI  - Breaching cultural silence: enhancing resilience among Ugandan orphans.
AB  - Cultural silence is frequently the outcome of deep-seated taboos regarding adults
      talking to children about sex and death. This paper examines the impact of
      cultural silence on the resilience of children orphaned by AIDS in Uganda.
      Cultural silence is often linked with denial. This article explores the
      complexities of cultural silence in terms of its causes, justifications and
      impacts. The findings from two small, in-depth qualitative studies among orphans
      who were being supported by community-based organisations in Kampala illustrate
      the impacts of cultural silence and disclosure on the coping ability of orphaned
      children. The first study involved 11 children orphaned by AIDS (four boys and
      seven girls, aged 12 to 17 years) and four parents widowed by AIDS (two men and
      two women) who were themselves living with HIV. (None of the parents interviewed
      were related to the orphans in the study.) In the second study, 10 HIV-positive
      mothers (aged 25 to 40) and nine children (six boys and three girls, aged 11 to
      18) with HIVpositive mothers were interviewed. The discussion examines the
      findings by using a model of resilience, centred on the concepts of closeness and
      competence as conditions for coping. Cultural silence emerges as a risk factor
      that increases children's vulnerability through undermining both closeness and
      competence, while disclosure and openness - the breaching of cultural silence -
      are revealed as protective factors that may enhance resilience among children. 

PMID- 25866061
TI  - Reaching disenfranchised youth and mobile populations in Ghana through voluntary
      counselling and testing services for HIV.
AB  - This paper documents the evaluation of a 20-month project to provide voluntary
      counselling and testing (VCT) to a mobile population of youth surrounding the
      Agbogbloshie market in Accra, Ghana. The specific objectives of the evaluation
      were to determine: 1) to what extent targets for providing VCT services to the
      specified population were reached; 2) how HIV prevalence among clients compared
      to that of the general population; 3) to what extent former clients self-reported
      behaviour change; and 4) whether useful lessons could be drawn regarding fees,
      hours, and location of services, as well as use of peer educators to increase use
      of VCT services among the target population. Various methodologies, including
      questionnaires, focus group discussions, a review of the service statistics and
      an exit poll of clients were used to evaluate the project. The service statistics
      demonstrated that the project exceeded the life-of-project target for number of
      clients by nearly 40%. Prevalence for the VCT client population (aged 15-25) was
      higher than for the general population (aged 15-24), although the gender
      differentials were similar. Focus group data suggested that clients may have
      adopted behaviour changes as a result of VCT. Finally, focus group discussions
      and VCT service trends showed that the high number of clients was largely
      influenced by three factors: services being free, location and hours of services
      being convenient to the target population, and use of peer educators to promote
      the services. In addition, the evaluation highlighted the importance of the
      counselling component of VCT, even as counselling can get short-changed at the
      expense of HIV testing when large numbers of clients are involved. The evaluation
      stressed the need to appropriately remunerate peer educators for their work
      whenever possible. Finally, VCT programmes continue to face challenges such as:
      HIV stigma as a barrier to people coming to be counselled and tested;
      insufficient availability of medication, support and services for HIVpositive
      clients; and difficulty of ensuring the sustainability of VCT programmes. 

PMID- 25866062
TI  - Modelling the relationship between antiretroviral treatment and HIV prevention:
      limitations of the Spectrum AIDS Impact Model in a changing policy environment.
AB  - This paper shows how two publicly available epidemiological modelling packages,
      namely the Spectrum AIDS Impact Model and the ASSA2003 AIDS and Demographic
      Model, predict very different impacts from rolling out highly active
      antiretroviral treatment (HAART) on new HIV infections. Using South Africa as a
      case study, it shows that the ASSA2003 model predicts a significant drop in new
      HIV infections as HAART is rolled out, whereas the Spectrum model assumes that
      HAART does not have a preventative impact (and in fact generates a small increase
      in new HIV infections). Users will thus draw different conclusions about the
      public health benefits of HAART depending on which modelling package they use.
      Despite being presented as a policy-oriented modelling tool capable of exploring
      'what if' questions about the impact of different policy choices, the Spectrum
      model is illequipped to do so with regard to a HAART rollout. Unlike Spectrum,
      ASSA2003 is more flexible and its assumptions are clear. Better modelling and
      more information (including about the relationship between HAART and sexual risk
      behaviour) is required to develop appropriate public-policy modelling for the
      HAART era. 

PMID- 25866063
TI  - Socio-demographic and clinical features of HIV-positive outpatients at a clinic
      in south-west Nigeria.
AB  - Despite the increasing prevalence of HIV in Nigeria, there is scarce knowledge
      about the spectrum of HIV-related diseases in the country. This paper documents
      the profile of outpatients seen at the HIV clinic of the Lagos University
      Teaching Hospital (LUTH), between January 2005 and January 2006. The socio
      demographic data and clinical features of the patients were documented and their
      HIV status was determined using dual enzyme immunoassays; a series of other tests
      included a CD4 cell count. In all, 240 males and 345 females were included,
      giving a male to female ratio of 1:1.4. Mean age of the participants overall was
      35.9 years (SD = 9.1 years); male patients had a significantly higher mean age
      than female patients (39.2 vs 35.9 years). Traders comprised the largest
      occupational group and appear to be a group at high risk of exposure to HIV who
      may therefore require targeted interventions. Heterosexual intercourse was the
      presumed mode of exposure to HIV in over 90% of cases. The majority of
      outpatients had advanced immunosuppression at presentation, with fever, weight
      loss, diarrhoea and skin lesions being the most common presenting events.
      Pulmonary tuberculosis was the most frequent AIDS indicator condition. Females
      had a significantly higher mean CD4 count at presentation than did males
      (263/mm(3) vs 214/mm(3)). Apart from the apparent predominance of traders and the
      relatively high proportion of patients with dermatitis, the profile of LUTH
      HIV/AIDS patients is similar to what has been reported from other centres in sub
      Saharan Africa. 

PMID- 25866064
TI  - Child participation in research: reflections on ethical challenges in the
      southern African context.
AB  - This article reflects on several challenges that particular cultural, socio
      economic and catastrophic factors (such as the HIV epidemic) pose to ethical
      practice in research involving child participation in a region such as southern
      Africa. With reference to concrete situations, we discuss research practices in
      relation to: countering the widespread power disparity between adults and
      children; ensuring the authenticity of children's evidence; obtaining informed
      consent; ensuring non-malfeasance and beneficence; and preserving the anonymity
      of participants and their sources. Within the authors' own research experience,
      selected elements of practice that have been helpful in addressing these issues
      are offered. It is hoped that the article may have relevance not only in the
      southern African context, but also for developing countries elsewhere. 

PMID- 25866065
TI  - Knowledge of HIV/AIDS, sexual behaviour and prevalence of sexually transmitted
      infections among female students of the University of Buea, Cameroon.
AB  - The study investigates the cognitive effect of knowledge and protective practices
      on the prevalence of HIV and some sexually transmitted infections (STIs) among
      female students of the University of Buea, Cameroon. A cross-sectional study
      involving the analysis of a questionnaire completed by 522 female students and
      the voluntary testing of 108 sexually active females for HIV, syphilis, Chlamydia
      and gonorrhoea was carried out. Knowledge of the protective effects of
      abstinence, condom-use and fidelity were independent of sexual practices (OR =
      0.86, p = 0.611, phi = 0.22; OR = 1.26, p = 0.213, phi = 0.05; and OR = 1.18, p =
      0.344, phi = 0.029, respectively). The prevalence of HIV, syphilis, Chlamydia and
      gonorrhoea among the participants tested was 3.9%, 6.1%, 24.1% and 30.1%,
      respectively. We conclude that relatively high prevalence of STIs among female
      students of the University of Buea stems from inadequate knowledge of the major
      modes of STI/HIV transmission and inadequate use of preventive methods. 

PMID- 25866066
TI  - The making of vulnerabilities: understanding the differentiated effects of HIV
      and AIDS among street traders in Warwick Junction, Durban, South Africa.
AB  - The end of apartheid in South Africa has led to political-economic transition,
      the deregulation of cities, and increased population mobility, with growing
      numbers of people living and working in sub-standard and 'informal' urban
      conditions. These processes have created a fertile terrain for the rapid spread
      of HIV, especially in the province of KwaZulu-Natal. Few studies have considered
      how the HIV epidemic's outcomes are interacting with other societal processes,
      such as globalisation and urbanisation, or how these processes collectively
      converge with place-specific conditions to expose, drive and compound
      vulnerabilities to HIV and AIDS. This paper links an analysis of the political
      economy of South Africa's HIV epidemic with findings from an ethnographic case
      study with street traders in Warwick Junction, the largest trading hub in Durban,
      KwaZulu-Natal. 

PMID- 25866067
TI  - The impact of the HIV epidemic on the composite wellbeing of educators in South
      Africa: a qualitative study.
AB  - In South Africa, support is available for educators who are HIV-positive, and
      there are numerous initiatives to curb further HIV infections. What is lacking
      though is an understanding of how the HIV epidemic impacts on educators who are
      affected personally or professionally. For this reason a qualitative study was
      undertaken with 25 affected educators from the Gauteng and Free State provinces.
      Semi-structured interviews were conducted to determine how the epidemic is
      impacting the health of educators who are affected but not HIV infected. The
      results suggest that affected educators are in need of interventions that target
      health promotion, since those who participated reported poor physical, emotional,
      social, spiritual and professional health. The results also suggest that some
      educators do cope with the overall impact of the epidemic, implying that
      resilient functioning among affected educators should be promoted. 

PMID- 25866068
TI  - Neurological manifestations of HIV infection in Nigerians.
AB  - Nervous system complications commonly accompany HIV infection and are associated
      with significant morbidity and mortality. HIV incidence has been progressively
      increasing in Nigeria, yet the neurological manifestations of the disease have
      not been systematically studied in Nigerians. This study aimed to describe the
      nature and frequency of neurological manifestations associated with HIV infection
      in a sample of 202 Nigerians. This was a prospective study of patients with
      documented HIV infection who attended a referral centre clinic in Abuja in 2003.
      A personal history, general and neurological examinations, and other relevant
      medical investigations were carried out for all subjects. A mini mental-state
      exam was carried out with those willing to cooperate. In all, 89 patients (44%)
      were diagnosed with at least one neurological disorder. Herpes zoster and
      cognitive impairment were the most frequent, each present in 12.3% of the study
      group. Peripheral neuropathy and facial palsy were also present, in 10.4% and
      3.9% of subjects, respectively. Brain mass lesions, seizure disorder,
      cryptococcal meningitis, cord compression syndrome, and trigeminal neuralgia were
      also documented. There was no significant difference demographically between
      subjects with or without neurological impairment. Future studies in this area
      should utilise nerve conduction studies and more detailed testing of cognitive
      function to further characterise the neurological manifestations of HIV
      infection. 

PMID- 25866069
TI  - Misconceptions about HIV prevention and transmission in Botswana.
AB  - Misconceptions about how HIV can be transmitted or prevented often prevent
      individuals from making informed choices and taking appropriate action. The
      purpose of the research was to explore the socio-demographic and behavioural
      factors in Botswana that are associated with misconceptions about HIV prevention
      and transmission. The data used were from the Botswana AIDS Impact Survey II
      conducted in 2004, which constitutes a nationally representative sample. Results
      from bivariate and multivariate analyses show that young people, males, the less
      educated, those who did not use a condom during their last instance of sexual
      intercourse, and those who believe that nothing can be done to reduce HIV
      infection are most likely to harbour misconceptions about how HIV can be
      prevented and transmitted. Since misconceptions may prevent people from making
      informed choices, intervention programmes aimed at HIV prevention should aim to
      dispel misconceptions about HIV and AIDS as an important part of their strategy.
      Targeted HIV prevention and education programmes are needed in an effort to
      dispel such misconceptions and likewise to address the needs of different
      population sub-groups. 

PMID- 25866070
TI  - Comparative analysis of nursing and midwifery regulatory and professional bodies'
      scope of practice and associated decision-making frameworks: a discussion paper.
AB  - AIMS: To review, discuss and compare nursing and midwifery regulatory and
      professional bodies' scope of practice and associated decision-making frameworks.
      BACKGROUND: Scope of practice in professional nursing and midwifery is an
      evolving process which needs to be responsive to clinical, service, societal,
      demographic and fiscal changes. Codes and frameworks offer a system of rules and
      principles by which the nursing and midwifery professions are expected to
      regulate members and demonstrate responsibility to society. DESIGN: Discussion
      paper. DATA SOURCES: Twelve scope of practice and associated decision-making
      frameworks (January 2000-March 2014). IMPLICATIONS FOR NURSING: Two main
      approaches to the regulation of the scope of practice and associated decision
      making frameworks exist internationally. The first approach is policy and
      regulation driven and behaviour oriented. The second approach is based on notions
      of autonomous decision-making, professionalism and accountability. The two
      approaches are not mutually exclusive, but have similar elements with a different
      emphasis. Both approaches lack explicit recognition of the aesthetic aspects of
      care and patient choice, which is a fundamental principle of evidence-based
      practice. CONCLUSION: Nursing organizations, regulatory authorities and nurses
      should recognize that scope of practice and the associated responsibility for
      decision-making provides a very public statement about the status of nursing in a
      given jurisdiction.

PMID- 25866071
TI  - Waveform selectivity at the same frequency.
AB  - Electromagnetic properties depend on the composition of materials, i.e. either
      angstrom scales of molecules or, for metamaterials, subwavelength periodic
      structures. Each material behaves differently in accordance with the frequency of
      an incoming electromagnetic wave due to the frequency dispersion or the resonance
      of the periodic structures. This indicates that if the frequency is fixed, the
      material always responds in the same manner unless it has nonlinearity. However,
      such nonlinearity is controlled by the magnitude of the incoming wave or other
      bias. Therefore, it is difficult to distinguish different incoming waves at the
      same frequency. Here we present a new concept of circuit-based metasurfaces to
      selectively absorb or transmit specific types of waveforms even at the same
      frequency. The metasurfaces, integrated with schottky diodes as well as either
      capacitors or inductors, selectively absorb short or long pulses, respectively.
      The two types of circuit elements are then combined to absorb or transmit
      specific waveforms in between. This waveform selectivity gives us another degree
      of freedom to control electromagnetic waves in various fields including wireless
      communications, as our simulation reveals that the metasurfaces are capable of
      varying bit error rates in response to different waveforms. 

PMID- 25866072
TI  - Factors influencing high school coaches' adoption of injury prevention programs.
AB  - OBJECTIVES: Despite documented efficacy of injury prevention programs (IPPs) to
      reduce sport-related lower extremity injury risk, there is evidence of a lack of
      widespread IPP adoption by high school coaches. This study identified factors
      related to non-adoption of IPPs by assessing coaches' knowledge, attitudes, and
      behaviors related to prevention programs and comparing attitudes between adopter
      and non-adopter coaches. DESIGN: Cross-sectional. METHODS: Head soccer and
      basketball coaches (n=141) from 15 Oregon high schools were invited to complete a
      web-based survey assessing their IPP-related knowledge, attitudes, and behaviors.
      RESULTS: Of the 66 coach respondents, 52% reported being aware of IPPs; 21%
      reported using an IPP with their team; and 9% reported having their student
      athletes perform the IPP exactly as designed. No apparent differences in the
      attitudes toward the importance of injury prevention or the effectiveness of IPPs
      were identified between coaches that did and did not adopt an IPP. Perceptions
      that efficacious IPPs do not offer a relative advantage over coaches' existing
      practices, do not align with coaches' needs (compatibility), and are difficult to
      implement in their setting (complexity) emerged as key factors underlying
      coaches' decisions not to adopt a program. Of those that did report adopting an
      IPP, just 43% (6/14) reported implementing the program as designed. CONCLUSIONS:
      Improving preventative practices of high school coaches requires more than
      improved dissemination to increase coach awareness. To improve the rate of IPP
      adoption and implementation fidelity, coach education should directly address
      issues related to relative advantage, compatibility, and complexity.

PMID- 25866073
TI  - Genomic best linear unbiased prediction method reflecting the degree of linkage
      disequilibrium.
AB  - The degree of linkage disequilibrium (LD) between markers differs depending on
      the location of the genome; this difference biases genetic evaluation by genomic
      best linear unbiased prediction (GBLUP). To correct this bias, we used three
      GBLUP methods reflecting the degree of LD (GBLUP-LD). In the three GBLUP-LD
      methods, genomic relationship matrices were conducted from single nucleotide
      polymorphism markers weighted according to local LD levels. The predictive
      abilities of GBLUP-LD were investigated by estimating variance components and
      assessing the accuracies of estimated breeding values using simulation data. When
      quantitative trait loci (QTL) were located at weak LD regions, the predictive
      abilities of the three GBLUP-LD methods were superior to those of GBLUP and
      Bayesian lasso except when the number of QTL was small. In particular, the
      superiority of GBLUP-LD increased with decreasing trait heritability. The rates
      of QTL at weak LD regions would increase when selection by GBLUP continues; this
      consequently decreases the predictive ability of GBLUP. Thus, the GBLUP-LD could
      be applicable for populations selected by GBLUP for a long time. However, if QTL
      were located at strong LD regions, the accuracies of three GBLUP-LD methods were
      lower than GBLUP and Bayesian lasso. 

PMID- 25866074
TI  - FRET-based screening assay using small-molecule photoluminescent probes in lysate
      of cells overexpressing RFP-fused protein kinases.
AB  - An assay was developed for the characterization of protein kinase inhibitors in
      lysates of mammalian cells based on the measurement of FRET between overexpressed
      red fluorescent protein (TagRFP)-fused protein kinases (PKs) and luminophore
      labeled small-molecule inhibitors (ARC-Photo probes). Two types of the assay, one
      using TagRFP as the photoluminescence donor together with ARC-Photo probes
      containing a red fluorophore dye as acceptor, and the other using TagRFP as the
      acceptor fluorophore in combination with a terbium cryptate-based long-lifetime
      photoluminescence donor, were used for FRET-based measurements in lysates of the
      cells overexpressing TagRFP-fused PKs. The second variant of the assay enabled
      the performance of the measurements under time-resolved conditions that led to
      substantially higher values of the signal/background ratio and further improved
      the reliability of the assay. 

PMID- 25866075
TI  - Kinetic investigation of recombinant human hyaluronidase PH20 on hyaluronic acid.
AB  - The kinetic investigation of hyaluronidases using physiologically relevant
      hyaluronic acid (HA or hyaluronan) substrate will provide useful and important
      clues to their catalytic behavior and function in vivo. We present here a simple
      and sensitive method for kinetic measurement of recombinant human hyaluronidase
      PH20 (rHuPH20) on HA substrates with sizes ranging from 90 to 752 kDa. The method
      is based on 2-aminobenzamide labeling of hydrolyzed HA products combined with
      separation by size exclusion-ultra performance liquid chromatography coupled with
      fluorescence detection. rHuPH20 was found to follow Michaelis-Menten kinetics
      during the initial reaction time. Optimal reaction rates were observed in the pH
      range of 4.5-5.5. The HA substrate size did not have significant effects on the
      initial rate of the reaction. By studying HA substrates of 215, 357, and 752 kDa,
      the kinetic parameters Km, Vmax, and kcat were determined to be 0.87-0.91 mg/ml,
      1.66-1.74 NM s(-1), and 40.5-42.4 s(-1), respectively. This method allows for
      direct measurement of kinetics using physiologically relevant HA substrates and
      can be applied to other hyaluronidase kinetic measurements.

PMID- 25866076
TI  - High-throughput screening-compatible assays of As(III) S-adenosylmethionine
      methyltransferase activity.
AB  - Arsenic is a naturally existing toxin and carcinogen. As(III) S
      adenosylmethionine methyltransferases (AS3MT in mammals and ArsM in microbes)
      methylate As(III) three times in consecutive steps and play a central role in
      arsenic metabolism from bacteria to humans. Current assays for arsenic
      methylation are slow, laborious, and expensive. Here we report the development of
      two in vitro assays for AS3MT activity that are rapid, sensitive, convenient, and
      relatively inexpensive and can be adapted for high-throughput assays. The first
      assay measures As(III) binding by the quenching of the protein fluorescence of a
      single-tryptophan derivative of an AS3MT ortholog. The second assay utilizes time
      resolved fluorescence resonance energy transfer to directly measure the
      conversion of the AS3MT substrate, S-adenosylmethionine, to S
      adenosylhomocysteine catalyzed by AS3MT. These two assays are complementary, one
      measuring substrate binding and the other catalysis, making them useful tools for
      functional studies and future development of drugs to prevent arsenic-related
      diseases. 

PMID- 25866078
TI  - Ultra-sensitive flow measurement in individual nanopores through pressure--driven
      particle translocation.
AB  - A challenge for the development of nanofluidics is to develop new instrumentation
      tools, able to probe the extremely small mass transport across individual
      nanochannels. Such tools are a prerequisite for the fundamental exploration of
      the breakdown of continuum transport in nanometric confinement. In this letter,
      we propose a novel method for the measurement of the hydrodynamic permeability of
      nanometric pores, by diverting the classical technique of Coulter counting to
      characterize a pressure-driven flow across an individual nanopore. Both the
      analysis of the translocation rate, as well as the detailed statistics of the
      dwell time of nanoparticles flowing across a single nanopore, allow us to
      evaluate the permeability of the system. We reach a sensitivity for the water
      flow down to a few femtoliters per second, which is more than two orders of
      magnitude better than state-of-the-art alternative methods. 

PMID- 25866077
TI  - Polysialic acid as an antigen for monoclonal antibody HIgM12 to treat multiple
      sclerosis and other neurodegenerative disorders.
AB  - CNS regeneration is a desirable goal for diseases of brain and spinal cord.
      Current therapeutic strategies for the treatment of multiple sclerosis (MS) aim
      to eliminate detrimental effects of the immune system, so far without reversing
      disability or affecting long-term prognosis in patients. Approachable molecular
      targets that stimulate CNS repair are not part of the clinical praxis or have not
      been identified yet. The purpose of this study was to identify the molecular
      target of the human monoclonal antibody HIgM12. HIgM12 reverses motor deficits in
      chronically demyelinated mice, a model of MS. Here, we identified polysialic acid
      (PSA) attached to the neural cell adhesion molecule (NCAM) as the antigen for
      HIgM12 by using different NCAM knockout strains and through PSA removal from the
      NCAM protein core. Antibody binding to CNS tissue and primary cells, antibody
      mediated cell adhesion, and neurite outgrowth on HIgM12-coated nitrocellulose was
      detected only in the presence of PSA as assessed by western blotting,
      immunoprecipitation, immunocytochemistry, and histochemistry. We conclude that
      HIgM12 mediates its in vivo and in vitro effects through binding to PSA and has
      the potential to be an effective therapy for MS and neurodegenerative diseases.
      The human antibody HIgM12 stimulates neurite outgrowth in vitro and promotes
      function in chronically demyelinated mice, a model of multiple sclerosis. The
      cellular antigen for HIgM12 was undetermined. Here, we identified polysialic acid
      attached to NCAM (neural cell adhesion molecule) as the cellular target for
      HIgM12. This includes glial fibrillary acidic protein (GFAP)-positive mouse
      astrocytes (GFAP, red; HIgM12, green; DAPI, blue) among other cell types of the
      central nervous system. These findings indicate a new strategy for the treatment
      of neuro-motor disorders including multiple sclerosis.

PMID- 25866079
TI  - The hydroxytyrosol-dependent increase of TNF-alpha in LPS-activated human
      monocytes is mediated by PGE2 and adenylate cyclase activation.
AB  - An accurate regulation of PGE2 and TNF-alpha production is an important event for
      a physiological inflammation process. We have recently reported that in LPS
      activated human monocytes hydroxytyrosol, the main phenol present in extra virgin
      olive oil reduced both the COX-2 gene expression and PGE2 secretion while it
      increased the TNF-alpha accumulation in the culture medium. Here we have
      investigated whether these effects were related to each other, clarifying the
      possible mechanisms involved. We found that hydroxytyrosol (100 MUM) increased
      the TNF-alpha mRNA level in LPS-activated human monocytes as evaluated by both RT
      PCR and real time PCR (qPCR). Exogenous PGE2 reduced both TNF-alpha mRNA and TNF
      alpha secretion (EIA assay) while the activation of adenylate cyclase by
      forskolin decreased only the TNF-alpha secretion but did not influence the TNF
      alpha mRNA level. Acting similarly to non steroidal anti-inflammatory drugs
      (NSAIDs), the hydroxytyrosol could be used to develop innovative drugs for the
      control of inflammation and immune response. The decrease of TNF mediated by
      forskolin, moreover, could suggest that the pharmacological regulation of cAMP
      production may represent a strategy to control the side effects of NSAIDs.

PMID- 25866080
TI  - Effect of crop management and sample year on abundance of soil bacterial
      communities in organic and conventional cropping systems.
AB  - AIMS: To identify changes in the bacterial community, at the phylum level brought
      about by varied crop management. METHODS AND RESULTS: Next-generation sequencing
      methods were used to compare the taxonomic structure of the bacterial community
      within 24 agricultural soils managed with either organic or conventional methods,
      over a 3-year period. Relative abundance of the proportionately larger phyla
      (e.g. Acidobacteria and Actinobacteria) was primarily affected by sample year
      rather than crop management. Changes of abundance in these phyla were correlated
      with changes in pH, organic nitrogen and soil basal respiration. Crop management
      affected some of the less dominant phyla (Chloroflexi, Nitrospirae,
      Gemmatimonadetes) which also correlated with pH and organic N. CONCLUSION: Soil
      diversity can vary with changing environmental variables and soil chemistry. If
      these factors remain constant, soil diversity can also remain constant even under
      changing land use. SIGNIFICANCE AND IMPACT OF THE STUDY: The impact of crop
      management on environmental variables must be considered when interpreting
      bacterial diversity studies in agricultural soils. Impact of land use change
      should always be monitored across different sampling time points. Further studies
      at the functional group level are necessary to assess whether management-induced
      changes in bacterial community structure are of biological and agronomic
      relevance.

PMID- 25866081
TI  - Research Review: Neuropsychological test performance in pediatric obsessive
      compulsive disorder--a meta-analysis.
AB  - BACKGROUND: Research into the neuropsychology of pediatric obsessive-compulsive
      disorder (OCD) reveals inconsistent results, limiting the ability to draw
      conclusions about possible neurocognitive deficits in youth with OCD. The aim of
      this study was to conduct a meta-analysis of the available literature. METHODS:
      We identified 36 studies, of which 11 studies met inclusion criteria. Results
      were categorized into nine functional subdomains: planning, response
      inhibition/interference control, set shifting/cognitive flexibility, verbal
      memory, nonverbal memory, processing speed, working memory, visuospatial
      functions, and attention. For each domain, weighted pooled Hedges' g effect size
      was calculated using random model analyses. RESULTS: Small effect sizes were
      found across all subdomains, none of which were found to be statistically
      significant. DISCUSSION: Results indicate that youth with OCD do not exhibit
      noteworthy neuropsychological deficits. This is in line with recent suggestions
      that OCD may not be characterized by clinically meaningful neuropsychological
      impairments. However, the small number of available controlled studies highlights
      the urgent need for more neuropsychological research in this population, as well
      as for further exploration of the neurodevelopmental hypothesis in pediatric OCD.
      Finally, the relatively low persistence rates of OCD into adulthood should be
      taken under consideration, especially in the context of the putative
      neuropsychological performance differences between adult and pediatric OCD
      populations.

PMID- 25866082
TI  - Organocatalytic diastereoselective synthesis of chiral decalines through the
      domino Claisen-Schmidt/Henry reaction.
AB  - General and operative domino Claisen-Schmidt/Henry (CS/H) reaction has been
      revealed to obtain highly substituted chiral decalines in good yields with
      excellent ees and des by using push-pull enamine catalysis. 

PMID- 25866083
TI  - An integrative taxonomic investigation of the diversity of digenean parasites
      infecting the intertidal snail Austrolittorina unifasciata Gray, 1826
      (Gastropoda: Littorinidae) in Australia.
AB  - We investigated for the first time the digenean parasites of Austrolittorina
      unifasciata Gray (Gastropoda: Littorinidae), a periwinkle snail inhabiting the
      rocky shores of Australia. Here we present detailed morphological descriptions
      and molecular data (sequences for the mitochondrial cox1 and the nuclear 28S rRNA
      gene) for the cercariae and intramolluscan stages of the digenean parasites
      found. Five species, one each of the families Notocotylidae Luhe, 1909,
      Gorgocephalidae Manter, 1966 and Philophthalmidae Looss, 1899, and two of the
      family Renicolidae Dollfus, 1939, were recorded and characterised molecularly.
      Phylogenetic analyses at the superfamily level provided evidence for the familial
      and generic affiliation of the species and their relationships with congeners.
      This study is the first to provide data on the life cycle of a species of the
      family Gorgocephalidae, a parasite of kyphosid fish for which only adult stages
      had, thus far, been described. The relatively high prevalence of this species
      allowed mapping of the cox1 haplotype distribution of Gorgocephalus sp. Aus along
      the southern coast of New South Wales. 

PMID- 25866087
TI  - Ultra high performance liquid chromatography with electrospray ionization tandem
      mass spectrometry coupled with hierarchical cluster analysis to evaluate
      Wikstroemia indica (L.) C. A. Mey. from different geographical regions.
AB  - A sensitive, rapid and simple ultra high performance liquid chromatography with
      electrospray ionization tandem mass spectrometry method was developed to
      determine seven constituents (umbelliferone, apigenin, triumbelletin,
      daphnoretin, arctigenin, genkwanin and emodin) in Wikstroemia indica (L.) C. A.
      Mey. The chromatographic analysis was performed on an ACQUITY UPLC(r) BEH C18
      column (2.1 * 50 mm, 1.7 MUm) by gradient elution with the mobile phase of 0.05%
      formic acid aqueous solution (A) and acetonitrile (B). Multiple reaction
      monitoring mode with positive and negative electrospray ionization interface was
      carried out to detect the components. This method was validated in terms of
      specificity, linearity, accuracy, precision and stability. Excellent linear
      behavior was observed over the certain concentration ranges with the correlation
      coefficient values higher than 0.999. The intraday and innerday precisions were
      within 2.0%. The recoveries of seven analytes were 99.4-101.1% with relative
      standard deviation less than 1.2%. The 18 Wikstroemia indica samples from
      different origins were classified by hierarchical clustering analysis according
      to the contents of seven components. The results demonstrated that the developed
      method could successfully be used to quantify simultaneously of seven components
      in Wikstroemia indica and could be a helpful tool for the detection and
      confirmation of the quality of traditional Chinese medicines. 

PMID- 25866089
TI  - Reform of federation: An opportunity for rural health.

PMID- 25866090
TI  - Not just a fisherman's wife: Women's contribution to health and wellbeing in
      commercial fishing.
AB  - OBJECTIVE: To explore the role of women in fishing industry organisations and
      communities in promoting best-practice health behaviours among fishers in
      Australia. DESIGN: This paper reports aspects of research that examined how the
      fishing industry can best support physical health and mental well-being of
      fishers. The study employed a mixed-methods, multisite case study approach. Data
      were gathered from face-to-face and phone interactions. SETTING: Two sites in
      Victoria and one in Western Australia. PARTICIPANTS: Thirty-one male fishers,
      including commercial licence owners, skippers, deckhands, three female family
      members, three fishing association representatives, one local government
      representative, two health care providers, and three regional health planning and
      funding bodies. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Not
      applicable. RESULTS: Often unrecognised, women associated with the fishing
      industry are integral to the promotion of good health for fishers. They are key
      to identifying health issues (particularly mental health issues) and proposing
      community-based health and well-being strategies. They often do so by
      incorporating health information and activities into 'soft entry points' -
      informal, non-health service mechanisms by which fishers can access health
      information and health services. CONCLUSIONS: While not working at the industry
      coalface, women have a stake, and are key players, in the commercial fishing
      industry. Their knowledge of, and credibility within, fishing enterprises makes
      them valuable sources of information about health issues facing the industry and
      effective strategies to address them. This expertise should be applied in
      conjunction with industry associations and health providers to achieve better
      health outcomes for fishers and their families.

PMID- 25866091
TI  - Farmers' work-day noise exposure.
AB  - OBJECTIVE: This study aims to understand the extent of farmers' exposure to
      hazardous noise, and trial and test the ability of an on-farm noise audit report
      to improve awareness and preventative action towards farm based noise hazards.
      DESIGN: Visits were made to working farms where noise and dosimetry measurements
      undertaken. During return visits, the noise measurements were explained in a
      brief report. A follow-up questionnaire was implemented gathering feedback on the
      use or otherwise of the report. SETTING: Working farms in Western Victoria and SE
      Queensland including dairy, beef, wool, prime lamb and cropping. PARTICIPANTS:
      Participants were 14 female and 37 male farm workers. INTERVENTIONS: Noise
      exposure assessment of daily activities through dosimetry; measurements of noisy
      tasks and machinery; supply and interpretation of a noise audit report. MAIN
      OUTCOME MEASURES: Participants were supplied with a 'noise report' of their
      workplace together with an explanation of the report's meaning to farm workers.
      RESULTS: Men and women have similar at risk exposures. The average noise exposure
      was 1.09 Pa(2)h (LAeq,8h  = 85.3 dB). This implies 163 000 Australian
      agricultural workers are at risk from hazardous noise. On-farm noise audit
      reports were a relevant and valuable feedback to farmers in relation to their
      potential noise hazards. CONCLUSIONS: Of those measured 51%, and by extrapolation
      163 000 Australian agricultural workers, have noise exposure levels greater than
      the recommended Australian Standard of 1.01 Pa(2)h (85 dB). Men and women are
      equally exposed. On-farm noise audit reports are an effective feedback to
      increase awareness and improve hearing health.

PMID- 25866092
TI  - Impact of support group intervention on family system strengths of rural
      caregivers of stroke patients in India.
AB  - OBJECTIVE: The objective of this study is to evaluate the impact of support group
      intervention on family system strengths of rural caregivers of stroke patients.
      DESIGN: True experimental pretest and post-test design was adopted for the study.
      SETTING: The study was conducted in Kattankulathur Block, a rural area in
      Kancheepuram district, India. PARTICIPANTS: Two hundred forty caregivers of
      stroke patients were selected by simple random sampling technique. INTERVENTION:
      Enrolment in self-help groups and attending meetings were used as the
      interventional strategy for the purpose of this study. MAIN OUTCOME MEASURE: The
      main outcome of the study was to evaluate the impact of support group
      intervention on family system strengths of rural caregivers of stroke patients.
      RESULTS: Following intervention, the mean score and the standard deviation of the
      experimental group increased to 44.73 and 5.83, respectively, the control group
      mean score remained at 22.08 and the standard deviation was 3.07 at t = 37.58. P
      value was 0.001, which is statistically significant at the confidence interval of
      39.45%. CONCLUSION: It was found that there was a significant and positive
      increase in the family system strengths of caregivers who participated in the
      self-help group meetings, thereby suggesting that support group intervention
      programs are an effective nursing strategy that can be employed for improving the
      overall well-being of the caregivers of stroke patients.

PMID- 25866093
TI  - Darwin conference: Remote health check.

PMID- 25866088
TI  - Longevity and skeletal muscle mass: the role of IGF signalling, the sirtuins,
      dietary restriction and protein intake.
AB  - Advancing age is associated with a progressive loss of skeletal muscle (SkM) mass
      and function. Given the worldwide aging demographics, this is a major contributor
      to morbidity, escalating socio-economic costs and ultimately mortality.
      Previously, it has been established that a decrease in regenerative capacity in
      addition to SkM loss with age coincides with suppression of insulin/insulin-like
      growth factor signalling pathways. However, genetic or pharmacological
      modulations of these highly conserved pathways have been observed to
      significantly enhance life and healthspan in various species, including mammals.
      This therefore provides a controversial paradigm in which reduced regenerative
      capacity of skeletal muscle tissue with age potentially promotes longevity of the
      organism. This paradox will be assessed and considered in the light of the
      following: (i) the genetic knockout, overexpression and pharmacological models
      that induce lifespan extension (e.g. IRS-1/s6K KO, mTOR inhibition) versus the
      important role of these signalling pathways in SkM growth and adaptation; (ii)
      the role of the sirtuins (SIRTs) in longevity versus their emerging role in SkM
      regeneration and survival under catabolic stress; (iii) the role of dietary
      restriction and its impact on longevity versus skeletal muscle mass regulation;
      (iv) the crosstalk between cellular energy metabolism (AMPK/TSC2/SIRT1) and
      survival (FOXO) versus growth and repair of SkM (e.g. AMPK vs. mTOR); and (v) the
      impact of protein feeding in combination with dietary restriction will be
      discussed as a potential intervention to maintain SkM mass while increasing
      longevity and enabling healthy aging. 

PMID- 25866094
TI  - Optimal husbandry of hatchling Eastern Indigo Snakes (Drymarchon couperi) during
      a captive head-start program.
AB  - Optimal husbandry techniques are desirable for any headstart program, but
      frequently are unknown for rare species. Here we describe key reproductive
      variables and determine optimal incubation temperature and diet diversity for
      Eastern Indigo Snakes (Drymarchon couperi) grown in laboratory settings. Optimal
      incubation temperature was estimated from two variables dependent on temperature,
      shell dimpling, a surrogate for death from fungal infection, and deviation of an
      egg from an ovoid shape, a surrogate for death from developmental anomalies.
      Based on these relationships and size at hatching we determined optimal
      incubation temperature to be 26 degrees C. Additionally, we used incubation data
      to assess the effect of temperature on duration of incubation and size of
      hatchlings. We also examined hatchling diets necessary to achieve optimal growth
      over a 21-month period. These snakes exhibited a positive linear relationship
      between total mass eaten and growth rate, when individuals were fed less than
      1711 g of prey, and displayed constant growth for individuals exceeding 1711 g of
      prey. Similarly, growth rate increased linearly with increasing diet diversity up
      to a moderately diverse diet, followed by constant growth for higher levels of
      diet diversity. Of the two components of diet diversity, diet evenness played a
      stronger role than diet richness in explaining variance in hatchling growth.
      These patterns document that our goal of satiating snakes was achieved for some
      individuals but not others and that diets in which total grams consumed over the
      first 21 months of life is distributed equivalently among at least three prey
      genera yielded the fastest growth rates for hatchling snakes.

PMID- 25866095
TI  - Carboxylic-Acid-passivated metal oxide nanocrystals: ligand exchange
      characteristics of a new binding motif.
AB  - Ligand exchange is central in the processing of inorganic nanocrystals (NCs) and
      requires understanding of surface chemistry. Studying sterically stabilized HfO2
      and ZrO2 NCs using (1) H solution NMR and IR spectroscopy as well as elemental
      analysis, this paper demonstrates the reversible exchange of initial oleic acid
      ligands for octylamine and self-adsorption of oleic acid at NC surfaces. Both
      processes are incompatible with an X-type binding motif of carboxylic acids as
      reported for sulfide and selenide NCs. We argue that this behavior stems from the
      dissociative adsorption of carboxylic acids at the oxide surface. Both proton and
      carboxylate moieties must be regarded as X-type ligands yielding a combined X2
      binding motif that allows for self-adsorption and exchange for L-type ligands. 

PMID- 25866096
TI  - R-CHOP therapy alone for limited-stage follicular lymphoma.
AB  - Irradiation therapy alone is a standard strategy for limited-stage FL, leading to
      a 10-year progression-free survival (PFS) rate of 30-50%. However, we have been
      administering R-CHOP therapy alone to patients with limited-stage FL. A total of
      35 patients with newly diagnosed FL received R-CHOP therapy with curative intent
      between 2002 and 2009. The median age of the 35 patients was 61 years; 7 patients
      had in CS 1 FL, and 28 patients, CS 2 FL. The median number of R-CHOP cycles was
      6. On completion of the R-CHOP therapy, 33 patients achieved complete response
      and 1 showed partial response (PR). The patient showing PR after the completion
      of R-CHOP was administered additional irradiation. The remaining 1 patient was
      not evaluated because of discontinuation of hospital visit. In all the 35
      patients, the 5-year PFS rate was 70%, and the 5-year overall survival rate was
      92%. In the 15 patients with a PFS>5 years, only 1 patient showed disease
      progression. The outcome of R-CHOP therapy alone in patients with limited-stage
      FL was at least equivalent to the reported outcome of irradiation therapy alone.
      R-CHOP therapy could be an alternative to irradiation therapy in limited-stage FL
      patients. 

PMID- 25866097
TI  - MicroRNA signature is indicative of long term prognosis in diffuse large B-cell
      lymphoma.
AB  - PURPOSE: To compare microRNA (miR) expression between patients with diffuse large
      B-cell lymphoma (DLBCL) who had a poor prognosis to those who had a favorable
      prognosis. METHODS: The study group included 83 patients with diffuse large B
      cell lymphoma (DLBCL) treated between the years 1995 and 2003 without rituximab
      in a single tertiary center for whom adequate tumor content was available. miR
      signature from tissue biopsies was compared between patients who relapsed within
      nine months from commencement of treatment (defined as poor prognosis, n=43) and
      those with disease-free survival of at least five years (defined as good
      prognosis, n=40). RNA was analyzed using custom microarrays. Quantitative real
      time polymerase chain reaction (qRT-PCR) was used for technical validation of
      microarray results. An independent set of 13 samples was used for further
      validation. RESULTS: Eight miRs were found to be differently expressed between
      the two prognostic groups. The expression of the different miRs was verified by
      qRT-PCR, showing high correlation with the microarray data in both verification
      and independent set groups. No added value to the clinically based International
      Prognostic Index was found. CONCLUSION: miR signature from DLBCL biopsies can
      discriminate between patients with favorable and poor prognoses.

PMID- 25866098
TI  - Changes of the glycemic control and therapeutic regimen for diabetes mellitus in
      the Japanese patients on hemodialysis.
AB  - OBJECTIVES/METHODS: Diabetes mellitus (DM) has become important with regard to
      mortality in hemodialysis (HD) patients, so it is necessary to optimize the
      treatment of these patients. We examined the changes in glycemic control and
      therapeutic regimen, including insulin and oral hypoglycemic agent (OHA) and the
      diet/exercise in the HD patients. RESULTS: Although DM was observed in 42 (32.6%)
      of the 129 (male/female 89/40) patients, there was a male predominance, with 35
      DM patients being male (83.3%). The therapeutic regimens of DM patients were as
      follows: insulin was used in 13, OHA in 20, and diet/exercise in nine patients.
      The DM patients, who had not used insulin, included five patients receiving OHA
      (25.0%) and diet/exercise in five patients (55.6%). Nineteen of 20 OHA patients
      used a dipeptidyl peptidase-IV inhibitor. Although the postprandial blood glucose
      (PBG) in insulin was 191 +/- 89 (the mean +/- standard deviation [SD]) mg/dL,
      that in OHA group was 140 +/- 36 mg/dL. The mean and the SD of the PBG were
      larger in insulin than in OHA group. The body mass index (BMI) and hemoglobin A1c
      were higher in patients treated with insulin (24.1 +/- 4.2 kg/m(2), 7.1 +/- 1.2%)
      than in patients treated with the OHA (21.2 +/- 2.8 kg/m(2), 5.8 +/- 0.5%;
      P<0.05) or diet/exercise (19.2 +/- 3.6 kg/m(2), 5.3 +/- 0.6%; P<0.05). The BMI
      and hemoglobin A1c were higher in diet/exercise compared to OHA and insulin
      groups. CONCLUSION: The patients undergoing HD develop DM, especially males. The
      BMI and hemoglobin A1c were useful to determine whether there should be a change
      from insulin to OHA or to diet/exercise therapy. A dipeptidyl peptidase-IV
      inhibitor might be a preferable treatment for the DM patients with HD in terms of
      the mean and SD of PBG.

PMID- 25866099
TI  - [The past and present of thumb reconstruction].
AB  - The thumb is the most important digit for hand function. Its role is not only
      functional, but also aesthetic, the hand being a very exposed part of the body.
      Loss of the thumb can lead to life-long physical and mental stigma. With regard
      to this experience, early reconstruction of the thumb in order to return patients
      to normal life as soon as possible is clearly preferred. When using early thumb
      reconstruction, the patient does not gain wrong stereotypes in hand-grip
      manoeuvres. The paper presents an overview of current options for non
      microsurgical and microsurgical thumb reconstruction techniques.

PMID- 25866100
TI  - [The ONSTEP inguinal hernia repair technique].
AB  - The ONSTEP (Open New Simplified Totally Extraperitoneal) inguinal/femoral hernia
      repair technique is an innovative procedure presented by Portuguese surgeons
      Augusto Lourenco and Rui Soares da Costa within the EHS/AHS Congress in March
      2012. The first institutions to perform this kind of hernia surgery in the Czech
      Republic are the Department of Surgery at Prostejov Hospital and the Department
      of Surgery at Frydlant Hospital. The ONSTEP technique represents a minimally
      traumatizing frontal approach to inguinal hernia repair using a special self
      expanding mesh patch (an oval, anatomically-shaped moderate-pore polypropylene
      mesh with the circumferential memory-ring consisting of polyethylene
      terephthalate). The main advantages of this method are: short duration of
      surgery, the possibility of performing the procedure under local anaesthesia,
      short recovery time and rapid return to daily activities, low incidence of
      chronic post-operative groin pain, low recurrence rate, short hospital stay, good
      cosmetic effect and a low price. It is suitable for institutions performing
      outpatient surgery.

PMID- 25866101
TI  - [Intraoperative sentinel lymph node detection in colon cancer resection -
      preliminary results].
AB  - INTRODUCTION: The aim of this paper is to evaluate the results of intraoperative
      sentinel node detection in colon cancer patients and to compare the number of
      nodes retrieved per specimen in comparison with standard resection. METHODS:
      Patients undergoing elective colon cancer resection were included in the study.
      The specimen and the sentinel lymph node were sent for histopathological
      examination. A group of patients from 2011 who underwent elective resection
      served as the study control. RESULTS: The control group comprised 56 patients.
      The average node count was 12.73 (4-27). The study group included 102 patients;
      29 patients had to be excluded because of protocol deviation. Out of the
      remaining 73 (46 male and 27 female) patients, 24 were N-positive and 2 of them
      were pN1c. In the remaining 22 patients, the sentinel node was positive in 8
      cases, corresponding to a sensitivity of 36.36%. The average lymph node count was
      15.97(3-30) after patent blue dye injection. CONCLUSION: Intraoperative sentinel
      lymph node detection is an easy and feasible method. Despite the low sensitivity,
      the main positive effect of the method is the increased lymph node count per
      resection specimen.

PMID- 25866102
TI  - [Acute necrotizing pancreatitis: traditional laparotomy vs. minimally invasive
      procedures].
AB  - INTRODUCTION: Treatment of necrotizing pancreatitis continues to evolve. The
      standard therapeutic method for infected pancreatic necrosis and its subsequent
      septic complications is open surgical drainage. The advances in radiological
      imaging and interventional radiology have enabled the development of minimally
      invasive procedures, i.e. percutaneous drainage (PCD) under CT/USG control,
      endoscopic transgastric necrosectomy (ENE), laparoscopic transperitoneal
      necrosectomy (LNE) and retroperitoneal access to pancreatic necrosis (RENE).
      METHODS: Patients with acute pancreatitis treated from 2002 to 2013 (n=932) were
      included in the study. In patients with a severe form of the disease, results
      obtained in two groups of patients were compared: the first group was treated by
      classic laparotomy (group A), the second one was treated by means of minimally
      invasive procedures (group B). Statistical analysis employed the chi-square test.
      RESULTS: During the mentioned period, 677 (72.6%) patients with a mild form and
      255 (27.4%) with a severe form of the disease were treated. The male/female ratio
      was 1.4:1. In the group of patients suffering from a severe form of acute
      pancreatitis, 171 patients were treated conservatively, mortality rate being at
      16.4% (28/171). Surgery was indicated in a total of 84 patients, mortality rate
      reaching 26.2% (22/84). Fifty-two of the patients underwent laparotomy (group A),
      minimally invasive procedures were used in a total of 32 patients (group B).
      Overall mortality in group A was 30.8% (16/52) vs. 18.8% (6/32) in group B, p =
      0.224. The average length of hospitalization was longer in group A (65.4 days;
      median 52.4 vs. 49 days; median 36.5 in group B). PCD was the most frequent
      procedure performed in 19 patients; 5 of them died due to ongoing sepsis and
      multiorgan failure and 2 of them underwent revisional laparotomy. RENE was
      performed in 8 patients; lumbotomy was used in 5 of them. ENE was performed on 2
      patients, 1 of them died, and LNE was used once. A less invasive procedure, the
      linea alba fasciotomy, was performed in 2 patients with intra-abdominal
      hypertension. CONCLUSION: Open surgical drainage represents the standard
      treatment for infected pancreatic necrosis. Minimally invasive procedures are
      suitable alternatives especially in critically ill patients providing lower
      morbidity and mortality rates.

PMID- 25866103
TI  - [Malignant mesothelioma in the peritoneal cavity - a case report].
AB  - Malignant mesothelioma is a rare tumour with an incidence of 0.53 cases per
      million inhabitants. Only about 20% of cases occur in the peritoneum. The authors
      use the case report of a male patient with malignant mesothelioma occurring in
      the peritoneal cavity to demonstrate the difficulty of preoperative diagnosis:
      preoperative examinations made the authors consider a primary liver tumour and
      only definitive histological examination revealed the diagnosis. The discussion
      deals with the epidemiology, diagnosis and treatment of this rare disease and
      underlines the unique role of surgical therapy in its management.

PMID- 25866104
TI  - [Sigmoid colon cancer in pregnancy - a case report].
AB  - Colorectal cancer in pregnancy is a rare but life-threatening disease. The
      authors present a case of early-stage sigmoid colon cancer in pregnancy,
      discussing the issue in the light of the current literature.

PMID- 25866105
TI  - [Massive small intestine bleeding: CT-angiography and surgical treatment - a case
      report].
AB  - Gastrointestinal bleeding is one of acute abdomen conditions that occur
      relatively frequently. Most cases can nowadays be managed endoscopically, surgery
      is rarely required. Approximately 5% of gastrointestinal bleeding cases are cases
      of so-called obscure gastrointestinal bleeding. The presented massive
      gastrointestinal bleed case report provides a current view on diagnostic and
      therapeutic modalities in the context of everyday clinical practice.

PMID- 25866106
TI  - Development of a Multiplex Real-Time PCR Assay for the Detection of Treponema
      pallidum, HCV, HIV-1, and HBV.
AB  - Treponema pallidum, hepatitis C virus (HCV), human immunodeficiency virus (HIV)
      1, and hepatitis B virus (HBV) are major causes of sexually transmitted diseases
      passed through blood contact. The development of a sensitive and efficient method
      for detection is critical for early diagnosis and for large-scale screening of
      blood specimens in China. This study aims to establish an assay to detect these
      pathogens in clinical serum specimens. We established a TaqMan-locked nucleic
      acid (LNA) real-time polymerase chain reaction (PCR) assay for rapid, sensitive,
      specific, quantitative, and simultaneous detection and identification. The copy
      numbers of standards of these 4 pathogens were quantified. Standard curves were
      generated by determining the mean cycle threshold values versus 10-fold serial
      dilutions of standards over a range of 10(6) to 10(1) copies/MUL, with the lowest
      detection limit of the assay being 10(1) copies/MUL. The assay was applied to 328
      clinical specimens and compared with enzyme-linked immunosorbent assay (ELISA)
      and commercial nucleic acid testing (NAT) methods. The assay identified 39 T.
      pallidum-, 96 HCV-, 13 HIV-1-, 123 HBV-, 5 HBV/HCV-, 1 T. pallidum/HBV-, 1 HIV
      1/HCV-, and 1 HIV-1/T. pallidum-positive specimens. The high sensitivity of the
      assay confers strong potential for its use as a highly reliable, cost-effective,
      and useful molecular diagnostic tool for large-scale screening of clinical
      specimens. This assay will assist in the study of the pathogenesis and
      epidemiology of sexually transmitted blood diseases. 

PMID- 25866107
TI  - Dynamic Constitution of the Pathogens Inducing Encephalitis in Hand, Foot and
      Mouth Disease in Kunming, 2009-2011.
AB  - Hand, foot and mouth disease (HFMD), caused by various viral pathogens, is an
      emerging infectious disease in children in Asia. Understanding the composition of
      these pathogens is necessary to prevent and control this disease. In the present
      study, the pathogens in 436 HFMD patients (from 2009 to 2011) with concurrent
      clinical indications of encephalitis, meningoencephalitis, or both, were defined
      using the semi-nested PCR. A systematic analysis of the composition of these
      pathogens was performed. Various enteroviruses that are capable of inducing
      central nervous system (CNS) damage in HFMD patients were identified, including
      enterovirus 71, coxsackievirus A16, and Echovirus 9. Most of these pathogens were
      found co-infecting the patients. The composition of the pathogens that induced
      CNS damage in the HFMD patients was dynamically modulated in the cases. 

PMID- 25866108
TI  - Procalcitonin Level and Its Predictive Effect on Mortality in Crimean-Congo
      Hemorrhagic Fever Patients.
AB  - Crimean-Congo hemorrhagic fever (CCHF) is a potentially fatal disease which is
      endemic to Turkey. We aimed to investigate the procalcitonin levels and their
      prognostic value over fatality in CCHF patients. The sera were harvested from
      patients who were diagnosed with CCHF within the first 2 days of the onset of
      their symptoms. The patients were divided into 2 groups according to their
      survival status: fatal or non-fatal. The biochemical and hematological parameters
      were studied in the Biochemistry Laboratory of Sorgun City Hospital. The sera
      were stored at -80C until testing for procalcitonin, and the procalcitonin levels
      were assayed by ELISA at the Biochemistry Laboratory of Kirikkale University.
      Forty- eight patients were included in the study, with 8 and 40 patients in the
      fatal and non-fatal groups, respectively. While the procalcitonin level was high
      in all patients in the fatal group, the same was observed in 30 patients in the
      non-fatal group (75%). The mean value of procalcitonin was 1.12 ng/ml in the
      fatal group and was 0.21 ng/ml in the non-fatal group (P = 0.003). According to
      the results of our study, the procalcitonin levels in the first 2 days of the
      onset of the symptoms might be helpful for predicting fatality in CCHF patients. 

PMID- 25866109
TI  - Serologic Investigation of Hantavirus Infection in Patients with Previous
      Thrombocytopenia, and Elevated Urea and Creatinine Levels in an Epidemic Region
      of Turkey.
AB  - The first cases of Hantavirus infection in Turkey were reported in early 2009 in
      the Zonguldak and Bartin provinces. The aim of this study was to investigate the
      presence of Hantavirus antibodies in patients who had clinical and laboratory
      findings that were potentially associated with Hantavirus infection prior to the
      epidemic in Bartin in 2009. After screening 314,577 medical records from between
      2007 and 2009, the clinical and laboratory data for 442 patients meeting the
      criteria of coexistent thrombocytopenia, and elevated urea and creatinine levels
      were transferred to a statistical program. Home visits were made to 170 patients,
      84 of whom consented to participate in the study. The participants completed a
      questionnaire and provided a blood sample. Commercial anti-Hantavirus IgG and IgM
      ELISA and immunoblotting assays were used, with seropositive samples being
      confirmed by focus reduction neutralization tests (FRNT). ELISA and/or
      immunoblotting assays detected 10 positive samples; however, only 7 of these were
      recorded as positive by FRNT. FRNT positivity was significantly associated with
      female sex, the presence of a barn near to the house, and working in a forest (P
      < 0.05). In a Hantavirus endemic region, physicians must keep in mind that
      thrombocytopenia, and elevated urea and creatinine levels may indicate Hantavirus
      infection. 

PMID- 25866110
TI  - Seroprevalence of Helicobacter pylori and Hepatitis A Virus among Children in
      Rural Central Taiwan.
AB  - Helicobacter pylori and hepatitis A virus (HAV) are thought to have similar
      routes of transmission and epidemiology. This study investigated the
      seroprevalence of these 2 pathogens among children in rural, central Taiwan.
      Serum samples were collected from 856 children between 2010 and 2012 and levels
      of anti-HAV and anti-H. pylori antibodies were measured by ELISA. Questionnaires
      were used to investigate possible risk factors. The overall H. pylori and HAV
      infection rates were 6% and 0.8%, respectively. There was a significant
      difference in H. pylori infection rates (P value=0.008), but not HAV infection
      rates, between different age groups. H. pylori infection rates were significantly
      higher in children whose mothers had lower education levels. In contrast, HAV
      infection rates were significantly higher in children whose fathers had lower
      education levels. The risk of HAV infection was also 14.20-fold higher in
      children whose family members had traveled to China or Southeast Asia. No
      significant correlation was found between H. pylori and HAV seropositivity. The
      seroprevalences of H. pylori and HAV were low in rural central Taiwan. Universal
      HAV vaccination is highly recommended to prevent outbreak due to low
      seroprevalence. 

PMID- 25866111
TI  - Virulence Characteristics and Antibiotic Resistance Patterns among Various
      Phylogenetic Groups of Uropathogenic Escherichia coli Isolates.
AB  - The aim of this study was to determine the resistance patterns of uropathogenic
      Escherichia coli (UPEC) isolates and to investigate the frequency of several
      virulence genes, including fimH, papA, hlyD, cnf-1, sitA, and tsh, among various
      phylogenetic groups of UPEC isolates. A total of 85 E. coli isolates were
      recovered from urine samples from outpatients with a clinical diagnosis of
      uncomplicated urinary tract infections. A molecular approach to examine the
      antimicrobial resistance patterns was employed using PCR and the disc diffusion
      method. The detected frequencies of the virulence factor genes determined using
      PCR were: fimH (34.1%), papA (9.4%), hlyD (21.2%), cnf-1 (3.5%), sitA (15.3%),
      and tsh (27.1%). These results revealed that the isolates were resistant to
      trimethoprim-sulfamethoxazole (SXT) (74.1%), cefotaxime (CTX) (68.2%), and
      amoxicillin-clavulanic acid (AMC) (94.1%), and they were relatively less
      resistant to N (56.5%). According to these results, further investigation is
      needed to determine exactly whether or not SXT, CTX, and AMC are appropriate
      antibiotics for the treatment of UPEC infections in southern Iran. Although these
      results demonstrate that fimH is the most frequent virulence gene among UPEC
      isolates, the high prevalence of isolates that do not encode fimH (75.9%) and the
      relatively low frequency of isolates that carry other virulence genes require
      further investigation to clarify the role of the other potential virulence
      factors in the pathogenesis of these isolates. 

PMID- 25866112
TI  - Attack Rate in Food Poisoning: Order in Chaos.
AB  - The frequency distributions of the numbers of patients and eaters were near
      lognormal for almost all food poisonings. The medians and ranges remained almost
      unchanged over time, although the annual number of incidents varied. However, the
      numbers of patients and eaters were not correlated for many of the food
      poisonings. A regular pattern relating the numbers of patients and eaters emerged
      for food poisonings exhibited strong seasonal incidence. For example, food
      poisonings caused by norovirus or Campylobacter spp. exhibited a comb teeth-like
      pattern in the plot comparing the ranking numbers of patients and that of eaters,
      and fingerprint-like pattern in the plots comparing the attack rate and number of
      patients or eaters. Meanwhile, food poisonings with low incidence and without
      seasonality, such as those caused by Clostridium perfringens, exhibited amorphous
      patterns in both plots. Further analysis indicated the occurrence of these
      patterns was determined by the combination of pathogens and services, and not by
      either factor alone. Thus, the emergence of a regular pattern may be associated
      with "complexity" nature of food poisoning. 

PMID- 25866113
TI  - Transient Bacteremia Due to Streptococcus gallolyticus Subsp. pasteurianus in a 3
      Year-Old Infant.

PMID- 25866114
TI  - Novel IMB-ELISA Assay for Rapid Diagnosis of Human Toxoplasmosis Using SAG1
      Antigen.
AB  - Nanotechnology is important for medical diagnosis. Various nanoparticles have
      presented tremendous potential for diagnosing disease markers, pre-cancerous
      cells, fragment of viruses, specific proteins, antibodies, and other disease
      indicators. In general, nanoparticles are smaller than 1,000 nm and produced from
      different materials in different shapes such as spheres, rods, wires, and tubes.
      Our study aimed to develop a novel antigen-capture immunoassay based on IgG
      polyclonal antibody-coated magnetic microbead nanoparticles for the rapid
      detection of circulating surface antigen 1 of Toxoplasma gondii in human serum
      samples. Sandwich ELISA elicited a sensitivity of 92%, a specificity of 92.7%, a
      positive predictive value (PPV) of 92%, and a negative predictive value (NPV) of
      92.7%. Immunomagnetic bead-ELISA showed sensitivity (98%), specificity (96.4%),
      PPV (96%), and NPV (98.1%) higher than that of sandwich ELISA. It is obvious that
      the use of magnetic microbead nanoparticles offers the potential advantage of
      improving the diagnostic testing of toxoplasmosis. 

PMID- 25866115
TI  - Loop-Mediated Isothermal Amplification (LAMP) for Detection of Campylobacter
      jejuni and C. coli in Thai Children with Diarrhea.
AB  - Campylobacter species are common causes of bacterial diarrhea, and Campylobacter
      jejuni and C. coli are known as the predominant causative agents in humans.
      Recent studies suggested that loop-mediated isothermal amplification (LAMP) is an
      efficient and practical tool for rapid detection of C. jejuni and C. coli in
      clinical samples. We used LAMP to screen 151 stool samples for Campylobacter;
      these samples were collected in 2012 from Thai children with diarrhea. The PCR
      method discriminated C. jejuni and C. coli among the detected Campylobacter
      strains; these species were subjected to sequencing of the hipO gene (in C.
      jejuni) or the ask gene (in C. coli). The results suggest that the prevalence of
      Campylobacter infection among Thai children with diarrhea is 8.6%, and C. jejuni
      is the most prevalent species. 

PMID- 25866116
TI  - Inhibition of Autophagy by MiR-30A Induced by Mycobacteria tuberculosis as a
      Possible Mechanism of Immune Escape in Human Macrophages.
AB  - The regulatory mechanism of miRNA induction in response to Mycobacterium
      tuberculosis (MTB) infection has not been clearly established. Autophagy has
      recently been identified as an effective way to control intracellular survival of
      MTB. In the present study, we demonstrate a novel role of miR-30A in the negative
      regulation of the autophagy-mediated anti-MTB response. We found that
      overexpression of miR-30A suppresses the elimination of intracellular MTB through
      the inhibition of autophagy. Furthermore, there was a negative correlation
      between concentrations of miR-30A and beclin-1 in MTB positive patients and miR
      30A expression decreased after anti-TB treatment. Our results indicate that miR
      30A plays a key role in immune response against MTB and, therefore, may serve as
      a potential target for future treatments of tuberculosis infection. 

PMID- 25866118
TI  - Enhanced Resistance to Several Abiotic Stresses in Vibrio cholerae during
      Starvation.
AB  - In this study, we investigated whether Vibrio cholerae cells exposed to nutrient
      limited conditions developed resistance to abiotic stresses because of which
      most, if not all, starved cells turn coccoid in shape and exhibited marked
      resistance to freezing, low pH, and chlorine, but not against bile. 

PMID- 25866117
TI  - Osteopontin Exacerbates Pulmonary Damage in Influenza-Induced Lung Injury.
AB  - The level of osteopontin (OPN) increases during bacterial lung infection.
      However, the OPN level in virus-induced lung injury is unclear, and the
      relationship between the hyer-production of OPN and lung injury remains to be
      thoroughly understood. Therefore, we sought to determine whether a relationship
      exists between OPN and pulmonary damage. Particularly, pulmonary edema and the
      destruction of pulmonary tissue. In this study, we found that the OPN level was
      significantly elevated in patients with pulmonary damage, and there was a
      positive correlation between the OPN serum level and disease severity in
      influenza lung injury. The epithelial sodium channel (ENaC) is the main mechanism
      of clearance of pulmonary edema fluid, and matrix metalloproteinase 7 (MMP7) can
      degrade the extracellular matrix. In lung epithelial cells, OPN markedly
      decreased the mRNA expression of the alpha-subunit of ENaC through integrin beta3
      and CD44 (OPN receptors); however, the expression of MMP7 was promoted by OPN
      interaction with integrin beta1 and CD44. In addition, OPN increased the levels
      of tumor necrosis factor-alpha and interleukin-6. These findings suggested that
      OPN might increase influenza virus-induced lung injury by augmenting lung
      epithelial cell apoptosis and impairing ENaC and extracellular matrix
      destruction. 

PMID- 25866119
TI  - Development and Evaluation of an in-House IgM-Capture ELISA for the Detection of
      Chikungunya and Its Application to a Dengue Outbreak Situation in Kenya in 2013.
AB  - Chikungunya (CHIK) is a mosquito-borne viral disease. In the 2004 CHIK outbreak
      in Kenya, diagnosis was delayed because of the lack of accurate diagnostics.
      Therefore, this study aimed to develop and evaluate an in-house IgM-capture
      enzyme linked immunosorbent assay (ELISA) (in-house ELISA) for the detection of
      chikungunya virus (CHIKV) infections. Anti-CHIKV antibodies were raised in
      rabbits, purified and conjugated to horseradish peroxidase. These anti-CHIKV
      antibodies and cell-culture derived antigen were used to develop the ELISA. To
      validate the in-house ELISA, 148 patient sera from the 2005 Comoros CHIK outbreak
      were tested with centers for disease control and prevention (CDC) IgM-capture
      ELISA (CDC ELISA) and focus reduction neutralization test (FRNT) as reference
      assays. The in-house ELISA had a sensitivity of 97.6% and specificity of 81.3%
      compared to the CDC ELISA and a sensitivity of 91.1% and specificity of 96.7%
      compared to FRNT. Furthermore, 254 clinically suspected dengue patient samples
      from Eastern Kenya, collected in 2013, were tested for CHIKV IgM using the in
      house ELISA. Out of the 254 samples, 26 (10.2%) were IgM positive, and of these
      26 samples, 17 were further analyzed by FRNT and 14 (82.4%) were positive. The in
      house ELISA was able to diagnose CHIKV infection among suspected dengue cases in
      the 2013 outbreak. 

PMID- 25866120
TI  - Social Impact of Stigma Regarding Tuberculosis Hindering Adherence to Treatment:
      A Cross Sectional Study Involving Tuberculosis Patients in Rajshahi City,
      Bangladesh.
AB  - Stigma, considered a social disease, is more apparent in developing societies
      which are driven by various social affairs, and influences adherence to
      treatment. The aim of the present study was to examine levels of social stigma
      related to tuberculosis (TB) in sociodemographic context and identify the effects
      of sociodemographic factors on stigma. The study sample consisted of 372 TB
      patients. Data were collected using stratified sampling with simple random
      sampling techniques. T tests, chi-square tests, and binary logistic regression
      analysis were performed to examine correlations between stigma and
      sociodemographic variables. Approximately 85.9% of patients had experienced
      stigma. The most frequent indicator of the stigma experienced by patients
      involved problems taking part in social programs (79.5%). Mean levels of stigma
      were significantly higher in women (55.5%), illiterate individuals (60.8%), and
      villagers (60.8%) relative to those of other groups. Chi-square tests revealed
      that education, monthly family income, and type of patient (pulmonary and
      extrapulmonary) were significantly associated with stigma. Binary logistic
      regression analysis demonstrated that stigma was influenced by sex, education,
      and type of patient. Stigma is one of the most important barriers to treatment
      adherence. Therefore, in interventions that aim to reduce stigma, strong
      collaboration between various institutions is essential. 

PMID- 25866121
TI  - Bridgehead invasion of a monomorphic plant pathogenic bacterium: Xanthomonas
      citri pv. citri, an emerging citrus pathogen in Mali and Burkina Faso.
AB  - Molecular epidemiology studies further our understanding of migrations of
      phytopathogenic bacteria, the major determining factor in their emergence.
      Asiatic citrus canker, caused by Xanthomonas citri pv. citri, was recently
      reported in Mali and Burkina Faso, a region remote from other contaminated areas.
      To identify the origin and pathways of these emergences, we used two sets of
      markers, minisatellites and microsatellites, for investigating different
      evolutionary scales. Minisatellite typing suggested the introduction of two
      groups of strains in Mali (DAPC 1 and DAPC 2), consistent with microsatellite
      typing. DAPC 2 was restricted to Bamako district, whereas DAPC 1 strains were
      found much more invasive. The latter strains formed a major clonal complex based
      on microsatellite data with the primary and secondary founders detected in
      commercial citrus nurseries and orchards. This suggests that human activities
      played a major role in the spread of DAPC 1 strains via the movement of
      contaminated propagative material, further supported by the frequent lack of
      differentiation between populations from geographically distant nurseries and
      orchards. Approximate Bayesian Computation analyses supported the hypothesis that
      strains from Burkina Faso resulted from a bridgehead invasion from Mali. Multi
      locus variable number of tandem repeat analysis and Approximate Bayesian
      Computation are useful for understanding invasion routes and pathways of
      monomorphic bacterial pathogens. 

PMID- 25866122
TI  - Drug repurposing and emerging adjunctive treatments for schizophrenia.
AB  - INTRODUCTION: Schizophrenia is a frequent disorder, which substantially impairs
      patients' quality of life. Moreover, the burden of illness for patients, their
      families and for the society, in general, is substantial. Nevertheless, the
      understanding of the pathophysiology of this syndrome, concise diagnostic methods
      and more effective and tolerable treatments are still lacking. Thus, innovative
      approaches and the exploration of new territories are required. AREAS COVERED: An
      overview of repurposed drugs and emerging treatments for schizophrenia is
      presented, focusing on randomized, controlled trials and meta-analyses. EXPERT
      OPINION: Despite many years of drug research, several needs in the treatment of
      schizophrenia including the safety and tolerability, stage-dependent and
      personalized approaches, as well as drug delivery and sustainability have not
      been addressed sufficiently. Given the current failure of a number of
      mechanistically new drugs, repurposed compounds may serve as alternative and/or
      adjunctive agents for schizophrenic patients and for treatment refractory
      patients in particular. Anti-inflammatory drugs (e.g., acetylsalicylic acid,
      celecoxib and minocycline), as well as N-acetylcysteine, a precursor of the major
      antioxidant glutathione, hormones (e.g., estrogen, raloxifene and oxytocin),
      glutamatergic (e.g., glycine and d-serine) and nicotinergic compounds,
      'nutraceuticals' (e.g., omega-3 fatty acids) and cannabidiol, an
      endocannabinoidmodulator, represent promising agents in this field.

PMID- 25866123
TI  - Social Connections for Older People with Intellectual Disability in Ireland:
      Results from Wave One of IDS-TILDA.
AB  - BACKGROUND: The literature on influences of community versus congregated settings
      raises questions about how social inclusion can be optimised for people with
      intellectual disability. This study examines social contacts for older people
      with intellectual disability in Ireland, examining differences in social
      connection for adults with intellectual disability and other adults. MATERIALS &
      METHODS: Data were drawn from the IDS-TILDA study in Ireland. A nationally
      representative sample (n = 753) included adults aged 40 years and older, with
      additional comparison with general population participants. Predictors of social
      contacts were explored. RESULTS: Residence, level of intellectual disability and
      age were significant factors determining social contact. People in institutional
      residences, older respondents and those with severe/profound intellectual
      disability had the lowest levels of contact; older adults with intellectual
      disability had much lower rates than general population counterparts.
      CONCLUSIONS: Community-dwelling people with intellectual disability have greater
      social contact than those living in institutions, but levels are below those for
      other adults in Ireland.

PMID- 25866124
TI  - Emerging commercial molecular tests for the diagnosis of bloodstream infection.
AB  - Bloodstream infection (BSI) by microorganisms can lead to sepsis. This condition
      has a high mortality rate, which rises significantly with delays in initiation of
      appropriate antimicrobial treatment. Current culture methods for diagnosing BSI
      have long turnaround times and poor clinical sensitivity. While clinicians wait
      for culture diagnosis, patients are treated empirically, which can result in
      inappropriate treatment, undesirable side effects and contribute to drug
      resistance development. Molecular diagnostics assays that target pathogen DNA can
      identify pathogens and resistance markers within hours. Early diagnosis improves
      antibiotic stewardship and is associated with favorable clinical outcomes.
      Nonetheless, limitations of current molecular diagnostic methods are substantial.
      This article reviews recent commercially available molecular methods that use
      pathogen DNA to diagnose BSI, either by testing positive blood cultures or
      directly testing patient blood. We critically assess these tests and their
      application in clinical microbiology. A view of future directions in BSI
      diagnosis is also provided. 

PMID- 25866125
TI  - In Vivo Hemodynamic Performance Evaluation of Novel Electrocardiogram
      Synchronized Pulsatile and Nonpulsatile Extracorporeal Life Support Systems in an
      Adult Swine Model.
AB  - The primary objective of this study was to evaluate a novel electrocardiogram
      (ECG)-synchronized pulsatile extracorporeal life support (ECLS) system for adult
      partial mechanical circulatory support for adequate quality of pulsatility and
      enhanced hemodynamic energy generation in an in vivo animal model. The secondary
      aim was to assess end-organ protection during nonpulsatile versus synchronized
      pulsatile flow mode. Ten adult swine were randomly divided into a nonpulsatile
      group (NP, n = 5) and pulsatile group (P, n = 5), and placed on ECLS for 24 h
      using an i-cor system consisting of an i-cor diagonal pump, an iLA membrane
      ventilator, an 18 Fr femoral arterial cannula and a 23/25 Fr femoral venous
      cannula. Trials were conducted at a flow rate of 2.5 L/min using nonpulsatile or
      pulsatile mode (with assist ratio 1:1). Real-time pressure and flow data were
      recorded using a custom-based data acquisition system. To the best of our
      knowledge, the oxygenator and circuit pressure drops were the lowest for any
      available system in both groups. The ECG-synchronized i-cor ECLS system was able
      to trigger pulsatile flow in the porcine model. After 24-h ECLS, energy
      equivalent pressure, surplus hemodynamic energy, and total hemodynamic energy at
      preoxygenator and prearterial cannula sites were significantly higher in the P
      group than those in the NP group (P < 0.05). Urine output was higher in P versus
      NP (3379 +/- 443 mL vs. NP, 2598 +/- 1012 mL), and the P group seemed to require
      less inotropic support, but both did not reach statistical significances (P >
      0.05). The novel i-cor system performed well in the nonpulsatile and ECG
      synchronized pulsatile mode in an adult animal ECLS model. The iLA membrane
      oxygenator had an extremely lower transmembrane pressure gradient and excellent
      gas exchange capability. Our findings suggest that ECG-triggered pulsatile ECLS
      provides superior end-organ protection with improved renal function and systemic
      vascular tone. 

PMID- 25866127
TI  - Bisulfite pretreatment changes the structure and properties of oil palm empty
      fruit bunch to improve enzymatic hydrolysis and bioethanol production.
AB  - Bisulfite pretreatment is a proven effective method for improving the enzymatic
      hydrolysis of empty fruit bunch (EFB) from oil palm for bioethanol production. In
      this study, we set out to determine the changes that occur in the structure and
      properties of EFB materials and fractions of hemicellulose and lignin during the
      bisulfite pretreatment process. The results showed that the crystallinity of
      cellulose in EFB increased after bisulfite pretreatment, whereas the EFB surface
      was damaged to various degrees. The orderly structure of EFB, which was
      maintained by hydrogen bonds, was destroyed by bisulfite pretreatment. Bisulfite
      pretreatment also hydrolyzed the glycosidic bonds of the xylan backbone of
      hemicellulose, thereby decreasing the molecular weight and shortening the xylan
      chains. The lignin fractions obtained from EFB and pretreated EFB were typically
      G-S lignin, and with low content of H units. Meanwhile, de-etherification
      occurred at the beta-O-4 linkage, which was accompanied by polymerization and
      demethoxylation as a result of bisulfite pretreatment. The adsorption ability of
      cellulase differed for the various lignin fractions, and the water-soluble lignin
      fractions had higher adsorption capacity on cellulase than the milled wood
      lignin. In general, the changes in the structure and properties of EFB provided
      insight into the benefits of bisulfite pretreatment. 

PMID- 25866126
TI  - Age and sex-specific mortality of wild and captive populations of a monogamous
      pair-bonded primate (Aotus azarae).
AB  - In polygynous primates, a greater reproductive variance in males have been linked
      to their reduced life expectancy relative to females. The mortality patterns of
      monogamous pair-bonded primates, however, are less clear. We analyzed the sex
      differences in mortality within wild (NMales  = 70, NFemales  = 73) and captive
      (NMales  = 25, NFemales  = 29) populations of Azara's owl monkeys (Aotus azarae),
      a socially and genetically monogamous primate exhibiting biparental care. We used
      Bayesian Survival Trajectory Analysis (BaSTA) to test age-dependent models of
      mortality. The wild and captive populations were best fit by the logistic and
      Gompertz models, respectively, implying greater heterogeneity in the wild
      environment likely due to harsher conditions. We found that age patterns of
      mortality were similar between the sexes in both populations. We calculated life
      expectancy and disparity, the latter a measure of the steepness of senescence,
      for both sexes in each population. Males and females had similar life
      expectancies in both populations; the wild population overall having a shorter
      life expectancy than the captive one. Furthermore, captive females had a reduced
      life disparity relative to captive males and to both sexes in the wild. We
      interpret this pattern in light of the hazards associated with reproduction. In
      captivity, where reproduction is intensely managed, the risks associated with
      gestation and birth are tempered so that there is a reduction in the likelihood
      of captive females dying prematurely, decreasing their overall life disparity.

PMID- 25866128
TI  - Molecular characterization of Salmonella enterica isolates associated with
      starling-livestock interactions.
AB  - Bird-livestock interactions have been implicated as potential sources for
      bacteria within concentrated animal feeding operations (CAFO). In this study we
      characterized XbaI-digested genomic DNA from Salmonella enterica using pulsed
      field gel electrophoresis (PFGE). The PFGE analysis was conducted using 182 S.
      enterica isolates collected from a single CAFO between 2009 and 2012. Samples
      collected in 2012 were subjected to antimicrobial susceptibility testing. The
      analysis was limited to S. enterica serotypes, with at least 10 isolates, known
      to occur in both European starlings (Sturnus vulgaris) and cattle (Bos taurus)
      within this CAFO. A total of five different serotypes were screened; S. Anatum,
      S. Kentucky, S. Meleagridis, S. Montevideo, S. Muenchen. These samples were
      recovered from five different sample types; starling gastrointestinal tracts
      (GI), starling external wash, cattle feces, cattle feed and cattle water troughs.
      Indistinguishable S. enterica PFGE profiles were recovered from isolates
      originating in all sample types. Antimicrobial resistance (AMR) was also
      associated with indistinguishable S. enterica isolates recovered from all samples
      types. These data suggests that AMR S. enterica is transmitted between cattle and
      starlings and that shared feed sources are likely contributing to infections
      within both species. Moreover we isolated indistinguishable PFGE profiles across
      all years of data collection, suggesting long-term environmental persistence may
      be mediated by starling visits to CAFO. 

PMID- 25866129
TI  - Exposure to environmental stressors result in increased viral load and further
      reduction of production parameters in pigs experimentally infected with PCV2b.
AB  - Porcine circovirus type 2 (PCV2) has been identified as the essential, but not
      sole, underlying infectious component for PCV-associated diseases (PCVAD).
      Several co-factors have been suggested to convert an infection with PCV2 into the
      clinical signs of PCVAD, including co-infection with a secondary pathogen and the
      genetic background of the pig. In the present study, we investigated the role of
      environmental stressors in the form of changes in environmental temperature and
      increased stocking-density on viral load in serum and tissue, average daily
      weight gain (ADG) and food conversion rate (FCR) of pigs experimentally infected
      with a defined PCV2b strain over an eight week period. These stressors were
      identified recently as risk factors leading to the occurrence of severe PCVAD on
      a farm level. In the current study, PCV2-free pigs were housed in separate,
      environmentally controlled rooms, and the experiment was performed in a 2*2
      factorial design. In general, PCV2b infection reduced ADG and increased FCR, and
      these were further impacted on by the environmental stressors. Furthermore, all
      stressors led to an increased viral load in serum and tissue as assessed by qPCR,
      although levels did not reach statistical significance. Our data suggest that
      there is no need for an additional pathogen to develop PCVAD in conventional
      status pigs, and growth retardation and clinical signs can be induced in PCV2
      infected pigs that are exposed to environmental stressors alone. 

PMID- 25866130
TI  - Gender-specific association of weight perception and appearance satisfaction with
      slimming attempts and eating patterns in a sample of young Norwegian adolescents.
AB  - OBJECTIVE: To examine gender-specific associations of weight perception and
      appearance satisfaction with slimming attempts and eating patterns among young
      Norwegian adolescents. DESIGN: Cross-sectional study. Adolescent dietary data
      were reported by parents using a retrospective FFQ. Eating patterns were
      identified using principal component analysis. Adolescents' reported weight
      perception, appearance satisfaction and slimming attempts were analysed using
      cross-tabulation and Pearson's chi 2 test. Associations between perceived weight,
      appearance satisfaction and slimming attempts/eating patterns were examined using
      multiple logistic regression analysis. SETTING: Primary schools, Telemark,
      Norway. SUBJECTS: Children (n 469), mean age 12.7 (sd 0.3) years, and parents.
      RESULTS: Gender differences were observed in self-perceived weight and appearance
      satisfaction. Girls were most satisfied with appearance when feeling thin, boys
      when feeling just the right weight. Perceived overweight was the main predictor
      of slimming attempts across genders (adjusted OR=15.3; 95 % CI 6.0, 39.1 for
      girls; adjusted OR=18.2; 95 % CI 5.8, 57.3 for boys). Low appearance satisfaction
      was associated with slimming attempts (adjusted OR=3.3; 95 % CI 1.0, 10.5) and a
      dieting eating pattern (adjusted OR=2.8; 95 % CI 1.5, 5.2) in girls. Perceived
      underweight was associated with a junk/convenience eating pattern in boys
      (adjusted OR=2.8; 95 % CI 1.2, 6.4). CONCLUSIONS: Gender differences were
      observed in subjective body concerns. Perceived overweight was the main predictor
      of slimming attempts by both genders. Different aspects of body dissatisfaction
      were related to different food behaviours in boys and girls. Health professionals
      should be aware of these gender differences when planning health promotion
      programmes targeting young adolescents.

PMID- 25866131
TI  - [Posterior reversible encephalopathy syndrome after neurosurgery: A literature
      review].
AB  - Posterior reversible encephalopathy syndrome is a clinical-radiological
      characterized by decreased level of consciousness, seizures, and visual
      disturbances, as well as radiologically ras brain edema, predominantly in parieto
      occipital white matter regions. There are many situations that can trigger the
      disorder, including the administration of immunosuppressants, chemotherapy
      agents, hypertensive disorders, and sepsis. The case is described of a patient
      diagnosed with stage IV prostate adenocarcinoma, receiving chemotherapy,
      andundergoing a posterior reversible encephalopathy syndrome after surgery for
      resection of brain metastasis. 

PMID- 25866132
TI  - [Central blockades in Pediatrics: A review of current literature].
AB  - Pediatric neuraxial anesthesia is an effective tool that can be used as a
      supplement or alternative to general anesthesia. However, there have always been
      doubts about its usefulness and risk-benefit ratio. The purpose of this review is
      to describe the current role of central blockades in pediatric patients, upgrade
      practical and safety aspects, and review the latest technological advances
      applied to this procedure. 

PMID- 25866133
TI  - Mechanochemical reactions studied by in situ Raman spectroscopy: base catalysis
      in liquid-assisted grinding.
AB  - In situ Raman spectroscopy was employed to study the course of a mechanochemical
      nucleophilic substitution on a carbonyl group. We describe evidence of base
      catalysis, akin to catalysis in solution, achieved by liquid-assisted grinding. 

PMID- 25866134
TI  - Effect of maintaining apical patency on endodontic pain in posterior teeth with
      pulp necrosis and apical periodontitis: a randomized controlled trial.
AB  - AIM: To evaluate the association between apical patency and post-operative pain
      in posterior teeth with pulp necrosis and apical periodontitis. METHODOLOGY:
      Sixty-eight patients requiring primary root canal treatment in mandibular first
      molars with necrotic pulps and apical periodontitis were included. The patients
      were randomly allocated to one of two groups: patency (n = 34) and nonpatency (n
      = 34). After administering local anaesthesia, root canal preparation was
      completed using ProTaper rotary instruments. A size 10 K-file was used as a
      patency file and carried 1 mm beyond the working length (WL) between each
      instrument change in the patency group, while it was carried up to WL in the
      nonpatency group. Patients were asked to record their pain experience on a pain
      chart daily for 7 days. Three patients (two in the patency group, one in the
      nonpatency group) did not return with completed pain charts on the subsequent
      visit, resulting in a total of 65 patients for the final analysis (patency, n =
      32; nonpatency, n = 33). Data was analysed using Chi Square test, t-test, Mann
      Whitney test and Wilcoxon Signed Ranks test. RESULTS: Overall, 43% of the
      patients experienced post-operative pain. The patency group had less incidence of
      pain (34%) as compared to the nonpatency group (52%), but the difference was not
      significant (P = 0.163). CONCLUSION: Maintenance of apical patency during
      chemomechanical preparation had no significant influence on post-operative pain
      in posterior teeth with necrotic pulps and apical periodontitis.

PMID- 25866136
TI  - The effect of slightly warm temperature on work performance and comfort in open
      plan offices - a laboratory study.
AB  - The aim of the study was to determine the effect of a temperature of 29 degrees C
      on performance in tasks involving different cognitive demands and to assess the
      effect on perceived performance, subjective workload, thermal comfort, perceived
      working conditions, cognitive fatigue, and somatic symptoms in a laboratory with
      realistic office environment. A comparison was made with a temperature of 23
      degrees C. Performance was measured on the basis of six different tasks that
      reflect different stages of cognitive performance. Thirty-three students
      participated in the experiment. The exposure time was 3.5 h in both thermal
      conditions. Performance was negatively affected by slightly warm temperature in
      the N-back working memory task. Temperature had no effect on performance in other
      tasks focusing on psychomotor, working memory, attention, or long-term memory
      capabilities. Temperature had no effect on perceived performance. However,
      slightly warm temperature caused concentration difficulties. Throat symptoms were
      found to increase over time at 29 degrees C, but no temporal change was seen at
      23 degrees C. No effect of temperature on other symptoms was found. As expected,
      the differences in thermal comfort were significant. Women perceived a
      temperature of 23 degrees C colder than men. 

PMID- 25866135
TI  - Prion-like transmission of neuronal huntingtin aggregates to phagocytic glia in
      the Drosophila brain.
AB  - The brain has a limited capacity to self-protect against protein aggregate
      associated pathology, and mounting evidence supports a role for phagocytic glia
      in this process. We have established a Drosophila model to investigate the role
      of phagocytic glia in clearance of neuronal mutant huntingtin (Htt) aggregates
      associated with Huntington disease. We find that glia regulate steady-state
      numbers of Htt aggregates expressed in neurons through a clearance mechanism that
      requires the glial scavenger receptor Draper and downstream phagocytic engulfment
      machinery. Remarkably, some of these engulfed neuronal Htt aggregates effect
      prion-like conversion of soluble, wild-type Htt in the glial cytoplasm. We
      provide genetic evidence that this conversion depends strictly on the Draper
      signalling pathway, unveiling a previously unanticipated role for phagocytosis in
      transfer of pathogenic protein aggregates in an intact brain. These results
      suggest a potential mechanism by which phagocytic glia contribute to both protein
      aggregate-related neuroprotection and pathogenesis in neurodegenerative disease. 

PMID- 25866137
TI  - Polyunsaturated fatty acids incorporation into cardiolipin in H9c2 cardiac
      myoblast.
AB  - Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), known as omega-3
      polyunsaturated fatty acid (PUFA), are common nutrients in daily food intake and
      have been shown to prevent cardiovascular disease and improve cardiac functions.
      Cardiolipin is a mitochondrial phospholipid necessary for maintaining
      physiological function of mitochondria. Several studies have indicated that the
      cardiolipin acyl chain compositions affect the function of cardiolipin and
      mitochondria. Here, we investigated the structural changes of cardiolipin after
      DHA and EPA supplementation and compared them to arachidonic acid (AA) treatment.
      H9c2 cardiac myoblast was used as a cell model, and cardiolipin species was
      monitored and identified via LC-MS and MS/MS. Our results showed distinct mass
      envelopes of cardiolipin with the same carbon number but different double bonds
      in mass spectrum. There were 116 cardiolipin species with 36 distinct mass in 6
      mass envelopes identified by MS/MS. Three days of PUFA treatment resulted in
      decreases of low-molecular-weight cardiolipin and increases of high-molecular
      weight cardiolipin, suggesting the incorporation of exogenous DHA, EPA and AA
      into mitochondrial cardiolipin. PUFA incorporation was further verified by MS/MS
      analysis. More importantly, we found that DHA supplementation elevated the
      percent content of less unsaturated cardiolipin species and highly unsaturated
      cardiolipin species, containing omega-3 fatty acyl chains, indicating a omega-3
      fatty acid incorporation mechanism with peroxidation protection. Our results
      indicate that PUFA supplementation differentially perturbed the fatty acyl chain
      compositions in the mitochondrial cardiolipin in the H9c2 cardiac myoblast,
      suggesting that mitochondrial membrane and the function of mitochondria are
      susceptible to exogenous lipid species. 

PMID- 25866138
TI  - Primary sclerosing cholangitis - the Norwegian experience.
AB  - Research related to primary sclerosing cholangitis (PSC) has since 1980 been a
      major activity at the Oslo University Hospital Rikshospitalet. The purpose of
      this publication is to describe the development of this research, the impact of
      this research on the clinical handling of the patients, and finally to describe
      what we believe are the most urgent, remaining problems to be solved. During the
      early years, our research dealt primarily with clinical aspects of the disease.
      The concomitant inflammatory bowel disease (IBD) seen in most patients with PSC
      was a major interest and we also started looking into genetic associations of
      PSC. Prognosis, malignancy development and treatment with special emphasis on
      transplantation have later been dealt with. These activities has had impact on
      several aspects of PSC management; when and how to diagnose PSC and variant forms
      of PSC, how to handle IBD in PSC and how to deal with the increased rate of
      malignancy? The problems remaining to be solved are many. What is the role of the
      gut and the gut microbiota in the development of PSC? Do the PSC patients have an
      underlying disturbance in the bile homeostasis? And how does the characteristic
      type of fibrosis in PSC develop? The genetic studies have supported a role for
      the adaptive immune system in the disease development, but how should this be
      dealt with? Importantly, the development of malignancy in PSC is still not
      understood, and we lack appropriate medical treatment for our patients. 

PMID- 25866139
TI  - Warming of intravenous and irrigation fluids for preventing inadvertent
      perioperative hypothermia.
AB  - BACKGROUND: Inadvertent perioperative hypothermia (a drop in core temperature to
      below 36 degrees C) occurs because of interference with normal temperature
      regulation by anaesthetic drugs, exposure of skin for prolonged periods and
      receipt of large volumes of intravenous and irrigation fluids. If the temperature
      of these fluids is below core body temperature, they can cause significant heat
      loss. Warming intravenous and irrigation fluids to core body temperature or above
      might prevent some of this heat loss and subsequent hypothermia. OBJECTIVES: To
      estimate the effectiveness of preoperative or intraoperative warming, or both, of
      intravenous and irrigation fluids in preventing perioperative hypothermia and its
      complications during surgery in adults. SEARCH METHODS: We searched the Cochrane
      Central Register of Controlled Trials (CENTRAL) (2014, Issue 2), MEDLINE Ovid SP
      (1956 to 4 February 2014), EMBASE Ovid SP (1982 to 4 February 2014), the
      Institute for Scientific Information (ISI) Web of Science (1950 to 4 February
      2014), Cumulative Index to Nursing and Allied Health Literature (CINAHL)
      EBSCOhost (1980 to 4 February 2014) and reference lists of identified articles.
      We also searched the Current Controlled Trials website and ClinicalTrials.gov.
      SELECTION CRITERIA: We included randomized controlled trials or quasi-randomized
      controlled trials comparing fluid warming methods versus standard care or versus
      other warming methods used to maintain normothermia. DATA COLLECTION AND
      ANALYSIS: Two review authors independently extracted data from eligible trials
      and settled disputes with a third review author. We contacted study authors to
      ask for additional details when needed. We collected data on adverse events only
      if they were reported in the trials. MAIN RESULTS: We included in this review 24
      studies with a total of 1250 participants. The trials included various numbers
      and types of participants. Investigators used a range of methods to warm fluids
      to temperatures between 37 degrees C and 41 degrees C. We found that evidence was
      of moderate quality because descriptions of trial design were often unclear,
      resulting in high or unclear risk of bias due to inappropriate or unclear
      randomization and blinding procedures. These factors may have influenced results
      in some way. Our protocol specified the risk of hypothermia as the primary
      outcome; as no trials reported this, we decided to include data related to mean
      core temperature. The only secondary outcome reported in the trials that provided
      useable data was shivering. Evidence was unclear regarding the effects of fluid
      warming on bleeding. No data were reported on our other specified outcomes of
      cardiovascular complications, infection, pressure ulcers, bleeding, mortality,
      length of stay, unplanned intensive care admission and adverse events.Researchers
      found that warmed intravenous fluids kept the core temperature of study
      participants about half a degree warmer than that of participants given room
      temperature intravenous fluids at 30, 60, 90 and 120 minutes, and at the end of
      surgery. Warmed intravenous fluids also further reduced the risk of shivering
      compared with room temperature intravenous fluidsInvestigators reported no
      statistically significant differences in core body temperature or shivering
      between individuals given warmed and room temperature irrigation fluids. AUTHORS'
      CONCLUSIONS: Warm intravenous fluids appear to keep patients warmer during
      surgery than room temperature fluids. It is unclear whether the actual
      differences in temperature are clinically meaningful, or if other benefits or
      harms are associated with the use of warmed fluids. It is also unclear if using
      fluid warming in addition to other warming methods confers any benefit, as a
      ceiling effect is likely when multiple methods of warming are used.

PMID- 25866140
TI  - Comparing single-agent with doublet chemotherapy in first-line treatment of
      advanced non-small cell lung cancer with performance status 2: a meta-analysis.
AB  - AIM: This systematic review and meta-analysis was performed to assess the
      efficacy and side effects between single-agent and doublet chemotherapy in first
      line treatment of advanced non-small cell lung cancer with performance status 2
      (PS2). METHODS: We searched for randomized controlled trials in online electronic
      databases and extracted data from eligible studies for meta-analysis. Pooled
      hazard ratio (HR) for overall survival (OS), pooled risk difference (RD) for 1
      year survival, pooled risk ratio (RR) for objective response rate (ORR) and
      adverse effects were calculated using a fixed-effect model. RESULTS: Six trials
      with 386 participants in the single-agent group and 389 participants in the
      doublet group were included in this review. Compared with single-agent
      chemotherapy, doublet significantly improved OS (HR 0.72; 95% CI 0.61-0.84; P <
      0.0001) and significantly increased 1-year survival rate (RD -0.09; 95% CI -0.14
      to -0.03; P = 0.004) and ORR (RR 0.4; 95% CI 0.30-0.69; P = 0.0002). Doublet
      chemotherapy also significantly increased the risk of grade 3/4 neutropenia (RR =
      4.97; 95% CI 2.93-8.43; P < 0.00001), thrombocytopenia (RR = 10.29; 95% CI 3.80
      27.85; P < 0.00001) and anemia (RR = 2.50; 95% CI 1.27-4.90; P = 0.008).
      CONCLUSIONS: Our study implies that carboplatin-containing doublet chemotherapy
      improved OS, 1-year survival rate and ORR, but increased the risk of grade 3/4
      hematotoxicity. Carboplatin-containing doublet may well be superior to non
      carboplatin-containing treatment.

PMID- 25866142
TI  - Regulatory T cells-derived IL-35 promotes the growth of adult acute myeloid
      leukemia blasts.
AB  - Tumor immune escape mechanism mediated by CD4+CD25+regulatory T cells (Tregs) is
      a key factor in the pathogenesis of acute myeloid leukemia (AML). IL-35, as a
      novel inhibitory cytokine, is produced by Tregs specially and regulates functions
      of Tregs in murine. However, IL-35 expression of Tregs in human is still
      disputed, and its role in AML is yet to be elucidated. In this study, we found
      that IL-35 was expressed highly in peripheral blood plasma of adult patients with
      AML and significantly correlated with the clinical stages of malignancy. Tregs
      derived from adult AML patients produced IL-35 in a stimulation-dependent manner.
      IL-35 promoted AML blasts immune escape by expanding Tregs and inhibiting
      CD4+CD25-effector T cells (Teffs). Furthermore, IL-35 directly promoted the
      proliferation of AML blasts and reduced the apoptosis of AML blasts. Together,
      our study demonstrates that IL-35-derived from Tregs promotes the growth of adult
      AML blasts, suggesting that IL-35 has an important role in the pathogenesis of
      AML. 

PMID- 25866143
TI  - Amyloidosis cutis dyschromica in two siblings and review of the epidemiology,
      clinical features and management in 48 cases.
AB  - Amyloidosis cutis dyschromica (ACD) is a rare form of primary cutaneous
      amyloidosis (PCA). There is a paucity of information in the dermatology
      literature to guide its diagnosis, investigation and treatment. We present two
      siblings with ACD and summarise the epidemiology, clinical features, natural
      history and treatments in 48 cases of ACD from the literature. Familial cases
      were more common (37) than sporadic cases. ACD is predominantly reported in those
      of East and South-East Asian ethnicity (63%). The mean age of onset was 6 years
      in familial cases, and 23 years in sporadic cases. The clinical features of
      familial and sporadic ACD do not differ substantially. Pruritus was the only
      symptom, and was reported in 19% of all cases. There were no reported ACD cases
      with systemic amyloidosis. Acitretin was reported to result in improvement in
      seven of 10 patients treated. Routine investigation for systemic involvement is
      not necessary. Acitretin may be helpful.

PMID- 25866141
TI  - Charged group surface accessibility determines micelleplexes formation and
      cellular interaction.
AB  - Micelleplexes are a class of nucleic acid carriers that have gained acceptance
      due to their size, stability, and ability to synergistically carry small
      molecules. MicroRNAs (miRNAs) are small non-coding RNA gene regulator that is
      consists of 19-22 nucleotides. Altered expression of miRNAs plays an important
      role in many human diseases. Using a model 22-nucleotide miRNA sequence, we
      investigated the interaction between charged groups on the micelle surface and
      miRNA. The model micelle system was formed from methoxy-poly(ethylene glycol)-b
      poly(lactide) (mPEG-PLA) mixed with methoxy-poly(ethylene glycol)-b-poly(lactide)
      b-oligoarginine (mPEG-PLA-Rx, x = 8 or 15). Surface properties of the micelles
      were varied by controlling the oligoarginine block length and conjugation
      density. Micelles were observed to have a core-shell conformation in the aqueous
      environment where the PLA block constituted the hydrophobic core, mPEG and
      oligoarginine formed a hydrophilic corona. Significantly different thermodynamic
      behaviors were observed during the interaction of single stranded miRNA with
      micelles of different surface properties, and the resulting micelleplexes
      mediated substantial cellular association. Depending upon the oligoarginine
      length and density, micelles exhibited miRNA loading capacity directly related to
      the presentation of charged groups on the surface. The effect of charged group
      accessibility of cationic micelle on micelleplex properties provides guidance on
      future miRNA delivery system design. 

PMID- 25866144
TI  - Professor Richard Nelson Perham.
AB  - A British molecular biologist who made groundbreaking contributions to the
      molecular structure, assembly and function of proteins and was Editor-in-Chief of
      The FEBS Journal (1998-2013). 

PMID- 25866145
TI  - Social learning promotes understanding of the physical world: Preschool
      children's imitation of weight sorting.
AB  - We investigated whether social learning, specifically imitation, can advance
      preschoolers' understanding of weight. Preschoolers were randomly assigned to
      experimental and control groups. The experimental group saw an adult
      intentionally categorize an array of four visually identical objects based on
      weight. Then, children's weight-based sorting of the objects was evaluated. To
      test generalization, children were presented with novel objects (differing in
      shape, color, and weight from the original ones) and not shown what to do with
      them. Results indicate that 48-month-olds learned to sort by weight via observing
      the adult's demonstration of categorization and that children generalized weight
      sorting to novel objects. This shows that children imitate at a more abstract
      level than merely motor actions. They learn and imitate generalizable rules. 36
      month-olds did not succeed on this weight sorting task. Children's cognitive
      development constrains what children learn through social observation and
      imitation. 

PMID- 25866146
TI  - Intraductal papillary mucinous neoplasm of the pancreas in an adult patient with
      cystic fibrosis after double-lung transplantation.
AB  - We report on an adult patient with cystic fibrosis after double-lung
      transplantation under triple immunosuppression with non-specific abdominal
      symptoms and a pancreatic cystic tumor, resulting in the diagnosis of an
      intraductal papillary mucinous neoplasm (IPMN) of the pancreas. Pancreatic cysts
      in adult patients with cystic fibrosis, especially after transplantation, merit
      close attention and thorough investigation. 

PMID- 25866147
TI  - Strain rate echocardiography uncovers subclinical left ventricular dysfunction in
      cystic fibrosis.
AB  - BACKGROUND: CFTR is expressed in cardiac myocytes. In mice, lack of CFTR alters
      cardiomyocyte contraction and Ca2+ signaling, and decreases cardiac reserve. We
      undertook a pilot study evaluating left ventricular (LV) function in CF patients
      using strain and strain rate echocardiography. METHODS: Echocardiography with
      tissue Doppler and strain and strain rate imaging were performed in 8 CF adults
      following pulmonary function tests. Results were compared to literature values
      obtained in healthy subjects. RESULTS: All CF individuals had normal LV ejection
      fractions. In contrast, 50% of men and 100% of women with CF had decreased LV
      systolic strain. Strain rates were significantly decreased in 100% of CF
      individuals. RV function was normal and LV function did not correlate with lung
      function. CONCLUSIONS: Strain and strain rate echocardiography identified LV
      systolic abnormalities in CF individuals not detected by conventional
      echocardiography. We propose that this echocardiography modality may identify
      subclinical cardiac dysfunction in CF.

PMID- 25866148
TI  - Vitamin D status and monitoring in female veterans.
AB  - An increasing number of women are serving in the military. We initiated a
      retrospective study to evaluate vitamin D status and monitoring in female
      veterans, and to examine the potential link between vitamin D status, age, race,
      post-traumatic stress disorder (PTSD), health care costs, and utilization.
      Approximately 44 percent of the 3,608 female veterans evaluated between 2001 and
      2010 were vitamin D deficient (25(OH)D < 20 ng/ml), a rate substantially higher
      than that of the general population. While younger (<55 years) and older (55+
      years) women did not differ significantly in initial vitamin D status, older
      women had significantly more vitamin D monitoring and follow-up testing than
      younger women. Approximately 44 percent of vitamin D deficient women did not
      receive follow-up vitamin D testing. Minority female veterans were most likely to
      be vitamin D deficient. Female veterans with PTSD did not differ from others
      regarding their initial vitamin D status; those that were initially deficient
      were significantly more likely to receive follow-up testing and were more likely
      to achieve a replete state. Vitamin D deficiency in female veterans was also
      associated with increased health-care costs. Appropriate monitoring and
      replacement of vitamin D should be offered to all female veterans. 

PMID- 25866149
TI  - To adjust or not to adjust for baseline when analyzing repeated binary responses?
      The case of complete data when treatment comparison at study end is of interest.
AB  - The benefits of adjusting for baseline covariates are not as straightforward with
      repeated binary responses as with continuous response variables. Therefore, in
      this study, we compared different methods for analyzing repeated binary data
      through simulations when the outcome at the study endpoint is of interest.
      Methods compared included chi-square, Fisher's exact test, covariate
      adjusted/unadjusted logistic regression (Adj.logit/Unadj.logit), covariate
      adjusted/unadjusted generalized estimating equations (Adj.GEE/Unadj.GEE),
      covariate adjusted/unadjusted generalized linear mixed model
      (Adj.GLMM/Unadj.GLMM). All these methods preserved the type I error close to the
      nominal level. Covariate adjusted methods improved power compared with the
      unadjusted methods because of the increased treatment effect estimates,
      especially when the correlation between the baseline and outcome was strong, even
      though there was an apparent increase in standard errors. Results of the Chi
      squared test were identical to those for the unadjusted logistic regression.
      Fisher's exact test was the most conservative test regarding the type I error
      rate and also with the lowest power. Without missing data, there was no gain in
      using a repeated measures approach over a simple logistic regression at the final
      time point. Analysis of results from five phase III diabetes trials of the same
      compound was consistent with the simulation findings. Therefore, covariate
      adjusted analysis is recommended for repeated binary data when the study endpoint
      is of interest.

PMID- 25866150
TI  - Prevalence of and risk factors for hypoglycemic symptoms after gastric bypass and
      sleeve gastrectomy.
AB  - OBJECTIVE: To determine the prevalence of and risk factors for postprandial
      hypoglycemic symptoms among bariatric surgery patients. METHODS: A questionnaire
      including the Edinburgh hypoglycemia scale was mailed to patients who underwent
      either Roux-en-Y gastric bypass (RYGB) or vertical sleeve gastrectomy (VSG) at a
      single center. Based on the questionnaire, the patients were categorized as
      having high or low suspicion for post surgical, postprandial hypoglycemic
      symptoms. RESULTS: Of the 1119 patients with valid addresses, 40.2% (N = 450)
      responded. Among the respondents, 34.2% had a high suspicion for symptoms of post
      bariatric surgery hypoglycemia. In multivariate analyses, in addition to female
      sex (P = 0.001), RYGB (P = 0.004), longer time since surgery (P = 0.013), and
      lack of diabetes (P = 0.040), the high suspicion group was more likely to report
      pre-operative symptoms of hypoglycemia (P < 0.001), compared to the low suspicion
      group. Similar results were observed when the high suspicion group was restricted
      to those requiring assistance from others, syncope, seizure with severe symptoms,
      or medically confirmed hypoglycemia (N = 52). CONCLUSIONS: One third of patients
      who underwent RYGB or VSG reported postprandial symptoms concerning for
      postsurgical hypoglycemia, which was related to the presence of pre-operative
      hypoglycemic symptoms. Pre-operative screening for hypoglycemic symptoms may
      identify a group of patients at increased risk of postbariatric surgery
      hypoglycemia.

PMID- 25866151
TI  - Cerebrovascular and blood-brain barrier impairments in Huntington's disease:
      Potential implications for its pathophysiology.
AB  - OBJECTIVE: Although the underlying cause of Huntington's disease (HD) is well
      established, the actual pathophysiological processes involved remain to be fully
      elucidated. In other proteinopathies such as Alzheimer's and Parkinson's
      diseases, there is evidence for impairments of the cerebral vasculature as well
      as the blood-brain barrier (BBB), which have been suggested to contribute to
      their pathophysiology. We investigated whether similar changes are also present
      in HD. METHODS: We used 3- and 7-Tesla magnetic resonance imaging as well as
      postmortem tissue analyses to assess blood vessel impairments in HD patients. Our
      findings were further investigated in the R6/2 mouse model using in situ cerebral
      perfusion, histological analysis, Western blotting, as well as transmission and
      scanning electron microscopy. RESULTS: We found mutant huntingtin protein (mHtt)
      aggregates to be present in all major components of the neurovascular unit of
      both R6/2 mice and HD patients. This was accompanied by an increase in blood
      vessel density, a reduction in blood vessel diameter, as well as BBB leakage in
      the striatum of R6/2 mice, which correlated with a reduced expression of tight
      junction-associated proteins and increased numbers of transcytotic vesicles,
      which occasionally contained mHtt aggregates. We confirmed the existence of
      similar vascular and BBB changes in HD patients. INTERPRETATION: Taken together,
      our results provide evidence for alterations in the cerebral vasculature in HD
      leading to BBB leakage, both in the R6/2 mouse model and in HD patients, a
      phenomenon that may, in turn, have important pathophysiological implications.

PMID- 25866152
TI  - Reprogramming of human somatic cells by bacteria.
AB  - In general, it had been believed that the cell fate restriction of terminally
      differentiated somatic cells was irreversible. In 1952, somatic cell nuclear
      transfer (SCNT) was introduced to study early embryonic development in frogs. So
      far, various mammalian species have been successfully cloned using the SCNT
      technique, though its efficiency is very low. Embryonic stem (ES) cells were the
      first pluripotent cells to be isolated from an embryo and have a powerful
      potential to differentiate into more than 260 types of cells. The generation of
      induced pluripotent stem (iPS) cells was a breakthrough in stem cell research,
      and the use of these iPS cells has solved problems such as low efficiency and
      cell fate restriction. These cells have since been used for clinical application,
      disease investigation, and drug selection. As it is widely accepted that the
      endosymbiosis of Archaea into eukaryotic ancestors resulted in the generation of
      eukaryotic cells, we examined whether bacterial infection could alter host cell
      fate. We previously showed that when human dermal fibroblast (HDF) cells were
      incorporated with lactic acid bacteria (LAB), the LAB-incorporated HDF cells
      formed clusters and expressed a subset of common pluripotent markers. Moreover,
      LAB-incorporated cell clusters could differentiate into cells derived from each
      of the three germinal layers both in vivo and in vitro, indicating successful
      reprogramming of host HDF cells by LAB. In the current review, we introduce the
      existing examples of cellular reprogramming by bacteria and discuss their nuclear
      reprogramming mechanisms. 

PMID- 25866153
TI  - Highly sensitive fluorescence detection of glycoprotein based on energy transfer
      between CuInS2 QDs and rhodamine B.
AB  - A highly sensitive fluorescence method for glycoprotein detection has been
      established based on fluorescence resonance energy transfer (FRET) between CuInS2
      quantum dots (QDs) and rhodamine B (RB). Lectins comprise a group of proteins
      with unique affinities toward carbohydrate structures, so the process of FRET can
      occur between lectin-coated QDs (CuInS2 QDs-Con A conjugates, acceptors) and
      carbohydrate-coated RB (RB-NH2-glu conjugates, donors). The fluorescence of
      lectin-coated QDs was recovered in the presence of a glycoprotein such as glucose
      oxidase (GOx) and transferrin (TRF), which significantly reduced the FRET
      efficiency between the donor and the acceptor. Under optimal conditions, a linear
      correlation was established between the fluorescence intensity ratio I654/I577
      and the TRF concentration over the range of 6.90 * 10(-10) to 3.45 * 10(-8)
      mol/L, with a detection limit of 2.5 * 10(-10) mol/L. The linear range for GOx is
      3.35 * 10(-10) to 6.70 * 10(-8) mol/L, with a detection limit of 1.5 * 10(-10)
      mol/L. The proposed method was applied to the determination of glycoprotein in
      human serum and cell-extract samples with satisfactory results. Furthermore,
      CuInS2  QDs-Con A conjugates are used as safe and efficient optical nanoprobes in
      HepG2 cell imaging.

PMID- 25866154
TI  - Controlling epileptiform activity with organic electronic ion pumps.
AB  - In treating epilepsy, the ideal solution is to act at a seizure's onset, but only
      in the affected regions of the brain. Here, an organic electronic ion pump is
      demonstrated, which directly delivers on-demand pure molecules to specific brain
      regions. State-of-the-art organic devices and classical pharmacology are combined
      to control pathological activity in vitro, and the results are verified with
      electrophysiological recordings. 

PMID- 25866155
TI  - Consuming Lentinula edodes (Shiitake) Mushrooms Daily Improves Human Immunity: A
      Randomized Dietary Intervention in Healthy Young Adults.
AB  - BACKGROUND: Mushrooms are widely cited for their medicinal qualities, yet very
      few human intervention studies have been done using contemporary guidelines.
      OBJECTIVE: The aim of this study was to determine whether consumption of whole,
      dried Lentinula edodes (shiitake) mushrooms could improve human immune function.
      Primary objectives were to ascertain whether L. edodes consumption would improve
      gammadelta-T cell proliferation and activation responses, quantify a dose
      response, and elicit cytokine secretion patterns. Secondary objectives included
      determining changes in natural killer T (NK-T) cell proliferation and activation,
      secretory immunoglobulin A (sIgA) in saliva, and C-reactive protein (CRP) in
      serum. DESIGN: Fifty-two healthy males and females, aged 21-41 years,
      participated in a 4-week parallel group study, consuming either 5 or 10 g of
      mushrooms daily. Each subject had blood drawn before and after 4 weeks of daily
      L. edodes consumption. Saliva and serum were also collected. Peripheral blood
      mononuclear cells were cultured in autologous serum for 24 hours or 6 days,
      stained, and examined by flow cytometry. RESULTS: Eating L. edodes for 4 weeks
      resulted in increased ex vivo proliferation of gammadelta-T (60% more, p <
      0.0001) and NK-T (2-fold more, p < 0.0001) cells. Both cell types also
      demonstrated a greater ability to express activation receptors, suggesting that
      consuming mushrooms improved cell effector function. The increase in sIgA implied
      improved gut immunity. The reduction in CRP suggested lower inflammation. The
      pattern of cytokines secreted before and after mushroom consumption was
      significantly different; consumption resulted in increased interleukin (IL)-4, IL
      10, tumor necrosis factor (TNF)-alpha, and IL-1alpha levels, a decreased
      macrophage inflammatory protein-1alpha/chemokine C-C ligand 3 (MIP-1alpha/CCL3)
      level, and no change to IL-6, IL-1beta, MIP-1beta, IL-17 and interferon (IFN)
      gamma levels. CONCLUSIONS: Regular L. edodes consumption resulted in improved
      immunity, as seen by improved cell proliferation and activation and increased
      sIgA production. The changes observed in cytokine and serum CRP levels suggest
      that these improvements occurred under conditions that were less inflammatory
      than those that existed before consumption.

PMID- 25866156
TI  - Gonadotrophic cells and gonadal sex differentiation in medaka: Characterization
      of several northern and southern strains.
AB  - Gonadotropins play an important role in gametogenesis and reproduction in
      vertebrates. Their localization in the pituitary during gonadal sex
      differentiation has been studied mainly in southern (Oryzias latipes) strains of
      medaka fish, with that in northern medaka (O. sakaizumii) remaining poorly
      understood. Hence, in this study, we characterized gonadal differentiation and
      gonadotrophic cells during sex differentiation in two northern strains (HNI and
      Kaga) and two southern strains (Hd-rR and d-rR/Tokyo). All strains exhibited
      similar sex differentiation at hatching, such as (1) sex difference in germ cell
      number (XX > XY), and (2) the transition of XX germ cells into meiosis, and (3)
      presence of glycoprotein-alpha (Gpa)-positive cells. However, follicle
      stimulating hormone-beta (Fshb)-positive cells were first detected in the
      pituitary 1 day post-hatching in HNI. Exposure to high-temperature conditions and
      to cortisol in a dose dependent manner resulted in the localization of Fshb cells
      in the pituitary at hatching. This study demonstrates differences in gonadotropin
      subunit expression between northern and southern strains of medaka, and suggests
      that Fsh is not involved in early gonadal sex differentiation, such as the sex
      difference in germ cell number, and that high-temperature induce Fshb expression
      via cortisol production in medaka.

PMID- 25866157
TI  - Ex vivo gene therapy using patient iPSC-derived NSCs reverses pathology in the
      brain of a homologous mouse model.
AB  - Neural stem cell (NSC) transplantation is a promising strategy for delivering
      therapeutic proteins in the brain. We evaluated a complete process of ex vivo
      gene therapy using human induced pluripotent stem cell (iPSC)-derived NSC
      transplants in a well-characterized mouse model of a human lysosomal storage
      disease, Sly disease. Human Sly disease fibroblasts were reprogrammed into iPSCs,
      differentiated into a stable and expandable population of NSCs, genetically
      corrected with a transposon vector, and assessed for engraftment in NOD/SCID
      mice. Following neonatal intraventricular transplantation, the NSCs engraft along
      the rostrocaudal axis of the CNS primarily within white matter tracts and survive
      for at least 4 months. Genetically corrected iPSC-NSCs transplanted post
      symptomatically into the striatum of adult Sly disease mice reversed
      neuropathology in a zone surrounding the grafts, while control mock-corrected
      grafts did not. The results demonstrate the potential for ex vivo gene therapy in
      the brain using human NSCs from autologous, non-neural tissues.

PMID- 25866158
TI  - Elimination of tumorigenic human pluripotent stem cells by a recombinant lectin
      toxin fusion protein.
AB  - The application of stem-cell-based therapies in regenerative medicine is hindered
      by the tumorigenic potential of residual human pluripotent stem cells.
      Previously, we identified a human pluripotent stem-cell-specific lectin probe,
      called rBC2LCN, by comprehensive glycome analysis using high-density lectin
      microarrays. Here we developed a recombinant lectin-toxin fusion protein of
      rBC2LCN with a catalytic domain of Pseudomonas aeruginosa exotoxin A, termed
      rBC2LCN-PE23, which could be expressed as a soluble form from the cytoplasm of
      Escherichia coli and purified to homogeneity by one-step affinity chromatography.
      rBC2LCN-PE23 bound to human pluripotent stem cells, followed by its
      internalization, allowing intracellular delivery of a cargo of cytotoxic protein.
      The addition of rBC2LCN-PE23 to the culture medium was sufficient to completely
      eliminate human pluripotent stem cells. Thus, rBC2LCN-PE23 has the potential to
      contribute to the safety of stem-cell-based therapies.

PMID- 25866159
TI  - piggyBac insertional mutagenesis screen identifies a role for nuclear RHOA in
      human ES cell differentiation.
AB  - The mechanisms regulating human embryonic stem (ES) cell self-renewal and
      differentiation are not well defined in part due to the lack of tools for forward
      genetic analysis. We present a piggyBac transposon gain of function screen in
      human ES cells that identifies DENND2C, which genetically cooperates with NANOG
      to maintain self-renewal in the presence of retinoic acid. We show that DENND2C
      negatively regulates RHOA activity, which cooperates with NANOG to block
      differentiation. It has been recently shown that RHOA exists in the nucleus and
      is activated by DNA damage; however, its nuclear function remains unknown. We
      discovered that RHOA associates with DNA and that DENND2C affects nuclear RHOA
      localization, activity, and DNA association. Our study illustrates the power of
      piggyBac as a cost-effective, efficient, and easy to use tool for forward genetic
      screens in human ES cells and provides insight into the role of RHOA in the
      nucleus.

PMID- 25866160
TI  - Human embryonic and induced pluripotent stem cell research trends:
      complementation and diversification of the field.
AB  - Research in human induced pluripotent stem cells (hiPSCs) is rapidly developing
      and there are expectations that this research may obviate the need to use human
      embryonic stem cells (hESCs), the ethics of which has been a subject of
      controversy for more than 15 years. In this study, we investigated approximately
      3,400 original research papers that reported an experimental use of these types
      of human pluripotent stem cells (hPSCs) and were published from 2008 to 2013. We
      found that research into both cell types was conducted independently and further
      expanded, accompanied by a growing intersection of both research fields.
      Moreover, an in-depth analysis of papers that reported the use of both cell types
      indicates that hESCs are still being used as a "gold standard," but in a
      declining proportion of publications. Instead, the expanding research field is
      diversifying and hESC and hiPSC lines are increasingly being used in more
      independent research and application areas. 

PMID- 25866161
TI  - Food consumption of adults in Germany: results of the German National Nutrition
      Survey II based on diet history interviews.
AB  - The second German National Nutrition Survey (NVS II) aimed to evaluate food
      consumption and other aspects of nutritional behaviour of a representative sample
      of the German population, using a modular design with three different dietary
      assessment methods. To assess usual food consumption, 15,371 German speaking
      subjects 14-80 years of age completed a diet history interview between November
      2005 and November 2006. With reference to the guidelines of the German Nutrition
      Society (DGE), NVS II observed that the German population did not eat enough
      foods of plant origin, especially vegetables and consumed too much of meat and
      meat products. While generally similar food consumption is observed in other
      European countries, consumption of bread, fruit juices/nectars and beer is higher
      in Germany. On average, men consumed two times more meat and soft drinks as well
      as six times more beer than women did, whereas the consumption of vegetables,
      fruit as well as herbal/fruit tea was higher in women. Older participants showed
      a lower consumption of meat, fruit juice/nectars, soft drinks and spirits as well
      as a higher consumption of fish, vegetables, fruit, and herbal/fruit tea than
      adolescents and younger adults did. There are also differences in food
      consumption with regard to socio-economic status (SES). Persons with higher SES
      consumed more vegetables, fruit, fish, water, coffee/tea and wine, while persons
      with lower SES consumed more meat and meat products, soft drinks and beer. In
      general, the food consumption of women, the elderly and the higher SES group
      tends to be closer to the official dietary guidelines in Germany.

PMID- 25866163
TI  - Defect-dependent colossal negative thermal expansion in UiO-66(Hf) metal-organic
      framework.
AB  - Thermally-densified hafnium terephthalate UiO-66(Hf) is shown to exhibit the
      strongest isotropic negative thermal expansion (NTE) effect yet reported for a
      metal-organic framework (MOF). Incorporation of correlated vacancy defects within
      the framework affects both the extent of thermal densification and the magnitude
      of NTE observed in the densified product. We thus demonstrate that defect
      inclusion can be used to tune systematically the physical behaviour of a MOF. 

PMID- 25866162
TI  - Heterozygous nonsense mutations near the C-terminal region of IGF1R in two
      patients with small-for-gestational-age-related short stature.
AB  - OBJECTIVE: The type I insulin-like growth factor I receptor (IGF1R) plays an
      important role in growth. We aimed to evaluate the detailed mechanism underlying
      the effect of IGF1R on human growth. PATIENTS AND METHODS: We have performed
      sequence analysis of IGF1R in 55 patients with SGA short stature in Japan, since
      2004, and identified novel heterozygous nonsense mutations in 2 patients: an 8
      year-old Japanese boy (case 1), with a birthweight of 2228 g (-3.3 SDS) and
      height of 46 cm (-2.1 SDS), and a 3-year-old Japanese girl (case 2), with a
      birthweight of 2110 g (-3.0 SDS) and height of 44.3 cm (-2.8 SDS). Both patients
      had a short stature (-3.2 SDS, -3.1 SDS). We determined the protein expression of
      mutated IGF1R, assessed the effect of the endoplasmic reticulum-associated
      degradation (ERAD) pathway on mutated IGF1R, assessed the dominant-negative
      effect of IGF1R and performed quantitative RT-PCR analysis of IGF1R mRNA
      expression in whole blood cells. RESULTS: Two novel heterozygous nonsense
      mutations (case 1: p.Q1250X and case 2: p.W1249X) were identified. Although these
      mutations did not affect blood IGF1R mRNA levels, they significantly decreased
      the expression of IGF1R protein in transiently transfected cells. Treatment with
      the proteasome inhibitor MG132 showed significantly increased IGF1R protein.
      CONCLUSIONS: Heterozygous nonsense mutations affecting the C-terminal region
      (p.Q1250X, p.W1249X) of IGF1R decreased the expression of IGF1R through the ERAD
      pathway. Our study revealed the importance of the C-terminal region and the
      dosage of this receptor for growth.

PMID- 25866165
TI  - The protective effect of male circumcision on HIV infection in a sample of Kenyan
      men.
AB  - This article examines the association between male circumcision and HIV infection
      in a national sample. The analysis is based on the 2003 Kenya Demographic and
      Health Survey (KDHS), a nationally representative household-based population
      survey of adults, in which male respondents self-reported their circumcision
      status. In addition, in some households eligible for individual interview, blood
      samples were subsequently anonymously obtained for HIV testing, making this the
      first study linking socio-demographic information to HIV status at the national
      level. The study sample is limited to 3 413 men aged 15-54 years who gave valid
      information on their circumcision and HIV statuses. Nearly 5% of the men were HIV
      positive, and 86% had been circumcised. HIV prevalence was significantly higher
      among the uncircumcised men (12%) than among the circumcised men (3%). This
      indication of the protective effect of male circumcision on HIV infection
      remained statistically significant (OR 0.15; 95%CI: 0.09-0.23) even after
      controlling for the effects of socio-demographic variables, age at first sexual
      intercourse, and use of paid sex. Based on these results, we recommend that HIV
      prevention advocates and activists, scholars, bio-medical communities and
      political leaders find ways to include this oldest surgical procedure in their
      HIV/AIDS discourses and programmes in sub-Saharan Africa. 

PMID- 25866164
TI  - Personalized health care beyond oncology: new indications for immunoassay-based
      companion diagnostics.
AB  - Personalized health care (PHC) is an evolving field of medicine aimed at
      providing the right therapy to the right patient at the right time. This approach
      often incorporates the use of companion diagnostics (CDx) assays that provide
      information essential for the safe and effective use of the corresponding drug.
      In addition to oncology, many other therapy areas, such as cardiovascular,
      neurological, and infectious and inflammatory diseases, may benefit from PHC,
      owing to disease complexity and heterogeneity. Furthermore, although most U.S.
      Food and Drug Administration-approved CDx are based on molecular-based
      technologies, immunoassays can provide a significant contribution to the
      evolution of CDx in patient management. In this review we discuss how the
      incorporation of biomarker immunoassays into routine diagnostic testing may allow
      early and definitive detection of Alzheimer's disease and enable population
      enrichment in clinical trials. In addition, we will describe how biomarker-based
      CDx immunoassays have potential utility for stratifying patients with asthma
      based on their potential response to therapy and for selecting treatment
      according to phenotypic profile. Continued research into the underlying disease
      pathology and development of accurate and reliable diagnostic assays may ensure
      that PHC becomes the future standard for many indications. 

PMID- 25866166
TI  - HIV/AIDS messages in Malawi and their implications for effective responses.
AB  - This paper explores the nature of HIV/AIDS education and information networks in
      Malawi, with a focus on Dedza district. We consider the role of institutional and
      personal actors involved in Malawi's recently instated and decentralised
      behaviour-change intervention strategy, as well as the form and function of
      interpersonal social networks that mediate this information. The research reveals
      that the organisational capacity of actors and the conflicting messages regarding
      promotion of condom use may prevent Malawi from achieving a coordinated and
      effective decentralised response to the HIV epidemic. The research shows that
      individuals draw on complex interpersonal social networks, often processing mixed
      messages regarding HIV prevention strategies and receiving negative messages
      regarding condom use. The paper discusses the implications of such
      inconsistencies and conflicts with actors, interpersonal social networks and the
      nature of the messages themselves for HIV/AIDS education in Malawi. 

PMID- 25866167
TI  - Responses to VCT for HIV among young people in Kampala, Uganda.
AB  - Attitudes to voluntary counselling and testing (VCT) for HIV among young men and
      women in a slum area of Kampala, Uganda, were studied through 22 individual semi
      structured interviews and 5 focus group discussions. Attitudes to VCT ranged from
      having no problem with the procedure to being very reluctant. Despite fear of
      stigma, the participants perceived 'positive living' after HIV testing as
      realistic. VCT was regarded as an important step to avoid HIV infection, but
      informants expressed the need for the service to be more accessible in terms of
      cost, time and quality of pre- and post-test counselling. We argue that
      counselling without HIV testing should be available for those who are reluctant
      to test. Poverty and gender power imbalances appeared to limit youths'
      possibility of making rational decisions about sexual behaviour and accessing
      VCT. The importance of considering the context in which such issues are being
      negotiated and decided is highlighted. 

PMID- 25866168
TI  - Fertility desire and family-planning demand among HIV-positive women and men
      undergoing antiretroviral treatment in Addis Ababa, Ethiopia.
AB  - Little information exists about desire to have children and family-planning use
      among HIV-positive individuals and how this may vary according to individual,
      social, health and demographic characteristics, especially in developing
      countries. To assess these topics in Ethiopia, a facility-based cross-sectional
      study was undertaken among 460 HIV-positive individuals receiving follow-up care
      at antiretroviral treatment (ART) centres in six public hospitals in Addis Ababa
      in 2006. One hundred and nine of the women (44.7%), 76 of the men (35.2%), and
      40.2% overall of the HIV-positive individuals receiving care desired to have
      children. In comparison to those who said they did not desire to have children,
      those who did desire children tended to be younger (18-29 years) (adjusted odds
      ratio [OR]: 3.05, 95% CI: 1.5-6.4), married or in a relationship (adjusted OR:
      3.4, 95% CI: 2.1-5.6), without a child (adjusted OR: 11.5, 95% CI: 5.3-24.9), and
      with a partner who also desired to have children (adjusted OR: 38.7, 95% CI: 16.7
      89.1). Two hundred and forty-six individuals (53.5%) were using family planning
      (e.g. condoms, abstinence, injectables) and 85 wanted to use family planning in
      the future. The fertility desire and family-planning needs of these ART clients
      have implications for preventing vertical and heterosexual transmission of HIV,
      and the need for appropriate counselling and delivery of services. 

PMID- 25866169
TI  - Competing or co-existing? Representations of HIV/AIDS by white women teachers in
      post-apartheid South Africa.
AB  - This study explores the social representations of HIV and AIDS that circulate
      among white women teachers in South Africa, a group whose personal risk of the
      disease is low but who have a major role to play in shaping attitudes to HIV/AIDS
      among children and young people. The study examines how white women talk about
      the origin and causes of the spread of HIV in South Africa and their personal and
      community risk. This was explored through 25 semi-structured interviews and two
      focus groups with white female teachers in Johannesburg. A thematic analysis of
      the in-depth interviews revealed a shared private understanding of the disease,
      wherein the women distanced themselves by anchoring it in the context of racist
      cultural stereotypes of black sexuality and vulnerability. In contrast, the focus
      group discussions revealed a type of public talk in which HIV/AIDS is anchored in
      the contemporary cultural images of the new South Africa and the spirit of ubuntu
      or togetherness. These contradictory views reflect the racial tensions and social
      contexts of South Africa and which shape HIV/AIDS discourses. The findings
      suggest that more needs to be done to create a genuine understanding of HIV and
      AIDS within contemporary South African contexts. 

PMID- 25866170
TI  - Short-term effects of a peer group intervention for HIV prevention among trainee
      teachers in Malawi.
AB  - This report describes the implementation and short-term results of a peer group
      intervention for HIV prevention on the HIV-related attitudes, knowledge and
      behaviours of primary school teachers in Malawi. The intervention, based on the
      social-cognitive learning model, took place in 2000 at two teacher training
      colleges with a distance-learning programme. Primary school teachers attending a
      final six-week training session before certification volunteered to participate.
      Group leaders were teachers selected by each group, and after training they
      facilitated the peer group intervention. The teachers completed a pre-test and
      post-test questionnaire. The 286 trainee teachers whose pre- and post-test
      samples could be matched, largely reported positive changes in their HIV
      prevention-related knowledge, attitudes, self-efficacy, behaviour change and
      condom-use intentions. However, at post-test immediately after the intervention
      they did not show a higher level of perceived-risk, a greater hope that people
      could change their high-risk sexual behaviour, or greater agreement that persons
      infected with HIV should be allowed in public places. This research demonstrates
      the feasibility of an HIV-prevention intervention for primary school teachers
      during their training. The Malawi Ministry of Education has since made the
      programme available to over 90 per cent of all trainee teachers through an NGO. 

PMID- 25866171
TI  - Boundaries of care: the role of the school in supporting vulnerable children in
      the context of HIV and AIDS.
AB  - This paper is a response to a growing vision of schools as sites of care and
      support for vulnerable children in the context of HIV and AIDS. The aim is to
      interrogate this notion and to raise some key issues in considering the role of
      schools in the context of the epidemic. The paper is based on two research
      activities. The first was a desk review of projects working in the area of
      schools in the context of HIV/AIDS and poverty, including a review of the
      policies underlying these initiatives. The second was the documentation of a
      particular project in a province of South Africa. The paper begins by outlining
      some major education policies in South Africa related to the care and support of
      vulnerable children in the context of HIV and AIDS. The paper then offers three
      cautionary notes in relation to the thrust of these policies and those programmes
      attempting to implement them. The first suggests consideration of the context of
      implementation - the schooling system. The second recommends consideration for
      resourcing these policies, which is looked at through a case study. The third
      note considers the policy visions of schools and teachers: how schools and
      teachers are conceptualised both in policies and programmes is problematised. The
      misalignment between the policies around schools and vulnerable children, the
      resourcing of these policies, and their contexts of implementation is brought
      into relief, as well as the implications for thinking about expanded roles for
      schools and teachers. The paper offers possible ways forward in considering the
      role of schools in the context of HIV and AIDS. These include new ways of
      thinking about resourcing, proper monitoring and evaluation of projects, and a
      focus on quality teaching and learning. 

PMID- 25866172
TI  - Contextual factors associated with treatment-seeking and higher-risk sexual
      behaviour in Botswana among men with symptoms of sexually transmitted infections.
AB  - This study investigates contextual factors associated with treatment-seeking
      behaviour and higher-risk sexual conduct of men symptomatic of sexually
      transmitted infections (STIs) in Botswana. Data were drawn from a randomly
      selected, nationally representative sample of 8 222 men, aged 15-64 years, who
      had reported having symptoms suggestive of an STI during the previous twelve
      months. Higher-risk behaviour continues to sustain the HIV epidemic in Botswana.
      At the heart of Botswana's epidemic lies men's reluctance to seek medical
      treatment, engaging in unprotected sex, and having sex with multiple partners
      while symptomatic of an STI. The odds of engaging in unprotected sex while
      symptomatic of an STI were significantly higher among teenage males and males in
      urban households. For every year's increase in the age difference between
      partners there was a 28% increase in the odds of the male having had unprotected
      sex. Being married and having had more than one sexual partner in the last year
      multiplied the odds of having unprotected sex while symptomatic of an STI by
      three times. The longer an infected man remained with symptoms before seeking
      help, the more likely it was to have unprotected sex while infected and the more
      likely to seek treatment from a traditional healer. Notably, having sought
      medical treatment from hospitals, clinics and health workers, as opposed to
      consulting traditional healers, significantly reduced the odds of having had
      unprotected sex while infected with an STI by 48%. The results indicate the need
      to encourage men to utilise public healthcare services. The public health sector
      in Botswana needs to provide healthcare services that are user-friendly for men.
      Increasing the number of treatment sites may also contribute to preventing onward
      transmission of STIs. Special attention needs to be paid to boys' socialisation
      towards gender norms, and men are to be encouraged to play a responsible role in
      HIV prevention. 

PMID- 25866173
TI  - Key determinants of AIDS impact in Southern sub-Saharan Africa.
AB  - To investigate why Southern sub-Saharan Africa is more severely impacted by HIV
      and AIDS than other parts of sub-Saharan Africa, I conducted a review of the
      literature that assessed viral, host and transmission (societal) factors. This
      narrative review evaluates: 1) viral factors, in particular the aggregation of
      subtype-C HIV infections in Southern sub-Saharan Africa; 2) host factors,
      including unique behaviour patterns, concomitant high prevalence of sexually
      transmitted diseases, circumcision patterns, average age at first marriage and
      immunogenetic determinants; and, 3) transmission and societal factors, including
      levels of poverty, degrees of literacy, migrations of people, extent of political
      corruption, and the usage of contaminated injecting needles in community
      settings. HIV prevalence data and published indices on wealth, fertility, and
      governmental corruption were correlated using statistical software. The high
      prevalence of HIV in Southern sub-Saharan Africa is not explained by the unusual
      prevalence of subtype-C HIV infection. Many host factors contribute to HIV
      prevalence, including frequency of genital ulcerating sexually transmitted
      infections, absence of circumcision (compiled odds ratios suggest a protective
      effect of between 40% and 60% from circumcision), and immunogenetic loci, but no
      factor alone explains the high prevalence of HIV in the region. Among
      transmission and societal factors, the wealthiest, most literate and most
      educated, but also the most income-disparate, nations of sub-Saharan Africa show
      the highest HIV prevalence. HIV prevalence is also highest within societies
      experiencing significant migration and conflict as well as in those with
      government systems experiencing a high degree of corruption. The interactions
      between poverty and HIV transmission are complex. Epidemiologic studies currently
      do not suggest a strong role for the community usage of contaminated injecting
      needles. Areas meriting additional study include clade type, host immunogenetic
      determinants, the complex interrelationship of HIV with poverty, and the
      community usage of contaminated injecting needles. 

PMID- 25866174
TI  - Vulnerability to HIV infection among Luo female adolescent orphans in Western
      Kenya.
AB  - Large-scale surveys have reported that about 55% of orphans worldwide are
      adolescents. In Kenya, the majority of HIV-infected adolescents are females. The
      current study used the anthropological methods of in-depth case studies to
      analyse how migratory life situations of individual female adolescent orphans in
      the Luo community of Western Kenya may increase their exposure to HIV. The study
      shows that the ability of the female adolescent orphans to adopt risk-preventive
      behaviour in relation to HIV is determined by a range of factors beyond their
      control of individual sexual behaviour. Although analysis of a single case study
      limits generalisation of the findings, the results provide insights into the
      reason for sex differentials in HIV infection rates among adolescents as reported
      in some large-scale surveys. The paper recommends that HIV prevention strategies
      for adolescents should examine the specific life situations of female orphans by
      focusing on the impacts of HIV and AIDS and poverty on the protective role of the
      family. It also recommends that keeping female adolescent orphans in school or in
      vocational training can be an effective HIV prevention strategy for them. 

PMID- 25866175
TI  - Young Malawians on the interaction between mental health and HIV/AIDS.
AB  - Previous research has identified high levels of mental health problems among
      people affected by HIV. This study surveys specifically adolescents in southern
      Malawi on their experience of the impacts of living with HIV or AIDS on one's
      mental health. At the same time, the study explores the link between mental
      health problems and subsequent HIV-risk behaviour. Short texts relating everyday
      scenarios that depicted symptoms of three mental health problems (i.e.depression,
      anxiety and HIV-related brain impairment) formed the basis of in-depth
      discussions in 12 existing groups of secondary school students, orphans and
      vulnerable children, teenage mothers, and out-of-school youths, in both rural and
      urban settings. The responses show that these young people recognised the mental
      health sequelae of HIV/AIDS as impacting upon many aspects of one's life. The
      young people traced these 'interruptions' and 'disruptions' through deteriorating
      psychological and socio-economic conditions. They showed awareness of a two-way
      interaction between HIV/AIDS and mental illness, indicating that the latter can
      increase thoughts of suicide and HIV risk-taking behaviour. More importantly,
      they identified a number of locally derived community interventions, which if
      supported by statutory health and education services, can significantly
      ameliorate their situations. The findings provide avenues for practical
      integration of mental health provision within HIV prevention, education and care
      initiatives. 

PMID- 25866176
TI  - Community-based care of children with HIV in Potchefstroom, South Africa.
AB  - Children contract HIV infection largely through vertical transmission and are
      vulnerable to AIDS illness due to an immature immune system. In South Africa,
      hospitals are often overburdened and thus children with HIV may be directed to
      the community for care. As a result, non-professional caregivers are a
      predominant source of care for children living with HIV. Various authors,
      including the Department of Health, have stipulated the importance of
      establishing the knowledge and needs of non-professional caregivers of children
      with HIV. Our research has investigated the extent of non-professional
      caregivers' knowledge and needs, specifically those within the Potchefstroom
      district of the North-West Province. The objectives included formulating
      guidelines for a training programme that can enhance relevant knowledge and
      skills among these caregivers. Quantitative data were gathered using a
      questionnaire, which was developed following a literature study. The 109 non
      professional caregivers who responded to the questionnaire displayed some
      knowledge and skills concerning specifically the care of children with HIV or
      AIDS, although gaps existed concerning their knowledge of community-based
      referral, caring needs specific to children, and precautionary measures to
      prevent HIV transmission. Recommendations are made with specific reference to a
      training programme. We surmise that non-professional caregivers play a pivotal
      role in the care of children with HIV in the Potchefstroom district - a service
      that is sometimes rendered in perilous conditions. This study improves our
      understanding of the support and training needed for non-professional caregivers
      in their pursuit to care for children with HIV in resource-limited communities,
      and thus it contributes to the field of nursing science. The findings may
      generate ideas for future research on this important topic. 

PMID- 25866177
TI  - The dermatology life quality index as a means to assess life quality in patients
      with different scar types.
AB  - BACKGROUND: Measuring quality of life through questionnaires is a common method
      to evaluate the impact of different afflictions on the patient's well-being,
      especially in the field of dermatology where appearance changing afflictions are
      common. OBJECTIVES: A variety of questionnaires has been used to distinguish
      different skin conditions like psoriasis, atopic dermatitis and scars. Using the
      Dermatology Life Quality Index (DLQI), we investigated different scar types
      regarding their impact on quality of life. METHODS: We assessed the quality of
      life in 130 patients presenting to our outpatient scar clinic for the first time
      using the DLQI. Scars were analysed according to their clinical appearance
      (physiological scars, keloids, hypertrophic scars, atrophic scars, self-harm
      scars). Physiological scars were established as a baseline for further comparison
      between groups. RESULTS: Patients in the physiological scar group scored a mean
      DLQI score of 2.07 +/- 3.56, patients in the keloid-, hypertrophic scar-,
      atrophic scar- and self-harm scar group scored values of 6.06 +/- 4.00, 2.53 +/-
      2.48, 7.26 +/- 6.72 and 12.00 +/- 3.85 respectively. When compared to the
      baseline group the difference in the overall score for keloids was +3.99 (P <
      0.001), hypertrophic scars scored +0.45 (ns), atrophic scars +5.19 (P < 0.01) and
      self-harm scars +9.93 (P < 0.001). CONCLUSION: Using the DLQI, we could
      demonstrate that different subsets of pathological scars do affect patients in a
      different magnitude. The DLQI provides a promising adjunct for quantifying the
      quality of life in patients suffering from keloids, atrophic- and self-harm scars
      and may constitute an interesting additional tool for monitoring the progress of
      scar treatments.

PMID- 25866178
TI  - Selection of adenovirus-specific and Epstein-Barr virus-specific T cells with
      major histocompatibility class I streptamers under Good Manufacturing Practice
      (GMP)-compliant conditions.
AB  - BACKGROUND AIMS: Despite antiviral drug therapies, human adenovirus (HAdV),
      cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections still contribute
      substantially to transplant-related death of patients after hematopoietic stem
      cell transplantation. Earlier clinical studies demonstrated successful adoptive
      transfer of magnetically selected CMV-specific T cells via removable, and thus
      Good Manufacturing Practice-compliant, major histocompatibility class I
      streptamers. Thus, the primary focus of the present study was the selection of
      HAdV-streptamer+ T cells, although in three experiments, EBV-streptamer+ T cells
      were also selected. METHODS: Cells from leukaphereses of healthy donors were
      prepared in large (1-6 * 10(9)) and small (25 * 10(6)) cell batches. Whereas the
      larger batch was directly labeled with streptamers to select HAdV- and/or EBV
      specific T cells (large-scale), the smaller batch was used to generate in vitro
      virus-specific T-cell lines before streptamer labeling for streptamer selection
      (small-scale). Isolation of HAdV- and/or EBV-specific T cells was performed with
      the use of the CliniMACS device. RESULTS: The purity of HAdV- and EBV-streptamer+
      T cells among CD3+ cells, obtained from large-scale selection, was up to 6.7% and
      44%, respectively. If HAdV- and EBV-streptamers were applied simultaneously, the
      purity of antigen-specific T cells reached up to 50.7%. A further increase in
      purity reaching up to 98% was achieved by small-scale selection of HAdV-specific
      T cells. All final products fulfilled the microbiological and chemical release
      criteria. Interferon-gamma-response indicating functional activity was seen in 6
      of 9 HAdV and 2 of 3 EBV large-scale selections and in 2 of 3 HAdV small-scale
      selections. CONCLUSIONS: HAdV-streptamers were shown to be clinically feasible
      for few patients after the large-scale approach but for larger patient numbers if
      combined with EBV-streptamers or after the small-scale approach.

PMID- 25866180
TI  - Stimulatory effect of insulin on renal proximal tubule sodium transport is
      preserved in type 2 diabetes with nephropathy.
AB  - Our previous study indicates that hyperinsulinemia in metabolic syndrome in the
      absence of nephropathy may promote hypertension by stimulating renal proximal
      tubule (PT) sodium transport via insulin receptor substrate (IRS)
      2/phosphoinositide 3-kinase pathway. In the present study we showed that the
      stimulatory effect of insulin on the Na(+)-HCO3(-) cotransporter NBCe1 in
      isolated PTs was completely preserved in type 2 diabetic rats with overt
      nephropathy. Furthermore, the IRS2 expression and insulin-induced Akt
      phosphorylation in kidney cortex were preserved in these rats. By contrast, the
      IRS1 expression in kidney cortex was markedly reduced, which might be relevant to
      enhanced renal gluconeogenesis consistently reported in diabetes. The stimulatory
      effect of insulin on NBCe1 was preserved also in a human type 2 diabetic patient
      with advanced nephropathy. These results revealed that insulin can stimulate PT
      sodium transport even in type 2 diabetes with overt nephropathy. In addition to
      hypoglycemia, insulin-induced renal sodium retention might also play a role in
      increased cardiovascular risk associated with intensive glycemic control in type
      2 diabetic patients with nephropathy. 

PMID- 25866179
TI  - Sesamin ameliorates lipopolysaccharide/d-galactosamine-induced fulminant hepatic
      failure by suppression of Toll-like receptor 4 signaling in mice.
AB  - Sesamin has been described to exert anti-oxidant and anti-inflammatory
      properties. In present study, we investigated the potential effects and
      mechanisms of sesamin on lipopolysaccharide (LPS)-induced fulminant hepatic
      failure (FHF) in d-galactosamine (D-GalN)-sensitized mice. Our results showed
      that pretreatment with sesamin dose-dependently improved LPS/D-GalN-induced
      mortality and liver injury as indicated by reduced serum levels of
      aminotransferases and alleviated pathological damage as well as hepatocyte
      apoptosis in mice. Additionally, sesamin markedly attenuated LPS/D-GalN-induced
      adhesion molecules expression, and decreased neutrophils recruitment.
      Furthermore, sesamin inhibited LPS-induced tumor necrosis factor-alpha (TNF
      alpha) production, p38 mitogen-activated protein kinases (MAPK) and NF-kappaB
      activation, and Toll like receptor (TLR) 4 expression in mice and in RAW264.7
      macrophage cells. In summary, these results demonstrate that sesamin protects
      mice from LPS-induced FHF and the molecular mechanisms may down-regulate the
      expression of TLR4, block MAPK and NF-kappaB activation, decrease the production
      of TNF-alpha. 

PMID- 25866181
TI  - In vivo characterization of human myofibrillar myopathy genes in zebrafish.
AB  - Myofibrillar myopathies (MFM) are progressive diseases of human heart and
      skeletal muscle with a severe impact on life quality and expectancy of affected
      patients. Although recently several disease genes for myofibrillar myopathies
      could be identified, today most genetic causes and particularly the associated
      mechanisms and signaling events that lead from the mutation to the disease
      phenotype are still mostly unknown. To assess whether the zebrafish is a suitable
      model system to validate MFM candidate genes using targeted antisense-mediated
      knock-down strategies, we here specifically inactivated known human MFM disease
      genes and evaluated the resulting muscular and cardiac phenotypes functionally
      and structurally. Consistently, targeted ablation of MFM genes in zebrafish led
      to compromised skeletal muscle function mostly due to myofibrillar degeneration
      as well as severe heart failure. Similar to what was shown in MFM patients, MFM
      gene-deficient zebrafish showed pronounced gene-specific phenotypic and
      structural differences. In summary, our results indicate that the zebrafish is a
      suitable model to functionally and structurally evaluate novel MFM disease genes
      in vivo. 

PMID- 25866182
TI  - Annexin-A1 controls an ERK-RhoA-NFkappaB activation loop in breast cancer cells.
AB  - Wound healing is critical for normal development and pathological processes
      including cancer cell metastasis. MAPK, Rho-GTPases and NFkappaB are important
      regulators of wound healing, but mechanisms for their integration are
      incompletely understood. Annexin-A1 (ANXA1) is upregulated in invasive breast
      cancer cells resulting in constitutive activation of NFkappaB. We show here that
      silencing ANXA1 increases the formation of stress fibers and focal adhesions,
      which may inhibit wound healing. ANXA1 regulated wound healing is dependent on
      the activation of ERK1/2. ANXA1 increases the activation of RhoA, which is
      dependent on ERK activation. Furthermore, active RhoA is important in NF-kappaB
      activation, where constitutively active RhoA potentiates NFkappaB activation,
      while dominant negative RhoA inhibits NFkappaB activation in response to CXCL12
      stimulation and active MEKK plasmids. These findings establish a central role for
      ANXA1 in the cell migration through the activation of NFkappaB, ERK1/2 and RhoA. 

PMID- 25866183
TI  - Identification of stathmin 1 during peri-implantation period in mouse endometrium
      by a proteomics-based analysis.
AB  - In this work we aimed to identify the differentially expressed proteins and their
      potential roles during peri-implantation period through proteomics-based
      approach. Adult healthy female mice were mated naturally with fertile males to
      produce pregnancy. The models of pseudopregnancy, delayed implantation, and
      artificial decidualization were established. The protein profile between pre
      implantation (D1) and implantation (D5) period was compared by two-dimensional
      electrophoresis (2-DE) and identified by mass spectrometry (MS). 2-DE yielded
      comparative images presenting over 500 protein spots in D1 and D5 mouse
      endometrium. 15 proteins were identified, of which stathmin 1, Apo-A1, hnRNP H3,
      transgelin 2 and arginase 1 were validated by western blotting. Stathmin 1
      expression did not change in pseudopregnancy, but activation of implantation, or
      induction of decidualization increased it dramatically. Under non-pregnant
      status, progesterone alone or in combination with17beta-estradiol increased it
      dramatically. Our results clarified the protein profile in mouse endometrium
      during implantation. The specific expression profile of stathmin 1 suggested that
      it should be involved in implantation and serve as a potential regulator of this
      process. These findings may contribute to the better understanding of the
      molecules events during embryo implantation, and subsequently improve the ability
      to treat infertility. 

PMID- 25866184
TI  - Dysfunction of lipid metabolism in lipodystrophic Seipin-deficient mice.
AB  - Congenital generalized lipodystrophy (CGL) is characterized by a complete loss of
      body adipose tissue accompanying dyslipidemia, severe hepatic steatosis and
      insulin resistance. However, the mechanisms of dyslipidemia and hepatic steatosis
      are unclear. Here using the lipodystrophic Seipin-deficient mouse (Seipin(-/-))
      model, we found Seipin(-/-) mice were unable to respond appropriately to a long
      time fasting and developed postprandial hypertriglyceridemia. Impaired very low
      density lipoprotein (VLDL) secretion and enhanced triglyceride-rich lipoproteins
      (TRL) clearance were also observed in our Seipin(-/-) mice. To identify the
      association between upregulation of hepatic LDL receptor and enhanced TRL
      clearance, we crossed Seipin(-/-) mice with Ldlr(-/-) mice to generate Seipin(-/
      )Ldlr(-/-) mice. Seipin(-/-)Ldlr(-/-) mice displayed increased TRL clearance only
      after 24 h-fast rather 6 h-fast. In contrast to Seipin(-/-) mice, Seipin(-/
      )Ldlr(-/-) mice displayed hypertriglyceridemia as observed in human CGL patients.
      Furthermore, in this study, we demonstrated hepatic steatosis in lipodystrophy
      Seipin(-/-) mice is a metabolic adaptation of dysfunctional adipose tissue. This
      study using lipodystrophic model established the importance of adipose tissue in
      energy homeostasis and lipid metabolism. 

PMID- 25866185
TI  - Eukaryotic initiation factor 4AI interacts with NS4A of Dengue virus and plays an
      antiviral role.
AB  - Dengue virus (DENV) is a mosquito-borne flavivirus that causes the most prevalent
      diseases in tropical and subtropical regions. DENV utilizes host factors to
      facilitate its replication, while host cells intend to restrain virus
      replication. NS4A of DENV has been implicated to play a crucial role during viral
      replication. To identify more cellular proteins that are recruited by NS4A, we
      carried out a tandem affinity purification assay. The mass spectrometry data
      revealed that human eukaryotic initiation factor 4AI (eIF4AI) was one of
      potential NS4A-interacting partners. Co-immunoprecipitation data confirmed the
      interaction between NS4A and eIF4AI, and both the N-terminal ATP-binding domain
      and C-terminal helicase domain of eIF4AI were involved in their association.
      Functionally, silencing of eIF4AI by RNAi significantly increased the replication
      level of DENV1, DENV2 and DENV3. And knockdown of eIF4AI markedly attenuated the
      phosphorylation of protein kinase regulated by dsRNA-activated (PKR) and
      eIF2alpha induced by DENV2 infection. Collectively, these data suggested that a
      potential role of NS4A in antagonizing host antiviral defense is by recruiting
      eIF4AI and escaping the translation inhibition mediated by PKR. 

PMID- 25866186
TI  - Dietary soy isoflavones differentially regulate expression of the lipid-metabolic
      genes in different white adipose tissues of the female Bama mini-pigs.
AB  - Soy isoflavones have been shown to affect lipid metabolism, however the
      underlying molecular mechanism(s) have not yet been fully understood. The present
      study, using female Bama mini-pig as a model, examined the effects of soy
      isoflavones on lipid metabolism and involved gene expression in different white
      adipose tissues. Female Bama Xiang mini-pigs of 35 days old were fed a basal diet
      (control, Con), or basal diet supplemented with increasing amounts of soy
      isoflavones (250, 500, or 1250 mg/kg diet) for 120 days. The results showed that
      soy isoflavones did not affect the body weight, but decreased the dorsal
      subcutaneous adipose tissue (DSA) mass and increased the mass of abdominal
      subcutaneous adipose tissue (ASA) and perirenal adipose tissue (PRA). Besides,
      soy isoflavones decreased the expression of lipogenic genes and increased the
      expression of lipolytic genes in DSA, while the opposite effects were observed in
      ASA and PRA. In addition, the expression of lipoprotein lipase was down regulated
      in DSA while up regulated in ASA and PRA by soy isoflavones. Moreover, the
      expression of estrogen receptors (ERs) was up regulated in DSA, and down
      regulated in ASA and PRA by soy isoflavones. Our results suggest that soy
      isoflavones affected the lipid metabolism in white adipose tissues of Bama mini
      pigs in a site-specific manner, which might be mediated through PPARs and ERs
      regulated gene expression. 

PMID- 25866187
TI  - Engineered Microtissues Formed by Schiff Base Crosslinking Restore the
      Chondrogenic Potential of Aged Mesenchymal Stem Cells.
AB  - A universal method for reproducibly directing stem cell differentiation remains a
      major challenge for clinical applications involving cell-based therapies. The
      standard approach for chondrogenic induction by micromass pellet culture is
      highly susceptible to interdonor variability. A novel method for the fabrication
      of condensation-like engineered microtissues (EMTs) that utilizes hydrophilic
      polysaccharides to induce cell aggregation is reported here. Chondrogenesis of
      mesenchymal stem cells (MSCs) in EMTs is significantly enhanced compared to
      micromass pellets made by centrifugation measured by type II collagen gene
      expression, dimethylmethylene blue assay, and histology. MSCs from aged donors
      that fail to differentiate in pellet culture are successfully induced to
      synthesize cartilage-specific matrix in EMTs under identical media conditions.
      Furthermore, the EMT polysaccharides support the loading and release of the
      chondroinduction factor transforming growth factor beta3 (TGF-beta3). TGF-beta
      loaded EMTs (EMT(+TGF) ) facilitate cartilaginous tissue formation during culture
      in media not supplemented with the growth factor. The clinical potential of this
      approach is demonstrated in an explant defect model where EMT(+TGF) from aged
      MSCs synthesize de novo tissue containing sulfated glycosaminoglycans and type II
      collagen in situ. 

PMID- 25866188
TI  - Abeta(1-42) oligomer-induced leakage in an in vitro blood-brain barrier model is
      associated with up-regulation of RAGE and metalloproteinases, and down-regulation
      of tight junction scaffold proteins.
AB  - Accumulating evidence indicates that abnormal deposition of amyloid-beta (Abeta)
      peptide in the brain is responsible for endothelial cell damage and consequently
      leads to blood-brain barrier (BBB) leakage. However, the mechanisms underlying
      BBB disruption are not well described. We employed an monolayer BBB model
      comprising bEnd.3 cell and found that BBB leakage was induced by treatment with
      Abeta(1-42), and the levels of tight junction (TJ) scaffold proteins (ZO-1,
      Claudin-5, and Occludin) were decreased. Through comparisons of the effects of
      the different components of Abeta(1-42), including monomer (Abeta(1-42)-Mono),
      oligomer (Abeta(1-42)-Oligo), and fibril (Abeta(1-42)-Fibril), our data confirmed
      that Abeta(1-42)-Oligo is likely to be the most important damage factor that
      results in TJ damage and BBB leakage in Alzheimer's disease. We found that the
      incubation of bEnd.3 cells with Abeta(1-42) significantly up-regulated the level
      of receptor for advanced glycation end-products (RAGE). Co-incubation of a
      polyclonal antibody to RAGE and Abeta(1-42)-Oligo in bEnd.3 cells blocked RAGE
      suppression of Abeta(1-42)-Oligo-induced alterations in TJ scaffold proteins and
      reversed Abeta(1-42)-Oligo-induced up-regulation of RAGE, matrix
      metalloproteinase (MMP)-2, and MMP-9. Furthermore, we found that these effects
      induced by Abeta(1-42)-Oligo treatment were effectively suppressed by knockdown
      of RAGE using small interfering RNA (siRNA) transfection. We also found that GM
      6001, a broad-spectrum MMP inhibitor, partially reversed the Abeta(1-42)-Oligo
      induced inhibitor effects in bEnd.3 cells. Thus, these results suggested that
      RAGE played an important role in Abeta-induced BBB leakage and alterations of TJ
      scaffold proteins, through a mechanism that involved up-regulation of MMP-2 and
      MMP-9.

PMID- 25866189
TI  - On the role of marginal confounder prevalence - implications for the high
      dimensional propensity score algorithm.
AB  - PURPOSE: The high-dimensional propensity score algorithm attempts to improve
      control of confounding in typical treatment effect studies in
      pharmacoepidemiology and is increasingly being used for the analysis of large
      administrative databases. Within this multi-step variable selection algorithm,
      the marginal prevalence of non-zero covariate values is considered to be an
      indicator for a count variable's potential confounding impact. We investigate the
      role of the marginal prevalence of confounder variables on potentially caused
      bias magnitudes when estimating risk ratios in point exposure studies with binary
      outcomes. METHODS: We apply the law of total probability in conjunction with an
      established bias formula to derive and illustrate relative bias boundaries with
      respect to marginal confounder prevalence. RESULTS: We show that maximum possible
      bias magnitudes can occur at any marginal prevalence level of a binary confounder
      variable. In particular, we demonstrate that, in case of rare or very common
      exposures, low and high prevalent confounder variables can still have large
      confounding impact on estimated risk ratios. CONCLUSIONS: Covariate pre-selection
      by prevalence may lead to sub-optimal confounder sampling within the high
      dimensional propensity score algorithm. While we believe that the high
      dimensional propensity score has important benefits in large-scale
      pharmacoepidemiologic studies, we recommend omitting the prevalence-based
      empirical identification of candidate covariates.

PMID- 25866190
TI  - The roles of nucleolin subcellular localization in cancer.
AB  - Nucleolin (NCL) is one of the most abundant non ribosomal protein of the
      nucleolus where it plays a central role in polymerase I transcription. NCL is
      also found outside of the nucleolus, in the nucleoplasm, cytoplasm as well as on
      the cell membrane. It acts in all cell compartments to control cellular
      homeostasis and therefore each cellular pool of NCL can play a different role in
      cancer development. NCL overexpression and its increased localization at the cell
      membrane is a common feature of several tumor cells. In cancer cells, NCL
      overexpression influences cell survival, proliferation and invasion through its
      action on different cellular pathways. In this review, we describe how the
      multiple functions of NCL that are associated to its multiple cellular
      localization can participate to the development of cancer. 

PMID- 25866191
TI  - Identification of amyloid beta mid-domain fragments in human cerebrospinal fluid.
AB  - Amyloid beta (Abeta) is a peptide derived from processing of the membrane bound
      amyloid precursor protein and is a main constituent in amyloid plaques in
      Alzheimer's disease (AD). The excess Abeta in AD brain may be caused by altered
      Abeta metabolism, including reduced enzymatic degradation. Our previous enzymatic
      study of Abeta degradation revealed that intracellular enzymes produced several
      truncated Abeta mid-domain fragments. We therefore generated an antibody to
      enable identification of these anticipated Abeta species in cerebrospinal fluid
      (CSF). The produced antibody displayed affinity for the Abeta mid-domain region
      and 36 N-terminally truncated Abeta fragments were precipitated from human CSF
      and identified by liquid chromatography - mass spectrometry. 31 peptides were
      truncated from residue 18 up to 23, N-terminal truncation that have not
      previously been identified in CSF. The results show that the complexity of
      amyloid beta peptides circulating in the CSF is greater than previously suggested
      and we also demonstrate that the mid-domain antibody used can serve as an
      additional tool for mapping a more complete Abeta degradation profile. 

PMID- 25866193
TI  - A novel SWCNT-polyoxometalate nanohybrid material as an electrode for
      electrochemical supercapacitors.
AB  - A novel nanohybrid material that combines single-walled carbon nanotubes (SWCNTs)
      with a polyoxometalate (TBA)5[PVMoO40] (TBA-PV2Mo10, TBA: [(CH3(CH2)3)4N](+),
      tetra-n-butyl ammonium) is investigated for the first time as an electrode
      material for supercapacitors (SCs) in this study. The SWCNT-TBA-PV2Mo10 material
      has been prepared by a simple solution method which electrostatically attaches
      anionic [PV2Mo10O40](5-) anions with organic TBA cations on the SWCNTs. The
      electrochemical performance of SWCNT-TBA-PV2Mo10 electrodes is studied in an
      acidic aqueous electrolyte (1 M H2SO4) by galvanostatic charge/discharge and
      cyclic voltammetry. In this SWCNT-TBA-PV2Mo10 nanohybrid material, TBA-PV2Mo10
      provides redox activity while benefiting from the high electrical conductivity
      and high double-layer capacitance of the SWCNTs that improve both energy and
      power density. An assembled SWCNT-TBA-PV2Mo10 symmetric SC exhibits a 39% higher
      specific capacitance as compared to a symmetric SC employing only SWCNTs as
      electrode materials. Furthermore, the SWCNT-TBA-PV2Mo10 SC exhibits excellent
      cycling stability, retaining 95% of its specific capacitance after 6500 cycles. 

PMID- 25866192
TI  - The role of TORC1 in muscle development in Drosophila.
AB  - Myogenesis is an important process during both development and muscle repair.
      Previous studies suggest that mTORC1 plays a role in the formation of mature
      muscle from immature muscle precursor cells. Here we show that gene expression
      for several myogenic transcription factors including Myf5, Myog and Mef2c but not
      MyoD and myosin heavy chain isoforms decrease when C2C12 cells are treated with
      rapamycin, supporting a role for mTORC1 pathway during muscle development. To
      investigate the possibility that mTORC1 can regulate muscle in vivo we ablated
      the essential dTORC1 subunit Raptor in Drosophila melanogaster and found that
      muscle-specific knockdown of Raptor causes flies to be too weak to emerge from
      their pupal cases during eclosion. Using a series of GAL4 drivers we also show
      that muscle-specific Raptor knockdown also causes shortened lifespan, even when
      eclosure is unaffected. Together these results highlight an important role for
      TORC1 in muscle development, integrity and function in both Drosophila and
      mammalian cells. 

PMID- 25866194
TI  - Anti-neural antibody response in patients with post-treatment Lyme disease
      symptoms versus those with myalgic encephalomyelitis/chronic fatigue syndrome.

PMID- 25866195
TI  - Gut microbiota depletion from early adolescence in mice: Implications for brain
      and behaviour.
AB  - BACKGROUND: There is growing appreciation for the importance of bacteria in
      shaping brain development and behaviour. Adolescence and early adulthood are
      crucial developmental periods during which exposure to harmful environmental
      factors can have a permanent impact on brain function. Such environmental factors
      include perturbations of the gut bacteria that may affect gut-brain
      communication, altering the trajectory of brain development, and increasing
      vulnerability to psychiatric disorders. Here we assess the effects of gut
      bacterial depletion from weaning onwards on adult cognitive, social and emotional
      behaviours and markers of gut-brain axis dysfunction in mice. METHODS: Mice were
      treated with a combination of antibiotics from weaning onwards and effects on
      behaviours and potential gut-brain axis neuromodulators (tryptophan, monoamines,
      and neuropeptides) and BDNF expression were assessed in adulthood. RESULTS:
      Antibiotic-treatment depleted and restructured gut microbiota composition of
      caecal contents and decreased spleen weights in adulthood. Depletion of the gut
      microbiota from weaning onwards reduced anxiety, induced cognitive deficits,
      altered dynamics of the tryptophan metabolic pathway, and significantly reduced
      BDNF, oxytocin and vasopressin expression in the adult brain. CONCLUSIONS:
      Microbiota depletion from weaning onwards by means of chronic treatment with
      antibiotics in mice impacts on anxiety and cognitive behaviours as well as key
      neuromodulators of gut-brain communication in a manner that is similar to that
      reported in germ-free mice. This model may represent a more amenable alternative
      for germ-free mice in the assessment of microbiota modulation of behaviour.
      Finally, these data suggest that despite the presence of a normal gut microbiome
      in early postnatal life, reduced abundance and diversity of the gut microbiota
      from weaning influences adult behaviours and key neuromodulators of the
      microbiota-gut-brain axis suggesting that dysregulation of this axis in the post
      weaning period may contribute to the pathogenesis of disorders associated with
      altered anxiety and cognition.

PMID- 25866197
TI  - Gluten-free snacks using plantain-chickpea and maize blend: chemical composition,
      starch digestibility, and predicted glycemic index.
AB  - An increase in celiac consumers has caused an increasing interest to develop good
      quality gluten-free food products with high nutritional value. Snack foods are
      consumed worldwide and have become a normal part of the eating habits of the
      celiac population making them a target to improve their nutritive value.
      Extrusion and deep-frying of unripe plantain, chickpea, and maize flours blends
      produced gluten-free snacks with high dietary fiber contents (13.7-18.2 g/100 g)
      and low predicted glycemic index (28 to 35). The gluten-free snacks presented
      lower fat content (12.7 to 13.6 g/100 g) than those reported in similar
      commercial snacks. The snack with the highest unripe plantain flour showed higher
      slowly digestible starch (11.6 and 13.4 g/100 g) than its counterpart with the
      highest chickpea flour level (6 g/100 g). The overall acceptability of the gluten
      free snacks was similar to that chili-flavored commercial snack. It was possible
      to develop gluten-free snacks with high dietary fiber content and low predicted
      glycemic index with the blend of the 3 flours, and these gluten-free snacks may
      also be useful as an alternative to reduce excess weight and obesity problems in
      the general population and celiac community.

PMID- 25866198
TI  - Iron- or silver-catalyzed oxidative fluorination of cyclopropanols for the
      synthesis of beta-fluoroketones.
AB  - The Fe(III)- or Ag(I)-catalyzed oxidative fluorination of cyclopropanols via
      radical rearrangement is disclosed. This process features a straightforward and
      highly effective protocol for the site-specific synthesis of beta-fluoroketones
      and represents an expedient method for the synthesis of gamma-, delta- and
      epsilon-fluoroketones. Notably, this reaction proceeds at room temperature and
      tolerates a diverse array of cyclopropanols. 

PMID- 25866200
TI  - Different approaches to quantitative structure-retention relationships in the
      prediction of oligonucleotide retention.
AB  - Quantitative structure-retention relationships studies were performed for
      cholesterol and alkylamide stationary phases, which were previously applied in
      the analysis of nucleotides and oligonucleotides. An octadecyl column was also
      tested. Twenty-four oligonucleotides of various sequences and length were chosen;
      next, their structural descriptors were determined with the use of quantum
      mechanics method. The sequence features were related mainly to their surface
      area, hydrophobicity, and the nature of nucleobases. Moreover, for the first time
      models employing experimentally derived descriptors (the sum of retention factor
      for individual nucleotides) were developed in the quantitative structure
      retention relationship studies of these compounds. The retention of
      oligonucleotides for alkylamide and cholesterol stationary phases may be
      effectively predicted with the use of quantitative structure-retention
      relationship models based only on molecularly modeled descriptors, as well as
      with models employing experimentally derived descriptors. Therefore, we recommend
      the first approach, since descriptors may be easily and quickly calculated.
      However, oligonucleotide retention prediction for octadecyl phases gives better
      results, when individual nucleotide retention factors are known and utilized for
      the creation of a mathematical model. 

PMID- 25866201
TI  - Optical anisotropy reveals molecular order in a mouse enthesis.
AB  - Entheses are specialized biological structures that functionally anchor tendons
      to bones. The complexity, mechanical characteristics and properties of the
      entheses, particularly those related to exercise, mechanical load and
      pathologies, have been extensively analyzed; however, the macromolecular
      organization of the enthesis fibers, as assessed by polarization microscopy, has
      not yet been investigated. Morphological and optical anisotropy characteristics,
      such as birefringence, linear dichroism (LD) and differential interference
      contrast (DIC-PLM) properties, are thus analyzed in this study of a healthy adult
      mouse calcaneal tendon-bone enthesis. The molecular and supramolecular order of
      collagen and GAGs was determined for the collagen bundles of this enthesis. Based
      on a birefringence plot pattern as well as on metachromasy and linear dichroism
      after toluidine blue staining at pH 4.0, a similarity between the calcaneal
      tendon-bone enthesis and cartilage during ossification may be assumed. This
      similarity is assumed to favor the adequacy of this enthesis to support a
      compressive load. Considering that the collagen-proteoglycan complexes and the
      enthesis fibers themselves have a chiral nature, these structures could be acting
      via reciprocal signaling with the cellular environment of the enthesis. 

PMID- 25866203
TI  - High catalytic activity of heteropolynuclear cyanide complexes containing cobalt
      and platinum ions: visible-light driven water oxidation.
AB  - A near-stoichiometric amount of O2 was evolved as observed in the visible-light
      irradiation of an aqueous buffer (pH 8) containing [Ru(II) (2,2'-bipyridine)3 ]
      as a photosensitizer, Na2 S2 O8 as a sacrificial electron acceptor, and a
      heteropolynuclear cyanide complex as a water-oxidation catalyst. The
      heteropolynuclear cyanide complexes exhibited higher catalytic activity than a
      polynuclear cyanide complex containing only Co(III) or Pt(IV) ions as C-bound
      metal ions. The origin of the synergistic effect between Co and Pt ions is
      discussed in relation to electronic and local atomic structures of the complexes.

PMID- 25866202
TI  - Aging-associated formaldehyde-induced norepinephrine deficiency contributes to
      age-related memory decline.
AB  - A norepinephrine (NE) deficiency has been observed in aged rats and in patients
      with Alzheimer's disease and is thought to cause cognitive disorder. Which
      endogenous factor induces NE depletion, however, is largely unknown. In this
      study, we investigated the effects of aging-associated formaldehyde (FA) on the
      inactivation of NE in vitro and in vivo, and on memory behaviors in rodents. The
      results showed that age-related DNA demethylation led to hippocampal FA
      accumulation, and when this occurred, the hippocampal NE content was reduced in
      healthy male rats of different ages. Furthermore, biochemical analysis revealed
      that FA rapidly inactivated NE in vitro and that an intrahippocampal injection of
      FA markedly reduced hippocampal NE levels in healthy adult rats. Unexpectedly, an
      injection of FA (at a pathological level) or 6-hydroxydopamine (6-OHDA, a NE
      depletor) can mimic age-related NE deficiency, long-term potentiation (LTP)
      impairments, and spatial memory deficits in healthy adult rats. Conversely, an
      injection of NE reversed age-related deficits in both LTP and memory in aged
      rats. In agreement with the above results, the senescence-accelerated prone 8
      (SAMP8) mice also exhibited a severe deficit in LTP and memory associated with a
      more severe NE deficiency and FA accumulation, when compared with the age
      matched, senescence-resistant 1 (SAMR1) mice. Injection of resveratrol (a natural
      FA scavenger) or NE into SAMP8 mice reversed FA accumulation and NE deficiency
      and restored the magnitude of LTP and memory. Collectively, these findings
      suggest that accumulated FA is a critical endogenous factor for aging-associated
      NE depletion and cognitive decline.

PMID- 25866204
TI  - Synthesis of silver nanoparticle and its application.
AB  - In this work, silver nanoparticles have been synthesized by wet chemical
      technique, green synthesis and microbial methods. Silver nitrate (10(-3)M) was
      used with aqueous extract to produce silver nanoparticles. From the results it
      was observed that the yield of nanoparticles was high in green synthesis. The
      size of the silver nanoparticles was determined from Scanning Electron Microscope
      analysis (SEM). Fourier Transform Infrared spectroscopy (FTIR) was carried out to
      determine the presence of biomolecules in them. Its cytotoxic effect was studied
      in cancerous cell line and normal cell line. MTT assay was done to test its
      optimal concentration and efficacy which gives valuable information for the use
      of silver nanoparticles for future cancer therapy. 

PMID- 25866205
TI  - Influence of mechanical disintegration on the microbial growth of aerobic sludge
      biomass: A comparative study of ultrasonic and shear gap homogenizers by oxygen
      uptake measurements.
AB  - Wastewater treatment plant incorporates physical, chemical and biological
      processes to treat and remove the contaminants. The main drawback of conventional
      activated sludge process is the huge production of excess sludge, which is an
      unavoidable byproduct. The treatment and disposal of excess sludge costs about
      60% of the total operating cost. The ideal way to reduce excess sludge production
      during wastewater treatment is by preventing biomass formation within the aerobic
      treatment train rather than post treatment of the generated sludge. In the
      present investigation two different mechanical devices namely, Ultrasonic and
      Shear Gap homogenizers have been employed to disintegrate the aerobic biomass.
      This study is intended to restrict the multiplication of microbial biomass and at
      the same time degrade the organics present in wastewater by increasing the
      oxidative capacity of microorganisms. The disintegrability on biomass was
      determined by biochemical methods. Degree of inactivation provides the
      information on inability of microorganisms to consume oxygen upon disruption. The
      soluble COD quantifies the extent of release of intra cellular compounds. The
      participation of disintegrated microorganism in wastewater treatment process was
      carried out in two identical respirometeric reactors. The results show that
      Ultrasonic homogenizer is very effective in the disruption of microorganisms
      leading to a maximum microbial growth reduction of 27%. On the other hand, Shear
      gap homogenizer does not favor the sludge growth reduction rather it facilitates
      the growth. This study also shows that for better microbial growth reduction,
      floc size reduction alone is not sufficient but also microbial disruption is
      essential. 

PMID- 25866206
TI  - Optimization, equilibrium, kinetic, thermodynamic and desorption studies on the
      sorption of Cu(II) from an aqueous solution using marine green algae: Halimeda
      gracilis.
AB  - The aptitude of marine green algae Helimeda gracilis for sorption of Cu(II) ions
      from an aqueous solution was studied in batch experiments. The effect of relevant
      parameters such as function of pH, sorbent dosage, agitation speed and contact
      time was evaluated by using Response surface methodology (RSM). A maximum
      percentage removal of Cu (II) by Halimeda gracilis occurs at pH-4.49, sorbent
      dosage-1.98g/L, agitation speed-119.43rpm and contact time-60.21min. Further, the
      sorbent was characterized by using Fourier Transform Infrared Spectroscopy (FTIR)
      and Scanning electron microscope (SEM) analysis. Experimental data were analyzed
      in terms of pseudo-first order, pseudo-second order, intraparticle diffusion,
      power function and elovich kinetic models. The results showed that the sorption
      process of Cu(II) ions followed well pseudo-second order kinetics. The sorption
      data of Cu(II) ions at 308.15K are fitted to Langmuir, Freundlich, Dubinin
      Radushkevich (D-R), Temkin, Sips and Toth isotherms. Sorption of Cu(II) onto
      marine green algae Helimeda gracilis followed the Langmuir and Toth isotherm
      models (R(2)=0.998 and R(2)=0.999) with the maximum sorption capacity of 38.46
      and 38.07mg/g. The calculated thermodynamic parameters such as DeltaG degrees ,
      DeltaH degrees  and DeltaS degrees  showed that the sorption of Cu(II) ions onto
      Helimeda gracilis biomass was feasible, spontaneous and endothermic. Desorption
      study shows that the sorbent could be regenerated using 0.2M HCl solution, with
      up to 89% recovery. 

PMID- 25866207
TI  - Gestational weight gain in obese women by class of obesity and select
      maternal/newborn outcomes: A systematic review.
AB  - BACKGROUND: Obesity and gestational weight gain impact maternal and fetal risks.
      Gestational weight gain guidelines are not stratified by severity of obesity.
      AIM: Conduct a systematic review of original research with sufficient information
      about gestational weight gain in obese women stratified by obesity class that
      could be compared to current Institute of Medicine guidelines. Evaluate variance
      in risk for selected outcomes of pregnancy with differing gestational weight gain
      in obese women by class of obesity. METHODS: A keyword advanced search was
      conducted of English-language, peer-reviewed journal articles using 3 electronic
      databases, article reference lists and table of content notifications through
      January 2015. Data were synthesized to show changes in risk by prevalence.
      FINDINGS: Ten articles met inclusion criteria. Outcomes assessed were large for
      gestational age, small for gestational age, and cesarean delivery. Results
      represent nearly 740,000 obese women from four different countries. Findings
      consistently demonstrated gestational weight gain varies by obesity class and
      most obese women gain more than recommended by Institute of Medicine guidelines.
      Obese women are at low risk for small for gestational age and high risk for large
      for gestational age and risk varies with class of obesity and gestational weight
      gain. Research suggests the lowest combined risk of selected outcomes with weight
      gain of 5-9kg in women with class I obesity, 1 to less than 5kg for class II
      obesity and no gestational weight gain for women with class III obesity.
      CONCLUSIONS: Gestational weight gain guidelines may need modification for
      severity of obesity.

PMID- 25866208
TI  - Structures of the Ets Protein DNA-binding Domains of Transcription Factors Etv1,
      Etv4, Etv5, and Fev: DETERMINANTS OF DNA BINDING AND REDOX REGULATION BY
      DISULFIDE BOND FORMATION.
AB  - Ets transcription factors, which share the conserved Ets DNA-binding domain,
      number nearly 30 members in humans and are particularly involved in developmental
      processes. Their deregulation following changes in expression, transcriptional
      activity, or by chromosomal translocation plays a critical role in
      carcinogenesis. Ets DNA binding, selectivity, and regulation have been
      extensively studied; however, questions still arise regarding binding specificity
      outside the core GGA recognition sequence and the mode of action of Ets post
      translational modifications. Here, we report the crystal structures of Etv1,
      Etv4, Etv5, and Fev, alone and in complex with DNA. We identify previously
      unrecognized features of the protein-DNA interface. Interactions with the DNA
      backbone account for most of the binding affinity. We describe a highly
      coordinated network of water molecules acting in base selection upstream of the
      GGAA core and the structural features that may account for discrimination against
      methylated cytidine residues. Unexpectedly, all proteins crystallized as
      disulfide-linked dimers, exhibiting a novel interface (distant to the DNA
      recognition helix). Homodimers of Etv1, Etv4, and Etv5 could be reduced to
      monomers, leading to a 40-200-fold increase in DNA binding affinity. Hence, we
      present the first indication of a redox-dependent regulatory mechanism that may
      control the activity of this subset of oncogenic Ets transcription factors. 

PMID- 25866210
TI  - Polyubiquitin Drives the Molecular Interactions of the NF-kappaB Essential
      Modulator (NEMO) by Allosteric Regulation.
AB  - The NF-kappaB essential modulator (NEMO) is the master regulator of NF-kappaB
      signaling, controlling the immune and nervous systems. NEMO affects the activity
      of IkappaB kinase-beta (IKKbeta), which relieves the inhibition of the NF-kappaB
      transcriptional regulation machinery. Despite major effort, there is only a very
      sparse, phenomenological understanding of how NEMO regulates IKKbeta and shows
      specificity in its large range of molecular interactions. We explore the key
      molecular interactions of NEMO using a molecular biophysics approach,
      incorporating rapid-mixing stopped-flow, high-pressure, and CD spectroscopies.
      Our study demonstrates that NEMO has a significant degree of native structural
      disorder and that molecular flexibility and ligand-induced conformational change
      are at the heart of the molecular interactions of NEMO. We found that long chain
      length, unanchored, linear polyubiquitin drives NEMO activity, enhancing the
      affinity of NEMO for IKKbeta and the kinase substrate IkappaBalpha and promoting
      membrane association. We present evidence that unanchored polyubiquitin achieves
      this regulation by inducing NEMO conformational change by an allosteric
      mechanism. We combine our quantitative findings to give a detailed molecular
      mechanistic model for the activity of NEMO, providing insight into the molecular
      mechanism of NEMO activity with broad implications for the biological role of
      free polyubiquitin. 

PMID- 25866211
TI  - Recent genetic discoveries in osteoporosis, sarcopenia and obesity.
AB  - Osteoporosis is a skeletal disorder characterized by low bone mineral density
      (BMD) and an increased susceptibility to fractures. Evidence from genetic studies
      indicates that BMD, a complex quantitative trait with a normal distribution, is
      genetically controlled. Genome-wide association studies (GWAS) as well as studies
      using candidate gene approaches have identified single-nucleotide polymorphisms
      (SNPs) that are associated with BMD, osteoporosis and osteoporotic fractures.
      These SNPs have been mapped close to or within genes including those encoding
      WNT/beta-catenin signaling proteins. Understanding the genetics of osteoporosis
      will help to identify novel candidates for diagnostic and therapeutic targets.
      Genetic factors are also important for the development of sarcopenia, which is
      characterized by a loss of lean body mass, and obesity, which is characterized by
      high fat mass. Hence, in this review, we discuss the genetic factors, identified
      by genetic studies, which regulate the body components related to osteoporosis,
      sarcopenia, and obesity. 

PMID- 25866209
TI  - Peptidylprolyl Isomerase Pin1 Directly Enhances the DNA Binding Functions of
      Estrogen Receptor alpha.
AB  - The transcriptional activity of estrogen receptor alpha (ERalpha), the key driver
      of breast cancer proliferation, is enhanced by multiple cellular interactions,
      including phosphorylation-dependent interaction with Pin1, a proline isomerase,
      which mediates cis-trans isomerization of the N-terminal Ser(P)(118)-Pro(119) in
      the intrinsically disordered AF1 (activation function 1) domain of ERalpha.
      Because both ERalpha and Pin1 have multiple cellular partners, it is unclear how
      Pin1 assists in the regulation of ERalpha transactivation mechanisms and whether
      the functional effects of Pin1 on ERalpha signaling are direct or indirect. Here,
      we tested the specific action of Pin1 on an essential step in ERalpha
      transactivation, binding to specific DNA sites. DNA binding analysis demonstrates
      that stable overexpression of Pin1 increases endogenous ERalpha DNA binding
      activity when activated by estrogen but not by tamoxifen or EGF. Increased DNA
      binding affinity is a direct effect of Pin1 on ERalpha because it is observed in
      solution-based assays with purified components. Further, our data indicate that
      isomerization is required for Pin1-modulation of ERalpha-DNA interactions. In an
      unbiased in vitro DNA binding microarray with hundreds of thousands of
      permutations of ERalpha-binding elements, Pin1 selectively enhances the binding
      affinity of ERalpha to consensus DNA elements. These studies reveal that Pin1
      isomerization of phosphorylated ERalpha can directly regulate the function of the
      adjacent DNA binding domain, and this interaction is further modulated by ligand
      binding in the ligand-binding domain, providing evidence for Pin1-dependent
      allosteric regulation of ERalpha function. 

PMID- 25866212
TI  - Risk prediction in the community: A systematic review of case-finding instruments
      that predict adverse healthcare outcomes in community-dwelling older adults.
AB  - Few case-finding instruments are available to community healthcare professionals.
      This review aims to identify short, valid instruments that detect older community
      dwellers risk of four adverse outcomes: hospitalisation, functional-decline,
      institutionalisation and death. Data sources included PubMed and the Cochrane
      library. Data on outcome measures, patient and instrument characteristics, and
      trial quality (using the Quality In Prognosis Studies [QUIPS] tool), were double
      extracted for derivation-validation studies in community-dwelling older adults
      (>50 years). Forty-six publications, representing 23 unique instruments, were
      included. Only five were externally validated. Mean patient age range was 64.2
      84.6 years. Most instruments n=18, (78%) were derived in North America from
      secondary analysis of survey data. The majority n=12, (52%), measured more than
      one outcome with hospitalisation and the Probability of Repeated Admission score
      the most studied outcome and instrument respectively. All instruments
      incorporated multiple predictors. Activities of daily living n=16, (70%), was
      included most often. Accuracy varied according to instruments and outcomes; area
      under the curve of 0.60-0.73 for hospitalisation, 0.63-0.78 for functional
      decline, 0.70-0.74 for institutionalisation and 0.56-0.82 for death. The QUIPS
      tool showed that 5/23 instruments had low potential for bias across all domains.
      This review highlights the present need to develop short, reliable, valid
      instruments to case-find older adults at risk in the community. 

PMID- 25866213
TI  - Postoperative nausea and vomiting - a narrative review of pathophysiology,
      pharmacotherapy and clinical management strategies.
AB  - INTRODUCTION: Postoperative nausea and vomiting (PONV) are common complications
      concerning patients undergoing general anesthesia. Intensive research was
      performed during the last two decades in order to develop therapeutic and
      prophylactic strategies to prevent this complication. AREAS COVERED: This article
      reviews the pathophysiology as well as pharmacological aspects of PONV
      prophylaxis and treatment. Relevant strategic aspects for pharmacological
      prophylaxis of PONV are discussed and clinical standard operating procedures are
      presented. EXPERT OPINION: The expert opinion focuses on poor implementation of
      actual PONV guidelines and future considerations.

PMID- 25866214
TI  - Complicated Left Ventricular Assist Device Infection Treated With Pump Exchange
      and Left Ventricular Apical Resection.

PMID- 25866215
TI  - Modification of microflora imbalance: future directions for prevention and
      treatment of colorectal cancer?
AB  - Increasing incidence and mortality of colorectal cancer brings the necessity to
      uncover new possibilities in the prevention, diagnosis and treatment. The
      microbiome as the collective genetic material of the microflora, overexceed the
      number of genes in the human genome and is unique for each individual. Due to the
      benefits providing for the host and mainly for immediate interaction with the
      host immune system, a gastrointestinal microflora can be considered "cardinal
      microbiome". Host-microbial relations includes symbiotic, pathogenic and
      competitive interactions. Causal role of gastrointestinal microflora in
      colorectal carcinogenesis is still not well determined. This minireview is
      focused on current evidence in understanding the role of bacteria in colorectal
      carcinogenesis, the impact of bacterial dysbiosis on tumor formation, and ability
      of probiotics and bacterial vectors to modulate the gastrointestinal microflora
      as prevention and therapy tool in colorectal cancer. 

PMID- 25866216
TI  - The impact of Caspase-8 on non-small cell lung cancer brain metastasis in II/III
      stage patient.
AB  - The aim of this study is to evaluate the role of Caspase-8 in predicting non
      small cell lung cancer (NSCLC) metastasis to brain. The expression of Caspase-8
      was analyzed by immunohistochemistry in 203 surgical resected NSCLC patients, who
      were followed up. Caspase-8 expression level was correlated with
      clinicopathological characteristics. Time to brain metastasis (TTBM) was
      estimated using Kaplan-Meier method. Caspase-8 staining was predominantly located
      in the cell cytoplasm of NSCLC. ROC curve achieved a Sensitivity=94.7%,
      Specificity=48.9% and Negative Predictive Value=98.9% in diagnosing high and low
      risk groups to develop brain metastasis (BM). BM was indentified in 16.1%
      (18/112) patients in high Caspase-8 expression group, in contrast, only 1.1%
      (1/91) patients in low level group developed BM. There was a certain relation
      between Caspase-8 level and lymph node metastasis (P=0.08); Caspase-8 expression
      level significantly elevated in high BM risk group (P=0.00). Multivariate
      logistic regression analysis revealed that there was ignificant correlation only
      between Caspase-8 and BM. Univariate and multivariable Cox regression analysis
      demonstrated that only Caspase-8 was the independent variable affecting lung
      cancer BM. Elevated Caspase-8 predicted early metastasis to brain (Log Rank test,
      P=0.00). Our results suggest that elevated Caspase-8 was associated with
      increased incidence of brain metastasis after surgery in NSCLC patients, further
      evaluation of Caspase-8 as a biomarker for identification of patients at high
      risk of brain metastasis is warranted.

PMID- 25866217
TI  - Identification of biomarkers for metastatic osteosarcoma based on DNA microarray
      data.
AB  - Osteosarcoma (OS) is a malignant bone tumor very often with pulmonary metastasis
      and is the main cause of OS mortality. The objective of this study was to screen
      for possible biomarkers of metastatic OS to explore the mechanisms of pulmonary
      metastasis of OS through network construction. GSE14359 was downloaded from the
      Gene Expression Omnibus database, which included 5 samples from conventional OS
      group with 2 replicates and 4 samples from OS pulmonary metastasis group in
      duplicate. Differentially expressed genes (DEGs) between two groups were
      identified by limma packages in R and classical t-test with the threshold of the
      false discovery rate (FDR) <0.05. The Database for Annotation, Visualization and
      Integrated Discovery (DAVID) were then used to perform functional annotation (FDR
      < 0.01). Differential coexpression network was constructed with subspace
      differential coexpression analysis (SDC), and genes with high degrees in the
      differential coexpression network were identified. A total of 1344 genes were
      screened as DEGs, including 677 up- and 667 down-regulated DEGs in the pulmonary
      metastasis of OS. Thirty-one significantly enriched functions were obtained, such
      as blood vessel morphogenesis, defense response, cell death and so on. DEGs with
      high degrees (brain-specific angiogenesis inhibitor 2 (BAI2), formin-like 1
      (FMNL1), dual-specificity phosphatase 7 (DUSP7), transient receptor potential
      melastatin 2 (TRPM2), CBP80/20-dependent translation initiation factor (KIAA0427)
      and C120rf35) in the differential coexpression network were found. BAI2, FMNL1,
      DUSP7 and TRPM2 may be useful markers for predicting tumor metastasis and
      therapeutic targets for the treatment of OS patients with metastasis. 

PMID- 25866218
TI  - Arteriogenic expansion of extratumoral macrovessels - impact of vascular ageing.
AB  - The critical role of the vasculature in cancer progression is predominantly
      studied at the capillary level, and often equated with angiogenesis. However, the
      mechanisms that ensure the supply of increasing blood volume to the expanding
      tumor microcirculation remain presently unclear. Here we used established mouse
      tumor models to document the enlargement (arteriogenesis), of macroscopic feeding
      vessels at considerable distances upstream from the malignant lesion, but not
      contralaterally. These changes are not affected by the procoagulant host tissue
      factor (TF), but are modulated by vascular ageing and atherosclerosis in ApoE-/-
      mice. Moreover, arteriogenic growth involves infiltration of bone marrow derived
      (YFP-labeled) cells and changes the gene expression profiles in the vessel wall.
      Thus, our observations suggest that in addition to local angiogenesis tumors
      influence distant remodeling of regional macroscopic blood vessels in a manner
      that is modulated by certain vascular comorbidities. 

PMID- 25866219
TI  - miR-29b inhibits the progression of esophageal squamous cell carcinoma by
      targeting MMP-2.
AB  - Accumulating evidence has shown that microRNAs (miRNAs) are aberrantly expressed
      in human esophageal cancer and crucial to tumorigenesis. Herein, we identified
      the role of miR-29b in esophageal squamous cell carcinoma (ESCC) development in
      vitro and in vivo. MiR-29b expression was investigated in thirty cases of ESCC
      samples as well as four ESCC cell lines by real-time PCR. Transwell assays were
      conducted to explore the effects of miR-29b on the invasion of human ESCC cell
      lines. The impact of overexpression of miR-29b on putative target MMP-2 were
      subsequently confirmed via Western blot. Our results indicated that MiR-29b
      expression was frequently down-regulated in ESCC specimens and cell lines
      compared with adjacent normal tissues (p<0.05). Overexpression of miR-29b
      suppressed (p<0.05) ESCC cell invasion, as well as the growth of xenograft tumors
      in mice. Overexpression of miR-29b significantly decreased (p<0.05) the protein
      level of MMP-2, which has previously been identified as a direct target of miR
      29b. Thus, our study demonstrated that overexpression of miR-29b inhibits tumor
      growth in part by targeting MMP-2. Our findings revealed that miR-29b may act as
      a tumor suppressor in ESCC, whose dysregulation may be involved in the initiation
      and development of human ESCC. 

PMID- 25866220
TI  - 17-AAG enhances the cytotoxicity of flavopiridol in mantle cell lymphoma via
      autophagy suppression.
AB  - Flavopiridol, a cyclin-dependent kinase inhibitor (CDKI), shows promising anti
      tumor activity in hematologic malignancies. However, Flavopiridol-induced
      protective autophagy may lead to drug resistance. Here we found that Hsp90
      inhibitor 17-AAG can sensitize mantle cell lymphoma (MCL) cells to flavopiridol
      by suppressing flavopiridol-triggered protective autophagy. The suppressing
      effect of 17-AAG on autophgy was mediated by Beclin1 degradation and ERK
      inactivation. Furthermore, 17-AAG enhanced flavopiridol-induced apoptosis and
      growth suppression in MCL cells. Our study may provide some insights into CDKI 
      targeted chemotherapies. 

PMID- 25866221
TI  - Down-regulated long non-coding RNA H19 inhibits carcinogenesis of renal cell
      carcinoma.
AB  - Long non-coding RNAs (lncRNAs) have been shown to have important regulatory roles
      in cancer biology. LncRNA H19 has been recently shown to be upregulated and play
      important roles in several cancers such as breast cancer, bladder cancer, and
      gastric cancer. However, the role of H19 in clear cell renal carcinoma (ccRCC)
      remains largely unknown.The expression levels of lncRNA H19 in ccRCC tissues and
      renal cancer cell lines were evaluated by quantitative Real-time PCR (qRT-PCR).
      And its association with overall survival of patients was analyzed by statistical
      analysis. Small interfering RNA (siRNA) was used to suppress H19 expression in
      renal cancer cell lines. In vitro assays were performed to further explore its
      role in tumor progression.The relative level of H19 was significantly higher in
      ccRCC compared to the adjacent normal renal tissues. And higher expression of H19
      was found in renal cancer cells compared to the nonmalignant renal cells HK-2.
      Furthermore, The ccRCC patients with higher H19 expression had more advanced
      clinical stage and poorer prognosis than those with lower expression, Kaplan
      Meier analysis revealed that patients with higher H19 expression had a poorer
      overall survival and H19 expression could be an independent prognostic marker for
      ccRCC patient. The results of in vitro assays indicated that knockdown of H19
      reduced cell proliferation, invasion, and migration. Our data suggested that
      lncRNA H19 might be considered as a potential prognostic indicator and a target
      for gene therapy of ccRCC. 

PMID- 25866222
TI  - Deltonin induced both apoptosis and autophagy in head and neck squamous carcinoma
      FaDu cell.
AB  - For decades, despite the advancement of medical science, the prognosis of head
      and neck squamous cell carcinoma (HNSCC), has not improved. Deltonin is one of
      the major active components of Dioscorea Zingiberensis Wright that has been used
      for anthrax, rheumatic heart disease, rheumatoid arthritis etc. By employing
      HNSCC FaDu cell and normal human epidermal keratinocyte, we investigate deltonin
      efficacy and associated mechanism in both cell culture and nude mice xenografts.
      Deltonin treatment selectively prevents proliferation of FaDu cells by cell-cycle
      arrest and induction of apoptosis, via activating checkpoint kinase Chk1and Chk2
      as well as caspases 8, 9 and 3. Meanwhile, we found that treatment with deltonin
      induced autophagy, which played a protective role against deltonin-induced
      apoptosis. Further studies revealed that deltonin activated autophagy by Akt-mTOR
      signaling. Additionally, xenograft model showed that administration of deltonin
      significantly inhibited tumor growth and prolonged survival of tumor bearing
      mice. Our studies suggested that deltonin might be a potential chemotherapeutic
      agent against HNSCC, which might contribute to clinical application and
      pharmacological study of deltonin in future anti-cancer research. 

PMID- 25866223
TI  - Involvement of SRPK1 in cisplatin resistance related to long non-coding RNA UCA1
      in human ovarian cancer cells.
AB  - The therapeutic potential of cisplatin in ovarian cancer treatment is restricted
      by the occurrence of cellular resistance. We aimed to explore the role of SRPK1
      in cisplatin resistance related to the long non-coding RNA UCA1 in ovarian cancer
      cell.Totally, 24 ovarian cancer tissues and 16 normal tissues were used to assess
      the expression of UCA1 RNA. UCA1 stable transfected SKOV3 cells were established
      and the ability of cell migration, invasion and cisplatin resistance was
      assessed. The expression of SRPK1 and apoptosis pathway proteins was then
      assessed to explore the mechanism. In addition, SRPK1 knockdown cell line was
      also established and the effects of SRPK1 on cell migration, invasion and
      cisplatin resistance was evaluated.Elevated expression of UCA1 RNA was identified
      in ovarian cancer tissues compared with normal tissues. Expression of UCA1 RNA in
      SKOV3 cells enhanced the cell migration, invasion and cisplatin resistance.
      Increased expression of SRPK1 and anti-apoptosis proteins were found in
      SKOV3/pcDNA-UCA1 cells. Knocking-down SRPK1 could partly rescue the effect of
      UCA1 expression on cell migration, invasion and cisplatin resistance in SKOV3
      cells.Elevated expression of UCA1 RNA was found in ovarian cancer tissues. UCA1
      can improve the cell migration, invasion and induce cisplatin resistance. SRPK1
      and apoptosis pathway proteins may be involved in the effect of UCA1.

PMID- 25866224
TI  - Molecular analysis of EGFR gene in different types of tumor material from NSCLC
      patients.
AB  - Lung carcinoma is the most frequently occurring cancer worldwide and the Non
      small Cell Lung Cancer (NSCLC) subtype represents 80% of all diagnosed cases.
      Epidermal growth factor receptor (EGFR) has an important dual role in NSCLC
      patients. On one hand, EGFR is frequently mutated in many types of tumors, which
      leads to deregulation of important downstream pathways including those affecting
      cell proliferation, differentiation and migration. On the other hand, presence of
      certain activating mutation leads to increased sensitivity of EGFR to tyrosine
      kinase inhibitors (TKIs) treatment. Detection of these mutations is essential for
      identification of NSCLC patients who would profit from such therapy. However, due
      to the nature of available tumor material and the relatively high number of
      mutation hot spots, such DNA analysis may be challenging and time consuming. Here
      we present an approach combining direct sequencing and SNaPshot assay for
      identification of EGFR mutations in FFPE tissues as well as in rarely analyzed
      cytological smears. Using this strategy on the set of 450 tested NSCLC samples;
      we have identified 29 activating mutations and 14 variants, which might be
      interesting in predicting the efficiency of TKI therapy. 

PMID- 25866225
TI  - Evaluation of the SIOPEN semi-quantitative scoring system in planar simpatico
      adrenal MIBG scintigraphy in children with neuroblastoma.
AB  - Neuroblastoma is the most common malignancy in children comprising 7.6% of all
      infantile cancers. MIBG scintigraphy is a mandatory neuroblastoma diagnostic
      test, which is among others methods, semi-quantified by the SIOPEN method. The
      aim of this study was to test both the skeletal and the soft tissue segments of
      the SIOPEN scoring method in the diagnostic milieu and to correlate them with the
      Curie score. Since there is little knowledge of their diagnostic power, the
      following variables were tested: VMA, HVA, LDH, and MYCN, ferritin, bone marrow
      infiltration, the INSS and the INPC classification. The cross-sectional study
      with repeated measurements of 143 scintigrams was performed on 76 pediatric
      patients with suspected or proven neuroblastoma, who had been referred to the
      Center for Nuclear Medicine of the Clinical Center of Serbia in the period 2007
      2012. The range of the SIOPEN soft tissue scores was 0-5. The range of the SIOPEN
      skeletal scores was 0-57. The range of the Curie scores was 0-26. The skeletal
      SIOPEN scores were significantly higher in bone marrow positive children, in
      children with pathologically elevated urinary VMA levels and in children having a
      more advanced clinical stage. There was no difference in the SIOPEN soft tissue
      score due to higher VMA levels, or depending on the clinical stage and positive
      bone marrow assessment. There was no difference between the SIOPEN skeletal and
      soft tissue scores on one hand and the histological grade of the tumor; elevated
      or normal levels of HVA, LDH, NSE and ferritin, or the presence or absence of
      MYNC amplification in the neuroblastoma cell line, on the other hand. The results
      of both SIOPEN scores showed a high linear correlation with the Curie score. The
      conclusion is that the soft tissue segment of the SIOPEN score needs further
      elucidation in a more controlled milieu. Excellent correlation between all
      segments of the two semi-quantitative scoring methods speaks in favor of the
      application of the complete SIOPEN scoring system in every day mIBG scanning. 

PMID- 25866226
TI  - Correlation between carbonic anhydrase IX (CA-9), XII (CA-12) and hypoxia
      inducible factor-2alpha (HIF-2alpha) in breast cancer.
AB  - Hypoxia inducible factor 2alpha (HIF-2alpha) can trigger the expression of
      several genes related to many aspects of tumor progress under hypoxia. As an
      independent factor, the role of HIF-2alpha is different from other hypoxia
      mediated elements, including HIF-1alpha. Carbonic anhydrase (CA) were also
      regarded as important enzymes that involve in the tumor microenvironment pH. To
      find clinical-pathological features of breast cancer in plateau and explore the
      impact of CAIX, XII (CA-9, CA-12) and HIF-2alpha on patients with breast cancer.
      Clinical data were collected and summarized in 94 patients with breast cancer.
      The expression of HIF-2alpha, CA-9 and CA-12 were detected, using
      immunohistochemistry of specimens. The relation between expressions and clinical
      pathology was analyzed. Under normoxia, hypoxia, and after being pretreated with
      the JNK inhibitor SP600125, HIF- 2alpha, CA-9 and CA-12 expressions were
      detected, and adhesion and invasion assays were performed in MCF-7 cells and HIF-
      2alpha shRNA cells, respectively. There are higher expressions of HIF-2alpha in
      tumor classification 2 and clinical stage 2 (P < 0.05). High expression of CA-12
      was observed in clinical stage 2 (P < 0.05). CA-9 expression is significantly
      correlated with CA-12 expression (r = 0.376, P = 0.0001). HIF-2alpha expression
      is not correlated with both CA-9 expression (P = 0.21) and CA-12 expression (P =
      0.27). Breast cancer cells in vitro showed that HIF-2alpha, CA-9 or CA-12 had an
      increase expression under hypoxia (1% O2). CA-9 or CA-12 expression was observed
      in HIF-2alpha shRNA cells. JNK inhibitor SP 600125 reduced the HIF-2alpha
      expression and inhibited the adhesion and invasion of breast cancer cell. Slight
      inhibition effect on CA-9 and CA-12 expression was found. In conclusion, HIF
      2alpha, CA-9 and CA-12 are important hypoxia responsive elements in breast
      cancer. HIF-2alpha was involved in metastasis and invasion of breast cancer cells
      under hypoxia, by the involvement of c-Jun NH2-terminal kinase (JNK) signal
      pathway. CA-9 and CA-12 may tend to be regulated by HIF-1alpha more often than by
      HIF-2alpha under hypoxia. 

PMID- 25866227
TI  - Expression of CDCA8 correlates closely with FOXM1 in breast cancer: public
      microarray data analysis and immunohistochemical study.
AB  - Forkhead Box M1 (FOXM1) is an oncogenic transcription factor implicated in breast
      cancer progression and metastasis. However, the clinical significance of FOXM1
      and its associated signaling genes in human breast cancer still needed to be
      clarified. In this study, we first analyzed the co-expression gene pattern of
      FOXM1 in three breast cancer gene expression microarray datasets from the
      Oncomine database. Cell division cycle associated 8 (CDCA8) gene was identified
      to correlate closely with FOXM1. In silico analysis further indicated that CDCA8
      overexpressed in breast cancer tissues compared with the normal controls is
      significantly associated with the triple-negative phenotype. Experimentally, we
      performed a immunohistochemical study to detect the expression of CDCA8 in 112
      breast cancer samples, and evaluated its clinicopathological and prognostic
      significance. We found that CDCA8 was frequently over-expressed in breast cancer
      tissues, and increased expression of CDCA8 was positively associated with FOXM1
      expression, triple-negative phenotype and shorter overall survival. Moreover, we
      also found that combination of CDCA8 and FOXM1 showed a higher hazard ratio than
      the individual markers. Our results suggest that FOXM1-CDCA8 signature might be
      involved in breast cancer progression, and serves as a potential prognostic
      factor and a promising therapeutical target. 

PMID- 25866228
TI  - Trefoil factor family (TFF) proteins as potential serum biomarkers in patients
      with metastatic colorectal cancer.
AB  - Trefoil factor family (TFF) is composed of three secretory proteins (TFF1, TFF2
      and TFF3) that play an important role in mucosal protection of gastrointestinal
      tract. Their overexpression in colorectal tumors seems to be associated with more
      aggressive disease. We collected serum samples from 79 healthy controls and 97
      patients with metastatic colorectal cancer at the time of diagnosis or at
      progression. Serum levels of TTF1-3, CEA and CA19-9 were measured by ELISA. Serum
      TFF1 and TFF3 levels were significantly higher in patients with colorectal cancer
      compared to healthy controls (p < 0.0001). Moreover, serum levels of TFF3
      correlated with extent of liver involvement in patient without pulmonary
      metastases and patients with higher TFF3 levels had significantly worse outcome
      (p < 0.0001). Compared to CEA and CA19-9, TFF3 had higher sensitivity and the
      same specificity. Our results indicate that TFF3 is an effective biomarker in
      patients with metastatic colorectal cancer with higher sensitivity than CEA a
      CA19-9. TFF3 levels strongly correlate with extension of liver disease and seem
      to have prognostic value. 

PMID- 25866229
TI  - Long-term outcomes and prognostic factors of patients with pulmonary carcinoid
      tumors.
AB  - The aim of the study was to evaluate type of surgery, long-term survival and
      factors influencing outcome of pulmonary carcinoid tumors. We reviewed our
      database of 137 patients surgically treated for typical or atypical carcinoid
      tumors at our department between 1998 and 2013. There were 95 (69%) patients with
      typical carcinoid (87 N0, 6 N1, 2 N2) and 42 (31%) with atypical carcinoid (26
      N0, 8 N1, 8 N2). Patients with atypical carcinoid were older than those with
      typical carcinoid (median age of 57+/-8.1 and 50.5+/-15.8 years, respectively,
      p<0.00001). The resection performed consisted of 6 (4.4%) pneumonectomies, 110
      (80.1%) lobectomies and bilobectomies, 15 (11%) sleeve lobectomies, 2 (1.5%)
      resections of main bronchus and 4 (3%) wedge resections. Overall 5- and 10-year
      survival rates for different tumors were as follows: typical carcinoid: 97.2% and
      89.9%, respectively; atypical carcinoid 71.1% and 62.2%, respectively.
      Statistical analyses indicated that histology (typical carcinoid, p<0.00001), age
      (less than 45 years, p=0.004) and nodal status (N0, p=0.0002) were significant
      prognostic factors for better prognosis. Histological sub-type and nodal
      involvement appear as the most important factors influencing the prognosis.
      Systemic lymphadenectomy is recommended and should always be performed. 

PMID- 25866230
TI  - Prognostic validation of the WHO 2010 grading system in pancreatic insulinoma
      patients.
AB  - The purpose of this study was to evaluate the prognostic potential of the World
      Health Organization (WHO) 2010 grading system in patients with pancreatic
      insulinomas. This was a retrospective study that analyzed the overall survival of
      85 pancreatic insulinoma patients treated at our Institute between May 2002 and
      March 2013. The mean age of our patient cohort was 44.26 +/- 13.82 years, with
      the gender split at 30 males and 55 females. Median survival time of the cohort,
      post-surgery, was 100.23 +/- 18.18 months. Among the 85 patients,
      histopathological analyses revealed 52 Low Grade (G1) neuroendocrine tumors
      (NET), 23 Intermediate Grade (G2) NET, and 10 High Grade (G3) Neuroendocrine
      carcinomas (NEC) according to the WHO 2010 grading classification. Significant
      difference for overall survival was observed between the NET G1 and NEC G3 groups
      (P<0.01), and the NET G2 and NEC G3 groups (P<0.019). In addition, our data
      showed that overall survival was significantly correlated with the European
      Neuroendocrine Tumor Society (ENETS) tumor-node-metastasis (TNM) staging system,
      and in multivariate analysis, the diameter of tumor was found to be significantly
      correlated with survival (P=0.038). These findings provide additional validation
      for the prognostic value of using the WHO 2010 grading system, specifically with
      regard to pancreatic insulinomas. 

PMID- 25866231
TI  - Molecular allergy diagnosis for the clinical characterization of asthma.
AB  - Defining the allergen sensitization of a patient with asthma at the molecular
      level by measuring specific IgE to purified natural or recombinant allergens can
      improve diagnostic accuracy and improve asthma phenotyping. Molecular diagnosis
      is possible thanks to the specificity of some markers of species-specific
      sensitization and resolve cross-reactivity phenomena from a true co
      sensitization. None of this precision is possible with conventional allergy
      tests, and such information will eventually give clinicians the possibility to
      individualize the actions taken, including indications on reducing targeted
      allergen exposure or selection of suitable allergens for specific immunotherapy,
      thereby increasing the safety and efficacy of immunotherapy. Nevertheless, all in
      vitro tests should be assessed alongside clinical history, as allergen
      sensitization does not necessarily imply clinical responsiveness. 

PMID- 25866232
TI  - Introduction of new editor.

PMID- 25866233
TI  - Designing ligand-enhanced optical absorption of thiolated gold nanoclusters.
AB  - The optical spectra of thiolated Au25(SR)18/Au23(SR)16 clusters with different R
      residues are investigated via TDDFT simulations. Significant enhancements in the
      optical region and effective electron delocalization are simultaneously achieved
      by tuning the ligands' steric hindrance and electronic conjugating features,
      producing a resonance phenomenon between the Au-S core motif and the ligand
      fragments. 

PMID- 25866234
TI  - Determining ethyl glucuronide cutoffs when detecting self-reported alcohol use in
      addiction treatment patients.
AB  - BACKGROUND: Ethyl glucuronide (EtG) is an alcohol biomarker with potential
      utility as a clinical research and alcohol treatment outcome. Debate exists
      regarding the appropriate cutoff level for determining alcohol use, particularly
      with the EtG immunoassay. This study determined the EtG immunoassay cutoff levels
      that most closely correspond to self-reported drinking in alcohol-dependent
      outpatients. METHODS: Eighty adults with alcohol dependence and mental illness,
      taking part in an alcohol treatment study, provided urine samples 3 times per
      week for up to 16 weeks (1,589 samples). Self-reported drinking during 120 hours
      prior to each sample collection was assessed. Receiver operating characteristic
      analyses were conducted to assess the ability of the EtG immunoassay to detect
      self-reported alcohol use across 24- to 120-hour time periods. Sensitivity and
      specificity of EtG immunoassay cutoff levels was compared in 100 ng/ml increments
      (100 to 500 ng/ml) across 24 to 120 hours. RESULTS: Over half (57%) of the 1,589
      samples indicated recent alcohol consumption. The EtG immunoassay closely
      corresponded to self-reported drinking from 24 (area under the curve [AUC] =
      0.90, 95% confidence interval [CI]: 0.88, 0.92) to 120 hours (AUC = 0.88, 95% CI:
      0.87, 0.90). When cutoff levels were compared across 24 to 120 hours, 100 ng/ml
      had the highest sensitivity (0.93 to 0.78) and lowest specificity (0.67 to 0.85).
      Relative to 100 ng/ml, the 200 ng/ml cutoff demonstrated a reduction in
      sensitivity (0.89 to 0.67), but improved specificity (0.78 to 0.94). The 300,
      400, and 500 ng/ml cutoffs demonstrated the lowest sensitivity (0.86 to 0.33) and
      highest specificity (0.86 to 0.97) over 24 to 120 hours. CONCLUSIONS: For
      detecting alcohol use for >24 hours, the 200 ng/ml cutoff level is recommended
      for use as a research and clinical outcome.

PMID- 25866236
TI  - The effect of increased classroom ventilation rate indicated by reduced CO2
      concentration on the performance of schoolwork by children.
AB  - The article reports on an experiment which investigated the effect of increased
      classroom ventilation rate on the performance of children aged 10-12 years. The
      experiment was executed at two different schools (two classrooms at each school)
      as a double-blind 2 * 2 crossover intervention where four different performance
      tests were used as surrogates for short-term concentration and logical thinking.
      Only complete pairs of test responses were included in the within-subject
      comparisons of performance, and data were not corrected for learning and fatigue
      effects. Analysis of the total sample suggested the number of correct answers was
      improved significantly in four of four performance test, addition (6.3%), number
      comparison (4.8%), grammatical reasoning (3.2%), and reading and comprehension
      (7.4%), when the outdoor air supply rate was increased from an average of 1.7
      (1.4-2.0) to 6.6 l/s per person. The increased outdoor air supply rate did not
      have any significant effect on the number of errors in any of the performance
      tests. Results from questionnaires regarding pupil perception of the indoor
      environment, reported Sick Building Syndrome symptoms, and motivation suggested
      that the study classroom air was perceived more still and pupil were experiencing
      less pain in the eyes in the recirculation condition compared to the fresh air
      condition.

PMID- 25866235
TI  - Computational Network Model Prediction of Hemodynamic Alterations Due to
      Arteriolar Rarefaction and Estimation of Skeletal Muscle Perfusion in Peripheral
      Arterial Disease.
AB  - OBJECTIVE: To estimate the relative influence of input pressure and arteriole
      rarefaction on gastrocnemius muscle perfusion in patients with PAD after exercise
      and/or percutaneous interventions. METHODS: A computational network model of the
      gastrocnemius muscle microcirculation was adapted to reflect rarefaction based on
      arteriolar density measurements from PAD patients, with and without exercise. A
      normalized input pressure was applied at the feeder artery to simulate both
      reduced and restored ABI in the PAD condition. RESULTS: In simulations of
      arteriolar rarefaction, resistance increased non-linearly with rarefaction,
      leading to a disproportionally large drop in perfusion. In addition, perfusion
      was less sensitive to changes in input pressure as the degree of rarefaction
      increased. Reduced arteriolar density was observed in PAD patients and improved
      33.8% after three months of exercise. In model simulations of PAD, ABI
      restoration yielded perfusion recovery to only 66% of baseline. When exercise
      training was simulated by reducing rarefaction, ABI restoration increased
      perfusion to 80% of baseline. CONCLUSION: Microvascular resistance increases non
      linearly with increasing arteriole rarefaction. Therefore, muscle perfusion
      becomes disproportionally less sensitive to ABI restoration as arteriole
      rarefaction increases. These results highlight the importance of restoring both
      microvascular structure and upstream input pressure in PAD therapy.

PMID- 25866237
TI  - Early readmission in patients hospitalized for ulcerative colitis: incidence and
      risk factors.
AB  - OBJECTIVE: Early readmission rates are becoming an integral measure of the
      quality of care for hospitalized patients with chronic diseases. The incidence
      and predictors of early readmission in patients with inflammatory bowel disease
      (IBD) are uncertain. Risk factors for readmission over the first few weeks may
      differ from those that influence re-hospitalization at later time points. We
      examined the incidence and predictors of both 30-day and 90-day readmissions
      among ulcerative colitis (UC) patients. MATERIALS AND METHODS: A retrospective,
      cohort study was performed including all severe UC patients admitted to a
      tertiary-care hospital between January 2007 and December 2011. All-cause
      readmissions to the medical or surgical service within 30 and 90 days were
      recorded to allow the calculation of early readmission rates. We used multiple
      logistic regression to analyze demographic, hospital-related, general medical and
      IBD-specific factors as potential risk factors for readmission. RESULTS: There
      were a total of 229 patients discharged following hospitalization for severe UC.
      The 30- and 90-day readmission rates were 11.7% and 20.5%, respectively. Forty
      seven percent of early readmissions were for colectomy. In the 30-day analysis,
      only the presence of extensive colitis (odds ratio 3.59; 95% confidence interval
      [CI] 1.41-9.13) compared with left-sided disease was independently associated
      with readmission. Extensive colitis (3.09, 95% CI 1.33-7.08), albumin on
      admission (0.56, 0.31-0.99) and being admitted to a housestaff service (2.87, 95%
      CI 1.14-6.54), were independent predictors of readmission at 90 days.
      CONCLUSIONS: Early readmission is common in IBD. Independent risk factors for
      early readmission included extensive colitis, admission albumin, and being
      admitted to a housestaff service.

PMID- 25866238
TI  - Ethylene vinyl alcohol copolymer (onyx) embolization for acute hemorrhage: a
      systematic review of peripheral applications.
AB  - PURPOSE: To evaluate the endovascular use of ethylene vinyl alcohol (EVOH)
      copolymer (Onyx; ev3 Endovascular, Inc, Plymouth, Minnesota) for the treatment of
      acute peripheral nonneurologic hemorrhage. MATERIALS AND METHODS: MEDLINE and
      PubMed databases were searched for articles published in English from 1946 to
      August 2014 describing patients treated for hemorrhage with EVOH copolymer
      outside of its usual neurovascular applications. Additional cases were collected
      from the bibliographies of relevant articles. Full-text articles were obtained.
      Demographic data, clinical presentation, underlying etiology, culprit vessel,
      endovascular treatment, outcomes, and follow-up times were obtained. RESULTS: The
      literature search yielded 19 relevant articles. Cases of 131 patients (87 men, 44
      women; mean age, 61 y +/- 19.2) describing the treatment of 151 lesions were
      reviewed. The most common categories of arterial lesions were gastrointestinal (n
      = 53) and bronchial (n = 40) in origin. In 14 cases, EVOH copolymer was employed
      after failure or rebleeding following the use of a different embolic agent.
      Average follow-up time was 12.0 months. EVOH copolymer was the sole embolic agent
      used in 105 patients. Rebleeding after treatment with EVOH copolymer occurred in
      10 patients. There were 2 technical failures. One patient died of multiorgan
      failure in the setting of persistent hemoptysis. Complications included 2 nerve
      injuries and 2 minor strokes. CONCLUSIONS: Embolization of acute hemorrhage in
      the peripheral vasculature was safe and effective with EVOH copolymer.

PMID- 25866239
TI  - A national analysis of the complications, cost, and mortality of percutaneous
      lung ablation.
AB  - PURPOSE: To perform a national analysis of the safety and cost of percutaneous
      image-guided lung malignancy ablation. MATERIALS AND METHODS: Using the National
      (Nationwide) Inpatient Sample, we evaluated complications, need for further
      intervention, in-hospital mortality, length of hospitalization, and hospital
      charges for patients undergoing inpatient percutaneous image-guided lung ablation
      in the United States during the period 2007-2011. Additionally, an analysis of
      the relationship between specific patient factors, procedural complications, and
      mortality was performed. RESULTS: The study group consisted of 3,344 patients,
      including 2,072 (61.9%) patients treated for primary lung carcinomas and 1,277
      (38.1%) patients treated for pulmonary metastatic disease. In-hospital mortality
      occurred after 43 (1.3%) ablation procedures. A Charlson comorbidity index score
      >= 4 was associated with higher mortality (odds ratio [OR], 2.84; 95% confidence
      interval [CI], 1.16-6.91). Pneumothorax was the most common complication (38.4%),
      followed by pneumonia (5.7%) and effusion (4.0%). Neither pneumothorax nor chest
      tube insertion was associated with higher in-hospital mortality rates
      (pneumothorax, OR, 1.10; 95% CI, 0.59-2.04, and chest tube insertion, OR, 1.45;
      95% CI, 0.78-2.68). Surgical reintervention via thoracoscopy or thoracotomy
      occurred in 31 cases (0.9%). Median length of hospitalization was 1 day
      (interquartile range, 1-3 d), and median hospital charges were $22,320
      (interquartile range, $13,705-$43,026). CONCLUSIONS: Percutaneous image-guided
      lung ablation of primary and metastatic disease has an acceptable safety profile,
      and surgical reintervention is rarely required. The most frequent complications
      of percutaneous lung ablation were not associated with increased in-hospital
      mortality.

PMID- 25866240
TI  - Design, synthesis, biological evaluation and molecular modeling of
      dihydropyrazole sulfonamide derivatives as potential COX-1/COX-2 inhibitors.
AB  - Novel dihydropyrazole sulfonamide derivatives (30-56) were designed, synthesized,
      and evaluated for their biological activities as COX-1 and COX-2 inhibitors. In
      vitro biological evaluation against three human tumor cell lines revealed that
      most target compounds showed antiproliferative activities. Among the compounds,
      compound 48 exhibited the most potent and selective COX-2 inhibitor (COX-2
      IC50=0.33 MUM; COX-1 IC50=68.49 MUM) relative to the reference drugs celecoxib
      (IC50=0.052 MUM). Docking simulation was performed to position compound 48 into
      the COX-2 active site and the result showed that compound 48 could bind well at
      the COX-2 active site and it indicated that compound 48 could be a potent and
      selective COX-2 inhibitor.

PMID- 25866241
TI  - Fingerprint-based consensus virtual screening towards structurally new 5-HT(6)R
      ligands.
AB  - Virtual screening towards the search of new 5-HT6R ligands was carried out with
      three different fingerprints used for molecules representation. Two structurally
      new compounds were found to be characterized by a significant 5-HT6R activity (Ki
      of 119 and 670 nM). The compounds do not possess a positive ionizable group in
      their structures and therefore they belong to the group of atypical, non-basic 5
      HT6R ligands. The obtained hits were proved to fit well in the 5-HT6R binding
      cavity by docking and molecular dynamic simulation experiments. Moreover, an in
      silico evaluation of the ADMET properties of these compounds predicted their drug
      like character.

PMID- 25866242
TI  - 2-(Isopropylamino)thieno[3,2-d]pyrimidin-4(3H)-one derivatives as selective
      phosphodiesterase 7 inhibitors with potent in vivo efficacy.
AB  - A new series of thienopyrimidinones is synthesized and evaluated as selective
      phosphodiesterase 7 (PDE7) inhibitors for the treatment of inflammatory diseases.
      The modification of the substituents on thienopyrimidinone revealed that an
      isopropylamino group at the 2-position was favorable for aqueous solubility. The
      introduction of 3-pyrrolidines at the 7-position resulted in good solubility,
      highly potent activity, and good PDE7 selectivity. Among the synthesized
      compounds, compound 46 exhibited the greatest inhibition of ear edema in a
      phorbol ester-induced mouse model. 

PMID- 25866243
TI  - Pyridoxal 5 phosphate for neuroleptic-induced tardive dyskinesia.
AB  - BACKGROUND: Tardive dyskinesia is a chronic and disabling abnormal movement
      disorder affecting the muscles of the face, neck, tongue and the limbs. It is a
      common side effect of long-term antipsychotic medication use in individuals with
      schizophrenia and other related psychotic disorders. While there are no known
      effective treatments for tardive dyskinesia to date, some reports suggest that
      pyridoxal 5 phosphate may be effective in reducing the severity of tardive
      dyskinesia symptoms. OBJECTIVES: To determine the effectiveness of pyridoxal 5
      phosphate (vitamin B6 or Pyridoxine or Pyridoxal phosphate) in the treatment of
      neuroleptic-induced tardive dyskinesia among people with schizophrenia and other
      related psychotic disorders. SEARCH METHODS: The Cochrane schizophrenia group's
      register of clinical trials was searched (January 2013) using the phrase:
      [*Pyridoxal* OR *Pyridoxine* OR *P5P* OR *PLP* OR *tardoxal* OR *Vitamin B6* O
      *Vitamin B 6* R in title, abstract or index terms of REFERENCE, or interventions
      of STUDY. References of relevant identified studies were handsearched and where
      necessary, the first authors of relevant studies were contacted. SELECTION
      CRITERIA: Studies described as randomised controlled trials comparing the
      effectiveness pyridoxal 5 phosphate with placebo in the treatment of neuroleptic
      induced tardive dyskinesia among patients with schizophrenia. DATA COLLECTION AND
      ANALYSIS: The review authors independently extracted data from each selected
      study. For dichotomous data, we calculated risk ratios (RR) and their 95%
      confidence intervals (CIs) on an intention-to-treat basis based on a fixed-effect
      model. For continuous data, we calculated mean differences (MD) with 95% CIs,
      again based on a fixed-effect model. We assessed risk of bias for each included
      study and used GRADE (Grading of Recommendations Assessment, Development and
      Evaluation) approach to rate quality of evidence. MAIN RESULTS: Of the 12 records
      retrieved by the search, three trials published in 2001, 2003 and 2007, involving
      80 inpatients with schizophrenia, aged 18 to 71 years, admitted in a psychiatric
      facility and followed up for a period nine weeks to 26 weeks, were included.
      Overall, pyridoxal 5 phosphate produced a significant improvement in tardive
      dyskinesia symptoms when compared with placebo, assessed by a change in
      Extrapyramidal Symptoms Rating Scale (ESRS) scores from baseline to the end of
      the first phase of the included studies (2 RCTs n = 65, RR 19.97, CI 2.87 to
      139.19, low quality evidence). The endpoint tardive dyskinesia score (a measure
      of its severity) assessed with the ESRS, was significantly lower among
      participants on pyridoxal 5 phosphate compared to those on placebo (2 RCTs n =
      60, MD -4.07, CI -6.36 to -1.79, low quality evidence).It was unclear whether
      pyridoxal 5 phosphate led to more side effects (n = 65, 2 RCTs, RR 3.97, CI 0.20
      to 78.59, low quality evidence) or caused deterioration in tardive dyskinesia
      symptoms when compared to placebo (n = 65, 2 RCTs, RR 0.16, CI 0.01 to 3.14, low
      quality evidence). Five participants taking pyridoxal 5 phosphate withdrew from
      the study because they were not willing to take more medications while none of
      the participants taking placebo discontinued their medications (n = 65, 2 RCTs,
      RR 8.72, CI 0.51 to 149.75, low quality evidence).There was no significant
      difference in the endpoint positive and negative psychiatric symptoms scores,
      measured using the Positive and Negative symptoms Scale (PANSS) between
      participants taking pyridoxal 5 phosphate and those taking placebo. For the
      positive symptoms: (n = 15, 1 RCT, MD -1.50, CI -4.80 to 1.80, low quality
      evidence). For negative the symptoms: (n = 15, 1 RCT, MD -1.10, CI -5.92 to 3.72,
      low quality evidence). AUTHORS' CONCLUSIONS: Pyridoxal 5 phosphate may have some
      benefits in reducing the severity of tardive dyskinesia symptoms among
      individuals with schizophrenia. However, the quality of evidence supporting the
      effectiveness of pyridoxal 5 phosphate in treating tardive dyskinesia is low,
      based on few studies, short follow-up periods, small sample sizes and inadequate
      adherence to standardised reporting guidelines for randomised controlled trials
      among the included studies.

PMID- 25866244
TI  - The basal transcription complex component TAF3 transduces changes in nuclear
      phosphoinositides into transcriptional output.
AB  - Phosphoinositides (PI) are important signaling molecules in the nucleus that
      influence gene expression. However, if and how nuclear PI directly affects the
      transcriptional machinery is not known. We report that the lipid kinase PIP4K2B
      regulates nuclear PI5P and the expression of myogenic genes during myoblast
      differentiation. A targeted screen for PI interactors identified the PHD finger
      of TAF3, a TATA box binding protein-associated factor with important roles in
      transcription regulation, pluripotency, and differentiation. We show that the PI
      interaction site is distinct from the known H3K4me3 binding region of TAF3 and
      that PI binding modulates association of TAF3 with H3K4me3 in vitro and with
      chromatin in vivo. Analysis of TAF3 mutants indicates that TAF3 transduces
      PIP4K2B-mediated alterations in PI into changes in specific gene transcription.
      Our study reveals TAF3 as a direct target of nuclear PI and further illustrates
      the importance of basal transcription components as signal transducers.

PMID- 25866245
TI  - PTEN functions by recruitment to cytoplasmic vesicles.
AB  - PTEN is proposed to function at the plasma membrane, where receptor tyrosine
      kinases are activated. However, the majority of PTEN is located throughout the
      cytoplasm. Here, we show that cytoplasmic PTEN is distributed along microtubules,
      tethered to vesicles via phosphatidylinositol 3-phosphate (PI(3)P), the signature
      lipid of endosomes. We demonstrate that the non-catalytic C2 domain of PTEN
      specifically binds PI(3)P through the CBR3 loop. Mutations render this loop
      incapable of PI(3)P binding and abrogate PTEN-mediated inhibition of PI 3
      kinase/AKT signaling. This loss of function is rescued by fusion of the loop
      mutant PTEN to FYVE, the canonical PI(3)P binding domain, demonstrating the
      functional importance of targeting PTEN to endosomal membranes. Beyond revealing
      an upstream activation mechanism of PTEN, our data introduce the concept of PI 3
      kinase signal activation on the vast plasma membrane that is contrasted by PTEN
      mediated signal termination on the small, discrete surfaces of internalized
      vesicles. 

PMID- 25866246
TI  - HOTAIR forms an intricate and modular secondary structure.
AB  - Long noncoding RNAs (lncRNAs) have recently emerged as key players in fundamental
      cellular processes and diseases, but their functions are poorly understood.
      HOTAIR is a 2,148-nt-long lncRNA molecule involved in physiological epidermal
      development and in pathogenic cancer progression, where it has been demonstrated
      to repress tumor and metastasis suppressor genes. To gain insights into the
      molecular mechanisms of HOTAIR, we purified it in a stable and homogenous form in
      vitro, and we determined its functional secondary structure through chemical
      probing and phylogenetic analysis. The HOTAIR structure reveals a degree of
      structural organization comparable to well-folded RNAs, like the group II intron,
      rRNA, or lncRNA steroid receptor activator. It is composed of four independently
      folding modules, two of which correspond to predicted protein-binding domains.
      Secondary structure elements that surround protein-binding motifs are
      evolutionarily conserved. Our work serves as a guide for "navigating" through the
      lncRNA HOTAIR and ultimately for understanding its function. 

PMID- 25866247
TI  - Crystal structures of the E. coli transcription initiation complexes with a
      complete bubble.
AB  - During transcription initiation, RNA polymerase binds to promoter DNA to form an
      initiation complex containing a DNA bubble and enters into abortive cycles of RNA
      synthesis before escaping the promoter to transit into the elongation phase for
      processive RNA synthesis. Here we present the crystal structures of E. coli
      transcription initiation complexes containing a complete transcription bubble and
      de novo synthesized RNA oligonucleotides at about 6-A resolution. The structures
      show how RNA polymerase recognizes DNA promoters that contain spacers of
      different lengths and reveal a bridging interaction between the 5'-triphosphate
      of the nascent RNA and the sigma factor that may function to stabilize the short
      RNA-DNA hybrids during the early stage of transcription initiation. The
      conformation of the RNA oligonucleotides and the paths of the DNA strands in the
      complete initiation complexes provide insights into the mechanism that controls
      both the abortive and productive RNA synthesis.

PMID- 25866250
TI  - Sevalamer Hydrochloride, Sevelamer Carbonate and Lanthanum Carbonate: In Vitro
      and In Vivo Effects on Gastric Environment.
AB  - Hyperphosphatemia is common in patients with chronic renal failure. Phosphate
      binders are associated with gastric intolerance, representing the main reason of
      drug discontinuation. The aim of this study was to compare the effects in vitro
      and in vivo of sevelamer hydrochloride (SH), sevelamer carbonate (SC) and
      lanthanum carbonate (LC) on gastric microenvironment. We have also evaluated the
      efficacy and tolerability of these drugs in hemodialysis (HD) patients. In vitro
      analysis: Dissolution time, ability to uptake phosphorus, changes in pH starting
      from gastric milieu and the amount of carbon dioxide (CO(2)) produced were the
      variables analyzed. In vivo analysis: 24-h esophago-gastric pH measurement was
      evaluated in 24 HD patients treated with phosphate binders and proton pump
      inhibitor (PPI). In vitro: LC dissolved over a longer time compared with SC (58
      +/- 2.4 vs. 12 +/- 0.6 min; P < 0.001) and SH (58 +/- 2.4 vs. 10.3 +/- 0.8 min; P
      < 0.001), determining the most alkaline pH. SC had the highest chelation power,
      binding 4.00 * 10(-9)  mol/L of phosphoric acid. CO2 volume released was
      increased in LC solution (53.2 +/- 7.8) compared to SC (33.9 +/- 6.2; P < 0.001)
      and SH (2.3 +/- 1.8; P < 0.001). In vivo: gastric pH increased after
      administration of phosphate binder. The most alkaline pH was recorded in patients
      treated with SC. The alkalinization of the gastric environment was not prevented
      by PPI therapy. 424 episodes of esophageal reflux were registered, 74% of them
      were alkaline. The LC group was characterized by the highest number of episodes.
      Sevelamer carbonate had a greater capacity and rapidity to chelate phosphorus,
      with a mild tolerability, due to its low CO(2) production. Sevelamer HCl was the
      most tolerated chelator because it did not produce CO(2), while lanthanum
      carbonate was the least soluble.

PMID- 25866249
TI  - Caspase-3 promotes genetic instability and carcinogenesis.
AB  - Apoptosis is typically considered an anti-oncogenic process since caspase
      activation can promote the elimination of genetically unstable or damaged cells.
      We report that a central effector of apoptosis, caspase-3, facilitates rather
      than suppresses chemical- and radiation-induced genetic instability and
      carcinogenesis. We found that a significant fraction of mammalian cells treated
      with ionizing radiation can survive despite caspase-3 activation. Moreover, this
      sublethal activation of caspase-3 promoted persistent DNA damage and oncogenic
      transformation. In addition, chemically induced skin carcinogenesis was
      significantly reduced in mice genetically deficient in caspase-3. Furthermore,
      attenuation of EndoG activity significantly reduced radiation-induced DNA damage
      and oncogenic transformation, identifying EndoG as a downstream effector of
      caspase-3 in this pathway. Our findings suggest that rather than acting as a
      broad inhibitor of carcinogenesis, caspase-3 activation may contribute to genome
      instability and play a pivotal role in tumor formation following damage. 

PMID- 25866248
TI  - Single mammalian cells compensate for differences in cellular volume and DNA copy
      number through independent global transcriptional mechanisms.
AB  - Individual mammalian cells exhibit large variability in cellular volume, even
      with the same absolute DNA content, and so must compensate for differences in DNA
      concentration in order to maintain constant concentration of gene expression
      products. Using single-molecule counting and computational image analysis, we
      show that transcript abundance correlates with cellular volume at the single-cell
      level due to increased global transcription in larger cells. Cell fusion
      experiments establish that increased cellular content itself can directly
      increase transcription. Quantitative analysis shows that this mechanism measures
      the ratio of cellular volume to DNA content, most likely through sequestration of
      a transcriptional factor to DNA. Analysis of transcriptional bursts reveals a
      separate mechanism for gene dosage compensation after DNA replication that
      enables proper transcriptional output during early and late S phase. Our results
      provide a framework for quantitatively understanding the relationships among DNA
      content, cell size, and gene expression variability in single cells. 

PMID- 25866251
TI  - Indications for, and limitations of, the retroangular flap in facial
      reconstruction according to its vascular mapping.
AB  - We have used the retroangular flap for the reconstruction of facial defects after
      excision of tumours. Important variables such as vascular mapping, type of
      anaesthesia, duration of stay in hospital, and the diagnosis and treatment of
      complications were taken into account in assessing its effectiveness. We studied
      187 patients, 103 men and 84 women, who were treated with the retroangular flap,
      and the morphological and cosmetic results analysed. There are many vascular
      variations of the flap The patients were followed up for a median of 12 (range 12
      125) years and their reconstructions were successful. The technique can be
      considered as one of first methods of choice for the reconstruction of cutaneous
      defects of the middle third of the face. 

PMID- 25866252
TI  - Duplicate publications and related problems in published papers on oral and
      maxillofacial surgery.
AB  - As duplicate publication is unethical, our aim was to find out how common it is
      among published papers on oral and maxillofacial surgery. We used PubMed to
      identify index articles published in 2010 in the Journal of Oral and
      Maxillofacial Surgery, the British Journal of Oral and Maxillofacial Surgery, and
      the European Journal of Cranio-Maxillo-Facial Surgery, and searched for possible
      duplicate publications from 2008 to 2012 using the first or second and last
      authors' names. Suspected duplicates were categorised into "non-duplicate" (no
      overlap), "duplicate" (identical results and conclusions), or "salami-sliced"
      publications (part of the index article repeated or continued). Of the 589 index
      articles, 17 (3%) had some form of duplication, but specifically, we found 3
      duplicate, and 15 salami-sliced publications. Most redundant articles originated
      from China (n=4), followed by Italy, Japan, and Germany (3 from each) and the
      United States and Denmark (2 each). Of the 18 redundant publications, 9 did not
      reference the related index article. Duplicate material is still being published,
      and salami-slicing is relatively common among publications on oral and
      maxillofacial surgery. Further research is required into the extent and impact of
      this finding. 

PMID- 25866253
TI  - Intracellular sorting of differently charged chitosan derivatives and chitosan
      based nanoparticles.
AB  - Chitosan (Chi) is a biodegradable nontoxic polycation with multiple reactive
      groups that is easily used to obtain derivatives with a desired charge and
      hydrophobic properties. The aim of this work was to study the intracellular
      traffic of positively charged hexanoyl-chitosan (HC) or HC-based nanoparticles
      (HCNPs) and negatively charged succinoyl-chitosan (SC) and SCNPs in epithelial
      and macrophage cell lines. By using flow cytometry we demonstrated that
      positively charged HC adhered to cell membranes quicker and more efficiently than
      negatively charged SC or NPs. However confocal studies showed that SC and SCNPs
      penetrated cells much more efficiently than HC while HCNPs did not enter the
      epithelial cells. Macrophages also phagocyted better negatively charged material
      but were able to engulf both HC and HCNPs. Upon entering the cells, SC and SCNPs
      were co-localized with endosomes and lysosomes while HC was found in mitochondria
      and, to a lesser extent, in lysosomes of epithelial cells. Macrophages, RAW264.7,
      more efficiently transported all Chi samples to the lysosomal compartment while
      some positively charged material was still found in mitochondria. Incubation of
      Chi derivatives and ChiNPs at pH specific to mitochondria (8.0) and lysosomes
      (4.5) demonstrated the neutralization of Chi charge. We concluded that epithelial
      cells and, to a lesser extent, macrophages sort charged material to the
      organelles neutralizing Chi charge. 

PMID- 25866255
TI  - Effects of oral contraceptive use on the salivary testosterone and cortisol
      responses to training sessions and competitions in elite women athletes.
AB  - This study examined the salivary testosterone (T) and cortisol (C) responses of
      elite women hockey players across 4 activities (light and heavy training, club
      and International competitions). The players formed an oral contraceptive (OC)
      group (n=10) and a Non-OC (n=19) group for analysis. The Non-OC group had higher
      T levels (by 31-52%) across all activities, whilst the OC group showed signs of
      reduced T and C reactivity when data were pooled. As a squad, positive T and C
      changes occurred with heavy training (45%, 46%), club competitions (62%, 80%) and
      International competitions (40%, 27%), respectively. Our results confirm that OC
      use lowers T levels in women athletes whilst reducing the T and C responses to
      training and competition activities within the sporting environment. Differences
      in the physical and/or psychological demands of the sporting activity could be
      contributing factors to the observed hormone responses. These factors require
      consideration when applying theoretical models in sport, with broader
      implications for women around exercising behaviours and stress physiology. 

PMID- 25866254
TI  - SEMA3F prevents metastasis of colorectal cancer by PI3K-AKT-dependent down
      regulation of the ASCL2-CXCR4 axis.
AB  - Semaphorin-3F (SEMA3F), an axonal repulsant in nerve development, has been shown
      to inhibit the progression of human colorectal cancer (CRC); however, the
      underlying mechanism remains elusive. In this study we found a negative
      correlation between the levels of SEMA3F and CXCR4 in CRC specimens from 85
      patients, confirmed by bioinformatics analysis of gene expression in 229 CRC
      samples from the Cancer Genome Atlas. SEMA3F(high) /CXCR4(low) patients showed
      the lowest frequency of lymph node and distant metastasis and the longest
      survival. Mechanistically, SEMA3F inhibited the invasion and metastasis of CRC
      cells through PI3K-AKT-dependent down-regulation of the ASCL2-CXCR4 axis.
      Specifically, ASCL2 enhanced the invasion and metastasis of CRC cells in vitro
      and expression of ASCL2 correlated with distant metastasis, tumour size and poor
      overall survival in CRC patients. Treatment of CRC cells with the CXCR4
      antagonist AMD3100 attenuated SEMA3F knockdown-induced invasion and metastasis of
      CRC cells in vitro and in vivo. Our study thus demonstrates that SEMA3F functions
      as a suppressor of CRC metastasis via down-regulating the ASCL2-CXCR4 axis.

PMID- 25866256
TI  - Effectiveness of High-Frequency Electrical Stimulation Following Sensitization
      With Capsaicin.
AB  - Although nonnoxious, high-frequency electrical stimulation applied segmentally
      (ie, conventional transcutaneous electrical nerve stimulation [TENS]) has been
      proposed to modulate pain, the mechanisms underlying analgesia remain poorly
      understood. To further elucidate how TENS modulates pain, we examined evoked
      responses to noxious thermal stimuli after the induction of sensitization using
      capsaicin in healthy volunteers. We hypothesized that sensitization caused by
      capsaicin application would unmask TENS analgesia, which could not be detected in
      the absence of sensitization. Forty-nine healthy subjects took part in a series
      of experiments. The experiments comprised the application of topical capsaicin
      (.075%) on the left hand in the C6 dermatome, varying the location of TENS
      (segmental, left C6 dermatome, vs extrasegmental, right shoulder), and assessing
      rating of perception (numeric rating scale: 0-10) and evoked potentials to
      noxious contact heat stimuli. The extrasegmental site was included as a control
      condition because previous studies indicate no analgesic effect to remote
      conventional TENS. Conventional TENS had no significant effect on rating or
      sensory evoked potentials in subjects untreated with capsaicin. However,
      segmental TENS applied in conjunction with capsaicin significantly reduced
      sensation to noxious thermal stimuli following a 60-minute period of
      sensitization. PERSPECTIVE: The study indicates that sensitization with capsaicin
      unmasks the analgesic effect of conventional TENS on perception of noxious
      contact heat stimuli. Our findings indicate that TENS may be interacting
      segmentally to modulate distinct aspects of sensitization, which in turn results
      in analgesia to thermal stimulation.

PMID- 25866257
TI  - Gnathodiaphyseal dysplasia presenting as polyostotic fibrous dysplasia.

PMID- 25866258
TI  - Nulliparity is associated with less healthy markers of subclinical cardiovascular
      disease in young women with overweight and obesity.
AB  - OBJECTIVE: Higher parity is associated with increased subclinical cardiovascular
      disease (CVD) in mid-life and older women and with increased CVD risk overall.
      The relationship between parity, subclinical CVD, and infertility in young women
      with overweight and obesity has been infrequently evaluated. METHODS:
      Reproductive histories were obtained in 191 (66%) young women with overweight and
      obesity (BMI 25-39.9 kg/m(2) ) participating in a weight loss trial. Baseline
      carotid intima-media thickness (IMT) and inter-adventitial diameter (IAD) were
      assessed via B-mode ultrasound. Linear regression was used to estimate the
      relationship between parity and carotid measures, adjusted for demographic,
      cardiovascular, and reproductive risk factors. RESULTS: Nulliparous women (n =
      70, age 34.9 +/- 7.1) had increased common carotid IAD (0.230 mm, SE 0.08, P =
      0.003) and mean common carotid artery (CCA) IMT (0.031 mm, SE 0.01, P = 0.007)
      compared with parous women (n = 102, age 39.5 +/- 4.9), persisting after
      adjustment for age, race, and CVD risk factors. No other reproductive factors
      were statistically significantly associated. CONCLUSIONS: Nulliparity is
      associated with markers of less healthy carotid arteries in a sample of disease
      free 25- to 45-year-old women with overweight or obesity. This may represent a
      beneficial effect of pregnancy or indicate overall better health in women with
      overweight/obesity who are capable of childbearing.

PMID- 25866259
TI  - Enhancing hair follicle regeneration by nonablative fractional laser: Assessment
      of irradiation parameters and tissue response.
AB  - BACKGROUND AND OBJECTIVE: Identification of methods to enhance anagen entry can
      be helpful for alopecia. Recently, nonablative laser has been proposed as a
      potential treatment for alopecia. However, how the laser parameters affect stem
      cell activity, hair cycles and the associated side effects have not been well
      characterized. Here we examine the effects of irradiation parameters of 1,550-nm
      fractional laser on hair cycles. STUDY DESIGN/MATERIALS AND METHODS: The dorsal
      skin of eight-week-old female C57BL/6 mice with hair follicles in synchronized
      telogen was shaved and irradiated with a 1,550-nm fractional erbium-glass laser
      (Fraxel RE:STORE (SR1500) Laser System, Solta Medical, U.S.A.) with varied beam
      energies (5-35 mJ) and beam densities (500-3500 microthermal zones/cm(2) ). The
      cutaneous changes were evaluated both grossly and histologically. Hair follicle
      stem cell activity was detected by BrdU incorporation and changes in gene
      expression were quantified by real-time PCR. RESULTS: Direct thermal injury to
      hair follicles could be observed early after irradiation, especially at higher
      beam energy. Anagen induction in the irradiated skin showed an all-or-non change.
      Anagen induction and ulcer formation were affected by the combination of beam
      energy and density. The lowest beam energy of 5 mJ failed to promote anagen entry
      at all beam densities tested. As beam energy increased from 10 mJ to 35 mJ, we
      found a decreasing trend of beam density that could induce anagen entry within 7
      9 days with activation of hair follicle stem cells. Beam density above the pro
      regeneration density could lead to ulcers and scarring followed by anagen entry
      in adjacent skin. Analysis of inflammatory cytokines, including TNF-alpha, IL
      1beta, and IL-6, revealed that transient moderate inflammation was associated
      with anagen induction and intense prolonged inflammation preceded ulcer
      formation. CONCLUSION: To avoid side effects of hair follicle injury and
      scarring, appropriate combination of beam energy and density is required.
      Parameters outside the therapeutic window can result in either no anagen
      promotion or ulcer formation.

PMID- 25866260
TI  - The puzzle of orthostatic tolerance in hereditary sensory and autonomic
      neuropathy, type IV.

PMID- 25866261
TI  - Optical, electrical, and electromechanical properties of hybrid graphene/carbon
      nanotube films.
AB  - By combining a graphene layer and aligned multiwalled carbon nanotube (MWNT)
      sheets in two different configurations, i) graphene on the top of MWNTs and ii)
      MWNTs on the top of the graphene, it is demonstrated that optical, electrical,
      and electromechanical properties of the resulting hybrid films depend on
      configurations. 

PMID- 25866262
TI  - Risk Factors for Adopting Extreme Weight-Control Behaviors among Public School
      Adolescents in Salvador, Brazil: A Case-Control Study.
AB  - OBJECTIVE: This study identifies the risk factors for extreme weight-control
      behaviors among adolescents in public school in Salvador, northeastern Brazil.
      METHODS: A case-control study nested to a cross-sectional study, including 252
      adolescents of both sexes, age between 11 to 17 years, with 84 cases and 168 age
      matched controls was conducted. The variable outcome is represented by extreme
      weight-control behaviors, integrated by following the variables: self-induced
      vomiting and the use of laxatives, diuretics, or diet pills. Covariables included
      body image dissatisfaction, dieting, prolonged fasting, and self-perception of
      body weight. The study also investigated the demographic and anthropometric
      variables and economic conditions of the students' families. Conditional logistic
      regression was used to identify risk factors for the adoption of extreme weight
      control behaviors among adolescents. RESULTS: Among the adolescents investigated,
      the conditional logistic regression explained 22% the occurrence of extreme
      weight-control behaviors and showed that these behaviors were positively
      associated to overweight (odds ratio [OR] = 3.61; 95% confidence interval [CI],
      1.42-9.17), body image dissatisfaction (OR = 3.87; 95% CI, 1.75-8.54), and the
      adoption of a restrictive diet (OR = 2.83; 95% CI, 1.16-6.91). CONCLUSIONS: The
      results of this study suggest that among adolescents, overweight, body image
      dissatisfaction, and restrictive diet are important risk factors to adoption of
      extreme weight-control behaviors.

PMID- 25866263
TI  - BMI and dementia: feast or famine for the brain?

PMID- 25866264
TI  - BMI and risk of dementia in two million people over two decades: a retrospective
      cohort study.
AB  - BACKGROUND: Dementia and obesity are increasingly important public health issues.
      Obesity in middle age has been proposed to lead to dementia in old age. We
      investigated the association between BMI and risk of dementia. METHODS: For this
      retrospective cohort study, we used a cohort of 1,958,191 individuals derived
      from the United Kingdom Clinical Practice Research Datalink (CPRD) which included
      people aged 40 years or older in whom BMI was recorded between 1992 and 2007.
      Follow-up was until the practice's final data collection date, patient death or
      transfer out of practice, or first record of dementia (whichever occurred first).
      People with a previous record of dementia were excluded. We used Poisson
      regression to calculate incidence rates of dementia for each BMI category.
      FINDINGS: Our cohort of 1,958,191 people from UK general practices had a median
      age at baseline of 55 years (IQR 45-66) and a median follow-up of 9.1 years (IQR
      6.3-12.6). Dementia occurred in 45,507 people, at a rate of 2.4 cases per 1000
      person-years. Compared with people of a healthy weight, underweight people (BMI
      <20 kg/m(2)) had a 34% higher (95% CI 29-38) risk of dementia. Furthermore, the
      incidence of dementia continued to fall for every increasing BMI category, with
      very obese people (BMI >40 kg/m(2)) having a 29% lower (95% CI 22-36) dementia
      risk than people of a healthy weight. These patterns persisted throughout two
      decades of follow-up, after adjustment for potential confounders and allowance
      for the J-shape association of BMI with mortality. INTERPRETATION: Being
      underweight in middle age and old age carries an increased risk of dementia over
      two decades. Our results contradict the hypothesis that obesity in middle age
      could increase the risk of dementia in old age. The reasons for and public health
      consequences of these findings need further investigation. FUNDING: None.

PMID- 25866266
TI  - Large piezoelectric response of BiFeO3/BaTiO3 polycrystalline films induced by
      the low-symmetry phase.
AB  - BaTiO3, BiFeO3 and BiFeO3/BaTiO3 polycrystalline films were prepared by the radio
      frequency magnetron sputtering on the Pt/Ti/SiO2/Si substrate. The phase
      structure, converse piezoelectric coefficient and domain structure of BaTiO3,
      BiFeO3 and BiFeO3/BaTiO3 thin films are characterized by XRD and PFM,
      respectively. The converse piezoelectric coefficient d33 of BiFeO3/BaTiO3 thin
      films is 119.5 pm V(-1), which is comparable to that of lead-based piezoelectric
      films. The large piezoelectric response of BiFeO3/BaTiO3 thin films is ascribed
      to the low-symmetry T-like phase BiFeO3, because the spontaneous polarization
      vector of T-like phase (with monoclinic symmetry) BiFeO3 can rotate easily under
      external field. In addition, the reduced leakage current and major domains with
      upward polarization are also attributed to the large piezoelectricity. 

PMID- 25866265
TI  - External guide sequence technology: a path to development of novel antimicrobial
      therapeutics.
AB  - RNase P is a ribozyme originally identified for its role in maturation of tRNAs
      by cleavage of precursor tRNAs (pre-tRNAs) at the 5'-end termini. RNase P is a
      ribonucleoprotein consisting of a catalytic RNA molecule and, depending on the
      organism, one or more cofactor proteins. The site of cleavage of a pre-tRNA is
      identified by its tertiary structure; and any RNA molecule can be cleaved by
      RNase P as long as the RNA forms a duplex that resembles the regional structure
      in the pre-tRNA. When the antisense sequence that forms the duplex with the
      strand that is subsequently cleaved by RNase P is in a separate molecule, it is
      called an external guide sequence (EGS). These fundamental observations are the
      basis for EGS technology, which consists of inhibiting gene expression by
      utilizing an EGS that elicits RNase P-mediated cleavage of a target mRNA
      molecule. EGS technology has been used to inhibit expression of a wide variety of
      genes, and may help development of novel treatments of diseases, including
      multidrug-resistant bacterial and viral infections. 

PMID- 25866269
TI  - Aptamers in targeted nanotherapy.
AB  - The use of aptamers as targeting molecules has revolutionized nanomedicine.
      Aptamers are short oligonucleotides or peptides that can be used as targeting
      ligands against numerous targets. Aptamers are versatile moieties that can be
      used both in therapeutic and targeting applications. Aptamers bind to the target
      in a process that is similar to the lock and key mechanism. There are numerous
      reports on the use of aptamers as targeting moieties for imaging and drug
      delivery applications. In this review, we would like to give a comprehensive
      report on aptamers, its properties and the developments in aptamer mediated drug
      delivery in the recent years. 

PMID- 25866270
TI  - Aptamers overview: selection, features and applications.
AB  - Apatamer technology has been around for a quarter of a century and the field had
      matured enough to start seeing real applications, especially in the medical
      field. Since their discovery, aptamers rapidly emerged as key players in many
      fields, such as diagnostics, drug discovery, food science, drug delivery and
      therapeutics. Because of their synthetic nature, aptamers are evolving at an
      exponential rate gaining from the newest advances in chemistry, nanotechnology,
      biology and medicine. This review is meant to give an overview of the aptamer
      field, by including general aspects of aptamer identification and applications as
      well as highlighting certain features that contribute to their quick deployment
      in the biomedical field. 

PMID- 25866268
TI  - Applications of aptamers in targeted imaging: state of the art.
AB  - Aptamers are single-stranded oligonucleotides with high affinity and specificity
      to the target molecules or cells, thus they can serve as an important category of
      molecular targeting ligand. Since their discovery, aptamers have been rapidly
      translated into clinical practice. The strong target affinity/selectivity, cost
      effectivity, chemical versatility and safety of aptamers are superior to
      traditional peptides- or proteins-based ligands which make them unique choices
      for molecular imaging. Therefore, aptamers are considered to be extremely useful
      to guide various imaging contrast agents to the target tissues or cells for
      optical, magnetic resonance, nuclear, computed tomography, ultrasound and
      multimodality imaging. This review aims to provide an overview of aptamers'
      advantages as targeting ligands and their application in targeted imaging.
      Further research in synthesis of new types of aptamers and their conjugation with
      new categories of contrast agents is required to develop clinically translatable
      aptamer-based imaging agents which will eventually result in improved patient
      care. 

PMID- 25866271
TI  - Aptamer-targeted oligonucleotide theranostics: a smarter approach for brain
      delivery and the treatment of neurological diseases.
AB  - Aptamers represent the novel class of oligonucleotides holding multiple
      applications in the area of biomedicine. The advancements introduced with the
      Systematic Evolution of Ligands by EXponential enrichment (SELEX) approach
      further eased the scope of producing modified aptamers within a short span yet
      retaining the properties of stability and applicability. In the recent times,
      aptamers were identified to have the potential for penetrating into the deep
      human crevices and thus can be utilized in addressing the issues of complex
      neurological disorders. Considering the specificity and stability enhancement by
      chemical modifications, aptamer-based nanotechnologies may have great potential
      for future therapeutics and diagnostics (theranostics). The research community
      has already witnessed success with the approval of macugen (an anti-vascular
      endothelial growth factor aptamer) for treating degenerating eye disease, and
      hopefully those that are in the clinical trials will soon be translated for human
      application. Herein, we have summarized the aptamer chemistry, aptamer
      nanoconjugates and their applications against neurological diseases. 

PMID- 25866267
TI  - Peptide aptamers: development and applications.
AB  - Peptide aptamers are small combinatorial proteins that are selected to bind to
      specific sites on their target molecules. Peptide aptamers consist of short, 5-20
      amino acid residues long sequences, typically embedded as a loop within a stable
      protein scaffold. Various peptide aptamer scaffolds and in vitro and in vivo
      selection techniques are reviewed with emphasis on specific biomedical,
      bioimaging, and bioanalytical applications. 

PMID- 25866272
TI  - Aptamers: molecular tools for medical diagnosis.
AB  - Aptamers have been increasingly applied in biomedical field as a class of
      biorecognition elements that possess many advantages such as high specificity and
      binding affinity, easy synthesis, easy modification, small size, non-toxicity and
      good stability. Many diseases like cancer exhibit cellular aberrations at
      morphological and molecular levels. Medical diagnosis based on molecular features
      can be highly specific and extremely sensitive when proper recognition molecule
      and an efficient signal transduction system are employed. However, bioanalysis of
      human diseases at the molecular level is an extremely challenging field because
      effective probes to identify and recognize biomarkers of diseases are not readily
      available. Traditional bio-recognition molecule, antibody has been exploited to
      develop excellent diagnosis assays in many formats, but antibodies are
      insufficient to match the requirements of fast and portable biosensors for point
      of-care applications, which are at high demand in pathogenic bacteria detection
      as well as other diseases like cancer. Aptamers are short single-stranded
      oligonucleotides, which can be selected from random combinatorial library by
      SELEX in vitro. This relatively new biorecognition agent has superior intrinsic
      characteristics for biosensor development. In this review, we first present major
      aptamer selection technologies and the main formats of biosensors, which were
      frequently employed in aptasensor development. Then, the current state of
      aptamers as applied to medical diagnosis was discussed for specifically cancer
      and pathogen diagnosis. Finally, an overview of aptamer-nanomaterials conjugates
      was presented in many applications such as diagnosis, bioimaging, and
      theranostics. 

PMID- 25866273
TI  - Potential Therapeutic Advantages of Doxorubicin when Activated by Formaldehyde to
      Function as a DNA Adduct-Forming Agent.
AB  - Doxorubicin has been in use as a key anticancer drug for forty years, either as a
      single agent or in combination chemotherapy. It functions primarily by
      interfering with topoisomerase II activity but in the presence of formaldehyde,
      it forms adducts with DNA, mainly with the exocyclic amine of guanine at GpC
      sites and these adducts are more cytotoxic than topoisomerase II induced damage.
      High levels of adducts form spontaneously from the endogenous level of
      formaldehyde in tumour cells (1,300 adducts per cell after a 4 hr treatment with
      doxorubicin), but substantially higher levels form with the addition of exogenous
      sources of formaldehyde, such as formaldehyde releasing prodrugs. The enhanced
      cytotoxicity of adducts has been confirmed in mouse models, with adduct-forming
      conditions resulting in much improved inhibition of tumour growth, as well as
      cardioprotection. Doxorubicin cardiotoxicity has been attributed to topoisomerase
      II poisoning, and the cardioprotection is consistent with a mechanism switch from
      topoisomerase II poisoning to covalent adduct formation. Although the adducts
      have a half-life of less than one day, a population remains as essentially
      permanent lesions. The capacity of doxorubicin to form adducts offers a range of
      potential advantages over the conventional use of doxorubicin (as a topoisomerase
      II poison), including: enhanced cell kill; tumour-selective activation, hence
      tumour-selective cell kill; decreased cardiotoxicity; decreased resistance to
      prolonged doxorubicin treatment. There is therefore enormous potential to improve
      clinical responses to doxorubicin by using conditions which favour the formation
      of doxorubicin-DNA adducts. 

PMID- 25866275
TI  - Targeting Transcription Factor Binding to DNA by Competing with DNA Binders as an
      Approach for Controlling Gene Expression.
AB  - Transcription factors are recognized as the master regulators of gene expression.
      Interestingly, about 10% of the transcription factors described in mammals are up
      to date directly implicated in a very large number of human diseases. With the
      exception of ligand-inducible nuclear receptors, transcription factors have
      longtime been considered as "undruggable" targets for therapeutics. However, the
      significant breakthroughs in their protein biochemistry and interactions with DNA
      at the structural level, together with increasing needs for new targeted
      approaches particularly in cancers, has changed this postulate and opened the way
      for targeting transcription factors. Along with a better knowledge of their
      specific DNA binding sequences by genome wide and high throughput sequencing
      assay, these informations make possible the potent targeting of the transcription
      factors by three approaches dependently of their mechanism of action. In this
      review, we discuss the different physicochemical interactions between the
      transcription factors and the DNA helix, and the protein/protein interactions
      within a transcription factor complex and their impacts on the DNA structure. In
      order to impair transcription factor activities, small molecules compounds can
      either act by direct interaction on the transcription factor, or by blocking the
      protein/protein interactions in a transcription complex, or by competing with the
      transcription factor itself and specifically targeting its cognate binding
      sequence. For this latter mode of transcription targeting, we pay special
      attention to the DNA intercalating, alkylating or groove binders for
      transcription factor/DNA binding modulation. 

PMID- 25866276
TI  - The Interaction of DNA-Binding Ligands with Trinucleotide-Repeat DNA:
      Implications for Therapy and Diagnosis of Neurological Disorders.
AB  - Expansion of trinucleotide repeats (TNRs) within genes plays a major role in
      pathology of various neurological diseases. The correlations of these unusual
      repetitive sequences with the aetiology of these diseases and the mechanism by
      which those repeats are expanded during replication have been extensively
      studied. Small-molecule ligands that bind to TNRs could provide potent biological
      applications. First, the length of the TNR is the most important determinant of
      these neurological diseases. Ligands that reduce the repeat length or impair
      repeat expansion may be used to delay onset and reduce the severity of these
      diseases. Interestingly, many important anticancer ligands and antibiotics have
      desirable qualities when interacting with TNR DNA, and may form the basis for the
      development of novel therapeutics against neurological diseases. Second, designed
      ligands that bind to expanded TNRs with high specificity based on the structural
      and chemical characteristics of these repeats can serve as diagnostic tools for
      determining repeat length and may have applications in preventive medicine. In
      this article we will review our current understanding of the interaction between
      DNA-binding ligands and TNRs. 

PMID- 25866277
TI  - Minor-Groove Binding Agents: Rational Design of Carboxamide Bond Isosteres.
AB  - Distamycin and netropsin analogues have been designed for targeting specific
      sequences in DNA. Numerous reviews have been centered on the replacement of N
      methylpyrrole with heteroaromatic rings in order to induce better fitting to
      improve the binding efficiency and the introduction of additional interactions
      for recognition of GC base pairs at the minor groove of DNA. Most of these
      designed analogs retained the use of carboxamide-bond for interconnecting the
      heteroaromatic rings. Computer simulations of netropsin and distamycin has
      pinpointed the advantages of designing isosteres of the carboxamide-bond for
      amplifying or attenuating particular interactions to DNA, but have been less
      studied. The key challenges that must be overcome to realize this goal are the
      development of feasible synthetic methodologies. This review examined in detail
      for the first time the electronic, structural, and conformational attributes of
      the various carboxamide isosteres: (i) neutral isostere-alkenyl and alkyl, (ii)
      hydrogen donating isostere-urea and carbonylurea, and (iii) hydrogen acceptor
      isosteres-diazene and diketone. In particular, the ability of these isosteres to
      participate in non-covalent interactions by tuning the shape and hydrogen bonding
      to the floor of the minor groove is compared with that of the carboxamide bond.
      We hope this review will encourage the development of a library of modified
      isosteres of the carboxamide bond which target DNA with excellent sequence
      specificity, stronger binding affinity and exhibit improved biological
      properties. Another goal is to develop synthetic methodolgies for the ready
      synthesis of poly-isosteric bond used in mimicking of the poly-carboxamide bond
      for DNA minor groove binding agents, the area in which progress has been slow. 

PMID- 25866274
TI  - Structural and Functional Diversity of Estrogen Receptor Ligands.
AB  - Estrogen receptors, comprised of ERalpha and ERbeta isoforms in mammals, act as
      ligandmodulated transcription factors and orchestrate a plethora of cellular
      functions from sexual development and reproduction to metabolic homeostasis.
      Herein, I revisit the structural basis of the binding of ERalpha to DNA and
      estradiol in light of the recent discoveries and emerging trends in the field of
      nuclear receptors. A particular emphasis of this review is on the chemical and
      structural diversity of an everincreasing repertoire of physiological,
      environmental and synthetic ligands of estrogen receptors that ultimately
      modulate their interactions with cognate DNA located within the promoters of
      estrogenresponsive genes. In particular, modulation of estrogen receptors by
      small molecule ligands represents an important therapeutic goal toward the
      treatment of a wide variety of human pathologies including breast cancer,
      cardiovascular disease, osteoporosis and obesity. Collectively, this article
      provides an overview of a wide array of small organic and inorganic molecules
      that can fine-tune the physiological function of estrogen receptors, thereby
      bearing a direct impact on human health and disease. 

PMID- 25866278
TI  - Therapeutic Agents Based on DNA Sequence Specific Binding.
AB  - DNA interactive agents have been used in the clinical setting for the treatment
      of cancer since the beginning of modern-era chemotherapy. Despite a shift of
      focus towards molecular targeted therapy, DNA remains a critical macromolecular
      target for anti-cancer intervention and the next generation of agents must
      conform to the optimum combination of increased therapeutic activity and reduced
      off-target toxicity. We evaluate the potential of non-covalent DNA binding small
      molecules as "gene-control" agents, exploiting inherent or engineered sequence
      selectivity, to target critical genomic sequences. In addition we review examples
      of natural products and synthetic derivatives that exert their activity through
      sequence specific DNA-covalent modification. 

PMID- 25866280
TI  - Medicinal chemistry of aptamers.
AB  - Aptamers- short nucleic acid or peptide ligands- attracted considerable attention
      across various disciplines as target specific therapeutic, delivery vehicle and
      diagnostic tools. The applicability of aptamers - often termed as 'chemical
      antibodies' - continues to grow and possess certain edge over the antibody
      counterpart. In this special issue, we have invited seven contributors to
      highlight the chemical biology, therapeutic, biosensor and imaging applications
      of aptamers. Furthermore, the issue end with an outlook of aptamer technology
      after 25 years of history. 

PMID- 25866279
TI  - DNA Recognition by a Novel Bis-Intercalator, Potent Anticancer Drug XR5944.
AB  - XR5944 is a potent anticancer drug with a novel DNA binding mode: DNA
      bisintercalationg with major groove binding. XR5944 can bind the estrogen
      response element (ERE) sequence to block ER-ERE binding and inhibit ERalpha
      activities, which may be useful for overcoming drug resistance to currently
      available antiestrogen treatments. This review discusses the progress relating to
      the structure and function studies of specific DNA recognition of XR5944. The
      sites of intercalation within a native promoter sequence appear to be different
      from the ideal binding site and are context- and sequence- dependent. The
      structural information may provide insights for rational design of improved
      EREspecific XR5944 derivatives, as well as of DNA bis-intercalators in general. 

PMID- 25866281
TI  - Immigrants in immunology: the benefits of lax borders.
AB  - The field of immunology has a long history of illuminating fundamental biological
      processes of critical importance to human health. From an outsider's perspective,
      the questions are profoundly philosophical and the experimental approaches are
      elegantly precise. Yet immunology can also appear impenetrable. Here we recount
      the experience of two graduate students from the fields of ecology and computer
      science, who have immigrated into immunological terrain attracted by systems
      level questions. We argue that such migrations enrich the field of immunology,
      and that cultural and institutional changes are needed to promote more
      interdisciplinary explorations. 

PMID- 25866282
TI  - Linker length and flexibility induces new cellobiohydrolase activity of PoCel6A
      from Penicillium oxalicum.
AB  - In a previous study, a novel cellobiohydrolase, PoCel6A, with new enzymatic
      activity against p-nitrophenyl-beta-D-cellobioside (pNPC), was purified from
      Penicillium oxalicum. The cellulose-binding module and catalytic domain of
      PoCel6A showed a high degree of sequence similarity with other fungal Cel6As.
      However, PoCel6A had 11 more amino acids in the linker region than other Cel6As.
      To evaluate the relationship between the longer linker of PoCel6A and its
      enzymatic activity, 11 amino acids were deleted from the linker region of
      PoCel6A. The shortened PoCel6A linker nullified the enzymatic activity against
      pNPC but dramatically increased the enzyme's capacity for crystalline cellulose
      degradation. The shortened linker segment appeared to have no effect on the
      secondary structural conformation of PoCel6A. Another variant (PoCel6A-6pro) with
      six consecutive proline residues in the interdomain linker had a higher rigid
      linker, and no enzymatic activity was observed against soluble and insoluble
      substrate. The flexibility of the linker had an important function in the
      formation of active cellulase. The length and flexibility of the linker is
      clearly able to modify the function of PoCel6A and induce new characteristics of
      Cel6A. 

PMID- 25866283
TI  - Simple and Sensitive Point-of-Care Bioassay System Based on Hierarchically
      Structured Enzyme-Mimetic Nanoparticles.
AB  - An enzyme-mimetic nanoparticle-based point of care bioassay device is developed
      for rapid and sensitive detection of analytes. Digital images acquired by smart
      cellular phones allow quantifying the amounts of analytes. Using this new device,
      quantitative analysis of liquid sample is performed within 15 min with an order
      of magnitude enhancement of sensitivity compared with conventional Au
      nanoparticle-based devices. 

PMID- 25866284
TI  - Exercise after spinal cord injury as an agent for neuroprotection, regeneration
      and rehabilitation.
AB  - Spinal cord injury (SCI) is a traumatic event from which there is limited
      recovery of function, despite the best efforts of many investigators to devise
      realistic therapeutic treatments. Partly this is due to the multifaceted nature
      of SCI, where there is considerable disarray and dysfunction secondary to the
      initial injury. Contributing to this secondary degeneration is neurotoxicity,
      vascular dysfunction, glial scarring, neuroinflammation, apoptosis and
      demyelination. It seems logical that addressing the need for neuroprotection,
      regeneration and rehabilitation will require different treatment strategies that
      may be applied at varied stages of the post-injury response. Here we focus on a
      single strategy, exercise/physical training, which appears to have multiple
      applications and benefits for an acute or chronic SCI. Exercise has been
      demonstrated to be advantageous at cellular and biochemical levels, as well as
      being of benefit for the whole animal or human subject. Data from our lab and
      others will be discussed to further elucidate the many positive aspects of
      implementing exercise following injury and to suggest that rehabilitation is not
      the sole target of a training regimen following SCI. This article is part of a
      Special Issue entitled SI: Spinal cord injury. 

PMID- 25866285
TI  - Effects of the beta-adrenergic receptor antagonist Propranolol on dyskinesia and
      L-DOPA-induced striatal DA efflux in the hemi-parkinsonian rat.
AB  - Dopamine (DA) replacement therapy with L-DOPA continues to be the primary
      treatment of Parkinson's disease; however, long-term therapy is accompanied by L
      DOPA-induced dyskinesias (LID). Several experimental and clinical studies have
      established that Propranolol, a beta-adrenergic receptor antagonist, reduces LID
      without affecting L-DOPA's efficacy. However, the exact mechanisms underlying
      these effects remain to be elucidated. The aim of this study was to evaluate the
      anti-dyskinetic profile of Propranolol against a panel of DA replacement
      strategies, as well as elucidate the underlying neurochemical mechanisms. Results
      indicated that Propranolol, in a dose-dependent manner, reduced LID, without
      affecting motor performance. Propranolol failed to alter dyskinesia produced by
      the D1 receptor agonist, SKF81297 (0.08 mg/kg, sc), or the D2 receptor agonist,
      Quinpirole (0.05 mg/kg, sc). These findings suggested a pre-synaptic mechanism
      for Propranolol's anti-dyskinetic effects, possibly through modulating L-DOPA
      mediated DA efflux. To evaluate this possibility, microdialysis studies were
      carried out in the DA-lesioned striatum of dyskinetic rats and results indicated
      that co-administration of Propranolol (20 mg/kg, ip) was able to attenuate L-DOPA
      (6 mg/kg, sc) induced DA efflux. Therefore, Propranolol's anti-dyskinetic
      properties appear to be mediated via attenuation of L-DOPA-induced
      extraphysiological efflux of DA.

PMID- 25866286
TI  - Validity of diagnostic codes and laboratory tests of liver dysfunction to
      identify acute liver failure events.
AB  - PURPOSE: Identification of acute liver failure (ALF) is important for post
      marketing surveillance of medications, but the validity of using ICD-9 diagnoses
      and laboratory data to identify these events within electronic health records is
      unknown. We examined positive predictive values (PPVs) of hospital ICD-9
      diagnoses and laboratory tests of liver dysfunction for identifying ALF within a
      large, community-based integrated care organization. METHODS: We identified
      Kaiser Permanente Northern California health plan members (2004-2010) with a
      hospital diagnosis suggesting ALF (ICD-9 570, 572.2, 572.4, 572.8, 573.3, 573.8,
      or V42.7) plus an inpatient international normalized ratio >=1.5 (off warfarin)
      and total bilirubin >=5.0 mg/dL. Hospital records were reviewed by hepatologists
      to adjudicate ALF events. PPVs for confirmed outcomes were determined for
      individual ICD-9 diagnoses, diagnoses plus prescriptions for hepatic
      encephalopathy treatment, and combinations of diagnoses in the setting of
      coagulopathy and hyperbilirubinemia. RESULTS: Among 669 members with no pre
      existing liver disease, chart review confirmed ALF in 62 (9%). Despite the
      presence of co-existing coagulopathy and hyperbilirubinemia, individual ICD-9
      diagnoses had low PPVs (range, 5-15%); requiring prescriptions for encephalopathy
      treatment did not increase PPVs of these diagnoses (range, 2-23%). Hospital
      diagnoses of other liver disorders (ICD-9 573.8) plus hepatic coma (ICD-9 572.2)
      had high PPV (67%; 95%CI, 9-99%) but only identified two (3%) ALF events.
      CONCLUSIONS: Algorithms comprising relevant hospital diagnoses, laboratory
      evidence of liver dysfunction, and prescriptions for hepatic encephalopathy
      treatment had low PPVs for confirmed ALF events. Studies of ALF will need to rely
      on medical records to confirm this outcome.

PMID- 25866287
TI  - Ethics in the use of extracorporeal cardiopulmonary resuscitation in adults.
AB  - Extracorporeal cardiopulmonary resuscitation (ECPR) promises to be an important
      advance in the treatment of cardiac arrest. However, ECPR involves ethical
      challenges that should be addressed as it diffuses into practice. Benefits and
      risks are uncertain, so the evidence base needs to be further developed, at least
      through outcomes registries and potentially with randomized trials. To inform
      decision making, patients' preferences regarding ECPR should be obtained, both
      from the general population and from inpatients at risk for cardiac arrest. Fair
      and transparent appropriate use criteria should be developed and could be
      informed by economic analyses. 

PMID- 25866288
TI  - Force and depth of mechanical chest compressions and their relation to chest
      height and gender in an out-of-hospital setting.
AB  - INTRODUCTION: The LUCAS 2 device stores technical data that documents the chest
      compression process. We analyzed chest wall dimensions and mechanics stored
      during chest compressions on humans using data gathered with the LUCAS 2 device.
      METHODS: Data from LUCAS 2 devices used in out-of-hospital cardiac arrest were
      downloaded with dedicated proprietary software and matched to the corresponding
      patient data. Cases were included only if the suction cup was placed correctly,
      if it was not realigned during the first 5 min of chest compressions, and if no
      other anomaly in device use was noted. Trauma cases were excluded. RESULTS:
      Ninety-five patients were included. All patients received manual cardiopulmonary
      resuscitation prior to the application of the device. The mean (SD) chest height
      was 232 (25)mm for males and 209 (26)mm for females (P < 0.001). The mean (min
      max) compression depth in patients with chest height >185 mm was 53 (50-55)mm,
      corresponding with 19-28% of the chest diameter. The mean force required to
      achieve the compression depth of 53 mm ranged between 219 and 568 N. No
      correlation was found between chest height and force to reach 53 mm depth
      (females: R(2) = 0.001, males: R(2) = 0.007). CONCLUSION: There was a large
      variation of the required force to achieve a compression depth of 53 mm. No
      correlation was seen between chest height and maximum force required to compress
      the chest 53 mm.

PMID- 25866289
TI  - Mechanical and manual CPR. A further analysis of LINC data: Are you ready to
      think about being outside the box?

PMID- 25866290
TI  - A novel 96well-formatted micro-gap plate enabling drug response profiling on
      primary tumour samples.
AB  - Drug-based treatments are the most widely used interventions for cancer
      management. Personalized drug response profiling remains inherently challenging
      with low cell count harvested from tumour sample. We present a 96well-formatted
      microfluidic plate with built-in micro-gap that preserves up to 99.2% of cells
      during multiple assay/wash operation and only 9,000 cells needed for a single
      reagent test (i.e. 1,000 cells per test spot x 3 selected concentration x
      triplication), enabling drug screening and compatibility with conventional
      automated workstations. Results with MCF7 and MDA-MB-231 cell lines showed that
      no statistical significance was found in dose-response between the device and
      conventional 96-well plate control. Primary tumour samples from breast cancer
      patients tested in the device also showed good IC50 prediction. With drug
      screening of primary cancer cells must consider a wide range of scenarios, e.g.
      suspended/attached cell types and rare/abundant cell availability, the device
      enables high throughput screening even for suspended cells with low cell count
      since the signature microfluidic cell-trapping feature ensures cell preservation
      in a multiple solution exchange protocol. 

PMID- 25866291
TI  - Manganese superoxide dismutase (SOD2/MnSOD)/catalase and SOD2/GPx1 ratios as
      biomarkers for tumor progression and metastasis in prostate, colon, and lung
      cancer.
AB  - The role of manganese-dependent superoxide dismutase (SOD2/MnSOD) during tumor
      progression has been studied for several decades with controversial results.
      While SOD2 downregulation was initially associated with tumor initiation and was
      proposed as a tumor suppressor gene, recent studies have reported that SOD2 might
      favor tumor progression and dissemination. To our knowledge this is the first
      time that changes in SOD2 expression in three different types of tumors, i.e.,
      prostate, lung, and colon cancer, are studied by analyzing both SOD2 mRNA and
      protein levels in a total of 246 patients' samples. In prostate samples, SOD2
      protein levels were also increased, especially in middle stage tumors. In the
      case of colon and lung tumors both mRNA and protein SOD2 levels were increased in
      malignant tissues compared to those in nontumor samples. More importantly, all
      metastases analyzed showed increased levels of SOD2 when compared to those of
      normal primary tissue and healthy adjacent tissue. Together, these results
      suggest that a common redox imbalance in these three types of tumor occurs at
      intermediate stages which then might favor migration and invasion, leading to a
      more aggressive cancer type. Consequently, the ratios SOD2/catalase and SOD2/Gpx1
      could be considered as potential markers during progression from tumor growth to
      metastasis.

PMID- 25866292
TI  - Isocratic and gradient elution in micellar liquid chromatography with Brij-35.
AB  - Polyoxyethylene(23)lauryl ether (known as Brij-35) is a nonionic surfactant,
      which has been considered as an alternative to the extensively used in micellar
      liquid chromatography anionic surfactant sodium lauryl (dodecyl) sulfate, for the
      analysis of drugs and other types of compounds. Brij-35 is the most suitable
      nonionic surfactant for micellar liquid chromatography, owing to its commercial
      availability, low cost, low toxicity, high cloud temperature, and low background
      absorbance. However, it has had minor use. In this work, we gather and discuss
      some results obtained in our laboratory with several beta-blockers, sulfonamides,
      and flavonoids, concerning the use of Brij-35 as mobile phase modifier in the
      isocratic and gradient modes. The chromatographic performance for purely micellar
      eluents (with only surfactant) and hybrid eluents (with surfactant and
      acetonitrile) is compared. Brij-35 increases the polarity of the alkyl-bonded
      stationary phase and its polyoxyethylene chain with the hydroxyl end group allows
      hydrogen-bond interactions, especially for phenolic compounds. This offers the
      possibility of using aqueous solutions of Brij-35 as mobile phases with
      sufficiently short retention times. The use of gradients of acetonitrile to keep
      the concentration of Brij-35 constant is another interesting strategy that yields
      a significant reduction in the peak widths, which guarantee high resolution. 

PMID- 25866293
TI  - Modeling tensorial conductivity of particle suspension networks.
AB  - Significant microstructural anisotropy is known to develop during shearing flow
      of attractive particle suspensions. These suspensions, and their capacity to form
      conductive networks, play a key role in flow-battery technology, among other
      applications. Herein, we present and test an analytical model for the tensorial
      conductivity of attractive particle suspensions. The model utilizes the mean
      fabric of the network to characterize the structure, and the relationship to the
      conductivity is inspired by a lattice argument. We test the accuracy of our model
      against a large number of computer-generated suspension networks, based on
      multiple in-house generation protocols, giving rise to particle networks that
      emulate the physical system. The model is shown to adequately capture the
      tensorial conductivity, both in terms of its invariants and its mean
      directionality. 

PMID- 25866294
TI  - Structural Hippocampal Damage Following Anti-N-Methyl-D-Aspartate Receptor
      Encephalitis.
AB  - BACKGROUND: The majority of patients with anti-N-methyl-D-aspartate receptor
      (NMDAR) encephalitis suffer from persistent memory impairment despite
      unremarkable routine clinical magnetic resonance imaging. With improved acute
      care in these patients, neurocognitive impairment represents the major
      contributor to long-term morbidity and has thus become a focus of attention.
      METHODS: Forty patients with anti-NMDAR encephalitis after the acute disease
      stage and 25 healthy control subjects underwent multimodal structural imaging
      that combined volumetry of hippocampal subfields with analysis of hippocampal
      microstructural integrity. Verbal and visuospatial memory performance was
      assessed in all patients and correlation and mediation analyses were performed to
      examine associations between hippocampal structural integrity, memory
      performance, and disease severity. RESULTS: Hippocampal volumes were
      significantly reduced in patients and hippocampal subfield analysis revealed
      bilateral atrophy of the input and output regions of the hippocampal circuit.
      Microstructural integrity was impaired in both hippocampi in patients.
      Importantly, hippocampal volumetric and microstructural integrity measures
      correlated with memory performance and disease severity and duration. Mediation
      analysis revealed that hippocampal microstructure mediated the effect of disease
      severity on memory performance. CONCLUSIONS: Data from this largest cohort of
      anti-NMDAR encephalitis patients that underwent extensive multimodal magnetic
      resonance imaging demonstrate that structural hippocampal damage and associated
      memory deficits are important long-term sequelae of the encephalitis. Correlation
      with disease duration and severity highlights the need for rapid diagnosis and
      adequate immunotherapy to prevent persistent damage to the hippocampus. Advanced
      imaging protocols may allow a more detailed analysis of structural damage to
      assess disease progression in clinical routine examinations and for therapy
      evaluation in prospective trials.

PMID- 25866295
TI  - Citation Distortions in the Literature on the Serotonin-Transporter-Linked
      Polymorphic Region and Amygdala Activation.

PMID- 25866296
TI  - Ion-dipole interactions and their functions in proteins.
AB  - Ion-dipole interactions in biological macromolecules are formed between atomic or
      molecular ions and neutral protein dipolar groups through either hydrogen bond or
      coordination. Since their discovery 30 years ago, these interactions have proven
      to be a frequent occurrence in protein structures, appearing in everything from
      transporters and ion channels to enzyme active sites to protein-protein
      interfaces. However, their significance and roles in protein functions are
      largely underappreciated. We performed PDB data mining to identify a sampling of
      proteins that possess these interactions. In this review, we will define the ion
      dipole interaction and discuss several prominent examples of their functional
      roles in nature. 

PMID- 25866297
TI  - Evolving Role of Local Anesthetics in Managing Postsurgical Analgesia.
AB  - PURPOSE: Opioid analgesics, the cornerstone of effective postsurgical pain
      management, may be associated with risk of opioid-related adverse drug events
      (ADEs) that may complicate the postsurgical experience. Perioperative multimodal
      analgesic regimens have the potential to improve postsurgical pain control and
      may permit use of lower analgesic doses and reduce the incidence of opioid
      related ADEs. Utility of traditional local anesthetic formulations to provide
      analgesia over the entire postsurgical period is limited by their short duration
      of action. Liposome bupivacaine, a liposomal formulation of bupivacaine indicated
      for single-dose administration into the surgical site to produce postsurgical
      analgesia, was evaluated in multiple surgical models as part of multimodal
      analgesic regimens and was found in clinical trials to provide postsurgical
      analgesia for up to 72 hours. Here, we provide an overview of the available
      multimodal analgesic options and recent recommendations for optimal postsurgical
      pain management. METHODS: A review of the literature was conducted, and results
      from recent clinical trials are included. FINDINGS: The use of a multimodal
      analgesic regimen, including liposome bupivacaine, can extend the time to first
      postsurgical opioid use, may reduce postsurgical opioid consumption, and reduce
      hospital length of stay and costs compared with an opioid-only analgesic regimen.
      IMPLICATIONS: Use of multimodal analgesic regimens is a practical way to achieve
      good postsurgical analgesia while minimizing reliance on opioids and associated
      adverse events. Taken as a whole, evidence from the clinical studies of liposome
      bupivacaine suggests this local anesthetic formulation may be a useful component
      of multimodal analgesic regimens for managing postsurgical pain in select
      patients, with the potential to reduce opioid use and opioid-related ADEs in the
      postsurgical setting. As with bupivacaine, appropriate use of liposome
      bupivacaine to optimize clinical effects, economic implications, and patient
      tolerability will depend on appropriate patient selection, practitioner training,
      and institutional protocols. As a component of a multimodal analgesic regimen,
      liposome bupivacaine represents a new approach to extending the duration of
      postsurgical analgesia. Further studies across a range of surgical settings
      should help clarify the most appropriate roles for this prolonged-release
      formulation of bupivacaine.

PMID- 25866299
TI  - Vitamin C in the treatment and/or prevention of obesity.
AB  - Obesity has emerged as one of the major health threats worldwide. Moreover, an
      excessive body fat accumulation, which defines this disease, could lead to
      several associated clinical manifestations such as cardiovascular events, type 2
      diabetes, inflammation, and some types of cancer. The appearance of these co
      morbidities has been often related to an unbalanced oxidative stress. Therefore,
      antioxidant-based treatments could be considered as interesting approaches to
      possibly counteract obesity fat accumulation complications. In this context, it
      has been observed that vitamin C intake (ascorbic acid) is negatively associated
      with the occurrence of several conditions such as hypertension, gallbladder
      disease, stroke, cancers, and atherosclerosis, and also with the onset of obesity
      in humans and animals. Among the possible beneficial effects of ascorbic acid on
      obesity-related mechanisms, it has been suggested that this vitamin may: (a)
      modulate adipocyte lipolysis; (b) regulate the glucocorticoid release from
      adrenal glands; (c) inhibit glucose metabolism and leptin secretion on isolated
      adipocytes; (d) lead to an improvement in hyperglycemia and decrease
      glycosylation in obese-diabetic models; and (e) reduce the inflammatory response.
      Possibly, all these features could be related with the outstanding antioxidant
      characteristics of this vitamin. Thus, the present article reviews the up-to-date
      evidence regarding in vitro and in vivo effects of vitamin C in obesity and its
      co-morbidities. 

PMID- 25866298
TI  - Gastrointestinal Events Among Patients Initiating Osteoporosis Therapy: A
      Retrospective Administrative Claims Database Analysis.
AB  - PURPOSE: Our purpose was to characterize the occurrence of gastrointestinal (GI)
      events among women on oral bisphosphonate therapy. METHODS: This was a
      retrospective cohort study that used a United States (US) claims database. The
      study period was from January 1, 2000, to December 31, 2011. The index date was
      the date of the first oral bisphosphonate (alendronate, ibandronate, or
      risedronate) prescription and occurred between January 1, 2001, and December 31,
      2010. The pre- and post-index periods were the 1-year periods before and after
      the index date, respectively. The analysis included women with osteoporosis aged
      >=55 years at the index date who were naive to all osteoporosis treatments before
      the index date and were continuously enrolled in the health plan for at least 1
      year before and 1 year after the index date. Patients with a diagnosis of
      malignant neoplasm during the pre- or post-index periods or a diagnosis of Paget
      disease anytime in the claims history were excluded. The occurrence of GI events
      (defined as esophagitis; gastroesophageal reflux disease; ulcer, stricture,
      perforation, or hemorrhage of the esophagus; gastric, duodenal, or peptic ulcer;
      acute gastritis; duodenitis; GI hemorrhage; nausea/vomiting; or dysphagia) was
      assessed during the pre-index period and at 3, 6, and 12 months in the post-index
      period. The rate of GI events was defined as the percentage of patients having at
      least 1 GI event in each analysis period (ie, pre-index and post-index periods).
      GI events in the post-index period were also stratified by the presence of GI
      events in the pre-index period. FINDINGS: A total of 75,593 women were included
      in the analysis. The average age at the index date was 64.4 years.
      Gastroprotective agents were used by 17.9% of patients. Approximately one fourth
      of patients (26.6%; n = 20,073) had >=1 GI events in the pre-index period.
      Approximately the same proportion of patients (28.0%; n = 21,142) experienced GI
      events in the post-index period. The cumulative rate of GI events during the post
      index period was higher among patients who had GI events in the pre-index period
      (51.2%) than among patients without a GI event in the pre-index period (19.6%).
      IMPLICATIONS: Among women with osteoporosis enrolled in a US commercial plan, GI
      events were common regardless of bisphosphonate use. Approximately one fourth of
      US women on bisphosphonate therapy experienced GI events within the year after
      initiation of therapy, and one half of US women with a previous GI event had
      another event while taking bisphosphonates.

PMID- 25866300
TI  - alpha-Tocopherol status and altered expression of alpha-tocopherol-related
      proteins in streptozotocin-induced type 1 diabetes in rat models.
AB  - Vitamin E plays a critical role as an antioxidant in several pathological
      conditions, including diabetes, cancer, cardiovascular diseases, and
      neurodegenerative disorders. Diabetes is a metabolic disorder of glucose due to
      the lack of adequate insulin production (type 1) or peripheral insulin resistance
      (type 2). Oxidative stress plays a major role in the pathogenesis of diabetes and
      its complications. The purpose of the present study was to determine alpha
      tocopherol status and the expression of alpha-tocopherol-related proteins,
      including binding proteins and metabolizing enzymes, under streptozotocin (STZ)
      induced type 1 diabetes in rat models. In STZ rats, plasma alpha-tocopherol
      levels decreased compared to the control rats, whereas hepatic alpha-tocopherol
      levels in the STZ rats were significantly increased. CuZn-superoxide dismutase
      (SOD) gene expression in the liver of STZ rats was markedly decreased, whereas Mn
      SOD gene expression remained unaltered. Accelerated lipid peroxidation in the
      liver of STZ rats was observed and the hepatic expression of alpha-tocopherol
      transfer protein (alpha-TTP) in STZ rats decreased compared to that in the
      controls. The hepatic expression of cytochrome P450 4F2 (CYP4F2) and CYP3A2 genes
      in STZ rats also decreased. The reduced expression of hepatic alpha-TTP and
      CYP4F2 genes probably leads to decreased plasma alpha-tocopherol levels and
      elevated alpha-tocopherol levels in the liver of STZ rats. The altered expression
      of hepatic alpha-tocopherol-related proteins might regulate alpha-tocopherol
      status in type 1 diabetes. Determining the mechanism of modulating alpha
      tocopherol status may be helpful in promoting antioxidant therapy in diabetes. 

PMID- 25866301
TI  - Estimation of food portion sizes frequently consumed by children 3-6 years old in
      Japan.
AB  - No study has documented Japanese children's food portion sizes. Since this
      information is essential to establish valid measurement tools and effective
      education methods for dietary intake, we measured them using one-day, semi
      weighed diet records (DRs) for 489 Japanese children aged 3-6 y. Each food's
      frequency of appearance on the DRs was counted. If a child consumed a certain
      food more than once per day, an average weight for that food was calculated and
      used in the portion size calculation as that child's representative value. In
      total, 67 food items were consumed by twenty or more children. We calculated the
      mean, standard deviation, median, minimum, and maximum portion size values for
      these food items. In addition to these 67 items, Chinese noodles and water were
      included in the analysis. The most frequently consumed food was well-milled rice
      (mean portion size for rice=79 g), which was consumed by 350 children, followed
      by soy sauce (4 g), eggs (26 g), and carrots (9 g). Among the five most
      frequently consumed foods, portion sizes of rice and pork but not milk, eggs, or
      carrots significantly increased with age, height, and weight. In multivariate
      linear regression analysis, however, the significant relationships between rice
      portion size and age were not observed. Regarding pork, only the relationship
      with height was significant. A sex difference was detected in the rice and milk
      portion sizes. Most of portion sizes observed here were apparently smaller than
      those reported among United Kingdom children. This study provides important basic
      information for the implementation of quantitative nutritional research and
      educational efforts for Japanese preschool children. 

PMID- 25866302
TI  - Dietary iron overload: short- and long-term effects on cecal morphometry in
      growing rats.
AB  - In animal models, Fe overload is associated with organ oxidative stress and
      tissue injury. In this context, luminal Fe may affect the mucosal barrier and
      function or generate a pathological milieu in the intestine that triggers
      epithelial cell stress. Here, we hypothesized that increased liver Fe levels
      resulting from dietary Fe overload may be associated with architectural changes
      in the cecal mucosa. Weanling male Wistar rats (n=7-10/group) were fed diets
      (modified from AIN-93G) containing adequate or supplemental Fe (approximately 10
      times the recommended levels) for 4 and 12 wk. At euthanasia, the blood Hb was
      determined, and Fe analyses were performed in stool and liver samples using
      atomic absorption spectrophotometry. Cecal tissue was collected for histological
      and morphometric analysis. No significant differences were observed in the blood
      Hb or Hb Fe pool between groups in either period. Iron overload led to a higher
      fecal Fe excretion, whereas the liver Fe was increased only after 12 wk when
      compared with controls. After 4 wk, the consumption of Fe-overloaded diets
      resulted in changes in the mucosal architecture of the cecum, which were
      intensified after 12 wk. At this time, these changes were significantly
      correlated with the hepatic Fe content. These findings suggest that changes in
      the cecal mucosa may have occurred as a result of oxidative stress caused by
      excessive amounts of Fe in the intestinal lumen. The consequences of these
      effects on the intestinal absorption and its implications for liver Fe
      homeostasis should be considered in future studies. 

PMID- 25866303
TI  - [6]-gingerol induces electrogenic sodium absorption in the rat colon via the
      capsaicin receptor TRPV1.
AB  - [6]-Gingerol possesses a variety of beneficial pharmacological and therapeutic
      properties, including anti-carcinogenic, anti-inflammatory, and anti-emetic
      activities. Although [6]-gingerol is known to regulate the contraction of the
      intestine, its effect on intestinal ion transport is unclear. The aim of this
      study was to examine the role of [6]-gingerol in the regulation of electrogenic
      ion transport in the rat intestine by measuring the transmural potential
      difference (DeltaPD). [6]-Gingerol induced significant positive DeltaPD when
      administered to the serosal but not mucosal side of the colon, ileum, and
      jejunum; the highest effect was detected in the colon at a concentration of 10
      MUM. [6]-Gingerol-induced increase in DeltaPD was suppressed by ouabain, an
      inhibitor of Na(+)/K(+)-ATPase, whereas no effect was observed in response to
      bumetanide, an inhibitor of the Na(+)-K(+)-2Cl(-) co-transporter. In addition,
      DeltaPD induction by [6]-gingerol was greatly diminished by capsazepine, an
      inhibitor of the capsaicin receptor TRPV1. These results suggest that [6]
      gingerol induced the electrogenic absorption of sodium in the rat colon via
      TRPV1.

PMID- 25866304
TI  - Beneficial effect of a low dose of ethanol on liver function and serum urate in
      rats fed a high-fat diet.
AB  - This study investigated the effects of the consumption of 1% or 2% (v/v) ethanol
      in drinking water for 12 wk on rats fed a high-fat diet. Body weight gain, food
      intake, and fluid intake were unaffected by ethanol intake. Adipose tissue
      weight, and serum glucose and lipids were unaffected. Compared to the control (no
      ethanol), 1% ethanol intake significantly reduced serum levels of alanine
      aminotransferase (ALT), lactate dehydrogenase (LDH), and ammonia (p<0.05),
      whereas 2% ethanol intake did so to a lesser extent. Serum urate was
      significantly lower in both the 1% and 2% ethanol groups than that in the control
      group (p<0.05). The results suggest a low dose of ethanol has beneficial effects
      on liver function and serum urate in rats fed a high-fat diet. 

PMID- 25866305
TI  - Chronic post-exercise lactate administration with endurance training increases
      glycogen concentration and monocarboxylate transporter 1 protein in mouse white
      muscle.
AB  - Lactate is oxidized as an energy fuel during exercise, and it also plays a key
      role in the regulation of glycogen synthesis in the muscles and liver after
      exercise. Previous studies have suggested that lactate is converted to glycogen
      and stimulates glycogen synthesis. However, it remains unclear whether chronic
      post-exercise lactate administration can increase glycogen storage in skeletal
      muscle. We examined whether 3 wk of chronic post-exercise lactate administration
      with training can increase muscle glycogen storage and whether such changes are
      associated with monocarboxylate transporter 1 (MCT1) protein expression in mice.
      Mice were assigned to receive saline with training (SA+T group; n=6) or lactate
      with training (LA+T group; n=6). All mice performed 40 min of treadmill running
      at 25 m/min, following which they received saline or lactate (2.5 mg/g body
      weight), 6 d/wk for 3 wk. After 3 wk, glycogen concentration at rest was higher
      in the white tibialis anterior (TA; p<0.05, +34%), but not in the red TA, in the
      LA+T group. Protein expression of MCT1, the primary lactate transporter, was
      increased with chronic post-exercise lactate administration in the white TA
      (p<0.05, +32%), but not in the red TA. MCT1 protein expression was significantly
      correlated with muscle glycogen concentration in the red and white TA in both
      groups (p<0.05, r=0.969). These results suggest that chronic lactate
      administration after exercise increases MCT1 protein expression, which can be
      involved in the regulation of the observed increase in muscle glycogen storage
      after exercise training.

PMID- 25866306
TI  - Demographic and lifestyle factors associated with vitamin D status in pregnant
      Japanese women.
AB  - Maternal vitamin D deficiency causes pregnancy complications and delayed skeletal
      development in offspring. This study aimed at identifying demographic and
      lifestyle factors associated with vitamin D status in pregnant Japanese women. A
      total of 284 healthy pregnant women in the second trimester were recruited at a
      university hospital in Tokyo, between June 2010 and July 2011. Serum 25
      hydroxyvitamin D (25(OH)D) concentrations were measured using chemiluminescent
      immunoassay. We assessed vitamin D intake using a self-administered diet history
      questionnaire and asked participants about lifestyle variables, including daily
      duration of sunlight exposure and supplement use. The mean (SD) serum 25(OH)D
      concentration was 9.8 (4.7) ng/mL. Almost 60% of the participants had severe
      vitamin D deficiency (measured as 25(OH)D<10 ng/mL). Multiple regression analysis
      showed that multigravidity, pre-pregnancy non-underweight status, higher energy
      adjusted vitamin D intake, and use of vitamin D supplements were correlated with
      higher serum 25(OH)D concentrations (beta=0.245, beta=-0.119, beta=0.226, and
      beta=0.197, respectively). In the summer investigation, women with longer
      durations of sunlight exposure had significantly higher serum 25(OH)D
      concentrations (beta=0.201) that were unrelated to the factors outlined
      previously. In the winter investigation, women with a high education level had
      higher serum 25(OH)D concentrations than others (beta=0.330). Our results would
      be useful for identifying pregnant women at a high risk of low vitamin D status,
      such as primigravidae and those with pre-pregnancy underweight status, low
      education level, low vitamin D intake, and short durations of sunlight exposure. 

PMID- 25866307
TI  - Pycnogenol supplementation promotes lipolysis via activation of cAMP-dependent
      PKA in ob/ob mice and primary-cultured adipocytes.
AB  - This study investigated the PKA-dependent inhibitory effect of pycnogenol (Pyc)
      on lipolysis using ob/ob mice and primary mouse adipocytes. Supplementation of
      Pyc at 30 mg/kg significantly reduced body weight gain and visceral fat mass. The
      serum and hepatic triglyceride (TG) and total cholesterol (TC) levels were
      reduced by Pyc supplementation, and high density lipoprotein (HDL)-cholesterol
      level significantly increased. In addition, hormone sensitive lipase (HSL) and
      adipose triglyceride lipase (ATGL) mRNA levels increased with Pyc supplementation
      in adipose tissue of ob/ob mice. The treatment of primary cultured adipocytes
      with Pyc at 100 MUg/mL significantly increased glycerol release, cAMP level by
      reduction of phosphodiestersae-3B (PDE3B), and HSL levels, but decreased protein
      levels of perilipin A and fatty acid synthetase (FAS). The PKA inhibitor (H89)
      clearly blocked the cellular levels of perilipin A and HSL, suggesting that Pyc
      promotes lipolysis of adipocytes through activation of cAMP-dependent PKA,
      resulting in induction of HSL and reduction of perilipin A. Therefore, this study
      may elucidate the possible mechanism of Pyc, which is a candidate for weight loss
      through stimulation of lipolysis.

PMID- 25866308
TI  - Dietary soybean peptides containing a low-molecular fraction can lower serum and
      liver triglyceride levels in rats.
AB  - We investigated the effects of dietary soybean peptides, particularly low
      molecular-weight peptides, on serum and hepatic concentrations of lipids in rats.
      Soybean protein isolate (SPI) was digested with protease to produce low-molecular
      weight peptides (LD) or a mixture of high- and low-molecular-weight peptides
      (HLD). Rats were fed diets containing 20% casein, SPI, LD or HLD as a nitrogen
      source, with or without 0.5% cholesterol, for 2 wk. Next, rats were fed
      cholesterol-free diets containing 0%, 5%, 10%, or 20% LD at the expense of casein
      for 2 wk. Serum triglyceride levels were the lowest in the LD group, and liver
      triglyceride levels were significantly lower in rats fed SPI and LD/HLD diets
      than in those fed casein diets, both in the presence and absence of dietary
      cholesterol. In addition, dietary LD significantly lowered serum and liver
      triglyceride levels in a dose-dependent manner. These results suggest that low
      molecular-weight soybean peptides have a potent hypotriglyceridemic effect and
      may be beneficial for improving lipid metabolism. 

PMID- 25866309
TI  - A kinetic study of the radical-scavenging action of tocotrienols in the membranes
      of egg yolk phosphatidylcholine vesicles.
AB  - Vitamin E is localized in membranes and functions as an efficient inhibitor of
      lipid peroxidation in biological systems. In this study, we measured the second
      order rate constants (ks) for the reaction of tocotrienol homologues (alpha-,
      beta-, gamma-, and delta-Toc-3Hs) with the aroxyl radical (ArO*) used as a model
      for lipid peroxyl radicals (LOO*) in the membranes of egg yolk
      phosphatidylcholine (EYPC) vesicles by stopped-flow spectrophotometry, and
      compared them to those of tocopherol homologues (alpha-, beta-, gamma-, and delta
      TocHs). The relative rate constants of Toc-3H homologues to alpha-Toc-3H in
      membranes (alpha/beta/gamma/delta=100/83.7/63.2/20.2) were not much different to
      those of TocH homologues to alpha-TocH
      (alpha/beta/gamma/delta=100/88.4/83.8/17.3). Each ks value of Toc-3H homologues
      in membranes was 60-80% of that of the corresponding TocH homologues except for
      the almost identical ks values of delta-homologues, but there was no difference
      in EtOH solution between each ks value of the corresponding homologues of Toc-3H
      and TocH. These results indicate that the difference of the alkyl-side chain
      structure of vitamin E causes a change in the mobility of vitamin E molecules
      and/or the location of their antioxidant OH-groups in membranes, resulting in
      lowered radical-trapping rates of Toc-3Hs. By use of the ratio of the kinh value
      of alpha-TocH with LOO* (3.20*10(6) M(-1)s(-1)) to the ks value of alpha-TocH
      with ArO* (8.05*10(4) M(-1)s(-1)) in chlorobenzene (that is, 39.8), the kinh
      value for the reaction of alpha-TocH with LOO* in membrane was estimated to be
      1.03*10(5) M(-1)s(-1).

PMID- 25866310
TI  - Serum and tissue iodine concentrations in rats fed diets supplemented with kombu
      powder or potassium iodide.
AB  - Serum and tissue iodine concentration was measured in rats fed a diet
      supplemented with powdered kombu (Saccharina sculpera) or potassium iodide to
      evaluate the absorption of iodine from kombu. Eighteen male 5-wk-old Wistar rats
      were divided into three groups and fed a basal AIN93G diet (iodine content, 0.2
      mg/kg) or the basal diet supplemented with iodine (183 mg/kg) either in the form
      of kombu powder or potassium iodine (KI) for 4 wk. There were no differences in
      weight gain or serum biochemistry tests (alanine aminotransferase and aspartate
      aminotransferase activity, and total serum cholesterol and triglyceride
      concentration) after iodine supplementation. In addition, serum levels of the
      thyroid hormones thyroxine and triiodothyronine, as well as thyroid-stimulating
      hormone, were not affected. On the other hand, serum and tissue (thyroid, liver
      and kidney) iodine concentrations were markedly elevated after iodine
      supplementation. There was no difference in thyroid iodine concentration between
      KI and kombu supplementation. However, there was a significant difference
      observed in the iodine concentrations of serum, liver and kidney between the two
      iodine sources; rats fed KI had iodine concentrations in these tissues 1.8 to 1.9
      times higher than those in rats fed kombu powder. These results suggest that the
      absorption of iodine from kombu is reduced compared to that from potassium
      iodide. 

PMID- 25866311
TI  - Deoxycholic acid is involved in the proliferation and migration of vascular
      smooth muscle cells.
AB  - Obesity is increasingly becoming associated with increased risk of
      atherosclerosis. Serum levels of the bile acid deoxycholic acid (DCA) are
      elevated in mice with obesity induced by a high-fat (HF) diet. Therefore, we
      investigated the influence of DCA on the functions of vascular smooth muscle
      cells (VSMCs) because the initiation and progression of atherosclerosis are
      associated with VSMC proliferation and migration. DCA induced c-jun N-terminal
      kinase (JNK) activation whereas a JNK inhibitor prevented DCA-induced VSMC
      proliferation and migration. Based on these findings, we examined whether DCA
      promotes the expression of platelet-derived growth factor beta-receptor
      (PDGFRbeta) that has a c-Jun binding site in its promoter region. The mRNA and
      protein expression levels of PDGFRbeta were upregulated in VSMCs after a 24- and
      48-h incubation with DCA, respectively. The effects of PDGF such as proliferation
      and migration of VSMCs were promoted after a 48-h incubation with DCA despite the
      absence of DCA during PDGF stimulation. These findings suggest that elevated
      serum concentrations of DCA are involved in the pathogenesis of atherosclerosis
      in HF-induced obesity.

PMID- 25866312
TI  - The effect of vitamin E on mortality is not uniform across the population.

PMID- 25866313
TI  - Matrix normalized MALDI-TOF quantification of a fluorotelomer-based acrylate
      polymer.
AB  - The degradation of fluorotelomer-based acrylate polymers (FTACPs) has been
      hypothesized to serve as a source of the environmental contaminants,
      perfluoroalkyl carboxylates (PFCAs). Studies have relied on indirect measurement
      of presumed degradation products to evaluate the environmental fate of FTACPs;
      however, this approach leaves a degree of uncertainty. The present study
      describes the development of a quantitative matrix-assisted laser
      desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry method as the
      first direct analysis method for FTACPs. The model FTACP used in this study was
      poly(8:2 FTAC-co-HDA), a copolymer of 8:2 fluorotelomer acrylate (8:2 FTAC) and
      hexadecyl acrylate (HDA). Instead of relying on an internal standard polymer, the
      intensities of 40 poly(8:2 FTAC-co-HDA) signals (911-4612 Da) were normalized to
      the signal intensity of a matrix-sodium cluster (659 Da). We termed this value
      the normalized polymer response (P(N)). By using the same dithranol solution for
      the sample preparation of poly(8:2 FTAC-co-HDA) standards, calibration curves
      with coefficient of determinations (R(2)) typically >0.98 were produced. When
      poly(8:2 FTAC-co-HDA) samples were prepared with the same dithranol solution as
      the poly(8:2 FTAC-co-HDA) standards, quantification to within 25% of the
      theoretical concentration was achieved. This approach minimized the sample-to
      sample variability that typically plagues MALDI-TOF, and is the first method
      developed to directly quantify FTACPs.

PMID- 25866314
TI  - Prognostic implication of the loss of TGFBR2 expression in oral carcinoma.
AB  - Oral squamous cell carcinoma (OSCC) is a disease that strikes many worldwide,
      accounting for more than 145,000 deaths annually. This study examined the role of
      Transforming Growth Factor Beta (TGFbeta) signalling alterations in oral
      carcinogenesis and also its influence on the disease prognosis. In presented
      study, we evaluated the protein-level alterations of core TGFbeta signalling
      members in 20 potentially malignant oral disorders (PMDs) - leukoplakia and
      submucous fibrosis and 87 oral cancer samples by western blotting. Further, we
      analysed the association between these alterations and prognosis of oral
      carcinoma. For statistical analyses, univariate test like Student's 't'-test to
      compare expression level of various genes and logrank test has been used to
      compare the Kaplan-Meier survival curves. The multivariate model such as Cox's
      proportional hazard regression was used to verify the independent influence of
      each variable on the survival endpoints. A gradual decrease in the expression of
      TGFbeta signalling members like SMAD2, SMAD4, TGFBR1 and TGFBR2 have been noted
      from normal to PMD in oral cancers. The bio-activeforms, SMAD2/3 also showed a
      similar trend. SMAD3 protein was downregulated significantly in the PMD stage
      itself. Thus an inverse correlation was observed between expression of TGFbeta
      members and oral cancer progression.Furthermore, oral cancer patients showing
      TGFBR2 downregulation exhibited poor disease-free survival (p=0.005) and poor
      overall survival (p=0.012).Thus, assessing the TGFBR2 protein levels can serve as
      one of the prognostic marker for oral cancer.

PMID- 25866315
TI  - A multifunctional phosphorescent iridium(III) complex for specific nucleus
      staining and hypoxia monitoring.
AB  - A multifunctional phosphorescent iridium(III) complex (Ir1) for specific nucleus
      staining was synthesized and applied for monitoring the intranuclear oxygen
      level. With the advantageous long emission lifetime of Ir1, the influence of
      autofluorescence could be eliminated by using photoluminescence lifetime imaging
      and time-gated luminescence imaging techniques.

PMID- 25866317
TI  - Extended piperidine-piperidinone protein interface mimics.
AB  - Minimalist structures, H and I, were designed as protein interface mimics.
      Attributes of these chemotypes are (i) greater rigidity than conventional
      peptides, (ii) chiral and nonplanar heterocyclic backbones that are less prone to
      the hydrophobic aggregation effects, and (iii) potential to be prepared with a
      variety of side chains corresponding to natural amino acids. Intermediates,
      however, in the oligo(pyrrolidinone-piperidine)s H syntheses were vulnerable to
      epimerization. The origins of this epimerization were determined, then the study
      was focused on oligo(piperidinone-piperidine) compounds I. Mimics I were prepared
      via iterative couplings; a penta(piperidinone-piperidine) was prepared in this
      way. A series of lower homologues of this pentamer were crystallized and studied
      (single crystal X-ray), and four of them were used in a circular dichroism (CD)
      study. Thus, an estimate of 36 A for the N-to-C distance of a typical
      conformation of the penta(piperidinone-piperidine) was made. CD spectra of four
      progressively longer oligomers allowed assignment of elipticity changes around
      300 nm that can be attributed to increased conformational ordering of the longer
      oligomers in solution. 

PMID- 25866316
TI  - A validated LC-MS/MS assay for quantification of 24(S)-hydroxycholesterol in
      plasma and cerebrospinal fluid.
AB  - 24(S)-hydroxycholesterol [24(S)-HC] is a cholesterol metabolite that is formed
      almost exclusively in the brain. The concentrations of 24(S)-HC in cerebrospinal
      fluid (CSF) and/or plasma might be a sensitive marker of altered cholesterol
      metabolism in the CNS. A highly sensitive 2D-LC-MS/MS assay was developed for the
      quantification of 24(S)-HC in human plasma and CSF. In the development of an
      assay for 24(S)-HC in CSF, significant nonspecific binding of 24(S)-HC was
      observed and resolved with the addition of 2.5% 2-hydroxypropyl-beta-cyclodextrin
      (HP-beta-CD) into CSF samples. The sample preparation consists of liquid-liquid
      extraction with methyl-tert-butyl ether and derivatization with nicotinic acid.
      Good linearity was observed in a range from 1 to 200 ng/ml and from 0.025 to 5
      ng/ml, for plasma and CSF, respectively. Acceptable precision and accuracy were
      obtained for concentrations over the calibration curve ranges. Stability of 24(S)
      HC was reported under a variety of storage conditions. This method has been
      successfully applied to support a National Institutes of Health-sponsored
      clinical trial of HP-beta-CD in Niemann-Pick type C1 patients, in which 24(S)-HC
      is used as a pharmacodynamic biomarker. 

PMID- 25866318
TI  - The obesity paradox and survivors of ischemic stroke.
AB  - BACKGROUND: Although obesity is a risk factor for stroke and achieving normal
      weight is advocated to decrease stroke risk, the risk associated with obesity and
      weight loss after stroke has not been well established. The aim of this study was
      to assess the association of obesity at the time of stroke admission and weight
      loss after stroke with total mortality. METHODS: We analyzed 736 consecutive
      patients (mean age, 66 +/- 11 years; 58% men) hospitalized for their first
      ischemic stroke. Body weight at hospital admission and at the outpatient visit
      during follow-up was used in the analysis. RESULTS: After multivariate
      adjustment, obesity at admission was associated with lower mortality risk as
      compared with normal weight (hazard ratio [HR], .50, P = .03). At the outpatient
      visit, with a median follow-up time of 16 months, 21% of patients had lost more
      than 3 kg of weight. Stroke severity, heart failure, transient ischemic attack,
      and depression after stroke were independently associated with significant weight
      loss. Weight loss of more than 3 kg was associated with increased mortality risk
      (HR, 5.87; P = .001) independently of other factors. Similar results were seen
      when weight loss was defined as losing more than 3% of baseline weight (HR, 4.97;
      P = .004). Weight gain of more than 5% of the baseline weight tended to be
      associated with better survival when compared with no weight change (log-rank
      test, P = .07). CONCLUSIONS: Normal weight at hospital admission and weight loss
      after ischemic stroke are independently associated with increased mortality.
      Overweight and obesity at baseline do not decrease the risk associated with
      weight loss.

PMID- 25866319
TI  - Factors associated with the presentation of moyamoya in childhood.
AB  - BACKGROUND: Moyamoya accounts for approximately one fifth of cerebral
      arteriopathies in children presenting with acute stroke; however, often is not
      diagnosed until stroke occurs, even in higher risk populations and often despite
      a history of transient ischemic attacks (TIAs). This study was undertaken to
      better define which groups of children are at risk for moyamoya and how they
      present. METHODS: With institutional review board approval, the charts of all
      patients with a diagnosis of moyamoya were reviewed. RESULTS: Fifty-four patients
      were identified. Mean age at presentation was 7.5 years; 56% were female; 32
      (59%) had predisposing medical conditions associated with moyamoya; and 17 (31%)
      were of Asian descent. Only 11 children (20%) had no underlying predisposing
      condition identified, of whom, 4 had underlying conditions not previously
      reported in association with moyamoya. Eight patients (15%) were Native American;
      38 (70%) had a history of TIAs; and 26 (48%) presented with acute stroke, of
      whom, three fourth had left and one fourth had right hemisphere strokes. Fifty
      two percent had a history of headache. CONCLUSIONS: Most children with moyamoya
      in this series had an underlying predisposing condition, compared with other US
      series, where almost half had no predisposing condition identified. In this
      series, fewer children (48% versus 68%) presented with stroke, many (70% versus
      43%) had a history of TIAs, and many (52% versus 22%) had a history of headaches
      than in previous reports. In addition, the Native American population may be at
      higher risk of moyamoya than previously recognized.

PMID- 25866320
TI  - Diffusion Tensor Imaging in brain tumors: A study on gliomas and metastases.
AB  - PURPOSE: To explore the role of Diffusion Tensor Imaging in preoperative glioma
      grading, as well as in differentiation between gliomas and metastatic brain
      tumors. We measured diffusion tensor variables in enhancement and edema regions,
      which were compared between the different subject groups. MATERIALS AND METHODS:
      We performed DTI in 48 patients (11 Low Grade Gliomas, 27 High Grade Gliomas, 10
      Single Metastatic brain tumors). We measured FA, lambda1, lambda2, lambda3, ADC,
      Cl, Cp, Cs, RA, and VR in enhancing portions of tumors and edema regions.
      Additionally, ratios of enhancement to edema values were created for each
      variable. RESULTS: In peritumoral edema, Cl and RA were proven to be
      significantly different in pair-wise comparisons, in addition to ADC, Cp, Cs and
      VR in enhancement regions. Enhancement to edema values were significantly
      different as well. CONCLUSION: Diffusion tensor indices could be used for the
      differentiation between low and high grade gliomas, as well as for distinction
      between gliomas and metastases.

PMID- 25866321
TI  - Ankle dorsiflexion may play an important role in falls in women with
      fibromyalgia.
AB  - BACKGROUND: Fibromyalgia is a chronic pain condition, which involves reduced
      range of motion. This leads to gait changes and high incidence of falls. The
      understanding of the gait patterns in subjects with fibromyalgia and their
      relationship with falls may be useful when designing intervention programs. The
      purpose of this study was to evaluate the range of motion of the hip and ankle
      joints during gait in women with and without fibromyalgia. Further, we determined
      the relationship between joint range of motion and falls in this population.
      METHODS: Middle-aged women (16 with fibromyalgia and 16 as control group) were
      recruited. Pain intensity, physical activity level, and fall prevalence were
      assessed. Three dimensional gait analysis provided temporal and joint kinematic
      variables. FINDINGS: In general, hip and ankle range of motion were similar
      between groups, except that fibromyalgia group showed higher plantar flexion
      during toe-off (P<0.05) and reduced dorsiflexion during stance phase (P<0.05).
      Additionally, in the fibromyalgia group the higher number of falls was correlated
      to reduced dorsiflexion during stance phase. This limitation in dorsiflexion was
      related to longer length of time with fibromyalgia symptoms. INTERPRETATION:
      Women with fibromyalgia showed a higher number of falls, reduced dorsiflexion
      during stance phase, and increased plantar flexion during toe-off. Also, the
      higher number of falls reported in the fibromyalgia group was related to reduced
      dorsiflexion during stance phase, which was correlated to a longer length of time
      living with fibromyalgia symptoms. These data suggest that improving ankle
      kinematics in patients with fibromyalgia may help prevent falls and improve
      mobility.

PMID- 25866322
TI  - Engineering noble metal nanomaterials for environmental applications.
AB  - Besides being valuable assets in our daily lives, noble metals (namely, gold,
      silver, and platinum) also feature many intriguing physical and chemical
      properties when their sizes are reduced to the nano- or even subnano-scale; such
      assets may significantly increase the values of the noble metals as functional
      materials for tackling important societal issues related to human health and the
      environment. Among which, designing/engineering of noble metal nanomaterials
      (NMNs) to address challenging issues in the environment has attracted recent
      interest in the community. In general, the use of NMNs for environmental
      applications is highly dependent on the physical and chemical properties of NMNs.
      Such properties can be readily controlled by tailoring the attributes of NMNs,
      including their size, shape, composition, and surface. In this feature article,
      we discuss recent progress in the rational design and engineering of NMNs with
      particular focus on their applications in the field of environmental sensing and
      catalysis. The development of functional NMNs for environmental applications is
      highly interdisciplinary, which requires concerted efforts from the communities
      of materials science, chemistry, engineering, and environmental science. 

PMID- 25866323
TI  - Costs of treatment for elderly women with advanced ovarian cancer in a Medicare
      population.
AB  - OBJECTIVE: To analyze the cost of treating women with advanced stage epithelial
      ovarian cancer (EOC) undergoing primary debulking surgery (PDS) or neo-adjuvant
      chemotherapy (NACT). METHODS: The Surveillance, Epidemiology, and End Results
      (SEER) - Medicare database (1992 to 2009) was used to evaluate the 7-month cost
      of care following PDS and NACT for advanced EOC. Multivariate analyses were used
      to evaluate differences between women treated by PDS and NACT on cost and
      survival. RESULTS: Of the 4506 women eligible for analysis, 82.4% underwent PDS
      and 17.6% received NACT. Eighty-five percent with stage IIIC and 78.5% with stage
      IV EOC underwent PDS (p<0.0001). No significant difference in the median cost of
      care between PDS and NACT existed in women with stage IIIC EOC ($59,801 vs.
      $59,905). There was a 12% increase in adjusted cost of care for stage IV patients
      ($63,131 vs. $55,302) who received PDS (p<0.0001). Increasing Charlson score was
      associated with an increase in 7-month cost of care in both stages. NACT was
      associated with a decreased 5-year overall survival in women with stage IIIC EOC
      (HR=1.27, 95% CI: 1.10-1.47) and stage IV EOC (HR=1.19, 95% CI: 1.03-1.37)
      compared to PDS. CONCLUSION: NACT and PDS are comparable in cost for women with
      stage IIIC EOC, and PDS is minimally more expensive for women with stage IV EOC.
      PDS was associated with an increase 5-year overall survival. Future
      investigations should include cost-effectiveness analyses where additional
      measures such as quality adjusted life years and propensity scored survival are
      included.

PMID- 25866324
TI  - Detection of the HE4 protein in urine as a biomarker for ovarian neoplasms:
      Clinical correlates.
AB  - OBJECTIVES: To measure HE4 levels in urine from normal donors, patients with LMP
      tumors and ovarian cancer patients and to correlate levels with clinical factors
      in ovarian cancer patients. METHODS: Archived samples from controls, patients
      with LMP tumors and ovarian cancer were tested using commercial assays, including
      serially collected serum and urine samples from women treated for stage III/IV
      serous ovarian cancer. RESULTS: Five of 6 patients with stage I/II and 26 of 36
      stage III/IV serous ovarian cancer patients had HE4-positive urines, similar to
      serum samples (4 of 5 stage I/II and 26 of 34 stage III/IV) when tested at the
      same level of specificity (95%). Urine HE4 was more sensitive in LMP tumors: 9 of
      32 urines (28%) HE4-positive versus 3 of 68 sera (4.4%, p=0.002). Mean levels of
      serum CA125 and HE4 decreased comparably in patients during initial treatment
      regardless of their primary platinum response, but mean urine HE4 levels
      decreased only 7% in primary platinum resistant patients while decreasing 68% in
      those who were sensitive. By 7months after diagnosis, urine HE4 levels were
      higher in primary platinum resistant patients compared to those who proved to be
      sensitive (p=0.051) and persisted 12months after diagnosis (p=0.014). HE4 values
      in urine also became positive in advance of clinical recurrence in several women
      while serum HE4 and serum CA-125 remained normal. CONCLUSIONS: Measuring HE4 in
      urine complements serum assays for the detection of ovarian cancer and may allow
      identification of patients at high risk for primary platinum resistance.

PMID- 25866325
TI  - Improving arteriovenous fistula patency: Transdermal delivery of diclofenac
      reduces cannulation-dependent neointimal hyperplasia via AMPK activation.
AB  - Creation of an autologous arteriovenous fistula (AVF) for vascular access in
      haemodialysis is the modality of choice. However neointimal hyperplasia and loss
      of the luminal compartment result in AVF patency rates of ~60% at 12months. The
      exact cause of neointimal hyperplasia in the AVF is poorly understood. Vascular
      trauma has long been associated with hyperplasia. With this in mind in our rabbit
      model of AVF we simulated cannulation autologous to that undertaken in vascular
      access procedures and observed significant neointimal hyperplasia as a direct
      consequence of cannulation. The neointimal hyperplasia was completely inhibited
      by topical transdermal delivery of the non-steroidal anti-inflammatory (NSAID)
      diclofenac. In addition to the well documented anti-inflammatory properties we
      have identified novel anti-proliferative mechanisms demonstrating diclofenac
      increases AMPK-dependent signalling and reduced expression of the cell cycle
      protein cyclin D1. In summary prophylactic transdermal delivery of diclofenac to
      the sight of AVF cannulation prevents adverse neointimal hyperplasic remodelling
      and potentially offers a novel treatment option that may help prolong AVF patency
      and flow rates. 

PMID- 25866326
TI  - Clinical and pathological characteristics of 5 children with HBV surface antigen
      (HBsAg)-negative hepatitis B virus-associated glomerulonephritis.
AB  - BACKGROUND: Hepatitis B virus-associated glomerulonephritis (HBV-GN) mainly
      occurs in children. Patients with HBV-GN are frequently positive for serum HBV
      surface antigen (HBsAg), but they are rarely negative. OBJECTIVE: To explore the
      clinical and pathological characteristics of patients with HBV-GN who are serum
      HBsAg negative. STUDY DESIGN: Five children with HBV-GN who are negative for
      HBsAg were included in this study. Their clinical and pathological
      characteristics were collected and analyzed. RESULTS: All 5 children presented
      with different levels of proteinuria and microscopic hematuria. Renal biopsies
      showed membranous nephropathy accompanied by HBsAg and/or HBcAg deposits in
      glomeruli in all of the children. Steroids and/or other immunosuppressants were
      administered in all cases without antiviral therapy during the early stages of
      treatment. Two children achieved complete remission but relapsed after the drugs
      were tapered down. The other 3 children were initially non-responsive but
      achieved remission after lamivudine was added. CONCLUSIONS: Treatment of HBsAg
      negative HBV-GN patients with immunosuppressants alone could not achieve
      satisfactory effects. Antiviral treatment is effective and may be necessary in
      this type of patient.

PMID- 25866327
TI  - Direct multiplexed whole genome sequencing of respiratory tract samples reveals
      full viral genomic information.
AB  - BACKGROUND: Acute respiratory tract infections (RTI) cause substantial morbidity
      during childhood, and are responsible for the majority of pediatric infectious
      diseases. Although most acute RTI are thought to be of viral origin, viral
      etiology is still unknown in a significant number of cases. OBJECTIVES:
      Multiplexed whole genome sequencing (WGS) was used for virome determination
      directly on clinical samples as proof of principle for the use of deep sequencing
      techniques in clinical diagnosis of viral infections. STUDY DESIGN: WGS was
      performed with nucleic acids from sputum and nasopharyngeal aspirates from four
      pediatric patients with known respiratory tract infections (two patients with
      human rhinovirus, one patient with human metapneumovirus and one patient with
      respiratory syncytial virus), and from four pediatric patients with PCR-negative
      RTI, and two control samples. RESULTS: Viral infections detected by routine
      molecular diagnostic methods were confirmed by WGS; in addition, typing
      information of the different viruses was generated. In three out of four samples
      from pediatric patients with PCR-negative respiratory tract infections and the
      two control samples, no causative viral pathogens could be detected. In one
      sample from a patient with PCR-negative RTI, rhinovirus type-C was detected.
      Almost complete viral genomes could be assembled and in all cases virus species
      could be determined. CONCLUSIONS: Our study shows that, in a single run, viral
      pathogens can be detected and characterized, providing information for clinical
      assessment and epidemiological studies. We conclude that WGS is a powerful tool
      in clinical virology that delivers comprehensive information on the viral content
      of clinical samples.

PMID- 25866328
TI  - A case of Alkhumra virus infection.
AB  - Alkhumra virus (ALKV) is an emerging tick-borne flavivirus known to cause a
      neglected tropical disease in the Middle East. The magnitude of the disease among
      European returning travelers is still unknown probably because the inadequate
      knowledge about the real geographic distribution of ALKV infection have limited
      its diagnosis. Up to now in Italy were reported only three cases; here we report
      the fourth case of ALKV in a returning traveler from south Egypt. 

PMID- 25866329
TI  - Performance of ARCHITECT HCV core antigen test with specimens from US plasma
      donors and injecting drug users.
AB  - BACKGROUND: Hepatitis C virus (HCV) core antigen is a serological marker of
      current HCV infection. OBJECTIVES: The aim of this study was mainly to evaluate
      the performance characteristics of the ARCHITECT HCV core antigen assay with
      specimens from US plasma donors and injecting drug users. STUDY DESIGN: A total
      of 551 serum and plasma samples with known anti-HCV and HCV RNA status were
      tested for HCV core antigen using the Abbott ARCHITECT HCV core antigen test.
      RESULTS: HCV core antigen was detectable in 100% of US plasma donor samples
      collected during the pre-seroconversion phase of infection (anti-HCV negative/HCV
      RNA positive). Overall sensitivity of the HCV core antigen assay was 88.9-94.3%
      in samples collected after seroconversion. The correlation between HCV core
      antigen and HCV RNA titers was 0.959. CONCLUSIONS: HCV core antigen testing may
      be reliably used to identify current HCV infection.

PMID- 25866330
TI  - The prevalence of STL polyomavirus in stool samples from Chinese children.
AB  - BACKGROUND: Over the past 7 years, eleven novel human polyomaviruses (HPyVs) have
      been identified. The frequent discovery of human polyomaviruses (HPyVs) in the
      gastrointestinal tract and stool samples suggests a potential involvement in
      gastroenteritis. OBJECTIVE: In this study we want to explore the prevalence of
      STL polyomavirus (STLPyV) in China and delineate the clinical role played by
      STLPyV. STUDY DESIGN: Stool samples from 508 hospitalized children with diarrhea
      and 271 healthy children were screened to detect STLPyV. Human polyomavirus
      12(HPyV12), New Jersey polyomavirus (NJPyV-2013) and six common enteric viruses
      (including rotaviruses, adenovirus, norovirus GI and GII, astrovirus and
      sapovirus) were also screened in this study. RESULTS: 348 of the 508 (68.5%)
      specimens from the hospitalized children with diarrhea contained at least 1
      common enteric virus. STLPyV was identified in 11 specimens in the case group
      (2.2%), among which 4 specimens were negative for those common enteric viruses.
      STLPyV was not more prevalent among the case group than the control group (2.2%
      versus 3.0%; p = 0.50, chi(2) test). In case group, when common enteric viruses'
      positive and negative groups were compared, the difference in detection rate of
      STLPyV was not statistically significant (2.5% versus 2.0%; p = 0.98, chi(2)
      test). Two whole genome sequences of STLPyV were obtained. CONCLUSIONS: We are
      the first to report the prevalence of STLPyV in Chinese children and obtained
      whole genome sequences of STLPyV strains isolated in China. Our results of
      phylogenetic analysis support the hypothesis that STLPyV is geographically
      widespread.

PMID- 25866331
TI  - A Dengue virus serotype 4-dominated outbreak in central Vietnam, 2013.

PMID- 25866332
TI  - Molecular epidemiology and molecular characterization of respiratory syncytial
      viruses at a tertiary care university hospital in Catalonia (Spain) during the
      2013-2014 season.
AB  - BACKGROUND: Human respiratory syncytial virus (HRSV) is the main cause of lower
      respiratory tract infections among infants and young children. OBJECTIVES: The
      molecular epidemiology and characterization of HRSV strains detected at a Spanish
      tertiary hospital during the 2013-2014 season is reported. STUDY DESIGN:
      Phylogenetic analysis and molecular characterization of HRSV laboratory-confirmed
      respiratory samples were performed, based on coding sequences of G and F
      proteins. RESULTS: HRSV infection was laboratory-confirmed in respiratory samples
      from 320 patients of which 223 (70%) were less than 2 years of age and none
      undergoing Palivizumab treatment. HRSV was detected at varying levels throughout
      the season with a maximum rate in the week 52/2013, right before the beginning of
      the influenza epidemic. Whilst both HRSV groups were found co-circulating, HRSV-B
      group clearly predominated. The phylogenetic analyses from 139 HVR-2 sequences
      revealed that most characterized strains belonged to ON1 and BA9 genotypes. Three
      different phylogenetic subgroups could be distinguished within these genotypes.
      In addition, three strains (out of the 52 randomly selected) were carrying amino
      acid substitutions in the epitope A of the F protein, one of them previously
      related to Palivizumab resistance. CONCLUSIONS: The results of the present study
      highlight the importance of a continuous HRSV surveillance to monitor not only
      the introduction of new genotypes on circulation but also the emergence of viral
      variants with new genetic characteristics that can affect the antigenicity
      features and the susceptibility to the only current prophylaxis treatment and
      also for the future development of HRSV vaccines.

PMID- 25866333
TI  - Hepatitis delta virus testing, epidemiology and management: a multicentre cross
      sectional study of patients in London.
AB  - BACKGROUND: Hepatitis delta virus (HDV) testing is recommended for all patients
      with hepatitis B virus (HBV) infection. HDV infection is associated with severe
      liver disease and interferon is the only available treatment. OBJECTIVES: To
      determine the rate of anti-HDV antibody testing in HBV patients; and to describe
      the epidemiology, clinical characteristics and management of HDV-infected
      patients at four hospitals in London. STUDY DESIGN: The anti-HDV testing rate was
      estimated by reviewing clinical and laboratory data. Cross-sectional data
      collection identified HDV-infected patients who had attended the study centres
      between 2005 and 2012. RESULTS: At a centre with clinic-led anti-HDV testing, 40%
      (67/168) of HBV patients were tested. Recently diagnosed HBV patients were more
      likely to be screened than those under long-term follow-up (62% vs 36%, P=0.01).
      At a centre with reflex laboratory testing, 99.4% (3543/3563) of first hepatitis
      B surface antigen positive samples were tested for anti-HDV. Across the four
      study centres there were 55 HDV-infected patients, of whom 50 (91%) had
      immigrated to the UK and 27 (49%) had evidence of cirrhosis. 31 patients received
      interferon therapy for HDV with an end of treatment virological response observed
      in 10 (32%). CONCLUSIONS: The anti-HDV testing rate was low in a centre with
      clinic-led testing, but could not be evaluated in all centres. The HDV-infected
      patients were of diverse ethnicity, with extensive histological evidence of liver
      disease and poor therapeutic responses. Future recommendations include reflex
      laboratory testing algorithms and a prospective cohort study to optimise the
      investigation and management of these patients.

PMID- 25866334
TI  - Dynamics of HCV genotype 4 resistance-associated variants during virologic escape
      with pIFN/RBV+daclatasvir: a case study using ultra deep pyrosequencing.
AB  - BACKGROUND: Daclatasvir (DCV) is an approved NS5A inhibitor with potent anti-HCV
      activity and broad genotype coverage. DCV resistance-associated variants (RAVs)
      have been described for patients infected with genotype (GT) 1, but increased GT4
      prevalence in European countries as a result of immigration has boosted interest
      in this genotype. OBJECTIVES: Establishment of NS5A variability in treatment
      naive patients with HCV genotype 4 infection and a case study of the dynamics of
      resistance-associated variants in a virologic failure receiving pIFN/RBV+DCV, as
      assessed by ultra-deep sequencing. STUDY DESIGN: Five treatment-naive GT4
      patients (GT4a [n = 1], GT4d [n = 3], GT4o [n = 1]) were evaluated for inclusion
      in the COMMAND-4 study and treatment with pIFN/RBV+/-DCV. RESULTS: Patient (Pt) 1
      received pIFN/RBV; Pts2-4 received pIFN/RBV + DCV; Pt5 was a screening failure.
      Pt1 relapsed; Pt2 experienced breakthrough at Wk4; Pts3 and 4 achieved a
      sustained virologic response. No substitutions associated with DCV-resistance
      were detected at baseline. In terms of viremic time points for Pts1 and 2, the
      extent of NS5A diversity pre-treatment was not significantly related to viral
      load (r = -0568; p = 0.035). In Pt2, multiple substitutions associated with DCV
      resistance were observed after breakthrough at NS5A amino acid positions 28, 31
      and 93. These substitutions were frequently observed on the same haplotype (L28S
      + M31I = 55.52, 82.50, and 99.36% at Wk4, 8 and 9; L28S + M31I + Y93H = 11.77,
      5.01 and <0.6% at Wk4, 8 and 9). CONCLUSIONS: This is the first report to
      describe DCV-resistance in patients infected with GT4d, supporting a possible
      role for a recently described RAV (L28S), and presenting the dynamics of HCV
      quasispecies during therapy failure, with indications of changes of diversity and
      association of mutations.

PMID- 25866335
TI  - Rapid increase in the serum Cytomegalovirus IgG avidity index in women with a
      congenitally infected fetus.
AB  - BACKGROUND: Human Cytomegalovirus (CMV) is the virus most frequently responsible
      for severe diseases of the fetus and newborn. The reported intrauterine
      transmission rate of CMV following primary maternal infection is approximately
      40%. Invasive techniques are needed for the prenatal diagnosis of congenital CMV
      infection. OBJECTIVES: The aim of this study was to evaluate whether the rapidity
      of change in the CMV IgG avidity index (AI) is associated with the presence of
      congenital CMV infection among mothers with suspected primary CMV infection.
      STUDY DESIGN: The serum CMV IgG AI was repeatedly measured in 17 pregnant women
      with positive or borderline test results for CMV IgM together with an initial IgG
      AI value of <40%. Their neonates underwent polymerase chain reaction analyses for
      the presence of CMV DNA in the urine. The rapidity of change in the IgG AI per 4
      weeks was defined as the DeltaAI (%). The DeltaAI of women with congenital CMV
      infection was compared with that of women with no infection. RESULTS: The DeltaAI
      of nine mothers with congenital CMV infection (median,15.7%; range,7.8-42.8%) was
      significantly higher than that of eight mothers with no infection (median, 6.5%,
      range, 2.0-8.8%; p<0.001). The incidences of congenital CMV infection were
      100.0%, 16.7%, and 0.0% among mothers with a DeltaAI of >10, 5-10, and <5%,
      respectively. CONCLUSIONS: Measurement of the DeltaAI in pregnant women might be
      useful for estimating the risk of mother-to-neonate CMV transmission.

PMID- 25866336
TI  - Cytomegalovirus appendicitis in solid organ transplant patients, two cases and a
      review.
AB  - Cytomegalovirus (CMV) disease is a common complication following solid organ
      transplantation with a variety of gastrointestinal (GI) tract manifestations. CMV
      appendicitis, however, is a rare complication in a solid organ transplant
      patient, having been reported only once previously. We have recently seen two
      cases in solid organ transplant recipients at our institution, one a liver
      recipient and the other a heart recipient. Both patients underwent surgical
      resection. Pathologic evaluation of both resected appendices as well as
      polymerase chain reaction (PCR) amplification for CMV from the serum revealed the
      virus as the etiology. Both patients received induction intravenous ganciclovir
      followed by oral valganciclovir and have done well post-operatively. Tissue
      invasive CMV disease should be considered in the differential diagnosis for solid
      organ transplant patients with symptoms suggesting acute or chronic appendicitis.
      Both PCR testing as well as pathologic review of tissue specimens should be
      considered to ensure accurate diagnosis and management. 

PMID- 25866337
TI  - Field study of fecal excretion as a decision support tool in response to silent
      reintroduction of wild-type poliovirus 1 into Israel.
AB  - BACKGROUND: Israel has used an inactivated polio vaccine (IPV)-only schedule
      since 2005 (95% coverage). Silent reintroduction of wild type poliovirus 1 (WPV1)
      into Israel in early 2013 was detected in Southern Israel via routine
      environmental surveillance without clinical cases. OBJECTIVES: To estimate the
      rate of WPV1 excretion by age and residence and inform decision-making regarding
      supplemental immunization with OPV. STUDY DESIGN: A convenience sample of Bedouin
      and Jewish residential areas in the epicenter of the incident, focusing on under
      8 year-olds who not previously given OPV. Fecal samples were directly tested for
      WPV1 RNA using a novel qRT-PCR assay. Positive samples were confirmed by gold
      standard cell culture and subject to genotyping. RESULTS: Overall, 2196 non
      duplicate fecal samples were collected and analyzed. WPV1 was detected in 61
      samples (2.8%), 55 of which (90.2%) were from Bedouins. WPV1 excretion rates were
      5.4% among Bedouins and 0.6% among Jewish individuals. Respective age-specific
      rates among Bedouin and Jewish children were 4.9% and 0.2% for 0-2 years and 7.2%
      and 1.7% for 2-8 years. Molecular testing had 89.5% sensitivity (higher than
      culture) and 100% specificity. CONCLUSION: The rapid performance of a field study
      to evaluate WPV1 excretion unequivocally demonstrated substantial WPV1 infection
      rates among children under 8 years in Southern Israel, thus informing the
      decision to vaccinate this age group with bOPV and risk communication to both
      healthcare personnel and the public. Rapid development and implementation of
      molecular screening can thus underpin risk assessment and management in complex
      epidemiological situations.

PMID- 25866338
TI  - Evaluation of sequencing of HCV core/E1, NS5A and NS5B as a genotype predictive
      tool in comparison with commercial assays targeting 5'UTR.
AB  - BACKGROUND: Hepatitis C virus (HCV) genotyping is required for tailoring the dose
      and duration of antiviral therapy, predicting virological response rates, and
      selecting future treatment options. OBJECTIVE: To establish whether baseline
      genotypes, performed by INNO-LiPA Version 1.0 (v1.0), before 2008, were valid for
      making treatment decisions now or whether genotypic determination should be
      repeated. Furthermore, to evaluate concordance between Abbott RealTime genotype
      II assay (RT) and genotyping by sequencing HCV C/E1, NS5A, NS5B. STUDY DESIGN:
      Genotyping by RT and sequencing was performed on paired historic and current
      specimens from 50 patients previously baseline genotyped using INNO-LiPA.
      RESULTS: Of 100 samples from 50 patients, >= 2 of HCV genomic target regions
      yielded a sequence that was suitable for genotyping, with 100% concordance,
      providing no evidence of recombination events. Genotype and subtype prediction
      based on RT and sequencing agreed in 62.8% historic and 72.7% current specimens,
      with a kappa coefficient score of 0.48 and 0.76, respectively. LiPA could not
      subtype 46% of HCV gt1 infections, and LiPA subgenotype was only in agreement
      with RT and sequencing in 28.6% cases, where matched baseline and historic
      specimens were available. Three patients were indeterminate by RT, and five
      patients with HCV gt1 infections could not be subtyped by RT. However, RT
      revealed mixed infections in five patients where sequencing detected only single
      HCV infection at 20% threshold. CONCLUSION: Genotyping by sequencing, exhibited
      excellent concordance, with moderate to good agreement with RT, and could resolve
      RT indeterminates and subtype HCV-gt1 infections not possible by LiPA.

PMID- 25866339
TI  - Venezuela: far from the path to dengue and chikungunya control.

PMID- 25866340
TI  - High positivity of mimivirus in inanimate surfaces of a hospital respiratory
      isolation facility, Brazil.
AB  - BACKGROUND: Mimiviruses have been considered putative emerging pneumonia agents.
      Pneumonia is a leading cause of death related to infection throughout the world,
      with approximately 40% of cases presenting unknown etiology. Therefore,
      identifying new causative agents of community and nosocomial pneumonia is of
      major public health concern. OBJECTIVE: We evaluated the distribution of these
      viruses in samples collected from different environments of one of the largest
      hospitals in Brazilian Southeast. STUDY DESIGN: We analyzed, by molecular and
      virological approaches, the distribution of mimivirus in 242 samples collected
      from inanimate surfaces in different hospital facilities. RESULTS: A significant
      positivity of mimivirus in respiratory-isolation-facilities was observed
      (p<0.001). CONCLUSION: Although the role of mimivirus as etiological agents of
      pneumonia is still under investigation, our results demonstrates interesting
      correlations that strengthens the need for control over the occurrence of these
      viruses in hospital facilities.

PMID- 25866341
TI  - Human papillomavirus type 16 L1/L2 DNA methylation shows weak association with
      cervical disease grade in young women.
AB  - BACKGROUND: Persistent infection with human papillomavirus (HPV) type 16 causes
      the majority of cervical cancers. Genital HPV infection is very common, but
      neoplastic progression is uncommon. There is an urgent need for biomarkers
      associated with cervical neoplasia, to enable triage of women who test positive
      for HPV. OBJECTIVES: To assess the ability of quantitative measurement of HPV16
      DNA methylation to separate samples of different cytological and histological
      grades from young women, among whom rates of HPV infection are high. STUDY
      DESIGN: DNA methylation was quantified by pyrosequencing of bisulphite converted
      DNA from liquid based cytology samples from 234 women (mean age 20.6 years) who
      tested positive for HPV16 and showed varying degrees of neoplasia. Methylation
      was assessed at CpGs in the HPV E2 and L1/L2 regions. RESULTS: The performance of
      methylation-based classifiers was assessed by ROC curve analyses. The best
      combination of CpGs (5600 and 5609) achieved AUCs of 0.656 (95% CI=0.520-0.792)
      for separation of cytologically normal and severely dyskaryotic samples, and
      0.639 (95% CI=0.547-0.731) for separation of samples with or without high-grade
      neoplasia (CIN2+/-). CONCLUSIONS: The data are consistent with HPV L1/L2
      methylation being a marker of the duration of infection in a specific host.
      Assessment of HPV DNA methylation is hence a promising biomarker to triage HPV
      positive cytology samples, but may have limited utility in young women. Future
      studies assessing the likely utility of HPV DNA methylation as a potential triage
      biomarker must take account of women's age.

PMID- 25866342
TI  - Disseminated VZV infection and asymptomatic VZV vasculopathy after steroid abuse.
AB  - A 60-year-old man who abused corticosteroids developed thoracic-distribution
      zoster. Varicella zoster virus (VZV) DNA was found in non-healing skin 3 months
      later. He died suddenly 2 months later. Skin was ulcerated and necrotic. VZV was
      widespread in organs and arteries, particularly coronary arteries and aorta, with
      VZV vasculopathy in the posterior cerebral artery. 

PMID- 25866343
TI  - Elevated chemokine levels during adult but not pediatric Crimean-Congo
      hemorrhagic fever.
AB  - BACKGROUND: Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne viral
      zoonosis. Clinical reports indicate the severity of CCHF is milder in children
      than adults. The chemokines are important chemo-attractant mediators of the host
      immune system. OBJECTIVES: The main aim of the study was to identify whether or
      not there were any differences in chemokine levels between the pediatric and
      adult patients and control groups, and whether there was any correlation with
      disease severity. STUDY DESIGN: The serum levels of select chemokines including
      chemokine (C-C) ligand 2 (CCL2), CCL3, CCL4, chemokine (C-X-C) ligand 8 (CXCL8),
      CXCL9, and granulocyte-colony stimulating factor (G-CSF) in 29 adult and 32
      pediatric CCHF patients and in 35 healthy children and 40 healthy adult control
      groups were studied by flow cytometric bead immunoassay method. RESULTS: Great
      variability was detected in the serum levels of the chemokines for both the adult
      and pediatric patients and controls. With the exception of G-CSF, the median
      serum levels of CCL2, CCL3, CCL4, CXCL8, and CXCL9 were found to be significantly
      higher in the adult patients compared to adult controls (2364.7 vs. 761 pg/ml;
      714.1 vs. 75.2 pg/ml; 88.6 vs. 25.5 pg/ml; 217.9 vs. 18.3 pg/ml; 875 vs. 352.2
      pg/ml, respectively, p < 0.0001 for all comparisons). Among the chemokines the
      median CCL4 and G-CSF levels were significantly higher in the pediatric patients
      compared to pediatric controls (40.3 vs. 7.1 pg/ml, p < 0.0001; 0.1 vs. 0.1
      pg/ml, p = 0.049, respectively). CONCLUSION: The results of this study showed
      prominent chemokine raising in adult CCHF patients compared to children CCHF
      patients.

PMID- 25866344
TI  - Prospective evaluation of rhinovirus infection in healthy young children.
AB  - BACKGROUND: Although the incidence of human rhinovirus (HRV) infection is highest
      in young, no study has yet been published concerning the types of HRV circulating
      in this population, the incidence of symptomatic infections due to the different
      types, or duration of shedding OBJECTIVES: This prospective study evaluated the
      circulation of HRV species and types, and established the incidence of
      asymptomatic and symptomatic infections in young children. STUDY DESIGN: The
      study enrolled 93 healthy children aged <2 years, 88 of whom completed the follow
      up of weekly household visits from November 2013 to February 2014. At each visit,
      a record was made of any signs and symptoms of acute infection, and a
      nasopharyngeal (NP) swab was taken in order to identify the HRVs by means of RT
      polymerase chain reaction and to construct the phylogenetic tree of the HRV
      positive cases. RESULTS: A total of 1408 NP samples were obtained and 326 HRV
      infections were diagnosed (23.1%), leading to a mean number of 3.7 +/- 2.3
      infections per child: HRV-A in 72 cases (22.1%), HRV-B in 29 (8.9%), HRV-C in 122
      (37.4%), and non-typeable HRV in 103 (31.6%). Shedding was significantly longer
      for HRV-A (14 days) and HRV-B (14 days) than HRV-C (7 days; p = 0.002 and p =
      0.012). Most of the HRV infections (209/326, 64.1%) remained asymptomatic and,
      when symptomatic, were of marginal clinical relevance. CONCLUSIONS: In healthy
      young children, HRV infection is extremely frequent, generally asymptomatic or
      with a mild clinical presentation, and viral shedding is limited in time.

PMID- 25866345
TI  - Deranged liver function tests in a patient with hepatitis B.

PMID- 25866346
TI  - Evaluation of DNA extraction methods for the detection of Cytomegalovirus in
      dried blood spots.
AB  - BACKGROUND: Dried blood spots (DBS) are collected universally from newborns and
      may be valuable for the diagnosis of congenital Cytomegalovirus (CMV) infection.
      The reported analytical sensitivity for DBS testing compared to urine or saliva
      varies greatly across CMV studies. The purpose of this study was to directly
      compare the performance of various DNA extraction methods for identification of
      CMV in DBS including those used most often in CMV studies. STUDY DESIGN:
      Whatman((r)) Grade 903 filter paper cards were spotted with blood samples from 25
      organ transplant recipients who had confirmed CMV viremia. Six DNA extraction
      methods were compared for relative yield of viral and cellular DNA: 2 manual
      solution-based methods (Gentra Puregene, thermal shock), 2 manual silica column
      based methods (QIAamp DNA Mini, QIAamp DNA Investigator), and 2 automated methods
      (M48 MagAttract Mini, QIAcube Investigator). DBS extractions were performed in
      triplicate followed by real-time quantitative PCR (qPCR). RESULTS: For extraction
      of both viral and cellular DNA, two methods (QIAamp DNA Investigator and thermal
      shock) consistently gave the highest yields, and two methods (M48 MagAttract Mini
      and QIAamp DNA Mini) consistently gave the lowest yields. There was an average 3
      fold difference in DNA yield between the highest and lowest yield methods.
      CONCLUSION: The choice of DNA extraction method is a major factor in the ability
      to detect low levels of CMV in DBS and can largely account for the wide range of
      DBS sensitivities reported in studies to date.

PMID- 25866347
TI  - Reactivation of herpes simplex type 1 in pneumococcal meningitis.
AB  - BACKGROUND: Acute bacterial meningitis (ABM) and herpes simplex type 1 (HSV-1)
      encephalitis are two rare but serious infections affecting the central nervous
      system (CNS). Concurrent bacterial and viral CNS infection has occasionally been
      reported. OBJECTIVES: To illustrate the possibility of intrathecal infection with
      both Streptococcus pneumonia and HSV-1 by presenting a case and to examine
      whether herpesvirus reactivation is common in ABM. STUDY DESIGN: We report a case
      diagnosed with HSV-1 reactivation in the cerebrospinal fluid (CSF) during
      treatment for pneumococcal ABM. A retrospective analysis of CSF samples from 21
      patients with ABM was performed, with analysis of DNA from HSV-1 and four other
      neurotropic herpesviruses. RESULTS: All 21CSF samples were negative for HSV-1,
      HSV-2, varicella zoster-virus, Epstein-Barr virus and human herpesvirus 6 DNA by
      PCR. CONCLUSIONS: Although herpesvirus infection does not seem to be a common
      phenomenon in ABM we suggest that HSV-1 reactivation could be kept in mind if
      patients with ABM show symptoms or signs compatible with encephalitis.

PMID- 25866348
TI  - Toxic megacolon and human Cytomegalovirus in a series of severe ulcerative
      colitis patients.
AB  - BACKGROUND: Human Cytomegalovirus (HCMV) infection has been reported to be a
      cause of refractory ulcerative colitis (UC). Toxic megacolon (TM) is a rare but
      severe complication of an acute attack of UC. OBJECTIVES: Aim of this study is to
      evaluate in a case-control study the association between HCMV and TM. STUDY
      DESIGN: All patients who were admitted at Medicine Department of V. Cervello
      Hospital in Palermo (tertiary referral center) for a severe UC flare-up
      complicated by the onset of TM (diameter of the transverse colon>6 cm) between
      January 1990 and November 2011 were identified through the electronic database. A
      total of 24 consecutive patients (16 male/8 female) with TM were identified. Each
      case of TM were individually matched by sex, age, extent of the underlying
      disease to 24 severe UC controls who did not develop TM. A further non matched
      control population of 48 severe UC was included. Haematoxilin and eosin stain,
      immunohistochemical procedure and nested polymerase chain reaction were performed
      to detect HCMV genes and proteins on rectal biopsies or surgical specimens. Pp65
      antigenemia was performed in order to diagnose any possible systemic infection.
      HCMV frequency was compared between patients with and without TM during follow
      up, using Fisher's Exact test. RESULTS AND CONCLUSIONS: HCMV was detected in
      histological specimens of 11 patients (46%) with TM compared to 2 (9%) severe UC
      matched controls (P = 0.0078) and 7 (14%) unmatched controls (p = 0,003). In
      severe colitis the presence of HCMV is more frequently associated with TM.

PMID- 25866349
TI  - A rapid and specific real time RT-PCR assay for diagnosis of Toscana virus
      infection.
AB  - BACKGROUND: To scan a virus (TOSV) belongs to the Phlebovirus genus within the
      Bunyaviridae family. TOSV is an arbovirus transmitted by sandflies. In
      Mediterranean countries, TOSV is one of the major viral pathogens involved in
      aseptic meningitis and meningoencephalitis. OBJECTIVES: Development and
      assessment of a new sensitive and specific real-time RT-PCR assay for TOSV
      diagnosis. STUDY DESIGN: TOSV-specific primers and probe targeting the S-segment
      of the genome were designed, based on recent TOSV sequences available in public
      databases. Sensitivity was assessed using 10-fold serial dilutions of a RNA
      transcript and serial dilutions of TOSV strains isolated from infected human
      beings. Specificity was determined by testing RNA extracts from closely related
      Phleboviruses. The assay was then used for TOSV infection diagnosis in 971
      clinical samples and for TOSV detection in 2000 sandflies. RESULTS: The real-time
      RT-PCR assay exhibited a sensitivity of under 257 copies per reaction for the RNA
      transcripts and 0.0056 and 0.014 TCID50 of Italian and Spanish TOSV genotypes per
      reaction, respectively. No other close Phleboviruses were detected. TOSV was
      identified in 17 clinical samples and in 3 sandflies. CONCLUSIONS: The assay
      described is a rapid, robust and reliable real-time RT-PCR test for accurate
      diagnosis of human TOSV infection as well as for the surveillance of TOSV in
      vector populations.

PMID- 25866350
TI  - Cost-effectiveness of breast cancer screening policies using simulation.
AB  - In this paper, we study breast cancer screening policies using computer
      simulation. We developed a multi-state Markov model for breast cancer
      progression, considering both the screening and treatment stages of breast
      cancer. The parameters of our model were estimated through data from the Canadian
      National Breast Cancer Screening Study as well as data in the relevant
      literature. Using computer simulation, we evaluated various screening policies to
      study the impact of mammography screening for age-based subpopulations in Canada.
      We also performed sensitivity analysis to examine the impact of certain
      parameters on number of deaths and total costs. The analysis comparing screening
      policies reveals that a policy in which women belonging to the 40-49 age group
      are not screened, whereas those belonging to the 50-59 and 60-69 age groups are
      screened once every 5 years, outperforms others with respect to cost per life
      saved. Our analysis also indicates that increasing the screening frequencies for
      the 50-59 and 60-69 age groups decrease mortality, and that the average number of
      deaths generally decreases with an increase in screening frequency. We found that
      screening annually for all age groups is associated with the highest costs per
      life saved. Our analysis thus reveals that cost per life saved increases with an
      increase in screening frequency. 

PMID- 25866351
TI  - Impact of contra-lateral breast reshaping on mammographic surveillance in women
      undergoing breast reconstruction following mastectomy for breast cancer.
AB  - BACKGROUND: The ultimate goal of breast reconstruction is to achieve symmetry
      with the contra-lateral breast. Contra-lateral procedures with wide parenchymal
      rearrangements are suspected to impair mammographic surveillance. This study aims
      to evaluate the impact on mammographic detection of mastopexies and breast
      reductions for contralateral adjustment in breast reconstruction. PATIENTS AND
      METHODS: We retrospectively evaluated 105 women affected by uni-lateral breast
      cancer who underwent mastectomy and immediate two-stage reconstruction between
      2002 and 2007. We considered three groups according to the contra-lateral
      reshaping technique: mastopexy or breast reduction with inferior dermoglandular
      flap (group 1); mastopexy or breast reduction without inferior dermoglandular
      flap (group 2); no contra-lateral reshaping (group 3). We assessed qualitative
      mammographic variations and breast density in the three groups. RESULTS:
      Statistically significant differences have been found when comparing reshaped
      groups with non reshaped groups regarding parenchymal distortions, skin
      thickening and stromal edema, but these differences did not affect cancer
      surveillance. The surveillance mammography diagnostic accuracy in contra-lateral
      cancer detection was not significantly different between the three groups (p =
      0.56), such as the need for MRI for equivocal findings at mammographic contra
      lateral breast (p = 0.77) and the need for core-biopsies to confirm mammographic
      suspect of contra-lateral breast cancer (p = 0.90). CONCLUSIONS: This study
      confirms previous reports regarding the safety of mastopexies and breast
      reductions when performed in the setting of contra-lateral breast reshaping after
      breast reconstruction. Mammographic accuracy, sensitivity and specificity are not
      affected by the glandular re-arrangement. These results provide a further
      validation of the safety of current reconstructive paradigms.

PMID- 25866352
TI  - A novel maternally inherited 8q24.3 and a rare paternally inherited 14q23.3 CNVs
      in a family with neurodevelopmental disorders.
AB  - A 7-year-old female with developmental delay (DD), autism spectrum disorder
      (ASD), intellectual disability (ID), attention deficit hyperactivity disorder
      (ADHD), and seizures was referred to our laboratory for oligomicroarray analysis.
      The analysis revealed a 540 kb microdeletion in the chromosome 8q24.3 region
      (143,610,058-144,150,241) encompassing multiple genes. Two siblings of the
      proband were also analyzed. The proband's older sister with DD, seizures, and ASD
      has a 438 kb intragenic microdeletion of the GPHN gene in the chromosome 14q23.3
      region (67,105,512-67,543,291) containing multiple exons, while the proband's
      older brother with DD, ASD, ID, and ADHD has both the 8q24.3 and the 14q23.3
      deletions. All three siblings have a normal karyotype at the 650 G-band level of
      resolution. Parental FISH analysis indicates that the mother is a carrier for the
      8q24.3 deletion and the father is a carrier for the 14q23.3 deletion. The 8q24.3
      deletion seen in our patients has not been reported in the literature, while the
      small deletions of the 14q23.3 region involving multiple exons of the GPHN gene
      have been reported in a handful of patients in a recent study. The size of the
      8q24.3 deletion and its genomic content, as well as the maternal family history,
      strongly suggest the association between the deletion and the neurodevelopmental
      disorders. Our study also provides more evidence in support of the association
      between GPHN deletion and neurodevelopmental disorders.

PMID- 25866353
TI  - Efficient use of systems mapping without expert knowledge: Comment on "Mapping
      complex traits as a dynamic system" by L. Sun and R. Wu.

PMID- 25866354
TI  - QTL mapping - Current status and challenges: Comment on "Mapping complex traits
      as a dynamic system" by L. Sun and R. Wu.

PMID- 25866356
TI  - International caesarean section rates: the rising tide.

PMID- 25866355
TI  - Use of the Robson classification to assess caesarean section trends in 21
      countries: a secondary analysis of two WHO multicountry surveys.
AB  - BACKGROUND: Rates of caesarean section surgery are rising worldwide, but the
      determinants of this increase, especially in low-income and middle-income
      countries, are controversial. In this study, we aimed to analyse the contribution
      of specific obstetric populations to changes in caesarean section rates, by using
      the Robson classification in two WHO multicountry surveys of deliveries in health
      care facilities. The Robson system classifies all deliveries into one of ten
      groups on the basis of five parameters: obstetric history, onset of labour, fetal
      lie, number of neonates, and gestational age. METHODS: We studied deliveries in
      287 facilities in 21 countries that were included in both the WHO Global Survey
      of Maternal and Perinatal Health (WHOGS; 2004-08) and the WHO Multi-Country
      Survey of Maternal and Newborn Health (WHOMCS; 2010-11). We used the data from
      these surveys to establish the average annual percentage change (AAPC) in
      caesarean section rates per country. Countries were stratified according to Human
      Development Index (HDI) group (very high/high, medium, or low) and the Robson
      criteria were applied to both datasets. We report the relative size of each
      Robson group, the caesarean section rate in each Robson group, and the absolute
      and relative contributions made by each to the overall caesarean section rate.
      FINDINGS: The caesarean section rate increased overall between the two surveys
      (from 26.4% in the WHOGS to 31.2% in the WHOMCS, p=0.003) and in all countries
      except Japan. Use of obstetric interventions (induction, prelabour caesarean
      section, and overall caesarean section) increased over time. Caesarean section
      rates increased across most Robson groups in all HDI categories. Use of induction
      and prelabour caesarean section increased in very high/high and low HDI
      countries, and the caesarean section rate after induction in multiparous women
      increased significantly across all HDI groups. The proportion of women who had
      previously had a caesarean section increased in moderate and low HDI countries,
      as did the caesarean section rate in these women. INTERPRETATION: Use of the
      Robson criteria allows standardised comparisons of data across countries and
      timepoints and identifies the subpopulations driving changes in caesarean section
      rates. Women who have previously had a caesarean section are an increasingly
      important determinant of overall caesarean section rates in countries with a
      moderate or low HDI. Strategies to reduce the frequency of the procedure should
      include avoidance of medically unnecessary primary caesarean section. Improved
      case selection for induction and prelabour caesarean section could also reduce
      caesarean section rates. FUNDING: None.

PMID- 25866357
TI  - National trends in incidence and outcomes in lower extremity amputations in
      people with and without diabetes in Spain, 2001-2012.
AB  - AIMS: To describe trends in the incidence and outcomes of lower-extremity
      amputations (LEAs) in patients with T1DM and T2DM in Spain, 2001-2012. METHODS:
      We used national hospital discharge data. Incidence of discharges attributed to
      LEA procedures were calculated stratified by diabetes status and type of LEA.
      Joinpoint log-linear regression for incidence trends and logistic regression for
      factors associated with in-hospital mortality were used. RESULTS: From 2001 to
      2012, 73,302 minor LEAs and 64,710 major LEAs were performed. We found that
      incidence of minor LEA procedures in T1DM patients decreased by 9.84% per year
      from 2001 to 2008 and then remained stable through 2012. In T2DM patients, LEA
      increased by 1.89% per year over the entire study period. Among patients with
      T1DM, major LEA incidence rate decreased by 10.5% from 2001 to 2012. In patients
      with T2DM, it increased by 4.29% from 2001 to 2004, and then decreased by 1.85%
      through 2012. In-hospital mortality after major or minor LEAs was associated with
      older age in all groups and with being female in T2DM and in people without
      diabetes. CONCLUSIONS: Our national data show a decrease in the incidence of
      minor LEAs in patients with diabetes and in major LEAS in patients with T1DM over
      the period of study. In patients with T2DM, we found a decrease between 2004 and
      2012. An additional improvement in preventive care, such as the introduction of
      diabetes foot units in hospitals, is necessary.

PMID- 25866358
TI  - Peer-assisted teaching: An interventional study.
AB  - Peer-assisted learning (PAL) as an educational philosophy benefits both the peer
      teacher and peer-learner. The changing role of paramedicine towards autonomous
      and professional practice demands future paramedics to be effective educators.
      Yet PAL is not formally integrated in undergraduate paramedic programs. We aimed
      to examine the effects of an educational intervention on students' PAL
      experiences as peer-teachers. Two one-hour workshops were provided prior to PAL
      teaching sessions including small group activities, individual reflections, role
      plays and material notes. Peer-teachers completed the Teaching Style Survey,
      which uses a five-point Likert scale to measure participants' perceptions and
      confidence before and after PAL involvement. Thirty-eight students were involved
      in an average of 3.7 PAL sessions. The cohort was predominated by males (68.4%)
      aged <= 25 (73.7%). Following PAL, students reported feeling more confident in
      facilitating tutorial groups (p = 0.02). After the PAL project peer-teachers were
      also more likely to set high standards for their learners (p = 0.009). This PAL
      project yielded important information for the continual development of paramedic
      education. Although PAL increases students' confidence, the full role of PAL in
      education remains unexplored. The role of the university in this must also be
      clearly clarified. 

PMID- 25866359
TI  - Using an evidence-based care bundle to improve Thai emergency nurses' knowledge
      of care for patients with severe traumatic brain injury.
AB  - There is known variation in Thai nurses' knowledge regarding the best available
      evidence for care of patients with severe traumatic brain injury. The purpose of
      this study was to examine the impact of an evidence-based care bundle on Thai
      emergency nurses' knowledge regarding management of patients with severe
      traumatic brain injury. A pre-test/post-test design was used. The study
      intervention was an evidence-based care bundle for initial nursing management of
      patients with severe traumatic brain injury. Data were collected from 31
      Registered Nurses using multiple choice questions. Results revealed a
      statistically significant improvement in overall knowledge scores after care
      bundle implementation (p < 0.001). There were statistically significant
      improvements in five areas of knowledge: understanding of target end-tidal carbon
      dioxide levels (p < 0.001), implications of hypocapnia in severe traumatic brain
      injury (p = 0.01), implications of hypercapnia in severe traumatic brain injury
      (p = 0.02), importance of maintaining head and neck in neutral position (p =
      0.05), and administration of sedatives and analgesics in severe traumatic brain
      injury (p = 0.01). This study suggested that implementation of an evidence-based
      care bundle improved emergency nurses' knowledge regarding management of patients
      with severe traumatic brain injury. 

PMID- 25866360
TI  - Spatial and temporal control of cell aggregation efficiently directs human
      pluripotent stem cells towards neural commitment.
AB  - 3D suspension culture is generally considered a promising method to achieve
      efficient expansion and controlled differentiation of human pluripotent stem
      cells (hPSCs). In this work, we focused on developing an integrated culture
      platform for expansion and neural commitment of hPSCs into neural precursors
      using 3D suspension conditions and chemically-defined culture media. We evaluated
      different inoculation methodologies for hPSC expansion as 3D aggregates and
      characterized the resulting cultures in terms of aggregate size distribution. It
      was demonstrated that upon single-cell inoculation, after four days of culture,
      3D aggregates were composed of homogenous populations of hPSC and were
      characterized by an average diameter of 139 +/- 26 MUm, which was determined to
      be the optimal size to initiate neural commitment. Temporal analysis revealed
      that upon neural specification it is possible to maximize the percentage of
      neural precursor cells expressing the neural markers Sox1 and Pax6 after nine
      days of culture. These results highlight our ability to define a robust method
      for production of hPSC-derived neural precursors that minimizes processing steps
      and that constitutes a promising alternative to the traditional planar adherent
      culture system due to a high potential for scaling-up. 

PMID- 25866361
TI  - Survival of a child with spinal muscular atrophy and acute respiratory distress
      syndrome.
AB  - Spinal muscular atrophy (SMA), a lower motor neuron anterior horn cell disease,
      causes significant respiratory morbidity and mortality in children. Acute
      respiratory distress syndrome (ARDS) accounts for 1-4% of all Pediatric Intensive
      Care Unit (PICU) admissions. Management outcomes for ARDS in patients with SMA
      have not been described. We present the case of a 5-year-old boy with Type II SMA
      and ARDS requiring invasive mechanical ventilation. He improved with meticulous
      management of mechanical ventilation, airway clearance, fluid/nutrition, and
      sedation/analgesia. He was successfully extubated after 14 days of invasive
      mechanical ventilation and discharged home after a 20 day hospitalization.

PMID- 25866362
TI  - Pculin02H, a curcumin derivative, inhibits proliferation and clinical drug
      resistance of HER2-overexpressing cancer cells.
AB  - Amplification of the HER2 gene (also known as neu or ErbB2) or overexpression of
      HER2 protein has become a solicitous therapeutic target in metastatic and
      clinical drug-resistance cancer. In our present work, a new series of curcumin
      derivatives were designed and synthesized using curcumin as model. Here, we
      evaluated whether curcumin derivatives have better efficiency to degrade HER2
      than curcumin. Among these test compounds, pculin02H had better efficiency to
      inhibit the expression of HER2 than curcumin. Moreover, pculin02H preferentially
      suppressed the growth of HER2-overexpressing cancer cell lines. Pculin02H induced
      G2/M cell cycle arrest followed by apoptosis. Interestingly, our results
      suggested that a posttranslational mechanism contributed to pculin02H-induced
      HER2 depletion in HER2-overexpressing cancer cells. We found that pculin02H
      significantly enhanced the antitumor efficacy of clinical drugs on HER2
      overexpressing cancer cells as well as efficiently reduced HER2-induced drug
      resistance. These findings may provide an alternative preventive or therapeutic
      strategy against HER2-overexpressing cancer cells. 

PMID- 25866363
TI  - Naringenin suppresses TPA-induced tumor invasion by suppressing multiple signal
      transduction pathways in human hepatocellular carcinoma cells.
AB  - Naringenin, a common dietary flavonoid abundantly present in fruits and
      vegetables, is believed to possess strong anti-proliferative properties and the
      ability to induce apoptosis in hepatoma cell lines. However, there are no reports
      describing its effects on the invasion and metastasis of hepatoma cell lines, and
      the detailed molecular mechanisms of its effects are still unclear. In this
      study, we investigated the mechanisms underlying naringenin-mediated inhibition
      of 12-O-Tetradecanoylphorbol-13-acetate (TPA)-induced cell invasion and
      inhibition of secreted and cytosolic MMP-9 production in human hepatoma cells
      (HepG2, Huh-7, and HA22T) and murine embryonic liver cells (BNL CL2). Naringenin
      suppressed MMP-9 transcription by inhibiting activator protein (AP)-1 and nuclear
      factor-kappaB (NF-kappaB) activity. It suppressed TPA-induced AP-1 activity
      through inhibiting the phosphorylation of the extracellular signal-related kinase
      (ERK) and c-Jun N-terminal kinase (JNK) signaling pathways, and it suppressed TPA
      induced inhibition of NF-kappaB nuclear translocation through IkappaB.
      Additionally, it suppressed TPA-induced activation of ERK/phosphatidylinositol 3
      kinase/Akt upstream of NF-kappaB and AP-1. These data suggest that naringenin
      suppresses the invasiveness and metastatic potential of hepatocellular carcinoma
      (HCC) by inhibiting multiple signal transduction pathways. 

PMID- 25866364
TI  - Evolution of petaloidy in the zingiberales: An assessment of the relationship
      between ultrastructure and gene expression patterns.
AB  - BACKGROUND: The development of petal-like organs has occurred repetitively
      throughout angiosperm evolution. Despite homoplasy, it is possible that common
      underlying molecular mechanisms are repeatedly recruited to drive the development
      of petaloid organs. In Zingiberales, infertile, petal-like structures replace
      fertile stamens, resulting in petaloidy in androecial whorls. Assuming that
      androecial petaloidy is a shared derived characteristic, we expect to find common
      ultrastructure and molecular mechanisms underlying androecial petaloidy across
      Zingiberales. RESULTS: We show that petaloidy in Zingiberales is associated with
      tightly packed, protruding epidermal cells. Expression patterns for candidate
      genes involved in petal identity differ between the petaloid organs of Costaceae
      v. Cannaceae, despite similar macro- and microscopic organization. For all
      candidate gene families analyzed, our data suggest at least one Zingiberales
      specific duplication event. CONCLUSIONS: Our data suggest that the patterns of B
      class gene expression across the Zingiberales do not correlate with the
      occurrence of petaloidy, indicating that androecial petaloidy might have evolved
      independently of B-class gene expression in some lineages. It is possible that
      gene duplication may play a role in the diversity of petaloid structures found
      throughout the Zingiberales. It is likely that Zingiberales petaloidy may also
      result from the deployment of genes other than those involved in specification of
      petal identity. Developmental Dynamics 244:1121-1132, 2015. (c) 2015 Wiley
      Periodicals, Inc.

PMID- 25866366
TI  - Acute exercise does not decrease liver fat in men with overweight or NAFLD.
AB  - Elevated hepatic lipid content (IntraHepatic Lipid, IHL) increases the risk of
      metabolic complications. Although prolonged exercise training lowers IHL, it is
      unknown if acute exercise has the same effect. Furthermore, hepatic ATP content
      may be related to insulin resistance and IHL. We aimed to investigate if acute
      exercise leads to changes in IHL and whether this is accompanied by changes in
      hepatic ATP. Twenty-one men (age 54.8 +/- 7.2 years, BMI 29.7 +/- 2.2 kg/m(2))
      performed a 2 h cycling protocol, once while staying fasted and once while
      ingesting glucose. IHL was determined at baseline, 30 min post-exercise and 4 h
      post-exercise. Additionally ATP/Total P ratio was measured at baseline and 4 h
      post-exercise. Compared with baseline values we did not observe any statistically
      significant changes in IHL within 30 min post-exercise in neither the fasted nor
      the glucose-supplemented condition. However, IHL was elevated 4 h post-exercise
      compared with baseline in the fasted condition (from 8.3 +/- 1.8 to 8.7 +/- 1.8%,
      p = 0.010), an effect that was blunted by glucose supplementation (from 8.3 +/-
      1.9 to 8.3 +/- 1.9%, p = 0.789). Acute exercise does not decrease liver fat in
      overweight middle-aged men. Moreover, IHL increased 4 h post-exercise in the
      fasted condition, an increase that was absent in the glucose-supplemented
      condition. These data suggest that a single bout of exercise may not be able to
      lower IHL. 

PMID- 25866367
TI  - Coordinated action of Axin1 and Axin2 suppresses beta-catenin to regulate muscle
      stem cell function.
AB  - The resident stem cells of skeletal muscle are satellite cells, which are
      regulated by both canonical and non-canonical Wnt pathways. Canonical Wnt
      signalling promotes differentiation, and is controlled at many levels, including
      via Axin1 and Axin2-mediated beta-catenin degradation. Axin1 and Axin2 are
      thought equivalent suppressors of canonical Wnt signalling, although Axin2 is
      also a Wnt target gene. We show that Axin1 expression was higher in proliferating
      satellite cells, while Axin2 was up-regulated during differentiation. siRNA
      mediated Axin1 knockdown changed cell morphology, suppressed proliferation and
      promoted myogenic differentiation. Simultaneous knockdown of both Axin1 and beta
      catenin rescued proliferation and partially, premature differentiation.
      Surprisingly, retroviral-mediated overexpression of Axin2 was unable to
      compensate for knockdown of Axin1 in satellite cells, indicating that Axin1 and
      Axin2 are not fully redundant. Isolated satellite cells from Axin2-null mice also
      had no major phenotype. However, siRNA-mediated knockdown of Axin1 in Axin2-null
      cells strongly inhibited proliferation, while inducing differentiation, clear
      nuclear localisation of beta-catenin, up-regulation of canonical Wnt target genes
      (Axin2, Lef1, Tcf4, Pitx2c and Lgr5) and activation of a TCF reporter construct.
      Again, concomitant knockdown of Axin1 and beta-catenin in Axin2-null satellite
      cells rescued morphology and proliferation, but only partially prevented
      precocious differentiation. Thus, Axin1 and Axin2 do not have equivalent
      functions in satellite cells, but are both involved in repression of Wnt/beta
      catenin signalling to maintain proliferation and contribute to controlling timely
      myogenic differentiation. 

PMID- 25866369
TI  - Self-assembly of active attractive spheres.
AB  - We study the self-assembly of a system of self-propelled, Lennard-Jones particles
      using Brownian dynamics simulations. We examine the state diagrams of the system
      for different rotational diffusion coefficients of the self-propelled motion of
      the particles. For fast rotational diffusion, the state diagram exhibits a strong
      similarity to that of the equilibrium Lennard-Jones fluid. As we decrease the
      rotational diffusion coefficient, the state diagram is slowly transformed.
      Specifically, the liquid-gas coexistence region is gradually replaced by a highly
      dynamic percolating network state. We find significant local alignment of the
      particles in the percolating network state despite the absence of aligning
      interactions, and propose a simple mechanism to justify the formation of this
      novel state. 

PMID- 25866368
TI  - Heterodimerization of human orexin receptor 1 and kappa opioid receptor promotes
      protein kinase A/cAMP-response element binding protein signaling via a Galphas
      mediated mechanism.
AB  - Orexin and dynorphin are co-expressed in the same synaptic vesicles of
      hypothalamic neurons and play opposing roles in cocaine self-administration,
      brain stimulation reward, and impulsivity in ventral tegmental area (VTA), where
      dopamine neurons express both OX1R and KORs. However, detailed mechanisms of how
      the coreleased peptides and both receptors fine-tune their signalings and
      physiological/behavioral effects together remain unclear. Here we explore the
      possibility of heterodimerization between OX1R and KOR and reveal novel signal
      transduction mechanisms. First, we demonstrated co-expression of OX1R and KOR in
      rat hippocampal neurons by single-cell PCR. Furthermore, heterodimerization
      between OX1R and KOR was examined using bioluminescence and fluorescence
      resonance energy transfer (BRET and FRET). Our data revealed that human OX1R and
      KOR heterodimerize, and this heterodimer associates with Galphas, leading to
      increased protein kinase A (PKA) signaling pathway activity, including
      upregulation of intracellular cAMP levels and cAMP-response element (CRE)
      luciferase reporter activity, resulting in increased cAMP-response element
      binding protein (CREB) phosphorylation. These results support the view that OX1R
      and KOR heterodimerization might have an anti-depressive role. 

PMID- 25866370
TI  - Quantitative analysis of 17 amino acids in tobacco leaves using an amino acid
      analyzer and chemometric resolution.
AB  - A method was developed for quantifying 17 amino acids in tobacco leaves by using
      an A300 amino acid analyzer and chemometric resolution. In the method, amino
      acids were eluted by the buffer solution on an ion-exchange column. After
      reacting with ninhydrin, the derivatives of amino acids were detected by
      ultraviolet detection. Most amino acids are separated by the elution program.
      However, five peaks of the derivatives are still overlapping. A non-negative
      immune algorithm was employed to extract the profiles of the derivatives from the
      overlapping signals, and then peak areas were adopted for quantitative analysis
      of the amino acids. The method was validated by the determination of amino acids
      in tobacco leaves. The relative standard deviations (n = 5) are all less than
      2.54% and the recoveries of the spiked samples are in a range of 94.62-108.21%.
      The feasibility of the method was proved by analyzing the 17 amino acids in 30
      tobacco leaf samples. 

PMID- 25866371
TI  - [Neurocognitive outcome in childhood brain tumor survivors].
AB  - Advances in treatment have significantly improved the survival rate of children
      with brain tumour. This review describes risk factors of late neurocognitive
      effect, the different type of neurocognitive side effect according to the type of
      tumour and the rehabilitation. The best knowledge of cognitive sequelae allowed
      to propose supported appropriate and specific disorders including school
      facilities for younger and adaptation of professional situation for adults.
      Furthermore, this understanding allows to link with the patient's quality of life
      and to approach the person in its specificity and overall. 

PMID- 25866372
TI  - [Nab-paclitaxel use in pancreatic cancer: practical aspects and consequences in a
      French oncology day-care unit].

PMID- 25866373
TI  - Family practitioners screening for HIV infection.
AB  - BACKGROUND: We assessed how family physicians screened for HIV infection in
      Paris, in 2013 and whether their practice had changed after publication of the
      HAS (French National Authority for Health) recommendation for systematic
      screening. METHOD: Family practitioners (FPs) in Paris answered a questionnaire
      by e-mail or regular mail from January to April 2013. The statistical analysis
      was performed with the Chi(2) test. RESULTS: Four hundred and seven FPs answered
      (77.8% response rate). FPs did not always identify risk cases: 78% in case of
      sexually transmitted infection, but 32% for partner change, 39% for patients from
      a highly HIV endemic country, and 21% for sexually active teenagers or adults.
      Practices differed according to districts. FPs in the 1st and in the Northeastern
      Paris districts detected risk cases for HIV more often than their colleagues, and
      they used screening more often, with, consequently, more frequently positive
      results. The screening strategies also differed according to the FPs' demographic
      characteristics and their type of practice: young (P = 0.0002) female (P = 0.02)
      FPs working in "sector 1 (patients fully reimbursed)" (P = 8.10(-5)) prescribed
      more HIV blood tests. Surprisingly, only 45% of FPs was aware of the recent
      recommendation for systematic screening of HIV. CONCLUSION: The Paris FP
      screening practices differ according to demographic characteristics, place, and
      type of practice. Screening practices have not changed since the publication of
      the new screening strategy.

PMID- 25866365
TI  - Modeling a model: Mouse genetics, 22q11.2 Deletion Syndrome, and disorders of
      cortical circuit development.
AB  - Understanding the developmental etiology of autistic spectrum disorders,
      attention deficit/hyperactivity disorder and schizophrenia remains a major
      challenge for establishing new diagnostic and therapeutic approaches to these
      common, difficult-to-treat diseases that compromise neural circuits in the
      cerebral cortex. One aspect of this challenge is the breadth and overlap of ASD,
      ADHD, and SCZ deficits; another is the complexity of mutations associated with
      each, and a third is the difficulty of analyzing disrupted development in at-risk
      or affected human fetuses. The identification of distinct genetic syndromes that
      include behavioral deficits similar to those in ASD, ADHC and SCZ provides a
      critical starting point for meeting this challenge. We summarize clinical and
      behavioral impairments in children and adults with one such genetic syndrome, the
      22q11.2 Deletion Syndrome, routinely called 22q11DS, caused by micro-deletions of
      between 1.5 and 3.0 MB on human chromosome 22. Among many syndromic features,
      including cardiovascular and craniofacial anomalies, 22q11DS patients have a high
      incidence of brain structural, functional, and behavioral deficits that reflect
      cerebral cortical dysfunction and fall within the spectrum that defines ASD,
      ADHD, and SCZ. We show that developmental pathogenesis underlying this apparent
      genetic "model" syndrome in patients can be defined and analyzed mechanistically
      using genomically accurate mouse models of the deletion that causes 22q11DS. We
      conclude that "modeling a model", in this case 22q11DS as a model for idiopathic
      ASD, ADHD and SCZ, as well as other behavioral disorders like anxiety frequently
      seen in 22q11DS patients, in genetically engineered mice provides a foundation
      for understanding the causes and improving diagnosis and therapy for these
      disorders of cortical circuit development.

PMID- 25866374
TI  - Changing profile and increasing antimicrobial resistance of uropathogenic
      bacteria in Madagascar.
AB  - OBJECTIVES: We wanted to update the distribution of community-acquired
      uropathogens and to estimate their susceptibility profile to newly available
      antibiotics in Antananarivo (Madagascar). MATERIALS AND METHODS: We conducted a 3
      year preliminary study (2011-2013) on bacteria isolated from the urine of
      patients at the Laboratory of Training and Research in Medical Biology
      (Antananarivo). RESULTS: Three hundred and fifty-seven pathogens were isolated:
      234 (65.55%) Gram-negative bacilli and 123 (34.45%) Gram-positive cocci. The most
      commonly isolated bacteria were Escherichia coli (89 strains) followed by
      Staphylococcus aureus (48 strains). Thirty-three percent of Gram-negative bacilli
      were resistant to 3 CG. Forty percent of Klebsiella pneumoniae strains were
      significantly resistant to imipenem (P = 0.01). CONCLUSIONS: The increased
      resistance to newly available antibiotics and the increased rate of Gram-positive
      cocci strains require a drastic surveillance of antibiotic resistance to ensure
      appropriate empirical treatment.

PMID- 25866375
TI  - Resveratrol-induced mitochondrial synthesis and autophagy in oocytes derived from
      early antral follicles of aged cows.
AB  - Mitochondrial numbers increase during oocyte growth. In this study, we collected
      oocytes and granulosa cell complexes (OGCs) from early antral follicles (EAFs) of
      aged cows (> 120 months of age) and examined the effects of resveratrol on
      mitochondrial generation, degradation, and quality in oocytes grown in vitro. We
      also examined the effects of resveratrol on gene expression of the granulosa
      cells. Resveratrol (20 uM) enhanced the expression of SIRT1 and induced autophagy
      in both granulosa cells and oocytes derived from aged cows. Culturing the OGCs
      with resveratrol increased mitochondrial DNA copy numbers in oocytes grown in
      vitro. Furthermore, resveratrol increased the ATP content in oocytes and improved
      the developmental ability of the oocytes to the blastocyst stage. Gene expression
      profiles in granulosa cells, as evaluated by next-generation sequencing
      technology, revealed that resveratrol enhanced the expression of EIF2-related
      genes but downregulated the expression of mammalian target of rapamycin (mTOR)-,
      inflammation-, and cholesterol homeostasis-related genes in granulosa cells. In
      conclusion, resveratrol affected both oocytes and granulosa cells derived from
      aged cows and improved the quality of oocytes grown in vitro through upregulation
      of mitochondrial biogenesis and degradation in growing oocytes and conditioning
      of granulosa cells. 

PMID- 25866376
TI  - Genotyping and interpretation of STR-DNA: Low-template, mixtures and database
      matches-Twenty years of research and development.
AB  - The introduction of Short Tandem Repeat (STR) DNA was a revolution within a
      revolution that transformed forensic DNA profiling into a tool that could be
      used, for the first time, to create National DNA databases. This transformation
      would not have been possible without the concurrent development of fluorescent
      automated sequencers, combined with the ability to multiplex several loci
      together. Use of the polymerase chain reaction (PCR) increased the sensitivity of
      the method to enable the analysis of a handful of cells. The first multiplexes
      were simple: 'the quad', introduced by the defunct UK Forensic Science Service
      (FSS) in 1994, rapidly followed by a more discriminating 'six-plex' (Second
      Generation Multiplex) in 1995 that was used to create the world's first national
      DNA database. The success of the database rapidly outgrew the functionality of
      the original system - by the year 2000 a new multiplex of ten-loci was introduced
      to reduce the chance of adventitious matches. The technology was adopted world
      wide, albeit with different loci. The political requirement to introduce pan
      European databases encouraged standardisation - the development of European
      Standard Set (ESS) of markers comprising twelve-loci is the latest iteration.
      Although development has been impressive, the methods used to interpret evidence
      have lagged behind. For example, the theory to interpret complex DNA profiles
      (low-level mixtures), had been developed fifteen years ago, but only in the past
      year or so, are the concepts starting to be widely adopted. A plethora of
      different models (some commercial and others non-commercial) have appeared. This
      has led to a confusing 'debate' about the 'best' to use. The different models
      available are described along with their advantages and disadvantages. A section
      discusses the development of national DNA databases, along with details of an
      associated controversy to estimate the strength of evidence of matches. Current
      methodology is limited to searches of complete profiles - another example where
      the interpretation of matches has not kept pace with development of theory. STRs
      have also transformed the area of Disaster Victim Identification (DVI) which
      frequently requires kinship analysis. However, genotyping efficiency is
      complicated by complex, degraded DNA profiles. Finally, there is now a detailed
      understanding of the causes of stochastic effects that cause DNA profiles to
      exhibit the phenomena of drop-out and drop-in, along with artefacts such as
      stutters. The phenomena discussed include: heterozygote balance; stutter;
      degradation; the effect of decreasing quantities of DNA; the dilution effect. 

PMID- 25866378
TI  - 40 Years of archaeal virology: Expanding viral diversity.
AB  - The first archaeal virus was isolated over 40 years ago prior to the recognition
      of the three domain structure of life. In the ensuing years, our knowledge of
      Archaea and their viruses has increased, but they still remain the most
      mysterious of life's three domains. Currently, over 100 archaeal viruses have
      been discovered, but few have been described in biochemical or structural detail.
      However, those that have been characterized have revealed a new world of
      structural, biochemical and genetic diversity. Several model systems for studying
      archaeal virus-host interactions have been developed, revealing evolutionary
      linkages between viruses infecting the three domains of life, new viral lysis
      systems, and unusual features of host-virus interactions. It is likely that the
      study of archaeal viruses will continue to provide fertile ground for fundamental
      discoveries in virus diversity, structure and function.

PMID- 25866379
TI  - Weight loss in a patient with polycystic kidney disease: when liver cysts are no
      longer innocent bystanders.
AB  - OBJECTIVE AND IMPORTANCE: Autosomal dominant polycystic kidney disease (ADPKD) is
      the most frequent inherited kidney disorder, and liver involvement represents one
      of its major extra-renal manifestations. Although asymptomatic in most patients,
      polycystic liver disease (PLD) can lead to organ compression, severe disability
      and even become life-threatening, thereby warranting early recognition and
      appropriate management. CLINICAL PRESENTATION: We report the case of a 56-year
      old woman with ADPKD and severe weight loss secondary to a giant hepatic cyst
      compressing the pylorus. Partial hepatectomy was required after failure of cyst
      aspiration and sclerotherapy, and patient's condition improved rapidly.
      DISCUSSION AND CONCLUSIONS: We discuss the presentation and classification of
      compressing liver cysts, and the available therapeutic alternatives for this
      potentially severe complication of ADPKD.

PMID- 25866377
TI  - Viral membrane fusion.
AB  - Membrane fusion is an essential step when enveloped viruses enter cells. Lipid
      bilayer fusion requires catalysis to overcome a high kinetic barrier; viral
      fusion proteins are the agents that fulfill this catalytic function. Despite a
      variety of molecular architectures, these proteins facilitate fusion by
      essentially the same generic mechanism. Stimulated by a signal associated with
      arrival at the cell to be infected (e.g., receptor or co-receptor binding, proton
      binding in an endosome), they undergo a series of conformational changes. A
      hydrophobic segment (a "fusion loop" or "fusion peptide") engages the target-cell
      membrane and collapse of the bridging intermediate thus formed draws the two
      membranes (virus and cell) together. We know of three structural classes for
      viral fusion proteins. Structures for both pre- and postfusion conformations of
      illustrate the beginning and end points of a process that can be probed by single
      virion measurements of fusion kinetics. 

PMID- 25866380
TI  - [Arachnoid cysts: Embriology and pathology].
AB  - There is still great controversy surrounding the origin of the arachnoid cyst.
      The most accepted theory in the case of congenital cysts explains how they are
      formed from an anomalous development of the arachnoid membrane, which is unfolded
      allowing the accumulation of cerebrospinal fluid inside and creating a cyst. This
      theory seems to explain the origin of convexity and sylvian cistern arachnoid
      cysts, whereas those in other locations might be due to other mechanisms. In the
      anatomopathological analysis, the arachnoid cyst wall can be seen as having few
      differences from normal, although thickened due to an increase quantity of
      collagenous material. A description of the embryological development of the
      arachnoid layer and cyst formation is presented, describing the main
      anatomopathological findings. 

PMID- 25866381
TI  - [Imaging diagnosis of arachnoid cysts].
AB  - Arachnoid cysts are malformed lesions that contain a fluid similar to the
      cerebrospinal fluid, and are usually located within the arachnoidal membrane.
      They represent 1% of all intracranial lesions, and in recent years, with the
      development of radiological techniques, the clinical detectability of arachnoid
      cysts seems to have increased. Although the majority of diagnosed arachnoid cysts
      are located in the cranial cavity and especially in the Sylvian fissure, a small
      number are located at spinal level and they can occur extra- or intra-spinally.
      An analysis is carried out, detailing the various tests used for the diagnosis of
      both intracranial and spinal arachnoids cysts, analysing the indications of each
      one depending on the location of the cysts and patient age. 

PMID- 25866382
TI  - Antithrombotic drugs, patient characteristics, and gastrointestinal bleeding:
      Clinical translation and areas of research.
AB  - Gastrointestinal bleeding (GIB) is a potentially fatal and avoidable medical
      condition that poses a burden on global health care costs. Current understanding
      of the roles of platelet activation and thrombin generation/activity in vascular
      medicine has led to the development of effective antithrombotic treatments.
      However, in parallel with a sustained coronary and cerebral flow patency, the
      increasingly intensive treatment with warfarin; direct oral anticoagulant drugs
      [DOACs], and/or with aspirin +/- clopidogrel (or +/- prasugrel or +/-
      ticagrelor), has increased the burden of GIBs related to the use of
      antithrombotic agents. Compelling evidence concerning this issue is accumulating
      to indicate that: 1) the risk of GIB related to the use of antithrombotic drugs
      dramatically differs in different clinical settings; and 2) the characteristics
      of patients (e.g., severity of illness, comorbidities) in whom it is used exert a
      greater impact on the risk of GIB than the type of antithrombotic agent employed.
      The latter concept argues for the occurrence of GIB as reflecting the presence of
      patients at the highest risk for adverse outcomes. The HAS-BLED score identifies
      subjects at risk of bleeding among those untreated and those treated with
      warfarin, DOACs and/or low-dose aspirin. Its use within the frame of a severity
      score (e.g., the CHA2DS2-VASc score in patients with atrial fibrillation) helps
      balance the benefits and the risks of an antithrombotic treatment and identify
      those patients in whom the absolute gain (vascular events prevented) outweighs
      the risk of GIB. Potential implications of the latter information in settings
      other than atrial fibrillation is thoroughly discussed.

PMID- 25866383
TI  - Clinical trial management of participant recruitment, enrollment, engagement, and
      retention in the SMART study using a Marketing and Information Technology
      (MARKIT) model.
AB  - Advances in information technology and near ubiquity of the Internet have spawned
      novel modes of communication and unprecedented insights into human behavior via
      the digital footprint. Health behavior randomized controlled trials (RCTs),
      especially technology-based, can leverage these advances to improve the overall
      clinical trials management process and benefit from improvements at every stage,
      from recruitment and enrollment to engagement and retention. In this paper, we
      report the results for recruitment and retention of participants in the SMART
      study and introduce a new model for clinical trials management that is a result
      of interdisciplinary team science. The MARKIT model brings together best
      practices from information technology, marketing, and clinical research into a
      single framework to maximize efforts for recruitment, enrollment, engagement, and
      retention of participants into a RCT. These practices may have contributed to the
      study's on-time recruitment that was within budget, 86% retention at 24 months,
      and a minimum of 57% engagement with the intervention over the 2-year RCT. Use of
      technology in combination with marketing practices may enable investigators to
      reach a larger and more diverse community of participants to take part in
      technology-based clinical trials, help maximize limited resources, and lead to
      more cost-effective and efficient clinical trial management of study participants
      as modes of communication evolve among the target population of participants.

PMID- 25866384
TI  - Does cognitive behavioral therapy strengthen the effect of bariatric surgery for
      obesity? Design and methods of a randomized and controlled study.
AB  - BACKGROUND: (Extreme) obesity is a chronic harmful condition with high risk of
      medical comorbidities and negative social and emotional consequences. Bariatric
      surgery is an effective intervention for obesity, but approximately 20 to 30% of
      the patients experience adverse outcomes after surgery and there is a need for
      augmentation of current treatment strategies. This study examines the added value
      of pre-operative cognitive behavioral therapy (CBT) focused on modification of
      thoughts and behaviors in terms of eating behavior and physical exercise as well
      as preparation for surgery and postoperative life style. We hypothesize that pre
      operative CBT will result in better weight loss maintenance, reduction of
      maladaptive eating behavior and better adherence to postoperative lifestyle on
      the long term as compared to bariatric surgery alone. METHODS: One hundred and
      twenty eight patients that are on a waiting list for bariatric surgery are
      randomly assigned to the control or treatment condition. Patients in the
      treatment condition receive 10 sessions of CBT before surgery aimed at modifying
      dysfunctional eating habits and behaviors and developing more rational weight and
      body-related beliefs in order to enable long term maintenance of a healthier
      lifestyle after surgery. Weight loss, eating behavior, eating disorders,
      depression, quality of life and psychological distress are assessed before and
      after treatment, as well as 1, 3, and 5 year following surgery.

PMID- 25866385
TI  - Proteome dynamics in health and disease. Foreword.

PMID- 25866386
TI  - Melanoma Incidence in Children and Adolescents: Decreasing Trends in the United
      States.
AB  - OBJECTIVE: To assess trends in the incidence of melanoma in children and
      adolescents in the US from 2000-2010. STUDY DESIGN: Using the Surveillance,
      Epidemiology, and End Results cancer registry data, we calculated age-adjusted
      incidence rates of melanoma in children and adolescents (age <20 years) from 2000
      2010, as well as annual percent changes. We analyzed incidence trends using
      joinpoint regression models. We further stratified incidence rates and trends by
      age group, sex, race, and melanoma-specific characteristic (histology, anatomic
      site, Breslow depth, ulceration status, lymph node involvement, and presence of
      metastasis). RESULTS: We included 1185 pediatric patients (age <20 years)
      diagnosed with melanoma from 2000-2010. In patients age <20 years overall, we
      found a significant decreasing incidence (11.58% per year) from 2004-2010.
      Overall, significant decreasing incidence trends were also noted in males,
      melanoma located on the trunk, melanoma located on the upper extremities,
      superficial spreading melanoma, and melanoma with good prognostic indicators.
      When further subdividing the pediatric population by age group, these significant
      decreasing incidence trends were most notable in adolescents (age 15-19 years),
      decreasing 11.08% per year from 2003-2010. Furthermore, in 15- to 19-year-olds,
      decreasing trends were found to be significant in melanoma located on the trunk,
      superficial spreading melanoma, and melanoma with good prognostic indicators.
      CONCLUSIONS: Decreasing trends in melanoma incidence in the pediatric population
      from 2000-2010 stand in contrast to previous reports of increasing long-term
      incidence trends. Possible contributors to these decreasing trends include
      effective public health initiatives, decreased time spent outdoors, and increased
      sunscreen use.

PMID- 25866387
TI  - Maternal Depression Trajectories and Children's Behavior at Age 5 Years.
AB  - OBJECTIVE: To assess the relationship between trajectories of maternal depression
      from pregnancy to the child's age of 5 years and children's emotional and
      behavioral difficulties at age 5 years. STUDY DESIGN: Mother-child pairs (n =
      1183) from the EDEN mother-child birth cohort study based in France were followed
      from 24 to 28 weeks of pregnancy to the child's fifth birthday. Children's
      behavior at age 5 years was assessed with the Strengths and Difficulties
      Questionnaire. Maternal depression was assessed repeatedly with the Center for
      Epidemiological Studies Depression questionnaire (pregnancy, 3, and 5 years of
      age) and the Edinburgh Postnatal Depression Scale (4, 8, and 12 months
      postpartum). Homogeneous latent trajectory groups of maternal depression were
      identified within the study population and correlated with Strengths and
      Difficulties Questionnaire scores by the use of multivariate linear regression
      analyzes. RESULTS: Five trajectories of maternal symptoms of depression were
      identified: no symptoms (62.0%); persistent intermediate-level depressive
      symptoms (25.3%); persistent high depressive symptoms (4.6%); high symptoms in
      pregnancy only (3.6%); and high symptoms in the child's preschool period only
      (4.6%). Children whose mothers had persistent depressive symptoms--either
      intermediate or high--had the greatest levels of emotional and behavioral
      difficulties at age 5 years. In addition, compared with children whose mothers
      were never depressed, those whose mothers had high symptoms in the preschool
      period also had increased levels of emotional symptoms, conduct problems, and
      peer problems. CONCLUSIONS: Maternal depression symptoms are related to
      children's emotional and behavioral problems, particularly if they are persistent
      (29.9%) or occur during early childhood (4.6%).

PMID- 25866388
TI  - Spatiotemporal brassinosteroid signaling and antagonism with auxin pattern stem
      cell dynamics in Arabidopsis roots.
AB  - The spatiotemporal balance between stem cell maintenance, proliferation, and
      differentiation determines the rate of root growth and is controlled by hormones,
      including auxin and brassinosteroid (BR). However, the spatial actions of BR and
      its interactions with auxin remain unclear in roots. Here, we show that
      oppositely patterned and antagonistic actions of BR and auxin maintain the stem
      cell balance and optimal root growth. We discover a pattern of low levels of
      nuclear-localized BR-activated transcription factor BZR1 in the stem cell niche
      and high BZR1 levels in the transition-elongation zone. This BZR1 pattern
      requires local BR catabolism and auxin synthesis, as well as BR signaling. Cell
      type-specific expression of a constitutively active form of BZR1 confirms that
      the high and low levels of BZR1 are required for the normal cell behaviors in the
      elongation zone and quiescent center (QC), respectively. Comparison between BR
      responsive, BZR1-targeted, auxin-responsive, and developmental zone-specific
      transcriptomes indicates that BZR1 mostly activates its target genes expressed in
      the transition-elongation zone, but represses genes in the QC and surrounding
      stem cells, and that BR and auxin have overall opposite effects on gene
      expression. Genetic and physiological interactions support that a balance between
      the antagonistic actions of BR and auxin is required for optimal root growth.
      These results demonstrate that the level and output specificity of BR signaling
      are spatially patterned and that, in contrast to their synergism in shoots, BR
      and auxin interact antagonistically in roots to control the spatiotemporal
      balance of stem cell dynamics required for optimal root growth.

PMID- 25866389
TI  - Rewiring of cellular division site selection in evolution of fission yeasts.
AB  - Strategies to position the division apparatus exhibit a bewildering diversity
      [1], but how these mechanisms evolve remains virtually unknown. Here, we explore
      the plasticity of division site positioning in fission yeasts Schizosaccharomyces
      pombe and Schizosaccharomyces japonicus. We demonstrate that, whereas both
      species divide in the middle, only S. pombe uses the anillin Mid1 as a primary
      nucleus-derived cue to assemble the actomyosin ring at the equatorial cortex. We
      trace this variance to the divergence in subcellular targeting of Mid1 and show
      that duplication of an ancestral anillin early in the Schizosaccharomyces lineage
      may have led to subfunctionalization of the Mid1 orthologs. In contrast to S.
      pombe, medial assembly of the actomyosin ring in mitotic S. japonicus relies on
      the cortical anchor protein Cdc15 regulated by the tip-localized kinase Pom1. Our
      data suggest that division site placement is determined by cortical positioning
      of the actomyosin-plasma membrane linkers and that both identity of the linker
      and control of its subcellular targeting are highly modular.

PMID- 25866390
TI  - Wood Formation in Trees Is Increased by Manipulating PXY-Regulated Cell Division.
AB  - The woody tissue of trees is composed of xylem cells that arise from divisions of
      stem cells within the cambial meristem. The rate of xylem cell formation is
      dependent upon the rate of cell division within the cambium and is controlled by
      both genetic and environmental factors. In the annual plant Arabidopsis,
      signaling between a peptide ligand CLE41 and a receptor kinase PXY controls
      cambial cell divisions; however, the pathway regulating secondary growth in trees
      has not been identified. Here, we show that an aspen receptor kinase PttPXY and
      its peptide ligand PttCLE41 are functional orthologs and act to control a
      multifunctional pathway that regulates both the rate of cambial cell division and
      woody tissue organization. Ectopic overexpression of PttPXY and PttCLE41 genes in
      hybrid aspen resulted in vascular tissue abnormalities and poor plant growth. In
      contrast, precise tissue-specific overexpression generated trees that exhibited a
      2-fold increase in the rate of wood formation, were taller, and possessed larger
      leaves compared to the controls. Our results demonstrate that the PXY-CLE pathway
      has evolved to regulate secondary growth and manipulating this pathway can result
      in dramatically increased tree growth and productivity.

PMID- 25866391
TI  - The influence of light on temperature preference in Drosophila.
AB  - Ambient light affects multiple physiological functions and behaviors, such as
      circadian rhythms, sleep-wake activities, and development, from flies to mammals.
      Mammals exhibit a higher body temperature when exposed to acute light compared to
      when they are exposed to the dark, but the underlying mechanisms are largely
      unknown. The body temperature of small ectotherms, such as Drosophila, relies on
      the temperature of their surrounding environment, and these animals exhibit a
      robust temperature preference behavior. Here, we demonstrate that Drosophila
      prefer a ~1 degrees  higher temperature when exposed to acute light rather than
      the dark. This acute light response, light-dependent temperature preference
      (LDTP), was observed regardless of the time of day, suggesting that LDTP is
      regulated separately from the circadian clock. However, screening of eye and
      circadian clock mutants suggests that the circadian clock neurons posterior
      dorsal neurons 1 (DN1(p)s) and Pigment-Dispersing Factor Receptor (PDFR) play a
      role in LDTP. To further investigate the role of DN1(p)s in LDTP, PDFR in DN1(p)s
      was knocked down, resulting in an abnormal LDTP. The phenotype of the pdfr mutant
      was rescued sufficiently by expressing PDFR in DN1(p)s, indicating that PDFR in
      DN1(p)s is responsible for LDTP. These results suggest that light positively
      influences temperature preference via the circadian clock neurons, DN1(p)s, which
      may result from the integration of light and temperature information. Given that
      both Drosophila and mammals respond to acute light by increasing their body
      temperature, the effect of acute light on temperature regulation may be conserved
      evolutionarily between flies and humans.

PMID- 25866392
TI  - A transcriptomic-phylogenomic analysis of the evolutionary relationships of
      flatworms.
AB  - The interrelationships of the flatworms (phylum Platyhelminthes) are poorly
      resolved despite decades of morphological and molecular phylogenetic studies. The
      earliest-branching clades (Catenulida, Macrostomorpha, and Polycladida) share
      spiral cleavage and entolecithal eggs with other lophotrochozoans.
      Lecithoepitheliata have primitive spiral cleavage but derived ectolecithal eggs.
      Other orders (Rhabdocoela, Proseriata, Tricladida and relatives, and
      Bothrioplanida) all have derived ectolecithal eggs but have uncertain affinities
      to one another. The orders of parasitic Neodermata emerge from an uncertain
      position from within these ectolecithal classes. To tackle these problems, we
      have sequenced transcriptomes from 18 flatworms and 5 other metazoan groups. The
      addition of published data produces an alignment of >107,000 amino acids with
      less than 28% missing data from 27 flatworm taxa in 11 orders covering all major
      clades. Our phylogenetic analyses show that Platyhelminthes consist of the two
      clades Catenulida and Rhabditophora. Within Rhabditophora, we show the earliest
      emerging branch is Macrostomorpha, not Polycladida. We show Lecithoepitheliata
      are not members of Neoophora but are sister group of Polycladida, implying
      independent origins of the ectolecithal eggs found in Lecithoepitheliata and
      Neoophora. We resolve Rhabdocoela as the most basally branching euneoophoran
      taxon. Tricladida, Bothrioplanida, and Neodermata constitute a group that appears
      to have lost both spiral cleavage and centrosomes. We identify Bothrioplanida as
      the long-sought closest free-living sister group of the parasitic Neodermata.
      Among parasitic orders, we show that Cestoda are closer to Trematoda than to
      Monogenea, rejecting the concept of the Cercomeromorpha. Our results have
      important implications for understanding the evolution of this major phylum.

PMID- 25866393
TI  - Metabolic Cycles in Yeast Share Features Conserved among Circadian Rhythms.
AB  - Cell-autonomous circadian rhythms allow organisms to temporally orchestrate their
      internal state to anticipate and/or resonate with the external environment.
      Although ~24-hr periodicity is observed across aerobic eukaryotes, the central
      mechanism has been hard to dissect because few simple models exist, and known
      clock proteins are not conserved across phylogenetic kingdoms. In contrast,
      contributions to circadian rhythmicity made by a handful of post-translational
      mechanisms, such as phosphorylation of clock proteins by casein kinase 1 (CK1)
      and glycogen synthase kinase 3 (GSK3), appear conserved among phyla. These
      kinases have many other essential cellular functions and are better conserved in
      their contribution to timekeeping than any of the clock proteins they
      phosphorylate. Rhythmic oscillations in cellular redox state are another
      universal feature of circadian timekeeping, e.g., over-oxidation cycles of
      abundant peroxiredoxin proteins. Here, we use comparative chronobiology to
      distinguish fundamental clock mechanisms from species and/or tissue-specific
      adaptations and thereby identify features shared between circadian rhythms in
      mammalian cells and non-circadian temperature-compensated respiratory
      oscillations in budding yeast. We find that both types of oscillations are
      coupled with the cell division cycle, exhibit period determination by CK1 and
      GSK3, and have peroxiredoxin over-oxidation cycles. We also explore how
      peroxiredoxins contribute to YROs. Our data point to common mechanisms underlying
      both YROs and circadian rhythms and suggest two interpretations: either certain
      biochemical systems are simply permissive for cellular oscillations (with
      frequencies from hours to days) or this commonality arose via divergence from an
      ancestral cellular clock.

PMID- 25866394
TI  - Factual and Counterfactual Action-Outcome Mappings Control Choice between Goal
      Directed Actions in Rats.
AB  - The capacity to extract causal knowledge from the environment allows us to
      predict future events and to use those predictions to decide on a course of
      action. Although evidence of such causal reasoning has long been described,
      recent evidence suggests that using predictive knowledge to guide decision-making
      in this way is predicated on reasoning about causes in two quite distinct ways:
      choosing an action can be based on the interaction between predictive information
      and the consequences of that action, or, alternatively, actions can be selected
      based on the consequences that they do not produce. The latter counterfactual
      reasoning is highly adaptive because it allows us to use information about both
      present and absent events to guide decision-making. Nevertheless, although there
      is now evidence to suggest that animals other than humans, including rats and
      birds, can engage in causal reasoning of one kind or another, there is currently
      no evidence that they use counterfactual reasoning to guide choice. To assess
      this question, we gave rats the opportunity to learn new action-outcome
      relationships, after which we probed the structure of this learning by presenting
      excitatory and inhibitory cues predicting that the specific outcomes of their
      actions would either occur or would not occur. Whereas the excitors biased choice
      toward the action delivering the predicted outcome, the inhibitory cues
      selectively elevated actions predicting the absence of the inhibited outcome,
      suggesting that rats encoded the counterfactual action-outcome mappings and were
      able to use them to guide choice.

PMID- 25866396
TI  - Direct evidence of swimming demonstrates active dispersal in the sea turtle "lost
      years".
AB  - Although oceanic dispersal in larval and juvenile marine animals is widely
      studied, the relative contributions of swimming behavior and ocean currents to
      movements and distribution are poorly understood [1-4]. The sea turtle "lost
      years" [5] (often referred to as the surface-pelagic [6] or oceanic [7] stage)
      are a classic example. Upon hatching, young turtles migrate offshore and are
      rarely observed until they return to coastal waters as larger juveniles [5].
      Sightings of small turtles downcurrent of nesting beaches and in association with
      drifting organisms (e.g., Sargassum algae) led to this stage being described as a
      "passive migration" during which turtles' movements are dictated by ocean
      currents [5-10]. However, laboratory and modeling studies suggest that dispersal
      trajectories might also be shaped by oriented swimming [11-15]. Here, we use an
      experimental approach designed to directly test the passive-migration hypothesis
      by deploying pairs of surface drifters alongside small green (Chelonia mydas) and
      Kemp's ridley (Lepidochelys kempii) wild-caught turtles, tracking their movements
      via satellite telemetry. We conclusively demonstrate that these turtles do not
      behave as passive drifters. In nearly all cases, drifter trajectories were
      uncharacteristic of turtle trajectories. Species-specific and location-dependent
      oriented swimming behavior, inferred by subtracting track velocity from modeled
      ocean velocity, contributed substantially to individual movement and
      distribution. These findings highlight the importance of in situ observations for
      depicting the dispersal of weakly swimming animals. Such observations, paired
      with information on the mechanisms of orientation, will likely allow for more
      accurate predictions of the ecological and evolutionary processes shaped by
      animal movement.

PMID- 25866395
TI  - The Mechanochemical Cycle of Mammalian Kinesin-2 KIF3A/B under Load.
AB  - The response of motor proteins to external loads underlies their ability to work
      in teams and determines the net speed and directionality of cargo transport. The
      mammalian kinesin-2, KIF3A/B, is a heterotrimeric motor involved in
      intraflagellar transport and vesicle motility in neurons. Bidirectional cargo
      transport is known to result from the opposing activities of KIF3A/B and dynein
      bound to the same cargo, but the load-dependent properties of kinesin-2 are
      poorly understood. We used a feedback-controlled optical trap to probe the
      velocity, run length, and unbinding kinetics of mouse KIF3A/B under various loads
      and nucleotide conditions. The kinesin-2 motor velocity is less sensitive than
      kinesin-1 to external forces, but its processivity diminishes steeply with load,
      and the motor was observed occasionally to slip and reattach. Each motor domain
      was characterized by studying homodimeric constructs, and a global fit to the
      data resulted in a comprehensive pathway that quantifies the principal force
      dependent kinetic transitions. The properties of the KIF3A/B heterodimer are
      intermediate between the two homodimers, and the distinct load-dependent behavior
      is attributable to the properties of the motor domains and not to the neck
      linkers or the coiled-coil stalk. We conclude that the force-dependent movement
      of KIF3A/B differs significantly from conventional kinesin-1. Against opposing
      dynein forces, KIF3A/B motors are predicted to rapidly unbind and rebind,
      resulting in qualitatively different transport behavior from kinesin-1. 

PMID- 25866397
TI  - Connectomics-based analysis of information flow in the Drosophila brain.
AB  - Understanding the overall patterns of information flow within the brain has
      become a major goal of neuroscience. In the current study, we produced a first
      draft of the Drosophila connectome at the mesoscopic scale, reconstructed from
      12,995 images of neuron projections collected in FlyCircuit (version 1.1). Neuron
      polarities were predicted according to morphological criteria, with nodes of the
      network corresponding to brain regions designated as local processing units
      (LPUs). The weight of each directed edge linking a pair of LPUs was determined by
      the number of neuron terminals that connected one LPU to the other. The resulting
      network showed hierarchical structure and small-world characteristics and
      consisted of five functional modules that corresponded to sensory modalities
      (olfactory, mechanoauditory, and two visual) and the pre-motor center. Rich-club
      organization was present in this network and involved LPUs in all sensory
      centers, and rich-club members formed a putative motor center of the brain. Major
      intra- and inter-modular loops were also identified that could play important
      roles for recurrent and reverberant information flow. The present analysis
      revealed whole-brain patterns of network structure and information flow.
      Additionally, we propose that the overall organizational scheme showed
      fundamental similarities to the network structure of the mammalian brain. 

PMID- 25866398
TI  - Diagnostic utility of polysomnography in children less than 2 years of age?

PMID- 25866399
TI  - Recombinant, truncated B. circulans keratanase-II: Description and
      characterisation of a novel enzyme for use in measuring urinary keratan sulphate
      levels via LC-MS/MS in Morquio A syndrome.
AB  - OBJECTIVE: Morquio A syndrome (mucopolysaccharidosis IVA; MPS IVA) is an
      autosomal recessive lysosomal storage disorder caused by deficient N
      acetylgalactosamine-6-sulphatase (GALNS) activity. Early and accurate diagnosis
      of this condition is critical for improved patient outcomes, particularly as
      enzyme replacement therapy has recently become available. An LC-MS/MS assay
      utilising keratan sulphate (KS) disaccharides derived from keratanase-II
      digestion provides a sensitive and specific means for quantitation of urinary KS,
      a screening biomarker for Morquio A (Oguma et al., 2007; Martell et al., 2011).
      To ensure a reliable supply of keratanase-II, we sought to produce a Bacillus
      circulans-derived enzyme via a recombinant approach in Escherichia coli. DESIGN
      AND METHODS: Bioinformatics analysis of the B. circulans keratanase-II enzyme
      identified likely dispensable C-terminal domains amenable to enhancement via
      protein engineering. A truncated form of the enzyme was designed to remove the
      domains predicted to be unnecessary for catalytic activity and detrimental to
      recombinant expression in E. coli. RESULTS: C-terminally truncated, recombinant
      B. circulans keratanase-II was purified to >98% homogeneity and extensively
      characterised, demonstrating desired activity, specificity and utility in LC-MS
      based quantitation of urinary KS from Morquio A and control samples, and is
      functionally indistinguishable from full-length, native B. circulans-derived
      keratanase-II. CONCLUSIONS: This novel, recombinant keratanase-II meets all
      performance requirements and can be produced in a rapid and reproducible manner.
      We speculate that other related bacterial enzymes of biomedical or industrial
      interest may be amenable to similar engineered enhancements.

PMID- 25866400
TI  - A novel (A)gammadeltabeta(0)-thalassemia caused by DNA deletion-inversion
      insertion of the beta-globin gene cluster and five olfactory receptor genes:
      Genetic interactions, hematological phenotypes and molecular characterization.
AB  - OBJECTIVE: To report the phenotypes and genetic basis of a novel
      (A)gammadeltabeta(0)-thalassemia found in Thai individuals with several forms of
      thalassemia. DESIGNS AND METHODS: An initial study was done in an adult Thai
      woman who had hypochromic microcytic red cells with unusually 100% Hb F. Extended
      study was carried out on her parents and another 17 unrelated individuals with
      elevated Hb F. Hb analysis was performed by capillary electrophoresis and DNA
      analysis was done using PCR. A novel diagnostic method based on multiplex PCR
      assays was developed. RESULTS: DNA analysis of the proband revealed the
      homozygosity for a novel deletion of 118.3 kb, removing the entire (A)gamma,
      psibeta, delta-, beta-globin and five olfactory receptor (OR) genes with an
      insertion of a 179 bp inverted DNA sequence located behind the OR52A5 gene
      located downstream and an insertion of 7 orphan nucleotides. Her parents were
      both carriers of this mutation. Further screening in suspected cases in our
      series unexpectedly led to identification of an additional 17 cases with this
      mutation in different genotypes including plain heterozygote, homozygote,
      compound heterozygote with Hb E, and double heterozygote with several forms of
      alpha-thalassemia. Hematological features associated with these genetic
      interactions are presented. CONCLUSIONS: Haplotype analysis indicated a single
      origin of this novel deletion-inversion-insertion (A)gammadeltabeta(0)
      thalassemia in the Thai population. Differentiation of this mutation and other
      high Hb F determinants documented previously could be done by using a developed
      multiplex PCR assay.

PMID- 25866401
TI  - Gamma delta T-cell differentiation and effector function programming, TCR signal
      strength, when and how much?
AB  - gammadelta T-cells boast an impressive functional repertoire that can paint them
      as either champions or villains depending on the environmental and immunological
      cues. Understanding the function of the various effector gammadelta subsets
      necessitates tracing the developmental program of these subsets, including the
      point of lineage bifurcation from alphabeta T-cells. Here, we review the
      importance of signals from the T-cell receptor (TCR) in determining alphabeta
      versus gammadelta lineage fate, and further discuss how the molecular components
      of this pathway may influence the developmental programming of gammadelta T-cells
      functional subsets. Additionally, we discuss the role of temporal windows in
      restricting the development of IL-17 producing gammadelta T-cell subtypes, and
      explore whether fetal and adult hematopoietic progenitors maintain the same
      potential for giving rise to this important subset. 

PMID- 25866402
TI  - A case of stranded Indo-Pacific bottlenose dolphin (Tursiops aduncus) with
      lobomycosis-like skin lesions in Kinko-wan, Kagoshima, Japan.
AB  - Lobomycosis is a chronic fungal disease caused by the etiologic agent, Lacazia
      loboi, in the skin and subcutaneous tissues in humans and dolphins in tropical
      and transitional tropical climates. An Indo-Pacific bottlenose dolphin (Tursiops
      aduncus) stranded in Kagoshima, Japan, had severe skin lesions characterized by
      granulomatous reactions and hyperkeratosis that were similar to those of the
      lobomycosis, but no fungal organism was observed in the skin lesion. In this
      paper, we report a stranded Indo-Pacific bottlenose dolphin with lobomycosis-like
      lesions based on pathological examinations in Japan. 

PMID- 25866403
TI  - Immunoreactivity and morphological changes of bursal follicles in chickens
      infected with vaccine or wild-type strains of the infectious bursal disease
      virus.
AB  - Infectious bursal disease (IBD) is characterized by immunosuppression due to the
      depletion of lymphocytes in the atrophied bursa of Fabricius (BF). We have
      sometimes encountered contradictory findings: chickens infected with the vaccine
      IBD virus (IBDV) strain have sometimes exhibited a highly atrophied BF, but not
      immunosuppression. In this study, chickens administered vaccine or wild-type
      strains of IBDV were later vaccinated with the B1 strain of the Newcastle disease
      virus (NDV). Bursal changes were examined histologically with a focus on the
      bursal follicle. The immunoreactivity to NDV was also evaluated with the
      hemagglutination inhibition test. In gross examination, we observed a few
      chickens with a severely atrophied BF in vaccine strain-administered groups
      (vaccine groups), and the level of severity was the same as that in the wild-type
      strain-administered group (wild-type group). However, these chickens retained
      humoral antibody responses to NDV and were revealed to possess a higher number of
      bursal follicles than those of the wild-type group. These results indicated that
      macroscopic evaluation dose not accurately reflect the immunoreactivity and
      degree of bursal damage in IBDV-administered chickens. We also found non
      immunosuppressed chickens in the wild-type group. These non-immunosuppressed
      chickens retained a significantly higher number of normal follicles and total
      follicles according to our statistical analysis. Furthermore, a high correlation
      coefficient between the NDV-HI titer and the number of normal follicles was found
      in the wild-type group. These results implied that the retained number of normal
      follicles is important for the immunoreactivity of chickens infected with IBDV. 

PMID- 25866404
TI  - Lipoprotein cholesterol and triglyceride concentrations associated with dog body
      condition score; effect of recommended fasting duration on sample concentrations
      in Japanese private clinics.
AB  - The objectives of this study were to survey clinics' guidance about recommended
      fasting duration (FD) prior to lipoprotein analysis, and to characterize
      lipoprotein cholesterol and triglyceride concentrations in obese and overweight
      dogs categorized on the basis of the 5-point body condition score (BCS) scale. A
      dataset was created from lipoprotein analysis medical records of 1,538 dogs from
      75 breeds in 354 clinics from 2012 to 2013. A phone survey was conducted to
      obtain the clinics' FD. Two-level linear mixed-effects models were applied to the
      data. Over 50% of the clinics said they recommended fasting for 12 hr or more.
      Dogs in clinics with FD 12 hr or more had lower chylomicron triglyceride
      concentrations than those in clinics with FD less than 8 hr (P=0.05). Mean (+/-
      SEM) BCS at sampling was 3.7 +/- 0.02. Obese and overweight dogs had higher very
      low density lipoprotein (VLDL) and high density lipoprotein (HDL) cholesterol and
      triglyceride concentrations than ideal dogs (P<0.05), but no such difference was
      found for low density lipoprotein cholesterol and triglyceride concentrations
      (P>=0.07). Across all BCS, as dog age rose from 0 to 8 years old, HDL cholesterol
      concentrations decreased by 13.5 mg/dl, whereas VLDL triglyceride concentrations
      increased by 81.7 mg/dl (P<0.05). In conclusion, FD of 8 hr or less may affect
      lipoprotein lipid concentrations. Obese and overweight dogs were characterized as
      having high VLDL and HDL cholesterol and triglyceride concentrations.

PMID- 25866405
TI  - Are children with stronger cognitive capacity more or less disturbed by classroom
      noise and dysphonic teachers?
AB  - PURPOSE: This study aimed to explore if dysphonic voice quality affects
      children's performance on a language comprehension test, the Test for Reception
      of Grammar-2 (TROG-2), performed in simultaneous background noise (non-semantic
      babble). A further aim was to investigate the role of Working Memory Capacity
      (WMC) and Executive Functioning (EF) in coping with the voice against a
      background of babble conditions. METHOD: Ninety-three mainstreamed 8 year old
      children with typical language development were tested for WMC and EF. Two groups
      of children (n = 47/46) were formed and presented with recordings of TROG-2
      instructions read by one female speaker: one group was presented with recordings
      with induced dysphonic voice quality, the other with recordings of typical voice.
      Both groups listened to the voice recordings in competing babble noise at a
      Signal-to-Noise Ratio of + 10 dB. RESULT: Significant differences were found for
      the interaction between cognitive capacity and the TROG-2 results in relation to
      the voice conditions. In the dysphonic voice condition, children with better WMC
      results scored higher at the easier comprehension tasks. In the typical voice
      condition, children with better WMC and EF results scored higher on the more
      difficult tasks. Seventeen per cent of the variance for the TROG-2 results was
      explained by the WMC and EF results. There was no overall effect on the
      children's performance depending of voice condition. CONCLUSION: The effect of
      the speaker's voice quality on children's performance varies depending on the
      prevalence of background babble noise and on the task demands. The dysphonic
      voice and babble noise seem to demand allocation of cognitive capacities at the
      cost of language comprehension.

PMID- 25866406
TI  - Intrabiliary growth of colorectal liver metastases.

PMID- 25866407
TI  - Regenerative multiple hepatic nodular hyperplasia associated with oxalyplatin.

PMID- 25866408
TI  - Characterization of novel avian paramyxovirus strain APMV/Shimane67 isolated from
      migratory wild geese in Japan.
AB  - An avian paramyxovirus (APMV) isolated from goose feces (APMV/Shimane67) was
      biologically, serologically and genetically characterized. APMV/Shimane67 showed
      typical paramyxovirus morphology on electron microscopy. On hemagglutination
      inhibition test, antiserum against APMV/Shimane67 revealed low reactivity with
      other APMV serotypes and vice versa. The fusion (F) protein gene of
      APMV/Shimane67 contained 1,638 nucleotides in a single open reading frame
      encoding a protein of 545 amino acids. The cleavage site of F protein contained a
      pair of single basic amino acid (VRENR/L). The nucleotide and deduced amino acid
      sequences of the F gene of APMV/Shimane67 had relatively low identities (42.9
      62.7% and 28.9-67.3%, respectively) with those of other APMVs. Phylogenetic
      analysis showed that APMV/Shimane67 was related to NDV, APMV-9 and APMV-12, but
      was distinct from those APMV serotypes. These results suggest that APMV/Shimane67
      is a new APMV serotype, APMV-13.

PMID- 25866409
TI  - Prevalence of porcine reproductive and respiratory syndrome virus detection in
      aborted fetuses, mummified fetuses and stillborn piglets using quantitative
      polymerase chain reaction.
AB  - The objective of the present study was to investigate the prevalence of porcine
      reproductive and respiratory syndrome (PRRS) virus detection in aborted fetuses
      (n=32), mummified fetuses (n=30) and stillborn piglets (n=27) from 10 swine herds
      in Thailand using quantitative polymerase chain reaction (qPCR). Pooled organs
      and umbilical cord from each fetus/piglet were homogenized and subjected to RNA
      extraction and cDNA synthesis. The qPCR was carried out on the ORF7 of the PRRS
      viral genome using fluorogenic probes for amplified product detection. The
      results revealed that 67.4% (60/89) of the specimens contained PRRS virus. The
      virus was found in 65.6% (21/32) of aborted fetuses, 63.3% (19/30) of mummified
      fetuses and 74.1% (20/27) of stillborn piglets (P=0.664). Genotype 1, genotype 2
      and mixed genotypes of PRRS virus were detected in 19.1% (17/89), 25.8% (23/89)
      and 22.5% (20/89) of the specimens, respectively (P=0.316). PRRS virus antigen
      was retrieved from both non-PRRS-vaccinated herds (68.2%, 45/66) and PRRS
      vaccinated herds (65.2%, 15/23) (P=0.794). These findings indicated that these
      specimens are important sources of the PRRS viral load and the viral shedding
      within the herd. Thus, intensive care on the routine management of dead fetuses
      and stillborn piglets in PRRS virus-positive herds should be emphasized.

PMID- 25866410
TI  - Blood biochemical values in Japanese Black breeding cows in Kagoshima Prefecture,
      Japan.
AB  - To obtain blood biochemical basic data of Japanese Black breeding cows in
      Kagoshima Prefecture, Japan, blood samples were obtained from 857 clinically
      healthy multiparous cows on 71 farms. Cows were divided into three stages: the
      prepartum stage (between 20 and 80 days before parturition, n=290), lactation
      stage (between 20 and 80 days after parturition, n=283) and maintenance stage
      (between 120 and 200 days after parturition, n=284). The mean concentration of
      total protein and total cholesterol, and the mean activities of aspartate
      aminotransferase in the lactation stage tended to be higher than those in the
      prepartum and maintenance stages. The mean concentration of glucose in the
      prepartum stage tended to be lower than that in the lactation and the maintenance
      stages. The mean concentration of nonesterified fatty acids and beta
      hydroxybutyrate in the prepartum stage tended to be higher than those in the
      lactation and maintenance stages. The mean concentration of serum retinol was
      approximately 30 ug/dl in all stages. These results suggest that the blood
      biochemical values of multiparous Japanese Black cows vary with breeding stages,
      and it is considered that the blood parameters obtained in this study are useful
      as indices for health management of Japanese Black breeding cows.

PMID- 25866411
TI  - Development and Characterization of Biphasic Hydroxyapatite/beta-TCP Cements.
AB  - Biphasic calcium phosphate bioceramics composed of hydroxyapatite (HA) and beta
      tricalcium phosphate (beta-TCP) have relevant properties as synthetic bone
      grafts, such as tunable resorption, bioactivity, and intrinsic osteoinduction.
      However, they have some limitations associated to their condition of high
      temperature ceramics. In this work self-setting Biphasic Calcium Phosphate
      Cements (BCPCs) with different HA/beta-TCP ratios were obtained from self-setting
      alpha-TCP/beta-TCP pastes. The strategy used allowed synthesizing BCPCs with
      modulated composition, compressive strength, and specific surface area. Due to
      its higher solubility, alpha-TCP was fully hydrolyzed to a calcium-deficient HA
      (CDHA), whereas beta-TCP remained unreacted and completely embedded in the CDHA
      matrix. Increasing amounts of the non-reacting beta-TCP phase resulted in a
      linear decrease of the compressive strength, in association to the decreasing
      amount of precipitated HA crystals, which are responsible for the mechanical
      consolidation of apatitic cements. Ca2+ release and degradation in acidic medium
      was similar in all the BCPCs within the timeframe studied, although differences
      might be expected in longer term studies once beta-TCP, the more soluble phase
      was exposed to the surrounding media.

PMID- 25866412
TI  - Testing Ecological Theories of Offender Spatial Decision Making Using a Discrete
      Choice Model.
AB  - Research demonstrates that crime is spatially concentrated. However, most
      research relies on information about where crimes occur, without reference to
      where offenders reside. This study examines how the characteristics of
      neighborhoods and their proximity to offender home locations affect offender
      spatial decision making. Using a discrete choice model and data for detected
      incidents of theft from vehicles (TFV), we test predictions from two theoretical
      perspectives-crime pattern and social disorganization theories. We demonstrate
      that offenders favor areas that are low in social cohesion and closer to their
      home, or other age-related activity nodes. For adult offenders, choices also
      appear to be influenced by how accessible a neighborhood is via the street
      network. The implications for criminological theory and crime prevention are
      discussed.

PMID- 25866413
TI  - MORTALITY, THE FAMILY AND THE INDIAN OCEAN TSUNAMI.
AB  - Over 130,000 people died in the 2004 Indian Ocean tsunami. The correlates of
      survival are examined using data from the Study of the Tsunami Aftermath and
      Recovery (STAR), a population-representative survey collected in Aceh and North
      Sumatra, Indonesia, before and after the tsunami. Children, older adults and
      females were the least likely to survive. Whereas socio-economic factors mattered
      relatively little, the evidence is consistent with physical strength playing a
      role. Pre-tsunami household composition is predictive of survival and suggests
      that stronger members sought to help weaker members: men helped their wives,
      parents and children, while women helped their children.

PMID- 25866414
TI  - Isotopic analysis of island House Martins Delichon urbica indicates marine
      provenance of nutrients.
AB  - The presence of one of the largest colonies of House Martins in Europe on the
      small island of Stora Karlso, Sweden, led us to investigate the source of their
      food by analysis of stable isotopes of carbon and nitrogen. Carbon isotopic
      values of House Martin nestlings were the same as those of Common Guillemot Uria
      aalge nestlings fed on marine fish, but differed from local Collared Flycatcher
      Ficedula albicollis nestlings fed on woodland insects. We infer that these House
      Martins fed their chicks almost exclusively on insects that had used nutrients
      derived from seabirds, indicating a dependence on the presence of a large seabird
      colony. We suggest by extension that some populations of island passerines of
      high conservation importance may also be dependent on nutrient subsidies from
      seabird colonies.

PMID- 25866415
TI  - Changing Attitudes Toward Care of Aging Parents: The Influence of Education,
      International Travel, and Gender.
AB  - Population aging is a key public health issue facing many nations, and is
      particularly pronounced in many Asian countries. At the same time, attitudes
      toward filial obligation are also rapidly changing, with a decreasing sense that
      children are responsible for caring for elderly parents. This investigation
      blends the family versus nonfamily mode of social organization framework with a
      life course perspective to provide insight into the processes of ideational
      change regarding filial responsibility, highlighting the influence of education
      and international travel. Using data from a longitudinal study in Nepal-the
      Chitwan Valley Family Study-results demonstrate that education and international
      travel are associated with a decrease in attitudes toward filial obligation.
      However, findings further reveal that the impact of education and international
      travel vary both across the life course and by gender.

PMID- 25866416
TI  - Membrane adsorbers comprising grafted glycopolymers for targeted lectin binding.
AB  - This work details the design and testing of affinity membrane adsorbers for
      lectin purifications that incorporate glucose-containing glycopolymers. It is the
      selective interaction between the sugar residues of the glycopolymer and the
      complementary carbohydrate-binding domain of the lectin that provides the basis
      for the isolation and purification of lectins from complex biological media. The
      design approach used in these studies was to graft glycopolymer 'tentacles' from
      macroporous regenerated cellulose membranes by atom transfer radical
      polymerization. As shown in earlier studies, this design approach can be used to
      prepare high-productivity membrane adsorbers. The model lectin, concanavalin A
      (conA), was used to evaluate membrane performance in bind-and-elute purification,
      using a low molecular weight sugar for elution. The membrane capacity for binding
      conA was measured at equilibrium and under dynamic conditions using flow rates of
      0.1 and 1.0 mL/min. The first Damkohler number was estimated to relate the
      adsorption rate to the convective mass transport rate through the membrane bed.
      It was used to assess whether adsorption kinetics or mass transport contributed
      the primary limitation to conA binding. Analyses indicate that this system is not
      limited by the accessibility of the binding sites, but by the inherent rate of
      adsorption of conA onto the glycopolymer.

PMID- 25866417
TI  - Building Kindergartners' Number Sense: A Randomized Controlled Study.
AB  - Math achievement in elementary school is mediated by performance and growth in
      number sense during kindergarten. The aim of the present study was to test the
      effectiveness of a targeted small group number sense intervention for high-risk
      kindergartners from low-income communities. Children were randomly assigned to
      one of three groups (n = 44 in each group): a number sense intervention group, a
      language intervention group, or a business as usual control group. Accounting for
      initial skill level in mathematical knowledge, children who received the number
      sense intervention performed better than controls at immediate post test, with
      meaningful effects on measures of number competencies and general math
      achievement. Many of the effects held eight weeks after the intervention was
      completed, suggesting that children internalized what they had learned. There
      were no differences between the language and control groups on any math-related
      measures.

PMID- 25866418
TI  - Burglar Target Selection: A Cross-national Comparison.
AB  - OBJECTIVES: This study builds on research undertaken by Bernasco and Nieuwbeerta
      and explores the generalizability of a theoretically derived offender target
      selection model in three cross-national study regions. METHODS: Taking a discrete
      spatial choice approach, we estimate the impact of both environment- and offender
      level factors on residential burglary placement in the Netherlands, the United
      Kingdom, and Australia. Combining cleared burglary data from all study regions in
      a single statistical model, we make statistical comparisons between environments.
      RESULTS: In all three study regions, the likelihood an offender selects an area
      for burglary is positively influenced by proximity to their home, the proportion
      of easily accessible targets, and the total number of targets available.
      Furthermore, in two of the three study regions, juvenile offenders under the
      legal driving age are significantly more influenced by target proximity than
      adult offenders. Post hoc tests indicate the magnitudes of these impacts vary
      significantly between study regions. CONCLUSIONS: While burglary target selection
      strategies are consistent with opportunity-based explanations of offending, the
      impact of environmental context is significant. As such, the approach undertaken
      in combining observations from multiple study regions may aid criminology
      scholars in assessing the generalizability of observed findings across multiple
      environments.

PMID- 25866419
TI  - Silver Vanadium Diphosphate Ag2VP2O8: Electrochemistry and Characterization of
      Reduced Material providing Mechanistic Insights.
AB  - Silver vanadium phosphorous oxides (AgwVxPyOz) are notable battery cathode
      materials due to their high energy density and demonstrated ability to form in
      situ Ag metal nanostructured electrically conductive networks within the cathode.
      While analogous silver vanadium diphosphate materials have been prepared,
      electrochemical evaluations of these diphosphate based materials have been
      limited. We report here the first electrochemical study of a silver vanadium
      diphosphate, Ag2VP2O8, where the structural differences associated with
      phosphorous oxides versus diphosphates profoundly affect the associated
      electrochemistry. Reminiscent of Ag2VO2PO4 reduction, in-situ formation of silver
      metal nanoparticles was observed with reduction of Ag2VP2O8. However, counter to
      Ag2VO2PO4 reduction, Ag2VP2O8 demonstrates a significant decrease in conductivity
      upon continued electrochemical reduction. Structural analysis contrasting the
      crystallography of the parent Ag2VP2O8 with that of the proposed Li2VP2O8
      reduction product is employed to gain insight into the observed electrochemical
      reduction behavior, where the structural rigidity associated with the diphosphate
      anion may be associated with the observed particle fracturing upon deep
      electrochemical reduction. Further, the diphosphate anion structure may be
      associated with the high thermal stability of the partially reduced Ag2VP2O8
      materials, which bodes well for enhanced safety of batteries incorporating this
      material.

PMID- 25866420
TI  - Den Entry Behavior in Scandinavian Brown Bears: Implications for Preventing Human
      Injuries.
AB  - Encounters between Scandinavian brown bears (Ursus arctos) and humans that result
      in human injuries and fatalities typically coincide with den entry in October and
      November, and commonly occur near a den. Our aim was to determine when bears
      arrive at their dens, identify potential predictors of this event, document
      behavior and activity associated with this period, and attempt to explain the
      increased risk of bear-caused human injuries in this period. We analyzed global
      positioning system (GPS) location and activity data from brown bears in south
      central Sweden, using generalized linear mixed models, statistical process
      control, and activity analyses. Bears arrived at their den sites between 6
      October and 1 December. Timing varied by reproductive category, bear age, and
      year. Half of all bears significantly reduced their activity before arriving at
      the den area: on average 2,169 m away from the den and 1.8 days before arrival.
      The other half reduced their activity after arriving at the den area. The latter
      bears took longer time to reach hibernation activity levels, but we did not find
      a difference in the start date of hibernation between the 2 groups. Bears also
      appeared to be sensitive to disturbance in this period, with higher den
      abandonment rates than later in winter, particularly for males and for bears that
      had not visited their den sites previously. Den entry occurred from October to
      December, with high variability and poor predictability of its timing. Therefore,
      restricting hunting or other recreation activities to reduce risk of injury by
      bears and disturbing bears probably would be both impractical and ineffective.
      Our findings can be used to educate hunters about bear behavior at this time of
      year. Many people associate dens with an increased risk of a bear responding
      aggressively to disturbance to defend its den, but our results indicate that
      other behavioral, and possibly physiological, changes in this period also may be
      involved. (c) 2014 The Authors. The Journal of Wildlife Management published by
      The Wildlife Society.

PMID- 25866421
TI  - Employment, Social Networks and Undocumented Migrants: The Employer Perspective.
AB  - This article draws on data from qualitative interviews with ethnic enclave and
      ethnic economy business entrepreneurs from Chinese, Bangladeshi and Turkish
      speaking communities in London. Routes into business and worker recruitment
      practices are explored, demonstrating the centrality of social capital in the
      form of family and other social networks within these processes. The article
      investigates what employers consider the desirable characteristics of workers:
      trust, kinship, gender, social networks, language compatibility and the needs of
      the business intersect with racialised notions of workers' strengths and
      characteristics. Finally, we consider changing practices in relation to the
      employment of undocumented migrants, in the context of an increasingly punitive
      legislative regime. The complex and variable impact of policy alongside the ways
      in which other obligations and positions outweigh the fear and risks of sanctions
      associated with non-compliance is revealed.

PMID- 25866422
TI  - Species-specific separation of lake plankton reveals divergent food assimilation
      patterns in rotifers.
AB  - 1. The analysis of functional groups with a resolution to the individual species
      level is a basic requirement to better understand complex interactions in aquatic
      food webs. Species-specific stable isotope analyses are currently applied to
      analyse the trophic role of large zooplankton or fish species, but technical
      constraints complicate their application to smaller-sized plankton. 2. We
      investigated rotifer food assimilation during a short-term microzooplankton bloom
      in the East African soda lake Nakuru by developing a method for species-specific
      sampling of rotifers. 3. The two dominant rotifers, Brachionus plicatilis and
      Brachionus dimidiatus, were separated to single-species samples (purity >95%) and
      significantly differed in their isotopic values (4.10/00 in delta13C and 1.50/00
      in delta15N). Bayesian mixing models indicated that isotopic differences were
      caused by different assimilation of filamentous cyanobacteria and particles <2
      MUm and underlined the importance of species-specific sampling of smaller
      plankton compartments. 4. A main difference was that the filamentous
      cyanobacterium Arthrospira fusiformis, which frequently forms blooms in African
      soda lakes, was an important food source for the larger-sized B. plicatilis
      (48%), whereas it was hardly ingested by B. dimidiatus. Overall, A. fusiformis
      was, relative to its biomass, assimilated to small extents, demonstrating a high
      grazing resistance of this species. 5. In combination with high population
      densities, these results demonstrate a strong potential of rotifer blooms to
      shape phytoplankton communities and are the first in situ demonstration of a
      quantitatively important direct trophic link between rotifers and filamentous
      cyanobacteria.

PMID- 25866423
TI  - Constructing Couples' Stories: Narrative Practice Insights from a Dyadic Dementia
      Intervention.
AB  - Memory loss and dementia can be devastating for both caregivers and care
      recipients. Narrative therapeutic approaches offer promise, as well as
      challenges, for social interventions with couples where one partner has dementia.
      The Couples Life Story Approach is a recently-developed method by which
      practitioners work with such couples to help them narrate the story of their life
      together. This narrative approach is augmented by mementoes (e.g., photos, cards)
      that are collected by the couple during the intervention. Significant memories
      are elicited from both partners and developed into a Life Story Book. Drawing on
      data from this clinical research intervention with 20 older couples, we ask: What
      are some of the challenges of conducting narrative-based therapeutic
      interventions with older couples with memory loss? Clinical themes were
      identified utilizing a multiple case study approach during weekly team meetings.
      Six of the most prominent themes are presented here. Specifically, how to: (1)
      construct a narrative from disparate stories, (2) tell a mutual story, (3) tell
      the story of a couple that has been in a shorter relationship, (4) incorporate
      others in the story, (5) include difficult life moments, and, (6) end the story.
      Within each theme, we utilize case examples to illuminate relevant issues and
      describe strategies that were developed to resolve these clinical challenges.
      Implications for practitioners and clinical researchers who are engaged in dyadic
      interventions are discussed.

PMID- 25866424
TI  - Ready to Lead, But How? Teachers' Experiences in High-poverty Urban Schools.

PMID- 25866425
TI  - The Pharmaceutical Commons: Sharing and Exclusion in Global Health Drug
      Development.
AB  - In the last decade, the organization of pharmaceutical research on neglected
      tropical diseases has undergone transformative change. In a context of perceived
      "market failure," the development of new medicines is increasingly handled by
      public-private partnerships. This shift toward hybrid organizational models
      depends on a particular form of exchange: the sharing of proprietary assets in
      general and of intellectual property rights in particular. This article explores
      the paradoxical role of private property in this new configuration of global
      health research and development. Rather than a tool to block potential
      competitors, proprietary assets function as a lever to attract others into risky
      collaborative ventures; instead of demarcating public and private domains, the
      sharing of property rights is used to increase the porosity of that boundary.
      This reimagination of the value of property is connected to the peculiar
      timescape of global health drug development, a promissory orientation to the
      future that takes its clearest form in the centrality of "virtual" business
      models and the proliferation of strategies of deferral. Drawing on the
      anthropological literature on inalienable possessions, we reconsider property's
      traditional exclusionary role and discuss the possibility that the new
      pharmaceutical "commons" proclaimed by contemporary global health partnerships
      might be the precursor of future enclosures.

PMID- 25866426
TI  - Can Professional Environments in Schools Promote Teacher Development? Explaining
      Heterogeneity in Returns to Teaching Experience.
AB  - Although wide variation in teacher effectiveness is well established, much less
      is known about differences in teacher improvement over time. We document that
      average returns to teaching experience mask large variation across individual
      teachers and across groups of teachers working in different schools. We examine
      the role of school context in explaining these differences using a measure of the
      professional environment constructed from teachers responses to state-wide
      surveys. Our analyses show that teachers working in more supportive professional
      environments improve their effectiveness more over time than teachers working in
      less supportive contexts. On average, teachers working in schools at the 75th
      percentile of professional environment ratings improved 38% more than teachers in
      schools at the 25th percentile after 10 years.

PMID- 25866427
TI  - Youth Mentoring Relationships in Context: Mentor Perceptions of Youth,
      Environment, and the Mentor Role.
AB  - Youth mentoring is primarily understood as a relationship between mentor and
      mentee, yet mentors often enter into home, school, and other community settings
      associated with youth they serve, and interact regularly with other people in
      mentees' lives. Understanding how and why mentors negotiate their role as they do
      remains underexplored, especially in relation to these environmental elements.
      This qualitative study drew on structured interviews conducted with professional
      mentors (N = 9) serving youth at risk for adjustment problems to examine how
      mentors' perceptions of their mentees and mentee environments informed their
      sense of how they fulfilled the mentoring role. Mentors commonly characterized
      problems youth displayed as byproducts of adverse environments, and individual
      level strengths as existing "in spite of" environmental inputs. Perceptions of
      mentees and their environments informed mentors' role conceptualizations, with
      some mentors seeing themselves as antidotes to environmental adversity. Mentors
      described putting significant time and effort into working closely with other key
      individuals as well as one-on-one with mentees because they identified
      considerable environmental need; however, extra-dyadic facets of their roles were
      far less clearly defined or supported. They described challenges associated with
      role overload and opaque role boundaries, feeling unsupported by other adults in
      mentees' lives, and frustrated by the prevalence of risks. Community-based
      mentoring represents a unique opportunity to connect with families, but mentors
      must be supported around the elements of their roles that extend beyond mentor
      mentee relationships in order to capitalize more fully on the promise of the
      intervention.

PMID- 25866428
TI  - Fathers Matter: Involving and Engaging Fathers in the Child Welfare System
      Process.
AB  - Research suggests that children with involved and engaged fathers tend to have
      more positive outcomes relative to physical, cognitive, and social emotional
      health. Of children who become involved in the child welfare system, involving
      multiple parents in the case (e.g. mother and father) often results in a greater
      chance of a child returning home, fewer placement episodes, and reduced trauma
      that may be caused by separation anxiety. With the rise of single parenting homes
      (which are mostly maternal) in the United States, child welfare agencies are
      examining the efficacy of engaging multiple caregivers (esp. fathers) in the
      child welfare process. Research suggests that in order to involve fathers in
      child welfare processes, practices and policies must be intentional in
      implementing systems and protocols that encourage involvement of all parents
      regardless of relationship status of the parents. However, few child welfare
      agencies are required to inquire about fathers or involve fathers in the child's
      case. The purpose of this paper is to highlight efforts of the Connecticut
      Comprehensive Outcome Review (CCOR) process and discuss challenges and lessons
      learned from interviews and listening forums/focus groups that included social
      workers and fathers who are involved in the child welfare system in the state of
      Connecticut. Recommendations and considerations on engaging and involving fathers
      are discussed.

PMID- 25866429
TI  - Application of a new xylanase activity from Bacillus amyloliquefaciens XR44A in
      brewer's spent grain saccharification.
AB  - BACKGROUND: Cellulases and xylanases are the key enzymes involved in the
      conversion of lignocelluloses into fermentable sugars. Western Ghat region
      (India) has been recognized as an active hot spot for the isolation of new
      microorganisms. The aim of this work was to isolate new microorganisms producing
      cellulases and xylanases to be applied in brewer's spent grain saccharification.
      RESULTS: 93 microorganisms were isolated from Western Ghat and screened for the
      production of cellulase and xylanase activities. Fourteen cellulolytic and seven
      xylanolytic microorganisms were further screened in liquid culture. Particular
      attention was focused on the new isolate Bacillus amyloliquefaciens XR44A,
      producing xylanase activity up to 10.5 U mL-1. A novel endo-1,4-beta xylanase was
      identified combining zymography and proteomics and recognized as the main enzyme
      responsible for B. amyloliquefaciens XR44A xylanase activity. The new xylanase
      activity was partially characterized and its application in saccharification of
      brewer's spent grain, pretreated by aqueous ammonia soaking, was investigated.
      CONCLUSION: The culture supernatant of B. amyloliquefaciens XR44A with xylanase
      activity allowed a recovery of around 43% xylose during brewer's spent grain
      saccharification, similar to the value obtained with a commercial xylanase from
      Trichoderma viride, and a maximum arabinose yield of 92%, around 2-fold higher
      than that achieved with the commercial xylanase. (c) 2014 The Authors. Journal of
      Chemical Technology & Biotechnology published by John Wiley & Sons Ltd on behalf
      of Society of Chemical Industry.

PMID- 25866430
TI  - Developmental plasticity of growth and digestive efficiency in dependence of
      early-life food availability.
AB  - Nutrition is a potent mediator of developmental plasticity. If food is scarce,
      developing organisms may invest into growth to outgrow size-dependent mortality
      (short-term benefit) and/or into an efficient digestion system (long-term
      benefit). We investigated this potential trade-off, by determining the influence
      of food availability on juvenile body and organ growth, and on adult digestive
      efficiency in the cichlid fish Simochromis pleurospilus. We reared two groups of
      fish at constant high or low food rations, and we switched four other groups
      between these two rations at an early and late juvenile period. We measured
      juvenile growth and organ sizes at different developmental stages and determined
      adult digestive efficiency. Fish kept at constant, high rations grew considerably
      faster than low-food fish. Nevertheless, S. pleurospilus partly buffered the
      negative effects of low food availability by developing heavier digestive organs,
      and they were therefore more efficient in digesting their food as adults. Results
      of fish exposed to a ration switch during either the early or late juvenile
      period suggest (i) that the ability to show compensatory growth after early
      exposure to low food availability persists during the juvenile period, (ii) that
      digestive efficiency is influenced by varying juvenile food availability during
      the late juvenile phase and (iii) that the efficiency of the adult digestive
      system is correlated with the growth rate during a narrow time window of juvenile
      period.

PMID- 25866431
TI  - IS WORK-FAMILY CONFLICT A MULTILEVEL STRESSOR LINKING JOB CONDITIONS TO MENTAL
      HEALTH? EVIDENCE FROM THE WORK, FAMILY AND HEALTH NETWORK.
AB  - PURPOSE: Most research on the work conditions and family responsibilities
      associated with work-family conflict and other measures of mental health uses the
      individual employee as the unit of analysis. We argue that work conditions are
      both individual psychosocial assessments and objective characteristics of the
      proximal work environment, necessitating multilevel analyses of both individual-
      and team-level work conditions on mental health. METHODOLOGY/APPROACH: This study
      uses multilevel data on 748 high-tech professionals in 120 teams to investigate
      relationships between team- and individual-level job conditions, work-family
      conflict, and four mental health outcomes (job satisfaction, emotional
      exhaustion, perceived stress, and psychological distress). FINDINGS: We find that
      work-to-family conflict is socially patterned across teams, as are job
      satisfaction and emotional exhaustion. Team-level job conditions predict team
      level outcomes, while individuals' perceptions of their job conditions are better
      predictors of individuals' work-to-family conflict and mental health. Work-to
      family conflict operates as a partial mediator between job demands and mental
      health outcomes. PRACTICAL IMPLICATIONS: Our findings suggest that organizational
      leaders concerned about presenteeism, sickness absences, and productivity would
      do well to focus on changing job conditions in ways that reduce job demands and
      work-to-family conflict in order to promote employees' mental health.
      ORIGINALITY/VALUE OF THE CHAPTER: We show that both work-to-family conflict and
      job conditions can be fruitfully framed as team characteristics, shared
      appraisals held in common by team members. This challenges the framing of work-to
      family conflict as a "private trouble" and provides support for work-to-family
      conflict as a structural mismatch grounded in the social and temporal
      organization of work.

PMID- 25866432
TI  - Assessment of cell-cycle arrest biomarkers to predict early and delayed acute
      kidney injury.
AB  - PURPOSE: To assess urinary tissue inhibitor of metalloproteinases-2 and insulin
      like growth factor binding protein 7 ([TIMP-2].[IGFBP7]), urinary neutrophil
      gelatinase-associated lipocalin (NGAL), and urinary cystatin-C as acute kidney
      injury predictors (AKI) exploring the association of nonrenal factors with
      elevated biomarker levels. METHODS: We studied 94 patients with urine collected
      within 48 hours of ICU admission and no AKI at sampling. AKI was defined by the
      Kidney Disease: Improving Global Outcomes criteria. Predictive performance was
      assessed by the area under the receiver operating characteristics (ROC) curve.
      Associations between biomarkers and clinical factors were assessed by
      multivariate linear regression. RESULTS: Overall, 19 patients (20%) developed AKI
      within 48 hours. [TIMP-2].[IGFBP7], NGAL, or cystatin-C admission levels did not
      differ between patients without AKI and patients developing AKI. [TIMP
      2].[IGFBP7], NGAL, and cystatin-C were poor AKI predictors (ROC areas 0.34-0.51).
      Diabetes was independently associated with higher [TIMP-2].[IGFBP7] levels (P =
      0.02) but AKI was not (P = 0.24). Sepsis was independently associated with higher
      NGAL (P < 0.001) and cystatin-C (P = 0.003) levels. CONCLUSIONS: Urinary [TIMP
      2].[IGFBP7], NGAL, and cystatin-C should be used cautiously as AKI predictors in
      general ICU patients since urine levels of these biomarkers are affected by
      factors other than AKI and their performance can be poor.

PMID- 25866433
TI  - Twenty-four-hour urine osmolality as a physiological index of adequate water
      intake.
AB  - While associations exist between water, hydration, and disease risk, research
      quantifying the dose-response effect of water on health is limited. Thus, the
      water intake necessary to maintain optimal hydration from a physiological and
      health standpoint remains unclear. The aim of this analysis was to derive a 24 h
      urine osmolality (U(Osm)) threshold that would provide an index of "optimal
      hydration," sufficient to compensate water losses and also be biologically
      significant relative to the risk of disease. Ninety-five adults (31.5 +/- 4.3
      years, 23.2 +/- 2.7 kg.m(-2)) collected 24 h urine, provided morning blood
      samples, and completed food and fluid intake diaries over 3 consecutive weekdays.
      A U(Osm) threshold was derived using 3 approaches, taking into account European
      dietary reference values for water; total fluid intake, and urine volumes
      associated with reduced risk for lithiasis and chronic kidney disease and plasma
      vasopressin concentration. The aggregate of these approaches suggest that a 24 h
      urine osmolality <=500 mOsm.kg(-1) may be a simple indicator of optimal
      hydration, representing a total daily fluid intake adequate to compensate for
      daily losses, ensure urinary output sufficient to reduce the risk of urolithiasis
      and renal function decline, and avoid elevated plasma vasopressin concentrations
      mediating the increased antidiuretic effort.

PMID- 25866434
TI  - Immunohistochemical expression of Survivin and its relationship with cell
      apoptosis and proliferation in ameloblastomas.
AB  - Ameloblastoma behavior is related to the potential of tumor cells to inhibit
      apoptosis and to initiate a proliferative phase. This study was performed to
      compare the immunoexpression of Survivin with Bcl-2, Bax, and Ki-67 and to
      associate them with the histopathological type of each variant of ameloblastoma.
      MATERIAL AND METHODS: Using the World Health Organization (WHO) criteria for
      ameloblastoma, 110 cases were selected. The cases were classified as
      solid/multicystic and unicystic ameloblastomas. Cellular counts of cytoplasmic
      immunoexpression were assessed for cytoplasmic Survivin, Bcl-2, and Bax, while
      the nuclear immunoexpression of Survivin and Ki-67 was assessed using label
      index. RESULTS: Cytoplasmic Survivin and Bcl-2 showed higher percentages of
      immunoexpression in solid multicystic ameloblastomas compared to unicystic
      ameloblastomas (P < 0.05). Bax, Ki-67, and nuclear Survivin were expressed in
      higher percentages in unicystic ameloblastomas. CONCLUSIONS: Cytoplasmic Survivin
      and Bcl-2 immunoexpression levels were elevated in relation to Bax
      immunoexpression, suggesting aggressive ameloblastoma behavior, while Ki-67 and
      nuclear Survivin immunoexpression may be associated with the type of tumor
      morphology that influences cellular counts or with the greater capacity for
      cellular proliferation and tumor growth.

PMID- 25866436
TI  - Comment on "System accuracy evaluation of the GlucoRx Nexus Voice TD-4280 blood
      glucose monitoring system".

PMID- 25866435
TI  - Biomarkers of lung injury in cardiothoracic surgery.
AB  - Diagnosis of pulmonary dysfunction is currently almost entirely based on a vast
      series of physiological changes, but comprehensive research is focused on
      determining biomarkers for early diagnosis of pulmonary dysfunction. Here we
      discuss the use of biomarkers of lung injury in cardiothoracic surgery and their
      ability to detect subtle pulmonary dysfunction in the perioperative period.
      Degranulation products of neutrophils are often used as biomarker since they have
      detrimental effects on the pulmonary tissue by themselves. However, these
      substances are not lung specific. Lung epithelium specific proteins offer more
      specificity and slowly find their way into clinical studies. 

PMID- 25866437
TI  - A Kinetics and Equilibrium Study of Vanadium Dissolution from Vanadium Oxides and
      Phosphates in Battery Electrolytes: Possible Impacts on ICD Battery Performance.
AB  - Silver vanadium oxide (Ag2V4O11, SVO) has enjoyed widespread commercial success
      over the past 30 years as a cathode material for implantable cardiac
      defibrillator (ICD) batteries. Recently, silver vanadium phosphorous oxide
      (Ag2VO2PO4, SVPO) has been studied as possibly combining the desirable thermal
      stability aspects of LiFePO4 with the electrical conductivity of SVO. Further,
      due to the noted insoluble nature of most phosphate salts, a lower material
      solubility of SVPO relative to SVO is anticipated. Thus, the first vanadium
      dissolution studies of SVPO in battery electrolyte solutions are described
      herein. The equilibrium solubility of SVPO was ~5 times less than SVO, with a
      rate constant of dissolution ~3.5 times less than that of SVO. The vanadium
      dissolution in SVO and SVPO can be adequately described with a diffusion layer
      model, as supported by the Noyes-Whitney equation. Cells prepared with vanadium
      treated anodes displayed higher AC impedance and DC resistance relative to
      control anodes. These data support the premise that SVPO cells are likely to
      exhibit reduced cathode solubility and thus less affected by increased cell
      resistance due to cathode solubility compared to SVO based cells.

PMID- 25866438
TI  - A Person-Centered Approach to Financial Capacity Assessment: Preliminary
      Development of a New Rating Scale.
AB  - Financial exploitation and financial capacity issues often overlap when a
      gerontologist assesses whether an older adult's financial decision is an
      autonomous, capable choice. Our goal is to describe a new conceptual model for
      assessing financial decisions using principles of person-centered approaches and
      to introduce a new instrument, the Lichtenberg Financial Decision Rating Scale
      (LFDRS). We created a conceptual model, convened meetings of experts from various
      disciplines to critique the model and provide input on content and structure, and
      select final items. We then videotaped administration of the LFDRS to five older
      adults and had 10 experts provide independent ratings. The LFDRS demonstrated
      good to excellent inter-rater agreement. The LFDRS is a new tool that allows
      gerontologists to systematically gather information about a specific financial
      decision and the decisional abilities in question.

PMID- 25866439
TI  - Trait Emotional Intelligence and Personality: Gender-Invariant Linkages Across
      Different Measures of the Big Five.
AB  - This study investigated if the linkages between trait emotional intelligence
      (trait EI) and the Five-Factor Model of personality were invariant between men
      and women. Five English-speaking samples (N = 307-685) of mostly undergraduate
      students each completed a different measure of the Big Five personality traits
      and either the full form or short form of the Trait Emotional Intelligence
      Questionnaire (TEIQue). Across samples, models predicting global TEIQue scores
      from the Big Five were invariant between genders, with Neuroticism and
      Extraversion being the strongest trait EI correlates, followed by
      Conscientiousness, Agreeableness, and Openness. However, there was some evidence
      indicating that the gender-specific contributions of the Big Five to trait EI
      vary depending on the personality measure used, being more consistent for women.
      Discussion focuses on the validity of the TEIQue as a measure of trait EI and its
      psychometric properties, more generally.

PMID- 25866440
TI  - A Tale of Two Comparative Psychologies: Reply to Commentaries.
AB  - Animal metacognition is a growing area in comparative psychology that raises
      questions about the evolutionary emergence of reflective mind and self-awareness.
      Theoretical discussions are constructive as this area develops. We thank the
      editor for arranging this dialogue and the commentators for contributing to it.
      The dialogue reveals the strong consensus that one must look beyond
      associationism to understand animal metacognition. The target article and the
      commentaries focused on cognitive process and representation, and on detailed
      cognitive analyses of metacognitive phenomena. Accordingly, this theoretical
      dialogue presents the possible outline of a new phase of animal-metacognition
      research.

PMID- 25866441
TI  - Using a narrative- and play-based activity to promote low-income preschoolers'
      oral language, emergent literacy, and social competence.
AB  - This study examined whether a storytelling and story-acting practice (STSA),
      integrated as a regular component of the preschool curriculum, can help promote
      three key dimensions of young children's school readiness: narrative and other
      oral-language skills, emergent literacy, and social competence. A total of 149
      low-income preschoolers (almost all 3- and 4-year-olds) participated, attending
      six experimental and seven control classrooms. The STSA was introduced in the
      experimental classrooms for the entire school year, and all children in both
      conditions were pre- and post-tested on 11 measures of narrative, vocabulary,
      emergent literacy, pretend abilities, peer play cooperation, and self-regulation.
      Participation in the STSA was associated with improvements in narrative
      comprehension, print and word awareness, pretend abilities, self-regulation, and
      reduced play disruption. For almost all these measures, positive results were
      further strengthened by the frequency of participation in storytelling by
      individual children, indicated by number of stories told (NOST). The STSA is a
      structured preschool practice that exemplifies child-centered, play-based, and
      constructivist approaches in early childhood education, and that can operate as a
      curriculum module in conjunction with a variety of different preschool curricula.
      This study confirmed that it can contribute to promoting learning, development,
      and school readiness for low-income and otherwise disadvantaged children.

PMID- 25866443
TI  - 'PULLING UP MYTHS FROM THE ROOT:' DESIGNING AND IMPLEMENTING AN ANTI-RACIST
      CURRICULUM ABOUT THE AFRICAN HERITAGE FOR THIRD GRADERS IN PUERTO RICO.

PMID- 25866442
TI  - Attorneys' Questions and Children's Productivity in Child Sexual Abuse Criminal
      Trials.
AB  - We investigated the links between questions child witnesses are asked in court,
      children's answers, and case outcome. Samples of acquittals and convictions were
      matched on child age, victim-defendant relationship, and allegation count and
      severity. Transcripts were coded for question types, including a previously under
      examined type of potentially suggestive question, declarative questions.
      Children's productivity was conceptualized in a novel way by separating new from
      repeated content and by adjusting the definition based on the linguistic demands
      of the questions. Attorneys frequently used declarative questions, and
      disconcertingly, attorneys who used these and other suggestive questions more
      frequently were more likely to win their case. Open-ended and closed-ended
      questions elicited similar levels of productivity from children, and both
      elicited more productivity compared with suggestive questions. Results highlight
      how conceptualization of questions and answers can influence conclusions, and
      demonstrate the important real-world implications of attorney questioning
      strategies on legal cases with child witnesses.

PMID- 25866444
TI  - The growth of Chlamydomonas reinhardtii as influenced by high CO2 and low O2 in
      flue gas from a silicomanganese smelter.
AB  - The aim of this study was to find an inexpensive and environmentally friendly CO2
      source for growing the hydrogen-producing microalgae Chlamydomonas reinhardtii.
      The effect of different flue gas concentrations from a silicomanganese smelter on
      the growth of these algae at a photon flux density of 200 MUmol photons m-2 s-1
      applied 24 h day-1 was studied. First, the algae were grown in a laboratory at
      1.2, 6.8 and 17.1 % (v/v) pure CO2 gas mixed with fresh air. After 5 days of
      growth, the dry biomass per litre algal culture was slightly higher (17 %) at 6.8
      % CO2 as compared to at 1.2 % CO2. A further increase to 17.1 % CO2 decreased the
      biomass by about 40 %. Then, the flue gas from a silicomanganese smelter was used
      as a CO2 source for growing the algae. The flue gas was characterized by a high
      CO2 concentration (about 17 % v/v), low oxygen concentration (about 4 %), about
      100 ppm NO x and 1 ppm SO2. The culture medium bubbled with undiluted flue gas
      contained about 490 mg L-1 dissolved CO2 and 4.0 mg L-1 dissolved O2, while the
      lowest flue gas concentration contained about 280 mg L-1 CO2 and 7.1 mg L-1 O2.
      Undiluted flue gas (17.4 % CO2) decreased the biomass of the algae by about 40 %
      as compared with 4.8 % pure CO2 gas or flue gas diluted to a concentration of 6.3
      % CO2. Flue gas diluted to give 10.0 % CO2 gave less reduction in the growth of
      the algae (22 %). It was concluded that the high CO2 concentration itself caused
      the growth reduction and not the air pollutants, and the very low O2
      concentrations in the growth medium could not counteract this negative effect.

PMID- 25866445
TI  - The effect of bubble size on the efficiency and economics of harvesting
      microalgae by foam flotation.
AB  - The effect of bubble size and rise velocity on the efficiency of a foam flotation
      microalgae harvesting unit was determined. Three sparger and input airflow
      combinations were used: (1) limewood sparger with constant airflow, (2) ceramic
      flat plate sparger with constant airflow and (3) ceramic flat plate sparger with
      an oscillating airflow. The ceramic sparger with oscillating flow generated the
      smallest bubbles within the liquid pool and the largest bubbles within the foam
      phase. This delivered the highest levels of biomass recovery due to enhanced
      bubble-algae collision and attachment efficiencies. The smaller bubbles generated
      by the ceramic sparger under constant or oscillating airflow had significantly
      faster rise velocities when compared to the larger bubbles produced by the
      limewood spargers. The faster velocities of the smaller bubbles were due to
      momentum transfer to the liquid phase. Analyses of the harvest economics revealed
      that the ceramic flat plate sparger with an oscillating airflow delivered the
      best overall cost-benefit relationship.

PMID- 25866446
TI  - Titanium uptake and incorporation into silica nanostructures by the diatom
      Pinnularia sp. (Bacillariophyceae).
AB  - Diatoms are an ecologically successful group within the phytoplankton, and their
      special feature is a biofabricated silica cell encasement called a frustule.
      These frustules attract interest in material technology, and one potential
      application is to use them in solar cell technology. The silica frustule with its
      nanoscaled pattern is interesting per se, but the utility is enhanced if we
      succeed in incorporating other elements. Titanium is an interesting element
      because its oxide is a semi-conductor with a high band gap. However, doping with
      relevant elements through bioincorporation is challenging, and it is necessary to
      understand the biology involved in element uptake and incorporation. Here we
      present data on bioincorporation of Ti into the silica frustules of the pennate
      diatom Pinnularia sp. (Ehrenberg) and show that the distribution of the
      incorporated Ti is inhomogeneous both between and within valves. More than a
      tenfold increase of Ti in newly synthesised valves was achieved, and increased Ti
      around the pores was confirmed by both EDS and EELS analyses. HAADF STEM
      spectroscopy revealed a grainy surface with amorphous silica particles of 4 to 5
      nm in size. These observations are explained by what is known from the physico
      chemical processes involved in biosilification and frustule formation, looking
      into it from a biological point of view.

PMID- 25866447
TI  - Total Syntheses of Lyconadins: Finding Efficiency and Diversity.
AB  - Lyconadins A-C are important members of the Lycopodium alkaloid family with
      challenging structural features and interesting biological profile. Herein,
      various synthetic strategies and methods for their preparation are summarized
      with the focus on constructive bond formation and our efficient and divergent
      synthesis based on functional group pairing (FGP) strategy.

PMID- 25866448
TI  - Quantifying the quiet epidemic: Diagnosing dementia in late 20th-century Britain.
AB  - During the late 20th century numerical rating scales became central to the
      diagnosis of dementia and helped transform attitudes about its causes and
      prevalence. Concentrating largely on the development and use of the Blessed
      Dementia Scale, I argue that rating scales served professional ends during the
      1960s and 1970s. They helped old age psychiatrists establish jurisdiction over
      conditions such as dementia and present their field as a vital component of the
      welfare state, where they argued that 'reliable modes of diagnosis' were vital to
      the allocation of resources. I show how these arguments appealed to politicians,
      funding bodies and patient groups, who agreed that dementia was a distinct
      disease and claimed research on its causes and prevention should be designated
      'top priority'. But I also show that worries about the replacement of clinical
      acumen with technical and depersonalized methods, which could conceivably be
      applied by anyone, led psychiatrists to stress that rating scales had their
      limits and could be used only by trained experts.

PMID- 25866449
TI  - Food as pharma: marketing nutraceuticals to India's rural poor.
AB  - This commentary sketches out the politics of the expansion of affordable, fast
      moving nutraceutical products into rural India, with a focus on fortified foods
      and beverages. It examines the relationships between industry, government and
      humanitarian organisations that are being forged alongside the development of
      markets for nutraceuticals; the production of evidence and the harnessing of
      science to support nutraceutical companies' claims; the ways in which
      nutraceuticals are being marketed and distributed in rural areas; and the
      concepts of health and well-being that are being promulgated through those
      marketing campaigns. Lastly, it asks what kinds of impact fast-moving
      nutraceuticals are likely to have on the lives of India's rural poor. It
      concludes by questioning how smooth a transition to nutraceutical consumption Big
      Food marketing strategies can really facilitate and how readily low-income
      families seeking to feed their families and safeguard health will actually adopt
      concepts of wellness and internalise micro-nutrient associated risks.

PMID- 25866450
TI  - Roles of lymphocyte kv1.3-channels in the pathogenesis of renal diseases and
      novel therapeutic implications of targeting the channels.
AB  - Delayed rectifier K(+)-channels (Kv1.3) are predominantly expressed in T
      lymphocytes. Based on patch-clamp studies, the channels play crucial roles in
      facilitating the calcium influx necessary to trigger lymphocyte activation and
      proliferation. Using selective channel inhibitors in experimental animal models,
      in vivo studies then revealed the clinically relevant relationship between the
      channel expression and the pathogenesis of autoimmune diseases. In renal
      diseases, in which "chronic inflammation" or "the overstimulation of cellular
      immunity" is responsible for the pathogenesis, the overexpression of Kv1.3
      channels in lymphocytes promotes their cellular proliferation and thus
      contributes to the progression of tubulointerstitial fibrosis. We recently
      demonstrated that benidipine, a potent dihydropyridine calcium channel blocker,
      which also strongly and persistently inhibits the lymphocyte Kv1.3-channel
      currents, suppressed the proliferation of kidney lymphocytes and actually
      ameliorated the progression of renal fibrosis. Based on the recent in vitro
      evidence that revealed the pharmacological properties of the channels, the most
      recent studies have revealed novel therapeutic implications of targeting the
      lymphocyte Kv1.3-channels for the treatment of renal diseases. 

PMID- 25866452
TI  - Aging and Executive Control: Reports of a Demise Greatly Exaggerated.
AB  - I report a series of meta-analyses on aging and executive control. A first set of
      analyses failed to find evidence for specific age-related deficits in tasks of
      selective attention (inhibition of return, negative priming, flanker, and Stroop)
      or tasks tapping local task-shifting costs (reading with distractors is an
      exception) but found evidence for specific age-related deficits in tasks of
      divided attention (dual tasking and global task-shifting costs). The second set
      examined whether executive control explained any age-related variance in complex
      cognition (episodic memory, reasoning, spatial abilities) over and beyond the
      effects of speed and working memory; it did not. Thus, the purported decline in
      executive control with advancing age is clearly not general, and it may
      ultimately play only a small role in explaining age-related deficits in complex
      cognition.

PMID- 25866451
TI  - Expression of chemokine receptors on peripheral blood T cells in children with
      chronic kidney disease.
AB  - Chemokine receptors play a role in leukocyte recruitment, activation, and
      maintaining effector functions and regulate adaptive immune response and
      angiogenesis. The study aimed at flow cytometric analysis of T cell subsets with
      selected surface chemokine receptors (CCR4, CCR5, CCR7, CXCR3, and CXCR4) or
      receptor combination in peripheral blood of children with chronic kidney disease
      (CKD) on hemodialysis (HD). The percentage of T lymphocytes with CD8 and combined
      CD28,CCR7 expression was higher in HD children. The percentage of T lymphocytes
      expressing CCR7, CD28,CCR7, and CXCR4,CD8 was increased in children on
      conservative treatment. Total number (tn) of CXCR4+ cells was reduced in children
      on hemodialysis. The tn of T CXCR3+ cells was lower in children on conservative
      treatment. During HD the percentage of T CD4+ cells was higher and of T CXCR3+
      lymphocytes was lower after HD session as compared to 15 min of session duration.
      During HD tn of T cells with expression of CCR4, CCR5, CCR7, CXCR3, and CXCR4 was
      constant. The alteration of chemokine receptors expression in children with CKD
      occurs early in the development. Diminished expression of CXCR3, CXCR4 on T cells
      in patients with CKD on HD might result in impaired inflammatory response.
      Increased CCR7+ T cell percentage could be responsible for the alteration of
      migration of cells into secondary lymphatic organs. 

PMID- 25866453
TI  - Considering social work assessment of families.
AB  - Since the 1990s the way in which social workers respond to referrals of children
      to Children's Social Care departments has evolved. It has moved through a process
      that 'screens families out' of child protection assessment to a system aiming to
      'screen families in' where necessary, and now uses a holistic assessment aiming
      to screen for both risk and need. The assessment framework developed to assess
      children in need and their families is the modern social work response to all
      referrals. Little research has been carried out to assess its suitability as a
      widespread social work response. This article considers the debates that have
      emerged in relation to its use and concludes that insufficient consideration has
      been given to evaluating assessment as an appropriate measure of need and risk.
      Wider provision of non-assessed universal services would reduce the need for
      assessment.

PMID- 25866454
TI  - A Novel Method of Extraction of Blend Component Structure from SANS Measurements
      of Homopolymer Bimodal Blends.
AB  - A new method is presented for the extraction of single-chain form factors and
      interchain interference functions from a range of small-angle neutron scattering
      (SANS) experiments on bimodal homopolymer blends. The method requires a minimum
      of three blends, made up of hydrogenated and deuterated components with matched
      degree of polymerization at two different chain lengths, but with carefully
      varying deuteration levels. The method is validated through an experimental study
      on polystyrene homopolymer bimodal blends with [Formula: see text]. By fitting
      Debye functions to the structure factors, it is shown that there is good
      agreement between the molar mass of the components obtained from SANS and from
      chromatography. The extraction method also enables, for the first time,
      interchain scattering functions to be produced for scattering between chains of
      different lengths. [Formula: see text].

PMID- 25866455
TI  - Reexamination of the Direct Electrochemical Reduction of S-Nitrosothiols.
AB  - We report here on the electrochemical reduction of S-nitrosothiol species (RSNO).
      Nitric oxide (NO) is the reported common product from electrochemically reduced
      RSNOs at physiological pH. However, studies here at pH 7.4 show that during the
      reduction of RSNOs (-0.6 V to -0.9 V, vs. Ag/AgCl), no significant amount of NO
      is detected. Gas analysis suggests RSNO are reduced to nitrous oxide (N2O) at pH
      7.4 and can only be converted back to NO at more oxidizing voltages.
      Interestingly, at pH 4.0, a direct one-electron reduction of RSNOs appears to
      occur and generates significant amounts of NO from RSNO species.

PMID- 25866456
TI  - Biological evaluation of synthetic chalcone and flavone derivatives as anti
      inflammatory agents.
AB  - Flavonoids and chalcones are natural plant derived compounds with inherent
      therapeutic value for a range of human pathologies. In this study, a series of 24
      substituted chalcones and flavones were synthesized and subsequently screened for
      anti-inflammatory effects on lipopolysaccharide (1 ug/ml)-activated BV-2
      microglial cells by assessing initial production/release of nitric oxide (NO).
      The data obtained eliminate the majority of compounds as weak or non-effective,
      whereas 2'-hydroxy-3,4,5,3',4'-pentamethoxychalcone (1) and 2'-hydroxy-3,4,5
      trimethoxychalcone (2) were potent, having an IC50 of 1.10 and 2.26 uM,
      respectively; with greater potency than L-N6-(1-iminoethyl)lysine selective iNOS
      inhibitor (IC50 = 3.1 uM) but less than steroidal dexamethasone (IC50 < 200 nM).
      The most potent compound (chalcone 1) attenuated NO parallel to reducing iNOS
      protein expression, events also corresponding to reduction of IL-1alpha, IL-10
      and IL-6 pro-inflammatory cytokines. These findings suggest that the presence of
      electron donating groups OH and OCH3 on both A and B rings of synthetic compounds
      correlate to stronger anti-inflammatory potency.

PMID- 25866457
TI  - Ethnic Identity, Gender, and Adolescent Attitude toward School: Adaptive
      Perspectives in Diverse Settings.
AB  - The relationships between adolescent ethnic identity and attitudes toward school
      and school climate are investigated in a small, multiracial/multiethnic city in
      the Great Lakes region with ethnically diverse adolescents taught by primarily
      White teachers. The mixed methods investigation of 986 eighth through eleventh
      grade students during the 2010-2011 academic year suggests that the relationship
      between ethnic identity and attitude toward school is a complex interaction among
      individual characteristics of ethnicity/race, ethnic identity, gender, and
      ecological context. Quantitative results reveal that White female and Hispanic
      and African American male students exhibit strong ethnic identity that correlates
      positively with school attitude; however, qualitative results indicate very
      different paths in getting to those outcomes. Hispanic students appear to benefit
      from a strong ethnic identity that assists with positive relationships at school,
      while African American male students utilize parental cultural socialization as a
      protective function in school. The results emphasize the implications of positive
      school climates for all students.

PMID- 25866459
TI  - Can Parents Provide Brief Intervention Services to Their Drug-Abusing Teenager?
AB  - The importance of parents as "interventionists" is supported by reviews of the
      treatment literature (e.g., Smit, Verdurmen, Monshouwer, & Smit, 2008; Winters,
      Botzet, Fahnhorst, & Koskey, 2009) as well as the emerging science that home
      based initiatives by parents can contribute to desired health changes in
      adolescents (Fearnow, Chassin, Presson, & Sherman, 1998; Jackson & Dickinson,
      2006). Parental influences on an adolescent can include reducing initiation, as
      well as altering its maintenance if it has started. This paper describes a
      project aimed helping parents to deal with a teenager who has already started to
      use alcohol or other drugs. Home Base is a home-based, parent-led program aimed
      at reversing the trajectory of drug use in an already drug-using adolescent. The
      program's content is organized around motivational enhancement and cognitive
      behavioral techniques. The ongoing study will also be discussed.

PMID- 25866460
TI  - The Copper Balance of Cities: Exploratory Insights into a European and an Asian
      City.
AB  - Material management faces a dual challenge: on the one hand satisfying large and
      increasing demands for goods and on the other hand accommodating wastes and
      emissions in sinks. Hence, the characterization of material flows and stocks is
      relevant for both improving resource efficiency and environmental protection.
      This article focuses on the urban scale, a dimension rarely investigated in past
      metal flow studies. We compare the copper (Cu) metabolism of two cities in
      different economic states, namely, Vienna (Europe) and Taipei (Asia). Substance
      flow analysis is used to calculate urban Cu balances in a comprehensive and
      transparent form. The main difference between Cu in the two cities appears to be
      the stock: Vienna seems close to saturation with 180 kilograms per capita
      (kg/cap) and a growth rate of 2% per year. In contrast, the Taipei stock of 30
      kg/cap grows rapidly by 26% per year. Even though most Cu is recycled in both
      cities, bottom ash from municipal solid waste incineration represents an unused
      Cu potential accounting for 1% to 5% of annual demand. Nonpoint emissions are
      predominant; up to 50% of the loadings into the sewer system are from nonpoint
      sources. The results of this research are instrumental for the design of the Cu
      metabolism in each city. The outcomes serve as a base for identification and
      recovery of recyclables as well as for directing nonrecyclables to appropriate
      sinks, avoiding sensitive environmental pathways. The methodology applied is well
      suited for city benchmarking if sufficient data are available.

PMID- 25866461
TI  - Is Word-Problem Solving a Form of Text Comprehension?
AB  - This study's hypotheses were that (a) word-problem (WP) solving is a form of text
      comprehension that involves language comprehension processes, working memory, and
      reasoning, but (b) WP solving differs from other forms of text comprehension by
      requiring WP-specific language comprehension as well as general language
      comprehension. At the start of the 2nd grade, children (n = 206; on average, 7
      years, 6 months) were assessed on general language comprehension, working memory,
      nonlinguistic reasoning, processing speed (a control variable), and foundational
      skill (arithmetic for WPs; word reading for text comprehension). In spring, they
      were assessed on WP-specific language comprehension, WPs, and text comprehension.
      Path analytic mediation analysis indicated that effects of general language
      comprehension on text comprehension were entirely direct, whereas effects of
      general language comprehension on WPs were partially mediated by WP-specific
      language. By contrast, effects of working memory and reasoning operated in
      parallel ways for both outcomes.

PMID- 25866458
TI  - Prediction of the Fate of Organic Compounds in the Environment From Their
      Molecular Properties: A Review.
AB  - A comprehensive review of quantitative structure-activity relationships (QSAR)
      allowing the prediction of the fate of organic compounds in the environment from
      their molecular properties was done. The considered processes were water
      dissolution, dissociation, volatilization, retention on soils and sediments
      (mainly adsorption and desorption), degradation (biotic and abiotic), and
      absorption by plants. A total of 790 equations involving 686 structural molecular
      descriptors are reported to estimate 90 environmental parameters related to these
      processes. A significant number of equations was found for dissociation process
      (pKa), water dissolution or hydrophobic behavior (especially through the KOW
      parameter), adsorption to soils and biodegradation. A lack of QSAR was observed
      to estimate desorption or potential of transfer to water. Among the 686 molecular
      descriptors, five were found to be dominant in the 790 collected equations and
      the most generic ones: four quantum-chemical descriptors, the energy of the
      highest occupied molecular orbital (EHOMO) and the energy of the lowest
      unoccupied molecular orbital (ELUMO), polarizability (alpha) and dipole moment
      (MU), and one constitutional descriptor, the molecular weight. Keeping in mind
      that the combination of descriptors belonging to different categories
      (constitutional, topological, quantum-chemical) led to improve QSAR performances,
      these descriptors should be considered for the development of new QSAR, for
      further predictions of environmental parameters. This review also allows finding
      of the relevant QSAR equations to predict the fate of a wide diversity of
      compounds in the environment.

PMID- 25866464
TI  - Implementation of the Risk-Need-Responsivity Framework across the Juvenile
      Justice Agencies in Singapore.
AB  - The Risk-Need-Responsivity (RNR) framework is regarded as the forefront of
      offender rehabilitation in guiding youth offender risk assessment and
      interventions. This article discusses the juvenile justice system in Singapore
      and the local research that has been conducted in relation to the RNR framework
      and the associated Youth Level of Service (YLS) measures. It describes a journey
      that saw the implementation of the RNR framework across the juvenile justice
      agencies and highlights the challenges that were faced during the implementation
      process on the ground. Finally, the article concludes by providing future
      directions for the implementation of the RNR framework in Singapore.

PMID- 25866465
TI  - New generation of hydraulic pedotransfer functions for Europe.
AB  - A range of continental-scale soil datasets exists in Europe with different
      spatial representation and based on different principles. We developed
      comprehensive pedotransfer functions (PTFs) for applications principally on
      spatial datasets with continental coverage. The PTF development included the
      prediction of soil water retention at various matric potentials and prediction of
      parameters to characterize soil moisture retention and the hydraulic conductivity
      curve (MRC and HCC) of European soils. We developed PTFs with a hierarchical
      approach, determined by the input requirements. The PTFs were derived by using
      three statistical methods: (i) linear regression where there were quantitative
      input variables, (ii) a regression tree for qualitative, quantitative and mixed
      types of information and (iii) mean statistics of developer-defined soil groups
      (class PTF) when only qualitative input parameters were available. Data of the
      recently established European Hydropedological Data Inventory (EU-HYDI), which
      holds the most comprehensive geographical and thematic coverage of hydro
      pedological data in Europe, were used to train and test the PTFs. The applied
      modelling techniques and the EU-HYDI allowed the development of hydraulic PTFs
      that are more reliable and applicable for a greater variety of input parameters
      than those previously available for Europe. Therefore the new set of PTFs offers
      tailored advanced tools for a wide range of applications in the continent.

PMID- 25866462
TI  - Activation and quenching of the phototransduction cascade in retinal cones as
      inferred from electrophysiology and mathematical modeling.
AB  - PURPOSE: To experimentally identify and quantify factors responsible for the
      lower sensitivity of retinal cones compared to rods. METHODS: Electrical
      responses of frog rods and fish (Carassius) cones to short flashes of light were
      recorded using the suction pipette technique. A fast solution changer was used to
      apply a solution that fixed intracellular Ca2+ concentration at the prestimulus
      level, thereby disabling Ca2+ feedback, to the outer segment (OS). The results
      were analyzed with a specially designed mathematical model of phototransduction.
      The model included all basic processes of activation and quenching of the
      phototransduction cascade but omitted unnecessary mechanistic details of each
      step. RESULTS: Judging from the response versus intensity curves, Carassius cones
      were two to three orders of magnitude less sensitive than frog rods. There was a
      large scatter in sensitivity among individual cones, with red-sensitive cones
      being on average approximately two times less sensitive than green-sensitive
      ones. The scatter was mostly due to different signal amplification, since the
      kinetic parameters of the responses among cones were far less variable than
      sensitivity. We argue that the generally accepted definition of the biochemical
      amplification in phototransduction cannot be used for comparing amplification in
      rods and cones, since it depends on an irrelevant factor, that is, the cell's
      volume. We also show that the routinely used simplified parabolic curve fitting
      to an initial phase of the response leads to a few-fold underestimate of the
      amplification. We suggest a new definition of the amplification that only
      includes molecular parameters of the cascade activation, and show how it can be
      derived from experimental data. We found that the mathematical model with
      unrestrained parameters can yield an excellent fit to experimental responses.
      However, the fits with wildly different sets of parameters can be virtually
      indistinguishable, and therefore cannot provide meaningful data on underlying
      mechanisms. Based on results of Ca2+-clamp experiments, we developed an approach
      to strongly constrain the values of many key parameters that set the time course
      and sensitivity of the photoresponse (such as the dark turnover rate of cGMP,
      rates of turnoffs of the photoactivated visual pigment and phosphodiesterase, and
      kinetics of Ca2+ feedback). We show that applying these constraints to our
      mathematical model enables accurate determination of the biochemical
      amplification in phototransduction. It appeared that, contrary to many
      suggestions, maximum biochemical amplification derived for "best" Carassius cones
      was as high as in frog rods. On the other hand, all turnoff and recovery
      reactions in cones proceeded approximately 10 times faster than in rods.
      CONCLUSIONS: The main cause of the differing sensitivity of rods and cones is
      cones' ability to terminate their photoresponse faster.

PMID- 25866466
TI  - Patient safety and interactive medical devices: Realigning work as imagined and
      work as done.
AB  - Medical devices are essential tools for modern healthcare delivery. However,
      significant issues can arise if medical devices are designed for 'work as
      imagined' when this is misaligned with 'work as done'. This problem can be
      compounded as the details of device design, in terms of usability and the way a
      device supports or changes working practices, often receives limited attention.
      The ways devices are designed and used affect patient safety and quality of care:
      inappropriate design can provoke user error, create system vulnerabilities and
      divert attention from other aspects of patient care. Current regulation involves
      a series of pre-market checks relating to device usability, but this assumes that
      devices are always used under the conditions and for the purposes intended (i.e.
      work as imagined); there are many reasons for devices being used in ways other
      than those assumed at development time. Greater attention needs to be paid to
      learning points in actual use and user experience (i.e. work as done). This needs
      to inform manufacturers' designs, management procurement decisions and local
      decisions about how devices are used in practice to achieve co-adaptation;
      without these, we foster risks and inefficiencies in healthcare.

PMID- 25866467
TI  - Flexible kinship: caring for AIDS orphans in rural Lesotho.
AB  - HIV/AIDS has devastated families in rural Lesotho, leaving many children
      orphaned. Families have adapted to the increase in the number of orphans and HIV
      positive children in ways that provide children with the best possible care.
      Though local ideas about kinship and care are firmly rooted in patrilineal social
      organization, in practice, maternal caregivers, often grandmothers, are
      increasingly caring for orphaned children. Negotiations between affinal kin
      capitalize on flexible kinship practices in order to legitimate new patterns of
      care, which have shifted towards a model that often favours matrilocal practices
      of care in the context of idealized patrilineality.

PMID- 25866468
TI  - Joint modelling of repeated measurements and time-to-event outcomes: flexible
      model specification and exact likelihood inference.
AB  - Random effects or shared parameter models are commonly advocated for the analysis
      of combined repeated measurement and event history data, including dropout from
      longitudinal trials. Their use in practical applications has generally been
      limited by computational cost and complexity, meaning that only simple special
      cases can be fitted by using readily available software. We propose a new
      approach that exploits recent distributional results for the extended skew normal
      family to allow exact likelihood inference for a flexible class of random-effects
      models. The method uses a discretization of the timescale for the time-to-event
      outcome, which is often unavoidable in any case when events correspond to
      dropout. We place no restriction on the times at which repeated measurements are
      made. An analysis of repeated lung function measurements in a cystic fibrosis
      cohort is used to illustrate the method.

PMID- 25866470
TI  - Experimental determination of the steady-state charging probabilities and
      particle size conservation in non-radioactive and radioactive bipolar aerosol
      chargers in the size range of 5-40 nm.
AB  - Three bipolar aerosol chargers, an AC-corona (Electrical Ionizer 1090, MSP
      Corp.), a soft X-ray (Advanced Aerosol Neutralizer 3087, TSI Inc.), and an alpha
      radiation-based 241Am charger (tapcon & analysesysteme), were investigated on
      their charging performance of airborne nanoparticles. The charging probabilities
      for negatively and positively charged particles and the particle size
      conservation were measured in the diameter range of 5-40 nm using sucrose
      nanoparticles. Chargers were operated under various flow conditions in the range
      of 0.6-5.0 liters per minute. For particular experimental conditions, some
      deviations from the chosen theoretical model were found for all chargers. For
      very small particle sizes, the AC-corona charger showed particle losses at low
      flow rates and did not reach steady-state charge equilibrium at high flow rates.
      However, for all chargers, operating conditions were identified where the bipolar
      charge equilibrium was achieved. Practically, excellent particle size
      conservation was found for all three chargers.

PMID- 25866469
TI  - Protein Expression by Human Pulmonary Artery Smooth Muscle Cells Containing a
      BMPR2 Mutation and the Action of ET-1 as Determined by Proteomic Mass
      Spectrometry.
AB  - Pulmonary arterial hypertension (PAH) is a disease characterized by increased
      pulmonary vascular resistance and remodeling. Increase in the population of
      vascular smooth muscle cells is among the key events contributing to the
      remodeling. Endothelin-1 (ET-1), a potent vasoconstrictor, is linked to the
      etiology and progression of PAH. Here we analyze changes in protein expressions
      in response to ET-1 in pulmonary arterial smooth muscle cells (PASMC) from a
      healthy Control (non-PAH) and a PAH subject presenting a bone morphogenetic
      protein type II receptor (BMPR2) mutation with exon 1-8 deletion. Protein
      expressions were analyzed by proteomic mass spectrometry using label-free
      quantitation and the correlations were subjected to IngenuityTM Pathway Analysis.
      The results point to eIF2/mTOR/p70S6K, RhoA/actin cytoskeleton/integrin and
      protein unbiquitination as canonical pathways whose protein expressions increase
      with the development of PAH. These pathways have an intimal function in the PAH
      related physiology of smooth muscle proliferation, apoptosis, contraction and
      cellular stress. Exposure of the cells to ET-1 further increases protein
      expression within these pathways. Thus our results show changes in signaling
      pathways as a consequence of PAH and the effect of ET-1 interference on Control
      and PAH-affected cells.

PMID- 25866471
TI  - Ion-Size-Dependent Formation of Mixed Titanium/Lanthanide Oxo Clusters.
AB  - The mixed-metal oxo clusters LnTi4O3(OiPr)2(OMc)11 (Ln = La, Ce; OMc =
      methacrylate), Ln2Ti6O6(OMc)18(HOiPr) (Ln = La, Ce, Nd, Sm) and
      Ln2Ti4O4(OMc)14(HOMc)2 (Ln = Sm, Eu, Gd, Ho) have been synthesized from titanium
      isopropoxide, the corresponding lanthanide acetate and methacrylic acid. The type
      of cluster obtained strongly depends on the size of the lanthanide ion.

PMID- 25866472
TI  - Naturalness in low-scale SUSY models and "non-linear" MSSM.
AB  - In MSSM models with various boundary conditions for the soft breaking terms
      ([Formula: see text]) and for a Higgs mass of 126 GeV, there is a (minimal)
      electroweak fine-tuning [Formula: see text] to [Formula: see text] for the
      constrained MSSM and [Formula: see text] for non-universal gaugino masses. These
      values, often regarded as unacceptably large, may indicate a problem of
      supersymmetry (SUSY) breaking, rather than of SUSY itself. A minimal modification
      of these models is to lower the SUSY breaking scale in the hidden sector
      ([Formula: see text]) to few TeV, which we show to restore naturalness to more
      acceptable levels [Formula: see text] for the most conservative case of low
      [Formula: see text] and ultraviolet boundary conditions as in the constrained
      MSSM. This is done without introducing additional fields in the visible sector,
      unlike other models that attempt to reduce [Formula: see text]. In the present
      case [Formula: see text] is reduced due to additional (effective) quartic Higgs
      couplings proportional to the ratio [Formula: see text] of the visible to the
      hidden sector SUSY breaking scales. These couplings are generated by the
      auxiliary component of the goldstino superfield. The model is discussed in the
      limit its sgoldstino component is integrated out so this superfield is realized
      non-linearly (hence the name of the model) while the other MSSM superfields are
      in their linear realization. By increasing the hidden sector scale [Formula: see
      text] one obtains a continuous transition for fine-tuning values, from this model
      to the usual (gravity mediated) MSSM-like models.

PMID- 25866473
TI  - Performance-based measures of physical function as mortality predictors:
      Incremental value beyond self-reports.
AB  - BACKGROUND: Although previous studies have indicated that performance assessments
      strongly predict future survival, few have evaluated the incremental value in the
      presence of controls for self-reported activity and mobility limitations.
      OBJECTIVE: We assess and compare the added value of four tests - walking speed,
      chair stands, grip strength, and peak expiratory flow (PEF) - for predicting all
      cause mortality. METHODS: Using population-based samples of older adults in Costa
      Rica (n = 2290, aged 60+) and Taiwan (n = 1219, aged 53+), we estimate
      proportional hazards models of mortality for an approximate five-year period.
      Receiver Operator Characteristic (ROC) curves are used to assess the prognostic
      value of each performance assessment. RESULTS: Self-reported measures of physical
      limitations contribute substantial gains in mortality prediction, whereas
      performance-based assessments yield modest incremental gains. PEF provides the
      greatest added value, followed by grip strength. Our results suggest that
      including more than two performance assessments may provide little improvement in
      mortality prediction. CONCLUSIONS: PEF and grip strength are often simpler to
      administer in home interview settings, impose less of a burden on some
      respondents, and, in the presence of self-reported limitations, appear to be
      better predictors of mortality than do walking speed or chair stands. COMMENTS:
      Being unable to perform the test is often a strong predictor of mortality, but
      these indicators are not well-defined. Exclusion rates vary by the specific task
      and are likely to depend on the underlying demographic, health, social and
      cultural characteristics of the sample.

PMID- 25866474
TI  - 'Without Occupation You Don't Exist': Occupational Engagement and Mental Illness.
AB  - This phenomenological study explores the meanings of work for people living with
      severe and enduring mental health conditions. The participants were three women
      and seven men who were attending a mental health day centre. Data were collected
      through up to three depth interviews with each participant over 18 months. The
      interviews were digitally recorded, transcribed verbatim, and analysed according
      to phenomenological principles. Two overarching themes were identified. Building
      and maintaining an occupational identity expressed the ways in which participants
      used occupations as the building blocks of an evolving identity. Most of the
      participants wanted to work, and participation in occupations was seen as
      essential to recovery from mental ill-health. Work and other ways of belonging
      encapsulated the need to feel connected to others. Many of the participants
      envisaged working as a way of achieving this. The longitudinal nature of the
      study facilitated engagement with the developing narratives and exploration of
      the changes and consistencies in the participants' meaning making about their
      occupations. Implications for understanding individuals' occupational
      participation which enhances a sense of self and promotes feelings of belonging
      are identified.

PMID- 25866475
TI  - Reappraisal of the glycerol test in patients with suspected Meniere's disease.
AB  - BACKGROUND: Recent advances in magnetic resonance imaging make it possible to
      visualize the presumed pathophysiologic correlate of Meniere's disease:
      endolymphatic hydrops. As traditional diagnostic tests can provide only indirect
      evidence, they are hardly competitive in this respect and need to be rethought.
      This is done here for the glycerol test. METHODS: The data of a previous
      retrospective analysis of the glycerol test in patients with suspected Meniere's
      disease are reinterpreted using a simple model. The mean threshold reduction
      (MTR) in the frequency range from 125 to 1500 Hz (calculated from audiograms
      obtained immediately before and four hours after the glycerol intake) is used as
      the test statistic. The proposed model explains the frequency distribution of the
      observed MTR by the convolution of a Gaussian probability density function
      (representing measurement errors) with a template representing the frequency
      distribution of the true MTR. The latter is defined in terms of two adjustable
      parameters. After fitting the model to the data, the performance of the test is
      evaluated using receiver operating characteristic (ROC) analysis. RESULTS: The
      cumulative frequency distribution of the observed MTR can be explained almost
      perfectly by the model. According to the ROC analysis performed, the capability
      of the currently used audiometric procedure to detect a glycerol-induced
      threshold reduction corresponds to a diagnostic test of rather high accuracy
      (area under the ROC curve greater than 0.9). Simulations show that methodological
      improvements could further enhance the performance. CONCLUSIONS: Owing to their
      ability to reveal functional aspects without an obvious morphological correlate,
      traditional test for Meniere's disease could be decisive for defining the stage
      of the disease. A distinctive feature of the glycerol test is that it is capable
      of determining, with high accuracy, whether the pathophysiologic condition of the
      inner ear is partially reversible. Prospectively, this could help to estimate the
      chances of specific therapies.

PMID- 25866476
TI  - Experiences of undergoing cardiac surgery among older people diagnosed with
      postoperative delirium: one year follow-up.
AB  - BACKGROUND: Cardiovascular disease is common among old people and many undergo
      cardiac surgery. Scientific knowledge is available on cardiac surgery from
      several perspectives. However, we found few studies focusing on older patients'
      experiences of cardiac surgery. The aim of this study was to illuminate
      experiences of undergoing cardiac surgery among older people diagnosed with
      postoperative delirium, a one year follow-up. METHODS: Qualitative interviews
      were conducted with 49 participants (aged >=70 years) diagnosed with delirium
      after cardiac surgery. Data were collected in Sweden during 2010 through
      individual, semi-structured interviews in participants' homes one year after
      surgery. The interviews were analyzed using qualitative content analysis.
      RESULTS: Four themes with sub-themes were formulated: Feeling drained of
      viability includes having a body under attack, losing strength and being close to
      death. Feeling trapped in a weird world describes participants having
      hallucinations, being in a nightmare and being remorseful for their behavior.
      Being met with disrespect includes feeling disappointed, being forced, and
      feeling like cargo. On the other hand, Feeling safe, including being in
      supportive hands and feeling grateful, points to participants' experiences of
      good care and the gift of getting a second chance in life. CONCLUSIONS: Even one
      year after cardiac surgery, participants described in detail feelings of extreme
      vulnerability and frailty. They also had felt completely in the hands of the
      health care professionals. Participants described experiences of hallucinations
      and nightmares during hospitalization. Cardiac surgery was a unique, fearful,
      traumatic and unpleasant experience yet could also include pleasant or rewarding
      aspects. It seems that health care professionals need deeper knowledge on
      postoperative delirium in order to prevent, detect and treat delirium to avoid
      and relieve the suffering these experiences might cause.

PMID- 25866477
TI  - The effect of epiregulin on epidermal growth factor receptor expression and
      proliferation of oral squamous cell carcinoma cell lines.
AB  - BACKGROUND: Epiregulin (EPR) is a novel member of the epidermal growth factor
      (EGF) family. It has been shown to promote wound healing in oral epithelium,
      enhance proliferation of other epithelial tissues, and is involved in several
      epithelial-related malignancies such as colorectal, lung, and bladder carcinoma.
      More recently, EPR transcripts were found to be high in a study on archival oral
      squamous cell carcinoma (OSCC) specimens. This implies that EPR may be
      responsible for the progression of OSCC. The aim of this was to elucidate the
      effects of EPR on (i) cell morphological changes, (ii) cell proliferation and
      (iii) receptor expression of the H-series OSCC cell lines. METHODS: The
      clinicopathological origin and the expression of the epidermal growth factor
      receptor (EGFR) and ErbB4 receptors of the H-series cell lines were initially
      characterised. Based on these parameters, two of the H-series cell lines, namely
      H103 and H357 were selected for downstream experiments. The cell lines were
      treated with 1 ng/ml, 10 ng/ml, and 20 ng/ml of EPR for 24 and 48 hours in all
      subsequent experiments. Untreated cells acted as the control which was used for
      comparison with each treated group. The cell morphological changes, cell
      proliferation and receptor expression of the OSCC cell lines were evaluated using
      phase contrast microscopy, 5-bromo-2'-deoxy-uridine (BrdU) assays and flow
      cytometry respectively. The results were compared and analysed using the student
      t-test. RESULTS: There were no appreciable morphological changes in the cells
      regardless of the dose of EPR tested nor between the different timelines. There
      were no significant changes in cell proliferation after EPR treatment. As for the
      effect of EPR on receptor expression, 20 ng/ml of EPR significantly reduced the
      density of EGFR expression (p value = 0.049) in the H103 cell line after the 24
      hour treatment. No other statistically significant changes were detected.
      CONCLUSIONS: The results show that EPR had no effect on the morphology and
      proliferativity of OSCC cells. However, the significant decline in EGFR
      expression after EPR treatment suggests that EPR might play an important role in
      the regulation of EGFR expression and hence OSCC progression.

PMID- 25866478
TI  - Curcumin inhibits leptin gene expression and secretion in breast cancer cells by
      estrogen receptors.
AB  - BACKGROUND: Recent studies suggested that leptin as a mitogenic factor might play
      an important role in the process of initiation and progression of human cancer.
      Therefore, it could be considered as a target for breast cancer therapy. A
      previous study has showed that expression of leptin gene could be modulated by
      activation of estrogen receptors. Curcumin is a diferuloylmethane that has been
      shown to interfere with multiple cell signaling pathways and extensive research
      over the last 50 years has indicated this polyphenol can both prevent and treat
      cancer. Based on the fact that targeting of leptin could be considered as a novel
      strategy for breast cancer therapy, the aim of this study is the investigation of
      potentiality of curcumin for inhibition of leptin gene expression and secretion,
      and also, its link with expression of estrogen receptors. METHODS: Cytotoxic
      effect of curcumin on T47D breast cancer cells was investigated by MTT assay test
      after 24 and 48 treatments. Thereafter, the cells treated with different
      concentrations of curcumin. The levels of leptin, estrogen receptor alpha and
      estrogen receptor beta genes expression was measured in the treated and control
      cells by Reverse-transcription real-time PCR. Amount of secreted leptin in the
      culture medium was also determined by ELISA in both treated and untreated cells.
      Finally data were statistically analyzed by one-way ANOVA test. RESULTS: Analysis
      of MTT assay data showed that curcumin inhibits growth of T47D cells with dose
      dependent manner. There were also significant difference between control and
      treated cells in the levels of leptin, estrogen receptor alpha expression levels
      and the quantity of secreted leptin that both were decreased in the treated cells
      compared with control cells. CONCLUSION: Based on the results, curcumin inhibits
      the expression and secretion of leptin and it could probably be used as a drug
      candidate for the breast cancer therapy through the leptin targeting in the
      future.

PMID- 25866479
TI  - Synergistic effects of isomorellin and forbesione with doxorubicin on apoptosis
      induction in human cholangiocarcinoma cell lines.
AB  - BACKGROUND: Chemotherapy for advanced cholangiocarcinoma (CCA) is largely
      ineffective, but innovative combinations of chemotherapeutic agents and natural
      compounds represent a promising strategy. In our previous studies, isomorellin
      and forbesione, caged xanthones isolated from Garcinia hanburyi, were found to
      induce cell cycle arrest and apoptosis in CCA cell lines. The subject of our
      inquiry is the synergistic effect(s) of these caged xanthones with doxorubicin on
      growth inhibition and apoptosis induction in human CCA cell lines. METHODS: KKU
      100, KKU-M139 and KKU-M156 cell lines and Chang cells were treated with either
      isomorellin or forbesione alone or in combination with doxorubicin. Cell
      viability was determined using the sulforhodamine B assay. The combined effects
      of plant compounds with doxorubicin were analyzed using the isobologram and
      combination index method of Chou-Talalay. Apoptosis was determined by ethidium
      bromide/acridine orange staining. Protein expressions were determined by Western
      blot analysis. RESULTS: Isomorellin or forbesione alone inhibited the growth of
      these CCA cell lines in a dose-dependent manner and showed selective cytotoxicity
      against CCA cells but not against Chang cells. Isomorellin/doxorubicin
      combination showed a synergistic growth inhibitory effect on KKU-M139 and KKU
      M156 cells, while the forbesione/doxorubicin combination showed a synergistic
      growth inhibitory effect on KKU-100 and KKU-M139 cells. The percentages of
      apoptotic cells were significantly higher in the combined treatments than in the
      respective single drug treatments. The combined treatments strongly enhanced the
      expression of Bax/Bcl-2, activated caspase-9 and caspase-3, while suppressing the
      expression of survivin, procaspase-9 and procaspase-3, compared with single drug
      treatments. The degree of suppression of NF-kappaB activation mediated by a
      decrease in the expression of NF-kappaB/p65, a reduction of the pIkappaB-alpha
      level and an increase in the IkappaB-alpha protein level, was significantly
      higher in the combined treatment groups than in the single drug treatment groups.
      The degree of suppression of MRP1 protein expression was also significantly
      higher in the combined treatment than in the single drug treatment groups.
      CONCLUSION: The combinations of isomorellin/doxorubicin and
      forbesione/doxorubicin showed significant synergistic effects on the growth
      inhibition and apoptosis induction in KKU-M156 and KKU-100 cells. Caged xanthones
      may be useful adjunct treatments with chemotherapy for Opisthorchis viverrini
      (OV)-associated CCA.

PMID- 25866480
TI  - BCYRN1, a c-MYC-activated long non-coding RNA, regulates cell metastasis of non
      small-cell lung cancer.
AB  - BACKGROUND: Long non-coding RNAs (lncRNAs) are increasingly implicated in the
      regulation of the progression of malignancy. AIM: To clarify the relations among
      BCYRN1 (brain cytoplasmic RNA 1, a long non-coding RNA), c-MYC and cell
      metastasis of non-small-cell lung cancer (NSCLC). METHODS: Real-time PCR was used
      to measure expression of BCYRN1 in NSCLC. Knockdown and overexpression of c-MYC
      were respectively performed using shRNA and lentivirus to investigate its effect
      on BCYRN1 expression. BCYRN1 was respectively knockdown and overexpressed by
      siRNA and BCYRN1 mimics to investigate its role in regulating cell metastasis in
      vitro. ChIP (chromatin immunoprecipitation) assay was performed to confirm the
      binding of c-MYC to the promoter of BCYRN1. Expression levels of matrix
      metalloproteinases (MMP9 and MMP13) were determined using real-time PCR and
      Western blotting. RESULTS: BCYRN1 is upregulated and targeted by c-MYC in NSCLC,
      leading to the increase of cell motility and invasiveness. RNA interference and
      lentivirus infection showed a positive correlation between the expressions of c
      MYC and BCYRN1. ChIP assay confirmed the binding of c-MYC to the promoter region
      of BCYRN1 gene. In-vitro cell metastasis experiments demonstrated that BCYRN1 was
      necessary in the c-MYC-regulated cell migration and invasion. The mRNA and
      protein expression levels of MMP9 and MMP13 descended with the decreasing BCYRN1
      level and ascended with the upregulation of BCYRN1. CONCLUSION: These findings
      uncover a regulatory mechanism in NSCLC cells involving the metastasis-promoting
      lncRNA BCYRN1 that improves expressions of the key metastasis-supporting proteins
      MMP9 and MMP13.

PMID- 25866481
TI  - Association of serum TNF-alpha, IL-8 and free light chain with HLA-DR B alleles
      expression in pulmonary and extra-pulmonary sarcoidosis.
AB  - BACKGROUND: Sarcoidosis is a systemic disease of unknown etiology characterized
      histologically by the observation of non-caseating granulomas and several
      immunological abnormalities. Sarcoidosis is a multi-organ disorder which involves
      formation of granulomas in many tissues including the lungs (pulmonary) and
      others such as skin, bone, heart (extra pulmonary). Associations between human
      leukocyte antigens (HLA), the encoded cell surface receptor (HLA-DR) and
      sarcoidosis have been reported in several studies. Several HLA-DR alleles have
      been described as potential risk factors for sarcoidosis in distinct ethnic
      groups however evidence for a relationship between HLA-DR alleles and pulmonary
      and extra-pulmonary sarcoidosis (EPS) is still scarce. Although the etiology of
      the disease remains unclear, infectious and environmental factors have been
      postulated. Inflammatory cytokines and chemokines may play important roles in the
      pathogenesis of sarcoidosis and serum free light chain (FLC) numbers have been
      implicated in several immunologic disorders. PURPOSE OF THE STUDY: The aim of the
      present study was to investigate HLA associations with serum cytokines and FLC in
      Iranian patients with pulmonary (n = 86) and EPS (n = 46). RESULTS: We found that
      among the 16 HLA DRB alleles only *7 and *12 were different in sarcoidosis
      patients. The levels of TNF-alpha and IL-8 in pulmonary sarcoidosis patients were
      higher than in EPS (P < 0.05) whereas the levels of FLC subunits in EPS were
      higher than in pulmonary sarcoidosis. CONCLUSION: This data may suggests a link
      between HLA-DRB *12 and sarcoidosis in Iranian population.

PMID- 25866482
TI  - A preliminary quantitative proteomic analysis of glioblastoma pseudoprogression.
AB  - BACKGROUNDS: Pseudoprogression disease (PsPD) is commonly observed during
      glioblastoma (GBM) follow-up after adjuvant therapy. Because it is difficult to
      differentiate PsPD from true early progression of GBM, we have used a
      quantitative proteomics strategy to identify molecular signatures and develop
      predictive markers of PsPD. RESULTS: An initial screening of three PsPD and three
      GBM patients was performed, and from which 530 proteins with significant fold
      changes were identified. By conducting biological functional analysis of these
      proteins, we found evidence that the protein synthesis network and the cellular
      growth and proliferation network were most significantly affected. Moreover, six
      of the proteins (HNRNPK, ELAVL1, CDH2, FBLN1, CALU and FGB) involved in the two
      networks were validated (n = 18) in the same six samples and in twelve additional
      samples using immunohistochemistry methods and the western blot analysis. The
      receiver operating characteristic (ROC) curve analysis in distinguishing PsPD
      patients from GBM patients yielded an area under curve (AUC) value of 0.90 (95%
      confidence interval (CI), 0.662-0.9880) for CDH2 and.0.92 (95% CI, 0.696-0.995)
      for CDH2 combined with ELAVL1. CONCLUSIONS: The results of the present study both
      revealed the biological signatures of PsPD from a proteomics perspective and
      indicated that CDH2 alone or combined with ELAVL1 could be potential biomarkers
      with high accuracy in the diagnosis of PsPD.

PMID- 25866484
TI  - Participant Anonymity in the Internet Age: From Theory to Practice.
AB  - Qualitative researchers attempting to protect the identities of their research
      participants now face a multitude of new challenges due to the wealth of
      information once considered private but now readily accessible online. We will
      draw on our research with family members of people with severe brain injury to
      discuss these challenges in relation to three areas: participant engagement with
      the mass media, the availability of court transcripts online, and participants'
      use of social media. We suggest strategies for managing these challenges via
      disguise, refining informed consent, and discussion with interviewees. In the
      context of a largely theoretical literature on anonymization, this article offers
      concrete examples of the dilemmas we faced and will be of illustrative use to
      other researchers confronting similar challenges.

PMID- 25866483
TI  - Thrombosis in inflammatory bowel diseases: what's the link?
AB  - Inflammatory bowel disease affects more than 2 million people in Europe, with
      almost 20% of patients being diagnosed in pediatric age. Patients with
      inflammatory bowel disease are at increased risk of thromboembolic complications
      which may affect patients' morbidity and mortality. The risk of the most common
      thromboembolic events, such as deep venous thrombosis and pulmonary embolism, are
      estimated to be three-fold increased compared to controls, but many other
      districts can be affected. Moreover, patients with ulcerative colitis and Crohn's
      disease experience thromboembolic events at a younger age compared to general
      population. Many factors have been investigated as determinants of the pro
      thrombotic tendency such as acquired risk factors or genetic and immune
      abnormalities, but a unique cause has not been found. Many efforts have been
      focused on the study of abnormalities in the coagulation cascade, its natural
      inhibitors and the fibrinolytic system components and both quantitative and
      qualitative alterations have been demonstrated. Recently the role of platelets
      and microvascular endothelium has been reviewed, as the possible link between the
      inflammatory and hemostatic process. 

PMID- 25866485
TI  - The diversity of fungal genome.
AB  - The genome size of an organism varies from species to species. The C-value
      paradox enigma is a very complex puzzle with regards to vast diversity in genome
      sizes in eukaryotes. Here we reported the detailed genomic information of 172
      fungal species among different fungal genomes and found that fungal genomes are
      very diverse in nature. In fungi, the diversity of genomes varies from 8.97 Mb to
      177.57 Mb. The average genome sizes of Ascomycota and Basidiomycota fungi are
      36.91 and 46.48 Mb respectively. But higher genome size is observed in Oomycota
      (74.85 Mb) species, a lineage of fungus-like eukaryotic microorganisms. The
      average coding genes of Oomycota species are almost doubled than that of
      Acomycota and Basidiomycota fungus. 

PMID- 25866486
TI  - Examining Masculine Norms and Peer Support within a Sample of Incarcerated
      African American Males.
AB  - The adherence to masculine norms has been suggested to be influenced by social
      settings and context. Prisons have been described as a context where survival is
      dependent on adhering to strict masculine norms that may undermine reintegration
      back into the larger society. This study attempted to examine the relationship
      between masculine norms, peer support, and an individual's length of
      incarceration on a sample of 139 African American men taking part in a pre
      release community re-entry program. Results indicate that peer support was
      associated with length of incarceration and the interaction between the
      endorsement of masculine norms and peer support significantly predicted the
      length of incarceration for African American men in this sample. Implications for
      incarcerated African American men and future research directions are discussed.

PMID- 25866487
TI  - Hirshfeld Surface Investigation of Structure-Directing Interactions within
      Dipicolinic Acid Derivatives.
AB  - Six compounds based on dipicolinic acid esters have been synthesized and
      Hirshfeld surfaces used to investigate the structure-directing effects of
      functional groups in controlling their solid-state behavior. Compounds 1-4 are 4
      bromo dipicolinic acid esters substituted with methyl, ethyl, propyl, and benzyl
      groups, respectively. The main structure-directing motif within 1-3 is a pairwise
      O...H interaction involving two carbonyl oxygen atoms and two aromatic H atoms.
      The introduction of bulky benzyl groups in 4 forces a significant change in the
      position of this interaction. Compounds 2 and 4 were used in Suzuki coupling
      reactions to prepare extended analogues 5 and 6, respectively, and their solid
      state behavior was also studied using Hirshfeld surfaces. Extension of these
      dipicolinic acid esters results in the complete loss of the pairwise O...H
      interaction in 5, where the dominant structure-directing motifs are pi-based
      interactions. However, the pairwise O...H interaction reappears for the more
      flexible 6, demonstrating control of the solid-state structure of these
      dipicolinic acid derivatives through the choice of functional groups.

PMID- 25866488
TI  - Tailored Calendar Journals to Ascertain Falls Among Older Adults.
AB  - Although falls are a serious health risk for community-dwelling older adults,
      their ascertainment has been complicated by issues such as recall and reporting
      biases. We examined a novel method, individualized tailored calendars, to
      accurately ascertain falls in older adults. A convenience sample of 125
      cognitively normal participants enrolled in longitudinal studies of healthy aging
      at the Knight Alzheimer's Disease Ressearch Center was followed prospectively for
      12 months. Tailored calendar journal pages were used to document falls daily and
      returned by mail monthly. Participants received a US$5 gift card incentive for
      each month returned. Participants returned 1,487 of 1,500 calendar months over
      the 12-month follow-up for 99.1% compliance rate. There were 154 falls reported.
      Tailored calendar journals and incentives may be effective in ascertaining falls
      among community-dwelling older adults. This tool could improve the accuracy of
      outcome measures for occupational therapy interventions.

PMID- 25866489
TI  - Social Support for Chamorro Breast Cancer Survivors on Guam.
AB  - PURPOSE: The purpose of this study was to assess the types of social support used
      by Chamorro (indigenous) breast cancer survivors on Guam. METHODS: We assessed
      social support use among 25 self-reported Chamorro women with a diagnosis of
      breast cancer through interviews and construction of genograms and ecomaps 
      pictorial displays of the women's family relationships, medical history, and
      their social networks. RESULTS: The mean age of the participants was 54.5 years.
      The average number of years since the diagnosis of breast cancer was 7.8 years.
      Respondents indicated that the nuclear family was the most important form of
      social support (34.2%). Indeed, nuclear family and other types of informal
      systems were the most common type of social support used by the women (60.2%).
      Formal support services, clubs, and organizations were reported by 17.9% of
      participants while spiritual and/or religious resources were reported by 21.9% of
      them. CONCLUSION: These Chamorro breast cancer survivors depended largely on
      family for social support. Support from family, although informal, should be
      recognized as a pivotal factor in recovery and survivorship. Future directions
      could incorporate formal and informal mechanisms to utilize this natural support
      resource.

PMID- 25866491
TI  - Combined covalent-electrostatic model of hydrogen bonding improves structure
      prediction with Rosetta.
AB  - Interactions between polar atoms are challenging to model because at very short
      ranges they form hydrogen bonds (H-bonds) that are partially covalent in
      character and exhibit strong orientation preferences; at longer ranges the
      orientation preferences are lost, but significant electrostatic interactions
      between charged and partially charged atoms remain. To simultaneously model these
      two types of behavior, we refined an orientation dependent model of hydrogen
      bonds [Kortemme et al. J. Mol. Biol. 2003, 326, 1239] used by the molecular
      modeling program Rosetta and then combined it with a distance-dependent Coulomb
      model of electrostatics. The functional form of the H-bond potential is
      physically motivated and parameters are fit so that H-bond geometries that
      Rosetta generates closely resemble H-bond geometries in high-resolution crystal
      structures. The combined potentials improve performance in a variety of
      scientific benchmarks including decoy discrimination, side chain prediction, and
      native sequence recovery in protein design simulations and establishes a new
      standard energy function for Rosetta.

PMID- 25866490
TI  - Genetic profiling of autoinflammatory disorders in patients with periodic fever:
      a prospective study.
AB  - BACKGROUND: Periodic fever syndromes (PFS) are an emerging group of
      autoinflammatory disorders. Clinical overlap exists and multiple genetic analyses
      may be needed to assist diagnosis. We evaluated the diagnostic value of a 5-gene
      sequencing panel (5GP) in patients with undiagnosed PFS. METHODS: Simultaneous
      double strand Sanger sequencing of MEFV, MVK, TNFRSF1A, NLRP3, NLRP12 genes was
      performed in 42 patients with unexplained PFS. Clinical features were correlated
      with genetic results. RESULTS: None of 42 patients analyzed displayed a causative
      genotype. However, single or multiple genetic variants of uncertain significance
      were detected in 24 subjects. Only in 5 subjects a definite diagnosis was made by
      taking into account both genetic and clinical data (2 TRAPS syndrome; 2 FMF; 1
      FCAS). Statistical analysis showed that patients carrying genetic variants in one
      or more of the five selected genes displayed a significantly lower response to
      glucocorticoids compared with subjects who had completely negative genetic
      results. CONCLUSIONS: The sequencing of multiple genes is of little help in the
      diagnostics of PFS and can often lead to results of uncertain interpretation,
      thus the clinically driven sequencing of single genes should remain the
      recommended approach. However, the presence of single or multiple genetic
      variants of uncertain significance, even if not allowing any specific diagnosis,
      correlated with a poorer response to glucocorticoids, possibly indicating a
      multifactorial subgroup of PFS with differential response to pharmacological
      treatment.

PMID- 25866492
TI  - Resilient Practices in Maintaining Safety of Health Information Technologies.
AB  - Electronic health record systems (EHRs) can improve safety and reliability of
      health care, but they can also introduce new vulnerabilities by failing to
      accommodate changes within a dynamic EHR-enabled health care system. Continuous
      assessment and improvement is thus essential for achieving resilience in EHR
      enabled health care systems. Given the rapid adoption of EHRs by many
      organizations that are still early in their experiences with EHR safety, it is
      important to understand practices for maintaining resilience used by
      organizations with a track record of success in EHR use. We conducted interviews
      about safety practices with 56 key informants (including information technology
      managers, chief medical information officers, physicians, and patient safety
      officers) at two large health care systems recognized as leaders in EHR use. We
      identified 156 references to resilience-related practices from 41 informants.
      Framework analysis generated five categories of resilient practices: (a)
      sensitivity to dynamics and interdependencies affecting risks, (b) basic
      monitoring and responding practices, (c) management of practices and resources
      for monitoring and responding, (d) sensitivity to risks beyond the horizon, and
      (e) reflecting on risks with the safety and quality control process itself. The
      categories reflect three functions that facilitate resilience: reflection,
      transcending boundaries, and involving sharp-end practitioners in safety
      management.

PMID- 25866493
TI  - Emotion-based impulsivity, smoking expectancies, and nicotine dependence in
      college students.
AB  - The aim of this study was to enhance our understanding of the relationship
      between affect-related dispositions to rash action, negative urgency (NU: the
      tendency to act rashly when in a negative mood), positive urgency (PU: the
      tendency to act rashly when in a positive mood) and level of nicotine dependence
      symptoms by examining how the two traits transact with affect-related smoking
      expectancies. Based on the Acquired Preparedness model of addictive behaviors, we
      hypothesized that the relationship between PU and level of nicotine dependence
      would be mediated by positive affect smoking expectancies. We also hypothesized
      that the relationship between NU and level of nicotine dependence would be
      mediated by negative affect reduction expectancies. We studied 139 college-aged
      smokers and found support for this model; positive affect expectancies for
      smoking mediated the relationship between PU and level of nicotine dependence
      symptoms. Negative affect reduction smoking expectancies mediated the
      relationship between NU and level of nicotine dependence. The clinical
      implications of this research suggest that prevention/intervention programs
      should include substance-free activities as reinforcement and as ways to deal
      with extreme positive and negative mood.

PMID- 25866494
TI  - Pretesting Qualitative Data Collection Procedures to Facilitate Methodological
      Adherence and Team Building in Nigeria.
AB  - Qualitative methods are becoming widely used and increasingly accepted in
      biomedical research involving teams formed by experts from developing and
      developed practice environments. Resources are rare in offering guidance on how
      to surmount challenges of team integration and resolution of complicated
      logistical issues in a global setting. In this article we present a critical
      reflection of lessons learned and necessary steps taken to achieve methodological
      coherence and international team synergy. A series of 10 pretest interviews were
      conducted to assess instrumentation rigor and formulate measures to address any
      limitations or threats to bias and management procedures before carrying out the
      formal phase of qualitative research, contributing to an evidence-based stroke
      preventive care clinical trial study. The experience of pretesting notably helped
      to identify obstacles and thus increase the methodological and social reliability
      central to conducting credible qualitative research, while also ensuring both
      personal and professional fulfillment of our team members.

PMID- 25866495
TI  - Magnetite Crystal Orientation in Magnetosome Chains.
AB  - One-dimensional magnetic nanostructures have magnetic properties superior to non
      organized materials due to strong uniaxial shape anisotropy. Magnetosome chains
      in magnetotactic bacteria represent a biological paradigm of such magnet, where
      magnetite crystals synthesized in organelles called magnetosomes are arranged
      into linear chains. Two-dimensional synchrotron X-ray diffraction (XRD) is
      applied to cells of magnetotactic bacteria that are pre-aligned with a magnetic
      field to determine the crystallographic orientation of magnetosomes relative to
      the chain axis. The obtained pole figure patterns reveal a [111] fiber texture
      along the chain direction for magnetospirilla strains MSR-1 and AMB-1, whereas a
      [100] fiber texture is measured for Desulfovibrio magneticus strain RS-1. The
      [100] axis appears energetically unfavorable because it represents a magnetic
      hard axis in magnetite, but can be turned into an effective easy axis by particle
      elongation along [100] for aspect ratios higher than 1.25, consistent with aspect
      ratios in RS-1 magnetosomes determined earlier. The pronounced fiber textures can
      be explained either by a strain-specific biological control on crystal
      orientation at the chain level or by physical alignment effects due to intra
      chain magnetic interactions. In this case, biological control of the axis of
      elongation would be sufficient to influence the crystallographic texture of the
      magnetosome chain.

PMID- 25866496
TI  - Polymer/Nanocrystal Hybrid Solar Cells: Influence of Molecular Precursor Design
      on Film Nanomorphology, Charge Generation and Device Performance.
AB  - In this work, molecular tuning of metal xanthate precursors is shown to have a
      marked effect on the heterojunction morphology of hybrid poly(3-hexylthiophene
      2,5-diyl) (P3HT)/CdS blends and, as a result, the photochemical processes and
      overall performance of in situ fabricated hybrid solar cells. A series of cadmium
      xanthate complexes is synthesized for use as in situ precursors to cadmium
      sulfide nanoparticles in hybrid P3HT/CdS solar cells. The formation of CdS
      domains is studied by simultaneous GIWAXS (grazing incidence wide-angle X-ray
      scattering) and GISAXS (grazing incidence small-angle X-ray scattering),
      revealing knowledge about crystal growth and the formation of different
      morphologies observed using TEM (transmission electron microscopy). These
      measurements show that there is a strong relationship between precursor structure
      and heterojunction nanomorphology. A combination of TAS (transient absorption
      spectroscopy) and photovoltaic device performance measurements is used to show
      the intricate balance required between charge photogeneration and percolated
      domains in order to effectively extract charges to maximize device power
      conversion efficiencies. This study presents a strong case for xanthate complexes
      as a useful route to designing optimal heterojunction morphologies for use in the
      emerging field of hybrid organic/inorganic solar cells, due to the fact that the
      nanomorphology can be tuned via careful design of these precursor materials.

PMID- 25866497
TI  - Chinese pediatrician beliefs about counseling and medications for parents who
      smoke: a survey in southern China.
AB  - BACKGROUND: Pediatricians play an important role in promoting smoking cessation
      among the parents of young children as more behavioral counseling and cessation
      treatment are made available in the Chinese healthcare system. However, beliefs
      about the effectiveness of these interventions can influence pediatricians'
      recommendations to their patients. This study examined pediatricians' beliefs
      regarding effectiveness of counseling and medications for smoking cessation.
      METHODS: A cross-sectional survey of pediatricians was conducted in thirteen
      conveniently selected southern Chinese hospitals, during September to December
      2013. A self-administered questionnaire was used for data collection. We used chi
      square tests and multinomial logistic regression analysis to identify factors
      associated with beliefs regarding effectiveness of counseling and medications for
      smoking cessation. RESULTS: Beliefs of the respondents (504/550; 92% response
      rate) were divided regarding the effectiveness of counseling and medications for
      smoking cessation. Sixty percent believed that physician counseling is effective
      for smoking cessation; 53% believed pharmacological products (or medications) are
      effective. Factors that were associated with positive beliefs towards the
      effectiveness of counseling included: believing about the professional
      responsibility to discuss smoking cessation, being confident in discussing
      smoking cessation or SHS exposure reduction with patients' parents, believing
      that health professionals should routinely ask about their patients smoking
      habits, believing that health professionals should routinely advise their smoking
      patients to quit smoking, possessing adequate knowledge in quitting smoking, and
      being able to assess smokers different stages of readiness to quit. Most of the
      above factors were also associated with the belief that medication is effective
      for smoking cessation. CONCLUSIONS: A substantial proportion of Chinese
      pediatricians believed that cessation counseling and medications are not
      effective, which is not supported by current evidence in the field. Several
      factors including individual, practice level and health system level
      characteristics were associated with their belief. Training efforts are needed to
      influence pediatricians' beliefs regarding the effectiveness of cessation
      counseling and medications.

PMID- 25866498
TI  - Dual-thread parallel control strategy for ophthalmic adaptive optics.
AB  - To improve ophthalmic adaptive optics speed and compensate for ocular wavefront
      aberration of high temporal frequency, the adaptive optics wavefront correction
      has been implemented with a control scheme including 2 parallel threads; one is
      dedicated to wavefront detection and the other conducts wavefront reconstruction
      and compensation. With a custom Shack-Hartmann wavefront sensor that measures the
      ocular wave aberration with 193 subapertures across the pupil, adaptive optics
      has achieved a closed loop updating frequency up to 110 Hz, and demonstrated
      robust compensation for ocular wave aberration up to 50 Hz in an adaptive optics
      scanning laser ophthalmoscope.

PMID- 25866499
TI  - High Performance GPU-Based Fourier Volume Rendering.
AB  - Fourier volume rendering (FVR) is a significant visualization technique that has
      been used widely in digital radiography. As a result of its ??(N (2)log?N) time
      complexity, it provides a faster alternative to spatial domain volume rendering
      algorithms that are ??(N (3)) computationally complex. Relying on the Fourier
      projection-slice theorem, this technique operates on the spectral representation
      of a 3D volume instead of processing its spatial representation to generate
      attenuation-only projections that look like X-ray radiographs. Due to the rapid
      evolution of its underlying architecture, the graphics processing unit (GPU)
      became an attractive competent platform that can deliver giant computational raw
      power compared to the central processing unit (CPU) on a per-dollar-basis. The
      introduction of the compute unified device architecture (CUDA) technology enables
      embarrassingly-parallel algorithms to run efficiently on CUDA-capable GPU
      architectures. In this work, a high performance GPU-accelerated implementation of
      the FVR pipeline on CUDA-enabled GPUs is presented. This proposed implementation
      can achieve a speed-up of 117x compared to a single-threaded hybrid
      implementation that uses the CPU and GPU together by taking advantage of
      executing the rendering pipeline entirely on recent GPU architectures. 

PMID- 25866500
TI  - Analysis of human standing balance by largest lyapunov exponent.
AB  - The purpose of this research is to analyse the relationship between nonlinear
      dynamic character and individuals' standing balance by the largest Lyapunov
      exponent, which is regarded as a metric for assessing standing balance. According
      to previous study, the largest Lyapunov exponent from centre of pressure time
      series could not well quantify the human balance ability. In this research, two
      improvements were made. Firstly, an external stimulus was applied to feet in the
      form of continuous horizontal sinusoidal motion by a moving platform. Secondly, a
      multiaccelerometer subsystem was adopted. Twenty healthy volunteers participated
      in this experiment. A new metric, coordinated largest Lyapunov exponent was
      proposed, which reflected the relationship of body segments by integrating
      multidimensional largest Lyapunov exponent values. By using this metric in actual
      standing performance under sinusoidal stimulus, an obvious relationship between
      the new metric and the actual balance ability was found in the majority of the
      subjects. These results show that the sinusoidal stimulus can make human balance
      characteristics more obvious, which is beneficial to assess balance, and balance
      is determined by the ability of coordinating all body segments. 

PMID- 25866501
TI  - Traffic speed data imputation method based on tensor completion.
AB  - Traffic speed data plays a key role in Intelligent Transportation Systems (ITS);
      however, missing traffic data would affect the performance of ITS as well as
      Advanced Traveler Information Systems (ATIS). In this paper, we handle this issue
      by a novel tensor-based imputation approach. Specifically, tensor pattern is
      adopted for modeling traffic speed data and then High accurate Low Rank Tensor
      Completion (HaLRTC), an efficient tensor completion method, is employed to
      estimate the missing traffic speed data. This proposed method is able to recover
      missing entries from given entries, which may be noisy, considering severe
      fluctuation of traffic speed data compared with traffic volume. The proposed
      method is evaluated on Performance Measurement System (PeMS) database, and the
      experimental results show the superiority of the proposed approach over state-of
      the-art baseline approaches. 

PMID- 25866502
TI  - Modelling coupled oscillations in the Notch, Wnt, and FGF signaling pathways
      during somitogenesis: a comprehensive mathematical model.
AB  - Somite formation in the early stage of vertebrate embryonic development is
      controlled by a complicated gene network named segmentation clock, which is
      defined by the periodic expression of genes related to the Notch, Wnt, and the
      fibroblast growth factor (FGF) pathways. Although in recent years some findings
      about crosstalk among the Notch, Wnt, and FGF pathways in somitogenesis have been
      reported, the investigation of their crosstalk mechanisms from a systematic point
      of view is still lacking. In this study, a more comprehensive mathematical model
      was proposed to simulate the dynamics of the Notch, Wnt, and FGF pathways in the
      segmentation clock. Simulations and bifurcation analyses of this model suggested
      that the concentration gradients of both Wnt, and FGF signals along the
      presomitic mesoderm (PSM) are corresponding to the whole process from start to
      stop of the segmentation clock. A number of highly sensitive parameters to the
      segmentation clock's oscillatory pattern were identified. By further bifurcation
      analyses for these sensitive parameters, and several complementary mechanisms in
      respect of the maintenance of the stable oscillation of the segmentation clock
      were revealed. 

PMID- 25866503
TI  - Test statistics for the identification of assembly neurons in parallel spike
      trains.
AB  - In recent years numerous improvements have been made in multiple-electrode
      recordings (i.e., parallel spike-train recordings) and spike sorting to the
      extent that nowadays it is possible to monitor the activity of up to hundreds of
      neurons simultaneously. Due to these improvements it is now potentially possible
      to identify assembly activity (roughly understood as significant synchronous
      spiking of a group of neurons) from these recordings, which-if it can be
      demonstrated reliably-would significantly improve our understanding of neural
      activity and neural coding. However, several methodological problems remain when
      trying to do so and, among them, a principal one is the combinatorial explosion
      that one faces when considering all potential neuronal assemblies, since in
      principle every subset of the recorded neurons constitutes a candidate set for an
      assembly. We present several statistical tests to identify assembly neurons
      (i.e., neurons that participate in a neuronal assembly) from parallel spike
      trains with the aim of reducing the set of neurons to a relevant subset of them
      and this way ease the task of identifying neuronal assemblies in further
      analyses. These tests are an improvement of those introduced in the work by
      Berger et al. (2010) based on additional features like spike weight or pairwise
      overlap and on alternative ways to identify spike coincidences (e.g., by avoiding
      time binning, which tends to lose information). 

PMID- 25866504
TI  - Kernel temporal differences for neural decoding.
AB  - We study the feasibility and capability of the kernel temporal difference
      (KTD)(lambda) algorithm for neural decoding. KTD(lambda) is an online, kernel
      based learning algorithm, which has been introduced to estimate value functions
      in reinforcement learning. This algorithm combines kernel-based representations
      with the temporal difference approach to learning. One of our key observations is
      that by using strictly positive definite kernels, algorithm's convergence can be
      guaranteed for policy evaluation. The algorithm's nonlinear functional
      approximation capabilities are shown in both simulations of policy evaluation and
      neural decoding problems (policy improvement). KTD can handle high-dimensional
      neural states containing spatial-temporal information at a reasonable
      computational complexity allowing real-time applications. When the algorithm
      seeks a proper mapping between a monkey's neural states and desired positions of
      a computer cursor or a robot arm, in both open-loop and closed-loop experiments,
      it can effectively learn the neural state to action mapping. Finally, a
      visualization of the coadaptation process between the decoder and the subject
      shows the algorithm's capabilities in reinforcement learning brain machine
      interfaces. 

PMID- 25866505
TI  - Sentiment analysis using common-sense and context information.
AB  - Sentiment analysis research has been increasing tremendously in recent times due
      to the wide range of business and social applications. Sentiment analysis from
      unstructured natural language text has recently received considerable attention
      from the research community. In this paper, we propose a novel sentiment analysis
      model based on common-sense knowledge extracted from ConceptNet based ontology
      and context information. ConceptNet based ontology is used to determine the
      domain specific concepts which in turn produced the domain specific important
      features. Further, the polarities of the extracted concepts are determined using
      the contextual polarity lexicon which we developed by considering the context
      information of a word. Finally, semantic orientations of domain specific features
      of the review document are aggregated based on the importance of a feature with
      respect to the domain. The importance of the feature is determined by the depth
      of the feature in the ontology. Experimental results show the effectiveness of
      the proposed methods. 

PMID- 25866506
TI  - Probe-based confocal laser endomicroscopy for indeterminate biliary strictures:
      refinement of the image interpretation classification.
AB  - Background. Accurate diagnosis and clinical management of indeterminate biliary
      strictures are often a challenge. Tissue confirmation modalities during
      Endoscopic Retrograde Cholangiopancreatography (ERCP) suffer from low sensitivity
      and poor diagnostic accuracy. Probe-based confocal laser endomicroscopy (pCLE)
      has been shown to be sensitive for malignant strictures characterization (98%)
      but lacks specificity (67%) due to inflammatory conditions inducing false
      positives. Methods. Six pCLE experts validated the Paris Classification, designed
      for diagnosing inflammatory biliary strictures, using a set of 40 pCLE sequences
      obtained during the prospective registry (19 inflammatory, 6 benign, and 15
      malignant). The 4 criteria used included (1) multiple thin white bands, (2) dark
      granular pattern with scales, (3) increased space between scales, and (4)
      thickened reticular structures. Interobserver agreement was further calculated on
      a separate set of 18 pCLE sequences. Results. Overall accuracy was 82.5% (n = 40
      retrospectively diagnosed) versus 81% (n = 89 prospectively collected) for the
      registry, resulting in a sensitivity of 81.2% (versus 98% for the prospective
      study) and a specificity of 83.3% (versus 67% for the prospective study). The
      corresponding interobserver agreement for 18 pCLE clips was fair (k = 0.37).
      Conclusion. Specificity of pCLE using the Paris Classification for the
      characterization of indeterminate bile duct stricture was increased, without
      impacting the overall accuracy. 

PMID- 25866508
TI  - Comparison of GnRH agonist, GnRH antagonist, and GnRH antagonist mild protocol of
      controlled ovarian hyperstimulation in good prognosis patients.
AB  - The reports on how to stimulate the ovaries for oocyte retrieval in good
      prognosis patients are contradictory and often favor one type of controlled
      ovarian hyperstimulation (COH). For this reason, we retrospectively analyzed data
      from IVF/ICSI cycles carried out at our IVF Unit in good prognosis patients (aged
      <38 years, first and second attempts of IVF/ICSI, more than 3 oocytes retrieved)
      to elucidate which type of COH is optimal at our condition. The included patients
      were undergoing COH using GnRH agonist, GnRH antagonist or GnRH antagonist mild
      protocol in combination with gonadotrophins. We found significant differences in
      the average number of retrieved oocytes, immature oocytes, fertilized oocytes,
      embryos, transferred embryos, embryos frozen per cycle, and cycles with embryo
      freezing between studied COH protocols. Although there were no differences in
      live birth rate (LBR), miscarriages, and ectopic pregnancies between compared
      protocols, pregnancy rate was significantly higher in GnRH antagonist mild
      protocol in comparison with both GnRH antagonist and GnRH agonist protocols and
      cumulative LBR per cycle was significantly higher in GnRH antagonist mild
      protocol in comparison to GnRH agonist protocol. Our data show that GnRH
      antagonist mild protocol of COH could be the best method of choice in good
      prognosis patients. 

PMID- 25866507
TI  - Treatment of nonalcoholic steatohepatitis in adults: present and future.
AB  - Nonalcoholic steatohepatitis has become one of the most common liver-related
      health problems. This condition has been linked to an unhealthy diet and weight
      gain, but it can also be observed in nonobese people. The standard of care is
      represented by the lifestyle intervention. However, because this approach has
      several limitations, such as a lack of compliance, the use of many drugs has been
      proposed. The first-line pharmacological choices are vitamin E and pioglitazone,
      both showing a positive effect on transaminases, fat accumulation, and
      inflammation. Nevertheless, vitamin E has no proven effect on fibrosis and on
      long-term morbidity and mortality and pioglitazone has a negative impact on
      weight. Other drugs have been studied such as metformin, ursodeoxycholic acid,
      statins, pentoxiphylline, and orlistat with only partially positive results.
      Among the emerging treatments, telmisartan is particularly interesting as it
      seems to have an impact on insulin resistance, liver steatosis, inflammation, and
      fibrosis. However, the pathogenesis of steatohepatitis is highly complex and is
      determined by different parallel hits; indeed, the association of different drugs
      that act on various levels has been suggested. In conclusion, lifestyle
      intervention should be optimised and the associations of different drugs should
      be tested in large studies with long-term outcomes. 

PMID- 25866509
TI  - Ghrelin Increases Beta-Catenin Level through Protein Kinase A Activation and
      Regulates OPG Expression in Rat Primary Osteoblasts.
AB  - Ghrelin, by binding growth hormone secretagogue receptor (GHS-R), promotes
      osteoblast proliferation but the signaling mechanism of GHS-R on these cells
      remains unclear. Since canonical Wnt/beta-catenin pathway is critically
      associated with bone homeostasis, we investigated its involvement in mediating
      ghrelin effects in osteoblasts and in osteoblast-osteoclast cross talk. Ghrelin
      (10(-10)M) significantly increased beta-catenin levels in rat osteoblasts (rOB).
      This stimulatory action on beta-catenin involves a specific interaction with GHS
      R1a, as it is prevented by the selective GHS-R1a antagonist, D-Lys(3)-GHRP-6 (10(
      7)M). The effect of ghrelin on beta-catenin involves the phosphorylation and
      inactivation of GSK-3beta via protein kinase A (PKA). Inhibition of PKA activity
      reduces the facilitatory action of ghrelin on beta-catenin stabilization. Ghrelin
      treatment of rOB significantly increases the expression of osteoprotegerin (OPG),
      which plays an important role in the regulation of osteoclastogenesis, and this
      effect is blocked by D-Lys(3)-GHRP-6. Furthermore, ghrelin reduced RANKL/OPG
      ratio thus contrasting osteoclastogenesis. Accordingly, conditioned media from
      rOB treated with ghrelin decreased the number of multinucleated TRAcP+ cells as
      compared with the conditioned media from untreated-control rOB. Our data suggest
      new roles for ghrelin in modulating bone homeostasis via a specific interaction
      with GHSR-1a in osteoblasts with subsequent enhancement of both beta-catenin
      levels and OPG expression. 

PMID- 25866510
TI  - Chemosensitivity of anaplastic thyroid cancer based on a histoculture drug
      response assay.
AB  - The chemosensitivity of anaplastic thyroid cancer (ATC) to some cytotoxic agents
      was investigated by the histoculture drug response assay (HDRA). Thirty specimens
      from 22 patients with ATC were obtained from surgically resected subjects. The
      drugs tested were paclitaxel (PTX), docetaxel (DOC), adriamycin (ADM), nedaplatin
      (254-S), cisplatin (CDDP), carboplatin (CBDCA), etoposide (VP-16), 5-fluorouracil
      (5-FU), mitomycin C (MMC), and cyclophosphamide (CPA). PTX was the most effective
      agent, and 25 of 29 cases (86.2%) had high inhibition rates (IRs; over 70%),
      while DOC, another taxane, had lower IRs (median, 32.6%). 254-S had the second
      highest IR (median 68.1%), higher than other platins, CDDP (median 47.3%) and
      CBDCA (median 27.4%). The IR of 50% dose PTX (20 MUg/mL, median 30.6%) was
      markedly decreased, while that of 50% dose 254-S (10 MUg/mL, median 63.3%) still
      retained its inhibition effect compared to 100% dose. Most recurrent samples had
      higher IRs than primary lesions, but the IRs of different drugs differed between
      primary and recurrent lesions, even with samples from the same patients. PTX has
      a higher IR to ATC tissues in the HDRA, which suggests that it may be a key drug
      for the treatment of patients with ATC. 

PMID- 25866511
TI  - Rapid characterization of tanshinone extract powder by near infrared
      spectroscopy.
AB  - Chemical and physical quality attributes of herbal extract powders play an
      important role in the research and development of Chinese medicine preparations.
      The active pharmaceutical ingredients have a direct impact on the herbal
      extract's efficacy, while the physical properties of raw material affect the
      pharmaceutical manufacturing process and the final products' quality. In this
      study, tanshinone extract powders from Salvia miltiorrhiza which are widely used
      for the treatment of cardiovascular diseases in the clinic are taken as the
      research object. Both the chemical information and physical information of
      tanshinone extract powders are analyzed by near infrared (NIR) spectroscopy. The
      partial least squares (PLS) and least square support vector machine (LS-SVM)
      models are investigated to build the relationship between NIR spectra and
      reference values. PLS models performed well for the content of crytotanshinone,
      tanshinone IIA, the moisture, and average median particle size, while, for
      specific surface area and tapped density, the LS-SVM models performed better than
      the PLS models. Results demonstrated NIR to be a valid and fast process
      analytical technology tool to simultaneously determine multiple quality
      attributes of herbal extract powders and indicated that there existed some
      nonlinear relationship between NIR spectra and physical quality attributes. 

PMID- 25866512
TI  - A Case of Scopulariopsis brevicaulis Endocarditis with Mycotic Aneurysm in an
      Immunocompetent Host.
AB  - Scopulariopsis is a genus of mold that is usually associated with onychomycosis
      and rarely causes complicated infection in immunocompetent persons. We describe a
      case of an immunocompetent 65-year-old male with a history of mitral valve repair
      with prosthetic ring placement who developed acute left posterior knee pain.
      Imaging showed a left popliteal artery aneurysm and thrombus, and further
      evaluation with transesophageal echocardiogram demonstrated two large, mobile
      mitral valve vegetations. He underwent debridement and replacement of the mitral
      valve, followed by debridement of the left popliteal artery with peroneal artery
      bypass. The intraoperative cultures grew Scopulariopsis brevicaulis. Due to the
      resistant nature of the organism, he was initially treated with combination
      antifungals including liposomal amphotericin B, caspofungin, and voriconazole and
      was continued on chronic suppression with posaconazole with no evidence of
      recurrence. Scopulariopsis is a rare cause of fungal endocarditis. Treatment of
      Scopulariopsis endocarditis is challenging and is not well understood due to its
      rarity. 

PMID- 25866514
TI  - Vilazodone for the treatment of major depressive disorder: focusing on its
      clinical studies and mechanism of action.
AB  - We tried to review and update clinical and preclinical studies evaluating
      vilazodone's role as an antidepressant for patients with major depressive
      disorder (MDD). In terms of its mechanism of actions, we sought to elaborate them
      mainly through preclinical animal studies. A data search was conducted in
      November 1, 2013, using the key terms "vilazodone" or "Viibryd," in PubMed and
      Medline databases. All published and unpublished studies are included and
      citations from publications were also reviewed for additional references. Five
      unpublished, phase-II and two pivotal published phase-III clinical trials with
      nearly identical design (8-week, double-blind, randomized, and placebo
      controlled) investigated efficacy of vilazodone, were found for the treatment of
      patients with MDD. Two post-hoc studies and one long-term open study were also
      included. Data were thoroughly reviewed to incorporate the pharmacology, action
      mechanism, efficacy and safety for the vilazodone in the treatment of major
      depressive disorder. Vilazodone is an antidepressant with novel mechanism of
      action because its chemical structure is unrelated to conventional
      antidepressant, and it has a selective serotonin (5-HT) reuptake inhibitor and 5
      HT1A receptor partial agonist profile. Vilazodone is an effective and safe
      treatment option with its novel action mechanisms for patients with depression.
      Its putative benefits compared with other antidepressants must be thoroughly
      studied in adequately-powered and well-designed future clinical trials. 

PMID- 25866516
TI  - Childhood exposure to psychological trauma and the risk of suicide attempts: the
      modulating effect of psychiatric disorders.
AB  - OBJECTIVE: We examined whether childhood exposure to psychological trauma is
      associated with greater suicidality and whether specific psychiatric disorders
      modulate this association in a representative sample of Korean adults. METHODS:
      The Korean version of the Composite International Diagnostic Interview 2.1 was
      administered to 6,027 subjects aged 18-74 years. Subjects who experienced a
      traumatic event before the age of 18 years, the childhood-trauma-exposure group,
      were compared with controls without childhood trauma exposure. RESULTS: Childhood
      exposure to psychological trauma was associated with lifetime suicidal ideation
      (OR=3.19, 95% CI=2.42-4.20), suicide plans (OR=4.15, 95% CI=2.68-6.43), and
      suicide attempts (OR=4.52, 95% CI=2.97-6.88). These associations weakened after
      further adjustment for any psychiatric disorders, but they were not eliminated.
      The risk of suicide attempts related to childhood trauma increased with the
      presence of a concurrent alcohol use, depressive, or eating disorder. CONCLUSION:
      In terms of clinical implications, patients with these disorders who have a
      history of childhood trauma should be carefully assessed for their suicide risk
      and aggressively treated for psychiatric disorders.

PMID- 25866515
TI  - Prevalence and Correlates of DSM-IV Mental Disorders in South Korean Adults: The
      Korean Epidemiologic Catchment Area Study 2011.
AB  - OBJECTIVE: The aim of this study was to estimate the prevalence and correlates of
      mental disorders in Korean adults. METHODS: Door to door household surveys were
      conducted with community residents aged 18-74 years from July 19, 2011, to
      November 16, 2011 (n=6,022, response rate 78.7%). The sample was drawn from 12
      catchment areas using a multistage cluster method. Each subject was assessed
      using the Korean version of the World Health Organization Composite International
      Diagnostic Interview (CIDI) based on the Diagnostic and Statistical Manual of
      Mental Disorders, Fourth Edition (DSM-IV). RESULTS: Lifetime and 12-month
      prevalence estimates were as follows: alcohol use disorders, 13.4% and 4.4%,
      respectively; nicotine use disorders, 7.2% and 4.0%, respectively; anxiety
      disorders, 8.7% and 6.8%, respectively; and mood disorders, 7.5% and 3.6%,
      respectively. The prevalence rates of all types of DSM-IV mental disorders were
      27.6% and 16.0%, respectively. Being female; young; divorced, separated, or
      widowed; and in a low-income group were associated with mood and anxiety
      disorders after adjustment for various demographic variables, whereas being male
      and young were associated with alcohol use disorders. Higher income was not
      correlated with alcohol use disorder as it had been in the 2001 survey.
      CONCLUSION: The rate of depressive disorders has increased since 2001 (the first
      national survey), whereas that of anxiety disorders has been relatively stable.
      The prevalence of nicotine and alcohol use disorders has decreased, and the male
      to-female ratio of those with this diagnosis has also decreased.

PMID- 25866513
TI  - Adult vascular wall resident multipotent vascular stem cells, matrix
      metalloproteinases, and arterial aneurysms.
AB  - Evidences have shown the presence of multipotent stem cells (SCs) at sites of
      arterial aneurysms: they can differentiate into smooth muscle cells (SMCs) and
      are activated after residing in a quiescent state in the vascular wall. Recent
      studies have implicated the role of matrix metalloproteinases in the pathogenesis
      of arterial aneurysms: in fact the increased synthesis of MMPs by arterial SMCs
      is thought to be a pivotal mechanism in aneurysm formation. The factors and
      signaling pathways involved in regulating wall resident SC recruitment, survival,
      proliferation, growth factor production, and differentiation may be also related
      to selective expression of different MMPs. This review explores the relationship
      between adult vascular wall resident multipotent vascular SCs, MMPs, and arterial
      aneurysms. 

PMID- 25866517
TI  - Wake up time, light, and mood in a population sample age 40-64 years.
AB  - OBJECTIVE: Concern that disturbances of sleep and light exposures at night might
      increase cancer risks have been expressed, but little actual exposure data has
      been collected. Measurements from a representative population sample were
      examined to understand the magnitude of in-bed light exposure at night and
      possible correlates. METHODS: From 1990 to 1994, a home survey of sleep disorders
      among adults ages 40-64 was conducted in the City of San Diego California, using
      stratified representative sampling techniques. Along with questionnaires, sleep
      logs, and 3-night wrist activity and pulse oximetry measures, bedside
      illumination was measured with a computer recording system. Questionnaires
      included the CESD depression scale and a scale of symptoms typical of winter
      depression. RESULTS: Complete data were available from 286 men and women, whose
      mean in-bed intervals averaged 7 hours and 42 minutes. The mean room illumination
      during the first part of the night was mean 12.7 lux (median 3.2 lux) and during
      the last 2 hours in bed averaged 28.7 lux (median 18.9 lux). Nocturnal light
      exposure was positively correlated with age, male gender, summer season, time in
      bed, wake-up time, and depressive symptoms. CONCLUSION: Complex bi-directional
      interactions may take place between sleep disturbances, depression, time in bed,
      wake-up-time, and in-bed illumination. The most crucial light exposures appear to
      occur in the last 2 hours in bed, largely after dawn, so daylight exposure may be
      an important factor.

PMID- 25866518
TI  - A Comparison of Personality Characteristics and Psychiatric Symptomatology
      between Upper Airway Resistance Syndrome and Obstructive Sleep Apnea Syndrome.
AB  - OBJECTIVE: To investigate the personality characteristics of patients with upper
      airway resistance syndrome (UARS) and those of patients with obstructive sleep
      apnea syndrome (OSAS). METHODS: Eighty-eight patients with UARS and 365 patients
      with OSAS participated. All patients had a diagnostic full-night attended
      polysomnography (PSG) and completed the Athens Insomnia Scale (AIS), Pittsburgh
      Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Symptom Checklist-90
      Revision (SCL-90-R) and Eysenck Personality Questionnaire (EPQ). RESULTS: The
      UARS group scored significantly higher than the OSAS group on the ESS, AIS, and
      PSQI (p<0.001). The scores of all SCL-90-R subscales in the UARS group were
      significantly higher than those in the OSA group (all p<0.001, except for
      somatization, p=0.016). Patients with UARS scored lower on EPQ-E
      (extroversion/introversion) (p=0.006) and EPQ-L (lie) (p<0.001) than those with
      OSA. UARS patients also showed higher scores on EPQ-P (psychoticism) (p=0.002)
      and EPQ-N (neuroticism) (p<0.001) than OSAS patients. CONCLUSION: Our results
      suggest that patients with UARS have worse subjective sleep quality than OSAS
      patients in spite of their better PSG findings. UARS patients tend to have more
      neurotic and sensitive personalities than patients with OSAS, which may be a
      cause of the clinical features of UARS.

PMID- 25866519
TI  - The psychometric properties of the korean version of the verbal abuse
      questionnaire in university students.
AB  - OBJECTIVE: The aim of the present study was to examine the psychometric
      properties of the Korean Verbal Abuse Questionnaire (K-VAQ) that consists of 15
      items related with life-time verbal aggression exposure. METHODS: A total of 5814
      university students who agreed to take part in the study completed the K-VAQ, the
      Korean version of the Life Event CheckList (LEC-K) and Impact of Event Scale
      Revised (K-IES-R). Internal consistency was checked by using item-total item
      correlation and Cronbach's alpha coefficient. Exploratory and confirmatory factor
      analyses were performed, and convergent and concurrent validity levels were
      examined. Finally, a cluster analysis was conducted to verify the validity of the
      cutoff point of the K-VAQ. RESULTS: The Cronbach's alpha correlation coefficient
      was 0.9. The K-VAQ showed a single factor structure which explained 55.34% of the
      total variance. The K-VAQ was significantly associated with the LEC-K (r=0.24)
      and K-IES-R (r=0.28), indicating good convergent validity and concurrent
      validity. The cluster analysis provided four clusters of trauma experiences:
      high, moderate, low, and minimal, with K-VAQ ranges of 43-81, 20-42, 7-19, and 0
      6, respectively. In a further investigation, a K-VAQ score of 40 was found to be
      the appropriate cutoff point to delineate the highly verbally abused group, as
      used in the previous studies. A sum of 36.5% of the highly verbally abused group
      reported to show substantial symptoms of PTSD (K-IES-R score >22). CONCLUSION:
      The present findings suggest that the K-VAQ has good psychometric properties for
      assessing verbal aggression among the Korean population.

PMID- 25866520
TI  - The Relationship between Type D Personality and Heart Rate Variability in
      Community Mental Health Center Users.
AB  - OBJECTIVE: Type D personality can be regarded as a promising cardiovascular risk
      marker that has been repeatedly linked to relevant indicators of mental health,
      quality of life, morbidity, and mortality in cardiac patients. Heart rate
      variability (HRV) is a non-invasive technology that can provide information
      regarding a patient's sympathetic/parasympathetic balance and the control
      mechanisms of the autonomic systems in the cardiovascular system. As both type D
      personality and HRV are parameters related to the cardiovascular system, we
      assumed a relationship between type D personality and HRV. This study set out to
      identify the relationship between type D and HRV and the differences in HRV
      variables between type D and non-type D personalities. METHODS: Patients who
      visited Guro Community Mental Health Center from January 2011 to December 2012
      were surveyed. They were evaluated using both the Korean version of the Type D
      Personality-14 for type D personality and HRV. During the survey, those who
      reported major cardiovascular disease that can affect heart rate variability were
      excluded from the study. RESULTS: Our analysis included 559 participants, 249 of
      whom were classified as type D personality. No significant differences were found
      in the HRV variables between the type D group and the non-type D group. There
      were also no clinically meaningful correlations between HRV variables and type D
      total/subscale scores when controlled for patient age. CONCLUSION: A relationship
      between HRV and type D personality was not identified using short-term HRV
      measurements in non-clinical patients with no definitive cardiovascular disease.
      Further studies using long-term HRV measurements in patients with cardiovascular
      disease are necessary to conclude an association between HRV and type D
      personality.

PMID- 25866521
TI  - Celebrity suicides and their differential influence on suicides in the general
      population: a national population-based study in Korea.
AB  - OBJECTIVE: Although evidence suggests that there is an increase in suicide rates
      in the general population following celebrity suicide, the rates are
      heterogeneous across celebrities and countries. It is unclear which is the more
      vulnerable population according to the effect sizes of celebrity suicides to
      general population. METHODS: All suicide victims in the general population
      verified by the Korea National Statistical Office and suicides of celebrity in
      South Korea were included for 7 years from 2005 to 2011. Effect sizes were
      estimated by comparing rates of suicide in the population one month before and
      after each celebrity suicide. The associations between suicide victims and
      celebrities were examined. RESULTS: Among 94,845 suicide victims, 17,209
      completed suicide within one month after 13 celebrity suicides. Multivariate
      logistic regression analyses revealed that suicide victims who died after
      celebrity suicide were significantly likely to be of age 20-39, female, and to
      die by hanging. These qualities were more strongly associated among those who
      followed celebrity suicide with intermediate and high effect sizes than lower.
      Younger suicide victims were significantly associated with higher effect size,
      female gender, white collar employment, unmarried status, higher education, death
      by hanging, and night-time death. Characteristics of celebrities were
      significantly associated with those of general population in hanging method and
      gender. CONCLUSION: Individuals who commit suicide after a celebrity suicide are
      likely to be younger, female, and prefer hanging as method of suicide, which are
      more strongly associated in higher effect sizes of celebrity suicide.

PMID- 25866522
TI  - A 2-year psychological autopsy study of completed suicides in the athens greater
      area, Greece.
AB  - OBJECTIVE: To study the characteristics of a sample of suicide victims from the
      Athens Greater Area using the psychological autopsy method for the first time in
      Greece. METHODS: We studied all recorded cases of completed suicide for the 2
      year time period November 2007-October 2009 collecting data from the victims'
      forensic records as well as from the completion of a psychological autopsy
      questionnaire. RESULTS: 335 persons were recorded as suicide victims. We
      contacted relatives of 256 victims interviewing those of 248 of them (96.9%). The
      differences regarding sex, marital and employment status between our sample and
      the general population were statistically significant (p<0.001). The male/female
      ratio was 3:1. Comparatively more victims were divorced, separated or single and
      a greater proportion were pensioners or unemployed. 26.0% of the victims had
      history of prior attempts (64.4% once, 20.3% twice and 15.3% more times). 42.6%
      were taking psychiatric medication-significantly more women than men according to
      blood tests; 14.2% had been hospitalized in a psychiatric clinic the year prior
      to their death. 84.8% have deceased at the place of suicide and 15.2% died in the
      hospital; 80.3% died indoors and 19.7% outdoors. Men died primarily by hanging or
      shooting by a firearm while women preferred jumping from height instead
      (p<0.001). As many as 48.8% had expressed their intention to die to their
      relatives; 26.6% left a suicide note. CONCLUSION: Our study has shown that the
      psychological autopsy method is applicable and widely accepted yielding results
      comparable to the international literature. Specific parameters associated with
      suicide have been studied for the first time in Greece.

PMID- 25866523
TI  - Validation of the mood and anxiety symptom questionnaire in korean adolescents.
AB  - OBJECTIVE: The tripartite model categorizes symptoms of depression and anxiety
      into three groups: 1) non-specific general distress that is shared between
      depression and anxiety, 2) depression-specific symptoms that include low positive
      affect and loss of interest, and 3) anxiety-specific symptoms that include
      somatic arousal. The Mood and Anxiety Symptoms Questionnaire (MASQ) was developed
      to measure these three factors of depression and anxiety. The purpose of the
      present study was to test the psychometric properties of the Korean version of
      the MASQ (K-MASQ) in adolescents. METHODS: Community-dwelling adolescents (n=933)
      were randomly assigned to two groups. Exploratory factor analysis and
      confirmatory factor analysis were conducted in each group to identify the factor
      structure of the K-MASQ. The reliability and validity of the K-MASQ were also
      evaluated. RESULTS: Our results support the three-factor structure of the K-MASQ
      in adolescents. However, we found that the specific items of each factor differed
      from those of the original MASQ. That is, the depression-specific factor was only
      related to low positive affect and not loss of interest, and the anxiety-specific
      factor included more items related to general somatic symptoms of anxiety. The
      reliability and validity of the K-MASQ were found to be satisfactory. CONCLUSION:
      The K-MASQ supports the tripartite model of depression and anxiety and has
      satisfactory reliability and validity among Korean adolescents. The K-MASQ can be
      used to distinguish unique symptoms of depression and anxiety in Korean
      adolescents.

PMID- 25866524
TI  - Increased cognition connectivity network in major depression disorder: a FMRI
      study.
AB  - OBJECTIVE: Evidence of the brain network involved in cognitive dysfunction has
      been inconsistent for major depressive disorder (MDD), especially during early
      stage of MDD. This study seeks to examine abnormal cognition connectivity network
      (CCN) in MDD within the whole brain. METHODS: Sixteen patients with MDD and 16
      health controls were scanned during resting-state using 3.0 T functional magnetic
      resonance imaging (fMRI). All patients were first episode without any history of
      antidepressant treatment. Both the left and right dorsolateral prefrontal cortex
      (DLPFC) were used as individual seeds to identify CCN by the seed-target
      correlation analysis. Two sample t test was used to calculate between-group
      differences in CCN using fisher z-transformed correlation maps. RESULTS: The CCN
      was constructed by bilateral seed DLPFC in two groups separately. Depressed
      subjects exhibited significantly increased functional connectivity (FC) by left
      DLPFC in one cluster, overlapping middle frontal gyrus, BA7, BA43, precuneus,
      BA6, BA40, superior temporal gyrus, BA22, inferior parietal lobule, precentral
      gyrus, BA4 and cingulate gyrus in left cerebrum. Health controls did not show any
      cluster with significantly greater FC compared to depressed subjects in left
      DLPFC network. There was no significant difference of FC in right DLPFC network
      between depressed subjects and the health controls. CONCLUSION: There are
      differences in CCN during early stage of MDD, as identified by increased FCs
      among part of frontal gyrus, parietal cortex, cingulate cortex, and BA43, BA22,
      BA4 with left DLPFC. These brain areas might be involved in the underlying
      mechanisms of cognitive dysfunction in MDD.

PMID- 25866525
TI  - Korean facial emotion recognition tasks for schizophrenia research.
AB  - OBJECTIVE: Despite the fact that facial emotion recognition (FER) tasks using
      Western faces should be applied with caution to non-Western participants or
      patients, there are few psychometrically sound and validated FER tasks featuring
      Easterners' facial expressions for emotions. Thus, we aimed to develop and
      establish the psychometric properties of the Korean Facial Emotion Identification
      Task (K-FEIT) and the Korean Facial Emotion Discrimination Task (K-FEDT) for
      individuals with schizophrenia. METHODS: The K-FEIT and K-FEDT were administered
      to 42 Korean individuals with schizophrenia to evaluate their psychometric
      properties. To test the convergent and divergent validities, the Social Behavior
      Sequencing Task (SBST) and hinting task were administered as social-cognitive
      measures, and the Trail Making Test (TMT)-A and -B were administered as
      neurocognitive measures. RESULTS: Average accuracy on the K-FEIT and K-FEDT were
      63% and 74%, respectively, and internal consistencies of the K-FEIT and K-FEDT
      were 0.82 and 0.95, respectively. The K-FEIT and K-FEDT were significantly
      correlated with SBST and Hinting Task, but not with TMT-A and B. CONCLUSION:
      Following replication studies in a larger sample, the K-FEIT and K-FEDT are
      expected to facilitate future studies targeting facial emotion recognition in
      schizophrenia in Korea. Limitations and directions for future research are
      discussed.

PMID- 25866526
TI  - Metabolic disturbances independent of body mass in patients with schizophrenia
      taking atypical antipsychotics.
AB  - OBJECTIVE: Atypical antipsychotic (AAP) treatment is associated with weight gain
      and metabolic disturbances such as dyslipidemia and dysglycemia. The metabolic
      disturbances are usually considered to develop secondary to weight gain. We
      performed the comparison of metabolic disturbances of three AAP group with
      different risk of metabolic side effect after adjusting for body mass to
      investigate whether any metabolic disturbances develop independently from body
      mass index (BMI). METHODS: This cross-sectional study included 174 subjects with
      schizophrenia who were on 1) monotherapy with clozapine (CL), olanzapine (OL), or
      quetiapine (QT) (n=61), 2) monotherapy with risperidone (RSP) (n=89), or 3)
      monotherapy with aripiprizole (ARP), or ziprasidone (ZPS) (n=24) more than 1
      year. Association between the prevalence of metabolic disturbances and groups
      were analysed using logistic regression after adjusting confounding variables
      including BMI. Analysese of covariance were used to compare the AAP groups in
      terms of the levels of metabolic parameters. RESULTS: There were significant
      differences among groups in terms of the prevalence of hypertriglyceridemia
      (p=0.015), low HDL-cholesterol (p=0.017), and hyperglycemia (p=0.022) after
      adjusting for BMI. Triglyceride level (p=0.014) and the ratio of triglyceride to
      HDL-cholesterol (p=0.004) were significantly different among groups after
      adjusting for BMI. CONCLUSION: In conclusion, metabolic disturbances are
      significantly different in AAP groups even after adjusting BMI. AAPs may have
      direct effect on metabolic parameters. Blood lipid and glucose levels should be
      monitored regularly regardless of whether patients tend to gain weight.

PMID- 25866527
TI  - Proteomic analysis of serum from patients with major depressive disorder to
      compare their depressive and remission statuses.
AB  - OBJECTIVE: Currently, there are a few biological markers to aid in the diagnosis
      and treatment of depression. However, it is not sufficient for diagnosis. We
      attempted to identify differentially expressed proteins during depressive moods
      as putative diagnostic biomarkers by using quantitative proteomic analysis of
      serum. METHODS: Blood samples were collected twice from five patients with major
      depressive disorder (MDD) at depressive status before treatment and at remission
      status during treatment. Samples were individually analyzed by liquid
      chromatography-tandem mass spectrometry for protein profiling. Differentially
      expressed proteins were analyzed by label-free quantification. Enzyme-linked
      immunosorbent assay (ELISA) results and receiver-operating characteristic (ROC)
      curves were used to validate the differentially expressed proteins. For
      validation, 8 patients with MDD including 3 additional patients and 8 matched
      normal controls were analyzed. RESULTS: The quantitative proteomic studies
      identified 10 proteins that were consistently upregulated or downregulated in 5
      MDD patients. ELISA yielded results consistent with the proteomic analysis for 3
      proteins. Expression levels were significantly different between normal controls
      and MDD patients. The 3 proteins were ceruloplasmin, inter-alpha-trypsin
      inhibitor heavy chain H4 and complement component 1qC, which were upregulated
      during the depressive status. The depressive status could be distinguished from
      the euthymic status from the ROC curves for these proteins, and this
      discrimination was enhanced when all 3 proteins were analyzed together.
      CONCLUSION: This is the first proteomic study in MDD patients to compare intra
      individual differences dependent on mood. This technique could be a useful
      approach to identify MDD biomarkers, but requires additional proteomic studies
      for validation.

PMID- 25866528
TI  - Serum S100B Protein Levels in Patients with Panic Disorder: Effect of Treatment
      with Selective Serotonine Reuptake Inhibitors.
AB  - OBJECTIVE: Altered serum S100B protein levels have been shown in several
      psychiatric disorders. Our aim was to investigate whether plasma S100B is
      different in patients with panic disorder (PD) when compared with controls. Our
      second aim was to investigate whether treatment with SSRIs have an effect on
      S100B levels in patients with PD. METHODS: The sample included 32 patients
      diagnosed with PD (21 women, 11 men) per DSM-IV criteria and 21 healthy controls
      (11 women, 10 men). S100B levels were measured with BioVendor Human S100B ELISA
      (Enzyme Linked Immunosorbent Assay) kit. RESULTS: 14 patients were not on drug
      treatment (43.8%) while 18 patients were taking various SSRIs. Median S100B value
      was 151.7 pg/mL (minimum-maximum: 120.4-164.7 pg/mL) in the control group, 147.4
      pg/mL (minimum-maximum: 138.8-154.1 pg/mL) in the drug free group and 153.0 pg/mL
      (minimum-maximum: 137.9-164.7 pg/mL) in the treatment group. Kruskal-Wallis
      analysis showed a significant diffrerence among the three groups (z=9.9, df=2,
      p=0.007). Follow up Mann-Whitney-U tests indicated that while the control and the
      patients with treatment were not significantly different (z=-0.05, p=0.96), there
      were significant differences between the control group and untreated patients (z=
      2.6, p=0.009) and treated and untreated patients (z=-3.0, p=0.003). CONCLUSION:
      Our results suggested that, serum S100B protein level might be decreased in
      untreated PD patients and that patients who were treated with SSRIs had similar
      S100B level to healthy controls.

PMID- 25866529
TI  - MEIS1, a Promising Candidate Gene, Is Not Associated with the Core Symptoms of
      Antipsychotic-Induced Restless Legs Syndrome in Korean Schizophrenia Patients.
AB  - OBJECTIVE: Restless legs syndrome (RLS) is a distressing sleep disorder to which
      individuals appear to be genetically predisposed. In the present study, we
      assumed that antipsychotic-induced RLS symptoms were attributable to differences
      in individual genetic susceptibility, and investigated whether MEIS1, a promising
      candidate gene, was associated with antipsychotic-induced RLS symptoms in
      schizophrenia patients. METHODS: All subjects were diagnosed with schizophrenia
      by board-certified psychiatrists using the Korean version of the Structured
      Clinical Interview for DSM-IV. We assessed antipsychotic-induced RLS symptoms in
      190 Korean schizophrenic patients using the diagnostic criteria of the
      International Restless Legs Syndrome Study Group. Genotyping was performed for
      the rs2300478 and rs6710341 polymorphisms of the MEIS1 gene. RESULTS: We divided
      subjects into RLS symptom (n=96) and non-symptom (n=94) groups. There was no
      significant between-group difference in the genotype or allele frequencies of the
      two polymorphisms investigated, nor in the frequency of the rs2300478-rs6710341
      haplotype. CONCLUSION: Our data do not suggest that the rs2300478 and rs6710341
      polymorphisms of the MEIS1 gene are associated with the core symptoms of
      antipsychotic-induced RLS in schizophrenia; different genetic mechanisms may
      underlie antipsychotic-induced vs. primary RLS.

PMID- 25866530
TI  - The Relationship between Depression, Anxiety, Somatization, Personality and
      Symptoms of Lower Urinary Tract Symptoms Suggestive of Benign Prostatic
      Hyperplasia.
AB  - This study investigated the relationship of personality, depression,
      somatization, anxiety with lower urinary tract symptoms suggestive of benign
      prostatic hyperplasia (LUTS/BPH). The LUTS/BPH patients were evaluated with the
      International Prostate Symptom Score (IPSS), 44-item Big Five Inventory (BFI),
      the Patient Health Questionnaire-9 (PHQ-9), the PHQ-15, and 7-item Generalized
      Anxiety Disorder Scale (GAD-7). The LUTS/BPH symptoms were more severe in
      patients with depression (p=0.046) and somatization (p=0.024), respectively.
      Neurotic patients were associated with greater levels of depression, anxiety and
      somatisation (p=0.0059, p=0.004 and p=0.0095, respectively). Patients with high
      extraversion showed significantly low depression (p=0.00481) and anxiety
      (p=0.035) than those with low extraversion. Our exploratory results suggest
      patients with LUTS/BPH may need careful evaluation of psychiatric problem
      including depression, anxiety and somatization. Additional studies with adequate
      power and improved designs are necessary to support the present exploratory
      findings. 

PMID- 25866531
TI  - Psychiatric symptoms in temporal lobe epilepsy with left mesial hippocampal
      sclerosis.
AB  - A 16-year-old woman was referred to us for depression and persistent suicidal and
      homicidal ideation. From 2010, the patient visited a neurologist due to recurrent
      grand mal epilepsy, auditory and visual hallucinations, episodic memory loss, and
      persistent depression. Upon admission, it was revealed through clinical history
      taking that she had suffered from chronic bullying from same-sex peers and sexual
      abuse, twice, from an adult male in the neighborhood when she was 10 years old. A
      brain magnetic resonance imaging study showed left mesial hippocampal sclerosis.
      The patient exhibited improvement of her psychiatric symptoms after treatment
      with a combination of fluoxetine (30 mg) and aripiprazole (10 mg). Children and
      adolescents with epilepsy experience conflicts in the family, challenges at
      school, stigma, and psychosocial limitations or deprivations due to their
      comorbid psychiatric symptoms and hence, psychiatric evaluation and early
      intervention is important when treating these patients. 

PMID- 25866532
TI  - Evidence-based treatment for depressive disorder.

PMID- 25866533
TI  - Jasada bhasma, a Zinc-Based Ayurvedic Preparation: Contemporary Evidence of
      Antidiabetic Activity Inspires Development of a Nanomedicine.
AB  - The roles of metals in human physiology are well established. It is also known
      that many metals are required in trace amounts for normal metabolism and their
      deficiency leads to diseases. In Ayurveda, metal-based preparations, that is,
      bhasmas, are indicated for the treatment of several diseases. Standard textbooks
      of Ayurveda recommend Jasada bhasma (zinc based bhasma) as the treatment of
      choice for diabetes. Modern medicine also recognizes the important role of zinc
      in glucose homeostasis. Yet, studies that validate the use of Jasada bhasma are
      few and uncomprehensive. There is an imminent need for a systematic study on
      physicochemical characterization, pharmacological efficacy, and toxicity
      assessment of several bhasma preparations to generate scientific evidence of
      their utility and safety. Interestingly, recent studies suggest that bhasmas
      comprise submicronic particles or nanoparticles. Thus a bhasma-inspired new drug
      discovery approach could emerge in which several metal based nanomedicines could
      be developed. This would help in utilizing the age old, time-tested wisdom of
      Ayurveda in modern medicine. One such study on antidiabetic activity of Jasada
      bhasma and the corresponding new drug, namely, zinc oxide nanoparticles, is
      briefly discussed, as an example. 

PMID- 25866534
TI  - Berberine nanosuspension enhances hypoglycemic efficacy on streptozotocin induced
      diabetic C57BL/6 mice.
AB  - Berberine (Ber), an isoquinoline derivative alkaloid and active ingredient of
      Coptis, has been demonstrated to possess antidiabetic activities. However its low
      oral bioavailability restricts its clinical application. In this report, Ber
      nanosuspension (Ber-NS) composed of Ber and D-alpha-tocopheryl polyethylene
      glycol 1000 succinate (TPGS) was prepared by high pressure homogenization
      technique. Antidiabetic effects of Ber-NS relative to efficacy of bulk Ber were
      evaluated in streptozotocin (STZ) induced diabetic C57BL/6 mice. The particle
      size and zeta potential of Ber-NS were 73.1 +/- 3.7 nm and 6.99 +/- 0.17 mV,
      respectively. Ber-NS (50 mg/kg) treatment via oral gavage for 8 weeks resulted in
      a superior hypoglycemic and total cholesterol (TC) and body weight reduction
      effects compared to an equivalent dose of bulk Ber and metformin (Met, 300
      mg/kg). These data indicate that a low dosage Ber-NS decreases blood glucose and
      improves lipid metabolism in type 2 diabetic C57BL/6 mice. These results suggest
      that the delivery of Ber as a nanosuspension is a promising approach for treating
      type 2 diabetes. 

PMID- 25866535
TI  - Anti-Inflammatory Effects of Monoammonium Glycyrrhizinate on Lipopolysaccharide
      Induced Acute Lung Injury in Mice through Regulating Nuclear Factor-Kappa B
      Signaling Pathway.
AB  - The present study aimed to investigate the therapeutic effect of monoammonium
      glycyrrhizinate (MAG) on lipopolysaccharide- (LPS-) induced acute lung injury
      (ALI) in mice and possible mechanism. Acute lung injury was induced in BALB/c
      mice by intratracheal instillation of LPS, and MAG was injected intraperitoneally
      1 h prior to LPS administration. After ALI, the histopathology of lungs, lung
      wet/dry weight ratio, protein concentration, and inflammatory cells in the
      bronchoalveolar lavage fluid (BALF) were determined. The levels of tumor necrosis
      factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) in the BALF were
      measured by ELISA. The activation of NF-kappaB p65 and IkappaB-alpha of lung
      homogenate was detected by Western blot. Pretreatment with MAG attenuated lung
      histopathological damage induced by LPS and decreased lung wet/dry weight ratio
      and the concentrations of protein in BALF. At the same time, MAG reduced the
      number of inflammatory cells in lung and inhibited the production of TNF-alpha
      and IL-1beta in BALF. Furthermore, we demonstrated that MAG suppressed activation
      of NF-kappaB signaling pathway induced by LPS in lung. The results suggested that
      the therapeutic mechanism of MAG on ALI may be attributed to the inhibition of NF
      kappaB signaling pathway. Monoammonium glycyrrhizinate may be a potential
      therapeutic reagent for ALI. 

PMID- 25866536
TI  - Naturally occurring anthraquinones: chemistry and therapeutic potential in
      autoimmune diabetes.
AB  - Anthraquinones are a class of aromatic compounds with a 9,10-dioxoanthracene
      core. So far, 79 naturally occurring anthraquinones have been identified which
      include emodin, physcion, cascarin, catenarin, and rhein. A large body of
      literature has demonstrated that the naturally occurring anthraquinones possess a
      broad spectrum of bioactivities, such as cathartic, anticancer, anti
      inflammatory, antimicrobial, diuretic, vasorelaxing, and phytoestrogen
      activities, suggesting their possible clinical application in many diseases.
      Despite the advances that have been made in understanding the chemistry and
      biology of the anthraquinones in recent years, research into their mechanisms of
      action and therapeutic potential in autoimmune disorders is still at an early
      stage. In this paper, we briefly introduce the etiology of autoimmune diabetes,
      an autoimmune disorder that affects as many as 10 million worldwide, and the role
      of chemotaxis in autoimmune diabetes. We then outline the chemical structure and
      biological properties of the naturally occurring anthraquinones and their
      derivatives with an emphasis on recent findings about their immune regulation. We
      discuss the structure and activity relationship, mode of action, and therapeutic
      potential of the anthraquinones in autoimmune diabetes, including a new strategy
      for the use of the anthraquinones in autoimmune diabetes. 

PMID- 25866537
TI  - Study of the Gastroprotective Effect of Extracts and Semipurified Fractions of
      Chresta martii DC. and Identification of Its Principal Compounds.
AB  - Chresta martii (Asteraceae) is a species widely used by the population of the
      Xingu region of Sergipe, Brazil, in the form of a decoction (aerial parts) for
      the treatment of gastrointestinal diseases. The study aims to assess the
      gastroprotective activity of organic extracts and semipurified fractions and
      identify the principal compounds present in C. martii responsible for such
      activity. The organic extracts (cyclohexane: ECCm, ethyl acetate: EACm, and
      ethanol: EECm) were obtained from the dried aerial parts (500 g) of C. martii.
      For evaluation of the gastroprotective activity of extracts (50, 100, or 200
      mg/kg; p.o.), male Swiss Webster mice (25-30 g) were used which had gastric
      ulcers induced by indomethacin (40 mg/kg, s.c.) or ethanol (0.2 mL/animal; p.o.).
      Among the extracts evaluated, EACm exhibited significant (P < 0.05)
      gastroprotective activity in the models used. The fractionation of EACm was
      performed in a silica gel column 60 eluted with the following compounds:
      [chloroform-F1 yield (10%)], [chloroform/ethyl acetate (1/1)-F2 yield (6%)],
      [ethyl acetate-F3 yield (8%)], and [ethyl/methanol acetate (1/1)-F4 yield (5%)].
      Of the fractions described above, the F1 (25 mg/kg; p.o.) had greater
      gastroprotective activity (P < 0.05) than that displayed by ranitidine (80 mg/kg;
      p.o.) in the ethanol-induced ulcer model. The refractionation of F1 produced 23
      subfractions and from these two yellow amorphous compounds were obtained by
      recrystallization, Rf: 0.46 and 0.31 (ethyl acetate : chloroform 5 : 5). The
      compounds isolated were characterized by nuclear magnetic resonance spectroscopy
      ((1)H-NMR and (13)C-NMR) and identified as flavones: chrysoeriol (yield: 0.43%)
      and 3',4'-dimethoxyluteolin (yield: 0.58%). Conclusion. Flavone 3',4'
      dimethoxyluteolin is the principal compound present in the species C. martii and
      is probably responsible for gastroprotective activity observed in this species. 

PMID- 25866538
TI  - Early Steroid-Induced Osteonecrosis of Rabbit Femoral Head and Panax notoginseng
      Saponins: Mechanism and Protective Effects.
AB  - Background. This study was aimed at investigating the pathogenesis of oxidative
      stress in steroid-induced avascular necrosis of the femoral head (SANFH) and at
      exploring the mechanism and protective effects of Panax notoginseng saponins
      (PNS) on early SANFH. Methods. 80 adult New Zealand rabbits were randomly divided
      into control group, model group, and PNS group. In model group, equine serum was
      injected into auricular vein; then methylprednisolone was injected into gluteus.
      In PNS group, PNS was applied for 14 consecutive days before methylprednisolone
      management. At different time points, serum and femoral heads were prepared for T
      AOC, SOD, GSH-PX, .OH, and MDA determination. Two weeks after steroid management,
      all femoral heads were assessed with MRI and HE staining. Results. Typical early
      osteonecrosis symptoms were observed in model group. Our results showed that PNS
      could significantly ameliorate the decrease of T-AOC level, improve SOD and GSH
      PX activity, suppress .OH ability, and augment MDA level. Besides, PNS improved
      MRI and pathological changes of the femoral head, markedly reducing the incidence
      of osteonecrosis. Conclusion. Based on our research, we found oxidative stress
      played a positive role in the occurrence of SANFH where reactive oxygen species
      was the direct cause. PNS could protect rabbits against early steroid-induced
      osteonecrosis of femoral head by its antioxidative effect. 

PMID- 25866539
TI  - The Efficiency of Barley (Hordeum vulgare) Bran in Ameliorating Blood and
      Treating Fatty Heart and Liver of Male Rats.
AB  - The current study focused on testing the hypolipidemic activity of two doses of
      barley bran on hypercholesterolemic male rats. Twenty-four male albino rats
      weighing 180-200 gm were divided into four groups. The first group (G1) was the
      negative control, the second group (G2) was the positive control group fed 2%
      cholesterol in the diet, and rats of the third and the fourth groups were fed 2%
      cholesterol and were cosupplemented with 5% and 10% barley bran, respectively,
      for 8 weeks. The hypercholesterolemic rats of (G2) showed an increase in lipid
      profile, liver enzymes, lactate dehydrogenase, creatine kinase-MB, and lipid
      peroxide and a decrease in antioxidant enzymes, whereas kidney function, fasting
      blood sugar, glycated hemoglobin total protein, and total bilirubin were not
      significantly affected compared with the negative control group in G1. Moreover,
      histology of heart, liver, and kidney of G2 rats showed histopathological changes
      compared with the negative control. Administration of the two doses of barley
      bran in G3 and G4 to the hypercholesterolemic rats ameliorated the level of
      lipids, liver enzymes, lactate dehydrogenase, and creatine kinase-MB. In
      addition, the histology of heart, liver, and kidney tissues nearly restored the
      normal state as in G1. 

PMID- 25866540
TI  - Effects of Shengjiang (Zingiberis Rhizoma Recens) and Its Processed Products on
      Nitric Oxide Production in Macrophage RAW 264.7 Cells.
AB  - In Chinese medicine, Shengjiang (Zingiberis Rhizoma Recens) and its processed
      products, such as Ganjiang (Zingiberis Rhizoma), Paojiang (Zingiberis Rhizoma
      Preparatum), and Jiangtan (Zingiberis Rhizoma Carbonisata), exert distinct
      efficacy clinically. This research tried to study the effects of extracts from
      Shengjiang and its processed products in RAW 264.7 macrophage cells. After
      incubation of the different ginger types in RAW 264.7 cells for 24 h, an aliquot
      of the culture was mixed with an equal volume of Griess reagent, and nitric oxide
      (NO) production was evaluated using a Griess assay. Lipopolysaccharide (LPS) was
      used as the positive control. Milli-Q water (MQW) was used as the solvent
      control. The results showed that NO production increased significantly in RAW
      264.7 cells following the stimulation of LPS (0.05 MUg mL(-1)), Shengjiang,
      Ganjiang, Paojiang, and Jiangtan (50 MUg mL(-1), 500 MUg mL(-1)) separately
      compared with the MQW control (P < 0.01). The stimulation effects of Shengjiang
      and Ganjiang were significantly higher than those of Paojiang and Jiangtan at
      different concentrations (P < 0.01). The conclusion we could get from this
      research is that Shengjiang and its processed products could induce NO production
      in RAW 264.7 cells. 

PMID- 25866541
TI  - Bidens pilosa Formulation Improves Blood Homeostasis and beta -Cell Function in
      Men: A Pilot Study.
AB  - B. pilosa has long been purported to have antidiabetes activity, but despite the
      advancement in phytochemistry and animal models of diabetes, no human clinical
      trials have been conducted to date. Here, we evaluated the effect of a B. pilosa
      formulation on fasting blood glucose (FBG), fasting serum insulin, and
      glycosylated hemoglobin A1c (HbA1c) in diabetic subjects. The B. pilosa
      formulation reduced the level of FBG and HbA1c in diabetics but increased fasting
      serum insulin in healthy subjects. Moreover, combination of B. pilosa formulation
      with antidiabetic drugs had better glycemic control in diabetics. The homeostatic
      model assessment (HOMA) data suggested that the antidiabetic activity of this
      formulation was via improvement of beta-cell function. We also tested the safety
      of the B. pilosa formulation in healthy subjects and observed no obvious side
      effects. We conclude that B. pilosa has potential as an antidiabetes treatment. 

PMID- 25866542
TI  - Gambogic Acid lysinate induces apoptosis in breast cancer mcf-7 cells by
      increasing reactive oxygen species.
AB  - Gambogic acid (GA) inhibits the proliferation of various human cancer cells.
      However, because of its water insolubility, the antitumor efficacy of GA is
      limited. Objectives. To investigate the antitumor activity of gambogic acid
      lysinate (GAL) and its mechanism. Methods. Inhibition of cell proliferation was
      determined by MTT assay; intracellular ROS level was detected by staining cells
      with DCFH-DA; cell apoptosis was determined by flow cytometer and the mechanism
      of GAL was investigated by Western blot. Results. GAL inhibited the proliferation
      of MCF-7 cells with IC50 values 1.46 MUmol/L comparable with GA (IC50, 1.16
      MUmol/L). GAL promoted the production of ROS; however NAC could remove ROS and
      block the effect of GAL. GAL inhibited the expression of SIRT1 but increased the
      phosphorylation of FOXO3a and the expression of p27Kip1. At knockdown of FOXO3a,
      cell apoptosis induced by GAL can be partly blocked. In addition it also enhanced
      the cleavage of caspase-3. Conclusions. GAL inhibited MCF-7 cell proliferation
      and induced MCF-7 cell apoptosis by increasing ROS level which could induce cell
      apoptosis by both SIRT1/FOXO3a/p27Kip1 and caspase-3 signal pathway. These
      results suggested that GAL might be useful as a modulation agent in cancer
      chemotherapy. 

PMID- 25866543
TI  - Antitumor Activities of Ethyl Acetate Extracts from Selaginella doederleinii
      Hieron In Vitro and In Vivo and Its Possible Mechanism.
AB  - The antitumor activities of ethyl acetate extracts from Selaginella doederleinii
      Hieron (SD extracts) in vitro and in vivo and its possible mechanism were
      investigated. HPLC method was developed for chemical analysis. SD extracts were
      submitted to 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT)
      assay on different cells, flow cytometry, and RT-PCR analysis using HepG2 cell
      and antitumor activity in vivo using H-22 xenograft tumor mice. Six biflavonoids
      from SD extracts were submitted to molecular docking assay. The results showed
      that SD extracts had considerable antitumor activity in vitro and in vivo without
      obvious toxicity on normal cells and could induce cell apoptosis. The mechanisms
      of tumorigenesis and cell apoptosis induced by SD extracts may be associated with
      decreasing the ratio of bcl-2 and bax mRNA level, activating caspase-3,
      suppressing survivin, and decreasing the gene expression of COX-2, 5-LOX, FLAP,
      and 12-LOX mRNA. The main active component in SD extracts is biflavonoids and
      some exhibited strong interactions with COX-2, 5-LOX, 12-LOX, and 15-LOX. These
      results offering evidence of possible mechanisms of SD extracts suppress cell
      proliferation and promote apoptosis and provide the molecular theoretical basis
      of clinical application of S. doederleinii for cancer therapy. 

PMID- 25866544
TI  - Yokukansan Improves Mechanical Allodynia through the Regulation of Interleukin-6
      Expression in the Spinal Cord in Mice with Neuropathic Pain.
AB  - Neuropathic pain is caused by nerve injury. Yokukansan (Yi-Gan San), a
      traditional Japanese (Kampo) medicine, has been widely used for neuropathic pain
      control. However, the analgesic mechanisms remain unknown. In this study, we
      investigated the analgesic mechanisms of yokukansan in a mouse model of
      neuropathic pain. Partial sciatic nerve ligation (PSL) induced mechanical
      allodynia in mice. Repetitive oral administration of the extracts of yokukansan
      and the constituent herbal medicine Atractylodis Lanceae Rhizoma, but not
      Glycyrrhizae Radix, relieved mechanical allodynia in the PSL mice and inhibited
      the PSL-induced expression of interleukin- (IL-) 6 mRNA in the spinal cord.
      Yokukansan did not attenuate intrathecal IL-6-induced mechanical allodynia. IL-6
      immunoreactivity was detected in microglia and astrocytes in the spinal dorsal
      horn. These results suggest that yokukansan relieves mechanical allodynia in PSL
      mice by regulating the expression of IL-6 in astrocytes and/or microglia in the
      spinal cord. In addition, the components of Atractylodis Lanceae Rhizoma, one of
      the constituent herbal medicines in yokukansan, may play an important role in the
      regulation of IL-6 expression and neuropathic pain control. 

PMID- 25866545
TI  - A training, assessment and feedback package for the trainee shoulder sonographer.
AB  - Diagnostic ultrasound of the shoulder is recognised as being one of the most
      technically challenging aspects of musculoskeletal ultrasound to master. It has a
      steep learning curve and makes gaining competency a time-intensive training
      process for both the trainee and their trainer. This article describes a
      training, assessment and feedback package developed within the framework of a
      Consortium for the Accreditation of Sonographic Education approved post-graduate
      ultrasound course. The package comprises: (i) a shoulder diagnostic ultrasound
      scan protocol with definition of findings, differential diagnosis and pro forma
      for recording scan findings, (ii) an assessment form for performance of shoulder
      diagnostic ultrasound scans with assessment criteria and (iii) a combined
      performance assessment and scan findings form, for each tissue being imaged. The
      package has been developed using medical education principles and provides a
      mechanism for trainees to follow an internationally recognised protocol.
      Supplementary information includes the differential diagnostic process used by an
      expert practitioner, which can otherwise be difficult to elicit. The package
      supports the trainee with recording their findings quickly and consistently and
      helps the trainee and trainer to explicitly recognise the challenges of scanning
      different patients or pathologies. It provides a mechanism for trainers to
      quantify and trainees to evidence their emerging competency. The package detailed
      in this article is therefore proposed for use in shoulder ultrasound training and
      its principles could be adapted for other musculoskeletal regions or other
      ultrasound disciplines.

PMID- 25866546
TI  - pH-triggered self-assembly of biocompatible histamine-functionalized triblock
      copolymers.
AB  - Histamine functionalized poly(allyl glycidyl ether)-b-poly(ethylene glycol)-b
      poly(allyl glycidyl ether) (PAGE-PEO-PAGE) triblock copolymers represent a new
      class of physically cross-linked, pH-responsive hydrogels with significant
      potential for biomedical applications. These telechelic triblock copolymers
      exhibited abrupt and reversible hydrogelation above pH 7.0 due to a
      hudrophilic/hydrophobic transition of the histamine units to form a network of
      hydrophobic domains bridged by a hydrophilic PEO matrix. These hydrophobic
      domains displayed improved ordering upon increasing pH and self-assembled into a
      body centered cubic lattice at pH 8.0, while at lower concentrations formed well
      defined micelles. Significantly, all materials were found to be non-toxic when
      evaluated on three different cell lines and suggests a range of medical and
      biomedical applications.

PMID- 25866547
TI  - A study of the association between urinary aluminum concentration and pre
      clinical findings among aluminum-handling and non-handling workers.
AB  - BACKGROUND: Aluminum is considered to be a relatively safe metal for humans.
      However, there are some reports that aluminum can be toxic to humans and animals.
      In order to estimate the toxicity of aluminum with respect to humans, we measured
      the aluminum concentration in urine of aluminum-handling and non-handling workers
      and investigated the relationships between their urinary aluminum concentrations
      and pre-clinical findings. METHODS: Twenty-three healthy aluminum-handling
      workers and 10 healthy non-aluminum-handling workers participated in this study.
      Their medical examinations, which were otherwise unremarkable, included the
      collection of urine and blood. Urinary aluminum levels were analyzed using ICP
      analysis. As pre-clinical tests, we measured KL-6, SP-D, TRCP-5b, IL-6, and IL-8
      in blood and delta-ALA and beta2-microglobulin in urine. These were considered to
      be lung, bone, kidney and inflammation markers. Moreover, we measured 8-OHdG in
      urine as an oxidative DNA damage marker. RESULTS: The aluminum concentration in
      urine ranged from 6.9 to 55.1 MUg/g cre (median: 20.1 MUg/g cre) in the aluminum
      handling workers and from 5.6 to 15.6 MUg/g cre (median: 8.8 MUg/g cre) in the
      non-aluminum-handling workers, with a significant difference between them. In the
      pre-clinical findings, there were no significant differences between these two
      groups except in the case of delta-ALA. However, there were no significant
      relationships between aluminum concentration and the pre-clinical findings, work
      years, age or 8-OHdG in the aluminum-handling workers. CONCLUSIONS: While the
      excretion of aluminum in urine was elevated in aluminum-handling workers, our
      findings suggest that low-dose aluminum is not directly harmful to humans, at
      least when workers' urinary aluminum concentration is below 55 MUg/g cre.

PMID- 25866548
TI  - Loneliness: clinical import and interventions.
AB  - In 1978, when the Task Panel report to the US President's Commission on Mental
      Health emphasized the importance of improving health care and easing the pain of
      those suffering from emotional distress syndromes including loneliness, few
      anticipated that this issue would still need to be addressed 40 years later. A
      meta-analysis (Masi et al., 2011) on the efficacy of treatments to reduce
      loneliness identified a need for well-controlled randomized clinical trials
      focusing on the rehabilitation of maladaptive social cognition. We review
      assessments of loneliness and build on this meta-analysis to discuss the efficacy
      of various treatments for loneliness. With the advances made over the past 5
      years in the identification of the psychobiological and pharmaceutical mechanisms
      associated with loneliness and maladaptive social cognition, there is increasing
      evidence for the potential efficacy of integrated interventions that combine
      (social) cognitive behavioral therapy with short-term adjunctive pharmacological
      treatments. 

PMID- 25866549
TI  - Phenoplant: a web resource for the exploration of large chlorophyll fluorescence
      image datasets.
AB  - BACKGROUND: Image analysis is increasingly used in plant phenotyping. Among the
      various imaging techniques that can be used in plant phenotyping, chlorophyll
      fluorescence imaging allows imaging of the impact of biotic or abiotic stresses
      on leaves. Numerous chlorophyll fluorescence parameters may be measured or
      calculated, but only a few can produce a contrast in a given condition.
      Therefore, automated procedures that help screening chlorophyll fluorescence
      image datasets are needed, especially in the perspective of high-throughput plant
      phenotyping. RESULTS: We developed an automatic procedure aiming at facilitating
      the identification of chlorophyll fluorescence parameters impacted on leaves by a
      stress. First, for each chlorophyll fluorescence parameter, the procedure
      provides an overview of the data by automatically creating contact sheets of
      images and/or histograms. Such contact sheets enable a fast comparison of the
      impact on leaves of various treatments, or of the contrast dynamics during the
      experiments. Second, based on the global intensity of each chlorophyll
      fluorescence parameter, the procedure automatically produces radial plots and box
      plots allowing the user to identify chlorophyll fluorescence parameters that
      discriminate between treatments. Moreover, basic statistical analysis is
      automatically generated. Third, for each chlorophyll fluorescence parameter the
      procedure automatically performs a clustering analysis based on the histograms.
      This analysis clusters images of plants according to their health status. We
      applied this procedure to monitor the impact of the inoculation of the root
      parasitic plant Phelipanche ramosa on Arabidopsis thaliana ecotypes Col-0 and
      Ler. CONCLUSIONS: Using this automatic procedure, we identified eight chlorophyll
      fluorescence parameters discriminating between the two ecotypes of A. thaliana,
      and five impacted by the infection of Arabidopsis thaliana by P. ramosa. More
      generally, this procedure may help to identify chlorophyll fluorescence
      parameters impacted by various types of stresses. We implemented this procedure
      at http://www.phenoplant.org freely accessible to users of the plant phenotyping
      community.

PMID- 25866550
TI  - A software tool for the input and management of phenotypic data using personal
      digital assistants and other mobile devices.
AB  - BACKGROUND: Plant breeding and genetics demand fast, exact and reproducible
      phenotyping. Efficient statistical evaluation of phenotyping data requires
      standardised data storage ensuring long-term data availability while maintaining
      intellectual property rights. This is state of the art at phenomics centres,
      which, however, are unavailable for most scientists. For them we developed a
      simple and cost-efficient system, the Phenotyper, which employs mobile devices or
      personal digital assistants (PDA) for on-site data entry and open-source software
      for data management. RESULTS: A graphical user interface (GUI) on a PDA replaces
      paper-based form sheet and data entry on a desktop. The user can define his
      phenotyping schemes in a web tool without in-depth knowledge of the system and
      thus adjust it more easily to new research aspects than in a classical laboratory
      information management system (LIMS). In the Phenotyper, schemes are built from
      controlled vocabulary gained from published ontologies. Vocabulary and schemes
      are stored in a database that also manages the user access. From the web page,
      schemes are downloaded as extended markup language (XML) files for the transfer
      to the PDA and the exchange between users. On the PDA, the GUI displays the
      schemes and stores data in comma separated value format and XML format. After
      manual quality control, data are uploaded via a web page to an independently
      hosted results database, in which data are stored in an entity-attribute-value
      structure to provide maximum flexibility. Datasets are linked to the original and
      curated data files stored on a file server. The ownership stamp, project
      affiliation and date stamp of a dataset are used to regulate data access, which
      is restricted to data belonging to the user or to his projects and data, for
      which the embargo period has ended. By export of standardised ASCII reports to
      long-term data storage facility, long-term accessibility allows searching, citing
      and use of raw data beyond the lifetime of the database. The Phenotyper is
      available to the scientific community for use and further development.
      CONCLUSIONS: The Phenotyper provides a well-structured, but flexible data
      acquisition and management structure for mobile on-site measurements for
      efficient evaluation and shared use of data.

PMID- 25866551
TI  - Proline-Directed Androgen Receptor Phosphorylation.
AB  - The androgen receptor (AR) has been identified for decades and mediates essential
      steroid functions. Like most of biological molecules, AR functional activities
      are modulated by post-translational modifications. This review is focused on the
      reported activities and significance of AR phosphorylation, with particular
      emphasis on proline-directed serine/threonine phosphorylation that occurs
      predominantly on the receptor. The marked enrichment of AR phosphorylation in the
      most diverse N-terminal domain suggests that targeting AR phosphorylation can be
      synergistic to antagonizing the C-terminal domain by clinical antiandrogens.

PMID- 25866552
TI  - A Multilayered Cell Culture Model for Transport Study in Solid Tumors: Evaluation
      of Tissue Penetration of Polyethyleneimine Based Cationic Micelles.
AB  - Limited drug distribution is partially responsible for the efficacy gap between
      preclinical and clinical studies of nano-sized drug carriers for cancer therapy.
      In this study, we examined the transport behavior of cationic micelles formed
      from a triblock copolymer of poly(D,L-lactide-co-glycolide)-block-branched
      polyethyleneimine-block-poly(D,L-lactide-co-glycolide) using a unique in vitro
      tumor model composed of a multilayered cell culture (MCC) and an Ussing chamber
      system. The Cy3-labeled cationic micelles showed remarkable Cy3 distribution in
      the MCC whereas charge-shielded micelles with a poly(ethylene glycol) surface
      accumulated on the surface of the MCC. Penetration occurred against convectional
      flow caused by a hydraulic pressure gradient. The study using fluorescence
      resonance energy transfer (FRET) showed that the cationic micelles dissociate at
      the interface between the culture media and the MCC or possibly inside of the
      first-layer cells and penetrates into the MCC as unimers. The penetration and
      distribution were energy-dependent and suppressed by various endocytic
      inhibitors. These suggest that cationic unimers mainly utilized clathrin-mediated
      endocytosis and macropinocytosis for cellular entry and a significant fraction
      were exocytosed by an unknown mechanism.

PMID- 25866553
TI  - Finding top-k covering irreducible contrast sequence rules for disease diagnosis.
AB  - Diagnostic genes are usually used to distinguish different disease phenotypes.
      Most existing methods for diagnostic genes finding are based on either the
      individual or combinatorial discriminative power of gene(s). However, they both
      ignore the common expression trends among genes. In this paper, we devise a novel
      sequence rule, namely, top-k irreducible covering contrast sequence rules
      (TopkIRs for short), which helps to build a sample classifier of high accuracy.
      Furthermore, we propose an algorithm called MineTopkIRs to efficiently discover
      TopkIRs. Extensive experiments conducted on synthetic and real datasets show that
      MineTopkIRs is significantly faster than the previous methods and is of a higher
      classification accuracy. Additionally, many diagnostic genes discovered provide a
      new insight into disease diagnosis. 

PMID- 25866554
TI  - Physical activities of Patients with adolescent idiopathic scoliosis (AIS):
      preliminary longitudinal case-control study historical evaluation of possible
      risk factors.
AB  - To our knowledge there are no publications that have evaluated physical
      activities in relation to the etiopathogenesis of adolescent idiopathic scoliosis
      (AIS) other than sports scolioses. In a preliminary longitudinal case-control
      study, mother and child were questioned and the children examined by one
      observer. The aim of the study was to examine possible risk factors for AIS. Two
      study groups were assessed for physical activities: 79 children diagnosed as
      having progressive AIS at one spinal deformity centre (66 girls, 13 boys) and a
      Control Group of 77 school children (66 girls, 11 boys), the selection involving
      six criteria. A structured history of physical activities was obtained, every
      child allocated to a socioeconomic group and examined for toe touching. Unlike
      the Patients, the Controls were not X-rayed and were examined for surface
      vertical spinous process asymmetry (VSPA). Statistical analyses showed
      progressive AIS to be positively associated with social deprivation, early
      introduction to indoor heated swimming pools and ability to toe touch. AIS is
      negatively associated with participation in dance, skating, gymnastics or karate
      and football or hockey classes, which might suggest preventive possibilities.
      There is a significantly increased independent odds of AIS in children who went
      to an indoor heated swimming pool within the first year of life (odds ratio 3.88,
      95% CI 1.77-8.48; p = 0.001). Furthermore fourteen (61%) Controls with VSPA
      compared with 9 (17%) Controls without VSPA had been introduced to the swimming
      pool within their first year of life (P < 0.001). Early exposure to indoor heated
      swimming pools for both AIS and VSPA, suggests that the AIS findings do not
      result from sample selection. 

PMID- 25866557
TI  - Rings or daggers, axes or fibulae have a different composition? A multivariate
      study on Central Italy bronzes from eneolithic to early iron age.
AB  - BACKGROUND: One of the main concerns for archaeo-metallurgists and archaeologists
      is to determine to what extent ancient craftsmen understood the effect of metal
      alloy composition and were able to control it in order to produce objects with
      the most suitable features. This problem can be investigated by combining
      compositional analyses of a high number of ancient artefacts with correlation
      analyses of the objects' age, production site, destination of usage etc. - and
      thus chemometric data treatment is carried out. In this study, multivariate
      analyses were performed on a matrix composed of elemental compositional data from
      134 archaeological bronze objects, obtained by XRF analyses. Analysed objects
      have been dated back from the Eneolithic Period to the end of the Bronze Age
      including the early Iron Age and were excavated in Central Italy (mainly Abruzzo
      Region). RESULTS: Chemometric analysis was performed attempting to visualise
      clouds of objects through PCA. In parallel and independently, object grouping was
      attempted using several different approaches, based on object characteristics
      (e.g. shape, weight, type of use - cutting or hitting and age) following
      indications given by archaeologists (or derived from the archaeological context).
      Furthermore, case-tailored data pretreatment (logratio-centred scaling) was used,
      but no homogeneous groups could be identified. CONCLUSIONS: By using chemometric
      data analysis, homogeneous groups of objects could not be detected, meaning that
      compositional data of alloys is not correlated with the considered objects'
      characteristics. This favours the conclusion that - without discussing the
      ascertained ability of ancient foundry-men - they had also already discovered the
      convenience of recycling broken objects thus producing a more or less similar
      bronze alloy each time, depending on materials' availability; necessary
      mechanical characteristics could then be obtained by post processing. Graphical
      AbstractScores PCA plot in 3D space with 3 different bronze objects.

PMID- 25866556
TI  - Wormpath: searching for molecular interaction networks in Caenorhabditis elegans.
AB  - BACKGROUND: High-throughput transcriptional profiling using Next-Generation
      Sequencing (RNA-Seq) or microarray technology have become standard tools in
      molecular biology. Successful investigations of gene regulatory mechanisms from
      these data typically employ mathematical models of biological networks. RESULTS:
      We have developed Wormpath, a software for molecular network discovery which
      operates on the genetic and physical interaction data of the Wormbase, a
      comprehensive resource of molecular data on Caenorhabditis elegans. We use
      Wormpath to show that the insulin/insulin-like growth factor signalling (IIS)
      pathway responds to UV-induced DNA damage during development. CONCLUSIONS: Our
      software provides highly facilitated access to C. elegans interaction data and is
      capable of identifying essential molecular networks within a list of
      differentially expressed genes.

PMID- 25866555
TI  - Non operative management of traumatic esophageal perforation leading to
      esophagocutaneous fistula in pediatric age group: review and case report.
AB  - Management of delayed presenting esophageal perforations has long been a topic of
      debate. Most authors consider definitive surgery being the management of choice.
      Management, however, differs in pediatric patients in consideration with better
      healing of younger tissues. We extensively review the role of aggressive non
      operative management in pediatric esophageal perforations, especially with
      delayed presentation and exemplify with case of a young boy with esophageal
      perforation and esophago-cutaneous fistula. We also lay down the protocol to
      manage such patients based on our institutional recommendations. 

PMID- 25866558
TI  - Facilitating support groups for siblings of children with neurodevelopmental
      disorders using audio-conferencing: a longitudinal feasibility study.
AB  - BACKGROUND: Siblings of children with chronic illness and disabilities are at
      increased risk of negative psychological effects. Support groups enable them to
      access psycho-education and social support. Barriers to this can include the
      distance they have to travel to meet face-to-face. Audio-conferencing, whereby
      three or more people can connect by telephone in different locations, is an
      efficient means of groups meeting and warrants exploration in this healthcare
      context. This study explored the feasibility of audio-conferencing as a method of
      facilitating sibling support groups. METHODS: A longitudinal design was adopted.
      Participants were six siblings (aged eight to thirteen years) and parents of
      children with complex neurodevelopmental disorders attending the Centre for
      Interventional Paediatric Psychopharmacology (CIPP). Four of the eight one-hour
      weekly sessions were held face-to-face and the other four using audio
      conferencing. Pre- and post-intervention questionnaires and interviews were
      completed and three to six month follow-up interviews were carried out. The
      sessions were audio-recorded, transcribed and thematic analysis was undertaken.
      RESULTS: Audio-conferencing as a form of telemedicine was acceptable to all six
      participants and was effective in facilitating sibling support groups. Audio
      conferencing can overcome geographical barriers to children being able to receive
      group therapeutic healthcare interventions such as social support and psycho
      education. Psychopathology ratings increased post-intervention in some
      participants. Siblings reported that communication between siblings and their
      family members increased and siblings' social network widened. CONCLUSIONS: Audio
      conferencing is an acceptable, feasible and effective method of facilitating
      sibling support groups. Siblings' clear accounts of neuropsychiatric symptoms
      render them reliable informants. Systematic assessment of siblings' needs and
      strengthened links between Child and Adolescent Mental Health Services, school
      counsellors and young carers groups are warranted.

PMID- 25866559
TI  - Comment: Affect Control Theory and Cultural Priming: A Perspective from Cultural
      Neuroscience.
AB  - Affect control theory posits that emotions are constructed by social and cultural
      forces. Rogers, Schroder, and von Scheve (2014) introduce affect control theory
      as a conceptual and methodological "hub," linking theories from different
      disciplines across levels of analysis. To illustrate this further, we apply their
      framework to cultural priming, an experimental technique in cultural psychology
      and neuroscience for testing how exposure to cultural symbols (e.g., words and
      pictures) changes people's behavior, cognition, and emotion. Our analysis
      supports the use of affect control theory in linking different levels of analysis
      while leaving some opening questions for improving such a framework in future
      research.

PMID- 25866560
TI  - Recent advances in 3D printing of biomaterials.
AB  - 3D Printing promises to produce complex biomedical devices according to computer
      design using patient-specific anatomical data. Since its initial use as pre
      surgical visualization models and tooling molds, 3D Printing has slowly evolved
      to create one-of-a-kind devices, implants, scaffolds for tissue engineering,
      diagnostic platforms, and drug delivery systems. Fueled by the recent explosion
      in public interest and access to affordable printers, there is renewed interest
      to combine stem cells with custom 3D scaffolds for personalized regenerative
      medicine. Before 3D Printing can be used routinely for the regeneration of
      complex tissues (e.g. bone, cartilage, muscles, vessels, nerves in the
      craniomaxillofacial complex), and complex organs with intricate 3D
      microarchitecture (e.g. liver, lymphoid organs), several technological
      limitations must be addressed. In this review, the major materials and technology
      advances within the last five years for each of the common 3D Printing
      technologies (Three Dimensional Printing, Fused Deposition Modeling, Selective
      Laser Sintering, Stereolithography, and 3D Plotting/Direct-Write/Bioprinting) are
      described. Examples are highlighted to illustrate progress of each technology in
      tissue engineering, and key limitations are identified to motivate future
      research and advance this fascinating field of advanced manufacturing. 

PMID- 25866561
TI  - Deconstructing the genetic basis of spent sulphite liquor tolerance using deep
      sequencing of genome-shuffled yeast.
AB  - BACKGROUND: Identifying the genetic basis of complex microbial phenotypes is
      currently a major barrier to our understanding of multigenic traits and our
      ability to rationally design biocatalysts with highly specific attributes for the
      biotechnology industry. Here, we demonstrate that strain evolution by meiotic
      recombination-based genome shuffling coupled with deep sequencing can be used to
      deconstruct complex phenotypes and explore the nature of multigenic traits, while
      providing concrete targets for strain development. RESULTS: We determined genomic
      variations found within Saccharomyces cerevisiae previously evolved in our
      laboratory by genome shuffling for tolerance to spent sulphite liquor. The
      representation of these variations was backtracked through parental mutant pools
      and cross-referenced with RNA-seq gene expression analysis to elucidate the
      importance of single mutations and key biological processes that play a role in
      our trait of interest. Our findings pinpoint novel genes and biological
      determinants of lignocellulosic hydrolysate inhibitor tolerance in yeast. These
      include the following: protein homeostasis constituents, including Ubp7p and
      Art5p, related to ubiquitin-mediated proteolysis; stress response transcriptional
      repressor, Nrg1p; and NADPH-dependent glutamate dehydrogenase, Gdh1p. Reverse
      engineering a prominent mutation in ubiquitin-specific protease gene UBP7 in a
      laboratory S. cerevisiae strain effectively increased spent sulphite liquor
      tolerance. CONCLUSIONS: This study advances understanding of yeast tolerance
      mechanisms to inhibitory substrates and biocatalyst design for a biomass-to
      biofuel/biochemical industry, while providing insights into the process of
      mutation accumulation that occurs during genome shuffling.

PMID- 25866562
TI  - Uniconazole-induced starch accumulation in the bioenergy crop duckweed (Landoltia
      punctata) I: transcriptome analysis of the effects of uniconazole on chlorophyll
      and endogenous hormone biosynthesis.
AB  - BACKGROUND: Duckweed is a novel aquatic bioenergy crop that is found ubiquitously
      throughout the world. Uniconazole plays an important role in improving crop
      production through the regulation of endogenous hormone levels. We found that a
      high quantity and quality of duckweed growth can be achieved by uniconazole
      application, although the mechanisms are unknown. RESULTS: The fronds of
      Landoltia punctata were sprayed evenly with 800 mg/L uniconazole. The dry weight
      following treatment increased by 10% compared to the controls at 240 h.
      Endogenous cytokinin (CK) and abscisic acid (ABA) content both increased compared
      to the control, while the level of gibberellins (GAs) decreased. Additionally,
      gene expression profiling results showed that the expression of transcripts
      encoding key enzymes involved in endogenous CK and ABA biosynthesis were up
      regulated, while the transcripts of key enzymes for GAs biosynthesis were down
      regulated. On the other hand, chlorophyll a and chlorophyll b contents were both
      increased compared with the control. Moreover, the net photosynthetic rate was
      elevated to 25.6 MUmol CO2/m(2)/s compared with the control value of 22.05 MUmol
      CO2/m(2)/s. Importantly, the expression of some chlorophyll biosynthesis-related
      transcripts was up-regulated. CONCLUSION: Uniconazole treatment altered
      endogenous hormone levels and enhanced chlorophyll content and net photosynthetic
      rate in duckweed by regulating key enzymes involved in endogenous hormone and
      chlorophyll biosynthesis. The alterations of endogenous hormones and the increase
      of chlorophyll and photosynthetic rate data support the increase of biomass and
      starch accumulation.

PMID- 25866563
TI  - A microbial platform for renewable propane synthesis based on a fermentative
      butanol pathway.
AB  - BACKGROUND: Propane (C3H8) is a volatile hydrocarbon with highly favourable
      physicochemical properties as a fuel, in addition to existing global markets and
      infrastructure for storage, distribution and utilization in a wide range of
      applications. Consequently, propane is an attractive target product in research
      aimed at developing new renewable alternatives to complement currently used
      petroleum-derived fuels. This study focuses on the construction and evaluation of
      alternative microbial biosynthetic pathways for the production of renewable
      propane. The new pathways utilize CoA intermediates that are derived from
      clostridial-like fermentative butanol pathways and are therefore distinct from
      the first microbial propane pathways recently engineered in Escherichia coli.
      RESULTS: We report the assembly and evaluation of four different synthetic
      pathways for the production of propane and butanol, designated a) atoB-adhE2
      route, b) atoB-TPC7 route, c) nphT7-adhE2 route and d) nphT7-TPC7 route. The
      highest butanol titres were achieved with the atoB-adhE2 (473 +/- 3 mg/L) and
      atoB-TPC7 (163 +/- 2 mg/L) routes. When aldehyde deformylating oxygenase (ADO)
      was co-expressed with these pathways, the engineered hosts also produced propane.
      The atoB-TPC7-ADO pathway was the most effective in producing propane (220 +/- 3
      MUg/L). By (i) deleting competing pathways, (ii) including a previously designed
      ADOA134F variant with an enhanced specificity towards short-chain substrates and
      (iii) including a ferredoxin-based electron supply system, the propane titre was
      increased (3.40 +/- 0.19 mg/L). CONCLUSIONS: This study expands the metabolic
      toolbox for renewable propane production and provides new insight and
      understanding for the development of next-generation biofuel platforms. In
      developing an alternative CoA-dependent fermentative butanol pathway, which
      includes an engineered ADO variant (ADOA134F), the study addresses known
      limitations, including the low bio-availability of butyraldehyde precursors and
      poor activity of ADO with butyraldehyde. Graphical abstractPropane synthesis
      derived from a fermentative butanol pathway is enabled by metabolic engineering.

PMID- 25866564
TI  - Atom-Atom-Path similarity and Sphere Exclusion clustering: tools for prioritizing
      fragment hits.
AB  - BACKGROUND: After performing a fragment based screen the resulting hits need to
      be prioritized for follow-up structure elucidation and chemistry. This paper
      describes a new similarity metric, Atom-Atom-Path (AAP) similarity that is used
      in conjunction with the Directed Sphere Exclusion (DISE) clustering method to
      effectively organize and prioritize the fragment hits. The AAP similarity rewards
      common substructures and recognizes minimal structure differences. The DISE
      method is order-dependent and can be used to enrich fragments with properties of
      interest in the first clusters. RESULTS: The merit of the software is
      demonstrated by its application to the MAP4K4 fragment screening hits using
      ligand efficiency (LE) as quality measure. The first clusters contain the hits
      with the highest LE. The clustering results can be easily visualized in a LE-over
      clusters scatterplot with points colored by the members' similarity to the
      corresponding cluster seed. The scatterplot enables the extraction of preliminary
      SAR. CONCLUSIONS: The detailed structure differentiation of the AAP similarity
      metric is ideal for fragment-sized molecules. The order-dependent nature of the
      DISE clustering method results in clusters ordered by a property of interest to
      the teams. The combination of both allows for efficient prioritization of
      fragment hit for follow-ups. Graphical abstractAAP similarity computation and
      DISE clustering visualization.

PMID- 25866565
TI  - Considerations regarding current diagnosis and prognosis of hepatocellular
      carcinoma.
AB  - Hepatocellular carcinoma is a major health issue, ranked the fifth most common
      tumor and currently being responsible for a third of the cancer-related deaths
      globally, with an ever-increasing number of fatalities. Current advances in
      contrast-enhanced imaging techniques such as contrast-enhanced ultrasonography,
      multi-detector computed tomography and diffusion-weighted magnetic resonance
      imaging are improving the rate of hepatocellular carcinoma diagnosis. Contrast
      enhanced ultrasonography has widely become the first choice in liver tumor
      assessment, as it is faster, simpler and safer than other forms of diagnostic
      imaging. On the other hand, cross sectional computed tomography is frequently
      employed when a hepatic formation is suspected of malignancy and allows a more
      accurate characterization of lesions through multiphasic multi-detector computed
      tomography technology. Diffusion weighted magnetic resonance imaging represents
      another addition to the wide range of diagnostic and prognostic techniques
      available for patients with hepatocellular carcinoma and is currently regarded as
      one of the best tools for the characterization of these lesions. Furthermore,
      groundbreaking biomarkers for hepatocellular carcinoma are being discovered,
      although alpha-fetoprotein remains one of the most frequently used serum test in
      the early stages. Nonetheless, further advances are required for the detection of
      small liver carcinomas.

PMID- 25866566
TI  - Fallopian tubes--literature review of anatomy and etiology in female infertility.
AB  - RATIONALE: Around 30% of the infertile women worldwide have associated Fallopian
      tubes pathology. Unfortunately, for a long time, this aspect of infertility has
      been neglected due to the possibility of bypassing this deadlock through IVF.
      OBJECTIVE: Up to date free full text literature was reviewed, meaning 4 major
      textbooks and around 100 articles centered on tubal infertility, in order to
      raise the awareness on this subject. METHODS AND RESULTS: The anatomy of the
      Fallopian tube is complex starting from its embryological development and
      continuing with its vascular supply and ciliated microstructure, that is the key
      to the process of egg transport to the site of fertilization. There are many
      strongly documented causes of tubal infertility: infections (Chlamydia
      Trachomatis, Gonorrhea, and genital tuberculosis), intrauterine contraceptive
      devices, endometriosis, and complications after abdominal surgery, etc.
      DISCUSSIONS: Although there are still many controversies about the etiology of
      tubal sterility with the advent of molecular diagnosis of infections there has
      been cleared the pathway of infection through endometriosis or through ciliary
      immobility towards the tubal obstruction.

PMID- 25866567
TI  - Controversies in the diagnosis and treatment of early cutaneous melanoma.
AB  - Cutaneous melanoma (CM) is a disease with an unpredictable evolution mainly due
      to its high metastatic ability. The steadily increasing incidence and the poor
      outcome in advanced stages made this cancer an interesting field for many
      research groups. Given that CM is a curable disease in early stages, efforts have
      been made to detect it as soon as possible, which led to the diversification and
      refining of diagnosis methods and therapies. But, as the data from trials have
      been published, doubts about the indications and efficacy of established
      treatments have arisen. In fact, there is probably no single aspect of early CM
      that has not given birth to controversy. This article intends to present the
      current disputes regarding the early detection, diagnosis, treatment and
      postoperative follow-up of patients with localized CM. After analyzing both pros
      and cons, several conclusions were drawn, that reflect our experience in managing
      patients with early CM. 

PMID- 25866568
TI  - The polycystic ovary syndrome: an update on metabolic and hormonal mechanisms.
AB  - Polycystic ovary syndrome (PCOs) is a public health important disease, affecting
      one in five women at reproductive age. The clinical implications include
      reproductive, metabolic and psychological features. This article reviews the
      literature data related to the new metabolic and hormonal mechanisms in PCOs.
      Recognizing the real diagnostic of PCOs, using the right criteria, is a challenge
      in current practice. 

PMID- 25866569
TI  - Pelvic exenteration--reconsidering the procedure.
AB  - Pelvic exenteration remains one of the most destructive surgical procedures in
      gynecologic oncology, performed in patients with locally advanced malignancies
      who were considered for a long time as unresectable. However, for these patients,
      an aggressive surgical approach seems to be the only potential curative solution.
      This is a literature review of the most important studies, which analyzes the
      benefits and the secondary risks of this demanding procedure. 

PMID- 25866570
TI  - Current endoscopic methods of radical therapy in early esophageal cancer.
AB  - During the last three decades, there has been an increasing incidence of the
      esophageal cancer at the global level, approx. 400,000 new esophageal cancers
      being currently diagnosed annually. This is the eighth leading cause of cancer
      incidence and the sixth leading cause of cancer death overall. If we refer to the
      countries of Western Europe and North America, we could see an increase in the
      esophageal adenocarcinoma in detriment of squamous cancer. As for the Asian
      region, referring in particular to China and Japan, 9 out of 10 esophageal
      cancers are squamous cell carcinomas. Considering that the incidence of gastric
      cancer in Japan is very high, the endoscopic screenings performed inevitably led
      to an increased rate of early detection of esophageal cancer, reaching
      approximately 20% of all esophageal cancers detected. This has led to the
      possibility of developing therapeutic endoscopic techniques with radical visa
      that we will describe while presenting comparative data from literature.
      Currently, however, there are not enough data on the effectiveness of these types
      of therapies, compared to surgery, in order to be transformed into standard
      therapeutic endoscopic treatment for early esophageal cancer. However, the
      combined therapy, resection/ endoscopic ablation + chemoradiotherapy, appears as
      an alternative to be taken into account. Abbreviations EEC = esophageal early
      cancer, BE = Barrett's esophagus, HGD = High-grade dysphagia, EUS = Ultra sound
      endoscopy, CT = Computer tomograph, UGE = Upper gastro endoscopy, PET-CT =
      Positron Emission Tomography, FNAB = Fine needle aspiration biopsy, EMR =
      Esophageal mucosal resection, ESD = Esophageal submucosal dissection, SCC =
      Squamous cellular cancer, PCT = Poli-chemotherapy, RT- Radio-therapy. 

PMID- 25866571
TI  - Current management of tubal infertility: from hysterosalpingography to
      ultrasonography and surgery.
AB  - RATIONALE: The development of IVF techniques has diminished the importance of
      tubal infertility but recent discoveries shed a new light on reproductive tubal
      surgery prior to any IVF cycle. OBJECTIVE: To adapt current state of the art
      recommendations concerning tubal factor infertility to actual possibilities in
      Romanian healthcare system and to grow the awareness of fellow fertility
      specialists and general practitioners to the improved outcomes of novel
      management and treatment modalities. METHODS AND RESULTS: 67 free full text
      articles centered on the subject of management in tubal infertility were
      identified in international databases. Four articles described general diagnosis
      using data from medical history, 21 works approached the diagnosis through
      hysterosalpingography, 14 papers introduced the use of different sonographic
      procedures, 8 files analyzed the importance of exploratory laparoscopy and 20
      articles reviewed different treatment modalities. DISCUSSIONS: Current data show
      that active implementation of the large scale use of tubal surgery prior to any
      IVF cycle will reduce up to 30% the costs associated with obtaining a viable
      pregnancy in cases with tubal factor sterility.

PMID- 25866572
TI  - Burnei's anterior transthoracic retropleural approach of the thoracic spine: a
      new operative technique in the treatment of spinal disorders.
AB  - BACKGROUND: Up to the middle of the last century, the thoracic spine, especially
      in its upper part, has been considered an unapproachable site, a no-man's land,
      but the constant evolution of medicine imposed techniques of the spine at these
      levels in order to solve a large area of pathology (infectious, tumoral,
      traumatic, and last but not least, deformative). This way, a series of anterior
      approaches allowed surgeons to gain access to the anterior part of the spine and
      the posterior mediastinum. The approaches described by Hodgson, Mirbaha or
      transthoracic transpleural approach (T4-T11), are enumerated. The idea to allow a
      more visible and extensive approach, but to avoid respiratory issues due to the
      lesion of the pleura, led to the description of a new anterior approach by Burnei
      in 2000. MATERIAL AND METHOD: Burnei's approach represents an anterior approach
      to the thoracic spine, being a transthoracic and retropleural one. This approach
      allows a large area of spinal pathology due to infectious, traumatic, tumoral and
      degenerative (idiopathic or congenital scoliosis) causes. Statistically, this
      approach has been performed more frequently in cases of spinal instrumentation
      after diskectomy, in order to perform a partial correction of severe, rigid
      idiopathic scoliosis with more than 70 degrees Cobb and in cases of congenital
      scoliosis for hemivertebra resection and somatic synthesis to correct the
      scoliotic curve. RESULTS: This kind of anterior approach allows the surgeon a
      large visibility of the anterior thoracic spine, diskectomies of up to 5 levels
      to tender the curve of the deformity and to ensure somatic or/ and transpedicular
      synthesis of up to 6 thoracic vertebrae. By performing a thoracotomy involving
      the resection of the posterior arches of the ribs, a thoracoplasty is also
      ensured with functional and aesthetic effects, by ameliorating the thoracic hump
      due to the scoliotic deformity. CONCLUSIONS: Burnei's approach joins all the
      other anterior approaches of the spine, addressing a large area of pathology of
      the thoracic spine. Even if difficult to be performed, requiring a thorough and
      perfect technique in the hands of a skilled surgeon, it will ensure satisfaction
      due to the detailed and visible exposure of the thoracic spine.

PMID- 25866573
TI  - Improving the quality of Health Care in the Romanian public health system--a
      priority in the reform process.
AB  - To meet the shortfalls caused by the economic crisis, the Romanian medical system
      needed an objective analysis of the quality of medical care as a whole, of the
      entire package of health services as well as accountable joint efforts to
      identify system problems and, especially, firm action without compromising
      resolution, regardless of any limitations or emotional picture. In addition, last
      but not least, the judicious use of available resources. 

PMID- 25866574
TI  - Pharmacogenetics aspects of oral anticoagulants therapy.
AB  - RATIONALE: Vitamin K antagonists (VKA), such as warfarin and acenocoumarol, are
      widely used for the prevention and treatment of thromboembolic diseases and they
      are some of the most commonly prescribed types of medications. They are
      characterized by narrow therapeutic indices and inter-individual or intra
      individual variability in response to the treatment. OBJECTIVE: to establish the
      influence of several genetic factors on VKA efficacy and adverse reactions.
      METHODS AND RESULTS: The metabolism of VKA differs depending on their chemical
      structure: indandiones derivatives (fluindione) or coumarin derivatives
      (acenocoumarol, phenprocoumon or warfarin). They are mostly metabolized in
      hepatocytes via a monooxygenase, cytochrome P450 2C9 (CYP2C9), resulting in
      inactive products. The gene encoding CYP2C9 is polymorphic, its genetic variants
      being associated with differences in the enzymatic activity of CYP2C9. The most
      important in terms of their frequency in the general population are CYP2C9*2 and
      CYP2C9*3. Both alleles are associated with a marked decrease in CYP2C9 enzyme
      activity. VK epoxide reductase (VKOR) is an enzyme with an important role in VK
      metabolism. Various polymorphisms in the VKORC1 gene have been described.
      VKORC1*2 haplotype seems to be the most important in relation to the variability
      in response to VKA. DISCUSSIONS: Various studies have shown a relationship
      between the genotype and the mean warfarin maintenance dosing: in patients
      carrying 2C9*1/*2 alleles, the dose is reduced by 18-40% in patients carrying
      2C9*2/*2 alleles, by 21-49% in patients carrying 2C9*1/*3 alleles. The A allele
      of the c.-1639G>A polymorphism in the VKORC1 gene is associated with the need for
      a lower dose of acenocoumarol in patients on anticoagulant therapy.
      ABBREVIATIONS: SNP = Single Nucleotide Polymorphism, VKA = vitamin K antagonists,
      C1 - VKORC1 = vitamin K epoxide reductase complex subunit, INR = International
      Normalized Ratio.

PMID- 25866575
TI  - Sentinel lymph node biopsy (SLNB) vs. axillary lymph node dissection (ALND) in
      the current surgical treatment of early stage breast cancer.
AB  - The identification and biopsy of the sentinel lymph node has become a standard
      method of treatment for stage I and II breast cancer in the last decades, taking
      into account the fact that the management of the axilla in patients with breast
      cancer has evolved from the routine lymphadenectomy to a selective attitude,
      based on the histopathological evaluation of the sentinel lymph node, as well as
      on the tumor and on the patients' characteristics. Since the introduction of the
      method into clinical practice, in 1994, different methods of identification have
      been used (radioisotope injection, vital blue dye, or, more recently, lipophilic
      contrast agent for ultrasound visualization or paramagnetic nanoparticles (NPs)
      or the method of indocyanine green fluorescence), each presenting certain limits,
      but the radioisotopic method proving the most accurate. Moreover, during the
      development of the method, beside the standard indications specific for T1 or T2
      breast tumor, without clinical or imagistic axillary adenopathies, their
      extension to a series of other particular situations such as the following, has
      been tried: ductal carcinoma in situ, multicentre tumors, after excisional biopsy
      or tumors preoperatively treated by neoadjuvant chemotherapy. The aim of the
      paper is to present the progress made regarding the current stage in the use of
      sentinel lymph node technique in breast cancer, while mentioning the established
      indications, as well as the ones that are still debating and need further
      studies. Likewise, the cases in which the axillary lymph node dissection remains
      the major indication for treatment of the axilla, in patients with early stage
      breast cancer, will be discussed. 

PMID- 25866576
TI  - Current challenges and pitfalls in the pharmacological treatment of depression.
AB  - The multifactorial etiology of depression obliges needs an individual assessment,
      the psychopharmacological approach involving a biopsychosocial analysis for each
      individual case. The rebalancing of the depressive patient, seen as a return to a
      normal level of psychosocial functioning and reduced risk of relapse is achieved
      with a prompt and constant support of specialized teams. Treatment should include
      psychopharmacological and psychosocial approaches, the results being interrelated
      and contributing to the prognosis of the disorder. Progress in clinical and
      pharmacological research, vivid dynamics of socio-economic environment, the
      complexity of diagnostic evaluation and the need for an interdisciplinary
      approach may cause difficulties in addressing the depressive patient and the
      ethical controversies. The aim of this paper is to present a brief analysis of
      challenges encountered in the present psychiatric practice, starting from the
      heterogeneity of depressive manifestations and finishing with the prioritization
      of interventional forms. 

PMID- 25866577
TI  - Metformin-clinical pharmacology in PCOs.
AB  - Oligo-anovulation, hyperandrogenism and insulin resistance characterizes
      polycystic ovary syndrome (PCOs). Metformin is the oldest insulin sensitizer used
      in the management of type 2 diabetes mellitus. In PCOs, metformin decreases the
      serum lipids, androgen and insulin; induces ovulation and regular menstrual
      cycle; increases the pregnancy rate. 

PMID- 25866578
TI  - Endoscopic palliation of advanced esophageal cancer.
AB  - Esophageal cancer represents one of the most aggressive digestive tumors, with a
      survival rate at 5 years of only 10%. Globally, during the last three decades,
      there has been an increasing incidence of the esophageal cancer, approx. 400,000
      new esophageal cancers being currently diagnosed annually. This represents the
      eighth leading cause of cancer incidence and the sixth leading cause of cancer
      death overall. Taking into account the population's global aging and thus, the
      increase in the number of patients who will not bear surgery, PCT and radiation,
      or the fact that they do not want it especially because of deficiencies and
      associated pathology, the endoscopic ablative techniques with palliation purposes
      represent the alternative. If we refer to the Western Europe countries and North
      America, we notice an increase of esophageal adenocarcinoma rate versus squamous
      cancer. As for the Asian region, referring in particular to China and Japan, 9
      out of 10 esophageal cancers are squamous cell carcinomas. For at least half of
      the patients with EC (esophageal cancer) there is no hope of healing because of
      the advanced regional malignant invasion (T3-4, N+, M+) with no chemo and
      radiotherapy response, poor preoperative patients' conditions or systemic
      metastasis. The low life expectancy does not justify the risky medical
      procedures, the goal of the therapy consisting in the improvement of the quality
      of life by eliminating dysphagia (reestablishing oral feeding) which represents
      the most common complication of EC, the respiratory tract complication caused by
      eso-tracheal fistulas or by eliminating chest pain. To treat dysphagia, which is
      the main target of palliation, combined methods like endoscopic, chemo and radio
      therapy, can be used, each one with indications, benefits and risks.

PMID- 25866579
TI  - Impact of maternal melatonin suppression on forced swim and tail suspension
      behavioral despair tests in adult offspring.
AB  - Melatonin is an essential hormone, which regulates circadian rhythms and has
      antioxidative and anticarcinogenic effects. As melatonin secretion is suppressed
      by light, this effect was examined on the offspring of the Wistar rat females
      exposed to continuous light (500 lux) during the second half of the pregnancy
      (day 12 to 21). Control rats were kept under a 12:12 light-dark cycle. The
      resulted male offspring have been behaviorally assessed for depression after
      postnatal day 60 by using Forced Swim Test (FST) and Tail Suspension Test (TST).
      Animals resulted from the melatonin deprived pregnancies have developed an
      abnormal response in the TST, but a normal FST behavior. Also, TST active
      movement was different in the melatonin suppression group compared to the control
      group. These findings suggest that intrauterine melatonin deprivation might be
      linked to the depressive like behavior in adult male offspring. 

PMID- 25866580
TI  - Long-term treatment of aged Long Evans rats with a dietary supplement containing
      neuroprotective peptides (N-PEP-12) to prevent brain aging: effects of three
      months daily treatment by oral gavage.
AB  - Aging is associated with morphological and functional changes in the brain,
      resulting in the deterioration of cognitive performance. Growth factors like BDNF
      are suggested to be involved in the regulation of age-related processes in the
      brain. A novel dietary supplement produced from purified nerve cell proteins, N
      PEP-12, has shown to share properties with naturally occurring peptide growth
      factors by stimulating neurite outgrowth and beneficial effects on neuronal
      survival and protection against metabolic stress in cell cultures. The current
      study investigates the effects of long-term intake on age-dependent memory
      decline by assessing cognitive performance and synaptic density. All the
      experiments were performed in aged Long Evans rats randomly assigned to saline or
      N-PEP-12 once daily by gavage over a period of three months. Behavioral tests
      were performed in the Morris Water Maze after one, two and three months of
      treatment. Histological examinations were performed in the hippocampal formation
      and in the entorhinal cortex by measuring the synaptic density. This study shows
      that the oral intake of N-PEP-12 has beneficial effects on the cognitive
      performance of aged animals and that these effects go along with an increase in
      the synaptic density. Thus, N-PEP-12 may help maintain memory and learning
      performance during the aging process. 

PMID- 25866581
TI  - Limb-sparing surgery as an alternative for limb amputation in an invasive myxoid
      liposarcoma--case report.
AB  - In medical practice, plastic surgeons confront with patients with sarcomas of the
      extremities that require a radical surgical approach. Knowing when to attempt
      limb-sparing surgery and when to give in to limb amputation is one of the most
      difficult decisions a surgeon can take. The correct approach and management of
      such cases ensure surgical success and the patient survival. In this paper, the
      case of a 56-year-old man, admitted in our clinic with a crush injury of the
      right calf and subsequent haematoma is presented. During haematoma drainage, the
      surgeon noticed abnormal tissue and performed an incisional biopsy. The patient
      was diagnosed with myxoid liposarcoma of the external compartment of the right
      calf. Limb amputation was proposed, but the patient refused. After the clinical
      examination, blood tests and diagnostic imaging, which allowed the correct
      evaluation of the case-tumor sizes and neighboring tissue reports, and
      preoperatory radiotherapy, limb sparing surgery, respectively primary tumor
      excision was decided to be performed. Negative margins could not be obtained by 3
      successive resections or by adjuvant chemotherapy. The presented case supports
      the idea that limb-sparing surgery is only applicable to carefully selected
      patients with soft tissue sarcoma. In some cases, radical excision involving even
      mutilating amputations may provide a better oncologic and functional result.

PMID- 25866582
TI  - Evaluation of endometrial cancer epidemiology in Romania.
AB  - Endometrial cancer represents the most frequent gynecological malignant affection
      in the developed countries, in which the incidence of cervical cancer has
      significantly decreased due to the rigorous application of screening methods and
      prophylaxis. According to its frequency, endometrial cancer is situated on the
      fourth place in the category of women's genital-mammary malignant diseases, after
      breast, cervical and ovarian cancer in Romania. The incidence and mortality rates
      due to endometrial cancer have registered an increasing trend worldwide and also
      in Romania, a significant decrease of the age of appearance for the entire
      endometrial pathology sphere being noticed. At the national level, the maximum
      incidence is situated between 60 and 64 years old, the mortality rate of the
      women under 65 years old being high in Romania. The study evaluates endometrial
      cancer, from an epidemiologic point of view, at the national level compared to
      the international statistic data. 

PMID- 25866583
TI  - CT vs. MRCP in choledocholithiasis jaundice.
AB  - RATIONALE: Obstructive jaundice can raise problems to diagnostic imaging. The
      radiologist must choose the most appropriate examination that delivers the most
      important diagnostic information because the differences between a lithiasic
      obstruction and a tumoral one are vital. This information helps the surgeon speed
      up the process of decision-making, because the treatment may be very different in
      relation to the nature of the obstruction. OBJECTIVE: This study tries to
      demonstrate the diagnostic accuracy of computed tomography (CT) and magnetic
      resonance cholangiopancreatography (MRCP) in detecting the obstacle in the common
      bile duct (CBD) and the possibility of establishing the lithiasic nature of the
      obstruction. METHODS AND RESULTS: A retrospective analysis was analyzed during an
      interval of 18 months that included jaundice patients admitted in the General
      Surgery Department of "Coltea" Clinical Hospital. They were examined by CT
      scanning and by MRCP, being suspected of choledocholithiasis. 63 patients were
      included in the study, 34 females and 29 males. 33 CT scans and 30 MRCP exams
      were performed. DISCUSSION: CT scan is useful in detecting residual or iterative
      choledocholithiasis in patients after cholecystectomy, contrast enhanced CT
      (CECT), being able to differentiate between lithiasic and non-lithiasic
      obstruction. MRCP delivers important anatomic details of the biliary tree; it is
      superior to CT in diagnosing the hepatocholedochal lithiasis; MRCP tends to
      replace endoscopic retrograde cholangiopancreatography (ERCP)--the diagnostic
      "gold standard" reducing the number of unnecessary invasive diagnostic
      procedures.

PMID- 25866584
TI  - The study of the rs9939609 FTO gene polymorphism in association with obesity and
      the management of obesity in a Romanian cohort.
AB  - The incidence of obesity especially in Romanian population is presently
      escalating as a major nutrition and health problem. Clinicians aided by
      scientists are engaged in research approaches that include heredity aspects
      linked with behavior, education, applied nutrition studies and clinical therapies
      in order to prevent, control and reverse obesity. The common goal is to identify
      areas of basic and clinical research to understand aspects of human biology that
      may be considered as obesogenic. Regarding these approaches, recent discoveries
      in genetics, epigenetics and functional genomics, based on advancing
      technologies, are tools employed to prevent and treat obesity. The purpose of
      this article is to present the current knowledge of key components of the FTO
      gene role in the obesogenic system that links genetic, epigenetic and
      environmental, lifestyle/ diet nutritional and behavioral components and to
      describe the results obtained by genotyping and interviewing relevant selected
      groups of Romanian population. FTO rs9939609 genotyping was performed on a
      Romanian study group of 53 subjects (30 obese, 23 normal). Results have been
      analyzed in association with obesity parameters and comorbidities in order to
      identify this polymorphism's effect on body mass in our Caucasian cohort. At the
      same time, personal history of the subjects in correlation with the FTO genotypes
      provided important information on the FTO gene's influence on the feeding
      behavior and food selection of these individuals. In conclusion, the FTO
      rs9939609 polymorphism has been identified as a common gene variant in our
      Romanian Caucasian cohort, proving a high association with all the parameters of
      obesity and obesity comorbidities. The adherence to a Mediterranean diet is
      benefic for subjects with genetic predisposition for this disorder as long as it
      is kept for a long period of time along with sustained physical exercise.
      Association studies are an extremely important tool in understanding the hunger
      satiety pathway, providing information on the relation between obesity-related
      genes, gene expression and behavior. 

PMID- 25866585
TI  - Burnei-Gavriliu classification of congenital scoliosis.
AB  - INTRODUCTION: The existent classifications of congenital scoliosis cannot contain
      all the cases encountered in the medical practice taking into account the
      complexity of the spine deformity in this pathology. PURPOSE: The paper
      represents a retrospective study that analyses a new classification of congenital
      scoliosis in comparison with the existing classification. MATERIALS AND METHOD:
      This study analyses 56 cases over a period of 14 years (2000-2013), based on the
      spine dominant deviation: longitudinal or rotational imbalance. RESULTS: This new
      classification contains not only the formation, segmentation and mixed defects,
      but also the formation failure with or without fusion failure of the ossification
      centers (wedged vertebra, hemivertebral body, segmented, hemisegmented,
      unsegmented hemivertebra, which may be successive, intermittent, alternant
      compensated or alternant decompensated). It also contains the congenital
      scoliosis with a rotational imbalance by spinal traction, spinal pushing or by a
      mixed effect. DISCUSSION: In comparison with the other classifications in
      literature: Winter, Imagama or Kawakami, this classification systematizes data
      according not only to the spatial disposition of the hemivertebrae, but also to
      the balance of the deformity. CONCLUSIONS: In conclusion, this classification of
      congenital scoliosis has a practical, diagnostic, therapeutical and prognostic
      use.

PMID- 25866586
TI  - Gastrointestinal stem cell up-to-date.
AB  - Cellular and tissue regeneration in the gastrointestinal tract depends on stem
      cells with properties of self-renewal, clonogenicity, and multipotency. Progress
      in stem cell research and the identification of potential gastric, intestinal,
      colonic stem cells new markers and the signaling pathways provide hope for the
      use of stem cells in regenerative medicine and treatments for disease. This
      review provides an overview of the different types of stem cells, focusing on
      tissue-restricted adult stem cells. 

PMID- 25866587
TI  - Graph-regularized 3D shape reconstruction from highly anisotropic and noisy
      images.
AB  - Analysis of microscopy images can provide insight into many biological processes.
      One particularly challenging problem is cellular nuclear segmentation in highly
      anisotropic and noisy 3D image data. Manually localizing and segmenting each and
      every cellular nucleus is very time-consuming, which remains a bottleneck in
      large-scale biological experiments. In this work, we present a tool for automated
      segmentation of cellular nuclei from 3D fluorescent microscopic data. Our tool is
      based on state-of-the-art image processing and machine learning techniques and
      provides a user-friendly graphical user interface. We show that our tool is as
      accurate as manual annotation and greatly reduces the time for the registration.

PMID- 25866588
TI  - Fiber optical parametric amplifiers in optical communication systems.
AB  - The prospects for using fiber optical parametric amplifiers (OPAs) in optical
      communication systems are reviewed. Phase-insensitive amplifiers (PIAs) and phase
      sensitive amplifiers (PSAs) are considered. Low-penalty amplification at/or near
      1 Tb/s has been achieved, for both wavelength- and time-division multiplexed
      formats. High-quality mid-span spectral inversion has been demonstrated at 0.64
      Tb/s, avoiding electronic dispersion compensation. All-optical amplitude
      regeneration of amplitude-modulated signals has been performed, while PSAs have
      been used to demonstrate phase regeneration of phase-modulated signals. A PSA
      with 1.1-dB noise figure has been demonstrated, and preliminary wavelength
      division multiplexing experiments have been performed with PSAs. 512 Gb/s have
      been transmitted over 6,000 km by periodic phase conjugation. Simulations
      indicate that PIAs could reach data rate x reach products in excess of 14,000
      Tb/s * km in realistic wavelength-division multiplexed long-haul networks.
      Technical challenges remaining to be addressed in order for fiber OPAs to become
      useful for long-haul communication networks are discussed. [Formula: see text].

PMID- 25866589
TI  - Probing the biophysical properties of primary breast tumor-derived fibroblasts.
AB  - As cancer progresses, cells must adapt to a new and stiffer environment, which
      can ultimately alter how normal cells within the tumor behave. In turn, these
      cells are known to further aid tumor progression. Therefore, there is potentially
      a unique avenue to better understand metastatic potential through single-cell
      biophysical assays performed on patient-derived cells. Here, we perform
      biophysical characterization of primary human fibroblastic cells obtained from
      mammary carcinoma and normal contralateral tissue. Through a series of tissue
      dissociation, differential centrifugation and trypsinization steps, we isolate an
      adherent fibroblastic population viable for biomechanical testing. 2D TFM and 3D
      migration measurements in a collagen matrix show that fibroblasts obtained from
      patient tumors generate more traction forces and display improved migration
      potential than their counterparts from normal tissue. Moreover, through the use
      of an embedded spheroid model, we confirmed the extracellular matrix (ECM)
      remodeling behavior of primary cells isolated from carcinoma. Overall,
      correlating biophysical characterization of normal- and carcinoma-derived samples
      from individual patient along with patient outcome may become a powerful approach
      to further our comprehension of metastasis and ultimately design drug targets on
      a patient-specific basis.

PMID- 25866590
TI  - Genome-wide blood DNA methylation alterations at regulatory elements and
      heterochromatic regions in monozygotic twins discordant for obesity and liver
      fat.
AB  - BACKGROUND: The current epidemic of obesity and associated diseases calls for
      swift actions to better understand the mechanisms by which genetics and
      environmental factors affect metabolic health in humans. Monozygotic (MZ) twin
      pairs showing discordance for obesity suggest that epigenetic influences
      represent one such mechanism. We studied genome-wide leukocyte DNA methylation
      variation in 30 clinically healthy young adult MZ twin pairs discordant for body
      mass index (BMI; average within-pair BMI difference: 5.4 +/- 2.0 kg/m(2)).
      RESULTS: There were no differentially methylated cytosine-guanine (CpG) sites
      between the co-twins discordant for BMI. However, stratification of the twin
      pairs based on the level of liver fat accumulation revealed two epigenetically
      highly different groups. Significant DNA methylation differences (n = 1,236 CpG
      sites (CpGs)) between the co-twins were only observed if the heavier co-twins had
      excessive liver fat (n = 13 twin pairs). This unhealthy pattern of obesity was
      coupled with insulin resistance and low-grade inflammation. The differentially
      methylated CpGs included 23 genes known to be associated with obesity, liver fat,
      type 2 diabetes mellitus (T2DM) and metabolic syndrome, and potential novel
      metabolic genes. Differentially methylated CpG sites were overrepresented at
      promoters, insulators, and heterochromatic and repressed regions. Based on
      predictions by overlapping histone marks, repressed and weakly transcribed sites
      were significantly more often hypomethylated, whereas sites with strong enhancers
      and active promoters were hypermethylated. Further, significant clustering of
      differentially methylated genes in vitamin, amino acid, fatty acid, sulfur, and
      renin-angiotensin metabolism pathways was observed. CONCLUSIONS: The methylome in
      leukocytes is altered in obesity associated with metabolic disturbances, and our
      findings indicate several novel candidate genes and pathways in obesity and
      obesity-related complications.

PMID- 25866591
TI  - Is vitamin d deficiency a new risk factor for cardiovascular disease?
AB  - The role of vitamin D in the regulation of bone metabolism has been well
      established. However, in recent years, many studies have demonstrated that its
      role extends far beyond bone health. Growing evidence has shown a strong
      association between vitamin D deficiency and hypertension, metabolic syndrome,
      diabetes mellitus and atherosclerosis. The mechanisms by which vitamin D exerts
      its cardiovascular protective effects are still not completely understood, but
      there is evidence that it participates in the regulation of renin-angiotensin
      system and the mechanisms of insulin sensitivity and activity of inflammatory
      cytokines, besides its direct cardiovascular actions. In this review, several
      studies linking vitamin D deficiency with cardiometabolic risk as well as small
      randomized trials that have evaluated the cardiovascular effects of its
      supplementation are presented. However, large randomized placebo-controlled
      studies are still needed before we can definitively establish the role of vitamin
      D supplementation in the prevention and control of cardiovascular disease. 

PMID- 25866593
TI  - A Rare Case of Aggressive Fibromatosis Infiltrating Dorsal Muscles in a 6-Year
      Old Patient - CT, MRI and Elastography Evaluation.
AB  - BACKGROUND: The term fibromatosis or desmoid tumor refers to a group of benign
      fibrous growths without metastatic potential but with a significant risk of local
      recurrence. These lesions typically present infiltrative growth pattern with
      local invasion of adjacent tissues. This tendency is the reason for a relatively
      high rate of local recurrence, even after surgical removal. Fibromatosis is a
      very rare condition in general population but occurs more frequently in one of
      the familial cancer predispositions known as familial adenomatous polyposis (FAP)
      or Gardner syndrome. There are two main groups of fibromatosis: superficial
      (small, slow-growing lesions) and deep, also known as aggressive fibromatosis
      (large, rapid-growing lesions). CASE REPORT: We report a case of a 6-year-old boy
      suffering from an aggressive form of fibromatosis. The patient developed a large
      pathological mass extending from the neck to the loins. After incisional biopsy
      and histpoathological examination of the sample, a diagnosis of aggressive
      fibromatosis was established. During the whole diagnostic process, different
      imaging techniques including CT, MRI and sonoelastography were used. As the
      surgical treatment was not possible, the patient was finally qualified for
      chemotherapy. CONCLUSIONS: Eventual diagnosis of aggressive fibromatosis is based
      on histopathological examination. However, it is an important condition that
      should be included in differential diagnosis of soft-tissue masses found in
      diagnostic imaging. Radiologists should be careful especially in defining the
      margins of infiltration in case of potential surgical treatment.

PMID- 25866594
TI  - Fibrolamellar hepatocellular carcinoma presenting as obstructive jaundice:
      uncommon presentation of a rare entity.
AB  - BACKGROUND: Fibrolamellar hepatocellular carcinoma is a rare primary malignant
      liver tumor, significantly different from generic hepatocellular carcinoma with
      distinct demographics, risk factors, imaging features, histopathology and
      prognosis. CASE REPORT: Unlike conventional hepatocellular carcinoma, it presents
      in young individuals with no preexisting hepatitis or cirrhosis and does not
      cause elevation of serum alpha feto proteins in most cases. This paper presents a
      case report of this rare tumor in a young female with an unusual clinical
      manifestation of obstructive jaundice (which has not been reported so far) along
      with a review of its imaging and pathological features, with treatment options.
      CONCLUSIONS: Fibrolamellar HCC is a rare variant of classic HCC with different
      epidemiology, risk factors, clinical manifestations, radiological, pathological
      and prognostic features. Therefore, it is important to be familiar with the
      entity for its early diagnosis and management.

PMID- 25866595
TI  - Hemangioma of rib: a different perspective.
AB  - BACKGROUND: Hemangiomas are one of the common primary benign tumors of the
      intraosseous and soft tissue compartments in humans. Vertebral hemangiomas being
      the most common of all are seen in daily radiological practice. Hemangioma of the
      rib is rarely seen. CASE REPORT: We reported on a case of a rib lesion which had
      a classic imaging pattern of hemangioma. We highlighted the use of pre-operative
      embolization of such a vascular rib lesion before surgically removing the lesion
      by thoracotomy to reduce the risk of bleeding. CONCLUSIONS: We also emphasized
      overt complications of overzealous needling of such a vascular lesion for
      histopathological diagnosis as in our case.

PMID- 25866592
TI  - Epidemiology and management of antiretroviral-associated cardiovascular disease.
AB  - Risk and manifestations of cardiovascular disease (CVD) in patients infected with
      human immunodeficiency virus (HIV) will continue to evolve as improved treatments
      and life expectancy of these patients increases. Although initiation of
      antiretroviral (ARV) therapy has been shown to reduce this risk, some ARV
      medications may induce metabolic abnormalities, further compounding the risk of
      CVD. In this patient population, both pharmacologic and nonpharmacologic
      strategies should be employed to treat and reduce further risk of CVD. This
      review summarizes epidemiology data of the risk factors and development of CVD in
      HIV and provides recommendations to manage CVD in HIV-infected patients. 

PMID- 25866596
TI  - Recent Updates on the Efficacy of Group Based Treatments for Pediatric Obesity.
AB  - BACKGROUND: There is limited research on optimal treatment formats for childhood
      obesity. Group-based interventions are popular, but it is unclear whether
      outcomes can be obtained without an additional individual component. AIM: To
      examine statistically and clinically significant outcomes of recent group-based
      and mixed-format (group + Individual) pediatric obesity interventions. METHODS:
      Effect sizes and magnitudes of weight change were calculated for studies
      published between January 2013 and September 2014. RESULTS: Approximately half of
      the group-based studies reviewed produced significant results compared to
      control, and effect sizes were small. Mixed-format studies were less likely to
      include a control group, but those that did evidenced medium to large effects.
      Magnitudes of weight change post-intervention were generally greater in mixed
      format studies than group-only studies. CONCLUSIONS: Recent studies in pediatric
      obesity interventions suggest including an individual component in a group-based
      intervention produces optimal outcomes. Future research should directly compare
      group-only and mixed formats to confirm this observation.

PMID- 25866597
TI  - Sensitivity and Specificity of Self-Reported Olfactory Function in a Home-Based
      Study of Independent-Living, Healthy Older Women.
AB  - INTRODUCTION: The 2011-14 US National Health and Nutrition Examination Survey
      chemosensory protocol asks adults to self-rate their orthonasal (via nostrils)
      and retronasal (via mouth) smell abilities for subsequent odor identification
      testing. From data collected with a similar protocol, we aimed to identify a self
      reported olfactory index that showed the best sensitivity (correctly identifying
      dysfunction) and specificity (correctly indentifying normosmia) with measured
      olfaction. METHODS: In home-based testing, 121 independent-living older women
      (age 73+/-7 years) reported their olfactory function by interviewer-administered
      survey. Olfactory function was measured orthonasally via composite (odor
      threshold, identification task) or identification task alone. RESULTS: Only 16 %
      of women self-rated "below average" smell function. More women perceived loss of
      smell (38 %) or flavor (30 %) with aging. The rate of measured dysfunction was 30
      % by composite (threshold and identification) and 21.5 % by identification task,
      the latter misclassifying some mild dysfunction as normosmia. An index of self
      rated smell function and perceived loss yielded the most favorable sensitivity
      (65 %) and specificity (77 %) to measured function. Self-rated olfaction showed
      better agreement with severe measured dysfunction; mild dysfunction was less
      noticed. CONCLUSIONS: Self-reported indices that query about current and
      perceived changes in smell and flavor with aging showed better sensitivity
      estimates than those previously reported. Specificity was somewhat lower-some
      older adults may correctly perceive loss unidentified in a single assessment, or
      have a retronasal impairment that was undetected by an orthonasal measure.
      IMPLICATIONS: Our findings should inform self-rated measures that screen for
      severe olfactory dysfunction in clinical/community settings where testing is not
      routine.

PMID- 25866598
TI  - Intermittent and episode-driven use of pranlukast to reduce the frequency of
      wheezing in atopic children: a randomized, double-blind, placebo-controlled
      trial.
AB  - BACKGROUND: Leukotriene receptor antagonist (LTRA) therapy reduces asthma
      exacerbations in children older than 2 years. However, whether early intervention
      using LTRA in atopic smaller children aged 1 to 2 years who had experienced
      episodic wheezing can reduce the frequency of wheezing is unknown. METHODS: A
      randomized, double-blind, placebo-controlled, multi-center trial of episode
      driven intermittent use of pranlukast for 12 months, one of the LTRAs, was
      conducted by enrolling children who had two, but not more than two, episodes of
      wheezing prior to entry and were allergen-specific IgE-positive (>=class 2). The
      primary outcome was increased episodes of wheezing more than once a month for 3
      months. RESULTS: Seventy-seven children were randomly assigned to receive
      pranlukast (n = 37) or placebo (n = 40). The primary outcome occurred in 10 of 36
      (28%) of the pranlukast group and 14 of 39 (36%) in the placebo group, which was
      not significantly different (P = 0.45). Even though the study period was extended
      to a maximum of >5 years, there was no significant difference in the Kaplan-Meier
      curves in the occurrence of the primary outcome between the two groups.
      CONCLUSIONS: These results suggest that intermittent and episode-driven use of
      pranlukast in small children with a prior history of wheezing and atopic
      sensitization may not reduce the frequency of wheezing later in life. However,
      the sample size was too small to make a definitive conclusion. TRIAL
      REGISTRATION: UMIN000000634.

PMID- 25866599
TI  - The role of oxidative stress and autophagy in atherosclerosis.
AB  - Atherosclerosis is a multifactorial, multistep disorder of large- and medium
      sized arteries involving, in addition to age, gender and menopausal status, a
      complex interplay between lifestyle and genetic risk factors. Atherosclerosis
      usually begins with the diffusion and retention of atherogenic lipoproteins into
      the subendothelial space of the artery wall where they become oxidized by local
      enzymes and accumulate, leading to the formation of a cushion called atheroma or
      atheromatous or fibrofatty plaque, composed of a mixture of macrophages,
      lymphocytes, smooth muscle cells (SMCs), cholesterol cleft, necrotic debris, and
      lipid-laden foam cells. The pathogenesis of atherosclerosis still remains
      incompletely understood but emerging evidence suggests that it may involve
      multiple cellular events, including endothelial cell (EC) dysfunction,
      inflammation, proliferation of vascular SMCs, matrix (ECM) alteration, and
      neovascularization. Actually, a growing body of evidence indicates that autophagy
      along with the chronic and acute overproduction of reactive oxygen species (ROS)
      is integral to the development and progression of the disease and may represent
      fruitful avenues for biological investigation and for the identification of new
      therapeutic targets. In this review, we give an overview of ROS and autophagy in
      atherosclerosis as background to understand their potential role in this vascular
      disease. 

PMID- 25866600
TI  - Changes in the conformational state of hemoglobin in hemodialysed patients with
      chronic renal failure.
AB  - The aim of this study was to evaluate the properties of internal components of
      erythrocytes in chronic renal failure (CRF) patients undergoing hemodialysis (HD)
      in comparison to control subjects. For investigation of conformational state of
      hemoglobin and nonheme proteins (NHP) the maleimide spin label (MSL) in electron
      paramagnetic resonance (EPR) was applied. The studies were performed using MSL in
      whole cells and hemolysate as well as proteins separated by ion exchange
      chromatography and checked by electrophoresis. Additionally the level of -SH
      groups in hemolysate and isolated internal proteins of CRF erythrocytes was
      determined using 4,4'-dithiodipyridine. All measurements were performed before
      and after hemodialysis. Oxidative stress accompanying CRF/hemodialysed patients
      caused a significant decrease in the mobility of internal components inside
      erythrocytes indicated by MSL (P < 0.02). The significant decrease in mobility of
      spin labeled HbA1c and HbA both before and after HD (P < 0.0002) as well as in
      nonheme proteins before hemodialysis (P < 0.05) versus control was indicated.
      Decrease in mobility of internal components of erythrocytes was accompanied by
      loss of thiols before and after hemodialysis versus control in NHP (P < 0.05),
      HbA1c (P < 0.0002), and HbA (P < 0.0005). These findings showed oxidative
      influence of hemodialysis on hemoglobins and internal nonheme proteins in
      erythrocytes of CRF patients. 

PMID- 25866601
TI  - Non-invasive methods for the diagnosis of nonalcoholic fatty liver disease.
AB  - Nonalcoholic fatty liver disease (NAFLD) is the commonest chronic liver disease
      and includes simple steatosis and nonalcoholic steatohepatitis (NASH). Since NASH
      progresses to cirrhosis more frequently and increases liver-related and
      cardiovascular disease risk substantially more than simple steatosis, there is a
      great need to differentiate the two entities. Liver biopsy is the gold standard
      for the diagnosis of NAFLD but its disadvantages, including the risk of
      complications and sampling bias, stress the need for developing alternative
      diagnostic methods. Accordingly, several non-invasive markers have been evaluated
      for the diagnosis of simple steatosis and NASH, including both serological
      indices and imaging methods. The present review summarizes the current knowledge
      on the role of these markers in the diagnosis of NAFLD. Current data suggest that
      ultrasound and the fibrosis-4 score are probably the most appealing methods for
      detecting steatosis and for distinguishing NASH from simple steatosis,
      respectively, because of their low cost and relatively high accuracy. However,
      currently available methods, both serologic and imaging, cannot obviate the need
      for liver biopsy for diagnosing NASH due to their substantial false positive and
      false negative rates. Therefore, the current role of these methods is probably
      limited in patients who are unwilling or have contraindications for undergoing
      biopsy. 

PMID- 25866602
TI  - Strategies to improve outcome of patients with hepatocellular carcinoma receiving
      a liver transplantation.
AB  - Liver transplantation is the only therapeutic option which allows to treat both,
      the hepatocellular carcinoma and the underlying liver disease. Indeed, liver
      transplantation is considered the standard of care for a subset of patients with
      cirrhosis and hepatocellular carcinoma. However, tumour recurrence rates are as
      high as 20%, and once the recurrence is established the therapeutic options are
      scarce and with little impact on prognosis. Strategies to minimize tumour
      recurrence and thus to improve outcome may be classified into 3 groups: (1) An
      adequate selection of candidates for liver transplantation by using the Milan
      criteria; (2) An optimized management within waiting list including
      prioritization of patients at high risk of tumour progression, and the
      implementation of bridging therapies, particularly when the expected length
      within the waiting list is longer than 6 mo; and (3) Tailored immunosuppression
      comprising reduced exposure to calcineurin inhibitors, particularly early after
      liver transplantation, and the addition of mammalian target of rapamycin
      inhibitors. In the present manuscript the available scientific evidence
      supporting these strategies is comprehensively reviewed, and future directions
      are provided for novel research approaches, which may contribute to the final
      target: to cure more patients with hepatocellular carcinoma and with an improved
      long term outcome. 

PMID- 25866603
TI  - Arrhythmia risk in liver cirrhosis.
AB  - Interactions between the functioning of the heart and the liver have been
      described, with heart diseases affecting the liver, liver diseases affecting the
      heart, and conditions that simultaneously affect both. The heart is one of the
      most adversely affected organs in patients with liver cirrhosis. For example,
      arrhythmias and electrocardiographic changes are observed in patients with liver
      cirrhosis. The risk for arrhythmia is influenced by factors such as cirrhotic
      cardiomyopathy, cardiac ion channel remodeling, electrolyte imbalances, impaired
      autonomic function, hepatorenal syndrome, metabolic abnormalities, advanced age,
      inflammatory syndrome, stressful events, impaired drug metabolism and
      comorbidities. Close monitoring of cirrhotic patients is needed for arrhythmias,
      particularly when QT interval-prolonging drugs are given, or if electrolyte
      imbalances or hepatorenal syndrome appear. Arrhythmia risk may persist after
      liver transplantation due to possible QT interval prolongation, persistence of
      the parasympathetic impairment, post-transplant reperfusion and chronic
      immunosuppression, as well as consideration of the fact that the transplant
      itself is a stressful event for the cardiovascular system. The aims of the
      present article were to provide a review of the most important data regarding the
      epidemiology, pathophysiology, and biomarkers of arrhythmia risk in patients with
      liver cirrhosis, to elucidate the association with long-term outcome, and to
      propose future research directions. 

PMID- 25866605
TI  - Cirrhosis and portal hypertension: The importance of risk stratification, the
      role of hepatic venous pressure gradient measurement.
AB  - Portal hypertension is the main prognostic factor in cirrhosis. The recent
      emergence of potent antiviral drugs and new algorithm of treatment for the
      management of complications due to portal hypertension have sensibly changed our
      perception of cirrhosis that can be now considered as a multistage liver disease
      whose mortality risk can be reduced by a tailored approach for any stage of risk.
      Experts recommend to move toward a pathophysiological classification of cirrhosis
      that considers both structural and functional changes. The hepatic venous
      pressure gradient HVPG, is the reference gold standard to estimate the severity
      of portal hypertension in cirrhosis. It correlates with both structural and
      functional changes that occur in cirrhosis and carries valuable prognostic
      information to stratify the mortality risk. This article provides a general
      overview of the pathophysiology and natural course of cirrhosis and portal
      hypertension. We propose a simplified classification of cirrhosis based on low,
      intermediate and high mortality stage. The prognostic information provided by
      HVPG is presented according to each stage. A comparison with prognostic models
      based on clinical and endoscopic variables is discussed in order to evidence the
      additional contribute given by HVPG on top of other clinical and instrumental
      variables widely used in clinical practice. 

PMID- 25866604
TI  - Recent advances in multidisciplinary management of hepatocellular carcinoma.
AB  - The incidence of hepatocellular carcinoma (HCC) is increasing, and it is
      currently the second leading cause of cancer-related death worldwide. Potentially
      curative treatment options for HCC include resection, transplantation, and
      percutaneous ablation, whereas palliative treatments include trans-arterial
      chemoembolization (TACE), radioembolization, and systemic treatments. Due to the
      diversity of available treatment options and patients' presentations, a
      multidisciplinary team should decide clinical management of HCC, according to
      tumor characteristics and stage of liver disease. Potentially curative treatments
      are suitable for very-early- and early-stage HCC. However, the vast majority of
      HCC patients are diagnosed in later stages, where the tumor characteristics or
      progress of liver disease prevent curative interventions. For patients with
      intermediate-stage HCC, TACE and radioembolization improve survival and are being
      evaluated in addition to potentially curative therapies or with systemic targeted
      therapy. There is currently no effective systemic chemotherapy, immunologic, or
      hormonal therapy for HCC, and sorafenib is the only approved molecular-targeted
      treatment for advanced HCC. Other targeted agents are under investigation; trials
      comparing new agents in combination with sorafenib are ongoing. Combinations of
      systemic targeted therapies with local treatments are being evaluated for further
      improvements in HCC patient outcomes. This article provides an updated and
      comprehensive overview of the current standards and trends in the treatment of
      HCC. 

PMID- 25866606
TI  - Host cellular microRNA involvement in the control of hepatitis B virus gene
      expression and replication.
AB  - A large number of studies have demonstrated that the synergistic collaboration of
      a number of microRNAs (miRNAs), their growth factors and their downstream agents
      is required for the initiation and completion of pathogenesis in the liver.
      miRNAs are thought to exert a profound effect on almost every aspect of liver
      biology and pathology. Accumulating evidence indicates that several miRNAs are
      involved in the hepatitis B virus (HBV) life cycle and infectivity, in addition
      to HBV-associated liver diseases including fibrosis, cirrhosis and hepatocellular
      carcinoma (HCC). In turn, HBV can modulate the expression of several cellular
      miRNAs, thus promoting a favorable environment for its replication and survival.
      In this review, we focused on the involvement of host cellular miRNAs that are
      directly and indirectly associated with HBV RNA or HBV associated transcription
      factors. Exploring different facets of the interactions among miRNA, HBV and HCV
      infections, and the carcinogenesis and progress of HCC, could facilitate the
      development of novel and effective treatment approaches for liver disease. 

PMID- 25866607
TI  - Pre-treatment prediction of response to peginterferon plus ribavirin in chronic
      hepatitis C genotype 3.
AB  - AIM: To evaluate pre-treatment factors associated with sustained virological
      response (SVR) in patients with hepatitis C virus (HCV) genotype 3 treated with
      peginterferon and ribavirin (RBV). METHODS: We retrospectively analyzed treatment
      naive, mono-infected HCV genotype 3 patients treated with peginterferon and RBV.
      Exclusion criteria included presence of other liver disease, alcohol consumption
      and African American or Asian ethnicity. The variables collected and compared
      between patients who achieved an SVR and patients who did not were as follows:
      gender, age, fibrosis stage, diabetes, body mass index, steatosis, INFL3
      polymorphism, pre-treatment HCV-RNA, type of peginterferon, RBV dose and
      adherence. RESULTS: A total of 107 patients treated between June, 2004 and March,
      2013 were included. Mean treatment duration was 25.1 (+/- 1.8) wk. Overall, 58%
      (62/107) of the patients achieved an SVR and 42% (45/107) did not. In the
      multivariate logistic regression analysis, pre-treatment HCV-RNA >= 600000 UI/mL
      (OR = 0.375, 95%CI: 0.153-0.919, P = 0.032) and advanced fibrosis (OR = 0.278,
      95%CI: 0.113-0.684, P = 0.005) were significantly associated with low SVR rates.
      In patients with pre-treatment HCV-RNA >= 600000 UI/mL and advanced fibrosis, the
      probability of achieving an SVR was 29% (95%CI: 13.1-45.2). In patients with pre
      treatment HCV-RNA < 600000 UI/mL and mild to moderate fibrosis, the probability
      of achieving an SVR was 81% (95%CI: 68.8-93.4). CONCLUSION: In patients with HCV
      genotype 3 infections the presence of advance fibrosis and high pre-treatment
      viral load might be associated with poor response to peginterferon plus RBV.
      These patients could benefit the most from new direct antiviral agents-based
      regimes.

PMID- 25866608
TI  - Endotipsitis: A case report with a literature review on an emerging prosthetic
      related infection.
AB  - AIM: To investigate the etiology and management of a poorly understood
      complication of transjugular intrahepatic portosystemic shunt; "endotipsitis".
      METHODS: A MEDLINE database search was carried out, reviewing all papers with
      specific words in the title or abstract, and excluding appropriately. Of 283
      papers that were reviewed, 22 papers reporting 53 cases in total were included in
      the analyses. RESULTS: No predominant etiology for endotipsitis was identified,
      but gram-positive organisms were more common among early-onset infections (P <
      0.01). A higher mortality rate was associated with Staphylococcus aureus and
      Candida spp infections (P < 0.01). There was no trend in choice of antibiotic
      based on the microorganisms isolated and treatment varied from the guidelines of
      other vegetative prosthetic infections. In endotipsitis "high risk" organisms
      have been identified, emphasizing the importance of ensuring optimal
      antimicrobial therapy and adjunctive management strategies. CONCLUSION: Higher
      mortality rate was associated with Staphylococcus aureus and Candida spp
      infections. A prospective multicenter trial is needed before specific treatment
      can be recommended.

PMID- 25866609
TI  - Skin cancer in immunosuppressed transplant patients: Vigilance matters.
AB  - Liver transplantation (LT) is a widely-accepted, definitive therapy of
      irreversible liver diseases including hepatitis C, alcoholic liver disease and
      metabolic liver disease. After transplantation, patients generally use a variety
      of immunosuppressive medications for the rest of their lives to prevent rejection
      of transplanted liver. Mortality after LT is mainly caused by recurrence of
      alcoholic hepatitis which is mostly seen in the patients who resume heavy
      drinking. On the other hand, de-novo malignancies after LT are not seldom. Skin
      cancers make up 13.5% of the de-novo malignancies seen in these patients.
      Malignancies tend to affect survival earlier in the course with a 53% risk of
      death at 5 years after diagnosis. We aimed to report a case who underwent LT
      secondary to alcoholic liver disease and developed squamous cell carcinoma of the
      skin eighteen years after transplantation. In summary, transplant recipients are
      recommended to be educated on self examination for skin cancer; health care
      providers should be further suspicious during routine dermatological examinations
      of the transplant patients and biopsies of possible lesions for skin cancer is
      warranted even many years after transplantation. 

PMID- 25866610
TI  - First jejunal artery, an alternative graft for right hepatic artery
      reconstruction.
AB  - Common bile duct cancer invading right hepatic artery is sometimes diagnosed
      intraoperatively. Excision and safe reconstruction of the artery with suitable
      graft is essential. Arterial reconstruction with autologous saphenous vein graft
      is the preferred method practiced routinely. However the right hepatic artery
      reconstruction has also been carried out with several other vessels like
      gastroduodenal artery, right gastroepiploic artery or the splenic artery. We
      report a case of 63-year-old man presenting with history of progressive jaundice,
      pruritus and impaired appetite. Following various imaging modalities including
      computed tomography, endoscopic retrograde cholangiopancreatography, magnetic
      resonance cholangiopancreatography, intraductal ultrasound extrahepatic bile duct
      cancer was diagnosed; however, none of those detected vessel invasion.
      Intraoperatively, right hepatic artery invasion was revealed. Right hepatic
      artery was resected and reconstructed with a graft harvested from the first
      jejunal artery (JA). Postoperative outcome was satisfactory with a long-term
      graft patency. First JA can be a reliable graft option for right hepatic artery
      reconstruction. 

PMID- 25866611
TI  - New Insights into Protein (Un)Folding Dynamics.
AB  - A fundamental open problem in biophysics is how the folded structure of the main
      chain (MC) of a protein is determined by the physics of the interactions between
      the side chains (SCs). All-atom molecular dynamics simulations of a model protein
      (Trp-cage) revealed that strong correlations between the motions of the SCs and
      the MC occur transiently at 380 K in unfolded segments of the protein and during
      the simulations of the whole amino-acid sequence at 450 K. The high correlation
      between the SC and MC fluctuations is a fundamental property of the unfolded
      state and is also relevant to unstructured proteins as intrinsically disordered
      proteins (IDPs), for which new reaction coordinates are introduced. The presented
      findings may open a new door as to how functions of IDPs are related to
      conformations, which play a crucial role in neurodegenerative diseases.

PMID- 25866612
TI  - Using description logics to evaluate the consistency of drug-class membership
      relations in NDF-RT.
AB  - BACKGROUND: The NDF-RT (National Drug File Reference Terminology) is an ontology,
      which describes drugs and their properties and supports computerized physician
      order entry systems. NDF-RT's classes are mostly specified using only necessary
      conditions and lack sufficient conditions, making its use limited until recently,
      when asserted drug-class relations were added. The addition of these asserted
      drug-class relations presents an opportunity to compare them with drug-class
      relations that can be inferred using the properties of drugs and drug classes in
      NDF-RT. METHODS: We enriched NDF-RT's drug-classes with sufficient conditions,
      added property equivalences, and then used an OWL reasoner to infer drug-class
      membership relations. We compared the inferred class relations to the recently
      added asserted relations derived from FDA Structured Product Labels. RESULTS: The
      inferred and asserted relations only match in about 50% of the cases, due to
      incompleteness of the drug descriptions and quality issues in the class
      definitions. CONCLUSIONS: This investigation quantifies and categorizes the
      disparities between asserted and inferred drug-class relations and illustrates
      issues with class definitions and drug descriptions. In addition, it serves as an
      example of the benefits DL can add to ontology development and evaluation.

PMID- 25866613
TI  - mizer: an R package for multispecies, trait-based and community size spectrum
      ecological modelling.
AB  - Size spectrum ecological models are representations of a community of individuals
      which grow and change trophic level. A key emergent feature of these models is
      the size spectrum; the total abundance of all individuals that scales negatively
      with size. The models we focus on are designed to capture fish community dynamics
      useful for assessing the community impacts of fishing.We present mizer, an R
      package for implementing dynamic size spectrum ecological models of an entire
      aquatic community subject to fishing. Multiple fishing gears can be defined and
      fishing mortality can change through time making it possible to simulate a range
      of exploitation strategies and management options.mizer implements three versions
      of the size spectrum modelling framework: the community model, where individuals
      are only characterized by their size; the trait-based model, where individuals
      are further characterized by their asymptotic size; and the multispecies model
      where additional trait differences are resolved.A range of plot, community
      indicator and summary methods are available to inspect the results of the
      simulations.

PMID- 25866614
TI  - Personal messages reduce vandalism and theft of unattended scientific equipment.
AB  - Scientific equipment, such as animal traps and autonomous data collection
      systems, is regularly left in the field unattended, making it an easy target for
      vandalism or theft. We tested the effectiveness of three label types, which
      differed in their information content and tone of the message, that is,
      personal,neutral or threatening, for reducing incidents of vandalism and theft of
      unattended scientific field equipment. The three label types were attached to 20
      scientific equipment dummies each, which were placed semi-hidden and evenly
      distributed in four public parks in Munich, Germany. While the label type had no
      effect on the severity of the interactions with our equipment dummies, the
      personal label reduced the overall number of interactions by c. 40-60%, compared
      with the dummies showing the neutral or threatening label type. We suggest that
      researchers, in addition to securing their field equipment, label it with
      personal and polite messages that inform about the ongoing research and directly
      appeal to the public not to disturb the equipment. Further studies should extend
      these results to areas with different socio-economic structure.

PMID- 25866615
TI  - Evaluation and management implications of uncertainty in a multispecies size
      structured model of population and community responses to fishing.
AB  - Implementation of an ecosystem approach to fisheries requires advice on trade
      offs among fished species and between fisheries yields and biodiversity or food
      web properties. However, the lack of explicit representation, analysis and
      consideration of uncertainty in most multispecies models has limited their
      application in analyses that could support management advice.We assessed the
      consequences of parameter uncertainty by developing 78 125 multispecies size
      structured fish community models, with all combinations of parameters drawn from
      ranges that spanned parameter values estimated from data and literature. This
      unfiltered ensemble was reduced to 188 plausible models, the filtered ensemble
      (FE), by screening outputs against fish abundance data and ecological principles
      such as requiring species' persistence.Effects of parameter uncertainty on
      estimates of single-species management reference points for fishing mortality
      (FMSY, fishing mortality rate providing MSY, the maximum sustainable yield) and
      biomass (BMSY, biomass at MSY) were evaluated by calculating probability
      distributions of estimated reference points with the FE. There was a 50%
      probability that multispecies FMSY could be estimated to within +/-25% of its
      actual value, and a 50% probability that BMSY could be estimated to within +/-40%
      of its actual value.Signal-to-noise ratio was assessed for four community
      indicators when mortality rates were reduced from current rates to FMSY. The
      slope of the community size spectrum showed the greatest signal-to-noise ratio,
      indicating that it would be the most responsive indicator to the change in
      fishing mortality F. Further, the power of an ongoing international monitoring
      survey to detect predicted responses of size spectrum slope was higher than for
      other size-based metrics.Synthesis and applications: Application of the ensemble
      model approach allows explicit representation of parameter uncertainty and
      supports advice and management by (i) providing uncertainty intervals for
      management reference points, (ii) estimating working values of reference points
      that achieve a defined reduction in risk of not breaching the true reference
      point, (iii) estimating the responsiveness of population, community, food web and
      biodiversity indicators to changes in F, (iv) assessing the performance of
      indicators and monitoring programmes and (v) identifying priorities for data
      collection and changes to model structure to reduce uncertainty.

PMID- 25866616
TI  - Y genetic variation and phenotypic diversity in health and disease.
AB  - Sexually dimorphic traits arise through the combined effects of sex hormones and
      sex chromosomes on sex-biased gene expression, and experimental mouse models have
      been instrumental in determining their relative contribution in modulating sex
      differences. A role for the Y chromosome (ChrY) in mediating sex differences
      outside of development and reproduction has historically been overlooked due to
      its unusual genetic composition and the predominant testes-specific expression of
      ChrY-encoded genes. However, ample evidence now exists supporting ChrY as a
      mediator of other physiological traits in males, and genetic variation in ChrY
      has been linked to several diseases, including heart disease, cancer, and
      autoimmune diseases in experimental animal models, as well as humans. The genetic
      and molecular mechanisms by which ChrY modulates phenotypic variation in males
      remain unknown but may be a function of copy number variation between homologous
      X-Y multicopy genes driving differential gene expression. Here, we review the
      literature identifying an association between ChrY polymorphism and phenotypic
      variation and present the current evidence depicting the mammalian ChrY as a
      member of the regulatory genome in males and as a factor influencing paternal
      parent-of-origin effects in female offspring. 

PMID- 25866617
TI  - Estrogens increase expression of bone morphogenetic protein 8b in brown adipose
      tissue of mice.
AB  - BACKGROUND: In mammals, white adipose tissue (WAT) stores fat and brown adipose
      tissue (BAT) dissipates fat to produce heat. Several studies showed that females
      have more active BAT. Members of the bone morphogenetic protein (BMP) and
      fibroblast growth factor (FGF) families are expressed in BAT and are involved in
      BAT activity. We hypothesized that differential expression of BMPs and FGFs might
      contribute to sex differences in BAT activity. METHODS: We investigated the
      expression of BMPs and FGFs in BAT of male and female C57BL/6J mice upon
      gonadectomy, cold exposure, and exposure to sex steroids. RESULTS: Of the FGF
      family, BAT Fgf1, Fgf9, Fgf18, and Fgf21 expression was induced upon cold
      exposure, but only Fgf1 expression was obviously different between the sexes:
      females had 2.5-fold lower BAT Fgf1 than males. Cold exposure induced BAT Bmp4
      and Bmp8b expression, but only Bmp8b differed between the sexes: females had 35
      fold higher BAT Bmp8b than males. Ovariectomy almost completely blunted BAT Bmp8b
      expression, while orchidectomy had no effect. Male mice and ovariectomized female
      mice treated with diethylstilbestrol (DES) had approximately 350-fold and
      approximately 36-fold higher BAT Bmp8b expression, respectively. Ninety-day and 7
      day treatment of female mice with dihydrotestosterone (DHT) decreased BAT Bmp8b
      expression by approximately fivefold and approximately fourfold, respectively.
      Finally, treatment of primary murine brown adipocytes with DES did not result in
      changes in Bmp8b expression. CONCLUSIONS: BAT Bmp8b expression in mice is
      positively regulated by presence of ovaries and estrogens such as DES.

PMID- 25866618
TI  - A literature review of clinical tests for lumbar instability in low back pain:
      validity and applicability in clinical practice.
AB  - BACKGROUND: Several clinical tests have been proposed on low back pain (LBP), but
      their usefulness in detecting lumbar instability is not yet clear. The objective
      of this literature review was to investigate the clinical validity of the main
      clinical tests used for the diagnosis of lumbar instability in individuals with
      LBP and to verify their applicability in everyday clinical practice. METHODS: We
      searched studies of the accuracy and/or reliability of Prone Instability Test
      (PIT), Passive Lumbar Extension Test (PLE), Aberrant Movements Pattern (AMP),
      Posterior Shear Test (PST), Active Straight Leg Raise Test (ASLR) and Prone and
      Supine Bridge Tests (PB and SB) in Medline, Embase, Cinahl, PubMed, and Scopus
      databases. Only the studies in which each test was investigated by at least one
      study concerning both the accuracy and the reliability were considered eligible.
      The quality of the studies was evaluated by QUADAS and QAREL scales. RESULTS: Six
      papers considering 333 LBP patients were included. The PLE was the most accurate
      and informative clinical test, with high sensitivity (0.84, 95% CI: 0.69 - 0.91)
      and high specificity (0.90, 95% CI: 0.85 -0.97). The diagnostic accuracy of AMP
      depends on each singular test. The PIT and the PST demonstrated by fair to
      moderate sensitivity and specificity [PIT sensitivity = 0.71 (95% CI: 0.51 -
      0.83), PIT specificity = 0.57 (95% CI: 039 - 0.78); PST sensitivity = 0.50 (95%
      CI: 0.41 - 0.76), PST specificity = 0.48 (95% CI: 0.22 - 0.58)]. The PLE showed a
      good reliability (k = 0.76), but this result comes from a single study. The inter
      rater reliability of the PIT ranged by slight (k = 0.10 and 0.04), to good (k =
      0.87). The inter-rater reliability of the AMP ranged by slight (k = -0.07) to
      moderate (k = 0.64), whereas the inter-rater reliability of the PST was fair (k =
      0.27). CONCLUSIONS: The data from the studies provided information on the methods
      used and suggest that PLE is the most appropriate tests to detect lumbar
      instability in specific LBP. However, due to the lack of available papers on
      other lumbar conditions, these findings should be confirmed with studies on non
      specific LBP patients.

PMID- 25866620
TI  - A critical evaluation of science outreach via social media: its role and impact
      on scientists.
AB  - The role of scientists in social media and its impact on their careers are not
      fully explored.  While policies and best practices are still fluid, it is
      concerning that discourse is often based on little to no data, and some arguments
      directly contradict the available data.  Here, we consider the relevant but
      subjective questions about social media for science outreach (SOSM),
      specifically: (1) Does a public relations nightmare exist for science?; (2) Why
      (or why aren't) scientists engaging in social media?; (3) Are scientists using
      social media well?; and (4) Will social media benefit a scientist's career? We
      call for the scientific community to create tangible plans that value, measure,
      and help manage scientists' social media engagement. 

PMID- 25866619
TI  - Differential cytokine expression by brain microglia/macrophages in primary
      culture after oxygen glucose deprivation and their protective effects on
      astrocytes during anoxia.
AB  - BACKGROUND: Activation of microglia/macrophages following cerebral ischemia may
      be beneficial or detrimental for the survival of brain cells, an ambiguity in
      effects that has been explained by findings that ischemia can induce
      transformation of resting monocytes/macrophages into two different inflammation
      related phenotypes, termed M1 and M2. The extent to which this differentiation
      depends on paracrine signaling from other brain cells is not clear. This study
      explored if oxygen glucose deprivation (OGD) can trigger expression of phenotype
      specific markers in rat microglia/macrophages in primary culture, in absence/low
      abundance of other brain cells. Time pattern of these changes was assessed and
      compared to time-pattern that has been revealed in vivo previously. Effects of
      phenotype-specific cytokines on viability of astrocytes in primary culture during
      anoxia were also explored. METHODS: Primary cultures of rat microglia/macrophages
      were exposed to 2h OGD and then incubated further under normal conditions; this
      was considered as a recovery period. Expression of mRNA for specific markers and
      secretion of phenotype-specific cytokines were explored at different time points
      by real time PCR and ELISA, respectively. Effects of cytokines that were secreted
      by microglia in primary culture after OGD on viability of astrocytes were
      determined. RESULTS: Expression and secretion of M2 phenotype-specific markers
      and/or cytokines after OGD increased early after OGD and then decreased in the
      later stages of the recovery period. Expression and secretion of M1 phenotype
      specific markers and cytokines did not show a common time pattern, but there was
      a tendency for an increase during the recovery period. All M1 phenotype-specific
      and two out of the three tested M2 phenotype-specific cytokines revealed
      protective effects on astrocytes during near-anoxia by a marked reduction of
      apoptosis. CONCLUSIONS: Time-pattern of expression/secretion of phenotype
      specific markers suggested that polarization of the brain microglia/macrophages
      in vitro to M2 and M1 phenotypes were largely independent and likely dependent on
      signaling from other brain cells, respectively. Time-pattern of polarization to
      the M2 phenotype partially resembled time-pattern that has been seen in vivo.
      Effects of M1 phenotype-specific cytokines on primary culture of astrocytes were
      protective, thus largely opposite to effects that have been observed in vivo.

PMID- 25866621
TI  - Further available immunization option to prevent pneumococcal disease.
AB  - In their recent review, Charles Feldman and Ronald Anderson provide an overview
      of various clinical aspects of pneumococcal infections. We would like to complete
      this report by providing some additional information on a widely-used
      immunization option, which was not originally mentioned in the article. The
      protein D pneumococcal conjugate vaccine (PHiD-CV) has been pre-approved by WHO
      and its impact is supported by real-life data from the regions of its use. 

PMID- 25866622
TI  - Effects of mutations on the molecular dynamics of oxygen escape from the dimeric
      hemoglobin of Scapharca inaequivalvis.
AB  - Like many hemoglobins, the structure of the dimeric hemoglobin from the clam
      Scapharca inaequivalvis is a "closed bottle" since there is no direct tunnel from
      the oxygen binding site on the heme to the solvent.  The proximal histidine faces
      the dimer interface, which consists of the E and F helicies.  This is
      significantly different from tetrameric vertebrate hemoglobins and brings the
      heme groups near the subunit interface. The subunit interface is also
      characterized by an immobile, hydrogen-bonded network of water molecules. 
      Although there is data which is consistent with the histidine gate pathway for
      ligand escape, these aspects of the structure would seem to make that pathway
      less likely. Locally enhanced sampling molecular dynamics are used here to
      suggest alternative pathways in the wild-type and six mutant proteins. In most
      cases the point mutations change the selection of exit routes observed in the
      simulations. Exit via the histidine gate is rarely seem although oxygen molecules
      do occasionally cross over the interface from one subunit to the other. The
      results suggest that changes in flexibility and, in some cases, creation of new
      cavities can explain the effects of the mutations on ligand exit paths. 

PMID- 25866623
TI  - The culture of scientific research.
AB  - In 2014, the UK-based Nuffield Council on Bioethics carried out a series of
      engagement activities, including an online survey to which 970 people responded,
      and 15 discussion events at universities around the UK to explore the culture of
      research in the UK and its effect on ethical conduct in science and the quality
      of research. The findings of the project were published in December 2014 and the
      main points are summarised here. We found that scientists are motivated in their
      work to find out more about the world and to benefit society, and that they
      believe collaboration, multidisciplinarity, openness and creativity are important
      for the production of high quality science. However, in some cases, our findings
      suggest, the culture of research in higher education institutions does not
      support or encourage these goals or activities. For example, high levels of
      competition and perceptions about how scientists are assessed for jobs and
      funding are reportedly contributing to a loss of creativity in science, less
      collaboration and poor research practices. The project led to suggestions for
      action for funding bodies, research institutions, publishers and editors,
      professional bodies and individual researchers. 

PMID- 25866624
TI  - Selective cell elimination in vitro and in vivo from tissues and tumors using
      antibodies conjugated with a near infrared phthalocyanine.
AB  - Cell cultures and tissues often contain cellular subpopulations that potentially
      interfere with or contaminate other cells of interest. However, it is difficult
      to eliminate unwanted cells without damaging the very cell population one is
      seeking to protect, especially established tissue. Here, we report a method of
      eliminating a specific subpopulation of cells from a mixed 2D or 3D cell culture
      in vitro and a mixed-population in vivo tumor model by using antibody
      photosensitizer conjugates (APC) with a near infrared (NIR) phthalocyanine
      derivative (IRdye700DX, IR700) combined with NIR light exposure with minimal
      damage to non-targeted cells. Thus, APC combined with NIR light exposure holds
      promise as a method of removing specific cells from mixed cell cultures and
      tumors.

PMID- 25866625
TI  - Burden of frailty in the elderly population: perspectives for a public health
      challenge.
AB  - Frailty is a major health condition associated with ageing. Although the concept
      is almost universally accepted, its operational definition remains controversial.
      Anyway, this geriatric condition represents a huge potential public health issue
      at both the patient and the societal levels because of its multiple clinical,
      societal consequences and its dynamic nature. Here, we review existing
      definitions and assessment tools for frailty, we highlight consequences of this
      geriatric condition and we discuss the importance of its screening and prevention
      to limit its public health burden. 

PMID- 25866626
TI  - Ebola, the killer virus.
AB  - Ebola virus disease (EVD) has mostly affected economically deprived countries as
      limited resources adversely affect a country's infrastructure and administration.
      Probing into the factors that led to the widespread outbreak, setting forth plans
      to counter EVD cases in developing countries, and devising definitive measures to
      limit the spread of the disease are essential steps that must be immediately
      taken. In this review we summarize the pathogenesis of EVD and the factors that
      led to its spread. We also highlight interventions employed by certain countries
      that have successfully limited the epidemic, and add a few preventive measures
      after studying the current data. According to the available data, barriers to
      prevent and control the disease in affected countries include irresolute and
      disorganized health systems, substandard sanitary conditions, poor personal
      hygiene practices, and false beliefs and stigma related to EVD. The public health
      sector along with the respective chief authorities in developing countries must
      devise strategies, keeping the available resources in mind, to deal with the
      outbreak before it occurs. As a first step, communities should be educated on
      EVD's symptoms, history, mode of transmission, and methods of protection,
      including the importance of personal hygiene practices, via seminars, newspapers,
      and other social media. A popular opinion leader (POL) giving this information
      would further help to remove the misconception about the nature of the disease
      and indirectly improve the quality of life of affected patients and their
      families. 

PMID- 25866627
TI  - Bulimia Nervosa - medical complications.
AB  - As with anorexia nervosa, there are many medical complications associated with
      bulimia nervosa. In bulimia nervosa, these complications are a direct result of
      both the mode and the frequency of purging behaviours. For the purposes of this
      article, we will review in detail the many complications of the two major modes
      of purging, namely, self-induced vomiting and laxative abuse; these two account
      for more than 90% of purging behaviours in bulimia nervosa. Some of these
      complications are potentially extremely dangerous and need to be well understood
      to effectively treat patients with bulimia nervosa. Other methods of purging,
      such as diuretic abuse, are much less frequently utilized and will only be
      mentioned briefly. In a subsequent article, the treatments of these medical
      complications will be presented. 

PMID- 25866628
TI  - Novel CLC3 transcript variants in blood eosinophils and increased CLC3 expression
      in nasal lavage and blood eosinophils of asthmatics.
AB  - Eosinophilia is a characteristic feature of allergic airway inflammation and
      remodeling. Chloride channel-3 (CLC3) in eosinophils has been associated with
      superoxide generation and respiratory burst. The CLC3 gene may produce multiple
      transcript variants through alternative splicing. However, the presence of CLC3
      variants in human eosinophils is unknown. We examined the expression of CLC3
      transcript variants in peripheral blood eosinophils of allergic asthmatics and
      healthy individuals. Potential of these obligatory dimers to form homo- or hetero
      dimers was examined in HEK293 cells co-transfected with CLC3b-GFP and CLC3e-RFP.
      Eosinophils were isolated from peripheral blood by negative selection. Expression
      of CLC3 and CLC3 transcript variants was examined by qPCR, Western blot, and
      immunofluorescence. Confocal micrographs were analyzed with Image J software.
      Higher levels of novel transcript variants of CLC3 (CLC3b and CLC3e) were found
      in peripheral blood eosinophils of asthmatics compared to healthy non-atopic
      subjects. We also found higher CLC3 protein expression in the blood and nasal
      lavage eosinophils of asthmatics than healthy subjects. Both membranous and
      intracellular CLC3 expression were observed. Also, we found the presence of both
      homodimers and heterodimers of CLC3b-GFP and CLC3e-RFP in HEK293 cells. Higher
      and differential expression of novel CLC3 transcript variants in mild-to-moderate
      and moderate-to-severe asthmatic eosinophils suggest their critical role in
      allergic asthma. Membranous and intracellular (granular) expression of CLC3 in
      nasal lavage and peripheral blood eosinophils suggest their involvement in the
      activation and migration of eosinophils in allergic asthma. Moreover, homo- and
      hetero-dimerization of these transcript variants may change the channel
      properties to exhibit these states. Presence of CLC3 variants may serve as a
      biomarker in allergic asthma and additional knowledge of interaction between CLC3
      transcript variants and their specific role in the activation and migration of
      eosinophils will allow to explore novel therapeutic approach in allergic asthma. 

PMID- 25866629
TI  - Effects of lasofoxifene and bazedoxifene on B cell development and function.
AB  - The third generation selective estrogen receptor modulators lasofoxifene (las)
      and bazedoxifene (bza) are indicated for treatment of postmenopausal
      osteoporosis. 17beta-Estradiol (E2) and the second generation SERM raloxifene
      (ral) have major effects on the immune system, particularly on B cells. Treatment
      with E2 or ral inhibits B lymphopoiesis and treatment with E2, but not ral,
      stimulates antibody production. The effects of las and bza on the immune system
      have not been studied. Therefore, the aim of this study was to investigate their
      role in B cell development, maturation, and function. C57BL/6 mice were sham
      operated or ovariectomized (ovx) and treated with vehicle, E2, ral, las, or bza.
      All substances increased total bone mineral density in ovx mice, as measured by
      peripheral quantitative computed tomography. In uterus, bza alone lacked
      agonistic effect in ovx mice and even acted as an antagonist in sham mice. As
      expected, E2 decreased B cell numbers at all developmental stages from pre-BI
      cells (in bone marrow) to transitional 1 (T1) B cells (in spleen) and increased
      marginal zone (MZ) B cells as determined by flow cytometry. However, treatment
      with las or bza only decreased the last stages of bone marrow B cell development
      and splenic T1 B cells, but had no effect MZ B cells. E2 increased antibody
      producing cells quantified by ELISPOT, but las or bza did not. In conclusion, las
      and bza differ from E2 by retaining normal number of cells at most B cell stages
      during B lymphopoiesis and maturation and by not increasing antibody-producing
      cells. 

PMID- 25866630
TI  - Chaperoned amyloid proteins for immune manipulation: alpha-Synuclein/Hsp70 shifts
      immunity toward a modulatory phenotype.
AB  - alpha-Synuclein (alphaSyn) is a 140-residue amyloid-forming protein whose
      aggregation is linked to Parkinson's disease (PD). It has also been found to play
      a critical role in the immune imbalance that accompanies disease progression, a
      characteristic that has prompted the search for an effective alphaSyn-based
      immunotherapy. In this study, we have simultaneously exploited two important
      features of certain heat-shock proteins (HSPs): their classical "chaperone"
      activities and their recently discovered and diverse "immunoactive" properties.
      In particular, we have explored the immune response elicited by immunization of
      C57BL/6 mice with an alphaSyn/Hsp70 protein combination in the absence of added
      adjuvant. Our results show differential effects for mice immunized with the
      alphaSyn/Hsp70 complex, including a restrained alphaSyn-specific (IgM and IgG)
      humoral response as well as minimized alterations in the Treg
      (CD4(+)CD25(+)Foxp3(+)) and Teff (CD4(+)Foxp3(-)) cell populations, as opposed to
      significant changes in mice immunized with alphaSyn and Hsp70 alone. Furthermore,
      in vitro-stimulated splenocytes from immunized mice showed the lowest relative
      response against alphaSyn challenge for the "alphaSyn/Hsp70" experimental group
      as measured by IFN-gamma and IL-17 secretion, and higher IL-10 levels when
      stimulated with LPS. Finally, serum levels of Th1-cytokine IFN-gamma and
      immunomodulatory IL-10 indicated a unique shift toward an
      immunomodulatory/immunoprotective phenotype in mice immunized with the
      alphaSyn/Hsp70 complex. Overall, we propose the use of functional "HSP-chaperoned
      amyloid/aggregating proteins" generated with appropriate HSP-substrate protein
      combinations, such as the alphaSyn/Hsp70 complex, as a novel strategy for immune
      based intervention against synucleinopathies and other amyloid or "misfolding"
      neurodegenerative disorders. 

PMID- 25866631
TI  - CD24 activates the NLRP3 inflammasome through c-Src kinase activity in a model of
      the lining epithelium of inflamed periodontal tissues.
AB  - Chronic periodontitis is characterized by perturbation of the epithelial
      attachment to the tooth with subsequent migration of the lining epithelium and
      formation of a cleft or pocket. This non-keratinized lining epithelium provides
      initial responses to bacterial products by signalling through receptors of innate
      immunity to activate inflammasome pathways. These comprise an intracellular
      network of regulatory and effector molecules leading to synthesis and activation
      of pro-inflammatory cytokines. Conversely, CD24 is characteristically strongly
      expressed by the pocket epithelium and is reported to function as an important
      negative regulator for danger signals, protecting tissues from excessive
      leukocyte activity. The objective of the study was to determine the impact of
      ligation of CD24 on expression of inflammasome components. An epithelial mimic of
      pocket epithelium was used to evaluate activation of the NLRP3 inflammasome
      pathway. Surprisingly, antibody ligation of CD24 enhanced expression of NLRP3
      together with co-activators ASC and caspase-1 resulting in burst release of
      activated interleukin (IL)-18. Potent product inhibition was detected with IL-18
      suppressing expression of NLRP3, ASC, and caspase-1. Scant distribution of these
      products within pocket epithelium compared with healthy gingival attachment
      provided indication of potential cycling of NLRP3 inflammasome expression. As
      subjects with mild chronic periodontitis have increased titres of serum
      antibodies auto-reactive with CD24 compared with those of subjects with severe
      periodontitis, a molecular mechanism for regulated expression of the NLRP3
      inflammasome mediated by c-Src kinase activity, is proposed. This pathway could
      be regionally disrupted by products of pathogenic bacteria with profound
      downregulation in the dysbiosis associated with severe disease. 

PMID- 25866632
TI  - High fat diet deviates PtC-specific B1 B cell phagocytosis in obese mice.
AB  - Phagocytosis had been attributed predominantly to "professional" phagocytes such
      as macrophages, which play critical roles in adipose tissue inflammation.
      However, recently, macrophage-like phagocytic activity has been reported in B1 B
      lymphocytes. Intrigued by the long-established correlation between high fat diet
      (HFD)-induced obesity and immune dysfunction, we investigated how HFD affects B1
      B cell phagocytosis. A significant number of B1 B cells recognize
      phosphatidylcholine (PtC), a common phospholipid component of cell membrane. We
      report here that unlike macrophages, B1 B cells have a unique PtC-specific
      phagocytic function. In the presence of both PtC-coated and non-PtC control
      fluorescent nano-particles, B1 B cells from healthy lean mice selectively
      engulfed PtC-coated beads, whereas B1 B cells from HFD-fed obese mice non
      discriminately phagocytosed both PtC-coated and control beads. Morphologically,
      B1 B cells from obese mice resembled macrophages, displaying enlarged cytosol and
      engulfed more beads. Our study suggests for the first time that HFD can affect B1
      B cell phagocytosis, substantiating the link of HFD-induced obesity and immune
      deviation. 

PMID- 25866633
TI  - Midline 1 controls polarization and migration of murine cytotoxic T cells.
AB  - Midline 1 (MID1) is a microtubule-associated ubiquitin ligase that regulates
      protein phosphatase 2 A levels. Loss-of-function mutations in MID1 lead to the
      human X-linked Opitz G/BBB (OS) syndrome characterized by defective midline
      development during embryogenesis. We have recently shown that MID1 is strongly up
      regulated in murine cytotoxic T lymphocytes (CTLs), and that it has a significant
      impact on exocytosis of lytic granules and the killing capacity of CTLs. The aims
      of the present study were to determine the localization of MID1 in migrating
      CTLs, and to investigate whether MID1 affects CTL polarization and migration. We
      found that MID1 mainly localizes to the uropod of migrating CTLs and that it has
      a substantial impact on CTL polarization and migration in vitro. Furthermore,
      analysis of contact hypersensitivity responses supported that MID1 controls
      effector functions of CTLs in hapten-challenged skin in vivo. These results
      provide significant new knowledge on the role of MID1 in CTL biology. 

PMID- 25866635
TI  - Direct Toll-Like Receptor 8 signaling increases the functional avidity of human
      CD8+ T lymphocytes generated for adoptive T cell therapy strategies.
AB  - Adoptive transfer of in vitro activated and expanded antigen-specific cytotoxic T
      lymphocytes (CTLs) is a promising therapeutic strategy for infectious diseases
      and cancers. Obtaining in vitro a sufficient amount of highly specific cytotoxic
      cells and capable of retaining cytotoxic activity in vivo remains problematic. We
      studied the role of Toll-Like Receptor-8 (TLR8) engagement on peripheral CTLs
      activated with melanoma antigen MART-1-expressing artificial antigen-presenting
      cells (AAPCs). After a 3-week co-culture, 3-27% of specific CTLs were
      consistently obtained. CTLs expressed TLR8 in the intracellular compartment and
      at the cell surface. Specific CTLs activated with a TLR8 agonist (CL075) 24 h
      before the end of the culture displayed neither any change in their production
      levels of molecules involved in cytotoxicity (IFN-gamma, Granzyme B, and TNF
      alpha) nor major significant change in their cell surface phenotype. However,
      these TLR8-stimulated lymphocytes displayed increased cytotoxic activity against
      specific peptide-pulsed target cells related to an increase in specific anti
      melanoma CTL functional avidity. TLR8 engagement on CTLs could, therefore, be
      useful in different immunotherapy strategies. 

PMID- 25866636
TI  - A retrospective, cross-sectional study reveals that women with CRSwNP have more
      severe disease than men.
AB  - Up to 50% of patients with chronic rhinosinusitis (CRS) have comorbid asthma, and
      we have reported that a subset of CRS patients who have nasal polyps (CRSwNP)
      have elevated autoantigen-specific antibodies within their nasal polyps (NP).
      While increases in the prevalence and/or severity of both asthma and autoimmunity
      in women are well characterized, it is not known whether CRSwNP is more severe or
      frequent in women than men. We sought to determine whether CRSwNP demonstrated
      sex-specific differences in frequency and/or severity. Using a retrospectively
      collected database of tertiary care patients (n = 1393), we evaluated the
      distribution of sex in patients with CRSwNP with or without comorbid asthma or
      aspirin hypersensitivity. We further compared the severity of sinus disease
      between men and women with CRSwNP. Although women comprised 55% of CRS patients
      without NP (CRSsNP), a significantly smaller proportion of CRSwNP patients were
      female (38%, P < 0.001). Interestingly, women with CRSwNP were significantly more
      likely than men to have comorbid asthma (P < 0.001), and 61% of patients with the
      most severe form of disease (aspirin-exacerbated respiratory disease (CRSwNP plus
      asthma plus aspirin sensitivity)) were women (P < 0.05). Women with CRSwNP were
      significantly more likely to have taken oral steroids, and were more likely to
      have a history of revision surgeries (P < 0.05) compared to men. These data
      suggest that women with CRSwNP have more severe disease than men in a tertiary
      care setting. Future studies are needed to elucidate the mechanisms that drive
      disease severity in men and women, paving the way for the development of
      personalized treatment strategies for CRSwNP based on sex. 

PMID- 25866637
TI  - Serglycin is part of the secretory repertoire of LPS-activated monocytes.
AB  - Monocytes play multiple roles in the immune system, and are active in both acute
      and chronic diseases. Patients exposed to bacterial infections depend on
      monocytes in defense reactions, but excessive immune reactions may also cause
      morbidity through systemic inflammatory responses. Few studies have addressed the
      importance of proteoglycans, and in particular, the hematopoietic serglycin, in
      such monocyte immune reactions. Adherent primary monocytes were cultured in
      absence and presence of LPS. Media were analyzed by ELISA for detection of
      serglycin. Lysed cell fractions were used to determine the mRNA level of
      serglycin. Monocytes were also cultured on chamber slides to investigate if
      serglycin could be detected intracellularly by immunocytochemistry. Monocytes
      secreted serglycin, and LPS-stimulation increased the secretion. Secretion of
      inflammatory cytokines increased to a larger extent than serglycin. mRNA levels
      of serglycin were also increased, suggesting both increased expression and
      secretion. Immunocytochemistry revealed the presence of serglycin in
      intracellular vesicles, many destined for secretion. Serglycin containing
      vesicles increased in number and size when the cells were exposed to LPS.
      Intracellular vesicle localization and secretion of the proteoglycan serglycin is
      shown for the first time in primary human monocytes. Monocyte activation by LPS
      increased the expression and secretion of serglycin, suggesting roles for
      serglycin in inflammatory processes. 

PMID- 25866638
TI  - TSLP is differentially regulated by vitamin D3 and cytokines in human skin.
AB  - Thymic stromal lymphopoietin (TSLP) plays an important role in allergic diseases
      and is highly expressed in keratinocytes in human lesional atopic dermatitis (AD)
      skin. In nonlesional AD skin TSLP expression can be induced by applying house
      dust mite allergen onto the skin in the atopy patch test. Several studies have
      demonstrated that the induction of TSLP expression in mouse skin does not only
      lead to AD-like inflammation of the skin, but also predisposes to severe
      inflammation of the airways. In mice, TSLP expression can be induced by
      application of the 1,25-dihydroxyvitamin D3 (VD3) analogue calcipotriol and
      results in the development of eczema-like lesions. The objective is to
      investigate the effect of VD3 (calcitriol) or calcipotriol on TSLP expression in
      normal human skin and skin from AD patients. Using multiple ex vivo experimental
      setups, the effects of calci(po)triol on TSLP expression by normal human skin,
      and skin from AD patients were investigated and compared to effects of
      calcipotriol on mouse and non-human primates (NHP) skin. No induction of TSLP
      expression (mRNA or protein) was observed in human keratinocytes, normal human
      skin, nonlesional AD skin, or NHP skin samples after stimulation with
      calcipotriol or topical application of calcitriol. The biological activity of
      calci(po)triol in human skin samples was demonstrated by the increased expression
      of the VD3-responsive Cyp24a1 gene. TSLP expression was induced by cytokines (IL
      4, IL-13, and TNF-alpha) in skin samples from all three species. In contrast to
      the findings in human and NHP, a consistent increase in TSLP expression was
      confirmed in mouse skin biopsies after stimulation with calcipotriol. VD3 failed
      to induce expression of TSLP in human or monkey skin in contrast to mouse,
      implicating careful extrapolation of this often-used mouse model to AD patients. 

PMID- 25866640
TI  - Resolution improvement by 3D particle averaging in localization microscopy.
AB  - Inspired by recent developments in localization microscopy that applied averaging
      of identical particles in 2D for increasing the resolution even further, we
      discuss considerations for alignment (registration) methods for particles in
      general and for 3D in particular. We detail that traditional techniques for
      particle registration from cryo electron microscopy based on cross-correlation
      are not suitable, as the underlying image formation process is fundamentally
      different. We argue that only localizations, i.e. a set of coordinates with
      associated uncertainties, are recorded and not a continuous intensity
      distribution. We present a method that owes to this fact and that is inspired by
      the field of statistical pattern recognition. In particular we suggest to use an
      adapted version of the Bhattacharyya distance as a merit function for
      registration. We evaluate the method in simulations and demonstrate it on three
      dimensional super-resolution data of Alexa 647 labelled to the Nup133 protein in
      the nuclear pore complex of Hela cells. From the simulations we find suggestions
      that for successful registration the localization uncertainty must be smaller
      than the distance between labeling sites on a particle. These suggestions are
      supported by theoretical considerations concerning the attainable resolution in
      localization microscopy and its scaling behavior as a function of labeling
      density and localization precision.

PMID- 25866641
TI  - A genome wide association study on Newfoundland colorectal cancer patients'
      survival outcomes.
AB  - BACKGROUND: In this study we performed genome-wide association studies to
      identify candidate SNPs that may predict the risk of disease outcome in
      colorectal cancer. METHODS: Patient cohort consisted of 505 unrelated patients
      with Caucasian ancestry. Germline DNA samples were genotyped using the
      Illumina(r) human Omni-1quad SNP chip. Associations of SNPs with overall and
      disease free survivals were examined primarily for 431 patients with
      microsatellite instability-low (MSI-L) or stable (MSS) colorectal tumors using
      Cox proportional hazards method adjusting for clinical covariates. Bootstrap
      method was applied for internal validation of results. As exploratory analyses,
      association analyses for the colon (n = 334) and rectal (n = 171) cancer patients
      were also performed. RESULTS: As a result, there was no SNP that reached the
      genomewide significance levels (p < 5x10(-8)) in any of the analyses. A small
      number of genetic markers (n = 10) showed nominal associations (p <10(-6)) for
      MSS/MSI-L, colon, or rectal cancer patient groups. These markers were located in
      two non-coding RNA genes or intergenic regions and none were amino acid
      substituting polymorphisms. Bootstrap analysis for the MSS/MSI-L cohort data
      suggested the robustness of the observed nominal associations. CONCLUSIONS:
      Likely due to small number of patients, our study did not identify an acceptable
      level of association of SNPs with outcome in MSS/MSI-L, colon, or rectal cancer
      patients. A number of SNPs with sub-optimal p-values were, however, identified;
      these loci may be promising and examined in other larger-sized patient cohorts.

PMID- 25866642
TI  - Judiciary views on criminal behaviour and intention of offenders with high
      functioning autism.
AB  - PURPOSE: The purpose of this paper is to explore how judges perceive High
      Functioning Autistic Spectrum Disorders (hfASDs) and the disorders' effects on an
      offender's ability to formulate criminal intent and control behaviour.
      DESIGN/METHODOLOGY/APPROACH: Semi-structured interviews on topics related to
      offenders with hfASDs were conducted with 21 California Superior Court Judges. A
      coding scheme was developed and an iterative qualitative coding process was used
      for analysis. FINDINGS: Analysis yielded three major themes on how an hfASD
      diagnosis affects an offender's ability to regulate actions and criminal
      behaviour. Interviewed judges reported beliefs that hfASD offenders view the
      world in a different way and that much of their behaviour is not under their
      direct control. Judges reported these perceptions likely affect how they
      criminally process and make legal decisions regarding offenders with hfASDs.
      RESEARCH LIMITATIONS/IMPLICATIONS: The sample size was small and therefore no
      statistical significance can be drawn from results; findings cannot be applied to
      perceptions or experiences of the entire California Superior Court Judge
      population. ORIGINALITY/VALUE: Past academic research reports that individuals
      with hfASDs that offend often do so because of specific symptoms associated with
      the disorder. This presents a complex dilemma for the criminal justice system
      regarding how best to understand the disorder and process these offenders. This
      study and its findings aim to shed light on issues judges encounter in
      determining these offenders' responsibility and sentencing, in what ways this
      information might be integrated into judicial decision making, and areas where
      future research is needed.

PMID- 25866644
TI  - Polymyxin B-immobilized fiber column hemoperfusion mainly helps to constrict
      peripheral blood vessels in treatment for septic shock.
AB  - BACKGROUND: Polymyxin B-immobilized fiber column hemoperfusion (PMX) has been
      reported to be effective for patients with septic shock. It remains unclear,
      however, how the efficacy of PMX varies according to the characteristics and
      underlying conditions of the patients treated. The objective of the present study
      was to clarify the factors that result in clinical efficacy of PMX treatment.
      METHODS: We retrospectively investigated 78 consecutive patients with severe
      sepsis or septic shock who underwent PMX treatment. We reviewed the demographic
      data, routine biochemistry, microbiological data, infection focus, Acute
      Physiology and Chronic Health Evaluation (APACHE) II score, Sequential Organ
      Failure Assessment (SOFA) score, change in mean arterial pressure (MAP),
      inotropic score, vasopressor dependency index, plasma levels of endotoxin and
      lactate, PaO2/FIO2 ratio, and survival time. We also divided the patients into
      two groups for comparison, namely, those whose inotropic scores improved after
      PMX treatment (improvement group) and those whose inotropic scores did not
      improve (non-improvement group). RESULTS: The inotropic score and the vasopressor
      dependency index significantly decreased from 18.1 to 9.9 (p < 0.05) and from
      0.27 to 0.14 (p < 0.05), respectively, after PMX treatment in the overall study
      population, while no significant change in the PaO2/FIO2 ratio was observed (p =
      0.96). The inotropic score at pre-PMX treatment was significantly higher in the
      improvement group than in the non-improvement group (p < 0.01). The improvement
      of the PaO2/FIO2 ratio after PMX treatment was significant in the improvement
      group (p < 0.05). CONCLUSIONS: The improvement group's inotropic score was
      higher, because of peripheral blood vessels dilatation and requirement for more
      catecholamines. Therefore, our study suggests that PMX treatment is particularly
      useful for improving hemodynamics in septic shock patients with excessively
      dilated peripheral blood vessels.

PMID- 25866645
TI  - High-flow nasal cannula oxygen therapy in adults.
AB  - High-flow nasal cannula (HFNC) oxygen therapy comprises an air/oxygen blender, an
      active humidifier, a single heated circuit, and a nasal cannula. It delivers
      adequately heated and humidified medical gas at up to 60 L/min of flow and is
      considered to have a number of physiological effects: reduction of anatomical
      dead space, PEEP effect, constant fraction of inspired oxygen, and good
      humidification. While there have been no big randomized clinical trials, it has
      been gaining attention as an innovative respiratory support for critically ill
      patients. Most of the available data has been published in the neonatal field.
      Evidence with critically ill adults are poor; however, physicians apply it to a
      variety of patients with diverse underlying diseases: hypoxemic respiratory
      failure, acute exacerbation of chronic obstructive pulmonary disease, post
      extubation, pre-intubation oxygenation, sleep apnea, acute heart failure,
      patients with do-not-intubate order, and so on. Many published reports suggest
      that HFNC decreases breathing frequency and work of breathing and reduces needs
      of escalation of respiratory support in patients with diverse underlying
      diseases. Some important issues remain to be resolved, such as its indication,
      timing of starting and stopping HFNC, and escalating treatment. Despite these
      issues, HFNC oxygen therapy is an innovative and effective modality for the early
      treatment of adults with respiratory failure with diverse underlying diseases. 

PMID- 25866647
TI  - Hypothyroidism and non-cardiogenic pulmonary edema: are we missing something
      here?
AB  - We report the case of a 42-year-old female with a history of hypothyroidism and
      asthma presenting with progressive dyspnea and orthopnea after 2 days of an upper
      respiratory tract infection (URTI). Based on the clinical and radiological
      findings, the patient was admitted as a case of cardiogenic pulmonary edema
      secondary to possible viral myocarditis. However, a normal brain natriuretic
      peptide (BNP) level with a normal ejection fraction (EF) on echocardiogram
      changed our working diagnosis from cardiogenic to non-cardiogenic pulmonary
      edema. Further questioning revealed a history of nocturnal snoring, frequent
      awakening, and daytime fatigue, suggesting a possible sleep apnea syndrome (SAS).
      In conclusion, we believe that SAS was the missing link between our patient's
      hypothyroidism and non-cardiogenic pulmonary edema. LEARNING POINTS: Always keep
      an open mind and look for a pathology that would explain the whole clinical
      scenario.The involvement of the respiratory system in hypothyroidism can range
      from SAS, pulmonary hypertension, hypoventilation, and severe respiratory
      failure.Hypothyroidism and SAS should be considered in the differential diagnosis
      of non-cardiogenic pulmonary edema.Patients should be instructed to take
      levothyroxine on an empty stomach 30-60 min before food to avoid erratic
      absorption of the hormone.

PMID- 25866646
TI  - Venomous snake bites: clinical diagnosis and treatment.
AB  - Snake bites are life-threatening injuries that can require intensive care. The
      diagnosis and treatment of venomous snake bites is sometimes difficult for
      clinicians because sufficient information has not been provided in clinical
      practice. Here we review the literature to present the proper management of bites
      by mamushi, habu, and yamakagashi snakes, which widely inhabit Japan and other
      Asian countries. No definite diagnostic markers or kits are available for
      clinical practice; therefore, definitive diagnosis of snake-venom poisoning
      requires positive identification of the snake and observation of the clinical
      manifestations of envenomation. Mamushi (Gloydius blomhoffii) bites cause
      swelling and pain that spreads gradually from the bite site. The platelet count
      gradually decreases due to the platelet aggregation activity of the venom and can
      decrease to <100,000/mm(3). If the venom gets directly injected into the blood
      vessel, the platelet count rapidly decreases to <10,000/mm(3) within 1 h after
      the bite. Habu (Protobothrops flavoviridis) bites result in swelling within 30
      min. Severe cases manifest not only local signs but also general symptoms such as
      vomiting, cyanosis, loss of consciousness, and hypotension. Yamakagashi
      (Rhabdophis tigrinus) bites induce life-threatening hemorrhagic symptoms and
      severe disseminated intravascular coagulation with a fibrinolytic phenotype,
      resulting in hypofibrinogenemia and increased levels of fibrinogen degradation
      products. Previously recommended first-aid measures such as tourniquets,
      incision, and suction are strongly discouraged. Once airway, breathing, and
      circulation have been established, a rapid, detailed history should be obtained.
      If a snake bite is suspected, hospital admission should be considered for further
      follow-up. All venomous snake bites can be effectively treated with antivenom.
      Side effects of antivenom should be prevented by sufficient preparation. Approved
      antivenoms for mamushi and habu are available. Yamakagashi antivenom is used as
      an off-label drug in Japan, requiring clinicians to join a clinical research
      group for its use in clinical practice. 

PMID- 25866648
TI  - Biological crystallography: new methods, new challenges.
AB  - The ability of crystallography to illuminate biology and contribute to medical
      advances continues to grow. Recent advances expand its reach while also asking
      questions of its practitioners. 

PMID- 25866649
TI  - Intermolecular atom-atom bonds in crystals?
AB  - Some questions are raised concerning the interpretation of distances between
      atoms of neighbouring molecules in crystals. 

PMID- 25866650
TI  - Intermolecular atom-atom bonds in crystals - a chemical perspective.
AB  - Short atom-atom distances between molecules are almost always indicative of
      specific intermolecular bonding. These distances may be used to assess the
      significance of all hydrogen bonds, including the C-H?O and even weaker C-H?F
      varieties. 

PMID- 25866651
TI  - On atom-atom 'short contact' bonding interactions in crystals.
AB  - Professor Dunitz questions the usefulness of ascribing crystalline structural
      stability to individual atom-atom intermolecular interactions viewed as bonding
      (hence stabilizing) whenever linked by a bond path. An alternative view is
      expressed in the present essay that articulates the validity and usefulness of
      the bond path concept in a crystallographic and crystal engineering context. 

PMID- 25866652
TI  - Solving coiled-coil protein structures.
AB  - The successful approach to solving crystal structures of coiled-coil proteins
      with the program AMPLE is discussed. 

PMID- 25866653
TI  - Topochemical control in desolvation of coordination polymers.
AB  - Reactions in the solid state are at the core of crystal engineering as they can
      result in new crystalline phases that are not always accessible by traditional
      solution methods. The work of Brammer and co-workers [Wright et al. (2015),
      IUCrJ, 2, 188-197] represents a clear example of this potential as applied to the
      synthesis of a silver-phenazine coordination polymer. 

PMID- 25866654
TI  - Lipidic cubic phase serial millisecond crystallography using synchrotron
      radiation.
AB  - Lipidic cubic phases (LCPs) have emerged as successful matrixes for the
      crystallization of membrane proteins. Moreover, the viscous LCP also provides a
      highly effective delivery medium for serial femtosecond crystallography (SFX) at
      X-ray free-electron lasers (XFELs). Here, the adaptation of this technology to
      perform serial millisecond crystallography (SMX) at more widely available
      synchrotron microfocus beamlines is described. Compared with conventional
      microcrystallography, LCP-SMX eliminates the need for difficult handling of
      individual crystals and allows for data collection at room temperature. The
      technology is demonstrated by solving a structure of the light-driven proton-pump
      bacteriorhodopsin (bR) at a resolution of 2.4 A. The room-temperature structure
      of bR is very similar to previous cryogenic structures but shows small yet
      distinct differences in the retinal ligand and proton-transfer pathway. 

PMID- 25866655
TI  - Structure of a 13-fold superhelix (almost) determined from first principles.
AB  - Nuclear hormone receptors are cytoplasm-based transcription factors that bind a
      ligand, translate to the nucleus and initiate gene transcription in complex with
      a co-activator such as TIF2 (transcriptional intermediary factor 2). For
      structural studies the co-activator is usually mimicked by a peptide of circa 13
      residues, which for the largest part forms an alpha-helix when bound to the
      receptor. The aim was to co-crystallize the glucocorticoid receptor in complex
      with a ligand and the TIF2 co-activator peptide. The 1.82 A resolution
      diffraction data obtained from the crystal could not be phased by molecular
      replacement using the known receptor structures. HPLC analysis of the crystals
      revealed the absence of the receptor and indicated that only the co-activator
      peptide was present. The self-rotation function displayed 13-fold rotational
      symmetry, which initiated an exhaustive but unsuccessful molecular-replacement
      approach using motifs of 13-fold symmetry such as alpha- and beta-barrels in
      various geometries. The structure was ultimately determined by using a single
      alpha-helix and the software ARCIMBOLDO, which assembles fragments placed by
      PHASER before using them as seeds for density modification model building in
      SHELXE. Systematic variation of the helix length revealed upper and lower size
      limits for successful structure determination. A beautiful but unanticipated
      structure was obtained that forms superhelices with left-handed twist throughout
      the crystal, stabilized by ligand interactions. Together with the increasing
      diversity of structural elements in the Protein Data Bank the results from TIF2
      confirm the potential of fragment-based molecular replacement to significantly
      accelerate the phasing step for native diffraction data at around 2 A resolution.

PMID- 25866656
TI  - Solvent-vapour-assisted pathways and the role of pre-organization in solid-state
      transformations of coordination polymers.
AB  - A family of one-dimensional coordination polymers,
      [Ag4(O2C(CF2)2CF3)4(phenazine)2(arene) n ].m(arene), 1 (arene = toluene or
      xylene), have been synthesized and crystallographically characterized. Arene
      guest loss invokes structural transformations to yield a pair of polymorphic
      coordination polymers [Ag4(O2C(CF2)2CF3)4(phenazine)2], 2a and/or 2b , with one-
      and two-dimensional architectures, respectively. The role of pre-organization of
      the polymer chains of 1 in the selectivity for formation of either polymorph is
      explored, and the templating effect of toluene and p-xylene over o-xylene or m
      xylene in the formation of arene-containing architecture 1 is also demonstrated.
      The formation of arene-free phase 2b , not accessible in a phase-pure form
      through other means, is shown to be the sole product of loss of toluene from 1
      tol.tol [Ag4(O2C(CF2)2CF3)4(phenazine)2(toluene)].2(toluene), a phase containing
      toluene coordinated to Ag(I) in an unusual MU:eta(1),eta(1) manner. Solvent
      vapour-assisted conversion between the polymorphic coordination polymers and
      solvent-vapour influence on the conversion of coordination polymers 1 to 2a and
      2b is also explored. The transformations have been examined and confirmed by X
      ray diffraction, NMR spectroscopy and thermal analyses, including in situ
      diffraction studies of some transformations. 

PMID- 25866657
TI  - Routine phasing of coiled-coil protein crystal structures with AMPLE.
AB  - Coiled-coil protein folds are among the most abundant in nature. These folds
      consist of long wound alpha-helices and are architecturally simple, but
      paradoxically their crystallographic structures are notoriously difficult to
      solve with molecular-replacement techniques. The program AMPLE can solve crystal
      structures by molecular replacement using ab initio search models in the absence
      of an existent homologous protein structure. AMPLE has been benchmarked on a
      large and diverse test set of coiled-coil crystal structures and has been found
      to solve 80% of all cases. Successes included structures with chain lengths of up
      to 253 residues and resolutions down to 2.9 A, considerably extending the limits
      on size and resolution that are typically tractable by ab initio methodologies.
      The structures of two macromolecular complexes, one including DNA, were also
      successfully solved using their coiled-coil components. It is demonstrated that
      both the ab initio modelling and the use of ensemble search models contribute to
      the success of AMPLE by comparison with phasing attempts using single structures
      or ideal polyalanine helices. These successes suggest that molecular replacement
      with AMPLE should be the method of choice for the crystallo-graphic elucidation
      of a coiled-coil structure. Furthermore, AMPLE may be able to exploit the
      presence of a coiled coil in a complex to provide a convenient route for phasing.

PMID- 25866658
TI  - Advanced ensemble modelling of flexible macromolecules using X-ray solution
      scattering.
AB  - Dynamic ensembles of macromolecules mediate essential processes in biology.
      Understanding the mechanisms driving the function and molecular interactions of
      'unstructured' and flexible molecules requires alternative approaches to those
      traditionally employed in structural biology. Small-angle X-ray scattering (SAXS)
      is an established method for structural characterization of biological
      macromolecules in solution, and is directly applicable to the study of flexible
      systems such as intrinsically disordered proteins and multi-domain proteins with
      unstructured regions. The Ensemble Optimization Method (EOM) [Bernado et al.
      (2007 ?). J. Am. Chem. Soc. 129, 5656-5664] was the first approach introducing
      the concept of ensemble fitting of the SAXS data from flexible systems. In this
      approach, a large pool of macromolecules covering the available conformational
      space is generated and a sub-ensemble of conformers coexisting in solution is
      selected guided by the fit to the experimental SAXS data. This paper presents a
      series of new developments and advancements to the method, including
      significantly enhanced functionality and also quantitative metrics for the
      characterization of the results. Building on the original concept of ensemble
      optimization, the algorithms for pool generation have been redesigned to allow
      for the construction of partially or completely symmetric oligomeric models, and
      the selection procedure was improved to refine the size of the ensemble.
      Quantitative measures of the flexibility of the system studied, based on the
      characteristic integral parameters of the selected ensemble, are introduced.
      These improvements are implemented in the new EOM version 2.0, and the
      capabilities as well as inherent limitations of the ensemble approach in SAXS,
      and of EOM 2.0 in particular, are discussed. 

PMID- 25866659
TI  - High-pressure crystallography of periodic and aperiodic crystals.
AB  - More than five decades have passed since the first single-crystal X-ray
      diffraction experiments at high pressure were performed. These studies were
      applied historically to geochemical processes occurring in the Earth and other
      planets, but high-pressure crystallography has spread across different fields of
      science including chemistry, physics, biology, materials science and pharmacy.
      With each passing year, high-pressure studies have become more precise and
      comprehensive because of the development of instrumentation and software, and the
      systems investigated have also become more complicated. Starting with crystals of
      simple minerals and inorganic compounds, the interests of researchers have
      shifted to complicated metal-organic frameworks, aperiodic crystals and
      quasicrystals, molecular crystals, and even proteins and viruses. Inspired by
      contributions to the microsymposium 'High-Pressure Crystallography of Periodic
      and Aperiodic Crystals' presented at the 23rd IUCr Congress and General Assembly,
      the authors have tried to summarize certain recent results of single-crystal
      studies of molecular and aperiodic structures under high pressure. While the
      selected contributions do not cover the whole spectrum of high-pressure research,
      they demonstrate the broad diversity of novel and fascinating results and may
      awaken the reader's interest in this topic. 

PMID- 25866660
TI  - The potential of future light sources to explore the structure and function of
      matter.
AB  - Structural studies in general, and crystallography in particular, have benefited
      and still do benefit dramatically from the use of synchrotron radiation. Low
      emittance storage rings of the third generation provide focused beams down to the
      micrometre range that are sufficiently intense for the investigation of weakly
      scattering crystals down to the size of several micrometres. Even though the
      coherent fraction of these sources is below 1%, a number of new imaging
      techniques have been developed to exploit the partially coherent radiation.
      However, many techniques in nanoscience are limited by this rather small coherent
      fraction. On the one hand, this restriction limits the ability to study the
      structure and dynamics of non-crystalline materials by methods that depend on the
      coherence properties of the beam, like coherent diffractive imaging and X-ray
      correlation spectroscopy. On the other hand, the flux in an ultra-small
      diffraction-limited focus is limited as well for the same reason. Meanwhile, new
      storage rings with more advanced lattice designs are under construction or under
      consideration, which will have significantly smaller emittances. These sources
      are targeted towards the diffraction limit in the X-ray regime and will provide
      roughly one to two orders of magnitude higher spectral brightness and coherence.
      They will be especially suited to experiments exploiting the coherence properties
      of the beams and to ultra-small focal spot sizes in the regime of several
      nanometres. Although the length of individual X-ray pulses at a storage-ring
      source is of the order of 100 ps, which is sufficiently short to track structural
      changes of larger groups, faster processes as they occur during vision or
      photosynthesis, for example, are not accessible in all details under these
      conditions. Linear accelerator (linac) driven free-electron laser (FEL) sources
      with extremely short and intense pulses of very high coherence circumvent some of
      the limitations of present-day storage-ring sources. It has been demonstrated
      that their individual pulses are short enough to outrun radiation damage for
      single-pulse exposures. These ultra-short pulses also enable time-resolved
      studies 1000 times faster than at standard storage-ring sources. Developments are
      ongoing at various places for a totally new type of X-ray source combining a
      linac with a storage ring. These energy-recovery linacs promise to provide pulses
      almost as short as a FEL, with brilliances and multi-user capabilities comparable
      with a diffraction-limited storage ring. Altogether, these new X-ray source
      developments will provide smaller and more intense X-ray beams with a
      considerably higher coherent fraction, enabling a broad spectrum of new
      techniques for studying the structure of crystalline and non-crystalline states
      of matter at atomic length scales. In addition, the short X-ray pulses of FELs
      will enable the study of fast atomic dynamics and non-equilibrium states of
      matter. 

PMID- 25866661
TI  - Serial femtosecond crystallography: the first five years.
AB  - Protein crystallography using synchrotron radiation sources has had a tremendous
      impact on biology, having yielded the structures of thousands of proteins and
      given detailed insight into their mechanisms. However, the technique is limited
      by the requirement for macroscopic crystals, which can be difficult to obtain, as
      well as by the often severe radiation damage caused in diffraction experiments,
      in particular when using tiny crystals. To slow radiation damage, data collection
      is typically performed at cryogenic temperatures. With the advent of free
      electron lasers (FELs) capable of delivering extremely intense femtosecond X-ray
      pulses, this situation appears to be remedied, allowing the structure
      determination of undamaged macromolecules using either macroscopic or microscopic
      crystals. The latter are exposed to the FEL beam in random orientations and their
      diffraction data are collected at cryogenic or room temperature in a serial
      fashion, since each crystal is destroyed upon a single exposure. The new
      approaches required for crystal growth and delivery, and for diffraction data
      analysis, including de novo phasing, are reviewed. The opportunities and
      challenges of SFX are described, including applications such as time-resolved
      measurements and the analysis of radiation damage-prone systems. 

PMID- 25866662
TI  - Metadynamics studies of crystal nucleation.
AB  - Crystallization processes are characterized by activated events and long
      timescales. These characteristics prevent standard molecular dynamics techniques
      from being efficiently used for the direct investigation of processes such as
      nucleation. This short review provides an overview on the use of metadynamics, a
      state-of-the-art enhanced sampling technique, for the simulation of phase
      transitions involving the production of a crystalline solid. In particular the
      principles of metadynamics are outlined, several order parameters are described
      that have been or could be used in conjunction with metadynamics to sample
      nucleation events and then an overview is given of recent metadynamics results in
      the field of crystal nucleation. 

PMID- 25866663
TI  - Three-dimensional electron diffraction as a complementary technique to powder X
      ray diffraction for phase identification and structure solution of powders.
AB  - Phase identification and structure determination are important and widely used
      techniques in chemistry, physics and materials science. Recently, two methods for
      automated three-dimensional electron diffraction (ED) data collection, namely
      automated diffraction tomography (ADT) and rotation electron diffraction (RED),
      have been developed. Compared with X-ray diffraction (XRD) and two-dimensional
      zonal ED, three-dimensional ED methods have many advantages in identifying phases
      and determining unknown structures. Almost complete three-dimensional ED data can
      be collected using the ADT and RED methods. Since each ED pattern is usually
      measured off the zone axes by three-dimensional ED methods, dynamic effects are
      much reduced compared with zonal ED patterns. Data collection is easy and fast,
      and can start at any arbitrary orientation of the crystal, which facilitates
      automation. Three-dimensional ED is a powerful technique for structure
      identification and structure solution from individual nano- or micron-sized
      particles, while powder X-ray diffraction (PXRD) provides information from all
      phases present in a sample. ED suffers from dynamic scattering, while PXRD data
      are kinematic. Three-dimensional ED methods and PXRD are complementary and their
      combinations are promising for studying multiphase samples and complicated
      crystal structures. Here, two three-dimensional ED methods, ADT and RED, are
      described. Examples are given of combinations of three-dimensional ED methods and
      PXRD for phase identification and structure determination over a large number of
      different materials, from Ni-Se-O-Cl crystals, zeolites, germanates, metal
      organic frameworks and organic compounds to intermetallics with modulated
      structures. It is shown that three-dimensional ED is now as feasible as X-ray
      diffraction for phase identification and structure solution, but still needs
      further development in order to be as accurate as X-ray diffraction. It is
      expected that three-dimensional ED methods will become crucially important in the
      near future. 

PMID- 25866664
TI  - Synchrotron radiation macromolecular crystallography: science and spin-offs.
AB  - A current overview of synchrotron radiation (SR) in macromolecular
      crystallography (MX) instrumentation, methods and applications is presented.
      Automation has been and remains a central development in the last decade, as have
      the rise of remote access and of industrial service provision. Results include a
      high number of Protein Data Bank depositions, with an increasing emphasis on the
      successful use of microcrystals. One future emphasis involves pushing the
      frontiers of using higher and lower photon energies. With the advent of X-ray
      free-electron lasers, closely linked to SR developments, the use of ever smaller
      samples such as nanocrystals, nanoclusters and single molecules is anticipated,
      as well as the opening up of femtosecond time-resolved diffraction structural
      studies. At SR sources, a very high-throughput assessment for the best crystal
      samples and the ability to tackle just a few micron and sub-micron crystals will
      become widespread. With higher speeds and larger detectors, diffraction data
      volumes are becoming long-term storage and archiving issues; the implications for
      today and the future are discussed. Together with the rise of the storage ring to
      its current pre-eminence in MX data provision, the growing tendency of central
      facility sites to offer other centralized facilities complementary to
      crystallography, such as cryo-electron microscopy and NMR, is a welcome
      development. 

PMID- 25866665
TI  - Functional materials analysis using in situ and in operando X-ray and neutron
      scattering.
AB  - In situ and in operando studies are commonplace and necessary in functional
      materials research. This review highlights recent developments in the analysis of
      functional materials using state-of-the-art in situ and in operando X-ray and
      neutron scattering and analysis. Examples are given covering a number of
      important materials areas, alongside a description of the types of information
      that can be obtained and the experimental setups used to acquire them. 

PMID- 25866666
TI  - Public-health impact of outdoor air pollution for 2(nd) air pollution management
      policy in Seoul metropolitan area, Korea.
AB  - OBJECTIVES: Air pollution contributes to mortality and morbidity. We estimated
      the impact of outdoor air pollution on public health in Seoul metropolitan area,
      Korea. Attributable cases of morbidity and mortality were estimated. METHODS:
      Epidemiology-based exposure-response functions for a 10 MUg/m3 increase in
      particulate matter (PM2.5 and PM10) were used to quantify the effects of air
      pollution. Cases attributable to air pollution were estimated for mortality
      (adults >= 30 years), respiratory and cardiovascular hospital admissions (all
      ages), chronic bronchitis (all ages), and acute bronchitis episodes (<=18 years).
      Environmental exposure (PM2.5 and PM10) was modeled for each 3 km * 3 km.
      RESULTS: In 2010, air pollution caused 15.9% of total mortality or approximately
      15,346 attributable cases per year. Particulate air pollution also accounted for:
      12,511 hospitalized cases of respiratory disease; 20,490 new cases of chronic
      bronchitis (adults); 278,346 episodes of acute bronchitis (children). After
      performing the 2(nd) Seoul metropolitan air pollution management plan, the
      reducible death number associated with air pollution is 14,915 cases per year in
      2024. We can reduce 57.9% of death associated with air pollution. CONCLUSION:
      This assessment estimates the public-health impacts of current patterns of air
      pollution. Although individual health risks of air pollution are relatively
      small, the public-health consequences are remarkable. Particulate air pollution
      remains a key target for public-health action in the Seoul metropolitan area. Our
      results, which have also been used for economic valuation, should guide decisions
      on the assessment of environmental health-policy options.

PMID- 25866667
TI  - Effect of maternal job strain during pregnancy on infant neurodevelopment by
      gender at 6 and 12 months: Mothers and Children's Environmental Health (MOCEH)
      study.
AB  - OBJECTIVES: Limited evidence is available regarding the association between
      prenatal job strain and infant neurodevelopment. Most studies used stress
      indicators other than job strain to explain the relationship between prenatal
      maternal stress and child development. The objective of this study was to
      investigate the association between maternal job strain during pregnancy and
      neurodevelopment in infancy. METHODS: Mothers and Children's Environmental Health
      (MOCEH) study, an on-going prospective birth cohort study, has been conducted in
      South Korea since 2006. Job strain during pregnancy was measured using Korean
      version of Job Content Questionnaire (JCQ). Infant neurodevelopment was assessed
      using Korean Bayley Scale of Infant Development II (K-BSID-II) at 6 and 12 months
      of age. A total of 343 mother-child pairs that completed JCQ and K-BSID-II more
      than once were included. Mental Developmental Index (MDI) and Psychomotor
      Developmental Index (PDI) defined in the K-BSID-II were used as outcome
      variables. RESULTS: Compared to infants from mothers with low job strain,
      significant (p < 0.05) decreases in PDI were found in infants from mothers with
      active and passive job at 6 months of age. After stratification by infant sex,
      boys in the high strain group had a lower MDI score than boys in the low job
      strain group at 12 months. On the other hand, girls in the high strain and active
      groups had higher MDI scores than girls in the low job strain group at 12 months.
      PDI at 12 months also showed different results by sex. Boys in the high strain
      and passive job groups had lower PDI scores than boys in the low job strain
      group. However, such difference was not observed in girls. CONCLUSIONS: The
      findings of this study suggest that prenatal job strain affects infant
      neurodevelopment in a gender-dependent manner.

PMID- 25866668
TI  - Work-related ocular events among Nigerian dental surgeons.
AB  - OBJECTIVE: Daily clinical activities in dental operatory expose dental surgeons
      to varied forms of ocular events. The purpose of the study was to determine the
      prevalence and pattern of ocular splashes and foreign bodies among dental
      surgeons in Nigeria. METHODS: This questionnaire-based cross-sectional of dental
      surgeons in Southern Nigeria was conducted between September 2010 and August
      2011. The information elicited were demography, experience and type of ocular
      event, implicated dental procedure and action taken. RESULTS: Of the 185 studied,
      148 of them responded. Of these 148 respondents, 56 (37.8%) reported foreign
      body, 18 (12.2%) splash, 33 (22.3%) both foreign body and splash while 41 (27.7%)
      reported no ocular event. It therefore means that the overall prevalence of
      ocular events among the respondents was 107 (72.3%). The prevalence of ocular
      events was significantly associated with age (p = 0.014), years of practice (p =
      0.033) and safety eye goggle use (p = 0.023). The main dental procedures
      implicated in the ocular events among the respondents were scaling 77 (72.0%),
      tooth/cavity preparation 17 (15.9%), polishing 11 (10.3%) and forcep tooth
      extraction 10 (9.3%). The major implicated aetiological agents in the ocular
      events were calculus 74 (69.2%), saliva 29 (27.1%), mixed blood & saliva 19
      (17.8%), tooth particles 15 (14.0%) and blood 9 (8.4%). The predominant action
      taken by the respondents was to rinse the eye under running water 89 (83.2%).
      CONCLUSION: Ocular splash and foreign body events are high among dental surgeons
      in Nigeria. Age, years of practice and safety eye goggles wear were also found to
      be associated with ocular events. Eye safety awareness is therefore deemed a
      necessity for dental surgeon in Southern Nigeria.

PMID- 25866669
TI  - Are clinical risk scores for COPD useful?

PMID- 25866670
TI  - Dialogue: A blissful future for lupus nephritis: harnessing repeat kidney
      biopsies to identify meaningful biomarkers of disease.

PMID- 25866671
TI  - Dialogue: Cutaneous lupus erythematosus: a lone Wolf?

PMID- 25866672
TI  - The Relationship between Estimated Glomerular Filtration Rate and Diabetic
      Retinopathy.
AB  - Diabetic retinopathy (DR) is the leading cause of visual impairment and blindness
      in working-aged people. Several studies have suggested that glomerular filtration
      rate (GFR) was correlated with DR. This is a hospital-based study and the aim of
      it was to examine the relationship between the GFR and DR in patients with type 2
      diabetes mellitus (T2DM). We used CKD-EPI equation to estimate GFR and SPSS 19.0
      and EmpowerStats software to assess their relationship. Among the 1613
      participants (aged 54.75 +/- 12.19 years), 550 (34.1%) patients suffered from DR.
      The multivariate analysis revealed that the risk factors for DR include age (P <
      0.001, OR = 0.940), duration of diabetes (P < 0.001, OR = 1.163), hemoglobin A1c
      (P = 0.007, OR = 1.224), systolic blood pressure (P < 0.001, OR = 1.032),
      diastolic blood pressure (P = 0.007, OR = 0.953), high density lipoprotein
      cholesterol (P = 0.024, OR = 3.884), and eGFR (P = 0.010, OR = 0.973). Through
      stratified analysis and saturation effect analysis, our data suggests that eGFR
      of 99.4 mL/min or lower might imply the early stage of DR in diabetic patients.
      Thus, the evaluation of eGFR has clinical significance for the early diagnosis of
      DR. 

PMID- 25866673
TI  - Surgical outcome of medial rectus resection in recurrent exotropia: a novel
      surgical formula.
AB  - Purpose. To evaluate the surgical outcomes of unilateral or bilateral medial
      rectus (MR) muscle resection for recurrent exotropia after bilateral lateral
      rectus (BLR) muscle recession based on a novel surgical formula. Methods. Forty
      one consecutive patients with unilateral or bilateral MR muscle resection for
      recurrent exotropia after BLR muscle recession were included in this
      retrospective study. All surgeries were performed according to the formula: 1.0
      mm MR muscle resection for every 5 prism dioptres (PD) of exotropia, with an
      addition of 0.5 mm to each MR muscle operated on. Results. The mean recurrent
      exotropia distant deviation was 28 PD +/- 11.2 (range 14 to 55 PD). Overall at
      postoperative 1 month, 36 (88%) achieved successful outcomes, 4 (10%) had
      undercorrection, and 1 (2%) had overcorrection. At postoperative 6 months, 29
      (71%) achieved successful outcomes, 12 (29%) had undercorrection, and none had
      overcorrection. Subgroup analysis showed no statistically significant difference
      in success rates between unilateral and bilateral MR groups. Conclusion.
      Unilateral or bilateral MR muscle resection using our surgical formula is a safe
      and effective method for calculating the amount of MR resection in moderate to
      large angle recurrent exotropia, with a low overcorrection rate. 

PMID- 25866674
TI  - The impact of incarceration on obesity: are prisoners with chronic diseases
      becoming overweight and obese during their confinement?
AB  - INTRODUCTION: The association between incarceration and weight gain, along with
      the public health impact of former prisoners who are overweight or obese,
      warrants more investigation to understand the impact of prison life. Studies
      regarding incarceration's impact on obesity are too few to support assertions
      that prisons contribute to obesity and comorbid conditions. This study examined a
      statewide prison population over several years to determine weight gain. METHODS:
      Objective data for weight, height, and chronic diseases, along with demographics,
      were extracted from an electronic health record. These data were analyzed
      statistically to determine changes over time and between groups. RESULTS: As a
      total population, prisoners not only gained weight, but also reflected the
      distribution of BMIs for the state. There were differences within the population.
      Male prisoners gained significantly less weight than females. The population with
      chronic diseases gained less weight than the population without comorbid
      conditions. Prisoners with diabetes lost weight while hypertension's impact was
      negligible. CONCLUSION: This study found that weight gain was a problem
      specifically to females. However, this prison system appears to be providing
      effective chronic disease management, particularly for prisoners with diabetes
      and hypertension. Additional research is needed to understand the impact
      incarceration has on the female population.

PMID- 25866675
TI  - Barriers to implementation of evidence based practice in zahedan teaching
      hospitals, iran, 2014.
AB  - This study aimed to determine the barriers to implementation of EBP among nurses.
      This cross-sectional study was conducted in Zahedan City, South East of Iran, in
      2014. The questionnaire of barriers to implementation of EBP consists of 27
      statements which was distributed among 280 nurses. More than half of the
      participants agreed that 56% and 57% of barriers to implementation of evidence
      based practice are related to organizational and individual aspects,
      respectively. Participants identified barriers at organizational level included
      the lack of human resources (78.3%), lack of internet access at work (72.2%), and
      heavy workload (70.0%). Barrier at individual level included lack of time to read
      literature (83.7%), lack of ability to work with computer (68.8%), and
      insufficient proficiency in English language (62.0%). Age, educational level, job
      experience, and employment status were associated with organizational barriers to
      implementation of EBP. At the individual level only education was associated with
      barriers to implementation of EBP. Barriers to implementation of EBP occur at
      both individual and organizational levels. The indicator of quality in nursing
      practice is EBP. Hence, familiarity with EBP is recommended for Iranian nurses.
      In addition, knowledge of barriers will help health care system and policy makers
      to provide a culture of EBP. 

PMID- 25866676
TI  - Maternal health coping strategies of migrant women in norway.
AB  - The aim of the study was to explore the maternal health coping strategies of
      migrant women in Norway. The ethnic and cultural background of the Norwegian
      population have become increasingly diverse. A challenge in practice is to adjust
      maternal health services to migrant women's specific needs. Previous studies have
      revealed that migrant women have difficulty achieving safe pregnancies and
      childbirths. Data were obtained by means of 17 semistructured interviews with
      women from South America, Europe, the Middle East, Asia, and Africa. Qualitative
      content analysis was employed. One overall theme is as follows: keeping original
      traditions while at the same time being willing to integrate into Norwegian
      society, and four themes emerged as follows: balancing their sense of
      belongingness; seeking information and support from healthcare professionals;
      being open to new opportunities and focusing on feeling safe in the new country.
      The results were interpreted in the light of Bronfenbrenner's ecological model.
      To provide quality care, healthcare professionals should focus on the development
      of migrant women's capabilities. Adaptation of maternal health services for
      culturally diverse migrant women also requires a culturally sensitive approach on
      the part of healthcare professionals. 

PMID- 25866677
TI  - Determinants of Pulmonary Tuberculosis among Inmates at Mangaung Maximum
      Correctional Facility in Bloemfontein, South Africa.
AB  - Introduction. Correctional facilities house large number of inmates who are at
      high risk of developing tuberculosis (TB); however factors associated with TB
      among inmates at Mangaung Correctional Centre have not been studied. Study
      Population and Methods. We undertook a case control study and reviewed a total of
      1140 medical records of inmates treated for TB between 2009 and 2010. Cases were
      selected randomly from the medical records of inmates who were treated. Data
      collected were analysed using STATA version 12.0 and determinants of TB were
      evaluated using multiple logistic regression analyses. Factors with P < 0.05 were
      considered significant. Results. Prevalence of TB was 8.8% and 52% of inmates
      with TB were aged 31-40 years; 58% of the TB cases were HIV positive and 34% of
      them had CD4 cell count 350 cells/mm(3). Factors associated with TB among inmates
      were HIV coinfection (OR: 4.2; 95% CI: 2.64-7.00); previous history of TB disease
      (OR: 3.58; 95% CI: 2.25-5.70); and smoking (OR: 2.1; 95% CI: 1.16-3.81).
      Conclusion. Interventions to improve TB detection such as regular screening of
      inmates with such factors need to be reinforced to control transmission of TB
      among inmates and the community. 

PMID- 25866678
TI  - Immunohistological analysis of the jun family and the signal transducers and
      activators of transcription in thymus.
AB  - The Jun family and the signal transducers and activators of transcription (STAT)
      are involved in proliferation and apoptosis. Moreover, c-Jun and STAT3 cooperate
      to regulate apoptosis. Therefore, we used double immunostaining to investigate
      the immunotopographical distribution of phospho-c-Jun (p-c-Jun), JunB, JunD, p
      STAT3, p-STAT5, and p-STAT6 in human thymus. JunD was frequently expressed by
      thymocytes with higher expression in medullary compared to cortical thymocytes. p
      c-Jun was frequently expressed by cortical and medullary thymic epithelial cells
      (TEC) and Hassall bodies (HB). p-STAT3 was frequently expressed by TEC with
      higher expression in cortical compared to medullary TEC and HB. p-c-Jun, JunB, p
      STAT3, p-STAT5, and p-STAT6 were rarely expressed by thymocytes. JunB and JunD
      were expressed by rare cortical TEC with higher expression in medullary TEC. p
      STAT5 and p-STAT6 were expressed by rare cortical and medullary TEC. Double
      immunostaining revealed p-c-Jun and JunD expression in rare CD11c positive
      dendritic cells. Our findings suggest a notable implication of JunD in the
      physiology of thymocytes and p-c-Jun and p-STAT3 in the physiology of TEC. The
      diversity of the immunotopographical distribution and the expression levels of p
      c-Jun, JunB, JunD, p-STAT3, p-STAT5, and p-STAT6 indicates that they are
      differentially involved in the differentiation of TEC, thymocytes, and dendritic
      cells. 

PMID- 25866679
TI  - Caspase Activation and Aberrant Cell Growth in a p53(+/+) Cell Line from a Li
      Fraumeni Syndrome Family.
AB  - Wild-type p53 is well known to induce cell cycle arrest and apoptosis to block
      aberrant cell growth. However, p53's unique role in apoptosis and cell
      proliferation in Li-Fraumeni Syndrome (LFS) has not been well elucidated. The aim
      of this study is to characterize the activity of wild-type p53 protein in LFS
      family dominated by a germline negative mutant p53. As expected, etoposide
      treated wild-type p53-containing cell lines, LFS 2852 and control Jurkat, showed
      a greater rate of caspase- and annexin V-induced apoptotic cell death compared to
      the p53-mutant LFS 2673 cell line although mitochondrial and nuclear assays could
      not detect apoptosis in these organelles. The most intriguing part of the
      observation was the abnormal proliferation rate of the wild-type p53-containing
      cell line, which grew twice as fast as 2673 and Jurkat cells. This is important
      because apoptosis inducers acting through the mitochondrial death pathway are
      emerging as promising drugs against tumors where the role of p53 is not only to
      target gene regulation but also to block cell proliferation. This study casts a
      long shadow on the possible dysregulation of p53 mediators that enable cell
      proliferation. The deregulation of proliferation pathways represents an important
      anticancer therapeutic strategy for patients with the LFS phenotype. 

PMID- 25866680
TI  - The reduction of distress using therapeutic geothermal water procedures in a
      randomized controlled clinical trial.
AB  - Stress is an element of each human's life and an indicator of its quality.
      Thermal mineral waters have been used empirically for the treatment of different
      diseases for centuries. Aim of the Study. To investigate the effects of highly
      mineralised geothermal water balneotherapy on distress and health risk.
      Methodology. A randomized controlled clinical trial was performed with 130
      seafarers: 65 underwent 2 weeks of balneotherapy with 108 g/L full-mineralisation
      bath treatment; the others were in control group. The effect of distress was
      measured using the General Symptoms Distress Scale. Factorial and logistic
      regression analyses were used for statistical analysis. Results. A significant
      positive effect on distress (P < 0.001) was established after 2 weeks of
      treatment: the number of stress symptoms declined by 60%, while the intensity of
      stress symptoms reduced by 41%, and the control improved by 32%. Health risks
      caused by distress were reduced, and resources increased, whereas the probability
      of general health risk decreased by 18% (P = 0.01). Conclusion. Balneotherapy
      with highly mineralised geothermal water reduces distress, by reducing the health
      risk posed by distress by 26%, increasing the health resources by 11%, and
      reducing probability of general health risk by 18%. Balneotherapy is an effective
      preventive tool and can take a significant place in integrative medicine. 

PMID- 25866682
TI  - Reconciling homeostatic and use-dependent plasticity in the context of
      somatosensory deprivation.
AB  - The concept of homeostatic plasticity postulates that neurons maintain relatively
      stable rates of firing despite changing inputs. Homeostatic and use-dependent
      plasticity mechanisms operate concurrently, although they have different
      requirements for induction. Depriving central somatosensory neurons of their
      primary activating inputs reduces activity and results in compensatory changes
      that favor excitation. Both a reduction of GABAergic inhibition and increase in
      glutamatergic excitatory transmission are observed in input-deprived cortex.
      Topographic reorganization of the adult somatosensory cortex is likely driven by
      both homeostatic and use-dependent mechanisms. Plasticity is induced by changes
      in the strengths of synaptic inputs, as well as changes in temporal correlation
      of neuronal activity. However, there is less certainty regarding the in vivo
      contribution of homeostatic mechanisms as in vitro experiments rely on
      manipulations that create states that do not normally occur in the living nervous
      system. Homeostatic plasticity seems to occur, but more in vivo research is
      needed to determine mechanisms. In vitro research is also needed but should
      better conform to conditions that might occur naturally in vivo. 

PMID- 25866684
TI  - A case of coronary vasospasm after repeat rituximab infusion.
AB  - Coronary artery vasospasm (CAV) can be triggered by medication reactions. CAV
      occurring after multiple exposures to rituximab has not been previously
      described. A 61-year-old woman with no cardiac risk factors was treated with the
      sixth cycle of gemcitabine, cisplatin, dexamethasone, and rituximab therapy.
      Fifteen minutes after rituximab infusion commenced, she developed typical cardiac
      chest pain with ST segment elevations on electrocardiogram. Angiogram revealed
      evidence of coronary vasospasm. The patient was successfully treated with
      amlodipine. This case underlines the importance of monitoring cardiac side
      effects of rituximab therapy, even after multiple cycles. 

PMID- 25866683
TI  - Efficacy and interindividual variability in motor-cortex plasticity following
      anodal tDCS and paired-associative stimulation.
AB  - Interindividual response variability to various motor-cortex stimulation
      protocols has been recently reported. Comparative data of stimulation protocols
      with different modes of action is lacking. We aimed to compare the efficacy and
      response variability of two LTP-inducing stimulation protocols in the human motor
      cortex: anodal transcranial direct current stimulation (a-tDCS) and paired
      associative stimulation (PAS25). In two experiments 30 subjects received 1mA a
      tDCS and PAS25. Data analysis focused on motor-cortex excitability change and
      response defined as increase in MEP applying different cut-offs. Furthermore, the
      predictive pattern of baseline characteristics was explored. Both protocols
      induced a significant increase in motor-cortical excitability. In the PAS25
      experiments the likelihood to develop a MEP response was higher compared to a
      tDCS, whereas for intracortical facilitation (ICF) the likelihood for a response
      was higher in the a-tDCS experiments. Baseline ICF (12 ms) correlated positively
      with an increase in MEPs only following a-tDCS and responders had significantly
      higher ICF baseline values. Contrary to recent studies, we showed significant
      group-level efficacy following both stimulation protocols confirming older
      studies. However, we also observed a remarkable amount of nonresponders. Our
      findings highlight the need to define sufficient physiological read-outs for a
      given plasticity protocol and to develop predictive markers for targeted
      stimulation.

PMID- 25866681
TI  - In vitro studies of neuronal networks and synaptic plasticity in invertebrates
      and in mammals using multielectrode arrays.
AB  - Brain functions are strictly dependent on neural connections formed during
      development and modified during life. The cellular and molecular mechanisms
      underlying synaptogenesis and plastic changes involved in learning and memory
      have been analyzed in detail in simple animals such as invertebrates and in
      circuits of mammalian brains mainly by intracellular recordings of neuronal
      activity. In the last decades, the evolution of techniques such as microelectrode
      arrays (MEAs) that allow simultaneous, long-lasting, noninvasive, extracellular
      recordings from a large number of neurons has proven very useful to study long
      term processes in neuronal networks in vivo and in vitro. In this work, we start
      off by briefly reviewing the microelectrode array technology and the optimization
      of the coupling between neurons and microtransducers to detect subthreshold
      synaptic signals. Then, we report MEA studies of circuit formation and activity
      in invertebrate models such as Lymnaea, Aplysia, and Helix. In the following
      sections, we analyze plasticity and connectivity in cultures of mammalian
      dissociated neurons, focusing on spontaneous activity and electrical stimulation.
      We conclude by discussing plasticity in closed-loop experiments. 

PMID- 25866685
TI  - Nelarabine associated myotoxicity and rhabdomyolysis.
AB  - Nelarabine (ara-G; Arranon; compound 506U78) is an antineoplastic purine analog
      used for the treatment of refractory or relapsed T-cell acute lymphoblastic
      leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL). The drug was granted
      accelerated approval in October 2005 by the US Food and Drug Administration (FDA)
      given the efficacy (induction of complete responses) noted in 2 single-arm trials
      (one in pediatric setting and one in adult patient population). The main spectra
      of toxicities that have been reported in these clinical trials and subsequent
      studies are hematological and neurological. Nelarabine induced rhabdomyolysis and
      increased creatinine phosphokinase (CK; CPK) levels apparently have been reported
      and this side effect has been added as an adverse reaction in the product
      monograph from the drug company during postmarketing surveillance. However, the
      true extent and incidence of the myotoxicity from the drug are unclear. In this
      paper we report a grade IV CK elevation and rhabdomyolysis in a patient with T
      ALL treated with nelarabine. Given the reported finding, we examined the
      literature further for myotoxicity, increased CK, and/or rhabdomyolysis
      associated with the use of the nelarabine and report our findings. 

PMID- 25866687
TI  - A Novel Mycobacterium cosmeticum-Like Bacterium Isolated from the Ear Swab of a
      Patient with Otitis Externa.
AB  - We describe the identification and characterization of a novel nontuberculous
      mycobacterium (NTM), isolated from an ear swab of an adult male patient with
      chronic otitis externa. Genetically, the bacterium is most closely related to
      Mycobacterium cosmeticum; however, growth and biochemical features indicate that
      it is distinctly different. Here, we highlight for the first time an unusual NTM
      that is a probable cause of ear infection. 

PMID- 25866686
TI  - Pseudomonas aeruginosa Acquisition in Cystic Fibrosis Patients in Context of
      Otorhinolaryngological Surgery or Dentist Attendance: Case Series and Discussion
      of Preventive Concepts.
AB  - Introduction. P. aeruginosa is the primary cause for pulmonary destruction and
      premature death in cystic fibrosis (CF). Therefore, prevention of airway
      colonization with the pathogen, ubiquitously present in water, is essential.
      Infection of CF patients with P. aeruginosa after dentist treatment was proven
      and dental unit waterlines were identified as source, suggesting prophylactic
      measures. For their almost regular sinonasal involvement, CF patients often
      require otorhinolaryngological (ORL) attendance. Despite some fields around ORL
      procedures with comparable risk for acquisition of P. aeruginosa, such CF cases
      have not yet been reported. We present four CF patients, who primarily acquired
      P. aeruginosa around ORL surgery, and one around dentist treatment. Additionally,
      we discuss risks and preventive strategies for CF patients undergoing ORL
      treatment. Perils include contact to pathogen-carriers in waiting rooms,
      instrumentation, suction, drilling, and flushing fluid, when droplets containing
      pathogens can be nebulized. Postsurgery mucosal damage and debridement impair
      sinonasal mucociliary clearance, facilitating pathogen proliferation and
      infestation. Therefore, sinonasal surgery and dentist treatment of CF patients
      without chronic P. aeruginosa colonization must be linked to repeated
      microbiological assessment. Further studies must elaborate whether all CF
      patients undergoing ORL-surgery require antipseudomonal prophylaxis, including
      nasal lavages containing antibiotics. Altogether, this underestimated risk
      requires structured prevention protocols. 

PMID- 25866688
TI  - Acute aortic occlusion presenting as flaccid paraplegia.
AB  - A 67-year-old male known to be hypertensive and diabetic had a sudden onset of
      severe low back pain and flaccid paraplegia with no sensory level or bladder
      affection and the distal pulsations were felt. Acute compressive myelopathy was
      excluded by MRI of the dorsal and lumbar spines. The nerve conduction study and
      CSF analysis was suggestive of acute demyelinating polyneuropathy. The patient
      developed ischemic changes of the lower limb and CT angiography revealed severe
      stenosis of the abdominal aorta and both common iliac arteries. We emphasize the
      importance of including acute aortic occlusion in the differential diagnosis of
      acute flaccid paraplegia especially in the presence of severe back pain even if
      the distal pulsations were felt. 

PMID- 25866689
TI  - A unique presentation of occult primary breast cancer with a review of the
      literature.
AB  - We are reporting a case of a 34-year-old woman with occult primary breast cancer
      discovered after initially presenting with neurological symptoms. She was
      successfully treated with neoadjuvant chemotherapy followed by definitive
      axillary lymph node dissection and ipsilateral whole breast radiotherapy. The
      case presented is unique due to the rarity of occult primary breast cancer,
      especially in light of her initial confounding neurological signs and symptoms,
      which highlights the importance of careful staging. 

PMID- 25866690
TI  - Safety and Efficacy of Combined Yttrium 90 Resin Radioembolization with
      Aflibercept and FOLFIRI in a Patient with Metastatic Colorectal Cancer.
AB  - Background. When associated with isolated four or fewer liver foci, metastatic
      colorectal cancer is amenable to surgical resection. Alternative therapeutic
      methods for isolated liver metastases include radioembolization with yttrium 90
      (Y90) and transarterial chemoembolization (TACE). We present here a case of a
      patient with two sites of liver metastatic disease from colorectal cancer who
      underwent Y90 radioembolization combined with aflibercept and FOLFIRI. Case
      Report. A 56-year-old female with history of bilateral breast cancer and
      metastatic colon cancer with prior hemicolectomy and 4 previous chemotherapy
      regimens developed liver metastasis. She was started on aflibercept and FOLFIRI
      and concurrently underwent two treatments of radioembolization with Y90,
      initially targeting the largest right lobe tumor, and then a subsequent treatment
      targeting the smaller left lobe tumor with retreatment of the right lobe tumor.
      Her liver metastases exhibited partial response on imaging utilizing the modified
      RECIST criteria. Interestingly, the patient CEA levels decreased after the
      procedure. Discussion. This is the first reported case of a patient managed with
      radioembolization with Y90 combined with aflibercept, an anti-VEGF treatment, and
      FOLFIRI. An ongoing randomized clinical trial aims to define the role of combined
      targeted therapy and chemotherapy with radioembolization with Y90. 

PMID- 25866691
TI  - An office-based procedure for hyphema treatment.
AB  - Three cases of hyphema in three different eyes were treated in the office using
      an anterior chamber fluid-gas exchange technique. Hyphemas were associated with
      complications of underlying systemic and retinal disease and in the postoperative
      period of vitrectomy procedures. Patients were successfully treated without
      requiring return to operating room. 

PMID- 25866692
TI  - Methicillin-Resistant Staphylococcus aureus Ocular Infection after Corneal Cross
      Linking for Keratoconus: Potential Association with Atopic Dermatitis.
AB  - Purpose. To report the risk of methicillin-resistant Staphylococcus aureus (MRSA)
      ocular infection after UVA-riboflavin corneal collagen cross-linking in a patient
      with atopic dermatitis. Methods. A 22-year-old man, with bilateral evolutive
      keratoconus and atopic dermatitis, underwent UVA-riboflavin corneal cross-linking
      and presented with rapidly progressive corneal abscesses and cyclitis in the
      treated eye five days after surgery. The patient was admitted to the hospital and
      treated with broad-spectrum antimicrobic therapy. Results. The patient had
      positive cultures for MRSA, exhibiting a strong resistance to antibiotics.
      Antibiotic therapy was modified and targeted accordingly. The intravitreal
      reaction is extinguished, but severe damage of ocular structures was unavoidable.
      Conclusion. Riboflavin/UVA corneal cross-linking is considered a safe procedure
      and is extremely effective in halting keratoconus' progression. However, this
      procedure is not devoid of infectious complications, due to known risk factors
      and/or poor patients' hygiene compliance in the postoperative period. Atopic
      dermatitis is a common disease among patients with keratoconus and Staphylococcus
      aureus colonization is commonly found in patients with atopic dermatitis.
      Therefore, comorbidity with atopic dermatitis should be thoroughly assessed
      through clinical history before surgery. A clinical evaluation within three days
      after surgery and the imposition of strict personal hygiene rules are strongly
      recommended. 

PMID- 25866693
TI  - Prolonged ileus in an infant presenting with primary congenital hypothyroidism.
AB  - Congenital hypothyroidism (CH) is the most common endocrine disorder affecting
      the newborn. Universal newborn screening (NBS) has virtually eliminated the
      static encephalopathy and devastating neurodevelopmental syndrome known as
      cretinism. This report describes the presentation of an infant referred by the
      primary pediatrician to our hospital at 12 days of age for confirmatory testing
      after the NBS was consistent with CH. The infant had hypoglycemia secondary to
      lethargy and poor feeding and required transfer to the neonatal intensive care
      unit for worsening abdominal distension despite normalization of serum thyroid
      function tests following hormone replacement. In particular, the recalcitrant
      ileus and secondary bowel obstruction resulted in an additional diagnostic workup
      and lengthened hospital day. Our report highlights the acute gastrointestinal
      consequences of hypothyroidism despite evidence of effective treatment. We
      believe that the preclinical detection and immediate therapy for CH have lessened
      the prevalence of this presentation in general practice, and hence practitioners
      are less likely to be familiar with its natural history and management. 

PMID- 25866694
TI  - Kaposi's Sarcoma Presenting as Acute Small Bowel Obstruction Diagnosed on
      Multidetector Computed Tomography with Histopathological Correlation.
AB  - Kaposi's sarcoma was originally described by Moritz Kaposi in 1872 as a rare form
      of multiple hemorrhagic skin lesions. Today it is well documented as a systemic,
      multifocal, steadily progressive reticuloendothelial system tumor with a
      predilection for skin and visceral involvement. It occasionally presents as a
      visceral disease without skin manifestations. We report a case of Kaposi's
      sarcoma of the small bowel in a seropositive patient who presented with acute
      right lower quadrant pain and was diagnosed with intestinal obstruction with
      perforation on contrast-enhanced multidetector computed tomography (MDCT). The
      diagnosis was confirmed as Kaposi's sarcoma on postoperative histopathological
      analysis. 

PMID- 25866695
TI  - Benign multicystic peritoneal mesothelioma: a rare tumour of the abdomen.
AB  - Benign multicystic peritoneal mesothelioma: a rare tumor of the abdomen, is a
      diagnostic dilemma. This report emphasizes the importance of diagnostic
      laparoscopy in the diagnosis of the tumour. 

PMID- 25866696
TI  - Retroperitoneal lymphangioma in an adult: a case report of a rare clinical
      entity.
AB  - Background. Retroperitoneal lymphangioma is a rare, benign mesodermal tumor
      arising from the retroperitoneal lymphatics which usually presents in infancy and
      it is worthy to report a case when it has presented in an adult. After a thorough
      literature search in English we concluded that less than 200 cases of adult
      retroperitoneal lymphangioma have been reported so far. Apart from being a rare
      entity it also presents as a diagnostic dilemma and final diagnosis is often made
      on surgical exploration. Case Presentation. We report a case of retroperitoneal
      lymphangioma in a 55-year-old male who presented with abdominal distension and
      dull aching abdominal pain. Conclusion. Retroperitoneal lymphangiomas are rare
      tumors of infancy but may also present in adults where they are a diagnostic
      challenge. Differentiating cystic lymphangiomas from other cystic growths by
      imaging studies alone are often inconclusive and surgery is frequently required
      for definitive diagnosis and to ameliorate the symptoms. 

PMID- 25866698
TI  - Morphological changes and altered expression of antioxidant proteins in a
      heterozygous dynein mutant; a mouse model of spinal muscular atrophy.
AB  - OBJECTIVE: There is increased evidence that oxidative stress is involved in
      exacerbations of neurodegenerative diseases and spinal muscular atrophies.
      METHODS: We examined changes in morphology and expression of antioxidant proteins
      and peroxiredoxins in motor neurons of lumbar spinal cord, dorsal root ganglion
      sensory neurons, macroglial cells and quadriceps muscles of newborn heterozygous
      Loa/+ mice ("legs at odd angles"), a mouse model for early onset of the spinal
      muscular atrophy with lower extremity predominance (SMA-LED). RESULTS: Our data
      indicate that newborn Loa-mice develop: neuroinflammation of the sensory and
      motor neurons; muscular inflammation with atrophic and denervated myofibers;
      increased expression of neuronal mitochondrial peroxiredoxins (Prxs) 3, 5 and
      cytoplasmic Prx 6 in motor and sensory neurons, myofibers, fibroblasts of
      perimysium and chondrocytes of cartilage; and decreased expression of Prx 6 by
      glial cells and in extracellular space surrounding motor neurons. CONCLUSION: The
      decrease in expression of Prx 6 by glial cells and extracellular Prx 6 secretion
      in early stages of the pathological conditions is consistent with the hypothesis
      that chronic oxidative stress may lead to neurodegeneration of motor neurons and
      exacerbation of the pathology.

PMID- 25866697
TI  - Contemporary Approaches for Identifying Rare Bone Disease Causing Genes.
AB  - Recent improvements in the speed and accuracy of DNA sequencing, together with
      increasingly sophisticated mathematical approaches for annotating gene networks,
      have revolutionized the field of human genetics and made these once time
      consuming approaches assessable to most investigators. In the field of bone
      research, a particularly active area of gene discovery has occurred in patients
      with rare bone disorders such as osteogenesis imperfecta (OI) that are caused by
      mutations in single genes. In this perspective, we highlight some of these
      technological advances and describe how they have been used to identify the
      genetic determinants underlying two previously unexplained cases of OI. The
      widespread availability of advanced methods for DNA sequencing and bioinformatics
      analysis can be expected to greatly facilitate identification of novel gene
      networks that normally function to control bone formation and maintenance.

PMID- 25866699
TI  - A Prototype Head-Motion Monitoring System for In-Home Vestibular Rehabilitation
      Therapy.
AB  - This work reports the use of a head-motion monitoring system to record patient
      head movements while completing in-home exercises for vestibular rehabilitation
      therapy. Based upon a dual-axis gyroscope (yaw and pitch, +/- 500-degrees/sec
      maximum), angular head rotations were measured and stored via an on-board memory
      card. The system enabled the clinician to document exercises at home. Several
      measurements were recorded in one patient with unilateral vestibular
      hypofunction: The total time of exercise for the week (118 minutes) was
      documented and compared with expected weekly exercise time (140 minutes). For
      gaze stabilization exercises, execution time of 60 sec was expected, and observed
      times ranged from 75-100 sec. An absence of rest periods between each exercise
      instead of the recommended one minute rest period was observed. Maximum yaw head
      velocities from approximately 100-350 degrees/sec were detected. A second subject
      provided feedback concerning the ease of use of the HAMMS device. This pilot
      study demonstrates, for the first time, the capability to capture the head-motion
      "signature" of a patient while completing vestibular rehabilitation exercises in
      the home and to extract exercise regime parameters and monitor patient adherence.
      This emerging technology has the potential to greatly improve rehabilitation
      outcomes for individuals completing in-home gaze stabilization exercises.

PMID- 25866702
TI  - Muller cell alignment in bird fovea: possible role in vision.
AB  - Birds which possess high visual acuity, such as eagles and falcons, are known to
      have retinas with a deep conically curved central foveal pit. There have been
      different attempts to explain the importance of this particular shape of the
      fovea in visual resolution. Recently, the function of Muller cells as "light
      fibers" was discovered, showing how the endfeet of Muller cells trap the light
      and then transfer it to a single cone photoreceptor. Here we describe how the
      endfeet of Muller cells line the walls of the foveal pit in the Pied Flycatcher,
      and how the Muller cell body extends its processes towards individual cones,
      forming machinery that could allow for light transfer from the pit wall to the
      photoreceptor layer alongside the pit. We describe how this construction may send
      an image from the fovea to the cones, and also, how the angular positioning of
      Muller cells, being optical extensions of the cones, has the advantage of being
      much denser than on a flat or slightly curved fovea. We, therefore, suggest that
      this type of optic fiber alignment can be used as a novel type of "amplifying
      array" that simply increases the amount of megapixels at the photoreceptor cell
      layer.

PMID- 25866701
TI  - Separation of Lignin from Corn Stover Hydrolysate with Quantitative Recovery of
      Ionic Liquid.
AB  - Abundant lignocellulosic biomass could become a source of sugars and lignin,
      potential feedstocks for the now emergent bio-renewable economy. The production
      and conversion of sugars from biomass have been well-studied, but far less is
      known about the production of lignin that is amenable to valorization. Here we
      report the isolation of lignin generated from the hydrolysis of biomass dissolved
      in the ionic liquid 1-butyl-3-methylimidazolium chloride. We show that lignin can
      be isolated from the hydrolysate slurry by simple filtration or centrifugation,
      and that the ionic liquid can be recovered quantitatively by a straightforward
      wash with water. The isolated lignin is not only free from ionic liquid, but also
      lacks cellulosic residues and is substantially depolymerized, making it a
      promising feedstock for valorization by conversion into fuels and chemicals.

PMID- 25866703
TI  - Global emissions of terpenoid VOCs from terrestrial vegetation in the last
      millennium.
AB  - We investigated the millennial variability (1000 A.D.-2000 A.D.) of global
      biogenic volatile organic compound (BVOC) emissions by using two independent
      numerical models: The Model of Emissions of Gases and Aerosols from Nature
      (MEGAN), for isoprene, monoterpene, and sesquiterpene, and Lund-Potsdam-Jena
      General Ecosystem Simulator (LPJ-GUESS), for isoprene and monoterpenes. We found
      the millennial trends of global isoprene emissions to be mostly affected by land
      cover and atmospheric carbon dioxide changes, whereas monoterpene and
      sesquiterpene emission trends were dominated by temperature change. Isoprene
      emissions declined substantially in regions with large and rapid land cover
      change. In addition, isoprene emission sensitivity to drought proved to have
      significant short-term global effects. By the end of the past millennium MEGAN
      isoprene emissions were 634 TgC yr-1 (13% and 19% less than during 1750-1850 and
      1000-1200, respectively), and LPJ-GUESS emissions were 323 TgC yr-1(15% and 20%
      less than during 1750-1850 and 1000-1200, respectively). Monoterpene emissions
      were 89 TgC yr-1(10% and 6% higher than during 1750-1850 and 1000-1200,
      respectively) in MEGAN, and 24 TgC yr-1 (2% higher and 5% less than during 1750
      1850 and 1000-1200, respectively) in LPJ-GUESS. MEGAN sesquiterpene emissions
      were 36 TgC yr-1(10% and 4% higher than during 1750-1850 and 1000-1200,
      respectively). Although both models capture similar emission trends, the
      magnitude of the emissions are different. This highlights the importance of
      building better constraints on VOC emissions from terrestrial vegetation.

PMID- 25866704
TI  - Identification, estimation and approximation of risk under interventions that
      depend on the natural value of treatment using observational data.

PMID- 25866700
TI  - Mobile DNA in the pathogenic Neisseria.
AB  - The genus Neisseria contains two pathogenic species of notable public health
      concern: Neisseria gonorrhoeae and Neisseria meningitidis. These pathogens
      display a notable ability to undergo frequent programmed recombination events.
      The recombination mediated pathways of transformation and pilin antigenic
      variation in the Neisseria are well studied systems that are critical for
      pathogenesis. Here we will detail the conserved and unique aspects of
      transformation and antigenic variation in the Neisseria. Transformation will be
      followed from initial DNA binding through recombination into the genome with
      consideration to the factors necessary at each step. Additional focus is paid to
      the unique type IV secretion system that mediates donation of transforming DNA in
      the pathogenic Neisseria. The pilin antigenic variation system uses programed
      recombinations to alter a major surface determinant which allows immune avoidance
      and promotes infection. We discuss the trans- and cis- acting factors which
      facilitate pilin antigenic variation and present the current understanding of the
      mechanisms involved in the process.

PMID- 25866705
TI  - Simbody: multibody dynamics for biomedical research.
AB  - Multibody software designed for mechanical engineering has been successfully
      employed in biomedical research for many years. For real time operation some
      biomedical researchers have also adapted game physics engines. However, these
      tools were built for other purposes and do not fully address the needs of
      biomedical researchers using them to analyze the dynamics of biological
      structures and make clinically meaningful recommendations. We are addressing this
      problem through the development of an open source, extensible, high performance
      toolkit including a multibody mechanics library aimed at the needs of biomedical
      researchers. The resulting code, Simbody, supports research in a variety of
      fields including neuromuscular, prosthetic, and biomolecular simulation, and
      related research such as biologically-inspired design and control of humanoid
      robots and avatars. Simbody is the dynamics engine behind OpenSim, a widely used
      biomechanics simulation application. This article reviews issues that arise
      uniquely in biomedical research, and reports on the architecture, theory, and
      computational methods Simbody uses to address them. By addressing these needs
      explicitly Simbody provides a better match to the needs of researchers than can
      be obtained by adaptation of mechanical engineering or gaming codes. Simbody is a
      community resource, free for any purpose. We encourage wide adoption and invite
      contributions to the code base at https://simtk.org/home/simbody.

PMID- 25866706
TI  - Sentinel lymph node mapping of a breast cancer of the vulva: Case report and
      literature review.
AB  - Ectopic breast tissue is rare and typically presents as an axillary mass.
      Previous reports have identified ectopic breast tissue in the vulva, but
      malignancy is exceedingly uncommon. We present a 62 years old with locally
      advanced breast carcinoma arising in the vulva demonstrates the utilization of
      sentinel lymph node mapping to identify metastatic lymph nodes previously unable
      to be identified via traditional surgical exploration. Our case supports the
      principles of adjuvant therapy for breast cancer to be applied to ectopic breast
      cancer arising in the vulva. A literature review highlights common key points in
      similar cases to guide management. 

PMID- 25866708
TI  - Hemodynamic changes following endotracheal intubation in patients undergoing
      cesarean section with general anesthesia: application of glidescope(r)
      videolaryngoscope versus direct laryngoscope.
AB  - BACKGROUND: Endotracheal intubation is usually associated with hemodynamic
      changes, especially in patients undergoing cesarean section by general
      anesthesia. GlideScope(r) videolaryngoscope (GVL) is a novel video laryngoscope,
      which does not need direct exposure of vocal cords and produces lesser
      hemodynamic changes due to lower degrees of trauma and stimuli to oropharynx than
      the Macintosh direct laryngoscope (MDL). OBJECTIVES: The aim of this study was to
      compare hemodynamic changes following endotracheal intubation with GVL and MDL in
      patients undergoing cesarean section by general anesthesia. MATERIALS AND
      METHODS: Seventy patients undergoing elective cesarean section by general
      anesthesia requiring endotracheal intubation were randomly allocated to be
      intubated with either GVL (n = 35) or MDL (n = 35). Systolic, diastolic and mean
      arterial blood pressure (MAP), as well as pulse rates, and rate pressure product
      (RPP) were compared at baseline, after induction of anesthesia, and after
      intubation at one-minute interval for five minutes between the two groups. The
      patients were also compared for Mallampati score, sore throat, intubation time
      and neonates' Apgar scores. RESULTS: The patients were similar regarding
      systolic, diastolic and mean arterial blood pressure. Pulse rate changes were
      significantly lower only at 1 and 3 minutes in the GVL group. The intubation
      times were 9.3 +/- 1.4 and 10.6 +/- 1.7 seconds in the MDL and GVL groups,
      respectively (P > 0.05). RPP was also lower in the GVL group at 1 and 2 minutes
      (P < 0.05) and returned to baseline afterwards. There was no significant
      difference between the groups for Mallampati score, sore throat and Apgar scores.
      CONCLUSIONS: Our study revealed that hemodynamic parameters with GVL are only
      better preserved in the first three minutes after intubation in patients
      undergoing elective cesarean section and patients are similar regarding
      intubation time, sore throat and Apgar score.

PMID- 25866707
TI  - Significance of Mouse Models in Dissecting the Mechanism of Human Eosinophilic
      Gastrointestinal Diseases (EGID).
AB  - Evidence suggests that eosinophils play a significant role in promoting several
      gastrointestinal diseases, and animal models are the significant tools to
      understand the pathogenesis of eosinophil-associatd inflammatory disorders. The
      focus of this review is on the significance of mouse models that mimic the
      characteristics of human eosinophilic gastrointestinal diseases. Eosinophils are
      the important leukocytes with diverse functions in the gastrointestinal tract,
      such as excretion of intestinal parasites and promoting the pathogenesis of a
      numerous allergic gastrointestinal disorders like food allergy, parasitic
      infection, allergic gastroenteritis, allergic colitis, and eosinophilic
      esophagitis. Among these gastrointestinal diseases, the eosinophilic esophagitis
      is the most recently recognized disease and the mouse models are proven to be an
      effective tool to understand the pathophysiology of disease and to test novel
      treatment strategies. Based on patients allergic conditions and the gene
      overexpressed in human EGID, a number of gene overexpressed and allergen
      challenged mouse models of gastrointestinal disorders were developed. These
      models were utilized to explore the mechanism(s) that promotes the eosinophil
      mediated gastrointestinal diseases including the role of the eosinophil
      responsive cytokines and chemokines. Herein, we have provided a detailed
      overviews of the mouse models of gastrointestinal disorders that mimic the human
      eosinophilic gastrointestinal diseases and can be utilized as a tool for
      understanding the diseases pathogenesis and developing novel therapeutic targets.

PMID- 25866709
TI  - Success rate of airway devices insertion: laryngeal mask airway versus
      supraglottic gel device.
AB  - BACKGROUND: The main important method for airway management during anesthesia is
      endotracheal intubation. Laryngeal mask airway (LMA) and supraglottic gel device
      (I-Gel) are considered alternatives to endotracheal tube. OBJECTIVES: This study
      sought to assess the success rate of airway management using LMA and I-Gel in
      elective orthopedic surgery. PATIENTS AND METHODS: This single-blinded randomized
      clinical trial was performed on 61 ASA Class 1 and 2 patients requiring minor
      orthopedic surgeries. Patients were randomly allocated to two groups of LMA and I
      Gel. Supraglottic airway placement was categorized into three groups regarding
      the number of placement attempts, i.e. on the first, second, and third attempts.
      Unsuccessful placement on the third attempt was considered failure and
      endotracheal tube was used in such cases. The success rate, insertion time, and
      postoperative complications such as bleeding, sore throat, and hoarseness were
      recorded. RESULTS: In the I-Gel group, the success rate was 66.7% for placement
      on the first attempt, 16.7% for the second, and 3.33% for the third attempt. In
      the LMA group, the success rates were 80.6% and 12.9% for the first and second
      attempts, respectively. Failure in placement occurred in four cases in the I-Gel
      and two cases in LMA groups. The mean insertion time was not significantly
      different between two groups (21.35 seconds in LMA versus 27.96 seconds in I-Gel,
      P = 0.2). The incidence of postoperative complications was not significantly
      different between study groups. CONCLUSIONS: I-Gel can be inserted as fast as LMA
      with adequate ventilation in patients and has no major airway complications.
      Therefore, it could be a good alternative to LMA in emergency airway management
      or general anesthesia.

PMID- 25866710
TI  - Comparison of the effects of heparin and 0.9% sodium chloride solutions in
      maintenance of patency of central venous catheters.
AB  - BACKGROUND: Occlusion of central venous catheters is one of the limiting factors
      in using them. Heparinized saline solution is the standard solution used for
      keeping the catheters open. OBJECTIVES: This study aimed to determine the effect
      of heparin saline solution and normal saline in maintenance of patency of central
      venous catheters. PATIENTS AND METHODS: This double-blind study was performed on
      84 patients of intensive care unit who had central venous catheters. The patients
      were randomly divided into two groups of heparin saline receivers and normal
      saline receivers. In the heparin group after each drug injection into the lumen,
      3 mL of heparin saline solution was injected in the catheter as well. The other
      group only received 10 mL of normal saline instead. The catheters were examined
      for blood return and flushing every eight hours for 21 days. Data was analyzed
      using SPSS software version 20 and descriptive and analytic statistics were
      studied. RESULTS: There was no significant difference in the rate of flushing (P
      = 0.872) and possibility of taking blood samples from catheters (P = 0.745) in
      the two groups of heparin and normal saline receivers. Furthermore, using heparin
      had no effect on prolonging the survival of catheters. CONCLUSIONS: Considering
      possible side effects of heparin and the increase in treatment charges and the
      fact that using heparin did not have a significant effect on patency and survival
      of catheters in the studied patients, it is recommended to use normal saline
      solution to maintain the patency of central venous catheters.

PMID- 25866711
TI  - Neuraxial dexmedetomidine: wonder drug or simply harmful.

PMID- 25866712
TI  - Optimization of the Expression of Reteplase in Escherichia coli TOP10 Using
      Arabinose Promoter.
AB  - BACKGROUND: Reteplase is a mutant version of t-PA (tissue plasminogen activator)
      with prolonged half-life. In the present study, E. coli Top 10 bacteria were
      utilized in the production of reteplase, which is the nonglycosylated active
      domain of t-PA. Reteplase gene was ligated into pBAD/gIII plasmid which, allows
      secretion of this protein in periplasmic space. It would allow the correct
      formation of disulfide bonds in protein structure. OBJECTIVES: This study aimed
      at expression of reteplase in optimum condition. In this study, the reteplase
      gene was cloned and expressed in Escherichia coli top 10 as a suitable host cell
      and its expression was optimized. MATERIALS AND METHODS: The recombinant plasmid,
      pET15b/reteplase was digested by NcoI and BamHI restriction enzymes; while
      pBAD/gIIIA vector was digested by NcoI and BglII. Then the insert and vector were
      ligated and used for transformation of E. coli Top10 cells by heat shock method.
      Overnight culture of transformed bacteria was induced by L-arabinose in various
      concentrations (0.2, 0.02, 0.002, and 0.0002%) and at various temperatures.
      RESULTS: The obtained recombinant plasmid was sequenced to confirm the presence
      and correct framing of reteplase gene regarding the expression of reteplase.
      Maximum production of this enzyme was obtained under the following condition:
      0.0002% L-arabinose at 37 degrees C for 2 hours incubation. The purified protein
      was detected on SDS-PAGE (sodium dodecyl sulfate Polyacrylamide gel
      electrophoresis) as a 66 kDa band. The concentration of t-PA standard was 1 unit
      which is equal to 12 ug/mL. The enzymatic activity of samples was measured as 0.8
      units compared to the standards. CONCLUSIONS: Reteplase was expressed in E. coli
      Top 10 after activation of pBAD/gIIIA promoter region by arabinose and optimized.

PMID- 25866713
TI  - Long-term methadone intake and genotoxicity in addicted patients.
AB  - BACKGROUND: It is well known that contact with some physical, chemical or
      biological compounds can increase the incidence of mutation. Among these
      compounds, are pharmaceuticals that meet long duration of use and potentially
      could be misused and taken more than the ordered dosage. OBJECTIVES: The aim of
      this study was to evaluate mutagenic effect of methadone in addicted patients
      referred to Imam Khomeini Hospital in Ahvaz by single cell gel electrophoresis
      technic or comet assay. PATIENTS AND METHODS: In this study, 90 subjects were
      divided into dichromate treated group, no treated healthy volunteers group and
      test group. Each group included 30 subjects. Screening was performed according to
      questionnaire and qualified subjects were entered the study. Blood samples were
      collected and lymphocytes were isolated, mixed with low melting point agarose for
      slide preparation according to standard method. Slides were analyzed using
      fluorescence microscope and comet patterns were assessed. RESULTS: The
      mutagenicity index in addicted group was robustly higher than healthy volunteers.
      Fortunately, this significant difference was lower than positive control.
      CONCLUSIONS: Genome instability in addicted patients was demonstrated in this
      study. Controversially, considering incoherent results of previous studies and
      our data, more studies in longer duration of methadone use are needed to
      elucidate the consequence.

PMID- 25866714
TI  - Hydroalcoholic Extract of Ferulago angulata Improves Memory and Pain in Brain
      Hypoperfusion Ischemia in Rats.
AB  - BACKGROUND: Cerebral ischemia causes some disorders in behavioral patterns,
      including memory disorders and pain, which is due to the production of free
      radicals. Ferulago angulata, known in Iran as chavir, contains some bioactive
      compounds having antioxidant and free radical-scavenging properties. OBJECTIVES:
      This study aimed to evaluate the effect of two weeks oral administration of
      hydroalcoholic extract of F. angulate (100, 200 and 400 mg/kg) on pain as well as
      active and passive avoidance memories after permanent, bilateral common carotid
      artery occlusion or cerebral ischemia/hypoperfusion in male adult rats. MATERIALS
      AND METHODS: In this study, 35 male rats were randomly allocated to test and
      control groups. To make animal model of permanent cerebral
      hypoperfusion/ischemia, carotid arteries were ligatured as upper and lower and
      cut bilaterally. RESULTS: It was found that the administration of 400 mg/kg
      hydroalcoholic extract of F. angulate for two weeks after brain hypoperfusion
      ischemia increased the passive avoidance memory (P < 0.001) and latency time of
      painful tail reflex significantly (P < 0.05). CONCLUSIONS: Ferulago angulata
      extract, because of its antioxidant activities, is probably capable of removing
      free radicals and oxidant substances from brain and thus it can improve
      behavioral disorders in brain hypoperfusion ischemia model.

PMID- 25866715
TI  - Anti-inflammatory effect of simvastatin in hemodialysis patients.
AB  - BACKGROUND: Patients in the final stages of renal failure have accelerated
      inflammation conditions. Inflammation causes progressive kidney damage, faster
      progression of atherogenesis, chronic malnutrition and increased anemia,
      resulting in lower life expectancy of patients under dialysis. Statins have
      pleiotropic effects, because the drug has effects more than just decreasing
      lipids such as antioxidant effects, changes in endothelial dysfunction,
      stabilizing the plaque and immune system regulator. OBJECTIVES: The aim of the
      study was to evaluate anti-inflammatory effect of simvastatin (one of the
      statins) in patients under hemodialysis. PATIENTS AND METHODS: In this clinical
      trial study, 40 patients under hemodialysis were studied for 12 weeks. Patients
      were divided into treatment (25 cases) and control groups (15 cases). The
      treatment group received a daily dosage of 20 mg of simvastatin, while the
      control group received no medication. The serum amounts of hs-CRP, IL6, Hb and
      WBC count were measured and compared at baseline and after 12 weeks. In addition,
      probable hepatic and muscular complications were studied in patients. RESULTS: At
      baseline, each of treatment and control groups had similar characteristics.
      During the study, the average level of CRP decreased in the treatment group (P =
      0.04), while it was increased in the control group. The amount of serum IL-6
      dropped in the treatment group (P = 0.01); however, it was increased in the
      control group. In both groups, the level of Hb increased significantly at the end
      of study in the treatment group (P = 0.007) and the control group (P = 0.016).
      The average WBC count decreased significantly in the treatment group and the
      control group (P = 0.003). There was no significant change in hepatic and
      muscular enzymes in the two groups. CONCLUSIONS: End stage renal disease (ESRD)
      have accelerated inflammatory conditions. Simvastatin clearly lowers the serum
      levels of CRP and IL-6, and the white blood cell count in dialysis patients.
      Administering Simvastatin to dialysis patients is safe.

PMID- 25866716
TI  - Evaluation of Hymenodictyon excelsum Phytochemical's Therapeutic Value Against
      Prostate Cancer by Molecular Docking Study.
AB  - BACKGROUND: Hymenodictyon excelsum is a medicinal plant traditionally used for
      tumor treatment as it contains phytochemicals of anthraquinone and coumarin
      class. OBJECTIVES: The aim of the present study was to unfold the therapeutic
      value of selected phytocompounds of Hymenodictyon excelsum in prostate cancer.
      MATERIALS AND METHODS: Eight phytochemicals were selected based on the literature
      search including anthragallol, damnacanthal, esculin, lucidin, morindone,
      nordamnacanthal, rubiadin, and soranjidiol while dihydrotestosterone was
      considered as the control. Human androgen receptor (AR) ligand binding domain
      (PDB id: 1e3g) was selected as the receptor for subsequent computational docking
      study. First, the selected phytocompounds were screened for their drug likeness
      and safety profile. Molegro Virtual Docker (MVD) was subjected only to drug-like
      and safe phytocompounds for the computational docking study. RESULTS: Except for
      anthragallol, nordamnacanthal and rubiadin, all the ligands were drug-like and
      safe. Results of the docking study suggest a favorable binding of esculin to the
      receptor with respect to dihydrotestosterone. Analysis of docking pattern
      revealed a nearly similar ligand-receptor interaction for both
      dihydrotestosterone and esculin. CONCLUSIONS: The anthraquinone and coumarin
      principles of H. excelsum have an anti-prostate cancer effect that has been
      proposed to be exerted by antagonistic effects on AR.

PMID- 25866717
TI  - The Effect of Hydro-Alcoholic Extract of Foeniculum vulgare Mill on Leukocytes
      and Hematological Tests in Male Rats.
AB  - BACKGROUND: Medicinal plants have a long history in treating blood disorders,
      which is one of the most common problems in today's advanced world. Fennel
      (Foeniculum vulgare) is a medicinal plant with a high content of polyphenols and
      has antioxidant and immunomodulatory properties. OBJECTIVES: The aim of this
      study was to evaluate the effect of hydro-alcoholic extract of fennel on some
      hematological indices in male rats. MATERIALS AND METHODS: In this experimental
      study, thirty male Wistar rats were divided into six groups (five rats in each
      group). The first group (control) did not receive any dose; the second group
      (sham) received 1 mL normal saline (extraction solvent); and the experimental
      groups 1, 2, 3 and 4 respectively received 1 mL hydro alcoholic extract of fennel
      in four doses of 250, 500, 750 and 1000 mg/kg of body weight every 48 hours for
      30 days by gavage. One day after the last gavage following induction of
      anesthesia and taking blood from the heart of rats, measurement of red and white
      blood cells, hemoglobin, hematocrit and tests of bleeding and coagulation time
      (CT) were performed. The data was analyzed by one-way ANOVA test using SPSS15
      software. RESULTS: Fennel increased mean RBC (7.54 +/- 0.53 * 106) and WBC (5.89
      +/- 0.78 * 103) values, especially at a dose of 250 mg/mL and CT (2.45 +/- 0.20)
      at a dose of 500mg/mL compared to the control group (P < 0.05). CONCLUSIONS:
      Fennel increased red and white blood cells probably due to the presence of
      polyphenols and antioxidant activity of fennel and reduced negative effects of
      free radicals on blood cells.

PMID- 25866718
TI  - Ginger from ancient times to the new outlook.
AB  - CONTEXT: Ginger is the rhizome of Zingiber officinale, a perennial plant, used
      alone or in compounds as a spice or remedy in ancient recipes of Iranian
      traditional medicine (ITM) as an effective tonic for the memory and digestive
      system, the opener of hepatic obstructions, aphrodisiac, for expelling compact
      wind from stomach and intestines, diluting, desiccating and emollient of
      phlegmatic and compact humor sticking to body organs, stomach, intestine, brain
      and throat. The ITM scholars believed that ginger was a vermifuge as well as a
      remedy for paralysis and obstructive jaundice. They also revealed that this
      phytomedicine cures diarrhea due to corrupted food. This study aimed to compare
      the medicinal properties (afaal) of ginger in ITM with those indicated in modern
      research. RESULTS: Results of this study showed that the modern phytotherapy
      confirmed some of the properties of ginger. In addition, some of the properties
      of this phytomedicine have not been studied yet. CONCLUSIONS: By studding the ITM
      literature, herb elements or in other words ITM keywords, researchers can predict
      and state some unknown or less known potential pharmacologic effects of medicinal
      plants.

PMID- 25866719
TI  - Enhancement of human skin fibroblasts proliferation as a result of treating with
      quince seed mucilage.
AB  - BACKGROUND: Quince seed mucilage (QSM) has been used in Iranian folk medicine in
      the treatment of wounds and burns. Experimental and clinical studies showed its
      wound healing activity. However, the mechanism by which this agent affects cells
      involved in the wound healing process is unknown. OBJECTIVES: In this study, we
      investigated the effects of QSM at concentrations of 50, 100, 200, and 400 ug/mL
      on human skin fibroblast proliferation as an aspect of promotion of wound
      healing. MATERIALS AND METHODS: Human skin fibroblast cell line (HNFF-P18) was
      used in the experiment. Cell proliferation assay was measured by a MTT assay.
      RESULTS: Cells treated with QSM at concentrations less than 400 ug/mL increased
      their proliferative activity. The concentration of 50 ug/mL was the most
      effective dose after 72 hours treatment. CONCLUSIONS: QSM has the ability to
      stimulate proliferation of human skin fibroblast. This effect suggests that this
      compound can act as a wound healing agent.

PMID- 25866720
TI  - Electro-oxidation mechanism and direct square-wave voltammetric determination of
      lidocaine with a carbon-paste electrode.
AB  - BACKGROUND: Lidocaine hydrochloride (LH) is one of the most extensively used
      local anesthetics and peripheral analgesics. Availability of a simple and
      sensitive assay method for this analyte in pharmaceutical preparations as well as
      development of new voltammetric detectors that can be applied in chromatographic
      systems for determination of this analyte in biological samples are of great
      importance. OBJECTIVES: In this study, a square-wave voltammetric (SWV)
      determination of LH at a bare carbon-paste electrode (CPE) was reported.
      Moreover, the oxidation mechanism for LH molecule at this electrode was
      investigated. MATERIALS AND METHODS: The SW voltammogram of LH solution at CPE
      showed a well-defined peak between +0.80 and +0.88 V depending on a scan rate in
      potassium nitrate (KNO3) solution. Different chemical and instrumental parameters
      influencing the voltammetric response, such as the pH level and scan rate were
      optimized for LH determination. RESULTS: A linear range of 8.0 - 1000.0 MUmol L(
      1) (r(2) = 0.999) was obtained. The limit of detection (LOD) was 0.29 MUmol L(
      1). The relative standard deviations of 2.1% obtained for 0.8 800 MUmol L(-1)
      solution of LH indicated a reasonable reproducibility of the method. CONCLUSIONS:
      The results of this study show that LH in different pharmaceutical preparations
      could be determined with good reliability. In addition, the results reveal that
      the equal numbers of electrons and protons are involved in the oxidation of LH
      and the irreversible oxidation of an analyte was performed via amine groups of LH
      molecule.

PMID- 25866721
TI  - Comparing the effect of visceral fat and barley seed ash (hordeum vulgare L) with
      silversulfadiazine on burn wound healing in rats.
AB  - BACKGROUND: Skin burn is one of the most common complications and remains a major
      public health issue worldwide. OBJECTIVES: This experiment was conducted to study
      the effects of traditional medicine (Visceral Fat and Barely Seed Ash) compared
      with silversulfadiazine (SSD) cream on healing burn wounds in rats. MATERIALS AND
      METHODS: Sixty adult male Wistar rats were randomly divided into four groups of
      equal numbers; each group consisted of 15 animals. After sedation, type II of
      skin burn with 1.5 cm diameter circle was created on the back of rats with a
      heated metal in boiling water. Group one was not treated and considered as
      control. The burned areas in the second, third and fourth groups were applied
      twice a day with normal saline, SSD cream and traditional preparation,
      respectively. Percentage of the burn wound concentration and histopathological
      examinations were used as parameters of our study on days 4, 9and 14. Obtained
      data were compared between the groups and days. RESULTS: SSD cream and
      traditional preparation had better effects on burnt wound healing compared with
      control group. Furthermore, on the final day of study, the average percentage of
      wound concentration in traditional medicine group was significantly greater than
      other groups (P < 0.05). This finding was supported and confirmed by histological
      examination as well. CONCLUSIONS: Traditional preparation significantly decreased
      inflammation and accelerated wound healing in treated rats. Furthermore, the
      findings of this study can be applied clinically in the future.

PMID- 25866722
TI  - Soybean: a potential antipsoriasis agent.

PMID- 25866723
TI  - Evaluation of Sub-acute Oral Toxicity of Lithium Carbonate Microemulsion (Nano
      Size) on Liver and Kidney of Mice.
AB  - BACKGROUND: The development of drug delivery systems has improved the therapeutic
      and toxic properties of existing drugs in therapy. Microemulsion systems are
      novel vehicles for drug delivery, which have been developed in recent years.
      These systems are currently of interest to the pharmaceutical scientist because
      of their considerable potential to act as drug delivery vehicles by incorporating
      into a wide range of drug molecules. Although these systems improved solubility
      and bioavailability of drugs, they may have potential toxic effects on the body
      organs. OBJECTIVES: The purpose of this study was to examine a possible
      hepatotoxic and nephrotoxic effect of lithium carbonate microemulsion (LCME) in a
      mice model. MATERIALS AND METHODS: Eighty male Swiss albino mice were randomly
      allocated to eight experimental groups, as follows: Group 1, as negative control
      group were treated orally with normal saline (0.9% NaCl); Group 2, received
      microemulsion base without drug as control group; Groups 3 to 5, received lithium
      carbonate (LC) solution in doses of 50, 100, and 200 mg/kg, respectively; Groups
      6 to 8, received LCME orally in doses of 50, 100, and 200 mg/kg, respectively.
      All drugs were administered orally for ten consecutive days. Serum glutamate
      pyruvate aminotransferase (SGPT), serum glutamate oxaloacetate aminotransferase
      (SGOT), alkaline phosphatase (ALP), blood urea nitrogen (BUN), and plasma
      creatinine (Cr), as markers of liver and kidney toxicity in treated mice, were
      measured. Furthermore, the changes of tissue were assessed by histopathologic
      examination. RESULTS: The findings showed that serum activity of ALP, SGOT, and
      SGPT and the levels of BUN and Cr in microemulsion base group was greater than
      normal saline group. However, this difference was not significant. Administration
      of LC and LCME in all doses resulted in a significant increase in the levels of
      BUN and serum activity of SGOT and SGPT in comparison to normal saline group (P <
      0.05). Histopathological changes were observed in mice treated with LC or LCME.
      CONCLUSIONS: This study showed that subacute oral administration of different
      doses of LCME with severe toxicity in comparison to the same dose of LC.

PMID- 25866724
TI  - Effect of royal jelly on formalin induced-inflammation in rat hind paw.
AB  - BACKGROUND: Royal Jelly (RJ), a food item secreted by worker honeybees, is a
      mixture that contains protein, glucose, lipid, vitamins, and minerals; it is
      widely used as a commercial medical product. Previous studies have shown that RJ
      has a number of physiological effects, such as anti-inflammatory, antitumor,
      antiallergic and antioxidant activities. OBJECTIVES: In the present study, the
      anti-inflammatory properties of RJ were investigated in formalin-induced rat paw
      edema. MATERIALS AND METHODS: In this study, 30 male Wistar albino rats were
      divided into five equal groups (n = 6) as follows: test groups received different
      doses (25, 50 and 100 mg/kg, ip) of RJ and a negative control group received
      normal saline (5 mL/kg) and a positive control group received aspirin (300 mg/kg,
      i.p). Edema was induced on the right hind paw of the rat by a subplantar
      injection of 100 uL of formalin (2.5%) after 30 minutes. Paw edema was measured
      in the rats received the drugs, saline and aspirin before and after the formalin
      injection during 5 hours, using a plethysmometer. RESULTS: The results showed
      that RJ has a dose-dependent anti-inflammatory effect and the highest anti
      inflammatory effect was observed in the doses of 50 and 100 mg/kg. CONCLUSIONS:
      Royal jelly has potent anti-inflammatory effects compared to aspirin and it could
      be used in the treatment of inflammation. However, further studies are required
      to determine the active components in RJ responsible for this effect and its
      mechanism of action.

PMID- 25866725
TI  - Inhibitory Effects of Physalis alkekengi L., Alcea rosea L., Bunium persicum B.
      Fedtsch. and Marrubium vulgare L. on Mushroom Tyrosinase.
AB  - BACKGROUND: The key enzyme in the process of melanin biosynthesis is tyrosinase.
      Skin hyperpigmentation and browning of foods are undesirable phenomena which
      tyrosinase represents. Therefore, tyrosinase inhibitors have been used
      increasingly for medicinal and cosmetic products. OBJECTIVES: In this study,
      inhibitory effects of four plants including: physalis alkekengi L., Alcea rosea
      L., Bunium persicum B. Fedtsch. and Marrubium vulgare L. on diphenolase activity
      of mushroom tyrosinase were evaluated. MATERIALS AND METHODS: The inhibitory
      activities of hydroalcoholic extracts of plants against oxidation of L-Dopa (as a
      substrate) by mushroom tyrosinase were investigated. RESULTS: The hydroalcoholic
      extract of P. alkekengi showed the most tyrosinase inhibitory effect with IC50 of
      0.09 mg/mL vs. 0.38, 0.38 and 2.82 mg/mL of B. persicum, A. rosea and M. vulgare,
      respectively. M. vulgare exhibited uncompetitive inhibition and other plants
      showed mixed type inhibition on mushroom tyrosinase. CONCLUSIONS: All plants
      could inhibit mushroom tyrosinase, but more investigations on human tyrosinase
      and clinical studies are needed.

PMID- 25866726
TI  - Fungal contaminations of herbal face mask preparations.

PMID- 25866727
TI  - How to Improve Eating Behaviour during Early Childhood.
AB  - Eating behaviour disorder during early childhood is a common pediatric problem.
      Many terminologies have been used interchangeably to describe this condition,
      hindering implementation of therapy and confusing a common problem. The
      definition suggests an eating behaviour which has consequences for family harmony
      and growth. The recent Diagnostic and Statistical Manual of Mental Disorders,
      Fifth Edition does not cover the entire spectrum seen by pediatricians.
      Publications are substantive but level of evidence is most of the time low. This
      purpose of this review is to clarify terminology of eating behaviour problems
      during early childhood; including benign picky eating, limited diets, sensory
      food aversion, selective eating, food avoidance emotional disorder, pervasive
      refusal syndrome, tactile defensiveness, functional dysphagia, neophobia and
      toddler anorexia. This tool is proposed only to ease the clinical management for
      child care providers. Diagnostic criteria are set and management tools are
      suggested. The role of dietary counselling and, where necessary, behavioural
      therapy is clarified. It is hoped that the condition will make its way into
      mainstream pediatrics to allow these children, and their families, to receive the
      help they deserve. 

PMID- 25866728
TI  - Changing Prevalence of Helicobacter pylori Infections in Korean Children with
      Recurrent Abdominal Pain.
AB  - PURPOSE: The aim of this study is to investigate the changing prevalence rate of
      Helicobacter pylori infection in children, of different age groups, with
      recurrent abdominal pain over a 10-year period. METHODS: Children with recurrent
      abdominal pain who visited the pediatric outpatient clinic at university hospital
      were screened for H. pylori. Children were divided into 3 age categories of 4-5,
      6-11, and 12-16 years. To study the changes in the annual prevalence rates of H.
      pylori infection, the study period was divided into 3 time periods: 2004-2007,
      2008-2010, and 2011-2014. Urea breath test was performed for all children aged 4
      16 years, with a cut-off value of 4.00/00 for children aged >=6 years and 70/00
      for children aged <6 years. RESULTS: A total of 2,530 children (1,191 boys) with
      a mean age of 10.0+/-3.0 years (range, 4.0-16.9 years) were included in the
      study. The total prevalence of H. pylori infection was 7.4% (187/2,530). The
      prevalence rate of H. pylori infection in children with recurrent abdominal pain
      was 8.0% (70/873) in 2004-2007, 7.7% (51/666) in 2008-2010, and 6.7% (66/991) in
      the 2011-2014. Nevertheless, a significant difference was observed in the
      prevalence rate between children <12 years old and >=12 years of age (p=0.018).
      CONCLUSION: The prevalence of H. pylori infection in Korean children with
      recurrent abdominal pain was 7.4%, showing no significant decrease in the last 11
      years; however, the prevalence rate in children <12 years old was significantly
      lower than that in those >=12 years old.

PMID- 25866729
TI  - The Efficacy of Saccharomyces boulardii CNCM I-745 in Addition to Standard
      Helicobacter pylori Eradication Treatment in Children.
AB  - PURPOSE: This study aims to investigate Saccharomyces boulardii CNCM I-745 during
      Helicobacter pylori eradication in children. METHODS: One hundred ninety-four H.
      pylori positive children were randomized in two groups. Therapy
      (omeprazole+clarithromycin+amoxicillin or omeprazole+clarithromycin+metronidazole
      in case of penicillin allergy) was given to both groups during two weeks. In the
      treatment group (n: 102) S. boulardii was added to the triple therapy, while the
      control group (n: 92) only received triple therapy. The incidence, onset,
      duration and severity of diarrhea and compliance to the eradication treatment
      were compared. A (13)C urea breath test was done 4 weeks after the end of
      eradication therapy in two groups of 21 patients aged 12 years and older to test
      the H. pylori eradication rate. RESULTS: In the treatment group, diarrhea
      occurred in 12 cases (11.76%), starting after 6.25+/-1.24 days, lasting 3.17+/
      1.08 days, and compliance to eradication treatment was 100%. In the control
      group, diarrhea occurred in 26 cases (28.26%), starting after 4.05+/-1.11 days,
      lasting 4.02+/-0.87 days, and in six cases eradication treatment was stopped
      prematurely (p<0.05). The (13)C urea breath test showed successful H. pylori
      eradication in 71.4% of the patients in the treatment and in 61.9 % in the
      control group (not significant). CONCLUSION: S. boulardii has a beneficial effect
      on the prevention and treatment of diarrhea during H. pylori eradication in
      children. Although S. boulardii did only slightly increase H. pylori eradication
      rate, compliance to eradication treatment was improved.

PMID- 25866730
TI  - Clinical Characteristics of Celiac Disease and Dietary Adherence to Gluten-Free
      Diet among Saudi Children.
AB  - PURPOSE: To describe the clinical characteristics of celiac disease (CD) among
      Saudi children and to determine the adherence rate to gluten free diet (GFD) and
      its determinant factors among them. METHODS: A cross-sectional study was
      conducted, in which all the families registered in the Saudi Celiac Patients
      Support Group were sent an online survey. Only families with children 18 years of
      age and younger with biopsy-confirmed CD were included. RESULTS: The median age
      of the 113 included children was 9.9 years, the median age at symptom onset was
      5.5 years and the median age at diagnosis was 7 years, the median time between
      the presentation and the final diagnosis was 1 year. Sixty two of the involved
      children were females. Ninety two percent of the patients were symptomatic at the
      diagnosis while eight percent were asymptomatic. The commonest presenting
      symptoms included: chronic abdominal pain (59.3%), poor weight gain (54%),
      abdominal distention, gases, bloating (46.1%) and chronic diarrhea (41.6%). Sixty
      percent of the involved children were reported to be strictly adherent to GFD.
      Younger age at diagnosis and shorter duration since the diagnosis were associated
      with a better adherence rate. CONCLUSION: CD has similar clinical presentations
      among Saudi children compared to other parts of the ward; however, the adherence
      to GFD is relatively poor. Younger age at diagnosis and shorter duration since
      the diagnosis were associated with a better adherence rate.

PMID- 25866731
TI  - Availability of blood urea nitrogen/creatinine ratio in gastrointestinal bleeding
      with melena in children.
AB  - PURPOSE: The aims of our study were to evaluate the blood urea nitrogen to
      creatinine ratio (BUN/Cr ratio) for distinguishing between an upper and lower
      gastrointestinal bleeding (GIB), and differentiating between the two most common
      causes of upper gastrointestinal bleeding (UGIB) presenting with melena in
      children. METHODS: Retrospective data of patients with GIB presenting with melena
      were analyzed. The data from 60 cases were reviewed including demographics,
      laboratory findings, diagnostic modalities and results, treatments, and
      transfusions. RESULTS: Among the 60 cases, UGIB and lower gastrointestinal
      bleeding (LGIB) were found in 35 cases (58.3%) and 14 cases (23.3%),
      respectively. The two common causes of UGIB were varices (37.1%), and peptic
      ulcer diseases (PUD) (31.4%). The BUN/Cr ratio of 30 or greater was higher in
      UGIB than LGIB (odds ratio [OR], 6.9; 95% confidence interval [95% CI], 1.3
      37.2). In UGIB, the BUN/Cr ratio of the varices group was higher than that of the
      PUD group (p=0.015). The OR for the BUN/Cr ratio appeared as 1.2 per unit
      increase in the varices group than the PUD group (95% CI, 1.03-1.3). There was no
      difference between the PUD group and Meckel's diverticulum group. CONCLUSION: The
      BUN/Cr ratio was not uneven in differentiating UGIB from LGIB of children with
      melena in our study. This suggests that BUN/Cr ratio should be interpreted
      carefully.

PMID- 25866732
TI  - Laboratory markers indicating gastrointestinal involvement of henoch-schonlein
      purpura in children.
AB  - PURPOSE: To determine clinically useful biochemical markers reflecting disease
      activity and/or gastrointestinal (GI) tract involvement in Henoch-Schonlein
      purpura (HSP). METHODS: A total of 185 children with HSP and 130 controls were
      included. Laboratory data indicating inflammation, standard coagulation, and
      activated coagulation were analyzed for the HSP patients, including measurements
      of the hemoglobin level, white blood cell (WBC) count, absolute neutrophil count
      (ANC), platelet count, erythrocyte sedimentation rate (ESR), C-reactive protein
      (CRP) level, prothrombin time, activated partial thromboplastin time, and
      fibrinogen, D-dimer, and fibrin degradation product (FDP) levels. The clinical
      scores of the skin, joints, abdomen, and kidneys were assessed during the acute
      and convalescence phases of HSP. RESULTS: The WBC count, ANC, ESR, and CRP,
      fibrinogen, D-dimer, and FDP levels were significantly higher in the acute phase
      compared with the convalescent phase of HSP (p<0.05). The total clinical scores
      were more strongly correlated with the D-dimer (r=0.371, p<0.001) and FDP
      (r=0.369, p<0.001) levels than with inflammatory markers, such as the WBC count
      (r=0.241, p=0.001), ANC (r=0.261, p<0.001), and CRP (r=0.260, p<0.001) levels.
      The patients with GI symptoms had significantly higher ANC (median [interquartile
      range], 7,138.0 [4,446.4-9,470.0] vs. 5,534.1 [3,263.0-8,153.5], p<0.05) and CRP
      (0.49 [0.15-1.38] vs. 0.23 [0.01-0.67], p<0.05), D-dimer (2.63 [1.20-4.09] vs.
      1.75 [0.62-3.39]), and FDP (7.10 [0.01-13.65] vs. 0.10 [0.01-7.90], p<0.05)
      levels than those without GI symptoms. CONCLUSION: D-dimer and FDPs are more
      strongly associated with disease activity and more consistently reflect GI
      involvement than inflammatory markers during the acute phase of HSP.

PMID- 25866733
TI  - Liver transplantation for metabolic liver disease: experience at a living donor
      dominant liver transplantation center.
AB  - PURPOSE: Metabolic liver disease (MLD) often progresses to life-threatening
      conditions. This study intends to describe the outcomes of liver transplantation
      (LTx) for MLD at a living donor-dominant transplantation center where potentially
      heterozygous carrier grafts are employed. METHODS: We retrospectively evaluated
      the medical records of 54 patients with MLD who underwent LTx between November
      1995 and February 2012 at Asan Medical Center in Seoul, Korea. The cumulative
      graft and patient survival rates were analyzed according to patient age, and
      living or deceased donor LTx. Recurrence of the original disease was also
      investigated. RESULTS: The post-transplant cumulative patient survival rates at
      one, five, and 10 years were 90.7%, 87.5% and 87.5%, and the graft survival rates
      were 88.8%, 85.5%, and 85.5%, respectively. There were no differences in the
      patient survival rates according to the recipient age, human leukocyte antigen
      matching, and living or deceased donor LTx. There were also no differences in the
      patient survival rates between the MLD and the non-MLD groups for children.
      Recurrence of the original metabolic disease was not observed in any patient
      during the follow-up period. CONCLUSION: Our results suggest that the living
      donor-dominant transplantation program is well-tolerated in MLD without
      recurrence of the original MLD using all types of transplantation.

PMID- 25866734
TI  - Achalasia Previously Diagnosed as Gastroesophageal Reflux Disease by Relying on
      Esophageal Impedance-pH Monitoring: Use of High-Resolution Esophageal Manometry
      in Children.
AB  - Gastroesophageal reflux disorder (GERD) is the most common esophageal disorder in
      children. Achalasia occurs less commonly but has similar symptoms to GERD. A nine
      year old boy presented with vomiting, heartburn, and nocturnal cough. The
      esophageal impedance-pH monitor revealed nonacidic GERD (all-refluxate clearance
      percent time of 20.9%). His symptoms persisted despite medical treatment for
      GERD, and he was lost to follow up. Four years later, he presented with
      heartburn, solid-food dysphagia, daily post-prandial vomiting, and failure to
      thrive. Endoscopy showed a severely dilated esophagus with candidiasis. High
      resolution manometry was performed, and he was diagnosed with classic achalasia
      (also known as type I). His symptoms resolved after two pneumatic dilatation
      procedures, and his weight and height began to catch up to his peers. Clinicians
      might consider using high-resolution manometry in children with atypical GERD
      even after evaluation with an impedance-pH monitor. 

PMID- 25866735
TI  - Disseminated cytomegalovirus infection and protein losing enteropathy as
      presenting feature of pediatric patient with Crohn's disease.
AB  - We report a pediatric patient admitted with abdominal pain, diffuse lower
      extremity edema and watery diarrhea for two months. Laboratory findings including
      complete blood count, serum albumin, lipid and immunoglobulin levels were
      compatible with protein losing enteropathy. Colonoscopic examination revealed
      diffuse ulcers with smooth raised edge (like "punched out holes") in the colon
      and terminal ileum. Histopathological examination showed active colitis,
      ulcerations and inclusion bodies. Immunostaining for cytomegalovirus was
      positive. Despite supportive management, antiviral therapy, the clinical
      condition of the patient worsened and developed disseminated cytomegalovirus
      infection and the patient died. Protein losing enteropathy and disseminated
      cytomegalovirus infection a presenting of feature in steroid-naive patient with
      inflammatory bowel disease is very rare. Hypogammaglobulinemia associated with
      protein losing enteropathy in Crohn's disease may predispose the cytomegalovirus
      infection in previously healthy children. 

PMID- 25866736
TI  - Suppurative meckel diiverticulum in a 3-year-old girl presenting with
      periumbilical cellulitis.
AB  - Meckel diverticulum (MD) is one of the most common congenital gastrointestinal
      anomalies and occurs in 1.2-2% of the general population. MD usually presents
      with massive painless rectal bleeding, intestinal obstruction or inflammation in
      children and adults. Suppurative Meckel diverticulitis is uncommon in children.
      An experience is described of a 3-year-old girl with suppurative inflammation in
      a tip of MD. She complained of acute colicky abdominal pain, vomiting and
      periumbilical erythema. Laparoscopic surgery found a relatively long MD with
      necrotic and fluid-filled cystic end, which was attatched to abdominal wall
      caused by inflammation. Herein, we report an interesting and unusual case of a
      suppurative Meckel diverticulitis presenting as periumbilical cellulitis in a
      child. Because of its varied presentations, MD might always be considered as one
      of the differential diagonosis. 

PMID- 25866737
TI  - Correction: the complex surgical management of the first case of severe combined
      immunodeficiency and multiple intestinal atresias surviving after the fourth year
      of life.
AB  - [This corrects the article on p. 257 in vol. 17, PMID: 25587526.]. 

PMID- 25866739
TI  - Correction.
AB  - [This corrects the article DOI: 10.7860/JCDR/2014/10727.5080.]. 

PMID- 25866738
TI  - The ability of oral & maxillofacial surgeons to perform basic life resuscitation
      in chattisgarh.
AB  - AIM AND OBJECTIVE: This study was conducted to assess the ability of oral &
      maxillofacial surgeons regarding basic life resuscitation in case of medical
      emergencies. MATERIALS AND METHODS: This cross-sectional study was conducted
      among oral & maxillofacial surgeons through a mailed questionnaire. The sample
      size was finalized to 152 including 108 - males and 44 - females with mean age of
      the subjects as 30.65 y. The Statistical software namely SPSS version 16.0 was
      used for data analysis. STATISTICAL ANALYSIS: The student's t-test, ANOVA test
      and post-hoc test were used as tests of significance for statistical evaluation
      at p <= 0.05. RESULTS: The study revealed that most of the participants were
      aware about the administration of drugs. Around half of the surgeons (52.4%) were
      able to understand correct reading of ECG. It has been seen that, 66.8% were
      properly knowing, how to maintain the airway and 77.4% were experienced in the
      administration of oxygen in case of emergencies. Overall the knowledge was more
      among experienced dental surgeons. CONCLUSION: It was found that most of the
      participants were aware to handle the medical emergencies in dental practice and
      the awareness was higher among senior surgeons. Still the surgeon should have
      more knowledge for initial stabilization in a patient with risk happening at
      dental office.

PMID- 25866740
TI  - Diabetes and visual impairment in sub-Saharan Africa: evidence from Cameroon.
AB  - BACKGROUND: "Vision 2020 - the right to sight" is a program which purpose is to
      eliminate avoidable blindness by the year 2020 through the implementation of
      concrete action plans at the national and district levels. Accordingly, baseline
      data are needed for the planning, monitoring, follow-up and evaluation of this
      program. The present study aimed to better characterize visual impairment and
      blindness in Cameroonian diabetics by providing with baseline data on the
      prevalence and main causes of these affections. METHODS: This was a hospital
      based cross-sectional study, conducted from October 2004 to October 2006 at the
      Department of Ophthalmology of the Douala General Hospital, Cameroon. We included
      407 diabetic patients who were referred from diabetes clinics for ophthalmologic
      evaluation. Ophthalmologic data included visual acuity, intra-ocular pressure,
      fundoscopy and fluorescein angiography. RESULTS: The prevalence of blindness and
      poor vision were respectively 12.3% and 17.4% with regard to the worst eyes.
      Fifty nine (14.5%) patients were found with diabetic maculopathy, of whom 25.4%
      (15/59) had poor vision, and 25.4% (15/59) were blind. The prevalence of sight
      threatening retinopathy (severe non-proliferative and proliferative) was 17.4%.
      The degree of visual impairment was comparable in both diabetic types (p =
      0.825), and it increased with the severity of retinopathy (p < 0.0001), as well
      as that of maculopathy (p <0.0001). The prevalence of glaucoma was 15% (61/407)
      when considering the worst eyes. The severity of visual impairment increased with
      the severity of glaucoma (p = 0.001). One hundred and twenty-one (29.7%) patients
      presented with cataract irrespective of its location or severity. Cataract was
      significantly associated with poor vision and blindness (p < 0.0001).
      Hypertensive retinopathy (4.9%), papillary ischaemia (2.7%), vaso-occlusive eye
      disease (2.5%), and age-related macular edema (2%) were the other potential
      causes of visual impairment and blindness encountered the most in our setting.
      Age >= 50 years, male sex, duration of diabetes and hypertension variously
      increased the risk of having glaucoma, cataract, diabetic retinopathy or
      maculopathy. CONCLUSION: Poor vision and blindness are frequent in Cameroonian
      diabetics, and their causes are similar to those reported by various other
      surveys: mainly cataract, glaucoma, diabetic retinopathy and maculopathy.

PMID- 25866741
TI  - Mental health status of patients with mild traumatic brain injury admitted to
      shahid beheshti hospital of kashan, iran.
AB  - BACKGROUND: Planning for providing mental health services to the mentally
      patients due to brain injury need awareness of mental health status of the
      patient. OBJECTIVES: This study aimed to assess the mental health of patients
      with mild TBI. PATIENTS AND METHODS: The descriptive cross-sectional study was
      performed on 286 patients with mild TBI who were admitted to department of
      neurosurgery of Shahid Beheshti Hospital, Kashan, Iran, during the first eight
      months of 2013. Enrolled patients were 15 to 70 years old who able to respond to
      questionnaires. The Brief Symptom Inventory (BSI) questionnaire is used to assess
      the mental health status of the patients. The data were presented using logistic
      regression and descriptive statistics. RESULTS: A total of 286 patients, 79.7%
      males and 20.3% females with male to female ratio of 4:1, completed the study.
      Female had significantly higher Global Severity Index (GSI) compared to males.
      There was a significant association between, psychologic disorders' symptoms and
      age (P = 0.00). The mean (SD) of GSI on the Symptom Checklist-90 (SCL-90) was
      1.39 (0.58). CONCLUSIONS: This study showed that 36% of the patients with mild
      TBI symptoms had mental health problems. Given the high rates of psychologic
      disorders among patients with mild TBI, it is necessary to reduce the factors
      that caused the disorder.

PMID- 25866742
TI  - Histological evaluation of intratumoral myxoma virus treatment in an
      immunocompetent mouse model of melanoma.
AB  - Two recombinant myxoma viruses (MYXV expressing a fluorescent protein [MYXV-Tred]
      and MYXV-Tred encoding murine interleukin-15 [MYXV-IL15]) were evaluated for
      therapeutic effects in an aggressive B16F10 melanoma model in immunocompetent
      mice. It was hypothesized that continuous expression of IL-15 within a tumor
      would recruit cytotoxic effector cells to induce an antitumor immune response and
      improve treatment efficacy. Weekly intratumoral injections were given to evaluate
      the effect of treatment on the median survival time of C57BL/6 mice bearing
      established B16F10 melanomas. Mice that received MYXV-Tred or MYXV-IL15 lived
      significantly longer than mice given treatment controls. Unexpectedly, the median
      survival time of MYXV-IL15-treated mice was similar to that of MYXV-treated mice.
      At 1, 2, and 4 days postinoculation, viral plaque assays detected replicating
      MYXV-Tred and MYXV-IL15 within treated tumors. At these time points in MYXV-IL15
      treated tumors, IL-15 concentration, lymphocyte grades, and cluster of
      differentiation-3+ cell counts were significantly increased when compared to
      other treatment groups. However, viral titers, recombinant protein expression,
      and lymphocyte numbers within the tumors diminished rapidly at 7 days
      postinoculation. These data indicate that treatment with recombinant MYXV should
      be repeated at least every 4 days to maintain recombinant protein expression
      within a murine tumor. Additionally, neutrophilic inflammation was significantly
      increased in MYXV-Tred- and MYXV-IL15-treated tumors at early time points. It is
      speculated that neutrophilic inflammation induced by intratumoral replication of
      recombinant MXYV contributes to the antitumoral effect of MYXV treatment in this
      melanoma model. These findings support the inclusion of neutrophil chemotaxins in
      recombinant poxvirus oncolytic virotherapy.

PMID- 25866743
TI  - Obesity: interactions of genome and nutrients intake.
AB  - Obesity has become one of the major public health problems all over the world.
      Recent novel eras of research are opening for the effective management of obesity
      though gene and nutrient intake interactions because the causes of obesity are
      complex and multifactorial. Through GWASs (genome-wide association studies) and
      genetic variations (SNPs, single nucleotide polymorphisms), as the genetic
      factors are likely to determine individuals' obesity predisposition. The
      understanding of genetic approaches in nutritional sciences is referred as
      "nutrigenomics". Nutrigenomics explores the interaction between genetic factors
      and dietary nutrient intake on various disease phenotypes such as obesity.
      Therefore, this novel approach might suggest a solution for the effective
      prevention and treatment of obesity through individual genetic profiles and help
      improve health conditions. 

PMID- 25866744
TI  - Antioxidant and anticancer activities of broccoli by-products from different
      cultivars and maturity stages at harvest.
AB  - Many studies on broccoli have analyzed the functional components and their
      functionality in terms of antioxidant and anticancer activities; however, these
      studies have focused on the florets of different varieties. Investigation of the
      functionality of broccoli by-products such as leaves, stems, and leaf stems from
      different cultivars and harvest dates might be valuable for utilizing waste
      materials as useful food components. Total phenolics and sulforaphane contents,
      and antioxidant and anticancer activities were measured in the leaves, leaf
      stems, and stems of early-maturing (Kyoyoshi), middle-maturing (Myeongil 96), and
      late-maturing broccoli (SK3-085) at different harvest dates. Total phenolics in
      the leaves of Kyoyoshi were about 1.8-fold to 12.1-fold higher than those in all
      of the other cultivars and parts. The sulforaphane content of Kyoyoshi was 2.8
      fold higher in the stems than in the florets. Antioxidant activities using 2,2
      diphenyl-1-picrylhydrazyl radical scavenging activity and oxygen radical
      absorbance capacity were highest in Kyoyoshi, followed by Myeongil 96 and SK3
      085, most notably in the leaves harvested at the immature stage. Inhibition
      activity of cell growth against the NCI-H1299 cell lines was highest in the
      leaves of all cultivars in decreasing order of florets, leaf stems, and stems.
      The leaves harvested in October (nonflowering stage) had the highest inhibition
      activity, while those harvested in January (mature broccoli) showed the lowest.
      The results of this study demonstrate that broccoli leaves and stems contain high
      levels of total phenolics, and high antioxidant and anticancer activities and can
      provide opportunities for early-maturing broccoli as functional fresh raw
      vegetables. 

PMID- 25866745
TI  - Effect of Standardized Boesenbergia pandurata Extract and Its Active Compound
      Panduratin A on Skin Hydration and Barrier Function in Human Epidermal
      Keratinocytes.
AB  - The skin plays a key role in protecting the body from the environment and from
      water loss. Cornified envelope (CE) and natural moisturizing factor (NMF) are
      considered as the primary regulators of skin hydration and barrier function. The
      CE prevents loss of water from the body and is formed by cross-linking of several
      proteins. Among these proteins, filaggrin is an important protein because NMF is
      produced by the degradation of filaggrin. Proteases, including matriptase and
      prostasin, stimulate the generation of filaggrin from profilaggrin and caspase-14
      plays a role in the degradation of filaggrin. This study elucidated the effects
      of an ethanol extract of Boesenbergia pandurata (Roxb.) Schltr., known as
      fingerroot, and its active compound panduratin A on CE formation and filaggrin
      processing in HaCaT, human epidermal keratinocytes. B. pandurata extract (BPE)
      and panduratin A significantly stimulated not only CE formation but also the
      expression of CE proteins, such as loricrin, involucrin, and transglutaminase,
      which were associated with PPARalpha expression. The mRNA and protein levels of
      filaggrin and filaggrin-related enzymes, such as matriptase, prostasin, and
      caspase-14 were also up-regulated by BPE and panduratin A treatment. These
      results suggest that BPE and panduratin A are potential nutraceuticals which can
      enhance skin hydration and barrier function based on their CE formation and
      filaggrin processing. 

PMID- 25866746
TI  - Antioxidant and Cytoprotective Effects of Lotus (Nelumbo nucifera) Leaves
      Phenolic Fraction.
AB  - Phenolic rich ethyl acetate fraction (EAF) from lotus leaves was prepared and its
      bioactive components, antioxidant and cytoprotective effects were investigated.
      EAF showed high total phenolic content and flavonoid content and contained rutin
      (11,331.3+/-4.5 mg/100 g EAF), catechin (10,853.8+/-5.8 mg/100 g EAF), sinapic
      acid (1,961.3+/-5.6 mg/100 g EAF), chlorogenic acid (631.9+/-2.3 mg/100 g EAF),
      syringic acid (512.3+/-2.5 mg/100 g EAF), and quercetin (415.0+/-2.1 mg/100 g
      EAF). EAF exerted the IC50 of 4.46 MUg/mL and 5.35 MUg/mL toward DPPH and ABTS
      cation radicals, respectively, and showed strong reducing power, which was better
      than that of ascorbic acid, a positive control. Additionally, EAF protected
      hydroxyl radical-induced DNA damage indicated by the conversion of supercoiled
      pBR322 plasmid DNA to the open circular form and inhibited lipid peroxidation of
      polyunsaturated fatty acid in a linoleic acid emulsion. In cultured hepatocytes,
      EAF exerted a cytoprotective effect against oxidative stress by inhibiting
      intracellular reactive oxygen species formation and membrane lipid peroxidation.
      In addition, depletion of glutathione under oxidative stress was remarkably
      restored by treatment with EAF. The results suggest that EAF have great potential
      to be used against oxidative stress-induced health conditions. 

PMID- 25866747
TI  - Anti-Oxidant and Anti-Adipogenic Effects of Ethanol Extracts from Wheat Germ and
      Wheat Germ Fermented with Aspergillus oryzae.
AB  - Most of the wheat germ in cereal grains is removed during the milling process.
      Various physiological effects have been reported for bioactive substances in
      wheat germ such as phenolic acids and flavonoids. In this study, the anti-oxidant
      and anti-adipogenic effects of ethanol extracts from wheat germ (WGE) and wheat
      germ fermented with Aspergillus oryzae (F-WGE) were investigated in HepG2 and 3T3
      L1 cells. The anti-oxidant activity of F-WGE was demonstrated by a dose-dependent
      increase in the enhanced scavenging capacity of hydroxyl radicals and Cu(2+)
      chelating activity compared to WGE. WGE and F-WGE treatment at doses between 10
      and 400 MUg/mL did not affect the viability of HepG2 and 3T3-L1 cells.
      Intracellular ROS levels from Cu(2+)-induced oxidative stress were significantly
      decreased by F-WGE treatment in HepG2 cells compared to WGE. Lipid accumulation
      was increased in 3T3-L1 adipocytes by 100 MUM Fe(2+) treatment, but the
      accumulation was strongly inhibited by 100 MUg/mL of WGE and F-WGE treatment.
      These results suggest that changes in bioactive substances during the
      fermentation of wheat germ can potentiate scavenging activities against
      transition metal-induced oxidative stress and lipid accumulation in 3T3-L1
      adipocytes. Therefore, we propose that F-WGE is a novel food materials and
      provided scientific evidences for its efficacy in the development of functional
      foods. 

PMID- 25866748
TI  - Anti-Fatigue Effects of Fermented Rhodiola rosea Extract in Mice.
AB  - Rhodiola rosea is a perennial plant which grows in the alpine regions of Europe
      and Asia. Although the protective effects of R. rosea extract from fatigue due to
      exercise stress have been reported, studies on fermented R. rosea extract remain
      insufficient to date. Therefore, this study was conducted to examine the
      protective effects of fermented R. rosea extract against fatigue and exercise
      stress. As a result, fermented R. rosea extract was found to significantly
      increase swimming time, hepatic superoxide dismutase content, and serum lactate
      dehydrogenase in mice, while decreasing serum blood urea nitrogen content
      compared to R. rosea extract. Given the above results, it is considered that
      fermented R. rosea extract effectively protects against fatigue caused by
      strenuous exercise. 

PMID- 25866749
TI  - Dietary E-Polylysine Decreased Serum and Liver Lipid Contents by Enhancing Fecal
      Lipid Excretion Irrespective of Increased Hepatic Fatty Acid Biosynthesis-Related
      Enzymes Activities in Rats.
AB  - E-Polylysine (EPL) is used as a natural preservative in food. However, few
      studies have been conducted to assess the beneficial functions of dietary EPL.
      The purpose of this study was to elucidate the mechanism underlying the
      inhibition of neutral and acidic sterol absorption and hepatic enzyme activity
      related fatty acid biosynthesis following EPL intake. EPL digest prepared using
      an in vitro digestion model had lower lipase activity and micellar lipid
      solubility and higher bile acid binding capacity than casein digest. Male Wistar
      rats were fed an AIN-93G diet containing 1% (wt/wt) EPL or l-lysine. After 4
      weeks of feeding these diets, the marked decrease in serum and liver
      triacylglycerol contents by the EPL diet was partly attributed to increased fecal
      fatty acid excretion. The activities of hepatic acetyl-coenzyme A carboxylase and
      glucose-6-phosphate dehydrogenase, which are key enzymes of fatty acid
      biosynthesis, were enhanced in rats fed EPL diet. The increased fatty acid
      biosynthesis activity due to dietary EPL may be prevented by the enhancement of
      fecal fatty acid excretion. The hypocholesterolemic effect of EPL was mediated by
      increased fecal neutral and acidic sterol excretions due to the EPL digest
      suppressing micellar lipid solubility and high bile acid binding capacity. These
      results show that dietary EPL has beneficial effects that could help prevent
      lifestyle-related diseases such as hyperlipidemia and atherosclerosis. 

PMID- 25866750
TI  - Preventive Effect of the Korean Traditional Health Drink (Taemyeongcheong) on
      Acetaminophen-Induced Hepatic Damage in ICR Mice.
AB  - This study was to investigate the preventive effect of taemyeongcheong (TMC, a
      Korean traditional health drink) on acetaminophen (APAP, 800 mg/kg BW)-induced
      hepatic damage in ICR mice. TMC is prepared from Saururus chinensis, Taraxacum
      officinale, Zingiber officinale, Cirsium setidens, Salicornia herbacea, and
      Glycyrrhizae. A high dose of TMC (500 mg/kg BW) was found to decrease APAP
      induced increases in serum levels of alanine aminotransferase, aspartate
      aminotransferase, alkaline phosphatase, and lactate dehydrogenase. TMC
      pretreatment also increased the hepatic levels of hepatic catalase, superoxide
      dismutase, glutathione peroxidase, and glutathione, and reduced serum levels of
      the inflammatory cytokines tumor necrosis factor (TNF)-alpha and interleukin (IL)
      6 in mice administered APAP (P<0.05). TMC (500 mg/kg BW) reduced hepatic mRNA
      levels of TNF-alpha, IL-1beta, IL-6, COX-2, and iNOS by 87%, 84%, 89%, 85%, and
      88%, respectively, in mice treated with APAP (P<0.05). Furthermore, histological
      observations suggested TMC pretreatment dose-dependently prevented APAP-induced
      hepatocyte damage. These results suggest that TMC could be used as a functional
      health drink to prevent hepatic damage. 

PMID- 25866751
TI  - The study of heat penetration of kimchi soup on stationary and rotary retorts.
AB  - The aim of this study was to determine the heat-penetration characteristics using
      stationary and rotary retorts to manufacture Kimchi soup. Both heat-penetration
      tests and computer simulation based on mathematical modeling were performed. The
      sterility was measured at five different positions in the pouch. The results
      revealed only a small deviation of F 0 among the different positions, and the
      rate of heat transfer was increased by rotation of the retort. The thermal
      processing of retort-pouched Kimchi soup was analyzed mathematically using a
      finite-element model, and optimum models for predicting the time course of the
      temperature and F 0 were developed. The mathematical models could accurately
      predict the actual heat penetration of retort-pouched Kimchi soup. The average
      deviation of the temperature between the experimental and mathematical predicted
      model was 2.46% (R(2)=0.975). The changes in nodal temperature and F 0 caused by
      microbial inactivation in the finite-element model predicted using the NISA
      program were very similar to that of the experimental data of for the retorted
      Kimchi soup during sterilization with rotary retorts. The correlation coefficient
      between the simulation using the NISA program and the experimental data was very
      high, at 99%. 

PMID- 25866752
TI  - Biofunctional properties of enzymatic squid meat hydrolysate.
AB  - Squid is one of the most important commercial fishes in the world and is mainly
      utilized or consumed as sliced raw fish or as processed products. The
      biofunctional activities of enzymatic squid meat hydrolysate were determined to
      develop value-added products. Enzymatic squid hydrolysate manufactured by
      Alcalase effectively quenched 1,1-diphenyl-2-picrylhydrazyl radical, hydroxyl
      radical, and hydrogen peroxide radical with IC50 values of 311, 3,410, and 111.5
      MUg/mL, respectively. Angiotensin I-converting enzyme inhibitory activity of
      squid hydrolysate was strong with an IC50 value of 145.1 MUg/mL, while tyrosinase
      inhibitory activity with an IC50 value of 4.72 mg/mL was moderately low. Overall,
      squid meat hydrolysate can be used in food or cosmetic industries as a bioactive
      ingredient and possibly be used in the manufacture of seasoning, bread, noodle,
      or cosmetics. 

PMID- 25866753
TI  - Differential Effects of Methoxylated p-Coumaric Acids on Melanoma in B16/F10
      Cells.
AB  - As an approach to search for chemopreventive agents, we tested p-coumaric acid, 3
      methoxy-p-coumaric acid (ferulic acid), and 3,5-dimethoxy-p-coumaric acid
      (sinapic acid) in B16/F10 melanoma cells. Intracellular melanin contents were
      determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay
      and cytotoxicity of the compounds were examined by lactate dehydrogenase (LDH)
      release. p-Coumaric acid showed inhibitory effect on melanogenesis, but ferulic
      acid increased melanin content, and sinapic acid had almost no effect on
      melanogenesis. Treatment with ferulic acid resulted in a 2 to 3 fold elevation in
      the production of melanin. Correlatively, cell viability decreased in a dose
      dependent manner when treated with ferulic acid. However, ferulic acid did not
      affect the LDH release from the cells. Treatment with sinapic acid resulted in a
      50~60% elevation in the release of LDH when treated with a 200 MUg/mL
      concentration and showed neither cytostasis nor increase of melanin synthesis in
      a dose-dependent manner. Taken together, p-coumaric acid inhibits melanogenesis,
      ferulic acid induces melanogenesis, and sinapic acid exerts cytotoxic effects in
      B16/F10 murine melanoma cells. The results indicate that the addition of methoxy
      groups to p-coumaric acid shows the melanogenic or cytotoxic effects in melanoma
      cells compared to the original compound. Therefore, this study suggests the
      possibility that methoxylated p-coumaric acid, ferulic acid can be used as a
      chemopreventive agent. 

PMID- 25866754
TI  - A Novel Lactobacillus casei LP1 Producing 1,4-Dihydroxy-2-Naphthoic Acid, a
      Bifidogenic Growth Stimulator.
AB  - 1,4-Dihydroxy-2-naphthoic acid (DHNA) is a bifidogenic growth stimulator (BGS)
      and could be a functional food ingredient since bifidobacteria are beneficial for
      human health. For that reason, lactic acid bacteria producing DHNA have been
      screened. A lactic acid bacterium LP1 strain isolated from a natural cheese was
      confirmed to produce DHNA, analyzed by a HPLC method. The strain was identified
      as Lactobacillus casei by 16S rRNA gene sequence analysis. The cell-free
      supernatant of fermented whey produced by L. casei LP1 presented the BGS activity
      for three bifidobacterial strains such as Bifidobacterium longum subsp. infantis
      KCTC 3127, Bifidobacterium bifidum KCTC 3202, and Bifidobacterium breve KCTC 3220
      which were human-originated. To the best of our knowledge, a L. casei strain
      which can produce DHNA was firstly identified in this study. 

PMID- 25866755
TI  - Protecting intestinal epithelial cell number 6 against fission neutron
      irradiation through NF-kappaB signaling pathway.
AB  - The purpose of this paper is to explore the change of NF-kappaB signaling pathway
      in intestinal epithelial cell induced by fission neutron irradiation and the
      influence of the PI3K/Akt pathway inhibitor LY294002. Three groups of IEC-6 cell
      lines were given: control group, neutron irradiation of 4 Gy group, and neutron
      irradiation of 4 Gy with LY294002 treatment group. Except the control group, the
      other groups were irradiated by neutron of 4 Gy. LY294002 was given before 24
      hours of neutron irradiation. At 6 h and 24 h after neutron irradiation, the
      morphologic changes, proliferation ability, apoptosis, and necrosis rates of the
      IEC-6 cell lines were assayed and the changes of NF-kappaB and PI3K/Akt pathway
      were detected. At 6 h and 24 h after neutron irradiation of 4 Gy, the
      proliferation ability of the IEC-6 cells decreased and lots of apoptotic and
      necrotic cells were found. The injuries in LY294002 treatment and neutron
      irradiation group were more serious than those in control and neutron irradiation
      groups. The results suggest that IEC-6 cells were obviously damaged and induced
      serious apoptosis and necrosis by neutron irradiation of 4Gy; the NF-kappaB
      signaling pathway in IEC-6 was activated by neutron irradiation which could
      protect IEC-6 against injury by neutron irradiation; LY294002 could inhibit the
      activity of IEC-6 cells.

PMID- 25866756
TI  - Parkinsonism in spinocerebellar ataxia.
AB  - Spinocerebellar ataxia (SCA) presents heterogeneous clinical phenotypes, and
      parkinsonism is reported in diverse SCA subtypes. Both levodopa responsive
      Parkinson disease (PD) like phenotype and atypical parkinsonism have been
      described especially in SCA2, SCA3, and SCA17 with geographic differences in
      prevalence. SCA2 is the most frequently reported subtype of SCA related to
      parkinsonism worldwide. Parkinsonism in SCA2 has unique genetic characteristics,
      such as low number of expansions and interrupted structures, which may explain
      the sporadic cases with low penetrance. Parkinsonism in SCA17 is more remarkable
      in Asian populations especially in Korea. In addition, an unclear cutoff of the
      pathologic range is the key issue in SCA17 related parkinsonism. SCA3 is more
      common in western cohorts. SCA6 and SCA8 have also been reported with a PD-like
      phenotype. Herein, we reviewed the epidemiologic, clinical, genetic, and
      pathologic features of parkinsonism in SCAs. 

PMID- 25866758
TI  - A time-series model of phase amplitude cross frequency coupling and comparison of
      spectral characteristics with neural data.
AB  - Stochastic processes that exhibit cross-frequency coupling (CFC) are introduced.
      The ability of these processes to model observed CFC in neural recordings is
      investigated by comparison with published spectra. One of the proposed models,
      based on multiplying a pulsatile function of a low-frequency oscillation (theta)
      with an unobserved and high-frequency component, yields a process with a spectrum
      that is consistent with observation. Other models, such as those employing a
      biphasic pulsatile function of a low-frequency oscillation, are demonstrated to
      be less suitable. We introduce the full stochastic process time series model as a
      summation of three component weak-sense stationary (WSS) processes, namely,
      theta, gamma, and eta, with eta a 1/f (alpha) noise process. The gamma process is
      constructed as a product of a latent and unobserved high-frequency process x with
      a function of the lagged, low-frequency oscillatory component (theta). After
      demonstrating that the model process is WSS, an appropriate method of simulation
      is introduced based upon the WSS property. This work may be of interest to
      researchers seeking to connect inhibitory and excitatory dynamics directly to
      observation in a model that accounts for known temporal dependence or to
      researchers seeking to examine what can occur in a multiplicative time-domain CFC
      mechanism. 

PMID- 25866757
TI  - The role of ovarian sex steroids in metabolic homeostasis, obesity, and
      postmenopausal breast cancer: molecular mechanisms and therapeutic implications.
AB  - Obese postmenopausal women have an increased risk of breast cancer and are likely
      to have a worse prognosis than nonobese postmenopausal women. The cessation of
      ovarian function after menopause results in withdrawal of ovarian sex steroid
      hormones, estrogen, and progesterone. Accumulating evidence suggests that the
      withdrawal of estrogen and progesterone causes homeostasis imbalances, including
      decreases in insulin sensitivity and leptin secretion and changes in glucose and
      lipid metabolism, resulting in a total reduction in energy expenditure. Together
      with a decrease in physical activity and consumption of a high fat diet, these
      factors significantly contribute to obesity in postmenopausal women. Obesity may
      contribute to breast cancer development through several mechanisms. Obesity
      causes localized inflammation, an increase in local estrogen production, and
      changes in cellular metabolism. In addition, obese women have a higher risk of
      insulin insensitivity, and an increase in insulin and other growth factor
      secretion. In this review, we describe our current understanding of the molecular
      actions of estrogen and progesterone and their contributions to cellular
      metabolism, obesity, inflammation, and postmenopausal breast cancer. We also
      discuss how modifications of estrogen and progesterone actions might be used as a
      therapeutic approach for obesity and postmenopausal breast cancer. 

PMID- 25866759
TI  - The date palm tree rhizosphere is a niche for plant growth promoting bacteria in
      the oasis ecosystem.
AB  - In arid ecosystems environmental factors such as geoclimatic conditions and
      agricultural practices are of major importance in shaping the diversity and
      functionality of plant-associated bacterial communities. Assessing the influence
      of such factors is a key to understand (i) the driving forces determining the
      shape of root-associated bacterial communities and (ii) the plant growth
      promoting (PGP) services they provide. Desert oasis environment was chosen as
      model ecosystem where agriculture is possible by the microclimate determined by
      the date palm cultivation. The bacterial communities in the soil fractions
      associated with the root system of date palms cultivated in seven oases in
      Tunisia were assessed by culture-independent and dependent approaches. According
      to 16S rRNA gene PCR-DGGE fingerprinting, the shapes of the date palm rhizosphere
      bacterial communities correlate with geoclimatic features along a north-south
      aridity transect. Despite the fact that the date palm root bacterial community
      structure was strongly influenced by macroecological factors, the potential
      rhizosphere services reflected in the PGP traits of isolates screened in vitro
      were conserved among the different oases. Such services were exerted by the 83%
      of the screened isolates. The comparable numbers and types of PGP traits indicate
      their importance in maintaining the plant functional homeostasis despite the
      different environmental selection pressures. 

PMID- 25866760
TI  - Switching the sphingolipid rheostat in the treatment of diabetes and cancer
      comorbidity from a problem to an advantage.
AB  - Cancer and diabetes are among the most common diseases in western societies.
      Epidemiological studies have shown that diabetic patients have a significantly
      higher risk of developing a number of different types of cancers and that
      individuals with comorbidity (cancer and diabetes/prediabetes) have a poorer
      prognosis relative to nondiabetic cancer patients. The increasing frequency of
      comorbidity of cancer and diabetes mellitus, mainly type 2 diabetes, has driven
      the development of therapeutic interventions that target both disease states.
      There is strong evidence to suggest that balancing the sphingolipid rheostat,
      ceramide--sphingosine--sphingosine-1-phosphate (S1P) is crucial in the prevention
      of diabetes and cancer and sphingosine kinase/S1P modulators are currently under
      development for the treatment of cancer and diabetes. This paper will highlight
      some of the complexities inherent in the use of the emerging sphingosine
      kinase/S1P modulators in the treatment of comorbidity of diabetes and cancer.

PMID- 25866761
TI  - Thyroid hormone and P-glycoprotein in tumor cells.
AB  - P-glycoprotein (P-gp; multidrug resistance pump 1, MDR1; ABCB1) is a plasma
      membrane efflux pump that when activated in cancer cells exports chemotherapeutic
      agents. Transcription of the P-gp gene (MDR1) and activity of the P-gp protein
      are known to be affected by thyroid hormone. A cell surface receptor for thyroid
      hormone on integrin alphavbeta3 also binds tetraiodothyroacetic acid (tetrac), a
      derivative of L-thyroxine (T4) that blocks nongenomic actions of T4 and of 3,5,3'
      triiodo-L-thyronine (T3) at alphavbeta3. Covalently bound to a nanoparticle,
      tetrac as nanotetrac acts at the integrin to increase intracellular residence
      time of chemotherapeutic agents such as doxorubicin and etoposide that are
      substrates of P-gp. This action chemosensitizes cancer cells. In this review, we
      examine possible molecular mechanisms for the inhibitory effect of nanotetrac on
      P-gp activity. Mechanisms for consideration include cancer cell acidification via
      action of tetrac/nanotetrac on the Na(+)/H(+) exchanger (NHE1) and hormone
      analogue effects on calmodulin-dependent processes and on interactions of P-gp
      with epidermal growth factor (EGF) and osteopontin (OPN), apparently via
      alphavbeta3. Intracellular acidification and decreased H(+) efflux induced by
      tetrac/nanotetrac via NHE1 is the most attractive explanation for the actions on
      P-gp and consequent increase in cancer cell retention of chemotherapeutic agent
      ligands of MDR1 protein. 

PMID- 25866762
TI  - Bladder carcinoma data with clinical risk factors and molecular markers: a
      cluster analysis.
AB  - Bladder cancer occurs in the epithelial lining of the urinary bladder and is
      amongst the most common types of cancer in humans, killing thousands of people a
      year. This paper is based on the hypothesis that the use of clinical and
      histopathological data together with information about the concentration of
      various molecular markers in patients is useful for the prediction of outcomes
      and the design of treatments of nonmuscle invasive bladder carcinoma (NMIBC). A
      population of 45 patients with a new diagnosis of NMIBC was selected. Patients
      with benign prostatic hyperplasia (BPH), muscle invasive bladder carcinoma
      (MIBC), carcinoma in situ (CIS), and NMIBC recurrent tumors were not included due
      to their different clinical behavior. Clinical history was obtained by means of
      anamnesis and physical examination, and preoperative imaging and urine cytology
      were carried out for all patients. Then, patients underwent conventional
      transurethral resection (TURBT) and some proteomic analyses quantified the
      biomarkers (p53, neu, and EGFR). A postoperative follow-up was performed to
      detect relapse and progression. Clusterings were performed to find groups with
      clinical, molecular markers, histopathological prognostic factors, and statistics
      about recurrence, progression, and overall survival of patients with NMIBC. Four
      groups were found according to tumor sizes, risk of relapse or progression, and
      biological behavior. Outlier patients were also detected and categorized
      according to their clinical characters and biological behavior. 

PMID- 25866763
TI  - Could alpha-synuclein amyloid-like aggregates trigger a prionic neuronal
      invasion?
AB  - Parkinson's disease (PD), a progressive neurodegenerative disease primarily
      affecting voluntary and controlled movement, is characterized by abnormal
      accumulations of alpha-synuclein (alpha-syn) in intraneuronal Lewy bodies. In the
      last years, the increased number of evidences from both the in vitro and in vivo
      studies has shown the ability of alpha-syn to misfold in amyloid conformations
      and to spread via neuron-to-neuron transmission, suggesting a prion-like
      behaviour. However, in contrast to prion protein (PrP), alpha-syn transmission is
      far from neuronal invasion. The high neuronal toxicity of both mature fibres and
      oligomeric species, as well as the intracellular localization of the protein and
      the difficulty to be secreted, could be key factors impeding the prion ability of
      alpha-syn aggregates. 

PMID- 25866764
TI  - Construction of a CXCL12-KDEL fusion gene to inhibit head and neck squamous cell
      carcinoma metastasis by intracellular sequestration of CXCR4.
AB  - The CXCL12-CXCR4 biological axis consisting of the chemotactic factor CXCL12 and
      its specific receptor CXCR4 plays an important role in oral cancer metastasis.
      High expression of CXCR4 may help oral squamous cancer cells invade local tissues
      and metastasize to lymph nodes. No obvious association was observed between
      CXCL12 expression and lymph node metastasis, suggesting that CXCL12 chemotaxis
      may only be related to CXCR4 expression on the tumor cell membrane. KDEL can be
      retained by receptors on the surface of the intracellular endoplasmic reticulum
      (ER) and also be called an ER retention signal sequence. So we adopted the KDEL
      sequence in this study to generate a CXCL12-KDEL fusion protein in combination
      with a traceable E-tag label. As such, CXCL12 was retained in the ER. Specific
      receptor CXCR4 binds to the CXCL12-KDEL, was also retained in the ER, and was
      thus prevented from reaching the oral squamous cancer cell surface. We reduced
      the cell surface level of CXCR4 and called the technique "intracellular
      sequestration." By this way, we have finished blocking of CXCL12-CXCR4 biological
      axis and inhibiting lymph node metastasis of oral carcinoma. 

PMID- 25866765
TI  - Role of microorganisms present in dairy fermented products in health and disease.

PMID- 25866766
TI  - The expression and distributions of ANP32A in the developing brain.
AB  - Acidic (leucine-rich) nuclear phosphoprotein 32 family, member A (ANP32A), has
      multiple functions involved in neuritogenesis, transcriptional regulation, and
      apoptosis. However, whether ANP32A has an effect on the mammalian developing
      brain is still in question. In this study, it was shown that brain was the organ
      that expressed the most abundant ANP32A by human multiple tissue expression (MTE)
      array. The distribution of ANP32A in the different adult brain areas was diverse
      dramatically, with high expression in cerebellum, temporal lobe, and cerebral
      cortex and with low expression in pons, medulla oblongata, and spinal cord. The
      expression of ANP32A was higher in the adult brain than in the fetal brain of not
      only humans but also mice in a time-dependent manner. ANP32A signals were
      dispersed accordantly in embryonic mouse brain. However, ANP32A was abundant in
      the granular layer of the cerebellum and the cerebral cortex when the mice were
      growing up, as well as in the Purkinje cells of the cerebellum. The variation of
      expression levels and distribution of ANP32A in the developing brain would imply
      that ANP32A may play an important role in mammalian brain development, especially
      in the differentiation and function of neurons in the cerebellum and the cerebral
      cortex. 

PMID- 25866767
TI  - Occurrence of West Nile virus antibodies in wild birds, horses, and humans in
      Poland.
AB  - Serum samples of 474 wild birds, 378 horses, and 42 humans with meningitis and
      lymphocytic meningitis were collected between 2010 and 2014 from different areas
      of Poland. West Nile virus (WNV) antibodies were detected using competition
      enzyme linked immunosorbent assays: ELISA-1 ID Screen West Nile Competition,
      IDvet, ELISA-2 ID Screen West Nile IgM Capture, and ELISA-3 Ingezim West Nile
      Compac. The antibodies were found in 63 (13.29%) out of 474 wild bird serum
      samples and in one (0.26%) out of 378 horse serum samples. Fourteen (33.33%) out
      of 42 sera from patients were positive against WNV antigen and one serum was
      doubtful. Positive samples obtained in birds were next retested with virus
      microneutralisation test to confirm positive results and cross-reactions with
      other antigens of the Japanese encephalitis complex. We suspect that positive
      serological results in humans, birds, and horses indicate that WNV can be somehow
      closely related with the ecosystem in Poland. 

PMID- 25866769
TI  - Identification of the alternative splicing of the UL49 locus of human
      cytomegalovirus.
AB  - The UL49 ORF of human cytomegalovirus (HCMV) is essential for viral replication;
      conserved among all herpes viruses; however, the function is unclear. Once the
      UL49 ORF was precisely deleted from the start to stop codon, the mutant did not
      yield infectious progeny. In this study, we find out many alternatively processed
      ESTs in UL49 locus in HCMV-infected cells, in which there are two novel
      transcription termination sites in UL49 locus. Most of these ESTs are rare
      transcripts that contain directed repeat sequences in the intron splicing
      regions. There is a typical GU-AG intron splicing site in UL49Y transcripts. The
      1847 bp UL49Y cDNA spans an ORF from 335 to 1618 and encodes a putative protein
      of 427 amino acids with a predicted molecular mass of 47.1 kDa. All the new EST
      sequences and UL49Y cDNA sequence have been deposited in the GenBank database
      (GenBank Accession nos. GW314860-GW314900 and GU376796). This study provides us
      with very important clues for revealing the importance of the UL49 locus
      alternative splicing.

PMID- 25866770
TI  - Variability of TKR knee kinematics and relationship with gait kinetics:
      implications for total knee wear.
AB  - Several factors, including compressive load and knee kinematics, have been shown
      to influence wear. External knee moments (a surrogate for load) have recently
      been correlated with the medial and lateral wear scar areas of an unconstrained,
      PCL retaining knee design. Therefore, the purpose of this study was to determine
      whether differences in kinetics during level walking are accompanied by specific
      differences in relative knee kinematics. Thirty TKR patients were gait tested
      using the point cluster technique to obtain 3D motions of the knee. External knee
      moments were calculated from ground reaction forces recorded with a
      multicomponent force plate. The subjects were separated into two distinct
      anteroposterior (AP) motion categories: a low motion group and a high motion
      group. Similarly, the low and high motion groups for internal-external (IE)
      rotation were also identified. For the IE motion, there was no significant
      difference between the transverse internal rotation moments between the two IE
      motion groups. However for the AP motion groups, a higher external peak flexion
      moment was found for the group displaying less AP motion. These observations
      suggest that subjects with higher joint moments execute smaller ranges of AP
      motion and thus are likely to incur less wear. 

PMID- 25866768
TI  - Obesity and cancer progression: is there a role of fatty acid metabolism?
AB  - Currently, there is renewed interest in elucidating the metabolic characteristics
      of cancer and how these characteristics may be exploited as therapeutic targets.
      Much attention has centered on glucose, glutamine and de novo lipogenesis, yet
      the metabolism of fatty acids that arise from extracellular, as well as
      intracellular, stores as triacylglycerol has received much less attention. This
      review focuses on the key pathways of fatty acid metabolism, including uptake,
      esterification, lipolysis, and mitochondrial oxidation, and how the regulators of
      these pathways are altered in cancer. Additionally, we discuss the potential link
      that fatty acid metabolism may serve between obesity and changes in cancer
      progression. 

PMID- 25866771
TI  - In vitro antimicrobial and modulatory activity of the natural products silymarin
      and silibinin.
AB  - Silymarin is a standardized extract from the dried seeds of the milk thistle
      (Silybum marianum L. Gaertn.) clinically used as an antihepatotoxic agent. The
      aim of this study was to investigate the antibacterial and antifungal activity of
      silymarin and its major constituent (silibinin) against different microbial
      strains and their modulatory effect on drugs utilized in clinical practice.
      Silymarin demonstrated antimicrobial activity of little significance against the
      bacterial strains tested, with MIC (minimum inhibitory concentration) values of
      512 ug/mL. Meanwhile, silibinin showed significant activity against Escherichia
      coli with a MIC of 64 ug/mL. The results for the antifungal activity of silymarin
      and silibinin demonstrated a MIC of 1024 ug/mL for all strains. Silymarin and
      silibinin appear to have promising potential, showing synergistic properties when
      combined with antibacterial drugs, which should prompt further studies along this
      line.

PMID- 25866772
TI  - Effect of celastrol on growth inhibition of prostate cancer cells through the
      regulation of hERG channel in vitro.
AB  - OBJECTIVE: To explore the antiprostate cancer effects of Celastrol on prostate
      cancer cells' proliferation, apoptosis, and cell cycle distribution, as well as
      the correlation to the regulation of hERG. METHODS: DU145 cells were treated with
      various concentrations of Celastrol (0.25-16.0 MUmol/L) for 0-72 hours. MTT assay
      was used to evaluate the inhibition effect of Celastrol on the growth of DU145
      cells. Cell apoptosis was detected through both Annexin-V FITC/PI double-labeled
      cytometry and Hoechst 33258. Cell cycle regulation was examined by a propidium
      iodide method. Western blot and RT-PCR technologies were applied to assess the
      expression level of hERG in DU145 cells. RESULTS: Celastrol presented striking
      growth inhibition and apoptosis induction potency on DU145 cells in vitro in a
      time- and dose-dependent manner. The IC50 value of Celastrol for 24 hours was
      2.349 +/- 0.213 MUmol/L. Moreover, Celastrol induced DU145 cell apoptosis in a
      cell cycle-dependent manner, which means Celastrol could arrest DU145 cells in
      G0/G1 phase; accordingly, cells in S phase decreased gradually and no obvious
      changes were found in G2/M phase cells. Through transmission electron microscope,
      apoptotic bodies containing nuclear fragments were found in Celastrol-treated
      DU145 cells. Overexpression of hERG channel was found in DU145 cells, while
      Celastrol could downregulate it at both protein and mRNA level in a dose
      dependent manner (P < 0.01). CONCLUSIONS: Celastrol exhibits its antiprostate
      cancer effects partially through the downregulation of the expression level of
      hERG channel in DU145 cells, suggesting that Celastrol may be a potential agent
      against prostate cancer with a mechanism of blocking the hERG channel.

PMID- 25866773
TI  - Prediction of cancer proteins by integrating protein interaction, domain
      frequency, and domain interaction data using machine learning algorithms.
AB  - Many proteins are known to be associated with cancer diseases. It is quite often
      that their precise functional role in disease pathogenesis remains unclear. A
      strategy to gain a better understanding of the function of these proteins is to
      make use of a combination of different aspects of proteomics data types. In this
      study, we extended Aragues's method by employing the protein-protein interaction
      (PPI) data, domain-domain interaction (DDI) data, weighted domain frequency score
      (DFS), and cancer linker degree (CLD) data to predict cancer proteins.
      Performances were benchmarked based on three kinds of experiments as follows: (I)
      using individual algorithm, (II) combining algorithms, and (III) combining the
      same classification types of algorithms. When compared with Aragues's method, our
      proposed methods, that is, machine learning algorithm and voting with the
      majority, are significantly superior in all seven performance measures. We
      demonstrated the accuracy of the proposed method on two independent datasets. The
      best algorithm can achieve a hit ratio of 89.4% and 72.8% for lung cancer dataset
      and lung cancer microarray study, respectively. It is anticipated that the
      current research could help understand disease mechanisms and diagnosis. 

PMID- 25866774
TI  - New insights into glomerular parietal epithelial cell activation and its
      signaling pathways in glomerular diseases.
AB  - The glomerular parietal epithelial cells (PECs) have aroused an increasing
      attention recently. The proliferation of PECs is the main feature of crescentic
      glomerulonephritis; besides that, in the past decade, PEC activation has been
      identified in several types of noninflammatory glomerulonephropathies, such as
      focal segmental glomerulosclerosis, diabetic glomerulopathy, and membranous
      nephropathy. The pathogenesis of PEC activation is poorly understood; however, a
      few studies delicately elucidate the potential mechanisms and signaling pathways
      implicated in these processes. In this review we will focus on the latest
      observations and concepts about PEC activation in glomerular diseases and the
      newest identified signaling pathways in PEC activation. 

PMID- 25866776
TI  - Effects of extrusion pretreatment parameters on sweet sorghum bagasse enzymatic
      hydrolysis and its subsequent conversion into bioethanol.
AB  - Second-generation bioethanol production from sweet sorghum bagasse first extruded
      at different conditions and then treated with cell wall degrading enzymes and
      fermented with I. orientalis was determined. The twin extruder parameters tested
      were barrel temperature, screws speed, and feedstock moisture content using
      surface response methodology. The best extrusion conditions were 100 degrees C,
      200 rpm, and 30% conditioning moisture content. This nonchemical and continuous
      pretreatment did not generate inhibitory compounds. The extruded feedstocks were
      saccharified varying the biocatalysis time and solids loading. The best
      conditions were 20% solids loading and 72 h of enzymatic treatment. These
      particular conditions converted 70% of the total fibrous carbohydrates into total
      fermentable C5 and C6 sugars. The extruded enzymatically hydrolyzed sweet sorghum
      bagasse was fermented with the strain I. orientalis at 12% solids obtaining a
      yield of 198.1 mL of ethanol per kilogram of bagasse (dw).

PMID- 25866775
TI  - Blood brain barrier: a challenge for effectual therapy of brain tumors.
AB  - Brain tumors are one of the most formidable diseases of mankind. They have only a
      fair to poor prognosis and high relapse rate. One of the major causes of extreme
      difficulty in brain tumor treatment is the presence of blood brain barrier (BBB).
      BBB comprises different molecular components and transport systems, which in turn
      create efflux machinery or hindrance for the entry of several drugs in brain.
      Thus, along with the conventional techniques, successful modification of drug
      delivery and novel therapeutic strategies are needed to overcome this obstacle
      for treatment of brain tumors. In this review, we have elucidated some critical
      insights into the composition and function of BBB and along with it we have
      discussed the effective methods for delivery of drugs to the brain and
      therapeutic strategies overcoming the barrier. 

PMID- 25866778
TI  - Cardiopulmonary response to exercise in COPD and overweight patients:
      relationship between unloaded cycling and maximal oxygen uptake profiles.
AB  - Cardiopulmonary response to unloaded cycling may be related to higher workloads.
      This was assessed in male subjects: 18 healthy sedentary subjects (controls), 14
      hypoxemic patients with chronic obstructive pulmonary disease (COPD), and 31
      overweight individuals (twelve were hypoxemic). They underwent an incremental
      exercise up to the maximal oxygen uptake (VO2max), preceded by a 2 min unloaded
      cycling period. Oxygen uptake (VO2), heart rate (HR), minute ventilation (VE),
      and respiratory frequency (fR) were averaged every 10 s. At the end of unloaded
      cycling period, HR increase was significantly accentuated in COPD and hypoxemic
      overweight subjects (resp., +14 +/- 2 and +13 +/- 1.5 min(-1), compared to +7.5
      +/- 1.5 min(-1) in normoxemic overweight subjects and +8 +/- 1.8 min(-1) in
      controls). The fR increase was accentuated in all overweight subjects (hypoxemic:
      +4.5 +/- 0.8; normoxemic: +3.9 +/- 0.7 min(-1)) compared to controls (+2.5 +/-
      0.8 min(-1)) and COPDs (+2.0 +/- 0.7 min(-1)). The plateau VE increase during
      unloaded cycling was positively correlated with VE values measured at the
      ventilatory threshold and VO2max. Measurement of ventilation during unloaded
      cycling may serve to predict the ventilatory performance of COPD patients and
      overweight subjects during an exercise rehabilitation program.

PMID- 25866779
TI  - The construction of common and specific significance subnetworks of Alzheimer's
      disease from multiple brain regions.
AB  - Alzheimer's disease (AD) is a progressively and fatally neurodegenerative
      disorder and leads to irreversibly cognitive and memorial damage in different
      brain regions. The identification and analysis of the dysregulated pathways and
      subnetworks among affected brain regions will provide deep insights for the
      pathogenetic mechanism of AD. In this paper, commonly and specifically
      significant subnetworks were identified from six AD brain regions. Protein
      protein interaction (PPI) data were integrated to add molecular biological
      information to construct the functional modules of six AD brain regions by Heinz
      algorithm. Then, the simulated annealing algorithm based on edge weight is
      applied to predicting and optimizing the maximal scoring networks for common and
      specific genes, respectively, which can remove the weak interactions and add the
      prediction of strong interactions to increase the accuracy of the networks. The
      identified common subnetworks showed that inflammation of the brain nerves is one
      of the critical factors of AD and calcium imbalance may be a link among several
      causative factors in AD pathogenesis. In addition, the extracted specific
      subnetworks for each brain region revealed many biologically functional
      mechanisms to understand AD pathogenesis. 

PMID- 25866780
TI  - In vivo evaluation of TNF-alpha in the lungs of patients affected by sarcoidosis.
AB  - INTRODUCTION: Sarcoidosis is a multisystemic granulomatous disorder characterized
      by multiple noncaseating granulomas involving intrathoracic lymph nodes and lung
      parenchyma. Recently, the use of anti-tumor necrosis factor alpha (anti-TNFalpha)
      agents has been introduced for therapy of chronic and refractory sarcoidosis with
      controversial results. Infliximab (Remicade) is a chimeric monoclonal antibody
      (mAb) that recognizes and binds TNFalpha, neutralizing its biological effects. In
      the present study,   (99m)Tc labelled infliximab was used to study the expression
      of TNFalpha in sarcoid lesions and to evaluate its role as a predictive marker in
      response to therapy with Remicade. MATERIAL AND METHODS: A total of 10 patients
      with newly diagnosed sarcoidosis were enrolled together with 10 control patients
      affected by rheumatoid arthritis. All patients were studied by planar imaging of
      the chest with   (99m)Tc-infliximab at 6 h and 24 h and total body [(18)F]-FDG
      PET/CT. Regions of interest were drawn over the lungs and the right arm and
      target-to-background ratios were analysed for   (99m)Tc-infliximab. SUV mean and
      SUV max were calculated over lungs for FDG. RESULTS AND DISCUSSION: Image
      analysis showed low correlation between T/B ratios and BAL results in patients
      despite positivity at [(18)F]-FDG PET. CONCLUSION: In conclusion, patients with
      newly diagnosed pulmonary sarcoidosis, with FDG-PET and BAL positivity, showed a
      negative   (99m)Tc-infliximab scintigraphy.

PMID- 25866777
TI  - The global ecology and epidemiology of West Nile virus.
AB  - Since its initial isolation in Uganda in 1937 through the present, West Nile
      virus (WNV) has become an important cause of human and animal disease worldwide.
      WNV, an enveloped virus of the genus Flavivirus, is naturally maintained in an
      enzootic cycle between birds and mosquitoes, with occasional epizootic spillover
      causing disease in humans and horses. The mosquito vectors for WNV are widely
      distributed worldwide, and the known geographic range of WNV transmission and
      disease has continued to increase over the past 77 years. While most human
      infections with WNV are asymptomatic, severe neurological disease may develop
      resulting in long-term sequelae or death. Surveillance and preventive measures
      are an ongoing need to reduce the public health impact of WNV in areas with the
      potential for transmission. 

PMID- 25866782
TI  - Single whole-body cryostimulation procedure versus single dry sauna bath:
      comparison of oxidative impact on healthy male volunteers.
AB  - Exposure to extreme heat and cold is one of the environmental factors whose
      action is precisely based on the mechanisms involving free radicals. Fluctuations
      in ambient temperature are among the agents that toughen the human organism. The
      goal of the study was to evaluate the impact of extremely high (dry sauna, DS)
      and low (whole-body cryostimulation, WBC) environmental temperatures on the
      oxidant-antioxidant equilibrium in the blood of healthy male subjects. The
      subjects performed a single DS bath (n = 10; 26.2 +/- 4.6 years) and a single WBC
      procedure (n = 15; 27.5 +/- 3.1 years). In the subjects' blood taken immediately
      before and 20 min after the interventions, the activity of superoxide dismutase
      (SOD), catalase (CAT), and glutathione peroxidase (GPx) and the concentration of
      thiobarbituric acid reactive substances in erythrocytes (TBARSer) and blood
      plasma (TBARSpl) were determined. Single WBC and DS procedures induced an
      increase in the activity of SOD and GPx, as well as SOD and CAT, respectively.
      The SOD activity was higher after WBC than after DS. Extremely high and low
      temperatures probably induce the formation of reactive oxygen species in the
      organisms of healthy men and, therefore, disturb the oxidant-antioxidant balance.

PMID- 25866781
TI  - Involvement of the gut chemosensory system in the regulation of colonic anion
      secretion.
AB  - The primary function of the gastrointestinal (GI) tract is the extraction of
      nutrients from the diet. Therefore, the GI tract must possess an efficient
      surveillance system that continuously monitors the luminal content for beneficial
      or harmful compounds. Recent studies have shown that specialized cells in the
      intestinal lining can sense changes in this content. These changes directly
      influence fundamental GI processes such as secretion, motility, and local blood
      flow via hormonal and/or neuronal pathways. Until recently, most studies
      examining the control of ion transport in the colon have focused on neural and
      hormonal regulation. However, study of the regulation of gut function by the gut
      chemosensory system has become increasingly important, as failure of this system
      causes dysfunctions in host homeostasis, as well as functional GI disorders.
      Furthermore, regulation of ion transport in the colon is critical for host
      defense and for electrolytes balance. This review discusses the role of the gut
      chemosensory system in epithelial transport, with a particular emphasis on the
      colon. 

PMID- 25866783
TI  - Proteolytic disassembly of viral outer capsid proteins is crucial for reovirus
      mediated type-I interferon induction in both reovirus-susceptible and reovirus
      refractory tumor cells.
AB  - Oncolytic reovirus induces innate immune responses, which contribute to the
      antitumor activity of reovirus, following in vivo application. Reovirus-induced
      innate immune responses have been relatively well characterized in immune cells
      and mouse embryonic fibroblasts cells; however, the mechanisms and profiles of
      reovirus-induced innate immune responses in human tumor cells have not been well
      understood. In particular, differences in reovirus-induced innate immune
      responses between reovirus-susceptible and reovirus-refractory tumor cells remain
      unknown, although the intracellular trafficking of reovirus differs between these
      tumor cells. In this study, we examined reovirus-induced upregulation of
      interferon- (IFN-) beta and of the proapoptotic gene, Noxa, in reovirus
      susceptible and -refractory tumor cells. IFN-beta and Noxa were significantly
      induced by reovirus via the IFN-beta promoter stimulator-1 (IPS-1) signaling in
      both types of tumor cells. Inhibition of cathepsins B and L, which are important
      for disassembly of reovirus outer capsid proteins and escape into cytoplasm,
      largely suppressed reovirus-induced upregulation of IFN-beta and Noxa expression
      in not only reovirus-susceptible but also reovirus-refractory tumor cells. These
      results indicated that in both reovirus-susceptible and reovirus-refractory tumor
      cells, disassembly of the outer capsid proteins by cathepsins and the escape into
      the cytoplasm were crucial steps for reovirus-induced innate immunity. 

PMID- 25866785
TI  - The role of autophagy in liver diseases: mechanisms and potential therapeutic
      targets.

PMID- 25866784
TI  - Influence of intra-articular administration of trichostatin a on autologous
      osteochondral transplantation in a rabbit model.
AB  - Autologous osteochondral transplantation (AOT) is a method for articular
      cartilage repair. However, several disadvantages of this method have been
      reported, such as transplanted cartilage degeneration and the lack of a
      connection between the grafted and adjacent cartilage tissues. To evaluate the
      effect of intra-articular administration of trichostatin A (TSA) on AOT, we
      conducted a case control study in a rabbit model. International Cartilage Repair
      Society (ICRS) macroscopic scores, the modified O'Driscoll histology scores, and
      real-time PCR were utilized to evaluate the results. At 4 weeks, both macroscopic
      and histological assessments showed that there was no significant difference
      between the TSA and control groups. However, the mean macroscopic and
      histological scores for the TSA-treated group were significantly higher than the
      scores for the control group at 12 weeks. TSA was shown to directly reduce
      collagen type II (COL2), aggrecan, matrix metalloproteinase (MMP), and a
      disintegrin and metalloproteinase domain with thrombospondin motifs 5 (ADAMTS-5)
      expression and to simultaneously repress the upregulation of MMP-3, MMP-9, and
      MMP-13 levels induced by interleukin 1beta (IL-1beta) in chondrocytes. In
      conclusion, TSA protects AOT grafts from degeneration, which may provide a
      benefit in the repair of articular cartilage injury. 

PMID- 25866786
TI  - Ouabain-induced cytoplasmic vesicles and their role in cell volume maintenance.
AB  - Cellular swelling is controlled by an active mechanism of cell volume regulation
      driven by a Na(+)/K(+)-dependent ATPase and by aquaporins which translocate water
      along the osmotic gradient. Na(+)/K(+)-pump may be blocked by ouabain, a
      digitalic derivative, by inhibition of ATP, or by drastic ion alterations of
      extracellular fluid. However, it has been observed that some tissues are still
      able to control their volume despite the presence of ouabain, suggesting the
      existence of other mechanisms of cell volume control. In 1977, by correlating
      electron microscopy observation with ion and water composition of liver slices
      incubated in different metabolic conditions in the presence or absence of
      ouabain, we observed that hepatocytes were able to control their volume extruding
      water and recovering ion composition in the presence of ouabain. In particular,
      hepatocytes were able to sequester ions and water in intracellular vesicles and
      then secrete them at the bile canaliculus pole. We named this "vesicular
      mechanism of cell volume control." Afterward, this mechanism has been confirmed
      by us and other laboratories in several mammalian tissues. This review summarizes
      evidences regarding this mechanism, problems that are still pending, and
      questions that need to be answered. Finally, we shortly review the importance of
      cell volume control in some human pathological conditions. 

PMID- 25866787
TI  - Improvement of biogas production from orange peel waste by leaching of limonene.
AB  - Limonene is present in orange peel wastes and is known as an antimicrobial agent,
      which impedes biogas production when digesting the peels. In this work,
      pretreatment of the peels to remove limonene under mild condition was proposed by
      leaching of limonene using hexane as solvent. The pretreatments were carried out
      with homogenized or chopped orange peel at 20-40 degrees C with orange peel waste
      and hexane ratio (w/v) ranging from 1 : 2 to 1 : 12 for 10 to 300 min. The
      pretreated peels were then digested in batch reactors for 33 days. The highest
      biogas production was achieved by treating chopped orange peel waste and hexane
      ratio of 12 : 1 at 20 degrees C for 10 min corresponding to more than threefold
      increase of biogas production from 0.061 to 0.217 m(3) methane/kg VS. The solvent
      recovery was 90% using vacuum filtration and needs further separation using
      evaporation. The hexane residue in the peel had a negative impact on biogas
      production as shown by 28.6% reduction of methane and lower methane production of
      pretreated orange peel waste in semicontinuous digestion system compared to that
      of untreated peel.

PMID- 25866788
TI  - MicroRNAs: emerging novel targets of cancer therapies.

PMID- 25866789
TI  - Genetic and technological characterisation of vineyard- and winery-associated
      lactic acid bacteria.
AB  - Vineyard- and winery-associated lactic acid bacteria (LAB) from two major PDO
      regions in Greece, Peza and Nemea, were surveyed. LAB were isolated from grapes,
      fermenting musts, and winery tanks performing spontaneous malolactic
      fermentations (MLF). Higher population density and species richness were detected
      in Nemea than in Peza vineyards and on grapes than in fermenting musts.
      Pediococcus pentosaceus and Lactobacillus graminis were the most abundant LAB on
      grapes, while Lactobacillus plantarum dominated in fermenting musts from both
      regions. No particular structure of Lactobacillus plantarum populations according
      to the region of origin was observed, and strain distribution seems random. LAB
      species diversity in winery tanks differed significantly from that in vineyard
      samples, consisting principally of Oenococcus oeni. Different strains were
      analysed as per their enological characteristics and the ability to produce
      biogenic amines (BAs). Winery-associated species showed higher resistance to low
      pH, ethanol, SO2, and CuSO4 than vineyard-associated isolates. The frequency of
      BA-producing strains was relatively low but not negligible, considering that
      certain winery-associated Lactobacillus hilgardii strains were able to produce
      BAs. Present results show the necessity of controlling the MLF by selected
      starters in order to avoid BA accumulation in wine. 

PMID- 25866790
TI  - Inactivation of Src-to-ezrin pathway: a possible mechanism in the ouabain
      mediated inhibition of A549 cell migration.
AB  - Ouabain, a cardiac glycoside found in plants, is primarily used in the treatment
      of congestive heart failure and arrhythmia because of its ability to inhibit
      Na(+)/K(+)-ATPase pump. Recently ouabain has been shown to exert anticancer
      effects but the underlying mechanism is not clear. Here, we explored the
      molecular mechanism by which ouabain exerts anticancer effects in human lung
      adenocarcinoma. Employing proteomic techniques, we found 7 proteins downregulated
      by ouabain in A549 including p-ezrin, a protein associated with pulmonary cancer
      metastasis in a dose-dependent manner. In addition, when the relative
      phosphorylation levels of 39 intracellular proteins were compared between control
      and ouabain-treated A549 cells, p-Src (Y416) was also found to be downregulated
      by ouabain. Furthermore, western blot revealed the ouabain-mediated
      downregulation of p-FAK (Y925), p-paxillin (Y118), p130CAS, and Na(+)/K(+)-ATPase
      subunits that have been shown to be involved in the migration of cancer cells.
      The inhibitory effect of ouabain and Src inhibitor PP2 on the migration of A549
      cells was confirmed by Boyden chamber assay. Anticancer effects of ouabain in
      A549 cells appear to be related to its ability to regulate and inactivate Src-to
      ezrin signaling, and proteins involved in focal adhesion such as Src, FAK, and
      p130CAS axis are proposed here. 

PMID- 25866792
TI  - Modelling the longevity of dental restorations by means of a CBR system.
AB  - The lifespan of dental restorations is limited. Longevity depends on the material
      used and the different characteristics of the dental piece. However, it is not
      always the case that the best and longest lasting material is used since patients
      may prefer different treatments according to how noticeable the material is. Over
      the last 100 years, the most commonly used material has been silver amalgam,
      which, while very durable, is somewhat aesthetically displeasing. Our study is
      based on the collection of data from the charts, notes, and radiographic
      information of restorative treatments performed by Dr. Vera in 1993, the analysis
      of the information by computer artificial intelligence to determine the most
      appropriate restoration, and the monitoring of the evolution of the dental
      restoration. The data will be treated confidentially according to the Organic Law
      15/1999 on 13 December on the Protection of Personal Data. This paper also
      presents a clustering technique capable of identifying the most significant cases
      with which to instantiate the case-base. In order to classify the cases, a
      mixture of experts is used which incorporates a Bayesian network and a multilayer
      perceptron; the combination of both classifiers is performed with a neural
      network. 

PMID- 25866793
TI  - Recent advances in the use of metformin: can treating diabetes prevent breast
      cancer?
AB  - There is substantial epidemiological evidence pointing to an increased incidence
      of breast cancer and morbidity in obese, prediabetic, and diabetic patients. In
      vitro studies strongly support metformin, a diabetic medication, in breast cancer
      therapy. Although metformin has been heralded as an exciting new breast cancer
      treatment, the principal consideration is whether metformin can be used as a
      generic treatment for all breast cancer types. Importantly, will metformin be
      useful as an inexpensive therapy for patients with comorbidity of diabetes and
      breast cancer? In general, meta-analyses of clinical trial data from
      retrospective studies in which metformin treatment has been used for patients
      with diabetes and breast cancer have a positive trend; nevertheless, the
      supporting clinical data outcomes remain inconclusive. The heterogeneity of
      breast cancer, confounded by comorbidity of disease in the elderly population,
      makes it difficult to determine the actual benefits of metformin therapy. Despite
      the questionable evidence available from observational clinical studies and meta
      analyses, randomized phases I-III clinical trials are ongoing to test the
      efficacy of metformin for breast cancer. This special issue review will focus on
      recent research, highlighting in vitro research and retrospective observational
      clinical studies and current clinical trials on metformin action in breast
      cancer. 

PMID- 25866791
TI  - Insulin-like growth factor system in cancer: novel targeted therapies.
AB  - Insulin-like growth factors (IGFs) are essential for growth and survival that
      suppress apoptosis and promote cell cycle progression, angiogenesis, and
      metastatic activities in various cancers. The IGFs actions are mediated through
      the IGF-1 receptor that is involved in cell transformation induced by tumour.
      These effects depend on the bioavailability of IGFs, which is regulated by IGF
      binding proteins (IGFBPs). We describe here the role of the IGF system in cancer,
      proposing new strategies targeting this system. We have attempted to expand the
      general viewpoint on IGF-1R, its inhibitors, potential limitations of IGF-1R,
      antibodies and tyrosine kinase inhibitors, and IGFBP actions. This review
      discusses the emerging view that blocking IGF via IGFBP is a better option than
      blocking IGF receptors. This can lead to the development of novel cancer
      therapies. 

PMID- 25866794
TI  - Lipid mediators are critical in resolving inflammation: a review of the emerging
      roles of eicosanoids in diabetes mellitus.
AB  - The biosynthesis pathway of eicosanoids derived from arachidonic acid, such as
      prostaglandins and leukotrienes, relates to the pathophysiology of diabetes
      mellitus (DM). A better understanding of how lipid mediators modulate the
      inflammatory process may help recognize key factors underlying the progression of
      diabetes complications. Our review presents recent knowledge about eicosanoid
      synthesis and signaling in DM-related complications, and discusses eicosanoid
      related target therapeutics. 

PMID- 25866795
TI  - PMMA third-body wear after unicondylar knee arthroplasty decuples the UHMWPE wear
      particle generation in vitro.
AB  - INTRODUCTION: Overlooked polymethylmethacrylate after unicondylar knee
      arthroplasty can be a potential problem, since this might influence the generated
      wear particle size and morphology. The aim of this study was the analysis of
      polyethylene wear in a knee wear simulator for changes in size, morphology, and
      particle number after the addition of third-bodies. MATERIAL AND METHODS: Fixed
      bearing unicondylar knee prostheses (UKA) were tested in a knee simulator for 5.0
      million cycles. Following bone particles were added for 1.5 million cycles,
      followed by 1.5 million cycles with PMMA particles. A particle analysis by
      scanning electron microscopy of the lubricant after the cycles was performed.
      Size and morphology of the generated wear were characterized. Further, the number
      of particles per 1 million cycles was calculated for each group. RESULTS: The
      particles of all groups were similar in size and shape. The number of particles
      in the PMMA group showed 10-fold higher values than in the bone and control group
      (PMMA: 10.251 * 10(12); bone: 1.145 * 10(12); control: 1.804 * 10(12)).
      CONCLUSION: The addition of bone or PMMA particles in terms of a third-body wear
      results in no change of particle size and morphology. PMMA third-bodies generated
      tenfold elevated particle numbers. This could favor an early aseptic loosening.

PMID- 25866797
TI  - Gemcitabine, navelbine, and doxorubicin as treatment for patients with refractory
      or relapsed T-cell lymphoma.
AB  - T-cell lymphoma (TCL) is resistant to conventional chemotherapy. We
      retrospectively evaluated the therapeutic efficiency and toxicity of gemcitabine,
      navelbine, and doxorubicin (GND) in patients with refractory or relapsed TCL.
      From 2002 to 2012, 69 patients with refractory or relapsed TCL received GND
      treatment in our hospital. The treatment protocol comprised gemcitabine (800
      mg/m(2), group 1; 1000 mg/m(2), group 2) on days 1 and 8, navelbine (25 mg/m(2))
      on day 1, and doxorubicin (20 mg/m(2)) on day 1, repeated every 3 weeks. The
      overall response rate (ORR) was 65.2%. The median overall survival (OS) was 36
      months. The 5-year estimated OS rate was 32.4%. The GND regimen was well
      tolerated. Subgroup analysis demonstrated that the ORR and CR for group 1 were
      similar. A longer median OS was observed for group 1. Significant difference in
      grades 3-4 toxicities was observed between groups 1 and 2 (P = 0.035). Our study
      indicated that gemcitabine (800 mg/m(2)) on days 1 and 8 every 21 days was
      favorable for pretreated TCL patients.

PMID- 25866796
TI  - Comprehensive review on betulin as a potent anticancer agent.
AB  - Numerous plant-derived substances, and their derivatives, are effective
      antitumour and chemopreventive agents. Yet, there are also a plethora of tumour
      types that do not respond, or become resistant, to these natural substances. This
      requires the discovery of new active compounds. Betulin (BE) is a pentacyclic
      triterpene and secondary metabolite of plants abundantly found in the outer bark
      of the birch tree Betulaceae sp. BE displays a broad spectrum of biological and
      pharmacological properties, among which the anticancer and chemopreventive
      activity attract most of the attention. In this vein, BE and its natural and
      synthetic derivatives act specifically on cancer cells with low cytotoxicity
      towards normal cells. Although the antineoplastic mechanism of action of BE is
      not well understood yet, several interesting aspects of BE's interactions are
      coming to light. This review will summarize the anticancer and chemopreventive
      potential of BE in vitro and in vivo by carefully dissecting and comparing the
      doses and tumour lines used in previous studies, as well as focusing on
      mechanisms underlying its activity at cellular and molecular level, and discuss
      future prospects. 

PMID- 25866798
TI  - Polysulfated trehalose as a novel anticoagulant agent with dual mode of action.
AB  - Physiological hemostatic balance is a coordinated outcome of counteracting
      coagulation and fibrinolytic systems. An imbalance of procoagulant and
      anticoagulant factors may result in life threatening thromboembolism. Presently,
      anticoagulant administration is the first line of therapy for the treatment of
      these conditions and several anticoagulants have been approved, including various
      forms of heparin. However, the polyanionic nature and multispecificity of heparin
      pose several complications. Generally, the polysulfated compounds with
      antithrombotic potential are thought to have feasible synthetic procedures with
      much less bleeding, thus having favourable safety profiles. Here we report the
      synthesis of a novel compound, trehalose octasulfate and the assessment of its
      anticoagulation potential. Molecular docking of trehalose and trehalose
      octasulfate with antithrombin showed a specificity switch in binding affinity on
      sulfation, where trehalose octasulfate interacts with critical residues of AT
      that are either directly involved in heparin binding or in the conformational
      rearrangement of AT on heparin binding. An in vitro analysis of trehalose
      octasulfate demonstrated prolonged clotting time. Lead compound when
      intravenously injected in occlusion induced thrombotic rats showed remarkable
      reduction in the size and weight of the clot at a low dose. Delay in coagulation
      time was observed by analysing blood plasma isolated from rats preinjected with
      trehalose octasulfate. A decrease in Adenosine 5'-Diphosphate (ADP) induced
      platelet aggregation indicated a probable dual anticoagulant and antiplatelet
      mechanism of action. To summarize, this study presents trehalose octasulfate as a
      novel, effective, dual acting antithrombotic agent. 

PMID- 25866799
TI  - Physiological and selective attention demands during an international rally motor
      sport event.
AB  - PURPOSE: To monitor physiological and attention responses of drivers and
      codrivers during a World Rally Championship (WRC) event. METHODS: Observational
      data were collected from ten male drivers/codrivers on heart rate (HR), core body
      (T core) and skin temperature (T sk), hydration status (urine osmolality), fluid
      intake (self-report), and visual and auditory selective attention (performance
      tests). Measures were taken pre-, mid-, and postcompetition day and also during
      the precompetition reconnaissance. RESULTS: In ambient temperatures of 20.1
      degrees C (in-car peak 33.9 degrees C) mean (SD) peak HR and T core were
      significantly elevated (P < 0.05) during rally compared to reconnaissance (166
      (17) versus 111 (16) beats . min(-1) and 38.5 (0.4) versus 37.6 (0.2) degrees C,
      resp.). Values during competitive stages were substantially higher in drivers.
      High urine osmolality was indicated in some drivers within competition. Attention
      was maintained during the event but was significantly lower prerally, though with
      considerable individual variation. CONCLUSIONS: Environmental and physical
      demands during rally competition produced significant physiological responses.
      Challenges to thermoregulation, hydration status, and cognitive function need to
      be addressed to minimise potentially negative effects on performance and safety.

PMID- 25866800
TI  - Computational selection of RNA aptamer against angiopoietin-2 and experimental
      evaluation.
AB  - Angiogenesis plays a decisive role in the growth and spread of cancer and
      angiopoietin-2 (Ang2) is in the spotlight of studies for its unique role in
      modulating angiogenesis. The aim of this study was to introduce a computational
      simulation approach to screen aptamers with high binding ability for Ang2. We
      carried out computational simulations of aptamer-protein interactions by using
      ZDOCK and ZRANK functions in Discovery Studio 3.5 starting from the available
      information of aptamers generated through the systematic evolution of ligands by
      exponential enrichment (SELEX) in the literature. From the best of three aptamers
      on the basis of ZRANK scores, 189 sequences with two-point mutations were created
      and simulated with Ang2. Then, we used a surface plasmon resonance (SPR)
      biosensor to test 3 mutant sequences of high ZRANK scores along with a high and a
      low affinity binding sequence as reported in the literature. We found a selected
      RNA aptamer has a higher binding affinity and SPR response than a reported
      sequence with the highest affinity. This is the first study of in silico
      selection of aptamers against Ang2 by using the ZRANK scoring function, which
      should help to increase the efficiency of selecting aptamers with high target
      binding ability. 

PMID- 25866801
TI  - Exhaustive exercise attenuates the neurovascular coupling by blunting the pressor
      response to visual stimulation.
AB  - Neurovascular coupling (NVC) is assessed as an increase response to visual
      stimulation, and is monitored by blood flow of the posterior cerebral artery
      (PCA). To investigate whether exhaustive exercise modifies NVC, and more
      specifically, the relative contributions of vasodilatation in the downstream of
      PCA and the pressor response on NVC, we measured blood flow velocity in the PCA
      (PCAv) in 13 males using transcranial Doppler ultrasound flowmetry during a leg
      cycle exercise at 75% of maximal heart rate until exhaustion. NVC was estimated
      as the relative change in PCAv from the mean value obtained during 20-s with the
      eyes closed to the peak value obtained during 40-s of visual stimulation
      involving looking at a reversed checkerboard. Conductance index (CI) was
      calculated by dividing PCAv by mean arterial pressure (MAP) to evaluate the
      vasodilatation. At exhaustion, PCAv was significantly decreased relative to
      baseline measurements, and the PCAv response to visual stimulation significantly
      decreased. Compared to baseline, exhaustive exercise significantly suppressed the
      increase in MAP to visual stimulation, while the CI response did not
      significantly change by the exercise. These results suggest that exhaustive
      exercise attenuates the magnitude of NVC by blunting the pressor response to
      visual stimulation. 

PMID- 25866802
TI  - Combined therapy of diabetic peripheral neuropathy with breviscapine and
      mecobalamin: a systematic review and a meta-analysis of Chinese studies.
AB  - OBJECTIVE: A meta-analysis on combined therapy of diabetic peripheral neuropathy
      (DPN) with breviscapine and mecobalamin was performed to evaluate the efficacy of
      this therapy. METHODS: Six English databases (Medline, Cochrane Library, PubMed,
      EMBASE, Web of Science, and CINAHL) and four Chinese databases (China National
      Knowledge Infrastructure, VIP Journals Database, CBM, and Wanfang database) were
      searched for studies on the clinical trials in which DPN was treated with
      breviscapine and mecobalamin, and RevMan 5.1 package was employed for analyzing
      pooled trials and publication bias. RESULTS: A total of 17 articles including
      1398 DPN patients were identified. Homogeneity was observed among different
      studies (P = 0.74). The efficacy of combined therapy with breviscapine and
      mecobalamin was significantly better than that in control group [P < 0.0001 (OR =
      5.01, 95% CI: 3.70-6.78)]. CONCLUSION: Available findings suggest that the
      therapeutic efficacy of breviscapine combining mecobalamin is superior to
      mecobalamin alone, and this strategy is required to be popularized in clinical
      practice.

PMID- 25866803
TI  - Postexercise impact of ice-cold water bath on the oxidant-antioxidant balance in
      healthy men.
AB  - The aim of the study was to determine the effect of a 5 min head-out ice-cold
      water bath on the oxidant-antioxidant balance in response to exercise. The
      crossover study included the subjects (n = 24; aged 28.7 +/- 7.3 years) who
      performed two identical stationary cycling bouts for 30 min and recovered for 10
      min at room temperature (RT = 20 degrees C; session 1) or in a pool with ice-cold
      water (ICW = 3 degrees C, 5 min immersion; session 2). The concentration of
      thiobarbituric acid reactive substances (TBARS) in blood plasma (TBARSpl) and
      erythrocytes (TBARSer) and the erythrocytic activity of superoxide dismutase
      (SOD), catalase (CAT), and glutathione peroxidase (GPx) were measured three times
      during each of the two study sessions: before the exercise (baseline) and 20 and
      40 min after the appropriate recovery session. Lower concentration of TBARSpl 40
      min after postexercise recovery in ICW was revealed as compared with that after
      recovery at RT (P < 0.05). Moreover, a statistically significant postexercise
      increase in the TBARSpl and TBARSer concentrations was found (P < 0.01 and P <
      0.05, resp.). A short-term ice-cold water bath decreases postexercise lipid
      peroxidation.

PMID- 25866804
TI  - Analysis of chromosome 17 miRNAs and their importance in medulloblastomas.
AB  - MicroRNAs (miRNAs) are small sequences of nucleotides that regulate
      posttranscriptionally gene expression. In recent years they have been recognized
      as very important general regulators of proliferation, differentiation, adhesion,
      cell death, and others. In some cases, the characteristic presence of miRNAs
      reflects some of the cellular pathways that may be altered. Particularly
      medulloblastomas (MB) represent entities that undergo almost characteristic
      alterations of chromosome 17: from loss of discrete fragments and isochromosomes
      formation to complete loss of one of them. An analysis of the major loci on this
      chromosome revealed that it contains at least 19 genes encoding miRNAs which may
      regulate the development and differentiation of the brain and cerebellum. miRNAs
      are regulators of real complex networks; they can regulate from 100 to over 300
      messengers of various proteins. In this review some miRNAs are considered to be
      important in MB studies. Some of them are miRNA-5047, miRNA-1253, miRNA-2909, and
      miRNA-634. Everyone can significantly affect the development, growth, and cell
      invasion of MB, and they have not been explored in this tumor. In this review, we
      propose some miRNAs that can affect some genes in MB, and hence the importance of
      its study. 

PMID- 25866805
TI  - The effects of cold and lower body negative pressure on cardiovascular
      homeostasis.
AB  - PURPOSE: The purpose of this study is to determine how cold exposure and lower
      body negative pressure effected cardiovascular variables. METHODS: Eleven males
      (20.3 years +/- 2.7) underwent two 20-minute exposures to LBNP. During the 2
      trials, the subjects were exposed to cold air (10 degrees C) (COLD) and to
      ambient temperature (23 degrees C) (AMB). The trials consisted of a 100-minute
      pre-LBNP period followed by a 20-minute exposure to LBNP and then a 15-minute
      recovery period. Cardiovascular variables were recorded every 30 minutes using
      bioimpedance. RESULTS: When LBNP was applied during the AMB trials, stroke volume
      immediately decreased. During the COLD trial, there was a five-minute delay
      before the decrease in stroke volume. Heart rate increased immediately after LBNP
      initiation during the AMB trials but there was a delay in the increase during the
      COLD trials. That same pattern was followed with mean arterial blood pressures.
      Cerebral oxygenation was significantly lower throughout the COLD trial as
      compared to the AMB trials. Six subjects reported symptoms of syncope or
      presyncope during the AMB trials but there were no reports of symptoms during the
      COLD trials. CONCLUSION: From analysis of this data, cold improved the subject's
      tolerance to LBNP.

PMID- 25866807
TI  - Diagnostic value of MRI proton density fat fraction for assessing liver steatosis
      in chronic viral C hepatitis.
AB  - OBJECTIVE: To assess the diagnostic performance of a T1-independent, T2*
      corrected multiecho magnetic resonance imaging (MRI) technique for the
      quantification of hepatic steatosis in a cohort of patients affected by chronic
      viral C hepatitis, using liver biopsy as gold standard. METHODS: Eighty-one
      untreated patients with chronic viral C hepatitis were prospectively enrolled.
      All included patients underwent MRI, transient elastography, and liver biopsy
      within a time interval <10 days. RESULTS: Our cohort of 77 patients included
      43/77 (55.8%) males and 34/77 (44.2%) females with a mean age of 51.31 +/- 11.27
      (18-81) years. The median MRI PDFF showed a strong correlation with the
      histological fat fraction (FF) (r = 0.754, 95% CI 0.637 to 0.836, P < 0.0001),
      and the correlation was influenced by neither the liver stiffness nor the T2*
      decay. The median MRI PDFF result was significantly lower in the F4 subgroup (P <
      0.05). The diagnostic accuracy of MRI PDFF evaluated by AUC-ROC analysis was
      0.926 (95% CI 0.843 to 0.973) for S >= 1 and 0.929 (95% CI 0.847 to 0.975) for S
      = 2. CONCLUSIONS: Our MRI technique of PDFF estimation allowed discriminating
      with a good diagnostic accuracy between different grades of hepatic steatosis.

PMID- 25866806
TI  - Placing ion channels into a signaling network of T cells: from maturing
      thymocytes to healthy T lymphocytes or leukemic T lymphoblasts.
AB  - T leukemogenesis is a multistep process, where the genetic errors during T cell
      maturation cause the healthy progenitor to convert into the leukemic precursor
      that lost its ability to differentiate but possesses high potential for
      proliferation, self-renewal, and migration. A new misdirecting "leukemogenic"
      signaling network appears, composed by three types of participants which are
      encoded by (1) genes implicated in determined stages of T cell development but
      deregulated by translocations or mutations, (2) genes which normally do not
      participate in T cell development but are upregulated, and (3) nondifferentially
      expressed genes which become highly interconnected with genes expressed
      differentially. It appears that each of three groups may contain genes coding ion
      channels. In T cells, ion channels are implicated in regulation of cell cycle
      progression, differentiation, activation, migration, and cell death. In the
      present review we are going to reveal a relationship between different genetic
      defects, which drive the T cell neoplasias, with calcium signaling and ion
      channels. We suggest that changes in regulation of various ion channels in
      different types of the T leukemias may provide the intracellular ion
      microenvironment favorable to maintain self-renewal capacity, arrest
      differentiation, induce proliferation, and enhance motility. 

PMID- 25866808
TI  - The formation of biofilms by Pseudomonas aeruginosa: a review of the natural and
      synthetic compounds interfering with control mechanisms.
AB  - P. aeruginosa is an opportunistic pathogenic bacterium responsible for both acute
      and chronic infections. Beyond its natural resistance to many drugs, its ability
      to form biofilm, a complex biological system, renders ineffective the clearance
      by immune defense systems and antibiotherapy. The objective of this report is to
      provide an overview (i) on P. aeruginosa biofilm lifestyle cycle, (ii) on the
      main key actors relevant in the regulation of biofilm formation by P. aeruginosa
      including QS systems, GacS/GacA and RetS/LadS two-component systems and C-di-GMP
      dependent polysaccharides biosynthesis, and (iii) finally on reported natural and
      synthetic products that interfere with control mechanisms of biofilm formation by
      P. aeruginosa without affecting directly bacterial viability. Concluding remarks
      focus on perspectives to consider biofilm lifestyle as a target for eradication
      of resistant infections caused by P. aeruginosa. 

PMID- 25866810
TI  - The place of extensive surgery in locoregional recurrence and limited metastatic
      disease of breast cancer: preliminary results.
AB  - The aims of this study were first to clearly define two different entities:
      locoregional recurrences and limited metastatic disease and secondly to evaluate
      the place of extensive surgery in these two types of recurrence. MATERIAL AND
      METHODS: Twenty-four patients were followed from June 2004 until May 2014. All
      patients underwent surgery but for 1 patient this surgery was stopped because the
      tumour was unresectable. RESULTS: The median interval between surgery for the
      primary tumour and the locoregional recurrence or metastatic evolution was 129
      months. Eight patients had pure nodal recurrences, 4 had nodal and muscular
      recurrences, 5 had muscular + skin recurrences, and 8 had metastatic evolution.
      Currently, all patients are still alive but 2 have liver metastases. Disease free
      survival was measured at 2 years and extrapolated at 5 years and was 92% at these
      two time points. No difference was observed for young or older women; limited
      metastatic evolution and locoregional recurrence exhibited the same disease free
      survival. CONCLUSION: Extensive surgery has a place in locoregional and limited
      metastatic breast cancer recurrences but this option must absolutely be
      integrated in the multidisciplinary strategy of therapeutic options and needs to
      be planned with a curative intent.

PMID- 25866812
TI  - Nutrients and muscle disease.

PMID- 25866811
TI  - A phase I trial to evaluate the multiple-dose safety and antitumor activity of
      ursolic acid liposomes in subjects with advanced solid tumors.
AB  - Ursolic acid liposome (UAL), a new antitumor drug, has potential therapeutic
      value. However, limited clinical data exists regarding multiple-dose safety,
      antitumor activity, and the recommended dose (RD) of UAL for subjects with
      advanced solid tumors. All subjects were intravenously administered UAL for 14
      consecutive days of a 21-day treatment cycle. Twenty-one subjects were enrolled
      in 1 of 3 sequential cohorts (56, 74, and 98 mg/m(2)) to evaluate multiple-dose
      tolerability and efficacy. Eight additional subjects were treated with UAL (74
      mg/m(2)) to evaluate multiple-dose pharmacokinetics. No >=grade 3 adverse events
      (NCI-CTC) were observed. Sixty percent subjects achieved stable disease after 2
      treatment cycles. Multiple-dose pharmacokinetic analysis suggested UAL does not
      accumulate in the body. This trial demonstrates that UAL was tolerable, had
      manageable toxicity, and could potentially improve patient remission rates. A
      large phase II study is recommended to confirm these results (i.e., RD of 98
      mg/m(2)). 

PMID- 25866809
TI  - Physiological impact of abnormal lipoxin A4 production on cystic fibrosis airway
      epithelium and therapeutic potential.
AB  - Lipoxin A4 has been described as a major signal for the resolution of
      inflammation and is abnormally produced in the lungs of patients with cystic
      fibrosis (CF). In CF, the loss of chloride transport caused by the mutation in
      the cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel gene
      results in dehydration, mucus plugging, and reduction of the airway surface
      liquid layer (ASL) height which favour chronic lung infection and neutrophil
      based inflammation leading to progressive lung destruction and early death of
      people with CF. This review highlights the unique ability of LXA4 to restore
      airway surface hydration, to stimulate airway epithelial repair, and to
      antagonise the proinflammatory program of the CF airway, circumventing some of
      the most difficult aspects of CF pathophysiology. The report points out novel
      aspects of the cellular mechanism involved in the physiological response to LXA4,
      including release of ATP from airway epithelial cell via pannexin channel and
      subsequent activation of and P2Y11 purinoreceptor. Therefore, inadequate
      endogenous LXA4 biosynthesis reported in CF exacerbates the ion transport
      abnormality and defective mucociliary clearance, in addition to impairing the
      resolution of inflammation, thus amplifying the vicious circle of airway
      dehydration, chronic infection, and inflammation. 

PMID- 25866813
TI  - Trichostatin A-mediated epigenetic transformation of adult bone marrow-derived
      mesenchymal stem cells biases the in vitro developmental capability, quality, and
      pluripotency extent of porcine cloned embryos.
AB  - The current research was conducted to explore the in vitro developmental outcome
      and cytological/molecular quality of porcine nuclear-transferred (NT) embryos
      reconstituted with adult bone marrow-derived mesenchymal stem cells (ABM-MSCs)
      that were epigenetically transformed by treatment with nonspecific inhibitor of
      histone deacetylases, known as trichostatin A (TSA). The cytological quality of
      cloned blastocysts was assessed by estimation of the total cells number (TCN) and
      apoptotic index. Their molecular quality was evaluated by real-time PCR-mediated
      quantification of gene transcripts for pluripotency- and multipotent stemness
      related markers (Oct4, Nanog, and Nestin). The morula and blastocyst formation
      rates of NT embryos derived from ABM-MSCs undergoing TSA treatment were
      significantly higher than in the TSA-unexposed group. Moreover, the NT
      blastocysts generated using TSA-treated ABM-MSCs exhibited significantly higher
      TCN and increased pluripotency extent measured with relative abundance of Oct4
      and Nanog mRNAs as compared to the TSA-untreated group. Altogether, the
      improvements in morula/blastocyst yields and quality of cloned pig embryos seem
      to arise from enhanced abilities for promotion of correct epigenetic
      reprogramming of TSA-exposed ABM-MSC nuclei in a cytoplasm of reconstructed
      oocytes. To our knowledge, we are the first to report the successful production
      of mammalian high-quality NT blastocysts using TSA-dependent epigenomic
      modulation of ABM-MSCs. 

PMID- 25866815
TI  - Multifaceted roles of cysteinyl leukotrienes in eliciting eosinophil granule
      protein secretion.
AB  - Cysteinyl leukotrienes (cysLTs) are cell membrane-impermeant lipid mediators that
      play major roles in the pathogenesis of eosinophilic inflammation and are
      recognized to act via at least 2 receptors, namely, cysLT1 receptor (cysLT1R) and
      cysLT2 receptor (cysLT2R). Eosinophils, which are granulocytes classically
      associated with host defense against parasitic helminthes and allergic
      conditions, are distinguished from leukocytes by their dominant population of
      cytoplasmic crystalloid (also termed secretory, specific, or secondary) granules
      that contain robust stores of diverse preformed proteins. Human eosinophils are
      the main source of cysLTs and are recognized to express both cysLTs receptors
      (cysLTRs) on their surface, at the plasma membrane. More recently, we identified
      the expression of cysLTRs in eosinophil granule membranes and demonstrated that
      cysLTs, acting via their granule membrane-expressed receptors, elicit secretion
      from cell-free human eosinophil granules. Herein, we review the multifaceted
      roles of cysLTs in eliciting eosinophil granule protein secretion. We discuss the
      intracrine and autocrine/paracrine secretory responses evoked by cysLTs in
      eosinophils and in cell-free extracellular eosinophil crystalloid granules. We
      also discuss the importance of this finding in eosinophil immunobiology and
      speculate on its potential role(s) in eosinophilic diseases. 

PMID- 25866814
TI  - Chemotherapy and chemoprevention by thiazolidinediones.
AB  - Thiazolidinediones (TZDs) are synthetic ligands of Peroxisome-Proliferator
      Activated Receptor gamma (PPARgamma). Troglitazone, rosiglitazone, and
      pioglitazone have been approved for treatment of diabetes mellitus type II. All
      three compounds, together with the first TZD ciglitazone, also showed an
      antitumor effect in preclinical studies and a beneficial effect in some clinical
      trials. This review summarizes hypotheses on the role of PPARgamma in tumors, on
      cellular targets of TZDs, antitumor effects of monotherapy and of TZDs in
      combination with other compounds, with a focus on their role in the treatment of
      differentiated thyroid carcinoma. The results of chemopreventive effects of TZDs
      are also considered. Existing data suggest that the action of TZDs is highly
      complex and that actions do not correlate with cellular PPARgamma expression
      status. Effects are cell-, species-, and compound-specific and concentration
      dependent. Data from human trials suggest the efficacy of TZDs as monotherapy in
      prostate cancer and glioma and as chemopreventive agent in colon, lung, and
      breast cancer. TZDs in combination with other therapies might increase antitumor
      effects in thyroid cancer, soft tissue sarcoma, and melanoma. 

PMID- 25866817
TI  - Diabetic retinopathy: mechanism, diagnosis, prevention, and treatment.

PMID- 25866816
TI  - Updates and knowledge gaps in cholesteatoma research.
AB  - The existence of acquired cholesteatoma has been recognized for more than three
      centuries; however, the nature of the disorder has yet to be determined. Without
      timely detection and intervention, cholesteatomas can become dangerously large
      and invade intratemporal structures, resulting in numerous intra- and
      extracranial complications. Due to its aggressive growth, invasive nature, and
      the potentially fatal consequences of intracranial complications, acquired
      cholesteatoma remains a cause of morbidity and death for those who lack access to
      advanced medical care. Currently, no viable nonsurgical therapies are available.
      Developing an effective management strategy for this disorder will require a
      comprehensive understanding of past progress and recent advances. This paper
      presents a brief review of background issues related to acquired middle ear
      cholesteatoma and deals with practical considerations regarding the history and
      etymology of the disorder. We also consider issues related to the classification,
      epidemiology, histopathology, clinical presentation, and complications of
      acquired cholesteatoma and examine current diagnosis and management strategies in
      detail. 

PMID- 25866818
TI  - The effects of metabolic work rate and ambient environment on physiological
      tolerance times while wearing explosive and chemical personal protective
      equipment.
AB  - This study evaluated the physiological tolerance times when wearing explosive and
      chemical (>35 kg) personal protective equipment (PPE) in simulated environmental
      extremes across a range of differing work intensities. Twelve healthy males
      undertook nine trials which involved walking on a treadmill at 2.5, 4, and 5.5
      km.h(-1) in the following environmental conditions, 21, 30, and 37 degrees C wet
      bulb globe temperature (WBGT). Participants exercised for 60 min or until
      volitional fatigue, core temperature reached 39 degrees C, or heart rate exceeded
      90% of maximum. Tolerance time, core temperature, skin temperature, mean body
      temperature, heart rate, and body mass loss were measured. Exercise time was
      reduced in the higher WBGT environments (WBGT37 < WBGT30 < WBGT21; P < 0.05) and
      work intensities (5.5 < 4 < 2.5 km.h(-1); P < 0.001). The majority of trials
      (85/108; 78.7%) were terminated due to participant's heart rate exceeding 90% of
      their maximum. A total of eight trials (7.4%) lasted the full duration. Only nine
      (8.3%) trials were terminated due to volitional fatigue and six (5.6%) due to
      core temperatures in excess of 39 degrees C. These results demonstrate that
      physiological tolerance times are influenced by the external environment and
      workload and that cardiovascular strain is the limiting factor to work tolerance
      when wearing this heavy multilayered PPE. 

PMID- 25866819
TI  - Diffusion-weighted MRI for the assessment of liver fibrosis: principles and
      applications.
AB  - The importance of an early identification of hepatic fibrosis has been
      emphasized, in order to start therapy and obtain fibrosis regression. Biopsy is
      the gold-standard method for the assessment of liver fibrosis in chronic liver
      diseases, but it is limited by complications, interobserver variability, and
      sampling errors. Several noninvasive methods have been recently introduced into
      clinical routine, in order to detect liver fibrosis early. One of the most
      diffuse approaches is represented by diffusion-weighted liver MRI. In this
      review, the main technical principles are briefly reported in order to explain
      the rationale for clinical applications. In addition, roles of apparent diffusion
      coefficient, intravoxel incoherent motion, and relative apparent diffusion
      coefficient are also reported, showing their advantages and limits. 

PMID- 25866820
TI  - A new methodology for evaluation of nematode viability.
AB  - Nematodes infections are responsible for debilitating conditions and economic
      losses in domestic animals as well as livestock and are considered an important
      public health problem due to the high prevalence in humans. The nematode
      resistance for drugs has been reported for livestock, highlighting the importance
      for development of new anthelmintic compounds. The aim of the current study was
      to apply and compare fluorimetric techniques using Sytox and propidium iodide for
      evaluating the viability of C. elegans larvae after treatment with anthelmintic
      drugs. These fluorescent markers were efficient to stain larvae treated with
      ivermectin and albendazole sulfoxide. We observed that densitometric values were
      proportional to the concentration of dead larvae stained with both markers.
      Furthermore, data on motility test presented an inverse correlation with
      fluorimetric data when ivermectin was used. Our results showed that lower
      concentrations of drugs were effective to interfere in the processes of cellular
      transport while higher drugs concentrations were necessary in order to result in
      any damage to cell integrity. The methodology described in this work might be
      useful for studies that aim to evaluate the viability of nematodes, particularly
      for testing of new anthelminthic compounds using an easy, economic, reproducible,
      and no time-consuming technique. 

PMID- 25866821
TI  - The plant growth-promoting bacteria Azospirillum amazonense: genomic versatility
      and phytohormone pathway.
AB  - The rhizosphere bacterium Azospirillum amazonense associates with plant roots to
      promote plant growth. Variation in replicon numbers and rearrangements is common
      among Azospirillum strains, and characterization of these naturally occurring
      differences can improve our understanding of genome evolution. We performed an in
      silico comparative genomic analysis to understand the genomic plasticity of A.
      amazonense. The number of A. amazonense-specific coding sequences was similar
      when compared with the six closely related bacteria regarding belonging or not to
      the Azospirillum genus. Our results suggest that the versatile gene repertoire
      found in A. amazonense genome could have been acquired from distantly related
      bacteria from horizontal transfer. Furthermore, the identification of coding
      sequence related to phytohormone production, such as flavin-monooxygenase and
      aldehyde oxidase, is likely to represent the tryptophan-dependent TAM pathway for
      auxin production in this bacterium. Moreover, the presence of the coding sequence
      for nitrilase indicates the presence of the alternative route that uses IAN as an
      intermediate for auxin synthesis, but it remains to be established whether the
      IAN pathway is the Trp-independent route. Future investigations are necessary to
      support the hypothesis that its genomic structure has evolved to meet the
      requirement for adaptation to the rhizosphere and interaction with host plants. 

PMID- 25866822
TI  - Patients with intolerance reactions to total knee replacement: combined
      assessment of allergy diagnostics, periprosthetic histology, and peri-implant
      cytokine expression pattern.
AB  - We performed a combined approach to identify suspected allergy to knee
      arthroplasty (TKR): patch test (PT), lymphocyte transformation test (LTT),
      histopathology (overall grading; T- and B-lymphocytes, macrophages, and
      neutrophils), and semiquantitative Real-time-PCR-based periprosthetic
      inflammatory mediator analysis (IFNgamma, TNFalpha, IL1-beta, IL-2, IL-6, IL-8,
      IL-10, IL17, and TGFbeta). We analyzed 25 TKR patients with yet unexplained
      complications like pain, effusion, and reduced range of motion. They consisted of
      20 patients with proven metal sensitization (11 with PT reactions; 9 with only
      LTT reactivity). Control specimens were from 5 complicated TKR patients without
      metal sensitization, 12 OA patients before arthroplasty, and 8 PT patients
      without arthroplasty. Lymphocytic infiltrates were seen and fibrotic (Type IV
      membrane) tissue response was most frequent in the metal sensitive patients, for
      example, in 81% of the PT positive patients. The latter also had marked
      periprosthetic IFNgamma expression. 8/9 patients with revision surgery using Ti
      coated/oxinium based implants reported symptom relief. Our findings demonstrate
      that combining allergy diagnostics with histopathology and periprosthetic
      cytokine assessment could allow us to design better diagnostic strategies. 

PMID- 25866824
TI  - Exposure to Allergen Causes Changes in NTS Neural Activities after Intratracheal
      Capsaicin Application, in Endocannabinoid Levels and in the Glia Morphology of
      NTS.
AB  - Allergen exposure may induce changes in the brainstem secondary neurons, with
      neural sensitization of the nucleus solitary tract (NTS), which in turn can be
      considered one of the causes of the airway hyperresponsiveness, a characteristic
      feature of asthma. We evaluated neurofunctional, morphological, and biochemical
      changes in the NTS of naive or sensitized rats. To evaluate the cell firing
      activity of NTS, in vivo electrophysiological experiments were performed before
      and after capsaicin challenge in sensitized or naive rats. Immunohistochemical
      studies, endocannabinoid, and palmitoylethanolamide quantification in the NTS
      were also performed. This study provides evidence that allergen sensitization in
      the NTS induced: (1) increase in the neural firing response to intratracheal
      capsaicin application, (2) increase of endocannabinoid anandamide and
      palmitoylethanolamide, a reduction of 2-arachidonoylglycerol levels in the NTS,
      (3) glial cell activation, and (4) prevention by a Group III metabotropic
      glutamate receptor activation of neural firing response to intratracheal
      application of capsaicin in both naive and sensitized rats. Therefore,
      normalization of ovalbumin-induced NTS neural sensitization could open up the
      prospect of new treatments based on the recovery of specific brain nuclei
      function and for extensive studies on acute or long-term efficacy of selective
      mGlu ligand, in models of bronchial hyperreactivity. 

PMID- 25866825
TI  - Evaluating the effect of Sarconesiopsis magellanica (Diptera: Calliphoridae)
      larvae-derived haemolymph and fat body extracts on chronic wounds in diabetic
      rabbits.
AB  - We evaluated extracts taken from S. magellanica third instar larvae fat body and
      haemolymph using a diabetic rabbit model and compared this to the effect obtained
      with the same substances taken from Lucilia sericata larvae. Alloxan (a toxic
      glucose analogue) was used to induce experimental diabetes in twelve rabbits.
      Dorsal wounds were made in each animal and they were infected with Staphylococcus
      aureus and Pseudomonas aeruginosa. They were then treated with haemolymph and
      lyophilized extracts taken from the selected blowflies' larvae fat bodies. Each
      wound was then evaluated by using rating scales and histological analysis. More
      favourable scores were recorded on the PUSH and WBS scales for the wounds treated
      with fat body derived from the larvae of both species compared to that obtained
      with haemolymph; however, wounds treated with the substances taken from S.
      magellanica had better evolution. Histological analysis revealed that treatment
      led to tissue proliferation and more effective neovascularisation in less time
      with both species' fat body extracts compared to treatment with just haemolymph.
      The results suggest the effectiveness of the substances evaluated and validate
      them in the animal model being used here as topical agents in treating chronic
      wounds. 

PMID- 25866823
TI  - The association between type 2 diabetes mellitus and women cancer: the
      epidemiological evidences and putative mechanisms.
AB  - Type 2 diabetes mellitus (T2DM), a chronic disease increasing rapidly worldwide,
      is well established as an important risk factor for various types of cancer.
      Although many factors impact the development of T2DM and cancer including sex,
      age, ethnicity, obesity, diet, physical activity levels, and environmental
      exposure, many epidemiological and experimental studies are gradually
      contributing to knowledge regarding the interrelationship between DM and cancer.
      The insulin resistance, hyperinsulinemia, and chronic inflammation associated
      with diabetes mellitus are all associated strongly with cancer. The changes in
      bioavailable ovarian steroid hormone that occur in diabetes mellitus (the
      increasing levels of estrogen and androgen and the decreasing level of
      progesterone) are also considered potentially carcinogenic conditions for the
      breast, endometrium, and ovaries in women. In addition, the interaction among
      insulin, insulin-like growth factors (IGFs), and ovarian steroid hormones, such
      as estrogen and progesterone, could act synergistically during cancer
      development. Here, we review the cancer-related mechanisms in T2DM, the
      epidemiological evidence linking T2DM and cancers in women, and the role of
      antidiabetic medication in these cancers. 

PMID- 25866826
TI  - NADPH oxidase 4-derived H2O2 promotes aberrant retinal neovascularization via
      activation of VEGF receptor 2 pathway in oxygen-induced retinopathy.
AB  - NADPH oxidase 4 (Nox4) is a major isoform of NADPH oxidase in retinal endothelial
      cells. Our previous study suggests that upregulation of Nox4 in retinal
      endothelial cells contributes to retinal vascular leakage in diabetes. In the
      current study, we investigated the role and mechanism of Nox4 in regulation of
      retinal neovascularization (NV), a hallmark of proliferative diabetic retinopathy
      (PDR), using a mouse model of oxygen-induced retinopathy (OIR). Our results
      confirmed that Nox4 was expressed predominantly in retinal vasculature of mouse
      retina. Retinal expression of Nox4 was markedly increased in OIR, in parallel
      with enhanced phosphorylation of ERK. In human retinal microvascular endothelial
      cells (HRECs), overexpression of Nox4 by adenovirus significantly increased
      extracellular H2O2 generation, resulting in intensified VEGFR2 activation and
      exacerbated angiogenesis upon VEGF stimulation. In contrast, silencing Nox4
      expression or scavenging H2O2 by polyethylene glycol- (PEG-) conjugated catalase
      inhibited endothelial migration, tube formation, and VEGF-induced activation of
      VEGFR2 signaling. Importantly, knockdown of retinal Nox4 by adenovirus-delivered
      siRNA significantly reduced ERK activation and attenuated retinal NV formation in
      OIR. Taken together, our data indicate that Nox4 promotes retinal NV formation
      through H2O2/VEGFR2/ERK signaling pathway. Reducing retinal Nox4 expression may
      represent a promising therapeutic approach for neovascular retinal diseases such
      as PDR. 

PMID- 25866828
TI  - Growth modeling of the maternal cytokine milieu throughout normal pregnancy:
      macrophage-derived chemokine decreases as inflammation/counterregulation
      increases.
AB  - Several recent studies have shown differences in the maternal immune milieu at
      different phases of pregnancy, but most studies have been cross-sectional or of
      relatively few time points. Levels of 42 cytokines were determined using a
      multiplex bead-based assay on archived serum from a cohort of pregnant women (N =
      16) at median of 18 time points tested, from the first trimester through to
      parturition, per woman. Unconditional growth modeling was then used to determine
      time-dependent changes in levels of these cytokines. Macrophage-derived chemokine
      (MDC, aka CCL22) decreases as pregnancy progresses. IL-1beta, IL-6, IL-8, IL
      12p70, IL-13, IL-15, IP-10, and FLT3-ligand increase as a function of gestational
      weeks, and IFNalpha2, IL-1ra, IL-3, IL-9, IL-12p40, and soluble CD40 ligand
      increase as a function of trimester. As pregnancy normally progresses, a maternal
      shift away from a type 2-biased immune response and toward an
      inflammatory/counterregulatory response is observed. 

PMID- 25866829
TI  - DDDAS Design of Drug Interventions for the Treatment of Dyslipidemia in ApoE-/-
      Mice.
AB  - Computational models of complex systems, such as signaling networks and
      biological systems, can be used to explain the behavior of such systems under
      various conditions. The large number of integrated processes and variables, and
      the nonlinearities inherent in the fundamental processes, make it difficult for
      scientists unassisted by computer simulations to effectively predict the
      consequences of a particular intervention. For this reason, computer simulation
      has become an important tool for generating hypotheses about the behavior of
      these systems that can then be tested in the laboratory and clinic. A dynamic
      data-driven application simulation (DDDAS) was designed by Biospherics to model
      complex metabolic disease pathways by testing potential binary therapies in
      simulations at various combinations of two points in the pathways. Since DDDAS
      chooses the most effective pair-wise combinations, this data-driven system allows
      for the implementation of real-time data to model or predict a measurement or
      event. By incorporating data dynamically rather than statically, the predictions
      and measurements become more reliable. Dyslipidemia, a common precursor to
      atherosclerosis, can be manifested by high triglycerides, increased
      apolipoprotein (Apo) B, high levels of LDL, and low levels of HDL. SPX106 and D
      tagatose is a combination drug therapy composed of a carbohydrate (D-tagatose)
      and SPX106. D-tagatose has been studied for the treatment of diabetes for several
      years, and has the ability to lower blood insulin levels and to decrease glycogen
      formation. SPX106 is a natural substance that accelerates lipid catabolism and
      inhibits dyslipidemia. In apolipoprotein E knockout mice (ApoE-/-), this drug
      combination has been shown to significantly lower both the amount of
      atherosclerosis and blood cholesterol levels. This study used 26 male ApoE-/-
      mice (n=13 in each group, control and treated). The control group received the
      normal "Western" diet (Harlan TD88137) and the treatment group received a
      modified version in which the sucrose was replaced with D-tagatose and 1g of
      SPX106 was added for every kilogram of chow. Mice were fed the diet for 8 weeks
      and then sacrificed via cardiac puncture. Blood serum was analyzed for
      cholesterol concentration. A significant difference was observed between the
      control and treated groups for total cholesterol levels. FPLC separations were
      done on fractions from both control and treated groups. A significant difference
      between VLDL and HDL levels was found between the treated and control mice
      (p<0.05 for both). Aortas were also taken and preserved in formalin to be
      quantified for atherosclerosis. Aortic sinuses were frozen in OCT and sectioned
      using a cryostat and then quantified for atherosclerosis. Treated mice showed
      statistically significant reduction in atherosclerosis in the aortic arch
      (p<0.01), the thoracic aorta (p<0.05), and the aortic sinus (p<0.05) as well as a
      reduction of cholesterol (p<0.05).

PMID- 25866827
TI  - Effect of TACI signaling on humoral immunity and autoimmune diseases.
AB  - Transmembrane activator and calcium-modulating cyclophilin ligand interactor
      (TACI) is one of the receptors of B cell activating factor of the tumor necrosis
      factor family (BAFF) and a proliferation-inducing ligand (APRIL). TACI is a
      regulator in the immune responses. TACI inhibits B cell expansion and promotes
      the differentiation and survival of plasma cells. The mechanisms underlying these
      effects probably involve changed expressions of some crucial molecules, such as B
      lymphocyte induced maturation protein-1 (Blimp-1) and inducible T-cell
      costimulator ligand (ICOSL) in B cells and/or plasma cells. However, abnormal
      TACI signaling may relate to autoimmune disorders. Common variable immune
      deficiency (CVID) patients with heterozygous mutations in TACI alleles increase
      susceptibility to autoimmune diseases. Taci (-/-) mice and BAFF transgenic mice
      both develop signs of human SLE. These findings that indicate inappropriate
      levels of TACI signaling may disrupt immune system balance, thereby promoting the
      development of autoimmune diseases. In this review, we summarize the basic
      characteristics of the TACI ligands BAFF and APRIL, and detail the research
      findings on the role of TACI in humoral immunity. We also discuss the possible
      mechanisms underlying the susceptibility of CVID patients with TACI mutations to
      autoimmune diseases and the role of TACI in the pathogenesis of SLE. 

PMID- 25866830
TI  - Identifying targets for diagnosis, prognosis, and treatment.

PMID- 25866831
TI  - Clinical course and treatment of anti-HMGCR antibody-associated necrotizing
      autoimmune myopathy.
AB  - OBJECTIVE: We examined a cohort of Australian patients with statin exposure who
      developed a necrotizing autoimmune myopathy (NAM) associated with a novel
      autoantibody against 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and
      describe the clinical and therapeutic challenges of managing these patients and
      an optimal therapeutic strategy. METHODS: Clinical, laboratory, EMG, and
      histopathologic results and response to immunomodulation are reported in 6
      Australian patients with previous statin exposure and antibodies targeting HMGCR.
      RESULTS: All patients presented with painless proximal weakness following statin
      therapy, which persisted after statin cessation. Serum creatine kinase (CK)
      levels ranged from 2,700 to 16,200 IU/L. EMG was consistent with a myopathic
      picture. Muscle biopsies revealed a pauci-immune necrotizing myopathy. Detailed
      graphical representation of the clinical course of these patients showed a close
      association with rising CK and an increase in clinical weakness signifying
      relapses, particularly upon weaning or ceasing steroids. All 6 patients were
      responsive to initial steroid therapy, with 5 relapsing upon attempts to wean
      steroids. Both CK and clinical strength improved with the reinstitution of
      immunotherapy, in particular steroids and IV immunoglobulin (IVIg). All patients
      required treatment with varying multiagent immunosuppressive regimens to achieve
      clinical remission, including prednisone (n = 6), IVIg (n = 5), plasmapheresis (n
      = 2), and additional therapy including methotrexate (n = 6), cyclophosphamide (n
      = 2), rituximab (n = 2), azathioprine (n = 1), and cyclosporine (n = 1).
      CONCLUSIONS: Recognition of HMGCR antibody-associated NAM is important because
      these patients are responsive to immunosuppression, and early multiagent therapy
      and a slow and cautious approach to withdrawing steroids may improve outcomes.

PMID- 25866832
TI  - Glial cells express nuclear nrf2 after fumarate treatment for multiple sclerosis
      and psoriasis.

PMID- 25866833
TI  - Initiatives to Enhance Primary Care Delivery: Two Examples from the Field.
AB  - OBJECTIVES: Increasing demands on primary care providers have created a need for
      systems-level initiatives to improve primary care delivery. The purpose of this
      paper is to describe and present outcomes for two such initiatives: the
      Pennsylvania Academy of Family Physicians' Residency Program Collaborative (RPC)
      and the St. Johnsbury Vermont Community Health Team (CHT). METHODS: Researchers
      conducted case studies of the initiatives using mixed methods, including:
      secondary analysis of program and electronic health record data, systematic
      document review and interviews. RESULTS: RPC is a learning collaborative that
      teaches quality improvement and patient-centeredness to primary care providers,
      residents, clinical support staff, and administrative staff in residency
      programs. Results show that participation in a higher number of live learning
      sessions resulted in a significant increase in patient centered medical home
      recognition attainment and significant improvements in performance in diabetic
      process measures including eye exams (14.3%, p=0.004), eye referrals (13.82%,
      p=0.013), foot exams (15.73%, p=0.003), smoking cessation (15.83%, p=0.012), and
      self-management goals (25.45%, p=0.001). As a community-clinical linkages model,
      CHT involves primary care practices, community health workers (CHWs), and
      community partners. Results suggest that CHT members successfully work together
      to coordinate comprehensive care for the individuals they serve. Further,
      individuals exposed to CHWs experienced increased stability in access to health
      insurance (p=0.001) and prescription drugs (p=0.000), and the need for health
      education counseling (p=0.000). CONCLUSION: Findings from this study indicate
      that these two system-level strategies have the promise to improve primary care
      delivery. Additional research can determine the extent to which these strategies
      can improve other health outcomes.

PMID- 25866835
TI  - Respiratory Sinus Arrhythmia: A Transdiagnostic Biomarker of Emotion
      Dysregulation and Psychopathology.
AB  - In the past two decades, respiratory sinus arrhythmia (RSA)-an index of
      parasympathetic nervous system (PNS)-mediated cardiac control-has emerged as a
      reliable peripheral biomarker of emotion regulation (ER). Reduced RSA and
      excessive RSA reactivity (i.e., withdrawal) to emotional challenge are observed
      consistently among individuals with poor ER capabilities, including those with
      various forms of internalizing and externalizing psychopathology, and those with
      specific psychopathological syndromes, including anxiety, phobias, attention
      problems, autism, callousness, conduct disorder, depression, non-suicidal self
      injury, panic disorder, and trait hostility. Emerging evidence suggests that low
      RSA and excessive RSA reactivity index poor ER because they are downstream
      peripheral markers of prefrontal cortex (PFC) dysfunction. Poorly modulated
      inhibitory efferent pathways from the medial PFC to the PNS result in reduced RSA
      and excessive RSA reactivity. According to this perspective, RSA is a non
      invasive proxy for poor executive control over behavior, which characterizes most
      forms of psychopathology.

PMID- 25866836
TI  - Existence of tripled fixed points for a class of condensing operators in Banach
      spaces.
AB  - We give some results concerning the existence of tripled fixed points for a class
      of condensing operators in Banach spaces. Further, as an application, we study
      the existence of solutions for a general system of nonlinear integral equations. 

PMID- 25866834
TI  - Thyroid Hormone Signaling in Muscle Development, Repair and Metabolism.
AB  - Skeletal muscle is a plastic organ made by highly specialize fibers with specific
      and different structure, function and metabolism. Skeletal muscle fibers can
      adapt, change, recover/regenerate after injury in response to various stimulators
      including hormones. Thyroid hormones are important players in the homeostasis of
      several tissue including skeletal muscle and their genomic action mostly depend
      on the tissue T3 bioavailability and on the distribution of the thyroid receptor
      isoforms which act as transcription factors and are modulated by T3. Changing in
      contractile and metabolic proprieties of the muscle fibers has been described in
      experimental models of hyper and hypothyroidism. Animal models with disruption of
      thyroid hormone signaling showed different and specific skeletal muscle
      phenotypes. By focusing on thyroid hormone signaling in skeletal muscle
      homeostasis, we review T3 specific action on skeletal muscle development,
      postnatal growth, function and metabolism.

PMID- 25866837
TI  - First report of CTNS mutations in a Chinese family with infantile cystinosis.
AB  - Infantile cystinosis (IC) is a rare autosomal recessive disorder characterized by
      a defect in the lysosomal-membrane transport protein, cystinosin. It serves as a
      prototype for lysosomal transport disorders. To date, several CTNS mutations have
      been identified as the cause of the prototypic disease across different ethnic
      populations worldwide. However, in Asia, the CTNS mutation is very rarely
      reported. For the Chinese population, no literature on CTNS mutation screening
      for IC is available to date. In this paper, by using the whole exome sequencing
      and Sanger sequencing, we identified two novel CTNS splicing deletions in a
      Chinese IC family, one at the donor site of exon 6 of CTNS (IVS6+1, del G) and
      the other at the acceptor site of exon 8 (IVS8-1, del GT). These data give
      information for the genetic counseling of the IC that occurred in Chinese
      population. 

PMID- 25866838
TI  - Attention deficit-hyperactivity disorder symptoms and daytime voiding symptoms in
      children with primary enuresis: an observational study to evaluate the
      effectiveness of desmopressin treatment.
AB  - PURPOSE: To evaluate the effectiveness of presence of desmopressin in treating
      primary enuresis (PE) for children with attention deficit-hyperactivity disorder
      (ADHD) symptoms. MATERIALS AND METHODS: Children aged from 5 to 12 years with the
      chief complaint of PE treated with desmopressin were enrolled in pediatric
      urology clinics. The parent-reported SNAP-IV questionnaire was used to evaluate
      ADHD symptoms (cut-off value: 90th percentile). Voiding symptoms were assessed by
      the Dysfunctional Voiding Scoring System (DVSS) questionnaire. The responses to
      desmopressin were analyzed in children with and without ADHD symptoms. RESULTS:
      The study sample comprised 68 children; 27 (39.7%) presented with ADHD symptoms
      and 41 (60.3%) with non-ADHD symptoms. The children collected from a tertiary
      referral center may explain the high prevalence of ADHD symptoms in the present
      study. The total DVSS score in the ADHD symptoms group was significantly higher
      than in the non-ADHD symptoms group (7.72 versus 5.65, P=0.05). In the ADHD
      symptoms group, there were significantly higher score in the "pee 1-2 times/day"
      and "can't wait" subscales of DVSS and lower sleep quality based on the Pediatric
      Sleep Quality questionnaire, as well as significantly lower peak flow rate and
      voided volume. The responses to desmopressin for enuresis were comparable between
      children with ADHD and non-ADHD symptoms. CONCLUSIONS: Approximately 39.7% of PE
      children presented with ADHD symptoms at urologic clinics. PE children with ADHD
      symptoms had higher risk of daytime LUTS and comparable response to desmopressin
      treatment for PE. To evaluate ADHD symptoms and daytime voiding symptoms is
      important in children with PE.

PMID- 25866839
TI  - Influence of whitening gel application protocol on dental color change.
AB  - OBJECTIVES: To evaluate the influence of different whitening protocols on the
      efficacy of 35% hydrogen peroxide (HP) tooth whitening and gel pH and
      concentration. MATERIAL AND METHODS: Eighty-four enamel/dentin discs from bovine
      incisors were used. The baseline color was measured with a spectrophotometer. Two
      sessions of in-office whitening with 35% HP were performed under different
      protocols: G1: 3 applications of HP (10 min each) per session; G2: 1 application
      of 30 min per session; G3: 1 application of 40 min per session, with no gel
      replenishment within session for groups 2 and 3. HP titration and pH evaluation
      at baseline, after 10, 30, and 40 min were also performed. The final color was
      measured 24 h after the 1st and 2nd whitening sessions. Data were submitted to
      Repeated Measures ANOVA and Tukey's test. RESULTS: For color evaluation, no
      differences were observed among groups after two sessions. HP titration showed no
      drop on concentration after 10, 30, or 40 min. The pH was 5.54 at baseline and
      5.41 after 40 min. CONCLUSION: Replenishment or extended application time of in
      office whitening gel does not affect gel pH and concentration, a fact that
      supports the similar effectiveness of whitening observed among the tested
      protocols.

PMID- 25866840
TI  - Numerical study on 4-1 coal seam of Xiaoming mine in ascending mining.
AB  - Coal seams ascending mining technology is very significant, since it influences
      the safety production and the liberation of dull coal, speeds up the construction
      of energy, improves the stability of stope, and reduces or avoids deep hard rock
      mining induced mine disaster. Combined with the Xiaoming ascending mining mine 4
      1, by numerical calculation, the paper analyses ascending mining 4-1 factors,
      determines the feasibility of ascending mining 4-1 coalbed, and proposes roadway
      layout program about working face, which has broad economic and social benefits. 

PMID- 25866841
TI  - Intelligent topical sentiment analysis for the classification of e-learners and
      their topics of interest.
AB  - Every day, huge numbers of instant tweets (messages) are published on Twitter as
      it is one of the massive social media for e-learners interactions. The options
      regarding various interesting topics to be studied are discussed among the
      learners and teachers through the capture of ideal sources in Twitter. The common
      sentiment behavior towards these topics is received through the massive number of
      instant messages about them. In this paper, rather than using the opinion
      polarity of each message relevant to the topic, authors focus on sentence level
      opinion classification upon using the unsupervised algorithm named bigram item
      response theory (BIRT). It differs from the traditional classification and
      document level classification algorithm. The investigation illustrated in this
      paper is of threefold which are listed as follows: (1) lexicon based sentiment
      polarity of tweet messages; (2) the bigram cooccurrence relationship using naive
      Bayesian; (3) the bigram item response theory (BIRT) on various topics. It has
      been proposed that a model using item response theory is constructed for topical
      classification inference. The performance has been improved remarkably using this
      bigram item response theory when compared with other supervised algorithms. The
      experiment has been conducted on a real life dataset containing different set of
      tweets and topics. 

PMID- 25866842
TI  - Extended spectrum beta-lactamase carriage state among elderly nursing home
      residents in Beirut.
AB  - INTRODUCTION: ESBL-producing Enterobacteriaceae can cause severe infections, but
      they are also isolated from the stool of asymptomatic subjects. Faecal carriage
      of such organism is poorly understood. METHODS: First phase of the study was
      cross-sectional with prevalence and epidemiology of ESBL faecal carriage in two
      nursing homes in Beirut: 57 residents in the first (NH1) and 151 residents in the
      second (NH2). In second phase, faecal swabs from cohort of NH1 residents were
      examined for carriage at six-week intervals over three-month period. Residents'
      charts were reviewed to assess carriage risk factors. RESULTS: Over 3 consecutive
      samplings at NH1, 81% of residents were at least one-time carriers with 50% at
      the first round, 60.4% at the second, and 74.5% at the last one. At NH2, 68.2% of
      residents were carriers. Constipation (in NH1) and antibiotic intake (in NH2)
      were significantly associated with higher ESBL faecal carriage while the length
      of stay at the nursing home (in NH2) was associated with less carriage.
      CONCLUSION: Faecal carriage of ESBL-producing Enterobacteriaceae is high among
      nursing home patients in Beirut. The rate of carriage changes rapidly and
      significantly over time either with multiple factors playing a possible role like
      outbreak spreading, antibiotic, and health care system exposure.

PMID- 25866843
TI  - Assessment of Noise Exposure to Children: Considerations for the National
      Children's Study.
AB  - Evidence has been accruing to indicate that young children are vulnerable to
      noise in their physical environment. A literature review identified that, in
      addition to hearing loss, noise exposure is associated with negative birth
      outcomes, reduced cognitive function, inability to concentrate, increased
      psychosocial activation, nervousness, feeling of helplessness, and increased
      blood pressure in children. While increasing attention has been given to the
      health effects of noise in children, research about noise exposure is sparse and
      often the measure of exposure is simply proximity to a noise source. The U.S.
      National Children's Study (NCS) provides a unique opportunity to investigate
      noise exposures to pregnant women and children using a number of assessment
      modalities at different life stages. Measurement of noise levels in homes and
      other environments, personal dosimetry measurements made over a period of days,
      and questionnaires addressing sources of noise in the environment, annoyance to
      noise, perceived noise level, use of head phones and ear buds, noisy activity
      exposures, and occupational exposures, are planned for evaluation within the NCS
      Vanguard pilot study. We describe the NCS planned approach to addressing noise
      exposure assessment in study visits over a child's lifetime.

PMID- 25866844
TI  - What motivates participation in HIV cure trials? A call for real-time assessment
      to improve informed consent.
AB  - HIV cure research, a diverse set of studies aimed at eradicating or greatly
      reducing HIV in latent reservoirs, has become a strategic priority for global
      AIDS research. However, in early-phase HIV cure research there are ethical
      challenges related to the uncertainty around potential risks and the risk-benefit
      balance. Similar to clinical trials in other disease areas, these concerns may
      impact clinical trial participants' comprehension and decision making. Here we
      suggest attention to the terminology used to describe HIV cure research that may
      promote therapeutic misconception, and exploration of the decision-making
      influences and processes of those who accept and decline participation in HIV
      cure trials. These data will facilitate efforts to improve protocols and informed
      consent based on an understanding of participant preferences and needs.

PMID- 25866846
TI  - MMap: Fast Billion-Scale Graph Computation on a PC via Memory Mapping.
AB  - Graph computation approaches such as GraphChi and TurboGraph recently
      demonstrated that a single PC can perform efficient computation on billion-node
      graphs. To achieve high speed and scalability, they often need sophisticated data
      structures and memory management strategies. We propose a minimalist approach
      that forgoes such requirements, by leveraging the fundamental memory mapping
      (MMap) capability found on operating systems. We contribute: (1) a new insight
      that MMap is a viable technique for creating fast and scalable graph algorithms
      that surpasses some of the best techniques; (2) the design and implementation of
      popular graph algorithms for billion-scale graphs with little code, thanks to
      memory mapping; (3) extensive experiments on real graphs, including the 6.6
      billion edge YahooWeb graph, and show that this new approach is significantly
      faster or comparable to the highly-optimized methods (e.g., 9.5* faster than
      GraphChi for computing PageRank on 1.47B edge Twitter graph). We believe our work
      provides a new direction in the design and development of scalable algorithms.
      Our packaged code is available at http://poloclub.gatech.edu/mmap/.

PMID- 25866845
TI  - A Novel Modality for Facet Joint Denervation: Cooled Radiofrequency Ablation for
      Lumbar Facet Syndrome. A Case Series.
AB  - BACKGROUND: While cooled radiofrequency ablation (C-RFA) appears to be a
      promising technology for joint denervation, outcomes of this technique for the
      treatment of lumbar facet syndrome have not been described. We report clinical
      outcomes in a case series of patients treated with C-RFA for lumbar facet
      syndrome. METHODS: Consecutive patients aged 18-60 years diagnosed with lumbar
      facet syndrome, confirmed by >=75% symptom relief with at least one set of
      diagnostic medial branch nerve blocks, who underwent C-RFA between January 2007
      and December 2013 in an urban academic pain center were included. The respective
      proportions of participants who reported >=50% improvement in pain and in
      function were calculated. Change in median NRS score, daily morphine equivalent
      consumption (DME), and medication quantification scale III (MQS III) score were
      measured. RESULTS: Twelve patients underwent C-RFA; three were lost to follow-up.
      The median and 25%-75% interquartile range (IQR) for age was 44 years (35, 54).
      The median duration of follow-up was 34 months, IQR (21, 55). The percentage and
      95% confidence interval (CI) of patients who reported >=50% improvement in pain
      was 33% CI (12%, 64%) and in function was 78%, CI (41%, 96%). There was no
      significant change in DME or MSQ III score. Approximately 50% of patients sought
      additional healthcare by long-term follow-up. No complications were reported.
      CONCLUSIONS: This case series suggests that C-RFA may improve function and to a
      lesser degree pain at long-term follow-up. A randomized, controlled trial is
      warranted.

PMID- 25866847
TI  - Estimating Drivers' Stress from GPS Traces.
AB  - Driving is known to be a daily stressor. Measurement of driver's stress in real
      time can enable better stress management by increasing self-awareness. Recent
      advances in sensing technology has made it feasible to continuously assess
      driver's stress in real-time, but it requires equipping the driver with these
      sensors and/or instrumenting the car. In this paper, we present "GStress", a
      model to estimate driver's stress using only smartphone GPS traces. The GStress
      model is developed and evaluated from data collected in a mobile health user
      study where 10 participants wore physiological sensors for 7 days ( for an
      average of 10.45 hours/day) in their natural environment. Each participant
      engaged in 10 or more driving episodes, resulting in a total of 37 hours of
      driving data. We find that major driving events such as stops, turns, and braking
      increase stress of the driver. We quantify their impact on stress and thus
      construct our GStress model by training a Generalized Linear Mixed Model (GLMM)
      on our data. We evaluate the applicability of GStress in predicting stress from
      GPS traces, and obtain a correlation of 0.72. By obviating any burden on the
      driver or the car, we believe, GStress can make driver's stress assessment
      ubiquitous.

PMID- 25866848
TI  - Mesostructured zeolites: bridging the gap between zeolites and MCM-41.
AB  - Surfactant-templating is one of the most versatile and useful techniques to
      implement mesoporous systems into solid materials. Various strategies based on
      various interactions between surfactants and solid precursors have been explored
      to produce new structures. Zeolites are invaluable as size- and shape-selective
      solid acid catalysts. Nevertheless, their micropores impose limitations on the
      mass transport of bulky feed and/or product molecules. Many studies have
      attempted to address this by utilizing surfactant-assisting technology to
      alleviate the diffusion constraints. However, most efforts have failed due to
      micro/mesopore phase separation. Recently, a new technique combining the uses of
      cationic surfactants and mild basic solutions was introduced to synthesise
      mesostructured zeolites. These materials sustain the unique characteristics of
      zeolites (i.e., strong acidity, crystallinity, microporosity, and hydrothermal
      stability), including tunable mesopore sizes and degrees of mesoporosity. The
      mesostructured zeolites are now commercially available through Rive Technology,
      and show superior performance in VGO cracking. This feature article provides an
      overview of recent explorations in the introduction of mesoporosity into zeolites
      using surfactant-templating techniques. Various porous materials, preparation
      methods, physical and catalytic properties of mesostructured zeolites will be
      discussed. 

PMID- 25866849
TI  - Orbital change manipulation metal-insulator transition temperature in W-doped
      VO2.
AB  - A series of epitaxial V1-xWxO2 (0 <= x <= 0.76%) nanocrystalline films on c-plane
      sapphire substrates have been successfully synthesized. Orbital structures of V1
      xWxO2 films with monoclinic and rutile states have been investigated by
      ultraviolet-infrared spectroscopy combined with first principles calculations.
      Experimental and calculated results show that the overlap of pi* and d? orbitals
      increases with increasing W doping content for the rutile state. Meanwhile, in
      the monoclinic state, the optical band gap decreases from 0.65 to 0.54 eV with
      increasing W doping concentration. Clear evidence is found that the V1-xWxO2 thin
      film phase transition temperature change comes from orbital structure variations.
      This shows that, with increasing W doping concentration, the decrease of rutile
      d? orbital occupancy can reduce the strength of V-V interactions, which finally
      results in phase transition temperature decrease. The experimental results reveal
      that the d? orbital is very important for the VO2 phase transition process. Our
      findings open a possibility to tune VO2 phase transition temperature through
      orbital engineering. 

PMID- 25866850
TI  - Intramolecular vibrational redistribution in the non-radiative excited state
      decay of uracil in the gas phase: an ab initio molecular dynamics study.
AB  - We report a study of intramolecular vibrational distribution (IVR) occurring in
      the electronic ground state of uracil (S0) in the gas phase, following
      photoexcitation in the lowest energy bright excited state (Spi) and decay through
      the ethylene-like Spi/S0 Conical Intersection (CI-0pi). To this aim we have
      performed 20 independent ab initio molecular dynamics simulations starting from
      CI-0pi (ten of them with 1 eV kinetic energy randomly distributed over the
      different molecular degrees of freedom) and 10 starting from the ground state
      minimum (Franck-Condon, FC, point), with the excess kinetic energy equal to the
      energy gap between CI-0pi and the FC point. The simulations, exploiting PBE0/6
      31G(d) calculations, were performed over an overall period of 10 ps. A thorough
      statistical analysis of the variation of the geometrical parameters of uracil
      during the simulation time and of the distribution of the kinetic energy among
      the different vibrational degrees of freedom provides a consistent picture of the
      IVR process. In the first 0-200 fs the structural dynamics involve mainly the
      recovery of the average planarity. In the 200-600 fs time range, a substantial
      activation of CO and NH degrees of freedom is observed. After 500-600 fs most of
      the geometrical parameters reach average values similar to those found after 10
      ps, though the system cannot be considered to be in equilibrium yet. 

PMID- 25866851
TI  - Optical properties of a conjugated-polymer-sensitised solar cell: the effect of
      interfacial structure.
AB  - Dye-sensitised solar cells (DSSCs) have sparked considerable interest over two
      decades. Recently, a method of polymer-wire sensitisation was demonstrated; the
      polymer is suggested to form a hole transport pathway (wire) following initial
      charge separation. We predict the optical properties of this polymer in various
      interfacial configurations, including the effects of chain length and attachment
      to {100} or {101} TiO2 facets. Contrary to most DSSCs, the {100} facet model best
      describes the experimental spectrum, predicting a relative thickness of 5.7 +/-
      0.2 MUm, although {101} attachment, if implemented, may improve collection
      efficiency. Long chains are optimal, and stable attachment sites show minimal
      differences to absorbance in the major solar emission (visible) band.
      Combinations of {100}, {101}, and pseudo-bulk TiO2 models in three-parameter fits
      to experiment confirm the relative importance of the {100} facet. 

PMID- 25866852
TI  - Gas-phase rate coefficients of the reaction of ozone with four sesquiterpenes at
      295 +/- 2 K.
AB  - The rate coefficients of the reaction of ozone with the four atmospherically
      relevant sesquiterpenes beta-caryophyllene, alpha-humulene, alpha-cedrene and
      isolongifolene were investigated at 295 +/- 2 K and atmospheric pressure by at
      least two independent experimental investigations for each reaction. Relative
      rate experiments were carried out in a flow tube using two different experimental
      approaches with GC-MS detection (RR 1) and PTR-MS analysis (RR 2) as the
      analytical techniques. Absolute rate coefficients were determined in a stopped
      flow experiment following the ozone depletion by means of UV spectroscopy. The
      average rate coefficients from the combined investigations representing the mean
      values of the different experimental methods are (unit: cm(3) molecule(-1) s(
      1)): k(O3+beta-caryophyllene) = (1.1 +/- 0.3) * 10(-14) (methods: RR 1, RR 2,
      absolute), k(O3+alpha-humulene) = (1.2 +/- 0.3) * 10(-14) (RR 1, RR 2),
      k(O3+alpha-cedrene) = (1.7 +/- 0.5) * 10(-16) (RR 2, absolute) and
      k(O3+isolongifolene) = (1.1 +/- 0.5) * 10(-17) (RR 2, absolute). The high
      ozonolysis rate coefficients for beta-caryophyllene and alpha-humulene agree well
      with the results by Shu and Atkinson (Int. J. Chem. Kinet., 1994, 26) and lead to
      short atmospheric lifetimes of about two minutes with respect to the ozone
      reaction. The relatively small rate coefficients for alpha-cedrene and
      isolongifolene differ from the available literature values by a factor of about
      2.5-6. Possible reasons for the deviations are discussed. Finally, calibrated
      sesquiterpene FT-IR spectra were recorded for the first time. 

PMID- 25866853
TI  - Electro-catalytic oxidation of hemicelluloses at the Au electrode.
AB  - The recently reported electro-catalytic reaction mechanism for the oxidation of
      cellulose is proposed to work also for the electro-oxidation of other
      polysaccharides (e.g. hemicelluloses). In this report, the electrochemical
      reactivity of some hemicelluloses (xylan, arabinoxylan, glucomannan, xyloglucan,
      and glucuronoxylan) in 1.3 M NaOH solution is described. The electrochemical
      property of each of the studied hemicelluloses at the Au electrode surface was
      characterized by cyclic voltammetry. Xylan, xyloglucan and glucuronoxylan were
      found to be electrochemically active. Electrochemical properties of xylan were
      further studied by electrochemical impedance spectroscopy. The electrochemical
      reaction products of xylan, obtained by extensive electrolysis of the xylan
      solution by cyclic voltammetry, were characterized by FTIR spectroscopy, (13)C
      NMR spectroscopy, SEM and TEM. The structural studies suggest that the oxidized
      xylan is a functional material where some of the OH-groups have been oxidized to
      carboxyl groups making that part of the oxidation product soluble in water under
      ambient conditions (23  degrees C, pH 7). The other part remains insoluble in
      water and contains Au nanoparticles. This work indicates that other
      polysaccharides than cellulose can also be electrochemically oxidized. 

PMID- 25866855
TI  - Small regulatory RNAs and the fine-tuning of plant-bacteria interactions.
AB  - Small regulatory RNAs (sRNAs) play a key role in many physiological and adaptive
      responses in bacteria. Faced with rapidly changing environments, it is more
      advantageous for bacteria to use sRNA-mediated responses than regulation by
      protein transcriptional factors, as sRNAs act at the post-transcriptional level
      and require less energy and time for their synthesis and turnover. The use of RNA
      deep sequencing has provided hundreds of sRNA candidates in different bacterial
      species that interact with plants. Here, we review the most recent results for
      the involvement of bacterial sRNAs in beneficial as well as deleterious plant
      bacteria interactions. We describe the current view for the role of sRNAs, which
      are suggested to improve competition for both niches and resources in plant
      interacting bacteria. These sRNAs also help plant-associated bacteria
      individually adapt to the rapidly changing conditions to which they are exposed,
      during different stages of this interaction.

PMID- 25866854
TI  - Membrane adhesion and the formation of heterogeneities: biology, biophysics, and
      biotechnology.
AB  - Membrane adhesion is essential to many vital biological processes. Sites of
      membrane adhesion are often associated with heterogeneities in the lipid and
      protein composition of the membrane. These heterogeneities are thought to play
      functional roles by facilitating interactions between proteins. However, the
      causal links between membrane adhesion and membrane heterogeneities are not
      known. Here we survey the state of the field and indicate what we think are
      understudied areas ripe for development. 

PMID- 25866856
TI  - Improving intercropping: a synthesis of research in agronomy, plant physiology
      and ecology.
AB  - Intercropping is a farming practice involving two or more crop species, or
      genotypes, growing together and coexisting for a time. On the fringes of modern
      intensive agriculture, intercropping is important in many subsistence or low
      input/resource-limited agricultural systems. By allowing genuine yield gains
      without increased inputs, or greater stability of yield with decreased inputs,
      intercropping could be one route to delivering 'sustainable intensification'. We
      discuss how recent knowledge from agronomy, plant physiology and ecology can be
      combined with the aim of improving intercropping systems. Recent advances in
      agronomy and plant physiology include better understanding of the mechanisms of
      interactions between crop genotypes and species - for example, enhanced resource
      availability through niche complementarity. Ecological advances include better
      understanding of the context-dependency of interactions, the mechanisms behind
      disease and pest avoidance, the links between above- and below-ground systems,
      and the role of microtopographic variation in coexistence. This improved
      understanding can guide approaches for improving intercropping systems, including
      breeding crops for intercropping. Although such advances can help to improve
      intercropping systems, we suggest that other topics also need addressing. These
      include better assessment of the wider benefits of intercropping in terms of
      multiple ecosystem services, collaboration with agricultural engineering, and
      more effective interdisciplinary research.

PMID- 25866857
TI  - Understanding allergy and cancer risk:   what are the barriers?
AB  - Evidence suggests that allergic immune responses can protect against some types
      of cancer. What are the possible underlying mechanisms, and can allergic
      reactions be harnessed for anticancer therapy?

PMID- 25866858
TI  - In memoriam: Dr John A. Gray III.

PMID- 25866859
TI  - Re: Is physician assistant autonomy inevitable?

PMID- 25866860
TI  - Ice Hockey Summit II: zero tolerance for head hits and fighting.
AB  - OBJECTIVE: To present currently known basic science and on-ice influences of
      sport-related concussion (SRC) in hockey, building on the Ice Hockey Summit I
      action plan (2011) to reduce SRC. METHODS: The prior summit proceedings included
      an action plan intended to reduce SRC. As such, the proceedings from Summit I
      served as a point of departure, for the science and discussion held during Summit
      II (Mayo Clinic, Rochester MN, October 2013). Summit II focused on (1) Basic
      Science of Concussions in Ice Hockey: Taking Science Forward; (2) Acute and
      Chronic Concussion Care: Making a Difference; (3) Preventing Concussions via
      Behavior, Rules, Education and Measuring Effectiveness; (4) Updates in Equipment:
      their Relationship to Industry Standards; and (5) Policies and Plans at State,
      National and Federal Levels to reduce SRC. Action strategies derived from the
      presentations and discussion described in these sectors were subsequently voted
      on for purposes of prioritization. The following proceedings include knowledge
      and research shared by invited faculty, many of whom are health care providers
      and clinical investigators. RESULTS: The Summit II evidence-based action plan
      emphasizes the rapidly evolving scientific content of hockey SRC. It includes the
      most highly prioritized strategies voted on for implementation to decrease
      concussion. CONCLUSIONS: The highest priority action items identified from the
      Summit includes the following: (1) eliminate head hits from all levels of ice
      hockey, (2) change body-checking policies, and (3) eliminate fighting in all
      amateur and professional hockey.

PMID- 25866861
TI  - Understanding the effect of a fluorinated ether on the performance of lithium
      sulfur batteries.
AB  - A high performance Li-S battery with novel fluoroether-based electrolyte was
      reported. The fluorinated electrolyte prevents the polysulfide shuttling effect
      and improves the Coulombic efficiency and capacity retention of the Li-S battery.
      Reversible redox reaction of the sulfur electrode in the presence of fluoroether
      TTE was systematically investigated. Electrochemical tests and post-test analysis
      using HPLC, XPS, and SEM/EDS were performed to examine the electrode and the
      electrolyte after cycling. The results demonstrate that TTE as a cosolvent
      mitigates polysulfide dissolution and promotes conversion kinetics from
      polysulfides to Li2S/Li2S2. Furthermore, TTE participates in a redox reaction on
      both electrodes, forming a solid electrolyte interphase (SEI) which further
      prevents parasitic reactions and thus improves the utilization of the active
      material. 

PMID- 25866862
TI  - In Vitro Evaluation of Antimicrobial Photodynamic Therapy Associated with
      Hydroalcoholic Extracts of Schinopsis brasiliensis Engl.: New Therapeutic
      Perspectives.
AB  - OBJECTIVE: The aim of this study was to evaluate the photodynamic potential of
      extracts of Schinopsis brasiliensis Engl. on bacteria involved in several human
      infections. BACKGROUND DATA: Photodynamic therapy (PDT) involves the interaction
      of light with an appropriate and photosensitizer wavelength, and the prospect of
      existing photosensitive compounds in herbal extracts enhanced by the application
      of laser diode has been promising. METHODS: The antibacterial activity against
      Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Enterococcus
      faecalis was obtained by the disk diffusion method on agar. The laser diode
      InGaAIP was used with 660 nm wavelength, 100 mW, and 4 J/cm(2), and the
      application was performed in a timely manner for 34 sec on each disk tested. The
      groups tested were: Laser and bark extract (B+L+); bark extract only (B+L-);
      Laser and leaf extract (F+L+); leaf extract only (F+L-); Laser and malachite
      green (M+L+); malachite green only (M+L-); and laser only (L+). RESULTS: There
      were significant differences between the B+L- and B+L+ groups (p=0.029) and
      between the L+F- and L+F+ groups (p=0.029) at various concentrations of the
      nebulized extracts of bark and leaf. Among the tested pathogens, S. aureus showed
      the highest zone of inhibition, 24.55+/-0.36 mm in group B+L+, 500 mg.mL(-1).
      CONCLUSIONS: PDT with malachite green was effective, and groups B+L+ and F+L+
      showed excellent activity on the bacteria tested, suggesting the presence of
      photosensitizers in extracts of S. brasiliensis Engl.

PMID- 25866864
TI  - First-Principles Modeling of a Dye-Sensitized TiO2/IrO2 Photoanode for Water
      Oxidation.
AB  - We present a first-principle computational modeling investigation, based on
      density functional theory (DFT) and time-dependent DFT, on the structural,
      electronic, optical, and charge generation properties of the
      semiconductor/dye/catalyst heterointerfaces in a prototypical dye-sensitized
      photoanode for water oxidation. The investigated architecture comprises a Ru(II)
      dye-sensitized TiO2 substrate tethered to an IrO2 nanoparticle catalyst. Our
      realistic modeling strategy and quantitative analysis of the relevant interfacial
      hole/electron transfer reactions indicates the slow hole injection into IrO2 and
      the fast dye excited-state quenching to IrO2 as the primary sources of the
      relatively poor cell efficiency experimentally observed. On the basis of this
      atomistic and electronic structure information, we propose and computationally
      test, against a prototype dye, a new class of Ru(II) sensitizers, which show
      potentially improved photoelectrochemical performances. This study constitutes a
      first step toward the computer-assisted design of new and more efficient
      materials for solar fuels production through dye-sensitized photoelectrochemical
      cells. 

PMID- 25866865
TI  - Centimeter-scale subwavelength photolithography using metal-coated elastomeric
      photomasks with modulated light intensity at the oblique sidewalls.
AB  - By coating polydimethylsiloxane (PDMS) relief structures with a layer of opaque
      metal such as gold, the incident light is strictly allowed to pass through the
      nanoscopic apertures at the sidewalls of PDMS reliefs to expose underlying
      photoresist at nanoscale regions, thus producing subwavelength nanopatterns
      covering centimeter-scale areas. It was found that the sidewalls were a little
      oblique, which was the key to form the nanoscale apertures. Two-sided and one
      sided subwavelength apertures can be constructed by employing vertical and
      oblique metal evaporation directions, respectively. Consequently, two-line and
      one-line subwavelength nanopatterns with programmable feature shapes, sizes, and
      periodicities could be produced using the obtained photomasks. The smallest
      aperture size and line width of 80 nm were achieved. In contrast to the
      generation of raised positive photoresist nanopatterns in phase shifting
      photolithography, the recessed positive photoresist nanopatterns produced in this
      study provide a convenient route to transfer the resist nanopatterns to metal
      nanopatterns. This nanolithography methodology possesses the distinctive
      advantages of simplicity, low cost, high throughput, and nanoscale feature size
      and shape controllability, making it a potent nanofabrication technique to enable
      functional nanostructures for various potential applications. 

PMID- 25866866
TI  - School bullying and drug use later in life: A meta-analytic investigation.
AB  - The main aim of this article is to investigate whether there is a significant
      long-term association between bullying at school and drug use later in life. A
      meta-analysis is presented based on results from major prospective longitudinal
      studies with available unadjusted and adjusted effect sizes. Results are based on
      thorough systematic searches of the literature across 19 databases and 63
      journals. The unadjusted summary effect size suggests that youth who bully are at
      least twice as likely compared with noninvolved students to use drugs later in
      life (OR = 2.22, 95% CI: 1.60-3.07). The adjusted summary effect size is markedly
      reduced to an OR of 1.41 (95% CI: 1.20-1.66) suggesting that a lot of variation
      in the final model is explained by other contributing factors, while bullying has
      a significant yet small effect over and above the contribution of these factors.
      Contributing factors include childhood risks falling within the individual,
      family, and school domains that are significantly associated with both the
      predictor and the outcome. It is concluded that school bullying, drug use, and
      other problem behaviors are intercorrelated; thus, highlighting the need to
      create a meaningful holistic framework for the prevention of drug problems and
      other associated mental, emotional, and behavioral maladies. Implications for
      policy and practice arising from these findings are discussed.

PMID- 25866867
TI  - Efficient pathways of excitation energy transfer from delocalized S2 excitons in
      the peridinin-chlorophyll a-protein complex.
AB  - Excitation energy transfer (EET) in peridinin-chlorophyll-protein (PCP) complexes
      is dominated by the S1 -> Qy pathway, but the high efficiencies cannot be solely
      explained by this one pathway. We postulate that EET from peridinin S2 excitons
      may also be important. We use complete active space configuration interaction
      calculations and the transition density cube method to calculate Coulombic
      couplings between peridinin and chlorophyll a in the PCP complex of the
      dinoflagellate Amphidinium carterae and compare monomeric and dimeric delocalized
      peridinin S2 excited states. Our calculations show that the S2 -> Qy EET pathway
      from peridinin to chlorophyll a is the dominant energy transfer pathway from the
      S2 excited state in PCP, with several values in the sub-picosecond range. This
      result suggests that the S2 -> Qy EET pathway may be responsible for the reported
      chlorophyll a bleaching signature seen in experiment at around 200 fs, and not
      the S2 -> Qx pathway as previously suggested. 

PMID- 25866868
TI  - Cross-Situational Learning of Minimal Word Pairs.
AB  - Cross-situational statistical learning of words involves tracking co-occurrences
      of auditory words and objects across time to infer word-referent mappings.
      Previous research has demonstrated that learners can infer referents across sets
      of very phonologically distinct words (e.g., WUG, DAX), but it remains unknown
      whether learners can encode fine phonological differences during cross
      situational statistical learning. This study examined learners' cross-situational
      statistical learning of minimal pairs that differed on one consonant segment
      (e.g., BON-TON), minimal pairs that differed on one vowel segment (e.g., DEET
      DIT), and non-minimal pairs that differed on two or three segments (e.g., BON
      DEET). Learners performed above chance for all pairs, but performed worse on
      vowel minimal pairs than on consonant minimal pairs or non-minimal pairs. These
      findings demonstrate that learners can encode fine phonetic detail while tracking
      word-referent co-occurrence probabilities, but they suggest that phonological
      encoding may be weaker for vowels than for consonants. 

PMID- 25866869
TI  - The relationship between serum lipids and sudden sensorineural hearing loss: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Sudden sensorineural hearing loss (SSNHL) is a relatively common
      condition that is usually of unknown etiology. A number of individual studies
      have investigated the association between various serum lipids and SSNHL;
      however, the findings have been inconsistent. In an attempt to obtain more
      definitive information on the relationship between serum lipids and SSNHL, we
      carried out a systematic review and meta-analysis. METHODS: Medline, the Cochrane
      Library, and EMBASE were searched using the following key words: lipid,
      cholesterol, triglyceride, fat, serum, blood, sudden hearing loss, hearing loss,
      hearing disorders. Randomized controlled trials, prospective cohort studies, and
      retrospective case-control studies involving patients with SSNHL and healthy
      controls that examined the relationship (reported as odds ratios [OR]) between
      lipid profiles and SSNHL were included. Primary outcomes were total cholesterol
      and low-density lipoprotein cholesterol (LDL-C) concentrations. Secondary
      outcomes were triglyceride, high-density lipoprotein cholesterol, and
      lipoprotein(a) concentrations. RESULTS: A total of 6 case-control studies were
      included in this systematic review/meta-analysis. The total number of
      participants ranged from 30 to 250 in the case group and from 43 to 271 in the
      control group. Meta-analysis revealed no significant difference in total
      cholesterol levels between the case and control groups (pooled OR = 1.79, 95%
      confidence interval [CI] = 0.98 to 3.26, P = 0.057). Likewise, meta-analysis
      revealed no significant difference in LDL-C concentrations between the case and
      control groups (pooled OR = 1.15, 95% CI = 0.64 to 2.07, P = 0.639). Since there
      were an insufficient number of studies reporting data for the secondary outcomes,
      meta-analysis was not possible. CONCLUSIONS: Our results do not provide evidence
      for serum lipids being associated with SSNHL, nor do they definitively rule out
      such an association. Additional studies are needed to ascertain the relationship,
      or lack thereof, between serum lipids and SSNHL.

PMID- 25866870
TI  - The pbrB gene encodes a laccase required for DHN-melanin synthesis in conidia of
      Talaromyces (Penicillium) marneffei.
AB  - Talaromyces marneffei (Basionym: Penicillium marneffei) is a significant
      opportunistic fungal pathogen in patients infected with human immunodeficiency
      virus in Southeast Asia. T. marneffei cells have been shown to become melanized
      in vivo. Melanins are pigment biopolymers which act as a non-specific protectant
      against various stressors and which play an important role during virulence in
      fungi. The synthesis of the two most commonly found melanins in fungi, the
      eumelanin DOPA-melanin and the allomelanin DHN-melanin, requires the action of
      laccase enzymes. The T. marneffei genome encodes a number of laccases and this
      study describes the characterization of one of these, pbrB, during growth and
      development. A strain carrying a PbrB-GFP fusion shows that pbrB is expressed at
      high levels during asexual development (conidiation) but not in cells growing
      vegetatively. The pbrB gene is required for the synthesis of DHN-melanin in
      conidia and when deleted results in brown pigmented conidia, in contrast to the
      green conidia of the wild type. 

PMID- 25866871
TI  - VUV Photofragmentation of CH2I2: The [CH2I-I](*+) Iso-diiodomethane Intermediate
      in the I-Loss Channel from [CH2I2](*.).
AB  - Diiodomethane is an important halocarbon responsible for several atmospheric
      processes like ozone depletion and aerosol particle formation. Despite this, the
      thermochemical data and a detailed analysis of the pathways for the decomposition
      of this halomethane and its molecular ion [CH2I2](*+) are scarce. In this paper
      an investigation of the photodissociation dynamics of the CH2I2 molecule focused
      on the I-loss channel by the photoelectron-photoion coincidence (PEPICO)
      technique and computational methods is reported. The experimental results show
      that upon VUV irradiation the dissociation of the lower electronic ionic states
      of diiodomethane leads only to the CH2I(+) ion and the I atom. The theoretical
      calculations point out that isomerization of [CH2I2](*+) into iso-diiodomethane
      [CH2I-I](*+) may play an important role in the emission of iodine atom as
      compared to direct C-I bond breaking. 

PMID- 25866872
TI  - Counter anion dependent gradual spin transition in a 1D cobalt(ii) coordination
      polymer.
AB  - One Co(ii) SCO coordination polymer [Co(enbzpy)(MU1,5-dca)]n(PF6)n (.PF6) has
      been isolated and characterised structurally and magnetostructurally. The
      properties of .PF6 are compared with the reported perchlorate analogue
      [Co(enbzpy)(MU1,5-dca)]n(ClO4)n (.ClO4). The gradual spin transition in .PF6 in
      contrast to an abrupt spin transition with a hysteresis loop in .ClO4 has been
      analysed in terms of structural factors. 

PMID- 25866874
TI  - Evidence That Up-Regulation of MicroRNA-29 Contributes to Postnatal Body Growth
      Deceleration.
AB  - Body growth is rapid in infancy but subsequently slows and eventually ceases due
      to a progressive decline in cell proliferation that occurs simultaneously in
      multiple organs. We previously showed that this decline in proliferation is
      driven in part by postnatal down-regulation of a large set of growth-promoting
      genes in multiple organs. We hypothesized that this growth-limiting genetic
      program is orchestrated by microRNAs (miRNAs). Bioinformatic analysis identified
      target sequences of the miR-29 family of miRNAs to be overrepresented in age-down
      regulated genes. Concomitantly, expression microarray analysis in mouse kidney
      and lung showed that all members of the miR-29 family, miR-29a, -b, and -c, were
      strongly up-regulated from 1 to 6 weeks of age. Real-time PCR confirmed that miR
      29a, -b, and -c were up-regulated with age in liver, kidney, lung, and heart, and
      their expression levels were higher in hepatocytes isolated from 5-week-old mice
      than in hepatocytes from embryonic mouse liver at embryonic day 16.5. We next
      focused on 3 predicted miR-29 target genes (Igf1, Imp1, and Mest), all of which
      are growth-promoting. A 3'-untranslated region containing the predicted target
      sequences from each gene was placed individually in a luciferase reporter
      construct. Transfection of miR-29 mimics suppressed luciferase gene activity for
      all 3 genes, and this suppression was diminished by mutating the target
      sequences, suggesting that these genes are indeed regulated by miR-29. Taken
      together, the findings suggest that up-regulation of miR-29 during juvenile life
      drives the down-regulation of multiple growth-promoting genes, thus contributing
      to physiological slowing and eventual cessation of body growth. 

PMID- 25866873
TI  - Deciphering the regulatory logic of an ancient, ultraconserved nuclear receptor
      enhancer module.
AB  - Cooperative, synergistic gene regulation by nuclear hormone receptors can
      increase sensitivity and amplify cellular responses to hormones. We investigated
      thyroid hormone (TH) and glucocorticoid (GC) synergy on the Kruppel-like factor 9
      (Klf9) gene, which codes for a zinc finger transcription factor involved in
      development and homeostasis of diverse tissues. We identified regions of the
      Xenopus and mouse Klf9 genes 5-6 kb upstream of the transcription start sites
      that supported synergistic transactivation by TH plus GC. Within these regions,
      we found an orthologous sequence of approximately 180 bp that is highly conserved
      among tetrapods, but absent in other chordates, and possesses chromatin marks
      characteristic of an enhancer element. The Xenopus and mouse approximately 180-bp
      DNA element conferred synergistic transactivation by hormones in transient
      transfection assays, so we designate this the Klf9 synergy module (KSM). We
      identified binding sites within the mouse KSM for TH receptor, GC receptor, and
      nuclear factor kappaB. TH strongly increased recruitment of liganded GC receptor
      and serine 5 phosphorylated (initiating) RNA polymerase II to chromatin at the
      KSM, suggesting a mechanism for transcriptional synergy. The KSM is transcribed
      to generate long noncoding RNAs, which are also synergistically induced by
      combined hormone treatment, and the KSM interacts with the Klf9 promoter and a
      far upstream region through chromosomal looping. Our findings support that the
      KSM plays a central role in hormone regulation of vertebrate Klf9 genes, it
      evolved in the tetrapod lineage, and has been maintained by strong stabilizing
      selection. 

PMID- 25866876
TI  - Kinetics of leukocyte CD11b and CD64 expression in severe sepsis and non
      infectious critical care patients.
AB  - BACKGROUND: Leukocyte surface molecules may improve sepsis diagnostics. Our aim
      was to study whether monocyte and neutrophil CD11b and CD64 expression differs
      between patients with severe sepsis (including septic shock) and intensive care
      unit (ICU) controls, and also to investigate the expression kinetics in patient
      groups. METHODS: Monocyte and neutrophil CD11b and CD64 expression was analyzed
      in 27 patients with severe sepsis, 7 off-pump coronary artery bypass (OPCAB)
      patients, and 8 ICU patients without systemic inflammation in the beginning of
      the treatment using quantitative flow cytometry. Blood samples were collected
      within 48 h of the beginning of severe sepsis, at admission to the ICU for non
      systemic inflammatory response syndrome patients, and on the day of surgery
      before the skin incision for OPCAB patients, and on 2 consecutive days for all
      patients. Ten healthy individuals served as controls. RESULTS: Monocyte and
      neutrophil CD11b and neutrophil CD64 expression was higher in severe sepsis
      patients compared with the other groups (P < 0.05). In severe sepsis, the
      expression decreased over time (P < 0.05). In OPCAB patients, the monocyte and
      neutrophil CD64 expression increased after surgery (P < 0.05). Neutrophil CD64
      expression had the highest and statistically significant area under curves (AUC)
      values for identification of severe sepsis during 3 consecutive days, the highest
      AUC being 0.990 on D0. CONCLUSION: Neutrophil CD64 as well as neutrophil and
      monocyte CD11b expressions were highest in severe sepsis compared with non
      infectious conditions, and thus analyses of their expression may be promising
      approach for sepsis diagnosis in ICU population.

PMID- 25866875
TI  - Minireview: From the bench, toward the clinic: therapeutic opportunities for
      cannabinoid receptor modulation.
AB  - The effects of cannabinoids have been known for centuries and over the past
      several decades two G protein-coupled receptors, CB1 and CB2, that are
      responsible for their activity have been identified. Endogenous lipid-derived
      cannabinergic agents have been found, biosynthetic and catabolic machinery has
      been characterized, and synthetic agents have been designed to modulate these
      receptors. Selective agents including agonists, antagonists, inverse agonists,
      and novel allosteric modulators targeting either CB1 or CB2 have been developed
      to inhibit or augment their basal tone. As a result, the role these receptors
      play in human physiology and their potential therapeutic applications in disease
      states are being elucidated. The CB1 receptor, although ubiquitous, is densely
      expressed in the brain, and CB2 is largely found on cells of immune origin. This
      minireview highlights the role of CB1 in excitotoxic assaults in the brain and
      its potential to limit addiction liability. In addition, it will examine the
      relationship between receptor activity and stimulation of insulin release from
      pancreatic beta-cells, insulin resistance, and feeding behavior leading toward
      obesity. The roles of CB2 in the neuropathology of amyotrophic lateral sclerosis
      and in the central manifestations of chronic HIV infection potentially converge
      at inflammatory cell activation, thereby providing an opportunity for
      intervention. Last, CB2 modulation is discussed in the context of an experimental
      model of postmenopausal osteoporosis. Achieving exquisite receptor selectivity
      and elucidating the mechanisms underlying receptor inhibition and activation will
      be essential for the development of the next generation of cannabinergic-based
      therapeutic agents. 

PMID- 25866877
TI  - Deleterious effects of obesity on physical fitness in pre-pubertal children.
AB  - The prevalence of obesity in children has increased dramatically during the past
      decades in Europe and understanding physical fitness and its components in
      children is critical to design and implement effective interventions. The
      objective of the present study was to analyse the association between physical
      fitness (aerobic, speed, agility, power, flexibility and balance) and body mass
      index (BMI) in pre-pubertal children. A total of 2411 healthy schoolchildren (7
      11 years) participated in this study. Anthropometric characteristics and body
      composition were assessed by skinfold thickness. Physical fitness was measured by
      nine physical fitness tests: endurance running, 20 m running speed, agility,
      handgrip strength, standing long jump and squat jump, sit and reach, medicine
      ball forward throw and static balance. No relevant differences were observed
      between boys and girls regarding anthropometric characteristics, body composition
      and physical fitness. However, overweight and obese children showed significantly
      lower physical fitness levels in endurance running, speed and agility (mean:
      +18.8, +5.5 and +14.5% of time to complete tasks, respectively), lower limb power
      normalised to body mass (-23.3%) and balance tests (number of falls: +165.5%)
      than their normal weight counterparts. On the other hand, obesity did not affect
      handgrip, throwing and flexibility. In conclusion, increased BMI was associated
      with lower performance capabilities limiting proper motor skill development,
      which directly affects the ability of children to take on sports skills. Actions
      undertaken to promote children's wellness and fitness should be prioritised and
      introduced early in life with the aim of enhancing physical fitness as well as
      preventing overweight and obesity. 

PMID- 25866878
TI  - Transport of surface-modified carbon nanotubes through a soil column.
AB  - Carbon nanotubes (CNTs) are widely manufactured nanoparticles, which are being
      utilized in a number of consumer products, such as sporting goods, electronics
      and biomedical applications. Due to their accelerating production and use, CNTs
      constitute a potential environmental risk if they are released to soil and
      groundwater systems. It is therefore essential to improve the current
      understanding of environmental fate and transport of CNTs. The transport and
      retention of CNTs in both natural and artificial media have been reported in
      literature, but the findings widely vary and are thus not conclusive. There are a
      number of physical and chemical parameters responsible for variation in retention
      and transport. In this study, a complete procedure of selected multiwalled carbon
      nanotubes (MWCNTs) is presented starting from their surface modification to a
      complete set of laboratory column experiments at critical physical and chemical
      scenarios. Results indicate that the stability of the commercially available
      MWCNTs are critical with their attached surface functional group which can also
      influence the transport and retention of MWCNT through the surrounding medium. 

PMID- 25866879
TI  - Subunit asymmetry and roles of conformational switching in the hexameric AAA+
      ring of ClpX.
AB  - The hexameric AAA+ ring of Escherichia coli ClpX, an ATP-dependent machine for
      protein unfolding and translocation, functions with the ClpP peptidase to degrade
      target substrates. For efficient function, ClpX subunits must switch between
      nucleotide-loadable (L) and nucleotide-unloadable (U) conformations, but the
      roles of switching are uncertain. Moreover, it is controversial whether working
      AAA+-ring enzymes assume symmetric or asymmetric conformations. Here, we show
      that a covalent ClpX ring with one subunit locked in the U conformation catalyzes
      robust ATP hydrolysis, with each unlocked subunit able to bind and hydrolyze ATP,
      albeit with highly asymmetric position-specific affinities. Preventing U<->L
      interconversion in one subunit alters the cooperativity of ATP hydrolysis and
      reduces the efficiency of substrate binding, unfolding and degradation, showing
      that conformational switching enhances multiple aspects of wild-type ClpX
      function. These results support an asymmetric and probabilistic model of AAA+
      ring activity. 

PMID- 25866880
TI  - Translational control of the cytosolic stress response by mitochondrial ribosomal
      protein L18.
AB  - In response to stress, cells attenuate global protein synthesis but permit
      efficient translation of mRNAs encoding heat-shock proteins (HSPs). Although
      decades have passed since the first description of the heat-shock response, how
      cells achieve translational control of HSP synthesis remains enigmatic. Here we
      report an unexpected role for mitochondrial ribosomal protein L18 (MRPL18) in the
      mammalian cytosolic stress response. MRPL18 bears a downstream CUG start codon
      and generates a cytosolic isoform in a stress-dependent manner. Cytosolic MRPL18
      incorporates into the 80S ribosome and facilitates ribosome engagement on mRNAs
      selected for translation during stress. MRPL18 knockdown has minimal effects on
      mitochondrial function but substantially dampens cytosolic HSP expression at the
      level of translation. Our results uncover a hitherto-uncharacterized stress
      adaptation mechanism in mammalian cells, which involves formation of a 'hybrid'
      ribosome responsible for translational regulation during the cytosolic stress
      response. 

PMID- 25866881
TI  - The ubiquitination of the influenza A virus PB1-F2 protein is crucial for its
      biological function.
AB  - The aim of the present study was to identify what influences the short half-life
      of the influenza A virus PB1-F2 protein and whether a prolonged half-life affects
      the properties of this molecule. We hypothesized that the short half-life of PB1
      F2 could conceal the phenotype of the protein. Because proteasome degradation
      might be involved in PB1-F2 degradation, we focused on ubiquitination, a common
      label for proteasome targeting. A cluster of lysine residues was demonstrated as
      an ubiquitination acceptor site in evolutionary and functionally distinct
      proteins. The PB1-F2 sequence alignment revealed a cluster of lysines on the
      carboxy terminal end of PB1-F2 in almost all of the GenBank sequences available
      to date. Using a proximity ligation assay, we identified ubiquitination as a
      novel posttranslational modification of PB1-F2. Changing the lysines at positions
      73, 78, and 85 to arginines suppressed the ubiquitination of A/Puerto Rico/8/1934
      (H1N1)-derived PB1-F2. The mutation of the C-terminal lysine residue cluster
      positively affected the overall expression levels of avian A/Honk Kong/156/1997
      (H5N1)- and mammalian A/Puerto Rico/8/1934 (H1N1)-derived PB1-F2. Moreover,
      increased PB1-F2 copy numbers strengthened the functions of this virus in the
      infected cells. The results of a minigenome luciferase reporter assay revealed an
      enhancement of viral RNA-dependent RNA polymerase activity in the presence of
      stabilized PB1-F2, regardless of viral origin. IFNbeta antagonism was enhanced in
      293T cells transfected with a plasmid expressing stabilized K->R mutant variants
      of PB1-F2. Compared with PB1-F2 wt, the loss of ubiquitination enhanced the
      antibody response after DNA vaccination. In summary, we revealed that PB1-F2 is
      an ubiquitinated IAV protein, and this posttranslational modification plays a
      central role in the regulation of the biological functions of this protein. 

PMID- 25866883
TI  - [Mental disorders and rehabilitation].

PMID- 25866882
TI  - Adapting human videofluoroscopic swallow study methods to detect and characterize
      dysphagia in murine disease models.
AB  - This study adapted human videofluoroscopic swallowing study (VFSS) methods for
      use with murine disease models for the purpose of facilitating translational
      dysphagia research. Successful outcomes are dependent upon three critical
      components: test chambers that permit self-feeding while standing unrestrained in
      a confined space, recipes that mask the aversive taste/odor of commercially
      available oral contrast agents, and a step-by-step test protocol that permits
      quantification of swallow physiology. Elimination of one or more of these
      components will have a detrimental impact on the study results. Moreover, the
      energy level capability of the fluoroscopy system will determine which swallow
      parameters can be investigated. Most research centers have high energy
      fluoroscopes designed for use with people and larger animals, which results in
      exceptionally poor image quality when testing mice and other small rodents.
      Despite this limitation, we have identified seven VFSS parameters that are
      consistently quantifiable in mice when using a high energy fluoroscope in
      combination with the new murine VFSS protocol. We recently obtained a low energy
      fluoroscopy system with exceptionally high imaging resolution and magnification
      capabilities that was designed for use with mice and other small rodents.
      Preliminary work using this new system, in combination with the new murine VFSS
      protocol, has identified 13 swallow parameters that are consistently quantifiable
      in mice, which is nearly double the number obtained using conventional (i.e.,
      high energy) fluoroscopes. Identification of additional swallow parameters is
      expected as we optimize the capabilities of this new system. Results thus far
      demonstrate the utility of using a low energy fluoroscopy system to detect and
      quantify subtle changes in swallow physiology that may otherwise be overlooked
      when using high energy fluoroscopes to investigate murine disease models. 

PMID- 25866884
TI  - [Rehabilitation of patients with acid-base and fluid balance disorders with short
      bowel syndrome after ileostomies].
AB  - BACKGROUND: Patients with ileostomies regularly suffer from short bowel syndrome
      or high volume output associated with loss of absorptive surface and subsequent
      impairment of absorption for drugs and different nutrients resulting in
      electrolyte and fluid balance disorders as well as renal insufficiency.
      Adaptation of these fundamental functions of the gut with adequate fluid uptake,
      absorption of sufficient different nutrients and vitamins represents a major
      challenge to rehabilitate these patients shortly after surgery. Patients with
      ileostomy often develop metabolic acidosis with normal anion gap. In our
      retrospective study we would like to draw attention to these metabolic disorders
      in patients with ileostomy in comparison to patients with colostomy and patients
      undergoing gastrectomy for gastric cancer. METHODS: In the period from 2005 to
      2012 we examined 164 patients with ileostomy in our rehabilitation clinic, 109
      patients with colostomy and 193 patients after surgery for gastric cancer of the
      possible presence of metabolic acidosis by using capillary blood gas analysis
      (metabolic acidosis was anticipated, if base excess was <=- 3,0 mmol/l). Patients
      are treated as inpatients both in early stage and for follow-up rehabilitation.
      The length of time in our rehabilitation clinic lies in between 24-28 days. On
      the basis of random samples we tested blood samples in 19 patients with ileostomy
      in succession for ferritin, folic acid, zinc, selenium and vitamin B12.
      Statistical analysis comprised the classical intervals (mean and standard
      deviation, range and T-test for dependent and independent samples). RESULTS: In
      total we tested 164 inpatients with ileostomy in our rehabilitation clinic
      (median age 67.4 years, range 19-79 years). Surgery for ileostomy took place
      about 1.4 months on average ago (range 1/4-56 months). 60 (36.5%) inpatients
      suffered from metabolic acidosis often combined with renal insufficiency.
      Supportive therapy intravenously administered in 10 patients and sodium
      bicarbonate given by mouth in 40 patients significantly improved metabolic acid
      (base excess improved on average from -7.2 to -3.2 mmol/l, p<0.00138) and renal
      function calculated on the basis of serum creatinine (serum creatinine decreased
      from 1.49 on average to 1.34 mg/dl, p<0.04039). Body weight remained constant
      over the whole period on average with 74 kg. Diuretics did not show any influence
      on the base excess. In 19 patients with ileostomy who did not take any kind of
      supplements, among the parameters tested were a high percentage of zinc (9 of 19
      patients, 47%) and selenium deficiency (13 of 19 patients, 68%). 50 patients with
      ileostomy were younger than 65 years of age and thus in the working age
      population. In the group of patients after gastrectomy because of gastric cancer
      (n=193, median age 69.1 years, range 36-82 years), surgery for gastrectomy took
      place about 1.8 months on average ago and in this group only 14 patients (7%)
      showed metabolic acidosis. In the group of patients with colostomy (n=109, median
      age 69.5 years, range 39-82 years), surgery for colostomy took place about 2.1
      months on average ago and in this group only 6 patients (5.5%) suffered from
      metabolic acidosis. CONCLUSION: Medical rehabilitation is indicated for patients
      with enterostoma. Acceptance of the enterostoma by the patient himself,
      psychological stabilization, achievement of self-sufficiency in stoma care,
      improvement of physical abilities and finally being fit for full or limited
      employment are the most important objectives in rehabilitation medicine.
      Metabolic acidosis was often found in patients with ileostomy and was an
      important clinical appearance. Blood gas analysis is recommended to verify
      metabolic acidosis and if confirmed sodium bicarbonate and in cases of high
      volume output salt-depleting ileostomy additionally intravenous fluid support
      should be offered controlling body weight in the follow-up. As could be shown by
      our analysis patients with ileostomy should also be tested for zinc and selenium
      deficiency.

PMID- 25866885
TI  - [Can ICF core sets be helpful in preparing a social-medical expert report due to
      incapacity to work?--a first proposal].
AB  - INTRODUCTION: Social-medical expert reports from the German statutory pension
      insurance are essential for the German statutory pension regulatory authority to
      decide whether to grant services regarding participation as well as retirement
      pensions due to incapacity to work.The objective of this investigation is to
      determine whether the ICF Core Sets and other international approaches, such as
      the EUMASS Core Sets or ICF Core Set for vocational rehabilitation cover the
      content of the social-medical expert reports as well as to propose an approach
      how the ICF can be economically used by the social medicine practitioner when
      writing a social-medical expert report. METHOD: A retrospective quantitative
      study design was used to translate a total of 294 social-medical expert reports
      from patients with low back pain (LBP) or chronic widespread pain (CWP) into the
      language of the ICF (linking) by 2 independent health professionals and compare
      the results with the ICF Core Sets for specific health conditions and other
      international approaches. RESULTS: The content of social-medical expert reports
      was largely reflected by the condition specific brief ICF Core Sets, brief ICF
      Core Sets for vocational rehabilitation and EUMASS Core Sets. The weighted Kappa
      statistic for the agreement between the 2 health professionals who translated the
      expert reports were in CWP 0.69 with a bootstrapped confidence interval of 0.67
      0.71 and in LBP 0.73 (0.71-0.74). DISCUSSION: The analyses show that the content
      of social-medical expert reports varies enormously. A combination of a condition
      specific brief ICF Core Set as well as vocational rehabilitation and EUMASS ICF
      Core Sets as well as all ICF-categories from the expert reports that were named
      at least in 50% of it can largely provide a basis for preparing expert reports.
      Within the scope of implementation the need for a specific ICF Core Set for
      expert reports of the German statutory pension insurance should be further
      analyzed and discussed.

PMID- 25866886
TI  - [Rehabilitation in bowel diseases].

PMID- 25866888
TI  - A Lanthanide(III) Triflate Mediated Macrolactonization/Solid-Phase Synthesis
      Approach for Depsipeptide Synthesis.
AB  - The effect of dysprosium(III) triflate on macrolactonization reactions to form
      depsipeptides using MNBA (Shiina's reagent) is reported. Improved yields were
      obtained for the formation of 16-membered depsipeptides using lanthanide triflate
      additives. The use of a macrocyclization strategy permits the use of a
      semiautomated solid-phase synthesis approach for the rapid synthesis of analogues
      of the antibacterial A54556 acyldepsipeptides in only two physical operations,
      requiring only final product purification after cyclization. 

PMID- 25866889
TI  - The rapidly escalating cost of treating colorectal cancer in Australia.
AB  - AIMS: Considerable progress in cancer treatment is leading to better outcomes,
      but the cost of therapy is placing increasing pressure on the health system.
      Understanding the real-world cost of therapies for each stage will become
      increasingly important in informing treatment selection and health policy.
      METHODS: To explore the cost of treating colorectal cancer in the modern era,
      data were entered onto a prospective database at four hospitals. We estimated the
      impact of bevacizumab by using data from July 2009, and projected the likely
      impact of the recent listing of cetuximab. The utility of these data for
      estimating the cost-effectiveness of treatment was explored. RESULTS: Cancer
      stage and age at diagnosis were major determinants of treatment received and the
      associated cost. The cost of early stage disease has not substantially changed
      whereas therapies such as oxaliplatin and irinotecan were significant
      contributors to substantial increases in stage IV disease, now $71,156 per
      patient. Bevacizumab has added at least $10,247 per patient and we estimate that
      cetuximab will add a further $12,022. An exploratory analysis of the cost
      effectiveness of oxaliplatin for adjuvant therapy of stage III colon cancer
      suggests that this is well within the accepted range. CONCLUSION: These data
      suggest that recent progress in the treatment of later stages of colorectal
      cancer is being achieved at significant financial cost. The increased costs of
      managing later stages of disease make an investment in prevention and early
      detection ever more attractive.

PMID- 25866891
TI  - Review of small intestine submucosa extracellular matrix technology in multiple
      difficult-to-treat wound types.
AB  - The extracellular matrix (ECM) of the dermis is a critical structural component
      required for normal wound healing. The ECM, along with its key signaling
      components, provides the support structure necessary for fibroblasts, immune
      cells, and keratinocytes. When ECM activity is dysfunctional, the normal wound
      healing process is compromised, leading to slow, irregular repair, which may
      result in the development of chronic wounds. To replace dysfunctional ECM,
      several strategies have been developed to promote the development of a proper ECM
      or to replace the ECM entirely. One such method is the use of small intestine
      submucosa (SIS) to replace the nonfunctional ECM. Small intestine submucosa
      closely mimics the normal ECM of the human dermis despite being of porcine
      derivation. Small intestine submucosa wound matrix is an example of an available
      ECM-based biomaterial that has demonstrated improvements in wound management in
      the clinical setting. 

PMID- 25866890
TI  - Osmostress-induced apoptosis in Xenopus oocytes: role of stress protein kinases,
      calpains and Smac/DIABLO.
AB  - Hyperosmotic shock induces cytochrome c release and caspase-3 activation in
      Xenopus oocytes, but the regulators and signaling pathways involved are not well
      characterized. Here we show that hyperosmotic shock induces rapid calpain
      activation and high levels of Smac/DIABLO release from the mitochondria before
      significant amounts of cytochrome c are released to promote caspase-3 activation.
      Calpain inhibitors or EGTA microinjection delays osmostress-induced apoptosis,
      and blockage of Smac/DIABLO with antibodies markedly reduces cytochrome c release
      and caspase-3 activation. Hyperosmotic shock also activates the p38 and JNK
      signaling pathways very quickly. Simultaneous inhibition of both p38 and JNK
      pathways reduces osmostress-induced apoptosis, while sustained activation of
      these kinases accelerates the release of cytochrome c and caspase-3 activation.
      Therefore, at least four different pathways early induced by osmostress converge
      on the mitochondria to trigger apoptosis. Deciphering the mechanisms of
      hyperosmotic shock-induced apoptosis gives insight for potential treatments of
      human diseases that are caused by perturbations in fluid osmolarity.

PMID- 25866892
TI  - A prospective randomized trial comparing subatmospheric wound therapy with a
      sealed gauze dressing and the standard vacuum-assisted closure device: a
      supplementary subgroup analysis of infected wounds.
AB  - INTRODUCTION: Subatmospheric pressure wound therapy (SAWT) is commonly used to
      manage infected wounds. However, this practice remains controversial because the
      safety and efficacy of the technique has not been carefully documented. METHODS:
      The authors assessed the safety and efficacy of a sealed gauze dressing with wall
      suction applied (GSUC) compared to vacuum assisted-closure (VAC), both soaked
      with topical antimicrobials. Subjects included 31 hospitalized patients with
      acutely infected wounds compared with 56 patients with noninfected wounds.
      RESULTS: There were significant reductions in wound surface area and volume in
      both infected and noninfected groups; there was no significant difference in the
      rate of change observed in the GSUC vs the VAC arms of the study. In the infected
      group, the reduction in wound surface area was 4.4% per day for GSUC and 4.8% per
      day for VAC. Wound volume was 7.8% per day for GSUC, and 9.7% per day for VAC (P
      < 0.001 for all). Evidence of wound infection in all patients, regardless of
      treatment group, resolved by 96 hours of onset of treatment, and there were no
      complications specifically related to the use of a sealed dressing over infected
      wounds. CONCLUSION: Gauze dressing with wall suction and VAC therapy can be used
      in selected acute, infected wounds and both methods of treatment appear to be
      similarly effective for reducing wound surface area and volume.    .

PMID- 25866893
TI  - Inactivation of mycobacterium smegmatis following exposure to 405-nanometer light
      from a supraluminous diode array.
AB  - OBJECTIVE: To determine the potential for blue light (405 nm) to produce a
      bactericidal effect on Mycobacterium smegmatis. Additionally, the study sought to
      evaluate a series of doses in terms of their respective bactericidal
      capabilities. BACKGROUND DATA: The effect of blue light on Staphylococcus aureus
      has been studied and it was found that a bactericidal outcome can be obtained
      with low doses of blue light. METHODS: M. smegmatis was tested because of the
      recent appearance of the Mycobacterium family of organisms as a public health
      threat among persons receiving tattoos. The organism was treated in vitro with
      405 nm light emitted from a supraluminous diode (SLD) array. Doses of 60 Jcm-2,
      90 Jcm-2, 120 Jcm-2, 150 Jcm-2, 180 Jcm-2, 215 Jcm-2, and 250 Jcm-2 were used.
      Colony counts were performed and compared to untreated controls using Student t
      tests and one-way ANOVA with Tukey post hoc analysis. RESULTS: The results
      revealed statistically significant bactericidal effects of the blue light on M.
      smegmatis (F6, 28 = 50.518, P = 0.000). The treatment reduced the number of
      bacterial colonies at all doses, but 60 Jcm-2 did not produce a statistically
      significant kill rate. All other doses produced a significant kill rate with 120
      Jcm-2, 150 Jcm-2, and 215 Jcm-2, demonstrating the most effective kill rates of
      98.3%, 96.7%, and 100%, respectively. CONCLUSIONS: Appropriate doses of 405 nm
      light from an SLD array can kill M. smegmatis in vitro. A dose of at least 100
      Jcm-2 dose is needed for the most effective inactivation of the organism. The
      dose response for this organism to blue light is not linear. Some degree of
      effectiveness is lost at 180 Jcm-2 and 250 Jcm-2.  .

PMID- 25866894
TI  - Successful management of a case of primary cutaneous mucormycosis in an
      immunocompetent host.
AB  - Primary cutaneous mucormycosis is a rare disease in the immunocompetent, and
      research on this condition is limited to case reports. Clinical presentation is
      not sufficiently distinctive to allow a diagnosis and the immunocompetent state
      precludes even the suspicion of the condition. There is agreement in literature
      regarding the absence of guidelines for its treatment. Most reports have used a
      combination of aggressive and repeated surgical debridement and systemic
      antifungals, usually amphotericin B. The authors propose the use of
      vacuumassisted closure technology in managing these wounds with a possible role
      in decreasing the number and extent of debridement and limiting deeper tissue
      damage.    . 

PMID- 25866895
TI  - A feasibility study of dignity therapy in patients with stage IV colorectal
      cancer actively receiving second-line chemotherapy.
AB  - BACKGROUND: Randomized controlled trials support the use of dignity therapy (DT)
      in palliative care patients late in the course of their disease, but little is
      known about the feasibility of DT earlier in the course in patients with
      incurable malignant disease who are still receiving chemotherapy. OBJECTIVES: To
      assess the feasibility of DT relatively early in the disease trajectory (primary
      endpoint) and the effect on death acceptance, distress, symptoms, quality of
      life, peacefulness, and advanced care planning (secondary outcome endpoint).
      METHODS: Stage IV colorectal cancer patients who progressed on first-line
      chemotherapy were enrolled. Patients received DT over 2 visits and had outcome
      measures assessed pre-DT, immediately post-DT and 1 month post-DT. RESULTS: 15 of
      17 patients (88%) who were approached enrolled in the study. Most of the patients
      who completed DT reported being satisfied and felt it was helpful, that it
      increased their sense of meaning, that it would be helpful to their family, and
      that it increased their sense of dignity, their sense of purpose, and their will
      to live. LIMITATIONS: This is a small study that lacks power for statistical
      significance of findings. There is no control group for comparison. CONCLUSIONS:
      DT is a highly feasible, satisfying, and meaningful intervention for advanced
      colorectal cancer patients who are receiving chemotherapy earlier in the course
      of their and may result in an understanding of disease and goals of care at the
      end of life. Larger feasibility and exploratory studies are warranted in advanced
      cancer patients.

PMID- 25866896
TI  - Long noncoding ribonucleic acid specific for distant metastasis of gastric cancer
      is associated with TRIM16 expression and facilitates tumor cell invasion in
      vitro.
AB  - BACKGROUND AND AIM: Increasing evidence has indicated that long noncoding
      ribonucleic acids (lncRNAs) play a major role in cancers. Although certain
      lncRNAs has been reported to play a role in gastric cancer (GC), specific lncRNAs
      involved in distant metastasis of GC remain unknown. METHODS: Differentially
      expressed mRNAs and lncRNAs between stage IV and non-stage IV GC were obtained by
      microarray. Gene ontology and pathway analysis were used to study functions of
      differential mRNAs. Algorithms were used to predict potential gene targets of cis
      or trans-acting lncRNAs. Network analysis was performed to analyze each pair of
      gene-lncRNA, gene-gene, or lncRNA-lncRNA interactions. Expression of lncRNA
      special for distant metastasis of GC (SDMGC) and target gene TRIM16 were tested
      in GC tissues and cell lines. RNAi and overexpression were used to observe the
      biological functions of SDMGC and TRIM16 on GC cells. RESULTS: 502 mRNAs and 440
      lncRNAs were found to be differentially expressed. 74 gene ontology terms and 38
      pathways were associated with the dysregulated transcripts. Fourteen core factors
      were determined by network analysis. Expression of SDMGC and TRIM16 was
      upregulated in the distant metastasis tissues, compared with primary GC tissues,
      which were positive correlation. Silencing of SDMGC or TRIM16 was demonstrated to
      decrease cell invasion and migration, while upregulated of SDMGC or TRIM16 could
      promote cell invasion and migration. However, little effect on proliferation,
      cell cycle, colony formation, and apoptosis was found. CONCLUSIONS: SDMGC is
      obviously upregulated in stage IV GC and may represent a new marker and
      therapeutic target for GC treatment.

PMID- 25866897
TI  - Short-term fish reproduction assays with methyl tertiary butyl ether with
      zebrafish and fathead minnow: Implications for evaluation of potential for
      endocrine activity.
AB  - The authors report on short-term fish reproduction assays in zebrafish and
      fathead minnow conducted to examine the potential for methyl tertiary butyl ether
      (MTBE) to cause effects on the endocrine system. Both studies were performed
      under good laboratory practice and in accordance with Organisation for Economic
      Co-operation and Development and US Environmental Protection Agency test
      guidelines. The results of the first study demonstrated that exposure to a high
      test concentration (147 mg/L) of MTBE impaired reproductive output of female
      zebrafish, evident by a reduction in fecundity. Based on the endpoints evaluated
      in the present study however, there was no supporting evidence to indicate that
      this effect was caused by disruption of or interaction with the endocrine system.
      In the second study, fathead minnows exposed to a wider but lower range of test
      concentrations showed no effects on any reproductive parameter of male or female
      fish, at the maximum recommended testing concentration of 100 mg/L (62 mg/L
      measured). The results of these 2 guideline studies indicate that MTBE does not
      interact with the hypothalamic-pituitary-gonadal axis of zebrafish or fathead
      minnow.

PMID- 25866898
TI  - Development of a Hyperglycosylated IFN Alfacon-1 (CIFN): Toward Bimonthly or
      Monthly Dosing for Antiviral Therapies.
AB  - Type 1 interferons (IFNs) have been shown to be efficacious against hepatitis C
      virus (HCV), hepatitis B virus (HBV), and some cancers with a significant
      drawback of short drug exposure. We have significantly improved the
      pharmacokinetic (PK) of consensus interferon (CIFN) by glycoengineering. We
      generated AL-624 by introducing 4 glycosylation sites. AL-624 was expressed,
      purified, and fractionated to yield 2-Gly, 3-Gly, and 4-Gly. In a rat PK study,
      AL-624 4-Gly exhibited a 6-fold increase of area under curve (AUC) and more than
      an 11-fold increase in time to half life (T1/2) over CIFN, suggesting the
      potential for weekly dosing (QW). In Yellow fever virus hamster model, QW of 4
      Gly achieved similar efficacy to daily dosing (QD) CIFN and QW Peg-IFN-alpha-2a
      in overall survival rate and reduction of alanine aminotransferase (ALT) level.
      Further refinement resulted in development of AL-683 by addition of external
      glycosylation sites and its mouse homologue. AL-683 maintains undiminished
      biological potency in HCV replicon. In mouse PK/pharmacodynamic (PD) studies, AL
      683 homologue has a ~37-fold improvement in T1/2 and a ~33-fold improvement in
      AUC when compared with the unglycosylated mouse IFN-alpha-1. Significantly
      improved PD responses were also observed. The significant improvement of AL-683
      PK over AL-624 suggests a bimonthly dosing regimen for AL-683. The possibility
      for once-a-month dosing could be realized by further optimization of
      manufacturing conditions. 

PMID- 25866899
TI  - Stable [48]-, [50]-, and [52]dodecaphyrins(1.1.0.1.1.0.1.1.0.1.1.0): the largest
      Huckel aromatic molecules.
AB  - [52]Dodecaphyrin(1.1.0.1.1.0.1.1.0.1.1.0) was quantitatively oxidized with 2,3
      dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) to the corresponding
      [50]dodecaphyrin. Further oxidation of [50]dodecaphyrin with MnO2 quantitatively
      afforded [48]dodecaphyrin. Of the three, [50]dodecaphyrin showed Huckel aromatic
      character as the largest aromatic molecule reported to date. Protonation of
      [50]dodecaphyrin with methanesulfonic acid (MSA) led to the formation of a planar
      tetraprotonated species that displayed a sharp and intense Soret-like band at 906
      nm with epsilon=6.5*10(5) M(-1) cm(-1) and Q-band-like bands at 1346 and 1600 nm.

PMID- 25866900
TI  - Amniocentesis for threatened preterm labor with intact membranes and the impact
      on adverse outcome in infants born at 22 to 28 weeks of gestation.
AB  - BACKGROUND: It remains unclear whether performing amniocentesis to detect intra
      amniotic infection is useful for improving neonatal outcomes. AIMS: To determine
      the efficacy of amniocentesis on the neonatal outcomes in women exhibiting
      threatened preterm labor and intact membranes. STUDY DESIGN: Retrospective cohort
      study SUBJECTS: A total of 174 women with threatened preterm labor and intact
      membranes at 22 to 33 weeks of gestation. Women with obvious clinical
      chorioamnionitis, multifetal pregnancy and/or major anomalies were excluded.
      OUTCOME MEASURES: Neonatal short- and long-term outcomes RESULTS: Sixty-seven
      women underwent amniocentesis (Tap group), while the remaining 107 did not. The
      prevalence of a positive Gram stain or a positive culture result was 10% in the
      Tap group. The overall outcomes were not statistically different between the two
      groups, with the exception of borderline significance (p=0.052) in long-term
      outcomes, favoring the Tap group. We performed a subgroup analysis focusing on
      infants born at 22-28 weeks of gestation. Consequently, the Tap group had better
      neonatal outcomes than the no-Tap group with respect to both short-term (OR 0.19,
      95%CI 0.07-0.55) and long-term (OR 0.15, 0.05-0.46) outcomes. A multivariate
      analysis revealed that after adjusting confounding factors, the gestational age
      at delivery (OR 0.4, 0.3-0.7) and amniocentesis (OR 0.1, 0.02-0.3) remained
      significantly different. CONCLUSIONS: Amniocentesis is useful for improving
      neonatal outcomes in infants born at 22-28 weeks of gestation to women exhibiting
      preterm labor and intact membranes.

PMID- 25866901
TI  - The mesenteric lymph duct cannulated rat model: application to the assessment of
      intestinal lymphatic drug transport.
AB  - The intestinal lymphatic system plays key roles in fluid transport, lipid
      absorption and immune function. Lymph flows directly from the small intestine via
      a series of lymphatic vessels and nodes that converge at the superior mesenteric
      lymph duct. Cannulation of the mesenteric lymph duct thus enables the collection
      of mesenteric lymph flowing from the intestine. Mesenteric lymph consists of a
      cellular fraction of immune cells (99% lymphocytes), aqueous fraction (fluid,
      peptides and proteins such as cytokines and gut hormones) and lipoprotein
      fraction (lipids, lipophilic molecules and apo-proteins). The mesenteric lymph
      duct cannulation model can therefore be used to measure the concentration and
      rate of transport of a range of factors from the intestine via the lymphatic
      system. Changes to these factors in response to different challenges (e.g.,
      diets, antigens, drugs) and in disease (e.g., inflammatory bowel disease, HIV,
      diabetes) can also be determined. An area of expanding interest is the role of
      lymphatic transport in the absorption of orally administered lipophilic drugs and
      prodrugs that associate with intestinal lipid absorption pathways. Here we
      describe, in detail, a mesenteric lymph duct cannulated rat model which enables
      evaluation of the rate and extent of lipid and drug transport via the lymphatic
      system for several hours following intestinal delivery. The method is easily
      adaptable to the measurement of other parameters in lymph. We provide detailed
      descriptions of the difficulties that may be encountered when establishing this
      complex surgical method, as well as representative data from failed and
      successful experiments to provide instruction on how to confirm experimental
      success and interpret the data obtained. 

PMID- 25866903
TI  - Archaeal viruses multiply: temporal screening in a solar saltern.
AB  - Hypersaline environments around the world are dominated by archaea and their
      viruses. To date, very little is known about these viruses and their interaction
      with the host strains when compared to bacterial and eukaryotic viruses. We
      performed the first culture-dependent temporal screening of haloarchaeal viruses
      and their hosts in the saltern of Samut Sakhon, Thailand, during two subsequent
      years (2009, 2010). Altogether we obtained 36 haloarchaeal virus isolates and 36
      archaeal strains, significantly increasing the number of known archaeal virus
      isolates. Interestingly, the morphological distribution of our temporal isolates
      (head-tailed, pleomorphic, and icosahedral membrane-containing viruses) was
      similar to the outcome of our previous spatial survey supporting the observations
      of a global resemblance of halophilic microorganisms and their viruses.
      Myoviruses represented the most abundant virus morphotype with strikingly broad
      host ranges. The other viral morphotypes (siphoviruses, as well as pleomorphic
      and icosahedral internal membrane-containing viruses) were more host-specific. We
      also identified a group of Halorubrum strains highly susceptible to numerous
      different viruses (up to 26). This high virus sensitivity, the abundance of broad
      host range viruses, and the maintenance of infectivity over a period of one year
      suggest constant interplay of halophilic microorganisms and their viruses within
      an extreme environment. 

PMID- 25866905
TI  - The impact of screening-test negative samples not enumerated by MPN.
AB  - In microbiological surveys, false negative results in detection tests precluding
      the enumeration by MPN may occur. The objective of this study was to illustrate
      the impact of screening test failure on the probability distribution of
      Salmonella concentrations in pork using a Bayesian method. A total of 276 swab
      samples in four slaughter steps (69 samples in each slaughter step: after
      dehairing, after singeing, after evisceration, and before chilling) were screened
      for Salmonella and enumerated by the MPN method. Salmonella contamination data
      were fitted to a lognormal distribution by using a Bayesian model that uses the
      number of positive tubes at each dilution in an MPN analysis to estimate the
      parameters of the concentration distribution. With Salmonella paired data, three
      data sets were used for each slaughter step: one that includes the positives in
      the screening test only, a second one that includes false negative results from
      the screening, and a third that considers the entire data set. The relative
      sensitivity of the screening test was also calculated assuming as gold standard
      samples with confirmed Salmonella. Salmonella was confirmed by a reference
      laboratory in 29 samples either by screening or MPN method. The relative
      sensitivity of the screening test was 69% (CI 95%: 52%-85%). The data set that
      included enumerations from screen-negative samples (false negative results)
      tended to have higher MU and smaller sigma in comparison with the data set that
      discards false negative results, suggesting that the lack of sensitivity of the
      screening test affects the distribution that describes the contamination across
      the population. Numerous surveys on fitting distribution methods of microbial
      censored data have been published and discuss source of bias due to fitting
      method. Results of this survey contribute with that discussion by illustrating
      another possible source of bias due to failure of the screening methods preceding
      the MPN.

PMID- 25866902
TI  - The role of Merkel cell polyomavirus and other human polyomaviruses in emerging
      hallmarks of cancer.
AB  - Polyomaviruses are non-enveloped, dsDNA viruses that are common in mammals,
      including humans. All polyomaviruses encode the large T-antigen and small t
      antigen proteins that share conserved functional domains, comprising binding
      motifs for the tumor suppressors pRb and p53, and for protein phosphatase 2A,
      respectively. At present, 13 different human polyomaviruses are known, and for
      some of them their large T-antigen and small t-antigen have been shown to possess
      oncogenic properties in cell culture and animal models, while similar functions
      are assumed for the large T- and small t-antigen of other human polyomaviruses.
      However, so far the Merkel cell polyomavirus seems to be the only human
      polyomavirus associated with cancer. The large T- and small t-antigen exert their
      tumorigenic effects through classical hallmarks of cancer: inhibiting tumor
      suppressors, activating tumor promoters, preventing apoptosis, inducing
      angiogenesis and stimulating metastasis. This review elaborates on the putative
      roles of human polyomaviruses in some of the emerging hallmarks of cancer. The
      reciprocal interactions between human polyomaviruses and the immune system
      response are discussed, a plausible role of polyomavirus-encoded and polyomavirus
      induced microRNA in cancer is described, and the effect of polyomaviruses on
      energy homeostasis and exosomes is explored. Therapeutic strategies against these
      emerging hallmarks of cancer are also suggested. 

PMID- 25866906
TI  - The application of non-Saccharomyces yeast in fermentations with limited aeration
      as a strategy for the production of wine with reduced alcohol content.
AB  - High alcohol concentrations reduce the complexity of wine sensory properties. In
      addition, health and economic drivers have the wine industry actively seeking
      technologies that facilitate the production of wines with lower alcohol content.
      One of the simplest approaches to achieve this aim would be the use of wine yeast
      strains which are less efficient at transforming grape sugars into ethanol,
      however commercially available wine yeasts produce very similar ethanol yields.
      Non-conventional yeast, in particular non-Saccharomyces species, have shown
      potential for producing wines with lower alcohol content. These yeasts are
      naturally present in the early stages of fermentation but in general are not
      capable of completing alcoholic fermentation. We have evaluated 48 non
      Saccharomyces isolates to identify strains that, with limited aeration and in
      sequential inoculation regimes with S. cerevisiae, could be used for the
      production of wine with lower ethanol concentration. Two of these, Torulaspora
      delbrueckii AWRI1152 and Zygosaccharomyces bailii AWRI1578, enabled the
      production of wine with reduced ethanol concentration under limited aerobic
      conditions. Depending on the aeration regime T. delbrueckii AWRI1152 and Z.
      bailii AWRI1578 showed a reduction in ethanol concentration of 1.5% (v/v) and
      2.0% (v/v) respectively, compared to the S. cerevisiae anaerobic control. 

PMID- 25866904
TI  - Insect-specific flaviviruses: a systematic review of their discovery, host range,
      mode of transmission, superinfection exclusion potential and genomic
      organization.
AB  - There has been a dramatic increase in the number of insect-specific flaviviruses
      (ISFs) discovered in the last decade. Historically, these viruses have generated
      limited interest due to their inability to infect vertebrate cells. This
      viewpoint has changed in recent years because some ISFs have been shown to
      enhance or suppress the replication of medically important flaviviruses in co
      infected mosquito cells. Additionally, comparative studies between ISFs and
      medically important flaviviruses can provide a unique perspective as to why some
      flaviviruses possess the ability to infect and cause devastating disease in
      humans while others do not. ISFs have been isolated exclusively from mosquitoes
      in nature but the detection of ISF-like sequences in sandflies and chironomids
      indicates that they may also infect other dipterans. ISFs can be divided into two
      distinct phylogenetic groups. The first group currently consists of approximately
      12 viruses and includes cell fusing agent virus, Kamiti River virus and Culex
      flavivirus. These viruses are phylogenetically distinct from all other known
      flaviviruses. The second group, which is apparently not monophyletic, currently
      consists of nine viruses and includes Chaoyang virus, Nounane virus and Lammi
      virus. These viruses phylogenetically affiliate with mosquito/vertebrate
      flaviviruses despite their apparent insect-restricted phenotype. This article
      provides a review of the discovery, host range, mode of transmission,
      superinfection exclusion ability and genomic organization of ISFs. This article
      also attempts to clarify the ISF nomenclature because some of these viruses have
      been assigned more than one name due to their simultaneous discoveries by
      independent research groups. 

PMID- 25866907
TI  - Development and validation of a surrogate strain cocktail to evaluate
      bactericidal effects of pressure on verotoxigenic Escherichia coli.
AB  - Many strains of verotoxigenic Escherichia coli (VTEC) are highly resistant to
      pressure. To facilitate future studies to improve the elimination of VTEC by
      pressure processing of food, this study developed and validated a cocktail of non
      pathogenic strains of E. coli with equal or higher resistance to pressure when
      compared to pressure resistant strains of VTEC. Strains of E. coli obtained from
      a beef processing plant were screened for their resistance to heat and pressure.
      Treatments were carried out in LB broth. Cell counts of 3 out of 16 strains were
      reduced by 5-6 log (cfu/mL) after 30 min at 60  degrees C, and cell counts of 10
      out of 16 strains were reduced by 5-6 log (cfu/mL) after 30 min at 40  degrees C
      and 400 MPa. All highly heat resistant strains were also pressure resistant but
      not all pressure resistant strains were also heat resistant. Pressure resistant
      and -sensitive strains of E. coli were treated in presence of 0 or 2% NaCl and at
      3, 20, or 40  degrees C. The effect of these parameters on the lethality of
      pressure treatments was comparable for all strains. The addition of 2% NaCl did
      not increase pressure resistance. The bactericidal effect of treatments at 3 and
      20  degrees C and 600 MPa was comparable but inactivation of E. coli was faster
      at 40  degrees C and 600 MPa. The resistance to treatment with 600 MPa at 20 
      degrees C of a cocktail of 5 non-pathogenic strains of E. coli was compared to a
      5 strain cocktail of pressure resistant VTEC. Treatments were performed in ground
      beef containing 15% fat. Survival and sublethal injury of the two cocktails was
      comparable; cell counts of beef inoculated with either cocktail were reduced by
      about 4 log (cfu/mL) after 30 min of treatment. In conclusion, this study
      validated a cocktail of non-pathogenic strains of E. coli for use as surrogate
      organisms in studies on the elimination of E. coli by pressure.

PMID- 25866908
TI  - Benefits and drawbacks of open partial horizontal laryngectomies, Part B:
      Intermediate and selected advanced stage laryngeal carcinoma.
AB  - BACKGROUND: Cancer of the larynx in the intermediate/advanced stage still
      presents a major challenge in terms of controlling the disease and preserving the
      organ. Among therapeutic options, open partial horizontal laryngectomy is
      proposed as a function-sparing surgical technique. METHODS: We analyzed the
      clinical outcomes of 555 patients with laryngeal cancer staged pT3 to pT4a who
      underwent open partial horizontal laryngectomy. RESULTS: Five-year overall
      survival (OS), disease-free survival (DFS), locoregional control, local control,
      laryngectomy-free survival, and laryngeal function preservation rates were 84.6%,
      84.2%, 86.3%, 90.6%, 93.3%, and 91.2%, respectively. DFS, locoregional control,
      and laryngeal function preservation rates were significantly affected by pT4a
      staging (68.1%, 71.7%, and 78.0%, respectively), whereas pN+ influenced only DFS
      (<=72.6%) and locoregional control (<=79.6%). CONCLUSIONS: Open partial
      horizontal laryngectomy with a modular approach can be considered effective in
      terms of prognostic and functional results in intermediate-stage and selected
      advanced-stage laryngeal cancers, even with subglottic extension. (c) 2015 Wiley
      Periodicals, Inc. Head Neck 38: E649-E657, 2016.

PMID- 25866909
TI  - Impedimetric DNA-biosensor for the study of dopamine induces DNA damage and
      investigation of inhibitory and repair effects of some antioxidants.
AB  - A simple and inexpensive methodology was used to develop a new method in order to
      inspect the DNA damage due to dopamine and some ionic metals. In addition, the
      inhibitory and repair effects of some antioxidant such as glutathione and
      ascorbic acid were studied and compared with each other using electrochemical
      impedance spectroscopy (EIS) and differential pulse voltammetry (DPV). In this
      work a pencil graphite electrode (PGE) was modified with multiwall carbon
      nanotubes (MWCNTs) and chitosan (CHIT), then it was decorated with a ds-DNA (ds
      DNA/CHIT-MWCNTs/PGE). Due to interaction of ds-DNA and the damaging agents
      (dopamine+metallic ions), electrochemical and spectroscopy properties of ds-DNA
      at the surface of the modified electrode was changed, and these changes are
      followed with EIS and DPV methods. Our study showed that dopamine, Cu(II) and
      Fe(III) alone could not destroy DNA, but dopamine + Cu(II) and dopamine + Fe(III)
      can damage DNA. In addition, the ability of dopamine-Cu(II) was greater than
      dopamine-Fe(III). Moreover, some antioxidant such as glutathione and ascorbic
      acid can overcome and/or minimize the influence of these damaging interactions.

PMID- 25866910
TI  - U.S. research regulations: do they reflect the views of the people they claim to
      protect?

PMID- 25866911
TI  - Interleukin-6 as a prognostic marker in dogs in an intensive care unit.
AB  - BACKGROUND: Interleukin-6 (IL-6) is involved in the acute phase reaction during
      inflammatory disease, including septicemia and the inflammatory response syndrome
      (SIRS). In people, IL-6 has been studied as a prognostic marker in intensive care
      medicine, where nonsurvivors had significantly higher IL-6 concentrations than
      survivors. OBJECTIVES: The objective of the study was to investigate the
      prognostic value of IL-6 in dogs admitted to the intensive care unit based on
      sensitivity and specificity. METHODS: Dogs suffering from different severe
      diseases treated in the intensive care unit were divided into 2 groups of
      survivors and nonsurvivors. Serum IL-6 concentrations were measured with a canine
      specific ELISA (enzyme-linked immunosorbent assay) kit. RESULTS: Sixty-nine dogs
      were included in the study, including 20 survivors, 9 nonsurvivors, and 40
      control dogs. In the control group, IL-6 serum concentrations were below the
      detection level (0 pg/mL). In the group of nonsurviving dogs, IL-6 ranged from 45
      4656 pg/mL (median 1398 pg/mL). The surviving dogs had a range of 0-405 pg/mL
      (median 84.5 pg/mL). The mean IL-6 concentration was significantly higher (P <
      .001) in nonsurvivors than in survivors. Using a cutoff of 400 pg/mL, a
      sensitivity of 90% and specificity of 95% were determined. CONCLUSIONS: The
      results of this study suggest that IL-6 is a useful prognostic marker for canine
      critical care patients with acute internal disease.

PMID- 25866912
TI  - Spectrin-ankyrin interaction mechanics: A key force balance factor in the red
      blood cell membrane skeleton.
AB  - As major components of red blood cell (RBC) cytoskeleton, spectrin and F-actin
      form a network that covers the entire cytoplasmic surface of the plasma membrane.
      The cross-linked two layered structure, called the membrane skeleton, keeps the
      structural integrity of RBC under drastically changing mechanical environment
      during circulation. We performed force spectroscopy experiments on the atomic
      force microscope (AFM) as a means to clarify the mechanical characteristics of
      spectrin-ankyrin interaction, a key factor in the force balance of the RBC
      cytoskeletal structure. An AFM tip was functionalized with ANK1-62k and used to
      probe spectrin crosslinked to mica surface. A force spectroscopy study gave a
      mean unbinding force of ~30 pN under our experimental conditions. Two energy
      barriers were identified in the unbinding process. The result was related to the
      well-known flexibility of spectrin tetramer and participation of ankyrin 1
      spectrin interaction in the overall balance of membrane skeleton dynamics.

PMID- 25866913
TI  - Ribosomal Protein P2 from apicomplexan parasite Toxoplasma gondii is
      intrinsically a molten globule.
AB  - Toxoplasma gondii is an apicomplexan parasite, which causes toxoplasmosis.
      Toxoplasma P2 (TgP2) is a ribosomal protein and exists as supramolecular assembly
      with other proteins in the ribosome. It is also shown that TgP2 is involved in
      some extra ribosomal functions. However, till date the protein has evaded
      structural characterization by any of the known techniques. In this background,
      we report here a systematic study using a variety of biophysical techniques and
      NMR, under different conditions of pH and temperature, and deduce that TgP2
      consists of only helices and unstructured regions, is a monomer at low pH but
      forms multimers at higher pH, and has intrinsically a molten globule structure.
      The C-terminal half is flexible and the helices are concentrated in the N
      terminal half of the chain. The dynamism inherent to the molten globule structure
      may have functional implications for its extra-ribosomal functions. which is
      contrast to that of human P2. 

PMID- 25866914
TI  - Methods for characterizing the co-development of biofilm and habitat
      heterogeneity.
AB  - Biofilms are surface-attached microbial communities that have complex structures
      and produce significant spatial heterogeneities. Biofilm development is strongly
      regulated by the surrounding flow and nutritional environment. Biofilm growth
      also increases the heterogeneity of the local microenvironment by generating
      complex flow fields and solute transport patterns. To investigate the development
      of heterogeneity in biofilms and interactions between biofilms and their local
      micro-habitat, we grew mono-species biofilms of Pseudomonas aeruginosa and dual
      species biofilms of P. aeruginosa and Escherichia coli under nutritional
      gradients in a microfluidic flow cell. We provide detailed protocols for creating
      nutrient gradients within the flow cell and for growing and visualizing biofilm
      development under these conditions. We also present protocols for a series of
      optical methods to quantify spatial patterns in biofilm structure, flow
      distributions over biofilms, and mass transport around and within biofilm
      colonies. These methods support comprehensive investigations of the co
      development of biofilm and habitat heterogeneity. 

PMID- 25866915
TI  - Systematic study of the reaction kinetics for HMX.
AB  - The reaction process of octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) in
      wide temperature and pressure ranges is simulated by molecular dynamics. A set of
      postprocessing programs is written to evaluate the intermediate molecules and
      chemical reactions. On the basis of these evaluations, the reaction rates,
      reactive Hugoniot curves, and detonation wave profile are calculated. The
      detonation velocity and detonation pressure are determined as 9984 m/s and
      38.3349 GPa, in agreement with the experimental results, 9110 m/s and 39.5 GPa.
      The width of the reaction zone is 10 MUm, and the main products are N2, H2O, and
      CO2. We find some molecules play an important role in intermediate reactions but
      are not exhibited in final products, such as N2O2, N2O5, and C3H3N3. 

PMID- 25866916
TI  - Simple polyacrylamide-based multiwell stiffness assay for the study of stiffness
      dependent cell responses.
AB  - Currently, most of the in vitro cell research is performed on rigid tissue
      culture polystyrene (~1 GPa), while most cells in the body are attached to a
      matrix that is elastic and much softer (0.1-100 kPa). Since such stiffness
      mismatch greatly affects cell responses, there is a strong interest in developing
      hydrogel materials that span a wide range of stiffness to serve as cell
      substrates. Polyacrylamide gels, which are inexpensive and cover the stiffness
      range of all soft tissues in the body, are the hydrogel of choice for many
      research groups. However, polyacrylamide gel preparation is lengthy, tedious, and
      only suitable for small batches. Here, we describe an assay which by utilizing a
      permanent flexible plastic film as a structural support for the gels, enables the
      preparation of polyacrylamide gels in a multiwell plate format. The technique is
      faster, more efficient, and less costly than current methods and permits the
      preparation of gels of custom sizes not otherwise available. As it doesn't
      require any specialized equipment, the method could be easily adopted by any
      research laboratory and would be particularly useful in research focused on
      understanding stiffness-dependent cell responses.

PMID- 25866917
TI  - Developmental anatomy of the liver from computerized three-dimensional
      reconstructions of four human embryos (from Carnegie stage 14 to 23).
AB  - BACKGROUND & AIM: Some aspects of human embryogenesis and organogenesis remain
      unclear, especially concerning the development of the liver and its vasculature.
      The purpose of this study was to investigate, from a descriptive standpoint, the
      evolutionary morphogenesis of the human liver and its vasculature by computerized
      three-dimensional reconstructions of human embryos. MATERIAL & METHODS: Serial
      histological sections of four human embryos at successive stages of development
      belonging to three prestigious French historical collections were digitized and
      reconstructed in 3D using software commonly used in medical radiology. Manual
      segmentation of the hepatic anatomical regions of interest was performed section
      by section. RESULTS: In this study, human liver organogenesis was examined at
      Carnegie stages 14, 18, 21 and 23. Using a descriptive and an analytical method,
      we showed that these stages correspond to the implementation of the large hepatic
      vascular patterns (the portal system, the hepatic artery and the hepatic venous
      system) and the biliary system. CONCLUSION: To our knowledge, our work is the
      first descriptive morphological study using 3D computerized reconstructions from
      serial histological sections of the embryonic development of the human liver
      between Carnegie stages 14 and 23.

PMID- 25866918
TI  - Investigating the biometric and physicochemical characteristics of freshly
      harvested Pacific white shrimp (Litopenaeus vannamei): a comparative approach.
AB  - BACKGROUND: The practicality of biometrics of seafood cannot be overemphasized,
      particularly for competent authorities of the shrimp industry. However, there is
      a paucity of relevant literature on the relationship between biometric and
      physicochemical indices of freshly harvested shrimp. This work therefore
      investigated the relationship between biometric (standard length (SL), total
      weight (TW) and condition factor (CF)) and physicochemical (moisture content, pH,
      titratable acidity, water activity, water retention index, colour values and
      fracturability) characteristics of freshly harvested Pacific white shrimp
      (Litopenaeus vannamei) obtained from three different farms. The relationships
      between these parameters were determined using correlation and regression
      analyses. RESULTS: No significant correlation (P > 0.05) was found between the
      biometric and physicochemical indices of the sampled L. vannamei specimens.
      Possibly the lack of post-mortem and physical change(s) at day of harvest
      together with the absence of temporal variable may have collectively limited the
      degree of any significant correlation between biometric and physicochemical data
      points measured in this study. Although the TWs of freshly harvested L. vannamei
      shrimp resembled (P > 0.05), SL and CF differed significantly (P < 0.05) with
      minimal explained variance. Moreover, some biometric and physicochemical
      variables were independently correlated (P < 0.05). CONCLUSION: Data indicated
      that no significant correlation existed between biometric and physicochemical
      characteristics of freshly harvested L. vannamei shrimp. Across the farms
      studied, however, the biometric data were comparable. To best knowledge, this is
      the first study to investigate the biometric and physicochemical properties of
      freshly harvested shrimp using a comparative approach, which is also applicable
      to other economically important aquaculture species. Overall, this work provides
      useful information for competent authorities/stakeholders of the fishery industry
      and serves as a baseline for preservative treatments.

PMID- 25866919
TI  - The continuing evolution of pediatric emergency care.

PMID- 25866920
TI  - Function and pathological implications of exon junction complex factor Y14.
AB  - Eukaryotic mRNA biogenesis involves a series of interconnected steps, including
      nuclear pre-mRNA processing, mRNA export, and surveillance. The exon-junction
      complex (EJC) is deposited on newly spliced mRNAs and coordinates several
      downstream steps of mRNA biogenesis. The EJC core protein, Y14, functions with
      its partners in nonsense-mediated mRNA decay and translational enhancement. Y14
      plays additional roles in mRNA metabolism, some of which are independent of the
      EJC, and it is also involved in other cellular processes. Genetic mutations or
      aberrant expression of Y14 results in physiological abnormality and may cause
      disease. Therefore, it is important to understand the various functions of Y14
      and its physiological and pathological roles. 

PMID- 25866922
TI  - Estimating safety performance trends over time for treatments at intersections in
      Florida.
AB  - Researchers have put great efforts in quantifying Crash Modification Factors
      (CMFs) for diversified treatment types. In the Highway Safety Manual (HSM), CMFs
      have been identified to predict safety effectiveness of converting a stop
      controlled to a signal-controlled intersection (signalization) and installing Red
      Light Running Cameras (RLCs). Previous studies showed that both signalization and
      adding RLCs reduced angle crashes but increased rear-end crashes. However, some
      studies showed that CMFs varied over time after the treatment was implemented.
      Thus, the objective of this study is to investigate trends of CMFs for the
      signalization and adding RLCs over time. CMFs for the two treatments were
      measured in each month and 90-day moving windows respectively. The ARMA time
      series model was applied to predict trends of CMFs over time based on monthly
      variations in CMFs. The results of the signalization show that the CMFs for rear
      end crashes were lower at the early phase after the signalization but gradually
      increased from the 9th month. On the other hand, the CMFs for angle crashes were
      higher at the early phase after adding RLCs but decreased after the 9th month and
      then became stable. It was also found that the CMFs for total and fatal/injury
      crashes after adding RLCs in the first 18 months were significantly greater than
      the CMFs in the following 18 months. This indicates that there was a lag effect
      of the treatments on safety performance. The results of the ARMA model show that
      the model can better predict trends of the CMFs for the signalization and adding
      RLCs when the CMFs are calculated in 90-day moving windows compared to the CMFs
      calculated in each month. In particular, the ARMA model predicted a significant
      safety effect of the signalization on reducing angle and left-turn crashes in the
      long term. Thus, it is recommended that the safety effects of the treatment be
      assessed using the ARMA model based on trends of CMFs in the long term after the
      implementation of the treatment. 

PMID- 25866921
TI  - Impact of oxidative stress on exercising skeletal muscle.
AB  - It is well established that muscle contractions during exercise lead to elevated
      levels of reactive oxygen species (ROS) in skeletal muscle. These highly reactive
      molecules have many deleterious effects, such as a reduction of force generation
      and increased muscle atrophy. Since the discovery of exercise-induced oxidative
      stress several decades ago, evidence has accumulated that ROS produced during
      exercise also have positive effects by influencing cellular processes that lead
      to increased expression of antioxidants. These molecules are particularly
      elevated in regularly exercising muscle to prevent the negative effects of ROS by
      neutralizing the free radicals. In addition, ROS also seem to be involved in the
      exercise-induced adaptation of the muscle phenotype. This review provides an
      overview of the evidences to date on the effects of ROS in exercising muscle.
      These aspects include the sources of ROS, their positive and negative cellular
      effects, the role of antioxidants, and the present evidence on ROS-dependent
      adaptations of muscle cells in response to physical exercise. 

PMID- 25866923
TI  - Identification of molecular determinants of primary and metastatic tumour re
      initiation in breast cancer.
AB  - Through in vivo selection of multiple ER-negative human breast cancer populations
      for enhanced tumour-forming capacity, we have derived subpopulations that
      generate tumours more efficiently than their parental populations at low cell
      numbers. Tumorigenic-enriched subpopulations exhibited increased expression of
      LAMA4, FOXQ1 and NAP1L3-genes that are also expressed at greater levels by
      independently derived metastatic subpopulations. These genes promote metastatic
      efficiency. FOXQ1 promotes LAMA4 expression, and LAMA4 enhances clonal expansion
      following substratum detachment in vitro, tumour re-initiation in multiple
      organs, and disseminated metastatic cell proliferation and colonization. The
      promotion of cancer cell proliferation and tumour re-initiation by LAMA4 requires
      beta1-integrin. Increased LAMA4 expression marks the transition of human pre
      malignant breast lesions to malignant carcinomas, and tumoral LAMA4
      overexpression predicts reduced relapse-free survival in ER-negative patients.
      Our findings reveal common features that govern primary and metastatic tumour re
      initiation and identify a key molecular determinant of these processes.

PMID- 25866924
TI  - Kinetochore components are required for central spindle assembly.
AB  - A critical structure poised to coordinate chromosome segregation with division
      plane specification is the central spindle that forms between separating
      chromosomes after anaphase onset. The central spindle acts as a signalling centre
      that concentrates proteins essential for division plane specification and
      contractile ring constriction. However, the molecular mechanisms that control the
      initial stages of central spindle assembly remain elusive. Using Caenorhabditis
      elegans zygotes, we found that the microtubule-bundling protein SPD-1(PRC1) and
      the motor ZEN-4(MKLP-1) are required for proper central spindle structure during
      its elongation. In contrast, we found that the kinetochore controls the
      initiation of central spindle assembly. Specifically, central spindle microtubule
      assembly is dependent on kinetochore recruitment of the scaffold protein KNL-1,
      as well as downstream partners BUB-1, HCP-1/2(CENP-F) and CLS-2(CLASP); and is
      negatively regulated by kinetochore-associated protein phosphatase 1 activity.
      This in turn promotes central spindle localization of CLS-2(CLASP) and initial
      central spindle microtubule assembly through its microtubule polymerase activity.
      Together, our results reveal an unexpected role for a conserved kinetochore
      protein network in coupling two critical events of cell division: chromosome
      segregation and cytokinesis. 

PMID- 25866925
TI  - The retrotrapezoid nucleus neurons expressing Atoh1 and Phox2b are essential for
      the respiratory response to CO2.
AB  - Maintaining constant CO2 and H(+) concentrations in the arterial blood is
      critical for life. The principal mechanism through which this is achieved in
      mammals is the respiratory chemoreflex whose circuitry is still elusive. A
      candidate element of this circuitry is the retrotrapezoid nucleus (RTN), a
      collection of neurons at the ventral medullary surface that are activated by
      increased CO2 or low pH and project to the respiratory rhythm generator. Here, we
      use intersectional genetic strategies to lesion the RTN neurons defined by Atoh1
      and Phox2b expression and to block or activate their synaptic output.
      Photostimulation of these neurons entrains the respiratory rhythm. Conversely,
      abrogating expression of Atoh1 or Phox2b or glutamatergic transmission in these
      cells curtails the phrenic nerve response to low pH in embryonic preparations and
      abolishes the respiratory chemoreflex in behaving animals. Thus, the RTN neurons
      expressing Atoh1 and Phox2b are a necessary component of the chemoreflex
      circuitry. 

PMID- 25866926
TI  - Assessing long-distance RNA sequence connectivity via RNA-templated DNA-DNA
      ligation.
AB  - Many RNAs, including pre-mRNAs and long non-coding RNAs, can be thousands of
      nucleotides long and undergo complex post-transcriptional processing. Multiple
      sites of alternative splicing within a single gene exponentially increase the
      number of possible spliced isoforms, with most human genes currently estimated to
      express at least ten. To understand the mechanisms underlying these complex
      isoform expression patterns, methods are needed that faithfully maintain long
      range exon connectivity information in individual RNA molecules. In this study,
      we describe SeqZip, a methodology that uses RNA-templated DNA-DNA ligation to
      retain and compress connectivity between distant sequences within single RNA
      molecules. Using this assay, we test proposed coordination between distant sites
      of alternative exon utilization in mouse Fn1, and we characterize the
      extraordinary exon diversity of Drosophila melanogaster Dscam1. 

PMID- 25866927
TI  - Recruitment of the default mode network during a demanding act of executive
      control.
AB  - In the human brain, a default mode or task-negative network shows reduced
      activity during many cognitive tasks and is often associated with internally
      directed processes, such as mind wandering and thoughts about the self. In
      contrast to this task-negative pattern, we show increased activity during a large
      and demanding switch in task set. Furthermore, we employ multivoxel pattern
      analysis and find that regions of interest within default mode network are
      encoding task-relevant information during task performance. Activity in this
      network may be driven by major revisions of cognitive context, whether internally
      or externally focused. 

PMID- 25866928
TI  - Reciprocal and dynamic polarization of planar cell polarity core components and
      myosin.
AB  - The Ciona notochord displays planar cell polarity (PCP), with anterior
      localization of Prickle (Pk) and Strabismus (Stbm). We report that a myosin is
      polarized anteriorly in these cells and strongly colocalizes with Stbm.
      Disruption of the actin/myosin machinery with cytochalasin or blebbistatin
      disrupts polarization of Pk and Stbm, but not of myosin complexes, suggesting a
      PCP-independent aspect of myosin localization. Wash out of cytochalasin restored
      Pk polarization, but not if done in the presence of blebbistatin, suggesting an
      active role for myosin in core PCP protein localization. On the other hand, in
      the pk mutant line, aimless, myosin polarization is disrupted in approximately
      one third of the cells, indicating a reciprocal action of core PCP signaling on
      myosin localization. Our results indicate a complex relationship between the
      actomyosin cytoskeleton and core PCP components in which myosin is not simply a
      downstream target of PCP signaling, but also required for PCP protein
      localization. 

PMID- 25866930
TI  - Ex utero electroporation and organotypic slice culture of mouse hippocampal
      tissue.
AB  - Mouse genetics offers a powerful tool determining the role of specific genes
      during development. Analyzing the resulting phenotypes by immunohistochemical and
      molecular methods provides information of potential target genes and signaling
      pathways. To further elucidate specific regulatory mechanisms requires a system
      allowing the manipulation of only a small number of cells of a specific tissue by
      either overexpression, ablation or re-introduction of specific genes and follow
      their fate during development. To achieve this ex utero electroporation of
      hippocampal structures, especially the dentate gyrus, followed by organotypic
      slice culture provides such a tool. Using this system to generate mosaic
      deletions allows determining whether the gene of interest regulates cell
      autonomously developmental processes like progenitor cell proliferation or
      neuronal differentiation. Furthermore it facilitates the rescue of phenotypes by
      re-introducing the deleted gene or its target genes. In contrast to in utero
      electroporation the ex utero approach improves the rate of successfully targeting
      deeper layers of the brain like the dentate gyrus. Overall ex utero
      electroporation and organotypic slice culture provide a potent tool to study
      regulatory mechanisms in a semi-native environment mirroring endogenous
      conditions. 

PMID- 25866929
TI  - Systematic review of interventions to reduce problematic alcohol use in men who
      have sex with men.
AB  - ISSUES: Rates of heavy drinking, alcohol problems and alcohol-related disorders
      are high among men who have sex with men (MSM) and are an important public health
      issue. Associations between heavy drinking and human immunodeficiency virus (HIV)
      acquisition among MSM also suggest that drinking may have more severe and chronic
      consequences for this population relative to others. Consequently, effective
      interventions to reduce heavy drinking and alcohol-related risk factors among MSM
      are needed. APPROACH: We conducted a systematic review of randomised controlled
      trials of interventions to reduce heavy drinking and/or alcohol-related problems
      among MSM. We searched five electronic databases, screened 3722 records and
      identified 5 studies involving 1022 participants that satisfied inclusion
      criteria, which included having: (i) incorporated a comparison condition; (ii)
      randomised participants to groups; and (iii) reported quantitative outcomes. KEY
      FINDINGS: The methodological quality of studies varied, and meta-analysis was not
      conducted because of heterogeneity in intervention approaches and outcomes.
      Studies provided preliminary support for the use of motivational
      interviewing/motivational enhancement-based interventions (MI) and hybrid MI and
      cognitive behavioural therapy treatments for heavy drinking among MSM over no
      treatment. Perhaps the most important conclusion of this review, however, is that
      well-designed, theoretically informed research focused on establishing the
      efficacy of interventions for hazardous drinking and alcohol use disorders among
      MSM is alarmingly scarce. CONCLUSIONS: Effective interventions to reduce
      hazardous drinking among MSM and prevent key alcohol-related outcomes, including
      risk for HIV transmission and health problems among HIV-positive MSM, are needed
      to mitigate health disparities in this population.

PMID- 25866931
TI  - Meat quality assessment from young goats fed for long periods with castor de
      oiled cake.
AB  - Diet can influence both the qualitative and quantitative traits of ruminant meat.
      This study evaluated the effects of castor de-oiled cake on the meat of mixed
      breed male goat kids. After 165days of diet treatment, no alterations (p>0.05)
      were observed in the in vivo performance, anatomic components, dissection and
      proximate composition of the Longissimus dorsi muscle, as well as in the color
      and pH of the carcasses. However, diet had an effect (p<0.05) on energy
      metabolites, fatty acid profile, and expression of certain proteins of the
      Longissimus dorsi muscle. To conclude, this study showed that the establishment
      of castor de-oiled cake diet for a long period to goats led to alterations in
      meat quality, without compromising its consumption qualities. 

PMID- 25866932
TI  - Sire breed effect on beef longissimus mineral concentrations and their
      relationships with carcass and palatability traits.
AB  - The objective of this study was to evaluate sire breed effect on mineral
      concentration in beef longissimus thoracis (LT) and investigate the correlations
      between beef mineral concentrations and carcass and palatability traits. Steer
      progeny (N=246) from the Germplasm Evaluation project-Cycle VIII were used in
      this study. In addition to carcass traits, LT was evaluated for mineral
      concentrations, Warner-Bratzler shear force, and palatability traits. A mixed
      linear model estimated breed effects on mineral concentrations. No significant
      sire breed (P>=0.43) or dam breed (P>=0.20) effects were identified for mineral
      concentrations. Pearson correlation coefficients were calculated among mineral
      concentrations, carcass, and sensory traits. Zinc concentration was positively
      correlated (P<=0.05) with total iron (r=0.14), heme iron (r=0.13), and magnesium
      (r=0.19). Significant (P<0.05) correlations were identified between non-heme or
      heme iron and most traits in this study. Magnesium concentration was correlated
      with all carcass and palatability traits. 

PMID- 25866934
TI  - Kinetically Inert Bispidol-Based Cu(II) Chelate for Potential Application to
      (64/67)Cu Nuclear Medicine and Diagnosis.
AB  - A family of 2,4-pyridyl-disubstituted bispidol derivatives bearing methylene
      carboxylic acid ethyl esters (L1-L3), methylene carboxylic acids (L4 and L5), or
      methylenethiophene (L6) groups were synthesized. In water, all ligands form rigid
      1:1 complexes in the presence of Zn(II) in which the bicycle adopts a chair-chair
      conformation (cis isomer), as observed by (1)H NMR and, in the case of ligand L1,
      by an X-ray diffraction crystal structure. Interestingly, addition of Zn(II) ions
      on ligand L1 induces a metal-mediated selective hydrolysis of the ethyl esters.
      This selective hydrolysis was not observed upon addition of other cations such as
      Na(+), Mg(+), and Ca(2+). Reduction of the central ketone was achieved to prevent
      ring opening via retro Diels-Alder reactions and to afford highly stable and
      water-soluble ligands (L4, L5, L6). The complexation properties of L4 and L6 were
      studied in solution, with a particular interest for ligand L4. Fast complexation
      occurs in strongly acidic media (pH = 1), with a high affinity toward Cu(II) (log
      KCuL4 = 19.2(3), pCu = 17.0 at pH 7.4, pCu = -log[Cufree], [Cu] = 1 * 10(-6) M,
      [L] = 1 * 10(-5) M) and high selectivity versus Co(II), Ni(II), and Zn(II), as
      shown by the values of the binding constants obtained from potentiometric and
      spectrophotometric titrations. Reversible redox potential with E1/2 = -430 mV (vs
      normal hydrogen electrode) was measured. The complex was found to be fairly inert
      from acid-assisted dissociation experiments in 5 M HClO4 (t1/2 = 110 d at 25 
      degrees C). 

PMID- 25866933
TI  - The effect of dietary alfalfa and flax sprouts on rabbit meat antioxidant
      content, lipid oxidation and fatty acid composition.
AB  - The aim of this study was to determine the effect of dietary supplementation with
      flax and alfalfa sprouts on fatty acid, tocopherol and phytochemical contents of
      rabbit meat. Ninety weaned New Zealand White rabbits were assigned to three
      dietary groups: standard diet (S); standard diet+20g/d of alfalfa sprouts (A);
      and standard diet+20g/d of flax sprouts (F). In the F rabbits the Longissimus
      dorsi muscle showed a higher thio-barbituric acid-reactive value and at the same
      time significantly higher values of alpha-linolenic acid, total polyunsaturated
      and n-3 fatty acids. Additionally n-3/n-6 ratio and thrombogenic indices were
      improved. The meat of A rabbits showed intermediate values of the previously
      reported examined parameters. Dietary supplementation with sprouts produced meat
      with a higher total phytoestrogen content. The addition of fresh alfalfa and flax
      sprouts to commercial feed modified the fat content, fatty acid and phytochemical
      profile of the meat, but the flax ones worsened the oxidative status of meat. 

PMID- 25866935
TI  - Detection of adrenomedullin and nitric oxide in different forms of periodontal
      disease.
AB  - BACKGROUND AND OBJECTIVE: The multifunctional molecules adrenomedullin (AM) and
      nitric oxide (NO) are both involved in the host response to microbial challenge
      during periodontal disease. Whether they coexist in periodontal inflammation and
      if equally produced in the different forms of periodontal disease has not
      previously been investigated. The aims of this study were to describe the
      locations of AM and NO in healthy and inflamed gingival tissues and to determine
      and compare their levels in the gingival crevicular fluid and saliva of patients
      with gingivitis, chronic periodontitis and aggressive periodontitis. MATERIAL AND
      METHODS: AM and inducible nitric oxide synthase (iNOS) were immunolocalized in
      clinically healthy and inflamed gingival tissue sections. The cells expressing AM
      and iNOS were characterized using immunocytochemistry with different markers for
      macrophages [cluster differentiation (CD)68 and CD14)], dendritic cells (CD83),
      neutrophils [neutrophil gelatinase-associated lipocalin (nGAL)] and natural
      killer cells (CD56). In an initial study, the levels of AM and NO were also
      measured in samples of gingival crevicular fluid and saliva obtained from
      patients with a diagnosis of gingivitis (n = 9), chronic periodontitis (n = 9)
      and aggressive periodontitis (n = 9) using an ELISA and the nitrate/nitrite (NO
      metabolites) Griess assay, respectively. RESULTS: Low levels of AM- and iNOS
      expressing cells were detected in healthy gingival tissues in comparison with
      three-fold higher levels of these cells in inflamed tissues. These cells were
      localized mainly in the epithelial layer but were also present in deeper
      connective tissue. AM and iNOS were co-localized in particular cells within
      inflamed tissues, namely CD68(+) (52%) and CD14(+) (36%) macrophages, but also in
      nGAL(+) neutrophils (16%) and CD83(+) dendritic cells (14%). Interestingly, AM
      and NO levels in saliva were both found to be higher (p < 0.01) in patients with
      aggressive periodontitis than in patients with chronic periodontitis or
      gingivitis. In contrast, in gingival crevicular fluid, the levels of NO showed
      marked differences among patients with chronic periodontitis, aggressive
      periodontitis and gingivitis (p < 0.01), and the levels of AM were higher (p <
      0.01) in both chronic and aggressive periodontitis compared with gingivitis
      alone. CONCLUSION: The data presented demonstrate a functional linkage between AM
      and NO in periodontal disease, with salivary and gingival crevicular fluid levels
      possibly associated with different forms and severities of periodontal disease.
      Exacerbated production of both AM and NO in saliva suggests their potential use
      as salivary markers of aggressive periodontitis.

PMID- 25866936
TI  - Establishment of human epithelial enteroids and colonoids from whole tissue and
      biopsy.
AB  - The epithelium of the gastrointestinal tract is constantly renewed as it turns
      over. This process is triggered by the proliferation of intestinal stem cells
      (ISCs) and progeny that progressively migrate and differentiate toward the tip of
      the villi. These processes, essential for gastrointestinal homeostasis, have been
      extensively studied using multiple approaches. Ex vivo technologies, especially
      primary cell cultures have proven to be promising for understanding intestinal
      epithelial functions. A long-term primary culture system for mouse intestinal
      crypts has been established to generate 3-dimensional epithelial organoids. These
      epithelial structures contain crypt- and villus-like domains reminiscent of
      normal gut epithelium. Commonly, termed "enteroids" when derived from small
      intestine and "colonoids" when derived from colon, they are different from
      organoids that also contain mesenchyme tissue. Additionally, these
      enteroids/colonoids continuously produce all cell types found normally within the
      intestinal epithelium. This in vitro organ-like culture system is rapidly
      becoming the new gold standard for investigation of intestinal stem cell biology
      and epithelial cell physiology. This technology has been recently transferred to
      the study of human gut. The establishment of human derived epithelial enteroids
      and colonoids from small intestine and colon has been possible through the
      utilization of specific culture media that allow their growth and maintenance
      over time. Here, we describe a method to establish a small intestinal and colon
      crypt-derived system from human whole tissue or biopsies. We emphasize the
      culture modalities that are essential for the successful growth and maintenance
      of human enteroids and colonoids. 

PMID- 25866937
TI  - Direct protein delivery to mammalian cells using cell-permeable Cys2-His2 zinc
      finger domains.
AB  - Due to their modularity and ability to be reprogrammed to recognize a wide range
      of DNA sequences, Cys2-His2 zinc-finger DNA-binding domains have emerged as
      useful tools for targeted genome engineering. Like many other DNA-binding
      proteins, zinc-fingers also possess the innate ability to cross cell membranes.
      We recently demonstrated that this intrinsic cell-permeability could be leveraged
      for intracellular protein delivery. Genetic fusion of zinc-finger motifs leads to
      efficient transport of protein and enzyme cargo into a broad range of mammalian
      cell types. Unlike other protein transduction technologies, delivery via zinc
      finger domains does not inhibit enzyme activity and leads to high levels of
      cytosolic delivery. Here a detailed step-by-step protocol is presented for the
      implementation of zinc-finger technology for protein delivery into mammalian
      cells. Key steps for achieving high levels of intracellular zinc-finger-mediated
      delivery are highlighted and strategies for maximizing the performance of this
      system are discussed. 

PMID- 25866939
TI  - Erratum.

PMID- 25866938
TI  - Effect of LSKL peptide on thrombospondin 1-mediated transforming growth factor
      beta signal activation and liver regeneration after hepatectomy in an
      experimental model.
AB  - BACKGROUND: A strategy for accelerating liver regeneration after hepatectomy
      would offer great benefits in preventing postoperative liver failure and
      improving surgical outcomes. Transforming growth factor (TGF) beta is a potent
      inhibitor of hepatocyte proliferation. Recently, thrombospondin (TSP) 1 has been
      identified as a negative regulator of liver regeneration by activation of local
      TGF-beta signals. This study aimed to clarify whether the LSKL (leucine-serine
      lysine-leucine) peptide, which inhibits TSP-1-mediated TGF-beta activation,
      promotes liver regeneration after hepatectomy in mice. METHODS: Mice were
      operated on with a 70 per cent hepatectomy or sham procedure. Operated mice
      received either LSKL peptide or normal saline intraperitoneally at abdominal
      closure and 6 h after hepatectomy. Perioperative plasma TSP-1 levels were
      measured by enzyme-linked immunosorbent assay in patients undergoing hepatectomy.
      RESULTS: Administration of LSKL peptide attenuated Smad2 phosphorylation at 6 h.
      S-phase entry of hepatocytes was accelerated at 24 and 48 h by LSKL peptide,
      which resulted in faster recovery of the residual liver and bodyweight.
      Haematoxylin and eosin tissue staining and blood biochemical examinations
      revealed no significant adverse effects following the two LSKL peptide
      administrations. In the clinical setting, plasma TSP-1 levels were lowest on the
      first day after hepatectomy. However, plasma TSP-1 levels at this stage were
      significantly higher in patients with subsequent liver dysfunction compared with
      levels in those without liver dysfunction following hepatectomy. CONCLUSION: Only
      two doses of LSKL peptide during the early period after hepatectomy can promote
      liver regeneration. The transient inhibition of TSP-1/TGF-beta signal activation
      using LSKL peptide soon after hepatectomy may be a promising strategy to promote
      subsequent liver regeneration. Surgical relevance Although the mechanisms of
      liver regeneration after hepatectomy have been explored intensively in vivo, no
      therapeutic tools are thus far available to accelerate liver regeneration after
      hepatectomy in the clinical setting. Recently, the matricellular protein
      thrombospondin (TSP) 1, a major activator of latent transforming growth factor
      (TGF) beta1, has been identified as a negative regulator of liver regeneration
      after hepatectomy. In this study, the inhibition of TSP-1-mediated TGF-beta
      signal activation by LSKL (leucine-serine-lysine-leucine) peptide in the early
      period after hepatectomy accelerated liver regeneration without any adverse
      effects. In addition, continuous high plasma TSP-1 levels after hepatectomy were
      associated with liver damage in humans. The transient inhibition of TSP-1/TGF
      beta signal activation using LSKL peptide in the early period after hepatectomy
      could be a novel therapeutic strategy to accelerate liver regeneration after
      hepatectomy.

PMID- 25866940
TI  - Loss of Follow-up in Orthopaedic Trauma: Who Is Getting Lost to Follow-up?
AB  - OBJECTIVES: Noncompliance with postoperative follow-up visits remains a common
      problem in orthopaedic trauma. The aim of this study was to identify risk factors
      for loss of follow-up after orthopaedic trauma. DESIGN: Retrospective review.
      SETTING: Urban level 1 academic trauma center. PATIENTS: A total of 307 (226
      men/81 women) patients undergoing surgical treatment of their orthopaedic
      injuries were included in this study. The average age was 40.4 +/- 17 years.
      INTERVENTION: All patients were treated surgically for their orthopaedic injuries
      and were instructed to follow-up in the orthopaedic trauma clinic after hospital
      discharge. MAIN OUTCOME MEASUREMENTS: Noncompliance with follow-up appointment at
      6 months after injury. RESULTS: Over a 6-month postoperative period, a total of
      215 patients were noncompliant with at least one of their follow-up appointments
      between hospital discharge and the 6-month follow-up. A logistic regression
      showed male gender, uninsured or government insurance, and smoker to be
      statistically significant risk factors for noncompliance with the 6-month follow
      up (P < 0.05). Noncompliance with any follow-up appointment was significantly
      increased in patients with illicit drug abuse (P = 0.02) as per logistic
      regression analysis. CONCLUSIONS: Loss of follow-up is a common problem in
      orthopaedic trauma. Our study suggests different risk factors for noncompliance,
      including male gender, smoker, lack of commercial health insurance, and illicit
      drug abuse. Health care providers may consider establishing protocols for
      facilitating follow-up appointments to patients who are at risk for
      noncompliance.

PMID- 25866941
TI  - Misclassification of Pelvic Ring Injuries in the National Trauma Data Bank.
AB  - BACKGROUND: The American College of Surgeons has advocated for all trauma centers
      to participate in the National Trauma Data Bank (NTDB); however, no previous
      study has evaluated the accuracy of coding included in this data bank. The
      purpose of this study was to determine whether pelvic ring injuries are coded
      accurately in the NTDB and, if not, how they were misclassified. METHODS: A
      retrospective review of all pelvic ring injuries based on Abbreviated Injury
      Scale (AIS) codes was performed at a single level I academic trauma center from
      July 2010 to June 2013. Thin-section computed tomography (CT) scans in all
      patients were reviewed and classified using AIS codes: posterior arch intact,
      incomplete posterior arch, or complete posterior arch. The surgeon was blinded to
      the AIS code from the registry. These CT-based classifications were then compared
      with the pelvic ring injury codes designated in the trauma registry for each
      patient to evaluate agreement. RESULTS: Two hundred thirty-five patients with a
      mean age of 42 years had pelvic ring injuries in our registry. The agreement
      between trauma registry codes and CT reclassification was 24% in the intact
      group, 43% in the incomplete group, and 59% in the complete group. Using only the
      trauma registry codes, injuries were underclassified in 48% of the incomplete
      group and 76% of the intact group. CONCLUSIONS: Many pelvic ring injuries are
      miscoded and misclassified in the NTDB. The etiology of this misclassification is
      unclear, but any research data mined from these databases should be regarded
      cautiously.

PMID- 25866942
TI  - Catastrophic Thinking Is Associated With Finger Stiffness After Distal Radius
      Fracture Surgery.
AB  - OBJECTIVES: To identify demographic, injury-related, or psychologic factors
      associated with finger stiffness at suture removal and 6 weeks after distal
      radius fracture surgery. We hypothesize that there are no factors associated with
      distance to palmar crease at suture removal. DESIGN: Prospective cohort study.
      SETTING: Level I Academic Urban Trauma Center. PATIENTS: One hundred sixteen
      adult patients underwent open reduction and internal fixation of their distal
      radius fractures; 96 of whom were also available 6 weeks after surgery.
      INTERVENTION: None. MAIN OUTCOME MEASUREMENTS: At suture removal, we recorded
      patients' demographics, AO fracture type, carpal tunnel release at the time of
      surgery, pain catastrophizing scale, Whiteley Index, Patient Health Questionnaire
      9, and disabilities of the arm, shoulder, and hand questionnaire, 11-point
      ordinal measure of pain intensity, distance to palmar crease, and active flexion
      of the thumb through the small finger. At 6 weeks after surgery, we measured
      motion, disabilities of the arm, shoulder, and hand, and pain intensity.
      Prereduction and postsurgery radiographic fracture characteristics were assessed.
      RESULTS: Female sex, being married, specific surgeons, carpal tunnel release, AO
      type C fractures, and greater catastrophic thinking were associated with
      increased distance to palmar crease at suture removal. At 6 weeks, greater
      catastrophic thinking was the only factor associated with increased distance to
      palmar crease. CONCLUSIONS: Catastrophic thinking was a consistent and major
      determinant of finger stiffness at suture removal and 6 weeks after injury.
      Future research should assess if treatments that ameliorate catastrophic thinking
      can facilitate recovery of finger motion after operative treatment of a distal
      radius fracture. LEVEL OF EVIDENCE: Prognostic Level I. See Instructions for
      Authors for a complete description of levels of evidence.

PMID- 25866943
TI  - Osteoporosis treatment and fracture outcomes.

PMID- 25866945
TI  - Letter to the Editor: An Alternative Interpretation of Issues Surrounding the
      Exchange Rates Re: Dobie, R.A., & Clark, W.W. (2014) Exchange Rates for
      Intermittent and Fluctuating Occupational Noise: A Systematic Review of Studies
      of Human Permanent Threshold Shift, Ear Hear, 35, 86-96.

PMID- 25866944
TI  - Informational constraints on spontaneous visuomotor entrainment.
AB  - Past research has revealed that an individual's rhythmic limb movements become
      spontaneously entrained to an environmental rhythm if visual information about
      the rhythm is available and its frequency is near that of the individual's
      movements. Research has also demonstrated that if the eyes track an environmental
      stimulus, the spontaneous entrainment to the rhythm is strengthened. One
      hypothesis explaining this enhancement of spontaneous entrainment is that the
      limb movements and eye movements are linked through a neuromuscular coupling or
      synergy. Another is that eye-tracking facilitates the pick up of important
      coordinating information. Experiment 1 investigated the first hypothesis by
      evaluating whether any rhythmic movement of the eyes would facilitate spontaneous
      entrainment. Experiments 2 and 3 (respectively) explored whether eye-tracking
      strengthens spontaneous entrainment by allowing the pickup of trajectory
      direction change information or allowing an increase in the amount of information
      to be picked-up. Results suggest that the eye-tracking enhancement of spontaneous
      entrainment is a consequence of increasing the amount of information available to
      be picked-up. 

PMID- 25866946
TI  - Letter to the Editor: Scientific Rigor Required for a Re-Examination of Exchange
      Rate for Occupational Noise Measurements Re: Dobie, R.A., & Clark, W.W. (2014)
      Exchange Rates for Intermittent and Fluctuating Occupational Noise: A Systematic
      Review of Studies of Human Permanent Threshold Shift, Ear Hear, 35, 86-96.

PMID- 25866947
TI  - Response to Suter and NIOSH.

PMID- 25866954
TI  - Isolation and functional analysis of mitochondria from cultured cells and mouse
      tissue.
AB  - Comparison between two or more distinct groups, such as healthy vs. disease, is
      necessary to determine cellular status. Mitochondria are at the nexus of cell
      heath due to their role in both cell metabolism and energy production as well as
      control of apoptosis. Therefore, direct evaluation of isolated mitochondria and
      mitochondrial perturbation offers the ability to determine if organelle-specific
      (dys)function is occurring. The methods described in this protocol include
      isolation of intact, functional mitochondria from HEK cultured cells and mouse
      liver and spinal cord, but can be easily adapted for use with other cultured
      cells or animal tissues. Mitochondrial function assessed by TMRE and the use of
      common mitochondrial uncouplers and inhibitors in conjunction with a fluorescent
      plate reader allow this protocol not only to be versatile and accessible to most
      research laboratories, but also offers high throughput. 

PMID- 25866955
TI  - MoO3 Nanodots Decorated CdS Nanoribbons for High-Performance, Homojunction
      Photovoltaic Devices on Flexible Substrates.
AB  - The p-n homojunctions are essential components for high-efficiency optoelectronic
      devices. However, the lack of p-type doping in CdS nanostructures hampers the
      fabrication of efficient photovoltaic (PV) devices from homojunctions. Here we
      report a facile solution-processed method to achieve efficient p-type doping in
      CdS nanoribbons (NRs) via a surface charge transfer mechanism by using spin
      coated MoO3 nanodots (NDs). The NDs-decorated CdS NRs exhibited a hole
      concentration as high as 8.5 * 10(19) cm(-3), with the p-type conductivity
      tunable in a wide range of 7 orders of magnitude. The surface charge transfer
      mechanism was characterized in detail by X-ray photoelectron spectroscopy, Kelvin
      probe force microscopy, and first-principle calculations. CdS NR-homojunction PV
      devices fabricated on a flexible substrate exhibited a power conversion
      efficiency of 5.48%, which was significantly better than most of the CdS
      nanostructure-based heterojunction devices, presumably due to minimal junction
      defects. Devices made by connecting cells in series or in parallel exhibited
      enhanced power output, demonstrating the promising potential of the homojunction
      PV devices for device integration. Given the high efficiency of the surface
      charge transfer doping and the solution-processing capability of the method, our
      work opens up unique opportunities for high-performance, low-cost optoelectronic
      devices based on CdS homojunctions. 

PMID- 25866956
TI  - Dysplasia epiphysealis hemimelica (Trevor disease) of the ankle.
AB  - An 11-year-old boy presented with a 2-year history of left ankle pain and
      abnormal gait, worsened with sports activities such as football and wrestling. 

PMID- 25866957
TI  - Men in Papua New Guinea accurately report their circumcision status.
AB  - BACKGROUND: Male circumcision (MC) is a well-established component of HIV
      prevention in countries with high HIV prevalence and heterosexually driven
      epidemics. Delivery and monitoring of MC programs are reliant on good quality MC
      data. Such data are often generated through self-reported MC status surveys. This
      study examined self-reported MC status in comparison with genital photographs
      from men in Papua New Guinea (PNG). METHODS: This retrospective non
      interventional study collated self-reported MC status data from the
      'acceptability and feasibility of MC' study at 4 sites in PNG during 2010-2011.
      Participants reported their MC status based on an 8-category photographic
      classification covering the range of foreskin cutting practices in PNG. Genital
      photographs of 222 participants from this study were independently classified by
      2 investigators. The 8-category photographic classification was simplified into a
      3 category classification of 'no cut', 'straight cut' and 'round cut' before
      comparing for agreement between self-reporting and investigator assessment using
      Cohen's Kappa measure. RESULTS: Using the 3-category classification, there was
      90.6% (201/222) agreement between self-assessment and investigator classification
      (kappa value 0.805). Of the discordant 9.4% (21/222), 3.6% (8/222) self
      classified as having a cut foreskin (5 straight cut; 3 round cut) while
      investigators classified as having no cut; 4.1% (9/222) self-classified as having
      no cut while investigators classified them as having had a cut (6 straight cut; 3
      round cut) and 1.8% (4/222) self-classified as having a round cut while
      investigators classified as having a straight cut. Given the great variety of
      foreskin cutting practices and appearances, feasible explanations are suggested
      for two-thirds (13/21) of these discordant results. CONCLUSIONS: This study
      demonstrates a high level of agreement between self-reporting and investigator
      assessment of MC status in PNG and suggests self-reporting of MC status to be
      highly reliable among men in PNG.

PMID- 25866958
TI  - Preferences for trauma treatment: A systematic review of the empirical
      literature.
AB  - The prevalence of trauma histories and related psychological problems is high in
      general clinical settings, but little is known about trauma patient preferences
      for mental health treatment. The purpose of this article is to systematically
      review and synthesize the literature on treatment preferences in survivors of
      traumatic events. Studies were identified using comprehensive searches of
      PsycINFO, Medline, PubMed, Published International Literature on Traumatic
      Stress, and Cumulative Index to Nursing and Allied Health Literature databases.
      Included in the review were articles published between January 1980 and September
      2014, in English that reported patient preference of treatment for trauma related
      disorders in either clinical or nonclinical (e.g., analog) samples. The total
      number of individual participants was 6,091. Of the identified studies, 35 were
      quantitative and 6 were qualitative. Methodological concerns included the use of
      analog samples, small sample sizes, and the assessment of a limited number of
      treatment options (e.g., asking about only 1 type of psychotherapy or
      medication). Overall, participants expressed a preference for psychotherapy over
      medication and for talking about their trauma. Understanding and addressing
      trauma patient preferences may assist in improving treatment initiation as well
      as facilitate engagement, retention and outcome.

PMID- 25866959
TI  - Understanding how deployment experiences change over time: Comparison of female
      and male OEF/OIF and Gulf War veterans.
AB  - Despite increased attention to the evolving nature of war, the unique challenges
      of contemporary deployment, and women's changing role in warfare, few studies
      have examined differences in deployment stressors across eras of service or
      evaluated how gender differences in deployment experiences have changed over
      time. Using data collected from two national survey studies, we examined war
      cohort and gender differences in veterans' reports of both mission-related and
      interpersonal stressors during deployment. Although Operation Enduring Freedom
      and Operation Iraqi Freedom veterans reported more combat experiences and greater
      preparedness for deployment compared to Gulf War veterans, Gulf War veterans
      reported higher levels of other mission-related stressors, including difficult
      living and working environment, perceived threat, and potential exposure to
      nuclear, biological, and chemical weapons. Gender differences also emerged, with
      men reporting greater exposure to mission-related stressors and women reporting
      higher levels of interpersonal stressors. However, the size and nature of gender
      differences did not differ significantly when comparing veterans of the two eras.
      By understanding how risk factors for PTSD differ based on war era and gender,
      veterans' experiences can be better contextualized.

PMID- 25866960
TI  - Psychological first aid training for Lebanese field workers in the emergency
      context of the Syrian refugees in Lebanon.
AB  - The Syrian refugee crisis in Lebanon required a fast and efficient comprehensive
      rescue strategy. Professionals working in emergency response were neither
      prepared to provide psychological first aid nor prepared to screen for mental
      health disorders in child refugees. This article examines the efficacy of a
      national training program in psychological first aid (PFA) to enhance the
      readiness of mental health field workers in the Syrian refugee response.
      Participant (N = 109) were recruited from Lebanese ministries and nongovernmental
      organizations. They received a 2.5-day training on PFA and on screening for
      mental health disorders in children. Their knowledge and perceived readiness were
      assessed before the training, immediately after the training, and 1 month after
      the training using 2 evaluation forms. Evaluation Form A was a multiple choice
      questionnaire composed of 20 questions and created on the basis of the content of
      the training, and Evaluation Form B was a Likert-type scale of 20 items created
      based on the core components of PFA. The data of 60 participants were analyzed.
      The results showed a significant increase in knowledge and readiness,
      specifically on the components related to the principles and techniques of PFA.

PMID- 25866961
TI  - The effects of combat exposure, abusive violence, and sense of coherence on PTSD
      and depression in Portuguese colonial war veterans.
AB  - We analyzed the effects of 3 war components-combat exposure (CES), observation of
      abusive violence (OBS), and participation in abusive violence (PARTC)-and sense
      of coherence (SOC) on the development of both posttraumatic stress disorder
      (PTSD) and depression among a sample of war veterans. We also analyzed the role
      of SOC as a mediator of the effects of CES, OBS, and PARTC on both depression and
      PTSD symptoms. Sample was composed of 120 Portuguese Colonial War veterans. A
      binomial logistic regression analysis was performed to determine the effects of
      these variables on depression and PTSD diagnosis. Mediation test was performed by
      conducting several hierarchical regression analyses. Results showed that OBS and
      PARTC, and lower levels of SOC were associated with increased odds for exceeding
      the clinical cutoff scores for diagnosis of depression. All variables were
      associated with increased odds for exceeding the clinical cutoff scores for
      diagnosis of PTSD. In mediation analysis, at first step, PARTC was not a
      significant predictor of both PTSD and depression symptoms, and PARTC did not
      enter in subsequent analysis. SOC was a full mediator of the effects of OBS and
      CES on both depression and PTSD symptoms. We propose that treatment of war
      veterans should aim the reconciliation of traumatic incongruent experiences in
      veterans' personal schemas to strengthen veterans' sense of coherence, especially
      for those exposed to acts of abusive violence.

PMID- 25866962
TI  - Coping strategies and internal resources of dispositional optimism and mastery as
      predictors of traumatic exposure and of PTSD symptoms: A prospective study.
AB  - This prospective study aimed at examining the role of trait internal resources
      and coping strategies in predicting traumatic exposure and levels of
      posttraumatic stress disorder (PTSD) symptoms after such exposure. In total, 870
      Israeli students participated in the study, of whom 182 (20%) reported a lifetime
      history of traumatic exposure at baseline (t1), and a total of 231 (27%)
      respondents reported traumatic exposure during follow-up (t2, t3). After
      controlling the effect of lifetime history of traumatic exposure either by using
      it as a covariate in a multivariate analysis of covariance (MANCOVA) or as a
      predictor in regression analyses, the results indicate that individuals high on
      trait avoidance coping style and low on mastery are at a higher risk for
      traumatic exposure, while those high on trait problem-focused coping style,
      mastery and dispositional optimism are at a lower risk for PTSD symptoms after
      such exposure.

PMID- 25866963
TI  - Lifetime abuse and self-harm in people with severe mental illness: A structural
      equation model.
AB  - We tested the hypothesis that lifetime physical and sexual abuse would have
      direct effects on self-harm (i.e., thoughts of self-harm, self-harming behaviors,
      and suicide attempts) and indirect effects on self-harm via negative appraisals
      of trauma and psychiatric symptoms in a sample of 242 clients with severe mental
      illness (SMI). Structural equation modeling partly confirmed our expectations.
      Although there was no direct effect between abuse and self-harm, abuse and self
      harm appear to be fully mediated by negative appraisal and psychiatric symptoms.
      Limitations to this study include the cross-sectional nature of the research,
      which precludes firm causal inferences regarding the relationships among these
      factors. Longitudinal designs are needed to understand better the direct and
      indirect effects of abuse on people with SMI.

PMID- 25866964
TI  - Demonstration of the rat ischemic skin wound model.
AB  - The propensity for chronic wounds in humans increases with ageing, disease
      conditions such as diabetes and impaired cardiovascular function, and unrelieved
      pressure due to immobility. Animal models have been developed that attempt to
      mimic these conditions for the purpose of furthering our understanding of the
      complexity of chronic wounds. The model described herein is a rat ischemic skin
      flap model that permits a prolonged reduction of blood flow resulting in wounds
      that become ischemic and resemble a chronic wound phenotype (reduced
      vascularization, increased inflammation and delayed wound closure). It consists
      of a bipedicled dorsal flap with 2 ischemic wounds placed centrally and 2 non
      ischemic wounds lateral to the flap as controls. A novel addition to this
      ischemic skin flap model is the placement of a silicone sheet beneath the flap
      that functions as a barrier and a splint to prevent revascularization and reduce
      contraction as the wounds heal. Despite the debate of using rats for wound
      healing studies due to their quite distinct anatomic and physiologic differences
      compared to humans (i.e., the presence of a panniculus carnosus muscle, short
      life-span, increased number of hair follicles, and their ability to heal infected
      wounds) the modifications employed in this model make it a valuable alternative
      to previously developed ischemic skin flap models. 

PMID- 25866965
TI  - A technical perspective in modern tree-ring research--how to overcome
      dendroecological and wood anatomical challenges.
AB  - Dendroecological research uses information stored in tree rings to understand how
      single trees and even entire forest ecosystems responded to environmental changes
      and to finally reconstruct such changes. This is done by analyzing growth
      variations back in time and correlating various plant-specific parameters to (for
      example) temperature records. Integrating wood anatomical parameters in these
      analyses would strengthen reconstructions, even down to intra-annual resolution.
      We therefore present a protocol on how to sample, prepare, and analyze wooden
      specimen for common macroscopic analyses, but also for subsequent microscopic
      analyses. Furthermore we introduce a potential solution for analyzing digital
      images generated from common small and large specimens to support time-series
      analyses. The protocol presents the basic steps as they currently can be used.
      Beyond this, there is an ongoing need for the improvement of existing techniques,
      and development of new techniques, to record and quantify past and ongoing
      environmental processes. Traditional wood anatomical research needs to be
      expanded to include ecological information to this field of research. This would
      support dendro-scientists who intend to analyze new parameters and develop new
      methodologies to understand the short and long term effects of specific
      environmental factors on the anatomy of woody plants. 

PMID- 25866966
TI  - Ube3a reinstatement identifies distinct developmental windows in a murine
      Angelman syndrome model.
AB  - Angelman syndrome (AS) is a severe neurodevelopmental disorder that results from
      loss of function of the maternal ubiquitin protein ligase E3A (UBE3A) allele. Due
      to neuron-specific imprinting, the paternal UBE3A copy is silenced. Previous
      studies in murine models have demonstrated that strategies to activate the
      paternal Ube3a allele are feasible; however, a recent study showed that
      pharmacological Ube3a gene reactivation in adulthood failed to rescue the
      majority of neurocognitive phenotypes in a murine AS model. Here, we performed a
      systematic study to investigate the possibility that neurocognitive rescue can be
      achieved by reinstating Ube3a during earlier neurodevelopmental windows. We
      developed an AS model that allows for temporally controlled Cre-dependent
      induction of the maternal Ube3a allele and determined that there are distinct
      neurodevelopmental windows during which Ube3a restoration can rescue AS-relevant
      phenotypes. Motor deficits were rescued by Ube3a reinstatement in adolescent
      mice, whereas anxiety, repetitive behavior, and epilepsy were only rescued when
      Ube3a was reinstated during early development. In contrast, hippocampal synaptic
      plasticity could be restored at any age. Together, these findings suggest that
      Ube3a reinstatement early in development may be necessary to prevent or rescue
      most AS-associated phenotypes and should be considered in future clinical trial
      design. 

PMID- 25866967
TI  - Endothelium and NOTCH specify and amplify aorta-gonad-mesonephros-derived
      hematopoietic stem cells.
AB  - Hematopoietic stem cells (HSCs) first emerge during embryonic development within
      vessels such as the dorsal aorta of the aorta-gonad-mesonephros (AGM) region,
      suggesting that signals from the vascular microenvironment are critical for HSC
      development. Here, we demonstrated that AGM-derived endothelial cells (ECs)
      engineered to constitutively express AKT (AGM AKT-ECs) can provide an in vitro
      niche that recapitulates embryonic HSC specification and amplification.
      Specifically, nonengrafting embryonic precursors, including the VE-cadherin
      expressing population that lacks hematopoietic surface markers, cocultured with
      AGM AKT-ECs specified into long-term, adult-engrafting HSCs, establishing that a
      vascular niche is sufficient to induce the endothelial-to-HSC transition in
      vitro. Subsequent to hematopoietic induction, coculture with AGM AKT-ECs also
      substantially increased the numbers of HSCs derived from VE-cadherin+CD45+ AGM
      hematopoietic cells, consistent with a role in supporting further HSC maturation
      and self-renewal. We also identified conditions that included NOTCH activation
      with an immobilized NOTCH ligand that were sufficient to amplify AGM-derived HSCs
      following their specification in the absence of AGM AKT-ECs. Together, these
      studies begin to define the critical niche components and resident signals
      required for HSC induction and self-renewal ex vivo, and thus provide insight for
      development of defined in vitro systems targeted toward HSC generation for
      therapeutic applications.

PMID- 25866968
TI  - Lifespan of mice and primates correlates with immunoproteasome expression.
AB  - There is large variation in lifespan among different species, and there is
      evidence that modulation of proteasome function may contribute to longevity
      determination. Comparative biology provides a powerful tool for identifying genes
      and pathways that control the rate of aging. Here, we evaluated skin-derived
      fibroblasts and demonstrate that among primate species, longevity correlated with
      an elevation in proteasomal activity as well as immunoproteasome expression at
      both the mRNA and protein levels. Immunoproteasome enhancement occurred with a
      concurrent increase in other elements involved in MHC class I antigen
      presentation, including beta-2 microglobulin, (TAP1), and TAP2. Fibroblasts from
      long-lived primates also appeared more responsive to IFN-gamma than cells from
      short-lived primate species, and this increase in IFN-gamma responsiveness
      correlated with elevated expression of the IFN-gamma receptor protein IFNGR2.
      Elevation of immunoproteasome and proteasome activity was also observed in the
      livers of long-lived Snell dwarf mice and in mice exposed to drugs that have been
      shown to extend lifespan, including rapamycin, 17-alpha-estradiol, and
      nordihydroguaiaretic acid. This work suggests that augmented immunoproteasome
      function may contribute to lifespan differences in mice and among primate
      species. 

PMID- 25866969
TI  - Pharmacological HIF2alpha inhibition improves VHL disease-associated phenotypes
      in zebrafish model.
AB  - Patients with a germline mutation in von Hippel-Lindau (VHL) develop renal cell
      cancers and hypervascular tumors of the brain, adrenal glands, and pancreas as
      well as erythrocytosis. These phenotypes are driven by aberrant expression of
      HIF2alpha, which induces expression of genes involved in cell proliferation,
      angiogenesis, and red blood cell production. Currently, there are no effective
      treatments available for VHL disease. Here, using an animal model of VHL, we
      report a marked improvement of VHL-associated phenotypes following treatment with
      HIF2alpha inhibitors. Inactivation of vhl in zebrafish led to constitutive
      activation of HIF2alpha orthologs and modeled several aspects of the human
      disease, including erythrocytosis, pathologic angiogenesis in the brain and
      retina, and aberrant kidney and liver proliferation. Treatment of vhl(-/-) mutant
      embryos with HIF2alpha-specific inhibitors downregulated Hif target gene
      expression in a dose-dependent manner, improved abnormal hematopoiesis, and
      substantially suppressed erythrocytosis and angiogenic sprouting. Moreover,
      pharmacologic inhibition of HIF2alpha reversed the compromised cardiac
      contractility of vhl(-/-) embryos and partially rescued early lethality. This
      study demonstrates that small-molecule targeting of HIF2alpha improves VHL
      related phenotypes in a vertebrate animal model and supports further exploration
      of this strategy for treating VHL disease.

PMID- 25866970
TI  - TALE-mediated epigenetic suppression of CDKN2A increases replication in human
      fibroblasts.
AB  - Current strategies to alter disease-associated epigenetic modifications target
      ubiquitously expressed epigenetic regulators. This approach does not allow
      specific genes to be controlled in specific cell types; therefore, tools to
      selectively target epigenetic modifications in the desired cell type and
      strategies to more efficiently correct aberrant gene expression in disease are
      needed. Here, we have developed a method for directing DNA methylation to
      specific gene loci by conjugating catalytic domains of DNA methyltransferases
      (DNMTs) to engineered transcription activator-like effectors (TALEs). We
      demonstrated that these TALE-DNMTs direct DNA methylation specifically to the
      targeted gene locus in human cells. Further, we determined that minimizing direct
      nucleotide sequence repeats within the TALE moiety permits efficient lentivirus
      transduction, allowing easy targeting of primary cell types. Finally, we
      demonstrated that directed DNA methylation with a TALE-DNMT targeting the CDKN2A
      locus, which encodes the cyclin-dependent kinase inhibitor p16, decreased CDKN2A
      expression and increased replication of primary human fibroblasts, as intended.
      Moreover, overexpression of p16 in these cells reversed the proliferative
      phenotype, demonstrating the specificity of our epigenetic targeting. Together,
      our results demonstrate that TALE-DNMTs can selectively target specific genes and
      suggest that this strategy has potential application for the development of locus
      specific epigenetic therapeutics. 

PMID- 25866971
TI  - Airway epithelial SPDEF integrates goblet cell differentiation and pulmonary Th2
      inflammation.
AB  - Epithelial cells that line the conducting airways provide the initial barrier and
      innate immune responses to the abundant particles, microbes, and allergens that
      are inhaled throughout life. The transcription factors SPDEF and FOXA3 are both
      selectively expressed in epithelial cells lining the conducting airways, where
      they regulate goblet cell differentiation and mucus production. Moreover, these
      transcription factors are upregulated in chronic lung disorders, including
      asthma. Here, we show that expression of SPDEF or FOXA3 in airway epithelial
      cells in neonatal mice caused goblet cell differentiation, spontaneous
      eosinophilic inflammation, and airway hyperresponsiveness to methacholine. SPDEF
      expression promoted DC recruitment and activation in association with induction
      of Il33, Csf2, thymic stromal lymphopoietin (Tslp), and Ccl20 transcripts.
      Increased Il4, Il13, Ccl17, and Il25 expression was accompanied by recruitment of
      Th2 lymphocytes, group 2 innate lymphoid cells, and eosinophils to the lung.
      SPDEF was required for goblet cell differentiation and pulmonary Th2 inflammation
      in response to house dust mite (HDM) extract, as both were decreased in neonatal
      and adult Spdef(-/-) mice compared with control animals. Together, our results
      indicate that SPDEF causes goblet cell differentiation and Th2 inflammation
      during postnatal development and is required for goblet cell metaplasia and
      normal Th2 inflammatory responses to HDM aeroallergen.

PMID- 25866972
TI  - TIGIT and PD-1 impair tumor antigen-specific CD8+ T cells in melanoma patients.
AB  - T cell Ig and ITIM domain (TIGIT) is an inhibitory receptor expressed by
      activated T cells, Tregs, and NK cells. Here, we determined that TIGIT is
      upregulated on tumor antigen-specific (TA-specific) CD8+ T cells and CD8+ tumor
      infiltrating lymphocytes (TILs) from patients with melanoma, and these TIGIT
      expressing CD8+ T cells often coexpress the inhibitory receptor PD-1. Moreover,
      CD8+ TILs from patients exhibited downregulation of the costimulatory molecule
      CD226, which competes with TIGIT for the same ligand, supporting a TIGIT/CD226
      imbalance in metastatic melanoma. TIGIT marked early T cell activation and was
      further upregulated by T cells upon PD-1 blockade and in dysfunctional PD-1+TIM
      3+ TA-specific CD8+ T cells. PD-1+TIGIT+, PD-1-TIGIT+, and PD-1+TIGIT- CD8+ TILs
      had similar functional capacities ex vivo, suggesting that TIGIT alone, or
      together with PD-1, is not indicative of T cell dysfunction. However, in the
      presence of TIGIT ligand-expressing cells, TIGIT and PD-1 blockade additively
      increased proliferation, cytokine production, and degranulation of both TA
      specific CD8+ T cells and CD8+ TILs. Collectively, our results show that TIGIT
      and PD-1 regulate the expansion and function of TA-specific CD8+ T cells and CD8+
      TILs in melanoma patients and suggest that dual TIGIT and PD-1 blockade should be
      further explored to elicit potent antitumor CD8+ T cell responses in patients
      with advanced melanoma.

PMID- 25866974
TI  - Ring-Noose-String Technique Allows Adjustable Papillary Muscle Repositioning
      During Minimally Invasive Mitral Valve Repair in Patients with
      Functional/Ischemic Mitral Regurgitation.
AB  - In patients with functional/ischemic mitral regurgitation (FMR/IMR), mitral
      annuloplasty alone frequently results in recurrent regurgitation because of
      ongoing left ventricular dilatation and recurrent leaflet tethering. Adjunctive
      subvalvular approaches exist, but the technical shortcomings limit their clinical
      acceptance. A novel adjunctive technique was applied in three patients: A
      polytetrafluoroethylene string and noose were anchored to the posteromedial and
      anterolateral papillary muscle, respectively. The string ends were guided through
      the noose, exteriorized through the midposterior annulus into the left atrium,
      and length-adjusted during the saline test. The procedure allowed safe and
      straightforward papillary muscle repositioning and may stabilize repair results
      in FMR/IMR patients. 

PMID- 25866975
TI  - Clinical Relevance and Practical Value of Platelet Function Assessment Using
      Multiple Electrode Aggregometry during Extracorporeal Circulation.

PMID- 25866973
TI  - Ash1l controls quiescence and self-renewal potential in hematopoietic stem cells.
AB  - Rapidly cycling fetal and neonatal hematopoietic stem cells (HSCs) generate a
      pool of quiescent adult HSCs after establishing hematopoiesis in the bone marrow.
      We report an essential role for the trithorax group gene absent, small, or
      homeotic 1-like (Ash1l) at this developmental transition. Emergence and expansion
      of Ash1l-deficient fetal/neonatal HSCs were preserved; however, in young adult
      animals, HSCs were profoundly depleted. Ash1l-deficient adult HSCs had markedly
      decreased quiescence and reduced cyclin-dependent kinase inhibitor 1b/c
      (Cdkn1b/1c) expression and failed to establish long-term trilineage bone marrow
      hematopoiesis after transplantation to irradiated recipients. Wild-type HSCs
      could efficiently engraft when transferred to unirradiated, Ash1l-deficient
      recipients, indicating increased availability of functional HSC niches in these
      mice. Ash1l deficiency also decreased expression of multiple Hox genes in
      hematopoietic progenitors. Ash1l cooperated functionally with mixed-lineage
      leukemia 1 (Mll1), as combined loss of Ash1l and Mll1, but not isolated Ash1l or
      Mll1 deficiency, induced overt hematopoietic failure. Our results uncover a
      trithorax group gene network that controls quiescence, niche occupancy, and self
      renewal potential in adult HSCs. 

PMID- 25866976
TI  - Computed Tomography Scan Predicts Abdominal Interventions but Not Stroke after
      Surgery for Acute Type A Aortic Dissection.
AB  - BACKGROUND: We hypothesized that preoperative computed tomography (CT) is a
      predictor of abdominal intervention for visceral malperfusion and stroke after
      emergent surgery for acute type A aortic dissection (AAAD). METHODS: A total of
      90 patients, mean (+/- SD [standard deviation]) age 62 (+/- 12) years, 76% males,
      undergoing emergent surgery for AAAD at our institution from May 2008 to August
      2013 were included. All clinical data were collected prospectively and correlated
      to CT images. RESULTS: At initial presentation 9 (10%) patients showed
      preoperative focal neurologic deficit or coma, 10 patients (11%) complained of
      abdominal pain, and the logistic EuroSCORE was 44 (+/- 22). Hemiarch replacement
      was performed in 96%, total arch in 4%. The duration of hypothermic circulatory
      arrest (HCA) at 28 degrees C bladder temperature was 26 (+/- 19) minutes. Cross
      clamp time was 88 (+/- 39) minutes, and cardiopulmonary bypass (CPB) time 148 (+/
      49) minutes. Overall 30-day mortality was 13%. Moreover, 12 (13%) patients
      required postoperative abdominal interventions for suspected visceral
      malperfusion; stroke occurred in 25 (28%) patients. Logistic regression revealed
      that "dissection of the celiac trunk and/or the superior mesenteric artery" in
      preoperative CT images is a predictor of postoperative abdominal interventions
      for visceral malperfusion (p = 0.03), but preoperative abdominal pain is not
      similarly predictive. Postoperative stroke is best predicted by preoperative
      neurologic symptoms (p = 0.01), but not by supra-aortic vessel dissection in
      preoperative CT images. CONCLUSION: In patients undergoing surgery for AAAD,
      analysis of preoperative CT images allows identifying those with a high risk of
      postoperative abdominal intervention for visceral malperfusion. Postoperative
      stroke is best predicted by preoperative neurologic symptoms.

PMID- 25866977
TI  - One-Year Patency of Valvulotomized Vein Grafts Is Similar to That of Arterial
      Grafts.
AB  - BACKGROUND:  Inferior vein graft patency after coronary artery bypass grafting
      (CABG) is attributed to various factors. Venous valves may limit flow, cause
      thrombus formation, and diminish diastolic backflow. The aim of our study was to
      compare clinical outcome and midterm patency rate of valvulotomized vein grafts
      and arterial grafts in patients undergoing CABG. METHODS:  Between 2007 and 2010,
      valvulotomized saphenous vein segments were used to graft the right coronary
      artery (RCA) in 147 patients undergoing CABG with mean 2.8 +/- 1 arterial and 1.5
      +/- 0.6 venous anastomoses. Outcome, reintervention, and reoperation were
      assessed after 4 +/- 1.6 years. Intraoperative bypass flow rate was measured
      before and after valvulotomy of venous bypass grafts in 12 patients. Patency of
      the grafts was assessed by means of multislice computed tomography (MSCT) in 45
      patients. RESULTS:  A total of 102 patients underwent isolated CABG and 45 had
      combined procedures. In-hospital mortality was 2%. At 4 years' clinical follow
      up, 95% of the patients were asymptomatic. Five patients underwent recoronary
      angiography because of angina pectoris. The MSCT and reangiography patency rate
      of all valvulotomized saphenous vein grafts was 97.1 versus 95.8% of arterial
      grafts 18 +/- 6 months postoperatively. Intraoperative measurements showed a
      significant increase (+20.2 mL/min; p = 0.01) of flow in the venous bypass grafts
      to the RCA after valvulotomy. There were no reoperations at the latest follow-up.
      CONCLUSION:  Patients with valvulotomized venous grafts had good clinical
      outcome. The one-year patency rate of those grafts is comparable to that of
      arterial grafts. However, long-term results and angiography studies will be
      needed to strengthen these findings.

PMID- 25866978
TI  - Robot-Assisted Thoracoscopic Surgery versus Video-Assisted Thoracoscopic Surgery
      for Lung Lobectomy: Can a Robotic Approach Improve Short-Term Outcomes and
      Operative Safety?
AB  - Background Minimally invasive surgery has been recently recommended for treatment
      of early-stage non-small cell lung cancer. Despite the recent increase of robotic
      surgery, the place and potential advantages of the robot in thoracic surgery has
      not been well defined until now. Methods We reviewed our prospective database for
      retrospective comparison of our first 28 video-assisted thoracoscopic surgery
      lobectomies (V group) and our first 28 robotic lobectomies (R group). Results No
      significant difference was shown in median operative time between the two groups
      (185 vs. 190 minutes, p = 0.56). Median preincision time was significantly longer
      in the R group (80 vs. 60 minutes, P < 0.0001). The rate of emergency conversion
      for uncontrolled bleeding was lower in the R group (one vs. four). Median length
      of stay was comparable (6 days in the R group vs. 7 days in the V group, p = 0.4)
      with no significant difference in the rate of postoperative complications (eight
      Grade I in both groups, four Grade III or IV in the V group vs. six in the R
      group, according to the Clavien-Dindo classification, p = 0.93). No postoperative
      cardiac morbidity was observed in the R group. Median drainage time was similar
      (5 days, p = 0.78), with a rate of prolonged air leak slightly higher in the R
      group (25 vs. 17.8%, p = 0.74). Conclusion Perioperative outcomes are similar
      even in the learning period but robotic approach seems to offer more operative
      safety with fewer conversions for uncontrolled bleeding. 

PMID- 25866979
TI  - Economic and clinical benefit of collagenase ointment compared to a hydrogel
      dressing for pressure ulcer debridement in a long-term care setting.
AB  - INTRODUCTION: The purpose of this study is to determine the cost-effectiveness of
      collagenase ointment relative to autolysis with a hydrogel dressing when
      debriding necrotic pressure ulcers in a long-term care setting. METHODS: A Markov
      decision process model with 2 states (necrotic nonviable wound bed transitioning
      to a granulated viable wound bed) was developed using data derived from a
      prospective, randomized, 6-week, single-center trial of 27 institutionalized
      subjects with pressure ulcers that were >= 85% necrotic nonviable tissue. Direct
      medical costs from the payer perspective included study treatments, wound
      treatment supplies, and nursing time. Clinical benefit was measured as
      "granulation days" and was derived from the time-dependent debridement rates of
      the alternative products. RESULTS: The average cost per patient for 42 days of
      pressure ulcer care was $1,817 in 2012 for the collagenase group and $1,611 for
      the hydrogel group. Days spent with a granulated wound were 3.6 times higher for
      collagenase (23.4 vs 6.5) than with the hydrogel. The estimated cost per
      granulation day was > 3.2 times higher for hydrogel ($249) vs collagenase ($78).
      CONCLUSIONS: In this economic analysis based on a randomized, controlled clinical
      trial, collagenase ointment resulted in a faster time to complete debridement and
      was more cost-effective than hydrogel autolysis for pressure ulcers in a long
      term care setting. Even though collagenase ointment has a higher acquisition cost
      than hydrogel, the clinical benefit offsets the initial cost difference,
      resulting in lower cost per granulation day to the nursing home over the course
      of the 42-day analysis.

PMID- 25866980
TI  - Neutrophilic dermatosis of the dorsal hand.
AB  - Neutrophilic dermatosis of the dorsal hands (NDDH) is a rare condition often
      misdiagnosed as a localized cutaneous infection. A type of neutrophilic
      dermatosis, NDDH is considered to be a subset of Sweet's syndrome and is similar
      to pyoderma gangrenosum. The authors report 2 cases of male patients who
      presented with persistent ulcerative skin lesions. In both cases, biopsy revealed
      neutrophilic infiltration consistent with NDDH. Patient 1 had been unsuccessfully
      treated with antibiotics. Lesion biopsy showed epidermal hyperplasia with
      spongiosis and overlying scale crust, as well as dense neutrophilic infiltration
      of the underlying dermis. Periodic acid-Schiff (PAS) stain was negative for
      fungal and yeast organisms. A biopsy of a lesion from patient 2 indicated focal
      parakeratosis, perivascular inflammatory cell infiltrate, and scarring. Both
      patients were prescribed oral and/or topical corticosteroids and the condition
      resolved in 1-2 months. The clinical presentation, histological features, and
      excellent response to corticosteroid treatment are consistent with diagnosis of
      NDDH. Delayed recognition of neutrophilic dermatosis and treatment of secondary
      infection resulted in delayed treatment. Improved recognition of neutrophilic
      dermatoses is important for optimal management of NDDH.    . 

PMID- 25866981
TI  - Evaluation of an antimicrobial silver foam dressing.
AB  - CuraVAC Ag, a product that delivers negative pressure wound therapy through a
      polyurethane foam dressing, contains silver nanoparticles, which, when moistened
      with water, release silver ions onto a wound surface. The in vitro antimicrobial
      action of silver can destroy both gram-positive and gram-negative bacteria, as
      well as methicillin-resistant Staphylococcus aureus (MRSA). The purpose of this
      study was to assess the efficacy and in vivo outcomes of using the product.
      METHODS: Thirty-six female Sprague-Dawley white rats, 8-weeks old and 250 g - 300
      g in weight, were used. The experimental product was prepared using a vacuum
      assisted closure (VAC) kit and coating it using the silver nanoparticles. For the
      control group, a 10% povidone-iodine solution was applied. RESULTS: All groups
      showed decreases in wound area over time, in the order CuraVAC Ag (group A) >
      CuraVAC (group B) > control (group C). On the third, fifth, and seventh days,
      wound healing efficacy scores increased in both group A and group C. Groups A and
      B showed more rapid decreases than group C in bacterial culture from wounds.
      CONCLUSION: CuraVAC Ag may be useful for treatment of wounds infected with
      bacteria.   .

PMID- 25866982
TI  - Clinical experience with the surgicel family of absorbable hemostats (oxidized
      regenerated cellulose) in neurosurgical applications: a review.
AB  - INTRODUCTION: Oxidized regenerated cellulose has a long history of safe and
      effective use in the surgical setting. Surgicel Original, Fibrillar and Nu-Knit
      absorbable hemostats are composed of oxidized regenerated cellulose and are
      sterile, absorbable knitted fabrics that are flexible and adhere readily to
      bleeding surfaces. The purpose of this paper is to discuss neurosurgical
      applications for these absorbable hemostatic agents. METHODS: The authors
      reviewed the literature and described their clinical experience with Surgicel
      hemostatic products. RESULTS: Neurosurgical applications of the hemostatic
      products include the management of diffuse capillary oozing following bipolar
      cautery in brain tumor resection beds and the control of epidural oozing during
      spinal surgery. As an adjunct to standard hemostatic procedures, these products
      facilitate rapid hemostasis and have bactericidal activity that extend to
      antibiotic-resistant organisms such as methicillin-resistant Staphylococcus
      aureus, Staphylococcus epidermidis, and Streptococcus pneumonia, as well as
      Pseudomonas aeruginosa. Although generally safe and well-tolerated, these
      hemostatic agents should be removed when used around, in, or in proximity to,
      foramina in bone, areas of bony confine, the spinal cord, and/or the optic nerve
      or chiasm because it may otherwise swell and cause unwanted pressure. CONCLUSION:
      The physical, hemostatic, and bactericidal characteristics of this material makes
      it a useful adjunct for conventional hemostatic and controlling capillary,
      venous, and small arterial hemorrhage during neurosurgery.  .

PMID- 25866983
TI  - Sustained antiemetic responses with APF530 (sustained-release granisetron) during
      multiple cycles of emetogenic chemotherapy.
AB  - BACKGROUND: A phase 3 trial in patients with cancer who received chemotherapy has
      shown that subcutaneous (SC) APF530, a sustained-delivery formulation of
      granisetron, is noninferior to palonosetron in preventing acute (0-24 hours) and
      delayed (>24-120 hours) chemotherapy-induced nausea and vomiting (CINV).
      OBJECTIVES: To investigate the sustainability of APF530 antiemetic responses
      during multiple chemotherapy cycles. METHODS: 1,395 patients receiving moderately
      or highly emetogenic chemotherapy (MEC and HEC, respectively) were randomized
      either to APF530 250 or 500 mg SC (containing granisetron 5 or 10 mg,
      respectively) or palonosetron 0.25 mg intravenously before cycle 1 of
      chemotherapy. Patients who received palonosetron in cycle 1 were rerandomized in
      cycles 2-4 to APF530 250 or 500 mg; those who received APF530 in cycle 1
      continued their APF530 dose. Between-group response rates were compared using the
      Fisher exact test. RESULTS: Complete response (CR; no emesis, no rescue
      medication) for APF530 500 mg with HEC increased from 81.3% to 87.8% over 4
      cycles in the acute phase of CINV, and from 67.1% to 83.1% in the delayed phase.
      Rates were slightly lower with MEC. Within-cycle CR rates between APF530 doses
      showed no significant differences. With HEC, APF530 500 mg provided sustained CRs
      through 4 cycles of chemotherapy in 68.4% of patients in the acute phase and in
      57.9% in the delayed phase; with MEC, corresponding CRs were 56.5% and 41.3%.
      Nausea prevention was nearly as effective as emesis prevention. LIMITATIONS:
      Chemotherapy emetogenicity was classified according to Hesketh criteria during
      the time of this study. However, subsequent post hoc analyses indicate that
      reclassification according to newer ASCO emetogenicity guidelines did not alter
      the original study noninferiority conclusions. CONCLUSIONS: CR rates with APF530
      during the acute and delayed phases of CINV in MEC and HEC were maintained over
      multiple cycles.

PMID- 25866984
TI  - Women with self-reported lower-limb lymphedema after treatment for gynecological
      cancers: are they more likely to self-report psychosocial symptoms and less
      likely to use services?
AB  - BACKGROUND: Survivorship for gynecological cancers has increased because of
      improved screening and treatment. Use of supportive care services after treatment
      is important to improve patient quality of life. OBJECTIVES: To assess self
      reported lower-limb lymphedema (LLL), depression, anxiety, quality of life, unmet
      supportive care needs, and service use among gynecological cancer survivors.
      METHODS: In 2010, a population-based, cross-sectional mail survey was conducted
      among 160 gynecological cancer survivors 5-30 months after their diagnoses
      (response rate, 53%). RESULTS: Overall, 30% of women self-reported symptoms of
      LLL, 21% and 24% self-reported symptoms of depression or anxiety, respectively.
      Women with LLL were more likely to also report symptoms of depression or anxiety,
      and had higher unmet supportive care needs. Services needed but not used by 10%
      15% of women with LLL, anxiety, or depression were those of a lymphedema
      specialist, pain specialist, and physiotherapist for LLL, and a psychiatrist,
      psychologist, and pain specialist for anxiety and depression. LIMITATIONS: Small
      sample size, self-reported data, limited generalization to other countries,
      underrepresentation of older women (age >70 years) and women from non-Caucasian
      backgrounds. CONCLUSIONS: Women with LLL or high distress were less likely to use
      services they needed.

PMID- 25866985
TI  - Perceptions about participation in cancer clinical trials in New York state.
AB  - BACKGROUND: Clinical trials are valuable in advancing cancer care through the
      investigation of ways in which to better prevent, detect and diagnose, and/or
      treat cancer. Recruitment of adults into clinical trials has historically been
      low. OBJECTIVE: To survey adult cancer patients who reside in New York state to
      better understand their participation in and attitudes about clinical trials.
      METHODS: From January 2012-April 2013, we conducted a one-time survey about
      clinical trials in 8 cancer-treatment or cancer-patient support organizations in
      the state. Surveys were offered in person and online to adults with a past or
      current cancer diagnosis. Analysis was limited to adults who resided in the state
      and provided a self-reported status of previous participation in clinical trials.
      RESULTS: Of the 1,832 participants who completed the survey, 1,475 were included
      in the analysis. Our sample represented all regions of the state. Most of the
      respondents (68.1%) had never participated in a clinical trial. Almost 32% said
      they had never received information about research studies. Most (84%) felt that
      patients should be asked to participate in clinical trials, but fewer (70%) were
      willing to be approached about participation. LIMITATIONS: The sample is
      predominantly white and female and overrepresents breast and hematologic cancers.
      CONCLUSIONS: Increased outreach coupled with a team approach to educate and
      enroll patients in clinical trials may be the necessary first steps to increase
      participation in trials and ensure a diverse sample of participants.

PMID- 25866986
TI  - Synthetic methodology for asymmetric ferrocene derived bio-conjugate systems via
      solid phase resin-based methodology.
AB  - Early detection is a key to successful treatment of most diseases, and is
      particularly imperative for the diagnosis and treatment of many types of cancer.
      The most common techniques utilized are imaging modalities such as Magnetic
      Resonance Imaging (MRI), Positron Emission Topography (PET), and Computed
      Topography (CT) and are optimal for understanding the physical structure of the
      disease but can only be performed once every four to six weeks due to the use of
      imaging agents and overall cost. With this in mind, the development of "point of
      care" techniques, such as biosensors, which evaluate the stage of disease and/or
      efficacy of treatment in the clinician's office and do so in a timely manner,
      would revolutionize treatment protocols.1 As a means to exploring ferrocene based
      biosensors for the detection of biologically relevant molecules2, methods were
      developed to produce ferrocene-biotin bio-conjugates described herein. This
      report will focus on a biotin-ferrocene-cysteine system that can be immobilized
      on a gold surface.

PMID- 25866987
TI  - BILATERAL RAPIDLY DESTRUCTIVE HIP OSTEOARTHRITIS: A CASE REPORT.
AB  - Although hip osteoarthritis usually shows a slow progression, a rapidly
      destructive osteoarthritis is observed in approximately 10% of patients. We aimed
      to present a case with rapidly destructive osteoarthritis in bilateral hip
      joints. A 78-year-old male patient was admitted due to pain in hip joints. In
      examination, hip movements were minimally painful and limited. The patient was
      able to walk independently with a cane. When he re-applied six months later, hip
      movements were severely limited and painful. In plain radiographs, while a slight
      narrowing in hip joint space, sclerosis and minimal osteophyte had been observed
      at the first administration, extreme narrowing, subluxation, flattening of
      femoral head, increased sclerosis, resorption in femoral head and acetabulum were
      detected six months later. We consider that hip osteoarthritis in elderly people
      should be monitored at frequent intervals in terms of clinic and radiological
      progression. 

PMID- 25866989
TI  - Chemoresponsive Colloidosomes via Ag+ Soldering of Surface-Assembled Nanoparticle
      Monolayers.
AB  - Colloidosomes with a hollow interior and a porous plasmonic shell are highly
      desired for many applications including nanoreactors, surface-enhanced Raman
      scattering (SERS), photothermal therapy, and controlled drug release. We herein
      report a silica nanosphere-templated electrostatic self-assembly in conjunction
      with a newly developed Ag(+) soldering to fabricate gold colloidosomes toward
      multifunctionality and stimuli-responsibility. The gold colloidosomes are capable
      of capturing a nanosized object and releasing it via structural dissociation upon
      responding to a biochemical input (GSH, glutathione) at a concentration close to
      its cellular level. In addition, the colloidosomes have a tunable nanoporous
      shell composed of strongly coupled gold nanoparticles, which exhibit broadened
      near-infrared plasmon resonance. These features along with the simplicity and
      high tunability of the fabrication process make the gold colloidosomes quite
      promising for applications in a chemical or cellular environment. 

PMID- 25866988
TI  - Long term intravital multiphoton microscopy imaging of immune cells in healthy
      and diseased liver using CXCR6.Gfp reporter mice.
AB  - Liver inflammation as a response to injury is a highly dynamic process involving
      the infiltration of distinct subtypes of leukocytes including monocytes,
      neutrophils, T cell subsets, B cells, natural killer (NK) and NKT cells.
      Intravital microscopy of the liver for monitoring immune cell migration is
      particularly challenging due to the high requirements regarding sample
      preparation and fixation, optical resolution and long-term animal survival. Yet,
      the dynamics of inflammatory processes as well as cellular interaction studies
      could provide critical information to better understand the initiation,
      progression and regression of inflammatory liver disease. Therefore, a highly
      sensitive and reliable method was established to study migration and cell-cell
      interactions of different immune cells in mouse liver over long periods (about 6
      hr) by intravital two-photon laser scanning microscopy (TPLSM) in combination
      with intensive care monitoring. The method provided includes a gentle preparation
      and stable fixation of the liver with minimal perturbation of the organ; long
      term intravital imaging using multicolor multiphoton microscopy with virtually no
      photobleaching or phototoxic effects over a time period of up to 6 hr, allowing
      tracking of specific leukocyte subsets; and stable imaging conditions due to
      extensive monitoring of mouse vital parameters and stabilization of circulation,
      temperature and gas exchange. To investigate lymphocyte migration upon liver
      inflammation CXCR6.gfp knock-in mice were subjected to intravital liver imaging
      under baseline conditions and after acute and chronic liver damage induced by
      intraperitoneal injection(s) of carbon tetrachloride (CCl4). CXCR6 is a chemokine
      receptor expressed on lymphocytes, mainly on Natural Killer T (NKT)-, Natural
      Killer (NK)- and subsets of T lymphocytes such as CD4 T cells but also mucosal
      associated invariant (MAIT) T cells1. Following the migratory pattern and
      positioning of CXCR6.gfp+ immune cells allowed a detailed insight into their
      altered behavior upon liver injury and therefore their potential involvement in
      disease progression.

PMID- 25866990
TI  - Examining Reaction Specificity in PvcB, a Source of Diversity in Isonitrile
      Containing Natural Products.
AB  - Many bacteria produce isonitrile-containing natural products that are derived
      from aromatic amino acids. The synthetic clusters that control biosynthesis most
      commonly encode two enzymes, designated PvcA and PvcB, as well as additional
      enzymes that direct synthesis of the natural product. The PvcA enzyme installs
      the isonitrile moiety at the amino group of either tyrosine or tryptophan, as
      dictated by the particular pathway. The common pathway intermediate produced by
      PvcA is directed toward different ultimate products by PvcB, a member of the
      family of Fe(2+), alpha-ketoglutarate-dependent oxygenases. To continue our
      investigation of the structural and functional properties of the isonitrile
      biosynthetic pathways, we present here a study of the PvcB homologues from three
      organisms. Two pathways, derived from Pseudomonas aeruginosa and Xenorhabdus
      nematophila, produce known products. A third PvcB homologue from Erwinia
      amylovora is part of an uncharacterized pathway. Our results demonstrate the
      diversity of reactions catalyzed. Although all PvcB enzymes catalyze the
      hydroxylation of the tyrosine isonitrile substrate, the elimination of the
      hydroxyl in Pseudomonas and Erwinia is driven by deprotonation at Calpha,
      resulting in the initial production of an unsaturated tyrosine isonitrile product
      that then cyclizes to a coumarin derivative. PvcB from Xenorhabdus, in contrast,
      catalyzes the same oxygenation, but loss of the hydroxyl group is accompanied by
      decarboxylation of the intermediate. Steady-state kinetic analysis of the three
      reactions and a docking model for the binding of the tyrosine isonitrile
      substrate in the PvcB active site highlight subtle differences between the PvcB
      homologues. 

PMID- 25866991
TI  - Dual emissive manganese and copper Co-doped Zn-In-S quantum dots as a single
      color-converter for high color rendering white-light-emitting diodes.
AB  - Novel white light emitting diodes (LEDs) with environmentally friendly dual
      emissive quantum dots (QDs) as single color-converters are one of the most
      promising high-quality solid-state lighting sources for meeting the growing
      global demand for resource sustainability. A facile method was developed for the
      synthesis of the bright green-red-emitting Mn and Cu codoped Zn-In-S QDs with an
      absorption bangdgap of 2.56 eV (485 nm), a large Stokes shift of 150 nm, and high
      emission quantum yield up to 75%, which were suitable for warm white LEDs based
      on blue GaN chips. The wide photoluminescence (PL) spectra composed of Cu-related
      green and Mn-related red emissions in the codoped QDs could be controlled by
      varying the doping concentrations of Mn and Cu ions. The energy transfer
      processes in Mn and Cu codoped QDs were proposed on the basis of the changes in
      PL intensity and lifetime measured by means of steady-state and time-resolved PL
      spectra. By integrating these bicolor QDs with commercial GaN-based blue LEDs,
      the as-fabricated tricolor white LEDs showed bright natural white light with a
      color rendering index of 95, luminous efficacy of 73.2 lm/W, and color
      temperature of 5092 K. These results indicated that (Mn,Cu):Zn-In-S/ZnS QDs could
      be used as a single color-converting material for the next generation of solid
      state lighting. 

PMID- 25866992
TI  - Photoionization of Benzophenone in the Gas Phase: Theory and Experiment.
AB  - We report on the single photoionization of jet-cooled benzophenone using a
      tunable source of VUV synchrotron radiation coupled with a photoion/photoelectron
      coincidence acquisition device. The assignment and the interpretation of the
      spectra are based on a characterization by ab initio and density functional
      theory calculations of the geometry and of the electronic states of the cation.
      The absence of structures in the slow photoelectron spectrum is explained by a
      congestion of the spectrum due to the dense vibrational progressions of the very
      low frequency torsional mode in the cation either in pure form or in combination
      bands. Also a high density of electronic states has been found in the cation.
      Presently, we estimate the experimental adiabatic and vertical ionization energy
      of benzophenone at 8.80 +/- 0.01 and 8.878 +/- 0.005 eV, respectively. The
      ionization energy as well as the energies of the excited states are compared to
      the calculated ones. 

PMID- 25866994
TI  - Solid-Phase Total Synthesis of Bogorol A: Stereocontrolled Construction of
      Thermodynamically Unfavored (E)-2-Amino-2-butenamide.
AB  - Bogorol A [(E)-1], a potent antibiotic against methicillin-resistant
      Staphylococcus aureus and vancomycin-resistant Enterococcus spp., possesses a
      thermodynamically unfavored (E)-2-amino-2-butenamide within its linear
      dodecapeptide sequence. The highly efficient total synthesis of natural (E)
      isomer (E)-1 and its artificial (Z)-isomer (Z)-1 by employing a full solid-phase
      strategy is reported. The (E)- and (Z)-2-amino-2-butenamide moieties were
      stereoselectively constructed by applying traceless Staudinger ligation on the
      resin. Interestingly, (E)- and (Z)-1 showed comparable antimicrobial activity
      (MIC = 4 MUg/mL). 

PMID- 25866993
TI  - The Protective Effect of Interleukin-37 on Vascular Calcification and
      Atherosclerosis in Apolipoprotein E-Deficient Mice with Diabetes.
AB  - Interleukin (IL)-37 is a newly discovered member of the cytokine IL-1 family.
      Recent evidence suggests that IL-37, an anti-inflammatory factor, may have a role
      in atherosclerosis. In this study we used apoE-deficient diabetic mice, an
      established animal model, to examine the effects of IL-37 on the progression of
      vascular calcification and atherosclerosis. Compared with the control groups, IL
      37-treated (with injection of recombinant protein for 16 weeks) animals had
      significantly less calcification areas detected by both von Kossa and Alizarin
      Red staining, and much smaller plaque size of the atherosclerotic lesions and
      lower plaque vulnerability scores detected by hematoxylin-eosin staining in the
      aorta root. Our data also showed that IL-37 treatment caused elevated
      concentrations of osteoprotegerin (OPG) in serum. We detected that the group that
      received additional anti-OPG antibody reduced the effect of IL-37 treatment. The
      group that received both IL-37 and anti-OPG had significant larger percentage
      area of calcified lesion and atherosclerotic plaque size than the IL-37-treated
      group. Significant changes in disease-relevant cytokines (eg, ALP, BMP-2, TNF
      alpha, IL-18, and IL-10) were also elicited. This is the first report that IL-37
      could attenuate not only atherosclerosis, but also vascular calcification. This
      study may offer a therapeutic potential for the prevention and treatment of
      calcification and atherosclerotic disease. 

PMID- 25866996
TI  - Polyoxometalate-based nickel clusters as visible light-driven water oxidation
      catalysts.
AB  - Three new polyoxometalate(POM)-based polynuclear nickel clusters,
      Na24[Ni12(OH)9(CO3)3(PO4)(SiW9O34)3].56H2O (1),
      Na25[Ni13(H2O)3(OH)9(PO4)4(SiW9O34)3].50H2O (2), and
      Na50[Ni25(H2O)2OH)18(CO3)2(PO4)6(SiW9O34)6].85H2O (3) were synthesized and
      structurally characterized. Compounds 1-3 contain {Ni12}, {Ni13} and {Ni25} core,
      respectively, connected by the inorganic {OH}, {PO4} and/or {CO3} linkers and
      encapsulated by the lacunary A-alpha-{SiW9O34} POM units. Compound 3 represents
      the currently largest POM-based Ni clusters. All three compounds contain {Ni3O3}
      quasi-cubane or {Ni4O4} cubane units, which are similar to the natural oxygen
      evolving center {Mn4O5Ca} in photosystem II (PSII). Visible light-driven water
      oxidation experiments with compounds 1-3 as the homogeneous catalysts indicate
      that all three compounds show good photocatalytic activities. The O2 evolution
      amount corresponds to a high TON of 128.2 for 1, 147.6 for 2, and 204.5 for 3,
      respectively. Multiple experiments including dynamic light-scattering, UV-vis
      absorption, catalysts aged experiments, tetra-n-heptylammonium nitrate (THpANO3)
      toluene extraction, and capillary electrophoretic measurements results confirm
      that compounds 1-3 are dominant active catalysts but not Ni(2+) ions(aq) or
      nickel oxide under the photocatalytic conditions. The above research results
      indicate a new and all-inorganic polynuclear Ni-based structural model as the
      visible light-driven water oxidation catalysts. 

PMID- 25866995
TI  - Multistep current signal in protein translocation through graphene nanopores.
AB  - In nanopore sensing experiments, the properties of molecules are probed by the
      variation of ionic currents flowing through the nanopore. In this context, the
      electronic properties and the single-layer thickness of graphene constitute a
      major advantage for molecule characterization. Here we analyze the translocation
      pathway of the thioredoxin protein across a graphene nanopore, and the related
      ionic currents, by integrating two nonequilibrium molecular dynamics methods with
      a bioinformatic structural analysis. To obtain a qualitative picture of the
      translocation process and to identify salient features we performed unsupervised
      structural clustering on translocation conformations. This allowed us to identify
      some specific and robust translocation intermediates, characterized by
      significantly different ionic current flows. We found that the ion current
      strictly anticorrelates with the amount of pore occupancy by thioredoxin
      residues, providing a putative explanation of the multilevel current scenario
      observed in recently published translocation experiments. 

PMID- 25866997
TI  - Analysis of cardiomyocyte development using immunofluorescence in embryonic mouse
      heart.
AB  - During heart development, the generation of myocardial-specific structural and
      functional units including sarcomeres, contractile myofibrils, intercalated
      discs, and costameres requires the coordinated assembly of multiple components in
      time and space. Disruption in assembly of these components leads to developmental
      heart defects. Immunofluorescent staining techniques are used commonly in
      cultured cardiomyocytes to probe myofibril maturation, but this ex vivo approach
      is limited by the extent to which myocytes will fully differentiate in culture,
      lack of normal in vivo mechanical inputs, and absence of endocardial cues.
      Application of immunofluorescence techniques to the study of developing mouse
      heart is desirable but more technically challenging, and methods often lack
      sufficient sensitivity and resolution to visualize sarcomeres in the early stages
      of heart development. Here, we describe a robust and reproducible method to co
      immunostain multiple proteins or to co-visualize a fluorescent protein with
      immunofluorescent staining in the embryonic mouse heart and use this method to
      analyze developing myofibrils, intercalated discs, and costameres. This method
      can be further applied to assess cardiomyocyte structural changes caused by
      mutations that lead to developmental heart defects. 

PMID- 25866998
TI  - Surface roughness and bond strength of zirconia posts to a resin cement after
      various surface pretreatments.
AB  - OBJECTIVE: The purpose of this study was to investigate the influence of post
      surface conditioning methods on the surface roughness and microtensile bond
      strength (MUTBS) of zirconia posts to a resin cement. BACKGROUND DATA: Debonding
      at the post-adhesive interface is a major problem for zirconia posts. METHODS: A
      total of 25 zirconia posts (n=5) were prepared as follows: untreated (control,
      group C), airborne-particle abraded (group AA), silica coated (group SC), Nd:YAG
      laser irradiated (group N), and Er:YAG laser irradiated (group E). Prior to
      application of a dual-cured resin cement on the posts, roughness values of the
      post surfaces were detected with a profilometer. Specimens were then sectioned to
      obtain rectangular sticks for MUTBS. After sticks were stored in distilled water
      at 37 degrees C for 24 h, MUTBS values were determined in a universal testing
      machine at a crosshead speed of 1 mm/min until failure. Furthermore, scanning
      electron microscopic (SEM) analysis was performed for one specimen of each group
      to evaluate the post surface morphology. One-way ANOVA and post-hoc comparison
      tests (alpha=0.05) were performed on all data. RESULTS: All surface treatment
      groups demonstrated significant higher MUTBS values than the control group
      (p<0.001). The highest mean force value was observed in group SC. In addition,
      similar bond strength results were detected between group SC and group E
      (p=0.669). None of treatment groups resulted in significant improvement in
      roughness values of the post (p<0.05), except group N. CONCLUSIONS: All surface
      treatments were found to be effective methods to achieve a durable bond between
      zirconia posts to resin cement.

PMID- 25866999
TI  - Predictive Risk of Radiation Induced Cerebral Necrosis in Pediatric Brain Cancer
      Patients after VMAT Versus Proton Therapy.
AB  - Cancer of the brain and central nervous system (CNS) is the second most common of
      all pediatric cancers. Treatment of many of these cancers includes radiation
      therapy of which radiation induced cerebral necrosis (RICN) can be a severe and
      potentially devastating side effect. Risk factors for RICN include brain volume
      irradiated, the dose given per fraction and total dose. Thirteen pediatric
      patients were selected for this study to determine the difference in predicted
      risk of RICN when treating with volumetric modulated arc therapy (VMAT) compared
      to passively scattered proton therapy (PSPT) and intensity modulated proton
      therapy (IMPT). Plans were compared on the basis of dosimetric endpoints in the
      planned treatment volume (PTV) and brain and a radiobiological endpoint of RICN
      calculated using the Lyman-Kutcher-Burman probit model. Uncertainty tests were
      performed to determine if the predicted risk of necrosis was sensitive to
      positional errors, proton range errors and selection of risk models. Both PSPT
      and IMPT plans resulted in a significant increase in the maximum dose to the
      brain, a significant reduction in the total brain volume irradiated to low doses,
      and a significant lower predicted risk of necrosis compared with the VMAT plans.
      The findings of this study were upheld by the uncertainty analysis. 

PMID- 25867000
TI  - Towards effective and efficient patient-specific quality assurance for spot
      scanning proton therapy.
AB  - An intensity-modulated proton therapy (IMPT) patient-specific quality assurance
      (PSQA) program based on measurement alone can be very time consuming due to the
      highly modulated dose distributions of IMPT fields. Incorporating independent
      dose calculation and treatment log file analysis could reduce the time required
      for measurements. In this article, we summarize our effort to develop an
      efficient and effective PSQA program that consists of three components:
      measurements, independent dose calculation, and analysis of patient-specific
      treatment delivery log files. Measurements included two-dimensional (2D)
      measurements using an ionization chamber array detector for each field delivered
      at the planned gantry angles with the electronic medical record (EMR) system in
      the QA mode and the accelerator control system (ACS) in the treatment mode, and
      additional measurements at depths for each field with the ACS in physics mode and
      without the EMR system. Dose distributions for each field in a water phantom were
      calculated independently using a recently developed in-house pencil beam
      algorithm and compared with those obtained using the treatment planning system
      (TPS). The treatment log file for each field was analyzed in terms of deviations
      in delivered spot positions from their planned positions using various
      statistical methods. Using this improved PSQA program, we were able to verify the
      integrity of the data transfer from the TPS to the EMR to the ACS, the dose
      calculation of the TPS, and the treatment delivery, including the dose delivered
      and spot positions. On the basis of this experience, we estimate that the in-room
      measurement time required for each complex IMPT case (e.g., a patient receiving
      bilateral IMPT for head and neck cancer) is less than 1 h using the improved PSQA
      program. Our experience demonstrates that it is possible to develop an efficient
      and effective PSQA program for IMPT with the equipment and resources available in
      the clinic. 

PMID- 25867002
TI  - Impact of Continuous Positive Airway Pressure Treatment on Leptin Levels in
      Patients with Obstructive Sleep Apnea Syndrome.
AB  - BACKGROUND: There is growing evidence that leptin regulation is altered in
      obstructive sleep apnea syndrome (OSAS). Several potential mechanisms have been
      purported to explain how sleep apnea may alter leptin levels. We investigated
      whether repeated apneas, hypoxia, or excessive daytime sleepiness influenced the
      levels of leptin in OSAS patients. We also evaluated whether a 3-month continuous
      positive airway pressure (CPAP) treatment affected leptin levels in patients.
      METHODS: Randomly selected 31 untreated, otherwise healthy male, overweight [body
      mass index (BMI) >25 kg/m(2)] obstructive sleep apnea syndrome (OSAS) patients
      [apnea-hypopnea index (AHI) >=15] and 25 control (AHI <5) were included in this
      study. To confirm the diagnosis, all subjects underwent standard polysomnography.
      Serum samples were taken at 07:00-08:00 a.m. after overnight fasting. The OSAS
      patients that had regular CPAP treatment (n=26) were re-evaulated 3 months later.
      RESULTS: Leptin levels (50.5+/-17.5 grams/L in OSAS and 56.3+/-25.5 grams/L in
      controls) and lipid profiles (TC, TGs, HDL-C, and LDL-C) between patient and
      control groups did not differ (P>0.05). Leptin levels were not correlated with
      the AHI, oxygen saturation, or excessive daytime sleepiness. CPAP treatment did
      not significantly change the (BMI), waist and neck circumference, or leptin
      levels in OSAS patients. Furthermore, we found no correlation between the
      decrease in serum leptin levels and parameters that were improved by CPAP
      treatment. CONCLUSION: Leptin levels and lipid profile of overweight subjects
      with and without OSAS were not different, and our results suggest that OSAS
      related parameters and CPAP treatment do not play a significant role in the serum
      leptin levels.

PMID- 25867001
TI  - PP2A: The Wolf in Sheep's Clothing?
AB  - Protein Phosphatase 2A (PP2A) is a major serine/threonine phosphatase in cells.
      It consists of a catalytic subunit (C), a structural subunit (A), and a
      regulatory/variable B-type subunit. PP2A has a critical role to play in
      homeostasis where its predominant function is as a phosphatase that regulates the
      major cell signaling pathways in cells. Changes in the assembly, activity and
      substrate specificity of the PP2A holoenzyme have a direct role in disease and
      are a major contributor to the maintenance of the transformed phenotype in
      cancer. We have learned a lot about how PP2A functions from specific mutations
      that disrupt the core assembly of PP2A and from viral proteins that target PP2A
      and inhibit its effect as a phosphatase. This prompted various studies revealing
      that restoration of PP2A activity benefits some cancer patients. However, our
      understanding of the mechanism of action of this is limited because of the
      complex nature of PP2A holoenzyme assembly and because it acts through a wide
      variety of signaling pathways. Information on PP2A is also conflicting as there
      are situations whereby inactivation of PP2A induces apoptosis in many cancer
      cells. In this review we discuss this relationship and we also address many of
      the pertinent and topical questions that relate to novel therapeutic strategies
      aimed at altering PP2A activity. 

PMID- 25867004
TI  - Effects of feeding outer bran fraction of rice on lipid accumulation and fecal
      excretion in rats.
AB  - Outer bran fraction of rice (OBFR) contains higher concentrations of crude fiber,
      gamma-oryzanol, and phytic acid compared to whole rice bran (WRB). In this study,
      we examined the effects of feeding OBFR on lipid accumulation and fecal excretion
      in rats. Twenty-one male rats at seven-week-old were divided into a control group
      and two treatment groups. The control group was fed a control diet, and the
      treatment groups were fed OBFR- or WRB-containing diet for 21 days. There was no
      significant difference in growth performance. Feeding OBFR diet increased fecal
      number and weight accompanied by increased fecal lipid content, while it did not
      affect mRNA expressions encoding lipid metabolism-related protein in liver. In
      addition, feeding OBFR-diet decreased the abdominal fat tissue weight and
      improved plasma lipid profiles, while WRB-containing diet did not affect them.
      These results suggested that feeding OBFR-diet might prevent lipid accumulation
      via enhancing fecal lipid excretion in rats. 

PMID- 25867003
TI  - Adopting Clean Fuels and Technologies on School Buses. Pollution and Health
      Impacts in Children.
AB  - RATIONALE: More than 25 million American children breathe polluted air on diesel
      school buses. Emission reduction policies exist, but the health impacts to
      individual children have not been evaluated. METHODS: Using a natural experiment,
      we characterized the exposures and health of 275 school bus riders before,
      during, and after the adoption of clean technologies and fuels between 2005 and
      2009. Air pollution was measured during 597 trips on 188 school buses. Repeated
      measures of exhaled nitric oxide (FeNO), lung function (FEV1, FVC), and
      absenteeism were also collected monthly (1,768 visits). Mixed-effects models
      longitudinally related the adoption of diesel oxidation catalysts (DOCs), closed
      crankcase ventilation systems (CCVs), ultralow-sulfur diesel (ULSD), or biodiesel
      with exposures and health. MEASUREMENTS AND MAIN RESULTS: Fine and ultrafine
      particle concentrations were 10-50% lower on buses using ULSD, DOCs, and/or CCVs.
      ULSD adoption was also associated with reduced FeNO (-16% [95% confidence
      interval (CI), -21 to -10%]), greater changes in FVC and FEV1 (0.02 [95% CI,
      0.003 to 0.05] and 0.01 [95% CI, -0.006 to 0.03] L/yr, respectively), and lower
      absenteeism (-8% [95% CI, -16.0 to -0.7%]), with stronger associations among
      patients with asthma. DOCs, and to a lesser extent CCVs, also were associated
      with improved FeNO, FVC growth, and absenteeism, but these findings were
      primarily restricted to patients with persistent asthma and were often sensitive
      to control for ULSD. No health benefits were noted for biodiesel. Extrapolating
      to the U.S. population, changed fuel/technologies likely reduced absenteeism by
      more than 14 million/yr. CONCLUSIONS: National and local diesel policies appear
      to have reduced children's exposures and improved health.

PMID- 25867005
TI  - High intensity and reduced volume training attenuates stress and recovery levels
      in elite swimmers.
AB  - This study investigated the effect of increased high-intensity interval training
      (HIT) at the expense of total training volume on the stress and recovery levels
      of elite swimmers. Forty-one elite swimmers participated in the study and were
      randomly assigned to either a HIT or a control group (CON). Eleven swimmers did
      not complete the questionnaires. For 12 weeks both groups trained ~12 h per week.
      The amount of HIT was ~5 h vs. 1 h, and total distance was ~17 km vs. ~35 km per
      week for HIT and CON, respectively. HIT was performed as 6-10 * 10-30 s maximal
      effort interspersed by 2-4 min of rest. The Recovery Stress Questionnaire - Sport
      was used to measure the swimmers' stress and recovery levels. After the 12 week
      intervention, the general stress level was 16.6% (2.6-30.7%; mean and 95% CI)
      lower and the general recovery level was 6.5% (0.7-12.4%) higher in HIT compared
      to the CON, after adjusting for baseline values. No significant effects could be
      observed in sports-specific stress or sports-specific recovery. The results
      indicate that increasing training intensity and reducing training volume for 12
      weeks can reduce general stress and increase general recovery levels in
      competitive swimmers. 

PMID- 25867006
TI  - Crowd-Sourced Assessment of Technical Skills: Differentiating Animate Surgical
      Skill Through the Wisdom of Crowds.
AB  - BACKGROUND: Objective quantification of surgical skill is imperative as we enter
      a healthcare environment of quality improvement and performance-based
      reimbursement. The gold standard tools are infrequently used due to time
      intensiveness, cost inefficiency, and lack of standard practices. We hypothesized
      that valid performance scores of surgical skill can be obtained through
      crowdsourcing. METHODS: Twelve surgeons of varying robotic surgical experience
      performed live porcine robot-assisted urinary bladder closures. Blinded video
      recorded performances were scored by expert surgeon graders and by Amazon's
      Mechanical Turk crowdsourcing crowd workers using the Global Evaluative
      Assessment of Robotic Skills tool assessing five technical skills domains. Seven
      expert graders and 50 unique Mechanical Turkers (each paid $0.75/survey)
      evaluated each video. Global assessment scores were analyzed for correlation and
      agreement. RESULTS: Six hundred Mechanical Turkers completed the surveys in less
      than 5 hours, while seven surgeon graders took 14 days. The duration of video
      clips ranged from 2 to 11 minutes. The correlation coefficient between the
      Turkers' and expert graders' scores was 0.95 and Cronbach's Alpha was 0.93. Inter
      rater reliability among the surgeon graders was 0.89. CONCLUSION: Crowdsourcing
      surgical skills assessment yielded rapid inexpensive agreement with global
      performance scores given by expert surgeon graders. The crowdsourcing method may
      provide surgical educators and medical institutions with a boundless number of
      procedural skills assessors to efficiently quantify technical skills for use in
      trainee advancement and hospital quality improvement.

PMID- 25867007
TI  - Catalytic two-electron reduction of dioxygen by ferrocene derivatives with
      manganese(V) corroles.
AB  - Electron transfer from octamethylferrocene (Me8Fc) to the manganese(V)
      imidocorrole complex (tpfc)Mn(V)(NAr) [tpfc = 5,10,15
      tris(pentafluorophenyl)corrole; Ar = 2,6-Cl2C6H3] proceeds efficiently to give an
      octamethylferrocenium ion (Me8Fc(+)) and [(tpfc)Mn(IV)(NAr)](-) in acetonitrile
      (MeCN) at 298 K. Upon the addition of trifluoroacetic acid (TFA), further
      reduction of [(tpfc)Mn(IV)(NAr)](-) by Me8Fc gives (tpfc)Mn(III) and ArNH2 in
      deaerated MeCN. TFA also results in hydrolysis of (tpfc)Mn(V)(NAr) with residual
      water to produce a protonated manganese(V) oxocorrole complex
      ([(tpfc)Mn(V)(OH)](+)) in deaerated MeCN. [(tpfc)Mn(V)(OH)](+) is rapidly reduced
      by 2 equiv of Me8Fc in the presence of TFA to give (tpfc)Mn(III) in deaerated
      MeCN. In the presence of dioxygen (O2), (tpfc)Mn(III) catalyzes the two-electron
      reduction of O2 by Me8Fc with TFA in MeCN to produce H2O2 and Me8Fc(+). The rate
      of formation of Me8Fc(+) in the catalytic reduction of O2 follows zeroth-order
      kinetics with respect to the concentrations of Me8Fc and TFA, whereas the rate
      increases linearly with increasing concentrations of (tpfc)Mn(V)(NAr) and O2.
      These kinetic dependencies are consistent with the rate-determining step being
      electron transfer from (tpfc)Mn(III) to O2, followed by further proton-coupled
      electron transfer from Me8Fc to produce H2O2 and [(tpfc)Mn(IV)](+). Rapid
      electron transfer from Me8Fc to [(tpfc)Mn(IV)](+) regenerates (tpfc)Mn(III),
      completing the catalytic cycle. Thus, catalytic two-electron reduction of O2 by
      Me8Fc with (tpfc)Mn(V)(NAr) as a catalyst precursor proceeds via a Mn(III)/Mn(IV)
      redox cycle. 

PMID- 25867008
TI  - Selective Formation of a Trisubstituted Alkene Motif by trans
      Hydrostannation/Stille Coupling: Application to the Total Synthesis and Late
      Stage Modification of 5,6-Dihydrocineromycin B.
AB  - Countless natural products of polyketide origin have an E-configured 2-methyl-but
      2-en-1-ol substructure. An unconventional entry into this important motif was
      developed as part of a concise total synthesis of 5,6-dihydrocineromycin B. The
      choice of this particular target was inspired by a recent study, which suggested
      that the cineromycin family of antibiotics might have overlooked lead qualities,
      although our biodata do not necessarily support this view. The new approach
      consists of a sequence of alkyne metathesis followed by a hydroxy-directed trans
      hydrostannation and a largely unprecedented methyl-Stille coupling. The excellent
      yield and remarkable selectivity with which the signature trisubstituted alkene
      site of the target was procured is noteworthy considering the rather poor outcome
      of a classical ring-closing metathesis reaction. Moreover, the unorthodox
      ruthenium-catalyzed trans-hydrostannation is shown to be a versatile handle for
      diversity-oriented synthesis. 

PMID- 25867009
TI  - The interaction of cortico-spinal pathways and sacral sphincter reflexes in
      subjects with incomplete spinal cord injury: a pilot study.
AB  - AIMS: To reveal the effectiveness of corticospinal drive in facilitating the
      pudendal reflex in the anal sphincter muscle, as a surrogate marker for the
      urethral sphincter, in incomplete spinal cord injury (iSCI). METHODS: Three
      neurologically normal subjects and twenty-six subjects with incomplete, supra
      sacral spinal cord injuries and symptoms of a neuropathic bladder were recruited.
      Incontinence was assessed using the International Consultation on Incontinence
      Modular Questionnaire (ICIQ). Electromyographic activity of the external anal
      sphincter was recorded. The pudendo-anal reflex (PAR) was elicited by electrical
      stimulation of the dorsal penile nerve (DPN). Motor cortical excitation was
      achieved using transcranial magnetic stimulation (TMS). RESULTS: Preliminary
      findings in normal and iSCI subjects showed facilitation of the PAR by prior TMS
      with an optimal interval of 20-40 msec. Of 23 iSCI subjects, 12 showed
      facilitation to TMS applied 30 msec before DPN stimulation. Eight of the 12, and
      a further five iSCI subjects, had an anal sphincter MEP in response to TMS alone.
      There was a weak tendency (r(2) = 0.22, P = 0.03) for those with higher ICIQ
      values to have larger PAR responses but no significant difference in ICIQ scores
      between those with (ICIQ = 4.9 +/- 4.0 mean +/- SD) and those without (ICIQ = 7.2
      +/- 4.7) cortical facilitation of the PAR. CONCLUSIONS: Cortical TMS was
      effective in facilitating the PAR in some iSCI subjects. The presence of cortical
      facilitation of the PAR was not related to the degree of urinary continence.

PMID- 25867011
TI  - Activation of Methane and Carbon Dioxide Mediated by Transition-Metal Doped
      Magnesium Oxide Clusters [MMgO](+/0/-) (M=Sc-Zn).
AB  - Mission: impossible? DFT calculations show that the trends in the thermochemistry
      are very different for the activation of CO2 and CH4 mediated by transition-metal
      doped magnesium oxide clusters [MMgO](+/0/-) (M=Sc-Zn). Thus, seeking a "simple"
      reagent to simultaneously mediate activation and coupling of CH4 and CO2 with
      high efficiency seems extremely daunting, if not impossible. 

PMID- 25867010
TI  - Techniques for the analysis of extracellular vesicles using flow cytometry.
AB  - Extracellular Vesicles (EVs) are small, membrane-derived vesicles found in bodily
      fluids that are highly involved in cell-cell communication and help regulate a
      diverse range of biological processes. Analysis of EVs using flow cytometry (FCM)
      has been notoriously difficult due to their small size and lack of discrete
      populations positive for markers of interest. Methods for EV analysis, while
      considerably improved over the last decade, are still a work in progress.
      Unfortunately, there is no one-size-fits-all protocol, and several aspects must
      be considered when determining the most appropriate method to use. Presented here
      are several different techniques for processing EVs and two protocols for
      analyzing EVs using either individual detection or a bead-based approach. The
      methods described here will assist with eliminating the antibody aggregates
      commonly found in commercial preparations, increasing signal-to-noise ratio, and
      setting gates in a rational fashion that minimizes detection of background
      fluorescence. The first protocol uses an individual detection method that is
      especially well suited for analyzing a high volume of clinical samples, while the
      second protocol uses a bead-based approach to capture and detect smaller EVs and
      exosomes. 

PMID- 25867012
TI  - Salvage surgery for locally recurrent oropharyngeal cancer.
AB  - BACKGROUND: There are limited data on whether recurrent human papillomavirus
      (HPV)-associated oropharyngeal squamous cell carcinoma (SCC) is associated with
      higher surgical salvage rates. The purpose of this study was to determine the
      success rate of salvage surgery for locally recurrent oropharyngeal cancer and
      factors influencing the outcome, including p16 status. METHODS: All patients who
      underwent salvage surgery for locally recurrent or persistent oropharyngeal
      cancer after (chemo)radiotherapy between 2000 and 2012 were included. The Kaplan
      Meier analysis was used to determine overall survival (OS) and recurrence-free
      survival (RFS). Univariable analysis was performed using Cox proportional hazards
      regression. RESULTS: Thirty-four patients underwent salvage surgery. Five
      patients (14.7%) were tracheostomy dependent and 22 (64.7%) were gastrostomy tube
      dependent after salvage surgery. Postoperative complications occurred in 15
      patients. RFS after salvage surgery was 28% and 19% at 3 and 5 years,
      respectively. The presence of nodal disease at the time of local recurrence,
      close or positive margins, and lymphovascular invasion were the only factors
      associated with worse survival on univariable analysis. HPV status based on p16
      testing was not associated with either OS or RFS. CONCLUSION: Surgical salvage
      for oropharyngeal SCC after failure of radiotherapy (+/- chemotherapy) is
      feasible. Patients who may benefit from surgery include those without regional
      recurrence and/or those in whom negative margins can be obtained. However,
      patients may be tracheotomy or gastrostomy tube dependent. The p16 status did not
      seem to have prognostic impact in the salvage setting; however, larger series are
      required to assess this relationship. (c) 2015 Wiley Periodicals, Inc. Head Neck
      38: E658-E664, 2016.

PMID- 25867013
TI  - Lost voices.

PMID- 25867015
TI  - Chemical profile of major taste- and health-related compounds of Oblacinska sour
      cherry.
AB  - BACKGROUND: Oblacinska sour cherry, an autochthonous cultivar, is the most
      planted cultivar in Serbian commercial orchards. Owing to its long cultivation
      under different agro-ecological conditions, it is a mixture of different clones.
      To obtain comprehensive information on Oblacinska sour cherry fruit, the total
      carbohydrate composition, total phenolic content, total anthocyanin content,
      antioxidant activity and polyphenolic profiles of 39 clones were investigated.
      RESULTS: Fructose was found to be the dominant sugar, followed by glucose,
      sorbitol and sucrose. Rutin and chlorogenic acid were the most abundant
      polyphenols. Some clones contained pinobanksin, hesperetin and galangin, which,
      to best knowledge, is the first time these compounds have been reported in sour
      cherry fruit. CONCLUSION: The data obtained showed huge variation within the
      germplasm studied, confirming the fact that Oblacinska sour cherry is not a
      cultivar but a population.

PMID- 25867014
TI  - Natural genetic variation in Arabidopsis thaliana defense metabolism genes
      modulates field fitness.
AB  - Natural populations persist in complex environments, where biotic stressors, such
      as pathogen and insect communities, fluctuate temporally and spatially. These
      shifting biotic pressures generate heterogeneous selective forces that can
      maintain standing natural variation within a species. To directly test if genes
      containing causal variation for the Arabidopsis thaliana defensive compounds,
      glucosinolates (GSL) control field fitness and are therefore subject to natural
      selection, we conducted a multi-year field trial using lines that vary in only
      specific causal genes. Interestingly, we found that variation in these naturally
      polymorphic GSL genes affected fitness in each of our environments but the
      pattern fluctuated such that highly fit genotypes in one trial displayed lower
      fitness in another and that no GSL genotype or genotypes consistently out
      performed the others. This was true both across locations and within the same
      location across years. These results indicate that environmental heterogeneity
      may contribute to the maintenance of GSL variation observed within Arabidopsis
      thaliana. 

PMID- 25867016
TI  - Experimental and imaging techniques for examining fibrin clot structures in
      normal and diseased states.
AB  - Fibrin is an extracellular matrix protein that is responsible for maintaining the
      structural integrity of blood clots. Much research has been done on fibrin in the
      past years to include the investigation of synthesis, structure-function, and
      lysis of clots. However, there is still much unknown about the morphological and
      structural features of clots that ensue from patients with disease. In this
      research study, experimental techniques are presented that allow for the
      examination of morphological differences of abnormal clot structures due to
      diseased states such as diabetes and sickle cell anemia. Our study focuses on the
      preparation and evaluation of fibrin clots in order to assess morphological
      differences using various experimental assays and confocal microscopy. In
      addition, a method is also described that allows for continuous, real-time
      calculation of lysis rates in fibrin clots. The techniques described herein are
      important for researchers and clinicians seeking to elucidate comorbid thrombotic
      pathologies such as myocardial infarctions, ischemic heart disease, and strokes
      in patients with diabetes or sickle cell disease. 

PMID- 25867019
TI  - A highly soluble gadofullerene salt and its magnetic properties.
AB  - A kind of Gd@C82 salt, Gd@C82/TBPA, was prepared through chemical oxidation. The
      Gd@C82/TBPA salt was characterized as being paramagnetic with an effective
      magnetic moment of 9.68MUB. The Gd@C82/TBPA salt dissolves in many organic
      solvents and its high solubility will make it more applicable for use as a
      magnetic material. 

PMID- 25867018
TI  - A cost-effectiveness analysis of human papillomavirus vaccination of boys for the
      prevention of oropharyngeal cancer.
AB  - BACKGROUND: Many western countries have established female human papillomavirus
      (HPV) vaccination programs for the prevention of cervical cancer. The
      quadrivalent HPV vaccine (HPV4) has proven efficacy against additional HPV
      related disease in both sexes, but the cost effectiveness of male HPV vaccination
      remains controversial. To assess the cost effectiveness of male HPV vaccination
      in Canada with respect to oropharyngeal cancer (OPC), the authors performed a
      preliminary cost-effectiveness analysis. METHODS: After an extensive literature
      review regarding HPV-related OPC in Canadian males, health care costs and
      clinical effectiveness estimates were obtained. A Markov model was used to
      compare the potential costs and effectiveness of HPV4 versus no vaccination among
      boys aged 12 years. A theoretical cohort based on a Canadian population of
      192,940 boys aged 12 years in 2012 was assumed to apply the model. A 3-month
      cycle length was used with a "lifetime" time horizon. The outcome of the analysis
      was the incremental cost per quality-adjusted life-year (QALY). Sensitivity
      analyses were conducted on variables, including the vaccine uptake rate and
      vaccine efficacy. RESULTS: Assuming 99% vaccine efficacy and 70% uptake, HPV4
      produced 0.05 more QALYs and saved $145 Canadian dollars (CAD) per individual
      compared with no vaccine (QALYs and costs were discounted at 5% per year).
      Assuming 50% vaccine efficacy and 50% uptake, HPV4 produced 0.023 more QALYs and
      saved $42 CAD. The results indicated that HPV4 in males may potentially save
      between $8 and $28 million CAD for the theoretical cohort of 192,940 over its
      lifetime. CONCLUSIONS: On the basis of this model, HPV vaccination for boys aged
      12 years may be a cost-effective strategy for the prevention of OPC in Canada.

PMID- 25867017
TI  - Forward genetics screens using macrophages to identify Toxoplasma gondii genes
      important for resistance to IFN-gamma-dependent cell autonomous immunity.
AB  - Toxoplasma gondii, the causative agent of toxoplasmosis, is an obligate
      intracellular protozoan pathogen. The parasite invades and replicates within
      virtually any warm blooded vertebrate cell type. During parasite invasion of a
      host cell, the parasite creates a parasitophorous vacuole (PV) that originates
      from the host cell membrane independent of phagocytosis within which the parasite
      replicates. While IFN-dependent-innate and cell mediated immunity is important
      for eventual control of infection, innate immune cells, including neutrophils,
      monocytes and dendritic cells, can also serve as vehicles for systemic
      dissemination of the parasite early in infection. An approach is described that
      utilizes the host innate immune response, in this case macrophages, in a forward
      genetic screen to identify parasite mutants with a fitness defect in infected
      macrophages following activation but normal invasion and replication in naive
      macrophages. Thus, the screen isolates parasite mutants that have a specific
      defect in their ability to resist the effects of macrophage activation. The paper
      describes two broad phenotypes of mutant parasites following activation of
      infected macrophages: parasite stasis versus parasite degradation, often in
      amorphous vacuoles. The parasite mutants are then analyzed to identify the
      responsible parasite genes specifically important for resistance to induced
      mediators of cell autonomous immunity. The paper presents a general approach for
      the forward genetics screen that, in theory, can be modified to target parasite
      genes important for resistance to specific antimicrobial mediators. It also
      describes an approach to evaluate the specific macrophage antimicrobial mediators
      to which the parasite mutant is susceptible. Activation of infected macrophages
      can also promote parasite differentiation from the tachyzoite to bradyzoite stage
      that maintains chronic infection. Therefore, methodology is presented to evaluate
      the importance of the identified parasite gene to establishment of chronic
      infection. 

PMID- 25867021
TI  - A challenge and an opportunity.

PMID- 25867020
TI  - Aspartate-modified doxorubicin on its N-terminal increases drug accumulation in
      LAT1-overexpressing tumors.
AB  - L-type amino acid transporter 1 (LAT1), overexpressed on the membrane of various
      tumor cells, is a potential target for tumor-targeting therapy. This study aimed
      to develop a LAT1-mediated chemotherapeutic agent. We screened doxorubicin
      modified by seven different large neutral amino acids. The aspartate-modified
      doxorubicin (Asp-DOX) showed the highest affinity (Km = 41.423 MUmol/L) to LAT1.
      Aspartate was attached to the N-terminal of DOX by the amide bond with a free
      carboxyl and a free amino group on the alpha-carbon atom of the Asp residue. The
      product Asp-DOX was characterized by HPLC/MS. In vitro, Asp-DOX exerted stronger
      inhibition on the cancer cells overexpressing LAT1 and the uptake of Asp-DOX was
      approximately 3.5-fold higher than that of DOX in HepG2 cells. Pharmacokinetic
      data also showed that Asp-DOX was expressed over a longer circulation time (t1/2
      = 49.14 min) in the blood compared to DOX alone (t1/2 = 15.12 min). In HepG2 and
      HCT116 tumor-bearing mice, Asp-DOX achieved 3.1-fold and 6.4-fold accumulation of
      drugs in tumor tissue, respectively, than those of the unmodified DOX. More
      importantly, treatment of tumor-bearing mice with Asp-DOX showed a significantly
      stronger inhibition of tumor growth than mice treated with free DOX in HepG2
      tumor models. Furthermore, after Asp modification, Asp-DOX avoided MDR mediated
      by P-glycoprotein. These results suggested that the Asp-DOX modified drug may
      provide a new treatment strategy for tumors that overexpress LAT1 and MDR1.

PMID- 25867022
TI  - Screening for hazardous alcohol use among university students using individual
      questions from the Alcohol Use Disorders Identification Test-Consumption.
AB  - INTRODUCTION AND AIMS: Abbreviated versions of the Alcohol Use Disorders
      Identification Test-Consumption (AUDIT-C) instrument have not been investigated
      among students. We compared a modified second item (AUDIT-2*) (typical quantity
      per occasion as the number of drinks, rather than categorical responses) and the
      third item (AUDIT-3) (heavy episodic drinking frequency) with AUDIT-C scores and
      described their associations with sociodemographic variables. DESIGN AND METHODS:
      We analysed cross-sectional data from the 2011 baseline of the Graduate
      Longitudinal Study New Zealand, including respondents aged up to 25 years (n =
      5082, response rate 65%). Hazardous drinking was defined as an AUDIT-C score of
      seven or greater for men and five or greater for women. We calculated the area
      under receiver operating characteristic curves, sensitivities, specificities, and
      positive and negative predictive values for the AUDIT-2* and AUDIT-3. Odds ratios
      and 95% confidence intervals were calculated to describe the associations between
      drinking patterns and sociodemographic factors. RESULTS: Based on the sex
      specific AUDIT-C cut-points, 36% of participants reported drinking at hazardous
      levels. For the AUDIT-2*, the best combination of sensitivity and specificity was
      obtained for a cut-point of five standard drinks. The best cut-point for the
      AUDIT-3 was for monthly heavy episodic drinking. Positive and negative predictive
      values were above 0.80 for both cut-points. Consumption was associated with age,
      degree level, domestic/international status, accommodation type, relationship
      status and employment. DISCUSSION AND CONCLUSIONS: The AUDIT-2* and the AUDIT-3
      appear to be promising standalone screening items for detecting hazardous
      drinking in this population of heavy-drinking students. [Blank M-L, Connor J,
      Gray A, Tustin K. Screening for hazardous alcohol use among university students
      using individual questions from the Alcohol Use Disorders Identification Test
      Consumption. Drug Alcohol Rev 2015;34:540-8].

PMID- 25867023
TI  - Balloon Eustachian tuboplasty: a retrospective cohort study.
AB  - BACKGROUND: Eustachian tube dysfunction is regarded as a 'black box' term,
      reflecting a spectrum of dysfunction. The key to its diagnosis and management is
      in identifying the aetiology and exact pathophysiology of the dysfunction.
      DESIGN: We present our retrospective 5-year results for the technique of
      transnasal endoscopic balloon dilatation of the cartilaginous part of the
      Eustachian tube, balloon Eustachian tuboplasty (BET). The indication for
      treatment is chronic obstructive Eustachian tube dysfunction. MAIN OUTCOME
      MEASURES: Preoperatively, the Eustachian tube score (ETS) was obtained by a
      clinico-objective assessment involving tubomanometry (TMM) and reported patient
      symptom. The measurements were repeated 1, 2, 3, 4 and 5 years postoperatively.
      SETTING: Tertiary referral centre. PARTICIPANTS: A total of 622 patients (1076
      ears) were treated with BET. RESULTS: One year after treatment, the Eustachian
      tube score improved from 3.13 (+/- 2.47 SD) to 5.75 (+/- 2.76 SD). The Eustachian
      tube score improved significantly in 73% of ears. The average Eustachian tube
      score 2 years after treatment improved from 2.65 (+/- 2.89 SD) to 6.26 (+/- 3.07
      SD). In 82% of patients, the Eustachian tube score improved significantly at 5
      years. The subjective satisfaction of the patients was approximately 80%.
      CONCLUSIONS: Our long-term results suggest that BET is a safe and feasible
      treatment for chronic obstructive Eustachian tube dysfunction with a success rate
      of more than 70%. This study has important implications for other Eustachian tube
      related clinical entities, such as glue ear management (adults and children),
      continued grommet insertion and tympanomastoid surgery outcomes.

PMID- 25867024
TI  - Role of ALADIN in human adrenocortical cells for oxidative stress response and
      steroidogenesis.
AB  - Triple A syndrome is caused by mutations in AAAS encoding the protein ALADIN. We
      investigated the role of ALADIN in the human adrenocortical cell line NCI-H295R1
      by either over-expression or down-regulation of ALADIN. Our findings indicate
      that AAAS knock-down induces a down-regulation of genes coding for type II
      microsomal cytochrome P450 hydroxylases CYP17A1 and CYP21A2 and their electron
      donor enzyme cytochrome P450 oxidoreductase, thereby decreasing biosynthesis of
      precursor metabolites required for glucocorticoid and androgen production.
      Furthermore we demonstrate that ALADIN deficiency leads to increased
      susceptibility to oxidative stress and alteration in redox homeostasis after
      paraquat treatment. Finally, we show significantly impaired nuclear import of DNA
      ligase 1, aprataxin and ferritin heavy chain 1 in ALADIN knock-down cells. We
      conclude that down-regulating ALADIN results in decreased oxidative stress
      response leading to alteration in steroidogenesis, highlighting our knock-down
      cell model as an important in-vitro tool for studying the adrenal phenotype in
      triple A syndrome. 

PMID- 25867025
TI  - GST M1-T1 null allele frequency patterns in geographically assorted human
      populations: a phylogenetic approach.
AB  - Genetic diversity in drug metabolism and disposition is mainly considered as the
      outcome of the inter-individual genetic variation in polymorphism of drug
      xenobiotic metabolizing enzyme (XME). Among the XMEs, glutathione-S-transferases
      (GST) gene loci are an important candidate for the investigation of diversity in
      allele frequency, as the deletion mutations in GST M1 and T1 genotypes are
      associated with various cancers and genetic disorders of all major Population
      Affiliations (PAs). Therefore, the present population based phylogenetic study
      was focused to uncover the frequency distribution pattern in GST M1 and T1 null
      genotypes among 45 Geographically Assorted Human Populations (GAHPs). The
      frequency distribution pattern for GST M1 and T1 null alleles have been detected
      in this study using the data derived from literatures representing 44 populations
      affiliated to Africa, Asia, Europe, South America and the genome of PA from
      Gujarat, a region in western India. Allele frequency counting for Gujarat PA and
      scattered plot analysis for geographical distribution among the PAs were
      performed in SPSS-21. The GST M1 and GST T1 null allele frequencies patterns of
      the PAs were computed in Seqboot, Gendist program of Phylip software package
      (3.69 versions) and Unweighted Pair Group method with Arithmetic Mean in Mega-6
      software. Allele frequencies from South African Xhosa tribe, East African
      Zimbabwe, East African Ethiopia, North African Egypt, Caucasian, South Asian
      Afghanistan and South Indian Andhra Pradesh have been identified as the probable
      seven patterns among the 45 GAHPs investigated in this study for GST M1-T1 null
      genotypes. The patternized null allele frequencies demonstrated in this study for
      the first time addresses the missing link in GST M1-T1 null allele frequencies
      among GAHPs. 

PMID- 25867026
TI  - Metformin inhibits growth of human glioblastoma cells and enhances therapeutic
      response.
AB  - High-grade gliomas, glioblastomas (GB), are refractory to conventional treatment
      combining surgery, chemotherapy, mainly temozolomide, and radiotherapy. This
      highlights an urgent need to develop novel therapies and increase the efficacy of
      radio/chemotherapy for these very aggressive and malignant brain tumors.
      Recently, tumor metabolism became an interesting potential therapeutic target in
      various cancers. Accordingly, combining drugs targeting cell metabolism with
      appropriate chemotherapeutic agents or radiotherapy has become attractive. In
      light of these perspectives, we were particularly interested in the anti-cancer
      properties of a biguanide molecule used for type 2 diabetes treatment, metformin.
      In our present work, we demonstrate that metformin decreases mitochondrial
      dependent ATP production and oxygen consumption and increases lactate and
      glycolytic ATP production. We show that metformin induces decreased
      proliferation, cell cycle arrest, autophagy, apoptosis and cell death in vitro
      with a concomitant activation of AMPK, Redd1 and inhibition of the mTOR pathway.
      Cell sensitivity to metformin also depends on the genetic and mutational
      backgrounds of the different GB cells used in this study, particularly their PTEN
      status. Interestingly, knockdown of AMPK and Redd1 with siRNA partially, but
      incompletely, abrogates the induction of apoptosis by metformin suggesting both
      AMPK/Redd1-dependent and -independent effects. However, the primary determinant
      of the effect of metformin on cell growth is the genetic and mutational
      backgrounds of the glioma cells. We further demonstrate that metformin treatment
      in combination with temozolomide and/or irradiation induces a synergistic anti
      tumoral response in glioma cell lines. Xenografts performed in nude mice
      demonstrate in vivo that metformin delays tumor growth. As current treatments for
      GB commonly fail to cure, the need for more effective therapeutic options is
      overwhelming. Based on these results, metformin could represent a potential
      enhancer of the cytotoxic effects of temozolomide and/or radiotherapy. 

PMID- 25867028
TI  - Effect of plastic film mulching on the grain filling and hormonal changes of
      maize under different irrigation conditions.
AB  - Plastic film mulching (PM) is widely utilized for maize production in China.
      However, the effect of PM on the grain yield of crops has not been established,
      and the biochemical mechanism underlying the increase or decrease in grain yield
      under PM is not yet understood. Grain filling markedly affects the grain yield.
      The objective of this study was to investigate the effects of PM on maize grain
      filling under different irrigation levels and the relationship of such effects
      with hormonal changes. In the present study, PM was compared with traditional
      nonmulching management (TN) under 220 mm, 270 mm and 320 mm irrigation amount,
      and the grain filling characters of the grains located in various parts of the
      ear and the hormonal changes in the grains were measured. The results indicated
      that at 220 mm irrigation, PM significantly increased the grain filling rate of
      the middle and basal grains and decreased the grain filling rate of the upper
      grains. At 270 mm irrigation, the PM significantly increased the grain filling
      rate of the all grains. At 320 mm irrigation, the PM only significantly increased
      the grain filling rate of the upper grains. The IAA, Z+ZR and ABA content in the
      grains was positively correlated with the grain weight and grain-filling rates;
      however, the ETH evolution rate of the grains was negatively correlated with the
      grain weight and grain-filling rates. These results show that the effect of PM on
      maize grain filling is related to the irrigation amount and that the grain
      position on the ear and the grain filling of the upper grains was more sensitive
      to PM and irrigation than were the other grains. In addition, the PM and
      irrigation regulated the balance of hormones rather than the content of
      individual hormones to affect the maize grain filling. 

PMID- 25867027
TI  - Dynamics of on-off neural firing patterns and stochastic effects near a sub
      critical Hopf bifurcation.
AB  - On-off firing patterns, in which repetition of clusters of spikes are
      interspersed with epochs of subthreshold oscillations or quiescent states, have
      been observed in various nervous systems, but the dynamics of this event remain
      unclear. Here, we report that on-off firing patterns observed in three
      experimental models (rat sciatic nerve subject to chronic constrictive injury,
      rat CA1 pyramidal neuron, and rabbit blood pressure baroreceptor) appeared as an
      alternation between quiescent state and burst containing multiple period-1 spikes
      over time. Burst and quiescent state had various durations. The interspike
      interval (ISI) series of on-off firing pattern was suggested as stochastic using
      nonlinear prediction and autocorrelation function. The resting state was changed
      to a period-1 firing pattern via on-off firing pattern as the potassium
      concentration, static pressure, or depolarization current was changed. During the
      changing process, the burst duration of on-off firing pattern increased and the
      duration of the quiescent state decreased. Bistability of a limit cycle
      corresponding to period-1 firing and a focus corresponding to resting state was
      simulated near a sub-critical Hopf bifurcation point in the deterministic Morris
      Lecar (ML) model. In the stochastic ML model, noise-induced transitions between
      the coexisting regimes formed an on-off firing pattern, which closely matched
      that observed in the experiment. In addition, noise-induced exponential change in
      the escape rate from the focus, and noise-induced coherence resonance were
      identified. The distinctions between the on-off firing pattern and stochastic
      firing patterns generated near three other types of bifurcations of equilibrium
      points, as well as other viewpoints on the dynamics of on-off firing pattern, are
      discussed. The results not only identify the on-off firing pattern as noise
      induced stochastic firing pattern near a sub-critical Hopf bifurcation point, but
      also offer practical indicators to discriminate bifurcation types and neural
      excitability types. 

PMID- 25867029
TI  - Ink-Jet Printed CMOS Electronics from Oxide Semiconductors.
AB  - Complementary metal oxide semiconductor (CMOS) technology with high
      transconductance and signal gain is mandatory for practicable digital/analog
      logic electronics. However, high performance all-oxide CMOS logics are scarcely
      reported in the literature; specifically, not at all for solution
      processed/printed transistors. As a major step toward solution-processed all
      oxide electronics, here it is shown that using a highly efficient electrolyte
      gating approach one can obtain printed and low-voltage operated oxide CMOS logics
      with high signal gain (~21 at a supply voltage of only 1.5 V) and low static
      power dissipation. 

PMID- 25867030
TI  - Clinical outcomes of cryptogenic compared with non-cryptogenic cirrhosis: A
      retrospective cohort study.
AB  - BACKGROUND AND AIM: The consequences of the association between the metabolic
      syndrome and cryptogenic cirrhosis are uncertain. We aimed to compare the
      differences in clinical outcomes between cryptogenic and non-cryptogenic
      cirrhosis. METHODS: A retrospective cohort study was conducted in a large, single
      academic center, over a 5-year duration. RESULTS: Complete data were available in
      301 patients with cirrhosis (cryptogenic n = 94, non-cryptogenic n = 207).
      Compared with non-cryptogenic cirrhosis, patients with cryptogenic cirrhosis were
      older (mean age 66.4 +/- 12.5 vs 60.7 +/- 11.3 years, P < 0.0001), had more
      females (43.6% vs 26.6%, P = 0.003), had less disease severity (Child-Pugh C 8.5%
      vs 15.9%, P = 0.042), and had a higher prevalence of the metabolic syndrome (83%
      vs 51.2%, P < 0.0001). During the 5-year period, adults with cryptogenic Child
      Pugh A cirrhosis had a longer total hospital admission duration compared with non
      cryptogenic cirrhosis (median 7.0 vs 3.0 days, P = 0.035), but this was less
      evident in patients with more advanced disease. This difference was due to a
      longer duration of hospitalization for non-liver-related morbidity (median 14.0
      days vs 8.0 days, P = 0.04), rather than liver-related morbidity (median 10.5
      days vs 8.0 days, P = 0.34), in patients with cryptogenic compared with non
      cryptogenic cirrhosis. Kaplan-Meier survival analysis showed no significant
      differences in survival between both types of cirrhosis for all grades of
      severity. CONCLUSIONS: Cryptogenic cirrhosis is associated with a longer duration
      of hospitalization compared with non-cryptogenic cirrhosis at an early stage of
      the disease. This difference is due to a greater burden of non-liver-related
      complications in the former.

PMID- 25867031
TI  - Positive psychological health and stroke risk: The benefits of emotional
      vitality.
AB  - OBJECTIVE: Stroke is a leading cause of death and disability. Various forms of
      positive psychological health (e.g., emotional vitality) are associated with
      lower risk for heart disease. However, it is unclear whether positive
      psychological health may also be beneficial for stroke risk. The purpose of the
      present study was to examine prospectively the association between emotional
      vitality and incident stroke in a nationally representative sample of 6,019
      participants in the first National Health and Nutrition Examination Survey
      Epidemiologic Follow-up Study. METHODS: Emotional vitality was assessed via self
      report at study baseline in 1971-1975. Stroke cases were identified from
      hospital/nursing home discharge reports and death certificates. Multivariate Cox
      proportional hazards regression models were used to estimate hazard ratios and
      95% confidence intervals of incident stroke associated with a 1 SD increase in
      emotional vitality scores. Models were adjusted for traditional cardiovascular
      disease risk factors and subsequently for psychological distress. RESULTS: Higher
      emotional vitality was associated with lower risk of incident stroke over a mean
      of 16.29 (SD = 4.75) years of follow-up (hazard ratio = 0.89; 95% confidence
      interval: 0.81, 0.99). Findings persisted when controlling for traditional
      cardiovascular disease risk factors and psychological distress. CONCLUSIONS:
      Higher levels of emotional vitality were prospectively associated with lower
      stroke risk in a representative sample of the U.S. POPULATION: Associations were
      independent of psychological distress. Results point to the potential importance
      of positive psychological functioning for cardiovascular health and for stroke
      prevention. (PsycINFO Database Record

PMID- 25867032
TI  - Complex Nano-objects Displaying Both Magnetic and Catalytic Properties: A Proof
      of Concept for Magnetically Induced Heterogeneous Catalysis.
AB  - Addition of Co2(Co)9 and Ru3(CO)12 on preformed monodisperse iron(0)
      nanoparticles (Fe(0) NPs) at 150  degrees C under H2 leads to monodisperse core
      shell Fe@FeCo NPs and to a thin discontinuous Ru(0) layer supported on the
      initial Fe(0) NPs. The new complex NPs were studied by state-of-the-art
      transmission electron microscopy techniques as well as X-ray diffraction,
      Mossbauer spectroscopy, and magnetic measurements. These particles display large
      heating powers (SAR) when placed in an alternating magnetic field. The
      combination of magnetic and surface catalytic properties of these novel objects
      were used to demonstrate a new concept: the possibility of performing Fischer
      Tropsch syntheses by heating the catalytic nanoparticles with an external
      alternating magnetic field. 

PMID- 25867033
TI  - Severe secondary postpartum hemorrhage: a historical cohort.
AB  - OBJECTIVES: The principal objective of our study was to describe the frequency of
      severe secondary postpartum hemorrhages (PPH). Our secondary objectives were to
      describe the different causes of PPH and to assess if the PPH etiologies varied
      by parity. METHODS: This is a historical cohort study covering the period from
      January 1, 2004, through February 13, 2013, in a level III maternity ward. Women
      were eligible if they were treated for severe secondary PPH during their
      postpartum hospitalization or were admitted for it after discharge but before the
      42nd day postpartum, regardless of the type of delivery. Women were excluded if
      they gave birth before 22 weeks of gestation or if they had experienced only an
      immediate PPH (<= 24 hours after delivery). Eligible patients were identified by
      the hospital's administrative software. Primiparas and multiparas were compared
      with Student's t test and a chi-squared or Fisher's exact test. RESULTS: The
      incidence of severe secondary PPH was 0.23 percent (n = 60/26,023). The mean time
      between delivery and PPH onset was 13.4 +/- 10.8 days. The women's mean age was
      30.4 +/- 5.7 years and their mean body mass index was 23.4 +/- 5.7 kg/m2.
      Placental retention was the cause to which these hemorrhages were most frequently
      attributed (30.0%). Subinvolution of the placental bed was noted in 13.3 percent
      of the patients, endometritis in 10.0 percent, pseudoaneurysm of the uterine
      artery in 3.3 percent, and excessively strong resumption of menses in 3.3
      percent; no cause could be determined for 16.7 percent of the cases. Neither
      clinical signs nor causes differed by parity. CONCLUSION: Secondary PPH is rare.
      Accurate diagnosis is based most often on histopathologic findings.

PMID- 25867034
TI  - Paper-based devices for isolation and characterization of extracellular vesicles.
AB  - Extracellular vesicles (EVs), membranous particles released from various types of
      cells, hold a great potential for clinical applications. They contain nucleic
      acid and protein cargo and are increasingly recognized as a means of
      intercellular communication utilized by both eukaryote and prokaryote cells.
      However, due to their small size, current protocols for isolation of EVs are
      often time consuming, cumbersome, and require large sample volumes and expensive
      equipment, such as an ultracentrifuge. To address these limitations, we developed
      a paper-based immunoaffinity platform for separating subgroups of EVs that is
      easy, efficient, and requires sample volumes as low as 10 MUl. Biological samples
      can be pipetted directly onto paper test zones that have been chemically modified
      with capture molecules that have high affinity to specific EV surface markers. We
      validate the assay by using scanning electron microscopy (SEM), paper-based
      enzyme-linked immunosorbent assays (P-ELISA), and transcriptome analysis. These
      paper-based devices will enable the study of EVs in the clinic and the research
      setting to help advance our understanding of EV functions in health and disease. 

PMID- 25867035
TI  - Effects of Beta-d-glucan on diabetic colon anastomosis.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effects of beta-D-glucan
      on the experimental diabetic rat colon anastomosis model. BACKGROUND: Beta-D
      glucan is a commonly used macrophage activator and promotes wound healing by
      increasing macrophage infiltration into the wound. The decrease in the function
      of macrophages and impaired wound healing can be observed in diabetes mellitus
      (DM). METHODS: Eighty Spraque-Dawley rats were divided into 4 groups: colon
      anastomosis (group 1); colon anastomosis + DM (group 2); colon anastomosis + beta
      D-glucan (group 3); and colon anastomosis + beta-D-glucan + DM (group 4).
      Diabetes was induced with streptozotocin (85 mg/kg), and glycemia was assessed
      before induction at days 14 and 17. Colon anastomosis was performed at day 14.
      Beta-D-glucan (100 mg/kg/day) was administered 2 days before colon anastomosis
      and given orally for 5 days. Relaparotomies were done 3 days after colon
      anastomosis, and anastomotic bursting pressures, anastomotic hydroxyproline
      levels, malondialdehyde (MDA) levels, and histopathology examinations were
      studied. RESULTS: There were no differences among groups for hydroxyproline
      levels. The mean values of anastomotic bursting pressures in group 4 were
      significantly higher than those of group 2. The mean values of MDA levels in
      group 2 were significantly lower than those of group 4. Group 2 showed a
      significant difference in the amount of necrosis, accumulation of
      polmorphonuclear cells, and edema when compared with groups 1, 3, and 4 (P <
      0.001, P < 0.002, and P < 0.001, respectively). CONCLUSION: This study indicates
      that oral administration of beta-D-glucan significantly improves the impaired
      anastomotic healing in rats with diabetes mellitus.

PMID- 25867036
TI  - Impact of an antimicrobial dressing in reducing surgical site infections in
      cardiac surgery patients.
AB  - xBxxaxcxkground. In addition to prevention guidelines already in place, the
      effectiveness of an antimicrobial dressing on the occurrence of surgical site
      infections (SSIs) among adult patients undergoing cardiac surgery was evaluated.
      METHODS: A house-wide replacement of the plain postoperative gauze dressing with
      a sterile dressing impregnated with 0.2% polyhexamethylene biguanide directly on
      the incision after closure in the operation room was performed. From May 2005 to
      March 2007, 1658 patients were enrolled in this study. Surgical site infections
      were identified using the Centers for Disease Control and Prevention standard
      criteria. RESULTS: Of the 1658 patients enrolled, 1399 patients were included in
      the analysis, 692 with the plain dressing and 707 with antimicrobial dressing.
      The overall and leg site infection rate was significantly higher in the plain
      dressing group compared to the antimicrobial group but similar in the sternal
      site. Overall, the antimicrobial dressings significantly reduced infection (OR
      0.58 [0.38-0.89]). Obesity was also a strong independent predictor of SSI
      regardless of the site of surgery. Increasing age at surgery and left ventricular
      ejection fraction of 30%-49% were also independent predictors of infection.
      CONCLUSION: The antimicrobial dressing had a positive effect by reducing the
      infection rate, especially for leg incisions using conventional open techniques,
      and could be a worthwhile addition in conjunction with a strategic program.    .

PMID- 25867037
TI  - Experimental Research on Stimulation of Wound Healing by n-3 Fatty Acids.
AB  - Objexctive. The objective of this study was to investigate the wound healing
      effects of n-3 fatty acids and to identify factors that stimulate wound healing.
      MATERIALS AND METHODS: Four-week-old male Wistar rats were subjected to full
      thickness skin wounds and assigned to 3 experimental diet groups (an n-3 fatty
      acid-fortified diet, a diet with a 1:3 ratio of n-3 to n-6 fatty acids, and an n
      6 fatty acid-fortified diet). Intergroup comparisons were conducted for the
      changes in wound areas, the number of days to wound healing, and blood cytokines,
      blood hydroxyproline, and blood chemistry test values on the day before and after
      wound healing. RESULTS: The number of days to wound healing in the n-3/n-6 fatty
      acid group (18.4 +/- 1.8 days) was significantly shorter than in the n-3 fatty
      acid-fortified diet (21.6 +/- 1.6 days) and n-6 fatty acid-fortified diet groups
      (21.9 +/- 1.8 days). This suggests that the n-3/n-6 fatty acid diet stimulates
      wound healing (P < 0.05). Changes in wound area, however, were not significantly
      different. The n-3 fatty acid-fortified diet was found to have potent
      immunopotentiating and anti-inflammatory effects in the group receiving this
      diet, as evidenced by total blood lymphocyte count and plasma levels of
      interleukin-1 beta (IL-1beta) and sialic acid on day 1 after wounding. The plasma
      hydroxyproline concentrations noted in the groups with a diet containing n-3
      fatty acids indicate that this fatty acid type stimulates wound healing.
      CONCLUSIONS: Findings suggest that n-3 fatty acids have anti-inflammatory and
      immunopotentiating effects, and are beneficial in the wound healing process,
      particularly during early inflammation.  .

PMID- 25867038
TI  - Low-frequency ultrasound debridement in patients with diabetic foot ulcers and
      osteomyelitis.
AB  - BACKGROUND: Although debridement plays a significant role in the healing of
      diabetic foot ulcers, it may delay the healing process by damaging the
      granulation tissue. In this study, the efficacy of low-frequency ultrasound (LFU)
      in chronic wound healing in diabetic foot ulcers in patients with osteomyelitis
      was evaluated. METHODS: This randomized clinical trial was conducted on 40
      patients with diabetes recruited from the Diabetic Foot Ulcer Clinic of the
      Endocrinology and Metabolism Research Center of Tehran University of Medical
      Sciences, Tehran, Iran. All patients with a grade 3 ulcer (Wagner Classification)
      with 0.6 <= ankle brachial index <= 1.2, were included. Patients were divided
      into 2 groups; 1 group received ultrasound-assisted wound therapy (UAW) in
      conjunction with standard wound care (n = 20) and the control group received only
      standard wound care. Patients were followed for 6 months. RESULTS: The complete
      healing rate in the study population was 55.7% (control group = 55%, UAW group =
      60%). The mean wound size reduction percentage was significantly higher in the
      UAW group only in the second month (78% +/- 28.7 vs 55.7% +/- 31.4, P = 0.01) and
      third month (63.6% +/- 24.5 vs 39.3% +/- 32.2 , P = 0.02) of follow up, but not
      at 6 months. CONCLUSION: In grade 3 diabetic foot ulcers, LFU debridement
      accompanied by standard wound care can initially accelerate ulcer healing;
      however, there is no significant difference between the 2 modalities in the
      healing rate after 6 months.    .

PMID- 25867039
TI  - Detection of human leukocyte antigen biomarkers in breast cancer utilizing label
      free biosensor technology.
AB  - According to the American Cancer Society, more than 200,000 women will be
      diagnosed with invasive breast cancer each year and approximately 40,000 will die
      from the disease. The human leukocyte antigen (HLA) class I samples peptides
      derived from proteasomal degradation of cellular proteins and presents these
      fragments on the cell surface for interrogation by circulating cytotoxic T
      lymphocytes (CTL). Generation of T-cell receptor mimic (TCRm) monoclonal
      antibodies (mAbs) which recognize breast cancer specific peptide/HLA-A*02:01
      complexes such as those derived from macrophage migration inhibitory factor
      (MIF19-27) and NY-ESO-1157-165 enable detection and destruction of breast cancer
      cells in the absence of an effective anti-tumor CTL response. Intact class I
      HLA/peptide complexes are shed by breast cancer cells and represent potentially
      relevant cancer biomarkers. In this work, a breakthrough biomarker screening
      system for cancer diagnostics incorporating T-cell receptor mimic monoclonal
      antibodies combined with a novel, label-free biosensor utilizing guided-mode
      resonance (GMR) sensor technology is presented. Detection of shed MIF/HLA-A*02:01
      complexes in MDA-MB-231 cell supernatants, spiked human serum, and patient plasma
      is demonstrated. The impact of this work could revolutionize personalized
      medicine through development of companion disease diagnostics for targeted
      immunotherapies. 

PMID- 25867040
TI  - Experience of anaesthesia nurses of perioperative communication in hip fracture
      patients with dementia.
AB  - BACKGROUND: Perioperative care in hip fracture patients with dementia can be
      complex. There is currently little scientific evidence on how care should be
      undertaken. AIMS: The aim of the study was to describe the experience of
      anaesthesia nurses of the difficulties that emerge in care situations and how
      communication with patients can be maintained in the perioperative setting of hip
      fracture surgery. METHODS: Individual interviews were conducted with ten
      anaesthesia nurses (5 men and 5 women). The interviews were carried out at a
      university hospital in Gothenburg (Sweden), and the data were analysed using
      qualitative content analysis. FINDINGS: Three main response categories were
      discerned: 'Communication', 'Dementia as a special issue' and 'Practical issues'.
      Dementia was viewed as one of the most difficult and shifting diseases an
      individual may suffer from. Time must be allocated to communicate clearly and
      patiently, to meticulously plan and carry out care while providing distinct
      information to enable patient participation. Establishing a mental bridgehead by
      confirming the patients' perceptions/feelings significantly reduced distress in a
      majority of the patients. A holistic and respectful approach was deemed mandatory
      at all times. Patients are sometimes dependent on recognition, so that small
      personal items brought close to the patient during surgery can calm the patient.
      State-of-the-art analgesia and anxiolytic medications are mandatory. CONCLUSIONS:
      Perioperative problems can be overcome with patience, empathy and profound
      knowledge of how patients with dementia respond prior to surgery. Our results may
      serve as a source for future care and provide information about hospital settings
      for better perioperative care in patients with dementia.

PMID- 25867041
TI  - Generation of human adipose stem cells through dedifferentiation of mature
      adipocytes in ceiling cultures.
AB  - Mature adipocytes have been shown to reverse their phenotype into fibroblast-like
      cells in vitro through a technique called ceiling culture. Mature adipocytes can
      also be isolated from fresh adipose tissue for depot-specific characterization of
      their function and metabolic properties. Here, we describe a well-established
      protocol to isolate mature adipocytes from adipose tissues using collagenase
      digestion, and subsequent steps to perform ceiling cultures. Briefly, adipose
      tissues are incubated in a Krebs-Ringer-Henseleit buffer containing collagenase
      to disrupt tissue matrix. Floating mature adipocytes are collected on the top
      surface of the buffer. Mature cells are plated in a T25-flask completely filled
      with media and incubated upside down for a week. An alternative 6-well plate
      culture approach allows the characterization of adipocytes undergoing
      dedifferentiation. Adipocyte morphology drastically changes over time of culture.
      Immunofluorescence can be easily performed on slides cultivated in 6-well plates
      as demonstrated by FABP4 immunofluorescence staining. FABP4 protein is present in
      mature adipocytes but down-regulated through dedifferentiation of fat cells.
      Mature adipocyte dedifferentiation may represent a new avenue for cell therapy
      and tissue engineering. 

PMID- 25867043
TI  - Catecholamine Mediates Psychological Stress-Induced Colitis Through a2
      Adrenoreceptor.
AB  - Psychological stress has long been reported to be linked with the disease
      activity of patients with inflammatory bowel disease (IBD). However, the
      mechanisms of psychological stress involved in pathogenesis of IBD are still to
      be elucidated. We have previously shown that catecholamine participates in
      progression of acute colitis through a2-adrenoreceptors. The study aimed to
      explore the pivotal role of catecholamine in psychological stress-induced
      colitis. The expression of dopamine beta-hydroxylase (DBH), the rate-limiting
      enzyme in regulation of catecholamine synthesis, was induced in colon tissues of
      mice with restraint stress, indicating the association of catecholamine synthesis
      with psychological stress. Notably, pretreatment with RX821002, an a2
      adrenoceptor antagonist, attenuated inflammatory responses of psychological
      stress-induced colitis. Intriguingly, DBH levels were elevated in colon tissues
      of patients with active IBD. The study suggests that a2
      adrenoreceptors/catecholamine play pivotal role in psychological stress-induced
      colitis and might contribute to the development of human IBD. 

PMID- 25867042
TI  - High-throughput quantitative real-time RT-PCR assay for determining expression
      profiles of types I and III interferon subtypes.
AB  - Described in this report is a qRT-PCR assay for the analysis of seventeen human
      IFN subtypes in a 384-well plate format that incorporates highly specific locked
      nucleic acid (LNA) and molecular beacon (MB) probes, transcript standards,
      automated multichannel pipetting, and plate drying. Determining expression among
      the type I interferons (IFN), especially the twelve IFN-alpha subtypes, is
      limited by their shared sequence identity; likewise, the sequences of the type
      III IFN, especially IFN-lambda2 and -lambda3, are highly similar. This assay
      provides a reliable, reproducible, and relatively inexpensive means to analyze
      the expression of the seventeen interferon subtype transcripts. 

PMID- 25867044
TI  - The use of ene adducts to study and engineer enoyl-thioester reductases.
AB  - An improved understanding of enzymes' catalytic proficiency and stereoselectivity
      would further enable applications in chemistry, biocatalysis and industrial
      biotechnology. We use a chemical probe to dissect individual catalytic steps of
      enoyl-thioester reductases (Etrs), validating an active site tyrosine as the
      cryptic proton donor and explaining how it had eluded definitive identification.
      This information enabled the rational redesign of Etr, yielding mutants that
      create products with inverted stereochemistry at wild type-like turnover
      frequency. 

PMID- 25867046
TI  - Enhanced genetic analysis of single human bioparticles recovered by simplified
      micromanipulation from forensic 'touch DNA' evidence.
AB  - DNA profiles can be obtained from 'touch DNA' evidence, which comprises
      microscopic traces of human biological material. Current methods for the recovery
      of trace DNA employ cotton swabs or adhesive tape to sample an area of interest.
      However, such a 'blind-swabbing' approach will co-sample cellular material from
      the different individuals, even if the individuals' cells are located in
      geographically distinct locations on the item. Thus, some of the DNA mixtures
      encountered in touch DNA samples are artificially created by the swabbing itself.
      In some instances, a victim's DNA may be found in significant excess thus masking
      any potential perpetrator's DNA. In order to circumvent the challenges with
      standard recovery and analysis methods, we have developed a lower cost, 'smart
      analysis' method that results in enhanced genetic analysis of touch DNA evidence.
      We describe an optimized and efficient micromanipulation recovery strategy for
      the collection of bio-particles present in touch DNA samples, as well as an
      enhanced amplification strategy involving a one-step 5 ul microvolume lysis/STR
      amplification to permit the recovery of STR profiles from the bio-particle
      donor(s). The use of individual or few (i.e., "clumps") bioparticles results in
      the ability to obtain single source profiles. These procedures represent
      alternative enhanced techniques for the isolation and analysis of single
      bioparticles from forensic touch DNA evidence. While not necessary in every
      forensic investigation, the method could be highly beneficial for the recovery of
      a single source perpetrator DNA profile in cases involving physical assault
      (e.g., strangulation) that may not be possible using standard analysis
      techniques. Additionally, the strategies developed here offer an opportunity to
      obtain genetic information at the single cell level from a variety of other non
      forensic trace biological material. 

PMID- 25867047
TI  - Rotational Excitations in CO-CO Collisions at Low Temperature: Time-Independent
      and Multiconfigurational Time-Dependent Hartree Calculations.
AB  - The rotational excitation in collisions between two carbon monoxide molecules was
      studied while combining the use of both time-independent and time-dependent
      formalisms. All of the calculations made use of a recently published four
      dimensional PES for CO dimer. Time-independent scattering calculations were
      performed in the lower part of the collision energy range, thus limiting the
      number of open channels and computational cost. The PES features a low-energy
      path for geared motion that appears to affect the excitation propensities in low
      energy collisions. For reactants colliding without initial rotational excitation,
      symmetric excitations (both monomers excited equally) are strongly favored. This
      behavior deviates significantly from an exponential gap model based on endo- or
      exoergicity. Comparable time-dependent calculations were performed in an extended
      energy range made feasible by the lower cost of those calculations. The wave
      packet propagation in the time-dependent approach was performed with the
      multiconfiguration time-dependent hartree (MCTDH) method and analyses via the
      flux method, and the Tannor and Weeks approach was used to calculate the
      transition probabilities in the energy range up to 1000 cm(-1). We deduce from
      the cross sections the corresponding reaction rates for temperatures between 10
      and 250 K. MCTDH was found to yield well-converged results, where the methods
      overlap, validating the use of MCTDH as an efficient tool to study collision
      processes. 

PMID- 25867045
TI  - Mode of action and pharmacogenomic biomarkers for exceptional responders to
      didemnin B.
AB  - Modern cancer treatment employs many effective chemotherapeutic agents originally
      discovered from natural sources. The cyclic depsipeptide didemnin B has
      demonstrated impressive anticancer activity in preclinical models. Clinical use
      has been approved but is limited by sparse patient responses combined with
      toxicity risk and an unclear mechanism of action. From a broad-scale effort to
      match antineoplastic natural products to their cellular activities, we found that
      didemnin B selectively induces rapid and wholesale apoptosis through dual
      inhibition of PPT1 and EEF1A1. Furthermore, empirical discovery of a small panel
      of exceptional responders to didemnin B allowed the generation of a regularized
      regression model to extract a sparse-feature genetic biomarker capable of
      predicting sensitivity to didemnin B. This may facilitate patient selection in a
      fashion that could enhance and expand the therapeutic application of didemnin B
      against neoplastic disease. 

PMID- 25867048
TI  - [S3 guideline hepatitis C addendum].

PMID- 25867049
TI  - Positive end-expiratory pressure titration at bedside using electrical impedance
      tomography in post-operative cardiac surgery patients.
AB  - BACKGROUND: Post-operative positive end-expiratory pressure (PEEP) setting to
      minimize the risk of ventilator-associated lung injury is still controversial.
      Assessment of regional ventilation distribution by electrical impedance
      tomography (EIT) might be superior as compared with global parameters. The aim of
      this prospective observational study was to compare global dynamic compliance
      (CRS ) with different EIT indices during a short clinical applicable descending
      PEEP trial. METHODS: Twenty mechanically ventilated patients after elective
      cardiac surgery received a standard recruitment manoeuvre (RM) following
      descending PEEP trial in steps of 2 cmH2 O from PEEP 14 cmH2 O to 6 cmH2 O.
      During baseline and all PEEP steps, CRS was assessed and regional ventilation
      distribution was measured by means of EIT. The individual 'best' PEEP values for
      the derived EIT indices and CRS were calculated and compared. RESULTS: The
      descending PEEP trial lasted less than 10 min. CRS increased after the RM and
      showed a maximum value at PEEP 8 cmH2 O. Ventilation distribution shifted more to
      dependent lung regions after RM and back to more non-dependent regions during the
      PEEP trial. Individual 'best' PEEP by CRS showed significantly lower values than
      'best' PEEP by ventilation distribution measured with EIT indices. CONCLUSION:
      During a short descending PEEP trial at bedside, EIT is capable of following the
      status of regional ventilation distribution in ventilated patients. The 'best'
      PEEP value identified by individual maximum CRS was lower than optimal PEEP
      levels as determined by means of EIT indices. EIT could help setting PEEP in post
      operative ventilated patients.

PMID- 25867050
TI  - Influenza virus propagation in embryonated chicken eggs.
AB  - Influenza infection is associated with about 36,000 deaths and more than 200,000
      hospitalizations every year in the United States. The continuous emergence of new
      influenza virus strains due to mutation and re-assortment complicates the control
      of the virus and necessitates the permanent development of novel drugs and
      vaccines. The laboratory-based study of influenza requires a reliable and cost
      effective method for the propagation of the virus. Here, a comprehensive protocol
      is provided for influenza A virus propagation in fertile chicken eggs, which
      consistently yields high titer viral stocks. In brief, serum pathogen-free (SPF)
      fertilized chicken eggs are incubated at 37  degrees C and 55-60% humidity for 10
      11 days. Over this period, embryo development can be easily monitored using an
      egg candler. Virus inoculation is carried out by injection of virus stock into
      the allantoic cavity using a needle. After 2 days of incubation at 37  degrees C,
      the eggs are chilled for at least 4 hr at 4  degrees C. The eggshell above the
      air sac and the chorioallantoic membrane are then carefully opened, and the
      allantoic fluid containing the virus is harvested. The fluid is cleared from
      debris by centrifugation, aliquoted and transferred to -80  degrees C for long
      term storage. The large amount (5-10 ml of virus-containing fluid per egg) and
      high virus titer which is usually achieved with this protocol has made the usage
      of eggs for virus preparation our favorable method, in particular for in vitro
      studies which require large quantities of virus in which high dosages of the same
      virus stock are needed.

PMID- 25867051
TI  - An Efficient Entry to syn- and anti-Selective Isoindolinones via an
      Organocatalytic Direct Mannich/Lactamization Sequence.
AB  - An organocatalytic direct Mannich-lactamization sequence for the syntheses of
      pharmacologically important enantioenriched isoindolinones is reported. The
      method utilizes simple alpha-amino acids to deliver syn- and anti- selective
      isoindolinones with remarkably high enantioselectivity (up to >99% ee) in good to
      excellent yields and diastereomeric ratios. The overall sequence involves one C-C
      and two C-N bond forming events in one pot starting from inexpensive starting
      material. 

PMID- 25867052
TI  - Closed-loop neuro-robotic experiments to test computational properties of
      neuronal networks.
AB  - Information coding in the Central Nervous System (CNS) remains unexplored. There
      is mounting evidence that, even at a very low level, the representation of a
      given stimulus might be dependent on context and history. If this is actually the
      case, bi-directional interactions between the brain (or if need be a reduced
      model of it) and sensory-motor system can shed a light on how encoding and
      decoding of information is performed. Here an experimental system is introduced
      and described in which the activity of a neuronal element (i.e., a network of
      neurons extracted from embryonic mammalian hippocampi) is given context and used
      to control the movement of an artificial agent, while environmental information
      is fed back to the culture as a sequence of electrical stimuli. This architecture
      allows a quick selection of diverse encoding, decoding, and learning algorithms
      to test different hypotheses on the computational properties of neuronal
      networks. 

PMID- 25867053
TI  - Energetics and Solvation Effects at the Photoanode/Catalyst Interface: Ohmic
      Contact versus Schottky Barrier.
AB  - The design of optimal interfaces between photoelectrodes and catalysts is a key
      challenge in building photoelectrochemical cells to split water. Iridium dioxide
      (IrO2) is an efficient catalyst for oxygen evolution, stable in acidic
      conditions, and hence a good candidate to be interfaced with photoanodes. Using
      first-principles quantum mechanical calculations, we investigated the structural
      and electronic properties of tungsten trioxide (WO3) surfaces interfaced with an
      IrO2 thin film. We built a microscopic model of the interface that exhibits a
      formation energy lower than the surface energy of the most stable IrO2 surface,
      in spite of a large lattice mismatch, and has no impurity states pinning the
      Fermi level. We found that, upon full coverage of WO3 by IrO2, the two oxides
      form undesirable Ohmic contacts. However, our calculations predicted that if both
      oxides are partially exposed to water solvent, the relative position of the
      absorber conduction band and the catalyst Fermi level favors charge transfer to
      the catalyst and hence water splitting. We propose that, for oxide
      photoelectrodes interfaced with IrO2, it is advantageous to form rough interfaces
      with the catalyst, e.g., by depositing nanoparticles, instead of sharp interfaces
      with thin films. 

PMID- 25867054
TI  - Risk of malignancy after augmentation cystoplasty: A systematic review.
AB  - OBJECTIVES: To systematically evaluate the evidence regarding the risk of
      malignancy after augmentation cystoplasty. METHOD: A systematic review search was
      performed through Medline and Embase databases using the following key words:
      "cancer," "malignant neoplasm," "cystoplasty," and "bladder augmentation" until
      November 2014. An article was considered relevant to this review if it focused on
      malignant tumors occurring after augmentation cystoplasty performed for benign
      bladder disease. RESULTS: After screening, 57 articles were included in the
      synthesis. The level of evidence was usually poor and results should be
      interpreted with caution. The follow-up time probability to develop a malignant
      tumor(s) after augmentation cystoplasty ranged from 0-5.5% and estimated
      incidence ranged from 0 to 272.3 per 100,000 patients/year. Adenocarcinoma was
      the commonest histological type (51.6%). Malignant lesions predominantly occurred
      at the entero-urinary anastomosis (50%). The mean latency period was 19 years and
      most malignant lesions were diagnosed more than 10 years after surgery (90%).
      Long-term surveillance by cystoscopy is still controversial because of its lack
      of efficiency. Non-invasive techniques have been proposed and need further
      evaluations. Tumors were often diagnosed at an advanced stage within surveillance
      protocols, because of urinary tract related symptoms (64.1%). The carcinogenesis
      pathway is still not clearly understood but several factors are involved.
      CONCLUSION: Augmentation cystoplasty is associated with a risk of malignancy.
      Studies regarding carcinogenesis and surveillance strategies should be considered
      to develop a more efficient follow-up protocol and allow early diagnosis.
      Neurourol. Urodynam. 35:675-682, 2016. (c) 2015 Wiley Periodicals, Inc.

PMID- 25867055
TI  - Amino-ether macrocycle that forms CuII templated threaded heteroleptic complexes:
      a detailed selectivity, structural and theoretical investigations.
AB  - A new oxy(ether)tris(amine) macrocycle, MC has been synthesized for CuII complex
      formation within the cavity of the macrocyclic wheel in endotopic fashion. This
      complex is further reacted with the bidentate chelating ligands, 1,10
      phenanthroline (L1), 2,2'-bipyridyl (L2), 4,4'-dimethyl-2,2'-bipyridyl (L3) and
      5,5'-dimethyl-2,2'-bipyridyl (L4) to achieve the pseudorotaxanes PRT1-PRT4,
      respectively. These bis-heteroleptic complexes were characterized by the
      electrospray ionization mass spectrometry (ESI-MS), UV/Vis, EPR spectroscopy and
      Single-crystal X-ray structural analysis. Binding constants of the heteroleptic
      complexes were found in the range of 1.16 * 10(2) to 1.55 * 103 M(-1) in
      acetonitrile. Further, the double level selectivity studies of MC using different
      metal ions [CoII, NiII, CuII, ZnII] and a number of simple bidentate chelating
      ligands shows the selective formation of PRT1 that justifies the self-sorting
      nature of the system. Further, substitution of axles from pseudorotaxanes PRT2
      PRT4 could also be achieved by L1 with nearly 100% efficiency. To corroborate the
      experimental studies (comparison with the crystal geometry, importance of the pi
      pi stacking, etc.) the geometries of the pseudorotaxanes were optimized using DFT
      (B3LYP) in the gas phase.

PMID- 25867056
TI  - Face recognition in newly hatched chicks at the onset of vision.
AB  - How does face recognition emerge in the newborn brain? To address this question,
      we used an automated controlled-rearing method with a newborn animal model: the
      domestic chick (Gallus gallus). This automated method allowed us to examine
      chicks' face recognition abilities at the onset of both face experience and
      object experience. In the first week of life, newly hatched chicks were raised in
      controlled-rearing chambers that contained no objects other than a single virtual
      human face. In the second week of life, we used an automated forced-choice
      testing procedure to examine whether chicks could distinguish that familiar face
      from a variety of unfamiliar faces. Chicks successfully distinguished the
      familiar face from most of the unfamiliar faces-for example, chicks were
      sensitive to changes in the face's age, gender, and orientation (upright vs.
      inverted). Thus, chicks can build an accurate representation of the first face
      they see in their life. These results show that the initial state of face
      recognition is surprisingly powerful: Newborn visual systems can begin encoding
      and recognizing faces at the onset of vision.

PMID- 25867057
TI  - A multi-detection assay for malaria transmitting mosquitoes.
AB  - The Anopheles gambiae species complex includes the major malaria transmitting
      mosquitoes in Africa. Because these species are of such medical importance,
      several traits are typically characterized using molecular assays to aid in
      epidemiological studies. These traits include species identification, insecticide
      resistance, parasite infection status, and host preference. Since populations of
      the Anopheles gambiae complex are morphologically indistinguishable, a polymerase
      chain reaction (PCR) is traditionally used to identify species. Once the species
      is known, several downstream assays are routinely performed to elucidate further
      characteristics. For instance, mutations known as KDR in a para gene confer
      resistance against DDT and pyrethroid insecticides. Additionally, enzyme-linked
      immunosorbent assays (ELISAs) or Plasmodium parasite DNA detection PCR assays are
      used to detect parasites present in mosquito tissues. Lastly, a combination of
      PCR and restriction enzyme digests can be used to elucidate host preference
      (e.g., human vs. animal blood) by screening the mosquito bloodmeal for host
      specific DNA. We have developed a multi-detection assay (MDA) that combines all
      of the aforementioned assays into a single multiplex reaction genotyping 33SNPs
      for 96 or 384 samples at a time. Because the MDA includes multiple markers for
      species, Plasmodium detection, and host blood identification, the likelihood of
      generating false positives or negatives is greatly reduced from previous assays
      that include only one marker per trait. This robust and simple assay can detect
      these key mosquito traits cost-effectively and in a fraction of the time of
      existing assays. 

PMID- 25867058
TI  - High levels of DJ-1 protein and isoelectric point 6.3 isoform in sera of breast
      cancer patients.
AB  - In patients with cancer and Parkinson's disease, the DJ-1 protein may be secreted
      into the serum during the impaired response of the underlying cell-protective
      mechanisms. In order to determine the clinical significance of DJ-1 protein in
      the sera of breast cancer patients, we examined blood samples from a breast
      cancer group (n = 180) and a non-cancerous control group (n = 300). Higher levels
      of DJ-1 were detected in the breast cancer group (mean level, 42.7 ng/mL) than
      the control group (28.3 ng/mL) by ELISA (P = 0.019). Higher DJ-1 levels were
      significantly associated with advanced clinical grade, according to the TNM
      classification, negative hormone receptor status, and high Ki-67 labeling index,
      of biopsied materials; samples showed low DJ-1 protein expression despite
      upregulated DJ-1 mRNA. DJ-1 isoforms could be detected clearly in 17 blood
      samples (from 11 breast cancer patients, and 6 non-cancerous controls) by 2-D gel
      electrophoresis and immunoblot analysis. The isoform at the pI of 6.3 showed the
      highest intensity in all 11 cancer cases. Conversely, in the 6 non-cancerous
      cases, isoforms other than the pI 6.3 isoform were highly expressed, and there
      was a significant difference in the isoform pattern between breast cancer cases
      and controls (P = 0.00025). These data indicate that high levels of DJ-1,
      probably of isoform at pI 6.3, is a candidate serum marker of breast cancer. 

PMID- 25867059
TI  - Effect of chemical environment on the dynamics of water confined in calcium
      silicate minerals: natural and synthetic tobermorite.
AB  - Confined water in the slit mesopores of the mineral tobermorite provides an
      excellent model system for analyzing the dynamic properties of water confined in
      cement-like materials. In this work, we use broadband dielectric spectroscopy
      (BDS) to analyze the dynamic of water entrapped in this crystalline material. Two
      samples, one natural and one synthetic, were analyzed, and despite their similar
      structure, the motion of confined water in their zeolitic cavity displays
      considerably different behavior. The water dynamics splits into two different
      behaviors depending on the chemical nature of the otherwise identical structural
      environment: water molecules located in areas where the primary building units
      are SiO4 relax slowly compared to water molecules located in cavities built with
      both AlO4 and SiO4. Compared to water confined in regular porous systems, water
      restricted in tobermorite is slower, indicating that the mesopore structure
      induces high disorder in the water structure. A comparison with water confined in
      the C-S-H gel is also discussed in this work. The strong dynamical changes in
      water due to the presence of aluminum might have important implications in the
      chemical transport of ions within hydrated calcium silicates, a process that
      governs the leaching and chemical degradation of cement. 

PMID- 25867060
TI  - Role of Runx2 phosphorylation in prostate cancer and association with metastatic
      disease.
AB  - The osteogenic transcription factor, Runx2, is abnormally expressed in prostate
      cancer (PCa) and associated with metastatic disease. During bone development,
      Runx2 is activated by signals known to be hyperactive in PCa including the
      RAS/MAP kinase pathway, which phosphorylates Runx2 on multiple serine residues
      including S301 and S319 (equivalent to S294 and S312 in human Runx2). This study
      examines the role of these phosphorylation sites in PCa. Runx2 was preferentially
      expressed in more invasive PCa cell lines (PC3>C4-2B>LNCaP). Furthermore,
      analysis using a P-S319-Runx2-specific antibody revealed that the ratio of P-S319
      Runx2/total Runx2 as well as P-ERK/total ERK was highest in PC3 followed by C4-2B
      and LNCaP cells. These results were confirmed by immunofluorescence confocal
      microscopy, which showed a higher percentage of PC3 cells staining positive for P
      S319-Runx2 relative to C4-2B and LNCaP cells. Phosphorylated Runx2 had an
      exclusively nuclear localization. When expressed in prostate cell lines, wild
      type Runx2 increased metastasis-associated gene expression, in vitro migratory
      and invasive activity as well as in vivo growth of tumor cell xenografts. In
      contrast, S301A/S319A phosphorylation site mutations greatly attenuated these
      Runx2 responses. Analysis of tissue microarrays from 129 patients revealed strong
      nuclear staining with the P-S319-Runx2 antibody in primary PCas and metastases. P
      S319-Runx2 staining was positively correlated with Gleason score and occurrence
      of lymph node metastases while little or no Runx2 phosphorylation was seen in
      normal prostate, benign prostate hyperplasia or prostatitis indicating that Runx2
      S319 phosphorylation is closely associated with PCa induction and progression
      towards an aggressive phenotype. These studies establish the importance of Runx2
      phosphorylation in prostate tumor growth and highlight its value as a potential
      diagnostic marker and therapeutic target. 

PMID- 25867061
TI  - MiRNA-621 sensitizes breast cancer to chemotherapy by suppressing FBXO11 and
      enhancing p53 activity.
AB  - MicroRNAs (miRNAs) have been demonstrated to have critical roles in regulating
      cancer cell proliferation, survival and sensitivity to chemotherapy. The
      potential application of using miRNAs to predict therapeutic response to cancer
      treatment holds high promise, but miRNAs with predictive value remain to be
      identified and underlying mechanisms have not been completely understood. Here,
      we show a strong correlation between miR-621 expression and chemosensitivity to
      paclitaxel plus carboplatin (PTX/CBP) regimen, an effective neoadjuvant
      chemotherapy for breast cancer patients. High level of miR-621 predicts better
      response to PTX/CBP regimen neoadjuvant chemotherapy in breast cancer patients,
      who also tend to achieve pathological complete response. Ectopic overexpression
      of miR-621 promoted apoptosis and increased chemosensitivity to PTX and CBP both
      in cultured breast cancer cells and in xenograft tumor model. We further show
      that FBXO11 is a direct functional target of miR-621 and miR-621 level is
      negatively correlated with FBXO11 expression in breast cancer patients. Ectopic
      expression of FBXO11 attenuated increased apoptosis in breast cancer cells
      overexpressing miR-621 upon PTX or CBP treatment. Consistently, high FBXO11
      expression significantly correlated with poor survival in breast cancer patients.
      Mechanistically, we found in breast cancer cells FBXO11 interacts with p53 and
      promotes its neddylation, which suppressed the p53 transactivity. Accordingly,
      miR-621-dependent FBXO11 suppression enhanced p53 activity and increased
      apoptosis in breast cancer cells exposed to chemotherapeutics. Taken together,
      our data suggest that miR-621 enhances chemosensitivity of breast cancer cells to
      PTX/CBP chemotherapy by suppressing FBXO11-dependent inhibition of p53. miR-621
      may serve as a predictive biomarker and a potential therapeutic target in breast
      cancer treatment.

PMID- 25867062
TI  - Anti-androgen flutamide suppresses hepatocellular carcinoma cell proliferation
      via the aryl hydrocarbon receptor mediated induction of transforming growth
      factor-beta1.
AB  - The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor
      and a member of the basic helix-loop-helix PER/ARNT/SIM family of chemosensors
      and developmental regulators. The AhR is widely known as a mediator of dioxin
      toxicity; however, it also suppresses cancer cell proliferation and recent
      findings have implicated its role as a tumor suppressor. We conducted a chemical
      library screen to identify nontoxic AhR ligands with anti-cancer effects and
      discovered flutamide (Eulexin) as a putative AhR ligand. Flutamide is an androgen
      receptor (AR) antagonist approved by the United States Food and Drug
      Administration for the treatment of prostate cancer. We found that flutamide
      inhibited the growth of several cancer cell lines independent of AR status, and
      that suppression of AhR expression reversed the anti-proliferative effects of
      flutamide. We investigated the AhR-dependent mechanism of action of flutamide in
      human hepatocellular carcinoma cells and identified that transforming growth
      factor-beta1 (TGF-beta1) is induced by flutamide in an AhR-dependent manner. In
      contrast, the potent AhR agonist 2,3,7,8-Tetrachlorodibenzo-p-dioxin had no
      effect on TGF-beta1 expression, indicating the ligand specificity of AhR
      activation. We also determined that TGF-beta1 induction is required for the AhR
      dependent growth inhibitory effects of flutamide. Therefore, flutamide may be
      effective in AhR-positive cancers that are sensitive to TGF-beta1 signaling, such
      as hepatocellular carcinoma. 

PMID- 25867063
TI  - SUMO modification of Akt regulates global SUMOylation and substrate SUMOylation
      specificity through Akt phosphorylation of Ubc9 and SUMO1.
AB  - SUMOylation is an important post-translational modification, and Akt SUMOylation
      was found to regulate cell proliferation, tumorigenesis and cell cycle, but the
      molecular mechanism of Akt SUMOylation is less well known. Here, we show both
      endogenous and ectopic Akt SUMOylation and Lys276 is the major SUMO acceptor on
      Akt. Further, Akt SUMOylation is Akt phosphorylation dependent and Akt
      SUMOylation increases Akt kinase activity without affecting the phosphorylation
      level of Akt. Moreover, endogenous Akt SUMOylation is enhanced by insulin
      treatment and this is Akt activity dependent. Heat-shock stimulus also increases
      Akt SUMOylation and it is also Akt activity dependent. Endogenous Akt SUMOylation
      is also found in the rat brain and it is enhanced by insulin-like growth factor-1
      stimulation. In addition, Akt directly phosphorylates Ubc9 at Thr35 and
      phosphorylates SUMO1 at Thr76. Ubc9 phosphorylation at Thr35 promotes Ubc9
      thioester bond formation and SUMO1 phosphorylation at Thr76 stabilizes the SUMO1
      protein. Through these distinct mechanisms, Akt SUMOylation regulates global
      SUMOylation, including Akt and Ubc9 SUMOylation, and substrate SUMOylation
      specificity, including STAT1 and CREB SUMOylation, in different manners. Akt
      SUMOylation also enhances phosphatase and tensin homolog (PTEN) SUMOylation
      through Akt phosphorylation of Ubc9 and SUMO1, which serves as an endogenous
      mechanism to stop the positive feedback loop resulted from Akt activation.
      Further, Akt SUMOylation increases cyclin D1 expression and cell proliferation,
      and these effects are also mediated through Ubc9 phosphorylation at Thr35 and
      SUMO1 phosphorylation at Thr76. Here, we have identified a novel mechanism for
      SUMOylation regulation. Because of the important role Akt plays in tumorigenesis,
      this mechanism may also be involved in Akt-regulated tumorigenesis. 

PMID- 25867064
TI  - miR-186 regulation of Twist1 and ovarian cancer sensitivity to cisplatin.
AB  - Epithelial-mesenchymal transition (EMT) has an established role in promoting
      tumor progression and the acquisition of therapeutic resistance. Here, the EMT
      phenotype was detected in cisplatin-resistant ovarian cancer tissues and cell
      lines, and correlated with decreased miR-186 expression, increased Twist1
      expression, chemoresistance and poor prognosis in epithelial ovarian cancer (EOC)
      patients. Introducing miR-186 into EOC cells led to a reduction in twist family
      bHLH transcription factor 1 (Twist1) expression along with morphological,
      functional and molecular changes consistent with mesenchymal-to-epithelial
      transition, G1 cell-cycle arrest and enhanced cell apoptosis, which consequently
      rendered the cells more sensitive to cisplatin in vitro and in vivo. Furthermore,
      luciferase reporter and rescue assay results showed that the EMT and drug
      resistance reversal in response to miR-186 was mediated by Twist1. Collectively,
      these findings implicate miR-186 as an attractive candidate for overcoming
      chemoresistance in ovarian cancer therapy. 

PMID- 25867065
TI  - Inhibition of B-Raf/MEK/ERK signaling suppresses DR5 expression and impairs
      response of cancer cells to DR5-mediated apoptosis and T cell-induced killing.
AB  - Inhibition of B-Raf/MEK/ERK signaling is an effective therapeutic strategy
      against certain types of cancers such as melanoma and thyroid cancer. While
      demonstrated to be effective anticancer agents, B-Raf or MEK inhibitors have also
      been associated with early tumor progression and development of secondary
      neoplasms. The ligation of tumor necrosis factor-related apoptosis-inducing
      ligand (TRAIL) with its receptor, death receptor 5 (DR5), leading to induction of
      apoptosis, offers a promising anticancer strategy. Importantly, this is also a
      natural immunosurveillance mechanism against cancer development. We previously
      demonstrated that activated B-Raf/MEK/ERK signaling positively regulates DR5
      expression. Hence, our current work sought to address whether B-Raf/MEK/ERK
      inhibition and the consequent suppression of DR5 expression impede cancer cell
      response to DR5 activation-induced apoptosis and activated immune cell-induced
      killing. We found that both B-Raf (for example, PLX4032) and MEK inhibitors (for
      example, AZD6244 and PD0325901) effectively inhibited ERK1/2 phosphorylation and
      reduced DR5 levels in both human thyroid cancer and melanoma cells. Similar to
      the observed effect of genetic knockdown of the B-Raf gene, pre-treatment of
      cancer cell lines with either B-Raf or MEK inhibitors attenuated or abolished
      cellular apoptotic response induced by TRAIL or the DR5 agonistic antibody AMG655
      or cell killing by activated T cells. Our findings clearly show that inhibition
      of B-Raf/MEK/ERK signaling suppresses DR5 expression and impairs DR5 activation
      induced apoptosis and T cell-mediated killing of cancer cells. These findings
      suggest a potential negative impact of B-Raf or MEK inhibition on TRAIL- or DR5
      mediated anticancer therapy and on TRAIL/DR5-mediated immune-clearance of cancer
      cells. 

PMID- 25867066
TI  - Reactive oxygen species regulate Smac mimetic/TNFalpha-induced necroptotic
      signaling and cell death.
AB  - Necroptosis represents a key programmed cell death pathway involved in various
      physiological and pathophysiological conditions. However, the role of reactive
      oxygen species (ROS) in necroptotic signaling has remained unclear. In the
      present study, we identify ROS as critical regulators of BV6/tumor necrosis
      factor-alpha (TNFalpha)-induced necroptotic signaling and cell death. We show
      that BV6/TNFalpha-induced cell death depends on ROS production, as several ROS
      scavengers such as butylated hydroxyanisole, N-acetylcysteine, alpha-tocopherol
      and ethyl pyruvate significantly rescue cell death. Before cell death,
      BV6/TNFalpha-stimulated ROS generation promotes stabilization of the receptor
      interacting protein kinase 1 (RIP1)/RIP3 necrosome complex via a potential
      positive feedback loop, as on the one hand radical scavengers attenuate RIP1/RIP3
      necrosome assembly and phosphorylation of mixed lineage kinase domain like
      (MLKL), but on the other hand silencing of RIP1 or RIP3 reduces ROS production.
      Although MLKL knockdown effectively decreases BV6/TNFalpha-induced cell death, it
      does not affect RIP1/RIP3 interaction and only partly reduces ROS generation.
      Moreover, the deubiquitinase cylindromatosis (CYLD) promotes BV6/TNFalpha-induced
      ROS generation and necrosome assembly even in the presence of BV6, as CYLD
      silencing attenuates these events. Genetic silencing of phosphoglycerate mutase 5
      or dynamin-related protein 1 (Drp1) fails to protect against BV6/TNFalpha-induced
      cell death. By demonstrating that ROS are involved in regulating BV6/TNFalpha
      induced necroptotic signaling, our study provides new insights into redox
      regulation of necroptosis. 

PMID- 25867067
TI  - Activation of mechanosensitive ion channel TRPV4 normalizes tumor vasculature and
      improves cancer therapy.
AB  - Tumor vessels are characterized by abnormal morphology and hyperpermeability that
      together cause inefficient delivery of chemotherapeutic agents. Although vascular
      endothelial growth factor has been established as a critical regulator of tumor
      angiogenesis, the role of mechanical signaling in the regulation of tumor
      vasculature or tumor endothelial cell (TEC) function is not known. Here we show
      that the mechanosensitive ion channel transient receptor potential vanilloid 4
      (TRPV4) regulates tumor angiogenesis and tumor vessel maturation via modulation
      of TEC mechanosensitivity. We found that TECs exhibit reduced TRPV4 expression
      and function, which is correlated with aberrant mechanosensitivity towards
      extracellular matrix stiffness, increased migration and abnormal angiogenesis by
      TEC. Further, syngeneic tumor experiments revealed that the absence of TRPV4
      induced increased vascular density, vessel diameter and reduced pericyte coverage
      resulting in enhanced tumor growth in TRPV4 knockout mice. Importantly,
      overexpression or pharmacological activation of TRPV4 restored aberrant TEC
      mechanosensitivity, migration and normalized abnormal angiogenesis in vitro by
      modulating Rho activity. Finally, a small molecule activator of TRPV4,
      GSK1016790A, in combination with anticancer drug cisplatin, significantly reduced
      tumor growth in wild-type mice by inducing vessel maturation. Our findings
      demonstrate TRPV4 channels to be critical regulators of tumor angiogenesis and
      represent a novel target for anti-angiogenic and vascular normalization
      therapies. 

PMID- 25867068
TI  - Fer tyrosine kinase oligomer mediates and amplifies Src-induced tumor
      progression.
AB  - c-Src is upregulated in various human cancers, suggesting its role in malignant
      progression. However, the molecular circuits of c-Src oncogenic signaling remain
      elusive. Here we show that Fer tyrosine kinase oligomer mediates and amplifies
      Src-induced tumor progression. Previously, we showed that transformation of
      fibroblasts is promoted by the relocation of c-Src to non-raft membranes. In this
      study, we identified Fer and ezrin as non-raft c-Src targets. c-Src directly
      activated Fer by initiating its autophosphorylation, which was further amplified
      by Fer oligomerization. Fer interacted with active c-Src at focal adhesion
      membranes and activated Fer-phosphorylated ezrin to induce cell transformation.
      Fer was also crucial for cell transformation induced by v-Src or epidermal growth
      factor receptor activation. Furthermore, Fer activation was required for
      tumorigenesis and invasiveness in some cancer cells in which c-Src is
      upregulated. We propose that the Src-Fer axis represents a new therapeutic target
      for treatment of a subset of human cancers. 

PMID- 25867070
TI  - Hyperthermic intraperitoneal chemotherapy leads to an anticancer immune response
      via exposure of cell surface heat shock protein 90.
AB  - The occurrence of peritoneal carcinomatosis is a major cause of treatment failure
      in colorectal cancer and is considered incurable. However, new therapeutic
      approaches have been proposed, including cytoreductive surgery combined with
      hyperthermic intraperitoneal chemotherapy (HIPEC). Although HIPEC has been
      effective in selected patients, it is not known how HIPEC prolongs a patient's
      lifespan. Here, we have demonstrated that HIPEC-treated tumor cells induce the
      activation of tumor-specific T cells and lead to vaccination against tumor cells
      in mice. We have established that this effect results from the HIPEC-mediated
      exposure of heat shock protein (HSP) 90 at the plasma membrane. Inhibition or
      blocking of HSP90, but not HSP70, prevented the HIPEC-mediated antitumoral
      vaccination. Our work raises the possibility that the HIPEC procedure not only
      kills tumor cells but also induces an efficient anticancer immune response,
      therefore opening new opportunities for cancer treatment. 

PMID- 25867069
TI  - The NEDD8 inhibitor MLN4924 increases the size of the nucleolus and activates p53
      through the ribosomal-Mdm2 pathway.
AB  - The ubiquitin-like molecule NEDD8 is essential for viability, growth and
      development, and is a potential target for therapeutic intervention. We found
      that the small molecule inhibitor of NEDDylation, MLN4924, alters the morphology
      and increases the surface size of the nucleolus in human and germline cells of
      Caenorhabditis elegans in the absence of nucleolar fragmentation. SILAC
      proteomics and monitoring of rRNA production, processing and ribosome profiling
      shows that MLN4924 changes the composition of the nucleolar proteome but does not
      inhibit RNA Pol I transcription. Further analysis demonstrates that MLN4924
      activates the p53 tumour suppressor through the RPL11/RPL5-Mdm2 pathway, with
      characteristics of nucleolar stress. The study identifies the nucleolus as a
      target of inhibitors of NEDDylation and provides a mechanism for p53 activation
      upon NEDD8 inhibition. It also indicates that targeting the nucleolar proteome
      without affecting nucleolar transcription initiates the required signalling
      events for the control of cell cycle regulators. 

PMID- 25867071
TI  - Negative regulation of the p300-p53 interplay by DDX24.
AB  - Numerous studies indicate that p300 acts as a key transcriptional cofactor in
      vivo, at least, in part, by modulating activities of p53 by acetylation.
      Nevertheless, the regulation of the p53-p300 interplay is not completely
      understood. Here, we have identified the DEAD (Asp-Glu-Ala-Asp) box RNA helicase
      24 (DDX24) as a novel regulator of the p300-p53 axis. We found that DDX24
      interacts with p300, and this interaction leads to suppression of p300-mediated
      acetylation of p53. Notably, RNA interference-mediated knockdown of endogenous
      DDX24 significantly increases the acetylation levels of endogenous p53 in human
      cancer cells and subsequently promotes p53-mediated activation of its
      transcriptional targets such as p21 and p53 upregulated modulator of apoptosis
      (PUMA). In contrast, DDX24 expression inhibits the p300-p53 interaction and
      suppresses p300-mediated acetylation of p53. Moreover, DDX24 is overexpressed in
      human cancer cells and reduction of DDX24 protein levels by RNA interference
      induces cell cycle arrest and senescence in a p53-dependent manner. These results
      reveal DDX24 as an important regulator of p300 and suggest that the modulation of
      the p53-p300 interplay by DDX24 is critical in controlling p53 activities in
      human cancer cells. 

PMID- 25867072
TI  - mTOR inhibitors induce apoptosis in colon cancer cells via CHOP-dependent DR5
      induction on 4E-BP1 dephosphorylation.
AB  - The mammalian target of rapamycin (mTOR) is commonly activated in colon cancer.
      mTOR complex 1 (mTORC1) is a major downstream target of the PI3K/ATK pathway and
      activates protein synthesis by phosphorylating key regulators of messenger RNA
      translation and ribosome synthesis. Rapamycin analogs Everolimus and Temsirolimus
      are non-ATP-competitive mTORC1 inhibitors, and suppress proliferation and tumor
      angiogenesis and invasion. We now show that apoptosis plays a key role in their
      anti-tumor activities in colon cancer cells and xenografts through the DR5, FADD
      and caspase-8 axis, and is strongly enhanced by tumor necrosis factor-related
      apoptosis-inducing ligand (TRAIL) and 5-fluorouracil. The induction of DR5 by
      rapalogs is mediated by the ER stress regulator and transcription factor CHOP,
      but not the tumor suppressor p53, on rapid and sustained inhibition of 4E-BP1
      phosphorylation, and attenuated by eIF4E expression. ATP-competitive mTOR/PI3K
      inhibitors also promote DR5 induction and FADD-dependent apoptosis in colon
      cancer cells. These results establish activation of ER stress and the death
      receptor pathway as a novel anticancer mechanism of mTOR inhibitors. 

PMID- 25867074
TI  - Structural properties of the water/membrane interface of a bilayer built of the
      E. coli lipid A.
AB  - Lipid A is the most chemically invariant part of lipopolysaccharides (LPS). Both
      lipid A and LPS constitute the external layer of the outer membrane of Gram
      negative bacteria. E. coli-specific hexacyl lipid A (ECLA) forms stable bilayers
      in the presence of sodium or magnesium cations. To characterize biologically
      relevant properties of the ECLA bilayer, and in particular its water/membrane
      interface, 800 ns molecular dynamics (MD) simulations of fully hydrated bilayers
      made of ECLA at 50  degrees C (i.e., 6  degrees C above the main phase
      transition) were performed. The validation of the computer model for the ECLA
      bilayer was performed using available experimental data. The overall good
      agreement with the data was found. An ECLA molecule makes on average ~1.3 ion
      mediated bridges with neighboring lipid molecules. The average number of
      interlipid hydrogen bonds is 2.7. The abundance of such intermolecular links
      results in tight packing of ECLA molecules in the bilayer and explains the
      relatively small value of the surface area per lipid (1.515 nm(2)). 

PMID- 25867073
TI  - MicroRNAs as mediators and communicators between cancer cells and the tumor
      microenvironment.
AB  - Cancer cells grow in an environment comprised of multiple components that support
      tumor growth and contribute to therapy resistance. Major cell types in the tumor
      microenvironment are fibroblasts, endothelial cells and infiltrating immune cells
      all of which communicate with cancer cells. One way that these cell types promote
      cancer progression is by altering the expression of microRNAs (miRNAs), small
      noncoding RNAs that negatively regulate protein expression, either in the cancer
      cells or in the associated normal cells. Changes in miRNA expression can be
      brought about by direct interaction between the stromal cells and cancer cells,
      by paracrine factors secreted by any of the cell types or even through direct
      communication between cells through secreted miRNAs. Understanding the role of
      miRNAs in the complex interactions between the tumor and cells in its
      microenvironment is necessary if we are to understand tumor progression and
      devise new treatments. 

PMID- 25867075
TI  - Do Patients of Subspecialist Physicians Benefit from Written Asthma Action Plans?
AB  - RATIONALE: Asthma clinical guidelines suggest written asthma action plans are
      essential for improving self-management and outcomes. OBJECTIVES: To assess the
      efficacy of written instructions in the form of a written asthma action plan
      provided by subspecialist physicians as part of usual asthma care during office
      visits. METHODS: A total of 407 children and adults with persistent asthma
      receiving first-time care in pulmonary and allergy practices at 4 urban medical
      centers were randomized to receive either written instructions (n = 204) or no
      written instructions other than prescriptions (n = 203) from physicians.
      MEASUREMENTS AND MAIN RESULTS: Using written asthma action plan forms as a
      vehicle for providing self-management instructions did not have a significant
      effect on any of the primary outcomes: (1) asthma symptom frequency, (2)
      emergency visits, or (3) asthma quality of life from baseline to 12-month follow
      up. Both groups showed similar and significant reductions in asthma symptom
      frequency (daytime symptoms [P < 0.0001], nocturnal symptoms [P < 0.0001], beta
      agonist use [P < 0.0001]). There was also a significant reduction in emergency
      visits for the intervention (P < 0.0001) and control (P < 0.0006) groups. There
      was significant improvement in asthma quality-of-life scores for adults (P <
      0.0001) and pediatric caregivers (P < 0.0001). CONCLUSIONS: Our results suggest
      that using a written asthma action plan form as a vehicle for providing asthma
      management instructions to patients with persistent asthma who are receiving
      subspecialty care for the first time confers no added benefit beyond subspecialty
      based medical care and education for asthma. Clinical trial registered with
      www.clinicaltrials.gov (NCT 00149461).

PMID- 25867076
TI  - Anti-hypertensive and renoprotective effects of berberine in spontaneously
      hypertensive rats.
AB  - OBJECTIVES: We aimed to investigate the effects of berberine on renin-angiotensin
      system (RAS) and pro-inflammatory cytokines, as well as its effects on blood
      pressure and renal damage in spontaneously hypertensive rats. METHODS: Berberine
      was administrated to spontaneously hypertensive rats (SHR rats) between 3 and 20
      weeks of age. Blood pressure was monitored in 3-, 6-, 9-, 12-, 16- and 20-week
      old SHR rats and age-matched Wistar Kyoto rats (WKY rats). Besides, we measured
      levels of angiotensin II, aldosterone and pre-inflammatory cytokines (IL-6, IL
      17, IL-23) in serum and kidney, as well as levels of collagen III and collagen IV
      in kidney and urinary markers of renal injury (osteopontin, kidney-injury
      molecule (KIM-1) and albumin) in 3-, 6-, 9-, 12-, 16- and 20-week-old SHR rats
      and WKY rats. Glomerulosclerosis was also assessed with hematoxylin and eosin
      staining. RESULTS: SHR rats developed hypertension at the age of 6 weeks and had
      increased levels of angiotensin II, aldosterone, IL-6, IL-17, IL-23, collagen
      III, collagen IV, osteopontin, KIM-1 and albumin, as well as more severe
      glomerulosclerosis, compared to the aged-matched WKY rats. Berberine delayed the
      onset and attenuated the severity of hypertension, as well as partially inhibited
      the increases of the above substances in SHR rats. CONCLUSION: Berberine could
      delay the onset and attenuate the severity of hypertension, as well as ameliorate
      hypertension-induced renal damage in SHR rats. Furthermore, berberine could
      inhibit the activities of RAS and pre-inflammatory cytokines IL-6, IL-17 and IL
      23, which are involved in the pathophysiology of hypertension.

PMID- 25867078
TI  - Does the Transcription Factor NemR Use a Regulatory Sulfenamide Bond to Sense
      Bleach?
AB  - Reactive chlorine species (RCS), such as hypochlorous acid (i.e., bleach), are
      antimicrobial oxidants produced by the innate immune system. Like many redox
      regulated transcription factors, the Escherichia coli repressor NemR responds to
      RCS by using the reversible oxidation of highly conserved cysteines to alter its
      DNA-binding affinity. However, earlier work showed that RCS response in NemR does
      not depend on any commonly known oxidative cysteine modifications. We have now
      determined the crystal structure of NemR, showing that the regulatory cysteine,
      Cys106, is in close proximity to a highly conserved lysine (Lys175). We used
      crystallographic, biochemical, and mass spectrometric analyses to analyze the
      role of this lysine residue in RCS sensing. Based on our results, we hypothesize
      that RCS treatment of NemR results in the formation of a reversible Cys106-Lys175
      sulfenamide bond. This is, to our knowledge, the first description of a protein
      whose function is regulated by a cysteine-lysine sulfenamide thiol switch,
      constituting a novel addition to the biological repertoire of functional redox
      switches.

PMID- 25867077
TI  - Analytical tools for the analysis of beta-carotene and its degradation products.
AB  - beta-Carotene, the precursor of vitamin A, possesses pronounced radical
      scavenging properties. This has centered the attention on beta-carotene dietary
      supplementation in healthcare as well as in the therapy of degenerative disorders
      and several cancer types. However, two intervention trials with beta-carotene
      have revealed adverse effects on two proband groups, that is, cigarette smokers
      and asbestos-exposed workers. Beside other causative reasons, the detrimental
      effects observed have been related to the oxidation products of beta-carotene.
      Their generation originates in the polyene structure of beta-carotene that is
      beneficial for radical scavenging, but is also prone to oxidation. Depending on
      the dominant degradation mechanism, bond cleavage might occur either randomly or
      at defined positions of the conjugated electron system, resulting in a diversity
      of cleavage products (CPs). Due to their instability and hydrophobicity, the
      handling of standards and real samples containing beta-carotene and related CPs
      requires preventive measures during specimen preparation, analyte extraction, and
      final analysis, to avoid artificial degradation and to preserve the initial
      analyte portfolio. This review critically discusses different preparation
      strategies of standards and treatment solutions, and also addresses their
      protection from oxidation. Additionally, in vitro oxidation strategies for the
      generation of oxidative model compounds are surveyed. Extraction methods are
      discussed for volatile and non-volatile CPs individually. Gas chromatography
      (GC), (ultra)high performance liquid chromatography (U)HPLC, and capillary
      electrochromatography (CEC) are reviewed as analytical tools for final analyte
      analysis. For identity confirmation of analytes, mass spectrometry (MS) is
      indispensable, and the appropriate ionization principles are comprehensively
      discussed. The final sections cover analysis of real samples and aspects of
      quality assurance, namely matrix effects and method validation. 

PMID- 25867079
TI  - Identification of the avian RBP7 gene as a new adipose-specific gene and RBP7
      promoter-driven GFP expression in adipose tissue of transgenic quail.
AB  - The discovery of an increasing number of new adipose-specific genes has
      significantly contributed to our understanding of adipose tissue biology and the
      etiology of obesity and its related diseases. In the present study, comparison of
      gene expression profiles among various tissues was performed by analysis of
      chicken microarray data, leading to identification of RBP7 as a novel adipose
      specific gene in chicken. Adipose-specific expression of RBP7 in the avian
      species was further confirmed at the protein and mRNA levels. Examination of the
      transcription factor binding sites within the chicken RBP7 promoter by
      Matinspector software revealed potential binding sites for adipogenic
      transcription factors. This led to the hypothesis that the RBP7 promoter can be
      utilized to overexpress a transgene in adipose tissue in order to further
      investigate the function of a transgene in adipose tissue. Several lines of
      transgenic quail containing a green fluorescent protein (GFP) gene under the
      control of the RBP7 promoter were generated using lentivirus-mediated gene
      transfer. The GFP expression in transgenic quail was specific to adipose tissue
      and increased after adipocyte differentiation. This expression pattern was
      consistent with endogenous RBP7 expression, suggesting the RBP7 promoter is
      sufficient to overexpress a gene of interest in adipose tissue at later
      developmental stages. These findings will lead to the establishment of a novel
      RBP7 promoter cassette which can be utilized for overexpressing genes of interest
      in adipose tissue in vivo to study the function of genes in adipose tissue
      development and lipid metabolism. 

PMID- 25867080
TI  - Molecular Basis for Fe(III)-Independent Curcumin Potentiation of Cystic Fibrosis
      Transmembrane Conductance Regulator Activity.
AB  - Curcumin potentiates the phosphorylation-dependent activity of human cystic
      fibrosis transmembrane conductance regulator (CFTR) in Fe(3+)-dependent and
      Fe(3+)-independent manners. Although the Fe(3+)-dependent curcumin potentiation
      results from removal of endogenous inhibitory Fe(3+) at the interface of the
      regulatory (R) domain and intracellular loop (ICL) 3, the molecular mechanism of
      Fe(3+)-independent curcumin potentiation is still unknown. Here, HEK-293T cells
      cultured in an Fe(3+)-containing medium were transiently transfected with CFTR
      constructs, and the role of a highly conserved ICL1/ICL4 interface and a
      stimulatory phosphorylation site S795 or S813 at the C-terminus of the R domain
      in this potentiation pathway was investigated. The results showed that highly
      conserved aromatic and positively charged residues at the ICL1/ICL4 interface and
      phosphorylation site S813 were sensitive to curcumin regardless of whether Fe(3+)
      and nucleotide-binding domain 2 were removed. More importantly, spontaneous
      disulfide cross-linking between curcumin-sensitive ICL1 and S795 was observed to
      be enough to promote channel opening as curcumin did. Therefore, the
      phosphorylated R domain, once released from ICL3, may function as a length- and
      gating-regulatory cross-linker between two transmembrane domains to promote the
      stimulatory interactions between the R domain and the ICL1/ICL4 interface.
      Curcumin may potentiate CFTR activity not only by removing inhibitory Fe(3+) to
      release the R domain from ICL3 but also by stabilizing the stimulatory R
      ICL1/ICL4 interactions. Therefore, the future potentiators with two linked
      aromatic rings could utilize this potentiation pathway to bypass the need for ATP
      to rescue the activity of cystic fibrosis mutants with an ATP-dependent gating
      defect. 

PMID- 25867081
TI  - Improving functional recovery after critical illness.

PMID- 25867082
TI  - Screening method for solvent selection used in tar removal by the absorption
      process.
AB  - The aim of this paper is the study of the treatment of flue gas issued from a
      process of biomass gasification in fluidized bed. The flue gas contains tar which
      should be selectively removed from the fuel components of interest (e.g. H2, CO
      and light hydrocarbons) to avoid condensation and deposits in internal combustion
      engine. The chosen flue gas treatment is the gas-liquid absorption using
      solvents, which present specific physicochemical properties (e.g. solubility,
      viscosity, volatility and chemical and thermal stability) in order to optimize
      the unit on energetic, technico-economic and environmental criteria. The rational
      choice of the proper solvent is essential for solving the tar issue. The
      preselection of the solvents is made using a Hansen parameter in order to
      evaluate the tar solubility and the saturation vapour pressure of the solvent is
      obtained using Antoine law. Among the nine families of screened solvents
      (alcohols, amines, ketones, halogenates, ethers, esters, hydrocarbons, sulphured
      and chlorinates), acids methyl esters arise as solvents of interest. Methyl
      oleate has then been selected and studied furthermore. Experimental liquid-vapour
      equilibrium data using bubbling point and absorption cell measurements and
      theoretical results obtained by the UNIFAC-Dortmund model confirm the high
      potential of this solvent and the good agreement between experimental and
      theoretical results. 

PMID- 25867083
TI  - Scale invariance properties of intracerebral EEG improve seizure prediction in
      mesial temporal lobe epilepsy.
AB  - Although treatment for epilepsy is available and effective for nearly 70 percent
      of patients, many remain in need of new therapeutic approaches. Predicting the
      impending seizures in these patients could significantly enhance their quality of
      life if the prediction performance is clinically practical. In this study, we
      investigate the improvement of the performance of a seizure prediction algorithm
      in 17 patients with mesial temporal lobe epilepsy by means of a novel measure.
      Scale-free dynamics of the intracerebral EEG are quantified through robust
      estimates of the scaling exponents--the first cumulants--derived from a wavelet
      leader and bootstrap based multifractal analysis. The cumulants are investigated
      for the discriminability between preictal and interictal epochs. The performance
      of our recently published patient-specific seizure prediction algorithm is then
      out-of-sample tested on long-lasting data using combinations of cumulants and
      state similarity measures previously introduced. By using the first cumulant in
      combination with state similarity measures, up to 13 of 17 patients had seizures
      predicted above chance with clinically practical levels of sensitivity (80.5%)
      and specificity (25.1% of total time under warning) for prediction horizons above
      25 min. These results indicate that the scale-free dynamics of the preictal state
      are different from those of the interictal state. Quantifiers of these dynamics
      may carry a predictive power that can be used to improve seizure prediction
      performance.

PMID- 25867085
TI  - Molecular and enological characterization of a natural Saccharomyces uvarum and
      Saccharomyces cerevisiae hybrid.
AB  - Saccharomyces cerevisiae plays a main role in the winemaking process, although
      other species, like Saccharomyces uvarum or Saccharomyces paradoxus, have been
      associated with must fermentations. It has been reported in recent years, that
      yeast hybrids of different Saccharomyces species might be responsible for wine
      productions. Although S. cerevisiae*Saccharomyces kudriavzevii hybrids have been
      well studied, very little attention has been paid to S. cerevisiae*S. uvarum
      hybrids. In this work we characterized the genomic composition of S6U, a widely
      used commercial S. cerevisiae*S. uvarum yeast hybrid isolated in wine
      fermentations containing one copy of the genome of each parental species, which
      suggests a relatively recent hybridization event. We also studied its performance
      under diverse enological conditions. The results show enhanced performance under
      low temperature enological conditions, increased glycerol production, lower
      acetic acid production and increased production of interesting aroma compounds.
      We also examined the transcriptomic response of the S6U hybrid strain compared
      with the reference species under enological conditions. The results show that
      although the hybrid strain transcriptome is more similar to S. uvarum than to S.
      cerevisiae, it presents specifically regulated genes involved in stress response,
      lipids and amino acid metabolism. The enological performance and aroma profile of
      this S. cerevisiae*S. uvarum hybrid makes it a good candidate for participating
      in winemaking, especially at low temperatures. 

PMID- 25867084
TI  - Signaling during Kidney Development.
AB  - The kidney plays an essential role during excretion of metabolic waste products,
      maintenance of key homeostasis components such as ion concentrations and hormone
      levels. It influences the blood pressure, composition and volume. The kidney
      tubule system is composed of two distinct cell populations: the nephrons forming
      the filtering units and the collecting duct system derived from the ureteric bud.
      Nephrons are composed of glomeruli that filter the blood to the Bowman's capsule
      and tubular structures that reabsorb and concentrate primary urine. The
      collecting duct is a Wolffian duct-derived epithelial tube that concentrates and
      collects urine and transfers it via the renal pelvis into the bladder. The
      mammalian kidney function depends on the coordinated development of specific cell
      types within a precise architectural framework. Due to the availability of modern
      analysis techniques, the kidney has become a model organ defining the paradigm to
      study organogenesis. As kidney diseases are a problem worldwide, the
      understanding of mammalian kidney cells is of crucial importance to develop
      diagnostic tools and novel therapies. This review focuses on how the pattern of
      renal development is generated, how the inductive signals are regulated and what
      are their effects on proliferation, differentiation and morphogenesis. 

PMID- 25867086
TI  - Locoregionally advanced nasopharyngeal carcinoma in childhood and adolescence:
      Analysis of 95 patients treated with combined chemotherapy and intensity
      modulated radiotherapy.
AB  - BACKGROUND: The purpose of this study was to evaluate the treatment outcomes and
      toxicities of intensity-modulated radiation therapy (IMRT) for children and
      adolescents with locoregionally advanced nasopharyngeal carcinoma (NPC). METHODS:
      Ninety-five patients of <25 years old in locoregionally advanced NPC (stage III
      IVB) were analyzed. All were given neoadjuvant chemotherapy followed by IMRT with
      or without concurrent chemotherapy/adjuvant chemotherapy. RESULTS: The 4-year
      overall survival (OS), locoregional relapse-free survival, progression-free
      survival (PFS), and distant metastasis-free survival (DMFS) were 90.8%, 94.9%,
      79.1%, and 84.0%, respectively. N classification was the only significant
      predicting factor for OS, PFS, and DMFS, with the p value of .017, .015, and
      0.054, respectively. The main long-term complications were xerostomia, hearing
      impairment, and neck fibrosis. CONCLUSION: Neoadjuvant chemotherapy followed by
      IMRT with or without concurrent/adjuvant chemotherapy produced a superb treatment
      outcome in children and adolescents with stage III to IVB disease. Distant
      metastasis was the main failure. More effective treatment strategies are urgently
      needed to further improve the long-term survival. (c) 2015 Wiley Periodicals,
      Inc. Head Neck 38: E665-E672, 2016.

PMID- 25867087
TI  - Precise Determination of the Crystallographic Orientations in Single ZnS
      Nanowires by Second-Harmonic Generation Microscopy.
AB  - We report on the systematical study of the second-harmonic generation (SHG) in
      single zinc sulfide nanowires (ZnS NWs). The high-quality ZnS NWs with round
      cross-section were fabricated by chemical vapor deposition method. The
      transmission electron microscopy images show that the actual growth axis has a
      deviation angle of 0 degrees ~20 degrees  with the preferential growth direction
      [120], which leads to the various polarization-dependent SHG response patterns in
      different individual ZnS NWs. The SHG response is quite sensitive to the
      orientations of c axis as well as the (100) and (010) crystal-axis of ZnS NWs;
      thus, all the three crystal-axis orientations of ZnS NWs are precisely determined
      by the SHG method. A high SHG conversion efficiency of 7 * 10(-6) is obtained in
      single ZnS NWs, which shows potential applications in nanoscale ultraviolet light
      source, nonlinear optical microscopy, and nanophotonic devices. 

PMID- 25867088
TI  - A national assessment of pediatric readiness of emergency departments.
AB  - IMPORTANCE: Previous assessments of readiness of emergency departments (EDs) have
      not been comprehensive and have shown relatively poor pediatric readiness, with a
      reported weighted pediatric readiness score (WPRS) of 55. OBJECTIVES: To assess
      US EDs for pediatric readiness based on compliance with the 2009 guidelines for
      care of children in EDs; to evaluate the effect of physician/nurse pediatric
      emergency care coordinators (PECCs) on pediatric readiness; and to identify gaps
      for future quality initiatives by a national coalition. DESIGN, SETTING, AND
      PARTICIPANTS: Web-based assessment of US EDs (excluding specialty hospitals and
      hospitals without an ED open 24 hours per day, 7 days per week) for pediatric
      readiness. All 5017 ED nurse managers were sent a 55-question web-based
      assessment. Assessments were administered from January 1 through August 23, 2013.
      Data were analyzed from September 12, 2013, through January 11, 2015. MAIN
      OUTCOMES AND MEASURES: A modified Delphi process generated a WPRS. An adjusted
      WPRS was calculated excluding the points received for the presence of physician
      and nurse PECCs. RESULTS: Of the 5017 EDs contacted, 4149 (82.7%) responded,
      representing 24 million annual pediatric ED visits. Among the EDs entered in the
      analysis, 69.4% had low or medium pediatric volume and treated less than 14
      children per day. The median WPRS was 68.9 (interquartile range [IQR] 56.1-83.6).
      The median WPRS increased by pediatric patient volume, from 61.4 (IQR, 49.5-73.6)
      for low-pediatric-volume EDs compared with 89.8 (IQR, 74.7-97.2) for high
      pediatric-volume EDs (P < .001). The median percentage of recommended pediatric
      equipment available was 91% (IQR, 81%-98%). The presence of physician and nurse
      PECCs was associated with a higher adjusted median WPRS (82.2 [IQR, 69.7-92.5])
      compared with no PECC (66.5 [IQR, 56.0-76.9]) across all pediatric volume
      categories (P < .001). The presence of PECCs increased the likelihood of having
      all the recommended components, including a pediatric quality improvement process
      (adjusted relative risk, 4.11 [95% CI, 3.37-5.02]). Barriers to guideline
      implementation were reported by 80.8% of responding EDs. CONCLUSIONS AND
      RELEVANCE: These data demonstrate improvement in pediatric readiness of EDs
      compared with previous reports. The physician and nurse PECCs play an important
      role in pediatric readiness of EDs, and their presence is associated with
      improved compliance with published guidelines. Barriers to implementation of
      guidelines may be targeted for future initiatives by a national coalition whose
      goal is to ensure day-to-day pediatric readiness of our nation's EDs.

PMID- 25867089
TI  - Identification of novel loci associated with gastrointestinal parasite resistance
      in a Red Maasai x Dorper backcross population.
AB  - Gastrointestinal (GI) parasitic infection is the main health constraint for small
      ruminant production, causing loss of weight and/or death. Red Maasai sheep have
      adapted to a tropical environment where extreme parasite exposure is a constant,
      especially with highly pathogenic Haemonchus contortus. This breed has been
      reported to be resistant to gastrointestinal parasite infection, hence it is
      considered an invaluable resource to study associations between host genetics and
      resistance. The aim of this study was to identify polymorphisms strongly
      associated with host resistance in a double backcross population derived from Red
      Maasai and Dorper sheep using a SNP-based GWAS analysis. The animals that were
      genotyped represented the most resistant and susceptible individuals based on the
      tails of phenotypic distribution (10% each) for average faecal egg counts
      (AVFEC). AVFEC, packed cell volume (AVPCV), and live weight (AVLWT) were adjusted
      for fixed effects and co-variables, and an association analysis was run using
      EMMAX. Revised significance levels were calculated using 100,000 permutation
      tests. The top five significant SNP markers with - log10 p-values >3.794 were
      observed on five different chromosomes for AVFEC, and BLUPPf90/PostGSf90 results
      confirmed EMMAX significant regions for this trait. One of these regions included
      a cluster of significant SNP on chromosome (Chr) 6 not in linkage disequilibrium
      to each other. This genomic location contains annotated genes involved in
      cytokine signalling, haemostasis and mucus biosynthesis. Only one association
      detected on Chr 7 was significant for both AVPCV and AVLWT. The results generated
      here reveal candidate immune variants for genes involved in differential response
      to infection and provide additional SNP marker information that has potential to
      aid selection of resistance to gastrointestinal parasites in sheep of a similar
      genetic background to the double backcross population. 

PMID- 25867090
TI  - Rapid identification of chemical genetic interactions in Saccharomyces
      cerevisiae.
AB  - Determining the mode of action of bioactive chemicals is of interest to a broad
      range of academic, pharmaceutical, and industrial scientists. Saccharomyces
      cerevisiae, or budding yeast, is a model eukaryote for which a complete
      collection of ~6,000 gene deletion mutants and hypomorphic essential gene mutants
      are commercially available. These collections of mutants can be used to
      systematically detect chemical-gene interactions, i.e. genes necessary to
      tolerate a chemical. This information, in turn, reports on the likely mode of
      action of the compound. Here we describe a protocol for the rapid identification
      of chemical-genetic interactions in budding yeast. We demonstrate the method
      using the chemotherapeutic agent 5-fluorouracil (5-FU), which has a well-defined
      mechanism of action. Our results show that the nuclear TRAMP RNA exosome and DNA
      repair enzymes are needed for proliferation in the presence of 5-FU, which is
      consistent with previous microarray based bar-coding chemical genetic approaches
      and the knowledge that 5-FU adversely affects both RNA and DNA metabolism. The
      required validation protocols of these high-throughput screens are also
      described. 

PMID- 25867091
TI  - Comments on how Mack et al. (2015) (do not) see iconic memory.
AB  - In a recent paper (Mack et al., 2015) the effect of attentional manipulations on
      partial report performance was investigated. The results were interpreted in
      favor of the stance that an attention-free phenomenal iconic store does not
      exist. Therefore, the authors argue that consciousness requires attention. Here
      we question their conclusions both on the methodological and conceptual grounds. 

PMID- 25867092
TI  - Preparation and testing of plant seed meal-based wood adhesives.
AB  - Recently, the interest in plant seed meal-based products as wood adhesives has
      steadily increased, as these plant raw materials are considered renewable and
      environment-friendly. These natural products may serve as alternatives to
      petroleum-based adhesives to ease environmental and sustainability concerns. This
      work demonstrates the preparation and testing of the plant seed-based wood
      adhesives using cottonseed and soy meal as raw materials. In addition to
      untreated meals, water washed meals and protein isolates are prepared and tested.
      Adhesive slurries are prepared by mixing a freeze-dried meal product with
      deionized water (3:25 w/w) for 2 hr. Each adhesive preparation is applied to one
      end of 2 wood veneer strips using a brush. The tacky adhesive coated areas of the
      wood veneer strips are lapped and glued by hot-pressing. Adhesive strength is
      reported as the shear strength of the bonded wood specimen at break. Water
      resistance of the adhesives is measured by the change in shear strength of the
      bonded wood specimens at break after water soaking. This protocol allows one to
      assess plant seed-based agricultural products as suitable candidates for
      substitution of synthetic-based wood adhesives. Adjustments to the adhesive
      formulation with or without additives and bonding conditions could optimize their
      adhesive properties for various practical applications. 

PMID- 25867093
TI  - Learning the language of time: Children's acquisition of duration words.
AB  - Children use time words like minute and hour early in development, but take years
      to acquire their precise meanings. Here we investigate whether children assign
      meaning to these early usages, and if so, how. To do this, we test their
      interpretation of seven time words: second, minute, hour, day, week, month, and
      year. We find that preschoolers infer the orderings of time words (e.g.,
      hour>minute), but have little to no knowledge of the absolute durations they
      encode. Knowledge of absolute duration is learned much later in development -
      many years after children first start using time words in speech - and in many
      children does not emerge until they have acquired formal definitions for the
      words. We conclude that associating words with the perception of duration does
      not come naturally to children, and that early intuitive meanings of time words
      are instead rooted in relative orderings, which children may infer from their use
      in speech. 

PMID- 25867094
TI  - Pemphigus is associated with KIR3DL2 expression levels and provides evidence that
      KIR3DL2 may bind HLA-A3 and A11 in vivo.
AB  - Although HLA-A3 and A11 have been reported to be ligands for KIR3DL2, evidence
      for any in vivo relevance of this interaction is still missing. To explore the
      functional importance of KIR3DL2 allelic variation, we analyzed the autoimmune
      disease pemphigus foliaceus, previously associated (lower risk) with activating
      KIR genes. KIR3DL2*001 was increased in patients (odds ratio (OR) = 2.04; p =
      0.007). The risk was higher for the presence of both KIR3DL2*001 and HLA-A3 or
      A11 (OR = 3.76, p = 0.013), providing the first evidence that HLA-A3 and A11 may
      interact with KIR3DL2 in vivo. The nonsynonymous single nucleotide polymorphism
      1190T (rs3745902) was associated with protection (OR = 0.52, p = 0.018). This SNP
      results in a threonine-to-methionine substitution. Individuals who have
      methionine in this position exhibit a lower percentage of KIR3DL2-positive
      natural killer (NK) cells and also lower intensity of KIR3DL2 on expressing
      natural killer cells; additionally, we show that the expression of KIR3DL2 is
      independent of other killer cell immunoglobulin-like receptors. Pemphigus
      foliaceus is a very unique complex disease strongly associated with immune
      related genes. It is the only autoimmune disease known to be endemic, showing a
      strong correlation with environmental factors. Our data demonstrate that this
      relatively unknown autoimmune disease may facilitate understanding of the
      molecular mechanisms of KIR3DL2 ligand recognition.

PMID- 25867096
TI  - The effects of low-level laser therapy on condylar growth with a mandibular
      advancement appliance in rats.
AB  - OBJECTIVE: The aim of this study was to evaluate the effects of low-level laser
      therapy (LLLT) on condylar growth with a mandibular advancement appliance in
      rats. BACKGROUND DATA: Researchers studied new methods such as laser, for
      mandibular condyle growth stimulation and acceleration with or without functional
      appliances in experimental animals, but the specific mechanism and laser energy
      density values for condylar biostimulation and bone cell activities are still
      unknown. METHODS: Forty-eight 8-week-old male Wistar albino rats weighing between
      260 and 280 g were randomly divided into four groups. Group I was the control
      group; group II was the mandibular advancement appliance group; group III was the
      8 J/cm(2) (0.25 W, 20 sec) laser irradiation with mandibular advancement
      appliance group; and group IV was the 10 J/cm(2) (0.25 W, 25 sec) laser
      irradiation with mandibular advancement appliance group. Experimental rats in
      groups III and IV were stimulated with a low-level laser in the temporomandibular
      joint region bilaterally 15 times over 30 days. Morphological changes in the
      mandible were evaluated with lateral radiographs before and after the study with
      selected linear and angular measurements. Pearson correlation test, Friedman,
      Kruskal-Wallis, and Mann-Whitney U tests were used for statistical analysis.
      RESULTS: According the lateral radiograph results, the growth of mandibles in the
      experimental groups was significantly more than that of the control group
      (p<0.05). Group III also showed greater mandibular growth than the other groups
      (p<0.05). CONCLUSIONS: We concluded that an intraoral appliance with LLLT,
      including chosen parameters, can stimulate condylar growth and increase
      mandibular advancement.

PMID- 25867095
TI  - Long-term persistence with injectable therapy in relapsing-remitting multiple
      sclerosis: an 18-year observational cohort study.
AB  - Disease modifying therapies (DMTs) reduce the frequency of relapses and
      accumulation of disability in multiple sclerosis (MS). Long-term persistence with
      treatment is important to optimize treatment benefit. This long-term, cohort
      study was conducted at the Calgary MS Clinic. All consenting adults with
      relapsing-remitting MS who started either glatiramer acetate (GA) or interferon
      beta 1a/1b (IFN-beta) between January 1st, 1996 and July 1st, 2011 were included.
      Follow-up continued to February 1st, 2014. Time-to-discontinuation of the initial
      and subsequently-prescribed DMTs (switches) was analysed using Kaplan-Meier
      survival analyses. Group differences were compared using log-rank tests and
      multivariable Cox regression models. Analysis included 1471 participants; 906
      were initially prescribed GA and 565 were initially prescribed IFN-beta. Follow
      up information was available for 87%; 29 (2%) were lost to follow-up and 160
      (11%) moved from Southern Alberta while still using DMT. Median time-to
      discontinuation of all injectable DMTs was 11.1 years. Participants with greater
      disability at treatment initiation, those who started treatment before age 30,
      and those who started between 2006 and 2011 were more likely to discontinue use
      of all injectable DMTs. Median time-to-discontinuation of the initial DMT was 8.6
      years. Those initially prescribed GA remained on treatment longer. Of 610
      participants who discontinued injectable DMT, 331 (54%) started an oral DMT, or a
      second-line DMT, or resumed injectable DMT after 90 days. Persistence with
      injectable DMTs was high in this long-term population-based study. Most
      participants who discontinued injectable DMT did not remain untreated. Further
      research is required to understand treatment outcomes and outcomes after stopping
      DMT. 

PMID- 25867097
TI  - Variation in vital signs resulting from blood component administration in adults.
AB  - BACKGROUND: Although vital signs are routinely recorded before and after every
      transfusion, there are few published data on how these variables vary with
      component administration. Thus, there is very little evidence available to
      support guidelines that are intended to differentiate "benign" changes in vital
      signs from transfusion reactions. The aim of this study was to evaluate the
      variation in vitals observed after transfusion. STUDY DESIGN AND METHODS:
      Retrospective data were extracted from blood bank records for 3496 component
      infusions (red blood cells, n = 2359; platelets, n = 478; plasma, n = 659) over a
      1-year period. The following were collected: recipient pre- and posttransfusion
      vital signs (temperature, pulse rate, and blood pressure) and whether a
      transfusion reaction was reported. RESULTS: Transfusion was associated with very
      mild median changes in temperature (approx. 0  degrees C), pulse rate (<5
      beats/min), or blood pressure (<5 mmHg) across all components. The transfusion
      reaction rate reported by clinical teams was 0.5%, but reported temperature
      changes indicated a higher reaction rate of 2.1% based on institutional criteria.
      CONCLUSIONS: Blood transfusion is not associated with significant changes in
      recipient vital signs. Our data could be used to develop reference ranges for
      transfusion-related vital signs. More than 75% of transfusion reactions may not
      be reported to the blood bank.

PMID- 25867098
TI  - The VCDQ--a Questionnaire for symptom monitoring in vocal cord dysfunction.
AB  - BACKGROUND: Vocal cord dysfunction (VCD) typically involves abnormal adduction of
      the vocal cords during inspiration, mimics the symptoms of asthma and leads to
      the prescription of ineffective medications. OBJECTIVE: We aimed to develop a
      clinical tool to monitor symptoms and response to treatment in confirmed VCD.
      METHODS: We collated symptoms of VCD from focus groups comprising patients and
      healthcare professionals; phrases describing these symptoms were assessed for
      face validity and internal correlation and rated for importance. The resultant 12
      item questionnaire (VCDQ) rated the impact of each on a 5-point Likert scale
      (total score range 12-60) and was tested for reliability, concurrent validity and
      performance in 31 patients with endoscopically confirmed VCD (+/- asthma), 29
      asthmatics with no history of VCD and 14 healthy controls. We assessed response
      to speech and language therapy and the minimal important difference by measuring
      the VCDQ pre- and post- therapy in a 20 new patients. RESULTS: The VCDQ had
      excellent test-retest reliability and differentiated VCD vs. healthy (Mann
      Whitney U-test: z = -5.390, P < 0.001) and asthma (z = -5.730, P < 0.001). All
      patients improved post-therapy, assessed both by a global rating of change score
      (GRCS) and by the VCDQ [median (IQR) score pre-therapy 50.5 (48.0 - 54.8), post
      therapy 35.0 (29.3 - 41.8), P < 0.001]. The minimal important difference in the
      VCDQ associated with a rating of 'minimally better' on the GRCS was 4 points.
      CONCLUSIONS AND CLINICAL RELEVANCE: The VCDQ is a valid and responsive tool
      suitable for measuring changes in symptoms in patients with VCD. It also gives
      insight into which symptoms are important to patients and could guide future
      therapy refinements. Future assessments of novel therapies for this condition
      should use an appropriately validated tool such as the VCDQ to measure response.

PMID- 25867099
TI  - Evolution of DNA aptamers through in vitro metastatic-cell-based systematic
      evolution of ligands by exponential enrichment for metastatic cancer recognition
      and imaging.
AB  - Metastasis, the capability of tumor cells to spread and grow at distant sites, is
      the primary factor in cancer mortality. Because metastasis in sentinel lymph
      nodes suggests the original spread of tumors from a primary site, the detection
      of lymph node involvement with cancer serves as an important prognostic and
      treatment parameter. Here we have developed a panel of DNA aptamers specifically
      binding to colon cancer cell SW620 derived from metastatic site lymph node, with
      high affinity after 14 rounds of selection by the cell-SELEX (systematic
      evolution of ligands by exponential enrichment) method. The binding affinities of
      selected aptamers were evaluated by flow cytometry. Aptamer XL-33 with the best
      binding affinity (0.7 nM) and its truncated sequence XL-33-1 with 45 nt showed
      excellent selectivity for recognizing target cell SW620. The binding entity of
      the selected aptamer has been preliminarily determined as a membrane protein on
      the cell surface. Tissue imaging results showed that XL-33-1 was highly specific
      to the metastatic tumor tissue or lymph node tissue with corresponding cancer
      metastasis and displayed an 81.7% detection rate against colon cancer tissue with
      metastasis in regional lymph nodes. These results suggest that XL-33-1 has great
      potential to become a molecular imaging agent for early detection of lymph node
      tissue with colon cancer metastasis. More importantly, this study clearly
      demonstrates that DNA ligands selectively recognizing metastatic cancer cells can
      be readily generated by metastatic-cell-based SELEX for potential applications in
      metastatic cancer diagnosis and treatment. 

PMID- 25867100
TI  - Comparative analysis of growth and photosynthetic characteristics of (Populus
      simonii * P. nigra) * (P. nigra * P. simonii) hybrid clones of different
      ploidides.
AB  - To evaluate differences among poplar clones of various ploidies, 12 hybrid poplar
      clones (P. simonii * P. nigra) * (P. nigra * P. simonii) with different ploidies
      were used to study phenotypic variation in growth traits and photosynthetic
      characteristics. Analysis of variance showed remarkable differences for each of
      the investigated traits among these clones (P < 0.01). Coefficients of phenotypic
      variation (PCV) ranged from 2.38% to 56.71%, and repeatability ranged from 0.656
      to 0.987. The Pn (photosynthetic rate) photosynthetic photon flux density (PPFD)
      curves of the 12 clones were S-shaped, but the Pn-ambient CO2 (Ca) curves were
      shaped like an inverted "V". The stomatal conductance (Gs)-PPFD and transpiration
      rate (Tr)-PPFD curves had an upward tendency; however, with increasing PFFD, the
      intercellular CO2 concentration (Ci)-PPFD curves had a downward tendency in all
      of the clones. The Pn-PPFD and Pn-Ca curves followed the pattern of a quadratic
      equation. The average light saturation point and light compensation point of the
      triploid clones were the highest and lowest, respectively, among the three types
      of clones. For Pn-Ca curves, diploid clones had a higher average CO2 saturation
      point and average CO2 compensation point compared with triploid and tetraploid
      clones. Correlation analyses indicated that all investigated traits were strongly
      correlated with each other. In future studies, molecular methods should be used
      to analyze poplar clones of different ploidies to improve our understanding of
      the growth and development mechanisms of polyploidy. 

PMID- 25867101
TI  - Adsorption and hydraulic conductivity of landfill-leachate perfluorinated
      compounds in bentonite barrier mixtures.
AB  - Perfluorinated compounds (PFCs) are leached in landfills from a wide range of
      domestic and industrial products. Sodium bentonite, a common barrier material,
      was contacted with water and landfill leachate spiked with PFCs in batch
      adsorption tests to measure PFC adsorption. Leaching cell tests were also
      conducted in which water, landfill leachate and PFC-spiked leachate permeated
      through compacted sand-bentonite mixtures. It was found that the PFCs did not
      bind substantially to the bentonite. Hydraulic conductivities were not
      appreciably affected by the PFCs, showing that bentonite liners are not affected
      for the range of concentrations tested. The sand-bentonite mixture partially
      retained the PFCs, indicating limited effectiveness in containing PFC within
      landfills. 

PMID- 25867102
TI  - Recyclability of bottom ash mixed with dredged soils according to the
      transportation distance and mixing ratio through the estimation of CO2 emissions.
AB  - Bottom ash and dredged soils can be used as construction materials because they
      are similar in physical characteristics to natural aggregates. However, whenever
      such byproducts as bottom ash and dredged soils are used, the energy efficiency
      of recycling is offset to a certain degree by emissions from transportation. The
      objective of this study is to analyze the environmental efficiency of recycling
      bottom ash and dredged soils through the estimation of CO2 emissions, considering
      both transportation distance and the mixing ratio. Agricultural reservoirs were
      selected as the final destinations of these recycled materials. This analysis
      demonstrated that using 100% bottom ash emits less CO2 than using natural
      aggregates when the ash is transported less than 35.15 km. This breakeven
      distance increases exponentially with the mass fraction of admixed dredged soil.
      However, admixture with natural soils does not affect the breakeven distance.
      Using the breakeven distances, the effective area with which it is efficient to
      recycle bottom ash was delineated. When dredged soil is admixed to a mass
      fraction of 70%, the effective area covers most of South Korea. In addition, 100%
      bottom ash was efficient in 1622 reservoirs (9.45%) in terms of CO2 emissions,
      and the mixture with 30% bottom ash and 70% dredged soils is efficient in 98.83%
      of all of the reservoirs in Korea. Bottom ash is most useful for reducing CO2
      emissions when it is mixed with dredged soils, which are a byproduct of
      construction found on-site. This result is meaningful because bottom ash and
      dredged soils are complementary in their physical characteristics, and they need
      to be mixed before use as construction materials. The recycling of bottom ash
      becomes even more attractive with anticipated improvements in fuel efficiency. 

PMID- 25867103
TI  - Kinetics and equilibrium studies on Mg-Al oxide for removal of fluoride in
      aqueous solution and its use in recycling.
AB  - Mg-Al oxide obtained by the thermal decomposition of Mg-Al layered double
      hydroxide (LDH) intercalated with CO3(2-) (CO3.Mg-Al LDH) was found to take up
      fluoride from aqueous solution. Fluoride was removed by rehydration of Mg-Al
      oxide accompanied by combination with F(-). Using five times the stoichiometric
      quantity of Mg-Al oxide, the residual concentration of F was decreased from 100
      to 6.3 mg/L in 480 min, which was below the effluent standard in Japan (8 mg/L).
      Removal of F(-) can be represented by pseudo-second-order reaction kinetics. The
      apparent rate constants at 10  degrees C, 30  degrees C, and 60  degrees C were
      2.3 * 10(-3), 2.2 * 10(-2), and 2.5 * 10(-1) g mmol(-1) min(-1), respectively.
      The apparent activation energy was 73.3 kJ mol(-1). The rate-determining step for
      F removal by Mg-Al oxide was consistent with chemical adsorption involving
      intercalation of F(-) into the reconstructed Mg-Al LDH due to electrostatic
      attraction. The adsorption of F by Mg-Al oxide follows a Langmuir-type
      adsorption. The values of the maximum adsorption and the equilibrium adsorption
      constant were 3.0 mmol g(-1) and 1.1 * 10(3), respectively, for Mg-Al oxide. The
      F(-) in the F.Mg-Al LDH thus produced was found to be anion-exchanged with CO3(2
      ) in solution. The Mg-Al oxide after regeneration treatment had excellent
      properties for removal of F in aqueous solution. In conclusion, the results of
      this study indicated that Mg-Al oxide has potential for use in recycling to
      remove F in aqueous solution. 

PMID- 25867104
TI  - Concentric gel system to study the biophysical role of matrix microenvironment on
      3D cell migration.
AB  - The ability of cells to migrate is crucial in a wide variety of cell functions
      throughout life from embryonic development and wound healing to tumor and cancer
      metastasis. Despite intense research efforts, the basic biochemical and
      biophysical principles of cell migration are still not fully understood,
      especially in the physiologically relevant three-dimensional (3D)
      microenvironments. Here, we describe an in vitro assay designed to allow
      quantitative examination of 3D cell migration behaviors. The method exploits the
      cell's mechanosensing ability and propensity to migrate into previously
      unoccupied extracellular matrix (ECM). We use the invasion of highly invasive
      breast cancer cells, MDA-MB-231, in collagen gels as a model system. The spread
      of cell population and the migration dynamics of individual cells over weeks of
      culture can be monitored using live-cell imaging and analyzed to extract
      spatiotemporally-resolved data. Furthermore, the method is easily adaptable for
      diverse extracellular matrices, thus offering a simple yet powerful way to
      investigate the role of biophysical factors in the microenvironment on cell
      migration. 

PMID- 25867105
TI  - Taking the blame for someone else's wrongdoing: The effects of age and
      reciprocity.
AB  - False confessions are often involved in wrongful convictions and are sometimes
      made to protect someone else (i.e., the guilty), perhaps as a way of
      reciprocating past favors. Experimental research has neglected to investigate
      false confessions made to protect someone else, including among adolescents who
      may be particularly vulnerable given their peer orientation and sensitivity to
      peer influence. The present study examined (a) how often individuals would
      falsely confess to take the blame for another's wrongdoing, and (b) whether the
      willingness to falsely confess would vary by age group and reciprocity. Adult (n
      = 99, M age = 20.29) and adolescent (n = 74, M age = 15.47) participants were
      randomly assigned to either receive or not receive a small favor from a
      confederate, witnessed the confederate cheat on a task, and then decided whether
      to sign a statement taking the blame for the confederate's cheating. Adolescents
      (59%) were more likely to falsely confess than adults (39%). No effect of
      reciprocity was found. Although a well-documented phenomenon in legal cases and
      field studies, the present study provides the first experimental evidence
      concerning voluntary false confessions to protect another, including
      developmental differences in this tendency. Results highlight the vulnerability
      of youth and the potential role of peers in legal decision making.

PMID- 25867106
TI  - Eyewitness identification: Bayesian information gain, base-rate effect
      equivalency curves, and reasonable suspicion.
AB  - We provide a novel Bayesian treatment of the eyewitness identification problem as
      it relates to various system variables, such as instruction effects, lineup
      presentation format, lineup-filler similarity, lineup administrator influence,
      and show-ups versus lineups. We describe why eyewitness identification is a
      natural Bayesian problem and how numerous important observations require careful
      consideration of base rates. Moreover, we argue that the base rate in eyewitness
      identification should be construed as a system variable (under the control of the
      justice system). We then use prior-by-posterior curves and information-gain
      curves to examine data obtained from a large number of published experiments.
      Next, we show how information-gain curves are moderated by system variables and
      by witness confidence and we note how information-gain curves reveal that lineups
      are consistently more proficient at incriminating the guilty than they are at
      exonerating the innocent. We then introduce a new type of analysis that we
      developed called base rate effect-equivalency (BREE) curves. BREE curves display
      how much change in the base rate is required to match the impact of any given
      system variable. The results indicate that even relatively modest changes to the
      base rate can have more impact on the reliability of eyewitness identification
      evidence than do the traditional system variables that have received so much
      attention in the literature. We note how this Bayesian analysis of eyewitness
      identification has implications for the question of whether there ought to be a
      reasonable-suspicion criterion for placing a person into the jeopardy of an
      identification procedure.

PMID- 25867108
TI  - Investigation of hydrodynamic parameters in a draft tube reactor using
      radioisotope based techniques and conventional method.
AB  - In this study, various techniques were attempted to investigate flow dynamics in
      the enclosed reactor and the results from the techniques were compared.
      Radioactive particle tracking (RPT) and industrial single photon emission
      computed tomography (SPECT) were carried out and the circulation times from them
      showed a deviation of 17.5%. The circulation time of the RPT was longer than that
      of SPECT, and it is speculated that the physical dimension of the/ fabricated
      radioactive particle creates the discrepancy. Particle image velocimetry (PIV)
      measurements and computational fluid dynamic (CFD) simulations were conducted.
      The velocity patterns from them were similar to each other in the entire reactor
      region except near the propeller installed at the bottom of the reactor. 

PMID- 25867107
TI  - Metabolic abnormalities of gastrointestinal mucosa in celiac disease: An in vitro
      proton nuclear magnetic resonance spectroscopy study.
AB  - BACKGROUND AND AIM: Celiac disease (CeD) is a common autoimmune disorder in which
      ingestion of gluten and related proteins leads to inflammation in the small
      intestine. Although the histological findings in CeD are characteristic, they are
      not specific. In this study, proton nuclear magnetic resonance (NMR) spectroscopy
      was used to investigate the differences in metabolic profile of duodenal mucosal
      biopsies of patients with CeD and controls to find out the biomarker/s of villous
      atrophy. METHODS: Duodenal mucosal biopsies were collected from 29 CeD patients
      (mean age 26.2 +/- 10.8 years) and 17 controls (mean age 34.1 +/- 11.1 years) and
      were subjected to proton NMR spectroscopy following perchloric acid extraction.
      Assignment of metabolite resonances was carried out and their concentrations were
      determined. For comparison between the groups unpaired t-test/Wilcoxon rank sum
      test was used. Partial least squares-discriminant analysis was performed to study
      the clustering behavior of the samples from CeD patients and controls using the
      Unscrambler 10.2 software. RESULTS: Partial least squares-discriminant analysis
      clearly differentiated CeD patients from controls. Significantly higher
      concentrations of isoleucine, leucine, aspartate, succinate, and pyruvate, and
      lower concentration of glycerophosphocholine, were observed in the duodenal
      mucosa of CeD patients compared with controls. The results suggest abnormalities
      in glycolysis, Krebs cycle (energy deficiency), and amino acid metabolism, which
      may affect the biosynthetic pathways and consequently contribute to villous
      atrophy. CONCLUSIONS: NMR spectroscopy with multivariate analysis of duodenal
      mucosal biopsies revealed a characteristic metabolic profile in CeD patients. The
      work provided an insight in determining biomarker/s for villous atrophy and
      diagnosis of CeD patients.

PMID- 25867109
TI  - meso-Free Corroles: Syntheses, Structures, Properties, and Chemical Reactivities.
AB  - 5,10-Bis(pentafluorophenyl)corrole (5) and 5,15-bis(pentafluorophenyl)corrole (9)
      have been synthesized as meso-free corroles by rational synthetic routes. Both
      the structures of these corroles have been unambiguously revealed by X-ray
      diffraction analysis and their optical and electrochemical properties have been
      studied. Chlorination and oxidative dimerization of 5 and 9 have been explored,
      which revealed a marked different reactivity of the free meso-positions in 5 and
      9. 10-Chlorinated corrole 11 was effectively prepared by the reaction of 9 with
      Palau'chlor in the presence of 1 % pyridine whereas 5-chlorinated corrole 12 was
      obtained in a trace amount from similar chlorination of 5. 5,5'-Linked corrole
      dimer 13 was produced by reaction of 5 with AgNO2 in a good yield, whereas 10,10'
      linked corrole dimer 14 was formed in a moderate yield by the reaction of 9 with
      [bis(trifluoroacetoxy)iodo]benzene. Observed large electronic interaction between
      the two corroles in 13 as compared with that in 14 has been ascribed mainly to
      conformational flexibility of the former, which allows more coplanar
      conformation.

PMID- 25867110
TI  - Fungal enzymes for environmental management.
AB  - Fungal ligninolytic enzymes have broad biotechnological applications.
      Particularly laccases and certain fungal class II peroxidases from white-rot
      basidiomycetes are considered in degradation of persistent organic pollutants.
      Promising processes with reusable immobilized laccases in special reactors have
      been developed up to pilot scale for degradation of pollutants in water.
      Bioremediation of chemically complex soils with their large indigenous microbial
      communities is more difficult. Living fungi and their enzymes are employed.
      Bioaugmentation, introduction of for example white-rots for enzyme production
      into a polluted soil, and biostimulation of suitable resident organisms by
      nutritional manipulations are strategies in degradation of pollutants in soil.
      Bioaugmentation has been successfully implemented on small scale for soils in
      biobeds and for specific materials such as olive mill wastes. 

PMID- 25867111
TI  - Screening for type 2 diabetes mellitus: a systematic review for the U.S.
      Preventive Services Task Force.
AB  - BACKGROUND: Screening for type 2 diabetes mellitus could lead to earlier
      identification and treatment of asymptomatic diabetes, impaired fasting glucose
      (IFG), or impaired glucose tolerance (IGT), potentially resulting in improved
      outcomes. PURPOSE: To update the 2008 U.S. Preventive Services Task Force review
      on diabetes screening in adults. DATA SOURCES: Cochrane databases and MEDLINE
      (2007 through October 2014) and relevant studies from previous Task Force
      reviews. STUDY SELECTION: Randomized, controlled trials; controlled,
      observational studies; and systematic reviews. DATA EXTRACTION: Data were
      abstracted by 1 investigator and checked by a second; 2 investigators
      independently assessed study quality. DATA SYNTHESIS: In 2 trials, screening for
      diabetes was associated with no 10-year mortality benefit versus no screening
      (hazard ratio, 1.06 [95% CI, 0.90 to 1.25]). Sixteen trials consistently found
      that treatment of IFG or IGT was associated with delayed progression to diabetes.
      Most trials of treatment of IFG or IGT found no effects on all-cause or
      cardiovascular mortality, although lifestyle modification was associated with
      decreased risk for both outcomes after 23 years in 1 trial. For screen-detected
      diabetes, 1 trial found no effect of an intensive multifactorial intervention on
      risk for all-cause or cardiovascular mortality versus standard control. In
      diabetes that was not specifically screen-detected, 9 systematic reviews found
      that intensive glucose control did not reduce risk for all-cause or
      cardiovascular mortality and results for intensive blood pressure control were
      inconsistent. LIMITATION: The review was restricted to English-language articles,
      and few studies were conducted in screen-detected populations. CONCLUSION:
      Screening for diabetes did not improve mortality rates after 10 years of follow
      up. More evidence is needed to determine the effectiveness of treatments for
      screen-detected diabetes. Treatment of IFG or IGT was associated with delayed
      progression to diabetes. PRIMARY FUNDING SOURCE: Agency for Healthcare Research
      and Quality.

PMID- 25867112
TI  - Simple visual cues of event boundaries.
AB  - A stream of sensory information is organized into discrete temporal units through
      event segmentation. On the basis of several studies measuring participants'
      explicit decisions about event boundaries, some theorists suggest that this
      segmentation is induced by increased unpredictability. Since this approach cannot
      describe the segmentation of unfamiliar events, we assumed that event
      segmentation might be perceptually driven. We hypothesized that when a new event
      relevant object is represented, it triggers event segmentation. In addition to
      explicit decisions, we measured memory performance, since it has previously been
      found to be a strong indicator of event segmentation. We presented simple videos
      to the participants in which geometric objects were flashing consecutively while
      an unpredictable change occurred. In the New Object condition flashing objects
      were replaced, while in the Same Object condition one non-kind-relevant feature
      of the objects was changed. In Experiment 1 the participants' task was to press a
      button when they detected a meaningful change in the stimuli. In line with the
      predictability-based theories, we found that both changes triggered the detection
      of an event boundary. To contrast our hypothesis with the predictions of earlier
      theories, in Experiments 2 and 3 memory accuracy was measured using the stimuli
      of Experiment 1. We only found a significant change in memory accuracy in the New
      Object condition, which suggests that the appearance of an event-relevant object
      can induce segmentation on its own, and indicates that the explicit-decisions
      methodology might lead to the improper conclusion that event segmentation is
      solely based on predictability. 

PMID- 25867113
TI  - Palladium-catalyzed asymmetric reductive heck reaction of aryl halides.
AB  - Asymmetric reductive Heck reaction of aryl halides is realized in high
      stereoselectivity. Hydrogen-bond donors, trialkylammonium salts in a glycol
      solvent, were used to promote halide dissociation from neutral arylpalladium
      complexes to access cationic, stereoselective pathways. 

PMID- 25867114
TI  - The relation of collapsibility and confounding to faithfulness and stability.
AB  - A probability distribution may have some properties that are stable under a
      structure (e.g., a causal graph) and other properties that are unstable. Stable
      properties are implied by the structure and thus will be shared by populations
      following the structure. In contrast, unstable properties correspond to special
      circumstances that are unlikely to be replicated across those populations. A
      probability distribution is faithful to the structure if all independencies in
      the distribution are logical consequences of the structure. We explore the
      distinction between confounding and noncollapsibility in relation to the concepts
      of faithfulness and stability. Simple collapsibility of an odds ratio over a risk
      factor is unstable and thus unlikely if the exposure affects the outcome, whether
      or not the risk factor is associated with exposure. For a binary exposure with no
      effect, collapsibility over a confounder also requires unfaithfulness.
      Nonetheless, if present, simple collapsibility of the odds ratio limits the
      degree of confounding by the covariate. Collapsibility of effect measures is
      stable if the covariate is independent of the outcome given exposure, but it is
      unstable if the covariate is an instrumental variable. Understanding stable and
      unstable properties of distributions under causal structures, and the distinction
      between stability and faithfulness, yields important insights into the
      correspondence between noncollapsibility and confounding. 

PMID- 25867115
TI  - Vitamin D in Pregnancy and Attention Deficit Hyperactivity Disorder-like Symptoms
      in Childhood.
AB  - BACKGROUND: Vitamin D status during prenatal brain development may influence risk
      of attention deficit and hyperactivity disorder (ADHD) symptoms in childhood.
      However, there are no prospective studies addressing this hypothesis. We aimed to
      examine whether maternal vitamin D status in pregnancy is associated with risk of
      ADHD-like symptoms in offspring. METHODS: We conducted a prospective study
      analyzing data from 1,650 mother-child pairs from five birth cohorts embedded in
      the INMA Project (Spain, 1997-2008). Maternal vitamin D status in pregnancy was
      estimated by measuring plasma concentration of 25-hydroxyvitamin D3 [25(OH)D3] at
      13 weeks of gestation. Children were assessed by teachers for ADHD-like symptoms
      at ages 4-5 years using the Diagnostic and Statistical Manual of Mental Disorders
      ADHD form list. RESULTS: After adjustment, the number of total ADHD-like symptoms
      in children decreased by 11% per 10 ng/ml increment of maternal 25(OH)D3
      concentration (incidence rate ratio [IRR] = 0.89; 95% confidence interval [CI] =
      0.80, 0.98). Similarly, the number of symptoms in the ADHD subscales decreased in
      relation to higher maternal 25(OH)D3 concentration (IRR per 10 ng/ml increment =
      0.89; 95% CI = 0.79, 0.99 for the inattention scale; and IRR = 0.88; 95% CI =
      0.78, 0.99 for the hyperactivity-impulsivity scale). Using diagnostic criteria,
      we found an association of increasing maternal 25(OH)D3 with a lower risk of ADHD
      DSM-IV (relative risk ratio per 10 ng/ml increment = 0.87; 95% CI = 0.72, 1.06)
      and ICD-10 hyperkinetic disorder (relative risk ratio = 0.72; 95% CI = 0.49,
      1.04) in children. CONCLUSION: Higher maternal circulating levels of 25(OH)D3 in
      pregnancy are associated with lower risk of developing ADHD-like symptoms in
      childhood.

PMID- 25867116
TI  - Cost-effectiveness of non-surgical peri-implantitis treatments.
AB  - AIM: The purpose of the present study was to assess the cost-effectiveness of
      various alternatives of non-surgical peri-implantitis treatment. MATERIALS AND
      METHODS: A decision analytical model was constructed and populated with parameter
      estimates from recent literature for reduction in pocket probing depth (PPD) in
      response to eight different treatment alternatives. A micro-costing approach
      combined with an online expert survey was applied to simulate a decision-making
      scenario taking place in Germany. The treatment alternatives providing the most
      advantageous cost/outcome combinations were identified according to the net
      benefit criterion. Uncertainties regarding model input parameters were
      incorporated via simple and probabilistic sensitivity analysis based on Monte
      Carlo simulation. RESULTS: In the base case scenario, debridement alone, Air
      Flow, debridement combined with PerioChip, and debridement combined with local
      antibiotics were identified as treatment strategies with comparably better value
      for money than Er:YAG laser monotherapy, Vector System, debridement combined with
      CHX, and photodynamic therapy. Sensitivity analysis revealed considerable
      decision uncertainty corresponding to limited evidence about different treatment
      alternatives for peri-implantitis treatment. CONCLUSIONS: Derivation of robust
      treatment recommendations for peri-implantitis requires more comprehensive and
      patient-centred evidence on peri-implantitis treatments.

PMID- 25867117
TI  - Age dynamics of DNA damage and CpG methylation in the peripheral blood leukocytes
      of mice.
AB  - Certain types of DNA damage are known to accumulate with age. Here we present the
      quantitative data describing the extent of the spontaneous DNA damage in 144 SHK
      mice of various ages. In each animal, we assessed double strand breaks, single
      strand breaks and alkali-labile sites, as well as amounts of oxidized purines,
      oxidized pyrimidines and misincorporated uracils. In addition, overall levels of
      genome DNA methylation were evaluated. The amounts of oxidized pyrimidines were
      correlated with age in males only, while the amounts of double strand breaks
      (DSB) in DNA samples were correlated with age in females only (R=0.26; p<0.035).
      No age-related accumulation of single-strand breaks (SSB) was observed. The
      hypomethylation of DNA was significant in aging females, but not in aging males.
      Various types of DNA damage were correlated to each other. In attempt to develop
      more stable indicator of age-dependent alterations in DNA, the DNA Damage Level
      Differential (DDLD) indices was developed for comet assaying of peripheral blood
      leukocytes. As expected, DDLD index was shown to be better correlated with age
      than any single quantitative measure reflecting certain type of DNA damage. A
      variability of effectiveness of various kinds of DNA repair in individual animals
      was larger than expected. This conclusion may have a substantial impact on
      subsequent studies of the mutagens and other kinds of environmental stressors in
      animal populations. Nor DDLD neither individual quantitative measures of DNA
      damage were capable of prediction post-sampling survival time. 

PMID- 25867118
TI  - L-Carnitine supplementation decreases DNA damage in treated MSUD patients.
AB  - Maple syrup urine disease (MSUD) is an inherited disorder caused by severe
      deficient activity of the branched-chain alpha-keto acid dehydrogenase complex
      involved in the degradation pathway of branched-chain amino acids (BCAAs) and
      their alpha-ketoacid derivatives. MSUD patients generally present ketoacidosis,
      poor feeding, ataxia, coma, psychomotor delay, mental retardation and brain
      abnormalites. Treatment consists of dietary restriction of the BCAA (low protein
      intake) supplemented by a BCAA-free amino acid mixture. Although the mechanisms
      of brain damage in MSUD are poorly known, previous studies have shown that
      oxidative stress may be involved in the neuropathology of this disorder. In this
      regard, it was recently reported that MSUD patients have deficiency of l
      carnitine (l-car), a compound with antioxidant properties that is used as
      adjuvant therapy in various inborn errors of metabolism. In this work, we
      investigated DNA damage determined by the alkaline comet assay in peripheral
      whole blood leukocytes of MSUD patients submitted to a BCAA-restricted diet
      supplemented or not with l-car. We observed a significant increase of DNA damage
      index (DI) in leukocytes from MSUD patients under BCAA-restricted diet as
      compared to controls and that l-car supplementation significantly decreased DNA
      DI levels. It was also found a positive correlation between DI and MDA content, a
      marker of lipid peroxidation, and an inverse correlation between DI and l-car
      levels. Taken together, our present results suggest a role for reactive species
      and the involvement of oxidative stress in DNA damage in this disorder. Since l
      car reduced DNA damage, it is presumed that dietary supplementation of this
      compound may serve as an adjuvant therapeutic strategy for MSUD patients in
      addition to other therapies. 

PMID- 25867119
TI  - Icariin induces osteogenic differentiation of bone mesenchymal stem cells in a
      MAPK-dependent manner.
AB  - OBJECTIVES: Icariin, a flavonoid isolated from Epimedium pubescens, has
      previously been identified to exert beneficial effects on preventing bone loss
      and promoting bone regeneration. However, molecular mechanisms for its anabolic
      action have, up to now, remained largely unknown. MATERIALS AND METHODS: Effects
      of icariin on cell proliferation and osteogenic differentiation of rat bone
      mesenchymal stem cells (BMSCs) were systematically evaluated. To characterize
      underlying mechanisms, its effects on mitogen-activated protein kinase (MAPK)
      signalling pathways were determined. RESULTS: Results showed that icariin might
      not have enhanced effects on cell proliferation. However, it seemed to
      significantly enhance osteogenic differentiation of BMSCs, demonstrated by
      increasing alkaline phosphatase (ALP) activity and gene expression of collagen
      type I (Col I), osteocalcin (OCN) and osteopotin (OPN). It was demonstrated that
      icariin rapidly phosphorylated extracellular signal-regulated kinase (ERK), p38
      kinase and c-Jun N terminal kinase (JNK). Furthermore, icariin-stimulated
      osteogenic effects on BMSCs were dramatically attenuated by treatment with either
      specific ERK inhibitor of PD98059, p38 inhibitor of SB202190 or JNK inhibitor
      SP600125. CONCLUSIONS: These results provide a potential mechanism of anabolic
      activity of icariin on BMSCs involving ERK, p38 and JNK MAPK pathways.

PMID- 25867120
TI  - Mesopontine median raphe regulates hippocampal ripple oscillation and memory
      consolidation.
AB  - Sharp wave-associated field oscillations (~200 Hz) of the hippocampus, referred
      to as ripples, are believed to be important for consolidation of explicit memory.
      Little is known about how ripples are regulated by other brain regions. We found
      that the median raphe region (MnR) is important for regulating hippocampal ripple
      activity and memory consolidation. We performed in vivo simultaneous recording in
      the MnR and hippocampus of mice and found that, when a group of MnR neurons was
      active, ripples were absent. Consistently, optogenetic stimulation of MnR neurons
      suppressed ripple activity and inhibition of these neurons increased ripple
      activity. Notably, using a fear conditioning procedure, we found that
      photostimulation of MnR neurons interfered with memory consolidation. Our results
      demonstrate a critical role of the MnR in regulating ripples and memory
      consolidation. 

PMID- 25867121
TI  - Therapeutic deep brain stimulation reduces cortical phase-amplitude coupling in
      Parkinson's disease.
AB  - Deep brain stimulation (DBS) is increasingly applied for the treatment of brain
      disorders, but its mechanism of action remains unknown. Here we evaluate the
      effect of basal ganglia DBS on cortical function using invasive cortical
      recordings in Parkinson's disease (PD) patients undergoing DBS implantation
      surgery. In the primary motor cortex of PD patients, neuronal population spiking
      is excessively synchronized to the phase of network oscillations. This manifests
      in brain surface recordings as exaggerated coupling between the phase of the beta
      rhythm and the amplitude of broadband activity. We show that acute therapeutic
      DBS reversibly reduces phase-amplitude interactions over a similar time course as
      that of the reduction in parkinsonian motor signs. We propose that DBS of the
      basal ganglia improves cortical function by alleviating excessive beta phase
      locking of motor cortex neurons. 

PMID- 25867123
TI  - Modulation of human visceral sensitivity by noninvasive magnetoelectrical neural
      stimulation in health and irritable bowel syndrome.
AB  - Visceral pain is a particularly difficult symptom to manage in patients with
      irritable bowel syndrome (IBS). Our aim was to examine whether noninvasive
      neurostimulation applied to the motor cortex or lumbosacral region can modulate
      human visceral sensation. Sixteen healthy adult volunteers and 10 patients with
      IBS were evaluated. Single-pulse lumbosacral magnetic stimulation (LSMS) or
      transcranial magnetic stimulation (TMS) was used to assess spinal root and
      cortical excitability as well as the effect of neurostimulation on anorectal
      sensation and pain, which were provoked by a local electrical stimulus.
      Initially, healthy volunteers received 6 stimulation paradigms in a randomised
      order (3 repetitive LSMS [1 Hz, 10 Hz, and sham]) and 3 repetitive TMS (1 Hz, 10
      Hz, and sham) to investigate the effects on neural function and visceral
      sensation over 1 hour. The most effective cortical and spinal interventions were
      then applied in patients with IBS. Only 1-Hz rLSMS altered healthy anal motor
      excitability, increasing spinal (58 +/- 12.3 vs 38.5 +/- 5.7 MUV, P = 0.04) but
      not cortical responses. Both 1-Hz rLSMS and 10-Hz repetitive transcranial
      magnetic stimulation increased healthy rectal pain thresholds for up to an hour
      after intervention (P < 0.05). When applied to patients with IBS, rectal pain
      thresholds were increased across all time points after both 1-Hz rLSMS and 10-Hz
      repetitive transcranial magnetic stimulation (P < 0.05) compared with sham. The
      application of magnetoelectric stimuli to the cortical and lumbosacral areas
      modulates visceral sensation in healthy subjects and patients with IBS. This
      proof-of-concept study provides supportive evidence for neurostimulation in
      managing functional gastrointestinal disorders. 

PMID- 25867122
TI  - A coding-independent function of an alternative Ube3a transcript during neuronal
      development.
AB  - The E3 ubiquitin ligase Ube3a is an important regulator of activity-dependent
      synapse development and plasticity. Ube3a mutations cause Angelman syndrome and
      have been associated with autism spectrum disorders (ASD). However, the
      biological significance of alternative Ube3a transcripts generated in mammalian
      neurons remains unknown. We report here that Ube3a1 RNA, a transcript that
      encodes a truncated Ube3a protein lacking catalytic activity, prevents exuberant
      dendrite growth and promotes spine maturation in rat hippocampal neurons.
      Surprisingly, Ube3a1 RNA function was independent of its coding sequence but
      instead required a unique 3' untranslated region and an intact microRNA pathway.
      Ube3a1 RNA knockdown increased activity of the plasticity-regulating miR-134,
      suggesting that Ube3a1 RNA acts as a dendritic competing endogenous RNA.
      Accordingly, the dendrite-growth-promoting effect of Ube3a1 RNA knockdown in vivo
      is abolished in mice lacking miR-134. Taken together, our results define a
      noncoding function of an alternative Ube3a transcript in dendritic protein
      synthesis, with potential implications for Angelman syndrome and ASD. 

PMID- 25867124
TI  - Development and preliminary validation of an integrated efficacy-tolerability
      composite measure for the evaluation of analgesics.
AB  - The goal of this analysis was to develop and evaluate integrated measures of
      benefit and tolerability of analgesic drugs in clinical trials. We evaluated an
      efficacy-tolerability composite (ETC) measure combining different cutoff values
      for daily pain reduction (>=20%, >=30%, or >=50% pain reduction) and adverse
      events (AEs) (no AE, no or mild AEs, no or mild drug-related AEs). Nine ETC
      cutoff values (3 * 3) were tested using data from a randomized double-blind trial
      comparing tapentadol extended release (ER) (n = 310), oxycodone controlled
      release (CR) (n = 322), and placebo (n = 314) in subjects with chronic low back
      pain. Efficacy-tolerability composite scores were calculated as the mean number
      of days a subject met the ETC criterion divided by the number of days the subject
      was expected to be in study; ETC scores were then averaged in each treatment
      group. For all 9 ETC measures, validity was demonstrated by significant
      correlation of ETC scores with patients' Global Impression of change and with
      change from baseline in pain scores. Tapentadol ER ETC scores were statistically
      significantly higher than oxycodone CR ETC scores for 4 of the ETC measures.
      "No/mild drug-related AE and >=20% pain reduction" demonstrated the best overall
      validity (correlation with patients' global impression of change) and
      responsiveness (discrimination between treatment groups), yielding a higher
      standardized effect size for tapentadol ER compared with placebo (0.19 [95%
      confidence interval: 0.031-0.346]) and with oxycodone CR (0.23 [95% confidence
      interval: 0.070-0.383]) than other cutoff values. Thus, we have identified herein
      a composite measure that seems to be a valid and responsive measure of the
      overall efficacy and tolerability of analgesics in clinical trials. 

PMID- 25867125
TI  - Tricyclic antidepressants and opioids-better together?

PMID- 25867126
TI  - Problem with defining headache etiology using patient symptomatology.

PMID- 25867127
TI  - Non-invasive parenchymal, vascular and metabolic high-frequency ultrasound and
      photoacoustic rat deep brain imaging.
AB  - Photoacoustics and high frequency ultrasound stands out as powerful tools for
      neurobiological applications enabling high-resolution imaging on the central
      nervous system of small animals. However, transdermal and transcranial
      neuroimaging is frequently affected by low sensitivity, image aberrations and
      loss of space resolution, requiring scalp or even skull removal before imaging.
      To overcome this challenge, a new protocol is presented to gain significant
      insights in brain hemodynamics by photoacoustic and high-frequency ultrasounds
      imaging with the animal skin and skull intact. The procedure relies on the
      passage of ultrasound (US) waves and laser directly through the fissures that are
      naturally present on the animal cranium. By juxtaposing the imaging transducer
      device exactly in correspondence to these selected areas where the skull has a
      reduced thickness or is totally absent, one can acquire high quality deep images
      and explore internal brain regions that are usually difficult to anatomically or
      functionally describe without an invasive approach. By applying this experimental
      procedure, significant data can be collected in both sonic and optoacoustic
      modalities, enabling to image the parenchymal and the vascular anatomy far below
      the head surface. Deep brain features such as parenchymal convolutions and
      fissures separating the lobes were clearly visible. Moreover, the configuration
      of large and small blood vessels was imaged at several millimeters of depth, and
      precise information were collected about blood fluxes, vascular stream velocities
      and the hemoglobin chemical state. This repertoire of data could be crucial in
      several research contests, ranging from brain vascular disease studies to
      experimental techniques involving the systemic administration of exogenous
      chemicals or other objects endowed with imaging contrast enhancement properties.
      In conclusion, thanks to the presented protocol, the US and PA techniques become
      an attractive noninvasive performance-competitive means for cortical and internal
      brain imaging, retaining a significant potential in many neurologic fields. 

PMID- 25867128
TI  - The pain and stress of wound treatment in patients with burns: an international
      burn specialist perspective.
AB  - This study aimed to explore the views of burn specialists on the importance of
      reducing stress and pain during wound treatment. METHODS: Burns specialists were
      invited to complete an online survey, consisting of 10 questions about pain and
      stress in their patients. RESULTS: There were 141 respondents from 39 countries.
      Most were European (54.9%), and the majority were surgeons (71.8%). Pain-free and
      stress-free dressing changes were viewed as important overall ('very important:'
      47.5% and 40.8%, respectively), although, in both cases, 11.3% did not view
      either to be important. Respondents identified 7 benefits of simple, pain-free
      dressing removal, although the focus was on clinical advantages rather than being
      patient-centered. Although most acknowledged that pain is linked with stress,
      disagreement levels ranged from 21.9% to 25.3%. Additionally, only 22.5% agreed
      that stress is related to wound healing. CONCLUSION: In general, burn specialists
      recognized that pain can lead to stress and that it is important to reduce stress
      and pain at dressing changes. Most also acknowledged that stress can affect wound
      healing. However, these results suggest a need for research to further explore
      perceptions about pain and stress, and how these perceptions can impact wound
      management regimes.

PMID- 25867129
TI  - Patients' experience of advanced wound treatment-a qualitative study.
AB  - INTRODUCTION: Each patient experiences wound treatment differently, and it is
      important to enhance the knowledge of the impact of the treatment to be able to
      individualize patient care. METHODS: This descriptive qualitative study aims to
      describe the experience of patients with wounds treated with advanced moist wound
      therapy (AMWT) and negative pressure wound therapy (NPWT). Data were collected
      from 15 diaries written by patients during their treatment, and analyzed with
      content analysis. RESULTS: The results identified an overall theme of "threat to
      normality," and 3 subcategories including "impact on daily life,"
      "manageability," and "powerlessness." CONCLUSION: While there were many
      similarities in the descriptions of the patients in the 2 groups, there also were
      unique features for each treatment group. For patients treated with AMWT, the
      main concern was pain. For patients treated with NPWT, the main concern was the
      optimal functioning of the machine. Patients undergoing wound treatment have
      different focuses, concerns, and needs related to treatment modality. It is
      important for health care personnel to carry this in mind to be able to
      individualize patient care.    .

PMID- 25867130
TI  - Significant reduction of symptoms of scarring with electrical stimulation:
      evaluated with subjective and objective assessment tools in a prospective
      noncontrolled case series.
AB  - INTRODUCTION: Fenzian wave (FW) electrical stimulation has been shown to
      influence cutaneous wound healing. The authors previously published a case series
      investigating the effect of FW on symptomatic abnormal skin scars (raised dermal
      scars [RDS]) using spectrophotometric intracutaneous analysis (SIAscopy). In
      addition, a human volunteer sequential biopsy study in acute cutaneous wounds was
      conducted, which demonstrated that FW increased vascularity. The aim of this
      study was to evaluate the effectiveness of FW on symptomatic RDS using full-field
      laser perfusion imaging (FLPI) to assess changes in dermal blood flow. METHODS:
      Eighteen patients with RDS and long-term pain and pruritus participated.Time
      points analyzed were day 0, weeks 1 and 2, and months 1 and 2. Symptoms were
      monitored using a subjective numerical rating scale. Additionally, a Manchester
      Scar Scale and digital photographywere used. Objective noninvasive measures
      captured quantitative data: SIAscopy to measure melanin, hemoglobin and collagen
      levels, and FLPI to assess the dermal blood flow. RESULTS: There were
      statistically significant reductions in pain scores (from day 0 to month 1, P =
      0.007) and pruritus scores (from day 0 to week 1, P = 0.007; and day 0 to month
      1, P = 0.002). The trend for melanin levels demonstrated an increase from day 0
      to week 1, hemoglobin levels showed an increase from day 0 to week 2, and
      hemoglobin flux increased from day 0 to week 2 (not statistically significant).
      CONCLUSION: This report demonstrates that FW electrical stimulation significantly
      reduces the symptoms of pain and pruritus in patients with RDS. This unique
      treatment has the potential for management of symptomatic skin scarring.  .

PMID- 25867131
TI  - In vitro antimicrobial efficacy of a silver-containing wound dressing against
      mycobacteria associated with atypical skin ulcers.
AB  - Mycobacterium ulcerans, the etiological agent in Buruli and related ulcers, is a
      major threat to public health in many tropical countries. Recommended treatment
      that is accessible and affordable for affected individuals includes surgical
      debridement and combination antibiotics. The potential benefits in the use of
      antimicrobial wound dressings has not been demonstrated to date, and consequently
      the efficacy of a silver-containing absorbent dressing was investigated against a
      pathogenic wound mycobacterium using stringent in vitro models. The in vitro
      models were designed to simulate a variety of challenging wound conditions.
      Mycobacterium fortuitum was used as a fast-growing surrogate for M. ulcerans, a
      physiologically similar but slower-growing and more significant wound pathogen.
      Collectively, the studies showed that the silver-containing dressing was
      bactericidal against M. fortuitum, it maintained killing effect over a prolonged
      period (7 days) under conditions simulating excessive exudate, and killed an
      average of 100% of the bacterial population inoculated directly beneath the
      dressing in a simulated, colonized, shallow wound model. Based on the in vitro
      data generated in the current research, use of the silver-containing dressing as
      part of a protocol-of-care in the management of Buruli and related ulcers may
      help to alleviate wound infection caused by pathogenic mycobacteria, improve
      quality of life, and provide infection protection in endemic and at-risk regions.
      . 

PMID- 25867132
TI  - Imaging local Ca2+ signals in cultured mammalian cells.
AB  - Cytosolic Ca2+ ions regulate numerous aspects of cellular activity in almost all
      cell types, controlling processes as wide-ranging as gene transcription,
      electrical excitability and cell proliferation. The diversity and specificity of
      Ca2+ signaling derives from mechanisms by which Ca2+ signals are generated to act
      over different time and spatial scales, ranging from cell-wide oscillations and
      waves occurring over the periods of minutes to local transient Ca2+ microdomains
      (Ca2+ puffs) lasting milliseconds. Recent advances in electron multiplied CCD
      (EMCCD) cameras now allow for imaging of local Ca2+ signals with a 128 x 128
      pixel spatial resolution at rates of >500 frames sec(-1) (fps). This approach is
      highly parallel and enables the simultaneous monitoring of hundreds of channels
      or puff sites in a single experiment. However, the vast amounts of data generated
      (ca. 1 Gb per min) render visual identification and analysis of local Ca2+ events
      impracticable. Here we describe and demonstrate the procedures for the
      acquisition, detection, and analysis of local IP3-mediated Ca2+ signals in intact
      mammalian cells loaded with Ca2+ indicators using both wide-field epi
      fluorescence (WF) and total internal reflection fluorescence (TIRF) microscopy.
      Furthermore, we describe an algorithm developed within the open-source software
      environment Python that automates the identification and analysis of these local
      Ca2+ signals. The algorithm localizes sites of Ca2+ release with sub-pixel
      resolution; allows user review of data; and outputs time sequences of
      fluorescence ratio signals together with amplitude and kinetic data in an Excel
      compatible table.

PMID- 25867133
TI  - Retrospective study comparing healthcare costs and utilization between
      commercially insured patients with type 2 diabetes mellitus who are newly
      initiating exenatide once weekly or liraglutide in the United States.
AB  - OBJECTIVE: To compare healthcare costs and utilization between commercially
      insured patients with type 2 diabetes mellitus (T2DM) in the United States newly
      initiating exenatide once weekly (QW) or liraglutide. METHODS: This retrospective
      cohort study used US administrative claims data to study patients with T2DM
      initiating exenatide QW or liraglutide (initiated therapy = index therapy).
      Patients were included if they had T2DM, were glucagon-like peptide-1 receptor
      agonist (GLP-1RA) naive, initiated exenatide QW or liraglutide from 1 February
      2012 to 1 October 2012 (date of initiation = index), were >=18 years at index,
      and had continuous enrollment for 12 months before (baseline) to 6 months after
      index (follow-up). Study outcomes were overall and diabetes-specific healthcare
      utilization and costs. Multivariable regressions compared the study outcomes
      between exenatide QW and liraglutide, adjusting for potential confounders.
      Sensitivity analyses were performed to assess liraglutide by dose (1.2 mg/1.8
      mg). RESULTS: The study sample included 9106 liraglutide (4188, 1.2 mg; 4918, 1.8
      mg) patients and 2445 exenatide QW patients. In multivariable-adjusted analyses,
      compared with liraglutide patients, exenatide QW patients had statistically
      significantly lower odds of overall inpatient admissions (odds ratio [OR] = 0.80,
      p = 0.046) and diabetes-specific (OR = 0.83, p = 0.026) inpatient admissions,
      similar overall total costs ($7833 exenatide QW, $8296 liraglutide, p = 0.069)
      and diabetes-specific total costs ($3610 exenatide QW, $3736 liraglutide, p =
      0.298), and statistically significantly lower overall medical costs ($3939
      exenatide QW, $4652 liraglutide, p = 0.008) and diabetes-specific medical costs
      ($1161 exenatide QW, $1469 liraglutide, p = 0.007). Sensitivity analyses
      assessing liraglutide by dose were directionally consistent. Unadjusted
      exploratory analyses showed that exenatide QW patients obtained a greater median
      number of days supplied for their GLP-1RA during follow-up (141 days) than
      liraglutide patients (124 days). CONCLUSIONS: In this 6 month follow-up study,
      patients receiving exenatide QW had similar total healthcare costs but lower odds
      of inpatient admission and lower medical costs compared with patients receiving
      liraglutide.

PMID- 25867134
TI  - Monitoring the quality consistency of Weibizhi tablets by micellar electrokinetic
      chromatography fingerprints combined with multivariate statistical analyses, the
      simple quantified ratio fingerprint method, and the fingerprint-efficacy
      relationship.
AB  - Micellar electrokinetic chromatography fingerprinting combined with
      quantification was successfully developed and applied to monitor the quality
      consistency of Weibizhi tablets, which is a classical compound preparation used
      to treat gastric ulcers. A background electrolyte composed of 57 mmol/L sodium
      borate, 21 mmol/L sodium dodecylsulfate and 100 mmol/L sodium hydroxide was used
      to separate compounds. To optimize capillary electrophoresis conditions,
      multivariate statistical analyses were applied. First, the most important factors
      influencing sample electrophoretic behavior were identified as background
      electrolyte concentrations. Then, a Box-Benhnken design response surface strategy
      using resolution index RF as an integrated response was set up to correlate
      factors with response. RF reflects the effective signal amount, resolution, and
      signal homogenization in an electropherogram, thus, it was regarded as an
      excellent indicator. In fingerprint assessments, simple quantified ratio
      fingerprint method was established for comprehensive quality discrimination of
      traditional Chinese medicines/herbal medicines from qualitative and quantitative
      perspectives, by which the quality of 27 samples from the same manufacturer were
      well differentiated. In addition, the fingerprint-efficacy relationship between
      fingerprints and antioxidant activities was established using partial least
      squares regression, which provided important medicinal efficacy information for
      quality control. The present study offered an efficient means for monitoring
      Weibizhi tablet quality consistency. 

PMID- 25867135
TI  - Translation and validation of the Danish version of the postoperative quality of
      recovery score QoR-15.
AB  - BACKGROUND: Patient perceived quality of recovery is an important outcome after
      surgery and should be measured in clinical trials. Quality of recovery after
      surgery and general anaesthesia can be measured by the QoR-15. A high score
      indicates a good recovery and the score ranges from 0 to 150. The aim of this
      study was to translate the QoR-15 questionnaire into Danish and do a full
      psychometric evaluation of the Danish version. METHODS: A translation and
      cultural adaption of the original version of the QoR-15 into a Danish version,
      the QoR-15D, was performed. After obtaining consent, patients undergoing elective
      abdominal, orthopaedic or gynaecological surgery under general anaesthesia were
      included. Patients completed the QoR-15D before surgery and on the first
      postoperative day. The validity, reliability, responsiveness and clinical
      feasibility of the QoR-15D were evaluated. RESULTS: One hundred and forty
      patients returned their pre- and postoperative questionnaire successfully giving
      a completion rate of 56%. The postoperative QoR-15 score was negatively
      correlated with duration of surgery (rho = -0.21, 95% CI: -0.04 to -0.36, P <
      0.02) and postoperative stay (rho = -0.28, 95% CI: -0.12 to -0.43, P < 0.01).
      Postoperative QoR-15D scores were inversely related to the extent of surgery:
      minor, intermediate or major (127 +/- 22, 106 +/- 29 and 96 +/- 24, respectively,
      P < 0.01). Cronbach's alpha and split-half reliability was 0.90 and 0.88. Test
      retest reliability was 0.99 (95% CI: 0.94-1.00). Cohen's effect size was 1.13 and
      the standardized response mean was 0.82. CONCLUSION: The QoR-15D has preserved
      the validity, excellent reliability, high degree of responsiveness and the
      clinical feasibility of the original English version.

PMID- 25867137
TI  - When Rate Constants Are Not Enough.
AB  - Real-world chemical systems consisting of multiple isomers and multiple reaction
      channels often react significantly prior to attaining a steady state energy
      distribution (SED). Detailed elementary reaction models, which implicitly require
      SED conditions, may be invalid when non-steady-state energy distributions (NSED)
      exist. NSED conditions may result in reaction rates and product yields that are
      different from those expected for SED conditions, although this problem is to
      some extent reduced by using phenomenological models and rate constants. The
      present study defines pragmatic diagnostics useful for identifying NSED
      conditions in stochastic master equation simulations. A representative example is
      presented for each of four classes of common combustion species: RO2 radicals,
      aliphatic hydrocarbons, alkyl radicals, and polyaromatic radicals. An example
      selected from the seminal work of Tsang et al. demonstrates that stochastic
      simulations and eigenvalue methods for solving the master equation predict the
      same NSED effects. NSED effects are common under relatively moderate combustion
      conditions, and accurate simulations may require a master equation analysis. 

PMID- 25867136
TI  - Methods for culturing human femur tissue explants to study breast cancer cell
      colonization of the metastatic niche.
AB  - Bone is the most common site of breast cancer metastasis. Although it is widely
      accepted that the microenvironment influences cancer cell behavior, little is
      known about breast cancer cell properties and behaviors within the native
      microenvironment of human bone tissue.We have developed approaches to track,
      quantify and modulate human breast cancer cells within the microenvironment of
      cultured human bone tissue fragments isolated from discarded femoral heads
      following total hip replacement surgeries. Using breast cancer cells engineered
      for luciferase and enhanced green fluorescent protein (EGFP) expression, we are
      able to reproducibly quantitate migration and proliferation patterns using
      bioluminescence imaging (BLI), track cell interactions within the bone fragments
      using fluorescence microscopy, and evaluate breast cells after colonization with
      flow cytometry. The key advantages of this model include: 1) a native,
      architecturally intact tissue microenvironment that includes relevant human cell
      types, and 2) direct access to the microenvironment, which facilitates rapid
      quantitative and qualitative monitoring and perturbation of breast and bone cell
      properties, behaviors and interactions. A primary limitation, at present, is the
      finite viability of the tissue fragments, which confines the window of study to
      short-term culture. Applications of the model system include studying the basic
      biology of breast cancer and other bone-seeking malignancies within the
      metastatic niche, and developing therapeutic strategies to effectively target
      breast cancer cells in bone tissues. 

PMID- 25867138
TI  - Organotypic slice cultures for studies of postnatal neurogenesis.
AB  - Here we describe a technique for studying hippocampal postnatal neurogenesis in
      the rodent brain using the organotypic slice culture technique. This method
      maintains the characteristic topographical morphology of the hippocampus while
      allowing direct application of pharmacological agents to the developing
      hippocampal dentate gyrus. Additionally, slice cultures can be maintained for up
      to 4 weeks and thus, allow one to study the maturation process of newborn granule
      neurons. Slice cultures allow for efficient pharmacological manipulation of
      hippocampal slices while excluding complex variables such as uncertainties
      related to the deep anatomic location of the hippocampus as well as the blood
      brain barrier. For these reasons, we sought to optimize organotypic slice
      cultures specifically for postnatal neurogenesis research. 

PMID- 25867141
TI  - Dissociating conscious expectancies from automatic link formation in associative
      learning: a review on the so-called Perruchet effect.
AB  - A long-running debate in the literature on conditioning in humans focuses on the
      question of whether conditioned responses are the product of automatic link
      formation processes governed by the standard laws of simple associative learning,
      or the consequence of participants' inferences about the relationships between
      the 2 related events, E1 and E2, which would lead E1 to generate a conscious
      expectancy of E2. A paradigm aimed at dissociating the predictions of the 2
      accounts was proposed by Perruchet (1985). In this paradigm, E2 randomly follows
      E1 only half of the time on average, a probability that is known to participants.
      When the preceding run goes from a long sequence of E1 alone to a long sequence
      of E1-E2 pairs, associative strength should increase, whereas conscious
      expectancy for E2 should decrease in keeping with the gambler's fallacy. This
      article reviews the studies making use of the paradigm in the classical
      conditioning domain, and the extension of the same logic to a few other
      experimental situations. Overall, overt behavior has been found to change in line
      with associative strength, and in opposition to conscious expectancy, attesting
      to an empirical dissociation of automatic and control processes within a single
      preparation. The paradigm, however, is endowed with a number of tricky
      methodological issues, which are examined each in turn. Although some of these
      issues call for further research, a tentative conclusion is that the effect
      provides evidence for automatic link formation processes, the existence of which
      has been recently denied in the "propositional" account of learning.

PMID- 25867140
TI  - Functional reconstitution and channel activity measurements of purified wildtype
      and mutant CFTR protein.
AB  - The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) is a unique
      channel-forming member of the ATP Binding Cassette (ABC) superfamily of
      transporters. The phosphorylation and nucleotide dependent chloride channel
      activity of CFTR has been frequently studied in whole cell systems and as single
      channels in excised membrane patches. Many Cystic Fibrosis-causing mutations have
      been shown to alter this activity. While a small number of purification protocols
      have been published, a fast reconstitution method that retains channel activity
      and a suitable method for studying population channel activity in a purified
      system have been lacking. Here rapid methods are described for purification and
      functional reconstitution of the full-length CFTR protein into proteoliposomes of
      defined lipid composition that retains activity as a regulated halide channel.
      This reconstitution method together with a novel flux-based assay of channel
      activity is a suitable system for studying the population channel properties of
      wild type CFTR and the disease-causing mutants F508del- and G551D-CFTR.
      Specifically, the method has utility in studying the direct effects of
      phosphorylation, nucleotides and small molecules such as potentiators and
      inhibitors on CFTR channel activity. The methods are also amenable to the study
      of other membrane channels/transporters for anionic substrates. 

PMID- 25867142
TI  - Asymmetries in time-based and feature-based discriminations in humans: linking
      the long+ and feature-positive effects.
AB  - Three experiments examined time-based and feature-based discrimination learning
      in a video game task with human participants. Each participant played the role of
      gunner on a space ship. Participants were told that a periodically presented
      target object might or might not be hiding an enemy alien, which would appear
      briefly once the target disappeared. Points were given for 'shooting' at the
      target that hid the enemy alien, and were taken away if the target was ultimately
      not hiding an alien. In Experiment 1, either a relatively long (4 s) or a
      relatively short (1 s) intertrial interval (ITI) predicted whether an alien would
      be hiding behind the next target. Participants anticipated enemy aliens more
      readily when the long ITI predicted the enemy alien than when the short ITI did
      so, establishing a long+ effect for the first time in humans. In Experiment 2, a
      friendly alien was added on the negative trials, so that a different event,
      rather than no event, occurred on the negative trials. This eliminated the long+
      effect; that is, participants now found it equally easy to predict the target
      enemy aliens whether they uniquely followed long or short ITIs. Experiment 3
      examined whether a similar treatment reduced the theoretically related feature
      positive (FP) effect. In that experiment, a unique visual image, rather than the
      ITI duration, served as the predictor. An FP effect occurred when the
      discrimination was between trials with an outcome versus no outcome, but not when
      the discrimination was between an outcome versus a different outcome. The
      findings connect the long+ and the FP effects, and suggest that both can be
      reduced by making the negative trials more salient.

PMID- 25867139
TI  - Randomized phase II/III clinical trial of elpamotide for patients with advanced
      pancreatic cancer: PEGASUS-PC Study.
AB  - Gemcitabine is a key drug for the treatment of pancreatic cancer; however, with
      its limitation in clinical benefits, the development of another potent
      therapeutic is necessary. Vascular endothelial growth factor receptor 2 is an
      essential target for tumor angiogenesis, and we have conducted a phase I clinical
      trial using gemcitabine and vascular endothelial growth factor receptor 2 peptide
      (elpamotide). Based on the promising results of this phase I trial, a
      multicenter, randomized, placebo-controlled, double-blind phase II/III clinical
      trial has been carried out for pancreatic cancer. The eligibility criteria
      included locally advanced or metastatic pancreatic cancer. Patients were assigned
      to either the Active group (elpamotide + gemcitabine) or Placebo group (placebo +
      gemcitabine) in a 2:1 ratio by the dynamic allocation method. The primary
      endpoint was overall survival. The Harrington-Fleming test was applied to the
      statistical analysis in this study to evaluate the time-lagged effect of
      immunotherapy appropriately. A total of 153 patients (Active group, n = 100;
      Placebo group, n = 53) were included in the analysis. No statistically
      significant differences were found between the two groups in the prolongation of
      overall survival (Harrington-Fleming P-value, 0.918; log-rank P-value, 0.897;
      hazard ratio, 0.87, 95% confidence interval [CI], 0.486-1.557). Median survival
      time was 8.36 months (95% CI, 7.46-10.18) for the Active group and 8.54 months
      (95% CI, 7.33-10.84) for the Placebo group. The toxicity observed in both groups
      was manageable. Combination therapy of elpamotide with gemcitabine was well
      tolerated. Despite the lack of benefit in overall survival, subgroup analysis
      suggested that the patients who experienced severe injection site reaction, such
      as ulceration and erosion, might have better survival. 

PMID- 25867143
TI  - Morphology-Controlled Synthesis of Au/Cu2FeSnS4 Core-Shell Nanostructures for
      Plasmon-Enhanced Photocatalytic Hydrogen Generation.
AB  - Copper-based chalcogenides of earth-abundant elements have recently arisen as an
      alternate material for solar energy conversion. Cu2FeSnS4 (CITS), a quaternary
      chalcogenide that has received relatively little attention, has the potential to
      be developed into a low-cost and environmentlly friendly material for
      photovoltaics and photocatalysis. Herein, we report, for the first time, the
      synthesis, characterization, and growth mechanism of novel Au/CITS core-shell
      nanostructures with controllable morphology. Precise manipulations in the core
      shell dimensions are demonstrated to yield two distinct heterostructures with
      spherical and multipod gold nanoparticle (NP) cores (Au(sp)/CITS and
      Au(mp)/CITS). In photocatalytic hydrogen generation with as-synthesized Au/CITS
      NPs, the presence of Au cores inside the CITS shell resulted in higher hydrogen
      generation rates, which can be attributed to the surface plasmon resonance (SPR)
      effect. The Au(sp)/CITS and Au(mp)/CITS core-shell NPs enhanced the
      photocatalytic hydrogen generation by about 125% and 240%, respectively, compared
      to bare CITS NPs.

PMID- 25867145
TI  - Stem cell transplantation as rescue therapy for refractory Crohn's disease: a
      sytematic review.
AB  - BACKGROUND: Crohn's disease is a chronic relapsing- remitting affection. It has a
      strong immunologic component which represent the target of standard therapies
      including immunosppressants and biological therapies. However, many patients
      remain refracory or intolerant to these therapies. AIM: The aim of this review is
      to determine the effects of stem cell transplantation in patients with refractory
      Crohn's disease. METHODS: Systematic review of observational studies, clinical
      trials and case reports that focused on the effectiveness and safety of stem cell
      transplantation in patients with refractory Crohn's disease. RESULTS:
      Hematopoietic stem cell transplantation seems to be efficient in maintaining
      clinical and endoscopic remission in patients with Crohn's disease refractory or
      intolerant to current therapies. However, it has been associated to high
      morbidity and mortality due to chemotherapy. Mesenchymal stem cell
      transplantation could induce remission in patients with fistulising refractory
      Crohns disease with no severe side effects. Its impact on luminal Crohns disease
      is still controversial. CONCLUSION: Stem cell transplantation seems to hold
      promising in patients with refractory Crohn's disease. However, because of the
      high morbidity and mortality related to chemotherapy, hematopoietic stem cell
      transplantation should be used as last resort to control this disease.
      Effectiveness of mesenchymal stem cell transplantation in luminal Crohn's disease
      has yet to be proven.

PMID- 25867144
TI  - Sealable femtoliter chamber arrays for cell-free biology.
AB  - Cell-free systems provide a flexible platform for probing specific networks of
      biological reactions isolated from the complex resource sharing (e.g., global
      gene expression, cell division) encountered within living cells. However, such
      systems, used in conventional macro-scale bulk reactors, often fail to exhibit
      the dynamic behaviors and efficiencies characteristic of their living micro-scale
      counterparts. Understanding the impact of internal cell structure and scale on
      reaction dynamics is crucial to understanding complex gene networks. Here we
      report a microfabricated device that confines cell-free reactions in cellular
      scale volumes while allowing flexible characterization of the enclosed molecular
      system. This multilayered poly(dimethylsiloxane) (PDMS) device contains
      femtoliter-scale reaction chambers on an elastomeric membrane which can be
      actuated (open and closed). When actuated, the chambers confine Cell-Free Protein
      Synthesis (CFPS) reactions expressing a fluorescent protein, allowing for the
      visualization of the reaction kinetics over time using time-lapse fluorescent
      microscopy. Here we demonstrate how this device may be used to measure the noise
      structure of CFPS reactions in a manner that is directly analogous to those used
      to characterize cellular systems, thereby enabling the use of noise biology
      techniques used in cellular systems to characterize CFPS gene circuits and their
      interactions with the cell-free environment. 

PMID- 25867146
TI  - [Prevalence de l'infection a Helicobacter pylori et des lesions endoscopiques
      hautes chez les diabetiques: Etude cas/temoins].
AB  - BACKGROUND: Current data on the prevalence of Helicobacter pylori infection in
      dyspeptic diabetic patients are contradictory in the literature. AIM: the aim was
      to assess the prevalence of Helicobacter pylori infection, gastroscopic lesions,
      and gastric histopathological lesions, in dyspeptic diabetic patients. METHODS:
      It was a case-control study collecting 394 dyspeptic patients (194 diabetic and
      200 nondiabetic patients). RESULTS: The average age of patients was 47 years. 144
      patients (47%) were male and 150 patients (53%) were female. The two patient
      groups were matched for age and sex. The prevalence of Helicobacter pylori
      infection was comparable between the two groups of patients (85% in diabetics
      versus 90% in the controls). The frequency of gastroscopic lesions was 50% in
      diabetics and 55% in controls with no significant difference between the two
      groups. At histology, the prevalence of chronic gastritis, intestinal metaplasia,
      and gastric atrophy was 85%, 13% and 39% respectively in the group of diabetic
      patients. These results were comparable to those found in patients without
      diabetes. CONCLUSION: Our work shows no difference between diabetics and non
      diabetics on the prevalence of Helicobacter pylori infection, gastroscopic, and
      gastric histopathological lesions.

PMID- 25867147
TI  - [Syndrome d'activation macrophagique: une serie de 11 cas tunisiens].
AB  - BACKGROUND: Hemophagocytic syndromes are mostly associated with underlying
      pathology, they can reveal: immunodeficiency, infections, hemopathies, cancers
      and auto-immune diseases. AIM: to investigate clinical, biological features,
      outcome characteristics and underlying pathology of Tunisian patients with
      hemophagocytic syndromes. METHODS: A retrospective study of patients with
      hemophagocytic syndromes admitted in an internal medicine department in Tunis
      over the period 2009-2012. RESULTS: There were 11 patients included, 4 men and
      and 7 women. Mean age was 47,3years. Purpura was observed in 3 cases,
      hepatosplenomegaly in 6 cases and peripheral lymph nodes in 3 cases. Hemorrhagic
      complication was noted in 2 cases. There were an increase of inflammatory indices
      in all the cases. Eight patients had pancytopenia and 3 had bicytopenia. Six
      patients developed intravascular dissiminated coagulation. High levels of
      triglyceridemia was noted in 5 cases and an hyperferritinaemia in all cases.
      Cytological examination of bone marrow confirmed hemophagocytosis in ten cases.
      Hemophagocytosis was associated to infectious diseases in 6 cases, there were 2
      cases of leishmaniasis, septicemia to E.Coli and staphylococcus aureus and lymph
      nodes tuberculosis with HIV. We also noted a case of lymphoma, myelodysplasic
      syndrome, rheumatoid polyarthritis, adult onset still's disease. In one patient,
      the origin of hemophagocytosis remained indefinite. Visceral leishmaniose were
      treated by Glucantime(r), adult Still's disease by corticosteroids and
      methrotrexate(r), lymphoma by chemotherapy. In lymph nodes tuberculosis, there
      were good evolution. Six patients died. CONCLUSION: Hemophagocytic syndrome is a
      rare and life-threatening disease. Pejorative prognosis requires an early therapy
      with etiological treatment.

PMID- 25867148
TI  - [Prevalence et facteurs associes du panique et des troubles phobiques dans les
      structures de premiere ligne].
AB  - BACKGROUND: Panic and phobic disorders are the most common anxiety disorders in
      the general population. They can be a source of suffering, disability and are
      often complicated by other psychiatric disorders. AIMS: To estimate the
      prevalence of panic disorder, agoraphobia, social phobia and specific phobia and
      to assess associated sociodemographic characteristics in primary care patients in
      Sousse governorate. METHODS: A systematic sample of 1246 adults who presented to
      30 different primary care units in Sousse for a medical appointment was recruited
      in a cross- section epidemiological study. The Composite International Diagnostic
      Interview (CIDI 2.1) was used to diagnose the concerned anxiety disorders.
      RESULTS: The lifetime prevalence of panic disorder, agoraphobia, social phobia
      and specific phobia were respectively 1.3%, 2.5%, 6.2% and 24.6%. The female
      gender was significantly predominant in social and specific phobia. The young age
      was found significantly in subjects with social phobia. These anxiety disorders
      were significantly predominant in rural areas, except for social phobia. All of
      these disorders have a chronic course with an index of chronicity ranging from 71
      to 80%. CONCLUSION: Our study provides further evidence of the high prevalence of
      anxiety disorders in primary care and highlights the particular need for general
      physicians to diagnose and treat correctly these disorders.

PMID- 25867149
TI  - A randomized, controlled trial of nebulized 5% hypertonic saline and mixed 5%
      hypertonic saline with epinephrine in bronchiolitis.
AB  - BACKGROUND: Bronchiolitis is a public health problem in the word and in Tunisia.
      Nebulized hypertonic saline seems to have some benefits in bronchiolitis. The aim
      of this study is to evaluate the efficacy of nebulized 5% hypertonic saline alone
      or mixed with epinephrine in bronchiolitis as measured by improvement in clinical
      score, oxygen saturation or reduction in duration of hospitalization. METHODS:
      This prospective, double blind, placebo controlled, randomized clinical trial was
      performed at Children's Hospital of Tunis from February 2012 to Mars 2012. A
      total of 94 patients less than 12 months of age with diagnosis of moderately
      severe bronchiolitis were enrolled and assigned to receive 5% nebulized
      hypertonic saline, mixed 5% hypertonic saline with standard epinephrine 0,1% or
      normal saline (placebo) at admission and every 4 hours during hospitalization.
      RESULTS: There were no significant difference between nebulized 5% hypertonic
      saline, mixed 5% hypertonic saline with epinephrine or normal saline at baseline,
      T30 min, T60 min, and T120 min after start study in Wang severity score, oxygen
      saturation in room air, rate respiratory and heart rate. There was no difference
      in duration of hospitalization. CONCLUSION: Nebulized 5% hypertonic saline or
      mixed 5% hypertonic saline with epinephrine are safety but does not appear
      effective in treating moderately ill infants with the first acute bronchiolitis.

PMID- 25867150
TI  - Primary sarcomatoid lung cancer: clinical and evolutive features: about five
      cases.
AB  - BACKGROUND: Primary sarcomatoid carcinoma of the lung are rare non small cell
      lung cancers (NSCLC) recently individualized by the World Health Organization.
      Their clinical, radiological and evolutive features are not well known but they
      seem to have bad prognosis with rapid progression and early metastases. Although
      they are felt to be chemo-refractory they must be treated as the other subtypes
      of NSCLC. AIM: To evaluate clinical, radiological and evolutive features of
      primary sarcomatoid carcinoma of the lung. METHODS: We report the cases of five
      patients presenting sarcomatoid carcinomas and assess their clinical and
      evolutive data. RESULTS: One patient had stage IIB cancer underwent surgical
      resection and adjuvant chemotherapy, he is alive 18 months later; another had
      stage IIIB was treated by radio and chemotherapy and is alive 6 months later; and
      three other patients had stage IV in whom one had chemotherapy, the two others
      did not because of they had performance status. They died 1 to 3 months after the
      diagnosis. CONCLUSION: Lung sarcomatoid carcinomas are of bad prognosis. Their
      treatment is nowadays not well established. Much more good studies are therefore
      needed.

PMID- 25867151
TI  - [Relation entre la temperature ambiante, l'humidite et la mort subite cardiaque
      au nord de la Tunisie].
AB  - BACKGROUND: Several studies have suggested a relationship between weather
      parameters and the occurrence of sudden cardiac death. AIM: The aim of this work
      was to study the impact of changes in temperature and humidity level on the
      occurrence of sudden cardiac death in the north of Tunisia. METHODS: it's an
      autopsic study that included all victims of sudden cardiac death occurring in
      northern Tunisia between October 2010 and September 2012. The minimum, maximum
      and average of daily temperatures and humidity during the study period were
      recorded and compared with the monthly variation in the occurrence of sudden
      death. RESULTS: The study population included 392 men and 108 women with a mean
      age of 52.2 + / - 15.8 years.The highest rate of sudden death (37%) was observed
      at ambient temperatures below 15 degrees and only 4.2% of deaths occurred at
      temperatures above 30 degrees ambient temperatures (p <0.001). Among the
      population aged over 60 years, the highest mortality rate (47.3%) were recorded
      at temperatures below 15 degrees, while 35.5% of young patients under 40 years
      died during periods with temperatures between 20 and 30 degrees and 56.8% of
      deaths occurred in the humidity levels between 60 and 78% . CONCLUSION: In the
      north of Tunisia where the climate is temperate, a temperature drop below 15
      degrees was significantly associated with a sudden cardiac death. This excess
      winter cardiac mortality was more pronounced in the elderly.

PMID- 25867152
TI  - [Les fistules recto-vaginales d'origine obstetricale: aspects epidemiologiques et
      approaches therapeutiques. Etude multicentrique tunisienne].
AB  - BACKGROUND: Rectovaginal fistulas are abnormal epithelial-lined connections
      between the rectum and vagina. The aquired etiology caused by child birth are
      still frequent in many countries. AIM: to describe epidemiology of obstetrical
      recto vaginal fistula in our country and discuss therapeutic modalities Materiel
      and methods: A retrospective multicentric study among 19 hospital departments
      from February 1982 to January 2007 of obstetrical recto-vaginal fistulas
      including 41 patients. RESULTS: The median diameter of the fistula was 12 mm. the
      treatment consist on excision of the fistula and perineal suturing in 34 cases,
      Advancement flaps was used in four cases, the Musset technique repair in two
      cases, Gracilis transposition for repair was used in one case. Forty five
      patients had satisfactory anatomic and functional satisfactory results. One
      patient had reported dyspareunia. Definitive failure was reported in four cases.
      CONCLUSION: Our study suggests a regression in obstetrical RVF. However many
      efforts on institutional, socioeconomic and obstetrical levels have to be done in
      order to eradicate this pathology. Surgical treatments have good results. However
      prevention of this complication is the best treatment because a major handicap
      for women regarding socioeconomic, functional and psychological effects.

PMID- 25867153
TI  - [Syndrome coronarien aigu sous traitement antiretroviral].
AB  - AIM: The aim of this study is to determine epidemiological, clinical, therapeutic
      and outcome characteristics of acute coronary syndrome in AIDS patients under
      HAART. Results- The charts of 5 patients were reviewed. The mean age, at the time
      of the discovery of HIV infection, was 35 years. Three patients were smokers and
      one had a family history of diabetes and acute coronary syndrome (ACS). Three
      patients received 2 nucleoside reverse transcriptase inhibitors (NRTIs) with
      indinavir. The 2 others received 2 NRTIs with efavirenz with good immunovirologic
      response. Four patients developed mixed dyslipidemia after an average period of
      26 months. Tow patients developed diabetes and one a hypertension. A specific
      treatment was initiated in all cases. These five patients developed an ACS after
      respectively 51, 95, 96,103 and 145 months of ART (median=98 months). ACS
      occurred in 3 patients receiving 2 NRTIs and PI and two others 2 NRTIs with
      efavirenz. The mean age at the onset of ACS was 46 years. One patient underwent a
      triple bypass surgery, tow a stenting of the stenotic coronary and the last 2
      patients received medical treatment with a good clinical outcome. The PI was
      replaced by efavirenz in two patients. Four patients had a recurrence of ACS
      respectively after 2months, 3 months, 12 months, and 62 months after the first
      episode. The five patients are still followed with good clinical and biological
      outcome.

PMID- 25867154
TI  - [Double elargissement annulaire aorto-to-mitral].

PMID- 25867155
TI  - [Ataxie telangiectasia et telangiectasies vesicales].

PMID- 25867156
TI  - [Infarctus segmentaire du grand epiploon].

PMID- 25867157
TI  - Antiphospholipid syndrome and Langerhans cell histiocytosis: an exceptional
      association.

PMID- 25867158
TI  - Small cell carcinoma of the ovary of the hypercalcemia type in children.

PMID- 25867159
TI  - Nephrogenic adenoma of the bladder associated with urinary tuberculosis.

PMID- 25867160
TI  - Colo-colonic intussusception secondary to a colonic lipoma : report of two cases.

PMID- 25867161
TI  - [Adenome hypophysaire thyreotrope].

PMID- 25867162
TI  - Genital fixed drug eruption induced by miconazole with positive provocation test.

PMID- 25867163
TI  - [Le lymphome primitif du sein].

PMID- 25867164
TI  - [Reduction spontanee d'une luxation d'une Prothese totale de hanche associee a
      une Dislocation entre la tete et le col prothetique].

PMID- 25867165
TI  - Exploring factors that influence work analysis data: A meta-analysis of design
      choices, purposes, and organizational context.
AB  - Work analysis is fundamental to designing effective human resource systems. The
      current investigation extends previous research by identifying the differential
      effects of common design decisions, purposes, and organizational contexts on the
      data generated by work analyses. The effects of 19 distinct factors that span
      choices of descriptor, collection method, rating scale, and data source, as well
      as project purpose and organizational features, are explored. Meta-analytic
      results cumulated from 205 articles indicate that many of these variables hold
      significant consequences for work analysis data. Factors pertaining to descriptor
      choice, collection method, rating scale, and the purpose for conducting the work
      analysis each showed strong associations with work analysis data. The source of
      the work analysis information and organizational context in which it was
      conducted displayed fewer relationships. Findings can be used to inform choices
      work analysts make about methodology and postcollection evaluations of work
      analysis information.

PMID- 25867166
TI  - Till stress do us part: On the interplay between perceived stress and
      communication network dynamics.
AB  - This study of perceived stress and communication networks fills 2 theoretical
      gaps in the literature: First, drawing predominantly on conservation of resource
      theory and faultline theory, we demonstrate the role of stress as an "engine of
      action" in network evolution. Second, we extend the stress literature to the
      interpersonal domain by arguing that others' levels of stress influence the
      individual's communication network, and this, in turn, changes his or her stress
      level. At 3 time points, we evaluated the communication ties and perceived stress
      in a unique field setting comprising 115 male participants (in 6 groups)
      performing group-based tasks. We introduce stochastic actor-based models for the
      coevolution of network ties and actor attributes, statistical models that enable
      causal inferences to be drawn regarding the interplay between dynamic networks
      and individual attributes. Using these models, we find that over time,
      individuals experiencing higher levels of perceived stress were less likely to
      create new communication ties and were more likely to maintain existing ties to
      others. Participants also tended to communicate with similarly stressed others.
      Such communication network dynamics further increased individuals' levels of
      perceived stress over time, leading to stress-related vicious cycles. We discuss
      organizational implications that relate to stress and network-related
      interventions.

PMID- 25867167
TI  - What happens before? A field experiment exploring how pay and representation
      differentially shape bias on the pathway into organizations.
AB  - Little is known about how discrimination manifests before individuals formally
      apply to organizations or how it varies within and between organizations. We
      address this knowledge gap through an audit study in academia of over 6,500
      professors at top U.S. universities drawn from 89 disciplines and 259
      institutions. In our experiment, professors were contacted by fictional
      prospective students seeking to discuss research opportunities prior to applying
      to a doctoral program. Names of students were randomly assigned to signal gender
      and race (White, Black, Hispanic, Indian, Chinese), but messages were otherwise
      identical. We hypothesized that discrimination would appear at the informal
      "pathway" preceding entry to academia and would vary by discipline and university
      as a function of faculty representation and pay. We found that when considering
      requests from prospective students seeking mentoring in the future, faculty were
      significantly more responsive to White males than to all other categories of
      students, collectively, particularly in higher-paying disciplines and private
      institutions. Counterintuitively, the representation of women and minorities and
      discrimination were uncorrelated, a finding that suggests greater representation
      cannot be assumed to reduce discrimination. This research highlights the
      importance of studying decisions made before formal entry points into
      organizations and reveals that discrimination is not evenly distributed within
      and between organizations.

PMID- 25867168
TI  - Explaining the black-white gap in cognitive test scores: Toward a theory of
      adverse impact.
AB  - In understanding the causes of adverse impact, a key parameter is the Black-White
      difference in cognitive test scores. To advance theory on why Black-White
      cognitive ability/knowledge test score gaps exist, and on how these gaps develop
      over time, the current article proposes an inductive explanatory model derived
      from past empirical findings. According to this theoretical model, Black-White
      group mean differences in cognitive test scores arise from the following racially
      disparate conditions: family income, maternal education, maternal verbal
      ability/knowledge, learning materials in the home, parenting factors (maternal
      sensitivity, maternal warmth and acceptance, and safe physical environment),
      child birth order, and child birth weight. Results from a 5-wave longitudinal
      growth model estimated on children in the NICHD Study of Early Child Care and
      Youth Development from ages 4 through 15 years show significant Black-White
      cognitive test score gaps throughout early development that did not grow
      significantly over time (i.e., significant intercept differences, but not slope
      differences). Importantly, the racially disparate conditions listed above can
      account for the relation between race and cognitive test scores. We propose a
      parsimonious 3-Step Model that explains how cognitive test score gaps arise, in
      which race relates to maternal disadvantage, which in turn relates to parenting
      factors, which in turn relate to cognitive test scores. This model and results
      offer to fill a need for theory on the etiology of the Black-White ethnic group
      gap in cognitive test scores, and attempt to address a missing link in the theory
      of adverse impact.

PMID- 25867169
TI  - Targeted mesenchymal stem cell and vascular endothelial growth factor strategies
      for repair of nerve defects with nerve tissue implanted autogenous vein graft
      conduits.
AB  - Peripheral nerve gaps exceeding 1 cm require a bridging repair strategy. Clinical
      feasibility of autogenous nerve grafting is limited by donor site comorbidity. In
      this study we investigated neuroregenerative efficacy of autogenous vein grafts
      implanted with tissue fragments from distal nerve in combination with vascular
      endothelial growth factor (VEGF) or mesenchymal stem cells (MSCs) in repair of
      rat peripheral nerve defects. Six-groups of Sprague-Dawley rats (n = 8 each) were
      evaluated in the autogenous setting using a 1.6 cm long peroneal nerve defect:
      Empty vein graft (group 1), Nerve graft (group 2), Vein graft and nerve fragments
      (group 3), Vein graft and nerve fragments and blank microspheres (group 4), Vein
      graft and nerve fragments and VEGF microspheres (group 5), Vein graft and nerve
      fragments and MSCs (group 6). Nerve fragments were derived from distal segment.
      Walking track analysis, electrophysiology and nerve histomorphometry were
      performed for assessment. Peroneal function indices (PFI), electrophysiology
      (amplitude) and axon count results for group 2 were -9.12 +/- 3.07, 12.81 +/-
      2.46 mV, and 1697.88 +/- 166.18, whereas the results for group 5 were -9.35 +/-
      2.55, 12.68 +/- 1.78, and 1566 +/- 131.44, respectively. The assessment results
      did not reveal statistical difference between groups 2 and 5 (P > 0.05). The best
      outcomes were seen in group 2 and 5 followed by group 6. Compared to other
      groups, poorest outcomes were seen in group 1 (P <= 0.05). PFI, electrophysiology
      (amplitude) and axon count results for group 1 were -208.82 +/- 110.69, 0.86 +/-
      0.52, and 444.50 +/- 274.03, respectively. Vein conduits implanted with distal
      nerve-derived nerve fragments improved axonal regeneration. VEGF was superior to
      MSCs in facilitating nerve regeneration. (c) 2015 Wiley Periodicals, Inc.
      Microsurgery 36:578-585, 2016.

PMID- 25867171
TI  - Mechanistic Investigation on the Formation of 2-Halo-3-aryl-4(3H)
      quinazoliniminium Halides from Heteroenyne-allenes: A Computational Study.
AB  - Intramolecular cyclization of the heteroenyne-allene, 2
      ((phenylimino)methyleneamino)-benzonitrile (1) in the presence of HCl to produce
      2-chloro-3-phenyl-4(3H)-quinazoliniminium chloride (Qz) involves the formation of
      two new bonds: a C-Cl bond and a C-N bond. We propose five pathways for this
      reaction. Four of these pathways involve chloride capture to form the C-Cl bond
      prior to the intramolecular nucleophilic attack to form the C-N bond, while one
      pathway involves ring closure to form the C-N bond prior to C-Cl bond formation.
      All calculations were carried out at B3LYP and MP2 levels of theory and employed
      the 6-311G* basis set. The solvent effects were considered using a Polarized
      Continuum Model with dichloromethane as the solvent. The calculations at both
      levels show that the mechanism involves initial protonation of 1, preferentially
      at Nalpha to give 2 which rapidly captures the chloride ion to form 5. This
      intermediate is protonated at the -CN group to form 8ROT, which then tautomerizes
      to its more stable isomer 9ROT. The latter undergoes intramolecular nucleophilic
      attack from Nbeta to the protonated -CN group to form the cyclized intermediate
      12, which tautomerizes to its most stable isomer 13. The coordination of Cl(-)
      ion present in the solution with 13 gives the final product Qz. 

PMID- 25867170
TI  - Quantitative mass spectrometric profiling of cancer-cell proteomes derived from
      liquid and solid tumors.
AB  - In-depth analyses of cancer cell proteomes are needed to elucidate oncogenic
      pathomechanisms, as well as to identify potential drug targets and diagnostic
      biomarkers. However, methods for quantitative proteomic characterization of
      patient-derived tumors and in particular their cellular subpopulations are
      largely lacking. Here we describe an experimental set-up that allows quantitative
      analysis of proteomes of cancer cell subpopulations derived from either liquid or
      solid tumors. This is achieved by combining cellular enrichment strategies with
      quantitative Super-SILAC-based mass spectrometry followed by bioinformatic data
      analysis. To enrich specific cellular subsets, liquid tumors are first
      immunophenotyped by flow cytometry followed by FACS-sorting; for solid tumors,
      laser-capture microdissection is used to purify specific cellular subpopulations.
      In a second step, proteins are extracted from the purified cells and subsequently
      combined with a tumor-specific, SILAC-labeled spike-in standard that enables
      protein quantification. The resulting protein mixture is subjected to either gel
      electrophoresis or Filter Aided Sample Preparation (FASP) followed by tryptic
      digestion. Finally, tryptic peptides are analyzed using a hybrid quadrupole
      orbitrap mass spectrometer, and the data obtained are processed with
      bioinformatic software suites including MaxQuant. By means of the workflow
      presented here, up to 8,000 proteins can be identified and quantified in patient
      derived samples, and the resulting protein expression profiles can be compared
      among patients to identify diagnostic proteomic signatures or potential drug
      targets. 

PMID- 25867172
TI  - The effects of in utero vitamin D deficiency on airway smooth muscle mass and
      lung function.
AB  - We have previously demonstrated increased airway smooth muscle (ASM) mass and
      airway hyperresponsiveness in whole-life vitamin D-deficient female mice. In this
      study, we aimed to uncover the molecular mechanisms contributing to altered lung
      structure and function. RNA was extracted from lung tissue of whole-life vitamin
      D-deficient and -replete female mice, and gene expression patterns were profiled
      by RNA sequencing. The data showed that genes involved in embryonic organ
      development, pattern formation, branching morphogenesis, Wingless/Int signaling,
      and inflammation were differentially expressed in vitamin D-deficient mice.
      Network analysis suggested that differentially expressed genes were connected by
      the hubs matrix metallopeptidase 9; NF-kappa light polypeptide gene enhancer in B
      cells inhibitor, alpha; epidermal growth factor receptor; and E1A binding protein
      p300. Given our findings that developmental pathways may be altered, we
      investigated if the timing of vitamin D exposure (in utero vs. postnatal) had an
      impact on lung health outcomes. Gene expression was measured in in utero or
      postnatal vitamin D-deficient mice, as well as whole-life vitamin D-deficient and
      -replete mice at 8 weeks of age. Baseline lung function, airway
      hyperresponsiveness, and airway inflammation were measured and lungs fixed for
      lung structure assessment using stereological methods and quantification of ASM
      mass. In utero vitamin D deficiency was sufficient to increase ASM mass and
      baseline airway resistance and alter lung structure. There were increased
      neutrophils but decreased lymphocytes in bronchoalveolar lavage. Expression of
      inflammatory molecules S100A9 and S100A8 was mainly increased in postnatal
      vitamin D-deficient mice. These observations suggest that in utero vitamin D
      deficiency can alter lung structure and function and increase inflammation,
      contributing to symptoms in chronic diseases, such as asthma. 

PMID- 25867173
TI  - Highly transparent, conductive, flexible resin films embedded with silver
      nanowires.
AB  - In this article, a low sheet resistance and highly transparent silver nanowire
      (AgNW) resin composite film was demonstrated, which was prepared by a simple and
      efficacious two-step spin-coating method. By burying the AgNWs below the surface
      of the transparent resin matrix which was cured at 150  degrees C in air, we
      achieved a uniform, highly transparent, conductive, flexible film. Compared to
      the reported transparent electrodes, this composite transparent and conductive
      film showed 10 Omega/? sheet resistance and nearly 90% mean optical transmittance
      over the UV-visible range simultaneously. Undergoing hundreds of cycles of
      tensile and compression folding, the composite film slightly increased its sheet
      resistance by less than 5%, displaying good electromechanical flexibility. These
      characteristics of the composite AgNW-resin films were expected to be used in
      applications of flexible optoelectronics. 

PMID- 25867174
TI  - Structural and electronic characterization of multi-electron reduced naphthalene
      (BIAN) cobaloximes.
AB  - Reported here are the syntheses and characterization of cobaloximes that feature
      a bis(imino)acenaphthene (BIAN) appended ligand. The X-ray crystal structures and
      spectroscopy ((1)H NMR or EPR) of the complexes within the series
      [Co(aqdBF2)2(MeCN)2] (), [Co(aqdBF2)(MeCN)2](-) () and [Co(aqdBF2)2(MeCN)2](2-)
      (, ) are reported and the 3-electron reduced complex [Co(aqdBF2)2(MeCN)2](3-) ()
      has been prepared in situ and characterized by (1)H NMR spectroscopy. The X-ray
      crystal structures revealed the presence of a 6-coordinate Co(II) species (), a 5
      coordinate Co(I) species (), and a 4-coordinate complex (, ). In the case of
      complex , evidence from single crystal EPR spectroscopy (g|| = 2.017, g? = 1.987;
      <10 G linewidths) in conjunction with DFT calculations indicate that the EPR
      signal originates from a delocalized ligand-based unpaired spin. The frontier
      orbitals obtained from DFT calculations on , , , & support the electronic
      assignments that were observed spectroscopically. The cathodic cyclic
      voltammogram (CV) of the solvato congener in DMF solution, namely
      [Co(aqdBF2)2(DMF)2], exhibits three reversible redox events near -1.0, -1.5 and 
      2.0 V vs. Fc/Fc(+). Catalytic proton reduction was observed by CV near the third
      redox peak. Compared with other cobaloximes (Ecat = -1.0 V), the delay of
      catalytic onset arises from the existence of a series of resonance-stabilized
      intermediates. 

PMID- 25867175
TI  - Predictors of in vitro fertilization outcomes in women with highest follicle
      stimulating hormone levels >= 12 IU/L: a prospective cohort study.
AB  - OBJECTIVE: The purpose of this study is to evaluate factors predictive of
      outcomes in women with highest follicle-stimulating hormone (FSH) levels >= 12
      IU/L on basal testing, undergoing in vitro fertilization (IVF). METHODS: A
      prospective cohort study was conducted at Stanford University Hospital in the
      Reproductive Endocrinology and Infertility Center for 12 months. Women age 21 to
      43 undergoing IVF with highest FSH levels on baseline testing were included.
      Donor/Recipient and frozen embryo cycles were excluded from this study.
      Prognostic factors evaluated in association with clinical pregnancy rates were
      type of infertility diagnosis and IVF stimulation parameters. RESULTS: The
      current study found that factors associated with clinical pregnancy were:
      increased number of mature follicles on the day of triggering, number of oocytes
      retrieved, number of Metaphase II oocytes if intracytoplasmic sperm injection was
      done, and number of embryos developed 24 hours after retrieval. CONCLUSIONS: Our
      findings suggest that it would be beneficial for women with increased FSH levels
      to attempt a cycle of IVF. Results of ovarian stimulation, especially embryo
      quantity appear to be the best predictors of IVF outcomes and those can only be
      obtained from a cycle of IVF. Therefore, increased basal FSH levels should not
      discourage women from attempting a cycle of IVF.

PMID- 25867176
TI  - Bayesian decision making in human collectives with binary choices.
AB  - Here we focus on the description of the mechanisms behind the process of
      information aggregation and decision making, a basic step to understand emergent
      phenomena in society, such as trends, information spreading or the wisdom of
      crowds. In many situations, agents choose between discrete options. We analyze
      experimental data on binary opinion choices in humans. The data consists of two
      separate experiments in which humans answer questions with a binary response,
      where one is correct and the other is incorrect. The questions are answered
      without and with information on the answers of some previous participants. We
      find that a Bayesian approach captures the probability of choosing one of the
      answers. The influence of peers is uncorrelated with the difficulty of the
      question. The data is inconsistent with Weber's law, which states that the
      probability of choosing an option depends on the proportion of previous answers
      choosing that option and not on the total number of those answers. Last, the
      present Bayesian model fits reasonably well to the data as compared to some other
      previously proposed functions although the latter sometime perform slightly
      better than the Bayesian model. The asset of the present model is the simplicity
      and mechanistic explanation of the behavior. 

PMID- 25867177
TI  - RUNX1/ETO blocks selectin-mediated adhesion via epigenetic silencing of PSGL-1.
AB  - RUNX1/ETO (RE), the t(8;21)-derived leukemic transcription factor associated with
      acute myeloid leukemia (AML) development, deregulates genes involved in
      differentiation, self-renewal and proliferation. In addition, these cells show
      differences in cellular adhesion behavior whose molecular basis is not well
      understood. Here, we demonstrate that RE epigenetically silences the gene
      encoding P-Selectin Glycoprotein Ligand-1 (PSGL-1) and downregulates PSGL-1
      expression in human CD34+ and murine lin- hematopoietic progenitor cells. Levels
      of PSGL-1 inversely and dose-dependently correlate with RE oncogene levels.
      However, a DNA-binding defective mutant fails to downregulate PSGL-1. We show by
      ChIP experiments that the PSGL-1 promoter is a direct target of RE and binding is
      accompanied by high levels of the repressive chromatin mark histone H3K27me3. In
      t(8;21)+ Kasumi-1 cells, PSGL-1 expression is completely restored at both the
      mRNA and cell surface protein levels following RE downregulation with short
      hairpin RNA (shRNA) or RE inhibition with tetramerization-blocking peptides, and
      at the promoter H3K27me3 is replaced by the activating chromatin mark H3K9ac as
      well as by RNA polymerase II. Upregulation of PSGL-1 restores the binding of
      cells to P- and E-selectin and re-establishes myeloid-specific cellular adhesion
      while it fails to bind to lymphocyte-specific L-selectin. Overall, our data
      suggest that the RE oncoprotein epigenetically represses PSGL-1 via binding to
      its promoter region and thus affects the adhesive behavior of t(8;21)+ AML cells.

PMID- 25867178
TI  - Natural and Synthetic Materials for Self-Renewal, Long-Term Maintenance, and
      Differentiation of Induced Pluripotent Stem Cells.
AB  - Induced pluripotent stem cells (iPSCs) have attracted considerable attention from
      the public, clinicians, and scientists since their discovery in 2006, and raised
      huge expectations for regenerative medicine. One of the distinctive features of
      iPSCs is their propensity to differentiate into the cells of three germ lines in
      vitro and in vivo. The human iPSCs can be used to study the mechanisms underlying
      a disease and to monitor the disease progression, for testing drugs in vitro, and
      for cell therapy, avoiding many ethical and immunologic concerns. This technology
      offers the potential to take an individual approach to each patient and allows a
      more accurate diagnosis and specific treatment. However, there are several
      obstacles that impede the use of iPSCs. The derivation of fully reprogrammed
      iPSCs is expensive, time-consuming, and demands meticulous attention to many
      details. The use of biomaterials could increase the efficacy and safety while
      decreasing the cost of tissue engineering. The choice of a substrate utilized for
      iPSC culture is also important because cell-substrate contacts influence cellular
      behavior such as self-renewal, expansion, and differentiation. This Progress
      Report aims to summarize the advantages and drawbacks of natural and synthetic
      biomaterials, and to evaluate their role for maintenance and differentiation of
      iPSCs. 

PMID- 25867179
TI  - Later emotional and behavioral problems associated with sleep problems in
      toddlers: a longitudinal study.
AB  - IMPORTANCE: Childhood sleep problems have been linked to a range of adverse
      health outcomes, but there is limited knowledge as to the temporal association
      between sleep problems and subsequent emotional and behavioral problems in young
      children. OBJECTIVE: To examine whether sleep problems in toddlers aged 18 months
      are related to both concurrent and subsequent emotional and behavioral problems
      in preschool children aged 5 years. DESIGN, SETTING, AND PARTICIPANTS: A large
      population-based longitudinal study was conducted in September 2014 using data
      from the Norwegian Mother and Child Cohort Study conducted at the Norwegian
      Institute of Public Health from June 1, 1999, to December 31, 2008. A total of 32
      662 children or pregnancies were included. EXPOSURES: Sleep was assessed by
      mother-reported child sleep duration and nocturnal awakenings. MAIN OUTCOMES AND
      MEASURES: Emotional and behavioral problems were measured with items from the
      Child Behavior Checklist and operationalized according to recommended clinical
      cutoffs, corresponding to T scores of greater than 65 (93rd percentile). Risk
      ratios (RRs) were calculated using negative binomial regression, controlling for
      emotional and behavioral problems at 18 months and other relevant covariates.
      RESULTS: Short sleep duration (<=10 hours) in 556 children (1.7%) and frequent
      nocturnal awakenings (>=3 times) in 1033 children (3.2%) at 18 months
      significantly predicted both concurrent and later incidence of emotional and
      behavioral problems at 5 years. The longitudinal RRs were generally larger for
      internalizing problems, with adjusted RRs of 1.59 (95% CI, 1.23-2.08) for both
      short sleep duration and 1.57 (95% CI, 1.28-1.93) for nocturnal awakenings; RRs
      for externalizing problems were 1.77 (95% CI, 1.37-2.30) and 1.25 (95% CI, 1.00
      1.58), respectively. Additional adjustment for emotional and behavioral problems
      at 18 months slightly reduced the strength of these associations, and all RRs
      remained significant in the fully adjusted models. CONCLUSIONS AND RELEVANCE:
      Early sleep problems predict later development of emotional and behavioral
      problems. Intervention studies are needed to examine whether sleep programs
      targeting early childhood may avert the onset of later adverse outcomes.

PMID- 25867180
TI  - Hospital and regional variation in Medicare payment for inpatient episodes of
      care.

PMID- 25867181
TI  - Milk fat globule-EGF factor VIII attenuates CNS injury by promoting neural stem
      cell proliferation and migration after cerebral ischemia.
AB  - The mediators in activating neural stem cells during the regenerative process of
      neurogenesis following stroke have not been fully identified. Milk fat globule
      EGF Factor VIII (MFG-E8), a secreted glycoprotein serves several cellular
      functions by binding to its receptor, alphav beta3-integrin. However, its role in
      regulating neural stem cells after stroke has not been determined yet. We
      therefore, aim to reveal whether MFG-E8 promotes neural stem cell proliferation
      and migration during stroke. Stroke was induced in wild-type (Wt) and MFG-E8
      deficinet (Mfge8-/-) mice by transient middle cerebral artery occlusion (tMCAO).
      Commercially available recombinant mouse MFG-E8 (rmMFG-E8) was used for
      mechanistic assays in neural stem cell line, while the in house prepared
      recombinant human MFG-E8 (rhMFG-E8) was used for in vivo administration into rats
      with tMCAO. The in vitro effects of recombinant rmMFG-E8 for the neural stem cell
      proliferation and migration were determined by BrdU and transwell migration
      assay, respectively. The expression of cyclin D2, p53 and netrin-1, was analyzed
      by qPCR. We report that the treatment of rhMFG-E8 significantly improved the
      neurological deficit score, body weight lost and neural stem cell proliferation
      in a rat model of tMCAO. Conversely, decreased neural stem cell proliferation was
      observed in Mfge8-/- mice in comparison with the Wt counterparts underwent tMCAO.
      rmMFG-E8 stimulated the proliferation of mouse embryonic neural stem cells via
      upregulation of cyclin D2 and downregulation of p53, which is mediated by alphav
      beta3-integrin. rmMFG-E8 also promoted mouse embryonic neural stem cell migration
      via alphav beta3-integrin dependent manner in upregulating netrin-1. Our findings
      suggest MFG-E8 to promote neural stem cell proliferation and migration, which
      therefore establishes a promising therapeutic strategy for cerebral ischemia. 

PMID- 25867183
TI  - Surface Eroding, Semicrystalline Polyanhydrides via Thiol-Ene "Click"
      Photopolymerization.
AB  - Surface eroding and semicrystalline polyanhydrides, with tunable erosion times
      and drug delivery pharmacokinetics largely dictated by erosion, are produced
      easily with thiol-ene "click" polymerization. This strategy yields both linear
      and cross-linked network polyanhydrides that are readily and fully cured within
      minutes using photoinitiation, can contain up to 60% crystallinity, and have
      tensile moduli up to 25 MPa for the compositions studied. Since they readily
      undergo hydrolysis and exhibit the oft-preferred surface erosion mechanism, they
      may be particularly useful in drug delivery applications. The polyanhydrides were
      degraded under pseudophysiological conditions and cylindrical samples (10 mm
      diameter * 5 mm height) were completely degraded within ~10 days, with the mass
      time profile being linear for much of this time after a ~24 h induction period.
      Drug release studies, using lidocaine as a model, showed pharmacokinetics that
      displayed a muted burst release in the early stages of erosion, but then a
      delayed release profile that is closely correlated to the erosion kinetics.
      Furthermore, cytotoxicity studies of the linear and cross-linked semicrystalline
      polyanhydrides, and degradation products, against fibroblast cells indicate that
      the materials have good cytocompatibility. Overall, cells treated with up to 2500
      mg/L of the semicrystalline polyanhydrides and degradation products show >90%
      human dermal fibroblast adult (HDFa) cell viability indicative of good
      cytocompatibility. 

PMID- 25867184
TI  - Abstracts of the 16th Annual NATA Symposium on Patient Blood Management,
      Haemostasis and Thrombosis, April 16-17, 2015, Prague, Czech Republic.

PMID- 25867182
TI  - Upregulation of Angiotensin (1-7)-Mediated Signaling Preserves Endothelial
      Function Through Reducing Oxidative Stress in Diabetes.
AB  - AIMS: Angiotensin-converting enzyme 2 (ACE2)-angiotensin (1-7) [Ang (1-7)]-Mas
      constitutes the vasoprotective axis and is demonstrated to antagonize the
      vascular pathophysiological effects of the classical renin-angiotensin system. We
      sought to study the hypothesis that upregulation of ACE2-Ang (1-7) signaling
      protects endothelial function through reducing oxidative stress that would result
      in beneficial outcome in diabetes. RESULTS: Ex vivo treatment with Ang (1-7)
      enhanced endothelium-dependent relaxation (EDR) in renal arteries from diabetic
      patients. Both Ang (1-7) infusion via osmotic pump (500 ng/kg/min) for 2 weeks
      and exogenous ACE2 overexpression mediated by adenoviral ACE2 via tail vein
      injection (10(9) pfu/mouse) rescued the impaired EDR and flow-mediated dilatation
      (FMD) in db/db mice. Diminazene aceturate treatment (15 mg/kg/day) activated
      ACE2, increased the circulating Ang (1-7) level, and augmented EDR and FMD in
      db/db mouse arteries. In addition, activation of the ACE2-Ang (1-7) axis reduced
      reactive oxygen species (ROS) overproduction determined by dihydroethidium
      staining, CM-H2DCFDA fluorescence imaging, and chemiluminescence assay in db/db
      mouse aortas and also in high-glucose-treated endothelial cells. Pharmacological
      benefits of ACE2-Ang (1-7) upregulation on endothelial function were confirmed in
      ACE2 knockout (ACE2 KO) mice both ex vivo and in vitro. INNOVATION: We elucidate
      that the ACE2-Ang (1-7)-Mas axis serves as an important signal pathway in
      endothelial cell protection in diabetic mice, especially in diabetic human
      arteries. CONCLUSION: Endogenous ACE2-Ang (1-7) activation or ACE2 overexpression
      preserves endothelial function in diabetic mice through increasing nitric oxide
      bioavailability and inhibiting oxidative stress, suggesting the therapeutic
      potential of ACE2-Ang(1-7) axis activation against diabetic vasculopathy.
      Antioxid.

PMID- 25867185
TI  - A Light-Induced Reaction with Oxygen Leads to Chromophore Decomposition and
      Irreversible Photobleaching in GFP-Type Proteins.
AB  - Photobleaching and photostability of proteins of the green fluorescent protein
      (GFP) family are crucially important for practical applications of these widely
      used biomarkers. On the basis of simulations, we propose a mechanism for
      irreversible bleaching in GFP-type proteins under intense light illumination. The
      key feature of the mechanism is a photoinduced reaction of the chromophore with
      molecular oxygen (O2) inside the protein barrel leading to the chromophore's
      decomposition. Using quantum mechanics/molecular mechanics (QM/MM) modeling we
      show that a model system comprising the protein-bound Chro(-) and O2 can be
      excited to an electronic state of the intermolecular charge-transfer (CT)
      character (Chro(*)...O2(-*)). Once in the CT state, the system undergoes a series
      of chemical reactions with low activation barriers resulting in the cleavage of
      the bridging bond between the phenolic and imidazolinone rings and disintegration
      of the chromophore. 

PMID- 25867186
TI  - Ganzfeld stimulation or sleep enhance long term motor memory consolidation
      compared to normal viewing in saccadic adaptation paradigm.
AB  - Adaptation of saccade amplitude in response to intra-saccadic target displacement
      is a type of implicit motor learning which is required to compensate for
      physiological changes in saccade performance. Once established trials without
      intra-saccadic target displacement lead to de-adaptation or extinction, which has
      been attributed either to extra-retinal mechanisms of spatial constancy or to the
      influence of the stable visual surroundings. Therefore we investigated whether
      visual deprivation ("Ganzfeld"-stimulation or sleep) can partially maintain this
      motor learning compared to free viewing of the natural surroundings. Thirty-five
      healthy volunteers performed two adaptation blocks of 100 inward adaptation
      trials - interspersed by an extinction block - which were followed by a two-hour
      break with or without visual deprivation (VD). Using additional adaptation and
      extinction blocks short and long (4 weeks) term memory of this implicit motor
      learning were tested. In the short term, motor memory tested immediately after
      free viewing was superior to adaptation performance after VD. In the long run,
      however, effects were opposite: motor memory and relearning of adaptation was
      superior in the VD conditions. This could imply independent mechanisms that
      underlie the short-term ability of retrieving learned saccadic gain and its long
      term consolidation. We suggest that subjects mainly rely on visual cues (i.e.,
      retinal error) in the free viewing condition which makes them prone to changes of
      the visual stimulus in the extinction block. This indicates the role of a stable
      visual array for resetting adapted saccade amplitudes. In contrast, visual
      deprivation (GS and sleep), might train subjects to rely on extra-retinal cues,
      e.g., efference copy or prediction to remap their internal representations of
      saccade targets, thus leading to better consolidation of saccadic adaptation. 

PMID- 25867188
TI  - Solution-phase self-assembly of complementary halogen bonding polymers.
AB  - Noncovalent halogen bonding interactions are explored as a driving force for
      solution phase macromolecular self-assembly. Conditions for controlled radical
      polymerization of an iodoperfluoroarene-bearing methacrylate halogen bond donor
      were identified. An increase in association constant relative to monomeric
      species was observed for the interaction between halogen bond donor and acceptor
      polymers in solution. When the polymeric donor was combined with a block
      copolymer bearing halogen bond-accepting amine groups, higher-order structures
      were obtained in both organic solvent and in water. Transmission electron
      microscopy, dynamic light scattering and nuclear magnetic resonance spectroscopic
      data are consistent with structures having cores composed of the interacting
      halogen bond donor and acceptor segments. 

PMID- 25867187
TI  - A murine model of arterial restenosis: technical aspects of femoral wire injury.
AB  - Cardiovascular disease caused by atherosclerosis is the leading cause of death in
      the developed world. Narrowing of the vessel lumen, due to atherosclerotic plaque
      development or the rupturing of established plaques, interrupts normal blood flow
      leading to various morbidities such as myocardial infarction and stroke. In the
      clinic endovascular procedures such as angioplasty are commonly performed to
      reopen the lumen. However, these treatments inevitably damage the vessel wall as
      well as the vascular endothelium, triggering an excessive healing response and
      the development of a neointimal plaque that extends into the lumen causing vessel
      restenosis (re-narrowing). Restenosis remains a major cause of failure of
      endovascular treatments for atherosclerosis. Thus, preclinical animal models of
      restenosis are vitally important for investigating the pathophysiological
      mechanisms as well as translational approaches to vascular interventions. Among
      several murine experimental models, femoral artery wire injury is widely accepted
      as the most suitable for studies of post-angioplasty restenosis because it
      closely resembles the angioplasty procedure that injures both endothelium and
      vessel wall. However, many researchers have difficulty utilizing this model due
      to its high degree of technical difficulty. This is primarily because a metal
      wire needs to be inserted into the femoral artery, which is approximately three
      times thinner than the wire, to generate sufficient injury to induce prominent
      neointima. Here, we describe the essential surgical details to effectively
      overcome the major technical difficulties of this model. By following the
      presented procedures, performing the mouse femoral artery wire injury becomes
      easier. Once familiarized, the whole procedure can be completed within 20 min. 

PMID- 25867189
TI  - T346Hunter: a novel web-based tool for the prediction of type III, type IV and
      type VI secretion systems in bacterial genomes.
AB  - T346Hunter (Type Three, Four and Six secretion system Hunter) is a web-based tool
      for the identification and localisation of type III, type IV and type VI
      secretion systems (T3SS, T4SS and T6SS, respectively) clusters in bacterial
      genomes. Non-flagellar T3SS (NF-T3SS) and T6SS are complex molecular machines
      that deliver effector proteins from bacterial cells into the environment or into
      other eukaryotic or prokaryotic cells, with significant implications for
      pathogenesis of the strains encoding them. Meanwhile, T4SS is a more functionally
      diverse system, which is involved in not only effector translocation but also
      conjugation and DNA uptake/release. Development of control strategies against
      bacterial-mediated diseases requires genomic identification of the virulence
      arsenal of pathogenic bacteria, with T3SS, T4SS and T6SS being major determinants
      in this regard. Therefore, computational methods for systematic identification of
      these specialised machines are of particular interest. With the aim of
      facilitating this task, T346Hunter provides a user-friendly web-based tool for
      the prediction of T3SS, T4SS and T6SS clusters in newly sequenced bacterial
      genomes. After inspection of the available scientific literature, we constructed
      a database of hidden Markov model (HMM) protein profiles and sequences
      representing the various components of T3SS, T4SS and T6SS. T346Hunter performs
      searches of such a database against user-supplied bacterial sequences and
      localises enriched regions in any of these three types of secretion systems.
      Moreover, through the T346Hunter server, users can visualise the predicted
      clusters obtained for approximately 1700 bacterial chromosomes and plasmids.
      T346Hunter offers great help to researchers in advancing their understanding of
      the biological mechanisms in which these sophisticated molecular machines are
      involved. T346Hunter is freely available at http://bacterial-virulence
      factors.cbgp.upm.es/T346Hunter. 

PMID- 25867192
TI  - Positioning artifact causing retained foreign object appearance in a radiograph
      of a venous catheter.
AB  - In preparation for an abdominal tumor debulking procedure, a patient had a right
      internal jugular central venous catheter (CVC) inserted. A radiologist
      interpreted a postoperative chest radiograph as containing a 7-cm foreign body in
      the distal lumen of the CVC. After removal, dissection of the CVC revealed a
      polyurethane plug in the distal lumen. The manufacturer (Arrow(r)) states that
      the synthetic plug is part of standard CVC construction that may produce a
      radiopaque signal with specific patient positioning during radiography. This
      report is intended to raise awareness of the potential for this radiographic
      finding and prevent the unnecessary removal of clinically indicated CVCs. 

PMID- 25867193
TI  - Venous gas embolism caused by fibrin sealant application to the prostate during
      greenlight laser photoselective vaporization.
AB  - Venous gas embolism is a complication of fibrin sealant application and is a well
      described event during various modes of prostate resection. We describe the case
      of a nitrogen venous gas embolism during Greenlight laser photovaporization of
      the prostate during the application of fibrin sealant to the operative site for
      hemostasis. Fibrin sealant application by a compressed gas applicator is a cause
      of venous air embolism, and this case highlights the need to keep venous gas
      embolism in mind when compressed gas applicators are used. 

PMID- 25867194
TI  - Anesthetic management of a parturient with hyperekplexia.
AB  - Hyperekplexia is a hereditary disorder characterized by exaggerated startle
      reflex in response to unexpected acoustic, tactile, and other stimuli. Neonates
      with hyperekplexia may present with hypertonia, developmental delays, apnea, and
      sudden death. The diagnosis is based on published clinical criteria. In some
      cases, a mutation encoding the postsynaptic inhibitory glycine receptors (GLRA1,
      GLRB) or presynaptic glycine transporter (SLC6A5) resulting in abnormal
      glycinergic neurotransmission is present. We report the case of a 38-year-old
      gravida 6 para 1 (G6P1) parturient with hyperekplexia who underwent successful
      vaginal delivery managed by the anesthesiology and neonatology service teams from
      initial antenatal consultation to labor and delivery to hospital discharge. 

PMID- 25867195
TI  - Sonographically guided superior laryngeal nerve block during awake fiberoptic
      intubation.
AB  - We report 5 patients who underwent ultrasound-guided superior laryngeal nerve
      block before awake intubation and general anesthesia. We used a 8- to 15-MHz
      hockey stick-shaped ultrasound transducer (HST15-8/20 linear probe, Ultrasonix)
      to visualize the superior laryngeal nerve. A 3.8-cm 25-G needle was inserted in
      real time and directed toward the superior laryngeal nerve followed by
      circumferential placement of local anesthetic. All 5 patients tolerated
      subsequent awake fiberoptic intubation with either minimal or no sedation.
      Sonographically guided superior laryngeal nerve block may be useful in patients
      where identification of landmarks in the neck is difficult as a result of patient
      anatomy. 

PMID- 25867196
TI  - Biomechanical patterns of text-message distraction.
AB  - The objective of this study was to identify biomechanical measures that can
      distinguish texting distraction in a laboratory-simulated driving environment.
      The goal would be to use this information to provide an intervention for risky
      driving behaviour. Sixteen subjects participated in this study. Three independent
      variables were tested: task (texting, visual targeting, weighted and non-weighted
      movements), task direction (front and side) and task distance (close and far).
      Dependent variables consisted of biomechanical moments, head displacement and the
      length of time to complete each task. Results revealed that the time to complete
      each task was higher for texting compared to other tasks. Peak moments during
      texting were only distinguishable from visual targeting. Peak head displacement
      and cumulative biomechanical exposure measures indicated that texting can be
      distinguished from other tasks. Therefore, it may be useful to take into account
      both temporal and biomechanical measures when considering warning systems to
      detect texting distraction. 

PMID- 25867197
TI  - Mesenchymal Stem Cell Exosomes Induce Proliferation and Migration of Normal and
      Chronic Wound Fibroblasts, and Enhance Angiogenesis In Vitro.
AB  - Although chronic wounds are common and continue to be a major cause of morbidity
      and mortality, treatments for these conditions are lacking and often ineffective.
      A large body of evidence exists demonstrating the therapeutic potential of
      mesenchymal stem cells (MSCs) for repair and regeneration of damaged tissue,
      including acceleration of cutaneous wound healing. However, the exact mechanisms
      of wound healing mediated by MSCs are unclear. In this study, we examined the
      role of MSC exosomes in wound healing. We found that MSC exosomes ranged from 30
      to 100-nm in diameter and internalization of MSC exosomes resulted in a dose
      dependent enhancement of proliferation and migration of fibroblasts derived from
      normal donors and chronic wound patients. Uptake of MSC exosomes by human
      umbilical vein endothelial cells also resulted in dose-dependent increases of
      tube formation by endothelial cells. MSC exosomes were found to activate several
      signaling pathways important in wound healing (Akt, ERK, and STAT3) and induce
      the expression of a number of growth factors [hepatocyte growth factor (HGF),
      insulin-like growth factor-1 (IGF1), nerve growth factor (NGF), and stromal
      derived growth factor-1 (SDF1)]. These findings represent a promising opportunity
      to gain insight into how MSCs may mediate wound healing. 

PMID- 25867198
TI  - Relationship between the concentrations of heavy metals and bioelements in aging
      men with metabolic syndrome.
AB  - Heavy metals may exacerbate metabolic syndrome (MS) but abnormal serum
      concentrations of bioelements may also co-exist with MS. The primary aim of the
      study was to assess the relationship of blood heavy metal and bioelement
      concentrations and MS, in men aged 50-75 years. Heavy metals-lead (Pb), cadmium
      (Cd), mercury (Hg), arsenic (As), tungsten (W), Macroelements-magnesium (Mg) and
      calcium (Ca), and microelements-iron (Fe), zinc (Zn) copper (Cu), chromium (Cr),
      molybdenum (Mo), selenium (Se) and manganese (Mn), body mass index (BMI), waist
      to hip ratio (WHR), abdominal circumference (AC) and blood pressure (BP), total
      cholesterol (TCh), high-density lipoprotein (HDL), low-density lipoprotein (LDL),
      triglyceride (TG), fasting plasma glucose (FPG), insulin, and Homeostasis Model
      Assessment-Insulin resistance (HOMA-IR). The men with MS showed statistically
      significant higher Zn and lower Mg concentrations. Those with diabetes had higher
      Ca concentration and lower Mg concentration. Cr and Mn concentrations were
      significantly higher in obese men. The participants with hypertension had lower
      Mg concentration. We found statistically significant positive correlations (W
      TCh, W-LDL, Mg-TCh, Mg-LDL, Ca-TCh, Ca-LDL, Ca-insulin, Ca-HOMAR-IR, Zn-TG, Zn
      insulin, Zn-HOMA-IR, Cu-BP systolic, Mn-BMI, Mn-AC, Mn-WHR, Mn-insulin, Mn-HOMA
      IR, Se-TCh, Se-LDL, Se-TG, Se-insulin, Se-HOMA-IR, Cr-TCh, Cr-HDL, Cr-LDL, Cr-TG)
      and negative correlations (Cd-insulin, Hg-WHR, W-insulin, W-HOMA-IR, Mg-BMI, Mg
      AC, Mg-WHR, Mg-BP systolic, Mo-insulin, Mn-HDL). Tungsten may contribute to lipid
      disorders. Magnesium appears to play the protective role in the occurrence of
      metabolic disorders. Microelements Mn, Cr and Se may intensify MS. 

PMID- 25867199
TI  - Exposure to seasonal temperatures during the last month of gestation and the risk
      of preterm birth in Stockholm.
AB  - Recent evidence from studies performed mainly in warm climates suggests an
      association between exposure to extreme temperatures late in pregnancy and an
      increased risk of preterm delivery. However, there have been fewer studies on the
      effect of low temperatures. The aim of this study is to explore the potential
      association between both heat and cold during late pregnancy and an increased
      risk of preterm birth in the northern location of Stockholm, Sweden. All
      singleton spontaneous births that took place in greater Stockholm (1998-2006)
      were included. Non-linear and delayed effects of mean temperature on the risk of
      preterm birth were explored through distributed lag non-linear models. Extreme
      and moderate heat and cold were estimated separately through quasi-Poisson
      regression analysis in two seasonal periods (heat in warm season, cold in cold
      season). The risk of preterm birth increased by 4%-5% when the mean temperature
      reached the 75th percentile (moderate heat) four weeks earlier (reference: the
      annual median value), with a maximum cumulative risk ratio of 2.50 (95%
      confidence interval: 1.02-6.15). Inconsistent associations were obtained for cold
      and extreme heat. Exposure to moderately high temperatures during late pregnancy
      might be associated with an increase in risk of preterm birth in Stockholm. 

PMID- 25867200
TI  - Probing and controlling liquid crystal helical nanofilaments.
AB  - We report the first in situ measurement of the helical pitch of the helical
      nanofilament B4 phase of bent-core liquid crystals using linearly polarized,
      resonant soft X-ray scattering at the carbon K-edge. A strong, anisotropic
      scattering peak corresponding to the half-pitch of the twisted smectic layer
      structure was observed. The equilibrium helical half-pitch of NOBOW is found to
      be 120 nm, essentially independent of temperature. However, the helical pitch can
      be tuned by mixing guest organic molecules with the bent-core host, followed by
      thermal annealing. 

PMID- 25867202
TI  - In vivo assessment of rodent Plasmodium parasitemia and merozoite invasion by
      flow cytometry.
AB  - During blood stage infection, malaria parasites invade, mature, and replicate
      within red blood cells (RBCs). This results in a regular growth cycle and an
      exponential increase in the proportion of malaria infected RBCs, known as
      parasitemia. We describe a flow cytometry based protocol which utilizes a
      combination of the DNA dye Hoechst, and the mitochondrial membrane potential dye,
      JC-1, to identify RBCs which contain parasites and therefore the parasitemia, of
      in vivo blood samples from Plasmodium chabaudi adami DS infected mice. Using this
      approach, in combination with fluorescently conjugated antibodies, parasitized
      RBCs can be distinguished from leukocytes, RBC progenitors, and RBCs containing
      Howell-Jolly bodies (HJ-RBCs), with a limit of detection of 0.007% parasitemia.
      Additionally, we outline a method for the comparative assessment of merozoite
      invasion into two different RBC populations. In this assay RBCs, labeled with two
      distinct compounds identifiable by flow cytometry, are transfused into infected
      mice. The relative rate of invasion into the two populations can then be assessed
      by flow cytometry based on the proportion of parasitized RBCs in each population
      over time. This combined approach allows the accurate measurement of both
      parasitemia and merozoite invasion in an in vivo model of malaria infection. 

PMID- 25867201
TI  - Three dimensional liquid chromatography coupling ion exchange
      chromatography/hydrophobic interaction chromatography/reverse phase
      chromatography for effective protein separation in top-down proteomics.
AB  - To address the complexity of the proteome in mass spectrometry (MS)-based top
      down proteomics, multidimensional liquid chromatography (MDLC) strategies that
      can effectively separate proteins with high resolution and automation are highly
      desirable. Although various MDLC methods that can effectively separate peptides
      from protein digests exist, very few MDLC strategies, primarily consisting of
      2DLC, are available for intact protein separation, which is insufficient to
      address the complexity of the proteome. We recently demonstrated that hydrophobic
      interaction chromatography (HIC) utilizing a MS-compatible salt can provide high
      resolution separation of intact proteins for top-down proteomics. Herein, we have
      developed a novel 3DLC strategy by coupling HIC with ion exchange chromatography
      (IEC) and reverse phase chromatography (RPC) for intact protein separation. We
      demonstrated that a 3D (IEC-HIC-RPC) approach greatly outperformed the
      conventional 2D IEC-RPC approach. For the same IEC fraction (out of 35 fractions)
      from a crude HEK 293 cell lysate, a total of 640 proteins were identified in the
      3D approach (corresponding to 201 nonredundant proteins) as compared to 47 in the
      2D approach, whereas simply prolonging the gradients in RPC in the 2D approach
      only led to minimal improvement in protein separation and identifications.
      Therefore, this novel 3DLC method has great potential for effective separation of
      intact proteins to achieve deep proteome coverage in top-down proteomics. 

PMID- 25867203
TI  - Surgical technique for the implantation of tissue engineered vascular grafts and
      subsequent in vivo monitoring.
AB  - The development of Tissue Engineered Vessels (TEVs) is advanced by the ability to
      routinely and effectively implant TEVs (4-5 mm in diameter) into a large animal
      model. A step by-step protocol for inter-positional placement of the TEV and real
      time digital assessment of the TEV and native carotid arteries is described here.
      In vivo monitoring is made possible by the implantation of flow probes, catheters
      and ultrasonic crystals (capable of recording dynamic diameter changes of
      implanted TEVs and native carotid arteries) at the time of surgery. Once
      implanted, researchers can calculate arterial blood flow patterns, invasive blood
      pressure and artery diameter yielding parameters such as pulse wave velocity,
      augmentation index, pulse pressures and compliance. Data acquisition is
      accomplished using a single computer program for analysis throughout the duration
      of the experiment. Such invaluable data provides insight into TEV matrix
      remodeling, its resemblance to native/sham controls and overall TEV performance
      in vivo. 

PMID- 25867204
TI  - Hemolytic events after the administration of lyophilized versus liquid immune
      globulin: an analysis of a single manufacturer's safety database.
AB  - BACKGROUND: Recent publications have raised concerns that liquid immune globulins
      (IGs) may be associated with either a higher or a lower frequency of hemolytic
      events compared to lyophilized IGs, among other reasons due to the differences of
      their isohemagglutinin content. The aim of this study was to evaluate the
      relationship of hemolytic events to product presentation (liquid versus
      lyophilized) and to examine the relationship between total IG doses administered
      and the individual isohemagglutinin titers of IG lots infused. STUDY DESIGN AND
      METHODS: The reporting rate as well as the proportional reporting rate (PRR) of
      hemolytic events for liquid (Gammagard liquid [GGL]) and lyophilized IG
      (Gammagard S/D [GGSD]) received spontaneously from the United States was
      calculated. For all hemolytic events received spontaneously from global sources,
      total IG doses (g/kg body weight) and the loading dose of isohemagglutinins
      (total IG dose infused * isohemagglutinin titers of infused lots) were
      determined. RESULTS: With 0.27 and 0.33 cases per 1 million grams distributed,
      the reporting rates for GGL and GGSD are comparable, further confirmed by a PRR
      of 1.0 (95% confidence interval, 0.4-2.7). Hemolytic events for GGL and GGSD were
      observed with low loading doses of isohemagglutinins, and lots with high
      isohemagglutinin titers did not contribute to the development of hemolytic events
      in a higher proportion than lots with low titers CONCLUSIONS: Hemolysis
      associated with GGL or GGSD can occur even with low loading doses of
      isohemagglutinins. Data presented do not indicate that high isohemagglutinin
      titers of IG products play a major role in the development of these events.

PMID- 25867205
TI  - Electrochemical characterization of electrospun nanocomposite polymer blend
      electrolyte fibrous membrane for lithium battery.
AB  - Novel hybrid (organic/inorganic) electrospun nanocomposite polymer blend
      electrolyte fibrous membranes with the composition poly(vinylidene difluoride-co
      hexafluoropropylene) [P(VdF-co-HFP)]/poly(methyl methacrylate) [P(MMA)]/magnesium
      aluminate (MgAl2O4)/LiPF6 were prepared by the electrospinning technique. All of
      the prepared electrospun P(VdF-co-HFP), PMMA blend [90% P(VdF-co-HFP)/10% PMMA],
      and nanocomposite polymer blend [90% P(VdF-co-HFP)/10% PMMA/x wt % MgAl2O4 (x =
      2, 4, 6, and 8)] fibrous membranes were characterized by X-ray diffraction,
      Fourier transform infrared spectroscopy, differential scanning calorimetry, and
      scanning electron microscopy. The fibrous nanocomposite separator-cum-polymer
      blend electrolyte membranes were obtained by soaking the nanocomposite polymer
      blend membranes in an electrolyte solution containing 1 M LiPF6 in ethylene
      carbonate (EC)/diethyl carbonate (DEC) (1:1, v/v). The newly developed fibrous
      nanocomposite polymer blend electrolyte [90% P(VdF-co-HFP)/10% PMMA/6 wt %
      MgAl2O4/LiPF6] membrane showed a low crystallinity, low average fiber diameter,
      high thermal stability, high electrolyte uptake, high conductivity (2.60 * 10(-3)
      S cm(-1)) at room temperature, and good potential stability above 4.5 V. The best
      properties of the fibrous nanocomposite polymer blend electrolyte (NCPBE)
      membrane with a 6 wt % MgAl2O4 filler content was used for the fabrication of a
      Li/NCPBE/LiCoO2 CR 2032 coin cell. The electrochemical performance of the
      fabricated CR 2032 cell was evaluated at a current density of 0.1 C-rate. The
      fabricated CR 2032 cell lithium battery using the newly developed NCPBE membrane
      delivered an initial discharge capacity of 166 mAh g(-1) and a stable cycle
      performance. 

PMID- 25867207
TI  - Zero valent iron simultaneously enhances methane production and sulfate reduction
      in anaerobic granular sludge reactors.
AB  - Zero valent iron (ZVI) packed anaerobic granular sludge reactors have been
      developed for improved anaerobic wastewater treatment. In this work, a
      mathematical model is developed to describe the enhanced methane production and
      sulfate reduction in anaerobic granular sludge reactors with the addition of ZVI.
      The model is successfully calibrated and validated using long-term experimental
      data sets from two independent ZVI-enhanced anaerobic granular sludge reactors
      with different operational conditions. The model satisfactorily describes the
      chemical oxygen demand (COD) removal, sulfate reduction and methane production
      data from both systems. Results show ZVI directly promotes propionate degradation
      and methanogenesis to enhance methane production. Simultaneously, ZVI alleviates
      the inhibition of un-dissociated H2S on acetogens, methanogens and sulfate
      reducing bacteria (SRB) through buffering pH (Fe(0) + 2H(+) = Fe(2+) + H2) and
      iron sulfide precipitation, which improve the sulfate reduction capacity,
      especially under deterioration conditions. In addition, the enhancement of ZVI on
      methane production and sulfate reduction occurs mainly at relatively low COD/
      [Formula: see text] ratio (e.g., 2-4.5) rather than high COD/ [Formula: see text]
      ratio (e.g., 16.7) compared to the reactor without ZVI addition. The model
      proposed in this work is expected to provide support for further development of a
      more efficient ZVI-based anaerobic granular system. 

PMID- 25867206
TI  - Characterization of endolymphatic sac tumors and von Hippel-Lindau disease in the
      International Endolymphatic Sac Tumor Registry.
AB  - BACKGROUND: Endolymphatic sac tumors (ELSTs) are, with a prevalence of up to 16%,
      a component of von Hippel-Lindau (VHL) disease. Data from international
      registries regarding heritable fraction and characteristics, germline VHL
      mutation frequency, and prevalence are lacking. METHODS: Systematic registration
      of ELSTs from international centers of otorhinolaryngology and from
      multidisciplinary VHL centers' registries was performed. Molecular genetic
      analyses of the VHL gene were offered to all patients. RESULTS: Our population
      based registry comprised 93 patients with ELST and 1789 patients with VHL. The
      prevalence of VHL germline mutations in apparently sporadic ELSTs was 39%. The
      prevalence of ELSTs in patients with VHL was 3.6%. ELST was the initial
      manifestation in 32% of patients with VHL-ELST. CONCLUSION: Prevalence of ELST in
      VHL disease is much lower compared to the literature. VHL-associated ELSTs can be
      the first presentation of the syndrome and mimic sporadic tumors, thus
      emphasizing the need of molecular testing in all presentations of ELST. (c) 2015
      Wiley Periodicals, Inc. Head Neck 38: 673-679, 2016.

PMID- 25867208
TI  - Variables related to working capability among Swiss patients with multiple
      sclerosis--a cohort study.
AB  - INTRODUCTION: Reduced working capability is one of the most devastating
      consequences of multiple sclerosis (MS). We aimed to study working capability and
      related variables in Swiss MS patients. MATERIALS AND METHODS: A cross-sectional
      analysis of employment status and risk factors for reduced working capability
      among MS patients treated at our outpatient clinic. A questionnaire was mailed to
      644 MS patients and returned by 69.7%. 405 patients (66% female, mean age 44.2
      years (SD +/- 10.2), median EDSS 3.0 (SD +/- 1.8)) were eligible for subsequent
      analysis. RESULTS: After a mean disease duration of 12.3 years (SD +/- 8.25),
      full or part time employment was declared by 26.7% and 25.7%, respectively.
      Incapacity to work was reported by 27.1%. A total of 52.8% specified MS as the
      cause for altered working capability, whereas 20.5% cited reasons unrelated to
      the disorder. Even with minimal disability (EDSS < 3) a significant proportion of
      patients (24%) reported reduced working capability. Among the MS-specific
      restricting factors were fatigue (47.6%), sensorimotor deficits (31.1%), impaired
      vision (3.3%) and pain (2.8%). CONCLUSION: MS continues to takes its toll on the
      professional life of the patients early in the course. While complete incapacity
      becomes relevant with moderate to severe disability, many patients scale down to
      part-time even with minimal impairment.

PMID- 25867209
TI  - Twenty-four hour hyperinsulinemic-euglycemic clamp improves postoperative
      nitrogen balance only in low insulin sensitivity patients following cardiac
      surgery.
AB  - BACKGROUND: Critically ill patients often suffer from a protein catabolic state.
      The aim of this study was to demonstrate that nitrogen balance (NB) in cardiac
      patients admitted to the intensive care unit (ICU) is related to their insulin
      sensitivity level and that supraphysiologic doses of insulin can restore
      anabolism. MATERIALS AND METHODS: Twenty-eight patients that were admitted to ICU
      in enteral and/or parenteral nutrition have been enrolled in this study. All
      patients received a standard nutrition protocol for at least 3 days before
      starting the study. These patients received either enteral or parenteral
      nutrition based on 1.4 kcal/kg/h and 1.1 g/kg/24 h of proteins. Participants were
      studied for three 24 h periods (P1 , P2 , and P3 ). Twenty-four hour NB was
      calculated from urinary urea nitrogen excretion, fixed protein and energy intake
      during each of the three periods (P1 , P2 , and P3 ). Simultaneous to P2, a 24 h
      hyperinsulinemic-euglycemic clamp (HEC) was performed to determine patients'
      insulin sensitivity (IS) or insulin resistance (IR), as well as the impact of
      high doses of insulin on NB. RESULTS: Nitrogen balance remained consistently
      positive in the IS group regardless of the clamp. In IR patients, NB was negative
      before the clamp and became positive during P2 and P3 . Insulin sensitivity
      improved during the HEC in IR patients (P < 0.001). CONCLUSIONS: A negative NB
      was found only in insulin resistant patients admitted to the ICU for more than 7
      days. A 24-h period HEC improved NB in these patients.

PMID- 25867211
TI  - Training Methods and Dog-Owner Interaction as a Public Health Risk Factor for Dog
      Bites.

PMID- 25867210
TI  - Managing skin and soft-tissue infection and nosocomial pneumonia caused by MRSA:
      a 2014 follow-up survey.
AB  - As a follow-up to our 2009 survey, in order to explore opinion and practice on
      the epidemiology and management of meticillin-resistant Staphylococcus aureus
      (MRSA) in Europe, we conducted a second survey to elicit current opinions on this
      topic, particularly around antibiotic choice, dose, duration and route of
      administration. We also aimed to further understand how the management of MRSA
      has evolved in Europe during the past 5 years. Members of an expert panel of
      infectious diseases specialists convened in London (UK) in January 2014 to
      identify and discuss key issues in the management of MRSA. Following this
      meeting, a survey was developed comprising 36 questions covering a wide range of
      topics on MRSA complicated skin and soft-tissue infection and nosocomial
      pneumonia management. The survey instrument, a web-based questionnaire, was sent
      to the International Society of Chemotherapy for distribution to registered
      European infection societies and their members. This article reports the survey
      results from the European respondents. At the time of the original survey, the
      epidemiology of MRSA varied significantly across Europe and there were differing
      views on best practice. The current findings suggest that the epidemiology of
      healthcare-associated MRSA in Europe is, if anything, even more polarised, whilst
      community-acquired MRSA has become much more common. However, there now appears
      to be a much greater knowledge of current treatment/management options, and
      antimicrobial stewardship has moved forward considerably in the 5 years since the
      last survey. 

PMID- 25867212
TI  - Wider retinal artery trajectories in eyes with macular hole than in fellow eyes
      of patients with unilateral idiopathic macular hole.
AB  - PURPOSE: To determine whether the width of the retinal artery (RA) trajectory was
      associated with the presence of a macular hole (MH). METHODS: A retrospective
      cross sectional case-control study was performed. The fundus photographs were
      rotated 90 degrees, and the coordinates of the best fit curve of the RA
      trajectory were determined automatically based on these plots using the ImageJ
      program. The converted coordinates were fit to a second degree polynomial
      (ax2/100 + bx + c) equation. The width and steepness of the RA trajectory, "a",
      of the eyes with a MH eye were compared to that of the fellow eyes. RESULTS: One
      hundred and ten eyes of 55 consecutive patients (30 women) with a unilateral MH
      and healthy fellow eyes were analyzed. The mean age was 64.9 years (range 47-81
      years). The constant 'a' was significantly smaller in eyes with a MH than that of
      the fellow eyes (0.379 +/- 0.094 vs 0.416 +/- 0.121, P = 0.001, paired t test),
      indicating that the RA trajectory was wider in the MH eyes than in the fellow
      eyes. There was a significant correlation between the axial length and 'a' of the
      RA trajectory in the MH eyes (R = 0.273, P = 0.044) and in the fellow eyes (R =
      0.356, P = 0.008; Spearman's rank correlation coefficient). CONCLUSIONS: Because
      eyes with a MH have a significantly wider and flatter RA trajectory, there may be
      greater traction on the fovea which is located between the RA arches. The
      causative role of this finding is still unclear.

PMID- 25867213
TI  - Heterodimer-specific TLR2 stimulation results in divergent functional outcomes in
      B-cell precursor acute lymphoblastic leukemia.
AB  - Reports of spontaneous acute lymphoblastic leukemia (ALL) remissions following
      severe bacterial infections suggest that bacterial components may trigger
      elimination of ALL. To date, TLR2, which recognizes a broad range of bacterial
      pathogens through TLR1 or TLR6 heterodimerization, has not been fully evaluated
      for direct effects on ALL. Studies investigating TLR2 signaling in other tumor
      cell types utilizing single ligands have yielded contradictory results, and
      comparative, heterodimer-specific analyses of TLR2 stimulation are lacking. In
      this study, we report that two well-characterized heterodimer-specific TLR2
      ligands, Pam3 CSK4 (TLR2/1), and Pam2 CSK4 (TLR2/6), induce ALL cell lines and
      primary ALL samples to upregulate CD40 expression. However, only Pam3 CSK4
      triggers Caspase-8-mediated apoptosis and sensitizes cells to vincristine
      mediated cytotoxicity. Consistent with this result, stimulation of ALL cells
      through TLR2/1 or TLR2/6 activates Mal, p38 and the NF-kappaB and PI3K signaling
      pathways with divergent kinetics that may underlie their distinct downstream
      effects. Our results reveal a novel branching in downstream responses to
      heterodimer-specific TLR2 stimulation in ALL cells and emphasize the need for
      comparative studies to determine differential biological effects observed in
      specific tumor cells. Based on our results, TLR2/1 ligand Pam3 CSK4 possesses
      potential for generating anti-ALL activity through its direct effects on leukemic
      blasts.

PMID- 25867214
TI  - Correction: Synergistic effect of viral load and alcohol consumption on the risk
      of persistent high-risk human papillomavirus infection.

PMID- 25867216
TI  - Electroretinogram analysis of the visual response in zebrafish larvae.
AB  - The electroretinogram (ERG) is a noninvasive electrophysiological method for
      determining retinal function. Through the placement of an electrode on the
      surface of the cornea, electrical activity generated in response to light can be
      measured and used to assess the activity of retinal cells in vivo. This
      manuscript describes the use of the ERG to measure visual function in zebrafish.
      Zebrafish have long been utilized as a model for vertebrate development due to
      the ease of gene suppression by morpholino oligonucleotides and pharmacological
      manipulation. At 5-10 dpf, only cones are functional in the larval retina.
      Therefore, the zebrafish, unlike other animals, is a powerful model system for
      the study of cone visual function in vivo. This protocol uses standard
      anesthesia, micromanipulation and stereomicroscopy protocols that are common in
      laboratories that perform zebrafish research. The outlined methods make use of
      standard electrophysiology equipment and a low light camera to guide the
      placement of the recording microelectrode onto the larval cornea. Finally, we
      demonstrate how a commercially available ERG stimulator/recorder originally
      designed for use with mice can easily be adapted for use with zebrafish. ERG of
      larval zebrafish provides an excellent method of assaying cone visual function in
      animals that have been modified by morpholino oligonucleotide injection as well
      as newer genome engineering techniques such as Zinc Finger Nucleases (ZFNs),
      Transcription Activator-Like Effector Nucleases (TALENs), and Clustered Regularly
      Interspaced Short Palindromic Repeats (CRISPR)/Cas9, all of which have greatly
      increased the efficiency and efficacy of gene targeting in zebrafish. In
      addition, we take advantage of the ability of pharmacological agents to penetrate
      zebrafish larvae to evaluate the molecular components that contribute to the
      photoresponse. This protocol outlines a setup that can be modified and used by
      researchers with various experimental goals. 

PMID- 25867215
TI  - Effects of non-equilibrium plasma in the treatment of ligature-induced peri
      implantitis.
AB  - AIM: To evaluate the effects of non-equilibrium plasma in the treatment of
      ligature-induced peri-implantitis in beagle dogs. MATERIALS AND METHODS: Six
      beagles received 12 implants installed in the position of the fourth mandibular
      premolars. Ligature-induced peri-implantitis was initiated at 3 months post
      implantation. When approximately 40% of the supporting bone was lost, the
      ligatures were removed. The implants were subjected to the muco-periosteal
      scaling and chlorhexidine irrigation with or without plasma irrigation. Three
      months later, clinical, radiographic and microbiological analyses were performed.
      Block biopsies were prepared for micro-CT and histomorphometric analysis. The
      primary outcome was the difference in bone healing of peri-implant sites, and the
      secondary outcomes included changes in clinical parameters (SBI, PD) and
      bacterial detection. RESULTS: At baseline, no significant differences were
      observed between the two groups. At 3 months post-treatment, the plasma group
      showed a significantly higher bone level than the control group (p < 0.05), a
      significantly decreased detection of bacteria (Porphyromonas gingivalis and
      Tannerella forsythia) (p < 0.05), and a significant improvement in clinical
      examination (p < 0.05). CONCLUSIONS: Within the limits of this study, non
      equilibrium plasma treatment as an adjunct to the conventional therapy is a
      feasible approach for the treatment of peri-implantitis.

PMID- 25867217
TI  - Genotoxic and Antigenotoxic Potential of Momordica charantia Linn (Cucurbitaceae)
      in the Wing Spot Test of Drosophila melanogaster.
AB  - Momordica charantia, popularly known as bitter melon, is a plant widely used in
      ethnobotanical medicine. It has antibacterial, antifungal, anthelmintic,
      antidiabetic, antiviral, and antimalarial activities, among others. The goal of
      this study was to evaluate the genotoxic and/or antigenotoxic activity of the
      aqueous extracts obtained from the aerial parts and fruit of this plant by means
      of the Drosophila melanogaster wing spot test. Third-stage larvae that obtained
      standard (ST) cross and high bioactivation (HB) cross were treated with aqueous
      extracts of the aerial parts (IQA) and fruit (IQF) of M. charantia, following two
      protocols (genotoxicity and antigenotoxicity). The aqueous extracts are not
      genotoxic in lower concentrations. The frequencies of mutant spots observed in
      the descendants of the ST and HB crosses treated with doxorubicin (DXR) alone
      were 8.65 and 9.25, respectively, whereas in those cotreated with IQA and DXR,
      the frequencies ranged from 15.90 to 29 in the ST cross and from 15.05 to 24.78
      in the HB cross. In cotreatment with IQF, the frequencies ranged from 30.10 to
      30.65 in the ST cross and from 13.60 to 14.50 in the HB cross, whereas the
      frequencies obtained with DXR were 32.50 in the ST cross and 26.00 in the HB
      cross. In conclusion, the IQA has a synergistic effect, enhancing the
      genotoxicity of DXR in the ST cross and the HB cross, whereas the IQF has
      antigenotoxic effects in the HB cross. 

PMID- 25867218
TI  - Multiscale modeling of the active site of [Fe] hydrogenase: the H2 binding site
      in open and closed protein conformations.
AB  - A series of QM/MM optimizations of the full protein of [Fe] hydrogenase were
      performed. The FeGP cofactor has been optimized in the water-bound resting state
      (1), with a side-on bound dihydrogen (2), or as a hydride intermediate (3). For
      inclusion of H4MPT in the closed structure, advanced multiscale modeling appears
      to be necessary, especially to obtain reliable distances between CH-H4MPT(+) and
      the dihydrogen (H2) or hydride (H(-)) ligand in the FeGP cofactor. Inclusion of
      the full protein is further important for the relative energies of the two
      intermediates 2 and 3. We finally find that hydride transfer from 3 has a
      significantly higher barrier than found in previous studies neglecting the full
      protein environment.

PMID- 25867220
TI  - Screening for hyperglycemia: the gateway to diabetes prevention and management
      for all Americans.

PMID- 25867219
TI  - Toll-like receptor (TLR) 2 agonists ameliorate indomethacin-induced murine
      ileitis by suppressing the TLR4 signaling.
AB  - BACKGROUND AND AIM: Few drugs have been found satisfactory in the treatment of
      nonsteroidal anti-inflammatory drugs (NSAIDs)-induced enteropathy. Toll-like
      receptor (TLR) 4 and aberrant leukocyte migration to the intestinal mucosa are
      reported to be involved in the pathology of intestinal enteropathy and TLR2
      agonists have been found to evoke hyposensitivity to TLR4 stimulation in vitro.
      In this study, we investigated whether and how lipoarabinomannan (LAM) or
      lipoteichoic acid (LTA), TLR2 agonists, attenuated indomethacin (IND)-induced
      intestinal damage. METHODS: LAM (0.5 mg/kg) or LTA (15 mg/kg) was administered
      intraperitoneally to mice before IND (10 mg/kg) administration. Disease activity
      was evaluated macroscopically and histologically. In the migration analysis,
      fluorescence-labeled leukocyte movement in the intestinal microvessels was
      observed by intravital microscopy. Expression of P-selectin, MAdCAM-1, TLR2,
      TLR4, and F4/80 was observed immunohistochemically. In the in vitro analysis,
      RAW264.7 macrophage cells were preincubated with LAM and stimulated with
      lipopolysaccharide (LPS), and the mRNA expression levels of TLR4, tumor necrosis
      factor-alpha, and interleukin-12p40 were measured. RESULTS: Pretreatment with LAM
      or LTA significantly decreased IND-induced injury as well as decreased leukocyte
      infiltration. Pretreatment with LAM decreased IND-induced TLR4 expression on
      F4/80(+) macrophages, the level of P-selectin expression, and leukocyte migration
      in the small intestinal vessels. In the in vitro study, a single administration
      of LAM decreased TLR4 mRNA expression and inhibited the increase in mRNA
      expression of inflammatory cytokines by LPS in a dose-dependent manner.
      CONCLUSION: TLR2 agonists attenuated IND-induced small intestinal lesions and
      leukocyte infiltration probably by suppressing the TLR4 signaling pathway in
      tissue macrophages.

PMID- 25867221
TI  - Large pupils predict goal-driven eye movements.
AB  - Here we report that large pupils predict fixations of the eye on low-salient,
      inconspicuous parts of a visual scene. We interpret this as showing that mental
      effort, reflected by a dilation of the pupil, is required to guide gaze toward
      objects that are relevant to current goals, but that may not be very salient.
      When mental effort is low, reflected by a constriction of the pupil, the eyes
      tend to be captured by high-salient parts of the image, irrespective of top-down
      goals. The relationship between pupil size and visual saliency was not driven by
      luminance or a range of other factors that we considered. Crucially, the
      relationship was strongest when mental effort was invested exclusively in eye
      movement control (i.e., reduced in a dual-task setting), which suggests that it
      is not due to general effort or arousal. Our finding illustrates that goal-driven
      control during scene viewing requires mental effort, and that pupil size can be
      used as an online measure to track the goal-drivenness of behavior.

PMID- 25867222
TI  - Visual perception involves event-type representations: The case of containment
      versus occlusion.
AB  - Recent infant cognition research suggests that core knowledge involves event-type
      representations: During perception, the mind automatically categorizes physical
      events into broad types (e.g., occlusion and containment), which then guide
      attention to different properties (e.g., with width processed at a younger age
      than height in containment events but not occlusion events). We tested whether
      this aspect of infant cognition also structures adults' visual processing. In 6
      experiments, adults had to detect occasional changes in ongoing dynamic displays
      that depicted repeating occlusion or containment events. Mirroring the
      developmental progression, change detection was better for width versus height
      changes in containment events, but no such difference was found for otherwise
      equivalent occlusion events, even though most observers were not even aware of
      the subtle occlusion-containment difference. These results suggest for the first
      time that event-type representations exist and operate automatically and
      unconsciously as part of the underlying currency of adult visual cognition.

PMID- 25867223
TI  - Simultaneous perceptual and response biases on sequential face attractiveness
      judgments.
AB  - Face attractiveness is a social characteristic that we often use to make first
      pass judgments about the people around us. However, these judgments are highly
      influenced by our surrounding social world, and researchers still understand
      little about the mechanisms underlying these influences. In a series of 3
      experiments, we use a novel sequential rating paradigm that enables us to measure
      biases in attractiveness judgments from the previous face and the previous
      rating. Our results reveal 2 simultaneous and opposing influences on face
      attractiveness judgments that arise from past experience of faces: a response
      bias in which attractiveness ratings shift toward a previously given rating and a
      stimulus bias in which attractiveness ratings shift away from the mean
      attractiveness of the previous face. Further, we provide evidence that the
      contrastive stimulus bias (but not the assimilative response bias) is
      strengthened by increasing the duration of the previous stimulus, suggesting an
      underlying perceptual mechanism. These results demonstrate that judgments of face
      attractiveness are influenced by information from our evaluative and perceptual
      history and that these influences have measurable behavioral effects over the
      course of just a few seconds.

PMID- 25867224
TI  - Mechanisms of social avoidance learning can explain the emergence of adaptive and
      arbitrary behavioral traditions in humans.
AB  - Many nonhuman animals preferentially copy the actions of others when the
      environment contains predation risk or other types of danger. In humans, the role
      of social learning in avoidance of danger is still unknown, despite the
      fundamental importance of social learning for complex social behaviors.
      Critically, many social behaviors, such as cooperation and adherence to religious
      taboos, are maintained by threat of punishment. However, the psychological
      mechanisms allowing threat of punishment to generate such behaviors, even when
      actual punishment is rare or absent, are largely unknown. To address this, we
      used both computer simulations and behavioral experiments. First, we constructed
      a model where simulated agents interacted under threat of punishment and showed
      that mechanisms' (a) tendency to copy the actions of others through social
      learning, together with (b) the rewarding properties of avoiding a threatening
      punishment, could explain the emergence, maintenance, and transmission of large
      scale behavioral traditions, both when punishment is common and when it is rare
      or nonexistent. To provide empirical support for our model, including the 2
      mechanisms, we conducted 4 experiments, showing that humans, if threatened with
      punishment, are exceptionally prone to copy and transmit the behavior observed in
      others. Our results show that humans, similar to many nonhuman animals, use
      social learning if the environment is perceived as dangerous. We provide a novel
      psychological and computational basis for a range of human behaviors
      characterized by the threat of punishment, such as the adherence to cultural
      norms and religious taboos.

PMID- 25867225
TI  - Interruptions disrupt reading comprehension.
AB  - Previous research suggests that being interrupted while reading a text does not
      disrupt the later recognition or recall of information from that text. This
      research is used as support for Ericsson and Kintsch's (1995) long-term working
      memory (LT-WM) theory, which posits that disruptions while reading (e.g.,
      interruptions) do not impair subsequent text comprehension. However, to fully
      comprehend a text, individuals may need to do more than recognize or recall
      information that has been presented in the text at a later time. Reading
      comprehension often requires individuals to connect and synthesize information
      across a text (e.g., successfully identifying complex topics such as themes and
      tones) and not just make a familiarity-based decision (i.e., recognition). The
      goal for this study was to determine whether interruptions while reading disrupt
      reading comprehension when the questions assessing comprehension require
      participants to connect and synthesize information across the passage. In
      Experiment 1, interruptions disrupted reading comprehension. In Experiment 2,
      interruptions disrupted reading comprehension but not recognition of information
      from the text. In Experiment 3, the addition of a 15-s time-out prior to the
      interruption successfully removed these negative effects. These data suggest that
      the time it takes to process the information needed to successfully comprehend
      text when reading is greater than that required for recognition. Any interference
      (e.g., an interruption) that occurs during the comprehension process may disrupt
      reading comprehension. This evidence supports the need for transient activation
      of information in working memory for successful text comprehension and does not
      support LT-WM theory.

PMID- 25867226
TI  - CINCA syndrome with surgical intervention for valgus deformity and flexion
      contracture of the knee joint: A case report.
AB  - Chronic infantile neurological, cutaneous, and articular (CINCA) syndrome is a
      systemic autoinflammatory disease caused by increased production of interleukin
      (IL)-1beta. We present a case of CINCA syndrome followed up to skeletal maturity.
      Joint contracture and valgus deformity of the knee had developed before
      diagnosis. Surgical interventions by soft tissue release and hemiepiphysiodesis
      improved the contracture and the deformity, and IL-1 receptor antagonist
      dramatically controlled systemic inflammation, and the patient lives without any
      disabilities.

PMID- 25867227
TI  - New onset of immunoglobulin G4-related disease in a patient with relapsing
      polychondritis.
AB  - Relapsing polychondritis (RP) is a rare systemic autoimmune disorder
      characterized by the episodic and progressive deterioration of cartilage
      inflammation. Approximately 30% patients with RP have concurrent disease.
      However, there have been no previous reports of RP complicated by immunoglobulin
      G4-related disease (IgG4-RD). Here we report the case of a 67-year-old male who
      developed IgG4-RD approximately 20 years after RP diagnosis. The association
      between IgG4-RD and RP remains unclear.

PMID- 25867229
TI  - Severe pes planovalgus successfully treated in a patient with mutilating
      rheumatoid arthritis using a new surgical approach involving medial malleolar
      resection and medial displacement of the talus: A case report.
AB  - We report the case of a 56-year-old female with mutilating rheumatoid arthritis,
      who developed severe pes planovalgus. The foot was successfully reconstructed
      through a combination of osteotomies, including medial displacement of the talus
      accompanied by resection of the medial malleolus. This maneuver enabled a ~1-cm
      medial displacement of the hindfoot while minimizing the adverse effect on
      forefoot rotation.

PMID- 25867228
TI  - IgG4-related disease manifesting as pericarditis with elevated adenosine
      deaminase and IL-10 levels in pericardial fluid.
AB  - A 78-year-old female with massive pericardial effusion fulfilled diagnostic
      criteria for immunoglobulin G4 (IgG4)-related disease. Although her adenosine
      deaminase (ADA) level in the pericardial effusion was high, all the tests for
      tuberculosis infection were negative. Immunostaining of the pericardium biopsy
      specimen revealed remarkably increased IgG4-positive cells. This is the first
      report describing IgG4-related pericarditis with elevated ADA level. We also
      demonstrate the elevated interleukin-10 (IL-10) level in pericardial fluid and IL
      10-producing T-cells in the pericardium.

PMID- 25867230
TI  - Effects of functional training on pain, leg strength, and balance in women with
      fibromyalgia.
AB  - AIM: The aim of this study was to analyze the effect of 18-week functional
      training (FT) program consisting in two sessions a week of in-water exercise and
      one of on-land exercise on pain, strength, and balance in women with
      fibromyalgia. METHODS: A sample consisting of 36 fibromyalgia patients was
      included in the study. The patients were allocated randomly into the experimental
      group (EG, n = 20), and control group (CG, n = 16). Standardized field-based
      fitness tests were used to assess muscle strength (30-s chair stand and handgrip
      strength) and agility/dynamic balance and static balance. Fibromyalgia impact and
      pain were analyzed by Fibromyalgia Impact Questionnaire (FIQ), tender points
      (TPs), visual analog scale (VAS). RESULTS: We observed a significant reduction in
      the FIQ (p = 0.042), the algometer scale of TP (p = 0.008), TP (p < 0.001), and
      VAS (p < 0.001) in the EG. The EG shows better results in leg strength (p <
      0.001), handgrip strength (p = 0.025), agility/dynamic balance (p = 0.032) and
      balance (p = 0.006). CONCLUSIONS: An 18-week intervention consisting in two
      sessions of in-water exercise and one session of on-land exercise of FT reduces
      pain and improves functional capacity in FM patients. These results suggested
      that FT could play an important role in maintaining an independent lifestyle in
      patients with FM.

PMID- 25867231
TI  - Henoch-Schonlein purpura nephritis occurring postpartum in a patient with anti-PL
      7 anti-synthetase syndrome.
AB  - A 37-year-old pregnant woman developed purpura which was subsequently diagnosed
      as Henoch-Schonlein purpura (HSP). After childbirth, the patient developed
      proteinuria and hematuria. Further examination revealed that the HSP nephritis
      (HSPN) was associated with anti-threonyl-tRNA synthetase anti-synthetase
      syndrome. The onset of HSPN during pregnancy or after childbirth is rare.
      Moreover, to our knowledge, this is the first case to describe renal involvement
      in anti-synthetase syndrome.

PMID- 25867232
TI  - Automated Breast Volume Scanner, a new automated ultrasonic device, is useful to
      examine joint injuries in patients with rheumatoid arthritis.
AB  - OBJECTIVE: To explore the clinical application of automated scanning of wrist and
      finger joints by an Automated Breast Volume Scanner (ABVS) in patients with
      rheumatoid arthritis (RA). METHODS: A total of 140 metacarpophalangeal (MCP)
      joints and 28 wrist joints from the 14 active RA patients were examined by both
      an ABVS system (the ACUSON S2000) from dorsal sites and by conventional
      ultrasonography (US) from multiple directions on the same day. We used a
      semiquantitative scale from 0 to 3 of synovial hypertrophy and the presence of
      bone erosion by grayscale for both methods; the efficacy of the two methods for
      identifying synovial hypertrophy and bone erosion were evaluated by kappa
      coefficient. RESULTS: The scanning time of the ABVS was 2 min per patient and
      that of conventional US was 15 min per patient. The kappa coefficients of
      synovial hypertrophy in the MCP joints were 0.60 and 0.79 in wrist joints. These
      values were increased in the joints where synovial hypertrophy was moderate to
      severe (scores greater than 2). The kappa coefficients for the presence of bone
      erosion in the MCP joints were 0.74 and 0.93 in wrist joints. CONCLUSION: The
      present data showed a substantial agreement between ABVS and conventional US for
      assessments of the synovial hypertrophy and bone erosion of wrist and finger
      joints in patients with RA. Since ABVS can scan the wrist and finger joints
      automatically in a short time, ABVS is a helpful new ultrasonic method to examine
      joint injuries in patients with RA.

PMID- 25867233
TI  - Dried blood spots--preparing and processing for use in immunoassays and in
      molecular techniques.
AB  - The idea of collecting blood on a paper card and subsequently using the dried
      blood spots (DBS) for diagnostic purposes originated a century ago. Since then,
      DBS testing for decades has remained predominantly focused on the diagnosis of
      infectious diseases especially in resource-limited settings or the systematic
      screening of newborns for inherited metabolic disorders and only recently have a
      variety of new and innovative DBS applications begun to emerge. For many years,
      pre-analytical variables were only inappropriately considered in the field of DBS
      testing and even today, with the exception of newborn screening, the entire pre
      analytical phase, which comprises the preparation and processing of DBS for their
      final analysis has not been standardized. Given this background, a comprehensive
      step-by-step protocol, which covers al the essential phases, is proposed, i.e.,
      collection of blood; preparation of blood spots; drying of blood spots; storage
      and transportation of DBS; elution of DBS, and finally analyses of DBS eluates.
      The effectiveness of this protocol was first evaluated with 1,762 coupled
      serum/DBS pairs for detecting markers of hepatitis B virus, hepatitis C virus,
      and human immunodeficiency virus infections on an automated analytical platform.
      In a second step, the protocol was utilized during a pilot study, which was
      conducted on active drug users in the German cities of Berlin and Essen. 

PMID- 25867234
TI  - The value of cell cycle analysis by propidium-iodine staining of CD56+ cells in
      pediatric brain tumors.
AB  - PURPOSE: Cell cycle analysis by flow cytometry has not been adequately studied in
      pediatric brain tumors. We investigated the value of cell cycle analysis by
      propidium-iodine (PI) staining of CD56+ (gated) cells for the characterization of
      pediatric brain tumor's malignancy. METHODS: Patients that underwent surgery for
      an intracranial lesion and tissue sample was available were included in the
      study. All tumor samples were histopathologically verified before flow cytometric
      analysis. RESULTS: There were 46 pediatric brain tumor cases. As control we used
      samples from three cases of brain tissue obtained during surgery for epilepsy.
      All tumors had significant lower G0/G1 and significant higher S-phase, G2/M
      fraction, S+G2/M and S+G2/M/G0/G1-phase fraction than normal brain tissue. Low
      grade tumors had significant lower S-phase than high grade tumors. Grade IV
      tumors had significant lower G0/G1 fraction and higher S+G2/M/G0/G1 index than
      grade III tumors. DNA diploidy was detected in 24 tumors and DNA aneuploidy was
      detected in 23 tumors. There was a significant correlation between Ki-67 index
      and both S+G2/M and S+G2/M/G0/G1 phase fraction. CONCLUSIONS: Cell cycle analysis
      by PI staining of CD56+ cells is a promising method for the assessment of
      pediatric brain tumors malignancy and could be a valuable adjunct to
      histopathological evaluation.

PMID- 25867235
TI  - Technical modifications and decision-making to reduce morbidity in thoracic disc
      surgery: An institutional experience and treatment algorithm.
AB  - BACKGROUND: Symptomatic thoracic disc herniation (TDH) is an uncommon condition
      with significant treatment risks. OBJECTIVE: To evaluate strategies to avoid and
      manage complications from thoracic disc surgery. METHODS: All TDH cases by the
      senior author were retrospectively reviewed from 2000 to 2012. Complications were
      recorded, together with avoidance and management strategies. To reduce access
      related morbidity, a thoracoscopic-tubular retractor approach was developed later
      in the series. RESULTS: 64 patients were treated for TDH, the majority undergoing
      an anterior minimally-invasive approach. Complications occurred in 15 patients
      (23%). Three patients with intercostal neuralgia persisting for >3 months had
      pain resolution after intercostal nerve blocks and radiofrequency lesioning. Five
      of the six patients with dural tears during anterior surgery had no further
      events following dural repair, lumbar drain insertion, and placement of chest
      tube to water seal. One case of persistent CSF leakage was successfully treated
      with a laparoscopically-mobilized omental flap. Preoperative metallic marker
      placement was effective at guiding correct-level surgery. For anterior
      operations, no pneumothorax occurred with routine chest tube placement. Our
      approach and techniques evolved based on early experience, allowing us to reduce
      surgical morbidity. The thoracoscopic-tubular retractor approach was associated
      with low morbidity (no complications among 13 cases other than temporary
      intercostal neuralgia). CONCLUSIONS: Several strategies may reduce morbidity from
      thoracic disc surgery: careful approach selection, preoperative level marking,
      use a tubular retractor with thoracoscopic guidance, rib resection at the mini
      thoracotomy site, routine chest tube placement for anterior operations, and
      routine lumbar drain insertion in the event of a dural tear. Prospective
      comparative studies are needed to assess the efficacy of these techniques.

PMID- 25867236
TI  - Intraoperative neuromonitoring for removal of large vestibular schwannoma: Facial
      nerve outcome and predictive factors.
AB  - BACKGROUND: Preservation of facial nerve (FN) function is one of the major goals
      for resection of large vestibular schwannoma (VS) (>= 30 mm). Little is known
      about the FN outcome and its predictive factors due to limited data. OBJECTIVE:
      To explore the predictive factors affecting FN outcome following resection of
      large VS. METHODS: 106 Large VS patients underwent surgical resection from 2010
      to 2012 via intraoperative neuromonitoring for FN preservation approach.
      Postoperative FN function evaluation was conducted at the time points of 3-7th
      day, 3rd month and at the end of the 2nd year. Correlation between tumor size,
      intraoperative parameters and FN function were examined. RESULTS: The ratios of
      total and subtotal resection were 82.1% and 14.2%, respectively. Acceptable FN
      function was achieved in 78% patients. Patients with good FN function showed much
      smaller (P < 0.01) VS size than those of poor-FN function patients at 3-7th day,
      3rd month and 2nd year. There was a significant correlation between facial motor
      evoked potential (FMEP) ratios and postoperative FN function at 3-7th day (r = 
      0.709, P < 0.001) 3rd month (r = -0.709, P< 0.001) and 2nd year (r = -0.750, P <
      0.001). Maximal response amplitude (MRA) ratio was a supplementary indicator for
      train time in predicting both immediate and long-term FN function in patients
      with large VS. CONCLUSION: Indicative factors of both immediate and long-term
      postoperative FN function in large VSs include tumor size, intraoperative train
      time, start to final FMEP ratios and proximal to distal MRA ratios.

PMID- 25867238
TI  - Effects of Equisetum arvense Ointment on Diabetic Wound Healing in Rats.
AB  - This study is designed to evaluate the effect of Equisetum arvense (EA) ointment
      on dermal diabetic wound healing in streptozotocin-induced diabetic rats.
      METHODS: In this study, diabetes was induced via a single intraperitoneal
      injection of 65 mg/kg streptozotocin in 56 male Wistar rats. After
      anesthetization, a 15 mm x 15 mm wound for each rat was made by removing skin in
      a circle on the dorsum. A total of 56 diabetic wounds were studied in 8 groups (n
      = 7), 4 of which were treated with EA ointment. On the 7th and 14th days after
      creating the wounds, the state of the diabetic wound healing was evaluated with
      wound closure ratio and by performing histopathologic studies. RESULTS: Groups
      treated with EA 5%-10% ointment were found to have a statistically higher wound
      closure ratio than control and petroleum jelly-lanolin groups (P < 0.05). On day
      14, groups to which EA 5%-10% ointment was applied showed 99.71% and 99.93% wound
      closure ratio (P < 0.05) and higher dermal and epidermal regeneration,
      angiogenesis, and granulation tissue thickness after 14 days than the other
      groups (P < 0.05). CONCLUSION: These results indicate that EA ointments exhibit
      significant diabetic wound healing activity in excision wounds. Further clinical
      and experimental studies are needed to confirm these results.

PMID- 25867237
TI  - Decrease of Functional Activated T and B Cells and Treatment of Glomerulonephitis
      in Lupus-Prone Mice Using a Natural Flavonoid Astilbin.
AB  - Treatment of systemic lupus erythematosus (SLE), a chronic inflammatory disease,
      involves the long-term use of immunosuppressive agents with significant side
      effects. New therapeutic approaches are being explored to find better treatment
      possibilities. In this study, age-matched female MRL/lpr mice were treated orally
      with a natural flavonoid astilbin. Astilbin administration started either at week
      8 or week 12 of age though week 20. In the early treatment regimen, the treatment
      with astilbin reduced splenomegaly/lymphomegaly, autoantibody production and
      ameliorated lupus nephritis. Several serum cytokines were significantly decreased
      upon treatment including IFN-g, IL-17A, IL-1b, TNF-a and IL-6. Both spleen CD44
      hi CD62L lo activated T cells and CD138+B220- plasma cells greatly declined.
      Furthermore, astilbin treatment resulted in decreased mitochondrial membrane
      potential in activated T cells and downregulated expression of the co-stimulatory
      molecules CD80 and CD86 on LPS stimulated B cells. Similar but less profound
      effectiveness was observed in the mice with established disease in the late
      treatment regimen. These results indicate that the natural product astilbin can
      mitigate disease development in lupus-prone mice by decreasing functional
      activated T and B cells.

PMID- 25867239
TI  - An evidence-based algorithm for treating venous leg ulcers utilizing the cochrane
      database of systematic reviews.
AB  - BACKGROUND: This literature review serves to develop an evidence-based algorithm
      for the treatment of venous ulcerations and the development of a guideline to
      systemically treat venous leg ulcerations (VLUs) that may improve outcomes,
      restore function of the affected limb, and reduce health care costs. METHODS: The
      Cochrane Database and PubMed search engine were utilized to accumulate literature
      concerning venous ulcerations and their treatment. The most relevant literature
      was reviewed to develop an algorithm to guide treatment of VLUs. RESULTS: An
      algorithm was established outlining the use of compression therapy in VLUs
      present for < 4 weeks. If a wound is present after 4 weeks of therapy and has not
      reduced in size by >= 40%, bilayered living skin equivalents may be indicated.
      CONCLUSION: An algorithm was established to guide the treatment of venous
      ulcerations. By utilizing a systematic approach in treating VLUs, clinical
      outcomes may be improved.    .

PMID- 25867240
TI  - Treatment of infection with improved pulsed lavage.
AB  - OBJECTIVE: To develop a more effective surgical lavage technique to improve the
      efficacy of treatment for infections after a tibia/fibula fracture. METHODS: A
      retrospective analysis was performed on 46 patients who received pulsed lavage
      with a side-hole double-valve lavage tube in the Second Hospital of Tangshan,
      Tangshan, China. Patients with the same injury treated with conventional lavage
      techniques in the same period were used as controls. The lavage success rate and
      the infection cure rate were analyzed to evaluate this therapy. RESULTS: All
      patients showed wound healing by first intention, and there was no recurrence
      during the follow-up period of > 12 months. Compared to the control group, the
      group that received pulsed lavage showed higher lavage success rates and cure
      rates. CONCLUSION: Pulsed lavage therapy with a side-hole double-valve lavage
      tube can improve the efficacy of treatment infections after tibia/fibula
      fractures and constitutes an effective modification to conventional lavage
      techniques.  .

PMID- 25867241
TI  - Platelet-rich plasma in skin ulcer treatment.
AB  - INTRODUCTION: Chronic vascular ulcers are associated with a high use of
      resources. Conventional treatment consists of wound cleansing, necrotic tissue
      debridement, prevention, diagnosis, and, if necessary, treatment of infection and
      dressing application; although conventional treatment has limited effectiveness
      with wound healing (around 15-30%).8-11 Platelet-rich plasma, used in various
      fields of medicine, improves chronic vascular ulcer results, but is more
      expensive. METHODS: A cost-effectiveness analysis was performed using a 48-week
      period comparing plateletrich plasma with standard care. A meta-analysis of
      papers identified by a literature search was done. RESULTS: A combined measure of
      effectiveness at 12 weeks for each treatment option was calculated and served as
      the basis for estimating the probability of healing at 48 weeks with a Markov
      model. CONCLUSIONS: The probability of healing and associated costs were 56% and
      ?5224 using platelet-rich plasma and 31% and ?5133 with usual care. The
      incremental cost that must be assumed to achieve additional healing with platelet
      rich plasma is ?364.    .

PMID- 25867242
TI  - Assessing a safe interval for subsequent negative pressure wound therapy change
      after initial placement in acute, contaminated wounds.
AB  - BACKGROUND: Negative pressure wound therapy (NPWT) is empirically expanding
      across the globe. Yet published data with NPWT in acute, contaminated wounds is
      limited, and several concerns arise regarding contemporary acute wound care NPWT
      practice. Specifically, there are no evidence-based time intervals specifying
      when NPWT should be changed after initial placement in such cases; therefore,
      NPWT was studied in acute, contaminated wounds. METHODS: The authors
      retrospectively reviewed 86 consecutive patients, and a total of 97 contaminated
      wounds. All wounds were class IV, based on Centers for Disease Control and
      Prevention (CDC) criteria. All patients were managed with NPWT. Patient and wound
      specific variables were analyzed. Outcome endpoints included durability of wound
      closure and death. RESULTS: Mean time of subsequent NPWT after initial placement
      was 2.9 days, median time 3 days, mode 2 days, and standard deviation (SD) 1.24
      days. Durability of wound closure was 73/79 (92%). Deaths were noted in 6/86 (7%)
      of patients. No deaths appeared related to NPWT. CONCLUSIONS: Based on the
      findings in this study, analyzing NPWT in the largest known patient cohort of
      this type, a time interval of 1.7 days to 4.1 days (mean time 2.9 days, SD 1.24),
      between initial and subsequent placement of NPWT in acute, contaminated wounds is
      safe and effective.

PMID- 25867244
TI  - The cancer which survived: insights from the genome of an 11000 year-old cancer.
AB  - The canine transmissible venereal tumour (CTVT) is a transmissible cancer that is
      spread between dogs by the allogeneic transfer of living cancer cells during
      coitus. CTVT affects dogs around the world and is the oldest and most divergent
      cancer lineage known in nature. CTVT first emerged as a cancer about 11000 years
      ago from the somatic cells of an individual dog, and has subsequently acquired
      adaptations for cell transmission between hosts and for survival as an allogeneic
      graft. Furthermore, it has achieved a genome configuration which is compatible
      with long-term survival. Here, we discuss and speculate on the evolutionary
      processes and adaptions which underlie the success of this remarkable lineage.

PMID- 25867245
TI  - Correction: Characterization of the murine myeloid precursor cell line MuMac-E8.

PMID- 25867243
TI  - Contrast imaging in mouse embryos using high-frequency ultrasound.
AB  - Ultrasound contrast-enhanced imaging can convey essential quantitative
      information regarding tissue vascularity and perfusion and, in targeted
      applications, facilitate the detection and measure of vascular biomarkers at the
      molecular level. Within the mouse embryo, this noninvasive technique may be used
      to uncover basic mechanisms underlying vascular development in the early mouse
      circulatory system and in genetic models of cardiovascular disease. The mouse
      embryo also presents as an excellent model for studying the adhesion of
      microbubbles to angiogenic targets (including vascular endothelial growth factor
      receptor 2 (VEGFR2) or alphavbeta3) and for assessing the quantitative nature of
      molecular ultrasound. We therefore developed a method to introduce ultrasound
      contrast agents into the vasculature of living, isolated embryos. This allows
      freedom in terms of injection control and positioning, reproducibility of the
      imaging plane without obstruction and motion, and simplified image analysis and
      quantification. Late gestational stage (embryonic day (E)16.6 and E17.5) murine
      embryos were isolated from the uterus, gently exteriorized from the yolk sac and
      microbubble contrast agents were injected into veins accessible on the chorionic
      surface of the placental disc. Nonlinear contrast ultrasound imaging was then
      employed to collect a number of basic perfusion parameters (peak enhancement,
      wash-in rate and time to peak) and quantify targeted microbubble binding in an
      endoglin mouse model. We show the successful circulation of microbubbles within
      living embryos and the utility of this approach in characterizing embryonic
      vasculature and microbubble behavior. 

PMID- 25867246
TI  - Methods for comparing nutrients in beebread made by Africanized and European
      honey bees and the effects on hemolymph protein titers.
AB  - Honey bees obtain nutrients from pollen they collect and store in the hive as
      beebread. We developed methods to control the pollen source that bees collect and
      convert to beebread by placing colonies in a specially constructed enclosed
      flight area. Methods were developed to analyze the protein and amino acid
      composition of the pollen and beebread. We also describe how consumption of the
      beebread was measured and methods used to determine adult worker bee hemolymph
      protein titers after feeding on beebread for 4, 7 and 11 days after emergence.
      Methods were applied to determine if genotype affects the conversion of pollen to
      beebread and the rate that bees consume and acquire protein from it. Two
      subspecies (European and Africanized honey bees; EHB and AHB respectively) were
      provided with the same pollen source. Based on the developed methods, beebread
      made by both subspecies had lower protein concentrations and pH values than the
      pollen. In general, amino acid concentrations in beebread made by either EHB or
      AHB were similar and occurred at higher levels in beebread than in pollen. Both
      AHB and EHB consumed significantly more of the beebread made by AHB than by EHB.
      Though EHB and AHB consumed similar amounts of each type of beebread, hemolymph
      protein concentrations in AHB were higher than in EHB. Differences in protein
      acquisition between AHB and EHB might reflect environmental adaptations related
      to the geographic region where each subspecies evolved. These differences could
      contribute to the successful establishment of AHB populations in the New World
      because of the effects on brood rearing and colony growth. 

PMID- 25867247
TI  - Self-assembly of monodisperse starburst carbon spheres into hierarchically
      organized nanostructured supercapacitor electrodes.
AB  - We report a three-dimensional (3D) porous carbon electrode containing both
      nanoscale and microscale porosity, which has been hierarchically organized to
      provide efficient ion and electron transport. The electrode organization is
      provided via the colloidal self-assembly of monodisperse starburst carbon spheres
      (MSCSs). The periodic close-packing of the MSCSs provides continuous pores inside
      the 3D structure that facilitate ion and electron transport (electrode electrical
      conductivity ~0.35 S m(-1)), and the internal meso- and micropores of the MSCS
      provide a good specific capacitance. The capacitance of the 3D-ordered porous
      MSCS electrode is ~58 F g(-1) at 0.58 A g(-1), 48% larger than that of disordered
      MSCS electrode at the same rate. At 1 A g(-1) the capacitance of the ordered
      electrode is 57 F g(-1) (95% of the 0.24 A g(-1) value), which is 64% greater
      than the capacitance of the disordered electrode at the same rate. The ordered
      electrode preserves 95% of its initial capacitance after 4000
      charging/discharging cycles. 

PMID- 25867248
TI  - Systemic lupus erythematosus: molecular cloning and analysis of 22 individual
      recombinant monoclonal kappa light chains specifically hydrolyzing human myelin
      basic protein.
AB  - Antibodies hydrolyzing myelin basic protein (MBP) can play an important role in
      the pathogenesis of multiple sclerosis (MS) and systemic lupus erythematosus
      (SLE). An immunoglobulin light chain phagemid library derived from peripheral
      blood lymphocytes of patients with SLE was used. Small pools of phage particles
      displaying light chains with different affinities for MBP were isolated by
      affinity chromatography on MBP-Sepharose, and the fraction eluted with 0.5 M NaCl
      was used for preparation of individual monoclonal light chains (MLChs, 26-27
      kDa). Seventy-two of 440 individual colonies were randomly chosen, expressed in
      Escherichia coli in a soluble form, and MLChs were purified by metal chelating
      chromatography. Twenty-two of 72 MLChs have high affinity and efficiently
      hydrolyze only MBP (not other control proteins) demonstrating various pH optima
      in a 5.7-9.0 range and different substrate specificity in the hydrolysis of four
      different MBP oligopeptides. Four MLChs demonstrated serine protease-like and
      three thiol protease-like activities, while 11 MLChs were metalloproteases. The
      activity of three MLChs was inhibited by both phenylmethylsulfonyl fluoride
      (PMSF) and Ethylenediaminetetraacetic acid (EDTA), two other by EDTA and
      iodoacetamide, and one by PMSF, EDTA, and iodoacetamide. The ratio of relative
      activity in the presence of Ca(2+), Mg(2+), Mn(2+), Ni(2+), Zn(2+), Cu(2+), and
      Co(2+) was individual for each of 22 MLCh preparations. It is the first examples
      of human MLChs, which probably can possess two or even three different
      proteolytic activities. These observations suggest an extreme diversity of anti
      MBP abzymes in SLE patients. The immune systems of individual SLE patients can
      generate a variety of anti-MBP abzymes, which can attack MBP of myelin
      proteolipid sheath of axons and play an important role in MS and SLE
      pathogenesis.

PMID- 25867249
TI  - The gender health gap in China: A decomposition analysis.
AB  - Around the world, and in spite of their higher life expectancy, women tend to
      report worse health than men until old age. Explanations for this gender gap in
      self-perceived health may be different in China than in other countries due to
      the traditional phenomenon of son preference. We examine several possible reasons
      for the gap using the Chinese SAGE data. We first rule out differential reporting
      by gender as a possible explanation, exploiting information on anchoring
      vignettes in eight domains of health functioning. Decomposing the gap in general
      self-assessed health, we find that about 31% can be explained by socio
      demographic factors, most of all by discrimination against women in education in
      the 20th century. A more complete specification including chronic conditions and
      health functioning fully explains the remainder of the gap (about 69%). Adding
      chronic conditions and health functioning also explains at least two thirds of
      the education contribution, suggesting how education may affect health. In
      particular, women's higher rates of arthritis, angina and eye diseases make the
      largest contributions to the gender health gap, by limiting mobility, increasing
      pain and discomfort, and causing sleep problems and a feeling of low energy. 

PMID- 25867250
TI  - Fabrication of ordered mullite nanowhisker array with surface enhanced Raman
      scattering effect.
AB  - Mullite nanowhiskers are prepared by a facile technique at low temperature using
      mica and AlF3 as raw material. Mica acts as reactant as well as substrate. By
      controlling the reaction temperature and holding time, the mullite nanowhisker
      array with uniform morphology is obtained. The nanowhisker array possesses Al
      rich single crystalline with an average of 80 nm in diameter and 20 MUm in
      length. After decorated with Au nanoparticles, the array exhibits high surface
      enhanced Raman scattering (SERS) activity with an SERS enhancement factor (EF) of
      1.35 * 10(9). It also remains good SERS signal detection with a relative standard
      deviation of 7.33% under corrosion condition. 

PMID- 25867251
TI  - Effect of developmental care for very premature infants on neurodevelopmental
      outcome at 2 years of age.
AB  - BACKGROUND: To determine the effect of developmental care on neurodevelopmental
      outcome in formerly preterm infants at a corrected age of 2 years. METHODS: A
      prospective phase-lag study was performed at an Austrian neonatal intensive care
      unit (NICU). From January 2003 to December 2005 (study period of conventional
      care) and January 2007 to December 2009 (study period of developmental care), we
      enrolled all infants born in Tyrol at less than 32 weeks of gestation. During
      this period a total of 261 of 359 preterm infants (participation rate 72.7%)
      completed the follow-up visit at 2 years of age; there were 124 children in the
      conventional and 137 in the developmental care group. The association between
      developmental care and delayed motor or mental development (Bayley Scales of
      Infant Development II; psychomotor or mental developmental index <85) was
      analyzed by means of logistic regression analysis at a corrected age of 24
      months. RESULTS: Children in the developmental care group showed less psychomotor
      delay than did those in the control group (developmental care group: 16.1%,
      conventional care group 27.4%; adjusted odds ratio 0.37 [95% confidence interval:
      0.19-0.74], P=0.005). Not smoking in pregnancy and higher gestational age were
      also significant predictors for a better psychomotor outcome at 2 years of age.
      Regarding cognitive outcome, no significant difference was observed between these
      two groups. CONCLUSION: Our data implicate that developmental care may result in
      an improved 2-year psychomotor outcome in formerly preterm infants.

PMID- 25867252
TI  - A new technique for quantitative analysis of hair loss in mice using grayscale
      analysis.
AB  - Alopecia is a common form of hair loss which can occur in many different
      conditions, including male-pattern hair loss, polycystic ovarian syndrome, and
      alopecia areata. Alopecia can also occur as a side effect of chemotherapy in
      cancer patients. In this study, our goal was to develop a consistent and reliable
      method to quantify hair loss in mice, which will allow investigators to
      accurately assess and compare new therapeutic approaches for these various forms
      of alopecia. The method utilizes a standard gel imager to obtain and process
      images of mice, measuring the light absorption, which occurs in rough proportion
      to the amount of black (or gray) hair on the mouse. Data that has been quantified
      in this fashion can then be analyzed using standard statistical techniques (i.e.,
      ANOVA, T-test). This methodology was tested in mouse models of chemotherapy
      induced alopecia, alopecia areata and alopecia from waxing. In this report, the
      detailed protocol is presented for performing these measurements, including
      validation data from C57BL/6 and C3H/HeJ strains of mice. This new technique
      offers a number of advantages, including relative simplicity of application,
      reliance on equipment which is readily available in most research laboratories,
      and applying an objective, quantitative assessment which is more robust than
      subjective evaluations. Improvements in quantification of hair growth in mice
      will improve study of alopecia models and facilitate evaluation of promising new
      therapies in preclinical studies. 

PMID- 25867253
TI  - Curcumin inhibits apoptosis and brain edema induced by hypoxia-hypercapnia brain
      damage in rat models.
AB  - Curcumin, extracted from South Asian spice turmeric, has been determined to have
      the promising ability in antioxidation and anti-inflammation. However, the effect
      of curcumin on treating brain damage has been not reported. In this article, the
      aim was to evaluate the effect of curcumin on cell apoptosis in rats exposed to
      hypoxia-hypercapnia and explore the therapeutic potential of curcumin in hypoxia
      hypercapnia brain damage (HHBD). Sprague Dawley rats were randomly assigned into
      3 groups: control group, hypoxia-hypercapnia group and curcumin group. The
      Fas/FasL expressions in HHBD rats treated by curcumin were measured by
      immunohistochemical staining and western blotting. The pathological changes of
      brain cells were observed by transmission electron microscope. Rats with HHBD
      showed significant increase of Fas/FasL expression and ultrastructural changes in
      brain tissue cells. Curcumin intervention effectively reversed the Fas/FasL
      mediated apoptosis and HHBD-induced brain edema. Curcumin may be a potential
      therapeutic alternative for HHBD. 

PMID- 25867254
TI  - Bacterial Endocarditis Complicated by Leukocytoclastic Vasculitis.

PMID- 25867255
TI  - Prevalence and change of malocclusions from primary to early permanent dentition:
      a longitudinal study.
AB  - OBJECTIVE: To follow a group of children from primary to early permanent
      dentition and determine the prevalence, self-correction, and new development of
      malocclusions; the need for orthodontic treatment; and the possible influences of
      habits, breathing disturbances, and allergies. MATERIALS AND METHODS: Two hundred
      and seventy-seven children were followed at 3, 7, and 11.5 years of age.
      Malocclusions and orthodontic treatment need were determined by clinical
      examinations. Data on sucking habits, breathing disturbances, allergies, dental
      trauma, and orthodontic treatments were collected from a questionnaire and dental
      records. RESULTS: Malocclusions were found in 71% of participants at 3 years of
      age, 56% at 7 years of age, and 71% at 11.5 years of age. Self-correction was
      noted for anterior open bite, sagittal malocclusions, and posterior crossbite,
      while deep bite developed. A high number of contact point displacements and
      spacings contributed to the prevalence of malocclusion rate of 71% at 11.5 years.
      Severe or extreme orthodontic treatment need was apparent in 22%. Habits,
      allergies, or breathing disturbances found at 3 years of age had no associations
      with malocclusions at 11.5 years of age. CONCLUSIONS: This sample revealed a
      significant percentage of malocclusions and orthodontic treatment need. A
      substantial number of self-corrections and establishment of new malocclusions
      occurred during the transition from primary to early permanent dentition.

PMID- 25867256
TI  - Lymphoma incidence, survival and prevalence 2004-2014: sub-type analyses from the
      UK's Haematological Malignancy Research Network.
AB  - BACKGROUND: Population-based information about cancer occurrence and survival are
      required to inform clinical practice and research; but for most lymphomas data
      are lacking. METHODS: Set within a socio-demographically representative UK
      population of nearly 4 million, lymphoma data (N=5796) are from an established
      patient cohort. RESULTS: Incidence, survival (overall and relative) and
      prevalence estimates for >20 subtypes are presented. With few exceptions, males
      tended to be diagnosed at younger ages and have significantly (P<0.05) higher
      incidence rates. Differences were greatest at younger ages: the <15 year
      male/female rate ratio for all subtypes combined being 2.2 (95% CI 1.3-3.4).
      These gender differences impacted on prevalence; most subtype estimates being
      significantly (P<0.05) higher in males than females. Outcome varied widely by
      subtype; survival of patients with nodular lymphocyte predominant Hodgkin
      lymphoma approached that of the general population, whereas less than a third of
      those with other B-cell (e.g., mantle cell) or T-cell (e.g., peripheral-T)
      lymphomas survived for >=5 years. No males/female survival differences were
      detected. CONCLUSIONS: Major strengths of our study include completeness of
      ascertainment, world-class diagnostics and generalisability. The marked
      variations demonstrated confirm the requirement for 'real-world' data to inform
      aetiological hypotheses, health-care planning and the future monitoring of
      therapeutic changes.

PMID- 25867257
TI  - Prognostic value of histological type in stage IV ovarian carcinoma: a
      retrospective analysis of 223 patients.
AB  - BACKGROUND: Patients with FIGO stage IV epithelial ovarian carcinoma have a poor
      but non-uniform prognosis. This study aimed to compare the survival of patients
      with serous or endometrioid tumours (S/E) and clear cell or mucinous tumours (non
      S/E). METHODS: Data for 223 patients who underwent surgery between 1987 and 2010
      and were diagnosed by centralized pathology review and were retrospectively
      analysed. The patients included 169 with S/E tumours and 54 with non-S/E tumours.
      RESULTS: The median overall survivals (OSs) of the S/E and non-S/E groups were
      3.1 and 0.9 years, respectively (P<0.001). Six patients (2.7%), all with non-S/E
      tumours, died within 6 weeks after the initial surgery. Multivariate OS analysis
      revealed that performance status, residual tumor, metastatic sites, no debulking
      surgery, and non-S/E tumours were independent poor prognostic factors. For
      patients with non-S/E tumours, prognosis was more favourable for single-organ
      metastasis, except for liver or distant lymph nodes, no residual tumor, and
      resection of metastasis (median OS: 4.1, 4.6, and 2.6 years, respectively).
      CONCLUSIONS: In stage IV ovarian carcinoma, non-S/E tumours are associated with a
      significantly poorer prognosis and higher rates of early mortality compared to
      S/E tumours. Therefore, careful management and development of new strategies are
      required.

PMID- 25867260
TI  - Comment on: 'vitamin D supplements and cancer incidence and mortality: a meta
      analysis'.

PMID- 25867259
TI  - Cytokine profiling of docetaxel-resistant castration-resistant prostate cancer.
AB  - BACKGROUND: Docetaxel improves symptoms and survival in metastatic castration
      resistant prostate cancer (CRPC). However, ~50% of patients are chemoresistant.
      This study examined whether changes in cytokine levels predict for docetaxel
      resistance in vitro and in a clinical cohort. METHODS: PC3 cells or their
      docetaxel-resistant subline (PC3Rx) were co-cultured with U937 monocytes, with
      and without docetaxel treatment, and cytokine levels were measured. The
      circulating levels of 28 cytokines were measured pre-/post cycle 1 of docetaxel
      from 55 men with CRPC, and compared with prostate-specific antigen (PSA)
      response. RESULTS: PC3Rx-U937 co-culture expressed more cytokines, chiefly
      markers of alternative macrophage differentiation, compared with PC3-U937 co
      culture. Docetaxel treatment enhanced cytokine production by PC3Rx-U937 co
      culture, while reducing cytokine levels in PC3-U937. In patients, changes in the
      levels of seven circulating cytokines (macrophage inhibitory cytokine 1 (MIC1),
      interleukin (IL)-1ra, IL-1beta, IL-4, IL-6, IL-12 and IFNgamma) after cycle 1 of
      docetaxel were associated with progressive disease (all P<0.05). The combination
      of changes in MIC1, IL-4 and IL-6 most strongly predicted PSA response (P=0.002).
      CONCLUSIONS: In vitro studies suggest docetaxel resistance is mediated, at least
      in part, by cytokines induced by the interaction between the docetaxel-resistant
      tumour cells and macrophages. Early changes in circulating cytokine levels were
      associated with docetaxel resistance in CRPC patients. When considered together,
      these data suggest a significant role for the inflammatory response and
      macrophages in the development of docetaxel resistance in CRPC.

PMID- 25867258
TI  - Lifestyle and reproductive risk factors associated with anal cancer in women aged
      over 50 years.
AB  - BACKGROUND: Anal cancer incidence increases with age and is higher in women than
      men. Risk factors in this group other than high-risk human papillomavirus
      infection are unclear. METHODS: In all, 1.3 million women were recruited in 1996
      2001 and followed for incident anal cancer. Cox regression models were used to
      calculate relative risks (RRs) for anal cancer by various potential risk factors.
      RESULTS: Five hundred and seventeen incident anal cancers were registered over 13
      years of follow-up. The largest RR was associated with a history of cervical
      intraepithelial neoplasia grade 3 (CIN 3; RR=4.03, 95% CI 2.59-6.28). Other
      factors associated with significantly increased risks in multivariate analyses
      were: ever smoking (RR=1.49, 1.24-1.80); previous use of oral contraceptives
      (RR=1.51, 1.24-1.83); nulliparity (RR=1.61, 1.24-2.07); tubal ligation (RR=1.39,
      1.13-1.70) and not living with a partner (RR=1.82, 1.40-2.38). The association
      with smoking was significantly greater for squamous cell carcinoma than
      adenocarcinoma of the anus (RR 1.66 vs 0.89, P for heterogeneity=0.04).
      CONCLUSIONS: History of CIN 3, smoking, past oral contraceptive use, nulliparity,
      tubal ligation and not living with a partner are risk factors for anal cancer in
      women. There was a significant increase in risk associated with smoking for
      squamous cell anal cancers but not adenocarcinomas.

PMID- 25867261
TI  - Combining bevacizumab and chemoradiation in rectal cancer. Translational results
      of the AXEBeam trial.
AB  - BACKGROUND: This study characterises molecular effect of bevacizumab, and
      explores the relation of molecular and genetic markers with response to
      bevacizumab combined with chemoradiotherapy (CRT). METHODS: From a subset of 59
      patients of 84 rectal cancer patients included in a phase II study combining
      bevacizumab with CRT, tumour and blood samples were collected before and during
      treatment, offering the possibility to evaluate changes induced by one dose of
      bevacizumab. We performed cDNA microarrays, stains for CD31/CD34 combined with
      alpha-SMA and CA-IX, as well as enzyme-linked immunosorbent assay (ELISA) for
      circulating angiogenic proteins. Markers were related with the pathological
      response of patients. RESULTS: One dose of bevacizumab changed the expression of
      14 genes and led to a significant decrease in microvessel density and in the
      proportion of pericyte-covered blood vessels, and a small but nonsignificant
      increase in hypoxia. Alterations in angiogenic processes after bevacizumab
      delivery were only detected in responding tumours. Lower PDGFA expression and
      PDGF-BB levels, less pericyte-covered blood vessels and higher CA-IX expression
      were found after bevacizumab treatment only in patients with pathological
      complete response. CONCLUSIONS: We could not support the 'normalization
      hypothesis' and suggest a role for PDGFA, PDGF-BB, CA-IX and alpha-SMA.
      Validation in larger patient groups is needed.

PMID- 25867262
TI  - Benzene exposure and risk of lymphohaematopoietic cancers in 25 000 offshore oil
      industry workers.
AB  - BACKGROUND: The aim of this work was to examine the risk of lymphohaematopoietic
      (LH) cancer according to benzene exposure among offshore workers. METHODS: Cancer
      registry data were used to identify 112 cancer cases diagnosed during 1999-2011
      in a cohort of 24 917 Norwegian men reporting offshore work between 1965 and
      1999. Analyses were conducted according to a stratified case-cohort design with a
      reference subcohort of 1661 workers. Cox regression was used to estimate hazard
      ratios with 95% confidence intervals, adjusted for other benzene exposure and
      smoking. RESULTS: Most workers were exposed to benzene for <15 years. The upper
      range values of average intensity and cumulative exposure were estimated to 0.040
      p.p.m. and 0.948 p.p.m.-years, respectively. Risks were consistently elevated
      among exposed workers for all LH cancers combined and for most subgroups,
      although case numbers were small and yielded imprecise risk estimates. There was
      evidence of dose-related risk patterns according to cumulative exposure for acute
      myeloid leukaemia (AML), multiple myeloma (MM) (P trends 0.052 and 0.024,
      respectively), and suggestively so for chronic lymphocytic leukaemia (CLL)
      according to average intensity (P trend 0.094). CONCLUSIONS: Our results support
      an association between cumulative and intensity metrics of low-level benzene
      exposure and risk for AML, MM, and suggestively for CLL.

PMID- 25867263
TI  - Circulating tumour cells and outcome in non-metastatic colorectal cancer: a
      prospective study.
AB  - BACKGROUND: Circulating tumour cells (CTC) in the blood have been accepted as a
      prognostic marker in patients with metastatic colorectal cancer (CRC). Only
      limited data exist on the prognostic impact of CTC in patients with early stage
      CRC using standardised detection assays. The aim of this study was to elucidate
      the role of CTC in patients with non-metastatic CRC. METHODS: A total of 287
      patients with potentially curable CRC were enrolled, including 239 patients with
      UICC stage I-III. CTC were measured in the blood using the CellSearch system
      preoperatively and on postoperative days 3 and 7. The complete patient group
      (UICC I-IV) and the non-metastatic cohort (UICC I-III) were analysed
      independently. Patients were followed for 28 (0-53) months. Prognostic factors
      for overall and progression-free survival were analysed using univariate and
      multivariate analyses. RESULTS: CTC were detected more frequently in patients
      with metastatic disease. No clinicopathological variables were associated with
      CTC detection in non-metastatic patients. CTC detection (?1 CTC per 7.5 ml blood)
      in the blood was significantly associated with worse overall survival (49.8 vs
      38.4 months; P<0.001) in the non-metastatic group (UICC I-III), as well as in the
      complete cohort (48.4 vs 33.6 months; P<0.001). On multivariate analysis CTC were
      the strongest prognostic factor in non-metastatic patients (hazard ratio (HR)
      5.5; 95% confidence interval (CI) 2.3-13.6) as well as in the entire study group
      (HR 5.6; 95% CI 2.6-12.0). CONCLUSIONS: Preoperative CTC detection is a strong
      and independent prognostic marker in non-metastatic CRC.

PMID- 25867264
TI  - IFN-gamma from lymphocytes induces PD-L1 expression and promotes progression of
      ovarian cancer.
AB  - BACKGROUND: PD-L1 (programmed cell death 1 ligand 1) on tumour cells suppresses
      host immunity through binding to its receptor PD-1 on lymphocytes, and promotes
      peritoneal dissemination in mouse models of ovarian cancer. However, how PD-L1
      expression is regulated in ovarian cancer microenvironment remains unclear.
      METHODS: The number of CD8-positive lymphocytes and PD-L1 expression in tumour
      cells was assessed in ovarian cancer clinical samples. PD-L1 expression and
      tumour progression in mouse models under conditions of altering IFN-gamma signals
      was assessed. RESULTS: The number of CD8-positive cells in cancer stroma was very
      high in peritoneally disseminated tumours, and was strongly correlated to PD-L1
      expression on the tumour cells (P<0.001). In mouse models, depleting IFNGR1
      (interferon-gamma receptor 1) resulted in lower level of PD-L1 expression in
      tumour cells, increased the number of tumour-infiltrating CD8-positive
      lymphocytes, inhibition of peritoneal disseminated tumour growth and longer
      survival (P=0.02). The injection of IFN-gamma into subcutaneous tumours induced
      PD-L1 expression and promoted tumour growth, and PD-L1 depletion completely
      abrogated tumour growth caused by IFN-gamma injection (P=0.01). CONCLUSIONS:
      Interferon-gamma secreted by CD8-positive lymphocytes upregulates PD-L1 on
      ovarian cancer cells and promotes tumour growth. The lymphocyte infiltration and
      the IFN-gamma status may be the key to effective anti-PD-1 or anti-PD-L1 therapy
      in ovarian cancer.

PMID- 25867265
TI  - MIC-1/GDF15 in Barrett's oesophagus and oesophageal adenocarcinoma.
AB  - BACKGROUND: Biomarkers are needed to improve current diagnosis and surveillance
      strategies for patients with Barrett's oesophagus (BO) and oesophageal
      adenocarcinoma (OAC). Macrophage inhibitory cytokine 1/growth differentiation
      factor 15 (MIC-1/GDF15) tissue and plasma levels have been shown to predict
      disease progression in other cancer types and was therefore evaluated in BO/OAC.
      METHODS: One hundred thirty-eight patients were studied: 45 normal oesophagus
      (NE), 37 BO, 16 BO with low-grade dysplasia (LGD) and 40 OAC. RESULTS: Median
      tissue expression of MIC-1/GDF15 mRNA was ?25-fold higher in BO and LGD compared
      to NE (P<0.001); two-fold higher in OAC vs BO (P=0.039); and 47-fold higher in
      OAC vs NE (P<0.001). Relative MIC-1/GDF15 tissue expression >720 discriminated
      between the presence of either OAC or LGD vs NE with 94% sensitivity and 71%
      specificity (ROC AUC 0.86, 95% CI 0.73-0.96; P<0.001). Macrophage inhibitory
      cytokine 1/growth differentiation factor 15 plasma values were also elevated in
      patients with OAC vs NE (P<0.001) or BO (P=0.015).High MIC-1/GDF15 plasma levels
      (?1140 pg ml(-1)) were an independent predictor of poor survival for patients
      with OAC (HR 3.87, 95% CI 1.01-14.75; P=0.047). CONCLUSIONS: Plasma and tissue
      levels of MIC-1/GDF15 are significantly elevated in patients with BO, LGD and
      OAC. Plasma MIC-1/GDF15 may have value in diagnosis and monitoring of Barrett's
      disease.

PMID- 25867266
TI  - Inflammatory breast cancer: time to standardise diagnosis assessment and
      management, and for the joining of forces to facilitate effective research.

PMID- 25867267
TI  - Efficient and reproducible generation of tumour-infiltrating lymphocytes for
      renal cell carcinoma.
AB  - BACKGROUND: Tumour-infiltrating lymphocyte (TIL) therapy is showing great promise
      in the treatment of patients with advanced malignant melanoma. However, the
      translation of TIL therapy to non-melanoma tumours such as renal cell carcinoma
      has been less successful with a major constraint being the inability to
      reproducibly generate TILs from primary and metastatic tumour tissue. METHODS:
      Primary and metastatic renal cell carcinoma biopsies were subjected to
      differential tumour disaggregation methods and procedures that stimulate the
      specific expansion of TILs tested to determine which reliably generated TIL
      maintained antitumour specificity. RESULTS: Enzymatic or combined
      enzymatic/mechanical disaggregation resulted in equivalent numbers of TILs being
      liberated from renal cell carcinoma biopsies. Following mitogenic activation of
      the isolated TILs with anti-CD3/anti-CD28-coated paramagnetic beads, successful
      TIL expansion was achieved in 90% of initiated cultures. The frequency of T-cell
      recognition of autologous tumours was enhanced when tumours were disaggregated
      using the GentleMACS enzymatic/mechanical system. CONCLUSION: TILs can be
      consistently produced from renal cell carcinoma biopsies maintaining autologous
      tumour recognition after expansion in vitro. While the method of disaggregation
      has little impact on the success of TIL growth, methods that preserve the cell
      surface architecture facilitate TIL recognition of an autologous tumour, which is
      important in terms of characterising the functionality of the expanded TIL
      population.

PMID- 25867268
TI  - Activating GNAS and KRAS mutations in gastric foveolar metaplasia, gastric
      heterotopia, and adenocarcinoma of the duodenum.
AB  - BACKGROUND: Heterotopic gastric-type epithelium, including gastric foveolar
      metaplasia (GFM) and gastric heterotopia (GH), is a common finding in duodenal
      biopsy specimens; however, there is still controversy regarding their
      histogenetic backgrounds. METHODS: We analysed a total of 177 duodenal lesions,
      including 66 GFM lesions, 81 GH lesions, and 30 adenocarcinomas, for the presence
      of GNAS, KRAS, and BRAF mutations. RESULTS: Activating GNAS mutations were
      identified in 27 GFM lesions (41%) and 23 GH lesions (28%). The KRAS mutations
      were found in 17 GFM lesions (26%) and 2 GH lesions (2%). A BRAF mutation was
      found in only one GFM lesion (2%). These mutations were absent in all 32 normal
      duodenal mucosa specimens that were examined, suggesting a somatic nature. Among
      the GFM lesions, GNAS mutations were more common in lesions without active
      inflammation. Analyses of adenocarcinomas identified GNAS and KRAS mutations in 5
      (17%) and 11 lesions (37%), respectively. Immunohistochemically, all the GNAS
      mutated adenocarcinomas diffusely expressed MUC5AC, indicating gastric epithelial
      differentiation. CONCLUSIONS: A significant proportion of GFM and GH harbours
      GNAS and/or KRAS mutations. The common presence of these mutations in duodenal
      adenoma and adenocarcinoma with a gastric epithelial phenotype implies that GFM
      and GH might be precursors of these tumours.

PMID- 25867269
TI  - Comment on: 'vitamin D supplements and cancer incidence and mortality: a meta
      analysis'.

PMID- 25867270
TI  - Detection of HPV-associated oropharyngeal tumours in a 16-year cohort: more than
      meets the eye.
AB  - BACKGROUND: Accurate assessment of the prevalence of the human papilloma virus
      (HPV) in oropharyngeal tumours (OpSCC) is important because HPV-positive OpSCC
      are consistently associated with an improved overall survival. Recently, an
      algorithm has become available that reliably detects clinically relevant HPV in
      tumour tissue, however, no complete cohorts have been tested. The aim was to
      determine the prevalence of active high-risk HPV infection in a complete cohort
      of OpSCC collected over a 16-year period. METHODS: Using a triple algorithm of
      p16 immunohistochemistry, HPV-BRISH and HPV-PCR, we assessed the prevalence of
      active HPV infection in all OpSCC diagnosed in our hospital from 1997 to 2012
      (n=193) and a random selection of 200 oral tumours (OSCC). RESULTS: Forty-seven
      OpSCC (24%) were HPVGP PCR-positive; 42 cases were HPV16+, 1 HPV18+, 3 HPV33+ and
      1 HPV35+. Brightfield in situ hybridisation did not identify additional HPV
      positive cases. Human papilloma virus-associated tumour proportion increased from
      13% (1997-2004) to 30% (2005-2012). Human papilloma virus-positivity was an
      independent predictor for longer disease-specific survival (HR=0.22; 95%CI:0.10
      0.47). Only one OSCC was HPV+. CONCLUSIONS: In our cohort, the incidence of HPV
      associated OpSCC is low but increasing rapidly. The strict detection algorithm,
      analysis of disease-specific survival and the complete cohort, including
      palliatively treated patients, may influence the reported prevalence and
      prognostic value of HPV in OpSCC.

PMID- 25867271
TI  - miR-367 promotes epithelial-to-mesenchymal transition and invasion of pancreatic
      ductal adenocarcinoma cells by targeting the Smad7-TGF-beta signalling pathway.
AB  - BACKGROUND: Aberrant Smad7 expression contributes to the invasion and metastasis
      of pancreatic cancer cells. However, the potential mechanism underlying aberrant
      Smad7 expression in human pancreatic ductal adenocarcinoma (PDAC) remains largely
      unknown. METHODS: Bioinformatic prediction programmes and luciferase reporter
      assay were used to identify microRNAs regulating Smad7. The association between
      miR-367 expression and the overall survival of PDAC patients was evaluated by
      Kaplan-Meier analysis. The effects of miR-367 and Smad7 on the invasion and
      metastasis of pancreatic cancer cells were investigated both in vitro and in
      vivo. RESULTS: We found that miR-367 downregulated Smad7 expression by directly
      targeting its 3'-UTR in human pancreatic cancer cells. High level of miR-367
      expression correlated with poor prognosis of PDAC patients. Functional studies
      showed that miR-367 promoted pancreatic cancer invasion in vitro and metastasis
      in vivo through downregulating Smad7. In addition, we showed that miR-367
      promoted epithelial-to-mesenchymal transition by increasing transforming growth
      factor-beta (TGF-beta)-induced transcriptional activity. CONCLUSIONS: The present
      study identified and characterised a signalling pathway, the miR-367/Smad7-TGF
      beta pathway, which is involved in the invasion and metastasis of pancreatic
      cancer cells. Our results suggest that miR-367 may be a promising therapeutic
      target for the treatment of human pancreatic cancer.

PMID- 25867272
TI  - The combination of axitinib followed by paclitaxel/carboplatin yields extended
      survival in advanced BRAF wild-type melanoma: results of a clinical/correlative
      prospective phase II clinical trial.
AB  - BACKGROUND: Simultaneous chemotherapy with vascular endothelial growth factor
      (VEGF) inhibition has not shown additional benefit over chemotherapy alone in
      advanced melanoma. We tested administration of the potent VEGF inhibitor axitinib
      followed by paclitaxel/carboplatin to determine whether enhanced tumour
      proliferation during axitinib withdrawal leads to sustained chemosensitivity.
      METHODS: We conducted a prospective phase II trial in metastatic melanoma
      patients with ECOG performance status 0-1 and normal organ function. Axitinib 5
      mg PO b.i.d. was taken on days 1-14 of each 21-day treatment cycle, and
      carboplatin (AUC=5) with paclitaxel (175 mg m(-2)) was administered on day 1
      starting with cycle 2. 3'-Deoxy-3'-(18)F-fluorothymidine ((18)F-FLT)-PET scans
      were performed in five patients to assess tumour proliferation on days 1, 14, 17,
      and 20 of cycle 1. Molecular profiling for BRAF was performed for all patients
      with cutaneous, acral, or mucosal melanoma. RESULTS: The treatment was well
      tolerated. The most common grade 3 AEs were hypertension, neutropenia, and
      anaemia. Grade 4 non-haematologic AEs were not observed. Four of five patients
      completing (18)F-FLT-PET scans showed increases (23-92%) in SUV values during the
      axitinib holiday. Of 36 evaluable patients, there were 8 confirmed PRs by
      Response Evaluation Criteria in Solid Tumors. Overall, 20 patients had SD and 8
      had PD as the best response. The median PFS was 8.7 months and the median overall
      survival was 14.0 months. Five BRAF(V600E/K) patients had significantly worse PFS
      than patients without these mutations. CONCLUSIONS: Axitinib followed by
      carboplatin and paclitaxel was well tolerated and effective in BRAF wild-type
      metastatic melanoma. 3'-Deoxy-3'-(18)F-fluorothymidine-PET scans showed increased
      proliferation during axitinib withdrawal.

PMID- 25867273
TI  - The oncomiR miR-197 is a novel prognostic indicator for non-small cell lung
      cancer patients.
AB  - BACKGROUND: MicroRNA expression signatures can promote personalised care for non
      small cell lung cancer (NSCLC) patients. Our aim was to evaluate the previously
      unexplored prognostic potential of miR-197, a key oncogenic molecule for NSCLC.
      METHODS: Total RNA isolation (n=124 NSCLC and n=21 tumour-adjacent normal
      tissues), was performed using the QIAsymphony SP workstation. The quantity and
      quality of RNA were assessed by spectrophotometric analysis and an Agilent 2100
      bioanalyzer. Polyadenylation and reverse transcription were subsequently carried
      out. MiR-197 expression levels were measured by qPCR, after quality control
      (inter-assay CV=7.8%). Internal validation procedures were followed by assigning
      training and test sets and robust biostatistical analyses were performed,
      including bootstrap resampling. RESULTS: MiR-197 is associated with larger
      tumours (P=0.042) and the squamous cell carcinoma histotype (P=0.032).
      Interestingly, after adjusting for important prognostic indicators, miR-197
      expression was identified as a novel independent predictor of unfavourable
      prognosis for NSCLC patients (HR=1.97, 95% CI=1.10-3.38, P=0.013). We also
      demonstrate that miR-197 retains its prognostic performance in both early-stage I
      (P=0.045) and more advanced-stage individuals (P=0.036). CONCLUSIONS: The cost
      effective expression analysis of miR-197 could constitute a novel molecular tool
      for NSCLC management.

PMID- 25867274
TI  - The genomic expression test EndoPredict is a prognostic tool for identifying risk
      of local recurrence in postmenopausal endocrine receptor-positive, her2neu
      negative breast cancer patients randomised within the prospective ABCSG 8 trial.
AB  - BACKGROUND: The aim of this study was to examine whether EndoPredict (EP), a
      novel genomic expression test, is effective in predicting local recurrence (LR)
      free survival (LRFS) following surgery for breast cancer in postmenopausal women.
      In addition, we examined whether EP may help tailor local therapy in these
      patients. METHODS: From January 1996 to June 2004, 3714 postmenopausal patients
      were randomly assigned to either tamoxifen or tamoxifen followed by anastrozole
      within the prospective ABCSG 8 trial. Using assay scores from EP, we classified
      breast tumour blocks as either low or high risk for recurrence. RESULTS: Data
      were gathered from 1324 patients. The median follow-up was 72.3 months and the
      cumulative incidence of LR was 2.6% (0.4% per year). The risk of LR over a 10
      year period among patients with high-risk lesions (n=683) was significantly
      higher (LRFS=91%) when compared with patients with low-risk lesions (n=641) (10
      year LRFS=97.5%) (HR: 1.31 (1.16-1.48) P<0.005). The groups that received breast
      conservation surgery (BCT) and mastectomy (MX) had similar LR rates (P=0.879).
      Radiotherapy (RT) after BCT significantly improved LRFS in the cohorts predicted
      by EP to be low-risk for LR (received RT: n=436, 10-year LRFS 99.8%; did not
      receive RT: n=63, 10-year LRFS 83.6%, P<0.005). CONCLUSIONS: EndoPredict is an
      effective prognostic tool for predicting LRFS. Among postmenopausal, low-risk
      patients, EP does not appear to be useful for tailoring local therapy.

PMID- 25867275
TI  - Phosphoglycerate kinase-1 is a predictor of poor survival and a novel prognostic
      biomarker of chemoresistance to paclitaxel treatment in breast cancer.
AB  - BACKGROUND: Phosphoglycerate kinase-1 (PGK1) has been recently documented in
      various malignancies; however, the molecular mechanisms of the variable PGK1
      expression and its clinical significance in terms of survival status remain
      unclear. METHODS: Real-time quantitative PCR (real-time qPCR) and western
      blotting were used to verify PGK1 expression in 46 fresh breast cancer tissues
      and matched normal tissues. A tissue microarray (TMA) comprising 401 breast
      cancer tissues and 123 matched normal tissues was investigated by
      immunohistochemistry for PGK1 expression. Then, the correlation between PGK1
      expression and the clinicopathologic features was analysed. RESULTS: PGK1 mRNA
      and protein expression were significantly increased in breast cancer tissues
      compared with that in normal breast tissues. High PGK1 expression was
      significantly associated with higher histologic grade (P=0.009) and positive
      status of ER (P=0.004), Her-2 (P=0.026) and P53 (P=0.012). High levels of PGK1
      expression were associated with worse overall survival (OS, P=0.02). Furthermore,
      patients who underwent paclitaxel chemotherapy with high levels PGK1 expression
      had shorter OS than did those with low levels of PGK1 expression (P<0.001).
      Multivariate analysis indicated that PGK1 (P=0.001) was an independent predictor
      in the patients treated with paclitaxel. CONCLUSIONS: PGK1 is a prognostic
      biomarker of chemoresistance to paclitaxel treatment in breast cancer.

PMID- 25867277
TI  - Coverage of defect over toes after failure of microsurgical replantation with
      medial sural artery perforator flap: A case report.
AB  - In this report, we present a case of toe reconstruction with a medial sural
      artery perforator free flap after failure of replantation. A 35-year-old male
      suffered a crush injury from a heavy object falling over the left 1st, 2nd, and
      3rd toes and underwent microsurgical replantation of the toes at an outside
      facility. Over the next 2 weeks, ischemic necrosis of all the toes developed.
      This condition was very frustrating for the patient who had very high
      expectations of preserving the toes, and also for the surgeon to determine the
      optimal method to reconstruct the distal foot and toes. After debridement of non
      viable tissues, the defect over the toes was resurfaced using a medial sural
      artery perforator free flap and full thickness skin graft. Subsequently, several
      minor operations, including interdigitation, excision of neuromas, and defatting
      procedure were performed to complete his reconstruction. Eighteen months later,
      the patient had very aesthetically pleasing and fully functional toes. A medial
      sural artery perforator free flap may be used to repair the soft tissue defect on
      the toes after failed replantation, and provides sufficient skin.

PMID- 25867276
TI  - C/EBP-beta-activated microRNA-223 promotes tumour growth through targeting RASA1
      in human colorectal cancer.
AB  - BACKGROUND: Evidences have shown that the RAS signalling pathway plays an
      important role in colorectal cancer (CRC). Moreover, RAS-GTPase-activating
      proteins (RASGAPs) as RAS signalling terminators are associated with
      tumourigenicity and tumour progression. In this study, we used bioinformatics
      analysis to predict and study important miRNAs that could target RAS p21 GTPase
      activating protein 1 (RASA1), an important member of RASGAPs. METHODS: The levels
      of RASA1 and miR-223 were analysed by real-time PCR, western blotting or in situ
      immunofluorescence analyses. The functional effects of miR-223 and the effects of
      miR-223-targeted inhibitors were examined in vivo using established assays.
      RESULTS: Upregulation of miR-223 was detected in CRC tissues (P<0.01) and was
      involved in downregulation of RASA1 in CRC tissues. Furthermore, the direct
      inhibition of RASA1 translation by miR-223 and the activation of miR-223 by
      CCAAT/enhancer binding protein-beta (C/EBP-beta) were evaluated in CRC cells. An
      in vivo xenograft model of CRC suggested that the upregulation of miR-223 could
      promote tumour growth and that the inhibition of miR-223 might prevent solid
      tumour growth. CONCLUSIONS: These results identify that C/EBP-beta-activated miR
      223 contributes to tumour growth by targeting RASA1 in CRC and miR-223-targeted
      inhibitors may have clinical promise for CRC treatment via suppression of miR
      223.

PMID- 25867278
TI  - Outcome of international Federation of gynecology and obstetrics stage IIb
      cervical cancer from 2003 to 2012: an evaluation of treatments and prognosis: a
      retrospective study.
AB  - OBJECTIVE: To compare the clinical outcomes of patients with International
      Federation of Gynecology and Obstetrics (FIGO) stage IIB cervical carcinoma
      receiving neoadjuvant chemotherapy followed by radical hysterectomy (RH) with
      those of patients receiving chemoradiation therapy (CRT) alone. METHODS: We
      retrospectively reviewed the medical records of patients with FIGO stage IIB
      cervical carcinoma. A total of 621 patients were eligible for the study according
      to the surgery-based or radiotherapy-based treatment; 285 patients received
      cisplatin-based neoadjuvant chemotherapy (NACT) followed by RH, and 336 patients
      underwent sequential or concurrent chemoradiation. The disease-free survival,
      overall survival, recurrence rates, and late complications were compared. Cox
      regression analysis was used to identify potential prognostic factors. RESULTS:
      Complete or partial response was seen in 77.6% (221/285) of the NACT-treated
      patients. Disease-free survival and overall survival rates of the patients who
      had NACT-sensitive responses were significantly higher than those who did not
      response (P = 0.021 and P = 0.008). Overall survival rates in the NACT + RH group
      were comparable with the concurrent chemoradiotherapy or chemoradiation groups (P
      > 0.05). Neoadjuvant chemotherapy followed by RH significantly decreased the
      recurrence rate (22.6% vs 35.5%), resulted in fewer treatment-related
      complications, and ultimately improved survival when compared with concurrent
      CRT. A survival benefit was observed for 63.9% of the patients in the NACT + RH
      group without adjuvant radiotherapy or CRT. CONCLUSIONS: Compared with concurrent
      chemoradiotherapy, NACT followed by RH achieved comparable survival outcomes for
      patients with FIGO stage IIB cervical cancer. This treatment method was
      significantly effective at reducing radiotherapy rates and complications, and it
      is worthy of recommending for younger patients.

PMID- 25867279
TI  - Lactobacillus reuteri glyceraldehyde-3-phosphate dehydrogenase functions in
      adhesion to intestinal epithelial cells.
AB  - This study was aimed to identify key surface proteins mediating the adhesion of
      lactobacilli to intestinal epithelial cells. By using Caco-2 and IPEC-J2 cells
      labeled with sulfo-NHS-biotin in the western blotting, a protein band of an
      approximately 37 kDa was detected on the surface layer of Lactobacillus reuteri
      strains ZJ616, ZJ617, ZJ621, and ZJ623 and Lactobacillus rhamnosus GG. Mass
      spectrometry analysis using the adhesion-related protein from L. reuteri ZJ617
      showed that it was 100% homologous to the glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH) of L. reuteri JCM 1112 (GenBank: YP_001841377). The ability
      of L. reuteri ZJ617 to adhere to epithelial cells decreased significantly by
      treatment with LiCl or by blocking with an anti-GAPDH antibody, in comparison
      with the untreated strain (p < 0.05). Immunoelectron microscopic and
      immunofluorescence analyses confirmed that GAPDH is located on the surface layer
      of L. reuteri ZJ617. The results indicated that the GAPDH protein of L. reuteri
      ZJ617 acts as an adhesion component that plays an important role in binding to
      the intestinal epithelial cells. 

PMID- 25867280
TI  - Oral Anticoagulant Prescription in Patients With Atrial Fibrillation and a Low
      Risk of Thromboembolism: Insights From the NCDR PINNACLE Registry.

PMID- 25867282
TI  - Investigating single molecule adhesion by atomic force spectroscopy.
AB  - Atomic force spectroscopy is an ideal tool to study molecules at surfaces and
      interfaces. An experimental protocol to couple a large variety of single
      molecules covalently onto an AFM tip is presented. At the same time the AFM tip
      is passivated to prevent unspecific interactions between the tip and the
      substrate, which is a prerequisite to study single molecules attached to the AFM
      tip. Analyses to determine the adhesion force, the adhesion length, and the free
      energy of these molecules on solid surfaces and bio-interfaces are shortly
      presented and external references for further reading are provided. Example
      molecules are the poly(amino acid) polytyrosine, the graft polymer PI-g-PS and
      the phospholipid POPE (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine).
      These molecules are desorbed from different surfaces like CH3-SAMs, hydrogen
      terminated diamond and supported lipid bilayers under various solvent conditions.
      Finally, the advantages of force spectroscopic single molecule experiments are
      discussed including means to decide if truly a single molecule has been studied
      in the experiment. 

PMID- 25867281
TI  - Redox Regulation of Pro-IL-1beta Processing May Contribute to the Increased
      Severity of Serum-Induced Arthritis in NOX2-Deficient Mice.
AB  - AIMS: To elucidate the role of reactive oxygen species (ROS) in arthritis and to
      identify targets of arthritis treatment in conditions with different levels of
      oxidant stress. RESULTS: Through establishing an arthritis model by injecting
      arthritogenic serum into wild-type and NADPH oxidase 2 (NOX2)-deficient mice, we
      found that arthritis had a neutrophilic infiltrate and was more severe in Ncf1(-/
      ) mice, a mouse strain lacking the expression of the NCF1/p47(phox) component of
      NOX2. The levels of interleukin-1beta (IL-1beta) and IL-6 in inflamed joints were
      higher in Ncf1(-/-) than in controls. Antagonists of tumor necrosis factor-alpha
      (TNFalpha) and IL-1beta were equally effective in suppressing arthritis in wild
      type mice, while IL-1beta blockade was more effective than TNFalpha blockade in
      Ncf1(-/-) mice. A treatment of caspase inhibitor and the combination treatment of
      a caspase inhibitor and a cathepsin inhibitor, but not a cathepsin inhibitor
      alone, suppressed arthritic severity in the wild-type mice, while a treatment of
      cathepsin inhibitor and the combination treatment of a caspase inhibitor and a
      cathepsin inhibitor, but not a caspase inhibitor alone, were effective in
      treating Ncf1(-/-) mice. Consistently, cathepsin B was found to proteolytically
      process pro-IL-1beta to its active form and this activity was suppressed by ROS.
      INNOVATION: This novel mechanism of a redox-mediated immune regulation of
      arthritis through leukocyte-produced ROS is important for devising an optimal
      treatment for patients with different levels of tissue ROS. CONCLUSION: Our
      results suggest that ROS act as a negative feedback to constrain IL-1beta
      mediated inflammation, accounting for the more severe arthritis in the absence of
      NOX2.

PMID- 25867283
TI  - Fluorescent dyes with directly connected xanthone and xanthene units.
AB  - Unexpected dimerization of a methoxymethyl-protected xanthone occurred upon
      treatment with an aryl lithium reagent generated from 2-bromo-1,3-dimethylbenzene
      and n-butyllithium. The hydrogen between two directing ethereal oxygen atoms was
      not abstracted, but that adjacent to the carbonyl group was removed to afford a
      dimeric compound containing two directly connected fluorescent xanthone and
      xanthene units. Starting from this discovery, three dimeric dyes were
      constructed, and their optical properties were examined. Although the two
      fluorescent units were orthogonal in each dye, efficient energy transfer was
      observed in dimeric dye 16 in three solvent systems. In contrast, solvent
      dependent energy transfer was detected for another dimeric dye, 5. After close
      investigation, we found that the orientation factor (kappa) is the main factor
      influencing Forster resonance energy transfer in these dyes. 

PMID- 25867284
TI  - Microbial mats as a biological treatment approach for saline wastewaters: the
      case of produced water from hydraulic fracturing.
AB  - Treatment of produced water, i.e. wastewater from hydraulic fracturing, for reuse
      or final disposal is challenged by both high salinity and the presence of organic
      compounds. Organic compounds in produced water may foul physical-chemical
      treatment processes or support microbial corrosion, fouling, and sulfide release.
      Biological approaches have potential applications in produced water treatment,
      including reducing fouling of physical-chemical treatment processes and
      decreasing biological activity during produced water holding; however,
      conventional activated sludge treatments are intolerant of high salinity. In this
      study, a biofilm treatment approach using constructed microbial mats was
      evaluated for biodegradation performance, microbial community structure, and
      metabolic potential in both simulated and real produced water. Results
      demonstrated that engineered microbial mats are active at total dissolved solids
      (TDS) concentrations up to at least 100,000 mg/L, and experiments in real
      produced water showed a biodegradation capacity of 1.45 mg COD/gramwet-day at a
      TDS concentration of 91,351 mg/L. Additionally, microbial community and
      metagenomic analyses revealed an adaptive microbial community that shifted based
      upon the sample being treated and has the metabolic potential to degrade a wide
      array of contaminants, suggesting the potential of this approach to treat
      produced waters with varying composition. 

PMID- 25867285
TI  - Murine typhus in a liver transplant recipient: report of a first case.
AB  - Zoonoses, especially rickettsial diseases, are rarely reported in solid organ
      transplant recipients. We report here a case of murine typhus in a 69-year-old
      liver transplant recipient, who presented with acute febrile illness 5 years post
      transplantation. Although receiving treatment with broad-spectrum antibiotics, he
      was still febrile and developed progressive dyspnea. Laboratory results showed
      elevated transaminases and his chest radiograph revealed bilateral interstitial
      infiltration. The diagnosis of murine typhus was made by a 4-fold rise in
      specific Rickettsia typhi antibody, using indirect immunofluorescent assay. He
      dramatically improved after treatment with doxycycline for 7 days. To our
      knowledge, this is the first case report of murine typhus in a liver transplant
      recipient.

PMID- 25867286
TI  - Transglutaminase 6 Antibodies in the Serum of Patients With Amyotrophic Lateral
      Sclerosis.
AB  - IMPORTANCE: Celiac disease is an autoimmune disorder triggered by gluten in
      genetically predisposed individuals. Gluten sensitivity can cause neurologic
      manifestations, such as ataxia or neuropathy, with or without gastrointestinal
      symptoms. Many patients with gluten ataxia produce antibodies toward the newly
      identified neuronal transglutaminase 6 (TG6). Two case reports described patients
      initially diagnosed with amyotrophic lateral sclerosis (ALS) and ultimately with
      celiac disease who improved with a strict gluten-free diet. OBJECTIVE: To
      evaluate the prevalence of celiac disease-related antibodies and HLA antigen
      alleles, as well as TG6 antibodies, in patients with ALS and healthy individuals
      serving as controls to determine whether a neurologic presentation of a gluten
      related disorder mimicking ALS might occur in some patients. DESIGN, SETTING, AND
      PARTICIPANTS: In a case-control study conducted in an ALS tertiary center, we
      measured serum levels of total IgA antibodies, IgA antibodies to transglutaminase
      2 (TG2) and endomysium, as well as IgA and IgG antibodies to deamidated gliadine
      peptide and TG6 and performed HLA antigen genotyping in 150 consecutive patients
      with ALS and 115 healthy volunteers of similar age and sex. Participants did not
      have any known autoimmune or gastroenterologic disorder and were not receiving
      any immunomodulatory medications. The study was conducted from July 1, 2010, to
      December 31, 2012. MAIN OUTCOMES AND MEASURES: Antibody levels and frequency of
      individuals with abnormal antibody values as well as frequency of HLA antigen
      alleles were compared between patient and control groups. RESULTS: All patients
      and control group participants were seronegative to IgA antibodies to TG2,
      endomysium, and deamidated gliadine peptide. Twenty-three patients (15.3%) were
      seropositive to TG6 IgA antibodies as opposed to only 5 controls (4.3%) (P =
      .004). The patients seropositive for TG6 showed a classic picture of ALS, similar
      to that of seronegative patients. Fifty patients and 20 controls were tested for
      celiac disease-specific HLA antigen alleles; 13 of 22 TG6 IgA seropositive
      individuals (59.1%) were seropositive for celiac disease-related alleles compared
      with 8 (28.6%) of the 28 seronegative individuals (P = .04). Mean (SD) levels of
      IgA antibodies to TG2 were 1.78 (0.73) in patients and 1.58 (0.68) in controls
      (normal, <10). In a subset of study participants, mean levels of deamidated
      gliadin peptide autoantibodies were 7.46 (6.92) in patients and 6.08 (3.90) in
      controls (normal, <16). Mean levels of IgA antibodies to TG6 were 29.3 (30.1) in
      patients and 21.0 (27.4) in controls (P = .02; normal, <26). CONCLUSIONS AND
      RELEVANCE: The data from this study indicate that, in certain cases, an ALS
      syndrome might be associated with autoimmunity and gluten sensitivity. Although
      the data are preliminary and need replication, gluten sensitivity is potentially
      treatable; therefore, this diagnostic challenge should not be overlooked.

PMID- 25867294
TI  - Probing methanol cluster growth by vacuum ultraviolet ionization.
AB  - The ability to probe the formation and growth of clusters is key to answering
      fundamental questions in solvation and nucleation phenomena. Here, we present a
      mass spectrometric study of methanol cluster dynamics to investigate these two
      major processes. The clusters are produced in a molecular beam and ionized by
      vacuum ultraviolet (VUV) radiation at intermediate distances between the nozzle
      and the skimmer sampling different regimes of the supersonic expansion. The
      resulting cluster distribution is studied by time-of-flight mass spectrometry.
      Experimental conditions are optimized to produce intermediate size protonated
      methanol and methanol-water clusters and mass spectra and photoionization onsets
      and obtained. These results demonstrate that intensity distributions vary
      significantly at various nozzle to ionization distances. Ion-molecule reactions
      closer to the nozzle tend to dominate leading to the formation of protonated
      species. The protonated trimer is found to be the most abundant ion at shorter
      distances because of a closed solvation shell, a larger photoionization cross
      section compared to the dimer, and an enhanced neutral tetramer precursor. On the
      other hand, the protonated dimer becomes the most abundant ion at farther
      distances because of low neutral density and an enhanced charged protonated
      monomer-neutral methanol interaction. Thomson's liquid drop model is used to
      qualitatively explain the observed distributions. 

PMID- 25867293
TI  - Protein pheromone expression levels predict and respond to the formation of
      social dominance networks.
AB  - Communication signals are key regulators of social networks and are thought to be
      under selective pressure to honestly reflect social status, including dominance
      status. The odours of dominants and nondominants differentially influence
      behaviour, and identification of the specific pheromones associated with, and
      predictive of, dominance status is essential for understanding the mechanisms of
      network formation and maintenance. In mice, major urinary proteins (MUPs) are
      excreted in extraordinary large quantities and expression level has been
      hypothesized to provide an honest signal of dominance status. Here, we evaluate
      whether MUPs are associated with dominance in wild-derived mice by analysing
      expression levels before, during and after competition for reproductive resources
      over 3 days. During competition, dominant males have 24% greater urinary MUP
      expression than nondominants. The MUP darcin, a pheromone that stimulates female
      attraction, is predictive of dominance status: dominant males have higher darcin
      expression before competition. Dominants also have a higher ratio of darcin to
      other MUPs before and during competition. These differences appear transient,
      because there are no differences in MUPs or darcin after competition. We also
      find MUP expression is affected by sire dominance status: socially naive sons of
      dominant males have lower MUP expression, but this apparent repression is
      released during competition. A requisite condition for the evolution of
      communication signals is honesty, and we provide novel insight into pheromones
      and social networks by showing that MUP and darcin expression is a reliable
      signal of dominance status, a primary determinant of male fitness in many
      species.

PMID- 25867295
TI  - Methoxetamine: An early report on the motivations for use, effect profile and
      prevalence of use in a UK clubbing sample.
AB  - INTRODUCTION AND AIMS: To assess the prevalence of use and subjective effect
      profile of methoxetamine among a group of polydrug users. DESIGN AND METHODS:
      Cross-sectional, anonymous, online survey of UK-based polydrug users was
      conducted. Prevalence of lifetime, last year and last month use, sourcing of the
      drugs, motivations for use, and subjective effect and risk profile compared with
      that of ketamine were measured. RESULTS: There were 7700 UK-based polydrug users,
      of whom 326 reported recent use of methoxetamine. Of the whole sample, 4.2%
      reported last 12 month use of methoxetamine compared with 24.5% for ketamine. The
      most common route of use was intranasal and the predominate effect described as
      psychedelic. Of the 15.5% of last year users of ketamine reporting last year use
      of methoxetamine, only 18.7% reported that they thought methoxetamine was less
      damaging to their kidneys or bladder than ketamine. Its broad effect profile,
      based on participants' first experience of use, was very similar to that of
      ketamine. Almost one-third of users reported that they did not intend to try the
      drug again. DISCUSSION AND CONCLUSIONS: Methoxetamine appears to have a broadly
      similar effect profile to that of ketamine. Only a minority of participants were
      motivated to use it because they believed it was less damaging to their kidneys
      or bladder than ketamine. The impact of the recent temporary banning order on
      availability and use of both methoxetamine and ketamine should be monitored
      carefully.

PMID- 25867296
TI  - Successful use of therapeutic hypothermia after cardiac arrest due to
      amitriptyline and venlafaxine intoxication.
AB  - The prognosis of out-of-hospital cardiac arrest (OHCA) due to intoxication is
      dismal. Tricyclic antidepressants (TCAs) are widely used in the treatment of
      depression, but possess significant cardiotoxicity, and are one of the most
      common medications used in suicide attempts worldwide. TCA poisoning can cause
      hypotension, seizures, and cardiac conduction disturbances, which can lead to
      life-threatening arrhythmia. Current guidelines recommend mild therapeutic
      hypothermia (TH) for unconscious survivors of OHCA, but hypothermia treatment
      itself can cause disturbances in cardiac conduction, which could aggravate the
      effect of TCAs on cardiac conduction. We report the successful use of TH in a 19
      year-old woman who was resuscitated from ventricular tachycardia after
      intentional ingestion of amitriptyline and venlafaxine, a serotonin
      norepinephrine reuptake inhibitor. The cardiac arrest was witnessed, but no
      bystander cardiopulmonary resuscitation (CPR) was performed. The initial rhythm
      was ventricular tachycardia with no detectable pulse. Three defibrillations,
      magnesium sulfate, and sodium bicarbonate were given and her trachea was
      intubated, after which return of spontaneous circulation (ROSC) was achieved in
      26 minutes. After ROSC, she had seizures and was sedated with propofol. Out-of
      hospital TH was initiated with 1500 mL of cold Ringer's acetate. An infusion of
      norepinephrine was initiated for low blood pressure. On arrival at the university
      hospital, she was unconscious and had dilated pupils. She was tachycardic with a
      body temperature of 33.5 degrees C. She was transferred to the intensive care
      unit and TH was maintained with invasive cooling. During the TH treatment, she
      did not experience any serious cardiac arrhythmia, transthoracic echocardiogram
      was normal, and the electrocardiogram (ECG) returned to normal. The patient was
      extubated 45 hours after the cardiac arrest. After the extubation, she was alert
      and cooperative, but slightly delusional. She was transferred to a ward on the
      third day and discharged from hospital on the sixth day of admission. Ambulatory
      psychiatric follow-up was organized. Neuropsychological examinations were later
      performed and she was estimated to be able to work at her previous job. This case
      report suggests that mild TH is safe even in case of intoxication with a drug
      known to cause serious cardiac conduction disturbances and arrhythmia.

PMID- 25867297
TI  - Analysis of genetic diversity of the heat shock protein 70 gene on the basis of
      abundant sequence polymorphisms in chicken breeds.
AB  - This study was designed to detect the sequence variation of the chicken heat
      shock protein 70 (HSP70) gene. A total of 102 individuals from 8 native Chinese
      breeds together with Dwarf White Chicken and Red Junglefowl were used to detect
      sequence variations. The coding regions of the chicken HSP70 gene from 102
      individuals were cloned and sequenced. Thirty-six variations were identified,
      which included 34 single nucleotide polymorphisms and 2 indel mutations. Fifty
      seven haplotypes were observed, of which, 43 were breed-specific and 14 were
      shared. There were 7 Red Junglefowl-specific haplotypes, while Haidong and Silkie
      only had 2 specific haplotypes. Eleven and 3 haplotypes were shared between and
      within species, respectively. The variation in nucleotide diversity (Pi) and
      average number of nucleotide differences (K) among species were consistent. The
      total Pi of HSP70 was 0.0016, and the total K was 4.1998. The Pi value of Red
      Junglefowl was the highest (0.0018) and K was 4.8000, while the Pi of Silkie was
      the lowest (0.0010) and K was 2.5000. These results demonstrated that variation
      in chicken HSP70 was abundant between and within species. 

PMID- 25867298
TI  - Treatment of vertebral body compression fractures using percutaneous kyphoplasty
      guided by a combination of computed tomography and C-arm fluoroscopy with finger
      touch guidance to determine the needle entry point.
AB  - This study aimed to evaluate the results and complications of image-guided
      percutaneous kyphoplasty (PKP) using computed tomography (CT) and C-arm
      fluoroscopy, with finger-touch guidance to determine the needle entry point. Of
      the 86 patients (106 PKP) examined, 56 were treated for osteoporotic vertebral
      compression fractures and 30 for vertebral tumors. All patients underwent image
      guided treatment using CT and conventional fluoroscopy, with finger-touch
      identification of a puncture point within a small incision (1.5 to 2 cm). Partial
      or complete pain relief was achieved in 98% of patients within 24 h of treatment.
      Moreover, a significant improvement in functional mobility and reduction in
      analgesic use was observed. CT allowed the detection of cement leakage in 20.7%
      of the interventions. No bone cement leakages with neurologic symptoms were
      noted. All work channels were made only once, and bone cement was distributed
      near the center of the vertebral body. Our study confirms the efficacy of PKP
      treatment in osteoporotic and oncological patients. The combination of CT and C
      arm fluoroscopy with finger-touch guidance reduces the risk of complications
      compared with conventional fluoroscopy alone, facilitates the detection of minor
      cement leakage, improves the operative procedure, and results in a favorable bone
      cement distribution. 

PMID- 25867299
TI  - Heterozygosities and genetic relationship of tea cultivars revealed by simple
      sequence repeat markers and implications for breeding and genetic mapping
      programs.
AB  - Genetic maps are essential tools for quantitative trait locus analysis and marker
      assisted selection breeding. In order to select parents that are highly
      heterozygous for genetic mapping, the heterozygosity (HS) of 24 tea cultivars
      (Camellia sinensis) was analyzed with 72 simple sequence repeat markers. In
      total, 359 alleles were obtained with an average of 4.99 per marker. The HS
      varied greatly from 37.5 to 71.0% with an average of 51.3%. On average, tea
      cultivars from Fujian Province showed a higher level of heterozygosity (59.8%)
      than those from Zhejiang (48.5%) and Yunnan (44.5%), and the 12 national tea
      cultivars were generally more heterozygous than the 12 provincial cultivars.
      Unweighted pair-group analysis using the arithmetic average grouping divided the
      24 cultivars into 2 groups that are consistent with the morphological
      classification. All dual combinations of the 24 cultivars were studied to
      calculate the percentage of mappable markers when using pseudo-testcross mapping
      strategy, and results showed that this value also varied greatly from 51.4 to
      90.3%. The genetic relationships and HS differences among different cultivars
      were discussed, and tea cultivars with high HS were recommended as cross parents
      for genetic mapping programs.

PMID- 25867300
TI  - Association between the C804A polymorphism in the TGF-beta gene and the risk of
      myocardial infarction: a meta-analysis.
AB  - Tumor necrosis factor-beta (TNF-beta) is an important mediator of inflammation
      and may play a role in the pathogenesis of myocardial infarction (MI). While
      several published studies have investigated the association between the C804A
      polymorphism in the TNF-beta gene and MI risk, their results are controversial
      and ambiguous. In this study, we evaluated the contribution of the TNF-beta C804A
      polymorphism to MI risk. A literature search was conducted in the PubMed, Embase,
      Web of Science, Cochrane Library, and Google Scholar databases to identify
      eligible studies published before November 1, 2013. We performed a meta-analysis
      of 9 case-control studies, which included a total of 19,404 MI patients and
      13,684 healthy controls. Overall analysis suggested that the TNF-beta C804A
      polymorphism was associated with a significantly increased risk of MI. Stratified
      analysis based on ethnicity revealed a significant association in Asian
      populations, but not in Caucasian populations. In conclusion, this meta-analysis
      revealed that the TNF-beta C804A polymorphism may be associated with an increased
      risk of MI only in Asian populations. However, additional studies should be
      conducted to further confirm the association between TNF-beta C804A and MI risk. 

PMID- 25867301
TI  - Androgen receptor gene CAG repeat polymorphism and risk of isolated hypospadias:
      results from a meta-analysis.
AB  - Studies investigating the association between the CAG repeat polymorphism and the
      risk of isolated hypospadias have reported conflicting results. The aim of this
      study was to quantitatively summarize the evidence for such a relationship. Two
      investigators independently searched the Medline, Embase, CNKI, and Wanfang
      databases. Weighted mean difference and 95% confidence intervals for the CAG
      repeat polymorphism and isolated hypospadias were calculated using a random
      effects model. Subgroup analyses were performed by race, study design, sample for
      DNA extraction, and hypospadias classifications. This meta-analysis included 6
      case-control studies, including 444 isolated hypospadias cases and 727 controls.
      The results showed that patients with isolated hypospadias had longer CAG repeats
      in their androgen receptor gene sequence (weighted mean difference = 1.36, 95%
      confidence interval = 0.60-2.13; P = 0.0005). Similarly, stratified analyses also
      detected significant associations in all subgroups, excluding the group with
      severe hypospadias (weighted mean difference = 0.35, 95% confidence interval = 
      0.42-1.12; P = 0.38). This meta-analysis indicated that longer CAG repeats were
      associated with the risk of isolated hypospadias, and that longer CAG
      polymorphisms may be related to the etiology of isolated hypospadias. Future
      studies based on Asian and African-American patients should be performed to re
      evaluate this association. 

PMID- 25867302
TI  - Gene expression, serum amino acid levels, and growth performance of pigs fed
      dietary leucine and lysine at different ratios.
AB  - We examined 96 pigs (28.1 +/- 0.83 kg) to analyze the effect of Leu:Lys ratios on
      expression of the cationic amino acid transporters b(0,+) and CAT-1 in the
      jejunum and liver as well as myosin expression in 2 muscles to estimate the
      optimum standardized ileal digestible (SID) Leu:Lys ratio for growth rate and
      efficiency. A wheat-and wheat bran-based diets were formulated to meet the
      requirements of SID amino acids other than Leu (0.70%) and Lys (0.80%). L-Leu was
      added to the basal diet in 5 SID Leu:Lys ratios (88, 100, 120, 140, and 160% in
      diets 1-5). Tissue samples were collected from 8 pigs with ratios of 88, 120, and
      160%. Relative expression of b(0,+), CAT-1, and myosin was analyzed. b(0,+)
      expression in the jejunum was higher but lower in the liver of pigs with the 120%
      ratio compared to those with the 88 or 160% ratio; myosin expression in
      longissimus dorsi was also higher in pigs with the 120% ratio (P < 0.05). CAT-1
      was lower in the jejunum and longissimus dorsi of pigs with 120 or 160% ratios
      than in pigs with 88%. Serum concentration of nearly all amino acids decreased
      with excess dietary Leu (P < 0.05). The SID Leu:Lys of 104 and 109% optimized
      average daily gain and feed conversion ratio, respectively. Thus, the dietary
      Leu:Lys ratio affects the expression of genes coding for amino acid transporters
      and myosin, the availability of Lys, and the growth rate and efficiency in pigs. 

PMID- 25867303
TI  - Analysis of microbial diversity and niche in rhizosphere soil of healthy and
      diseased cotton at the flowering stage in southern Xinjiang.
AB  - Understanding how microbial community composition and diversity respond to
      continuous cropping obstacle is not well understood. However, determining the
      community composition vs assessing the diversity of molecular operational
      taxonomic units is often difficult. In this study, we focused on the microbial
      diversity and niche differentiation in rhizosphere soils between healthy and
      diseased cotton using a molecular approach based on a culture-independent method.
      A total of 124 operational taxonomic units (OTUs) from 1076 DNA fragments were
      detected, including 46, 57, and 21 OTUs from fungi, bacteria, and actinomycetes,
      respectively. The identified OTUs were confirmed by sequencing after polymerase
      chain reaction-restriction fragment length polymorphism analysis. The number of
      OTUs from Fusarium species in diseased rhizosphere soils was higher than that in
      healthy rhizosphere, which was consistent with field observations. Overall, the
      results showed that microbes in healthy rhizosphere soils were more diverse and
      occupied a wider niche in the healthy rhizosphere soil environment of the cotton
      field. Beneficial microbes should further be analyzed in studies examining the
      soil ecology of fields in which continuous cropping of cotton takes place. 

PMID- 25867304
TI  - Epidemiological analysis of pneumoconiosis in the Xinjiang Uygur Autonomous
      Region and cases reported by the Urumqi Railway Bureau.
AB  - This study investigated the incidence and development of pneumoconiosis in the
      Xinjiang Uygur Autonomous Region and cases reported by the Urumqi Railway Bureau
      to provide a scientific basis for developing prevention and control measures
      against pneumoconiosis. Data from pneumoconiosis cases were input into Excel and
      analyzed by SPSS version 17.0. There were 13,165 cases of pneumoconiosis through
      2010. Coal workers accounted for the largest proportion of cases. From July 2006
      through 2010, a total of 1233 new cases of pneumoconiosis were reported in the
      Xinjiang Uygur Autonomous Region; most cases were reported in Urumqi. From 1981
      to 2012, 3332 new cases of pneumoconiosis had been confirmed by the Urumqi
      Railway Bureau, including 77.73, 16.96, and 5.31% stage I, II, and III cases,
      respectively. In the last 30 years, the number of new pneumoconiosis cases peaked
      in 1986; most of them were silicosis cases. In addition, there were more than 200
      cases of pneumoconiosis combined with pulmonary tuberculosis reported by the
      Urumqi Railway Bureau. The coal industry in Urumqi is the main industry in which
      occupational pneumoconiosis occurs in Xinjiang. Thus, substantial effort is still
      required to eliminate pneumoconiosis by 2030.

PMID- 25867305
TI  - Genetic diversity of Qatari date palm using SSR markers.
AB  - The genetic diversity in the date palm germplasm of 59 female accessions
      representing 12 cultivars from different locations in Qatar was investigated
      using 14 loci of simple-sequence repeat (SSR) primers. A total of 94 alleles,
      with a mean of 6.7 alleles per locus, were scored. The number of alleles per
      locus varied from 3 (primer mPdCIR090) to 11 (primers mPdCIR010 and mPdCIR015).
      The amplified SSR band sizes ranged from 104 to 330 bp. The mean gene diversity
      was 0.66 and ranged from 0.39 (locus mPdCIRO93) to 0.86 (locus mPdCIR015),
      indicating that the Qatari date palm collection has a high degree of genetic
      diversity. The heterozygosity ranged from 0 (marker mPdCIR090) to 98% (marker
      mPdCIR010). Forty-four percent of the variability is explained at the inter
      population level, while 56% of the variability is maintained within individuals.
      However, the loci mPdCIR044, mPdCIR057, mPdCIR090, and mPdCIR093 revealed that
      the total gene diversity is explained at the inter-population level. The Qatari
      populations Khalas, Shishi, Barhi, Hillali, Khnaizi, Gar, and Jabri showed
      significant differentiation compared to all other populations. The average
      fixation index was 0.24814, showing that about 24.81% of the genetic variation
      was present among populations, which correlated with analysis of molecular
      variance.

PMID- 25867306
TI  - Mapping quantitative trait loci for sheath blight disease resistance in Yangdao 4
      rice.
AB  - Rice sheath blight (ShB), which is caused by Rhizoctonia solani, has become the
      most serious rice disease in China. Yangdao 4, a cultivar with partial resistance
      to ShB, was crossed with Lemont, a susceptible cultivar, to develop mapping
      populations that were used to analyze quantitative trait loci (QTL) that confer
      resistance to ShB. QTL analysis were performed in 3 environments (E1-E3) using 2
      F2 and 1 F2:3 populations, respectively. Three traits were recorded to evaluate
      ShB resistance, including disease rating (DR), lesion height (LH), and percentage
      of lesion height (PLH). Based on field evaluation of ShB resistance and the 2
      genetic maps constructed, we identified a total of 8 QTLs for DR (4 in E1, 4 in
      E2, and 3 in E3), 6 QTLs for LH (1 in E1, 3 in E2, and 2 in E3), and 7 QTLs for
      PLH (1 in E1, 4 in E2, and 2 in E3). Sixteen of the ShB-QTLs co-localized as 6
      clusters on chromosomes 3, 7, 11, and 12. Four of the 6 clusters contained ShB
      QTLs that were detected in 2 environments, while the other 2 clusters with ShB
      QTLs were detected in 1 environment. Three ShB-QTLs (qSBD-3-2, qSBL-3-1, and
      qSBPL-3-1) were delimited to a 581-kb region flanked by markers D333B and D334 on
      chromosome 3. The resistance alleles of Yangdao 4 at the qSBD-3-2 locus decreased
      DR by 0.68 and 0.79 in E2 and E3, respectively.

PMID- 25867307
TI  - A novel random amplified polymorphic DNA-based strategy for genetic diversity
      analysis and identification of tomatoes.
AB  - Cultivar identification diagrams (CIDs) provide a rapid and efficient approach
      for identifying cultivars based on random amplified polymorphic DNA (RAPD)
      markers. In this paper, 64 tomato cultivars were identified using a CID. Using
      RAPD profiles, clustering analysis was performed to analyze genetic diversity.
      The results showed that 8 RAPD primers could completely separate the 64 cultivars
      according to the obtained polymorphic bands; a CID of the 64 tomato cultivars was
      then constructed. As verification of the CID validity, 8 randomly selected
      cultivars were investigated and proven to be well distinguished. In addition, 33
      DNA bands were obtained, 20 (60.6%) of which were polymorphic. Genetic distances
      were calculated with a range of 0.032 to 1.402. Clustering analysis showed that
      the 64 tomato cultivars were divided into 4 groups with a similarity coefficient
      of 0.40. Using this novel strategy, with the same RAPD data, both CID and
      clustering analysis can simultaneously determine tomato cultivars and their
      genetic diversity. 

PMID- 25867308
TI  - Quantitative changes in mitochondrial DNA copy number in various tissues of pigs
      during growth.
AB  - Mitochondrial DNA (mtDNA) content is dependent on the energy requirements of
      tissues. To date, no comprehensive study has been conducted to examine mtDNA copy
      number variations in pigs. In the current study, quantitative polymerase chain
      reaction was performed to quantify the mtDNA copy number in 15 pig tissue types
      at 5 growth stages from embryo to adult. Observable differences in mtDNA content
      were detected in the tissues, including a 6-fold greater mtDNA content in the
      heart compared with the lung of 180-day-old samples. mtDNA content in the heart,
      longissimus dorsi muscle, psoas major muscle, kidney, brain, ovary, and
      subcutaneous adipose increased with growth. Expression of the replicative
      mitochondrial helicase (TWINKLE), which regulates mtDNA turnover, was
      significantly associated with changes in mtDNA copy numbers across tissues during
      growth (r = 0.33, P = 0.01). We demonstrated that the expression levels of
      mitochondrial genes were positively correlated with mtDNA copy number. 

PMID- 25867309
TI  - Influence of sugars and hormones on the genes involved in sucrose metabolism in
      maize endosperms.
AB  - Starch is the major storage product in the endosperm of cereals. Its synthesis is
      closely related to sucrose metabolism. In our previous study, we found that the
      expression of most of the genes involved in starch synthesis might be regulated
      by sugars and hormones in the maize endosperm. However, little is known regarding
      the transcriptional regulation of genes involved in sucrose metabolism. Thus, in
      this study, maize endosperms were treated with different sugars and hormones and
      the expression of genes involved in sucrose metabolism (including synthesis,
      degradation, and transport) were evaluated using real-time quantitative reverse
      transcription-polymerase chain reaction. We found that genes affected by
      different sugars and hormones were primarily regulated by abscisic acid. Sucrose
      and abscisic acid showed an additive effect on the expression of some genes.
      Differences in the transcriptional regulation of genes involved in sucrose
      metabolism and starch biosynthesis were observed. 

PMID- 25867311
TI  - Postnatal diagnosis of constitutive ring chromosome 13 using both conventional
      and molecular cytogenetic approaches.
AB  - We describe the first postnatal diagnosis of a child from Central Brazil with de
      novo cytogenetic alterations in 13q showing malformations of the brain, eyes,
      distal limbs, and genitourinary tract, and severe intellectual disability. The
      karyotype was a constitutive 46,XX,r(13)[77]/45,XX,-13[17]/46,XX,idic r(13)[6].
      Interphase and metaphase fluorescence in situ hybridization analyses also showed
      the absence of 13qter and the presence of 13q14.3 in the cells with r(13), and
      chromosome microarray analysis detected a 15.39 Mb deletion in chromosome region
      13q32.3-q34. This study is intended as the registry of a rare case of chromosomal
      rearrangement involving chromosome 13 in Central Brazil. Further studies are
      needed to define whether genetic haploinsufficiency is associated with each major
      13q deletion anomaly. 

PMID- 25867310
TI  - Resistant starch: a functional food that prevents DNA damage and chemical
      carcinogenesis.
AB  - Resistant starch is formed from starch and its degradation products and is not
      digested or absorbed in the intestine; thus, it is characterized as a fiber.
      Because fiber intake is associated with the prevention of DNA damage and cancer,
      the potential antigenotoxic, antimutagenic, and anticarcinogenic capabilities of
      resistant starch from green banana flour were evaluated. Animals were treated
      with 1,2-dimethylhydrazine and their diet was supplemented with 10% green banana
      flour according to the following resistant starch protocols: pretreatment,
      simultaneous treatment, post-treatment, and pre + continuous treatment. The
      results demonstrated that resistant starch is not genotoxic, mutagenic, or
      carcinogenic. The results suggest that resistant starch acts through
      desmutagenesis and bio-antimutagenesis, as well as by reducing aberrant crypt
      foci, thereby improving disease prognosis. These findings imply that green banana
      flour has therapeutic properties that should be explored for human dietary
      applications. 

PMID- 25867312
TI  - Expression and hypoxia adaptation analysis of the EPO gene in different tissues
      of plateau Tibetan pigs.
AB  - This study aimed to observe the expression characteristics of the erythropoietin
      (EPO) gene in different tissues of Tibetan pigs and to explore the adaptation to
      hypoxic environments. The cDNA in heart, liver, lung, kidney, muscle, brain, and
      fat of Tibetan pigs was used as the template. Through the number of cycles of the
      polymerase chain reaction (PCR), annealing temperature, and system optimization,
      a stable and specific semi-quantitative PCR system was established. The EPO gene
      in different tissues of Tibetan pigs was detected using this system. The results
      showed that the EPO gene was expressed in heart, liver, lung, kidney, muscle,
      brain, and fat of the pigs. There were obvious differences in the expression in
      each tissue, and the expression sequence was as follows: kidney > muscle > lung >
      brain > liver > heart > fat. The results showed that the EPO gene was expressed
      in various tissues of Tibetan pigs. There were obvious differences in expression
      and each tissue may play a different regulatory role in the adaptation to
      hypoxia. 

PMID- 25867313
TI  - Effects of angiotensin II intervention on MMP-2, MMP-9, TIMP-1, and collagen
      expression in rats with pulmonary hypertension.
AB  - This study investigated the effects of angiotensin II (AngII) intervention, using
      captopril and losartan, on the expression of matrix metalloproteinase-2 (MMP-2),
      MMP-9, tissue inhibitor of metalloproteinase-1 (TIMP-1), and collagen in rats
      with pulmonary hypertension, in an effort to understand mechanisms underlying
      pulmonary vascular remodeling. A total of 40 male Sprague-Dawley rats were
      randomly divided into normal group, model group, captopril group, and losartan
      group. After 5 weeks, the mean pulmonary arterial pressure (mPAP), right
      ventricular index, and neointima formation in each group were determined.
      Immunohistochemical analysis was performed to determine the degree of pulmonary
      arterial muscularization as well as MMP-2, MMP-9, and TIMP-1 protein expression
      in lung tissue. Real-time fluorescent quantitative PCR was used to detect MMP2,
      MMP9, TIMP1, COL1A1, and COL4A1 mRNA expression. Picro-sirius red staining was
      performed to detect collagen protein expression. Neointima formation was observed
      in the model group. Moreover, the mPAP, right ventricular index, degree of
      arterial muscularization, and collagen deposition, as well as mRNA and protein
      expression of MMP2, MMP9, and TIMP1 were significantly higher than those in the
      other groups (P < 0.05). The mPAP, right ventricular index, degree of arterial
      muscularization, and mRNA and protein expression in the captopril and losartan
      groups were significantly decreased compared with those of the model group (P <
      0.05). AngII regulates MMP-2, MMP-9, and TIMP-1 expression and affects collagen
      deposition. Thus, this hormone is involved in pulmonary vascular remodeling,
      indicating a possible mechanism that can be targeted in pulmonary hypertension
      intervention. 

PMID- 25867314
TI  - Genetic analysis of STR markers on chromosome 21 in a Han population from
      southeast China.
AB  - Short tandem repeats (STRs) are highly polymorphic sequences and have been
      extensively used as genetic markers in mapping studies, disease diagnosis, and
      human identity testing. In this study, 11 STR markers on chromosome 21, including
      D21S1432, D21S11, D21S1246, D21S1412, D21S1437, D21S1442, D21S2039, D21S1270,
      D21S1435, D21S1409, and D21S1446, were analyzed in 740 unrelated Han individuals
      from southeast China. A total of 132 alleles, ranging from 7-21 for each locus,
      were named according to the guidelines of the International Society for Forensic
      Haemogenetics. The distributions of allelic frequencies for the 11 STRs and
      population genetic parameters were determined. All 11 STR markers showed high
      polymorphism and heterogeneity in the southeast Han population, with polymorphism
      information content of 0.61-0.87, heterogeneity of 64.5-86.1%, and power of
      discrimination of 0.835-0.973. Among the 11 STR markers, D21S1412, D21S1270,
      D21S11, and D21S1442 showed relatively higher heterogeneity. Their combination
      was relatively informative and was used in a quantitative fluorescence-polymerase
      chain reaction assay to diagnose Down syndrome (trisomy 21) in a southeast
      Chinese Han population. The genetic information and population data for these 11
      STRs may be used not only in quantitative fluorescence-polymerase chain reaction
      assays but also in forensic studies and other genetic tests.

PMID- 25867315
TI  - Clinical value of fluid bolus contrast flow meter during hysterosalpingography.
AB  - The purpose of this study was to investigate the clinical value of the fluid
      bolus contrast flow meter during hysterosalpingography. Hysterosalpingography
      information of 342 cases, which included a manual handset group of 213 cases and
      a bolus instrument group of 129 cases were reviewed. Comparative analysis was
      used to compare the two groups in order to assess the clinical adverse reactions,
      contrast agent reflux, and image quality. In the instrument bolus group compared
      with the manual handset group, the clinical adverse reactions decreased from
      75.12 to 31.78% (P < 0.001); the backflow phenomenon of the contrast agent
      decreased from 13.62 to 3.10% (P < 0.01); and image quality significantly
      improved, with the A class film rate increasing from 54.46 to 68.99% (P < 0.01)
      and the C class film rate decreasing from 8.92 to 2.33% (P < 0.05). The use of a
      contrast bolus through the liquid inlet of the hysterosalpingography instrument
      can provide fully dynamic observation, reducing the contrast agent reflux and
      adverse reactions as well as improving the image quality and diagnostic accuracy.
      In addition, the medical staff is not subjected to radiographic radiation.
      Therefore, it is a safe and reliable imaging method. 

PMID- 25867316
TI  - Correlation analysis of the PNPLA7 gene polymorphism and susceptibility to
      menstrual disorder.
AB  - We examined the correlation between PNPLA7 gene polymorphisms at the rs61754920
      and rs11137410 loci and menstrual disorder in women of reproductive age in the
      Central Plain. Genomic DNA was extracted from peripheral blood; polymerase chain
      reaction-ligase detection reaction and SNaPshot genotyping were used to detect
      polymorphisms in the rs61754920 and rs11137410 gene loci, respectively. The
      results for the 2 loci in individuals of different blood types were statistically
      analyzed. The proportion of the AA homozygote at the rs61754920 locus in the
      PNPLA7 gene was the lowest, while the proportion of the CC homozygote at the
      rs11137410 locus in the PNPLA7 gene was the highest. There were no statistical
      differences in the frequency distribution of genotypes and alleles at the 2 loci
      between control and test groups. The frequency of the TT genotype at the
      rs11137410 locus in women with type O blood was significantly lower in the test
      group than in the control group. Frequencies of the C and T alleles were
      significantly different between the 2 groups. There may be an association between
      the PNPLA7 gene and type O blood or a combined effect of the 2 genes. 

PMID- 25867317
TI  - Association between the FGB gene polymorphism and ischemic stroke: a meta
      analysis.
AB  - To clarify the relationship between the beta-fibrinogen (FGB) genetic
      polymorphism (-148C>T) and ischemic stroke, we identified studies by searching
      PubMed, EMBASE, and the Chinese National Knowledge Infrastructure (CKNI)
      databases. Data from eligible studies were extracted and subjected to meta
      analysis. Publication bias was tested using a funnel plot. We identified 12
      independent case-control studies containing 1536 ischemic stroke patients and
      1329 control subjects. Our results showed that the -148C>T polymorphism in the
      FGB gene was associated with an increased risk of ischemic stroke [CC vs (TT+CT),
      odds ratio = 0.69, 95% confidence interval (CI) = 0.59-0.80, P < 0.0001; TT vs
      (CC+CT), odds ratio = 3.01, 95%CI = 1.29-7.05; P = 0.01; T vs C, odds ratio =
      1.32, 95%CI = 1.15-1.52, P < 0.0001] by a meta-analysis. The results of our meta
      analysis suggested that the -148C>T polymorphism in the FGB gene is a
      susceptibility marker of ischemic stroke. 

PMID- 25867318
TI  - Assessment of genetic diversity of bermudagrass germplasm from southwest China
      and Africa by using AFLP markers.
AB  - Cynodon dactylon (L.) Pers. var. dactylon (common bermudagrass) is widely
      distributed geographically between approximately 45 degrees N and 45 degrees S
      latitude, penetrating to approximately 53 degrees N latitude in Europe. The
      extensive variation of morphological and adaptive characteristics of the taxon
      has been substantially documented, but information is lacking on DNA molecular
      variation in geographically disparate forms. The genetic diversity of 51 wild
      accessions of bermudagrass from southwest China (Sichuan, Chongqing, Yunnan,
      Guizhou, and Tibet) and 8 African bermudagrass was analyzed using amplified
      fragment length polymorphism molecular markers. A total of 670 polymorphic bands
      were detected with 11 primer combinations, of which 663 (98.74%) bands were found
      to be polymorphic. The genetic similarity among the accessions ranged from 0.64
      0.96 with an average of 0.78. All 59 wild accessions were clustered into 5 eco
      geographic groups, and nearly all accessions from the same area were classified
      into the same group and were found to be associated with their geographical
      distributions. Therefore, complex geographical and ecological environments are
      important factors for the genetic structure and geographical distribution of C.
      dactylon. 

PMID- 25867319
TI  - Association between the LXRalpha polymorphism and stroke in a Chinese population.
AB  - We examined the relationship between the liver X receptor alpha gene (LXRalpha)
      polymorphism and the susceptibility to stroke. We utilized the single fluorescent
      labeled probe technique to detect the genotype of rs12221497 in the LXRalpha gene
      in 400 stroke patients and 400 healthy control subjects. The difference in
      genotype distribution between the 2 groups was analyzed using the chi-square
      test. Serum lipids and glucose levels between the different genotypes were also
      compared. We found that the risk of stroke in carriers with the AA + GA genotype
      was 2.02-fold higher than that in GG genotype carriers (odds ratio = 2.02, 95%
      confidence interval = 1.18-2.87, P < 0.05), and that the risk of stroke in
      carriers with the A allele increased by 0.606-fold compared to that in G allele
      carriers (odds ratio = 1.606, 95% confidence interval = 1.158-2.228). Logistic
      regression analysis showed that after adjusting for other confounding factors,
      the A allele was an independent risk for stroke. However, there were no
      differences in serum lipids and glucose levels between each genotype. We conclude
      that the rs12221497 polymorphism in the LXRalpha gene was associated with the
      susceptibility to stroke in a Han Chinese population.

PMID- 25867320
TI  - Genetic diversity and classification of Tibetan yak populations based on the
      mtDNA COIII gene.
AB  - To determine the level of genetic diversity and phylogenetic relationships among
      Tibetan yak populations, the mitochondrial DNA cytochrome c oxidase subunit 3
      (COIII) genes of 378 yak individuals from 16 populations were analyzed in this
      study. The results showed that the length of cytochrome c oxidase subunit 3 gene
      sequences was 781 bp, with nucleotide frequencies of 29.2, 29.4, 26.1, and 15.2%
      for T, C, A, and G, respectively. A total of 26 haplotypes were identified, with
      69 polymorphic sites, including 11 parsimony-informative sites and 58 single
      nucleotide polymorphism sites. No deletions/insertions were found in sequence
      comparison, indicating that nucleotide mutation types were transitions and
      transversions. Haplotype and nucleotide diversities were 0.562 and 0.00138,
      respectively, indicating a high level of genetic diversity in Tibetan yak
      populations. Phylogenetic relationship analysis indicated that Tibetan yak
      populations are divided into 2 groups. 

PMID- 25867321
TI  - Optimization of solid-state fermentation conditions for Trichoderma harzianum
      using an orthogonal test.
AB  - The aim of this study was to develop a protocol for the production of fungal bio
      pesticides with high efficiency, low cost, and non-polluting fermentation, while
      also increasing their survival rate under field conditions. This is the first
      study to develop biocontrol Trichoderma harzianum transformants TS1 that are
      resistant to benzimidazole fungicides. Agricultural corn stover and wheat bran
      waste were used as a medium and inducing carbon source for solid fermentation.
      Spore production was observed, and the method was optimized using single-factor
      tests with 4 factors at 3 levels in an orthogonal experimental design to
      determine the optimal culture conditions for T. harzianum TS1. In this step, we
      determined the best conditions for fermenting the biocontrol fungi. The optimal
      culture conditions for T. harzianum TS1 were cultivated for 8 days, a ratio of
      straw to wheat bran of 1:3, ammonium persulfate as the nitrogen source, and a
      water content of 30 mL. Under optimal culture conditions, the sporulation of T.
      harzianum TS1 reached 1.49 x 10(10) CFU/g, which was 1.46-fold higher than that
      achieved before optimization. Increased sporulation of T. harzianum TS1 results
      in better utilization of space and nutrients to achieve control of plant
      pathogens. This method allows for the recycling of agricultural waste straw. 

PMID- 25867322
TI  - C-erbB-2 expression and prognosis of gastric cancer: a meta-analysis.
AB  - The prognostic role of c-erbB-2 in gastric cancer is controversial. We conducted
      a meta-analysis to evaluate the relationship between c-erbB-2 expression and the
      prognosis of gastric cancer. We evaluated 20 published studies assessing the
      relationship between c-erbB-2 and gastric cancer prognosis. The Revman 5.0
      software was used to perform literature retrieval, article selection, data
      collection, and statistical analysis. We utilized a fixed-effect model to pool
      hazard ratios and 95% confidence intervals from the studies. A total of 20
      eligible studies including 4468 gastric cancer patients were analyzed. We were
      unable to demonstrate the prognostic value of c-erbB-2 for gastric cancer (hazard
      ratio = 1.01, 95% confidence interval = 0.87-1.16, P = 0.93). The present study
      indicated that c-erbB-2 expression is not a prognostic factor for gastric cancer.

PMID- 25867323
TI  - Selecting representative microsatellite loci for genetic monitoring and analyzing
      genetic structure of an outbred population of orange tabby cats in China.
AB  - We optimized a panel of microsatellite markers from cat and tiger genetic data
      for efficient genetic monitoring and used it to analyze the genetic structure of
      an outbred cat stock in China. We selected a set of rich polymorphic
      microsatellite loci from 131 cat microsatellite loci and 3 Sumatran tiger
      microsatellite loci using agarose gel electrophoresis. Next, the set of optimized
      genetic markers was used to analyze the genetic variation in an outbred
      population of orange tabby cats in China by simple-tandem repeat scanning. Thirty
      one loci rich in polymorphisms were selected and the highest allele number in a
      single locus was 8. Analysis of the orange tabby cat population illustrated that
      the average observed number of alleles, mean effective allele number, mean
      Shannon's information index, mean expected heterozygosity, and observed
      heterozygosity were 3.8387, 2.4027, 0.9787, 0.5565, and 0.5528, respectively. The
      31 microsatellite markers used were polymorphic and suitable for analyzing the
      genetic structure of cats. The population of orange tabby cats was confirmed to
      be a well-outbred stock. 

PMID- 25867324
TI  - Isolation and characterization of polymorphic microsatellite loci for
      Pachycrepoideus vindemmiae (Rondani) (Hymenoptera: Pteromalidae).
AB  - The parasitoid wasp Pachycrepoideus vindemmiae (Rondani) is a common pupal
      parasitoid of many fly pests that is distributed worldwide. This organism can be
      used for biological control in orchards or livestock farms. Identifying
      polymorphic microsatellite loci would be useful for analyzing the population
      genetic structure of the parasitoid. In the current study, based on a modified
      biotin-capture method, 10 polymorphic microsatellite loci were isolated and
      characterized for the insect, 7 of which did not deviate from Hardy-Weinberg
      equilibrium. The allelic number per locus varied from 3-7 (N = 30). The expected
      and observed heterozygosities of 10 loci ranged from 0.369-0.775 and from 0.300
      0.867, respectively. 

PMID- 25867325
TI  - EGFR gene polymorphisms -216G>T and -191C>A are risk markers for gastric cancer
      in Mexican population.
AB  - Epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein with
      tyrosine-kinase activity that plays an important role in multiple cellular
      functions. EGFR overexpression has been observed in several types of tumors and
      it is significantly associated with disease stage, survival, prognosis, and
      progression of cancer. The polymorphisms -216G>T, -191C>A, and (CA)n first
      intervening sequence (IVS1) have been related to EGFR overexpression and have
      been studied in several types of cancer, but not in gastric cancer (GC). The aim
      of this study was to determine the association of these 3 polymorphisms and GC.
      Genomic DNA from 68 GC patients and 102 healthy blood donors were analyzed.
      Polymorphisms were identified by DNA-sequencing (-216G>T and -191C>A) and
      GeneScan (CA)n IVS1. The results showed that the distribution of the -216G>T and 
      191C>A genotypes differed between groups (P < 0.05). The odds ratio for the 
      216TT genotype was 4.59 (95% confidence interval = 1.55-13.54, P < 0.05) and
      10.71 (95% confidence interval = 2.31-49.59, P < 0.05) for the -191AA genotype,
      both in a recessive model. The genotype and allele distributions of the (CA)n
      IVS1 repeat was similar in both groups. In conclusion, the -216TT and -191AA
      genotypes and GA haplotype of the EGFR gene were found to be associated with an
      increased risk of gastric cancer in a Mexican population.

PMID- 25867326
TI  - Associations between INSR and MTOR polymorphisms in type 2 diabetes mellitus and
      diabetic nephropathy in a Northeast Chinese Han population.
AB  - We explored the associations of INSR and mTOR, 2 key genes in the insulin
      signaling pathway, and the susceptibility to type 2 diabetes mellitus and
      diabetic nephropathy. Three single-nucleotide polymorphisms (SNPs) (rs1799817,
      rs1051690, and rs2059806) in INSR and 3 SNPs (rs7211818, rs7212142, and
      rs9674559) in mTOR were genotyped using the Sequenom MassARRAY iPLEX platform in
      89 type 2 diabetes patients without diabetic nephropathy, 134 type 2 diabetes
      patients with diabetic nephropathy, and 120 healthy control subjects. Statistical
      analysis based on unconditional logistic regression was carried out to determine
      the odds ratio (OR) and 95% confidence interval (95%CI) for each SNP. Combination
      analyses between rs2059806 and rs7212142 were also performed using the X(2) test
      and logistic regression. Among these 6 SNPs, 4 (rs1799817, rs1051690, rs7211818,
      and rs9674559) showed no association with type 2 diabetes mellitus or diabetic
      nephropathy. However, rs2059806 in INSR was associated with both type 2 diabetes
      mellitus (P = 0.033) and type 2 diabetic nephropathy (P = 0.018). The rs7212142
      polymorphism in mTOR was associated with type 2 diabetic nephropathy (P = 0.010,
      OR = 0.501, 95%CI = 0.288- 0.871), but showed no relationship with type 2
      diabetes mellitus. Combination analysis revealed that rs2059806 and rs7212142 had
      a combined effect on susceptibility to type 2 diabetes mellitus and diabetic
      nephropathy. Our results suggest that both INSR and mTOR play a role in the
      predisposition of the Han Chinese population to type 2 diabetic nephropathy, but
      the genetic predisposition may show some differences.

PMID- 25867327
TI  - Clinical significance of lymphatic vessel invasion in stage I non-small cell lung
      cancer patients.
AB  - The aim of this retrospective study was to evaluate the prognostic influence of
      lymphatic vessel invasion (LVI) in stage I non-small cell lung cancer (NSCLC)
      patients. From January 2004 to December 2007, LVI was detected in 57 patients
      with T1N0M0 NSCLC; therefore, 114 patients with the same pathology, T stage, and
      surgery method, but without LVI, were selected as the control group to compare
      survival. The overall survival and relapse-free survival rates were estimated
      using the Kaplan-Meier method, log-rank test, and Cox proportional hazards
      analysis. The average follow-up length was 59.94 +/- 23.1 months. The 5-year
      overall survival rates of the LVI-negative and the LVI-positive groups were 90.54
      and 70.1%, respectively (P = 0.002). A multivariate analysis revealed LVI to be
      an independent predictive factor (hazard ratio = 4.562; P = 0.004). The 5-year
      overall survival rates for patients who received postoperative adjunctive therapy
      and those who did not in the LVI-positive group were 88.2 and 61.5%,
      respectively, with a P value less than 0.05 in both univariate and multivariate
      analyses. LVI is a poor prognostic factor in stage I NSCLC patients;
      postoperative adjunctive therapy is needed to improve the prognosis of NSCLC
      patients with LVI.

PMID- 25867328
TI  - Identification of aac(2')-I type b aminoglycoside-modifying enzyme genes in
      resistant Acinetobacter baumannii.
AB  - The aim of this study was to investigate the mechanism underlying the drug
      resistance of Acinetobacter baumannii toward aminoglycosides. A total of 32 A.
      baumannii strains were identified by molecular identification and subsequently
      isolated. The isolates were then amplified by polymerase chain reaction to
      analyze the 9 aminoglycoside-modifying enzyme genes and 7 16S rRNA methylase
      genes. Five types of aminoglycoside-modifying enzyme genes and 1 type of 16S rRNA
      methylase gene were detected in the 32 drug-resistant A. baumannii strains.
      Positive genes included 7 detection modes, of which the all-6-gene-positive mode
      aac(2')-Ib+aac(3)-I+aac(6')-Ib+ant(3'')-I+aph(3')-I+armA exhibited the largest
      number of strains (12, 37.5%). The resistance of A. baumannii against
      aminoglycosides resulted from the presence of 5 types of aminoglycoside-modifying
      enzyme genes and the 16S rRNA methylase gene armA. This study is the first to
      isolate the aac(2')-Ib aminoglycoside-modifying enzyme gene from A. baumannii in
      a domestic clinical setting. 

PMID- 25867329
TI  - A new strategy for complete identification of sea buckthorn cultivars by using
      random amplified polymorphic DNA markers.
AB  - DNA fingerprinting is both a popular and important technique with several
      advantages in plant cultivar identification. However, this technique has not been
      used widely and efficiently in practical plant identification because the
      analysis and recording of data generated from fingerprinting and genotyping are
      tedious and difficult. We developed a novel approach known as a cultivar
      identification diagram (CID) strategy that uses DNA markers to separate plant
      individuals in a more efficient, practical, and referable manner. A CID was
      manually constructed and a polymorphic marker was generated from each polymerase
      chain reaction for sample separation. In this study, 67 important sea buckthorn
      cultivars cultivated in China were successfully separated with random amplified
      polymorphic DNA markers using the CID analysis strategy, with only seven 11
      nucleotide primers employed. The utilization of the CID of these 67 sea buckthorn
      cultivars was verified by identifying 2 randomly chosen groups of cultivars among
      the 67 cultivars. The main advantages of this identification strategy include
      fewer primers used and separation of all cultivars using the corresponding
      primers. This sea buckthorn CID was able to separate any sea buckthorn cultivars
      among the 67 studied, which is useful for sea buckthorn cultivar identification,
      cultivar-right-protection, and for the sea buckthorn nursery industry in China. 

PMID- 25867330
TI  - Phosphorylation of the GluN1 subunit in dorsal horn neurons by remifentanil: a
      mechanism for opioid-induced hyperalgesia.
AB  - Remifentanil (an ultra-short acting MU-opioid receptor agonist) use has been
      associated with acute opioid tolerance and hyperalgesia. Previous
      electrophysiological studies have shown that remifentanil elicits rapid and
      prolonged upregulation of N-methyl-D-aspartate receptor (NMDAR) currents.
      However, the effect of remifentanil on the levels of the GluN1 subunit of the
      NMDAR in dorsal horn neurons (DHNs) has not been reported. We investigated the
      effect of remifentanil, along with ketamine (NMDAR antagonist) and naloxone (MU
      opioid receptor antagonist), on GluN1 mRNA levels and the amount of
      phosphorylated GluN1 in primary cultures of embryonic rat DHNs. DHNs were
      isolated from 18-19-day rat embryos and treated with remifentanil or vehicle for
      1 h. GluN1 mRNA and protein levels, determined by real time reverse transcription
      polymerase chain reaction (RT-PCR) and Western blot, respectively, were
      significantly and persistently increased by remifentanil exposure compared with
      the control group (P < 0.05). These results may partially account for the
      mechanism of remifentanil-induced hyperalgesia. This increase was prevented by
      ketamine (NMDAR antagonist) and naloxone (MU-opioid receptors antagonist), thus
      providing a potential therapeutic mechanism for the prevention of opioid-induced
      hyperalgesia. 

PMID- 25867332
TI  - Screening of rice (Oryza sativa L.) OsPR1b-interacting factors and their roles in
      resisting bacterial blight.
AB  - PR genes, a type of genetic marker, are constitutively expressed at background
      levels, while being easily inducible by pathogenic bacteria. By using a yeast two
      hybrid technique, four rice (Oryza sativa L.) OsPR1b-interacting factors were
      screened. Homozygous plants overexpressing OsPR1b were prepared by transgenic
      technology. We postulated that OsPR1b may participate in the resistance signaling
      pathway of rice. Of simultaneous treatments with hormones and pathogenic
      bacteria, exogenously applying JA and ET significantly increased the expression
      level of OsPR1b genes in seedlings. Compared with the control group that was
      inoculated with water, inoculation with a mixture of water and pathogenic
      bacteria hardly affected the expression level of OsPR1b gene, while cotreatment
      with SA and pathogenic bacteria slightly upregulated the expression level.
      However, cotreatment with JA or ET and pathogenic bacteria managed to
      significantly upregulate the expression level of the OsPR1b gene by 4.8 or 5.7
      fold. PR genes, which are sensitive, are prone to many unknown factors during
      expression, and the detailed regulatory mechanisms in rice still require in-depth
      studies.

PMID- 25867331
TI  - Gene expression profiles of primary retinal pigment epithelial cells from
      apolipoprotein E knockout and human apolipoprotein E2 transgenic mice.
AB  - Age-related macular degeneration (AMD) causes visual impairment in the elderly.
      In non-neovascular AMD, studies involving human subjects have suggested potential
      involvement of aberrant lipid metabolism. However, there have been no reports on
      gene expression patterns in animal models of non-neovascular AMD with abnormal
      lipid metabolism such as apolipoprotein E knockout and human apolipoprotein E2
      transgenic mice. Transcriptome analysis was performed using retinal pigment
      epithelium cells of apoE knockout and apolipoprotein E2 mice using microarray
      analysis. C57BL/6, Rxrb, Pparbp, Vldlr, and Edf1, which are primarily related to
      lipid metabolism, were upregulated, while Tgfbr1 and Pdgfb, which are related to
      pathologic angiogenesis in AMD, were downregulated in both types of mice.
      Apolipoprotein E knockout and apolipoprotein E2 mice showed characteristic gene
      expression patterns in the transcriptome analysis of primary retinal pigment
      epithelium cells. These results suggest that specific genes associated with lipid
      metabolism and angiogenesis are involved in the pathogenesis and progression of
      AMD. 

PMID- 25867333
TI  - Sequence characterization and phylogenetic analysis of Toll-like receptor (TLR) 4
      gene in the Tibetan macaque (Macaca thibetana).
AB  - In this study, the complete coding region sequence of an innate immune-related
      TLR4 gene was obtained from the Tibetan macaque (Macaca thibetana) genome via PCR
      and direct sequencing. The sequence had a total length of 2481 bp, contained 3
      complete exons, and encoded 826 amino acids (AAs); its isoelectric point was
      5.703, and the molecular weight was 94.72 kDa. The high structure prediction
      showed that the protein was comprised of one extracellular region, one
      transmembrane region, and one intracellular region. There were 48 potential
      functional sites in the protein, including glycosylation, phosphorylation, and
      acetylation sites. A homology analysis among 9 primate species, including the
      Tibetan macaque, human, chimpanzee, gibbon, rhesus macaque, cynomolgus monkey,
      pig-tailed monkey, squirrel monkey, and small-eared galago, showed that the
      homology of the nucleotide and AA sequences ranged from 60.9-99.5% and 51.4-
      99.0%, respectively. Higher variability was identified in the extracellular
      region of the TLR4 protein, and its variable sites accounted for 88.79% (AA) of
      the total variable sites. Additionally, the number of AAs at the 3' end of the
      intracellular region was notably different among the primate lineages. The
      phylogenetic tree based on TLR4 gene exons of 9 primate species showed that the
      Tibetan macaque clustered with the rhesus macaque, cynomolgus monkey, and pig
      tailed monkey; it was most distant from the small-eared galago. This study will
      provide an important basis for further study on the expression, regulation, and
      polymorphism of the TLR4 gene and the relationship between polymorphisms and host
      disease susceptibility. 

PMID- 25867334
TI  - Phylogenetic analysis of Gansu sheeppox virus isolates based on P32, GPCR, and
      RPO30 genes.
AB  - Two outbreaks of sheeppox in sheep have occurred in Gansu Province, China. The
      P32, GPCR, and RPO30 genes were used as markers for differential diagnosis. We
      confirmed that the outbreaks were caused by sheeppox virus. Sequence and
      phylogenetic analysis of the P32, GPCR, and RPO30 genes revealed a close
      relationship between the 2 isolates and Chinese sheeppox viruses. Because ill
      sheep were imported from Jingyuan, another county of Gansu Province, our results
      strongly suggest the importance of veterinary surveillance prior to
      transportation.

PMID- 25867335
TI  - Single nucleotide polymorphism in the RECQL5 gene increased osteosarcoma
      susceptibility in a Chinese Han population.
AB  - In this study, we investigated the association between a RECQL genetic
      polymorphism and osteosarcoma in a Chinese population. We selected rs820196 in
      the RECQL5 gene and genotyped 185 patients with osteosarcoma and 201 age- and
      gender-matched non-cancer controls. We found that the CC genotype was more
      frequent in the osteosarcoma group compared to the control group (P = 0.011). We
      also found that the C allele was more common in osteosarcoma patients than that
      in control subjects (P = 0.004). Our results suggested that the RECQL5 genetic
      polymorphism was associated with osteosarcoma in a Chinese population.

PMID- 25867336
TI  - DNA barcoding for efficient identification of Ixiolirion species (Ixioliriaceae).
AB  - Ixiolirion is a genus of unresolved taxonomy. DNA barcoding is a technique that
      allows species identification using standardized DNA sequences. In this study, a
      total of 23 individuals, representing 2 Chinese Ixiolirion species, were sampled
      to test the effectiveness of 3 DNA barcodes [internal transcribed spacer (ITS),
      chloroplast tRNA intron, and megakaryocyte-associated tyrosine kinase] for
      species identification. Of the 3 DNA barcodes, ITS displayed the maximum level of
      polymerase chain reaction and sequencing success as well as the highest sequence
      variation. Intra-specific sequence distances of ITS, chloroplast tRNA intron, and
      megakaryocyte-associated tyrosine kinase were 0, 0, and 0-0.1%, respectively,
      with 8.3, 0.6, and 0.5% as mean inter-specific distances, respectively. All
      individuals of each species formed a monophyletic group (clade) in the neighbor
      joining trees constructed using the 3 single-DNA barcodes. Our results
      demonstrated that ITS, chloroplast tRNA intron, and megakaryocyte-associated
      tyrosine kinase DNA markers could be used to identify Ixiolirion species. Our
      results indicate that DNA barcoding provides a reliable and effective means for
      discriminating Ixiolirion species, and is a robust tool for resolving taxonomic
      controversies of Ixiolirion in combination with morphology-based taxonomy.

PMID- 25867337
TI  - Selectional versus mutational mechanism underlying genomic features of bacterial
      strand asymmetry: a case study in Clostridium acetobutylicum.
AB  - Strand biases are widespread in bacterial genomes. In this review, we discuss 5
      types of bias, including gene orientation, the number of open reading frames,
      nucleotide composition, substitution rate, and gene length, between leading and
      lagging strands during replication. For each type of strand bias, related studies
      were summarized and Clostridium acetobutylicum ATCC 824 was used as a
      representative example to illustrate bias. Our results in C. acetobutylicum
      indicate that there is little asymmetry between 2 replication strands on open
      reading frame number and gene length, whereas the other 3 features presented
      significant strand bias. The underlying mechanisms of mutation and/or selection
      are discussed. It is hoped that this review will improve the understanding of the
      extent and reasons for various types of strand bias in bacterial genomes. 

PMID- 25867338
TI  - Genetic variations in microRNA genes and susceptibility to hepatocellular
      carcinoma.
AB  - We conducted a hospital-based case-control study to investigate the effect of the
      miR-146aG>C and miR-499A>G polymorphisms on the risk of hepatocellular carcinoma
      (HCC) in a Chinese population. This study was 1:1 matched case-control study
      consisting of 184 HCC patients and 184 control subjects. miR-146aG>C and miR
      499A>G polymorphisms were genotyped by polymerase chain reaction-restriction
      fragment length polymorphism. Multivariate regression analyses showed that
      subjects carrying the miR-146a G allele and miR-499 G allele were associated with
      a non-significant increased risk of HCC compared with subjects with the
      homozygous allele, with adjusted odds ratios (95% confidence interval) of 1.38
      (0.97-1.84) and 1.40 (0.99-2.08), respectively. Moreover, subjects carrying the
      miR-499 A allele showed a greatly increased risk of HCC in subjects infected with
      HBV compared with subjects carrying the miR-499 A allele, with an adjusted odds
      ratio (95% confidence interval) of 1.53 (1.34-2.41). In conclusion, the miR
      146aG>C and miR-499A>G polymorphisms do not have a role in the genetic
      susceptibility to HCC.

PMID- 25867339
TI  - Pedigrees of infertile Chinese men with Y chromosome microdeletions derived from
      natural transmission and de novo mutation.
AB  - Y chromosome microdeletions can cause male infertility and are classified as
      natural transmission and de novo mutations. To examine the source of these
      deletions in Chinese men and to provide a theoretical and laboratory basis for
      genetic counseling, patients from Northeast China with primary male infertility
      (N = 22) and their fathers were investigated. Karyotype analysis was performed on
      peripheral blood lymphocytes using standard G-banding. Multiplex polymerase chain
      reaction amplification using 18 specific sequence-tagged sites was selected to
      detect Y chromosome microdeletions. De novo mutations were observed in 17 father
      son pairs, leading to a mutation rate of 77.27% (17/22), while the vertical
      transmission of Yq AZFc microdeletions was detected in 5 cases of the families
      investigated (29.41%, 5/17). There were no statistically significant differences
      between vertically transmitted and de novo mutations in men with AZFc deletions
      regarding age, testicular volume, and reproductive hormone levels. Most Y
      chromosome microdeletions in men from Northeast China are the result of de novo
      mutations via natural conception, and men with Yq AZFc deletions showed no clear
      differences between vertical transmission and de novo mutations.

PMID- 25867340
TI  - Assessment of genetic diversity and relationships among wild and cultivated
      Tunisian plums (Prunus spp) using random amplified microsatellite polymorphism
      markers.
AB  - The usefulness of random amplified microsatellite polymorphism markers to study
      the genetic diversity and relationships among cultivars belonging to Prunus
      salicina and P. domestica and their wild relatives (P. insititia and P. spinosa)
      was investigated. A total of 226 of 234 bands were polymorphic (96.58%). The 226
      random amplified microsatellite polymorphism markers were screened using 15
      random amplified polymorphic DNA and inter-simple sequence repeat primers
      combinations for 54 Tunisian plum accessions. The percentage of polymorphic bands
      (96.58%), the resolving power of primers values (135.70), and the polymorphic
      information content demonstrated the efficiency of the primers used in this
      study. The genetic distances between accessions ranged from 0.18 to 0.79 with a
      mean of 0.24, suggesting a high level of genetic diversity at the intra- and
      interspecific levels. The unweighted pair group with arithmetic mean dendrogram
      and principal component analysis discriminated cultivars efficiently and
      illustrated relationships and divergence between spontaneous, locally cultivated,
      and introduced plum types. These procedures showed continuous variation that
      occurs independently of the status of the species and geographical origin of the
      plums. In this study, random amplified microsatellite polymorphism was found to
      be as a reliable molecular marker for fingerprinting and for examining the
      diversity study of the plum and its relatives.

PMID- 25867341
TI  - Positive selection sites in tertiary structure of Leguminosae chalcone isomerase
      1.
AB  - Isoflavonoids and the related synthesis enzyme, chalcone isomerase 1 (CHI1), are
      unique in the Leguminosae, with diverse biological functions. Among the
      Leguminosae, the soybean is an important oil, protein crop, and model plant. In
      this study, we aimed to detect the generation pattern of Leguminosae CHI1. Genome
      wide sequence analysis of CHI in 3 Leguminosae and 3 other closely related model
      plants was performed; the expression levels of soybean chalcone isomerases were
      also analyzed. By comparing positively selected sites and their protein
      structures, we retrieved the evolution patterns for Leguminosae CHI1. A total of
      28 CHI and 7 FAP3 (CHI4) genes were identified and separated into 4 clades: CHI1,
      CHI2, CHI3, and FAP3. Soybean genes belonging to the same chalcone isomerase
      subfamily had similar expression patterns. CHI1, the unique chalcone isomerase
      subfamily in Leguminosae, showed signs of significant positive selection as well
      as special expression characteristics, indicating an accelerated evolution
      throughout its divergence. Eight sites were identified as undergoing positive
      selection with high confidence. When mapped onto the tertiary structure of CHI1,
      these 8 sites were observed surrounding the enzyme substrate only; some of them
      connected to the catalytic core of CHI. Thus, we inferred that the generation of
      Leguminosae CHI1 is dependent on the positively selected amino acids surrounding
      its catalytic substrate. In other words, the evolution of CHI1 was driven by
      specific selection or processing conditions within the substrate.

PMID- 25867342
TI  - Effect of TIEG1 on apoptosis and expression of Bcl-2/Bax and Pten in leukemic
      cell lines.
AB  - We examined the effect of transforming growth factor-b inducible early gene-1
      (TIEG1) on the apoptosis of leukemic cell lines and expression of B-cell lymphoma
      2 (Bcl-2) and phosphatase and tensin homolog (Pten). Four leukemic cell lines (HL
      60, U937, Raji, and K562) were treated with 0, 1, 5, 10, and 20 ng/mL TIEG1,
      respectively. The cell growth inhibitory ratio was assessed using the MTT assay.
      An inhibitory curve was drawn, and half-maximal inhibitory concentration was
      calculated. Additionally, 1640 culture medium containing 10 ng/mL TIEG1 was used
      to culture leukemic cell lines for 0, 6, 12, 24, and 48 h. The apoptosis of each
      cell line at different time points was detected by flow cytometry. Total RNA was
      extracted before reverse transcription-polymerase chain reaction. The products of
      this reaction were analyzed by electrophoresis, and the expression of Bcl-2/Bcl-2
      associated X protein (Bax) and Pten were detected. After treatment with TIEG1,
      proliferation of the 4 leukemic cell lines was inhibited both time- and dose
      dependently. During apoptosis induction, the expression of Bcl-2 was decreased
      and the expressions of Bax and Pten were increased in the 4 leukemic cell lines
      induced by TIEG1 (P < 0.05). TIEG1 can inhibit the proliferation of leukemic
      cells and induce their apoptosis in a time- and dose-dependent manner. A close
      relationship exists between Bcl-2/Bax and Pten expression and cell apoptosis
      induced by TIEG1.

PMID- 25867343
TI  - Characterization of agronomic and quality traits and HSW-G5 compositions from the
      progenies of common wheat (Triticum aestivum L.) with different protein content.
AB  - High molecular weight glutenin subunits (HMW-GS) play an essential role in wheat
      processing quality. In this study, we evaluated the genetic pattern with HMW-GS
      composition between generations and examined whether agronomic and quality traits
      were correlated with each other. A wheat (Triticum aestivum L.) cultivar with
      high protein content and 2 cultivars with low protein content were subjected to a
      reciprocal cross. Sixteen agronomic and 4 quality characteristics were
      investigated. A total of 216 seeds from each F2 generation were chosen randomly
      and analyzed for HMW-GS composition using sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis. Agronomic and quality characteristics were not significantly
      different between reciprocal crosses, indicating no cytoplasmic effect on the
      characteristics studied. The separation ratio of 2 HMW-GS loci was 9:3:3:1,
      indicating no linkage between any 2 loci. The novel HMW-GS N was detected in
      cultivar R145, which did not follow the Mendelian segregation ratio. A Glu-A1a(1)
      band was not detected in 1 individual from Tian8901xR145. Average grain weight
      per spike was significantly correlated with quality characteristics and may be a
      suitable criterion for selecting high protein content in wheat breeding programs.

PMID- 25867344
TI  - Fengshui forests conserve genetic diversity: a case study of Phoebe bournei
      (Hemsl.) Yang in southern China.
AB  - Fengshui forests (sacred groves) are important in traditional Chinese culture and
      home to many endangered species. These forests may provide protection for some
      endangered plant species outside the nature reserves, but little is known about
      their role in genetic conservation. Using inter-simple sequence repeat (ISSR)
      markers, we compared the genetic diversity of 6 populations of Phoebe bournei
      (Hemsl.) Yang, a commercially important woody species, which is under second
      class national protection and endemic to China. Samples were collected from the
      nature reserves and Fengshui forests in southern China. Herein, we show that
      Fengshui forest populations are capable of maintaining some level of genetic
      diversity. For nature reserve populations, the average NA and NE were 1.58 and
      1.39, respectively; and for Fengshui forests, they were 1.39 and 1.12,
      respectively. For nature reserve populations, Nei's gene diversity (H) and
      Shannon's index (I) were 0.32 and 0.11, respectively; and for Fengshui forests,
      they were 0.22 and 0.07, respectively. We discuss the reasons for the genetic
      differences between populations of the Fengshui forests and nature reserves and
      propose conservation strategies for the Fengshui forest.

PMID- 25867345
TI  - Association of heat shock protein 70 expression with rat myocardial cell damage
      during heat stress in vitro and in vivo.
AB  - To investigate the mechanism of sudden death as a result of stress-induced damage
      to heart tissue and myocardial cells and to investigate the cardioprotective role
      of Hsp70 during heat stress, the distribution and expression of Hsp70 was
      evaluated in the heart cells of heat-stressed rats in vivo and heat-stressed H9c2
      cells in vitro. After exposure to heat stress at 42 degrees C for different
      durations, we observed a significant induction of CK, CK-MB, and LDH as well as
      pathologic lesions characterized by acute degeneration, suggesting that cell
      damage occurs from the onset of heat stress. Immunocytochemistry showed that
      Hsp70 was distributed mainly in the cytoplasm of myocardial cells in vivo and in
      vitro. Hsp70-positive signals in the cytoplasm were more prominent in intact
      areas than in degenerated areas after 60 min of heat stress. Hsp70 protein levels
      in myocardial cells in vitro decreased from the beginning to the end of heat
      stress. Hsp70 protein levels in rat heart tissues in vivo decreased gradually
      with prolonged heat stress, with a slight increase at the beginning of heat
      stress. These results indicate that Hsp70 plays a role in the response of cardiac
      cells to heat stress and that decreased Hsp70 levels are associated with damage
      to rat myocardial cells in vitro and in vivo. Significant differences were found
      in hsp70 mRNA, which began to increase after 20 min of heat stress in vitro and
      after 40 min in vivo. This indicates that hysteresis is involved in mRNA
      expression after heat stress in vivo. 

PMID- 25867346
TI  - Copy number and integration sites in growth hormone transgenic goats.
AB  - Transgenic goats have been utilized for years to produce valuable protein.
      However, when transgenic goats are produced by random integration of inserted
      genes into cells, the copy number and integration sites of these genes in the
      goat genome are typically indefinite. Most polymerase chain reaction (PCR)-based
      methods that have been utilized to determine copy number and integration sites of
      inserted genes in the genome require complicated manipulations. In this study, we
      used quantitative real-time PCR and thermal asymmetric interlaced-PCR to
      determine copy number and integration sites of the inserted genes, respectively.
      Copies of transgenic goat lines GHcd-2 and GHcd-7 were 12.95 +/- 0.18 and 12.24
      +/- 1.12, respectively. Two integration sites, located in chromosomes 3 and 11
      and referred to as tg1 and tg2, were identified by thermal asymmetric interlaced
      PCR. Junction PCR was then performed to confirm the integration sites of growth
      hormone transgenic goats. Transgenic copy number and integration sites were
      determined, which will be useful for determining the relationship between the
      growth hormone expression, copy number, and integration sites. 

PMID- 25867347
TI  - Identification of an SCAR marker related to female phenotype in Idesia polycarpa
      Maxim.
AB  - Idesia polycarpa Maxim. is a dioecious species. Because of the lack of
      morphological and cytological methods available for identifying its sex during
      the long juvenile stage, the application of molecular markers in sex
      identification may facilitate sex determination in the seedling stage. The
      objective of this study was to use sequence-related amplified polymorphism to
      identify sex-linked markers in I. polycarpa and convert these markers into
      sequence-characterized amplified region markers, which are much easier to
      identify. A total of 342 primer combinations were screened and 2770 bands were
      examined. Only me14/em8 could amplify a specific fragment (210 base pairs) in all
      female but none in male plants. We analyzed this fragment using GenBank and found
      that the sequence similarity was 80% to the Populus trichocarpa clone POP006-H09
      (sequence ID: gb|AC212923.1|) and that of the deduced amino acid sequence was 73%
      to the integrase of Mendicago truncatula (sequence ID: gb|ABD28291.1|) and 71% to
      the predicted retrotransposon integrase-like protein 1-like in Cicer arietinum
      (sequence ID: ref|XP 004515460.1|) (NCBI database through December 17, 2013).
      This fragment was converted into a stable and simple sequence-characterized
      amplified region marker approximately 200 base pairs in length. This marker can
      be utilized for early sexual identification in I. polycarpa, which will
      facilitate future breeding programs.

PMID- 25867348
TI  - 14-3-3 gene expression in regenerating rat liver after 2/3 partial hepatectomy.
AB  - 14-3-3 Proteins are a ubiquitous family of molecules that participate in protein
      kinase signaling pathways in all eukaryotic cells. Functioning as
      phosphoserine/phosphothreonine-binding modules, 14-3-3 proteins participate in
      the phosphorylation-dependent protein-protein interactions that control
      progression through the cell cycle, initiation and maintenance of DNA damage
      checkpoints, activation of MAP kinases, prevention of apoptosis, and coordination
      of integrin signaling and cytoskeletal dynamics. During liver regeneration after
      partial hepatectomy, normally quiescent hepatocytes undergo hypertrophy and
      proliferation to restore the liver mass. In this study, we investigated the
      expression patterns of 14-3-3 mRNAs in regenerating rat liver after 2/3 partial
      hepatectomy using real-time quantitative reverse transcription-polymerase chain
      reaction. All mRNAs of the 14-3-3 7 isotypes were expressed at 10 time points.
      Upregulation of 14-3-3x mRNA expression and downregulation of 14-3-3s mRNA
      expression from 0 to 6 h may play important roles in the entry into S-phase.
      Downregulation of 14-3-3b, g, s, h, and t mRNA expression from 24 to 30 h, when
      compared to 0 h, was closely related to entry into mitosis. 

PMID- 25867349
TI  - High-resolution melting curve analysis of the ADSL and LPL genes and their
      correlation with meat quality and blood parameters in chickens.
AB  - Adenylosuccinate lyase (ADSL) and lipoprotein lipase (LPL) are key enzymes in the
      metabolism of inosine monophosphate (IMP) and fat mass, which are important
      factors in meat quality evaluation. In this study, we selected 50 hens from the
      ISA B-line layers and Guangxi Yellow chickens, slaughtered the chickens at 120
      days old, and analyzed polymorphisms in the ADSL and LPL genes using the high
      resolution melting curve method. Blood lipid parameters, intramuscular fat (IMF),
      and IMP content were higher (P < 0.05) in Guangxi Yellow chickens than in ISA B
      line layers, while LPL activity was lower (P < 0.05). In exon 2 of the ADSL gene,
      a C3484T mutation was identified. In both breeds, the CC genotype showed the
      highest IMP, and IMP was the lowest in the TT genotype. In the 5? regulatory
      region of the LPL gene, a C293T mutation was identified. In both breeds, the CC
      genotype showed the lowest LPL and IMF, while IMF was the highest in the TT
      genotype. The percentages of individuals with the TT type in the ADSL gene, which
      was associated with the lowest IMP, were 16.0 and 52.0% in Guangxi chickens and
      ISA layers, respectively. The percentages of individuals with the CC type of the
      LPL gene, which was associated with the lowest LPL and IMF, were 28.0 and 44.0%,
      respectively. The ADSL and LPL gene mutations are correlated with differences in
      meat quality in different chicken breeds, and high-resolution melting curve is an
      effective prediction technology for these mutations.

PMID- 25867350
TI  - Gene expression profile analysis of testis and ovary of oriental river prawn,
      Macrobrachium nipponense, reveals candidate reproduction-related genes.
AB  - This study utilized high-throughput RNA sequencing technology to identify
      reproduction- and development-related genes of Macrobrachium nipponense by
      analyzing gene expression profiles of testis and ovary. More than 20 million 1 x
      51-bp reads were obtained by Illumina sequencing, generating more than 7.7 and
      11.7 million clean reads in the testis and ovary library, respectively. As a
      result, 10,018 unitags were supposed to be differentially expressed genes (DEGs)
      between ovary and testis. Compared to the ovary library, 4563 (45.5%) of these
      DEGs exhibited at least 6-fold upregulated expression, while 5455 (54.5%) DEGs
      exhibited at least 2-fold downregulated expression in the testis. The Gene
      Ontology (GO) enrichment analysis showed that 113 GO terms had potential
      molecular functions in reproduction. The Kyoto Encyclopedia of Genes and Genomes
      results revealed that the most important pathways may be relevant to reproduction
      and included 7 pathways. Forty-two genes were identified as reproduction-,
      development-, and sex-related genes based on GO classification and sequence
      comparison with other publications, including male reproductive-related LIM
      protein, spermatogenesis-associated protein, gametocyte-specific factor 1, VASA
      like protein, vitellogenin, sex-determining protein fem-1, and other potential
      candidates. These results will advance research in the field of molecular
      genetics in M. nipponense and offer a valuable resource for further research
      related to reproduction in crustaceans. 

PMID- 25867351
TI  - Sequence variation and gene duplication at the MHC DRB loci of the spotted seal
      Phoca largha.
AB  - The major histocompatibility complex (MHC) is one of the most important genetic
      systems associated with resistance to infectious diseases in vertebrates. The
      spotted seal (Phoca largha) is one of the most endangered species in China. In
      this study, we present the first step in the molecular characterization of a DRB
      like locus in the spotted seal by analyzing the nucleotide sequence of the
      polymorphic exon 2 segments, a 288-nucleotide sequence. By examining the segment
      from a group of 41 individuals, 28 alleles were identified. No deletion,
      insertion, or exceptional stop codon was detected, suggesting that these alleles
      could be functional in vivo. The nucleotide and amino acid sequences of the
      segment both showed a relatively high level of similarity (nucleotides 97%; amino
      acids 98%) to those of Meles meles and Zalophus californianus. The high level of
      spotted seal MHC-DRB polymorphism revealed in the present study has not been
      reported for the Phocidae and could be a consequence of the small spotted seal
      population adapting to the Bohai Sea, which probably has a relatively high level
      of pathogens. 

PMID- 25867352
TI  - Traditional risk factors and angiotensin-converting enzyme insertion/deletion
      gene polymorphism in coronary artery disease.
AB  - We investigated whether the insertion/deletion (I/D) polymorphism in the
      angiotensin-converting enzyme (ACE) gene and serum ACE levels are associated with
      traditional risk factors of coronary artery disease (CAD). We enrolled 250
      individuals without CAD and 750 individuals suffering from CAD who were
      angiographically diagnosed. Biochemical risk factors, the ACE (I/D) gene
      polymorphism, and ACE serum levels were compared. ACE genotypes were determined
      using real-time polymerase chain reaction. ACE serum levels were determined using
      an enzyme-linked immunosorbent assay. Lipid parameters were determined
      spectrophotometrically using an autoanalyzer. Compared to the control group, the
      CAD group showed significantly higher serum ACE levels (P < 0.001). The highest
      ACE levels were found in those with the DD genotype. Other genotypes also
      presented statistically significant differences. We observed a significant
      difference between the control and coronary patient groups regarding the levels
      of total cholesterol, triglyceride, high-density lipoprotein-cholesterol, and low
      density lipoprotein-cholesterol (P < 0.05). ACE (I/D) genotypes and serum ACE
      levels may be associated with risk factors and the development of CAD. 

PMID- 25867353
TI  - Protein-protein interaction network and mechanism analysis of hepatitis C.
AB  - We predicted potential genes and identified pathways associated with hepatitis C.
      The gene expression profiles of GSE40184 from blood samples and GSE38597 from
      liver biopsy samples were downloaded from the GEO database. Differentially
      expressed genes (DEGs) were recognized using the Limma Package. The Pearson
      correlation test was used to construct the co-expression network of DEGs. Gene
      set enrichment analysis was used to define significant functions and pathways for
      DEGs. A total of 165 DEGs in blood samples and 523 DEGs in liver biopsy samples
      were identified. Eight DEGs were common between these samples. Gene Ontology
      enrichment analysis showed that 165 DEGs in blood samples were significantly
      enriched regarding the response to protein binding, receptor binding, G-protein
      coupled receptor binding, cytokine receptor binding, and cytokine activity. The
      most significant term of the Kyoto Encyclopedia of Genes and Genomes pathway was
      the cytokine-cytokine receptor interaction. Protein-protein interaction network
      analysis indicated that three subnetworks with more nodes and edges were involved
      in these interactions. We used robust biomarkers that were differentially
      expressed in hepatitis C and determined their relevance in the biological
      function, signal pathways, protein-protein interaction network, and co-expression
      network of hepatitis C.

PMID- 25867354
TI  - Development and validation of single nucleotide polymorphism markers in
      Odontobutis potamophila from transcriptomic sequencing.
AB  - Transcriptome sequencing technology has been applied in the development and
      discovery of single nucleotide polymorphism (SNP) markers in fish. In this study,
      a panel of 120 expressed sequence tag (EST)-derived SNPs was selected by several
      selection filters from the resultant EST library of Odontobutis potamophila using
      Illumina Sequencing. In total, 37 SNPs from 120 putative SNPs were considered as
      the true SNPs using Sanger sequencing. For each SNP locus of 30 individuals of
      one wild population of O. potamophila that was successfully calculated, the
      number of alleles per locus was 2 with an observed heterozygosity of 0.0000
      0.9000 and an expected heterozygosity of 0.1000-0.5263. A total of 33 loci
      conformed to Hardy-Weinberg equilibrium (HWE), and 4 loci deviated from HWE after
      Bonferroni correction. These 33 SNP markers will benefit the studies of
      population genetic structure, population evolution analysis, and construction of
      a high-density linkage map of O. potamophila. 

PMID- 25867355
TI  - A Cu/Zn superoxide dismutase from Jatropha curcas enhances salt tolerance of
      Arabidopsis thaliana.
AB  - Superoxide dismutases (SODs) are involved in protecting plants against diverse
      biotic and abiotic stresses. In the present study, a novel Cu/Zn-SOD gene
      (JcCu/Zn-SOD) was cloned from Jatropha curcas L. Quantitative reverse
      transcription-polymerase chain reaction analysis revealed that JcCu/Zn-SOD is
      constitutively expressed in different tissues of J. curcas and induced under NaCl
      treatment. To characterize the function of this gene with respect to salt
      tolerance, the construct p35S:JcCu/Zn-SOD was developed and transformed into
      Arabidopsis using Agrobacterium-mediated transformation. Compared with wild-type,
      transgenic plants over-expressing JcCu/Zn-SOD showed enhanced tolerance to salt
      stress during germination, seedling establishment, and growth in terms of longer
      root, larger rosette area, and a larger number of leaves in addition to higher
      SOD activity levels under NaCl stress. In addition, over-expression of JcCu/Zn
      SOD resulted in lower monodialdehyde content in transgenic Arabidopsis compared
      to wild-type plants under the same NaCl stress. Therefore, JcCu/Zn-SOD can
      increase a plant salt stress tolerance potentially by reducing oxidant injury.

PMID- 25867356
TI  - Effects of Herceptin on circulating tumor cells in HER2 positive early breast
      cancer.
AB  - The objective of this study was to determine the changes in peripheral blood
      circulating tumor cells in HER2-positive early breast cancer before and after
      Herceptin therapy, and to explore the effects of the HER2 gene and Herceptin on
      circulating tumor cells. CK19 mRNA expression in peripheral blood was evaluated
      by qRT-PCR as an index of circulating tumor cells in 15 cases of HER-2-positive
      breast cancer and 18 cases of HER2-negative breast cancer before, and after
      chemotherapy as well. Ten cases of HER2-positive breast cancer continued on
      Herceptin therapy for 3 months after chemotherapy, and their peripheral blood was
      again drawn and assayed for CK-19 mRNA expression. Preoperatively, all cases of
      HER2-positive cancer were positive for CK19 mRNA in peripheral blood, but 6 cases
      of HER2-negative breast cancer were positive (33.3%), where there was a
      substantial difference between the two groups. After 6 cycles of adjuvant
      chemotherapy, CK19 positive rates in cases of HER2-positive and -negative breast
      cancer reduced by 93.3 and 11.1%, respectively, with a significant difference
      still existing. After 3 months of Herceptin therapy, expression of CK19 mRNA
      declined considerably in 10 cases of HER2 positive breast cancer (113.66 +/-
      88.65 vs 63.35 +/- 49.27, P = 0.025). HER-2 gene expression closely correlated
      with circulating tumor cells in peripheral blood of early breast cancer patients.
      Moreover, Herceptin, a monoclonal antibody for HER2, can reduce the number of
      circulating tumor cells, which can be an early predictive factor for Herceptin
      therapy effectiveness against breast cancer.

PMID- 25867357
TI  - Regulation of expression of sodA and msrA genes of Corynebacterium glutamicum in
      response to oxidative and radiative stress.
AB  - Promoters of genes encoding superoxide dismutase (sodA) and peptide methionine
      sulfoxide reductase (msrA) from Cory-nebacterium glutamicum were cloned and
      sequenced. Promoter region analysis of sodA-msrA was unable to identify putative
      sites of fixed eventual regulators except for possible sites of fixed OxyR and
      integra-tion host factor. A study of the regulation of these genes was performed
      using the lacZ gene of Escherichia coli as a reporter placed under the control of
      sequences downstream of sodA and msrA. In silico analysis was used to identify
      regulators in the genome of C. glutamicum, which revealed the absence of homologs
      of soxRS and arcA and the presence of inactive oxyR and putative candidates of
      the homologs of ahpC, ohrR, integration host factor, furA, IdeR, diphtheria toxin
      repressor, and mntR.

PMID- 25867358
TI  - Staging of type 2 diabetes mellitus.
AB  - There is currently no reported staging system for type 2 diabetes mellitus. Here,
      I attempted to stage type 2 diabetes mellitus in order to help clinicians,
      patients, and other interested individuals to effectively evaluate patient
      conditions. 

PMID- 25867359
TI  - Genetic dissection of agronomic traits in Capsicum baccatum var. pendulum.
AB  - Genetic mapping is very useful for dissecting complex agronomic traits. Genetic
      mapping allows for identification of quantitative trait loci (QTL), provide
      knowledge on a gene position and its adjacent region, and enable prediction of
      evolutionary mechanisms, in addition to contributing to synteny studies. The aim
      of this study was to predict genetic values associated with different agronomic
      traits evaluated in an F2 population of Capsicum baccatum var. pendulum.
      Previously, a reference genetic map for C. baccatum was constructed, which
      included 183 markers (42 microsatellite, 85 inter-simple sequence repeat, and 56
      random amplification of polymorphic DNA) arranged in 16 linkage groups. The map
      was used to identify QTL associated with 11 agronomic traits, including plant
      height, crown diameter, number of days to flowering, days to fruiting, number of
      fruits per plant, average fruit weight, fruit length, fruit diameter, fruit pulp
      thickness, soluble solids, and fruit dry weight. QTL mapping was performed by
      standard interval mapping. The number of small QTL effects ranged from 3-11, with
      a total of 61 QTL detected in 9 linkage groups. This is the first report
      involving QTL analysis for C. baccatum species.

PMID- 25867360
TI  - Effect of Tanshinone IIA intrathecal injections on pain and spinal inflammation
      in mice with bone tumors.
AB  - The study aimed to investigate the effect of intrathecal injections of Tanshinone
      IIA on thermal hyperalgesia in a mouse model of bone cancer-pain. Spinal IL
      1beta, IL-6, TNF-alpha expression levels were analyzed. C3H/HeNCrlVr male mice
      were assigned to groups that either received dose-dependent injections of
      Tanshinone IIA, or the DMSO + Sham, Tanshinone IIA + Sham, DMSO + Tumor, and
      Control groups. Paw withdrawal thermal latency (PWTL) was measured with a radiant
      heat stimulus and mRNA expression levels were determined using real-time PCR.
      Fourteen days post-injection, PWTL in the DMSO + Tumor group was lower than that
      in the controls (P < 0.05). Twenty-one days post-injection, compared with the
      Control group, there was no significant difference in PWTL and IL-1beta, IL-6,
      and TNF-alpha expression levels between the Tanshinone IIA + Sham and DMSO + Sham
      groups (P > 0.05). PWTL in the DMSO + Tumor group was significantly lower than
      the Control group (P < 0.05), while the expression levels of IL-1beta, IL-6, and
      TNF-alpha were significantly higher than controls. Compared with the DMSO + Tumor
      group, PWTLs were higher in the Tanshinone IIA - 20-MUg and 40-MUg groups, while
      expression levels of IL-1beta, IL-6, and TNF-alpha were significantly lower (P <
      0.05). These measures were not significantly different between the Tanshinone IIA
      10 MUg and the DMSO + Tumor groups (P > 0.05). In conclusion, Tanshinone IIA may
      inhibit the release of inflammatory cytokines, such as, IL-1 beta, IL-6 alpha,
      TNF-alpha.

PMID- 25867361
TI  - Post-surgical treatment of a patient with ectopic pheochromocytoma.
AB  - We report here the course and treatment of a patient with ectopic
      pheochromocytoma. The patient was cured after treatment with respiratory and
      circulatory support, multiple-organ protection, and continuous renal replacement
      therapy (CRRT) for approximately 2 weeks. After misdiagnosis, a patient with
      ectopic pheochromocytoma who is being treated should undergo aggressive fluid
      supplementation and CRRT instead of central venous pressure measurement, which
      has limited value in guiding fluid supplementation. The main priority is
      maintaining hypotension. Hypertension may be controlled with rapid-acting agents.
      A good outcome can be anticipated for patients who undergo comprehensive
      intensive care unit therapy. 

PMID- 25867362
TI  - Meta-analysis of differentially expressed genes in autism based on gene
      expression data.
AB  - The purpose of this study was to identify differentially expressed (DE) genes and
      biological processes associated with changes in gene expression in autism. We
      performed a meta-analysis using new publicly available Gene Expression Omnibus
      (GEO) datasets of autism. We performed Gene Ontology (GO) enrichment analyses and
      pathway analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG). Ten
      GEO datasets, including 364 cases and 248 controls, were available for the meta
      analysis. We identified 3105 genes that were consistently DE in autism (1425
      upregulated and 1680 downregulated genes). We also found that 7 genes were
      associated with phospholipase A2 (PLA2), including LYPLA2P1, PLA2G4D, PNPLA2,
      LYPLA2, PLA2G6, PLA2G7, and PLA2G5. We found GO terms for molecular functions
      significantly enriched in structural constituent of ribosome (GO: 0003735, P =
      1.87-E06) and transcription regulator activity (GO: 0030528, P = 8.86E-04), while
      for biological processes, the enriched GO terms were involved in translational
      elongation (GO: 0006414, P = 1.74E-12) and the response to cytokine stimuli (GO:
      0034097, P = 2.76E-05). The most significant pathway in our KEGG analysis was the
      ribosome pathway (P = 7.90E-12). Our meta-analysis identified genes that were
      consistently DE and biological pathways associated with gene expression changes
      in autism.

PMID- 25867363
TI  - Increased human epididymis protein 4 in benign gynecological diseases complicated
      with chronic renal insufficiency patients.
AB  - We examined the serum concentration of human epididymis protein (HE4) in patients
      with benign gynecological diseases complicated with chronic renal deficiency and
      its significance in the differential diagnosis of benign and malignant
      gynecological diseases. Serum HE4 and cancer antigen 125 concentrations were
      detected by chemiluminescence. Clinically or pathologically confirmed
      gynecological diseases were grouped and retrospectively analyzed, including 50
      cases of gynecological benign diseases, 35 cases of non-mucinous epithelial
      ovarian carcinoma, 36 cases of endometrial adenocarcinoma, 15 cases of
      gynecological benign diseases patients complicated with chronic renal deficiency,
      15 cases of gynecological diseases without chronic renal deficiency, and 30
      normal controls. Serum HE4 values in the ovarian cancer group, endometrial cancer
      group, gynecological benign diseases with chronic renal deficiency group, and
      chronic renal deficiency group were significantly increased compared with the
      benign gynecological diseases and normal control groups, showing a significant
      difference (P < 0.001). A comparison of 4 groups with high HE4 showed that the
      HE4 level in the 2 groups with renal deficiency were higher than those in the
      ovarian cancer and endometrial cancer groups, but the difference was not
      significant (P > 0.05); there was no significant difference between 2 groups with
      renal deficiency (P > 0.05). Serum concentration of HE4 was high in patients with
      chronic renal deficiency, which should be distinguished during differential
      diagnosis of gynecological benign and malignant tumors in patients with chronic
      renal deficiency to avoid misdiagnosis.

PMID- 25867364
TI  - Stimulation of dendritic cell maturation and induction of apoptosis in lymphoma
      cells by a stable lectin from buckwheat seeds.
AB  - The present study aims to purify and characterize lectin from tartary buckwheat
      seeds and study its properties as well as biological activities to determine its
      possible biomedical applications in promoting maturation and proliferation of
      peripheral blood DCs derived from healthy donors and to study the effect of
      inducing apoptosis in human leukemia U937 cells. A novel tartary buckwheat lectin
      (TBL) protein, purified from tartary buckwheat seeds, showed a single band with a
      molecular mass of 65 kDa in SDS-PAGE. The purified TBL hemagglutinated both human
      and animal erythrocytes and showed preference for blood type O and the rabbit
      blood type. TBL is active at up to 60 degrees C, and it is acid- and alkali
      stable. TBL (25 MUg/mL) combined with 5 x 10(-5) M rhIL-4 promotes maturation and
      proliferation of peripheral blood dendritic cells (DCs), which is stronger than
      that promoted by rhTNF-alpha (20 ng/mL). Exposure of DCs to 50 MUg/mL TBL for 48
      h resulted in extensive upregulation of maturation markers CD83 and CD40. These
      TBL-DCs were capable of producing several pro-inflammatory cytokines such as
      interleukin-10 (IL-10) and interleukin-12 (IL-12). The results of the treatment
      of human leukemia U937 cells with TBL in doses of 12.5, 25, 50, and 100 MUg/mL
      showed that tartary buckwheat-derived lectin induces apoptosis in a dose
      dependent manner. Our results encourage the use of tartary buckwheat and tartary
      buckwheat-derived lectins as immunopotentiating foods, targeted to strengthen
      immune responses and display a potential dietary supplement for cancer
      prevention.

PMID- 25867365
TI  - Establishment of the genomic in situ hybridization (GISH) technique for analysis
      in interspecific hybrids of Passiflora.
AB  - The genomic in situ hybridization (GISH) technique was applied to Passiflora
      interspecific F1 HD13-133 hybrids (Passiflora sublanceolata x Passiflora foetida)
      and HD15-101 (Passiflora gardineri x Passiflora gibertii), and the backcrossed
      hybrids (BC1) HD18-106 and HD18-113 (Passiflora sublanceolata x HD13-133). GISH
      was performed using genomic probes prepared with the DNA from the paternal
      genitor, whereas the maternal DNA was used as blocking DNA and employed at
      various concentrations (20X, 40X, 60X, and 100X) in relation to the probe
      concentration. At the same time, GISH was applied with the use of simultaneous
      probes from both genomes, paternal and maternal, that were detected with avidin
      FITC and anti-digoxigenin-rhodamine, respectively. Both methodologies allowed the
      distinguishing of the maternal and paternal genomes, thus confirming the hybrid
      nature of all the analyzed genotypes. Furthermore, the presence of recombinant
      chromosomes in BC1 hybrids revealed the occurrence of meiotic recombination in
      HD13 hybrids. This application of the GISH technique is an important step towards
      genomic analyses of Passiflora hybrids: it can broaden the phylogenetic and
      evolutionary studies of the genus and, at the same time, contribute to breeding
      programs.

PMID- 25867366
TI  - Genome-wide identification, classification, and analysis of heat shock
      transcription factor family in Chinese cabbage (Brassica rapa pekinensis).
AB  - Chinese cabbage (Brassica rapa ssp. pekinensis) is one of the most important
      vegetable crops grown worldwide, and various methods exist for selection,
      propagation, and cultivation. The entire Chinese cabbage genome has been
      sequenced, and the heat shock transcription factor family (Hsfs) has been found
      to play a central role in plant growth and development and in the response to
      biotic and abiotic stress conditions, particularly in acquired thermotolerance.
      We analyzed heat tolerance mechanisms in Chinese cabbage. In this study, 30 Hsfs
      were identified from the Chinese cabbage genome database. The classification,
      phylogenetic reconstruction, chromosome distribution, conserved motifs,
      expression analysis, and interaction networks of the Hsfs were predicted and
      analyzed. Thirty BrHsfs were classified into 3 major classes (class A, B, and C)
      according to their structural characteristics and phylogenetic comparisons, and
      class A was further subdivided into 8 subclasses. Distribution mapping results
      showed that Hsf genes were located on 10 Chinese cabbage chromosomes. The
      expression profile indicated that Hsfs play differential roles in 5 organs in
      Chinese cabbage, and likely participate in the development of underground parts
      and regulation of reproductive growth. An orthologous gene interaction network
      was constructed, and included MBF1C, ROF1, TBP2, CDC2, and HSP70 5 genes, which
      are closely related to heat stress. Our results contribute to the understanding
      of the complexity of Hsfs in Chinese cabbage and provide a basis for further
      functional gene research.

PMID- 25867367
TI  - Calpain-10 gene polymorphisms and risk of type 2 diabetes mellitus in Mexican
      mestizos.
AB  - The calpain-10 gene is expressed primarily in tissues important in glucose
      metabolism; thus, some of its polymorphisms have been associated with type 2
      diabetes. In this study, we examined the association between the calpain-10
      single-nucleotide polymorphism (SNP)-43, SNP-19, and SNP-63 and type 2 diabetes
      in Mexican mestizos. We included 211 patients and 152 non-diabetic subjects.
      Polymerase chain reaction was used to identify alleles. We compared allele,
      genotype, haplotype, and diplotype frequencies between both groups and used the
      chi-square test to calculate the risk. The allele frequency of SNP-43 allele 1
      was 70% in controls and 72% in patients; the GG, GA, and AA genotype frequencies
      were 48.7, 42.8, and 8.5% in controls and 51.2, 41.7, and 7.1% in patients,
      respectively. For SNP- 19, the prevalence of allele 1 (2R) was 32% in controls
      and 39% in patients. In controls, homozygosity (2R/2R) was 10.5%, heterozygosity
      was 42.8%, and 3R/3R was 46.7%; in cases, these values were 13.3, 50.7, and
      36.0%, respectively. For SNP-63, the frequency of allele 1 was 87% in controls
      and 83% in patients; genotype frequencies in controls were 75.7% (CC), 23% (CT),
      and 1.3% (TT), and were 69.7, 27.5, and 2.8%, respectively for the cases.
      Genotype distributions were consistent with Hardy-Weinberg equilibrium. No
      significant intergroup differences for allele, genotype, haplotype, or diplotype
      frequencies were observed. We found no association between these polymorphisms
      and diabetes. However, our sample size was small, so the role of calpain-10 risk
      alleles should be further examined.

PMID- 25867368
TI  - Abnormal gene expression profile reveals the common key signatures associated
      with clear cell renal cell carcinoma: a meta-analysis.
AB  - The aims of this study were to identify the common gene signatures of clear cell
      renal cell carcinoma (CCRCC), and to expand the respective protein-protein
      interaction networks associated with CCRCC regulation. For the latter, we
      utilized multiple gene expression data sets from the National Center for
      Biotechnology Information (NCBI) Gene Expression Omnibus (GEO), with which we
      could analyze the aberrant gene expression patterns at the transcriptome level
      that distinguish cancer from normal samples. We obtained the GSE781 and GSE6344
      clear cell renal cell carcinoma gene expression datasets from GEO, which
      contained a total of 37 cancer and 37 normal samples. Subsequent R language
      analysis allowed identification of the differentially expressed genes. The genes
      that exhibited significant up or downregulation in cancers were entered into the
      Database for Annotation, Visualization, and Integrated Discovery to perform
      analysis of gene functional annotations, resulting in the generation of two
      protein-protein interaction networks that included the most significantly up or
      downregulated genes in CCRCC. These allowed us to identify the key factor genes,
      which could potentially be utilized to separate cancer versus normal samples. The
      differentially regulated genes are also highly likely to be functionally
      important regulatory factors in renal cell carcinoma: cell functions showing
      enrichment of these genes include amine biosynthetic and vitamin metabolic
      processes, ion binding, extracellular transport function, and regulation of
      biosynthesis. Together, the results from our study offer further reason to pursue
      diagnosis and therapy of CCRCC at the molecular level.

PMID- 25867369
TI  - Association between growth differentiation factor-15 and chronic heart failure in
      coronary atherosclerosis patients.
AB  - We explored the association between plasma growth differentiation factor 15 (GDF
      15) levels and chronic heart failure (CHF) in coronary heart disease patients. We
      measured plasma GDF-15 and N-terminal pro-B-type natriuretic peptide (NT-proBNP)
      levels in 269 untreated coronary heart disease patients (98 with CHF, 84 without
      CHF, and 87 control patients) using an enzyme-linked immunosorbent assay. All
      subjects were examined by echocardiography and left ventricular ejection
      fraction. We found that plasma GDF-15 levels in coronary atherosclerosis patients
      with CHF [median 1622.48 (25-75th percentile: 887.53-1994.93) ng/L] were higher
      than those in coronary atherosclerosis patients without CHF [944.99 (856.12
      999.78) ng/L] and control patients (P < 0.05). NT-proBNP showed the same trend as
      GDF-15. We also used the New York Heart Association functional classification to
      subgroup CHF patients and found that the GDF-15 level was higher in all subgroup
      patients with CHF. After adjusting for covariates, plasma GDF-15 levels were
      found to be positively related to NT-proBNP (r = 0.861, P < 0.001) and negatively
      related to left ventricular ejection fraction (r = -0.936, P < 0.001).
      Furthermore, receiver operating characteristic curves of GDF-15 and NT-proBNP
      were constructed and the area under the curve for the untransformed GDF-15 and NT
      proBNP was 0.804 and 0.795, respectively. Plasma GDF-15 levels and NT-proBNP are
      associated with CHF in coronary atherosclerosis patients and can be used as
      biomarkers.

PMID- 25867370
TI  - Correlation of spicule sign on computed tomography scans with peripheral lung
      cancers associated with interstitial lung disease and chronic obstructive
      pulmonary disease.
AB  - The objective of this study was to investigate the correlation between spicular
      signs on computed tomography (CT) scans and peripheral lung cancer (PLC) that is
      associated with interstitial lung disease (ILD) and chronic obstructive pulmonary
      disease (COPD). We analyzed clinical data from 96 PLC cases and grouped patients
      based on whether they had interstitial pneumonia into either ILD/COPD group or
      non-ILD/COPD group. The occurrence rate of spicule sign was 90.3% in the ILD/COPD
      group and 61.8% in the non-ILD/COPD group, respectively. There was a significant
      difference between these groups (P < 0.05). There were no significant differences
      in the occurrence rate of spicular signs among patients with different
      pathological types of PLC. The severity of ILD affected the spicular morphology
      on CT scans directly. There was a significant correlation between the appearance
      of spicule sign on CT scans and PLC that was associated with ILD/COPD. 

PMID- 25867371
TI  - Association of SSR markers with contents of fatty acids in olive oil and genetic
      diversity analysis of an olive core collection.
AB  - The purpose of this research was to characterize an olive core collection using
      some agronomic characters and simple sequence repeat (SSR) markers and to
      determine SSR markers associated with the content of fatty acids in olive oil.
      SSR marker analysis demonstrated the presence of a high amount of genetic
      variation between the olive cultivars analyzed. A UPGMA dendrogram demonstrated
      that olive cultivars did not cluster on the basis of their geographic origin.
      Fatty acid components of olive oil in these cultivars were determined. The
      results also showed that there was a great amount of variation between the olive
      cultivars in terms of fatty acid composition. For example, oleic acid content
      ranged from 57.76 to 76.9% with standard deviation of 5.10%. Significant
      correlations between fatty acids of olive oil were observed. For instance, a very
      high negative correlation (-0.812) between oleic and linoleic acids was detected.
      A structured association analysis between the content of fatty acids in olive oil
      and SSR markers was performed. STRUCTURE analysis assigned olive cultivars to two
      gene pools (K = 2). Assignment of olive cultivars to these gene pools was not
      based on geographical origin. Association between fatty acid traits and SSR
      markers was evaluated using the general linear model of TASSEL. Significant
      associations were determined between five SSR markers and stearic, oleic,
      linoleic, and linolenic acids of olive oil. Very high associations (P < 0.001)
      between ssrOeUA-DCA14 and stearic acid and between GAPU71B and oleic acid
      indicated that these markers could be used for marker-assisted selection in
      olive.

PMID- 25867372
TI  - A C-type lectin fold gene from Japanese scallop Mizuhopecten yessoensis, involved
      with immunity and metamorphosis.
AB  - C-type lectins are a superfamily of Ca(2+)-dependent carbohydrate-recognition
      proteins that are well known for their participation in pathogen recognition and
      clearance. In this study, a putative C-type lectin fold (MyCLF) gene was
      identified from the Japanese scallop Mizuhopecten yessoensis. The full-length of
      MyCLF was 645 bp, encoding a polypeptide of 167 amino acids. MyCLF carried a
      signal peptide of 20 amino acid residues, and a single carbohydrate recognition
      domain, having relatively high amino acid sequence conservation with C-type
      lectins reported for other bivalves. The expression of MyCLF mRNA transcripts in
      adult tissues, after bacterial challenge and during different developmental
      stages was determined using real-time quantitative RT-PCR. MyCLF was mainly
      distributed in the mantle, gill, and kidney. The expression of MyCLF clearly
      increased 3 h after Vibrio anguillarum challenge, and dropped to a minimum level
      after 9 h compared to the control group. During embryonic development, the
      expression level increased in the gastrulae, trochophore and early D-shaped
      larvae, decreased in D-shaped larvae, and then increased hundreds of times in
      metamorphosing larvae. The results suggested that MyCLF was involved in an immune
      response and it may play important roles during the metamorphosis phase of M.
      yessoensis. 

PMID- 25867373
TI  - Upregulation of salivary alpha2 macroglobulin in patients with type 2 diabetes
      mellitus.
AB  - We investigated the expression of salivary alpha2-macroglobulin (alpha2-MG) in
      patients with type 2 diabetes mellitus (T2DM) to investigate its value for
      predicting damage to the salivary glands. A total of 116 patients with T2DM and
      60 patients with impaired fasting glucose (IFG) were included in this study.
      Sixty health volunteers were enrolled as a control group. Unstimulated saliva was
      collected at 8 a.m. prior to breakfast. Expression of alpha2-MG was determined
      using an enzyme-linked immunosorbent assay. The correlation between salivary
      alpha2-MG, serum alpha2-MG, and concentration of fasting glucose was analyzed
      using Pearson correlation analysis. No significant difference was observed in the
      expression of serum alpha2-MG in the T2DM group, IFG group, and control group (P
      > 0.05). Compared with the control group and IFG group, a statistical difference
      was observed in the salivary alpha2-MG in the T2DM group (P < 0.01). No
      statistical difference was observed in the salivary alpha2-MG in the IFG group
      compared with the control group (P > 0.05). In the patients with T2DM, a close
      correlation was identified in the expression of serum alpha2-MG and salivary
      alpha2-MG (r = 0.52, P < 0.01). A poor correlation was identified between
      salivary alpha2-MG and blood sugar level (r = -0.12, P = 0.199). The expression
      of salivary alpha2-MG showed a remarkable increase in T2DM patients, which may be
      associated with functional disorders of the salivary gland.

PMID- 25867374
TI  - Isolation, partial characterization, and cloning of an extracellular chitinase
      from the entomopathogenic fungus Verticillium lecanii.
AB  - The entomopathogenic fungus Verticillium lecanii is a well-known biocontrol agent
      of fungal phytopathogens, as well as insect pests. A 42-kDa chitinase belonging
      to family 18 of the glycosyl hydrolases was isolated and partially characterized.
      Chitinase was purified using successive column chromatography on phenyl
      sepharose, DEAE-sepharose, and CM-sepharose. The enzyme showed the highest
      activity at 40 degrees C and pH 4.6. Enzyme activity was strongly activated in
      the presence of Mg(2+). The purified enzyme showed inhibitory activity of spore
      germination against several plant pathogens, particularly Fusarium moniliforme.
      The genomic DNA and cDNA sequences were resolved by polymerase chain reaction
      amplification and sequencing. Protein modeling and comparative investigation of
      different chitinase amino acids showed that chitinases are conserved in parasitic
      fungi. 

PMID- 25867376
TI  - Molecular identity of ramie germplasms using simple sequence repeat markers.
AB  - DNA identity is highly effective and efficient for distinguishing crop varieties
      regardless of their phenotypic similarities. To establish DNA identity in ramie,
      21 simple sequence repeat primers were amplified in 108 accessions of domestic
      and exotic ramie germplasms. Sixty polymorphic bands were obtained, with an
      average of 2.9 bands per locus and 2-8 band types per primer locus (average of
      5.19 band types). The Simpson's diversity index of the 21 simple sequence repeat
      loci ranged from 0.158 to 0.808 with an average of 0.612. There was large
      difference in the specific index in the germplasm tested, from 44.082 to 218.163,
      with an average of 83.620. Based on allele band type, 8 primer pairs were
      selected for DNA fingerprinting of the 108 genotypes. The combination of the 8
      primer pairs were found to be very effective for distinguishing these genotypes,
      indicating that they can be used in the molecular DNA identity of ramie. 

PMID- 25867375
TI  - Identification, molecular characterization, and tissue expression of parathyroid
      hormone-related protein gene (PTHrP) from water buffalo (Bubalus bubalis).
AB  - Parathyroid hormone-related protein (PTHrP) is involved in the deposition of milk
      calcium in mammal lactation, but its role in buffalo is unclear. In this study,
      the full-length coding sequence of the water buffalo PTHrP gene was first
      isolated using reverse transcription-polymerase chain reaction. The protein was
      then subjected to molecular characterization using bioinformatic methods, and the
      tissue expression pattern was further assayed by semi-quantitative reverse
      transcription polymerase chain reaction. The water buffalo PTHrP gene contains an
      open reading frame of 534 base pairs encoding a polypeptide of 177 amino acid
      residues, a theoretical molecular weight of 20.32 kDa, and an isoelectric point
      of 10.00. In addition, water buffalo PTHrP was predicted to contain a signal
      peptide, a typical hydrophobic region with no hydrophobic transmembrane regions,
      and to exert its function in the cell nucleus. A conserved domain of parathyroid
      superfamily from amino acids 34-114 was observed in the polypeptide. Sequence
      comparison and the phylogenetic analysis showed that the sequence of the water
      buffalo PTHrP protein shared high homology with that of other mammals,
      particularly cattle and goat. Among the 16 tissues examined, the PTHrP gene was
      only expressed in adipose tissue, placenta, uterine wall, hypophysis, and mammary
      gland tissue, but gene expression levels were higher in the uterus wall and
      adipose tissue. The results of this study suggest that the PTHrP gene plays an
      important role in the deposition of milk calcium of water buffalo. 

PMID- 25867377
TI  - Correlation between neuronal antibodies and limbic encephalitis in Chinese Han
      subjects.
AB  - A variety of anti-neuronal cell membrane antibodies such as voltage-gated
      potassium channel antibody, N-methyl-D-aspartate-2B-antibody, and glutamic acid
      decarboxylase antibody, are correlated with limbic encephalitis (LE). In this
      study on patients with LE, the clinical manifestations, psychology Wechsler Adult
      Intelligence Scale, cerebrospinal fluid, electrophysiology, magnetic resonance
      imaging, and anti-immune therapy were studied and immunological determination was
      conducted; it was found that patients of Chinese Han nationality showed 2 types
      of clinical manifestations: simple and complex. Lesions could also be divided
      into focal and scalable lesions, and the clinical manifestations and lesions
      scopes were associated with various antibodies and antibody types. The prognosis
      may improve if early diagnosis is conducted and early anti-immune therapy is
      implemented in LE patients. 

PMID- 25867378
TI  - Estimation of the growth curve and heritability of the growth rate for giant
      panda (Ailuropoda melanoleuca) cubs.
AB  - Giant panda cubs have a low survival rate during the newborn and early growth
      stages. However, the growth and developmental parameters of giant panda cubs
      during the early lactation stage (from birth to 6 months) are not well known. We
      examined the growth and development of giant panda cubs by the Chapman growth
      curve model and estimated the heritability of the maximum growth rate at the
      early lactation stage. We found that 83 giant panda cubs reached their maximum
      growth rate at approximately 75-120 days after birth. The body weight of cubs at
      75 days was 4285.99 g. Furthermore, we estimated that the heritability of the
      maximum growth rate was moderate (h(2) = 0.38). Our study describes the growth
      and development of giant panda cubs at the early lactation stage and provides
      valuable growth benchmarks. We anticipate that our results will be a starting
      point for more detailed research on increasing the survival rate of giant panda
      cubs. Feeding programs for giant panda cubs need further improvement. 

PMID- 25867379
TI  - Cloning and characterization of peanut allene oxide cyclase gene involved in salt
      stressed responses.
AB  - In this study, the full-length cDNA encoding allene oxide cyclase (AhAOC) was
      isolated from peanut (Arachis hypogaea L.). The deduced amino acid sequence of
      AhAOC showed high homology with other plant AOCs. The transcript of AhAOC was
      found to be abundantly expressed in roots. Expression analysis demonstrated that
      AhAOC was induced by abscisic acid, methyl-jasmonic acid, salicylic acid,
      salinity, polyethylene glycol, and cold stresses, particularly by high salinity.
      Overexpression of AhAOC in rice increased root elongation and plant height
      compared with expression in control plants and conferred tolerance against
      salinity. Thus, the AhAOC gene may play an important role in increasing the
      expression of transcription factors (MYB2 and OsONAC045) and functional genes
      (DREB1F and LEA3) in transgenic rice under salt stress as well as improve stress
      tolerance through the accumulation of compatible solutes (proline and soluble
      sugar). The AhAOC gene is a potential resource for enhancing salt tolerance in
      crop species.

PMID- 25867380
TI  - Mutations in the FGFR2 gene in Mexican patients with Apert syndrome.
AB  - Apert syndrome (AS) is a frequent acrocephalosyndactyly, with autosomal dominant
      inheritance. AS has been associated with mutations in fibroblast growth factor
      receptor 2 (FGFR2), and approximately 99% of cases show 2 of the frequent
      mutations located in exon IIIa (Ser252Trp or Pro253Arg). The purpose of the
      present study was to describe the mutations in exon IIIa of FGFR2 in Mexican AS
      patients and the relationships with clinical features. Exon IIIa of FGFR2 from 6
      AS patients was amplified by polymerase chain reaction. Mutations in exon IIIa of
      the FGFR2 gene were identified by digestion with the restriction endonuclease
      Bstx1 and polyacrylamide gel electrophoresis. PCR fragments were cloned into the
      PCR 2.1 vector, and both DNA strands were sequenced using the T7 promoter and M13
      universal cloning region oligonucleotides. Sequence alignment was performed using
      the MEGA software version 5. The patients' major clinical features included
      craniosynostosis, hypertelorism, proptosis, otitis media, midfacial hypoplasia,
      rhizomelic shortening, and hyperhidrosis. Mutation S252W was present in 4
      patients, while the other 2 patients had P253R. In conclusion, either S252W or
      P253R mutations were present independently in AS patients; however, the 2
      mutations were not found together. None of the clinical features were associated
      with any of the mutations, suggesting that other mutations may be involved in the
      development of this syndrome.

PMID- 25867381
TI  - Preliminary study of the effects of beta-elemene on MCF-7/ADM breast cancer stem
      cells.
AB  - We examined expression differences in breast cancer stem cells (BCSCs) of the
      doxorubicin-resistant breast cancer cell line MCF-7/ADM and doxorubicin-sensitive
      cell line MCF-7/S. The effects of Chinese medicine beta-elemene on BCSCs and
      resistance protein expression were determined. The serum-free cell culture method
      was used for cell culture, and morphology was observed to determine the rate of
      cell sphere formation. Reverse transcription-polymerase chain reaction was used
      to detect breast cancer resistance protein (BCRP) and P-glycoprotein (P-gp) gene
      expression. Flow cytometry was used to determine BCRP- and P-gp-positive cell
      rates and CD44 + CD24-/low cell ratios. Morphological observation and gene
      amplification showed that compared with MCF-7/S cells, the serum-free cell sphere
      forming rate and P-gp and BCRP gene expression levels were higher in MCF-7/ADM
      cells. Flow cytometry results showed that P-gp and BCRP protein expression in MCF
      7/ADM cells was 77.78 +/- 9.55% and 32.33 +/- 5.12%, respectively, and the CD44 +
      CD24-/low cell rate was 64.79 +/- 11.78%, which were all significantly higher
      than those in MCF-7/S cells (3.97 +/- 1.51, 14.26 +/- 2.51, 18.79 +/- 3.28%; P <
      0.05). beta-elemene significantly decreased the serum-free cell sphere-forming
      rate in MCF-7/ADM cells and BCRP and P-gp gene/protein expression (P < 0.01). The
      proportion of CD44 + CD24-/low cells was reduced. MCF-7/ADM highly expressed the
      drug-resistant proteins BCRP and P-gp, which can be used for long-term in vitro
      culture and as a seed cell for studies of BCSCs. beta-elemene can inhibit BCSC
      and the sphere-forming rate in MCF-7/ADM cells and reduce BCRP expression.

PMID- 25867382
TI  - A multi-center study on the prophylactic application of antibiotics in aseptic
      operations.
AB  - To understand the application of antibacterial agents in aseptic operations and
      to provide evidence for their rational use and management, the antibiotic use
      statuses of six types of aseptic operations (306 cases from 4 tertiary hospitals)
      were retrospectively analyzed. Of 312 patients, 306 (65.08%) were treated with
      antibacterial agents in the perioperative period. Four categories of antibiotics
      including cephalosporins, penicillins, nitroimidazoles, and fluoroquinolones were
      administered (descending sequence). Administration time: preoperative >2 h, 15
      cases; preoperative 0.5-2 h, 20 cases; postoperative: 265 cases. Drug withdrawal
      time: postoperative 1-3 days: 33 cases; 3-7 days: 255 cases; 7-15 days: 12 cases.
      The prophylactic use of antibacterial agents in aseptic operations suffers from
      non-strict mastered medication indication, improper drug selection, aimless drug
      combinations, inappropriate administration timing, and over long medication
      duration. 

PMID- 25867383
TI  - Effect of the mixture of bone marrow mesenchymal stromal cells and annulus
      fibrosus cells in repairing the degenerative discs of rabbits.
AB  - The aims of this study were to investigate the effect of a mixture of bone marrow
      mesenchymal stem cells (BMSCs) and annulus fibrosus cells (AFCs) in repairing the
      degenerative discs of rabbits, and to provide an experimental basis for its
      clinical application. BMSCs from rabbits were cultured in vitro and mixed with
      AFCs. The animal model of degenerative intervertebral disc was built by
      aspirating the nucleus pulposus (L3-4, L4-5, L5-6, and L6-7) through a
      posterolateral approach. Mixtures of BMSCs and AFCs (group A), BMSCs alone (B),
      or saline (C) were injected into test discs, and changes evaluated by plain
      radiographs, magnetic resonance imaging, and histology. After two weeks, each
      group showed typical internal disc disruption; stenosis of the intervertebral
      space, weakening T2 disc signal, decreased disc height and expression of type II
      collagen and glycosaminoglycan, and fibrosis of the nucleus pulposus. After cell
      transplantation, the disc heights in groups A and B were regained; however, they
      continued to decrease in group C. The transplanted cells survived in the discs,
      proliferated after transplantation, and produced copious matrix. Macroscopic and
      histological evaluations confirmed structural and nuclear preservation in cell
      transplanted discs. The secretions and expressions of Type II collagen and
      glycosaminoglycan in group A were statistically significant higher than those in
      group B (Type II collagen, group A 141.6 +/- 5.87, group B 139.8 +/- 8.65, P =
      0.004; glycosaminoglycan, group A 3.008 +/- 0.35, group B 2.94 +/- 0.29, P =
      0.003). Expression of type II collagen and glycosaminoglycan was significantly
      greater in group A than group B. Therefore, co-transplantation of BMSCs and AFCs
      can restore the extracellular matrix, making this approach superior to
      transplantation of BMSCs alone, which may be beneficial for the therapy of
      intervertebral disc degeneration.

PMID- 25867384
TI  - Expression and tyrosine phosphorylation of sp32 regulate the activation of the
      boar proacrosin/acrosin system.
AB  - The current study investigated the relationship between the level of expression
      and tyrosine phosphorylation of the sperm protein 32 (sp32) and the activation of
      the boar proacrosin/acrosin system. The acrosomal membrane proteins of boar sperm
      for use in different treatment experiments (i.e., fresh sperm, freezing and
      thawing, capacitation, and acrosome reaction) were separated, stained by
      Coomassie brilliant blue, and analyzed using sodium dodecyl sulfate
      polyacrylamide gel electrophoresis and western blot. The results showed that
      there were differences in the expression level of sp32 among capacitated, frozen
      thawed, and post acrosomal reaction sperms. sp32 expression was higher and
      significantly higher in capacitated and post-acrosomal reaction sperms than in
      frozen-thawed sperms and fresh semen, respectively. The level of sp32 tyrosine
      phosphorylation was significantly different between the frozen-thawed sperms and
      sperms in the other experimental groups. However, bands with molecular masses of
      38 to 170 ku in the fresh semen group were more noticeable, indicating that large
      acrosomal membrane proteins underwent modification and degradation during
      capacitation and the acrosomal reaction. As a proacrosin binding protein, sp32
      shows upregulated expression and increase in tyrosine phosphorylation levels
      during the activation of the boar proacrosin/acrosin system. 

PMID- 25867385
TI  - Evaluation of reference genes for RT-qPCR studies in the leaves of rice seedlings
      under salt stress.
AB  - To obtain accurate and reliable results for the expression of genes of interest
      using quantitative real-time polymerase chain reaction (RT-qPCR) techniques, it
      is necessary to normalize the data by comparing them to constitutive genes that
      exhibit uniform expression levels under experimental conditions. In this study,
      the stability of expression was evaluated for the following ten candidate
      reference genes in rice leaves (Oryza sativa L.) from the BRS Bojuru and BRS
      Ligeirinho genotypes that were subjected to salt stress (150 mM): actin 11
      (ACT11), beta-tubulin (beta-TUB), eukaryote elongation factor 1-alpha (Eef-1),
      eukaryotic initiation factor 4-alpha (eIF-4-alpha), E2 ubiquitin-conjugating
      enzyme (UBC-E2), ubiquitin 5 (UBQ5), ubiquitin 10 (UBQ10), glyceraldehyde-3
      phosphate dehydrogenase (GAPDH), TIP41-like, and cyclophilin. The stability of
      expression for the aforementioned genes was then compared to that of three LTP
      genes using UBQ10, Eef-1, and eIF-4-alpha as references. After analyzing the
      expression levels using analysis of variance tests, the results indicated that
      UBQ10 was the most stable in all treatments (M = 0.404 and SV = 0.327).
      Furthermore, the eIF-4-alpha, TIP41-like, and cyclophilin genes exhibited the
      highest total coefficient of variation (CV = 269, 169.2, 179.2, respectively),
      which signifies that they exhibited the least stable expression. The expression
      levels of each candidate gene (LTP7, LTP10, and LTP13) were in contrast to the
      reference genes. Therefore, we concluded that UBQ10 is the best reference gene
      for RT-qPCR reactions under the experimental conditions. The expression analysis
      of LTP7, LTP10, and LTP13 confirmed the importance of validating reference genes
      to achieve accurate RT-qPCR results.

PMID- 25867386
TI  - Identification of the transcriptionally active cytochrome P450 repertoire in
      Coffea arabica.
AB  - Cytochrome P450s (P450s) comprise a gene superfamily encoding enzymes that are
      involved in diverse plant metabolic pathways that produce primary and secondary
      metabolites such as phenylpropanoids, terpenoids, nitrogen-containing compounds,
      and plant hormones. They comprise one of the most diverse gene families in plant
      evolution. Although there are many studies that aim to characterize P450s in
      plants, there is no report on the characterization of this superfamily in Coffea
      arabica, where they might be related to plant tolerance to biotic and abiotic
      stresses, as well as aroma-related compounds. In this study, we report the
      characterization and annotation of 87 putative P450s from C. arabica obtained
      from the Brazilian Coffee Genome Project and describe their transcriptional
      pattern in different tissues and coffee organs. To validate our approach, we
      measured the transcriptional profile of the CaCYP81D8_1 gene by quantitative
      polymerase chain reaction in leaves, flowers, and fruits. This study is the first
      effort to present and analyze the P450 superfamily in C. arabica, which may
      assist in understanding the chemical diversity of coffee secondary metabolites.

PMID- 25867387
TI  - Detection of targets and their mechanisms for early diagnosis of traumatic deep
      vein thrombosis.
AB  - The purpose of this investigation was to identify targets for the early diagnosis
      and predictors of deep venous thrombosis (DVT) and the role of these targets in
      the formation of venous thrombosis. A model of DVT was constructed in rats.
      Thromboses and venous walls were sampled for reverse transcription polymerase
      chain reaction study, and blood was sampled for enzyme-linked immunosorbent assay
      studies. Vein endothelial cells were cultured to observe the effects of
      interleukin (IL)-17 on the expression of tissue plasminogen activator (t
      PA)/plasminogen activator inhibitor type 1 (PAI-1). IL-17 monoclonal antibody was
      used to study its effect on preventing the formation of DVT. One-hundred and
      twenty hours after the animal model was constructed, significant DVT started to
      form. Polymerase chain reaction tests showed that immediately after the model was
      created, the expression of IL-17 increased greatly, whereas the balance between t
      PA and PAI-1 was disrupted just before DVT formed. The increase of serum IL-17
      was positively related with the formation of DVT. Thus, the application of IL-17
      monoclonal antibody could reduce the formation of DVT in rats. IL-17 might be a
      target for the early diagnosis of DVT and should be further studied to assess its
      clinical value. 

PMID- 25867388
TI  - Genomic lesions and colorectal carcinogenesis: the effects of protein-calorie
      restriction and inulin supplementation on deficiency statuses.
AB  - The present study investigated the effects of restricting protein and calories
      and supplementation of inulin, a fiber comprising a linear type of polydisperse
      carbohydrates composed primarily of fructil-fructose bonds (beta-(2->1), on the
      deficiency statuses of animals in which genomic lesion development and colorectal
      carcinogenesis had been induced. This experiment involved adult male Swiss mice
      (N = 11/group). The experimental groups were as follows: Negative Control
      (vehicle), Positive Control, 1,2-dimethylhydrazine (DMH), Inulin, and Associate.
      DMH, which promoted colorectal cancer, was administered intraperitoneally in 4 20
      mg/kg body weight (bw) doses during a 2-week period; inulin was administered
      orally at a daily dose of 50 mg/kg bw. Each group was bifurcated; half of each
      group was fed a normal protein diet and the other half was fed a low-protein
      diet. The results indicated that a correlation existed between malnutrition and
      an increased frequency of genomic lesions but that malnutrition did not
      predispose animals to colorectal cancer development. Inulin exhibited genotoxic
      activity, which requires further investigation, and low anti-genotoxic activity.
      Moreover, inulin reduced the levels of intestinal carcinogenesis biomarkers in
      both malnourished and healthy animals. These data suggest that inulin holds
      therapeutic potential and is a strong candidate for inclusion among the
      functional foods used for cancer prevention in both properly nourished and
      malnourished individuals.

PMID- 25867389
TI  - Development and characterization of polymorphic microsatellite markers for
      Castanopsis hystrix (Fagaceae).
AB  - Castanopsis hystrix is one of the most important and dominant species in
      evergreen broad-leaved forests in subtropical China. However, the population of
      this species undergone severe decline because of deforestation over the past 2
      decades. For both conservation and forestry management, it is essential to
      develop molecular markers for C. hystrix. We identified 11 microsatellite loci in
      2 wild populations. The number of alleles ranged from 3-11, with an average of
      6.45 alleles per locus. The observed and expected heterozygosities ranged from
      0.640-0.960 and from 0.676-0.910, respectively. 

PMID- 25867390
TI  - Effect of ethyl methyl sulfonate concentration and different treatment conditions
      on germination and seedling growth of the cucumber cultivar Chinese long (9930).
AB  - We attempted to create a new germplasm of cucumber cultivar Chinese long (9930)
      using different doses of ethyl methyl sulfonate (EMS) to induce variability. We
      tested EMS concentration (0, 0.5, 1.0, 1.5, 2, 3% v/v) with post-treatment (0.1 M
      Na2S2O3 and water), EMS concentration (0, 0.5, 1.0, 1.5% v/v) over different
      treatment times (8, 16, 24 h), and EMS concentration (0, 0.5, 1.0, 1.5% v/v) with
      different treatment temperatures (20 and 28 degrees C). In all experiments with
      increasing EMS concentration, germination percent, index, and rate were
      decreased. After addition of stop solution (0.1 M Na2S2O3), post-treatment
      mutated seeds showed higher germination (84.44%) and rate (37.5%) than seeds
      treated with water (80 and 34.07%, respectively), while the germination index was
      high in seeds treated with water. At 20 degrees C, the germination index (4.13)
      and rate (56.25%) were affected to a greater extent than at 28 degrees C (7.68
      and 91.31%, respectively). Treatment times of 16 and 24 h showed similar results
      for germination percent and rate, while the germination index was decreased over
      time. There were significant differences in seedling height, fresh true leaf
      weight, seedling weight, and plant survival with increasing EMS concentration and
      time. Higher variations in the form of dwarf seedlings were recorded after
      treatment with 1.5% EMS for 24 h. Based on germination and morphological data, an
      EMS concentration of 1.5% for 24 h at 20 degrees C and post-treatment with stop
      solution (0.1 M Na2S2O3) efficiently caused mutation. 

PMID- 25867391
TI  - Inhibitor of signal transducer and activator of transcription 3 (STAT3)
      suppresses ovarian cancer growth, migration and invasion and enhances the effect
      of cisplatin in vitro.
AB  - The aim of the present study was to investigate the anti-ovarian cancer effect of
      the inhibitor of signal transducer and activator of transcription 3 (STAT3),
      WP1066. Western blot was used to detect the phosphorylation of STAT3 in ovarian
      cancer cell line SKOV3 and cisplatin-resistant ovarian cancer cell line
      SKOV3/DDP. MTT and colony-forming assays were performed to evaluate the viability
      and growth of ovarian cancer cells. The apoptosis of ovarian cancer cells was
      determined by flow cytometry. The wound healing assay and Transwell assay were
      performed to examine the migration and invasion of ovarian cancer cells. WP1066
      significantly inhibited the phosphorylation of STAT3 in SKOV3 and SKOV3/DDP
      cells. WP1066 treatment inhibited the proliferation and clonogenicity of both
      SKOV3 and SKOV3/DDP cells. After WP1066 treatment for 24 h, the apoptosis rates
      of SKOV3 and SKOV3/DDP cells were significantly increased compared with the
      control cells. After treatment with WP1066, the reduction of the wound gaps was
      significantly less in both SKOV3 and SKOV3/DDP cells. WP1066 also significantly
      inhibited the invasion capacity of SKOV3 and SKOV3/DDP cells compared with the
      control group. Treatment with WP1066 combined with cisplatin significantly
      increased proliferation inhibition and apoptosis in SKOV3 and SKOV3/ DDP cells
      compared with treatment with cisplatin alone. A synergistic action between WP1066
      and cisplatin on the proliferation and apoptosis of ovarian cancer cells was
      determined. In conclusion, inhibition of STAT3 may suppress the proliferation,
      migration and invasion, induce apoptosis and enhance the chemosensitivity of
      ovarian cancer cells, indicating that STAT3 is a new therapeutic target of
      ovarian cancer.

PMID- 25867392
TI  - Analysis of Fcgrt gene polymorphism in indigenous Chinese sheep and its
      association with colostrum IgG concentration.
AB  - The neonatal Fc receptor (FcRn) plays an important role in regulating IgG
      homeostasis in the body and passive protection to the offspring. Changes in FcRn
      expression levels caused by genetic polymorphisms of Fcgrt, which encodes FcRn,
      may lead to inter-individual differences in colostrum IgG levels in sheep. In
      this study, we sequenced the FcRn partial heavy chain from 179 sheep from
      Xinjiang Province, China, and detected the differences in colostrum IgG levels
      and Fcgrt genotypes to identify the correlation between the Fcgrt genotype and
      colostrum IgG levels in 4 sheep breeds. The DNA sequencing of a 680-bp fragment
      of the Fcgrt gene revealed various patterns depending on the single-strand
      conformation in the Suffolk breed. Sequencing analysis revealed a total of 3
      patterns, AA, BB, AB, in this fragment, among which the absence of AB and BB
      genotype acted as a marker for breed identification and characterization, while
      the AA genotype was shared by Suffolk and 3 other breeds. The only allele found
      in all 4 breeds was allele A, indicating that natural selection may be favoring
      the AB and BB genotypes in general and B allele in particular, as the colostrum
      IgG concentration was relatively higher in the Suffolk breed compared to the
      other 3 breeds. 

PMID- 25867393
TI  - Genetic diversity and population structure of Eucommia ulmoides Oliver, an
      endangered medicinal plant in China.
AB  - Eucommia ulmoides Oliver, one of the tertiary relict species found only in China,
      is the only extant species of Eucommiaceae. Using inter-simple sequence repeat
      (ISSR) and sequence-related amplified polymorphism (SRAP) markers, we studied the
      genetic diversity and population genetic structure of 187 accessions from 17 E.
      ulmoides populations throughout its main distribution in China. A total of 65
      bands were amplified using eight ISSR primers, of which 50 bands (76.9%) were
      polymorphic. Meanwhile, another 244 bands were observed using eight SRAP primer
      combinations and 163 (66.8%) of these were polymorphic. The analysis of molecular
      variation (AMOVA) indicated that 88.8 and 92.4% of the total variation resided
      within populations based on ISSR and SRAP analysis, respectively. Moreover, we
      found that the E. ulmoides populations were clustered into six distinct groups
      using ISSR and SRAP markers via the unweighted pair-group method (UPGMA).
      Furthermore, STRUCTURE analysis showed that these 17 populations could be
      classified into four groups using ISSR markers, but only two groups using SRAP
      markers. No significant relevancy was observed between genetic and geographic
      distances among the sampled populations. The results of this study support the
      view that exchange of seeds among local farmers plays an important role in
      shaping the present genetic distribution pattern. "Core collection" is suggested
      for genetic diversity conservation of E. ulmoides in China.

PMID- 25867394
TI  - Protective effect of proanthocyanidin against oxidative ovarian damage induced by
      3-nitropropionic acid in mice.
AB  - Oxidative stress, which poses a threat to reproductive health, causes many
      serious female reproductive diseases. In this study, we investigated whether
      proanthocyanidins (PC) have a protective effect against oxidative stress-induced
      ovarian damage. Forty female ICR mice were randomized into 4 groups: a control
      group, a control plus PC group, a 3-nitropropionic acid (3-NPA) group, and a 3
      NPA plus PC group. An ovarian oxidative stress model induced by 3-NPA was
      constructed using female ICR mice. After the animals were sacrificed, their
      ovaries were collected to measure reactive oxygen species (ROS) levels, the
      activities of superoxide dismutase (SOD) and catalase (CAT), and the mRNA
      expression levels of relevant granulosa cell apoptosis genes (Bcl-2, Bax, Bim,
      FasL, and caspase-3). We also conducted a histological evaluation of granulosa
      cell apoptosis and follicular atresia. The results showed that compared to the 3
      NPA group, ROS levels and activities of T-SOD and CAT in the 3-NPA plus PC group
      were significantly decreased (P < 0.05), while the ratio of Bcl-2 to Bax in the 3
      NPA plus PC group were significantly increased (P < 0.05). mRNA expression levels
      of Bim, FasL, and caspase-3 in the 3-NPA plus PC group were significantly
      decreased (P < 0.05), and the percentage of atretic follicles and granulosa cell
      apoptosis in the 3-NPA plus PC group was significantly decreased (P < 0.05).
      Collectively, these data indicate that PC has significant protective effects
      against damage induced by oxidative stress in mouse ovaries. The mechanisms of
      protection may be related to antioxidation and apoptosis reduction.

PMID- 25867395
TI  - Association between polymorphism of beta3-adrenoceptor gene and overactive
      bladder: a meta-analysis.
AB  - Genetic variations in the human beta3-adrenoceptor (beta3-AR) gene are known to
      be involved in insufficient relaxation of the bladder muscle during urine
      storage. The Trp64Arg polymorphism in the beta3-AR gene has been found to be an
      important regulator of the development of overactive bladder (OAB). However, the
      association between this polymorphism and OAB remains controversial. Therefore,
      we conducted a meta-analysis to explore the association between the Trp64Arg
      polymorphism and OAB risk. We examined 2 case-control studies, including a total
      of 149 OAB cases and 270 healthy controls. The meta-analysis results showed that
      the Arg allele of the beta3-AR gene is positively associated with OAB
      susceptibility, while Arg allele carriers (Trp64Arg + Arg64Arg) showed positive
      associations with OAB. These results also demonstrated that the Trp64Arg
      polymorphism in the beta3-AR gene is involved in the pathogenesis of OAB.

PMID- 25867396
TI  - Sexual genetic and simple sequence repeat (SSR) analysis for molecular marker
      development on the all hermaphrodite papaya.
AB  - The papaya (Carica papaya L.) is one of the most important economic tropical
      fruits in the world, and the hermaphrodite is the preferred type in field
      cultures. We analyzed the sexual ratio of offspring from the cultivar 'Taiwan
      Seed Station No. 7' (T7) by a self-cross and its cross with Taichung Sunrise
      (TS). Female progeny from the T7 self-crossing were not observed. This finding
      may be caused by a lethal gene that is linked to females. In this study, we
      selected 192 simple sequence repeats (SSRs) to analyze the polymorphism between
      T7 and TS. A total of 37 SSRs were identified for T7 and TS. In addition, 14 SSRs
      served as the molecular makers for identification of T7, TS and their hybrid
      offsprings. Thus, the results show that the genetic similarity between T7 and TS
      is rather high. This suggests that T7 may be a mutant of TS. Phylogenetic
      analysis from the SSR polymorphisms of the above parent strains and 15 F1
      offspring revealed the genetic distance of the F1 offspring located between T7
      and TS. The results of this study may provide an opportunity for elucidating the
      genetic characteristics of all hermaphrodites via identification of molecular
      makers. 

PMID- 25867397
TI  - Single nucleotide polymorphisms in the mitochondrial displacement loop and age-at
      onset of non-small cell lung cancer.
AB  - The associations between single nucleotide polymorphisms (SNPs) in the
      displacement loop (D-loop) of mitochondrial DNA (mtDNA) and cancer risk and
      disease outcome have been extensively analyzed. We investigated the association
      between age-at-onset and SNPs in the mitochondrial D-loop using a population
      based series of non-small cell lung cancer (NSCLC) patients. The D-loop region of
      mtDNA from NSCLC patients was amplified and sequenced. The age-at-onset curve of
      NSCLC patients was calculated using the Kaplan-Meier method at each SNP site and
      values were compared using the log-rank test. The SNP sites of nucleotides 200G/A
      and 16362T/C were identified to determine their association with age-at-onset of
      NSCLC using the log-rank test. The nucleotide 207G/A was identified for its
      association with age-at-onset at a borderline significance level (P = 0.060). We
      found that genetic polymorphisms in the D-loop were predictive markers for age-at
      onset in NSCLC patients. Accordingly, the analysis of genetic polymorphisms in
      the mitochondrial D-loop can be used to identify NSCLC patient subgroups at high
      risk of early onset. 

PMID- 25867398
TI  - Associations between genetic variants and the severity of metabolic syndrome in
      subjects with type 2 diabetes.
AB  - Metabolic syndrome (MetS) includes obesity, dyslipidemia, elevated blood
      pressure, and dysglycemia. Subjects with type 2 diabetes (T2D) exhibit features
      of MetS. The etiology of MetS is complex, involving both environmental and
      genetic factors. In this study, we examined the role of specific candidate
      genetic variants on the severity of MetS in T2D subjects. A total of 240 T2D
      subjects aged 35-64 years were recruited. Waist circumstance, plasma
      triglycerides, high-density lipoprotein cholesterol, fasting plasma glucose, and
      blood pressure were measured to define MetS. Subjects were divided into 4 groups
      according to MetS components. Target genes involved in fibrotic and inflammatory
      processes, insulin and diabetes, cell growth and proliferation, and hypertension
      were genotyped. A total of 13 genes and 103 single-nucleotide polymorphisms
      (SNPs) were analyzed to evaluate their genetic association with MetS severity in
      T2D subjects. Univariate ordinal logistic regression using a dominant model
      (homozygous for the major allele vs carriers of the minor allele) revealed 6 SNP
      markers within 4 genes with genotypes associated with MetS risk. For the SNP
      genotypes of rs362551 (SNAP25), rs3818569 (RXRG), rs1479355, rs1570070 (IGF2R),
      and rs916829 (ABCC8), heterozygotes showed a lower risk of MetS compared with the
      reference group. In addition, the CC genotype was comparable to the TT genotype
      for rs3777411. There was no gender-specific effect. In conclusion, our results
      suggest that among the Han Chinese population, several SNPs increase the risk of
      severe MetS in T2D subjects. Further study in a large population should be
      conducted.

PMID- 25867399
TI  - Influence of thoracic duct ligation on the lipid metabolism of patients with
      esophageal carcinoma after esophagectomy.
AB  - The aim of this study was to determine the influence of thoracic duct ligation on
      the lipid metabolism of patients with esophageal carcinoma after esophagectomy. A
      total of 74 patients with esophageal carcinoma who underwent esophagectomy were
      divided into 2 groups according to whether or not their thoracic duct was
      ligated. Thirty-nine patients were in the thoracic duct ligation group and the
      other 35 assigned to the control group. Enteral feeding was through a nasojejunal
      tube from the 1st day to the 8th day after operation, and liquid diet was
      provided starting on the 6th day. We compared the plasma concentrations of
      cholesterol (CHOL), triglycerides (TG), high-density lipoprotein (HDL), and low
      density lipoprotein (LDL) at different time points. There were no statistically
      significant differences between the two groups in CHOL, TG and HDL levels at
      different times. However, LDL levels in the thoracic duct ligation group were
      significantly lower at different times compared to the other group (P < 0.05),
      where they were the lowest at the end of the 1st month and then gradually
      recovered 3 months later. Thoracic duct ligation can effectively prevent
      chylomicrons from being transferred to the blood, reducing the generation of LDL.
      The establishment of collateral circulation was slow after the ligation of the
      thoracic duct, which had a negative effect on early postoperative nutrition of
      patients. 

PMID- 25867400
TI  - Induction function of siRNA-mediated survivin gene silencing on nasopharyngeal
      carcinoma cell apoptosis.
AB  - We examined the function of survivin gene expression in patients with
      nasopharyngeal carcinoma (NPC), as well as small interfering RNA (siRNA) on
      controlling CNE-2 NPC proliferation and apoptosis. Immunohistological methods, in
      situ hybridization, and reverse transcription-polymerase chain reaction technique
      were used to detect survivin protein and mRNA expression. We designed an siRNA
      sequence to inhibit survivin gene expression. The MTT method was used to examine
      the function of siRNA on controlling cell growth and proliferation. Induction of
      cell apoptosis by siRNA was examined by flow cytometry; electron microscopy was
      used to observe ultrastructure changes in CNE-2 cells. Western blotting was used
      to detect survivin gene expression. The survivin protein was expressed in 71.9%
      of cells, while its mRNA was expressed in 65.6% of cells. Relative mRNA
      expression was 4.16 x 10(-2); these data for the control groups were 23.3, 33.3,
      and 4.42 x 10(-4), respectively. Following transfection with 3 different siRNA
      sequences, survivin mRNA expression in CNE-2 cells was decreased. Inhibition of
      cell proliferation and rate of apoptosis increased with increasing siRNA
      concentration. Western blotting revealed decreased survivin expression and
      electron microscopy revealed ultrastructural changes in cancer cells. Survivin
      gene expression in NPC generally increased. In vitro transcription of siRNA
      decreased CNE-2 survivin gene expression, and different sequences of siRNA
      decrease gene expression in CNE-2 cells to varying degrees. Transfected siRNA3
      can effectively inhibit CNE-2 cell proliferation and induce apoptosis; gene
      silencing using siRNA may represent a new treatment for NPC.

PMID- 25867401
TI  - Polymorphisms of uric transporter proteins in the pathogenesis of gout in a
      Chinese Han population.
AB  - In this study, we analyzed single nucleotide polymorphisms (SNP) in urate
      transporter genes to examine the pathogenesis of gout. We conducted a 1:1-matched
      case-control study that included 110 patients with acute gout attacks as the
      patient group and 110 healthy age- and gender-matched subjects as the control
      group. Clinical parameters were recorded and blood biochemistry tests were
      conducted for both groups. Multivariate logistic regression analysis was used to
      analyze the data. Hyperuricemia, hypercholesterolemia, and hypertriglyceridemia
      were found to be the main risk factors for the onset of gout, with relative risks
      of 29.2 (P < 0.001), 25.5 (P = 0.003), and 11.2 (P < 0.001). For all detected
      SNP, rs2231142, located in ABCG2, showed the largest frequency differences for
      the G/G, G/T, and T/T genotypes between groups: the distribution of these
      genotypes in the case group was 22, 49, and 26 individuals, respectively, and was
      54, 38, and 9 individuals, respectively, in the control group. There was a
      statistically significant difference between the 2 groups (P < 0.001) and the
      odds ratio was 7.091 (95% confidence interval = 2.867-17.541). Other SNPs
      (rs1165196, rs1165205, rs1183201, rs17300741, rs2078267, rs2242206, rs3733591,
      and rs9358856) showed no significant difference between the groups (P > 0.05).
      The risk factors of gout were hyperuricemia, hypercholesterolemia,
      hypertriglyceridemia, and the T/T genotype of the rs2231142 locus in the ABCG2
      gene; expression of the G/G genotype may be a protective factor against gout
      development.

PMID- 25867402
TI  - Impact and significance of EGCG on Smad, ERK, and beta-catenin pathways in
      transdifferentiation of renal tubular epithelial cells.
AB  - We investigated the impact and signal transduction mechanisms of epigallocatechin
      3-gallate (EGCG) on transdiffer-entiation of renal tubular epithelial cells. Rat
      renal tubular epithelial cells (NRK-52E) were randomly divided into a normal
      control group, transforming growth factor (TGF)-b1-induced group (10 ng/mL), and
      intervention groups with 200 mg/L EGCG + 10 ng/mL TGF-b1 and 400 mg/L EGCG + 10
      ng/mL TGF-b1. Tested cells were collected after 48 h. Levels of a-smooth muscle
      actin (alpha-SMA) and cytokeratin-18 were detected using immunohistochemical
      methods. Western blotting was used to detect cytoplasmic Pi-extracellular
      receptor kinase 1/2 (ERK1/2), Pi-Smad3 protein, and nuclear b-catenin protein.
      mRNA expression of ERK2, Smad3, and beta-catenin was measured by reverse
      transcription-polymerase chain reaction. After induction by TGF-b1, cytokeratin
      18 expression in the renal tubular epithelial cells decreased and a-SMA
      expression appeared. mRNA expression of cytoplasmic Pi-Smad3 and Pi-ERK1/2,
      Smad3, ERK2, and b-catenin protein expression increased, while beta-catenin mRNA
      decreased. These changes were reduced after intervention by EGCG. EGCG may be
      helpful for maintaining the renal tubular epithelial cell phenotype and reducing
      the degree of TGF-b1- induced cell transdifferentiation, which may be related to
      the signal transduction pathway of ERK, Smad3, and beta-catenin.

PMID- 25867403
TI  - Effect of casein genes - beta-LGB, DGAT1, GH, and LHR - on milk production and
      milk composition traits in crossbred Holsteins.
AB  - The objectives of this study were to determine the effects of a single gene and
      composite genotype of the casein gene family, including the beta-lactoglobulin
      gene (beta-LGB), acyl-CoA: diacylglycerol acyltransferase 1 gene (DGAT1), growth
      hormone gene (GH), and luteinizing hormone receptor gene (LHR) on milk yield,
      milk composition, the percentage of fat, protein, solids-not-fat, and total solid
      in crossbred Holsteins. A total of 231 crossbred Holstein cows were examined for
      the study. The genotype of the beta-casein gene was analyzed by allele-specific
      polymerase chain reaction, while the alpha-S1, alpha-S2, kappa-casein, DGAT1,
      beta-LGB, and GH genes were analyzed using a polymerase chain reaction
      restriction fragment length polymorphism assay. The association between genes and
      milk yield and milk composition was analyzed. Three pairs of genes, for which
      significant associations were detected, were beta + kappa-casein, DGAT1 + beta
      casein, and GH + beta-LGB. In the single-gene model, most loci are significantly
      associated with traits. A significant association between the composite genotype
      and the traits was detected in all composite genotypes. GH + beta-LGB appears to
      be the most suitable variants for improving milk production and percentage of
      milk protein. Overall, the effects of the composite genotype and single gene were
      different. A physical or functional relationship between genes is necessary for
      investigating gene markers.

PMID- 25867404
TI  - Protective effects of ascorbic acid and vitamin E on antioxidant enzyme activity
      of freeze-thawed semen of Qinchuan bulls.
AB  - The aim of this study was to determine the protective effects of the combination
      of ascorbic acid (Vc) and vitamin E (VE) on antioxidant enzyme activity, sperm
      motility, viability, and acrosome integrity of Qinchuan bulls after freeze-thaw.
      In this study, we determined the effects of Vc and VE on the activity of the
      antioxidant enzyme defense system comprising glutathione peroxidase (GSH-Px),
      glutathione reductase (GR), catalase (CAT), and superoxide dismutase (SOD). The
      combination of Vc and VE had protective effects on sperm motility and viability.
      With respect to acrosome integrity and the activity of GR and SOD, differences
      were observed between the experimental groups with added Vc (7 mg/mL) and VE
      (0.12 IU/mL) and the control group. The activity of GSH-Px in the experimental
      group (1400 IU/mL Vc and 0.12 IU/mL VE) was not different (P > 0.05) compared
      with that in the control group, while the activity of CAT showed a significant
      difference between the 2 groups (P < 0.05). Therefore, we inferred that the
      combination of Vc (1400 IU/mL) and VE (0.12 IU/mL) protected the sperm quality in
      the freeze-thaw process. 

PMID- 25867405
TI  - Effect of a pre-microRNA-149 (miR-149) genetic variation on the risk of ischemic
      stroke in a Chinese Han population.
AB  - Clinical and experimental data have demonstrated that genetic factors play an
      important role in determining the susceptibility to ischemic stroke (IS). The
      present study was performed to clarify the association between the pre-microRNA
      149 (miR-149) single nucleotide polymorphism rs71428439 and the risk of IS in the
      Jiangsu Han population. Polymerase chain reaction and restriction fragment length
      polymorphism were performed to identify the genotypes of the miR-149 single
      nucleotide polymorphism rs71428439 in 730 unrelated subjects (IS, 348; healthy
      controls, 382). Plasma levels of homocysteine were determined using a radioassay
      kit. Compared to healthy controls, IS patients had a lower frequency of GG
      genotype distribution of the hsa-mir-149 polymorphism (11.5 vs 16.0%) and a
      higher frequency of TT (46.6 vs 39.0%). The risk of IS was significantly lower
      among subjects carrying the GG genotype than subjects carrying the AA genotype
      (odds ratio (95% confidence interval): 0.603 (0.382- 0.952), P = 0.030) or at
      least carrying the G allele than patients carrying the A allele (odds ratio (95%
      confidence interval): 0.769 (0.620-0.954), P = 0.019). Levels of folate were
      statistically higher in patients with the TT genotype (8.59 +/- 7.75 ng/mL) than
      in those with the CC genotype (6.32 +/- 5.97 ng/mL) in IS patients. Our results
      suggest that the miR- 149 single nucleotide polymorphism rs71428439 influences
      plasma levels of homocysteine and is associated with IS risk in the Jiangsu Han
      population.

PMID- 25867406
TI  - Evaluation of the genetic diversity of Bupleurum using amplified fragment length
      polymorphism analysis.
AB  - Radix bupleuri (Chaihu), the dried root of the Bupleurum plant, is an important
      component of traditional Chinese medicine. In this study, we examined the genetic
      diversity of 11 Bupleurum strains, originating from 7 provinces in China, using
      amplified fragment length polymorphism analysis. A total of 274 polymorphic bands
      were obtained using 6 primer combinations, indicating a high level of
      polymorphism across all strains. An estimation of the relative relationships
      among strains revealed genetic distances ranging from 0.2183 to 0.7372, with an
      average of 0.4161. The 2 most closely related varieties were Bupleurum chinense
      DC. strains collected from Lushi, Henan, and Zhangjiakou, Hebei, with a genetic
      nearness of 0.2183. Hierarchical clustering divided the strains into 3 main
      groups, with B. falcatum L. from Hebei and Liaoning Provinces forming a cluster
      that diverged from that of B. smithii Wolff. and B. chinense DC. B. falcatum L.
      (Sandao chaihu), collected from Heze, Shandong, clustered independently of the
      other strains, suggesting that this strain may have been introduced from a
      different location or that it arose as a result of intraspecific variation. B.
      smithii Wolff. (Hei chaihu) was closely associated with B. scorzonerifolium
      Willd. (Nan chaihu) and B. chinense DC. (Bei chaihu), suggesting a common genetic
      origin.

PMID- 25867407
TI  - Microsatellite analysis of genetic diversity and genetic structure in five
      consecutive breeding generations of mandarin fish Siniperca chuatsi (Basilewsky).
AB  - In this report, 10 polymorphic microsatellites were applied to assess the genetic
      diversity and genetic differentiation of 5 consecutive breeding generations of
      mandarin fish, Siniperca chuatsi (Basilewsky). The results from total number of
      alleles, average polymorphism information content, and average homozygosity and
      heterozygosity showed that the genetic diversity of the breeding population was
      decreasing. The genetic identity between F1 and its descendant generations (F2,
      F3, F4, F5) decreased (from 0.9248 to 0.8803), while the genetic distance (from
      0.0782 to 0.1275) and fixation index (from 0.03796 to 0.07393) increased. The
      allele frequency of SS181-235 and SS211-246 changed regularly in the 5 breeding
      generations, and they may be negatively associated with the selected trait, which
      needs to be confirmed by further research. Our study indicated that selective
      breeding was an efficient strategy for mandarin fish. In the process of breeding,
      some deleterious genes were phased out, and the genetic structure of the breeding
      populations became stable. 

PMID- 25867408
TI  - Analysis of carcass and meat quality traits and nutritional values of hybrid wild
      boars under different crossing systems.
AB  - The aim of this study was to analyze the results of two crossing systems between
      wild boars and different domesticated pig breeds. Hybrid wild boars were produced
      by crossing captured wild boars with Meishan pigs and LY sows according to the
      traditional production system. The resultant commercial hybrids were black and
      white in coat color, respectively. Significant differences were found in the
      carcass and meat quality traits and nutritional values between these two hybrid
      wild boars. Compared with the white hybrid wild boars, at the age of 300 days,
      the body weight of black hybrid wild boars was 9.41 kg lower, while percent lean
      was 2.51% less and percent fat 2.45% higher (P < 0.05). The black hybrid wild
      boars had higher pH2 (6.17 vs 6.09) and intramuscular fat (3.34 vs 2.52%), lower
      drip loss (2.21 vs 2.68%) and shear force (44.00 vs 52.23) (P < 0.05), and more
      unsaturated fatty acids and essential amino acids (P < 0.05). In conclusion,
      cross breeding was shown to be an effective method to improve the overall
      production performance of wild boars, but crossing with different dam line breeds
      caused different responses. Compared with the white hybrid wild boars, the black
      hybrid wild boars had worse growth rate and carcass traits, but better meat
      quality traits and nutritional values. 

PMID- 25867409
TI  - Association between single-nucleotide polymorphisms of fatty acid synthase gene
      and meat quality traits in Datong Yak (Bos grunniens).
AB  - Fatty acid synthase (FASN) is a key enzyme in fatty acid anabolism that plays an
      important role in the fat deposit of eukaryotic cells. Therefore, in this study,
      we detected 2 novel single-nucleotide polymorphisms (SNPs) in the FASN gene in
      313 adult individuals of Datong yak using polymerase chain reaction-single strand
      conformation polymorphism and DNA sequencing techniques. SNP g.5477C>T is located
      in intron 3 of FASN, and 3 genotypes, HH, HG, and GG, were detected in this
      mutation site. SNP g.16930T>A is located in exon 37 of FASN, and 2 genotypes, EE
      and EF, were detected in this site. Association analysis of these 2 SNPs with
      meat quality traits showed that in SNP g.5477C>T, yaks with the HH genotype and
      HG genotype had significantly higher intramuscular fat content than individuals
      with the GG genotype (P < 0.01). In SNP g.16930T>A, yaks with the EE genotype
      also had significantly higher IMF content than individuals with the EF genotype
      (P < 0.01). The results indicate that FASN may be used as a candidate gene
      affecting intramuscular fat content in Datong yaks.

PMID- 25867410
TI  - Dynamical evaluation of vaginal micro-ecosystem in a Chinese woman with recurrent
      vulvovaginal candidiasis.
AB  - We reported a rare case of recurrent vulvovaginal candidiasis (RVVC) in this
      study. Through dynamic evaluation of the vaginal micro-ecosystem, we found that
      only depuratory degree, spores, blastospores, and hyphae were specific indicators
      and the "barometer" of RVVC development. Therefore, an understanding of vaginal
      micro-ecological changes can help clinicians to improve the treatment of patients
      with RVVC.

PMID- 25867411
TI  - Role of IL-6 polymorphism on the development of cardiovascular events and
      coronary artery disease in patients receiving hemodialysis.
AB  - We aimed to investigate the role of IL-6 polymorphism on the development of
      cardiovascular events and coronary artery disease in patients receiving
      hemodialysis. Blood samples were collected from 216 patients receiving
      hemodialysis treatment. Polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) was used to genotype IL-6 -634C/G, -174G/C and -572C/G.
      By multivariate analysis, we found that the IL-6 -634GG genotype was associated
      with increased risk of cardiovascular events in patients receiving hemodialysis,
      with HR (95%CI) of 4.07 (1.20-15.70). Similarly, we found that the IL-6-174CC
      genotype was related to the onset and development of cardiovascular events in
      patients receiving hemodialysis, with HR (95%CI) of 3.33 (1.21-9.51). However, we
      did not find an association between IL-6 -572C/G polymorphism and risk of
      cardiovascular events in patients receiving hemodialysis.

PMID- 25867412
TI  - Loss of STAG2 causes aneuploidy in normal human bladder cells.
AB  - The aim of this study was to determine how the function of human stromal antigen
      2 (STAG2) plays an important role in proper chromosome separation. STAG2 mRNA in
      normal bladder cells and bladder tumor cells was evaluated by RT-PCR. The protein
      levels of STAG2 in normal bladder cells and bladder tumor cells were determined
      by western blot. A cell proliferation assay was used to measure the growth of
      tumor cells and STAG2-inhibited normal cells, and STAG2- inhibited normal cells
      were subjected to karyotype analysis. Both STAG-2 mRNA and protein expression
      levels were lower in bladder cancer cells compared to the controls. Knockdown of
      STAG2 caused aneuploidy in normal bladder cells, leading to a decreased
      expression of the cohesin complex components SMC1, SMC3 and RAD21, but there was
      no obvious effect of STAG2 knockdown on cell proliferation. Our study indicated
      that abnormal expression of STAG2 could cause aneuploidy in normal bladder cells.

PMID- 25867413
TI  - Risk factors for damaged liver function after chemotherapy in hepatitis B virus
      carriers with non-Hodgkin lymphoma.
AB  - The goal of this study was to investigate damaged liver function after
      chemotherapy in hepatitis B virus (HBV) carriers with non-Hodgkin lymphoma (NHL)
      and to evaluate risk factors associated with a high risk of damaged liver
      function. Clinical histories of 134 HBV carriers with NHL who were treated with
      chemotherapy were obtained and analyzed for the occurrence of damaged liver
      function and other related high-risk factors. Analysis showed that 76 patients
      (56.7%) had damaged liver function after chemotherapy: 6 patients (7.9%) had I
      degree, 17 patients (22.4%) had II degree, 20 patients (26.3%) had III degree,
      and 33 patients (43.4%) had IV degree damage. After treatment, 18 patients
      (23.7%) continued to receive chemotherapy according to their original schedule,
      39 patients (51.3%) delayed chemotherapy, 16 patients (21.1%) stopped
      chemotherapy, and 3 patients (3.9%) died. Analysis of a binary multivariate
      logistic regression model showed that administration of steroids was a high-risk
      factor for damaged liver function after chemotherapy in NHL patients. The
      incidence of damaged liver function after chemotherapy is high among HBV carriers
      with NHL; therefore, administration of steroid chemotherapy is a high-risk
      factor. 

PMID- 25867414
TI  - Molecular cloning and expression profile of an ATP-binding cassette (ABC)
      transporter gene from the hemipteran insect Nilaparvata lugens.
AB  - The ATP-binding cassette (ABC) transporters belong to a large superfamily of
      proteins that have important physiological functions in all living organisms. In
      insects, ABC transporters have important functions in the transport of molecules,
      and are also involved in insecticide resistance, metabolism, and development. In
      this study, the Nilaparvata lugens Stal (Hemiptera: Delphacidae) ABCG (NlABCG)
      gene was identified and characterized. The complete mRNA sequence of NlABCG was
      2608-bp long, with an open reading frame of 2064 bp encoding a protein comprised
      of 687 amino acids. The conserved regions include three N-glycosylation and 34
      phosphorylation sites, as well as seven transmembrane domains. The amino acid
      identity with the closely related species Acyrthosiphon pisum was 42.8%.
      Developmental expression analysis using quantitative real-time reverse
      transcriptase PCR suggested that the NlABCG transcript was expressed at all
      developmental stages of N. lugens. The lowest expression of NlABCG was in the 1st
      instar, and levels increased with larval growth. The transcript profiles of
      NlABCG were analyzed in various tissues from a 5th instar nymph, and the highest
      expression was observed in the midgut. These results suggest that the sequence,
      characteristics, and expression of NlABCG are highly conserved, and basic
      information is provided for its functional analysis.

PMID- 25867415
TI  - Administration of low-dose cyclosporine alone for the treatment of elderly
      patients with membranous nephropathy.
AB  - This study aimed to investigate the effects of administration of low-dose
      cyclosporine A (CsA) alone and the combination of low-dose CsA and a low-dose
      hormone for the treatment of elderly patients with membranous nephropathy. We
      divided 27 patients into two groups as follows: low-dose CsA group (group A) and
      the group receiving a combination of a low-dose hormone and low-dose CsA (group
      B). The treatment and follow-up times were >= 6 months. We observed no difference
      in gender, age, serum creatinine levels, estimated glomerular filtration rate
      (eGFR), and 24-h urinary protein levels between the two groups before treatment;
      in addition, the rates of complete and partial remission were not different 6
      months after treatment. The rate of complications in group B was higher than that
      in group A (84.6 vs 35.7%, respectively; t = 0.018). While the pretreatment eGFR
      of patients who achieved remission was significantly higher than that of patients
      who did not achieve remission, the 24-h urinary protein levels and incidence of
      hypertension were significantly lower than those of patients who did not achieve
      remission (t = 0.042, 0.035 and 0.043, respectively). The efficacy of
      administration of low-dose CsA alone and in combination with a low-dose hormone
      was similar; the efficacy was related to eGFR, urinary protein levels, and the
      incidence of hypertension before the treatment. The side effects of
      administration of CsA alone were significantly lower than those of the
      combination treatment.

PMID- 25867416
TI  - Expression of genes related to tolerance to low temperature for maize seed
      germination.
AB  - The aim of this study was to characterize maize lines tolerant to cold
      temperatures during the germination process. Seeds from lines with different
      levels of tolerance to low temperatures were used; 3 lines were classified as
      tolerant and 3 as susceptible to low germination temperatures. A field was set up
      to multiply seeds from selected lines. After the seeds were harvested and
      classified, we conducted physiological tests and analyzed fatty acid content of
      palmitic, stearic, oleic, linoleic, linolenic, and eicosenoic acids. In proteomic
      analysis, the expression of heat-resistant proteins, including catalase,
      peroxidase, esterase, superoxide dismutase, and alpha-amylase, were evaluated.
      Transcript analysis was used to measure the expression of the genes AOX1, AOX2,
      ZmMPK-17, and ZmAN-13. The material showing the highest susceptibility to low
      germination temperatures contained high saturated fatty acid content. Expression
      of alpha-amylase in seeds soaked for 72 h at a temperature of 10 degrees C was
      lower than expression of alpha-amylase when soaked at 25 degrees C for the same
      amount of time. We observed variation in the expression of heat-resistant
      proteins in seeds of the lines evaluated. The genes AOX and Zm-AN13 were
      promising for use in identifying maize materials that are tolerant to low
      germination temperatures. 

PMID- 25867417
TI  - Molecular characterization, expression, and functional analysis of NOD1 in
      Qingyuan partridge chicken.
AB  - Nucleotide-binding oligomerization domain-containing protein-1 (NOD1) is a
      cytoplasmic pattern recognition receptor (PRR) and a key member of the NOD-like
      receptor (NLR) family. It has been reported that NLRs recognize a variety of
      microbial infections to induce the host innate immune response via modulation of
      NF-kappaB signaling. However, no reports on chicken NOD1 have been reported to
      date. In the current study, the full-length cDNA sequence of NOD1 was cloned. The
      complete open reading frame of NOD1 contains 2856 bp and encodes a 951 amino acid
      protein. Structurally, it is comprised of one caspase recruitment domain at the N
      terminus, seven leucine-rich repeat regions at the C-terminus, and one NACHT
      domain between the N and C-termini. Phylogenetic analyses showed that chicken
      NOD1 clusters with duck and turkey. Furthermore, tissue-specific expression
      analyses of chicken NOD1 were performed using quantitative reverse transcription
      PCR. NOD1 is widely distributed in various tissues, with the highest expression
      observed in testes. Finally, induced expression of chNOD1 and its associated
      adaptor molecule receptor-interacting protein 2, as well as the effector molecule
      NF-kappaB, was observed following S. enterica serovar Enteritidis infection.
      These findings highlight the important role of chicken NOD1 in response to
      pathogenic invasion. The present study is the first report of the cloning,
      expression, and functional analysis of chicken NOD1 and provides the foundation
      for future research on the structure and function of chicken NOD1.

PMID- 25867418
TI  - Overwhelming postsplenectomy infection.
AB  - This report aims to deepen the understanding of the pathogenesis, diagnosis,
      clinical characteristics, and treatment of overwhelming postsplenectomy infection
      (OPSI). A patient treated at Taihe Hospital for tuberculous OPSI is described,
      and relevant literature is reviewed. Broad-spectrum antibiotics, suppression of
      the systemic inflammatory reaction, and anti-shock measures were the keys to the
      successful treatment of this condition. OPSI is a life-threatening condition and
      has a high mortality rate. Early diagnosis, use of anti-inflammatory
      glucocorticoids, and administration of high-dose gamma globulin and ulinastatin
      for the treatment of OPSI may improve outcomes. 

PMID- 25867419
TI  - Inactivation of Rab23 inhibits the invasion and motility of pancreatic duct
      adenocarcinoma.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is charac-terized by a poor prognosis and
      high mortality rate. In this study, we investigated the expression of Rab23 in
      non-tumor pancreatic tissues and PDACs via immunohistochemistry. Rab23 was found
      in 39 of 58 (67.2%) and in 11 of 30 (36.7%) of the PDAC and non-tumor pan-creatic
      tissue samples (P = 0.0073), respectively. There were signifi-cant correlations
      between Rab23 expression and unfavorable variables, including cancer
      differentiation level (P = 0.0089), lymph nodal (P = 0.0099), and distant
      metastases (P = 0.0173). Inactivation with small interfering RNA against Rab23 in
      the human pancreatic cancer cell line Panc-1 inhibited the migration and invasive
      potential of the cells. Our data provide new insight into the essential role of
      Rab23 in PDAC inva-sion and metastasis and suggest that Rab23 expression is a
      useful indi-cator of metastatic potential; hence, it may be a new therapeutic
      target for this common malignancy.

PMID- 25867420
TI  - Rifampicin resistance among multi-resistant MRSA clinical isolates from Chennai,
      India, and their molecular characterization.
AB  - High-level methicillin-resistant Staphylococcus aureus (MRSA) isolates show rapid
      evolution of rifampicin resistance, forcing reliance upon expensive and often
      inferior antibiotics to manage these infections. Accordingly, this study was
      conducted to: 1) evaluate the level of multidrug resistance among hospital
      associated MRSA isolates from Chennai, India; 2) determine their rifampicin
      resistance and molecular characterization; and 3) analyze the identified rpoB
      gene mutations for predominant high-level rifampicin resistance-associated
      nucleotide changes. Conventional laboratory techniques and antibiogram evaluation
      by disc diffusion were utilized for isolate phenotypic identification. Among the
      54 isolates obtained, 74% (42) were found to be MRSA. All the isolates exhibited
      complete susceptibility to linezolid and vancomycin, and variable resistance to
      conventional antibiotics; the MAR index value calculated was 0.64. Genotypic
      identification of the high-level rifampicin-resistant isolate S. aureus KM05 was
      established through rpoB amplification and sequencing. The evolutionary
      relationship of KM05 to other isolates and its rpoB gene mutation status was
      determined to understand the genetic basis of its high rifampicin resistance. The
      S. aureus KM05 rpoB gene yielded >= 98% sequence similarity and a close
      phylogenetic relationship with other known reference database organisms. It also
      showed mutational changes in three rpoB codon positions encoding amino acids at
      positions 455, 481, and 529. These results have established the prevalence of
      rifampicin resistance among Chennai hospital MRSA isolates, and suggest that the
      predominant high-level resistance nucleotide changes would serve to form a basis
      for their diagnosis and control of rifampicin-resistant MRSA.

PMID- 25867421
TI  - Cloning of an anthocyanidin synthase gene homolog from blackcurrant (Ribes nigrum
      L.) and its expression at different fruit stages.
AB  - Anthocyanidin synthase (ANS), a 2-oxoglutarate (2OG) and Fe(II)-dependent
      oxygenase, catalyzes the penultimate step in anthocyanin biosynthesis, from
      leucoanthocyanidins to anthocyanidins, the first colored compound in the
      anthocyanin pathway. In this study, a full-length, 1427-bp long cDNA named
      RnANS1, which is homologous to the anthocyanidin synthase gene, was cloned from
      blackcurrant using a homologous cloning strategy. RnANS1 is highly homologous to
      other plant ANS genes at both the nucleotide and amino acid sequence levels. The
      deduced protein contains domains conserved in the 2OG and Fe(II)-dependent
      oxygenase, and is phylogenetically closely related to Paeonia suffruticosa and
      Paeonia lactiflora. The expression of RnANS1 was upregulated during fruit
      maturation, and correlated with the accumulation of anthocyanins and soluble
      carbohydrates in the fruit. Further characterization of the structure and
      expression patterns of RnANS1 will clarify our understanding of anthocyanin
      biosynthesis in blackcurrant, and support the development of molecular approaches
      to manipulate anthocyanin production in this plant.

PMID- 25867422
TI  - Safety of recombinant human granulocyte-macrophage colony-stimulating factor in
      healing pediatric severe burns.
AB  - We explored the safety of recombinant human granulocyte-macrophage colony
      stimulating factor (rhGM-CSF) for healing burns in children. Subjects were
      randomly assigned to two groups: the experimental group received external rhGM
      CSF gel, and the control group received rhGM-CSF gel matrix components, applied
      to the burn surface. Neither group was given any other drugs that promote wound
      healing. Each day we recorded the pulse, body temperature, and respiration status
      in the two groups. We detected the blood routine, urine routine, and hepatic and
      renal function before the patients received drug treatment and after 72 h. The
      wound scab and healing states in the two groups were recorded every 4 days to
      evaluate wound healing rate and time taken for complete healing. Adverse
      reactions and their rate of occurrence were also recorded. The median time of
      healing was 15 days in the experimental group and 19 days in the control group
      (log-rank chi(2) = 5.139, P < 0.05). After 10 days, the experimental group
      healing rate was consistently higher than that of the control group
      (significantly different using intuitive analysis), suggesting the experimental
      group method was more effective. There were no obvious adverse reactions. There
      was no significant difference between the blood routine, urine routine, and liver
      and kidney function in the two groups before the treatment and after 3 days (P >
      0.05). Compared with saline treatment of severe burns, rhGM-CSF can effectively
      shorten the healing time without significant adverse reactions, and is an
      effective and safe treatment for burns in children. 

PMID- 25867423
TI  - Overexpression of the A-FABP gene facilitates intermuscular fat deposition in
      transgenic mice.
AB  - Adipocyte fatty acid-binding protein (A-FABP), the most abundant FABP in
      adipocytes, controls fatty acid uptake, transport, and metabolism in fat cells.
      We constructed a transgenic mice model that overexpressed the cattle A-FABP gene
      to investigate the relationship between A-FABP expression and intermuscular fat
      deposition. There was no significant difference in body weight and serum
      biochemical indexes between transgenic and wild-type mice. Further, there were no
      significant differences in intermuscular triglyceride content and A-FABP
      expression levels over three generations of transgenic mice. However, abdominal
      adipose rate, A-FABP protein content, and intermuscular triglyceride levels of
      transgenic mice were significantly higher than those of wild-type mice. In
      addition, triglycerides were remarkably higher in the skeletal muscle but lower
      in the myocardium of transgenic mice. Thus, overexpression of cattle A-FABP gene
      promoted fat deposition in the skeletal muscle of transgenic mice. 

PMID- 25867424
TI  - A promoter trap vector for knocking out bovine myostatin gene with high targeting
      efficiency.
AB  - With the development of gene targeting approaches, genomic mutation technologies
      in livestock animals such as gene trapping, zinc finger nucleases (ZFNs),
      transcription activator-like effector nucleases, and clustered regularly
      interspaced short palindromic repeats and their associated systems have been
      improved. Although ZFNs have been used for gene targeting in many species, the
      off-target sites are still present. Using gene trapping, the workload of
      screening of targeted clones was decreased by generating a smaller number of drug
      resistant clones. Determining whether the efficiency of gene trapping is lower
      than that of ZFNs for a specific gene has been challenging. In this study, to
      knock out the bovine myostatin gene, we constructed a promoter trap vector and
      compared its efficiency with that of ZFNs. The promoter trap vector contained a
      green fluorescent protein sequence without the promoter and a neomycin
      phosphotransferase (neo(R)) cassette driven by the phosphoglycerate kinase
      promoter. When the trapping vector was inserted downstream of the endogenous
      promoter, the fluorescent protein gene was expressed. The targeted-positive cell
      clones were identified based on green fluorescence and G418 double selection,
      followed by polymerase chain reaction analysis and sequencing. The targeting
      efficiency reached 5%. Compared with the efficiency of ZFN pairs (5.17 and
      2.86%), the promoter trap vector PIII-myostatin could knock out the bovine
      myostatin gene. Therefore, gene trapping may be an effective tool for genomic
      modification. 

PMID- 25867425
TI  - Identification of molecular markers associated with fruit traits in olive and
      assessment of olive core collection with AFLP markers and fruit traits.
AB  - The purpose of this study was to characterize olive core collection with
      amplified fragment length polymorphism (AFLP) markers and fruit traits and to
      determine AFLP markers significantly associated with these fruit characters in
      olive. A total of 168 polymorphic AFLP markers generated by five primer
      combinations and nine fruit traits were used to characterize relationships
      between 18 olive cultivars. Although all olive cultivars were discriminated from
      each other by either AFLP markers (<0.75 similarity level) or fruit traits,
      clustering based on the AFLP markers and fruit traits was not significantly
      correlated (r = 0.13). Partial clustering of olive cultivars by AFLP markers
      according to their geographical origin was observed. Associations of AFLP markers
      with fruits were determined using a multiple-regression analysis with stepwise
      addition of AFLP markers. Significant associations between eight AFLP markers and
      fruit traits were identified. While five AFLP markers demonstrated significant
      negative correlation with fruit and stone weight, width and length and total
      polyphenols (P < 0.05), three AFLP markers displayed significant positive
      correlation with alpha-tocopherol and gamma-tocopherol (P < 0.01). This is the
      first report on the association of molecular markers with fruit traits in olive.
      Molecular markers associated with morphological and agronomic traits could be
      utilized for the breeding of olive cultivars. However, the association power of
      these markers needs to be confirmed in larger populations, and highly correlated
      markers should then be converted to PCR-based DNA markers such as sequence
      characterized amplified region markers for better utilization. 

PMID- 25867426
TI  - Involvement of the mitfa gene in the development of pigment cell in Japanese
      ornamental (Koi) carp (Cyprinus carpio L.).
AB  - A colored phenotype is an important feature of ornamental fish. In mammals,
      microphthalmia-associated transcription factor (MITF) was found to regulate the
      development of melanocytes. In this study, the mitfa cDNA was first cloned from
      the Japanese ornamental (Koi) carp (Cyprinus carpio L.), an important ornamental
      freshwater fish. The full-length cDNA of the mitfa gene contains 1634 bp, coding
      for 412 amino acids in Koi. The identity degree of mitfa amino acid sequences
      between the Koi carp and zebrafish is 92.9%. We tested the expression of the
      mitfa gene in several varieties of Koi using reverse transcription-polymerase
      chain reaction and found that the mitfa gene is highly expressed in the skin
      tissues of the Taisho sanke and the Procypris merus. Interestingly, the mitfa
      gene was also expressed in the Kohaku and Yamabaki ogon, although melanocytes
      were not observed in the skin. Koi carp embryos were transparent and colorless,
      while after hatching, different types of pigment cells successively emerged in a
      fixed order. In Taisho sanke, melanocytes first appeared in the trunk at
      approximately 12 days of age. Subsequently, there was a large area of melanocytes
      by 30 days of age. The expression level of the mitfa mRNA was low in early
      embryos and newly hatched larvae, and increased to high levels in 30-day-old fry.
      The results show that the mitfa gene is involved in regulating fish body color in
      the development of both melanocytes and pigment cells.

PMID- 25867427
TI  - Identification of conserved microRNAs and their target genes in Nile tilapia
      (Oreochromis niloticus) by bioinformatic analysis.
AB  - MicroRNAs (miRNAs) are a class of non-coding RNAs that play important roles in
      posttranscriptional regulation of target genes. miRNAs are involved in multiple
      biological processes by degrading targeted mRNAs or repressing mRNA translation
      in various organisms. Their conserved nature in various organisms makes them a
      good source of new miRNA discovery using comparative genomic approaches. In the
      present study, conserved Nile tilapia (Oreochromis niloticus) miRNAs were
      identified using a bioinformatic strategy based on expressed sequence tag and
      genome survey sequence databases. A total of 21 new miRNAs were detected and were
      found to belong to 17 families. Using mature miRNA sequences as queries,
      potential targets for tilapia miRNAs were predicted using a local BLAST program
      and the miRanda software. Target proteins identified using miRanda and BLAST
      analyses included transcription factors and molecules important in metabolism,
      transportation, immunity, stress-related activity, growth, and development. These
      miRNAs and their targets in tilapia may increase the understanding of the role of
      miRNAs in regulating the growth and development of tilapia. 

PMID- 25867428
TI  - Molecular identification of phosphate-solubilizing native bacteria isolated from
      the rhizosphere of Prosopis glandulosa in Mexicali valley.
AB  - One of the main limitations in intensive crop production in Northwestern Mexico
      is the dependence on the use of phosphate fertilizer. In this study, we isolated
      indigenous microorganisms with phosphate solubilization capacities from mesquite
      (Prosopis glandulosa) present in the Mexicali valley. In total, 4 bacteria were
      isolated from the rhizosphere of mesquite, including ICA01, ICA02Ba, ICA03Bs, and
      ICA04Ma. The bacterial isolates were identified based on their phenotypic and 16S
      rRNA gene sequencing data to be Acinetobacter calcoaceticus. The results showed
      that ICA01 was the most efficient in solubilizing phosphate, followed by ICA02Ba
      and ICA03Bs, while ICA04Ma showed the lowest phosphate-solubilizing activity. The
      pH value of the culture medium decreased with bacterial growth, suggesting that
      these strains produce organic acids that solubilize phosphorus. These results
      will be useful for biotechnological studies and A. calcoaceticus may be employed
      for biofertilization programs in northwest Mexico.

PMID- 25867429
TI  - Cloning and sequence analysis of sucrose phosphate synthase gene from varieties
      of Pennisetum species.
AB  - Sucrose phosphate synthase (SPS) is an enzyme used by higher plants for sucrose
      synthesis. In this study, three primer sets were designed on the basis of known
      SPS sequences from maize (GenBank: NM_001112224.1) and sugarcane (GenBank:
      JN584485.1), and five novel SPS genes were identified by RT-PCR from the genomes
      of Pennisetum spp (the hybrid P. americanum x P. purpureum, P. purpureum Schum.,
      P. purpureum Schum. cv. Red, P. purpureum Schum. cv. Taiwan, and P. purpureum
      Schum. cv. Mott). The cloned sequences showed 99.9% identity and 80-88%
      similarity to the SPS sequences of other plants. The SPS gene of hybrid
      Pennisetum had one nucleotide and four amino acid polymorphisms compared to the
      other four germplasms, and cluster analysis was performed to assess genetic
      diversity in this species. Additional characterization of the SPS gene product
      can potentially allow Pennisetum to be exploited as a biofuel source.

PMID- 25867430
TI  - Reproductive outcome of a case with familial balanced translocation t(3;6):
      implications for genetic counseling.
AB  - Although it is known that parental carriers of structural chromosomal
      rearrangements are associated with recurrent pregnancy loss, subsequent natural
      pregnancies remain possible. We examined the reproductive outcome of a familial
      balanced translocation with t(3;6)(q12;q27). Karyotyping of the proband revealed
      46,XY chromosomes with the balanced translocation t(3;6). The first 2 pregnancies
      resulted in spontaneous abortions. Based on the proband karyotype, his father and
      half-brother were subjected to cytogenetic analysis, and both showed 46,XY,
      t(3;6)(q12;q27). After genetic counseling, the proband chose to continue the
      pregnancy. During the third pregnancy, the subject gave birth to a normal male
      infant. For parental carriers with balanced chromosomal translocations, natural
      pregnancy should be considered during genetic counseling. 

PMID- 25867431
TI  - Molecular characterization, expression patterns, and promoter activity analysis
      of PGM1 in pigs.
AB  - The phosphoglucomutase 1 (PGM1) gene was differentially expressed in tissues of
      Chinese Meishan and Large White pigs. In this study, the promoter region,
      expression profile, and genetic mutations of the gene were determined. Expression
      of a 5'-deletion in both C2C12 and PK-15 cells showed that a negative regulatory
      element was at -1871 to +185 bp and a positive regulatory element was at -1158 to
      +185 bp. Among the different types of muscle fibers, PGM1 had the highest
      expression in both longissimus dorsi and biceps femoris. The expression was
      concentrated in the muscle fibers at different growth stages of Meishan and Large
      White pigs. The synonymous mutation C462T in the coding sequence was confirmed by
      polymerase chain reaction-restriction fragment length polymorphism, and the
      frequency of the C allele was dominant in Chinese indigenous breeds. Association
      analysis with lean meat showed that the C462T site was different. 

PMID- 25867432
TI  - Application of SCAR markers linked with mungbean yellow mosaic virus disease
      resistance gene in Pakistan mungbean germplasm.
AB  - Mungbean yellow mosaic virus disease (MYMVD) caused by single-stranded DNA
      begomovirus is the most prominent threat to the mungbean crop in Pakistan.
      Mungbean genotypes consisting of 127 varieties/lines were screened for MYMVD
      under natural field conditions. No genotypes were found to be immune or highly
      resistant against MYMVD. Genotypes showing resistant and tolerant responses in
      field screening trials were screened using sequence characterized amplified
      region (SCAR) markers linked with the MYMVD-resistance gene. SCAR markers
      amplified the desired band only in the resistant and tolerant genotypes, while no
      amplification was observed in susceptible genotypes. SCAR markers will be useful
      for future breeding and varietal developmental programs and mungbean genotypes
      can be screened on the molecular level. 

PMID- 25867433
TI  - Molecular cloning and characterization, and prokaryotic expression of the GnRH1
      gene obtained from Jinghai yellow chicken.
AB  - The gonadotropin-releasing hormone (GnRH) plays an important role in the control
      of reproductive functions. Recent studies have reported the occurrence of GnRH
      molecular variants in numerous species. In this study, the GnRH1 gene from
      Jinghai yellow chicken was cloned by reverse transcriptase-polymerase chain
      reaction and transformed into BL21 (DE3) competent cells. The GnRH1 gene and
      amino acid sequences were subjected to bioinformatic analyses. The GnRH1 gene
      nucleotide sequence was discovered to be 352 bp long, containing a coding,
      promoter, and section of the 3'-regions. The GnRH1 gene shared 93, 81, 54, 58,
      61, 76, 76, 59, 76, and 66% sequence identity with Meleagris gallopavo, Columba
      livia, Homo sapiens, Bos taurus, swines, Capra hircus, Ovis aries, Pantholops
      hodgsonii, Equus caballus, and Rattus norvegicus, respectively. The GnRH1 gene
      showed conserved domains. The GnRH1 protein was a secreted protein comprising 92
      amino acids, with a molecular weight of 10205.6 Da and a theoretical pI of 5.67.
      Most of the amino acid residues were observed to be hydrophilic, indicating water
      solubility. The predicted secondary structures of proteins included alpha-helices
      (h; 23.08%), beta-extensions (e; 10.92%), and random coils (c; 66.0%). The
      successful construction of prokaryotic expression vector pET32a-GnRH1 was
      confirmed by restriction and sequence analysis. SDS-PAGE analysis showed the
      successful expression of recombinant plasmid in Escherichia coli BL21 (molecular
      weight = 25-28 kDa). Larger quantities of protein were expressed in supernatant,
      indicating greater expression in soluble form. Western blot analysis confirmed
      the expression of the target protein.

PMID- 25867434
TI  - Polymorphisms and allele frequencies of glutathione S-transferases A1 and P1
      genes in the Polish population.
AB  - Glutathione S-transferases (GST) A1 and P1 are crucial enzymes involved in the
      biotransformation of drugs, carcinogens, and toxins, and their activity may
      influence drug response, susceptibility to diseases, and carcinogenesis. The
      genes encoding these enzymes, GSTA1 and GSTP1, have been examined in many studies
      because of their genetic variability, which may affect enzymatic activity. The
      goal of this study was to determine the distribution of the alleles GSTA1*A/*B
      and GSTP1*A, *B, and *C in the Polish population. A total of 160 subjects from
      the Polish population were genotyped for 2 polymorphisms (I105V and A114V) in the
      GSTP1 gene using pyrosequencing. The promoter region of the GSTA1 gene was
      screened using sequencing. The detected variants were subjected to haplotype
      analysis. We found that the distribution of the alleles GSTA1*A/*B and GSTP1*A,
      *B, and *C in the Polish population correspond to the results of studies in
      Caucasians. Furthermore, we identified additional single nucleotide
      polymorphisms, excluding 3 well-known changes (G-52A, C-69T, T-567G), which are
      linked to alleles GSTA1*A/*B, that affect enzyme activity. A total of 4
      haplotypes were identified in 160 Polish individuals. 

PMID- 25867435
TI  - TCF7L2 gene polymorphisms and susceptibility to breast cancer: a meta-analysis.
AB  - Numerous studies have evaluated the association between TCF7L2 gene polymorphisms
      (rs12255372 and rs7903146) and breast cancer risk. However, the results have been
      inconsistent. Therefore, in the current study, we performed a meta-analysis. A
      systematically literature search of the PubMed and EMBASE databases was conducted
      in November 2013, and the reference lists of articles were retrieved. A summary
      odds ratio (OR) with its 95% confidence interval (CI) were calculated to evaluate
      the strength of association. Publication bias was investigated using Begg's
      funnel plot. Meta-analysis was performed using STATA package version 12.0. A
      total of 4 case-control studies met our inclusion criteria, including 4600 cases
      and 5289 controls. Overall, TCF7L2 gene polymorphisms were significantly
      associated with an increased risk of breast cancer in genetic comparison models
      (rs12255372 for GG vs GT: OR = 0.90, 95%CI = 0.83-0.98; rs7903146 for CC vs TT:
      OR = 0.75, 95%CI = 0.63-0.90, CC vs CT: OR = 0.88, 95%CI = 0.81-0.97, dominant
      model: OR = 1.16, 95%CI = 1.06-1.27, recessive model: OR = 0.79, 95%CI = 0.67
      0.94). This meta-analysis demonstrated that TCF7L2 gene polymorphisms (rs12255372
      and rs7903146) are associated with an increased susceptibility to breast cancer.
      However, further studies including large sample sizes are needed to validate this
      association.

PMID- 25867436
TI  - Systematic review on the association between ERCC1 rs3212986 and ERCC2 rs13181
      polymorphisms and glioma risk.
AB  - Several studies have examined the association between excision repair cross
      complementation group 1 (ERCC1) C8092A and ERCC2 Lys751Gln polymorphisms and
      glioma risk, but the results have been inconclusive. We conducted a meta-analysis
      of 12 studies to determine the association between ERCC1 rs3212986 and ERCC2
      rs13181 genes and glioma susceptibility. We searched for relevant studies in both
      Chinese and English in PubMed, Web of Science, Cochrane Library, and EMBASE
      through January 1, 2014, and identified 3939 cases and 5407 controls. The results
      showed that individuals carrying the ERCC1 rs3212986 AA genotype had higher risk
      of glioma compared with the CC genotype, with a pooled odds ratio = 1.29, 95%
      confidence interval = 1.07-1.55. Subgroup analysis showed that the ERCC1
      rs3212986 AA genotype was significantly associated with an increased risk of
      glioma in the Chinese population (odds ratio = 1.37, 95% confidence interval =
      1.07-1.55), but no association in Caucasian Chinese. No significant association
      was observed between ERCC2 rs13181 polymorphisms and glioma risk. The results of
      our meta-analysis strongly suggested that the ERCC1 rs3212986 polymorphism was
      associated with a higher susceptibility to glioma, particularly in the Chinese
      population. Studies including a larger sample size and more specified information
      regarding pathological types of glioma are needed to confirm our results.

PMID- 25867437
TI  - A rapid screening of ancestry for genetic association studies in an admixed
      population from Pernambuco, Brazil.
AB  - Genetic association studies determine how genes influence traits. However, non
      detected population substructure may bias the analysis, resulting in spurious
      results. One method to detect substructure is to genotype ancestry informative
      markers (AIMs) besides the candidate variants, quantifying how much ancestral
      populations contribute to the samples' genetic background. The present study
      aimed to use a minimum quantity of markers, while retaining full potential to
      estimate ancestries. We tested the feasibility of a subset of the 12 most
      informative markers from a previously established study to estimate influence
      from three ancestral populations: European, African and Amerindian. The results
      showed that in a sample with a diverse ethnicity (N = 822) derived from 1000
      Genomes database, the 12 AIMs had the same capacity to estimate ancestries when
      compared to the original set of 128 AIMs, since estimates from the two panels
      were closely correlated. Thus, these 12 SNPs were used to estimate ancestry in a
      new sample (N = 192) from an admixed population in Recife, Northeast Brazil. The
      ancestry estimates from Recife subjects were in accordance with previous studies,
      showing that Northeastern Brazilian populations show great influence from
      European ancestry (59.7%), followed by African (23.0%) and Amerindian (17.3%)
      ancestries. Ethnicity self-classification according to skin-color was confirmed
      to be a poor indicator of population substructure in Brazilians, since ancestry
      estimates overlapped between classifications. Thus, our streamlined panel of 12
      markers may substitute panels with more markers, while retaining the capacity to
      control for population substructure and admixture, thereby reducing sample
      processing time. 

PMID- 25867438
TI  - Microarray analysis of differentially expressed genes in the liver between Bai'er
      layers and broilers.
AB  - In this study, we profiled gene expression in chicken liver and screened
      differentially expressed genes in the Bai'er layers and fat line broilers. Birds
      were derived from the 14th generation of Northeast Agricultural University fat
      broiler lines and Bai'er layers. Chicken genome arrays were used to screen
      differentially expressed genes in liver tissue from the Bai'er layers and fat
      line broilers. We screened 671 differentially expressed genes between broilers
      and layers at the ages of 2 and 4 weeks. We observed enrichment of a series of
      significant pathways, including the mitogen-activated protein kinase signaling
      pathway, cell cycle, mammalian target of rapamycin signaling pathway, and p53
      signaling pathway. At 2 and 4 weeks, 94 shared differentially expressed genes
      were observed. We speculated that these genes regulate chicken lipid metabolism. 

PMID- 25867439
TI  - Detection of hepatitis E virus genome in pig livers in Antioquia, Colombia.
AB  - Hepatitis E is a form of endemic acute hepatitis found in humans in many
      countries worldwide and is caused by the hepatitis E Virus (HEV). Detection of
      HEV in pigs indicates that they may be carriers, possibly through zoonosis. The
      prevalence of HEV in pigs in Colombia is unknown. Studies in the US found that
      11% of pig livers sold in grocery stores are contaminated with HEV. It is also
      known that HEV can be inactivated when cooked, as it is labile to high
      temperatures. The aim of this study was to determine HEV contamination in pig
      livers sold in Medellin, Antioquia. A total of 150 livers from 5 slaughterhouses
      and 100 livers in grocery stores from different social strata of the city of
      Medellin analyzed to detect a segment of the HEV open reading frame-1 using
      reverse transcription-polymerase chain reaction. The results showed that 41.3% of
      pig livers from slaughterhouses and 25% of livers from grocery stores tested
      positive for HEV. Thus, the HEV genome is present in pig livers sold in
      Antioquia, revealing the presence of this virus in pigs from Colombia and the
      need subject entrails to proper cooking processes before consumption. Further
      research is required to determine the role of this virus in public health and
      pork production in Colombia. 

PMID- 25867440
TI  - Association of the IL-4R Q576R polymorphism and asthma in the Chinese Han
      population: a meta-analysis.
AB  - The IL-4R Q576R polymorphism has been reported to increase susceptibility to
      asthma, but the results are controversial. Thus, we performed a meta-analysis to
      evaluate the association of the IL-4R Q576R polymorphism and asthma risk in the
      Chinese Han population. A total of sixteen eligible case-control studies that
      evaluated the relationship between the IL-4R Q576R polymorphism and asthma in the
      Chinese Han population were obtained by comprehensive literature search
      incorporating electronic databases, and included 2077 asthma cases and 1589
      controls. Our analysis detected a significant association between the IL-4R Q576R
      polymorphism and the risk of asthma in the Chinese Han population (Allelic model:
      OR = 1.481, 95%CI = 1.134-1.935, P = 0.004; Dominant model: OR = 1.542, 95%CI =
      1.194-1.990, P = 0.001; Recessive model: OR = 1.695, 95%CI = 1.170-2.456, P =
      0.005, Additive model: OR = 1.897, 95%CI = 1.299-2.771, P = 0.005). The year of
      publication and size of total sample might be sources of between-study
      heterogeneity. Upon subgroup analysis by size of total sample of each study, the
      significant association only remained in a subgroup with a small sample size. In
      summary, our meta-analysis suggested that the IL-4R Q576R polymorphism is
      associated with asthma in the Chinese Han population. 

PMID- 25867441
TI  - Effectiveness of external fixator combined with T-plate internal fixation for the
      treatment of comminuted distal radius fractures.
AB  - This study compared the efficacy between external fixator combined with palmar T
      plate internal fixation and simple plate internal fixation for the treatment of
      comminuted distal radius fractures. A total of 61 patients classified as type C
      according to the AO/ASIF classification underwent surgery for comminuted distal
      radius fractures. There were 54 and 7 cases of closed and open fractures,
      respectively. Moreover, 19 patients received an external fixator combined with T
      plate internal fixation, and 42 received simple plate internal fixation. All
      patients were treated successfully during 12-month postoperative follow-up. The
      follow-up results show that the palmar flexion and dorsiflexion of the wrist,
      radial height, and palmar angle were significantly better in those treated with
      the external fixator combined with T-plate compared to those treated with the
      simple plate only (P < 0.05); however, there were no significant differences in
      radial-ulnar deviation, wrist range of motion, or wrist function score between
      groups (P > 0.05). Hence, the effectiveness of external fixator combined with T
      plate internal fixation for the treatment of comminuted distal radius fractures
      was satisfactory. Patients sufficiently recovered wrist, forearm, and hand
      function. In conclusion, compared to the simple T-plate, the external fixator
      combined with T-plate internal fixation can reduce the possibility of the
      postoperative re-shifting of broken bones and keep the distraction of fractures
      to maintain radial height and prevent radial shortening. 

PMID- 25867442
TI  - Monitoring tissue blood oxygen saturation in the internal jugular venous area
      using near infrared spectroscopy.
AB  - Central venous blood oxygen saturation (ScvO2) is an important monitoring index
      of fluid resuscitation. However, monitoring of ScvO2 is not continuous and
      invasive. Near infrared spectroscopy (NIRS) is an optical technology for the
      noninvasive detection of hemodynamic changes, with advantages of being real-time,
      continuous, low-cost, and portable. The present study aimed to determine whether
      a correlation exists between the tissue blood oxygen saturation in the internal
      jugular venous area (StO2) data obtained with NIRS and the ScvO2 and whether
      these two quantities are equivalent. Data were collected from 13 patients. We
      used ultrasound to locate the placement site for the NIRS light source outside
      the internal jugular vein. Meanwhile, a sample for blood gas analysis was
      obtained through the central venous catheter. A correlation analysis between the
      StO2 and ScvO2 of 13 samples was performed (Pearson correlation coefficient),
      suggesting a high correlation between them (r = 0.906, StO2 =1.0018 ScvO2
      +2.8524). Bland-Altman analysis was also performed between the StO2 and ScvO2.
      Results were as follows: 100% of monitored points fell within the range of the
      mean +/- 1.96 SD of the difference between the StO2 and ScvO2; range of the mean
      +/- 1.96 SD of the difference between the StO2 and ScvO2 was 3 +/- 10.2;
      confidence interval of the difference between the StO2 and ScvO2 was -7.2 to
      13.2%. The StO2 monitored with NIRS correlated highly with the ScvO2 measured in
      the internal jugular vein. Therefore, the StO2 can be used for directing clinical
      treatment with further research.

PMID- 25867443
TI  - Interethnic variation of the MMP-9 microsatellite in Amerindian and Mexican
      Mestizo populations: considerations for genetic association studies.
AB  - We studied the interethnic variation of the MMP-9 microsatellite in the Mestizo
      and Amerindian populations using blood samples collected from 435 healthy
      unrelated individuals from the Central Valley of Mexico. DNA samples were
      genotyped using the -90 (CA)12-27 repeat near the MMP transcriptional start site
      using capillary electrophoresis. Our data were compared with those from African,
      Asian, and European populations (N = 729). Both Mestizo and Amerindian
      populations were in Hardy-Weinberg equilibrium (P >= 0.05). However, strong
      genetic heterogeneity was found within the Mestizo population (94%, P <= 0.0001),
      which exhibited the highest frequency of Amerindian, African, and European
      alleles. Likewise, Amerindians showed 6.7% variation among populations (P <=
      0.0001), suggesting a genetic substructure potentially associated with linguistic
      affiliations. These findings were corroborated with principal component and
      population differentiation analyses, which showed relative proximity among the
      Mestizos and their historical parental populations: Asian (FST >= 0.05), European
      (FST >= 0.09), and African (FST >= 0.02). Nevertheless, important differences
      were found between Mestizo and Nahuas (P <= 0.0001), and between Mestizo and
      Me'Phaas (P <= 0.0001). These findings highlight the importance of determining
      local-specific patterns to establish the population variability of MMP-9 and
      other polymorphic markers. Validation of candidate markers is critical to
      identifying risk factors; however, this depends on knowledge of population
      genetic variation, which increases the possibility of finding true causative
      variants. We also show that dissimilar ethnic backgrounds might lead to spurious
      associations. Our study provides useful considerations for greater accuracy and
      robustness in future genetic association studies. 

PMID- 25867444
TI  - An in vitro enzymatic assay to measure transcription inhibition by gallium(III)
      and H3 5,10,15-tris(pentafluorophenyl)corroles.
AB  - Chemotherapy often involves broad-spectrum cytotoxic agents with many side
      effects and limited targeting. Corroles are a class of tetrapyrrolic macrocycles
      that exhibit differential cytostatic and cytotoxic properties in specific cell
      lines, depending on the identities of the chelated metal and functional groups.
      The unique behavior of functionalized corroles towards specific cell lines
      introduces the possibility of targeted chemotherapy. Many anticancer drugs are
      evaluated by their ability to inhibit RNA transcription. Here we present a step
      by-step protocol for RNA transcription in the presence of known and potential
      inhibitors. The evaluation of the RNA products of the transcription reaction by
      gel electrophoresis and UV-Vis spectroscopy provides information on inhibitive
      properties of potential anticancer drug candidates and, with modifications to the
      assay, more about their mechanism of action. Little is known about the molecular
      mechanism of action of corrole cytotoxicity. In this experiment, we consider two
      corrole compounds: gallium(III) 5,10,15-(tris)pentafluorophenylcorrole (Ga(tpfc))
      and freebase analogue 5,10,15-(tris)pentafluorophenylcorrole (tpfc). An RNA
      transcription assay was used to examine the inhibitive properties of the
      corroles. Five transcription reactions were prepared: DNA treated with
      Actinomycin D, triptolide, Ga(tpfc), tpfc at a [complex]:[template DNA base]
      ratio of 0.01, respectively, and an untreated control. The transcription
      reactions were analyzed after 4 hr using agarose gel electrophoresis and UV-Vis
      spectroscopy. There is clear inhibition by Ga(tpfc), Actinomycin D, and
      triptolide. This RNA transcription assay can be modified to provide more
      mechanistic detail by varying the concentrations of the anticancer complex, DNA,
      or polymerase enzyme, or by incubating the DNA or polymerase with the complexes
      prior to RNA transcription; these modifications would differentiate between an
      inhibition mechanism involving the DNA or the enzyme. Adding the complex after
      RNA transcription can be used to test whether the complexes degrade or hydrolyze
      the RNA. This assay can also be used to study additional anticancer candidates. 

PMID- 25867445
TI  - Analysis of small interfering RNA by capillary electrophoresis in
      hydroxyethylcellulose solutions.
AB  - The analysis of small interfering RNA (siRNA) is important for gene function
      studies and drug developments. We employed CE to study the separation of siRNA
      ladder marker, which were ten double-stranded RNA (dsRNA) fragments ranged from
      20 to 1000 bp, in solutions of hydroxyethylcellulose (HEC) polymer with different
      concentrations and molecular weights (Mws). Migration mechanism of dsRNA during
      CE was studied by the mobility and resolution length (RL) plots. We found that
      the RL depended on not only the concentration of HEC, but also the Mw of HEC. For
      instance, RL of small dsRNA fragment was more influenced by concentration of high
      Mw HEC than large dsRNA fragment and RL of large dsRNA fragment was more
      influenced by concentration of low Mw HEC than small dsRNA fragment. In addition,
      we found electrophoretic evidence that the structure of dsRNA was more compact
      than dsDNA with the same length. In practice, we succeeded to separate the
      glyceraldehyde 3-phosphate dehydrogenase siRNA in the mixture of the siRNA ladder
      marker within 4 min. 

PMID- 25867446
TI  - Rapid response in psychological treatments for binge eating disorder.
AB  - OBJECTIVE: Analysis of short- and long-term effects of rapid response across 3
      different treatments for binge eating disorder (BED). METHOD: In a randomized
      clinical study comparing interpersonal psychotherapy (IPT), cognitive-behavioral
      therapy guided self-help (CBTgsh), and behavioral weight loss (BWL) treatment in
      205 adults meeting Diagnostic and Statistical Manual of Mental Disorders (4th
      ed.; DSM-IV; APA, 1994) criteria for BED, the predictive value of rapid response,
      defined as >=70% reduction in binge eating by Week 4, was determined for
      remission from binge eating and global eating disorder psychopathology at
      posttreatment, 6-, 12-, 18-, and 24-month follow-ups. RESULTS: Rapid responders
      in CBTgsh, but not in IPT or BWL, showed significantly greater rates of remission
      from binge eating than nonrapid responders, which was sustained over the long
      term. Rapid and nonrapid responders in IPT and rapid responders in CBTgsh showed
      a greater remission from binge eating than nonrapid responders in CBTgsh and BWL.
      Rapid responders in CBTgsh showed greater remission from binge eating than rapid
      responders in BWL. Although rapid responders in all treatments had lower global
      eating disorder psychopathology than nonrapid responders in the short term, rapid
      responders in CBTgsh and IPT were more improved than those in BWL and nonrapid
      responders in each treatment. Rapid responders in BWL did not differ from
      nonrapid responders in CBTgsh and IPT. CONCLUSION: Rapid response is a treatment
      specific positive prognostic indicator of sustained remission from binge eating
      in CBTgsh. Regarding an evidence-based, stepped-care model, IPT, equally
      efficacious for rapid and nonrapid responders, could be investigated as a second
      line treatment in case of nonrapid response to first-line CBTgsh.

PMID- 25867448
TI  - Motivational deficits differentially predict improvement in a randomized trial of
      self-system therapy for depression.
AB  - OBJECTIVE: A randomized trial compared the time course and differential
      predictors of symptom improvement in 2 treatments for depression. METHOD: Forty
      nine adults (84% female) who were not taking antidepressant medications and met
      diagnostic criteria for major depressive disorder or dysthymia were randomly
      assigned either to cognitive-behavioral therapy (CBT) or self-system therapy
      (SST), a treatment that targets problems in self-regulation, the ongoing process
      of evaluating progress toward personal goals. Self-regulatory variables
      (promotion and prevention focus and goal disengagement and reengagement) were
      assessed as potential moderators of efficacy. At intake, most participants
      reported depression in the moderate to severe range and had histories of
      recurrent episodes and previous treatment attempts. Self-reported symptoms of
      depression and anxiety were assessed at each therapy session. Multilevel modeling
      was used to examine (a) differences in change associated with the treatment
      conditions and (b) moderation of treatment efficacy by pretreatment measures of
      self-regulatory deficits. RESULTS: Both treatments were effective and did not
      show differences in the magnitude or rate of symptom change or in dropout rates,
      suggesting that CBT and SST were equally effective in improving depression and
      anxiety. Patients with self-regulatory deficits, however, showed greater
      improvement in depressive symptoms with SST. Specifically, patients with low
      promotion focus and low goal reengagement responded better to SST, whereas
      patients with high prevention focus responded better to CBT. CONCLUSIONS:
      Overall, the results corroborate previous research suggesting that SST is a
      viable short-term treatment for depression that is particularly effective in
      helping patients compensate for self-regulatory deficits.

PMID- 25867447
TI  - Paths to tobacco abstinence: A repeated-measures latent class analysis.
AB  - OBJECTIVE: Knowledge of smoking change processes may be enhanced by identifying
      pathways to stable abstinence. We sought to identify latent classes of smokers
      based on their day-to-day smoking status in the first weeks of a cessation
      attempt. We examined treatment effects on class membership and compared classes
      on baseline individual differences and 6-month abstinence rates. METHOD: In this
      secondary analysis of a double-blind randomized placebo-controlled clinical trial
      (N = 1,433) of 5 smoking cessation pharmacotherapies (nicotine patch, nicotine
      lozenge, bupropion SR, patch and lozenge, or bupropion SR and lozenge), we
      conducted repeated-measures latent class analysis of daily smoking status (any
      smoking vs. none) for the first 27 days of a quit attempt. Treatment and
      covariate relations with latent class membership were examined. Distal outcome
      analysis compared confirmed 6-month abstinence rates among the latent classes.
      RESULTS: A 5-class solution was selected. Three-quarters of smokers were in
      stable smoking or abstinent classes, but 25% were in classes with unstable
      abstinence probabilities over time. Active treatment (compared to placebo), and
      particularly the patch and lozenge combination, promoted early quitting. Latent
      classes differed in 6-month abstinence rates and on several baseline variables,
      including nicotine dependence, quitting history, self-efficacy, sleep
      disturbance, and minority status. CONCLUSIONS: Repeated-measures latent class
      analysis identified latent classes of smoking change patterns affected by
      treatment, related to known risk factors, and predictive of distal outcomes.
      Tracking behavior early in a change attempt may identify prognostic patterns of
      change and facilitate adaptive treatment planning.

PMID- 25867449
TI  - Rational Design of Adjuvant for Skin Delivery: Conjugation of Synthetic beta
      Glucan Dectin-1 Agonist to Protein Antigen.
AB  - The potential benefits of skin delivery of vaccines derive from the presence of a
      densely connected network of antigen presenting cells in the skin layer, most
      significantly represented by Langerhans cells and dermal dendritic cells.
      Targeting these cells by adjuvant conjugated to an antigen should result in
      enhanced immunogenicity of a vaccine. Since one of the most widely used adjuvants
      is an insoluble salt of aluminum (aluminum hydroxide) that cannot be used for
      skin delivery due to reactogenicity, we focused our attention on agonists of
      receptors present on skin dendritic cells, including the Dectin-1 receptor. beta
      (1-3)-glucans, which are the most abundant components of the fungal surface, are
      known to activate the innate immune response by interaction with the C-type
      lectin-like Dectin-1 receptor. In this work we identified by rational design a
      well-defined synthetic beta-(1-3)-glucan hexasaccharide as a Dectin-1 agonist and
      chemically conjugated it to the genetically detoxified diphtheria toxin (CRM197)
      protein antigen, as a means to increase the binding to Dectin-1 receptor and to
      target to skin dendritic cells. We demonstrated that the in vitro activation of
      the receptor was significantly impacted by the presentation of the glucan on the
      protein carrier. In vivo results in mice showed that the conjugation of the
      synthetic beta-(1-3)-glucan when delivered intradermally resulted in higher
      antibody titers in comparison to intramuscular (i.m.) immunization and was not
      different from subcutaneous (s.c.) delivery. These findings suggest that weak
      receptor binders can be turned into more potent agonists by the multivalent
      presentation of many ligands covalently conjugated to the protein core. Moreover,
      this approach is particularly valuable to increase the immunogenicity of antigens
      administered via skin delivery. 

PMID- 25867450
TI  - Mass-tag enhanced immuno-laser desorption/ionization mass spectrometry for
      sensitive detection of intact protein antigens.
AB  - A new read-out method for antibody arrays using laser desorption/ionization-mass
      spectrometry (LDI-MS) is presented. Small, photocleavable reporter molecules with
      a defined mass called "mass-tags" are used for detection of immunocaptured
      proteins from human plasma. Using prostate specific antigen (PSA), a biomarker
      for prostate cancer, as a model antigen, a high sensitivity generic detection
      methodology based immunocapture with a primary antibody and with a biotin labeled
      secondary antibody coupled to mass-tagged avidin is demonstrated. As each
      secondary antibody can bind several avidin molecules, each having a large number
      of mass-tags, signal amplification can be achieved. The developed PSA sandwich
      mass-tag analysis method provided a limit of detection below 200 pg/mL (6 pM) for
      a 10 MUL plasma sample, well below the clinically relevant cutoff value of 3-4
      ng/mL. This brings the limit of detection (LOD) for detection of intact antigens
      with matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS)
      down to levels comparable to capture by anti-peptide antibodies selected reaction
      monitoring (SISCAPA SRM) and enzyme linked immunosorbent assay (ELISA), as 6 pM
      corresponds to a maximal amount of 60 amol PSA captured on-spot. We propose the
      potential use of LDI (laser desorption/ionization) with mass-tag read-out
      implemented in a sandwich assay format for low abundant and/or early disease
      biomarker detection. 

PMID- 25867451
TI  - Mediobasal and lateral temporal gliomas exhibit different growth patterns,
      surgical outcomes and prognoses.
AB  - OBJECTIVE: This study was aimed at investigating the differences between
      mediobasal temporal gliomas and lateral temporal gliomas. METHODS: One hundred
      and forty-seven patients with temporal gliomas who were admitted in the
      Department of Supratentorial Neoplasms at Beijing Tiantan Hospital between 2008
      and 2011 were included in this prospective study. Temporal gliomas involving the
      limbic and paralimbic systems were classified as mediobasal temporal gliomas
      (MTGs), while those without the involvement of the limbic and paralimbic systems
      were defined as lateral temporal gliomas (LTGs). The clinical, radiological,
      histopathological, and molecular features were compared between MTG and LTG
      patients. RESULTS: Compared to LTGs, MTGs were significantly larger in size (P =
      0.013) and displayed a more aggressive invasion of surrounding tissues (P <
      0.001). Marginally significant differences of the IDH1/2 mutation rate were
      observed between MTG and LTG patients (P = 0.058). The postoperative disability
      rate of MTGs was significantly higher than that of LTGs (P = 0.031). Resection
      degree according to tumor grade between LTG and MTG showed no statistical
      significance, while it mixed all grades showed marginally significant difference
      (P = 0.060). Regardless of tumor grade, the PFS and OS of MTG was shorter than
      that of LTG, except for OS in grade II (P = 0.189). CONCLUSIONS: Temporal gliomas
      can be classified into two types, MTG and LTG which have different growth
      patterns, surgical outcomes and prognoses. Due to the significantly worse
      prognosis of patients with MTGs, this classification is useful for the clinical
      prognostic prediction of temporal gliomas.

PMID- 25867452
TI  - Tuberculosis of the spine--Prospective neurological and patient reported outcome
      study.
AB  - OBJECTIVE: To prospectively investigate the rate of neurological recovery and
      patient reported outcome of tuberculosis (TB) spine patients following surgery at
      a tertiary referral hospital. TB spine remains a major cause of neurological
      impairment in the developing world fuelled by poor socio-economic conditions and
      HIV co-infection. Although numerous retrospective studies are available, there is
      a paucity of prospective data regarding rate of neurological improvement and
      patient reported outcome. METHODS: Twenty adult patients were prospectively
      recruited. The average age was 44.5 years. Half had co-existent HIV infection.
      All patients underwent decompressive surgery utilising a variety of anterior and
      posterior procedures. All received a minimum of 9 months TB medication. They were
      followed up at 4, 8, 12, 26 and 52 weeks post operatively. Neurological status
      was monitored by Nurick, mJOA and ASIA systems. Patient reported outcome was
      monitored by SF36 questionnaires at all-time points. RESULTS: All patients
      improved neurologically including 4 ASIA A's. By last follow up, 17 could walk as
      opposed to 5 pre-op. The Nurick average score improved from 5.5 to 1.9 and the
      mJOA lower limb score 1.8-5.5. The SF36 improved from 31 to 62 over the year with
      the biggest gains occurring after 3 months. This was confirmed in all domains
      except pain and social, which improved earlier. CONCLUSIONS: There is a positive
      prognosis for neurological outcome in TB spine following a variety of surgical
      decompressive procedures and medical therapy. The majority of the recovery occurs
      after the 3 months post-operative mark.

PMID- 25867453
TI  - The gadolinium-based contrast agent Omniscan(r) promotes in vitro fibroblast
      survival through in situ precipitation.
AB  - The current study aims to explore how the gadolinium (Gd)-based contrast agent
      (GBCA) Omniscan(r) enhanced cell viability of murine fibroblasts. The results of
      scanning electron microscopy showed that Omniscan(r) can precipitate in cell
      culture media and deposit on cell membranes. Energy-dispersive X-ray analysis and
      Fourier-transform infrared spectroscopy demonstrated the presence of Gd and
      phosphates in the agglomerated particles. By filtering the Omniscan(r)-containing
      medium through a 220 nm filter, it can be clearly found that the increased cell
      viability should be mainly attributed to the insoluble species of gadolinium
      rather than to chelated gadolinium. Moreover, the effects of other gadolinium
      based contrast agents, Magnevist(r) and Dotarem(r), were compared with that of
      Omniscan(r). It is noted that the three contrast agents differed in their ability
      to induce cell viability, which is possibly ascribed to the different chemical
      stabilities of gadolinium chelates as demonstrated by the attenuation in cell
      growth upon the addition of excess ligands to the compounds. The results of flow
      cytometry analysis also showed that Omniscan(r) can promote cell growth via an
      increase in the S-phase cell population as evidenced by the elevated levels of
      cell cycle associated proteins cyclin D, cyclin A and the phosphorylated Rb
      protein. Furthermore, our results revealed that integrin-mediated signaling may
      play an important role in both Omniscan(r) and Magnevist(r)-enhanced focal
      adhesion formation since the blockade of integrins decreased the level of ERK
      phosphorylation induced by the two GBCAs. Taken together, these data suggested
      that in situ gadolinium phosphate precipitation formation mediated Omniscan(r)
      promoted fibroblast survival, which is similar to that of gadolinium chloride. It
      was demonstrated that the application of GBCAs with more stable thermodynamic
      stability may cause less dissociation of the gadolinium ion and thus resulted in
      less precipitation, finally leading to lower occurrence of nephrogenic systemic
      fibrosis. The obtained results would also be helpful for the development of safe
      gadolinium-based contrast agents. 

PMID- 25867454
TI  - Methods of Reprogramming to Induced Pluripotent Stem Cell Associated with
      Chromosomal Integrity and Delineation of a Chromosome 5q Candidate Region for
      Growth Advantage.
AB  - Induced pluripotent stem cells (iPSCs) have brought great promises for disease
      modeling and cell-based therapies. One concern related to the use of reprogrammed
      somatic cells is the loss of genomic integrity and chromosome stability, a
      hallmark for cancer and many other human disorders. We investigated 16 human iPSC
      lines reprogrammed by nonintegrative Sendai virus (SeV) and another 16 iPSC lines
      generated by integrative lentivirus for genetic changes. At early passages we
      detected cytogenetic rearrangements in 44% (7/16) of iPSC lines generated by
      lentiviral integration whereas the corresponding figure was 6% (1/16) using SeV
      based delivery. The rearrangements were numerical and/or structural with
      chromosomes 5 and 12 as the most frequently involved chromosomes. Three iPSC
      lines with chromosome 5 aberrations were derived from one and the same donor. We
      present in this study the aberrant karyotypes including a duplication of
      chromosome 5q13q33 that restricts a candidate region for growth advantage. Our
      results suggest that the use of integrative lentivirus confers a higher risk for
      cytogenetic abnormalities at early passages when compared to SeV-based
      reprogramming. In combination, our findings expand the knowledge on acquired
      cytogenetic aberrations in iPSC after reprogramming and during culture. 

PMID- 25867455
TI  - Quantitative 3D Fluorescence Imaging of Single Catalytic Turnovers Reveals
      Spatiotemporal Gradients in Reactivity of Zeolite H-ZSM-5 Crystals upon Steaming.
AB  - Optimizing the number, distribution, and accessibility of Bronsted acid sites in
      zeolite-based catalysts is of a paramount importance to further improve their
      catalytic performance. However, it remains challenging to measure real-time
      changes in reactivity of single zeolite catalyst particles by ensemble-averaging
      characterization methods. In this work, a detailed 3D single molecule, single
      turnover sensitive fluorescence microscopy study is presented to quantify the
      reactivity of Bronsted acid sites in zeolite H-ZSM-5 crystals upon steaming. This
      approach, in combination with the oligomerization of furfuryl alcohol as a probe
      reaction, allowed the stochastic behavior of single catalytic turnovers and
      temporally resolved turnover frequencies of zeolite domains smaller than the
      diffraction limited resolution to be investigated with great precision. It was
      found that the single turnover kinetics of the parent zeolite crystal proceeds
      with significant spatial differences in turnover frequencies on the nanoscale and
      noncorrelated temporal fluctuations. Mild steaming of zeolite H-ZSM-5 crystals at
      500  degrees C led to an enhanced surface reactivity, with up to 4 times higher
      local turnover rates than those of the parent H-ZSM-5 crystals, and revealed
      remarkable heterogeneities in surface reactivity. In strong contrast, severe
      steaming at 700  degrees C significantly dealuminated the zeolite H-ZSM-5
      material, leading to a 460 times lower turnover rate. The differences in measured
      turnover activities are explained by changes in the 3D aluminum distribution due
      to migration of extraframework Al-species and their subsequent effect on pore
      accessibility, as corroborated by time-of-flight secondary ion mass spectrometry
      (TOF-SIMS) sputter depth profiling data. 

PMID- 25867456
TI  - Ectopic intravagal parathyroid adenoma.
AB  - BACKGROUND: Intraneural parathyroid adenomas are rare, with only 9 cases of
      intravagal adenomas reported. All but one of the reported cases was found after
      multiple neck explorations. To the best of our knowledge, we report the first
      case of nonsupernumerary ectopic intravagal parathyroid identified at primary
      exploration. METHODS AND RESULTS: A 17-year-old girl with primary
      hyperparathyroidism and nephrolithiasis was referred with a sestamibi scan
      reporting a left lower parathyroid adenoma. No eutopic parathyroid tissue was
      identified during full exploration of the left side of the neck. Exploration of
      the carotid sheath revealed a fusiform swelling of the vagus nerve at the level
      of the carotid bifurcation. Longitudinal incision of the vagal perineurium
      revealed a 7-mm parathyroid adenoma, which was enucleated. The patient recovered
      uneventfully, with normalization of serum calcium, parathyroid hormone (PTH), and
      normal vocal cord function. CONCLUSION: We believe that this is the first
      reported case of nonsupernumerary intravagal parathyroid adenoma resected at
      initial exploration. The vagus nerve is a rare location for a parathyroid
      adenoma, but one that should be considered, even during primary exploration.

PMID- 25867457
TI  - Sex-dependent effects of ultraviolet radiation on the marine amphipod Ampithoe
      valida (Ampithoidae).
AB  - The combined effects of solar radiation and diet on the marine amphipod Ampithoe
      valida were investigated exposing individuals to two solar radiation treatments:
      PAB (>280 nm, PAR+UV-A+UV-B) and P (>400 nm, only PAR), and three diets: poor
      (Ulva rigida) and rich (Porphyra columbina) in UV-absorbing compounds (UVAC), and
      mixed diet: (U. rigida+P. columbina). Females of A. valida showed higher food
      consumption rates when diets contained P. columbina, and preferred this
      macroalgae rather than U. rigida, resulting in a higher content of UVAC in their
      bodies. Moreover, the content of UVAC increased in the PAB treatment, thus
      suggesting the existence of a mechanism to accumulate these compounds under UVR.
      Although UVR affected the survival, the highest mortality rates were found in
      those females fed with poor-UVAC diets, which evidence that UVAC provided partial
      protection against UVR. Males preferred mixed diet, and did not show preference
      for any particular macroalgae. No differences in mortality were observed between
      radiation treatments, indicating that UVR did not affect the survival of males,
      independently if they accumulated UVAC or not. The vulnerability of females to
      UVR would be partially determined by the type of food consumed, which in turn
      would be closely related to the macroalgae composition of the intertidal they
      inhabiting. These effects could be even more pronounced under a global change
      scenario.

PMID- 25867458
TI  - Generation and grafting of tissue-engineered vessels in a mouse model.
AB  - The construction of vascular conduits is a fundamental strategy for surgical
      repair of damaged and injured vessels resulting from cardiovascular diseases. The
      current protocol presents an efficient and reproducible strategy in which
      functional tissue engineered vessel grafts can be generated using partially
      induced pluripotent stem cell (PiPSC) from human fibroblasts. We designed a
      decellularized vessel scaffold bioreactor, which closely mimics the matrix
      protein structure and blood flow that exists within a native vessel, for seeding
      of PiPSC-endothelial cells or smooth muscle cells prior to grafting into mice.
      This approach was demonstrated to be advantageous because immune-deficient mice
      engrafted with the PiPSC-derived grafts presented with markedly increased
      survival rate 3 weeks after surgery. This protocol represents a valuable tool for
      regenerative medicine, tissue engineering and potentially patient-specific cell
      therapy in the near future. 

PMID- 25867459
TI  - Phosphatidylinositol-glycan-phospholipase D is involved in neurodegeneration in
      prion disease.
AB  - PrPSc is formed from a normal glycosylphosphatidylinositol (GPI)-anchored prion
      protein (PrPC) by a posttranslational modification. Most GPI-anchored proteins
      have been shown to be cleaved by GPI phospholipases. Recently, GPI-phospholipase
      D (GPI-PLD) was shown to be a strictly specific enzyme for GPI anchors. To
      investigate the involvement of GPI-PLD in the processes of neurodegeneration in
      prion diseases, we examined the mRNA and protein expression levels of GPI-PLD in
      the brains of a prion animal model (scrapie), and in both the brains and
      cerebrospinal fluids (CSF) of sporadic and familial Creutzfeldt-Jakob disease
      (CJD) patients. We found that compared with controls, the expression of GPI-PLD
      was dramatically down-regulated in the brains of scrapie-infected mice,
      especially in the caveolin-enriched membrane fractions. Interestingly, the
      observed decrease in GPI-PLD expression levels began at the same time that PrPSc
      began to accumulate in the infected brains and this decrease was also observed in
      both the brain and CSF of CJD patients; however, no differences in expression
      were observed in either the brains or CSF specimens from Alzheimer's disease
      patients. Taken together, these results suggest that the down-regulation of GPI
      PLD protein may be involved in prion propagation in the brains of prion diseases.

PMID- 25867460
TI  - Polyneuropathy with anti-sulfatide and anti-MAG antibodies: clinical,
      neurophysiological, pathological features and response to treatment.
AB  - IgM paraproteins often present reactivity to myelin-associated glycoprotein (MAG)
      and sulfatide. We describe the clinical and neurophysiological findings, and
      therapy response in 21 patients with IgM paraproteinemic neuropathy (15 with anti
      MAG antibodies, 1 with anti-sulfatide antibodies, and 5 with both reactivity),
      and in 2 with anti-sulfatide positivity and no hematological disease. All
      patients complained of sensory symptoms, the majority had demyelinating
      neuropathy. Indirect immunofluorescence on human normal sural nerves disclosed
      different staining patterns. Eight of 13 patients (6 anti-MAG, 1 anti-sulfatide,
      1 both anti-sulfatide and anti-MAG antibodies) improved after Rituximab. IVIg,
      steroids and plasma-exchange were also administered with different responses. 

PMID- 25867461
TI  - Decreased concentration of Klotho in the cerebrospinal fluid of patients with
      relapsing-remitting multiple sclerosis.
AB  - Recent investigations support that an anti-aging protein, namely Klotho, protects
      neurons against the oxidative stress and demyelination. We evaluated the protein
      concentration of Klotho and total anti-oxidant capacity (TAC) in the
      cerebrospinal fluid (CSF) of patients with relapsing-remitting multiple sclerosis
      (RRMS). Klotho concentration and TAC were significantly lower in patients as
      compared to controls. Klotho values showed a significant negative correlation
      with expanded disability status scale (EDSS). Moreover, a significantly positive
      correlation between TAC levels and Klotho concentrations was detected. Klotho may
      play an important role in the pathogenesis of MS, at least in part, through the
      regulation of redox system. 

PMID- 25867462
TI  - Evaluation of the effects of Eserine and JWH-133 on brain dysfunction associated
      with experimental endotoxemia.
AB  - Sepsis is associated with neuronal damage and cognitive impairment, with the
      participation of pro-inflammatory cytokines and oxidative-nitrous stress. It is
      known that activated microglia plays a vital role in neuro-inflammation and neuro
      degeneration. Thus, the objective of this study was to evaluate therapeutic roles
      of two microglia regulating agents, JWH-133 and Eserine, on the neuroinflammatory
      associated brain dysfunctions. To achieve our aim, we used control rats or
      submitted rats to lipopolysaccharide (LPS) challenge. 30 min after LPS challenge,
      the animals received either saline, Eserine, JWH-133 or Eserine+JWH-133. After
      24h, animals were submitted to the habituation to T maze, Rotarod and activity
      cage tests. The rats were killed after and were evaluated for central and
      peripheral inflammatory and oxidative parameters. We observed that the use of
      Eserine, JWH-133 or Eserine + JWH-133 reverted the increases in the inflammatory
      markers [interleukin 6 (IL6), vascular cell adhesion molecule 1(VCAM-1) and
      Eselectin] and oxidative-nitrous stress MDM, and that the anti-inflammatory,
      antioxidant properties of both JWH-133 and Eserine successfully improve the LPS
      induced brain dysfunction. CONCLUSIONS: The results observed in this study
      reinforce the role of microglia activation regulating agents, in particular, JWH
      133 and Eserine, in the brain dysfunction associated with endotoxemia.

PMID- 25867463
TI  - Clinical manifestations of patients with CASPR2 antibodies.
AB  - Contactin-associated protein-like 2 (CASPR2) is one of the target antigens of
      voltage-gated potassium channels (VGKC) complex antibodies. There has been
      relatively little information in the literature regarding CASPR2 autoimmunity,
      especially in Asian population. We investigated the presence of CASPR2 antibodies
      in patients with presumed autoimmune neurological disorders and described the
      clinical features, laboratory findings, and responses to immunotherapy. Five
      patients were identified to be positive for CASPR2 antibodies. The results
      obtained here suggested that CASPR2 antibodies might be the possible cause of
      epilepsy even in the absence of typical features of limbic encephalitis and that
      immunotherapy could provide a favorable outcome. 

PMID- 25867464
TI  - Smoking worsens multiple sclerosis prognosis: two different pathways are
      involved.
AB  - Smoking worsens multiple sclerosis (MS) prognosis. Our study provides evidence
      that indoleamine 2,3-dioxygenase activity is reduced in MS patients who smoke,
      leading to increased production of IL-6 and IL-13. Additionally, both degree of
      expression and renin-angiotensin system activity levels were increased in MS
      patients who smoked, inducing increase in IL-17 and IL-22-producing cell numbers
      as well as significantly greater production of CCL2, CCL3 and CXCL10 chemokines
      by monocytes. Finally, both pathways contributed to a significant decrease in the
      number of CD4+CD25+FoxP3+ regulatory T cells in MS patients who smoked. Both
      pathways could be responsible for the association between smoking and MS risk. 

PMID- 25867465
TI  - Anti-AMPA receptor encephalitis associated with thymomatous myasthenia gravis.
AB  - No thymomatous myasthenia gravis (TMG) has been reported in patients with anti
      alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor encephalitis
      (AMPAR-E). We described clinical presentation and autoimmune profile of the first
      case with both AMPAR-E and TMG. Clinical information was obtained from original
      medical records. Antibodies against AMPAR and confounding antigens were examined
      on transfected human embryonic kidney 293 cells by the indirect
      immunofluorescence method. In this case, anti-AMPAR antibodies and anti
      acetylcholine receptor (AchR) antibodies were both positive and could explain the
      encephalitis and MG respectively. This report also indicated the complexity of
      autoimmunity network associated with thymoma. However, the relationships between
      thymoma, MG and AMPAR-E remained unclear. 

PMID- 25867466
TI  - Anti-thyroid antibodies and cerebrospinal fluid findings in neuromyelitis optica
      spectrum disorders.
AB  - OBJECTIVE: To determine the differences of thyroid diseases and ATAbs in multiple
      sclerosis (MS) and NMOSDs, and to assess the independent impact factors of
      longitudinally extensive transverse myelitis (LETM) in NMOSDs. RESULTS: Anti
      thyroid peroxidase antibodies-positive (TPOAb(+)) and anti-thyroglobulin
      antibodies-positive (TGAb(+)) were most frequent in NMOSDs. LETM and lesions >=6
      vertebral segments were more frequent in TPOAb(+) NMOSDs than in TPOAb-negative
      (TPOAb(-)) NMOSDs. TGAb(+) NMOSDs with LETM were significantly more frequent than
      TGAb-negative (TGAb(-)) NMOSDs. TPOAb(+) and cerebrospinal fluid (CSF)
      abnormalities were independently associated with LETM. CONCLUSIONS: Our findings
      demonstrate that ATAbs and thyroid diseases are significantly different in MS and
      NMOSD patients and CSs. TPOAb(+) and CSF abnormalities may be possible predictors
      of the severity of spinal cord lesions.

PMID- 25867467
TI  - Associations between changes in ferritin levels and susceptibility-weighted
      imaging filtered phase in patients with relapsing-remitting multiple sclerosis
      over 24 weeks of therapy with subcutaneous interferon beta-1a three times weekly.
AB  - Subanalysis of a pilot study (NCT01085318) assessed correlations between serum
      ferritin and imaging assessments in relapsing-remitting multiple sclerosis
      patients (n = 23) receiving 44 MUg interferon beta-1a subcutaneously three times
      weekly. At baseline, 12, and 24 weeks, mean ferritin was 75, 127 (p < 0.001 vs
      baseline), and 101 (p=0.020 vs baseline) ng/mL. No relationship between ferritin
      and susceptibility-weighted imaging (SWI)-filtered phase of subcortical deep gray
      matter was found. Increasing ferritin correlated with decreasing lesion numbers
      on both fluid attenuated inversion recovery and SWI phase at 12 weeks (r = -0.62;
      p = 0.003; n = 21), and with decreasing gadolinium-enhancing lesion volume at 24
      weeks (r = -0.71; p = 0.050; n = 8).

PMID- 25867468
TI  - Regulatory function of CD4+CD25++ T cells in patients with myasthenia gravis is
      associated with phenotypic changes and STAT5 signaling: 1,25-Dihydroxyvitamin D3
      modulates the suppressor activity.
AB  - Regulatory T cells were investigated in early-onset (EO) and late-onset (LO)
      myasthenia gravis patients with anti-acetylcholine receptor antibody (AChR-MG).
      Alterations in PD-1 and PD-L1 on CD4(+)CD25(++) (Treg) and responder T cells
      (Tresp, CD4(+)CD25(-)) were observed in LOMG patients. GITR was decreased on
      CD4(+)CD25(++) of all patients. Decrease of FOXP3 was associated with lower
      phosphorylation of STAT5.1,25-dihydroxyvitamin D3 (VitD3) increased suppression
      in co-culture with a stronger effect in patients by acting possibly both on cell
      groups. Changes in surface molecules and intracellular pathways contribute to the
      defects of Treg in non-thymomatous AChR-MG and VitD3 can have modulatory effects.

PMID- 25867469
TI  - Low and high doses of ursolic acid ameliorate experimental autoimmune myasthenia
      gravis through different pathways.
AB  - Myasthenia gravis (MG) is an autoimmune disease characterized by fatigable muscle
      weakness. Ursolic acid (UA) is a pentacyclic triterpenoid with anti-inflammatory
      and immunomodulatory properties, especially inhibiting IL-17. We found that UA
      ameliorated the symptoms of experimental autoimmune myasthenia gravis (EAMG), a
      rat model of MG. Although both the low and high doses of UA shifted Th17 to Th2
      cytokines, other mechanisms were dose dependent. The low dose enhanced Fas
      mediated apoptosis, whereas the high dose up-regulated Treg cells and reduced the
      concentrations of IgG2b antibodies. These findings suggest a new strategy to
      treat EAMG and even human MG. 

PMID- 25867470
TI  - IgG1 deficiency exacerbates experimental autoimmune myasthenia gravis in BALB/c
      mice.
AB  - Myasthenia gravis is an autoimmune disease characterized by muscle weakness due
      to neuromuscular junction (NMJ) damage by anti-acetylcholine receptor (AChR) auto
      antibodies and complement. In experimental autoimmune myasthenia gravis (EAMG),
      which is induced by immunization with Torpedo AChR in CFA, anti-AChR IgG2b and
      IgG1 are the predominant isotypes in the circulation. Complement activation by
      isotypes such as IgG2b plays a crucial role in EAMG pathogenesis; this suggested
      the possibility that IgG1, which does not activate complement through the
      classical pathway, may suppress EAMG. In this study, we show that AChR-immunized
      BALB/c mice genetically deficient for IgG1 produce higher levels of complement
      activating isotypes of anti-AChR, especially IgG3 and IgG2a, and develop
      increased IgG3/IgG2a deposits at the NMJ, as compared to wild type (WT) BALB/c
      mice. Consistent with this, AChR-immunized IgG1(-/-) BALB/c mice lose muscle
      strength and muscle AChR to a greater extent than AChR-immunized WT mice. These
      observations demonstrate that IgG1 deficiency leads to increased severity of EAMG
      associated with an increase in complement activating IgG isotypes. Further
      studies are needed to dissect the specific role or mechanism of IgG1 in limiting
      EAMG and that of EAMG exacerbating role of complement activating IgG3 and IgG2a
      in IgG1 deficiency. 

PMID- 25867471
TI  - GAD65 epitope mapping and search for novel autoantibodies in GAD-associated
      neurological disorders.
AB  - Antibodies against Glutamic-acid-decarboxylase (GAD65) are seen in various CNS
      excitability disorders including stiff-person syndrome, cerebellar ataxia,
      encephalitis and epilepsy. To explore pathogenicity, we examined whether distinct
      epitope specificities or other co-existing antibodies may account for each
      disorder. The epitope recognized by all 27 tested patients, irrespective of
      clinical phenotype, corresponded to the catalytic core of GAD. No autoantibodies
      against known GABAergic antigens were found. In a screen for novel specificities
      using live hippocampal neurons, three epilepsy patients, but no other, were
      positive. We conclude that no GAD-specific epitope defines any neurological
      syndrome but other antibody specificities may account for certain phenotypes. 

PMID- 25867472
TI  - Effect of sepsis on behavioral changes on the ketamine-induced animal model of
      schizophrenia.
AB  - This study aimed to evaluate the effect of sepsis on behavioral changes on the
      ketamine-induced animal model of schizophrenia. Male Wistar rats underwent Cecal
      Ligation and Perporation (CLP) with "basic support" or were sham-operated. After
      30 days, the animals were submitted to a model of schizophrenia by injection of
      Ketamine. The behavior tests were performed after 30 min of the injection of
      Ketamine or saline. Ketamine in doses of 15 and 25mg/kg increased locomotor
      activity, latency to first contact in the social interaction and stereotyped
      behavior. Some changes caused by sepsis may be associated with a predisposition
      to develop schizophrenia in the animal model.

PMID- 25867474
TI  - Antimicrobial action of water-soluble beta-chitosan against clinical multi-drug
      resistant bacteria.
AB  - Recently, the number of patients infected by drug-resistant pathogenic microbes
      has increased remarkably worldwide, and a number of studies have reported new
      antibiotics from natural sources. Among them, chitosan, with a high molecular
      weight and alpha-conformation, exhibits potent antimicrobial activity, but useful
      applications as an antibiotic are limited by its cytotoxicity and insolubility at
      physiological pH. In the present study, the antibacterial activity of low
      molecular weight water-soluble (LMWS) alpha-chitosan (alpha1k, alpha5k, and
      alpha10k with molecular masses of 1, 5, and 10 kDa, respectively) and beta
      chitosan (beta1k, beta5k, and beta10k) was compared using a range of pathogenic
      bacteria containing drug-resistant bacteria isolated from patients at different
      pH. Interestingly, beta5k and beta10k exhibited potent antibacterial activity,
      even at pH 7.4, whereas only alpha10k was effective at pH 7.4. The active target
      of beta-chitosan is the bacterial membrane, where the leakage of calcein is
      induced in artificial PE/PG vesicles, bacterial mimetic membrane. Moreover,
      scanning electron microscopy showed that they caused significant morphological
      changes on the bacterial surfaces. An in vivo study utilizing a bacteria-infected
      mouse model found that LMWS beta-chitosan could be used as a candidate in anti
      infective or wound healing therapeutic applications. 

PMID- 25867473
TI  - TET1 is a tumor suppressor of hematopoietic malignancy.
AB  - The methylcytosine dioxygenase TET1 ('ten-eleven translocation 1') is an
      important regulator of 5-hydroxymethylcytosine (5hmC) in embryonic stem cells.
      The diminished expression of TET proteins and loss of 5hmC in many tumors
      suggests a critical role for the maintenance of this epigenetic modification.
      Here we found that deletion of Tet1 promoted the development of B cell lymphoma
      in mice. TET1 was required for maintenance of the normal abundance and
      distribution of 5hmC, which prevented hypermethylation of DNA, and for regulation
      of the B cell lineage and of genes encoding molecules involved in chromosome
      maintenance and DNA repair. Whole-exome sequencing of TET1-deficient tumors
      revealed mutations frequently found in non-Hodgkin B cell lymphoma (B-NHL), in
      which TET1 was hypermethylated and transcriptionally silenced. Our findings
      provide in vivo evidence of a function for TET1 as a tumor suppressor of
      hematopoietic malignancy. 

PMID- 25867475
TI  - Nitrogen removal from micro-polluted reservoir water by indigenous aerobic
      denitrifiers.
AB  - Treatment of micro-polluted source water is receiving increasing attention
      because of environmental awareness on a global level. We isolated and identified
      aerobic denitrifying bacteria Zoogloea sp. N299, Acinetobacter sp. G107, and
      Acinetobacter sp. 81Y and used these to remediate samples of their native source
      water. We first domesticated the isolated strains in the source water, and the 48
      h nitrate removal rates of strains N299, G107, and 81Y reached 33.69%, 28.28%,
      and 22.86%, respectively, with no nitrite accumulation. We then conducted a
      source-water remediation experiment and cultured the domesticated strains (each
      at a dry cell weight concentration of 0.4 ppm) together in a sample of source
      water at 20-26  degrees C and a dissolved oxygen concentration of 3-7 mg/L for 60
      days. The nitrate concentration of the system decreased from 1.57 +/- 0.02 to
      0.42 +/- 0.01 mg/L and that of a control system decreased from 1.63 +/- 0.02 to
      1.30 +/- 0.01 mg/L, each with no nitrite accumulation. Total nitrogen of the
      bacterial system changed from 2.31 +/- 0.12 to 1.09 +/- 0.01 mg/L, while that of
      the control system changed from 2.51 +/- 0.13 to 1.72 +/- 0.06 mg/L. The
      densities of aerobic denitrification bacteria in the experimental and control
      systems ranged from 2.8 * 10(4) to 2 * 10(7) cfu/mL and from 7.75 * 10(3) to 5.5
      * 10(5) cfu/mL, respectively. The permanganate index in the experimental and
      control systems decreased from 5.94 +/- 0.12 to 3.10 +/- 0.08 mg/L and from 6.02
      +/- 0.13 to 3.61 +/- 0.11 mg/L, respectively, over the course of the experiment.
      Next, we supplemented samples of the experimental and control systems with
      additional bacteria or additional source water and cultivated the systems for
      another 35 days. The additional bacteria did little to improve the water quality.
      The additional source water provided supplemental carbon and brought the nitrate
      removal rate in the experimental system to 16.97%, while that in the control
      system reached only 3.01%, with no nitrite accumulation in either system. Our
      results show that aerobic denitrifying bacteria remain highly active after
      domestication and demonstrate the applicability of such organisms in the
      bioremediation of oligotrophic ecosystems.

PMID- 25867476
TI  - Development of carbon nanotube modified cement paste with microencapsulated phase
      change material for structural-functional integrated application.
AB  - Microencapsulated phase-change materials (MPCM) can be used to develop a
      structural-functional integrated cement paste having high heat storage efficiency
      and suitable mechanical strength. However, the incorporation of MPCM has been
      found to degrade the mechanical properties of cement based composites. Therefore,
      in this research, the effect of carbon nanotubes (CNTs) on the properties of MPCM
      cement paste was evaluated. Test results showed that the incorporation of CNTs in
      MPCM cement paste accelerated the cement hydration reaction. SEM micrograph
      showed that CNTs were tightly attached to the cement hydration products. At the
      age of 28 days, the percentage increase in flexural and compressive strength with
      different dosage of CNTs was found to be up to 41% and 5% respectively. The
      optimum dosage of CNTs incorporated in MPCM cement paste was found to be 0.5 wt
      %. From the thermal performance test, it was found that the cement paste panels
      incorporated with different percentages of MPCM reduced the temperature measured
      at the center of the room by up to 4.6  degrees C. Inverse relationship was found
      between maximum temperature measured at the center of the room and the dosage of
      MPCM. 

PMID- 25867477
TI  - Heavy metal complexation of thiol-containing peptides from soy glycinin
      hydrolysates.
AB  - Many thiol-containing molecules show heavy metal complexation ability and are
      used as antidotes. In this study, the potential function associated with thiol
      containing peptides (TCPs) from soy protein hydrolysates as natural detoxicants
      for heavy metals is reported. TCPs enriched by Thiopropyl-Sepharose 6B covalent
      chromatography had different molecular weight distributions as well as different
      numbers of proton dissociable groups, depending on the proteases and degree of
      hydrolysis. The major contribution of sulfhydryl groups was confirmed by the
      largest pH decrease between 8.0 and 8.5 of the pH titration curves. The
      complexation of TCPs with heavy metals was evaluated by stability constants
      (betan) of TCP-metal complexes whose stoichiometry was found to be 1:1 (ML) and
      1:2 (ML2). TCPs from degree of hydrolysis of 25% hydrolysates gave high
      affinities towards Hg2+, Cd2+, and Pb2+ (giving similar or even bigger lgbeta
      values than that of glutathione). A significantly positive correlation was found
      between the logarithm of stability constants for ML2 (lgbeta2) and the sulfhydryl
      group content. Molecular weight distribution of TCPs affected the complexation
      with Pb2+ notably more than Hg2+ and Cd2+. These results suggest that soy TCPs
      have the potential to be used in the formulation of functional foods to
      counteract heavy metal accumulation in humans.

PMID- 25867478
TI  - Expression of the aryl hydrocarbon receptor in growth plate cartilage and the
      impact of its local modulation on longitudinal bone growth.
AB  - Although dioxin has been reported to impair bone growth in both humans and
      animals, the underlying mechanisms have not been clarified. We conducted this
      study to rule out if dioxin may directly target the growth plate, via local
      modulation of the aryl hydrocarbon receptor (AhR). Initial studies in rare tissue
      samples of the human growth plate confirmed that the AhR protein is widely
      expressed in growth plate cartilage. To explore the local role of the AhR,
      mechanistic studies were performed in a well-established model of cultured fetal
      rat metatarsal bones. The longitudinal growth of these bones was monitored while
      being exposed to AhR modulators. The AhR agonist, 2,3,7,8-tetrachlorodibenzo-p
      dioxin, did not affect bone growth at any concentrations tested (1 pM-10 nM). In
      contrast, the AhR antagonist, alpha-naphthoflavone, suppressed bone growth and
      increased chondrocyte apoptosis, although only at a high, potentially cytotoxic
      concentration (50 uM). We conclude that although the AhR is widely expressed in
      the growth plate, bone growth is not modulated when locally activated, and
      therefore, dioxin-induced growth failure is likely mediated through systemic
      rather than local actions. 

PMID- 25867479
TI  - Iron oxide nanoparticles for magnetically-guided and magnetically-responsive drug
      delivery.
AB  - In this review, we discuss the recent advances in and problems with the use of
      magnetically-guided and magnetically-responsive nanoparticles in drug delivery
      and magnetofection. In magnetically-guided nanoparticles, a constant external
      magnetic field is used to transport magnetic nanoparticles loaded with drugs to a
      specific site within the body or to increase the transfection capacity.
      Magnetofection is the delivery of nucleic acids under the influence of a magnetic
      field acting on nucleic acid vectors that are associated with magnetic
      nanoparticles. In magnetically-responsive nanoparticles, magnetic nanoparticles
      are encapsulated or embedded in a larger colloidal structure that carries a drug.
      In this last case, an alternating magnetic field can modify the structure of the
      colloid, thereby providing spatial and temporal control over drug release. 

PMID- 25867480
TI  - Anti-inflammatory effect of emodin via attenuation of NLRP3 inflammasome
      activation.
AB  - Emodin, an active constituent of oriental herbs, is widely used to treat allergy,
      inflammation, and other symptoms. This study provides the scientific basis for
      the anti-inflammasome effects of emodin on both in vitro and in vivo experimental
      models. Bone marrow-derived macrophages were used to study the effects of emodin
      on inflammasome activation by using inflammasome inducers such as ATP, nigericin,
      and silica crystals. The lipopolysaccharide (LPS)-induced endotoxin shock model
      was employed to study the effect of emodin on in vivo efficacy. Emodin treatment
      attenuated interleukin (IL)-1beta secretion via the inhibition of NOD-like
      receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation
      induced by ATP, nigericin, and silica crystals. Further, emodin ameliorated the
      severity of NLRP3 inflammasome-mediated symptoms in LPS-induced endotoxin mouse
      models. This study is the first to reveal mechanism-based evidence, especially
      with respect to regulation of inflammasome activation, substantiating traditional
      claims of emodin in the treatment of inflammation-related disorders. 

PMID- 25867481
TI  - Sequence features of Drosha and Dicer cleavage sites affect the complexity of
      isomiRs.
AB  - The deep-sequencing of small RNAs has revealed that different numbers and
      proportions of miRNA variants called isomiRs are formed from single miRNA genes
      and that this effect is attributable mainly to imprecise cleavage by Drosha and
      Dicer. Factors that influence the degree of cleavage precision of Drosha and
      Dicer are under investigation, and their identification may improve our
      understanding of the mechanisms by which cells modulate the regulatory potential
      of miRNAs. In this study, we focused on the sequences and structural determinants
      of Drosha and Dicer cleavage sites, which may explain the generation of
      homogeneous miRNAs (in which a single isomiR strongly predominates) as well as
      the generation of heterogeneous miRNAs. Using deep-sequencing data for small
      RNAs, we demonstrate that the generation of homogeneous miRNAs requires more
      sequence constraints at the cleavage sites than the formation of heterogeneous
      miRNAs. Additionally, our results indicate that specific Drosha cleavage sites
      have more sequence determinants in miRNA precursors than specific cleavage sites
      for Dicer and that secondary structural motifs in the miRNA precursors influence
      the precision of Dicer cleavage. Together, we present the sequence and structural
      features of Drosha and Dicer cleavage sites that influence the heterogeneity of
      the released miRNAs. 

PMID- 25867482
TI  - Chemical conversion pathways and kinetic modeling for the OH-initiated reaction
      of triclosan in gas-phase.
AB  - As a widely used antimicrobial additive in daily consumption, attention has been
      paid to the degradation and conversion of triclosan for a long time. The quantum
      chemistry calculation and the canonical variational transition state theory are
      employed to investigate the mechanism and kinetic property. Besides addition and
      abstraction, oxidation pathways and further conversion pathways are also
      considered. The OH radicals could degrade triclosan to phenols, aldehydes, and
      other easily degradable substances. The conversion mechanisms of triclosan to the
      polychlorinated dibenzopdioxin and furan (PCDD/Fs) and polychlorinated biphenyls
      (PCBs) are clearly illustrated and the toxicity would be strengthened in such
      pathways. Single radical and diradical pathways are compared to study the
      conversion mechanism of dichlorodibenzo dioxin (DCDD). Furthermore,
      thermochemistry is discussed in detail. Kinetic property is calculated and the
      consequent ratio of k add/k total and k abs/k total at 298.15 K are 0.955 and
      0.045, respectively. Thus, the OH radical addition reactions are predominant, the
      substitute position of OH radical on triclosan is very important to generate PCDD
      and furan, and biradical is also a vital intermediate to produce dioxin.

PMID- 25867483
TI  - Home Improvement in HIV Primary Care: Investigating the Patient-Centered Medical
      Home Model for People Living with HIV/AIDS.
AB  - This article details the processes and findings of a 3-year demonstration project
      implementing population health management and the Patient-Centered Medical Home
      (PCMH) model in 3 community health centers in Alameda County, California. The
      article provides a first look at the PCMH Continuum, a tool for aiding staff in
      conceptualizing and implementing complex organizational change. Findings of the
      project evaluation also are shared, comprising a road map for other organizations
      looking to implement population health management, panel management, and PCMH.
      The article reflects on lessons learned and best practices from the demonstration
      project.

PMID- 25867484
TI  - NMDA receptor activation upstream of methyl farnesoate signaling for short day
      induced male offspring production in the water flea, Daphnia pulex.
AB  - BACKGROUND: The cladoceran crustacean Daphnia pulex produces female offspring by
      parthenogenesis under favorable conditions, but in response to various
      unfavorable external stimuli, it produces male offspring (environmental sex
      determination: ESD). We recently established an innovative system for ESD studies
      using D. pulex WTN6 strain, in which the sex of the offspring can be controlled
      simply by changes in the photoperiod: the long-day and short-day conditions can
      induce female and male offspring, respectively. Taking advantage of this system,
      we demonstrated that de novo methyl farnesoate (MF) synthesis is necessary for
      male offspring production. These results indicate the key role of innate MF
      signaling as a conductor between external environmental stimuli and the
      endogenous male developmental pathway. Despite these findings, the molecular
      mechanisms underlying up- and downstream signaling of MF have not yet been well
      elucidated in D. pulex. RESULTS: To elucidate up- and downstream events of MF
      signaling during sex determination processes, we compared the transcriptomes of
      daphnids reared under the long-day (female) condition with short-day (male) and
      MF-treated (male) conditions. We found that genes involved in ionotropic
      glutamate receptors, known to mediate the vast majority of excitatory
      neurotransmitting processes in various organisms, were significantly activated in
      daphnids by the short-day condition but not by MF treatment. Administration of
      specific agonists and antagonists, especially for the N-methyl-D-aspartic acid
      (NMDA) receptor, strongly increased or decreased, respectively, the proportion of
      male-producing mothers. Moreover, we also identified genes responsible for male
      production (e.g., protein kinase C pathway-related genes). Such genes were
      generally shared between the short-day reared and MF-treated daphnids.
      CONCLUSIONS: We identified several candidate genes regulating ESD which strongly
      suggests that these genes may be essential factors for male offspring production
      as an upstream regulator of MF signaling in D. pulex. This study provides new
      insight into the fundamental mechanisms underlying how living organisms alter
      their phenotypes in response to various external environments.

PMID- 25867486
TI  - Item diagnostics in multivariate discrete data.
AB  - Researchers who evaluate the fit of psychometric models to binary or multinomial
      items often look at univariate and bivariate residuals to determine how a poorly
      fitting model can be improved. There is a class of z statistics and also a class
      of generalized X2 statistics that can be used for examining these marginal fits.
      We describe these statistics and compare them with regard to the control of Type
      I error and statistical power. We show how the class of z statistics can be
      extended to accommodate items with multinomial response options. We provide
      guidelines for the use of these statistics, including how to control for multiple
      testing, and present 2 detailed examples. Using the root mean square error of
      approximation (RMSEA) for discrete data to adjudge fit, the examples illustrate
      how the use of these methods can dramatically improve the fit of item response
      theory models to widely used measures in personality and clinical psychology.

PMID- 25867485
TI  - Sedimentation equilibrium of a small oligomer-forming membrane protein: effect of
      histidine protonation on pentameric stability.
AB  - Analytical ultracentrifugation (AUC) can be used to study reversible interactions
      between macromolecules over a wide range of interaction strengths and under
      physiological conditions. This makes AUC a method of choice to quantitatively
      assess stoichiometry and thermodynamics of homo- and hetero-association that are
      transient and reversible in biochemical processes. In the modality of
      sedimentation equilibrium (SE), a balance between diffusion and sedimentation
      provides a profile as a function of radial distance that depends on a specific
      association model. Herein, a detailed SE protocol is described to determine the
      size and monomer-monomer association energy of a small membrane protein oligomer
      using an analytical ultracentrifuge. AUC-ES is label-free, only based on physical
      principles, and can be used on both water soluble and membrane proteins. An
      example is shown of the latter, the small hydrophobic (SH) protein in the human
      respiratory syncytial virus (hRSV), a 65-amino acid polypeptide with a single
      alpha-helical transmembrane (TM) domain that forms pentameric ion channels. NMR
      based structural data shows that SH protein has two protonatable His residues in
      its transmembrane domain that are oriented facing the lumen of the channel. SE
      experiments have been designed to determine how pH affects association constant
      and the oligomeric size of SH protein. While the pentameric form was preserved in
      all cases, its association constant was reduced at low pH. These data are in
      agreement with a similar pH dependency observed for SH channel activity,
      consistent with a lumenal orientation of the two His residues in SH protein. The
      latter may experience electrostatic repulsion and reduced oligomer stability at
      low pH. In summary, this method is applicable whenever quantitative information
      on subtle protein-protein association changes in physiological conditions have to
      be measured. 

PMID- 25867487
TI  - Fitting a linear-linear piecewise growth mixture model with unknown knots: A
      comparison of two common approaches to inference.
AB  - A linear-linear piecewise growth mixture model (PGMM) is appropriate for
      analyzing segmented (disjointed) change in individual behavior over time, where
      the data come from a mixture of 2 or more latent classes, and the underlying
      growth trajectories in the different segments of the developmental process within
      each latent class are linear. A PGMM allows the knot (change point), the time of
      transition from 1 phase (segment) to another, to be estimated (when it is not
      known a priori) along with the other model parameters. To assist researchers in
      deciding which estimation method is most advantageous for analyzing this kind of
      mixture data, the current research compares 2 popular approaches to inference for
      PGMMs: maximum likelihood (ML) via an expectation-maximization (EM) algorithm,
      and Markov chain Monte Carlo (MCMC) for Bayesian inference. Monte Carlo
      simulations were carried out to investigate and compare the ability of the 2
      approaches to recover the true parameters in linear-linear PGMMs with unknown
      knots. The results show that MCMC for Bayesian inference outperformed ML via EM
      in nearly every simulation scenario. Real data examples are also presented, and
      the corresponding computer codes for model fitting are provided in the Appendix
      to aid practitioners who wish to apply this class of models.

PMID- 25867488
TI  - Indigenous peoples and human rights: some considerations for the occupational
      therapy profession in Australia.

PMID- 25867489
TI  - Strong Enhancement of Second Harmonic Emission by Plasmonic Resonances at the
      Second Harmonic Wavelength.
AB  - We perform second harmonic spectroscopy of aluminum nanoantenna arrays that
      exhibit plasmonic resonances at the second harmonic wavelength between 450 and
      570 nm by focusing sub-30 fs laser pulses tunable from 900 to 1140 nm onto the
      nanoantenna arrays. We find that a plasmonic resonance at the second harmonic
      wavelength boosts the overall nonlinear process by more than an order of
      magnitude. In particular, in the measurement the resonant second harmonic
      polarization component is a factor of about 70 stronger when compared to the
      perpendicular off-resonant second harmonic polarization. Furthermore, the maximum
      of the second harmonic conversion efficiency is found to be slightly blue-shifted
      with respect to the peak of the linear optical far-field spectrum. This fact can
      be understood from a simple model that accounts for the almost off-resonant
      absorption at the fundamental wavelength and the resonant emission process at the
      second harmonic. 

PMID- 25867490
TI  - Hysterectomies in Finland in 1990-2012: comparison of outcomes between trainees
      and specialists.
AB  - OBJECTIVE: To assess trends for hysterectomy methods in the Nordic countries and
      to compare outcomes of hysterectomies in Finland done by trainees with those done
      by specialists. DESIGN: Register-based study. SETTING: NOMESCO database for the
      Nordic countries and the Finnish Hospital Discharge Register. POPULATION:
      National prospective cohort of 5279 hysterectomies in Finland. METHODS: Numbers
      of hysterectomies in the Nordic countries were collected in 1995-2011 and in
      Finland in 1990-2012. The Finhyst study to collect data on hysterectomies for
      benign indications was carried out in Finland in 2006. Information concerning
      patients, surgeons, and hysterectomy outcome was analysed. MAIN OUTCOME MEASURES:
      Hysterectomy numbers and methods. Operating time, blood loss, and complications
      in hysterectomies done by trainees and specialists. RESULTS: In Finland, the rate
      of hysterectomies has been reduced by approximately 50% since the 1990s and is
      now similar to that in the other Nordic countries. The laparoscopic method is
      twice as common in Finland as in other Nordic countries, constituting 35-40% of
      all hysterectomies. The operating time for all hysterectomy methods was 16-25%
      longer among trainees than specialists. For the abdominal or laparoscopic methods
      there were no significant differences in the complication rates between the
      groups. In the vaginal approach, blood loss of >=1000 mL was slightly more common
      in operations done by trainees (1.3% vs. 2.6%, p = 0.037). CONCLUSIONS:
      Laparoscopic hysterectomy is more common in Finland than in the other Nordic
      countries. Although trainees need more time to operate, there were no differences
      between the trainees and the specialists with regard to major complication rates.

PMID- 25867491
TI  - Biolistic transformation of a fluorescent tagged gene into the opportunistic
      fungal pathogen Cryptococcus neoformans.
AB  - The basidiomycete Cryptococcus neoformans, an invasive opportunistic pathogen of
      the central nervous system, is the most frequent cause of fungal meningitis
      worldwide resulting in more than 625,000 deaths per year worldwide. Although
      electroporation has been developed for the transformation of plasmids in
      Cryptococcus, only biolistic delivery provides an effective means to transform
      linear DNA that can be integrated into the genome by homologous recombination. 
      Acetate has been shown to be a major fermentation product during cryptococcal
      infection, but the significance of this is not yet known. A bacterial pathway
      composed of the enzymes xylulose-5-phosphate/fructose-6-phosphate phosphoketolase
      (Xfp) and acetate kinase (Ack) is one of three potential pathways for acetate
      production in C. neoformans. Here, we demonstrate the biolistic transformation of
      a construct, which has the gene encoding Ack fused to the fluorescent tag
      mCherry, into C. neoformans. We then confirm integration of the ACK-mCherry
      fusion into the ACK locus. 

PMID- 25867492
TI  - A pilot study of maudsley family therapy with group dialectical behavior therapy
      skills training in an intensive outpatient program for adolescent eating
      disorders.
AB  - OBJECTIVE: The goal of this study was to provide pilot clinical data on the
      effectiveness of an intensive outpatient treatment model for adolescent eating
      disorders that combines Maudsley-based family therapy and group dialectical
      behavior therapy skills training. METHOD: Measures of physical and psychological
      status were gathered upon admission, discharge, and at 3 follow-up intervals.
      RESULTS: Adolescents who completed the program gained a significant amount of
      weight and experienced a significant decrease in eating disorder psychopathology.
      At the 1-year follow-up, 64% of adolescents were weight restored and menstruating
      normally. Measures of eating disorder psychopathology continued to improve up to
      a year after treatment. CONCLUSIONS: This pilot, multimodal program warrants
      further investigation and may be an effective intermediate level of care
      treatment option for adolescent eating disorders.

PMID- 25867493
TI  - Barriers and Incentives to Rural Health Department Accreditation.
AB  - CONTEXT: Accreditation of local health departments has been identified as a
      crucial strategy for strengthening the public health infrastructure. Rural local
      health departments (RLHDs) face many challenges including lower levels of
      staffing and funding than local health departments serving metropolitan or urban
      areas; simultaneously their populations experience health disparities related to
      risky health behaviors, health outcomes, and access to medical care. Through
      accreditation, rural local health departments can become better equipped to meet
      the needs of their communities. OBJECTIVE: To better understand the needs of
      communities by assessing barriers and incentives to state-level accreditation in
      Missouri from the RLHD perspective. DESIGN: Qualitative analysis of
      semistructured key informant interviews with Missouri local health departments
      serving rural communities. PARTICIPANTS: Eleven administrators of RLHDs, 7 from
      accredited and 4 from unaccredited departments, were interviewed. Population size
      served ranged from 6400 to 52,000 for accredited RLHDs and from 7200 to 73,000
      for unaccredited RLHDs. RESULTS: Unaccredited RLHDs identified more barriers to
      accreditation than accredited RLHDs. Time was a major barrier to seeking
      accreditation. Unaccredited RLHDs overall did not see accreditation as a priority
      for their agency and failed to the see value of accreditation. Accredited RLHDs
      listed more incentives than their unaccredited counterparts. Unaccredited RLHDs
      identified accountability, becoming more effective and efficient, staff
      development, and eventual funding as incentives to accreditation. CONCLUSIONS:
      There is a need for better documentation of measurable benefits in order for an
      RLHD to pursue voluntary accreditation. Those who pursue accreditation are likely
      to see benefits after the fact, but those who do not pursue do not see the
      immediate and direct benefits of voluntary accreditation. The finding from this
      study of state-level accreditation in Missouri provides insight that can be
      translated to national accreditation.

PMID- 25867494
TI  - Supporting Medical Home Transformation Through Evaluation of Patient Experience
      in a Large Culturally Diverse Primary Care Safety Net.
AB  - CONTEXT: The prevalence of chronic disease in the United States is rapidly
      increasing, with a disproportionate number of underserved, vulnerable patients
      sharing the burden. The Patient-Centered Medical Home (PCMH) is a care delivery
      model that has shown promise to improve primary care and address the burden of
      chronic illness. OBJECTIVE: The purpose of this study was to (1) understand
      patient characteristics that might influence perceived patient experience in a
      large primary care safety net undergoing PCMH transformation; (2) identify
      community-level quality improvement opportunities to support ongoing
      transformation activities; and (3) establish a baseline of patient experience
      across the primary care safety net that could be used in repeated evaluations
      over the course of transformation. DESIGN: A cross-sectional study design was
      used to conduct this research. SETTING AND PARTICIPANTS: A total of 351 racially
      and ethnically diverse patients of 4 primary care safety net organizations in
      Broward County, Florida, were surveyed regarding their experience with access to
      care and coordination of care. MAIN OUTCOME MEASURE: Reported access to care and
      coordination of care. RESULTS: Patients with chronic disease who reported having
      visited the clinic 3 or more times in the past 12 months reported a better
      coordination of care experience than patients who had fewer than 3 visits in the
      past 12 months (odds ratio = 3.57; 95% confidence interval, 1.76-7.24). Patients
      without chronic disease who had been receiving care at the clinic for 2 or more
      years of care reported worse experience with access to care than patients with
      less than 2 years of care (odds ratio = 0.26; 95% confidence interval, 0.11
      0.60.) Race, ethnicity, language, and education were not significant predictors
      of patient experience. CONCLUSION: Findings support ongoing efforts to improve
      patient engagement among all patients and to enhance resources to manage chronic
      disease, including community-based self-management programs, in primary care
      safety nets undergoing PCMH transformation.

PMID- 25867495
TI  - Contact Investigations Around Mycobacterium tuberculosis Patients Without
      Positive Respiratory Culture.
AB  - OBJECTIVE: To evaluate the yield and effectiveness of contact investigations
      conducted around potentially infectious tuberculosis (TB) patients with no
      positive respiratory culture for Mycobacterium tuberculosis in New York City
      (NYC). DESIGN: All TB patients without a positive respiratory culture from 2003
      to 2012 were extracted from the NYC TB registry, and all patients eligible for
      contact investigation and their contacts were evaluated. Patients without a
      positive respiratory culture were defined as eligible for contact investigation
      if they had a respiratory nucleic acid amplification result positive for M
      tuberculosis, a cavitary chest radiograph, or a positive respiratory acid-fast
      bacilli smear. SETTING: NYC, New York. MAIN OUTCOME MEASURES: To evaluate the
      yield of the investigations, the number of contacts identified and the outcome of
      testing was quantified. Potential transmission was defined on the basis of
      whether active TB patients were detected among the contacts and if a contact had
      a TB test conversion. RESULTS: From 2003 to 2012, there were 2191 TB patients
      without a positive respiratory culture in NYC, 374 (17%) of which were considered
      eligible for contact investigation. A total of 11 096 contacts were identified
      around 300 (80%) eligible patients, 136 of whom had a diagnosis of TB infection;
      of those with TB infection who initiated preventive treatment, 66% completed
      treatment. Potential transmission was identified around 14 patients, with the
      identification of 2 additional cases of active TB and 15 contacts with TB
      infection test conversion. CONCLUSIONS: Conducting contact investigations around
      patients without a positive respiratory culture yielded evidence of possible
      transmission and led to the identification and treatment of new TB cases and
      those with TB infection. These findings suggest that these investigations should
      be conducted in settings where resources permit.

PMID- 25867496
TI  - Local Health Departments' Approaches to Deal With Recession: What Strategies Are
      Used to Minimize the Negative Impact on Public Health Services to Community?
AB  - CONTEXT: Local health departments (LHDs) are crucial components in the public
      health system. As with their state counterparts, operating since the 2008
      recession has proven financially difficult for the majority of the nation's 2800
      LHDs. These health departments have elected to employ a variety of strategies to
      maintain operations and public-facing services and programs. OBJECTIVES: This
      study aimed to assess strategies used by LHDs to minimize the negative impact on
      services to community and to examine variation in these strategies by the size of
      population in LHD jurisdiction. DESIGN AND PARTICIPANTS: The design of this
      research brief report is observational, based on cross-sectional data from a
      nationally representative sample of 957 LHDs that enumerates and characterizes
      the nature of their responses to austerity. OUTCOMES MEASURES: The main outcome
      measures included 19 strategies. We used descriptive and bivariate analyses to
      highlight our study findings. RESULTS: LHDs use a variety of strategies to
      mitigate negative impacts on the public health services in their communities,
      focusing on workforce, funding, service referral, and several other areas. The
      most frequently used strategies include cross-training staff, increasing work
      hours, pursuing new funding, resource sharing, and seeking fees for services
      provided. Some minor variation by the size of jurisdiction population existed in
      frequency of top 10 strategies used by LHDs. CONCLUSIONS: Some of the LHD
      strategies to deal with the impact of recession address immediate issues caused
      by budget cuts and might be short-term fixes, including increasing workload of
      employees, and pay freezes. Other strategies, such as seeking new sources of
      revenues and resource sharing, can have potentially positive effects in the long
      run.

PMID- 25867497
TI  - Swine Dialyzable Spleen Extract as Antiviral Prophylaxis.
AB  - Worldwide, the most highly consumed meat is of porcine origin. The production and
      distribution of swine meat are affected by diverse health matters, such as
      influenza and diarrhea, which cause head losses and require the use of
      antibiotics and other drugs in hog farms. To stimulate newborn piglet immune
      responses and increase resistance to infections, we developed a spray-drying
      technique to produce dried swine dialyzable spleen extract (sDSE), an
      immunomodulator. Based on the size-exclusion ultra performance liquid
      chromatography quantitative analysis, it was possible to recover up to 58% of the
      product after the drying process. The biological activity of orally administered
      dried sDSE increased mouse survival and induced cytokine production in a herpes
      infection model. 

PMID- 25867498
TI  - Influence of gastrointestinal factors on glucose metabolism in patients with
      cirrhosis.
AB  - BACKGROUND AND AIM: The impaired glucose tolerance in cirrhosis is poorly
      understood. We evaluated the influence of gastrointestinal-mediated glucose
      disposal and incretin effect in patients with cirrhosis. METHODS: Non-diabetic
      patients with Child-Pugh A or B cirrhosis (n = 10) and matched healthy controls
      (n = 10) underwent a 50-g oral glucose tolerance test (OGTT) and an isoglycemic
      intravenous glucose infusion. We presented data as median +/- interquartile range
      and compared groups using non-parametric analysis of variance. RESULTS: Patients
      with cirrhosis were glucose intolerant compared with healthy controls (4-h
      OGTTAUC : 609 +/- 458 vs 180 +/- 155 min * mmol/L; P = 0.005), insulin resistant
      (homeostatic model assessment for insulin resistance: 3.7 +/- 4.9 vs 2.6 +/- 1.4;
      P = 0.014) and had fasting hyperglucagonemia (8 +/- 3 vs 3 +/- 4 pmol/L; P =
      0.027). Isoglycemia was achieved using 35 +/- 12 g of intravenous glucose in
      patients with cirrhosis compared with 24 +/- 10 g in healthy controls (P =
      0.003). The gastrointestinal-mediated glucose disposal was markedly lower in
      patients with cirrhosis (30 +/- 23 vs 52 +/- 20%; P = 0.003). Despite higher
      levels of the incretin hormones glucagon-like peptide-1 and glucose-dependent
      insulinotropic peptide patients with cirrhosis had reduced incretin effect (35 +/
      44 vs 55 +/- 30%; P = 0.008). CONCLUSION: Impaired gastrointestinal-mediated
      glucose disposal and reduced incretin effect may contribute to the glucose
      intolerance seen in patients with cirrhosis.

PMID- 25867499
TI  - The Lake Wobegon Effect: Why Most Patients Are at Below-Average Risk.

PMID- 25867500
TI  - Differential scanning fluorimetry for monitoring RNA stability.
AB  - Cellular RNA function is closely linked to RNA structure. It is therefore
      imperative to develop methods that report on structural stability of RNA and how
      it is modulated by binding of ions, other osmolytes, and RNA-binding ligands.
      Here, we present a novel method to analyze the stability of virtually any
      structured RNA in a highly parallel fashion. This method can easily determine the
      influence of various additives on RNA stability, and even characterize ligand
      induced stabilization of riboswitch RNA. Current approaches to assess RNA
      stability include thermal melting profiles (absorption or circular dichroism) and
      differential scanning calorimetry. These techniques, however, require a
      substantial amount of material and cannot be significantly parallelized. Current
      fluorescence spectroscopic methods rely on intercalating dyes, which alter the
      stability of RNA. We employ the commercial fluorescent dye RiboGreen, which
      discriminates between single-stranded (or unstructured regions) and double
      stranded RNA. Binding leads to an increase in fluorescence quantum yield, and
      thus reports structural changes by a change in fluorescence intensity. 

PMID- 25867501
TI  - Age-specific differences of dual n-back training.
AB  - Age-related decline in executive functions can be decisive in performing everyday
      tasks autonomously. Working memory (WM) is closely related to executive
      functions, and training of WM has yielded evidence toward cognitive plasticity in
      older adults. The training effects often transfer to untrained tasks and
      functions. These effects have mostly been shown in processes such as WM and
      attention, whereas studies investigating transfer to executive functions have
      been scarce. We trained older adults aged 57-73 years in a WM training task that
      was reported to be effective in producing transfer in young adults. The training
      intervention consisted of a dual n-back task including independently processed
      auditory and visual n-back tasks. We investigated transfer to tasks engaging
      executive functions, and compared the effects in older adults to those reported
      in young adults. We found that both training groups improved in the training
      task. Although the training effect in older adults was smaller than the training
      effect in young adults, the older adults still showed a notable improvement so
      that after training they performed on the same level as young adults without
      training. The older adults also showed transfer to an untrained WM updating task,
      a result that was in accordance with the findings in young adults; other transfer
      effects in older adults were lacking. We conclude that although transfer effects
      were scarce, the present study provides encouraging evidence toward the
      possibilities to compensate for age-related decline in executive functions by a
      WM training intervention.

PMID- 25867502
TI  - Supraliminal but not subliminal distracters bias working memory recall.
AB  - Information of which observers are not consciously aware can nevertheless
      influence perceptual processes. Whether subliminal information might exert an
      influence on working memory (WM) representations is less clear, and relatively
      few studies have examined the interactions between subliminal and supraliminal
      information in WM. We present 3 experiments examining this issue. Experiments 1a
      and b replicated the finding that orientation stimuli can influence behavior
      subliminally in a visuomotor priming task. Experiments 2 and 3 used the same
      orientation stimuli, but participants had to remember a target orientation and
      report it back by adjusting a probe orientation after a memory delay. Before or
      after presentation of the target orientation, a subliminal or supraliminal
      distracter orientation was presented that was either irrelevant for task
      completion and never had to be reported (Experiment 2), or was relevant for task
      completion because it had to be reported on some trials (Experiment 3). In both
      experiments, presentation of a supraliminal distracter influenced WM recall of
      the target orientation. When the distracter was presented subliminally, however,
      there was no bias in orientation recall. These results suggest that information
      stored in WM is protected from influences of subliminal stimuli, while online
      information processing is modulated by subliminal information.

PMID- 25867503
TI  - Spatial parameters at the basis of social transfer of learning.
AB  - Recent research indicates that practicing on a joint spatial compatibility task
      with an incompatible stimulus-response mapping affects subsequent joint Simon
      task performance, eliminating the social Simon effect. It has been well
      established that in individual contexts, for transfer of learning to occur,
      participants need to practice an incompatible association between stimulus and
      response positions. The mechanisms underlying transfer of learning in joint task
      performance are, however, less well understood. The present study was aimed at
      assessing the relative contribution of 3 different spatial relations
      characterizing the joint practice context: stimulus-response, stimulus
      participant, and participant-response relations. In 3 experiments, the authors
      manipulated the stimulus-response, stimulus-participant, and response-participant
      associations. We found that learning from the practice task did not transfer to
      the subsequent task when during practice stimulus-response associations were
      spatially incompatible and stimulus-participant associations were compatible
      (Experiment 1). However, a transfer of learning was evident when stimulus
      participant associations were spatially incompatible. This occurred both when
      response-participant associations were incompatible (Experiment 2) and when they
      were compatible (Experiment 3). These results seem to support an agent
      corepresentation account of correspondence effects emerging in joint settings
      since they suggest that, in social contexts, critical to obtain transfer-of
      learning effects is the spatial relation between stimulus and participant
      positions while the spatial relation between stimulus and response positions is
      irrelevant.

PMID- 25867504
TI  - Exemplar variance supports robust learning of facial identity.
AB  - Differences in the visual processing of familiar and unfamiliar faces have
      prompted considerable interest in face learning, the process by which unfamiliar
      faces become familiar. Previous work indicates that face learning is determined
      in part by exposure duration; unsurprisingly, viewing faces for longer affords
      superior performance on subsequent recognition tests. However, there has been
      further speculation that exemplar variation, experience of different exemplars of
      the same facial identity, contributes to face learning independently of viewing
      time. Several leading accounts of face learning, including the averaging and
      pictorial coding models, predict an exemplar variation advantage. Nevertheless,
      the exemplar variation hypothesis currently lacks empirical support. The present
      study therefore sought to test this prediction by comparing the effects of unique
      exemplar face learning--a condition rich in exemplar variation--and repeated
      exemplar face learning--a condition that equates viewing time, but constrains
      exemplar variation. Crucially, observers who received unique exemplar learning
      displayed better recognition of novel exemplars of the learned identities at
      test, than observers in the repeated exemplar condition. These results have
      important theoretical and substantive implications for models of face learning
      and for approaches to face training in applied contexts.

PMID- 25867506
TI  - The distracting impact of repeated visible and invisible onsets on focused
      attention.
AB  - A sudden peripheral onset is a powerful attentional attractor. However, in real
      life potentially distracting events do not always occur as a single event, but
      rather they can occur in a repetitive fashion. Hence, one of the aims of the
      present study was to investigate how the attentional system reacts to multiple
      consecutive onsets within the same trial. The results, quite surprisingly, showed
      that repeated peripheral onsets do not have a negative impact on visual
      performance, while they confirmed that a single peripheral onset captures focused
      attention. We hypothesize the existence of a short-term habituation mechanism
      that prevents visual attention from being continuously distracted by the same
      task-irrelevant event when this is rapidly repeated. A further aim of the study
      was to test the proposal according to which subliminal visual transients can
      bypass the conscious inhibitory control, thus resulting more distracting than
      supraliminal transients. We did not find in any of the 8 experiments that we
      conducted that subliminal onsets, either single or repeated, can grab attention
      when fully focused at fixation. Hence, in the case of sudden onsets, the general
      claim that task-irrelevant invisible stimuli can be more disturbing than visible
      ones does not seem to be fully justified.

PMID- 25867507
TI  - Differential effect of visual masking in perceptual categorization.
AB  - This article explores the visual information used to categorize stimuli drawn
      from a common stimulus space into verbal and nonverbal categories using 2
      experiments. Experiment 1 explores the effect of target duration on verbal and
      nonverbal categorization using backward masking to interrupt visual processing.
      With categories equated for difficulty for long and short target durations,
      intermediate target duration shows an advantage for verbal categorization over
      nonverbal categorization. Experiment 2 tests whether the results of Experiment 1
      can be explained by shorter target duration resulting in a smaller signal-to
      noise ratio of the categorization stimulus. To test for this possibility,
      Experiment 2 used integration masking with the same stimuli, categories, and
      masks as Experiment 1 with a varying level of mask opacity. As predicted, low
      mask opacity yielded similar results to long target duration while high mask
      opacity yielded similar results to short target duration. Importantly,
      intermediate mask opacity produced an advantage for verbal categorization over
      nonverbal categorization, similar to intermediate target duration. These results
      suggest that verbal and nonverbal categorization are affected differently by
      manipulations affecting the signal-to-noise ratio of the stimulus, consistent
      with multiple-system theories of categorizations. The results further suggest
      that verbal categorization may be more digital (and more robust to low signal-to
      noise ratio) while the information used in nonverbal categorization may be more
      analog (and less robust to lower signal-to-noise ratio). This article concludes
      with a discussion of how these new results affect the use of masking in
      perceptual categorization and multiple-system theories of perceptual category
      learning.

PMID- 25867508
TI  - Autonomic arousal and attentional orienting to visual threat are predicted by
      awareness.
AB  - The rapid detection and evaluation of threat is of fundamental importance for
      survival. Theories suggest that this evolutionary pressure has driven functional
      adaptations in a specialized visual pathway that evaluates threat independently
      of conscious awareness. This is supported by evidence that threat-relevant
      stimuli rendered invisible by backward masking can induce physiological fear
      responses and modulate spatial attention. The validity of these findings has
      since been questioned by research using stringent, objective measures of
      awareness. Here, we use a modified continuous flash suppression paradigm to ask
      whether threatening images induce adaptive changes in autonomic arousal,
      attention, or perception when presented outside of awareness. In trials where
      stimuli broke suppression to become visible, threatening stimuli induced a
      significantly larger skin conductance response than nonthreatening stimuli and
      attracted spatial attention over scrambled images. However, these effects were
      eliminated in trials where observers were unaware of the stimuli. In addition,
      concurrent behavioral data provided no evidence that threatening images gained
      prioritized access to awareness. Taken together, our data suggest that the
      evaluation and spatial detection of visual threat are predicted by awareness.

PMID- 25867509
TI  - Processing differences across regular and irregular inflections revealed through
      ERPs.
AB  - Research strongly suggests that printed words are recognized in terms of their
      constituent morphemes, but researchers have tended to consider the recognition of
      derivations and inflections in separate theoretical debates. Recently, Crepaldi
      et al. (2010) proposed a theory that claims to account for the recognition of
      both derivations and inflections. We investigated brain potentials in the context
      of masked priming to test 2 key predictions of this theory: (a) that regular
      inflections should prime their stems to a greater degree than irregular
      inflections should prime their stems and (b) that priming for regular inflections
      should arise earlier in the recognition process than priming for irregular
      inflections. Significant masked priming effects were observed for both regular
      and irregular inflections, though these effects were greater for regular
      inflections. ERP data further suggested that masked priming effects for regular
      and irregular inflections had different time courses. Priming for regular but not
      irregular inflections emerged in a time window reflecting processing up to 250 ms
      post target onset, and although priming for regular and irregular inflections was
      observed in a time window reflecting processing 400 to 600 ms post target onset,
      these effects arose earlier and were of greater magnitude for the regular
      inflections. These findings support a form-then-meaning characterization of the
      visual word processing system such as that proposed by Crepaldi et al. (2010) and
      raise challenges for alternative approaches.

PMID- 25867505
TI  - A relational structure of voluntary visual-attention abilities.
AB  - Many studies have examined attention mechanisms involved in specific behavioral
      tasks (e.g., search, tracking, distractor inhibition). However, relatively little
      is known about the relationships among those attention mechanisms. Is there a
      fundamental attention faculty that makes a person superior or inferior at most
      types of attention tasks, or do relatively independent processes mediate
      different attention skills? We focused on individual differences in voluntary
      visual-attention abilities using a battery of 11 representative tasks. An
      application of parallel analysis, hierarchical-cluster analysis, and
      multidimensional scaling to the intertask correlation matrix revealed 4
      functional clusters, representing spatiotemporal attention, global attention,
      transient attention, and sustained attention, organized along 2 dimensions, one
      contrasting spatiotemporal and global attention and the other contrasting
      transient and sustained attention. Comparison with the neuroscience literature
      suggests that the spatiotemporal-global dimension corresponds to the dorsal
      frontoparietal circuit and the transient-sustained dimension corresponds to the
      ventral frontoparietal circuit, with distinct subregions mediating the separate
      clusters within each dimension. We also obtained highly specific patterns of
      gender difference and of deficits for college students with elevated attention
      deficit/hyperactivity disorder traits. These group differences suggest that
      different mechanisms of voluntary visual attention can be selectively
      strengthened or weakened based on genetic, experiential, and/or pathological
      factors.

PMID- 25867510
TI  - Spatial scale, rather than nature of task or locomotion, modulates the spatial
      reference frame of attention.
AB  - Visuospatial attention is strongly biased to locations that had frequently
      contained a search target before. However, the function of this bias depends on
      the reference frame in which attended locations are coded. Previous research has
      shown a striking difference between tasks administered on a computer monitor and
      those administered in a large environment, with the former inducing viewer
      centered learning and the latter environment-centered learning. Why does
      environment-centered learning fail on a computer? Here, we tested 3
      possibilities: differences in spatial scale, the nature of task, and locomotion
      may each influence the reference frame of attention. Participants searched for a
      target on a monitor placed flat on a stand. On each trial, they stood at a
      different location around the monitor. The target was frequently located in a
      fixed area of the monitor, but changes in participants' perspective rendered this
      area random relative to the participants. Under incidental learning conditions,
      participants failed to acquire environment-centered learning even when (a) the
      task and display resembled those of a large-scale task and (b) the search task
      required locomotion. The difficulty in inducing environment-centered learning on
      a computer underscores the egocentric nature of visual attention. It supports the
      idea that spatial scale modulates the reference frame of attention.

PMID- 25867511
TI  - The selection and usage of information for perceiving and remembering intended
      and unintended object properties.
AB  - The current study was designed to investigate the linkage between intention,
      attention, and information selection and detection. Two experiments determined
      whether the intention to perceive maximum overhead reaching height with the use
      of handheld rods with different rotational inertia resulted in the ability to
      remember the rods' heaviness after they were removed from view. Participants were
      partially successful at distinguishing the heaviness of rods but only when visual
      information was restricted and reaching height was perceived using the rods by
      dynamic touch. The results support an ecological approach to attention, and
      suggest that information picked up for perception can support the memory of other
      properties of the environment if their informational bases are related.

PMID- 25867512
TI  - Speed/accuracy tradeoff in force perception.
AB  - There is a well-known tradeoff between speed and accuracy in judgments made under
      uncertainty. Diffusion models have been proposed to capture the increase in
      response time for more uncertain decisions and the change in performance due to a
      prioritization of speed or accuracy in the responses. Experimental paradigms have
      been confined to the visual modality and model analysis have mostly used quantile
      probability (QP) plots--response probability as a function of quantized RTs.
      Here, we extend diffusion modeling to haptics and test a novel type of analysis
      for judging model fitting. Participants classified force stimuli applied to the
      hand as "high" or "low." Data in QP plots indicate that the diffusion model
      captures well the overall pattern of responses in conditions where either speed
      or accuracy has been prioritized. To further the analysis, we compute just
      noticeable difference (JND) values separately for responses delivered with
      different RTs--we define these plots as JND quantile. The pattern of results
      evidences that slower responses lead to better force discrimination up to a
      plateau that is unaffected by prioritization instructions. Instead, the diffusion
      model predicts two well-separated plateaus depending on the condition. We propose
      that analyzing the relation between JNDs and response time should be considered
      in the evaluation of the diffusion model beyond the haptic modality, thus
      including vision.

PMID- 25867513
TI  - Development of a quantitative recombinase polymerase amplification assay with an
      internal positive control.
AB  - It was recently demonstrated that recombinase polymerase amplification (RPA), an
      isothermal amplification platform for pathogen detection, may be used to quantify
      DNA sample concentration using a standard curve. In this manuscript, a detailed
      protocol for developing and implementing a real-time quantitative recombinase
      polymerase amplification assay (qRPA assay) is provided. Using HIV-1 DNA
      quantification as an example, the assembly of real-time RPA reactions, the design
      of an internal positive control (IPC) sequence, and co-amplification of the IPC
      and target of interest are all described. Instructions and data processing
      scripts for the construction of a standard curve using data from multiple
      experiments are provided, which may be used to predict the concentration of
      unknown samples or assess the performance of the assay. Finally, an alternative
      method for collecting real-time fluorescence data with a microscope and a stage
      heater as a step towards developing a point-of-care qRPA assay is described. The
      protocol and scripts provided may be used for the development of a qRPA assay for
      any DNA target of interest. 

PMID- 25867514
TI  - TLR-3 is present in human adipocytes, but its signalling is not required for
      obesity-induced inflammation in adipose tissue in vivo.
AB  - Innate immunity plays a pivotal role in obesity-induced low-grade inflammation
      originating from adipose tissue. Key receptors of the innate immune system
      including Toll-like receptors-2 and -4 (TLRs) are triggered by nutrient excess to
      promote inflammation. The role of other TLRs in this process is largely unknown.
      In addition to double-stranded viral mRNA, TLR-3 can also recognize mRNA from
      dying endogenous cells, a process that is frequently observed within obese
      adipose tissue. Here, we identified profound expression of TLR-3 in adipocytes
      and investigated its role during diet-induced obesity. Human adipose tissue
      biopsies (n=80) and an adipocyte cell-line were used to study TLR-3 expression
      and function. TLR-3-/- and WT animals were exposed to a high-fat diet (HFD) for
      16 weeks to induce obesity. Expression of TLR-3 was significantly higher in human
      adipocytes compared to the non-adipocyte cells part of the adipose tissue. In
      vitro, TLR-3 expression was induced during differentiation of adipocytes and
      stimulation of the receptor led to elevated expression of pro-inflammatory
      cytokines. In vivo, TLR-3 deficiency did not significantly influence HFD-induced
      obesity, insulin sensitivity or inflammation. In humans, TLR-3 expression in
      adipose tissue did not correlate with BMI or insulin sensitivity (HOMA-IR).
      Together, our results demonstrate that TLR-3 is highly expressed in adipocytes
      and functionally active. However, TLR-3 appears to play a redundant role in
      obesity-induced inflammation and insulin resistance. 

PMID- 25867516
TI  - Microbially-driven strategies for bioremediation of bauxite residue.
AB  - Globally, 3 Gt of bauxite residue is currently in storage, with an additional 120
      Mt generated every year. Bauxite residue is an alkaline, saline, sodic, massive,
      and fine grained material with little organic carbon or plant nutrients. To date,
      remediation of bauxite residue has focused on the use of chemical and physical
      amendments to address high pH, high salinity, and poor drainage and aeration. No
      studies to date have evaluated the potential for microbial communities to
      contribute to remediation as part of a combined approach integrating chemical,
      physical, and biological amendments. This review considers natural alkaline,
      saline environments that present similar challenges for microbial survival and
      evaluates candidate microorganisms that are both adapted for survival in these
      environments and have the capacity to carry out beneficial metabolisms in bauxite
      residue. Fermentation, sulfur oxidation, and extracellular polymeric substance
      production emerge as promising pathways for bioremediation whether employed
      individually or in combination. A combination of bioaugmentation (addition of
      inocula from other alkaline, saline environments) and biostimulation (addition of
      nutrients to promote microbial growth and activity) of the native community in
      bauxite residue is recommended as the approach most likely to be successful in
      promoting bioremediation of bauxite residue.

PMID- 25867517
TI  - Treatment of Acute Necrotizing Fasciitis Using Negative Pressure Wound Therapy
      and Adjunctive NeutroPhase Irrigation Under the Foam.
AB  - Necrotizing fasciitis is a complication of a bacterial infection that activates
      the immune system in perifascial planes. This case report highlights initial
      diagnostic failures that delay early treatment, which causes profoundly negative
      consequences. Antimicrobial control with abolition of the inciting bacteria does
      not neutralize the subsequent endopathologic ravages. A new therapeutic
      technique, which combines negative pressure wound therapy (NPWT) and a pure
      hypochlorous acid solution 0.01% (NeutroPhase, NovaBay Pharmaceuticals Inc,
      Emeryville, CA) along with debridement and antibiotics is described in this
      study. It is believed that the combination of neutralization of the toxins
      produced by bacteria with NeutroPhase along with the NPWT action of removing
      exudates is effective in saving the patient. 

PMID- 25867515
TI  - Arachidonic acid and docosahexaenoic acid suppress osteoclast formation and
      activity in human CD14+ monocytes, in vitro.
AB  - An unbalanced diet can have adverse effects on health. Long chain polyunsaturated
      fatty acids (LCPUFAs) have been the focus of research owing to their necessity of
      inclusion in a healthy diet. However, the effects of LCPUFAs on human osteoclast
      formation and function have not been explored before. A human CD14+ monocyte
      differentiation model was used to elucidate the effects of an omega-3 LCPUFA,
      docosahexaenoic acid (DHA), and an omega-6 LCPUFA, arachidonic acid (AA), on
      osteoclast formation and activity. CD14+ monocytes were isolated from peripheral
      blood of healthy donors and stimulated with macrophage colony stimulating factor
      and receptor activator of nuclear factor kappa-B ligand to generate osteoclasts.
      Data from this study revealed that both the LCPUFAs decreased osteoclast
      formation potential of CD14+ monocytes in a dose-dependent manner when treated at
      an early stage of differentiation. Moreover, when exposed at a late stage of
      osteoclast differentiation AA and DHA impaired the bone resorptive potential of
      mature osteoclasts without affecting osteoclast numbers. AA and DHA abrogated
      vitronectin receptor expression in differentiating as well as mature osteoclasts.
      In contrast, the degree of inhibition for calcitonin receptor expression varied
      between the LCPUFAs with only AA causing inhibition during osteoclast
      differentiation. Furthermore, AA and DHA down regulated the expression of key
      osteoclast-specific genes in differentiating as well as mature osteoclasts. This
      study demonstrates for the first time that LCPUFAs can modulate osteoclast
      formation and function in a human primary osteoclast cell line. 

PMID- 25867518
TI  - Is estrogen effective for full-thickness cutaneous wound healing in young male
      mice?
AB  - The aim of this study is to show the effects of estrogen upon its topical
      application on the wound healing process in young male mice. Fifty-six male mice
      aged 7 weeks old were divided into 4 groups: sham operation, castration, estrogen
      treatment after sham operation, and estrogen treatment after castration. Wound
      healing was observed daily until day 14 after wounding. Specimens were harvested
      on days 3, 7, 10, and 14, and stained to evaluate reepithelialization,
      inflammation, contraction, and collagenaccumulation. Wound healing periods of all
      groups were almost the same, although the concentration of serum estrogen in the
      estrogen-applied mice was very high, and that in the nonapplied groups was low.
      The numbers of macrophages in the castrated, estrogen-treated after sham
      operation, and estrogen-treated after castration groups were significantly
      decreased compared with that in the sham group in the inflammatory phase;
      however, the ratio of wound area in these groups did not decrease, and other
      histological data did not reveal any effects of estrogen. These results indicate
      that estrogen may show limited effectiveness for full-thickness cutaneous wound
      healing in young male mice, and decreased inflammation may not always be
      associated with decreased wound area.    . 

PMID- 25867519
TI  - Pressure relief with visco-elastic foam or with combined static air overlay? A
      prospective, crossover randomized clinical trial in a dutch nursing home.
AB  - OBJECTIVE: Evidence of the best mattress for preventing pressure ulcers is not
      conclusive. In a single center, prospective, crossover trial on pressure ulcer
      incidence in nursing home residents, a static air overlay mattress, without a
      pump, on top of a visco-elastic foam mattress was compared with a visco-elastic
      foam mattress alone. METHODS: The study was performed using a randomized
      crossover design. Forty-one patients with a score of 19 or lower on the Braden
      scale, but with no pressure ulcer at the start, were divided into 2 groups; 21
      patients received a visco-elastic foam mattress (control group) and 20 patients a
      static air overlay on top of a visco-elastic foam mattress (intervention group)
      for a period of 6 months. In the second (crossover) period of 6 months, 19
      patients participated in each group. Patients were checked weekly and, only when
      signs of development of a pressure ulcer were present was treatment altered to
      reposition patients according to the nursing home pressure ulcer protocol. No
      statistically significant differences were noted between the 2 groups with regard
      to age, gender, or Braden scale score. RESULTS: Of 41 patients, 3 died and were
      unable to participate in the crossover period, 8 patients (22.2%) developed a
      category 2 or higher pressure ulcer on a visco-elastic foam mattress (control
      group) and 2 (5.2%) on a static air mattress (intervention group)(P = 0.087).
      There was a difference regarding pressure ulcer incidence between patients with a
      very low Braden score between 6 and 12, and patients with a mean score between 13
      19. Out of 8 patients, in the 2(25%) who developed a pressure ulcer on a foam
      mattress, the ulcers showed no signs of healing. In the static air group all
      pressure ulcers healed by normal treatment according to a standardized pressure
      ulcer treatment protocol. CONCLUSIONS: In this small study, static air overlay
      mattresses provided a better prevention than visco-elastic foam mattresses alone
      (5.2% vs 22.2%). The Braden scores of the patients in both groups did not change
      during the 6-month test. The decision to use repositioning only when there were
      signs of a pressure ulcer is acceptable when a static air overlay is in position.
      The 22.2% incidence of pressure ulcers in the foam group, however, may stress the
      need to continue repositioning when using this type of mattress.  .

PMID- 25867520
TI  - Silver dressings improve diabetic wound healing without reducing bioburden.
AB  - Introduction. Silver dressings are widely used in the treatment of chronic
      wounds to reduce bacterial bioburden. However, little is known about the
      mechanism of silver ions on the healing process. In this study, a mouse model of
      wound healing was used to examine the effect of silver dressings in normal and
      diabetic wounds. METHODS: Two 5-mm full-thickness wounds were created on the
      dorsal skin of diabetic BKS.Cg- m+/+Leprdb/J mice (experimental group) and wild
      type C57BL/6 mice (control group), and treated with either a silver or gauze
      dressing. Measurement of wound areas by digital planimetry demonstrated faster
      healing in the silver-treated wounds of both diabetic and control mice. RESULTS:
      Quantitative bacterial cultures showed a reduction of bioburden in silver-treated
      wounds in wild type mice. Unexpectedly, there was no decrease in bioburden in the
      silver-treated diabetic wounds compared to the control diabetic wounds, despite
      improved healing in the silver-treated diabetic wounds. Staphylococcus xylosus, a
      known biofilm producer, was the only bacteria identified in all the wounds. In
      vitro studies showed S. xylosus produced biofilms faster in higher glucose
      environments; this may explain the increased bioburden in the wounds in diabetic
      mice compared to wild type mice. CONCLUSION: The results demonstrate improved
      healing and reduced bioburden in normal wounds with silver dressings. In
      contrast, silver dressings improved healing in diabetic wounds despite no effect
      on bioburden, suggesting silver may have beneficial effects in addition to its
      antimicrobial properties.

PMID- 25867521
TI  - Assessing transmissible spongiform encephalopathy species barriers with an in
      vitro prion protein conversion assay.
AB  - Studies to understanding interspecies transmission of transmissible spongiform
      encephalopathies (TSEs, prion diseases) are challenging in that they typically
      rely upon lengthy and costly in vivo animal challenge studies. A number of in
      vitro assays have been developed to aid in measuring prion species barriers,
      thereby reducing animal use and providing quicker results than animal bioassays.
      Here, we present the protocol for a rapid in vitro prion conversion assay called
      the conversion efficiency ratio (CER) assay. In this assay cellular prion protein
      (PrPC) from an uninfected host brain is denatured at both pH 7.4 and 3.5 to
      produce two substrates. When the pH 7.4 substrate is incubated with TSE agent,
      the amount of PrPC that converts to a proteinase K (PK)-resistant state is
      modulated by the original host's species barrier to the TSE agent. In contrast,
      PrPC in the pH 3.5 substrate is misfolded by any TSE agent. By comparing the
      amount of PK-resistant prion protein in the two substrates, an assessment of the
      host's species barrier can be made. We show that the CER assay correctly predicts
      known prion species barriers of laboratory mice and, as an example, show some
      preliminary results suggesting that bobcats (Lynx rufus) may be susceptible to
      white-tailed deer (Odocoileus virginianus) chronic wasting disease agent.

PMID- 25867522
TI  - Complex of GM1- and GD1a-like lipo-oligosaccharide mimics GM1b, inducing anti
      GM1b antibodies.
AB  - OBJECTIVE: Molecular mimicry between Campylobacter jejuni lipo-oligosaccharides
      (LOSs) and human gangliosides GM1 and GD1a induces the production of anti-GM1 and
      anti-GD1a antibodies, and the development of Guillain-Barre syndrome. Complexes
      of two different gangliosides form new molecular shapes capable of enhancing
      recognition by anti-ganglioside antibodies. To test the hypothesis that the
      complex of GM1-like and GD1a-like LOSs of C. jejuni induces the development of
      anti-GM1b antibodies in Guillain-Barre syndrome patients. METHODS: Mass
      spectrometry analysis determined the LOS outer core structures, with which mice
      were immunized. IgG antibodies to single gangliosides and complex of gangliosides
      were tested in sera from Guillain-Barre syndrome patients from whom C. jejuni LOS
      had been isolated. RESULTS: Two isolates from GBS patients who had anti-GM1b
      antibodies, but neither anti-GM1 nor -GD1a antibodies, expressed both GM1-like
      and GD1a-like LOSs, but not GM1b-like LOS. Anti-GM1b antibodies were induced in
      one of the mice immunized with the C. jejuni bearing GM1-like and GD1a-like LOS.
      Sera from 20 patients had antibodies to the complex of GM1 and GD1a, all of which
      carried anti-GM1b reactivity. Five of these sera harbored neither anti-GM1 nor
      anti-GD1a antibodies. IgG antibodies to the complex were absorbed by GM1b, but by
      neither GM1 nor GD1a. CONCLUSIONS: GM1-like and GD1a-like LOSs form a GM1b
      epitope, inducing the development of anti-GM1b antibodies in patients with
      Guillain-Barre syndrome subsequent to C. jejuni enteritis. Here, we present a new
      paradigm that the complex of two different structures forms a new molecular
      mimicry, inducing the production of autoantibodies.

PMID- 25867523
TI  - Functional characterization of Na+/H+ exchangers of intracellular compartments
      using proton-killing selection to express them at the plasma membrane.
AB  - Endosomal acidification is critical for a wide range of processes, such as
      protein recycling and degradation, receptor desensitization, and neurotransmitter
      loading in synaptic vesicles. This acidification is described to be mediated by
      proton ATPases, coupled to ClC chloride transporters. Highly-conserved
      electroneutral protons transporters, the Na+/H+ exchangers (NHE) 6, 7 and 9 are
      also expressed in these compartments. Mutations in their genes have been linked
      with human cognitive and neurodegenerative diseases. Paradoxically, their roles
      remain elusive, as their intracellular localization has prevented detailed
      functional characterization. This manuscript shows a method to solve this
      problem. This consists of the selection of mutant cell lines, capable of
      surviving acute cytosolic acidification by retaining intracellular NHEs at the
      plasma membrane. It then depicts two complementary protocols to measure the ion
      selectivity and activity of these exchangers: (i) one based on intracellular pH
      measurements using fluorescence video microscopy, and (ii) one based on the fast
      kinetics of lithium uptake. Such protocols can be extrapolated to measure other
      non-electrogenic transporters. Furthermore, the selection procedure presented
      here generates cells with an intracellular retention defective phenotype.
      Therefore these cells will also express other vesicular membrane proteins at the
      plasma membrane. The experimental strategy depicted here may therefore constitute
      a potentially powerful tool to study other intracellular proteins that will be
      then expressed at the plasma membrane together with the vesicular Na+/H+
      exchangers used for the selection.

PMID- 25867524
TI  - Donor-Acceptor Copolymers Based on Thermally Cleavable Indigo, Isoindigo, and DPP
      Units: Synthesis, Field Effect Transistors, and Polymer Solar Cells.
AB  - A series of donor-acceptor type of pi-conjugated copolymers based on tert
      butoxycarbonyl (t-Boc) substituted indigo, isoindigo or diketopyrrolopyrrole as
      the acceptor unit and a benzodithiophene derivative as the donor unit was
      designed and synthesized. These copolymers can be readily dissolved in organic
      solvents and can produce uniform films by solution deposition. Thermal treatment
      of copolymer films at 200  degrees C for 10 min resulted in elimination of t-Boc
      side groups in nearly quantitative yield as suggested by thermogravimetric
      analysis and Fourier transform infrared spectroscopy. The elimination of the
      bulky t-Boc side groups resulted in the emergence of N-H...O?C hydrogen bonding
      interactions by virtue of the lactam structures of the indigo, isoindigo and
      diketopyrrolopyrrole units. Of particular interests is the distinctly increased
      field-effect mobility of these copolymers after thermal treatment, which may
      arise from the enhanced coplanarity and intermolecular ordering of the indigo,
      isoindigo or diketopyrrolopyrrole units after elimination of the bulky t-Boc side
      groups. These results demonstrate that the incorporation of latent side groups
      provides a viable strategy to construct conjugated polymers that can attain more
      ordered intermolecular stacking by simple thermal treatments. On the other hand,
      despite the thermal cleavage of t-Boc groups can also lead to increased ordering
      of polymer chains when blending with [6,6]-phenyl C71 butyric acid methyl ester,
      the photovoltaic performances of the resulting bulk heterojunction solar cells
      did not obviously increase due to the serious phase separation and coarsening of
      the film morphology. 

PMID- 25867525
TI  - Social anxiety and associations with eating psychopathology: Mediating effects of
      fears of evaluation.
AB  - Recent work suggests unique relations among features of social anxiety disorder
      and eating disorder pathology. Thus, it may be important to determine specific
      facets of social anxiety that account for the relation between it and eating
      disorders. Given the similarities in social-evaluative concerns in both sets of
      symptoms, we hypothesized that fears of both positive and negative evaluation
      would each independently account for the relationship between social anxiety
      symptoms and eating pathology among college females (N=167). Results were
      partially supportive of hypotheses. Fear of negative evaluation independently
      accounted for a significant portion of the relationship between social anxiety
      and each domain of eating pathology that was tested, which included Drive for
      Thinness, Body Dissatisfaction, and Bulimic Symptoms. Body mass index appeared to
      play a moderating role on the relationship between fear of negative evaluation
      and body dissatisfaction, but not drive for thinness or bulimia symptoms.
      Clinical implications including diagnostic and treatment considerations will be
      discussed. 

PMID- 25867526
TI  - Examining impulsivity as a moderator of the relationship between body shame and
      bulimic symptoms in Black and White young women.
AB  - Impulsivity has been linked to bulimic symptomatology in a number of studies;
      however, few have examined this relationship among Black women. We investigated
      the correlations between impulsivity and bulimic symptoms, and tested impulsivity
      as a moderator of the body shame/bulimic symptoms relationship among a sample of
      female undergraduates (N=276; 97 Blacks, 179 Whites). These participants provided
      data on body shame, impulsivity, and bulimic symptoms (EDE-Q binge eating
      frequency, BULIT-R, EDI-Bulimia). Among Blacks, impulsivity was significantly
      positively associated with all bulimic symptoms measures; among Whites,
      impulsivity was only positively correlated with binge eating frequency.
      Furthermore, among Blacks, the combination of high body shame and high
      impulsivity was associated with the highest levels of bulimic symptoms; these
      findings were not observed among Whites. This study highlights the importance of
      impulsivity and body shame in identifying bulimic symptomatology among Black
      women. 

PMID- 25867527
TI  - Confirmatory factor analysis and psychometric properties of the Spanish version
      of the Multidimensional Body-Self Relations Questionnaire-Appearance Scales.
AB  - The Multidimensional Body-Self Relations Questionnaire (MBSRQ) is the most
      comprehensive instrument to assess body image. The MBSRQ-Appearance Scales (MBSRQ
      AS) is a reduced version that has been validated in other languages. The main aim
      of the present study was to confirm the factor structure of the Spanish version
      of the MBSRQ-AS and analyze its psychometric properties in 1041 nonclinical
      individuals. Confirmatory factor analysis showed excellent goodness of fit
      indices for the five-factor structure (Appearance Evaluation, Appearance
      Orientation, Body Areas Satisfaction, Overweight Preoccupation, and Self
      Classified Weight). Factors possessed adequate scale score reliability indices.
      Some of the factors showed significant associations with the Eating Attitudes
      Test. Significant differences were found between boys/men and girls/women, and
      among age groups. The Spanish version of the MBSRQ-AS is a valid instrument for
      use in nonclinical population settings in people from 15 to 46 years old. 

PMID- 25867528
TI  - Novel assessment of haemodynamic kinetics with acute exercise in a rat model of
      pulmonary arterial hypertension.
AB  - NEW FINDINGS: What is the central question of this study? The acute effect of
      exercise at moderately high intensity on already-elevated pulmonary arterial
      pressures and right ventricular wall stress in a rat model of pulmonary arterial
      hypertension (PAH) is unknown. What is the main finding and its importance? We
      show, for the first time, that in a rat model of PAH, exercise induces an acute
      reduction in pulmonary artery pressure associated with lung endothelial nitric
      oxide synthase activation, without evidence of acute right ventricular
      inflammation or myocyte apoptosis. Haemodynamic measures obtained with
      traditional invasive methodology as well as novel implantable telemetry reveal an
      exercise-induced 'window' of pulmonary hypertension alleviation, supporting
      future investigations of individualized exercise as therapy in PAH. Exercise
      improves outcomes of multiple chronic conditions, but controversial results,
      including increased pulmonary artery (PA) pressure, have prevented its routine
      implementation in pulmonary arterial hypertension (PAH), an incurable disease
      that drastically reduces exercise tolerance. Individualized, optimized exercise
      prescription for PAH requires a better understanding of disease-specific exercise
      responses. We investigated the acute impact of exercise on already-elevated PA
      pressure and right ventricular (RV) wall stress and inflammation in a rat model
      of PAH (PAH group, n = 12) induced once by monocrotaline (50 mg kg(-1) , i.p.; 2
      weeks), compared with healthy control animals (n = 8). Single bouts of exercise
      consisted of a 45 min treadmill run at 75% of individually determined aerobic
      capacity (VO2max). Immediately after exercise, measurements of RV systolic
      pressure and systemic pressure were made via jugular and carotid cannulation, and
      were followed by tissue collection. Monocrotaline induced moderate PAH, evidenced
      by RV hypertrophy, decreased VO2max, PA muscularization, and RV and skeletal
      muscle cytoplasmic glycolysis detected by increased expression of glucose
      transporter-1. Acute exercise normalized the monocrotaline-induced elevation in
      RV systolic pressure and augmented pulmonary endothelial nitric oxide synthase
      activation, without evidence of increased RV inflammation or apoptosis. Real-time
      recordings of pulmonary and systemic pressures during and after single bouts of
      exercise made using novel implantable telemetry in the same animal for up to 11
      weeks after monocrotaline (40 mg kg(-1) ) corroborated the finding of acute PA
      pressure decreases with exercise in PAH. The PA pressure-lowering effects of
      individualized exercise associated with RV-neutral effects and increases in
      vasorelaxor signalling encourage further development of optimized exercise
      regimens as adjunctive PAH therapy.

PMID- 25867529
TI  - Neutrophil chemotaxis in cord blood of term and preterm neonates is reduced in
      preterm neonates and influenced by the mode of delivery and anaesthesia.
AB  - Bacterial infections, even without any perinatal risk factors, are common in
      newborns, especially in preterm neonates. The aim of this study was to evaluate
      possible impairment of neutrophil chemotaxis in term and preterm neonates
      compared with adults as well as neonates with different modes of delivery and
      anaesthesia. We analysed the expression of the adhesion molecule L-Selectin as
      well as shape change, spontaneous and N-formyl-methionyl-leucyl-phenylalanine
      (fMLP)-induced transmigration of neutrophils in a flow cytometric assay of
      chemotaxis after spontaneous delivery with Cesarian Section (CS) under spinal
      anaesthesia (mepivacaine, sufentanil), epidural anaesthesia (ropivacaine or
      bupivacaine, sufentanil) or general anaesthesia (ketamine, thiopental,
      succinylcholine). Chemokinesis was higher (p=0.008) in cord blood neutrophils
      than in the adult ones, whereas those could be more stimulated by fMLP (p=0.02).
      After vaginal delivery neutrophils showed a higher spontaneous and fMLP
      stimulated chemotactic response compared to neonates after CS without labor.
      Comparing different types of anaesthesia for CS, spinal anaesthesia resulted in
      less impairment on chemotaxis than general anaesthesia or epidural anaesthesia.
      The new flow cytometric assay of neutrophil chemotaxis is an appropriate and
      objective method to analyse functional differences even in very small volumes of
      blood, essential in neonatology. Term neonates do not show reduced chemotaxis
      compared to adults. Preterm neonates present with reduced chemotaxis and
      chemokinesis, confirming the well known deficits in their neutrophil function.
      The side effects of maternal drugs on the neonatal immune system have to be
      considered especially when the immune response is already impaired, as in preterm
      infants. 

PMID- 25867530
TI  - Levosimendan displays anti-inflammatory effects and decreases MPO bioavailability
      in patients with severe heart failure.
AB  - Treatment of decompensated heart failure often includes administration of
      levosimendan. Myeloperoxidase (MPO) is released during polymorphonuclear
      neutrophil (PMN) degranulation, and mediates dysregulation of vascular tone in
      heart failure. We evaluated the effects of levosimendan-treatment on MPO in
      patients with acute decompensation of chronic heart failure over a one week
      course. Plasma MPO levels were significantly decreased after levosimendan
      treatment (from 252.1 +/- 31.1 pmol/l at baseline to 215.02 +/- 27.96 pmol/l at 6
      h, p < 0.05). Ex vivo incubation of whole blood with levosimendan decreased MPO
      release after PMN-stimulation (8.2 +/- 1.4-fold increase at baseline vs. 6.0 +/-
      1.1-fold increase with levosimendan). MPO levels also significantly correlated
      with diastolic blood pressure over the time course. In a multivariate linear
      model, the main contributor to systolic, diastolic and mean blood pressure was
      level of PMN elastase. MPO contributed only in heparin-treated patients,
      suggesting a more significant role for endothelial-bound MPO than for circulating
      MPO or elastase with respect to blood pressure regulation. We here provide the
      first evidence that levosimendan treatment inhibits MPO release by PMNs in
      decompensated heart failure patients. This mechanism may regulate endothelial
      function and vascular tone in heart failure patients. 

PMID- 25867531
TI  - Surgical method for virally mediated gene delivery to the mouse inner ear through
      the round window membrane.
AB  - Gene therapy, used to achieve functional recovery from sensorineural deafness,
      promises to grant better understanding of the underlying molecular and genetic
      mechanisms that contribute to hearing loss. Introduction of vectors into the
      inner ear must be done in a way that widely distributes the agent throughout the
      cochlea while minimizing injury to the existing structures. This manuscript
      describes a post-auricular surgical approach that can be used for mouse cochlear
      therapy using molecular, pharmacologic, and viral delivery to mice postnatal day
      10 and older via the round window membrane (RWM). This surgical approach enables
      rapid and direct delivery into the scala tympani while minimizing blood loss and
      avoiding animal mortality. This technique involves negligible or no damage to
      essential structures of the inner and middle ear as well as neck muscles while
      wholly preserving hearing. To demonstrate the efficacy of this surgical
      technique, the vesicular glutamate transporter 3 knockout (VGLUT3 KO) mice will
      be used as an example of a mouse model of congenital deafness that recovers
      hearing after delivery of VGLUT3 to the inner ear using an adeno-associated virus
      (AAV-1). 

PMID- 25867532
TI  - A Network Meta-analysis of Randomized Controlled Trials Focusing on Different
      Allergic Rhinitis Medications.
AB  - This study is aimed to investigate the effectiveness of 4 allergic rhinitis (AR)
      drugs (loratadine, cetirizine, montelukast, and desloratadine) in reducing
      functional problems in patients, as indicated by rhinoconjunctivitis quality of
      life questionnaire scores. After an exhaustive search of electronic databases
      containing published scientific literature, high-quality randomized controlled
      trials relevant to our study were selected based on a stringent predefined
      inclusion and exclusion criteria. Statistical analyses were conducted using STATA
      12.0 and comprehensive meta-analysis (CMA 2.0) software. The literature search
      broadly identified 386 studies, and after a multistep screening and elimination
      process, a total of 13 randomized controlled trials contributed to this network
      meta-analysis. These 13 high-quality studies contained a combined total of 6867
      patients with AR on 4 different medications. The results of network meta-analysis
      revealed that, compared with placebo, all 4 mediations treated AR effectively
      [cetirizine: mean: -0.62, 95% confidence intervals (95% CI) = -0.90 to -0.34, P <
      0.001; loratadine: mean: -0.32, 95% CI = -0.55 to -0.097, P = 0.005; montelukast:
      mean: -0.28, 95% CI = -0.54 to -0.023, P = 0.033; desloratadine: mean: -0.39, 95%
      CI = -0.60 to -0.18, P < 0.001]. A comparison of surface under the cumulative
      ranking curve values of these 4 interventions clearly showed that cetirizine is
      the most optimal medication for AR treatment. In conclusion, this network meta
      analysis provides the first evidence that cetirizine is the most efficacious
      treatment for AR compared with loratadine, montelukast, and desloratadine,
      significantly reducing the functional problems in patients with AR.

PMID- 25867533
TI  - Academic Detailing Interventions Improve Tobacco Use Treatment among Physicians
      Working in Underserved Communities.
AB  - RATIONALE: Tobacco use disproportionately affects the poor, who are, in turn,
      least likely to receive cessation treatment from providers. Providers caring for
      low-income populations perform simple components of tobacco use treatment (e.g.,
      assessing tobacco use) with reasonable frequency. However, performance of complex
      treatment behaviors, such as pharmacologic prescription and follow-up
      arrangement, remains suboptimal. OBJECTIVES: Evaluate the influence of academic
      detailing (AD), a university-based, noncommercial, educational outreach
      intervention, on primary care physicians' complex treatment practice behaviors
      within an urban care setting. METHODS: Trained academic detailers made in-person
      visits to targeted primary care practices, delivering verbal and written
      instruction emphasizing three key messages related to tobacco treatment.
      Physicians' self-reported frequency of simple and complex treatment behaviors
      were assessed using a seven-item questionnaire, before and 2 months after AD.
      RESULTS: Between May 2011 and March 2012, baseline AD visits were made to 217
      physicians, 109 (50%) of whom also received follow-up AD. Mean frequency scores
      for complex behaviors increased significantly, from 2.63 to 2.92, corresponding
      to a clinically significant 30% increase in the number of respondents who
      endorsed "almost always" or "always" (P < 0.001). Improvement in mean simple
      behavior frequency scores was also noted (3.98 vs. 4.13; P = 0.035). Sex and
      practice type appear to influence reported complex behavior frequency at
      baseline, whereas only practice type influenced improvement in complex behavior
      scores at follow up. CONCLUSIONS: This study demonstrates the feasibility and
      potential effectiveness of a low-cost and highly disseminable intervention to
      improve clinician behavior in the context of treating nicotine dependence in
      underserved communities.

PMID- 25867534
TI  - Healthy term and moderately preterm infants have similar cerebral oxygen
      saturation and cerebral blood flow volumes during early post-natal transition.
AB  - AIM: This pilot study evaluated changes in regional cerebral oxygen saturation
      and cerebral blood flow volume during the transitional period in healthy term and
      moderately preterm infants. METHODS: The cohort comprised 16 preterm infants and
      seven full-term infants with mean gestational ages of 34 and 39 weeks,
      respectively. Longitudinal measurements were conducted during the first three
      days after birth. Regional cerebral oxygen saturation was determined bilaterally
      by frequency domain near-infrared spectroscopy. Flow volumes were determined in
      internal carotid and vertebral arteries by multiplying the time-averaged velocity
      by the cross-sectional area: cerebral blood flow volume was calculated as the sum
      of flow volumes and adjusted for brain weight. RESULTS: Brain weight-adjusted
      cerebral blood flow volumes and regional cerebral oxygen saturation were similar
      in preterm and term infants. Regional cerebral oxygen saturation did not
      correlate with brain weight-adjusted cerebral blood flow volume. Right and left
      brain weight-adjusted internal carotid flow volumes did not correlate with right
      and left regional cerebral oxygen saturation. CONCLUSION: Our findings suggest
      that during the first three days after birth there was adequate cardiorespiratory
      adaptation, cerebral perfusion and adequate compensation through the arterial
      circle of Willis in both healthy term and moderately preterm infants.

PMID- 25867535
TI  - Cosolvent approach for solution-processable electronic thin films.
AB  - Low-temperature solution-processable electronic materials are of considerable
      interest for large-area, low-cost electronics, thermoelectrics, and
      photovoltaics. Using a soluble precursor and suitable solvent to formulate a
      semiconductor ink is essential for large-area fabrication of semiconductor thin
      films. To date, it has been shown that hydrazine can be used as a versatile
      solvent to process a wide range of inorganic semiconductors. However, hydrazine
      is highly toxic and not suitable for large-scale manufacturing. Here we report a
      binary mixed solvent of amine and thiol for effective dispersion and dissolution
      of a large number of inorganic semiconductors including Cu2S, Cu2Se, In2S3,
      In2Se3, CdS, SnSe, and others. The mixed solvent is significantly less toxic and
      safer than hydrazine, while at the same time offering the comparable capability
      of formulating diverse semiconductor ink with a concentration as high as >200
      mg/mL. We further show that such ink material can be readily processed into high
      performance semiconducting thin films (Cu2S and Cu2Se) with the highest room
      temperature conductivity among solution-based materials. Furthermore, we show
      that complex semiconductor alloys with tunable band gaps, such as CuIn(S(x)Se(1
      x))2 (0 <= x <= 1), can also be readily prepared by simply mixing Cu2S, Cu2Se,
      In2S3, and In2Se3 ink solutions in a proper ratio. Our study outlines a general
      strategy for the formulation of inorganic semiconductor ink for low-temperature
      processing of large-area electronic thin films on diverse substrates and can
      greatly impact diverse areas including flexible electronics, thermoelectrics, and
      photovoltaics.

PMID- 25867537
TI  - Prospective cohort study of clinical characteristics and management patterns for
      patients with non-small-cell lung cancer in the Russian Federation: EPICLIN-Lung.
AB  - BACKGROUND: Lung cancer is a major cause of mortality in Russia. This study aimed
      to document the characteristics, clinical management, EGFR mutation status and
      outcomes of patients with non-small-cell lung cancer (NSCLC) throughout the
      Russian Federation to inform future management decisions. METHODS: This non
      interventional, prospective cohort study (clinicaltrials.gov NCT01069835) was
      conducted at 33 sites across the Russian Federation. Patients with confirmed
      NSCLC were enrolled and followed for up to 12 months or until death.
      Investigators collected information on patient and disease characteristics,
      diagnosis and treatment patterns, clinical outcomes and adverse events (AEs). A
      logistic regression model was used to evaluate characteristics affecting tumor
      EGFR mutation status. RESULTS: Data were analyzed from 838 patients. Most (78.4%)
      were male and Caucasian (98%), mean age was 58.7 years and 26.5% were never
      smokers. Squamous-cell carcinoma (54.3%) was the most prevalent histology,
      followed by adenocarcinoma (31%). Most patients presented with advanced disease
      (23.7% with stage IIIA, 14.1% with stage IIIB, 25.4% with stage IV) and 10.1% of
      patients had EGFR-mutation-positive tumors. EGFR mutation was significantly
      associated with female gender, never smoking, age and adenocarcinoma histology.
      First- or second-line chemotherapy had been performed in 370 and 96 patients,
      respectively, and median progression-free survival was 35 and 19.4 weeks,
      respectively. For 813 patients, 194 AEs were reported at visit 1. A median of two
      AEs was reported for patients who had at least one AE. Study limitations include
      potential site selection bias, short observation period, small sample size and
      inclusion of fewer than average stage III-IV patients. CONCLUSIONS: This study
      contributes to a better understanding of prognostic and predictive factors of
      NSCLC in the Russian Federation, which will enable optimal treatment selection in
      future clinical practice. Epidemiology of EGFR mutations in this NSCLC cohort was
      similar to other studies of NSCLC in Caucasian populations.

PMID- 25867539
TI  - Dissecting Redox Biology Using Fluorescent Protein Sensors.
AB  - SIGNIFICANCE: Fluorescent protein sensors have revitalized the field of redox
      biology by revolutionizing the study of redox processes in living cells and
      organisms. RECENT ADVANCES: Within one decade, a set of fundamental new insights
      has been gained, driven by the rapid technical development of in vivo redox
      sensing. Redox-sensitive yellow and green fluorescent protein variants (rxYFP and
      roGFPs) have been the central players. CRITICAL ISSUES: Although widely used as
      an established standard tool, important questions remain surrounding their
      meaningful use in vivo. We review the growing range of thiol redox sensor
      variants and their application in different cells, tissues, and organisms. We
      highlight five key findings where in vivo sensing has been instrumental in
      changing our understanding of redox biology, critically assess the interpretation
      of in vivo redox data, and discuss technical and biological limitations of
      current redox sensors and sensing approaches. FUTURE DIRECTIONS: We explore how
      novel sensor variants may further add to the current momentum toward a novel
      mechanistic and integrated understanding of redox biology in vivo. Antioxid.
      Redox Signal. 24, 680-712.

PMID- 25867538
TI  - Efficacy and safety of single-dose zoledronic acid for osteoporosis in frail
      elderly women: a randomized clinical trial.
AB  - IMPORTANCE: Eighty-five percent of institutionalized elderly people have
      osteoporosis and bone fracture rates 8 to 9 times higher than rates observed
      among community-dwelling elderly people. Nevertheless, most of these persons are
      left untreated and are excluded from pivotal osteoporosis trials. OBJECTIVE: To
      determine the efficacy and safety of zoledronic acid to treat osteoporosis in
      frail elderly women in long-term care facilities. DESIGN, SETTING, AND
      PARTICIPANTS: We conducted a 2-year, randomized, placebo-controlled, double
      blinded study from December 2007 through March 2012. Included were 181 women 65
      or older with osteoporosis, including those with cognitive impairment,
      immobility, and multimorbidity, who were living in nursing homes and assisted
      living facilities. INTERVENTIONS: One 5-mg dose of zoledronic acid or placebo
      intravenously and daily calcium and vitamin D supplementation. MAIN OUTCOMES AND
      MEASURES: Hip and spine bone mineral density (BMD) at 12 and 24 months and
      adverse events. RESULTS: There were no baseline differences in mean (SE) age
      (85.4 [0.6] years), BMD, or functional or cognitive status, but the treatment
      group included more participants with frailty, falls history, diabetes, and
      anticonvulsant medication use. Values for BMD were available for 87% of
      participants at 12 months and 73% at 24 months. Mean (SE) BMD changes were
      greater in the treatment group: 3.2 (0.7) and 3.9 (0.7) percentage-point
      differences in the total hip at 12 and 24 months, respectively (P < .01 for both
      comparisons), and 1.8 (0.7) and 3.6 (0.7) percentage-point differences at the
      spine (P < .01); adjusted analyses were similar. The treatment and placebo
      groups' fracture rates were 20% and 16%, respectively (OR, 1.30; 95% CI, 0.61
      2.78); mortality rates were 16% and 13% (OR, 1.24; 95% CI, 0.54-2.86). Groups did
      not differ in the proportion of single fallers (28% vs 24%; OR, 1.24; 95% CI,
      0.64-2.42; P = .52), but more participants in the treatment group had multiple
      falls (49% vs 35%; OR, 1.83; 95% CI, 1.01-3.33; P = .047); however, this
      difference was no longer significant when adjusted for baseline frailty.
      CONCLUSIONS AND RELEVANCE: In this group of frail elderly women with
      osteoporosis, 1 dose of zoledronic acid improved BMD over 2 years. The clinical
      importance of nonsignificant increases in fracture and mortality rates in the
      treatment group needs further study. Since it is not known whether such therapy
      reduces the risk of fracture in this cohort, any change in nursing home practice
      must await results of larger trials powered to assess fracture rates. TRIAL
      REGISTRATION: clinicaltrials.gov Identifier: NCT00558012.

PMID- 25867540
TI  - Tracking mouse bone marrow monocytes in vivo.
AB  - Real time multiphoton imaging provides a great opportunity to study cell
      trafficking and cell-to-cell interactions in their physiological 3-dimensionnal
      environment. Biological activities of immune cells mainly rely on their motility
      capacities. Blood monocytes have short half-life in the bloodstream; they
      originate in the bone marrow and are constitutively released from it. In
      inflammatory condition, this process is enhanced, leading to blood monocytosis
      and subsequent infiltration of the peripheral inflammatory tissues. Identifying
      the biomechanical events controlling monocyte trafficking from the bone marrow
      towards the vascular network is an important step to understand monocyte
      physiopathological relevance. We performed in vivo time-lapse imaging by two
      photon microscopy of the skull bone marrow of the Csf1r-Gal4VP16/UAS-ECFP
      (MacBlue) mouse. The MacBlue mouse expresses the fluorescent reporters enhanced
      cyan fluorescent protein (ECFP) under the control of a myeloid specific promoter,
      in combination with vascular network labelling. We describe how this approach
      enables the tracking of individual medullar monocytes in real time to further
      quantify the migratory behaviour within the bone marrow parenchyma and the
      vasculature, as well as cell-to-cell interactions. This approach provides novel
      insights into the biology of the bone marrow monocyte subsets and allows to
      further address how these cells can be influenced in specific pathological
      conditions.

PMID- 25867541
TI  - Chiral recognition of carboxylates by a static library of thiourea receptors with
      amino acid arms.
AB  - Chiral recognition is based on a large network of very subtle interactions whose
      outcome is difficult to predict. A combinatorial approach is therefore the most
      suitable to search for the most efficient receptor and obtain a structure
      enantioselectivity correlation. We synthesized a set of 12 receptors constructed
      with 1,9-diaminoantracene and alpha-amino acid esters, linked via thiourea
      groups. The association constants and enantioselectivities for the complexes with
      mandelate and N-acetylphenylalanine were determined by competitive NMR
      titrations. Association constants quite regularly depend on the substituents in
      the receptor structure, but the distribution of enantioselectivities across the
      library could not easily be rationalized. 

PMID- 25867542
TI  - Implications of Stein's Paradox for Environmental Standard Compliance Assessment.
AB  - The implications of Stein's paradox stirred considerable debate in statistical
      circles when the concept was first introduced in the 1950s. The paradox arises
      when we are interested in estimating the means of several variables
      simultaneously. In this situation, the best estimator for an individual mean, the
      sample average, is no longer the best. Rather, a shrinkage estimator, which
      shrinks individual sample averages toward the overall average is shown to have
      improved overall accuracy. Although controversial at the time, the concept of
      shrinking toward overall average is now widely accepted as a good practice for
      improving statistical stability and reducing error, not only in simple estimation
      problems, but also in complicated modeling problems. However, the utility of
      Stein's insights are not widely recognized in the environmental management
      community, where mean pollutant concentrations of multiple waters are routinely
      estimated for management decision-making. In this essay, we introduce Stein's
      paradox and its modern generalization, the Bayesian hierarchical model, in the
      context of environmental standard compliance assessment. Using simulated data and
      nutrient monitoring data from wadeable streams around the Great Lakes, we show
      that a Bayesian hierarchical model can improve overall estimation accuracy,
      thereby improving our confidence in the assessment results, especially for
      standard compliance assessment of waters with small sample sizes. 

PMID- 25867543
TI  - TALEN-mediated targeted mutagenesis produces a large variety of heritable
      mutations in rice.
AB  - CRISPR/Cas9 and TALEN are currently the two systems of choice for genome editing.
      We have studied the efficiency of the TALEN system in rice as well as the nature
      and inheritability of TALEN-induced mutations and found important features of
      this technology. The N287C230 TALEN backbone resulted in low mutation rates (0
      6.6%), but truncations in its C-terminal domain dramatically increased efficiency
      to 25%. In most transgenic T0 plants, TALEN produced a single prevalent mutation
      accompanied by a variety of low-frequency mutations. For each independent T0
      plant, the prevalent mutation was present in most tissues within a single tiller
      as well as in all tillers examined, suggesting that TALEN-induced mutations
      occurred very early in the development of the shoot apical meristem.
      Multigenerational analysis showed that TALEN-induced mutations were stably
      transmitted to the T1 and T2 populations in a normal Mendelian fashion. In our
      study, the vast majority of TALEN-induced mutations (~81%) affected multiple
      bases and ~70% of them were deletions. Our results contrast with published
      reports for the CRISPR/Cas9 system in rice, in which the predominant mutations
      affected single bases and deletions accounted for only 3.3% of the overall
      mutations.

PMID- 25867545
TI  - Bandgap Widening of Phase Quilted, 2D MoS2 by Oxidative Intercalation.
AB  - Controllable bandgap widening from 1.8 to 2.6 eV is reported from oxidized MoS2
      sheets that are composed of quilted phases of various MoSxOy flakes. The
      exfoliated flakes have large size (>=100 MUm * 100 MUm) sheets with average
      thickness of 1.7 nm. Remarkably, fine reversible tuning of the bandgap is
      achieved by postprocessing sulfurization of the MoSxOy sheets.

PMID- 25867544
TI  - Risk Factors Associated With Incident Cerebral Microbleeds According to Location
      in Older People: The Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study.
AB  - IMPORTANCE: The spatial distribution of cerebral microbleeds (CMBs), which are
      asymptomatic precursors of intracerebral hemorrhage, reflects specific underlying
      microvascular abnormalities of cerebral amyloid angiopathy (lobar structures) and
      hypertensive vasculopathy (deep brain structures). Relatively little is known
      about the occurrence of and modifiable risk factors for developing CMBs,
      especially in a lobar location, in the general population of older people.
      OBJECTIVE: To investigate whether lifestyle and lipid factors predict new CMBs in
      relation to their anatomic location. DESIGN, SETTING, AND PARTICIPANTS: We
      enrolled 2635 individuals aged 66 to 93 years from the population-based Age,
      Gene/Environment Susceptibility (AGES)-Reykjavik Study in a brain imaging study.
      Participants underwent a baseline magnetic resonance imaging (MRI) examination of
      the brain from September 1, 2002, through February 28, 2006, and returned for a
      second MRI examination from April 1, 2007, through September 30, 2011. EXPOSURES:
      Lifestyle and lipid factors assessed at baseline included smoking, alcohol
      consumption, body mass index, and serum levels of total cholesterol, high- and
      low-density lipoprotein cholesterol, and triglycerides. MAIN OUTCOMES AND
      MEASURES: Incident CMBs detected on MRIs, which were further categorized as
      exclusively lobar or as deep. RESULTS: During a mean follow-up of 5.2 years, 486
      people (18.4%) developed new CMBs, of whom 308 had lobar CMBs only and 178 had
      deep CMBs. In the multivariate logarithm-binomial regression model adjusted for
      baseline cardiovascular risk factors, including blood pressure, antihypertensive
      use, prevalent CMBs, and markers of cerebral ischemic small-vessel disease, heavy
      alcohol consumption (vs light to moderate consumption; relative risk [RR], 2.94
      [95% CI, 1.23-7.01]) was associated with incident CMBs in a deep location.
      Baseline underweight (vs normal weight; RR, 2.41 [95% CI, 1.21-4.80]), current
      smoking (RR, 1.47 [95% CI, 1.11-1.94]), an elevated serum level of high-density
      lipoprotein cholesterol (RR per 1-SD increase, 1.13 [95% CI, 1.02-1.25]), and a
      decreased triglyceride level (RR per 1-SD decrease in natural logarithm
      transformed triglyceride level, 1.17 [95% CI, 1.03-1.33]) were significantly
      associated with an increased risk for lobar CMBs exclusively but not for deep
      CMBs. CONCLUSIONS AND RELEVANCE: Lifestyle and lipid risk profiles for CMBs were
      similar to those for symptomatic intracerebral hemorrhage and differed for lobar
      and deep CMBs. Modification of these risk factors could have the potential to
      prevent new-onset CMBs, particularly those occurring in a lobar location.

PMID- 25867547
TI  - Ultra-Rapid Epicardial Activation Mapping During Ventricular Tachycardia Using
      Continuous Sampling from a High-Density Basket (Orion(TM) ) Catheter.

PMID- 25867548
TI  - Rate Coefficient Determinations for H + NO2 -> OH + NO from High Pressure Flow
      Reactor Measurements.
AB  - Rate coefficients for the reaction H + NO2 -> OH + NO (R1) have been determined
      over the nominal temperature and pressure ranges of 737-882 K and 10-20 atm,
      respectively, from measurements in two different flow reactor facilities: one
      laminar and one turbulent. Considering the existing database of experimental k1
      measurements, the present conditions add measurements of k1 at previously
      unconsidered temperatures between ~820-880 K, as well as at pressures that exceed
      existing measurements by over an order of magnitude. Experimental measurements of
      NOx-perturbed H2 oxidation have been interpreted by a quasi-steady state NOx
      plateau (QSSP) method. At the QSSP conditions considered here, overall reactivity
      is sensitive only to the rates of R1 and H + O2 + M -> HO2 + M (R2.M).
      Consequently, the ratio of k1 to k2.M may be extracted as a simple algebraic
      function of measured NO2, O2, and total gas concentrations with only minimal
      complication (within measurement uncertainty) due to treatment of overall gas
      composition M that differs slightly from pure bath gas B. Absolute values of k1
      have been determined with reference to the relatively well-known, pressure
      dependent rate coefficients of R2.B for B = Ar and N2. Rate coefficients for the
      title reaction determined from present experimental interpretation of both
      laminar and turbulent flow reactor results appear to be in very good agreement
      around a representative value of 1.05 * 10(14) cm(3) mol(-1) s(-1) (1.74 * 10(
      10) cm(3) molecule(-1) s(-1)). Further, the results of this study agree both with
      existing low pressure flash photolysis k1 determinations of Ko and Fontijn (J.
      Phys. Chem. 95 3984) near 760 K as well as a present fit to the theoretical
      expression of Su et al. (J. Phys. Chem. A 106 8261). These results indicate that,
      over the temperature range considered in this study and up to at least 20 atm,
      net chemistry due to stabilization of the H-NO2 reaction intermediate to form
      isomers of HNO2 may proceed at negligible rates compared to R1. 

PMID- 25867546
TI  - Human cytomegalovirus pUL97 kinase induces global changes in the infected cell
      phosphoproteome.
AB  - Replication of human cytomegalovirus (HCMV) is regulated in part by cellular
      kinases and the single viral Ser/Thr kinase, pUL97. The virus-coded kinase
      augments the replication of HCMV by enabling nuclear egress and altering cell
      cycle progression. These roles are accomplished through direct phosphorylation of
      nuclear lamins and the retinoblastoma protein, respectively. In an effort to
      identify additional pUL97 substrates, we analyzed the phosphoproteome of SILAC
      labeled human fibroblasts during infection with either wild-type HCMV or a pUL97
      kinase-dead mutant virus. Phosphopeptides were enriched over a titanium dioxide
      matrix and analyzed by high-resolution MS. We identified 157 unambiguous
      phosphosites from 106 cellular and 17 viral proteins whose phosphorylation
      required UL97. Analysis of peptides containing these sites allowed the
      identification of several candidate pUL97 phosphorylation motifs, including a
      completely novel phosphorylation motif, LxSP. Substrates harboring the LxSP motif
      were enriched in nucleocytoplasmic transport functions, including a number of
      components of the nuclear pore complex. These results extend the known functions
      of pUL97 and suggest that modulation of nuclear pore function may be important
      during HCMV replication. 

PMID- 25867549
TI  - Diffusion MRI abnormalities detection with orientation distribution functions: a
      multiple sclerosis longitudinal study.
AB  - We propose a new algorithm for the voxelwise analysis of orientation distribution
      functions between one image and a group of reference images. It relies on a
      generic framework for the comparison of diffusion probabilities on the sphere,
      sampled from the underlying models. We demonstrate that this method, combined to
      dimensionality reduction through a principal component analysis, allows for more
      robust detection of lesions on simulated data when compared to classical tensor
      based analysis. We then demonstrate the efficiency of this pipeline on the
      longitudinal comparison of multiple sclerosis patients at an early stage of the
      disease: right after their first clinically isolated syndrome (CIS) and three
      months later. We demonstrate the predictive value of ODF-based scores for the
      early detection of lesions that will appear or heal. 

PMID- 25867550
TI  - Negative affect variability and adolescent self-medication: The role of the peer
      context.
AB  - INTRODUCTION: Findings in the literature show mixed support for adolescent self
      medication. Following recent reformulations of the self-medication hypothesis, we
      tested within-person effects of daily fluctuations in sadness and worry on daily
      substance use, and explored the moderating role of the peer context on self
      medication. We hypothesized that greater daily fluctuations in mood would predict
      greater daily substance use, and lower levels of peer social support and higher
      levels of peer drug use would further increase this risk. DESIGN AND METHODS:
      Experience sampling methods captured within-person daily variations in mood and
      substance use over 21 days among 73 adolescents. An observational coding system
      was employed to characterize enacted peer social support. Multilevel modeling was
      used to parse between- versus within-person differences in risk for daily
      substance use. RESULTS: Greater within-person daily fluctuations in feelings of
      worry (but not sadness) significantly predicted increased daily substance use,
      consistent with self-medication. Moreover, greater daily fluctuations in negative
      affect were a stronger predictor of daily use than total level of daily negative
      affect. Peer social support moderated this relationship such that those with more
      supportive friendships were less likely to engage in self-medication. DISCUSSION:
      This is the first reported study to examine within-person processes of adolescent
      self-medication related to daily variability in mood and the peer context.
      Adolescent self-medication processes appear to differ depending on the type of
      negative affect and whether daily affective experiences are chronic or
      fluctuating, suggesting that the affective processes that cue adolescents to
      engage in substance use are quite nuanced.

PMID- 25867551
TI  - A simple critical-sized femoral defect model in mice.
AB  - While bone has a remarkable capacity for regeneration, serious bone trauma often
      results in damage that does not properly heal. In fact, one tenth of all limb
      bone fractures fail to heal completely due to the extent of the trauma, disease,
      or age of the patient. Our ability to improve bone regenerative strategies is
      critically dependent on the ability to mimic serious bone trauma in test animals,
      but the generation and stabilization of large bone lesions is technically
      challenging. In most cases, serious long bone trauma is mimicked experimentally
      by establishing a defect that will not naturally heal. This is achieved by
      complete removal of a bone segment that is larger than 1.5 times the diameter of
      the bone cross-section. The bone is then stabilized with a metal implant to
      maintain proper orientation of the fracture edges and allow for mobility. Due to
      their small size and the fragility of their long bones, establishment of such
      lesions in mice are beyond the capabilities of most research groups. As such,
      long bone defect models are confined to rats and larger animals. Nevertheless,
      mice afford significant research advantages in that they can be genetically
      modified and bred as immune-compromised strains that do not reject human cells
      and tissue. Herein, we demonstrate a technique that facilitates the generation of
      a segmental defect in mouse femora using standard laboratory and veterinary
      equipment. With practice, fabrication of the fixation device and surgical
      implantation is feasible for the majority of trained veterinarians and animal
      research personnel. Using example data, we also provide methodologies for the
      quantitative analysis of bone healing for the model. 

PMID- 25867552
TI  - Do spouses matter? Discrimination, social support, and psychological distress
      among Asian Americans.
AB  - OBJECTIVE: Perceived discrimination poses risks for psychological distress among
      Asian Americans, but the differential impact of general unfair treatment and
      racial discrimination has not been examined. Although social support from distal
      sources reduces discrimination-related distress either directly or as a buffer,
      the unique roles of spousal support have remained understudied. Nativity status
      was examined as another moderator of these relationships to resolve previous
      inconsistent findings regarding its relationship to the discrimination-distress
      link. METHOD: Data were from 1,626 U.S.- and foreign-born Asian American adults
      (Mage = 42.17 years; n = 1,142 married/cohabiting) in the nationally
      representative National Latino and Asian American Study, who reported on
      experiences of unfair treatment, racial discrimination, social supports from
      spouses, family, friends, and neighborhood, and psychological distress. RESULTS:
      Hierarchical multiple regressions showed that both unfair treatment and racial
      discrimination predicted psychological distress, and spousal support predicted
      distress above and beyond distal forms of social support in the context of
      perceived discrimination. Moderation analyses revealed that spousal support
      buffered against negative psychological consequences of unfair treatment, but not
      racial discrimination. Spousal support was not differentially protective as a
      function of nativity; however, U.S.-born respondents reacted with greater
      distress to unfair treatment than their foreign-born counterparts. CONCLUSIONS:
      Psychological effects of both general and race-based discrimination, and the
      unique contributions of distinct sources of social support, are important to
      understanding adjustment and cultural transition among Asian Americans. Nativity
      differentially influences effects of unfair treatment. Implications for future
      research are discussed.

PMID- 25867553
TI  - Electron spin resonance scanning probe spectroscopy for ultrasensitive
      biochemical studies.
AB  - Electron spin resonance (ESR) spectroscopy's affinity for detecting paramagnetic
      free radicals, or spins, has been increasingly employed to examine a large
      variety of biochemical interactions. Such paramagnetic species are broadly found
      in nature and can be intrinsic (defects in solid-state materials systems,
      electron/hole pairs, stable radicals in proteins) or, more often, purposefully
      introduced into the material of interest (doping/attachment of paramagnetic spin
      labels to biomolecules of interest). Using ESR to trace the reactionary path of
      paramagnetic spins or spin-active proxy molecules provides detailed information
      about the reaction's transient species and the label's local environment. For
      many biochemical systems, like those involving membrane proteins, synthesizing
      the necessary quantity of spin-labeled biomolecules (typically 50 pmol to 100
      pmol) is quite challenging and often limits the possible biochemical reactions
      available for investigation. Quite simply, ESR is too insensitive. Here, we
      demonstrate an innovative approach that greatly enhances ESR's sensitivity
      (>20000* improvement) by developing a near-field, nonresonant, X-band ESR
      spectrometric method. Sensitivity improvement is confirmed via measurement of 140
      amol of the most common nitroxide spin label in a ~593 fL liquid cell at ambient
      temperature and pressure. This experimental approach eliminates many of the
      typical ESR sample restrictions imposed by conventional resonator-based ESR
      detection and renders the technique feasible for spatially resolved measurements
      on a wider variety of biochemical samples. Thus, our approach broadens the pool
      of possible biochemical and structural biology studies, as well as greatly
      enhances the analytical power of existing ESR applications. 

PMID- 25867554
TI  - Exploration of the Genetic Epidemiology of Asthma: A Review, with a Focus on
      Prevalence in Children and Adolescents in the Caribbean.
AB  - Asthma is a chronic disease caused by the inflammation of the main air passages
      of the lungs. This paper outlines a review of the published literature on asthma.
      While a few studies show a trend of rising asthma cases in the Caribbean region,
      even fewer have explored the genetic epidemiological factors of asthma. This is a
      literature review that seeks to sum the body of knowledge on the epidemiology of
      asthma. Specifically, the major objective of the literature review is to provide
      a unified information base on the current state of factors involved in the
      genetic epidemiology of asthma. The review is a simple, yet detailed summary of
      the literature sources and their methodology and findings on the genetic
      epidemiology of asthma. Further, it seeks to direct this effort to the Caribbean
      region. The paper then reviews a summarized and synthesized collection of the
      body of previous research. Of specific interest are peer-reviewed sources that
      have been published in recent times. The paper provides more recent insight and
      recapitulates on the previous research, while tracing the intellectual progress
      on the debate. Where possible, reviewing and discussing the results of the
      previous literature, this review singles out the gaps and potential future
      research directions for studying the genetic epidemiology of asthma. Overall, we
      hope to contribute to a more synthesized knowledge and improved understanding of
      the previous literature and future potential direction of genetic and
      epidemiological asthma research. 

PMID- 25867555
TI  - The Incidence of Cardiac Lesions among Children with Down's Syndrome in Jamaica -
      A Prospective Study.
AB  - OBJECTIVES: This study aimed to define the incidence of Down's syndrome and to
      describe the epidemiology of cardiac lesions in Jamaican children with Down's
      syndrome. METHODS: A prospective study was conducted on 53 infants during the
      period January 1, 2007 to December 31, 2007, at the Bustamante Hospital for
      Children, Kingston, Jamaica. A medical history, physical examination and echo
      Doppler was performed on each child. RESULTS: Forty-six thousand babies were born
      in Jamaica in 2007, of which 53 infants were diagnosed with Down's syndrome,
      giving an incidence of 1:868. Forty-two (79.2%) infants had congenital heart
      lesions. Of the 42 patients with cardiac lesions, 50% had an isolated cardiac
      lesion while 50% had multiple defects. The most common single defect was the
      atrioventricular septal defect found in 10 (24%) patients. The most frequent
      concomitant malformation was a patent ductus arteriosus, found in 16 (38.1%) of
      the patients. The median age of diagnosis with Down's syndrome was 0.14 weeks
      (interquartile range (IQR) 0 to 68 weeks). The median age of diagnosis with the
      cardiac lesion was 15.1 weeks (IQR 0 to 40.0 weeks). CONCLUSIONS: The incidence
      of Down's syndrome in Jamaica is similar to the reported international
      experience. The distribution of cardiac malformations is similar to other
      countries; however, the main difference is the higher incidence of congenital
      heart disease and a higher incidence of combined lesions.

PMID- 25867556
TI  - Comparison of Cerebral Oximeter and Pulse Oximeter Values in the First 72 Hours
      in Premature, Asphyctic and Healthy Newborns.
AB  - AIM: The monitoring of oxygenation is essential for providing patient safety and
      optimal results. We aimed to determine brain oxygen saturation values in healthy,
      asphyctic and premature newborns and to compare cerebral oximeter and pulse
      oximeter values in the first 72 hours of life in neonatal intensive care units.
      METHODS: This study was conducted at the neonatal intensive care unit (NICU) of
      Van Yuzuncu Yil University Research and Administration Hospital. Seventy-five
      neonatal infants were included in the study (28 asphyxia, 24 premature and 23
      mature healthy infants for control group). All infants were studied within the
      first 72 hours of life. We used a Somanetics 5100C cerebral oximeter (INVOS
      cerebral/somatic oximeter, Troy, MI, USA). The oxygen saturation information was
      collected by a Nellcor N-560 pulse oximeter (Nellcor-Puriton Bennet Inc,
      Pleasanton, CA, USA). RESULTS: In the asphyxia group, the cerebral oximeter
      average was 76.85 +/- 14.1, the pulse oximeter average was 91.86 +/- 5.9 and the
      heart rate average was 139.91 +/- 22.3. Among the premature group, the cerebral
      oximeter average was 79.08 +/- 9.04, the pulse oximeter average was 92.01 +/- 5.3
      and the heart rate average was 135.35 +/- 17.03. In the control group, the
      cerebral oximeter average was 77.56 +/- 7.6, the pulse oximeter average was 92.82
      +/- 3.8 and the heart rate average was 127.04 +/- 19.7. CONCLUSION: Cerebral
      oximeter is a promising modality in bedside monitoring in neonatal intensive care
      units. It is complementary to pulse oximeter. It may be used routinely in
      neonatal intensive care units.

PMID- 25867557
TI  - Systems for Paediatric Sepsis: A Global Survey.
AB  - OBJECTIVES: To evaluate the resources available for early diagnosis and treatment
      of paediatric sepsis at hospitals in developing and developed countries. METHODS:
      This was a voluntary online survey involving 101 hospitals from 41 countries
      solicited through the World Federation of Pediatric Intensive and Critical Care
      Societies contact list and website. The survey was designed to assess the
      spectrum of sepsis epidemiology, patterns of applied therapies, availability of
      resources and barriers to optimal sepsis treatment. RESULTS: Ninety per cent of
      respondents represented a tertiary or general hospital with paediatric intensive
      care facilities, including 63% from developed countries. Adequate triage services
      were absent in more than 20% of centres. Insufficiently trained personnel and
      lack of a sepsis protocol was reported in 40% of all sites. While there were
      specific guidelines for sepsis management in 78% of centres (n = 100), protocols
      for assessing sepsis patients were not applied in nearly 70% of centres. Lack of
      parental recognition of sepsis and failure of referring centres to diagnose
      sepsis were identified as major barriers by more than 50% of respondents.
      CONCLUSIONS: Even among centres with no significant resource constraints and
      advanced medical systems, significant deficits in sepsis care exist. Early
      recognition and management remain a key issue and may be addressed through
      improved triage, augmented support for referring centres and public awareness.
      Focussed research is necessary at the institutional level to identify and address
      specific barriers.

PMID- 25867558
TI  - Cutaneous Malignant Melanoma in Jamaica, 1958 to 2007.
AB  - OBJECTIVE: To document the epidemiology of cutaneous malignant melanoma (CMM) in
      Jamaica over the 50-year period, 1958-2007. METHODS: All cases of CMM recorded in
      the Jamaica Cancer Registry (JCR), for the period 1958-2007, were collected. For
      each case, we documented method of ascertainment, age, gender and anatomical
      location. Age standardized incidence rates (ASRs) for the seven five-year periods
      from 1973-2007 were also obtained from the JCR. RESULTS: There were 220 cases of
      CMM from 218 patients (131 females, 87 males; male:female ratio 1:1.5), ranging
      in age from 21 to 98 years (median age 62 years). The majority of cases (94%)
      were ascertained via biopsy. The ASRs fluctuated around 0.9 per 100 000 per year
      from 1973 to 2007, ranging from 0.6-1.4 per 100 000 per year in females and 0.5
      1.1 per 100 000 per year in males. Cutaneous malignant melanoma was most common
      in the lower limb (59% of males and 69% of females). The foot was the most common
      lower limb site (female: 77%, male: 83%) and the commonest site overall (female:
      53%, male: 49%). CONCLUSION: In Jamaica, CMM is more common in females than in
      males. In both genders, the ASRs were noted to be low and fluctuated around 0.9
      per 100 000 per year since 1973. The lower limb is the commonest anatomical site,
      with the majority of cases involving the foot. These findings are similar to
      those documented in other predominantly Black populations.

PMID- 25867559
TI  - Physicians' Knowledge of Cardiopulmonary Resuscitation Guidelines and Current
      Certification Status at the University Hospital of the West Indies, Jamaica.
AB  - OBJECTIVE: To determine physicians' knowledge of cardiopulmonary resuscitation
      (CPR) guidelines at the University Hospital of the West Indies (UHWI), Jamaica,
      and their current certification status in basic life support (BLS), advanced
      cardiac life support (ACLS), paediatric advanced life support (PALS) and advanced
      trauma life support (ATLS). METHODS: This was a cross-sectional study. A 23-item
      self-administered questionnaire was used to assess physicians practising at the
      UHWI, from the Departments of Anaesthesia, Surgery, Internal Medicine, Accident
      and Emergency, Obstetrics and Gynaecology and Oncology. RESULTS: One hundred and
      forty-three (65%) of the targeted 220 physicians responded. There were 77 (55%)
      females and 41% of respondents were between ages 26 and 30 years. Knowledge of
      CPR guidelines was inadequate, as the median score obtained was 4.0
      (interquartile range [IQR] 2-5) out of a possible eight. Physician seniority was
      inversely related to knowledge scores (p < 0.01). While 86% of all respondent
      physicians had been trained in BLS, only 46% were certified at the time of the
      study. Fewer (52%) were trained in ACLS with only 36% currently certified. Only
      65% had been trained in the use of a defibrillator. Most knew the correct
      compression rate (78%), but only 46% knew the compressions to breaths ratio for
      both single and two-rescuer CPR. Only 42% of anaesthetists and 27% of emergency
      physicians were currently ACLS certified. CONCLUSION: Physician knowledge of CPR
      protocols was suboptimal and current certification levels were low. Increased
      training and recertification is necessary to improve physician knowledge which is
      expected to result in improved performance of CPR.

PMID- 25867560
TI  - 3Ps--Pharmacist, Physician and Patient: Proposal for Joint Cooperation to
      Increase Adherence to Medication.
AB  - OBJECTIVE: Older people receive medications for chronic diseases and therefore
      adherence is an important health and economic concern. The objective of the study
      is to determine relationships between pharmacist, patient and patient's family
      physician with special emphasis on the comparison of adherent and non-adherent
      patients. METHODS: The study was designed as a cross-sectional survey by use of a
      self-administered 33-item questionnaire. The study included 635 individuals
      collecting or buying drugs for the treatment of chronic diseases and 84
      pharmacists dispensing drugs for chronic diseases to patients. RESULTS: The study
      included 265 (41.7%) adherent and 370 (58.3%) non-adherent patients. Comparison
      of particular answers between patients and pharmacists revealed a discrepancy,
      with a significant difference in five of eight answers. The highest difference
      was recorded in answers to the question whether a pharmacist offered thorough
      advice to the patient on how to take the drug; an affirmative answer to this
      question was given by 90.5% of pharmacists and only 57.2% of patients. The
      analysis of respondents' claims about their relation with one doctor shows that
      in the first place, with the highest number of positive responses, is the claim
      of the respondents that their doctor always explains the results of laboratory
      tests and other specialized findings (n = 489, 77.0%). CONCLUSION: Enhancing
      communication between the physician, the pharmacist and the patient is a key in
      boosting the patient's ability to follow a medication regimen. Pharmacist
      physician-patient relationship can improve adherence to medication. It is very
      important to empower pharmacists to offer and allow time for patient counselling.

PMID- 25867561
TI  - Sociodemographic, Socio-economic, Clinical and Behavioural Factors Modifying
      Experience and Prevalence of Dental Caries in the Permanent Dentition.
AB  - OBJECTIVE: To identify the sociodemographic, socio-economic, clinical and
      behavioural factors that modify the experience of decayed, missing and filled
      teeth (DMFT) and caries prevalence in Nicaraguan children 9-12 years old.
      SUBJECTS AND METHODS: We conducted a cross-sectional study in 800 school children
      9-12 years old in the city of Leon, Nicaragua. The clinical oral examinations to
      identify caries experience were undertaken by two trained and certified
      examiners. Sociodemographic, socio-economic and behavioural data were collected
      using questionnaires. Negative binomial regression (NBR) and binary logistic
      regression (BLR) models were used to model caries experience and caries
      prevalence, respectively. RESULTS: Mean DMFT index was 0.98 +/- 1.74 and caries
      prevalence (DMFT > 0) was 37.9%. In the NBR model, the categories that increase
      the expected DMFT mean were: older age, female gender, presence of plaque, and if
      the school children received curative and curative/preventive dental care in the
      last year. In the BLR model, the odds of presenting with caries in the permanent
      dentition were increased in older children, those from large families, mothers
      with a positive dental attitude, and those school children who received curative
      and curative/preventive dental care in the last year. CONCLUSIONS: Using
      different models, we identified several sociodemographic, socio-economic,
      clinical and behavioural factors that modify the experience (NBR) and prevalence
      (BLR) of dental caries.

PMID- 25867562
TI  - Salivary Parameters (Salivary Flow, pH and Buffering Capacity) in Stimulated
      Saliva of Mexican Elders 60 Years Old and Older.
AB  - OBJECTIVE: To compare a limited array of chewing-stimulated saliva features
      (salivary flow, pH and buffer capacity) in a sample of elderly Mexicans with
      clinical, sociodemographic and socio-economic variables. SUBJECTS AND METHODS: A
      cross-sectional study was carried out in 139 adults, 60 years old and older, from
      two retirement homes and a senior day care centre in the city of Pachuca, Mexico.
      Sociodemographic, socio-economic and behavioural variables were collected through
      a questionnaire. A trained and standardized examiner obtained the oral clinical
      variables. Chewing-stimulated saliva (paraffin method) was collected and the
      salivary flow rate, pH and buffer capacity were measured. The analysis was
      performed using non-parametric tests in Stata 9.0. RESULTS: Mean age was 79.1 +/-
      9.8 years. Most of the subjects included were women (69.1%). Mean chewing
      stimulated salivary flow was 0.75 +/- 0.80 mL/minute, and the pH and buffer
      capacity were 7.88 +/- 0.83 and 4.20 +/- 1.24, respectively. Mean chewing
      stimulated salivary flow varied (p < 0.05) across type of retirement home, tooth
      brushing frequency, number of missing teeth and use of dental prostheses. pH
      varied across the type of retirement home (p < 0.05) and marginally by age (p =
      0.087); buffer capacity (p < 0.05) varied across type of retirement home, tobacco
      consumption and the number of missing teeth. CONCLUSIONS: These exploratory data
      add to the body of knowledge with regard to chewing-stimulated salivary features
      (salivary flow rate, pH and buffer capacity) and outline the variability of those
      features across selected sociodemographic, socio-economic and behavioural
      variables in a group of Mexican elders.

PMID- 25867563
TI  - Cancer Treatment: The Cost Factor.
AB  - Countries in the Caribbean region have expressed concern at the rising incidence
      of chronic non-communicable diseases. Cancer is one of these and the cost of
      treating patients with this has escalated in the recent past. In this paper, the
      author examines colon cancer and the cost of caring for patients with this. A
      viewpoint with regard to the reasons for the increased cost of care of patients
      with cancer is advanced. The factors contributing to the increasing costs are
      explored. Research epistemology and the role of the pharmaceutical industry are
      also explored. The need for consensus decision-making with regard to choice of
      agent/regime is emphasized, as is the need for a deliberate cost-benefit
      approach. 

PMID- 25867564
TI  - Conservative Management of Keratocystic Odontogenic Tumour with Enucleation,
      Excision of the Overlying Mucosa and Electrocauterization - A Case Report.
AB  - Odontogenic keratocyst remains an enigma for clinicians and researchers, although
      gains in knowledge in recent years have improved the understanding of this
      interesting lesion. The diagnostic problems are mainly related to the relative
      lack of specific clinical and radiographic features that unequivocally point to a
      proper diagnosis. Of particular interest to clinicians is the biologic behaviour
      of keratocysts which includes high rates of recurrence and potential existence as
      a benign odontogenic neoplasm, keratocystic odontogenic tumour. Various surgical
      modalities have evolved in an attempt to reduce the recurrence rate, including
      curettage, peripheral ostectomy, removal of overlying mucosa in cases of cortical
      perforation and osseous resection in the form of marginal or segmental
      osteotomies. The present case report describes the conservative surgical
      management of a large keratocystic odontogenic tumour in a young patient with no
      evidence of recurrence at two years follow-up. 

PMID- 25867565
TI  - A Simplified HAART Regimen with Raltegravir and Lamivudine, and Pharmacokinetic
      Interactions with a Combined Immunosuppressive Therapy with Tacrolimus and
      Everolimus in an HIV/HCV/HBV/HDV Patient after Liver Transplantation.
AB  - In this case report, we examine the impact of a simplified two-drug highly active
      antiretroviral therapy (HAART) regimen of raltegravir and lamivudine in a patient
      co-infected with human immunodeficiency virus (HIV) and hepatitis C, D and B
      viruses (HCV/HDV/HBV) under immunosuppressive therapy after liver
      transplantation. Pharmacokinetic interactions between integrase inhibitors and
      immunosuppressant drugs are described. Raltegravir, the first integrase
      inhibitor, associated with lamivudine, was introduced because its metabolism does
      not interfere with immunosuppressant therapy. During post-orthotopic liver
      transplantation follow-up, the patient's transaminases level increased and his
      antiretroviral therapy (HAART) of tenofovir/emtricitabine and fosamprenavir was
      changed, due to suspected drug toxicity. After seven months of follow-up, the
      patient showed good tolerance, good viro-immunological control with undetectable
      HIV viraemia and stable concentrations of immunosuppressive drugs. This case
      indicates that the combination of raltegravir and lamivudine is an optimal and
      effective strategy because it resulted in an important reduction of hepatic
      transaminases in a patient with very critical clinical conditions. 

PMID- 25867566
TI  - Long-term Maraviroc Therapy and Limited Side Effects in an HIV-1 Experienced
      Patient: Six Years of Antiretroviral Observation.

PMID- 25867567
TI  - A Case of Tuberculous Meningitis with Atypical Multiple Lesions.
AB  - This case describes a rare case of tuberculous meningitis. A 50-year old female
      presented with seven days of numbness on the left side, fatigue and a three-day
      headache. Magnetic resonance imaging (MRI) showed multiple lesions in the dorsal
      medulla and upper cervical spinal. After admission, she developed a long-term
      fever, cranial nerves palsy and showed little response to corticosteroid,
      antibacterial and antiviral therapy. She received a diagnostic anti-tuberculous
      therapy (ATT); despite that, all examinations for tuberculosis were negative.
      After ATT lasting 16 days, she recovered and was discharged from hospital with
      slight asthenia and hypoesthesia. 

PMID- 25867568
TI  - Three Overlapping Balloon-expandable Stents Applied in Coeliac Artery Dissection:
      Case Report and Literature Review.

PMID- 25867569
TI  - Compound Odontoma: Differential Diagnosis and Review of the Literature.
AB  - Odontomas are the most common odontogenic tumours. They are usually asymptomatic
      and are often discovered during routine radiography. Compound odontomas are
      regularly calcified tissue that bear similarity to teeth or appear as a
      collection of small teeth. We report a rare case of compound odontoma in the
      mandible of an adult patient with clinical and radiological features and a review
      of the literature. 

PMID- 25867570
TI  - Multiple Lesions in the Upper Jaw.
AB  - Buccal exostoses are benign, broad-based surface masses of the outer or facial
      aspect of the upper jaw (maxilla) or, less commonly, the lower jaw (mandible).
      They begin to develop in early adulthood and may very slowly enlarge over years.
      We report here an adult man with multiple masses of the maxilla above the teeth. 

PMID- 25867571
TI  - Lisch and the Importance of His Nodules.
AB  - Neurofibromatosis 1 is the commonest neurocutaneous autosomal dominant disorder
      with full penetrance, although expression may not be complete by the age of five
      years. Lisch nodules, however, are predominantly visible in children usually
      after the age of six years. Therefore, it is important to appreciate that their
      absence before this age does not pre-empt the diagnosis. A child being treated
      for hypertension of unknown aetiology with cafe au lait lesions presented to the
      ophthalmologist with blurred vision. Clinical examination revealed Lisch nodules
      which confirmed the suspicion of neurofibromatosis 1 as per National Institutes
      of Health criteria. The aim of this report is to highlight the importance of
      regular ophthalmic screening, both in suspected and confirmed cases, as these
      patients have long-term sequelae. 

PMID- 25867572
TI  - Potentiation of Endocrine Adverse Effects of Lithium by Enalapril and Verapamil.
AB  - Lithium, which is widely used in the management of patients with bipolar
      disorder, may alter the function of some endocrine organs, particularly the
      thyroid and parathyroid glands, as well as it may reduce the sensitivity of the
      kidneys to vasopressin. In most lithium-treated patients, endocrine abnormalities
      are limited to one endocrine organ and are observed only after long-term lithium
      therapy. The patient reported in this study developed hypothyroidism,
      hyperparathyroidism and nephrogenic diabetes insipidus. However, the last two
      disorders were induced by a small increase in plasma lithium levels as a result
      of the treatment with enalapril and verapamil. This case shows that patients at
      high risk of thyroid, parathyroid or renal disorders receiving lithium should not
      be treated with drugs known to interfere with plasma lithium levels. 

PMID- 25867573
TI  - Bleomycin-induced Flagellate Erythema: A Rare and Unique Drug Rash.
AB  - Bleomycin-induced flagellate erythema is a rare rash associated with the use of
      the drug. The rash has a characteristic and intermingled lacy appearance as if it
      has been whipped. Lack of detoxifying enzymes for bleomycin in the skin makes it
      a vulnerable site for the adverse effects of bleomycin, along with the lungs. We
      report the case of young girl with germ cell tumour who developed bleomycin
      induced flagellate erythema. 

PMID- 25867574
TI  - Is the Incidence of Thyroid Cancer Increasing in Medical Staff?

PMID- 25867575
TI  - Dural Venous Sinus Thrombosis in Sickle Cell Disease in a West Indian.

PMID- 25867576
TI  - Right Ovarian Mucinous Cystadenoma Coexisting with an Incidental Left Ovarian
      Haemangioma in a Postmenopausal Patient.

PMID- 25867577
TI  - Can Chronic Consumption of Noni (Morinda citrifolia) Juice Lead to Changes in the
      Coagulation Profile, Deranged Liver Function and Excessive Intraoperative
      Haemorrhage?

PMID- 25867578
TI  - Clinical Factors Associated with Morbidity and Mortality in Patients Admitted
      with Sickle Cell Disease.
AB  - OBJECTIVE: To determine the clinical factors associated with the length of
      hospitalization and mortality in patients with sickle cell disease (SCD).
      METHODS: All patients with SCD admitted to the medical wards of the University
      Hospital of the West Indies, Jamaica, over a five-year period, January 1 to
      December 31, 2010, were reviewed. Data were extracted from hospital charts and
      comprised demographic and clinical information, investigations, interventions,
      duration of stay, pathological data and outcomes. RESULTS: There were 105
      patients reviewed; 84% were genotype Hb SS. Females accounted for 59% and males
      41%. Overall mean age was 32.5 years (SD 13.7, range 12-66 years). The mean
      length of hospitalization was 10.2 days (SD 10.9, range 1-84 days). The main
      admission diagnoses were painful crisis, acute chest syndrome, severe anaemia,
      sepsis, hepatic sequestration, congestive cardiac failure and renal failure. The
      mean value for the following laboratory investigations were: haemoglobin 7.7 g/dL
      (SD 2.8), total white blood cell count 21.7 x 109/L (SD 14.2), platelet count 320
      x 109/L (SD 191.9), blood urea 9.8 mmol/L (SD 11.9) and serum creatinine 198
      umol/L (SD 267.9). Medical interventions included: blood transfusions in 20.9%,
      55% received antibiotics and 74% received narcotic analgesia. There were 40
      deaths with four autopsies done. The mortality rate for SCD was 38%. There were
      189 repeat SCD admissions. CONCLUSION: Sickle cell disease still carries a high
      morbidity and mortality in patients admitted to hospital. Recurrent admissions
      are a concern, as they impact on patient's morbidity and quality of life.

PMID- 25867579
TI  - Effects of Preoperative Clarithromycin Administration in Patients with Nasal
      Polyposis.
AB  - OBJECTIVE: In recent years, various investigators have shown considerable
      interest in the use of macrolide antibiotics for treatment of chronic
      rhinosinusitis and nasal polyposis. The aim of this study was to evaluate the
      clinical effects of preoperative long-term, low-dose clarithromycin
      administration in patients with nasal polyposis. METHODS: Eighty nasal polyp
      patients (42 non-atopic and 38 atopic) were included in this prospective, non
      placebo controlled investigation and randomized equally to either the combined
      clarithromycin-surgical or surgical group. Forty patients received 500 mg of
      clarithromycin daily for eight weeks, and, after evaluation, they were treated by
      functional endoscopic sinus surgery (FESS). The other 40 patients were treated
      only surgically. The nasal symptom scores and endoscopic scores after macrolide
      treatment/surgical treatment, and after six and 12 months of follow-up were
      evaluated. RESULTS: After clarithromycin therapy, we found improvement in symptom
      scores in 25/40, and improvement in endoscopic scores in 19/40 patients. We found
      no significant difference in nasal symptom score between allergic and non
      allergic patients regarding the outcome to macrolide (p = 0.352) or surgical
      treatment (p = 0.396). When we compared differences between endoscopic scores at
      the time points of 12 months and six months postoperatively (ESt12 minus ESt6),
      we found statistically lower differences in the clarithromycin-surgery group than
      in the surgery group (p = 0.006). CONCLUSION: Preoperative clarithromycin
      administration postponed nasal polyp relapse after FESS. Allergies have no
      influence on the clinical efficacy of clarithromycin therapy and on the efficacy
      of FESS.

PMID- 25867580
TI  - Ultrasonographic Measurement of the Femoral Cartilage Thickness in Patients with
      Behcet's Disease.
AB  - OBJECTIVE: To evaluate femoral cartilage thickness in patients with Behcet's
      disease (BD) by using ultrasonography. METHODS: Thirty-one patients with BD (18
      M, 13 F; mean age: 32.87 +/- 8.5 years) and 31 age-, gender- and body mass index
      matched healthy subjects were enrolled. Demographic features and medications of
      the patients were recorded. The femoral cartilage thicknesses of both knees were
      measured with a 7-12 MHz linear probe while subjects' knees were held in maximum
      flexion. Three mid-point measurements were taken from both knees: lateral femoral
      condyle (LFC), intercondylar area (ICA) and medial femoral condyle (MFC).
      RESULTS: Cartilage measurements of BD patients were significantly thinner at the
      ICA (p = 0.009) and LFC (p = 0.007) on the left knee, and at the MFC on both
      sides (both p < 0.05). Left knee cartilage thickness value at MFC (p = 0.005) was
      decreased in BD patients with arthritis compared to the healthy control group.
      CONCLUSION: These preliminary findings of decreased femoral cartilage thickness
      in BD patients with arthritis should be complemented with future studies.
      However, the possibility of early knee joint degeneration and eventual
      osteoarthritis in BD should also be kept in mind.

PMID- 25867581
TI  - Satisfaction Level of New Mothers with Prenatal Care and the Healthcare
      Professionals Who Provide It.
AB  - INTRODUCTION: Prenatal care is a key strategy to reduce maternal mortality. The
      aims of this work were to ascertain the level of satisfaction of new mothers with
      their pregnancy monitoring and with the medical professionals who provided
      prenatal care. SUBJECTS AND METHODS: A descriptive study was conducted on 265 new
      mothers, 18-43 years of age, who had given birth at the Virgen de las Nieves
      University Hospital and the San Cecilio University Hospital in Granada (Spain) in
      April and May 2012. The data were collected with a questionnaire consisting of 28
      items that elicited information from the subjects about their pregnancy, prenatal
      care activities, the healthcare professionals that provided the care, and those
      that they would like to monitor future pregnancies. There were also two open
      questions. The first was about the perceived needs of the participants and the
      second asked them to suggest ways that prenatal care could be improved. RESULTS:
      The majority of the subjects (59.6%) had given birth for the first time. The
      midwife was the healthcare professional who performed most of the monitoring
      activities and resolved their doubts and problems (32.74%), gave the subjects
      tranquility and security (37.86%) and listened to their worries (34.53%). The
      subjects' satisfaction with the healthcare professionals was generally high. This
      was particularly true of the midwife (90.75%). Half of the subjects surveyed said
      that they wanted the midwife, obstetrician and general practitioner to monitor
      their pregnancy. They also underlined the need for longer and more visits with
      the midwife as well as more consultations with the obstetrician and higher number
      of ultrasounds. CONCLUSIONS: The subjects were very satisfied with the work of
      the healthcare professionals that monitored their pregnancy, particularly with
      the midwife. However, they also highlighted expectations and needs that, if met,
      would increase their satisfaction.

PMID- 25867582
TI  - A Review of Pharmacovigilance.
AB  - Pharmacovigilance supports safe and appropriate use of drugs. Spontaneous
      reporting of adverse drug reactions (ADRs) is an essential component of
      pharmacovigilance. However, there is significant underreporting of ADRs. Adverse
      drug reactions have become a major problem in developing countries. Knowledge of
      pharmacovigilance could form the basis for interventions aimed at improving
      reporting rates and decreasing ADRs. 

PMID- 25867584
TI  - Copper-induced hydrogen peroxide upregulation of a metallothionein gene, OsMT2c,
      from Oryza sativa L. confers copper tolerance in Arabidopsis thaliana.
AB  - Metallothioneins (MTs) are low-molecular-weight, cysteine-rich metal-binding
      proteins found in numerous genera and species, but their functions in abiotic
      stress tolerance remain unclear. Here, a MT gene from Oryza sativa, OsMT2c, was
      isolated and characterized, encoding a type 2 MT, and observed expression in the
      roots, leaf sheathes, and leaves, but only weak expression in seeds. OsMT2c was
      upregulated by copper (Cu) and hydrogen peroxide (H2O2) treatments. Excessive Cu
      elicited a rapid and sustained production and release of H2O2 in rice, and
      exogenous H2O2 scavengers N,N'-dimethylthiourea (DMTU) and ascorbic acid (Asc)
      decreased H2O2 production and OsMT2c expression. Furthermore, the expression of
      OsMT2c increased in the osapx2 mutant in which the H2O2 levels were higher than
      in wild-type (WT) plants. These results showed that Cu increased MT2c expression
      through the production and accumulation of Cu-induced H2O2 in O. sativa. In
      addition, the transgenic OsMT2c-overexpressing Arabidopsis displayed improved
      tolerance to Cu stress and exhibited increased reactive oxygen species (ROS)
      scavenging ability compared to WT and empty-vector (Ev) seedlings. 

PMID- 25867583
TI  - Clonogenically Culturing and Expanding CD34+ Liver Cancer Stem Cells in Vitro.
AB  - A large number of cancer stem cells (CSCs) have been isolated and identified;
      however, none has been cultured in an unlimited manner in vitro without losing
      tumorigenicity and multipotency. In this study, we successfully clonogenically
      cultured a newly identified CD34+ liver CSC (LCSC) on feeder cells up to 22
      passages (to date) without losing CSC property. Cloned CD34+ LCSC formed a round
      packed morphology and it could also be cryopreserved and recultured. Stem cell
      markers, CD34, CD117, and SOX2; normal liver stem cell markers, alpha
      fetoprotein, CK19, CK18, and OV6; putative CSC markers, CD44, CD133, EpCAM, and
      CD90; as well as CD31 were expressed in cloned CD34+ LCSC. SOX2 was the major
      factor in maintaining this LCSC before colonization, and interestingly, OCT4,
      SOX2, NAONG, Klf4, c-Myc, and Lin28 were upregulated in association with
      symmetric self-renewal for colony growth of CD34+ LCSC on feeder cells. Gene
      expression patterns of in vitro differentiation were consistent with our in vivo
      finding; furthermore, the tumorigenicity of cloned CD34+ LCSC was not different
      from uncloned CD34+ LCSC sorted from parental PLC. These results show that our
      cloned CD34+ LCSC maintained CSC property, including self-renewal, bipotency, and
      tumorigenicity after long-term culture, demonstrating that this LCSC can be
      cultured in an unlimited manner in vitro. Thus, establishing pure population of
      CSCs isolated from the patients will provide an opportunity to explore the
      mechanisms of tumorigenesis and cancer development, and to identify unique
      biomarkers presenting potential indicators of drug efficacy against CSCs for
      establishment of a novel strategy for cancer therapy. 

PMID- 25867585
TI  - Synthesis of magnetic alginate beads based on Fe3O4 nanoparticles for the removal
      of 3-methylindole from aqueous solution using Fenton process.
AB  - A novel magnetic heterogeneous catalyst has been developed by incorporation of
      iron(II) and magnetic functionalized nanoparticles Fe3O4 in alginate beads with
      the aim of using them in the advanced Fenton oxidation of a malodorous compound
      (3 methyl-indole: 3-MI). The effects of significant operational parameters such
      as initial pH, oxidant concentration and catalyst amount were investigated and
      optimized for a better removal of 3-MI at initial concentration of 20mgL(-1).
      Besides, the catalyst stability was evaluated according to the iron leached into
      the aqueous solution. Results revealed that the parameters affecting Fenton
      catalysis must be carefully chosen to avoid excessive iron release. Under
      optimized conditions, the magnetic catalyst exhibited a good catalytic
      performance. Total removal of 3 methyl indole and a remarkable organic
      mineralization, without significant leaching of iron, were attained within 120min
      at pH 3.0 by using 0.4gL(-1) of Fe-MABs and 9.8mmolL(-1) of H2O2. The novel
      magnetic catalyst would be of potential application due to its high efficiency,
      easy recovery and good structural stability. 

PMID- 25867586
TI  - Flame temperature theory-based model for evaluation of the flammable zones of
      hydrocarbon-air-CO2 mixtures.
AB  - Theoretical models to evaluate the flammable zones of mixtures made up of
      hydrocarbon, carbon dioxide and air have been proposed in present study. A three
      step reaction hypothesis for hydrocarbon combustion was introduced for predicting
      the upper flammability limit. The method to predict the parameters at fuel
      inertization point was put forward as well. Validation of these models has been
      conducted on existing experimental data reported in the literature, including the
      cases of methane, propane, propylene and isobutane, and an acceptable precision
      has been achieved. The average relative differences between the estimated results
      and experimental ones, except for the results at fuel inertization point, are
      less than 8.8% and 3.3% for upper and lower flammability limit, respectively.
      This work also indicated that these models possess practical application capacity
      and can provide safe prediction limits for nonflammable ranges of hydrocarbon
      diluted with carbon dioxide. 

PMID- 25867587
TI  - The mechanisms for desensitization effect of synthetic polymers on BCHMX:
      Physical models and decomposition pathways.
AB  - The project involves determination of the activation energies and physical models
      for thermolysis of BCHMX and its PBXs. The initial decomposition pathways were
      also proposed on the basis of molecular dynamic simulation. The goal is to find
      the mutual relationships among the physical models, decomposition pathways, and
      the impact sensitivities for BCHMX and its PBXs. It has been shown that the
      physical model of the first step of BCHMX thermolysis is close to first order and
      the second step is governed by a first order autocatalytic model, which turns to
      "2D or 3D Nucleation and Growth" models under the effect of polymeric binders
      probably due to their hindrances on topochemical reaction of BCHMX. Simulation
      results show that the scission of N-NO2 is the initial step for BCHMX pyrolysis,
      followed by HONO and HNO eliminations, where the latter is due to nitro-nitrite
      rearrangement. Under the effect of hydrocarbon polymers, the HONO/HON elimination
      and collapse of ring structure of BCHMX occur earlier without changing the time
      for N-NO2 scission, which might be the reason why those polymers have little
      effect on the thermal stability of BCHMX, while they could make it decompose
      almost in a single complex step. 

PMID- 25867588
TI  - Two novel multi-functional magnetic adsorbents for effective removal of
      hydrophilic and hydrophobic nitroaromatic compounds.
AB  - Two novel multi-functional magnetic resins named GMA30-1 and GMA30-2 were
      fabricated and investigated for the removal of 4-nitrotoluene-2-sulfonic acid
      (NTS) and 2-nitrotoluene (o-MNT). Strong base resin (GMA30-1) and weak base resin
      (GMA30-2) possess large surface area of 718m(2)/g and 559m(2)/g, and anion
      exchange capacity of 1.49mmol/g and 1.81mmol/g, respectively. The adsorption
      isotherms of o-MNT onto two resins were both well described by Langmuir equation.
      While the adsorption isotherms of NTS could be separated into two segments at a
      certain initial concentration and each segment followed different trends. At
      lower concentrations, the adsorption of NTS was driven by Van der Waal's force,
      exhibiting an exothermic process. With the increase of concentrations, the
      electrostatic force dominated and the enthalpy change (DeltaH) turned to
      positive, indicating an endothermic process. In binary systems, the decrease in
      the uptake of NTS was slighter than that of o-MNT because of the additional anion
      exchange interaction. The adsorption capacity of NTS decreased as pH increased
      while the adsorption of o-MNT was not significantly affected by pH. Chloride ions
      reduced the adsorption of NTS by competitive effect. The desorption efficiency of
      NTS and o-MNT was close to 100% for 10 cycles. 

PMID- 25867589
TI  - Rapid degradation of Congo red by molecularly imprinted polypyrrole-coated
      magnetic TiO2 nanoparticles in dark at ambient conditions.
AB  - A novel molecularly imprinted polymer (MIP)-coated magnetic TiO2 nanocomposite
      was prepared, using methyl orange (MO) as the dummy template and pyrrole as
      functional monomer, for degradation of Congo red (CR). The nanocomposite was
      characterized by Fourier transform infrared spectroscopy, thermo-gravimetric
      analysis, X-ray diffraction, transmission electron microscopy, and vibrating
      sample magnetometer. The imprinting efficiency of the imprinted nanoparticles was
      investigated by static binding test, and their degradation ability toward CR was
      also studied. Moreover, the effects of pH, temperature, dissolved oxygen and
      oscillation rate on degradation rate of CR were investigated. Results showed that
      the imprinted nanocomposite had higher adsorption ability for MO compared with
      the non-imprinted one. Moreover, it could degrade CR rapidly in dark at room
      temperature and atmospheric pressure and could be recycled easily by a magnet
      with a good reusability. A degradation mechanism was proposed according to LC-MS
      analysis of degradation products of CR. The new imprinted nanoparticles showed
      high catalytic activity at ambient conditions without light illumination and
      additional chemicals, and therefore, it can be potentially applied to the rapid,
      "green" and low-cost degradation of CR in industrial printing and dyeing
      wastewater. 

PMID- 25867590
TI  - Nanocelluloses and their phosphorylated derivatives for selective adsorption of
      Ag(+), Cu(2+) and Fe(3+) from industrial effluents.
AB  - The potential of nanoscaled cellulose and enzymatically phosphorylated
      derivatives as bio-adsorbents to remove metal ions (Ag(+), Cu(2+) and Fe(3+))
      from model water and industrial effluents is demonstrated. Introduction of
      phosphate groups onto nanocelluloses significantly improved the metal sorption
      velocity and sorption capacity. The removal efficiency was considered to be
      driven by the high surface area of these nanomaterials as well as the nature and
      density of functional groups on the nanocellulose surface. Generally, in the
      solutions containing only single types of metal ions, the metal ion selectivity
      was in the order Ag(+)>Cu(2+)>Fe(3+), while in the case of mixtures of ions, the
      order changed to Ag(+)>Fe(3+)>Cu(2+), irrespective of the surface functionality
      of the nanocellulose. In the case of industrial effluent from the mirror making
      industry, 99% removal of Cu(2+) and Fe(3+) by phosphorylated nanocellulose was
      observed. The study showed that phosphorylated nanocelluloses are highly
      efficient biomaterials for scavenging multiple metal ions, simultaneously, from
      industrial effluents. 

PMID- 25867591
TI  - Aluminum hypophosphite microencapsulated to improve its safety and application to
      flame retardant polyamide 6.
AB  - Aluminum hypophosphite (AHP) is an effective phosphorus-containing flame
      retardant. But AHP also has fire risk that it will decompose and release
      phosphine which is spontaneously flammable in air and even can form explosive
      mixtures with air in extreme cases. In this paper, AHP has been microencapsulated
      by melamine cyanurate (MCA) to prepare microencapsulated aluminum hypophosphite
      (MCAHP) with the aim of enhancing the fire safety in the procedure of production,
      storage and use. Meanwhile, MCA was a nitrogen-containing flame retardant that
      can work with AHP via the nitrogen-phosphorus synergistic effect to show improved
      flame-retardant property than other capsule materials. After microencapsulation,
      MCA presented as a protection layer inhibit the degradation of AHP and postpone
      the generation of phosphine. Furthermore, the phosphine concentration could be
      effectively diluted by inert decomposition products of MCA. These nonflammable
      decomposition products of MCA could separate phosphine from air delay the
      oxidizing reaction with oxygen and decrease the heat release rate, which imply
      that the fire safety of AHP has been improved. Furthermore, MCAHP was added into
      polyamide 6 to prepare flame retardant polyamide 6 composites (FR-PA6) which show
      good flame retardancy. 

PMID- 25867592
TI  - Enhanced Fenton-like degradation of refractory organic compounds by surface
      complex formation of LaFeO(3) and H(2)O(2).
AB  - Nanoscale LaFeO(3) was prepared via sol-gel method and characterized by XRD, FTIR
      and N2 adsorption/desorption experiment. The results indicated that, LaFeO(3) had
      a typical perovskite structure with a BET area of 8.5m(2)/g. LaFeO(3) exhibited
      excellent Fenton activity and stability for the degradation of pharmaceuticals
      and herbicides in water, as demonstrated with sulfamethoxazole, phenazone,
      phenytoin, acyclovir and 2,4-dichlorophenoxyacetic acid, 2-chlorophenol. Among
      them, sulfamethoxazole (SMX) could be completely removed in LaFeO(3)-H(2)O(2)
      system after reaction for 120 min at neutral pH. Based on the ATR-FTIR analysis,
      the surface complex of LaFeO(3) and H(2)O(2). was formed, which was important and
      essential for the enhanced Fenton reaction by accelerating the cycle of
      Fe(3+)/Fe(2+). Hence, more OH and O(2)(-)/HO(2)(-) were then produced in LaFeO(3)
      H(2)O(2) system, resulting in more efficient removal of refractory organic
      compounds. Based on the surface interaction of LaFeO(3) and H(2)O(2), a
      heterogeneous Fenton reaction mechanism was proposed.

PMID- 25867593
TI  - Choroidal thickness in nonarteritic anterior ischemic optic neuropathy.

PMID- 25867594
TI  - Reply: To PMID 25217855.

PMID- 25867595
TI  - One-year outcomes of aflibercept in recurrent or persistent neovascular age
      related macular degeneration.

PMID- 25867596
TI  - Reply: To PMID 25461263.

PMID- 25867597
TI  - Mosaic zebrafish transgenesis for functional genomic analysis of candidate
      cooperative genes in tumor pathogenesis.
AB  - Comprehensive genomic analysis has uncovered surprisingly large numbers of
      genetic alterations in various types of cancers. To robustly and efficiently
      identify oncogenic "drivers" among these tumors and define their complex
      relationships with concurrent genetic alterations during tumor pathogenesis
      remains a daunting task. Recently, zebrafish have emerged as an important animal
      model for studying human diseases, largely because of their ease of maintenance,
      high fecundity, obvious advantages for in vivo imaging, high conservation of
      oncogenes and their molecular pathways, susceptibility to tumorigenesis and, most
      importantly, the availability of transgenic techniques suitable for use in the
      fish. Transgenic zebrafish models of cancer have been widely used to dissect
      oncogenic pathways in diverse tumor types. However, developing a stable
      transgenic fish model is both tedious and time-consuming, and it is even more
      difficult and more time-consuming to dissect the cooperation of multiple genes in
      disease pathogenesis using this approach, which requires the generation of
      multiple transgenic lines with overexpression of the individual genes of interest
      followed by complicated breeding of these stable transgenic lines. Hence, use of
      a mosaic transient transgenic approach in zebrafish offers unique advantages for
      functional genomic analysis in vivo. Briefly, candidate transgenes can be
      coinjected into one-cell-stage wild-type or transgenic zebrafish embryos and
      allowed to integrate together into each somatic cell in a mosaic pattern that
      leads to mixed genotypes in the same primarily injected animal. This permits one
      to investigate in a faster and less expensive manner whether and how the
      candidate genes can collaborate with each other to drive tumorigenesis. By
      transient overexpression of activated ALK in the transgenic fish overexpressing
      MYCN, we demonstrate here the cooperation of these two oncogenes in the
      pathogenesis of a pediatric cancer, neuroblastoma that has resisted most forms of
      contemporary treatment. 

PMID- 25867598
TI  - Neurocognitive outcomes and school performance in solid tumor cancer survivors
      lacking therapy to the central nervous system.
AB  - School performance in patients who have received therapy for childhood cancers
      has been studied in depth. Risk factors have historically included cranial
      radiation, intrathecal chemotherapy, and high doses of chemotherapy, including
      methotrexate and cytarabine. Leukemia and brain tumor survivors who receive such
      therapy have been the primary focus of this area of investigation. Extracranial
      solid tumor cancer patients lacking such risk factors have historically been
      expected to have normal school performance. We examined the medical records of 58
      young pediatric extracranial solid tumor patients who lacked CNS-directed therapy
      or other known risk factors for cognitive impairment to evaluate the incidence of
      reported difficulties or abnormalities in neuropsychological testing. Thirty-one
      percent of patients were found to have at least one reported difficulty or
      abnormality. Of note, 34% of patients with Wilms tumor possessed difficulties
      compared to 23% of patients with other extracranial solid tumors. Extracranial
      solid tumor cancer survivors without known risk factors for school performance
      difficulties appear to have a higher incidence of problems than expected. 

PMID- 25867599
TI  - Efficacy and Safety of Enzyme-Modified Panax ginseng for Anti-Wrinkle Therapy in
      Healthy Skin: A Single-Center, Randomized, Double-Blind, Placebo-Controlled
      Study.
AB  - Human skin undergoes changes during aging that result from the synergistic
      effects of intrinsic and extrinsic factors that may culminate in wrinkle
      formation, a characteristic of aged skin. Panax ginseng and ginsenosides have
      promising properties in preventing skin aging. Our previous study demonstrated
      that enzyme-modified ginseng extract (EG) has inhibitory effects against
      ultraviolet B (UVB) radiation-induced skin aging. The purpose of the current
      study was to evaluate the preventive effects of EG on eye-wrinkle formation by
      applying EG cream in 23 randomized human subjects. Compared to the placebo, EG
      significantly reduced the global photo-damage score. In addition, total roughness
      (R1), smoothness depth (R4), and arithmetic roughness average (R5) were
      significantly decreased with use of EG. In a post-study questionnaire, subjects
      responded that EG was absorbed efficiently into the skin and was more potent in
      moisturizing and softening skin than the placebo. No participants reported
      adverse reactions to treatment. In conclusion, EG sufficiently suppressed eye
      wrinkle formation by decreasing various roughness measures on the basis of
      assessment with non-invasive devices. Therefore, our results indicate that EG is
      a promising anti-aging candidate that could be used as an ingredient in natural
      functional food and cosmetic products. 

PMID- 25867601
TI  - Correction to Martinez-Corts et al. (2015).
AB  - Reports an error in "Spillover of Interpersonal Conflicts From Work into Nonwork:
      A Daily Diary Study" by Ines Martinez-Corts, Evangelia Demerouti, Arnold B.
      Bakker and Marina Boz (Journal of Occupational Health Psychology, Advanced Online
      Publication, Jan 19, 2015, np). There was a misspelling in the figures. The
      legends for Figure 1 and Figure 2 should read "High Daily Resilience". (The
      following abstract of the original article appeared in record 2015-00988-001.)
      This study among a heterogeneous sample of employees expands the Job-Demands (JD
      R) theory by examining how interpersonal conflicts at work-task and relationship
      conflict-spillover into the nonwork domain on a daily basis. We hypothesized that
      daily personal resources can buffer the daily negative spillover of interpersonal
      conflicts from work into the nonwork domain. A total of 113 employees (n = 565
      occasions) filled in a daily diary questionnaire in the evening before bedtime
      over 5 consecutive working days. Results of multilevel analysis showed that the
      presence of daily personal resources is essential to buffer the spillover of
      interpersonal conflict at work to the nonwork domain. Specifically, on days that
      employees were not very optimistic or resilient, interpersonal conflicts resulted
      in higher strain-based work-life conflict experiences. These findings contribute
      to the JD-R theory and show how the unfavorable effects of daily interpersonal
      conflicts in the work domain may be avoided in the nonwork domain through
      enhancing personal resources. We discuss the implications for theory and
      practice.

PMID- 25867600
TI  - Cultivation of Heligmosomoides polygyrus: an immunomodulatory nematode parasite
      and its secreted products.
AB  - Heligmosomoides polygyrus (formerly known as Nematospiroides dubius, and also
      referred to by some as H. bakeri) is a gastrointestinal helminth that employs
      multiple immunomodulatory mechanisms to establish chronic infection in mice and
      closely resembles prevalent human helminth infections. H. polygyrus has been
      studied extensively in the field of helminth-derived immune regulation and has
      been found to potently suppress experimental models of allergy and autoimmunity
      (both with active infection and isolated secreted products). The protocol
      described in this paper outlines management of the H. polygyrus life cycle for
      consistent production of L3 larvae, recovery of adult parasites, and collection
      of their excretory-secretory products (HES). 

PMID- 25867602
TI  - Renoprotective effect of berberine on type 2 diabetic nephropathy in rats.
AB  - Inflammation, fibrosis, and lipid disorder are essential promoters in the
      pathogenesis of diabetic kidney injury in diabetes mellitus type 2. Berberine
      (BBR) has been reported to have beneficial effects on diabetic nephropathy, but
      its action mechanism is still unclear. The present study was designed to
      elucidate the therapeutic mechanism of BBR in a type 2 diabetic nephropathy rat
      model induced by a high-fat diet and low-dose streptozotocin injection. The
      diabetic rats were treated with or without BBR by gavage for 20 weeks and
      examined by serology, 24-h albuminuria, histology, immunohistochemistry, and
      molecular analyses. Results showed that treatment with BBR significantly reduced
      serum levels of blood glucose and lipids, inhibited urinary excretion of albumin,
      and attenuated renal histological injuries in diabetic rats. Berberine treatment
      also inhibited renal inflammation, which was associated with inactivation of
      nuclear factor kappa-light-chain-enhancer of activated B-cell signalling. As a
      result, the upregulation of pro-inflammatory cytokines (interleukin-1beta, tumour
      necrosis factor-alpha) and chemokine (monocyte chemotactic protein-1) was
      blocked. In addition, BBR treatment also inactivated transforming growth factor
      beta/Smad3 signalling and suppressed renal fibrosis, including expression of
      fibronectin, collagen I, and collagen IV. The present study reveals that BBR is a
      therapeutic agent for attenuating type 2 diabetic nephropathy by inhibiting
      nuclear factor kappa-light-chain-enhancer of activated B cell-driven renal
      inflammation and transforming growth factor-beta/Smad3 signalling pathway.

PMID- 25867604
TI  - Fe-Catalyzed Direct alpha C-H Amination of Carbonyl Compounds.
AB  - A direct Fe-catalyzed alpha-amination of 1,3-dicarbonyl compounds has been
      accomplished using arylhydroxylamines as aminating agents. This novel protocol
      allows convenient access to alpha-amino carbonyl derivatives without the need for
      any postreaction manipulations. This is an operationally simple procedure that
      works at low temperatures in shorter reaction times and produces high yields with
      excellent N-selectivity. 

PMID- 25867603
TI  - The active tamoxifen metabolite endoxifen (4OHNDtam) strongly down-regulates
      cytokeratin 6 (CK6) in MCF-7 breast cancer cells.
AB  - INTRODUCTION: Tamoxifen is an anti-estrogen drug used in treatment of Estrogen
      Receptor (ER) positive breast cancer. Effects and side effects of tamoxifen is
      the sum of tamoxifen and all its metabolites. 4-Hydroxytamoxifen (4OHtam) and 4
      hydroxy-N-demethyltamoxifen (4OHNDtam, endoxifen) both have ER affinity exceeding
      that of the parent drug tamoxifen. 4OHNDtam is considered the main active
      metabolite of tamoxifen. Ndesmethyltamoxifen (NDtam) is the major tamoxifen
      metabolite. It has low affinity to the ER and is not believed to influence tumor
      growth. However, NDtam might mediate adverse effects of tamoxifen treatment. In
      this study we investigated the gene regulatory effects of the three metabolites
      of tamoxifen in MCF-7 breast cancer cells. MATERIAL AND METHODS: Using
      concentrations that mimic the clinical situation we examined effects of 4OHtam,
      4OHNDtam and NDtam on global gene expression in 17beta-estradiol (E2) treated MCF
      7 cells. Transcriptomic responses were assessed by correspondence analysis,
      differential expression, gene ontology analysis and quantitative real time PCR (Q
      rt-PCR). E2 deprivation and knockdown of Steroid Receptor Coactivator-3 (SRC
      3)/Amplified in Breast Cancer 1 (AIB1) mRNA in MCF-7 cells were performed to
      further characterize specific effects on gene expression. RESULTS: 4OHNDtam and
      4OHtam caused major changes in gene expression compared to treatment with E2
      alone, with a stronger effect of 4OHNDtam. NDtam had nearly no effect on the
      global gene expression profile. Treatment of MCF-7 cells with 4OHNDtam led to a
      strong down-regulation of the CytoKeratin 6 isoforms (KRT6A, KRT6B and KRT6C).
      The CytoKeratin 6 mRNAs were also down-regulated in MCF-7 cells after E2
      deprivation and after SRC-3/AIB1 knockdown. CONCLUSION: Using concentrations that
      mimic the clinical situation we report global gene expression changes that were
      most pronounced with 4OHNDtam and minimal with NDtam. Genes encoding CytoKeratin
      6, were highly down-regulated by 4OHNDtam, as well as after E2 deprivation and
      knockdown of SRC-3/AIB1, indicating an estrogen receptor-dependent regulation.

PMID- 25867605
TI  - Monitoring B cell subsets and alloreactivity in kidney transplantation.
AB  - B cells are the precursors of antibody producing plasma cells that can give rise
      to the formation of donor-specific antibodies. However, recent data suggest that
      besides their role in antibody production, B cells participate in antibody
      independent responses, potentially leading to allograft rejection or allograft
      tolerance. The presence of CD20(+) B cells in kidney graft biopsies has been
      shown during severe acute rejection episodes and during chronic rejection.
      Furthermore, operationally tolerant kidney transplant recipients showed a clear B
      cell dominated fingerprint of tolerance. Several techniques exist to study B
      cells on different levels. Numerous classification schemes allow for the
      distinction of many different B cell subsets using flow cytometry. Regardless,
      data on B cell subsets during stable graft function, rejection or tolerance
      remain scarce. To obtain a complete picture of the role of B cells during
      transplantation, antigen specific B cell assays may be required. Therefore,
      techniques have now been developed that allow for studying the specificity and
      frequency of HLA specific B cells. Here, we present an overview of the existent
      assays, panels and techniques intended to characterize peripheral B cells, and
      the currently available HLA specific B cell functional assays that may allow for
      monitoring the humoral alloimmune response in transplant recipients. 

PMID- 25867606
TI  - Association between serum concentrations of nitric oxide and transition to
      menopause.
AB  - OBJECTIVE: Menopausal status may increase cardiovascular disease (CVD) risk.
      Nitric oxide plays a role in the protection against CVD onset and progression but
      has not been studied around the time of menopause. We investigated associations
      between serum nitric-oxide metabolite (NOx) concentrations and menopausal status.
      DESIGN: Comparative case-control cross-sectional study. SETTING: Tehran Lipid and
      Glucose Study, university center. SAMPLE: Sub-groups from a cohort of 2137 women,
      of whom 213 met enrollment criteria. METHODS: We studied four sub-groups in a 1.2
      ratio: (1) post-menopausal women (n = 29) with natural amenorrhea for 13-24
      months, (2) age- and BMI-matched controls (n = 58) with regular menstrual cycles;
      (3) peri-menopausal women (n = 42) with natural amenorrhea for 1-12 months, and
      (4) age- and BMI-matched women as controls for the last group of women (n = 84).
      MAIN OUTCOME MEASURE: Serum nitric oxide concentrations. RESULTS: Medians (inter
      quartile ranges) of NOx in post-menopausal women and their controls were 31 (21.7
      40.2) and 23.5 (17.2-31) MUmol/L, respectively (p = 0.012). In peri-menopausal
      women and their controls the medians (inter-quartile ranges) were 28 MUmol/L
      (18.5-50.5) and 25 (20-31.25) MUmol/L, respectively (p = 0.035), but were not
      significantly different between peri- and postmenopausal women and were unchanged
      after adjustment for lipids. In a conditional fixed-effect logistic regression
      model, the risk of "transition to menopause" and "menopause" rose respectively
      2.44- and 2.27-fold for a one-score increase in the NOx standard deviation.
      CONCLUSION: Menopausal status, by itself and not as a consequence of aging, is
      associated with increased serum nitric oxide concentrations. Identification of
      variables associated with menopausal cardiovascular consequences may be used to
      improve women's health after menopause.

PMID- 25867607
TI  - Mammosphere formation assay from human breast cancer tissues and cell lines.
AB  - Similar to healthy tissues, many blood and solid malignancies are now thought to
      be organised hierarchically, with a subset of stem-like cancer cells that self
      renew while giving rise to more differentiated progeny. Understanding and
      targeting these cancer stem cells in breast cancer, which may possess enhanced
      chemo- and radio-resistance compared to the non-stem tumor bulk, has become an
      important research area. Markers including CD44, CD24, and ALDH activity can be
      assessed using fluorescence activated cell sorting (FACS) to prospectively
      isolate cells that display enhanced tumorigenicity when implanted into
      immunocompromised mice: the mammosphere assay has also become widely used for its
      ability to retrospectively identify sphere-forming cells that develop from single
      stem cell-like clones. Here we outline approaches for the appropriate culturing
      of mammospheres from cell lines or primary patient samples, their passaging, and
      calculations to estimate sphere forming efficiency (SFE). First we discuss key
      considerations and pitfalls in the appropriate planning and interpretation of
      mammosphere experiments. 

PMID- 25867608
TI  - Concomitant and hybrid therapy for Helicobacter pylori infection: A randomized
      clinical trial.
AB  - BACKGROUND AND AIMS: This study aimed to validate the equivalence of first-line
      concomitant and hybrid regimens for Helicobacter pylori infection in an era of
      increasing antibiotic resistance. The study also aimed to assess regimen
      compliance. METHODS: H. pylori-infected patients from six hospitals in Korea were
      randomly assigned to either concomitant or hybrid regimens. The concomitant
      regimen consisted of 20 mg of esomeprazole, 1 g of amoxicillin, 500 mg of
      clarithromycin, and 500 mg metronidazole, twice daily for 10 days. The hybrid
      regimen consisted of a 5-day dual therapy (20 mg of esomeprazole and 1 g of
      amoxicillin, twice daily) followed by a 5-day quadruple therapy (20 mg of
      esomeprazole, 1 g of amoxicillin, 500 mg of clarithromycin, and 500 mg of
      metronidazole, twice daily). RESULTS: Eradication rates for concomitant and
      hybrid therapy were 78.6% (187/238) and 78.8% (190/241) in the intention-to-treat
      analysis, and 89.8% (176/196) and 89.6% (181/202) in the per protocol analysis.
      For both analyses, 95% confidence intervals fell within the +/- 8% equivalence
      margin. Adherence was better in the hybrid group (95.0%) than in the concomitant
      group (90.1%), a difference that was borderline significant (P = 0.051). Adverse
      event rates were higher in the concomitant group than in the hybrid group for
      nausea (15.8% vs 8.8%; P = 0.028) and regurgitation (17.6% vs 10.7%; P = 0.040).
      CONCLUSION: As compared with concomitant therapy, hybrid therapy offered similar
      efficacy, better compliance, and fewer adverse events. Hybrid therapy could be a
      reasonable first-line treatment option for H. pylori in areas with high
      antibiotics resistance.

PMID- 25867610
TI  - Can arousal modulate response inhibition?
AB  - The goal of the present study was to examine if and how arousal can modulate
      response inhibition. Two competing hypotheses can be drawn from previous
      literature. One holds that alerting cues that elevate arousal should result in an
      impulsive response and therefore impair response inhibition. The other suggests
      that alerting enhances processing of salient events and can therefore enhance
      processing of a cue that indicates to withhold a response and improve response
      inhibition. In a stop-signal task, participants were required to withhold
      prepotent responses when a stop signal followed target onset. Abrupt alerting
      cues preceded the target in one half of the trials. The results showed that
      alerting improved response inhibition as indicated by shorter stop-signal
      reaction times following an alerting cue compared with a no-alerting condition.
      We conclude that modulation of low-level operations can influence what are
      considered to be higher cognitive functions to achieve optimal goal-directed
      behavior. However, we stress that such interactions should be treated cautiously
      as they do not always reflect direct links between lower and higher cognitive
      mechanisms.

PMID- 25867611
TI  - Misremembering what you see or hear: Dissociable effects of modality on short-
      and long-term false recognition.
AB  - False working memories readily emerge using a visual item-recognition variant of
      the converging associates task. Two experiments, manipulating study and test
      modality, extended prior working memory results by demonstrating a reliable false
      recognition effect (more false alarms to associatively related lures than to
      unrelated lures) within seconds of encoding in either the visual or auditory
      modality. However, false memories were nearly twice as frequent when study lists
      were seen than when they were heard, regardless of test modality, although study
      test modality mismatch was generally disadvantageous (consistent with encoding
      specificity). A final experiment that varied study-test modality using a hybrid
      short- and long-term memory test (Flegal, Atkins & Reuter-Lorenz, 2010)
      replicated the auditory advantage in the short term but revealed a reversal in
      the long term: The false memory effect was greater in the auditory study-test
      condition than in the visual study-test condition. Thus, the same encoding
      conditions gave rise to an opposite modality advantage depending on whether
      recognition was tested under short-term or long-term memory conditions. Although
      demonstrating continuity in associative processing across delay, the results
      indicate that delay condition affects the availability of modality-dependent
      features of the memory trace and, thus, distinctiveness, leading to dissociable
      patterns of short- and long-term memory performance.

PMID- 25867612
TI  - Correction to Mattan et al. (2014).

PMID- 25867609
TI  - The role of response bias in perceptual learning.
AB  - Sensory judgments improve with practice. Such perceptual learning is often
      thought to reflect an increase in perceptual sensitivity. However, it may also
      represent a decrease in response bias, with unpracticed observers acting in part
      on a priori hunches rather than sensory evidence. To examine whether this is the
      case, 55 observers practiced making a basic auditory judgment (yes/no amplitude
      modulation detection or forced-choice frequency/amplitude discrimination) over
      multiple days. With all tasks, bias was present initially, but decreased with
      practice. Notably, this was the case even on supposedly "bias-free," 2
      alternative forced-choice, tasks. In those tasks, observers did not favor the
      same response throughout (stationary bias), but did favor whichever response had
      been correct on previous trials (nonstationary bias). Means of correcting for
      bias are described. When applied, these showed that at least 13% of perceptual
      learning on a forced-choice task was due to reduction in bias. In other
      situations, changes in bias were shown to obscure the true extent of learning,
      with changes in estimated sensitivity increasing once bias was corrected for. The
      possible causes of bias and the implications for our understanding of perceptual
      learning are discussed.

PMID- 25867613
TI  - Forgotten but not gone: Retro-cue costs and benefits in a double-cueing paradigm
      suggest multiple states in visual short-term memory.
AB  - Visual short-term memory (VSTM) performance is enhanced when the to-be-tested
      item is cued after encoding. This so-called retro-cue benefit is typically
      accompanied by a cost for the noncued items, suggesting that information is lost
      from VSTM upon presentation of a retrospective cue. Here we assessed whether
      noncued items can be restored to VSTM when made relevant again by a subsequent
      second cue. We presented either 1 or 2 consecutive retro-cues (80% valid) during
      the retention interval of a change-detection task. Relative to no cue, a valid
      cue increased VSTM capacity by 2 items, while an invalid cue decreased capacity
      by 2. Importantly, when a second, valid cue followed an invalid cue, capacity
      regained 2 items, so that performance was back on par. In addition, when the
      second cue was also invalid, there was no extra loss of information from VSTM,
      suggesting that those items that survived a first invalid cue, automatically also
      survived a second. We conclude that these results are in support of a very
      versatile VSTM system, in which memoranda adopt different representational states
      depending on whether they are deemed relevant now, in the future, or not at all.
      We discuss a neural model that is consistent with this conclusion.

PMID- 25867614
TI  - Remembering to prepare: The benefits (and costs) of high working memory capacity.
AB  - The dual mechanisms of control framework postulates that cognitive control can
      operate in 2 distinct modes: a "proactive" preparatory mode and a "reactive" wait
      and-see mode. Importantly, the 2 modes are associated with both costs and
      benefits in cognitive performance. Here we explore this framework, in terms of
      its relationship with working memory capacity (WMC). We hypothesize that high-WMC
      individuals are more likely to utilize proactive control yielding not only
      benefits, but also specific costs to performance. Across 2 separate, large-sample
      experiments, healthy young adults performed different variants of the AX
      Continuous Performance Test context processing task, a well-established probe of
      proactive and reactive cognitive control. In 2 experiments, WMC predicted both
      improvements and relative impairments in task performance in a manner that was
      consistent with usage of proactive control. These findings suggest that
      individuals differ in the degree to which they utilize proactive control based on
      WMC.

PMID- 25867615
TI  - Central and peripheral vision loss differentially affects contextual cueing in
      visual search.
AB  - Visual search for targets in repeated displays is more efficient than search for
      the same targets in random distractor layouts. Previous work has shown that this
      contextual cueing is severely impaired under central vision loss. Here, we
      investigated whether central vision loss, simulated with gaze-contingent
      displays, prevents the incidental learning of contextual cues or the expression
      of learning, that is, the guidance of search by learned target-distractor
      configurations. Visual search with a central scotoma reduced contextual cueing
      both with respect to search times and gaze parameters. However, when the scotoma
      was subsequently removed, contextual cueing was observed in a comparable
      magnitude as for controls who had searched without scotoma simulation throughout
      the experiment. This indicated that search with a central scotoma did not prevent
      incidental context learning, but interfered with search guidance by learned
      contexts. We discuss the role of visuospatial working memory load as source of
      this interference. In contrast to central vision loss, peripheral vision loss was
      expected to prevent spatial configuration learning itself, because the restricted
      search window did not allow the integration of invariant local configurations
      with the global display layout. This expectation was confirmed in that visual
      search with a simulated peripheral scotoma eliminated contextual cueing not only
      in the initial learning phase with scotoma, but also in the subsequent test phase
      without scotoma.

PMID- 25867616
TI  - The extended transorbital craniotomy: an anatomic study.
AB  - BACKGROUND: Supra-/transorbital approaches are mostly limited to suprasellar and
      anterior fossa pathologies, whereas lateral supraorbital approaches provide less
      retrosellar exposure and less overall operative volume, especially in the
      temporal region. OBJECTIVE: Our cadaveric study proposes removal of the lesser
      and greater wings of the sphenoid bone to increase both the lateral angle
      typically achieved with pterional approaches and exposure to the temporal lobe
      and perisellar region. METHODS: In 5 cadaveric specimens, our 3 steps to expand
      transorbital exposures included the following: step 1, standard transorbital
      craniotomy via a 3-cm supra-eyebrow incision; step 2, removal of the lesser
      sphenoid wing completed extradurally; and step 3, partial removal of the greater
      sphenoid wing. Operative extension in sylvian, parasellar, and anterolateral
      temporal exposures were quantified for each step (t test). RESULTS: Step 2
      provided the greatest increased exposure in the sylvian and parasellar regions
      compared with step 3, whereas step 3 provided a significant proportion of the
      exposure in the lateral temporal region. Finally, the lateral view progressively
      increased with each subsequent step. CONCLUSION: Our 3-step removal of the lesser
      and greater wings of the sphenoid bone quantified increased sylvian, anterior
      temporal, and parasellar exposures for this minimally invasive approach with
      excellent cosmesis. Its increases the anterolateral view (similar to a subfrontal
      pterional approach) and offers potential applications to vascular and neoplastic
      (ie, sphenoid meningiomas) pathologies classically treated via a pterional or
      frontotemporal orbitozygomatic approach.

PMID- 25867617
TI  - Blood typing using microstructured waveguide smart cuvette.
AB  - We introduce a sensitive method that allows one to distinguish positive and
      negative agglutination reactions used for blood typing and determination of Rh
      affinity with a high precision. The method is based on the unique properties of
      photonic crystal waveguides, i.e., microstructured waveguides (MSWs). The
      transmission spectrum of an MSW smart cuvette filled by a specific or nonspecific
      agglutinating serum depends on the scattering, refractive, and absorptive
      properties of the blood probe. This concept was proven in the course of a
      laboratory clinical study. The obtained ratio of the spectral-based
      discrimination parameter for positive and negative reactions (I+/I-) was found to
      be 16 for standard analysis and around 2 for used sera with a weak activity.

PMID- 25867618
TI  - Research on the change of complex refractive index of porcine muscle during
      natural dehydration.
AB  - The physical changes of tissue are complicated to evaluate during optical
      clearing (OC) treatment. Monitoring the changes of optical parameters, including
      the complex refractive index (CRI), helps people better understand the OC
      process. From the imaginary part of CRI, we can deduce the extinction coefficient
      of tissue. Based on the total internal reflection method, the time-dependent CRI
      of porcine muscle during natural dehydration is well determined. Results show
      that the real RI increases continuously with the increase of dehydration time,
      whereas the extinction coefficient initially increases and then decreases.
      Finally, the extinction coefficient becomes much smaller than the initial value,
      which demonstrates that better tissue optical clarity is obtained. The change
      tendency of the extinction coefficient of tissue is used to qualitatively explain
      the dynamic change of transmittance of a natural dehydrated tissue. Consequently,
      CRI, especially its imaginary part, is a very useful optical parameter by which
      to evaluate the OC effect.

PMID- 25867619
TI  - Hyperspectral imaging-based wound analysis using mixture-tuned matched filtering
      classification method.
AB  - Hyperspectral imaging is a technology that is beginning to occupy an important
      place in medical research with good prospects in future clinical applications. We
      evaluated the role of hyperspectral imaging in association with a mixture-tuned
      matched filtering method in the characterization of open wounds. The methodology
      and the processing steps of the hyperspectral image that have been performed in
      order to obtain the most useful information about the wound are described in
      detail. Correlations between the hyperspectral image and clinical examination are
      described, leading to a pattern that permits relative evaluation of the square
      area of the wound and its different components in comparison with the surrounding
      normal skin. Our results showed that the described method can identify different
      types of tissues that are present in the wounded area and can objectively measure
      their respective abundance, which proves its value in wound characterization. In
      conclusion, the method that was described in this preliminary case presentation
      shows promising results, but needs further evaluation in order to become a
      reliable and useful tool.

PMID- 25867620
TI  - Multimodal optical measurement in vitro of surface deformations and wall
      thickness of the pressurized aortic arch.
AB  - Computational modeling of arterial mechanics continues to progress, even to the
      point of allowing the study of complex regions such as the aortic arch.
      Nevertheless, most prior studies assign homogeneous and isotropic material
      properties and constant wall thickness even when implementing patient-specific
      luminal geometries obtained from medical imaging. These assumptions are not due
      to computational limitations, but rather to the lack of spatially dense sets of
      experimental data that describe regional variations in mechanical properties and
      wall thickness in such complex arterial regions. In this work, we addressed
      technical challenges associated with in vitro measurement of overall geometry,
      full-field surface deformations, and regional wall thickness of the porcine
      aortic arch in its native anatomical configuration. Specifically, we combined two
      digital image correlation-based approaches, standard and panoramic, to track
      surface geometry and finite deformations during pressurization, with a 360-deg
      fringe projection system to contour the outer and inner geometry. The latter
      provided, for the first time, information on heterogeneous distributions of wall
      thickness of the arch and associated branches in the unloaded state. Results
      showed that mechanical responses vary significantly with orientation and location
      (e.g., less extensible in the circumferential direction and with increasing
      distance from the heart) and that the arch exhibits a nearly linear increase in
      pressure-induced strain up to 40%, consistent with other findings on proximal
      porcine aortas. Thickness measurements revealed strong regional differences, thus
      emphasizing the need to include nonuniform thicknesses in theoretical and
      computational studies of complex arterial geometries.

PMID- 25867621
TI  - Broad Clinical Phenotype and Facets of Emotion Regulation in Interpersonal Trauma
      Survivors.
AB  - OBJECTIVES: This study examines broad-based psychopathology in a community sample
      of female survivors of interpersonal trauma. The extent to which facets of
      emotion regulation predict symptom presentation among this population is
      examined. METHOD: Hierarchical cluster analysis examining symptoms of
      posttraumatic stress disorder, depression, somatization, and alcohol abuse was
      used to identify symptom clusters in an ethnically diverse sample (N = 205).
      RESULTS: Approximately 17% of the sample fell into a severe symptom group
      characterized by clinical levels of distress across all four disorders. The
      largest group (46%) was marked by subclinical distress across all four disorders,
      while the final group (37%) reported subclinical distress, but with a relative
      absence of alcohol abuse. Of the 6 emotion regulation subscales from the
      Difficulties in Emotion Regulation Scale (Gratz & Roemer, 2004), 2 consistently
      predicted group membership: nonacceptance and impulsivity. CONCLUSIONS: Cluster
      analyses revealed symptom clusters that may vary in their appropriateness for
      current posttrauma interventions. Implications for research and clinical practice
      are discussed.

PMID- 25867622
TI  - Epidemiology of extensive drug resistant Acinetobacter baumannii (XDRAB) at
      Security Forces Hospital (SFH) in Kingdom of Saudi Arabia (KSA).
AB  - OBJECTIVES: Extensively drug-resistant Acinetobacter baumannii (XDRAB) became a
      worldwide nosocomial threat. The aim of this study was to assess the epidemiology
      and to evaluate the prevalence of carbapenem-resistant A. baumannii (CRAB). We
      also discuss therapeutic options for the management of their infections. METHODS:
      Antibiotic susceptibility was determined in 506, 510 and 936 duplicate isolates
      of A. baumannii isolated in 2006, 2009 and 2012, respectively. In 2012, 12 unique
      XDRAB strains were isolated from patients with serious ventilator-associated
      pneumonia (VAP). Susceptibility tests were performed using the microdilution
      method according to Clinical and Laboratory Standards Institute (CLSI)
      recommendations. MICs were determined in triplicate by E-test according to the
      manufacturer's recommendations. Susceptible and multidrug-resistant A. baumannii
      (MDRAB) strains were detected using CHROMagar Acinetobacter medium. Carbapenem
      resistant A. baumannii was investigated for carbapenemase production by the
      modified Hodge test (MHT) and by multiplex PCR. A Synergy test was performed
      using the E-test method. RESULTS: Considering years 2006, 2009 and 2012, the
      susceptibilities to meropenem and imipenem were 64-81.2%, 34.5-45.3%, and 8.3
      11%, respectively. Concerning the 12 XDRAB strains, all isolates were susceptible
      to colistin and resistant to meropenem and imipenem. Culture on CHROMagar
      Acinetobacter confirmed that all are MDRAB. The gene profiles detected in PCR
      assays showed that all the strains possess OXA-51.Out of the 12 isolates, 11
      possess the oxa-23 gene and one harbours the gene 24/40. A good synergistic
      effect was detected between colistin and tigecycline. CONCLUSIONS: In this study,
      A. baumannii susceptibility to carbapenems showed a drastic reduction and
      represents a major epidemiological concern. The main carbapenem resistance
      mechanism is mediated by class D-OXA-type enzymes (oxa-23 and oxa-24/40) with
      Carbapenemase activity. Therapeutic options are exceedingly limited, relying on
      polymyxin combinations with other antibiotics. We are clearly missing new active
      agents against XDRAB.

PMID- 25867623
TI  - Genome-wide identification, classification, and expression analysis of 14-3-3
      gene family in Populus.
AB  - BACKGROUND: In plants, 14-3-3 proteins are encoded by a large multigene family
      and are involved in signaling pathways to regulate plant development and
      protection from stress. Although twelve Populus 14-3-3s were identified based on
      the Populus trichocarpa genome V1.1 in a previous study, no systematic analysis
      including genome organization, gene structure, duplication relationship,
      evolutionary analysis and expression compendium has been conducted in Populus
      based on the latest P. trichocarpa genome V3.0. PRINCIPAL FINDINGS: Here, a
      comprehensive analysis of Populus 14-3-3 family is presented. Two new 14-3-3
      genes were identified based on the latest P. trichocarpa genome. In P.
      trichocarpa, fourteen 14-3-3 genes were grouped into epsilon and non-epsilon
      group. Exon-intron organizations of Populus 14-3-3s are highly conserved within
      the same group. Genomic organization analysis indicated that purifying selection
      plays a pivotal role in the retention and maintenance of Populus 14-3-3 family.
      Protein conformational analysis indicated that Populus 14-3-3 consists of a
      bundle of nine alpha-helices (alpha1-alpha9); the first four are essential for
      formation of the dimer, while alpha3, alpha5, alpha7, and alpha9 form a conserved
      peptide-binding groove. In addition, alpha1, alpha3, alpha5, alpha7, and alpha9
      were evolving at a lower rate, while alpha2, alpha4, and alpha6 were evolving at
      a relatively faster rate. Microarray analyses showed that most Populus 14-3-3s
      are differentially expressed across tissues and upon exposure to various
      stresses. CONCLUSIONS: The gene structures and their coding protein structures of
      Populus 14-3-3s are highly conserved among group members, suggesting that members
      of the same group might also have conserved functions. Microarray and qRT-PCR
      analyses showed that most Populus 14-3-3s were differentially expressed in
      various tissues and were induced by various stresses. Our investigation provided
      a better understanding of the complexity of the 14-3-3 gene family in poplars.

PMID- 25867624
TI  - Facilitators of adherence to the study pill in the FEM-PrEP clinical trial.
AB  - INTRODUCTION: FEM-PrEP did not demonstrate a reduction in HIV acquisition because
      of low study pill adherence. Yet, plasma and intracellular drug concentrations
      indicated that some participants had evidence of recent pill use. We conducted a
      follow-up study to identify, among other topics, participants' reasons for taking
      the study pill. METHODS: Qualitative, semi-structured interviews (SSIs) were
      conducted with 88 FEM-PrEP participants. Participants were purposefully selected
      based on their adherence drug concentrations collected during FEM-PrEP and placed
      into three adherence interview groups: "high," "moderate," and "none/scarce."
      Participants in the high and moderate groups described reasons why they adhered
      most or some of the time, including factors that facilitated their adherence.
      Participants in all groups described what they believed made it possible for
      other FEM-PrEP participants to adhere. In addition, 224 FEM-PrEP participants
      reported on their reasons for taking the study pills through a quantitative,
      audio computer-assisted self-interview (ACASI). Thematic analysis and descriptive
      statistics were used to analyze the qualitative and quantitative data,
      respectively. RESULTS: Five themes were identified from the SSIs as facilitating
      factors of adherence: 1) participants' support for the research, 2) HIV risk
      reduction, 3) routine formation and use of tools, 4) adherence counseling, and 5)
      partner awareness and support. Participants described similar facilitators when
      they spoke about other participants' adherence. Among the 172 participants who
      reported in ACASI that they had taken a study pill, wanting to help answer the
      research question was the most frequently stated reason for taking the pills
      (94%, n = 161). We also found evidence of preventive misconception. CONCLUSIONS:
      Adherence was facilitated by personal motivations, such as risk reduction and
      interest in the research outcome, and by adherence strategies consisting of
      external cues, reminders, and support. These findings can inform future HIV
      prevention clinical trials and the rollout of effective antiretroviral-based HIV
      prevention technologies for women.

PMID- 25867625
TI  - Priming of seeds with methyl jasmonate induced resistance to hemi-biotroph
      Fusarium oxysporum f.sp. lycopersici in tomato via 12-oxo-phytodienoic acid,
      salicylic acid, and flavonol accumulation.
AB  - Methyl jasmonate (MeJA) was tested by seed treatment for its ability to protect
      tomato seedlings against fusarium wilt caused by the soil-borne fungal pathogen
      Fusarium oxysporum f.sp. lycopersici. Isolated from Solanum lycopersicon L.
      seeds, cv. Beta fungus was identified as F. oxysporum f.sp. lycopersici Race 3
      fungus by using phytopathological and molecular methods. MeJA applied at 0.01,
      0.1 and 1 mM reduced spore germination and mycelial growth in vitro. Soaking of
      tomato seeds in MeJA solution at 0.1 mM for 1 h significantly enhanced the
      resistance level against the tested fungus in tomato seedlings 4 weeks after
      inoculation. The extracts from leaves of 15-day-old seedlings obtained from
      previously MeJA soaked seeds had the ability to inhibit in vitro spore
      germination of tested fungus. In these seedlings a significant increase in the
      levels phenolic compounds such as salicylic acid (SA), kaempferol and quercetin
      was observed. Up-regulation of phenylalanine ammonia-lyase (PAL5) and benzoic
      acid/salicylic acid carboxyl methyltransferase (BSMT) genes and down-regulation
      of the isochorysmate synthase (ICS) gene in response to exogenous MeJA
      application indicate that the phenylalanine ammonia-lyase (PAL), not the
      isochorismate (IC) pathway, is the primary route for SA production in tomato.
      Moreover, the increased accumulation of the flavonols quercetin and kaempferol
      appears closely related to the increase of PAL5, chalcone synthase (CHS) and
      flavonol synthase/flavanone 3-hydroxylase-like (FLS) genes. Elevated levels of
      salicylic acid in seedlings raised from MeJA-soaked seeds were simultaneously
      accompanied by a decrease of jasmonic acid, the precursor of MeJA, and an
      increase of 12-oxo-phytodienoic acid (OPDA), the precursor of jasmonic acid. The
      present results indicate that the priming of tomato seeds with 0.1mM MeJA before
      sowing enables the seedlings grown from these seeds to reduce the attack of the
      soil-borne fungal pathogen F. oxysporum f.sp. lycopersici, so it can be applied
      in practice.

PMID- 25867626
TI  - Ligand-induced evolution of intrinsic fluorescence and catalytic activity from
      cobalt ferrite nanoparticles.
AB  - To develop CoFe(2)O(4) as magneto-fluorescent nanoparticles (NPs) for biomedical
      applications, it would be advantageous to identify any intrinsic fluorescence of
      this important magnetic material by simply adjusting the surface chemistry of the
      NPs themselves. Herein, we demonstrate that intrinsic multicolor fluorescence,
      covering the whole visible region, can be induced by facile functionalization of
      CoFe(2)O(4) NPs with Na-tartrate. Moreover, the functionalized CoFe(2)O(4) NPs
      also show unprecedented catalytic efficiency in the degradation of both
      biologically and environmentally harmful dyes, pioneering the potential
      application of these NPs in therapeutics and wastewater treatment. Detailed
      investigation through various spectroscopic tools unveils the story behind the
      emergence of this unique optical property of CoFe(2)O(4) NPs upon
      functionalization with tartrate ligands. We believe our developed multifunctional
      CoFe(2)O(4) NPs hold great promise for advanced biomedical and technological
      applications.

PMID- 25867627
TI  - Laser-induced forward transfer for flip-chip packaging of single dies.
AB  - Flip-chip (FC) packaging is a key technology for realizing high performance,
      ultra-miniaturized and high-density circuits in the micro-electronics industry.
      In this technique the chip and/or the substrate is bumped and the two are bonded
      via these conductive bumps. Many bumping techniques have been developed and
      intensively investigated since the introduction of the FC technology in 1960(1)
      such as stencil printing, stud bumping, evaporation and
      electroless/electroplating2. Despite the progress that these methods have made
      they all suffer from one or more than one drawbacks that need to be addressed
      such as cost, complex processing steps, high processing temperatures,
      manufacturing time and most importantly the lack of flexibility. In this paper,
      we demonstrate a simple and cost-effective laser-based bump forming technique
      known as Laser-induced Forward Transfer (LIFT)3. Using the LIFT technique a wide
      range of bump materials can be printed in a single-step with great flexibility,
      high speed and accuracy at RT. In addition, LIFT enables the bumping and bonding
      down to chip-scale, which is critical for fabricating ultra-miniature circuitry.

PMID- 25867629
TI  - Three abdominal defects, three pedicled flaps.
AB  - The reconstruction of complex defects in the abdominal wall after wound infection
      or trauma can be challenging. In this article, a superficial inferior epigastric
      artery flap, a tensor fascia lata flap, and an anterolateral thigh flap used for
      3 different abdominal wall reconstructions are described. The authors conclude
      that different specific abdominal wall defects can be successfully reconstructed
      using different pedicled flaps in simple and effective single-stage
      reconstructions. 

PMID- 25867628
TI  - Ensuring transmission through dynamic host environments: host-pathogen
      interactions in Plasmodium sexual development.
AB  - A renewed global commitment to malaria elimination lends urgency to understanding
      the biology of Plasmodium transmission stages. Recent progress toward uncovering
      the mechanisms underlying Plasmodium falciparum sexual differentiation and
      maturation reveals potential targets for transmission-blocking drugs and
      vaccines. The identification of parasite factors that alter sexual
      differentiation, including extracellular vesicles and a master transcriptional
      regulator, suggest that parasites make epigenetically controlled developmental
      decisions based on environmental cues. New insights into sexual development,
      especially host cell remodeling and sequestration in the bone marrow, highlight
      open questions regarding parasite homing to the tissue, transmigration across the
      vascular endothelium, and maturation in the parenchyma. Novel molecular and
      translational tools will provide further opportunities to define host-parasite
      interactions and design effective transmission-blocking therapeutics. 

PMID- 25867630
TI  - Bioengineered human dermal tissue grafting of necrobiosis lipoidica diabeticorum
      ulcerations: a case series.
AB  - A retrospective case series of sequential patients with recurrent ulcerations
      associated with necrobiosis lipoidica diabeticorum (NLD) is presented. Standard
      wound care required 40 +/- 7.21 weeks to attain complete epithelialization.
      Standard wound care plus weekly applications of bioengineered neonatal human
      dermal tissue shortened healing to 7.14 +/- 3.44 weeks.    . 

PMID- 25867631
TI  - Perspectives in prevention and treatment of surgical site infection - a narrative
      review of the literature.
AB  - Health care-associated infections (HCAIs) are infections acquired through contact
      with any aspect of health care. They can cause minor complications or serious
      disability or death, and can involve a wide variety of resistant or emergent
      organisms. Surgical site infections make up approximately one-fifth of HCAIs, and
      at least 5% of patients undergoing open surgery develop an SSI. Surgical site
      infections are probably the most preventable HCAI but have received the least
      attention; although that is changing with increased surveillance and public
      awareness of published data of individual specialty and hospital incidence rates.
      Surgical site infection continues to be a complication of surgical care. These
      infections span a continuum of severity with some being quite innocent and easy
      to manage, while others are life-threatening. Considerable evidence provides
      direction in the prevention of SSI (eg, systemic antibiotic prophylaxis) but many
      preventive strategies need better definition, with additional clinical studies.
      When SSI occurs, the clinician needs to quickly recognize it and tailor
      management to the specific needs of the patient. In general, drainage,
      debridement, and specific antibiotics for the putative pathogen are the hallmarks
      of management.  . 

PMID- 25867632
TI  - Negative pressure dressing in split-thickness skin grafts: experience with an
      alternative method.
AB  - BACKGROUND: The use of negative pressure in the dressing of splitthickness skin
      grafts has been shown to promote healing by a variety of mechanisms, including a
      decrease in interstitial edema, an increase in perfusion, and a decrease in
      bacterial colonization. METHODS: An observational study was performed on 52
      patients at the Department of Plastic Surgery, University of Perugia in Perugia,
      Italy, undergoing split-thickness skin grafting for acute wounds after trauma and
      for chronic wounds, such as pressure ulcers and diabetic wounds. The dressing
      used consisted of a single foam sheet, a conventional disposable closed-system
      suction drain, and an adhesive dressing. RESULTS: In all patients, there was a
      95% take of the graft, with 5% of partial loss. There were no significant
      complications encountered. CONCLUSIONS: Negative pressure wound therapy is an
      innovative and commercially successful concept for the management of difficultto-
      treat wounds of nearly every etiology, and the authors' technique is an
      alternative to commercially available negative pressure dressings.   .

PMID- 25867634
TI  - A small volume bioassay to assess bacterial/phytoplankton co-culture using WATER
      Pulse-Amplitude-Modulated (WATER-PAM) fluorometry.
AB  - Conventional methods for experimental manipulation of microalgae have employed
      large volumes of culture (20 ml to 5 L), so that the culture can be subsampled
      throughout the experiment1-7. Subsampling of large volumes can be problematic for
      several reasons: 1) it causes variation in the total volume and the surface
      area:volume ratio of the culture during the experiment; 2) pseudo-replication
      (i.e., replicate samples from the same treatment flask8) is often employed rather
      than true replicates (i.e., sampling from replicate treatments); 3) the duration
      of the experiment is limited by the total volume; and 4) axenic cultures or the
      usual bacterial microbiota are difficult to maintain during long-term experiments
      as contamination commonly occurs during subsampling. The use of microtiter plates
      enables 1 ml culture volumes to be used for each replicate, with up to 48
      separate treatments within a 12.65x8.5x2.2 cm plate, thereby decreasing the
      experimental volume and allowing for extensive replication without subsampling
      any treatment. Additionally, this technique can be modified to fit a variety of
      experimental formats including: bacterial-algal co-cultures, algal physiology
      tests, and toxin screening9-11. Individual wells with an alga, bacterium and/or
      co-cultures can be sampled for numerous laboratory procedures including, but not
      limited to: WATER-Pulse-Amplitude-Modulated (WATER-PAM) fluorometry, microscopy,
      bacterial colony forming unit (cfu) counts and flow cytometry. The combination of
      the microtiter plate format and WATER-PAM fluorometry allows for multiple rapid
      measurements of photochemical yield and other photochemical parameters with low
      variability between samples, high reproducibility and avoids the many pitfalls of
      subsampling a carboy or conical flask over the course of an experiment.

PMID- 25867633
TI  - Iron-hepcidin dysmetabolism, anemia and renal hypoxia, inflammation and fibrosis
      in the remnant kidney rat model.
AB  - Anemia is a common complication of chronic kidney disease (CKD) that develops
      early and its severity increases as renal function declines. It is mainly due to
      a reduced production of erythropoietin (EPO) by the kidneys; however, there are
      evidences that iron metabolism disturbances increase as CKD progresses. Our aim
      was to study the mechanisms underlying the development of anemia of CKD, as well
      as renal damage, in the remnant kidney rat model of CKD induced by 5/6
      nephrectomy. This model of CKD presented a sustained degree of renal dysfunction,
      with mild and advanced glomerular and tubulointerstitial lesions. Anemia
      developed 3 weeks after nephrectomy and persisted throughout the protocol. The
      remnant kidney was still able to produce EPO and the liver showed an increased
      EPO gene expression. In spite of the increased EPO blood levels, anemia persisted
      and was linked to low serum iron and transferrin levels, while serum interleukin
      (IL)-6 and high sensitivity C-reactive protein (hs-CRP) levels showed the absence
      of systemic inflammation. The increased expression of duodenal ferroportin
      favours iron absorption; however, serum iron is reduced which might be due to
      iron leakage through advanced kidney lesions, as showed by tubular iron
      accumulation. Our data suggest that the persistence of anemia may result from
      disturbances in iron metabolism and by an altered activity/function of EPO as a
      result of kidney cell damage and a local inflammatory milieu, as showed by the
      increased gene expression of different inflammatory proteins in the remnant
      kidney. In addition, this anemia and the associated kidney hypoxia favour the
      development of fibrosis, angiogenesis and inflammation that may underlie a
      resistance to EPO stimuli and reduced iron availability. These findings might
      contribute to open new windows to identify putative therapeutic targets for this
      condition, as well as for recombinant human EPO (rHuEPO) resistance, which occurs
      in a considerable percentage of CKD patients. 

PMID- 25867635
TI  - Chitosan/interfering RNA nanoparticle mediated gene silencing in disease vector
      mosquito larvae.
AB  - Vector mosquitoes inflict more human suffering than any other organism-and kill
      more than one million people each year. The mosquito genome projects facilitated
      research in new facets of mosquito biology, including functional genetic studies
      in the primary African malaria vector Anopheles gambiae and the dengue and yellow
      fever vector Aedes aegypti. RNA interference- (RNAi-) mediated gene silencing has
      been used to target genes of interest in both of these disease vector mosquito
      species. Here, we describe a procedure for preparation of chitosan/interfering
      RNA nanoparticles that are combined with food and ingested by larvae. This
      technically straightforward, high-throughput, and relatively inexpensive
      methodology, which is compatible with long double stranded RNA (dsRNA) or small
      interfering RNA (siRNA) molecules, has been used for the successful knockdown of
      a number of different genes in A. gambiae and A. aegypti larvae. Following larval
      feedings, knockdown, which is verified through qRT-PCR or in situ hybridization,
      can persist at least through the late pupal stage. This methodology may be
      applicable to a wide variety of mosquito and other insect species, including
      agricultural pests, as well as other non-model organisms. In addition to its
      utility in the research laboratory, in the future, chitosan, an inexpensive, non
      toxic and biodegradable polymer, could potentially be utilized in the field. 

PMID- 25867636
TI  - Surface roughened zirconia: towards hydrothermal stability.
AB  - Surface roughness is needed in several yttria-stabilized zirconia components used
      in restorative dentistry for osseointegration or adhesion purposes. This can be
      achieved by different treatments, which may also modify the microstructure of the
      surface. Among them, sandblasting and chemical etching are widely used, but their
      effect on hydrothermal aging of zirconia is not fully understood. In the present
      work, the zirconia long-term stability of rough surfaces prepared by these
      techniques is analyzed and a method is proposed for preventing hydrothermal aging
      while maintaining the original surface appearance and mechanical properties. The
      method involves pressure infiltration of a Cerium salt solution on the roughened
      surfaces followed by a thermal treatment. The solution, trapped by surface
      defects and small pores, is decomposed during thermal treatment into Cerium
      oxide, which is diffused at high temperature, obtaining Ce co-doping in the near
      surface region. In addition, the microstructural changes induced in the near
      surface by sandblasting or chemical etching are removed by the thermal treatment
      together with surface defects. No color modification was observed and the final
      roughness parameters were in the range of existing implants of proved good
      osseointegration. The aging resistance of Ce co-doped materials was strongly
      enhanced, showing the absence of aging after artificial degradation, increasing
      in this way the surface mechanical integrity. The proposed treatment is easily
      applicable to the current manufacturing procedures of zirconia dental posts,
      abutments, crowns and dentures, representing a solution to hydrothermal aging in
      these and other biomedical applications. 

PMID- 25867637
TI  - Highly Enhanced Sensing Properties for ZnO Nanoparticle-Decorated Round-Edged
      alpha-Fe2O3 Hexahedrons.
AB  - ZnO/alpha-Fe2O3 composites built from plenty of ZnO nanoparticles decorated on
      the surfaces of uniform round-edged alpha-Fe2O3 hexahedrons were successfully
      prepared via a facile solvothermal method. Various techniques were employed to
      obtain the crystalline and morphological characterization of the as-prepared
      samples. In addition, a comparative sensing performance investigation between the
      two kinds of sensing materials clearly demonstrated that the sensing properties
      of ZnO/alpha-Fe2O3 composites were substantially enhanced compared with those of
      the single alpha-Fe2O3 component, which manifest the superiority of the ZnO
      decoration as we expected. For instance, the response of ZnO/alpha-Fe2O3
      composites to 100 ppm acetone is ~30, which is ~3.15-fold higher than that of
      primary alpha-Fe2O3 hexahedrons. The synergetic effect is believed to be the
      source of the improvement of gas-sensing properties. 

PMID- 25867638
TI  - Defect-Tolerant Aligned Dipoles within Two-Dimensional Plastic Lattices.
AB  - Carboranethiol molecules self-assemble into upright molecular monolayers on
      Au{111} with aligned dipoles in two dimensions. The positions and offsets of each
      molecule's geometric apex and local dipole moment are measured and correlated
      with sub-Angstrom precision. Juxtaposing simultaneously acquired images, we
      observe monodirectional offsets between the molecular apexes and dipole extrema.
      We determine dipole orientations using efficient new image analysis techniques
      and find aligned dipoles to be highly defect tolerant, crossing molecular domain
      boundaries and substrate step edges. The alignment observed, consistent with
      Monte Carlo simulations, forms through favorable intermolecular dipole-dipole
      interactions. 

PMID- 25867639
TI  - Molecular and morphological analyses reveal phylogenetic relationships of
      stingrays focusing on the family Dasyatidae (Myliobatiformes).
AB  - Elucidating the phylogenetic relationships of the current but problematic
      Dasyatidae (Order Myliobatiformes) was the first priority of the current study.
      Here, we studied three molecular gene markers of 43 species (COI gene), 33
      species (ND2 gene) and 34 species (RAG1 gene) of stingrays to draft out the
      phylogenetic tree of the order. Nine character states were identified and used to
      confirm the molecularly constructed phylogenetic trees. Eight or more clades (at
      different hierarchical level) were identified for COI, ND2 and RAG1 genes in the
      Myliobatiformes including four clades containing members of the present
      Dasyatidae, thus rendering the latter non-monophyletic. The uncorrected p
      distance between these four 'Dasytidae' clades when compared to the distance
      between formally known families confirmed that these four clades should be
      elevated to four separate families. We suggest a revision of the present
      classification, retaining the Dasyatidae (Dasyatis and Taeniurops species) but
      adding three new families namely, Neotrygonidae (Neotrygon and Taeniura species),
      Himanturidae (Himantura species) and Pastinachidae (Pastinachus species). Our
      result indicated the need to further review the classification of Dasyatis
      microps. By resolving the non-monophyletic problem, the suite of nine character
      states enables the natural classification of the Myliobatiformes into at least
      thirteen families based on morphology. 

PMID- 25867640
TI  - Non-equilibrium scale invariance and shortcuts to adiabaticity in a one
      dimensional Bose gas.
AB  - We present experimental evidence for scale invariant behaviour of the excitation
      spectrum in phase-fluctuating quasi-1d Bose gases after a rapid change of the
      external trapping potential. Probing density correlations in free expansion, we
      find that the temperature of an initial thermal state scales with the spatial
      extension of the cloud as predicted by a model based on adiabatic rescaling of
      initial eigenmodes with conserved quasiparticle occupation numbers. Based on this
      result, we demonstrate that shortcuts to adiabaticity for the rapid expansion or
      compression of the gas do not induce additional heating. 

PMID- 25867641
TI  - Efficient derivation of retinal pigment epithelium cells from stem cells.
AB  - No cure has been discovered for age-related macular degeneration (AMD), the
      leading cause of vision loss in people over the age of 55. AMD is complex
      multifactorial disease with an unknown etiology, although it is largely thought
      to occur due to death or dysfunction of the retinal pigment epithelium (RPE), a
      monolayer of cells that underlies the retina and provides critical support for
      photoreceptors. RPE cell replacement strategies may hold great promise for
      providing therapeutic relief for a large subset of AMD patients, and RPE cells
      that strongly resemble primary human cells (hRPE) have been generated in multiple
      independent labs, including our own. In addition, the uses for iPS-RPE are not
      limited to cell-based therapies, but also have been used to model RPE diseases.
      These types of studies may not only elucidate the molecular bases of the
      diseases, but also serve as invaluable tools for developing and testing novel
      drugs. We present here an optimized protocol for directed differentiation of RPE
      from stem cells. Adding nicotinamide and either Activin A or IDE-1, a small
      molecule that mimics its effects, at specific time points, greatly enhances the
      yield of RPE cells. Using this technique we can derive large numbers of low
      passage RPE in as early as three months. 

PMID- 25867642
TI  - A Pilot Study of a Group-Based HIV and STI Prevention Intervention for Lesbian,
      Bisexual, Queer, and Other Women Who Have Sex with Women in Canada.
AB  - Limited research has evaluated interventions to reduce HIV and sexually
      transmitted infection (STI) vulnerability among lesbian, bisexual, and queer
      (LBQ) women, and other women who have sex with women. The Queer Women
      Conversations (QWC) study examined the effectiveness of a group-based psycho
      educational HIV/STI intervention with LBQ women in Toronto and Calgary, Canada.
      We conducted a nonrandomized cohort pilot study. Participants completed a pre
      test, post-test, and 6-week follow-up. The primary outcome was sexual risk
      practices, while secondary objectives included intrapersonal (self-esteem, STI
      knowledge, resilient coping, depression), interpersonal (safer sex self
      efficacy), community (community connectedness, social support), and structural
      (sexual stigma, access to healthcare) factors. The study was registered at
      http://clinicaltrials.gov. Forty-four women (mean age 28.7 years) participated in
      a weekend retreat consisting of six consecutive sessions tailored for LBQ women.
      Sessions covered a range of topics addressing behavioral and social-structural
      determinants of HIV/STI risk, including STI information, safer sex negotiation
      skills, and addressing sexual stigma. Adjusted for socio-demographic
      characteristics, sexual risk practices (beta2=-2.96, 95% CI -4.43, -1.50),
      barrier use self-efficacy (beta2=1.52, 95% CI 0.51, 2.53), STI knowledge
      (beta2=4.41, 95% CI 3.52, 5.30), and sexual stigma (beta2=-2.62, 95% CI -3.48, 
      1.75) scores showed statistically significant changes 6 weeks post-intervention.
      Initial increases in safer sex self-efficacy, social support, and community
      connectedness were not sustained at 6-week follow up, highlighting the need for
      booster sessions or alternative approaches to address social factors. Study
      results may inform HIV/STI prevention interventions, sexual health care
      provision, and support services tailored for LBQ women.

PMID- 25867643
TI  - The Future of Anesthesiology: Should the Perioperative Surgical Home Redefine Us?

PMID- 25867644
TI  - Expression of hepatic cytochrome P450 in a mouse model of ulcerative colitis
      changes with pathological conditions.
AB  - BACKGROUND AND AIM: The expression levels of cytochrome P450 (CYP) in the liver
      were analyzed over time in dextran sulfate sodium (DSS)-induced ulcerative
      colitis mouse model, from the initial active stage to the remission stage, to
      investigate the relationship between the changes in pathological conditions and
      CYP expression levels. METHODS: DSS solution was given to mice for 10 days, after
      which water without DSS was provided for 40 days. Pathological conditions and CYP
      expression levels were examined over time. The mechanism for variation in CYP
      expression was also analyzed. RESULTS: The mRNA expression levels of CYP
      (CYP3A11, CYP1A2, CYP2C29, CYP2D9, and CYP2E1) decreased as pathological
      conditions worsened and reached their lowest levels on day 10 of DSS treatment.
      Pathological conditions improved following the discontinuation of DSS, and CYP
      expression levels normalized by day 50. Blood lipopolysaccharide levels, the
      hepatic expression of inflammatory cytokines, and the nuclear translocation of
      pregnane X receptor and constitutive androstane receptor in the liver exhibited
      patterns similar to the observed variations in CYP expression levels. CONCLUSION:
      The capacity for metabolizing drugs that are substrates of CYP decreases during
      the active stage of ulcerative colitis but subsequently improves during the
      remission stage. This decrease in CYP expression was likely caused by the
      observed reduction in the levels of nuclearly localized pregnane X receptor and
      constitutive androstane receptor, and the increase in the production of
      inflammatory cytokines triggered by lipopolysaccharides.

PMID- 25867646
TI  - Second haploidentical peripheral blood stem cell transplantation for treatment of
      acute leukemia with relapse after first allogeneic peripheral blood stem cell
      transplantation.

PMID- 25867645
TI  - Impact of ABO blood group mismatch in alemtuzumab-based reduced-intensity
      conditioned haematopoietic SCT.
AB  - The impact of ABO incompatibility on clinical outcomes following haematopoietic
      SCT (HSCT) remains controversial. This retrospective study assessed the effect of
      ABO mismatch on transplant outcomes and transfusion requirements in 594 patients
      undergoing reduced-intensity conditioned (RIC) HSCT with alemtuzumab in three UK
      transplant centres. We found no significant effects of minor, major or
      bidirectional ABO mismatch on overall survival, relapse-free survival, nonrelapse
      mortality or relapse incidence. Although the rate of acute GVHD was unaffected by
      ABO mismatch, the incidence of extensive chronic GVHD was higher in patients with
      minor and major mismatch compared with those who were ABO matched (hazard ratio
      (HR) 1.74, P=0.032 for minor, HR 1.69 P=0.0036 for major mismatch). Red cell and
      platelet transfusion requirements in the first 100 days post transplant did not
      differ by ABO mismatch. In this large UK series, ABO mismatch in RIC HSCT has no
      clinically significant effect on survival outcomes but appears to modify
      susceptibility to extensive chronic GVHD. 

PMID- 25867647
TI  - High-dose therapy and autologous hematopoietic cell transplantation as front-line
      consolidation in chronic lymphocytic leukemia: a systematic review.
AB  - High-dose therapy (HDT) followed by autologous hematopoietic cell transplantation
      (auto-HCT) is offered to patients with chronic lymphocytic leukemia (CLL) both as
      front-line consolidation and in the relapsed setting. The role of HDT in the
      front-line consolidation setting in CLL is uncertain. Literature search of PUBMED
      and Cochrane until 14 November 2014 and the last 2 years of abstracts from
      relevant conferences was undertaken. End points included benefits (overall
      survival; OS, PFS, event-free survival; EFS) and harms (adverse events, secondary
      malignancies, treatment-related mortality). The search identified 495 references
      of which four studies met inclusion criteria. Altogether, 301 patients were
      randomized to the HDT/auto-HCT arm and 299 patients to the control arm. Offering
      front-line HDT/auto-HCT did not result in statistically significant improvement
      in OS (Hazard ratio (HR)=0.91; 95% confidence interval (CI)= 0.62, 1.33) or PFS
      (HR=0.70; 95% CI= 0.32, 1.52). There was a statistically significant advantage
      favoring HDT/auto-HCT for EFS (HR=0.46; 95% CI= 0.26, 0.83). Moreover, HDT/auto
      HCT did not result in higher rate of secondary malignancy (risk ratio=1.06; 95%
      CI=0.55, 2.05) or treatment-related mortality (risk ratio=1.32; 95% CI= 0.43,
      4.06). Offering HDT/auto-HCT as front-line consolidation in patients with CLL
      does not improve OS. At present this approach should not be offered outside the
      context of a clinical trial. 

PMID- 25867648
TI  - Leukemia cell mobilization with G-CSF plus plerixafor during busulfan-fludarabine
      conditioning for allogeneic stem cell transplantation.
AB  - We hypothesized that during conditioning chemotherapy for allogeneic stem cell
      transplant (allo-SCT), the disruption of stromal-leukemia interactions using G
      CSF in combination with the CXCR4-specific inhibitor, plerixafor, may promote the
      release of leukemic cells from the niche and increase tumor elimination. In a
      phase 1/2 investigation, we treated 45 AML/myelodysplastic syndrome (MDS)/CML
      patients (34 AML, 7 MDS and 4 CML) with G-CSF (10 MUg/kg daily for 6 days
      starting on day -9) plus plerixafor (doses of 0, 80, 160 or 240 MUg/kg daily for
      4 days starting on day -7) along with the busulfan-fludarabine (Bu-Flu)
      conditioning regimen. In the phase 1 part, we determined that G-CSF plus
      plerixafor is safe in this setting. We compared the clinical effects and outcomes
      of AML/MDS study patients (n=40) with 164 patients from a historical data set who
      received Bu-Flu alone before allo-SCT by stratifying on cytogenetics and disease
      status to correct for bias. Study patients had increased myeloid chimerism and
      lower rates of GvHD. There was no significant difference in relapse-free survival
      or overall survival. The G-CSF plus plerixafor combination increased circulating
      WBCs, CD34+ cells and CXCR4+ cells, and preferentially mobilized FISH+ leukemic
      cells.

PMID- 25867649
TI  - JC polyomavirus reactivation is common following allogeneic stem cell
      transplantation and its preemptive detection may prevent lethal complications.
AB  - Extended application of allogeneic stem cell transplantation (alloSCT) is
      expected to increase the frequency of JC polyomavirus (JCPyV)-related progressive
      multifocal leukoencephalopathy (PML). The aim of this study was to assess
      frequency, risk factors and course of JCPyV reactivation in allografted
      hematology patients. This retrospective study included consecutive adult
      patients, treated with alloSCT between January 2008 and December 2011.
      Quantitative JCPyV-PCR analysis was performed on whole blood DNA samples,
      originally drawn for cytomegalovirus detection since transplant date. The study
      included 164 patients diagnosed with hematological malignancies. Patients
      received reduced-intensity conditioning (n=74) or myeloablative conditioning
      (n=90), followed by alloSCT. Twenty patients developed transient and 20 had
      persistent JCPyV reactivation. Two of the patients with persistent reactivation
      showed a gradual increase in JCPyV levels, preceding PML development by 96 and
      127 days. Cessation of immunosuppression resulted in complete resolution of
      neurological symptoms in one patient, while the other died of PML. Seventy
      percent of the 'persistently reactivating' patients died. Multivariate analysis
      confirmed age to be the only significant predictive factor for JCPyV
      reactivation. In conclusion, JCPyV reactivation occurs in a quarter of
      allografted patients. Preemptive detection of JCPyV reactivation in high-risk
      subjects and early discontinuation of immunosuppressive therapy may prevent
      development of lethal PML. 

PMID- 25867650
TI  - Outcomes for HIV-positive patients with primary central nervous system lymphoma
      after high-dose chemotherapy and auto-SCT.

PMID- 25867651
TI  - Safety of outpatient autologous hematopoietic cell transplantation for multiple
      myeloma and lymphoma.
AB  - Autologous hematopoietic cell transplantation (Auto-HCT) is commonly an in
      patient procedure. However, Auto-HCT is increasingly being offered on an
      outpatient basis. To better characterize the safety of outpatient Auto-HCT, we
      compared the outcome of 230 patients who underwent Auto-HCT on an in-patient vs
      outpatient basis for myeloma or lymphoma within a single transplant program. All
      outpatient transplants occurred in a cancer center day hospital. Hematopoietic
      recovery occurred earlier in the outpatient cohort, with median time to
      neutrophil recovery of 10 vs 11 days (P<0.001) and median time to platelet
      recovery of 19 vs 20 days (P=0.053). Fifty-one percent of the outpatient cohort
      never required admission, with this percentage increasing in later years. Grade 3
      4 non-hematologic toxicities occurred in 29% of both cohorts. Non-relapse
      mortality at 1 year was 0% in the outpatient cohort and 1.5% in the in-patient
      cohort (P=0.327). Two-year PFS was 62% for outpatient vs 54% for in-patient
      (P=0.155). One- and two-year OS was 97% and 83% for outpatient vs 91% and 80% for
      in-patient, respectively (P=0.271). We conclude that, with daily outpatient
      evaluation and aggressive supportive care, outpatient Auto-HCT can result in
      excellent outcomes for myeloma and lymphoma patients. 

PMID- 25867652
TI  - Long-term persistence of the immune response to antipneumococcal vaccines after
      Allo-SCT: 10-year follow-up of the EBMT-IDWP01 trial.
AB  - The guidelines for immunization of hematopoietic SCT (HSCT) recipients recommend
      three doses of antipneumococcal conjugate vaccine (PCV) from 3 to 6 months after
      transplant, followed by a dose of polysaccharide 23-valent (PPV23) vaccine at 12
      months in the case of no GVHD or an additional PCV dose in the case of GVHD. Due
      to the lack of long-term data in the literature, there is no recommendation for
      boosts after 12 months. Our goal was to assess the maintenance of the immune
      response to pneumococcal vaccines in patients vaccinated 10 years ago according
      to current guidelines. Thirty surviving patients of the IDWP01 (Infectious
      Diseases Working Party 1) trial were assessed for antibody levels against the
      seven antigens of the PCV7 and against two of the PPV23-specific antigens. When
      compared with 24 months after transplant, the immune response did not
      significantly decrease but with important serotype-specific variability. There
      was no evidence that an additional dose of PPV23 given to 11/30 patients 2-11
      years after transplant was beneficial. In long-term HSCT survivors with no or few
      GVHD vaccinated against Streptococcus pneumoniae according to the current
      guidelines, the specific immunity is not fully maintained a decade later. The
      optimal schedule of antipneumococcal vaccination in HSCT recipients after 12
      months remains to be established. 

PMID- 25867653
TI  - The importance of long-term follow-up in pediatric hematopoietic stem cell
      transplantation.

PMID- 25867654
TI  - Autologous stem cell transplantation versus novel drugs or conventional
      chemotherapy for patients with relapsed multiple myeloma after previous ASCT.
AB  - High-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT)
      is the most common first-line treatment for patients with multiple myeloma (MM)
      under 65 years of age. A second ASCT at first relapse is frequently used but is
      challenged by the use of novel drugs. We retrospectively studied the outcome of
      second-line treatment in MM patients from the Nordic countries with relapse after
      first-line HDT and ASCT. Patients that underwent a second ASCT (n=111) were
      compared with patients re-treated with conventional cytotoxic drugs only (n=91)
      or with regimens including novel drugs (proteasome inhibitors and/or
      immunomodulatory drugs) (n=362) without a second ASCT. For patients receiving a
      second ASCT median overall survival was 4.0 years compared with 3.3 years
      (P<0.001) for the group treated with novel drugs and 2.5 years (P<0.001) for
      those receiving conventional cytotoxic drugs only. A second ASCT also resulted in
      a significantly longer second time to progression and a significantly longer time
      to next treatment. We conclude that, irrespective of the addition of novel drugs,
      MM patients in first relapse after ASCT still appear to benefit from a second
      ASCT. A second ASCT should be considered for all physically fit patients. 

PMID- 25867655
TI  - Collimation and Image Quality of C-Arm Computed Tomography: Potential of
      Radiation Dose Reduction While Maintaining Equal Image Quality.
AB  - OBJECTIVES: The aim of this study was to assess the potential for radiation dose
      reduction in collimated C-arm computed tomography (CACT) while maintaining the
      image quality of the full field of view (FFOV) acquisition. MATERIAL AND METHODS:
      A whole-body anthropomorphic phantom representing a 70-kg male was used in this
      study. The upper abdomen of the phantom was imaged using an angiographic system
      (Artis Zeego Q; Siemens Healthcare, Germany) with either the standard detector
      radiation dose level (RDL; D100, 360 nGy) or 14 experimental reduced RDLs ranging
      from 95% (D95, 342 nGy) to 30% D100 (D30, 108 nGy). Either the FFOV (craniocaudal
      coverage, 18 cm) or a collimated field of view (CFOV; craniocaudal coverage, 6
      cm) was applied. The organ dose was measured using thermoluminescence detector
      dosimetry, and the mean effective dose was computed according to the
      recommendations by the International Commission on Radiological Protection
      Publication 103. To compare the CFOV and the FFOV data sets, image quality was
      assessed in terms of high- and low-contrast resolution by calculating the
      modulation transfer function using the wire method as well as the image noise,
      signal-to-noise ratio, and contrast-to-noise ratio using a low-contrast insert
      placed in the upper abdomen (Delta50 HU). RESULTS: Collimated imaging (CFOV)
      covering 33% of the FFOV led to an increase in the x-ray tube output of 152% for
      CFOV (D100; FFOV, 95.5 mGy; CFOV, 147.7 mGy) to maintain the detector dose. The
      mean effective dose of D100 was 6.0 mSv (male) and 6.2 mSv (female) for the FFOV
      and 3.7 mSv (male) and 4.1 mSv (female) for the CFOV. High-contrast resolution
      was comparable for all acquisition protocols (mean 10% modulation transfer
      function +/- 95% confidence interval; FFOV, 8.8 +/- 0.1 line pairs/cm; CFOV, 8.8
      +/- 0.1 line pairs/cm). Low-contrast resolution was superior for the CFOV
      compared with that for the FFOV for each RDL (D100; image noise: FFOV, 34 +/- 2
      HU; CFOV, 22 +/- 1 HU; contrast-to-noise ratio: FFOV, 1.3 +/- 0.2; CFOV, 1.8 +/-
      0.3). Low-contrast resolution of the standard (D100) FFOV acquisition was
      achieved for the CFOV at 84% D100 of the FFOV and 54% D100 of the CFOV.
      Therefore, collimation up to 33% of the FFOV combined with the lower detector
      dose allows overall reduction of a patient's radiation exposure to 33% * 84% =
      28% compared with FFOV acquisition. In the upper abdomen, this results in a
      nearly 50% reduction of the mean effective radiation dose (male, 2.0 mSv; female,
      2.2 mSv) without loss of image quality compared with the standard FFOV
      acquisition. CONCLUSIONS: Craniocaudal collimation in CACT should be used
      whenever possible to increase the image quality and reduce the patient's overall
      radiation exposure. Therefore, new smart acquisition protocols are required for
      collimated CACT to improve the trade-off between radiation exposure and image
      quality requirements considering the collimation used.

PMID- 25867656
TI  - Multiparametric Magnetic Resonance Imaging for Discriminating Low-Grade From High
      Grade Prostate Cancer.
AB  - OBJECTIVE: The aim of this study was to determine and validate the optimal
      combination of parameters derived from 3-T diffusion-weighted imaging, dynamic
      contrast-enhanced imaging, and magnetic resonance (MR) spectroscopic imaging for
      discriminating low-grade from high-grade prostate cancer (PCa). MATERIALS AND
      METHODS: The study was approved by the institutional review board, and the need
      for informed consent was waived. Ninety-four patients with PCa who had undergone
      multiparametric MR imaging (MRI) before prostatectomy were included. Cancer was
      indicated on T2-weighted images, blinded to any functional data, with
      prostatectomy specimens as the reference standard. Tumors were classified as low
      grade or high grade based on Gleason score; peripheral zone (PZ) and transition
      zone (TZ) tumors were analyzed separately. In a development set (43 patients),
      the optimal combination of multiparametric MRI parameters was determined using
      logistic regression modeling. Subsequently, this combination was evaluated in a
      separate validation set (51 patients). RESULTS: In the PZ, the 25th percentile of
      apparent diffusion coefficient (ADC) derived from diffusion-weighted imaging and
      washout (WO25) derived from dynamic contrast-enhanced MRI offered the optimal
      combination of parameters. In the TZ, WO25 and the choline over spermine +
      creatine ratio (C/SC) derived from MR spectroscopic imaging showed the highest
      discriminating performance. Using the models built with the development set, 48
      (74%) of 65 cancer lesions were classified correctly in the validation set.
      CONCLUSIONS: Multiparametric MRI is a useful tool for the discrimination between
      low-grade and high-grade PCa and performs better than any individual functional
      parameter in both the PZ and TZ. The 25th percentile of ADC + WO25 offered the
      optimal combination in the PZ, and the choline over spermine + creatine ratio +
      WO25 offered the optimal combination in the TZ. The ADC parameter has no
      additional value for the assessment of PCa aggressiveness in the TZ.

PMID- 25867657
TI  - Evaluation of Diffusion Kurtosis Imaging Versus Standard Diffusion Imaging for
      Detection and Grading of Peripheral Zone Prostate Cancer.
AB  - OBJECTIVES: The purpose of the study was to evaluate and validate diffusion
      kurtosis imaging (DKI) for detection grading of peripheral zone prostate cancer
      (PCa) compared with standard diffusion-weighted imaging (DWI) in a cohort of
      patients with biopsy-proven PCa. MATERIALS AND METHODS: In this retrospective,
      single-institutional study, 55 patients (age, 67.5 +/- 6.9 years; range, 52-84
      years) who underwent multiparametric magnetic resonance imaging (MRI) before
      transperineal magnetic resonance/transrectal ultrasound-guided fusion biopsy were
      included. Suspicious lesions identified in multiparametric MRI underwent image
      guided targeted biopsy procedure using a hybrid magnetic resonance/transrectal
      ultrasound-guided fusion biopsy system. Multiparametric MRI examinations were
      performed at 3.0 T using a 16-channel phased array coil. Diffusion kurtosis
      imaging has been acquired with 9 b values (0, 50, 250, 500, 750, 1000, 1250,
      1500, and 2000 s/mm). In patients with histologically proven PCa, a
      representative tumor region was determined as region of interest (ROI) on axial
      T2-weighted images in consensus by 2 board-certified radiologists. For
      quantitative evaluation, ROIs located in malignant and contralateral tumor-free
      regions were transferred to diffusion-weighted images. Diffusion kurtosis imaging
      parameters (Dapp and Kapp) and apparent diffusion coefficient (ADC) values of the
      ROIs in tumor and contralateral remote areas were calculated. Estimation of the
      kurtosis-derived parameters was performed using a voxel-by-voxel fit followed by
      an ROI-based averaging and a second fit to ROI-averaged signal values. A subgroup
      analysis was performed to determine the influence of aggressiveness of PCa using
      ADC, Dapp, and Kapp. The receiver operating characteristic (ROC) curves were
      calculated for DKI parameters and ADC values. RESULTS: In the 55 patients, the
      average prostate-specific antigen level was 12.4 +/- 12.6 ng/mL (range, 2.7-75.0
      ng/mL), and the median Gleason score was 7 (range, 6-10). Dapp (units, 10(-3)
      mm(2)/s) was significantly lower in tumor compared with control regions (1.48 +/-
      0.35 vs 2.00 +/- 0.32, P < 0.05), and Kapp was significantly higher (1.01 +/-
      0.21 vs 0.76 +/- 0.14, P < 0.05). Dapp was significantly higher than standard ADC
      (units, 10(-3) mm(2)/s) both in tumor regions and in controls (1.48 +/- 0.35 vs
      1.10 +/- 0.25 and 2.00 +/- 0.32 vs 1.43 +/- 0.25, P < 0.05). Neither the ROI
      based calculation of the kurtosis parameters nor the application of the noise
      correction significantly changed the DKI parameter estimation. There was no
      significant difference for the applied fitting method for DKI-derived parameters
      considering the differentiation between tumor and control tissue. Subsequent ROC
      analyses did not reveal a significant difference between DKI and ADC for
      detection of PCa. Sensitivities derived by Youden J statistics cutoff values
      ranged from 69% to 91% for DKI parameters; specificities ranged from 71% to 89%.
      Subgroup analysis for DKI (Dapp, Kapp) and ADC for assessing aggressiveness of
      PCa found significant difference (P < 0.05) for discrimination between high- and
      low-grade findings. However, no significant difference could be obtained between
      standard DWI- and DKI-derived parameters. CONCLUSIONS: The results of this study
      demonstrated no significant benefit of DKI for detection and grading of PCa as
      compared with standard ADC in the peripheral zone determined from b values of 0
      and 800 s/mm. For clinical routine application, ADC derived from monoexponential
      fitting of DWI data remains the standard for characterizing peripheral zone
      cancer of the prostate.

PMID- 25867658
TI  - Efficacy and tolerability of prostaglandin-timolol fixed combinations: an updated
      systematic review and meta-analysis.
AB  - BACKGROUND: Prostaglandin-timolol fixed combinations (PG-timolol FCs) are now
      widely used to reduce intraocular pressure in patients with glaucoma. The
      efficacy and tolerability of these drugs are worthy of further exploration. An
      updated systematic review and meta-analysis was performed to assess the clinical
      efficacy and tolerability of the three PG-timolol FCs. METHODS: Pertinent
      randomized, controlled trials were identified through systematic searches of
      PubMed, Embase, the Cochrane central register of controlled trials and the
      Chinese Biomedicine Database. The main efficacy measures were the weighted mean
      differences (WMDs) for the reduction from baseline to end of treatment in IOP at
      9 am, 12 pm and 4 pm and diurnal curve. The main tolerability measures were the
      odds ratios (ORs) for the incidence of conjunctival hyperemia. RESULTS: Nine
      studies involving 991 patients were included in the meta-analysis. Latanoprost
      timolol FC (LTFC) and travoprost-timolol FC (TTFC) were not significantly
      different in lowering IOP at diurnal mean, 9 am, 12 pm and 4 pm. Bimatoprost
      timolol FC (BTFC) provided significantly greater efficacy in lowering IOP at the
      three measurement time points and over the mean diurnal curve than LTFC (diurnal
      curve: WMD = 0.88 mmHg [95% CI, 0.42 to 1.33]; 9 am: WMD = 1.27 mmHg [0.68 to
      1.86]; 12 pm: WMD = 1.16 mmHg [0.85 to 1.46]; 4 pm: WMD = 0.61 mmHg [0.51 to
      0.70]) and TTFC (diurnal curve: WMD = 1.94 mmHg [0.19 to 3.68]; 9 am: WMD = 0.68
      mmHg [0.15 to 1.21]; 12 pm: WMD = 0.90 mmHg [0.41 to 1.39]; 4 pm: WMD = 1.06 mmHg
      [0.61 to 1.51]). The incidence of hyperemia was significantly higher with BTFC
      than LTFC (pooled ORs: 1.85 [1.09 to 3.13]). The incidence of hyperemia was not
      significantly higher with TTFC than LTFC (pooled ORs: 2.52 [0.85 to 7.46]), and
      was not significantly higher with BTFC than TTFC (pooled OR: 1.65 [0.48 to
      5.70]). CONCLUSIONS: BTFC provided significantly greater efficacy in lowering IOP
      at diurnal mean, 9 am, 12 pm and 4 pm than LTFC and TTFC. LTFC was as effective
      as TTFC in lowering IOP at the four measurement time points and BTFC caused
      conjunctival hyperemia in more patients than LTFC. Further clinical trials are
      needed because of the limited number of studies.

PMID- 25867660
TI  - Effects of Meloxicam on Hematologic and Plasma Biochemical Analyte Values and
      Results of Histologic Examination of Kidney Biopsy Specimens of African Grey
      Parrots (Psittacus erithacus).
AB  - In this study we evaluated the effects of meloxicam administered at 0.5 mg/kg IM
      q12h for 14 days on hematologic and plasma biochemical values and on kidney
      tissue in 11 healthy African grey parrots (Psittacus erithacus). Before treatment
      with meloxicam, blood samples were collected and renal biopsy samples were
      obtained from the cranial portion of the left kidney from each of the birds. On
      day 14 of treatment, a second blood sample and biopsy from the middle portion of
      the left kidney were obtained from each bird. All birds remained clinically
      normal throughout the study period. No significant differences were found between
      hematologic and plasma biochemical values before and after 14 days of treatment
      with meloxicam, except for a slight increase in median beta globulin and
      corresponding total globulin concentrations, and a slight decrease in median
      phosphorus concentration. Renal lesions were absent in 9 of 10 representative
      posttreatment biopsy samples. On the basis of these results, meloxicam
      administered at the dosage used in this study protocol does not appear to cause
      renal disease in African grey parrots. 

PMID- 25867661
TI  - Endoscopic Vasectomy of Male Feral Pigeons (Columba livia) as a Possible Method
      of Population Control.
AB  - To evaluate whether single-entry endoscopic vasectomy of male feral pigeons
      (Columba livia) significantly reduced fertility and would potentially be valuable
      for control of feral pigeon populations, 252 male feral pigeons were caught in
      the city of Berne and endoscopically vasectomized. In this procedure,
      approximately 1 cm of the deferent duct was removed bilaterally. Rapid,
      uneventful recoveries occurred in 94% (237/252) of the pigeons, whereas 6%
      (15/252) died because of complications associated with the procedure, consisting
      of perforation of the ureter (9/15), major hemorrhage (5/15), and respiratory
      arrest (1/15). Mean anesthesia time was 23+/-6 minutes. The vasectomized males
      were habituated to 2 pigeon houses together with fertile females. Another pigeon
      house with fertile pairs acted as control. All eggs laid were candled weekly to
      assess fertility. In the 2 pigeon houses with vasectomized males, the mean
      fertilization rate was 0.9% (5/563), while in the control pigeon house, the rate
      was 100% (39/39). The results indicate that endoscopic vasectomy of male feral
      pigeons may be a promising tool for field control of feral pigeon populations,
      especially in combination with other methods such as pigeon houses.

PMID- 25867659
TI  - Increased Hospital-Based Physical Rehabilitation and Information Provision After
      Intensive Care Unit Discharge: The RECOVER Randomized Clinical Trial.
AB  - IMPORTANCE: Critical illness results in disability and reduced health-related
      quality of life (HRQOL), but the optimum timing and components of rehabilitation
      are uncertain. OBJECTIVE: To evaluate the effect of increasing physical and
      nutritional rehabilitation plus information delivered during the post-intensive
      care unit (ICU) acute hospital stay by dedicated rehabilitation assistants on
      subsequent mobility, HRQOL, and prevalent disabilities. DESIGN, SETTING, AND
      PARTICIPANTS: A parallel group, randomized clinical trial with blinded outcome
      assessment at 2 hospitals in Edinburgh, Scotland, of 240 patients discharged from
      the ICU between December 1, 2010, and January 31, 2013, who required at least 48
      hours of mechanical ventilation. Analysis for the primary outcome and other 3
      month outcomes was performed between June and August 2013; for the 6- and 12
      month outcomes and the health economic evaluation, between March and April 2014.
      INTERVENTIONS: During the post-ICU hospital stay, both groups received
      physiotherapy and dietetic, occupational, and speech/language therapy, but
      patients in the intervention group received rehabilitation that typically
      increased the frequency of mobility and exercise therapies 2- to 3-fold,
      increased dietetic assessment and treatment, used individualized goal setting,
      and provided greater illness-specific information. Intervention group therapy was
      coordinated and delivered by a dedicated rehabilitation practitioner. MAIN
      OUTCOMES AND MEASURES: The Rivermead Mobility Index (RMI) (range 0-15) at 3
      months; higher scores indicate greater mobility. Secondary outcomes included
      HRQOL, psychological outcomes, self-reported symptoms, patient experience, and
      cost-effectiveness during a 12-month follow-up (completed in February 2014).
      RESULTS: Median RMI at randomization was 3 (interquartile range [IQR], 1-6) and
      at 3 months was 13 (IQR, 10-14) for the intervention and usual care groups (mean
      difference, -0.2 [95% CI, -1.3 to 0.9; P = .71]). The HRQOL scores were unchanged
      by the intervention (mean difference in the Physical Component Summary score, 
      0.1 [95% CI, -3.3 to 3.1; P = .96]; and in the Mental Component Summary score,
      0.2 [95% CI, -3.4 to 3.8; P = .91]). No differences were found for self-reported
      symptoms of fatigue, pain, appetite, joint stiffness, or breathlessness. Levels
      of anxiety, depression, and posttraumatic stress were similar, as were hand grip
      strength and the timed Up & Go test. No differences were found at the 6- or 12
      month follow-up for any outcome measures. However, patients in the intervention
      group reported greater satisfaction with physiotherapy, nutritional support,
      coordination of care, and information provision. CONCLUSIONS AND RELEVANCE: Post
      ICU hospital-based rehabilitation, including increased physical and nutritional
      therapy plus information provision, did not improve physical recovery or HRQOL,
      but improved patient satisfaction with many aspects of recovery. TRIAL
      REGISTRATION: isrctn.com Identifier: ISRCTN09412438.

PMID- 25867662
TI  - Plasma Drug Concentrations of Orally Administered Rosuvastatin in Hispaniolan
      Amazon Parrots (Amazona ventralis).
AB  - Atherosclerotic diseases are common in pet psittacine birds, in particular Amazon
      parrots. While hypercholesterolemia and dyslipidemia have not definitely been
      associated with increased susceptibility to atherosclerosis in parrots, these are
      important and well-known risk factors in humans. Therefore statin drugs such as
      rosuvastatin constitute the mainstay of human treatment of dyslipidemia and the
      prevention of atherosclerosis. No pharmacologic studies have been performed in
      psittacine birds despite the high prevalence of atherosclerosis in captivity.
      Thirteen Hispaniolan Amazon parrots were used to test a single oral dose of 10
      mg/kg of rosuvastatin with blood sampling performed according to a balanced
      incomplete block design over 36 hours. Because low plasma concentrations were
      produced in the first study, a subsequent pilot study using a dose of 25 mg/kg in
      2 Amazon parrots was performed. Most plasma samples for the 10 mg/kg dose and all
      samples for the 25 mg/kg dose had rosuvastatin concentration below the limits of
      quantitation. For the 10 mg/kg study, the median peak plasma concentration and
      time to peak plasma concentration were 0.032 MUg/mL and 2 hours, respectively.
      Our results indicate that rosuvastatin does not appear suitable in Amazon parrots
      as compounded and used at the dose in this study. Pharmacodynamic studies
      investigating lipid-lowering effects of statins rather than pharmacokinetic
      studies may be more practical and cost effective in future studies to screen for
      a statin with more ideal properties for potential use in psittacine dyslipidemia
      and atherosclerotic diseases. 

PMID- 25867663
TI  - Evaluation of the phenol red thread tear test in falconiformes.
AB  - Falconiformes are active searchers and hunters that require visual precision to
      catch their prey and survive in the wild. Despite this, ocular disease is likely
      to be underdiagnosed in these species, at least in part because of limited proven
      diagnostic methods and lack of published scientific data. Tear film deficiency is
      recognized as an important ocular surface disease in dogs but has not been well
      evaluated in birds. To evaluate the phenol red thread (PRT) tear test as an
      alternative method to the Schirmer tear test (STT) for determining tear
      production in Falconiformes, we assessed the PRT tear test twice for each eye in
      21 birds from the genus Falco. The mean PRT test values for the right (OD) and
      left (OS) eyes were OD=30.2+/-4.6 mm/15 s and OS=29.1+/-3.7 mm/15 s, with an
      overall PRT test value for both eyes (OU) of 30.6+/-4.2 mm/15 s. Good
      reproducibility was seen with the PRT test as shown by the strong positive
      correlation between the first and second tests in the birds. The PRT test method
      provides repeatable results that are easy to obtain, easy to read, and achieved
      under the same conditions as the STT.

PMID- 25867664
TI  - Effectiveness of Physical Therapy as an Adjunctive Treatment for Trauma-induced
      Chronic Torticollis in Raptors.
AB  - Management of trauma-induced chronic torticollis in raptors has historically been
      challenging. Euthanasia is common in affected birds because of their inability to
      maintain normal cervical position, although they may be able to function
      normally. To assess effectiveness of physical therapy of the neck and head as an
      adjunct treatment for this condition, a case-control study was done in raptors
      admitted to the Rocky Mountain Raptor Program from 2003 to 2010. Eleven cases
      were identified with a diagnosis of chronic torticollis resulting from traumatic
      brain injury. Five cases were treated with physical therapy of the head and neck,
      and 6 control cases did not receive any physical therapy for the torticollis. Of
      the control cases, 0 of 6 had resolution of the torticollis, 0 of 6 were
      released, and 5 of 6 were euthanatized. Of the treated cases, 4 of 5 had complete
      resolution of the torticollis and 5 of 5 were released. Resolution of torticollis
      differed significantly between cases receiving physical therapy and controls.
      These results indicate that physical therapy should be used as an adjunctive
      therapy in cases of chronic torticollis induced by trauma in raptors because it
      results in better resolution of the torticollis and increased likelihood of
      release. 

PMID- 25867665
TI  - Diagnosis of Retrobulbar Round Cell Neoplasia in a Macaroni Penguin ( Eudyptes
      chrysolophus ) Through Use of Computed Tomography.
AB  - A 25-year-old female macaroni penguin (Eudyptes chrysolophus) was diagnosed with
      exophthalmos secondary to retrobulbar neoplasia through use of computed
      tomography (CT). Histopathologic examination of the mass supported a diagnosis of
      malignant round cell neoplasia. Immunohistochemical (IHC) labeling was applied to
      determine cell origin; the neoplastic cells did not label with T-cell marker CD3
      or B-cell marker BLA.36 and could not be further characterized. The scleral
      ossicles precluded evaluation of the retrobulbar space by ultrasonography;
      therefore, CT scanning is recommended for examination of intraorbital structures
      in penguin and other avian species.

PMID- 25867666
TI  - Bilateral Renal Tubular Neoplasm in a Channel-billed Toucan (Ramphastos
      vitellinus).
AB  - An adult male channel-billed toucan (Ramphastos vitellinus) was presented with a
      history of weakness, dyspnea, and severe dilatation of the coelomic cavity, which
      was caused by accumulation of serohemorrhagic fluid. Radiographs revealed
      increased radiodensity and thickness of the descending aorta and a pectoral mass,
      and blood test results revealed anemia, hypocalcemia, hypoproteinemia, and
      hyperuricemia. On ultrasound examination, a hyperechoic enlarged soft tissue mass
      was found in the caudodorsal region of the coelom. The bird did not respond to
      supportive care and died. Postmortem examination revealed severe, bilateral
      nephromegaly due to multifocal to coalescing renal tubular adenomas
      (adenomatosis), which was complicated with renal gout and soft tissue
      mineralization. Relevant concurrent diseases included hepatic hemochromatosis,
      subcutaneous cestodiasis with cellulitis, and systemic amyloidosis. There are few
      documented cases of neoplasms in ramphastid birds and to our knowledge, this is
      the first report of a renal neoplasm in a channel-billed toucan. 

PMID- 25867667
TI  - Long-term Management of Thymic Lymphoma in a Java Sparrow (Lonchura oryzivora).
AB  - A 4-year-old Java sparrow (Lonchura oryzivora) was diagnosed with thymic lymphoma
      based on the results of histopathologic evaluation and immunohistochemical
      staining of a Tru-cut biopsy sample. The bird was treated with chlorambucil (2
      mg/kg PO) twice per week for the first 18 weeks, and the mass size, activity
      level, appetite, bowel function, and body weight were monitored weekly. At week
      19, the bird became ill and anorexic, and the chlorambucil treatment was
      discontinued. The neoplasm grew rapidly during weeks 20 and 21, and the
      chlorambucil treatment was resumed at week 23. At week 28, the bird's overall
      condition worsened and the chlorambucil treatment was discontinued because no
      additional reduction in mass size had occurred. At week 29, prednisolone (2.2
      mg/kg) was administered orally every 12 h for 31 weeks. At week 61, the patient
      became acutely ill, exhibiting anorexia and a decreased level of physical
      activity, and the owner elected to euthanatize the bird. This is the first report
      of long-term management of thymic lymphoma in a Java sparrow. 

PMID- 25867668
TI  - Pericardial Mesothelioma in a Yellow-naped Amazon Parrot (Amazona auropalliata).
AB  - A 37-year-old female yellow-naped Amazon parrot (Amazona auropalliata) was
      presented with a history of lethargy, inappetence, and decreased vocalizations.
      On examination, the coelom was moderately distended and palpated fluctuant, and
      the heart was muffled on auscultation. Coelomic ultrasound, coelomocentesis, and
      radiographs were performed and revealed an enlarged cardiac silhouette and marked
      coelomic effusion. Pericardial effusion was confirmed by echocardiography. A well
      circumscribed, hyperechoic soft tissue density was observed at the level of the
      right atrium on initial echocardiography; however, a cardiac mass was not
      identified by computed tomography scan or repeat echocardiograms. Ultrasound
      guided pericardiocentesis was performed under anesthesia, and cytology results
      were consistent with hemorrhage; no neoplastic cells were identified. A repeat
      echocardiogram 4 days after pericardiocentesis revealed recurrence of the
      pericardial effusion. Due to the grave prognosis, the owners declined endoscopic
      pericardiectomy, and the patient died the following day. On postmortem
      examination, the pericardial surface of the heart was covered in a white to
      yellow, multinodular mass layer. Histologic analysis revealed a multinodular mass
      extending from the atria, running along the epicardium distally, and often
      extending into the myocardium. Neoplastic cells present in the heart mass and
      pericardium did not stain with a Churukian-Schenk stain, and thyroglobulin
      immunohistochemistry was negative. Cytokeratin and vimentin stains showed
      positive expression in the neoplastic cells within the mass. These results are
      consistent with a diagnosis of mesothelioma. This is the first report of
      mesothelioma in a psittacine bird.

PMID- 25867669
TI  - Ileo-ceco-rectal Intussusception Requiring Intestinal Resection and Anastomosis
      in a Tawny Eagle (Aquila rapax).
AB  - A 23-year-old male tawny eagle (Aquila rapax) was examined because of sudden
      onset of lethargy, regurgitation, and hematochezia. An intestinal obstruction was
      suspected based on radiographic findings, and an ileo-ceco-rectal intussusception
      was confirmed by coelioscopy. A 14.3-cm section of intestine was resected before
      an intestinal anastomosis was done. Coelomic endoscopic examination confirmed a
      postsurgical complication of adhesions between the intestinal anastomosis and the
      dorsal coelomic wall, resulting in a partial luminal stricture and requiring
      surgical removal of the adhesions. Rectoscopy was useful in diagnosing a mild
      luminal stricture related to the second surgery. Complete recovery was observed 2
      months after surgery. Lack of further complications in the 2 years after surgery
      demonstrates good tolerance of intestinal resection and anastomosis of a large
      segment of bowel in an eagle. This report is the first reported case of
      intussusception in an eagle and emphasizes the potential use of endoscopic
      examination in the diagnosis as well as in the management of complications. 

PMID- 25867670
TI  - Therapeutic laser treatment for exotic animal patients.

PMID- 25867671
TI  - What is your diagnosis? Cardiovascular distress secondary to pericardial
      effusion.

PMID- 25867674
TI  - Amine detection with distyrylbenzenedialdehyde-based Knoevenagel adducts.
AB  - Eight acceptor-substituted distyrylbenzene (DSB) derivatives were obtained by
      postfunctionalization of dialdehyde precursor 1 using Knoevenagel condensation.
      Solubility in a water/THF 9:1 mixture was achieved through the addition of
      branched oligoethylene glycol side chains. The acceptor compounds discriminate
      primary and secondary amines in aqueous solution. The fluorescence responses were
      analyzed by the multivariate analysis of variance (MANOVA) protocol, a
      statistical tool. In contrast to 1, the adducts show reactivity toward secondary
      and aromatic amines. Nitroolefin 2f is the most active dosimeter molecule.
      Reaction with amines is completed after less than 3 min, and the limit of
      detection (LOD) is improved by a factor of 10. Propylenediamine can be detected
      at 75 MUM. This is a 10-fold improvement for the detection limit when compared to
      the detection limit of the starting dialdehyde. 

PMID- 25867675
TI  - Transferability and generalizability of regression models of ultrafine particles
      in urban neighborhoods in the Boston area.
AB  - Land use regression (LUR) models have been used to assess air pollutant exposure,
      but limited evidence exists on whether location-specific LUR models are
      applicable to other locations (transferability) or general models are applicable
      to smaller areas (generalizability). We tested transferability and
      generalizability of spatial-temporal LUR models of hourly particle number
      concentration (PNC) for Boston-area (MA, U.S.A.) urban neighborhoods near
      Interstate 93. Four neighborhood-specific regression models and one Boston-area
      model were developed from mobile monitoring measurements (34-46 days/neighborhood
      over one year each). Transferability was tested by applying each neighborhood
      specific model to the other neighborhoods; generalizability was tested by
      applying the Boston-area model to each neighborhood. Both the transferability and
      generalizability of models were tested with and without neighborhood-specific
      calibration. Important PNC predictors (adjusted-R(2) = 0.24-0.43) included wind
      speed and direction, temperature, highway traffic volume, and distance from the
      highway edge. Direct model transferability was poor (R(2) < 0.17). Locally
      calibrated transferred models (R(2) = 0.19-0.40) and the Boston-area model
      (adjusted-R(2) = 0.26, range: 0.13-0.30) performed similarly to neighborhood
      specific models; however, some coefficients of locally calibrated transferred
      models were uninterpretable. Our results show that transferability of
      neighborhood-specific LUR models of hourly PNC was limited, but that a general
      model performed acceptably in multiple areas when calibrated with local data. 

PMID- 25867676
TI  - A public goods approach to major evolutionary innovations.
AB  - The history of life is marked by a small number of major transitions, whether
      viewed from a genetic, ecological, or geological perspective. Specialists from
      various disciplines have focused on the packaging of information to generate new
      evolutionary individuals, on the expansion of ecological opportunity, or the
      abiotic drivers of environmental change to which organisms respond as the major
      drivers of these episodes. But the critical issue for understanding these major
      evolutionary transitions (METs) lies in the interactions between environmental,
      ecologic, and genetic change. Here, I propose that public goods may serve as one
      currency of such interactions: biological products that are non-excludable and
      non-rivalrous. Such biological public goods may be involved in either the
      generation of new evolutionary variation, as with genetic sequences that are
      easily transferred between different microbial lineages, or in the construction
      of new ecological niches, as with the progressive oxygenation of the oceans and
      atmosphere. Attention to public goods emphasizes the processes by which organisms
      actively construct their own evolutionary opportunities. Such public goods may
      have facilitated some METs. 

PMID- 25867678
TI  - Nonfunctionalized Gold Nanoparticles: Synthetic Routes and Synthesis Condition
      Dependence.
AB  - Since Faraday first described gold sol synthesis, synthetic routes to
      nanoparticles, as well as their applications, have experienced a huge growth.
      Variations in synthesis conditions such as pH, temperature, reduction, and the
      stabilizing agent used will determine the morphology, size, monodispersity, and
      stability of nanoparticles obtained, allowing for modulation of their physical
      and chemical properties. Although many studies have been made about the synthesis
      and characterization of individual nanosystems of interest, to our knowledge the
      common, general traits that all those synthesis share have not been previously
      compiled. In this review, we aim to offer a global vision of some of the most
      relevant synthetic procedures reported up to date, with a special focus on
      nonfunctionalized gold nanoparticle synthetic routes in aqueous media, and to
      display a broad overview of the influence that synthesis conditions have on the
      shape, stability, and reactivity of nanoparticle systems. 

PMID- 25867679
TI  - Ferrocene functionalized nanoscale mixed-oxides as a potent phosphate adsorbent
      from the synthetic and real (Persian Gulf) waters.
AB  - The application of covalently attached ferrocene groups to the aluminum-silicate
      nanoparticles (ASNPs) for phosphate (P) removal from the synthetic and real
      waters has been studied and the prepared nanomaterials were analyzed by XPS, EDS,
      BET, TEM, chemical analysis (CHN), FTIR, and ICP-AES. The immobilization of the
      ferrocene on the surface of the inorganic support (mixed oxides) can lead to
      reduce the drawback of the pristine ferrocene molecules which may have strong
      tendency to agglomerate into larger particles, resulting in the negative effect
      on both available active sites and catalyst performance. XPS of Fe ions evidenced
      that most of the active sites of the nano-adsorbent is in the form of Fe(III)
      ions at the surface. The heterogeneous Fe(III) ions were effective toward removal
      of phosphate. The contact time to obtain equilibrium for maximum adsorption of
      phosphate (100%) was found to be 120 min. The adsorption kinetics of P has been
      evaluated in terms of pseudo-first- and -second-order kinetics, and the
      Freundlich and Langmuir isotherm models have also been tested to the equilibrium
      adsorption results. The adsorption process was spontaneous and endothermic in
      nature and followed pseudo-second-order kinetic model. FTIR, EDS and XPS results
      confirmed the formation of Fe-O-P bond on the Si/Al@Fe surface after adsorption
      of P from aqueous media. The Si/Al@Fe displayed high reusability due to its high
      removal capacity after 10th adsorption-desorption runs. The proposed adsorbent
      could also be utilized to adsorb the P ions from the real sample (Persian Gulf
      water). The high removal capacity of P ions from the real water and the high
      levels of reusability confirmed the versatility of the heterogenized ferrocene
      groups on the ASNPs.

PMID- 25867677
TI  - Cerebrospinal Fluid Markers of Neurodegeneration and Rates of Brain Atrophy in
      Early Alzheimer Disease.
AB  - IMPORTANCE: Measures of neuronal loss are likely good surrogates for clinical and
      radiological disease progression in Alzheimer disease (AD). Cerebrospinal fluid
      (CSF) markers of neuronal injury or neurodegeneration may offer usefulness in
      predicting disease progression and guiding outcome assessments and prognostic
      decisions in clinical trials of disease-modifying therapies. Visinin-like protein
      1 (VILIP-1) has demonstrated potential usefulness as a marker of neuronal injury
      in AD. OBJECTIVE: To investigate the usefulness of CSF VILIP-1, tau, p-tau181,
      and Abeta42 levels in predicting rates of whole-brain and regional atrophy in
      early AD and cognitively normal control subjects over time. DESIGN, SETTING, AND
      PARTICIPANTS: Longitudinal observational study of brain atrophy in participants
      with early AD and cognitively normal controls. Study participants had baseline
      CSF biomarker measurements and longitudinal magnetic resonance imaging
      assessments for a mean follow-up period of 2 to 3 years. Mixed linear models
      assessed the ability of standardized baseline CSF biomarker measures to predict
      rates of whole-brain and regional atrophy over the follow-up period. The setting
      was The Charles F. and Joanne Knight Alzheimer's Disease Research Center,
      Washington University School of Medicine in St Louis. Participants (mean age,
      72.6 years) were individuals with a clinical diagnosis of very mild AD (n = 23)
      and cognitively normal controls (n = 64) who were enrolled in longitudinal
      studies of healthy aging and dementia. The study dates were 2000 to 2010. MAIN
      OUTCOMES AND MEASURES: Correlations between baseline CSF biomarker measures and
      rates of whole-brain or regional atrophy in the AD and control cohorts over the
      follow-up period. RESULTS: Baseline CSF VILIP-1, tau, and p-tau181 levels (but
      not Abeta42 levels) predicted rates of whole-brain and regional atrophy in AD
      over the follow-up period. Baseline CSF VILIP-1 levels predicted whole-brain (P =
      .006), hippocampal (P = .01), and entorhinal (P = .001) atrophy rates at least as
      well as tau and p-tau181 in early AD. Cognitively normal controls whose CSF VILIP
      1, tau, or p-tau181 levels were in the upper tercile had higher rates of whole
      brain (P = .02, P = .003, and P = .02, respectively), hippocampal (P = .001, P =
      .01, and P = .02, respectively), and entorhinal (P = .007, P = .01, and P = .01,
      respectively) atrophy compared with those whose levels were in the lower 2
      terciles. CONCLUSIONS AND RELEVANCE: Cerebrospinal fluid VILIP-1 levels predict
      rates of whole-brain and regional atrophy similarly to tau and p-tau181 and may
      provide a useful CSF biomarker surrogate for neurodegeneration in early
      symptomatic and preclinical AD.

PMID- 25867680
TI  - Effect of sodium dodecylsulfate monomers and micelles on the stability of aqueous
      dispersions of titanium dioxide pigment nanoparticles against agglomeration and
      sedimentation.
AB  - HYPOTHESIS: As more sodium dodecylsulfate (SDS) monomers adsorb at the
      water/titanium dioxide (TiO2) nanoparticles interface, the particles become more
      stable against agglomeration and sediment more slowly. SDS micelles are not
      expected to adsorb on the particles and affect the stability against
      agglomeration or sedimentation. Since micelles are smaller than the 300 nm TiO2
      nanoparticles studied, they may introduce depletion forces which may affect the
      dispersion stability. EXPERIMENTS AND MODELS: Sedimentation times were measured
      in water and in 100 mM NaCl for SDS concentrations from 0.1 to 200 mM. Adsorption
      densities of SDS and zeta potentials of particles were measured. Dynamic light
      scattering was used to measure average diameters of particles or particle
      agglomerates. Modeling of sedimentation/diffusion was done to predict
      sedimentation times of particles. Modeling of agglomeration rates was done to
      help predict sedimentation rates of clusters. FINDINGS: At SDS concentrations
      close to or above the cmc, up to 60 mM in water or 115 mM in 100 mM NaCl, the
      nanoparticles sediment most slowly without any agglomeration. At higher micelle
      concentration, SDS micelle depletion forces are very strong, causing fast
      flocculation, without coagulation. Then sedimentation occurs much faster. The
      effective micelle depletant size includes about 4 Debye lengths of the charged
      micelles or particles.

PMID- 25867682
TI  - Capture compound mass spectrometry--a powerful tool to identify novel c-di-GMP
      effector proteins.
AB  - Considerable progress has been made during the last decade towards the
      identification and characterization of enzymes involved in the synthesis
      (diguanylate cyclases) and degradation (phosphodiesterases) of the second
      messenger c-di-GMP. In contrast, little information is available regarding the
      molecular mechanisms and cellular components through which this signaling
      molecule regulates a diverse range of cellular processes. Most of the known
      effector proteins belong to the PilZ family or are degenerated diguanylate
      cyclases or phosphodiesterases that have given up on catalysis and have adopted
      effector function. Thus, to better define the cellular c-di-GMP network in a wide
      range of bacteria experimental methods are required to identify and validate
      novel effectors for which reliable in silico predictions fail. We have recently
      developed a novel Capture Compound Mass Spectrometry (CCMS) based technology as a
      powerful tool to biochemically identify and characterize c-di-GMP binding
      proteins. This technique has previously been reported to be applicable to a wide
      range of organisms(1). Here we give a detailed description of the protocol that
      we utilize to probe such signaling components. As an example, we use Pseudomonas
      aeruginosa, an opportunistic pathogen in which c-di-GMP plays a critical role in
      virulence and biofilm control. CCMS identified 74% (38/51) of the known or
      predicted components of the c-di-GMP network. This study explains the CCMS
      procedure in detail, and establishes it as a powerful and versatile tool to
      identify novel components involved in small molecule signaling. 

PMID- 25867681
TI  - A large-scale proteogenomics study of apicomplexan pathogens-Toxoplasma gondii
      and Neospora caninum.
AB  - Proteomics data can supplement genome annotation efforts, for example being used
      to confirm gene models or correct gene annotation errors. Here, we present a
      large-scale proteogenomics study of two important apicomplexan pathogens:
      Toxoplasma gondii and Neospora caninum. We queried proteomics data against a
      panel of official and alternate gene models generated directly from RNASeq data,
      using several newly generated and some previously published MS datasets for this
      meta-analysis. We identified a total of 201 996 and 39 953 peptide-spectrum
      matches for T. gondii and N. caninum, respectively, at a 1% peptide FDR
      threshold. This equated to the identification of 30 494 distinct peptide
      sequences and 2921 proteins (matches to official gene models) for T. gondii, and
      8911 peptides/1273 proteins for N. caninum following stringent protein-level
      thresholding. We have also identified 289 and 140 loci for T. gondii and N.
      caninum, respectively, which mapped to RNA-Seq-derived gene models used in our
      analysis and apparently absent from the official annotation (release 10 from
      EuPathDB) of these species. We present several examples in our study where the
      RNA-Seq evidence can help in correction of the current gene model and can help in
      discovery of potential new genes. The findings of this study have been integrated
      into the EuPathDB. The data have been deposited to the ProteomeXchange with
      identifiers PXD000297and PXD000298.

PMID- 25867684
TI  - Radical ions of cyclopyrenylene: comparison of spectral properties with
      cycloparaphenylene.
AB  - Hoop-shaped pi-conjugated molecules have attracted much attention. In this study,
      the radical ions of [4]cyclo-2,7-pyrenylene ([4]CPY), a cyclic tetramer of
      pyrene, and [4]cyclo-4,5,9,10-tetrahydro-2,7-pyrenylene ([4]CHPY) were
      investigated using radiation chemical methods, namely, gamma-ray radiolysis and
      pulse radiolysis. The absorption spectra of the radical ions of [4]CPY and
      [4]CHPY showed clear peaks in the near-IR and UV-vis regions similar to those of
      [8]cycloparaphenylene ([8]CPP). Theoretical calculations using time-dependent
      density functional theory provided reasonable assignments of the observed
      absorption bands. It was indicated that the C4-C5 and C9-C10 ethylene bonds of
      [4]CHPY do not contribute to the electronic transitions, resulting in absorption
      spectra similar to those of [8]CPP. On the other hand, it was confirmed that the
      allowed electronic transitions of the radical ions of [4]CPY are different from
      those of the radical ions of [4]CHPY and [8]CPP. 

PMID- 25867683
TI  - Dynamic Contrast-Enhanced Perfusion MRI and Diffusion-Weighted Imaging in Grading
      of Gliomas.
AB  - PURPOSE: Accurate glioma grading is crucial for treatment planning and predicting
      prognosis. We performed a quantitative volumetric analysis to assess the
      diagnostic accuracy of histogram analysis of diffusion-weighted imaging (DWI) and
      dynamic contrast-enhanced (DCE) T1-weighted perfusion imaging in the preoperative
      evaluation of gliomas. METHODS: Sixty-three consecutive patients with
      pathologically confirmed gliomas who underwent baseline DWI and DCE-MRI were
      enrolled. The patients were classified by histopathology according to tumor
      grade: 20 low-grade gliomas (grade II) and 43 high-grade gliomas (grades III and
      IV). Volumes-of-interest were calculated and transferred to DCE perfusion and
      apparent diffusion coefficient (ADC) maps. Histogram analysis was performed to
      determine mean and maximum values for Vp and Ktrans , and mean and minimum values
      for ADC. Comparisons between high-grade and low-grade gliomas, and between grades
      II, III, and IV, were performed. A Mann-Whitney U test at a significance level of
      corrected P <= .01 was used to assess differences. RESULTS: All perfusion
      parameters could differentiate between high-grade and low-grade gliomas (P <
      .001) and between grades II and IV, grades II and III, and grades III and IV.
      Significant differences in minimum ADC were also found (P < .01). Mean ADC only
      differed significantly between high and low grades and grades II and IV (P <
      .01). There were no differences between grades II and III (P = .1) and grades III
      and IV (P = .71). CONCLUSION: When derived from whole-tumor histogram analysis,
      DCE-MRI perfusion parameters performed better than ADC in noninvasively
      discriminating low- from high-grade gliomas.

PMID- 25867685
TI  - Polysubstance use, mental health and high-risk behaviours: Results from the 2012
      Global Drug Survey.
AB  - INTRODUCTION AND AIMS: Polysubstance use is associated with adverse health and
      social outcomes, but few studies have investigated whether these associations
      differ between individuals engaged in different patterns of illicit drug and non
      prescription medication use. DESIGN AND METHODS: Latent class analysis (LCA) was
      used to identify patterns of drug use in the Global Drug Survey, a purposive
      sample collected in late 2012 and surveyed using an online questionnaire
      including past-year drug use, sociodemographics, mental illness, involvement in
      violence and sexual behaviour. The sample analysed (n = 14, 869; median age 27
      years; 68.5% male) included those residing in the UK (n = 5869), Australia (n =
      6313) and the USA (n = 2687). RESULTS: LCA of cannabis, ecstasy, cocaine,
      stimulants, nitrous, ketamine, benzodiazepines and opioid painkiller use
      identified six classes: no polysubstance use (Class 1, 49.1%); cannabis and
      ecstasy (Class 2, 23.6%); all illicit drugs (Class 3, 9.4%); ecstasy and cocaine
      (Class 4, 8.3%); cannabis and medication (Class 5, 5.9%); and all drugs (Class 6,
      3.8%). Participants diagnosed with anxiety were most likely to belong to Class 5
      [odds ratio (OR) 2.66, 95% confidence interval (CI) 2.10-3.38]. Violent behaviour
      was most strongly associated with Class 6 membership (OR 1.9, 95% CI 1.36-2.64).
      Sexual risk-taking also predicted membership of this class (OR 5.79, 95% CI 4.66
      7.18) and Class 4 (OR 4.41, 95% CI 3.57-5.43). DISCUSSION AND CONCLUSIONS: Five
      heterogeneous groups of polysubstance users were identified in this international
      sample covering the UK, Australia and USA. Anxiety disorders were associated with
      medication and cannabis use, while high-risk behaviours predicted use of cocaine
      and ecstasy, or wide-ranging polysubstance use including ketamine and
      medications.

PMID- 25867686
TI  - Polyphenols as possible bioprotectors against cytotoxicity and DNA damage induced
      by ochratoxin A.
AB  - The present study aimed to investigate the protective effects of luteolin (L),
      chlorogenic acid (ChlA) and caffeic acid (CafA) against cyto-genotoxic effects
      caused by OTA. Vero cells and rat lymphocytes were used and viability was
      measured by neutral red uptake, MTT and trypan blue dye exclusion method. L (50
      and 100MUg/mL), ChlA (100 and 200MUg/mL) and CafA (10-50MUg/mL) reduced the
      damage induced by OTA (10MUg/mL) on both cells type shown a good protective
      effect. The comet and micronucleus tests in Balb/c mice were performed. ChlA
      (10mg/kg bw) reduced OTA (0.85mg/kg bw)-induced DNA damage on blood and bone
      marrow cells, CafA (10mg/kg bw) showed protective effect only in blood cells and
      luteolin (2.5mg/kg bw) failed to protect DNA integrity on cells. In conclusion,
      polyphenols tested reduced the toxicity caused by OTA on different target cells
      with good protective effect, being ChlA the compound that showed the best
      effects. 

PMID- 25867687
TI  - Allele frequencies of PON1 Q192R polymorphism in four populations of India.
AB  - The allelic distribution at Paraoxonase 1 (PON1) Q192R polymorphism determines
      differential sensitivity towards certain organophosphate pesticides. The alleles
      Q (Glutamine) and R (Arginine) at amino acid position 192 are responsible for the
      lower and higher activity of the enzyme towards paraoxon respectively, making
      knowledge of this distribution in different populations vital. This study reports
      the genotype and allele frequencies of the Gln192Arg polymorphism of PON1 in four
      populations of India, comprising two caste and two tribal groups hitherto
      unexamined for this polymorphism. The R allele frequencies in Jat, Meo, Santhal
      and Zeliangrong populations were found to be 0.47, 0.45, 0.54 and 0.51
      respectively. The gene diversity analyses show a high genetic differentiation at
      this locus indicative of the role of populations' history and other evolutionary
      forces. A comparison with allele frequencies among 106 populations from different
      continents showed a concordance with their geographic distribution which will
      have repercussions in policies targeting pesticide usage. 

PMID- 25867688
TI  - Human biofluid concentrations of mono(2-ethylhexyl)phthalate extrapolated from
      pharmacokinetics in chimeric mice with humanized liver administered with di(2
      ethylhexyl)phthalate and physiologically based pharmacokinetic modeling.
AB  - Di(2-ethylhexyl)phthalate (DEHP) is a reproductive toxicant in male rodents. The
      aim of the current study was to extrapolate the pharmacokinetics and
      toxicokinetics of mono(2-ethylhexyl)phthalate (MEHP, a primary metabolite of
      DEHP) in humans by using data from oral administration of DEHP to chimeric mice
      transplanted with human hepatocytes. MEHP and its glucuronide were detected in
      plasma from control mice and chimeric mice after single oral doses of 250mg
      DEHP/kg body weight. Biphasic plasma concentration-time curves of MEHP and its
      glucuronide were seen only in control mice. MEHP and its glucuronide were
      extensively excreted in urine within 24h in mice with humanized liver. In
      contrast, fecal excretion levels of MEHP glucuronide were high in control mice
      compared with those with humanized liver. Adjusted animal biomonitoring
      equivalents from chimeric mice studies were scaled to human biomonitoring
      equivalents using known species allometric scaling factors and in vitro metabolic
      clearance data with a simple physiologically based pharmacokinetic (PBPK) model.
      Estimated urine MEHP concentrations in humans were consistent with reported
      concentrations. This research illustrates how chimeric mice transplanted with
      human hepatocytes in combination with a simple PBPK model can assist evaluations
      of pharmacokinetics or toxicokinetics of the primary or secondary metabolites of
      DEHP. 

PMID- 25867689
TI  - Effects of TiO2 nanoparticles on ROS production and growth inhibition using
      freshwater green algae pre-exposed to UV irradiation.
AB  - This study investigated the possibility that titanium dioxide nanoparticles (nano
      TiO2) toxicity in Pseudokirchneriella subcapitata involves reactive oxygen
      species (ROS) production, using the dichlorodihydrofluorescein (DCF) assay. Algae
      were exposed to nano-TiO2 under laboratory fluorescent lamps supplemented with UV
      irradiation for 3h, with or without a UV filter. Results showed that nano-TiO2
      increased ROS production in UV-exposed cells, with or without a UV filter (LOEC
      values were 250 and 10mg/L, respectively). Sublethal effects of nano-TiO2 on UV
      pre-exposed algae were also examined. Toxicity studies indicated that exposure to
      nano-TiO2 agglomerates decreased algal growth following 3h pre-exposure to UV,
      with or without a UV filter (EC50s were 8.7 and 6.3mg/L, respectively). The
      present study suggests that the growth inhibitory effects of nano-TiO2 in algae
      occurred at concentrations lower than those that can elevate DCF fluorescence,
      and that ROS generation is not directly involved with the sublethal effects of
      nano-TiO2 in algae. 

PMID- 25867690
TI  - Ultrastructure of Developing Feline Nonciliated Bronchiolar Epithelial Cells.
AB  - The ultrastructure of the developing bronchiolar cell was studied in six age
      groups: prenatal (60 d post-conception); postnatal (1-, 7-, 14- and 21-day-old);
      and adult. Following intratracheal fixation, the lung tissue was processed for
      scanning and transmission electron microscopy. The lining of terminal bronchioles
      consists of cuboidal to columnar nonciliated bronchiolar cells (NBCs) and
      ciliated with or without microvilli. NBCs were recognized by indented centrally
      located nucleus. The apical surface extended beyond the surface of neighboring
      cells and was covered by minute microvilli, except in prenatal kittens. The NBCs
      of the adult were characterized by abundant mitochondria and glycogen inclusions.
      In prenatal kittens, the cytoplasm was filled with patches of alpha and beta form
      of glycogen. Postnatally, glycogen was reduced in quantity, became scattered
      throughout the cytoplasm and was predominantly of the beta form. Islands of
      cytoplasm, separated from the apical cytoplasm were observed in the lumen of
      adult bronchioles. This suggests an apocrine mode of secretion. The NBCs attain
      maturity by three weeks of age. 

PMID- 25867692
TI  - Ethnic microaggressions, traumatic stress symptoms, and Latino depression: A
      moderated mediational model.
AB  - Although ethnic microaggressions have received increased empirical attention in
      recent years, there remains a paucity of research regarding how these subtle
      covert forms of discrimination contribute to Latino mental health. The present
      study examined the role of traumatic stress symptoms underlying the relationship
      between ethnic microaggressions and depression. Further, ethnic identity and
      general self-efficacy were tested as moderators between the ethnic
      microaggressions and traumatic stress link. Among a sample of 113 Latino adults,
      moderated mediational analyses revealed statistically significant conditional
      indirect effects in which traumatic stress symptoms mediated the relationship
      between ethnic microaggressions and depression while ethnic identity and self
      efficacy functioned as moderators. The major findings suggested that the indirect
      effects were the most robust within low ethnic identity and low self-efficacy.
      The findings are discussed within a stress and coping framework that highlight
      the internal resources and stress responses associated with experiencing ethnic
      microaggressions.

PMID- 25867691
TI  - Preparing adherent cells for X-ray fluorescence imaging by chemical fixation.
AB  - X-ray fluorescence imaging allows us to non-destructively measure the spatial
      distribution and concentration of multiple elements simultaneously over large or
      small sample areas. It has been applied in many areas of science, including
      materials science, geoscience, studying works of cultural heritage, and in
      chemical biology. In the case of chemical biology, for example, visualizing the
      metal distributions within cells allows us to study both naturally-occurring
      metal ions in the cells, as well as exogenously-introduced metals such as drugs
      and nanoparticles. Due to the fully hydrated nature of nearly all biological
      samples, cryo-fixation followed by imaging under cryogenic temperature represents
      the ideal imaging modality currently available. However, under the circumstances
      that such a combination is not easily accessible or practical, aldehyde based
      chemical fixation remains useful and sometimes inevitable. This article describes
      in as much detail as possible in the preparation of adherent mammalian cells by
      chemical fixation for X-ray fluorescent imaging. 

PMID- 25867693
TI  - A randomized controlled trial of cognitive behavioral therapy for insomnia: an
      effective treatment for comorbid insomnia and depression.
AB  - Insomnia and depression are highly comorbid conditions that show a complex,
      bidirectional relationship. This study examined whether cognitive-behavioral
      therapy for insomnia (CBT-I) delivered by a therapist compared with self-help CBT
      I (written materials only) reduces insomnia and depression severity in
      individuals with comorbid insomnia and depression. A total of 41 participants (18
      64 years; 25 females) with comorbid depression and insomnia, treated with
      antidepressants for at least 6 weeks, were randomized to receive 4 sessions of
      either CBT-I or self-help CBT-I over 8 weeks. Insomnia (Insomnia Severity Index
      [ISI]) and depression (Beck Depression Inventory-II [BDI-II]) were assessed at
      baseline, following each session, and at 3-month follow-up. Secondary outcomes
      were sleep quality and duration (actigraphy and diaries), anxiety, fatigue, and
      daytime sleepiness. Compared with self-help CBT-I, BDI-II scores in the CBT-I
      group dropped by 11.93 (95% confidence interval [CI] [6.60, 17.27], p < .001)
      more points, and ISI scores dropped by 6.59 (95% CI [3.04, 10.15], p = .001) more
      points across treatment. At 3-month follow-up, 61.1% of CBT-I participants were
      in clinical remission from their insomnia and depression, compared with 5.6% of
      the self-help group. CONCLUSIONS: CBT-I administered by a therapist produced
      significant reductions in both insomnia and depression severity posttreatment and
      at follow-up, compared with a control condition in which participants received
      only written CBT-I material. Targeting insomnia through CBT-I is efficacious for
      treating comorbid insomnia and depression, and should be considered an important
      adjunct therapy for patients with depression whose symptoms have not remitted
      through antidepressant treatment.

PMID- 25867694
TI  - The lagged effects of racial discrimination on depressive symptomology and
      interactions with racial identity.
AB  - Scholars agree on the negative impacts of racial discrimination on the mental
      health of African Americans (Brondolo et al., 2008). Yet research is needed to
      explore the impacts of everyday discrimination over time, especially compared to
      nonracial daily hassles, in an ecologically valid manner. It is also widely
      accepted that racial identity can moderate the impact of racial hassles (Sellers,
      Copeland-Linder, Martin, & Lewis 2006), but few studies have examined this
      moderating effect over time. The current study addresses gaps in the current
      literature by analyzing the relationship between reported racial and nonracial
      stressors over the course of four days. Participants were 225 college students at
      three institutions who participated in a 20-day daily diary study. Each day,
      participants reported whether they had experienced a stressful event and their
      depressive symptoms. We compared reports of depressive symptoms the day an event
      occurred and two days after for racial and nonracial stressors and examined
      whether racial identity served as a moderator. The results showed that
      individuals experienced similar increases for racial and nonracial stressors when
      events occur and similar decreases in the following two days. Additionally,
      symptom trajectories varied by racial identity. Implications for the
      understanding of racial discrimination's role in the well-being of African
      Americans are discussed.

PMID- 25867695
TI  - Testing a mediation framework for the link between perceived discrimination and
      psychological distress among sexual minority individuals.
AB  - Perceived discrimination is a risk factor for mental health problems among sexual
      minority individuals. An increasing number of research studies have investigated
      the mechanisms through which stigma-related stressors such as perceived
      discrimination are linked with adverse mental health outcomes for sexual minority
      populations. The integrative mediation framework proposed by Hatzenbuehler (2009)
      underscores the importance of identifying mediators in the association between
      stigma-related stressors and mental health outcomes. This study tested 3
      mediators--expectations of rejection, anger rumination, and self-compassion--in
      the perceived discrimination-distress link. Moreover, it examined associations
      among these mediators. A nationwide sample of 265 sexual minorities responded to
      an online survey. Structural equation modeling results supported the mediator
      roles of expectations of rejection, anger rumination, and self-compassion. More
      specifically, perceived discrimination was associated with expectations of
      rejection, which, in turn, was associated with increased anger rumination and
      less self-compassion, resulting in greater psychological distress. The findings
      suggest several avenues for prevention and intervention with sexual minority
      individuals.

PMID- 25867696
TI  - Construction and initial validation of the Gendered Racial Microaggressions Scale
      for Black women.
AB  - The purpose of this study was to develop a measure of gendered racial
      microaggressions (i.e., subtle and everyday verbal, behavioral, and environmental
      expressions of oppression based on the intersection of one's race and gender)
      experienced by Black women by applying an intersectionality framework to Essed's
      (1991) theory of gendered racism and Sue, Capodilupo, et al.'s (2007) model of
      racial microaggressions. The Gendered Racial Microaggressions Scale (GRMS), was
      developed to assess both frequency and stress appraisal of microaggressions, in 2
      separate studies. After the initial pool of GRMS items was developed, we received
      input from a community-based focus group of Black women and an expert panel. In
      Study 1, an exploratory factor analysis using a sample of 259 Black women
      resulted in a multidimensional scale with 4 factors as follows: (a) Assumptions
      of Beauty and Sexual Objectification, (b) Silenced and Marginalized, (c) Strong
      Black Woman Stereotype, and (d) Angry Black Woman Stereotype. In Study 2, results
      of confirmatory factor analyses using an independent sample of 210 Black women
      suggested that the 4-factor model was a good fit of the data for both the
      frequency and stress appraisal scales. Supporting construct validity, the GRMS
      was positively related to the Racial and Ethnic Microaggressions Scale (Nadal,
      2011) and the Schedule of Sexist Events (Klonoff & Landrine, 1995). In addition,
      the GRMS was significantly related to psychological distress, such that greater
      perceived gendered racial microaggressions were related to greater levels of
      reported psychological distress. Implications for future research and practice
      are discussed.

PMID- 25867697
TI  - Forgiving the self and physical and mental health correlates: a meta-analytic
      review.
AB  - Self-forgiveness has been conceptualized as a coping strategy that may improve
      health and well-being. To better understand the functions of self-forgiveness,
      this meta-analysis examines the correlates of self-forgiveness associated with
      physical and mental health. For physical health, across 18 samples and 5,653
      participants, the correlation was .32. For psychological well-being, across 65
      samples and 17,939 participants, the correlation was .45. To augment this primary
      focus on physical and mental health correlates, we estimated the relationships
      between self-forgiveness and specific mental health constructs and relationship
      outcomes. Implications for future basic and applied research on self-forgiveness
      are discussed.

PMID- 25867698
TI  - Erratum.

PMID- 25867699
TI  - Binding and ratiometric dual ion recognition of Zn(2+) and Cu(2+) by 1,3,5-tris
      amidoquinoline conjugate of calix[6]arene by spectroscopy and its supramolecular
      features by microscopy.
AB  - Lower rim amide linked 8-amino quinoline and 8-amino naphthalene moiety 1,3,5
      triderivatives of calix[6]arene L1 and L2 have been synthesized and
      characterized. While the L1 acts as a receptor molecule, the L2 acts as a control
      molecule. The complexation between L1 and Cu(2+) or Zn(2+) was delineated by the
      absorption and electrospray ionization (ESI) MS spectra. The binding ability of
      these molecules toward biologically important metal ions was studied by
      fluorescence and absorption spectroscopy. The derivative L1 detects Zn(2+) by
      bringing ratiometric change in the fluorescence signals at 390 and 490 nm, but in
      the case of Cu(2+), it is only the fluorescence quenching of 390 nm band that is
      observed, while no new band is observed at 390 nm. The stoichiometry of both the
      complexes is 1:1 and was confirmed in both the cases by measuring the ESI mass
      spectra. The isotopic peak pattern observed in the ESI MS confirmed the presence
      of Zn(2+) or Cu(2+) present in the corresponding complex formed with L1. Among
      these two ions, the Cu(2+) exhibits higher sensitivity. The density-functional
      theory (DFT) studies revealed the conformational changes in the arms and also
      revealed the coordination features in the case of the metal complexes. The arm
      conformational changes upon Zn(2+) binding were supported by nuclear Overhauser
      effect spectrometry (NOESY) studies. The stronger binding of Cu(2+) over that of
      Zn(2+) observed from the absorption study was further supported by the
      complexational energies computed from the computational data. While the L1
      exhibited spherical particles, upon complexation with Cu(2+), it exhibits chain
      like morphological features in scanning electron microscopy (SEM) but only small
      aggregates in the case of Zn(2+). Thus, even the microscopy data can
      differentiate the complex formed between L1 and Cu(2+) from that formed with
      Zn(2+). 

PMID- 25867700
TI  - Evaluation of instrumentation systems in reducing E. faecalis from root canals:
      TF adaptive and ProTaper next versus single file systems.
AB  - PURPOSE: To compare the effect of the TF Adaptive, ProTaper Next, OneShape,
      WaveOne, Reciproc, (SAF) on the reduction of E. faecalis in experimentally
      infected root canals. MATERIALS AND METHODS: 70 human mandibular incisor teeth
      with straight roots and single root canals were selected for this experiment and
      the root canals of the selected teeth were infected with E. faecalis. After
      contamination, all the root canals were randomly divided into 7 groups: control,
      ProTaper Next, TF Adaptive, SAF, WaveOne, Reciproc, and OneShape. After the
      irrigation procedures, samples were taken from root canals with paper points and
      incubated in blood agar plates. The colonies grown on the blood agar were counted
      and interpreted as colony forming units per milliliter. RESULTS: Analysis of
      results showed that all instrumentation systems were more effective in reducing
      the number of bacteria than the control (P<.001). The ProTaper Next, TF Adaptive,
      WaveOne, Reciproc, and OneShape systems were significantly more effective than
      the SAF system in reducing E. faecalis within the root canals (P<.001).
      CONCLUSIONS: All instrumentation systems used in this study provided a
      significant reduction in bacterial populations.

PMID- 25867701
TI  - A digital assessment and documentation tool evaluated for daily podiatric wound
      practice.
AB  - INTRODUCTION: Foot ulcers are a common complication of diabetes. Regular
      screening of patients with ulcers enables better treatment and reduces the number
      of amputations. The lack of wound specialists, especially in nonurban areas,
      drove the development of an IT-based system for analyzing wounds, the Wound
      Healing Analyzing Tool (WHAT). Digital images are scored and documented using
      software that runs on a laptop computer. The aim of this study was to evaluate
      WHAT's use in daily podiatry practice. METHODS: Eighteen ambulant patients
      presenting with diabetic foot ulcers at the participating podiatric clinic were
      recruited to the study. Digital ulcer images were obtained. To measure size and
      assess wound bed condition, the evaluated software recognizes the square mark,
      which is printed on a sticker and placed next to the ulcer. A trained, blinded
      physician assessed the same digital images and results were compared. RESULTS:
      Fifteen of the 18 results obtained with the digital tool for ulcer area and wound
      bed condition were in line with the visual assessment conducted by the blinded
      physician. Eighty-seven percent of the images were correctly scored, with the
      main problem being a missing or partially visible square mark in the photograph
      (n = 3/18). CONCLUSION: The results indicate that WHAT showed sufficient accuracy
      to be considered for use in clinical settings for determination of wound area and
      wound bed characteristics. The tool also seems to be an attractive option for
      digital consulting.

PMID- 25867702
TI  - Wound fluid management in wound care: the role of a hydroconductive dressing.
AB  - A case series was conducted to evaluate the clinical experience with a new
      hydroconductive wound dressing, that appears to help facilitate the removal of
      necrotic tissue and other deterrents to wound healing while preserving healthy
      granulation tissue in a wound. Eight patients were treated with the dressing
      which has a proprietary technology that draws fluid away from the wound. The
      dressing was used on a variety of wound types and all wounds went on to heal by
      secondary intention. There were no adverse effects noted by any patient in the
      case series. Larger patient studies are needed to corroborate the positive
      clinical results that were observed in this series of patients.    . 

PMID- 25867703
TI  - [Not Available].
AB  - OBJECTIVE: Bulb suction drains have long been used in various surgical
      procedures. The purpose of this study was to evaluate 4 commonly used bulb
      suction devices in vitro to explore the nonlinear changes in draining ability and
      efficiency along with the conformation changes of the device throughout the
      draining processes. METHODS: Under a designed simulated scenario using pure water
      as the desired draining substance, the relative function of the J-VAC 100 cc
      (JV100) (Ethicon, Inc, Somerville, USA); the EVACUATOR 125cc (EP125) (Pacific
      Hospital Supply, Taiwan); the Bulb Reservoir 150 cc (BH150) (Hosmed, Inc, Miami,
      FL); and the HemoVac 400 cc (HV400) (Zimmer, Inc, Warsaw, IN) drains were
      compared. The maximum collection capacities and the dead space at maximum
      compression of each bulb drain were recorded and compared. The collected fluid
      weight was recorded along with time, and collection speeds were calculated and
      compared. RESULTS: The maximum collected weight of the 4 drains were 110.07 +/-
      0.54 g (JV100), 122.7 +/- 06.51 g (EP125), 140.8 +/- 03.78 g (BH150), and 335.07
      +/- 04.24 g (HV400). The dead spaces under maximum compression were 15.63 +/-
      01.32 ml, 19.80 +/- 03.37 ml, 34.23 +/- 06.77 ml, and 82.83 +/- 05.51 ml,
      respectively. The collecting speed-volume curves were generated from the authors'
      tested devices. Although slightly different individually, typical
      characteristics, such as tendency to reach maximum collection speed at the very
      beginning of the collection phase; rapid decline to about 65% of peak collection
      speed when approximately 30% of the total collection volume had been achieved;
      and inefficient collection speed in the later collection phase were noted.
      CONCLUSIONS: Among all the bulb drains tested in this study, all of them
      performed well in vitro. Although using bulb drains continues to be an effective
      and economic draining method after operation, clinicians should be aware of the
      nonlinear features of suction efficiency during the drainage process to avoid
      unexpected function deterioration.  .

PMID- 25867704
TI  - [Not Available].
AB  - Objective. To assess sleep quality in a population of patients with diabetic
      foot ulcers. METHODS: This was an exploratory, descriptive, cross-sectional
      study. The Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality
      in 60 patients with diabetes mellitus and foot ulcers. RESULTS: Seventeen (28.3%)
      patients had a global PSQI score less than 5, indicating that they were good
      sleepers, while 43 (71.7%) patients were considered poor sleepers. The patients
      reported going to bed between 9:00 pm and 11:00 pm (n = 40, 66.70%), taking from
      16 minutes to 30 minutes to fall asleep (n = 25, 41.70%), and waking up after 4
      hours to 5 hours of sleep (n = 40, 66.70%). CONCLUSION: Patients with diabetic
      foot ulcers have poor sleep quality.    .

PMID- 25867705
TI  - Low-priced, time-saving, reliable and stable LR-115 counting system.
AB  - Nuclear alpha particles leave etches (tracks) when they hit the surface of a LR
      115 detector. The density of these tracks is used to measure radon concentration.
      Counting these tracks by human sense is tedious and time-consuming procedure and
      may introduce counting error, whereas most available automatic and semiautomatic
      counting systems are expensive or complex. An uncomplicated, robust, reliable and
      stable counting system using freely available on the Internet software as
      DigimizerTM and PhotoScape was developed and proposed. The effectiveness of the
      proposed procedure was evaluated by comparing the amount of tracks counted by
      software with the amount of tracks counted manually for 223 detectors. The
      percentage error for each analysed detector was obtained as a difference between
      automatic and manual counts divided by manual count. For more than 97% of
      detectors, the percentage errors oscillated between -3% and 3%. 

PMID- 25867706
TI  - Truths and misinformation: a qualitative exploration of myotonic dystrophy.
AB  - BACKGROUND: Myotonic dystrophy (DM1) is an autosomal dominant, progressive, and
      multisystem condition that impacts affected individuals physically, socially, and
      emotionally. Understanding individuals' perceptions of their disease is critical
      to ensuring appropriate information, education, and counseling. METHODS: We
      conducted a content analysis of findings from a larger study that used a novel,
      qualitative research approach called photovoice to explore nine patients'
      experiences of living with DM1. Participants took pictures that illustrated
      barriers or facilitators to living with DM1; their photographs then formed the
      basis of semistructured interviews. Transcripts were analyzed and, among themes,
      we identified one titled "DM1 truths and misinformation" that described
      participants' disease knowledge. Analysis revealed four categories within this
      broader theme: "the physical and emotional cost of DM1," "managing my DM1,"
      "genetics and me" and "patients as advocates and educators." RESULTS: Findings
      showed that DM1 participants had good core knowledge with respect to their
      disease and its implications. However, each participant held as fact fragments of
      misinformation that shaped decision-making and pointed to a clear need for
      strategies to mitigate variable interpretation of health information.
      CONCLUSIONS: We conclude that there is a need for increased education and
      awareness about symptoms, genetic information and treatment strategies for
      patients, their family members, and health care providers.

PMID- 25867707
TI  - Thyroid Hormone-Otx2 Signaling Is Required for Embryonic Ventral Midbrain Neural
      Stem Cells Differentiated into Dopamine Neurons.
AB  - Midbrain dopamine (DA) neurons are essential for maintaining multiple brain
      functions. These neurons have also been implicated in relation with diverse
      neurological disorders. However, how these neurons are developed from neuronal
      stem cells (NSCs) remains largely unknown. In this study, we provide both in vivo
      and in vitro evidence that the thyroid hormone, an important physiological factor
      for brain development, promotes DA neuron differentiation from embryonic ventral
      midbrain (VM) NSCs. We find that thyroid hormone deficiency during development
      reduces the midbrain DA neuron number, downregulates the expression of tyrosine
      hydroxylase (TH) and the dopamine transporter (DAT), and impairs the DA neuron
      dependent motor behavior. In addition, thyroid hormone treatment during VM NSC
      differentiation in vitro increases the production of DA neurons and upregulates
      the expression of TH and DAT. We also found that the thyroid hormone enhances the
      expression of Otx2, an important determinant of DA neurogenesis, during DA neuron
      differentiation. Our in vitro gene silencing experiments indicate that Otx2 is
      required for thyroid hormone-dependent DA neuron differentiation from embryonic
      VM NSCs. Finally, we revealed both in vivo and in vitro that the thyroid hormone
      receptor alpha 1 is expressed in embryonic VM NSCs. Furthermore, it participates
      in the effects of thyroid hormone-induced Otx2 upregulation and DA neuron
      differentiation. These data demonstrate the role and molecular mechanisms of how
      the thyroid hormone regulates DA neuron differentiation from embryonic VM NSCs,
      particularly providing new mechanisms and a potential strategy for generating
      dopamine neurons from NSCs. 

PMID- 25867708
TI  - High-throughput screening for chemical modulators of post-transcriptionally
      regulated genes.
AB  - Both transcriptional and post-transcriptional regulation have a profound impact
      on genes expression. However, commonly adopted cell-based screening assays focus
      on transcriptional regulation, being essentially aimed at the identification of
      promoter-targeting molecules. As a result, post-transcriptional mechanisms are
      largely uncovered by gene expression targeted drug development. Here we describe
      a cell-based assay aimed at investigating the role of the 3' untranslated region
      (3' UTR) in the modulation of the fate of its mRNA, and at identifying compounds
      able to modify it. The assay is based on the use of a luciferase reporter
      construct containing the 3' UTR of a gene of interest stably integrated into a
      disease-relevant cell line. The protocol is divided into two parts, with the
      initial focus on the primary screening aimed at the identification of molecules
      affecting luciferase activity after 24 hr of treatment. The second part of the
      protocol describes the counter-screening necessary to discriminate compounds
      modulating luciferase activity specifically through the 3' UTR. In addition to
      the detailed protocol and representative results, we provide important
      considerations about the assay development and the validation of the hit(s) on
      the endogenous target. The described cell-based reporter gene assay will allow
      scientists to identify molecules modulating protein levels via post
      transcriptional mechanisms dependent on a 3' UTR. 

PMID- 25867710
TI  - Persistence of Long-Term Memory in Vitrified and Revived Caenorhabditis elegans.
AB  - Can memory be retained after cryopreservation? Our research has attempted to
      answer this long-standing question by using the nematode worm Caenorhabditis
      elegans, a well-known model organism for biological research that has generated
      revolutionary findings but has not been tested for memory retention after
      cryopreservation. Our study's goal was to test C. elegans' memory recall after
      vitrification and reviving. Using a method of sensory imprinting in the young C.
      elegans, we establish that learning acquired through olfactory cues shapes the
      animal's behavior and the learning is retained at the adult stage after
      vitrification. Our research method included olfactory imprinting with the
      chemical benzaldehyde (C6H5CHO) for phase-sense olfactory imprinting at the L1
      stage, the fast-cooling SafeSpeed method for vitrification at the L2 stage,
      reviving, and a chemotaxis assay for testing memory retention of learning at the
      adult stage. Our results in testing memory retention after cryopreservation show
      that the mechanisms that regulate the odorant imprinting (a form of long-term
      memory) in C. elegans have not been modified by the process of vitrification or
      by slow freezing. 

PMID- 25867709
TI  - Current Ideas about Prebiological Compartmentalization.
AB  - Contemporary biological cells are highly sophisticated dynamic compartment
      systems which separate an internal volume from the external medium through a
      boundary, which controls, in complex ways, the exchange of matter and energy
      between the cell's interior and the environment. Since such compartmentalization
      is a fundamental principle of all forms of life, scenarios have been elaborated
      about the emergence of prebiological compartments on early Earth, in particular
      about their likely structural characteristics and dynamic features. Chemical
      systems that consist of potentially prebiological compartments and chemical
      reaction networks have been designed to model pre-cellular systems. These systems
      are often referred to as "protocells". Past and current protocell model systems
      are presented and compared. Since the prebiotic formation of cell-like
      compartments is directly linked to the prebiotic availability of compartment
      building blocks, a few aspects on the likely chemical inventory on the early
      Earth are also summarized. 

PMID- 25867711
TI  - Validation of nanobody and antibody based in vivo tumor xenograft NIRF-imaging
      experiments in mice using ex vivo flow cytometry and microscopy.
AB  - This protocol outlines the steps required to perform ex vivo validation of in
      vivo near-infrared fluorescence (NIRF) xenograft imaging experiments in mice
      using fluorophore labelled nanobodies and conventional antibodies. First we
      describe how to generate subcutaneous tumors in mice, using antigen-negative cell
      lines as negative controls and antigen-positive cells as positive controls in the
      same mice for intraindividual comparison. We outline how to administer
      intravenously near-infrared fluorophore labelled (AlexaFluor680) antigen-specific
      nanobodies and conventional antibodies. In vivo imaging was performed with a
      small-animal NIRF-Imaging system. After the in vivo imaging experiments the mice
      were sacrificed. We then describe how to prepare the tumors for parallel ex vivo
      analyses by flow cytometry and fluorescence microscopy to validate in vivo
      imaging results. The use of the near-infrared fluorophore labelled nanobodies
      allows for non-invasive same day imaging in vivo. Our protocols describe the ex
      vivo quantification of the specific labeling efficiency of tumor cells by flow
      cytometry and analysis of the distribution of the antibody constructs within the
      tumors by fluorescence microscopy. Using near-infrared fluorophore labelled
      probes allows for non-invasive, economical in vivo imaging with the unique
      ability to exploit the same probe without further secondary labelling for ex vivo
      validation experiments using flow cytometry and fluorescence microscopy. 

PMID- 25867713
TI  - Risk Reduction Modeling of High Pathogenicity Avian Influenza Virus Titers in
      Nonpasteurized Liquid Egg Obtained from Infected but Undetected Chicken Flocks.
AB  - Control of highly pathogenic avian influenza (HPAI) outbreaks in poultry has
      traditionally involved the establishment of disease containment zones, where
      poultry products are only permitted to move from within a zone under permit.
      Nonpasteurized liquid egg (NPLE) is one such commodity for which movements may be
      permitted, considering inactivation of HPAI virus via pasteurization. Active
      surveillance testing at the flock level, using targeted matrix gene real-time
      reversed transcriptase-polymerase chain reaction testing (RRT-PCR) has been
      incorporated into HPAI emergency response plans as the primary on-farm diagnostic
      test procedure to detect HPAI in poultry and is considered to be a key risk
      mitigation measure. To inform decisions regarding the potential movement of NPLE
      to a pasteurization facility, average HPAI virus concentrations in NPLE produced
      from a HPAI virus infected, but undetected, commercial table-egg-layer flock were
      estimated for three HPAI virus strains using quantitative simulation models.
      Pasteurization under newly proposed international design standards (5 log10
      reduction) is predicted to inactivate HPAI virus in NPLE to a very low
      concentration of less than 1 embryo infectious dose (EID)50 /mL, considering the
      predicted virus titers in NPLE from a table-egg flock under active surveillance.
      Dilution of HPAI virus from contaminated eggs in eggs from the same flock, and in
      a 40,000 lb tanker-truck load of NPLE containing eggs from disease-free flocks
      was also considered. Risk assessment can be useful in the evaluation of commodity
      specific risk mitigation measures to facilitate safe trade in animal products
      from countries experiencing outbreaks of highly transmissible animal diseases. 

PMID- 25867712
TI  - Telmisartan attenuates peritoneal fibrosis via peroxisome proliferator-activated
      receptor-gamma activation in rats.
AB  - Peritoneal dialysis (PD) is an effective treatment for patients with end-stage
      renal diseases, but long-term continuous PD causes peritoneal fibrosis (PF). This
      study aims to evaluate the anti-fibrotic effect of telmisartan on a rat model of
      PF and to investigate the underlying mechanisms. Five-sixths kidney nephrectomy
      and PD were used to establish the PF rat model. Glucose (2.5%) was used to
      establish an in vitro model in rat peritoneal mesothelial cells (PMC).
      Haematoxylin-eosin staining was used to examine the structural alterations.
      Masson's trichrome staining was used to observe the tissue fibrosis in peritoneal
      membrane of rats. Real-time polymerase chain reaction was used to measure
      messenger RNA expressions of profibrotic factors. Western blotting was used to
      determine protein expressions of profibrotic factors, peroxisome proliferator
      activated receptor-gamma, and mitogen-activated protein kinases (MAPK). Results
      demonstrated that administration of telmisartan dose-dependently attenuated the
      thickening of the peritoneal membrane and the fibrosis induced by long-term PD
      fluid exposure in rats. In addition, telmisartan treatment inhibited the
      upregulation of profibrotic factors induced by PD in the peritoneum of rats and
      by high-concentration glucose in PMC. Telmisartan was also effective in
      inhibiting PD and high-concentration, glucose-induced phosphorylation of MAPK in
      the peritoneum and PMC. Furthermore, peroxisome proliferator-activated receptor
      gamma (PPARgamma) inhibitor GW9662 blocked these protective effects of
      telmisartan in PMC. The results suggest that telmisartan is effective in
      attenuating PD-induced PF, and this effect may be associated with the inhibition
      of profibrotic factor expression and MAPK phosphorylation via PPARgamma
      activation. 

PMID- 25867714
TI  - Two Unusual Polycyclic Polyprenylated Acylphloroglucinols, Including a Pair of
      Enantiomers from Garcinia multiflora.
AB  - Two polycyclic polyprenylated acylphloroglucinols, garcimulins A and B ((+/-)-1
      and 2), including a pair of enantiomers with the unique caged
      tetracyclo[5.4.1.1(1,5).0(9,13)]tridecane skeleton were isolated from Garcinia
      multiflora. Their structures and absolute configurations were determined by
      extensive analysis of spectroscopic data and electronic circular dichroism (ECD)
      calculations. Compounds 1 and 2 exhibited cytotoxic activities against five human
      cancer cell lines in vitro (IC50 3.42-13.23 MUM). The acidification of lysosomes
      in HeLa cell was obviously affected by compound 2. 

PMID- 25867715
TI  - Clinical implementation of NIPT - technical and biological challenges.
AB  - Non-invasive prenatal testing (NIPT) for fetal aneuploidy detection is
      increasingly being offered in the clinical setting. Whereas the majority of tests
      only report fetal trisomies 21, 18 and 13, genome-wide analyses have the
      potential to detect other fetal, as well as maternal, aneuploidies. In this
      review, we discuss the technical and clinical advantages and challenges
      associated with genome-wide cell-free fetal DNA profiling.

PMID- 25867716
TI  - Experimental demyelination and remyelination of murine spinal cord by focal
      injection of lysolecithin.
AB  - Multiple sclerosis is an inflammatory demyelinating disease of the central
      nervous system characterized by plaque formation containing lost
      oligodendrocytes, myelin, axons, and neurons. Remyelination is an endogenous
      repair mechanism whereby new myelin is produced subsequent to proliferation,
      recruitment, and differentiation of oligodendrocyte precursor cells into myelin
      forming oligodendrocytes, and is necessary to protect axons from further damage.
      Currently, all therapeutics for the treatment of multiple sclerosis target the
      aberrant immune component of the disease, which reduce inflammatory relapses but
      do not prevent progression to irreversible neurological decline. It is therefore
      imperative that remyelination-promoting strategies be developed which may delay
      disease progression and perhaps reverse neurological symptoms. Several animal
      models of demyelination exist, including experimental autoimmune
      encephalomyelitis and curprizone; however, there are limitations in their use for
      studying remyelination. A more robust approach is the focal injection of toxins
      into the central nervous system, including the detergent lysolecithin into the
      spinal cord white matter of rodents. In this protocol, we demonstrate that the
      surgical procedure involved in injecting lysolecithin into the ventral white
      matter of mice is fast, cost-effective, and requires no additional materials than
      those commercially available. This procedure is important not only for studying
      the normal events involved in the remyelination process, but also as a pre
      clinical tool for screening candidate remyelination-promoting therapeutics. 

PMID- 25867718
TI  - Sequential or concomitant therapy for eradication of Helicobacter pylori
      infection: A systematic review and meta-analysis.
AB  - BACKGROUND AND AIM: Eradication of Helicobacter pylori (H. pylori) infection with
      triple therapy (TT) has declined in many countries prompting the search for
      alternative regimens. Sequential therapy (ST) and concomitant therapy (CT) have
      been suggested as first-line regimens in areas of high clarithromycin resistance.
      We performed a meta-analysis to compare the eradication rates of CT with ST for
      H. pylori. METHODS: A comprehensive literature search for studies comparing the
      efficacy of CT with ST was performed. Dichotomous data were pooled to obtain the
      odds ratio (OR) of the eradication rate with 95% confidence intervals (CIs). The
      eradication rates were considered both on an intention-to-treat (ITT) and on a
      per-protocol (PP) bases. RESULTS: A total of 7 studies provided data on 2412
      adult patients. Pooled estimates of the studies revealed no significant
      differences between CT and ST. The pooled OR was 1.116 (95% CI: 0.795-1.567, P =
      0.526) for ITT analysis and 1.153 (95% CI: 0.793-1.677, P = 0.455) for PP
      analysis. There was no difference in the rate of adverse events (OR: 1.229, 95%
      CI: 0.971-1.556, P = 0.086) and compliance (OR: 0.945, 95% CI: 0.722-1.237, P =
      0.681) between the two regimens. Subgroup analysis was performed to compare CT of
      10 days and 5 days with ST of 10 days. The pooled OR was 1.518 for CT of 10 days
      and 0.636 for CT of 5 days. CONCLUSIONS: CT regimens did not achieve higher
      eradication rates compared with the ST regimen. The adverse events and adherence
      to medications were not different between the two regimens.

PMID- 25867717
TI  - Prediction of breast cancer survival using clinical and genetic markers by tumor
      subtypes.
AB  - PURPOSE: To identify the genetic variants associated with breast cancer survival,
      a genome-wide association study (GWAS) was conducted of Korean breast cancer
      patients. METHODS: From the Seoul Breast Cancer Study (SEBCS), 3,226 patients
      with breast cancer (1,732 in the discovery and 1,494 in the replication set) were
      included in a two-stage GWAS on disease-free survival (DFS) by tumor subtypes
      based on hormone receptor (HR) and human epidermal growth factor receptor 2
      (HER2). The associations of the re-classified combined prognostic markers through
      recursive partitioning analysis (RPA) of DFS for breast cancer were assessed with
      the Cox proportional hazard model. The prognostic predictive values of the
      clinical and genetic models were evaluated by Harrell's C. RESULTS: In the two
      stage GWAS stratified by tumor subtypes, rs166870 and rs10825036 were
      consistently associated with DFS in the HR+ HER2- and HR- HER2- breast cancer
      subtypes, respectively (Prs166870 = 2.88 * 10(-7) and Prs10825036 = 3.54 * 10(-7)
      in the combined set). When patients were classified by the RPA in each subtype,
      genetic factors contributed significantly to differentiating the high risk group
      associated with DFS inbreast cancer, specifically the HR+ HER2- (P discovery=1.18
      * 10(-8) and P replication = 2.08 * 10(-5)) and HR- HRE2- subtypes (P discovery =
      2.35 * 10(-4) and P replication = 2.60 * 10(-2)). The inclusion of the SNPs
      tended to improve the performance of the prognostic models consisting of age, TNM
      stage and tumor subtypes based on ER, PR, and HER2 status. CONCLUSION: Combined
      prognostic markers that include clinical and genetic factors by tumor subtypes
      could improve the prediction of survival in breast cancer.

PMID- 25867721
TI  - Elevated blood mercury levels in idiopathic axonal neuropathy.

PMID- 25867722
TI  - Stroke care within the golden hour.

PMID- 25867723
TI  - Stroke care within the golden hour.

PMID- 25867724
TI  - Stroke care within the golden hour--in reply.

PMID- 25867725
TI  - Validation of the association between neurologic improvement with decline in
      blood pressure and recanalization in stroke.

PMID- 25867726
TI  - Validation of the association between neurologic improvement with decline in
      blood pressure and recanalization in stroke--in reply.

PMID- 25867727
TI  - Apolipoprotein E and neurocognitive function.

PMID- 25867728
TI  - Restless genital syndrome.

PMID- 25867729
TI  - Apolipoprotein E and neurocognitive function--in reply.

PMID- 25867730
TI  - Restless genital syndrome--in reply.

PMID- 25867732
TI  - Typographical errors and incomplete affiliation.

PMID- 25867731
TI  - Vaccination, infection, and the risk for multiple sclerosis.

PMID- 25867733
TI  - Error in reply letter.

PMID- 25867734
TI  - Error in byline.

PMID- 25867735
TI  - Mutation goes global.

PMID- 25867736
TI  - Functional Characterization of AAV-Expressed Recombinant Anti-VEGF Single-Chain
      Variable Fragments In Vitro.
AB  - PURPOSE: Most retinal neovascular disorders are caused by upregulation of
      vascular endothelial growth factor (VEGF) expression. These disorders are treated
      with repeated injections of anti-VEGF molecules, which may have severe side
      effects. The expression of anti-VEGF molecules by the retina itself in a
      controlled manner following adeno-associated viral (AAV) gene transfer could be a
      replacement of this therapy. METHODS: The open reading frames (orf) of the light
      and the heavy chain of ranibizumab were cloned into an expression plasmid
      separated by an internal ribosomal entry site (IRES). The construct was mutated
      to generate ranibizumab single-chain variable fragments (scFv). Expression was
      verified by western blotting and the concentrations were measured with a custom
      made ranibizumab ELISA. Biological activity, VEGF-binding properties, and the
      doxycycline-dependent induction of anti-VEGF expression were tested. An AAV2/5
      vector was generated containing the optimal variant Ra02. RESULTS: Ra01-Ra05
      molecules were detected in the cell culture medium. While the VEGF-binding
      affinity was significantly lower for Ra01 and Ra02 compared to Lucentis((r)), the
      inhibition of cell migration was comparable and the maximum inhibition of Ra01
      and Ra02 was reached at lower doses. The expression of Ra01 and Ra02 was shown to
      be regulable with the TetOn-system((r)) as plasmid (Ra01, Ra02) and AAV vector
      construct (Ra02). CONCLUSION: Ra01 and Ra02 can be produced in eukaryotic cells
      after AAV-mediated gene transfer in a regulable manner in vitro and display
      comparable biological activity as Lucentis. These results are the basis for in
      vivo studies in human VEGF-overexpressing mice, a model for human neovascular
      disorders.

PMID- 25867737
TI  - Synthesis and structure-activity relationship of novel 1,4
      diazabicyclo[2.2.2]octane derivatives as potent antimicrobial agents.
AB  - A series of new quaternary 1,4-diazabicyclo[2.2.2]octane derivatives was
      synthesized and evaluated for activity against several strains of both Gram
      positive and Gram negative bacteria and one strain of fungus under different
      inoculum size. Minimum inhibitory concentration (MIC) and minimum bactericidal
      concentration (MBC) against six species of microorganisms were tested. Results
      show a clear structure-activity relationship between alkyl chain length of
      substitutions of 1,4-diazabicyclo[2.2.2]octane tertiary amine sites and
      antimicrobial activity. In the case of compounds 4a-4k, MIC was found to decrease
      with the increase of the alkyl chain length from ethyl to dodecyl and then to
      increase at higher chain length (n > 14). The MIC values were found to be low for
      the compounds 4f and 4g with alkyl chains ranging from 10 to 12 carbons in length
      (1.6 MUg/ml) and were comparable to the reference drug Ciprofloxacin. Also, time
      kill assay was performed to examine the bactericidal kinetics. Results indicated
      that 4f and 4g had rapid killing effects against Staphylococcus aureus, and
      eliminated 100% of the initial inoculum of bacteria in 2.5 h at the concentration
      of 10 MUg/ml. In addition, compound 4g eliminate more than 99.9% of the initial
      inoculum of Ps. aeruginosa after 2.5 h of interaction but the activity of
      compound 4f against this species seems to be weak. Thus, 4g had strong
      bactericidal activity and could rapidly kill Gram positive S. aureus, as well as
      Gram negative Ps. aeruginosa at low and high inoculum size. 

PMID- 25867738
TI  - Derivation of highly purified cardiomyocytes from human induced pluripotent stem
      cells using small molecule-modulated differentiation and subsequent glucose
      starvation.
AB  - Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have
      become an important cell source to address the lack of primary cardiomyocytes
      available for basic research and translational applications. To differentiate
      hiPSCs into cardiomyocytes, various protocols including embryoid body (EB)-based
      differentiation and growth factor induction have been developed. However, these
      protocols are inefficient and highly variable in their ability to generate
      purified cardiomyocytes. Recently, a small molecule-based protocol utilizing
      modulation of Wnt/beta-Catenin signaling was shown to promote cardiac
      differentiation with high efficiency. With this protocol, greater than 50%-60% of
      differentiated cells were cardiac troponin-positive cardiomyocytes were
      consistently observed. To further increase cardiomyocyte purity, the
      differentiated cells were subjected to glucose starvation to specifically
      eliminate non-cardiomyocytes based on the metabolic differences between
      cardiomyocytes and non-cardiomyocytes. Using this selection strategy, we
      consistently obtained a greater than 30% increase in the ratio of cardiomyocytes
      to non-cardiomyocytes in a population of differentiated cells. These highly
      purified cardiomyocytes should enhance the reliability of results from human iPSC
      based in vitro disease modeling studies and drug screening assays. 

PMID- 25867739
TI  - Tactile signals transmitted by the vibrissa during active whisking behavior.
AB  - The rodent vibrissal-trigeminal system is one of the most widely used models for
      the study of somatosensation and tactile perception, but to date the field has
      been unable to quantify the complete set of mechanical input signals generated
      during natural whisking behavior. In this report we show that during whisking
      behavior of awake rats (Rattus norvegicus), the whisker will often bend out of
      its plane of rotation, generating sizeable mechanical (tactile) signals out of
      the plane. We then develop a model of whisker bending that allows us to compute
      the three-dimensional tactile signals at the vibrissal base during active
      whisking behavior. Considerable information can be lost if whisking motions are
      considered only in two dimensions, and we offer some suggestions for
      experimentalists concerned with monitoring the direction of bending. These data
      represent the first quantification of the physical signals transmitted to the
      mechanoreceptors in the follicle during active whisking behavior. 

PMID- 25867740
TI  - Motion dependence of smooth pursuit eye movements in the marmoset.
AB  - Smooth pursuit eye movements stabilize slow-moving objects on the retina by
      matching eye velocity with target velocity. Two critical components are required
      to generate smooth pursuit: first, because it is a voluntary eye movement, the
      subject must select a target to pursue to engage the tracking system; and second,
      generating smooth pursuit requires a moving stimulus. We examined whether this
      behavior also exists in the common marmoset, a New World primate that is
      increasingly attracting attention as a genetic model for mental disease and
      systems neuroscience. We measured smooth pursuit in two marmosets, previously
      trained to perform fixation tasks, using the standard Rashbass step-ramp pursuit
      paradigm. We first measured the aspects of visual motion that drive pursuit eye
      movements. Smooth eye movements were in the same direction as target motion,
      indicating that pursuit was driven by target movement rather than by
      displacement. Both the open-loop acceleration and closed-loop eye velocity
      exhibited a linear relationship with target velocity for slow-moving targets, but
      this relationship declined for higher speeds. We next examined whether marmoset
      pursuit eye movements depend on an active engagement of the pursuit system by
      measuring smooth eye movements evoked by small perturbations of motion from
      fixation or during pursuit. Pursuit eye movements were much larger during pursuit
      than from fixation, indicating that pursuit is actively gated. Several practical
      advantages of the marmoset brain, including the accessibility of the middle
      temporal (MT) area and frontal eye fields at the cortical surface, merit its
      utilization for studying pursuit movements. 

PMID- 25867741
TI  - Voltage gating by molecular subunits of Na+ and K+ ion channels: higher
      dimensional cubic kinetics, rate constants, and temperature.
AB  - The structural similarity between the primary molecules of voltage-gated Na and K
      channels (alpha subunits) and activation gating in the Hodgkin-Huxley model is
      brought into full agreement by increasing the model's sodium kinetics to fourth
      order (m(3) -> m(4)). Both structures then virtually imply activation gating by
      four independent subprocesses acting in parallel. The kinetics coalesce in four
      dimensional (4D) cubic diagrams (16 states, 32 reversible transitions) that show
      the structure to be highly failure resistant against significant partial loss of
      gating function. Rate constants, as fitted in phase plot data of retinal ganglion
      cell excitation, reflect the molecular nature of the gating transitions.
      Additional dimensions (6D cubic diagrams) accommodate kinetically coupled sodium
      inactivation and gating processes associated with beta subunits. The gating
      transitions of coupled sodium inactivation appear to be thermodynamically
      irreversible; response to dielectric surface charges (capacitive displacement)
      provides a potential energy source for those transitions and yields highly energy
      efficient excitation. A comparison of temperature responses of the squid giant
      axon (apparently Arrhenius) and mammalian channel gating yields kinetic Q10 = 2.2
      for alpha unit gating, whose transitions are rate-limiting at mammalian
      temperatures; beta unit kinetic Q10 = 14 reproduces the observed non-Arrhenius
      deviation of mammalian gating at low temperatures; the Q10 of sodium inactivation
      gating matches the rate-limiting component of activation gating at all
      temperatures. The model kinetics reproduce the physiologically large frequency
      range for repetitive firing in ganglion cells and the physiologically observed
      strong temperature dependence of recovery from inactivation. 

PMID- 25867742
TI  - A marching-walking hybrid induces step length adaptation and transfers to natural
      walking.
AB  - Walking is highly adaptable to new demands and environments. We have previously
      studied adaptation of locomotor patterns via a split-belt treadmill, where
      subjects learn to walk with one foot moving faster than the other. Subjects learn
      to adapt their walking pattern by changing the location (spatial) and time
      (temporal) of foot placement. Here we asked whether we can induce adaptation of a
      specific walking pattern when one limb does not "walk" but instead marches in
      place (i.e., marching-walking hybrid). The marching leg's movement is limited
      during the stance phase, and thus certain sensory signals important for walking
      may be reduced. We hypothesized that this would produce a spatial-temporal
      strategy different from that of normal split-belt adaptation. Healthy subjects
      performed two experiments to determine whether they could adapt their spatial
      temporal pattern of step lengths during the marching-walking hybrid and whether
      the learning transfers to over ground walking. Results showed that the hybrid
      group did adapt their step lengths, but the time course of adaptation and
      deadaption was slower than that for the split-belt group. We also observed that
      the hybrid group utilized a mostly spatial strategy whereas the split-belt group
      utilized both spatial and temporal strategies. Surprisingly, we found no
      significant difference between the hybrid and split-belt groups in over ground
      transfer. Moreover, the hybrid group retained more of the learned pattern when
      they returned to the treadmill. These findings suggest that physical
      rehabilitation with this marching-walking paradigm on conventional treadmills may
      produce changes in symmetry comparable to what is observed during split-belt
      training. 

PMID- 25867744
TI  - Hyaluronic Acid as a treatment option for pressure ulcers.
AB  - INTRODUCTION: Health care professionals are constantly seeking novel approaches
      to treat pressure ulcers because of the impact they have on patient quality of
      life and health, as well as the costs associated with treating them. METHODS: A
      review of the literature from 2002-2012 was conducted on the clinical usefulness
      of hyaluronic acid in tissue regeneration. Reports suggest that the therapeutic
      use of hyaluronic acid favors tissue regeneration by modulating the hydration and
      osmotic balance. RESULTS: Different studies show that hyaluronan and derived
      hyaluronic acid products are safe and free of adverse effects. Furthermore, a few
      studies examine the hyaluronic acids repercussions in pressure ulcer treatment.
      CONCLUSION: Reports suggest that this molecule could be successfully used to
      treat pressure ulcers in association with conventional measures.

PMID- 25867745
TI  - A Continuous Bedside Pressure Mapping System for Prevention of Pressure Ulcer
      Development in the Medical ICU: A Retrospective Analysis.
AB  - OBJECTIVE: Patient repositioning to offload high-pressure areas is an essential
      component of pressure ulcer prevention for bed-bound patients. In most settings,
      the quantity and quality of offloading and repositioning are difficult to
      measure. Real-time continuous bedside pressure mapping (CBPM) offers an
      opportunity to do so. MATERIAL AND METHODS: Data was collected on 627 patients
      being treated in a medical intensive care unit (MICU): 307 patients placed on
      beds with a CBPM system and 320 historical controls placed on the same beds
      without the CBPM system 1 year prior to the study participants. A pressure ulcer
      prevention bundle was enhanced by the addition of a CBPM system that provides
      real-time digital imaging of the patient on the support surface to National
      Pressure Ulcer Advisory Panel guidelines. RESULTS: During the 2-month study
      period, 1 (0.3%) patient in the CBPM cohort developed a pressure ulcer compared
      with 16 (5%) patients in the historical cohort (P = 0.001). In a survey of the
      MICU care providers, 90% of respondents reported that the CBPM contributed to
      improved pressure detection and relief, 88% indicated the CBPM assisted them with
      repositioning protocols, and 84% reported the pressure map provided for more
      efficient and effective patient repositioning. CONCLUSION: Real-time, ongoing
      pressure measurement using a pressure-sensing mat may be a useful tool to help
      care providers effectively reposition patients within the context of existing
      standardized protocols for the prevention and minimization of pressure ulcers.   
      .

PMID- 25867746
TI  - Use of a new acellular dermal matrix for treatment of nonhealing wounds in the
      lower extremities of patients with diabetes.
AB  - INTRODUCTION: Acellular dermal matrices (ADMs) have successfully been used in the
      treatment of nonhealing wounds in patients with diabetes. METHODS: A new
      decellularized biological scaffold derived from human skin, D-ADM, (DermACELL,
      LifeNet Health, Virginia Beach, VA), has shown increased cell infiltration, host
      tissue integration, and vascularization in comparison to other ADMs. This
      clinical investigation evaluated the wound closing properties of D-ADM on 18 full
      thickness lower extremity wounds in 15 patients with diabetes over a period of 12
      weeks. RESULTS: A complete wound closure (100% epithelialization) rate of 58%
      (7/12) and an average duration of 10 weeks was demonstrated. Wound healing,
      defined as >= 95% wound closure, was established in 83% of the wounds (10/12) by
      the end of the study treatment. CONCLUSION: These results compare favorably with
      other methods of advanced wound care treatment options that utilize skin
      substitutes to accelerate the healing of difficult-to-treat or chronic wounds.

PMID- 25867743
TI  - Remote limb ischemic conditioning enhances motor learning in healthy humans.
AB  - Brief bouts of sublethal ischemia have been shown to protect exposed tissue
      (ischemic conditioning) and tissues at remote sites (remote ischemic
      conditioning) against subsequent ischemic challenges. Given that the mechanisms
      of this protective phenomenon are multifactorial and epigenetic, we postulated
      that remote limb ischemic conditioning (RLIC) might enhance mechanisms
      responsible for neural plasticity, and thereby facilitate learning. Specifically,
      we hypothesized that conditioning of the nervous system with RLIC, achieved
      through brief repetitive limb ischemia prior to training, would facilitate the
      neurophysiological processes of learning, thus making training more effective and
      more long-lasting. Eighteen healthy adults participated in this study; nine were
      randomly allocated to RLIC and nine to sham conditioning. All subjects underwent
      seven consecutive weekday sessions and 2-wk and 4-wk follow-up sessions. We found
      that RLIC resulted in significantly greater motor learning and longer retention
      of motor performance gains in healthy adults. Changes in motor performance do not
      appear to be due to a generalized increase in muscle activation or muscle
      strength and were not associated with changes in serum brain-derived neurotrophic
      factor (BDNF) concentration. Of note, RLIC did not enhance cognitive learning on
      a hippocampus-dependent task. While future research is needed to establish
      optimal conditioning and training parameters, this inexpensive, clinically
      feasible paradigm might ultimately be implemented to enhance motor learning in
      individuals undergoing neuromuscular rehabilitation for brain injury and other
      pathological conditions. 

PMID- 25867747
TI  - Comparative Efficacy of Silver-Containing Dressing Materials for Treating MRSA
      Infected Wounds in Rats with Streptozotocin-Induced Diabetes.
AB  - OBJECTIVE: Silver plays an important part in severe wound management, mainly by
      reducing microbial growth within dressed wounds and wound beds. However, it is
      unknown how silver-coated dressing materials affect diabetic wounds. The purpose
      of this study is to evaluate the efficacy of silver-containing dressing materials
      for the treatment of methicillin-resistant Staphylococcus aureus (MRSA)-infected
      wounds in streptozotocininduced diabetic rats. METHODS: Full-thickness skin
      defects were created on the backs of rats with streptozotocin (STZ)-induced
      diabetes (n = 108) and were infected with MRSA. The rats were assigned to 6
      groups according to the wound dressing used: nanocrystalline silver (Acticoat,
      Smith & Nephew, Inc, London, UK), silver carboxymethylcellulose (Aquacel-Ag,
      ConvaTec, Skillman, NJ), silver sulfadiazine (Medifoam silver, Genewel Science Co
      Ltd, Seongnam, South Korea), nanocrystalline silver (Poly- Mem silver, Ferris Mfg
      Corp, Burr Ridge, IL), silver sulfadiazine (Ilvadon, Ildong Pharmaceuticals,
      Seoul, South Korea), and 10% povidone iodide (control). The wound size,
      histological findings, and bacterial colony count for each group was analyzed and
      compared to normal Sprague-Dawley rats. RESULTS: Wound size decreased over time
      in every group. On day 10, a significant difference in wound area was detected
      between the silver dressing groups and the control group (P = 0.0040). In the
      wound biopsy, on days 4, 7, and 10, the would-healing effect increased in every
      group. However, between days 4 (P = 0.8250) and 10 (P = 0.9912), there was no
      statistical difference between groups. The number of bacteria in each group
      decreased with time in the bacterial wound culture. The silver dressing groups
      were more effective on antimicrobial efficacy, but there was no statistically
      significant difference between the silver dressing groups and the control group.
      CONCLUSION: Silver-containing dressing materials are an effective method for MRSA
      infected wounds, but nano silver-containing dressing materials did not have
      better results in a diabetic rat model compared to a normal rat model in
      historical review. Further investigation is necessary to determine the relative
      safety of these products on the healing wound. Once that is done, the relative
      value of the products can be determined by balancing their antimicrobial and
      cytotoxicity characteristics.

PMID- 25867748
TI  - Re-examining the automaticity and directionality of the activation of the spatial
      valence "good is up" metaphoric association.
AB  - According to the Conceptual Metaphor Theory, people understand abstract concepts
      depending on the activation of more concrete concepts, but not vice versa. The
      present research aims to investigate the role of directionality and automaticity
      regarding the activation of the conceptual metaphor "good is up". Experiment 1
      tested the automaticity of the spatial-to-valence metaphoric congruency effect by
      having participants judge the valence of a positive or negative word that
      appeared either at the top or at the bottom of the screen. They performed the
      task concurrently with a 6-digit verbal rehearsal task in the working-memory-load
      (WML) blocks and without this task in the non-WML blocks. The spatial-to-valence
      metaphoric congruency effect occurred for the positive words in the non-WML
      blocks (i.e., positive words are judged more quickly when they appeared at the
      top than at the bottom of the screen), but not in the WML blocks, suggesting that
      this metaphoric association might not be activated automatically. Experiments 2-6
      investigated the valence-to-spatial metaphoric association and its automaticity.
      Participants processed a positive or negative prime, which appeared at the center
      of the screen, and then identified a letter (p/q) that subsequently appeared at
      the top or bottom of the screen. The valence-to-spatial metaphoric congruency
      effect did not occur in the WML (6-digit verbal rehearsal) or non-WML blocks,
      whether response modality to the prime was key-press or vocal, or whether the
      prime was a word or a picture. The effect only unexpectedly occurred when the
      task was simultaneously performed with a 4-dot-position visuospatial rehearsal
      task. Nevertheless, the data collapsed across multiple experiments showed a null
      valence-to-spatial metaphoric congruency effect, suggesting the absence of the
      valence-to-spatial metaphoric association in general. The implications of the
      current findings for the Conceptual Metaphor Theory and its alternatives are
      discussed. 

PMID- 25867749
TI  - Analysis of gene expression changes in the rat hippocampus after deep brain
      stimulation of the anterior thalamic nucleus.
AB  - Deep brain stimulation (DBS) surgery, targeting various regions of the brain such
      as the basal ganglia, thalamus, and subthalamic regions, is an effective
      treatment for several movement disorders that have failed to respond to
      medication. Recent progress in the field of DBS surgery has begun to extend the
      application of this surgical technique to other conditions as diverse as morbid
      obesity, depression and obsessive compulsive disorder. Despite these expanding
      indications, little is known about the underlying physiological mechanisms that
      facilitate the beneficial effects of DBS surgery. One approach to this question
      is to perform gene expression analysis in neurons that receive the electrical
      stimulation. Previous studies have shown that neurogenesis in the rat dentate
      gyrus is elicited in DBS targeting of the anterior nucleus of the thalamus(1).
      DBS surgery targeting the ATN is used widely for treatment refractory epilepsy.
      It is thus of much interest for us to explore the transcriptional changes induced
      by electrically stimulating the ATN. In this manuscript, we describe our
      methodologies for stereotactically-guided DBS surgery targeting the ATN in adult
      male Wistar rats. We also discuss the subsequent steps for tissue dissection, RNA
      isolation, cDNA preparation and quantitative RT-PCR for measuring gene expression
      changes. This method could be applied and modified for stimulating the basal
      ganglia and other regions of the brain commonly clinically targeted. The gene
      expression study described here assumes a candidate target gene approach for
      discovering molecular players that could be directing the mechanism for DBS. 

PMID- 25867751
TI  - A microfluidic chip for ICPMS sample introduction.
AB  - This protocol discusses the fabrication and usage of a disposable low cost
      microfluidic chip as sample introduction system for inductively coupled plasma
      mass spectrometry (ICPMS). The chip produces monodisperse aqueous sample droplets
      in perfluorohexane (PFH). Size and frequency of the aqueous droplets can be
      varied in the range of 40 to 60 um and from 90 to 7,000 Hz, respectively. The
      droplets are ejected from the chip with a second flow of PFH and remain intact
      during the ejection. A custom-built desolvation system removes the PFH and
      transports the droplets into the ICPMS. Here, very stable signals with a narrow
      intensity distribution can be measured, showing the monodispersity of the
      droplets. We show that the introduction system can be used to quantitatively
      determine iron in single bovine red blood cells. In the future, the capabilities
      of the introduction device can easily be extended by the integration of
      additional microfluidic modules. 

PMID- 25867752
TI  - Bioinspired Hierarchical Alumina-Graphene Oxide-Poly(vinyl alcohol) Artificial
      Nacre with Optimized Strength and Toughness.
AB  - Due to hierarchical organization of micro- and nanostructures, natural nacre
      exhibits extraordinary strength and toughness, and thus provides a superior model
      for the design and fabrication of high-performance artificial composite
      materials. Although great progress has been made in constructing layered
      composites by alternately stacking hard inorganic platelets and soft polymers,
      the real issue is that the excellent strength of these composites was obtained at
      the sacrifice of toughness. In this work, inspired by the layered aragonite
      microplatelets/chitin nanofibers-protein structure of natural nacre, alumina
      microplatelets-graphene oxide nanosheets-poly(vinyl alcohol) (Al2O3/GO-PVA)
      artificial nacre is successfully constructed through layer-by-layer bottom-up
      assembly, in which Al2O3 and GO-PVA act as "bricks" and "mortar", respectively.
      The artificial nacre has hierarchical "brick-and-mortar" structure and exhibits
      excellent strength (143 +/- 13 MPa) and toughness (9.2 +/- 2.7 MJ/m(3)), which
      are superior to those of natural nacre (80-135 MPa, 1.8 MJ/m(3)). It was
      demonstrated that the multiscale hierarchical structure of ultrathin GO
      nanosheets and submicrometer-thick Al2O3 platelets can deal with the conflict
      between strength and toughness, thus leading to the excellent mechanical
      properties that cannot be obtained using only one size of platelet. We strongly
      believe that the work presented here provides a creative strategy for designing
      and developing new composites with excellent strength and toughness. 

PMID- 25867750
TI  - Phosphorylation at the homotypic interface regulates nucleoprotein
      oligomerization and assembly of the influenza virus replication machinery.
AB  - Negative-sense RNA viruses assemble large ribonucleoprotein (RNP) complexes that
      direct replication and transcription of the viral genome. Influenza virus RNPs
      contain the polymerase, genomic RNA and multiple copies of nucleoprotein (NP).
      During RNP assembly, monomeric NP oligomerizes along the length of the genomic
      RNA. Regulated assembly of the RNP is essential for virus replication, but how NP
      is maintained as a monomer that subsequently oligomerizes to form RNPs is poorly
      understood. Here we elucidate a mechanism whereby NP phosphorylation regulates
      oligomerization. We identified new evolutionarily conserved phosphorylation sites
      on NP and demonstrated that phosphorylation of NP decreased formation of higher
      order complexes. Two phosphorylation sites were located on opposite sides of the
      NP:NP interface. In both influenza A and B virus, mutating or mimicking
      phosphorylation at these residues blocked homotypic interactions and drove NP
      towards a monomeric form. Highlighting the central role of this process during
      infection, these mutations impaired RNP formation, polymerase activity and virus
      replication. Thus, dynamic phosphorylation of NP regulates RNP assembly and
      modulates progression through the viral life cycle. 

PMID- 25867753
TI  - Mesoporous Ge/GeO2/Carbon Lithium-Ion Battery Anodes with High Capacity and High
      Reversibility.
AB  - We report mesoporous composite materials (m-GeO2, m-GeO2/C, and m-Ge-GeO2/C) with
      large pore size which are synthesized by a simple block copolymer directed self
      assembly. m-Ge/GeO2/C shows greatly enhanced Coulombic efficiency, high
      reversible capacity (1631 mA h g(-1)), and stable cycle life compared with the
      other mesoporous and bulk GeO2 electrodes. m-Ge/GeO2/C exhibits one of the
      highest areal capacities (1.65 mA h cm(-2)) among previously reported Ge- and
      GeO2-based anodes. The superior electrochemical performance in m-Ge/GeO2/C arises
      from the highly improved kinetics of conversion reaction due to the synergistic
      effects of the mesoporous structures and the conductive carbon and metallic Ge. 

PMID- 25867754
TI  - Selective reduction in complicated monochorionic twins: prediction of obstetric
      outcome and comparison of techniques.
AB  - OBJECTIVES: To compare the outcomes of radiofrequency ablation (RFA) and bipolar
      cord coagulation (BPC) methods for selective feticide in complicated
      monochorionic (MC) twin gestations and to determine risk factors for adverse
      pregnancy outcome. METHODS: This was a retrospective cohort study of all patients
      with complicated MC twin pregnancy who underwent selective reduction in a single
      tertiary care center between 2000 and 2014. We compared the two methods with
      respect to various demographic, obstetric and perinatal outcome variables.
      RESULTS: Fifty-three selective terminations in complicated MC twin gestations
      were performed, 36 by RFA and 17 by BPC. Each technique resulted in a similar
      overall survival rate of the remaining twin (88.9% vs 76.5%, P = 0.25). Likewise,
      the mean procedure-to-delivery interval, the rate of spontaneous preterm delivery
      < 37, < 34, < 32 and < 28 weeks and the rate of preterm prelabor rupture of the
      membranes did not differ between the groups. However, among patients in the BPC
      group, there was a trend towards earlier gestational age at delivery (31.3 vs
      35.0 weeks, P = 0.09) compared with in the RFA group. There was selective
      reduction by RFA due to selective intrauterine growth restriction (sIUGR) in 19
      cases, 17 (89.5%) of which survived perinatally, with delivery at a median
      gestational age of 37 weeks. There were no significant differences in perinatal
      outcome, irrespective of whether the procedure was performed pre- or post
      viability. All post-viability reductions, most of which were by RFA, resulted in
      perinatal survival. CONCLUSIONS: Perinatal outcome of complicated MC twin
      gestations undergoing selective feticide seems to be similar regardless of
      whether termination is by BPC or RFA. Nevertheless, RFA appears to be
      particularly useful in MC twins complicated by sIUGR and in cases requiring
      selective reduction beyond the age of viability.

PMID- 25867755
TI  - Characterizing aeroallergens by infrared spectroscopy of fungal spores and
      pollen.
AB  - BACKGROUND: Fungal spores and plant pollen cause respiratory diseases in
      susceptible individuals, such as asthma, allergic rhinitis and hypersensitivity
      pneumonitis. Aeroallergen monitoring networks are an important part of treatment
      strategies, but unfortunately traditional analysis is time consuming and
      expensive. We have explored the use of infrared spectroscopy of pollen and spores
      for an inexpensive and rapid characterization of aeroallergens. METHODOLOGY: The
      study is based on measurement of spore and pollen samples by single reflectance
      attenuated total reflectance Fourier transform infrared spectroscopy (SR-ATR
      FTIR). The experimental set includes 71 spore (Basidiomycota) and 121 pollen
      (Pinales, Fagales and Poales) samples. Along with fresh basidiospores, the study
      has been conducted on the archived samples collected within the last 50 years.
      RESULTS: The spectroscopic-based methodology enables clear spectral
      differentiation between pollen and spores, as well as the separation of
      confamiliar and congeneric species. In addition, the analysis of the scattering
      signals inherent in the infrared spectra indicates that the FTIR methodology
      offers indirect estimation of morphology of pollen and spores. The analysis of
      fresh and archived spores shows that chemical composition of spores is well
      preserved even after decades of storage, including the characteristic taxonomy
      related signals. Therefore, biochemical analysis of fungal spores by FTIR could
      provide economical, reliable and timely methodologies for improving fungal
      taxonomy, as well as for fungal identification and monitoring. This proof of
      principle study shows the potential for using FTIR as a rapid tool in
      aeroallergen studies. In addition, the presented method is ready to be
      immediately implemented in biological and ecological studies for direct
      measurement of pollen and spores from flowers and sporocarps.

PMID- 25867756
TI  - MiRNA and TF co-regulatory network analysis for the pathology and recurrence of
      myocardial infarction.
AB  - Myocardial infarction (MI) is a leading cause of death in the world and many
      genes are involved in it. Transcription factor (TFs) and microRNAs (miRNAs) are
      key regulators of gene expression. We hypothesized that miRNAs and TFs might play
      combinatory regulatory roles in MI. After collecting MI candidate genes and
      miRNAs from various resources, we constructed a comprehensive MI-specific miRNA
      TF co-regulatory network by integrating predicted and experimentally validated TF
      and miRNA targets. We found some hub nodes (e.g. miR-16 and miR-26) in this
      network are important regulators, and the network can be severed as a bridge to
      interpret the associations of previous results, which is shown by the case of miR
      29 in this study. We also constructed a regulatory network for MI recurrence and
      found several important genes (e.g. DAB2, BMP6, miR-320 and miR-103), the
      abnormal expressions of which may be potential regulatory mechanisms and markers
      of MI recurrence. At last we proposed a cellular model to discuss major TF and
      miRNA regulators with signaling pathways in MI. This study provides more details
      on gene expression regulation and regulators involved in MI progression and
      recurrence. It also linked up and interpreted many previous results. 

PMID- 25867757
TI  - Method for the assessment of effects of a range of wavelengths and intensities of
      red/near-infrared light therapy on oxidative stress in vitro.
AB  - Red/near-infrared light therapy (R/NIR-LT), delivered by laser or light emitting
      diode (LED), improves functional and morphological outcomes in a range of central
      nervous system injuries in vivo, possibly by reducing oxidative stress. However,
      effects of R/NIR-LT on oxidative stress have been shown to vary depending on
      wavelength or intensity of irradiation. Studies comparing treatment parameters
      are lacking, due to absence of commercially available devices that deliver
      multiple wavelengths or intensities, suitable for high through-put in vitro
      optimization studies. This protocol describes a technique for delivery of light
      at a range of wavelengths and intensities to optimize therapeutic doses required
      for a given injury model. We hypothesized that a method of delivering light, in
      which wavelength and intensity parameters could easily be altered, could
      facilitate determination of an optimal dose of R/NIR-LT for reducing reactive
      oxygen species (ROS) in vitro. Non-coherent Xenon light was filtered through
      narrow-band interference filters to deliver varying wavelengths (center
      wavelengths of 440, 550, 670 and 810 nm) and fluences (8.5x10(-3) to 3.8x10(-1)
      J/cm2) of light to cultured cells. Light output from the apparatus was calibrated
      to emit therapeutically relevant, equal quantal doses of light at each
      wavelength. Reactive species were detected in glutamate stressed cells treated
      with the light, using DCFH-DA and H2O2 sensitive fluorescent dyes. We
      successfully delivered light at a range of physiologically and therapeutically
      relevant wavelengths and intensities, to cultured cells exposed to glutamate as a
      model of CNS injury. While the fluences of R/NIR-LT used in the current study did
      not exert an effect on ROS generated by the cultured cells, the method of light
      delivery is applicable to other systems including isolated mitochondria or more
      physiologically relevant organotypic slice culture models, and could be used to
      assess effects on a range of outcome measures of oxidative metabolism.

PMID- 25867759
TI  - Efinaconazole Topical Solution, 10%: Efficacy in Patients with Onychomycosis and
      Coexisting Tinea Pedis.
AB  - BACKGROUND: We sought to evaluate the efficacy of efinaconazole topical solution,
      10%, in patients with onychomycosis and coexisting tinea pedis. METHODS: We
      analyzed 1,655 patients, aged 18 to 70 years, randomized (3:1) to receive
      efinaconazole topical solution, 10%, or vehicle from two identical multicenter,
      double-blind, vehicle-controlled 48-week studies evaluating safety and efficacy.
      The primary end point was complete cure rate (0% clinical involvement of the
      target toenail and negative potassium hydroxide examination and fungal culture
      findings) at week 52. Three groups were compared: patients with onychomycosis and
      coexisting interdigital tinea pedis on-study (treated or left untreated) and
      those with no coexisting tinea pedis. RESULTS: Treatment with efinaconazole
      topical solution, 10%, was significantly more effective than vehicle use
      irrespective of the coexistence of tinea pedis or its treatment. Overall, 352
      patients with onychomycosis (21.3%) had coexisting interdigital tinea pedis at
      baseline, with 215 of these patients (61.1%) receiving investigator-approved
      topical antifungal agents for their tinea pedis in addition to their randomized
      onychomycosis treatment. At week 52, efinaconazole complete cure rates of 29.4%
      were reported in patients with onychomycosis when coexisting tinea pedis was
      treated compared with 16.1% when coexisting tinea pedis was not treated. Both
      cure rates were significant compared with vehicle (P = .003 and .045,
      respectively), and in the latter subgroup, no patients treated with vehicle
      achieved a complete cure. CONCLUSIONS: Treatment of coexisting tinea pedis in
      patients with onychomycosis enhances the efficacy of once-daily topical treatment
      with efinaconazole topical solution, 10%.

PMID- 25867758
TI  - The sperm ultrastructure and spermiogenesis of Tribolium castaneum (Coleoptera:
      Tenebrionidae) with evidence of cyst degeneration.
AB  - Previous studies on the spermatogenesis of tenebrionid beetles showed the unusual
      formation of two antiparallel sperm bundles per cyst. In this work we reported
      this feature also in Tribolium castaneum using light and transmission electron
      microscopy. The sperm structure of T. castaneum, similar to other tenebrionids,
      consists of a three-layered acrosome, an elongated nucleus and a flagellum with a
      9+9+2 axoneme, two accessory bodies and two asymmetric mitochondrial derivatives.
      The presence of two antiparallel sperm bundles per cyst also in Meloidae and
      Rhipiphoridae suggests that it is a strong trait synapomorphic for
      Tenebrionoidea. The huge degeneration of whole sperm cells in several cysts of
      testes during spermiogenesis is also described. 

PMID- 25867760
TI  - Cryptogenic Stroke: Making the Management Less Cryptic.
AB  - Cryptogenic stroke (CS) accounts for 20% to 40% of ischemic strokes. CS is
      defined as a cortical infarct suggestive of an embolic stroke with no
      identifiable cardiac etiology, large vessel occlusive disease, or small vessel
      lacunar stroke. The likely etiologies for CS are patent foramen ovale (PFO) and
      paroxysmal atrial fibrillation, which can be detected by transesophageal
      echocardiography and long-term cardiac rhythm monitoring. In a busy academic
      hospital, the stroke service is frequently asked to provide a rational approach
      to patients with such a presentation. The 2011 American Heart
      Association/American Stroke Association recommends that antiplatelet therapy is
      "reasonable" (Class IIa; Level of Evidence B) for patients with PFO and a
      clinical presentation of CS. Confounding PFO management is the lack of a
      controlled trial comparing anticoagulation with antiplatelet therapy in patients
      with CS, despite the belief that the primary mechanism of PFO-mediated stroke
      would be that it serves as a conduit for venous emboli. Data from 3 recent
      prospective PFO closure device trials further compound the management protocols
      for these patients. Also complicating the management of CS is increasing evidence
      that paroxysmal atrial fibrillation may be found as often as 30% with extensive
      monitoring and long-term follow-up of 36 months. Based on these recent
      developments, we summarize the factors that we deemed relevant in our approach to
      patients with CS. 

PMID- 25867761
TI  - Aspirin blocks growth of breast tumor cells and tumor-initiating cells and
      induces reprogramming factors of mesenchymal to epithelial transition.
AB  - Acetylsalicylic acid (ASA), also known as aspirin, a classic, nonsteroidal, anti
      inflammatory drug (NSAID), is widely used to relieve minor aches and pains and to
      reduce fever. Epidemiological studies and other experimental studies suggest that
      ASA use reduces the risk of different cancers including breast cancer (BC) and
      may be used as a chemopreventive agent against BC and other cancers. These
      studies have raised the tempting possibility that ASA could serve as a preventive
      medicine for BC. However, lack of in-depth knowledge of the mechanism of action
      of ASA reshapes the debate of risk and benefit of using ASA in prevention of BC.
      Our studies, using in vitro and in vivo tumor xenograft models, show a strong
      beneficial effect of ASA in the prevention of breast carcinogenesis. We find that
      ASA not only prevents breast tumor cell growth in vitro and tumor growth in nude
      mice xenograft model through the induction of apoptosis, but also significantly
      reduces the self-renewal capacity and growth of breast tumor-initiating cells
      (BTICs)/breast cancer stem cells (BCSCs) and delays the formation of a palpable
      tumor. Moreover, ASA regulates other pathophysiological events in breast
      carcinogenesis, such as reprogramming the mesenchymal to epithelial transition
      (MET) and delaying in vitro migration in BC cells. The tumor growth-inhibitory
      and reprogramming roles of ASA could be mediated through inhibition of TGF
      beta/SMAD4 signaling pathway that is associated with growth, motility, invasion,
      and metastasis in advanced BCs. Collectively, ASA has a therapeutic or preventive
      potential by attacking possible target such as TGF-beta in breast carcinogenesis.

PMID- 25867762
TI  - Development and characterization of human-induced pluripotent stem cell-derived
      cholangiocytes.
AB  - Cholangiocytes are the target of a heterogeneous group of liver diseases known as
      the cholangiopathies. An evolving understanding of the mechanisms driving biliary
      development provides the theoretical underpinnings for rational development of
      induced pluripotent stem cell (iPSC)-derived cholangiocytes (iDCs). Therefore,
      the aims of this study were to develop an approach to generate iDCs and to fully
      characterize the cells in vitro and in vivo. Human iPSC lines were generated by
      forced expression of the Yamanaka pluripotency factors. We then pursued a
      stepwise differentiation strategy toward iDCs, using precise temporal exposure to
      key biliary morphogens, and we characterized the cells, using a variety of
      morphologic, molecular, cell biologic, functional, and in vivo approaches.
      Morphology shows a stepwise phenotypic change toward an epithelial monolayer.
      Molecular analysis during differentiation shows appropriate enrichment in markers
      of iPSC, definitive endoderm, hepatic specification, hepatic progenitors, and
      ultimately cholangiocytes. Immunostaining, western blotting, and flow cytometry
      demonstrate enrichment of multiple functionally relevant biliary proteins. RNA
      sequencing reveals that the transcriptome moves progressively toward that of
      human cholangiocytes. iDCs generate intracellular calcium signaling in response
      to ATP, form intact primary cilia, and self-assemble into duct-like structures in
      three-dimensional culture. In vivo, the cells engraft within mouse liver,
      following retrograde intrabiliary infusion. In summary, we have developed a novel
      approach to generate mature cholangiocytes from iPSCs. In addition to providing a
      model of biliary differentiation, iDCs represent a platform for in vitro disease
      modeling, pharmacologic testing, and individualized, cell-based, regenerative
      therapies for the cholangiopathies. 

PMID- 25867763
TI  - Phenotypic diversity of patient-derived melanoma populations in stem cell medium.
AB  - Melanomas are highly heterogeneous tumors and there is no treatment effective at
      achieving long-term remission for metastatic melanoma patients. Thus, an
      appropriate model system for studying melanoma biology and response to drugs is
      necessary. It has been shown that composition of the medium is a critical factor
      in preserving the complexity of the tumor in in vitro settings, and melanospheres
      maintained in stem cell medium are a good model in this respect. In the present
      study, we observed that not all nodular melanoma patient-derived cell populations
      grown in stem cell medium were capable of forming melanospheres, and cell
      aggregates and anchorage-independent single-cell cultures emerged instead. Self
      renewing capacity and unlimited growth potential indicated the presence of cells
      with stem-like properties in all patient-derived populations but immunophenotype
      and MITF expression exhibited variability. Enhanced MITF expression and activity
      was observed in melanospheres in comparison with cell aggregates and single-cell
      culture, and hypoxic-like conditions that increased the ability of single-cell
      population to form melanospheres enhanced MITF expression and cell pigmentation
      as well. Thus, MITF seems to be a critical transcription factor for formation of
      both patient-derived and hypoxia-induced melanospheres. After 2 years of
      continuous culturing, melanospheres progressively underwent transition into cell
      aggregates that was accompanied by changes in expression of several MITF
      dependent genes associated with melanogenesis and survival and alterations in the
      composition of subpopulations but not in the frequency of ABCB5-positive cells.
      Several biological properties of parent tumor are well preserved in patient
      derived melanospheres, but during prolonged culturing the heterogeneity is
      substantially lost when the melanospheres are substituted by cell aggregates.
      This should be considered when cell aggregates instead of melanospheres are used
      in the study of melanoma biology and cell response to drugs. 

PMID- 25867764
TI  - RNA sequencing of sarcomas with simple karyotypes: identification and enrichment
      of fusion transcripts.
AB  - Gene fusions are neoplasia-associated mutations arising from structural
      chromosomal rearrangements. They have a strong impact on tumor development and
      constitute important diagnostic markers. Malignant soft tissue tumors (sarcomas)
      constitute a heterogeneous group of neoplasms with >50 distinct subtypes, each of
      which is rare. In addition, there is considerable morphologic overlap between
      sarcomas and benign lesions. Several subtypes display distinct gene fusions,
      serving as excellent biomarkers. The development of methods for deep sequencing
      of the complete transcriptome (RNA-Seq) has substantially improved the
      possibilities for detecting gene fusions. With the aim of identifying new gene
      fusions of biological and clinical relevance, eight sarcomas with simple
      karyotypes, ie, only one or a few structural rearrangements, were subjected to
      massively parallel paired-end sequencing of mRNA. Three different algorithms were
      used to identify fusion transcripts from RNA-Seq data. Three novel (KIAA2026
      NUDT11, CCBL1-ARL1, and AFF3-PHF1) and two previously known fusions (FUS-CREB3L2
      and HAS2-PLAG1) were found and could be verified by other methods. These findings
      show that RNA-Seq is a powerful tool for detecting gene fusions in sarcomas but
      also suggest that it is advisable to use more than one algorithm to analyze the
      output data as only two of the confirmed fusions were reported by more than one
      of the gene fusion detection software programs. For all of the confirmed gene
      fusions, at least one of the genes mapped to a chromosome band implicated by the
      karyotype, suggesting that sarcomas with simple karyotypes constitute an
      excellent resource for identifying novel gene fusions. 

PMID- 25867765
TI  - CDX2 homeoprotein is involved in the regulation of ST6GalNAc-I gene in intestinal
      metaplasia.
AB  - De novo expression of Sialyl-Tn (STn) antigen is one of the most common features
      of intestinal metaplasia (IM) and gastric carcinomas, and its biosynthesis has
      been mostly attributed to ST6GalNAc-I activity. However, the regulation of this
      glycosyltransferase expression is not elucidated. In IM lesions and in the
      intestine, CDX2 homeobox transcription factor is co-expressed with STn and
      ST6GalNAc-I. We therefore hypothesized that CDX2 might induce STn expression by
      positive regulation of ST6GalNAc-I. We showed that ST6GalNAc-I transcript levels
      and CDX2 have a coordinated expression upon Caco-2 in vitro differentiation, and
      overexpression of CDX2 in MKN45 gastric cells increases ST6GalNAc-I transcript
      levels. Nine putative CDX-binding sites in the ST6GalNAc-I-regulatory sequence
      were identified and analyzed by chromatin immunoprecipitation in Caco-2 cells and
      in IM. The results showed that CDX2 protein is recruited to all regions, being
      the most proximal sites preferentially occupied in vivo. Luciferase assays
      demonstrated that CDX2 is able to transactivate ST6GalNac-I-regulatory region.
      The induction was stronger for the regions mapped in the neighbourhood of ATG
      start codon and site-directed mutagenesis of these sites confirmed their
      importance. In conclusion, we show that CDX2 transcriptionally regulates
      ST6GalNAc-I gene expression, specifically in the preneoplastic IM lesion. 

PMID- 25867766
TI  - Osteopontin depletion decreases inflammation and gastric epithelial proliferation
      during Helicobacter pylori infection in mice.
AB  - Osteopontin (OPN) is a multifunctional protein that plays a role in many
      physiological and pathological processes, including inflammation and
      tumorigenesis. Here, we investigated the involvement of OPN in Helicobacter
      pylori (HP)-induced gastritis using OPN knockout (KO) mice and OPN knockdown (KD)
      cell lines. HP-infected OPN KO mice showed significantly reduced gastritis
      compared with wild-type (WT) mice with decreased infiltration of macrophages and
      a reduction in HP-induced upregulation of IL-1beta, TNF-alpha, and IFN-gamma. HP
      exposed OPN KD gastric cancer cells and macrophage-like cells showed an
      attenuated induction of these cytokines. We also demonstrated a reduction in the
      migration of monocytic and macrophage-like cells toward conditioned media
      harvested from HP-exposed OPN KD gastric cancer cells as well as reduced
      migration ability of OPN KD cells itself. In addition, HP-infected OPN KO mice
      showed decreased epithelial cell proliferation compared with HP-infected WT mice,
      in association with a reduction in MAPK pathway activation. OPN KD gastric cancer
      cell lines also showed lower proliferative activity and reduced MAPK activation
      than shRNA control cells after HP co-culture or after IL-1beta and TNF-alpha
      treatment. Taken together, these results indicate that OPN exerts a considerable
      influence on HP-induced gastritis by modulating the production of cytokines and
      contributing to macrophage infiltration. Moreover, OPN-mediated activation of the
      MAPK pathway in gastric epithelial cells might contribute to epithelial changes
      following HP infection. 

PMID- 25867767
TI  - Formalin-fixed, paraffin-embedded (FFPE) tissue epigenomics using Infinium
      HumanMethylation450 BeadChip assays.
AB  - Current genome-wide methods to detect DNA-methylation in healthy and diseased
      tissue require high-quality DNA from fresh-frozen (FF) samples. However, well
      annotated clinical samples are mostly available as formalin-fixed, paraffin
      embedded (FFPE) tissues containing poor-quality DNA. To overcome this limitation,
      we here aimed to evaluate a DNA restoration protocol for usage with the genome
      wide Infinium HumanMethylation450 BeadChip assay (HM-450K). Sixty-six DNA samples
      from normal colon (n=9) and breast cancer (n=11) were interrogated separately
      using HM-450K. Analyses included matched FF/FFPE samples and technical
      duplicates. FFPE DNA was processed with (FFPEr) or without a DNA restoration
      protocol (Illumina). Differentially methylated genes were finally validated in 24
      additional FFPE tissues using nested methylation-specific PCR (MSP). In summary,
      beta-values correlation between FFPEr duplicates was high (rho=0.9927 (s.d. +/
      0.0015)). Matched FF/FFPEr correlation was also high (rho=0.9590 (s.d. +/
      0.0184)) compared with matched FF/FFPE (rho=0.8051 (s.d. +/-0.1028). Probe
      detection rate in FFPEr samples (98.37%, s.d. +/-0.66) was comparable to FF
      samples (99.98%, s.d. +/-0.019) and substantially lower in FFPE samples (82.31%,
      s.d. +/-18.65). Assay robustness was not decreased by sample archival age up to
      10 years. We could also demonstrate no decrease in assay robustness when using
      100 ng of DNA input only. Four out of the five selected differentially methylated
      genes could be validated by MSP. The gene failing validation by PCR showed high
      variation of CpG beta-values in primer-binding sites. In conclusion, by using the
      FFPE DNA restoration protocol, HM-450K assays provide robust, accurate and
      reproducible results with FFPE tissue-derived DNA, which are comparable to those
      obtained with FF tissue. Most importantly, differentially methylated genes can be
      validated using more sensitive techniques, such as nested MSP, altogether
      providing an epigenomics platform for molecular pathological epidemiology
      research on archived samples with limited tissue amount. 

PMID- 25867768
TI  - High-mobility group box 1 accelerates lipopolysaccharide-induced lung fibroblast
      proliferation in vitro: involvement of the NF-kappaB signaling pathway.
AB  - The mechanism underlying lipopolysaccharide (LPS)-induced aberrant proliferation
      of lung fibroblasts in Gram-negative bacilli-associated pulmonary fibrosis is
      unknown. High-mobility group box 1 (HMGB1) is a ubiquitous nuclear protein that
      is released from the nuclei of lung fibroblasts after LPS stimulation. It can
      exasperate LPS-induced inflammation and hasten cell proliferation. Thus, this
      study investigated the effects of LPS- and/or HMGB1-stimulating murine lung
      fibroblasts on gene expression using various assays in vitro. Thiazolyl-diphenyl
      tetrazolium bromide (MTT) assay data showed that either LPS or HMGB1 could induce
      lung fibroblast proliferation. Endogenous HMGB1 secreted from lung fibroblasts
      was detected by enzyme-linked immunosorbent assay (ELISA) 48 h after LPS
      stimulation. Pretreatment with an anti-HMGB1 antibody inhibited the proliferative
      effects of LPS on lung fibroblasts. DNA microarray data showed that the NF-kappaB
      signaling genes were upregulated in cells after stimulated with LPS, HMGB1, or
      both. Secretion of matrix metalloproteinase (MMP)-2 and MMP-9, and tissue
      inhibitor of metalloproteinase 2 (TIMP-2) was significantly upregulated after
      treatment with LPS, HMGB1, or their combination. However, an NF-kappaB inhibitor
      was able to downregulate levels of these proteins. In addition, levels of Toll
      like receptor 4 (TLR4), Toll-like receptor 2 (TLR2), and receptors for advanced
      glycation end products (RAGE) mRNA and proteins were also upregulated in these
      cells after LPS treatment and further upregulated by LPS plus HMGB1. In
      conclusion, the data from the current study demonstrate that LPS-induced lung
      fibroblast secretion of endogenous HMGB1 can augment the proproliferative effects
      of LPS and, therefore, may play a key role in exacerbation of pulmonary fibrosis.
      The underlying molecular mechanisms are related to the activation of the TLR4/NF
      kappaB signaling pathway and its downstream targets. 

PMID- 25867769
TI  - Chronic traumatic encephalopathy: A paradigm in search of evidence?
AB  - Chronic traumatic encephalopathy (CTE) has been in the medical literature since
      the 1920s. It is characterized clinically by diverse neuropsychiatric symptoms,
      and pathologically by variable degrees of phosphorylated tau accumulation in the
      brain. The evolving paradigm for the pathogenesis of CTE suggests that concussion
      or subconcussion from athletic participation initiates a cascade of pathologic
      events, encompassing neuroinflammation and protein templating with trans-synaptic
      neurotoxicity. The end result is neurologic and neurobehavioral deterioration,
      often with self-harm. Although these concepts warrant further investigation, the
      available evidence permits no conclusions as regards the pathogenesis of the
      reported findings. Investigations into the role of premorbid or co-morbid
      neurodegenerative diseases has been limited to date, and in-depth genetic
      analyses have not been performed. The role of concussion or subconcussion if any,
      whether and how the condition progresses over time, the extent of phosphorylated
      tau in clinically normal athletes, the role of phosphorylated tau as a toxic
      species versus an inert disease response, and whether protein templating has any
      in vivo relevance remain to be elucidated. 

PMID- 25867770
TI  - Prospective population-based cohort of inflammatory bowel disease in the
      biologics era: Disease course and predictors of severity.
AB  - BACKGROUND AND AIM: We have previously found high incidence of inflammatory bowel
      disease (IBD) in Australia. A population-based registry was established to assess
      disease severity, frequency of complications, and prognostic factors. METHODS:
      Incident cases were prospectively identified over 4 years. Early disease severity
      was assessed according to need for hospitalization and resective surgery and
      medication use. RESULTS: We report on the early outcomes (median 18 months, range
      12-60 months) for 252 patients comprising 146 with Crohn's disease (CD), 96 with
      ulcerative colitis (UC), and 10 IBD undifferentiated. Eighty-seven percent of CD
      patients had inflammatory disease at diagnosis, and this reduced to 73% at 5
      years (n = 38). Immunomodulators were prescribed in 57% of CD patients and 19%
      with UC. A third of all CD patients were hospitalized, the majority (77%) in the
      first 12 months. Risk factors for hospitalization included penetrating, perianal,
      and ileocolonic disease (P < 0.05). Twenty-four percent of UC patients were
      hospitalized, most within the first 12 months. Intestinal resection rates were
      13% at 1 year in CD and 26% at 5 years. Risk factors include penetrating and
      stricturing disease (P < 0.001) and ileal involvement (P < 0.05). Colectomy rates
      in UC were 2% and 13% at 1 and 5 years. High C-reactive protein (CRP) at
      diagnosis was associated with colectomy. CONCLUSIONS: A high rate of inflammatory
      disease, frequent immunomodulator use in CD, and a low rate of surgery in both CD
      and UC were identified. In CD, ileal involvement and complex disease behavior are
      associated with a more severe disease course, while in UC a high CRP predicted
      this outcome.

PMID- 25867771
TI  - Vildagliptin versus insulin in patients with type 2 diabetes mellitus
      inadequately controlled with sulfonylurea: results from a randomized, 24 week
      study.
AB  - OBJECTIVE: There is limited evidence to guide the selection of second-line anti
      hyperglycemic agents in patients with type 2 diabetes mellitus (T2DM) who are
      inadequately controlled with sulfonylurea monotherapy and are intolerant to
      metformin. We compared the efficacy and safety of vildagliptin 50 mg qd and
      Neutral Protamine Hagedorn (NPH) insulin qd in such patients. METHODS: This was a
      24 week, multicenter, randomized, open-label study. The co-primary endpoints were
      (i) proportion of patients achieving HbA1c <7.0% without any confirmed
      hypoglycemic events (HEs) or weight gain >=3% (composite endpoint); (ii) rate of
      confirmed HEs. Treatment satisfaction was assessed using the TSQM-9 questionnaire
      at study end. RESULTS: A total of 162 patients were randomly assigned to
      vildagliptin (n = 83) and NPH insulin (n = 79). Similar proportion of patients
      achieved the composite endpoint in vildagliptin versus NPH insulin group (35.4%
      versus 34.2%; OR 0.985; 95% CI 0.507, 1.915; p = 0.96). After 24 weeks, 48.8% of
      patients in the vildagliptin group and 60.8% in the NPH insulin group achieved
      HbA1c <7.0%; 13.4% in the vildagliptin group and 29.1% in the insulin group had
      at least one confirmed HE; while 11.0% in the vildagliptin group and 22.8% in the
      insulin group experienced weight gain. The rate of confirmed HEs was
      significantly lower in patients receiving vildagliptin versus NPH insulin (1.3
      versus 5.1 events per year). The TSQM-9 score for 'convenience' at week 24
      increased significantly more with vildagliptin than with NPH insulin.
      CONCLUSIONS: Addition of vildagliptin and NPH insulin resulted in a similar
      number of patients reaching HbA1c target without HEs or weight gain in T2DM
      patients inadequately controlled with sulfonylurea. The addition of vildagliptin
      to sulfonylurea could be considered as a treatment option prior to
      intensification with insulin, with the advantages of a lower HE rate and greater
      patient convenience. Study results are limited by a higher drop-out rate in the
      vildagliptin arm.

PMID- 25867772
TI  - The method quality of cross-over studies involved in Cochrane Systematic Reviews.
AB  - BACKGROUND: It is possible that cross-over studies included in current systematic
      reviews are being inadequately assessed, because the current risk of bias tools
      do not consider possible biases specific to cross-over design. We performed this
      study to evaluate whether this was being done in cross-over studies included in
      Cochrane Systematic Reviews (CSRs). METHODS: We searched the Cochrane Library (up
      to 2013 issue 5) for CSRs that included at least one cross-over trial. Two
      authors independently undertook the study selection and data extraction. A random
      sample of the CSRs was selected and we evaluated whether the cross-over trials in
      these CSRs were assessed according to criteria suggested by the Cochrane
      handbook. In addition we reassessed the risk of bias of these cross-over trials
      by a checklist developed form the Cochrane handbook. RESULTS: We identified 688
      CSRs that included one or more cross-over studies. We chose a random sample of 60
      CSRs and these included 139 cross-over studies. None of these CSRs undertook a
      risk of bias assessment specific for cross-over studies. In fact items specific
      for cross-over studies were seldom considered anywhere in quality assessment of
      these CSRs. When we reassessed the risk of bias, including the 3 items specific
      to cross-over trials, of these 139 studies, a low risk of bias was judged for
      appropriate cross-over design in 110(79%), carry-over effects in 48(34%) and for
      reporting data in all stages of the trial in 114(82%).Assessment of biases in
      cross-over trials could affect the GRADE assessment of a review's findings.
      CONCLUSION: The current Cochrane risk of bias tool is not adequate to assess
      cross-over studies. Items specific to cross-over trials leading to potential risk
      of bias are generally neglected in CSRs. A proposed check list for the evaluation
      of cross-over trials is provided.

PMID- 25867773
TI  - Addressing the challenges of the HIV continuum of care in high-prevalence cities
      in the United States.
AB  - In summary, addressing the challenges of the HIV care continuum is critical so
      that the goals of the NHAS can be achieved. CDC is working closely with federal
      partners, public health departments, and communities throughout the United States
      on multiple surveillance, programmatic, and research initiatives to inform and
      improve outcomes along the HIV care continuum. Currently, a large number of
      research projects are being conducted to describe the care continuum in various
      populations, assess and model the impact of interventions, and monitor the
      quality of care. To contribute to this knowledge base, NIH is working with its
      academic partners to support research that will inform the optimization of HIV
      treatment and prevention programs. As part of this focus, the CFAR/APC HIV
      Continuum of Care Working Group was formed to encourage communication between
      academic investigators and their local DOHs and to support joint research
      initiatives that are both timely and relevant to their own cities and
      environments. Finally, the results presented in this supplement may have
      implications for jurisdictions beyond those in which the studies were conducted.

PMID- 25867774
TI  - Barriers and facilitators to engagement of vulnerable populations in HIV primary
      care in New York City.
AB  - BACKGROUND: Engagement in HIV care helps to maximize viral suppression, which in
      turn, reduces morbidity and mortality and prevents further HIV transmission. With
      more HIV cases than any other US city, New York City reported in 2012 that only
      41% of all persons estimated to be living with HIV (PLWH) had a suppressed viral
      load, whereas nearly three-quarters of those in clinical care achieved viral
      suppression. Thus, retaining PLWH in HIV care addresses this central goal of both
      the US National HIV/AIDS Strategy and Governor Cuomo's plan to end the AIDS
      epidemic in New York State. METHODS: We conducted 80 in-depth qualitative
      interviews with PLWH in 4 New York City populations that were identified as being
      inconsistently engaged in HIV medical care: African immigrants, previously
      incarcerated adults, transgender women, and young men who have sex with men.
      RESULTS: Barriers to and facilitators of HIV care engagement fell into 3 domains:
      (1) system factors (eg, patient-provider relationship, social service agencies,
      transitions between penal system and community), (2) social factors (eg, family
      and other social support; stigma related to HIV, substance use, sexual
      orientation, gender identity, and incarceration), and (3) individual factors (eg,
      mental illness, substance use, resilience). Similarities and differences in these
      themes across the 4 populations as well as research and public health
      implications were identified. CONCLUSIONS: Engagement in care is maximized when
      the social challenges confronted by vulnerable groups are addressed, patient
      provider communication is strong, and coordinated services are available,
      including housing, mental health and substance use treatment, and peer
      navigation.

PMID- 25867775
TI  - Assessing the use of HIV surveillance data to help gauge patient retention-in
      care.
AB  - BACKGROUND: Improved retention-in-care may enhance health outcomes for people
      living with HIV/AIDS (PLWHA). Although laboratory surveillance data may be used
      to gauge retention, no previous reports have compared laboratory surveillance vs.
      clinic visit-based measures of retention-in-care. We compared laboratory
      surveillance vs. clinic visit-based approaches for identifying retention status
      for PLWHA. METHODS: We examined 2011 patient visit data from the Ruth M.
      Rothstein CORE Center, Cook County's HIV clinic. We defined retained patients as
      those with visits every 6 months over 2 years and matched patients classified
      through visit data against HIV surveillance laboratories reported to the Chicago
      Department of Health. We determined the sensitivity, specificity, and receiver
      operator characteristics of varying laboratory surveillance vs. clinic visit
      measures of retention. RESULTS: Of patients classified through clinic visit data,
      91% of 1714 in-care vs. 22% of 200 out-of-care patients met our most stringent
      surveillance-based retention definition-having >=2 viral load/CD4s performed 90
      days apart reported by the same laboratory in 2011. Of surveillance laboratory
      based definitions for retention, having >=2 HIV viral load and/or CD4 values at
      least 3 months apart reported from the same facility possessed the best receiver
      operator parameters and the receiver operator characteristics' curve comparing
      several laboratory surveillance vs. clinic visit-based retention measures that
      had an area under the curve of 0.95. CONCLUSIONS: Our findings demonstrate that
      surveillance laboratory data can be used to assess retention-in-care for PLWHA.
      These data suggest that bi-directional data sharing between public health
      entities and care providers could advance re-engagement efforts.

PMID- 25867776
TI  - Acceptance of the use of HIV surveillance data for care engagement: national and
      local community perspectives.
AB  - BACKGROUND: Use of surveillance data including laboratory results (e.g., CD4 and
      HIV RNA) by public health departments to facilitate linkage, retention, and
      reengagement of HIV-infected individuals in health care is on the rise. This is
      part of the goal of increasing the proportion of infected persons achieving
      virologic suppression. However, this use of surveillance data is not without
      controversy, particularly among some providers and people living with HIV.
      METHODS: We conducted informal discussions with key stakeholders and a literature
      search and held a national think tank in November 2012, bringing together 31
      representatives of the federal government, county and state officials, health
      care providers, and community-based organizations. A follow-up community
      consultation specific to San Francisco was held January 24, 2014, with 10
      participants. Notes from these activities were used as data for this analysis.
      RESULTS: The think tank identified 3 strategies using HIV surveillance data to
      aid in care engagement: (1) provider-mediated, where health department staff work
      with the provider of record on reengagement, (2) electronic linkages between
      surveillance databases and medical records databases, and (3) direct outreach,
      where trained health department staff reach out to persons out of care.
      Participants also developed recommendations for minimizing harm, guidance on
      meaningful stakeholder involvement, and a consensus statement in support of the
      use of HIV surveillance data in care engagement. CONCLUSIONS: Acceptance of the
      use of surveillance data for HIV care linkage, retention, and reengagement is
      achievable, particularly if stakeholders have been engaged in the design,
      conduct, and evaluation of programs.

PMID- 25867777
TI  - Individual and community factors associated with geographic clusters of poor HIV
      care retention and poor viral suppression.
AB  - BACKGROUND: Previous analyses identified specific geographic areas in
      Philadelphia (hotspots) associated with negative outcomes along the HIV care
      continuum. We examined individual and community factors associated with residing
      in these hotspots. METHODS: Retrospective cohort of 1404 persons newly diagnosed
      with HIV in 2008-2009 followed for 24 months after linkage to care. Multivariable
      regression examined associations between individual (age, sex, race/ethnicity,
      HIV transmission risk, and insurance status) and community (economic deprivation,
      distance to care, access to public transit, and access to pharmacy services)
      factors and the outcomes: residence in a hotspot associated with poor retention
      in-care and residence in a hotspot associated with poor viral suppression.
      RESULTS: In total, 24.4% and 13.7% of persons resided in hotspots associated with
      poor retention and poor viral suppression, respectively. For persons residing in
      poor retention hotspots, 28.3% were retained in care compared with 40.4% of those
      residing outside hotspots (P < 0.05). Similarly, for persons residing in poor
      viral suppression hotspots, 51.4% achieved viral suppression compared with 75.3%
      of those outside hotspots (P < 0.0.05). Factors significantly associated with
      residence in poor retention hotspots included female sex, lower economic
      deprivation, greater access to public transit, shorter distance to medical care,
      and longer distance to pharmacies. Factors significantly associated with
      residence in poor viral suppression hotspots included female sex, higher economic
      deprivation, and shorter distance to pharmacies. CONCLUSIONS: Individual and
      community-level associations with geographic hotspots may inform both content and
      delivery strategies for interventions designed to improve retention-in-care and
      viral suppression.

PMID- 25867778
TI  - Sorting through the lost and found: are patient perceptions of engagement in care
      consistent with standard continuum of care measures?
AB  - BACKGROUND: Indicators for determining one's status on the HIV care continuum are
      often measured using clinical and surveillance data but do not typically assess
      patient perspectives. We assessed patient-reported care status along the care
      continuum and whether it differed from medical records and surveillance data.
      METHODS: Between June 2013 and October 2014, a convenience sample of clinic
      attending HIV-infected persons was surveyed regarding care-seeking behaviors and
      self-perceived status along the care continuum. Participant responses were
      matched to DC Department of Health surveillance data and clinic records.
      Participants' care patterns were classified using Health Resources Services
      Administration-defined care status: in care (IC), sporadic care (SC), or out of
      care (OOC). Semistructured qualitative interviews were analyzed using an open
      coding process to elucidate relevant themes regarding participants' perceptions
      of engagement in care. RESULTS: Of 169 participants, most were male participants
      (64%) and black (72%), with a mean age of 50.7 years. Using self-reported visit
      patterns, 115 participants (68%) were consistent with being IC, 33 (20%) SC, and
      21 (12%) OOC. Among OOC participants, 52% perceived themselves to be fully
      engaged in HIV care. In the previous year, among OOC participants, 71% reported
      having a non-HIV-related medical visit and 90% reported current antiretroviral
      use. Qualitatively, most SC and OOC persons did not see their HIV providers
      regularly because they felt healthy. CONCLUSIONS: Participants' perceptions of
      HIV care engagement differed from actual care receipt as measured by surveillance
      and clinical records. Measures of care engagement may need to be reconsidered as
      persons not receiving regular HIV care maybe accessing other health care and HIV
      medications elsewhere.

PMID- 25867779
TI  - Examining clinic-based and public health approaches to ascertainment of HIV care
      status.
AB  - INTRODUCTION: Clinic-based tracing efforts and public health surveillance data
      can provide different information about HIV care status for the same patients.
      The relative yield and how best to use these sources to identify and reengage out
      of-care patients is unknown. METHODS: At a large public HIV clinic in San
      Francisco, we selected a 10% random sample of active patients who were at least
      210 days "late" for an HIV primary care visit as of April 1, 2013, for clinic
      based outreach. Patients were considered out of care if they did not have an HIV
      primary care visit in the 210 days before April 1, 2013. We then matched the
      sample with the San Francisco Department of Public Health HIV surveillance
      registry. Patients with a CD4 or viral load result in the 210-day period were
      classified as in care. We compared results from both sources and estimated the
      cumulative incidence of disengagement from care for the full cohort of clinic
      patients. RESULTS: Of 940 patients lost to follow-up, 95 were sampled. Clinic
      tracing found 60 (63%) in care, 23 (24%) not located, 9 (10%) out of care, 2 (2%)
      incarcerated, and 1 (1%) had died. Of 42 individuals surveillance classified as
      out of care, tracing found 22 (52%) were in care. Of 52 patients found to be in
      care by surveillance, 12 (23%) were out of care by clinic tracing or unable to be
      located. The naive estimate of the cumulative incidence of disengagement from
      care at 3 years for the active clinic cohort was 41.1% [95% confidence interval
      (CI): 37.6 to 44.5]. The use of surveillance data reduced this estimate to 12.7%
      (95% CI: 18.2 to 25.4), and when further corrected using tracing outcomes, the
      estimate dropped to only 6.4% (95% CI: 3.4 to 9.4). CONCLUSIONS: Clinic-based
      tracing and surveillance data together provide a better understanding of care
      status than either method alone. Using surveillance data to inform clinic-based
      outreach efforts may be an effective strategy, although tracing efforts are most
      likely to be successful if conducted in real time.

PMID- 25867780
TI  - Association of individual and systemic barriers to optimal medical care in people
      living with HIV/AIDS in Miami-Dade County.
AB  - Barriers to retention in HIV care are detrimental to patients' progress along the
      HIV continuum of care. Previous literature has focused on individual, client
      level barriers, and interventions to address them. In contrast, less work has
      examined the role of system-level barriers on HIV care outcomes. This study seeks
      to understand how individual and systemic barriers individually are associated
      with clinic appointment attendance and virologic suppression in HIV-infected
      patients attending the largest HIV clinic in Miami-Dade, FL. In addition, we
      examined the synergistic effects of these barriers as potential syndemic factors
      on these health outcomes. Barriers to clinic attendance were determined in a face
      to-face study interview with 444 HIV-infected outpatients (187 regular attenders,
      191 irregular attenders, and 66 nonattenders) identified from electronic medical
      records. Compared with the other attendance groups, nonattenders had higher viral
      loads, were less likely to be virologically suppressed, had lower CD4 counts, had
      higher depressive symptoms, life chaos, lower quality of life, and higher rates
      of food insecurity, and recent drug use. Additionally, nonattenders compared with
      regular attenders had lower physician relationship ratings, had lower medical
      information clarity and more often reported transportation as a barrier to clinic
      attendance. When viewed as a syndemic, compared with patients not reporting any
      barriers, patients with 3 or more individual-level barriers were more likely to
      have a detectable viral load (odds ratio = 3.60, 95% CI: 1.71 to 7.61). Our
      findings suggest that patients presenting to the clinic with multiple barriers
      should be prioritized for assistance and future interventions to improve
      retention in care. Interventions should address multiple individual and system
      level barriers simultaneously with particular attention to addressing depressive
      symptoms, organizational skills, relationship with the physician, and HIV-related
      health education. 

PMID- 25867781
TI  - "The more support you have the better": partner support and dyadic HIV care
      across the continuum for gay and bisexual men.
AB  - BACKGROUND: Gay, bisexual, and other men who have sex with men account for a
      disproportionate burden of HIV incidence in the United States, with one-third to
      two-thirds of these new HIV infections occurring within main partnerships. Early
      initiation and adherence to highly active antiretroviral treatment is a key
      factor in treating and preventing the transmission of HIV; however, the average
      rate of adherence in the United States is low. Social support has been examined
      as a source of improving health for people experiencing a variety of chronic
      health conditions. This study aims to understand perceptions of how dyadic HIV
      care could influence partner-specific support for same-sex male couples with a
      goal of improving adherence. METHODS: Data were collected from 5 focus group (n =
      35) discussions with gay and bisexual men in same-sex male relationships in
      Atlanta, GA. Participants discussed perceptions of how dyadic HIV care would
      impact partner support among serodiscordant and seroconcordant HIV-positive same
      sex male couples. Verbatim transcripts were segmented thematically and
      systematically analyzed to examine patterns. RESULTS: Participants described how
      dyadic HIV care can facilitate emotional, informational, and instrumental support
      at various stages across the continuum of care, depending on partner dynamics.
      Participants stated that dyadic HIV care can provide an additional "sense of
      togetherness" and "solidarity" that helps to "alleviate stress." CONCLUSIONS:
      Results suggest that dyadic approaches for HIV care across the continuum may be
      useful in promoting partner support and improving adherence. Future research
      should further examine dyadic interventions for HIV treatment among same-sex male
      couples.

PMID- 25867782
TI  - Benefits of a routine opt-out HIV testing and linkage to care program for
      previously diagnosed patients in publicly funded emergency departments in
      Houston, TX.
AB  - BACKGROUND: The Routine Universal Screening for HIV program provides opt-out HIV
      testing and linkage to care for emergency department (ED) patients in Harris
      Health System, Houston, TX. Seventy-five percent of patients testing positive in
      this program have been previously diagnosed. Whether linkage to care is increased
      among these patients is unknown. METHODS: We conducted a retrospective cohort
      study of persons tested for HIV in the ED between 2008 and 2012 but had a
      previously documented positive HIV test >=1 year prior. Outcomes were engagement
      in care (>=1 HIV outpatient visits in 6 months), retention in care (>=2 HIV
      outpatient visits in 12 months, at least 3 months apart), and virologic
      suppression (<200 copies/mL in 12 months) compared before and after the ED visit.
      Analysis was conducted using McNemar test and multivariate conditional logistic
      regression. RESULTS: A total of 202,767 HIV tests identified 2068 previously
      diagnosed patients. The mean age was 43 years with 65% male and 87% racial and
      ethnic minorities. Engagement in care increased from 41.3% previsit to 58.8%
      postvisit (P < 0.001). Retention in care increased from 32.6% previsit to 47.1%
      postvisit (P < 0.001). Virologic suppression increased from 22.8% previsit to
      34.0% postvisit (P < 0.001). Analyses revealed that engagement in care after
      visit improved most among younger participants (ages 16-24 years), retention
      improved across all groups, and virologic suppression improved most among
      participants aged 25-34 years. CONCLUSIONS: Routine opt-out HIV testing in an ED
      paired with standardized service linkage improves engagement, retention, and
      virologic suppression in previously diagnosed patients.

PMID- 25867783
TI  - Smartphone self-monitoring to support self-management among people living with
      HIV: perceived benefits and theory of change from a mixed-methods randomized
      pilot study.
AB  - BACKGROUND: Self-monitoring by mobile phone applications offers new opportunities
      to engage patients in self-management. Self-monitoring has not been examined
      thoroughly as a self-directed intervention strategy for self-management of
      multiple behaviors and states by people living with HIV (PLH). METHODS: PLH (n =
      50), primarily African American and Latino, were recruited from 2 AIDS services
      organizations and randomly assigned to daily smartphone (n = 34) or biweekly Web
      survey only (n = 16) self-monitoring for 6 weeks. Smartphone self-monitoring
      included responding to brief surveys on medication adherence, mental health,
      substance use, and sexual risk behaviors, and brief text diaries on stressful
      events. Qualitative analyses examine biweekly open-ended user-experience
      interviews regarding perceived benefits and barriers of self-monitoring, and to
      elaborate a theoretical model for potential efficacy of self-monitoring to
      support self-management for multiple domains. RESULTS: Self-monitoring functions
      include reflection for self-awareness, cues to action (reminders), reinforcements
      from self-tracking, and their potential effects on risk perceptions, motivations,
      skills, and behavioral activation states. Participants also reported therapeutic
      benefits related to self-expression for catharsis, nonjudgmental disclosure, and
      in-the-moment support. About one-third of participants reported that surveys were
      too long, frequent, or tedious. Some smartphone group participants suggested that
      daily self-monitoring was more beneficial than biweekly due to frequency and in
      the-moment availability. About twice as many daily self-monitoring group
      participants reported increased awareness and behavior change support from self
      monitoring compared with biweekly Web-survey only participants. CONCLUSIONS: Self
      monitoring is a potentially efficacious disruptive innovation for supporting self
      management by PLH and for complementing other interventions, but more research is
      needed to confirm efficacy, adoption, and sustainability.

PMID- 25867784
TI  - Reproducibility of Serum Potassium Values in Serum From Blood Samples Stored for
      Increasing Times Prior to Centrifugation and Analysis.
AB  - GOALS: The goal of this work was to determine if immediate versus postponed
      centrifugation of samples affects the levels of serum potassium. METHODS: Twenty
      participants donated normal venous blood that was collected in four serum
      separator tubes per donor, each of which was analyzed at 0, 1, 2, or 4 hr on the
      Siemens Advia 1800 autoanalyzer. RESULTS: Coefficients of variation (CVs) for
      potassium levels ranged from 0% to 7.6% with a mean of 3 +/- 2%. ANOVA testing of
      the means for all 20 samples showed a P-value of 0.72 (>0.05) indicating that
      there was no statistically significant difference between the means of the
      samples at the four time points. Sixteen samples were found to have CVs that were
      <=5%. Two samples showed increases of potassium from the reference range to
      levels higher than the upper reference limit, one of which had a 4-hr value that
      was within the reference or normal range (3.5-5 mEq/l). Overall, most samples
      were found to have reproducible levels of serum potassium. CONCLUSIONS: Serum
      potassium levels from stored whole blood collected in serum separator tubes are,
      for the most part, stable at room temperature for at least 4 hr prior to
      analysis. However, some samples can exhibit significant fluctuations of values.

PMID- 25867785
TI  - Effect of pH on floc properties and membrane fouling in coagulation -
      ultrafiltration process with ferric chloride and polyferric chloride.
AB  - Impact of pH on coagulation-ultrafiltration (C-UF) process was investigated with
      respect to coagulation efficiency, floc characteristics and membrane fouling in
      this study. Ferric chloride (FeCl3) and polyferric chloride with basicity of 1.0
      and 2.2 (denoted as PFC10 and PFC22) were used as coagulants and Fe (III) species
      in them was measured by a timed complexation spectroscopy method. Floc properties
      under four pH conditions were evaluated using a laser diffraction particle sizing
      device. Ultrafiltration experiments were conducted by a dead-end batch unit. The
      results showed that organic matter removal efficiency was higher under acidic
      conditions than under other pH conditions and turbidity removal efficiency was
      higher under alkaline condition. At same pH, FeCl3 containing higher monomeric
      and polymeric species (Fea and Feb) had better organic matter removal and higher
      turbidity removal efficiency was obtained by coagulants with larger percentage of
      polymer or colloidal species (Fec). Flocs formed under acidic ranges were larger,
      weaker and looser. At pH 4.0, 7.0 and 9.0, flocs by FeCl3 were larger and weaker
      than these by PFC10, followed by PFC22. In case of FeCl3 and PFC10, acidic pH
      conditions were helpful to reduce membrane fouling. For PFC22, permeate fluxes
      were less sensitive to pH variations.

PMID- 25867786
TI  - Nonsteroidal Anti-inflammatory Drug Use in a Patient With Hypertension: A
      Teachable Moment.

PMID- 25867787
TI  - Adrenal response of male rats exposed to prenatal stress and early postnatal
      stimulation.
AB  - Stress in pregnant rats caused by chronic immobilization alters the pattern of
      secretion of corticosterone and modifies the hypothalamic-pituitary-adrenal axis
      (HPA) of the fetus. Early postnatal handling, however, may reverse the effects of
      increased secretion of corticosterone. We investigated the effects of prenatal
      stress and postnatal handling on the activity of the HPA axis of male offspring
      of stressed female rats. Male 90-day-old rats from four groups were investigated:
      prenatally stressed animals without postnatal handling, prenatally stressed
      animals with postnatal handling, unstressed control animals with postnatal
      handling, and unstressed control animals without postnatal handling. After
      sacrifice, the adrenal glands were weighed to determine the adrenal-somatic
      index. Apoptosis was evaluated by TUNEL assay and active caspase-3 expression. We
      found that the adrenal gland cortex:medulla ratio increased in animals with
      prenatal stress and that eventually the stress caused apoptosis. Handling
      newborns to simulate maternal activity ameliorated some of the negative effects
      of prenatal stress. 

PMID- 25867788
TI  - Synthesis of bench-stable diarylmethylium tetrafluoroborates.
AB  - A representative number of bench-stable nonsymmetric diarylcarbenium
      tetrafluoroborates have been isolated via the direct coupling of aryl (or
      heteroaryl) aldehydes and N-heteroarenes and fully characterized. They have
      proven to be highly stable in the presence of both EDG and EWG substituents. An
      (E)-iminium vinylogous substructure has been shown as the common cation scaffold
      by X-ray analysis and by NOE determination. 

PMID- 25867789
TI  - Synthesis of Core-Shell Magnetic Fe3O4@poly(m-Phenylenediamine) Particles for
      Chromium Reduction and Adsorption.
AB  - Magnetic Fe3O4@poly(m-phenylenediamine) particles (Fe3O4@PmPDs) with well-defined
      core-shell structure were first designed for high performance Cr(VI) removal by
      taking advantages of the easy separation property of magnetic nanoparticles
      (MNPs) and the satisfactory adsorption property of polymers. Through controlling
      the polymerization on MNPs, directly coating was realized without the complicated
      premodification procedures. The particle property and adsorption mechanism were
      analyzed in details. Fe3O4@PmPDs exhibited tunable PmPD shell thickness from 10
      to 100 nm, high magnetic (~150 to ~73 emu g(-1)) and facile separation property
      by magnet. The coating of PmPD significantly enhanced Cr(VI) adsorption capacity
      from 46.79 (bare MNPs) to 246.09 mg g(-1) (71.55% PmPD loading proportion), much
      higher than many reported composite adsorbents. The high Cr(VI) removal
      performance was attributed to the adsorption of Cr(VI) on protonated imino groups
      and the efficient reduction of Cr(VI) to Cr(III) by amine, followed by Cr(III)
      chelated on imino groups, which are spontaneous and endothermic. The Fe3O4@PmPDs
      have great potential in treating Cr(VI)-contaminated water. 

PMID- 25867790
TI  - sigma-Insertive Mechanism versus Concerted Non-insertive Mechanism in the
      Intramolecular Hydroamination of Aminoalkenes Catalyzed by Phenoxyamine Magnesium
      Complexes: A Synthetic and Computational Study.
AB  - The phenoxyamine magnesium complexes [{ONN}MgCH2 Ph] (4 a: {ONN}=2,4-tBu2 -6-(CH2
      NMeCH2 CH2 NMe2 )C6 H2 O(-) ; 4 b: {ONN}=4-tBu-2-(CH2 NMeCH2 CH2 NMe2 )-6-(SiPh3
      )C6 H2 O(-) ) have been prepared and investigated with respect to their catalytic
      activity in the intramolecular hydroamination of aminoalkenes. The sterically
      more shielded triphenylsilyl-substituted complex 4 b exhibits better thermal
      stability and higher catalytic activity. Kinetic investigations using complex 4 b
      in the cyclisation of 1-allylcyclohexyl)methylamine (5 b), respectively, 2,2
      dimethylpent-4-en-1-amine (5 c), reveal a first-order rate dependence on
      substrate and catalyst concentration. A significant primary kinetic isotope
      effect of 3.9+/-0.2 in the cyclisation of 5 b suggests significant N-H bond
      disruption in the rate-determining transition state. The stoichiometric reaction
      of 4 b with 5 c revealed that at least two substrate molecules are required per
      magnesium centre to facilitate cyclisation. The reaction mechanism was further
      scrutinized computationally by examination of two rivalling mechanistic pathways.
      One scenario involves a coordinated amine molecule assisting in a concerted non
      insertive N-C ring closure with concurrent amino proton transfer from the amine
      onto the olefin, effectively combining the insertion and protonolysis step to a
      single step. The alternative mechanistic scenario involves a reversible olefin
      insertion step followed by rate-determining protonolysis. DFT reveals that a
      proton-assisted concerted N-C/C-H bond-forming pathway is energetically
      prohibitive in comparison to the kinetically less demanding sigma-insertive
      pathway (DeltaDeltaG(?) =5.6 kcal mol(-1) ). Thus, the sigma-insertive pathway is
      likely traversed exclusively. The DFT predicted total barrier of 23.1 kcal mol(
      1) (relative to the {ONN}Mg pyrrolide catalyst resting state) for magnesium-alkyl
      bond aminolysis matches the experimentally determined Eyring parameter (DeltaG(?)
      =24.1(+/-0.6) kcal mol(-1) (298 K)) gratifyingly well.

PMID- 25867791
TI  - Growth of modern branched columnar stromatolites in Lake Joyce, Antarctica.
AB  - Modern decimeter-scale columnar stromatolites from Lake Joyce, Antarctica, show a
      change in branching pattern during a period of lake level rise. Branching
      patterns correspond to a change in cyanobacterial community composition as
      preserved in authigenic calcite crystals. The transition in stromatolite
      morphology is preserved by mineralized layers that contain microfossils and
      cylindrical molds of cyanobacterial filaments. The molds are composed of two
      populations with different diameters. Large diameter molds (>2.8 MUm) are
      abundant in calcite forming the oldest stromatolite layers, but are absent from
      younger layers. In contrast, <2.3 MUm diameter molds are common in all
      stromatolites layers. Loss of large diameter molds corresponds to the transition
      from smooth-sided stromatolitic columns to branched and irregular columns. Mold
      diameters are similar to trichome diameters of the four most abundant living
      cyanobacteria morphotypes in Lake Joyce: Phormidium autumnale morphotypes have
      trichome diameters >3.5 MUm, whereas Leptolyngbya antarctica, L. fragilis, and
      Pseudanabaena frigida morphotypes have diameters <2.3 MUm. P. autumnale
      morphotypes were only common in mats at <12 m depth. Mats containing abundant P.
      autumnale morphotypes were smooth, whereas mats with few P. autumnale morphotypes
      contained small peaks and protruding bundles of filaments, suggesting that the
      absence of P. autumnale morphotypes allowed small-scale topography to develop on
      mats. Comparisons of living filaments and mold diameters suggest that P.
      autumnale morphotypes were present early in stromatolite growth, but disappeared
      from the community through time. We hypothesize that the mat-smoothing behavior
      of P. autumnale morphotypes inhibited nucleation of stromatolite branches. When
      P. autumnale morphotypes were excluded from the community, potentially reflecting
      a rise in lake level, short-wavelength roughness provided nuclei for stromatolite
      branches. This growth history provides a conceptual model for initiation of
      branched stromatolite growth resulting from a change in microbial community
      composition.

PMID- 25867792
TI  - Rapid Eye Movement Sleep Behavior Disorder and Neurodegenerative Disease.
AB  - IMPORTANCE: The dream enactment of rapid eye movement sleep behavior disorder
      (RBD) is often the first indication of an impending alpha-synuclein disorder,
      such as Parkinson disease, multiple-system atrophy, or dementia with Lewy bodies.
      OBJECTIVE: To provide an overview of RBD from the onset of dream enactment
      through the emergence of a parkinsonian disorder. EVIDENCE REVIEW: Peer-reviewed
      articles, including case reports, case series, retrospective reviews, prospective
      randomized trials, and basic science investigations, were identified in a PubMed
      search of articles on RBD from January 1, 1986, through July 31, 2014. FINDINGS:
      Under normal conditions, vivid dream mentation combined with skeletal muscle
      paralysis characterizes rapid eye movement sleep. In RBD, alpha-synuclein
      abnormalities in the brainstem disinhibit rapid eye movement sleep motor
      activity, leading to dream enactment. The behaviors of RBD are often theatrical,
      with complexity, aggression, and violence; fighting and fleeing actions can be
      injurious to patients as well as bed partners. Rapid eye movement sleep behavior
      disorder is distinguished from other parasomnias by clinical features and the
      demonstration of rapid eye movement sleep without atonia on polysomnography.
      Consistent with early neurodegeneration, patients with RBD demonstrate subtle
      motor, cognitive, and autonomic impairments. Approximately 50% of patients with
      spontaneous RBD will convert to a parkinsonian disorder within a decade.
      Ultimately, nearly all (81%-90%) patients with RBD develop a neurodegenerative
      disorder. Among patients with Parkinson disease, RBD predicts a non-tremor
      predominant subtype, gait freezing, and an aggressive clinical course. The most
      commonly cited RBD treatments include low-dose clonazepam or high-dose melatonin
      taken orally at bedtime. CONCLUSIONS AND RELEVANCE: Treatment of RBD can prevent
      injury to patients and bed partners. Because RBD is a prodromal syndrome of
      Parkinson disease (or related disorder), it represents a unique opportunity for
      developing and testing disease-modifying therapies.

PMID- 25867793
TI  - Hydrogen-bonding effects on infrared spectra from anharmonic computations: uracil
      water complexes and uracil dimers.
AB  - Hydrogen-bonding interactions lead to significant changes in the infrared (IR)
      spectrum, like frequency shifts of the order of magnitude of hundreds of cm(-1)
      and increases of IR intensity for bands related to vibrational modes of
      functional groups directly involved in the hydrogen-bonded bridges. We are
      actively developing a comprehensive and robust computational protocol aimed at
      the quantitative reproduction of the spectra of bio-organic and hybrid
      organic/inorganic molecular systems with a proper account of the variety of intra
      and intermolecular interactions. We have resorted to fully anharmonic quantum
      mechanical computations within the generalized second-order vibrational
      perturbation theory (GVPT2) approach, combined with the B3LYP-D3 method, in
      conjunction with basis sets of double-zeta plus polarization quality. Such an
      approach has been validated in a previous work ( Phys. Chem. Chem. Phys. 2014 ,
      16 , 10112 - 10128 ) for simulating the IR spectra of the monomers of nucleobases
      and some of their dimers. In the present contribution we have extended our
      computational protocol toward hybrid models, with the harmonic part computed at
      the B2PLYP level, in conjunction with the maug-cc-pVTZ basis set, or by a cost
      effective ONIOM B2PLYP:B3LYP focused model, where only part of the molecular
      system forming the hydrogen bonds is treated at the B2PLYP level of theory. In
      this work experimental frequencies available for a set of four uracil-water
      complexes have been considered as references for the computational methodologies
      applied to the simulation of hydrogen-bonding effects on the infrared spectrum,
      obtaining average uncertainties of about 22 cm(-1) for B3LYP-D3/N07D and improved
      description within 10 cm(-1) by hybrid B2PLYP/B3LYP-D3 approaches. The same
      computational schemes have been next applied to simulate fully anharmonic IR
      spectra of six different hydrogen-bonded uracil dimers, providing reliable
      support for future experimental investigations on hydrogen-bonded systems. 

PMID- 25867794
TI  - High-resolution proteome maps of Bacillus licheniformis cells growing in minimal
      medium.
AB  - Bacillus licheniformis is an important host for the industrial production of
      enzymes mainly because of its ability to secrete large amounts of protein. We
      analyzed the proteome of B. licheniformis cells growing in a minimal medium.
      Beside the cytosolic proteome, the membrane and the extracellular proteome were
      studied. We could identify 1470 proteins; 1168 proteins were classified as
      cytosolic proteins, 195 proteins with membrane-spanning domains were classified
      as membrane proteins, and 107 proteins, with either putative signals peptides or
      flagellin-like sequences, were classified as secreted proteins. The identified
      proteins were grouped into functional categories and used to reconstruct cellular
      functions and metabolic pathways of growing B. licheniformis cells. The largest
      group was proteins with functions in basic metabolic pathways such as carbon
      metabolism, amino acid and nucleotide synthesis and synthesis of fatty acids and
      cofactors. Many proteins detected were involved in DNA replication,
      transcription, and translation. Furthermore, a high number of proteins employed
      in the transport of a wide variety of compounds were found to be expressed in the
      cells. All MS data have been deposited in the ProteomeXchange with identifier
      PXD000791 (http://proteomecentral.proteomexchange.org/dataset/PXD000791). 

PMID- 25867795
TI  - Prevalence and correlates of neck injection among people who inject drugs in
      Tijuana, Mexico.
AB  - INTRODUCTION AND AIMS: Injecting drugs in the neck has been related to adverse
      health conditions such as jugular vein thrombosis, deep neck infections,
      aneurysm, haematomas, airway obstruction, vocal cord paralysis and wound
      botulism, among others. We identified prevalence and correlates of neck injection
      among people who inject drugs (PWID) in Tijuana, Mexico. DESIGN AND METHODS:
      Beginning in 2011, PWID aged >=18 years who injected drugs within the last month
      were recruited into a prospective cohort. At baseline and semi-annually, PWID
      completed interviewer-administered surveys soliciting data on drug-injecting
      practices. Logistic regression was used to identify predictors of injecting in
      the neck as the most frequent injection site at a single visit. RESULTS: Of 380
      PWID, 35.3% injected in the neck at least once in the past 6 months, among whom
      71.6% reported it as their most common injection site, the most common injecting
      site after the arms (47%). Controlling for age, years injecting and injecting
      frequency, injecting heroin and methamphetamine two or more times per day and
      having sought injection assistance were associated with injecting in the neck
      [adjusted odds ratios (AOR): 2.12; 95% confidence intervals (CI): 1.27-3.53 and
      AOR: 2.65; 95% CI: 1.52-4.53 respectively]. DISCUSSION AND CONCLUSIONS: Injecting
      in the neck was very common among PWID in Tijuana and was associated with
      polydrug use and seeking injection assistance. Tailoring harm reduction education
      interventions for individuals who provide injection assistance ('hit doctors')
      may allow for the dissemination of safe injecting knowledge to reduce injection
      related morbidity and mortality.

PMID- 25867796
TI  - Surface-induced changes in the conformation and glucan production of
      glucosyltransferase adsorbed on saliva-coated hydroxyapatite.
AB  - Glucosyltransferases (Gtfs) from S. mutans play critical roles in the development
      of virulent oral biofilms associated with dental caries disease. Gtfs adsorbed to
      the tooth surface produce glucans that promote local microbial colonization and
      provide an insoluble exopolysaccharides (EPS) matrix that facilitates biofilm
      initiation. Moreover, agents that inhibit the enzymatic activity of Gtfs in
      solution often have reduced or no effects on surface-adsorbed Gtfs. This study
      elucidated the mechanisms responsible for the differences in functionality that
      GtfB exhibits in solution vs surface-adsorbed. Upon adsorption to planar fused
      quartz substrates, GtfB displayed a 37% loss of helices and 36% increase of beta
      sheets, as determined by circular dichroism (CD) spectroscopy, and surface
      induced conformational changes were more severe on substrates modified with CH3-
      and NH2-terminated self-assembled monolayers. GtfB also underwent substantial
      conformation changes when adsorbing to hydroxyapatite (HA) microspheres, likely
      due to electrostatic interactions between negatively charged GtfB and positively
      charged HA crystal faces. Conformational changes were lessened when HA surfaces
      were coated with saliva (sHA) prior to GtfB adsorption. Furthermore, GtfB
      remained highly active on sHA, as determined by in situ attenuated total
      reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, producing glucans
      that were structurally different than GtfB in solution and known to increase the
      accumulation and virulence of biofilms. Our data provide the first insight into
      the structural underpinnings governing Gtf conformation and enzymatic function
      that occur on tooth surfaces in vivo, which may lead to designing potent new
      inhibitors and improved strategies to combat the formation of pathogenic oral
      biofilms. 

PMID- 25867797
TI  - Uncovering beat deafness: detecting rhythm disorders with synchronized finger
      tapping and perceptual timing tasks.
AB  - A set of behavioral tasks for assessing perceptual and sensorimotor timing
      abilities in the general population (i.e., non-musicians) is presented here with
      the goal of uncovering rhythm disorders, such as beat deafness. Beat deafness is
      characterized by poor performance in perceiving durations in auditory rhythmic
      patterns or poor synchronization of movement with auditory rhythms (e.g., with
      musical beats). These tasks include the synchronization of finger tapping to the
      beat of simple and complex auditory stimuli and the detection of rhythmic
      irregularities (anisochrony detection task) embedded in the same stimuli. These
      tests, which are easy to administer, include an assessment of both perceptual and
      sensorimotor timing abilities under different conditions (e.g., beat rates and
      types of auditory material) and are based on the same auditory stimuli, ranging
      from a simple metronome to a complex musical excerpt. The analysis of
      synchronized tapping data is performed with circular statistics, which provide
      reliable measures of synchronization accuracy (e.g., the difference between the
      timing of the taps and the timing of the pacing stimuli) and consistency.
      Circular statistics on tapping data are particularly well-suited for detecting
      individual differences in the general population. Synchronized tapping and
      anisochrony detection are sensitive measures for identifying profiles of rhythm
      disorders and have been used with success to uncover cases of poor
      synchronization with spared perceptual timing. This systematic assessment of
      perceptual and sensorimotor timing can be extended to populations of patients
      with brain damage, neurodegenerative diseases (e.g., Parkinson's disease), and
      developmental disorders (e.g., Attention Deficit Hyperactivity Disorder). 

PMID- 25867798
TI  - Hypophosphatemia is Associated with the Serial Administration of Triple-Dose
      Gadolinium to Patients for Brain MRI.
AB  - BACKGROUND AND PURPOSE: The purpose of this study is to report a metabolic
      abnormality associated with frequent, triple-dose Gadolinium (TdGd) use in MS
      patients during BECOME trial. METHODS: Potential clinical adverse events and lab
      abnormalities were monitored at each monthly MRI visit. Hypophosphatemia was
      defined as phosphate <2.5 mg/dL. Statistical analysis included McNemar's test for
      pairwise comparisons across visits and generalized estimating equations (GEE) to
      fit models over time. RESULTS: Eight hundred seventy seven phosphate values were
      analyzed from the first 12 months. Compared with 4% of subjects at screening, an
      average of 15.1% (95% confidence interval (CI): 11.4%-19.7%) of patients had
      hypophosphatemia at visits from months 1 to 12, during which subjects received
      serial TdGd. Forty four of seventy five (59%) patients developed hypophosphatemia
      at least once. We also found a significant increasing trend in hypophosphatemia
      by visit when treatment groups were evaluated together or separately (p < .001).
      There was a statistically significant decrease in frequency to 9.8% (95% CI: 4.6
      19.8%) by month 24 (p = .005) coinciding with a period of less frequent
      gadolinium administration. CONCLUSIONS: Serial TdGd in MS patients, unrelated to
      immunomodulatory treatment, was associated with increased frequency of
      hypophosphatemia that progressed with cumulative triple-dose and markedly
      decreased in second year, with less frequent triple-dose administration.

PMID- 25867799
TI  - Assessment of dendritic arborization in the dentate gyrus of the hippocampal
      region in mice.
AB  - Dendritic arborization has been shown to be a reliable marker for examination of
      structural and functional integrity of neurons. Indeed, the complexity and extent
      of dendritic arborization correlates well with the synaptic plasticity in these
      cells. A reliable method for assessment of dendritic arborization is needed to
      characterize the deleterious effects of neurological disorders on these
      structures and to determine the effects of therapeutic interventions. However,
      quantification of these structures has proven to be a formidable task given their
      complex and dynamic nature. Fortunately, sophisticated imaging techniques can be
      paired with conventional staining methods to assess the state of dendritic
      arborization, providing a more reliable and expeditious means of assessment.
      Below is an example of how these imaging techniques were paired with staining
      methods to characterize the dendritic arborization in wild type mice. These
      complementary imaging methods can be used to qualitatively and quantitatively
      assess dendritic arborization that span a rather wide area within the hippocampal
      region. 

PMID- 25867801
TI  - Crinophagy in Thyroid Follicular and Parafollicular Cells of Male Obese Zucker
      Rat.
AB  - Comparison between lean (Fa/?) and obese (fa/fa) young adult male Zucker rat
      thyroids reveals that obese rats display larger clusters of parafollicular cells
      than the lean ones with a lesser blood supply. Fa/? thyroid typically shows
      single or "twin" C cells in follicles; fa/fa parafollicular cells appear with
      three functional aspects. Crinophagy is found in the fa/fa C cells amassing
      numerous aberrant calcitonin-containing vesicles among which lysosomes build
      these autophagic bodies by capturing vesicle contents, other organelles and,
      fusing with each other, increase their size. Other C cells contain many secretory
      vesicles but show few or no crinophagic structures. Another parafollicular cell
      type is revealed with scant organelles and highly contrasted secretory vesicles,
      different from calcitonin. Hypercalcemia of fa/fa rats corresponds to increased C
      cells population with accrued calcitonin production but a low calcitonin plasma
      level - verified by others - is likely caused by crinophagy of the altered
      vesicles. In addition, the T thyrocytes of fa/fa rats exhibit crinophagy bodies;
      this can confirm their hypothyroidism. Possibly, the known leptin mutation along
      with other unknown paracrine secretions alter both T and C thyrocytes' functions
      of the fa/fa rats, allowing high intracellular calcium and lower pH favoring
      autophagocytosis. Other longitudinal, interdisciplinary studies should further
      clarify the complex paracrine interactions existing between these endocrine
      structures because this animal model could be useful to understand human defects,
      such as the metabolic syndrome that involves obesity, cardiovascular, renal,
      hepatic, non-insulin dependent diabetes mellitus (NIDDM), hypothyroidism defects,
      as well as the etiology of thyroid medullary tumors. 

PMID- 25867800
TI  - Low-income women's conceptualizations of food craving and food addiction.
AB  - Food craving and food addiction have been proposed as targets for obesity focused
      interventions. However, individuals' conceptualizations of these constructs are
      not well understood and no studies have employed a qualitative approach.
      Therefore, we sought to understand how women conceptualize food craving and food
      addiction. Low-income women with preschool-aged children (2-5years old)
      participated in either a semi-structured individual interview or focus group in
      which they were asked about their conceptualization of eating behaviors among
      adults and children. All responses were audio-recorded and transcribed. Themes
      were identified using the constant comparative method of qualitative analysis.
      Identified themes revealed that the women perceived food craving to be common,
      less severe and to a degree more humorous than food addiction. It was not felt
      that food cravings were something to be guarded against or resisted. Food
      addiction was described in a very "matter of fact" manner and was believed to be
      identifiable through its behavioral features including a compulsive need to have
      certain foods all the time. A more detailed understanding of how the general
      population perceives food craving and food addiction may enable more refined
      measurement of these constructs with questionnaire measures in the future. In
      addition, interventions may be designed to use the language most consistent with
      participants' conceptualizations of these constructs. 

PMID- 25867802
TI  - Wings as a new route of exposure to pesticides in the honey bee.
AB  - In pesticide risk assessment, estimating the routes and levels of exposure is
      critical. For honey bees subjected to pesticide spray, toxicity is assessed by
      thorax contact to account for all possible contact exposures. In the present
      study, the authors tested 6 active substances with different hydrophobicity. For
      the first time, the authors demonstrated that it is possible to induce mortality
      by pesticide contact with only the wings of the honey bee. The toxicities induced
      by contact with the wings and thorax were similar, with the wing median lethal
      dose (LD50) being 0.99 to 2.23 times higher than that of the thorax. This finding
      demonstrates that the wings represent a relevant route of exposure in the honey
      bee. In a second approach, the authors estimated the air volume displaced by the
      wings during 1 beating cycle to be 0.51 +/- 0.03 cm(3), which corresponds to a
      volume of 116.8 +/- 5.8 cm(3)  s(-1) at a wing beat frequency of 230 Hz. The
      authors then tested realistic scenarios of exposure for bees flying through a
      pesticide cloud at different concentrations. In the worst-case scenario, the dose
      accumulated during the flight reached 525 ng bee(-1)  s(-1). These results show
      that the procedure used to assess the risk posed by contact with pesticides could
      be improved by accounting for wing exposure.

PMID- 25867803
TI  - Two-dimensional photonic crystal chemical and biomolecular sensors.
AB  - We review recent progress in the development of two-dimensional (2-D) photonic
      crystal (PC) materials for chemical and biological sensing applications. Self
      assembly methods were developed in our laboratory to fabricate 2-D particle array
      monolayers on mercury and water surfaces. These hexagonal arrays strongly forward
      Bragg diffract light to report on their array spacings. By embedding these 2-D
      arrays onto responsive hydrogel surfaces, 2-D PC sensing materials can be
      fabricated. The 2-D PC sensors utilize responsive polymer hydrogels that are
      chemically functionalized to show volume phase transitions in selective response
      to particular chemical species. Novel hydrogels were also developed in our
      laboratory by cross-linking proteins while preserving their native structures to
      maintain their selective binding affinities. The volume phase transitions swell
      or shrink the hydrogels, which alter their 2-D array spacings, and shift their
      diffraction wavelengths. These shifts can be visually detected or spectrally
      measured. These 2-D PC sensing materials have been used for the detection of many
      analytes, such as pH, surfactants, metal ions, proteins, anionic drugs, and
      ammonia. We are exploring the use of organogels that use low vapor pressure ionic
      liquids as their mobile phases for sensing atmospheric analytes. 

PMID- 25867804
TI  - Effect of proteasome inhibitor 1 on wound healing: a potential scar prevention
      therapy.
AB  - In vitro and in vivo assessments suggest that proteasome inhibitors may be useful
      for modulating wound healing. METHODS: Proteasome Inhibitor I was used to assess
      the potential utility of proteasome inhibitors in improving wound healing in a
      standard rat model. Bilateral, 6 cm incisions were made 1 cm lateral to the spine
      of adult male Sprague Dawley rats. Animals were randomly assigned to 1 of 3
      groups: no treatment (n = 15), low concentration (1% w/v, n = 15), or high
      concentration (5% w/v, n = 15). Treatments were applied to the left side incision
      at 0 hours, 24 hours, and 48 hours. Right-side incisionsreceived a vehicle,
      dimethyl sulfoxide, alone and independent of the assigned group, serving as both
      external and internal controls. Rats were sacrificed at days 7, 14, and 28 (n = 5
      per group) and wounds subjected to mechanical testing and histology. RESULTS: No
      significant intergroup difference existed at 7 and 14 days. On day 28, a
      dosedependent increase in tensile strength with increasing Proteasome Inhibitor I
      was observed. CONCLUSION: Results suggest dimethyl sulfoxide was not the ideal
      vehicle and additional improvement may be realized by optimizing the delivery
      method.

PMID- 25867805
TI  - Pressure map technology for pressure ulcer patients: can we handle the truth?
AB  - Objective. The purpose of this study was to trial new pressure mapping
      technology for patients with pressure ulcers. METHODS: Pressure mapping data was
      recorded during 3 phases of technology implementation, as nurses became
      increasingly familiar with pressuremapping technology in a 55-bed, long-term
      acute care (LTAC) facility in North Texas. Forty-three patients with pressure
      ulcers were selected for the study. Patients with pressure ulcers, or who were
      considered at high risk for developing pressure ulcers based on a Braden score of
      <= 12, were selected to utilize a pressure-sensing device system. RESULTS:
      Turning timeliness improved greatly from the baseline phase to the last phase.
      The average turning after the 2-hour alarm decreased from 120 minutes to 44
      minutes, and the median time to turning decreased from 39 minutes to 17 minutes.
      If time past 2 hours is considered the most damaging time to tissue, these
      reductions (average and median) represented 63% and 56% less potential tissue
      damage. CONCLUSION: Pressure mapping technology is in its infancy and this paper
      discusses implications for the future, including barriers to implementation and
      potential advanced applications. While only changes in nursing practice were
      measured in this study, the changes observed suggest the technology can be
      instrumental in reducing hospital-acquired pressure ulcers and improving the
      healing of pressure wounds in the future.    .

PMID- 25867806
TI  - Treatment of sternal wound infection with vacuum-assisted closure.
AB  - INTRODUCTION: Previous work has demonstrated the efficacy of vacuum-assisted
      closure (VAC) in the treatment of poststernotomy local wound infections, compared
      to historical treatment protocol. The negative pressure has been found to protect
      wounds against contamination, prevent wound fluid retention, increase blood flow,
      and increase rates of granulation tissue formation. For this study, a
      retrospective analysis compared patients receiving VAC as definitive treatment
      versus bridging to delayed flap closure. METHODS: Sixteen patients developed
      sternal wound infections after cardiac surgeries at the authors' institution from
      2006 to 2008. Data was gathered regarding patient comorbidities, treatment
      method, and outcome. Study objectives included assessment of risk factors that
      warranted secondary surgicalclosure and examination of long-term followup where
      VAC was thedefinitive treatment modality. RESULTS: Group A (n = 12) had VAC as
      the final treatment modality. Group B (n = 4) required myocutaneous flap closure.
      One patient in Group B passed away prior to flap surgery. Both groups had similar
      risk factors, except Group B had a higher risk of body mass index (BMI) > 35 that
      was near statistically significant (P = 0.085; odds ratio = 0.0, 95% CI = [0.0 -
      1.21]). Group A required a shorter hospital stay on average. Long-term follow-up
      showed the majority of Group A had completely healed sternal wounds 2-3 years
      from initial cardiac surgery. CONCLUSIONS: Vacuum-assisted closure as definitive
      treatment modality is a successful, first line therapy for local superficial
      sternal wound infections. When deep infections occur, however, VAC as bridge-to
      flap coverage is recommended over attempted secondary healing with VAC.  .

PMID- 25867807
TI  - Use of modified superabsorbent polymer dressings for protease modulation in
      improved chronic wound care.
AB  - With more than 6 million patients affected with them in the United States,
      chronic ulcers represent one of the greatest problems in wound care. High levels
      of corrosive proteases, particularly matrix metalloproteinases (MMPs), within the
      wound environment are thoughtto contribute to the persistence of these wounds
      through denaturation of connective tissue proteins crucial to healing
      progression. Therefore, there is considerable interest in protease modulation
      using wound dressings to promote healing in chronic wounds. Such modulation could
      be achieved by direct absorption of proteases, by depleting co- factors within
      the wound, or by release of protease inhibitors. METHOD: The aim of this study is
      to examine protease modulation of a range of dressings with different
      chemistries, particularly those having demonstrated efficacy in chronic wound
      healing. RESULTS: XTRASORB(r) HCS (dressing A) and XTRASORB(r) Foam (dressing B)
      were able to modulate proteases by both direct absorption of MMPs and depleting
      metal ion co-factors, and resulted in complete elimination of protease activity
      in the assay used. Duoderm(r) (dressing C) was able to modulate proteases by
      direct absorption only, and not by co-factor depletion. Promogran(r) (dressing D)
      was able to reduce MMP activity, but this was shown to be pH dependant, with any
      protease modulation being lost at neutral pH. Neither Allevyn(r) (dressing E) nor
      Vigilon(r) (dressing F) were able to modulate proteases by any mechanism. None of
      the protease modulating dressings acted through the release of protease
      inhibitors. CONCLUSION: Of the dressings studied, dressing A and dressing B were
      the most effective protease modulators due to their acting through 2 separate
      mechanisms.    .

PMID- 25867808
TI  - A Patient With a Thyrotropin-Secreting Microadenoma and Resistance to Thyroid
      Hormone (P453T).
AB  - CONTEXT: Resistance to thyroid hormone (RTH) beta is due to mutations in the beta
      isoform of the thyroid hormone receptor (TR). TSH-secreting adenomas (TSHomas)
      are presumed to represent clonal expansion and have been reported to contain
      TRbeta gene mutations. Mice with a knock-in mutation in the TRbeta gene
      spontaneously develop TSHomas, although as yet no patient has been reported to
      have both a TSHoma and RTHbeta. OBJECTIVE: We investigated a 12-year-old girl
      with elevated serum T4 concentration, inappropriately high TSH levels, and a
      pituitary adenoma. DESIGN AND INTERVENTION: Clinical, biochemical, and
      radiological assessments were performed at baseline and after a transsphenoidal
      pituitary adenomectomy. RESULTS: The patient's laboratory results included: TSH,
      21.12 mIU/L (0.35-4.94 mIU/L); free T3, 14.25 pmol/L (2.63-5.7 pmol/L); free T4,
      28.79 pmol/L (9.01-19.05 pmol/L); serum glycoprotein hormone alpha-subunit (alpha
      GSU), 0.32 ng/ml (0.22-0.39 ng/ml); and alpha-GSU/TSH, 0.15. Thyroid radioiodine
      uptake was increased by 94.4% at 24 hours. A T3 suppression test showed
      incomplete suppression of the serum TSH concentration and blunted response of the
      peripheral thyroid hormone markers. The sequence of TRbeta exons confirmed a
      P453T mutation in the TRbeta gene. Pituitary magnetic resonance imaging revealed
      a microadenoma in the left side of the pituitary. The patient underwent
      transsphenoidal pituitary adenomectomy. Histologically, the tumor stained
      positively for TSH-beta, human Chorionic Gonadotropin alpha (HCG-alpha), GH,
      prolactin, and ACTH. After removal of the tumor, the patient's thyroid function
      improved significantly, and she experienced the onset of menarche and an increase
      in linear growth as well. CONCLUSIONS: This patient with RTHbeta had a TSHoma
      consistent with previous findings linking somatic TRbeta mutations to TSHomas.

PMID- 25867809
TI  - High Diagnostic Accuracy Based on CLDN10, HMGA2, and LAMB3 Transcripts in
      Papillary Thyroid Carcinoma.
AB  - CONTEXT: Thyroid nodules are common in adult population and papillary thyroid
      carcinoma (PTC) is the most frequent malignant finding. The natural history of
      PTC remains poorly understood and current diagnostic methods limitations are
      responsible for a significant number of potentially avoidable surgeries.
      OBJECTIVE: This study aimed to identify molecular markers to improve the
      diagnosis of thyroid lesions. DESIGN: Gene expression profiling was performed
      using microarray in 61 PTC and 13 surrounding normal tissues (NT). A reliable
      gene list was established using cross-study validation (138 matched PTC/NT from
      external databases). Results were collectively interpreted by in silico analysis.
      A panel of 28 transcripts was evaluated by RT-qPCR, including benign thyroid
      lesions (BTL) and other follicular cell-derived thyroid carcinomas (OFDTC). A
      diagnostic algorithm was developed (training set: 23 NT, 8 BTL, and 86 PTC),
      validated (independent set: 10 NT, 140 BTL, 120 PTC, and 12 OFDTC) and associated
      with clinical features. RESULTS: GABRB2 was ranked as the most frequently up
      regulated gene in PTC (cross-study validation). Altered genes in PTC suggested a
      loss of T4 responsiveness and dysregulation of retinoic acid metabolism,
      highlighting the putative activation of EZH2 and histone deacetylases (predicted
      in silico). An algorithm combining CLDN10, HMGA2, and LAMB3 transcripts was able
      to discriminate tumors from BTL samples (94% sensitivity and 96% specificity in
      validation set). High algorithm scores were associated with regional lymph node
      metastases. CONCLUSIONS: A promising tool with high performance for PTC diagnosis
      based on three transcripts was designed with the potential to predict lymph node
      metastasis risk.

PMID- 25867811
TI  - Longitudinal Relationships between Reproductive Hormones and Cognitive Decline in
      Older Men: The Concord Health and Ageing in Men Project.
AB  - CONTEXT: The longitudinal relationship between declining levels of reproductive
      hormones and cognitive function remains unclear in older men. OBJECTIVES: The
      objective of this study was to examine the temporal relationship between changes
      in major reproductive hormone levels and cognitive decline over time. DESIGN,
      SETTING, AND PARTICIPANTS: Men age 70 years and older from the Concord Health and
      Ageing in Men Project (CHAMP) were assessed at baseline (2005-2007; n = 1705), 2
      year followup (2007-2009; n = 1367), and 5-year followup (2010-2013; n = 958).
      MAIN OUTCOMES AND MEASURES: At all assessments, T, dihydrotestosterone (DHT),
      estradiol (E2), and estrone (E1) were measured by liquid chromatography-tandem
      mass spectrometry, and SHBG, LH, and FSH by immunoassay. Dementia was diagnosed
      at baseline by clinical assessment and review by a specialist panel. Cognitive
      function was measured at all three assessments by the Mini Mental State
      Examination. RESULTS: None of the baseline reproductive hormones predicted
      cognitive decline in men without dementia over 5 years. However, the change in
      serum hormones over time was associated with cognitive decline. In univariate
      analysis, change in all the studied hormones, except for E2, was significantly
      associated with cognitive decline. However, in multivariate-adjusted models
      accounting for potential confounders, only change in serum T (beta = 0.067), DHT
      (beta = 0.394), calculated free T (beta = 0.005), and E1 (beta = 0.009) remained
      significantly associated (P < .05) with cognitive decline. Men who had dementia
      at baseline had significantly greater decline in serum T levels, but not in other
      studied hormones, over the 5 years. CONCLUSIONS: Our findings show that decline
      in androgen status is associated with cognitive decline in older men, but the
      causality of this association requires further elucidation.

PMID- 25867810
TI  - Association between Inflammation and Biological Variation in Hemoglobin A1c in
      U.S. Nondiabetic Adults.
AB  - CONTEXT: Inflammation is associated with higher glycated hemoglobin (HbA1c)
      levels. Whether the relationship is independent of blood glucose concentration
      remains unclear. OBJECTIVE: The hemoglobin glycation index (HGI) was used to test
      the hypothesis that interindividual variation in HbA1c is associated with
      inflammation. PARTICIPANTS: This study used nondiabetic adults from the National
      Health and Nutrition Examination Survey (1999-2008). MAIN OUTCOME MEASURES: A
      subsample of participants was used to estimate the linear regression relationship
      between HbA1c and fasting plasma glucose (FPG). Predicted HbA1c were calculated
      for 7323 nondiabetic participants by inserting FPG into the equation, HbA1c =
      0.017 * FPG (mg/dL) + 3.7. HGI was calculated as the difference between the
      observed and predicted HbA1c and the population was divided into low, moderate,
      and high HGI subgroups. Polymorphonuclear leukocytes (PMNL), monocytes, and C
      reactive protein (CRP) were used as biomarkers of inflammation. RESULTS: Mean
      HbA1c, CRP, monocyte, and PMNL levels, but not FPG, progressively increased in
      the low, moderate, and high HGI subgroups. There were disproportionately more
      Blacks than whites in the high HGI subgroup. CRP (beta, 0.009; 95% confidence
      interval [CI], 0.0001-0.017), PMNL (beta, 0.036; 95% CI, 0.010-0.062), and
      monocyte count (beta, 0.072; 95% CI, 0.041-0.104) were each independent
      predictors of HGI after adjustment for age, sex, race, triglycerides, hemoglobin
      level, mean corpuscular volume, red cell distribution width, and obesity status.
      CONCLUSIONS: HGI reflects the effects of inflammation on HbA1c in a nondiabetic
      population of U.S. adults and may be a marker of risk associated with
      inflammation independent of FPG, race, and obesity.

PMID- 25867812
TI  - Thiamazole Pretreatment Lowers the (131)I Activity Needed to Cure Hyperthyroidism
      in Patients With Nodular Goiter.
AB  - CONTEXT: Relatively low radioiodine uptake (RAIU) represents a common obstacle
      for radioiodine ((131)I) therapy in patients with multinodular goiter complicated
      by hyperthyroidism. OBJECTIVE: To evaluate whether thiamazole (MTZ) pretreatment
      can increase (131)I therapeutic efficacy. DESIGN AND SETTING: Twenty-two patients
      with multinodular goiter, subclinical hyperthyroidism, and RAIU < 50% were
      randomized to receive either a low-iodine diet (LID; n = 10) or MTZ 30 mg/d (n =
      12) for 42 days. Thyroid function and 24-hour RAIU were measured before and after
      treatment. Thyroid volume was evaluated by either magnetic resonance imaging or
      single photon emission computed tomography. RESULTS: Mean 24-hour RAIU increased
      significantly from 32 +/- 10% to 63 +/- 18% in the MTZ group (P < .001).
      Consequently, there was a 31% decrease in the calculated median therapeutic
      (131)I activity after MTZ (P < .05). No significant changes in 24-hour RAIU were
      observed after diet. In the MTZ group, median serum TSH levels increased
      significantly by 9% and mean serum free T4 and free T3 concentrations decreased
      by 22% and 15%, respectively, whereas no changes in thyroid function were
      observed in the LID group. Thyroid volume did not significantly change in either
      of the two groups. At 12 months after radioiodine treatment, median serum TSH was
      within the normal range in both groups. CONCLUSIONS: MTZ treatment before (131)I
      therapy resulted in an average 2-fold increase in thyroid RAIU and enhanced the
      efficiency of radioiodine therapy assessed at 12 months. MTZ pretreatment is
      therefore a safe, easily accessible alternative to recombinant human TSH
      stimulation and a more effective option than LID.

PMID- 25867813
TI  - Additive Genetic Effects on Circulating Periostin Contribute to the Heritability
      of Bone Microstructure.
AB  - CONTEXT: Genetic factors account for 60-80% of the areal bone mineral density
      (aBMD) variance, whereas the heritability of bone microstructure is not clearly
      established. aBMD and microstructure are under the control of osteocytes, which
      regulate bone formation through the expression of molecules such as sclerostin
      (SOST) and periostin (POSTN). OBJECTIVE: We hypothesized that additive genetic
      effects contribute to serum levels of SOST and POSTN and thereby to the
      individual variance of bone microstructure. SUBJECTS AND METHODS: In a
      retrospective analysis of 432 subjects from the Geneva Retiree Cohort age 64.9 +/
      1.4 years and 96 of their offspring age 37.9 +/- 5.7 years, we measured serum
      SOST (sSOST) and serum POSTN (sPOSTN), distal radius and tibia microstructure,
      hip and lumbar spine aBMD, and bone turnover markers, Heritability (h(2), %) was
      calculated as twice the slope of the regression (beta) between parents and
      offspring. RESULTS: cPOSTN levels were significantly higher in men than women and
      in offspring than parents. h(2) values for bone microstructural traits ranged
      from 22-64% depending on the envelope (trabecular [Tb] or cortical [Ct]) and
      skeletal site (radius or tibia), whereas h(2) for sPOSTN and sSOST was 50% and
      40%, respectively. sPOSTN was positively associated with Tb bone volume on total
      volume and Ct thickness, and negatively with Ct porosity. The associations for Ct
      parameters remain significant after adjustment for propetide of type-I
      procollagen, cross-linked telopeptide of type I collagen, femoral neck aBMD, sex
      or age. After adjustment of bone traits for sPOSTN, h(2) values decreased for
      several Tb and Ct bone parameters, but not for aBMD. In contrast, adjusting for
      sSOST did not alter h(2) values for bone traits. CONCLUSIONS: Additive genetic
      effects account for a substantial proportion of the individual variance of bone
      microstructure, sPOSTN, and sSOST. sPOSTN is largely inherited as a sex-related
      trait and carries an important contribution to the heritability of bone
      microstructure, indicating that these traits are at least partly determined by
      common genetic effects.

PMID- 25867814
TI  - Moderate Exercise Increases Affinity of Large Very Low-Density Lipoproteins for
      Hydrolysis by Lipoprotein Lipase.
AB  - CONTEXT: Postprandial triglyceride (TG) concentration is independently associated
      with cardiovascular disease risk. Exercise reduces postprandial TG
      concentrations, but the mechanisms responsible are unclear. OBJECTIVE: The
      objective was to determine the effects of exercise on affinity of chylomicrons,
      large very low-density lipoproteins (VLDL1), and smaller VLDL (VLDL2) for
      lipoprotein lipase (LPL)-mediated TG hydrolysis. DESIGN: This was designed as a
      within-participant crossover study. SETTING: The setting was a university
      metabolic investigation unit. PARTICIPANTS: Participants were 10 overweight/obese
      men. INTERVENTIONS: Participants undertook two oral fat tolerance tests,
      separated by 7-14 days, in which they had blood taken while fasting and for 4
      hours after a high-fat mixed meal. On the afternoon before one test, they
      performed a 90-minute treadmill walk at 50% maximal oxygen uptake (exercise trial
      [EX]); no exercise was performed before the control trial (CON). MAIN OUTCOME
      MEASURES: We measured circulating TG-rich lipoprotein concentrations and affinity
      of chylomicrons, VLDL1, and VLDL2 for LPL-mediated TG hydrolysis. RESULTS:
      Exercise significantly reduced fasting VLDL1-TG concentration (CON, 0.49 [0.33
      0.72] mmol.L(-1); EX, 0.36 [0.22-0.59] mmol.L(-1); geometric means [95%
      confidence interval]; P = .04). Time-averaged postprandial chylomicron-TG (CON,
      0.55 +/- 0.10 mmol.L(-1); EX, 0.39 +/- 0.08 mmol.L(-1); mean +/- SEM; P = .03)
      and VLDL1-TG (CON, 0.85 +/- 0.13 mmol.L(-1); EX, 0.66 +/- 0.10 mmol.L(-1); P =
      .01) concentrations were both lower in EX than CON. Affinity of VLDL1 for LPL
      mediated TG hydrolysis increased by 2.2 (1.3-3.7)-fold [geometric mean (95%
      confidence interval)] (P = .02) in the fasted state and 2.6 (1.8-2.6)-fold (P =
      .001) postprandially. Affinity of chylomicrons and VLDL2 was not significantly
      different between trials. CONCLUSIONS: Exercise increases affinity of VLDL1 for
      LPL-mediated TG hydrolysis both fasting and postprandially. This mechanism is
      likely to contribute to the TG-lowering effect of exercise.

PMID- 25867815
TI  - Abnormal Skeletal Strength and Microarchitecture in Women With Celiac Disease.
AB  - CONTEXT: Osteoporosis is often a presenting sign of celiac disease (CD). Whether
      skeletal fragility in CD is associated with microarchitectural abnormalities is
      not known. OBJECTIVE: The objective of the study was to evaluate
      microarchitecture and biomechanical properties of bone in CD. DESIGN: This was a
      case-control study. SETTING: The study was conducted at a university hospital
      outpatient facility. PATIENTS: Patients included premenopausal women with newly
      diagnosed CD (n = 33) and healthy controls (n = 33). MAIN OUTCOME MEASURES: Areal
      bone mineral density by dual-energy x-ray absorptiometry was measured as was
      trabecular and cortical volumetric bone mineral density (vBMD) and
      microarchitecture by high-resolution peripheral computed tomography of the distal
      radius and tibia. Whole-bone stiffness estimated by finite element analysis. PTH,
      25-hydroxyvitamin D, and bone turnover markers were also measured. RESULTS:
      Groups had similar age, race, and body mass index. Both groups had sufficient 25
      hydroxyvitamin D and normal calcium and PTH. Areal bone mineral density was lower
      in CD. By high-resolution peripheral computed tomography, CD had lower trabecular
      vBMD, fewer, more widely, and irregularly spaced trabeculae at both the radius
      and tibia (8%-33%). At the tibia, they also had lower total density (8%) and
      thinner cortices (10%). Whole-bone stiffness and failure load were lower (11%
      21%) in CD at both sites. Biomechanical deficits were associated with trabecular
      abnormalities. CONCLUSIONS: Women with CD had abnormal vBMD and microarchitecture
      at both the radius and tibia. Trabecular bone was preferentially affected. These
      deficits were associated with lower estimates of skeletal strength. These
      findings suggest a potential structural mechanism for skeletal fragility in CD
      and support further research into the pathogenesis of fracture in this
      population.

PMID- 25867816
TI  - Chlorhexidine treatment for the prevention of dental caries in children and
      adolescents.
AB  - BACKGROUND: Dental caries (tooth decay) is a common disease that is preventable
      by reducing the dietary intake of free sugars and using topical sodium fluoride
      products. An antibacterial agent known as chlorhexidine may also help prevent
      caries. A number of over-the-counter and professionally administered
      chlorhexidine-based preparations are available in a variety of formulations and
      in a range of strengths. Although previous reviews have concluded that some
      formulations of chlorhexidine may be effective in inhibiting the progression of
      established caries in children, there is currently a lack of evidence to either
      claim or refute a benefit for its use in preventing dental caries. OBJECTIVES: To
      assess the effects of chlorhexidine-containing oral products (toothpastes,
      mouthrinses, varnishes, gels, gums and sprays) on the prevention of dental caries
      in children and adolescents. SEARCH METHODS: We searched the Cochrane Oral Health
      Group Trials Register (25 February 2015), the Cochrane Central Register of
      Controlled Trials (CENTRAL; 2014, Issue 12), MEDLINE via OVID (1946 to 25
      February 2015), EMBASE via OVID (1980 to 25 February 2015) and CINAHL via EBSCO
      (1937 to 25 February 2015). We handsearched several journals placed no language
      restrictions on our search. After duplicate citations were removed, the
      electronic searches retrieved 1075 references to studies. SELECTION CRITERIA: We
      included parallel-group, randomised controlled trials (RCTs) that compared the
      caries preventive effects of chlorhexidine gels, toothpastes, varnishes,
      mouthrinses, chewing gums or sprays with each other, placebo or no intervention
      in children and adolescents. We excluded trials with combined interventions of
      chlorhexidine and fluoride or comparisons between chlorhexidine and fluoride
      interventions. DATA COLLECTION AND ANALYSIS: Two review authors independently
      extracted trial data and assessed risk of bias. We resolved disagreements by
      consensus. We contacted trial authors for clarification or additional study
      details when necessary. The number of included studies that were suitable for
      meta-analysis was limited due to the clinical diversity of the included studies
      with respect to age, composition of intervention, and variation in outcome
      measures and follow-up. Where we were unable to conduct meta-analysis, we elected
      to present a narrative synthesis of the results. MAIN RESULTS: We included eight
      RCTs that evaluated the effects of chlorhexidine varnishes (1%, 10% or 40%
      concentration) and chlorhexidine gel (0.12%) on the primary or permanent teeth,
      or both, of children from birth to 15 years of age at the start of the study. The
      studies randomised a total of 2876 participants, of whom 2276 (79%) were
      evaluated. We assessed six studies as being at high risk of bias overall and two
      studies as being at unclear risk of bias overall. Follow-up assessment ranged
      from 6 to 36 months.Six trials compared chlorhexidine varnish with placebo or no
      treatment. It was possible to pool the data from two trials in the permanent
      dentition (one study using 10% chlorhexidine and the other, 40%). This led to an
      increase in the DMFS increment in the varnish group of 0.53 (95% confidence
      interval (CI) -0.47 to 1.53; two trials, 690 participants; very low quality
      evidence). Only one trial (10% concentration chlorhexidine varnish) provided
      usable data for elevated mutans streptococci levels > 4 with RR 0.93 (95% CI 0.80
      to 1.07, 496 participants; very low quality evidence). One trial measured adverse
      effects (for example, ulcers or tooth staining) and reported that there were
      none; another trial reported that no side effects of the treatment were noted. No
      trials reported on pain, quality of life, patient satisfaction or costs.Two
      trials compared chlorhexidine gel (0.12% concentration) with no treatment in the
      primary dentition. The presence of new caries gave rise to a 95% confidence
      interval that was compatible with either an increase or a decrease in caries
      incidence (RR 1.00, 95% CI 0.36 to 2.77; 487 participants; very low quality
      evidence). Similarly, data for the effects of chlorhexidine gel on the prevalence
      of mutans streptococci were inconclusive (RR 1.26, 95% CI 0.95 to 1.66; two
      trials, 490 participants; very low quality evidence). Both trials measured
      adverse effects and did not observe any. Neither of these trials reported on the
      other secondary outcomes such as measures of pain, quality of life, patient
      satisfaction or direct and indirect costs of interventions. AUTHORS' CONCLUSIONS:
      We found little evidence from the eight trials on varnishes and gels included in
      this review to either support or refute the assertion that chlorhexidine is more
      effective than placebo or no treatment in the prevention of caries or the
      reduction of mutans streptococci levels in children and adolescents. There were
      no trials on other products containing chlorhexidine such as sprays, toothpastes,
      chewing gums or mouthrinses. Further high quality research is required, in
      particular evaluating the effects on both the primary and permanent dentition and
      using other chlorhexidine-containing oral products.

PMID- 25867817
TI  - iPSC-MSCs Combined with Low-Dose Rapamycin Induced Islet Allograft Tolerance
      Through Suppressing Th1 and Enhancing Regulatory T-Cell Differentiation.
AB  - Mesenchymal stem cell (MSC) differentiation is dramatically reduced after long
      term in vitro culture, which limits their application. MSCs derived from induced
      pluripotent stem cells (iPSCs-MSCs) represent a novel source of MSCs. In this
      study, we investigated the therapeutic effect of iPSC-MSCs on diabetic mice.
      Streptozocin-induced diabetic mice transplanted with 400 islets alone or with
      1*10(6) iPSC-MSCs were examined following rapamycin injection (0.1 mg/kg/day,
      i.p., from days 0 to 9) after transplantation. Our results showed that iPSC-MSCs
      combined with rapamycin significantly prolonged islet allograft survival in the
      diabetic mice; 50% of recipients exhibited long-term survival (>100 days).
      Histopathological analysis revealed that iPSC-MSCs combined with rapamycin
      preserved the graft effectively, inhibited inflammatory cell infiltration, and
      resulted in substantial release of insulin. Flow cytometry results showed that
      the proportion of CD4(+) and CD8(+) T cells was significantly reduced, and the
      number of T regulatory cells increased in the spleen and lymph nodes in the iPSC
      MSCs combined with the rapamycin group compared with the rapamycin-alone group.
      Production of the Th1 proinflammatory cytokines interleukin-2 (IL-2) and
      interferon-gamma was reduced, and secretion of the anti-inflammatory cytokines IL
      10 and transforming growth factor-beta was enhanced compared with the rapamycin
      group, as determined using enzyme-linked immunosorbent assays. Transwell
      separation significantly weakened the immunosuppressive effects of iPSC-MSCs on
      the proliferation of Con A-treated splenic T cells, which indicated that the
      combined treatment exerted immunosuppressive effects through cell-cell contact
      and regulation of cytokine production. Taken together, these findings highlight
      the potential application of iPSC-MSCs in islet transplantation. 

PMID- 25867818
TI  - Total Synthesis of Gelsemoxonine through a Spirocyclopropane Isoxazolidine Ring
      Contraction.
AB  - Plants of the species Gelsemium have found application in traditional Asian
      medicine for over a thousand years. Gelsemoxonine represents a novel constituent
      of this plant incorporating a highly functionalized azetidine at its core. We
      herein report a full account of our studies directed toward the total synthesis
      of gelsemoxonine that relies on a conceptually new approach for the construction
      of the central azacyclobutane. A spirocyclopropane isoxazolidine ring contraction
      was employed to access a key beta-lactam intermediate, which could be further
      elaborated to the azetidine of the natural product. In the course of our studies,
      we have gained detailed insight into this intriguing transformation. Furthermore,
      we report on previously unnoticed oligomerization chemistry of gelsemoxonine. We
      also document an enantioselective synthesis of a key precursor en route to
      gelsemoxonine. 

PMID- 25867819
TI  - Transplantation Effectiveness of Induced Pluripotent Stem Cells Is Improved by a
      Fibrinogen Biomatrix in an Experimental Model of Ischemic Heart Failure.
AB  - OBJECTIVES: The aim of this study was to investigate whether a fibrinogen
      biomatrix improves the transplantation effectiveness of induced pluripotent stem
      cells (iPSCs) in a model of myocardial infarction. BACKGROUND: Early retention,
      engraftment, and cell proliferation are important factors for successful cardiac
      stem cell therapy. Common transplantation techniques involve the direction
      injection of cells in aqueous media. However, this approach yields low retention
      and variable cell biodistribution, leading to reduced grafts that are unable to
      sufficiently regenerate damaged myocardium. Biologically compatible scaffolds
      that improve the retention of injected cells can improve cardiac stem cell
      therapy. METHODS: Murine iPSCs were transfected for luciferase reporter gene
      expression. First, in vitro experiments were performed comparing cell viability
      in fibrinogen and medium. Second, iPSCs were transplanted intramyocardially by
      direct injection into ischemic myocardium of immunodeficient mice, following
      permanent left coronary artery ligation. Cells were delivered in medium or
      fibrinogen. Follow-up included graft assessment by bioluminescence imaging, the
      evaluation of cardiac function by magnetic resonance imaging, and histology to
      evaluate graft size and determine the extent of myocardial scarring. RESULTS: In
      vitro experiments showed proliferation of iPSCs in fibrinogen from 6.4*10(3)+/
      8.0*10(2) after 24 h to 2.1*10(4)+/-3.2*10(3) after 72 h. Early cardiac cell
      amount in control group animals was low (23.7%+/-0.7%) with massive cell
      accumulation in the right (46.3%+/-1.0%) and the left lung (30.0%+/-0.6%). When
      iPSCs were injected applying the fibrinogen biomatrix, intramyocardial cell
      amount was increased (66.3%+/-0.9%) with demonstrable graft proliferation over
      the experimental time course. Left ventricle-function was higher in the
      fibrinogen group (42.9%+/-2.8%), also showing a higher fraction of refilled
      infarcted-area (66.9%+/-2.7%). CONCLUSIONS: The fibrinogen biomatrix improved
      cardiac iPSc retention, sustaining functional improvement and cellular refill of
      infarcted myocardium. Therefore, fibrinogen can be considered an ideal biological
      scaffold for intramyocardial stem cell transplantations.

PMID- 25867820
TI  - Intrauterine telemetry to measure mouse contractile pressure in vivo.
AB  - A complex integration of molecular and electrical signals is needed to transform
      a quiescent uterus into a contractile organ at the end of pregnancy. Despite the
      discovery of key regulators of uterine contractility, this process is still not
      fully understood. Transgenic mice provide an ideal model in which to study
      parturition. Previously, the only method to study uterine contractility in the
      mouse was ex vivo isometric tension recordings, which are suboptimal for several
      reasons. The uterus must be removed from its physiological environment, a limited
      time course of investigation is possible, and the mice must be sacrificed. The
      recent development of radiometric telemetry has allowed for longitudinal, real
      time measurements of in vivo intrauterine pressure in mice. Here, the
      implantation of an intrauterine telemeter to measure pressure changes in the
      mouse uterus from mid-pregnancy until delivery is described. By comparing
      differences in pressures between wild type and transgenic mice, the physiological
      impact of a gene of interest can be elucidated. This technique should expedite
      the development of therapeutics used to treat myometrial disorders during
      pregnancy, including preterm labor. 

PMID- 25867821
TI  - Single-walled carbon nanotube/metalloporphyrin composites for the chemiresistive
      detection of amines and meat spoilage.
AB  - Chemiresistive detectors for amine vapors were made from single-walled carbon
      nanotubes by noncovalent modification with cobalt meso-arylporphyrin complexes.
      We show that through changes in the oxidation state of the metal, the electron
      withdrawing character of the porphyrinato ligand, and the counteranion, the
      magnitude of the chemiresistive response to ammonia could be improved. The
      devices exhibited sub-ppm sensitivity and high selectivity toward amines as well
      as good stability to air, moisture, and time. The application of these
      chemiresistors in the detection of various biogenic amines (i.e. putrescine,
      cadaverine) and in the monitoring of spoilage in raw meat and fish samples
      (chicken, pork, salmon, cod) over several days was also demonstrated. 

PMID- 25867822
TI  - A trinuclear oxo-chromium(III) complex containing the natural flavonoid
      primuletin: synthesis, characterization, and antiradical properties.
AB  - A new trinuclear oxo-centered chromium(III) complex with formula
      [Cr3O(CH3CO2)6(L)(H2O)2] (L = 5-hydroxyflavone, known as primuletin) was
      synthetized and characterized by ESI mass spectrometry, thermogravimetry, and 1H
      NMR, UV-Vis, and FTIR spectroscopies. In agreement with the experimental results,
      DFT calculations indicated that the flavonoid ligand is coordinated to one of the
      three Cr(III) centers in an O,O-bidentate mode through the 5-hydroxy/4-keto
      groups. In a comparative study involving the uncoordinated primuletin and its
      corresponding complex, systematic reactions with the free radical 2,2-diphenyl-1
      picrylhydrazyl (DPPH) showed that antiradical activity increases upon
      complexation. 

PMID- 25867823
TI  - Insights into the antimicrobial properties of hepcidins: advantages and drawbacks
      as potential therapeutic agents.
AB  - The increasing frequency of multi-drug resistant microorganisms has driven
      research into alternative therapeutic strategies. In this respect, natural
      antimicrobial peptides (AMPs) hold much promise as candidates for the development
      of novel antibiotics. However, AMPs have some intrinsic drawbacks, such as
      partial degradation by host proteases or inhibition by host body fluid
      composition, potential toxicity, and high production costs. This review focuses
      on the hepcidins, which are peptides produced by the human liver with a known
      role in iron homeostasis, as well by numerous other organisms (including fish,
      reptiles, other mammals), and their potential as antibacterial and antifungal
      agents. Interestingly, the antimicrobial properties of human hepcidins are
      enhanced at acidic pH, rendering these peptides appealing for the design of new
      drugs targeting infections that occur in body areas with acidic physiological pH.
      This review not only considers current research on the direct killing activity of
      these peptides, but evaluates the potential application of these molecules as
      coating agents preventing biofilm formation and critically assesses technical
      obstacles preventing their therapeutic application. 

PMID- 25867825
TI  - Exploiting protected maleimides to modify oligonucleotides, peptides and peptide
      nucleic acids.
AB  - This manuscript reviews the possibilities offered by 2,5-dimethylfuran-protected
      maleimides. Suitably derivatized building blocks incorporating the exo Diels
      Alder cycloadduct can be introduced at any position of oligonucleotides, peptide
      nucleic acids, peptides and peptoids, making use of standard solid-phase
      procedures. Maleimide deprotection takes place upon heating, which can be
      followed by either Michael-type or Diels-Alder click conjugation reactions.
      However, the one-pot procedure in which maleimide deprotection and conjugation
      are simultaneously carried out provides the target conjugate more quickly and,
      more importantly, in better yield. This procedure is compatible with conjugates
      involving oligonucleotides, peptides and peptide nucleic acids. A variety of
      cyclic peptides and oligonucleotides can be obtained from peptide and
      oligonucleotide precursors incorporating protected maleimides and thiols. 

PMID- 25867826
TI  - Enantioselective synthesis of cis-decalins using organocatalysis and sulfonyl
      Nazarov reagents.
AB  - The first organocatalytic synthesis of cis-decalins using sulfonyl Nazarov
      reagents is reported. The Jorgensen's catalyst directs this highly
      enantioselective synthesis using different cyclohexenal derivatives. 

PMID- 25867827
TI  - Isolation, identification and cytotoxicity of a new noroleanane-type triterpene
      saponin from Salicornia bigelovii Torr.
AB  - Salicornia bigelovii Torr. has been consumed not only as a popular kind of
      vegetable, but also as a medicinal plant to treat hypertension, cephalalgia,
      scurvy and cancer. The present study was designed to investigate its chemical
      components and cytotoxic activity. A new noroleanane-type triterpene saponin,
      bigelovii C (1), was separated and purified from Salicornia bigelovii Torr.,
      along with four known triterpene saponins 2-5. The structure of bigelovii C was
      elucidated as 3-O-(6-O-butyl ester)-beta-D-glucuropyranosyl-23-aldehyde-30
      norolean-12, 20 (29)-dien-28-oic acid-28-O-beta-D-glucopyranoside, according to
      various spectroscopic analysis and chemical characteristics. Besides Compounds 3
      and 5, bigelovii C had potent cytotoxicity against three human cancer cell lines,
      MCF7 (breast cancer), Lovo (colon cancer) and LN229 (glioblastoma), especially
      MCF7. Bigelovii C inhibited the growth of MCF7 cells in dose- and time-dependent
      manners. Flow cytometry analysis revealed that the percentage of apoptotic cells
      significantly increased upon bigelovii C treatment. Rh123 staining assay
      indicated that bigelovii C reduced the mitochondrial membrane potential. The
      mechanism of cell death by bigelovii C may be attributed to the downregulation of
      Bcl-2 and upregulation of Bax, cleaved caspase-9, caspase-7 and PARP. These
      results suggested that bigelovii C may impart health benefits when consumed and
      should be regarded as a potential chemopreventative agent for cancer. 

PMID- 25867828
TI  - Novel microsatellite markers acquired from Rubus coreanus Miq. and cross
      amplification in other Rubus species.
AB  - The Rubus genus consists of more than 600 species that are distributed globally.
      Only a few Rubus species, including raspberries and blueberries, have been
      domesticated. Genetic diversity within and between Rubus species is an important
      resource for breeding programs. We developed genomic microsatellite markers using
      an SSR-enriched R. coreanus library to study the diversity of the Rubus species.
      Microsatellite motifs were discovered in 546 of 646 unique clones, and a
      dinucleotide repeat was the most frequent (75.3%) type of repeat. From 97
      microsatellite loci with reproducible amplicons, we acquired 29 polymorphic
      microsatellite markers in the Rubus coreanus collection. The transferability
      values ranged from 59.8% to 84% across six Rubus species, and Rubus parvifolius
      had the highest transferability value (84%). The average number of alleles and
      the polymorphism information content were 5.7 and 0.541, respectively, in the R.
      coreanus collection. The diversity index of R. coreanus was similar to the values
      reported for other Rubus species. A phylogenetic dendrogram based on SSR profiles
      revealed that seven Rubus species could be allocated to three groups, and that R.
      coreanus was genetically close to Rubus crataegifolius (mountain berry). These
      new microsatellite markers might prove useful in studies of the genetic
      diversity, population structure, and evolutionary relationships among Rubus
      species. 

PMID- 25867829
TI  - Antioxidant and hepatoprotective effect of Penthorum chinense Pursh extract
      against t-BHP-induced liver damage in L02 cells.
AB  - Penthorum chinense Pursh (P. chinense), a traditional Chinese medicine used by
      the Chinese Miao minority, has been used to treat liver diseases for a long time.
      However, the mechanism behind the liver protective effects of P. chinense remains
      unclear so far. The aim of the present study was to investigate the
      hepatoprotective effect of P. chinense and its possible mechanism(s).
      Immortalized normal human normal liver L02 cells were used to evaluate the
      protective effect of P. chinense aqueous extract against tert-butyl hydroperoxide
      (t-BHP)-induced liver cell damage. Treatment with P. chinense aqueous extract
      significantly protected L02 cells from t-BHP-induced cytotoxicity, prevented t
      BHP-induced reactive oxygen species (ROS) generation and decreased the percentage
      of apoptosis by inhibiting the mitochondrial apoptotic pathway. This study
      demonstrates that P. chinense is a potential hepatoprotective agent in t-BHP
      induced liver cell damage, which may benefit the further application of P.
      chinense in the clinic. 

PMID- 25867824
TI  - Heparin/Heparan sulfate proteoglycans glycomic interactome in angiogenesis:
      biological implications and therapeutical use.
AB  - Angiogenesis, the process of formation of new blood vessel from pre-existing
      ones, is involved in various intertwined pathological processes including virus
      infection, inflammation and oncogenesis, making it a promising target for the
      development of novel strategies for various interventions. To induce
      angiogenesis, angiogenic growth factors (AGFs) must interact with pro-angiogenic
      receptors to induce proliferation, protease production and migration of
      endothelial cells (ECs). The action of AGFs is counteracted by antiangiogenic
      modulators whose main mechanism of action is to bind (thus sequestering or
      masking) AGFs or their receptors. Many sugars, either free or associated to
      proteins, are involved in these interactions, thus exerting a tight regulation of
      the neovascularization process. Heparin and heparan sulfate proteoglycans
      undoubtedly play a pivotal role in this context since they bind to almost all the
      known AGFs, to several pro-angiogenic receptors and even to angiogenic
      inhibitors, originating an intricate network of interaction, the so called
      "angiogenesis glycomic interactome". The decoding of the angiogenesis glycomic
      interactome, achievable by a systematic study of the interactions occurring among
      angiogenic modulators and sugars, may help to design novel antiangiogenic
      therapies with implications in the cure of angiogenesis-dependent diseases. 

PMID- 25867830
TI  - An ultra-high performance liquid chromatographic-tandem mass spectrometric method
      for the determination of sinomenine in human plasma after transdermal delivery of
      the zhengqing fengtongning injection.
AB  - A sensitive, precise and selective ultra-high performance liquid chromatography
      method coupled with triple-quadrupole mass spectrometry was developed and
      validated for the determination of trace amounts of sinomenine (ng/mL) in minute
      volumes of human plasma. Fifty microliter plasma samples were precipitated using
      methanol to extract sinomenine. Separation was carried out on a C18 column with a
      water and acetonitrile mobile phase gradient with formic acid as an additive. The
      mass spectrometry data were obtained in the positive ion mode, and the transition
      of multiple reactions was monitored at m/z 330.2->181.0 for sinomenine
      quantification. The working assay range for sinomenine was linear from 0.1173 to
      15.02 ng/mL with the lower limit of quantification of 0.1173 ng/mL. The precision
      and accuracy of the method was less than 15% in intra-day and inter-day
      experiments with a matrix effect of less than 6.5%. After validation, the
      quantitative method was applied to analyze sinomenine levels in human plasma
      after transdermal delivery of the Zhengqing Fengtongning Injection. The results
      showed that some samples contained sinomenine within the concentration range
      0.4131-4.407 ng/mL. 

PMID- 25867831
TI  - Recycling antibiotics into GUMBOS: a new combination strategy to combat multi
      drug-resistant bacteria.
AB  - The emergence of multi-drug-resistant bacteria, coupled with the lack of new
      antibiotics in development, is fast evolving into a global crisis. New strategies
      utilizing existing antibacterial agents are urgently needed. We propose one such
      strategy in which four outmoded beta-lactam antibiotics (ampicillin,
      carbenicillin, cephalothin and oxacillin) and a well-known antiseptic
      (chlorhexidine di-acetate) were fashioned into a group of uniform materials based
      on organic salts (GUMBOS) as an alternative to conventional combination drug
      dosing strategies. The antibacterial activity of precursor ions (e.g.,
      chlorhexidine diacetate and beta-lactam antibiotics), GUMBOS and their unreacted
      mixtures were studied with 25 clinical isolates with varying antibiotic
      resistance using a micro-broth dilution method. Acute cytotoxicity and
      therapeutic indices were determined using fibroblasts, endothelial and cervical
      cell lines. Intestinal permeability was predicted using a parallel artificial
      membrane permeability assay. GUMBOS formed from ineffective beta-lactam
      antibiotics and cytotoxic chlorhexidine diacetate exhibited unique
      pharmacological properties and profound antibacterial activity at lower
      concentrations than the unreacted mixture of precursor ions at equivalent
      stoichiometry. Reduced cytotoxicity to invasive cell types commonly found in
      superficial and chronic wounds was also observed using GUMBOS. GUMBOS show
      promise as an alternative combination drug strategy for treating wound infections
      caused by drug-resistant bacteria. 

PMID- 25867832
TI  - Copolymers of vinyl-containing benzoxazine with vinyl monomers as precursors for
      high performance thermosets.
AB  - A benzoxazine containing a vinyl group (P-4va) was prepared by the reaction of
      phenol, 4-vinylaniline, and paraformaldehyde. A differential scanning calorimetry
      (DSC) study revealed that ring-opening polymerization of the benzoxazine and
      chain polymerization of the vinyl group occurred in the same temperature range.
      When 2,2'-azobisisobutyronitrile was added as a radical initiator to P-4va,
      however, only the vinyl groups were polymerized at lower temperature, giving
      oligo(P-4va) that contains pendent benzoxazine units. Radical copolymerization of
      P-4va with various vinyl monomers such as styrene, methyl methacrylate (MMA), and
      n-butyl acrylate (BuA) was examined. The chemical structure of the copolymers was
      confirmed by FT-IR and 1H-NMR to be one of polyolefins bearing benzoxazine units
      as the pendant groups. The weight-average molecular weights of the copolymers
      determined by size exclusion chromatography were to be in the range of 1900
      51,500 depending on the comonomers. DSC of the copolymers showed that the maxima
      of the exothermic peaks corresponding to the ring-opening polymerization of the
      pendent benzoxazine units were observed in the temperature range of 229-250 
      degrees C. Thermal cure up to 240  degrees C of the copolymer films afforded
      homogenous transparent films with improved thermal properties. Tough cured film
      was obtained by the copolymerization with MMA, while a tough and flexible film
      was obtained by the copolymerization with BuA. 

PMID- 25867833
TI  - Methamphetamine induces DNA damage in specific regions of the female rat brain.
AB  - Methamphetamine (METH) is a highly addictive psychostimulant that has been shown
      to produce neurotoxicity. Methamphetamine increases the release of dopamine by
      reversing the direction of monoamine transporter proteins, leading to the
      formation of reactive oxygen species in the brain. In this study, we examined the
      effect of METH on DNA damage in vivo using the single cell gel electrophoresis
      assay (comet assay) under two different conditions. Rats treated with multiple
      doses of METH (10 mg/kg * 4) showed significant levels of DNA damage in the
      nucleus accumbens and striatum, both dopamine-rich areas. In contrast, a single
      dose of METH did not lead to significant levels of DNA damage in any of the
      dopamine-rich brain regions that were tested. Overall, the results of our study
      demonstrate that METH produces greater oxidative DNA damage in brain areas that
      receive greater dopamine innervation.

PMID- 25867834
TI  - Explicit and inferred motives for nonsuicidal self-injurious acts and urges in
      borderline and avoidant personality disorders.
AB  - Nonsuicidal self-injury (NSSI) is a perplexing phenomenon that may have differing
      motives. The present study used experience sampling methods (ESM) which inquired
      explicitly about the motives for NSSI, but also enabled a temporal examination of
      the antecedents/consequences of NSSI; these allow us to infer other motives which
      were not explicitly endorsed. Adults (n = 152, aged 18-65) with borderline
      personality disorder (BPD), avoidant personality disorder (APD), or no
      psychopathology participated in a 3-week computerized diary study. We examined 5
      classes of explicit motives for engaging in NSSI, finding support primarily for
      internally directed rather than interpersonally directed ones. We then used
      multilevel regression to examine changes in affect, cognition, and behavior
      surrounding moments of NSSI acts/urges compared with control moments (i.e.,
      without NSSI). We examined changes in 5 scales of inferred motives, designed to
      correspond to the 5 classes of explicit motives. The results highlight differing
      motives for NSSI among individuals with BPD and APD, with some similarities
      (mostly in the explicit motives) and some differences (mostly in the inferred
      motives) between the disorders. Despite their infrequent explicit endorsement,
      fluctuations in interpersonally oriented scales were found surrounding NSSI
      acts/urges. This highlights the need to continue attending to interpersonal
      aspects of NSSI in research and in clinical practice. Additionally, NSSI urges,
      like acts, were followed by decline in affective/interpersonal distress (although
      in a delayed manner). Thus, interventions that build distress tolerance and
      enhance awareness for affective changes, and for antecedent/consequence patterns
      in NSSI, could help individuals resist the urge to self-injure.

PMID- 25867835
TI  - A latent variable analysis of the Psychopathy Checklist-Revised and behavioral
      inhibition system/behavioral activation system factors in North American and
      Swedish offenders.
AB  - An influential neurobiological model of personality is the Reinforcement
      Sensitivity Theory, which postulates how basic motivational systems (behavioral
      activation system [BAS], behavioral inhibition system [BIS]) can help account for
      the development and expression of individual differences in personality. Earlier
      research has documented a link between psychopathic personality and the BIS/BAS
      scale (Carver & White, 1994), which was developed to measure the behavioral
      inhibition and activation systems. However, no studies have examined how latent
      BIS/BAS factors and the 4 empirically derived Psychopathy Checklist-Revised (PCL
      R) psychopathy factors (Hare & Neumann, 2008) are associated across different
      cultures. In the current study, structural equation modeling was used to
      determine how the 4 PCL-R factors were able to predict BIS/BAS factors using 2
      large independent samples of male offenders (North American N = 908; Swedish N =
      242). The results were in line with theory and revealed a negative relationship
      between the PCL-R Affective factor and the BIS factor as well as positive
      relationships between the PCL-R Antisocial and Lifestyle factors with the BAS
      factor. Overall, the results of the current study provide evidence of cross
      cultural generalizability for the associations between the PCL-R factors and the
      BIS-BAS factors. Taken together, the PCL-R psychopathy factors were able to
      account for meaningful variance in the BIS-BAS factors and further support a
      dimensional approach to understanding the psychopathy construct across cultures.

PMID- 25867836
TI  - Impulsivity-related traits and their relation to DSM-5 section II and III
      personality disorders.
AB  - Difficulties with impulse control are considered a core feature of personality
      disorders (PDs) as assessed by the Diagnostic and Statistical Manual of Mental
      Disorders (5th edition [DSM-5]; American Psychiatric Association, 2013). Despite
      this, there has been relatively little examination of the manner in which DSM-5
      PDs are characterized by multidimensional models of impulsivity that parse this
      broad umbrella construct into smaller, more unidimensional constructs. Using the
      UPPS model and measure of impulsivity (Whiteside & Lynam, 2001), the relations
      between 4 impulsivity-related traits and interview-rated scores on both DSM-5
      Section II and III PDs and PD traits were examined in a community sample of
      individuals currently receiving psychological or psychiatric care (N = 106). As
      expected, the UPPS traits manifested correlations with the new Section III trait
      model that were generally consistent with the assertion that this new DSM-5 trait
      model reflects a pathological variant of the Five-Factor Model (FFM; e.g., UPPS
      traits associated with FFM conscientiousness were most strongly related to DSM-5
      disinhibition traits). Overall, the UPPS traits accounted best for variance in
      DSM-5 Section II and III Cluster B PDs, consistent with these PDs being
      characterized, in part, by emotionally and cognitively based forms of
      impulsivity.

PMID- 25867837
TI  - Domains of psychopathy: evaluating the structure of a lexical model of
      psychopathic personality disorder.
AB  - This study examines the structure of the Comprehensive Assessment of Psychopathic
      Personality (CAPP) from a card sort perspective. The CAPP is a lexically based
      construct map of psychopathy comprising 33 symptoms organized by its developers
      into 6 broad functional domains of personality (i.e., Attachment, Behavioral,
      Cognitive; Dominance; Emotional, Self). Groups of mental health workers and
      students were asked to sort the CAPP symptoms into the model's 6 proposed
      domains. Overall, both mental health workers and students were able to categorize
      the symptoms speedily and intuitively according to model. This suggests that the
      CAPP model's hierarchical structure is plausible, and that the lexical nature of
      the model is successful in facilitating people's ability to understand features
      of psychopathy in a way that requires limited cognitive effort. Together, these
      findings support the validity of the CAPP model as a lexically based concept map
      of psychopathy. Yet, some exceptions to the overall pattern of agreement with
      model were identified.

PMID- 25867838
TI  - The facets of identity: personality pathology assessment through the Inventory of
      Personality Organization.
AB  - This work aims to further validate the object-relations-based model of
      personality pathology assessment, evaluating the psychometric properties of the
      Italian version of the Inventory of Personality Organization (IPO), a self-report
      instrument for the assessment of personality organization according to O.
      Kernberg's model of personality pathology. Six hundred ninety-six nonclinical
      volunteers and 121 psychiatric patients completed a set of questionnaires
      including the IPO, the Severity Indices of Personality Problems, the Borderline
      Personality Disorder Checklist, the Response Evaluation Measure 71, and the
      Symptom Checklist 90-Revised. Confirmatory factor-analyses on the IPO items
      supported the 1-, 2-, 3-, and 4-factor solutions. The last (Instability of sense
      of self/others, Instability of goals, Instability of behaviors, Psychosis)
      resulted in relatively better fit indexes. Invariance across samples
      (nonclinical, clinical) and gender was confirmed. The 4 IPO subscales showed good
      levels of internal coherence and, in the nonclinical sample, good test-retest
      reliability. Associations with the convergent measures were in line with
      theoretical expectations and supported the benefit of adopting a 4-factor
      solution. The 4 factors showed the expected criterion relations: All the
      dimensions discriminated between clinical and nonclinical subjects, whereas only
      Instability of self/others and Instability of goals discriminated patients with
      borderline personality disorder from patients with other diagnoses. Our results
      suggest that the Italian version of the IPO is a reliable and valid tool for the
      assessment of personality organization according to Kernberg's model. Results are
      discussed in the context of the current directions in the evaluation of
      personality disorders proposed by the Diagnostic and Statistical Manual of Mental
      Disorders, 5th edition.

PMID- 25867839
TI  - Effect of maternal autonomy and relatedness and borderline personality disorder
      on adolescent symptomatology.
AB  - Several theories propose a relationship between deficits in autonomy and
      relatedness and the development of borderline personality disorder (BPD).
      Empirical work supports relationships between maternal BPD and adolescent
      symptomatology, as well as between maternal autonomy and relatedness and
      adolescent symptomatology. However, no study has examined how individuals with
      BPD differ from normative comparisons on autonomy and relatedness, or whether
      mothers' BPD mediates the relationship between their autonomy and relatedness and
      their adolescents' symptomatology. We sampled 28 mothers with BPD and their
      adolescents aged 14-17 years, as well as 28 normative comparisons matched on
      demographic variables. We assessed BPD as a categorical diagnosis and along a
      continuum of self-reported borderline features. In a videotaped problem-solving
      interaction, controlling for current major depressive disorder, mothers with BPD
      were less likely to promote and more likely to inhibit relatedness, and they were
      marginally more likely to inhibit but equally likely to promote autonomy with
      their adolescents. Mothers' total borderline features mediated the relationship
      between mothers' promotion of autonomy plus relatedness and adolescent
      internalizing and externalizing symptoms (anxious depression, withdrawn
      depression, somatic problems, rule breaking, and aggression) and adolescent
      borderline features (affective instability and self-harm). Mothers' total
      borderline features also mediated the relationship between mothers' inhibition of
      autonomy plus relatedness and adolescent internalizing and externalizing symptoms
      (anxious depression, withdrawn depression, somatic problems, and aggression but
      not rule breaking) and adolescent borderline features (affective instability and
      self-harm). We discuss findings in terms of light shed on BPD and the effect of
      maternal BPD on adolescent development.

PMID- 25867842
TI  - Consensus building: commentary on "choice impulsivity" and "rapid-response
      impulsivity" articles by Hamilton and colleagues.

PMID- 25867840
TI  - Rapid-response impulsivity: definitions, measurement issues, and clinical
      implications.
AB  - Impulsivity is a multifaceted construct that is a core feature of multiple
      psychiatric conditions and personality disorders. However, progress in
      understanding and treating impulsivity is limited by a lack of precision and
      consistency in its definition and assessment. Rapid-response impulsivity (RRI)
      represents a tendency toward immediate action that occurs with diminished
      forethought and is out of context with the present demands of the environment.
      Experts from the International Society for Research on Impulsivity (InSRI) met to
      discuss and evaluate RRI measures in terms of reliability, sensitivity, and
      validity, with the goal of helping researchers and clinicians make informed
      decisions about the use and interpretation of findings from RRI measures. Their
      recommendations are described in this article. Commonly used clinical and
      preclinical RRI tasks are described, and considerations are provided to guide
      task selection. Tasks measuring two conceptually and neurobiologically distinct
      types of RRI, "refraining from action initiation" (RAI) and "stopping an ongoing
      action" (SOA) are described. RAI and SOA tasks capture distinct aspects of RRI
      that may relate to distinct clinical outcomes. The InSRI group recommends that
      (a) selection of RRI measures should be informed by careful consideration of the
      strengths, limitations, and practical considerations of the available measures;
      (b) researchers use both RAI and SOA tasks in RRI studies to allow for direct
      comparison of RRI types and examination of their associations with clinically
      relevant measures; and (c) similar considerations be made for human and nonhuman
      studies in an effort to harmonize and integrate preclinical and clinical
      research.

PMID- 25867843
TI  - Fractionating impulsivity: commentary on "choice impulsivity" and "rapid-response
      impulsivity" articles by Hamilton and colleagues.

PMID- 25867844
TI  - The misnomer of impulsivity: commentary on "choice impulsivity" and "rapid
      response impulsivity" articles by Hamilton and colleagues.

PMID- 25867841
TI  - Choice impulsivity: Definitions, measurement issues, and clinical implications.
AB  - Impulsivity critically relates to many psychiatric disorders. Given the
      multifaceted construct that impulsivity represents, defining core aspects of
      impulsivity is vital for the assessment and understanding of clinical conditions.
      Choice impulsivity (CI), involving the preferential selection of smaller sooner
      rewards over larger later rewards, represents one important type of impulsivity.
      The International Society for Research on Impulsivity (InSRI) convened to discuss
      the definition and assessment of CI and provide recommendations regarding
      measurement across species. Commonly used preclinical and clinical CI behavioral
      tasks are described, and considerations for each task are provided to guide CI
      task selection. Differences in assessment of CI (self-report, behavioral) and
      calculating CI indices (e.g., area-under-the-curve, indifference point, and
      steepness of discounting curve) are discussed along with properties of specific
      behavioral tasks used in preclinical and clinical settings. The InSRI group
      recommends inclusion of measures of CI in human studies examining impulsivity.
      Animal studies examining impulsivity should also include assessments of CI and
      these measures should be harmonized in accordance with human studies of the
      disorders being modeled in the preclinical investigations. The choice of specific
      CI measures to be included should be based on the goals of the study and existing
      preclinical and clinical literature using established CI measures.

PMID- 25867845
TI  - In vivo, percutaneous, needle based, optical coherence tomography of renal
      masses.
AB  - Optical coherence tomography (OCT) is the optical equivalent of ultrasound
      imaging, based on the backscattering of near infrared light. OCT provides real
      time images with a 15 um axial resolution at an effective tissue penetration of 2
      3 mm. Within the OCT images the loss of signal intensity per millimeter of tissue
      penetration, the attenuation coefficient, is calculated. The attenuation
      coefficient is a tissue specific property, providing a quantitative parameter for
      tissue differentiation. Until now, renal mass treatment decisions have been made
      primarily on the basis of MRI and CT imaging characteristics, age and
      comorbidity. However these parameters and diagnostic methods lack the finesse to
      truly detect the malignant potential of a renal mass. A successful core biopsy or
      fine needle aspiration provides objective tumor differentiation with both
      sensitivity and specificity in the range of 95-100%. However, a non-diagnostic
      rate of 10-20% overall, and even up to 30% in SRMs, is to be expected, delaying
      the diagnostic process due to the frequent necessity for additional biopsy
      procedures. We aim to develop OCT into an optical biopsy, providing real-time
      imaging combined with on-the-spot tumor differentiation. This publication
      provides a detailed step-by-step approach for percutaneous, needle based, OCT of
      renal masses. 

PMID- 25867846
TI  - Biphenotypic B-cell lymphoma in 2 cats.
AB  - The clinical and pathologic features of biphenotypic B-cell lymphoma in 2 cats
      are reported. Clinical presentation varied from multiple cutaneous masses
      identified on the thigh in one cat to signs of lethargy from acute hemorrhage due
      to neoplastic infiltration of one kidney in the other. Cytology and
      histopathology confirmed round cell neoplasia in both cats and immunochemical
      staining demonstrated expression of both B- and T-lymphocyte markers by the
      neoplastic cells in both animals. In PCR analysis of antigen receptor gene
      rearrangement, clonal rearrangement of B-cell receptor genes and polyclonal T
      cell receptor gene rearrangement were demonstrated in both lymphomas. These
      findings were consistent with a diagnosis of B-cell lymphoma with aberrant CD3
      expression in both cases. Clinical progression of disease post diagnosis was
      rapid in both cats, suggesting a poor prognosis for this lymphoma type. Although
      bigenotypic receptor rearrangement of lymphoma cells appears relatively common,
      this is the first known report of actual biphenotypic lymphoma in cats. 

PMID- 25867847
TI  - Changes in mitochondrial enzymatic activities of monocytes during prolonged
      hypobaric hypoxia and influence of antioxidants: A randomized controlled study.
AB  - OBJECTIVES: Exposure to high altitudes is associated with oxidative cellular
      damage due to the increased level of reactive oxygen and nitrogen species and
      altered activity of antioxidant systems. Subjects were submitted to prolonged
      hypoxia, to evaluate changes in mitochondrial enzyme activities of monocytes and
      their attenuation by supplementation with antioxidants. METHODS: Twelve subjects
      were randomly assigned to receive antioxidant supplements or placebo prior to and
      during an expedition to Pik Lenin (7145 m). Monocytes were isolated from blood
      samples to determine the activity of mitochondrial enzymes cytochrome c oxidase
      and citrate synthase at 490 m (baseline) and at the altitudes of 3550 m, 4590 m,
      and 5530 m. RESULTS: An increase in citrate synthase activity at all altitudes
      levels was observed. Hypoxia induced an increase in the activity of cytochrome c
      oxidase only at 4590 m. Neither citrate synthase activity nor cytochrome c
      oxidase activity differed between the subjects receiving antioxidant supplements
      and those receiving placebo. CONCLUSIONS: Hypoxia leads to an increase in citrate
      synthase activity of monocyte mitochondria as a marker of mitochondrial mass,
      which is not modified by antioxidant supplementation. The increase in
      mitochondrial mass may represent a compensatory mechanism to preserve oxidative
      phosphorylation of monocytes at high altitudes.

PMID- 25867848
TI  - Rapid reverse genetic screening using CRISPR in zebrafish.
AB  - Identifying genes involved in biological processes is critical for understanding
      the molecular building blocks of life. We used engineered CRISPR (clustered
      regularly interspaced short palindromic repeats) to efficiently mutate specific
      loci in zebrafish (Danio rerio) and screen for genes involved in vertebrate
      biological processes. We found that increasing CRISPR efficiency by injecting
      optimized amounts of Cas9-encoding mRNA and multiplexing single guide RNAs
      (sgRNAs) allowed for phenocopy of known mutants across many phenotypes in
      embryos. We performed a proof-of-concept screen in which we used intersecting,
      multiplexed pool injections to examine 48 loci and identified two new genes
      involved in electrical-synapse formation. By deep sequencing target loci, we
      found that 90% of the genes were effectively screened. We conclude that CRISPR
      can be used as a powerful reverse genetic screening strategy in vivo in a
      vertebrate system. 

PMID- 25867849
TI  - High-resolution whole-brain staining for electron microscopic circuit
      reconstruction.
AB  - Currently only electron microscopy provides the resolution necessary to
      reconstruct neuronal circuits completely and with single-synapse resolution.
      Because almost all behaviors rely on neural computations widely distributed
      throughout the brain, a reconstruction of brain-wide circuits-and, ultimately,
      the entire brain-is highly desirable. However, these reconstructions require the
      undivided brain to be prepared for electron microscopic observation. Here we
      describe a preparation, BROPA (brain-wide reduced-osmium staining with pyrogallol
      mediated amplification), that results in the preservation and staining of
      ultrastructural details throughout the brain at a resolution necessary for
      tracing neuronal processes and identifying synaptic contacts between them. Using
      serial block-face electron microscopy (SBEM), we tested human annotator ability
      to follow neural 'wires' reliably and over long distances as well as the ability
      to detect synaptic contacts. Our results suggest that the BROPA method can
      produce a preparation suitable for the reconstruction of neural circuits spanning
      an entire mouse brain. 

PMID- 25867850
TI  - In vivo cell-cycle profiling in xenograft tumors by quantitative intravital
      microscopy.
AB  - Quantification of cell-cycle state at a single-cell level is essential to
      understand fundamental three-dimensional (3D) biological processes such as tissue
      development and cancer. Analysis of 3D in vivo images, however, is very
      challenging. Today's best practice, manual annotation of select image events,
      generates arbitrarily sampled data distributions, which are unsuitable for
      reliable mechanistic inferences. Here, we present an integrated workflow for
      quantitative in vivo cell-cycle profiling. It combines image analysis and machine
      learning methods for automated 3D segmentation and cell-cycle state
      identification of individual cell-nuclei with widely varying morphologies
      embedded in complex tumor environments. We applied our workflow to quantify cell
      cycle effects of three antimitotic cancer drugs over 8 d in HT-1080 fibrosarcoma
      xenografts in living mice using a data set of 38,000 cells and compared the
      induced phenotypes. In contrast to results with 2D culture, observed mitotic
      arrest was relatively low, suggesting involvement of additional mechanisms in
      their antitumor effect in vivo. 

PMID- 25867851
TI  - Highly Enantioselective Acylation of Acyclic Meso 1,3-Diols through Synergistic
      Isothiourea-Catalyzed Desymmetrization/Chiroablative Kinetic Resolution.
AB  - A general and highly efficient organocatalyzed desymmetrization of acyclic meso
      1,3-diols through acyl transfer using chiral isothioureas is described. The
      introduction of pi-systems in the acyclic substrates provided new opportunities
      in terms of reactivity, enantioselectivity and synthetic potential. To reach this
      high level of enantioselectivity (up to er >99:1), the reaction proceeds through
      a synergistic mechanism involving a desymmetrization reaction and a chiroablative
      kinetic resolution process. This methodology was used with success as the sole
      enantioselective catalytic step (developed on a gram scale) to achieve the total
      synthesis of the antiosteoporotic diarylheptanoid (-)-diospongin A (7 steps). 

PMID- 25867852
TI  - Does selection bias explain the obesity paradox among individuals with
      cardiovascular disease?
AB  - OBJECTIVES: The objectives of this article are to demonstrate that the obesity
      paradox may be explained by collider stratification bias and to estimate the
      biasing effects of unmeasured common causes of cardiovascular disease (CVD) and
      mortality on the observed obesity-mortality relationship. METHODS: We use
      directed acyclic graphs, regression modeling, and sensitivity analyses to explore
      whether the observed protective effect of obesity among individuals with CVD can
      be plausibly attributed to selection bias. Data from the third National Health
      and Examination Survey was used for the analyses. RESULTS: The adjusted total
      effect of obesity on mortality was a risk difference (RD) of 0.03 (95% confidence
      interval [CI]: 0.02, 0.05). However, the controlled direct effect of obesity on
      mortality among individuals without CVD was RD = 0.03 (95% CI: 0.01, 0.05) and RD
      = -0.12 (95% CI: -0.20, -0.04) among individuals with CVD. The adjusted total
      effect estimate demonstrates an increased number of deaths among obese
      individuals relative to nonobese counterparts, whereas the controlled direct
      effect shows a paradoxical decrease in morality among obese individuals with CVD.
      CONCLUSIONS: Sensitivity analysis demonstrates unmeasured confounding of the
      mediator-outcome relationship provides a sufficient explanation for the observed
      protective effect of obesity on mortality among individuals with CVD.

PMID- 25867853
TI  - Surface enhanced Raman spectroscopy detection of biomolecules using EBL
      fabricated nanostructured substrates.
AB  - Fabrication and characterization of conjugate nano-biological systems interfacing
      metallic nanostructures on solid supports with immobilized biomolecules is
      reported. The entire sequence of relevant experimental steps is described,
      involving the fabrication of nanostructured substrates using electron beam
      lithography, immobilization of biomolecules on the substrates, and their
      characterization utilizing surface-enhanced Raman spectroscopy (SERS). Three
      different designs of nano-biological systems are employed, including protein A,
      glucose binding protein, and a dopamine binding DNA aptamer. In the latter two
      cases, the binding of respective ligands, D-glucose and dopamine, is also
      included. The three kinds of biomolecules are immobilized on nanostructured
      substrates by different methods, and the results of SERS imaging are reported.
      The capabilities of SERS to detect vibrational modes from surface-immobilized
      proteins, as well as to capture the protein-ligand and aptamer-ligand binding are
      demonstrated. The results also illustrate the influence of the surface
      nanostructure geometry, biomolecules immobilization strategy, Raman activity of
      the molecules and presence or absence of the ligand binding on the SERS spectra
      acquired. 

PMID- 25867854
TI  - Targeted nanoscale magnetic hyperthermia: challenges and potentials of peptide
      based targeting.

PMID- 25867855
TI  - Highlights from the latest articles in nano-oncology.

PMID- 25867856
TI  - Triple combination of carbosilane dendrimers, tenofovir and maraviroc as
      potential microbicide to prevent HIV-1 sexual transmission.
AB  - AIM: To research the synergistic activity by triple combinations of carbosilane
      dendrimers with tenofovir and maraviroc as topical microbicide. METHODS:
      Cytotoxicity, anti-HIV-1 activity, vaginal irritation and histological analysis
      of triple combinations were determined. Analysis of combined effects and the
      median effective concentration were performed using CalcuSyn software. RESULTS:
      Combinations showed a greater broad-spectrum anti-HIV-1 activity than the single
      drug, and preserved this activity in acid environment or seminal fluid. The
      strongest combinations were G2-STE16/G2-S24P/tenofovir, G2-STE16/G2-S16/maraviroc
      and G2-STE16/tenofovir/maraviroc at 2:2:1, 10:10:1 10:5:1 ratios, respectively.
      They demonstrated strong synergistic activity profile due to the weighted average
      combination indices varied between 0.06 and 0.38. No irritation was detected in
      female BALB/c mice. CONCLUSION: The three-drug combination increases their
      antiviral potency and act synergistically as potential microbicide.

PMID- 25867857
TI  - Enhancement of anti-tumor effect of particulate vaccine delivery system by
      'bacteriomimetic' CpG functionalization of poly-lactic-co-glycolic acid
      nanoparticles.
AB  - AIM: Low immunogenicity remains a major obstacle in realizing the full potential
      of cancer vaccines. In this study, we evaluated CpG-coated tumor antigen (Tag)
      encapsulating 'bacteriomimetic' nanoparticles (CpG-nanoparticle [NP]-Tag NPs) as
      an approach to enhance anti-tumor immunity. MATERIALS & METHODS: CpG-NP-Tag NPs
      were synthesized, characterized for their physicochemical properties and tested
      in vivo. RESULTS: We found CpG predosing followed by intraperitoneal (IP)
      immunization with CpG-NP-Tag NPs significantly attenuated tumor growth in female
      BALB/c mice compared with respective controls. Histopathological and
      Immunofluorescence data revealed CpG-NP-Tag tumors had lower proliferation,
      higher apoptotic activity, greater CD4(+) and CD8(+) T cell infiltration as well
      as higher IFN-gamma levels as compared with control groups. CONCLUSION: Our
      findings suggest CpG-NP-Tag NPs can enhance anti-tumor effect of nanoparticulate
      tumor vaccination system.

PMID- 25867858
TI  - Preferential magnetic targeting of carbon nanotubes to cancer sites: noninvasive
      tracking using MRI in a murine breast cancer model.
AB  - AIM: This study evaluated the improvement in magnetic targeting of single-walled
      carbon nanotubes (SWCNTs) in a 4T1-induced breast cancer murine model and
      compared their enhanced delivery with active targeted SWCNTs conjugated with a
      specific antibody for prospective applications as drug-delivery nanocarriers.
      MATERIALS & METHODS: Polyvinylpyrrolidone SWCNTs, loaded with iron oxide
      nanoparticles to improve their magnetic resonance detection and magnet attraction
      using an optimized flexible magnet positioned over the tumor site were developed.
      They were equally conjugated with Endoglin/CD105 antibody for SWCNTs active
      targeting. A noninvasive MRI protocol was then optimized to allow in vivo imaging
      of tumor site, sensitive detection of SWCNTs and apparent diffusion coefficient
      measurements. Special focus was devoted to evaluate the biocompatibility of the
      used SWCNTs. RESULTS: Iron-tagged SWCNTs exhibited very high magnetic resonance
      r2* relaxivities allowing their sensitive detection using noninvasive MRI and
      enhanced targeting using the magnet. Biocompatibility evaluations confirmed their
      safety for animal administration. Both T2* and apparent diffusion coefficient
      measurements confirmed their enhanced magnetic targeting starting from 2 h
      postinjection while a lower, but statistically significant enhanced targeting of
      antibody-conjugated active targeting was observed starting from 24 h
      postinjection of iron-tagged SWCNT + CD105 samples. CONCLUSION: These results
      demonstrate the efficiency of magnetic targeting to specifically deliver higher
      load of iron-tagged SWCNTs as novel nanocarriers for cancer theranostics and
      allow their sensitive detection using noninvasive MRI.

PMID- 25867859
TI  - Osteoclastogenesis/osteoblastogenesis using human bone marrow-derived cocultures
      on nanotopographical polymer surfaces.
AB  - BACKGROUND: Optimised nanotopography with controlled disorder (NSQ50) has been
      shown to stimulate osteogenesis and new bone formation in vitro. Following
      osteointegration the implant interface must undergo constant remodeling without
      inducing immune response. AIM: We aimed to assess the effect of nanotopography on
      bone remodelling using osteoclast and osteoblast cocultures. MATERIALS & METHODS:
      We developed a novel osteoblast/osteoclast coculture using solely human bone
      marrow derived mesenchymal and hematopeotic progenitor cells without extraneous
      supplementation. The coculture was been applied to NSQ50 or flat control
      polycarbonate substrates and assessed using immunohistochemical and
      immunofluorescent microscopy, scanning electron microscopy and quantitative
      reverse-transcription PCR methods. RESULTS: These confirm the presence of mature
      osteoclasts, osteoblasts and bone formation in coculture. Osteoblast
      differentiation increased on NSQ50, with no significant difference in osteoclast
      differentiation. CONCLUSION: Controlled disorder nanotopography appears to be
      selectively bioactive. We recommend this coculture method to be a better in vitro
      approximation of the osseous environment encountered by implants.

PMID- 25867860
TI  - Nanomaterials for enhanced immunity as an innovative paradigm in nanomedicine.
AB  - Since the advent of nanoparticle technology, novel and versatile properties of
      nanomaterials have been introduced, which has constantly expanded their
      applications in therapeutics. Introduction of nanomaterials for immunomodulation
      has opened up new avenues with tremendous potential. Interesting properties of
      nanoparticles, such as adjuvanticity, capability to enhance cross-presentation,
      polyvalent presentation, siRNA delivery for silencing of immunesuppressive gene,
      targeting and imaging of immune cells have been known to have immense utility in
      vaccination and immunotherapy. A thorough understanding of the merits associated
      with nanomaterials is crucial for designing of modular and versatile
      nanovaccines, for improved immune response. With the emerging prerequisites of
      vaccination, nanomaterial-based immune stimulation, seems to be capable of taking
      the field of immunization to a next higher level. 

PMID- 25867861
TI  - Dendrimer-nanoparticle conjugates in nanomedicine.
AB  - Nanomedicine can take advantage of the recent developments in nanobiotechnology
      research areas for the creation of platforms with superior drug carrier
      capabilities, selective responsiveness to the environment, unique contrast
      enhancement profiles and improved accumulation at the disease site. Colloidal
      inorganic nanoparticles (NPs) have been attracting considerable interest in
      biomedicine, from drug and gene delivery to imaging, sensing and diagnostics. It
      is essential to modify the NPs surface to have enhanced biocompatibility and
      reach multifunctional systems for the in vitro and in vivo applications,
      especially in delivering drugs locally and recognizing overexpressed
      biomolecules. This paper describes the rational design for dendrimer-nanoparticle
      conjugates elaboration and reviews their state-of-the-art uses as efficient
      nanomedicine tools. 

PMID- 25867862
TI  - Clinical applications of iron oxide nanoparticles for magnetic resonance imaging
      of brain tumors.
AB  - Current neuroimaging provides detailed anatomic and functional evaluation of
      brain tumors, allowing for improved diagnostic and prognostic capabilities. Some
      challenges persist even with today's advanced imaging techniques, including
      accurate delineation of tumor margins and distinguishing treatment effects from
      residual or recurrent tumor. Ultrasmall superparamagnetic iron oxide
      nanoparticles are an emerging tool that can add clinically useful information due
      to their distinct physiochemical features and biodistribution, while having a
      good safety profile. Nanoparticles can be used as a platform for theranostic
      drugs, which have shown great promise for the treatment of CNS malignancies. This
      review will provide an overview of clinical ultrasmall superparamagnetic iron
      oxides and how they can be applied to the diagnostic and therapeutic neuro
      oncologic setting. 

PMID- 25867863
TI  - Advances and perspectives in nanoprobes for noninvasive lymph node mapping.
AB  - Sentinel lymph node (SLN) biopsy is now being well accepted as a practical
      approach to determine axillary lymph node status. For SLN biopsy, the mapping of
      SLN is an important procedure. However, blue dyes and radioactive colloids used
      for clinical SLN mapping are associated with a few issues such as adverse side
      effects and short retention time in SLN. In recent years, nanoscale probes for
      noninvasive SLN mapping have received attention due to their adaptable synthesis
      methods, adjustable optical properties and good biocompatibility. This review
      thoroughly summarizes the design of the nanoprobes and their properties in SLN
      mapping. The aim is to understand the status of nanomaterials for SLN mapping,
      challenging work and potential clinical translation in the future. 

PMID- 25867864
TI  - Roles of Hippo signaling pathway in size control of organ regeneration.
AB  - Animals have an intrinsic regeneration ability for injured tissues and organs.
      Species that have high regeneration ability such as newts can regenerate an organ
      with exactly the same size and shape as those of the original one. It has been
      unclear how a regenerating organ grows and ceases growth at an appropriate size.
      Organ size control in regeneration is seen in various organs of various species
      that have high regeneration ability. In animal species that do not have
      sufficient regeneration ability, a wound heals (the injury is closed, but lost
      parts are not regenerated), but an organ cannot be restored to its original size.
      On the other hand, perturbation of regeneration sometimes results in oversized or
      extra structures. In this sense, organ size control plays essential roles in
      proper regeneration. In this article, we introduce the concept of size control in
      organ regeneration regulated by the Hippo signaling pathway. We focused on the
      transcriptional regulator Yap, which shuttles between the nuclei and cytoplasm to
      exert a regulatory function in a context-dependent manner. The Yap-mediated Hippo
      pathway is thought to sense cell density, extracellular matrix (ECM) contact and
      cell position and to regulate gene expression for control of organ size. This
      mechanism can reasonably explain size control of organ regeneration. 

PMID- 25867867
TI  - Intrinsic and extrinsic apoptotic pathways are involved in rat testis by cold
      water immersion-induced acute and chronic stress.
AB  - Testicular apoptosis is activated by stress, but it is not clear which signaling
      pathway is activated in response to stress. The aim of this study was to
      investigate whether intrinsic, extrinsic, or both apoptotic signaling pathways
      are activated by acute and chronic stress. Adult male rats were subjected to cold
      water immersion-induced stress for 1, 20, 40, and 50 consecutive days. The
      seminiferous tubules:apoptotic cell ratio was assayed on acute (1 day) and
      chronic (20, 40, 50 days) stress. Apoptotic markers, including cleaved-caspase 3
      and 8, the pro-apoptotic Bax and anti-apoptotic Bcl-2 proteins were also
      determined after acute and chronic stress induction. Additionally, epididymal
      sperm quality was evaluated, as well as corticosterone and testosterone levels.
      An increase in tubule apoptotic cell count percentage after an hour of acute
      stress and during chronic stress induction was observed. The apoptotic cells rate
      per tubule increment was only detected one hour after acute stress, but not with
      chronic stress. Accordingly, there was an increase in Bax, cleaved caspase-8 and
      caspase-3 pro-apoptotic proteins with a decrease of anti-apoptotic Bcl-2 in both
      acutely and chronically stressed male testes. In addition, sperm count,
      viability, as well as total and progressive motility were low in chronically
      stressed males. Finally, the levels of corticosterone increased whereas
      testosterone levels decreased in chronically stressed males. Activation of the
      extrinsic apoptotic pathway was shown by cleaved caspase-8 increase whereas the
      intrinsic apoptotic pathway activation was determined by the increase of Bax,
      along with Bcl-2 decrease, making evident a cross-talk between these two pathways
      with the activation of caspase-3. These results suggest that both acute and
      chronic stress can potentially activate the intrinsic/extrinsic apoptosis
      pathways in testes. Chronic stress also reduces the quality of epididymal
      spermatozoa, possibly due to a decrease in testosterone. 

PMID- 25867865
TI  - The effects of resistance exercise training on macro- and micro-circulatory
      responses to feeding and skeletal muscle protein anabolism in older men.
AB  - KEY POINTS: Increases in limb blood flow in response to nutrition are reduced in
      older age. Muscle microvascular blood flow (MBF) in response to nutrition is also
      reduced with advancing age and this may contribute to age-related 'anabolic
      resistance'. Resistance exercise training (RET) can rejuvenate limb blood flow
      responses to nutrition in older individuals. We report here that 20 weeks of RET
      also restores muscle MBF in older individuals. Restoration of MBF does not,
      however, enhance muscle anabolic responses to nutrition. ABSTRACT: The anabolic
      effects of dietary protein on skeletal muscle depend on adequate skeletal muscle
      perfusion, which is impaired in older people. This study explores fed state
      muscle microvascular blood flow, protein metabolism and exercise training status
      in older men. We measured leg blood flow (LBF), muscle microvascular blood volume
      (MBV) and muscle protein turnover under post-absorptive and fed state (i.v.
      Glamin to double amino acids, dextrose to sustain glucose ~7-7.5 mmol l(-1) )
      conditions in two groups: 10 untrained men (72.3 +/- 1.4 years; body mass index
      (BMI) 26.5 +/- 1.15 kg m(2) ) and 10 men who had undertaken 20 weeks of fully
      supervised, whole-body resistance exercise training (RET) (72.8 +/- 1.4 years;
      BMI 26.3 +/- 1.2 kg m(2) ). We measured LBF by Doppler ultrasound and muscle MBV
      by contrast-enhanced ultrasound. Muscle protein synthesis (MPS) was measured
      using [1, 2-(13) C2 ] leucine with breakdown (MPB) and net protein balance (NPB)
      by ring-[D5 ] phenylalanine tracers. Plasma insulin was measured via ELISA and
      indices of anabolic signalling (e.g. Akt/mTORC1) by immunoblotting from muscle
      biopsies. Whereas older untrained men did not exhibit fed-state increases in LBF
      or MBV, the RET group exhibited increases in both LBF and MBV. Despite our
      hypothesis that enhanced fed-state circulatory responses would improve anabolic
      responses to nutrition, fed-state increases in MPS (~50-75%; P < 0.001) were
      identical in both groups. Finally, whereas only the RET group exhibited fed-state
      suppression of MPB (~-38%; P < 0.05), positive NPB achieved was similar in both
      groups. We conclude that RET enhances fed-state LBF and MBV and restores nutrient
      dependent attenuation of MPB without robustly enhancing MPS or NPB.

PMID- 25867866
TI  - Toxicity profile and treatment delays in NOPHO ALL2008-comparing adults and
      children with Philadelphia chromosome-negative acute lymphoblastic leukemia.
AB  - OBJECTIVES: Cure rates improve when adolescents and young adults with acute
      lymphoblastic leukemia (ALL) are treated according to pediatric protocols.
      Assumed risks of toxicities and associated delays in treatment have played a role
      in setting upper age limits. The aim of this study was to examine the toxicity
      profile and treatment delays in NOPHO ALL2008 comparing children and adults.
      METHODS: We collected information on 19 treatment-related toxicities,
      systematically captured at 3-month intervals throughout therapy, and time
      intervals between 12 consecutive treatment phases for 1076 patients aged 1-45 yrs
      treated according to the Nordic/Baltic ALL2008 protocol. RESULTS: No adults died
      during induction. The duration of induction therapy and postinduction treatment
      phases did not differ between children and adults, except for patients 18-45 yrs
      being significantly delayed during two of nine high-risk blocks (median number of
      days for patients 1-9, 10-17, and 18-45 yrs; the
      glucocorticosteroid/antimetabolite-based block B1: 24, 26, and 29 d,
      respectively, P = 0.001, and Block 5 (in most cases also a B block): 29, 29, and
      37 d, respectively, P = 0.02). A higher incidence of thrombosis with increasing
      age was found; highest odds ratio 5.4 (95% CI: (2.6;11.0)) for patients 15-17 yrs
      compared with children 1-9 yrs (P < 0.0001). Risk of avascular osteonecrosis was
      related to age with the highest OR for patients 10-14 yrs (OR = 10.4 (95% CI:
      (4.4;24.9)), P < 0.0001). CONCLUSION: Adults followed and tolerated the NOPHO
      ALL2008 protocol virtually as well as children, although thrombosis and avascular
      osteonecrosis was most common among adolescents.

PMID- 25867868
TI  - Maximizing value in opioid utilization: Is oxycodone immediate release a good
      option for pain management?
AB  - The modern approach to the management of pain involves optimizing all aspects of
      the process. This includes utilization of pharmacologic and non-pharmacologic
      modalities, consideration of patient characteristics, proper matching of the
      physiology of the pain with the analgesic's mechanism of action
      (pharmacodynamics, PD), and the onset and duration of action (pharmacokinetics,
      PK). No single agent or formulation satisfies all of the requirements for all
      patients. Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) are
      effective options for inflammatory pain and, as is acetaminophen, for mild pain.
      Specialized agents are helpful for particular pains, such as for migraine
      headache. Opioids remain the standard option for severe pain. Although they are
      generally a safe and effective option, opioids can produce dose-limiting adverse
      effects and have abuse potential. The goal of pain therapy is thus to achieve the
      maximum pain relief with the least amount of opioid exposure. Against this
      background of measured approach to the use of analgesics, an immediate release
      (IR) oral formulation of the established opioid oxycodone has been developed to
      provide rapid onset of action and rate of titration, both of which could maximize
      temporal matching of dose with pain level and reduce total exposure to drug. This
      article considers the option of an immediate release (IR) oral formulation for
      the management of pain. 

PMID- 25867869
TI  - [The evaluation of the symptom clusters in patients with the diagnosis of
      terminal stage cancer].
AB  - OBJECTIVES: Palliative care has been developing rapidly throughout the world. A
      substantial number of palliative care patients are advanced cancer patients.
      Terminal cancer patients suffer from groups of symptoms called symptom clusters,
      rather than from individual independent symptoms. The aim of this study is to
      evaluate the symptoms of terminal cancer patients retrospectively and to present
      the symptom clusters of these patients. METHODS: After ethical approval was
      obtained, a total of 113 (74 female, 39 male) patients with the diagnosis of the
      terminal stage cancer were retrospectively evaluated in Gaziosmanpasa University,
      Department of Anesthesiology and Reanimation between January 2011 and January
      2013. Patient records were used to obtain medical history, physical examination
      findings, patient complaints, accompanying persons, primary cancer site, and
      metastasis sites. Symptoms such as fatigue, pain, vomiting, loss of
      appetite,insomnia, constipation, cough and dyspnea were assessed with the
      Edmonton Symptom Assessment System scale (0: None, 10: Worst possible). The
      symptom clusters were constructed using hierarchical symptom cluster analysis.
      RESULTS: The mean age was 64.51 +/- 11.38 years. Patients were referred to our
      outpatient clinic from Departments of General Surgery, Emergency Medicine,
      Urology, Oncology, Ear-Nose-Throat, Thoracic Surgery, Internal Medicine and
      Neurosurgery. Fatigue was the most-detected symptom (98.2%). Three symptom
      clusters were identified: nausea-vomiting-loss of appetite-constipation, dyspnea
      cough, and fatigue-pain-insomnia. CONCLUSION: Although palliative cancer patients
      were referred mainly with the symptom of pain, at least three symptom clusters
      were detected. The management of terminal stage cancer patients should focus on
      symptom clusters rather than individual symptoms.

PMID- 25867870
TI  - [Investigation of obsessive-compulsive symptoms in patients with migraine].
AB  - OBJECTIVES: A migraine is not just a headache. Migraines are characterized by the
      co-occurrence of various systemic changes and known to be associated with many
      psychiatric disorders in the interictal period, especially major depression and
      anxiety disorders. Obsessive-compulsive disorder (OCD) in patients with migraines
      is relatively less studied. METHODS: Obsessive-compulsive symptoms were
      investigated in consecutive patients with a diagnosis of migraine and compared
      with that of a control group of healthy individuals. The relationship of these
      symptoms with the defined clinical features of migraine was analyzed. 74 patients
      and 36 controls were included in this study. Patients were chosen from those
      admitted with headache complaints to the Istanbul University, Istanbul Faculty of
      Medicine, Department of Neurology, Headache Outpatient Clinics between December
      2010-March 2012. A headache specialist diagnosed all patients with migraine using
      the International Headache Society criteria.. The Yale Brown Obsessive and
      Compulsive Scale (Y-BOCS) was used to score OCD symptoms in all participants.
      RESULTS: In comparing Y-BOCS total scores between the migraine patients and the
      control group, we found a statistically significant difference (z(109)= -3.100,
      p<0.05). Furthermore, both the Y-BOCS obsession and compulsion sub-scores were
      significantly different between the groups. The duration, frequency and side of
      migraine did not have any correlation with our findings. CONCLUSION: In
      conclusion, our study suggested that migraine sufferers tend to have higher
      obsessive and compulsive symptoms. These findings could be based on genetic
      changes and/or functional differences in the brain.

PMID- 25867871
TI  - [Analgesic step ladder treatment in cancer patients with pain].
AB  - OBJECTIVES: In this study, we retrospectively evaluated the characteristics of
      1736 patients presenting to our clinic, including analgesic step treatments and
      method of treatments. METHODS: A total of 1467 patients, excluding 269 out of
      1736, with pain due to malignancy were included in this study. Patients presented
      to the Algology Division of the Department of Anesthesiology and Reanimation of
      Firat University School of Medicine. Among the patients included in the study,
      85.5% were treated according to the analgesic step ladder protocol of the WHO.
      Minimally invasive analgesic interventions were applied in 14.5% of the cases in
      which adequate pain control could not be achieved with step ladder treatment.
      RESULTS: The adjuvant pain medications used were antidepressants,
      corticosteroids, anticonvulsants, neuroleptics, benzodiazepines, local
      anesthetics, bisphosphonates, and calcitonin and their rate of usage were 61.0%,
      7.1%, 4.0%, 4.0%, 1.6%,12.3%,1.2%, and 2.8%, respectively. CONCLUSION: Because
      pain in the cancer patients is mostly severe, pain management can be difficult in
      these patients. The patients who cannot be treated with the analgesic step ladder
      method have been treated with minimally invasive analgesic intervention methods.
      A multidisciplinary medical expert group evaluation of the cases and a treatment
      planned by this team are cornerstones of achieving success in pain management. We
      believe in this way, no patient with cancer will live with uncontrolled pain.
      Access to adjuvant drugs should be easy in order to achieve success in pain
      management. We believe that expert algology physicians who treat pain should
      easily prescribe adjuvant drugs.

PMID- 25867872
TI  - Chronic pain, depression symptoms and daily living independency level among
      geriatrics in nursing home.
AB  - OBJECTIVES: The aim of this study was to investigate pain, depression and
      independence in activities of daily living in geriatric residents of nursing
      homes, as well as to evaluate the relationship between these parameters. METHODS:
      186 nursing home residents, aged 65 to 90 years, were enrolled in the study.
      Their socio-demographic features, depression levels, pain levels and independence
      in activities of daily living were evaluated using a socio-demographic assessment
      form, the Geriatric Depression Scale (GDS), the Visual Analogue Scale (VAS) and
      the Nottingham Extended Activities of Daily Living Index (NEADL), respectively.
      For statistical analyses, participants were divided into groups with and without
      chronic pain. RESULTS: The main finding of this study was that 55.9% of the
      participants reported chronic pain, and these participants had significantly
      higher GDS (p=0.001) and lower NEADL scores (p=0.01) than those who reported no
      chronic pain. We found a significant correlation between VAS and GDS (r=0.47,
      p=0.001), VAS and NEADL (r=-0.30, p=0.001), and GDS and NEADL scores (r=-0.50,
      p=0.001). Female gender (p=0.001), number of children (p=0.005), number of
      chronic diseases (p=0.009), and GDS score (p=0.001) were found to affect chronic
      pain in multivariate model. CONCLUSION: Investigation of pain, presence of
      depression, and independence in activities of daily living is important in
      determining the necessary measures to be adopted for promoting the health and
      well-being of the geriatric population.

PMID- 25867873
TI  - Treatment of compensatory hyperhidrosis of the trunk with radiofrequency
      ablation.
AB  - OBJECTIVES: Although Endoscopic Thoracic Sympathectomy is a widely accepted
      treatment method for patients with palmar hyperhidrosis, compensatory
      hyperhidrosis of the trunk remains a challenging side effect of the procedure. No
      satisfactory treatment options for this side effect were available until now. In
      this study, we aimed to define a new procedure for the treatment of compensatory
      hyperhidrosis of the trunk. METHODS: A total of 10 patients admitted our
      institution for the treatment of compensatory hyperhidrosis of the trunk were
      enrolled in the study between November 2010 and January 2012 in a prospective
      manner. Sympathetic blockage was achieved via radiofrequency thermo-ablation
      technique. The results of treatment were evaluated via telephone calls. RESULTS:
      Ten patients (2 females, 8 males) underwent radiofrequency thermo-ablation of T6
      sympathetic ganglion for compensatory hyperhidrosis of the trunk. The mean age
      was 29.2 years and the median duration of symptom was 10.5 months. The median
      follow-up period was 14 months. Six of ten patients (60%) were treated
      successfully. There was no procedure related complication. CONCLUSION: The
      radiofrequency treatment for patients with compensatory hyperhidrosis of the
      trunk is an alternative option with promising results.

PMID- 25867874
TI  - Does perioperative opioid infusion increase postoperative opioid requirement?
AB  - OBJECTIVES: Opioids are the cornerstone therapy for the optimal pain management.
      Perioperative opioid infusion is accused of causing acute opioid tolerance,
      especially as the postoperative opioid requirement increases in time to provide
      efficient analgesia. It is debatable whether there is a difference between opioid
      agents regarding tolerance development. We aim to compare the effects of
      morphine, remifentanil and alfentanil when infused intravenously during the
      perioperative period. METHODS: Sixty patients undergoing elective major abdominal
      surgery were randomized into four groups. The four groups obtained the following
      treatments: saline 5 cc iv bolus and 10 cc/h infusion for induction and
      maintenance in Group C, remifentanil infusion 0.25 ug/kg/min following 1 ug/kg iv
      bolus in Group R, alfentanil infusion 0.50 ug/kg/min following 10 ug/kg iv bolus
      in Group A, and morphine infusion 0.02 mg/kg/h after 0.1 mg/kg iv bolus in Group
      M. Meperidine 10 mg/cc iv patient-controlled analgesia was used postoperatively,
      and total meperidine consumptions were recorded. VAS scores and side effects were
      recorded during postoperative 48 hours. RESULTS: VAS scores in Group M were found
      to be significantly lower than in Group C at the 1st postoperative hour. Twenty
      four hour total meperidine consumption in Group R and Group M were significantly
      lower than in Group C. No statistical difference was found between groups
      regarding the incidence of nausea and vomiting. CONCLUSION: Our study indicated
      that infusions of morphine, alfentanil and remifentanil administered to patients
      undergoing major abdominal surgery did not cause acute opioid tolerance. In
      contrast, infusion of morphine and remifentanil reduced postoperative opioid
      requirement.

PMID- 25867875
TI  - Sudden developing convulsion during interscalene block: Does propofol anesthesia
      diminish plasma bupivacaine level?
AB  - We aim to review local anesthetic systemic toxicity (LAST) due to suddenly
      developing convulsion during interscalene block in a 67-year-old patient
      undergoing shoulder surgery.

PMID- 25867876
TI  - [Transient spinal myoclonus due to epidural levobupivacaine infusion: case
      report].
AB  - Spinal myoclonus following regional anaesthesia is extremely rare. We report a
      patient who developed spinal myoclonus after an epidural infusion of
      levobupivacaine. 

PMID- 25867877
TI  - [Displacement to epidural catheter].

PMID- 25867879
TI  - The "T" in JOPT.

PMID- 25867880
TI  - Eyes on new product development.

PMID- 25867881
TI  - Seven-day mortality can be predicted in medical patients by blood pressure, age,
      respiratory rate, loss of independence, and peripheral oxygen saturation (the
      PARIS score): a prospective cohort study with external validation.
AB  - BACKGROUND: Most existing risk stratification systems predicting mortality in
      emergency departments or admission units are complex in clinical use or have not
      been validated to a level where use is considered appropriate. We aimed to
      develop and validate a simple system that predicts seven-day mortality of acutely
      admitted medical patients using routinely collected variables obtained within the
      first minutes after arrival. METHODS AND FINDINGS: This observational prospective
      cohort study used three independent cohorts at the medical admission units at a
      regional teaching hospital and a tertiary university hospital and included all
      adult (>= 15 years) patients. Multivariable logistic regression analysis was used
      to identify the clinical variables that best predicted the endpoint. From this,
      we developed a simplified model that can be calculated without specialized tools
      or loss of predictive ability. The outcome was defined as seven-day all-cause
      mortality. 76 patients (2.5%) met the endpoint in the development cohort, 57
      (2.0%) in the first validation cohort, and 111 (4.3%) in the second. Systolic
      blood Pressure, Age, Respiratory rate, loss of Independence, and peripheral
      oxygen Saturation were associated with the endpoint (full model). Based on this,
      we developed a simple score (range 0-5), ie, the PARIS score, by dichotomizing
      the variables. The ability to identify patients at increased risk (discriminatory
      power and calibration) was excellent for all three cohorts using both models. For
      patients with a PARIS score >= 3, sensitivity was 62.5-74.0%, specificity 85.9
      91.1%, positive predictive value 11.2-17.5%, and negative predictive value 98.3
      99.3%. Patients with a score <= 1 had a low mortality (<= 1%); with 2,
      intermediate mortality (2-5%); and >= 3, high mortality (>= 10%). CONCLUSIONS:
      Seven-day mortality can be predicted upon admission with high sensitivity and
      specificity and excellent negative predictive values.

PMID- 25867882
TI  - Upright imaging of Drosophila egg chambers.
AB  - Drosophila melanogaster oogenesis provides an ideal context for studying varied
      developmental processes since the ovary is relatively simple in architecture, is
      well-characterized, and is amenable to genetic analysis. Each egg chamber
      consists of germ-line cells surrounded by a single epithelial layer of somatic
      follicle cells. Subsets of follicle cells undergo differentiation during specific
      stages to become several different cell types. Standard techniques primarily
      allow for a lateral view of egg chambers, and therefore a limited view of
      follicle cell organization and identity. The upright imaging protocol describes a
      mounting technique that enables a novel, vertical view of egg chambers with a
      standard confocal microscope. Samples are first mounted between two layers of
      glycerin jelly in a lateral (horizontal) position on a glass microscope slide.
      The jelly with encased egg chambers is then cut into blocks, transferred to a
      coverslip, and flipped to position egg chambers upright. Mounted egg chambers can
      be imaged on either an upright or an inverted confocal microscope. This technique
      enables the study of follicle cell specification, organization, molecular
      markers, and egg development with new detail and from a new perspective. 

PMID- 25867883
TI  - Vigorous-intensity physical activity is associated with metabolic syndrome among
      the Chinese middle-aged population: a cross-sectional study.
AB  - OBJECTIVE: To examine the association and relative contribution of different
      levels of physical activity (PA) with metabolic syndrome (MS). METHODS: The
      cluster sampling method was used to recruit 8,750 community-based individuals
      between 40 and 60 years of age. MS was defined according to the International
      Diabetes Federation, 2005. PA was estimated with the International Physical
      Activity Questionnaire, and three levels of PA (low, moderate, vigorous) were
      used to classify the individuals. The risk factors of MS were comprehensively
      collected, and logistic regression methods were used to measure the association
      between PA and MS. Population-attributable risks and their 95% confidence
      intervals (CI) were calculated based on the regression model. RESULTS:
      Approximately 30.4% (2,661) of the participants were MS patients. The percentage
      of individuals with vigorous levels of PA was 46.2% and 43.5% and with low levels
      of PA was 11.3% and 11.3% in non-MS and MS group, respectively. Individuals with
      vigorous PA had an odds ratio (OR) of 0.78 (95% CI: 0.66, 0.91) for MS compared
      with those with low PA, and the OR for individuals with moderate PA was 0.85 (95%
      CI: 0.73, 1.01). Moderate and vigorous PA levels decreased risk of MS by 18.3%,
      with approximately 11% of that decrease due to vigorous PA. CONCLUSIONS: Vigorous
      PA levels were consistently associated with a reduced risk of MS; however, a
      protective role of moderate PA was not found. The population-attributable risk
      for vigorous PA was about 11% for all MS risk factors.

PMID- 25867884
TI  - [MAM-E17 schizophrenia rat model].
AB  - Schizophrenia is a serious neuropsychiatric disorder. Several brain structures,
      neurotransmitter systems, genetic and environmental risk factors are suspected in
      the background. Because of its complexity the mechanism of the disorder is not
      known exactly, so the treatment of patients is unsolved. In the research of
      schizophrenia application of the rodent models is widespread. In this study one
      of these models based on the effect of methylazoxymethanol- acetate (MAM) is
      described, which is a neurodevelopmental, validated rat model. This antimitotic
      agent is able to evoke a number of schizophrenic symptomes temporarily disrupting
      the prenatal neurogenesis. The model reproduces numerous histological and
      neurophysiological changes of the human disorder, moreover it also represents
      several behavioral and cognitive phenomena resembling those in schizophrenia. A
      salient advantage of the model is the demonstration of the diachronic feature of
      the disorder, that is, postpubertal appearance of the positive symptoms. This
      model provides widespread opportunities for manipulations of the symptoms, so
      that using it in the future investigations can lead to a better understanding of
      this disorder. 

PMID- 25867885
TI  - Treatment adherence and insight in schizophrenia.
AB  - BACKGROUND: Lack of adherence to treatment in patients with schizophrenia is a
      major risk factor for poor outcome, including relapse, rehospitalization, and
      suicide. Poor insight into illness may be a leading cause for partial- or
      nonadherence since a high proportion of patients with schizophrenia are partially
      or completely unaware of their mental disorder. OBJECTIVE: The primary objective
      was to estimate the impact of lack of insight on adherence to medication based on
      a population of patients in Hungary who had the diagnosis of schizophrenia. The
      secondary objective was to investigate the association of the different aspects
      of insight (awareness of illness, the capacity to relabel psychotic experiences
      as abnormal, treatment acceptance) with (1) recent adherence behavior; (2)
      current mental state; (3) remission/non-remission status as measured by remission
      severity criteria; and (4) demographic and treatment history data. METHOD: This
      was cross-sectional, noninterventional study, carried out under daily clinical
      practice conditions, with no influence exerted upon clinical practice in view of
      the observational nature of the study. Eligibility criteria included: a)
      patients' age (>18 years), b) diagnosis of schizophrenia (ICD-10), c) signed
      informed consent, d) no concomitant participation in another clinical trial.
      Study sites represented Mental Health Centers and outpatient clinics of hospital
      psychiatric units. Each investigator was asked to enroll patients consecutively.
      The final analysis sample comprised 262 patients, distributed across 13 sites.
      The following data were collected: general sociodemographic and clinical data
      (age, sex, level of education, socioeconomic situation, family support,
      psychiatric diagnosis, years of evolution, pharmacological and/or psychosocial
      treatments at the time of inclusion in the study, previous psychiatric
      admissions), with assessments of the Schedule of Assessing components of Insight
      (SAI), Compliance Rating Scale (CRS), Clinical Global Impression Scale (CGI-S),
      Remission Severity Criteria. RESULTS: Patients enrolled in the study had a mean
      (SD) age of 43.0 (12.6) years, with a 12.3 (3.0) years of education, and
      approximately evenly balanced gender distribution. According to the clinical
      judgment of the treating physicians, 29.1% of the patients were not taking their
      prescribed antipsychotic medication in our target population. The primary
      logistic regression analysis indicated a significant relationship between the
      total score on the SAI scale and the Compliance Scale (Spearman correlation=0.58;
      p<0.0001). The relationship was significant for each of the three subscales of
      SAI. Secondary analyses showed a significant negative association between
      compliance and score on the CGI-S scale (Spearman correlation: -0.54; p<0.0001),
      and compliance and hostility, as measured by the PANSS hostility item (Spearman
      correlation: -0.40; p<0.0001). We found no significant relationship between
      compliance and age, gender or education years (p>0.1 in all cases). CONCLUSIONS:
      The results of the present study support the hypothesis that the level of insight
      and compliance are strongly associated, and that more severe symptoms and
      increasing levels of hostility, in particular, markedly reduce the compliance of
      the patients with schizophrenia. Capturing different aspects of insight may be
      helpful in understanding and improving adherence behavior in clinical practice.

PMID- 25867886
TI  - [Current issues in psychiatric ethics].
AB  - The article analyzes some ethical problems in psychiatry that have been emerging
      in recent years. It deals with the ongoing intensive debates about the DSM-5
      before its publication, and with some of the criticisms of the DSM-5 itself. Then
      it goes on to analyze the use of placebo. This is followed by the ethical
      problems of the treatment of ADHD with stimulant drugs, among which one is the
      question of authenticity, namely whether the pre-treatment or the post-treatment
      personality is the real, authentic self of the patient. This question has been
      raised not only in the case of the ADHD, but also in relation with the
      antidepressant treatment of depression earlier, and in relation with deep brain
      stimulation and dopamine replacement therapy now, all of which causes changes in
      the treated patient's personality and motivations. Finally the article describes
      some ethical problems of informed consent in the case of antidepressant
      medication, together with the necessity to involve psychiatric nurses and rating
      scales in the assessment of the patient's decision making capacity.

PMID- 25867887
TI  - [The role of playful interactions in the development of the early mother-child
      relationship--factors of risk and protection].
AB  - BACKGROUND AND AIMS: The early mother-child relationship is taking shape and
      evolving during the series of their everyday interactions. The main aim of the
      research that focus on the risks at the beginning, and the future mother infant
      interactions are factors that have influence on the quality of the early mother
      child relationship, and the exploration of the jeopardy and vulnerability of the
      early relationship disorders. METHODS: I examined fifty mothers who have their
      first child. I researched the motherly, child- and interactional factors in the
      days right after the birth and then when the kids were one month old, and again
      at the age of four and a half month. I assessed the parental stress by the longer
      version of the PSI (Parenting Stress Index), and the mother anxiety with the help
      of the STAI-Y (State and feature anxiety value Index), and the features of the
      depression were tested by the EPDS scale, the Edinburgh Post-natal Depression
      Scale. PBQ, the Postpartum Bonding Questionnare--reveals the quality of the
      motherly emotions and behaviour focusing on the kid. The observation of
      interactions when the child was four and a half month old happened while a 'face
      to-face' free play, and the analyses of that were assessed by an own code system.
      RESULTS: We found correlations between input risk factors and features of
      motherly interactional styles. The indexes of the after birth depression
      (depression right after the birth), and the anxiety also showed correlation to
      the indexes of the attachment of the mother to her child and the parental stress.
      The correlations among the playfulness, the risk kotodefactors and the quality of
      the interactions are obvious, that we found. The interactional style of the
      mother and the interactional strategies of the baby showed correlated patterns
      too as we examined those. CONCLUSIONS/IMPLICATIONS: We found that pre-history of
      pregnancy and perinatal events have predictive value on the relationship of the
      four and a half month old baby and his/her mother. These can add important facts
      to the prevention and early-prevention of the early mother-child interactions,
      and other factors in cognition of the potential strengths and weaknesses in order
      to prevent the future negative outputs (attachment, cognitive and social
      emotional development, emotional and behavioural disorders).

PMID- 25867888
TI  - [Impact of depressive symptomatology in Hungarian infertile couples].
AB  - INTRODUCTION: Involuntary childnessness is a paranormative crisis for couples who
      react with depressive and anxious symptoms to infertility. Depressive symptoms
      correlate with infertility-related distress and fertility specific quality of
      life. At the same time, depression effects not only the personal, but also the
      partner's psychological adjustment. In our study, we investigate the incidence
      rate of depressive symptomatology and correlations between severity of depression
      and infertility-related distress in Hungarian couples. METHODS: We recruited 126
      couples attending the first infertility consultation who filled in Fertility
      Problem Inventory (FPI), shortened version of Beck Depression Inventory (BDI) and
      answered sociodemographic questions. In statistical analyses, logistic regression
      analysis and multivariate analysis of variance were performed. RESULTS: Mild
      depressive symptoms were more frequent in the infertile sample compared to
      general population (OR=0.43, 95% CI: 0.20-0.92, p<0.05). In women, there were
      more mild (OR: 1.97, 95% CI 1.07-3.60, p<0.05) and severe depressive symptoms
      (OR: 2.46, 95% CI 1.21-5.00, p<0.05), than in men. In women, only severe
      depression made a difference in fertility specific distress; in men both mild and
      severe depressive symptoms correlated with more concerns (all ps<0.001). Being
      depressed correlated with partner's depression (all ps<0.05). If the partner had
      more severe depressive symptoms, it increased one's infertility-related
      relational concerns (all ps<0.01). Men reported more sexual concerns when female
      partner had mild level of depression (F(2)=3.29, p<0.05). CONCLUSION: Our results
      provide important information for reproductive medical staff. Our findings
      emphasize that women and men could have depressive symptoms already at the
      beginning of assisted reproductive treatments and that depression effects on
      infertility-related distress on personal and partner levels.

PMID- 25867889
TI  - [Prevalence of psychiatric disorders in homeless population].
AB  - BACKGROUND: Prevalence of psychiatric disorders in homeless population is high
      and it can increase the risk of criminal behavior. In Hungary no systematic study
      was performed in this field until this time. This study aimed to survey the
      prevalence rate of psychiatric disorders among people living in homeless shelters
      and explore its correlations with demographic variables. Investigating the
      correlation between psychiatric disorders and criminal behavior was also among
      the aims of the study. METHODS: Data concerning medical and forensic history was
      collected in a structured interview and then SCID-I and SCID-II diagnostic
      interview was performed in voluntary persons living in 3 homeless shelters.
      RESULTS: Eighty-six percent of the sample had a diagnosable psychiatric disorder.
      Personality disorder and alcohol dependence were the most common diagnoses in
      males, while personality disorder and anxiety disorders were the most common
      diagnoses in females. Comorbid conditions were present in 72% of the cases. Only
      37% of those who had a DSM diagnosis were currently in psychiatric care. The
      lowest rate was found in patients with major depression (31%). Only drug and
      psychopharmacon dependence showed significant correlation (p=0.023 and p=0.024)
      with violent and non-violent offending out of the diagnostic subgroups.
      CONCLUSIONS: Prevalence of severe mental disorders among homeless persons is high
      in Hungary too. Low rate of homeless persons being in psychiatric care indicates
      that traditional structure of care is not suitable for them, they need a tailored
      complex approach. This survey confirmed that criminal behavior is not more
      frequent among those homeless persons who have psychiatric disorders neither in
      terms of violent nor in non-violent acts except those having drug or
      psychopharmacon dependence.

PMID- 25867890
TI  - [Cognitive conceptualization of adult attention deficit hyperactivity disorder: a
      systematic review].
AB  - AIMS: Attention deficit hyperactivity disorder (ADHD) is one of the most
      prevalent chronic neuropsychiatric disorders continuing from childhood into
      adulthood in 40-66% of cases. Though genetic underpinnings of the disorder are
      unquestionable, previous research underlie the fact that children with ADHD are
      faced with more adversities which might lead to maladaptive beliefs about self
      and world. Our aim was to provide a systematic review of ADHD studies focusing on
      cognitive conceptualization of the disorder. METHODS: A systematic literature
      search was conducted in three databases (PsychINFO, MEDLINE and Scopus) between
      years 2000 and 2013 with the keywords "ADHD, attention deficit hyperactivity
      disorder" and "core beliefs, belief system, schemas, schema therapy,
      dysfunctional attitude, compensatory strategies, negative automatic thoughts,
      case conceptualization". RESULTS: We were able to identify ten original papers.
      According to them, adult ADHD could be characterized by maladaptive schemata
      including failure, impaired self-control, being different from others and a sense
      of inadequacy. Dysfunctional attitudes in adult ADHD were related to comorbid
      mood disorders. Compensatory strategies, e.g. anticipatory avoidance,
      brinkmanship, juggling, pseudo efficiency were described. More negative automatic
      thoughts were found in adult patients with ADHD, especially with comorbid mood
      disorder. Cognitive distortions, such as overgeneralization, magical and
      comparative thinking were also reported. CONCLUSIONS: Though more empirical
      research is needed, converging results were reviewed about the cognitive
      characteristics of adult ADHD. Cognitive behavior therapy was showed to be
      effective in treatment of adult ADHD; the improvement of our knowledge about
      cognitive conceptualization of the disorder is a very important challenge for
      further research.

PMID- 25867891
TI  - [Time out of joint -- the experience of temporality in poetry and psychiatry].

PMID- 25867892
TI  - Culture and co-culture of mouse ovaries and ovarian follicles.
AB  - The mammalian ovary is composed of ovarian follicles, each follicle consisting of
      a single oocyte surrounded by somatic granulosa cells, enclosed together within a
      basement membrane. A finite pool of follicles is laid down during embryonic
      development, when oocytes in meiotic arrest form a close association with
      flattened granulosa cells, forming primordial follicles. By or shortly after
      birth, mammalian ovaries contain their lifetime's supply of primordial follicles,
      from which point onwards there is a steady release of follicles into the growing
      follicular pool. The ovary is particularly amenable to development in vitro, with
      follicles growing in a highly physiological manner in culture. This work
      describes the culture of whole neonatal ovaries containing primordial follicles,
      and the culture of individual ovarian follicles, a method which can support the
      development of follicles from an immature through to the preovulatory stage,
      after which their oocytes are able to undergo fertilization in vitro. The work
      outlined here uses culture systems to determine how the ovary is affected by
      exposure to external compounds. We also describe a co-culture system, which
      allows investigation of the interactions that occur between growing follicles and
      the non-growing pool of primordial follicles. 

PMID- 25867894
TI  - Dissolution chemistry and biocompatibility of silicon- and germanium-based
      semiconductors for transient electronics.
AB  - Semiconducting materials are central to the development of high-performance
      electronics that are capable of dissolving completely when immersed in aqueous
      solutions, groundwater, or biofluids, for applications in temporary biomedical
      implants, environmentally degradable sensors, and other systems. The results
      reported here include comprehensive studies of the dissolution by hydrolysis of
      polycrystalline silicon, amorphous silicon, silicon-germanium, and germanium in
      aqueous solutions of various pH values and temperatures. In vitro cellular
      toxicity evaluations demonstrate the biocompatibility of the materials and end
      products of dissolution, thereby supporting their potential for use in
      biodegradable electronics. A fully dissolvable thin-film solar cell illustrates
      the ability to integrate these semiconductors into functional systems. 

PMID- 25867893
TI  - Experimental subarachnoid hemorrhage in rats: comparison of two endovascular
      perforation techniques with respect to success rate, confounding pathologies and
      early hippocampal tissue lesion pattern.
AB  - Recently aside from the "classic" endovascular monofilament perforation technique
      to induce experimental subarachnoid hemorrhage (SAH) a modification using a
      tungsten wire advanced through a guide tube has been described. We aim to assess
      both techniques for their success rate (induction of SAH without confounding
      pathologies) as primary endpoint. Further, the early tissue lesion pattern as
      evidence for early brain injury will be analyzed as secondary endpoint. Sprague
      Dawley rats (n=39) were randomly assigned to receive either Sham surgery (n=4),
      SAH using the "classic" technique (n=18) or using a modified technique (n=17).
      Course of intracranial pressure (ICP) and regional cerebral blood flow (rCBF) was
      analyzed; subsequent pathologies were documented either 6 or 24 h after SAH.
      Hippocampal tissue samples were analyzed via immunohistochemistry and western
      blotting. SAH-induction, regardless of confounding pathologies, was independent
      from type of technique (p=0.679). There was no significant difference concerning
      case fatality rate (classic: 40%; modified: 20%; p=0.213). Successful induction
      of SAH without collateral ICH or SDH was possible in 40% with the classic and in
      86.7% with the modified technique (p=0.008). Peak ICP levels differed
      significantly between the two groups (classic: 94 +/- 23 mmHg; modified: 68 +/-
      19 mmHg; p=0.003). Evidence of early cellular stress response and activation of
      apoptotic pathways 6 h after SAH was demonstrated. The extent of stress response
      is not dependent on type of technique. Both tested techniques successfully
      produce SAH including activation of an early stress response and apoptotic
      pathways in the hippocampal tissue. However, the induction of SAH with less
      confounding pathologies was more frequently achieved with the modified tungsten
      wire technique. 

PMID- 25867895
TI  - Metabolite profiling of barley grain subjected to induced drought stress:
      responses of free amino acids in differently adapted cultivars.
AB  - To investigate cultivar-specific metabolite changes upon drought stress in barley
      grain, differently adapted cultivars were field-grown under drought conditions
      using a rain-out shelter and under normal weather conditions (2010-2012). The
      grain was subjected to a gas chromatography-mass spectrometry-based metabolite
      profiling approach allowing the analyses of a broad spectrum of lipophilic and
      hydrophilic low molecular weight constituents. Multi- and univariate analyses
      demonstrated that there are grain metabolites which were significantly changed
      upon drought stress, either decreased or increased in all cultivars. On the other
      hand, for proteinogenic free amino acids increased concentrations were
      consistently observed in all seasons only in cultivars for which no drought
      resistance/tolerance had been described. Consistent decreases were seen only in
      the group of stress tolerant/resistant cultivars. These cultivar-specific
      correlations were particularly pronounced for branched-chain amino acids. The
      results indicate that free amino acids may serve as potential markers for
      cultivars differently adapted to drought stress. 

PMID- 25867896
TI  - Voltage and calcium dual channel optical mapping of cultured HL-1 atrial myocyte
      monolayer.
AB  - Optical mapping has proven to be a valuable technique to detect cardiac
      electrical activity on both intact ex vivo hearts and in cultured myocyte
      monolayers. HL-1 cells have been widely used as a 2-Dimensional cellular model
      for studying diverse aspects of cardiac physiology. However, it has been a great
      challenge to optically map calcium (Ca) transients and action potentials
      simultaneously from the same field of view in a cultured HL-1 atrial cell
      monolayer. This is because special handling and care is required to prepare
      healthy cells that can be electrically captured and optically mapped. Therefore,
      we have developed an optimal working protocol for dual channel optical mapping.
      In this manuscript, we have described in detail how to perform the dual channel
      optical mapping experiment. This protocol is a useful tool to enhance the
      understanding of action potential propagation and Ca kinetics in arrhythmia
      development. 

PMID- 25867899
TI  - Preparation and properties of aqueous castor oil-based polyurethane-silica
      nanocomposite dispersions through a sol-gel process.
AB  - Waterborne castor oil-based polyurethane-silica nanocomposites with the polymer
      matrix and silica nanoparticles chemically bonded have been successfully prepared
      through a sol-gel process. The formation of silica nanoparticles in water not
      only reinforces the resulting coatings, but also increases the crosslink density
      of the nanocomposites. The (29)Si solid state NMR spectrum indicates the
      formation of silica and the TEM indicates that the nanoparticles are embedded in
      the polymers, resembling a core-shell structure. The silica nanoparticles in the
      polymer matrix play an important role in improving both the mechanical properties
      and the thermal stabilities of the resulting nanocomposites. This work provides
      an effective and promising way to prepare biorenewable, high performance
      nanocomposite coatings.

PMID- 25867897
TI  - Overview of a surface-ripened cheese community functioning by meta-omics
      analyses.
AB  - Cheese ripening is a complex biochemical process driven by microbial communities
      composed of both eukaryotes and prokaryotes. Surface-ripened cheeses are widely
      consumed all over the world and are appreciated for their characteristic flavor.
      Microbial community composition has been studied for a long time on surface
      ripened cheeses, but only limited knowledge has been acquired about its in situ
      metabolic activities. We applied metagenomic, metatranscriptomic and biochemical
      analyses to an experimental surface-ripened cheese composed of nine microbial
      species during four weeks of ripening. By combining all of the data, we were able
      to obtain an overview of the cheese maturation process and to better understand
      the metabolic activities of the different community members and their possible
      interactions. Furthermore, differential expression analysis was used to select a
      set of biomarker genes, providing a valuable tool that can be used to monitor the
      cheese-making process. 

PMID- 25867900
TI  - Tetrazine-norbornene click reactions to functionalize degradable polymers derived
      from lactide.
AB  - Post-polymerization modification of polymers derived from sustainable resources
      using the click reaction between tetrazines and norbornenes is shown to provide a
      mild and efficient route for the synthesis of functional degradable polymers.
      Norbornene chain-end functional poly(lactide) was synthesized using
      organocatalytic methods and functionalized by the addition of 3,6-di-2-pyridyl
      1,2,4,5-tetrazine without degradation of the polymer backbone. The versatility of
      this reaction was demonstrated by the application of analogues bearing amine and
      poly(ethylene oxide) groups to realize amine-functional polymers and block
      copolymers. Poly(spiro[6-methyl-1,4-dioxane-2,5-dione-3,2'
      bicyclo[2.2.1]hept[5]ene]) was prepared from lactide. The pendant norbornene
      group on the backbone of the resultant polymer was modified in a similar manner
      to produce functional degradable polymers and graft co-polymers. 

PMID- 25867901
TI  - Genome-wide protein-protein interaction screening by protein-fragment
      complementation assay (PCA) in living cells.
AB  - Proteins are the building blocks, effectors and signal mediators of cellular
      processes. A protein's function, regulation and localization often depend on its
      interactions with other proteins. Here, we describe a protocol for the yeast
      protein-fragment complementation assay (PCA), a powerful method to detect direct
      and proximal associations between proteins in living cells. The interaction
      between two proteins, each fused to a dihydrofolate reductase (DHFR) protein
      fragment, translates into growth of yeast strains in presence of the drug
      methotrexate (MTX). Differential fitness, resulting from different amounts of
      reconstituted DHFR enzyme, can be quantified on high-density colony arrays,
      allowing to differentiate interacting from non-interacting bait-prey pairs. The
      high-throughput protocol presented here is performed using a robotic platform
      that parallelizes mating of bait and prey strains carrying complementary DHFR
      fragment fusion proteins and the survival assay on MTX. This protocol allows to
      systematically test for thousands of protein-protein interactions (PPIs)
      involving bait proteins of interest and offers several advantages over other PPI
      detection assays, including the study of proteins expressed from their endogenous
      promoters without the need for modifying protein localization and for the
      assembly of complex reporter constructs. 

PMID- 25867903
TI  - Atypical Localization of Enchondroma in the Calcaneus.
AB  - A 53-year-old man presented to the orthopedic outpatient clinic with pain and
      swelling in the right heel without any trauma. On physical examination and
      radiologic assessment, a lesion with calcification and peripheral sclerosis was
      detected in the medullary cavity of the calcaneus, and computed tomographic
      images revealed cortical thinning adjacent to the lesion. Magnetic resonance
      images showed a 23 * 19-mm lesion. Tru-Cut biopsy, performed to clarify the
      diagnosis, revealed an enchondroma. As a definitive treatment, curettage of the
      lesion and grafting of the cavity was performed. Although enchondromas are common
      pathologic abnormalities of the skeleton and are usually asymptomatic, atypical
      localization, such as the calcaneus, and atypical clinical manifestations, such
      as heel pain, should also be kept in mind.

PMID- 25867902
TI  - A dynamic view of ATP-coupled functioning cycle of Hsp90 N-terminal domain.
AB  - Heat-shock protein 90 (Hsp90) is one of the most important chaperones involved in
      multiple cellular processes. The chaperoning function of Hsp90 is intimately
      coupled to the ATPase activity presented by its N-terminal domain. However, the
      molecular mechanism for the ATP-dependent working cycle of Hsp90 is still not
      fully understood. In this study, we use NMR techniques to investigate the
      structural characteristics and dynamic behaviors of Hsp90 N-terminal domain in
      its free and AMPPCP (ATP analogue) or ADP-bound states. We demonstrated that
      although AMPPCP and ADP bind to almost the same region of Hsp90, significantly
      different effects on the dynamics behaviors of the key structural elements were
      observed. AMPPCP binding favors the formation of the active homodimer of Hsp90 by
      enhancing the slow-motion featured conformational exchanges of those residues
      (A117-A141) within the lid segment (A111-G135) and around region, while ADP
      binding keeps Hsp90 staying at the inactive state by increasing the
      conformational rigidity of the lid segment and around region. Based on our
      findings, a dynamic working model for the ATP-dependent functioning cycle of
      Hsp90 was proposed. 

PMID- 25867904
TI  - External Ventricular and Lumbar Drain Device Infections in ICU Patients: A
      Prospective Multicenter Italian Study.
AB  - OBJECTIVE: Use of external ventricular drains and lumbar catheters is associated
      with a risk of ventriculitis and meningitis ranging from 2% to 24% because of
      lack of standardized diagnostic criteria. We evaluated the prevalence of
      ventriculitis or meningitis in 13 Italian ICUs. DESIGN: Multicenter, prospective
      study. SETTING: Thirteen Italian ICUs. PATIENTS: Two hundred seventy-one patients
      (mean age, 57 yr) receiving a total number of 311 catheters. Two hundred fifty
      patients (92.2%) had an external ventricular drain, 17 patients (6.3%) had a
      lumbar catheter, and four patients (1.5%) had both external ventricular drain and
      lumbar catheter. INTERVENTIONS: ICUs enrolled at least 10 consecutive adult
      patients with an external ventricular drain or lumbar catheter in place for more
      than 24 hours. Confirmed cerebrospinal fluid infection was defined by presence of
      a positive cerebrospinal fluid culture, a cerebrospinal fluid/blood glucose ratio
      less than 0.5, a neutrophilic cerebrospinal fluid pleocytosis (> 5 cells/MUL),
      and fever. Abnormal cerebrospinal fluid findings with negative cultures were
      defined as suspected infection. MEASUREMENTS AND MAIN RESULTS: Median duration of
      device use was 13 days (interquartile range, 8-19). Fifteen patients (5.5%) had a
      confirmed ventriculitis or meningitis, and 15 patients (5.5%) had a suspected
      ventriculitis or meningitis. Cerebrospinal fluid glucose and cerebrospinal
      fluid/blood glucose ratio were lower in patients with confirmed ventriculitis or
      meningitis and suspected ventriculitis or meningitis; proteins and lactates were
      significantly higher in confirmed ventriculitis or meningitis. Gram-negative and
      Gram-positive bacteria were equally cultured. Risk factors for infection were a
      concomitant extracranial infection (odds ratio, 2.34; 95% CI, 1.01-5.40; p =
      0.05) and placement of catheters outside the operation room (odds ratio, 4.01;
      95% CI, 0.98-16.50; p = 0.05). CONCLUSIONS: Ventriculitis or meningitis remains a
      problem in Italian ICUs, and a strategy for reducing the prevalence is worth
      planning.

PMID- 25867905
TI  - Palliative Care Needs in the Neuro-ICU.
AB  - OBJECTIVES: Patients admitted to the neurological or neurosurgical ICU are likely
      to have palliative care needs. The goals of this project are to encourage the ICU
      team to identify palliative care needs for patients and their families and
      potential ways to meet those needs. DESIGN: Quality improvement project using a
      parallel-group prospective cohort design. SETTING: Single neuro-ICU at a large,
      academic medical center. PATIENTS: All patients admitted to the neuro-ICU from
      September 1, 2013, to November 30, 2013. INTERVENTIONS: We developed a palliative
      care needs screening tool consisting of four questions: 1) Does the patient have
      distressing physical or psychological symptoms? 2) Are there specific support
      needs for patient or family? 3) Are treatment options matched with patient
      centered goals? 4) Are there disagreements among teams and family? We implemented
      this daily screening tool on morning rounds for one of two neurocritical care
      services that alternate admitting days to a single neuro-ICU. We examined
      prevalence and nature of palliative care needs and actions to address those
      needs, comparing the services with and without screening. MEASUREMENTS AND MAIN
      RESULTS: Over the 3-month period, 130 patients were admitted to the service with
      screening and 132 patients to the service without screening. The two groups did
      not differ with regard to age, gender, Glasgow Coma Scale, or diagnosis.
      Palliative care needs were identified in 62% of screened patients (80/130). Needs
      were mainly social support (53%) and establishing goals of care (28%). Screening
      was associated with more documented family conferences (p = 0.019) and a trend
      toward more palliative care consultations (p = 0.056). CONCLUSIONS: We developed
      a brief palliative care needs screening tool that identified palliative care
      needs for 62% neuro-ICU patients. This tool was associated with actions to meet
      these needs, potentially improving care for patients and their families.

PMID- 25867906
TI  - An Electronic Tool for the Evaluation and Treatment of Sepsis in the ICU: A
      Randomized Controlled Trial.
AB  - OBJECTIVES: To determine whether addition of an electronic sepsis evaluation and
      management tool to electronic sepsis alerting improves compliance with treatment
      guidelines and clinical outcomes in septic ICU patients. DESIGN: A pragmatic
      randomized trial. SETTING: Medical and surgical ICUs of an academic, tertiary
      care medical center. PATIENTS: Four hundred and seven patients admitted during a
      4-month period to the medical or surgical ICU with a diagnosis of sepsis
      established at the time of admission or in response to an electronic sepsis
      alert. INTERVENTIONS: Patients were randomized to usual care or the availability
      of an electronic tool capable of importing, synthesizing, and displaying sepsis
      related data from the medical record, using logic rules to offer individualized
      evaluations of sepsis severity and response to therapy, informing users about
      evidence-based guidelines, and facilitating rapid order entry. MEASUREMENTS AND
      MAIN RESULTS: There was no difference between the electronic tool (218 patients)
      and usual care (189 patients) with regard to the primary outcome of time to
      completion of all indicated Surviving Sepsis Campaign 6-hour Sepsis Resuscitation
      Bundle elements (hazard ratio, 1.98; 95% CI, 0.75-5.20; p = 0.159) or time to
      completion of each element individually. ICU mortality, ICU-free days, and
      ventilator-free days did not differ between intervention and control. Providers
      used the tool to enter orders in only 28% of available cases. CONCLUSIONS: A
      comprehensive electronic sepsis evaluation and management tool is feasible and
      safe but did not influence guideline compliance or clinical outcomes, perhaps due
      to low utilization.

PMID- 25867907
TI  - Patient Mortality Is Associated With Staff Resources and Workload in the ICU: A
      Multicenter Observational Study.
AB  - OBJECTIVE: Matching healthcare staff resources to patient needs in the ICU is a
      key factor for quality of care. We aimed to assess the impact of the staffing-to
      patient ratio and workload on ICU mortality. DESIGN: We performed a multicenter
      longitudinal study using routinely collected hospital data. SETTING: Information
      pertaining to every patient in eight ICUs from four university hospitals from
      January to December 2013 was analyzed. PATIENTS: A total of 5,718 inpatient stays
      were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We used a
      shift-by-shift varying measure of the patient-to-caregiver ratio in combination
      with workload to establish their relationships with ICU mortality over time,
      excluding patients with decision to forego life-sustaining therapy. Using a
      multilevel Poisson regression, we quantified ICU mortality-relative risk,
      adjusted for patient turnover, severity, and staffing levels. The risk of death
      was increased by 3.5 (95% CI, 1.3-9.1) when the patient-to-nurse ratio was
      greater than 2.5, and it was increased by 2.0 (95% CI, 1.3-3.2) when the patient
      to-physician ratio exceeded 14. The highest ratios occurred more frequently
      during the weekend for nurse staffing and during the night for physicians (p <
      0.001). High patient turnover (adjusted relative risk, 5.6 [2.0-15.0]) and the
      volume of life-sustaining procedures performed by staff (adjusted relative risk,
      5.9 [4.3-7.9]) were also associated with increased mortality. CONCLUSIONS: This
      study proposes evidence-based thresholds for patient-to-caregiver ratios, above
      which patient safety may be endangered in the ICU. Real-time monitoring of
      staffing levels and workload is feasible for adjusting caregivers' resources to
      patients' needs.

PMID- 25867909
TI  - Regio- and stereoselective iodoacyloxylations of alkynes.
AB  - A new method for the regioselective and stereoselective iodoacyloxylation of
      alkynes has been developed. This protocol utilizes a combination of an
      iodobenzene dicarboxylate and iodine to functionalize a series of activated and
      unactivated alkynes in an entirely selective and predictable fashion. The
      resultant iodo-enol esters were subsequently coupled with boronic acids to afford
      tetrasubstituted alkene derivatives, which could be further converted to the
      corresponding 1,1-disubstituted acetophenone. 

PMID- 25867908
TI  - Monocyte Tumor Necrosis Factor-alpha-Converting Enzyme Catalytic Activity and
      Substrate Shedding in Sepsis and Noninfectious Systemic Inflammation.
AB  - OBJECTIVES: To determine the effect of severe sepsis on monocyte tumor necrosis
      factor-alpha-converting enzyme baseline and inducible activity profiles. DESIGN:
      Observational clinical study. SETTING: Mixed surgical/medical teaching hospital
      ICU. PATIENTS: Sixteen patients with severe sepsis, 15 healthy volunteers, and
      eight critically ill patients with noninfectious systemic inflammatory response
      syndrome. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Monocyte expression
      of human leukocyte antigen-D-related peptide, sol-tumor necrosis factor
      production, tumor necrosis factor-alpha-converting enzyme expression and
      catalytic activity, tumor necrosis factor receptor 1 and 2 expression, and
      shedding at 48-hour intervals from day 0 to day 4, as well as p38-mitogen
      activated protein kinase expression. Compared with healthy volunteers, both
      sepsis and systemic inflammatory response syndrome patients' monocytes expressed
      reduced levels of human leukocyte antigen-D-related peptide and released less sol
      tumor necrosis factor on in vitro lipopolysaccharide stimulation, consistent with
      the term monocyte deactivation. However, patients with sepsis had substantially
      elevated levels of basal tumor necrosis factor-alpha-converting enzyme activity
      that were refractory to lipopolysaccharide stimulation and this was accompanied
      by similar changes in p38-mitogen activated protein kinase signaling. In patients
      with systemic inflammatory response syndrome, monocyte basal tumor necrosis
      factor-alpha-converting enzyme, and its induction by lipopolysaccharide, appeared
      similar to healthy controls. Changes in basal tumor necrosis factor-alpha
      converting enzyme activity at day 0 for sepsis patients correlated with Acute
      Physiology and Chronic Health Evaluation II score and the attenuated tumor
      necrosis factor-alpha-converting enzyme response to lipopolysaccharide was
      associated with increased mortality. Similar changes in monocyte tumor necrosis
      factor-alpha-converting enzyme activity could be induced in healthy volunteer
      monocytes using an in vitro two-hit inflammation model. Patients with sepsis also
      displayed reduced shedding of monocyte tumor necrosis factor receptors upon
      stimulation with lipopolysaccharide. CONCLUSIONS: Monocyte tumor necrosis factor
      alpha-converting enzyme catalytic activity appeared altered by sepsis and may
      result in reduced shedding of tumor necrosis factor receptors. Changes seemed
      specific to sepsis and correlated with illness severity. A better understanding
      of how tumor necrosis factor-alpha-converting enzyme function is altered during
      sepsis will enhance our understanding of sepsis pathophysiology, which will help
      in the assessment of patient inflammatory status and ultimately may provide new
      strategies to treat sepsis.

PMID- 25867910
TI  - Surveillance for seasonal influenza virus prevalence in hospitalized children
      with lower respiratory tract infection in Guangzhou, China during the post
      pandemic era.
AB  - BACKGROUND: Influenza A(H1N1)pdm09, A(H3N2) and B viruses have co-circulated in
      the human population since the swine-origin human H1N1 pandemic in 2009. While
      infections of these subtypes generally cause mild illnesses, lower respiratory
      tract infection (LRTI) occurs in a portion of children and required
      hospitalization. The aim of our study was to estimate the prevalence of these
      three subtypes and compare the clinical manifestations in hospitalized children
      with LRTI in Guangzhou, China during the post-pandemic period. METHODS: Children
      hospitalized with LRTI from January 2010 to December 2012 were tested for
      influenza A/B virus infection from their throat swab specimens using real-time
      PCR and the clinical features of the positive cases were analyzed. RESULTS: Of
      3637 hospitalized children, 216 (5.9%) were identified as influenza A or B
      positive. Infection of influenza virus peaked around March in Guangzhou each year
      from 2010 to 2012, and there were distinct epidemics of each subtype. Influenza
      A(H3N2) infection was more frequently detected than A(H1N1)pdm09 and B, overall.
      The mean age of children with influenza A virus (H1N1/H3N2) infection was younger
      than those with influenza B (34.4 months/32.5 months versus 45 months old;
      p<0.005). Co-infections of influenza A/ B with mycoplasma pneumoniae were found
      in 44/216 (20.3%) children. CONCLUSIONS: This study contributes the understanding
      to the prevalence of seasonal influenza viruses in hospitalized children with
      LRTI in Guangzhou, China during the post pandemic period. High rate of mycoplasma
      pneumoniae co-infection with influenza viruses might contribute to severe disease
      in the hospitalized children.

PMID- 25867912
TI  - Comparison of once a day rifaximin to twice a day dosage in the prevention of
      recurrence of hepatic encephalopathy in patients with chronic liver disease.
AB  - BACKGROUND: Rifaximin has been used for prevention of recurrence of hepatic
      encephalopathy in twice a day dosage. The drug is expensive and lower dising may
      be possible. OBJECTIVE: To determine the efficacy of rifaximin once a day dose in
      the prevention of hepatic encephalopathy (HE) in patients with liver cirrhosis as
      compared with twice daily dose of rifaximin. METHODS: This Randomized control
      trial was carried out at the Department of Gastroenterology and Hepatology, Shifa
      International Hospital, Islamabad, Pakistan from November 2012 to February 2014.
      Patients with known chronic liver disease with at least one episode of HE in the
      past were randomized to group A (rifaximin 550 mg OD) and group B (rifaximin 550
      mg BD), after fulfilling the inclusion criteria. Each patient was followed for 6
      months for any episode of HE. Patients in each group were identified for any
      breakthrough episode of encephalopathy during this period. Data were analyzed
      using SPSS version 16. Chi-squared test and t-test were applied where required to
      determine the significant difference between the two groups. RESULTS: There were
      a total of 306 patients: 128 patients in Group A while 178 in group B. Majority
      of patients (75.81%) had hepatitis C virus with mean age of 52.30 +/- 9.92, MELD
      score 13.58 +/- 8.3, and 55.22% were in Child-Pugh B. Eighty-one patients had an
      episode of HE during the study period. There were 27 patients in group A and 54
      patients in group B with breakthrough episode of HE (P = 0.088). CONCLUSION: This
      study suggests that there is no significant difference in rifaximin once a day or
      twice daily dose in preventing HE.

PMID- 25867911
TI  - High glucose, glucose fluctuation and carbonyl stress enhance brain microvascular
      endothelial barrier dysfunction: Implications for diabetic cerebral
      microvasculature.
AB  - We previously demonstrated that in normal glucose (5mM), methylglyoxal (MG, a
      model of carbonyl stress) induced brain microvascular endothelial cell (IHEC)
      dysfunction that was associated with occludin glycation and prevented by N
      acetylcysteine (NAC). Herein, we investigated the impact of high glucose and low
      GSH, conditions that mimicked the diabetic state, on MG-induced IHEC dysfunction.
      MG-induced loss of transendothelial electrical resistance (TEER) was potentiated
      in IHECs cultured for 7 or 12 days in 25 mM glucose (hyperglycemia); moreover,
      barrier function remained disrupted 6h after cell transfer to normal glucose
      media (acute glycemic fluctuation). Notably, basal occludin glycation was
      elevated under these glycemic states. TEER loss was exaggerated by inhibition of
      glutathione (GSH) synthesis and abrogated by NAC, which corresponded to GSH
      decreases and increases, respectively. Significantly, glyoxalase II activity was
      attenuated in hyperglycemic cells. Moreover, hyperglycemia and GSH inhibition
      increased MG accumulation, consistent with a compromised capacity for MG
      elimination. alpha-Oxoaldehydes (MG plus glyoxal) levels were elevated in
      streptozotocin-induced diabetic rat plasma. Immunohistochemistry revealed a
      prevalence of MG-positive, but fewer occludin-positive microvessels in the
      diabetic brain in vivo, and Western analysis confirmed an increase in MG-occludin
      adducts. These results provide the first evidence that hyperglycemia and acute
      glucose fluctuation promote MG-occludin formation and exacerbate brain
      microvascular endothelial dysfunction. Low occludin expression and high glycated
      occludin contents in diabetic brain in vivo are factors that would contribute to
      the dysfunction of the cerebral microvasculature during diabetes.

PMID- 25867914
TI  - Corrigendum: antioxidant effect of carnosine treatment on renal oxidative stress
      in streptozotocin-induced diabetic rats.

PMID- 25867915
TI  - Political Correctness of Medical Documentation.

PMID- 25867913
TI  - Tenofovir Alafenamide Versus Tenofovir Disoproxil Fumarate in the First Protease
      Inhibitor-Based Single-Tablet Regimen for Initial HIV-1 Therapy: A Randomized
      Phase 2 Study.
AB  - OBJECTIVES: To evaluate the safety and efficacy of the novel tenofovir prodrug,
      tenofovir alafenamide (TAF), as part of the first protease inhibitor-based single
      tablet regimen (STR) for initial treatment of HIV-1 infection. METHODS:
      Antiretroviral therapy (ART)-naive adults with estimated glomerular filtration
      rate >= 70 mL/min were randomized 2:1 to receive the
      darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) STR (TAF: N
      = 103) or darunavir + cobicistat + emtricitabine/tenofovir disoproxil fumarate
      (TDF: N = 50) once daily with matched placebos for 48 weeks. RESULTS: At week 24,
      viral suppression (HIV-1 RNA <50 copies/mL) rates were similar (TAF 74.8% vs. TDF
      74.0%). At week 48, rates were TAF 76.7% vs. TDF 84.0%; the difference was driven
      by higher rate of discontinuations in TAF (6.8%) vs. TDF (2%). Among those with
      virologic failure, none developed resistance. Most adverse events were of
      mild/moderate severity. The mean change in serum creatinine from baseline at week
      48 was 0.06 mg/dL (95% confidence interval: 0.04 to 0.08) for TAF vs. 0.09 mg/dL
      (95% confidence interval: 0.05 to 0.14) for TDF (P = 0.053). The % change in
      retinol binding protein/Cr ratio was +9 (TAF) vs. +54 (TDF), P = 0.003; the %
      change in urine beta-2 microglobulin/Cr ratio was -42.0 (TAF) vs. +2.3 (TDF), P =
      0.002. The % change in hip bone mineral density (BMD) was -0.84 (TAF) vs. -3.82
      (TDF), P < 0.001 and in spine BMD was -1.57 (TAF) vs. -3.62 (TDF), P = 0.003.
      There were no fractures in either group. CONCLUSIONS: The TAF arm had
      significantly improved renal and bone safety parameters: less proteinuria and
      less change in hip and spine BMD, consistent with results from a similarly
      designed study of the elvitegravir/C/F/TAF STR. This D/C/F/TAF STR offers a
      promising option for initial HIV treatment, with the high barrier to resistance
      of darunavir, and the potential for improved long-term renal and bone safety with
      TAF.

PMID- 25867916
TI  - Non-invasive assessment of the efficacy of new therapeutics for intestinal
      pathologies using serial endoscopic imaging of live mice.
AB  - Animal models of inflammatory bowel disease (IBD) and colorectal cancer (CRC)
      have provided significant insight into the cell intrinsic and extrinsic
      mechanisms that contribute to the onset and progression of intestinal diseases.
      The identification of new molecules that promote these pathologies has led to a
      flurry of activity focused on the development of potential new therapies to
      inhibit their function. As a result, various pre-clinical mouse models with an
      intact immune system and stromal microenvironment are now heavily used. Here we
      describe three experimental protocols to test the efficacy of new therapeutics in
      pre-clinical models of (1) acute mucosal damage, (2) chronic colitis and/or
      colitis-associated colon cancer, and (3) sporadic colorectal cancer. We also
      outline procedures for serial endoscopic examination that can be used to document
      the therapeutic response of an individual tumor and to monitor the health of
      individual mice. These protocols provide complementary experimental platforms to
      test the effectiveness of therapeutic compounds shown to be well tolerated by
      mice. 

PMID- 25867917
TI  - Assessment of toxicity of Moringa oleifera flower extract to Biomphalaria
      glabrata, Schistosoma mansoni and Artemia salina.
AB  - This study reports the effect of an aqueous extract from Moringa oleifera Lam.
      flowers on Biomphalaria glabrata embryos and adults and on Schistosoma mansoni
      adult worms. The extract contains tannins, saponins, flavones, flavonols,
      xanthones, and trypsin inhibitor activity. The toxicity of the extract on Artemia
      salina larvae was also investigated to determine the safety of its use for
      schistosomiasis control. After incubation for 24h, the flower extract
      significantly (p<0.05) delayed the development of B. glabrata embryos and
      promoted mortality of adult snails (LC50: 2.37+/-0.5mgmL(-1)). Furthermore,
      treatment with the extract disrupted the development of embryos generated by
      snails, with most of them remaining in the blastula stage while control embryos
      were already in the gastrula stage. Flower extract killed A. salina larvae with a
      LC50 value (0.2+/-0.015mgmL(-1)) lower than that determined for snails. A small
      reduction (17%) in molluscicidal activity was detected when flower extract
      (2.37mgmL(-1)) was exposed to tropical environmental conditions (UVI index
      ranging from 1 to 14, temperature from 25 to 30 degrees C, and 65% relative
      humidity). Toxicity to A. salina was also reduced (LC50 value of 0.28+/-0.01mgmL(
      1)). In conclusion, M. oleifera flower extract had deleterious effects on B.
      glabrata adults and embryos. However, unrestricted use to control schistosomiasis
      should be avoided due to the toxicity of this extract on A. salina. 

PMID- 25867918
TI  - Atypical trait inferences from facial cues in alexithymia.
AB  - It is often difficult to distinguish strangers' permanent facial shapes from
      their transient facial expressions, for example, whether they are scowling or
      have narrow-set eyes. Overinterpretation of ambiguous cues may contribute to the
      rapid character judgments we make about others. Someone with narrow eyes might be
      judged untrustworthy, because of strong associations between facial anger and
      threat. To test this hypothesis, we investigated the trait judgments made by
      individuals with severe alexithymia, associated with impaired recognition of
      facial emotion. Consistent with the hypothesis, alexithymic participants
      demonstrated reduced interrater consistency when judging the character traits of
      unfamiliar faces, and the presence of subtle emotions. Nevertheless, where
      alexithymics perceived, or misperceived, emotion cues, the character traits
      inferred thereafter were broadly typical. The finding that individuals with
      developmental deficits of emotion recognition exhibit atypical attribution of
      character traits, confirms the hypothesis that emotion-recognition mechanisms
      play a causal role in character judgments.

PMID- 25867919
TI  - Social anxiety and narrowed attentional breadth toward faces.
AB  - The amount of information that can be perceived and processed will be partly
      determined by attentional breadth (i.e., the scope of attention), which might be
      narrowed in social anxiety due to a negative attentional bias. The current study
      examined the effects of stimulus valence on socially anxious individuals'
      attentional breadth. Seventy-three undergraduate students completed a
      computerized dual-task experiment during which they were simultaneously presented
      with a facial picture at the center of the screen and a black circle (i.e., a
      target) at the periphery. Participants' task was to indicate the gender of the
      model in the picture and the location of the peripheral target. The peripheral
      target was presented either close to or far from the central picture. Higher
      levels of social anxiety were significantly associated with greater difficulties
      detecting the target presented far from the central facial pictures, suggesting
      that social anxiety is associated with narrowed attentional breadth around social
      cues. Narrowing of attentional breadth among socially anxious individuals might
      hamper their ability to process all available social cues, thereby perpetuating
      social anxiety.

PMID- 25867920
TI  - Rethinking the area of protection "natural resources" in life cycle assessment.
AB  - Life cycle impact assessment (LCIA) in classical life cycle assessment (LCA) aims
      at analyzing potential impacts of products and services typically on three so
      called areas of protection (AoPs): Natural Environment, Human Health, and Natural
      Resources. This paper proposes an elaboration of the AoP Natural Resources. It
      starts with analyzing different perspectives on Natural Resources as they are
      somehow sandwiched in between the Natural Environment (their cradle) and the
      human-industrial environment (their application). Reflecting different
      viewpoints, five perspectives are developed with the suggestion to select three
      in function of classical LCA. They result in three safeguard subjects: the Asset
      of Natural Resources, their Provisioning Capacity, and their role in Global
      Functions. Whereas the Provisioning Capacity is fully in function of humans, the
      global functions go beyond provisioning as they include nonprovisioning functions
      for humans and regulating and maintenance services for the globe as a whole,
      following the ecosystem services framework. A fourth and fifth safeguard subject
      has been identified: recognizing the role Natural Resources for human welfare,
      either specifically as building block in supply chains of products and services
      as such, either with or without their functions beyond provisioning. But as these
      are far broader as they in principle should include characterization of
      mechanisms within the human industrial society, they are considered as subjects
      for an integrated sustainability assessment (LCSA: life cycle sustainability
      assessment), that is, incorporating social, economic and environmental issues. 

PMID- 25867921
TI  - Lower Blood Pressure and Gray Matter Integrity Loss in Older Persons.
AB  - In contrast to middle age, it is unclear whether blood pressure (BP) in older
      persons is associated with cerebral small vessel disease (cSVD). The authors
      evaluated the association of BP with signs of cSVD as well as gray and white
      matter integrity in older persons. In 220 participants aged 75 years and older
      from the Discontinuation of Antihypertensive Treatment in the Elderly (DANTE)
      study, cSVD was assessed with conventional magnetic resonance imaging, and
      microstructural integrity with diffusion tensor and magnetization transfer (MT)
      imaging. BP measures were not associated with cSVD. However, lower systolic and
      diastolic BP and mean arterial pressure were associated with decreased gray
      matter MT ratio peak height and MT ratio in cortical gray matter. Mean arterial
      pressure was also associated with increased gray matter diffusivity. A lower
      level of BP was especially associated with worse gray matter integrity. Results
      suggest that not only upper but preferably lower thresholds of BP values should
      be observed in older persons.

PMID- 25867922
TI  - High-throughput spatial mapping of single-cell RNA-seq data to tissue of origin.
AB  - Understanding cell type identity in a multicellular organism requires the
      integration of gene expression profiles from individual cells with their spatial
      location in a particular tissue. Current technologies allow whole-transcriptome
      sequencing of spatially identified cells but lack the throughput needed to
      characterize complex tissues. Here we present a high-throughput method to
      identify the spatial origin of cells assayed by single-cell RNA-sequencing within
      a tissue of interest. Our approach is based on comparing complete, specificity
      weighted mRNA profiles of a cell with positional gene expression profiles derived
      from a gene expression atlas. We show that this method allocates cells to precise
      locations in the brain of the marine annelid Platynereis dumerilii with a success
      rate of 81%. Our method is applicable to any system that has a reference gene
      expression database of sufficiently high resolution. 

PMID- 25867924
TI  - Torands Revisited: Metal Sequestration and Self-Assembly of Cyclo-2,9-tris-1,10
      phenanthroline Hexaaza Macrocycles.
AB  - A series of novel toroidal cyclo-2,9-tris-1,10-phenanthroline macrocycles with an
      unusual hexaaza cavity are reported. Nickel-mediated Yamamoto aryl-aryl coupling
      was found to be a versatile tool for the cyclotrimerization of functionalized
      1,10-phenathroline precursors. Due to the now improved processability, both
      liquid-crystalline behavior in the bulk phase and two-dimensional self-assembly
      at the molecular level could be studied, for the first time, for a torand system.
      The macrocycles exhibited a strong affinity for the complexation of different
      metal cations, as evidenced by MALDI-TOF analysis and spectroscopic methods.
      Experimental results were correlated to an extensive computational study of the
      cyclo-2,9-tris-1,10-phenanthroline cavity and its binding mode for metal cations.
      Due to the combination of several interesting features, toroidal macrocycles may
      find future applications in the field of ion and charge transport through
      molecular channels, as well as for chemical sensing and molecular writing in
      surface-confined monolayers under STM conditions. 

PMID- 25867923
TI  - Spatial reconstruction of single-cell gene expression data.
AB  - Spatial localization is a key determinant of cellular fate and behavior, but
      methods for spatially resolved, transcriptome-wide gene expression profiling
      across complex tissues are lacking. RNA staining methods assay only a small
      number of transcripts, whereas single-cell RNA-seq, which measures global gene
      expression, separates cells from their native spatial context. Here we present
      Seurat, a computational strategy to infer cellular localization by integrating
      single-cell RNA-seq data with in situ RNA patterns. We applied Seurat to
      spatially map 851 single cells from dissociated zebrafish (Danio rerio) embryos
      and generated a transcriptome-wide map of spatial patterning. We confirmed
      Seurat's accuracy using several experimental approaches, then used the strategy
      to identify a set of archetypal expression patterns and spatial markers. Seurat
      correctly localizes rare subpopulations, accurately mapping both spatially
      restricted and scattered groups. Seurat will be applicable to mapping cellular
      localization within complex patterned tissues in diverse systems. 

PMID- 25867925
TI  - Serum Visfatin, Fetuin-A, and Pentraxin 3 Levels in Patients With Psoriasis and
      Their Relation to Disease Severity.
AB  - BACKGROUND: Psoriasis is a chronic immune-mediated inflammatory skin disease
      associated with increase of some pro-inflammatory mediators. We wanted to
      investigate whether there is a relationship between psoriasis and visfatin,
      fetuin-A and pentraxin 3 (PTX3)-pro-inflammatory mediators implicated in the
      development of insulin resistance (IR), metabolic syndrome, and atherosclerosis.
      METHODS: Visfatin, fetuin-A, and PTX3 concentrations were measured in 45 patients
      with plaque-type psoriasis and 45 healthy controls using enzyme-linked
      immunosorbent assay (ELISA). RESULTS: Serum levels of visfatin, fetuin-A, and
      PTX3 in patients with psoriasis were found to be higher than in healthy controls
      (P = 0.002, P = 0.009, P < 0.001, respectively). Psoriasis area and severity
      index (PASI) score correlated significantly with visfatin and fetuin-A levels (P
      = 0.011, P = 0.040, respectively). There was a significant positive correlation
      between visfatin and fetuin-A (P < 0.001). PTX3 levels were correlated positively
      with homeostasis model assessment (HOMA-IR), insulin, triglyceride (TG), and very
      low density lipoprotein cholesterol (VLDL; P = 0.009, P = 0.007, P = 0.023, P =
      0.024, respectively). CONCLUSIONS: Increased serum visfatin, fetuin-A, and PTX3
      levels, and the presence of positive correlation between visfatin, fetuin-A, and
      PASI score, probably reflect the inflammatory state and IR seen in psoriasis.

PMID- 25867926
TI  - Improving polyglucan production in cyanobacteria and microalgae via cultivation
      design and metabolic engineering.
AB  - Photosynthetic microorganisms, such as cyanobacteria and microalgae, are
      currently being investigated as alternative biomass resources for bioethanol
      production, owing to their benefits, including high-photosynthetic activity and
      whole-year cultivation without utilization of arable land. Polyglucans comprise
      the major carbohydrate content of these organisms. Polyglucans can be utilized as
      a carbon source for microbial fermentation. Although polyglucan production has so
      far been promoted by nutrient limitation, it must be further enhanced to
      accommodate market demand. This review focuses on the recent progress in the
      production of alpha-polyglucans such asglycogen and starch in cyanobacteria and
      green microalgae via cultivation design, including modifying the nutrient supply
      and replacing the growth medium. The control and manipulation of polyglucan
      metabolism necessitates the elucidation of the polyglucan production mechanism.
      We reviewed gene expression and metabolite accumulation profiles of cyanobacteria
      and green microalgae during nutrient limitation-stimulated alpha-polyglucan
      accumulation. We also focus on the enhancement in cyanobacterial glycogen
      production via the genetic engineering of glycolysis, CO2 concentration
      mechanism, and photosynthetic light-harvesting protein based on the polyglucan
      accumulation mechanism. The combined strategies of cultivation design and genetic
      engineering should be considered for further enhancement of polyglucan
      productivity for bioethanol production. 

PMID- 25867927
TI  - Perceived barriers to utilise methadone maintenance therapy among male injection
      drug users in rural areas of southern Thailand.
AB  - INTRODUCTION AND AIMS: Methadone maintenance therapy (MMT) has been proven to be
      effective and cost-effective in treating dependence on opioids. However, concerns
      remain that geographical, financial and other hidden barriers may hinder access
      to MMT, especially in rural areas where health services are limited. The
      objective of this study was to determine factors associated with utilisation of
      MMT by injection drug users (IDUs) living in Songkhla province. DESIGN AND
      METHODS: A cross-sectional study among 159 IDUs in Songkhla province of southern
      Thailand was conducted. Participants were recruited using a snowball technique.
      Data were collected from July 2013 to January 2014 via face-to-face interviews.
      RESULTS: Around one-forth (24.5%) of participants had difficulties travelling to
      MMT clinics because of the long distance, long travelling time and lack of a
      private vehicle. Twenty-four percent faced difficulties with the clinic's opening
      hours and 28% faced difficulties paying for the cost of travel. IDUs who utilised
      the MMT perceived risks of injection drug use differently compared with those who
      did not. Younger or Muslim IDUs were less likely to attend MMT. IDUs who
      perceived that MMT was effective were more likely to utilise MMT. DISCUSSION AND
      CONCLUSIONS: Physical accessibility, affordability and acceptability play an
      essential role in MMT utilisation. Developing alternatives that reduce the
      travelling time, costs for IDUs and more convenient operation hours to suit their
      lifestyles may increase the utilisation of MMT. Intensive consultation before
      starting MMT is highly recommended.

PMID- 25867929
TI  - Personomics.

PMID- 25867928
TI  - EPA Method 1615. Measurement of enterovirus and norovirus occurrence in water by
      culture and RT-qPCR. I. Collection of virus samples.
AB  - EPA Method 1615 was developed with a goal of providing a standard method for
      measuring enteroviruses and noroviruses in environmental and drinking waters. The
      standardized sampling component of the method concentrates viruses that may be
      present in water by passage of a minimum specified volume of water through an
      electropositive cartridge filter. The minimum specified volumes for surface and
      finished/ground water are 300 L and 1,500 L, respectively. A major method
      limitation is the tendency for the filters to clog before meeting the sample
      volume requirement. Studies using two different, but equivalent, cartridge filter
      options showed that filter clogging was a problem with 10% of the samples with
      one of the filter types compared to 6% with the other filter type. Clogging tends
      to increase with turbidity, but cannot be predicted based on turbidity
      measurements only. From a cost standpoint one of the filter options is preferable
      over the other, but the water quality and experience with the water system to be
      sampled should be taken into consideration in making filter selections. 

PMID- 25867930
TI  - Glycogen Storage Disorder due to Glycogen Branching Enzyme (GBE) Deficiency: A
      Diagnostic Dilemma.
AB  - Glycogen branching enzyme deficiency/Andersen disease can manifest with a
      spectrum of clinical phenotypes, making the diagnosis difficult. An 11-year-old
      Pakistani boy presented with a history of progressive weakness and delayed
      milestones. Echocardiography showed features of dilated cardiomyopathy. He was
      suspected to have congenital myopathy and was evaluated further. Muscle biopsy
      showed subsarcolemmal accumulation of basophilic material, which stained
      positively with Periodic acid-Schiff reagent (diastase-resistant).
      Ultrastructural examination revealed accumulation of structurally abnormal forms
      of filamentous glycogen, confirming the diagnosis as Andersen disease. As
      histopathological and immunohistochemical evaluation of muscle biopsies is not
      always diagnostic, ultrastructural examination may serve as a valuable adjunct in
      difficult cases. 

PMID- 25867931
TI  - Persistence of dual free internal rotation in NH4(+)(H2O).Hen=0-3 ion-molecule
      complexes: expanding the case for quantum delocalization in He tagging.
AB  - To explore the extent of the molecular cation perturbation induced by
      complexation with He atoms required for the application of cryogenic ion
      vibrational predissociation (CIVP) spectroscopy, we compare the spectra of a bare
      NH4(+)(H2O) ion (obtained using infrared multiple photon dissociation (IRMPD))
      with the one-photon CIVP spectra of the NH4(+)(H2O).He1-3 clusters. Not only are
      the vibrational band origins minimally perturbed, but the rotational fine
      structures on the NH and OH asymmetric stretching vibrations, which arise from
      the free internal rotation of the -OH2 and -NH3 groups, also remain intact in the
      adducts. To establish the location and the quantum mechanical delocalization of
      the He atoms, we carried out diffusion Monte Carlo (DMC) calculations of the
      vibrational zero point wave function, which indicate that the barriers between
      the three equivalent minima for the He attachment are so small that the He atom
      wave function is delocalized over the entire -NH3 rotor, effectively restoring C3
      symmetry for the embedded -NH3 group. 

PMID- 25867932
TI  - Detection of polycyclic aromatic hydrocarbons (PAHs) in raw menhaden fish oil
      using fluorescence spectroscopy: Method development.
AB  - Raw menhaden fish oil was developed for biomonitoring polycyclic aromatic
      hydrocarbons (PAHs) using fluorescence spectroscopy. Menhaden (Genus Brevoortia)
      were collected in 2010 and/or 2011 from Delaware Bay, New Jersey, USA; James
      River, Virginia, USA; Vermillion Bay, Louisiana, USA (VBLA); and Barataria Bay,
      Louisiana, USA (BBLA). Barataria Bay, Louisiana received heavy oiling from the
      Deepwater Horizon oil spill. Method development included determining optimal
      wavelengths for PAH detection, fish oil matrix interferences, and influence of
      solvent concentration on extraction. Results showed that some fish oils contained
      high molecular weight PAH-like compounds in addition to other fluorescent
      compounds such as albumin and vitamin A and vitamin E. None of these naturally
      occurring compounds interfered with detection of high molecular weight PAHs.
      However, data suggested that the lipid component of fish oil was altering
      fluorescence spectra by supporting the formation of PAH excimers. For example,
      the most intense excitation wavelength for hydroxypyrene shifted from Ex285/Em430
      to Ex340/Em430. Comparison of Deepwater Horizon crude oil and fish oil spectra
      indicated that some fish oils contained crude oil-like PAHs. Using wavelengths of
      Ex360/Em430, fish oil concentrations were calculated as 3.92 MUg/g, 0.61 MUg/g,
      and 0.14 MUg/g for a Delaware Bay sample, BBLA 2011, and VBLA 2011, respectively.
      Overall, these results supported using menhaden fish oil to track PAH exposures
      spatially and temporally.

PMID- 25867934
TI  - What portion of the soft tissue artefact requires compensation when estimating
      joint kinematics?
AB  - When joint kinematics is analyzed using noninvasive stereophotogrammetry,
      movements of the skin markers relative to the underlying bone are regarded as
      artefacts (soft tissue artefact (STA)). Recent literature suggests that an
      appropriate estimation of joint kinematics may be obtained by compensating for
      only a portion of the STA, but no evidence for this case has been reported, and
      which portion of the STA should be selected remains an issue. The aim of this
      study was to fill this gap. A modal approach was used to represent the STA. This
      resulted in a series of additive components (modes) and in the possibility to
      select a subset of them. The following STA definitions were used: individual skin
      marker displacement (MD), marker-cluster geometrical transformation (GT), and
      skin envelope shape variation (SV). An STA approximation for each of the three
      definitions was obtained by ordering modes on the basis of their contribution to
      the total STA energy and truncating the relevant series at 90% of it. A fourth
      approximation was obtained when the GT definition was used, by selecting the
      modes that represented the marker-cluster rigid transformation (i.e., three
      translation and three rotation modes). The different STA approximations were
      compared using data obtained during the stance phase of running of three
      volunteers carrying both pin and skin markers. The STA was measured and knee
      joint kinematics estimated using four skin marker datasets compensated for the
      above-mentioned STA approximations. Accuracy was assessed by comparing results to
      the reference kinematics obtained using pin markers. The different approximations
      resulted in different numbers of modes. For joint angles, the compensation
      efficiency across the STA approximations based on an energy threshold was almost
      equivalent. The median root mean square errors (RMSEs) were below 1 deg for
      flexion/extension and 2 deg for both abduction/adduction and internal/external
      rotation. For the joint displacements, the compensation efficiency depended on
      the STA approximation. Median RMSEs for anterior/posterior displacement ranged
      from 1 to 4 mm using either MD, GT, or SV truncated series. The RMSEs were
      virtually null when the STA was approximated using only the GT rigid modes. This
      result, together with the limited number of modes used by this approximation
      (i.e., three translations and three rotations of the marker-cluster), makes the
      STA rigid component and a good candidate for designing an STA model to be
      incorporated in an enhanced bone pose estimator. 

PMID- 25867933
TI  - Cellular and molecular characterization of human cardiac stem cells reveals key
      features essential for their function and safety.
AB  - Cell therapy of heart diseases is emerging as one of the most promising known
      treatments in recent years. Transplantation of cardiac stem cells (CSCs) may be
      one of the best strategies to cure adult or pediatric heart diseases. As these
      patient-derived stem cells need to be isolated from small heart biopsies, it is
      important to select the best isolation method and CSC subpopulation with the best
      cardiogenic functionality. We employed three different protocols including c
      KIT(+) cell sorting, clonogenic expansion, and explants culture to isolate c
      KIT(+) cells, clonogenic expansion-derived cells (CEDCs), and cardiosphere
      derived cells (CDCs), respectively. Evaluation of isolated CSC characteristics in
      vitro and after rat myocardial infarction (MI) model transplantation revealed
      that although c-KIT(+) and CDCs had higher MI regenerative potential, CEDCs had
      more commitment into cardiomyocytes and needed lower passages that were essential
      to reach a definite cell count. Furthermore, genome-wide expression analysis
      showed that subsequent passages caused changes in characteristics of cells,
      downregulation of cell cycle-related genes, and upregulation of differentiation
      and carcinogenic genes, which might lead to senescence, commitment, and possible
      tumorigenicity of the cells. Because of different properties of CSC
      subpopulations, we suggest that appropriate CSCs subpopulation should be chosen
      based on their experimental or clinical use. 

PMID- 25867935
TI  - EFFECTS OF FLUID AND COMPUTED TOMOGRAPHIC TECHNICAL FACTORS ON CONSPICUITY OF
      CANINE AND FELINE NASAL TURBINATES.
AB  - Turbinate destruction is an important diagnostic criterion in canine and feline
      nasal computed tomography (CT). However decreased turbinate visibility may also
      be caused by technical CT settings and nasal fluid. The purpose of this
      experimental, crossover study was to determine whether fluid reduces conspicuity
      of canine and feline nasal turbinates in CT and if so, whether CT settings can
      maximize conspicuity. Three canine and three feline cadaver heads were used.
      Nasal slabs were CT-scanned before and after submerging them in a water bath;
      using sequential, helical, and ultrahigh resolution modes; with images in low,
      medium, and high frequency image reconstruction kernels; and with application of
      additional posterior fossa optimization and high contrast enhancing filters.
      Visible turbinate length was measured by a single observer using manual tracing.
      Nasal density heterogeneity was measured using the standard deviation (SD) of
      mean nasal density from a region of interest in each nasal cavity. Linear mixed
      effect models using the R package 'nlme', multivariable models and standard post
      hoc Tukey pair-wise comparisons were performed to investigate the effect of
      several variables (nasal content, scanning mode, image reconstruction kernel,
      application of post reconstruction filters) on measured visible total turbinate
      length and SD of mean nasal density. All canine and feline water-filled nasal
      slabs showed significantly decreased visibility of nasal turbinates (P < 0.001).
      High frequency kernels provided the best turbinate visibility and highest SD of
      aerated nasal slabs, whereas medium frequency kernels were optimal for water
      filled nasal slabs. Scanning mode and filter application had no effect on
      turbinate visibility. 

PMID- 25867936
TI  - Incision and drainage versus incision and drainage with primary closure and use
      of closed suction drain in acute abscesses.
AB  - INTRODUCTION: Acute abscesses are one of the most common acute problems seen in
      the surgical department of the R.D. Gardi Medical College (Ujjain, Madyha
      Pradesh, India). A conventional method used in the treatment of abscess is
      incision and drainage. The aim of this study was to compare the conventional
      method of incision and drainage with the alternative method of incision and
      drainage with primary closure, and use of a closed suction drain to reduce
      secondary infection. MATERIAL AND METHODS: One hundred fifty patients admitted to
      the authors' hospital with an abscess were randomly divided into 2 groups: Group
      A included 75 patients treated by incision and drainage with primary closure and
      use of a closed suction drain; Group B included 75 patients treated by the
      conventional method of incision and drainage only. RESULTS: Healing time in Group
      A patients was less than that of Group B patients. The length of hospital stay
      and number of additional hospital visits for dressing changes were less for Group
      A patients. CONCLUSION: The method of incision and drainage with primary closure
      combined with use of a closed suction drain is more effective than that of
      incision and drainage only.

PMID- 25867937
TI  - Dermatological manifestations among patients on maintenance hemodialysis.
AB  - Introduction. Patients with chronic kidney disease on hemodialysis (HD) undergo
      many dermatological signs and symptoms during treatment. The aim of this study
      was to investigate the prevalence of skin manifestations among the patients on
      maintenance HD in the HD center of Boo Ali-Sina Hospital (Qazvin, Iran) and
      compare them with the general population. METHODS: From June 2012 to July 2012 a
      case-controlled study was performed with 149 patients with end-stage renal
      disease undergoing regular HD (HD group) and 150 individuals who were randomly
      selected (control group) from healthy hospital staff at Boo Ali-Sina Hospital. A
      dermatologist examined all individuals in both groups to assess of skin, hair,
      nail, and mucosal tissues. RESULTS: Overall, 108 of the patients in the HD group
      and 54 of the individuals in the control group were found to have at least 1
      cutaneous and mocusal manifestation. Pruritus, skin discoloration, ecchymosis,
      drying and hair fragility, leukonychia, absent lunula, and half and half nails
      were more frequent in the HD group than compared to the control group (P < 0.05).
      Although no significant correlation between dermatological manifestations and age
      >= 65 or diabetes mellitus were made, multiple logistic regression analysis
      indicated that male sex, hypertension, and long-term HD were associated with
      dermatological manifestations. DISCUSSION: In the present study, cutaneous and
      mocusal manifestations ranged from 36% in the control group to 72.4% in the HD
      group. The results also indicate a relationship between cutaneous and mocusal
      manifestations, and male sex, hypertension, and duration of dialysis in HD
      patients.    .

PMID- 25867938
TI  - [Not Available].
AB  - OBJECTIVE: The purpose of this study was to reveal the effect of N-acetylcysteine
      (NAC) on random-skin flaps in rats. INTRODUCTION: N-acetylcysteine is an agent
      among free radical scavengers which is used primarily as a mucolitic agent.
      Experimental studies have demonstrated protective effects of NAC on hepatic,
      renal, lung, and intestinal injuries. METHODS: Wistar female rats were divided
      into 2 groups (control and NAC group), and the NAC group received intramuscular
      injections for 7 days. Flaps were raised on day 2 and rats were sacrified on day
      7. Skin samples from the second cm and fifth cm of the skin flap were collected
      for biochemical and histopathological examinations. RESULTS: The mean necrotic
      area ratios in the control and NAC group were 38% and 12%, respectively (P
      <0.001). Malondialdehyde (MDA) levels were significantly lower in skin samples
      collected from the control group as compared to samples obtained from the NAC
      group (P = 0.002). Superoxide dismustase (SOD) activity was significantly higher
      in the NAC group (P < 0.0001). Histopathologically, a significant increase in
      macrophage and fibroblast activity was observed in the NAC group. Mononuclear
      cell infiltration and fibroblast activity had increased, especially in samples
      from the fifth cm of the skin flap in the NAC group. The histopathological
      evaluation in the NAC group revealed protective effects of NAC. CONCLUSIONS:
      Treatment of rats with NAC significantly reduced flap necrosis and MDA levels
      while increasing SOD levels. These data suggest that NAC has a protective role in
      flap survival and demonstrates preventive effects against flap necrosis.  .

PMID- 25867939
TI  - The use of negative pressure wound therapy with an automated, volumetric fluid
      administration: an advancement in wound care.
AB  - Introduction. This small pilot study introduces initial clinical experience with
      a system combining negative pressure wound therapy and negative pressure wound
      therapy with instillation (NPWT/NPWTi, V.A.C. ULTATM Negative Pressure Wound
      Therapy, KCI USA, Inc, San Antonio, TX). MATERIALS AND METHODS: The NPWT system
      with instillation delivers controlled volumetric fluid instillation, and uses
      instillation- specific reticulated open-cell foam (ROCF) dressings: Dressing A
      (ROCF-V, V.A.C. VeraFloTM Dressing, KCI USA, Inc, San Antonio, TX) or Dressing B
      (ROCF-VC, V.A.C. VeraFlo CleanseTM Dressing, KCI USA, Inc, San Antonio, TX). Six
      patients ranging in age from 26-83 years were treated with either NPWT with
      instillation and Dressing A or Dressing B, and Microcyn(r) antiseptic solution
      (Oculus Innovative Sciences, Petaluma, CA) (n = 5) or quarter- strength Dakin's
      Solution(r) (Century Pharmaceuticals, Indianapolis, IN) (n = 1), as the
      instillate. Negative pressure wound therapy was applied in 1 patient to a single
      wound using Dressing C (ROCF; V.A.C.(r) GranuFoamTM Dressing, KCI USA, Inc, San
      Antonio, TX) in one half of the wound, and Dressing B in the other half. In this
      patient series, instillation was repeated every 2-4 hours with a 5-10 minute soak
      time followed by negative pressure at -100 mm Hg to -125 mm Hg. All wounds were
      closed by skin graft or primary, secondary, or delayed primary intention.
      RESULTS: For the wound treated with NPWT only, no difference in degree or quality
      of granulation tissue formation was observed by either dressing. CONCLUSION: The
      system worked well across multiple wound types in either NPWT mode or NPWT with
      instillation mode, and no complications were observed. Larger patient studies
      with controls are needed to validate the clinical observations in this patient
      series.    .

PMID- 25867940
TI  - First record of autochthonous canine ehrlichiosis caused by Ehrlichia canis in
      Romania.
AB  - This case study describes the first genetically confirmed and clinically
      manifested autochthonous Ehrlichia canis infection in a 9-year-old female mixed
      breed dog from Romania. Health screening of the dog included clinical
      examination, evaluation of stained peripheral blood smear and hematologic
      variables, as well as serologic testing and molecular analysis. Clinical signs
      included fever, apathy, dehydration, pale mucous membranes, and weakness. The
      microscopic examination of the blood smear and immunologic assays for Borrelia
      burgdorferi, Anaplasma phagocytophilum, and E canis antibodies, and for
      Dirofilaria immitis antigen yielded negative results. Hematologic abnormalities
      included moderate nonregenerative anemia, leucopenia with neutropenia, and
      moderate thrombocytopenia. The biochemical abnormalities identified were
      hypoalbuminemia, and mildly increased serum enzyme activities of AST and ALT. In
      addition, increased urea and creatinine levels associated with low urine specific
      gravity and proteinuria were also present. Nested PCR amplification of the
      partial E canis 16S rRNA gene demonstrated the presence of this rickettsial
      pathogen in the dog's blood, which subsequently was confirmed through sequencing
      based on the 100% homology with GenBank deposited E canis isolates. After
      specific treatment with doxycycline (10 mg/kg, orally, SID) for one month, the
      proteinuria, and hematologic and serum biochemical abnormalities with the
      exception of mild azotemia resolved. This report supports the geographical
      expansion of canine ehrlichiosis caused by E canis in nonendemic regions of
      Europe. 

PMID- 25867941
TI  - Generation of photovoltage in graphene on a femtosecond timescale through
      efficient carrier heating.
AB  - Graphene is a promising material for ultrafast and broadband photodetection.
      Earlier studies have addressed the general operation of graphene-based
      photothermoelectric devices and the switching speed, which is limited by the
      charge carrier cooling time, on the order of picoseconds. However, the generation
      of the photovoltage could occur at a much faster timescale, as it is associated
      with the carrier heating time. Here, we measure the photovoltage generation time
      and find it to be faster than 50 fs. As a proof-of-principle application of this
      ultrafast photodetector, we use graphene to directly measure, electrically, the
      pulse duration of a sub-50 fs laser pulse. The observation that carrier heating
      is ultrafast suggests that energy from absorbed photons can be efficiently
      transferred to carrier heat. To study this, we examine the spectral response and
      find a constant spectral responsivity of between 500 and 1,500 nm. This is
      consistent with efficient electron heating. These results are promising for
      ultrafast femtosecond and broadband photodetector applications. 

PMID- 25867942
TI  - Nanoscale form dictates mesoscale function in plasmonic DNA-nanoparticle
      superlattices.
AB  - The nanoscale manipulation of matter allows properties to be created in a
      material that would be difficult or even impossible to achieve in the bulk state.
      Progress towards such functional nanoscale architectures requires the development
      of methods to precisely locate nanoscale objects in three dimensions and for the
      formation of rigorous structure-function relationships across multiple size
      regimes (beginning from the nanoscale). Here, we use DNA as a programmable ligand
      to show that two- and three-dimensional mesoscale superlattice crystals with
      precisely engineered optical properties can be assembled from the bottom up. The
      superlattices can transition from exhibiting the properties of the constituent
      plasmonic nanoparticles to adopting the photonic properties defined by the
      mesoscale crystal (here a rhombic dodecahedron) by controlling the spacing
      between the gold nanoparticle building blocks. Furthermore, we develop a
      generally applicable theoretical framework that illustrates how crystal habit can
      be a design consideration for controlling far-field extinction and light
      confinement in plasmonic metamaterial superlattices. 

PMID- 25867943
TI  - Fast and accurate construction of ultra-dense consensus genetic maps using
      evolution strategy optimization.
AB  - Our aim was to develop a fast and accurate algorithm for constructing consensus
      genetic maps for chip-based SNP genotyping data with a high proportion of shared
      markers between mapping populations. Chip-based genotyping of SNP markers allows
      producing high-density genetic maps with a relatively standardized set of marker
      loci for different mapping populations. The availability of a standard high
      throughput mapping platform simplifies consensus analysis by ignoring unique
      markers at the stage of consensus mapping thereby reducing mathematical
      complicity of the problem and in turn analyzing bigger size mapping data using
      global optimization criteria instead of local ones. Our three-phase analytical
      scheme includes automatic selection of ~100-300 of the most informative
      (resolvable by recombination) markers per linkage group, building a stable
      skeletal marker order for each data set and its verification using jackknife re
      sampling, and consensus mapping analysis based on global optimization criterion.
      A novel Evolution Strategy optimization algorithm with a global optimization
      criterion presented in this paper is able to generate high quality, ultra-dense
      consensus maps, with many thousands of markers per genome. This algorithm
      utilizes "potentially good orders" in the initial solution and in the new
      mutation procedures that generate trial solutions, enabling to obtain a consensus
      order in reasonable time. The developed algorithm, tested on a wide range of
      simulated data and real world data (Arabidopsis), outperformed two tested state
      of-the-art algorithms by mapping accuracy and computation time. 

PMID- 25867944
TI  - Diastereoselective synthesis of P-chirogenic phosphoramidate prodrugs of
      nucleoside analogues (ProTides) via copper catalysed reaction.
AB  - The first copper-catalysed diastereoselective synthesis of P-chiral
      phosphoramidate prodrugs (ProTides) is reported. This procedure allows the
      synthesis of diastereomeric-enriched mixtures of ProTides. Application of this
      methodology to the asymmetric phosphorylation of purine and pyrimidine nucleoside
      analogues is presented. 

PMID- 25867945
TI  - Catalytic enantioselective intramolecular aza-diels-alder reactions.
AB  - A readily available chiral Bronsted acid was identified as an efficient catalyst
      for intramolecular Povarov reactions. Polycyclic amines containing three
      contiguous stereogenic centers were obtained with excellent stereocontrol in a
      single step from secondary anilines and aldehydes possessing a pendent
      dienophile. These transformations constitute the first examples of catalytic
      enantioselective intramolecular aza-Diels-Alder reactions. 

PMID- 25867946
TI  - Diagnostic values of the QuantiFERON-TB Gold In-tube assay carried out in China
      for diagnosing pulmonary tuberculosis.
AB  - BACKGROUND: Interferon-release assays (IGRAs) for diagnosing active pulmonary
      tuberculosis (PTB) are not yet fully validated, particularly in high TB-endemic
      areas as the People's Republic of China (PRC). The aim of this report was to
      assess the performance of the QuantiFERON-TB Gold In-tube (QFT-GIT) and
      tuberculin skin test (TST), in addition to microbiological results, as
      contributors for diagnosing active PTB in the PRC. METHODS/PRINCIPAL FINDINGS: A
      total of 300 PTB patients, 41 disease controls (DC) and 59 healthy community
      controls (HCC) were included prospectively between May 2010 and April 2011 from
      two provinces of the PRC (Heilongjiang and Zhejiang). The QFT-GIT and TST yielded
      an overall sensitivity for active TB of 80.9% and 86.2%, and a specificity of
      36.6% and 26.8%, respectively. The province of origin and smear microscopy status
      did not significantly impact the diagnostic values for PTB. However, using the
      TST with a 10 mm cut-off point, a significantly higher proportion of LTBI was
      observed in the DC than the HCC (p=0.01). Discordant results between the QFT-GIT
      and TST were found among 1/3 of the PTB, HCC and DC. Two-thirds of the
      individuals presented TST-positive/QFT-GIT-negative discordant results. The TST
      negative/QFT-GIT-positive result was not associated with age or bacillary load.
      Cumulative QFT-GIT and TST positive results increased the overall sensitivity
      (95.9%), but it was associated with a dramatic decrease of the overall
      specificity (24.8%) leading to a suboptimal PPV (80.1%) and a low NPV (61.1%).
      CONCLUSIONS/SIGNIFICANCE: The usefulness of the QFT-GIT to diagnose active TB in
      high TB-endemic countries remains doubtful because like the TST, the QFT-GIT
      cannot distinguish between LTBI and active TB. Used as single stand-alone tests,
      both the QFT-GIT and TST have very limited roles in the diagnosis of active PTB.
      However, the combined use of SM, the TST and QFT-GIT may allow for the exclusion
      of ATB.

PMID- 25867947
TI  - Busulfan as a myelosuppressive agent for generating stable high-level bone marrow
      chimerism in mice.
AB  - Bone marrow transplantation (BMT) is often used to replace the bone marrow (BM)
      compartment of recipient mice with BM cells expressing a distinct biomarker
      isolated from donor mice. This technique allows for identification of donor
      derived hematopoietic cells within the recipient mice, and can be used to isolate
      and characterize donor cells using various biochemical techniques. BMT typically
      relies on myeloablative conditioning with total body irradiation to generate
      niche space within the BM compartment of recipient mice for donor cell
      engraftment. The protocol we describe here uses myelosuppressive conditioning
      with the chemotherapeutic agent busulfan. Unlike irradiation, which requires the
      use of specialized facilities, busulfan conditioning is performed using
      intraperitoneal injections of 20 mg/kg busulfan until a total dose of 60-100
      mg/kg has been administered. Moreover, myeloablative irradiation can have toxic
      side effects and requires successful engraftment of donor cells for survival of
      recipient mice. In contrast, busulfan conditioning using these doses is generally
      well tolerated and mice survive without donor cell support. Donor BM cells are
      isolated from the femurs and tibiae of mice ubiquitously expressing green
      fluorescent protein (GFP), and injected into the lateral tail vein of conditioned
      recipient mice. BM chimerism is estimated by quantifying the number of GFP+ cells
      within the peripheral blood following BMT. Levels of chimerism >80% are typically
      observed in the peripheral blood 3-4 weeks post-transplant and remain established
      for at least 1 year. As with irradiation, conditioning with busulfan and BMT
      allows for the accumulation of donor BM-derived cells within the central nervous
      system (CNS), particularly in mouse models of neurodegeneration. This busulfan
      mediated CNS accumulation may be more physiological than total body irradiation,
      as the busulfan treatment is less toxic and CNS inflammation appears to be less
      extensive. We hypothesize that these cells can be genetically engineered to
      deliver therapeutics to the CNS. 

PMID- 25867948
TI  - Orbital Cellulitis and Subperiosteal Abscess: A 5-year Outcomes Analysis.
AB  - PURPOSE: Orbital cellulitis and subperiosteal abscess (SPA) are historically
      associated with poor outcomes. We seek to characterize current associations with
      abscess formation, surgical failure and vision loss. METHODS: All cases of
      orbital cellulitis presenting to an affiliated hospital between April 2008 and
      2013 were critically reviewed. RESULTS: Thirty patients met inclusion criteria.
      Average age was 28.7 +/- 24.4. The male to female ratio was 2:1. Abscesses were
      identified in 56.7% of patients. Adults were less likely than children to present
      with abscesses (28.6% vs. 81.3%, p = 0.008). Of the other factors analyzed, only
      antibiotic use before admission (70.5% vs. 23.1%, p = 0.03) and maximum
      restriction (-2.5 +/- 1.2 vs. -0.9 +/- 0.7, p = 0.008) were associated with SPA.
      Temperature at presentation (37.9 +/- 0.9 vs. 37.1 +/- 0.4, p = 0.04), relative
      proptosis (5.8 +/- 3.3 mm vs. 2.1 +/- 1.1, p = 0.002) and abscess volume (4.3 +/-
      1.3 mm(3) vs. 0.7 +/- 0.5 mm(3), p = 0.0004) were associated with progression to
      surgery. Reoperation was required in 26.7% of patients. Of these, two-thirds had
      combined superior/medial abscesses that re-accumulated after isolated endonasal
      surgery. Two of the 3 patients with profound vision loss had a dental etiology.
      CONCLUSIONS: Only young age, prior antibiotics and degree of restriction
      predicted the presence of an abscess. Re-accumulation was more common than
      anticipated, and drainage of superior/medial abscesses by endoscopic surgery
      alone had the strongest association with surgical failure. Patients with
      odontogenic abscesses must be treated with particular caution.

PMID- 25867949
TI  - Assessing the association between natural food folate intake and blood folate
      concentrations: a systematic review and Bayesian meta-analysis of trials and
      observational studies.
AB  - Folate is found naturally in foods or as synthetic folic acid in dietary
      supplements and fortified foods. Adequate periconceptional folic acid intake can
      prevent neural tube defects. Folate intake impacts blood folate concentration;
      however, the dose-response between natural food folate and blood folate
      concentrations has not been well described. We estimated this association among
      healthy females. A systematic literature review identified studies (1 1992-3
      2014) with both natural food folate intake alone and blood folate concentration
      among females aged 12-49 years. Bayesian methods were used to estimate regression
      model parameters describing the association between natural food folate intake
      and subsequent blood folate concentration. Seven controlled trials and 29
      observational studies met the inclusion criteria. For the six studies using
      microbiologic assay (MA) included in the meta-analysis, we estimate that a 6%
      (95% Credible Interval (CrI): 4%, 9%) increase in red blood cell (RBC) folate
      concentration and a 7% (95% CrI: 1%, 12%) increase in serum/plasma folate
      concentration can occur for every 10% increase in natural food folate intake.
      Using modeled results, we estimate that a natural food folate intake of >= 450
      MUg dietary folate equivalents (DFE)/day could achieve the lower bound of an RBC
      folate concentration (~ 1050 nmol/L) associated with the lowest risk of a neural
      tube defect. Natural food folate intake affects blood folate concentration and
      adequate intakes could help women achieve a RBC folate concentration associated
      with a risk of 6 neural tube defects/10,000 live births.

PMID- 25867950
TI  - Differential acute effects of selenomethionine and sodium selenite on the
      severity of colitis.
AB  - The European population is only suboptimally supplied with the essential trace
      element selenium. Such a selenium status is supposed to worsen colitis while
      colitis-suppressive effects were observed with adequate or supplemented amounts
      of both organic selenomethionine (SeMet) and inorganic sodium selenite. In order
      to better understand the effect of these selenocompounds on colitis development
      we examined colonic phenotypes of mice fed supplemented diets before the onset of
      colitis or during the acute phase. Colitis was induced by treating mice with 1%
      dextran sulfate sodium (DSS) for seven days. The selenium-enriched diets were
      either provided directly after weaning (long-term) or were given to mice with a
      suboptimal selenium status after DSS withdrawal (short-term). While long-term
      selenium supplementation had no effect on colitis development, short-term
      selenite supplementation, however, resulted in a more severe colitis. Colonic
      selenoprotein expression was maximized in all selenium-supplemented groups
      independent of the selenocompound or intervention time. This indicates that the
      short-term selenite effect appears to be independent from colonic selenoprotein
      expression. In conclusion, a selenite supplementation during acute colitis has no
      health benefits but may even aggravate the course of disease. 

PMID- 25867951
TI  - Cytotoxic activity of Piper cubeba extract in breast cancer cell lines.
AB  - This study aimed to evaluate the cytotoxicity of a crude extract of Piper cubeba
      against normal and breast cancer cell lines. To prepare the extract, P. cubeba
      seeds were ground, soaked in methanol and dichloromethane and isolated by column
      chromatography. Fractions were tested for cytotoxicity effects on normal
      fibroblast (L929), normal breast (MCF-12A) and breast cancer cell lines (MCF-7,
      MDA-MB-468 and MDA-MB-231). The most effective fraction was selected for DNA
      fragmentation assay to detect apoptotic activity. The results showed that the
      methanolic crude extract had a higher cytotoxic activity against MDA-MB-468 and
      MCF-7 than a dichloromethane crude extract. Then, the methanolic crude extract
      was separated into six fractions, designated A to F. Fraction C was highly active
      against breast cancer cell lines with an IC50 value less than 4 MUg/mL.
      Therefore, Fraction C was further separated into seven fractions, CA to CG. The
      1H-NMR profile showed that Fraction CE was long chain hydrocarbons. Moreover,
      Fraction CE demonstrated the highest activity against MCF-7 cells with an IC50
      value of 2.69 +/- 0.09 MUg/mL and lower cytotoxicity against normal fibroblast
      L929 cells with an IC50 value of 4.17 +/- 0.77 MUg/mL. Finally, DNA fragmentation
      with a ladder pattern characteristic of apoptosis was observed in MCF-7, MDA-MB
      468, MDA-MB-231 and L929 cells, but not in MCF-12A cells. 

PMID- 25867952
TI  - Consumption and sources of dietary salt in family members in Beijing.
AB  - In China, few people are aware of the amount and source of their salt intake. We
      conducted a survey to investigate the consumption and sources of dietary salt
      using the "one-week salt estimation method" by weighing cooking salt and major
      salt-containing food, and estimating salt intake during dining out based on
      established evidence. Nine hundred and three families (1981 adults and 971
      children) with students in eight primary or junior high schools in urban and
      suburban Beijing were recruited. On average, the daily dietary salt intake of
      family members in Beijing was 11.0 (standard deviation: 6.2) g for children and
      adolescents (under 18 years old), 15.2 (9.1) g for adults (18 to 59 years old),
      and 10.2 (4.8) g for senior citizens (60 years old and over), respectively.
      Overall, 60.5% of dietary salt was consumed at home, and 39.5% consumed outside
      the home. Approximately 90% of the salt intake came from cooking (household
      cooking and cafeteria or restaurant cooking), while less than 10% came from
      processed food. In conclusion, the dietary salt intake in Beijing families far
      surpassed the recommended amounts by World Health Organization, with both
      household cooking and dining-out as main sources of salt consumption. More
      targeted interventions, especially education about major sources of salt and
      corresponding methods for salt reduction should be taken to reduce the risks
      associated with a high salt diet. 

PMID- 25867954
TI  - Effects of interactions of auxin-producing bacteria and bacterial-feeding
      nematodes on regulation of peanut growths.
AB  - The influences of an IAA (indole-3-acetic acid)-producing bacterium (Bacillus
      megaterium) and two bacterial-feeding nematodes (Cephalobus sp. or Mesorhabditis
      sp.) on the growth of peanut (Arachis hypogaea L. cv. Haihua 1) after various
      durations of time were investigated in natural soils. The addition of bacteria
      and nematodes and incubation time all significantly affected plant growth, plant
      root growth, plant nutrient concentrations, soil nutrient concentrations, soil
      microorganisms and soil auxin concentration. The addition of nematodes caused
      greater increases in these indices than those of bacteria, while the addition of
      the combination of bacteria and nematodes caused further increases. After 42-day
      growth, the increases in soil respiration differed between the additions of two
      kinds of nematodes because of differences in their life strategies. The effects
      of the bacteria and nematodes on the nutrient and hormone concentrations were
      responsible for the increases in plant growth. These results indicate the
      potential for promoting plant growth via the addition of nematodes and bacteria
      to soil. 

PMID- 25867953
TI  - The relationship of serum macrophage inhibitory cytokine-1 levels with gray
      matter volumes in community-dwelling older individuals.
AB  - Using circulating inflammatory markers and magnetic resonance imaging (MRI),
      recent studies have associated inflammation with brain volumetric measures.
      Macrophage Inhibitory Cytokine-1 (MIC-1/GDF15) is a divergent transforming growth
      factor - beta (TGF-beta) superfamily cytokine. To uncover the underlying
      mechanisms of the previous finding of a negative association between MIC-1/GDF15
      serum levels and cognition, the present study aimed to examine the relationship
      of circulating MIC-1/GDF15 levels with human brain gray matter (GM) volumes, in a
      community-dwelling sample aged 70-90 years over two years (Wave 1: n = 506, Wave
      2: n = 327), of which the age-related brain atrophy had been previously well
      defined. T1-weighted MRI scans were obtained at both waves and analyzed using the
      FMRIB Software Library and FreeSurfer. The results showed significantly negative
      associations between MIC-1/GDF15 serum levels and both subcortical and cortical
      GM volumes. GM volumes of the whole brain, cortex, temporal lobe, thalamus and
      accumbens showed significant mediating effects on the associations between MIC
      1/GDF15 serum levels and global cognition scores. Increases in MIC-1/GDF15 serum
      levels were associated with decreases in cortical and subcortical GM volume over
      two years. In conclusion, MIC-1/GDF15 serum levels were inversely associated with
      GM volumes both cross-sectionally and longitudinally. 

PMID- 25867955
TI  - In-Situ-Reduced Synthesis of Ti3+ Self-Doped TiO2/g-C3N4 Heterojunctions with
      High Photocatalytic Performance under LED Light Irradiation.
AB  - A simple one-step calcination route was used to prepare Ti(3+) self-doped TiO2/g
      C3N4 heterojunctions by mixture of H2Ti3O7 and melamine. X-ray diffraction (XRD),
      transmission electron microscopy (TEM), high-resolution transmission electron
      microscopy (HRTEM), X-ray photoelectron spectroscopy (XPS), electron spin
      resonance (ESR) spectroscopy, and UV-Vis diffuse reflectance spectroscopy (UV-vis
      DRS) technologies were used to characterize the structure, crystallinity,
      morphology, and chemical state of the as-prepared samples. The absorption of the
      prepared Ti(3+) self-doped TiO2/g-C3N4 heterojunctions shifted to a longer
      wavelength region in comparison with pristine TiO2 and g-C3N4. The photocatalytic
      activities of the heterojunctions were studied by degrading methylene blue under
      a 30 W visible-light-emitting diode irradiation source. The visible-light
      photocatalytic activities enhanced by the prepared Ti(3+) self-doped TiO2/g-C3N4
      heterojunctions were observed and proved to be better than that of pure TiO2 and
      g-C3N4. The photocatalysis mechanism was investigated and discussed. The
      intensive separation efficiency of photogenerated electron-hole in the prepared
      heterojunction was confirmed by photoluminescence (PL) spectra. The removal rate
      constant reached 0.038 min(-1) for the 22.3 wt % Ti(3+) self-doped TiO2/g-C3N4
      heterojunction, which was 26.76 and 7.6 times higher than that of pure TiO2 and g
      C3N4, respectively. The established heterojunction between the interfaces of TiO2
      nanoparticles and g-C3N4 nanosheets as well as introduced Ti(3+) led to the rapid
      electron transfer rate and improved photoinduced electron-hole pair's separation
      efficiency, resulting in the improved photocatalytic performance of the Ti(3+)
      self-doped TiO2/g-C3N4 heterojunctions. 

PMID- 25867956
TI  - A comparative analysis of recombinant protein expression in different
      biofactories: bacteria, insect cells and plant systems.
AB  - Plant-based systems are considered a valuable platform for the production of
      recombinant proteins as a result of their well-documented potential for the
      flexible, low-cost production of high-quality, bioactive products. In this study,
      we compared the expression of a target human recombinant protein in traditional
      fermenter-based cell cultures (bacterial and insect) with plant-based expression
      systems, both transient and stable. For each platform, we described the set-up,
      optimization and length of the production process, the final product quality and
      the yields and we evaluated provisional production costs, specific for the
      selected target recombinant protein. Overall, our results indicate that bacteria
      are unsuitable for the production of the target protein due to its accumulation
      within insoluble inclusion bodies. On the other hand, plant-based systems are
      versatile platforms that allow the production of the selected protein at lower
      costs than Baculovirus/insect cell system. In particular, stable transgenic lines
      displayed the highest-yield of the final product and transient expressing plants
      the fastest process development. However, not all recombinant proteins may
      benefit from plant-based systems but the best production platform should be
      determined empirically with a case-by-case approach, as described here. 

PMID- 25867957
TI  - Glucagon-Secreting Alpha Cell Selective Two-Photon Fluorescent Probe TP-alpha:
      For Live Pancreatic Islet Imaging.
AB  - Two-photon (TP) microscopy has an advantage for live tissue imaging which allows
      a deeper tissue penetration up to 1 mm comparing to one-photon (OP) microscopy.
      While there are several OP fluorescence probes in use for pancreatic islet
      imaging, TP imaging of selective cells in live islet still remains a challenge.
      Herein, we report the discovery of first TP live pancreatic islet imaging probe;
      TP-alpha (Two Photon-alpha) which can selectively stain glucagon secreting alpha
      cells. Through fluorescent image based screening using three pancreatic cell
      lines, we discovered TP-alpha from a TP fluorescent dye library TPG (TP-Green).
      In vitro fluorescence test showed that TP-alpha have direct interaction and
      appear glucagon with a significant fluorescence increase, but not with insulin or
      other hormones/analytes. Finally, TP-alpha was successfully applied for 3D
      imaging of live islets by staining alpha cell directly. The newly developed TP
      alpha can be a practical tool to evaluate and identify live alpha cells in terms
      of localization, distribution and availability in the intact islets. 

PMID- 25867958
TI  - Athymic rat model for evaluation of engineered anterior cruciate ligament grafts.
AB  - Anterior cruciate ligament (ACL) rupture is a common ligamentous injury that
      often requires surgery because the ACL does not heal well without intervention.
      Current treatment strategies include ligament reconstruction with either
      autograft or allograft, which each have their associated limitations. Thus, there
      is interest in designing a tissue-engineered graft for use in ACL reconstruction.
      We describe the fabrication of an electrospun polymer graft for use in ACL tissue
      engineering. This polycaprolactone graft is biocompatible, biodegradable, porous,
      and is comprised of aligned fibers. Because an animal model is necessary to
      evaluate such a graft, this paper describes an intra-articular athymic rat model
      of ACL reconstruction that can be used to evaluate engineered grafts, including
      those seeded with xenogeneic cells. Representative histology and biomechanical
      testing results at 16 weeks postoperatively are presented, with grafts tested
      immediately post-implantation and contralateral native ACLs serving as controls.
      The present study provides a reproducible animal model with which to evaluate
      tissue engineered ACL grafts, and demonstrates the potential of a regenerative
      medicine approach to treatment of ACL rupture. 

PMID- 25867959
TI  - Nestable Tetrakis(spiroborate) Nanocycles.
AB  - Multicomponent construction of the tetrakis(spiroborate) anionic nanocycles was
      achieved by reacting bis(dihydroxynaphthalene)s with tetrahydroxyanthraquinone in
      the presence of boric acid in a self-organized manner. These nanocycles exhibited
      selective molecular recognition behavior toward cationic guests such as methyl
      viologen derivatives. Formation of a supramolecular ring@ring and a
      guest@ring@ring structure was observed by combining the anionic nanocycle and the
      vinylogous analog of cyclobis(paraquat-p-phenylene). 

PMID- 25867960
TI  - The forced swim test as a model of depressive-like behavior.
AB  - The goal of the present protocol is to describe the forced swim test (FST), which
      is one of the most commonly used assays for the study of depressive-like behavior
      in rodents. The FST is based on the assumption that when placing an animal in a
      container filled with water, it will first make efforts to escape but eventually
      will exhibit immobility that may be considered to reflect a measure of behavioral
      despair. This test has been extensively used because it involves the exposure of
      the animals to stress, which was shown to have a role in the tendency for major
      depression. Additionally, the FST has been shown to share some of the factors
      that are influenced or altered by depression in humans, including changes in food
      consumption, sleep abnormalities and drug-withdrawal-induced anhedonia. The main
      advantages of this procedure are that it is relatively easy to perform and that
      its results are easily and quickly analyzed. Moreover, its sensitivity to a broad
      range of antidepressant drugs that makes it a suitable screening test is one of
      the most important features leading to its high predictive validity. Despite its
      appeal, this model has a number of disadvantages. First, the issue of chronic
      augmentation is problematic in this test because in real life patients need to be
      treated for at least several weeks before they experience any relief from their
      symptoms. Last, due to the aversiveness of the FST, it is important to take into
      account possible influences it might have on brain structure/function if brain
      analyses are to be carried out following this procedure. 

PMID- 25867961
TI  - Preoperative beta-cell function in patients with type 2 diabetes is important for
      the outcome of Roux-en-Y gastric bypass surgery.
AB  - The majority of the patients with type 2 diabetes (T2DM) show remission after
      Roux-en-Y gastric bypass (RYGB). This is the result of increased postoperative
      insulin sensitivity and beta-cell secretion. The aim of the present study was to
      elucidate the importance of the preoperative beta-cell function in T2DM for the
      chance of remission after RYGB. Fifteen patients with and 18 without T2DM had 25
      g oral (OGTT) and intravenous (IVGTT) glucose tolerance tests performed at
      inclusion, after a diet-induced weight loss, and 4 and 18 months after RYGB.
      Postoperative first phase insulin secretion rate (ISR) during the IVGTT and beta
      cell glucose sensitivity during the OGTT increased in T2DM. Postoperative insulin
      sensitivity and the disposition index (DI) markedly increased in both groups. By
      stratifying the T2DM into two groups according to highest (T2DMhigh ) and lowest
      (T2DMlow ) baseline DI, a restoration of first phase ISR and beta-cell glucose
      sensitivity were seen only in T2DMhigh . Remission of type 2 diabetes was 71 and
      38% in T2DMhigh and T2DMlow , respectively. Postoperative postprandial GLP-1
      concentrations increased markedly, but did not differ between the groups. Our
      findings emphasize the importance of the preoperative of beta-cell function for
      remission of diabetes after RYGB.

PMID- 25867962
TI  - Implicit processing of heroin and emotional cues in abstinent heroin users: early
      and late event-related potential effects.
AB  - BACKGROUND: The abnormal cognitive processing of drug cues is a core
      characteristic of drug dependence. Previous research has suggested that the late
      positive potential (LPP) of heroin users is increased by heroin-related stimuli
      because of the attention-grabbing nature of such stimuli. OBJECTIVES: The present
      research used a modified emotional Stroop (eStroop) task to examine whether there
      was an early posterior negativity (EPN) modulation to heroin cues compared with
      emotional or neutral stimuli in heroin dependent subjects. METHODS: Fifteen
      former heroin users and 15 matched controls performed the eStroop task, which was
      composed of positive, negative, heroin-related, and neutral pictures with
      superimposed color squares. Participants responded to the color of the square and
      not to the picture while behavioral data and event-related potentials were
      recorded. RESULTS: There were no significant differences of EPN amplitudes to
      emotional and neutral stimuli between heroin users and controls. However, heroin
      users displayed increased EPN modulation for heroin cues, whereas this modulation
      was absent in controls. CONCLUSIONS: Drug-related cues acquire motivational
      salience and automatically capture the attention of heroin users at early
      processing stages, even when engaged in a non-drug-related task. The EPN to
      heroin cues could represent a novel electrophysiological index with clinical
      implications for selecting abstinent drug users who are at increased risk of
      relapse or to evaluate treatment interventions.

PMID- 25867963
TI  - Pretest prediction and diagnosis of metastatic lesions to the pancreas by
      endoscopic ultrasound-guided fine needle aspiration.
AB  - BACKGROUND AND AIM: Early diagnosis of solid pancreatic lesions (SPLs) enables
      prompt treatment. The study aims to identify factors differentiating metastatic
      lesion to the pancreas (PMET) from pancreatic ductal adenocarcinoma (PDAC) and
      pancreatic neuroendocrine tumors (PNETs). METHODS: This is a retrospective study
      at a tertiary cancer center. Consecutive patients referred for endoscopic
      ultrasound (EUS) of SPLs from 2004 to 2011 were reviewed. The main outcomes were
      pre-EUS-FNA (endoscopic ultrasound-guided fine needle aspiration) predictors and
      diagnostic accuracy of EUS-FNA for PMETs. RESULTS: Among a total of 1108 EUS-FNAs
      for pancreatic lesions, 672 patients had neoplastic SPLs (PMETs = 53; PDACs =
      528, PNETs = 91). The sensitivity, specificity, positive predictive value, and
      accuracy of EUS-FNA for diagnosis of PMETs were 84.9%, 100%, 100%, and 98.8%,
      respectively. The mean number of EUS-FNA passes for diagnosis of PMET was 3.1 per
      patient. For each endosonographer, preceding 3-year EUS volume (mean/year)
      significantly correlated with fewer needle passes (rs [-0.30], P = 0.03). The
      most common PMET was renal cell carcinoma. Stratified multivariate analyses were
      performed. Compared with patients with PDACs, PMETs were more common in men (odds
      ratio [OR] = 2.0; 95% confidence interval [CI] = 1.0-4.0); located in the
      pancreatic tail (OR = 2.4; 95%CI = 1.1-5.2); and were less likely with increasing
      age (OR = 0.95; 95%CI = 0.92-0.99), presence of major symptoms (abdomen
      pain/diarrhea/weight loss; OR = 0.2; 95%CI = 0.1-0.4), elevated bilirubin (OR =
      0.3; 95%CI = 0.13-0.69), and imaging evidence of arterial invasion (OR = 0.15;
      95%CI = 0.03-0.67). Compared with PNETs, PMETs were more common with increase age
      (OR = 1.05; 95%CI = 1.02-1.08) and increasing lesion size (OR = 1.03; 95%CI = 1.0
      1.1), and were less likely in patients with diabetes (OR = 0.34; 95%CI = 0.11
      0.99). CONCLUSION: Among the largest numbers of neoplastic SPLs evaluated at a
      single center, pre-test features reliably characterize, and EUS-FNA provides a
      highly specific diagnosis of PMETs.

PMID- 25867964
TI  - Topcoat-Assisted Perpendicular and Straightly Parallel Coexisting Orientations of
      Block Copolymer Films.
AB  - Highly ordered perpendicular orientation and straightly parallel orientation
      coexisting polystyrene-block-polydimethylsiloxane (PS-b-PDMS) cylindrical
      microdomains with 10 nm width can be realized by using polyvinyl acetate as a
      partially dewetted topcoat and solvent annealing with acetone vapor. During
      solvent annealing, the swelled topcoat begins to dewet and the dewetting rim
      sweeps the surface of the block copolymer films to align the cylindrical
      microdomains with the direction of dewetting propagation. However, the wetted
      region of the topcoat/PS-b-PDMS film forms with a perpendicular orientation due
      to reduced surface tension and sufficient concentration gradient in the solvent
      evaporation step. The orientational changes (perpendicular/straightly parallel
      orientation) in the dewetted/wetted area are also investigated according to the
      vapor pressure of solvent annealing. The degree of directionality of the swept PS
      b-PDMS films according to the distance from the dewetting front, which is
      equivalent with time after sweeping, is examined. To control the direction of
      dewetting and complex structures within a specific area, an imprinting process is
      introduced to form topographical line-space patterns in the topcoat and
      perpendicular/parallel orientation of BCP patterns in the line-space patterns,
      respectively. 

PMID- 25867965
TI  - HIF-inducible miR-191 promotes migration in breast cancer through complex
      regulation of TGFbeta-signaling in hypoxic microenvironment.
AB  - The molecular mechanisms of hypoxia induced breast cell migration remain
      incompletely understood. Our results show that hypoxia through hypoxia-inducible
      factor (HIF) brings about a time-dependent increase in the level of an oncogenic
      microRNA, miR-191 in various breast cancer cell lines. miR-191 enhances breast
      cancer aggressiveness by promoting cell proliferation, migration and survival
      under hypoxia. We further established that miR-191 is a critical regulator of
      transforming growth factor beta (TGFbeta)-signaling and promotes cell migration
      by inducing TGFbeta2 expression under hypoxia through direct binding and
      indirectly by regulating levels of a RNA binding protein, human antigen R (HuR).
      The levels of several TGFbeta pathway genes (like VEGFA, SMAD3, CTGF and BMP4)
      were found to be higher in miR-191 overexpressing cells. Lastly, anti-miR-191
      treatment given to breast tumor spheroids led to drastic reduction in spheroid
      tumor volume. This stands as a first report of identification of a microRNA
      mediator that links hypoxia and the TGFbeta signaling pathways, both of which are
      involved in regulation of breast cancer metastasis. Together, our results show a
      critical role of miR-191 in hypoxia-induced cancer progression and suggest that
      miR-191 inhibition may offer a novel therapy for hypoxic breast tumors. 

PMID- 25867966
TI  - Hearing loss in palliative care.
AB  - BACKGROUND: Age-related hearing loss is remarkably common, affecting more than
      60% of adults over the age of 75. Moreover, hearing loss has detrimental effects
      on quality of life and communication, outcomes that are central to palliative
      care. Despite its high prevalence, there is remarkably little written on the
      impact of hearing loss in the palliative care literature. OBJECTIVE: The
      objective was to emphasize its importance and the need for further study. We use
      a case as a springboard for discussing what is known and unknown about the
      epidemiology, presentation, screening methodologies, and treatment strategies for
      age-related hearing loss in palliative care. DISCUSSION: The case describes a 65
      year-old man with acute myelogenous leukemia (AML) that has progressed despite
      treatment. No concerns are raised about communication challenges during
      conversations between the palliative care team and the patient in his quiet room.
      However, in the midst of a family meeting, shortly after discussing prognosis,
      the patient reports that he cannot hear what anyone is saying. CONCLUSION: We
      describe simple methods of screening patients for hearing loss, and suggest that
      practical approaches should be used universally in patient encounters. These
      include facing the patient, pitching one's voice low, using a pocket talker, and
      creating a hearing-friendly environment when planning a family or group meeting.

PMID- 25867967
TI  - New ways, new moves: treatment of children with disabilities.

PMID- 25867968
TI  - Think 'neurodevelopmental syndrome'.

PMID- 25867969
TI  - A simple and inexpensive method for determining cold sensitivity and adaptation
      in mice.
AB  - Cold hypersensitivity is a serious clinical problem, affecting a broad subset of
      patients and causing significant decreases in quality of life. The cold plantar
      assay allows the objective and inexpensive assessment of cold sensitivity in
      mice, and can quantify both analgesia and hypersensitivity. Mice are acclimated
      on a glass plate, and a compressed dry ice pellet is held against the glass
      surface underneath the hindpaw. The latency to withdrawal from the cooling glass
      is used as a measure of cold sensitivity. Cold sensation is also important for
      survival in regions with seasonal temperature shifts, and in order to maintain
      sensitivity animals must be able to adjust their thermal response thresholds to
      match the ambient temperature. The Cold Plantar Assay (CPA) also allows the study
      of adaptation to changes in ambient temperature by testing the cold sensitivity
      of mice at temperatures ranging from 30  degrees C to 5  degrees C. Mice are
      acclimated as described above, but the glass plate is cooled to the desired
      starting temperature using aluminum boxes (or aluminum foil packets) filled with
      hot water, wet ice, or dry ice. The temperature of the plate is measured at the
      center using a filament T-type thermocouple probe. Once the plate has reached the
      desired starting temperature, the animals are tested as described above. This
      assay allows testing of mice at temperatures ranging from innocuous to noxious.
      The CPA yields unambiguous and consistent behavioral responses in uninjured mice
      and can be used to quantify both hypersensitivity and analgesia. This protocol
      describes how to use the CPA to measure cold hypersensitivity, analgesia, and
      adaptation in mice. 

PMID- 25867971
TI  - Levels of F2 isoprostane in Behcet's disease: Correlation with cardiometabolic
      risk factors.
AB  - OBJECTIVE: Behcet's disease (BD) is a chronic inflammatory disease and recent
      findings suggest a role of oxidative stress in the pathogenesis of BD. Free
      radical-induced oxidative stress is also involved in the pathogenesis of
      cardiovascular and other rheumatic diseases. Oxidative stress may be detected in
      vivo by measuring F2 isoprostanes. Here, we measured plasma levels of F2
      isoprostane in patients with BD and evaluated the correlation of F2 isoprostane
      with cardiometabolic risk factors. METHODS: Forty-three patients with BD in
      remission and 37 age- and sex-matched controls were recruited for the study.
      Blood samples were obtained to determine F2 isoprostane, C-reactive protein
      levels, erythrocyte sedimentation rate, and other biochemical parameters.
      Homeostasis model assessment insulin resistance and body mass index were
      calculated. Systolic blood pressure, diastolic blood pressure, and waist
      circumference were measured. RESULTS: Plasma F2 isoprostane, fasting plasma
      glucose, triglyceride, and C-reactive protein levels were significantly higher in
      patients with BD compared with healthy controls, whereas high-density lipoprotein
      cholesterol levels were significantly lower in patients with BD. F2 isoprostane
      levels did not correlate with cardiometabolic risk factors, C-reactive protein
      levels, or erythrocyte sedimentation rate. CONCLUSION: High levels of F2
      isoprostane in patients with BD indicate oxidative stress. Antioxidant
      therapeutic approaches could potentially affect the course of this disease.

PMID- 25867970
TI  - Sex differences in the association between depression, anxiety, and type 2
      diabetes mellitus.
AB  - BACKGROUND: Depression and anxiety have been inconsistently associated with
      diabetes. Sex differences in the biological and behavioral correlates of these
      forms of distress could partially explain these inconsistencies. We investigated
      sex-specific associations between depression/anxiety symptoms and diabetes in two
      separate samples. METHODS: The First National Health and Nutrition Examination
      Survey enrolled 3233 participants aged 25 to 74 years from 1971 to 1974.
      Depression and anxiety symptoms were measured via General Well Being schedule
      subscales. Incident diabetes for 17 years was defined by the following: a) death
      certificate, b) participant self-report, or c) health care facility discharge.
      The Detroit Neighborhood Health Study enrolled 1054 participants 18 years or
      older from 2008 to 2010. The Patient Health Questionnaire-9 and Generalized
      Anxiety Disorder-7 assessed depression and anxiety. Participants' self-reported
      physician-diagnosed prevalent diabetes. RESULTS: In the First National Health and
      Nutrition Examination Survey, the risk ratio (RR; 95% confidence interval) for
      incident diabetes among men with high versus low anxiety symptoms was 0.85 (0.56
      1.29) and that among women was 2.19 (1.17-4.09; p for interaction = .005). RRs
      comparing high versus low depressive symptoms for men and women were 0.69 (0.43
      1.100) and 2.11 (1.06-4.19); p for interaction = .007. In the Detroit
      Neighborhood Health Study, the RRs for prevalent diabetes comparing those with
      high versus low anxiety symptoms were 0.24 (0.02-2.42) for men and 1.62 (0.61
      4.32) for women (p for interaction = < .001), whereas RRs for depression were
      1.30 (0.46-3.68) for men and 2.32 (1.10-4.89) for women (p for interaction =
      .16). CONCLUSIONS: In two separate samples, depressive symptoms were related to
      increased diabetes risk among women but not men. Although less robust, findings
      for anxiety were differentially associated with diabetes by sex.

PMID- 25867972
TI  - Nanostructure and salt effect of zwitterionic carboxybetaine brush at the
      air/water interface.
AB  - Zwitterionic amphiphilic diblock copolymer, poly(ethylhexyl acrylate)-b
      poly(carboxybetaine) (PEHA-b-PGLBT), was synthesized by the reversible addition
      fragmentation chain transfer (RAFT) method with precise control of block length
      and polydispersity. The polymers thus obtained were spread onto the water surface
      to form a polymer monolayer. The fundamental property and nanostructure of the
      block copolymer monolayer were systematically studied by the surface pressure
      molecular area (pi-A) isotherm, Brewster angle microscopy (BAM), and X-ray
      reflectivity (XR) techniques. The pi values of the monolayer increased by
      compression in relatively larger A regions. After showing a large plateau region
      by compression, the pi value sharply increased at very small A regions,
      suggesting the formation of poly(GLBT) brush formation just beneath the water
      surface. The domain structure of MUm size was observed by BAM in the plateau
      region. XR profiles for the monolayer at higher surface pressure regions clearly
      showed the PGLBT brush formation in addition to PGLBT carpet layer formation
      under the hydrophobic PEHA layer on the water surface, as was observed for both
      anionic and cationic brush layer in the water surface monolayer studied
      previously. The critical brush density, where the PGLBT brush is formed, was
      estimated to be about 0.30 chains/nm(2) for the (EHA)45-b-(GLBT)60 monolayer,
      which is relatively large compared to other ionic brushes. This observation is
      consistent with the fact that the origin of brush formation is mainly steric
      hindrance between brush chains. The brush thickness increased by compression and
      also by salt addition, unlike the normal ionic brush (anionic and cationic),
      whose thickness tended to decrease, i.e., shrink, by salt addition. This might be
      a character unique to the zwitterionic brush, and its origin is thought to be
      transition to an ionic nature from the almost nonionic inner salt caused by salt
      addition since both the cation and anion of the GLBT chain obtained counterions
      by the addition of salt. This stretching nature of the PGLBT brush depends on the
      ion species of the salt added, and it followed the Hofmeister series, i.e., more
      stretching in the order of Li(+) > Na(+) > K(+). However, it was rather
      insensitive to the anion species (Cl(-), Br(-), SCN(-)), which suggests that the
      carboxylic anion has a more dominant effect than the quaternized cation in GLBT
      although the former is a weak acid and the latter is believed to be a strong
      base. 

PMID- 25867974
TI  - Out-of-Phase Electron Spin Echo Studies of Light-Induced Charge-Transfer States
      in P3HT/PCBM Composite.
AB  - The light-induced charge-transfer (CT) state in the composite of the conductive
      polymer poly(3-hexylthiophene) (P3HT) and the fullerene derivative [6,6]-phenyl
      C61-butyric acid methyl ester (PCBM) has been studied by electron spin echo (ESE)
      spectroscopy. The out-of-phase ESE signal corresponding to the spin-correlated
      radical pair P3HT(+)/PCBM(-) has been observed in this composite material. The
      time-domain ESE shape for different delays between the laser flash and the
      microwave pulse sequence has been analyzed. In order to explain the evolution of
      the out-of-phase ESE signal as a function of the delay between the microwave
      pulses, a model of the CT state is proposed. The hole is assumed to be
      delocalized on the P3HT chain over several thiophene subunits, while the point
      dipole approximation is used to describe the interaction with the electron on
      PCBM. The distribution of distances between the positive and negative charges in
      the CT state has been evaluated. 

PMID- 25867973
TI  - Genetic variants in matrix metalloproteinase genes as disposition factors for
      ovarian cancer risk, survival, and clinical outcome.
AB  - Ovarian cancer is one of the leading female cancers in the United States.
      Challenges remain in early diagnosis of this deadly disease. Matrix
      metalloproteinases (MMPs) family genes are paradoxically involved in cancer
      promotion and suppression. We hypothesize that genetic variants in MMP genes are
      associated with ovarian cancer development, so they could be potential markers
      for ovarian cancer diagnosis and prognosis. In this study of 417 ovarian cancer
      cases and 417 healthy controls, we genotyped a comprehensive panel of 266 single
      nucleotide polymorphisms (SNPs) in 23 MMP genes and analysed their associations
      with ovarian cancer risk, overall survival and treatment response in ovarian
      cancer cases who received platinum-based chemotherapy with surgery. In the
      analysis on 339 Caucasian cases and 349 Caucasian controls, 4 SNPs were
      significantly associated with cancer risk. The most significant association was
      observed for rs2292730 (OR = 2.03, 95% CI = 1.39-2.96, P = 0.0002).
      Classification and regression tree analysis identified four terminal nodes with
      differential risk of ovarian cancer. Thirty-four SNPs were significantly
      associated with overall survival and four of which showed significant association
      with response to chemotherapy. Unfavourable genotype analysis of top SNPs on
      overall risk of death showed significant gene-dosage effect, survival tree
      analysis differentiated patients into distinct risk groups based on their genetic
      profiles with median survival times (MSTs) ranging from 17.7 to 151.7 months. In
      conclusion, our results suggest that genetic variants in MMP pathway genes may
      modulate the risk and clinical outcomes of ovarian cancer, both individually and
      jointly.

PMID- 25867977
TI  - Multiple functions of gingival and mucoperiosteal fibroblasts in oral wound
      healing and repair.
AB  - Fibroblasts are cells of mesenchymal origin. They are responsible for the
      production of most extracellular matrix in connective tissues and are essential
      for wound healing and repair. In recent years, it has become clear that
      fibroblasts from different tissues have various distinct traits. Moreover, wounds
      in the oral cavity heal under very special environmental conditions compared with
      skin wounds. Here, we reviewed the current literature on the various
      interconnected functions of gingival and mucoperiosteal fibroblasts during the
      repair of oral wounds. The MEDLINE database was searched with the following
      terms: (gingival OR mucoperiosteal) AND fibroblast AND (wound healing OR repair).
      The data gathered were used to compare oral fibroblasts with fibroblasts from
      other tissues in terms of their regulation and function during wound healing.
      Specifically, we sought answers to the following questions: (i) what is the role
      of oral fibroblasts in the inflammatory response in acute wounds; (ii) how do
      growth factors control the function of oral fibroblasts during wound healing;
      (iii) how do oral fibroblasts produce, remodel and interact with extracellular
      matrix in healing wounds; (iv) how do oral fibroblasts respond to mechanical
      stress; and (v) how does aging affect the fetal-like responses and functions of
      oral fibroblasts? The current state of research indicates that oral fibroblasts
      possess unique characteristics and tightly controlled specific functions in wound
      healing and repair. This information is essential for developing new strategies
      to control the intraoral wound-healing processes of the individual patient. 

PMID- 25867978
TI  - In vitro models for evaluation of periodontal wound healing/regeneration.
AB  - Periodontal wound healing and regeneration are highly complex processes,
      involving cells, matrices, molecules and genes that must be properly
      choreographed and orchestrated. As we attempt to understand and influence these
      clinical entities, we need experimental models to mimic the various aspects of
      human wound healing and regeneration. In vivo animal models that simulate
      clinical situations of humans can be costly and cumbersome. In vitro models have
      been devised to dissect wound healing/regeneration processes into discrete,
      analyzable steps. For soft tissue (e.g. gingival) healing, in vitro models range
      from simple culture of cells grown in monolayers and exposed to biological
      modulators or physical effectors and materials, to models in which cells are
      'injured' by scraping and subsequently the 'wound' is filled with new or
      migrating cells, to three-dimensional models of epithelial-mesenchymal
      recombination or tissue explants. The cells employed are gingival keratinocytes,
      fibroblasts or endothelial cells, and their proliferation, migration, attachment,
      differentiation, survival, gene expression, matrix production or capillary
      formation are measured. Studies of periodontal regeneration also include
      periodontal ligament fibroblasts or progenitors, osteoblasts or osteoprogenitors,
      and cementoblasts. Regeneration models measure cellular proliferation, attachment
      and migration, as well as gene expression, transfer and differentiation into a
      mineralizing phenotype and biomineralization. Only by integrating data from
      models on all levels (i.e. a single cell to the whole organism) can various
      critical aspects of periodontal wound healing/regeneration be fully evaluated. 

PMID- 25867976
TI  - Wound models for periodontal and bone regeneration: the role of biologic
      research.
AB  - The ultimate goals of periodontal therapy remain the complete regeneration of
      those periodontal tissues lost to the destructive inflammatory-immune response,
      or to trauma, with tissues that possess the same structure and function, and the
      re-establishment of a sustainable health-promoting biofilm from one characterized
      by dysbiosis. This volume of Periodontology 2000 discusses the multiple facets of
      a transition from therapeutic empiricism during the late 1960s, toward
      regenerative therapies, which is founded on a clearer understanding of the
      biophysiology of normal structure and function. This introductory article
      provides an overview on the requirements of appropriate in vitro laboratory
      models (e.g. cell culture), of preclinical (i.e. animal) models and of human
      studies for periodontal wound and bone repair. Laboratory studies may provide
      valuable fundamental insights into basic mechanisms involved in wound repair and
      regeneration but also suffer from a unidimensional and simplistic approach that
      does not account for the complexities of the in vivo situation, in which multiple
      cell types and interactions all contribute to definitive outcomes. Therefore,
      such laboratory studies require validatory research, employing preclinical models
      specifically designed to demonstrate proof-of-concept efficacy, preliminary
      safety and adaptation to human disease scenarios. Small animal models provide the
      most economic and logistically feasible preliminary approaches but the outcomes
      do not necessarily translate to larger animal or human models. The advantages and
      limitations of all periodontal-regeneration models need to be carefully
      considered when planning investigations to ensure that the optimal design is
      adopted to answer the specific research question posed. Future challenges lie in
      the areas of stem cell research, scaffold designs, cell delivery and choice of
      growth factors, along with research to ensure appropriate gingival coverage in
      order to prevent gingival recession during the healing phase. 

PMID- 25867979
TI  - Pre-clinical in vivo models for the screening of bone biomaterials for
      oral/craniofacial indications: focus on small-animal models.
AB  - Preclinical in vivo experimental studies are performed for evaluating proof-of
      principle concepts, safety and possible unwanted reactions of candidate bone
      biomaterials before proceeding to clinical testing. Specifically, models
      involving small animals have been developed for screening bone biomaterials for
      their potential to enhance bone formation. No single model can completely
      recreate the anatomic, physiologic, biomechanic and functional environment of the
      human mouth and jaws. Relevant aspects regarding physiology, anatomy, dimensions
      and handling are discussed in this paper to elucidate the advantages and
      disadvantages of small-animal models. Model selection should be based not on the
      'expertise' or capacities of the team, but rather on a scientifically solid
      rationale, and the animal model selected should reflect the question for which an
      answer is sought. The rationale for using heterotopic or orthotopic testing
      sites, and intraosseous, periosseous or extraskeletal defect models, is
      discussed. The paper also discusses the relevance of critical size defect
      modeling, with focus on calvarial defects in rodents. In addition, the rabbit
      sinus model and the capsule model in the rat mandible are presented and discussed
      in detail. All animal experiments should be designed with care and include sample
      size and study-power calculations, thus allowing generation of meaningful data.
      Moreover, animal experiments are subject to ethical approval by the relevant
      authority. All procedures and the postoperative handling and care, including
      postoperative analgesics, should follow best practice. 

PMID- 25867981
TI  - Wound healing following surgical and regenerative periodontal therapy.
AB  - Clinical studies have evaluated the effect of conventional periodontal surgical
      therapy. In general, although some clinical gain in tissue support may be
      attained, these therapies do not support regeneration of the periodontal
      attachment. Even though the biological possibility of periodontal regeneration
      has been demonstrated, the clinical application of this intrinsic potential
      appears difficult to harness; thus also conceptually most intriguing candidate
      protocols face clinical challenges. In this review, we explore the bioclinical
      principles, condiciones sine quibus non, that unleash the innate potential of the
      periodontium to achieve clinically meaningful periodontal regeneration (i.e.
      space-provision, wound stability and conditions for primary intention healing).
      Moreover, limiting factors and detrimental practices that may compromise clinical
      and biological outcomes are reviewed, as is tissue management in clinical
      settings. 

PMID- 25867982
TI  - Experimental models for guided bone regeneration in healthy and medically
      compromised conditions.
AB  - The increased use of dental implants and related bone-augmentation procedures
      creates a need for reliable proof-of-principle preclinical models for evaluating
      different bone-regenerative techniques. The simulation of clinical scenarios by
      such models is of importance when the experiments are designed in order for the
      outcomes to provide basic points of clinical relevance. At the same time, the
      increased proportion of the population with different chronic diseases of ageing
      necessitates the need to reproduce these conditions in the same proof-of
      principle preclinical models to allow evaluation of the effect of the relevant
      chronic disease on the bone-healing process. This review presents a number of
      'proof-of-principle' preclinical models in health and in chronic systemic
      conditions in which the guided bone regeneration principle was evaluated. 

PMID- 25867983
TI  - Alveolar socket healing: what can we learn?
AB  - Tooth extraction induces a series of complex and integrated local changes within
      the investing hard and soft tissues. These local alterations arise in order to
      close the socket wound and to restore tissue homeostasis, and are referred to as
      '"socket healing". The aims of the present report were twofold: first, to
      describe the socket-healing process; and, second, to discuss what can be learned
      from the temporal sequence of healing events, in order to improve treatment
      outcomes. The socket-healing process may be divided into three sequential, and
      frequently overlapping, phases: inflammatory; proliferative; and
      modeling/remodeling. Several clinical and experimental studies have demonstrated
      that the socket-healing process promotes up to 50% reduction of the original
      ridge width, greater bone resorption at the buccal aspect than at the
      lingual/palatal counterpart and a larger amount of alveolar bone reduction in the
      molar region. In conclusion, tooth extraction, once a simple and straightforward
      surgical procedure, should be performed in the knowledge that ridge reduction
      will follow and that further clinical steps should be considered to compensate
      for this, when considering future options for tooth replacement. 

PMID- 25867980
TI  - Animal models for periodontal regeneration and peri-implant responses.
AB  - Translation of experimental data to the clinical setting requires the safety and
      efficacy of such data to be confirmed in animal systems before application in
      humans. In dental research, the animal species used is dependent largely on the
      research question or on the disease model. Periodontal disease and, by analogy,
      peri-implant disease, are complex infections that result in a tissue-degrading
      inflammatory response. It is impossible to explore the complex pathogenesis of
      periodontitis or peri-implantitis using only reductionist in-vitro methods. Both
      the disease process and healing of the periodontal and peri-implant tissues can
      be studied in animals. Regeneration (after periodontal surgery), in response to
      various biologic materials with potential for tissue engineering, is a continuous
      process involving various types of tissue, including epithelia, connective
      tissues and alveolar bone. The same principles apply to peri-implant healing.
      Given the complexity of the biology, animal models are necessary and serve as the
      standard for successful translation of regenerative materials and dental implants
      to the clinical setting. Smaller species of animal are more convenient for
      disease-associated research, whereas larger animals are more appropriate for
      studies that target tissue healing as the anatomy of larger animals more closely
      resembles human dento-alveolar architecture. This review focuses on the animal
      models available for the study of regeneration in periodontal research and
      implantology; the advantages and disadvantages of each animal model; the
      interpretation of data acquired; and future perspectives of animal research, with
      a discussion of possible nonanimal alternatives. Power calculations in such
      studies are crucial in order to use a sample size that is large enough to
      generate statistically useful data, whilst, at the same time, small enough to
      prevent the unnecessary use of animals. 

PMID- 25867984
TI  - Temporal sequence of hard and soft tissue healing around titanium dental
      implants.
AB  - The objective of the present review was to summarize the evidence available on
      the temporal sequence of hard and soft tissue healing around titanium dental
      implants in animal models and in humans. A search was undertaken to find animal
      and human studies reporting on the temporal dynamics of hard and soft tissue
      integration of titanium dental implants. Moreover, the influence of implant
      surface roughness and chemistry on the molecular mechanisms associated with
      osseointegration was also investigated. The findings indicated that the
      integration of titanium dental implants into hard and soft tissue represents the
      result of a complex cascade of biological events initiated by the surgical
      intervention. Implant placement into alveolar bone induces a cascade of healing
      events starting with clot formation and continuing with the maturation of bone in
      contact with the implant surface. From a genetic point of view, osseointegration
      is associated with a decrease in inflammation and an increase in osteogenesis-,
      angiogenesis- and neurogenesis-associated gene expression during the early stages
      of wound healing. The attachment and maturation of the soft tissue complex (i.e.
      epithelium and connective tissue) to implants becomes established 6-8 weeks
      following surgery. Based on the findings of the present review it can be
      concluded that improved understanding of the mechanisms associated with
      osseointegration will provide leads and targets for strategies aimed at enhancing
      the clinical performance of titanium dental implants. 

PMID- 25867985
TI  - Wound healing in immediately loaded implants.
AB  - The orthopedic field has accumulated ample evidence that bone formation is
      related to functional loading and in general to physical activity. However,
      despite evidence that immediately loaded implants can be predictably successful,
      many clinicians still use the classical (delayed loading) treatment protocol.
      This paper examines the effects of loading on dental implants and discusses the
      advantages of immediate loading. The role of loading on augmented alveolar ridges
      is also addressed and provides evidence that early bone resorption may be
      controlled when bone is functionally loaded. Similar data are emerging for
      advanced augmentation techniques in order to control crestal bone loss. 

PMID- 25867986
TI  - Animal models for peri-implant mucositis and peri-implantitis.
AB  - The treatment of infectious diseases affecting osseointegrated implants in
      function has become a demanding issue in implant dentistry. Since the early
      1990s, preclinical data from animal studies have provided important insights into
      the etiology, pathogenesis and therapy of peri-implant diseases. Established
      lesions in animals have shown many features in common with those found in human
      biopsy material. The current review focuses on animal studies, employing
      different models to induce peri-implant mucositis and peri-implantitis. 

PMID- 25867987
TI  - Biomaterials for promoting periodontal regeneration in human intrabony defects: a
      systematic review.
AB  - Intrabony periodontal defects are a frequent complication of periodontitis and,
      if left untreated, may negatively affect long-term tooth prognosis. The optimal
      outcome of treatment in intrabony defects is considered to be the absence of
      bleeding on probing, the presence of shallow pockets associated with periodontal
      regeneration (i.e. formation of new root cementum with functionally orientated
      inserting periodontal ligament fibers connected to new alveolar bone) and no soft
      tissue recession. A plethora of different surgical techniques, often including
      implantation of various types of bone graft and/or bone substitutes, root surface
      demineralization, guided tissue regeneration, growth and differentiation factors,
      enamel matrix proteins or various combinations thereof, have been employed to
      achieve periodontal regeneration. Despite positive observations in animal models
      and successful outcomes reported for many of the available regenerative
      techniques and materials in patients, including histologic reports, robust
      information on the degree to which reported clinical improvements reflect true
      periodontal regeneration does not exist. Thus, the aim of this review was to
      summarize, in a systematic manner, the available histologic evidence on the
      effect of reconstructive periodontal surgery using various types of biomaterials
      to enhance periodontal wound healing/regeneration in human intrabony defects. In
      addition, the inherent problems associated with performing human histologic
      studies and in interpreting the results, as well as certain ethical
      considerations, are discussed. The results of the present systematic review
      indicate that periodontal regeneration in human intrabony defects can be achieved
      to a variable extent using a range of methods and materials. Periodontal
      regeneration has been observed following the use of a variety of bone grafts and
      substitutes, guided tissue regeneration, biological factors and combinations
      thereof. Combination approaches appear to provide the best outcomes, whilst
      implantation of alloplastic material alone demonstrated limited, to no,
      periodontal regeneration. 

PMID- 25867988
TI  - Periodontal and peri-implant wound healing following laser therapy.
AB  - Laser irradiation has numerous favorable characteristics, such as ablation or
      vaporization, hemostasis, biostimulation (photobiomodulation) and microbial
      inhibition and destruction, which induce various beneficial therapeutic effects
      and biological responses. Therefore, the use of lasers is considered effective
      and suitable for treating a variety of inflammatory and infectious oral
      conditions. The CO2 , neodymium-doped yttrium-aluminium-garnet (Nd:YAG) and diode
      lasers have mainly been used for periodontal soft-tissue management. With
      development of the erbium-doped yttrium-aluminium-garnet (Er:YAG) and erbium,
      chromium-doped yttrium-scandium-gallium-garnet (Er,Cr:YSGG) lasers, which can be
      applied not only on soft tissues but also on dental hard tissues, the application
      of lasers dramatically expanded from periodontal soft-tissue management to hard
      tissue treatment. Currently, various periodontal tissues (such as gingiva, tooth
      roots and bone tissue), as well as titanium implant surfaces, can be treated with
      lasers, and a variety of dental laser systems are being employed for the
      management of periodontal and peri-implant diseases. In periodontics, mechanical
      therapy has conventionally been the mainstream of treatment; however, complete
      bacterial eradication and/or optimal wound healing may not be necessarily
      achieved with conventional mechanical therapy alone. Consequently, in addition to
      chemotherapy consisting of antibiotics and anti-inflammatory agents, phototherapy
      using lasers and light-emitting diodes has been gradually integrated with
      mechanical therapy to enhance subsequent wound healing by achieving thorough
      debridement, decontamination and tissue stimulation. With increasing evidence of
      benefits, therapies with low- and high-level lasers play an important role in
      wound healing/tissue regeneration in the treatment of periodontal and peri
      implant diseases. This article discusses the outcomes of laser therapy in soft
      tissue management, periodontal nonsurgical and surgical treatment, osseous
      surgery and peri-implant treatment, focusing on postoperative wound healing of
      periodontal and peri-implant tissues, based on scientific evidence from currently
      available basic and clinical studies, as well as on case reports. 

PMID- 25867989
TI  - Influence of suturing on wound healing.
AB  - The present article describes the significance of suturing and appropriate suture
      materials in current periodontal and implant surgery. Synthetic, nonresorbable,
      monofilament threads appear to be advantageous. The physical and biological
      properties of such threads remain unchanged with use and, when used in small
      diameters (i.e. with lower breaking resistance), seem to promote passive wound
      closure. Wound healing at hard, nonshedding surfaces is conceptually a more
      complex process than is wound healing in most other sites of the oral cavity.
      Firm adaptation and stabilization of the flaps by optimal suturing ensures
      adhesion of the delicate fibrin clot to the nonshedding surface. The early
      formation and mechanical stability of the blood clot between the mucosal or
      mucoperiosteal flap and the wound bed are of paramount importance and hence
      suturing techniques must be considered as a key prerequisite to ensure optimal
      surgical outcomes. With the sophisticated surgical procedures now applied, there
      is a greater need for knowledge with regard to the various types of suturing
      techniques and materials available in order to achieve the above-mentioned goals.

PMID- 25867990
TI  - Clinical concepts for regenerative therapy in intrabony defects.
AB  - Evidence indicates that periodontal regeneration is an efficacious and
      predictable procedure for the treatment of isolated and multiple intrabony
      defects. Meta-analyses from systematic reviews indicate an added benefit, in
      terms of clinical attachment level gain, when demineralized freeze-dried bone
      allograft, barrier membranes and active biologic products/compounds are applied
      in addition to open flap debridement. On the other hand, a consistent amount of
      variability of the outcomes is evident among different studies and within the
      experimental population of each study. This variability is explained, at least in
      part, by different patient and defect characteristics. Patient-related factors
      include smoking habit, compliance with home oral hygiene and residual
      inflammation after cause-related therapy. Defect-associated factors include
      defect depth and radiographic angle, the number of residual bony walls, pocket
      depth and the degree of hypermobility. In addition, surgical-related variables,
      such as surgical skill, clinical experience and knowledge, and application of the
      different regenerative materials, have a significant impact on clinical outcomes.
      This paper presents a strategy to optimize the clinical outcomes of periodontal
      regeneration. The surgical design of the flap, the use of different regenerative
      materials and the application of appropriate passive sutures are discussed in
      this review along with the scientific foundations. 

PMID- 25867991
TI  - Clinical concepts for regenerative therapy in furcations.
AB  - Furcation involvements present one of the greatest challenges in periodontal
      therapy because furcation-involved molar teeth respond less favorably to
      conventional periodontal therapy compared with noninvolved molar or nonmolar
      teeth. Various regenerative procedures have been proposed and applied with the
      aim of eliminating the furcation defect or reducing the furcation depth. An
      abundance of studies and several systematic reviews have established the
      effectiveness of membrane therapy (guided tissue regeneration) for buccal Class
      II furcation involvement of mandibular and maxillary molars compared with open
      flap surgery. Bone grafts/substitutes may enhance the results of guided tissue
      regeneration. However, complete furcation closure is not a predictable outcome.
      Limited data and no meta-analyses are available on the effects of enamel matrix
      proteins for furcation regeneration. Enamel matrix protein therapy has
      demonstrated clinical improvements in the treatment of buccal Class II furcation
      defects in mandibular molars; however, complete closure of the furcation lesion
      is achieved only in a minority of cases. Neither guided tissue regeneration nor
      enamel matrix protein therapy have demonstrated predictable results for
      approximal Class II and for Class III furcations. Promising preclinical data from
      furcation regeneration studies in experimental animals is available for growth
      factor- and differentiation factor-based technologies, but very limited data are
      available from human clinical studies. Although cell-based therapies have
      received considerable attention in regenerative medicine, their experimental
      evaluation in the treatment of periodontal furcation lesions is at a very early
      stage of development. In summary, the indications and the limitations for
      currently available treatment modalities for furcation defects are well
      established. New regenerative treatments are clearly needed to improve the
      predictability of a complete resolution of furcation defects. 

PMID- 25867992
TI  - Periodontal plastic surgery.
AB  - The aim of the present article is to summarize current knowledge in terms of the
      etiology, diagnosis, prognosis and surgical treatment of gingival recession.
      Whilst the main etiological factors (i.e. toothbrushing trauma and bacterial
      plaque) are well established, challenges still remain to be solved in the
      diagnostic, prognostic and classification processes of gingival recession,
      especially when the main reference parameter - the cemento-enamel junction - is
      no longer detectable on the affected tooth or when there is a slight loss of
      periodontal interdental attachment. Root coverage in single type gingival
      recession defects is a very predictable outcome following the use of various
      surgical techniques. The coronally advanced flap, with or without connective
      tissue grafting, is the technique of choice. The adjunctive use of connective
      tissue grafts improves the probability of achieving complete root coverage.
      Surgical coverage of multiple gingival recessions is also predictable with the
      coronally advanced flap and the coronally advanced flap plus the connective
      tissue graft, but no data are available indicating which, and how many, gingival
      recessions should be treated adjunctively with connective tissue grafting in
      order to limit patient morbidity and improve the esthetic outcome. None of the
      allograft materials currently available can be considered as a full substitute
      for the connective tissue graft, even if some recent results are encouraging. The
      need for future studies with patient-based outcomes (i.e. esthetics and
      morbidity) as primary objectives is emphasized in this review. 

PMID- 25867993
TI  - Clinical approaches to treat peri-implant mucositis and peri-implantitis.
AB  - Therapies proposed for the treatment of peri-implant diseases are primarily based
      on the evidence available from treating periodontitis. The primary objective is
      elimination of the biofilm from the implant surface, and nonsurgical therapy is a
      commonly used treatment. A number of adjunctive therapies have been introduced to
      overcome accessibility problems or difficulties with decontamination of implant
      surfaces as a result of specific surface characteristics. It is now accepted that
      following successful decontamination, clinicians can attempt to regenerate the
      bone that was lost as a result of infection. The ultimate goal is re
      osseointegration, and a number of regenerative techniques have been introduced.
      By reviewing the existing evidence, it seems that peri-implant mucositis is
      reversible when appropriately treated. Additionally, a combined therapy
      (mechanical therapy with local antimicrobials as adjuncts) can serve as an
      alternative to surgical intervention when treating peri-implantits in cases not
      suitable for surgery. Surgical therapy is an effective method for treating peri
      implantitis, and various degrees of success of the use of regenerative procedures
      have been reported, regardless of whether or not radiographic evidence of defect
      fill has been achieved. Finally, no matter which therapy is employed, a
      prerequisite for the long-term stability of treatment results obtained is the
      ability of the patient to maintain good oral hygiene. 

PMID- 25867995
TI  - Object recognition memory deficit and depressive-like behavior caused by chronic
      ovariectomy can be transitorialy recovered by the acute activation of hippocampal
      estrogen receptors.
AB  - It is well known that estradiol (E2) replacement therapy is effective on
      restoring memory deficits and mood disorders that may occur during natural
      menopause or after surgical ovarian removal (ovariectomy, OVX). However, it is
      still unknown the effectiveness of acute and localized E2 administration on the
      effects of chronic OVX. Here we tested the hypothesis that the intra-hippocampal
      E2 infusion, as well as specific agonists of estrogen receptors (ERs) alpha
      (ERalpha) and beta (ERbeta), are able to mend novel object recognition (NOR)
      memory deficit and depressive-like behavior caused by 12 weeks of OVX. We found
      that both ERalpha and ERbeta activation, at earlier stages of consolidation,
      recovered the NOR memory deficit caused by 12 w of OVX. Conversely, only the
      ERbeta activation was effective in decreasing the depressive-like behavior caused
      by 12 w of OVX. Furthermore, we investigated the effect of OVX on hippocampal
      volume and ERs expression. The structural MRI showed no alteration in the
      hippocampus volume of 12 w OVX animals. Interestingly, ERalpha expression in the
      hippocampus decreased after one week of OVX, but increased in 12 w OVX animals.
      Overall, we may conclude that the chronic estrogen deprivation, induced by 12
      weeks of OVX, modulates the hippocampal ERalpha expression and induces NOR memory
      deficit and depressive-like behaviors. Nonetheless, it is noteworthy that the
      acute effects of E2 on NOR memory and depressive-like behavior are still apparent
      even after 12 weeks of OVX.

PMID- 25867994
TI  - An analysis of gene expression in PTSD implicates genes involved in the
      glucocorticoid receptor pathway and neural responses to stress.
AB  - We examined the association between posttraumatic stress disorder (PTSD) and gene
      expression using whole blood samples from a cohort of trauma-exposed white non
      Hispanic male veterans (115 cases and 28 controls). 10,264 probes of genes and
      gene transcripts were analyzed. We found 41 that were differentially expressed in
      PTSD cases versus controls (multiple-testing corrected p<0.05). The most
      significant was DSCAM, a neurological gene expressed widely in the developing
      brain and in the amygdala and hippocampus of the adult brain. We then examined
      the 41 differentially expressed genes in a meta-analysis using two replication
      cohorts and found significant associations with PTSD for 7 of the 41 (p<0.05),
      one of which (ATP6AP1L) survived multiple-testing correction. There was also
      broad evidence of overlap across the discovery and replication samples for the
      entire set of genes implicated in the discovery data based on the direction of
      effect and an enrichment of p<0.05 significant probes beyond what would be
      expected under the null. Finally, we found that the set of differentially
      expressed genes from the discovery sample was enriched for genes responsive to
      glucocorticoid signaling with most showing reduced expression in PTSD cases
      compared to controls. 

PMID- 25867996
TI  - Children's understanding of the costs and rewards underlying rational action.
AB  - Humans explain and predict other agents' behavior using mental state concepts,
      such as beliefs and desires. Computational and developmental evidence suggest
      that such inferences are enabled by a principle of rational action: the
      expectation that agents act efficiently, within situational constraints, to
      achieve their goals. Here we propose that the expectation of rational action is
      instantiated by a naive utility calculus sensitive to both agent-constant and
      agent-specific aspects of costs and rewards associated with actions. In four
      experiments, we show that, given an agent's choices, children (range: 5-6 year
      olds; N=96) can infer unobservable aspects of costs (differences in agents'
      competence) from information about subjective differences in rewards (differences
      in agents' preferences) and vice versa. Moreover, children can design informative
      experiments on both objects and agents to infer unobservable constraints on
      agents' actions.

PMID- 25867997
TI  - Constituents of political cognition: Race, party politics, and the alliance
      detection system.
AB  - Research suggests that the mind contains a set of adaptations for detecting
      alliances: an alliance detection system, which monitors for, encodes, and stores
      alliance information and then modifies the activation of stored alliance
      categories according to how likely they will predict behavior within a particular
      social interaction. Previous studies have established the activation of this
      system when exposed to explicit competition or cooperation between individuals.
      In the current studies we examine if shared political opinions produce these same
      effects. In particular, (1) if participants will spontaneously categorize
      individuals according to the parties they support, even when explicit cooperation
      and antagonism are absent, and (2) if party support is sufficiently powerful to
      decrease participants' categorization by an orthogonal but typically-diagnostic
      alliance cue (in this case the target's race). Evidence was found for both:
      Participants spontaneously and implicitly kept track of who supported which
      party, and when party cross-cut race-such that the race of targets was not
      predictive of party support-categorization by race was dramatically reduced. To
      verify that these results reflected the operation of a cognitive system for
      modifying the activation of alliance categories, and not just socially-relevant
      categories in general, an identical set of studies was also conducted with in
      which party was either crossed with sex or age (neither of which is predicted to
      be primarily an alliance category). As predicted, categorization by party
      occurred to the same degree, and there was no reduction in either categorization
      by sex or by age. All effects were replicated across two sets of between-subjects
      conditions. These studies provide the first direct empirical evidence that party
      politics engages the mind's systems for detecting alliances and establish two
      important social categorization phenomena: (1) that categorization by age is,
      like sex, not affected by alliance information and (2) that political contexts
      can reduce the degree to which individuals are represented in terms of their
      race. 

PMID- 25867998
TI  - Selective memory retrieval in social groups: When silence is golden and when it
      is not.
AB  - Previous research has shown that the selective remembering of a speaker and the
      resulting silences can cause forgetting of related, but unmentioned information
      by a listener (Cuc, Koppel, & Hirst, 2007). Guided by more recent work that
      demonstrated both detrimental and beneficial effects of selective memory
      retrieval in individuals, the present research explored the effects of selective
      remembering in social groups when access to the encoding context at retrieval was
      maintained or impaired. In each of three experiments, selective retrieval by the
      speaker impaired recall of the listener when access to the encoding context was
      maintained, but it improved recall of the listener when context access was
      impaired. The results suggest the existence of two faces of selective memory
      retrieval in social groups, with a detrimental face when the encoding context is
      still active at retrieval and a beneficial face when it is not. The role of
      silence in social recall thus seems to be more complex than was indicated in
      prior work, and mnemonic silences on the part of a speaker can be "golden" for
      the memories of a listener under some circumstances, but not be "golden" under
      others. 

PMID- 25867999
TI  - The role of sphingolipids in endothelial barrier function.
AB  - Sphingolipids are a ubiquitous family of essential lipids with an increasingly
      understood role as biologically active mediators in numerous physiologic and
      pathologic processes. Two particular sphingolipid species, sphingosine-1
      phosphate and ceramide, and their metabolites interact both directly and
      indirectly with endothelial cells to regulate vascular permeability. Sphingosine
      1-phosphate generally augments endothelial integrity while ceramide tends to
      promote vascular leak, and a tight balance between the two is necessary to
      maintain normal physiologic function. The mechanisms by which sphingolipids
      regulate endothelial barrier function are complex and occur through multiple
      different pathways, and disruptions or imbalances in these pathways have been
      implicated in a number of specific disease processes. With improved understanding
      of sphingolipid biology, endothelial function, and the interactions between the
      two, several targets for therapeutic intervention have emerged and there is
      immense potential for further advancement in this field. 

PMID- 25868000
TI  - The volume-regulated anion channel is formed by LRRC8 heteromers - molecular
      identification and roles in membrane transport and physiology.
AB  - Cellular volume regulation is fundamental for numerous physiological processes.
      The volume-regulated anion channel, VRAC, plays a crucial role in regulatory
      volume decrease. This channel, which is ubiquitously expressed in vertebrates,
      has been vastly characterized by electrophysiological means. It opens upon cell
      swelling and conducts chloride and arguably organic osmolytes. VRAC has been
      proposed to be critically involved in various cellular and organismal functions,
      including cell proliferation and migration, apoptosis, transepithelial transport,
      swelling-induced exocytosis and intercellular communication. It may also play a
      role in pathological states like cancer and ischemia. Despite many efforts, the
      molecular identity of VRAC had remained elusive for decades, until the recent
      discovery of heteromers of LRRC8A with other LRRC8 family members as an essential
      VRAC component. This identification marks a starting point for studies on the
      structure-function relation, for molecular biological investigations of its cell
      biology and for re-evaluating the physiological roles of VRAC. This review
      recapitulates the identification of LRRC8 heteromers as VRAC components, depicts
      the similarities between LRRC8 proteins and pannexins, and discussed whether VRAC
      conducts larger osmolytes. Furthermore, proposed physiological functions of VRAC
      and the present knowledge about the physiological significance of LRRC8 proteins
      are summarized and collated. 

PMID- 25868001
TI  - In-vitro anthelmintic activity of three Bangladeshi plants against Paramphistomum
      cervi and Haemonchus contortus.
AB  - BACKGROUND: Conventional plant-based therapies act as an important therapeutic
      tool for the treatment of worm infections all over the world and continuous
      evaluation of medicinal plants to find new potential lead compounds should be
      carried out. METHODS: In-vitro analysis was conducted to evaluate the probable
      anthelmintic effect of crude aqueous and hydroalcoholic extracts of Ananas
      sativus leaves, Erythrina variegata barks and Alocasia indica rootstocks, against
      adult Paramphistomum cervi (Trematoda) and Haemonchus contortus (Nematode).
      RESULTS: Among all three concentrations (25, 50, and 100 mg/mL), the
      hydroalcoholic leaf extract of A. sativus exhibited paralysis and death time
      ranged between 7.26 to 26.76 min and 15.40 to 35.55 min respectively for P. cervi
      while that for H. contortus was 14.70 to 42.43 min and 23.43 to 56.34 min,
      respectively. Moreover, aqueous extract exhibited paralysis and death time ranged
      between 7.66 to 28.72 min and 18.30 to 33.00 min, respectively, for P. cervi
      whereas paralysis and death time ranged between 23.34 to 37.88 min and 31.08 to
      58.30 min respectively for H. contortus. Both extracts of E. variegata bark and
      A. indica tuber showed comparatively less significant anthelmintic activity. All
      results were statistically significant (p < 0.001). CONCLUSIONS: A. sativus leaf
      displayed favorable anthelmintic activity on both P. cervi and H. contortus,
      whereas E. variegata barks and A. indica rootstocks showed insignificant result.

PMID- 25868002
TI  - Uncinate fasciculus connectivity in patients with psychogenic nonepileptic
      seizures: A preliminary diffusion tensor tractography study.
AB  - The amygdala, hippocampus, and medial prefrontal cortex are limbic brain regions
      connected by the uncinate fasciculus (UF) and implicated in emotion regulation.
      The aim of this study was to assess the connectivity characteristics of the UF in
      patients with psychogenic nonepileptic seizures (PNES) and matched healthy
      controls. We hypothesized that white matter connectivity of the UF in patients
      with PNES would differ from that in healthy controls. Eight patients with PNES
      and eight age- and sex-matched healthy controls underwent 3T MRI and 32-direction
      diffusion tensor imaging (DTI). Computation of DTI indices including fractional
      anisotropy (FA) and diffusion tensor tractography was performed. Two regions of
      interest were defined to manually trace the UF in each hemisphere for each
      subject. Fractional anisotropy and the number of reconstructed streamlines for
      the left and right hemispheres of the UF and the degree of asymmetry for each
      measure were compared between groups. Correlations between UF measures and
      clinical variables were also performed. Patients with PNES exhibited a
      significantly greater number of UF streamlines in the right hemisphere tract than
      in the left hemisphere (p=0.031), with such difference not observed in controls
      (p=0.81). This was reflected in a significant group difference in the asymmetry
      index (AI) for the number of streamlines, with more rightward asymmetry in
      patients with PNES (p=0.021). Average FA of the UF was similar between groups and
      between hemispheres for each group (all p>0.05). Age at illness onset was
      correlated with the AI for FA (r=-0.87; p=0.0045). Previously observed
      differences in emotion processing between controls and patients with PNES may be
      related to the differences in the rightward asymmetry in the number of UF
      streamlines in patients with PNES. Age at PNES onset appears to also have a role
      in the FA asymmetry of the UF. This is the first study to investigate the
      structural connectivity in these regions involved in emotional regulation in
      patients with PNES; further research is necessary to clarify the complex
      relationships between clinical measures and DTI characteristics. 

PMID- 25868004
TI  - Pressure-dependent kinetics of initial reactions in iso-octane pyrolysis.
AB  - This study focuses on the studies of the main pressure-dependent reaction types
      of iso-octane (iso-C8H18) pyrolysis, including initial C-C bond fission of iso
      octane, isomerization, and beta-scission reactions of the alkyl radicals produced
      by the C-C bond fission of iso-octane. For the C-C bond fission of iso-octane,
      the minimum energy potentials are calculated at the CASPT2(2e,2o)/6
      31+G(d,p)//CAS(2e,2o)/6-31+G(d,p) level of theory. For the isomerization and the
      beta-scission reactions of the alkyl radicals, the optimization of the geometries
      and the vibrational frequencies of the reactants, transition states, and products
      are performed at the B3LYP/CBSB7 level, and their single point energies are
      calculated by using the composite CBS-QB3 method. Variable reaction coordinate
      transition state theory (VRC-TST) is used for the high-pressure limit rate
      constant calculation and Rice-Ramsperger-Kassel-Marcus/master equation (RRKM/ME)
      is used to calculate the pressure-dependent rate constants of these channels with
      pressure varying from 0.01-100 atm. The rate constants obtained in this work are
      in good agreement with those available from literatures. We have updated the rate
      constants and thermodynamic parameters for species involved in these reactions
      into a current chemical kinetic mechanism and also have improved the
      concentration profiles of main products such as C3H6 and C4H6 in the shock tube
      pyrolysis of iso-octane. The results of this study provide insight into the
      pyrolysis of iso-octane and will be helpful in the future development of branched
      paraffin kinetic mechanisms. 

PMID- 25868003
TI  - Community perceptions of developmental and behavioral problems experienced by
      children living with epilepsy on the Kenyan coast: A qualitative study.
AB  - Childhood epilepsy is common in Africa. However, there are little data on the
      developmental and behavioral problems experienced by children living with
      epilepsy, especially qualitative data that capture community perceptions of the
      challenges faced by these children. Identifying these perceptions using
      qualitative approaches is important not only to help design appropriate
      interventions but also to help adapt behavioral tools that are culturally
      appropriate. We documented the description of these problems as perceived by
      parents and teachers of children with or without epilepsy. The study involved 70
      participants. Data were collected using in-depth interviews and focus group
      discussions and were analyzed using NVIVO to identify major themes. Our analysis
      identified four major areas that are perceived to be adversely affected among
      children with epilepsy. These included internalizing and externalizing problems
      such as aggression, temper tantrums, and excessive crying. Additionally,
      developmental delay, especially cognitive deficits and academic underachievement,
      was also identified as a major problematic area. There is a need to supplement
      these findings with quantitative estimates and to develop psychosocial and
      educational interventions to rehabilitate children with epilepsy who have these
      difficulties. 

PMID- 25868005
TI  - Rational Topological Design for Fluorescence Enhancement upon Aggregation of
      Distyrylfuran Derivatives.
AB  - A series of 2,5-distyrylfuran derivatives bearing pentafluorophenyl- and
      cyanovinyl units have been synthesized for aggregation-induced emission (AIE).
      The effect of the type and extent of the supramolecular connections on the AIE of
      the furan derivatives were examined and correlated with their X-ray crystal
      structures. It was found that the simultaneous presence of cyano and
      perfluorophenyl units strongly enhances the fluorescence upon aggregation. Single
      crystal X-ray diffraction analysis confirmed that C?H???F, F???F, C?H???nitrile,
      Ar???ArF (Ar=aryl, ArF =fluoroaryl), and nitrile???ArF intra- and intermolecular
      interactions drive the topology of the molecule and that solid-state
      supramolecular contacts favor AIE of the furan derivatives. 

PMID- 25868006
TI  - Tendon rupture associated with excessive smartphone gaming.
AB  - IMPORTANCE: Excessive use of smartphones has been associated with injuries.
      OBSERVATIONS: A 29-year-old, right hand-dominant man presented with chronic left
      thumb pain and loss of active motion from playing a Match-3 puzzle video game on
      his smartphone all day for 6 to 8 weeks. On physical examination, the left
      extensor pollicis longus tendon was not palpable, and no tendon motion was noted
      with wrist tenodesis. The thumb metacarpophalangeal range of motion was 10
      degrees  to 80 degrees , and thumb interphalangeal range of motion was 30 degrees
      to 70 degrees . The clinical diagnosis was rupture of the left extensor pollicis
      longus tendon. The patient subsequently underwent an extensor indicis proprius (1
      of 2 tendons that extend the index finger) to extensor pollicis longus tendon
      transfer. During surgery, rupture of the extensor pollicis longus tendon was seen
      between the metacarpophalangeal and wrist joints. CONCLUSIONS AND RELEVANCE: The
      potential for video games to reduce pain perception raises clinical and social
      considerations about excessive use, abuse, and addiction. Future research should
      consider whether pain reduction is a reason some individuals play video games
      excessively, manifest addiction, or sustain injuries associated with video
      gaming.

PMID- 25868007
TI  - Women in very low quality marriages gain life satisfaction following divorce.
AB  - Although marital dissolution is associated with increased risk for poor mental
      and physical health outcomes, many people report improvements in functioning
      after divorce. To study the hypothesis that women in lower quality marriages
      would report the best outcomes upon separation/divorce, we investigated the
      combined effects of marital quality, gender, and marital status for predicting
      changes in life satisfaction (LS). Participants (N = 1,639; 50.3% men) were drawn
      from a nationally representative sample (Midlife in the United States Study),
      which included assessments of marital quality, marital status, and LS, at 2 time
      points (T1 and T2), roughly 10 years apart. Hierarchical linear regression
      analyses revealed an interaction between marital quality, marital status, and
      gender when predicting residual change in LS. Divorced women evidenced a negative
      association between marital quality and later LS, whereas continuously married
      women had a positive association between marital quality and later LS. In
      addition, women in higher quality marriages that become divorced showed the
      lowest LS, and women in lowest quality marriages show the highest LS among women
      with similar levels of marital quality. There was no association between marital
      quality and later LS for divorced or continuously married men. This work extends
      prior findings regarding gender differences in marital quality to postdivorce
      well-being, and suggests women in the lowest quality marriages may gain LS
      following divorce.

PMID- 25868008
TI  - Patterns and predictors of coparenting after unmarried parents part.
AB  - Nonmarital childbearing has increased dramatically during the past several
      decades, and the majority of unmarried couples will break up while their child is
      still young. As a result, many children will be raised by their biological
      parents living apart, ideally working together as effective coparents. In this
      article, we use data from the Fragile Families and Child Wellbeing Study (N =
      1,193) to describe the trajectories of coparenting over 6 years following the end
      of a nonmarital relationship and to identify individual and interpersonal
      characteristics associated with better coparenting over time. Results from growth
      mixture models (GMMs) suggest that there are 4 primary trajectories of
      coparenting over time, and results from multinomial logit models show that
      couples' race/ethnicity, maternal health, and parents' relationship and fertility
      characteristics are the most salient predictors of coparenting trajectories.
      These results highlight the heterogeneity of parents' interaction vis-a-vis their
      common child after a nonmarital union dissolves and point to the challenges of
      supporting families and children amid high instability.

PMID- 25868009
TI  - Near infrared (NIr) light increases expression of a marker of mitochondrial
      function in the mouse vestibular sensory epithelium.
AB  - Strategies for attenuating decline in balance function with increasing age are
      predominantly focused on physical therapies including balance tasks and exercise.
      However, these approaches do not address the underlying causes of balance
      decline. Using mice, the impact of near infrared light (NIr) on the metabolism of
      cells in the vestibular sensory epithelium was assessed. Data collected shows
      that this simple and safe intervention may protect these vulnerable cells from
      the deleterious effects of natural aging. mRNA was extracted from the isolated
      peripheral vestibular sensory epithelium (crista ampullaris and utricular macula)
      and subsequently transcribed into a cDNA library. This library was then probed
      for the expression of ubiquitous antioxidant (SOD-1). Antioxidant gene expression
      was then used to quantify cellular metabolism. Using transcranial delivery of NIr
      in young (4 weeks) and older (8-9 months) mice, and a brief treatment regime (90
      sec/day for 5 days), this work suggests NIr alone may be sufficient to improve
      mitochondrial function in the vestibular sensory epithelium. Since there are
      currently no available, affordable, non-invasive methods of therapy to improve
      vestibular hair cell function, the application of external NIr radiation provides
      a potential strategy to counteract the impact of aging on cellular metabolism
      inthe vestibular sensory epithelium.

PMID- 25868010
TI  - Natural organic matter-induced alleviation of the phytotoxicity to rice (Oryza
      sativa L.) caused by copper oxide nanoparticles.
AB  - Natural organic matter (NOM) can interact with engineered nanoparticles (NPs) in
      the environment and modify their behavior and toxicity to organisms. In the
      present study, the phytotoxicity of copper oxide (CuO) NPs to rice seedlings in
      the presence of humic acid as a model NOM was investigated. The results showed
      that CuO NPs induced the inhibition of root elongation, aberrations in root
      morphology and ultrastructure, and losses of cell viability and membrane
      integrity. The adverse effects partly resulted from the generation of reactive
      oxygen species caused by CuO NPs, which led to lipid peroxidation, mitochondrial
      dysfunction, and programmed cell death in rice seedlings. However, all the
      phytotoxicity was alleviated with the addition of humic acid because humic acid
      coatings on nanoparticle surfaces enhanced electrostatic and steric repulsion
      between the CuO NPs and the plant cell wall/membrane, reducing contact between
      NPs and plant and CuO NP-induced oxidative damage to plant cells. The present
      study's results shed light on the mechanism underlying NP phytotoxicity and
      highlight the influence of NOM on the bioavailability and toxicity of NPs.

PMID- 25868011
TI  - Single-stage dynamic reanimation of the smile in irreversible facial paralysis by
      free functional muscle transfer.
AB  - Unilateral facial paralysis is a common disease that is associated with
      significant functional, aesthetic and psychological issues. Though idiopathic
      facial paralysis (Bell's palsy) is the most common diagnosis, patients can also
      present with a history of physical trauma, infectious disease, tumor, or
      iatrogenic facial paralysis. Early repair within one year of injury can be
      achieved by direct nerve repair, cross-face nerve grafting or regional nerve
      transfer. It is due to muscle atrophy that in long lasting facial paralysis
      complex reconstructive methods have to be applied. Instead of one single
      procedure, different surgical approaches have to be considered to alleviate the
      various components of the paralysis. The reconstruction of a spontaneous dynamic
      smile with a symmetric resting tone is a crucial factor to overcome the
      functional deficits and the social handicap that are associated with facial
      paralysis. Although numerous surgical techniques have been described, a two-stage
      approach with an initial cross-facial nerve grafting followed by a free
      functional muscle transfer is most frequently applied. In selected patients
      however, a single-stage reconstruction using the motor nerve to the masseter as
      donor nerve is superior to a two-stage repair. The gracilis muscle is most
      commonly used for reconstruction, as it presents with a constant anatomy, a
      simple dissection and minimal donor site morbidity. Here we demonstrate the pre
      operative work-up, the post-operative management, and precisely describe the
      surgical procedure of single-stage microsurgical reconstruction of the smile by
      free functional gracilis muscle transfer in a step by step protocol. We further
      illustrate common pitfalls and provide useful tips which should enable the reader
      to truly comprehend the procedure. We further discuss indications and limitations
      of the technique and demonstrate representative results. 

PMID- 25868012
TI  - Family health history: the case for better tools.

PMID- 25868013
TI  - Expanding the evidence base supporting shorter treatment durations for multidrug
      resistant tuberculosis.

PMID- 25868014
TI  - Are pulmonary non-tuberculous mycobacteria of concern in the Western Pacific
      Region?

PMID- 25868015
TI  - World Asthma Day, 5 May 2015.

PMID- 25868016
TI  - The Industrial Revolution and the decline in death rates from tuberculosis.

PMID- 25868017
TI  - Advances in the diagnosis of tuberculosis: current status and future prospects.
AB  - Lack of diagnosis and diagnostic capacity remain barriers to tuberculosis (TB)
      control. This review describes recent advances in TB diagnostics, the current TB
      diagnostic landscape, and some of the key challenges in the quest for accurate,
      simple diagnostic tests that have meaningful impact on the health of individual
      patients and on TB epidemiology. 

PMID- 25868018
TI  - High effectiveness of a 12-month regimen for MDR-TB patients in Cameroon.
AB  - SETTING: Two specialised multidrug-resistant tuberculosis (MDR-TB) treatment
      units in Cameroon. OBJECTIVE: To assess outcome and adverse drug events with a
      standardised 12-month regimen for MDR-TB among second-line drug naive patients.
      DESIGN: Prospective observational study of MDR-TB patients treated with a
      standardised 12-month regimen including gatifloxacin, clofazimine, prothionamide,
      ethambutol and pyrazinamide throughout, supplemented by kanamycin and isoniazid
      during an intensive phase of a minimum of 4 months. Progress was monitored
      monthly until treatment completion and twice over one year after treatment
      cessation. RESULTS: Eighty-seven potentially eligible patients were lost and
      never treated due to delayed availability of test results. Among the 150/236
      eligible and treated patients, 134 (89%) successfully completed treatment, 10
      died, 5 were lost, 1 failed and none relapsed. The patients' mean age was 33.7
      years (range 17-68), 73 (49%) were females, 120 (80%) had failed on previous
      treatment, 30 (20%) were human immunodeficiency virus seropositive, 62 (43%) had
      a body mass index <18.5 kg/m(2) and 41 (27%) had radiographic involvement of five
      or six of the six lung zones. The most important adverse drug event was hearing
      impairment, which occurred in 46 of 106 (43%) patients. CONCLUSIONS: These
      results add further evidence for the usefulness of shorter, standardised regimens
      among patients without second-line drug resistance.

PMID- 25868019
TI  - Changes in treatment outcomes of multidrug-resistant tuberculosis.
AB  - SETTING: After several changes in treatment modalities, it is time to re-evaluate
      treatment outcomes of multidrug-resistant tuberculosis (MDR-TB). OBJECTIVE: To
      evaluate treatment outcomes, elucidate changes in outcomes over time and identify
      predictors of treatment success for MDR-TB. DESIGN: Patients diagnosed with MDR
      TB at a tertiary referral centre in South Korea between January 2006 and December
      2010 were included. Treatment modalities and outcomes were assessed. Predictors
      of treatment success were analysed using multiple logistic regression. The
      treatment modalities and outcomes of these patients were compared with those of
      MDR-TB patients between January 1996 and December 2005. RESULTS: Of the 123 MDR
      TB patients diagnosed during the later study period, treatment was successful in
      103 (83.7%). Extensive drug resistance (OR 0.31, P = 0.044) and additional
      resistance to fluoroquinolones (OR 0.23, P = 0.039) were inversely associated
      with treatment success. The treatment success rate improved from 53.5% in 1996
      2000 to 68.8% in 2001-2005 and 83.7% in 2006-2010 (P < 0.001). Improved outcomes
      were accompanied with more frequent use of later-generation fluoroquinolones and
      linezolid and less frequent surgical resection. CONCLUSION: Treatment outcomes
      for MDR-TB improved at a tertiary referral centre in South Korea. The improvement
      was associated with more frequent use of later-generation fluoroquinolones and
      linezolid.

PMID- 25868020
TI  - Multidrug-resistant tuberculosis in the Amazonas State, Brazil, 2000-2011.
AB  - SETTINGS: Amazonas is facing increasing challenges in tuberculosis (TB) control,
      with nearly 3000 cases per year, and multidrug-resistant TB (MDR-TB) may
      jeopardise the TB control programme. OBJECTIVE: To assess the number of MDR-TB
      cases in the Amazonas and to improve estimates of the burden of TB. DESIGNS: The
      Brazilian National Mandatory Disease Reporting System (SINAN) and the Brazilian
      Epidemiological Surveillance System of Multidrug Resistance (TBMR) were searched
      for MDR-TB cases in the State of Amazonas from 2000 to 2011. RESULTS: Eighty-one
      MDR-TB cases were notified. The rates of primary MDR-TB, initial MDR-TB during
      the first treatment regimen and acquired MDR-TB were respectively 3.8%, 13.7% and
      82.7%; 26.9% of previously treated patients had ? 4 treatment cycles. The MDR-TB
      cases reported 263 contacts, only 35.0% of whom were examined. The cure and death
      rates among the 81 patients with MDR-TB were respectively 45.7% and 25.9%.
      CONCLUSIONS: The number of MDR-TB cases seems incompatible with the high TB
      prevalence in the Amazonas. Most patients were unaware of contact with TB
      patients. TB is endemic in the Amazonas. This highlights the need for improving
      resistance investigation among all TB cases.

PMID- 25868021
TI  - The impact of sputum quality on tuberculosis diagnosis: a systematic review.
AB  - OBJECTIVE: To perform a systematic review to evaluate the impact of sputum
      quality on the yield of tuberculosis (TB) diagnostic tests. METHODS: We searched
      PubMed, EMBASE, LILACS and the Cochrane Database to identify studies that
      addressed 1) the impact of sputum quality on the proportion of sputum samples
      with Mycobacterium tuberculosis detected using smear, culture or polymerase chain
      reaction (PCR); and 2) the impact of pre-sputum collection interventions on
      sputum quality and M. tuberculosis detection. RESULTS: Ten studies met the
      eligibility criteria for review inclusion. Five studies assessed macroscopic
      and/or microscopic sputum quality characteristics and M. tuberculosis detection.
      The other five studies assessed the impact of pre-sputum collection interventions
      on sputum quality and M. tuberculosis detection. No studies assessed the impact
      of sputum quality on PCR-based diagnostic tests. CONCLUSION: Definitive
      conclusions about the utility of sputum quality assessments are limited by the
      paucity of, and heterogeneity within, the available data. Given the potential for
      sputum quality assessments to enhance diagnostic yield and prevent wasteful
      laboratory testing, further research into this field is urgently needed.

PMID- 25868023
TI  - Molecular detection of Mycobacterium tuberculosis from sputum transported in
      PrimeStore((r)) from rural settings.
AB  - SETTING: Mopani District, South Africa. OBJECTIVE: To explore remote, molecular
      detection of Mycobacterium tuberculosis from sputum transported using
      PrimeStore((r)) Molecular Transport Medium (PS-MTM) compared to settings where
      microscopy or Xpert((r)) MTB/RIF is used as the baseline test. DESIGN: Two sputum
      specimens were collected from patients with cough of ? 2 weeks at clinics in
      rural South Africa. Shortly after expectoration and before processing using
      Xpert, microscopy and liquid culture, a flocked swab was swirled in each of these
      specimens and placed in PS-MTM. Swabs were stored and transported to the United
      States at ambient temperature for real-time PrimeMix((r)) polymerase chain
      reaction (PM-PCR). RESULTS: Of 132 patients, 23 (17%) were positive on
      microscopy, 39 (30%) on Xpert and 44 (33%) by PS-MTM/PM-PCR. Concordance of PS
      MTM/PM-PCR with positive microscopy and Xpert was respectively 96% and 85%. Of
      107 microscopy-negative samples, 22 (21%) were positive using PS-MTM/PM-PCR,
      while 11/91 (12%) Xpert-negative samples were PS-MTM/PM-PCR-positive. PS-MTM/PM
      PCR positivity was significantly higher than smear microscopy positivity (P <
      0.001), but similar to Xpert (P = 0.33). CONCLUSION: PCR testing of specimens
      transported in PS-MTM would enhance TB diagnosis in settings where smear
      microscopy is the baseline diagnostic test, and could provide an alternative in
      settings where Xpert testing is not available.

PMID- 25868022
TI  - Introducing new tuberculosis diagnostics: the impact of Xpert((r)) MTB/RIF
      testing on case notifications in Nepal.
AB  - SETTING: The Xpert((r)) MTB/RIF assay is a highly sensitive molecular test with
      the potential to improve tuberculosis (TB) case detection. However, evidence
      supporting this potential at a programme level is minimal. METHODS: Xpert testing
      following smear microscopy and chest X-ray was implemented as part of routine
      case finding in 16 districts of Eastern Nepal. Changes in TB case notification
      were evaluated based on a pre/post analysis, as were expected notifications based
      on linear trend. RESULTS: A total of 9723 Xpert tests were performed, resulting
      in the identification of 1662 Mycobacterium tuberculosis-positive patients.
      Despite a previous declining trend in notifications, annual bacteriologically
      positive TB notifications increased by 15.2% during the intervention, from 3390
      to 3906. However, annual notifications of pulmonary TB dropped by 8.5% overall,
      from 5123 to 4688. Both observations were significantly different from expected
      notifications based on historical trends. Treatment initiation for drug-resistant
      TB almost doubled. DISCUSSION: Xpert testing significantly increased
      bacteriologically positive TB notifications, but large reductions in empiric
      treatment of smear-negative disease reduced the number of pulmonary TB
      notifications overall. While better diagnostics remain critical, focusing solely
      on superior test sensitivity may not increase TB case notifications. Additional
      interventions are required to reach the millions of people with TB who are missed
      by routine services.

PMID- 25868024
TI  - Intra-gastric string test: an effective tool for diagnosing tuberculosis in
      adults unable to produce sputum.
AB  - SETTING: Tuberculosis (TB) diagnosis is challenging in patients who are unable to
      produce sputum. The string test, a method for retrieving enteropathogens, is a
      potential alternative diagnostic tool. OBJECTIVES: To compare the TB detection
      yield and tolerability of the string test and that of sputum induction in adults
      with presumed TB in Uganda. DESIGN: Cross-sectional study. String test and sputum
      induction were performed consecutively in patients unable to produce sputum. The
      string was removed after a 2-h intra-gastric downtime. Sputum induction used
      nebulised 5% saline for 20 min. Light-emitting diode fluorescence microscopy,
      Lowenstein-Jensen and MGIT culture were performed on all specimens, and the
      Xpert((r)) MTB/RIF assay on a subset. Tolerability questionnaires were
      administered. RESULTS: Of 210 patients included in the study, 59% were human
      immunodeficiency virus (HIV) positive and 50 (23.8%) were diagnosed with TB. Of
      these, 48 (96.0%) were detected with the string test and 46 (92.0%) with sputum
      induction. In patients with specimens collected using both methods for paired
      analysis, the yield of microscopy detection with the string test was 13.8%
      (26/188) vs. 13.3% (25/188) with sputum induction (P = 1.0). The yield increased
      to 22.9% (42/183) using culture for string test vs. 24.6% (45/183) for sputum
      induction (P = 0.37). Xpert detected TB in 15/96 (15.6%) patients with the string
      test vs. 17/96 (17.7%) with sputum induction (P = 0.62). Tolerability was
      comparable. CONCLUSION: The string test was well tolerated and provided similar
      yields to sputum induction, offering a viable alternative in resource-limited
      settings with minimal risk of transmission.

PMID- 25868025
TI  - Evaluation of latent tuberculous infection and treatment completion for refugees
      in Philadelphia, PA, 2010-2012.
AB  - SETTING: Philadelphia, PA, USA. OBJECTIVES: To compare the evaluation and
      treatment of latent tuberculous infection (LTBI) in refugees seen at member
      clinics of the Philadelphia Refugee Health Collaborative (PRHC) vs. non-PRHC
      clinics. DESIGN: Refugees with Class B (non-communicable) tuberculosis (TB)
      admitted to the United States from 2010 to 2012 who were being treated at PRHC
      clinics were compared to those treated at non-PRHC clinics. Odds ratios (ORs) for
      attending a follow-up appointment, completing treatment, and time from arrival to
      the United States to the first TB screening test were calculated. RESULTS: Of the
      2094 refugees who arrived in Philadelphia in 2010-2012, the Philadelphia
      Department of Public Health was notified of 149 who required additional
      evaluation for TB. Among these, 57 (38.3%) were confirmed to have LTBI, and none
      were diagnosed with active TB. All LTBI cases were recommended for anti
      tuberculosis prophylaxis and 43 (75.4%) completed treatment. Refugees receiving
      care from PRHC clinics were more likely to be screened within 30 days of arrival
      (OR 4.70, 95%CI 2.12-10.44), attend a follow-up appointment (OR 4.53, 95%CI 1.36
      16.27), and complete treatment (OR 9.44, 95%CI 2.39-37.3). CONCLUSION: Refugees
      who attended PRHC clinics were more likely to be evaluated promptly and to
      complete LTBI treatment. The PRHC clinics serve as a model for communities
      seeking to improve refugee health care.

PMID- 25868026
TI  - Analysis of risk factors for tuberculous infection following exposure at a
      homeless shelter.
AB  - SETTING: A homeless shelter for men aged ? 50 years in Seattle, Washington, USA.
      OBJECTIVES: We examined risk factors for tuberculous infection following exposure
      to an active pulmonary tuberculosis (TB) case residing in a homeless shelter
      setting. METHODS: A contact investigation identified shelter clients exposed to
      the index case; these contacts were then assessed for tuberculous infection. Risk
      factors, including proximity and duration of exposure to the index case, were
      evaluated for association with infection. A retrospective cohort study was
      conducted and a multivariate logistic regression model determined the magnitude
      of the association between tuberculous infection and significant risk factors.
      RESULTS: Of the 64 contacts evaluated, 25 (39%) had latent tuberculous infection
      and one had active TB. The multivariate logistic regression model found that
      duration of exposure and birthplace were significantly associated with odds of
      infection. CONCLUSIONS: Birthplace and duration of exposure were significant risk
      factors for tuberculous infection, underscoring the importance of this
      information when prioritizing contact investigations after TB exposure in
      congregate settings. We recommend that public health agencies work with homeless
      shelters to ensure that clients' attendance records contain the necessary
      information to facilitate contact tracing during public health TB investigations.

PMID- 25868027
TI  - Role of confirmatory interferon-gamma release assays in school outbreaks of
      tuberculosis in South Korea.
AB  - OBJECTIVE: To investigate the usefulness of confirmatory QuantiFERON((r)) (QFT)
      testing among tuberculin skin test (TST) positive contacts to diagnose latent
      tuberculous infection (LTBI) in tuberculosis (TB) outbreaks among adolescents.
      DESIGN: We used the Korean national claims database to identify the development
      of active TB disease in relation to initial TST (cut-off 10 mm induration) and
      subsequent QFT results. RESULTS: A total of 7475 contacts in 89 schools were
      divided into four groups: TST- (n = 5714), TST+/QFT+ (n = 534), TST+/QFT- (n =
      697) and TST+ only (n = 530). The mean duration of follow-up was 3.9 +/- 0.9
      years. For contacts with no LTBI treatment (n = 6868), TB incidence rates per
      1000 person-years (py) and the adjusted hazard ratio (HR) compared with TST-
      individuals were as follows: TST+/QFT+, 66.2/1000 py (HR 35.59, 95%CI 14.03
      90.31, P < 0.001); TST+ only, 10.1/1000 py (HR 5.16, 95%CI 2.91-9.17, P < 0.001);
      TST+/QFT-, 4.0/1000 py (HR 2.05, 95%CI 1.05-4.01, P = 0.035); and TST- 2.0/1000
      py. The TB progression rate was significantly higher in TST+/QFT+ than in
      TST+/QFT- individuals (HR 16.82, 95 CI 5.84-48.46, P < 0.001). CONCLUSION: A
      confirmatory QFT for TST+ contacts could reduce the number of candidates for LTBI
      treatment after school TB outbreaks.

PMID- 25868029
TI  - Changes in lung function according to disease extent before and after pulmonary
      tuberculosis.
AB  - OBJECTIVE: To evaluate changes in lung function in individuals before and after
      treatment for pulmonary tuberculosis (PTB) in relation to extent of disease.
      DESIGN: Using a retrospective cohort design, changes in and predictors of lung
      function were evaluated. RESULTS: A total of 41 patients were included in the
      final analysis. The median decline in annualised forced expiratory volume in 1
      sec (FEV1) was 180.0 ml/year (95%CI 118.9-356.1) in advanced PTB and 94.7 ml/year
      (95%CI 33.4-147.3) in localised PTB (DeltaFEV1% predicted/year 9.4%, 95%CI 4.4
      14.0 vs. 3.8%, 95%CI 1.8-6.2). The median decline in annualised forced vital
      capacity (FVC) was 309.6 ml/year (95%CI 137.0-359.0) in advanced PTB and 101.1
      ml/year (95%CI 30.3-219.6) in localised PTB (DeltaFVC % predicted/year 7.3%,
      95%CI 5.3-12.3 vs. 2.9%, 95%CI 0.9-6.5). CONCLUSIONS: As the sample size of our
      study was small, the conclusions could be biased. Nevertheless, our findings show
      that PTB causes a significant decline in lung function even in localised PTB,
      whereas advanced PTB was associated with excessive or even higher decline. This
      study suggests that early diagnosis and treatment of PTB is needed to preserve
      lung function.

PMID- 25868028
TI  - Reduced sensitivity of the QuantiFERON((r)) test in diabetic patients with smear
      negative tuberculosis.
AB  - SETTING: Immunosuppressive conditions have been associated with low sensitivity
      of interferon-gamma release assays (IGRAs) and the tuberculin skin test (TST) for
      the diagnosis of tuberculosis (TB). However, no systematic analysis of patient
      and bacterial characteristics has been performed before. OBJECTIVE: To determine
      the sensitivity and the risk factors for false-negative QuantiFERON((r))-TB (QFT)
      assay and TST in TB patients. DESIGN: We performed a retrospective analysis of
      data collected in a community-based study of TB in San Francisco, CA, USA. We
      included 300 TB patients who underwent QFT and TST. RESULTS: The risk factors for
      false-negative QFT were human immunodeficiency virus infection and the use of
      QuantiFERON((r))-TB Gold. In patients with sputum smear-negative TB, diabetes
      mellitus (DM) was associated with false-negative QFT (OR 2.85, 95%CI 1.02-7.97, P
      = 0.045). TST sensitivity was higher than QFT sensitivity in DM patients (OR
      9.46, 95%CI 2.53-35.3). CONCLUSIONS: In San Francisco, QFT sensitivity was lower
      than that of TST, especially in patients with DM. Stratified analysis by sputum
      smear results showed that this association was specific to smear-negative TB. In
      contrast, TST was not affected by the presence of DM.

PMID- 25868030
TI  - Childhood tuberculosis and exposure to indoor air pollution: a systematic review
      and meta-analysis.
AB  - BACKGROUND: Indoor air pollution (IAP) from environmental tobacco smoke (ETS) and
      biomass fuel smoke (BMS) poses respiratory health risks, with children and women
      bearing the major burden. OBJECTIVES: We used a systematic review and meta
      analysis to investigate the relation between childhood tuberculosis (TB) and
      exposure to ETS and BMS. METHODS: We searched three databases for epidemiological
      studies that investigated the association of childhood TB with exposure to ETS
      and BMS. We calculated pooled estimates and heterogeneity for studies eligible
      for inclusion in the meta-analysis and stratified studies on ETS by outcome.
      RESULTS: Five case-control and three cross-sectional studies were eligible for
      inclusion in the meta-analysis and quality assessment. Pooled effect estimates
      showed that exposure to ETS is associated with tuberculous infection and TB
      disease (OR 1.9, 95%CI 1.4-2.9) among exposed compared to non-exposed children.
      TB disease in ETS studies produced a pooled OR of 2.8 (95%CI 0.9-4.8), which was
      higher than the OR for tuberculous infection (OR 1.9, 95%CI 0.9-2.9) for children
      exposed to ETS compared to non-exposed children. Studies on BMS exposure were too
      few and too small to permit a conclusion. CONCLUSION: Exposure to ETS increases
      the risk of childhood TB disease or tuberculous infection.

PMID- 25868031
TI  - Vertebral compression fractures may increase mortality in male patients with
      chronic obstructive pulmonary disease.
AB  - BACKGROUND: Vertebral compression fracture (VCF) is frequent in chronic
      obstructive pulmonary disease (COPD) patients. However, little is known about
      whether VCF affects mortality in COPD patients. OBJECTIVE: To investigate whether
      VCFs might increase death in COPD patients. METHODS: In this retrospective cohort
      study, we enrolled 254 COPD patients with a recent history of hospitalisation due
      to respiratory problems. Patients were assessed for VCF using quantitative
      morphometric analyses of lateral chest radiographs; 211 patients received follow
      up examinations for 2 years. RESULTS: Of the 211 COPD patients analysed, 60
      (28.4%) had VCF at enrolment. During the follow-up period, 33/60 (55.0%) patients
      with and 46/151 patients (30.5%) without VCF died (P = 0.003, log-rank test). Cox
      proportional hazard analysis revealed that VCF is an independent risk factor for
      death after adjusting for age, sex, body mass index, smoking, dyspnoea scale,
      forced expiratory volume in 1 sec (FEV1) and comorbidities (hazard ratio for VCF
      = 1.79, 95%CI 1.11-2.89, P = 0.02). CONCLUSION: VCF might be an independent risk
      factor for death in male COPD patients.

PMID- 25868032
TI  - Sputum bacteriology in steady-state bronchiectasis in Guangzhou, China.
AB  - BACKGROUND: The impact of potentially pathogenic micro-organisms (PPMs) on
      Chinese patients with steady-state bronchiectasis is unknown. METHODS: Peripheral
      blood and sputum were sampled to determine inflammatory markers and sputum
      bacterial density. Spirometry and diffusing capacity were measured. Quality of
      life was assessed using the St George's Respiratory Questionnaire. RESULTS: Of
      144 patients with steady-state bronchiectasis, Pseudomonas aeruginosa was
      isolated in 44 cases (30.6%). Compared with other PPMs, P. aeruginosa had a more
      pronounced influence on airway inflammation and spirometry, but not on systemic
      inflammation or quality of life. The impact of PPMs other than P. aeruginosa on
      clinical indices was similar. Bacterial density was not correlated with most
      clinical parameters. Factors associated with PPM isolation included
      bronchiectasis symptoms for ? 10 years (OR 2.13) and ? 4 bronchiectatic lobes (OR
      2.82). Having ? 4 exacerbations within 2 years (OR 2.18) and cystic
      bronchiectasis (OR 2.23) was associated with the colonisation of PPMs, i.e.,
      isolating an identical PPM on at least two occasions within 1 year. CONCLUSION:
      In patients with steady-state bronchiectasis in Guangzhou, P. aeruginosa is the
      most common organism causing heightened airway inflammation and poor lung
      function. PPM isolation or colonisation should be suspected in case of longer
      duration of symptoms, multilobar bronchiectasis, frequent exacerbation and cystic
      bronchiectasis.

PMID- 25868033
TI  - A prospective study of mycobacterial viability in refrigerated, unpreserved
      sputum batched for up to 8 weeks.

PMID- 25868034
TI  - Adverse drug reactions in tuberculosis patients: consequences for TB control.

PMID- 25868035
TI  - Consensus for nonmelanoma skin cancer treatment: basal cell carcinoma, including
      a cost analysis of treatment methods.
AB  - BACKGROUND: Basal cell carcinoma (BCC) is the most common cancer in the US
      population affecting approximately 2.8 million people per year. Basal cell
      carcinomas are usually slow-growing and rarely metastasize, but they do cause
      localized tissue destruction, compromised function, and cosmetic disfigurement.
      OBJECTIVE: To provide clinicians with guidelines for the management of BCC based
      on evidence from a comprehensive literature review, and consensus among the
      authors. MATERIALS AND METHODS: An extensive review of the medical literature was
      conducted to evaluate the optimal treatment methods for cutaneous BCC, taking
      into consideration cure rates, recurrence rates, aesthetic and functional
      outcomes, and cost-effectiveness of the procedures. RESULTS: Surgical approaches
      provide the best outcomes for BCCs. Mohs micrographic surgery provides the
      highest cure rates while maximizing tissue preservation, maintenance of function,
      and cosmesis. CONCLUSION: Mohs micrographic surgery is an efficient and cost
      effective procedure and remains the treatment of choice for high-risk BCCs and
      for those in cosmetically sensitive locations. Nonsurgical modalities may be used
      for low-risk BCCs when surgery is contraindicated or impractical, but the cure
      rates are lower.

PMID- 25868036
TI  - Isolation and culture of rat aortic valve interstitial cells.
AB  - OBJECTIVE: Culturing aortic valve interstitial cells is a useful way to
      investigate the physiology and pathology of the aortic valve at the cellular
      level. The culture methods of the cells have been established in many species.
      However, the previous methods need some improvements. METHODS: We evaluated
      various techniques with regard to the isolation of Sprague-Dawley (SD) rat aortic
      valve interstitial cells and established suitable conditions about the culture
      and passage of the primary cells. The specimens from the aortic valve were
      processed by tissue explant methods before seeding them onto the dishes. RESULTS:
      The cells obtained emerged from the explants after 2 to 3 days and stained
      positive for alpha-SMA and vimentin protein. Moreover, transmission electron
      microscopy images showed that the cells had abundant mitochondria, prominent
      rough endoplasmic reticulum, and plentiful myofilaments. CONCLUSION: In the
      present study, we provided reliable and efficient methods for the isolation and
      culture of rat aortic valve interstitial cells that could serve for in vitro
      studies on aortic valve physiology and pathophysiology.

PMID- 25868037
TI  - The effects of tirofiban infusion on clinical and angiographic outcomes of
      patients with STEMI undergoing primary PCI.
AB  - OBJECTIVE: The present study was designed to determine the effects of tirofiban
      (Tiro) infusion on angiographic measures, ST-segment resolution, and clinical
      outcomes in patients with STEMI undergoing PCI. Glycoprotein (GP) IIb/IIIa
      inhibitors are beneficial in ST-segment elevation myocardial infarction (STEMI)
      patients undergoing percutaneous coronary intervention (PCI), while the most
      effective timing of administration is still under investigation. METHODS: A total
      of 1242 patients (83.0% males, mean (standard deviation; SD) age: 54.7 (10.9)
      years) with STEMI who underwent primary PCI were included in this retrospective
      non-randomized study in four groups, composed of no tirofiban infusion [Tiro (-);
      n=248], tirofiban infusion before PCI (pre-Tiro; n=720), tirofiban infusion
      during PCI (peri-Tiro; n=50), and tirofiban infusion after PCI (post-Tiro;
      n=224). In all Tiro (+) patients, bolus administration of Tiro (10 ug/kg) was
      followed by infusion (0.15 ug/kg/min) for a mean (SD) duration of 22.4+/-6.8
      hours. RESULTS: The pre-PCI Tiro group was associated with the highest percentage
      of patients with TIMI 3 flow (99.4%; p<0.001), the lowest corrected TIMI frame
      count [21(18-23.4); p<0.001], the highest percentage of patients with >75% ST
      segment resolution (78.1%; p<0.001), and the lowest rate of in-hospital sudden
      cardiac death and in-hospital all-cause mortality (3.2%, p<0.05, 3.3%, p=0.01).
      Major bleeding was reported in 18 (1.8%) patients who received tirofiban.
      CONCLUSION: Use of standard-dose bolus tirofiban in addition to aspirin, high
      dose clopidogrel, and unfractionated heparin prior to primary PCI significantly
      improves myocardial reperfusion, ST-segment resolution, in-hospital mortality
      rate, and in-hospital sudden cardiac death in patients with STEMI with no
      increased risk of major bleeding.

PMID- 25868038
TI  - The evaluation of the clinical utility of urocortin 1 and adrenomedullin versus
      proBNP in systolic heart failure.
AB  - OBJECTIVE: Urocortin 1 (UCN1) has vasodilator, diuretic, and natriuretic effects,
      and its expression increases in heart failure (HF). Adrenomedullin (ADM)
      increases cardiac output and lowers blood pressure in healthy men and in patients
      with heart failure. The aim of the study was to determine UCN1 and ADM levels in
      patients with HF, to evaluate the relationship of UCN1 and ADM with various
      clinical parameters, and to assess UCN1 and ADM as diagnostic markers in HF, in
      comparison with pro-brain natriuretic peptide (pro-BNP). METHODS: We investigated
      serum levels of UCN1, ADM, and pro BNP in 86 consecutive patients with systolic
      HF [ejection fraction (EF) <=45%] and 85 healthy controls. Serum UCN1, ADM, and
      pro-BNP levels were measured with the ELISA method. Transthoracic
      echocardiography was performed to determine left ventricular EF and pulmonary
      artery systolic pressure. RESULTS: UCN1 and ADM levels were higher in HF patients
      (446.2+/-145.7 pg/mL, p<0.001; 87.9+/-4.2 pg/mL, p<0.001 respectively). UCN1 was
      positively correlated with pro-BNP (r=0.963, p<0.001), ADM (r=0.915, p<0.001),
      and NYHA (r=0.879, p<0.001); ADM was positively correlated with pro-BNP (r=0.956,
      p<0.001) and NYHA (r=0.944, p<0.001). Receiver operating characteristic curves
      yielded an area under the curve of 1.00 (p<0.001) for UCN1, 1.00 (p<0.001) for
      ADM, and 0.99 (p<0.001) for pro-BNP in the diagnosis of HF. CONCLUSION: UCN1 and
      ADM increase with worsening HF and left ventricular dysfunction. They may be used
      as diagnostic biomarkers in systolic HF, but the incremental value of measuring
      UCN1 and ADM in patients tested for pro-BNP is questionable.

PMID- 25868039
TI  - Chronic kidney disease: Prognostic marker of nonfatal pulmonary thromboembolism.
AB  - OBJECTIVE: Renal dysfunction is associated with increased cardiovascular
      morbidity and mortality. The alteration in renal function as a marker of
      mortality in pulmonary thromboembolism (PTE) has not been studied extensively.
      METHODS: Four hundred four consecutive patients diagnosed with non-high-risk PTE
      (without cardiogenic shock or blood pressure <90 mm Hg) were prospectively
      enrolled in the study between 2005-2010. Kidney function, based on glomerular
      filtration rate (GFR), calculated by the simplified modification in diet in renal
      disease (MDRD) equation (sMDRD); troponin I; B-type natriuretic peptide (BNP);
      and echocardiographic markers of right ventricular (RV) function were determined
      in survivors versus non-survivors after a 2-year follow-up. RESULTS: GFR was
      significantly lower in non-survivors than in survivors: 51.85+/-19.08 mL/min/1.73
      m2 and 71.65+/-23.21 mL/min/1.73 m2, respectively (p=0.000). The highest 2-year
      mortality rate (20%) was recorded in patients with moderate renal dysfunction
      associated with RV dysfunction. Using multivariate analysis, we found that GFR is
      an independent predictor of 2-year mortality (OR 0.973, 95% CI: 0.959-0.987,
      p=0.000), besides troponin I, dyslipidemia, acceleration time of pulmonary
      ejection, pericardial effusion, and BNP. CONCLUSION: The association of renal
      dysfunction with right ventricular dysfunction in patients with non-fatal
      pulmonary thromboembolism resulted in high mortality. Renal dysfunction, assessed
      by glomerular filtration rate, may be used in the risk stratification of patients
      with non-high-risk pulmonary thromboembolism, besides troponin I, BNP, and right
      ventricle echocardiographic dysfunction markers.

PMID- 25868040
TI  - High levels of HB-EGF and interleukin-18 are associated with a high risk of in
      stent restenosis.
AB  - OBJECTIVE: To explore the clinical significance of heparin-binding epidermal
      growth factor-like growth factor (HB-EGF), interleukin-18 (IL-18), and
      interleukin-10 (IL-10) in restenosis after percutaneous coronary intervention
      (PCI). METHODS: A total of 198 patients with acute coronary syndrome underwent
      coronary drug-eluting stent implantation and were divided into the restenosis
      group and non-restenosis group on the basis of second coronary angiography.
      Biological parameters and HB-EGF, IL-18, and IL-10 levels were measured. Patients
      in the restenosis group were further divided into 3 subgroups according to
      Gensini score: group A (Gensini score of <20), group B (Gensini score of >=20 but
      <40), and group C (Gensini score of >=40). RESULTS: Compared with the non
      restenosis group, HB-EGF and IL-18 levels were significantly higher but serum IL
      10 levels were significantly lower in the restenosis group. Furthermore, HB-EGF
      levels increased with the Gensini score among the 3 subgroups. Spearman's
      correlation analysis showed that HB-EGF levels were associated with IL-18 levels
      and the number of diseased vessels. Multivariate logistic regression analysis
      showed that diabetes, HB-EGF, and IL-18 were risk factors for restenosis [odds
      ratio with 95% confidence interval: 3.902 (1.188-4.415), 2.185 (1.103-4.014), and
      2.079 (1.208-4.027), respectively]. CONCLUSION: The present study has
      demonstrated that HB-EGF may be used to evaluate the severity of restenosis and
      coronary artery lesion and that inflammatory responses may be involved in the
      process of restenosis.

PMID- 25868041
TI  - Association between serum total antioxidant status and flow-mediated dilation in
      patients with systemic lupus erythematosus: an observational study.
AB  - OBJECTIVE: Endothelial dysfunction (ED) is a condition that involves increased
      oxidative stress and decreased total antioxidant status (TAS) levels. Systemic
      lupus erythematosus (SLE) is also associated with ED. We aimed to determine the
      association between serum TAS and ED as assessed by flow-mediated dilation (FMD)
      in patients with SLE. METHODS: Thirty-four patients with stable SLE who were not
      undergoing any treatment and 39 healthy volunteers without any overt
      cardiovascular disease were included in this cross-sectional study. Doppler
      ultrasound was used to measure FMD to assess ED in the study groups. Serum TAS
      levels were measured using a TAS kit. High-sensitivity C-reactive protein (hs
      CRP) and anticardiolipin antibody (aCLA) levels were also measured to assess the
      inflammatory state. The SLE group further was divided into 2 groups according to
      presence or absence of aCLA. SLE disease activity was assessed using the SLE
      disease activity index (SLEDAI). Regression analysis was used to define
      independent predictors. RESULTS: The mean TAS levels were significantly lower in
      patients with SLE than in controls (1.60+/-0.11 versus 1.73+/-0.15 mmol/L,
      p<0.001). hs-CRP levels were significantly higher in patients with SLE than in
      controls (8.2+/-6.0 vs. 2.9+/-4.0 mg/L; p<0.001), particularly in SLE patients
      with positive aCLA when compared with SLE patients with negative aCLA (13.8+/-4.3
      vs. 5.6+/-4.8 mg/L, p<0.001). The FMD percent was significantly lower in patients
      with SLE than in controls (8.1+/-4.9 vs. 10.6+/-4.7, p=0.04). There was a
      significant positive correlation between FMD and TAS in the SLE group (r=0.448,
      p=0.008) and the control group (r=0.367, p=0.03) and a significant negative
      correlation between FMD and serum hs-CRP (r=-0.368, p=0.04) in only the SLE
      group. In multiple linear regression analysis, TAS, hs-CRP, and SLEDAI were
      independently correlated with FMD (beta=0.50, p=0.003; beta=-0.33, p=0.03; and
      beta=-0.36, p=0.03; respectively). CONCLUSION: Patients with SLE who have no
      overt cardiovascular disease are at increased risk for ED and this may be
      associated with underlying inflammation and impairment of TAS.

PMID- 25868042
TI  - Acute effects of Red Bull energy drink on ventricular repolarization in healthy
      young volunteers: a prospective study.
AB  - OBJECTIVE: Energy drinks (EDs) are widely consumed products of the beverage
      industry and are often chosen by teenagers and young adults. Several adverse
      cardiovascular events and malignant cardiac arrhythmias following consumption of
      EDs have been reported in the literature. Several studies have suggested that the
      interval from the peak to the end of the electrocardiographic T wave (Tp-e) may
      correspond to the dispersion of repolarization and that an increased Tp-e
      interval and Tp-e/QT ratio are associated with malignant ventricular arrhythmias.
      This study investigated the acute effects of Red Bull ED on ventricular
      repolarization as assessed by the Tp-e interval and Tp-e/QT ratio. METHODS: A
      prospective, open-label study design was used. After an 8-h fast, 50 young,
      healthy subjects consumed 355 mL of Red Bull ED. The Tp-e interval, Tp-e/QTc
      ratio, and several other electrocardiographic parameters were measured at
      baseline and 2 h after ingestion of Red Bull ED. RESULTS: No significant changes
      in the Tp-e interval or Tp-e/QTc ratio were observed with Red Bull ED
      consumption. Red Bull ED consumption led to increases in both systolic and
      diastolic blood pressures, which were associated with an increased heart rate.
      CONCLUSION: Although ingestion of Red Bull ED increases the heart rate and
      diastolic and systolic blood pressures, it does not cause alterations in
      ventricular repolarization as assessed by the Tp-e interval and Tp-e/QTc ratio.

PMID- 25868043
TI  - A time differential staining technique coupled with full bilateral gill
      denervation to study ionocytes in fish.
AB  - Branchial ionocytes (ICs) are the functional units for ionic regulation in fish.
      In adults, they are found on the filamental and lamellar epithelia of the gill
      where they transport ions such as Na+, Cl- and Ca2+ via a variety of ion
      channels, pumps and exchangers. The teleost gill is extrinsically innervated by
      the facial (VI), glossopharyngeal (IX) and vagus (X) nerves. The IX and X nerves
      are also the extrinsic source of branchial IC innervation. Here, two techniques
      used to study the innervation, proliferation and distribution of ICs are
      described: a time differential staining technique and a full bilateral gill
      denervation technique. Briefly, goldfish are exposed to a vital mitochondrion
      specific dye (e.g., MitoTracker Red) which labels (red fluorescence) pre-existing
      ICs. Fish were either allowed to recover for 3-5 days or immediately underwent a
      full bilateral gill denervation. After 3-5 days of recovery, the gills are
      harvested and fixed for immunohistochemistry. The tissue is then stained with an
      alpha-5 primary antibody (targets Na+/K+ ATPase containing cells) in conjunction
      with a secondary antibody that labels all (both new and pre-existing) ICs green.
      Using confocal imaging, it was demonstrated that pre-existing ICs appear yellow
      (labelled with both a viable mitochondrion-specific dye and alpha-5) and new ICs
      appear green (labelled with alpha-5 only). Both techniques used in tandem can be
      applied to study the innervation, proliferation and distribution of ICs on the
      gill filament when fish are exposed to environmental challenges.

PMID- 25868045
TI  - Proceedings of the american burn association 47th annual meeting.

PMID- 25868044
TI  - Prevalence of illicit substance use among Arab adults in Israel: Findings from a
      national survey.
AB  - INTRODUCTION AND AIMS: The aim of this study was to examine illicit psychoactive
      substance use rates among adult Arabs in Israel. DESIGN AND METHODS: Cross
      sectional survey of 1200 Arab adults recruited nationwide via cluster sampling
      and interviewed using a structured questionnaire was conducted. RESULTS: Fourteen
      percent of respondents reporting illegal substance use with increased odds of use
      among males and those who were secular/not religious. DISCUSSION AND CONCLUSIONS:
      These findings show for the first time the extent of illegal substance use among
      Arab adults in Israel and suggest the possibility for targeted interventions in
      certain population groups.

PMID- 25868047
TI  - Solvothermally Synthesized Sb2Te3 Platelets Show Unexpected Optical Contrasts in
      Mid-Infrared Near-Field Scanning Microscopy.
AB  - We report nanoscale-resolved optical investigations on the local material
      properties of Sb2Te3 hexagonal platelets grown by solvothermal synthesis. Using
      mid-infrared near-field microscopy, we find a highly symmetric pattern, which is
      correlated to a growth spiral and which extends over the entire platelet. As the
      origin of the optical contrast, we identify domains with different densities of
      charge carriers. On Sb2Te3 samples grown by other means, we did not find a
      comparable domain structure. 

PMID- 25868048
TI  - Cation templating and electronic structure effects in uranyl cage clusters probed
      by the isolation of peroxide-bridged uranyl dimers.
AB  - The self-assembly of uranyl peroxide polyhedra into a rich family of nanoscale
      cage clusters is thought to be favored by cation templating effects and the
      pliability of the intrinsically bent U-O2-U dihedral angle. Herein, the
      importance of ligand and cationic effects on the U-O2-U dihedral angle were
      explored by studying a family of peroxide-bridged dimers of uranyl polyhedra.
      Four chemically distinct peroxide-bridged uranyl dimers were isolated that
      contain combinations of pyridine-2,6-dicarboxylate, picolinate, acetate, and
      oxalate as coordinating ligands. These dimers were synthesized with a variety of
      counterions, resulting in the crystallographic characterization of 15 different
      uranyl dimer compounds containing 17 symmetrically distinct dimers. Eleven of the
      dimers have U-O2-U dihedral angles in the expected range from 134.0 to 156.3
      degrees ; however, six have 180 degrees  U-O2-U dihedral angles, the first time
      this has been observed for peroxide-bridged uranyl dimers. The influence of
      crystal packing, countercation linkages, and pi-pi stacking impact the dihedral
      angle. Density functional theory calculations indicate that the ligand does not
      alter the electronic structure of these systems and that the U-O2-U bridge is
      highly pliable. Less than 3 kcal.mol(-1) is required to bend the U-O2-U bridge
      from its minimum energy configuration to a dihedral angle of 180 degrees . These
      results suggest that the energetic advantage of bending the U-O2-U dihedral angle
      of a peroxide-bridged uranyl dimer is at most a modest factor in favor of cage
      cluster formation. The role of counterions in stabilizing the formation of rings
      of uranyl ions, and ultimately their assembly into clusters, is at least as
      important as the energetic advantage of a bent U-O2-U interaction. 

PMID- 25868051
TI  - Erratum.

PMID- 25868052
TI  - Patients' experiences of clinicians' crying during psychotherapy for eating
      disorders.
AB  - Many psychotherapists have cried in a therapy session. Those clinicians who do
      cry see it as likely to have a positive impact on the therapy or to have no
      impact, and therapist personality characteristics have not shown reliable
      associations to crying in therapy. However, it is not known how patients
      experience therapists' crying, or whether the patient's view of the therapist's
      characteristics is related to that experience. This study used an online survey,
      recruiting 202 patients with eating disorders, 188 of whom had received therapy
      for an eating disorder, and 105 of whom had experienced a therapist crying.
      Retrospective data from those 105 individuals indicated that therapists' crying
      tended to be seen positively, by patients but that perception was influenced by
      the patients' perceptions of the demeanor of their therapist and their
      understanding of the meaning of the crying. Although they need to be extended to
      other disorders, these findings suggest that therapists' crying needs to be
      understood in the context of the therapist's perceived characteristics and
      demeanor, rather than being assumed to be positive or to have no impact on the
      therapy.

PMID- 25868050
TI  - Bone Morphogenetic Protein-4 (BMP4): A Paracrine Regulator of Human Adrenal C19
      Steroid Synthesis.
AB  - Bone morphogenetic proteins (BMPs) comprise one of the largest subgroups in the
      TGF-beta ligand superfamily. We have identified a functional BMP system equipped
      with the ligand (BMP4), receptors (BMP type II receptor, BMP type IA receptor,
      also called ALK3) and the signaling proteins, namely the mothers against
      decapentaplegic homologs 1, 4, and 5 in the human adrenal gland and the human
      adrenocortical cell line H295R. Microarray, quantitative RT-PCR, and
      immunohistochemistry confirmed that BMP4 expression was highest in the adrenal
      zona glomerulosa followed by the zona fasciculata and zona reticularis. Treatment
      of H295R cells with BMP4 caused phosphorylation of the mothers against
      decapentaplegic and a profound decrease in synthesis of the C19 steroids
      dehydroepiandrosterone (DHEA), DHEA sulfate, and androstenedione. Administration
      of BMP4 to cultures of H295R cells also caused a profound decrease in the mRNA
      and protein levels of 17alpha-hydroxylase/17,20-lyase (CYP17A1 and P450c17,
      respectively) but no significant effect on the mRNA levels of cholesterol side
      chain cleavage cytochrome P450 (CYP11A1) or type 2 3beta-hydroxysteroid
      dehydrogenase (HSD3B2). Furthermore, Noggin (a BMP inhibitor) was able to reverse
      the negative effects of BMP4 with respect to both CYP17A1 transcription and DHEA
      secretion in the H295R cell line. Collectively the present data suggest that BMP4
      is an autocrine/paracrine negative regulator of C19 steroid synthesis in the
      human adrenal and works by suppressing P450c17. 

PMID- 25868053
TI  - Clinicians' emotional responses and Psychodynamic Diagnostic Manual adult
      personality disorders: A clinically relevant empirical investigation.
AB  - The aim of this study is to explore the relationship between level of personality
      organization and type of personality disorder as assessed with the categories in
      the Psychodynamic Diagnostic Manual (PDM; PDM Task Force, 2006) and the emotional
      responses of treating clinicians. We asked 148 Italian clinicians to assess 1 of
      their adult patients in treatment for personality disorders with the
      Psychodiagnostic Chart (PDC; Gordon & Bornstein, 2012) and the Personality
      Diagnostic Prototype (PDP; Gazzillo, Lingiardi, & Del Corno, 2012) and to
      complete the Therapist Response Questionnaire (TRQ; Betan, Heim, Zittel-Conklin,
      & Westen, 2005). The patients' level of overall personality pathology was
      positively associated with helpless and overwhelmed responses in clinicians and
      negatively associated with positive emotional responses. A parental and
      disengaged response was associated with the depressive, anxious, and dependent
      personality disorders; an exclusively parental response with the phobic
      personality disorder; and a parental and criticized response with narcissistic
      disorder. Dissociative disorder evoked a helpless and parental response in the
      treating clinicians whereas somatizing disorder elicited a disengaged reaction.
      An overwhelmed and disengaged response was associated with sadistic and
      masochistic personality disorders, with the latter also associated with a
      parental and hostile/criticized reaction; an exclusively overwhelmed response
      with psychopathic patients; and a helpless response with paranoid patients.
      Finally, patients with histrionic personality disorder evoked an overwhelmed and
      sexualized response in their clinicians whereas there was no specific emotional
      reaction associated with the schizoid and the obsessive-compulsive disorders.
      Clinical implications of these findings were discussed.

PMID- 25868054
TI  - The feedback whirlpool of early childhood sleep and behavior problems.

PMID- 25868055
TI  - The prevalence of phenotypic silver resistance in clinical isolates.
AB  - Research has shown silver to be an effective antimicrobial agent against
      bacteria, virus, yeast, and fungi. Due to the increased use of silver-based wound
      products during the past decade, concerns of widespread silver resistance have
      been raised.1 The purpose of this study was to assess the prevalence of
      phenotypic silver resistance in clinical isolates. METHODS: A total of 130
      different microorganism strains were collected from patients admitted to a
      tertiary care hospital. To determine phenotypic silver resistance, a corrected
      zone of inhibition (CZOI) test was used. The isolate (0.1 mL) was streaked on
      nutrient agar in 3 directions to form a confluent lawn. A silver dressing and a
      control gauze dressing were placed on the lawn and incubated for 24 hours. The
      CZOI was determined by averaging the zone of clearance in both directions across
      the dressing and then subtracting the dressing size. Corrected zone of inhibition
      tests were conducted in duplicate. To confirm the silver dressing killed the
      microorganism and did not simply hinder bacterial growth, a culture was taken
      from underneath each silver dressing and plated separately. RESULTS: All of the
      isolates showed no growth when tested against the silver-based dressing. The CZOI
      values ranged between 0.0 mm and 7.25 mm. No growth was observed in the secondary
      culture from underneath the dressing, indicating the silver dressing was
      bactericidal for all 130 isolates tested and not simply bacteriostatic. The
      control gauze dressing did not show any antimicrobial properties. CONCLUSION: The
      threat of widespread silver resistance in clinical isolates remains low. However,
      continued monitoring for silver resistance should be maintained.

PMID- 25868056
TI  - Management of skin grafts using negative pressure therapy: the effect of varied
      pressure on skin graft incorporation.
AB  - INTRODUCTION: Optimal pressure settings have been suggested in the use of
      negative pressure wound therapy (NPWT) in wound dressings. When used as a bolster
      for skin grafting, an NPWT setting of 125 mm Hg was initially suggested, but not
      validated through studies. The objective of this study is to report findings on
      the effect of varied pressure settings on the incorporation of split thickness
      skin grafts when using an NPWT bolster. METHODS: From 2007 to 2010, 48 inpatients
      underwent split thickness skin grafting using a negative pressure system as a
      bolster under the care of 2 surgeons at 2 academic institutions. Twenty-two
      patients were evaluated retrospectively who were treated using NPWT bolsters at
      75 mm Hg and 125 mm Hg based on the surgeon's discretion. Twenty-six patients
      were evaluated prospectively and were randomized to 50 mm Hg, 75 mm Hg, 100 mm
      Hg, and 125 mm Hg pressure settings. Graft incorporation was assessed at time of
      bolster removal, 2 weeks, and 4 weeks, per standard protocol. RESULTS: At each
      assessment point, incorporation of each skin graft was > 95% in all study
      subjects, at all pressure settings. CONCLUSION: Whereas initially postulated to
      be 125 mm Hg, ideal pressure settings for NPWT, when used as a bolster for split
      thickness skin grafts, may be lower. This study suggests that pressures as low as
      50 mm Hg can be tolerated without compromise of skin graft incorporation. Study
      findings were presented at the Plastic Surgery Research Council Meeting in San
      Francisco, CA in April of 2010.    .

PMID- 25868057
TI  - Microclimate impact of prophylactic dressings using in vitro body analog method.
AB  - Wound dressings have been successfully explored for use in prevention of pressure
      ulcers in individuals who are at clinical high-risk for developing ulcers.
      METHODS: In this study, application of a recently described body analog test
      fixture and method is used to evaluate performance features of 8 clinically
      available dressings for prophylaxis. Documenting dressing performance is
      essential to defining the proper use and limits to application of dressings for
      ulcer prevention. These in vitro studies were undertaken to characterize the
      impact on the microclimate generated by the application of a dressing to the
      surface of the skin. RESULTS: The measurement of moisture trapped next to the
      skin, moisture escaped from the dressing, and heat trapped by the dressing show
      that some dressings are more suited for skin protection. CONCLUSION: It is
      evident that an optimal performance band for microclimate management exists in
      the application of dressings for prophylaxis, and that dressings should be
      evaluated for proper performance prior to implementation in a pressure ulcer
      prevention program.  .

PMID- 25868058
TI  - Effects of mucoadhessive paste of chlorhexidine and betamethasone on oral ulcer
      recovery process in rats.
AB  - INTRODUCTION: Ulcers are one of the most frequent conditions affecting the oral
      cavity. The aim of this study was to assess the effects of chlorhexidine and
      betamethasone on oral mucosa wound healing in rats. MATERIALS AND METHODS: In
      this study, adult male rats were used in 5 groups (n = 16 per group):
      bethamethasone (B); chlorhexidine (CHX); betamethasone and chlorhexidine (BC);
      control (C) no drugs; and blank (BB). A wound measuring 2 mm in diameter was
      punched into the hard palate of each rat. A mucosal defect measuring 2 mm in
      diameter and 0.2 mm in wall thickness was made to the depth of the periosteum in
      the palate with a round stainless steel blade designed for punch biopsy. For
      topical application, a swab was soaked in the appropriate study material and
      packed into the wound. The control group was not treated. Histological samples
      were harvested on post-injury days 2, 4, 6, and 8. RESULTS: Comparison of
      clinical size of wound showed that groups B and BC had the greatest reduction in
      wound size on days 4, 6, and 8. A higher count of polymorphonuclear cells was
      observed on days 2 and 4 in groups BB, CHX, and C. A lower count of mononuclear
      cells in group BC on days 6 and 8, compared to other groups, was also observed.
      Groups B and BC showed the highest fibroblast counts at all the intervals, with
      significant differences between the groups (P < 0.05). The inflammation score was
      highest at all the intervals in group C. The highest thickness of epithelium was
      observed in groups B and BC on days 6 and 8, which was significantly different
      from the other groups (P < 0.05). CONCLUSION: The results of this study showed
      the best wound healing processes from clinical and histological aspects in the B
      and BC groups. Chlorhexidine alone had no significant effect on wound healing and
      was not an effective drug alone.    .

PMID- 25868059
TI  - Effects of zinc supplementation on markers of insulin resistance and lipid
      profiles in women with polycystic ovary syndrome: a randomized, double-blind,
      placebo-controlled trial.
AB  - OBJECTIVE: This study was conducted to evaluate the effects of zinc
      supplementation on glucose homeostasis parameters and lipid concentrations in
      PCOS women. We are aware of no study evaluating the effects of zinc
      supplementation on metabolic profiles of patients with polycystic ovary syndrome
      (PCOS). METHODS: This randomized, double-blind, placebo-controlled trial was
      conducted among 52 women diagnosed with PCOS and aged 18-40 years old.
      Participants were randomly divided into 2 groups to receive 220 mg zinc sulfate
      (containing 50 mg zinc) supplements (n=26) or placebo (n=26) per day for 8 weeks.
      Fasting blood samples were taken at baseline and after 8 weeks' intervention to
      quantify glucose, insulin and lipid concentrations. RESULTS: After 8 weeks of
      intervention, subjects who received zinc supplements had significantly increased
      serum zinc levels (+15.6+/-21.8 vs. -4.1+/-16.7 mg/dL, P=0.001) compared with
      placebo. In addition, zinc-supplemented patients had reduced fasting plasma
      glucose (FPG) (-4.3+/-9.6 vs. +0.5+/-6.0 mg/dL, P=0.03), serum insulin levels (
      3.0+/-2.9 vs. +1.5+/-8.4 uIU/mL, P=0.01), homeostasis model of assessment-insulin
      resistance (HOMA-IR) (-0.8+/-0.8 vs. +0.3+/-1.9, P=0.006), homeostatic model
      assessment-Beta cell function (HOMA-B) (-10.6+/-9.5 vs. +4.9+/-32.1, P=0.02) and
      increased quantitative insulin sensitivity check index (QUICKI) (+0.02+/-0.02 vs.
      -0.004+/-0.05, P=0.03) compared with placebo. Additionally, a significant
      reduction in serum triglycerides (-15.6+/-40.3 vs. +14.5+/-25.3 mg/dL, P=0.002)
      and VLDL-cholesterol concentrations (-3.2+/-8.1 vs. +2.9+/-5.1 mg/dL, P=0.002)
      was observed following the administration of zinc supplements compared with
      placebo. CONCLUSION: Taken together, 220 mg zinc sulfate supplementation per day
      for 8 weeks among PCOS women had beneficial effects on metabolic profiles.

PMID- 25868060
TI  - Evaluation of cognitive functions in gestational diabetes mellitus.
AB  - OBJECTIVE: To evaluate the association between cognitive functions and metabolic
      status in cases with gestational diabetes mellitus (GDM). METHODS: In this study
      44 patients with GDM and 45 normal pregnant were included. Depression was
      evaluated with Beck's depression inventory (BDI). Cognitive functions were
      evaluated with Montreal cognitive assessment (MOCA), paced auditory serial
      addition test (PASAT), spatial recall test (SRT), symbol digit modalities (SDMT),
      and word list generation (WLG). RESULTS: The mean gestational age, educational
      level and account of previous birth of the subjects in the study were not
      statistically different between the groups. The mean scores of BDI of the 2
      groups were not statistically different. MOCA score and SDMT was significantly
      decreased in GDM in comparison to NP (p=0.005, p=0.04 respectively). Also, SDMT
      score was inversely correlated with number of pregnancies, postprandial blood
      glucose and HbA1c.The scores of PASAT, SRT, SPART and WLG were statistically
      similar between the groups. CONCLUSIONS: Our findings may be a clue for early
      onset of impairment in cognitive functions in cases with new onset diabetes
      during pregnancy.

PMID- 25868061
TI  - Expression of the central obesity and Type 2 Diabetes mellitus genes is
      associated with insulin resistance in young obese children.
AB  - OBJECTIVES: The assessment of the health consequences associated with obesity in
      young children is challenging. The aims of this study were: (1) to compare
      insulin resistance indices derived from OGTT in obese patients and healthy
      control (2) to analyze central obesity and Type 2 Diabetes genes expression in
      obese children, with special attention to the youngest group (< 10 years old).
      PATIENTS AND METHODS: The study included 49 children with obesity (median age
      13.5 years old), and 25 healthy peers. Biochemical blood tests and expression of
      11 central obesity and 33 Type 2 Diabetes genes was assessed. RESULTS: A
      significant difference in insulin resistance between obese and non-obese
      adolescents was observed in all studied indices (mean values of the insulin
      levels: 24.9 vs. 9.71 mIU/L in T0, 128 vs. 54.7 mIU/L in T60 and 98.7 vs. 41.1
      mIU/L in T120 respectively; AUC: 217 vs. 77.2 ng/ml*h, mean values of B% (state
      beta cell function), S% (insulin sensitivity), and IR were 255 (+/-97) vs. 135
      (+/-37.8), 46.6 (+/-37.3) vs. 84.2 (+/-29.6) and 3 (+/-1.55) vs. 1.36 (+/-0,56);
      HIS, WBIS and ISIBel median 3.89, 44.7, 0.73 vs. 8.57, 110, 2.25. All comparisons
      differed significantly p<0.001). Moreover, insulin sensitivity was significantly
      better in the older obese group (>10 years old): median AUC 239 vs. 104 ng/ml*h,
      and HIS, WBIS and ISIBel 3.57, 38, 0.67 vs. 6.23, 75.6, 1.87 respectively in the
      obese older compared to the obese younger subgroup, p<0.05. The expression of 64%
      of the central obesity genes and 70% of Type 2 Diabetes genes was higher in the
      obese compared to control groups. The differences were more pronounced in the
      younger obese group. CONCLUSION: Insulin resistance may develop in early stage of
      childhood obesity and in very young children may be associated with higher
      expression of the central obesity and Type 2 Diabetes genes.

PMID- 25868063
TI  - Characterization of feline serum-cobalt binding.
AB  - BACKGROUND: Oxidative stress inhibits albumin's ability to complex with cobalt.
      Feline serum-cobalt binding has not been described. OBJECTIVES: The objective was
      to develop a cobalt binding test for use with feline serum, and correlate the
      results with other biochemical and cellular constituents in blood, and with
      clinical diseases of cats. METHODS: A colorimetric test of cobalt binding, based
      on the oxidation-reduction reaction of Co(+2) and dithiothreitol, was developed
      using feline serum. The test was used to measure cobalt binding in stored serum
      from 176 cats presented to the University of Illinois Veterinary Teaching
      Hospital for a variety of disease conditions. Time-matched hematology and
      biochemical data, and clinical information, were obtained from the medical record
      of each cat and correlated with the serum-cobalt binding results. RESULTS: Serial
      dilution of feline serum with phosphate-buffered saline resulted in a highly
      linear decrease in serum-cobalt binding (r(2)  = .9984). Serum-cobalt binding of
      the clinical samples also correlated with albumin concentrations in a stepwise
      linear regression model (r(2)  = .425), and both cobalt binding and albumin were
      significantly decreased in cases of inflammation. Albumin and cobalt binding also
      shared significant correlations with several erythron variables, and serum
      concentration of total calcium and bilirubin. CONCLUSIONS: The correlation of
      cobalt binding measured by a colorimetric test with albumin concentration in the
      clinical samples and with serum dilution is consistent with feline albumin-cobalt
      complex formation. Hypoalbuminemia is the likely cause of reduced serum-cobalt
      binding in inflammation and the correlations observed between cobalt binding and
      other variables.

PMID- 25868064
TI  - Patients' experiences of technology and care in adult intensive care.
AB  - AIMS: To investigate patients' experiences of technology in an adult intensive
      care unit. BACKGROUND: Technology is fundamental to support physical recovery
      from critical illness in Intensive Care Units. As well as physical corollaries,
      psychological disturbances are reported in critically ill patients at all stages
      of their illness and recovery. Nurses play a key role in the physical and
      psychological care of patients;, however, there is a suggestion in the literature
      that the presence of technology may dehumanise patient care and distract the
      nurse from attending to patients psychosocial needs. Little attention has been
      paid to patients' perceptions of receiving care in a technological environment.
      DESIGN: This study was informed by Heideggerian phenomenology. METHODS: The
      research took place in 2009-2011 in a university hospital in England. Nineteen
      participants who had been patients in ICU were interviewed guided by an interview
      topic prompt list. Interviews were transcribed verbatim and analysed using Van
      Manen's framework. FINDINGS: Participants described technology and care as
      inseparable and presented their experiences as a unified encounter. The theme
      'Getting on with it' described how participants endured technology by 'Being
      Good' and 'Being Invisible'. 'Getting over it' described why participants endured
      technology by 'Bowing to Authority' and viewing invasive technologies as a
      'Necessary Evil'. CONCLUSION: Patients experienced technology and care as a
      series of paradoxical relationships: alienating yet reassuring, uncomfortable yet
      comforting, impersonal yet personal. By maintaining a close and supportive
      presence and providing personal comfort and care nurses may minimize the invasive
      and isolating potential of technology.

PMID- 25868065
TI  - Preparation and reactivity of gasless nanostructured energetic materials.
AB  - High-Energy Ball Milling (HEBM) is a ball milling process where a powder mixture
      placed in the ball mill is subjected to high-energy collisions from the balls.
      Among other applications, it is a versatile technique that allows for effective
      preparation of gasless reactive nanostructured materials with high energy density
      per volume (Ni+Al, Ta+C, Ti+C). The structural transformations of reactive media,
      which take place during HEBM, define the reaction mechanism in the produced
      energetic composites. Varying the processing conditions permits fine tuning of
      the milling-induced microstructures of the fabricated composite particles. In
      turn, the reactivity, i.e., self-ignition temperature, ignition delay time, as
      well as reaction kinetics, of high energy density materials depends on its
      microstructure. Analysis of the milling-induced microstructures suggests that the
      formation of fresh oxygen-free intimate high surface area contacts between the
      reagents is responsible for the enhancement of their reactivity. This manifests
      itself in a reduction of ignition temperature and delay time, an increased rate
      of chemical reaction, and an overall decrease of the effective activation energy
      of the reaction. The protocol provides a detailed description for the preparation
      of reactive nanocomposites with tailored microstructure using short-term HEBM
      method. It also describes a high-speed thermal imaging technique to determine the
      ignition/combustion characteristics of the energetic materials. The protocol can
      be adapted to preparation and characterization of a variety of nanostructured
      energetic composites. 

PMID- 25868062
TI  - Dynamic metabolic engineering: New strategies for developing responsive cell
      factories.
AB  - Metabolic engineering strategies have enabled improvements in yield and titer for
      a variety of valuable small molecules produced naturally in microorganisms, as
      well as those produced via heterologous pathways. Typically, the approaches have
      been focused on up- and downregulation of genes to redistribute steady-state
      pathway fluxes, but more recently a number of groups have developed strategies
      for dynamic regulation, which allows rebalancing of fluxes according to changing
      conditions in the cell or the fermentation medium. This review highlights some of
      the recently published work related to dynamic metabolic engineering strategies
      and explores how advances in high-throughput screening and synthetic biology can
      support development of new dynamic systems. Dynamic gene expression profiles
      allow trade-offs between growth and production to be better managed and can help
      avoid build-up of undesired intermediates. The implementation is more complex
      relative to static control, but advances in screening techniques and DNA
      synthesis will continue to drive innovation in this field. 

PMID- 25868066
TI  - The relationship between physical characteristics and match performance in rugby
      sevens.
AB  - Rugby sevens is a sport that requires a multitude of well-developed physical
      fitness qualities. Understanding the degree to which different physical
      characteristics relate to match performance provides practitioners with useful
      information for training programme design. Therefore, the aim of this study was
      to assess the relationship between physical characteristics and activities
      related to success in rugby sevens matches. Fitness test and match activity data
      were collected from 40 international and provincial rugby sevens players. Sprint
      speed over 10 m and 40 m had moderate to large (0.32-0.51) negative correlations
      (r) with line breaks, defenders beaten and tackle effectiveness. Repeated sprint
      ability and maximal aerobic capacity were moderately related to a measure of work
      rate (~0.38). Mixed-model analysis revealed a decrease of two between-player
      standard deviations in 10 m sprint time to be associated with an increase of 74%
      more line breaks per match. The results of this study suggest multiple physical
      characteristics are related to match performance in rugby sevens. 

PMID- 25868067
TI  - Association of Myxovirus Resistance Gene Promoter Polymorphism with Response to
      Combined Interferon Treatment and Progression of Liver Disease in Chronic HCV
      Egyptian Patients.
AB  - To evaluate the frequency of single-nucleotide polymorphism at the -88 myxovirus
      resistance (MxA) gene promoter region in relation to the status of hepatitis C
      virus (HCV) progression and response to combined interferon (IFN) in chronic HCV
      Egyptian patients. One hundred ten subjects were enrolled in the study; 60 HCV
      genotype 4-infected patients who underwent combined IFN therapy and 50 healthy
      individuals. All subjects were genotyped for -88 MxA polymorphism by the
      restriction fragment length polymorphism technique. There was an increasing trend
      of response to combined IFN treatment as 34.9% of GG, 64.3% of GT, and 66.7% of
      TT genotypes were sustained responders (P=0.05). The T allele was significantly
      affecting the response rate more than G allele (P=0.032). Moreover, the hepatic
      fibrosis score and hepatitis activity were higher in GG genotypes compared with
      the GT and TT genotypes. The multivariate analysis showed that the MxA GG
      genotype was an independent factor increasing the no response to IFN therapy
      (P=0.04, odds ratio [OR] 3.822, 95% confidence interval [CI] 1.056-11.092), also
      MxA G allele (P=0.0372, OR 2.905, 95% CI 1.066-7.919). MxA -88 polymorphism might
      be a potential biomarker to predict response to IFN and disease progression in
      chronic HCV-infected patients. 

PMID- 25868068
TI  - James B. Longley, Ph.d. 1920 - 2014.

PMID- 25868069
TI  - Prediction of smoking cessation with treatment: the emerging contribution of
      brain imaging research.

PMID- 25868070
TI  - T76. Baclofen as a pharmacotherapy for the treatment of concurrent alcohol and
      nicotine dependence: a double-blind, placebo-controlled, randomized trial.

PMID- 25868071
TI  - A new era of global surgery.

PMID- 25868072
TI  - Magnetic sentinel node and occult lesion localization in breast cancer (MagSNOLL
      Trial).
AB  - BACKGROUND: Non-palpable breast cancers require localization-guided surgery and
      axillary staging using sentinel lymph node biopsy (SLNB). This study investigated
      the novel technique of magnetic-guided lesion localization and concurrent SLNB,
      which avoids the need for wire-guided localization and radioisotopes. METHODS: An
      ultrasound-guided intratumoral injection of magnetic tracer (0.5 ml) was
      performed in a protocol-driven predefined minimum of ten patients with palpable
      breast cancer to assess the ability of the magnetic tracer safely to localize the
      tumour at the site of injection and concurrently drain to the lymphatics. Once
      successful lesion localization had been confirmed (peak magnetometer count
      retained at the centre of the tumour), the technique was undertaken in a further
      20 patients with non-palpable breast cancers awaiting wide local excision and
      SLNB. All patients underwent SLNB with both the magnetic and standard dual
      (radioisotope and Patent Blue V dye) techniques. RESULTS: Thirty-two patients
      were recruited, of whom 12 (1 with bilateral disease) presented with palpable and
      20 with non-palpable breast cancer. Peak magnetometer counts were retained at the
      tumour centre in all palpable (13) and non-palpable (20) breast cancers. Re
      excisions for involved margins were necessary in two patients with non-palpable
      breast cancers. The sentinel lymph node identification rates were 28 of 33
      procedures for the magnetic technique alone, 32 of 33 for the magnetic technique
      combined with blue dye, and 32 of 33 for the standard dual technique. CONCLUSION:
      Magnetic lesion localization is feasible, with intratumoral magnetic tracer
      injection combined with a periareolar injection of blue dye for subsequent SNLB.

PMID- 25868075
TI  - USE OF CONTRAST-ENHANCED COMPUTED TOMOGRAPHY TO STUDY THE CRANIAL MIGRATION OF A
      LUMBOSACRAL INJECTATE IN CADAVER DOGS.
AB  - Volumes used in lumbosacral epidural injections for anesthesia have remained
      unchanged since the 1960s. The goals of this cross-sectional observational study
      were to characterize the three-dimensional spread of a lumbosacral epidural
      injection, as well as confirm that the commonly used volume of 0.2 ml/kg injected
      into the lumbosacral epidural space reaches the thoracolumbar (TL) junction in
      the majority (>=80%) of dogs. Ten clinically normal, adult, nonpregnant, mixed
      breed dogs were obtained within five minutes of euthanasia and 0.2 ml/kg of
      radiopaque contrast medium was injected into the lumbosacral epidural space. A
      computed tomography scan of the TL spine was performed immediately following the
      injection. Migration of contrast reached the TL junction in 8 of 10 (80%) dogs.
      Contrast was well visualized in all epidural planes with contrast travelling
      predominantly in the dorsal epidural space in 7 of 10 (70%) dogs. There was no
      significant difference in the weight of dogs where the epidural injectate reached
      the TL junction and those where it did not (P = 0.16), or in the weight of dogs
      where the cranial-most point of the contrast column was in the dorsal versus the
      ventral epidural space (P = 0.32). This preliminary study supports the use of
      computed tomography to characterize injectate distribution in the canine
      thoracolumbar epidural space and provides evidence that a 0.2-ml/kg volume is
      likely to reache the TL junction in most dogs. Further studies are needed in live
      dogs to determine if variables affecting human epidural injectate doses have
      similar effects in the dog. 

PMID- 25868076
TI  - Albrecht Berkessel.

PMID- 25868077
TI  - Lipid trafficking at endoplasmic reticulum-chloroplast membrane contact sites.
AB  - Glycerolipid synthesis in plant cells is characterized by an intense trafficking
      of lipids between the endoplasmic reticulum (ER) and chloroplasts. Initially,
      fatty acids are synthesized within chloroplasts and are exported to the ER where
      they are used to build up phospholipids and triacylglycerol. Ultimately,
      derivatives of these phospholipids return to chloroplasts to form galactolipids,
      monogalactosyldiacylglycerol and digalactosyldiacylglycerol, the main and
      essential lipids of photosynthetic membranes. Lipid trafficking was proposed to
      transit through membrane contact sites (MCSs) connecting both organelles. Here,
      we review recent insights into ER-chloroplast MCSs and lipid trafficking between
      chloroplasts and the ER. 

PMID- 25868078
TI  - A novel method for constructing a WIFI positioning system with efficient
      manpower.
AB  - With the rapid development of WIFI technology, WIFI-based indoor positioning
      technology has been widely studied for location-based services. To solve the
      problems related to the signal strength database adopted in the widely used
      fingerprint positioning technology, we first introduce a new system framework in
      this paper, which includes a modified AP firmware and some cheap self-made WIFI
      sensor anchors. The periodically scanned reports regarding the neighboring APs
      and sensor anchors are sent to the positioning server and serve as the
      calibration points. Besides the calculation of correlations between the target
      points and the neighboring calibration points, we take full advantage of the
      important but easily overlooked feature that the signal attenuation model varies
      in different regions in the regression algorithm to get more accurate results.
      Thus, a novel method called RSSI Geography Weighted Regression (RGWR) is proposed
      to solve the fingerprint database construction problem. The average error of all
      the calibration points' self-localization results will help to make the final
      decision of whether the database is the latest or has to be updated
      automatically. The effects of anchors on system performance are further
      researched to conclude that the anchors should be deployed at the locations that
      stand for the features of RSSI distributions. The proposed system is convenient
      for the establishment of practical positioning system and extensive experiments
      have been performed to validate that the proposed method is robust and manpower
      efficient. 

PMID- 25868079
TI  - Georeferenced scanning system to estimate the leaf wall area in tree crops.
AB  - This paper presents the use of a terrestrial light detection and ranging (LiDAR)
      system to scan the vegetation of tree crops to estimate the so-called pixelated
      leaf wall area (PLWA). Scanning rows laterally and considering only the half
      canopy vegetation to the line of the trunks, PLWA refers to the vertical
      projected area without gaps detected by LiDAR. As defined, PLWA may be different
      depending on the side from which the LiDAR is applied. The system is completed by
      a real-time kinematic global positioning system (RTK-GPS) sensor and an inertial
      measurement unit (IMU) sensor for positioning. At the end, a total leaf wall area
      (LWA) is computed and assigned to the X, Y position of each vertical scan. The
      final value of the area depends on the distance between two consecutive scans (or
      horizontal resolution), as well as the number of intercepted points within each
      scan, since PLWA is only computed when the laser beam detects vegetation. To
      verify system performance, tests were conducted related to the georeferencing
      task and synchronization problems between GPS time and central processing unit
      (CPU) time. Despite this, the overall accuracy of the system is generally
      acceptable. The Leaf Area Index (LAI) can then be estimated using PLWA as an
      explanatory variable in appropriate linear regression models. 

PMID- 25868080
TI  - The effect of a widespread cancer-causing mutation on the inactive to active
      dynamics of the B-Raf kinase.
AB  - Protein kinases play a key role in regulating cellular processes. Kinase
      dysfunction can lead to disease, making them an attractive target for drug
      design. The B-Raf kinase is a key target for the treatment of melanoma since a
      single mutation (V600E) is found in more than 50% of all malignant melanomas.
      Despite the importance of B-Raf in melanoma treatment, the molecular mechanism by
      which the mutation increases kinase activity remains elusive. Since kinases are
      tightly regulated by a conformational transition between an active and inactive
      state, which is difficult to capture experimentally, large-scale enhanced
      sampling simulations are performed to examine the mechanism by which the V600E
      mutation enhances the activity of the B-Raf monomer. The results reveal that the
      mutation has a twofold effect. First, the mutation increases the barrier of the
      active to inactive transition trapping B-Raf in the active state. The mutation
      also increases the flexibility of the activation loop which might speed-up the
      rate-limiting step of phosphorylation. Both effects can be explained by the
      formation of salt-bridges with the Glu600 residue. 

PMID- 25868081
TI  - Neural activity propagation in an unfolded hippocampal preparation with a
      penetrating micro-electrode array.
AB  - This protocol describes a method for preparing a new in vitro flat hippocampus
      preparation combined with a micro-machined array to map neural activity in the
      hippocampus. The transverse hippocampal slice preparation is the most common
      tissue preparation to study hippocampus electrophysiology. A longitudinal
      hippocampal slice was also developed in order to investigate longitudinal
      connections in the hippocampus. The intact mouse hippocampus can also be
      maintained in vitro because its thickness allows adequate oxygen diffusion.
      However, these three preparations do not provide direct access to neural
      propagation since some of the tissue is either missing or folded. The unfolded
      intact hippocampus provides both transverse and longitudinal connections in a
      flat configuration for direct access to the tissue to analyze the full extent of
      signal propagation in the hippocampus in vitro. In order to effectively monitor
      the neural activity from the cell layer, a custom made penetrating micro
      electrode array (PMEA) was fabricated and applied to the unfolded hippocampus.
      The PMEA with 64 electrodes of 200 um in height could record neural activity deep
      inside the mouse hippocampus. The unique combination of an unfolded hippocampal
      preparation and the PMEA provides a new in-vitro tool to study the speed and
      direction of propagation of neural activity in the two-dimensional CA1-CA3
      regions of the hippocampus with a high signal to noise ratio. 

PMID- 25868082
TI  - Blood-brain barrier in health and disease.

PMID- 25868083
TI  - Editorial: rapid growth in the field of lymphatic biology.

PMID- 25868084
TI  - Impairment of adenylyl cyclase-mediated glutamatergic synaptic plasticity in the
      periaqueductal grey in a rat model of neuropathic pain.
AB  - KEY POINTS: Long-lasting neuropathic pain has been attributed to elevated
      neuronal plasticity changes in spinal, peripheral and cortical levels. Here, we
      found that reduced neuronal plasticity in the ventrolateral periaqueductal grey
      (vlPAG), a midbrain region important for initiating descending pain inhibition,
      may also contribute to neuropathic pain. Forskolin- and isoproterenol
      (isoprenaline)-elicited EPSC potentiation was impaired in the vlPAG of a rat
      model of neuropathic pain induced by spinal nerve injury. Down-regulation of
      adenylyl cyclase-cAMP- PKA signalling, due to impaired adenylyl cyclase, but not
      phosphodiesterase, in glutamatergic terminals may contribute to the hypofunction
      of excitatory synaptic plasticity in the vlPAG of neuropathic rats and the
      subsequent descending pain inhibition, ultimately leading to long-lasting
      neuropathic pain. Our results suggest that drugs that activate adenylyl cyclase
      in the vlPAG have the potential for relieving neuropathic pain. ABSTRACT:
      Neuropathic pain has been attributed to nerve injury-induced elevation of
      peripheral neuronal discharges and spinal excitatory synaptic plasticity while
      little is known about the contribution of neuroplasticity changes in the
      brainstem. Here, we examined synaptic plasticity changes in the ventrolateral
      (vl) periaqueductal grey (PAG), a crucial midbrain region for initiating
      descending pain inhibition, in spinal nerve ligation (SNL)-induced neuropathic
      rats. In vlPAG slices of sham-operated rats, forskolin, an adenylyl cyclase (AC)
      activator, produced long-lasting enhancement of EPSCs. This is a presynaptic
      effect since forskolin decreased the paired-pulse ratio and failure rate of
      EPSCs, and increased the frequency, but not the amplitude, of miniature EPSCs.
      Forskolin-induced EPSC potentiation was mimicked by a beta-adrenergic agonist
      (isoproterenol (isoprenaline)), and prevented by an AC inhibitor (SQ 22536) and a
      cAMP-dependent protein kinase (PKA) inhibitor (H89), but not by a
      phosphodiesterase (PDE) inhibitor (Ro 20-1724) or an A1 -adenosine antagonist
      (DPCPX). Both forskolin- and isoproterenol-induced EPSC potentiation was impaired
      in PAG slices of SNL rats. The SNL group had lower AC, but not PDE, activity in
      PAG synaptosomes than the sham group. Conversely, IPSCs in vlPAG slices were not
      different between SNL and sham groups. Intra-vlPAG microinjection of forskolin
      alleviated SNL-induced mechanical allodynia in rats. These results suggest that
      SNL leads to inadequate descending pain inhibition resulting from impaired
      glutamatergic synaptic plasticity mediated by the AC-cAMP-PKA signalling cascade,
      possibly due to AC down-regulation in the PAG, leading to long-term neuropathic
      pain.

PMID- 25868085
TI  - A Facile Strategy for the Construction of Cyclic Peptoids under Microwave
      Irradiation through a Simple Substitution Reaction.
AB  - We describe a fast and efficient side chain-to-tail cyclization of N-substituted
      glycine oligomers, peptoids, on a solid support and under microwave irradiation.
      We demonstrate that cyclic peptoids varied in their ring size and side chains can
      be synthesized by a bond formation between a chloropropyl group placed anywhere
      along the sequence and the secondary amine at the N-terminus. This SN2 reaction
      leads to the formation of a new C-N bond using only one reagent (a base). 

PMID- 25868086
TI  - Irritable bowel syndrome among Japanese adolescents: A nationally representative
      survey.
AB  - BACKGROUND AND AIM: No nationally representative survey of irritable bowel
      syndrome (IBS) among adolescents has ever been performed in Japan. In the present
      study, we aimed to clarify the prevalence of IBS among Japanese adolescents and
      the factors associated with it. METHODS: The items related to the diagnostic
      criteria for IBS based on the Rome III Diagnostic Criteria for Functional
      Gastrointestinal Disorders were included in a cross-sectional nationwide survey
      of "alcohol consumption and smoking habits among junior and senior high school
      students." The participating schools were sampled from among all junior and
      senior high schools in Japan using the cluster-sampling method, and self
      administered questionnaires were sent to the selected schools by mail. Among 99
      416 questionnaires that were collected, data from 98 411 valid responses were
      analyzed. RESULTS: The results showed that the prevalence of IBS was 18.6%.
      Although no sex difference was observed in the overall prevalence of IBS, the
      prevalence of diarrhea-predominant IBS was higher among boys than among girls,
      and the prevalence of constipation-predominant IBS was higher among girls than
      among boys. The prevalence of IBS increased with progression of the school grade,
      and there were the significant relationships between IBS and sleep-phase delay
      and insomnia symptoms. IBS was also significantly associated with poor mental
      health status. CONCLUSION: These results indicate that IBS is common among junior
      and senior high school students, and associated with lifestyle and mental health.

PMID- 25868088
TI  - Earlier, but later than that, though not that early... Simplifying the many
      shades of gray in germ line determination.

PMID- 25868090
TI  - Undue regulatory control on phenobarbital--an important yet overlooked reason for
      the epilepsy treatment gap.

PMID- 25868091
TI  - Letter: Recruitment of patients with both epilepsy and intellectual disability.

PMID- 25868092
TI  - Costs of cervical disc replacement versus anterior cervical discectomy and fusion
      for treatment of single-level cervical disc disease: an analysis of the Blue
      Health Intelligence database for acute and long-term costs and complications.
AB  - STUDY DESIGN: Retrospective review of prospectively collective administrative
      data. OBJECTIVE: The purpose of this study was to determine the reoperation
      rates, adverse event rate, as well as the direct and follow-on costs of cervical
      disc arthroplasty (CDA) compared with anterior cervical discectomy and fusion
      (ACDF) in a "real-world" population of patients with single-level symptomatic
      cervical disc disease. SUMMARY OF BACKGROUND DATA: Until very recently, there was
      a paucity of human clinical data to demonstrate that CDA lowers the rate of
      adjacent segment disease over ACDF. METHODS: This was a retrospective, matched
      cohort analysis of a prospectively collected database of costs and outcomes for
      patients aged 18 to 60 years, who were continuously enrolled in a Blue Cross Plan
      contributing data to a claims database. Inclusion criteria were as follows: all
      patients who were treated surgically with either CDA or ACDF between January 2008
      and December 2009, with single-level cervical pathology and claims reflecting at
      least 6 weeks of nonsurgical preoperative care without claims history of prior
      surgery. RESULTS: There were 6635 ACDF patients and 327 CDA patients. There were
      no significant differences in the incidence of comorbidities or mean follow-up
      time (ACDF 25.7 mo vs. CDA 26.1 mo) between groups. By 36 months postoperatively,
      the reoperation rate was significantly increased in the ACDF group (10.5%) versus
      the CDA group (5.7%) (hazard ratio, P = 0.0214). The index surgery and 90-day
      global window costs were significantly lower in the CDA groups. At final follow
      up, there was a statistically significant reduction in total costs paid by
      insurer in CDA patients (CDA $34,979 vs. ACDF $39,820). CONCLUSION: Patients who
      underwent CDA for single-level degenerative disease had lower readmission rates,
      lower reoperation rates, and reduced index and total costs than those treated
      with ACDF. CDA was effective in reducing the monthly cost of care compared with
      ACDF. LEVEL OF EVIDENCE: 2.

PMID- 25868093
TI  - Spinal injuries in an airplane crash: a description of incidence, morphology, and
      injury mechanism.
AB  - STUDY DESIGN: Retrospective cohort. OBJECTIVE: Spinal injuries of the survivors
      of an airplane crash are described. On the basis of injury morphology and
      knowledge of the conditions of the accident, injury mechanisms are described and
      prevention measures are discussed. SUMMARY OF BACKGROUND DATA: The most common
      causes of spinal fractures are a high energy fall (incidence 21.2%-39%) and motor
      vehicle accidents (21.7%-33.61%). Detailed reports solely on spinal injuries, as
      a result of an airplane crash, are scarce in literature. METHODS: An analysis was
      performed on the spinal injuries of all 126 survivors of a commercial airplane
      (Boeing 737) crash near Amsterdam in 2009. Level of injury and fracture
      classification by morphology, independently performed by 4 specialists in spinal
      trauma, was documented. An analysis was done on the type of injuries and the
      suggested mechanism of injury by evaluating the crash characteristics analysis.
      RESULTS: Twenty-three (18.3%) of the survivors sustained a total of 27 spinal
      injuries. Four (17.1% of the patients with spinal injury) experienced a single
      cervical spine fracture. Eight (29.6%) injuries were at the thoracic spine and 15
      (55.6%) at the lumbar spine level. More than half of the injuries included a
      burst component. CONCLUSION: A high number of spinal injuries was found after
      this airplane crash. The morphology of the injuries consisted of a high rate of
      burst-type fractures presumably caused by a mainly vertical trauma mechanism as
      shown by the accident analysis. LEVEL OF EVIDENCE: 4.

PMID- 25868094
TI  - Characteristics of trunk control during crook-lying unilateral leg raising in
      different types of chronic low back pain patients.
AB  - STUDY DESIGN: Cross-sectional observational study. OBJECTIVE: To quantitatively
      clarify the characteristics of trunk control during unilateral leg-raising
      movement in different types of nonspecific chronic low back pain (NS-CLBP)
      patients who were identified by aggravation of symptoms during trunk movement.
      SUMMARY OF BACKGROUND DATA: Although there is a need to classify NS-CLBP patients
      for clinical decision making in physical therapy, the characteristics of trunk
      control during unilateral leg-raising movement in different types of NS-CLBP
      patients have not been quantitatively analyzed in previous studies by
      simultaneously measuring the lumbar spine movement, trunk muscle activity, and
      leg movement. METHODS: Thirty NS-CLBP patients, of whom 13 were aggravated by
      trunk flexion (flexion group) and 17 were aggravated by trunk extension
      (extension group), and 30 healthy controls performed crook-lying unilateral leg
      raising movement on the painful side in patient group and the dominant leg in
      controls. During the unilateral leg-raising movement, pressure changes produced
      by the movement of the lumbar lordotic curve, measured by a custom-made recording
      device, were used as indices of the lumbar spine movement. Trunk muscle
      activities were recorded by surface electromyography and diagnostic
      ultrasonography. The pressure changes and trunk muscle activities were
      statistically compared among the 3 groups. RESULTS: At foot-off during unilateral
      leg-raising movement, the extension group demonstrated increase in pressure
      changes, whereas the flexion group and controls demonstrated decrease in pressure
      changes. Bilateral external obliques muscle activities in the extension group
      were significantly larger than those in the flexion group and controls (P <
      0.05). CONCLUSION: This study demonstrated that the characteristics of trunk
      control during unilateral leg-raising movement were different depending on the
      types of NS-CLBP patients. These results indicate that patients with NS-CLBP
      might select compensatory trunk control strategies subconsciously to prevent the
      manifestation of LBP. These results also suggest the importance of the different
      characteristics of trunk control during active limb movement in the clinical
      reasoning process for the management of different types of NS-CLBP patients.
      LEVEL OF EVIDENCE: N/A.

PMID- 25868095
TI  - Comparison of Smith-Petersen osteotomy and pedicle subtraction osteotomy for the
      correction of thoracolumbar kyphotic deformity in ankylosing spondylitis: a
      systematic review and meta-analysis.
AB  - STUDY DESIGN: A systematic review and meta-analysis. OBJECTIVE: To compare the
      efficacy and safety outcomes of Smith-Petersen osteotomy (SPO) and pedicle
      subtraction osteotomy (PSO) for patients with ankylosing spondylitis (AS) with
      thoracolumbar kyphotic deformity. SUMMARY OF BACKGROUND DATA: Both SPO and PSO
      are used to correct thoracolumbar kyphotic deformity due to AS. Evidence is
      insufficient to determine which has better efficacy and safety outcomes. METHODS:
      A systematic literature search was performed. Studies concentrating on treating
      thoracolumbar kyphotic deformity due to AS with SPO and/or PSO were included.
      Efficacy was determined with radiographical outcomes, including sagittal vertical
      axis and lumbar lordosis. Safety was determined with complication rates. The data
      were analyzed with Review Manager and R software. RESULTS: Twenty-three studies
      were included. Among them, 5 were comparative studies and were used for a meta
      analysis. All 23 studies were pooled to evaluate the radiographical correction
      and incidence of complications. The meta-analysis of the 5 comparative studies
      showed no significant difference between groups in either correction of sagittal
      vertical axis and lumbar lordosis or incidence of complications. The pooled data
      also showed similar radiological correction and complication rates between SPO
      and PSO. SPO was found to have potential risk of aortic rupture and slightly
      higher risk of permanent neurological deficit without statistical significance,
      whereas PSO was shown longer operative time and more blood loss. CONCLUSION: This
      systematic review and meta-analysis demonstrates that both SPO and PSO are
      effective in correcting thoracolumbar kyphotic deformity in AS and have similar
      risk of most complications. Aortic rupture and related death during correction is
      reported in SPO and should be taken into consideration for decision making. LEVEL
      OF EVIDENCE: 4.

PMID- 25868096
TI  - Re.: Letter to a previous manuscript titled "Detrusor overactivity in patients
      with cauda equina syndrome".

PMID- 25868097
TI  - Re.: Axial gout is frequently associated with the presence of current tophi,
      although not with spinal symptoms.

PMID- 25868098
TI  - Re.: How to make the best use of intraoperative motor evoked potential
      monitoring? Experience in 1162 consecutive spinal deformity surgical procedures.

PMID- 25868099
TI  - Re: How to make the best use of intraoperative motor evoked potential monitoring?
      Experience in 1162 consecutive spinal deformity surgical procedures.

PMID- 25868100
TI  - Antifibrinolytics reduce blood loss in adult spinal deformity surgery: a
      prospective, randomized controlled trial.
AB  - STUDY DESIGN: This is a prospective, randomized, double-blinded comparison of
      tranexamic acid (TXA), epsilon aminocaproic acid (EACA), and placebo used
      intraoperatively in patients with adult spinal deformity. OBJECTIVE: The purpose
      of this study was to provide high-quality evidence regarding the comparative
      efficacies of TXA, EACA, and placebo in reducing blood loss and transfusion
      requirements in patients undergoing posterior spinal fusion surgery. SUMMARY OF
      BACKGROUND DATA: Spine deformity surgery usually involves substantial blood loss.
      The antifibrinolytics TXA and EACA have been shown to improve hemostasis in large
      blood loss surgical procedures. METHODS: Fifty-one patients undergoing posterior
      spinal fusion of at least 5 levels for correction of adult spinal deformity were
      randomized to 1 of 3 treatment groups. Primary outcome measures included
      intraoperative estimated blood loss, total loss, (estimated blood loss +
      postoperative blood loss), and transfusion rates. RESULTS: Patients received TXA
      (n = 19), EACA (n = 19), or placebo (n = 13) in the operating room (mean ages:
      60, 47, and 43 yr, respectively); TXA patients were significantly older and had
      larger estimated blood volumes than both other groups. Total losses were
      significantly reduced for EACA versus control, and there was a demonstrable but
      nonsignificant trend toward reduced intraoperative blood loss in both
      antifibrinolytic arms versus control. EACA had significant reductions in
      postoperative blood transfusions versus TXA. CONCLUSION: The findings in this
      study support the use of antifibrinolytics to reduce blood loss in posterior
      adult spinal deformity surgery. LEVEL OF EVIDENCE: 1.

PMID- 25868101
TI  - Apoptosis in human compressive myelopathy due to metastatic neoplasia.
AB  - STUDY DESIGN: Immunohistochemical assessment of apoptotic markers in human cases
      of compressive myelopathy due to neoplastic compression. OBJECTIVE: To
      characterize the role of apoptosis in neoplastic compressive myelopathy in human
      postmortem tissue with extramedullary tumor involvement. SUMMARY OF BACKGROUND
      DATA: Neoplasms, whether primary or metastatic, may lead to compression of the
      spinal cord and development of a compressive myelopathy syndrome. Apoptotic
      processes of cell death are thought to contribute to cell death in chronic
      compressive myelopathy because of degenerative spondylosis, but this has not
      previously been described in neoplastic compression. METHODS: Six postmortem
      cases of human neoplastic compressive myelopathy were assessed for apoptosis
      using a panel of immunohistochemical markers including Fas, B-cell lymphoma 2
      (Bcl-2), caspase-3 and 9, DNA-dependent protein kinase catalytic subunit (DNA
      PKcs), poly (ADP-ribose) polymerase (PARP), apoptosis-inducing factor (AIF), and
      terminal deoxynucleotide transferase dUTP Nick End Labeling (TUNEL). RESULTS:
      Apoptosis was maximal at the site of tumor compression. Glial cells,
      predominantly oligodendrocytes, were immunopositive for DNA-PKcs, PARP, AIF, and
      TUNEL. Axons were immunopositive for caspase 3, DNA-PKcs, and AIF. Neurons were
      immunopositive for DNA-PKcs, PARP, AIF, and TUNEL. CONCLUSION: The current study
      demonstrates that apoptosis plays a role in human neoplastic compressive
      myelopathy. Necrosis dominates the severe end of the spectrum of compression. The
      prominent oligodendroglial involvement is suggestive that apoptosis may be
      important in the ongoing remodeling of white matter due to sustained compression.
      LEVEL OF EVIDENCE: 4.

PMID- 25868102
TI  - Does location of rotation center in artificial disc affect cervical biomechanics?
AB  - STUDY DESIGN: A 3-dimensional finite element investigation. OBJECTIVE: To compare
      the biomechanical performances of different rotation centers (RCs) in the
      prevalent artificial cervical discs. SUMMARY OF BACKGROUND DATA: Various
      configurations are applied in artificial discs. Design parameters may influence
      the biomechanics of implanted spine. The RC is a primary variation in the popular
      artificial discs. METHODS: Implantation of 5 prostheses was simulated at C5-C6 on
      the basis of a validated finite element cervical model (C3-C7). The prostheses
      included ball-in-socket design with a fixed RC located on the inferior endplate
      (BS-FI) and on the superior endplate (BS-FS), with a mobile RC at the inferior
      endplate (BS-MI), dual articulation with a mobile RC between the endplates (DA
      M), and sliding articulation with various RCs (SA-V). The spinal motions in
      flexion and extension served as a displacement loading at the C3 vertebrae.
      RESULTS: Total disc replacements reduced extension moment. The ball-in-socket
      designs required less flexion moment, whereas the flexion stiffness of the spines
      with DA-M and SA-V was similar to that of the healthy model. The contributions of
      the implanted level to the global motions increased in the total disc
      replacements, except in the SA-V and DA-M models (in flexion). Ball-in-socket
      designs produced severe stress distributions in facet cartilage, whereas DA-M and
      SA-V produced more severe stress distribution on the bone-implant interface.
      CONCLUSION: Cervical stability was extremely affected in extension and partially
      affected in flexion by total disc replacement. With the prostheses with mobile
      RC, cervical curvature was readjusted under a low follower load. The SA-V and BS
      FS designs exhibited better performances in the entire segmental stiffness and in
      the stability of the operative level than the BS-MI and BS-FI designs in flexion.
      The 5 designs demonstrated varying advantages relative to the stress distribution
      in the facet cartilages and on the bone-implant interface. LEVEL OF EVIDENCE: 5.

PMID- 25868103
TI  - Validity of transcranial motor evoked potentials as early indicators of neural
      compromise in rat model of spinal cord compression.
AB  - STUDY DESIGN: Randomized controlled study of intraoperative transcranial motor
      evoked potentials (TcMEPs) as early indicators of neural compromise in a rat
      model of spinal cord compression. OBJECTIVE: To determine the temporal threshold
      at which a complete (100%) loss of intraoperative TcMEPs will result in
      significant postoperative functional deficits. SUMMARY OF BACKGROUND DATA: There
      is controversy about the best TcMEP alarm criteria for intraoperative spinal cord
      protection. Clinical trials provide some evidence, but randomized controlled
      trials, which are not feasible in humans, are lacking. METHODS: Twenty-four adult
      male Wistar rats were divided into 3 experimental groups according to the length
      of time that a 100% TcMEP signal loss was maintained; all animals had
      preoperative functional testing. After surgical placement of a balloon catheter
      in the thoracic sublaminar space, TcMEPs were recorded while the spinal cord was
      compressed by balloon inflation. The recordings were terminated after maintaining
      a 100% TcMEP loss for different time periods (0, 5, or 15 min). Functional
      behavioral testing was repeated after 24 hours. RESULTS: Only the groups wherein
      the catheter was left inflated for 5 or 15 minutes after a complete (100%) loss
      of TcMEP amplitude showed a significant deterioration in functional testing as
      compared with preoperative baseline values. Functional testing remained normal
      for both the control group and the group in which termination of spinal cord
      compression occurred immediately after a decrease of TcMEP amplitude to 100%.
      There was a strong correlation between TcMEP amplitude recovery postintervention
      and functional ability at 24 hours postsurgery. CONCLUSION: If a 100% loss of
      TcMEP signals is immediately recognized and reversed by rapid removal of the
      compressive force on the spinal cord, normal postoperative function was observed
      in this rat model. However, delaying intervention for even 5 minutes can result
      in significant postoperative functional deficits. LEVEL OF EVIDENCE: N/A.

PMID- 25868104
TI  - Establishing the injury severity of thoracolumbar trauma: confirmation of the
      hierarchical structure of the AOSpine Thoracolumbar Spine Injury Classification
      System.
AB  - STUDY DESIGN: Survey of spine surgeons. OBJECTIVE: To develop a validated
      regional and global injury severity scoring system for thoracolumbar trauma.
      SUMMARY OF BACKGROUND DATA: The AOSpine Thoracolumbar Spine Injury Classification
      System was recently published and combines elements of both the Magerl system and
      the Thoracolumbar Injury Classification System; however, the injury severity of
      each fracture has yet to be established. METHODS: A survey was sent to 100
      AOSpine members from all 6 AO regions of the world (North America, South America,
      Europe, Africa, Asia, and the Middle East). Each respondent was asked to
      numerically grade the severity of each variable of the AOSpine Thoracolumbar
      Spine Injury Classification System including the morphology, neurological grade,
      and patient specific modifiers. A grade of zero was considered to be not severe
      at all, and a grade of 100 was the most severe injury possible. RESULTS: Seventy
      four AOSpine surgeons from all 6 AO regions of the world numerically graded the
      severity of each variable of the AOSpine Thoracolumbar Spine Injury
      Classification System to establish the injury severity score. The reported
      fracture severity increased significantly (P < 0.0001) as the subtypes of
      fracture type A and type B increased, and a significant difference (P < 0.0001)
      in severity was established for burst fractures with involvement of 2 versus 1
      endplates. Finally, no regional or experiential difference in severity or
      classification was identified. CONCLUSION: Development of a globally applicable
      injury severity scoring system for thoracolumbar trauma is possible. This study
      demonstrates no regional or experiential difference in perceived severity or
      thoracolumbar spine trauma. The AOSpine Thoracolumbar Spine Injury Classification
      System provides a logical approach to assessing these injuries and enables
      rational strategies for treatment. LEVEL OF EVIDENCE: 4.

PMID- 25868105
TI  - Although inconvenient, baclofen pumps do not complicate scoliosis surgery in
      patients with cerebral palsy.
AB  - STUDY DESIGN: Retrospective review of prospectively collected data. OBJECTIVE: To
      compare patients with operative cerebral palsy with and without an intrathecal
      baclofen pump (ITB) to determine whether an ITB increases the complexity of
      scoliosis surgery and/or increases the risk of wound complications. SUMMARY OF
      BACKGROUND DATA: Options for baclofen pump placement include before, during, or
      after scoliosis surgery. There is some concern that prior placement of an ITB and
      catheter can further complicate cerebral palsy scoliosis surgery and increase the
      risk for wound complications. METHODS: Prospectively collected cases from a
      multicenter cerebral palsy scoliosis database were reviewed for patients who
      underwent posterior spinal instrumentation and fusion for a major coronal
      deformity. These patients were then divided on the basis of whether they had ITB
      at the time of initial scoliosis surgery. The 2 groups were compared to determine
      differences in demographics, operative parameters, radiographical outcomes, and
      rates of wound complications. RESULTS: Of 187 patients identified, 32 had an ITB
      previously placed (ITB group) and 155 did not (non-ITB group). Both groups were
      similar in regard to age, sex, Gross Motor Function Classification Scale score,
      and preoperative Cobb magnitude. When comparing operative parameters, there were
      no differences in the total operating room time (ITB = 375 +/- 127 min, non-ITB =
      423 +/- 178 min; P = 0.149) or total estimated blood loss (ITB = 2323 +/- 1489
      mL, non-ITB = 2081 +/- 1572 mL; P = 0.424). Postoperatively, the 2 groups had
      similar correction rates (71% vs. 67%, P = 0.303). As for perioperative wound
      complications, there were no differences in rates (P = 0.546) between the ITB
      (16%) and non-ITB group (15%). CONCLUSION: Although it may be inconvenient for
      the surgeon, ITBs do not increase the complexity of surgery or the risk for wound
      complications. When counseling patients and their caregivers on the timing of
      pump placement, it does not seem to compromise the care of the patient if the
      baclofen pump is placed first. Further study is needed to evaluate the safety of
      pump placement during or after scoliosis surgery. LEVEL OF EVIDENCE: 4.

PMID- 25868106
TI  - Percutaneous radiofrequency-targeted vertebral augmentation of unstable
      metastatic C2 and C3 lesions using a CT-guided posterolateral approach and ultra
      high-viscosity cement.
AB  - STUDY DESIGN: Case report. OBJECTIVE: To report the first technical note
      describing radio frequency-targeted C2 and C3 vertebral augmentation using a
      posterolateral approach and high-viscosity cement. SUMMARY OF BACKGROUND DATA:
      Percutaneous vertebral augmentation is a minimally invasive procedure used for
      stabilization and pain control in vertebral compression fractures. Its use in the
      cervical spine, especially the upper cervical spine, is very limited mainly due
      to technical challenges. METHODS: We report the first use of an ultra-high
      viscosity cement and posterolateral approach with computed tomography (CT)
      guidance and computed tomographic fluoroscopy in a patient with lytic lesions in
      C2 and C3 and a pathologic fracture of C2 for the purpose of stabilization and
      pain palliation. RESULTS: Technically successful vertebral augmentation of the C2
      and C3 vertebral bodies was achieved. There were no complications. The patient
      reported pain relief and improved range of motion after treatment and the hard
      cervical collar was removed. CONCLUSION: Computed tomography-guided
      radiofrequency-targeted vertebral augmentation of the cervical spine using a
      posterolateral approach and ultra-high-viscosity cement is a technically feasible
      procedure that may be used in patients with advanced osteolytic cervical spine
      metastases who are not surgical candidates for the purpose of pain palliation and
      fracture stabilization. LEVEL OF EVIDENCE: N/A.

PMID- 25868108
TI  - Pediatric teratomas: Still fascinating.

PMID- 25868110
TI  - Water Effect on Acid-Gas Capture Using Choline Lactate: A DFT Insight beyond
      Molecule-Molecule Pair Simulations.
AB  - The suitability of CO2 and SO2 capture by using choline lactate ionic liquid as a
      sorbent and the effect of water content for acid-gas absorption were investigated
      through density functional theory (DFT) simulations in this work. Simulations
      that contain model systems considering up to four molecules (cholinium, lactate,
      water, and CO2/SO2) have been analyzed, and compositional effects on small
      cluster(s) formed by four ionic pairs and variable number of water molecules have
      been studied in this work. Assessment of the effect of water content on acid-gas
      capture that uses exotic ionic liquids is a rare study, and our results showed
      that water presence hinders CO2/SO2 affinity and solubility dramatically, mainly
      due to the dominated affinity between the ionic pair and water molecule rather
      than the CO2/SO2 molecule. Moreover, our studies also showed that affinity
      between ionic liquid and CO2 is hindered by more than ionic liquid and SO2 rich
      system with the presence of water in the environment. 

PMID- 25868109
TI  - Volatility of Mutator Phenotypes at Single Cell Resolution.
AB  - Mutator phenotypes accelerate the evolutionary process of neoplastic
      transformation. Historically, the measurement of mutation rates has relied on
      scoring the occurrence of rare mutations in target genes in large populations of
      cells. Averaging mutation rates over large cell populations assumes that new
      mutations arise at a constant rate during each cell division. If the mutation
      rate is not constant, an expanding mutator population may contain subclones with
      widely divergent rates of evolution. Here, we report mutation rate measurements
      of individual cell divisions of mutator yeast deficient in DNA polymerase epsilon
      proofreading and base-base mismatch repair. Our data are best fit by a model in
      which cells can assume one of two distinct mutator states, with mutation rates
      that differ by an order of magnitude. In error-prone cell divisions, mutations
      occurred on the same chromosome more frequently than expected by chance, often in
      DNA with similar predicted replication timing, consistent with a spatiotemporal
      dimension to the hypermutator state. Mapping of mutations onto predicted
      replicons revealed that mutations were enriched in the first half of the replicon
      as well as near termination zones. Taken together, our findings show that
      individual genome replication events exhibit an unexpected volatility that may
      deepen our understanding of the evolution of mutator-driven malignancies. 

PMID- 25868111
TI  - The validity, reliability and acceptability of the SAVASI; a new self-assessment
      score in vitiligo.
AB  - BACKGROUND: Vitiligo is a common depigmenting skin disorder that can influence a
      patient's quality of life. Although patient-orientated medicine is an emerging
      concept, a self-assessment tool to assess the degree of depigmentation in
      vitiligo is not yet available. Therefore, we developed the SAVASI, a self
      assessment tool that uses the same basic principles as the VASI. OBJECTIVE: To
      assess the validity, reliability and acceptability of the SAVASI. METHODS: To
      assess the validity of the SAVASI, we compared the scores assessed by the patient
      with the scores of the VASI assessed by the physician. To assess the intra-rater
      reliability, the correlation between the baseline SAVASI and the SAVASI after 2
      weeks was calculated. To assess the acceptability, patients indicated the time
      needed to complete the SAVASI and the patient assessed the difficulty of the
      questionnaire on a five-point scale. The Skindex-29 was used to determine the
      quality of life. The overestimation of the SAVASI compared to the VASI was
      calculated by subtracting the VASI scores off from the SAVASI scores. RESULTS: A
      high correlation between the VASI and the SAVASI (ICC 0.97, 95% CI: 0.95-0.98)
      was found in 60 patients. The intra-rater reliability of the SAVASI (ICC 0.75,
      95% CI 0.54-0.87) was adequate in 31 patients. Fifty (83%) of the patients
      completed the questionnaire within 10 min and only five (8%) of the patients
      considered the SAVASI hard. We found no correlation between overestimation of the
      SAVASI score and the Skindex-29 score. CONCLUSION: The SAVASI is a valid,
      reliable and acceptable self-assessment tool to measure the degree of
      depigmentation in vitiligo. With the SAVASI the degree of depigmentation can
      reliably be assessed by the patient themselves which can be useful in large
      (epidemiological) studies. Furthermore, this could contribute to the patient's
      disease insight and therapy loyalty.

PMID- 25868112
TI  - Of matchers and maximizers: How competition shapes choice under risk and
      uncertainty.
AB  - In a world of limited resources, scarcity and rivalry are central challenges for
      decision makers-animals foraging for food, corporations seeking maximal profits,
      and athletes training to win, all strive against others competing for the same
      goals. In this article, we establish the role of competitive pressures for the
      facilitation of optimal decision making in simple sequential binary choice tasks.
      In two experiments, competition was introduced with a computerized opponent whose
      choice behavior reinforced one of two strategies: If the opponent
      probabilistically imitated participant choices, probability matching was optimal;
      if the opponent was indifferent, probability maximizing was optimal. We observed
      accurate asymptotic strategy use in both conditions irrespective of the provision
      of outcome probabilities, suggesting that participants were sensitive to the
      differences in opponent behavior. An analysis of reinforcement learning models
      established that computational conceptualizations of opponent behavior are
      critical to account for the observed divergence in strategy adoption. Our results
      provide a novel appraisal of probability matching and show how this individually
      'irrational' choice phenomenon can be socially adaptive under competition. 

PMID- 25868113
TI  - Post choice information integration as a causal determinant of confidence: Novel
      data and a computational account.
AB  - Confidence judgments are pivotal in the performance of daily tasks and in many
      domains of scientific research including the behavioral sciences, psychology and
      neuroscience. Positive resolution i.e., the positive correlation between choice
      correctness and choice-confidence is a critical property of confidence judgments,
      which justifies their ubiquity. In the current paper, we study the mechanism
      underlying confidence judgments and their resolution by investigating the source
      of the inputs for the confidence-calculation. We focus on the intriguing debate
      between two families of confidence theories. According to single stage theories,
      confidence is based on the same information that underlies the decision (or on
      some other aspect of the decision process), whereas according to dual stage
      theories, confidence is affected by novel information that is collected after the
      decision was made. In three experiments, we support the case for dual stage
      theories by showing that post-choice perceptual availability manipulations exert
      a causal effect on confidence-resolution in the decision followed by confidence
      paradigm. These finding establish the role of RT2, the duration of the post
      choice information-integration stage, as a prime dependent variable that theories
      of confidence should account for. We then present a novel list of robust
      empirical patterns ('hurdles') involving RT2 to guide further theorizing about
      confidence judgments. Finally, we present a unified computational dual stage
      model for choice, confidence and their latencies namely, the collapsing
      confidence boundary model (CCB). According to CCB, a diffusion-process choice is
      followed by a second evidence-integration stage towards a stochastic collapsing
      confidence boundary. Despite its simplicity, CCB clears the entire list of
      hurdles. 

PMID- 25868114
TI  - The role of post-acute care in variation in the Medicare program.

PMID- 25868115
TI  - One-Pot Synthesis of N-Substituted beta-Amino Alcohols from Aldehydes and
      Isocyanides.
AB  - A practical two-stage one-pot synthesis of N-substituted beta-amino alcohols
      using aldehydes and isocyanides as starting materials has been developed. This
      method features mild reaction conditions, broad scope, and general tolerance of
      functional groups. Based on a less common central carbon-carbon bond
      disconnection, this protocol complements traditional approaches that involve
      amines and various carbon electrophiles (epoxides, alpha-halo ketones, beta
      halohydrins). Medicinally relevant products can be prepared in a concise and
      efficient way from simple building blocks, as demonstrated in the synthesis of
      the antiasthma drug salbutamol. Upgrading the synthesis to an enantioselective
      variant is also feasible. 

PMID- 25868116
TI  - Synthesis of a 1,3 beta-glucan hexasaccharide designed to target vaccines to the
      dendritic cell receptor, Dectin-1.
AB  - Transformation of 3-O-benzyl-1,2:5,6-di-O-isopropylidene-alpha-D-glucofuranose
      into 2,4,6-tri-O-benzoyl-3-O-benzyl glucopyranosyl imidate proceeded efficiently
      via crystalline benzyl and per-benzoylated derivatives. This imidate glycosylated
      di-O-isopropylidene-alpha-D-glucofuranose in high yield and glycosylation of the
      disaccharide after removal of the 3'-O-benzyl ether afforded the beta1,3 linked
      trisaccharide in excellent yield. Di- and trisaccharides imidates were readily
      prepared from the furanose terminated glycosylation products but both were
      unreactive in glycosylation reaction with the debenzylated di- and trisaccharide
      alcohols. The 3'-O-benzyl perbenzoylated disaccharide pyranose derivative could
      be selectively debenzoylated and converted to the corresponding perbenzoylated
      4,6:4',6'-di-O-benzylidene derivative. Lewis acid catalyzed glycosidation gave
      the selectively protected disaccharide ethylthioglycoside in good overall yield.
      Glycosidation of this thioglycoside donor with 5-methoxycarbonylpentanol gave the
      disaccharide tether glycoside and after catalytic removal of benzyl ether the
      resulting disaccharide alcohol was glycosylated by the thioglycoside in a 2+2
      reaction to yield a tetrasaccharide. Repetition of selective deprotection of the
      terminal 3-O-benzyl ether followed by glycosylation by the disaccharide
      thioglycoside gave a protected hexasaccharide. Hydrogenolysis of this
      hexasaccharide followed by transesterification and second hydrogenolysis to
      remove a residual benzyl group gave the target hexasaccharide glycoside 1 as a
      Dectin-1 ligand functionalized to permit covalent attachment to glycoconjugate
      vaccines and thereby facilitate improved antigen processing by dendritic cells.

PMID- 25868117
TI  - Theoretical studies on the dissolution of chitosan in 1-butyl-3-methylimidazolium
      acetate ionic liquid.
AB  - In this work, the dissolution mechanism of chitosan in imidazolium acetic-based
      ionic liquid (IL) 1-butyl-3-methylimidazolium acetate was investigated by density
      functional theory (DFT). Chitobiose is considered to symbolize chitosan during
      the DFT calculations. [Bmim]OAc is supposed to be the best suitable IL among the
      investigated ILs for the dissolution of chitosan since the complex formed between
      [Bmim]OAc and chitobiose has the lowest energy. The hydrogen bonds formed by IL
      and chitobiose were studied by discussing the geometric parameter variations and
      the vibration mode analyses. Four strong hydrogen-bond patterns C1-H1 ? O16, C2
      H2 ? O16, O38-H39 ? O1 and O40-H41 ? O2 were found, which means the existence of
      strong interaction between chitosan and [Bmim]OAc. In addition, natural bond
      orbital (NBO) analysis was used to study the second order perturbation
      stabilization energies (E(2)) that denotes the intensity of the interactions
      between chitobiose with H2O and ILs. The E(2) of chitobiose with [Bmim]OAc is
      larger than that of chitobiose with other ILs and solvents studied, which proves
      that chitobiose can be dissolved in [Bmim]OAc but cannot in water and other
      solvents. Atom in molecules (AIM) theory shows that hydrogen bonds between
      chitobiose and [Bmim]OAc are stronger than that between chitobiose and other
      solvents. It means that the interactions between [Bmim]OAc and chitobiose
      interrupt the initial hydrogen bonds in the chitobiose due to the formation of
      new hydrogen bonds in the complexes. The calculation data provide the interaction
      mechanism of the dissolution of chitosan in [Bmim]OAc.

PMID- 25868118
TI  - Glutamate and hypoxia as a stress model for the isolated perfused vertebrate
      retina.
AB  - Neuroprotection has been a strong field of investigation in ophthalmological
      research in the past decades and affects diseases such as glaucoma, retinal
      vascular occlusion, retinal detachment, and diabetic retinopathy. It was the
      object of this study to introduce a standardized stress model for future
      preclinical therapeutic testing. Bovine retinas were prepared and perfused with
      an oxygen saturated standard solution, and the ERG was recorded. After recording
      stable b-waves, hypoxia (pure N2) or glutamate stress (250 um glutamate) was
      exerted for 45 min. To investigate the effects on photoreceptor function alone, 1
      mM aspartate was added to obtain a-waves. ERG-recovery was monitored for 75 min.
      For hypoxia, a decrease in a-wave amplitude of 87.0% was noted (p<0.01) after an
      exposition time of 45 min (decrease of 36.5% after the end of the washout
      p=0.03). Additionally, an initial decrease in b-wave amplitudes of 87.23% was
      recorded, that reached statistical significance (p<0.01, decrease of 25.5% at the
      end of the washout, p=0.03). For 250 um glutamate, an initial 7.8% reduction of a
      wave amplitudes (p>0.05) followed by a reduction of 1.9% (p>0.05). A reduction of
      83.7% of b-wave amplitudes (p<0.01) was noted; after a washout of 75 min the
      reduction was 2.3% (p=0.62). In this study, a standardized stress model is
      presented that may be useful to identify possible neuroprotective effects in the
      future.

PMID- 25868119
TI  - Attitudes Toward Risk and Informed Consent for Research on Medical Practices: A
      Cross-sectional Survey.
AB  - BACKGROUND: The U.S. Office for Human Research Protections has proposed that end
      points of randomized trials comparing the effectiveness of standard medical
      practices are risks of research that would require disclosure and written
      informed consent, but data are lacking on the views of potential participants.
      OBJECTIVE: To assess attitudes of U.S. adults about risks and preferences for
      notification and consent for research on medical practices. DESIGN: Cross
      sectional survey conducted in August 2014. SETTING: Web-based questionnaire.
      PATIENTS: 1095 U.S. adults sampled from an online panel (n = 805) and an online
      convenience river sample (n = 290). MEASUREMENTS: Attitudes toward risk, informed
      consent, and willingness to participate in 3 research scenarios involving medical
      record review and randomization of usual medical practices. RESULTS: 97% of
      respondents agreed that health systems should evaluate standard treatments. Most
      wanted to be asked for permission to participate in each of 3 scenarios (range,
      75.2% to 80.4%), even if it involved only medical record review, but most would
      accept nonwritten (oral) permission or general notification if obtaining written
      permission would make the research too difficult to conduct (range, 70.2% to
      82.7%). Most perceived additional risk from each scenario (range, 64.0% to
      81.6%). LIMITATION: Use of hypothetical scenarios and a nonprobability sample
      that was not fully representative of the U.S. population. CONCLUSION: Most
      respondents preferred to be asked for permission to participate in observational
      and randomized research evaluating usual medical practices, but they are willing
      to accept less elaborate approaches than written consent if research would
      otherwise be impracticable. These attitudes are not aligned with proposed
      regulatory guidance. PRIMARY FUNDING SOURCE: National Center for Advancing
      Translational Sciences at the National Institutes of Health.

PMID- 25868120
TI  - Figure correction: Designing messaging to engage patients in an online suicide
      prevention intervention: survey results from patients with current suicidal
      ideation.

PMID- 25868121
TI  - The Influence of the CYP3A4*22 Polymorphism and CYP2D6 Polymorphisms on Serum
      Concentrations of Aripiprazole, Haloperidol, Pimozide, and Risperidone in
      Psychiatric Patients.
AB  - INTRODUCTION: Cytochrome P450 3A4 (CYP3A4) is involved in the metabolism of
      greater than 50% of the prescribed drugs. Recently, the CYP3A4*22 allele was
      reported to be associated with lower CYP3A4 expression and activity. Quetiapine,
      an antipsychotic metabolized by only CYP3A4, displayed higher serum levels in
      CYP3A4*22 carriers. Aripiprazole, haloperidol, pimozide, and risperidone are
      antipsychotics that are metabolized by CYP3A4 and CYP2D6. We investigated to
      which degree the CYP3A4*22 single-nucleotide polymorphism affects serum
      concentrations of patients receiving these drugs and compared this with the
      influence of CYP2D6 polymorphisms. METHODS: Eight hundred thirty-four adult
      patients were included in this study, of whom 130 used aripiprazole, 312 used
      haloperidol, 86 used pimozide, and 396 used risperidone. Serum levels of the drug
      and, if available, their active metabolites were collected as well as information
      on dose. Patients were genotyped for CYP3A4*22 using restriction fragment length
      polymorphism analysis. Genotyping for CYP2D6 was done with allele-specific
      polymerase chain reaction. RESULTS: No differences were found in serum (dose
      corrected) concentrations of the antipsychotics between CYP3A4*22 wild-type and
      carrier groups. In contrast, CYP2D6 genotype did affect dose-corrected
      concentrations of the antipsychotics: for example, median dose-corrected
      concentrations were 56%, 86%, and 400% higher in predicted poor metabolizers
      versus extensive metabolizers for aripiprazole (P = 0.004), haloperidol (P >
      0.001), and risperidone (P < 0.001), respectively, although a multiple regression
      analysis showed that only 4% to 17% of the variation in these concentrations
      could be explained by CYP2D6 status. CONCLUSIONS: Heterozygous presence of
      CYP3A4*22 does not increase serum levels of antipsychotics metabolized by both
      CYP3A4 and CYP2D6, whereas CYP2D6 polymorphisms do affect serum levels to a
      limited extent.

PMID- 25868122
TI  - Building Trust: The History and Ongoing Relationships Amongst DSD Clinicians,
      Researchers, and Patient Advocacy Groups.
AB  - Individuals born with differences or disorders of sex development (DSD) have been
      marginalized by society and the health care system. Standards of care in the mid
      20(th) century were based on fixing the child with a DSD, using hormonal and
      surgical interventions; these treatments and the diagnoses were almost never
      disclosed to the child, and sometimes they were not disclosed to the parents.
      This led to secrecy, shame, and stigma. When these children became adults and
      demanded access to their medical records, the realization of the depth of secrecy
      led to the formation of activism groups that shook the medical community. Despite
      precarious beginnings, advocates, health care professionals, and researchers were
      able to elicit changes in the standard of care. The 2006 Consensus Statement on
      Management of Intersex Disorders called for a multidisciplinary approach to care
      and questioned the evidence for many of the standard procedures. Standard of care
      moved from a concealment model to a patient-centered paradigm, and funding
      agencies put resources into determining the future paths of research on DSD.
      Recognition of the need to address patient priorities led to changing
      international standards for including patients in research design. Some
      challenges that remain include: the findings from the Institute of Medicine that
      sexual and gender minorities experience poor health outcomes; establishing trust
      across all parties; developing a common language and creating venues where
      individuals can participate in dialogue that addresses personal experiences,
      research design, clinical practices and intervention strategies. 

PMID- 25868123
TI  - Helicobacter pylori Infection in Early Childhood and Growth at School Age.
AB  - BACKGROUND: There are conflicting results regarding the role of H. pylori in
      children's growth. We examined differences in growth indices at school age
      according to H. pylori infection acquisition in preschool age. MATERIALS AND
      METHODS: A prospective study was undertaken between 2004 and 2009, in which of
      healthy children (N = 139, ages 3-5 years at baseline) were tested for the
      presence of H. pylori antigen in their stool using enzyme-linked immunoassay and
      followed-up till age 6-9 years (median follow-up time 45 months). Height, weight,
      and hemoglobin levels were measured, and socioeconomic data were obtained. Z
      scores of height for age, weight for age, and body mass index for age at baseline
      and follow-up were calculated using the 2000 Center for Disease Control and
      Prevention growth reference curves. Growth velocity (cm/month) between preschool
      and school age was compared between H. pylori-infected and uninfected children
      using mixed models. RESULTS: Fifty-three percent of the children were H. pylori
      positive at baseline, and all except one child tested positive at follow-up. The
      adjusted mean Z score of height for age at follow-up was significantly lower
      among H. pylori-infected children than uninfected ones: 0.15 (95% confidence
      intervals (CIs) 0.02, 0.29) and 0.45 (95% CI 0.29, 0.60), respectively (p =
      .002). Growth velocity was slower in the former group -0.0264 cm/month (95% CI 
      0.047, -0.005) (p = .014), after adjusting for baseline height and age. H. pylori
      infection was not associated with body weight. CONCLUSIONS: Helicobacter pylori
      infection acquired in early childhood may have long-term adverse influence on
      linear growth at school age.

PMID- 25868124
TI  - Characterization of in vitro antifungal activities of small and American
      cranberry (Vaccinium oxycoccos L. and V. macrocarpon Aiton) and lingonberry
      (Vaccinium vitis-idaea L.) concentrates in sugar reduced fruit spreads.
AB  - In this study, cranberry and lingonberry concentrates were added to commercial
      sugar-reduced fruit spreads (raspberry-Aloe vera, strawberry-guava, and
      strawberry-lime), and tested for their antifungal activities. Selected strains of
      the species Absidia glauca, Penicillium brevicompactum, Saccharomyces cerevisiae
      and Zygosaccharomyces bailii, as well as xerophilic environmental isolates of the
      genera Penicillium and Eurotium were used for challenge testing. Initially,
      varying concentrations of synthetic antifungal agents, such as sodium benzoate,
      potassium sorbate and butyl 4-hydroxybenzoate were tested against these fungi on
      wort agar containing 31% fructose at different pH values. Subsequently, the
      experiments were conducted in fruit spreads containing different concentrations
      of cranberry and lingonberry concentrates. The results of this study demonstrate
      that these concentrates were able to inhibit growth of visible colonies of
      xerophilic and non-xerophilic fungi. Cranberry and lingonberry concentrates are
      interesting candidates for natural preservation against fungal growth in sugar
      reduced fruit spreads. 

PMID- 25868125
TI  - Chromosomal damage and micronucleus induction by MP-124, a novel poly(ADP-ribose)
      polymerase-1 (PARP-1) inhibitor: Evidence for a non-DNA-reactive mode of action.
AB  - MP-124, a novel poly(ADP-ribose) polymerase-1 (PARP-1) inhibitor that competes
      with the binding of the PARP substrate nicotinamide adenine dinucleotide (NAD),
      is being developed as a neuroprotective agent against acute ischemic stroke. MP
      124 increased structural chromosomal aberration in CHL/IU cells, but showed
      negative results in the bacterial reverse mutation test, and the rat bone marrow
      micronucleus (MN) and the rat liver unscheduled DNA synthesis tests after the
      intravenous bolus injection. Thus, MP-124 did not appear to be direct-acting
      mutagen. Since, PARP-1 is a key enzyme in DNA repair, the effect of continuous
      PARP-1 inhibition by MP-124 was further examined in the rat MN test under 24-h
      intravenous infusion, and an increase in micronucleated immature erythrocytes
      (MNIE) was observed. The increase was clearly reduced by co-treatment with
      nicotinic acid, which resulted in increased intracellular NAD levels. This is
      consistent with the established activity of MP-124 as a competitive inhibitor of
      PARP and provides strong evidence that the DNA-damaging effect that leads to the
      increase in MNIE is a secondary effect of PARP-1 inhibition. This mechanism is
      expected to result in a threshold for the induction of MNIE by MP-124, and allows
      for the establishment of a safe margin of exposure for the therapeutic use of MP
      124. 

PMID- 25868126
TI  - The mutagenic assessment of mainstream cigarette smoke using the Ames assay: a
      multi-strain approach.
AB  - Salmonella typhimurium strains TA1535, TA1537, TA97, TA102 and TA104 were
      assessed for their suitability and use in conjunction with a Vitrocell((r)) VC 10
      Smoking Robot and 3R4F reference mainstream cigarette smoke. Little information
      exists on TA97, TA104, TA1535, TA1537 and TA102 using an aerosol 35mm spread
      plate format. In this study, TA1535 and TA1537 were considered sub-optimal for
      use with a scaled-down format, due to low spontaneous revertant numbers (0-5
      revertants/plate). In the context of a regulatory environment, TA97 is deemed an
      acceptable alternative for TA1537 and was therefore selected for whole smoke
      exposure in this study. However, there is no acceptable alternative for TA1535,
      therefore this strain was included for whole smoke exposure. TA1535, TA97, TA102
      and TA104 were assessed for mutagenic responses following exposure to cigarette
      smoke at varying concentrations (using diluting airflow rates of 1.0, 4.0, 8.0
      and 12.0L/min), and exposure times of 24 and 64min. A positive mutagenic response
      to cigarette smoke was observed in strain TA104 at both the 24 and 64min time
      points, in the presence of S-9, at the highest smoke concentration tested
      (1.0L/min diluting airflow). The three remaining strains were found to be
      unresponsive to cigarette smoke at all concentrations tested, in the presence and
      absence of metabolic activation. Cigarette smoke particulate deposition was
      quantified in situ of exposure using quartz crystal microbalance technology,
      enabling data to be presented against an associated gravimetric mass (MUg/cm(2)).
      Finally, data obtained in this study were combined with previously published Ames
      data for TA98, TA100, YG1024, YG1042 and Escherichia coli (WP2 uvrA pKM101),
      generated using the same 35mm methodology. The combined data-set was used to
      propose an aerosol testing strategy, based on strain compatibility with the whole
      smoke aerosol, whilst maintaining the essence of the regulatory guidelines for
      the standard Ames assay. 

PMID- 25868127
TI  - Assessment of a twice dosing regimen both before and after partial hepatectomy in
      the rat liver micronucleus test.
AB  - The liver micronucleus test is an important method to detect in vivo
      genotoxicants, especially those that require metabolic activation for their
      genotoxicity. We have already reported that structural or numerical chromosome
      aberration inducers have to be given before or after partial hepatectomy,
      respectively, to detect their genotoxicity in the liver of rats. In the present
      study, we assessed a twice dosing regimen, in which the genotoxicant is dosed
      both before and after partial hepatectomy, using the four chromosome aberration
      inducers used in the previous study. Two structural chromosome aberration
      inducers (diethylnitrosamine and 1,2-dimethylhydrazine) and two numerical
      chromosome aberration inducers (colchicine and carbendazim) were used. The
      genotoxicant was administered to 8-week old male F344 rats one day before and
      again one day after the partial hepatectomy and hepatocytes were isolated 3 days
      after second dosing (4 days after the partial hepatectomy). As a result, all
      genotoxicants (structural or numerical chromosome aberration inducers) caused a
      dose-dependent statistically significant increase in the incidence of
      micronucleated hepatocytes when given both before and after partial hepatectomy.
      No marked difference was observed in general toxicity, relative liver weight and
      cell classification between single dosing regimens and twice dosing regimen of
      the genotoxicants. These results confirm that the twice dosing regimen, in which
      the test compound is dosed both before and after partial hepatectomy, can detect
      in vivo induction of micronucleated hepatocytes by structural or numerical
      chromosome aberration inducers qualitatively similar to their appropriate regimen
      in which the test compound is administered either before or after partial
      hepatectomy. 

PMID- 25868128
TI  - Induction of Pig-a mutant erythrocytes in male and female rats exposed to 1,3
      propane sultone, ethyl carbamate, or thiotepa.
AB  - Validation of the Pig-a gene mutation assay has been based mainly on studies in
      male rodents. To determine if the mutagen-induced responses of the X-linked Pig-a
      gene differ in females compared to males, groups of five male and female Sprague
      Dawley rats were exposed to the mutagens 1,3-propane sultone (80mg/kg/day), ethyl
      carbamate (600mg/kg/day), or thiotepa (7.5mg/kg/day) for three consecutive days
      (study days 1-3). Pig-a mutant phenotype reticulocyte (RET(CD59-)) and mutant
      phenotype erythrocyte (RBC(CD59-)) frequencies were determined on study days -4,
      15, 30 and 46 using immunomagnetic separation in conjunction with flow cytometric
      analysis (In Vivo MutaFlow((r))). While the percentage of reticulocytes (%RET)
      was markedly higher for pre-treatment blood samples from males compared to
      females (6.6% vs. 3.5%), this sex effect was slight or nonexistent at later time
      points. Treatment-related effects to %RET were generally modest owing to the 12
      day interval between last exposure and blood sampling. Mean RET(CD59-) and
      RBC(CD59-) frequencies were consistently low in vehicle control animals of both
      sexes, with 77% of samples exhibiting mutant cell frequencies <=1*10(-6) over
      study days 15-46. Treatment with each mutagen caused significant increases to
      mean RET(CD59-) and RBC(CD59-) frequencies. Whereas genotoxicant-induced RET(CD59
      ) values were maximal on day 15, induced RBC(CD59-) frequencies were highest at
      the last sampling time. Sex did not affect 1,3-propane sultone- or thiotepa
      induced mutant cell frequencies. While ethyl carbamate-exposed females exhibited
      higher mean mutant cell frequencies compared to like-treated males, statistical
      significance was achieved only for RBC(CD59-) at one time point (7.6+/-1.0*10(-6)
      compared to 4.7+/-0.6*10(-6) on day 30). Thus, while some quantitative
      differences were evident, there were no qualitative differences in how males and
      females responded to three diverse mutagens. These data support the use of both
      sexes for Pig-a gene mutation studies. 

PMID- 25868129
TI  - DNA damage is increased in lymphocytes of patients with metabolic syndrome.
AB  - We assessed DNA damage in patients with metabolic syndrome (MetS) by performing
      comet and micronucleus (MN) assays on peripheral blood lymphocyte cultures from
      study participants. 52 MetS patients and 35 age-matched healthy controls were
      evaluated for abdominal obesity, body-mass index (BMI), blood pressure, serum
      triglycerides, HbA1c, HDL-C, and fasting blood glucose levels. In addition,
      malondialdehyde (MDA) levels and activities of superoxide dismutase (SOD) and
      glutathione peroxidase (GSH-Px) were determined. Serum levels of triglycerides,
      HbA1c, fasting blood glucose and waist circumference, systolic blood pressure,
      diastolic blood pressure, and BMI of the subjects in the MetS group were
      significantly higher than those of the control group (for each, p<0.001).
      However, the mean level of HDL-C in the MetS group was lower than in the control
      group (p<0.001). In the study, the length of comet tails was significantly higher
      in the MetS patients (10.23+/-1.98, range 5.72-15.08) than in the controls
      (3.12+/-1.73, range 0.6-7.1) (p<0.001). MN frequency was also significantly
      increased in MetS patients (3.68+/-1.27 per 1000 cells) compared to that of the
      control group (1.81+/-0.84 per 1000 cells) (p<0.001). Micronucleated cell
      frequency and comet-tail length in subjects showed positive correlations with
      waist circumference, BMI, and plasma triglyceride levels (p<0.01) and negative
      correlations with HDL-C levels (p<0.01). Among the oxidative stress factors, MDA
      levels were significantly higher in MetS patients than in the controls. However,
      SOD and GSH-Px enzyme activities were significantly lower in the MetS group than
      in the controls. These findings suggest that patients with MetS have increased
      DNA damage and oxidative stress. 

PMID- 25868130
TI  - Micronucleated erythrocytes in newborns of rat dams exposed to ultraviolet-A
      light during pregnancy; protection by ascorbic acid supplementation.
AB  - Pregnant hairless rat dams were exposed to ultraviolet-A light (UVA) to induce
      micronucleated erythrocytes (MNE) in their fetuses. The control group was exposed
      to conventional light; the experimental groups were exposed to UVA (365nm) during
      gestational days 16-21. In some cases, ascorbic acid (Asc) was administered in
      the drinking water from gestational day 15 until delivery. Dams were sampled at
      48-h intervals during gestation, from day 16 until delivery. Blood was also
      obtained from neonates at birth; MNE, micronucleated polychromatic erythrocytes
      (MNPCE), and polychromatic erythrocytes (PCE) were scored. Increased MNE and
      MNPCE were observed in neonates born to mothers exposed to UVA for 40, 80 or
      160min, compared to the control group. Asc treatment reduced MNE and MNPCE
      induction. 

PMID- 25868131
TI  - Increased oxidative stress in AOA3 cells disturbs ATM-dependent DNA damage
      responses.
AB  - Ataxia telangiectasia (AT) is caused by a mutation in the ataxia-telangiectasia
      mutated (ATM) gene; the condition is associated with hyper-radiosensitivity,
      abnormal cell-cycle checkpoints, and genomic instability. AT patients also show
      cerebellar ataxia, possibly due to reactive oxygen species (ROS) sensitivity in
      neural cells. The ATM protein is a key regulator of the DNA damage response.
      Recently, several AT-like disorders have been reported. The genes responsible for
      them are predicted to encode proteins that interact with ATM in the DNA-damage
      response. Ataxia with oculomotor apraxia types 1-3 (AOA1, 2, and 3) result in a
      neurodegenerative and cellular phenotype similar to AT; however, the basis of
      this phenotypic similarity is unclear. Here, we show that the cells of AOA3
      patients display aberrant ATM-dependent phosphorylation and apoptosis following
      gamma-irradiation. The ATM-dependent response to H2O2 treatment was abrogated in
      AOA3 cells. Furthermore, AOA3 cells had reduced ATM activity. Our results suggest
      that the attenuated ATM-related response is caused by an increase in endogenous
      ROS in AOA3 cells. Pretreatment of cells with pyocyanin, which induces endogenous
      ROS production, abolished the ATM-dependent response. Moreover, AOA3 cells had
      decreased homologous recombination (HR) activity, and pyocyanin pretreatment
      reduced HR activity in HeLa cells. These results indicate that excess endogenous
      ROS represses the ATM-dependent cellular response and HR repair in AOA3 cells.
      Since the ATM-dependent cell-cycle checkpoint is an important block to
      carcinogenesis, such inactivation of ATM may lead to tumorigenesis as well as
      neurodegeneration. 

PMID- 25868132
TI  - Analysis of dibenzo[def,p]chrysene-deoxyadenosine adducts in wild-type and
      cytochrome P450 1b1 knockout mice using stable-isotope dilution UHPLC-MS/MS.
AB  - The polycyclic aromatic hydrocarbon (PAH), dibenzo[def,p]chrysene (DBC; also
      known as dibenzo[a,l]pyrene), is a potent carcinogen in animal models and a class
      2A human carcinogen. Recent investigations into DBC-mediated toxicity identified
      DBC as a potent immunosuppressive agent similar to the well-studied
      immunotoxicant 7,12-dimethylbenz[a]anthracene (DMBA). DBC, like DMBA, is
      bioactivated by cytochrome P450 (CYP) 1B1 and forms the reactive metabolite DBC
      11,12-diol-13,14-epoxide (DBCDE). DBCDE is largely responsible for the
      genotoxicity associated with DBC exposure. The immunosuppressive properties of
      several PAHs are also linked to genotoxic mechanisms. Therefore, this study was
      designed to identify DBCDE-DNA adduct formation in the spleen and thymus of wild
      type and cytochrome P450 1b1 (Cyp1b1) knockout (KO) mice using a highly sensitive
      stable-isotope dilution UHPLC-MS/MS method. Stable-isotope dilution UHPLC-MS/MS
      identified the major DBC adducts (+/-)-anti-cis-DBCDE-dA and (+/-)-anti-trans
      DBCDE-dA in the lung, liver, and spleen of both WT and Cyp1b1 KO mice. However,
      adduct formation in the thymus was below the level of quantitation for our
      method. Additionally, adduct formation in Cyp1b1 KO mice was significantly
      reduced compared to wild-type (WT) mice receiving DBC via oral gavage. In
      conclusion, the current study identifies for the first time DBCDE-dA adducts in
      the spleen of mice supporting the link between genotoxicity and
      immunosuppression, in addition to supporting previous studies identifying Cyp1b1
      as the primary CYP involved in DBC bioactivation to DBCDE. The high levels of DBC
      DNA adducts identified in the spleen, along with the known high levels of Cyp1b1
      expression in this organ, supports further investigation into DBC-mediated
      immunotoxicity. 

PMID- 25868134
TI  - Do women need screening for extragenital gonococcal and chlamydial infections?

PMID- 25868133
TI  - Neisseria gonorrhoeae and Chlamydia trachomatis among women reporting
      extragenital exposures.
AB  - BACKGROUND: The Centers for Disease Control and Prevention recommends pharyngeal
      screening of Neisseria gonorrhoeae (GC) and rectal screening of GC and Chlamydia
      trachomatis (CT) in HIV-infected and at-risk men who have sex with men (MSM).
      There are currently no recommendations to routinely screen women at extragenital
      sites. We define the prevalence of extragenital GC and CT in women attending 2
      urban sexually transmitted disease clinics in Baltimore City and compare it with
      the prevalence of extragenital infections in MSM and men who have sex with women.
      METHODS: All patients who reported extragenital exposures in the preceding 3
      months, who presented for care between June 1, 2011, and May 31, 2013, and who
      were tested for GC and CT using nucleic acid amplification tests at all sites of
      exposure were included in the analyses. We used logistic regression models to
      identify risk factors for extragenital infections. RESULTS: A total of 10,389
      patients were included in this analysis (88% African American; mean age, 29
      years; 42% women; 7% MSM; 2.5% HIV infected). The prevalence estimates of any
      extragenital GC and CT were as follows: 2.4% GC and 3.7% CT in women, 2.6% GC and
      1.6% CT in men who have sex with women, and 18.9% GC and 11.8% CT in MSM. Among
      women, 30.3% of GC infections and 13.8% of CT infections would have been missed
      with urogenital-only testing. Unlike MSM, age <= 18 years was the strongest
      predictor of extragenital infections in women. CONCLUSIONS: Although the
      prevalence of extragenital gonorrhea and chlamydia is highest in MSM, a
      significant number of GC and CT infections in young women would be missed with
      genital-only testing. Cost-effectiveness analyses are needed to help inform
      national guidelines on extragenital screening in young women.

PMID- 25868135
TI  - Evaluation of a new website design for iwantthekit for chlamydia, gonorrhea, and
      trichomonas screening.
AB  - The www.iwantthekit.org provides Internet-based, at-home sexually transmitted
      infection screening. The Web site implemented an automated test result access
      system. To evaluate potential deleterious effects of the new system, we analyzed
      demographics, Web site usage, and treatment. The post-Web site design captured
      more participant information and no decrease in requests, kit return, or
      treatment adherence. 

PMID- 25868136
TI  - Behavioral, immunologic, and virologic correlates of oral human papillomavirus
      infection in HIV-infected youth.
AB  - BACKGROUND: Little is known about the epidemiology or risk factors for oral human
      papillomavirus (HPV) in HIV-infected youth. The objectives of this study were to
      determine the prevalence and correlates of oral HPV infection and to explore the
      association between HPV vaccination and oral infection in HIV-infected youth.
      METHODS: Youth 12 to 24 years of age with behaviorally acquired HIV were
      recruited for this cross-sectional study. Procedures involved medical chart
      review, survey, and collection of an oral rinse sample. Univariable and
      multivariable logistic regression models were used to determine whether
      demographic, behavioral, immunologic, and virologic factors and history of
      vaccination were significantly associated with oral HPV infection. RESULTS: Mean
      age of the 272 participants was 21.5 years; 64% were non-Hispanic black and 20.2%
      were Hispanic; and 10.8% of men compared with 20.3% of women were fully
      vaccinated. Human papillomavirus prevalence was 19.7% in men and 18.6% in women
      (P = 1.0). Only men were positive for vaccine-type HPV: 5.6% were positive for
      HPV-6, HPV-11, HPV-16, and/or HPV-18, and 4.2% were positive for HPV-16 and/or
      HPV-18. Among men who were fully vaccinated, none were positive for HPV-6, HPV
      11, HPV-16, and/or HPV-18, compared with 12 (6.3%) of men who were not fully
      vaccinated (P = 0.37). Two variables were marginally associated with oral HPV (P
      < 0.10): marijuana use in the previous 3 months and lower CD4+ T-cell count.
      CONCLUSIONS: Prevalence rates of oral HPV were relatively high in this population
      of HIV-infected youth and were similar in male and female youth. No fully
      vaccinated men were infected with vaccine-type HPV.

PMID- 25868137
TI  - Seroprevalence and seroincidence of herpes simplex virus (2006-2010), syphilis
      (2006-2010), and vaccine-preventable human papillomavirus subtypes (2000-2010)
      among US military personnel.
AB  - BACKGROUND: Sexually transmitted infections have historically been burdensome in
      military populations. We describe the seroprevalence and seroincidence of vaccine
      preventable human papillomavirus (VP-HPV) subtypes in a sample of 200 servicemen,
      along with the seroprevalence and seroincidence of herpes simplex virus (HSV-1/2)
      and syphilis in a sample of 200 men and 200 women. METHODS: Sera from 200 men,
      along with associated demographic data, were obtained and tested for HPV
      serotypes at service entry and 10 years later. Similarly, 200 active-duty men and
      200 active-duty women were tested for HSV-1/2 at entry to service and 4 years
      later. RESULTS: The baseline prevalence of VP-HPV subtypes was 14.5%, and
      cumulative seroincidence of new infection was 34% over a 10-year period (n = 68).
      Of these, 63% (n = 43) represented HPV-6, HPV-11, or both; 18% of new infections
      were either HPV-16 or HPV-18, and 19% (n = 13) were a mixture of all 4 strains.
      At entry to military service, 33.5% of men were seropositive for HSV-1 and 1.5%
      were positive for HSV-2; seroincidence was 3.4 and 1.1 per 100 person-years,
      respectively. Among women, 39% were seropositive for HSV-1 and 4.0% for HSV-2;
      seroincidence was 5.5 and 3.3 per 100 person-years, respectively. There were 2
      prevalent and 3 incident cases of syphilis. CONCLUSIONS: Sexually transmitted
      infections in military populations are highly prevalent, incident, and
      epidemiologically distinct. Our data show the rates of HPV and HSV-1/2
      acquisition that are higher than those seen in the general public, again
      highlighting the need for continued preventive efforts. Consideration of
      universal HPV vaccination among men is warranted.

PMID- 25868138
TI  - Relationship between community-level alcohol outlet accessibility and individual
      level herpes simplex virus type 2 infection among young women in South Africa.
AB  - BACKGROUND: Exposure to alcohol outlets may influence sexual health outcomes at
      the individual and community levels. Visiting alcohol outlets facilitates alcohol
      consumption and exposes patrons to a risky environment and network of potential
      partners, whereas the presence of alcohol outlets in the community may shift
      social acceptance of riskier behavior. We hypothesize that living in communities
      with more alcohol outlets is associated with increased sexual risk. METHODS: We
      performed a cross-sectional analysis in a sample of 2174 South African
      schoolgirls (ages 13-21 years) living across 24 villages in the rural Agincourt
      subdistrict, underpinned by long-term health and sociodemographic surveillance.
      To examine the association between number of alcohol outlets in village of
      residence and individual-level prevalent herpes simplex virus type 2 (HSV-2)
      infection, we used generalized estimating equations with logit links, adjusting
      for individual- and village-level covariates. RESULTS: The median number of
      alcohol outlets per village was 3 (range, 0-7). Herpes simplex virus type 2
      prevalence increased from villages with no outlets (1.4% [95% confidence
      interval, 0.2-12.1]), to villages with 1 to 4 outlets (4.5% [3.7-5.5]), and to
      villages with more than 4 outlets (6.3% [5.6, 7.1]). An increase of 1 alcohol
      outlet per village was associated with an 11% increase in the odds of HSV-2
      infection (adjusted odds ratio [95% confidence interval], 1.11 [0.98-1.25]).
      CONCLUSIONS: Living in villages with more alcohol outlets was associated with
      increased prevalence of HSV-2 infection in young women. Structural interventions
      and sexual health screenings targeting villages with extensive alcohol outlet
      environments could help prevent the spread of sexually transmitted infections.

PMID- 25868139
TI  - It is complicated: sexual partner characteristic profiles and sexually
      transmitted infection rates within a predominantly African American population in
      Mississippi.
AB  - BACKGROUND: Mississippi has among the highest prevalence of sexually transmitted
      infections (STIs) in the United States. Understanding sexual networks can provide
      insight into risk factors for transmission and guide prevention interventions.
      METHODS: Participants included 1437 primarily African American (95%) adults
      presenting for care at an STI clinic in Jackson, Mississippi. Latent class
      analysis identified underlying population subgroups with unique patterns of
      response on a comprehensive set of 14 sexual partner variables, such as living
      with or having a child with a partner, partner dependence and trust, 1-time
      sexual encounters, multiple main partners, substance use, sexual concurrency, and
      incarceration. Classes were compared on participant age, sex, sexual orientation,
      public assistance, lifetime partners, relationship status, and self-reported past
      year STI. RESULTS: Three classes emerged. Class 1 (n = 746) participants were
      less dependent on partners and less likely to live with or have a child with a
      partner. Class 2 participants (n = 427) endorsed multiple STI risk factors,
      including partner incarceration, 6 or more lifetime partners, sexual concurrency,
      1-time sexual encounters, and substance use at last sex. Class 3 participants (n
      = 226) were more likely to be in dependent, committed relationships with
      children. Class 2 had a higher proportion of self-report past-year STIs (36.7%)
      compared with classes 1 (26.6%) and 3 (26.1%). CONCLUSIONS: Certain partner
      factors such as incarceration, substance use, and concurrency may contribute to
      increased STI risk. Partner factors may be useful proxies for STI risks and could
      be useful questions to include in screening questionnaires in clinical settings.

PMID- 25868140
TI  - Incidence, persistence, and determinants of human papillomavirus infection in a
      population of Inuit women in northern Quebec.
AB  - BACKGROUND: To study the incidence, persistence, and determinants of human
      papillomavirus (HPV) infection in a population of Inuit women from Nunavik,
      Quebec, by overall HPV infection, Alphapapillomavirus (alpha) species, and
      oncogenic risk grouping. METHODS: We recruited a cohort of Inuit women living in
      communities in Nunavik when they presented for routine care. Baseline
      sociodemographic and lifestyle characteristics were collected and cervical
      specimens collected throughout the follow-up period were tested for HPV-DNA using
      the PGMY Line-blot assay. RESULTS: A total of 416 women were eligible for this
      analysis. Almost 40% of women acquired a new any-type HPV infection, at a rate of
      14.44 infections per 1000 women-months. High-risk HPV infections were acquired at
      a higher rate than low-risk infections and persisted for longer durations.
      Multivariate logistic regression found age and marital status to be the most
      important predictors of overall HPV infection acquisition. Over the study period,
      36.1% of women cleared their incident infections. The cumulative incidence of any
      HPV type at 12 months was 10.3% (95% confidence interval, 7.9-13.1). No
      predictors of clearance were found. CONCLUSIONS: The high incidence and
      persistence of HPV infections found demonstrate that this population is at high
      risk for HPV infection. These data provide a deeper understanding of the HPV
      infection experience of Inuit women, but they may also help evaluate vaccination
      strategies currently used for this high-risk population.

PMID- 25868141
TI  - Failure of azithromycin 2.0 g in the treatment of gonococcal urethritis caused by
      high-level resistance in California.
AB  - We report a treatment failure to azithromycin 2.0 g caused by a urethral
      Neisseria gonorrhoeae isolate with high-level azithromycin resistance in
      California. This report describes the epidemiological case investigation and
      phenotypic and genetic characterization of the treatment failure isolate. 

PMID- 25868142
TI  - Sexual behaviors and HIV/syphilis testing among transgender individuals in China:
      implications for expanding HIV testing services.
AB  - BACKGROUND: HIV and syphilis are disproportionately common among transgender
      individuals globally, yet few studies have investigated transgender HIV/syphilis
      risk and testing in low- and middle-income nations. We conducted an online survey
      of men who have sex with men (MSM) and transgender individuals to examine sexual
      behaviors and HIV/syphilis testing in China. METHODS: We recruited MSM and
      transgender individuals from 2 major Chinese lesbian, gay, bisexual, and
      transgender Web platforms. chi Test and logistic regression were used to compare
      risk behaviors, HIV and syphilis testing history, and prevalence between
      transgender individuals and other MSM. RESULTS: Among the 1320 participants, 52
      (3.9%) self-identified as transgender. Demographics, including education,
      employment, and marital status, were similar between both groups, whereas
      transgender individuals were older. Condomless anal intercourse rate was
      comparable between the groups. Transgender individuals were less likely to report
      ever testing for HIV (34.6% vs. 62.0%) and syphilis (15.7% vs. 31.2%) with
      adjusted odds ratios of 0.36 (95% confidence interval, 0.20-0.65) and 0.42 (95%
      confidence interval, 0.20-0.91), respectively. We found a trend toward a higher
      HIV prevalence among transgender individuals (11.1% vs. 5.7%, P = 0.12).
      CONCLUSIONS: Transgender individuals have suboptimal HIV and syphilis testing
      rates in China. Given the substantial risk behaviors and burden of HIV/STI in the
      general Chinese MSM population and a lack of knowledge about transgender
      individuals, enhanced HIV/syphilis testing programs for transgender individuals
      in China are needed.

PMID- 25868143
TI  - Sexually transmitted infection clinics as safety net providers: exploring the
      role of categorical sexually transmitted infection clinics in an era of health
      care reform.
AB  - BACKGROUND: For many individuals, the implementation of the US Affordable Care
      Act will involve a transition from public to private health care venues for
      sexually transmitted infection (STI) care and prevention. To anticipate
      challenges primary care providers may face and to inform the future role of
      publicly funded STI clinics, it is useful to consider their current functions.
      METHODS: Data collected by 40 STI clinics that are a part of the Sexually
      Transmitted Disease Surveillance Network were used to describe patient
      demographic and behavioral characteristics, STI diagnoses, and laboratory testing
      data in 2010 and 2011. RESULTS: A total of 608,536 clinic visits were made by
      363,607 unique patients. Most patients (61.9%) were male; 21.9% of men reported
      sex with men (MSM). Roughly half of patients were 20 to 29 years old (47.1%) and
      non-Hispanic black (56.2%). There were 212,765 STI diagnoses (mostly
      nonreportable) that required clinical examinations. A high volume of chlamydia,
      gonorrhea, and HIV testing was performed (>350,000 tests); the prevalence was
      11.5% for chlamydia, 5.8% for gonorrhea, 0.9% for HIV, and varied greatly by sex
      and MSM status. Among MSM with chlamydia or gonorrhea, 40.1% (1811/4448) of
      chlamydial and 46.2% (3370/7300) of gonococcal infections were detected at
      extragenital sites. CONCLUSIONS: Sexually Transmitted Disease Surveillance
      Network clinics served populations with high STI rates. Given experience with
      diagnoses of both nonreportable and reportable STIs and extragenital chlamydia
      and gonorrhea testing, STI clinics comprise a critical specialty network in STI
      diagnosis, treatment, and prevention.

PMID- 25868144
TI  - What is the role of sexually transmitted disease clinics?

PMID- 25868145
TI  - Environmental regulations on air pollution in China and their impact on infant
      mortality.
AB  - This study explores the impact of environmental regulations in China on infant
      mortality. In 1998, the Chinese government imposed stringent air pollution
      regulations, in one of the first large-scale regulatory attempts in a developing
      country. We find that the infant mortality rate fell by 20 percent in the
      treatment cities designated as "Two Control Zones." The greatest reduction in
      mortality occurred during the neonatal period, highlighting an important
      pathophysiologic mechanism, and was largest among infants born to mothers with
      low levels of education. The finding is robust to various alternative hypotheses
      and specifications. Further, a falsification test using deaths from causes
      unrelated to air pollution supports these findings. 

PMID- 25868147
TI  - Regulation of smooth muscle contractility by competing endogenous mRNAs in
      intracranial aneurysms.
AB  - Alterations in vascular smooth muscle cells (SMCs) contribute to the pathogenesis
      of intracranial aneurysms (IAs), but the genetic mechanisms underlying these
      alterations are unclear. We used microarray analysis to compare tissue small
      noncoding RNA and messenger RNA expression profiles in vessel wall samples from
      patients with late-stage IAs. We identified myocardin (MYOCD), a key
      contractility regulator of vascular SMCs, as a critical factor in IA progression.
      Using a multifaceted computational and experimental approach, we determined that
      depletion of competitive endogenous RNAs (ARHGEF12, FGF12, and ADCY5) enhanced
      factors that downregulate MYOCD, which induces the conversion of SMCs from
      differentiated contractile states into dedifferentiated phenotypes that exhibit
      enhanced proliferation, synthesis of new extracellular matrix, and organization
      of mural thrombi. These effects may lead to the repair and maintenance of IAs.
      This study presents guidelines for the prediction and validation of the IA
      regulator MYOCD in competitive endogenous RNA networks and facilitates the
      development of novel therapeutic and diagnostic tools for IAs. 

PMID- 25868148
TI  - Effects of postmortem interval on biomolecule integrity in the brain.
AB  - Postmortem brain research is invaluable to the study of neurologic and
      neuropsychiatric disorders, including Alzheimer disease, schizophrenia, and major
      depression. A major confounder in molecular studies using human brain tissue is
      postmortem interval (i.e. the amount of time between a subject's death and
      processing of tissue). We examined the integrity of biomolecules that were of
      interest to molecular studies of neurologic disorders, including RNA, microRNA,
      histone modifications, and proteins, at various postmortem intervals in an animal
      model to assess their robustness and suitability for experimentation. Sprague
      Dawley rats were selected as model and subjected to 2 conditions: a variable
      postmortem interval at room temperature and a fixed time of 24 hours at 4 degrees
      C, which simulates the period commonly spent in the morgue before brain
      collection. Eight time points were investigated. MicroRNA was impressively
      resistant to postmortem intervals; methylated histone modifications showed a
      threshold between 72 and 96 hours, mirroring results from histone proteins at 72
      hours. RNA degradation was transcript-specific, with housekeeping genes being
      more robust than genes with lower expression. Our results suggest that molecules
      commonly investigated in genetic and epigenetic studies were highly stable
      through the postmortem intervals investigated. These results support the
      continued use of postmortem tissue for neuropsychiatric research.

PMID- 25868149
TI  - Correlations between mini-mental state examination score, cerebrospinal fluid
      biomarkers, and pathology observed in brain biopsies of patients with normal
      pressure hydrocephalus.
AB  - Alzheimer disease (AD)-related pathology was assessed in cortical biopsy samples
      of 111 patients with idiopathic normal-pressure hydrocephalus. Alzheimer disease
      hallmark lesions-beta-amyloid (Abeta) and hyperphosphorylated tau (HPtau)-were
      observed in 47% of subjects, a percentage consistent with that for whole-brain
      assessment reported postmortem in unselected cohorts. Higher-immunostained area
      fraction of AD pathology corresponded with lower preoperative mini-mental state
      examination scores. Concomitant Abeta and HPtau pathology, reminiscent of that
      observed in patients with AD, was observed in 22% of study subjects. There was a
      significant correlation between Abeta-immunostained area fraction in tissue and
      Abeta42 (42-amino-acid form of Abeta) in cerebrospinal fluid (CSF). Levels of
      Abeta42 were significantly lower in CSF in subjects with concomitant Abeta and
      HPtau pathology compared with subjects lacking pathology. Moreover, a significant
      correlation between HPtau-immunostained area fraction and HPtau in CSF was noted.
      Both HPtau and total tau were significantly higher in CSF in subjects with
      concomitant Abeta and HPtau pathology compared with subjects lacking pathology.
      The 42-amino-acid form of Abeta (Abeta42) and HPtau in CSF were the most
      significant predictors of the presence of AD pathology in cortical biopsies. Long
      term follow-up studies are warranted to assess whether all patients with
      idiopathic normal-pressure hydrocephalus with AD pathology progress to AD and to
      determine the pathologic substrate of idiopathic normal-pressure hydrocephalus. 

PMID- 25868150
TI  - Language control in bilinguals: Intention to speak vs. execution of speech.
AB  - Bilinguals require a high degree of cognitive control to select the language
      intended for speaking and inhibit the unintended. Previous neuroimaging studies
      have not teased apart brain regions for generating the intention to use a given
      language, and those for speaking in that language. Separating these two phases
      can clarify at what stage competition between languages occurs. In this fMRI
      study German-English bilinguals were first cued to use German or English. After a
      delay, they named a picture in the cued language. During the intention phase, the
      precuneus, right superior lateral parietal lobule, and middle temporal gyrus were
      more activated when participants had to update the currently active language.
      During language execution activation was higher for English compared to German in
      brain areas associated with cognitive control, most notably the anterior
      cingulate and the caudate. Our results suggest two different systems enabling
      cognitive control during bilingual language production. 

PMID- 25868152
TI  - Ecotoxicological risks of calcium nitrate exposure to freshwater tropical
      organisms: Laboratory and field experiments.
AB  - This study aimed to analyze laboratory and field data to assess the
      ecotoxicological risks of calcium nitrate exposure to freshwater tropical biota.
      Short-term laboratorial tests resulted in estimated EC50 values of 76.72 (67.32
      86.12)mg N-NO3- L(-1) for C. silvestrii and 296.46 (277.16-315.76) mg N-NO3- L(
      1) for C. xanthus. Long-term laboratorial tests generated IC25 values of 5.05
      (4.35-5.75) and 28.73 (26.30-31.15) mg N-NO3- L(-1) for C. silvestrii and C.
      xanthus, respectively. The results from in situ mesocosm experiments performed in
      the Ibirite reservoir (a tropical eutrophic urban water body located in SE
      Brazil) indicated that C. silvestrii and C. xanthus were not under severe
      deleterious acute impact due to the treatment because the higher nitrate
      concentrations determined were 5.2 mg N-NO3- L(-1) (t=24 h; sediment-water
      interface) and 17.5 mg N-NO3- L(-1) (t=600 h; interstitial water). However, an
      abrupt decrease in the densities of Cyanophyceae members and other benthic taxa
      was observed. In summary, the present work contributes greatly to the toxicity
      data linked to two taxonomically distinct organisms that have never been screened
      for calcium nitrate sensitivity. Furthermore, considering the problem of the
      management and restoration of eutrophic environments, our study reports a
      comprehensive field assessment that allows the elucidation of the possible toxic
      impacts caused by the addition of calcium nitrate (a remediation technique) on
      aquatic and benthic organisms as well as the implications on the aquatic
      ecosystem as a whole, which may greatly allow expanding the current knowledgebase
      on the topic.

PMID- 25868151
TI  - Adapted approach to profile genes while reconciling Vegf-a mRNA expression in the
      developing and injured lung.
AB  - During lung development and injury, messenger RNA (mRNA) transcript levels of
      genes fluctuate over both space and time. Quantitative PCR (qPCR) is a highly
      sensitive, widely used technique to measure the mRNA levels. The sensitivity of
      this technique can be disadvantageous and errors amplified when each qPCR assay
      is not validated. In contrast to other organs, lungs have high RNase activity,
      resulting in less than optimal RNA integrity. We implemented a strategy to
      address these limitations in developing and injured lungs. Parameters were
      established and a filter designed that optimized amplicon length and included or
      excluded samples based on RNA integrity. This approach was illustrated and
      validated by measuring mRNA levels including Vegf-a in newborn mouse lungs that
      were injured by 85% oxygen (hyperoxia) for 12 days and compared with control
      (normoxia). We demonstrate that, in contrast to contradictory Vegf-a expression
      when normalized to the least suitable housekeeping genes, application of this
      filter and normalization to most suitable three housekeeping genes, Hprt, Eef2,
      and Rpl13a, gave reproducible Vegf-a expression, thus corroborating the sample
      filter. Accordingly, both short amplicon length and proper normalization to
      ranked, evaluated genes minimized erroneous fluctuation and qPCR amplification
      issues associated with nonideal RNA integrity in injured and developing lungs.
      Furthermore, our work uncovers how RNA integrity, purity, amplicon length, and
      discovery of stable candidate reference genes enhance precision of qPCR results
      and utilizes the advantages of qPCR in developmental studies. 

PMID- 25868153
TI  - Combined Surgical Treatment in Breast Cancer-Related Lymphedema.
AB  - BACKGROUND: Lymphedema is a well-known sequela of breast but no consensus has
      been reached about the ideal treatment. Surgical approaches, however, are
      receiving increased attention. Various microsurgical reconstructive techniques
      aim to restore anatomy and function of the lymphatic system in upper limb breast
      cancer-related lymphedema (BCRL). We combined two techniques, lymphaticovenous
      anastomosis (LVA) and autologous lymph node transplantation (ALNT) after
      carefully selecting those who may benefit from the surgery. We called this the
      "combined surgical treatment (CST)" approach. METHODS: From June 2007 to December
      2011, we performed CST in 106 patients with upper limb BCRL. Clinical evaluation
      and diagnostic imaging studies were performed preoperatively in all the patients.
      CST was offered to patients with stage I/II lymphedema, according to the criteria
      of the International Society of Lymphology (ISL). RESULTS: Overall 59 of the 106
      patients underwent LVA, 7 underwent ALNT, and 40 underwent both the techniques.
      All 47 lymph node (LN)-flaps survived but 11 (22%) required surgical revision
      within 3 days. A total of 21 LN-flaps (45%) showed no radiotracer uptake at 1
      year. Around 1 to 7 LVAs for each patient (average 3.4) were performed.
      Preoperative versus postoperative excess circumference decreased between 12 and
      86.7% (average 39.72%). Arm circumference decreased between 0.9 and 6.1 cm
      (average 2.75 cm). The number of episodes of lymphangitis per year decreased from
      1.8 to 0.2. CONCLUSION: Preoperative assessment is essential to select patients
      who can benefit from surgery for lymphedema and to choose the best surgical
      approach in each case. Our satisfactory results in well-selected cases encourage
      further research into surgical treatment for BCRL.

PMID- 25868154
TI  - Four-Dimensional (4D) Printing: A New Evolution in Computed Tomography-Guided
      Stereolithographic Modeling. Principles and Application.
AB  - BACKGROUND: Over the last decade, image-guided production of three-dimensional
      (3D) haptic biomodels, or rapid prototyping (RP), has transformed the way
      surgeons conduct preoperative planning. In contrast to earlier RP techniques such
      as stereolithography, 3D printing has introduced fast, affordable office-based
      manufacturing. We introduce the concept of 4D printing for the first time by
      introducing time as the fourth dimension to 3D printing. METHODS: The bones of
      the thumb ray are 3D printed during various movements to demonstrate four
      dimensional (4D) printing. Principles and validation studies are presented here.
      RESULTS: 4D computed tomography was performed using "single volume acquisition"
      technology to reduce the exposure to radiation. Three representative scans of
      each thumb movement (i.e., abduction, opposition, and key pinch) were selected
      and then models were fabricated using a 3D printer. For validation, the angle
      between the first and the second metacarpals from the 4D imaging data and the 4D
      printed model was recorded and compared. CONCLUSION: We demonstrate how 4D
      printing accurately depicts the transition in the position of metacarpals during
      thumb movement. With a fourth dimension of time, 4D printing delivers complex
      spatiotemporal anatomical details effortlessly and may substantially improve
      preoperative planning.

PMID- 25868155
TI  - Diaphragmatic reinnervation in ventilator-dependent patients with cervical spinal
      cord injury and concomitant phrenic nerve lesions using simultaneous nerve
      transfers and implantable neurostimulators.
AB  - BACKGROUND: Patients who are ventilator dependent as a result of combined
      cervical spinal cord injury and phrenic nerve lesions are generally considered to
      be unsuitable candidates for diaphragmatic pacing due to loss of phrenic nerve
      integrity and denervation of the diaphragm. There is limited data regarding
      efficacy of simultaneous nerve transfers and diaphragmatic pacemakers in the
      treatment of this patient population. METHODS: A retrospective review was
      conducted of 14 consecutive patients with combined lesions of the cervical spinal
      cord and phrenic nerves, and with complete ventilator dependence, who were
      treated with simultaneous microsurgical nerve transfer and implantation of
      diaphragmatic pacemakers. Parameters of interest included time to recovery of
      diaphragm electromyographic activity, average time pacing without the ventilator,
      and percent reduction in ventilator dependence. RESULTS: Recovery of diaphragm
      electromyographic activity was demonstrated in 13 of 14 (93%) patients. Eight of
      these 13 (62%) patients achieved sustainable periods (> 1 h/d) of ventilator
      weaning (mean = 10 h/d [n = 8]). Two patients recovered voluntary control of
      diaphragmatic activity and regained the capacity for spontaneous respiration. The
      one patient who did not exhibit diaphragmatic reinnervation remains within 12
      months of initial treatment. Surgical intervention resulted in a 25% reduction (p
      < 0.05) in ventilator dependency. CONCLUSION: We have demonstrated that
      simultaneous nerve transfers and pacemaker implantation can result in
      reinnervation of the diaphragm and lead to successful ventilator weaning. Our
      favorable outcomes support consideration of this surgical method for appropriate
      patients who would otherwise have no alternative therapy to achieve sustained
      periods of ventilator independence.

PMID- 25868157
TI  - [The usefulness of wireless ambulatory pH monitoring for prediction of response
      to proton pump inhibitor treatment in patients with globus sense].

PMID- 25868156
TI  - Re: Exposure to indoor tanning without burning and melanoma risk by sunburn
      history.

PMID- 25868158
TI  - [Asymptomatic accessory bile duct draining into the stomach].

PMID- 25868159
TI  - [Is the location of diverticular disease associated with irritable bowel
      syndrome?].

PMID- 25868160
TI  - Multi-resistant bacteria--recent trends in emerging zoonotic agents.

PMID- 25868162
TI  - [Statistical methods for description of phenotypic susceptibility data].
AB  - This paper summarizes statistical methods to describe susceptibility data. A
      frequent data basis in resistance studies are minimum inhibitory concentrations
      (MICs), measured for different antimicrobial agents. In the statistical context
      these (semi) quantitative MIC values are ordinal scaled. Therefore, they should
      be analysed with statistical tools appropriate for ordinal data. The resistance
      situation for each antimicrobial agent is often described using frequency
      distributions of MIC values. Resistance patterns can be described by frequencies
      of resistance profiles. More detailed insights into appearance and changes of
      simultaneous resistance against different agents are provided by a systematic
      analysis of dependency structure in susceptibility data. Furthermore, the
      calculation of differences between resistance profiles using appropriate distance
      measures enables the application of common methods of multivariate statistic for
      description and more complex analysis of susceptibility data. To improve the
      comparability of study results, it is desirable to present as much information as
      possible in a uniform way.

PMID- 25868161
TI  - [Antimicrobial resistance, ESBL and MRSA--definitions and laboratory
      diagnostics].
AB  - In the light of frequent discussions about the correct performance of in vitro
      susceptibility testing and the interpretation of the results obtained, the aim of
      the present report is to summarize basic facts that may facilitate the
      understanding of this complex topic. For this, the terms "antimicrobial
      resistance", "ESBL", and "MRSA" are defined. Besides the statements on
      antimicrobial resistance, information on intrinsic and acquired resistance
      properties as well as basic rules for the correct performance of antimicrobial
      susceptibility testing in routine diagnostics are presented. Moreover, the two
      groups of interpretive criteria--clinical breakpoints and epidemiological cut-off
      values--including their applications are explained in detail. Furthermore,
      currently valid diagnostic procedures--as published by the European Committee on
      Antimicrobial Susceptibility Testing (EUCAST) and the Clinical and Laboratory
      Standards Institute (CLSI)--for the screening of ESBL-producing
      Enterobacteriaceae and MRSA as well as for the confirmation of suspicious
      isolates are presented and compared. Based on the information given, it becomes
      obvious that the correct performance of the diagnostic tests, which includes
      strict following the performance standards and the detailed information given
      therein, is an indispensable prerequisite for a standardized and harmonized in
      vitro susceptibility testing and--as a consequence--for the determination of
      valid and reliable susceptibility data in routine diagnostics. This is of utmost
      importance since the susceptibility data based on the use of clinical breakpoints
      often represent the basis for therapeutic interventions.

PMID- 25868163
TI  - Analysis of the distribution of veterinary antimicrobial products to
      veterinarians in Germany in 2011 and 2012.
AB  - For the implementation of risk management measures against the development and
      spread of antimicrobial resistances it is important to gain a quantitative
      insight into the use of veterinary antimicrobial agents. Since 2011, all
      pharmaceutical companies and wholesalers in Germany are required to report their
      sales data of veterinary antimicrobial products (VAPs). In 2011, 1706 t of
      antimicrobially active substances were sold to veterinarians registered in
      Germany, in 2012 the amount decreased to 1619 t. Tetracyclines and penicillins
      had the largest shares in both years, followed by sulfonamides, macrolides and
      polypeptides. Amoxicillin alone accounted for more than a quarter of the total
      amounts of all sold antimicrobials. In regard to AMR it is most important to
      limit the use of critically important antimicrobials, namely fluoroquinolones and
      3rd and 4th generation cephalosporins. While in both years these groups accounted
      for less than 1% of the amount of sold antimicrobials, this does not reflect
      adequately their use, since they are used in much lower doses. Furthermore, it is
      worrying that the sales of fluoroquinolones and 3rd generation cephalosporins
      increased by 26% and 14%, respectively, between 2011 and 2012, while the sales of
      4th generation cephalosporins decreased only by 2%. More than 95% of the active
      substances were contained in VAPs intended for oral application; only
      fluoroquinolones, 3rd and 4th generation cephalosporins as well as fenicols were
      primarily or even exclusively applied by injection.

PMID- 25868164
TI  - [Antibiotic usage and antibiotic sales in Germany in 2011--the situation of drug
      usage in veterinary medicine].
AB  - To appreciate the significance of sales data of antibiotics, data on antibiotic
      consumption (which were collected for selected food-producing animals within the
      representative VetCAb pilot study in Germany in 2011) were extrapolated for the
      total German animal population, and subsequently compared to the antibiotic sales
      data, which were collected throughout Germany in 2011 for the first time and
      which were published by the Federal Office of Consumer Protection and Food Safety
      (BVL). The extrapolation was realized based on the average dosage and the number
      of treatment units determined in the VetCAb pilot project for each active
      ingredient and animal species. It was extrapolated that 1302 tons of
      antimicrobial substances were consumed for treating cattle, pigs and broilers-
      this amount is accompanied by the amount of 1706 tons sold for all animal
      species. In Germany, tetracyclines and beta-lactams are the most commonly used
      and sold antimicrobial drugs. In third place are the potentiated sulfonamide, in
      fourth and fifth place, macrolides and polypeptides. To describe and evaluate the
      antibiotic usage for the several food-producing animals, detailed information is
      needed. Therefore, the number of treatments per active ingredient per animal and
      per day (treatment unit), and the number of treatment days per active ingredient
      per animal (treatment frequency) were calculated in the VetCAb project. These
      values represent scientifically collected orientation values for the treatment
      frequency of food-producing animal with antimicrobial substances in Germany. For
      example, a fattening pig is treated at 4.2 days (median) with one active
      ingredient within its 115-day fattening period. A dairy cow is treated at 3.5
      days with one active ingredient within one year. A broiler is treated at 10 days
      with one active ingredient within its 39-day production period.

PMID- 25868165
TI  - The use of the "highest priority critically important antimicrobials" in 75
      Austrian pig farms--evaluation of on-farm drug application data.
AB  - The World Health Organization lists antimicrobial substances which are essential
      for the treatment of specific infections in humans as "highest priority
      critically important antimicrobials" (HPCIAs): macrolides, fluoroquinolones, 3rd
      and 4th generation cephalosporins as well as glycopeptid antibacterials. The use
      of these substances in livestock husbandry should be restricted in order to
      minimise the risk of antimicrobial resistance. To date, there is little knowledge
      about the amounts of HPCIAs used in animal husbandry and the different animal
      species and diagnoses these antimicrobials are prescribed for. In a retrospective
      study, drug application data recorded from 2008 until 2011 from 75 conventional
      pig farms were evaluated. Data were assessed directly by the farmer at farm
      level. The annual antimicrobial consumption was expressed in "weight of active
      substance(s) in [mg]" and "number of Daily Doses". Results were referred to the
      animal biomass, evaluated per pig age class (piglets, weaners, fattening pigs <
      60 kg biomass; fattening pigs > 60 kg biomass, sows, boars) and broken down to
      some variables such as the substance class and the therapy indication. The focus
      was especially laid on the HPCIAs. The total usage of the HPCIAs in the study
      population was on average 3.0 mg/ kg/year; 1.1 UDD(kg)/kg/year; 0.2
      ADD(kg)/kg/year and 0.6 PrDD(kg)/kg/year. This represents about 9%, 22%, 12% and
      22% of total antimicrobial consumption, respectively, depending on the unit of
      measurement. Fattening farms showed the highest consumption of the named
      substances. The main part of the HPCIAs (nADD(kg)/year) was applied to weaners,
      piglets and fattening pigs < 60 kg. They played an important role in the
      therapies of piglets (approximately 40% of the total antimicrobial consumption in
      piglets). Macrolides played the major role within the HPCIAs and were mainly used
      for digestive tract diseases. A not negligible portion of macrolides was
      prescribed for metaphylactic and prophylactic measures.

PMID- 25868166
TI  - The impact of zoonotic MRSA colonization and infection in Germany.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) causes colonization and
      infection both in animals and humans. In Germany, cases of MRSA colonization
      among humans, w+hich affect 0.5-1.5% of the general population and 1.0-2.5% of
      patients at hospital admission, are still mostly associated with previous
      healthcare contact and defined epidemic clonal lineages. However, MRSA is also
      distributed in livestock production in Germany, mostly without causing infections
      in the animals. These MRSA predominantly belong to the clonal complex (CC) 398,
      but also to CC9 and CC97. Zoonotic transmission of MRSA CC398 from livestock to
      humans occurs predominantly in people with occupational livestock contact. Spread
      of MRSA CC398 to household members of these persons is also frequently observed,
      but dissemination in the general population is limited so far However, especially
      in areas with intensive livestock husbandry, about 20-38% of MRSA CC398 cases
      among humans cannot be epidemiologically linked to direct livestock contact,
      indicating other transmission pathways. MRSA CC398 currently causes about 2% of
      all human MRSA infections (wound infections, pneumonia, sepsis) in Germany, but
      up to 10% in regions characterized by a high density of livestock-farming. The
      burden of MRSA in companion animals was demonstrated to range between 3.6-9.4%
      within wound samples obtained from dogs, cats and horses, respectively. In
      contrast to livestock and horses, MRSA distributed in pet animals are mostly
      associated with MRSA clonal lineages that are also prevalent in human healthcare
      facilities. Overall, zoonotic exchange of MRSA between humans and animals has
      relevant impact on the epidemiology of MRSA in Germany.

PMID- 25868167
TI  - [MRSA and ESBL in outpatient: development from 2008 up to 2012 and socio
      demographic differences].
AB  - Data on resistance from ambulatory care are rarely available, since surveillance
      systems cover mostly isolates come from inpatient care. The outpatient setting is
      of interest, however, since it is where hospitalized patients with resistant
      pathogens are also treated as outpatients, and where patients are seen who have
      resistant pathogens from other sources, such as food. In addition, 85% of the
      antibiotics used in human medicine, are used in ambulatory care. Using data from
      the Antibiotic Resistance Surveillance System (ARS), we show the development of
      resistance of Staphylococcus aureus to oxacillin and of Escherichia coli and
      Klebsiella pneumoniae to cefotaxime in outpatient care between 2008 and 2012 and
      corresponding socio-demographic differences in the resistance rate. According to
      our analyses, the proportion of MRSA in S. aureus since 2009 in the outpatient
      sector decreased (all materials: 2009 11.5%, 2012 9.8%), which is similar to
      inpatient care, while the proportion of ESBL in E. coli (2008 2.7%, 2012 5.6%),
      and K. pneumoniae (2008 2.7%, 2012 6.6%) increased over the total period. At the
      same time resistance for the three pathogens in both sexes over the age groups
      continuously increased, women still hold a lower proportion of resistance than
      men. The resistance levels of S. aureus and K. pneumoniae in ambulatory care are
      reflected at a lower level than in hospital care. In contrast, the high
      proportion of resistant E. coli in children suggests another source in ambulatory
      care.

PMID- 25868168
TI  - [On the occurence of extended-spectrum- and AmpC-beta-lactamase-producing
      Escherichia coli in livestock: results of selected European studies].
AB  - Extended-spectrum-beta-lactamase (ESBL) and plasmid-encoded cephamycinase (pAmpC)
      producing Escherichia (E.) coli in livestock farms have recently been matter of
      growing scientific and public concern. This article summarises selected European
      studies which focus on the prevalence and risk factors associated with the
      presence of such resistant E. coli isolates in livestock farms. Due to the
      different methodologies used in these studies, they cannot be compared directly;
      nonetheless, the overall prevalence found is very high. The prevalence found in
      broiler farms was higher than 40% and the individual animal prevalence was ca.
      30%. The prevalence was more variable in pigs, with reports of pig farms showing
      prevalence of 1 to 80% and reports of individual animal prevalence of 15 to 100%
      In studies on cattle farms the production type as well as the age of animals had
      an influence on the number of positive samples. The highest prevalence was found
      with calves after birth and in the first weeks, whereas with older cattle the
      numbers of positive samples were considerably lower. Samples taken from dairy
      cows were positive more often after calving than before calving. According to the
      livestock species different risk factors may be assessed for the occurrence of
      ESBL/pAmpC-producing E. coli isolates. In some studies an association between the
      occurrence of ESBL-producing E. coli and factors like the use of antimicrobial
      agents or management factors, as the duration of the fattening period and the
      acquisition of animals from different origins, were identified. At the moment,
      there is a lack of systematic and standardised transnational epidemiological
      investigations on the occurrence of ESBL/pAmpC-producing E. coli in livestock. To
      control the further spread of ESBL/pAmpC-producing E. coli and the effectiveness
      of preventive measures, comprehensive monitoring and surveillance systems with
      harmonised methods are essential. Modern typing methods, in particular the
      sequence-based methods, can provide more information to clarify transmission
      pathways.

PMID- 25868169
TI  - Extended-spectrum beta-lactamases (ESBL)/AmpC beta-lactamases-producing
      Escherichia coli in German fattening pig farms: a longitudinal study.
AB  - The presence of ESBL/AmpC-producing Enterobacteriaceae in healthy livestock, such
      as pigs, was frequently reported worldwide in the last years. The development and
      potential spread of these resistant microorganisms in farm animals is discussed
      critically. Therefore, the main objectives of this longitudinal study were to
      determine potential sources and prevalence dynamics of ESBL/AmpC-producing
      Escherichia coli in seven German ESBL/AmpC-positive conventional fattening pig
      farms in the course of the fattening period. Samples tested were taken at three
      different times within one finishing fattening period and included 20 individual
      faeces samples as well as various samples of the animals' housing environment
      such as pooled faeces, boot swabs, dust and environmental swabs. In individual
      faeces average carriage levels of 45%, 29% and 36% at the three sampling times
      were accompanied by decreasing faecal counts from 2.97 x 10(4) cfu/g at the first
      to 2.17 x 10(3) cfu/g at the third visit. In the animals' housing environment
      47.6% of pooled faeces and boot swab samples respectively and 5.9% of
      environmental swabs but none of the dust samples were tested positive. Altogether
      228 E. coli isolates were analysed by combination disc tests, PCR and partly via
      sequencing.Thereby, a novel gene bla(TEM-206) was detected. This study shows
      different detection levels of ESBL/AmpC-producing E. coli amongst the different
      farms and in the course of the fattening period. Pooled faeces and boot swab
      samples but not dust samples seem to be appropriate to assess the herd status of
      pigs with respect to ESBL/AmpC-producing Escherichia coli.

PMID- 25868171
TI  - Diagnostic approaches to anemia.
AB  - The best of all the approaches to anemia in children is the rational approach,
      which consists of a logical sequence of questions. Appropriate answers can be
      found within the physician's office in the vast majority of cases.

PMID- 25868172
TI  - Diagnosis and management of disseminated intravascular coagulation.
AB  - Disseminated intravascular coagulation (defibrination syndrome, consumption
      coagulopathy) is a syndrome which may complicate a number of pathologic states.
      If clotting factors and platelets are "consumed" more rapidly than the patient
      can produce them, they may fall to levels which are not adequate for hemostasis.
      Thus, thrombosis with resulting necrosis and hemorrhage may occur simultaneously
      in the same patient. Local fibrinolysis (secondary fibrinolysis) may remove or
      partially remove intravascular thrombi, thus protecting against local tissue
      necrosis. Diagnosis of the fulminating syndrome is usually simple and depends
      upon a few relatively easy tests. If the syndrome is low grade, diagnosis is very
      difficult and may be impossible without sophisticated techniques. Differential
      diagnosis from coagulation defects secondary to liver disease is extremely
      difficult. Treatment in the fulminating case before intravascular thrombi can
      cause irreversible tissue damage is urgent. Treatment depends upon therapy of the
      underlying disease plus adequate heparinization. It may be necessary to
      administer platelets and blood fractions after heparinization. Corticosteroids
      are not contraindicated, particularly when the patient is heparinized. Epsilon
      amino-caproic acid (EACA, Amicar) is contraindicated. This drug inhibits local
      fibrinolysis, which is protective to the patient.

PMID- 25868173
TI  - Diagnosis of lupus erythematosus and rheumatoid arthritis in children.
AB  - Laboratory tests are of importance in differentiating lupus erythematosus from
      rheumatoid arthritis, and in distinguishing between the two forms of lupus,
      because an accurate understanding of the nature of the disease determines
      rational therapy.

PMID- 25868174
TI  - The diagnosis of immune deficiency diseases.
AB  - The functions of the immune system, divided into three types, are conceived as
      the basis for classification of immune deficiency disorders, and useful
      laboratory procedures are reviewed.

PMID- 25868175
TI  - Diagnostic virology.
AB  - A review of the indications for viral diagnostic procedures has been presented.
      Specific diagnosis is unnecessary and impractical in every patient with a
      suspected viral illness. In certain instances, however, the documentation of a
      viral disease by culture or serology may be of great value to the patient. The
      pediatrician must therefore use his judgment as to when to study the patient, and
      should resist the temptation simply to tell an anxious parent, "Don't worry; it's
      just a virus".

PMID- 25868176
TI  - The diagnosis of rubella.
AB  - A review of the immunology of rubella and the basic requirements of various
      laboratory tests used in its diagnosis.

PMID- 25868177
TI  - Immunoglobulin determinations in the diagnosis of fetal infection.
AB  - Current indications are that the human fetus is not immunologically incompetent.
      An elevated IgM level may be a nonspecific indicator of a newborn at high risk
      for intrauterine infections--which may not be clinically apparent.

PMID- 25868178
TI  - Laboratory assistance in the treatment of bacterial infections.
AB  - The microbiology laboratory can assist the clinician in the treatment of
      bacterial infections by isolating and identifying the responsible organisms and
      by determining their susceptibility to antibiotic drugs.

PMID- 25868179
TI  - Diagnosis of streptococcal pharyngitis and rheumatic fever.
AB  - Eradication of streptococci from the throat has been shown to prevent rheumatic
      fever, so that an accurate diagnosis of streptococcal pharyngitis is desirable.
      Throat cultures could be better utilized than they have been for this purpose.

PMID- 25868180
TI  - Identification and treatment of group A beta-hemolytic streptococcal infections.
      Role of the pediatrician and the nurse-practitioner.
AB  - The risk of rheumatic fever in childhood continues to be high in the United
      States, especially where crowded living conditions promote epidemic spread of
      streptococcal pharyngitis. Early identification and appropriate penicillin
      therapy shorten the acute streptococcal illness and greatly reduce the occurrence
      of sequelae. Florid disease usually presents no therapeutic dilemma, but a firm
      scientific basis for definitive diagnosis and treatment of the carrier state,
      inapparent infection, mild clinical disease, or relapse is lacking. Appreciation
      of these unresolved issues is helpful in developing practical therapeutic
      guidelines for physicians and assistants. Public health throat culture programs
      may provide the initiative for effective community streptococcal control, but
      centralization of facilities on a large scale may delay institution of therapy
      because of slow reporting of culture results. Although delay in treatment may
      engender increased risk of rheumatic fever, institution of appropriate penicillin
      therapy may prevent rheumatic fever even if started after an untreated
      streptococcal tonsillitis has run its usual 5 day symptomatic course. Throat
      cultures are necessary in diagnosis, but clinical judgment must be exercised in
      initiating penicillin therapy before the culture is reported. The relative
      morbidity and ultimate mortality of the sequelae to streptococcal disease suggest
      assignment of national health priority to the development of preventive programs.
      Utilization of nurse-practitioners or similarly trained medical assistants seems
      necessary to effective delivery of care in the crowded areas of highest rheumatic
      fever incidence.

PMID- 25868181
TI  - Screening tests for Head Start children.
AB  - Meeting physical and emotional needs of children through health, nutritional, and
      social services is a prerequisite to academic achievement, and the Head Start
      program requires screening tests of all enrolled.

PMID- 25868182
TI  - Test development in the pediatric multiphasic program.
AB  - The need for multiphasic screening tests in children lies in three major areas:
      detection of chronic complications of acute conditions, detection of
      abnormalities that might contribute to acute conditions, and detection of chronic
      invidious conditions in which early intervention might be beneficial.

PMID- 25868183
TI  - Identification of potential emotional and cognitive disturbances in the 3 to 5
      year old child.
AB  - An approach to evaluation using major and minor indicators of emotional and
      cognitive disturbance attempts to overcome the problem of determining the amount
      of importance to be attached to a single observation or item of behavioral
      history.

PMID- 25868184
TI  - The electroencephalogram in clinical pediatrics.
AB  - The electroencephalogram represents an electrical summary of the organizational
      patterns and the total physical-chemical processes taking place in the brain at
      the time of the recording. Itis affected by (1) artifacts secondary to head
      movements, muscle potentials, and eye movements, (2) physiological factors, such
      as state of consciousness, hyperventilation, and maturity of the brain, (3)
      metabolic factors such as temperature, thyroid function, electrolyte changes, and
      numerous other metabolic factors, and (4) drugs. Brain dysfunction also causes
      changes in the electroencephalogram. The electroencephalogram is useful in some,
      but not all, types of brain dysfunction. In general, the electroencephalogram is
      most likely to be abnormal if the underlying disease is acute or ongoing, or if
      the disease is associated with seizures. Focal lesions may appear when none is
      suspected clinically. The electroencephalogram can be an invaluable aid in
      dealing with epilepsy. Petit mal epilepsy cannot be diagnosed without it, and
      infantile spasms are diagnosed with considerably greater certainty if the
      electroencephalogram shows hypsarrhythmia. Patients with seizures which appear to
      be generalized may have an electroencephalogram with focal abnormalities; this
      may be the only clue that a focal lesion exists. Psychomotor epilepsy is
      sometimes difficult to differentiate from sociopathic behavior, and the
      electroencephalogram can be helpful. The electroencephalogram is less useful in
      chronic static conditions such as mental retardation, minimal cerebral
      dysfunction, or behavior disorders, unless there is associated epilepsy or
      ongoing brain pathology. More recently, the electroencephalogram has been used to
      estimate gestational age with reasonable accuracy. With the aid of a computer,
      responses to auditory and visual stimuli have been recorded on the
      electroencephalogram. These techniques, although not in general use at the
      present time, hold considerable promise for the future. They mark the beginnings
      of a new dimension in using the electroencephalogram as a tool in helping the
      clinician evaluate and understand brain development, and in helping him recognize
      early signs of disease in the developing brain.

PMID- 25868185
TI  - Diagnosis of metabolic disease.
AB  - Use of sophisticated diagnostic procedures for the ever-growing list of metabolic
      disorders can be reserved for relatively few cases if simple screening procedures
      are employed in the presence of certain specific clinical signs.

PMID- 25868186
TI  - The cytogenetics laboratory in pediatrics.
AB  - This discussion has attempted to define the role of the cytogenetics laboratory
      in pediatrics and to identify the indications for the major techniques employed
      with emphasis on their usefulness and limitations. When one considers that 1 of
      150 to 175 live births has a chromosomal aberration, the need for accurate
      diagnosis and reliable genetic counselling is apparent. A chromosome analysis
      should be closely correlated and coordinated with the clinical evaluation of the
      patient so that meaningful genetic counselling can be undertaken. The combined
      efforts of the clinician and the cytogenetics laboratory are necessary to
      accomplish the objective.

PMID- 25868187
TI  - Diagnostic needle aspiration in pediatric practice. With special reference to
      lungs, middle ear, urinary bladder, and amniotic cavity.
AB  - Effective antibiotics are now available for most of the common bacterial
      infections. However, with few exceptions they are limited in their spectrum of
      activity and some have significant toxicity. In order to provide rational
      therapy, the physician must have knowledge of the infecting organism. The
      pediatrician is at a particular disadvantage in obtaining specific etiologic
      information since his young patient is often unable to cooperate or volunteer
      materials. In the critically ill child, every effort should be made to obtain
      material from blood and from the focus of infection. Indirect cultures such as
      those of materials from the nose and throat frequently yield confusing results as
      to the etiology of lower respiratory tract infection and of otitis media. Needle
      aspiration of material from the infected focus provides material directly
      pertinent to the etiologic agent for immediate and definitive diagnosis. Lung
      punctures and aspiration of middle ear fluids and bladder urine are discussed as
      examples of useful application of the techniques of needle aspiration. The
      pediatrician should become familiar with these techniques and use them where
      applicable.

PMID- 25868188
TI  - Laboratory diagnosis of urinary tract infection.
AB  - Practical considerations in the timing and method of urine collections, and a
      discussion of useful screening methods for bacteria in urine.

PMID- 25868189
TI  - Urinalysis and its clinical interpretation.
AB  - The importance of changes in urine concentration, acidification, protein, and
      sediment; findings at urinalysis in several common renal diseases of children.

PMID- 25868190
TI  - Laboratory tests in the analysis of states of dehydration.
AB  - In an otherwise healthy child with acute dehydration known to be due to diarrhea
      or vomiting, the amount of deficit can best be estimated by accurate weight.
      Total serum protein and hematocrit provide a rough estimate of reduction in
      circulating blood volume, but calculation from these data will usually
      underestimate the deficit. Determination of urea nitrogen concentration helps to
      detect reduced glomerular filtration rate. Acid-base disturbances, most commonly
      metabolic acidosis, are detected by measuring pH and CO2 content (or base
      excess). Blood glucose should be measured to rule out diabetes mellitus, even in
      the absence of a suggestive history. Determination of potassium in serum is most
      important in the diagnosis of adrenal or renal insufficiency and in the post
      acidotic phase after dehydration. Osmolality of body fluids is estimated by
      measuring [Na+]. Since osmolality of body fluids is normally maintained at the
      expense of fluid volume by the kidney and the hormones governing renal excretion
      of water and sodium, abnormal osmolality indicates a serious condition which has
      to be interpreted with the help of clinical data. In cases of abnormal renal
      function or of abnormal losses, as with removal of gastrointestinal fluids by
      suction, or excessive and prolonged diarrhea, measuring volume and composition of
      excreta may be essential. Because of cumulative deficits, patients with prolonged
      losses or inability to regulate oral intake by thirst cannot be treated without
      continual careful interpretation of the reports from a good laboratory.

PMID- 25868191
TI  - Evaluation of pulmonary function in children.
AB  - Pulmonary function tests determine the type of impairment in many pulmonary,
      neuromuscular, metabolic, and cardiac disorders, and in this way they allow for
      rational treatment.

PMID- 25868192
TI  - Skin testing.
AB  - Skin testing can be a helpful technique epidemiologically and diagnostically,
      provided that its limitations and liabilities are kept in mind. (1) A positive
      skin test, at best, is only a reflection of exposure to the antigen at sometime
      in the past. A negative skin test does not rule out infection. (2) Delayed
      hypersensitivity can be altered by intercurrent infections such as viral diseases
      or vaccines, overwhelming infection producing anergy, intrinsic immunologic
      breakdown, or exogenous causes such as medications. (3) Most antigens utilized
      for skin testing are impure extracts and, therefore, lack specificity. (4)
      Correct interpretation and administration of skin tests requires considerable
      experience and expertise. (5) They require two visits for the patient. Seldom
      should delayed hypersensitivity reactions of cellular immunity as we know them
      today be used as diagnostic tests. Their major contributions should be as an
      epidemiologic tool.

PMID- 25868193
TI  - Diagnosis of disorders of sexual maturation.
AB  - A review of normal pubertal development with recent statistical findings on the
      timing of the events of puberty precedes a discussion of useful laboratory tests
      that measure hormones and their application to the differential diagnosis of
      disorders of sexual maturation.

PMID- 25868194
TI  - Eye testing in children.
AB  - Tests that the pediatrician can perform include vision testing, external
      examination, motility tests, and funduscopic examination; more complete
      evaluations as described are in the province of the ophthalmologist.

PMID- 25868195
TI  - [The journal "Masui", the history of our department and a detached endotracheal
      cuff].

PMID- 25868196
TI  - [Perspectives of research and publication by Japanese anesthesiologists: preface
      and comments].
AB  - Quality of Japanese research has risen and studies are now routinely published in
      international journals. Nevertheless, the number of studies reported by Japanese
      anesthesiologists is rapidly decreasing. Greater clinical workload, increased
      rules for carrying out clinical research and publication, and reported incidents
      of scientific fraud might have been the cause. In this issue, 6 authors from
      Japanese Society of Anesthesiologists and editors of anesthesia journals analyze
      the current state of research activity by Japanese anesthesiologists and indicate
      some practical solutions to increase research activity.

PMID- 25868197
TI  - [Why should clinicians be engaged in research and publication?].
AB  - Why should clinicians be engaged in research and publication? The reason is that
      they have to deliver comprehensive medical care for patients. Clinicians endeavor
      to improve their clinical skills by learning updated medical knowledge and new
      techniques in order to save lives. By taking part in research and publications,
      clinicians are able to contribute actively to the progress in medicine contrary
      to passive involvement in it without research and publications. Mission of
      Japanese Society of Anesthesiologists (JSA), clearly mention that JSA aims to
      advance high quality research and developing new methods in medicine. JSA also
      necessitates, as a minimum requirement for Board Certified Anesthesiologists,
      presentations in annual meeting of JSA or related society meetings and also
      publications in Journal of Anesthesia, an official journal of JSA, or other
      related anesthesia journals. By experiencing research and publications,
      clinicians can obtain knowledge, skills as well as attitudes, which are also
      useful in everyday clinical work, such as logical way of thinking, how to write
      papers to be understood, tolerance to peer review and objective evaluation, and
      maintaining spirit of enterprise in their career.

PMID- 25868198
TI  - [Past contributions to anesthesiology by Japanese anesthesiologists].
AB  - This article describes the first events of general anesthesia in the world by
      Tokumei Takamine in 1698 and Seishu Hanaoka in 1804, the establishment of
      anesthesiology in Japan including the meaning of a scientific society, the
      establishment of Japanese Society of Anesthesiologist and Department of
      Anesthesiology at University of Tokyo, past contributions to anesthesiology by
      Japanese anesthesiologists, and contributions to anesthesiology by Journal of
      Anesthesia and the Japanese Journal of Anesthesiology.

PMID- 25868199
TI  - [The present crisis of the publication activity in anesthesia research in Japan
      and its countermeasure].
AB  - In Japan, a reduction in the number of qualified anesthesiologists has become
      apparent particularly in local university hospitals since the introduction of a
      new postgraduate clinical training system in 2004. In addition, our younger
      generation seems to desire the qualification as an anesthesiologists but not the
      research degree of Doctor of Medicine. As a consequence of high clinical workload
      and a relative lack of interest in research degrees, the publication of
      anesthesia research papers from Japan is progressively declining. In addition,
      the issue of data fabrication in randomized controlled clinical trials by Fujii
      had a negative impact on the motivation within our specialty to perform research
      and may consequently decrease research publications in Japan. If we do not engage
      in anesthesia research activities, it is really possible that our colleagues and
      patients may view us simply as technicians in near future. In the extreme case a
      medical degree may no longer be required for anesthesiologists. However, once we
      were in that kind of position and situation the restoration would be difficult.
      To take countermeasure against this decline in anesthesia research activity, I
      would like to present proposals as follows. Japanese Society of Anesthesiologists
      (JSA) and each educational institution should desperately emdeavour to encourage
      anesthesiologists to enter graduate school of medicine, develop environment for
      continuation in employment of female anesthetists during pregnancy and parenting
      and to perform planning and implementation of JSA initiated research projects
      educating young anesthesiologist for English article writing and medical ethics.
      Moreover, each anesthesiologist must deeply recognize the present crisis of
      anesthesia research activity in Japan, and then do what should be done now.

PMID- 25868200
TI  - [How to establish and organize research activities].
AB  - The goal of this article is to introduce how to establish and organize research
      activities. There are many questions to be answered to make our clinical levels
      higher and more sophisticated, and some of them may also trigger research
      activities. We have two options, clinical study and basic research, and
      combination of these two methods is an ideal way to find answers to these
      questions. Also, cutting edge methodologies often result in some breakthroughs in
      our research field. Collaboration with experts is helpful for application of
      these new methodologies, and it facilitates establishing network of researchers.
      Finally, based on results of many excellent studies (both basic and clinical), we
      design large scale randomized clinical trials, to verify whether these research
      products contribute to improvement in our clinical activity. Excellent results
      give some hints to a next series of studies, and in this context, reviewing and
      updating the achievements are also important. Organizing study groups facilitates
      these activities, and the Japanese Society of Anesthesiologists has recently
      started a project to activate research activity.

PMID- 25868201
TI  - [Required matters in the study enforcement and the publication].
AB  - We must confirm "instructions for authors" in a medical journal before we submit
      a manuscript to the journal. Human studies must conform to ethical standards, and
      be approved by the appropriate Institutional Review Board (IRB). Most
      "instruction for authors" require to obey "WMA Declaration of Helsinki-Ethical
      Principles for Medical Research Involving Human Subjects", "Uniform requirements
      for manuscripts submitted to biomedical journals: Writing and editing for
      biomedical publication" etc. The editors of journal are concerned about
      appropriate IRB review and informed consent. Lack of appropriate consent or
      documentation may be grounds for rejection, and we must understand the necessary
      guidelines before starting a study.

PMID- 25868202
TI  - [Publication of an original work: for self accomplishment as well as for
      advancement of medicine].
AB  - Medical researchers are expected to give back their study results to society (the
      patient). In this context conference presentation and publication in a scientific
      journal are the final stages for the purpose. Therefore, the researchers should
      have knowledge and skill on how to present and write the results logically,
      readably and attractively as a scientific original manuscript Scientific
      misconduct such as fabrication and plagiarism blocks advance of the field and
      deserve social and criminal sanction. Reviewers of the manuscript place a high
      value of novelty of the research and its clinical and scientific impact in
      addition to accuracy and reproducibility of the methodology of the study. They
      provide constructive suggestions for improving it as experts of the field. The
      authors should read their comments carefully and communicate with them
      effectively. Young anesthesiologists are encouraged to experience a sense of
      achievement of publication of their original work.

PMID- 25868203
TI  - [Use of flurbiprofen before emergence from anesthesia relieves pain during
      immediate postoperative period after laparoscopic inguinal hernia repair].
AB  - BACKGROUND: Reduced postoperative pain is considered one of the benefits of
      laparoscopic inguinal hernia repair (LHR). We investigated the need for
      intravenous flurbiprofen axetil (FA) before emergence from anesthesia in patients
      who had undergone LHR. METHODS: Forty adult patients who were prepared for LHR
      were randomly divided into the FA group (FA 1 mg x kg(-1) administered at the end
      of surgery, n = 20) and the control group (no FA administration, n = 20).
      Postoperative pain was evaluated by the Prince Henry Pain Score (PHPS) as well as
      by the frequency of on-demand use of nonsteroidal antiinflammatory drugs
      (NSAIDs). RESULTS: The PHPS on arrival at the ward was significantly lower in the
      FA group than the control group. Additionally, none of the patients of the FA
      group required NSAIDs in the first two hours of postoperative period, compared
      with 6 patients (30%) of the control group. However, at 4 hours postoperatively,
      none of the patients of both groups suffered pain at rest and the PHPS was
      similar in the two groups. CONCLUSIONS: Although postoperative pain after LHR is
      mild and disappears rapidly, FA administration before emergence from anesthesia
      is necessary for management of pain during the immediate postoperative period.

PMID- 25868204
TI  - [Examination of the criteria for selecting the size of a cuffed tracheal tube in
      children].
AB  - BACKGROUND: This paper examined the criteria for selecting Mallinckrodt Hi
      Contour pediatric cuffed tracheal tubes. METHODS: Different age groups are
      generally treated with tubes of the following internal diameters (mm): 0 to 8
      months: 3.0; 8 to 18 months: 3.5; 18 to 36 months: 4.0; and 3 to 5 years: 4.5.
      When it was difficult to intubate, or there was no leak at an airway pressure of
      25 cm H2O, the tube size was regarded as excessively large, and the size was
      reduced. In contrast, when there was a massive air leak, interfering with
      ventilation, the tube size was increased. RESULTS: Replacement was not necessary
      in 94% of those treated with a 3.0-mm tube, 89% of those treated with a 3.5-mm
      tube, 94% of those treated with a 4.0-mm tube, or 97% of those treated with a 4.5
      mm tube. The overall incidence of complications was 4%. CONCLUSIONS: Based on
      these criteria, tube replacement was not necessary in 93% of pediatric patients.

PMID- 25868205
TI  - [Anesthetic management of patients with placenta previa accreta for cesarean
      section: a 7-year single-center experience].
AB  - BACKGROUND: Anesthetic management for cesarean section of patients with placenta
      previa accreta is challenging. The aim of this retrospective study was to review
      past placenta previa accreta cases in our hospital to propose a better strategy
      for anesthetic management for this difficult condition. METHODS: Cases of
      placenta previa accreta were identified in our anesthesia database. The
      diagnosis, surgical procedure, amount of blood loss and anesthetic management
      were reviewed. RESULTS: Eight cases of placenta previa accreta were identified.
      Four of the eight cases underwent stepwise treatment, and in one of the four
      cases, intra-aortic balloon occlusion (IABO) was performed. The amount of blood
      loss in the four cases ranged from 840 to 1,150 ml. The remaining four cases
      underwent cesarean hysterectomy. The amount of blood loss in the four cases
      ranged from 2,400 to 5,200 ml. Neuraxial anesthesia alone was planned in four
      cases, but in two of which anesthesia was converted to general anesthesia due to
      massive bleeding. CONCLUSIONS: The present retrospective study showed that
      stepwise treatment and using IABO could be an effective aid for management of
      plasenta previa accreta. It is necessary to compare the effectiveness of IABO
      with that of common iliac artery occlusion in reducing the amount of blood loss.

PMID- 25868206
TI  - [Ultrasoud-guided paravenous approach for saphenous nerve block in ankle
      surgery].
AB  - BACKGROUND: Blocking conduction in the saphenous nerve is important in providing
      surgical anesthesia of the lower leg. The aim of this retrospective study was to
      determine the efficacy of ultrasound-guided paravenous approach for saphenous
      nerve block. METHODS: Twenty-eight patients underwent ankle surgery after
      saphenous nerve block using ultrasoud-guided paravenous approach below the knee
      combined with sciatic nerve block under general anesthesia. Sensory blockade was
      evaluated at the upper part of the leg as compared with the contralateral leg.
      RESULTS: Twenty four patients (85%) had sensory blockade on the day of the
      surgery. Six patients (21%) had sensory blockade the day after surgery.
      CONCLUSIONS: Paravenous approach for saphenous nerve block may be effective
      particularly with limited resources.

PMID- 25868207
TI  - [Delayed emergence from general anesthesia in a dementia patient with Lewy
      bodies].
AB  - A 73-year-old man (164cm height 51 kg body weight) with a history of Parkinson's
      disease and dementia was scheduled for a cervical lymph node biopsy under general
      anesthesia. We induced anesthesia with thiamylal and fentanyl, and maintained
      with sevoflurane and remifentanil without any incident. The patient did not
      emerge from anesthesia after the surgery. He developed coma and did not respond
      to painful stimuli. However, his breathing was spontaneous with stable
      hemodynamics. Although naloxone was given, he was still comatose. His clinical
      neurological findings showed no organic abnormalities. Forty minutes after the
      surgery, he suddenly woke up and followed instructions. We learned that
      previously he had been diagnosed with dementia with Lewy bodies.

PMID- 25868208
TI  - [Anesthetic management for a patient with chronic expanding hematoma of the
      thorax associated with respiratory failure].
AB  - Chronic expanding hematoma (CEH) of the thorax is an intractable disease which
      induces long-standing growing hematoma after tuberculosis or thoracic surgery. It
      causes respiratory failure and heart failure by compressing the mediastinum. A 68
      year-old man with a history of tuberculosis during childhood had suffered from
      progressive exertional dyspnea for 20 years. Because a huge hematoma occupying
      whole right thoracic cavity compressed the heart and the trachea to the left, he
      was scheduled for extrapleural pneumonectomy. Bronchial arterial embolization was
      performed preoperatively to prevent hemoptysis and reduce intraoperative blood
      loss. There was no problem in the airway management using a double lumen
      endotracheal tube. However, severe hypotension and a decrease in cardiac index
      were observed due to excessive bleeding, leading to total blood loss of 11,000 g.
      In addition, surgical manipulation caused abrupt severe hypotension. Monitoring
      of arterial pressure-based cardiac output and deep body temperature was useful
      for the hemodynamic management during the operation. The successful postoperative
      course resulted in remarkable improvement of Huge-Jones dyspnea criteria from IV
      to II. In the anesthetic management of CEH precautions should be taken against
      the excessive intraoperative bleeding and abrupt hemodynamic changes.

PMID- 25868209
TI  - [Craniotomy in a pediatric patient complicated with insufficiently controlled
      diabetes mellitus: intraoperative management with remifentanil and an electrolyte
      containing glucose solution].
AB  - An 8-year-old girl of Type 1 diabetes mellitus on insulin therapy, was surgically
      treated for brain cavernous hemangioma. Since the hemangioma gradually became
      larger, the medical team including anesthesiologists, neurosurgeons, and
      pediatricians discussed and decided to perform craniotomy. Preoperative blood
      sugar level was around 40 to 300 mg x dl(-1) and appeared poorly controlled.
      During the surgery, opioid-based anesthesia and 1.3% glucose infusion were given
      to the patient to avoid surgical stress-induced hyperglycemia and to avoid
      starvation. Intraoperative blood sugar levels were maintained exactly at 100 to
      120 mg x dl(-1) without insulin medication, and cortisol levels were below the
      limit of detection. Postoperative sugar level was difficult to control at the
      preoperative level Tumor was completely removed and the patient was discharged
      without any neurological sequelae. This report suggests that sufficient analgesia
      with remifen tanil and appropriate glucose infusion may be useful for the
      metabolic management not only in patients without diabetes but also in those with
      diabetes.

PMID- 25868210
TI  - [A case of impossible ventilation after induction of anesthesia in a patient with
      massive nasal bleeding].
AB  - We report a case of impossible ventilation in a patient with severe nasal
      bleeding. A 47-year-old man with intractable nasal bleeding was scheduled for
      emergent hemostasis under general anesthesia. He also had alcohol-related
      cirrhosis and was highly obese (165 cm, 93 kg). Although he sufficiently fasted
      and did not experience nausea in the supine position, we planned crash intubation
      in the head-elevated position with the Pentax-AWS Airwayscope (AWS) in order to
      avoid vomiting after induction of anesthesia. After fentanyl, propofol, and
      rocuronium administration, the patient vomited a large amount of blood, which led
      to a deterioration of SpO2. Mask ventilatidn was impossible even after oral
      suctioning. We intubated the trachea with the Macintosh laryngoscope and
      suctioned blood from the trachea; SpO2 gradually improved and the trachea was
      washed with a large amount of normal saline. The patient was transferred to the
      intensive care unit and extubated uneventfully on day 3 postoperatively.

PMID- 25868211
TI  - [Successful sedation with landiolol and dexmedetomidine during spinal anesthesia
      in a patient with active dementia].
AB  - We report a successful case of sedation during spinal anesthesia using continuous
      administration of landiolol and dexmedetomidine in a patient with severe
      dementia. An 86-year-old man weighing 63 kg with severe dementia and chronic
      obstructive pulmonary disease was scheduled for emergent open reduction of
      fracture under spinal anesthesia. On admission, he presented with delirium as a
      result of pain and environmental change. He also suffered from herpes zoster
      infection and we decided to perform the operation under spina anesthesia. To
      alleviate his anxiety and state of panic we continuously administered landiolol
      10 MUg x g kg(-1). min(-1) and dexmedetomidine 0.4 MUg x kg(-1) x hr(-1). After
      10 minutes, he was sedated and agreed to undergo spinal anesthesia. Spinal
      anesthesia was successful with isobaric bupivacaine 3.0 mI. The patient showed no
      untoward behavior during anesthesia and the operation.

PMID- 25868212
TI  - [A multicenter survey of pediatric endotracheal tube management].
AB  - BACKGROUND: The goal of this multicenter survey was to examine the variety of
      pediatric endotracheal tube (PETT) management methods utilized by
      anesthesiologists. METHODS: A postal survey for PETT management methods was
      performed among anesthesiologists at Kyoto Prefectural University of Medicine and
      its affiliated hospitals. RESULTS: Age was the primary criteria for PETT size
      selection, followed by height and weight, while the surgical procedure was the
      primary criteria for PETT type selection, followed by age and then weight. Cuffed
      PETTs were routinely used for more than 70% of their patients by 57.1% of
      respondents; however, 55.7% of respondents had no criteria clearly defining when
      and how to inflate the cuff. Strategies for airway complications, including post
      extubation stridor, vary amongst anesthesiologists. CONCLUSIONS: The present
      study revealed that practice of PETT management depends on anesthesiologists.
      PETT management should be sophisticated with wide use of cuffed PETTs.

PMID- 25868213
TI  - The benefits of taking a breath. .

PMID- 25868214
TI  - Holistic approach to dental education.

PMID- 25868215
TI  - Risk assessment misuse.

PMID- 25868216
TI  - Interprofessional collaboration: opportunity for dentists to reinvent themselves
      as oral physicians.

PMID- 25868217
TI  - Dental school disconnect.

PMID- 25868218
TI  - Code of ethics?

PMID- 25868219
TI  - The world is coming apart.

PMID- 25868220
TI  - The impact of student research in California dental schools.

PMID- 25868221
TI  - Recall compliance and incidence of dental caries among underserved children.
AB  - Regular dental recall intervals are widely recommended by dentists in the U.S. to
      prevent caries and improve periodontal health. However, there is some debate on
      whether or not compliance with six-month or more frequent recall intervals
      results in reduced incidence of dental caries. This study examines whether
      compliance with regular recall and receipt of cleanings, exams and patient
      education reduces rates of new decay in underserved children and finds a positive
      impact.

PMID- 25868222
TI  - Dye leakage and modification of fast-setting mineral trioxide aggregate.
AB  - The objective of this investigation was to determine and decrease dye leakage of
      fast-setting mineral trioxide aggregate (FSMTA). Specimens using differing
      setting times or concentrations of calcium sulfate modified FSMTA were assessed
      for dye penetration. Based on the results, no statistical difference was found in
      the dye leakage of FSMTA compared with regular mineral trioxide aggregate (MTA).
      The addition of 10 percent calcium sulfate resulted in a statistical reduction in
      dye leakage compared to both unmodified FSMTA and regular MTA.

PMID- 25868223
TI  - The changing role of HIV-associated oral candidiasis in the era of HAART.
AB  - Oral candidiasis is the most common fungal opportunistic infection to affect the
      oral cavity among HIV patients. The advent of highly active antiretroviral
      therapy (HAART) has changed the epidemiology of candidiasis, with many studies
      reporting a decrease in prevalence. However, some studies report rare cases of
      increased prevalence. This systematic review clarifies the role of oral
      candidiasis in the HAART era as a marker of immune status and successful therapy
      for the HIV-infected population.

PMID- 25868224
TI  - Mannose-specific lectins that inhibit HIV infection bind nonspecifically to HIV
      Env-expressing cells.
AB  - An approach to curing HIV/AIDS is to specifically kill all infected cells.
      Because the lectins, Hippeastrum hybrid agglutinin (HHA) and Galanthus nivalis
      agglutinin (GNA), are potent inhibitors of HIV infection and bind the
      oligomannans on the HIV Env protein, we hypothesized that they would bind
      specifically to cells expressing the HIV Env protein on their plasma membrane.
      Flow cytometry experiments indicated, however, that these lectins bind
      equivalently to both Env-expressing and control cells without Env.

PMID- 25868225
TI  - Straight-ahead facts on wage and hour rules.

PMID- 25868226
TI  - Blood-borne pathogens Q&A.

PMID- 25868227
TI  - [Effect of stimulating pulse width on the threshold of electrically evoked
      compound action potential].
AB  - This paper discusses the relationship between stimulating pulse width and the
      threshold of electrically evoked compound action potential (ECAP). Firstly, the
      rheobase and chronaxy from strength-duration curve of nerve fiber was computed
      using the shepherd's experiment results. Secondly, based on the relationship
      between ECAP and the action potential of nerve fiber, a mathematical expression
      to describe the relationship between stimulating pulse width and ECAP threshold
      was proposed. Thirdly, the parameters were obtained and the feasibility was
      proved to the expression with the results of experiment using guinea pigs.
      Research result showed that with ECAP compared to the action potential of nerve
      fiber, their threshold function relationship with stimulating pulse width was
      similar, and rheobase from the former was an order smaller in the magnitude than
      the latter, but the chronaxy was close to each other. These findings may provide
      meaningful guidance to clinical ECAP measurement and studying speech processing
      strategies of cochlear implant.

PMID- 25868228
TI  - [Effect of fast capacitance compensation method on improving the action potential
      firing accuracy of nerve cell].
AB  - Patch-clamp is used to study all sorts of ionic channels and their regulations
      with measuring pA current of cell ionic channel, but the fast capacitance (C
      fast) compensation and slow capacitance (C-slow) compensation transient currents
      are caused by measuring objects and measuring instruments themselves which will
      change the properties of action potentials. The present paper firstly discusses
      the C-Fast transient currents affecting membrane capacitance and membrane
      potential, and then draws a conclusion that the changes of membrane potential
      affect the properties of action potential through analyzing the changes of
      membrane potential in H-H model. Based on this conclusion, we discuss the
      influence mechanisms mainly through the analysis of traditional C-fast
      compensation errors, and focus discussion on the shape of electrode capacitance
      affecting C-fast. This method can not only improve the compensation speed
      greatly, but also improve the compensation precision from the electrode shape as
      much as possible.

PMID- 25868229
TI  - [Research on the methods for electroencephalogram feature extraction based on
      blind source separation].
AB  - In the present investigation, we studied four methods of blind source
      separation/independent component analysis (BSS/ICA), AMUSE, SOBI, JADE, and
      FastICA. We did the feature extraction of electroencephalogram (EEG) signals of
      brain computer interface (BCI) for classifying spontaneous mental activities,
      which contained four mental tasks including imagination of left hand, right hand,
      foot and tongue movement. Different methods of extract physiological components
      were studied and achieved good performance. Then, three combined methods of SOBI
      and FastICA for extraction of EEG features of motor imagery were proposed. The
      results showed that combining of SOBI and ICA could not only reduce various
      artifacts and noise but also localize useful source and improve accuracy of BCI.
      It would improve further study of physiological mechanisms of motor imagery.

PMID- 25868230
TI  - [Research on the methods for inter-class distinctive feature selection for
      leucocyte recognition based on attribute hierarchical relationship].
AB  - To increase efficiency of automated leucocyte pattern recognition using lower
      feature dimensions, a novel inter-class distinctive feature selection method for
      chromatic leucocyte images was proposed based on attribute hierarchical
      relationship. According to the attribute constraints in formal concept analysis,
      we established a knowledge representation and discovery method based on the
      hierarchical optimal diagram by defining attribute value and visual
      representation of optimized hierarchical relationship. It was applied to human
      peripheral blood leucocytes classification and 12 distinctive attributes were
      simplified from 60 inter-class attributes, which contributes significantly to
      reduced feature dimensions and efficient inter-class feature classification.
      Compared with the classical experimental data, the inter-class distinctive
      feature selection method based on hierarchical optimal diagram was proved to be
      usable and effective for six leucocyte pattern recognition.

PMID- 25868231
TI  - [Research on calculation of the regional cerebral blood volume based on minimum
      mean square error method].
AB  - In this paper, the Fourier transform based minimum mean square error (FT-based
      MMSE) method is used to calculate the regional cerebral blood volume (rCBV) in
      magnetic resonance (MR) perfusion imaging, and the method is improved to handle
      the existing noise in the imaging process. In the experiments with signal-to
      noise ratio (SNR) of 50 dB, the rCBV values were compared with the results using
      MMSE method. The effects of different SNRs on the estimation of rCBV were
      analyzed. The experimental results showed that MMSE was a simple way to filter
      the measurement noise, and could calculate rCBV accurately. Compared with other
      existing methods, the present method is not sensitive to environment, and
      furthermore, it is suitable to deal with the perfusion images acquired from the
      environment with larger SNR.

PMID- 25868232
TI  - [Research of the late positive potential of emotional cognitive reappraisal
      electroencephalogram signal based on OVR-CSP].
AB  - As an important component of the event related potential (ERP), late positive
      potential (LPP) is an ideal component for studying emotion regulation. This study
      was focused on processing and analysing the LPP component of the emotional
      cognitive reappraisal electroencephalogram (EEG) signal. Firstly, we used
      independent component analysis (ICA) algorithm to remove electrooculogram,
      electromyogram and some other artifacts based on 16 subjects' EEG data by using
      EGI 64-channal EEG acquisition system. Secondly, we processed feature extraction
      of the EEG signal at Pz electrode by using one versus the rest common spatial
      patterns (OVR-CSP) algorithm. Finally, the extracted LPP component was analysed
      both in time domain and spatial domain. The results indicated that (1) From the
      perspective of amplitude comparison, the LPP amplitude, which was induced by
      cognitive reappraisal, was much higher than the amplitude under the condition of
      watching neural stimuli, but lower than the amplitude under condition of watching
      negative stimuli; (2) from the perspective of time process, the difference
      between cognitive reappraisal and watching after processing with OVR-CSP
      algorithm was in the process of range between 0.3 s and 1.5 s; but the difference
      between cognitive reappraisal and watching after processing with averaging method
      was during the process between 0.3 s and 1.25 s. The results suggested that OVR
      CSP algorithm could not only accurately extract the LPP component with fewer
      trials compared with averaging method so that it provided a better method for the
      follow-up study of cognitive reappraisal strategy, but also provide
      neurophysiological basis for cognitive reappraisal in emotional regulation.

PMID- 25868233
TI  - [Feature extraction for breast cancer data based on geometric algebra theory and
      feature selection using differential evolution].
AB  - The feature extraction and feature selection are the important issues in pattern
      recognition. Based on the geometric algebra representation of vector, a new
      feature extraction method using blade coefficient of geometric algebra was
      proposed in this study. At the same time, an improved differential evolution (DE)
      feature selection method was proposed to solve the elevated high dimension issue.
      The simple linear discriminant analysis was used as the classifier. The result of
      the 10-fold cross-validation (10 CV) classification of public breast cancer
      biomedical dataset was more than 96% and proved superior to that of the original
      features and traditional feature extraction method.

PMID- 25868234
TI  - [Research on measuring the velocity and displacement of the coxa and knee based
      on video image processing].
AB  - Based on repeated experiments as well as continuous researching and improving, an
      efficient scheme to measure velocity and displacement of the coxa and knee
      movements based on video image processing technique is presented in this paper.
      The scheme performed precise and real-time quantitative measurements of 2D
      velocity or displacement of the coxa and knee using a video camera mounted on one
      side of the healing and training beds. The beds were based on simplified pinhole
      projection model. In addition, we used a special-designed auxiliary calibration
      target, composed by 24 circle points uniformly located on two concentric circles
      and two straight rods which can rotate freely along the concentric center within
      the vertical plane, to do the measurements. Experiments carried out in our
      laboratory showed that the proposed scheme could basically satisfy the
      requirements about precision and processing speed of such kind of system, and
      would be very suitable to be applied to smart evaluation/training and healing
      system for muscles/balance function disability as an advanced and intuitional
      helping method.

PMID- 25868235
TI  - [Application study of optical method in measuring wall thickness of dental
      impression].
AB  - Dental impressions are widely used in the field of oral restoration. The
      materials are used for making impression in oral cavity. In order to measure the
      thickness of impression for reference in clinic, the real impressions are taken
      as the object for studying. Through optical method, charge-coupled device (CCD)
      is used for collecting the grey image of cutting section of the impressions which
      are located in the same plane with steel dividing ruler. According to convert
      relationship between dividing ruler and pixels collecting grey image, the
      thickness of impression specimens can be obtained. The results show that the
      optical method used for measuring thickness is feasible to the task and the
      precision can reach micro dimension. The experiment method and technique can also
      be provided for measuring thickness of similar tissue engineering materials.

PMID- 25868236
TI  - [Development of a computerized three-dimension system for displaying and
      analyzing mandibular helical axis pathways].
AB  - This paper is aimed to develop a computerized three dimensional system for
      displaying and analyzing mandibular helical axis pathways. Mandibular movements
      were recorded using a six-degrees-of-freedom ultrasonic jaw movement recording
      device. The three-dimensional digital models of the midface and the mandible were
      reconstructed and segmented from CT skull images. The digital models were then
      transformed to the coordinate system of mandibular motion data by using an
      optical measuring system. The system was programmed on the base of the
      Visualization ToolKit and Open Scene Graphics Library. According to the motion
      data, transformation matrices were calculated to simulate mandibular movements.
      Meanwhile, mandibular helical axis pathways were calculated and displayed three
      dimensionally by means of an eigenvalues method. The following parameters of
      mandibular helical axis were calculated: the rotation around instantaneous
      helical axis, the translation along it, its spatial orientation, its position and
      distance relative to any special reference point. These parameters could be
      exported to describe comprehensively the whole mandiblular movements. It could be
      concluded that our system would contribute to the study of mandiblular helical
      axis pathways.

PMID- 25868237
TI  - [Development and validation of a CO-T1 three-dimensional finite element model of
      a healthy person under physiologic loads].
AB  - A comprehensive, geometrically accurate, nonlinear C0-T1 three-dimensional finite
      element (FE) model was developed for the biomechanical study of human cervical
      spine and related disorders. The model was developed with anatomic detail from
      the computed tomography (CT) images of a 46-year-old female healthy volunteer,
      and applied the finite element model processing softwares such as MIMICS13.1,
      Hypermesh11.0, Abaqus 6.12-1, etc., for developing, preprocessing, calculating
      and analysing sequentially. The stress concentration region and the range of
      motion (ROM) of each vertebral level under axial rotation, flexion, extension,
      and lateral bending under physiologic static loadings were observed and recorded.
      The model was proven reliable, which was validated with the range of motion in
      previous published literatures. The model predicted the front and side parts of
      the foramen magnum and contralateral pedicle and facet was the stress
      concentration region under physiological loads of the upper spine and the lower
      spine, respectively. The development of this comprehensive, geometrically
      accurate, nonlinear cervical spine FE model could provide an ideal platform for
      theoretical biomechanical study of human cervical spine and related disorders.

PMID- 25868238
TI  - [A modeling method for human standing balance system based on T-S fuzzy
      identification].
AB  - In order to develop safe training intensity and training methods for the passive
      balance rehabilitation train- ing system, we propose in this paper a mathematical
      model for human standing balance adjustment based on T-S fuzzy identification
      method. This model takes the acceleration of a multidimensional motion platform
      as its inputs, and human joint angles as its outputs. We used the artificial bee
      colony optimization algorithm to improve fuzzy C--means clustering algorithm,
      which enhanced the efficiency of the identification for antecedent parameters.
      Through some experiments, the data of 9 testees were collected, which were used
      for model training and model results validation. With the mean square error and
      cross-correlation between the simulation data and measured data, we concluded
      that the model was accurate and reasonable.

PMID- 25868239
TI  - [Dynamic modeling and simulating of squatting-standing action of human body].
AB  - It is very difficult for stroke patients to complete the action of squatting
      standing because their equilibrium function ability has been seriously declined.
      It was necessary, therefore, to do a deep research on the action of human
      squatting-standing and to set up an accurate model and simulation. In our
      modeling research, the movements of upper limbs and head was neglected, and a
      seven-segment model was developed to establish the coordinate system of human
      squatting-standing action. It calculated the knee joint moment and hip joint
      moment during squatting and standing by utilizing Lagrange method, and then
      simulated this mathematical model by utilizing Matlab. Geometric model of human
      squatting-standing was developed and simulated in ADAMS which proved that the
      established Lagrange model was reasonable. It would also provide significant
      theoretical references for further study and development of squatting-standing
      rehabilitation training equipment.

PMID- 25868240
TI  - [Finite element analysis of temperature field of retina by electrical stimulation
      with microelectrode array].
AB  - We studied the influence of electrode array parameters on temperature
      distribution to the retina during the use of retinal prosthesis in order to avoid
      thermal damage to retina caused by long-term electrical stimulation. Based on
      real epiretinal prosthesis, a three-dimensional model of electrical stimulation
      for retina with 4 X 4 microelectrode array had been established using the finite
      element software (COMSOL Multiphysics). The steady-state temperature field of
      electrical stimulation of the retina was calculated, and the effects of the
      electrode parameters such as the distance between the electrode contacts, the
      materials and area of the electrode contact on temperature field were considered.
      The maximum increase in the retina steady temperature was about 0. 004 degrees C
      with practical stimulation current. When the distance between the electrode
      contacts was changed from 130 microm to 520 microm, the temperature was reduced
      by about 0.006 microC. When the contact radius was doubled from 130 microm to 260
      microm, the temperature decrease was about 0.005 degrees C. It was shown that
      there were little temperature changes in the retina with a 4 x 4 epiretinal
      microelectrode array, reflecting the safety of electrical stimulation. It was
      also shown that the maximum temperature in the retina decreased with increasing
      the distance between the electrode contacts, as well as increasing the area of
      electrode contact. However, the change of the maximum temperature was very small
      when the distance became larger than the diameter of electrode contact. There was
      no significant difference in the effects of temperature increase among the
      different electrode materials. Rational selection of the distance between the
      electrode contacts and their area in electrode design can reduce the temperature
      rise induced by electrical stimulation.

PMID- 25868241
TI  - [Numerical assessment of impeller features of centrifugal blood pump based on
      fast hemolysis approximation model].
AB  - The impeller profile, which is one of the most important factors, determines the
      creation of shear stress which leads to blood hemolysis in the internal flow of
      centrifugal blood pump. The investigation of the internal flow field in
      centrifugal blood pump and the estimation of the hemolysis within different
      impeller profiles will provide information to improve the performance of
      centrifugal blood pump. The SST kappa-omega with low Reynolds correction was used
      in our laboratory to study the internal flow fields for four kinds of impellers
      of centrifugal blood pump. The flow fields included distributions of pressure
      field, velocity field and shear stress field. In addition, a fast numerical
      hemolysis approximation was adopted to calculate the normalized index of
      hemolysis (NIH). The results indicated that the pressure field distribution in
      all kinds of blood pump were reasonable, but for the log spiral impeller pump,
      the vortex and backflow were much lower than those of the other pumps, and the
      high shear stress zone was just about 0.004%, and the NIH was 0.0089.

PMID- 25868242
TI  - [Biomechanical analysis of different ProDisc-C arthroplasty design parameters
      after implanted: a numerical sensitivity study based on finite element method].
AB  - This study was aimed to estimate the effect of different ProDisc-C arthroplasty
      designs after it was implanted to C5-C6 cervicalspine. Finite element (FE) model
      of intact C5-C6 segments including the vertebrae and disc was developed and
      validated. Ball-and-socket artificial disc prosthesis model (ProDisc-C, Synthes)
      was implanted into the validated FE model and the curvature of the ProDisc-C
      prosthesis was varied. All models were loaded with compressed force 74 N and the
      pure moment of 1.8 Nm along flexion-extension and bilateral bending and axial
      torsion separately. The results indicated that the variation in the curvature of
      ball and socket configuration would influence the range of motion in
      flexion/extension, while there were not apparently differences under other
      conditions of loads. The method increasing the curvature will solve the stress
      concentration of the polyethylene, but it will also bring adverse outcomes, such
      as facet joint force increasing and ligament tension increasing. Therefore, the
      design of artificial discs should be considered comprehensively to reserve the
      range of motion as well as to avoid the adverse problems, so as not to affect the
      long-term clinical results.

PMID- 25868243
TI  - [Research on numerical simulation of temperature distribution during transcranial
      tumor therapy with high intensity focused ultrasound].
AB  - Numerical simulation is one of the most significant methods to predict the
      temperature distribution in high-intensity focused ultrasound (HIFU) therapy. In
      this study, the adopted numerical simulation was used based on a transcranial
      ultrasound therapy model taking a human skull as a reference. The approximation
      of the Westervelt formula and the Pennes bio-heat conduction equation were
      applied to the simulation of the transcranial temperature distribution. According
      to the temperature distribution and the Time Reversal theory, the position of the
      treatable focal region was corrected and the hot spot existing in the skull was
      eliminated. Furthermore, the influence of the exposure time, input power and the
      distance between transducer and skull on the temperature distribution was
      analyzed. The results showed that the position of the focal region could be
      corrected and the hot spot was eliminated using the Time Reversal theory without
      affecting the focus. The focal region above 60 degrees C could be formed at the
      superficial tis sue located from the skull of 20 mm using the hot spot
      elimination method and the volume of the focal region increases with the exposure
      time and the input power in a nonlinear form. When the same volume of the focal
      region was obtained, the more power was inputted, the less the exposure time was
      needed. Moreover, the volume of the focal region was influenced by the distance
      between the transducer and the skull.

PMID- 25868244
TI  - [Experimental gait study based on the plantar pressure test for the young
      people].
AB  - Based on force sensing resistor (FSR) sensor, we designed insoles for pressure
      measurement, which were stable and reliable with a simple structure, and easy to
      wear and to do outdoor experiments with. So the insoles could be used for gait
      detection system. The hardware includes plantar pressure sensor array, signal
      conditioning unit and main circuit unit. The software has the function of data
      acquisition, signal processing, feature extraction and classification function.
      We collected 27 groups of gait data of a healthy person based on this system to
      analyze the data and study pressure distribution under various gait features,
      i.e., walking on the flat ground, uphill, downhill, up the stairs, and down the
      stairs. These five gait patterns for pattern recognition and classification by K
      nearest neighbors (KNN) recognition algorithm reached up to 90% accuracy. This
      preliminarily verified the usefulness of the system.

PMID- 25868245
TI  - [Design and validation of synchronous exposure control system of dental cone beam
      CT].
AB  - In the design of oral cone beam CT, cooperation between synergic control of X-ray
      source, real-time acquisition of flat detector and motion of mechanical structure
      affects the CT image quality. Based on the full analysis of the flat detector's
      timing signal characteristics, this research was carried out with microprocessor
      controller (MCU), complex programmable logic device (CPLD), and light couplings
      to design and realize synchronous exposure control system. To evaluate whether
      the design of the synchronous exposure control system in this project could reach
      the required imaging accuracy, we employed the projected images in the system to
      analyze its stability, linear consistency, signal to noise ratio and precede the
      FDK construction.

PMID- 25868246
TI  - [Study on a new urine analysis core module based on semi-reflection mirror].
AB  - A new urine analysis core module based on high performance 32-bit microprocessor
      and high precision color sensor was presented. A novel optical structure and a
      specific circuit were applied to improve measurement precision and temperature
      was used to compensate for results in this core module. The information of urine
      test peice, such as all original data and color RGB value, reflectivity, semi
      quantitative level, etc. can be output. The results showed that the measuring
      precision was about 95% or above with ideal stability and reliability using this
      presented core module, which can be conveniently applied in various urine
      analyzers, and can greatly decrease the cost of urine analyzers in development
      and production.

PMID- 25868247
TI  - [Design of the temperature control system for the thermostatic medical infusion
      pump].
AB  - In surgery operations, wound should be cleaned with warm sterilized saline
      solution. In order to reach rapidly warming the washing solution from the room
      temperature during the surgery, we designed a thermostatic medical infusion pump.
      The present paper mainly presents researches on the two temperature control
      methods in the standby mode and in the flushing mode of the system. In the
      standby mode, the traditional proportional-integral-derivative (PID) control
      algorithm was adopted. In the flushing mode, dynamic characteristics of the
      system was changed in real time, which made the thermostatic control process more
      complex, and the fitted control function combined with the PID control algorithm
      was adopted in this mode. The temperature control parameters were adjusted in
      real time according to the initial temperature and the flow rate of the washing
      solution to obtain a constant temperature of the washing solution, no matter how
      the initial temperature and the flow rate are changed. The experiment results
      showed that this kind of control system performed well with a high accuracy.

PMID- 25868248
TI  - [Mechanical properties and biological evaluation of buffalo horn material].
AB  - Mechanical properties and biological evaluation of buffalo horn material were
      examined in this study. The effects of sampling position of buffalo horn on
      mechanical properties were investigated with uniaxial tension and micron
      indentation tests. Meanwhile, the variation of element contents in different
      parts of buffalo horn was determined with elemental analysis, and the
      microstructure of the horn was measured with scanning electron microscopy. In
      addition, biological evaluation of buffalo horn was studied with hemolytic test,
      erythrocyte morphology, platelet and erythrocyte count, and implantation into
      mouse. Results showed that the buffalo horn had good mechanical properties and
      mechanical characteristic values of it gradually increased along with the growth
      direction of the horn, which may be closely related to its microstructure and
      element content of C, N, and S in different parts of the buffalo horn. On the
      other hand, because the buffalo horn does not have toxicity, it therefore does
      not cause hemolysis of erythrocyte and has a good affinity with it. Buffalo horn
      has good histocompatibility but meanwhile it may induce the platelet adhesion and
      aggregation. Even so, it does not continue to rise to induce a large number of
      platelet to aggregate with resulting blood clotting. Therefore, the buffalo horn
      material has been proved to possess good blood compatibility according to the
      preliminary evaluation.

PMID- 25868249
TI  - [Hippocampal neuron damage and cognitive dysfunction of diabetic Wistar rats].
AB  - This study aimed to explore the cognitive dysfunction of and hippocampal neuron
      damage to Wistar rats with STZ-induced diabetes at different morbidity time. All
      Wistar rats in the tests received intraperitoneal injections of streptozotocin
      (STZ; 60 mg/kg) to induce type 1 diabetes. The concentration of blood glucose and
      the body weight were investigated, the cognitive ability of rats was assessed
      using a standardized Y-maze, and the apoptotic neurons in the CA1 of the
      hippocampus were also examined by using the HE staining. While the sickening time
      was prolonged, the blood glucose concentration of the experimental rats increased
      continuously and the body weight decreased. On the 70th day after STZ
      administration, the neuronal loss in the hippocampal CA1 region increased and the
      working errors increased in rats with the diabetes. The results showed that
      Wistar rats could complicate with diabetic encephalopathy in 70 days after
      injection of STZ for inducing the diabetes.

PMID- 25868250
TI  - [CK2beta promotes Pink1/Parkin-mediated MIRO1 degradation].
AB  - PTEN-induced putative kinase 1 (PINK1), a Parkinson's disease (PD)-related
      protein, has two isoforms, the mitochondria-localized full-length isoform PINK1FL
      and the cytoplasm-localized short isoform PINK1-cyto. Studies have suggested that
      PINK1FL can selectively accumulate at the surface of damaged mitochondria and
      cooperate with another Parkinson's Disease-related protein PARKIN to trigger the
      degradation of MIRO1, a mitochondria trafficking regulator. The functions of
      PINK1-cyto are, however, not yet clear. To investigate the functions of PINK1
      cyto, we expressed different proteins in cultured HEK293 cells by transfecting it
      with different plasmids, and detected the protein levels by Western blot after
      expressing for 24 h. We found that in cultured HEK293 cells, PINK1-cyto could
      also cooperate with PARKIN degrade MIRO1 in the presence of CK23, and the
      regulatory subunit of Casein Kinase II. Interestingly, this function of CK2P was
      not dependent on CK2alpha, the catalytic subunit of Casein Kinase II. We also
      found that CK2P could promote the direct interaction between PINK1-cyto and MIRO1
      by immunocoprecipitation analysis. This result suggested that in addition to
      CK2alpha, CK2beta could also form a kinase complex.

PMID- 25868251
TI  - [Research on influence of different syringe types on quality control of syringe
      pump].
AB  - To evaluate the influence of different brands of syringes on performance
      parameters and application quality of syringe pump, we carried out matching
      experiment of infusion/syringe pump analyzer Rigel Multi-Flo, made by ALK Co. in
      Sweden, for 3 different types of syringes to measure the flow rate, occlusion
      alarm pressure, occlusion time and bolus volume of 26 syringe pumps. Data of
      quality control were analyzed with statistical method. The results demonstrated
      that there were significant differences in the flow rate, occlusion alarm
      pressure, occlusion time and bolus volume (P<0. 01) between those of common
      syringes and original syringes. This study points out that the health care
      providers should select compatible syringes for syringe pumps, which provides
      evidence and guidance to assure the reasonable and safe application of syringe
      pumps in clinical practice.

PMID- 25868252
TI  - [Research on expression of somatomedin b domain of proteoglycan 4 and recombinant
      protein aggregation].
AB  - Recombinant protein SMB(PRG4) containing two Somatomedin B domains and a small
      amount of glycosylation of repetitive sequences of proteoglycan 4 was cloned
      according to PGR4 gene polymorphism. Mature purification process was established
      and recombinant protein SMB(PRG4), with high-level expression was purified. By
      using size-exclusion chromatogaraphy and dynamic light scattering, we found that
      the recombinant protein self-aggregate to dimeric form. Structure prediction and
      non-reducing electrophoresis revealed that SMB(PRG4), was a non-covalently bonded
      dimer.

PMID- 25868253
TI  - [Change of pulse transit time during stepwise paced breathing].
AB  - To investigate the effect of stepwise paced breathing (PB) on pulse transit time
      (PTT), we collected physiological signals of electrocardiogram (ECG), respiration
      and arterial pulse wave during a procedure of stepwise PB, which consists of 6
      different breathing rates changing in a protocol of 14.0-12.5-11.0-9.5-8.0-7.0
      breath per minute (BPM), with each breathing rate lasting 3 minutes. Twenty two
      healthy adults involved in this experiment and the change of PTT was analyzed
      during the stepwise PB procedure. In our study, the PTT was measured by
      calculating the time interval from the R-spike of the ECG to the peaks of the
      second derivative of the arterial pulse wave. Ensemble empirical mode
      decomposition (EEMD) was applied to PTT to decompose the signal into different
      intrinsic mode function, and respiratory oscillation and trend component
      (baseline) in PTT were further extracted. It was found that the respiratory
      oscillations in the PTT increased with decreasing of the PB rate, and many of the
      subjects (14 out of 22) showed the phenomena of PTT baseline increasing during
      the stepwise PB procedure. The results indicated that the stepwise PB procedure
      induced a high level of cardiovascular oscillation and produced an accumulative
      effect of PTT baseline increase. As PTT is capable of predicting changes in BP
      over a short period of time, increase of PTT baseline indicates the decrease of
      blood pressure. The experiments showed that the stepwise PB procedure could
      reduce blood pressure for most subjects. For future work, it is necessary to
      develop certain indices differentiating the effectiveness of the stepwise PB
      procedure on the PTT baseline change, and to test the effectiveness of this
      stepwise PB procedure on blood pressure reduction for patients with essential
      hypertension.

PMID- 25868254
TI  - [A Feasibility Study of closing the small bowel with high-frequency welding
      device].
AB  - This study aimed to evaluate the feasibility and effectiveness of closing the
      small bowel in an ex vivo porcine model with high-frequency welding device. A
      total of 100 porcine small bowels were divided into two groups, and then were
      closed with two different methods. The fifty small bowels in experimental group
      were closed by the high-frequency welding device, and the other fifty small
      bowels in comparison group were hand-sutured. All the small bowels were subjected
      to leak pressure testing later on. The speed of closure and bursting pressure
      were compared. The 50 porcine small bowels closed by the high-frequency welding
      device showed a success rate of 100%. Compared with the hand-sutured group, the
      bursting pressures of the former were significantly lower (P<0.01) and the
      closing process was significantly shorter (P<0.01). The pathological changes of
      the closed ends mainly presented as acute thermal and pressure induced injury.
      Experimental results show that the high-frequency welding device has higher
      feasibility in closing the small bowel.

PMID- 25868255
TI  - [Evaluation of pathologic response of breast cancer to neoadjuvant chemotherapy
      with magnetic resonance diffusion weighted imaging].
AB  - This paper aims to investigate the value of diffusiion weighted imaging (DWI) and
      different apparent diffusion coefficient (ADC) methods to predict the curative
      effects of neoadjuvant chempotherapy (NAC) for breast cancer. From March 2010 to
      December 2012, seventy-one patients were pathologically confirmed invasive breast
      cancer by needle puncture biopsy received before surgery, and underwent magnetic
      resonance before and after NAC, the ADC were measured by mean ADC method and
      lower ADC method. The pathologic response after NAC was divided to major
      histological response (MHR) group and non-major histological response (NMHR)
      group according to Miller & Payne system. Results displayed that ADC values
      obtained before NAC, at the end of the second cycle of NAC, and after whole
      course of treatment, had good correlations between mean and lower ADC methods
      (the Pearson's correlation=0.699, 0.749 and 0.895, respectively). Significant
      difference in ADC obtained both with mean and lower ADC methods could be found
      between MHR and NMHR groups after the second cycle of NAC (P< 0.05). After the
      second cycle of NAC, significant difference in the change rate of ADC could be
      found between MHR and NMHR groups by using lower ADC method (P<0.05), but not be
      found by using mean ADC method (P >0.05). In conclusion, DWI could monitor the
      pathologic changes of breast cancer after NAC, and the lower ADC method might be
      used to evaluate the curative effect of NAC with the change rate of ADC.

PMID- 25868256
TI  - [Metrology research on biomedical engineering publications from China in recent
      years].
AB  - The present paper is to evaluate the scientific research level and development
      trends of biomedical engineering in China using metrology analysis on Chinese
      biomedical engineering scientific literatures. Pubmed is used to search the
      biomedical engineering publications in recent 5 years which are indexed by
      Science Citation Index, and the number and cited times of these publications and
      the impact factor of the journals are analyzed. The results show that comparing
      with the world, although the number of the publication in China has increased in
      recent 5 years, there is still much room for improvement. Among Chinese mainland,
      Hongkong and Taiwan, Chinese mainland maintains the obvious advantage in this
      subject, but Hongkong has the highest average cited number. Shanghai and Beijing
      have better research ability than other areas in Chinese mainland.

PMID- 25868257
TI  - [Research on fuzzy proportional-integral-derivative control of master-slave
      minimally invasive operation robot driver].
AB  - Robotic catheter minimally invasive operation requires that the driver control
      system has the advantages of quick response, strong anti-jamming and real-time
      tracking of target trajectory. Since the catheter parameters of itself and
      movement environment and other factors continuously change, when the driver is
      controlled using traditional proportional-integral-derivative (PID), the
      controller gain becomes fixed once the PID parameters are set. It can not change
      with the change of the parameters of the object and environmental disturbance so
      that its change affects the position tracking accuracy, and may bring a large
      overshoot endangering patients' vessel. Therefore, this paper adopts fuzzy PID
      control method to adjust PID gain parameters in the tracking process in order to
      improve the system anti-interference ability, dynamic performance and tracking
      accuracy. The simulation results showed that the fuzzy PID control method had a
      fast tracking performance and a strong robustness. Compared with those of
      traditional PID control, the feasibility and practicability of fuzzy PID control
      are verified in a robotic catheter minimally invasive operation.

PMID- 25868258
TI  - [Study of the influence of uniform transverse magnetic field on the dose
      distribution of high energy electron beam using Monte Carlo method].
AB  - In the present work, Monte Carlo simulations were employed to study the
      characteristics of the dose distribution of high energy electron beam in the
      presence of uniform transverse magnetic field. The simulations carried out the
      transport processes of the 30 MeV electron beam in the homogeneous water phantom
      with different magnetic field. It was found that the dose distribution of the 30
      MeV electron beam had changed significantly because of the magnetic field. The
      result showed that the range of the electron beam was decreased obviously and it
      formed a very high dose peak at the end of the range, and the ratio of maximum
      dose to the dose of the surface was greatly increased. The results of this study
      demonstrated that we could change the depth dose distribution of electron beam
      which is analogous to the heavy ion by modulating the energy of the electron and
      magnetic field. It means that using magnetic fields in conjunction with electron
      radiation therapy has great application prospect, but it also has brought new
      challenges for the research of dose algorithm.

PMID- 25868259
TI  - [Measurement method of arterial shear stress of rats model based on ultrasonic
      particle imaging velocimetry].
AB  - The development and progression of atherosclerosis and thrombosis are closely
      related to changes of hemodynamics parameters. Ultrasonic pulse wave Doppler
      technique is normally used for noninvasively blood flow imaging. However, this
      technique only provides one-dimensional velocity and depends on the angle between
      the ultrasound beam and the local velocity vector. In this study, ultrasonic
      particle image velocimetry method was used to assess whole field hemodynamic
      changes in normal blood vessels. By using the polynomial fitting method, we
      investigated the velocity gradient and assessed the shear in different blood flow
      velocity of 10 healthy rats. It was found that using four polynomial fitting
      could result in optimal measurement results. The results obtained by ultrasonic
      particle image velocimetry accorded with the results obtained using Doppler
      technique. The statistical average of cyclical vessel wall shear stress was
      positively related to the locational mean velocity. It is proven that ultrasonic
      particle image velocimetry method could be used to assess directly the real-time
      whole field hemodynamic changes in blood vessels and was non-invasively, and
      should be a good prosperous technique for monitoring complex blood flow in
      stenotic ar- teries.

PMID- 25868260
TI  - [Rapid simulation of electrode surface treatment based on Monte-Carlo model].
AB  - Micro- and integrated biosensor provides a powerful means for cell
      electrophysiology research. The technology of electroplating platinum black on
      the electrode can uprate signal-to-noise ratio and sensitivity of the sensor. For
      quantifying analysis of the processing method of electroplating process, this
      paper proposes a grid search algorithm based on the Monte-Carlo model. The paper
      also puts forward the operational optimization strategy, which can rapidly
      implement the process of large-scale nanoparticles with different particle size
      of dispersion (20-200 nm) attac- hing to the electrode and shortening a
      simulation time from average 20 hours to 0.5 hour when the test number is 10 and
      electrode radius is 100 microm. When the nanoparticle was in a single layer or
      multiple layers, the treatment uniformity and attachment rate was analyzed by
      using the grid search algorithm with different sizes and shapes of electrode.
      Simulation results showed that under ideal conditions, when the electrode radius
      is less than 100 /m, with the electrode size increasing, it has an obvious effect
      for the effective attachment and the homogeneity of nanoparticle, which is
      advantageous to the quantitative evaluation of electrode array's repeatability.
      Under the condition of the same electrode area, the best attachment is on the
      circular electrode compared to the attachments on the square and rectangular
      ones.

PMID- 25868261
TI  - [De-noising method research of ballistocardiogram signal].
AB  - Ballistocardiogram (BCG) signal is a physiological signal, reflecting heart
      mechanical status. It can be measured without any electrodes touching subject's
      body surface and can realize physiological monitoring ubiquitously. However, BCG
      signal is so weak that it would often be interferred by superimposed noises. For
      measuring BCG signal effectively, we proposed an approach using joint time
      frequency distribution and empirical mode decomposition (EMD) for BCG signal
      denoising. We set up an adaptive optimal kernel for BCG signal and extracted BCG
      signals components using it. Then we de-noised the BCG signal by combing
      empirical mode decomposition with it. Simulation results showed that the proposed
      method overcome the shortcomings of empirical mode decomposition for the signals
      with identical frequency content at different times, realized the filtering for
      BCG signal and also reconstructed the characteristics of BCG.

PMID- 25868262
TI  - [Study on the control of dynamic artificial limb ankle based on central pattern
      generator].
AB  - In order to obtain the normal gait for the prosthesis-carrier with the change of
      external environment and gait, we designed a model of dynamic ankle prosthesis
      and control system and introduced the strategy of central pattern generator (CPG)
      about the moving trail of dynamic ankle prosthesis. The dynamic parts, which are
      incorporated in the model of dynamic ankle prosthesis, provide power in order to
      have anthropic function and character. The tool of Matlab/simulink was used to
      simulate the strategy. The simulation results showed that the strategy of CPG
      learn- ing control in this study was effective and could track the reference
      trail rapidly and fit the moving trail of a person's normal limb. It can make the
      prosthetic timely regulation and action, enhance the prosthetic intelligence. It
      has im- portant practical value for intelligent prosthesis development based on
      this analysis of technology.

PMID- 25868263
TI  - [Construction and analysis of a monitoring system with remote real-time multiple
      physiological parameters based on cloud computing].
AB  - There have been problems in the existing multiple physiological parameter real
      time monitoring system, such as insufficient server capacity for physiological
      data storage and analysis so that data consistency can not be guaranteed, poor
      performance in real-time, and other issues caused by the growing scale of data.
      We therefore pro posed a new solution which was with multiple physiological
      parameters and could calculate clustered background data storage and processing
      based on cloud computing. Through our studies, a batch processing for
      longitudinal analysis of patients' historical data was introduced. The process
      included the resource virtualization of IaaS layer for cloud platform, the
      construction of real-time computing platform of PaaS layer, the reception and
      analysis of data stream of SaaS layer, and the bottleneck problem of multi
      parameter data transmission, etc. The results were to achieve in real-time
      physiological information transmission, storage and analysis of a large amount of
      data. The simulation test results showed that the remote multiple physiological
      parameter monitoring system based on cloud platform had obvious advantages in
      processing time and load balancing over the traditional server model. This
      architecture solved the problems including long turnaround time, poor performance
      of real-time analysis, lack of extensibility and other issues, which exist in the
      traditional remote medical services. Technical support was provided in order to
      facilitate a "wearable wireless sensor plus mobile wireless transmission plus
      cloud computing service" mode moving towards home health monitoring for multiple
      physiological parameter wireless monitoring.

PMID- 25868264
TI  - [Research state and prospect of modelling physical human and its applications].
AB  - Along with the development of computer technologies and digitization of human
      body's information, the digital human entered into a new stage of modelling
      physical features from the stage of reconstructing anatomical structures. By
      summarizing domestic and abroad relevant documents, we in this paper present the
      general scheme of digital human and the location of physical human as well as its
      conception and applied value. We especially analyze the modeling process of
      physical human, core technologies and its research and applications in four main
      fields: electromagnetic radiation, ultrasound propagation, bioimpedance
      measurements and biomechanical analysis. We also analyze and summarize existing
      problems of present physical human model and point out the future development
      trends of physical human.

PMID- 25868265
TI  - [Wireless human body communication technology].
AB  - The Wireless Body Area Network (WBAN) is a key part of the wearable monitoring
      technologies, which has many communication technologies to choose from, like
      Bluetooth, ZigBee, Ultra Wideband, and Wireless Human Body Communication (WHBC).
      As for the WHBC developed in recent years, it is worthy to be further studied.
      The WHBC has a strong momentum of growth and a natural advantage in the formation
      of WBAN. In this paper, we first briefly describe the technical background of
      WHBC, then introduce theoretical model of human-channel communication and digital
      transmission machine based on human channel. And finally we analyze various of
      the interference of the WHBC and show the AFH (Adaptive Frequency Hopping)
      technology which can effectively deal with the interference.

PMID- 25868266
TI  - [Advances in research on automatic exposure control of mammography system].
AB  - Mammography imaging is one of the most demanding imaging modalities from the
      point of view of the bal- ance between image quality (the visibility of small
      size and/or low contrast structures) and dose (screening of many asymptomatic
      people). Therefore, since the introduction of the first dedicated mammographic
      units, many efforts have been directed to seek the best possible image quality
      while minimizing patient dose. The performance of auto- matic exposure control
      (AEC) is the manifestation of this demand. The theory of AEC includes exposure
      detection and optimization and also involves some accomplished methodology. This
      review presents the development and present situa- tion of spectrum optimization,
      detector evolution, and the way how to accomplish and evaluate AEC methods.

PMID- 25868267
TI  - [Review on the research progress of mining of OMIM data].
AB  - Online Mendelian Inheritance in Man (OMIM) is a knowledge source and data base
      for human genetic diseases and related genes. Each OMIM entry includes clinical
      synopsis, linkage analysis for candidate genes, chromosomal localization and
      animal models, which has become an authoritative source of information for the
      study of the relationship between genes and diseases. As overlap of disease
      symptoms may reflect interactions at the molecular level, comparison of
      phenotypic similarity may indicate candidate genes and help to discover
      functional connections between genes and proteins. However, the OMIM has used
      free text to describe disease phenotypes, which does not suit computer analysis.
      Standardization of OMIM data therefore has important implications for large-scale
      comparison of disease phenotypes and prediction of phenotype-genotype
      correlations. Recently, standard medical language systems, term frequency-inverse
      document frequency and the law of cosines for document classification have been
      introduced for mining of OMIM data. Combined with Gene Ontology and various
      comparison methods, this has achieved substantial successes. In this article, we
      have reviewed various methods for standardization and similarity comparison of
      OMIM data. We also predicted the trend for research in this direction.

PMID- 25868268
TI  - [Recent development of research on the biotribology of carbon fiber reinforced
      poly ether ether ketone composites].
AB  - Carbon fiber reinforced poly ether ether ketone (CF/PEEK) composite possesses
      excellent biocompatible, biomechanical and bioribological properties. It is one
      of the most promising implant materials for artificial joint. Many factors
      influence the bioribological properties of CF/PEEK composites. In this paper, the
      authors reviewed on the biotribology research progress of CF/PEEK composites. The
      influences of various factors such as lubricant, reinforcement surface
      modification, functional particles, friction counterpart and friction motion
      modes on the bio-tribological properties of CF/PEEK composites are discussed.
      Based on the recent research, the authors suggest that the further research
      should be focused on the synergistic effect of multiple factors on the wear and
      lubrication mechanism of CF/PEEK.

PMID- 25868269
TI  - [Growth factors-mediated effects on the differentiation of human adipose-derived
      stem cells into chondrocytes].
AB  - In recent years, there has been a growing emphasis on use of human adipose
      derived stem cells (hADSCs) for cartilage tissue engineering owing to their
      ability to differentiate into chondrocytes, which is mainly induced by growth
      factors (GFs). In general, GFs for chondrogenic induction come from the
      transforming growth factor beta (TGF-beta) superfamily. To date, the most
      commonly used GFs for chondrogenes is TGF-beta1/3. However, the response of
      hADSCs to GFs may differ significantly from that of human bone marrow stem cells
      (hBMSCs). It has been reported that bone morphogenetic protein-6 (BMP-6)
      treatment induced TGF-beta receptor-I expression of hADSCs. It seems that these
      two cell populations varied strongly in their potency to undergo chondrogenesis
      in the same medium conditions. Here, we provide a concise review on various GFs
      used in chondrogenic differentiation of hADSCs in vitro.

PMID- 25868270
TI  - [NLRP3 inflammasome and diabetes].
AB  - Diabetes has become a global epidemic disease now. Its chronic progressive
      deterioration and the acuteand chronic complications affect the quality of the
      patients' lives seriously. The prevention and treatment of diabetes has become
      one of the research focuses in recent years. NLRP3 (NOD-like receptor family,
      pyrin domain containing 3) inflammasome can recognize the metabolic stress
      signals, and cause caspase-1 activation and interleukin-lp (IL-1p) production,
      and is closely related to diabetes development. The latest studies have shown
      that NLRP3 inflammasome will be a new potential target for the treatment of
      diabetes. This article reviews the activation and regulation of NL-RP3
      inflammasome, and the effect of NLRP3 inflammasome on glucose metabolism and its
      targeted therapy in diabetes.

PMID- 25868271
TI  - [Current research status and progress of stem cells therapy for degenerative
      intervertebral disc regeneration].
AB  - Low back pain caused by intervertebral disc degeneration is a common clinical
      chronic disease. The regenerative ability of intervertebral disc tissue is
      extremely poor. Meanwhile, current treating methods can not fundamentally solve
      such problems. With the increasing awareness of the mechanism of disc
      degeneration and the rapid development of the fields of cellular and molecular
      biology, gene and materials engineering, using stem cells and tissue engineering
      technology to slow down or reverse the progress of disc degeneration may become
      possible. The author reviewed the application of stem cells for treating
      degenerative discs from present researching status and concepts for the future in
      the combination of researches reported both at home and abroad.

PMID- 25868272
TI  - [[Virus-like particle-based immunoglobulin M capture enzyme-linked immunosorbent
      assay for the detection of IgM antibodies against Chikungunya virus].
AB  - To establish a MacELISA method for the detection of IgM antibodies against
      Chikungunya virus (CHIKV), we prepared virus like particle (VLP) antigens of
      CHIKV using the whole structural protein C-E3-E2-6K-E1 encoding gene with a
      baculovirus expression system in Sf9 insect cells. The VLPs were purified and
      used to immunize Kunming mice. Then, polyclonal antibodies were purified from the
      samples of ascites with a protein G HiTrap SP column and labeled with horseradish
      peroxidase. A MacELISA method for the detection of IgM antibodies against CHIKV
      was assembled with goat anti-human IgM antibody, VLP antigens and an enzyme
      labeled polyclonal antibody. The results were evaluated with a serum panel
      containing serum samples from laboratory-confirmed CHIK, HFRS patients, healthy
      donors, and commercially available CHIKV IgM as a quality control. It was shown
      that the MacELISA had a specificity of 99% (99/100), the coefficients of
      variation (CoV) within a plate were <10%, and the CoV of different ELISA plates
      in terms of the plate variation coefficient was <15%. A comparative analysis was
      performed to compare the current method against a commercial CHIKV IgM antibody
      detection kit for IIFA-IgM. The detection limit of MacELISA was significantly
      lower than that of the IIFA-IgM commercial kit (P< 0.0001). Here, we demonstrate
      that the VLP-based MacELISA is a promising tool for the early diagnosis and
      epidemiological investigation of CHIKV infection, with a high level of
      sensitivity and specificity for the detection of IgM antibodies against CHIKV.

PMID- 25868273
TI  - [Construction of cDNA infectious clones of EV71 highly-pathogenic and cell
      culture-adapted strains].
AB  - The highly-pathogenic EV71 strain is the primary cause of mortality in hand-foot
      and-mouth disease (HFMD) associated with neurological symptoms, for which no
      clinically effective drugs or vaccines exist. This study aimed to construct
      infectious cDNA clones of the EV71 highly-pathogenic strain and the cell-culture
      adapted strain using a reverse genetics approach. The genomic RNAs of EV71 parent
      strains were used as the templates for RT-PCR amplification, and then the PCR
      products that overlapped the full-length genome were connected into the pBR322
      vector to produce infectious clones of pEV71 (HP) and pEV71 (CCA), respectively.
      The results showed that the HP strain propagated much more quickly than the CCA
      strain. The rescued viruses derived from the infectious clones not only
      maintained their consistency with their parent strains in terms of genomic
      sequences, but also retained their respective biological phenotypes. This
      research will contribute to our understanding of EV71 pathogenesis and the
      development of novel vaccines against HFMD.

PMID- 25868274
TI  - [Seroprevalence of the newer enterovirus types A71, A90 and B87 in healthy
      individuals in Shandong Province, China].
AB  - This study aimed to investigate antibody levels of the newer human enteroviruses
      (EV) A71, A90, and B87 in the population of Shandong Province, and provide a
      scientific basis for the development of prevention and control measures. In this
      study, serum specimens were collected from 400 individuals living in Yantai city,
      Shandong Province in 2010. EV-A71, A90, and B87 antibodies were detected using
      neutralization tests, and the results were analyzed by statistical methods. It
      was found that the positive neutralizing antibody rates of EV-A71, A90 and B87 in
      the population were 46.0%, 8.8%, and 47.0%, respectively. Their geometric mean
      titers (GMT) were 1 : 5.20, 1 : 1.49, and 1 : 4.02, respectively. Positive
      antibody rates for EV-A71 and EV-B87 were lowest in the 1-yr and 7-mo age groups,
      respectively. Positive rates increased gradually with age, and become consistent
      in the population aged >5 years. Positive antibody rates of EV-A90 were
      consistent across all age groups. Maternal antibody levels of EV-A71 declined
      rapidly after birth, and the increase in seroprevalence among 3-7 years old
      children implied that most EV-A71 infections occurred in preschool and early
      elementary school children. High positive antibody rates of EV-B87 in healthy
      individuals, especially children, implied that there may be an immune barrier
      within the general population. The population monitoring of EV-A90 should be
      strengthened, as its positive antibody rate is low.

PMID- 25868275
TI  - [The suppressive effect of MiR-490 on coxsackievirus B3 replication].
AB  - To study the effect of miR-490 on Coxsackievirus B3 (CVB3) replication, HeLa
      cells were trans- fected with miR-490 in vitro, and infected with a Renilla
      luciferase (RLuc)-expressing CVB3 variant (RLuc-CVB3). The activities of RLuc in
      these cells were measured at 8h intervals from 0 to 40 h post-infection (p.i.),
      and the effects of miR-490 on RLuc-CVB3 replication were observed. In a further
      study, HeLa cells were transfected with either miR-490 or antisense miR-490 (AMO
      miR-490), and were then infected with an enhanced green fluorescence protein
      (EGFP)-expressing CVB3 variant (EGFP-CVB3). The replication of EGFP-CVB3 was then
      determined by detecting the expression of EGFP. We observed that miR-490 could
      significantly inhibit the expression of RLuc in infected cells at 32 h p. i.
      Furthermore, in HeLa cells infected with EGFP-CVB3 at 32 h p.i., EGFP expression
      was also significantly inhibited by the presence of mniR-490. The inhibitory
      effect of miR-490 on EGFP expression in EGFP-CVB3-infected cells could be
      reversed by tranfection with AMQ-miR-490. These results indicated that miR-490
      significantly inhibits the replication and expression of QVB3.

PMID- 25868276
TI  - [Molecular epidemiology of HFMD-associated pathogen coxsackievirus A6 in Fujian
      Province, 2011-2013].
AB  - In order to characterize the molecular epidemiology of HFMD-associated
      Coxsackievirus A6 (CVA6) in Fujian Province, a total of 1340 specimens from non
      EV71 non-CVA16 HFMD patients were collected during 2011-2013. Isolated virus
      strains were identified and subtyped. Full-length coding regions for the VP1 gene
      of the predominant serotype CVA6 isolates were amplified and sequenced. Among the
      375 non-EV71 non-CVA16 HFMD cases confirmed by virus isolation and molecular
      subtyping, 182 (48.5%) were found to be caused by CVA6, accounting for 7.9%,
      16.2% and 39.6% HFMD-associated enteroviruses in FujianProvince during 2011,
      2012, and 2013, respectively. Compared with general features observed in the HFMD
      epidemic, no difference in CVA6-specificity or severity rates was observed
      between geographical origins, gender, or age groups. Nucleotide sequence analyses
      of VP1 genes revealed high diversity levels of 16.2%-18.6% among CVA6 strains
      from Fujian Province, in contrast to the prototype CVA6 strain, and showed low
      levels of diversity in the amino acid sequences (4.3%-6.2%). Phylogenetic
      analysis also indicated that CVA6 isolates from Fujian Province were distinct
      from the prototype strain and other isolates from abroad; however, it was
      homologous to domestic strains, although the Fujian isolates clustered into
      multiple branches. These results suggested that significant changes in the
      pathogenic spectrum of HFMD in Fujian Province occurred during 2011-2013, as CVA6
      was one of the predominant serotypes of HFMD. CVA6 isolates from Fujian Province
      were co-circulating and co-evolving with other domestic strains as multiple
      closely related CVA6 transmission chains were observed in Fujian Province overall
      and within each prefecture.

PMID- 25868277
TI  - [Hand-foot-mouth disease pathogen separation and EV71 VP1 gene analysis in
      Sanmenxia City, Henan Province, China].
AB  - The aim of this study was to understand the enterovirus types and biological
      features of pediatric cases of HFMD in Sanmenxia City during 2011, and compare
      the latter to a cohort of healthy children. Stool samples of 55 cases of HFMD and
      60 healthy children were collected for the isolation and identification of
      enteroviruses using RNA extraction and real-time RT-PCR assays. EV71 and CA16
      were identified by nucleotide sequencing using virus-specific VP1 primers; for
      the other enteroviruses, 012/011 and 008/013 primers were used for amplification
      and sequencing. The results were analysed by sequence alignment with known
      sequences, and the characteristics of the EV71 VP1 gene were also analyzed. The
      detection rates for enteroviruses in cases of HFMD and healthy children were
      52.73% (29/55) and 18.33% (11/60), respectively. Among these, there were 22 cases
      of EV71, four cases of CA16 and three cases of other enteroviruses in the cases
      with HFMD. Eleven healthy children had intestinal viruses, of which nine were
      Coxsackie B virus strains (81.82%, 9/11). Gene sequencing of the 19 EV71 strains
      illustrated that they were all subgenotype C4a, but the evolutionary tree showed
      an obvious clustering between cases from Lingbao City and Lushi County. This
      study demonstrates that the EV71 subgenotype C4a and CA16 strains were the most
      common cause of HFMD in Sanmenxia City in 2011, and that Coxsackie B strains were
      prevalent in healthy children. This finding may indicate that there is a
      widespread source of recessive infection in the community.

PMID- 25868278
TI  - [Cell proteins that potentially interact with HBV polymerase were identified by
      co-immunoprecipitation-based LC-MS/MS identification and IPA].
AB  - Hepatitis B virus (HBV) is a major cause of chronic liver disease, and frequently
      results in hepatitis, cirrhosis, and ultimately hepatocellular carcinoma. HBV
      polymerase (Pol) is an essential viral protein that is important for HBV
      replication and might be involved in the development of hepatocellular carcinoma.
      Protein-protein interactions appears to be crucial for its role. The aim of this
      study was to screen and identify the proteins that interact with Pol using a co
      immunoprecipitation-based LC-MS/MS identification technique. The HBV Pol gene was
      amplified by polymerase chain reaction (PCR) and cloned into pCDNA3.1(+). The
      recombinant plasmid pCDNA3. 1(+)-Pol-flag was transfected into HeLa cells. Liquid
      chromatography and tandem mass spectrometry (LC-MS/MS) identified 45 proteins
      that co-immunoprecipitated with flag-tagged HBV Pol. Eleven of these have
      previously been reported as proteins that interact with HBV Pol. A proof-of
      concept-based Ingenuity Pathway Analysis (IPA, www.ingenuity.com) was used to
      characterize the functions and pathways of these 45 identified proteins and HBV
      Pol. Among these proteins, four proteins may play a role in three major molecular
      cellular networks, and are therefore worthy of further investigation.

PMID- 25868279
TI  - [A novel immunization strategy to induce strong humoral responses against HIV-1
      using combined DNA, recombinant vaccinia virus and protein vaccines].
AB  - To optimize the immunization strategy against HIV-1, a DNA vaccine was combined
      with a recombinant vaccinia virus (rTV) vaccine and a protein vaccine. Immune
      responses against HIV-1 were detected in 30 female guinea pigs divided into six
      groups. Three groups of guinea pigs were primed with HIV-1 DNA vaccine three
      times, boosted with rTV at week 14, and then boosted with gp140 protein at
      intervals of 4, 8 or 12 weeks. Simultaneously, the other three groups of animals
      were primed with rTV vaccine once, and then boosted with gp140 after 4, 8 or 12
      weeks. The HIV-1 specific binding antibody and neutralizing antibody, in addition
      to the relative affinity of these antibodies, were detected at different time
      points after the final administration of vaccine in each group. The DNA-rTV-gp140
      immune regimen induced higher titers and affinity levels of HIV-1 gp120/gp140
      antibodies and stronger V1V2-gp70 antibodies than the rTV-gp140 regimen. In the
      guinea pigs that underwent the DNA-rTV-gp140 regimen, the highest V1V2-gp70
      antibody was induced in the 12-week-interval group. However, the avidity of
      antibodies was improved in the 4-week-interval group. Using the rTV-gp140
      immunization strategy, guinea pigs boosted at 8 or 12 weeks after rTV priming
      elicited stronger humoral responses than those boosted at 4 weeks after priming.
      In conclusion, this study shows that the immunization strategy of HIV-1 DNA
      vaccine priming, followed by rTV and protein vaccine boosting, could strengthen
      the humoral response against HIV-1. Longer intervals were better to induce V1V2
      gp70-specific antibodies, while shorter intervals were more beneficial to enhance
      the avidity of antibodies.

PMID- 25868280
TI  - [Construction of a full-length cDNA clone of a live attenuated vaccine strain
      against Japanese encephalitis virus and preliminary study of expressing exogenous
      gene].
AB  - This study aimed to construct full-length cDNA clones of the Japanese
      encephalitis virus (JEV). SA14-14-2 strain and discuss the feasibility of
      constructing chimeric viruses for exogenous gene expression based on the JEV
      genetic skeleton. Long-fragment RT-PCR techniques were applied to amplify JEV cD
      NAs, and two amplified fragments with corresponding restriction endonuclease
      sites at both ends were cloned into the pACYC184 vector sequentially. Using
      standard molecular techniques, the enhanced green fluorescent protein (EGFP) gene
      was inserted into the 3' non-coding region of JEV as a reporter gene. After in
      vitro transcription and transfection procedures, wild-type JEV and chimeric JEV
      that expressed the EGFP as the reporter gene were successfully rescued. The
      recovered viruses were characterized by RT-PCR, plaque assays, and direct
      fluorescence microscopy. After six serial passage generations, the stability of
      the recovered viruses were studied in terms of virus growth characteristics and
      structural gene expression. The results showed that cDNA clones of rJEV and rJEV
      EGFP were successfully constructed and rescued in BHK-21 cells after in vitro
      transcription and transfection. Each generation of the recovered viruses was
      stable and the chimeric virus rJEV-EGFP could stably express EGFP. The findings
      of this study indicate that both rJEV and rJEV-EGFP could be constructed and
      rescued in BHK-21 cells, and the JEV SA14-14-2 strain could be obtained as a
      viral vector to express foreign genes.

PMID- 25868281
TI  - [Construction of rice stripe virus NS2 and NS3 Co-RNAi transgenic rice and
      disease-resistance analysis].
AB  - NS2 and NS3 are two post-transcriptional gene silencing suppressors that are
      encoded by Rice stripe virus. Gene silencing suppressors are always related to
      the pathogenicity of viruses. In this study, the cDNA of NS2 and NS3 were
      recombined by overlapping PCR assays, ligated to the RNAi vector, and inserted
      into the PXQ expression vector using Pst I; the expressed vector was transferred
      into calluses induced from seeds of the japonica rice cultivar, 'Nipponbare',
      using an Agrobacterium-mediated method. Thirty-one T0 transgenic plants were
      selected by G418 screening. PCR and southern blot analyses confirmed that the
      target gene was transformed into transgenic rice successfully, and different
      transgenic plants contained various copies of the gene. The disease resistance
      assay revealed that T0 transgenic rice had a delayed onset of RSV for
      approximately 10-20 d, and the accumulation of virus in the transgenic plants was
      reduced by 30%-50%. This was related to the delayed onset of disease.

PMID- 25868282
TI  - [Rescue of the recombinant infectious bronchitis virus with the ectodomain region
      of H120 spike glycoprotein].
AB  - To explore the expression potential of heterogeneous genes using the backbone of
      infectious bronchitis virus (IBV) Beaudette strain, the ectodomain region of the
      Spike gene (1,302 bp) of IBV H120 strain was amplified by RT-PCR and replaced
      into the corresponding location of the IBV Beaudette strain full-length cDNA.
      This recombinant was designated as BeauR-H120(S1). BeauR-H120(S1) was directly
      used as the DNA template for the transcription of viral genomic RNA in vitro.
      Then, the transcription product was transfected into Vero cells by
      electroporation. At 48 h post-transfection, the transfected Vero cells were
      harvested, and passaging continued. A syncytium was not observed until the
      recombinant virus had passed through four passages. The presence of rBeau
      H120(S1) was verified by the detection of the replaced ectodomain region of the
      H120 Spike gene using RT-PCR. Western blot analysis of rBeau-H120 (S1)-infected
      Vero cell lysates demonstrated that the nucleocapsid (N) protein was expressed,
      which implied that rBeau-H120(S1) could propagate in Vero cells. The TCIDs0 and
      EIDs0 data demonstrated that the titer levels of rBeau-H120(S1) reached 10(590+/
      0.22)TCID50/mL and 10(6.13+/-0.23)EID50/mL in Vero cells and 9-day-old SPF
      chicken embryos, respectively. Protection studies showed that the percentage of
      antibody-positive chickens, which were vaccinated with rBeau-H120(S1) at 7 days
      after hatching, rose to 90% at 21 days post-inoculation. Inoculation provided an
      85% rate of immune protection against a challenge of the virulent IBV M41 strain
      (103EID50/chicken). This recombinant virus constructed using reverse genetic
      techniques could be further developed as a novel genetic engineering vaccine
      against infectious bronchitis.

PMID- 25868283
TI  - [Model index observations in SIVmac251-infected rhesus macaques].
AB  - In this study, five rhesus macaques were inoculated intravenously with SIVmac251
      to establish a model of simian autoimmune deficiency syndrome (SAIDS). Peripheral
      blood samples were collected at different time points to monitor changes in the
      total T cell number and T lymphocyte subset. Plasma viral loads, cytokine
      expression levels and anti-SIV antibody levels were also assayed to acquire
      certain basic indexes to evaluate disease progression in the rhesus macaque SAIDS
      model. During the acute stage of infection, plasma viral loads reached a peak at
      week 1 post-inoculation and lasted for approximately 3 to 44 weeks. The CD3+ CD4+
      T lymphocyte count in peripheral blood also transitorily decreased. During the
      same period, the level of interferon-gamma show an increasing trend, whereas IL
      12 levels decreased; IL-2, IL-4, IL-10 and TNF-alpha were maintained at normal
      levels or could not be detected. During the asymptomatic and ARC phases, plasma
      viral loads persisted above 10(4) RNA copies/mL and either increased or declined
      during the later stages of disease; CD3+ CD4+ counts showed a steadily declining
      trend and the ratio of CD4 to CD8 decreased during late-stage disease. Moreover,
      antibodies against viral proteins were detected in the plasma and showed a
      significant increasing trend, while there were no apparently changes in the
      levels of IFN-gamma, IL-12, IL-2, IL-4, IL-10 and TNF-alpha. In conclusion, the
      characteristics of the SIV animal models in our study are similar to those of
      patients with AIDS. Therefore, the rhesus macaque SIVmac251 infection models can
      be applied for further studies into AIDS.

PMID- 25868284
TI  - [Research progress in the structure and function of dengue virus non-structural 1
      protein].
AB  - Dengue virus (DENV) is a re-emerging disease transmitted by the Aedes mosquitoes
      and has become a major public health problem in southern China. Currently, no
      antiviral drug or effective vaccine exist to control this disease. The chimeric
      DENV structural protein vaccine cannot elicit balanced levels of protective
      immunity to each of the four viral serotypes; therefore, non-structural protein
      components may be required to construct an effective DENV vaccine. The Dengue
      virus non-structural 1 (DENV NS1) protein plays a critical role in viral
      pathogenesis and protective immunity. Therefore, immunity to Dengue 1-4 NS1
      subtypes may be crucial for the prevention of severe disease. This review
      attempts to provide an overview about the structure and function of DENV NS1.

PMID- 25868285
TI  - [Research progress in novel PA protein members of influenza A viruses].
AB  - Influenza poses a great threat to life and health in populations worldwide.
      Studies regarding the protein components of influenza viruses will facilitate the
      research and development of vaccines and diag nostic reagents. The influenza
      virus contains both structural and non-structural proteins. From the outset, it
      has been accepted that an influenza A virus possesses eight gene segments that
      encode eight corresponding viral proteins, respectively. Research has
      demonstrated that the M gene encodes the M2 ion channe! protein and the NS gene
      encodes the non-structural protein, NS2. In recent years, several novel viral
      proteins have been identified from influenza A viruses. This article will briefly
      describe the state of current research into PA-related proteins of influenza A
      viruses.

PMID- 25868286
TI  - [A review of research on Schmallenberg virus].
AB  - Schmallenberg virus (SBV), a novel orthobunyavirus, was first isolated in 2011.
      SBV preferentially infects the central nervous system of cattle and sheep and
      causes fever, diarrhea, a drop in milk yields, congenital malformations and
      stillbirths. Until June 2014, more than 200 scientific publications regarding SBV
      have been published. Although more than 20 articles on SVB were published in
      China, most of these articles provided only a brief introduction of the disease
      without fully discussing the associated disease characteristics. As a new
      disease, it has been made a focus of the National Research Center for Exotic
      Animal Diseases at the China Animal Health and Epidemiology Center. In this
      review, in order to provide a reference for research into SBV in China, we have
      reviewed the state of current research progress on the etiology, diagnosis and
      epidemiology of SBV, and vaccine development.

PMID- 25868287
TI  - [Recent progress of the mechanisms for RNA viruses to block the recognition of
      dsRNA with RIG-I-like receptors].
AB  - RIG-I-like receptors (RLRs) belong to pattern recognition receptors, which
      perform significant roles in antiviral responses. RLRs can initiate a cascade of
      signaling transduction that induces the production of type I interferon and
      activates the interferon signaling pathway, ultimately resulting in antiviral
      responses. In the course of evolution, viruses have been constantly counteracting
      host immune systems to facilitate their own survival and replication, and have
      developed a set of antagonistic strategies. These mainly comprise elusion,
      disguise and attack strategies to eliminate the activation of RLRs. In virus
      infected cells, RLRs recognize viral RNA and then induce antiviral responses. A
      better understanding of viral antagonistic strategies against RLRs will provide
      insights into the development of new antiviral medicines. This mini-review
      concludes that there are three main antagonistic strategies by which RNA viruses
      can counteract the activation of the RLRs pathway. It aims to provide references
      and insights for similar studies on viral antagonism in an array of RNA viruses.

PMID- 25868288
TI  - [New Strategy for anti-HBV therapy: blocking P-8 interaction].
AB  - Clinically being applied treatment against chronic hepatitis has three
      limitations: low response rates, severe adverse effects and a high rate of drug
      resistance. Hence, novel targets for antiviral therapy need to be developed so as
      to provide an armory of different strategies. During the replication of hepatitis
      B virus, the interaction of viral polymerase (P protein, also called P) and
      epsilonRNA is indispensable for the initiation of reverse transcription via
      protein priming and the pregenome RNA (pgRNA) packaging. Three strategies are
      currently developed for blocking P-epsilon interaction: heat shock protein
      inhibitors, epsilonaptamers and chemical compounds for blocking formation of P
      epsilon complex. Previously, our group has for the first time worldwide in vitro
      screened several aptamers, which are able to interfere with the P-epsilon
      interaction. A strong inhibition against HBV was observed in vitro and in vivo
      experiments, respectively. In conclusion, the so far developed chemicals
      suppressing the P-epsilon interaction may bypass or overcome the viral resistance
      problems during clinic treatment and represent a highly attractive option for
      therapeutic intervention.

PMID- 25868289
TI  - Law, order, and lows.

PMID- 25868290
TI  - Counting sleep.

PMID- 25868291
TI  - Ready, set, go.

PMID- 25868292
TI  - Top tech on the horizon.

PMID- 25868293
TI  - Diabetes through the ages.

PMID- 25868294
TI  - Blood glucose meters.

PMID- 25868295
TI  - Ketone test strips.

PMID- 25868296
TI  - The basics of continuous glucose monitors.

PMID- 25868297
TI  - The basics of insulin pumps.

PMID- 25868298
TI  - The basics of infusion sets.

PMID- 25868299
TI  - Insulin pens.

PMID- 25868300
TI  - Aids for insulin users.

PMID- 25868301
TI  - Glucose products.

PMID- 25868302
TI  - Your food.

PMID- 25868303
TI  - A failure to communicate.

PMID- 25868304
TI  - Left ventricular systolic function in selected type 1 diabetic patients with or
      without diabetic retinopathy and microalbuminuria.
AB  - Vascular endothelial dysfunction is a basic etiologic factor for the development
      of late clinical complications in patients with diabetes mellitus type 1, such as
      diabetic retinopathy, diabetic nephropathy (which is characterized at the very
      beginning by microalbuminuria), and left ventricular cardiac dysfunction. The
      aims of this study were to determine the prevalence of asymptomatic left
      ventricular systolic dysfunction in patients with diabetes mellitus type 1 and
      with or without diabetic retinopathy and microalbuminuria, and to correlate the
      duration of diabetes with the dynamics of diabetic retinopathy, microalbuminuria
      and asymptomatic left ventricular dysfunction development in these patients. One
      hundred and twenty selected patients with diabetes mellitus type 1 were examined
      by ophthalmologist and cardiologist. All patients underwent ergometric testing
      and two-dimensional (2-D) echocardiography with pulsed Doppler. Patients were
      divided into three groups according to their fundus findings and
      microalbuminuria: (1) patients without diabetic retinopathy and without
      microalbuminuria (n = 40); (2) patients with diabetic retinopathy without
      microalbuminuria (n = 40); and (3) patients with diabetic retinopathy and
      microalbuminuria (n = 40). All three groups of patients with diabetes mellitus
      type 1 (with low cardiovascular risk, regulated blood sugar, and without diabetic
      neuropathy) had echocardiographic values in the normal range. We found no
      statistically significant correlation between the duration of diabetes mellitus
      type 1 and echocardiographic values.

PMID- 25868305
TI  - Effect of delays on survival in patients with lung carcinoma in Montenegro.
AB  - Lung cancer is a global medical problem with a rising incidence and 5-year
      survival of 5%-10%. The aim of this study was to investigate whether waiting
      times and delays in diagnosis and treatment of patients with lung carcinoma have
      any bearing on prognosis and survi- val. The study was performed in the Brezovik
      Special Hospital for Lung Diseases and Tuberculosis. The study included all cases
      with the diagnosis of lung carcinoma in the Republic of Montenegro in 2009, a
      total of 206 patients, with follow up until the end of 2010. Median age was 66,
      median Karnofsky score 80, and male to female ratio 5:1. Diagnostic procedure was
      bronchoscopy in 89% of patients. Histologic type was small cell lung cancer in
      25.7% and non small cell lung cancer in 74.3% of cases. Surgery was the main
      treatment for 24.4% of patients. Median delay from first symptoms to diagnosis of
      lung cancer was 10.35 weeks, mean 8 weeks (median patient's delay was 6.20 weeks,
      doctor's delay at primary health care 2.07 weeks and in pulmonology services 2.37
      weeks). Median survival time for all patients was 39.27 weeks, mean 34. There was
      no statistically significant diffe- rence between patient's delay/doctor's
      delay/total delay and stage of lung carcinoma at the time of diagnosis, treatment
      choice and survival. Our results indicate that longer delay is not associated
      with poorer prognosis of lung carcinoma. The possible ways of reducing mortality
      of lung cancer include prevention by decreasing smoking prevalence and improved
      therapeutic options.

PMID- 25868306
TI  - Oral health changes during early phase of orthodontic treatment.
AB  - The aim of the study was to assess the influence of fixed orthodontic appliance
      on Streptococcus (S.) mutans and S. sobrinus counts in orthodontic patients with
      regard to their previous caries experience (Decayed, Missing and Filled Teeth
      (DMFT) index) during the first 12 weeks of orthodontic treatment. Twenty-two
      patients that satisfied inclusion criteria (healthy systemic and periodontal
      condition, avoidance of antibiotic therapy and antiseptic mouthwashes in the past
      three months) were included. All clinical measurements took place prior to and 12
      weeks after fixed orthodontic appliance placement, in the following order: 1)
      stimulated saliva flow (SS); 2) Simplified Oral Hygiene Index (OHI-S); and 3)
      DMFT. The method of polymerase chain reaction (PCR) was used to detect the
      presence of S. mutans and S. sobrinus at T1 and T2. T-test showed significant
      increase in DMFT index and SS between T1 and T2. Results also indicated
      significant improvement in OHI-S index. By use of the PCR method, S. mutans was
      detected in two patients at T1. At T2, two more patients had S. mutans, but the
      increase was not statistically significant. Using the same method, S. sobrinus
      was detected only in two patients at T2. In conclusion, fixed orthodontic
      appliances did not induce statistically significant changes in caries microflora
      even in the presence of enhanced oral hygiene habits.

PMID- 25868307
TI  - Pain syndromes in multiple sclerosis patients - patient experience at Lipik
      Special Hospital for Medical Rehabilitation.
AB  - In the study, we evaluated 61 multiple sclerosis patients hospitalized at our
      hospital in the period from October 1, 2013 to February 15, 2014. The aim of the
      study was to investigate pain syndromes associated with the underlying disease.
      Pain in the month preceding assessment was reported by 90% of patients. Most
      patients suffered from low back pain (52%) and musculoskeletal pain (39%),
      followed by neck pain (31%), painful tonic spasm (26%), neuropathic extremity
      pain (23%) and pain due to spasticity (21%). Other types of pain were present in
      less than 20% of patients. A total of 67% of patients were taking analgesics; the
      most frequently used were nonsteroidal antiinflammatory drugs, while drugs
      against neuropathic pain were taken by a smaller number of patients. The high
      incidence of pain syndromes pointed to the importance of regular physical therapy
      procedures.

PMID- 25868308
TI  - Psychiatric comorbidities among patients with epilepsy in Montenegro.
AB  - The aim of this study was to evaluate the prevalence of psychiatric
      comorbidities, depression and anxiety, among patients with epilepsy in the
      outpatient Clinic for Epilepsy, Clinical Centre of Montenegro. Patients aged 18
      and above with a diagnosis of epilepsy for at least one year were consecutively
      enrolled during a six-month period. Patients anonymously filled out a
      questionnaire which included data on the gender, age, education, marital status
      and degree of seizure control. The Hamilton Depression Rating Scale (HAM-D) and
      Hamilton Anxiety Rating Scale (HAM-A) were used to evaluate the presence or
      absence of anxiety and depression. Total number of study patients was 70,
      including 52 patients with partial seizures and 18 patients with generalized
      tonic-clonic seizures. The mean patient age was 37 +/- 7.92 years. The prevalence
      of depression in our sample was 32.8%, whereas the prevalence of anxiety was
      21.4%. Patients with partial seizures were more depressed, while those with
      idiopathic generalized seizures were more anxious (p < 0.01). Depression was
      associated with a lower educational level, unemployment and poor seizure control
      (p < 0.05). The number of antiepileptic drugs showed a trend towards negative
      association with depression (p = 0.005). Anxiety was associated with the level of
      education and uncontrolled seizures (p < 0.01). Neither depression nor anxiety
      was associated with age, gender, marital status, age at onset and duration of
      epilepsy. Psychiatric disorders among patients with epilepsy are quite common but
      yet under-recognized. Therefore, appropriate recognition and efficient treatment
      of these disorders in patients with epilepsy might improve their quality of life
      and could consequently lead to better treatment success.

PMID- 25868309
TI  - The use of piezoelectric effect to improve instrument quality and patient safety
      in laparoscopic surgery.
AB  - The piezoelectric properties of some natural crystals and polymers can also be
      used in surgery. For this purpose, a prototype of an endoscopic instrument was
      constructed with piezoelectric material attached to its working end with the aim
      of recognizing pulsating blood vessels during laparoscopic surgery. To test the
      properties of the new instrument in laboratory conditions, simulated blood
      circulation was used with the possibility of changing pressure and frequency. The
      instrument was tested in the pressure range of 40-180 mm Hg at constant frequency
      of 72/min and frequency range of 36-130 beats per minute at constant pressure of
      120 mm Hg. Test results showed that the instrument with certainty recognized a
      pulsating "blood vessel" in the expected pressure ranges and at different blood
      pump frequencies. Given the piezoelectric material's very small dimensions and
      flexible form, it can be installed at the working end of most standard
      laparoscopic instruments and thus significantly increase certainty in the
      recognition of arteries during surgery, which would reduce the possibility of
      their injury or accidental ligation.

PMID- 25868310
TI  - Person-oriented perspectives in neurology.
AB  - Person-oriented medicine is characterized by a holistic approach in patient ma-
      nagement that embraces physical, psychological, social and spiritual aspects of
      health and dise- ase. It responds to the needs of patients and health care
      workers to form an effective therapeutic relationship based on trust, empathy,
      compassion and responsiveness to the individual needs of a patient. Person
      oriented perspectives in neurology include active collaborative partnership
      between a physician and a patient, and intuitive perception, which has a
      neurobiological correlate in the hu- man mirror neuron system, thus expressing a
      considerable impact on the quality of the physician's diagnostic and therapeutic
      activities. On the other hand, personalized approach in medicine implies
      integration of clinical information and personal genotyping. Personalized
      neurology provides gene- based preclinical prediction of disease with improved
      risk assessment, early detection of disease and targeted intervention. The
      combination of personalized approach and clinical information accelera- tes the
      translation of genetic discoveries into clinical practice, which ultimately
      results in improved health care system. Person-oriented perspectives contribute
      significantly to the growing pluralism of medical science and provide a greater
      humanization of medicine, individualized treatment and autonomy during
      therapeutic processes.

PMID- 25868311
TI  - Sports and health: equivalence or contrariety.
AB  - Playing sports is a widely known method of health promotion. Balanced exercise
      and diet are keys to healthy life. However, sports activities can cause different
      injuries, from joint to head injuries. Although head injuries cause a variety of
      acute and chronic disorders, they are often undertreated. There are 1.6 million
      injured people examined at emergency departments throughout Europe every year. In
      sports like boxing, football, soccer, hockey, handball, basketball and bicycling,
      head injuries occur at a frequency of 4% to 22%. Particularly significant are
      chronic difficulties that occur after recurrent head injuries, i.e. cognitive
      deficits and changes in electroencephalogram. Qualifications of professional
      personnel are insufficient for professional evaluation and treatment of head
      injuries. The best way for sports to become an important link in health and
      disease prevention is to go back to sports basics while using acquired scientific
      knowledge.

PMID- 25868312
TI  - Treatment of complex tibial plateau fractures using Ilizarov technique.
AB  - Complex tibial plateau fractures are most commonly caused by high-energy trauma
      and they are often associated with severe soft tissue injuries that can
      frequently result in severe complications. Ilizarov external circular fixation is
      an ideal method of treatment for high- energy fractures of the tibial plateau
      when extensive soft tissue dissection and internal fixation are contraindicated.
      Our research included 50 consecutive patients and clinical features of the
      patients were evaluated during the follow up period using the following
      instruments: Gustillo-Anderson, Sc- hatzker and Arbeitsgemeinschaft fur
      Osteosynthesefragen/Orthopaedic Trauma Association (AO/ OTA) classification
      methods. Bony results were evaluated using the Association of the Study and
      Application of the Method ofIlizarov (ASAMI) protocol. The mean functional
      recovery scores were obtained by the modified functional evaluation system of
      Karlstrom-Olerud. All fractures healed successfully. Circular fixators could be
      removed without anesthesia for type IV fractures at 16 weeks (range 12-21) and
      for type V-VI at 18 weeks (range 15-26) after the operation. According to ASA- MI
      bone results, there were 39 (78%) excellent, 7 (14%) good, 3 (6%) fair results
      and 1 (2%) poor result. Analysis of data obtained by the Karlstrom-Olerud
      functional evaluation system in this study yielded a mean value of 24.7 after six
      months, which implies recovery. Functional recovery at 12 months after surgery
      revealed satisfactory recovery with a mean value of 27.7, whereas the mean sco-
      re of 29.8 recorded at the last evaluation suggested good functional status. The
      treatment of patients with open and closed multiple intra-articular fractures of
      proximal tibia applying Ilizarov apparatus showed good functional outcome, which
      had positive impact on our patients' quality of life.

PMID- 25868313
TI  - The use of neuroimaging in the management of chronic headache in children in
      clinical practice versus clinical practice guidelines.
AB  - In daily practice, neuroimaging studies are frequently performed for the
      management of childhood headache. The aim of this study was to determine whether
      there is significant discrepancy between clinical practice and clinical practice
      guidelines on the indications for neuroimaging studies. Medical records of
      children with chronic headache, aged 2 to 18 years and treated at Rijeka
      University Hospital Center, Kantrida Department of Pediatrics, were
      retrospectively reviewed. Indications for brain magnetic resonance imaging and
      computed tomography (MRI/CT) scanning were reviewed and compared with clinical
      practice guidelines. Brain imaging was performed in 164 (76.3%) of 215 children,
      MRI in 93 (56.7%) and CT in 71 (43.3%) children. Indications for brain MRI/CT
      were as follows: anxiety and/or insistence by the child's family (71.3%),
      presence of associated features suggesting neurologic dysfunction (13.4%), age
      under 5 years (12.8%) and abnormal neurologic examination (2.4%). The majority of
      children (71.4%) had normal neuroimaging findings. In the rest of imaging studies
      (28.1%), MRI/CT revealed different intracerebral/extracerebral findings not
      influencing changes in headache management. Only one (0.60%) patient required
      change in headache management after MRI/CT. Study results proved that, despite
      available evidence-based clinical guidelines, brain imaging in children with
      chronic headaches is overused, mostly in order to decrease anxiety of the
      family/patient.

PMID- 25868314
TI  - The evolution of partial nephrectomy for kidney tumors--are we abandoning the
      basic principles of Robson's radical nephrectomy?
AB  - Fifty years ago, Robson introduced radical nephrectomy (RN) setting the gold
      standard for treating kidney tumors. Experience has shown that partial
      nephrectomy (PN) can be equally effective with the advantages of preserving
      kidney function and avoiding unnecessary nephrectomies for benign tumors. The
      purpose of this report is to demonstrate the evolution of clinical presentation
      and choice of treatment for patients with kidney tumors at our department,
      emphasizing changes in the PN utilization trends. Clinical data were abstracted
      for the years 2002, 2007 and 2012. We assessed annual trends for changes in the
      choice of operative treatment related to tumor size, pathologic stage and
      diagnosis. During the study, there was an increase in the share of T1 tumors,
      from 46.6% in 2002 to 69.8% in 2012. The rate of PN increased more than ten-fold,
      from 2.7% in 2002 to 31.7% in 2012. The annual rates of PN for T1 tumors
      increased even more, from 6.6% in 2002 to 46.7% in 2012. Opposite to RN group,
      there was an increase in the mean tumor size in PN group (from 1.8 cm in 2002 to
      3.9 cm in 2012). The rate of RN for benign tumors was reduced impressively from
      85.7% in 2002 to 23.1% in 2012. Our data argue strongly that PN should be
      expanded and not restricted. Robson's principles have been partially deserted
      over the last decade; however, proving that PN is superior to RN still remains to
      be elucidated.

PMID- 25868315
TI  - Clinical view of the temporomandibular joint disorder.
AB  - Temporomandibular pain has a musculoskeletal origin because it occurs as a
      consequence of masticatory muscle function disorder and temporomandibular joint
      disorder. Most common diagnoses of disorders are disc displacement and
      osteoarthritis, but their comorbidity can also occur. Pain is the most common
      symptom, where chronic temporomandibular pain may con- tribute to the occurrence
      of psychological disorders in the patient population. Splint is the most
      widespread dental method of treatment but other, noninvasive methods of
      musculoskeletal pain treatment are also recommended. Electronic axiography is
      used for visualization of mandibular movements, in particular pathologic sounds
      in the joints. Mental health, although not so obvious in dental practice, can
      influence the need of a multidisciplinary approach to the patient with disorder
      of the temporomandibular joint.

PMID- 25868316
TI  - Is chronic groin pain a Bermuda triangle of sports medicine?
AB  - Chronic groin pain is one the most complex conditions encountered in the field of
      sports medicine. Conservative treatment is long lasting and the result of
      treatment is often uncer- tain and symptom recurrences are common, which can be
      very frustrating for both the patient and the physician. The complex etiology and
      uncertainties during treatment of chronic groin pain is the reason why some
      authors call it the Bermuda Triangle of sports medicine. In our prospective, 7
      year study, 114 athletes with chronic groin pain resistant to conservative
      therapy were treated surgically. In 109 athletes with sports hernia, we performed
      nerve neurolysis along with resection of the genital branch of the genitofemoral
      nerve and we also reinforced the posterior wall of inguinal canal using a
      modified Shouldice technique. In 26 athletes that had concomitant adductor
      tendinosis and in 5 athletes with isolated tendinosis we performed tenotomy.
      Eighty-one of 83 patients with isolated sports hernia returned to sports within a
      mean of 4.4 (range, 3-16) weeks. Thirty-one athletes with adductor tenotomy
      returned to sports activity within a mean of 11.8 (range, 10-15) weeks. If
      carefully diagnosed using detailed history taking, physical examination and
      correct imaging techniques, chronic groin pain can be treated very successfully
      and quickly, so it need not be a Bermuda Triangle of sports medicine.

PMID- 25868317
TI  - Cerebellar dermoid cyst with contrast enhancement mural nodule: case report.
AB  - Typical dermoid cysts are well-circumscribed fat-density masses with no
      associated contrast enhancement; rarely, they may appear hyperattenuating on CT
      scan. CT hyperattenuating dermoid cyst (CHADC) is very uncommon, with only nine
      case reports in the literature update, which occurs exclusively in the posterior
      fossa. CHADC with mural nodule is extremely rare and, to the best of our
      knowledge, only two cases have been documented previously in the literature. A 49
      year-old farmer had a 2-month history of occipital headaches, which were not
      suggestive of raised intracranial pressure. During the last month, he experienced
      loss of balance, frequent falls, anorexia and loss of weight. Magnetic resonance
      imaging (MRI) showed a huge mass from the tentorium to the foramen occipitale
      magnum with obliteration of the fourth ventricle; the lesion was well
      circumscribed. We completely removed the tumor and postoperative MRI showed no
      residual tumor. Epidermoid tumors with enhancing mural nodule on MRI and with
      hyperattenuating lesion on CT are extremely rare. Dermoid cysts are never
      associated with edema and extremely rarely cause obstructive hydrocephalus. MRI
      investigations are mandatory to diagnose these cases. The best curative treatment
      is total removal of the lesion.

PMID- 25868318
TI  - Tongue carcinoma with endobronchial metastasis: a rare case.
AB  - Endobronchial metastases of extrapulmonary malignant tumors are quite rare. We
      present a patient with endobronchial metastasis previously operated for tongue
      carcinoma. A 71-year-old female patient presented with the complaint of cough.
      She had a history of tongue carcinoma operation 2 years before. Chest x-ray
      revealed an air-fluid level in the lower zone of the right hemithorax. There was
      a big cavitary lesion in the right lower lobe and bilateral multiple nodular
      lesions, some of which had cavity formation on computed tomography. Bronchoscopy
      re- vealed a polypoid lesion with necrotic appearance and pathologic examination
      showed squamous cell carcinoma. The lesion was accepted as a metastasis of tongue
      carcinoma after evaluation of the materials taken from the tongue on previous
      operation. There was no finding suggestive of local recurrence; however, the
      patient died from hemoptysis and respiratory insufficiency. In conclusion,
      endobronchial metastasis should be considered in patients with extrapulmonary
      malignancies and bronchoscopic examination should be performed in such cases,
      even in the presence of atypical radiological findings.

PMID- 25868319
TI  - Transcatheter patent foramen ovale closure and radiofrequency ablation of right
      atrial tachycardia.
AB  - Patent foramen ovale (PFO) can be found in approximately 25% of adult population.
      Transcatheter closure of PFO is a potential option in selected patients with PFO.
      We report a case of a female patient that underwent mapping and catheter ablation
      of atrial tachycardia and PFO closure in the same procedure.

PMID- 25868320
TI  - Complete neurological recovery after surgery for mesencephalic cavernoma: case
      report.
AB  - Cavernous malformations are classified as a group of vascular malformations of
      the central nervous system. Conservative treatment of brainstem cavernomas is
      accompanied with poor outcome. Surgery ofbrainstem cavernomas still poses a
      challenge due to the high risk of neurological damage and respectable morbidity.
      We report a case of complete neurological recovery in a 24-year-old female
      patient with mesencephalic cavernoma treated surgically. This case highlights
      that careful microsurgical treatment with the goal of complete cavernoma excision
      remains the treatment of choice in cases with de novo or recurrent hemorrhage.
      Intraoperative neurophysiologic monitoring should be used as the gold standard
      during brainstem cavernoma operations in order to avoid nuclear and long tract
      damages.

PMID- 25868321
TI  - Historical review.

PMID- 25868322
TI  - [Reactive oxygen species are triggers and mediators of an increase in cardiac
      tolerance to impact of ischemia-reperfusion].
AB  - Reactive oxygen species (ROS) are triggers of ischemic preconditioning (IP). On
      the role of intracellular messengers of such cardioprotective effect of
      preconditioning claim: O2*, H2O2, OH*. However, we cannot exclude the possibility
      that other reactive oxygen metabolites also involved in the IP. Presented data
      suggest that IP enhances the production of ROS. The source of ROS may be
      mitochondrial respiratory chain and NADPH oxidase. Exogenous reactive oxygen
      species (O2*, H2O2) mimic the cardioprotective effect of preconditioning.
      Preconditioning prevents free radical damage of the heart during ischemia
      reperfusion. The protective effect of IP is the consequence of reducing the
      production of ROS or the result of increased formation of endogenous
      antioxidants. Antioxidant enzymes are not involved in the protective effect of
      IP. Cardioprotective effect of many compounds (bradykinin, opioids,
      acetylcholine, phenylephrine, tumor necrosis factor-alpha, volatile anesthetics,
      protonophores, diazoxide, angiotensin II) depends on the increased production of
      ROS.

PMID- 25868323
TI  - [Involvement of distal fragment of chromosome 13 in the regulation of sensitivity
      to ethanol in mice].
AB  - The role of the fragment 57-65 cM of mouse chromosome 13 was studied in the
      regulation of ethanol action on locomotor activity, anxiety and sensitivity to
      hypnotic and hypothermic effects of ethanol. We used male mice of recombinant
      lines AKR/J and AKR.CBA-D13Mit76C, differing only in this fragment. After acute
      administration of ethanol only AKR mice showed the increase in the length of
      traveled distance in the open-field test (p < 0.05), only the AKR.CBA-D13Mit76C
      mice demonstrated the increase the time spent in the center of open-field arena
      (p < 0.05). Intact animals of both lines did not differ in sleep duration and
      intensity of hypothermia induced by injections of high doses of ethanol. At the
      same time, long-term alcohol treatment led to the weakening of the hypnotic
      effect of ethanol in the males of both lines compared to intact animals (p < 0.01
      for the AKR, p < 0.001 for AKR.CBA-D13Mit76C). Chronic alcoholization led to
      increased ethanol-induced hypothermia in AKR males compared to intact animals (p
      < 0.01) and did not affect the intensity of ethanol hypothermic effect in AKR.CBA
      D13Mit76C mice. The results suggest the involvement of the distal fragment 57-65
      cM of chromosome 13 in the mechanisms of ethanol action in mice.

PMID- 25868324
TI  - [Pecularities for action of combined administration of NAN-190 and ketanserine
      with low dose of 17beta-estradiol on depression-like behavior in prenatally
      stressed ovariectomized rats].
AB  - The aim of the present work was to perform a comparative analysis of 5-HT(1A)-
      and 5-HT(2A/2C)-receptors blockade effects on depression-like behavior of the
      adult ovariectomized (OVX) female offspring at estrogen deficiency delivered from
      their prenatally stressed mothers. The adult prenatally stressed OVX female
      offspring were chronically (during 14 days) treated by 5-HT(1A)-receptors
      antagonist--NAN-190 (0.1 mg/kg, s. c.) or 5-HT(2A/2C)-receptors antagonist-
      ketanserine (0.1 mg/kg, i. p.) alone, or in a combination with its preparartions
      a low dose of 17beta-estradiol (5.0 MUg/rat, s. c.). All drugs were administered
      in 2 weeks after overiectomy during 14 days before and for all period of
      behavioral testing procedure. The prenatally stressed QVX female offspring were
      tested in the forced swimming test (FST) and the open field test (OFT). Treatment
      with NAN-190 alone induced marked depressant-like effect, while NAN-190
      administered in a combination with a low dose of 17beta-estradiol resulted in an
      antidepressant-like effect in the FST in the prenatally stressed OVX females as
      compared to the control prenatally stressed female offspring. Administration
      ofNAN-190 plus 17beta-estradiol led to decreased frequency of rearing,
      exploratory and grooming behavior in prenatally stressed OVX female offspring in
      the OFT. Treatment with ketanserine resulted in an antidepressant-like effect in
      prenatally stressed OVX females in the FST as compared to the control group.
      However, co-administration of ketanserine with a low dose of 17beta-E2 to the
      prenatally stressed OVX female offspring failed to modify depressant-like
      behavior in the FST.

PMID- 25868325
TI  - [Pulmonary hemodynamics following experimental myocardial ischemia after the
      blockade of adrenergic receptors].
AB  - In acute experiments in anesthetized rabbits the changes of the pulmonary
      hemodynamics following 60 s myocardial ischemia in the region of the descendent
      left coronary artery were studied in control animals and after the blockade of
      alpha-adrenoreceptors by phentolamine or beta-adrenoreceptors by propranolol.
      Following myocardial ischemia in control animals the pulmonary artery pressure
      and flow decreased, the pulmonary vascular resistance did not change, the left
      atrial pressure elevated; the cardiac output decreased more than pulmonary artery
      flow. Following myocardial ischemia after the blockade of beta-adrenoreceptors
      the pulmonary artery pressure decreased more than in control animals, the
      pulmonary artery flow was decreased in the same level as in the last case. The
      pulmonary vascular resistance was diminished, the left atrial pressure increased;
      the pulmonary artery flow and cardiac output decreased in the same level.
      Following myocardial ischemia after the blockade of beta-adrenoreceptors the
      pulmonary artery pressure and pulmonary vascular resistance decreased more than
      after the blockade of alpha-adrenoreceptors, the left atrial pressure did not
      change. In both cases the pulmonary artery flow decreased in the same level and
      its changes were correlated with venous return shifts. The differences of the
      pulmonary artery changes following myocardial ischemia after the blockade of
      alpha- and beta-adrenoreceptors are caused not only the different pulmonary
      vascular resistance changes, but also the left atrial pressure.

PMID- 25868326
TI  - [Comparative analysis of the potentiative effect of noradrenaline on the
      neurogenic vasoconstriction diminished by various factors].
AB  - The effect of 0.03-1.0 MUM noradrenaline on the neurogenic response to electrical
      field stimulation of the juvenile rat tail artery segment in control conditions,
      after cooling from 36 to 25 degrees C, and after solution pH decrease from 7.4 to
      6.6 was studied. Noradrenaline was shown to potentiate neurogenic
      vasoconstriction diminished by low temperature or low pH. Decrease in neurogenic
      vasoconstriction being equal, low dose noradrenaline was most effective at low
      temperature and high dose noradrenaline was most effective at low pH. 1.0 MUM
      noradrenaline was equally effective in both cases. Increase in the neurogenic
      tone of the rat tail artery evoked by noradrenaline at low temperature and
      acidosis may contribute to decrease in heat emission at low ambient temperature
      in vivo.

PMID- 25868327
TI  - [Translocation of MuRF isoforms to nuclei in postural muscle during gravitational
      unloading].
AB  - Ubiquitin-proteasomal proteolytic pathway is one of the key signaling pathways
      determining protein degradation in muscle fibers. Among the E3 ubiquitin ligases,
      rate limiting enzymes of the ubiquitin-proteasomal pathway, the most interesting
      ones are the MuRF isoforms: MuRF-1 and MuRF-2. There are some pieces of evidence
      that these enzymes are also involved in the regulation of gene expression in
      skeletal muscle under some specific conditions (i. e. muscle disuse). We supposed
      that it was disuse that brought about to altered localization of MuRFs in
      postural muscle fibers and their translocation to nuclei. In the study using the
      conventional simulation model of the gravitational unloading (rat hindlimb
      suspension according to Ilyin and Novikov modified by Morey-Holton) we found that
      from the 3rd day till 14th day of unloading the content of MuRF-1 and MuRF-2 in
      the nuclear fraction 4-5 fold increased in unloaded soleus as compared to the
      control values. These data obtained by means of electrophoresis and western blot
      of the nuclear fraction of rat soleus were confirmed in the immunohistochemical
      study of co-localization of MuRF-1 and MuRF-2 antibodies and DAPI nuclear stain
      on transverse frozen sections of soleus muscle. Thus in the present study we
      observed the phenomenon of MuRF isoforms accumulation in nuclei of soleus muscle
      fibers during simulated gravitational unloading.

PMID- 25868328
TI  - [GAP-43 and its proteolytic fragment in spinal cord cells of rats with
      experimental autoimmune encephalomyelitis].
AB  - The regenerative capacity of the Central Nervous System (CNS) is a key factor
      implicated in the pathogenesis of neurodegenerative diseases. In the present
      study, the regenerative capacity of the CNS is considered using one of the
      markers of regeneration, Growth Associated Protein-43 (GAP-43) and its
      proteolytic fragment GAP-43-3 in the Experimental Autoimmune Encephalomyelitis
      (EAE) animal model of multiple sclerosis. The EAE on Wistar rats was
      characterized as an adequate model of multiple sclerosis, with typical clinical
      (pares and paralysis) and morphological (infiltration of spinal cord and
      deformation of motoneurons) disorders. Normally about 60% of GAP-43 is cleaved by
      m-calpain and stays in the form of GAP-43-3. During severe form of EAE up to 85%
      of GAP-43 can be found cleaved. We speculated that the cleavage of GAP-43 can
      play a crucial role for regenerative capacity of CNS during EAE development. Thus
      the distribution of GAP-43 and GAP-43-3 in the spinal cord was analyzed. The
      manifestation of clinical signs of EAE has been found to be in correlation with
      the levels of GAP-43 proteolysis both in the homogenate of the spinal cord and on
      the spinal cord slices. The immunoreactive staining enabled the observation of
      the accumulation of GAP-43-3 predominantly in microglial cells.

PMID- 25868329
TI  - [Specific characteristics of mismatch negativity in infants].
AB  - The mismatch negativity component of auditory event-related potentials was
      studied in fulI-term infants of the first month of life and adults. Acoustic
      stimuli with large deviance in passive oddball task were used. Research data
      revealed distinctive features in morphology and specificity in parameters of
      positive mismatch component in children at early ages. Contrary to results from
      adult group infant component was manifested in two positive peaks, greater
      amplitude and longer latency. A significant positive correlation was observed
      between infant's conceptual age and amplitude, and significant negative
      correlation was found between gestation age and latency for this positive
      component. Results allowed proposing specificity in parameters of infant's
      positive mismatch component indicated proceeding maturational changes in auditory
      cortex at early ages.

PMID- 25868330
TI  - [Heart rate variability and blood pressure during mental stress].
AB  - The goal of this study was to evaluate the changes in blood pressure (BP) and
      heart rate variability (HRV) parameters due to a mental load. The findings
      indicate that mental arithmetic stress causes prompt increases in BP, heart rate
      and induced decreases in HRV. A shift toward an increase in sympathetic tone and
      changes in Poincare plot measures were observed during mental stress. The present
      study demonstrates that mental stress leads to an increase in predictability,
      regularity of the RR intervals and decreased value of complexity measures, that
      reflects a change towards more stable and periodic behavior of the heart rate
      under stress. Linear Discriminant Analysis shows that CCM and SampEn achieving
      the best results in detecting stress condition, and the latter indicates that
      chaos being inherent to the physiological control of heart rate.

PMID- 25868331
TI  - [Spectral parameters of heart rate variability in man under the acute normobaric
      hypoxia conditions].
AB  - Spectral parameters (SP) of heart rate variability (HRV) and a duration of
      cardiointervals (RR) in 14 healthy male volunteers at the age of 23-36 years
      under the influence of acute normobaric hypoxia by respiratory gas oxygen
      nitrogen mixture (9% O2, 25 min) were studied. The 300 cardiocycles at each of
      six experimental time points by ECG at II standart lead were registered. The
      parameters before hypoxia were (M +/- m): RR (s) 0.90 +/- 0.03; SP powers (ms2)
      TP 13 553 +/- 2789; VLF 3885 +/- 902; LF 4724 +/- 1062; HF 4945 +/- 1165. All
      parameters were about 21-25% less as compared to background in the 5th min of
      hypoxia. The decreasing was about 17% (RR) and 34-38% (SP) in the 10th min of
      hypoxia. At the 20th min of hypoxia all parameters but RR were increased to the
      background level. At last after hypoxia in the 5th min parameters RR were at the
      background level, SP were to 1.5-2 times higher. In the 15th min all parameters
      returned to initial levels.

PMID- 25868332
TI  - [The regulation of negative and positive emotions during picture viewing: an ERP
      study].
AB  - The study examines the effects of cognitive reappraisal on the event-related
      potentials (ERPs) to affective stimuli. Participants (n = 53) were asked either
      to attend affective images, or to down-regulate negative affect, or to up
      regulate positive affect. Reappraisal of negative images was associated with
      attenuation of the P300 and late positive potential (LPP) over parietal regions,
      whereas reappraisal of positive images had no significant effect on ERP
      components. The weak P300 reduction correlated with high personality scores of
      negative affectivity. We assume that only down-regulation of negative emotions is
      associated with the changes in primary appraisals, and so far reflected in ERP
      modulation.

PMID- 25868333
TI  - [Features of oxygen utilization by the body of patients with arterial
      hypertension in the days of magnetic storms depending on the psychosomatic status
      and treatment options].
AB  - During magnetic storms the observed increase in gamma-background environment and
      the reduction of the rate of oxygen utilization by the tissues, but the increase
      in the number of angina attacks per day to magnetic storms the choleric, in the
      days of magnetic storms in sanguine, for 3-4 days at a phlegmatic, and 4-5 days
      in the melancholic especially in groups high anxiety phlegmatic and melancholic.
      Last-risk group severe arterial hypertension and ischemic heart disease.
      Antihypertensive therapy based on the blockade of the features of the
      psychosomatic status, significantly reduced the number of attacks and brought the
      values of the utilization of oxygen and coefficient of oxygen utilization bu the
      tissues of all the days to those in healthy individual relevant anxiety and
      temperament.

PMID- 25868334
TI  - [Influence of exam stress on the development of endothelial dysfunction and the
      formation of platelet-leukocyte coagregates].
AB  - The aim of this work was to study the qualitative and quantitative composition of
      circulating endotheliocytes, P-selectin-associated leukocyte and platelet of
      coogregation blood levels of endothelin, interleukin-6 students on the background
      of exam stress. The research was made on the group conditionally healthy
      volunteers aged MT 18.3 +/- 1 years that before participating in the study had a
      medical examination (n = 15). Blood sampling was made three times: 1--three
      months before the session (in a normal school day, two hours after training
      sessions), 2--for 25 +/- 10 min before the exam, 3 - 15 +/- 10 min after the
      exam. Approved the development of endothelial dysfunction in the background of
      exam stress, manifested by increased levels of circulating endothelial cells and
      endothelin. The total number of leukocyte and platelet of coogregation during the
      semester, before and after the exam has not changed, while there was an increase
      outlets, due to the expression of P-selectin on red blood cells before the exam
      and precipitous decline after the exam.

PMID- 25868335
TI  - [Disallowed conformations of polypeptide chain exemplified by the beta-bend of
      the beta-hairpin in the alpha-spectrin CH3-domain].
AB  - The work presents the results of an exhaustive conformational analysis of beta
      turns involving amino acid residues with disallowed backbone conformation of the
      polypeptide chain. It is known that the first residue of the beta-turn (Asn47) of
      the distal beta-hairpin in the alpha-spectrin SH3-domain is characterized by
      sterically disallowed main chain conformation (values of the dihedral angles (phi
      and psi are in the right bottom quadrant of the Ramachandran plot). All alpha
      spectrin structures with the anomalous elements deposited in the PDB were
      analysed. We hypothesized that the formation of disallowed conformation may occur
      through the fixation (due to the SH3 domain structure) of the adjacent to the
      beta-turn amino acid residues with the beta-structure. These residues are
      disposed in such a manner that beta-turn conformation of the residues contributes
      just to the disallowed local conformation of this residue whereas any other beta
      turn conformations (with allowed local conformation) are impossible. To test this
      hypothesis an exhaustive conformational analysis of the beta-bend has been
      performed by altering internal coordinates (two pairs of phi and psi angles and
      two Omega angles). The conformations were selected as a result of grid search
      procedure with. 1 degrees step that corresponded to stereochemically allowed
      local deformations of the polypeptide chain segment forming the beta-turn. In all
      conformations obtained the local conformation of Asn47 rests in the disallowed
      region. The conformations found include conformations coinciding with
      experimentally determined structures from the PDB as well as an additional
      variant that differs from X-ray structure in values of a pair of phi and psi
      angles of the second residue belonging to the beta-bend. Values of these angles
      fall in the region of the Ramachandran plot near the line phi = 0 (and negative
      values of psi) i.e. in strongly disallowed region without experimental points.
      Therefore the additional variants of the beta-turn local deformation are
      impossible to observe in experiment. Thus, the idea that disallowed conformation
      is intruded to the beta-bend by fixation of adjacent residues receives
      confirmation in this work. The topological limitations in a context of the
      structure in such kind of beta-hairpins exclude the allowed local conformations.

PMID- 25868336
TI  - ["Co-phased blocks"--conservative regions of double-stranded DNA of
      transcriptional regulatory modules--are close in space due to phasing at
      nucleosome DNA super helix].
AB  - Conservative regions varying in length from 30 to 70 nucleotides (nt) are
      revealed as a result of interspecies comparison of homologous nucleotide
      sequences of the loci, genes controlling early development in Drosophila species.
      These regions are observed at the intermediate level between transcription factor
      binding sites (usually about 7-10 nt) and the nucleosome repeat unit (165-210
      nt). Segments found are located mainly in the area of known functional elements
      of the locus (cis-regulatory modules: enhancers, a proximal promoter, a coding
      segment). Conservative domains occupy less than a half of the full enhancer
      length and contain practically all annotated transcription factor binding sites.
      A quasi periodical pattern of conservative region disposition is in accord with
      the experimental nucleosome localization pattern. The distance between
      neighboring domains is about 84 nt, i.e. a pitch of nucleosome DNA super helix. A
      repeatable accuracy of the distance permits of treating the delineated
      conservative regions as co-phased blocks and stating that these domains are close
      in the space being located at neighboring coils of the nucleosome DNA super
      helix.

PMID- 25868337
TI  - [Comparative efficiency of algorithms based on support vector machines for binary
      classification].
AB  - Methods of construction of support vector machines require no further a priori
      infoimation and provide big data processing, what is especially important for
      various problems in computational biology. The question of the quality of
      learning algorithms is considered. The main algorithms of support vector machines
      for binary classification are reviewed and they were comparatively explored for
      their efficiencies. The critical analysis of the results of this study revealed
      the most effective support-vector-classifiers. The description of the recommended
      algorithms, sufficient for their practical implementation, is presented.

PMID- 25868338
TI  - [On the possibility of analysis of biopolymer fragments by tunneling microscopy].
AB  - An image of fragmented sequence of biopolymer molecules by example of bacterial
      DNA in vivo (in atmosphere air) was received by scanning tunneling microscopy. An
      air adsorbate (mainly water vapors) that covers the molecule's surface gives rise
      to local tunnel conductivity and by virtue of adsorption selectivity indirectly
      reflects local conductance of fragments that consist of different rows of various
      atoms, supporting their tunnel conductivity. Having processed experimental data
      fragment images are obtained with scaled-up topography characteristics for their
      further identification.

PMID- 25868339
TI  - [Effect of dilution on aggregation of nanoparticles of polycarboxylic derivative
      of fullerene C60].
AB  - In this work, we investigated the effect of dilution on aggregation of
      nanoparticles of the polycarboxylic derivative of fullerene C60. It is shown that
      the diminution of the concentration of PCDF-1 in aqueous medium leads to a
      decreased amount of aggregates of fullerene and an increased amount of single
      molecules. This can potentially interfere with the biological activity of a
      compound on one molecule basis. Addition of organic and inorganic salts to the
      aqueous medium with fullerene derivative leads to intense disaggregation of PCDF
      1. The data obtained suggest an explanation of non-stoichiometric nature of
      neutralization of reactive oxygen species by derivatives of fullerenes, as well
      as provide new insight into the physical meaning of the work on the impact of
      nanoparticles at ultra-low concentrations on biological objects.

PMID- 25868340
TI  - [Conformational states of NADH molecules in hydrated shell under weak
      electromagnetic irradiation].
AB  - The work deals with spectra of capillary waves of water distillate and water
      solution of NADH and dynamics of NADH under electromagnetic irradiation in the
      range of millimeters at different space frequencies of surface wave k.

PMID- 25868341
TI  - [Supramolecular reorganizations in cellulose during hydration].
AB  - The analysis of modern ideas about the structural organization of the cellulose
      microfibrils is carried out. The mechanism of the formation of additional
      capillary-porous system of cellulose under moistening is offered. It is
      established that when the moisture content of cellulose reaches 8-10%, the
      filling of its micropores occurs with a simultaneous increase in their cross
      sizes, a specific surface and reduction in the degree of crystallinity of
      specimens. Within the proposed model of microfibril construction the parameters
      of supramolecular structure and capillary-porous system of cotton cellulose are
      determined.

PMID- 25868342
TI  - [Spectral characteristics and monosaccharide composition of interferon-inducing
      antiviral polysaccharide from Heliantnus tuberosus L].
AB  - This article presents the results of spectral analysis, monosaccharide
      composition and interferon-inducing properties of the polysaccharide from
      Heliantnus tuberosus L. Based on the spectral characteristics and the
      monosaccharide composition it was concluded that polysaccharide belongs to glucan
      class, presumably--beta-glucan. It has been shown that the polysaccharide complex
      of the Heliantnus tuberosus L. cell wall exhibits interferon-inducing properties
      both in experiments in vitro, and in vivo. It has been supposed that in
      polysaccharide stimulated models interferon is produced for all three species-
      alpha, beta, gamma. Antiviral and therapeutic effects of polysaccharide were
      shown.

PMID- 25868343
TI  - [Water-soluble polysaccharide from Heliantnus tuberosus L.: radioprotective,
      colony-stimulation and immunomodulation activities].
AB  - Experimental data on the presence of immunomodulatory activity, colony
      stimulation and radioprotective properties of the polysaccharide from Heliantnus
      tuberosus L. with the molecular weight of 1-2 MDa, were obtained. The effect of
      different concentrations of the polysaccharide on production of TNF-alpha, IL
      1beta and IL-6 was studied. The nature of radioprotective properties of the
      polysaccharide is discussed: stimulation of growth of colonies of hematopoietic
      stem cells, direct interaction with the products of ionizing radiation, and
      stimulation of cytokine cascades. The possibility of further usage and studying
      of the polysaccharide is discussed.

PMID- 25868344
TI  - [Atomic force microscopy monitoring of temperature dependence of cytochrome BM3
      oligomeric state].
AB  - The change in temperature is one of the factors affecting the activity of
      enzymes. In this work thermal denaturation and aggregation of cytochrome P450 BM3
      were studied by atomic force microscopy. To determine specific temperature
      transitions the fluorescence analysis was used. In the low melting temperature
      range, 10-33 degrees C, a decrease in the fluorescence intensity of aromatic
      residues was observed with an increase in the fluorescence intensity of flavin
      groups. Protein melting in this range indicated three narrow S-shaped cooperative
      transitions at temperatures 16, 22 and 29 degrees C. Atomic force microscopy
      analysis in this temperature range showed that the shape of BM3 molecules
      remained globular in the form of compact objects (heights h < 7 nm, lateral
      dimensions d < 50 nm), but protein oligomeric state changed. The first two
      transitions were accompanied by a decrease in the degree of oligomerization and
      the third one was accompanied by its increase.

PMID- 25868345
TI  - [Diffusion studies of redox-sensitive nitroxyl spin probes through bilayer lipid
      membranes using 300 MHz electron spin resonance spectrometer].
AB  - Electron spin resonance (ESR) studies were carried out for 14N-labeled deuterated
      3-methoxy-carbonyl-2,2,5,5-tetramethyl-pyrrolidine-1-oxyl (MC-PROXYL) and 3
      carboxy-2,2,5,5-tetramethyl-1-pyrrolidin-1-oxyl (carboxy-PROXYL) in pure water
      and various concentrations of liposomal solutions by using 300 MHz ESR
      spectrometer. The ESR parameters such as the line width, hyperfine coupling
      constant, rotational correlation time, g-factor, partition parameter and
      permeability were reported for the samples. The line width broadening was
      observed for MC-PROXYL and carboxy-PROXYL in liposomal solution. The hyperfine
      coupling constant was observed for both nitroxyl spin probes. The permeable and
      impermeable nature of nitroxyl spin probes was demonstrated. The rotational
      correlation time increases with increasing concentration of liposome. The
      partition parameter increases with increasing concentration of liposome for MC
      PROXYL, which indicates that the nitroxyl spin probes diffuse into lipid
      membrane. The permeability value decreases with increasing concentration of
      liposome, which reveals an increase in membrane permeability. The peaks
      corresponding to the lipid phase were observed for MC-PROXYL in liposomal
      solution, but not resolved for carboxy-PROXYL. These results confirm the
      permeable and impermeable nature of nitroxyl spin probes.

PMID- 25868346
TI  - [Lipid pore states in bilayer lipid membranes at phase transition in LiCl
      solution with addition of polyethylene glycols].
AB  - Statistics on open and closed states of the lipid pores was experimentally
      investigated in planar lipid bilayer membranes from
      dipalmitoylphosphatidylcholine at the phase transition temperature in LiCl
      solution (1 M). Polyethylene glycol of different molecular mass was added to the
      solution. Transmembrane current pulses were measured at voltage-clamp conditions
      (50 mV). The histograms of the pore lifetime and the pulse interval have no
      exponential shape but the pronounced maximum. It means that the pulse sequence of
      the transmembrane current measured in the phase conditions is dependent. The
      emergence of the new pulses depends on the emergence time of the previous pulses.
      The time of the pulse end depends on the time of the pulse start. The proposed
      Erlang model approximates the experimental histograms quite accurately. According
      to the model the lipid pore can have several open and closed states.

PMID- 25868347
TI  - [Low doses of ionizing radiation-induced apoptotic nature of erythrocyte
      hemolysis].
AB  - It is established that exposure of the red blood cells of the rats to low doses
      of ionizing radiation (0.04; 0.08; 0.16; 0.25 and 0.33 mGr) leads to non-linear
      changes in the processes of lipid peroxidation in the membrane of erythrocytes,
      their electrophoretic mobility, osmotic resistance. In a dose range from 0.08 to
      0.16 mGr with ionizing radiation apoptosis that determines a temporary slowing of
      the process of hemolysis and stabilization of erythrocytes that is confirmed by
      morphological changes in erythrocytes is most likely triggered.

PMID- 25868348
TI  - [Spectral measurements of functional heterogeneity of cells and their
      organelles].
AB  - The microspectral analysis technique was used to identify molecular components of
      a number of plant and animal cells. This technique allows of performing optical
      measurements during freezing down to the temperature of liquid nitrogen. Revealed
      biochemical heterogeneity suggests functional specialization of individual cells
      within a population. Analysis of the fluorescence quenching revealed temperature
      intervals in which processes of recrystallization of intracellular water
      associated with specific pigment-protein complexes take place. A proposed
      experimental approach may find its application in correlation microscopy and also
      in cryobiology in order to search after optimal modes for the freezing and
      thawing of cryopreserved cells.

PMID- 25868349
TI  - [Phenolic antioxidant TS-13 regulating ARE-dependent genes induces tumor cell
      death by mitochondria-dependent pathway].
AB  - Effects of water-soluble phenolic antioxidant sodium 3-(3'-tret-butyl-4'
      hydroxyphenyl)-propyl thiosulfonate (TS-13), potassium 3,5-dimethyl-4
      hydroxybenzyl thioetanoate (BEP-11-K) and potassium 3-(3',5'-ditretbutyl-4'
      hydroxyphenyl)-propionate (potassium phenosan) on tumor cells proliferative
      activity and the role of redox-dependent and calcium-dependent signaling
      mechanisms in realization of tumor cell response to the antioxidant action were
      studied. Potassium phenosan and BEP-11-K were found to stimulate proliferation
      and ARE-inducing phenolic antioxidant TS-13 was found to inhibit tumor cell
      growth in culture. The tumor cell growth rate depended on the rate of
      intracellular reactive oxygen species production and was decreased by apocynin (a
      NADPH-oxidase inhibitor) and antimycin A (an ubiquinol-cytochrome c
      oxidoreductase inhibitor). TS-13 action on tumor cells was accompanied by a
      transient increase in intracellular reactive oxygen species production and the
      intracellular calcium concentration, whereas cell incubation with potassium
      phenosan and BEP-11-K did not influence the reactive oxygen species level and
      intracellular calcium ions. Cyclosporine A blocked the inhibitory effect of TS
      13. Thus, it can be reasonably speculated that phenolic antioxidant TS-13 starts
      mitochondria-dependent apoptosis in tumor cells by the opening of permeability
      transition pores.

PMID- 25868350
TI  - [Tyndall's hypochromism in suspensions].
AB  - Since the passage of light through each individual particle in a suspension
      includes the competition of processes of absorption and scattering, it leads to
      hypochromism--a decrease in the extinction coefficient. Such "scattering"
      hypochromism increases with the particle size and its refractive index. Since the
      Tyndall's light scattering in suspensions, where the size of each particle is
      substantially larger with respect to wavelengths of light, is not strongly
      dependent on the wavelength, the absorption spectrum (and excitation spectrum)
      attenuated almost uniformly at different wavelengths. A simple method to find
      true extinction coefficients from the absorption (or excitation) spectra of
      diluted suspensions (not having multiple light scattering) is suggested. The
      experimental data on spectra of hemoglobin in erythrocytes, actinomycin in DNA
      and flavins in mitochondria are given.

PMID- 25868351
TI  - [Effect of water isotopic composition on Rhodococcus erythropolis biomass
      production].
AB  - The effect of water isotopic composition on concentration of oil-oxidizing
      actinobacteria Rhodococcus erythropolis VKM Ac-2017D cellular biomass is observed
      during cultivation in liquid nutrient media. The value for the effect was
      determined by experimental conditions, including consecutive use of hydrophilic
      and hydrophobic nutritious substrates--saccharose and hexadecane. It is shown,
      that when Rhodococcus erythropolis VKM Ac-2017D cells, cultivated in media with
      sucrose and 71 and 98 ppm deuterium content in water were inoculated into the
      similar in mineral and isotopic composition media with hexadecane, a considerable
      increase in cellular biomass production is observed if compared to a control
      sample in which water with 150 ppm deuterium concentration was used.

PMID- 25868352
TI  - [The dependence of fluorescence in phytoplankton on external influences].
AB  - Phytoplankton is the main source of oxygen and the primary link in the food chain
      for water objects; it plays an important role in their ecological state. The
      influence of environment parameters on intensity of fluorescence is not
      considered when measuring concentration by a fluorescence method. In this work
      the dependence between fluorescence of chlorophyll a contained in phytoplankton
      cells and the water temperature and illuminating intensity is theoretically and
      experimentally proved. The formula for a coefficient of proportionality which
      allows calculating concentration of chlorophyll a is offered taking into account
      environment parameters. The use of the coefficient calculated in this study
      allows reducing an error when chlorophyll a concentration is measured by the
      fluorescence method. Distributions of the phytoplankton chlorophyll concentration
      in depth calculated with the use of a conventional technique and the coefficient
      obtained are shown. Phytoplankton fluorescence was measured by a fibro-optic
      spectrometer in the water area of the Peter Velikiy Bay in September-October,
      2013.

PMID- 25868353
TI  - [Anti-nitrosative system as a factor of malignant tumor resistance to cytotoxic
      effect of nitrogen monooxide].
AB  - The inhibitory action of binuclear dinitrosyl iron complexes with glutathione on
      the growth of implanted solid tumor in BDF1 mice bearing Lewis lung carcinoma
      cells was found. The effect was induced by intraperitoneal injection of the
      binuclear dinitrosyl iron complexes to mice at a dose of 200 MUM/kg daily on days
      1-5 and 7-11. At the binuclear dinitrosyl iron complexes: free glutathione ratios
      of 1:1; and 1:10 in solutions, the inhibitory effect of the DNICs reached the
      level of 70% and 85%, respectively. When B-DNICs were not further infused,
      intensive tumor growth, a more rapid rate of tumor growth than control, was
      observed. The selective accumulation of DNICs as well as iron nitrosyl complexes
      of heme-containing proteins in tumors were detected by EPR method. The latter
      were found also in the tumors in control animals. Tumor growth delay in course of
      B-DNIC administration to the mice is supposed to be due to the elaboration of
      anti-nitrosative defense in tumor tissue in response to the action of NO released
      from B-DNIC.

PMID- 25868354
TI  - [Effects of weak magnetic fields on different phases of planarian regeneration].
AB  - We analyzed the effects of weak combined magnetic fields, tuned to the cyclotron
      resonance condition for calcium ions, obtained in different phases of planarian
      regeneration. We showed that the result of regeneration in 72 hours after
      decapitation depends on the length of exposure, and the time between decapitation
      and initiation of a half-hour exposure. The experimental dependence can be
      explained by a multiplicity of enzymatic targets activated in different phases of
      the regeneration process.

PMID- 25868355
TI  - [Assessment of cilium force on the foot sole of the freshwater snail Lymnaea
      stagnalis].
AB  - In this study, we evaluated the force of the cilium on the foot sole of a medium
      sized pond snail Lymnaea stagnalis, crawling up in the anaerobic water. It was
      found that there are 1.3 x 10(9) cilia on the foot sole, their force is 1.47 x
      10(-6) W, the force of one cilium is 1.1 x 10(-15) W and the force of single
      ciliary beat is 1.1 x 10(-16) W.

PMID- 25868356
TI  - [Luminescent and physiological indices of triticale under the treatment of seeds
      with growth regulators].
AB  - It is shown that the before-sowing treatment of triticale seeds with growth
      regulators epin and zircon resulted in the increase in the F742/F686 ratio of the
      stationary fluorescence intensities of the plant leaves at the wavelength bands,
      742 and 686 nm, corresponding to the maxima in the leaf fluorescence spectrum.
      Triticale under the treatment of seeds with growth regulators showed higher
      chlorophyll content, higher productivity and higher indices of the crop yield.

PMID- 25868357
TI  - [Regular thermal waves in female mammary glands].
AB  - During experimental studies of thermal regime of female mammary glands tissues
      the existence of periodic thermal waves was discovered. At the same time, the
      space-amplitude relief of such waves can mask the space-amplitude relief of the
      thermal profile, projected to the skin surface of mammary glands by tumor, hidden
      in the thickness of the gland. The phenomenon observed would be taken into
      account upon diagnosing pathological states of mammary glands.

PMID- 25868358
TI  - [Tidal variations of radon activity as a possible factor for synchronization of
      biological processes].
AB  - Possible scenarios for synchronization of some biological processes with
      variations in Lunar-Solar gravitational tide acceleration, based on the trigger
      influence of the tidal force on geological environment and the relevant
      modulation of the emanation and activity fields of radon and other radioactive
      elements, are considered. Mechanisms and models of sensitivity of biological
      systems to the tidal variations of natural background radiation, including
      mitochondrial permeability transition, generation of reactive oxygen species and
      reactive nitrogen species, bystander factors, secondary biogenic radiation,
      modulation of cell signaling and rhythmic gene expression, are discussed.

PMID- 25868359
TI  - [Anomalies of the time dependences of electrical conductance of water on its
      cooling].
AB  - The dependence G(t) of electrical conductance G of Millipore water on time t was
      studied on its cooling down below 25 degrees C. The water was placed into a
      stainless, non-hermetic, cylindrical container with a working volume of 650 ml.
      The study was conducted by the ac capacitance method with immersion of the
      measuring electrodes in the studied water. It was found, that the change in the
      distribution of temperature gradient in the vertical direction of the
      investigated volume of water leads to the abnormal large change in the value of
      water conductance. It was also shown, that the contact with atmosphere is not a
      determining factor for the existence of the observed phenomenon.

PMID- 25868360
TI  - [Systems with a concentration gradient have no potential energy but have the
      ability to do useful work].
AB  - The systems with the concentration gradient have no potential energy for heat and
      useful work production. Nevertheless, they have the ability to do useful work due
      to the heat dragged from the environment using, for instance, electrodes in the
      concentration cells. The second law of thermodynamics is not violated: work
      process occurred due to the heat dragged from the environment is coupled with the
      process of concentration leveling.

PMID- 25868361
TI  - [It is easy to see but it is difficult to foresee. To the 80th-annivesary of
      Elena Borisovna Burlakova].

PMID- 25868362
TI  - [Clinical and anatomical conferences, their place and importance in the hospital
      work system].

PMID- 25868363
TI  - [Further investigation of rhabdomyomas from myoblasts].

PMID- 25868364
TI  - [Age-related morphological changes in the aortic wall in dissecting aneurysm].
AB  - OBJECTIVE: To reveal the morphological features of the aorta in its dissection in
      persons of different age groups. MATERIAL AND METHODS: The operative material
      obtained after resection of the aorta for its dissection was examined. The
      fragments of the wall of the ascending aorta were fixed in 10% formalin solution
      immediately following its resection. The material was treated by processing and
      fixing methods; paraffin sections were stained with hemotoxyllin-eosin, orsein by
      the Van-Gieson, MSB, and Leigh methods. RESULTS: By analyzing 77 dissecting
      aortic aneurysm biopsy specimens, the authors presented the structural features
      of the aortic wall in terms of age-related changes. Examinations were made by
      light and electron microscopy using special stains. The signs of physiological or
      premature aging were assessed by elastic skeleton changes. There was a deficiency
      of collagen and its impaired maturation in all the study cases of vascular aging
      in the presence of aortic dissection. CONCLUSION: Quantitative and qualitative
      changes in the smooth muscle cells were due to both patient age and concomitant
      hypertension. In young patients, aortic dissection was more frequently caused by
      a genetically determined disorder in the elastic skeleton in obvious substitutive
      sclerosis.

PMID- 25868365
TI  - [Pulmonary histological and ultrastructural changes in HIV infection concurrent
      with tuberculosis].
AB  - OBJECTIVE: To analyze cellular and subcellular disorders in the lung in the
      presence of HIV-associated tuberculosis. MATERIAL AND METHODS: The investigators
      made a comprehensive morphological examination of 25 autopsy specimens from
      patients who had died from HIV-associated tuberculosis. Lung pieces from the foci
      of caseous necrosis at its boundary and adjacent lung segments and from
      macroscopically intact perifocal pulmonary segments were microscopically
      explored. Plain stains and Ziehl-Neelsen histobacterioscopy were used for light
      microscopy. An immunohistochemical study was conducted using tuberculosis mouse
      monoclonal antibodies (clone 1.1/3/1, Vector). Seven early autopsy specimens (1-2
      hours after statement of biological death) were investigated ultrastructurally.
      Ultrathin sections were contrasted with Reynolds' lead citrate and looked through
      a Libra-120 transmission electron microscope (Germany). Semithin sections were
      stained with toluidine blue. RESULTS: HIV-associated tuberculosis is a disease
      accompanied by dual aggressive infection. Impaired blood-air barrier integrity
      gives rise to structural and ultrastructural changes primarily in type I
      alveolocytes that are responsible for physiological gas exchange and
      detoxification. Type I alveolocytes have been noted to be in close contact with
      plasmocytes that are most ultrastructurally preserved and at the same time
      display the phagocytic and detoxifying functions being redistributed, which is
      necessary to keep cells viable and which is a characteristic sign of this
      comorbidity. This redistribution is due to severe damage to macrophages that are
      unable to ensure complete mycobacterial phagocytosis; thereby the plasma cells
      partly assume this function, as supported by ultrastructural examination. Severe
      destruction of granulocyte organelles and partial and complete cell necrosis with
      its preceding apoptotic changes were established. A study of vessels in the
      microcirculatory bed has indicated that the ultrastructural changes in the
      endothelial cells are polymorphic, which is characteristic of an exudative
      inflammatory response of lung tissue. CONCLUSION: Cellular and subcellular
      changes, the pattern of intercellular relationships, and necrotic and apoptotic
      cell rearrangements, which are in one way or another involved in the
      pathophysiological processes maintaining definite hemostasis, are an important
      component in the pathogenesis of HIV-associated tuberculosis.

PMID- 25868366
TI  - [The morphology of vocal fold polyps and mucosa in Reinke's edema].
AB  - OBJECTIVE: To investigate the morphogenesis of vocal fold polyps and Reinke's
      edema on the basis of clinical and morphological analyses of the histological and
      immunohistochemical data characterizing the state of the local microcirculatory
      bed and the mechanisms of its permeability impairment. SUBJECTS AND METHODS:
      Polyps of the vocal folds and their mucosal tissue samples in Reinke's edema
      mucosa, which had been obtained after microsurgical treatment of 31 patients (13
      men and 18 women) aged 23 to 75 years, were studied using a wide panel of
      peroxidase-labeled monoclonal and polyclonal antibodies (DAB chromogen),
      including T and B cell differentiation markers, Toll-like receptors (TLR2, TLR4,
      and TLR9), the costimulatory molecule CD80 (B7- 1), and markers for angiogenesis
      (CD34), vascular and tissue permeability (matrix metalloproteinases (MMP-1 and
      MMP-9)), and vascular cell adhesion molecule-1 (VCAM-1). Results. All types of
      the examined polypoid hyperplasia were ascertained to realize through the
      impaired permeability of the wall of microcirculatory vessels in the membranous
      vocal fold portion called Reinke's space. The expression of molecules, such as
      CD34, VCAM-1, MMP-1 and MMP-9, as well as TLR4 and TLR9 was revealed on the
      endothelial cells of microcirculatory vessels. The epithelial lining cells
      simultaneously expressed the above-mentioned Toll-like receptors and the
      costimulatory molecule CD80 (B7-1) that modulated T cell lymphocyte activity
      (through CD28) or attenuation (through CTLA-4), ensuring the interaction of
      structures of innate and adaptive immunity. CONCLUSION: The morphogenesis of
      polypoid hyperplasia of the vocal folds is a result of an epithelial stromal
      interaction under poor etiological factors, such as high vocal loads, exogenic
      intoxications, and viral infections. The integumentary lining cells carrying Toll
      like receptors initiate reactive alterations in Reinke's space.

PMID- 25868367
TI  - [The immunohistochemical features of ovarian serous adenocarcinoma cells, which
      determine a disease course and survival rates in patients].
AB  - OBJECTIVE: To study a relationship of survival rates to the expression of major
      genes (p53, PTEN, COX2, pRb and others) involved in the pathogenesis of ovarian
      cancer. SUBJECTS AND METHODS: The trial enrolled 23 patients with Stages III-IV
      ovarian serous adenocarcinoma. Of them, 11 patients showed a long overall
      survival (median 50 +/- 2.5 months), 12 did a short one (14.5 +/- 0.7 months).
      Ovarian adenocarcinomas were high- and low-grade in 20 (87%) and 3 (13%) cases,
      respectively. RESULTS: Estimating the relationship of the expression of the
      examined markers and the prognosis of the disease showed that the expression of
      p53 and Rb was more common in the patients with a short overall survival (median
      14.5 versus 50 months; p = 0.03; p = 0.04). CONCLUSION: The expression of mutant
      p53 protein and that of retinoblastoma (Rb) gene protein are poor prognostic
      factors for ovarian serous adenocarcinoma.

PMID- 25868368
TI  - [Inhibition of matrix metalloproteinases 9 and 13 affects the degree of
      lymphocytic infiltration and the expression levels of microRNA miR-21 and miR-let
      7b in melanoma cells in vivo].
AB  - OBJECTIVE: To estimate changes in the trend of growth of primary tumor nodules,
      the degree of lymphocytic infiltration, and the expression levels of oncomicroRNA
      miR-21 and miR-let-7b when inhibiting matrix metalloproteinases 9 and 13 (MMP-9
      and MMP-13) in vivo in C57B16 mice with transplantable melanoma B-16. MATERIAL
      AND METHODS: Tumor growth was evaluated measuring the volume of primary tumor
      nodules; the degree of lymphocytic infiltration was microscopically estimated
      using hematoxylin-eosin-stained tissue specimens, by calculating intratumoral
      lymphocytes. The expression of oncomicroRNA was quantified by real-time PCR.
      RESULTS: It was shown that MMP-9 and MMP-13 inhibition had no impact on the
      growth of primary tumor nodules; selective MMP-9 inhibition failed to affect the
      degree of lymphocytic infiltration of a primary tumor nodule and to change the
      expression of oncomicroRNA miR-21 and miR-let-7b; the concomitant inhibition of
      MMP-9 and MMP-13 altered the immunogenic properties of melanoma, stimulated the
      lymphocytic infiltration of tumor nodules, and decreased the expression of
      oncomicroRNA miR-21 and miR-let-7b; the degree of lymphocytic infiltration of
      primary tumor nodules increased in the dynamics of a tumor process and the
      expression levels of oncomicroRNA remained unchanged. CONCLUSION: The concomitant
      inhibition of MMP-9 and MMP-13 affects prognosis and survival in skin melanoma.

PMID- 25868369
TI  - [Changes in the WHO classification of soft tissue tumors].
AB  - This article reviews key changes in the current 2013 World Health Organization
      Classification of soft tissue tumors.

PMID- 25868370
TI  - [Adrenocortical oncocytoma].
AB  - The paper characterizes adrenocortical oncocytoma, a rare adrenal tumor,
      accompanied by Cushing's syndrome and estrogen and androgen production and
      provides histological and immunohistochemical features. The authors describe
      their observation of a 33-year-old female woman. It is shown that estimation of
      the malignant potential of adrenocortical oncocytomas requires a special approach
      and must be done using the Lin-Weiss-Bisceglia criteria.

PMID- 25868371
TI  - [Serrated lesions of the large bowel].
AB  - The 2010 WHO classification identifies a new group of pretumor lesions of the
      large bowel--serrated masses, which includes hyperplastic polyps (HPs), sessile
      serrated adenomas/polyps (SSA/P), and traditional serrated adenomas (TSA).
      Serrated masses are a heterogeneous group characterized by serrated gland lumens
      and, in most cases, without dysplasia. An enlarged proliferative zone, elongated
      crypts, and no cytological atypia in addition to a serrated lumen are typical of
      HPs. SSA/P is characterized by the migration of the proliferative zone to the
      crypt walls, giving rise to specific architectural disorders, such as expanded
      and horizontally growing basal gland segments along the lamina muscularis
      mucosae. TSA is typified by short ectopic crypts that cannot reach the lamina
      muscularis and by epithelial eosinophilic changes. SSA/P and TSA have peculiar
      molecular genetic profiles and proven malignant potential.

PMID- 25868372
TI  - [High-grade prostatic intraepithelial neoplasia: state-of-the-art].
AB  - According to current views, high-grade prostatic intraepithelial neoplasia is the
      most likely precursor of prostate adenocarcinoma. This review gives the latest
      data of genetic, proteomic, and morphological analyses of this neoplasia and
      touches upon the probems that might arise when searching for new markers for
      differential diagnosis and prognosis estimation.

PMID- 25868373
TI  - [Epithelial-mesenchymal transition in health and disease].
AB  - The paper gives general information about the epithelial-mesenchymal transition
      (EMT), its morphological manifestations, altered expression of a number of
      proteins, types of EMT, and its role in embryogenesis and human diseases,
      including that about EMT as a mechanism by which the tumor cell acquires
      prometastatic potential. EMT is a process that is essential in health for
      gastrulation and the formation of neural crest cells; however, it is also
      important for the development of abnormalities, among other processes, organ
      fibrosis and tumor metastases. An understanding of the role of EMT in cancer
      spread has led to active studies of the process in the past decades. Despite the
      fact that there are sufficiently many publications on different aspects of EMT,
      the exact mechanisms regulating the process and the possibility for its
      therapeutic exposure remain unclear. There is also evidence on the possible
      association of EMT with the generation of cancer stem cells in tumors.

PMID- 25868374
TI  - [Aleksey Ivanovich Abrikosov: his life devoted to pathological anatomy (on the
      occasion of the 140th anniversary of his birth)].

PMID- 25868375
TI  - [Who could reconcile the irreconcilable (on the occasion of the 150th anniversary
      of Nicolaas Philip Tendeloo birth)].

PMID- 25868376
TI  - Characterization of the toxicological hazards of hydrocarbon solvents.
AB  - Hydrocarbon solvents are liquid hydrocarbon fractions derived from petroleum
      processing streams, containing only carbon and hydrogen atoms, with carbon
      numbers ranging from approximately C5-C20 and boiling between approximately 35
      370 degrees C. Many of the hydrocarbon solvents have complex and variable
      compositions with constituents of 4 types, alkanes (normal paraffins,
      isoparaffins, and cycloparaffins) and aromatics (primarily alkylated one- and two
      ring species). Because of the compositional complexity, hydrocarbon solvents are
      now identified by a nomenclature ("the naming convention") that describes them in
      terms of physical/chemical properties and compositional elements. Despite the
      compositional complexity, most hydrocarbon solvent constituents have similar
      toxicological properties, and the overall toxicological hazards can be
      characterized in generic terms. To facilitate hazard characterization, the
      solvents were divided into 9 groups (categories) of substances with similar
      physical and chemical properties. Hydrocarbon solvents can cause chemical
      pneumonitis if aspirated into the lung, and those that are volatile can cause
      acute CNS effects and/or ocular and respiratory irritation at exposure levels
      exceeding occupational recommendations. Otherwise, there are few toxicologically
      important effects. The exceptions, n-hexane and naphthalene, have unique
      toxicological properties, and those solvents containing constituents for which
      classification is required under the Globally Harmonized System (GHS) are
      differentiated by the substance names. Toxicological information from studies of
      representative substances was used to fulfill REACH registration requirements and
      to satisfy the needs of the OECD High Production Volume (HPV) initiative. As
      shown in the examples provided, the hazard characterization data can be used for
      hazard classification and for occupational exposure limit recommendations.

PMID- 25868377
TI  - Targeted next-generation sequencing for the genetic diagnosis of dysferlinopathy.
AB  - Dysferlinopathy comprises a group of autosomal recessive muscular dystrophies
      caused by mutations in the DYSF gene. Due to the large size of the gene and its
      lack of mutational hot spots, analysis of the DYSF gene is time-consuming and
      laborious using conventional sequencing methods. By next-generation sequencing
      (NGS), DYSF gene analysis has previously been validated through its incorporation
      in multi-gene panels or exome analyses. However, individual validation of NGS
      approaches for DYSF gene has not been performed. Here, we established and
      validated a hybridization capture-based target-enrichment followed by next
      generation sequencing to detect mutations in patients with dysferlinopathy. With
      this approach, mean depth of coverage was approximately 450 fold and almost all
      (99.3%) of the targeted region had sequence coverage greater than 20 fold. When
      this approach was tested on samples from patients with known DYSF mutations, all
      known mutations were correctly retrieved. Using this method on 32 consecutive
      patient samples with dysferlinopathy, at least two pathogenic variants were
      detected in 28 (87.5%) samples and at least one pathogenic variant was identified
      in all samples. Our results suggested that the NGS-based screening method could
      facilitate efficient and accurate genetic diagnosis of dysferlinopathy. 

PMID- 25868378
TI  - [A particular type of herpetic keratitis: Archipelago keratitis].

PMID- 25868379
TI  - Nonarteritic anterior ischemic optic neuropathy in young patients.
AB  - PURPOSE: To determine and report the demographic and clinical features of
      patients younger than 50 years with nonarteritic anterior ischemic optic
      neuropathy (NAION). MATERIAL AND METHODS: In this comparative study, we
      retrospectively reviewed the medical records of 120 patients with NAION. Patients
      were divided into two groups according to their age; in group I, 44 patients were
      younger than 50 years, and in group II, 76 patients were older than 50 years.
      RESULTS: The gender distribution was similar in both main groups. Involvement was
      bilateral in 50% and 26.3% of patients, respectively (P<0.0001). Diabetes
      mellitus was present in 63.6% of patients in group I and 47.3% of patients in
      group II (P=0.009). We found hypertension as a frequent risk factor in group II
      (P=0.019). There was no significant difference in the initial and final visual
      acuities of patients between the two groups. Both groups had a significantly
      thinner peripapillary nerve fiber layer (RNFL) in every quadrant. The relative
      loss was greatest in the superior quadrant in both groups. We generally observed
      inferior altitudinal defect and superior RNFL thinning in two groups. In group I,
      30 eyes (68.1%) demonstrated angiographically diffuse optic disc filling delay of
      >=5seconds after choroidal filling confirming ischemia, and 14 (31.8%) eyes with
      segmental optic disc filling delay. In group II, diffuse optic disc filling delay
      was seen in 56 of 76 (73.6%) eyes. Segmental optic disc filling delay was present
      in 20 eyes (26.3%). There was no significant difference in angiographic findings
      between the two groups (P=0.67). CONCLUSION: We observed that age did not play a
      significant role in prognosis of NAION. Diabetes is an increased risk for NAION
      in the young age group, and HT for NAION in the older group. Fellow eye
      involvement is more frequent in young patients. These patients should be followed
      closely.

PMID- 25868380
TI  - New Editor-in-Chief of the International Journal for Parasitology.

PMID- 25868382
TI  - Sallimus and the dynamics of sarcomere assembly in Drosophila flight muscles.
AB  - The Drosophila indirect flight muscles (IFM) can be used as a model for the study
      of sarcomere assembly. Here we use a transgenic line with a green fluorescent
      protein (GFP) exon inserted into the Z-disc-proximal portion of sallimus (Sls),
      also known as Drosophila titin, to observe sarcomere assembly during IFM
      development. Firstly, we confirm that Sls-GFP can be used in the heterozygote
      state without an obvious phenotype in IFM and other muscles. We then use Sls-GFP
      in the IFM to show that sarcomeres grow individually and uniformly throughout the
      fibre, growing linearly in length and in diameter. Finally, we show that limiting
      the amounts of Sls in the IFM using RNAi leads to sarcomeres with smaller Z-discs
      in their core, whilst the thick/thin filament lattice can form peripherally
      without a Z-disc. Thick filament preparations from those muscles show that
      although the Z-disc-containing core has thick filaments of a regular length,
      filaments from the peripheral lattice are longer and asymmetrical around the bare
      zone. Therefore, the Z-disc and Sls are required for thick filament length
      specification but not for the assembly of the thin/thick filament lattice. 

PMID- 25868384
TI  - Experimental and theoretical studies on aqueous-phase reactivity of hydroxyl
      radicals with multiple carboxylated and hydroxylated benzene compounds.
AB  - In this study, we shed light on the initial addition of hydroxyl radicals (HO) to
      multiple carboxylated and hydroxylated benzene compounds in aqueous-phase
      advanced oxidation processes (AOPs). We analyze the experimentally measured
      transient spectra near neutral pH using quantum mechanical-based time-dependent
      density functional theory (TD-DFT). The ab initio DFT method was first used to
      find and optimize aqueous-phase transition state structures, then the TD-DFT was
      used to analyze molecular orbitals (MOs) of the optimized transition state
      structures to reveal the functional groups that are responsible for the
      individual absorption peaks. The initial addition of HO to the benzene ring
      produced hydroxycyclohexadienyl radicals. Then, HO-adducts are generated from
      dimerization or disproportionation of hydroxycyclohexadienyl radicals and
      represent their transient spectral peaks at approximately 350 nm and 250 nm. As
      reaction proceeds, the HO-adducts are decreased depending on the subsequent
      reactions. These investigations into the experimental transient spectra coupled
      with the theoretical analysis using the TD-DFT enable us to visualize an initial
      transformation of organic compounds induced by the aqueous phase HO oxidation.
      Moreover, the experimental reaction rate constants and the theoretically
      calculated aqueous phase free energies of activation provide quantitative
      insights into the addition of HO to multiple carboxylated and hydroxylated
      benzene compounds. 

PMID- 25868381
TI  - Molecular sensors and modulators of thermoreception.
AB  - The detection of temperature is one of the most fundamental sensory functions
      across all species, and is critical for animal survival. Animals have thus
      evolved a diversity of thermosensory mechanisms allowing them to sense and
      respond to temperature changes (thermoreception). A key process underlying
      thermoreception is the translation of thermal energy into electrical signals, a
      process mediated by thermal sensors (thermoreceptors) that are sensitive to a
      specific range of temperatures. In disease conditions, the temperature
      sensitivity of thermoreceptors is altered, leading to abnormal temperature
      sensation such as heat hyperalgesia. Therefore, the identification of thermal
      sensors and understanding their functions and regulation hold great potential for
      developing novel therapeutics against many medical conditions such as pain. 

PMID- 25868383
TI  - Atomic-Resolution Structures of Discrete Stages on the Reaction Coordinate of the
      [Fe4S4] Enzyme IspG (GcpE).
AB  - IspG is the penultimate enzyme in non-mevalonate biosynthesis of the universal
      terpene building blocks isopentenyl diphosphate and dimethylallyl diphosphate.
      Its mechanism of action has been the subject of numerous studies but remained
      unresolved due to difficulties in identifying distinct reaction intermediates.
      Using a moderate reducing agent and an epoxide substrate analogue, we were now
      able to trap and crystallographically characterize various stages in the IspG
      catalyzed conversion of 2-C-methyl-D-erythritol-2,4-cyclo-diphosphate into (E)-1
      hydroxy-2-methylbut-2-enyl-4-diphosphate. In addition, the enzyme's structure was
      determined in complex with several inhibitors. These results, combined with
      recent electron paramagnetic resonance data, allowed us to deduce a detailed and
      complete IspG catalytic mechanism, which describes all stages from initial ring
      opening to formation of (E)-1-hydroxy-2-methylbut-2-enyl-4-diphosphate via
      discrete radical and carbanion intermediates. The data presented in this article
      provide a guide for the design of selective drugs against many prokaryotic and
      eukaryotic pathogens to which the non-mevalonate pathway is essential for
      survival and virulence.

PMID- 25868385
TI  - "Knife to skin" time is a poor marker of operating room utilization and
      efficiency in cardiac surgery.
AB  - BACKGROUND: Markers of operation room (OR) efficiency in cardiac surgery are
      focused on "knife to skin" and "start time tardiness." These do not evaluate the
      middle and later parts of the cardiac surgical pathway. The purpose of this
      analysis was to evaluate knife to skin time as an efficiency marker in cardiac
      surgery. METHODS: We looked at knife to skin time, procedure time, and transfer
      times in the cardiac operational pathway for their correlation with predefined
      indices of operational efficiency (Index of Operation Efficiency - InOE, Surgical
      Index of Operational Efficiency - sInOE). A regression analysis was performed to
      test the goodness of fit of the regression curves estimated for InOE relative to
      the times on the operational pathway. RESULTS: The mean knife to skin time was
      90.6 +/- 13 minutes (23% of total OR time). The mean procedure time was 282 +/-
      123 minutes (71% of total OR time). Utilization efficiencies were highest for
      aortic valve replacement and coronary artery bypass grafting and least for
      complex aortic procedures. There were no significant procedure-specific or team
      specific differences for standard procedures. Procedure times correlated the
      strongest with InOE (r = -0.98, p < 0.01). Compared to procedure times, knife to
      skin is not as strong an indicator of efficiency. A statistically significant
      linear dependence on InOE was observed with "procedure times" only. CONCLUSIONS:
      Procedure times are a better marker of OR efficiency than knife to skin in
      cardiac cases. Strategies to increase OR utilization and efficiency should
      address procedure times in addition to knife to skin times.

PMID- 25868386
TI  - Poly-autoimmunity in patients with myasthenia gravis: A single-center experience.
AB  - We evaluated the co-occurrence of autoimmune diseases (ADs) in a large population
      of myasthenia gravis (MG) patients from a single center. Our survey included 984
      patients, 904 with anti-acetylcholine receptor antibodies and 80 with anti-muscle
      specific kinase antibodies. The anti-acetylcholine receptor positive population
      included patients with early-onset (age at onset <= 50 years), late-onset and
      thymoma-associated disease. Follow-up ranged 2-40 years. Two-hundred and fourteen
      ADs were diagnosed in 185 patients; 26 of them had two or more ADs in association
      with MG. Thyroid disorders were the most common and, together with vitiligo and
      thrombocytopenia, occurred in all disease subsets. Otherwise, there was a broad
      variability with partial overlap among patient groups. The highest rate of ADs
      was observed in early-onset patients, while clusters, i.e. 2 or more ADs other
      than MG in the same individual, were more common among thymoma cases. Thirty-four
      diseases were diagnosed at the same time, 88 occurred before and 92 after the
      onset of MG. On multivariate analysis, immunosuppressive treatment was the only
      independent variable which negatively influenced the risk of developing other ADs
      in our cohort.

PMID- 25868387
TI  - The association between rs4684677 T/A polymorphism in preproghrelin gene and
      predisposition to autoimmune thyroid diseases in children.
AB  - BACKGROUND: A potential role of preproghrelin polymorphisms on autoimmune thyroid
      diseases (AITDs) has not been established equivocally yet. AIM: To estimate the
      association of two polymorphisms of preproghrelin gene with the predisposition to
      Graves' disease (GD) and Hashimoto's thyroiditis (HT) in children. METHODS: The
      study was performed in 145 patients with GD, 87 with HT and 161 healthy
      volunteers. The two single nucleotide polymorphisms (SNPs) rs696217
      (C_3151003_20) and rs4684677 (C_25607748_10) in the preproghrelin gene were
      genotyped by TaqMan SNP genotyping assay using the real-time PCR. RESULTS:
      Rs4684677 T alleles were more frequent in HT patients (99% in women and 100% in
      men) in comparison to healthy subjects (p = 0.002) with OR = 8.0 and 95%
      confidence interval for OR: 1.8-206.7. In women group, rs4684677 T alleles were
      more frequent compared to healthy controls (99%) in HT (p = 0.02) with OR = 6.7
      and 95% confidence interval for OR: 1.2-168.37. Frequency of the SNP rs696217 did
      not differ between the groups. There was a significant relationship between
      rs696217 polymorphisms and anti-TSHR antibodies level (p = 0.036) in women from
      GD/HT groups. A significant relationship between rs696217 polymorphisms and anti
      TG antibodies level in GD women group (p = 0.038) and between rs696217
      polymorphisms and fT4 concentration (p = 0.03) were found. CONCLUSIONS: Rs4684677
      T/A polymorphisms in preproghrelin gene could contribute to development of AITDs
      in children and T allele is the main risk factor.

PMID- 25868388
TI  - Yes-mediated phosphorylation of focal adhesion kinase at tyrosine 861 increases
      metastatic potential of prostate cancer cells.
AB  - To study the role of FAK signaling complexes in promoting metastatic properties
      of prostate cancer (PCa) cells, we selected stable, highly migratory variants,
      termed PC3 Mig-3 and DU145 Mig-3, from two well-characterized PCa cell lines, PC3
      and DU145. These variants were not only increased migration and invasion in
      vitro, but were also more metastatic to lymph nodes following intraprostatic
      injection into nude mice. Both PC3 Mig-3 and DU145 Mig-3 were specifically
      increased in phosphorylation of FAK Y861. We therefore examined potential
      alterations in Src family kinases responsible for FAK phosphorylation and
      determined only Yes expression was increased. Overexpression of Yes in PC3
      parental cells and src-/-fyn-/-yes-/- fibroblasts selectively increased FAK Y861
      phosphorylation, and increased migration. Knockdown of Yes in PC3 Mig-3 cells
      decreased migration and decreased lymph node metastasis following orthotopic
      implantation of into nude mice. In human specimens, Yes expression was increased
      in lymph node metastases relative to paired primary tumors from the same patient,
      and increased pFAK Y861 expression in lymph node metastases correlated with poor
      prognosis. These results demonstrate a unique role for Yes in phosphorylation of
      FAK and in promoting PCa metastasis. Therefore, phosphorylated FAK Y861 and
      increased Yes expression may be predictive markers for PCa metastasis. 

PMID- 25868391
TI  - Correction to alpha2-Adrenoceptor Antagonists: Synthesis, Pharmacological
      Evaluation, and Molecular Modeling Investigation of Pyridinoguanidine, Pyridino-2
      aminoimidazoline and Their Derivatives.

PMID- 25868389
TI  - Identification of new biomarkers for human papillary thyroid carcinoma employing
      NanoString analysis.
AB  - We previously reported an upregulation of the clock transcript BMAL1, correlating
      with TIMP1 expression in fresh-frozen samples from papillary thyroid carcinoma
      (PTC). Since frozen postoperative biopsy samples are difficult to obtain, we
      aimed to validate the application of high-precision NanoString analysis for
      formalin-fixed paraffin-embedded (FFPE) thyroid nodule samples and to screen for
      potential biomarkers associated with PTC. No significant differences were
      detected between fresh-frozen and FFPE samples. NanoString analysis of 51
      transcripts in 17 PTC and 17 benign nodule samples obtained from different donors
      and in 24 pairs of benign and PTC nodules, obtained from the same donor
      (multinodular goiters), confirmed significant alterations in the levels of BMAL1,
      c-MET, c-KIT, TIMP1, and other transcripts. Moreover, we identified for the first
      time alterations in CHEK1 and BCL2 levels in PTC. A predictive score was
      established for each sample, based on the combined expression levels of BMAL1,
      CHEK1, c-MET, c-KIT and TIMP1. In combination with BRAF mutation analysis, this
      predictive score closely correlated with the clinicopathological characteristics
      of the analyzed thyroid nodules. Our study identified new thyroid transcripts
      with altered levels in PTC using the NanoString approach. A predictive score
      correlation coefficient might contribute to improve the preoperative diagnosis of
      thyroid nodules. 

PMID- 25868390
TI  - Low thyroid hormone levels improve survival in murine model for ocular melanoma.
AB  - Uveal melanoma is highly metastatic, prognosis is poor and there are no effective
      treatments to extend survival. Accumulating evidence suggests that thyroid
      hormones have a mitogenic effect via binding to alphavbeta3 integrin. We aimed to
      examine the impact of thyroid status on survival in a murine B16F10 model for
      ocular melanoma, highly expressing the integrin. In two independent experiments
      oral propylthiouracil (PTU) was used to induce hypothyroidism (n=9), thyroxine to
      induce hyperthyroidism (n=11) and mice given plain water served as control (n=8).
      At day 21, the subretinal space was inoculated with 10(2) B16F10 cells. In non
      inoculated mice (n=6 of each group) serum free T4 (FT4) levels were measured and
      additional non-inoculated mice (3 given PTU and 4 given thyroxine or water)
      served as internal control to demonstrate the impact of the dissolved substance.
      The PTU-inoculated mice showed clinical evidence of intraocular tumor growth
      significantly later than the thyroxine mice (P=0.003) and survival time was
      significantly longer (P<0.001). FT4 levels differed significantly between groups
      (P<0.001) and with no signs of illness in the internal control group. Our
      findings suggest that hyperthyroidism shortens survival, whereas relative
      hypothyroidism may have a protective role in metastatic ocular melanoma.

PMID- 25868392
TI  - Epilepsy: closing the loop for patients with epilepsy.
AB  - In a long-term clinical trial, a responsive neurostimulation system was shown to
      reduce seizures and improve quality of life in patients with drug-resistant
      epilepsy. Furthermore, these effects persisted over an extended time period. Will
      neurostimulation close the treatment gap for patients with refractory epilepsy?

PMID- 25868393
TI  - Multiple sclerosis: Genetic variability affects CNS IgG production in MS.

PMID- 25868394
TI  - On the relation of energy and electron transfer in multidimensional chromophores
      based on polychlorinated triphenylmethyl radicals and triarylamines.
AB  - A star-like compound consisting of a polychlorinated triphenylmethyl radical
      (PCTM) core linked to three triarylamines (TAA) and a symmetric and an asymmetric
      hexaarylbenzene (HAB) both substituted with three PCTMs and three TAAs were
      synthesised. In the star-like compound a strong communication between the redox
      centres was observed by electron paramagnetic resonance spectroscopy and
      UV/Vis/NIR absorption measurements, whereas in the HABs only a weak interaction
      could be detected. The temporal evolution of the excited states was monitored by
      ultrafast transient absorption measurements. Within the first picosecond
      stabilisation of the charge transfer state was observed induced by solvent
      rotation. Anisotropic transient absorption measurements revealed that within the
      lifetime of the excited state (tau = 1-4 ps) energy transfer does not occur in
      the HABs whereas in the star-like system ultrafast and possibly coherent energy
      redistribution is observed. Taken this information together we made the identity
      between energy transfer and electron transfer in the specific systems apparent. 

PMID- 25868395
TI  - Influence of temperature on nucleus degradation of 4-androstene-3, 17-dione in
      phytosterol biotransformation by Mycobacterium sp.
AB  - One of the steroid intermediates, 4-androstene-3, 17-dione (AD), in the
      biotransformation of phytosterols is valuable for the production of steroid
      medicaments. However, its degradation during the conversion process is one of the
      main obstacles to obtain high yields. In this study, the effect of temperature on
      nucleus degradation during microbial biotransformation of phytosterol was
      investigated. The results indicated that microbial degradation of phytosterol
      followed the AD-ADD-'9-OH-ADD' pathway, and that two important reactions involved
      in nucleus degradation, conversions of AD to ADD and ADD to 9-OH-ADD, were
      inhibited at 37 degrees C. With a change in the culture temperature from 30 to 37
      degrees C, nucleus degradation was reduced from 39.9% to 17.6%, due to inhibition
      of the putative KstD and Ksh. These results suggested a simple way to decrease
      the nucleus degradation in phytosterol biotransformation and a new perspective on
      the possibilities of modifying the metabolism of strains used in industrial
      applications. SIGNIFICANCE AND IMPACT OF THE STUDY: Nucleus degradation of
      products is one of the main problems encountered during phytosterol
      biotransformation. To solve this problem, the effect of temperature on nucleus
      degradation was investigated in the industrial production of steroid
      intermediates. The results are also helpful to the genetic modification of sterol
      producing strains.

PMID- 25868396
TI  - Aging without Apolipoprotein D: Molecular and cellular modifications in the
      hippocampus and cortex.
AB  - A detailed knowledge of the mechanisms underlying brain aging is fundamental to
      understand its functional decline and the baseline upon which brain pathologies
      superimpose. Endogenous protective mechanisms must contribute to the adaptability
      and plasticity still present in the healthy aged brain. Apolipoprotein D (ApoD)
      is one of the few genes with a consistent and evolutionarily conserved up
      regulation in the aged brain. ApoD protecting roles upon stress or injury are
      well known, but a study of the effects of ApoD expression in the normal aging
      process is still missing. Using an ApoD-knockout mouse we analyze the effects of
      ApoD on factors contributing to the functional maintenance of the aged brain. We
      focused our cellular and molecular analyses in the cortex and hippocampus at an
      age representing the onset of senescence where mortality risks are below 25%,
      avoiding bias towards long-lived animals. Lack of ApoD causes a prematurely aged
      brain without altering lifespan. Age-dependent hyperkinesia and memory deficits
      are accompanied by differential molecular effects in the cortex and hippocampus.
      Transcriptome analyses reveal distinct effects of ApoD loss on the molecular age
      dependent patterns of the cortex and hippocampus, with different cell-type
      contributions to age-regulated gene expression. Markers of glial reactivity,
      proteostasis, and oxidative and inflammatory damage reveal early signs of aging
      and enhanced brain deterioration in the ApoD-knockout brain. The lack of ApoD
      results in an age-enhanced significant reduction in neuronal calcium-dependent
      functionality markers and signs of early reduction of neuronal numbers in the
      cortex, thus impinging upon parameters clearly differentiating neurodegenerative
      conditions from healthy brain aging. Our data support the hypothesis that the
      physiological increased brain expression of ApoD represents a homeostatic anti
      aging mechanism. 

PMID- 25868397
TI  - Association between leukocyte telomere length and bone mineral density in women
      25-93 years of age.
AB  - Leukocyte telomere length (LTL) and bone mineral density (BMD) are associated
      with health and mortality. Because osteoporosis is an age-related condition and
      LTL is considered to be a biomarker of aging, we hypothesized that shorter LTL
      could predict lower BMD. The aim of our study was to assess whether there is an
      association of LTL with BMD and to determine whether this possible association is
      independent of age. The BMDs of the lumbar spine (LS), femoral neck (FN) and
      total hip (TH) were evaluated in 460 women using DXA. LTL was analyzed using
      quantitative polymerase chain reaction. The women completed a health and
      lifestyle questionnaire. The associations were estimated by regression models
      that considered age, body mass index (BMI), menopause, physical activity, alcohol
      consumption and smoking habits. We found a statistically significant unadjusted
      association between LTL and age (estimate and 95% confidence interval (CI): 
      0.003 (-0.005; -0.002)); and between BMI adjusted age and logarithmic transformed
      BMD. Estimates and 95% CI were as follows: LS: -0.13 (-0.26; -0.01); right TH: 
      0.44 (-0.53; -0.34); left TH: -0.38 (-0.48; -0.28); right FN: -0.57 (-0.67; 
      0.46) and left FN: -0.51 (-0.62; -0.40). There were no statistically significant
      associations between BMD and LTL (both logarithmically transformed) with or
      without age adjustments. The age-adjusted estimates and CI were as follows: LS: 
      0.10 (-0.71; 0.52); right TH: -0.13 (-0.66; 0.41); left TH: -0.13 (-0.67; 0.42);
      right FN: -0.03 (-0.58; 0.52) and left FN: 0.09 (-0.47; 0.66). In conclusion, we
      found no statistically significant associations between BMD and LTL, although the
      estimates of the crude associations were all positive, indicating hypothesis
      consistency; that shorter LTL predict lower BMD values. This positive association
      was no longer apparent after adjusting for age. As expected, age was
      statistically significantly associated with both telomere length and BMI adjusted
      BMD. 

PMID- 25868398
TI  - Selective gas diffusion in graphene oxides membranes: a molecular dynamics
      simulations study.
AB  - Designing membrane materials from one-atom-thick structures is highly promising
      in separation and filtration applications for the reason that they offer the
      ultimate precision in modifying the atomic structures and chemistry for
      optimizing performance, and thus resolving the permeation-selectivity trade-off.
      In this work, we explore the molecular dynamics of gas diffusion in the gallery
      space between functionalized graphene layers as well as within nanopores across
      the multilayers. We have identified highly selective gas permeation that agrees
      with recent experimental measurements and is promising for advancing gas
      separation technologies such as hydrogen separation, helium/nitrogen generation,
      and CO2 sequestration. The roles of structural and chemical factors are discussed
      by considering different types of gases including H2, He, CH4, N2, O2, CO, CO2,
      and H2O. The overall performance of graphene oxide membranes is also discussed
      with respect to their microstructures, and compared with recent experimental
      measurements. These understandings could advise high-performance gas-separation
      membrane development by engineering assemblies of two-dimensional layered
      structures. 

PMID- 25868400
TI  - Modular Three-component Delivery System Facilitates HLA Class I Antigen
      Presentation and CD8(+) T-cell Activation Against Tumors.
AB  - Cell-mediated immunotherapies have potential as stand-alone and adjuvant
      therapies for cancer. However, most current protocols suffer from one or more of
      three major issues: cost, safety, or efficacy. Here we present a nanoparticle
      delivery system that facilitates presentation of an immunogenic measles antigen
      specifically in cancer cells. The delivery system does not contain viral
      particles, toxins, or biologically derived material. Treatment with this system
      facilitates activation of a secondary immune response against cancer cells,
      bypassing the need to identify tumor-associated antigens or educate the immune
      system through a primary immune response. The delivery system consists of a
      stealth liposome displaying a cancer-specific targeting peptide, named H1299.3,
      on its exterior surface and encapsulating H250, an immunogenic human leukocyte
      antigen class 1 restricted peptide. This targeted-nanoparticle facilitates
      presentation of the H250 peptide in major histocompatibility complex class I
      molecules. Activation is dependent on the targeting peptide, previous antigen
      exposure, and utilizes a novel autophagy-mediated mechanism to facilitate
      presentation. Treatment with this liposome results in a significant reduction of
      tumor growth using an aggressive LLC1 model in vaccinated C57BL/6 mice. These
      data provide proof-of-principle for a novel cell-mediated immunotherapy that is
      scalable, contains no biologically derived material, and is an efficacious cancer
      therapy. 

PMID- 25868401
TI  - Family visits in shared-housing arrangements for residents with dementia--a cross
      sectional study on the impact on residents' quality of life.
AB  - BACKGROUND: Shared-housing arrangements (SHA) are a German type of small-scale
      living arrangements for people with dementia (PwD). The involvement of family
      members is one core domain of SHA. But it has not been investigated yet, what are
      factors associated with family visits and if family involvement within SHA
      contributes to better residents' quality of life (QoL). METHOD: A cross-sectional
      study including all SHA in Berlin/Germany was performed. Main parameters of
      interest were residents' QoL (QUALIDEM) and frequencies of family visits within
      the SHA. Besides descriptive analyses we used logistic regression and ANCOVA to
      analyze the data. RESULTS: 58 SHA with 396 residents (78.4 years, 69.4% female)
      participated in the study. Older (OR: 1.034; 95% CI: 1.005; 1.064) and female
      residents (OR: 2.006; 95% CI: 1.018; 3.950) got more often visited by family
      members. An active participation of family members in SHA contributes on average
      to a better QoL in terms of social relationship and social isolation (all ANCOVA
      p < 0.005). A decreased QoL was found for people without family visits compared
      to those without family members. CONCLUSIONS: The involvement of family members
      in SHA is common but on a similar level compared to other care arrangements.
      Staff should convince available family members to visit PwD, in order to improve
      residents QoL. However, the response rate in the present study was about 13%,
      which may limit the results.

PMID- 25868399
TI  - Mesenchymal Stem Cell-derived Extracellular Vesicles: Toward Cell-free
      Therapeutic Applications.
AB  - Mesenchymal stem (stromal) cells (MSCs) are multipotent cells with the ability to
      differentiate into several cell types, thus serving as a cell reservoir for
      regenerative medicine. Much of the current interest in therapeutic application of
      MSCs to various disease settings can be linked to their immunosuppressive and
      anti-inflammatory properties. One of the key mechanisms of MSC anti-inflammatory
      effects is the secretion of soluble factors with paracrine actions. Recently it
      has emerged that the paracrine functions of MSCs could, at least in part, be
      mediated by extracellular vesicles (EVs). EVs are predominantly released from the
      endosomal compartment and contain a cargo that includes miRNA, mRNA, and proteins
      from their cells of origin. Recent animal model-based studies suggest that EVs
      have significant potential as a novel alternative to whole cell therapies.
      Compared to their parent cells, EVs may have a superior safety profile and can be
      safely stored without losing function. In this article, we review current
      knowledge related to the potential use of MSC-derived EVs in various diseases and
      discuss the promising future for EVs as an alternative, cell-free therapy. 

PMID- 25868402
TI  - Sex-Specificity in the Reward Value of Facial Attractiveness.
AB  - Studies of the sex-specificity of sexual arousal in adults (i.e., the tendency to
      respond more strongly to preferred-sex individuals than non-preferred sex
      individuals) have suggested that heterosexual men, homosexual men, and homosexual
      women show stronger sex-specific responses than do heterosexual women. Evidence
      for a similar pattern of results in studies investigating the reward value of
      faces is equivocal. Consequently, we investigated the effects of (1) sexual
      orientation (homosexual vs. heterosexual), (2) sex (male vs. female), (3) image
      sex (preferred-sex vs. non-preferred-sex), and (4) the physical attractiveness of
      the individual shown in the image on the reward value of faces. Participants were
      130 heterosexual men, 130 homosexual men, 130 heterosexual women, and 130
      homosexual women. The reward value of faces was assessed using a standard key
      press task. Multilevel modeling of responses indicated that images of preferred
      sex individuals were more rewarding than images of non-preferred-sex individuals
      and that this preferred-sex bias was particularly pronounced when more physically
      attractive faces were presented. These effects were not qualified by interactions
      involving either the sexual orientation or the sex of our participants, however,
      suggesting that the preferred-sex bias in the reward value of faces is similar in
      heterosexual men, homosexual men, heterosexual women, and homosexual women. 

PMID- 25868403
TI  - Depression and Sexual Orientation During Young Adulthood: Diversity Among Sexual
      Minority Subgroups and the Role of Gender Nonconformity.
AB  - Sexual minority individuals are at an elevated risk for depression compared to
      their heterosexual counterparts, yet less is known about how depression status
      varies across sexual minority subgroups (i.e., mostly heterosexuals, bisexuals,
      and lesbians and gay men). Moreover, studies on the role of young adult gender
      nonconformity in the relation between sexual orientation and depression are
      scarce and have yielded mixed findings. The current study examined the
      disparities between sexual minorities and heterosexuals during young adulthood in
      concurrent depression near the beginning of young adulthood and prospective
      depression 6 years later, paying attention to the diversity within sexual
      minority subgroups and the role of gender nonconformity. Drawn from the National
      Longitudinal Study of Adolescent Health (N = 9421), we found that after
      accounting for demographics, sampling weight, and sampling design, self
      identified mostly heterosexual and bisexual young adults, but not lesbians and
      gay men, reported significantly higher concurrent depression compared to
      heterosexuals; moreover, only mostly heterosexual young adults were more
      depressed than heterosexuals 6 years later. Furthermore, while young adult gender
      nonconforming behavior was associated with more concurrent depression regardless
      of sexual orientation, its negative impact on mental health decreased over time.
      Surprisingly, previous gender nonconformity predicted decreased prospective
      depression among lesbians and gay men whereas, among heterosexual individuals,
      increased gender nonconformity was not associated with prospective depression.
      Together, the results suggested the importance of investigating diversity and the
      influence of young adult gender nonconformity in future research on the mental
      health of sexual minorities.

PMID- 25868404
TI  - Optimised isolation of polysaccharides from Lentinula edodes strain NCBI JX915793
      using response surface methodology and their antibacterial activities.
AB  - Mycelial growth in a defined medium by submerged fermentation is a rapid and
      alternative method for obtaining fungal biomass of consistent quality. Biomass,
      exopolysaccharides (EPS) and intracellular polysaccharides (IPS) production were
      optimised by response surface methodology in Lentinula edodes strain LeS (NCBI
      JX915793). The optimised conditions were pH 5.0, temperature 26 degrees C,
      incubation period of 25 days and agitation rate of 52 r/min for L. edodes strain
      LeS. Under the calculated optimal culture conditions, biomass production (5.88 mg
      mL(-1)), EPS production (0.40 mg mL(-1)) and IPS production (12.45 mg g(-1)) were
      in agreement with the predicted values for biomass (5.93 mg mL(-1)), EPS (0.55 mg
      mL(-1)) and IPS production (12.64 mg g(-1)). Crude lentinan exhibited highest
      antibacterial effects followed by alcoholic, crude and aqueous extracts. The
      results obtained may be useful for highly effective yield of biomass and
      bioactive metabolites.

PMID- 25868405
TI  - Serious congenital heart disease and necrotizing enterocolitis in very low birth
      weight neonates.
AB  - BACKGROUND: Infants with serious congenital heart disease (CHD) appear to be at
      increased risk for necrotizing enterocolitis (NEC). This study aimed to quantify
      the incidence and mortality of NEC among very low birth weight (VLBW) neonates
      with serious CHD, and identify specific CHD diagnoses at the highest risk for
      developing NEC. STUDY DESIGN: Data were prospectively collected on 257,794 VLBW
      (401 to 1,500 g) neonates born from 2006 to 2011 and admitted to 674 Vermont
      Oxford Network US centers. Entries were coded for specific CHD diagnoses and
      reviewed for completeness and consistency. Survival was defined as alive in
      hospital at 1 year or discharge. RESULTS: Of eligible neonates, 1,931 had serious
      CHD. Of these, 253 (13%) developed NEC (vs 9% in infants without CHD, adjusted
      odds ratio [AOR] 1.80, p<0.0001). Mortality for neonates with CHD and no NEC was
      34%, vs 55% for those with CHD and NEC (p<0.0001). Both groups of CHD patients
      had higher mortality than infants with NEC without CHD (28%, p<0.0001). Although
      NEC mortality overall decreases with higher birth weight, mortality for NEC and
      CHD together does not. CONCLUSIONS: The incidence of NEC is significantly higher
      in VLBW neonates when CHD is present. The mortality of CHD and NEC together is
      substantially higher than that with each disease alone. Infants with
      atrioventricular canal appear to have higher risk for developing NEC than other
      CHD diagnoses. In addition to providing benchmark incidence and mortality data,
      these findings may have utility in the further study of the pathophysiology of
      NEC.

PMID- 25868406
TI  - Repair of Paraesophageal Hiatal Hernias-Is a Fundoplication Needed? A Randomized
      Controlled Pilot Trial.
AB  - BACKGROUND: The need for a fundoplication during repair of paraesophageal hiatal
      hernias (PEH) remains unclear. Prevention of gastroesophageal reflux represents a
      trade-off against the risk of fundoplication-related side effects. The aim of
      this trial was to compare laparoscopic mesh-augmented hiatoplasty with simple
      cardiophrenicopexy (LMAH-C) with laparoscopic mesh-augmented hiatoplasty with
      fundoplication (LMAH-F) in patients with PEH. STUDY DESIGN: The study was
      designed as a patient- and assessor-blinded randomized controlled pilot trial,
      registration number: DRKS00004492 (www.germanctr.de/). Patients with symptomatic
      PEH were eligible and assigned by central randomization to LMAH-C or LMAH-F.
      Endpoints were postoperative gastroesophageal reflux, complications, and quality
      of life 12 months postoperatively. RESULTS: Forty patients (9 male, 31 female)
      were randomized. Patients were well matched for baseline characteristics. At 3
      months, the DeMeester score was higher after LMAH-C compared with LMAH-F (40.9 +/
      39.9 vs. 9.6 +/- 17; p = 0.048). At 12 months, the reflux syndrome score was
      higher after LMAH-C compared with LMAH-F (1.9 +/- 1.2 vs. 1.1 +/- 0.4; p =
      0.020). In 53% of LMAH-C patients and 17% of LMAH-F patients, postoperative
      esophagitis was present (p = 0.026). Values of dysphagia (2.1 +/- 1.6 vs 1.9 +/-
      1.4; p = 0.737), gas bloating (2.6 +/- 1.4 vs 2.8 +/- 1.4; p = 0.782), and
      quality of life (116.0 +/- 16.2 vs 115.9 +/- 15.8; p = 0.992) were similar.
      Relevant postoperative complications occurred in 4 (10%) patients and did not
      differ between the groups. CONCLUSIONS: Laparoscopic repair of PEH should be
      combined with a fundoplication to avoid postoperative gastroesophageal reflux and
      resulting esophagitis. Fundoplication-related side effects do not appear to be
      clinically relevant. Multicenter randomized trials are required to confirm these
      findings.

PMID- 25868407
TI  - Lobectomy by Video-Assisted Thoracic Surgery vs Muscle-Sparing Thoracotomy for
      Stage I Lung Cancer: A Critical Evaluation of Short- and Long-Term Outcomes.
AB  - BACKGROUND: Propensity-matched studies have shown lobectomy by VATS to be
      superior to thoracotomy. However, these studies do not control for institution or
      surgeon expertise and do not compare VATS strictly with muscle-sparing
      thoracotomy (MST). STUDY DESIGN: From a single surgeon experienced in both VATS
      and MST, patients undergoing lobectomy for clinical stage I non-small cell cancer
      were evaluated. Video-assisted thoracic surgery was chosen if the patient
      requested this approach, otherwise MST was used. Short-term and long-term
      outcomes were compared. RESULTS: From 2007 to 2012, two hundred and ninety-eight
      patients were evaluated, 74 (25%) VATS and 224 (75%) MST. There were no
      statistically significant differences in demographics, chest tube days, and
      postoperative complications between the 2 surgical groups. Operative time was
      longer for VATS (median 130 minutes for VATS vs 90 minutes for MST; p<0.001).
      Hospital length of stay was longer for MST (median 4.5 days for VATS vs 5 days
      for MST; p=0.007). There was no difference in disease-free survival (5-year: 76%
      for VATS vs 78% for MST; p=0.446) and overall survival (5-year: 80% for VATS vs
      79% for MST; p=0.840) for clinical stage I disease. Results were unchanged using
      propensity score matching of 60 VATS and 60 MST patients for postoperative
      complications, disease-free survival, and overall survival between the 2 matched
      groups. CONCLUSIONS: Our current comparison of VATS vs MST, from a single surgeon
      experienced with both approaches, found operative time (favoring MST) and
      hospital days (favoring VATS) to be the only difference between the 2 groups; and
      major outcomes, such as postoperative complications, disease-free survival, and
      overall survival, were not different. A multi-institution randomized trial should
      be considered before deeming any one approach to be superior.

PMID- 25868408
TI  - The race to liver transplantation: a comparison of patients with and without
      hepatocellular carcinoma from listing to post-transplantation.
AB  - BACKGROUND: There are geographic and disease-specific inequities in liver
      allograft distribution. We examined differences between hepatocellular carcinoma
      (HCC) and non-HCC liver transplantation (LT) candidates from listing through LT
      in a region with prolonged wait times. STUDY DESIGN: We performed a single-center
      retrospective study, from 2005 to 2013, of adult, primary, nonstatus 1 candidates
      who were listed and subsequently underwent LT (n=270), or were removed because of
      death or clinical deterioration (n=277). RESULTS: Of the HCC candidates removed
      from the waitlist (n=184), 5.5% died waiting, 25.5% deteriorated clinically, and
      69% had LT. Of the non-HCC candidates (n=363), 38.8% died waiting, 21.8%
      clinically deteriorated, and 39.4% had LT. Of the LT recipients, 127 (47%) had
      HCC. When compared with non-HCC transplant recipients, HCC recipients spent more
      time on the waitlist (435+/-475 vs 301+/-604 days, p=0.045) and from listing
      until LT had higher total pre-transplant hospital admissions per patient (1.1+/
      1.2 vs 0.8+/-1.8, p<0.001). These admissions were more often planned (0.65+/-0.88
      vs 0.17+/-0.52 planned admissions per patient, p<0.001) and of shorter duration
      (2.7+/-2.8 vs 5.2+/-4.6 days, p<0.001). The HCC and non-HCC recipients
      demonstrated similar overall post-transplant survival (5 year 80% vs. 83%,
      respectively; p=0.84). CONCLUSIONS: Despite a shorter wait to have LT, non-HCC
      candidates at our center have inferior waitlist outcomes. National
      reprioritization of liver allocation to improve access for non-HCC candidates may
      lead to increased wait time and resource use for the HCC population; however, a
      mortality benefit may exist for the non-HCC candidate lacking the benefit of
      time.

PMID- 25868409
TI  - Prospective Randomized Controlled Trial Comparing the Effects of Noncontact Low
      Frequency Ultrasound with Standard Care in Healing Split-Thickness Donor Sites.
AB  - BACKGROUND: Skin graft donor sites are notoriously painful, with potential
      complications of fluid loss, delayed healing, infection, and hypertrophic
      scarring, particularly in patients with burns or traumatic injury. In this
      population, rapid epithelialization is critical to reducing morbidity and cost.
      STUDY DESIGN: This prospective, randomized controlled trial compared the effects
      of 40-kHz noncontact low-frequency ultrasound (NLFU) in addition to standard care
      (SC) with SC alone in subjects with split-thickness donor sites of 20 to 200
      cm(2). Standard care consisted of cleansing and moist wound dressings. Outcomes
      measured were time to healing, defined as absence of drainage and full
      epithelialization; pain and itching scores; and recidivism rates. RESULTS: Of 33
      patients enrolled; 27 were randomized and received a minimum of 4 study
      treatments. Median age was 49 years, 69% were male, and 84% were burn patients.
      Comorbidities included hypertension (31%), coronary artery disease (22%),
      pulmonary disease (38%), anemia (31%), and diabetes (16%). Median donor site area
      was 136.0 cm(2). Noncontact low-frequency ultrasound and SC compared with SC
      demonstrated a mean time to heal of 12.1 days vs 21.3 days (p = 0.04). All
      NLFU+SC subjects had epithelialized by 4 weeks compared with only 71% in SC.
      Recidivism rates were 8% for NLFU+SC compared with 45% for SC. Pain scores were
      reduced and significant differences in itching were observed. CONCLUSIONS:
      Noncontact low-frequency ultrasound and SC compared with SC alone in the
      treatment of split-thickness donor sites demonstrated significant accelerated
      healing and reduced pain and itching. Noncontact low-frequency ultrasound
      subjects experienced a better quality of healing with less incidence of infection
      and recidivism.

PMID- 25868410
TI  - Neoadjuvant chemotherapy for breast cancer increases the rate of breast
      conservation: results from the National Cancer Database.
AB  - BACKGROUND: Neoadjuvant chemotherapy has been shown to increase the rate of
      breast conservation in clinical trials and small institutional series, but it has
      never been studied on a national level. STUDY DESIGN: We performed a
      retrospective review of the National Cancer Database (NCDB). The NCDB is a joint
      project of the Commission on Cancer of the American College of Surgeons and the
      American Cancer Society and contains about 80% of the cancer cases in the United
      States. All women in the NCDB diagnosed with invasive breast cancer from 2006
      through 2011, who underwent definitive breast surgery and received either
      neoadjuvant or adjuvant chemotherapy, excluding patients with distant metastases
      or T4 tumors, were included and rates of breast preservation were determined.
      RESULTS: Of 354,204 patients who met the inclusion criteria, 59,063 (16.7%)
      underwent neoadjuvant chemotherapy. This proportion steadily increased from 13.9%
      in 2006 to 20.5% in 2011 (p<0.001). Receipt of neoadjuvant chemotherapy was
      associated with larger tumor size (7% cT1, 25% cT2, and 58% cT3; p<0.001), more
      advanced nodal disease (11% cN0, 39% cN1-3; p<0.001), younger patient age (21%<50
      years vs 14%>50 years; p<0.001), higher tumor grade (18% grade 3, 15% grade 2, vs
      12% grade 1; p<0.001), and estrogen receptor (ER)-negative tumors (21% ER
      negative vs 15% ER postive; p<0.001). Multivariate logistic regression showed
      that when adjusted for the above variables, patients with tumors larger than 3 cm
      undergoing neoadjuvant chemotherapy were more likely to receive breast
      preservation than those who opted for primary surgery (odds ratio 1.7, 95% CI 1.6
      to 1.8). CONCLUSIONS: Neoadjuvant chemotherapy increases breast preservation for
      patients with breast tumor size larger than 3 cm.

PMID- 25868411
TI  - Educating surgeons may allow for reduced intraoperative costs for inguinal
      herniorrhaphy.
AB  - BACKGROUND: Our aim was to determine the impact of surgeon education regarding
      disposable supply costs to reduce intraoperative costs for a common procedure
      such as inguinal hernia repair. STUDY DESIGN: At the end of the 2013 fiscal year
      (FY 13), surgeons in our department were provided with information about the cost
      of disposable equipment and implants used in common general surgery operations.
      Surgeons who historically had lower supply costs demonstrated individual
      techniques to their colleagues. No financial incentive or punitive measures were
      used to encourage behavior change. Surgical supply costs for laparoscopic and
      open inguinal hernia repair in FY13 were then compared with costs during fiscal
      year 2014 (FY14) using Mann-Whitney U tests. RESULTS: The average cost of
      laparoscopic inguinal hernia repairs decreased from an average $1,088+/-473 (+/
      SD) in FY13 (n=258) to $860+/-441 (n=274) in FY14 after surgeon education,
      representing a 21.0% reduction in intraoperative costs (p<0.001). The most
      impactful adjustments to reduce costs included selective use of mesh fixation
      devices (22.9%) and balloon dissecting trocars (27.6%), reduction in use of
      disposable scissors (13.8%), and reduction in use of disposable clip appliers
      (3.7%). Open inguinal hernia costs were reduced from an average (+/-SD) of $315+/
      $253 in FY13 (n=366) to $288+/-$130 in FY14 (n=286), an 8.6% reduction in cost
      (p<0.01). In these cases, both avoiding the use of fixation devices and using
      less expensive mesh implants were identified as significant factors. CONCLUSIONS:
      Surgeon education and empowerment may significantly reduce the cost of disposable
      equipment in laparoscopic and open inguinal hernia repair. This simple
      educational technique could prove financially beneficial throughout various
      procedures and disciplines.

PMID- 25868412
TI  - Real-Time Super Selective Venous Sampling in Remedial Parathyroid Surgery.
AB  - BACKGROUND: Remedial cervical exploration for persistent or recurrent primary
      hyperparathyroidism can be technically difficult, but is expedited by accurate
      preoperative localization. We investigated the use of real-time super selective
      venous sampling (sSVS) in the setting of negative noninvasive imaging modalities.
      STUDY DESIGN: We performed a retrospective analysis of a prospective database
      incorporating real-time sSVS in a tertiary academic medical center. Between
      September 2001 and April 2014, 3,643 patients were referred for surgical
      treatment of primary hyperparathyroidism. Of these, 31 represented remedial
      patients who had undergone one (n=28) or more (n=3) earlier cervical explorations
      and had noninformative, noninvasive preoperative localization studies. RESULTS:
      We extended the use of the rapid parathyroid hormone assay in the interventional
      radiology suite, generating near real-time data facilitating onsite venous
      localization by a dedicated interventional radiologist. The predictive value of
      real-time sSVS localization was investigated. Overall, sSVS correctly predicted
      the localization of the affected gland in 89% of cases. Of 31 patients who
      underwent sSVS, a significant rapid parathyroid hormone gradient was identified
      in 28 (90%), localizing specific venous drainage of a culprit gland. All patients
      underwent subsequent surgery and were biochemically cured, with the exception of
      one who had metastatic parathyroid carcinoma. Three patients with negative sSVS
      were also explored and cured. CONCLUSIONS: Preoperative parathyroid localization
      is of paramount importance in remedial cervical explorations. Real-time sSVS is a
      sensitive localization technique for patients with persistent or recurrent
      primary hyperparathyroidism, when traditional noninvasive imaging studies fail.
      These results validate the utility and benefit of real-time sSVS in guiding
      remedial parathyroid surgery.

PMID- 25868413
TI  - Multidisciplinary teamwork improves use of the operating room: a multicenter
      study.
AB  - BACKGROUND: Poor inter-professional collaboration might negatively influence
      adequate planning of operative procedures. Interventions capable of improving
      inter-professional collaboration will positively impact professional practice and
      health care outcomes. Radboud University Medical Center (UMC) redesigned their
      operating room (OR) scheduling method by implementing cross-functional teams
      (CFTs). In this center, positive effects of CFTs were already demonstrated in a
      mono-center study. This study aims to confirm these effects by comparing the
      Radboud data with data from 6 other similar centers using a nationwide OR
      benchmark collaborative. STUDY DESIGN: The effect of CFTs was measured by the
      performance indicator "raw utilization." The Kruskal-Wallis one-way ANOVA was
      applied to compare OR performance among all 7 centers. The Wilcoxon-Mann-Whitney
      test was used to determine differences in OR performance between Radboud UMC and
      the control group. RESULTS: Operating room performance differed significantly
      among all 7 centers (p<0.0005). Radboud UMC demonstrated the highest median raw
      utilization of 94% vs 85% in the control group (p<0.0005). Box-and-whisker plots
      validated the reduced variation during the years, indicating an organizational
      learning effect. Therefore, not only a better performance than the control group,
      but also a gradual improvement of this performance during the years. CONCLUSIONS:
      This study shows that multidisciplinary collaboration in CFTs during the
      perioperative phase has a positive influence on OR scheduling and use of OR time.
      Other national databases considering mortality rates also support the idea that
      introducing CFTs is not only an important condition for improving OR performance,
      but also for improving quality of care.

PMID- 25868414
TI  - Vertical rectus muscle flap repair for perineal defect: abdominoperineal
      resection and perineal hernia.

PMID- 25868415
TI  - Analysis of cyst size and tumor markers in the management of pancreatic cysts:
      support for the original Sendai criteria.
AB  - BACKGROUND: In 2006, the Sendai Consensus Guidelines identified size >3.0 cm as
      the only independent predictor of malignancy in incidentally discovered
      pancreatic cysts. The 2012 updated guidelines increased emphasis on radiographic
      features over size. Earlier studies included patients with preoperatively
      diagnosed carcinoma or with a corresponding mass. In this report, we characterize
      the use of size and serum tumor markers in the initial evaluation of pancreatic
      cystic neoplasms without preoperatively diagnosed adenocarcinoma and correlate
      them with clinical and pathologic outcomes. STUDY DESIGN: A retrospective cohort
      study was undertaken of 112 patients with a resected pancreatic cystic neoplasm.
      Patient demographics, cyst characteristics, preoperative serum tumor markers,
      morbidity, and mortality were captured. Statistical analysis included
      nonparametric tests of comparison, multivariate logistic regression, and receiver
      operating characteristic curve analyses. RESULTS: One hundred and twelve
      pancreatic cystic neoplasms were resected; there was one perioperative death.
      Mucinous cysts were common (78%), followed by serous cysts (13%). In total, 17%
      of cysts harbored malignancy. On multivariate analysis, the risk of malignancy in
      cysts>=3 cm was more than 4 times that of smaller cysts (relative risk (RR)=4.32;
      95% CI, 1.55-12.07). There was no significant difference in serum CEA, cancer
      antigen 19-9, or cyst-fluid CEA levels between the benign and malignant groups.
      At a median follow-up of 30 months, the incidence of diabetes was 15%.
      CONCLUSIONS: Surgical resection of pancreatic cysts can be performed with low
      perioperative mortality and acceptable long-term morbidity. Use of cyst size as a
      rationale for resection of cystic lesion, as per the Sendai criteria, is
      justified.

PMID- 25868416
TI  - Modeling Evacuation of a Hospital without Electric Power.
AB  - Hospital evacuations that occur during, or as a result of, infrastructure outages
      are complicated and demanding. Loss of infrastructure services can initiate a
      chain of events with corresponding management challenges. This report describes a
      modeling case study of the 2001 evacuation of the Memorial Hermann Hospital in
      Houston, Texas (USA). The study uses a model designed to track such cascading
      events following loss of infrastructure services and to identify the staff,
      resources, and operational adaptations required to sustain patient care and/or
      conduct an evacuation. The model is based on the assumption that a hospital's
      primary mission is to provide necessary medical care to all of its patients, even
      when critical infrastructure services to the hospital and surrounding areas are
      disrupted. Model logic evaluates the hospital's ability to provide an adequate
      level of care for all of its patients throughout a period of disruption. If
      hospital resources are insufficient to provide such care, the model recommends an
      evacuation. Model features also provide information to support evacuation and
      resource allocation decisions for optimizing care over the entire population of
      patients. This report documents the application of the model to a scenario
      designed to resemble the 2001 evacuation of the Memorial Hermann Hospital,
      demonstrating the model's ability to recreate the timeline of an actual
      evacuation. The model is also applied to scenarios demonstrating how its output
      can inform evacuation planning activities and timing.

PMID- 25868417
TI  - Seroprevalence of lyme borreliosis in Scottish blood donors.

PMID- 25868418
TI  - [Not Available].

PMID- 25868419
TI  - [Not Available].

PMID- 25868420
TI  - [Migration and infectious disease surveillance in Germany: Analyses of
      Tuberculosis, HIV and Syphilis surveillance data].
AB  - BACKGROUND: Migration is an important factor impacting on infectious disease
      epidemiology. The timely identification of groups at risk and prevention needs
      resulting from migration is indispensable to adequately design and implement
      public health measures. It remains to be assessed to which extent surveillance
      data for notifiable diseases can directly generate meaningful migration-specific
      information. OBJECTIVES: The objectives of this study are to review indicators of
      migration background utilized in the German infectious disease surveillance, as
      well as to assess their limitations. METHODS: We describe the indicators of
      migration used for mandatorily notifiable diseases and pathogens and their legal
      basis in the Protection against Infection Act and conduct a descriptive analysis
      of surveillance data for tuberculosis (TB), HIV and syphilis from 2002-2013.
      RESULTS: Migration status is collected only for five infectious diseases and
      operationalization varies. For TB (country of birth) and HIV (country of origin)
      a foreign origin was more frequent than for syphilis (country of origin); namely
      46, 30 and 13% of cases with available information, respectively. In all three
      examples, there are indications of risk profiles that are specific for particular
      groups of migrants. DISCUSSION: A standardization of indicators of migration in
      infectious disease surveillance is important to enhance data comparability
      between diseases and pathogens as well as across countries. Routine surveillance
      already partly allows migration sensitive analyses, yet further research is
      needed to guide interpretation of the complex relationship between migration and
      infectious diseases and plan public health measures adequately.

PMID- 25868421
TI  - Perfluorooctanoic acid (PFOA) affects distinct molecular signalling pathways in
      human primary hepatocytes.
AB  - Perfluorooctanoic acid (PFOA) was shown to damage the liver of rodents and to
      impair embryonic development. At the molecular level, the hepatotoxic effects
      were attributed to the PFOA-mediated activation of peroxisome proliferator
      activated receptor alpha (PPARalpha). In general, PPARalpha-dependent effects are
      less pronounced in humans than in rodents, and the hazard potential of PFOA for
      humans is controversially discussed. To analyse the effects of PFOA in human
      hepatocytes, a microarray analysis was conducted to screen for PFOA-mediated
      alterations in the transcriptome of human primary hepatocytes. A subsequent
      network analysis revealed that PFOA had an impact on several signalling pathways
      in addition to the well-known activation of PPARalpha. The microarray data
      confirmed earlier findings that PFOA: (i) affects the estrogen receptor ERalpha,
      (ii) activates the peroxisome proliferator-activated receptor gamma (PPARgamma),
      and (iii) inhibits the function of the hepatocyte nuclear factor 4alpha
      (HNF4alpha) which is an essential factor for liver development and embryogenesis.
      Finally, as a novel finding, PFOA was shown to stimulate gene expression of the
      proto-oncogenes c-Jun and c-Fos. This was confirmed by using the HepG2 cell line
      as a model for human hepatocytes. PFOA stimulated cellular proliferation and the
      metabolic activity of the cells, and upregulated the expression of various
      cyclins which have a central function in the regulation of cell cycle control.
      Functional studies, however, indicated that PFOA had no impact on c-Jun and c-Fos
      phosphorylation and on AP-1-dependent gene transcription, thus demonstrating that
      PFOA-induced proliferation occurs largely independent of c-Jun and c-Fos. 

PMID- 25868422
TI  - Bariatric surgery associated with percutaneous auricular vagal stimulation: A new
      prospective treatment on weight loss.

PMID- 25868423
TI  - Impact of duration of diabetes on outcome following pancreas transplantation.
AB  - INTRODUCTION: The impact of duration of T1DM on outcomes following simultaneous
      pancreas and kidney transplantation (SPK), pancreas after kidney transplantation
      (PAK), and pancreas transplantation alone (PTA) is currently unknown. MATERIALS
      AND METHODS: A total of 451 pancreas transplants performed at a single
      institution between January 2003 and April 2013 (SPK n = 238, PAK, n = 97, and
      PTA, n = 116) were divided into three groups based on cumulative years of T1DM (0
      20 years, 21-30 years, and >30 years). Early (7-day) and late (90-day) pancreas
      allograft loss, patient and pancreas allograft survivals were analyzed. RESULTS:
      While, PAK was more common in recipients with >30 years of T1DM (29%, p <
      0.0047), PTA was more common in recipients with 0-20 years of T1DM (41%, p <
      0.0011). In all transplant types, recipients age was significantly higher the
      longer the duration of diabetes. Although longer duration of T1DM correlated with
      a higher rate of major amputations in PAK recipients (p < 0.0032), no difference
      was observed in SPK or PTA. While early pancreas graft loss was 2-4% in SPK and
      PAK with shorter or longer T1DM (p = n.s.), it reached to 10% in PTA with T1DM >
      30 years (p < 0.0097). Longer duration of T1DM affected late pancreas graft loss
      in PAK patients (8%, p < 0.0349). Patient and death-censored graft survival rates
      were similar in all types of pancreas transplantation extracted by accumulation
      of years of T1DM prior to transplant. CONCLUSIONS: Longstanding T1DM does not
      seem to negatively impact recipient outcomes following all types of pancreas
      transplantation.

PMID- 25868425
TI  - A straightforward implementation of in situ solution electrochemical 13C NMR
      spectroscopy for studying reactions on commercial electrocatalysts: ethanol
      oxidation.
AB  - Identifying and quantifying electrocatalytic-reaction-generated solution species,
      be they reaction intermediates or products, are highly desirable in terms of
      understanding the associated reaction mechanisms. We report herein a
      straightforward implementation of in situ solution electrochemical (13)C NMR
      spectroscopy for the first time that enables in situ studies of reactions on
      commercial fuel-cell electrocatalysts (Pt and PtRu blacks). Using ethanol
      oxidation reaction (EOR) as a working example, we discovered that (1) the
      complete oxidation of ethanol to CO2 only took place dominantly at the very
      beginning of a potentiostatic chronoamperometric (CA) measurement and (2) the
      PtRu had a much higher activity in catalysing oxygen insertion reaction that
      leads to acetic acid. 

PMID- 25868424
TI  - A wearable mobility assessment device for total knee replacement: A longitudinal
      feasibility study.
AB  - BACKGROUND: Total knee replacement currently lacks robust indications and
      objective follow-up metrics. Patients and healthcare staff are under-equipped to
      optimise outcomes. This study aims to investigate the feasibility of using an ear
      worn motion sensor (e-AR, Imperial College London) to conduct objective, home
      based mobility assessments in the peri-operative setting. METHODS: Fourteen
      patients on the waiting list for knee replacement, and 15 healthy subjects, were
      recruited. Pre-operatively, and at 1, 3, 6, 12 and 24 weeks post-operatively,
      patients underwent functional mobility testing (Timed Up and Go), knee
      examination (including range of motion), and an activity protocol whilst wearing
      the e-AR sensor. Features extracted from sensor motion data were used to assess
      patient performance and predict patients' recovery phase. RESULTS: Sensor-derived
      peri-operative mobility trends correlated with clinical measures in several
      activities, allowing functional recovery of individual subjects to be profiled
      and compared, including the detection of a complication. Sensor data features
      enabled classification of subjects into normal, pre-operative and 24-week post
      operative groups with 89% (median) accuracy. Classification accuracy was reduced
      to 69% when including all time intervals. DISCUSSION: This study demonstrates a
      novel, objective method of assessing peri-operative mobility, which could be used
      to supplement surgical decision-making and facilitate community-based follow-up.

PMID- 25868426
TI  - Gender, educational and ethnic differences in active life expectancy among older
      Singaporeans.
AB  - AIM: The aim of the present study was to compute total life expectancy (TLE),
      active life expectancy (ALE) and inactive life expectancy among older
      Singaporeans by gender, education and ethnicity. METHODS: Data from a
      longitudinal survey of older Singaporeans were used. No difficulty in carrying
      out activities of daily living or instrumental activities of daily living was
      considered as "active." Transition probabilities across health states
      (active/inactive/dead) were assessed to develop multistate life tables, which
      estimated TLE, ALE and inactive life expectancy. RESULTS: At age 60 years, women,
      versus men, had significantly higher TLE (25.9, 95% confidence interval [CI] 24.0
      27.8 vs 21.6, 95% CI 20.1-23.1), but similar ALE (18.1, 95% CI 17.0-19.2 vs 18.9,
      95% CI 17.7-20.2). Those with high (secondary or higher), versus low (primary or
      less), education had significantly higher TLE (28.5, 95% CI 25.0-32.0 vs 22.5,
      95% CI 21.1-23.9) and ALE (23.5, 95% CI 21.2-25.7 vs 17.1, 95% CI 16.1-18.0) at
      age 60 years. Those of Chinese, versus non-Chinese, ethnicity had significantly
      higher ALE at age 60 years (19.4, 95% CI 18.4-20.3 vs 15.0, 95% CI 13.4-16.7).
      CONCLUSION: Unlike Western nations, there was no gender difference in ALE among
      older adults in Singapore. However, difference in ALE by education among older
      Singaporeans was similar to that observed in Western societies. Policies focusing
      specifically on improving women's health at all ages, in addition to policies
      that increase population education levels, are promising approaches to improving
      ALE. Recognizing ethnic differences in ALE will help target policies that
      increase ALE in multicultural societies.

PMID- 25868427
TI  - Acute abdominal pain as the only symptom of a thoracic demyelinating lesion in
      multiple sclerosis.
AB  - Multiple sclerosis (MS) is a syndrome characterized by complex neurological
      symptoms resulting from demyelinating lesions in the central nervous system. We
      report a child with a relapse of MS whose only presenting symptom was severe
      abdominal pain. Dysfunctional intestinal mobility was assessed by abdominal
      computed tomography. Findings resembled paralytic ileus resulting from
      peritonitis. However, the patient demonstrated no other symptoms of peritonitis.
      A T2-weighted magnetic resonance image revealed a new demyelinating lesion
      localized to thoracic segments T4-T12. The lesion presumably affected autonomic
      efferents involved in intestinal mobility. Treatment with a pulse of
      methylprednisolone reduced both abdominal pain and lesion size. To our knowledge,
      this is the first reported case of a pediatric MS patient with a demyelinating
      lesion associated with an autonomic symptom of altered intestinal mobility in the
      absence of neurological symptoms. This atypical presentation of MS highlights the
      need for physicians' vigilance when treating this patient population. 

PMID- 25868428
TI  - The mortality of neonatal herpes simplex virus infection.
AB  - This retrospective study characterized the clinical course of 13 neonates who
      died with herpes simplex virus infection from 2001 to 2011, representing a 26%
      case-fatality rate. Fatal disease developed at <= 48 hours of age in one-third of
      infants, was mostly disseminated disease, and occurred despite early
      administration of high-dose acyclovir therapy.

PMID- 25868429
TI  - Safety of the One-Step Percutaneous Endoscopic Gastrostomy Button in Children.
AB  - Pediatric experience using the single-stage percutaneous endoscopic gastrostomy
      button has been reported anecdotally. This 3-year prospective monocentric study,
      including 183 children, demonstrates that this technique is safe, with a low rate
      of infection, and compares favorably with the pull technique of percutaneous
      endoscopic gastrostomy while necessitating only one general anesthesia. 

PMID- 25868430
TI  - Riga-Fede Disease: Traumatic Lingual Ulceration in an Infant.

PMID- 25868432
TI  - Risk factors for complications in infants and children with percutaneous
      endoscopic gastrostomy tubes.
AB  - OBJECTIVE: To identify risk factors associated with percutaneous endoscopic
      gastrostomy (PEG) tube complications in a large cohort of infants and children.
      STUDY DESIGN: We performed a chart review of 591 pediatric patients undergoing
      PEG tube placement between 2006 and 2010 at Boston Children's Hospital. Frequency
      and type of major and minor complications associated with PEG tubes in children
      were identified. Univariate and multivariate analyses were then conducted to
      determine potential risk factors for complications. RESULTS: A total of 198 PEG
      related complications (72 major and 126 minor) were noted in our cohort of 591
      patients. Approximately 10.5% of patients experienced at least one major
      complication and 16.4% experienced at least one minor complication, with the
      great majority of complications occurring after discharge postplacement. Age <6
      months (P = .003), American Society of Anesthesiologists class III (P = .02), and
      presence of a neurologic disorder (P = .05) were found to be protective against
      experiencing a major complication, whereas the presence of a ventriculoperitoneal
      shunt was confirmed to be a risk factor (P = .01) for major complications.
      CONCLUSION: Both minor and major complications are common in children after PEG
      tube placement, with most complications occurring several months postoperatively.
      Certain patient factors, including age, neurologic status, and American Society
      of Anesthesiologists class, may be protective, and the presence of a
      ventriculoperitoneal shunt may be associate with an increased risk of
      complications after PEG tube placement.

PMID- 25868431
TI  - Preterm Birth Is Associated with Higher Uric Acid Levels in Adolescents.
AB  - OBJECTIVE: To compare serum uric acid levels in adolescents born prematurely and
      adolescents born at term and to assess the correlation between serum uric acid
      and blood pressure (BP) in those born prematurely. STUDY DESIGN: In this
      observational cohort study, 124 adolescents born prematurely and 44 adolescents
      born at term were studied at 14 years of age. Multivariate analyses were used to
      describe the relationship of premature birth to serum uric acid while adjusting
      for confounding variables. Pearson correlation was used to describe the
      relationship between uric acid and systolic BP among those born prematurely.
      RESULTS: Adjusting for race, sex, maternal hypertension, and fetal growth, we
      found that preterm adolescents had greater serum uric acid levels than
      adolescents born at term (adjusted mean difference 0.46, 95% CI 0.10-0.81 mg/dL;
      27.4, 6-48.2 MUmol/L; P = .012). Among those born prematurely, uric acid was
      positively correlated with systolic BP (Pearson correlation coefficient: 0.29,
      0.12-0.44; P = .0013). CONCLUSIONS: Serum uric acid levels are greater in
      adolescents born prematurely than in those born at term, and this difference
      could contribute to greater BP among individuals born prematurely.

PMID- 25868433
TI  - Is Menstrual Dysphonia Associated With Greater Disability and Lower Quality of
      Life?
AB  - OBJECTIVES: The aim of the present study had been to examine the relationships
      between menstrual dysphonia and measures of psychosocial distress, in a sample of
      female professional voice users. DESIGN AND METHODS: This is a prospective study
      of 52 consecutive professional voice users, aged 18-40 years, affected by
      transient dysphonia related to the menstrual cycle and recruited in the Division
      of Phoniatrics and Audiology of the Second University of Naples, from April 2011
      to September 2014. The following evaluation protocol was used: videoendoscopy,
      the GIRBAS scale, the Voice Handicap Index, and the determination of sexual
      hormonal plasma levels both during the menstrual and the luteal phase of the
      cycle. Furthermore, we measured, in all patients, the levels of perceived
      disability and quality of life during and after the dysphonia episodes by means
      of the Manchester Short Assessment of Quality of Life and the Sheehan disability
      scale. RESULTS: Laryngoscopic evaluation revealed that only minor morphologic
      changes were present during the first days of the follicular phase, usually
      returning to normal morphology after the menstrual period was over. However, we
      found that dysphonia episodes of varying degree were present in most evaluated
      subjects; women with a moderate degree of dysphonia also had a lower quality of
      life and greater overall disability, during menses. CONCLUSIONS: Despite minimal
      morphologic signs of laryngeal pathology, menstrual dysphonia might represent a
      disease which is frequent among female professional voice users, which in turn is
      associated with a certain degree of disability and lower quality of life during
      premenstrual and menstrual phases.

PMID- 25868436
TI  - Osmoregulation by juvenile brown-banded bamboo sharks, Chiloscyllium punctatum,
      in hypo- and hyper-saline waters.
AB  - While there is a considerable body of work describing osmoregulation by
      elasmobranchs in brackish and saltwater, far fewer studies have investigated
      osmoregulation in hypersaline waters. We examined osmo- and ionoregulatory
      function and plasticity in juvenile brown-banded bamboo sharks, Chiloscyllium
      punctatum, exposed to three experimental salinities (25, 34 and 400/00) for two
      weeks. C. punctatum inhabits sheltered coastal areas and bays which can naturally
      become hypersaline as a consequence of evaporation of water but can also become
      hyposaline during flood events. We hypothesised that C. punctatum would
      demonstrate a phenotypically plastic osmoregulatory physiology. Plasma
      osmolality, urea, Na(+) and Cl(-) levels increased significantly with increasing
      environmental salinity. Rectal gland and branchial sodium-potassium ATPase (NKA)
      activities were unaffected by salinity. Using immunohistochemistry and Western
      Blotting we found evidence for the presence of the key ion-regulatory proteins
      vacuolar H(+)-ATPase (VHA), pendrin (Cl(-)/HCO3(-) co-transporter) and the Na(+)
      H(+) exchanger isoform 3 (NHE3) in discrete cells within the branchial epithelia.
      These results indicate that C. punctatum is a partially euryhaline elasmobranch
      able to maintain osmo- and ionoregulatory function between environmental
      salinities of 250/00 and 400/00. As suggested for other elasmobranchs, the gills
      of C. punctatum likely play a limited role in maintaining Na(+) homeostasis over
      the salinity range studied, but may play an important role in acid-base balance.

PMID- 25868435
TI  - Limb remote ischemic per-conditioning in combination with post-conditioning
      reduces brain damage and promotes neuroglobin expression in the rat brain after
      ischemic stroke.
AB  - PURPOSE: Limb remote ischemic per-conditioning or post-conditioning has been
      shown to be neuroprotective after cerebral ischemic stroke. However, the effect
      of combining remote per-conditioning with post-conditioning on
      ischemic/reperfusion injury as well as the underlying mechanisms are largely
      unexplored. METHODS: Here, adult male Sprague Dawley rats were subjected to
      middle cerebral artery occlusion (MCAO). The limb ischemic stimulus was
      immediately applied after onset of focal ischemia (per-conditioning), followed by
      repeated short episodes of remote ischemia 24 hr after reperfusion (post
      conditioning). The infarct volume, motor function, and the expression of
      neuroglobin (Ngb) were measured at different durations after reperfusion.
      RESULTS: We found that a single episode of limb remote per-conditioning afforded
      short-term protection, but combining repeated remote post-conditioning during the
      14 days after reperfusion significantly ameliorated cerebral ischemia/reperfusion
      injury. Interestingly, we also found that ischemic per- and post-conditioning
      significantly increased expression of Ngb, an oxygen-binding globin protein that
      has been demonstrated to be neuroprotective against stroke, at peri-infarct
      regions from day 1 to day 14 following ischemia/reperfusion. CONCLUSION: Our
      results suggest that the conventional per-conditioning combined with post
      conditioning may be used as a novel neuroprotective strategy against ischemia
      reperfusion injury, and Ngb seems to be one of the important players in limb
      remote ischemia-mediated neuroprotection.

PMID- 25868437
TI  - Comparative evaluation of Na(+) uptake in Cyprinodon variegatus variegatus
      (Lacepede) and Cyprinodon variegatus hubbsi (Carr) (Cyprinodontiformes,
      Teleostei): Evaluation of NHE function in high and low Na(+) freshwater.
AB  - The euryhaline pupfish, Cyprinodon variegatus variegatus (Cvv), can successfully
      osmoregulate in >=2 mM Na(+) and a freshwater population (Cyprinodon variegatus
      hubbsi; Cvh) osmoregulates at >=0.1mM Na(+). We previously demonstrated that Cvv
      relies on an apical NKCC and NHE in the gill for Na(+) uptake in high (7mM) and
      intermediate (2 mM) Na(+) concentrations, while Cvh relies only on NHE for Na(+)
      uptake. This study investigated whether differential NHE isoform use explains
      differences in Na(+) uptake kinetics between these two populations. We further
      studied whether Cvh uses a NHE-Rh metabolon or carbonic anhydrase (CA) to
      overcome thermodynamic challenges of NHE function in dilute freshwater. Transfer
      to more dilute freshwater resulted in upregulation of nhe-2 (Cvv only) and nhe-3
      (Cvv and Cvh). Relative expression of nhe-3 compared to nhe-2 was 2-fold higher
      in Cvv, but 200-fold higher in Cvh suggesting that nhe-3 expression is an
      important freshwater adaptation for Cvh. Simultaneous measurement of Na(+) and
      Tamm flux under various conditions provided no support for a NHE-Rh metabolon in
      either population. Carbonic anhydrase activity in Cvv was comparable in 7 and 2
      mM Na(+) acclimated fish. In Cvh, CA activity increased by 75% in 0.1 mM Na(+)
      acclimated fish compared to 7 mM Na(+) fish. Ethoxzolamide had variable effects,
      stimulating and reducing Na(+) uptake in Cvv acclimated to 7 and 2 mM Na(+),
      while reducing Na(+) uptake in 7 and 0.1mM Na(+) acclimated Cvh. This suggests
      that CA plays important, but different roles in regulating Na(+) uptake in Cvv
      and Cvh.

PMID- 25868439
TI  - Editorial.

PMID- 25868438
TI  - Bookmakers and a Duty of Care: Customers' Views in England.
AB  - This paper focuses on customers' views on the extent that bookmakers and
      individuals are responsible for a duty of care. 72 participants from seven
      bookmakers in one city in England were interviewed that illustrates customers
      expect bookmakers to take 'reasonable steps' to avoid exploiting all customers.
      However, the customers' views recorded in this paper illustrate a range of views
      on what a duty of care should actually comprise with differences of opinion on
      the level of bookmakers and individuals level of responsibility, dealing with
      intoxicated customers, illegal gambling, prevention of excessive and problem
      gambling and self-exclusion. 

PMID- 25868440
TI  - Research, publishing, and forensic pathology.

PMID- 25868442
TI  - Earprints in forensic investigations.
AB  - This article provides an overview of the theoretical and practical issues
      surrounding the use of earprints in forensic research. In the first section, we
      provide a limited account of the history of earprints in forensic investigations
      and their use as evidence in court. Criticism of the use of earprints for
      individualization is addressed and fundamental questions that require attention
      are summarized. In the second section, we summarize the results of various
      studies that we have performed on earprint variation. Potential causes of
      intraindividual variation in earprint appearance are, for instance, variations in
      the way the prints are lifted, variations in the time the donor spends listening,
      and variations in the force that is applied during listening. Concerning the
      latter, we have explored various factors that could influence applied force. We
      have also studied changes in the morphology of live ears during adulthood. 

PMID- 25868441
TI  - The current state of forensic age estimation of live subjects for the purpose of
      criminal prosecution.
AB  - In recent years, many countries have experienced a sharp increase in the demand
      for forensic age estimates of live persons. From a legal perspective, such age
      estimates are carried out to determine whether a suspect without valid identity
      documents has reached the age of criminal responsibility and whether general
      criminal law in force for adults applies. In many countries, the age thresholds
      of relevance to criminal prosecution lie between 14 and 21 years.In line with
      recommendations issued by the Study Group on Forensic Age Diagnostics for
      determining the age of live subjects in criminal proceedings, a forensic age
      estimate should combine the results of a physical examination, an x-ray of the
      hand, and a dental examination that records dentition status and evaluates an
      orthopantomogram. In addition, a radiological or computed tomographic examination
      of the clavicles is recommended to establish whether a person has attained 21
      years of age.This article addresses the influence of ethnicity on the examined
      developmental systems. In so doing, the authors conclude that forensic age
      estimates should pay due heed to the proband's socioeconomic status and ethnic
      origin. 

PMID- 25868443
TI  - Lemierre syndrome : Three cases of "the forgotten" disease.
AB  - Lemierre syndrome is a rare clinical entity involving oropharyngeal infection and
      anaerobic bacteremia, followed by jugular vein septic thrombophlebitis with
      embolization and metastatic abscess formation in the lungs, liver, and other
      organs. Even though it occurs less frequently than in the pre-antibiotic era, it
      is still important both as a pathologist and as a clinician to recognize the
      typical presentation because of its lethal potential. Three clinically
      undiagnosed cases with lethal outcomes are described. All three cases presented
      as unexpected death, and all were autopsied at the Institute of Forensic
      Medicine, University of Aarhus. 

PMID- 25868444
TI  - Isolation and detection of ingested DNA from the immature stages of Calliphora
      dubia (diptera: Calliphoridae) : A forensically important blowfly.
AB  - The forensic entomologist frequently bases time since death (TSD) estimation on
      fly larvae. In some cases, the food source on which these larvae have completed
      their development may be questionable, and requires verification to ensure the
      accuracy of the TSD estimation. Ingested DNA may be isolated from the alimentary
      canal of immature insects. Previous studies have confirmed the ability to extract
      ingested DNA from the alimentary tract of third instar blowfly larvae. This study
      considers the potential to detect ingested DNA from immature stages of the blue
      bodied blowfly Calliphora dubia (Macquart) that had fed on sheep liver.
      Individuals from early first instar larvae through day 3 pupae were surface
      decontaminated, followed by DNA isolation and detection by amplifying the sheep
      satellite I region. Fragments of 197 basepairs (bp) and 87 bp were successfully
      isolated and detected in all stages of immatures until 2-day-old pupae, with
      detection at this stage being unsuccessful on 3-day-old pupae. This study
      presents a suitable protocol for the isolation and detection of ingested DNA from
      immature stages of C. dubia. 

PMID- 25868445
TI  - Fatal hemorrhage from simple lacerations of the scalp.
AB  - Scalp lacerations are frequently seen in both living trauma victims and at post
      mortem examination. In clinical circles, it is well known that even "trivial"
      lacerations of blood-rich areas such as the scalp may bleed profusely and
      persistently.It is less well known, however, that hemorrhage even from simple
      scalp lacerations may be fatal. We present seven cases in which hemorrhage from
      simple scalp lacerations was considered to be the principle cause of
      death.Chronic alcohol misuse, alcoholic liver disease, and the co-existence of
      other pathologies such as ischemic heart disease were frequently contributory
      factors. 

PMID- 25868446
TI  - Postmortem fetal extrusion in a case of maternal heroin intoxication.
AB  - A 34-year-old heroin addict in the eighth month of pregnancy was found dead in
      her apartment. The head of a fetus was partly protruding from underneath the
      woman's slip. At the time of autopsy, the body was in a state of advanced
      putrefaction with greenish discoloration of almost the complete body surface
      showing pronounced marbling and, in addition, now not only the head but also the
      upper part of the chest of a dead fetus were extruding from the birth canal with
      head presentation. Autopsy showed no signs of external violence prior to death
      and, in particular, no indication of preceding manipulations in the region of the
      obstetrical canal and the uterus could be detected. The uterine cavity showed
      pronounced putrefactive alterations with the amniotic membranes being partially
      raised and bloated in a balloon-like fashion. Toxicological analyses revealed
      acute heroin intoxication of mother and child. The immature neonate showed no
      signs of live birth. Pathogenetically, the finding of not only the head but also
      the upper part of the chest of the fetus extruding from the birth canal at the
      time of autopsy (contrary to the observation made at the death scene that only
      part of the head of the fetus was protruding) is consistent with post-mortem
      fetal extrusion caused by putrefactive gas pressure against the pregnant uterus
      as reported in the earlier German forensic pathological literature. 

PMID- 25868447
TI  - A bite into the history of the autopsy : From ancient roots to modern decay.
AB  - The autopsy has had a checkered history, much of which has been surrounded by
      controversy. The roots of human dissection are found in the ancient world where
      rumors flourished that the prosectors of the day were engaged in vivisection as
      well as dissection. Bound up with the prevailing religious and political systems
      of the day, the autopsy has alternately been prohibited and encouraged, used to
      explore the nature of disease, and conceal questionable political policy. This
      review explores the history of the autopsy from its ancient roots in Egypt,
      Mesopotamia, Alexandria, and the Far East through the dark ages to medieval times
      and beyond into the renaissance. The development of the autopsy in Europe during
      the 17th to 19th centuries is discussed before briefly considering the decline of
      this diagnostic tool in the 20th century. 

PMID- 25868448
TI  - Automated DNA profile analysis.
AB  - DNA profile analysis is not a simple process. Stringent demands are placed on the
      accuracy and consistency of forensic evidence so that complex, robust, and
      reproducible guidelines are necessary to assist the analyst and ensure mistakes
      are eliminated before a final profile is reported. The guidelines used for
      forensic DNA profile interpretation are formulated by investigation and
      statistical evaluation of all aspects of the analytical procedure. All the
      resulting rules, formulas, and thresholds are perfectly suited to programming of
      "expert systems"-software programs that imitate the human expert in decision
      based processes to formulate a conclusion. Expert systems in forensic DNA
      analysis will contribute greatly to this field by increasing analytical
      throughput. The net result of this will be an increase in the human resources
      available for the research and development of improved methodologies, to ensure
      that forensic DNA profiling continues to advance at its current impressive rate. 

PMID- 25868449
TI  - National Australian workshop consensus on the definition of SIDS and initiation
      of a uniform autopsy approach to unexpected infant and early childhood death.
AB  - Following formulation of a new definition for SIDS, a workshop was convened in
      Canberra Australia, in March 2004, by SIDS and KIDS, Australia. Attendences
      included forensic and pediatric pathologists representing major institutions from
      all Australian States and Territories. The issues of the adoption of a uniform
      definition of SIDS and a standardised autopsy approach were discussed. The
      workshop recommended adoption of the San Diego definition of SIDS as the sudden
      unexpected death of an infant under one year of age, with onset of the fatal
      episode apparently occuring during sleep, that remains unexplained after a
      thorough investigation, including performance of a complete autopsy and review of
      the circumstances of death and the clinical history. In addition the workshop
      undertook to develop autopsy guidelines as national standards for the performance
      of infant autopsies. 

PMID- 25868450
TI  - Kuppuswamy Scale for Measuring Socio-economic Status : Revised Monthly Income
      Figures for 2015.

PMID- 25868451
TI  - Precision and accuracy of clinical quantification of myocardial blood flow by
      dynamic PET: A technical perspective.
AB  - A number of exciting advances in PET/CT technology and improvements in
      methodology have recently converged to enhance the feasibility of routine
      clinical quantification of myocardial blood flow and flow reserve. Recent
      promising clinical results are pointing toward an important role for myocardial
      blood flow in the care of patients. Absolute blood flow quantification can be a
      powerful clinical tool, but its utility will depend on maintaining precision and
      accuracy in the face of numerous potential sources of methodological errors. Here
      we review recent data and highlight the impact of PET instrumentation, image
      reconstruction, and quantification methods, and we emphasize (82)Rb cardiac PET
      which currently has the widest clinical application. It will be apparent that
      more data are needed, particularly in relation to newer PET technologies, as well
      as clinical standardization of PET protocols and methods. We provide
      recommendations for the methodological factors considered here. At present,
      myocardial flow reserve appears to be remarkably robust to various methodological
      errors; however, with greater attention to and more detailed understanding of
      these sources of error, the clinical benefits of stress-only blood flow
      measurement may eventually be more fully realized. 

PMID- 25868453
TI  - Raman spectroscopy in pharmaceutical product design.
AB  - Almost 100 years after the discovery of the Raman scattering phenomenon, related
      analytical techniques have emerged as important tools in biomedical sciences.
      Raman spectroscopy and microscopy are frontier, non-invasive analytical
      techniques amenable for diverse biomedical areas, ranging from molecular-based
      drug discovery, design of innovative drug delivery systems and quality control of
      finished products. This review presents concise accounts of various conventional
      and emerging Raman instrumentations including associated hyphenated tools of
      pharmaceutical interest. Moreover, relevant application cases of Raman
      spectroscopy in early and late phase pharmaceutical development, process analysis
      and micro-structural analysis of drug delivery systems are introduced. Finally,
      potential areas of future advancement and application of Raman spectroscopic
      techniques are discussed.

PMID- 25868454
TI  - Applications of Raman spectroscopy in skin research--From skin physiology and
      diagnosis up to risk assessment and dermal drug delivery.
AB  - In the field of skin research, confocal Raman microscopy is an upcoming
      analytical technique. Substantial technical progress in design and performance of
      the individual setup components like detectors and lasers as well as the
      combination with confocal microscopy enables chemically selective and non
      destructive sample analysis with high spatial resolution in three dimensions. Due
      to these advantages, the technique bears tremendous potential for diverse skin
      applications ranging from the analysis of physiological component distribution in
      skin tissue and the diagnosis of pathological states up to biopharmaceutical
      investigations such as drug penetration kinetics within the different tissue
      layers. This review provides a comprehensive introduction about the basic
      principles of Raman microscopy highlighting the advantages and considering the
      limitations of the technique for skin applications. Subsequently, an overview
      about skin research studies applying Raman spectroscopy is given comprising
      various in vitro as well as in vivo implementations. Furthermore, the future
      perspective and potential of Raman microscopy in the field of skin research are
      discussed. 

PMID- 25868452
TI  - Engineered nanoparticles mimicking cell membranes for toxin neutralization.
AB  - Protein toxins secreted from pathogenic bacteria and venomous animals rely on
      multiple mechanisms to overcome the cell membrane barrier to inflict their
      virulence effect. A promising therapeutic concept toward developing a broadly
      applicable anti-toxin platform is to administer cell membrane mimics as decoys to
      sequester these virulence factors. As such, lipid membrane-based nanoparticulates
      are an ideal candidate given their structural similarity to cellular membranes.
      This article reviews the virulence mechanisms employed by toxins at the cell
      membrane interface and highlights the application of cell-membrane mimicking
      nanoparticles as toxin decoys for systemic detoxification. In addition, the
      implication of particle/toxin nanocomplexes in the development of toxoid vaccines
      is discussed. 

PMID- 25868456
TI  - Interdependence of initial cell density, drug concentration and exposure time
      revealed by real-time impedance spectroscopic cytotoxicity assay.
AB  - We investigated the combined effect of the initial cell density (12,500, 35,000,
      75,000, and 100,000 cells cm(-2)) and concentration of the anti-cancer drug
      doxorubicin on HeLa cells by performing time-dependent cytotoxicity assays using
      real-time electrochemical impedance spectroscopy. A correlation between the rate
      of cell death and the initial cell seeding density was found at 2.5 MUM
      doxorubicin concentration, whereas this was not observed at 5 or 100 MUM. By
      sensing the changes in the cell-substrate interaction using impedance
      spectroscopy under static conditions, the onset of cytotoxicity was observed 5 h
      earlier than when using a standard colorimetric end-point assay (MTS) which
      measures changes in the mitochondrial metabolism. Furthermore, with the MTS assay
      no cytotoxicity was observed after 15 h of incubation with 2.5 MUM doxorubicin,
      whereas the impedance showed at this time point cell viability that was below
      25%. These results indicate that impedance detection reveals cytotoxic events
      undetectable when using the MTS assay, highlighting the importance of combining
      impedance detection with traditional drug toxicity assays towards a more in depth
      understanding of the effect of anti-cancer drugs on in vitro assays. Moreover,
      the detection of doxorubicin induced toxicity determined with impedance under
      static conditions proved to be 6 times faster than in perfusion culture.

PMID- 25868457
TI  - Correction: Design of a robust superhydrophobic surface: thermodynamic and
      kinetic analysis.

PMID- 25868455
TI  - Free energetics of carbon nanotube association in aqueous inorganic NaI salt
      solutions: Temperature effects using all-atom molecular dynamics simulations.
AB  - In this study, we examine the temperature dependence of free energetics of
      nanotube association using graphical processing unit-enabled all-atom molecular
      dynamics simulations (FEN ZI) with two (10,10) single-walled carbon nanotubes in
      3 m NaI aqueous salt solution. Results suggest that the free energy, enthalpy and
      entropy changes for the association process are all reduced at the high
      temperature, in agreement with previous investigations using other hydrophobes.
      Via the decomposition of free energy into individual components, we found that
      solvent contribution (including water, anion, and cation contributions) is
      correlated with the spatial distribution of the corresponding species and is
      influenced distinctly by the temperature. We studied the spatial distribution and
      the structure of the solvent in different regions: intertube, intratube and the
      bulk solvent. By calculating the fluctuation of coarse-grained tube-solvent
      surfaces, we found that tube-water interfacial fluctuation exhibits the strongest
      temperature dependence. By taking ions to be a solvent-like medium in the absence
      of water, tube-anion interfacial fluctuation shows similar but weaker dependence
      on temperature, while tube-cation interfacial fluctuation shows no dependence in
      general. These characteristics are discussed via the malleability of their
      corresponding solvation shells relative to the nanotube surface. Hydrogen bonding
      profiles and tetrahedrality of water arrangement are also computed to compare the
      structure of solvent in the solvent bulk and intertube region. The hydrophobic
      confinement induces a relatively lower concentration environment in the intertube
      region, therefore causing different intertube solvent structures which depend on
      the tube separation. This study is relevant in the continuing discourse on
      hydrophobic interactions (as they impact generally a broad class of phenomena in
      biology, biochemistry, and materials science and soft condensed matter research),
      and interpretations of hydrophobicity in terms of alternative but parallel
      signatures such as interfacial fluctuations, dewetting transitions, and enhanced
      fluctuation probabilities at interfaces.

PMID- 25868458
TI  - The shape of dementia: new measures of morphological complexity in event-related
      potentials (ERP) and its application to the detection of Alzheimer's disease.
AB  - In this paper, we address the problem of quantifying the commonly observed
      disorganization of the stereotyped wave form of the ERP associated with the P300
      component in patients with Alzheimer's disease. To that extent, we propose two
      new measures of complexity which relate the spectral content of the signal with
      its temporal waveform: the spectral matching coefficient and the spectral
      matching entropy. We show by means of experiments that those measures effectively
      measure complexity and are related to the shape in an intuitive way. Those
      indexes are compared with commonly used measures of complexity when comparing AD
      patients against age-matched healthy controls. The results indicate that AD ERP
      signals are, indeed, more complex in the shape than that of controls, and this
      result is evidenced mainly by means of our new measures which have a better
      performance compared to similar ones. Finally, we try to explain this increase in
      complexity in light of the communication through coherence hypothesis framework,
      relating commonly found changes in the EEG with our own results. 

PMID- 25868459
TI  - Effectiveness and safety of thrombolytic therapy in elderly patients with
      pulmonary embolism.
AB  - Pulmonary embolism (PE) is a major cause of cardiovascular death. Thrombolytic
      therapy was shown to reduce mortality, especially in high risk patients. In
      elderly patients (>65 years old) with PE, thrombolytic therapy may be underused
      due to risk of hemorrhagic complications. In this study, we aimed to assess the
      effectiveness and safety of thrombolytic therapy among elderly patients with PE.
      363 patients (205 subjects in study group, 158 subjects in control group) who
      were admitted to our hospital with PE were enrolled to the study. The patients
      were divided into subgroups according to their age and treatment strategy.
      Mortality rates and bleeding complications according to TIMI bleeding criteria in
      30 days and 1-year were analyzed. In elderly patients, total mortality (7.8 vs.
      20.1 %, p = 0.05) and mortality at 1-year follow-up (1.9 vs. 12.9 %, p = 0.03)
      was significantly lower in patients who received thrombolytic treatment.
      Difference in total bleeding (9.8 vs. 4.5 %, p = 0.18) and major bleeding (3.9
      vs. 0.6 %, p = 0.10) in thrombolytic and non-thrombolytic groups was non
      significant. Thrombolytic therapy is associated with lower mortality and
      acceptable bleeding complication rates in PE patients older than 65 years old. 

PMID- 25868460
TI  - Strategies and outcomes of periprocedural bridging therapy with low-molecular
      weight heparin in patients with mechanical heart valves.
AB  - Patients with mechanical heart valves (MHV) undergoing invasive procedures often
      receive periprocedural bridging with low-molecular-weight heparin (LMWH). The
      bridging strategies used in real-life and the predictors for bleeding and
      thrombosis are not well studied. We retrospectively assessed patients with MHV
      that underwent invasive procedures requiring vitamin K antagonist interruption
      and LMWH bridging. Thromboembolic and bleeding events occurring up to 30 days
      after the procedures were recorded. Predictors of major bleeding events (MBEs)
      were analyzed with logistic regression. We evaluated 547 patients with MHV who
      underwent 275 procedures during a 6.5-year period. Bridging with LMWH was used in
      185 procedures in a total of 117 patients. Combined pre- and post-operative
      bridging was the most frequently employed (63 %). Doses of LMWH were prophylactic
      in 96 (52 %) of the procedures and therapeutic in 89 (48 %). The procedure
      related bleeding risk was evaluated as high in 70 (38 %) and low in 115 (62 %) of
      the procedures. There was a trend to more frequent use of prophylactic doses (61
      %) in high-risk surgery, and more therapeutic doses (53 %) in low-risk ones.
      There were 36 bleeding episodes, 21 (11 % of procedures) of which were classified
      as MBEs, but there were no thromboembolic events. Most MBEs (n = 14; 67 %)
      occurred in surgeries with high bleeding risk. In the multivariate analysis, the
      bleeding risk of the surgery itself was the only independent predictor for MBEs.
      For patients with MHV receiving perioperative bridging with LMWH, the major
      predictor for MBE is the bleeding risk of the surgery. 

PMID- 25868461
TI  - Biomarker Qualification: Toward a Multiple Stakeholder Framework for Biomarker
      Development, Regulatory Acceptance, and Utilization.
AB  - The discovery, development, and use of biomarkers for a variety of drug
      development purposes are areas of tremendous interest and need. Biomarkers can
      become accepted for use through submission of biomarker data during the drug
      approval process. Another emerging pathway for acceptance of biomarkers is via
      the biomarker qualification program developed by the Center for Drug Evaluation
      and Research (CDER, US Food and Drug Administration). Evidentiary standards are
      needed to develop and evaluate various types of biomarkers for their intended use
      and multiple stakeholders, including academia, industry, government, and
      consortia must work together to help develop this evidence. The article describes
      various types of biomarkers that can be useful in drug development and
      evidentiary considerations that are important for qualification. A path forward
      for coordinating efforts to identify and explore needed biomarkers is proposed
      for consideration. 

PMID- 25868462
TI  - Normalization of relative and incomplete temporal expressions in clinical
      narratives.
AB  - OBJECTIVE: To improve the normalization of relative and incomplete temporal
      expressions (RI-TIMEXes) in clinical narratives. METHODS: We analyzed the RI
      TIMEXes in temporally annotated corpora and propose two hypotheses regarding the
      normalization of RI-TIMEXes in the clinical narrative domain: the anchor point
      hypothesis and the anchor relation hypothesis. We annotated the RI-TIMEXes in
      three corpora to study the characteristics of RI-TMEXes in different domains.
      This informed the design of our RI-TIMEX normalization system for the clinical
      domain, which consists of an anchor point classifier, an anchor relation
      classifier, and a rule-based RI-TIMEX text span parser. We experimented with
      different feature sets and performed an error analysis for each system component.
      RESULTS: The annotation confirmed the hypotheses that we can simplify the RI
      TIMEXes normalization task using two multi-label classifiers. Our system achieves
      anchor point classification, anchor relation classification, and rule-based
      parsing accuracy of 74.68%, 87.71%, and 57.2% (82.09% under relaxed matching
      criteria), respectively, on the held-out test set of the 2012 i2b2 temporal
      relation challenge. DISCUSSION: Experiments with feature sets reveal some
      interesting findings, such as: the verbal tense feature does not inform the
      anchor relation classification in clinical narratives as much as the tokens near
      the RI-TIMEX. Error analysis showed that underrepresented anchor point and anchor
      relation classes are difficult to detect. CONCLUSIONS: We formulate the RI-TIMEX
      normalization problem as a pair of multi-label classification problems.
      Considering only RI-TIMEX extraction and normalization, the system achieves
      statistically significant improvement over the RI-TIMEX results of the best
      systems in the 2012 i2b2 challenge.

PMID- 25868463
TI  - NHS conference is warned of dangers of Transatlantic Trade and Investment
      Partnership.

PMID- 25868465
TI  - Benefits and barriers to the public health pharmacy: a qualitative exploration of
      providers' and commissioners' perceptions of the Healthy Living Pharmacy
      framework.
AB  - AIMS: The aims of this study were to explore the barriers to the implementation
      and progression of the Healthy Living Pharmacy (HLP) framework, from both
      provider and commissioner perspectives, and to ascertain whether the successes
      and barriers of the framework perceived by pharmacies are shared with
      commissioners. METHODS: A structured qualitative interview study, using purposive
      sampling, was undertaken with 11 community pharmacists and 11 Healthy Living
      Champions (providers) from HLPs in the north of England. Four commissioners of
      such services were also interviewed. Interviews were analysed using a thematic
      approach. RESULTS: There were many aspects of the HLP framework that the service
      'providers' were positive about, namely, workforce development, engagement
      (particularly with the smoking cessation service) and as a motivation for
      pharmacy teams. However, there were areas of concern about low awareness among
      pharmacy users, the time involved in delivery, as well as financial
      considerations. These were exemplified by the health checks element.
      Commissioners also expressed concerns about health checks as well as a lack of
      cohesion between commissioners and service providers and a poor understanding of
      the broader framework. CONCLUSION: The HLP framework was perceived as valuable by
      providers although there were areas of concern. A key barrier to the framework -
      perceived by both providers and commissioners - was the implementation of health
      checks. This should be considered in future commissioning.

PMID- 25868464
TI  - Genetic Evidence Supports a Major Role for Akt1 in VSMCs During Atherogenesis.
AB  - RATIONALE: Coronary artery disease, the direct result of atherosclerosis, is the
      most common cause of death in Western societies. Vascular smooth muscle cell
      (VSMC) apoptosis occurs during the progression of atherosclerosis and in advanced
      lesions and promotes plaque necrosis, a common feature of high-risk/vulnerable
      atherosclerotic plaques. Akt1, a serine/threonine protein kinase, regulates
      several key endothelial cell and VSMC functions including cell growth, migration,
      survival, and vascular tone. Although global deficiency of Akt1 results in
      impaired angiogenesis and massive atherosclerosis, the specific contribution of
      VSMC Akt1 remains poorly characterized. OBJECTIVE: To investigate the
      contribution of VSMC Akt1 during atherogenesis and in established atherosclerotic
      plaques. METHODS AND RESULTS: We generated 2 mouse models in which Akt1
      expression can be suppressed specifically in VSCMs before (Apoe(-/
      )Akt1(fl/fl)Sm22alpha(CRE)) and after (Apoe(-/-)Akt1(fl/fl)SM-MHC-CreER(T2E)) the
      formation of atherosclerotic plaques. This approach allows us to interrogate the
      role of Akt1 during the initial and late steps of atherogenesis. The absence of
      Akt1 in VSMCs during the progression of atherosclerosis results in larger
      atherosclerotic plaques characterized by bigger necrotic core areas, enhanced
      VSMC apoptosis, and reduced fibrous cap and collagen content. In contrast, VSMC
      Akt1 inhibition in established atherosclerotic plaques does not influence lesion
      size but markedly reduces the relative fibrous cap area in plaques and increases
      VSMC apoptosis. CONCLUSIONS: Akt1 expression in VSMCs influences early and late
      stages of atherosclerosis. The absence of Akt1 in VSMCs induces features of
      plaque vulnerability including fibrous cap thinning and extensive necrotic core
      areas. These observations suggest that interventions enhancing Akt1 expression
      specifically in VSMCs may lessen plaque progression.

PMID- 25868466
TI  - Cochlear Nerve Stimulation in the Internal Auditory Canal in Ossified Cochlea: A
      Case Study.
AB  - OBJECTIVE: To present the first reported case of intraneural direct cochlear
      nerve stimulation in a human being. STUDY DESIGN: This is a case report. RESULTS:
      A 23-year-old patient with bilateral progressive hearing loss associated with
      bilateral complete semicircular canal aplasia and ossified cochleas underwent
      cochlear implantation. During surgery, a patent cochlear lumen could not be
      found, and the array was positioned in the internal auditory canal adjacent to
      the cochlear nerve. Against our expectations, an assiduous rehabilitation and
      frequent fitting adjustments have led to a word recognition score, in open set
      speech with lip reading, of 18/25 and acceptable frequency discrimination.
      CONCLUSIONS: We are aware that this was an anomalous use of the cochlear implant,
      and it is not our aim to suggest a new indication for cochlear array positioning.
      However, this case shows that auditory perception, to some degree, can be
      obtained with intraneural direct cochlear nerve stimulation.

PMID- 25868467
TI  - Effect of exercise, heat stress and dehydration on myocardial performance.
AB  - BACKGROUND: Myocardial dysfunction is a well-documented outcome of extended
      periods of high cardiac output. Whether similar effects occur during
      firefighting, an occupation characterized by repeated periods of work compounded
      by dehydration and heat stress, is uncertain. AIMS: To investigate the
      independent and combined effects of moderate heat stress and dehydration on
      indicators of myocardial performance following intermittent, submaximal treadmill
      exercise while wearing personal protective equipment (PPE). METHODS: Twelve
      aerobically fit young men (age 21.5+/-2.6 years; maximal oxygen uptake [VO2max]
      60.3+/-4.4ml kg(-1) min(-1)) performed intermittent treadmill walking exercise
      consisting of three 20min bouts at an intensity of ~40% VO2max separated by two
      periods of rest in four different conditions in random order: (i) no heat stress
      euhydrated, (ii) heat stress-euhydrated (heat stress created by wearing PPE,
      (iii) no heat stress-dehydrated and (iv) heat stress-dehydrated. We measured core
      temperature by a telemetric gastrointestinal pill. We determined cardiac
      variables by standard echocardiographic techniques immediately before and ~30min
      after exercise. RESULTS: We recorded no significant changes in markers of
      systolic (ejection fraction, shortening fraction, tissue Doppler-S) or diastolic
      (mitral peak E velocity, tissue Doppler-E' and E/E') function following exercise
      in any of the four conditions. CONCLUSIONS: In this model of exercise designed to
      mimic the work, heat stress and dehydration associated with firefighting
      activities, we observed no negative effects on myocardial inotropic or lusitropic
      function.

PMID- 25868468
TI  - One-year clinical success of a 'no-bonus' freeze protocol using the second
      generation 28 mm cryoballoon for pulmonary vein isolation.
AB  - AIMS: Studies on the use of the second-generation 28 mm cryoballoon (CB) for the
      treatment of atrial fibrillation (AF) have reported superior 1-year clinical
      outcome. Customarily, a bonus freeze cycle is applied after pulmonary vein
      isolation (PVI). The purpose of the present study was to assess the 1-year
      clinical outcome following PVI foregoing a bonus freeze cycle. METHODS AND
      RESULTS: Patients with drug-refractory paroxysmal AF (PAF) or persistent AF
      underwent PVI using the second-generation 28 mm CB. The freeze cycle duration was
      set at 240 s. No bonus freeze cycle was applied. Clinical follow-up (FU) included
      12-lead ECGs and 24h-Holter ECGs at 3, 6, and 12 months. A total of 45 patients
      (age 60 +/- 11 years, mean LA diameter 42.1 +/- 8.6 mm, n = 38 [84%] PAF)
      underwent CB-based PVI. Of 177 pulmonary veins (PVs) identified, 176/177 (99%)
      PVs were successfully isolated. The mean number of CB applications was 1.2 +/-
      0.4, 1.5 +/- 0.8, 1.4 +/- 0.7, 1.1 +/- 0.3 and 1.7 +/- 1.2 for the right superior
      PVs, right inferior PVs, left superior PVs, left inferior PVs, and left common
      PVs, respectively. Mean procedure and fluoroscopy times were 113 +/- 32 and 19 +/
      7 min, respectively. Phrenic nerve palsy occurred in 1/45 (2%) patients. One of
      45 (2%) patients was lost to FU. After a mean FU period of 392 +/- 58 (267-522)
      days including a 3-month blanking period, 36 of 44 (82%) patients remained in
      stable sinus rhythm. Five out of eight patients with arrhythmia recurrence
      underwent a second procedure. Only those PVs isolated with a single freeze cycle
      (5/11 PVs, 45%) demonstrated PV reconduction. In contrast, no PV reconnection was
      found in PVs initially treated with multiple freeze cycles. CONCLUSIONS: A 'no
      bonus'-freeze protocol for PVI using the second-generation 28 mm CB resulted in
      an 82% 1-year clinical success rate. A bonus freeze cycle following successful
      PVI may not be essential to superior clinical outcome.

PMID- 25868469
TI  - Cost-effectiveness of mass screening for untreated atrial fibrillation using
      intermittent ECG recording.
AB  - AIMS: The aim of this study was to estimate the cost-effectiveness of 2 weeks of
      intermittent screening for asymptomatic atrial fibrillation (AF) in 75/76-year
      old individuals. METHODS AND RESULTS: The cost-effectiveness analysis of
      screening in 75-year-old individuals was based on a lifelong decision analytic
      Markov model. In this model, 1000 hypothetical individuals, who matched the
      population of the STROKESTOP study, were simulated. The population was analysed
      for different parameters such as prevalence, AF status, treatment with oral
      anticoagulation, stroke risk, utility, and costs. In the base-case scenario,
      screening of 1000 individuals resulted in 263 fewer patient-years with undetected
      AF. This implies eight fewer strokes, 11 more life-years, and 12 more quality
      adjusted life years (QALYs) per 1000 screened individuals. The screening implies
      an incremental cost of ?50 012, resulting in a cost of ?4313 per gained QALY and
      ?6583 per avoided stroke. CONCLUSIONS: With the use of a decision analytic
      simulation model, it has been shown that screening for asymptomatic AF in 75/76
      year-old individuals is cost-effective.

PMID- 25868470
TI  - Synergy of cancer immunotherapy and radiotherapy.

PMID- 25868472
TI  - Erratum.

PMID- 25868474
TI  - Trichosides A and B, new withanolide glucosides from Tricholepis eburnea.
AB  - Trichosides A (1) and B (2), new withanolide glucosides, have been isolated from
      the n-butanolic fraction of the 75% methanolic extract of aerial parts of
      Tricholepis eburnea. Their structures were elucidated through spectroscopic
      analysis including ESI-MS, 2D NMR and acid hydrolysis.

PMID- 25868475
TI  - Beneficial Effects of Rhodotorula sp. C11 on Growth and Disease Resistance of
      Juvenile Japanese Spiky Sea Cucumber Apostichopus japonicus.
AB  - The purpose of this study was to evaluate the effects of dietary administration
      of the live yeast, Rhodotorula sp. C11, on growth and disease resistance against
      Vibrio splendidus infection in juvenile Japanese spiky sea cucumber Apostichopus
      japonicus. Sea cucumbers were fed diets containing Rhodotorula sp. C11 at 0
      (control), 104, 105, and 106 CFU/g of feed for 45 d. There were three replicate
      tanks per dietary treatment. The specific growth rates were higher in all sea
      cucumbers treated with Rhodotorula sp. C11 than in the controls. Following a
      challenge with V. splendidus NB13, the cumulative prevalence and mortality of sea
      cucumbers fed diets supplemented with Rhodotorula sp. C11 were lower than in
      animals fed the basal diet. In sea cucumbers fed diets supplemented with
      Rhodotorula sp. C11 for 42 d, the only viable yeast found in the intestine was
      Rhodotorula sp. C11, which had counts of 1.58-1.98 * 104CFU/g. No yeast was
      isolated from the intestine of animals fed the basal diet. For the colonization
      study, 20 sea cucumbers from each dietary treatment were removed to separate
      tanks and fed the control diet from day 16 to day 46. The viable yeast
      (Rhodotorula sp. C11) counts in the intestine decreased to 60-80 CFU/g by day 37.
      Moreover, as demonstrated by denaturing gradient gel electrophoresis, Rhodotorula
      sp. C11 colonization of the intestine could be detected until day 46. The
      differences in culture and PCR-denaturing gradient gel electrophoresis may be due
      to differences in the sensitivity of both methods. The present result showed that
      Rhodotorula sp. C11 was able to successfully colonize the intestine of juvenile
      Japanese spiky sea cucumbers by dietary supplementation, which improved its
      growth and disease resistance.

PMID- 25868473
TI  - Influence of severity of illness on neutrophil gelatinase-associated lipocalin
      performance as a marker of acute kidney injury: a prospective cohort study of
      patients with sepsis.
AB  - BACKGROUND: The role of neutrophil gelatinase-associated lipocalin (NGAL) as a
      diagnostic marker for acute kidney injury (AKI) in sepsis is still debated. We
      hypothesized that in sepsis, the performance of serum(s) and urinary(u) NGAL can
      be negatively impacted by severity of illness and inflammation, and that both
      uNGAL and sNGAL levels can be increased regardless of presence of AKI. METHODS:
      One hundred and seven patients with sepsis were included. uNGAL and sNGAL were
      measured at admission (T0) and 4 hours (T4) and 24 hours later (T24). Transient
      and intrinsic AKI were respectively defined as AKI according to RIFLE during the
      first 72 hours that did or did not recover to "no AKI" in the following 72 hours.
      Patients were classified according to tertiles of CRP and APACHE II score
      increase. The relationship between sNGAL and uNGAL was assessed by linear
      regression. RESULTS: Fifty-seven patients developed transient and 22 intrinsic
      AKI. Prevalence of transient and intrinsic AKI were higher in patients with
      versus without septic shock (OR (95% CI): 3.3(1.4-8.2)). uNGAL was associated
      with sNGAL, and this with parallel slopes but different intercepts for AKI (Y =
      0.87*X + 314.3, R2 = 0.31) and no AKI (Y = 0.87*X + 20.1, R2 = 0.38). At T4,
      median uNGAL and sNGAL levels were higher in septic patients with versus without
      shock but this is independent of AKI ((545 ng/mL vs 196 ng/ml for uNGAL and 474
      ng/ml vs 287 ng/ml for sNGAL (both P = 0.003)). Both uNGAL and sNGAL levels
      increased with tertiles of CRP and APACHE II score increase. CONCLUSIONS: Serum
      and uNGAL levels are influenced by severity of illness and inflammation, and this
      was found to be independent of the presence of AKI. There is a strong correlation
      between sNGAL and uNGAL levels in patients with sepsis, indicating that increased
      levels of uNGAL can also be due to overspill from the systemic circulation,
      blurring the discriminative value of NGAL as a biomarker for AKI in patients with
      sepsis.

PMID- 25868477
TI  - A density functional theory based study of the electron transfer reaction at the
      cathode-electrolyte interface in lithium-air batteries.
AB  - The unique properties of ionic liquids such as a relatively wide electrochemical
      stability window and very low vapor pressure have made them promising candidates
      as electrolytes for improving the cyclic performance of lithium-air batteries.
      The local current density, which is an important parameter in determining the
      performance of lithium-air batteries, is a function of the rate constant of the
      electron transfer reactions at the surface of the cathode. In this study, a novel
      method based on Marcus theory is presented to investigate the effect of varying
      the length of the alkyl side chain of model imidazolium based cations and the
      operating temperature on the rates of electron transfer reactions at the cathode.
      The necessary free energies of all the species involved in the multi-step
      reduction of oxygen into the peroxide ion were calculated using density
      functional theory (DFT). Our results indicate that the magnitude of the Gibbs
      free energy for the reduction of oxygen into the superoxide ion and also for the
      reduction of superoxide into the peroxide ion increases with an increase in the
      static dielectric constant of the ionic liquid. This trend in turn corresponds to
      the decrease in the length of the alkyl side chain of the ionic liquid cation.
      Furthermore, the change in Gibbs free energy decreases with increase in the
      operating temperature. The inner-sphere reorganization energies were evaluated
      using Nelsen's four point method. The total reorganization energies of all
      reduction reactions increase with decrease in the length of the alkyl side chain
      and increase in the operating temperature. Finally, the rate constants of the
      electron transfer reaction involved in the reduction of oxygen were calculated.
      The logarithm of the reaction rate constants decreases with increase in the
      static dielectric constant and increases with increase in the operating
      temperature. Our results provide fundamental insight into the kinetics and
      thermodynamics of the electron transfer reactions at the cathode that will help
      in the identification of appropriate electrolytes for enhanced performance of
      lithium-air batteries. 

PMID- 25868476
TI  - Best vaccination practice and medically attended injection site events following
      deltoid intramuscular injection.
AB  - Analysis of medically attended injection site events data provides a vehicle to
      appreciate the inadequacies of vaccination practice for deltoid intramuscular
      injection and to develop best practice procedures. These data can be divided into
      3 groups; nerve palsies, musculoskeletal injuries and cutaneous reactions and
      reflect inappropriate site of injection, needle over or under penetration, local
      sepsis and vascular complications. The aim of this review is to formulate best
      vaccination practice procedures for deltoid intramuscular injection of vaccines
      through the collation and analysis of medically attended injection site events.

PMID- 25868478
TI  - XPS of guanidinium ionic liquids: a comparison of charge distribution in
      nitrogenous cations.
AB  - Herein, we investigate the first X-ray photoelectron spectroscopy (XPS) data for
      a range of functionalised guanidinium based systems that are commonly employed in
      the dissolution of biomolecules. We define a peak fitting model which allows the
      direct comparison to more common cation sets including dialkyl-imidazolium,
      pyrrolidinium, and quaternary ammonium based systems. The measured binding
      energies (BEs) of the N 1s and C 1s components are presented and notable
      variations discussed. These data show a large difference between measured binding
      energies for the Ncation 1s when compared to other families of ionic liquids.
      These results suggest a weaker anion/cation interaction thus the anion is more
      able to interact with a solid matrix, i.e. keratin, silk, chitin, collagen,
      cellulose, and become more active in dissolution. 

PMID- 25868480
TI  - Gallium maltolate as an alternative to macrolides for treatment of presumed
      Rhodococcus equi pneumonia in foals.
AB  - BACKGROUND: Macrolide-resistant isolates of Rhodococcus equi are emerging,
      prompting the search for clinically effective alternative antimicrobials.
      HYPOTHESIS: The proportion of foals with ultrasonographic evidence of pneumonia
      presumed to be caused by R. equi that had a successful outcome when administered
      gallium maltolate (GaM) PO would not be more than 10% inferior (ie, lower) than
      that of foals receiving standard treatment. ANIMALS: Fifty-four foals with
      subclinical pulmonary abscesses among 509 foals at 6 breeding farms in Kentucky.
      METHODS: Controlled, randomized, prospective noninferiority study. Foals with
      ultrasonographic lesions >1 cm in diameter (n = 54) were randomly allocated to
      receive per os either clarithromycin combined with rifampin (CLR+R) or GaM, and
      followed up for 28 days by daily physical inspections and weekly (n = 1 farm) or
      biweekly (n = 4 farms) thoracic ultrasound examinations by individuals unaware of
      treatment-group assignments. Treatment success was defined as resolution of
      ultrasonographically identified pulmonary abscesses within 28 days of initiating
      treatment. Noninferiority was defined as a 90% confidence interval for the
      observed difference in CLR+R minus GaM that was <=10%. RESULTS: The proportion of
      GaM-treated foals that resolved (70%; 14/20) was similar to that of foals treated
      with CLR+R (74%; 25/34), but we failed to demonstrate noninferiority for GaM
      relative to CLR+R; however, GaM was noninferior to CLR+R treatment when results
      from a noncompliant farm were excluded. CONCLUSIONS AND CLINICAL IMPORTANCE:
      Gallium maltolate is not inferior to macrolides for treating foals with
      subclinical pneumonia. Use of GaM might reduce pressure for macrolide-resistance
      in R. equi.

PMID- 25868481
TI  - Development of a real-time loop-mediated isothermal amplification assay for the
      sensitive and rapid detection of Listeria monocytogenes.
AB  - A real-time loop-mediated isothermal amplification (RealAmp) assay for the
      detection of Listeria was developed. The RealAmp assay, using primers specific
      for the hemolysin-encoding hlyA gene, was verified using Listeria monocytogenes
      strains (n = 58) from different regions of the world. Both the sensitivity and
      specificity of the RealAmp assay were high. The RealAmp assay could detect 10(3)
      CFU ml(-1) within 30 min. A comparative evaluation of the RealAmp assay, the API
      Listeria assay, and the real-time PCR assay revealed that the RealAmp assay is
      simpler, faster, and has a higher specificity than the other two assays.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Conventional culture and molecular
      detection methods are always time consuming and require a specific laboratory
      infrastructure, thereby restricting their use for the rapid detection and
      diagnosis of pathogens. A real-time loop-mediated isothermal amplification
      (RealAmp) assay performed by ESEtube scanner to rapidly detect Listeria
      monocytogenes isolated from food was developed. The results showed that the
      RealAmp assay using the tube scanner was more efficient and precise than the
      conventional API Listeria assay and the real-time PCR assay.

PMID- 25868483
TI  - Laparoscopic primary repair and isoperistaltic endoluminal drain for Boerhaave's
      Syndrome.
AB  - Spontaneous oesophageal rupture, also known as Boerhaave syndrome (BS), is a rare
      and potentially lethal pathological condition. BS recognition is difficult, while
      rapidity of diagnosis, along with extension of the lesion, affects type and
      outcome of treatment. BS was classically treated by thoracotomy, but laparoscopic
      (LS), thoracoscopic (TS) surgery, and nonsurgical procedures as endoscopic stent
      positioning or use of glues have been described. Still, there is no model
      treatment, and selection of the most appropriate therapeutic procedure is complex
      in the absence of standardised criteria. We successfully managed a patient
      affected with BS by LS approach and present our experience along with a review of
      treatment options so far described. Our treatment integrated positioning of an
      oesophageal isoperistaltic endoluminal drain (IED), that we routinely use in
      oesophageal sutures at risk of leakage, and of which there is no previous report
      in the setting of BS. A 68 year old man presented to our attention with true BS,
      suspected on chest-abdominal CT scan and confirmed by upper GI contrast swallow
      test, showing leakage of hydro-soluble contrast from the lower third of the
      oesophagus. Of note, pleural cavities appeared intact. We performed an urgent
      laparoscopy 12 hours after the onset of symptoms. Laparoscopic toilet of the
      inferior mediastinum and dual layer oesophageal repair with pedicled omental flap
      were complemented by positioning of IED, feeding jejunostomy and two tubular
      drains. The patient had a slow but consistent recovery where IED played as a
      means of oesophageal suture protection, until he could be discharged home. We
      think that, when integrity of the pleura is documented, LS should be priority
      choice to avoid contamination of the pleural cavities. We have to consider every
      type of oesophageal repair in BS at risk of failure, and every means of
      protection of the suture is opportune. In our patient the oesophageal suture,
      covered with a flap of omentum isolated on a pedicle, has also been protected
      from excessive oesophageal endoluminal pressures by means of a multi-fenestrated
      two way endooesophageal drain (IED, two way tube type Salem). Oesophageal drain
      has the finality of relieving tension and monitoring the healing of the
      oesophageal repair.

PMID- 25868484
TI  - Effects of two physical exercise protocols on physical performance related to
      falls in the oldest old: A randomized controlled trial.
AB  - AIM: To compare the effects of 16-week multicomponent and resistance training,
      and 6-week detraining on physical variables related to a higher risk of falls in
      very old people. METHODS: A randomized, three-arm, controlled trial was carried
      out. A total of 69 community-dwelling older adults aged 80 years and older were
      allocated to three groups: control, multicomponent training and resistance
      training. They were assessed at baseline, after 16-week training and 6-week
      detraining. The control group did not perform any intervention. The
      multicomponent group performed protocol consisting of warm-up, aerobic, strength,
      balance and cool-down exercises. The resistance group underwent strength
      exercises using six adapted machines. The training sessions had progressive
      intensity, lasted 16 weeks and 12 included three 1-h sessions per week. The
      assessment consisted of anamneses, five-repetition sit-to-stand, one-leg
      standing, tandem and dual task tests. For statistical analysis, alpha = 0.05 was
      used. RESULTS: There were no significant differences between groups and
      assessments in any variable when analyzed by intention to treat. However, when
      analyzed, the older adults who adhered to the training, the multicomponent group,
      had a significant improvement in the sit-to-stand and the one-leg standing (right
      support) tests. There was a significant main effect between times on the one-leg
      standing (left support) test. CONCLUSION: In very old people, multicomponent
      training seems to be more beneficial and presents fewer adverse events when the
      adherence to protocol is higher.

PMID- 25868486
TI  - Promoting the role of pharmacists in chronic pain management: how can we make an
      impact on policy and practice?

PMID- 25868485
TI  - Prognostic value of interim FDG-PET in Hodgkin lymphoma: systematic review and
      meta-analysis.
AB  - This study aimed to systematically review and meta-analyse the value of interim
      (18) F-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) in
      predicting treatment failure in Hodgkin lymphoma. MEDLINE was systematically
      searched for original studies that used standardized international criteria for
      interim FDG-PET interpretation. Included studies were methodologically assessed.
      Summary receiver operating characteristic (sROC) analysis was performed, and
      pooled sensitivity and specificity were calculated using a random effects model.
      Heterogeneity in diagnostic odds ratios (DORs) across studies was assessed and
      potential sources for inter-study heterogeneity were explored using subgroup
      analyses. Ten studies, comprising a total of 1389 Hodgkin lymphoma patients, were
      included. Sensitivity, specificity, positive predictive value and negative
      predictive value of interim FDG-PET for predicting treatment failure ranged
      between 0.0-81.5%, 72.2-96.6%, 0.0-86.0% and 84.4-98.6%, respectively. The area
      under the sROC curve was 0.877. Pooled sensitivity and specificity were 70.8%
      [95% confidence interval (CI): 64.7-76.4%] and 89.9% (95% CI: 88.0-91.6%). There
      was heterogeneity in DORs across individual studies (I2 = 72.7). The overall
      prognostic value of interim FDG-PET appears to be moderate for excluding and
      relatively high for identifying treatment failure in Hodgkin lymphoma. However,
      interim FDG-PET cannot yet be implemented in routine clinical practice due to
      moderate-quality evidence and inter-study heterogeneity that cannot be fully
      explained yet.

PMID- 25868487
TI  - Development of a collaborative professional group for HIV pharmacists: experience
      from the Canadian HIV/AIDS Pharmacists Network.

PMID- 25868488
TI  - Intracellular Self-Assembly and Disassembly of (19)F Nanoparticles Confer
      Respective "Off" and "On" (19)F NMR/MRI Signals for Legumain Activity Detection
      in Zebrafish.
AB  - (19)F MRI has higher selectivity but lower sensitivity than (1)H MRI for in vivo
      diagnosis. Therefore, to avoid using a high injection dose of the (19)F probe
      while, in the meantime, maintaining the high sensitivity of (19)F MRI has
      remained challenging. Local self-assembly and disassembly of (19)F nanoparticles
      could be one of the "smart" strategies to achieve this goal. Herein, we report a
      dual-functional probe 1 for glutathione (GSH)-controlled self-assembly and
      subsequent legumain (Lgmn)-controlled disassembly of its nanoparticles (i.e., 1
      NPs). Self-assembly and disassembly of 1-NPs confer (19)F magnetic resonance (MR)
      signals "off" and "on", respectively. Employing this strategy, we successfully
      applied 1 for consecutive detections of GSH and Lgmn in vitro and in cells,
      imaging Lgmn activity in HEK 293T tumors in zebrafish at a low dosage under 14.1
      T. 

PMID- 25868489
TI  - Mass-gathering Medicine: Risks and Patient Presentations at a 2-Day Electronic
      Dance Music Event.
AB  - INTRODUCTION: Music festivals, including electronic dance music events (EDMEs),
      increasingly are common in Canada and internationally. Part of a US $4.5 billion
      industry annually, the target audience is youth and young adults aged 15-25
      years. Little is known about the impact of these events on local emergency
      departments (EDs). METHODS: Drawing on prospective data over a 2-day EDME, the
      authors of this study employed mixed methods to describe the case mix and
      prospectively compared patient presentation rate (PPR) and ambulance transfer
      rate (ATR) between a first aid (FA) only and a higher level of care (HLC) model.
      RESULTS: There were 20,301 ticketed attendees. Seventy patient encounters were
      recorded over two days. The average age was 19.1 years. Roughly 69% were female
      (n=48/70). Forty-six percent of those seen in the main medical area were under
      the age of 19 years (n=32/70). The average length of stay in the main medical
      area was 70.8 minutes. The overall PPR was 4.09 per 1,000 attendees. The ATR with
      FA only would have been 1.98; ATR with HLC model was 0.52. The presence of an on
      site HLC team had a significant positive effect on avoiding ambulance transfers.
      DISCUSSION: Twenty-nine ambulance transfers and ED visits were avoided by the
      presence of an on-site HLC medical team. Reduction of impact to the public health
      care system was substantial. CONCLUSIONS: Electronic dance music events have
      predictable risks and patient presentations, and appropriate on-site health care
      resources may reduce significantly the impact on the prehospital and emergency
      health resources in the host community.

PMID- 25868490
TI  - Correction: Equilibrium gels of low-valence DNA nanostars: a colloidal model for
      strong glass formers.

PMID- 25868491
TI  - Application of gas-diffusion microextraction to solid samples using the
      chromatographic determination of alpha-diketones in bread as a case study.
AB  - Gas-diffusion microextraction (GDME) was applied to the extraction of vicinal
      diketones in bread samples aimed at the determination of these compounds by high
      performance liquid chromatography with ultraviolet detection (HPLC-UV). For the
      first time, GDME was used for direct chemical determination in solid samples,
      i.e. avoiding any sample preparation prior to extraction. Different extraction
      parameters were studied and optimized, namely temperature, time and chemical
      composition of the acceptor solution where o-phenylenediamine was used as a
      derivatizing agent, originating quinoxalines that could be determined at 315 nm.
      GDME demonstrated to be a good tool for the sampling of volatile compounds in
      solid samples with suitable method features for butane-2,3-dione (diacetyl, DC),
      pentane-2,3-dione (PN) and hexane-2,3-dione (HX): low LODs (6.0, 8.6 and 12 MUg
      kg(-1), for DC, PN and HX respectively) and LOQs (20, 29 and 38 MUg kg(-1), for
      DC, PN and HX respectively), r(2) above 0.990, and CV around 5%. The developed
      methodology was applied to the determination of different bread samples and was
      used to reveal the decrease of alpha-diketones in bread during the timeframe of a
      week. 

PMID- 25868492
TI  - Osteoimmunology: IgG immune complexes directly regulate bone homeostasis.

PMID- 25868493
TI  - Osteoarthritis: SIRT6 prevents chondrocyte senescence and DNA damage.

PMID- 25868494
TI  - Quantum Hall effect on top and bottom surface states of topological insulator
      (Bi1-xSbx)2Te3 films.
AB  - The three-dimensional topological insulator is a novel state of matter
      characterized by two-dimensional metallic Dirac states on its surface. To verify
      the topological nature of the surface states, Bi-based chalcogenides such as
      Bi2Se3, Bi2Te3, Sb2Te3 and their combined/mixed compounds have been intensively
      studied. Here, we report the realization of the quantum Hall effect on the
      surface Dirac states in (Bi1-xSbx)2Te3 films. With electrostatic gate-tuning of
      the Fermi level in the bulk band gap under magnetic fields, the quantum Hall
      states with filling factor +/-1 are resolved. Furthermore, the appearance of a
      quantum Hall plateau at filling factor zero reflects a pseudo-spin Hall insulator
      state when the Fermi level is tuned in between the energy levels of the non
      degenerate top and bottom surface Dirac points. The observation of the quantum
      Hall effect in three-dimensional topological insulator films may pave a way
      toward topological insulator-based electronics. 

PMID- 25868496
TI  - Editorial.

PMID- 25868495
TI  - Comparison of Socio-Demographic Characteristics of a Computer Based Breastfeeding
      Educational Intervention Among Rural Hispanic Women.
AB  - Examine association between socio-demographic characteristics and breastfeeding
      knowledge, self-efficacy and breastfeeding attrition prediction among rural
      Hispanic women. 46 rural Hispanic women, aged 18-38 years were enrolled from
      Regional West Medical Center, Scottsbluff, Nebraska. Intervention (n = 23) and
      attention control groups (n = 23) received bi-lingual breastfeeding education
      using touch screen computer and printed educational material. Participants were
      enrolled during last 6 weeks of pregnancy. Follow up assessments were at days 3
      and 7, weeks 2 and 6, and months 3 and 6 postpartum. More than half of
      participants were single and had 10-12 years of education. Less than half of them
      had ever breastfed their children. No differences in knowledge, self-efficacy and
      intent to breastfeed scores were seen between two groups. Significant positive
      association was seen between self-efficacy and intent to breastfeed. Self
      efficacy is an important predictor of intent to breastfeed among rural Hispanic
      women. 

PMID- 25868497
TI  - The invisible sentry : Radiological imaging in terror and terror prevention.
AB  - Radiological imaging may enable the recognition and documentation of acts of
      terror. Search by X-rays can assist in the detection of weapons, drugs,
      contraband, and hidden persons. Fluoroscopy, backscatter imaging, and computed
      tomography are being employed for the evaluation of luggage, humans, trucks, and
      containers. The identification of drugs and explosives is possible by additional
      spectral analysis. The images can show individuals nearly naked, which may lead
      to a discussion on violation of privacy and dignity. There are, however, clinical
      questions raised about the exposure to X-rays and the possible absence of
      informed consent. Finally, although the use of X-rays is part of terror
      prevention, it has been part of the terror, too. The Stasi, the secret service of
      the German Democratic Republic, used diagnostic X-rays and ionizing radiation in
      order to control opponents of the political system. 

PMID- 25868498
TI  - Cannabis and cardiotoxicity.
AB  - Cannabis is the most commonly consumed illicit drug. It is estimated that 4% of
      the global population between the ages of 15 and 64 smoked marijuana in 2003.
      Despite the drug's extreme popularity, reports of cannabis-related stroke and
      myocardial infarction are so rare as to still be reportable. Cannabinoids, the
      active compounds contained in marijuana, interact with cardiovascular centers in
      the brain, but also exert direct effects on vascular tone. Recent animal and in
      vitro studies have yielded conflicting results, some suggesting minimal effect,
      others suggesting that cannabinoids may be potent myocardial depressants. The
      observation that cardiotoxicity has never been reported in cancer patients taking
      dronabinol, the synthetic form of THC, tends to suggest that animal studies may
      have overstated the cardiovascular risk, which is probably comparable to that of
      smoking cigarettes. 

PMID- 25868499
TI  - 19th-century pathology : The examination of 83 vault-interred bodies.
AB  - Eighty-three bodies that had been inhumed in airtight lead coffins for more than
      150 years were subjected to postmortem examinations that included histological,
      dental, and microbiological studies. Preservation of internal structures was
      excellent in 29 cases, and moderate to good in 10. Skin and external features
      were well preserved in 10 other cases. The remaining bodies were reduced to
      skeletons. There was identifiable pathology in the majority of the well-preserved
      cases. In several bodies, more than one disease was present. It was possible to
      correlate the pathological findings with contemporary diagnoses in 10 cases. 

PMID- 25868500
TI  - Inflicted ano-genital injuries in children : Physical abuse or sexual abuse?
AB  - The ano-genital findings of two young children who died as a result of inflicted
      head injury are reported. These injuries were severe enough to lead to an initial
      suspicion that sexual abuse had also occurred as part of the fatal assault. When
      further history was available, the injuries were found to be the result of
      inflicted physical injury. 

PMID- 25868501
TI  - 9/11 and the new york city office of chief medical examiner.
AB  - On September 11, 2001 two hijacked airplanes struck the Twin Towers at the World
      Trade Center in New York City. All of the remains (19,915) were examined by the
      Office of Chief Medical Examiner (OCME) of New York City. The major goals of the
      OCME were to accurately identify the decedents and to promptly issue death
      certificates. As of September 2005, there were 1594 identifications of a total of
      2749 people reported missing. Of these, 976 were identified by a single means,
      which included DNA analysis in 852 of the victims. Use of legal statues can
      assist in the timely issuance of death certificates in mass fatalities, which
      benefit surviving family members. DNA analysis markedly improves the ability to
      identify remains and has become the standard method for identification in these
      types of disasters. Certain postmortem tissue samples are better suited for DNA
      analysis and yield better results than others. 

PMID- 25868502
TI  - Rape and attempted rape in Aarhus County, Denmark Police reported and unreported
      cases.
AB  - The aim of this study was to compare medical and nonmedical findings in police
      reported and unreported cases of rape and attempted rape in the county of Aarhus,
      Denmark, and to explore whether legal outcomes were influenced by medico-legal
      findings in the cases reported to the police.Data on rapes and attempted rapes
      were collected from the files of the Department of Forensic Medicine, police
      reports, and court files. Eighty-seven victims of alleged rape and attempted rape
      were included in a 14-month period. Of these, 60% were categorized as date rapes,
      23% as stranger rapes, and 16% as partner rapes. Sixteen percent did not report
      the alleged crime to the police, but still participated in a medico-legal
      examination. Twenty-nine percent filed police reports, but did not have a medico
      legal examination undertaken.Extra-genital lesions were more common among the
      women who filed police reports (63 vs 43%). Women who weee subjected to date rape
      and partner rape and had not suffered physical injuries were more reluctant to
      report to the police. Twelve cases were taken to court; 11 offenders were
      convicted with 1 acquitted. The presence of injuries, vaginal penetration, or the
      findings of semen, in this study, had not in fluenced the legal outcome. 

PMID- 25868503
TI  - Individualization of earprints : Variation in prints of monozygotic twins.
AB  - This article presents a study of the variation in the appearance of earprints
      from six pairs of monozygotic (MZ) twins, applying different methods with varying
      degrees of objectivity. By analyzing prints of MZ twins, we purposely select
      pairs of individuals for whom the degree of interindividual variation is low. We
      first provide an account of the corresponding characteristics and the differences
      that occur between prints from the individual members. We evaluate differences in
      both content (i.e., presence, shape, and intensity of imprinted features) and
      geometry (i.e., position of imprinted features). Differences are visualized by
      way of digital overlays. Differences in geometry are further evaluated by
      performing a hierarchical cluster analysis using variables derived from the
      position of seemingly corresponding features. As a next step, we explore a method
      to fully automatically analyze prints. In this approach, image regions are
      selected and matched automatically. A suggestion on how to apply this method to
      calculate the evidential value of an earprint is provided. To our knowledge, this
      is the first time that any method capable of fully automated earprint comparisons
      has been presented in the literature. 

PMID- 25868504
TI  - Examination and identification of a Danish 17th-century nobleman, Laurids Ebbesen
      : A multidisciplinary study.
AB  - Skeletal remains from a crypt in Aarhus Cathedral, where an 87-year-old Danish
      nobleman, Laurids Ebbesen, was thought to have been buried in 1696 were examined
      by a multidisciplinary team of investigators. Examination of clothing revealed a
      burial cap, indicating that he had been a nobleman. Using transition analysis of
      various bones, the age was estimated at around 82 years (95% confidence interval:
      70-92 years). The gender was male. The cranium showed an old, healed fracture in
      the left temporal region and there was arthritic damage of the vertebral column.
      In the chapel there were four statues of Laurids Ebbesen (and his three wives).
      Superimoposition of photographs of Ebbesen's head from the figures onto X-ray and
      computed tomography images of the skull confirmed that the cranium and the
      skeleton could have been that of Laurids Ebbesen. Thus, the involvement of a
      number of disciplines resulted in accurate dating of the burial; determination of
      the age, gender, an social status of the deceased individual; exclusion of other
      possible individuals; and comparison of the skull with an image of the deceased. 

PMID- 25868505
TI  - Practical issues involved in setting up temporary mortuaries after mass
      disasters.
AB  - Events involving terrorist bombings in Bali, Indonesia in 2002 and the earthquake
      with resultant Tsunami in Southern Asia in late 2004 have necessitated
      international collaborative efforts in massive disaster victim identification
      exercises. A critical issue involves speedy and accurate identification of the
      dead with repatriation to their country of origin. An essential requirement for
      this process is the establishment of effective and functinal mortuaries to enable
      systematic processing of the victims with appropriate documentation and quality
      control processes to ensure that identifications are correct and that processes
      are capable of audit. The following article outlines steps that need to be taken
      to set up temporatory mortuaries under such circumstances, possible problems that
      may be encountered, and suggested solutions. 

PMID- 25868507
TI  - Ba'alat.

PMID- 25868506
TI  - Forensic DNA on the internet.
AB  - The shear number of websites a vailable addressing the topic of forensic DNA
      investigation can make the search for specific information time-consuming and
      frustrating. This review aims to relieve this tension by drawing the reader's
      attention to a small number of well-produced and maintained websites covering
      major aspects of the forensic DNA field in genomic and Y chromosome short-tandem
      repeats and mitochondrial DNA analysis. 

PMID- 25868508
TI  - Husbands' and Wives' Physical Activity and Depressive Symptoms: Longitudinal
      Findings from the Cardiovascular Health Study.
AB  - BACKGROUND: When examining older adults' health behaviors and psychological
      health, it is important to consider the social context. PURPOSE: The purpose of
      this study was to examine in older adult marriages whether each spouse's physical
      activity predicted changes in their own (actor effects) and their partner's
      (partner effects) depressive symptoms. Gender differences were also examined.
      METHOD: Each spouse within 1260 married couples (at baseline) in the
      Cardiovascular Health Study completed self-report measures at wave 1 (1989-1990),
      wave 3 (1992-1993), and wave 7 (1996-1997). Dyadic path analyses were performed.
      RESULTS: Husbands' physical activity significantly predicted own decreased
      depressive symptoms (actor effect). For both spouses, own physical activity did
      not significantly predict the spouse's depressive symptoms (partner effects).
      However, husbands' physical activity and depressive symptoms predicted wives'
      physical activity and depressive symptoms (partner effects), respectively.
      Depressive symptoms did not predict physical activity. CONCLUSION: Findings
      suggest that husbands' physical activity is particularly influential for older
      married couples' psychological health.

PMID- 25868509
TI  - Association between change in body weight after midlife and risk of hip fracture
      the Singapore Chinese Health Study.
AB  - The relationship between change in body weight and risk of fractures is
      inconsistent in epidemiologic studies. In this cohort of middle-aged to elderly
      Chinese in Singapore, compared to stable weight, weight loss >=10 % over an
      average of 6 years is associated with nearly 40 % increase in risk of hip
      fracture. INTRODUCTION: Findings on the relationship between change in body
      weight and risk of hip fracture are inconsistent. In this study, we examined this
      association among middle-aged and elderly Chinese in Singapore. METHODS: We used
      prospective data from the Singapore Chinese Health Study, a population-based
      cohort of 63,257 Chinese men and women aged 45-74 years at recruitment in 1993
      1998. Body weight and height were self-reported at recruitment and reassessed
      during follow-up interview in 1999-2004. Percent in weight change was computed
      based on the weight difference over an average of 6 years, and categorized as
      loss >=10 %, loss 5 to <10 %, loss or gain <5 % (stable weight), gain 5 to <10 %,
      and gain >=10 %. Multivariable Cox proportional hazards regression model was
      applied with adjustment for risk factors for hip fracture and body mass index
      (BMI) reported at follow-up interview. RESULTS: About 12 % experienced weight
      loss >=10 %, and another 12 % had weight gain >=10 %. After a mean follow-up of
      9.0 years, we identified 775 incident hip fractures among 42,149 eligible
      participants. Compared to stable weight, weight loss >=10 % was associated with
      39 % increased risk (hazard ratio 1.39; 95 % confidence interval 1.14, 1.69).
      Such elevated risk with weight loss >=10 % was observed in both genders and age
      groups at follow-up (<=65 and >65 years) and in those with baseline BMI >=20
      kg/m(2).There was no significant association with weight gain. CONCLUSIONS: Our
      findings provide evidence that substantial weight loss is an important risk
      factor for osteoporotic hip fractures among the middle-aged to elderly Chinese.

PMID- 25868510
TI  - The position of strontium ranelate in today's management of osteoporosis.
AB  - Osteoporosis accounts for about 3 % of total European health-care spending. The
      low proportion of costs for the pharmacological prevention of osteoporotic
      fracture means that it is highly cost saving, especially in patient with severe
      osteoporosis or patients who cannot take certain osteoporosis medications due to
      issues of contraindications or tolerability. Following recent regulatory changes,
      strontium ranelate is now indicated in patients with severe osteoporosis for whom
      treatment with other osteoporosis treatments is not possible, and without
      contraindications including uncontrolled hypertension, established, current or
      past history of ischaemic heart disease, peripheral arterial disease, and/or
      cerebrovascular disease. We review here today's evidence for the safety and
      efficacy of strontium ranelate. The efficacy of strontium ranelate in patients
      complying with the new prescribing information (i.e. severe osteoporosis without
      contraindications) has been explored in a multivariate analysis of clinical trial
      data, which concluded that the antifracture efficacy of strontium ranelate is
      maintained in patients with severe osteoporosis without contraindications and
      also demonstrated how the new target population mitigates risk. Strontium
      ranelate is therefore an important alternative in today's management of
      osteoporosis, with a positive benefit-risk balance, provided that the revised
      indication and contraindications are followed and cardiovascular risk is
      monitored. The bone community should be reassured that there remain viable
      alternatives in patients in whom treatment with other agents is not possible and
      protection against the debilitating effects of fracture is still feasible in
      patients with severe osteoporosis.

PMID- 25868511
TI  - Serum C3 epimer of 25-hydroxyvitamin D and its determinants in adults: a national
      health examination survey in Thais.
AB  - A high percentage have detectable C3 epimer of 25-hydroxyvitamin D3 (3-epi
      25(OH)D3) in the population of Thai National Health Examination Survey IV.
      INTRODUCTION: C3 epimers of vitamin D have recently been shown to contribute
      significantly to 25-hydroxyvitamin D (25(OH)D) levels in an infant population.
      However, the findings in the general adult population are unclear. Therefore, the
      purpose of the present study is to determine the percentage of the C3 epimer of
      25(OH)D (3-epi-25(OH)D) and its determinants in an adult population. METHODS: A
      subsample of 1148 sera randomly selected from the Thai National Health
      Examination Survey IV (2009) samples were measured for serum 25(OH)D2, 25(OH)D3,
      3-epi-25(OH)D2, and 3-epi-25(OH)D3 by LC-MS/MS method. The relative 3-epimer
      contribution (%) was used to express the amount of 3-epimer-25(OH)D3 as a
      percentage of total 25(OH)D3 (the sum of 25(OH)D3, and 3-epi-25(OH)D3). RESULTS:
      A high proportion of subjects had detectable 3-epi-25(OH)D3 that was <10 % of the
      total 25(OH)D levels. Since the level of total 25(OH)D2 is low, only a minority
      of subjects had detectable 3-epi-25(OH)D2. Multivariate analysis suggested that
      age, male gender, and rural residence were independently related to the 3-epi
      25(OH)D3/total 25(OH)D3 ratio. CONCLUSIONS: A high percentage of Thai adults had
      detectable 3-epi-25(OH)D3 that was <10 % of the total 25(OH)D levels. Age,
      gender, and living in a rural area were associated with the relative amount of 3
      epi-25(OH)D3 to total 25(OH)D3.

PMID- 25868512
TI  - Allocation of the S-genome chromosomes of Aegilops variabilis Eig. carrying
      powdery mildew resistance in triticale (* Triticosecale Wittmack).
AB  - It has been hypothesized that the powdery mildew adult plant resistance (APR)
      controlled by the Pm13 gene in Aegilops longissima Schweinf. & Muschl. (S(l)S(l))
      has been evolutionary transferred to Aegilops variabilis Eig. (UUSS). The
      molecular marker analysis and the visual evaluation of powdery mildew symptoms in
      Ae. variabilis and the Ae. variabilis * Secale cereale amphiploid forms (2n = 6x
      = 42, UUSSRR) showed the presence of product that corresponded to Pm13 marker and
      the lower infection level compared to susceptible model, respectively. This study
      also describes the transfer of Ae. variabilis Eig. (2n = 4x = 28,
      U(v)U(v)S(v)S(v)) chromosomes, carrying powdery mildew resistance, into triticale
      (* Triticosecale Wittm., 2n = 6x = 42, AABBRR) using Ae. variabilis * S. cereale
      amphiploid forms. The individual chromosomes of Ae. variabilis, triticale
      'Lamberto' and hybrids were characterized by genomic and fluorescence in situ
      hybridization (GISH/FISH). The chromosome configurations of obtained hybrid forms
      were studied at first metaphase of meiosis of pollen mother cells (PMCs) using
      GISH. The statistical analysis showed that the way of S-genome chromosome pairing
      and transmission to subsequent hybrid generations was diploid-like and had no
      influence on chromosome pairing of triticale chromosomes. The cytogenetic study
      of hybrid forms were supported by the marker-assisted selection using Pm13 marker
      and visual evaluation of natural infection by Blumeria graminis, that allowed to
      select the addition or substitution lines of hybrids carrying chromosome 3S(v)
      which were tolerant to the powdery mildew infection.

PMID- 25868513
TI  - Diagnostic utility of immunochemical fecal occult blood tests to detect lower
      gastrointestinal lesions in patients with chronic kidney disease.
AB  - PURPOSE: The immunochemical fecal occult blood test (iFOBT) is a useful method to
      screen for lower gastrointestinal (GI) bleeding-related lesions. However, few
      studies have investigated the diagnostic utility of iFOBT in chronic kidney
      disease (CKD). METHODS: We included 691 patients with nondialysis-dependent CKD
      stages 2-5 or those receiving dialysis. Bleeding-related lower GI lesions were
      identified by colonoscopy, and the diagnostic utility of iFOBT was evaluated.
      RESULTS: Bleeding-related lower GI lesions were found in 9.2% of 491 patients
      with CKD stage 2, 17.8% of 107 patients with CKD stage 3/4, and 25.8% of 93
      patients with CKD stage 5/dialysis (p < 0.001). Compared with CKD stage 2, CKD
      stage 5/dialysis was independently associated with a 2.80-fold risk for bleeding
      related lesions (p = 0.019). The iFOBT was positive in 92 (13.3%) patients and
      the area under the receiver operating curve (AUC) for a bleeding-related lesion
      was 0.64 (p < 0.001). The sensitivity of iFOBT increased as the CKD stage
      worsened (20.0 vs 52.6 vs 58.3%; p = 0.002). However, the specificity to detect
      bleeding-related lesions decreased with the severity of CKD stage (94.6 vs. 78.4
      vs. 76.8%; p < 0.001). The AUC of iFOBT to detect adenoma or carcinoma was 0.54
      (p = 0.046), and a similar pattern of sensitivity and specificity was observed
      between different CKD stages. CONCLUSIONS: The prevalence of bleeding-related
      lower GI lesions and the sensitivity of iFOBT to detect these GI lesions
      increased in advanced CKD. However, iFOBT should be used cautiously in these
      patients because its specificity decreased.

PMID- 25868514
TI  - Usefulness of a novel calibrated hood to determine indications for colon
      polypectomy: visual estimation of polyp size is not accurate.
AB  - PURPOSE: Accurate measurement of polyp size during colonoscopy is important
      because the size is a surrogate marker of cancer, but a standardized measurement
      technique to measure polyp size has yet to be determined. We have developed a new
      device "a novel calibrated hood." We assessed polyp size by visual estimation and
      measurement using the calibrated hood. METHODS: Patients who underwent
      polypectomy from November 2012 to September 2013 and who had received screening
      colonoscopy within 6 months prior to the polypectomy were included in this study.
      Polypectomy was performed attaching the calibrated hood. The endoscopist measured
      the polyp size using the calibrated hood. Polyp size was compared between visual
      estimation and measurement using the calibrated hood. RESULTS: Seventy-five
      patients with 157 polyps were included. Seventy-seven polyps fulfilled the
      selection criteria. Mean polyp size by visual estimation was 6.57 +/- 2.15, and
      by using calibrated hood was 5.94 +/- 1.73 (p = 0.005). There was a significant
      difference between measurements using the calibrated hood vs. visual estimation
      by inexperienced trainees; however, there was no difference in case of well
      experienced endoscopists. By visual estimation, 11 of 19 polyps were decided for
      >=5 mm despite being less than 5 mm, and 5 of 58 polyps were decided for <5 mm
      despite being 5 mm or larger in diameter. CONCLUSION: Visual estimation of polyp
      size is not accurate. It is important to measure the size by an objective way,
      and the calibrated hood is useful in measuring polyp size, from the standpoint of
      accurately determining indication for polypectomy.

PMID- 25868515
TI  - A rare case of diffuse pancolonic mantle cell lymphoma.

PMID- 25868516
TI  - Combined identifying granuloma and biopsy culture is useful for diagnosing
      intestinal tuberculosis.
AB  - PURPOSES: Differential diagnosis of intestinal tuberculosis (ITB) and
      inflammatory bowel disease (IBD) can be difficult, but many gastroenterologists
      may only perform biopsy for pathology and their own experience. This study aimed
      to identify optimal sample collection and pathogen detection methods for
      diagnosing ITB. METHODS: A cohort of 182 patients (50 had ITB and 132 had IBD or
      other colonic diseases) who underwent colonoscopy was analyzed. Sensitivity of
      acid-fast bacilli (AFB), culture, polymerase chain reaction (PCR), and granuloma
      pathology on hematoxylin and eosin stain for diagnosing ITB were compared in
      relation to biopsy, endoscopic aspirated intestinal fluid, or standard stool
      evaluations. We also evaluated which combination offered the highest yield to
      diagnose intestinal tuberculosis in addition to granuloma pathology. RESULTS:
      Between ITB and non-ITB, no significant differences were observed in age, sex,
      and nationality. In biopsy analysis, sensitivity was as follows: culture (50%),
      AFB (38%), PCR (25%), granuloma pathology (51%), and caseous granuloma (8.2%),
      while specificity of granuloma pathology was low (80%), compared to other tests.
      In intestinal fluid analysis, sensitivity was as follows: culture (46%), AFB
      (42%), and PCR (35%). In standard stool analysis, sensitivity was as follows:
      culture (47%), AFB (37%), and PCR (23%). Granuloma pathology plus biopsy culture
      offered the highest combination sensitivity (77 %), significantly (P < 0.01)
      higher than that for granuloma pathology alone (51%). CONCLUSIONS: When
      encountering suspected intestinal tuberculosis or IBD on colonoscopy, biopsy
      culture is recommended in addition to pathological assessment of granuloma. This
      diagnostic strategy will lead to accurate differential diagnosis of colonic
      disease, facilitating appropriate treatment.

PMID- 25868517
TI  - Long-term effects of a regional care pathway for patients with rectal cancer.
AB  - PURPOSE: Introducing care pathways is seen as a method to realise patient
      focussed care conform evidence-based guidelines. The goal of this study is to
      determine the long-term effects of a regional care pathway for patients with
      rectal cancer. PATIENTS AND METHODS: Data on almost 400 patients with rectal
      carcinoma from three hospitals were obtained from the Netherlands Cancer Registry
      and the Dutch Surgical Colorectal Audit. Results on seven structure and process
      indicators were analysed and compared before and at two time points after
      implementing a regional care pathway over a total period from 2007 to 2012. To
      determine motivation and interpret the results, relevant professionals of the
      participating hospitals were interviewed. RESULTS: After implementing the care
      pathway, the performance of computed tomography (CT) scans in the diagnostic
      phase significantly improved (p = 0.007/0.07). The number of patients discussed
      in the preoperative multidisciplinary team (MDT) meeting improved significantly
      (p = <0.001), and after implementing the care pathway, 94% of the patients were
      discussed. Further, a significant reduction in time between the first tumour
      biopsy and the MDT meeting was realised (p = 0.01). Professionals stated that the
      regional care pathway has led to more clarity about the patient route and more
      awareness about complying with evidence-based guidelines. CONCLUSIONS: The
      regional care pathway provided a solid basis for uniforming care, working
      according evidence-based guidelines and further cooperation on regional level.
      For mainly the waiting and throughput times, the guidelines and norms had
      probably a stronger effect on the results than the care pathway.

PMID- 25868518
TI  - Early CT perfusion changes and blood-brain barrier permeability after aneurysmal
      subarachnoid hemorrhage.
AB  - INTRODUCTION: Early brain injury (EBI) can occur within 72 h of aneurysmal
      subarachnoid hemorrhage (aSAH). The objective of this study was to determine if
      there are differences in early CTP parameters (<72 h) with respect to delayed
      cerebral ischemia (DCI), cerebral infarction, and functional outcome. METHODS: We
      performed a prospective cohort study of aSAH patients admitted to a single
      tertiary care center. MTT, CBF and blood-brain barrier permeability (PS) were
      quantified with CTP within 72 h of aneurysm rupture. Primary outcomes were
      functional outcome by the Modified Rankin Scale (mRS) at 3 months and cerebral
      infarction. Secondary outcome was the development of DCI. Differences between
      early CTP parameters were determined with respect to primary and secondary
      outcomes. RESULTS: Fifty aSAH patients were included in the final analysis. MTT
      was significantly higher in patients who developed DCI (6.7 +/- 1.2 vs 5.9 +/-
      1.0; p = 0.03) and cerebral infarction (7.0 +/- 1.2 vs 5.9 +/- 0.9; p = 0.007);
      however, no difference in MTT was found between patients with and without a poor
      outcome (mRS > 2). Early CBF and PS did not differ with respect to functional
      outcome, DCI, and cerebral infarction. CONCLUSIONS: Elevated MTT within 72 h of
      aneurysm rupture is associated with DCI and cerebral infarction but not with long
      term functional outcome. Blood-brain barrier permeability, as assessed by CT
      perfusion, was not associated with DCI or worse outcome in this cohort.

PMID- 25868520
TI  - Lung cancer surgery in patients aged 80 years or older: an analysis of risk
      factors, morbidity, and mortality.
AB  - INTRODUCTION: As the population ages, the age of patients undergoing thoracic
      surgery increases, and elderly patients often have more comorbidities than
      younger patients. METHODS: This retrospective study observed preoperative
      comorbidities, surgical procedures and postoperative morbidity and mortality
      after lung cancer surgery in patients 80 years of age or older. The medical
      records of lung cancer patients 80 years of age or older who underwent surgery
      from January 2003 to December 2012 were reviewed. RESULTS: There were 49 patients
      (27 males, 22 females), with a median age of 83 years. Thirty patients underwent
      major pulmonary resection and 18 patients underwent limited pulmonary resection.
      The median Charlson comorbidity index was 3. Although approximately two-thirds of
      the patients (20 patients; 40.8%) experienced some kind of postoperative
      morbidity, more than 80% of the complications were grade 1 or 2 according to the
      Clavien-Dindo classification. Cerebrovascular disease and chronic obstructive
      pulmonary disease were significantly associated with moderate-to-severe
      complications. Postoperative death was observed in two cases (4.1%). In addition,
      an increased American Society of Anesthesiologists classification score and past
      history of myocardial infarction, congestive heart failure and/or diabetes
      mellitus with end-organ damage were significantly associated with mortality. The
      overall survival rate was 79.6% at 3 years and 53.1% at 5 years. CONCLUSIONS:
      Thoracic surgery shows acceptable morbidity and mortality in patients 80 years of
      age or older. Patients 80 years of age or older should be offered the best
      treatments, including surgery, with careful patient evaluation and selection.

PMID- 25868521
TI  - Differential response of terpenes and anthraquinones derivatives in Rumex
      dentatus and Lavandula officinalis to harsh winters across north-western
      Himalaya.
AB  - Herbs adapted to diverse climates exhibit distinct variability to fluctuating
      temperatures and demonstrate various metabolic and physiological adaptations to
      harsh environments. In this research, Rumex dentatus L. and Lavandula officinalis
      L. were collected before snowfall in September-November to evaluate variability
      in major phytoconstituents to diverse seasonal regime. LC-MS was used for
      simultaneous determination of eight anthraquinone derivatives in R. dentatus,
      i.e. emodin, physcion, chrysophanol, physcion glucoside, endocrocin, emodin
      glucoside, chrysophanol glucoside and chromone derivatives and monoterpenes in L.
      officinalis i.e. (Z)-beta-ocimene, (E)-beta-ocimene, terpene alcohol, terpin-4
      ol, acetate ester-linalyl acetate and bicyclic sesquiterpene (E)-caryophyllene.
      The correlation analysis confirmed significant variation in anthraquinone
      glucoside and terpene content within Rumex and Lavender, respectively, and
      altitude was established as the determinant factor in secondary metabolism of
      both herbs. The study concludes the propagation of herbs in bioclimatic belts
      which favour accumulation of major constituents and validate their greater
      pharmacological activity. 

PMID- 25868519
TI  - The prion hypothesis of Parkinson's disease.
AB  - The discovery of alpha-synuclein's prion-like behaviors in mammals, as well as a
      non-Mendelian type of inheritance, has led to a new concept in biology, the
      "prion hypothesis" of Parkinson's disease. The misfolding and aggregation of
      alpha-synuclein (alpha-syn) within the nervous system occur in many
      neurodegenerative diseases including Parkinson's disease (PD), Lewy body dementia
      (LBD), and multiple system atrophy (MSA). The molecular basis of
      synucleinopathies appears to be tightly coupled to alpha-syn's conformational
      conversion and fibril formation. The pathological form of alpha-syn consists of
      oligomers and fibrils with rich in beta-sheets. The conversion of its alpha
      helical structure to the beta-sheet rich fibril is a defining pathologic feature
      of alpha-syn. These kinds of disorders have been classified as protein misfolding
      diseases or proteopathies which share key biophysical and biochemical
      characteristics with prion diseases. In this review, we highlight alpha-syn's
      prion-like activities in PD and PD models, describe the idea of a prion-like
      mechanism contributing to PD pathology, and discuss several key molecules that
      can modulate the alpha-syn accumulation and propagation. 

PMID- 25868522
TI  - microRNAs and oligometastasis.

PMID- 25868523
TI  - Neurogenic bladder and neuroendocrine abnormalities in Pol III-related
      leukodystrophy.
AB  - BACKGROUND: Pol III-related leukodystrophies, including 4H leukodystrophy, are
      recently recognized disorders that comprise hypomyelination and various
      neurologic and non-neurologic clinical manifestations. We report the unique
      neurologic presentation of the micturition dysfunction in Pol III-related
      leukodystrophy and describe the novel endocrine abnormalities in this entity.
      CASE PRESENTATION: A 32-year-old Caucasian female exhibited chronic urinary
      incontinence that commenced at the age of 7 years and remained the unexplained
      symptom more than two decades before the onset of progressive neurologic decline.
      A transient growth failure and absent sexual development with hypoprolactinemia
      appeared in the meanwhile. Neurologic, endocrine, neuroradiologic, and genetic
      evaluation performed only in the patient's thirties, confirmed the diagnosis of
      4H leukodystrophy as the only cause of the micturition disturbance. CONCLUSION:
      The report shows for the first time that an unexplained chronic bladder
      dysfunction should be evaluated also as a possible 4H leukodystrophy, thus
      alerting to the unexpected neurologic and endocrine features in 4H
      leukodystrophy.

PMID- 25868524
TI  - Mitochondrial genome of the Emberiza jankowskii (Emberizidae: Emberiza).
AB  - Emberiza jankowskii is an Endangered species, whose population quantity decreased
      year by year in the limited distribution areas. The complete mitochondrial genome
      of E. jankowskii (16,776 bp in length) consists of 37 genes (13 protein-coding
      genes, 2 rRNA genes, and 22 tRNA genes) and a non-coding region (D-loop), which
      is similar to the typical mtDNA of vertebrates. All the protein-coding genes in
      E. jankowskii are distributed on the H-strand, except the ND6 subunit gene and
      ten tRNA genes, which are encoded on the L-strand. A preliminary phylogenetic
      analysis has been carried out with eight bunting species and other related
      species.

PMID- 25868525
TI  - The complete mitochondrial genome of the American crow, Corvus brachyrhynchos
      (Passeriformes, Corvidae).
AB  - The American crow, Corvus brachyrhynchos (Passeriformes, Corvidae), is a large
      passerine bird species closely related to the raven. Herein, we first published
      the complete mitochondrial genome of American crows. The mitogenome was 16,917 bp
      long, and composed of 13 protein-coding genes, 22 tRNA genes, two rRNA genes, and
      one putative control region. Most protein-coding genes started with a traditional
      ATG codon except for COI, which initiated with an infrequent start codon GTG
      instead, and terminated with the mitochondria stop codon (TAA/AGG/AGA) or a
      single T base. The mitogenome structural organization is identical to that of the
      other corvus species and related genera. The overall GC content is 44.25% which
      is lower than AT. Using the 12 protein-coding genes of Corvus brachyrhynchos in
      this study, together with 10 other closely species, we constructed the species
      phylogenetic tree to verify the accuracy and utility of new determined mitogenome
      sequences. We expect that using the full mitogenome to address taxonomic issues
      and study the related evolution events. Moreover, this is the first report of
      bird mitogenomes after 48 avian species genome project achievements released in
      December 2014.

PMID- 25868526
TI  - The influence of active site conformations on the hydride transfer step of the
      thymidylate synthase reaction mechanism.
AB  - The hydride transfer from C6 of tetrahydrofolate to the reaction's exocyclic
      methylene-dUMP intermediate is the rate limiting step in thymidylate synthase
      (TSase) catalysis. This step has been studied by means of QM/MM molecular
      dynamics simulations to generate the corresponding free energy surfaces. The use
      of two different initial X-ray structures has allowed exploring different
      conformational spaces and the existence of chemical paths with not only different
      reactivities but also different reaction mechanisms. The results confirm that
      this chemical conversion takes place preferentially via a concerted mechanism
      where the hydride transfer is conjugated to thiol-elimination from the product.
      The findings also confirm the labile character of the substrate-enzyme covalent
      bond established between the C6 of the nucleotide substrate and a conserved
      cysteine residue. The calculations also reproduce and rationalize a normal H/T 2
      degrees  kinetic isotope effect measured for that step. From a computational
      point of view, the results demonstrate that the use of an incomplete number of
      coordinates to describe the real reaction coordinate can render biased results. 

PMID- 25868528
TI  - Mean reticulocyte volume: a specific parameter to screen for hereditary
      spherocytosis.
AB  - This study assessed the value of mean reticulocyte volume (MRV) for differential
      diagnosis of hereditary spherocytosis (HS) so as to develop conventional and new
      specific screen indexes. Subjects in this study were divided into three groups:
      53 cases in HS group, 217 cases in hemolytic anemia control group (109 cases of
      thalassemia (THAL), 56 cases of glucose-6-phosphate dehydrogenase G6PD deficiency
      anemia, and 52 cases of autoimmune hemolytic anemia (AIHA)), and 100 cases in
      healthy control group. We analyzed erythrocyte and reticulocyte parameters
      including MRV, mean sphered corpuscular volume, mean corpuscular hemoglobin
      concentration, and immature reticulocyte fraction. Results demonstrated that MRV
      was significantly lower in the HS group but significantly higher in the AIHA and
      G6PD deficiency anemia groups than that in the healthy control group (P = 0.000).
      MRV was not significantly different between the AIHA and G6PD deficiency anemia
      groups (P = 0.977) and between the healthy control and THAL groups (P = 0.168).
      The area under the ROC curve of MRV for diagnosis of HS was 0.942, with a
      standard error of 0.019, 95% confidence interval of 0.905-0.979, and optimal
      critical diagnosis point of 95.77 fL. When the MRV was <=95.77 fL, the
      sensitivity and specificity for diagnosis of HS were 86.80% and 91.20%,
      respectively. Therefore, MRV is a general and specific new index for screening HS
      and important for differential diagnosis of different types of hemolytic anemia. 

PMID- 25868529
TI  - Are Economic Development and Education Improvement Associated with Participation
      in Transnational Terrorism?
AB  - Using transnational terrorism data from 1980 to 2000, this study empirically
      examines the relationships between frequency of participation in transnational
      terrorism acts and economic development and education improvement. We find an
      inverse U-shaped association between the frequency of various nationals acting as
      perpetrators in transnational terrorism acts and per capita income in their
      respective home countries. As per capita incomes increase from relatively low
      levels, frequencies of participation in transnational terrorism increase.
      However, at sufficiently higher levels of per capita income, further increase in
      per capita income is negatively associated with the rate of participation in
      transnational terrorism. Education improvement from elementary to secondary is
      positively correlated with frequency of participation in transnational terrorism
      events, whereas further improvement from secondary to tertiary level is
      negatively correlated with participation in transnational terrorism. We also find
      that citizens of countries with greater openness to international trade, lower
      degree of income inequality, greater economic freedom, larger proportion of
      population with tertiary education, and less religious prevalence participate in
      transnational terrorism events less frequently. 

PMID- 25868531
TI  - Intranasal administration with recombinant Lactococcus lactis expressing heme
      oxygenase-1 reduces hyperoxia-induced lung inflammation in rat pups.
AB  - OBJECTIVES: To evaluate the effects of a recombinant strain of Lactococcus lactis
      secreting bioactive heme oxygenase-1 (LL-HO-1) in a model of hyperoxia-induced
      lung injury in rat pups RESULTS: Intranasal administration with LL-HO-1
      significantly reduced hyperoxia-induced lung injury as demonstrated by a
      decreased wet/dry ratio, myeloperoxidase activity in lung tissue, tumor necrosis
      factor alpha levels in bronchoalveolar lavage (BAL) fluid, and attenuated lung
      injury scores. Although expression of HO-1 and NADPH oxidase-1 and production of
      superoxide in lung tissue were not affected by LL-HO-1 treatment, HO-1 levels in
      nasal mucosa and interleukin-10 concentrations in BAL fluid significantly
      increased compared with the hyperoxia control group CONCLUSIONS: Intranasal
      administration of LL-HO-1 protects against hyperoxia-induced lung damage,
      apparently through attenuation of inflammation.

PMID- 25868532
TI  - Quantitative analysis of cellular proteome alterations of Pseudomonas putida to
      naphthalene-induced stress.
AB  - OBJECTIVE: To investigate whether genes other than the operons nahAaAbAcAdBFCED
      and nahGTHINLOMKJ of Pseudomonas putida are involved in the tolerance of the
      bacterium to naphthalene. RESULTS: Cellular responses of P. putida ND6 grown with
      2 and 4 g naphthalene/l were investigated using a quantitative proteomic-based
      approach. Comparative analysis of the proteome data identified that the
      expression levels of 22 proteins involved in heat shock and universal stress
      response, naphthalene degradation, cell envelope synthesis, and motility were up
      regulated; while the expression levels of 26 proteins involved in protein and
      fatty acid synthesis, carbon compound, nucleotide, and amino acid metabolism, and
      small molecule transport were down-regulated. CONCLUSION: Our findings offer
      insights into the cellular response of P. putida to high naphthalene
      concentrations at the protein level.

PMID- 25868533
TI  - Insect life history and the evolution of bacterial mutualism.
AB  - Bacterial symbiosis has played a fundamental role in the evolution of eukaryotes.
      However, we still know little about how cooperative relationships with bacteria
      originate, and why they form in some host species but not others. Facultative
      symbionts that are beneficial, but not essential, provide unique insights into
      these processes. We use data from over a hundred aphid species to test if host
      life history is associated with the presence of facultative symbionts. We find
      that aphid species that have mutualistic associations with ants that protect them
      from natural enemies are less likely to carry symbionts that provide similar
      benefits. We also find one symbiont species occurs more frequently in unrelated
      aphid species that specialise on certain plant genera. In addition, aphid species
      that attack multiple plants often carry different symbiont complements. Our
      findings provide evidence of the ecological conditions that facilitate stable,
      mutually beneficial relationships between microbes and eukaryotic hosts. 

PMID- 25868535
TI  - Obama supports ban on therapy to change sexual orientation of youth.

PMID- 25868534
TI  - Replication study of the milwaukee inventory for subtypes of trichotillomania
      adult version in a clinically characterized sample.
AB  - In the present study, we evaluated the Milwaukee Inventory for Subtypes of
      Trichotillomania-Adult Version (MIST-A) in a replication sample of clinically
      characterized hair pullers using exploratory factor analysis (EFA; N = 193). EFA
      eigenvalues and visual inspection of our scree plot revealed a two-factor
      solution. Factor structure coefficients and internal consistencies suggested a 13
      item scale with an 8-item "Intention" scale and a 5-item "Emotion" scale. Both
      scales displayed good construct and discriminant validity. These findings
      indicate the need for a revised scale that provides a more refined assessment of
      pulling phenomenology that can facilitate future treatment advances. 

PMID- 25868536
TI  - Repeatability and Minimal Detectable Change in Longitudinal Median Nerve
      Excursion Measures During Upper Limb Neurodynamic Techniques in a Mixed
      Population: A Pilot Study Using Musculoskeletal Ultrasound Imaging.
AB  - This study determined test-retest reliability and minimum detectable change in
      longitudinal median nerve excursion during upper limb neurodynamic tests (ULNTs).
      Seven participants with unilateral or bilateral carpal tunnel syndrome and 11
      healthy participants were randomly tested with two ULNTs (i.e., tensioner and
      slider). Each ULNT was performed three times each at 45 degrees  and 90 degrees 
      of shoulder abduction on two separate visits. Video sequences of median nerve
      excursion, recorded by a physical therapist using ultrasound imaging, were
      quantified using computer software. The generalizability theory, encompassing a G
      Study and a D-study, measured the dependability coefficient (Phi) along with
      standard error of measurement (SEM) accuracy and allowed various testing
      protocols to be proposed. The highest reliability (Phi = 0.84) and lowest minimal
      measurement error (SEM = 0.58 mm) of the longitudinal median nerve excursion were
      reached during the ULNT-slider performed with 45 degrees  of shoulder abduction
      and when measures obtained from three different image sequences recorded during a
      single visit were averaged. It is recommended that longitudinal median nerve
      excursion measures computed from three separate image sequences recorded during a
      single visit be averaged in clinical practice. Ideally, adding a second visit
      (six image sequences) is also suggested in research protocols. 

PMID- 25868537
TI  - The rise of marijuana and the fall of cocaine in the United States: for better,
      for worse?

PMID- 25868538
TI  - We know too little about demand: comments on 'cocaine's fall'.

PMID- 25868539
TI  - Drug use data, drug use theories and drug use policies in the United States: a
      combinatorial lack of connections.

PMID- 25868540
TI  - A socio-cultural view of trends in drug use indicators.

PMID- 25868541
TI  - On a search for useful indicators... or not?

PMID- 25868542
TI  - Beyond prevalence: importance of estimating drug consumption and expenditures.

PMID- 25868543
TI  - Commentary on Zhou et al. (2015): Research on methadone maintenance treatment
      (MMT) as prevention for HCV infection--MMT is not a single variable.

PMID- 25868544
TI  - Commentary on Cunningham et al. (2015): Essential chemical controls--miracle from
      a black box?

PMID- 25868545
TI  - Commentary on Valdivieso Lopez et al. (2015): Lessons to be learnt from a
      randomized controlled trial of smoking prevention in secondary schools.

PMID- 25868546
TI  - News and notes: compiled by john witton and jean 'reilly.

PMID- 25868549
TI  - Effects of message framing and visual-fear appeals on smoker responses to
      antismoking ads.
AB  - This study examined the effects of antismoking ads on Korean adult male smokers.
      An experiment was conducted to explore how message framing and visual-fear
      appeals embedded in antismoking ads may influence ad-evoked fear, threat
      appraisals, and intention to quit smoking. Results showed that (a) antismoking ad
      exposure increased ad-evoked fear and cessation intention; (b) optimistic bias
      was stronger when the visual-fear appeal was absent in antismoking ads; and 

PMID- 25868548
TI  - The C. elegans dauer larva as a paradigm to study metabolic suppression and
      desiccation tolerance.
AB  - MAIN CONCLUSION: The hypometabolic, stress-resistant dauer larva of
      Caenorhabditis elegans serves as an excellent model to study the molecular
      mechanisms of desiccation tolerance, such as maintenance of membrane
      organization, protein folding, xenobiotic and ROS detoxification in the dry
      state. Many organisms from diverse taxa of life have the remarkable ability to
      survive extreme desiccation in the nature by entering an ametabolic state known
      as anhydrobiosis (life without water). The hallmark of the anhydrobiotic state is
      the achievement and maintenance of an exceedingly low metabolic rate, as well as
      preservation of the structural integrity of the cell. Although described more
      than three centuries ago, the biochemical and biophysical mechanisms underlying
      this phenomenon are still not fully comprehended. This is mainly due to the fact
      that anhydrobiosis in animals was studied using non-model organisms, which are
      very difficult, if not impossible, to manipulate at the molecular level.
      Recently, we introduced the roundworm (nematode) Caenorhabditis elegans as a
      model for anhydrobiosis. Taking advantage of powerful genetic, biochemical and
      biophysical tools, we investigated several aspects of anhydrobiosis in a
      particular developmental stage (the dauer larva) of this organism. First, our
      studies allowed confirming the previously suggested role of the disaccharide
      trehalose in the preservation of lipid membranes. Moreover, in addition to known
      pathways such as reactive oxygen species defense, heat-shock and intrinsically
      disordered protein expression, evidence for some novel strategies of
      anhydrobiosis has been obtained. These are increased glyoxalase activity,
      polyamine and polyunsaturated fatty acid biosynthesis. All these pathways may
      constitute a generic toolbox of anhydrobiosis, which is possibly conserved
      between animals and plants.

PMID- 25868550
TI  - Self-harm history predicts resistance to inpatient treatment of body shape
      aversion in women with eating disorders: The role of negative affect.
AB  - Although self-harm has been observed among patients with eating disorders, the
      effects of such tendencies on treatment outcomes are unclear. The current study
      employed structural equation modeling to (a) evaluate the relationship between
      self-harm and changes in body dissatisfaction and drive for thinness in a large
      sample of patients (n = 2061) who underwent inpatient treatment, and (b) to
      examine whether the relationship between self-harm and changes in body
      dissatisfaction and drive for thinness during inpatient treatment remains
      significant when controlling for change in negative affect during treatment.
      Results revealed that patients with a history of self-harm reported significantly
      less reduction in body dissatisfaction and drive for thinness following
      treatment. Patients experiencing less change in negative affect also reported
      significantly less reduction in body dissatisfaction and drive for thinness after
      discharge from treatment. However, the association between history of self-harm
      and reduction in body dissatisfaction and drive for thinness after treatment
      became non-significant when controlling for change in negative affect. This
      pattern of findings was also replicated among patients with a primary diagnosis
      of anorexia nervosa (n = 845), bulimia nervosa (n = 565), and eating disorder not
      otherwise specified (n = 651). The implications of these findings for delineating
      the specific role of self-harm in the nature and treatment of eating disorders
      are discussed. 

PMID- 25868551
TI  - Controlling Time-Dependent Confounding by Health Status and Frailty: Restriction
      Versus Statistical Adjustment.
AB  - Nonexperimental studies of preventive interventions are often biased because of
      the healthy-user effect and, in frail populations, because of confounding by
      functional status. Bias is evident when estimating influenza vaccine
      effectiveness, even after adjustment for claims-based indicators of illness. We
      explored bias reduction methods while estimating vaccine effectiveness in a
      cohort of adult hemodialysis patients. Using the United States Renal Data System
      and linked data from a commercial dialysis provider, we estimated vaccine
      effectiveness using a Cox proportional hazards marginal structural model of all
      cause mortality before and during 3 influenza seasons in 2005/2006 through
      2007/2008. To improve confounding control, we added frailty indicators to the
      model, measured time-varying confounders at different time intervals, and
      restricted the sample in multiple ways. Crude and baseline-adjusted marginal
      structural models remained strongly biased. Restricting to a healthier population
      removed some unmeasured confounding; however, this reduced the sample size,
      resulting in wide confidence intervals. We estimated an influenza vaccine
      effectiveness of 9% (hazard ratio = 0.91, 95% confidence interval: 0.72, 1.15)
      when bias was minimized through cohort restriction. In this study, the healthy
      user bias could not be controlled through statistical adjustment; however, sample
      restriction reduced much of the bias. 

PMID- 25868552
TI  - Health literacy and parent attitudes about weight control for children.
AB  - The purpose of this study was to examine associations between parental health
      literacy and parent attitudes about weight control strategies for young children.
      Parental low health literacy has been associated with poor child health outcomes,
      yet little is known about its relationship to child weight control and weight
      related health information-seeking preferences. Data were drawn from the STRONG
      Kids Study, a Midwest panel survey among parents of preschool aged children (n =
      497). Parents endorsed an average of 4.3 (SD =2.8) weight loss strategies, 53%
      endorsed all three recommended weight loss strategies for children, and fewer
      than 1% of parents endorsed any unsafe strategies. Parents were most likely to
      seek child weight loss information from healthcare professionals but those with
      low (vs. adequate) health literacy were significantly less likely to use the
      Internet or books and more likely to use minister/clergy as sources. Poisson and
      logistic regressions showed that higher health literacy was associated with
      endorsement of more strategies overall, more recommended strategies, and greater
      odds of endorsing each specific recommended strategy for child weight control,
      after adjusting for parent age, education, race/ethnicity, income, marital
      status, weight concern, and child BMI percentile. Findings suggest that health
      literacy impacts parental views about child weight loss strategies and health
      information-seeking preferences. Pediatric weight loss advice to parents should
      include assessment of parent attitudes and prior knowledge about child weight
      control and facilitate parent access to reliable sources of evidence-informed
      child weight control information. 

PMID- 25868553
TI  - Maxillofacial gunshot wounds.
AB  - The majority of maxillofacial gunshot wounds are caused by suicide attempts.
      Young men are affected most often. When the lower one-third of the face is
      involved, airway patency (1.6% of the cases) and hemorrhage control (1.9% of the
      cases) are the two most urgent complications to monitor and prevent. Spinal
      fractures are observed with 10% of maxillary injuries and in 20% of orbital
      injuries. Actions to treat the facial gunshot victim need to be performed,
      keeping in mind spine immobilization until radiographic imaging is complete and
      any required spinal stabilization accomplished. Patients should be transported to
      a trauma center equipped to deal with maxillofacial and neurosurgery because 40%
      require emergency surgery. The mortality rate of maxillofacial injuries shortly
      after arrival at a hospital varies from 2.8% to 11.0%. Complications such as
      hemiparesis or cranial nerve paralysis occur in 20% of survivors. This case has
      been reported on a victim of four gunshot injuries. One of the gunshots was to
      the left mandibular ramus and became lodged in the C4 vertebral bone.

PMID- 25868555
TI  - Analysis of Urinary Biomarkers for Smoking Crack Cocaine: Results of a Danish
      Laboratory Study.
AB  - Crack cocaine (free-base cocaine) smokers belong to a subgroup of marginalized
      drug users exposed to severe health risks and great social harm. Detection of the
      urinary, pyrolytic biomarker methylecgonidine (MED) and its metabolite ecgonidine
      (ED) secures an unambiguous confirmation of crack cocaine smoking. Although
      prevalence studies of cocaine based upon self-reporting may not be accurate,
      laboratory analysis is seldom used for neither diagnostic purpose nor early
      identification of crack cocaine smoking, which is far more severe than snorting
      cocaine. A new analytical method was validated for MED, ED and other relevant
      cocaine metabolites using automated liquid handling and column switching coupled
      to liquid chromatography and tandem mass spectrometry. Limit of quantification
      was 30 ng/mL for ED and MED. This method was applied in a laboratory study of
      urine samples (n = 110) from cocaine users in Denmark subjected to routine drugs
      of-abuse testing. Crack cocaine smoking was confirmed by the presence of MED
      and/or ED. Eighty-four samples (76.4%) were found positive for crack cocaine
      smoking in this group of problematic cocaine users. MED was only detected in 5.9%
      of the positive samples. The study shows a prevalence 3-fold higher to that
      recently suggested by European Monitoring Centre for Drugs and Drug Addiction. We
      therefore advocate that the urinary biomarkers MED and ED are included in routine
      testing methods for clinical toxicology. This may lead to an earlier
      identification of crack cocaine smoking and possibly prevent a more severe drug
      use. 

PMID- 25868556
TI  - Optimization and Validation of an ETAAS Method for the Determination of Nickel in
      Postmortem Material.
AB  - In this article, optimization and validation of a procedure for the determination
      of total nickel in wet digested samples of human body tissues (internal organs)
      for forensic toxicological purposes are presented. Four experimental setups of
      the electrothermal atomic absorption spectrometry (ETAAS) using a Solaar MQZe
      (Thermo Electron Co.) were compared, using the following (i) no modifier, (ii)
      magnesium nitrate, (iii) palladium nitrate and (iv) magnesium nitrate and
      ammonium dihydrogen phosphate mixture as chemical modifiers. It was ascertained
      that the ETAAS without any modifier with 1,300/2,400 degrees C as the pyrolysis
      and atomization temperatures, respectively, can be used to determine total nickel
      at reference levels in biological materials as well as its levels found in
      chronic or acute poisonings. The method developed was validated, obtaining a
      linear range of calibration from 0.76 to 15.0 MUg/L, limit of detection at 0.23
      ug/L, limit of quantification at 0.76 ug/L, precision (as relative standard
      deviation) up to 10% and accuracy of 97.1% for the analysis of certified material
      (SRM 1577c Bovine Liver) and within a range from 99.2 to 109.9% for the recovery
      of fortified liver samples. 

PMID- 25868554
TI  - Sphaeropsidin A shows promising activity against drug-resistant cancer cells by
      targeting regulatory volume increase.
AB  - Despite the recent advances in the treatment of tumors with intrinsic
      chemotherapy resistance, such as melanoma and renal cancers, their prognosis
      remains poor and new chemical agents with promising activity against these
      cancers are urgently needed. Sphaeropsidin A, a fungal metabolite whose
      anticancer potential had previously received little attention, was isolated from
      Diplodia cupressi and found to display specific anticancer activity in vitro
      against melanoma and kidney cancer subpanels in the National Cancer Institute
      (NCI) 60-cell line screen. The NCI data revealed a mean LC50 of ca. 10 uM and a
      cellular sensitivity profile that did not match that of any other agent in the
      765,000 compound database. Subsequent mechanistic studies in melanoma and other
      multidrug-resistant in vitro cancer models showed that sphaeropsidin A can
      overcome apoptosis as well as multidrug resistance by inducing a marked and rapid
      cellular shrinkage related to the loss of intracellular Cl(-) and the decreased
      HCO3 (-) concentration in the culture supernatant. These changes in ion
      homeostasis and the absence of effects on the plasma membrane potential were
      attributed to the sphaeropsidin A-induced impairment of regulatory volume
      increase (RVI). Preliminary results also indicate that depending on the type of
      cancer, the sphaeropsidin A effects on RVI could be related to Na-K-2Cl
      electroneutral cotransporter or Cl(-)/HCO3 (-) anion exchanger(s) targeting. This
      study underscores the modulation of ion-transporter activity as a promising
      therapeutic strategy to combat drug-resistant cancers and identifies the fungal
      metabolite, sphaeropsidin A, as a lead to develop anticancer agents targeting RVI
      in cancer cells. 

PMID- 25868557
TI  - Azole antifungal inhibition of buprenorphine, methadone and oxycodone in vitro
      metabolism.
AB  - Opioid-related mortality rates have escalated. Drug interactions may increase
      blood concentrations of the opioid. We therefore used human liver microsomes
      (HLMs) and cDNA-expressed human cytochrome P450s (rCYPs) to study in vitro
      inhibition of buprenorphine metabolism to norbuprenorphine (CYP3A4 and 2C8),
      oxycodone metabolism to noroxycodone (CYP3A4 and 2C18) and oxymorphone (CYP2D6),
      and methadone metabolism to R- and S-2-ethylidene-1,5-dimethyl-3,3
      diphenylpyrrolidine (EDDP; CYP3A4 and 2B6). In this study, we have examined the
      inhibitory effect of 12 (mostly antifungal) azoles. These compounds have a wide
      range of solubility; to keep organic solvent <=1%, there was an equally wide
      range of highest concentration tested (e.g., itraconazole 5 uM to fluconazole
      1000 uM). Inhibitors were first incubated with HLMs at three concentrations with
      or without preincubation of inhibitor with reducing equivalents to also screen
      for time-dependent inhibition (TDI). Posaconazole displayed evidence of TDI;
      metronidazole and albendazole had no significant effect. Azoles were next
      screened at the highest achievable concentration for non-CYP3A4 pathways. IC50
      values (uM) were determined for most CYP3A4 pathways (ranges) and other pathways
      as dictated by screen results: clotrimazole (0.30 - 0.35; others >30 uM);
      econazole (2.2 - 4.9; 2B6 R-EDDP - 9.5, S-EDDP - 6.8; 2C8 - 6.0; 2C18 - 1.0; 2D6 
      1.2); fluconazole (7.7 - 66; 2B6 - 313, 361; 2C8 - 1240; 2C18 - 17; 2D6 - 1000);
      itraconazole (2.5 to >5; others >5); ketoconazole (0.032 - 0.094; 2B6 - 12, 31;
      2C8 - 78; 2C18 - 0.98; 2D6 - 182); miconazole (2.3 - 7.6; 2B6 - 2.8, 2.8; 2C8 -
      5.3; 2C18 - 3.1; 2D6 - 5.9); posaconazole (3.4 - 20; 2C18 - 3.8; others >30);
      terconazole (0.48 to >10; 2C18 - 8.1; others >10) and voriconazole (0.40 - 15;
      2B6 - 2.4, 2.5; 2C8 - 170; 2C18 - 13; 2D6 >300). Modeling based on estimated Ki
      values and plasma concentrations from the literature suggest that the orally
      administered azoles, particularly ketoconazole and voriconazole, have the
      greatest potential for inhibiting CYP3A4 pathways, as does voriconazole for the
      CYP2B6 pathways. Azoles used for mucosal and topical applications did not exceed
      the modeling threshold. 

PMID- 25868559
TI  - Prostate cancer: The complex relationships of malignant cells in lethal
      metastatic castration-resistant disease.

PMID- 25868558
TI  - Landmarks in erectile function recovery after radical prostatectomy.
AB  - The description of the nerve-sparing technique of radical prostatectomy by Walsh
      was one of the major breakthroughs in the surgical treatment of prostate cancer
      in the 20(th) century. However, despite this advance and consequent technological
      refinements to nerve-sparing surgery, a large proportion of men still suffer from
      erectile dysfunction (ED) as a complication of prostatectomy. A plethora of
      therapeutic approaches have been proposed to optimize erectile function recovery
      in these patients. Several preclinical and translational studies have shown
      benefits of therapies including PDE5 inhibitor (PDE5I) treatment,
      immunomodulation, neurotrophic factor administration, and regenerative
      techniques, such as stem cell therapy, in animal models. However, most of these
      approaches have either failed to translate to clinical use or have yet to be
      studied in human subjects. Penile rehabilitation with PDE5Is is currently the
      most commonly used clinical strategy, in spite of the absence of solid clinical
      evidence to support its use. 

PMID- 25868560
TI  - Transplantation: APOL1 gene variants associated with renal allograft failure.

PMID- 25868561
TI  - Prostate cancer: Sequencing AR-targeted agents might be ineffective in mCRPC.

PMID- 25868562
TI  - Urinary incontinence: Brain reaction to bladder filling predicts response to
      pelvic floor muscle training.

PMID- 25868563
TI  - What is the stone-free rate following flexible ureteroscopy for kidney stones?
AB  - Flexible ureteroscopy (URS) is increasingly being used as the first-line
      treatment for patients with renal stones. Despite this increase in use,
      substantial variations exist in the reported stone-free rates (SFR) following
      flexible URS. These variations are a result of inconsistencies in the definition
      of 'stone-free', which reflect variations in the type of imaging used to assess
      the presence of stones postoperatively and the timing of the assessment. Other
      possible factors such as the importance of residual fragments following stone
      surgery, and the size and position of the stones might also account for
      variations in stone-free rates. In order to obtain an accurate estimate of the
      SFR, especially within subgroups defined by stone characteristics and exact
      technique, we compare reported SFRs from studies that use imaging other than CT
      for follow-up and those that use only CT. We also review the evidence on the
      importance of active retrieval of fragments during flexible URS and whether this
      technique improves the outcomes of patients with kidney stones. 

PMID- 25868565
TI  - Call for early prevention: prevalence rates of overweight among Turkish and
      Moroccan children in The Netherlands.
AB  - BACKGROUND: Monitoring overweight in risk groups is necessary. Our aim is to
      assess the trend in overweight and obesity in Turkish and Moroccan children in
      the Netherlands since 1997 and to monitor the levels of lifestyle-related
      behaviours in 2009. METHODS: We selected cross-sectional data of Turkish and
      Moroccan children aged 2-18 years from two national Growth Studies performed in
      1997 and 2009 in the Netherlands. Lifestyle-related behaviours were obtained in
      the 2009 study by questionnaire. RESULTS: In 2009, 31.9% of Turkish and 26.6% of
      Moroccan children had overweight, whereas this was, respectively, 26.7% and 19.6%
      in 1997. Already at 2 years, 21.1% in Turkish and 22.7% in Moroccan children had
      overweight in 2009. The prevalence of obesity was above 4% from 3 years onwards.
      High (i.e. >= 25%) prevalence rates of unhealthy lifestyle-related behaviours
      were found for not having breakfast (26-49%) among Turkish and Moroccan
      adolescent (i.e. 15-18 years) girls, consuming no fruit (29-45%) and watching
      TV/PC >= 2 h (35-72%) among all Turkish and Moroccan adolescents, no
      walking/cycling to school/day care among preschool children (2-4 years) (28-56%)
      and adolescents (34-94%), drinking >= 2 glasses of sweet beverages (44-74%) and
      being <1 h physically active (29-65%) among all children. CONCLUSION: An upward
      trend of overweight and obesity occurred in Turkish and Moroccan children.
      Already at 2 years of age, one out of five Turkish and Moroccan children had
      overweight, which calls for early prevention with attention to specific lifestyle
      related behaviours.

PMID- 25868564
TI  - Tumour and patient factors in renal cell carcinoma-towards personalized therapy.
AB  - Renal cell carcinoma (RCC) comprises a heterogeneous group of histologically and
      molecularly distinct tumour subtypes. Current targeted therapies have improved
      survival in patients with advanced disease but complete response occurs rarely,
      if at all. The genomic characterization of RCC is central to the development of
      novel targeted therapies. Large-scale studies employing multiple 'omics'
      platforms have led to the identification of key driver genes and commonly altered
      pathways. Specific molecular alterations and signatures that correlate with
      tumour phenotype and clinical outcome have been identified and can be harnessed
      for patient management and counselling. RCC seems to be a remarkably diverse
      malignancy with significant intratumour and intertumour genetic heterogeneity.
      The tumour microenvironment is increasingly recognized as a vital regulator of
      RCC tumour biology. Patient factors, including immune response and drug
      metabolism, vary widely, which can lead to widely divergent responses to drug
      therapy. Intratumour heterogeneity poses a significant challenge to the
      development of personalized therapies in RCC as a single biopsy might not
      accurately represent the clonal population ultimately responsible for aggressive
      biologic behaviour. On the other hand, the diversity of genomic alterations in
      RCC could also afford opportunities for targeting unique pathways based on
      analysis of an individual tumour's molecular composition. 

PMID- 25868566
TI  - Contribution of overweight and obesity to adverse pregnancy outcomes among
      immigrant and non-immigrant women in Berlin, Germany.
AB  - BACKGROUND: Maternal excessive weight and smoking are associated with an
      increased risk of pregnancy complications and adverse pregnancy outcomes. In
      Germany, immigrant women have a higher prevalence of pre-pregnancy
      overweight/obesity compared with autochthonous women. We compared the
      contribution of pre-pregnancy overweight/obesity to adverse pregnancy outcomes
      among immigrant and autochthonous women in Berlin/Germany. METHODS: Data from
      2586 immigrant women (from Turkey, Lebanon, other countries of origin) and 2676
      autochthonous women delivering in three maternity hospitals of Berlin within 12
      months (2011/2012) was used. Cox regression models were applied to estimate the
      association between overweight/obesity and smoking with the outcomes large-for
      gestational-age (LGA), small-for-gestational-age (SGA), preterm birth (PTB) and
      extreme preterm-birth (E-PTB). Population attributive fractions (PAF) were
      calculated to quantify the proportion of the outcomes attributable to
      overweight/obesity and smoking, respectively. RESULTS: Prevalence of overweight
      and obesity was 33.4% among autochthonous and 53.6% among Turkish women.
      Prevalence risk ratios of excessive weight were highest for LGA infants among
      immigrant and autochthonous women. The PAFs were -11.8% (SGA), +16.3% (LGA),
      +3.6% (PTB) and +16.5% (E-PTB) for the total study population. CONCLUSIONS:
      Overweight/obesity is strongly associated with an increased risk of delivering an
      LGA infant among both immigrant and autochthonous women. Compared with
      autochthonous women, the contribution of excessive weight to LGA is even higher
      among immigrant women, in whom PAFs of overweight/obesity even exceed those of
      smoking for some outcomes.

PMID- 25868567
TI  - The frequency of using herbal medicines among patients with hypertension in
      Kerman, Iran, 2012-2013.
AB  - INTRODUCTION: The use of medicinal plants has dramatically increased in recent
      years. Given the increasing rate of hypertension and medical plants usage by
      these patients and considering drug interactions due to concomitant use with
      drugs, the present study aims to evaluate the rate of medicinal plants usage in
      hypertensive patients. METHODS: This is a cross-sectional study (descriptive
      analytical) in which 650 hypertensive patients referring to the subspecialty
      clinic of Kerman were questioned about medicinal plants usage by a medicinal
      plants questionnaire. Among these patients, there were 612 who consented to
      participate. After the variables were described, the data were finally analyzed
      using Stata 12. RESULTS: The average age of those using these drugs in the past
      year was 58.8 +/- 10 years. Of the total number of participants using medicinal
      plants, there were 58 males (23.5%) and 122 females (33.4%). There were 129
      participants (72.5%) using medicinal plants through self-administration, 17
      participants (9.5%) on experienced users' advice, 16 participants (9%) as
      administered by herbalists, and 11 participants (6%) as administered by doctors.
      However, the most important resources for using a drug that prevents hypertension
      were family and friends (74 participants; 41.5%) and doctors (13 participants;
      7.3%). According to the results, there was no significant difference between the
      level of education and medicinal plants usage (P = .95); however, there was a
      significant difference between gender and medicinal plants usage (P = .009).
      DISCUSSION: According to the results indicating the relatively high prevalence of
      medicinal plants usage and their arbitrary use by hypertensive patients without
      consulting a specialist, it seems necessary to plan for more effective and secure
      public education and train people to provide herbal drug services for various
      diseases with hypertension being the most common one.

PMID- 25868568
TI  - Immunomodulatory Properties of Taranjebin (Camel's Thorn) Manna and Its Isolated
      Carbohydrate Macromolecules.
AB  - Taranjebin manna is a substance produced by Poophilus nebulosus Leth.
      (Aphrophoridae) larva that feed from host plant Alhagi maurorum (Leguminosae). In
      Persian ethnomedicine, it is used as an antipyretic, antiviral, antimicrobial,
      demulcent, and adaptogen. But it is contraindicated in acute fever and some
      infections. This controversy might be due to its immunomodulatory properties.
      This study evaluated immunomodulatory properties of Taranjebin and its
      macromolecules. Taranjebin solution was prepared as described in traditional
      literature. After dialysis and precipitation, the macromolecules were isolated on
      DEAE Sephadex A-25. The cytotoxic/proliferative properties of Taranjebin and its
      isolated macromolecules on human Jurkat E6.1 cells were investigated (15.62-1000
      MUg/mL) using WST-1 reagent. Three of 4 isolated acidic polysaccharides inhibited
      the proliferation of Jurkat cells in a dose-dependent manner at concentrations
      higher than 31.25 MUg/mL (IC50 range of 44.81-147.97 MUg/mL). The crude aqueous
      Taranjebin solution had proliferative effects. These results indicate the
      immunomodulatory properties of Taranjebin.

PMID- 25868569
TI  - [Dermatology in Cambodia: Sustainable establishment of a medical discipline].
AB  - After almost 25 years of dictatorship and civil war, in the mid 1990s, Cambodia
      was in dire need of improvement of its medical infrastructure on all levels.
      Attention had already been focused on establishing primary care services such as
      emergency surgery, paediatrics and gynaecology/obstetrics; however
      dermatovenereology services had so far not been addressed. Using a comprehensive
      approach aiming at sustainable development, German, French and Cambodian
      institutions worked together to identify four core areas in need of improvement:
      postgraduate training, development of skin clinics, quality management, and
      integration of dermatology services into the health insurance scheme. Since 2005,
      this "Masterplan Dermatology" was financially supported by the Centre for
      International Migration and Development (CIM) based in Frankfurt am Main and Else
      Kroner Fresenius-Stiftung (EKFS) based in Bad Homburg auf der Hohe. Significant
      improvements have been made due to the efforts of the above institutions with the
      support of the donors; however challenges of this complex endeavor still remain.

PMID- 25868570
TI  - [Chronic venous insufficiency: Update on pathophysiology, diagnosis and
      treatment].
AB  - Chronic venous insufficiency is very common and has an important socioeconomic
      impact. It is associated with a high morbidity for the patients and causes high
      costs for the healthcare systems. In recent years novel treatment modalities have
      evolved and their efficacy has been evaluated in many studies. Knowledge of
      pathophysiology, the diagnostic procedures and therapeutic options for chronic
      venous insufficiency is important for effective treatment of affected patients. 

PMID- 25868571
TI  - [Tropical and travel-related dermatomycoses: Part 1: Dermatophytoses].
AB  - Today, tropical and travel-related dermatomycoses must be increasingly
      anticipated to present in dermatological offices and clinics. Skin infections due
      to dermatophytes or other fungi may occur after a journey in countries with a
      high prevalence for the respective causative fungal pathogen, e.g., tinea
      corporis due to Trichophyton soudanense. Otherwise, more frequently, single
      infections and even localized outbreaks due to "exotic" or "imported" pathogens
      of dermatophytoses occur. These epidemics are observed in childcare facilities in
      Germany and in other European countries. Source of infection are immigrants from
      Africa and sometimes from Asian countries. Furthermore, African children, and
      sometimes also adults, are often only asymptomatic carriers of such
      anthropophilic dermatophytes. Outbreaks of dermatophyte infections with one and
      more affected children and also adult staff and teachers due to Trichophyton
      violaceum or Microsporum audouinii in kindergartens and schools are not a rarity
      these days. Further tropical and travel-associated dermatophytes are Trichophyton
      tonsurans, Trichophyton schoenleinii, and Trichophyton concentricum. Tinea
      capitis should be treated in a species-specific manner. Griseofulvin is the
      treatment of choice for infections due to Microsporum species. In contrast, tinea
      capitis due to Trichophyton species has to be treated by terbinafine, however,
      because the agent is not approved for children in Germany, only after receiving
      written consent of parents. Alternatives are fluconazole and itraconazole. Onset
      and aggravation of tinea pedis during travel has its origin in a preexisting
      neglected fungal infection of the feet. In the tropics, exacerbations and
      secondary bacterial complications of tinea pedis develop under distinctly
      promoting conditions.

PMID- 25868572
TI  - Protected area certificates: gaining ground for better ecosystem protection?
AB  - Protected areas are vital to sustain a number of ecosystem services. Yet, many
      protected areas are underfinanced and lack management effectiveness. Protected
      area certificates have been suggested as a way to resolve these problems. This
      instrument would allow land managers to certify an area if it meets certain
      conservation criteria. The certificates could then be sold on an international
      market, for example to companies and any consumers that are interested in
      environmental protection. Some pilot initiatives have been launched, yet little
      is known about future demand and features of protected area certificates. To fill
      this knowledge gap, we conduct a choice experiment with close to 400 long
      distance tourists from Germany as a potential group of buyers. Our results
      indicate that the respondents have the highest willingness to pay for
      certificates that conserve sensitive ecosystems and in addition to this lead to
      poverty reduction and safeguard water resources. For other attributes such as a
      greenhouse gas reduction, the preferences are less significant. Overall, the
      results are rather homogenous irrespective of where the protected areas are
      located. These insights are important for the future design and marketing of
      protected area certificates. 

PMID- 25868573
TI  - The Influence of the Disturbed Continuity of the River and the Invasive Species-
      Potamopyrgus antipodarum (Gray, 1843), Gammarus tigrinus (Sexton, 1939) on
      Benthos Fauna: A Case Study on Urban Area in the River Ruda (Poland).
AB  - The progressive degradation of aquatic ecosystems and ecohydrological role of
      rivers is one of the most important global environmental issues. The loss of the
      ability of rivers to self-purify waters due to the disturbances of river
      continuity cause a lack of biological life in parts of rivers or even in an
      entire river. The appearance of alien species in degraded aquatic environments is
      an increasingly common phenomenon and constitutes one of the threats to
      biodiversity. The aim of the study was to evaluate the possible impact of alien
      species Potamopyrgus antipodarum (Gray, 1843) and Gammarus tigrinus (Sexton,
      1939) on native invertebrates as well as the influence of environmental factors
      on the occurrence benthos fauna including also alien species. The study conducted
      in industrial area, in the River Ruda (Poland), showed that at the sites at which
      the occurrence of the two alien species was observed, the density of native
      benthos and diversity decreased significantly. CCA analysis showed that non
      native species occurred in fast water velocity and that their presence was
      associated with high values of conductivity, hardness, and a high chloride
      content. The arrival of new species from other geographical areas is one of the
      factors that influences the species balance in native aquatic fauna. The number
      of alien species in freshwater ecosystems probably will increase in the future as
      new aliens are moved outside of their native ranges. 

PMID- 25868574
TI  - Fabrication and optical probing of highly extended, ultrathin graphene
      nanoribbons in carbon nanotubes.
AB  - Nanotemplated growth of graphene nanoribbons (GNRs) inside carbon nanotubes is a
      promising mean to fabricate ultrathin ribbons with desired side edge
      configuration. We report the optical properties of the GNRs formed in single-wall
      carbon nanotubes. When coronene is used as the precursor, extended GNRs are grown
      via a high-temperature annealing at 700  degrees C. Their optical responses are
      probed through the diazonium-based side-wall functionalization, which effectively
      suppresses the excitonic absorption peaks of the nanotubes without damaging the
      inner GNRs. Differential absorption spectra clearly show two distinct peaks
      around 1.5 and 3.4 eV. These peaks are assigned to the optical transitions
      between the van Hove singularities in the density of state of the GNRs in
      qualitative agreement with the first-principles calculations. Resonance Raman
      spectra and transmission electron microscope observations also support the
      formation of long GNRs. 

PMID- 25868575
TI  - Testicular Adnexal Smooth Muscle Hyperplasia: A Mimic of Malignancy.

PMID- 25868576
TI  - National Trends in Followup Imaging after Pyeloplasty in Children in the United
      States.
AB  - PURPOSE: Radiographic followup after pyeloplasty for the correction of
      ureteropelvic junction obstruction is not well defined in children. We
      characterize trends in frequency and modality of postoperative imaging after open
      and minimally invasive pediatric pyeloplasty. MATERIALS AND METHODS: Using the
      MarketScan(r) database, we identified patients 0 to 18 years old undergoing
      pyeloplasty between 2007 and 2013. Followup imaging was classified as functional
      (diuretic renography, excretory urography) or nonfunctional (ultrasound,
      computerized tomography, magnetic resonance imaging). We excluded patients with
      less than 24 months of postoperative enrollment in MarketScan. Multivariate
      logistic regression was performed to determine associations between demographic
      variables and imaging use patterns. RESULTS: We identified 926 patients with a
      mean +/- SD followup of 3.6 +/- 1.3 years, of whom 30% underwent minimally
      invasive pyeloplasty. Overall 5.9% of patients had no postoperative imaging
      available. Within the first 6 months postoperatively 853 patients (91%) underwent
      at least 1 imaging study and 192 (24%) underwent renography. Within the first 12
      months postoperatively 91% of patients underwent at least 1 imaging study, most
      commonly ultrasound. After 12 months almost a third of the patients were not
      followed with imaging. Of the 71% undergoing imaging most underwent ultrasound.
      Younger age and female gender were independently associated with frequent imaging
      (at least yearly) on multivariate logistic regression. CONCLUSIONS: Following
      pediatric pyeloplasty there is variation in modality and frequency of imaging
      followup. The majority of patients are followed with renal ultrasound, with less
      frequent use of functional imaging. Almost a third of patients do not undergo
      followup imaging after 1 year.

PMID- 25868577
TI  - Dietary supplement 4-methylumbelliferone: an effective chemopreventive and
      therapeutic agent for prostate cancer.
AB  - BACKGROUND: Prevention and treatment of advanced prostate cancer (PCa) by a
      nontoxic agent can improve outcome, while maintaining quality of life. 4
      methylumbelliferone (4-MU) is a dietary supplement that inhibits hyaluronic acid
      (HA) synthesis. We evaluated the chemopreventive and therapeutic efficacy and
      mechanism of action of 4-MU. METHODS: TRAMP mice (7-28 per group) were gavaged
      with 4-MU (450mg/kg/day) in a stage-specific treatment design (8-28, 12-28, 22-28
      weeks). Efficacy of 4-MU (200-450mg/kg/day) was also evaluated in the PC3
      ML/Luc(+) intracardiac injection and DU145 subcutaneous models. PCa cells and
      tissues were analyzed for HA and Phosphoinositide 3-kinase (PI-3K)/Akt signaling
      and apoptosis effectors. HA add-back and myristoylated Akt (mAkt) overexpression
      studies evaluated the mechanism of action of 4-MU. Data were analyzed with one
      way analysis of variance and unpaired t test or Tukey's multiple comparison test.
      All statistical tests were two-sided. RESULTS: While vehicle-treated transgenic
      adenocarcinoma of the prostate (TRAMP) mice developed prostate tumors and
      metastases at 28 weeks, both were abrogated in treatment groups, without
      serum/organ toxicity or weight loss; no tumors developed at one year, even after
      stopping the treatment at 28 weeks. 4-MU did not alter the transgene or
      neuroendocrine marker expression but downregulated HA levels. However, 4-MU
      decreased microvessel density and proliferative index (P < .0001,). 4-MU
      completely prevented/inhibited skeletal metastasis in the PC3-ML/Luc(+) model and
      DU145-tumor growth (85-90% inhibition, P = .002). 4-MU also statistically
      significantly downregulated HA receptors, PI-3K/CD44 complex and activity, Akt
      signaling, and beta-catenin levels/activation, but upregulated GSK-3 function, E
      cadherin, and apoptosis effectors (P < .001); HA addition or mAkt overexpression
      rescued these effects. CONCLUSION: 4-MU is an effective nontoxic, oral
      chemopreventive, and therapeutic agent that targets PCa development, growth, and
      metastasis by abrogating HA signaling.

PMID- 25868579
TI  - Gemcitabine/dexamethasone/cisplatin vs cytarabine/dexamethasone/cisplatin for
      relapsed or refractory aggressive-histology lymphoma: cost-utility analysis of
      NCIC CTG LY.12.
AB  - BACKGROUND: The NCIC CTG LY.12 study showed that gemcitabine, dexamethasone, and
      cisplatin (GDP) were noninferior to dexamethasone, cytarabine, and cisplatin
      (DHAP) in patients with relapsed or refractory aggressive histology lymphoma
      prior to autologous stem cell transplantation. We conducted an economic
      evaluation from the perspective of the Canadian public healthcare system based on
      trial data. METHODS: The primary outcome was an incremental cost utility analysis
      comparing costs and benefits associated with GDP vs DHAP. Resource utilization
      data were collected from 519 Canadian patients in the trial. Costs were presented
      in 2012 Canadian dollars and disaggregated to highlight the major cost drivers of
      care. Benefit was measured as quality-adjusted life-years (QALYs) based on
      utilities translated from prospectively collected quality-of-life data. All
      statistical tests were two-sided. RESULTS: The mean overall costs of treatment
      per patient in the GDP and DHAP arms were $19 961 (95% confidence interval (CI) =
      $17 286 to $24 565) and $34 425 (95% CI = $31 901 to $39 520), respectively, with
      an incremental difference in direct medical costs of $14 464 per patient in favor
      of GDP (P < .001). The predominant cost driver for both treatment arms was
      related to hospitalizations. The mean discounted quality-adjusted overall
      survival with GDP was 0.161 QALYs and 0.152 QALYs for DHAP (difference = 0.01
      QALYs, P = .146). In probabilistic sensitivity analysis, GDP was associated with
      both cost savings and improved quality-adjusted outcomes compared with DHAP in
      92.6% of cost-pair simulations. CONCLUSIONS: GDP was associated with both lower
      costs and similar quality-adjusted outcomes compared with DHAP in patients with
      relapsed or refractory lymphoma. Considering both costs and outcomes, GDP was the
      dominant therapy.

PMID- 25868578
TI  - Female breast cancer incidence among Asian and Western populations: more similar
      than expected.
AB  - BACKGROUND: Previous reports suggested that female breast cancer is associated
      with earlier ages at onset among Asian than Western populations. However, most
      studies utilized cross-sectional analyses that may be confounded by calendar
      period and/or birth cohort effects. We, therefore, considered a longitudinal
      (forward-looking) approach adjusted for calendar-period changes and conditioned
      upon birth cohort. METHODS: Invasive female breast cancer data (1988-2009) were
      obtained from cancer registries in China, Hong Kong, South Korea, Taiwan,
      Singapore, and the United States. Age-period-cohort models were used to
      extrapolate longitudinal age-specific incidence rates for the 1920, 1944, and
      1970 birth cohorts. RESULTS: Cross-sectional age-specific incidence rates rose
      continuously until age 80 years among US white women, but plateaued or decreased
      after age 50 years among Asian women. In contrast, longitudinal age-specific
      rates were proportional (similar) among all Asian countries and the United States
      with incidence rates rising continuously until age 80 years. The extrapolated
      estimates for the most recent cohorts in some Asian countries actually showed
      later ages at onset than in the United States. Additionally, over successive
      birth cohorts, the incidence rate ratios (IRRs) for the longitudinal curves
      converged (narrowed) between Asian and US white women. CONCLUSIONS: Similar
      longitudinal age-specific incidence rates along with converging IRRs indicate
      that the age effects for invasive breast cancer are more similar among Asian and
      Western populations than might be expected from a solely cross-sectional
      analysis. Indeed, the Asian breast cancer rates in recent generations are even
      surpassing the historically high rates in the United States, highlighting an
      urgent need for efficient prevention and treatment strategies among Asian
      populations.

PMID- 25868580
TI  - Is There a Link Between Expression Levels of Histone
      Deacetylase/Acetyltransferase in Mouse Sperm and Subsequent Blastocyst
      Development?
AB  - Histone acetylation has been known to be significant in spermatogenesis. Histone
      acetylation is regulated by the act of histone deacetylases (HDACs) and histone
      acetyltransferases (HATs). We investigated the link between expression levels of
      HDACs and HATs in mouse sperm and subsequent blastocyst formation rate. In the
      univariate analysis, expression levels of HDAC1 and HAT were generally not
      associated with the blastocyst formation rate. When divided by the mature oocyte
      number category, a significant positive association was observed between the
      expression levels of HDAC1 and the blastocyst-forming rate in the highest (>
      75th) percentile group (a group with >=34 mature oocytes). In conclusion,
      expression of sperm HDAC1 could be considered as a possible predictor of embryo
      development in mice with high ovarian response. 

PMID- 25868581
TI  - Morphological Changes and Expression of Cytokine After Local Endometrial Injury
      in a Mouse Model.
AB  - OBJECTIVE: To establish a mouse model for endometrial injury and determine the
      underlying mechanism regarding its favorable effect on embryo implantation. STUDY
      DESIGN: Female Kunming mice were randomly allocated into 4 groups: group I,
      normal control; group II, injury procedure control; and group III and group IV,
      the mice being scratched with a blunt syringe on the right uterine horn or both,
      respectively. All the mice were mated with the males during the next estrus
      phase. The number of implanted embryos on each side of uterus was calculated on
      day 8 of pregnancy. The endometrial samples were taken on day 4 of pregnancy, and
      the local morphological changes and cytokine expressions were examined. RESULTS:
      Compared to group II, our results showed that in group IV (1) there were
      significantly higher numbers of implanted embryos, (2) the endometrial glands and
      vasculatures in stroma were obviously increased and the pinopodes were abundant
      and well developed, and (3) the local levels of cytokines leukemia inhibitory
      factor (LIF) and oncostatin M (OSM) messenger RNA and protein expression were
      significantly increased. CONCLUSIONS: Local mechanical injury on mouse uteri
      enhanced endometrial receptivity and improved embryo implantation, which were
      correlated with the characteristic changes in endometrial morphology and the
      upregulation of LIF and OSM gene and protein expression.

PMID- 25868583
TI  - Who audits the autopsy?

PMID- 25868582
TI  - Potential Therapy for Neisseria Gonorrhoeae Infections With Human Chorionic
      Gonadotropin.
AB  - The scientific evidence suggests that Neisseria gonorrhoeae (NG) infects human
      fallopian tubes by molecular mimicry in which pathogens act like a ligand to bind
      to epithelial cell surface human chorionic gonadotrophin (hCG)/luteinizing
      hormone (LH) receptors. The hCG-like molecule has been identified as ribosomal
      protein L12 in NG coat surface. Human fallopian tube epithelial cells have been
      shown to contain functional hCG/LH receptors. As previously shown in human
      fallopian tube organ and cell culture studies, cellular invasion and infection
      can be prevented by exposing the cells to excess hCG, which would outnumber and
      outcompete NG for receptor binding. Based on these data, we suggest testing hCG
      in clinical trials on infected women. 

PMID- 25868584
TI  - Sixth ISALM Hamburg, Germany September 2005 : Organized by the German Society of
      legal medicine-Japanese Society of legal medicine in cooperation with the German
      Japanese Association of Jurists.

PMID- 25868585
TI  - Immunoassays for drug screening in urine : Chances, challenges, and pitfalls.
AB  - Immunoassays are presently used worldwide for the rapid screening of drugs.
      Despite the fact that they are a highly valuable tool for the testing of legal
      and illicit drugs, there is a real risk of false-positive and false-negative
      findings and many pitfalls must be taken into account when these tests are used
      in an uncritical manner and without valid confirmation procedures. In a long
      standing successful cooperation with a large psychiatric hospital, we checked
      doubtful and nonplausible immunochemical findings in urine with gas
      chromatography-mass spectrometry (GC-MS) confirmation methods. The reported case
      histories demonstrate typical pitfalls, for example, influence of changing
      nutritional habits, use of sweeteners (cyclamate), uncritical creatinine
      correction, impaired elimination, or cross-reactivities of simultaneous
      therapeutic medication. In accordance with national and international
      associations, immunoassays are recommended as a useful tool for screening.
      However, confirmation analysis with conclusive methods (GC-MS or liquid
      chromatography-MS) is unavoidable for valid substance identification,
      discrimination between active and inactive metabolites, detection of congeners,
      and accurate determination of concentrations in body fluids. 

PMID- 25868586
TI  - Age determination of brain contusions.
AB  - In 104 individuals who had sustained traumatic brain injury, the course of
      traumatically induced morphological changes was investigated
      immunohistochemically during the first 30 weeks after the trauma. Regarding the
      inflammatory cell reaction in human cortical contusions, CD15-labeled
      granulocytes were detectable within 10 minutes following brain injury, whereas
      significantly increased numbers of nuclear leukocytes occurred after a
      postinfliction interval of at least 1.1 days (leukocyte common antigen), 2 days
      (CD3), or 3.7 days (UCHL-1), respectively. A positive nuclear staining for the
      proliferation marker MIB-1 by cerebral macrophages could be observed as early as
      3 days after the injury and regularly in cases with a survival between 7 and 11
      days. Injury-induced glial staining reactions could be demonstrated, at the
      earliest, after a postinfliction interval of 3 hours for alpha1-antichymotrypsin,
      22 hours for vimentin, 1 day for glial fibrillary acidic protein, and 7 days for
      tenascin. Regarding the vascular response to brain injury, a significantly
      increased immunoreactivity could be detected in cortical contusions with a wound
      age of at least 3 hours for factor VIII, 1.6 days for tenascin, and 6.8 days for
      thrombomodulin, whereas the immunostaining for laminin and type IV collagen was
      regularly whereas the immunostaining for laminin and type IV collagen was
      regularly positive even in the vascular endothelium of ininjured brain tissue. 

PMID- 25868587
TI  - Examination of postmortem animal interference to human remains using cross
      species multiplex PCR.
AB  - Postmortem animal interference may be confused at first sight with injuries of
      vital origin, thus arousing suspicion of external violence preceding death. A
      reliable classification of the origin of such doubtful injuries is of crucial
      importance, a fact that is especially true for the investigation of suspected
      homicide and/or mammade body mutilation after death. In forensic pathology, the
      identification of injuries as caused by animals postmortem and the classification
      of a particular species as responsible for a specific injury pattern under
      question is usually done by forensic pathologists with vast practical experience
      and special knowledge of the appearance and morphology of tooth marks of
      carnivores and rodents, respectively. However, a molecular biological
      investigation of such wounds could provide genetic evidence that an injury
      pattern present on a corpse was truly caused postmortem by animal interference
      and thus support the pathologist's expertise. For this purpose, we developed a
      panel of small species-specific short-tandem repeat systems (<150 bp) for animals
      typically involved in postmortem scavenging of human remains, such as dogs and
      cats as well as wild-living rodents (mice and rats) having possible access to
      death scenes inside apartments or buildings. A specific and sensitive cross
      species multiplex polymerase chain reaction was then established including the
      species-specific animal markers, thus enabling the genetic identification of
      wounds caused postmortem by different animals on human remains. 

PMID- 25868588
TI  - Immunohistochemical expression of tumor necrosis factor-alpha in sepsis-induced
      lung injury.
AB  - Sepsis is asevere, systemic inflammatory disease caused by various kinds of
      microbes. In the present study, we immunohistochemically examined tumor necrosis
      factor (TNF)-alpha expression in sepsis-induced lung injury, and discuss its
      availability for the postmortem diagnosis of sepsis. Lung samples were obtained
      from different lung lobes of nine sepsis and eight control cases with postmortem
      intervals between 12 and 48 hours. Immunohistochemical analysis using anti-human
      TNF-alpha rabbit polyclonal antibodies was carried out. In sepsis and control
      groups, immunoreactivity for TNF-alpha was strongly detected in round-shaped
      mononuclear cells. The intensity of the immunohistochemical staining reaction was
      homogeneous in all lobes of the lungs examined. Furthermore, a double-color
      immunofluorescence analysis revealed that macrophages were a main cellular source
      of TNF-alpha in the lungs. To semiquantitatively evaluate the expression of TNF
      alpha in the lungs, the ratios of the number of TNF-alpha-positive macrophages to
      total number of macrophages were calculated. Morphometrically, in lungs of the
      sepsis group, the ratio of TNF-alpha-positive macrophages was significantly
      higher, compared with the control group. TNF-alpha expression in the lungs can
      become a clue for the postmortem diagnosis of pulmonary inflammation, especially,
      TNF-alpha-positive ratios of 20% of more might suggest sepsis as the cause of
      death. 

PMID- 25868589
TI  - Sudden cardiovascular death associated with sexual activity : A forensic autopsy
      study (1972-2004).
AB  - In recent discussions about potency-enhancing drugs such as sildenafil, health
      hazards associated with sexual activity have attracted increasing attention (1).
      In a medicolegal postmortem study performed in the Center of Legal Medicine at
      the University Hospital in Frank furt/Main over a 33-year period (1972-2004),
      about 32,000 forensic autopsies revealed 68 (0.22%) natural deaths occurring
      during sexual activity. Except for 5 women (7.4%; average age 39.8 years), in
      most cases, men were involved (92.6%; average age 59.1 years). The most frequent
      cause of death was myocardial infarction (n=28; 41.2%). In three cases,
      pericardial tamponade accompanied by myomalacia were observed. In 20 patients
      (29.4%), coronary artery disease (CAD) without signs of acute myocardial
      infarction (MI) was diagnosed. The medical history of 19 of the deceased
      indicated previous MI. There were seven cerebral hemorrhages (10.3%). The annual
      incidence of sudden cardiovascular death during sexual activity is estimated to
      be 1.9 per 1000 autopsies for men and 0.16 per 1000 autopsies for women (1). It
      is necessary to inform patients with CAD about prodromes and risk in relation to
      any form of physical and/or emotional stress. 

PMID- 25868590
TI  - Neuropathological alterations in drug abusers : The involvement of neurons,
      glial, and vascular systems.
AB  - Because the effects of drug abuse on the cellular elements of the human brain
      have not been studied systematically, an investigation was performed using
      histology, immunohistochemistry, and morphometry. The main cortical and
      subcortical brain areas of 50 polydrug deaths were analyzed as compared with
      controls.In the brains of drug abusers, a significant neuronal loss was present.
      Interestingly, the number of glial fibrillary acidic protein (GFAP)-positive
      astrocytes was reduced. the numerical density of perivascular and parenchymal
      microglia was increased in the white matter and in most subcortical regions. In
      the white matter there were widespread beta-amyloid precursor protein deposits.
      Furthermore, there was a prominent vascular hyalinosis, endothelial cell
      proliferation, and a loss of immunoreactivity for collagen type IV within the
      vascular basal lamina.The neuronal loss seems to be the result of a direct
      impairment of nerve cells and, indirectly, to a damage of astrocytes, axons, and
      the microvasculature. The reduction of GFAP-positive astrocytes is also
      indicative of a drug-induced damage. The axonal injury suggests a toxic-metabolic
      drug effect, whereas the concomitant activation of microglia is indicative of a
      long-standing progressive process. The noninflammatory vasculopathy can be
      considered as the morphological substrate of a disturbed blood-brain barrier. Our
      findings demonstrate that drugs of abuse initiate a cascade of interacting toxic,
      vascular, and hypoxic factors that finally result in widespread disturbances
      within the complex network of central nervous system cell-cell interactions. 

PMID- 25868591
TI  - Precision of estimating the time since death using different criteria of
      supravital muscular excitability.
AB  - Supravital electrical excitability of skeletal muscle is an important method of
      estimating the time since death in the early postmortem period, which further
      narrows down the limits of death-time estimation resulting from body cooling.
      Compared with the subjective grading of muscular excitability, the precision of
      death-time estimation could already be raised by objectifying the muscular
      contraction. Criteria for extrapolation of the time since death by objectified
      muscular contraction are decrease of the maximum force using definite stimuli,
      increase of the relaxation time, and increase of the galvanic threshold.In an
      original investigation comprising 71 cases, the first 50 served as reference,
      whereas the remainder served as the control sample.To re-evaluate the data on the
      precision of death-time estimation the data was remodeled and matched reference
      and control samples regarding beginning of the investigation and duration of
      electrical excitability, age, and so on, were formed. Twenty-eight cases were
      available for matched reference and control samples. For the reference group,
      calculations on the accuracy of death-time estimation were carried out and were
      checked with the independent control group. The following questions were examined
      on these remodeled reference and control samples: 1. Would death-time estimation
      be more precise when using the postmortem interval as a dependent or independent
      variable? 2. Are there any differences between contralateral muscle groups? 3.
      Are there differences between muscles in the duration of electrical excitability?
      4. Can the original data on the precision of death-time estimation be confirmed
      on the remodeled reference and control sample? The most relevant new result is
      that when using the postmortem interval as a dependent variable, a much higher
      precision of death-time estimation can be achieved. There are no differences
      between contralateral muscles as far as the criteria for extrapolation of the
      time since death are concerned and the thenar and hypothenar muscles are
      excitable over a much longer period of time than the biceps bracchii muscle. 

PMID- 25868592
TI  - Pediatric forensic pathology : The practice, the prose, and the problems.

PMID- 25868593
TI  - Cane Corso attack : Two fatal cases.
AB  - It is estimated that annually between 1 and 4 million people are bitten by dogs
      in the United States. The vast majority of dog bites produce minor injuries, but
      serious sequelae, and even death, may occur. Annual mortality rates from dog
      attacks are reported at 7.2 cases per 100 million inhabitants each year. Of these
      fatalities, 69,8% involved a pet. Although dog bite-related injuries to humans
      appear to be a breed-specific problem (Pit Bulls and Rottweilers), other breeds
      also may bite and cause fatalities at high rates. Here we present the case of a
      couple slaughtered by their own three Cane Corso, an Italian breed of Molossoid
      dog. Dog bite-related injuries represent a public health problem. Some
      jurisdictions have adopted breed-specific restrictions in order to prevent such
      dog attacks, focusing the attention only on these certain breeds. 

PMID- 25868594
TI  - Ba'alat.

PMID- 25868595
TI  - Late onset thrombosis in two Japanese patients with compound heterozygote protein
      S deficiency.

PMID- 25868596
TI  - Open questions in conducting confirmatory replication studies: Commentary on
      Boekel et al., 2015.

PMID- 25868597
TI  - Glutathione S-transferase T1 and M1 null genotypes and Parkinson's disease risk:
      evidence from an updated meta-analysis.
AB  - Glutathione S-transferase T1 and M1 (GSTT1 and GSTM1) have been reported to be
      associated with Parkinson's disease (PD). However, the results of these previous
      studies were inconsistent. The reported studies were conducted from 1990 to 2014
      by searching PubMed. The total Odds Ratio and 95 % Confidence Interval were
      calculated and analyzed by Review Manager 5.1 and STATA 12. We also did subgroup
      analysis of ethnicity, publication year and sample size of total cases.
      Sensitivity analysis and publication bias were also done to evaluate the
      credibility of the results. A total of 3753 PD patients and 5636 controls from 19
      case-control studies were identified. Overall, no association was observed (OR
      1.01, 95 % CI 0.99-1.21, P = 0.07) between GSTM1 null genotype and PD. There was
      significant association in Caucasians when subgroup analysis of ethnicity was
      performed, and the same conclusion was observed in European and UK. And it was
      also in publication year of 1995-1999 and in sample size of total cases of <90
      and 91-181. However, there was no significant association between GSTT1 null
      genotype and PD risk in this meta-analysis. Publication bias was negligible and
      the overall results were stable by sensitivity analysis. A slight increase of PD
      risk was detected in the meta-analysis of GSTM1 null genotype in subgroup
      analysis of ethnicity, publication year and sample size of total cases. However,
      short of statistical significance was detected for GSTT1 null genotype.

PMID- 25868599
TI  - Management of intracranial atherosclerotic disease: current roles of medical
      therapy versus stent-assisted revascularization.

PMID- 25868598
TI  - Intracranial hemodynamic changes in primary Sjogren syndrome: a transcranial
      Doppler case-control study.
AB  - The aim of this case-control study is to evaluate the cerebral hemodynamic
      parameters in primary Sjogren syndrome patients by means of transcranial Doppler
      and the possible relationship with neuroimaging structural alteration,
      immunological markers and subclinical neurological involvement. 87 consecutive
      treatment-naive outpatients with primary Sjogren syndrome and 86 age- and sex
      matched healthy controls underwent transcranial Doppler for bilateral measurement
      of mean flow velocities, pulsatility index and systolic-diastolic ratio, brain
      magnetic resonance imaging, clinical evaluation with neuropsychological test and
      serological assessment. 28 patients and 4 controls (32 vs. 4 %, p .001) had
      executive function disorders at neuropsychological tests. Mean pulsatility index
      and systolic-diastolic ratio were significantly higher in both mean cerebral
      arteries of the patients than in controls (1.3 +/- 0.6 vs. 0.9 +/- 0.6, p .01 and
      3.4 +/- 1.7 vs. 1.6 +/- 0.7, p .001, respectively). White matter hyperintensities
      were present in 21 patients and 18 controls. Only age was significantly
      associated with WMHs in both groups (p < .0001). The increase in systolic
      diastolic ratio significantly correlates with neuropsychological impairment. Anti
      SSA autoantibodies positively correlate with impaired systolic-diastolic ratio
      and with neuropsychiatric symptoms. The correlation between haemodynamic changes
      and anti-SSA autoantibodies suggests a role for the autoimmune response in
      determining early cerebral hemodynamic dysfunctions. The functional impairment of
      the endothelium may play a pivotal role in vasomotor dysfunction before any
      organic damage. The subsequent structural damage of the arterial wall may be
      responsible for the increase in resistances in small cerebral arteries and
      sustained hypoperfusion.

PMID- 25868600
TI  - Quality Improvement Implementation: Improving Reproducibility in the
      Echocardiography Laboratory.
AB  - BACKGROUND: Interpretative variability can adversely affect echocardiographic
      reliability, but there is no widely accepted method to minimize variability and
      improve reproducibility. METHODS: A continuous quality improvement process was
      devised that involves testing reproducibility by assessment of measurement
      differences followed by robust review, retraining, and retesting. Reproducibility
      was deemed acceptable if >=80% of all interreader comparisons were within a
      prespecified acceptable difference. Readers not meeting this standard underwent
      retraining and retesting until acceptable reproducibility was achieved for the
      following parameters: left ventricular end-diastolic volume, biplane ejection
      fraction, mitral and aortic regurgitation, left ventricular outflow tract
      diameter, peak and mean aortic valve gradients, and aortic valve area. Eight
      hundred interreader comparisons for evaluation of reproducibility were generated
      from five readers interpreting 10 echocardiograms per testing cycle. The
      applicability and efficacy of this method were then evaluated by testing a second
      larger group of 10 readers and reevaluating reproducibility 1 year later.
      RESULTS: All readers demonstrated acceptable reproducibility for biplane ejection
      fraction, mitral regurgitation, and peak and mean aortic valve gradients.
      Acceptable reproducibility for left ventricular end-diastolic volume, aortic
      regurgitation, and aortic valve area was achieved by four of five readers. No
      readers attained acceptable reproducibility on initial evaluation of left
      ventricular outflow tract diameter. After review and retraining, all readers
      demonstrated acceptable reproducibility, which was maintained on subsequent
      testing 1 year later. A second larger group of 10 readers was also evaluated and
      yielded similar results. CONCLUSIONS: A continuous quality improvement process
      was devised that successfully reduced interpretative variability in
      echocardiography and improved reproducibility that was sustained over time.

PMID- 25868601
TI  - Relative resistance of Menz and Washera sheep breeds to artificial infection with
      Haemonchus contortus in the highlands of Ethiopia.
AB  - The aim of this study was to evaluate the relative resistance of Menz and Washera
      sheep breeds to artificial infection with Haemonchus contortus. The challenge
      trial was conducted at the Debre Berhan Agricultural Research Center in Ethiopia.
      A total of 39 (Menz = 21, Washera = 18) lambs of about 6 months old were used for
      the trial. All lambs were initially treated against internal parasite using
      albendazole and Fasinex to free them from internal parasites and kept indoors. H.
      contortus third-stage larvae (L3) were prepared according to standard procedure
      from adult female parasite collected from abattoirs and recovered using the
      Baerman technique. Approximately 5000 infective larvae were inoculated to the
      experimental lambs at about 5 weeks after deworming. Fecal egg count (FEC),
      packed cell volume (PCV), FAffa MAlan CHArt (FAMACHA) score, lamb body weight,
      and survival of lambs were recorded at 28, 35, and 42 days after challenge. Breed
      effect was not significant (P > 0.05), whereas time of measurement and the
      interaction of breed and time had significant (P < 0.05) effects on FEC and PCV.
      At 28 days after challenge, Menz sheep had lower FEC than Washera sheep, whereas
      at days 35 and 42, the Washera sheep had lower FEC than Menz lambs. The PCV
      decreased significantly throughout the post-challenge period. Despite their
      parasite burden, Menz sheep were able to maintain live weight during the 42 days
      of challenge. Chi-square tests for breed differences in lamb survival were not
      significant at any time (28, 35, and 42 days after challenge). Lower FEC at 28
      days and delayed rise in FEC after infection in Menz lamb would allow in delaying
      anthelmintic treatment. In addition to maintain body weights during the infection
      period, sheep of both breeds exhibited substantial variability in PCV and FEC,
      suggesting opportunity to consider parasite resistance in selection program. 

PMID- 25868602
TI  - Unique microenvironmental responses to PDGF stimulation in brain and spinal cord
      gliomas determine tumor phenotype.
AB  - Injection of a PDGF-B expressing retrovirus into the subcortical white matter of
      adult rats induces the rapid formation of brain tumors that have the histological
      features of glioblastoma. In contrast, when the same retrovirus is injected into
      the spinal cord of adult rats the resulting tumors are more indolent and display
      a unique histology characterized by nests of tumor cells separated by a dense
      vascular network without areas of necrosis. To study whether these differences
      are determined by the tumor cell of origin or due to microenvironmental
      influences, we conducted a series of transplantation experiments. Cells were
      independently isolated from PDGF-induced brain and cord tumors then subsequently
      transplanted into naive rat forebrains and spinal cords. The resulting tumors
      were characterized by histological analysis, marker expression profiling, PDGFR
      subtyping, and latency to tumor-induced morbidity. Tumor phenotypes were found to
      be consistently predicted by the tissue into which they were transplanted rather
      than by the tissue of origin. These results suggest that tumor microenvironment
      rather than the tumor cell of origin may be the primary determinant of glioma
      phenotype in the model presented. 

PMID- 25868603
TI  - Prevalence and characterization of exercise oscillatory ventilation in apparently
      healthy individuals at variable risk for cardiovascular disease: A subanalysis of
      the EURO-EX trial.
AB  - INTRODUCTION: There has been a greater appreciation of several variables obtained
      by cardiopulmonary exercise testing (CPX). Exercise oscillatory ventilation (EOV)
      is a CPX pattern that has gained recognition as an ominous marker of poor
      prognosis in cardiac patients. The purpose of the present study is to
      characterize whether such an abnormal ventilatory pattern may also be detected in
      apparently healthy subjects and determine its clinical significance. METHODS: The
      study involved 510 subjects (mean age 60 +/- 14 years; 49% male) with a broad
      cardiovascular (CV) risk factor profile who underwent CPX. RESULTS: The
      population was divided into two groups according to the presence (17%) or absence
      of EOV. Subjects with EOV were significantly older and a higher percentage was
      female. Risk factor profile and medication use was significantly different
      between subgroups, indicating subjects with EOV had a worse CV risk factor
      profile and were prescribed CV-focused preventive medications at a significantly
      higher frequency. Subjects with EOV had comparatively poorer CPX performance and
      gas exchange phenotype. Multivariate binary logistic regression analysis found
      being female was the strongest predictor of EOV (odds ratio: 2.77, 95% confidence
      interval (CI): 1.66-4.61, p < 0.001). A diagnosis of diabetes (odds ratio: 2.40,
      95% CI: 1.34-4.15.2, p < 0.001) added significant value for predicting EOV and
      was retained in the regression. The likelihood for EOV for subjects who were
      female and diagnosed with diabetes was 3.71 (95% CI 1.88-7.30, p < 0.001).
      CONCLUSIONS: This is the first study to examine EOV prevalence and
      characterization in apparently healthy persons with results supporting an in
      depth definition of abnormal exercise phenotypes.

PMID- 25868604
TI  - Visual fluorescence detection of H2O2 and glucose based on "molecular beacon"
      hosted Hoechst dyes.
AB  - In this work, a label-free molecular beacon (MB)-like biosensor is designed for
      the determination of H2O2 and glucose based on the fluorescence regulation of
      Hoechst dyes hosted by the designed AT-rich single-stranded DNA (ssDNA), in which
      Hg(2+) and cysteine (Cys) act as activators. The designed AT-rich ssDNA (ATprobe)
      can be directed to form a hairpin with an Hg(2+)-induced T-Hg(2+)-T complex,
      which provides a medium for enhancing the fluorescence of Hoechst dyes
      significantly. On the other hand, Cys can effectively grab Hg(2+) from the T
      Hg(2+)-T complex by thiol-Hg(2+) interactions, destructing the hairpin and then
      switching the Hoechst dyes to the fluorescence "off" state. Combined with these
      properties, we have demonstrated its application for label-free fluorescence
      "turn on" detection of H2O2. The sensing mechanism is based on the specific
      reaction between H2O2 and Cys catalyzed by I(-), the resulting disulfide reverses
      the Cys-mediated fluorescence decrease of the MB-hosted Hoechst dyes. The
      approach achieves a low detection limit of 0.1 MUM for H2O2. Moreover, this
      method is further applied to the noninvasive detection of glucose in artificial
      saliva and urine samples, combining with glucose oxidase (GOx) for the oxidation
      of glucose and formation of H2O2. Compared to traditional methods, the proposed
      design is cost-effective, simple to prepare and manipulate without fluorescence
      labeling or chemical modification. 

PMID- 25868605
TI  - The pyruvate dehydrogenase complex in cancer: An old metabolic gatekeeper
      regulated by new pathways and pharmacological agents.
AB  - Cancer cells exhibit an altered metabolism which is characterized by a preference
      for aerobic glycolysis more than mitochondrial oxidation of pyruvate. This
      provides anabolic support and selective growth advantage for cancer cells.
      Recently, a new concept has arisen suggesting that these metabolic changes may be
      due, in part, to an attenuated mitochondrial function which results from the
      inhibition of the pyruvate dehydrogenase complex (PDC). This mitochondrial
      complex links glycolysis to the Krebs cycle and the current understanding of its
      regulation involves the cyclic phosphorylation and dephosphorylation by specific
      pyruvate dehydrogenase kinases (PDKs) and pyruvate dehydrogenase phosphatases
      (PDPs). 

PMID- 25868606
TI  - Comparison of Volumetric and Diametric Analysis in Endovascular Repair of
      Descending Thoracic Aortic Aneurysm.
AB  - OBJECTIVES: The aim was to evaluate computed tomography angiography (CTA)
      volumetric and diametric analysis after endovascular repair of descending
      thoracic aortic aneurysms (DTAAs) and its correlation with and applicability for
      clinical follow up. METHODS: Fifty-four consecutive endovascular repairs for DTAA
      were retrospectively evaluated from 2008 to 2014. All patients underwent pre
      operative CTA and at least one post-operative CTA at 6 months. Fifty-four pre
      operative and 137 post-operative CTAs were evaluated (using the Ziosoft 2
      software) to analyze the aneurysm and thrombus volume, the maximum aneurysm
      diameter, and their changes at the last follow up CTA (mean 30.5 months; range
      6.5-66.4 months). A statistical analysis was performed to assess the correlation
      between diameter and volume changes, as well as association with endoleaks. The
      cut off point to predict endoleaks was determined using a receiver operating
      characteristic (ROC) curve. The predictive accuracy of volume change versus
      diameter change for Type I endoleak was analyzed. RESULTS: The mean pre-operative
      aneurysm diameter, aneurysm volume, and thrombus volume were 56.7 +/- 11.7 mm,
      145.8 +/- 120.0 mL, and 48.8 +/- 54.8 mL, respectively. Within the observational
      period, a mean decrease of -27.9 +/- 30.5% in the aortic volume and -15.9 +/-
      15.4% in diameter was observed. Correlation between aneurysm diameter and volume
      changes was good (r = 0.854). Volume and diameter changes were significantly
      different between groups with and without endoleaks (volume change 16.9 +/- 38.8%
      vs. -35.6 +/- 23.1%, p < .001; diameter change 8.0 +/- 12.1% vs. -18.8 +/- 14.3%,
      p < .001). A pre-operative thrombus volume percentage of <11.3% and increase in
      aneurysm volume +11.6% were predictive factors for Type II and Type I endoleak,
      respectively. The accuracy of a >10% volume increase in predicting a Type I
      endoleak was higher (accuracy 96.3%, sensitivity 75%, and specificity 98%) than a
      >5 mm diameter increase (accuracy 92.6%, sensitivity 25%, and specificity 98%).
      CONCLUSIONS: CT volumetric analysis is a more reliable modality for predicting
      endoleaks after endovascular repair for DTAA than diameter analysis.

PMID- 25868607
TI  - New reporting standards are required to assess the impact of vascular
      intervention on patients with diabetic foot ulceration.

PMID- 25868608
TI  - Polarization control at spin-driven ferroelectric domain walls.
AB  - Unusual electronic states arise at ferroelectric domain walls due to the local
      symmetry reduction, strain gradients and electrostatics. This particularly
      applies to improper ferroelectrics, where the polarization is induced by a
      structural or magnetic order parameter. Because of the subordinate nature of the
      polarization, the rigid mechanical and electrostatic boundary conditions that
      constrain domain walls in proper ferroics are lifted. Here we show that spin
      driven ferroelectricity promotes the emergence of charged domain walls. This
      provides new degrees of flexibility for controlling domain-wall charges in a
      deterministic and reversible process. We create and position a domain wall by an
      electric field in Mn0.95Co0.05WO4. With a magnetic field we then rotate the
      polarization and convert neutral into charged domain walls, while its magnetic
      properties peg the wall to its location. Using atomistic Landau-Lifshitz-Gilbert
      simulations we quantify the polarization changes across the two wall types and
      highlight their general occurrence. 

PMID- 25868609
TI  - Human recombinant H2 relaxin induces AKT and GSK3beta phosphorylation and HTR
      8/SVneo cell proliferation.
AB  - Relaxin is essential for trophoblast development during pregnancy. Evidence shows
      that relaxin increases trophoblast cell migration capacity. Here, we show the
      effect of relaxin on protein kinase B (AKT) activation and glycogen synthase
      kinase 3-beta (GSK3beta) inactivation as well as on the proliferation of HTR
      8/SVneo cells, a model of human extravillous trophoblast (EVT). HTR-8/SVneo cells
      were treated with different doses of human recombinant (rH2) relaxin in serum
      deprived conditions and treated for increasing time with 1 ng/mL of rH2 relaxin.
      Western blot analysis was performed to detect pAKT, AKT, pGSK3beta, GSK3beta, and
      actin expression. Proliferation of HTR-8/SVneo cells was analyzed by MTS assay.
      rH2 relaxin treatment increased the ratio of pAKT/AKT, pGSK3beta/GSK3beta, and
      proliferation in HTR-8/SVneo cells. Furthermore, AKT and GSK3beta activation by
      rH2 relaxin was inhibited by a phosphoinositide 3-kinase (PI3K) inhibitor. This
      study suggests that rH2 relaxin induces AKT and GSK3beta phosphorylation as well
      as proliferation in HTR-8/SVneo cells. 

PMID- 25868610
TI  - Attention Deficit/Hyperactivity Disorder (ADHD): age related change of completion
      time and error rates of Stroop test.
AB  - BACKGROUND: Attention Deficit/Hyperactivity Disorder (ADHD) is a common
      neurobehavioral problem in children throughout the world. The Stroop test has
      been widely used for the evaluation of ADHD symptoms. However, the age-related
      change of the Stroop test results has not been fully clarified until now.
      METHODS: Sixty-five ADHD and 70 age-matched control children aged 6-13 years were
      enrolled in this study. ADHD was diagnosed based on DSM-IV criteria. We examined
      the completion time and error rates of the Congruent Stroop test (CST) and
      Incongruent Stroop test (IST) in ADHD and control children. RESULTS: No
      significant difference was observed in the completion time for CST or IST between
      the ADHD and control children at 6-9 years old. However, ADHD children at 10-13
      years old showed significantly delayed completion time for the CST and IST
      compared with controls of the same age. As for the error rates of the CST and
      IST, ADHD and control children at 6-9 years old showed no difference. However,
      error rates of CST and IST in the ADHD children at 10-13 years were significantly
      higher than those of control of the same age. CONCLUSIONS: Age may influence the
      results of Stroop test in ADHD children. For the ages of 10-13 years old, the
      Stroop test clearly separates ADHD children from control children, suggesting
      that it may be a useful screening tool for ADHD among preadolescent children.

PMID- 25868611
TI  - The NS5A protein of hepatitis C virus transcriptionally upregulates the AGR3 gene
      expression.
AB  - The non-structural protein 5A (NS5A) of hepatitis C virus (HCV) is a
      multifunctional protein involved in the HCV lifecycle and pathogenesis. The
      precise molecular mechanisms of NS5A-mediated pathogenesis still remain to be
      clarified. In this study, we performed cDNA microarray analysis on NS5A
      expressing HEK293 cells and the non-expressing control to screen the possible
      cellular genes dysregulated by NS5A. Subsequent quantitative real time PCR (qRT
      PCR) analysis on NS5A-expressing cells and the control confirmed that NS5A
      upregulated the anterior gradient homolog 3 (AGR3) mRNA expression. The domain
      III of NS5A was responsible for the activation of AGR3 gene expression. AGR3 mRNA
      expression levels were upregulated also in Huh7.5 cells harboring a full-genome
      HCV-1b RNA replicon (FGR) and in those infected with HCV-2a. Moreover, AGR3
      promoter activity was activated in NS5A-expressing cells, FGR-harboring cells and
      HCV-infected cells. Taken together, our present results suggest that HCV NS5A
      transcriptionally activates the cancer-associated AGR3 gene. This may be a novel
      mechanism of HCV-mediated pathogenesis, especially hepatocarcinogenesis. 

PMID- 25868612
TI  - The augmented representation of the cost-effectiveness acceptability curve for
      economic evaluation of health technology.
AB  - New schemes on the cost-effectiveness acceptability curve (CEAC) were developed,
      which can make the CEAC augmented to be more informative regarding the types of
      acceptance and statistical inference. Theoretical approaches have been undertaken
      to address two questions: 1) how the area under the curve (AUC) can be zoned by
      different types of acceptance displayed on the incremental cost-effectiveness
      plane, and 2) how the accepted dataset of incremental cost-effectiveness ratios
      (ICERs), which are generated by simulation runs, can be statistically associated
      with a threshold of ICER for acceptance. To address the first question, the AUC
      of a typically sigmoid-shaped CEAC was divided into three zones according to the
      three segmentations of the scattered plots accepted at South-east, North-east and
      South-west quadrants on the incremental cost-effectiveness plane. A solution for
      the second question was "a new CEAC of the mean" (mCEAC), which is defined by
      plotting a pair of the mean and its occurrence probability of ICER accepted at
      North-east quadrant on the incremental cost-effectiveness plane. All those
      schemes were graphically illustrated based on hypothetical examples using the
      bootstrapping simulation. Our new schemes on CEAC will provide decision makers
      with useful information on cost-effectiveness assessment beyond the standard
      presentation of CEAC. 

PMID- 25868614
TI  - Antihyperglucolipidaemic and anticarbonyl stress properties in green, yellow and
      red sweet bell peppers (Capsicum annuum L.).
AB  - Effect of aqueous methanol extract of different colour sweet bell peppers
      (Capsicum annuum L.) on parameters of diabesity and carbonyl stress was analysed
      in vitro. Yellow pepper displayed significantly (p < 0.001) higher intestinal
      alpha-glucosidase inhibitory activity than green and red pepper. Porcine
      pancreatic lipase inhibitory activity was significantly (p < 0.01) high in yellow
      and red pepper than in green pepper. Green and red pepper inhibited vesperlysine
      type advanced glycation end products (AGEs) more potently than yellow pepper;
      however, pentosidine-type AGEs were similarly inhibited by all three peppers.
      Yellow and red pepper inhibited lipid peroxidation more potently (p < 0.01) than
      green pepper. Total polyphenol content and free radicals scavenging activities in
      yellow and red bell peppers were higher than in green pepper. Total flavonoid
      content was high in green pepper than that present in yellow and red peppers.
      Green pepper displayed presence of proanthocyanins; however, oligomeric
      anthocyanins were detected in yellow and red peppers.

PMID- 25868613
TI  - Nuclear expression of p65 (RelA) in patients receiving post-operative
      radiotherapy for locally advanced squamous cell carcinoma of the head and neck.
AB  - BACKGROUND: This study investigated the prognostic role of nuclear expression of
      p65 in patients with locally advanced squamous cell carcinoma of the head and
      neck (SCCHN) receiving post-operative radio(chemo)therapy. METHODS: Nuclear p65
      expression (H-score <=50 versus >50) plus twelve characteristics were analyzed in
      151 patients for overall survival (OS), metastases-free survival (MFS) and loco
      regional control (LRC). Additional characteristics included age, gender,
      Karnofsky performance score (KPS), pre-radiotherapy hemoglobin levels, tumor
      site, histological grading, human papilloma virus (HPV)-status, T-classification,
      N-classification, American Joint Committee on Cancer (AJCC)-stage, extent of
      resection and concurrent chemotherapy. Univariate analyses were performed with
      Kaplan-Meier method and log-rank test, multivariate analyses with Cox
      proportional hazards model. RESULTS: On univariate analyses, p65-expression had a
      significant impact on OS (p < 0.001) and LRC (p < 0.001) but not on MFS (p =
      0.29). On multivariate analysis, KPS >=80 (risk ratio [RR] 2.23; p = 0.012), HPV
      positivity (RR 5.83; p = 0.020), T1-T2 (RR 1.38; p = 0.048), N0-N2a (RR 2.72; p =
      0.005) and complete resection (RR 2.02; p = 0.049) were positively associated
      with OS; p65-negativity achieved borderline significance (RR 3.02; p = 0.052).
      Better MFS was associated with KPS >=80 (RR 2.49; p = 0.015), T1-T2 (RR: 1.74; p
      = 0.005), N0-N2a (RR: 6.22; p < 0.001) and complete resection (RR 3.43; p =
      0.003). Positive associations with LRC were found for p65-negativity (RR 5.06; p
      = 0.008), T1-T2 (RR: 1.49; p = 0.022), N0-N2a (RR: 2.97; p = 0.004) and favorable
      tumor site (RR 1.28; p = 0.025). CONCLUSIONS: P65-negativity was significantly
      associated with improved LRC and achieved borderline significance with respect to
      improved OS. Thus, p65-expression may be an additional target for novel agents in
      the treatment of locally advanced SCCHN.

PMID- 25868615
TI  - Effects of dietary supplementation with fermented ginkgo leaves on antioxidant
      capacity, intestinal morphology and microbial ecology in broiler chicks.
AB  - 1. The purpose of this study was to evaluate the effects of supplementing diets
      with three types of fermented Ginkgo-leaves (FGL) on growth, antioxidant
      capacity, intestinal morphology and microbial ecology in broiler chicks. 2. A
      total of 300 d-old broilers were randomly allocated to 4 dietary treatments with
      6 replications of 10 birds each. Birds were fed on basal diets (Control) or basal
      diets supplemented with 0.5% FGL with Candida utilis (CF group), Aspergillus
      niger (AF group) or their combined fermentation (CAF group), respectively, for a
      42 d feeding trial. 3. AF and CAF supplementation improved body weight gain (BWG)
      (22-42 d) and feed conversion ratio (22-42 d and 1-42 d). Concentrations of serum
      alpha-tocopherol in CAF group, as well as hepatic alpha-tocopherol in the three
      FGL groups were increased, while hepatic reactive oxygen species (ROS) levels
      were greatly decreased in group AF and CAF. Chickens in AF and CAF groups had
      decreased hepatic protein carbonyls and malondialdehyde (MDA), as well as jejunal
      and ileal protein carbonyls. The total superoxide dismutase (T-SOD) activities
      and glutathione (GSH) of both jejunum and ileum of the CAF group were higher than
      the other groups. 4. Duodenal and jejunal villous height of birds fed on the AF
      and CAF diets were increased, while jejunal crypt depth (CD) was decreased.
      Furthermore, birds fed on AF and CAF supplemented diets had increased ileal
      lactobacilli populations. Decreased ileal and caecal Escherichia coli and
      Salmonellas populations was found for the birds fed on CAF supplemented diets. 5.
      The present study may indicate that the improved feed efficiency and intestinal
      functions in the group supplemented with AF and CAF are directly connected with
      the improved antioxidant capacity and intestinal microbial ecology.

PMID- 25868616
TI  - Protective effects of caffeoylxanthiazonoside isolated from fruits of Xanthium
      strumarium on sepsis mice.
AB  - CONTEXT: The fruit of Xanthium strumarium L. (Asteraceae) has been used for the
      treatment of various inflammatory diseases. OBJECTIVE: This study investigates
      the protective effect of caffeoylxanthiazonoside (CYXD) isolated from fruits of
      X. strumarium on sepsis mice in vitro and in vivo. MATERIALS AND METHODS: Cecal
      ligation and puncture (CLP) operation was used to establish the sepsis mice
      model, and sham mice were also performed. CYXD was administered by
      intraperitoneal injection (10, 20, and 40 mg/kg/d), then the survival rate was
      measured in 96 h. Additionally, sepsis mice were induced by injection LPS (2
      mg/kg); CYXD was administered by intraperitoneal injection (10, 20, and 40
      mg/kg/d), then mice were sacrificed, and serum levels of TNF-alpha and IL-6 were
      determined by ELISA assay. Furthermore, the ability of CYXD to neutralize LPS was
      measured by using the LAL test, and expressions of TNF-alpha, IL-6 were
      determined by using real-time fluorogenic PCR. RESULTS: Results indicated that
      CYXD significantly elevated survival rates of sepsis mice induced by CLP (p <
      0.05) with survival rates of 35%, 45%, and 65%. Furthermore, the LPS level was
      decreased obviously by CYXD (1, 2, and 4 mg/L) (p < 0.05). Additionally, CYXD
      (10, 20, and 40 mg/kg) can not only significantly decrease TNF-alpha and IL-6
      levels induced by LPS in mice's serum (p < 0.05), but also inhibit mRNA
      expressions of TNF-alpha and IL-6 induced by LPS in RAW 264.7 cells at doses of
      20, 40, and 80 MUg/mL (p < 0.05). CONCLUSION: Our study demonstrated that CYXD
      has significant protective effects on sepsis mice.

PMID- 25868617
TI  - Antiallergic effect of piperine on ovalbumin-induced allergic rhinitis in mice.
AB  - CONTEXT: Allergic rhinitis (AR) is a global health problem that affects a large
      number of population. Piperine (PIP) has been reported to exhibit anti
      inflammatory, anti-histaminic, and immunomodulatory activities; however, its
      antiallergic profile has not been studied. OBJECTIVE: The objective of the study
      was to investigate the antiallergic potential of PIP in ova-albumin (OVA)-induced
      AR, mast cell degranulation (MSD), and OVA-induced paw edema. MATERIALS AND
      METHODS: Mice were sensitized with OVA alternately on 1, 3, 5, 7, 9, 11, and 13th
      day. They were treated with either vehicle, PIP (10, 20, and 40 mg/kg, p.o.), or
      montelukast (10 mg/kg, p.o.) from the 14th to 20th day. On the 21st day,
      intranasal (OVA: 5% ul) challenge was done. Animals were evaluated for
      physiological parameters, biochemical parameters, spleen weight, expression of
      interleukins (IL-6 and IL-1beta), and immunoglobin-E (IgE). Histopathology of
      nasal mucosa, lungs, and spleen was carried out. MSD and paw edema studies were
      made to understand the mechanism of action. RESULTS: PIP (10, 20, and 40 mg/kg,
      p.o.) showed a significant dose-dependent protection with respect to nasal
      rubbing, redness of nose, and sneezing (p < 0.001) following nasal challenge. PIP
      dose dependently reduced histamine, NO concentration (p < 0.001), as well as
      reduced expression of IL-6, IL-1beta, and IgE (p < 0.001) as compared with the
      control group. Histopathology showed inhibition of infiltration of eosinophils
      and hyperplasia. It dose dependently reduced MSD and paw edema (p < 0.001).
      DISCUSSION AND CONCLUSION: PIP acts by mast cell-stabilizing activity, exhibits
      immunomodulatory and anti-inflammatory activity, thereby providing an effective
      treatment for AR.

PMID- 25868618
TI  - Endophytic bacteria from Pinellia ternata, a new source of purine alkaloids and
      bacterial manure.
AB  - CONTEXT: Pinellia ternata (Thunb.) Berit., a perennial herb belonging to Araceae,
      is one of the few medicinal plants to produce purine alkaloids. It is speculated
      that endophytic bacteria from P. ternata may produce guanosine or inosine.
      However, there is no report about endophytic bacteria in P. ternata. OBJECTIVE:
      In this study, endophytic bacteria were isolated from P. ternata and examined for
      the first time. This study finds a novel way to increase the yield of P. ternata
      herb, and to provide some new alkaloid producers. MATERIALS AND METHODS: Plant
      material includes leaves, tubers, and roots of cultivated and wild P. ternata.
      The dilutions were smeared onto beef extract-peptone medium and cultured at 28 
      degrees C in darkness for 48-72 h. Co-culture treatments were prepared by
      inoculating 100 mL liquid 1/2 MS medium with bacterial culture broth at
      concentrations of 0 (control), 0.5%, and 1.5% (v/v). RESULTS: Of the 34
      endophytic bacterial colonies isolated from P. ternata leaves, roots, and tubers,
      five strains were able to produce purine alkaloids. Results from 16s rDNA
      sequence analysis indicated that the bacteria belonged to Bacillus cereus,
      Aranicola proteolyticus, Serratia liquefaciens, Bacillus thuringiensis, and
      Bacillus licheniformis. Co-culture with living Serratia liquefaciens cells
      increased PLB growth by 58-71%. Co-culture with living Bacillus licheniformis
      cells increased PLB growth by 4-11%. CONCLUSION: This study provides a novel way
      for improving the yield of P. ternata herb, and for the production of purine
      alkaloids by the fermentation industry.

PMID- 25868619
TI  - Angiotensin-converting enzyme (ACE) inhibitory potential of standardized Mucuna
      pruriens seed extract.
AB  - CONTEXT: Mucuna pruriens Linn. (Fabaceae) is a tropical legume, traditionally
      used for controlling blood pressure. Inhibition of angiotensin-converting enzyme
      (ACE) is one of the successful strategies for controlling hypertension.
      OBJECTIVE: The present study evaluated the ACE inhibition potential of the
      standardized extract of M. pruriens seeds. MATERIALS AND METHODS: Standardization
      of the extract and its fractions were carried out by RP-HPLC method [methanol and
      1% v/v acetic acid in water (5:95 v/v)] using levodopa as a marker. The ACE
      inhibition activity of the extract and fractions was evaluated at different
      concentrations (20, 40, 60, 80, and 100 ug/mL) using the HPLC-DAD and the UV
      spectrophotometric method. The liberation of hippuric acid (HA) from hippuryl-L
      histidyl-L-leucine (HHL) was estimated in the spectrophotometric method and RP
      HPLC assay at 228 nm. RESULTS: Methanol extract and aqueous fraction showed a
      maximum activity with IC50 values of 38.44 +/- 0.90 and 57.07 +/- 2.90 ug/mL (RP
      HPLC), and 52.68 +/- 2.02 and 67.65 +/- 2.40 ug/mL (spectrophotometry),
      respectively. DISCUSSION: The study revealed that the aqueous extract contains
      the highest amount of levodopa. Eventually the methanol extract showed highest
      ACE inhibition activity except levodopa alone. It was further observed that the
      inhibition was altered with respect to the change in the content of levodopa in
      the extract. Thus, it can be assumed that levodopa may be responsible for the ACE
      inhibition activity of M. pruriens seeds. CONCLUSION: It can be concluded that M.
      pruriens seed is a potential ACE inhibitor can be explored further as an
      effective antihypertensive agent.

PMID- 25868620
TI  - Protective effects of the standardized extract of Zingiber officinale on
      myocardium against isoproterenol-induced biochemical and histopathological
      alterations in rats.
AB  - CONTEXT: Ginger [Zingiber officinale Roscoe. (Zingiberaceae)] has been
      universally used as a spice as well as for its health benefits. OBJECTIVE: The
      present study evaluates the protective effect of the standardized extract of
      ginger against isoproterenol (ISO)-induced myocardial infarction (MI) in rats.
      MATERIALS AND METHODS: Wistar rats were pretreated orally with three doses of
      standardized ginger extract (100, 200, and 400 mg/kg of body weight) or
      propranolol (5 mg/mL) for 28 d prior to ISO (85 mg/kg) induced MI in two doses on
      days 29 and 30. The rats were sacrificed 48 h after the first induction; serum
      and hearts were collected for biochemical and histopathological analysis.
      RESULTS: Gingerols and shogaols were identified and quantitatively analyzed in
      the extracts using validated reversed phase HPLC methods. Pretreatment with
      ginger extract at 400 mg/kg showed a significant decrease (p < 0.05) in all the
      cardiac enzyme activities, i.e., cardiac troponin I (cTnI) (0.57 ng/mL), creatine
      kinase MB isoenzyme (CK-MB) (10.34 pg/mL), lactate dehydrogenase (LDH) (115.22
      U/L), alanine transaminase (ALT) (15.79 U/L), and aspartate transaminase (AST)
      (46.72 U/L) when compared with ISO-control rats. There were significant rises (p
      < 0.05) in the activity of glutathione peroxide (GPx) (53.16 U/L), catalase (CAT)
      (210.41 U/L), and superoxide dismutase (SOD) (280.89 U/mL) of the pretreated rats
      when compared with the ISO-control. Histopathological examination showed an
      improvement in membrane cell integrity in pretreated rats compared with untreated
      rats. CONCLUSION: The ethanol extract of ginger exhibited cardioprotective
      potential in treating myocardial injury following ISO administration.

PMID- 25868621
TI  - Anti-HIV-1 integrase activity and molecular docking of compounds from Albizia
      procera bark.
AB  - CONTEXT: Albizia procera (Roxb.) Benth. (Mimosaceae) has been traditionally used
      in Thai longevity preparations. Thus, searching for HIV-1 integrase (HIV-1 IN)
      agents from natural sources is of interest. OBJECTIVE: The objective of this
      study is to examine the inhibitory activity against HIV-1 IN of compounds
      isolated from the stem bark of Albizia procera. MATERIALS AND METHODS: The EtOH
      extract and isolated compounds of Albizia procera bark were examined for anti-HIV
      1 IN activity at various concentrations (10-100 ug/mL and 10-100 uM) using the
      multiplate integration assay and molecular docking. RESULTS AND DISCUSSIONS: The
      results showed that the ethanol extract had good anti-HIV-1 IN activity with an
      IC50 value of 19.5 ug/mL, whereas ethyl acetate fraction exhibited the most
      potent with an IC50 value of 19.1 ug/mL, followed by water fraction (IC50 value =
      21.3 ug/mL), hexane and chloroform fractions (IC50 value > 100 ug/mL),
      respectively. From bioassay-guided isolation, the ethyl acetate fraction was
      further separated to give two compounds which are (+)-catechin (1) and
      protocatechuic acid (2), respectively. Of the tested samples, (+)-catechin (1)
      exhibited appreciable activity against HIV-1 IN with an IC50 value of 46.3 uM,
      whereas protocatechuic acid (2) showed mild activity with 46.0% inhibition at
      concentration of 100 uM. (+)-Catechin (1) could interact with Thr66, Gly148, and
      Glu152 in the core domain of IN enzyme, whereas protocatechuic acid (2) could
      bind with Thr66, His67, Glu152, Asn155, and Lys159. This is the first report on
      anti-HIV-1 IN activity of Albizia procera bark. These results may suggest that
      Albizia procera bark has potential as anti-HIV-1 IN agent.

PMID- 25868622
TI  - Stem bark and flower extracts of Vismia cauliflora are highly effective
      antioxidants to human blood cells by preventing oxidative burst in neutrophils
      and oxidative damage in erythrocytes.
AB  - CONTEXT: Vismia cauliflora A.C.Sm. [Hypericaceae (Clusiaceae)] is an Amazonian
      plant traditionally used by indigenous population to treat dermatosis and
      inflammatory processes of the skin. Previous research on V. cauliflora extracts
      suggests its potential to neutralize cellular oxidative damages related to the
      production of reactive oxygen and nitrogen species. OBJECTIVE: To determine the
      activity of stem bark and flower extracts of V. cauliflora on the modulation of
      oxidative burst in human neutrophils, as well as its potential to inhibit
      oxidative damage in human erythrocytes. MATERIALS AND METHODS: The modulation of
      neutrophil's oxidative burst by the ethanolic extracts (0.3-1000 ug/mL) was
      determined by the oxidation of specific probes by reactive species. Additionally,
      the potential of these extracts to inhibit oxidative damage in human erythrocytes
      was evaluated by monitoring its biomarkers of oxidative stress. RESULTS: Vismia
      cauliflora extracts presented remarkable capacity to prevent the oxidative burst
      in activated human neutrophils (IC50 < 15 ug/mL). However, the maximum percentage
      of inhibition achieved against hydrogen peroxide was 45%. Concerning the
      oxidative damage in human erythrocytes, the extracts were able to minimize the
      tert-butyl hydroperoxide-induced hemoglobin oxidation and lipid peroxidation in a
      very low concentration range (2.7-18 MUg/mL). Furthermore, only stem bark extract
      (100 ug/mL) was able to inhibit the depletion of glutathione (13%). DISCUSSION
      AND CONCLUSION: These results reinforce the therapeutic potential of stem bark
      and flower extracts of V. cauliflora to heal topical skin disease, namely in the
      treatment of neutrophil-related dermatosis and skin conditions related to
      oxidative stress, including skin aging.

PMID- 25868623
TI  - Interactive Feature Space Explorer(c) for multi-modal magnetic resonance imaging.
AB  - Wider information content of multi-modal biomedical imaging is advantageous for
      detection, diagnosis and prognosis of various pathologies. However, the necessity
      to evaluate a large number images might hinder these advantages and reduce the
      efficiency. Herein, a new computer aided approach based on the utilization of
      feature space (FS) with reduced reliance on multiple image evaluations is
      proposed for research and routine clinical use. The method introduces the
      physician experience into the discovery process of FS biomarkers for addressing
      biological complexity, e.g., disease heterogeneity. This, in turn, elucidates
      relevant biophysical information which would not be available when automated
      algorithms are utilized. Accordingly, the prototype platform was designed and
      built for interactively investigating the features and their corresponding
      anatomic loci in order to identify pathologic FS regions. While the platform
      might be potentially beneficial in decision support generally and specifically
      for evaluating outlier cases, it is also potentially suitable for accurate ground
      truth determination in FS for algorithm development. Initial assessments
      conducted on two different pathologies from two different institutions provided
      valuable biophysical perspective. Investigations of the prostate magnetic
      resonance imaging data resulted in locating a potential aggressiveness biomarker
      in prostate cancer. Preliminary findings on renal cell carcinoma imaging data
      demonstrated potential for characterization of disease subtypes in the FS. 

PMID- 25868624
TI  - Efficient production and evaluation of lignocellulolytic enzymes using a
      constitutive protein expression system in Penicillium oxalicum.
AB  - Native lignocellulolytic enzyme systems secreted by filamentous fungi can be
      further optimized by protein engineering or supplementation of exogenous enzyme
      components. We developed a protein production and evaluation system in cellulase
      producing fungus Penicillium oxalicum. First, by deleting the major amylase gene
      amy15A, a strain Delta15A producing few extracellular proteins on starch was
      constructed. Then, three lignocellulolytic enzymes (BGL4, Xyn10B, and Cel12A)
      with originally low expression levels were successfully expressed with selected
      constitutive promoters in strain Delta15A. BGL4 and Cel12A overexpression
      resulted in increased specific filter paper activity (FPA), while the
      overexpression of Xyn10B improved volumetric FPA but not specific FPA. By
      switching the culture medium, this platform is convenient to produce originally
      low-expressed lignocellulolytic enzymes in relatively high purities on starch and
      to evaluate the effect of their supplementation on the performance of a complex
      cellulase system on cellulose. 

PMID- 25868625
TI  - Spondylodiscitis due to Rhizobium radiobacter.

PMID- 25868626
TI  - Molecular characterization and mRNA expression of HIF-prolyl hydroxylase-2 (phd2)
      in hypoxia-sensing pathways from Megalobrama amblycephala.
AB  - HIF-prolyl-hydroxylase-2 (Phd2), a member of the iron (II) and 2-oxoglutarate
      dependent dioxygenase family, is one of the key enzymes in hypoxia-sensing
      pathways. In this study, the phd2 cDNA sequence (1231bp), including an open
      reading frame (ORF) and encoding 358 amino acid residues was identified in
      Megalobrama amblycephala (Wuchang bream). The predicted Phd2 protein contained
      three conserved domains, MYND type zinc finger domain with critical regulatory
      activity, Fe(2+)-dependent 2OG-Fe (II) oxygenase superfamily domain with prolyl
      hydroxylase function, and P4Hc (prolyl 4-hydroxylase alpha subunit homologues)
      domain for catalyzing proline hydroxylation. The real-time PCR results showed
      that phd2 mRNA was ubiquitously expressed in all detected tissues with higher
      levels in the peripheral blood, heart and brain, and all embryogenesis stages,
      especially in mid-blastula stage. In larvae M. amblycephala, the expression trend
      of the phd2 and hypoxia-inducible factor 1 alpha (hif-1alpha) mRNA was opposite
      during hypoxia with an increase (hypoxia for 4h) and then decrease (hypoxia for
      12h) for phd2. Whereas in adult fish, the phd2 mRNA appeared a transient increase
      under hypoxia for 4h (DO: 3.46+/-0.59 mg/L), and dramatically reduced with
      further hypoxia exposure to 12h in the peripheral blood, muscle, head kidney,
      liver and brain, but showed an opposite expression trend in the heart and gill.
      The hif-1alpha expression was contrary with phd2 in the peripheral blood, while
      it gradually decreased in the heart, but increased in the liver with continuous
      hypoxia treatment. Additionally, hif-1alpha also showed lower mRNA levels than
      phd2 in all detected tissues under normoxia and hypoxia conditions. 

PMID- 25868627
TI  - Cloning, characterization and analysis of the 5' regulatory region of zebrafish
      xpd gene.
AB  - The gene XPD/ERCC2 encodes an ATP-dependent 5'-3' helicase of 760 amino acids.
      There are few transcription factors known to be involved in the regulation of
      XPD, and these include the hypoxia-inducible factor-1alpha (HIF-1alpha), p53,
      hepatitis B virus x protein (HBx) and specificity protein 1 (Sp1). To identify
      functional elements of xpd gene in fish we employed a comparative genomic
      approach. In our in silico attempt to identify cis-regulatory transcription
      factor binding sites (TFBSs) conserved among the xpd promoter sequences from five
      available fish species, we verified that in some cases the spatial disposition of
      the putative TFBSs was not maintained, but they were present in all the
      sequences, allowing the prediction of conserved regulatory elements within the
      promoter sequences analysed. We also investigated the transcriptional regulation
      of the zebrafish xpd gene. Our in vitro transient transfection-reporter analysis
      identified a region in the zebrafish xpd gene responsible for xpd regulation,
      along with regulatory regions that inhibit the activity of this promoter in
      somatic cells. Moreover, we found two p53 binding sites in the xpd promoter and
      upon co-transfection assays we observed a repression due to p53. This provides
      the first identification and characterization of promoter regions that regulate
      the transcription of the zebrafish xpd gene, and offers insights into the
      regulation of this gene by p53. Together, these studies further support the
      utility of comparative genomics to uncover gene regulatory sequences based on
      evolutionary conservation and provide the basic information to explore and better
      understand the regulation and expression of XPD. 

PMID- 25868628
TI  - The study of fkbp and ubiquitin reveals interesting aspects of Artemia stress
      history.
AB  - Research on stress responses in animals has increased greatly during the last
      decades. Though most studies focus on the cellular and molecular bases of the
      stress response mechanisms, the ecological and evolutionary aspects of stress
      responses gain more and more interest. Here, we use species and parthenogenetic
      strains of the genus Artemia, an extremophile model organism, to study, for the
      first time, a protein well known for its chaperone activity and its involvement
      in stress responses. More specifically, transcription and protein accumulation of
      an FK506-Binding Protein (FKBP) homologue were investigated under heat and salt
      stresses. Additionally, the mRNA levels of ubiquitin, a heat-inducible protein
      related to the proteasomal pathway, were quantitated under these conditions.
      Biochemical and phylogenetic analyses showed that the studied FKBP orthologue is
      a typical representative of the family that clusters with other crustacean
      sequences. The expression was increased in both fkbp and ubiquitin genes after
      salt and heat stresses. However, our results in combination with the fact that
      Artemia species and parthenogenetic strains, selected for this study, exhibit
      different heat or salt tolerance provide useful hints about the evolutionary
      significance of FKBP and ubiquitin. Regarding FKBP, mRNA expression and protein
      accumulation seem to depend on the environmental conditions and the evolutionary
      history of each Artemia population while ubiquitin has a clear and more conserved
      role under heat shock. 

PMID- 25868629
TI  - A Trial of Rectal Indomethacin to Prevent Post-ERCP Pancreatitis in Patients with
      Suspected Type 3 Sphincter of Oddi Dysfunction.
AB  - BACKGROUND AND AIM: Recent data have suggested that rectal indomethacin can also
      reduce the incidence of post-endoscopic retrograde cholangiopancreatography
      pancreatitis (PEP). The aim of this study was to determine whether prophylactic
      rectal indomethacin with PD stenting would reduce the incidence and severity of
      PEP compared to PD stenting alone in patients undergoing manometry for suspected
      SOD type 3. PATIENTS AND METHODS: A retrospective review of consecutive patients
      who underwent an ERCP with manometry for suspected SOD type 3 was performed.
      Patients were divided into two groups: (a) those who received a prophylactic PD
      stent (n = 285) and (b) those who received a prophylactic PD stent and a single
      dose of 100-mg indomethacin suppositories after ERCP (n = 57). The rate of PEP
      was compared between the two groups. RESULTS: The two patient groups were similar
      with regard to patient and procedure risk factors for PEP. Post-ERCP pancreatitis
      developed in 22 % patients. There was no significant difference in the incidence
      of PEP in the PD stent group compared to the PD stent and indomethacin group (23
      vs. 18 %, respectively; p = 0.39). Moderate-to-severe pancreatitis developed in
      21 (7 %) patients in the PD stent group compared to 5 (9 %) patients in the PD
      stent and indomethacin group (p = 0.78). Among patients with PEP, the median
      length of hospital stay was not significantly longer in the PD stent group
      compared to the PD stent and indomethacin group (6 vs. 4 days, respectively; p =
      0.11). CONCLUSIONS: In patients with suspected SOD type 3, prophylactic rectally
      administered indomethacin with PD stenting was not observed to affect the
      incidence or severity of post-ERCP pancreatitis when compared to PD stenting
      alone.

PMID- 25868630
TI  - Clinical Features and Colonic Motor Disturbances in Chronic Megacolon in Adults.
AB  - BACKGROUND: Chronic megacolon is a rare disease of the colonic motor function
      characterized by a permanent increase in colonic diameter. METHODS: We reviewed
      electronic medical records of all patients diagnosed with chronic megacolon from
      1999 to 2014 at Mayo Clinic. Our aim was to summarize clinical and motility
      features, including colonic compliance and tone measured by colonic barostat
      controlled 10-cm-long infinitely compliant balloon. Colonic compliance curves
      were compared to healthy control (40) and disease (47) control groups. RESULTS:
      Among 24 identified patients, the mean maximal colonic diameter on abdominal
      radiograph was 12.7 +/- 0.8 cm. The cause of megacolon was idiopathic in 16 of 24
      and secondary in 8 of 24. A relatively high prevalence (10/24) of comorbid pelvic
      floor dyssynergia was identified. At the time of this report, 16 patients had
      undergone colectomy. In general, megacolon presented high fasting colonic volume
      at relatively low pressures (16-20 mmHg), suggesting high colonic compliance;
      similarly, volumes at operating pressures that ensured apposition of the balloon
      to the colonic wall suggested low colonic tone. Median balloon volume at 44 mmHg
      distension was 584 mL (IQR 556.5-600) in patients with megacolon compared to 251
      mL (212-281) in healthy, 240 mL (207-286) in functional constipation, and 241 mL
      (210.8-277.5) in diarrhea-predominant irritable bowel syndrome controls. Colon's
      tonic response to feeding was generally intact, and there was frequently
      maintained phasic contractile response to feeding. CONCLUSIONS: Chronic megacolon
      is a severe colonic dysmotility, manifesting radiologically with increased
      colonic diameter; it can be proven by measuring colonic compliance and typically
      requires colectomy because of failed medical therapy.

PMID- 25868631
TI  - No Distal Migration in Unfixed Versus Fixed Cell Structure Covered Self-Expanding
      Metal Stents for Treatment of Benign Biliary Disease.
AB  - BACKGROUND: Fully covered self-expandable metal stents (FCSEMS) are increasingly
      used for treatment of benign common bile duct (CBD) stricture or leakage, but
      dislodgement of FCSEMS is frequent. AIMS: To compare dislocation rate and
      clinical outcome of a standard fixed cell structure FCSEMS (S-FCSEMS) to a novel
      FCSEMS with an unfixed cell structure (N-FCSEMS). METHODS: We performed a
      retrospective analysis of all patients with FCSEMS insertion for benign biliary
      disease at our Hospital from 03/2008 to 03/2014. Both stent types N-FCSEMS and S
      FCSEMS were applied as available unrelated to the indication. RESULTS: Twenty
      nine patients (S-FCSEMS: 18, N-FCSEMS: 11) were included. Stent placement was
      technically successful in 28/29 (96.6 %) patients; stent removal was successful
      in 26/27 (96.2 %). Two patients with N-FCSEMS were excluded due to unsuccessful
      placement and withdrawal of consent for stent removal, respectively. Stent
      migration into the duodenum (distal migration) was observed in 9/18 (50 %) in the
      S-FCSEMS group compared to 0/9 in the N-FCSEMS (p < 0.005). FCSEMS migration into
      the CBD (proximal migration) was found in 2/18 (11 %, S-FCSEMS) versus 2/9 (22 %,
      N-FCSEMS, p = 0.514). A foreshortening of the N-FCSEMS occurred in 3/9 patients
      (33 %) compared to 0/18 S-FCSEMS (p = 0.08). Clinical resolution of the treated
      CBD-disease was observed in 5/9 (56 %, N-FCSEMS) versus 12/18 (67 %, S-FCSEMS) at
      the time of stent removal (p = 0.604) and in 0/9 and 10/18 (56 %) cases during
      follow-up, respectively (p < 0.005). CONCLUSION: An unfixed cell structure of
      FCSEMS seems to prevent distal migration, but proximal migration still occurs and
      foreshortening of the N-FCSEMS constrains clinical outcome.

PMID- 25868632
TI  - Rendezvous EndoSeel Technique for Non-operative Closure of Anastomotic Leak After
      Ileoanal Pouch Operation.

PMID- 25868634
TI  - Comparison of Narrow Band Imaging and Fujinon Intelligent Color Enhancement in
      Predicting Small Colorectal Polyp Histology.
AB  - BACKGROUND: There are limited data on the performance of narrow band imaging
      (NBI) and Fujinon intelligent color enhancement (FICE) for differentiating polyp
      histologies. AIMS: The aim of this study was to compare the diagnostic
      performances of NBI and FICE in differentiating neoplastic from non-neoplastic
      colorectal polyps <10 mm during screening colonoscopy. METHODS: A total of 955
      average-risk adults undergoing screening colonoscopies were randomly allocated to
      NBI or FICE groups. Four board-certified staff endoscopists without prior
      experience using NBI or FICE participated. The main outcomes of this study were
      overall accuracy, sensitivity, and specificity of FICE and NBI in identifying
      neoplastic polyps. RESULTS: There was no significant difference in the number of
      subjects with adenoma between the NBI (143/475, 30.1 %) and FICE groups (139/480,
      29.0 %) (after excluding adenoma >=1 cm) (P > 0.05). The overall accuracy of NBI
      was 81.0 %, compared with 81.4 % for FICE (P = 0.867). The overall sensitivity
      and specificity of NBI and FICE were 84.6 and 78.0 % (P = 0.054); 75.1 and 86.5 %
      (P = 0.009), respectively. For polyps measuring <=5 mm, the accuracy was 79.4 %
      for NBI and 80.1 % for FICE (P = 0.835; sensitivity 81.9 vs. 74.5 %, P = 0.064;
      specificity 75.7 vs. 88.4 %, P = 0.006). CONCLUSIONS: The overall accuracy of NBI
      and FICE was similar for differentiating small polyp histologies during screening
      colonoscopy. However, better results should be achieved before using NBI or FICE
      as real-time optical biopsy of colorectal polyps in screening colonoscopy.

PMID- 25868633
TI  - Raloxifene Ameliorates Liver Fibrosis of Nonalcoholic Steatohepatitis Induced by
      Choline-Deficient High-Fat Diet in Ovariectomized Mice.
AB  - BACKGROUND AND AIM: The prevalence of nonalcoholic fatty liver disease (NAFLD) is
      higher in men than in women, but according to some epidemiological studies, this
      gender difference disappears after menopause. Estrogen therapy protects against
      NAFLD and nonalcoholic steatohepatitis (NASH) after menopause. We investigated
      the therapeutic effect of raloxifene, a second-generation selective estrogen
      receptor modulator, on NASH induced by a choline-deficient high-fat (CDHF) diet
      in female ovariectomized (OVX) mice. METHODS: Seven-week-old female C57BL/6J mice
      were divided into three experimental groups as follows: (1) sham operation (SHAM
      group), (2) ovariectomy (OVX group), and (3) ovariectomy + raloxifene
      (intraperitoneal injection, 3 mg/kg body weight/day; OVX + RLX group). These
      three groups of mice were fed a CDHF diet for 8 weeks; choline-sufficient high
      fat (CSHF) diet was used as control diet. Serum biochemical indicators of hepatic
      function and liver histological changes were evaluated. RESULTS: Compared with
      CSHF diet, ovariectomy enhances liver injury and fibrosis in CDHF diet-fed mice.
      Serum alanine aminotransferase (ALT) levels were significantly lower in the OVX +
      RLX group than in the OVX group. The OVX group developed extensive steatosis with
      inflammation and fibrosis. Lobular inflammatory scores and fibrosis staging in
      the OVX + RLX group were significantly lower than in the OVX group. Furthermore,
      the OVX + RLX group exhibited significantly higher expression of hepatic estrogen
      receptor-alpha, which was significantly lower in the OVX group than in the SHAM
      group. CONCLUSIONS: Raloxifene may ameliorate progression of liver fibrosis of
      NASH induced by CDHF diet in ovariectomized female mice, and up-regulation of
      estrogen receptor-alpha may play an important role in the beneficial effects of
      raloxifene on NASH.

PMID- 25868635
TI  - Outcomes After Anterior Cruciate Ligament Reconstruction Using the Norwegian Knee
      Ligament Registry of 4691 Patients: How Does Meniscal Repair or Resection Affect
      Short-term Outcomes?
AB  - BACKGROUND: While the effects of concurrent meniscal resection and anterior
      cruciate ligament reconstruction (ACLR) are known to decrease patient outcomes
      and increase the rate of osteoarthritis over the long term, overall short-term
      patient functional outcomes in a large cohort of patients are not well known.
      PURPOSE/HYPOTHESIS: The purpose of this study was to compare the preoperative and
      2-year postoperative Knee Injury and Osteoarthritis Outcome Score (KOOS) subscale
      scores after ACLR with and without meniscal injury. The hypothesis was that, in
      comparison with an isolated ACLR, patients with a medial meniscal (MM) or lateral
      meniscal (LM) resection with an ACLR would have significantly decreased 2-year
      postoperative KOOS outcomes, while those with an ACLR with an MM or LM repair
      would be indistinguishable from isolated ACLR. STUDY DESIGN: Cohort study; Level
      of evidence, 2. METHODS: The Norwegian Knee Ligament Registry (NKLR) was used to
      evaluate outcomes for a total of 4691 patients with primary ACLR. The KOOS
      scoring system was used to evaluate patients on 5 subscales (Pain, Other
      Symptoms, Activities of Daily Life [ADL], Sport and Recreation Function, and
      Quality of Life [QoL]) at time of surgery and at 2-year postoperative follow-up.
      Patients with isolated ACLR and ACLR with LM repair, LM resection, MM repair, or
      MM resection were compared using multiple linear regression modeling. RESULTS:
      Preoperatively, in comparison with isolated ACLR, patients who had an ACLR with
      either an MM repair or MM resection had significantly lower scores for all KOOS
      subscores, and LM repair had significantly decreased scores on the Other
      Symptoms, Pain, and ADL subscales. Postoperatively, in comparison with isolated
      ACLR, 2-year KOOS outcomes were not significantly different between patients with
      ACLR and LM repair, MM resection, or LM resection; however, those with MM repair
      had significantly lower scores on the Other Symptoms and QoL subscales.
      CONCLUSION: Patients with ACLR with meniscal resections do not exhibit decreased
      clinical outcomes at 2 years postoperatively. It is recommended that clinicians
      follow patients with ACLR and concurrent meniscal treatment for longer than 2
      years postoperatively.

PMID- 25868636
TI  - Functional Testing Differences in Anterior Cruciate Ligament Reconstruction
      Patients Released Versus Not Released to Return to Sport.
AB  - BACKGROUND: No standardized return-to-activity or sport guidelines currently
      exist after anterior cruciate ligament (ACL) reconstruction. Isokinetic testing
      and unilateral hop testing, which have construct validity, are often used to make
      the determination of when a patient is ready to return to sport. Neither of these
      measures has been reported to be predictive of subsequent injuries. PURPOSE: To
      compare the performance on 2 functional tests of ACL reconstruction patients
      released to return to activity versus those who have not been released based on
      clinical impairment measures. STUDY DESIGN: Cohort study; Level of evidence, 3.
      METHODS: A total of 98 patients were examined by the treating orthopaedic surgeon
      6 months after ACL reconstruction for traditional impairment measures, including
      swelling, range of motion, strength, and graft stability. After this examination,
      all subjects completed the functional testing, consisting of the Functional
      Movement Screen (FMS) and the Lower Quarter Y Balance Test (YBT-LQ), by an
      experienced tester who was blinded to the results of the clinical examination. On
      the basis of the clinical examination, all patients were grouped as being ready
      to return to sport or not being ready. Performance on the functional tests, as
      measured by overall performance and side-to-side asymmetry, was compared between
      the 2 groups using independent-samples t tests (P < .05). RESULTS: No difference
      existed between the groups with regard to the descriptive characteristics, with
      the exception that the group not cleared was younger (21.0 +/- 7.4 years) than
      the group that was cleared (25.6 +/- 13.2 years). Performance on the YBT-LQ
      revealed that no differences existed between groups when examining reach symmetry
      for any of the reach directions. In addition, no differences were found between
      groups when looking at the average reach score normalized to limb length for
      either the surgical or nonsurgical leg. Patients in the cleared group exhibited a
      similar score on the FMS (12.7 +/- 2.9) compared with the noncleared group (12.8
      +/- 2.7). Similarly, no differences were observed for the number of asymmetries;
      however, both groups averaged 1 asymmetry during the testing. CONCLUSION:
      Clinical impairment measures do not appear to be related to measured functional
      ability. Performance on both functional tests, the FMS and YBT-LQ, at 6 months
      would suggest that the typical patient in both groups would be at a greater risk
      of lower extremity injury, based on currently published research.

PMID- 25868637
TI  - Low Serum Vitamin D Is Not Correlated With the Severity of a Rotator Cuff Tear or
      Retear After Arthroscopic Repair.
AB  - BACKGROUND: Despite the essential role of vitamin D in muscle function, the
      prevalence of vitamin D deficiency has been reported to be very high. Recently,
      low vitamin D level was found to correlate with fatty degeneration of the rotator
      cuff tendon in humans and to negatively affect early healing at the rotator cuff
      repair site in an animal study. However, the effects of vitamin D level on
      severity of rotator cuff tear and healing after surgical repair have not been
      documented. PURPOSE: To evaluate (1) the prevalence of vitamin D deficiency among
      patients who underwent arthroscopic repair for a full-thickness rotator cuff
      tear, (2) the relationship of vitamin D level with severity of the rotator cuff
      tear, and (3) surgical outcomes after repair. STUDY DESIGN: Cohort study; Level
      of evidence, 2. METHODS: A consecutive series of 91 patients (age, 50-65 years)
      who underwent arthroscopic rotator cuff repair for full-thickness, small-sized to
      massive tears were evaluated. Preoperative serum vitamin D levels (25
      hydroxyvitamin) were analyzed to detect correlations with the features of a
      preoperative rotator cuff tear as well as postoperative structural and functional
      outcomes. All patients were followed clinically for a minimum of 1 year. RESULTS:
      Preoperative vitamin D levels were deficient (<20 ng/mL) in 80 subjects (88%),
      insufficient (20-30 ng/mL) in 8 subjects (9%), and normal (>30 ng/mL) in 3
      subjects (3%). No correlation was found between preoperative tear size (P = .23),
      extent of retraction (P = .60), degree of fatty infiltration of each cuff muscle
      (P > .50 each), or the global fatty infiltration index (P = .32). Similarly, no
      correlations were detected between vitamin D level and postoperative Sugaya type
      (P = .66) or any of the functional outcome scores (P > .50 each). CONCLUSION: Low
      serum vitamin D level was not related to tear size, extent of retraction, or the
      degree of fatty infiltration in cuff muscles. It also had no significant
      relationships with postoperative structural integrity and functional outcomes
      after arthroscopic repair. The results suggest that low serum vitamin D level is
      not a significant risk factor for the severity of rotator cuff tear or poor
      healing after repair.

PMID- 25868638
TI  - Intestinal obstruction: predictor of poor prognosis in colorectal carcinoma?
AB  - OBJECTIVES: The goal of this study was to assess the relationship between
      intestinal obstruction and the prognosis of colorectal carcinoma. METHODS: Data
      pertaining to 4,501 colorectal carcinoma patients were extracted from the
      national colorectal registry and analysed. Survival analysis was performed using
      the Kaplan-Meier method. The log-rank test was used to compare the survival rate
      between patients with intestinal obstruction and those without intestinal
      obstruction. The p-values<0.05 were considered to indicate statistical
      significance. Simple Cox proportional hazards regression analysis was used to
      estimate the crude hazard ratio of mortality from colorectal cancer. RESULTS:
      Intestinal obstruction was reported in more than 13% of patients. The 3-year
      survival rate after treatment was 48.3% (95% confidence interval [CI], 43.9 to
      52.8) for patients with intestinal obstruction (n=593) and 54.9% (95% CI, 53.1 to
      56.6) for patients without intestinal obstruction (n=3,908). The 5-year survival
      rate for patients with intestinal obstruction was 37.3% (95% CI, 31.9 to 42.8),
      which was lower than that of patients without intestinal obstruction (45.6%; 95%
      CI, 43.5 to 47.7). After adjusting the hazard ratio for other prognostic
      variables, intestinal obstruction had a statistically significant negative
      correlation with the survival rate of colorectal cancer patients, with an
      adjusted hazard ratio of 1.22 (p=0.008). CONCLUSIONS: The presence of intestinal
      obstruction is associated with a lower survival rate among colorectal cancer
      patients.

PMID- 25868639
TI  - Development and application of patient decision aids.
AB  - With the current overdiagnosis of thyroid cancer resulting from routine screening
      in Korea, it is necessary to educate the public that not all cancers are
      malignant. The exposure to patient decision aids (PtDAs) compared to usual care
      reduced the number of people choosing to undergo prostate-specific antigen
      screening. This article introduces the definition, usefulness, and developmental
      processes of PtDAs and suggests the urgent need for a Korean PtDA related to
      thyroid cancer screening. 

PMID- 25868640
TI  - Macrocyclic amphiphiles.
AB  - In this critical review, we summarize recent results in the investigation of
      macrocyclic amphiphiles, amphiphiles based on macrocyclic frameworks. These
      interesting molecules have drawn a lot of attention over the past decades due to
      their unique superiority in self-assembly processes and other advantages.
      Compared with traditional linear amphiphiles, macrocyclic amphiphiles can be
      tailored to promote their self-assembly into various well-defined architectures
      by locating hydrophilic and hydrophobic chains on the respective sides. Since
      macrocyclic amphiphiles can be regarded as "surfactants" with host-guest
      recognition sites, they may be highly beneficial for applications where guest
      molecules must be stabilized, transported or protected in aqueous media.
      Considering the abundant research results on the host-guest chemistry of
      macrocycles, the use of macrocyclic amphiphiles in the fabrication of
      multidimensional and hierarchical self-assemblies may also provide interesting
      new topological structures. Moreover, the interactions of their self-assemblies
      can be mediated by molecular recognition, which may further our understanding of
      biological processes. 

PMID- 25868642
TI  - Oncogenic drivers and mitochondrial dependency.

PMID- 25868641
TI  - Paradigm Shifts in Atherosclerotic Renovascular Disease: Where Are We Now?
AB  - Results of recent clinical trials and experimental studies indicate that whereas
      atherosclerotic renovascular disease can accelerate both systemic hypertension
      and tissue injury in the poststenotic kidney, restoring vessel patency alone is
      insufficient to recover kidney function for most subjects. Kidney injury in
      atherosclerotic renovascular disease reflects complex interactions among vascular
      rarefication, oxidative stress injury, and recruitment of inflammatory cellular
      elements that ultimately produce fibrosis. Classic paradigms for simply restoring
      blood flow are shifting to implementation of therapy targeting mitochondria and
      cell-based functions to allow regeneration of vascular, glomerular, and tubular
      structures sufficient to recover, or at least stabilize, renal function. These
      developments offer exciting possibilities of repair and regeneration of kidney
      tissue that may limit progressive CKD in atherosclerotic renovascular disease and
      may apply to other conditions in which inflammatory injury is a major common
      pathway. 

PMID- 25868643
TI  - Marital status, labour force activity and mortality: a study in the USA and six
      European countries.
AB  - AIMS: Labour force activity and marriage share some pathways through which they
      potentially influence health. In this paper, we examine whether marriage and
      labour force participation interact in the way they influence mortality in the
      USA and six European countries. METHODS: We used data from the US National Health
      Interview Survey linked to the National Death Index, and national mortality
      registry data for Austria, England/Wales, Finland, Hungary, Norway and Spain
      (specifically, the Basque country) during 1999-2007, for men and women aged 30-59
      years at baseline. We used Poisson regression to estimate both the additive
      (relative excess risk due to interaction) and multiplicative interactions between
      marriage and labour force activity on mortality. RESULTS: Labour force inactivity
      was associated with higher mortality, but this association was stronger for
      unmarried, rather than married, individuals. Likewise, being unmarried was
      associated with higher mortality, but this association was stronger for inactive
      than for active individuals. To illustrate, among US women out of the labour
      force, being unmarried was associated with a 3.98 times (95%CI 3.28-4.82) higher
      risk of dying than being married; whereas the relative risk (RR) was 2.49 (95%CI
      2.10-2.94), for women who were active in the labour market. Although this
      interaction between marriage and labour force activity was only significant for
      women on a multiplicative scale, there was a significant additive interaction for
      both men and women. The pattern was similar across all countries. CONCLUSIONS:
      Marriage attenuated the increased mortality risk associated with labour force
      inactivity; while labour force activity attenuated the mortality risk associated
      with being unmarried. Our study emphasizes the importance of public health and
      social policies that improve the health and well-being of unmarried and inactive
      men and women.

PMID- 25868644
TI  - Eye Lens Opacities Among Physicians Occupationally Exposed to Ionizing Radiation.
AB  - We compared the frequency of lens opacities among physicians with and without
      occupational exposure to ionizing radiation, and estimated dose-response between
      cumulative dose and opacities. We conducted ophthalmologic examinations of 21
      physicians with occupational exposure to radiation and 16 unexposed physicians.
      Information on cumulative radiation doses (mean 111 mSv) was based on dosimeter
      readings recorded in a national database on occupational exposures. Lens changes
      were evaluated using the Lens Opacities Classification System II, with an
      emphasis on posterior subcapsular (PSC) and cortical changes. Among the exposed
      physicians, the prevalences of cortical and PSC changes were both 11% (3/21), and
      the corresponding frequencies in the unexposed group were 44% (n = 7) and 6% (n =
      1). For dose-response analysis, the data were pooled with 29 exposed physicians
      from our previous study. No association of either type of lens changes with
      cumulative recorded dose was observed. Our findings do not indicate an increased
      frequency of lens opacities in physicians with occupational exposure to ionizing
      radiation. However, the subjects in this study have received relatively low doses
      and therefore the results do not exclude small increases in lens opacities or
      contradict the studies reporting increases among interventional cardiologists
      with materially higher cumulative doses. 

PMID- 25868645
TI  - Involvement of the TetR-Type Regulator PaaR in the Regulation of Pristinamycin I
      Biosynthesis through an Effect on Precursor Supply in Streptomyces
      pristinaespiralis.
AB  - Pristinamycin I (PI), produced by Streptomyces pristinaespiralis, is a
      streptogramin type B antibiotic, which contains two proteinogenic and five
      aproteinogenic amino acid precursors. PI is coproduced with pristinamycin II
      (PII), a member of streptogramin type A antibiotics. The PI biosynthetic gene
      cluster has been cloned and characterized. However, thus far little is understood
      about the regulation of PI biosynthesis. In this study, a TetR family regulator
      (encoded by SSDG_03033) was identified as playing a positive role in PI
      biosynthesis. Its homologue, PaaR, from Corynebacterium glutamicum serves as a
      transcriptional repressor of the paa genes involved in phenylacetic acid (PAA)
      catabolism. Herein, we also designated the identified regulator as PaaR. Deletion
      of paaR led to an approximately 70% decrease in PI production but had little
      effect on PII biosynthesis. Identical to the function of its homologue from C.
      glutamicum, PaaR is also involved in the suppression of paa expression. Given
      that phenylacetyl coenzyme A (PA-CoA) is the common intermediate of the PAA
      catabolic pathway and the biosynthetic pathway of L-phenylglycine (L-Phg), the
      last amino acid precursor for PI biosynthesis, we proposed that derepression of
      the transcription of paa genes in a DeltapaaR mutant possibly diverts more PA-CoA
      to the PAA catabolic pathway, thereby with less PA-CoA metabolic flux toward L
      Phg formation, thus resulting in lower PI titers. This hypothesis was verified by
      the observations that PI production of a DeltapaaR mutant was restored by L-Phg
      supplementation as well as by deletion of the paaABCDE operon in the DeltapaaR
      mutant. Altogether, this study provides new insights into the regulation of PI
      biosynthesis by S. pristinaespiralis. IMPORTANCE: A better understanding of the
      regulation mechanisms for antibiotic biosynthesis will provide valuable clues for
      Streptomyces strain improvement. Herein, a TetR family regulator PaaR, which
      serves as the repressor of the transcription of paa genes involved in
      phenylacetic acid (PAA) catabolism, was identified as playing a positive role in
      the regulation of pristinamycin I (PI) by affecting the supply of one of seven
      amino acid precursors, L-phenylglycine, in Streptomyces pristinaespiralis. To our
      knowledge, this is the first report describing the interplay between PAA
      catabolism and antibiotic biosynthesis in Streptomyces strains. Considering that
      the PAA catabolic pathway and its regulation by PaaR are widespread in antibiotic
      producing actinomycetes, it could be suggested that PaaR-dependent regulation of
      antibiotic biosynthesis might commonly exist.

PMID- 25868648
TI  - Detection and termination of an extended low-frequency hospital outbreak of GIM-1
      producing Pseudomonas aeruginosa ST111 in Germany.
AB  - BACKGROUND: Metallo-beta-lactamase German imipenemase-1 (GIM-1)-mediated
      carbapenem resistance is emerging in Germany but has not spread beyond a very
      localized region. The aim of this study was to describe the first outbreak of an
      extensively drug-resistant GIM-1-carrying Pseudomonas aeruginosa strain affecting
      29 patients in a tertiary care hospital from 2002-2013. METHODS: The outbreak was
      studied retrospectively and prospectively by a combination of molecular methods
      (carbapenemase polymerase chain reaction [PCR]), genotyping (DiversiLab, pulsed
      field gel electrophoresis and multi-locus sequence typing, bioMerieux, Marcy
      l'Etoile, France), descriptive epidemiology, and extensive environmental
      investigations using swabs with liquid transport medium, blaGIM-1 PCR, directly
      from the medium and culture. RESULTS: Of the 29 affected patients, 24 had been
      admitted to a surgical intensive care unit at some point, where environmental
      sampling revealed a high burden of blaGIM-1 in the wastewater system. The
      outbreak strain was found in several sinks and on a reusable hair washbasin.
      Initially, general infection control measures were applied; thereafter, specific
      measures were implemented, including the restriction of washbasin use. Continued
      surveillance over a period of 2 years has revealed no further case of GIM-1
      carrying Pseudomonas aeruginosa. CONCLUSION: This long-term outbreak highlights
      the potential of molecular methods in surveillance for multidrug-resistant
      pathogens and in environmental sampling and the successful containment by
      application of specific control measures targeting biofilms within sink drains as
      potential environmental reservoirs for P aeruginosa.

PMID- 25868649
TI  - Pneumonia cases following an EF-5 tornado.
AB  - BACKGROUND: Infections following a natural disaster such as an EF-5 tornado can
      be atypical and difficult to treat. Studies have looked at illness following
      several natural disasters, but few have studied respiratory illness following a
      tornado. MATERIALS AND METHODS: A review of patients with pneumonia admitted
      during the period from May 22, 2009, through May 21, 2012, was completed. The
      Tornado Zone Group included adult patients who lived or worked in the tornado
      zone during the year following the tornado. Data were isolated by number of
      pneumonia cases within and outside the tornado zone per month per year. RESULTS:
      An analysis of variance comparing the number of pneumonia cases from the tornado
      zone per month per year was significant at F2,38 = 12.93 and P < .001, with
      increased cases in the Tornado Zone Group (P < .05). A t test comparing age of
      pneumonia patients found Tornado Zone patients to be younger than controls (t390
      = 5.14; P < .01). Microbes isolated from the Tornado Zone Group included uncommon
      pathogens not isolated during the 2 years prior. DISCUSSION: The number of
      pneumonia cases may increase following tornadoes. Although current guidelines
      recommend narrow-spectrum antibiotics for community-acquired pneumonia, results
      of this study suggest the possible need for broader antimicrobial coverage after
      tornadoes.

PMID- 25868646
TI  - Biochemical and Functional Characterization of the NurA-HerA Complex from
      Deinococcus radiodurans.
AB  - In archaea, the NurA nuclease and HerA ATPase/helicase, together with the Mre11
      Rad50 complex, function in 3' single-stranded DNA (ssDNA) end processing during
      homologous recombination (HR). However, bacterial homologs of NurA and HerA have
      not been characterized. From Deinococcus radiodurans, we identified the manganese
      dependent 5'-to-3' ssDNA/double-stranded DNA (dsDNA) exonuclease/endonuclease
      NurA (DrNurA) and the ATPase HerA (DrHerA). These two proteins stimulated each
      other's activity through direct protein-protein interactions. The N-terminal HAS
      domain of DrHerA was the key domain for this interaction. Several critical
      residues of DrNurA and DrHerA were verified by site-directed mutational analysis.
      Temperature-dependent activity assays confirmed that the two proteins had
      mesophilic features, with optimum activity temperatures 10  degrees C to 15 
      degrees C higher than their optimum growth temperatures. Knocking out either nurA
      or herA affected cell proliferation by shortening the growth phase, especially
      for growth at a high temperature (37  degrees C). In addition, both mutant
      strains displayed almost 10-fold-reduced intermolecular recombination efficiency,
      indicating that DrNurA and DrHerA might be involved in homologous recombination
      in vivo. However, single- and double-gene deletions did not show significantly
      decreased radioresistance. Our results confirmed that the biochemical activities
      of bacterial NurA and HerA proteins were conserved with archaea. Our phenotypical
      results suggested that these proteins might have different functions in bacteria.
      IMPORTANCE: Deinococcus radiodurans NurA (DrNurA) was identified as a manganese
      dependent 5'-to-3' ssDNA/dsDNA exonuclease/endonuclease, and Deinococcus
      radiodurans HerA (DrHerA) was identified as an ATPase. Physical interactions
      between DrNurA and DrHerA explained mutual stimulation of their activities. The N
      terminal HAS domain on DrHerA was identified as the interaction domain. Several
      essential functional sites on DrNurA and DrHerA were characterized. Both DrHerA
      and DrNurA showed mesophilic biochemical features, with their optimum activity
      temperatures 10  degrees C to 15  degrees C higher than their optimum growth
      temperatures in vitro. Knockout of nurA or herA led to abnormal cell
      proliferation and reduced intermolecular recombination efficiency but no obvious
      effect on radioresistence.

PMID- 25868647
TI  - Quorum Sensing Is Accompanied by Global Metabolic Changes in the Opportunistic
      Human Pathogen Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa uses N-acyl-homoserine lactone (AHL)-dependent quorum
      sensing (QS) systems to control the expression of secreted effectors. These
      effectors can be crucial to the ecological fitness of the bacterium, playing
      roles in nutrient acquisition, microbial competition, and virulence. In this
      study, we investigated the metabolic consequences of AHL-dependent QS by
      monitoring the metabolic profile(s) of a lasI rhlI double mutant (unable to make
      QS signaling molecules) and its wild-type progenitor as they progressed through
      the growth curve. Analysis of culture supernatants by (1)H-nuclear magnetic
      resonance ((1)H-NMR) spectroscopy revealed that at the point where AHL
      concentrations peaked in the wild type, the metabolic footprints (i.e.,
      extracellular metabolites) of the wild-type and lasI rhlI mutant diverged.
      Subsequent gas chromatography-mass spectrometry (GC-MS)-based analysis of the
      intracellular metabolome revealed QS-dependent perturbations in around one-third
      of all identified metabolites, including altered concentrations of tricarboxylic
      acid (TCA) cycle intermediates, amino acids, and fatty acids. Further targeted
      fatty acid methyl ester (FAME) GC-MS-based profiling of the cellular total fatty
      acid pools revealed that QS leads to changes associated with decreased membrane
      fluidity and higher chemical stability. However, not all of the changes we
      observed were necessarily a direct consequence of QS; liquid chromatography (LC)
      MS analyses revealed that polyamine levels were elevated in the lasI rhlI mutant,
      perhaps a response to the absence of QS-dependent adaptations. Our data suggest
      that QS leads to a global readjustment in central metabolism and provide new
      insight into the metabolic changes associated with QS during stationary-phase
      adaptation. IMPORTANCE: Quorum sensing (QS) is a transcriptional regulatory
      mechanism that allows bacteria to coordinate their gene expression profile with
      the population cell density. The opportunistic human pathogen Pseudomonas
      aeruginosa uses QS to control the production of secreted virulence factors. In
      this study, we show that QS elicits a global "metabolic rewiring" in P.
      aeruginosa. This metabolic rerouting of fluxes is consistent with a variety of
      drivers, ranging from altered QS-dependent transcription of "metabolic genes"
      through to the effect(s) of global "metabolic readjustment" as a consequence of
      QS-dependent exoproduct synthesis, as well as a general stress response, among
      others. To our knowledge, this is the first study of its kind to assess the
      global impact of QS on the metabolome.

PMID- 25868650
TI  - Predictors for compliance of standard precautions among nursing students.
AB  - BACKGROUND: We aimed to investigate the frequency of standard precautions (SPs)
      compliance and the factors affecting the compliance among nursing students (NSs).
      METHODS: A cross-sectional survey study guided by the health belief model was
      conducted in 2009. The study questionnaire is valid (content validity index,
      0.81) and reliable (Cronbach alpha range, 0.65-0.94). RESULTS: There were 678
      questionnaires analyzed, with a response rate of 68.9%. The mean frequency score
      of SPs compliance was 4.38 +/- 0.40 out of 5. Tukey honest significant difference
      post hoc test indicated that year 2 and year 4 students had better SPs compliance
      than year 3 students. Further analysis using a univariate general linear model
      identified an interaction effect of perceived influence of nursing staff and year
      of study (F1,593 = 3.72; P < .05). The 5 following predictors for SPs compliance
      were identified: knowledge of SPs, perceived barriers, adequacy of training,
      management support, and influence of nursing staff. CONCLUSION: Although the SPs
      compliance among NSs was high, the compliance varied by year of study and was
      affected by the nursing staff. Furthermore, SPs compliance among NSs can be
      enhanced by increasing SPs knowledge, providing more SPs training, promoting
      management support, reducing identified SPs barriers, and improving nursing staff
      compliance to SPs.

PMID- 25868651
TI  - Individual versus pooled multiple-lumen blood cultures for the diagnosis of
      intravascular catheter-related infections.
AB  - BACKGROUND: The current gold standard method for diagnosis of central-line
      associated bloodstream infections (CLABSIs) requires central venous catheter
      removal and a positive culture of the CVC tip with a positive peripheral blood
      culture. STUDY DESIGN: Comparative study. METHODS: We compared individual blood
      cultures from each catheter lumen versus a pooled-blood culture bottle containing
      blood samples from every catheter lumen for the diagnosis of CLABSI. RESULTS: The
      pooled blood culture had the same sensitivity as the individually cultured
      central venous catheter lumens (85%) to detect CLABSI. A high correlation was
      found when we compared the pooled culture with any positive lumen result (kappa =
      0.98) but not when compared with any single lumen. CONCLUSIONS: Sampling multiple
      lumens from a central line and incubating them in the same blood culture bottle
      is as effective as individual blood cultures for the diagnosis of colonization or
      CLABSI and is a better choice than sampling only 1 lumen when sending 3 different
      blood culture bottles is not possible.

PMID- 25868652
TI  - Fatal attraction: the intuitive appeal of GMO opposition.
AB  - Public opposition to genetically modified organisms (GMOs) remains strong. By
      contrast, studies demonstrate again and again that GM crops make a valuable
      contribution to the development of a sustainable type of agriculture. The
      discrepancy between public opinion and the scientific evidence requires an
      explanation. We argue that intuitive expectations about the world render the
      human mind vulnerable to particular misrepresentations of GMOs. We explain how
      the involvement of particular intuitions accounts for the popularity,
      persistence, and typical features of GM opposition and tackle possible objections
      to our approach. To conclude, we discuss the implications for science education,
      science communication, and the environmental movement.

PMID- 25868653
TI  - Flowers and mycorrhizal roots--closer than we think?
AB  - Roots and flowers are formed at the extreme ends of plants and they differ in
      almost every aspect of their development and function; even so, they exhibit
      surprising molecular commonalities. For example, the calcium and calmodulin
      dependent protein kinase (CCaMK) plays a central role in root symbioses with
      fungi and bacteria, but is also highly expressed in developing anthers. Moreover,
      independent evidence from transcriptomics, phylogenomics, and genetics reveals
      common developmental elements in root symbioses and reproductive development. We
      discuss the significance of these overlaps, and we argue that an integrated
      comparative view of the two phenomena will stimulate research and provide new
      insight, not only into shared components, but also into the specific aspects of
      anther development and root symbioses. 

PMID- 25868654
TI  - State-to-state vacuum ultraviolet photodissociation study of CO2 on the formation
      of state-correlated CO(X(1)Sigma(+); v) with O((1)D) and O((1)S) photoproducts at
      11.95-12.22 eV.
AB  - The state-to-state photodissociation of CO2 is investigated in the VUV range of
      11.94-12.20 eV by using two independently tunable vacuum ultraviolet (VUV) lasers
      and the time-sliced velocity-map-imaging-photoion (VMI-PI) method. The spin
      allowed CO(X(1)Sigma(+); v = 0-18) + O((1)D) and CO(X(1)Sigma(+); v = 0-9) +
      O((1)S) photoproduct channels are directly observed from the measurement of time
      sliced VMI-PI images of O((1)D) and O((1)S). The total kinetic energy release
      (TKER) spectra obtained based on these VMI-PI images shows that the observed
      energetic thresholds for both the O((1)D) and O((1)S) channels are consistent
      with the thermochemical thresholds. Furthermore, the nascent vibrational
      distributions of CO(X(1)Sigma(+); v) photoproducts formed in correlation with
      O((1)D) differ significantly from that produced in correlation with O((1)S),
      indicating that the dissociation pathways for the O((1)D) and O((1)S) channels
      are distinctly different. For the O((1)S) channel, CO(X(1)Sigma(+); v)
      photoproducts are formed mostly in low vibrational states (v = 0-2), whereas for
      the O((1)D) channel, CO(X(1)Sigma(+); v) photoproducts are found to have
      significant populations in high vibrationally excited states (v = 10-16). The
      anisotropy beta parameters for the O((1)D) + CO(X(1)Sigma(+); v = 0-18) and
      O((1)S) + CO(X(1)Sigma(+); v = 0-9) channels have also been determined from the
      VMI-PI measurements, indicating that CO2 dissociation to form the O((1)D) and
      O((1)S) channels is faster than the rotational periods of the VUV excited CO2
      molecules. We have also calculated the excited singlet potential energy surfaces
      (PESs) of CO2, which are directly accessible by VUV excitation, at the ab initio
      quantum multi-reference configuration interaction level of theory. These
      calculated PESs suggest that the formation of CO(X(1)Sigma(+)) + O((1)S)
      photoproducts occurs nearly exclusively on the 4(1)A' PES, which is generally
      repulsive with minor potential energy ripples along the OC-O stretching
      coordinate. The formation of CO(X(1)Sigma(+)) + O((1)D) photofragments can
      proceed by non-adiabatic transitions from the 4(1)A' PES to the lower 3(1)A' PES
      of CO2via the seam of conical intersections at a near linear OCO configuration,
      followed by the direct dissociation on the 3(1)A' PES. The theoretical PES
      calculations are consistent with the experimental observation of prompt CO2
      dissociation and high rotational and vibrational excitations for CO(X(1)Sigma(+))
      photoproducts. 

PMID- 25868655
TI  - Knockdown of a putative alanine aminotransferase gene affects amino acid content
      and flight capacity in the Colorado potato beetle Leptinotarsa decemlineata.
AB  - Alanine aminotransferase (ALT) plays important physiological and biochemical
      roles in insect. In this study, a full-length Ldalt cDNA was cloned from
      Leptinotarsa decemlineata. It was ubiquitously expressed in the eggs, larvae,
      pupae and adults. In the adults, Ldalt mRNA was widely distributed in thorax
      muscles, fat body, midgut, foregut, hindgut, Malpighian tubules, ventral ganglion
      and epidermis, with the expression levels from the highest to the lowest. Two
      double-stranded RNAs (dsRNAs) (dsLdalt1 and dsLdalt2) targeting Ldalt were
      constructed and bacterially expressed. After adults fed on dsLdalt1- and dsLdalt2
      immersed foliage for 3 day, Ldalt mRNA abundance was significantly decreased by
      79.5 and 71.1 %, and ALT activities were significantly reduced by 64.5 and 67.6
      %, respectively. Moreover, silencing Ldalt affected free amino acid contents.
      Lysine was decreased by 100.0 and 100.0 %, and arginine was reduced by 87.5 and
      89.4 %, respectively, in the hemolymph from dsLdalt1- and dsLdalt2-ingested
      beetles, compared with control ones. In contrast, proline was increased by 88.7
      and 96.4 %. Furthermore, ingestion of dsLdalt1 and dsLdalt2 significantly
      decreased flight speed, shortened flight duration time and flight distance. In
      addition, knocking down Ldalt significantly increased adult mortality. These data
      imply that LdALT plays important roles in amino acid metabolism and in flight in
      L. decemlineata. 

PMID- 25868656
TI  - A conjugate of the lytic peptide Hecate and gallic acid: structure, activity
      against cervical cancer, and toxicity.
AB  - Conjugate compounds constitute a new class of molecules of important biological
      interest mainly for the treatment of diseases such as cancer. The N-terminus
      region of cationic peptides has been described as important for their biological
      activity. The aim of this study was to evaluate the lytic peptide Hecate
      (FALALKALKKALKKLKKALKKAL) and the effect of conjugating this macromolecule with
      gallic acid (C7H6O5) in terms of structure, anti-cancer activity, and toxicity.
      An N-terminus GA-Hecate peptide conjugate was synthesized to provide information
      regarding the relationship between the amino-terminal region and its charge and
      the secondary structure and biological activity of the peptide; and the effects
      of gallic acid on these parameters. Peptide secondary structure was confirmed
      using circular dichroism (CD). The CD measurements showed that the peptide has a
      high incidence of alpha-helical structures in the presence of SDS and LPC, while
      GA-Hecate presented lower incidence of alpha-helical structures in the same
      chemical environment. An evaluation of the anti-cancer activity in HeLa cancer
      cells indicated that both peptides are active, but that coupling gallic acid at
      the N-terminus decreased the activity of the free peptide. GA-Hecate showed lower
      activity in non-tumor keratinocyte cells but higher hemolytic activity. Our
      findings suggest that the N-terminus of Hecate plays an important role in its
      activity against cervical cancer by affecting it secondary structure, toxicity,
      and hemolytic activity. This study highlights the importance of the N-terminus in
      antitumor activity and could provide an important tool for developing new anti
      cancer drugs. 

PMID- 25868657
TI  - Obstetric and neonatal outcome of pregnancies fathered by males on
      immunosuppression after solid organ transplantation.
AB  - Immunosuppressive drugs may influence spermatogenesis, but little is known about
      outcome of pregnancies fathered by transplanted males. We estimated risk of
      adverse outcomes in pregnancies (with data after the first trimester) fathered by
      males that had undergone organ transplantation and were treated with
      immunosuppression. A population-based study, linking data from the Norwegian
      transplant registry and the Medical Birth Registry of Norway during 1967-2009 was
      designed. All Norwegian men undergoing solid organ transplantation were included.
      Odds ratios for major malformations, preeclampsia, preterm delivery (<37 weeks)
      and small-for-gestational-age were obtained using logistic regression. A total of
      2463 transplanted males, fathering babies of 4614 deliveries before and 474
      deliveries after transplantation were identified. The risk of preeclampsia was
      increased (AOR: 7.4, 95% CI: 1.1-51.4,) after transplantation compared to prior
      to transplantation. No increased risk was found for congenital malformations or
      other outcomes when compared with pregnancies before transplantation or with the
      general population (2 511 506 births). Our results indicate an increased risk of
      preeclampsia mediated through the transplanted and immunosuppressed father.
      Importantly, no increased risk was found for other adverse obstetric outcomes or
      malformations, which may reassure male transplant recipients planning to father
      children. 

PMID- 25868658
TI  - The AMPK Agonist PT1 and mTOR Inhibitor 3HOI-BA-01 Protect Cardiomyocytes After
      Ischemia Through Induction of Autophagy.
AB  - Myocardial ischemia has become one of the main causes of sudden cardiac death
      worldwide. Autophagy has been demonstrated to protect cardiomyocytes from
      ischemia/reperfusion (I/R)-induced damage. A novel small molecule compound 2
      Chloro-5-[[5-[[5-(4,5-Dimethyl-2-nitrophenyl)-2-furanyl]methylene]-4,5-dihydro-4
      oxo-2-thiazolyl]amino]benzoic acid (PT1) has been previously shown to
      specifically activate 5'-adenosine monophosphate-activated protein kinase (AMPK).
      Because AMPK activation effectively induces autophagy, we tested the protective
      efficacy of PT1 on cardiomyocytes after oxygen glucose deprivation/reoxygenation
      (OGD/R) in vitro. Mouse neonatal cardiomyocytes were treated with PT1 after
      OGD/R. 3-[4-(1,3-benzodioxol-5-yl)-2-oxo-3-buten-1-yl]-3-hydroxy-1,3-dihydro-2H
      indol-2-one (3HOI-BA-01), a novel small compound showing potent inhibitory effect
      on mammalian target of rapamycin (mTOR) activation, was also tested for its
      cardioprotective effect, based on the established relationship between mTOR
      signaling and autophagy. Cell survival and autophagy-related signal pathways were
      examined after treatment with these agents. Our data indicate that both PT1 and
      3HOI-BA-01 enhance cell survival after OGD/R. As expected, both PT1 and 3HOI-BA
      01 induced autophagy in cardiomyocytes through activating AMPK pathway and
      inhibiting mTOR signaling, respectively. Induction of autophagy by PT1 and 3HOI
      BA-01 was responsible for their cardioprotective effect, since inhibition of
      autophagy abolished the protective efficacy. Furthermore, simultaneous
      administration of PT1 and 3HOI-BA-01 profoundly upregulated autophagy after OGD/R
      and significantly promoted survival of cardiomyocytes. In vivo administration of
      PT1 and 3HOI-BA-01 in a murine myocardial (I/R injury model remarkably reduced
      infarct size and induced autophagy. Taken together, our research suggests that
      PT1 and 3HOI-BA-01 could be promising therapeutic agents for myocardial ischemia.

PMID- 25868659
TI  - Influence of Different beta-Blockers on Platelet Aggregation in Patients With
      Coronary Artery Disease on Dual Antiplatelet Therapy.
AB  - INTRODUCTION: The use of beta-blockers in the treatment of patients with coronary
      heart disease is associated with a decrease in the frequency of angina pectoris
      and mortality of patients. Due to the severity of the disease and previous
      cardiovascular interventions, many patients with coronary artery disease (CAD)
      use dual antiplatelet therapy to achieve greater inhibition of platelet
      aggregation. The influence of beta-blockers on platelet aggregation in patients
      using antiplatelet therapy is not well understood. OBJECTIVE: To examine the
      effect of different beta-blockers on platelet aggregation in patients on dual
      antiplatelet therapy. METHODOLOGY: The study included 331 patients who were
      treated at the Department of Cardiology, Clinical Center Kragujevac during 2011.
      Patients were divided into 4 groups depending on the type of beta-blockers that
      were used (bisoprolol, nebivolol, metoprolol, and carvedilol). Platelet
      aggregation was measured using the multiplate analyzer and expressed through the
      value of adenosine diphosphate (ADP) test (to assess the effect of clopidogrel),
      ASPI test (to assess the effect of acetyl salicylic acid), TRAP test (to assess
      baseline platelet aggregation), and the ratio of ADP/TRAP and ASPI/TRAP ASPI/TRAP
      (ASPI - aranchidonic acid induced aggregation, TRAP - thrombin receptor
      activating peptide) representing the degree of inhibition of platelet aggregation
      compared to the basal value. In consideration were taken the representation of
      demographic, clinical characteristics, laboratory parameters, and cardiovascular
      medications between the groups. RESULTS: Patients who used nebivolol had a
      significantly lower value of the ratio of ADP/TRAP (0.39 +/- 0.30) compared to
      patients who used bisoprolol (0.48 +/- 0.26; P = .038), and trend toward the
      lower values of ADP test (328.0 +/- 197.3 vs 403.7 +/- 213.2; P = .059), while
      there was no statistically significant difference in values of other laboratory
      parameters of platelet function between other groups. CONCLUSION: Patients with
      CAD on dual antiplatelet therapy who used nebivolol had significantly lower
      levels of residual ADP-induced platelet aggregation compared to baseline than
      patients who used bisoprolol.

PMID- 25868661
TI  - The role of host abundance in regulating populations of freshwater mussels with
      parasitic larvae.
AB  - Host-parasite theory makes predictions about the influence of host abundance,
      competition for hosts, and parasite transmission on parasite population size, but
      many of these predictions are not well tested empirically. We experimentally
      examined these factors in ponds using two species of freshwater mussels with
      parasitic larvae that infect host fishes via different infection strategies. For
      both species, recruitment and larval survival were positively related to host
      abundance, but there was no apparent minimum host threshold and positive
      population growth occurred when an average of one fish per mussel was present.
      Recruitment increased rapidly with an initial increase in host abundance but
      appeared to approach an asymptote at moderate host abundance. Recruitment and
      larval survival did not differ according to whether mussel species occurred alone
      or in combination, providing no evidence for competition for hosts via acquired
      immunity. However, larval survival of the species that attracts hosts with a lure
      was higher than the species that infects hosts passively, but lower survival of
      the latter strategy was offset by higher fecundity, which resulted in comparable
      recruitment between the two species. The lack of evidence for competition for
      hosts or host saturation suggests that mussel recruitment is limited primarily by
      fecundity and larval transmission efficiency. Despite the lack of a minimum host
      abundance threshold, high variation in recruitment in all treatments suggests
      that population growth at low host abundance is limited by stochasticity. These
      results show that host-parasite interactions in natural situations may differ
      substantially from predictions based on models or laboratory findings.

PMID- 25868660
TI  - The impact of obstetric mode of delivery on childhood behavior.
AB  - PURPOSE: We investigated the hypothesis that mode of delivery affects childhood
      behavior and motor development and examined whether there are sex-specific
      associations, i.e., whether males and females have different risk estimates.
      METHODS: Families with infants born between December 2007 and May 2008 (N =
      11,134) were randomly selected and recruited to the Growing Up in Ireland study.
      Mode of delivery was classified into spontaneous vaginal delivery; instrumental
      vaginal delivery; emergency Cesarean section (CS); and elective CS. The 'Ages and
      Stages Questionnaire' was completed at age 9-months and the 'Strengths and
      Difficulties Questionnaire' at 3 years. Data were weighted to represent the
      national sample (N = 73,662) and multivariate logistic regression was used for
      the statistical analyses. RESULTS: At age 9 months, elective CS was associated
      with a delay in personal social skills [adjusted odds ratio, aOR 1.24; (95%
      confidence interval, CI 1.04, 1.48)] and gross motor function [aOR 1.62, (95% CI
      1.34, 1.96)], whereas emergency CS was associated with delayed gross motor
      function [aOR 1.30, (95% CI 1.06, 1.59)]. At age 3 years there was no
      significantly increased risk of an abnormal total SDQ score across all modes of
      delivery. CONCLUSIONS: Children born by elective CS may face a delay in cognitive
      and motor development at age 9 months. No increase in total SDQ score was found
      across all modes of delivery. Further investigation is needed to replicate these
      findings in other populations and explore the potential biological mechanisms.

PMID- 25868662
TI  - Differences in the resting platelet proteome and platelet releasate between
      healthy children and adults.
AB  - Major age-related diseases such as cardiovascular disease and cancer are the
      primary causes of morbidity and mortality in Australia and worldwide. In our
      recent study characterising differences in the plasma proteome between healthy
      children and adults, a large number of proteins differentially expressed with age
      were found to be of platelet origin. This study aimed to characterise differences
      in the resting platelet proteome and the platelet releasate of healthy children
      compared to healthy adults. This study represents the setup of a procedure for
      the proteomic analysis of platelets from children. Differentially expressed
      platelet proteins were identified using Two-dimensional Differential In-Gel
      Electrophoresis and mass spectrometry. Significant differences in the expression
      of nine proteins (1.1%) in the resting platelet proteome were observed in
      children compared to adults. Serotransferrin, fibrinogen alpha chain,
      glyceraldehyde-3 phosphate dehydrogenase, serum albumin, transgelin-2, calponin
      2/LIM and SH3 domain protein 1 and human chorionic gonadotropin 2039797 were up
      regulated, whereas thrombospondin-1 was down-regulated in children. Eleven
      proteins (1.5%) were differentially expressed in the platelet releasate of
      children compared to adults, where transferrin was also upregulated and TSP-1 was
      down regulated. Identified proteins are involved in processes including tissue
      and organ development, cell proliferation regulation and angiogenesis. Our
      results provide novel insights into platelet physiology as well as growth,
      development and ageing in healthy individuals. BIOLOGICAL SIGNIFICANCE: The
      incidence of major diseases such as cardiovascular disease (CVD) and cancer
      increase with increasing age and are the major causes of morbidity and mortality
      both in Australia and worldwide. As the aged population continues to increase
      dramatically, so too will the financial strains associated with the long term
      care of the elderly population. Compared to adults, children have a significantly
      lower incidence of major diseases such as thromboembolic disease. This suggests
      that children have a protective mechanism against the development of disease.
      Therefore, studies focussing on the molecular changes of proteins, the machinery
      of the cell, between children and adults are the key to determining the
      underlying mechanisms responsible for the onset of major diseases. A well-defined
      example of how protein expression can change with age is that of the plasma
      proteome. Significant differences in the expression of numerous plasma proteins
      between healthy children and adults have been recently demonstrated.
      Interestingly, a large number of differentially expressed proteins were found to
      be of platelet origin. This finding forms the basis for the current study,
      presenting as strong evidence for the age-specific differences of the platelet
      proteome.

PMID- 25868663
TI  - Proteomics research in India: an update.
AB  - After a successful completion of the Human Genome Project, deciphering the
      mystery surrounding the human proteome posed a major challenge. Despite not being
      largely involved in the Human Genome Project, the Indian scientific community
      contributed towards proteomic research along with the global community.
      Currently, more than 76 research/academic institutes and nearly 145 research labs
      are involved in core proteomic research across India. The Indian researchers have
      been major contributors in drafting the "human proteome map" along with
      international efforts. In addition to this, virtual proteomics labs, proteomics
      courses and remote triggered proteomics labs have helped to overcome the
      limitations of proteomics education posed due to expensive lab infrastructure.
      The establishment of Proteomics Society, India (PSI) has created a platform for
      the Indian proteomic researchers to share ideas, research collaborations and
      conduct annual conferences and workshops. Indian proteomic research is really
      moving forward with the global proteomics community in a quest to solve the
      mysteries of proteomics. A draft map of the human proteome enhances the
      enthusiasm among intellectuals to promote proteomic research in India to the
      world.This article is part of a Special Issue entitled: Proteomics in India.

PMID- 25868664
TI  - Clinical, morphological, biochemical, imaging and outcome parameters in 21
      individuals with mitochondrial maintenance defect related to FBXL4 mutations.
AB  - FBXL4 deficiency is a recently described disorder of mitochondrial maintenance
      associated with a loss of mitochondrial DNA in cells. To date, the genetic
      diagnosis of FBXL4 deficiency has been established in 28 individuals. This paper
      retrospectively reviews proxy-reported clinical and biochemical findings and
      evaluates brain imaging, morphological and genetic data in 21 of those patients.
      Neonatal/early-onset severe lactic acidosis, muscular hypotonia, feeding problems
      and failure to thrive is the characteristic pattern at first presentation. Facial
      dysmorphic features are present in 67% of cases. Seven children died (mean age 37
      months); 11 children were alive (mean age at follow-up 46 months), three children
      were lost to follow-up. All survivors developed severe psychomotor retardation.
      Brain imaging was non-specific in neonates but a later-onset, rapidly progressive
      brain atrophy was noted. Elevated blood lactate and metabolic acidosis were
      observed in all individuals; creatine kinase was elevated in 45% of measurements.
      Diagnostic workup in patient tissues and cells revealed a severe combined
      respiratory chain defect with a general decrease of enzymes associated with
      mitochondrial energy metabolism and a relative depletion of mitochondrial DNA
      content. Mutations were detected throughout the FBXL4 gene albeit with no clear
      delineation of a genotype-phenotype correlation. Treatment with "mitochondrial
      medications" did not prove effective. In conclusion, a clinical pattern of early
      onset encephalopathy, persistent lactic acidosis, profound muscular hypotonia and
      typical facial dysmorphism should prompt initiation of molecular genetic analysis
      of FBXL4. Establishment of the diagnosis permits genetic counselling, prevents
      patients undergoing unhelpful diagnostic procedures and allows for accurate
      prognosis.

PMID- 25868665
TI  - Vascular endothelial growth factors: multitasking functionality in metabolism,
      health and disease.
AB  - Vascular endothelial growth factors (VEGFs) bind to VEGF receptor tyrosine
      kinases (VEGFRs). The VEGF and VEGFR gene products regulate diverse regulatory
      pathways in mammalian development, health and disease. The interaction between a
      particular VEGF and its cognate VEGFR activates multiple signal transduction
      pathways which regulate different cellular responses including metabolism, gene
      expression, proliferation, migration, and survival. The family of VEGF isoforms
      regulate vascular physiology and promote tissue homeostasis. VEGF dysfunction is
      implicated in major chronic disease states including atherosclerosis, diabetes,
      and cancer. More recent studies implicate a strong link between response to VEGF
      and regulation of vascular metabolism. Understanding how this family of
      multitasking cytokines regulates cell and animal function has implications for
      treating many different diseases. 

PMID- 25868666
TI  - Amyloidosis in alkaptonuria.
AB  - Alkaptonuria (AKU) is an ultra-rare inborn error of metabolism developed from the
      lack of homogentisic acid oxidase activity, causing homogentisic acid (HGA)
      accumulation that produces an HGA-melanin ochronotic pigment, of hitherto unknown
      composition. Besides the accumulation of HGA, the potential role and presence of
      unidentified proteins has been hypothesized as additional causal factors involved
      in ochronotic pigment deposition. Evidence has been provided on the presence of
      serum amyloid A (SAA) in several AKU tissues, which allowed classifying AKU as a
      novel secondary amyloidosis. In this paper, we will briefly review all direct and
      indirect lines of evidence related to the presence of amyloidosis in AKU. We also
      report the first data on abnormal SAA serum levels in a cohort of AKU patients. 

PMID- 25833480
TI  - Population-based survey on disease insight, quality of life, and health-seeking
      behavior associated with female urinary incontinence.
AB  - PURPOSE: To evaluate disease insight, personal distress, and healthcare-seeking
      behavior of women with urinary incontinence (UI) to improve women's health in
      Korea. METHODS: In October 2012, 500 Korean women residing around Seoul, Incheon,
      and Gyeonggi-do were selected by random sampling for a population-based cross
      sectional survey conducted by computer-aided telephone interview. Sixteen
      questions, which included information on demographic characteristics, information
      sources, disease insights, and general health-seeking behavior, were used for
      data collection. RESULTS: Among the responders, 23.8% experienced UI, the
      prevalence of which increased with increasing age; 83.3% knew about UI through
      the mass media out of 98.2% apprehended people. Regarding general awareness of
      UI, 77.2% understood that UI is caused by aging. A total of 48.7% of subjects
      experienced societal restrictions because of UI. Most women in their 30s (25.6%)
      acquired UI information from the Internet, while those in their 50s and 60s (50
      59 years, 51.1%; 60-64 years, 42.4%) learned about UI through friends. Among
      subjects who did not have UI, 89.37% intended to see a doctor or consult a
      professional if they developed UI (83.2%). Among those with UI, however, only
      59.0% had talked about UI; 79.7% had talked with friends or associates, whereas
      only 23.2% had consulted a professional. CONCLUSIONS: Most respondents tended to
      obtain information on UI through the mass media. Subjects who did not have UI
      expressed their intention to consult a professional if they developed UI, while
      the percentage of subjects with UI who had consulted a professional was very low.
      Many women are ashamed of UI in Korea, which may be changed by providing
      efficient advertising with the right information and establishing a new
      perception of UI.

PMID- 25868668
TI  - A rationally designed peptidomimetic biosensor for sialic acid on cell surfaces.
AB  - We have developed peptidomimetic sialic acid (Sia) biosensors using boronic acid
      and arginine groups on the peptide backbone. The designed peptides were
      conjugated to fluorescent streptavidin via biotin enabling the optical labeling
      of cells. This approach provides unique opportunities to detect Sia composition
      on the cell surfaces and filopodia. 

PMID- 25868669
TI  - (3E,7E)-3,7-Bis(2-oxoindolin-3-ylidene)-5,7-dihydropyrrolo[2,3-f]indole
      2,6(1H,3H)-dione based polymers for ambipolar organic thin film transistors.
AB  - A novel acceptor, (3E,7E)-3,7-bis(2-oxoindolin-3-ylidene)-5,7-dihydropyrrolo[2,3
      f]indole-2,6(1H,3H)-dione, was reported. Donor-acceptor (D-A) polymer
      semiconductors using this new building block showed high ambipolar charge
      transport performance with hole and electron mobilities up to 0.19 and 0.09 cm(2)
      V(-1) s(-1), respectively, in thin film transistors. 

PMID- 25868670
TI  - Reducing Unnecessary Portable Pelvic Radiographs in Trauma Patients: A Resident
      Driven Quality Improvement Initiative.
AB  - Quality improvement is increasingly important in the changing health care
      climate. We aim to establish a methodology and identify critical factors leading
      to successful implementation of a resident-led radiology quality improvement
      intervention at the institutional level. Under guidance of faculty mentors, the
      first-year radiology residents developed a quality improvement initiative to
      decrease unnecessary STAT pelvic radiographs (PXRs) in hemodynamically stable
      trauma patients who would additionally receive STAT pelvic CT scans. Development
      and implementation of this initiative required multiple steps, including:
      establishing resident and faculty leadership, gathering evidence from published
      literature, cultivating multidisciplinary support, and developing and
      implementing an institution-wide ordering algorithm. A visual aid and brief
      questionnaire were distributed to clinicians for use during treatment of trauma
      cases to ensure sustainability of the initiative. At multiple time points, pre-
      and post-intervention, residents performed a retrospective chart review to
      evaluate changes in imaging-ordering trends for trauma patients. Chart review
      showed a decline in the number of PXRs for hemodynamically stable trauma
      patients, as recommended in the ordering algorithm: 78% of trauma patients
      received both a PXR and a pelvic CT scan in the first 24 hours of the initiative,
      compared with 26% at 1 month; 24% at 6 months; and 18% at 10 to 12 months
      postintervention. The resident-led radiology quality improvement initiative
      created a shift in ordering culture at an institutional level. Development and
      implementation of this algorithm exemplified the impact of a multidisciplinary
      collaborative effort involving multiple departments and multiple levels of the
      medical hierarchy. 

PMID- 25868671
TI  - Survey-Based Assessment of Patients' Understanding of Their Own Imaging
      Examinations.
AB  - PURPOSE: To perform a survey-based assessment of patients' knowledge of
      radiologic imaging examinations, including patients' perspectives regarding
      communication of such information. METHODS: Adult patients were given a voluntary
      survey before undergoing an outpatient imaging examination at our institution.
      Survey questions addressed knowledge of various aspects of the examination, as
      well as experiences, satisfaction, and preferences regarding communication of
      such knowledge. RESULTS: A total of 176 surveys were completed by patients
      awaiting CT (n = 45), MRI (n = 41), ultrasound (n = 46), and nuclear medicine (n
      = 44) examinations. A total of 97.1% and 97.8% of patients correctly identified
      the examination modality and the body part being imaged, respectively. A total of
      45.8% correctly identified whether the examination entailed radiation; 51.1% and
      71.4% of patients receiving intravenous or oral contrast, respectively, correctly
      indicated its administration. A total of 78.6% indicated that the ordering
      physician explained the examination in advance; among these, 72.1% indicated
      satisfaction with the explanation. A total of 21.8% and 20.5% indicated
      consulting the Internet, or friends and family, respectively, to learn about the
      examination. An overall understanding of the examination was reported by 70.8%. A
      total of 18.8% had unanswered questions about the examination, most commonly
      regarding examination logistics, contrast-agent usage, and when results would be
      available. A total of 52.9% were interested in discussing the examination with a
      radiologist in advance. Level of understanding was greatest for CT and least for
      nuclear medicine examinations, and lower when patients had not previously
      undergone the given examination. CONCLUSIONS: Patients' knowledge of their
      imaging examinations is frequently incomplete. The findings may motivate
      initiatives to improve patients' understanding of their imaging examinations,
      enhancing patient empowerment and contributing to patient-centered care.

PMID- 25868672
TI  - Genotype 1 of hepatitis C virus increases the risk of major depression: a 12-week
      prospective study.
AB  - OBJECTIVE: Depressive symptoms have been frequently observed in association with
      immune activation. We prospectively evaluate depressive symptoms and risk factors
      for major depression in patients with hepatitis C virus treated with antiviral
      combined therapy. METHODS: Fifty patients were assessed during 1 year; the
      structured diagnostic interview - Mini International Neuropsychiatric Interview -
      was used to screen psychiatric disorders at the baseline and during the 4th and
      12th week of antiviral therapy. STATISTICAL ANALYSIS: generalized estimating
      equations and pairwise comparisons with Bonferroni adjustment. RESULTS: In our
      sample the prevalence of the Genotype 1 was 42%, and the pegylated interferon
      alpha plus ribavirin was the most prevalent treatment used for hepatitis C (86%).
      We found increased risk of depression in the 4th week (34%) but not in the 12th
      week (24%) compared with baseline values (20%) (P=0.040). In addition, we found
      differences between depression prevalence and hepatitis C genotypes, with higher
      odds in the 4th week compared to the baseline and 12th week [OR: 2.1(1.15-2.9);
      P=0.040]. Patients with the Genotype 2/3 had significantly lower odds of
      presenting depression compared to the Genotype 1 [OR: 0.3 (0.1-0.9); P=0.030].
      CONCLUSION: This study provides evidence for an association between hepatitis C
      genotype and major depression, showing that besides immune activation, the
      Genotype 1 is associated with increased risk for psychiatric symptoms during the
      follow-up.

PMID- 25868673
TI  - Ubiquitous expression and multiple functions of biologically active peptides.
AB  - Biologically active peptides are widely expressed throughout in human bodies. For
      example, endothelin-1 and adrenomedullin are expressed in almost all types of
      cells, including neurons, glial cells, fibroblasts, macrophages, cardiomyocytes,
      vascular endothelial cells, epithelial cells and cancer cells of various origins.
      Expression of both these peptides is induced by stimuli, such as hypoxia and
      inflammatory cytokines. They have a variety of biological functions, such as
      effects on brain function, hormone secretion, the cardiovascular system and cell
      proliferation. By contrast, orexins (hypocretins) and melanin-concentrating
      hormone (MCH) are specifically expressed in the hypothalamus, particularly in the
      lateral hypothalamus, although very low concentrations of these peptides are
      found in the peripheral tissues. Orexins and MCH play coordinated, but distinct
      physiological roles in the regulation of sleep-wake cycle, appetite, emotion and
      other brain functions. The cardiovascular system is regulated by cardiovascular
      peptides, such as natriuretic peptides, endothelins and angiotensin II. The renin
      angiotensin system (RAS) is one of the most classical regulatory systems on blood
      pressure, electrolytes and kidney. (Pro)renin receptor is a novel member of the
      RAS and may be related to the pathophysiology of microvascular complications of
      hypertension and diabetes mellitus. Moreover, (pro)renin receptor forms a
      functional complex with vacuolar-type H(+)-ATPase, which plays an important
      physiological role in maintaining the acidic environment of intracellular
      compartments including secretory vesicles. Perhaps, the complex of (pro)renin
      receptor and vacuolar-type H(+)-ATPase may be important for the post
      translational processing and secretion of many biologically active peptides. 

PMID- 25868674
TI  - Planar and SPECT ventilation/perfusion imaging and computed tomography for the
      diagnosis of pulmonary embolism: A systematic review and meta-analysis of the
      literature, and cost and dose comparison.
AB  - Diagnosing acute pulmonary embolism (PE) is an indication for scintillation V/Q
      imaging (planar and SPECT) and/or CTPA. This study reviews, compares and
      aggregates the published diagnostic performance of each modality and assesses the
      short-term consequences in terms of diagnostic outcomes, monetary cost, and
      radiation burden. We performed a formal literature review of available data and
      aggregated the finding using a summary receiver operating characteristic. A
      decision tree approach was used to estimate cost and dose per correct diagnosis.
      The review found 19 studies, which comprised 27 data sets (6393 examinations,
      from 5923 patients). The results showed that planar V/Q was significantly
      inferior to both V/Q SPECT and CTPA with no difference between the latter two.
      CTPA represents best value; L129 per correct diagnosis compared to L243 (SPECT)
      and L226 (planar). In terms of radiation burden V/Q SPECT was the most effective
      with a dose of 2.12 mSv per correct diagnosis compared with 3.46 mSv (planar) and
      4.96 (CTPA) mSv. These findings show no performance difference between V/Q SPECT
      and CTPA; planar V/Q is inferior. CTPA is clearly the most cost effective
      technique. V/Q SPECT should be considered in situations where radiation dose is
      of concern or CTPA is inappropriate.

PMID- 25868677
TI  - Recent advances in medical device triage technologies for chemical, biological,
      radiological, and nuclear events.
AB  - In 2010, the US Food and Drug Administration (Silver Spring, Maryland USA)
      created the Medical Countermeasures Initiative with the mission of development
      and promoting medical countermeasures that would be needed to protect the nation
      from identified, high-priority chemical, biological, radiological, or nuclear
      (CBRN) threats and emerging infectious diseases. The aim of this review was to
      promote regulatory science research of medical devices and to analyze how the
      devices can be employed in different CBRN scenarios. Triage in CBRN scenarios
      presents unique challenges for first responders because the effects of CBRN
      agents and the clinical presentations of casualties at each triage stage can
      vary. The uniqueness of a CBRN event can render standard patient monitoring
      medical device and conventional triage algorithms ineffective. Despite the
      challenges, there have been recent advances in CBRN triage technology that
      include: novel technologies; mobile medical applications ("medical apps") for
      CBRN disasters; electronic triage tags, such as eTriage; diagnostic field
      devices, such as the Joint Biological Agent Identification System; and decision
      support systems, such as the Chemical Hazards Emergency Medical Management
      Intelligent Syndromes Tool (CHEMM-IST). Further research and medical device
      validation can help to advance prehospital triage technology for CBRN events.

PMID- 25868676
TI  - Goal- and retrieval-dependent activity in the striatum during memory recognition.
AB  - The striatum has been associated with successful memory retrieval but the precise
      functional link still remains unclear. One hypothesis is that striatal activity
      reflects an active evaluation process of the retrieval outcome dependent on the
      current behavioral goals rather than being a consequence of memory reactivation.
      We have recently shown that the striatum also correlates with confidence in
      memory recognition, which could reflect high subjective value ascribed to high
      certainty decisions. To examine whether striatal activity during memory
      recognition reflects subjective value indeed, we conducted an fMRI study using a
      recognition memory paradigm in which the participants rated not only the
      recognition confidence but also indicated the pleasantness associated with the
      previous memory retrieval. The results demonstrated a high positive correlation
      between confidence and pleasantness both on the behavioral and brain activation
      level particularly in the striatum. As almost all of variance in the striatal
      confidence signal could be explained by experienced pleasantness, this part of
      the striatal memory recognition response probably corresponds to greater
      subjective value of high confidence responses. While perceived oldness was also
      strongly correlated with striatal activity, this activation pattern was clearly
      distinct from that associated with confidence and pleasantness and thus could not
      be explained by higher subjective value to detect "old" items. Together, these
      results show that at least two independent processes contribute to striatal
      activation in recognition memory: a more flexible evaluation response dependent
      on context and goals captured by memory confidence and a potentially retrieval
      related response captured by perceived oldness. 

PMID- 25868675
TI  - Paraseptal emphysema: Prevalence and distribution on CT and association with
      interstitial lung abnormalities.
AB  - OBJECTIVE: To investigate the prevalence and distribution of paraseptal emphysema
      on chest CT images in the Framingham Heart Study (FHS) population, and assess its
      impact on pulmonary function. Also pursued was the association with interstitial
      lung abnormalities. MATERIALS AND METHODS: We assessed 2633 participants in the
      FHS for paraseptal emphysema on chest CT. Characteristics of the participants,
      including age, sex, smoking status, clinical symptoms, and results of pulmonary
      function tests, were compared between those with and without paraseptal
      emphysema. The association between paraseptal emphysema and interstitial lung
      abnormalities was investigated. RESULTS: Of the 2633 participants, 86 (3%) had
      pure paraseptal emphysema (defined as paraseptal emphysema with no other subtypes
      of emphysema other than paraseptal emphysema or a very few centrilobular
      emphysema involved) in at least one lung zone. The upper zone of the lungs was
      almost always involved. Compared to the participants without paraseptal
      emphysema, those with pure paraseptal emphysema were significantly older, and
      were more frequently male and smokers (mean 64 years, 71% male, mean 36 pack
      years, P<0.001) and had significantly decreased FEV1/FVC% (P=0.002), and
      diffusion capacity of carbon monoxide (DLCO) (P=0.002). There was a significant
      association between pure paraseptal emphysema and interstitial lung abnormalities
      (P<0.001). CONCLUSIONS: The prevalence of pure paraseptal emphysema was 3% in the
      FHS population, predominantly affects the upper lung zone, and contributes to
      decreased pulmonary function. Cigarette smoking, aging, and male gender were the
      factors associated with the presence of paraseptal emphysema. Significant
      association between paraseptal emphysema and interstitial lung abnormalities was
      observed.

PMID- 25868679
TI  - A tripeptide isolated from Bothrops atrox venom has neuroprotective and
      neurotrophic effects on a cellular model of Parkinson's disease.
AB  - Parkinson's disease (PD) is the second most common neurodegenerative disorder;
      however, there is no treatment able to prevent the loss of dopaminergic neurons
      or its consequences. Trophic factors such as NGF and BDNF has positive effects on
      different disorders of the brain, including neurodegeneration. Additionally,
      studies have suggested the use of venom peptides as a therapeutic strategy for
      neurological disorders. Therefore, in the present study, we investigated the
      neuroprotective activity of a peptide isolated from Bothrops atrox venom and its
      trophic ability by using a cellular model of dopaminergic neurotoxicity induced
      by 1-methyl-4-phenylpyridinium (MPP(+)) in PC12 cells. We showed that it
      decreased the activities of the apoptotic proteases caspase-9 (mitochondrial) and
      caspase-3 (executor) and increased cell viability and proliferation in this
      model. Additionally, it increased neuritogenesis in non-treated PC12 cells
      (neuronal model) as well as in PC12 cells treated with the dopaminergic
      neurotoxin. The amino acid sequence of the peptide was identified as Glutamic
      acid-Valine-Tryptophan (Glu-Val-Trp). These findings suggest that this tripeptide
      has the potential to protect against the dopaminergic neurons loss and that
      trophic stimulation of neuroplasticity might be involved in its mechanism of
      neuroprotection. 

PMID- 25868680
TI  - Novel and existing data for a future physiological toxicokinetic model of
      ethylene and its metabolite ethylene oxide in mouse, rat, and human.
AB  - The olefin ethylene is a ubiquitously found gas. It originates predominantly from
      plants, combustion processes and industrial sources. In mammals, inhaled ethylene
      is metabolized by cytochrome P450-dependent monooxygenases, particularly by
      cytochrome P450 2E1, to ethylene oxide, an epoxide that directly alkylates
      proteins and DNA. Ethylene oxide was mutagenic in vitro and in vivo in insects
      and mammals and carcinogenic in rats and mice. A physiological toxicokinetic
      model is a most useful tool for estimating the ethylene oxide burden in ethylene
      exposed rodents and humans. The only published physiological toxicokinetic model
      for ethylene and metabolically produced ethylene oxide is discussed.
      Additionally, existing data required for the development of a future model and
      for testing its predictive accuracy are reviewed and extended by new gas uptake
      studies with ethylene and ethylene oxide in B6C3F1 mice and with ethylene in F344
      rats. 

PMID- 25868681
TI  - Investigating dynamics and predictors of suicidal behaviors using ambulatory
      assessment.
AB  - Ambulatory assessment studies may provide important insights in the etiology of
      suicidal behaviors, because suicidal behaviors and their risk factors fluctuate
      over time.The review aims at (1) evaluating the current state of research and (2)
      summarizing main findings in this field. Reviewed studies (N = 4) were
      heterogeneous. Up to 74% of participants reported suicidal ideation during
      ambulatory assessment sampling. Suicidal ideation was predicted by intensity and
      instability of negative affective states (e.g., worry, sadness). Ambulatory
      assessment studies seem a promising approach to uncover the dynamic course of
      suicidal ideation and its risk factors in clinically relevant time frames (i.e.,
      real-time).

PMID- 25868682
TI  - [Psychoeducational Smoking Cessation Groups in an Acute Psychiatry Ward].
AB  - BACKGROUND: In view of the high prevalence of dependent smokers in psychiatric
      inpatient facilities advice for smoking cessation seems crucial. Due to the
      relatively short duration of stay in acute psychiatric wards (in our facility < 2
      weeks) there is a need for therapeutic concepts that link to outpatient settings.
      The transtheoretical model by "Prochaska and DiClemente" (TTM) seems suitable to
      create an appropriate therapeutic concept. METHODS: At the department of adult
      psychiatry located at Tulln university hospital, Austria, psychoeducational
      groups for smoking cessation were conducted. Apart from the degree of dependence
      using Fagerstrom test for nicotine-dependence (FTND), 100 mm visual analogue
      scales (VAS) were utilized to evaluate the patients' motivation for quitting
      smoking (100 VAS: maximimum motivation), the presenting physician (100 VAS: best
      performance), the content (100 VAS: best content) and the comprehensibility (100
      VAS: optimum understanding). RESULTS: Out of 37 participants, the majority (89.2
      %), showed a moderate to very strong nicotine dependence. The median motivation
      for smoking cessation was 56 VAS, the median change in motivation 67 VAS, the
      content 96 VAS, comprehensibility 94 VAS and presenter was rated with 95 VAS.
      CONCLUSIONS: In general, patients showed high levels of nicotine dependence. The
      psychoeducational group was predominantly evaluated in a positive way. Individual
      change in motivation to quit smoking might correspond to a stage in the TTM
      making a collaboration with outpatient facilities inevitable.

PMID- 25868683
TI  - [Prevalence and recognition of depression among inpatients of non-psychiatric
      hospital departments].
AB  - PURPOSE: The purpose of this study is to compare the prevalence of depression
      among different types of hospital departments. Furthermore, it compares different
      methods for assessment of its recognition by non-psychiatric physicians. METHODS:
      993 inpatients of internal, surgical, gynecological and physical rehabilitation
      wards of community hospitals were interviewed by research psychiatrists using the
      Clinical Interview Schedule. Ward physicians were asked to fill in a short
      questionnaire in order to assess whether they could correctly identify patients
      with mental illnesses. In addition, routine discharge diagnoses were assessed.
      RESULTS: Of the total sample, 13.3 % suffered from depression. Depression was
      most frequent on physical rehabilitation units (24.2 %), followed by surgical
      (9.8 %) and internal (9.5 %) wards. On gynecological wards, prevalence of
      depression was lowest (8.7 %). Of those suffering from depression, 45.7 % were
      identified as mentally ill by non-psychiatric ward physicians when using
      questionnaire data. Only 21.0 % of the depressed received a psychiatric discharge
      diagnosis, which equals less than half of those identified by questionnaire.
      RESULTS: Of the total sample, 13.3 % of patients suffered from depression.
      Depression was most frequent in physical rehabilitation units (24.2 %), followed
      by surgical (9.8 %) and internal (9.5 %) wards. In gynecological wards, the
      prevalence of depression was the lowest (8.7 %). Of those suffering from
      depression, 45.7 % were identified as mentally ill by non-psychiatric ward
      physicians when using questionnaire data. Only 21.0 % of the depressed received a
      psychiatric discharge diagnosis, less than half of those identified by the
      questionnaire. CONCLUSIONS: Depression is very common among inpatients of
      physical hospital departments. Unfortunately, depression is frequently overlooked
      in everyday clinical work. Routine discharge diagnoses give only very limited
      information about how often ward physicians recognize mental disorders.
      Furthermore, hospital discharge diagnoses should not be used for planning mental
      health services.

PMID- 25868684
TI  - Nitrogen cycling in corals: the key to understanding holobiont functioning?
AB  - Corals are animals that form close mutualistic associations with endosymbiotic
      photosynthetic algae of the genus Symbiodinium. Together they provide the calcium
      carbonate framework of coral reef ecosystems. The importance of the microbiome
      (i.e., bacteria, archaea, fungi, and viruses) to holobiont functioning has only
      recently been recognized. Given that growth and density of Symbiodinium within
      the coral host is highly dependent on nitrogen availability, nitrogen-cycling
      microbes may be of fundamental importance to the stability of the coral-algae
      symbiosis and holobiont functioning, in particular under nutrient-enriched and 
      depleted scenarios. We summarize what is known about nitrogen cycling in corals
      and conclude that disturbance of microbial nitrogen cycling may be tightly linked
      to coral bleaching and disease. 

PMID- 25868685
TI  - Consumer Attitudes and Perceptions on mHealth Privacy and Security: Findings From
      a Mixed-Methods Study.
AB  - This study examined consumers' attitudes and perceptions regarding mobile health
      (mHealth) technology use in health care. Twenty-four focus groups with 256
      participants were conducted in 5 geographically diverse locations. Participants
      were also diverse in age, education, race/ethnicity, gender, and rural versus
      urban settings. Several key themes emerged from the focus groups. Findings
      suggest that consumer attitudes regarding mHealth privacy/security are highly
      contextualized, with concerns depending on the type of information being
      communicated, where and when the information is being accessed, who is accessing
      or seeing the information, and for what reasons. Consumers frequently considered
      the tradeoffs between the privacy/security of using mHealth technologies and the
      potential benefits. Having control over mHealth privacy/security features and
      trust in providers were important issues for consumers. Overall, this study found
      significant diversity in attitudes regarding mHealth privacy/security both within
      and between traditional demographic groups. Thus, to address consumers' concerns
      regarding mHealth privacy and security, a one-size-fits-all approach may not be
      adequate. Health care providers and technology developers should consider
      tailoring mHealth technology according to how various types of information are
      communicated in the health care setting, as well as according to the comfort,
      skills, and concerns individuals may have with mHealth technology. 

PMID- 25868686
TI  - Probing long-range carrier-pair spin-spin interactions in a conjugated polymer by
      detuning of electrically detected spin beating.
AB  - Weakly coupled electron spin pairs that experience weak spin-orbit interaction
      can control electronic transitions in molecular and solid-state systems. Known to
      determine radical pair reactions, they have been invoked to explain phenomena
      ranging from avian magnetoreception to spin-dependent charge-carrier
      recombination and transport. Spin pairs exhibit persistent spin coherence,
      allowing minute magnetic fields to perturb spin precession and thus recombination
      rates and photoreaction yields, giving rise to a range of magneto-optoelectronic
      effects in devices. Little is known, however, about interparticle magnetic
      interactions within such pairs. Here we present pulsed electrically detected
      electron spin resonance experiments on poly(styrene-sulfonate)-doped poly(3,4
      ethylenedioxythiophene) ( PEDOT: PSS) devices, which show how interparticle spin
      spin interactions (magnetic-dipolar and spin-exchange) between charge-carrier
      spin pairs can be probed through the detuning of spin-Rabi oscillations. The
      deviation from uncoupled precession frequencies quantifies both the exchange (<30
      neV) and dipolar (23.5+/-1.5 neV) interaction energies responsible for the pair's
      zero-field splitting, implying quantum mechanical entanglement of charge-carrier
      spins over distances of 2.1+/-0.1 nm.

PMID- 25868688
TI  - Theoretical and experimental investigation of crown/ammonium complexes in
      solution.
AB  - The Gibbs energies of association DeltaGsolT between primary alkyl ammonium ions
      and crown ethers in solution are measured and calculated. Measurements are
      performed by isothermal titration calorimetry and revealed a strong solvent
      dependent ion pair effect. Calculations are performed with density functional
      theory including Grimme's dispersion correction D3(BJ). The translational,
      rotational, and vibrational contributions to the Gibbs energy of association
      DeltaGsolT are taken into account by a rigid-rotor-harmonic-oscillator
      approximation with a free-rotor approximation for low lying vibrational modes.
      Solvation effects deltaGseT are taken into account by applying the continuum
      solvation model COSMO-RS. Our study aims at finding a suitable theoretical method
      for the evaluation of the host guest interaction in crown/ammonium complexes as
      well as the observed ion pair effects. A good agreement of theory and experiment
      is only achieved, when solvation and the effects of the counterions are
      explicitly taken into account. 

PMID- 25868687
TI  - Depression after minor stroke: Prevalence and predictors.
AB  - OBJECTIVE: Severity of stroke and disability after stroke are major predictors of
      post-stroke depression (PSD). The prevalence of PSD in patients with minor stroke
      is expected to be low because minor stroke is characterized by mild neurological
      dysfunction. The aim of this study was to investigate the prevalence and
      predictors of PSD in patients with minor ischemic stroke. METHODS: Patients with
      first-ever minor ischemic stroke (n=757) were followed up at 14+/-2 days, 3
      months, 6 months, and 1year after stroke. Depression status was assessed at each
      follow-up. Patients that had PSD at follow-ups were classified into two groups
      according to the time point of the diagnosis of PSD: patients diagnosed at 14+/-2
      days formed the early-onset PSD group, and those who were diagnosed at any
      subsequent follow-ups constituted the late-onset PSD group. RESULTS: The 1-year
      prevalence of PSD in patients with minor stroke was 29.0% (95% CI, 25.2-32.8).
      Female gender, current smoking at stroke onset, mild global cognitive impairment
      at 14+/-2 days, and stroke recurrence were independently associated with a high
      risk of PSD over the 1-year follow-up. Predictors of early-onset PSD included
      female gender, current smoking, and mild global cognitive impairment at 14+/-2
      days, while predictors of late-onset PSD were current smoking and stroke
      recurrence. CONCLUSION: Approximately three in ten patients with first-ever minor
      ischemic stroke may develop depression during the first year after stroke. Female
      gender, smoking, mild global cognitive impairment, and stroke recurrence predict
      early-onset or late-onset PSD after minor ischemic stroke.

PMID- 25868689
TI  - Multicarotenoids at Physiological Levels Inhibit Metastasis in Human
      Hepatocarcinoma SK-Hep-1 Cells.
AB  - Several studies have demonstrated that single carotenoid, including lycopene,
      beta-carotene, and alpha-carotene, exhibits antimetastatic effects; however,
      little is known whether multicarotenoids have similar effects. Herein, we
      investigated the antimetastatic effect of multicarotenoids at physiological serum
      levels in Taiwanese (MCT at 1.4 MUM) and American (MCA at 1.8 MUM) populations
      using human hepatocarcinoma SK-Hep-1 cells in comparison with single carotenoid,
      such as lycopene (0.3 or 0.6 MUM, respectively), alpha-carotene (0.1 MUM), beta
      carotene (0.4 MUM), lutein (0.4 or 0.5 MUM, respectively), and beta-cryptoxanthin
      (0.2 MUM). Results reveal that MCA treatment exhibited an additive inhibition on
      invasion, migration and adhesion at 24 and 48 h of incubation, whereas MCT
      treatment possessed additive inhibition at 48 h of incubation. The antimetastatic
      action of MCT and MCA involved additive reduction on activities of matrix
      metalloproteinase (MMP)-2, -9, and protein expression of Rho and Rac 1 but
      additive promotion on protein expression of tissue inhibitor of MMP (TIMP)-1 and 
      2. All of these effects were stronger in MCA than in MCT at 24 and 48 h of
      incubation. These results demonstrate that multi-carotenoids effectively inhibit
      metastasis of human hepatocarcinoma SK-Hep-1 cells. More in vivo studies are
      needed to confirm these findings.

PMID- 25868691
TI  - Changing roles.

PMID- 25868690
TI  - LiTFSI in 1-butyl-1-methylpyrrolidinium bis(fluorosulfonyl)amide: a possible
      electrolyte for ionic liquid based lithium ion batteries.
AB  - In this communication, we show that the combination of 1 M lithium
      bis(trifluoromethylsulfonyl)amide and 1-butyl-1-methylpyrrolidinium
      bis(fluorosulfonyl)amide (LiTFSI/[Py1,4]FSI) can be regarded as a possible stable
      electrolyte for IL based lithium ion batteries. We compare the charge-discharge
      results with the electrolyte 1 M LiTFSI in 1-butyl-1-methylpyrrolidinium
      bis(trifluoromethylsulfonyl)amide ([Py1,4]TFSI) on an electrodeposited Ge
      electrode and show using a charge-discharge analysis and Raman spectroscopy that
      1 M LiTFSI/[Py1,4]FSI is advantageous in maintaining the charge capacity as well
      as electrolyte stability at high current densities. 

PMID- 25868692
TI  - Does England need a new genesis of forensic nursing?
AB  - This article begins by providing a global picture of violence and the possible
      effects it is having on the development worldwide of the forensic nurse examiner.
      A debate follows as to where the boundaries of this advancing nursing practice
      should lie in conjunction with medicine and postulates where this evolution in
      nursing may or may not be an advantage to the world of forensics. An analysis is
      then presented concerning violence in England and whether a need exists for
      registered nurses to expand and advance their practices, as already developed in
      other countries, in order to assist in civil, coronial, and crime investigations.
      This article closes by putting forward implications for nursing practice in
      England, the consequent multiprofessional issues that need to be debated to
      ensure that any such developments are not detrimental to legal investigations and
      health care, and recommendations for future needed research. 

PMID- 25868693
TI  - How long does it take a static speaking individual to contaminate the immediate
      environment?
AB  - Developments in forensic genetic profiling mean that only a very little DNA is
      required to generate an identifying profile. However, as this sensitivity
      increases so does the risk of contamination with non-offender DNA, potentially
      leading to the conviction of innocents, or release of the guilty. The work of
      Rutty et al. showed that a static and talking person deposited DNA in front of
      them within a 15-minute period. This work expands on that of Rutty et al. by
      determining the time period required for an individual to deposit sufficient DNA
      for a positive identification to be made, and the distance that this
      contamination can be detected from the speaking individual. To simulate a scene
      of crime, sheets of Benchkote((r)) were used to represent an area of interest and
      an unprotected subject talked over them for a variety of times, in a variety of
      positions (standing, kneeling, and sitting at a desk). Results show that
      contamination by talking in both kneeling and sitting positions occurred almost
      immediately (<30 seconds, but not from just one sentence) up to 69 cm from the
      subject. When standing, contamination could be observed up to a maximum 115 cm
      from the subject, and was only present in one of three repeats when talking for
      only 30 seconds. This article illustrates how rapidly a static person can
      potentially contaminate an area in front of him or herself within a laboratory or
      scene environment, just by talking. 

PMID- 25868694
TI  - Vertebrate species profiling in one step using a single primer.
AB  - Current species profiling techniques usually require several steps to identify an
      unknown species in quarantine cases and other forensic applications. Here we have
      developed a species profiling test that produces unique profiles for all
      vertebrate species tested using a single primer in a polymerase chain reaction.
      Samples tested included a range of mammals and other vertebrates such as fish and
      marsupials; a group of animals yet to be characterized with molecular speciation
      techniques. Species-specific profiles were shown to be reproducible and able to
      be generated from less than 10 ng of total DNA, comparable to DNA quantities used
      in conventional species profiling techniques. A case study demonstrates the
      utility of the technique by distinguishing between commercial and protected
      species of the Macropodidae (kangaroo) superfamily. 

PMID- 25868695
TI  - Chlamydial heat-shock protein 60 : A marker for chronic infection with Chlamydia
      Pneumoniae in atherosclerosis: Investigation of atherosclerotic coronary arteries
      by immunocytochemistry.
AB  - Worldwide, ischemic heart disease is an important cause of death and there is an
      increasing number of pointers toward a causative connection between Chlamydia
      pneumoniae and atherosclerosis. The presence, localization, and relationship to
      atheroma of Chlamydial heat-shock protein 60 (cHsp60) in coronary tissue was
      investigated by immunocytochemical methods and by different investigators. In the
      present study, for the first time, arterial segments, including the whole course
      of the great coronary arteries from proximal to distal, were investigated by
      immunocytochemistry to detect cHsp60. Specimens from coronary arteries of 46
      autopsy cases (17 females, 29 males; mean age: 62.7 years, SD 17.9 years) were
      examined (480 paraffin-embedded samples; 11 sites from each case). Different
      fixatives were used for the specimens taken at autopsy. Immunocytochemical
      staining was done using an anti-cHsp60 antibody (Affinity Bioreagents Inc.) and a
      modified Labeled-Strept-Avidine-Biotin-staining protocol (DAKO). The localization
      of signals by site of predilection in the course of coronary vessels and by
      coincidence with specific structural characteristics, was detected by light
      microscopy. Detection of cHsp60 was possible in 30 of 46 (65.2%) individuals
      (minimum one sample) and in 87 of 480 specimens (18.1%). The distribution of the
      signals was correlated to the intensity of atherosclerosis (mild to middle) and a
      decreasing frequency from proximal to distal arterial segments was found.
      Macroscopically, nonatherosclerotic vessels presented cHsp60 only occasionally.
      In accordance with recent publications, cHsp60 was detected in foam cells and
      macrophages, cell-poor regions, and thickened intimal layers, and more rarely in
      inflammatory infiltrates and calcified areas. According to previous studies, a
      distribution independent from atherosclerotic lesions was not found. Detection of
      cHsp60 was superior using Notox((r)) (Earth Industries) as a fixative in
      comparison with buffered formaldehyde. 

PMID- 25868696
TI  - A blind accuracy assessment of computer-modeled forensic facial reconstruction
      using computed tomography data from live subjects.
AB  - A computer modeling system for facial reconstruction has been developed that
      employs a touch-based application to create anatomically accurate facial models
      focusing on skeletal detail. This article discusses the advantages and
      disadvantages of the system and illustrates its accuracy and reliability with a
      blind study using computed tomography (CT) data of living individuals. Three
      dimensional models of the skulls of two white North American adults (one male,
      one female) were imported into the computer system. Facial reconstructions were
      produced by two practitioners following the Manchester method. Two posters were
      produced, each including a face pool of five surface model images and the facial
      reconstruction. The face pool related to the sex, age, and ethnic group of the
      target individual and included the surface model image of the target individual.
      Fifty-two volunteers were asked to choose the face from the face pool that most
      resembled each reconstruction. Both reconstructions received majority percentage
      hit rates that were at least 50% greater than any other face in the pool. The
      combined percentage hit rate was 50% above chance (70%). A quantitative
      comparison of the facial morphology between the facial reconstructions and the CT
      scan models of the subjects was carried out using Rapidform(TM) 2004 PP2-RF4. The
      majority of the surfaces of the facial reconstructions showed less than 2.5 mm
      error and 90% of the male face and 75% of the female face showed less than 5 mm
      error. Many of the differences between the facial reconstructions and the facial
      scans were probably the result of positional effects caused during the CT
      scanning procedure, especially on the female subject who had a fatter face than
      the male subject. The areas of most facial reconstruction error were at the ears
      and nasal tip. 

PMID- 25868697
TI  - Sudden natural death in a suicide attempt.
AB  - In this article, we report an unusual case of sudden death arising from a
      ruptured basilar artery aneurysm during a suicide attempt. A 72-year-old male was
      found dead in his home after sustaining superficial flesh gunshot wounds (entrace
      and exit) involving the forehead. The victim had been depressed for several
      months and had frank suicide intention. The pertinent autopsy findings revealed a
      superficial nonpenetrating bullet path of the scalp with no skull fractures or
      brain injuries. However, brain examination identified subrachnoid hemorrhage and
      subdural clot about the brainstem and within the posterior fossa, linked to a
      basilar artery aneourysm rupture. The cause and manner of death and contributing
      factors of the "non-lethal" gunshot wounds are discussed. 

PMID- 25868698
TI  - Detection of colchicine by means of LC-MS/MS after mistaking meadow saffron for
      bear's garlic.
AB  - The accidental ingestion of plant material containing colchicines is a rare cause
      of lethal poisoning. The death of a married couple who mistook colchicines for
      Bear's garlic (Allium ursinum) and prepared the latter as a salad is the tragic
      topic of this article. After discussing the specificity of the histological
      findings, a chemicotoxicological method using liquid chromatographic mass
      spectrometric (LC-MS/MS) is presented. Toxicological analyses using LC-MS/MS
      revealed colchicine concentrations between 36.6 ng/mL and 98.3 ng/mL in the heart
      blood and between 22.7 ng/mL and 78.4 ng/mL in the femoral blood of the victims. 

PMID- 25868699
TI  - Sudden, unexpected death resulting from a giant coronary artery aneurysm.
AB  - Aneurysms of the coronary arteries are rare and most cases develop in vessels
      with severe atherosclerosis. However, coronary aneurysms of other etiological
      origins may occur in younger people. These cases often remain undetected until a
      sudden and sometimes fatal complication occurs. Therefore, knowledge of the
      disease is important not only for the clinician, but also for the forensic
      pathologist. We report the case of a young man who died suddenly and unexpectedly
      and in whom autopsy revealed a giant coronary artery aneurysm complicated by
      fresh, obliterating thrombosis. 

PMID- 25868700
TI  - Disaster victim identification.
AB  - In the event of any mass fatality incident, despite the cause, disaster victim
      identification must be undertaken; the humanitarian and legal responsibility for
      this falls on the forensic community. Mass fatality incidents can be natural
      (e.g., tsunamis, earthquakes, hurricanes), accidental (e.g., building collapse,
      ship sinking) or can occur as a result of a terrorist attack. Terrorism alone has
      been responsible for thousands of deaths in recent years and can be encountered
      in many forms (e.g., suicide bombings, airplane hijackings). In mass fatality
      situations, the experitise of many specialities are called on to assist in the
      identification efforts and to allow for the speedy return of recovered human
      remains to the relatives of the deceased. Today, DNA plays a vital but never
      solitary role in disaster victim identification. 

PMID- 25868701
TI  - Fatal consequence of short-term benzodiazepine administration followed by proton
      pump-inhibitor therapy.

PMID- 25868702
TI  - Ba'alat.

PMID- 25868703
TI  - Erratum to: Bayes optimal template matching for spike sorting - combining fisher
      discriminant analysis with optimal filtering.

PMID- 25868704
TI  - Bootstrap testing for cross-correlation under low firing activity.
AB  - A new cross-correlation synchrony index for neural activity is proposed. The
      index is based on the integration of the kernel estimation of the cross
      correlation function. It is used to test for the dynamic synchronization levels
      of spontaneous neural activity under two induced brain states: sleep-like and
      awake-like. Two bootstrap resampling plans are proposed to approximate the
      distribution of the test statistics. The results of the first bootstrap method
      indicate that it is useful to discern significant differences in the
      synchronization dynamics of brain states characterized by a neural activity with
      low firing rate. The second bootstrap method is useful to unveil subtle
      differences in the synchronization levels of the awake-like state, depending on
      the activation pathway. 

PMID- 25868705
TI  - Patients characteristics influencing the longitudinal utilization of steroids in
      multiple sclerosis--an observational study.
AB  - BACKGROUND: Multiple Sclerosis is the most common disease in young adults
      affecting the central nervous system. Disease may progress with acute attacks
      (relapsing MS) or continuously (progressive MS). Glucocorticosteroids are used in
      the treatment of acute attacks. The aim of this study was to analyse
      characteristics of patients with MS, and their influence on current treatment
      patterns of relapses with glucocorticosteroids. DESIGN: In 2001, the German
      National MS Society initiated the German MS-Registry. Patients with relapsing MS
      were included (n = 5106) from this registry. Logistic regression models were used
      to detect trends over time. The likelihood of administration of steroids is
      modelled in dependence of calendar year and in dependence to confounders in
      treatment conditions. The sample size allows that odds ratios can be detected
      with a power of 90% (alpha = 0.05). RESULTS: Administration of
      glucocorticosteroids was influenced by EDSS (P < 0.0001), age (P < 0.0001) and
      disease duration (P < 0.0001). Therapy administration in an outpatient setting
      was more likely in patients with higher EDSS (P < 0.0001) and longer disease
      duration (P < 0.0001). The utilization of glucocorticosteroids increased with
      higher EDSS for all relapsing patients. Interestingly, all overutilization of
      glucocorticosteroids decreased over time and was accompanied by a steadily
      increased administration of emergent therapeutics. Although there are about 70%
      of registered patients with relapsing MS on immune-modulatory treatment, almost
      60% of them received glucocorticosteroids for treatment of relapses. CONCLUSIONS:
      Treatment patterns with glucocorticosteroids in patients with MS are influenced
      mainly by EDSS and disease duration. The decline in the utilization of
      glucocorticosteroids is accompanied by an increase in natalizumab treatment.

PMID- 25868706
TI  - Radioimmunotherapy ((90) Y-Ibritumomab Tiuxetan) for Posttransplant
      Lymphoproliferative Disorders After Prior Exposure to Rituximab.
AB  - Posttransplantation lymphoproliferative disorders (PTLDs) are life-threatening
      complications after solid organ and hematopoietic stem cell transplantation. Only
      half of CD20-positive PTLDs respond to rituximab monotherapy, and outcomes remain
      poor for patients with relapsed/refractory disease, especially those who do not
      qualify for an anthracycline containing regimen due to frailty or comorbidities.
      Radioimmunotherapy (RIT) might be an option in this particular setting. We report
      a panel of eight patients with rituximab refractory/relapsed CD20-positive PTLDs
      including three ineligible for subsequent CHOP-like chemotherapy who received
      (90) Y-Ibritumomab tiuxetan as a single agent (n = 7) or combined to chemotherapy
      (n = 1). Five out of eight patients were kidney transplant recipients, while 2/8
      had a liver transplant and 1/8 had a heart transplant. Patients received a median
      of two previous therapies. Overall response rate was 62.5%. Importantly, all
      responders achieved complete response. At a median follow-up of 37 months [5;
      84], complete response was ongoing in four patients. Toxicity was predominantly
      hematological and easily manageable. No graft rejection was noticed concomitantly
      or following RIT administration despite immunosuppression reduction after
      diagnosis of PTLDs. This report emphasizes the potential efficiency of salvage
      RIT for early rituximab refractory PTLDs without any unexpected toxicity.

PMID- 25868707
TI  - Engineering the bacterial shapes for enhanced inclusion bodies accumulation.
AB  - Many bacteria can accumulate inclusion bodies such as sulfur, polyphosphate,
      glycogen, proteins or polyhydroxyalkanoates. To exploit bacteria as factories for
      effective production of inclusion bodies, a larger intracellular space is needed
      for more inclusion body accumulation. In this study, polyhydroxybutyrate (PHB)
      was investigated as an inclusion bodies representative to be accumulated by
      Escherichia coli JM109SG. Various approaches were taken to increase the bacterial
      cell sizes including deletion on actin-like protein gene mreB, weak expression of
      mreB in mreB deletion mutant, and weak expression of mreB in mreB deletion mutant
      under inducible expression of SulA, the inhibitor of division ring protein FtsZ.
      All of the methods resulted in different levels of increases in bacterial sizes
      and PHB granules accumulation. Remarkably, an increase of over 100% PHB
      accumulation was observed in recombinant E. coli overexpressing mreB in an mreB
      deletion mutant under inducible expression of FtsZ inhibiting protein SulA. The
      molecular mechanism of enlarged bacterial size was found to be directly relate to
      weakened cytoskeleton which was the result of broken skeleton helix. 

PMID- 25868708
TI  - Transcriptional regulation of tenascin-W by TGF-beta signaling in the bone
      metastatic niche of breast cancer cells.
AB  - Tenascin-W is a matricellular protein with a dynamically changing expression
      pattern in development and disease. In adults, tenascin-W is mostly restricted to
      stem cell niches, and is also expressed in the stroma of solid cancers. Here, we
      analyzed its expression in the bone microenvironment of breast cancer metastasis.
      Osteoblasts were isolated from tumor-free or tumor-bearing bones of mice injected
      with MDA-MB231-1833 breast cancer cells. We found a fourfold upregulation of
      tenascin-W in the osteoblast population of tumor-bearing mice compared to healthy
      mice, indicating that tenascin-W is supplied by the bone metastatic niche.
      Transwell and co-culture studies showed that human bone marrow stromal cells
      (BMSCs) express tenascin-W protein after exposure to factors secreted by MDA
      MB231-1833 breast cancer cells. To study tenascin-W gene regulation, we
      identified and analyzed the tenascin-W promoter as well as three evolutionary
      conserved regions in the first intron. 5'RACE analysis of mRNA from human breast
      cancer, glioblastoma and bone tissue showed a single tenascin-W transcript with a
      transcription start site at a noncoding first exon followed by exon 2 containing
      the ATG translation start. Site-directed mutagenesis of a SMAD4-binding element
      in proximity of the TATA box strongly impaired promoter activity. TGFbeta1
      induced tenascin-W expression in human BMSCs through activation of the TGFbeta1
      receptor ALK5, while glucocorticoids were inhibitory. Our experiments show that
      tenascin-W acts as a niche component for breast cancer metastasis to bone by
      supporting cell migration and cell proliferation of the cancer cells. 

PMID- 25868709
TI  - Thermal processing of bone: in vitro response of mesenchymal cells to bone
      conditioned medium.
AB  - The autoclaving, pasteurization, and freezing of bone grafts to remove bacteria
      and viruses, and for preservation, respectively, is considered to alter
      biological properties during graft consolidation. Fresh bone grafts release
      paracrine-like signals that are considered to support tissue regeneration.
      However, the impact of the autoclaving, pasteurization, and freezing of bone
      grafts on paracrine signals remains unknown. Therefore, conditioned medium was
      prepared from porcine cortical bone chips that had undergone thermal processing.
      The biological properties of the bone-conditioned medium were assessed by
      examining the changes in expression of target genes in oral fibroblasts. The data
      showed that conditioned medium obtained from bone chips that had undergone
      pasteurization and freezing changed the expression of adrenomedullin, pentraxin
      3, BTB/POZ domain-containing protein 11, interleukin 11, NADPH oxidase 4, and
      proteoglycan 4 by at least five-fold in oral fibroblasts. Bone-conditioned medium
      obtained from autoclaved bone chips, however, failed to change the expression of
      the respective genes. Also, when bone-conditioned medium was prepared from fresh
      bone chips, autoclaving blocked the capacity of bone-conditioned medium to
      modulate gene expression. These in vitro results suggest that pasteurization and
      freezing of bone grafts preserve the release of biologically active paracrine
      signals, but autoclaving does not. 

PMID- 25868710
TI  - Ketotifen use in a patient with fire ant hypersensitivity and mast cell
      activation syndrome.

PMID- 25868711
TI  - Black and Hispanic perceptions of asthma medication in the School Inner-City
      Asthma Study.

PMID- 25868712
TI  - Pregabalin for chronic pain: does one medication fit all?
AB  - BACKGROUND: Pregabalin is frequently prescribed for chronic non-cancer pain. No
      previous study has examined its off-label use. OBJECTIVES: Our primary aim was to
      assess the proportion of patients taking pregabalin for conditions approved by
      Health Canada ('on-label') and compare their perspectives on its use to those who
      use pregabalin for other conditions ('off-label'). METHODS: Patients who have
      used pregabalin within the past year were recruited from two registries of
      chronic non-cancer pain patients treated in tertiary care clinics: the Quebec
      Pain Registry and the Fibromyalgia Patients Registry. Data on the use of
      pregabalin and its perceived benefits were collected from the registries and from
      completed questionnaires. RESULTS: Out of 4339 screened chronic non-cancer pain
      patients, 355 (8.18%) met the study selection criteria. Three-quarters of them
      (268/355) used pregabalin for pain conditions not approved by Health Canada and
      were therefore regarded as off-label users. The most prevalent condition for
      pregabalin use was lumbar back pain (103/357; 28.85%). There were no significant
      differences between on- and off-label users in their perceived satisfaction from
      pregabalin therapy and its effect on function and quality of life. Among former
      users, the most prevalent reason for discontinuation was adverse effects, mainly
      dry mouth and weight gain. CONCLUSIONS: We conclude that despite specific
      indications for pregabalin prescription, it is mainly used off-label, notably for
      low back pain. Nevertheless, off-label users were equally satisfied with its
      clinical effects. Although formal exploration of the broader analgesic properties
      of pregabalin is warranted, treating heterogeneous chronic pain conditions with
      pregabalin may be legitimate. LIMITATIONS: The main limitations of the study are
      patients' low response rate, the recruitment of participants solely from a
      tertiary pain center and not from the general patient population and a possible
      recall bias that may have arisen from the retrospective nature of the study.

PMID- 25868713
TI  - Production of polyunsaturated fatty acids in recombinant Lipomyces starkeyi
      through submerged fermentation.
AB  - Long chain polyunsaturated fatty acids (LCPUFA) are known to play an important
      role in human health and nutrition. Considering the limitation of LCPUFA sources,
      it is necessary to search new avenues for their production. Oleaginous yeasts are
      an attractive target for harvesting single cell oil, mainly because of the ease
      of cultivation with cheaper raw material. Lipomyces starkeyi is one such
      oleaginous yeast, which can accumulate oil to the extent of 60% of its biomass
      and where genetic transformation can be achieved. In our earlier work, Delta15
      desaturase gene (AEP37840) from flax was transformed into L. starkeyi. In the
      present work, we report optimization of medium for the production of omega-3
      enriched oil from this transformed yeast. A basic medium containing 20 g/l
      glucose as a carbon source and 10 g/l yeast extract as a nitrogen source was used
      during fermentation. At regular time intervals, glucose was fed to maintain high
      C:N ratio (65:10) during fermentation. Under the most favorable conditions, dry
      biomass and total lipid content were 18 and 7.29 g/l, respectively. Prior to
      genetic transformation, L. starkeyi contained 56.03 mg/l DHA along with 71.4 mg/l
      EPA and 42.2 mg/l ALA. Genetic engineering of this yeast resulted in a strain
      that produced 1080 mg/l DHA (17.4%) along with 74.28 mg/l EPA and 126.72 mg/l ALA
      possibly through modification of PUFA biosynthetic pathway. To the best of our
      knowledge, this is a first report of DHA enrichment and opens up avenues for
      LCPUFA production through L. starkeyi.

PMID- 25868714
TI  - Numberical simulation of fluid flow and three-dimensional expansion of tissue
      engineering seed cells in large scale inside a novel rotating wall hollow fiber
      membrane bioreactor.
AB  - Currently, RWVB (Rotating wall vessel bioreactor) combined with a microcarrier
      used for in vitro expansion revealed that the suspended cells attached on the
      microcarrier will collide with outer and inner cylinders of RWVB inevitably,
      which leads to harmful results to the cells. Considering this, hollow fiber (HF)
      membrane module treated as a cell carrier is adopted to combine with RWVB to form
      a novel rotating wall hollow fiber membrane bioreactor (RWHMB) to avoid
      aforementioned harmful collision, since the cells cultured inside this bioreactor
      will mainly adhere to large specific surface of hollow fiber membrane module.
      Prior to cell experiment, mathematical simulations concerned with flow field
      inside RWHMB are performed by CFD, which includes the distributions of the total
      pressure, velocity, and shear stress with the variation of rotating speeds and
      directions, as well as the radial location and diameter of hollow fiber membrane.
      To further confirm the feasible parameters getting from the simulation, this
      RWHMB is adopted to expand osteoblasts isolated from SD rats within its dynamic
      conditions. Cell expansion in T-flask is carried out as a negative control. The
      results showed that with the same rotating direction and speed of 10 rpm, inner
      and outer cylinders of RWHMB generated cyclical stress stimulus, which was
      acceptable to cell expansion and facilitated the secretion of extracellular
      matrix. Besides, hollow fiber membrane carrier with a diameter of 0.2 mm has an
      excellent biocompatibility and their radial locations presented a tiny influence
      on flow field inside the culture chamber. 

PMID- 25868715
TI  - Studies on light intensity distribution inside an open pond photo-bioreactor.
AB  - Light intensity profiles inside an open tank were studied using ANSYS Fluent.
      Experiments were performed by taking Scenedesmus arcuatus, green microalgae at
      three different concentrations under actual sunlight conditions. Absorption of
      light intensity at different depths was measured experimentally. The results
      generated from CFD simulations were compared with the experimental results and
      the cornet model. It has been found that there is a good agreement between the
      light intensity profile obtained from the CFD simulation and that calculated
      using the Cornet's model. Light intensity profiles at different depths were
      calculated using CFD simulation by varying the dimensions of the tank. The effect
      of wall reflectivity, diffuse fraction and scattering phase function on light
      profile in side open tank are also studied using CFD simulation. 

PMID- 25868716
TI  - Freedom from local and regional failure of contralateral neck with ipsilateral
      neck radiotherapy for node-positive tonsil cancer: updated results of an
      institutional clinical management approach.
AB  - PURPOSE: To update the outcomes of an institutional clinical management approach
      using ipsilateral neck radiotherapy in the treatment of node-positive squamous
      cell carcinoma of the tonsil with a well-lateralized primary lesion. METHODS AND
      MATERIALS: Between August 2003 and April 2014, 61 consecutive patients with
      ipsilateral node-positive squamous cell carcinoma of the tonsil without
      involvement of the base of the tongue or midline soft palate were treated at a
      community hospital-based cancer center with radiotherapy to the primary site and
      ipsilateral neck. Overall survival, disease-free survival and freedom from
      contralateral failure were calculated. RESULTS: Median follow up was 37.2months
      (range 4-121months). Freedom from contralateral nodal failure at 5years was 98%
      with one contralateral nodal failure noted. The patient underwent a salvage neck
      dissection and was treated with post-operative radiotherapy with no evidence of
      disease to date. 5-year overall survival (OS) was 92.4% and 5year disease-free
      survival (DFS) was 86.7%. CONCLUSIONS: This represents the single largest series
      reported from a community hospital-based cancer center in which lateralized
      tonsil cancers with N+ disease were treated with ipsilateral neck radiotherapy.
      In this carefully selected cohort of patients with well-lateralized tonsil
      cancers, the risk of contralateral nodal failure appears to be <5%, suggesting
      that prophylactic radiation of the contralateral neck may not be necessary.
      Future planned studies will focus on prospectively selecting subgroups of
      patients eligible for treatment de-intensification as survivorship issues in
      excellent prognosis HPV positive patients are increasingly becoming relevant.

PMID- 25868717
TI  - Chemoprevention targets for tobacco-related head and neck cancer: past lessons
      and future directions.
AB  - Progress toward identifying an effective chemopreventive agent to reduce the
      incidence of head and neck squamous cell carcinoma (HNSCC) has been limited by
      poor efficacy and intolerable toxicity profiles. In this review, we summarize the
      biological basis of HNSCC chemoprevention, and outline challenges associated with
      identifying appropriate high-risk HNSCC populations for chemoprevention studies.
      We discuss findings and lessons learned from clinical trials that have
      investigated micronutrient and molecular targeting interventions. Finally, we
      introduce the concept of green chemoprevention, interventions based upon whole
      plant foods or simple extracts that may represent a safe and cost-conscious
      option for the next generation of studies. As our scientific understanding of
      HNSCC reaches new levels, the field is poised to develop chemoprevention studies
      based on rigorous biological validation with accessibility to all affected
      individuals regardless of socioeconomic barriers.

PMID- 25868718
TI  - Stereotactic Radiosurgery in the Treatment of Recurrent CNS Lymphoma.
AB  - BACKGROUND: Central nervous system lymphoma (CNSL) is typically treated with
      chemotherapy and external beam radiation therapy (EBRT). Optimal management of
      recurrent CNSL is poorly defined. OBJECTIVE: We aim to determine the
      effectiveness of stereotactic radiosurgery in the treatment of recurrent CNSL.
      METHODS: We performed a retrospective analysis of patients having stereotactic
      radiosurgery (SRS) for recurrent intracranial CNSL between 1999 and 2011.
      RESULTS: Fourteen patients (20 tumors) underwent SRS. The median patient age was
      71 years (range, 18-82 years). Seven patients (50%) had primary CNSL. All had
      received prior chemotherapy, and nine patients (64%) had undergone prior whole
      brain radiotherapy (WBRT) with a median dose of 40 Gy in 25 fractions. The median
      preoperative Karnofsky Performance Score was 80. The median tumor volume was 6.7
      cm(3) (range, 0.5-37.7); the median margin dose was 15.5 Gy (range, 10-18).
      Eleven patients (79%) had tumor regression (n = 11) shown on MRI after SRS. The
      median overall survival after SRS was 9.5 months. No patient had a major
      radiation-related complication. CONCLUSION: Stereotactic radiosurgery for
      patients with recurrent CNSL is well tolerated and has a high rate of
      radiographic response. A marginal dose of 15.5 Gy or greater, a Karnofsky score
      of 80 or greater, and the absence of pre-SRS WBRT were associated with
      significantly longer overall survival. Stereotactic radiosurgery may be
      beneficial as an initial salvage therapy in the treatment of recurrent CNSL for
      properly selected patients.

PMID- 25868719
TI  - The Expanded Endoscopic Endonasal Approach to Petroclival Lesions: A Useful
      Adjunct to Traditional Skull Base Approaches.

PMID- 25868720
TI  - Toward a Better Understanding of Vasospasm and Delayed Cerebral Ischemia.

PMID- 25868722
TI  - Prism adaptation and unilateral neglect: Beyond an apparent negative result.

PMID- 25868721
TI  - Integrative network analysis reveals different pathophysiological mechanisms of
      insulin resistance among Caucasians and African Americans.
AB  - BACKGROUND: African Americans (AA) have more pronounced insulin resistance and
      higher insulin secretion than European Americans (Caucasians or CA) when matched
      for age, gender, and body mass index (BMI). We hypothesize that physiological
      differences (including insulin sensitivity [SI]) between CAs and AAs can be
      explained by co-regulated gene networks in tissues involved in glucose
      homeostasis. METHODS: We performed integrative gene network analyses of
      transcriptomic data in subcutaneous adipose tissue of 99 CA and 37 AA subjects
      metabolically characterized as non-diabetic, with a range of SI and BMI values.
      RESULTS: Transcripts negatively correlated with SI in only the CA or AA subjects
      were enriched for inflammatory response genes and integrin-signaling genes,
      respectively. A sub-network (module) with TYROBP as a hub enriched for genes
      involved in inflammatory response (corrected p = 1.7E-26) was negatively
      correlated with SI (r = -0.426, p = 4.95E-04) in CA subjects. SI was positively
      correlated with transcript modules enriched for mitochondrial metabolism in both
      groups. Several SI-associated co-expressed modules were enriched for genes
      differentially expressed between groups. Two modules involved in immune response
      to viral infections and function of adherens junction, are significantly
      correlated with SI only in CAs. Five modules involved in drug/intracellular
      transport and oxidoreductase activity, among other activities, are correlated
      with SI only in AAs. Furthermore, we identified driver genes of these race
      specific SI-associated modules. CONCLUSIONS: SI-associated transcriptional
      networks that were deranged predominantly in one ethnic group may explain the
      distinctive physiological features of glucose homeostasis among AA subjects.

PMID- 25868723
TI  - Indoor total volatile organic compounds exposure at 6 months followed by atopic
      dermatitis at 3 years in children.
AB  - BACKGROUND: Exposure to indoor air pollutants is thought to cause allergic
      inflammation. Volatile organic compounds (VOCs) are one of the aggravating
      factors of asthma and other allergic diseases. However, the influence of VOCs on
      development of atopic dermatitis is ambiguous in the clinical field. We therefore
      investigated the associations of indoor total volatile organic compounds (TVOCs)
      and development of atopic dermatitis in young Korean children. METHODS: From the
      birth cohort of a MOthers and Children's Environmental Health (MOCEH) study, 257
      infants, whose parents agreed with the environmental measurement, were enrolled.
      Total VOCs were measured in infant's bedrooms at the age of 6 month. A total of
      105 parents answered a questionnaire at 36 month. Concentrations of TVOCs were
      divided into two groups by third quartile (75th). Associations between the high
      VOCs exposure group and development of atopic dermatitis at the age of 36 months
      were estimated by multivariate logistic regression. RESULTS: The average
      concentration of TVOCs was 174.7 +/- 115.1 ?/m(3) . We defined the high TVOCs
      exposure group by those with more than 75 percentile of the distribution (242.1
      ?/m(3) ). An increased risk of atopic dermatitis was observed in the high TVOCs
      exposure group, after adjustment for parents history of allergy, household
      income, breast-feeding longer than 6 month (OR = 3.116, 95% Cl 1.041-9.323). Risk
      of atopic dermatitis was increased when the family bought new furniture within 1
      yr. CONCLUSION: Our results showed that exposure to high concentration of VOCs
      during infancy, an indoor pollutant, increased the risk of atopic dermatitis at
      36 months.

PMID- 25868724
TI  - Multiscale sensing of antibody-antigen interactions by organic transistors and
      single-molecule force spectroscopy.
AB  - Antibody-antigen (Ab-Ag) recognition is the primary event at the basis of many
      biosensing platforms. In label-free biosensors, these events occurring at solid
      liquid interfaces are complex and often difficult to control technologically
      across the smallest length scales down to the molecular scale. Here a molecular
      scale technique, such as single-molecule force spectroscopy, is performed across
      areas of a real electrode functionalized for the immunodetection of an
      inflammatory cytokine, viz. interleukin-4 (IL4). The statistical analysis of
      force-distance curves allows us to quantify the probability, the characteristic
      length scales, the adhesion energy, and the time scales of specific recognition.
      These results enable us to rationalize the response of an electrolyte-gated
      organic field-effect transistor (EGOFET) operated as an IL4 immunosensor. Two
      different strategies for the immobilization of IL4 antibodies on the Au gate
      electrode have been compared: antibodies are bound to (i) a smooth film of His
      tagged protein G (PG)/Au; (ii) a 6-aminohexanethiol (HSC6NH2) self-assembled
      monolayer on Au through glutaraldehyde. The most sensitive EGOFET (concentration
      minimum detection level down to 5 nM of IL4) is obtained with the first
      functionalization strategy. This result is correlated to the highest probability
      (30%) of specific binding events detected by force spectroscopy on Ab/PG/Au
      electrodes, compared to 10% probability on electrodes with the second
      functionalization. Specifically, this demonstrates that Ab/PG/Au yields the
      largest areal density of oriented antibodies available for recognition. More in
      general, this work shows that specific recognition events in multiscale
      biosensors can be assessed, quantified, and optimized by means of a nanoscale
      technique. 

PMID- 25868725
TI  - HGF-MET as a breast cancer biomarker.

PMID- 25868726
TI  - Malat1 regulates serum response factor through miR-133 as a competing endogenous
      RNA in myogenesis.
AB  - Metastasis-associated lung adenocarcinoma transcript 1 (Malat1) is an example of
      a functional long noncoding RNA involved in many biologic processes. However, the
      mechanisms for Malat1 in myogenesis are unclear. Serum response factor (SRF) is a
      pivotal transcription factor for muscle proliferation and differentiation and is
      reported to be a target gene for muscle-specific microRNA-133 (miR-133). In this
      study, we initially found that silencing Malat1 in the mouse myoblast C2C12 cell
      line inhibited myocyte differentiation and decreased Srf at both the RNA and
      protein levels. Srf silencing decreased Malat1 expression as well. Further study
      revealed that Malat1 contained an miR-133 functional target site, and the
      interplay between Malat1 and Srf was miR-133 dependent. We demonstrated that
      Malat1 modulates Srf through miR-133 as a competing endogenous RNA and
      established a novel connection among Malat1, miR-133, and Srf in myoblast
      differentiation.

PMID- 25868727
TI  - Vaccines targeting self-antigens: mechanisms and efficacy-determining parameters.
AB  - We recently showed that it is possible to compromise tumor vessel function and,
      as a consequence, suppress growth of aggressive preclinical tumors by immunizing
      against the tumor vascular markers extra domain-A (ED-A) or -B (ED-B) of
      fibronectin, using a fusion protein consisting of the ED-A or ED-B peptide fused
      to bacterial thioredoxin. To address the mechanism behind fusion protein-induced
      immunization and the specific contribution of the different vaccine constituents
      to elicit an anti-self-antibody response, we immunized mice with modified or
      unmodified self-antigens, combined with different adjuvant components, and
      analyzed antibody responses by ELISA in sera. Several essential requirements to
      circumvent tolerance were identified: (1) a potent pattern recognition receptor
      agonist like an oligonucleotide containing unmethylated cytosine and guanine
      dinucleotides (CpG); (2) a depot adjuvant to keep the CpG at the site of
      injection; and (3) the presence of foreign sequences in the vaccine protein. Lack
      of either of these factors abolished the anti-self-response (P = 0.008). In mice
      genetically deficient for type I IFN signaling, there was a 60% reduction in the
      anti-self-response compared with wild-type (P = 0.011), demonstrating a key role
      of this pathway in CpG-induced circumvention of self-tolerance. Identification of
      these mechanistic requirements to generate a potent anti-self-immune response
      should significantly aid the design of efficient, specific, and safe therapeutic
      cancer vaccines.

PMID- 25868728
TI  - A heteromeric potassium channel involved in the modulation of the plasma membrane
      potential is essential for the survival of African trypanosomes.
AB  - Discovery of novel drug targets may lead to improved treatment of
      trypanosomiasis. We characterize here 2 gene products of Trypanosoma brucei that
      are essential for the growth of bloodstream form (BSF) parasites, as shown by RNA
      interference (RNAi)-mediated down-regulation of the individual mRNAs. The primary
      sequences of the 2 proteins--protein encoded by gene Tb927.1.4450 (TbK1) and
      protein encoded by gene Tb927.9.4820 (TbK2)--indicate that both belong to the
      family of putative, Ca(2+)-activated potassium channels. The proteins were
      expressed in Xenopus laevis oocytes and their functions investigated by use of
      electrophysiological techniques. Only combined expression of TbK1 and TbK2
      results in the formation of sizeable currents, indicating that these proteins
      probably assemble into a heteromeric ion channel. The current mediated by this
      channel shows little time and voltage dependence and displays a permeability
      ratio of K(+)/Na(+) of >20. The known potassium channel blocker barium inhibits
      this channel with a half-maximal inhibitory concentration (IC50) of 98 +/- 15
      MUM. The membrane potential of trypanosomes was measured with a fluorescent dye.
      Individual RNAi-mediated down-regulation of TbK1 or TbK2 eliminates a potassium
      conductance in the plasma membrane of BSF. Thus, this heteromeric potassium
      channel is involved in the modulation of the plasma membrane potential and
      represents a novel drug target in T. brucei.

PMID- 25868730
TI  - D-Aspartate: An endogenous NMDA receptor agonist enriched in the developing brain
      with potential involvement in schizophrenia.
AB  - Free D-aspartate and D-serine occur at substantial levels in the mammalian brain.
      D-Serine is a physiological endogenous co-agonist for synaptic N-Methyl D
      Aspartate (NMDA) receptors (NMDARs), and is involved in the pathophysiology of
      schizophrenia. Much less is known about the biological meaning of D-aspartate. D
      Aspartate is present at high levels in the embryo brain and strongly decreases at
      post-natal phases. Temporal reduction of D-aspartate levels depends on the post
      natal onset of D-aspartate oxidase (DDO), an enzyme able to selectively
      catabolize this D-amino acid. Pharmacological evidence indicates that D-aspartate
      binds to and activates NMDARs. Characterization of genetic and pharmacological
      mouse models with abnormally higher levels of D-aspartate has evidenced that
      increased D-aspartate enhances hippocampal NMDAR-dependent synaptic plasticity,
      dendritic morphology and spatial memory. In line with the hypothesis of a
      hypofunction of NMDARs in the pathogenesis of schizophrenia, it has been shown
      that increased D-aspartate levels also improve brain connectivity, produce
      corticostriatal adaptations resembling those observed after chronic haloperidol
      treatment, and protects against prepulse inhibition deficits and abnormal
      circuits activation induced by psychotomimetic drugs. In healthy humans, genetic
      variation predicting reduced expression of DDO in post-mortem prefrontal cortex
      is associated with greater prefrontal gray matter and activity during working
      memory. On the other side, evaluation of D-aspartate content in post-mortem
      patients with schizophrenia has shown a significant reduction of this D-amino
      acid in the prefrontal cortex and striatum. Generation of mouse models with
      reduced embryonic levels of D-aspartate may disclose unprecedented role for D
      aspartate in developmental brain processes associated with vulnerability to
      psychotic-like symptoms.

PMID- 25868729
TI  - A common sugar-nucleotide-mediated mechanism of inhibition of (glycosamino)glycan
      biosynthesis, as evidenced by 6F-GalNAc (Ac3).
AB  - Glycosaminoglycan (GAG) polysaccharides have been implicated in a variety of
      cellular processes, and alterations in their amount and structure have been
      associated with diseases such as cancer. In this study, we probed 11 sugar
      analogs for their capacity to interfere with GAG biosynthesis. One analog, with a
      modification not directly involved in the glycosidic bond formation, 6F-N-acetyl
      d-galactosamine (GalNAc) (Ac3), was selected for further study on its metabolic
      and biologic effect. Treatment of human ovarian carcinoma cells with 50 MUM 6F
      GalNAc (Ac3) inhibited biosynthesis of GAGs (chondroitin/dermatan sulfate by ~50
      60%, heparan sulfate by ~35%), N-acetyl-d-glucosamine (GlcNAc)/GalNAc containing
      glycans recognized by the lectins Datura stramonium and peanut agglutinin (by ~74
      and ~43%, respectively), and O-GlcNAc protein modification. With respect to
      function, 6F-GalNAc (Ac3) treatment inhibited growth factor signaling and reduced
      in vivo angiogenesis by ~33%. Although the analog was readily transformed in
      cells into the uridine 5'-diphosphate (UDP)-activated form, it was not
      incorporated into GAGs. Rather, it strongly reduced cellular UDP-GalNAc and UDP
      GlcNAc pools. Together with data from the literature, these findings indicate
      that nucleotide sugar depletion without incorporation is a common mechanism of
      sugar analogs for inhibiting GAG/glycan biosynthesis.

PMID- 25868731
TI  - Ultrasonographic differentiation of bezoar from feces in small bowel obstruction.
AB  - PURPOSE: To evaluate ultrasonographic accuracy in the differentiation of a bezoar
      from feces in a small bowel obstruction showing feces-like material just proximal
      to the transitional zone in abdominal computed tomography (CT). METHODS: This
      study included 14 patients who showed feces-like material just proximal to the
      transitional zone, among 302 patients diagnosed with small bowel obstruction on
      abdominal CT. The diagnostic signs of a bezoar on ultrasonography included an arc
      like surfaced intraluminal mass, posterior acoustic shadow and twinkling
      artifacts. The diagnostic performance of ultrasonography in each patient was
      compared with a final diagnosis that was surgically or clinically made. RESULTS:
      Among the 14 patients, seven were ultrasonographically diagnosed as having a
      bezoar, and five of the seven were surgically diagnosed as having a phytobezoar.
      The remaining two of the seven showed complete symptomatic improvement before
      surgery. The other seven patients were ultrasonographically diagnosed as not
      having a bezoar. Among them, six patients were conservatively treated with
      symptomatic improvement, suggesting the absence of a bezoar. The remaining one
      patient was confirmed not to have a bezoar during adhesiolysis. In all patients,
      the ultrasonographic diagnosis agreed with the clinically confirmed diagnosis.
      CONCLUSION: Ultrasonography might be an accurate method for the differential
      diagnosis of feces-like material just proximal to the transitional zone in
      abdominal CT. It can help radiologists to quickly and easily diagnose a bezoar.

PMID- 25868732
TI  - Contrast-enhanced ultrasonography of the carotids.
AB  - Contrast-enhanced ultrasonography of the carotids has recently emerged as a
      complementary examination to conventional carotid Doppler ultrasonography. It is
      an examination providing improved visualization of the vascular lumen, more
      accurate and detailed delineation of the vascular wall, and identification of
      atherosclerotic plaques. Moreover, contrast-enhanced ultrasonography has specific
      advantages over conventional ultrasonography and plays an important role in the
      diagnosis of the vulnerable carotid plaque, as it can identify intraplaque
      neovascularization and carotid plaque ulceration. Given the specific advantages
      and improved imaging of the carotids provided by this method, radiologists should
      be familiar with it. This pictorial essay illustrates the advantages of this
      technique and discusses its value in the imaging of carotid arteries. 

PMID- 25868733
TI  - Ultrasonography of soft tissue "oops lesions".
AB  - In this article, I would like to define "oops lesions" as soft tissue mass-like
      lesions that involve surprise or embarrassment for radiologists following the
      final diagnosis. Examples of "oops lesions" include malignant tumors that appear
      benign, malignancy-mimicking benign tumors, incorrect identification of epidermal
      inclusion cysts, and soft tissue pseudotumors. Ultrasonography (US) findings are
      very helpful in the diagnosis of soft tissue tumors; however, the diagnosis of
      soft tissue tumors on the basis of US findings alone has some limitations.
      Therefore, clinical findings, laboratory data, findings from additional imaging
      modalities, and demographic data of patients should be considered together with
      US findings. 

PMID- 25868734
TI  - Editorial Comment.

PMID- 25868735
TI  - Critical Analysis of Patient-reported Complaints and Complications After
      Urethroplasty for Bulbar Urethral Stricture Disease.
AB  - OBJECTIVE: To evaluate the full spectrum of postoperative complications and
      patient-reported complaints after urethroplasty for bulbar urethral stricture
      disease. MATERIALS AND METHODS: We performed a retrospective review of our
      institutional database for all patients who underwent urethroplasty from January
      1, 2002 to December 1, 2012. We recorded all postoperative complications and
      patient-reported complaints and grouped them by the Clavien-Dindo classification
      of surgical complications and into the following categories: perioperative,
      infectious, anatomic, sexual dysfunction, and voiding related. The Fisher exact
      test was used to calculate statistical differences among repair types and
      etiology. RESULTS: Three hundred twenty-five men underwent urethroplasty by 2
      surgeons (G.D.W. and A.C.P.) during the period reviewed. Two hundred ninety-two
      of 325 men (90%) had sufficient follow-up data available. One hundred eleven of
      292 men (38%) reported a total of 146 postoperative complications or complaints.
      Forty-seven of 111 men (42%) were classified as having a perioperative
      complication, 17 of 111 (15.3%) as infectious, 8 of 111 (7.2%) as anatomic, 29 of
      111 (26.1%) as sexual dysfunction, and 32 of 111 (28.8%) as voiding related. The
      majority of complications were classified as Clavien grade I (87 of 146, 60%).
      Forty-seven of 146 men (32%) were classified as having Clavien grade II, 9 of 146
      (6%) as grade III, and 3 of 146 (2%) as grade IV. There were no grade V
      complications. Patients with iatrogenic etiology had a higher rate of infectious
      related complications when compared with idiopathic or traumatic (17.5% vs 3.7%,
      4.8%, respectively; P = .008). CONCLUSION: Urethroplasty continues to have
      excellent outcomes with acceptable complication rates, the majority of which are
      self-reported complaints about voiding, scrotal and/or perineal neuralgia, and
      sexual dysfunction and appear to have minimal long-term sequelae.

PMID- 25868736
TI  - Assessing the Impact of Barbed Suture on Vesicourethral Anastomosis During
      Minimally Invasive Radical Prostatectomy: A Systematic Review and Meta-analysis.
AB  - OBJECTIVE: To examine the effectiveness of barbed suture (BS) compared with
      conventional sutures for vesicourethral anastomosis (VUA) during minimally
      invasive radical prostatectomy (RP). METHODS: Relevant studies comparing the
      safety and efficacy of BS with conventional sutures during minimally invasive RP
      were identified through a literature search using MEDLINE, EMBASE, and the
      Cochrane Library. The outcome measures included baseline characteristics, primary
      outcomes, and secondary outcomes. RESULTS: Ten studies (378 cases and 369
      controls) were included. No significant differences between the 2 groups were
      detected in any of the baseline variables except for age (P = .02). The BS group
      had a shorter operation time (mean difference [MD], 10.54; 95% confidence
      interval [CI], -14.38 to -6.69; P <.01), a shorter VUA time (MD, -5.35; 95% CI, 
      7.44 to -3.25; P <.01), and a shorter posterior reconstruction time (MD, -0.56;
      95% CI, -1.10 to -0.02; P = .04) than those in the conventional sutures group. No
      significant differences were detected between the 2 groups in other outcomes of
      interest. In subgroup and sensitivity analyses, there was no change in the
      significance of any of the outcomes. CONCLUSION: This meta-analysis indicates
      that VUA using BS as opposed to conventional suture is associated with a shorter
      operative time, comparable postoperative complication rate, and convenience for
      manipulation, which is of benefit to the surgeon learning robot-assisted RP and
      laparoscopic RP. Given that the inherent limitations, future well-designed
      randomized controlled trials are required to confirm our findings.

PMID- 25868737
TI  - Comparison between Open Epididymal Cystectomy and Minimal Resection of Epididymal
      Cysts Using a Scrotoscope: A Clinical Trial for the Evaluation of a New Surgical
      Technique.
AB  - OBJECTIVE: To provide a new surgical technique for epididymal cyst (EC) treatment
      and to assess its safety and efficiency. METHODS: Forty-eight patients with
      symptomatic EC were randomized into 2 groups. One group (n = 23) received
      traditional open epididymal cystectomy (OEC) and the other group (n = 25)
      underwent minimal epididymal cystectomy with scrotoscope (MECS), which provided a
      clear vision of scrotal contents. Demographic information and perioperative and
      postoperative outcomes data were obtained and analyzed during a 2- to 6-month
      follow-up. RESULTS: No significant differences between the OEC and MECS groups
      were found in demographic information. Compared with OEC group, the MECS group
      had a shorter operating time (18.6 +/- 2.9 vs 54.5 +/- 7.0 minutes; P <.05),
      shorter incision length (1.1 +/- 0.2 vs 4.8 +/- 0.6 cm; P <.05), and less blood
      loss (4.6 +/- 1.6 vs 17.0 +/- 3.1 g; P <.05). Except for the 8.0% rate (2 of 25)
      of scrotal edema after MECS and 17.4% rate (4 of 23) of scrotal hematoma after
      OEC, both groups resulted in 0% incidence of testis or epididymis injury, wound
      infection, and cyst recurrence based on postoperative outcome data. Significant
      differences were observed after MECS compared with those after OEC based on the
      rates of symptom relief (95.2% vs 61.1%; P <.05) and days of wound pain (12.1 +/-
      2.6 vs 17.7 +/- 4.1 days; P <.05). CONCLUSION: For the first time, our study
      applied scrotoscope as a new alternative technique for EC treatment. Scrotoscope
      provides a clear field of vision and makes tissues harvested available for
      pathologic examination when performing decortications of EC. The results suggest
      MECS may be a safe, effective, and encouraging new technique.

PMID- 25868738
TI  - A Multi-institutional Evaluation of the Management and Outcomes of Long-segment
      Urethral Strictures.
AB  - OBJECTIVE: To evaluate the treatment options and surgical outcomes of long
      segment urethral strictures-a review of the largest, international, multi
      institutional series. METHODS: A retrospective review was performed of patients
      treated with strictures >=8 cm at 8 international centers. Endpoints analyzed
      included surgical complications and recurrence. RESULTS: Four hundred sixty-six
      patients were identified. Treatment intervals ranged from December 27, 1984 to
      November 9, 2013. Dorsal onlay buccal mucosal graft (BMG) was the most common
      procedure (223, 47.9%); others included first- and second-stage Johanson
      urethroplasty (162 [34.8%] and 56 [12%], respectively), fasciocutaneous (FC)
      flaps (8, 1.7%), and a combination flap and graft (17, 3.6%). Overall success was
      achieved in 361 patients (77.5%) with a mean follow-up of 20 months. Second-stage
      Johanson urethroplasty was found to have a higher recurrence rate compared with
      that of 1-stage BMG urethroplasty (35.7% vs 17.5%, respectively; P <.01). This
      was also true in cases of lichen sclerosus (14.0% vs 47.8%, respectively; P
      <.01). Otherwise, success rates were similar. Urethroplasties performed with FC
      flaps had a higher complication rate compared with those without (32% vs 14%,
      respectively; P = .02). Prior dilation or urethrotomy, higher number of prior
      dilations or urethrotomies, abnormal voiding cystourethrogram, and skin grafts
      all portend a higher recurrence rate. On logistic regression analysis, only
      second-stage Johanson had an increased odds ratio of recurrence compared with
      that of BMG (2.82 [1.41-5.86]). CONCLUSION: Long-segment strictures can be
      treated with high success rates in experienced hands. BMG was more successful
      than second-stage Johanson urethroplasty. FC flaps, although successful, had high
      complication rates.

PMID- 25868739
TI  - Blood SC5b-9 complement levels increase at parturition during term and preterm
      labor.
AB  - We explored the hypothesis that complement, an innate and adaptive immune
      effector, is active in the plasma of parturient women and is deposited on fetal
      membranes collected after delivery. A cross-sectional study was designed to
      evaluate complement activity at parturition. Pregnant women (n = 97) between 15
      and 41 years of age were enrolled in a hospital protocol during the perinatal
      period to assess both SC5b-9 complement activity in blood and complement
      deposition on fetal membranes during parturition. Soluble SC5b-9 complement
      activity in plasma fractions was measured using a standard enzyme-linked
      immunosorbent assay (ELISA) that included specific anti-complement antibodies.
      Complement deposition on membranes was analyzed using immuno-dot blots and
      immunohistochemistry. Soluble SC5b-9 complement complex levels were increased in
      the plasma of women during term labor (TL; median 3361; range 1726-5670 ng/mL),
      preterm labor (PL; median 2958; range 1552-7092 ng/mL), and preterm premature
      rupture of membranes (PPROM; median 2272; range 167-6540 ng/mL) compared with
      pregnant women who were not in labor (P; median 1384; range 174-4570 ng/mL; P <
      0.001, Kruskal-Wallis test). Active complement, as assessed by the C9 neo-antigen
      in C5b-9 complexes, was deposited on fetal membranes, with no difference between
      term and preterm delivery. The deposition of active complement on fetal membranes
      was confirmed by immunohistochemistry. Women who underwent non-labor-indicated
      Cesarean sections did not exhibit complement deposition. Soluble SC5b-9
      complement complex levels increased in the plasma of women during parturition,
      and complement C5b-9 complexes were deposited on fetal membranes.

PMID- 25868740
TI  - Comparing interval and continuous exercise training regimens on neurotrophic
      factors in rat brain.
AB  - The research literature suggests that oxidative stress and pro-inflammatory
      factors influence neurotrophins in vitro. However, there is insufficient
      information about their effects on exercise training conditions, especially
      during high intensity trainings. This study aimed to compare the effects of
      6weeks of high intensity interval and continuous training regimens on brain
      derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor
      (GDNF), hydrogen peroxide (H2O2), and tumor necrosis factor alpha (TNF-alpha) in
      the rat brain. For this purpose, twenty-four Albino Wistar rats were divided into
      sedentary control (SC), high intensity interval training (HIIT), and continuous
      training (CT) groups. Both HIIT and CT regimens increased H2O2 level and TNF
      alpha concentration in the brain, and the alterations made were greater following
      HIIT than CT. In addition, both HIIT and CT regimens increased BDNF and GDNF
      concentrations significantly, with a higher elevation following HIIT than CT.
      Furthermore, H2O2 level and TNF-alpha concentration correlated positively with
      both BDNF and GDNF concentrations. Generally, high intensity interval training
      regimen, rather than continuous training regimen, is highly potential to improve
      BDNF and GDNF through a greater increase in H2O2 and TNF-alpha as oxidative
      stress and pro-inflammatory factors. 

PMID- 25868741
TI  - Pressure-controlled intermittent coronary sinus occlusion (PICSO) in acute ST
      segment elevation myocardial infarction: results of the Prepare RAMSES safety and
      feasibility study.
AB  - AIMS: Pressure-controlled intermittent coronary sinus occlusion (PICSO) may
      improve myocardial perfusion after pPCI. We evaluated the safety and feasibility
      of PICSO after pPCI for STEMI, and explored its effects on infarct size and
      myocardial function. METHODS AND RESULTS: Thirty patients were enrolled following
      successful pPCI of a left anterior descending coronary artery culprit lesion for
      anterior STEMI, in whom PICSO for 90 minutes was attempted. Infarct size and
      myocardial function were assessed by cardiovascular magnetic resonance (CMR) at
      two to five days and four months post pPCI. An independent core laboratory
      selected matched historical control patients with CMR data for comparison. PICSO
      was initiated in 19 patients (63%), and could be maintained for 90 (+/-2) minutes
      in 12 patients (40%). Major adverse safety events occurred in one patient (3%).
      Comparing all PICSO-treated patients to matched controls demonstrated no
      significant differences in infarct size or myocardial recovery. However, infarct
      size reduction from two to five days to four months was greater for patients
      successfully treated with PICSO compared with matched controls (41.6+/-8.2% vs.
      27.7+/-9.9%, respectively; p=0.04). CONCLUSIONS: PICSO is safe in the setting of
      STEMI, although feasibility was limited. Administration of sufficient PICSO
      therapy may be associated with enhanced myocardial recovery during follow-up,
      warranting further evaluation of this novel therapy.

PMID- 25868742
TI  - Procedural outcomes of patients with calcified lesions treated with bioresorbable
      vascular scaffolds.
AB  - AIMS: To compare the feasibility, procedural and clinical outcomes after
      implantation of bioresorbable vascular scaffolds (BVS) in patients with calcified
      lesions. METHODS AND RESULTS: We assessed the feasibility of BVS implantation and
      procedural outcomes in patients with and without calcific lesions. The primary
      outcome was angiographic and procedural success. Secondary outcomes included
      major adverse cardiovascular events (MACE). Of 163 patients, 62 (38%) had
      calcified lesions. Patients with calcific lesions had a higher prevalence of
      diabetes (35.5% vs. 22.8%, p=0.078) and chronic kidney disease (31.1% vs. 13.9%,
      p=0.008), and higher SYNTAX scores (18.9+/-9.7 vs. 15.1+/-9.0, p=0.017). Calcific
      lesions required longer procedures (126.4+/-39.8 vs. 106.9+/-37.1 min, p=0.015),
      more frequent use of dedicated devices and IVUS. Acute gain (1.83+/-0.6 vs.
      1.86+/-0.6, p=0.732) and angiographic success were similar (98% non-calcific vs.
      95.2% calcific, p=0.369), whereas procedural success was reduced in patients with
      calcific lesions (94.1% vs. 83.9%, p=0.034) due to higher rates of periprocedural
      myocardial infarction (MI) (5% vs. 13.1%, p=0.067). During the median follow-up
      time of 14 months MACE rates (10.9% non-calcific vs. 12.9% calcific, plog
      rank=0.546) were similar. CONCLUSIONS: Treating calcific lesions with BVS is
      feasible with high angiographic success rates, at the expense of longer procedure
      times, aggressive lesion preparation and increased rates of periprocedural MI.

PMID- 25868743
TI  - Design, synthesis and biological evaluation of new hybrid anticonvulsants derived
      from N-benzyl-2-(2,5-dioxopyrrolidin-1-yl)propanamide and 2-(2,5-dioxopyrrolidin
      1-yl)butanamide derivatives.
AB  - The purpose of this study was to synthesize the library of 33 new N-benzyl-2-(2,5
      dioxopyrrolidin-1-yl)propanamides, 2-(3-methyl-2,5-dioxopyrrolidin-1
      yl)propanamides, and 2-(2,5-dioxopyrrolidin-1-yl)butanamides as potential new
      hybrid anticonvulsant agents. These hybrid molecules join the chemical fragments
      of well-known antiepileptic drugs (AEDs) such as ethosuximide, levetiracetam, and
      lacosamide. The coupling reaction of the 2-(2,5-dioxopyrrolidin-1-yl)propanoic
      acid, 2-(3-methyl-2,5-dioxopyrrolidin-1-yl)propanoic acid, or 2-(2,5
      dioxopyrrolidin-1-yl)butanoic acid with the appropriately substituted
      benzylamines in the presence of the coupling reagent, N,N-carbonyldiimidazole
      (CDI) generated the final compounds 4-36. Spectral data acquired via (1)H NMR,
      (13)C NMR, and LC-MS confirmed the chemical structures of the newly prepared
      compounds. The initial anticonvulsant screening was performed in mice
      intraperitoneally (ip), using the maximal electroshock seizure (MES) and
      subcutaneous pentylenetetrazole (scPTZ) seizure tests. The rotarod test
      determined the acute neurological toxicity (NT). The results of preliminary
      pharmacological screening revealed that 25 compounds showed protection in half or
      more of the animals tested in the MES and/or scPTZ seizure models at the fixed
      dose of 100mg/kg. The broad spectra of activity across the preclinical seizure
      models displayed compounds 4, 7, 8, 13, 15-18, 24, and 26. The quantitative
      pharmacological studies in mice demonstrated the highest protection for compounds
      4 (ED50 MES=67.65 mg/kg, ED50scPTZ=42.83 mg/kg); 8 (ED50 MES=54.90 mg/kg,
      ED50scPTZ=50.29 mg/kg); and 20 (ED50scPTZ=47.39 mg/kg). These compounds were
      distinctly more potent and provided better safety profiles in the rotarod test
      compared to valproic acid or ethosuximide, which were used as model AEDs.
      Compound 8 underwent only a slight metabolic change by the human liver microsomes
      (HLMs), and also did not affect the activity of human cytochrome P450 isoform,
      CYP3A4, in the in vitro assays.

PMID- 25868744
TI  - Synthesis of new N-benzylpiperidine derivatives as cholinesterase inhibitors with
      beta-amyloid anti-aggregation properties and beneficial effects on memory in
      vivo.
AB  - Due to the complex nature of Alzheimer's disease, multi-target-directed ligand
      approaches are one of the most promising strategies in the search for effective
      treatments. Acetylcholinesterase, butyrylcholinesterase and beta-amyloid are the
      predominant biological targets in the search for new anti-Alzheimer's agents. Our
      aim was to combine both anticholinesterase and beta-amyloid anti-aggregation
      activities in one molecule, and to determine the therapeutic potential in vivo.
      We designed and synthesized 28 new compounds as derivatives of donepezil that
      contain the N-benzylpiperidine moiety combined with the phthalimide or indole
      moieties. Most of these test compounds showed micromolar activities against
      cholinesterases and aggregation of beta-amyloid, combined with positive results
      in blood-brain barrier permeability assays. The most promising compound 23 (2-(8
      (1-(3-chlorobenzyl)piperidin-4-ylamino)octyl)isoindoline-1,3-dione) is an
      inhibitor of butyrylcholinesterase (IC50=0.72 MUM) that has beta-amyloid anti
      aggregation activity (72.5% inhibition at 10 MUM) and can cross the blood-brain
      barrier. Moreover, in an animal model of memory impairment induced by
      scopolamine, the activity of 23 was comparable to that of donepezil. The selected
      compound 23 is an excellent lead structure in the further search for new anti
      Alzheimer's agents.

PMID- 25868745
TI  - Novel thiazolo[3,2-b]-1,2,4-triazoles derived from naproxen with analgesic/anti
      inflammatory properties: Synthesis, biological evaluation and molecular modeling
      studies.
AB  - 3-Substituted-1,2,4-triazole-5-thiones are versatile synthetic intermediates for
      the preparation of several biologically active N-bridged heterocyclic compounds,
      given that they have two reactive sites, thiocarbonyl and an amine nitrogen
      (N1/N4). For several years, our interest has focused on the synthesis of novel
      heterocyclic systems derived from 3-substituted-1,2,4-triazole-5-thiones having
      analgesic/anti-inflammatory activity. In this study, a series of novel
      thiazolo[3,2-b]-1,2,4-triazole-6(5H)-one derivatives bearing naproxen was
      synthesized and evaluated for their in vivo analgesic and anti-inflammatory
      properties in acute experimental pain and inflammation models. The compounds were
      also tested for their ulcerogenic potential. Our findings showed that all the
      newly synthesized derivatives attenuate nociception and inflammation compared
      with a control. All the synthesized compounds exhibited much lower ulcerogenic
      risk than the standard drugs indomethacin and naproxen. Some compounds with
      significant analgesic and/or anti-inflammatory activities as well as low ulcer
      scores were further evaluated for in vitro COX-1 and COX-2 inhibitory potential
      in a COX-catalyzed prostaglandin biosynthesis assay. Among the tested compounds,
      compound 1q showed the highest selectivity index (SI) of 4.87. The binding mode
      for some of the tested compounds to the cyclooxygenase (COX) enzymes was
      predicted using docking studies. 

PMID- 25868747
TI  - Understanding allosteric interactions in G protein-coupled receptors using
      Supervised Molecular Dynamics: A prototype study analysing the human A3 adenosine
      receptor positive allosteric modulator LUF6000.
AB  - The search for G protein-coupled receptors (GPCRs) allosteric modulators
      represents an active research field in medicinal chemistry. Allosteric modulators
      usually exert their activity only in the presence of the orthosteric ligand by
      binding to protein sites topographically different from the orthosteric cleft.
      They therefore offer potentially therapeutic advantages by selectively
      influencing tissue responses only when the endogenous agonist is present. The
      prediction of putative allosteric site location, however, is a challenging task.
      In facts, they are usually located in regions showing more structural variation
      among the family members. In the present work, we applied the recently developed
      Supervised Molecular Dynamics (SuMD) methodology to interpret at the molecular
      level the positive allosteric modulation mediated by LUF6000 toward the human
      adenosine A3 receptor (hA3 AR). Our data suggest at least two possible mechanisms
      to explain the experimental data available. This study represent, to the best of
      our knowledge, the first case reported of an allosteric recognition mechanism
      depicted by means of molecular dynamics simulations. 

PMID- 25868746
TI  - Discovery of novel spiro 1,3,4-thiadiazolines as potent, orally bioavailable and
      brain penetrant KSP inhibitors.
AB  - Kinesin spindle protein (KSP) is a mitotic kinesin that is expressed only in
      proliferating cells and plays a key role in spindle pole separation, formation of
      a bipolar mitotic spindle, as well as centrosome separation and maturation.
      Inhibition of KSP has the potential to provide anti-tumor activity while avoiding
      peripheral neuropathy associated with some microtubule-targeted drugs. Based on
      MK-0731 and related heterocyclic compounds targeting the KSP monastrol binding
      site, structurally constrained spiro-cyclic KSP inhibitors were designed. In
      particular, rapid evaluation and optimization of the novel spiro 1,3,4
      thiadiazolines resulted in a series of potent KSP inhibitors demonstrating
      mechanism based activities in cells, including induction of the mitotic marker
      phospho-histone H3 and induction of monaster spindle formation. Further
      optimization of the pharmacokinetic (PK) properties afforded MK-8267 as a potent,
      orally bioavailable and brain penetrant KSP inhibitor which showed anti-tumor
      activity in preclinical xenograft models. 

PMID- 25868748
TI  - Anti-parallel triplexes: Synthesis of 8-aza-7-deazaadenine nucleosides with a 3
      aminopropynyl side-chain and its corresponding LNA analog.
AB  - The phosphoramidites of DNA monomers of 7-(3-aminopropyn-1-yl)-8-aza-7
      deazaadenine (Y) and 7-(3-aminopropyn-1-yl)-8-aza-7-deazaadenine LNA (Z) are
      synthesized, and the thermal stability at pH 7.2 and 8.2 of anti-parallel
      triplexes modified with these two monomers is determined. When, the anti-parallel
      TFO strand was modified with Y with one or two insertions at the end of the TFO
      strand, the thermal stability was increased 1.2 degrees C and 3 degrees C at pH
      7.2, respectively, whereas one insertion in the middle of the TFO strand
      decreased the thermal stability 1.4 degrees C compared to the wild type
      oligonucleotide. In order to be sure that the 3-aminopropyn-1-yl chain was
      contributing to the stability of the triplex, the nucleobase X without the
      aminopropynyl group was inserted in the same positions. In all cases the thermal
      stability was lower than the corresponding oligonucleotides carrying the 3
      aminopropyn-1-yl chain, especially at the end of the TFO strand. On the other
      hand, the thermal stability of the anti-parallel triplex was dramatically
      decreased when the TFO strand was modified with the LNA monomer analog Z in the
      middle of the TFO strand (DeltaTm=-9.1 degrees C). Also the thermal stability
      decreased about 6.1 degrees C when the TFO strand was modified with Z and the
      Watson-Crick strand with adenine-LNA (A(L)). The molecular modeling results
      showed that, in case of nucleobases Y and Z a hydrogen bond (1.69 and 1.72A,
      respectively) was formed between the protonated 3-aminopropyn-1-yl chain and one
      of the phosphate groups in Watson-Crick strand. Also, it was shown that the
      nucleobase Y made a good stacking and binding with the other nucleobases in the
      TFO and Watson-Crick duplex, respectively. In contrast, the nucleobase Z with LNA
      moiety was forced to twist out of plane of Watson-Crick base pair which is
      weakening the stacking interactions with the TFO nucleobases and the binding with
      the duplex part.

PMID- 25868749
TI  - Molecular modeling of the human P2Y14 receptor: A template for structure-based
      design of selective agonist ligands.
AB  - The P2Y14 receptor (P2Y14R) is a Gi protein-coupled receptor that is activated by
      uracil nucleotides UDP and UDP-glucose. The P2Y14R structure has yet to be solved
      through X-ray crystallography, but the recent agonist-bound crystal structure of
      the P2Y12R provides a potentially suitable template for its homology modeling for
      rational structure-based design of selective and high-affinity ligands. In this
      study, we applied ligand docking and molecular dynamics refinement to a P2Y14R
      homology model to qualitatively explain structure-activity relationships of
      previously published synthetic nucleotide analogues and to probe the quality of
      P2Y14R homology modeling as a template for structure-based design. The P2Y14R
      model supports the hypothesis of a conserved binding mode of nucleotides in the
      three P2Y12-like receptors involving functionally conserved residues. We predict
      phosphate group interactions with R253(6.55), K277(7.35), Y256(6.58) and
      Q260(6.62), nucleobase (anti-conformation) pi-pi stacking with Y102(3.33) and the
      role of F191(5.42) as a means for selectivity among P2Y12-like receptors. The
      glucose moiety of UDP-glucose docked in a secondary subpocket at the P2Y14R
      homology model. Thus, P2Y14R homology modeling may allow detailed prediction of
      interactions to facilitate the design of high affinity, selective agonists as
      pharmacological tools to study the P2Y14R. 

PMID- 25868751
TI  - [New technologies in diabetology. How far are we from a closed loop?].
AB  - Today, assistive technologies are highly important in the treatment of diabetes,
      especially in the therapy of type 1 diabetes. The use of insulin pumps, for
      example, has become an established form of treatment. Modern insulin pumps offer
      various functions, such as different basal rate profiles, split delivery of the
      meal bolus, and integrated bolus calculators. Some pumps are additionally
      connected to a blood glucose meter or a continuous glucose-monitoring sensor.
      Several minimally invasive needle-type sensor systems for continuous tissue
      glucose monitoring are already available. Recent developments aim at increasing
      the functionality of insulin pumps and the improvements of sensors for continuous
      glucose monitoring. In addition, many research groups are working on closing the
      loop between these two components and thus developing an artificial pancreas,
      which automatically regulates insulin delivery. The first steps have already been
      taken and bolus calculators or sensor-augmented insulin pumps with suspension of
      insulin delivery are now available. Many experimental models show promising
      results. Prior to the implementation of a fully automated system for everyday
      use, however, partially automated systems that require user input are to be
      expected. This article aims at giving an overview of the current state of
      development in the field of diabetes technology. 

PMID- 25868752
TI  - Relationship of vitamin D status with lung function and exercise capacity in
      COPD.
AB  - BACKGROUND AND OBJECTIVE: The relationship between blood vitamin D level and
      clinical parameters in patients with chronic obstructive pulmonary disease (COPD)
      has been reported with conflicting results. We explored the effects of vitamin D
      on clinical characteristics of patients with COPD in Korea. METHODS: The study
      population comprised 193 patients with COPD from Korean Obstructive Lung Disease
      Cohort. The plasma level of 25-OH vitamin D3 (25-OH-VitD3) was measured every
      year along with various clinical parameters such as lung function, 6-min walking
      (6MW) distance, quality of life, exacerbations and emphysema index. Generalized
      estimating equations and linear mixed model were used for statistical analysis.
      RESULTS: Of the 193 patients, 12 (6.2%), 28 (14.5%) and 153 (79.3%) were
      categorized into normal, insufficiency and deficiency groups. Clustered analysis
      showed that the plasma 25-OH-VitD3 level was associated with the post
      bronchodilator ratio of force expiratory volume in 1 s/forced vital capacity
      (FEV1 /FVC) (estimated = 0.001; P = 0.022). The vitamin D deficiency group showed
      lower FEV1 (estimated = -0.129, P = 0.043), FEV1 % predicted (estimated = -4.994,
      P = 0.029) and FEV1 /FVC ratio (estimated = -0.048, P = 0.001) than did the non
      deficiency group. The 6MW distance tended to be shorter in deficiency group
      (estimated = -17.26, P = 0.069) than in non-deficiency group. Quality of life,
      exacerbation and emphysema index were not associated with plasma 25-OH-VitD3
      level. CONCLUSIONS: We demonstrated a high prevalence of vitamin D deficiency in
      Korean patients with COPD and a significant relationship between vitamin D
      deficiency and airflow limitation. The exercise capacity tended to be decreased
      in the vitamin D deficiency group.

PMID- 25868753
TI  - Individual, Interpersonal, and Structural Power: Associations With Condom Use in
      a Sample of Young Adult Latinos.
AB  - Interviews were conducted with 480 sexually active Latino young adults from four
      rural counties in Oregon. We examined relationships between three levels of power
      (individual, interpersonal, and structural) and consistent condom use. Condom use
      self-efficacy and sexual decision-making, examples of individual and
      interpersonal measures of power, respectively, were associated with increased
      odds of consistent condom use among both men and women. Among men only,
      increasing relationship control, an interpersonal measure of power, was
      associated with lower odds of consistent condom use. Among women only, increasing
      medical mistrust, a structural measure of power, was associated with increased
      odds of consistent condom use. 

PMID- 25868754
TI  - Active Immunization with DNA Vaccine Reduced Cerebral Inflammation and Improved
      Cognitive Ability in APP/PS1 Transgenic Mice by In Vivo Electroporation.
AB  - The aggregation of amyloid beta-peptide (Abeta) is thought to play a pivotal role
      in the disease progression of Alzheimer's disease (AD). Amyloid beta directed
      immunotherapy has been considered an alternative AD treatment. In this study, we
      constructed a DNA vaccine, p(Abeta3-10)10-mIL-4, encoding ten tandem repeats of
      Abeta3-10 fused with mouse IL-4. Eight-month-old APP/PS1 transgenic mice were
      injected intramuscularly with p(Abeta3-10)10-mIL-4 followed by in vivo
      electroporation. Immunization with the vaccine induced high-titer anti-Abeta
      antibodies and attenuated the behavior impairment. Immunoglobulin isotyping
      revealed a predominantly IgG1 response and ex vivo cultured splenocytes exhibited
      a low IFN-gamma and high IL-4 response, indicating a Th2 anti-inflammatory
      response. Immunohistochemical analysis revealed that p(Abeta3-10)10-mIL-4
      immunization decreased Abeta deposition, and the microglial attraction
      significantly decreased accompanied by the clearance of Abeta. There was no
      microhemorrhage in the brain of the immunized mice. These results suggest that
      the immunization potentially reduced the inflammation in brain of transgenic mice
      and therefore improved their cognitive ability. This novel DNA vaccine p(Abeta3
      10)10-mIL-4 may be an effective immunization method as therapy for AD.

PMID- 25868755
TI  - Up-regulation of VCAM1 Relates to Neuronal Apoptosis After Intracerebral
      Hemorrhage in Adult Rats.
AB  - Vascular cell adhesion molecule 1 (VCAM1) is a member of the Immunoglobulin
      superfamily and encodes a cell surface sialoglycoprotein expressed in cytokine
      activated endothelium. This type I membrane protein mediates leukocyte
      endothelial cell adhesion, facilitates the downstream signaling, and may play a
      role in the development of artherosclerosis and rheumatoid arthritis.
      Accumulating evidence has demonstrated that VCAM1 exerts an anti-apoptotic effect
      in several tumor tissues such as ovarian cancer and breast cancer. Intracerebral
      hemorrhage (ICH) is the second most common subtype of stroke with high morbidity
      and mortality, which imposes a big burden on individuals and the whole society.
      These together prompted us to question whether VCAM1 has some association with
      neuron apoptosis during the pathological process of ICH. An ICH rat model was
      established and assessed by behavioral tests in order to explore the role of
      VCAM1 after ICH. Up-regulation of VCAM1 was observed in brain areas surrounding
      the hematoma following ICH by western blotting and immunohistochemistry.
      Immunofluorescence manifested VCAM1 was strikingly increased in neurons, but not
      in astrocytes and microglia. Furthermore, we detected that neuronal apoptosis
      marker active caspase-3 had co-localizations with VCAM1. At the same time, Bcl-2
      was also co-localized with VCAM1. Taken together, our findings suggested that
      VCAM1 might be involved in the neuronal apoptosis and pathophysiology of ICH.

PMID- 25868756
TI  - Chemical biology of anticancer gold(III) and gold(I) complexes.
AB  - Gold complexes have recently gained increasing attention in the design of new
      metal-based anticancer therapeutics. Gold(III) complexes are generally
      reactive/unstable under physiological conditions via intracellular redox
      reactions, and the intracellular Au(III) to Au(I) reduction reaction has recently
      been "traced" by the introduction of appropriate fluorescent ligands. Similar to
      most Au(I) complexes, Au(III) complexes can inhibit the activities of thiol
      containing enzymes, including thioredoxin reductase, via ligand exchange
      reactions to form Au-S(Se) bonds. Nonetheless, there are examples of
      physiologically stable Au(III) and Au(I) complexes, such as [Au(TPP)]Cl (H2TPP =
      5,10,15,20-tetraphenylporphyrin) and [Au(dppe)2]Cl (dppe = 1,2
      bis(diphenylphosphanyl)ethane), which are known to display highly potent in vitro
      and in vivo anticancer activities. In this review, we summarize our current
      understanding of anticancer gold complexes, including their mechanisms of action
      and the approaches adopted to improve their anticancer efficiency. Some recent
      examples of gold anticancer chemotherapeutics are highlighted.

PMID- 25868757
TI  - Child debriefing: a review of the evidence base.
AB  - INTRODUCTION: Debriefing, a controversial crisis intervention delivered in the
      early aftermath of a disaster, has not been well evaluated for use with children
      and adolescents. This report constitutes a review of the child debriefing
      evidence base. METHODS: A systematic search of selected bibliographic databases
      (EBM Reviews, EMBASE, ERIC, Medline, Ovid, PILOTS, PubMed, and PsycINFO) was
      conducted in the spring of 2014 using search terms related to psychological
      debriefing. The search was limited to English language sources and studies of
      youth, aged 0 to 18 years. No time limit was placed on date of publication. The
      search yielded 713 references. Titles and abstracts were reviewed to select
      publications describing scientific studies and clinical reports. Reference
      sections of these publications, and of other literature known to the authors that
      was not generated by the search, were used to locate additional materials. Review
      of these materials generated 187 publications for more thorough examination; this
      assessment yielded a total of 91 references on debriefing in children and
      adolescents. Only 15 publications on debriefing in children and adolescents
      described empirical studies. Due to a lack of statistical analysis of
      effectiveness data with youth, and some articles describing the same study, only
      seven empirical studies described in nine papers were identified for analysis for
      this review. These studies were evaluated using criteria for assessment of
      methodological rigor in debriefing studies. RESULTS: Children and adolescents
      included in the seven empirical debriefing studies were survivors of motor
      vehicle accidents, a maritime disaster, hostage taking, war, or peer suicides.
      The nine papers describing the seven studies were characterized by inconsistency
      in describing the interventions and populations and by a lack of information on
      intervention fidelity. Few of the studies used randomized design or blinded
      assessment. The results described in the reviewed studies were mixed in regard to
      debriefing's effect on posttraumatic stress, depression, anxiety, and other
      outcomes. Even in studies in which debriefing appeared promising, the research
      was compromised by potentially confounding interventions. CONCLUSION: The results
      highlight the small empirical evidence base for drawing conclusions about the use
      of debriefing with children and adolescents, and they call for further dialogue
      regarding challenges in evaluating debriefing and other crisis interventions in
      children.

PMID- 25868758
TI  - Changes in Keratocyte Density and Visual Function Five Years After Laser In Situ
      Keratomileusis: Femtosecond Laser Versus Mechanical Microkeratome.
AB  - PURPOSE: To determine the effects of keratocyte loss on optical properties and
      vision after laser in situ keratomileusis (LASIK) with the flap created with a
      femtosecond laser or a mechanical microkeratome. DESIGN: Randomized clinical
      paired-eye study. METHODS: Both eyes of 21 patients received LASIK for myopia or
      myopic astigmatism. One eye of each patient was randomized by ocular dominance to
      flap creation with a femtosecond laser and the other eye to flap creation with a
      mechanical microkeratome. Before LASIK and at 1, 3, and 6 months and 1, 3, and 5
      years after LASIK, keratocyte density was measured using confocal microscopy, and
      high-contrast visual acuity and anterior corneal wavefront aberrations were
      measured by standard methods. At each visit, all variables were compared between
      methods of creating the flap and to the same variable before treatment using
      paired tests with Bonferroni correction for multiple comparisons. RESULTS:
      Keratocyte density in the flap decreased by 20% during the first year after LASIK
      and remained low through 5 years (P < .001). High-order wavefront aberrations
      increased and uncorrected visual acuity improved immediately after surgery, but
      these variables did not change further to 5 years. There were no differences in
      any variables between treatments. CONCLUSIONS: A sustained reduction in
      keratocyte density does not affect vision or optical properties of the cornea
      through 5 years after LASIK. The method of creating a LASIK flap does not
      influence the changes in keratocyte density in the flap.

PMID- 25868759
TI  - Effects of Dry Eye Therapies on Environmentally Induced Ocular Surface Disease.
AB  - PURPOSE: To evaluate the effectiveness of artificial tears and corticosteroids on
      mitigating the acute ocular surface response to low-humidity environments.
      DESIGN: Single-group, crossover clinical trial. METHODS: Twenty subjects with
      aqueous deficient dry eye were enrolled. Subjects meeting inclusion criteria at
      visit 1 were exposed to a baseline 90-minute low-humidity environment at visit 2.
      They then used artificial tears for 2 weeks prior to low-humidity exposure at
      visit 3, followed by 0.1% dexamethasone for 2 weeks prior to the final low
      humidity exposure at visit 4. Outcome measures included corneal and conjunctival
      staining, blink rate, and irritation symptoms before and after each low-humidity
      exposure. Digital polymerase chain reaction (PCR) was performed to measure HLA-DR
      RNA transcripts in conjunctival cells taken by impression cytology at each visit.
      RESULTS: There was significantly less corneal and conjunctival epitheliopathy
      after the low-humidity exposure at visit 4 compared to after the low-humidity
      exposure at visit 3 (P = .003). Subjects reported significantly less eye
      irritation during the low-humidity exposure after using the dexamethasone (visit
      4) compared to artificial tears (visit 3) (P = .01). HLA-DR transcripts
      significantly decreased after the stress at visit 4 (post dexamethasone) compared
      to visit 2. CONCLUSION: Our study demonstrates that corticosteroid eye drops
      mitigate the acute adverse effects of an experimental low-humidity challenge,
      likely owing to suppression of stress-activated inflammatory pathways. While
      extended use of corticosteroids is not indicated, other anti-inflammatory
      therapies with activity against stress-activated pathways may prove as effective.

PMID- 25868761
TI  - Thoracic outlet and pectoralis minor syndromes endovenous treatment of
      insufficient saphenous vein.

PMID- 25868760
TI  - Frequency Doubling Technology Perimetry and Changes in Quality of Life of
      Glaucoma Patients: A Longitudinal Study.
AB  - PURPOSE: To evaluate the relationship between rates of change on frequency
      doubling technology (FDT) perimetry and longitudinal changes in quality of life
      (QoL) of glaucoma patients. DESIGN: Prospective observational cohort study.
      METHODS: One hundred fifty-two subjects (127 glaucoma and 25 healthy) were
      followed for an average of 3.2 +/- 1.1 years. All subjects were evaluated with
      National Eye Institute Visual Function Questionnaire (NEI VFQ-25), FDT, and
      standard automated perimetry (SAP). Glaucoma patients had a median of 3 NEI VFQ
      25, 8 FDT, and 8 SAP tests during follow-up. Mean sensitivities of the integrated
      binocular visual fields were estimated for FDT and SAP and used to calculate
      rates of change. A joint longitudinal multivariable mixed model was used to
      investigate the association between change in binocular mean sensitivities and
      change in NEI VFQ-25 Rasch-calibrated scores. RESULTS: There was a statistically
      significant correlation between change in binocular mean sensitivity for FDT and
      change in NEI VFQ-25 scores during follow-up in the glaucoma group. In
      multivariable analysis with the confounding factors, each 1 dB/year change in
      binocular FDT mean sensitivity corresponded to a change of 0.8 units per year in
      the NEI VFQ-25 scores (P = .001). For binocular SAP mean sensitivity, each 1
      dB/year change was associated with 2.4 units per year change in NEI VFQ-25 scores
      (P < .001). The multivariable model containing baseline and rate of change
      information from SAP had stronger ability to predict change in NEI VFQ-25 scores
      compared to the equivalent model for FDT (R(2) of 50% and 30%, respectively; P =
      .001). CONCLUSION: SAP performed significantly better than FDT in predicting
      change in NEI VFQ-25 scores in our population, suggesting that it may still be
      the preferable perimetric technique for predicting risk of disability from the
      disease.

PMID- 25868762
TI  - Thoracic outlet and pectoralis minor syndromes.
AB  - Compression of the neurovascular bundle to the upper extremity can occur above or
      below the clavicle; thoracic outlet syndrome (TOS) is above the clavicle and
      pectoralis minor syndrome is below. More than 90% of cases involve the brachial
      plexus, 5% involve venous obstruction, and 1% are associate with arterial
      obstruction. The clinical presentation, including symptoms, physical examination,
      pathology, etiology, and treatment differences among neurogenic, venous, and
      arterial TOS syndromes. This review details the diagnostic testing required to
      differentiate among the associated conditions and recommends appropriate medical
      or surgical treatment for each compression syndrome. The long-term outcomes of
      patients with TOS and pectoralis minor syndrome also vary and depend on duration
      of symptoms before initiation of physical therapy and surgical intervention.
      Overall, it can be expected that >80% of patients with these compression
      syndromes can experience functional improvement of their upper extremity; higher
      for arterial and venous TOS than for neurogenic compression. 

PMID- 25868763
TI  - Update of endovenous treatment modalities for insufficient saphenous veins--a
      review of literature.
AB  - Lower-limb venous insufficiency resulting from saphenous vein incompetence is a
      common disorder, increasing with age. For decades, surgical stripping of the
      great saphenous vein has been the gold standard in varicose vein treatment. The
      desire to optimize outcomes of treatment and reduce surgical trauma has led to
      the development of endovenous techniques. Today, several endovenous techniques
      are available to ablate the saphenous vein segments with abnormal vein valve
      function. In this review, we discuss the techniques, mechanisms of action,
      outcomes, and complications of all endovenous treatment modalities for the
      treatment of symptomatic lower-limb varicose veins. 

PMID- 25868765
TI  - Reduction of Adult Intussusception: More Harm Than Benefit.

PMID- 25868766
TI  - Educational meetings.

PMID- 25868764
TI  - Association of fatty-acid synthase polymorphisms and expression with outcomes
      after radical prostatectomy.
AB  - BACKGROUND: Fatty-acid synthase (FASN), selectively overexpressed in prostate
      cancer (PCa) cells, has been described as linked to the aggressiveness of PCa.
      Constitutional genetic variation of the FASN gene and the expression levels of
      FASN protein in cancer cells could thus be expected to predict outcome after
      radical prostatectomy (RP). This study evaluates the associations of malignant
      tissue status, neoadjuvant androgen deprivation therapy (NADT) and single
      nucleotide polymorphisms (SNPs) of FASN with FASN protein expression in prostate
      tissue. The study then examines the associations of FASN SNPs and gene expression
      with three measures of post-prostatectomy outcome. METHODS: Seven tagging FASN
      SNPs were genotyped in 659 European American men who underwent RP at Roswell Park
      Cancer Institute between 1993 and 2005. FASN protein expression was assessed
      using immunohistochemistry. The patients were followed for an average of 6.9
      years (range: 0.1-20.6 years). Outcome was assessed using three end points:
      biochemical failure, treatment failure and development of distant metastatic PCa.
      Cox proportional hazards analyses were used to evaluate the associations of the
      tagging SNPs and FASN expression with these end points. Bivariate associations
      with outcomes were considered; the associations also were controlled for known
      aggressiveness indicators. RESULTS: Overall, no SNPs were associated with any
      known aggressiveness indicators. FASN staining intensity was stronger in
      malignant than in benign tissue, and NADT was associated with decreased FASN
      staining in both benign and malignant tissue. The relationships of FASN SNPs and
      staining intensity with outcome were less clear. One SNP, rs4246444, showed a
      weak association with outcome. FASN staining intensity also showed a weak and
      seemingly contradictory relationship with outcome. CONCLUSIONS: Additional study
      with longer follow-up and populations that include more metastatic patients is
      warranted.

PMID- 25868767
TI  - Identification and differential diagnosis of perimortem blunt force trauma in
      tubular long bones.
AB  - The identification of perimortem injuries from human remains is crucial in the
      forensic evaluation of skeletal trauma. The purpose of this article is to review
      the criteria currently used by forensic experts for the identification and
      differential diagnosis of perimortem blunt force trauma in long bones. The
      mechanism of injury and the associated fracture pattern in long bones is
      discussed because it is fundamental in the forensic interpretation. The
      distinction between postmortem and perimortem fractures is based on the evidence
      of an osteogenic reaction. The first signs of healing can be detected
      macroscopically, radiographically, or histologically. Perimortem injuries may be
      distinguished from postmortem damage by examining certain attributes such as
      fracture angle and fracture margins. Additionally, the most commonly encountered
      taphonomic factors leading to postmorterm damage are described in order to alert
      the workers of the existence of such pitfalls that may perplex the forensic
      interpretation of skeletal trauma. Although the distinction of bone damage that
      occurred long after death from perimortem trauma is relatively easy, the
      differentiation of fractures inflicted shortly before death or soon after death
      may be difficult or even impossible. 

PMID- 25868768
TI  - Measurement of substance P and met-enkephalin in the serum of violent death
      victims.
AB  - Very often the allocation of putative damages for wrongful death and the
      determination of aggravating factors in the sentencing of an individual convicted
      of homicide by a jury is based on a subjective determination of the amount of
      pain suffered by the victim. This study was designed to determine whether the
      quantitative determination of peptides involved in nociception and inflammation
      offer the potential to provide an objective basis for an assessment of pain prior
      to death. Two peptides. substance P and met-enkephalin, were quantitated using
      radioimmunoassay (RIA) in the serum of 131 autopsy subjects. Cases were selected
      that presented decedents who underwent a violent death resulting in extensive
      trauma to tissue. Only decedents with no known prior clinical manifestation and
      no indication of prior drug use were selected. Of 131 cases selected, 59 died
      from blunt trauma deaths, 47 from gunshot deaths, and 25 from stabbing deaths.
      Cases were selected without regard to whether the death was accidental, or by
      homicide or suicide. Values from cases having similar incident-death time
      intervals were pooled and then compared. Results show that an observable pattern
      exists between the concentrations of substance P and met-enkephalin and the
      incident-death time interval. Data showed that the concentrations of substance P
      and met-enkephalin vary with the incident-death time interval. The amount of
      serum substance P initially increases with increasing incident-death time
      interval but begins to decrease at longer incident-death time intervals. In
      contrast, the serum concentration of met-enkephalin continues to show increased
      concentration as the incident-death time intervals become greater. The Kruskal
      Wallis test was performed to determine the level of significance of the variation
      in both peptide concentrations within four consecutive time intervals. Variation
      in substance P concentration was statistically significant in all comparisons
      performed with 0.01 being the lowest level of significance of any four
      consecutive groups tested. Conversely, intervals encompassing incident-death time
      intervals of 1-2 hours to 5-10 days did not demonstrate significant variation in
      met-enkephalin concentration. However, groups with smaller and larger time
      intervals than the nonsignificant groups did show statistical variation. Although
      owing to a number of variables, a direct correlation between peptide
      concentrations and the level of pain may not be possible, the results of the
      study indicate that a presumption of antemortem pain may be possible with future
      study. 

PMID- 25868769
TI  - Two-tailed delimitation of the time of death by immunohistochemical detection of
      somatostatin and GFAP.
AB  - Delimitating the time of death becomes increasingly difficult and inaccurate, the
      further back it lays in time. To contribute to available techniques, pancreas and
      brain tissue from 500 corpses, whose time of death lay within 1 day and 23 days
      +/-1 day, were immunohistochemically stained with anti-somatostatin and anti
      glial fibrillary acidic protein (GFAP) antibodies. Somatostatin and GFAP are
      recognized as antigen by the employed antibodies. This does not occur when
      proteolytic processes after death disturb the tertiary structure, altering its
      antigen properties. In our cases, stainability of somatostatin in the pancreas
      was always given within 2 days after death. Hence, given a negative
      immunoreaction, death can be assumed to have occurred a minimum of 3 days before
      formaldehyde fixation, which stops the proteolysis. A negative immunoreaction
      occurred consistently after 11 days, indicating that if a positive reaction is
      obtained in a specimen, the death of the respective person must have occurred
      amaximum of 10 days before fixation. GFAP was always stainable in the frontal
      cortex within 3 days after death, which means that in the case of a negative
      immunoreaction, death can be assumed to have occurred a minimum of 4 days before
      fixation. A negative immunoreaction occurred consistently after 14 days,
      indicating that if a positive reaction is obtained in a specimen the death of the
      respective person must have occurred a maximum of 13 days before fixation. The
      presented methods provide further improvements of the possibilities of
      delimitating the time of death, whereby the combination of both methods allows a
      two-tailed delimitation. 

PMID- 25868770
TI  - The histological demonstration of lipids in the proximal renal tubules of
      patients with diabetic coma.
AB  - The Armanni-Ebstein phenomenon is a vacuolization of the cells of the proximal
      kidney tubules in diabetic coma. It has been believed to represent glycogen. In
      the present examination of 14 cases of diabetic coma, high contents of lipids,
      probably triglycerides, were demonstrated in the vacuoles by histological
      staining. Only weak positive reactions were found in diabetic controls. In both
      alcoholic and nonalcoholic-nondiabetics, no lipid was found. The sensivity was
      very high, but it was difficult from the present material to ascertain the level
      of specificity. The authors suggest the term fatty kidney in diabetics. 

PMID- 25868771
TI  - Suicide in our elders : A 10-year review of kentucky medical examiner cases.
AB  - The suicide rate in the United States is consistently higher in the elderly (>-65
      years) than among younger cohorts, reaching approx 5500 deaths in 2002. In this
      article, we present a 10-year (1993-2002) retrospective review of 348 Kentucky
      medical examiner cases ascribed to suicide between 65 and 96 years. Most victims
      were males (86.8%) and Caucasian (98.9%). The predominant cause of death was
      firearm injury (80.7%), followed by hanging (4.9%) and overdose (4.3%). The
      pervasiveness of elderly suicide by firearm requires a multidisciplinary approach
      to the recognition of indicators and the development of strategies for treatment
      and prevention of suicide in at-risk elders. 

PMID- 25868772
TI  - determination of sex in south african blacks by discriminant function analysis of
      mandibular linear dimensions : A preliminary investigation using the zulu local
      population.
AB  - The determination of sex is a critical component in forensic anthropological
      investigation. The literature attests to numerous metrical standards, each
      utilizing diffetent skeletal elements, for sex determination in South A frican
      Blacks. Metrical standards are popular because they provide a high degree of
      expected accuracy and are less error-prone than subjective nonmetric visual
      techniques. We note, however, that there appears to be no established metric
      mandible discriminant function standards for sex determination in this
      population.We report here on a preliminary investigation designed to evaluate
      whether the mandible is a practical element for sex determination in South
      African Blacks. The sample analyzed comprises 40 nonpathological Zulu individuals
      drawn from the R.A. Dart Collection. Ten linear measurements, obtained from
      mathematically trans-formed three-dimensional landmark data, are analyzed using
      basic univariate statistics and discriminant function analyses. Seven of the 10
      measurements examined are found to be sexually dimorphic; the dimensions of the
      ramus are most dimorphic. The sex classification accuracy of the discriminant
      functions ranged from 72.5 to 87.5% for the univariate method, 92.5% for the
      stepwise method, and 57.5 to 95% for the direct method. We conclude that the
      mandible is an extremely useful element for sex determination in this population.

PMID- 25868773
TI  - Antemortem trauma from rodent activity The popiel phenomenon.
AB  - Injuries to bodies from animal activity are often postmortem in nature, although
      differentiating ante- from postmortem tissue damage may be difficult. Presented
      here is the case of a 73-year-old woman who died of a cerebral infarct. The woman
      demonstrated postmortem, and probable premortem, injuries resulting from rodent
      activity. Histological examination of tissues from areas of animal activity
      revealed a subtle early vital reaction, suggesting that the victim may have been
      alive during the animal feeding activity. Given the Polish folk legend of Popiel,
      a ninth-century ruler who was eaten alive by mice, the finding of antemortem
      injuries due to rodents or other animals could be designated the "Popiel
      phenomenon." Histological assessment of such wounds may be a crucial step in
      determining the timing of injuries, helping to elucidate the chronology of the
      fatal event, and separating pre- from postmortem wounds. If a vital reaction is
      detected, it can be assumed that the victim was alive for some time in an
      incapacitated state prior to death, and that death did not occur rapidly. 

PMID- 25868774
TI  - Suicide by an electric power drill.
AB  - Suicide by means of an electric power drill with dual penetration of the anterior
      aspect of the thorax is described. Cause of death was a perforating injury of the
      heart with pericardial tamponade, combined with bleeding into the thoracic cavity
      caused by a perforation of the left lung. Psychiatric background revealed a long
      term depression, in part with psychotic symptoms. 

PMID- 25868775
TI  - Propofol infusion syndrome.
AB  - In this article, we present the case of a previously well 31-year-old man who
      sustained a mild closed-head injury following a motor vehicle incident and was
      admitted to the intensive care unit of a major teaching hospital. The man was
      sedated using propofol combined with midazolam and morphine as the main sedating
      agent. The propofol was started and continued at high dose for 8 days, over which
      time the patient deteriorated with metabolic acidosis, rhabdomyolysis, renal
      impairment, and cardiovascular collapse and then died. A forensic autopsy was
      performed. The only positive autopsy finding was a cardiac perivascular and
      interstitial infiltrate of mononuclear cells. The clinical and pathological
      features in the case presented were consistent with propofol infusion syndrome.
      No other cause for the above features was found and the cause of death was given
      as death related to propofol infusion syndrome.Propofol infusion syndrome is
      characterized by metabolic acidosis, rhadbomyolysis, and myocardial failure,
      sometimes with renal failure and hyperkalemia occurring in the setting of high
      dose propofol treatment. The syndrome has become increasingly recognized in
      recent years. The syndrome is of importance to forensic pathologists who may see
      cases referred to their practice because of the unexplained deterioration of a
      patient in the intensive care unit and the association with head-injured patients
      and the pediatric population. Death associated with propofol infusion has not
      been described in the forensic literature. 

PMID- 25868776
TI  - Sex determination.
AB  - Determing the sex of a give DNA sample can provide criminal investigators with
      useful intelligence and can aid the identification of missing persons and
      disaster victims. Polymerase chain reaction-based systems that amplify regions of
      the am elogenin gene have become the method of choice for sex determination of
      biological samples. This system can, however, result in false female sex
      designation when mutations affect primer binding sites of the Y homolog of this
      target sequence, causing drop out of the Y amplification product. Erroneous sex
      determination could have drastic consequences when applied to forensic situations
      by misdirecting investigators or hindering the identification of deceased
      individuals. Current methods of sex determination are described and possible
      alternative approaches to avoid errors are discussed. 

PMID- 25868778
TI  - British association in forensic medicine summer meeting, penrith, England, july
      2006.

PMID- 25868777
TI  - Ba'alat.

PMID- 25868779
TI  - The impact of visiting student electives on surgical Match outcomes.
AB  - BACKGROUND: Residency applicants commonly complete visiting student electives
      (VSEs) hoping to increase their odds of matching at host institutions. Existing
      evidence on Match outcomes for applicants who complete VSEs is limited. As VSEs
      involve monetary and opportunity costs to students and administrators, data on
      their utility are vital for student well-being, preparedness for residency, and,
      ultimately, success in the Match. We investigated the utilization and impact of
      VSEs for all applicants. We hypothesized that completion of VSEs would increase
      the likelihood of matching at a host institution. MATERIALS AND METHODS: A
      retrospective review was conducted of academic records and National Resident
      Matching Program outcomes for the graduates of one institution and visiting
      students to that institution over the course of 7 y. RESULTS: Utilization of VSEs
      varied significantly among specialties. Across all specialties and in general
      surgery, applicants were more likely to match into host programs than others. The
      size of the effect of VSEs on outcomes varied by specialty. Host programs were
      applicants' top choice for residency in 48% of cases. CONCLUSIONS: Completion of
      VSEs may give surgical applicants increased control over Match outcomes. Our
      findings may assist future students in strategic decision making when determining
      whether and where to use VSEs.

PMID- 25868780
TI  - Peptide spectra in Wilms tumor that associate with adverse outcomes.
AB  - BACKGROUND: The 2013 Children's Oncology Group (COG) blueprint for renal tumor
      research challenges investigators to develop new, risk-specific biological
      therapies for unfavorable histology and higher-risk Wilms tumor (WT) in an effort
      to close a persistent survival gap and to reduce treatment toxicities. As an
      initial response to this call from the COG, we used imaging mass spectrometry to
      determine peptide profiles of WT associated with adverse outcomes. MATERIALS AND
      METHODS: We created a WT tissue microarray containing 2-mm punches of formalin
      fixed, paraffin-embedded specimens archived from 48 sequentially treated WT
      patients at our institutions. Imaging mass spectrometry was performed to compare
      peptide spectra between three patient groups as follows: unfavorable versus
      favorable histology, treatment success versus failure, and COG higher- versus
      lower-risk disease. Statistically significant peptide peaks differentiating
      groups were identified and incorporated into a predictive model using a genetic
      algorithm. RESULTS: One hundred thirty-one peptide peaks were differentially
      expressed in unfavorable versus favorable histology WT (P < 0.05). Two hundred
      three peaks differentiated treatment failure from success (P < 0.05). Seventy-one
      peaks differentiated COG higher-risk disease from the very-low, low, and standard
      risk groups (P < 0.05). These peaks were used to develop predictive models that
      could differentiate among patient groups 98.49%, 94.46%, and 98.55% of the time,
      respectively. Spectral patterns were internally cross-validated using a leave-20%
      out model. CONCLUSIONS: Peptide spectra can discriminate adverse behavior of WT.
      After future external validation and refinement, these models could be used to
      predict WT behavior and to stratify intensity of chemotherapy regimens.
      Furthermore, peptides discovered in the model could be sequenced to identify
      potential risk-specific drug targets.

PMID- 25868781
TI  - Laparoscopic sleeve gastrectomy effects on overactive bladder symptoms.
AB  - BACKGROUND: Morbidly obese patients may experience lower urinary tract symptoms.
      However, most studies focus only on urinary incontinence, with little regard to
      other symptoms as those suggestive for overactive bladder (OAB) syndrome.
      Laparoscopic sleeve gastrectomy (LSG) is commonly used to treat obesity; this
      procedure is effective, safe, and capable of reducing the impact of comorbidities
      associated with severe increase in body weight. Therefore, we investigated if LSG
      improves OAB symptoms in morbidly obese patients. METHODS: We prospectively
      recruited 120 morbidly obese patients (60 men and 60 women), evaluated by history
      taking, comorbidity assessment, physical examination, urinalysis and urine
      culture, renal and pelvic ultrasound, a 3-d voiding diary, and the OAB
      questionnaire short form. Outcomes of these investigations were assessed 7 d
      before and 180 d after LSG was performed. Controls were obese individuals (60 men
      and 60 women) from an LSG waiting list. RESULTS: Symptoms of OAB were common in
      the morbidly obese cohort, affecting more women than men. Compared with untreated
      patients, patients treated with LSG had significantly reduced body mass index 180
      d postoperatively; this outcome was associated with improvement in OAB symptoms,
      whereas no change occurred in untreated controls. CONCLUSIONS: OAB symptoms
      improve in morbidly obese patients successfully treated by LSG.

PMID- 25868782
TI  - Overview of the impact of noninvasive prenatal testing on diagnostic procedures.
AB  - Noninvasive prenatal testing (NIPT) has had a profound influence in the field of
      prenatal diagnosis since the 1997 discovery of cell-free fetal DNA in maternal
      blood. Research has progressed rapidly, with clinical data supporting laboratory
      studies showing that NIPT is highly sensitive and specific for fetal aneuploidy,
      resulting in marked uptake in the high-risk patient population. The superior
      accuracy of NIPT compared with conventional screening methods has led to
      significant decreases in the number of invasive diagnostic procedures, in
      addition to a concomitant decrease in the number of procedure-related fetal
      losses. Yet, NIPT has been described as a 'disruptive innovation' due to the
      considerable changes the technology has commanded on current prenatal screening
      and diagnostic practices. This review summarizes both institutional and global
      experience with NIPT uptake, its effect on reducing diagnostic invasive
      procedures, and the unique challenges that reduced procedural volume may have on
      physician and trainee proficiency, cytogenetic laboratories, and neonatal
      outcome.

PMID- 25868784
TI  - Silibinin combination with arsenic strongly inhibits survival and invasiveness of
      human prostate carcinoma cells.
AB  - Effects of silibinin, a naturally occurring flavanone, on prostate carcinoma
      (PCa) cells in presence of arsenic are not known. Arsenic is clinically approved
      for leukemia treatment; however, studies are not enough to support its role in
      the management of solid tumors. In the present study, we observed that silibinin
      (100 uM) modulated the oxidative status of human PCa DU145 cells exposed to
      arsenic (0.5 or 5 uM) and inhibited cell growth and survival by primarily
      inducing autophagy and apoptosis. The silibinin-arsenic combination also
      inhibited the growth, survival, and clonogenic potential of 22Rv1 PCa cells.
      Silibinin with 0.5 or 5 uM arsenic induced G1 or G2/M phase arrest, respectively,
      and decreased the protein levels of CDK2, -4, and -6 and cyclin D1, D3, and E and
      increased CDK inhibitors p21 and p27. Arsenic alone increased cyclin B1 level and
      Cdc2 kinase activity which were reduced in silibinin combination. Cell motility
      and invasiveness along with expression of MMP-2 and vimentin were suppressed.
      Together, these in vitro findings suggest that in presence of arsenic, silibinin
      strongly inhibits tumorigenic and metastatic potential of PCa cells. 

PMID- 25868783
TI  - Molecular development of chondrichthyan claspers and the evolution of copulatory
      organs.
AB  - The earliest known vertebrate copulatory organs are claspers, paired penis-like
      structures that are associated with evolution of internal fertilization and
      viviparity in Devonian placoderms. Today, only male chondrichthyans possess
      claspers, which extend from posterior pelvic fins and function as intromittent
      organs. Here we report that clasper development from pelvic fins of male skates
      is controlled by hormonal regulation of the Sonic hedgehog (Shh) pathway. We show
      that Shh signalling is necessary for male clasper development and is sufficient
      to induce clasper cartilages in females. Androgen receptor (AR) controls the male
      specific pattern of Shh in pelvic fins by regulation of Hand2. We identify an
      androgen response element (ARE) in the Hand2 locus and present biochemical
      evidence that AR can directly bind the Hand2 ARE. Together, our results suggest
      that the genetic circuit for appendage development evolved an androgen regulatory
      input, which prolonged signalling activity and drove clasper skeletogenesis in
      male fins. 

PMID- 25868785
TI  - Tiny tweaks, big changes: An alternative strategy to empower ethical culture of
      human research in anesthesia (A Taiwan Acta Anesthesiologica Taiwanica-Ethics
      Review Task Force Report).
AB  - For this guidance article, the Ethics Review Task Force (ERTF) of the Journal
      reviewed and discussed the ethics issues related to publication of human research
      in the field of anesthesia. ERTF first introduced international ethics principles
      and minimal requirements of reporting of ethics practices, followed by discussing
      the universal problems of publication ethics. ERTF then compared the
      accountability and methodology of several medical journals in assuring authors'
      ethics compliance. Using the Taiwan Institutional Review Board system as an
      example, ERTF expressed the importance of institutional review board registration
      and accreditation to assure human participant protection. ERTF presented four
      major human research misconducts in the field of anesthesia in recent years. ERTF
      finally proposed a flow-chart to guide journal peer reviewers and editors in
      ethics review during the editorial process in publishing. Examples of template
      languages applied in the Ethics statement section in the manuscript are expected
      to strengthen the ethics compliance of the authors and to set an ethical culture
      for all the stakeholders involved in human research.

PMID- 25868786
TI  - Endoscopic bariatric procedures.
AB  - OPINION STATEMENT: Obesity is a pandemy which affects 600 million adults
      worldwide. Surgery is the only therapy which has been shown effective on the long
      term. Transoral surgery (or endotherapy) is particularly attractive in this group
      of patients and has the potential for offering a less invasive alternative. If
      the only treatment currently available in routine is balloon implantation, which
      is effective at short term but unfortunately associated with weight regain after
      removal in the majority of the cases, other techniques currently under
      development or clinical investigations might fine their place in future treatment
      armamentarium. They include restrictive procedures, involving plicature formation
      or tissue apposition in order to reduce the volume of the stomach, decrease its
      compliance, and favor an early satiety. Other techniques focus on malabsorption,
      either by bypassing the contact of food with the jejunum (a feature which also
      improves type 2 diabetes) or by emptying the stomach after food intake. Several
      techniques also allow performing gastrojejunal anastomoses. These could be
      particularly useful in designing hybrid procedures combining laparoscopic and
      transoral approach resulting in less invasive surgical procedures. Even if,
      currently, none of these techniques can be recommended outside clinical
      protocols, it becomes more and more obvious that some of them will find their
      place in the near future.

PMID- 25868787
TI  - Development of a Donor-Centered Approach to Risk Assessment: Rebalancing
      Nonmaleficence and Autonomy.
AB  - Living kidney donors are often excluded from the shared decision making and
      patient-centered models that are advocated in medical practice. Thresholds for
      acceptable risk vary between transplant centers, and between clinicians and
      donors. Although donor selection committees commonly focus on medical risks,
      potential donors also consider nonmedical risks and burdens, which may alter
      their assessment of an acceptable level of medical risk. Thus, transplant centers
      may encounter ethical tensions between nonmaleficence and respect for donor
      autonomy. A donor-centered model of risk assessment and risk reconciliation would
      integrate the donor's values and preferences in a shared decision about their
      eligibility to donate. This paper argues for shifting to a donor-centered model
      of risk assessment, and presents a research agenda to facilitate the greater
      participation of donors in their own evaluation and approval processes. 

PMID- 25868789
TI  - Dynamic changes of optical aberrations during restoration of optical properties
      of hydrophobic acrylic intraocular lens ejected through cartridge.
AB  - AIM: To evaluate the effect of temperature on the restoration of the optical
      properties of hydrophobic acrylic intraocular lenses (IOLs) after ejection
      through a cartridge into a temperature-controlled water chamber. METHODS: Acrylic
      IOLs (SA60AT; iSert 251; W-60; X-70; and VA-70AD) were loaded into a cartridge
      with viscoelastic material and ejected into a water chamber at 24 degrees C or 34
      degrees C. A wavefront analyser was used to measure the spherical and cylindrical
      powers, and the higher-order aberrations of the optics of the IOLs. The time to
      restore the cylindrical power to within 0.1 dioptres of the baseline power was
      determined. RESULTS: Surface irregularities of the IOLs after ejection were
      detected in the dioptric power maps but not in the higher-order aberration maps.
      The cylindrical power and the astigmatic and coma aberrations recovered
      immediately at 34 degrees C but were delayed at 24 degrees C. The restoration
      time of all IOLs at 24 degrees C was significantly longer than that at 34 degrees
      C (p<0.05). CONCLUSIONS: The dioptric power maps determined by the wavefront
      analyser can detect and follow the restoration of the optical properties of
      hydrophobic acrylic IOLs immediately after ejection. The restoration time was
      dependent on the temperature of the water chamber.

PMID- 25868788
TI  - Incidence and severity of retinopathy of prematurity in Turkey.
AB  - BACKGROUND: The purpose of this study was to estimate the current incidence of
      retinopathy of prematurity (ROP) and the need for treatment in preterm infants in
      Turkey. METHODS: The study included preterm infants who had been screened for ROP
      between 2011 and 2013 in 49 neonatal intensive care units. Infants with birth
      weight (BW) <=1500 g or <=32 weeks' gestational age and those with BW >1500 g or
      >32 weeks' GA with an unstable clinical course were included. The incidence of
      any ROP or severe ROP and treatment modalities were determined. RESULTS: The
      study population included 15 745 preterm infants: 11 803 (75%) with GA <=32
      weeks, and 3942 (25%) with GA >32 weeks. Overall, 30% were found to have any
      stage of ROP, and 5% had severe ROP. Severe ROP was diagnosed in 8.2% of infants
      with BW <=1500 g and 0.6% of infants with BW >1500 g. Of all infants diagnosed
      with ROP, 16.5% needed laser photocoagulation, and 20 patients born at >32 weeks'
      GA required this treatment modality. Vitroretinal surgery was performed in 28
      infants with severe ROP: 23 with GA <=28 weeks and 5 with GA 29-32 weeks.
      CONCLUSIONS: The findings of our study have the important implication that more
      mature babies are at risk of severe ROP requiring treatment. An effective
      programme for detecting and treating ROP should be established in Turkey. TRIAL
      REGISTRATION NUMBER: orcid.org/0000-0002-1329-2167.

PMID- 25868790
TI  - An 8-year retrospective study of cataract surgery and postoperative
      endophthalmitis: injectable intraocular lenses may reduce the incidence of
      postoperative endophthalmitis.
AB  - BACKGROUND/AIMS: Postoperative endophthalmitis (POE) is a rare but potentially
      devastating complication of modern cataract surgery. We examine whether the use
      of injectable intraocular lenses (IOLs) is associated with a lower rate of POE
      after cataract surgery compared with forceps-inserted foldable IOLs. METHODS: A
      single-centre retrospective cohort study of 25 410 cataract operations was
      performed over an 8-year period when standard practice in cataract surgery
      changed from the use of forceps-inserted foldable IOLs to injectable IOLs. Cases
      of POE were identified and the rates compared between the two groups. RESULTS:
      Twelve cases of POE were identified in the study period. The rate of POE was
      significantly lower in the injectable IOL group compared with the forceps
      inserted foldable IOL group (0.008% vs 0.081%, p=0.008). This difference remained
      significant when controlling for posterior capsular rupture and lens material.
      CONCLUSIONS: This study, the largest of its kind to date, supports the use of
      injectable IOLs over forceps-inserted foldable IOLs as a significant measure in
      reducing the risk of POE.

PMID- 25868791
TI  - A new epidescemetic keratoprosthesis: pilot investigation and proof of concept of
      a new alternative solution for corneal blindness.
AB  - PURPOSE: To report the outcomes of a new model of epidescemetic keratoprosthesis
      (Kpro) implanted without total corneal trephination. METHODS: Patients were
      considered for implantation with the new Kpro model (KeraKlear) if they were at
      high risk of failure with standard penetrating keratoplasty (PK) or showed
      conditions with a poor prognosis following PK such as severe chemical injury. We
      used femtosecond laser to create the surgical planes adequate for the purpose of
      the Kpro implantation, and the Kpro was implanted intralamellar in 11 eyes and
      epidescemetical in 4 eyes. Follow-up was between 7 and 21 months and mainly for
      anatomical outcomes and complications. RESULTS: For the intralamellar technique,
      the anatomical outcome was excellent in five eyes with no complications. The
      other six eyes developed complications such as deep corneal inflammatory
      membrane, totally vascularised cornea, extrusion of the Kpro and corneal melting,
      all of which were managed successfully. No eye was lost. For the epidescemetical
      technique, the anatomical outcome was excellent in all four eyes. CONCLUSIONS:
      The new KeraKlear Kpro has proved to be a viable alternative to corneal
      transplantation with potential advantages like decreased risk of endophthalmitis,
      expulsive haemorrhage and worsening glaucoma. KeraKlear Kpro is better tolerated
      and less prone to complications when implanted epidescemetically; cases with poor
      corneal quality are better associated to a lamellar fenestrated donor corneal
      graft, leaving the posterior corneal surface intact and implanting the Kpro
      between.

PMID- 25868792
TI  - Lyme neuroborreliosis: a treatable cause of acute ocular motor disturbances in
      children.
AB  - BACKGROUND: Lyme neuroborreliosis (LNB) designates central nervous system
      involvement caused by the tick-borne spirochaete Borrelia burgdorferi (Bb). The
      present study describes a spectrum of acquired ocular motor disorders in children
      with LNB. METHODS: Six paediatric patients (age 3-15 years) with ocular motor
      symptoms as first manifestations of LNB evaluated by a paediatrician and
      ophthalmologist are presented. Diagnosis was based on new onset ocular motor
      disturbances and detection of cerebrospinal fluid (CSF) pleocytosis and
      intrathecal synthesis of Bb IgM and/or IgG antibodies by lumbar puncture. The
      children were evaluated before and after antibiotic treatment with a follow-up
      time of 1-7 months. Videos were obtained both pre and post treatment in four
      patients. RESULTS: Two children presented with acquired nystagmus, one with
      combined nystagmus and partial sixth nerve palsy, one with partial sixth nerve
      palsy, one with ptosis and one with Adie's pupil. Five of the patients presented
      with severe fatigue, malaise, nausea, headache and fever. Four had recognised a
      tick bite recently, and two developed erythema migrans. Intrathecal synthesis of
      IgM and/or IgG antibodies specific for Bb was positive in all children, and five
      showed CSF pleocytosis. Cerebral MRI or CT of the brain were normal. Treatment
      with intravenous or oral antibiotics produced rapid clinical improvement in five
      of the six children. CONCLUSIONS: LNB can present as acute ocular motor disorders
      in conjunction with fatigue and other clinical manifestations. In endemic areas,
      children with unexplained, acquired ocular motor abnormalities should be
      evaluated for LNB, a treatable medical condition.

PMID- 25868793
TI  - Multiparameter analysis of apoptosis in puromycin-treated Saccharomyces
      cerevisiae.
AB  - In Saccharomyces cerevisiae, a typical apoptotic phenotype is induced by some
      stress factors such as sugars, acetic acid, hydrogen peroxide, aspirin and age.
      Nevertheless, no data have been reported for apoptosis induced by puromycin, a
      damaging agent known to induce apoptosis in mammalian cells. We treated S.
      cerevisiae with puromycin to induce apoptosis and evaluated the percentage of
      dead cells by using Hoechst 33342 staining, transmission electron microscopy
      (TEM) and Annexin V flow cytometry (FC) analysis. Hoechst 33342 fluorescence
      images were processed to acquire parameters to use for multiparameter analysis
      [and perform a principal component analysis, (PCA)]. Cell viability was evaluated
      by Rhodamine 123 (Rh 123) and Acridine Orange microscope fluorescence staining.
      The results show puromycin-induced apoptosis in S. cerevisiae, and the PCA
      analysis indicated that the increasing percentage of apoptotic cells delineated a
      well-defined graph profile. The results were supported by TEM and FC. This study
      gives new insights into yeast apoptosis using puromycin as inducer agent, and PCA
      analysis may complement molecular analysis facilitating further studies to its
      detection. 

PMID- 25868794
TI  - ABCB1 and ABCG2 restrict the brain penetration of a panel of novel EZH2
      Inhibitors.
AB  - Enhancer of Zeste Homolog 2 (EZH2) has emerged as a promising therapeutic target
      for treatment of a broad spectrum of tumors including gliomas. We explored the
      interactions of five novel, structurally similar EZH2 inhibitors (EPZ005687, EPZ
      6438, UNC1999, GSK343 and GSK126) with P-glycoprotein (P-gp/ABCB1) and breast
      cancer resistance protein (BCRP/ABCG2). The compounds were screened by in vitro
      transwell assays and EPZ005687, EPZ-6438 and GSK126 were further tested in vivo
      using wild-type (WT), Abcb1 and/or Abcg2 knockout mice. All EZH2 inhibitors are
      transported by P-gp and BCRP, although in vitro the transporter affinity of
      GSK126 was obscured by very low membrane permeability. Both P-gp and Bcrp1
      restrict the brain penetration of EPZ005687 and GSK126, whereas the brain
      accumulation of EPZ-6438 is limited by P-gp only and efflux of EPZ-6438 was
      completely abrogated by elacridar. Intriguingly, an unknown factor present in all
      knockout mouse strains causes EPZ005687 and EPZ-6438 retention in plasma relative
      to WT mice, a phenomenon not seen with GSK126. In WT mice, the GSK126 tissue-to
      plasma ratio for all tissues is lower than for EPZ005687 or EPZ-6438. Moreover,
      the oral bioavailability of GSK126 is only 0.2% in WT mice, which increases to
      14.4% in Abcb1;Abcg2 knockout mice. These results are likely due to poor membrane
      permeability and question the clinical usefulness of GSK126. Although all tested
      EZH2 inhibitors are substrates of P-gp and BCRP, restricting the brain
      penetration and potential utility for treatment of glioma, EPZ-6438 would be the
      most suitable candidate of this series. 

PMID- 25868795
TI  - Efficient use of a translation start codon in BDNF exon I.
AB  - The brain-derived neurotrophic factor (BDNF) gene contains a number of 5' exons
      alternatively spliced with a common 3' exon. BDNF protein is synthesized from
      alternative transcripts as a prepro-precursor encoded by the common 3' exon IX,
      which has a translation start site 21 bp downstream of the splicing site. BDNF
      mRNAs containing exon I are an exception to this arrangement as the last three
      nucleotides of this exon constitute an in-frame AUG. Here, we show that this AUG
      is efficiently used for translation initiation in PC12 cells and cultured
      cortical neurons. Use of exon I-specific AUG produces higher levels of BDNF
      protein than use of the common translation start site, resulting from a higher
      translation rate. No differences in protein degradation, constitutive or
      regulated secretion were detected between BDNF isoforms with alternative 5'
      termini. As the BDNF promoter preceding exon I is known to be highly regulated by
      neuronal activity, our results suggest that the function of this translation
      start site may be efficient stimulus-dependent synthesis of BDNF protein. The
      brain-derived neurotrophic factor (BDNF) gene contains multiple untranslated 5'
      exons alternatively spliced to one common protein-coding 3' exon. However, exon I
      contains an in-frame ATG in a favorable translation context. Here, we show that
      use of this ATG is associated with more efficient protein synthesis than the
      commonly used ATG in exon IX.

PMID- 25868796
TI  - Regional fat depots and their relationship to bone density and microarchitecture
      in young oligo-amenorrheic athletes.
AB  - CONTEXT: Various fat depots have differential effects on bone. Visceral adipose
      tissue (VAT) is deleterious to bone, whereas subcutaneous adipose tissue (SAT)
      has positive effects. Also, marrow adipose tissue (MAT), a relatively newly
      recognized fat depot is inversely associated with bone mineral density (BMD).
      Bone mass in athletes depends on many factors including gonadal steroids and
      muscle mass. Exercise increases muscle mass and BMD, whereas, estrogen deficiency
      decreases BMD. Thus, the beneficial effects of weight-bearing exercise on areal
      and volumetric BMD (aBMD and vBMD) in regularly menstruating (eumenorrheic)
      athletes (EA) are attenuated in oligo-amenorrheic athletes (OA). Of note, data
      regarding VAT, SAT, MAT and regional muscle mass in OA compared with EA and non
      athletes (C), and their impact on bone are lacking. METHODS: We used (i) MRI to
      assess VAT and SAT at the L4 vertebra level, and cross-sectional muscle area
      (CSA) of the mid-thigh, (ii) 1H-MRS to assess MAT at L4, the proximal femoral
      metaphysis and mid-diaphysis, (iii) DXA to assess spine and hip aBMD, and (iv)
      HRpQCT to assess vBMD at the distal radius (non-weight-bearing bone) and tibia
      (weight-bearing bone) in 41 young women (20 OA, 10 EA and 11 C 18-25 years). All
      athletes engaged in weight-bearing sports for >= 4 h/week or ran >= 20
      miles/week. MAIN OUTCOME MEASURES: VAT, SAT and MAT at L4; CSA of the mid-thigh;
      MAT at the proximal femoral metaphysis and mid-diaphysis; aBMD, vBMD and bone
      microarchitecture. RESULTS: Groups had comparable age, menarchal age, BMI, VAT,
      VAT/SAT and spine BMD Z-scores. EA had higher femoral neck BMD Z-scores than OA
      and C. Fat mass was lowest in OA. SAT was lowest in OA (p = 0.048); L4 MAT was
      higher in OA than EA (p = 0.03). We found inverse associations of (i) VAT/SAT
      with spine BMD Z-scores (r = -0.42, p = 0.01), (ii) L4 MAT with spine and hip BMD
      Z-scores (r = -0.44, p = 0.01; r = -0.36, p = 0.02), and vBMD of the radius and
      tibia (r = -0.49, p = 0.002; r = -0.41, p = 0.01), and (iii) diaphyseal and
      metaphyseal MAT with vBMD of the radius (r <= -0.42, p <= 0.01) and tibia (r <= 
      0.34, p <= 0.04). In a multivariate model including VAT/SAT, L4 MAT and thigh
      CSA, spine and hip BMD Z-scores were predicted inversely by L4 MAT and positively
      by thigh CSA, and total and cortical radius and total tibial vBMD were predicted
      inversely by L4 MAT. VAT/SAT did not predict radius or tibia total vBMD in this
      model, but inversely predicted spine BMD Z-scores. When L4 MAT was replaced with
      diaphyseal or metaphyseal MAT in the model, diaphyseal and metaphyseal MAT did
      not predict aBMD Z-scores, but diaphyseal MAT inversely predicted total vBMD of
      the radius and tibia. These results did not change after adding percent body fat
      to the model. CONCLUSIONS: VAT/SAT is an inverse predictor of lumbar spine aBMD Z
      scores, while L4 MAT is an independent inverse predictor of aBMD Z-scores at the
      spine and hip and vBMD measures at the distal tibia and radius in athletes and
      non-athletes. Diaphyseal MAT independently predicts vBMD measures of the distal
      tibia and radius.

PMID- 25868797
TI  - The effect of SERPINF1 in-frame mutations in osteogenesis imperfecta type VI.
AB  - Osteogenesis imperfecta type VI is caused by mutations in SERPINF1, which codes
      for pigment-epithelium derived factor (PEDF). Most of the reported SERPINF1
      mutations lead to premature termination codons, but three in-frame insertion or
      deletion mutations have also been reported. It is not clear how such in-frame
      mutations lead to OI type VI. In the present study we therefore investigated how
      SERPINF1 in-frame mutations affect the intracellular localization and secretion
      of PEDF. Skin fibroblasts affected by SERPINF1 in-frame mutations transcribed
      SERPINF1 at slightly reduced levels but secretion of PEDF was markedly
      diminished. Two deletions (p.F277del and the deletion of SERPINF1 exon 5) were
      associated with retention of PEDF in the endoplasmic reticulum and a stress
      response in osteoblastic cells. A recurrent in-frame duplication of three amino
      acids (p.Ala91_Ser93dup) appeared to lead to intracellular degradation but no
      retention in the endoplasmic reticulum or stress response. Immunofluorescence
      imaging in transiently transfected osteoblastic MC3T3-E1 cells suggested that
      PEDF affected by in-frame mutations was not transported along the secretory
      pathway. MC3T3-E1 osteoblasts stably overexpressing SERPINF1 with the
      p.Ala91_Ser93dup mutation had decreased collagen type I deposition and
      mineralization. Thus, the assessed homozygous in-frame deletions or insertions
      lead to retention or degradation within cellular compartments and thereby
      interfere with PEDF secretion. 

PMID- 25868798
TI  - Loss of milk fat globule-epidermal growth factor 8 (MFG-E8) in mice leads to low
      bone mass and accelerates ovariectomy-associated bone loss by increasing
      osteoclastogenesis.
AB  - Milk fat globule-epidermal growth factor 8 (MFG-E8) is a glycoprotein that
      controls the engulfment of apoptotic cells and exerts inflammation-modulatory
      effects. Recently, it has been implicated in osteoclastogenesis and the
      pathogenesis of inflammatory periodontal bone loss, but its role in physiological
      bone homeostasis is still not well defined. Here, we evaluated the influence of
      MFG-E8 on osteoblasts and osteoclasts and its impact on bone remodeling in
      healthy and ovariectomized mice as a model for post-menopausal osteoporosis.
      Total and trabecular bone mineral densities at the lumbar spine in 6-week-old MFG
      E8 KO mice were reduced by 11% (p < 0.05) and 17% (p < 0.01), respectively, as
      compared to wild-type (WT) mice. Accordingly, serum levels of the bone formation
      marker P1NP were decreased by 37% (p < 0.01) in MFG-E8 KO mice as were the ex
      vivo mineralization capacity and expression of osteoblast genes (Runx2, alkaline
      phosphatase, osteocalcin) in MFG-E8 KO osteoblasts. In contrast, serum bone
      resorption markers CTX1 and TRAP5b were increased by 30% and 60% (p < 0.05),
      respectively, in MFG-E8 KO mice. Furthermore, bone marrow macrophages from MFG-E8
      KO mice differentiated more effectively into osteoclasts, as compared to WT
      cells. MFG-E8-deficient osteoclasts displayed increased bone resorption ex vivo,
      which could be reversed by the presence of recombinant MFG-E8. To determine the
      significance of the enhanced osteoclastogenesis in MFG-E8 KO mice, we performed
      an ovariectomy, which is associated with bone loss due to increased osteoclast
      activity. Indeed, MFG-E8 KO mice lost 12% more trabecular bone density than WT
      mice after ovariectomy. Together, these data indicate that MFG-E8 controls steady
      state and pathological bone turnover and may therefore represent a new target
      gene in the treatment of bone diseases.

PMID- 25868799
TI  - Sclerostin antibody treatment causes greater alveolar crest height and bone mass
      in an ovariectomized rat model of localized periodontitis.
AB  - INTRODUCTION: Periodontitis and osteoporosis are bone destructive diseases with a
      high prevalence in the adult population. The concomitant presence of osteoporosis
      may be a risk factor of progression of periodontal destruction. We studied the
      effect of sclerostin-neutralizing monoclonal antibody (Scl-Ab) on alveolar bone
      endpoints in an ovariectomized (OVX) rat model of induced experimental
      periodontitis. METHODS: Sixty female, 4-month-old Sprague-Dawley rats underwent
      sham operation or bilateral OVX and were left untreated for 2 months.
      Experimental periodontitis (ligature) was established by placing silk sutures
      subgingival to the right maxillary first and second molar teeth for 4 weeks, and
      feeding the rats food and high-sugar drinking water during this period.
      Thereafter, ligatures were removed and 25mg/kg vehicle or Scl-Ab was administered
      subcutaneously twice weekly for 6 weeks. Rats were randomized into four groups:
      (1) Control (Sham+Vehicle), (2) Sham+Ligature+Vehicle, (3) OVX+Ligature+Vehicle,
      and (4) OVX + Ligature + Scl-Ab. Terminal blood and right maxilla specimens were
      collected for analyses. RESULTS: Group 3 rats showed lower bone volume fraction
      (BVF) of alveolar bone with higher bone resorption and lower bone formation than
      Group 2 rats. Group 4 rats had higher alveolar crest height, as assessed by
      linear distance of cementoenamel junction to the alveolar bone crest and greater
      alveolar bone mass using Micro CT, than Group 3 rats. Significantly higher values
      of mineral apposition rate (MAR) and mineralizing surface/bone surface (MS/BS)
      were also observed in Group 4 rats by analyzing polychrome sequential labeling
      data. Increased serum osteocalcin and osteoprotegerin, and deceased serum
      tartrate-resistant acid phosphatase and CTx-1 illustrate the ability of Scl-Ab to
      increase alveolar bone mass by enhancing bone formation and decreasing bone
      resorption in an animal model of estrogen deficiency osteopenia plus
      periodontitis. CONCLUSION: Scl-Ab could be a potential bone anabolic agent for
      improving alveolar crest height and higher alveolar bone mass in conditions where
      alveolar bone loss in periodontitis is compounded by estrogen deficiency
      osteopenia.

PMID- 25868800
TI  - A review of current murine models of multiple myeloma used to assess the efficacy
      of therapeutic agents on tumour growth and bone disease.
AB  - Pre-clinical in vivo models of multiple myeloma are essential tools for
      investigating the pathophysiology of multiple myeloma and for testing new
      therapeutic agents and strategies prior to their potential use in clinical
      trials. Over the last five decades, several different types of murine models of
      multiple myeloma have been developed ranging from immunocompetent syngeneic
      models, e.g. the 5 T series of myeloma cells, to immunocompromised models
      including the SCID xenograft models, which use human myeloma cell lines or
      patient-derived cells. Other models include hybrid models featuring the
      implantation of SCID mice with bone chips (SCID-hu or SCID-rab) or 3-D bone
      scaffolds (SCID-synth-hu), and mice that have been genetically engineered to
      develop myeloma. Bearing in mind the differences in these models, it is not
      surprising that they reflect to varying degrees different aspects of myeloma.
      Here we review the past and present murine models of myeloma, with particular
      emphasis on their advantages and limitations, characteristics, and their use in
      testing therapeutic agents to treat myeloma tumour burden and bone disease.

PMID- 25868801
TI  - MiR-103 inhibits osteoblast proliferation mainly through suppressing Cav1.2
      expression in simulated microgravity.
AB  - Emerging evidence indicates that microRNAs (miRNAs) play important roles in
      modulating osteoblast function and bone formation. However, the influence of
      miRNA on osteoblast proliferation and the possible mechanisms underlying remain
      to be defined. In this study, we aimed to investigate whether miR-103 regulates
      osteoblast proliferation under simulated microgravity condition through
      regulating Cav1.2, the primary subunit of L-type voltage sensitive calcium
      channels (LTCCs). We first investigated the effect of simulated microgravity on
      osteoblast proliferation and the outcomes clearly demonstrated that the
      mechanical unloading inhibits MC3T3-E1 osteoblast-like cell proliferation. Using
      quantitative Real-Time PCR (qRT-PCR), we provided data showing that miR-103 was
      up-regulated in response to simulated microgravity. In addition, we observed that
      up-regulation of miR-103 inhibited and down-regulation of miR-103 promoted
      osteoblast proliferation under simulated microgravity condition. Furthermore,
      knocking-down or over-expressing miR-103, respectively, up- or down-regulated the
      level of Cav1.2 expression and LTCC currents, suggesting that miR-103 acts as an
      endogenous attenuator of Cav1.2 in osteoblasts under simulated microgravity
      condition. More importantly, we showed that the effect of miR-103 on osteoblast
      proliferation was diminished in simulated microgravity, when co-transfecting miR
      103 mimic or inhibitor with Cav1.2 siRNA. Taken together, our data suggest that
      miR-103 inhibits osteoblast proliferation mainly through suppression of Cav1.2
      expression under simulated microgravity condition. This work may provide a novel
      mechanism of microgravity-induced detrimental effects on osteoblast
      proliferation, identifying miR-103 as a novel possible therapeutic target in bone
      remodeling disorders in this mechanical unloading. 

PMID- 25868803
TI  - Lovastatin production: From molecular basis to industrial process optimization.
AB  - Lovastatin, composed of secondary metabolites produced by filamentous fungi, is
      the most frequently used drug for hypercholesterolemia treatment due to the fact
      that lovastatin is a competitive inhibitor of HMG-CoA reductase. Moreover, recent
      studies have shown several important applications for lovastatin including
      antimicrobial agents and treatments for cancers and bone diseases. Studies
      regarding the lovastatin biosynthetic pathway have also demonstrated that
      lovastatin is synthesized from two-chain reactions using acetate and malonyl-CoA
      as a substrate. It is also known that there are two key enzymes involved in the
      biosynthetic pathway called polyketide synthases (PKS). Those are characterized
      as multifunctional enzymes and are encoded by specific genes organized in
      clusters on the fungal genome. Since it is a secondary metabolite, cultivation
      process optimization for lovastatin biosynthesis has included nitrogen limitation
      and non-fermentable carbon sources such as lactose and glycerol. Additionally,
      the influences of temperature, pH, agitation/aeration, and particle and inoculum
      size on lovastatin production have been also described. Although many reviews
      have been published covering different aspects of lovastatin production, this
      review brings, for the first time, complete information about the genetic basis
      for lovastatin production, detection and quantification, strain screening and
      cultivation process optimization. Moreover, this review covers all the
      information available from patent databases covering each protected aspect during
      lovastatin bio-production. 

PMID- 25868802
TI  - Serum FGF-21 levels are associated with worsened radial trabecular bone
      microarchitecture and decreased radial bone strength in women with anorexia
      nervosa.
AB  - BACKGROUND: Anorexia nervosa (AN) is a psychiatric disorder characterized by self
      induced starvation and low body weight. Women with AN have impaired bone
      formation, low bone mass and an increased risk of fracture. FGF-21 is a hormone
      secreted by the liver in starvation and FGF-21 transgenic mice have significant
      bone loss due to an uncoupling of bone resorption and bone formation. We
      hypothesized that FGF-21 may contribute to the low bone mass state of AN.
      SUBJECTS AND METHODS: We studied 46 women: 20 with AN (median age [interquartile
      range]: 27.5 [25, 30.75] years) and 26 normal-weight controls (NWC) of similar
      age (25 [24, 28.5] years). We investigated associations between serum FGF-21 and
      1) aBMD measured by dual energy X-ray absorptiometry, 2) parameters of bone
      microarchitecture in the distal radius and tibia measured by high-resolution
      peripheral quantitative CT and 3) bone strength, estimated by microfinite element
      analysis. RESULTS: FGF-21 levels were similar in AN and NWC (AN: 33.1 [18.1,
      117.0] pg/ml vs. NWC: 57.4 [23.8, 107.1] pg/ml; p = 0.54). There was a
      significant inverse association between log FGF-21 and trabecular number in the
      radius in both AN (R = -0.57, p < 0.01) and NWC (R=-0.53, p < 0.01) and a
      significant positive association between log FGF-21 and trabecular separation in
      the radius in AN (R = 0.50, p < 0.03) and NWC (R = 0.52, p < 0.01). Estimates of
      radial bone strength were inversely associated with log FGF-21 in AN (R = -0.50,
      p < 0.03 for both stiffness and failure load). There were no associations between
      FGF-21 and aBMD, cortical parameters or tibial parameters in the AN or NWC
      groups. CONCLUSIONS: FGF-21 may be an important determinant of trabecular
      skeletal homeostasis in AN.

PMID- 25868804
TI  - Dendritic core-shell systems as soft drug delivery nanocarriers.
AB  - Unimolecular micelles are covalently bound molecular architectures and therefore
      highly stable which makes them particularly attractive for drug delivery.
      Accordingly, many reports in the literature emphasize the importance of these
      molecular architectures for nanomedicine. This conceptual review will present
      some of the recent advances in the application of these dendritic core-shell
      systems for drug delivery. Unimolecular micelles based on hyperbranched and
      dendritic cores will be discussed and sorted by the nature of their core and
      structure. 

PMID- 25868805
TI  - Modularization of genetic elements promotes synthetic metabolic engineering.
AB  - In the context of emerging synthetic biology, metabolic engineering is moving to
      the next stage powered by new technologies. Systematical modularization of
      genetic elements makes it more convenient to engineer biological systems for
      chemical production or other desired purposes. In the past few years, progresses
      were made in engineering metabolic pathway using synthetic biology tools. Here,
      we spotlighted the topic of implementation of modularized genetic elements in
      metabolic engineering. First, we overviewed the principle developed for
      modularizing genetic elements and then discussed how the genetic modules advanced
      metabolic engineering studies. Next, we picked up some milestones of engineered
      metabolic pathway achieved in the past few years. Last, we discussed the rapid
      raised synthetic biology field of "building a genome" and the potential in
      metabolic engineering. 

PMID- 25868806
TI  - The ups and downs of early mothering.
AB  - INTRODUCTION: The maternal experience of having a young infant is often viewed
      through a negative lens focused on psychological distress due, in part, to a
      historical focus on identifying threats to prenatal, perinatal and postpartum
      well-being of women and infants. This report examines maternal appraisal of both
      positive and negative experiences during and after pregnancy and introduces a new
      scale that assesses both uplifts and hassles that are specific to early
      motherhood. METHODS: The sample included 136 women who began study participation
      during pregnancy and completed an existing scale designed to evaluate pregnancy
      specific hassles and uplifts. When infants were 6 months old, participants
      completed the newly developed Maternal Experience Scale (MES) along with
      questionnaires related to anxiety, depression, attachment, parenting stress and
      infant temperament characteristics. RESULTS: In general, women with 6-month-old
      infants rated their maternal experiences far more positively than negatively. MES
      hassles and uplift scores reflected both convergent and discriminant validity
      with general measures of psychological well-being and parent-specific measures.
      Appraisal of the pregnancy experience significantly predicted appraisal of early
      motherhood for hassles, uplifts and a composite score reflecting emotional
      valence. Women became relatively more uplifted and less hassled from pregnancy to
      6-month postpartum; this was particularly true for multiparous women. DISCUSSION:
      The maternal perception of motherhood corresponds to her perception of pregnancy.
      The MES provides a balanced view of motherhood by including maternal appraisal of
      the uplifting aspects of caring for an infant.

PMID- 25868807
TI  - Cognitive workload changes for nurses transitioning from a legacy system with
      paper documentation to a commercial electronic health record.
AB  - OBJECTIVE: Healthcare institutions worldwide are moving to electronic health
      records (EHRs). These transitions are particularly numerous in the US where
      healthcare systems are purchasing and implementing commercial EHRs to fulfill
      federal requirements. Despite the central role of EHRs to workflow, the cognitive
      impact of these transitions on the workforce has not been widely studied. This
      study assesses the changes in cognitive workload among pediatric nurses during
      data entry and retrieval tasks during transition from a hybrid electronic and
      paper information system to a commercial EHR. MATERIALS AND METHODS: Baseline
      demographics and computer attitude and skills scores were obtained from 74
      pediatric nurses in two wards. They also completed an established and validated
      instrument, the NASA-TLX, that is designed to measure cognitive workload; this
      instrument was used to evaluate cognitive workload of data entry and retrieval.
      The NASA-TLX was administered at baseline (pre-implementation), 1, 5 and 10
      shifts and 4 months post-implementation of the new EHR. RESULTS: Most nurse
      participants experienced significant increases of cognitive workload at 1 and 5
      shifts after "go-live". These increases abated at differing rates predicted by
      participants' computer attitudes scores (p = 0.01). CONCLUSIONS: There is
      substantially increased cognitive workload for nurses during the early phases (1
      5 shifts) of EHR transitions. Health systems should anticipate variability across
      workers adapting to "meaningful use" EHRs. "One-size-fits-all" training
      strategies may not be suitable and longer periods of technical support may be
      necessary for some workers.

PMID- 25868808
TI  - Requirements for clinical information modelling tools.
AB  - OBJECTIVE: This study proposes consensus requirements for clinical information
      modelling tools that can support modelling tasks in medium/large scale
      institutions. Rather than identify which functionalities are currently available
      in existing tools, the study has focused on functionalities that should be
      covered in order to provide guidance about how to evolve the existing tools.
      METHODOLOGY: After identifying a set of 56 requirements for clinical information
      modelling tools based on a literature review and interviews with experts, a
      classical Delphi study methodology was applied to conduct a two round survey in
      order to classify them as essential or recommended. Essential requirements are
      those that must be met by any tool that claims to be suitable for clinical
      information modelling, and if we one day have a certified tools list, any tool
      that does not meet essential criteria would be excluded. Recommended requirements
      are those more advanced requirements that may be met by tools offering a superior
      product or only needed in certain modelling situations. RESULTS: According to the
      answers provided by 57 experts from 14 different countries, we found a high level
      of agreement to enable the study to identify 20 essential and 21 recommended
      requirements for these tools. CONCLUSIONS: It is expected that this list of
      identified requirements will guide developers on the inclusion of new basic and
      advanced functionalities that have strong support by end users. This list could
      also guide regulators in order to identify requirements that could be demanded of
      tools adopted within their institutions.

PMID- 25868809
TI  - Influence of weather conditions on the frequent onset of acute myocardial
      infarction.
AB  - BACKGROUND: This study was conducted to clarify the influence of weather
      conditions on the onset of acute myocardial infarction (AMI) in Kumamoto.
      METHODS: We studied 642 consecutive patients (males 433, females 209; 71+/-13
      years) who were admitted with AMI. Days of frequent onset (F-days) were defined
      as days on which >=2 patients had been admitted for AMI, whereas days of non
      frequent onset (N-days) indicated those with fewer than 2 admissions for AMI.
      Meteorological factors, including the mean atmospheric pressure and rainfall, the
      mean, maximum, and minimum temperature, intra-day temperature difference,
      humidity, wind speed, and the number of sunlight hours, were analyzed. All
      variables were measured on the day of onset of AMI and on each of the 2 days
      immediately prior to the day of onset. RESULTS: There were 86 F-days and 1740 N
      days. F-days were significantly associated with lower air temperature (mean,
      maximum, and minimum), higher intra-day temperature difference, lower humidity,
      and longer daily duration of sunlight compared with N-days. In addition,
      meteorological factors for frequent onset of AMI affected older subjects to a
      greater extent than either young or female subjects. Multiple logistic regression
      analysis showed that minimum temperature two days before onset was associated
      with the frequent onset of AMI (odds ratio, 0.805; p<0.05). CONCLUSION: Lower
      minimum temperature on the 2nd day preceding the onset is an independent risk
      factor for the frequent onset of AMI. The association between low ambient
      temperature and frequent onset of AMI was stronger in elderly and female
      subjects.

PMID- 25868810
TI  - Multiple-herbicide resistance in Echinochloa crus-galli var. formosensis, an
      allohexaploid weed species, in dry-seeded rice.
AB  - Biotypes of Echinochloa crus-galli var. formosensis with resistance to cyhalofop
      butyl, an acetyl-CoA carboxylase (ACCase) inhibitor, have been found in dry
      seeded rice fields in Okayama, Japan. We collected two lines with suspected
      resistance (Ecf27 and Ecf108) from dry-seeded rice fields and investigated their
      sensitivity to cyhalofop-butyl and other herbicides. Both lines exhibited
      approximately 7-fold higher resistance to cyhalofop-butyl than a susceptible
      line. Ecf108 was susceptible to penoxsulam, an acetolactate synthase (ALS)
      inhibitor. On the other hand, Ecf27 showed resistance to penoxsulam and two other
      ALS inhibitors: propyrisulfuron and pyriminobac-methyl. The alternative
      herbicides butachlor, thiobencarb, and bispyribac-sodium effectively controlled
      both lines. To examine the molecular mechanisms of resistance, we amplified and
      sequenced the target-site encoding genes in Ecf27, Ecf108, and susceptible lines.
      Partial sequences of six ACCase genes and full-length sequences of three ALS
      genes were examined. One of the ACCase gene sequences encodes a truncated
      aberrant protein due to a frameshift mutation in both lines. Comparisons of the
      genes among Ecf27, Ecf108, and the susceptible lines revealed that none of the
      ACCases and ALSs in Ecf27 and Ecf108 have amino acid substitutions that are known
      to confer herbicide resistance, although a single amino acid substitution was
      found in each of three ACCases in Ecf108. Our study reveals the existence of a
      multiple-herbicide resistant biotype of E. crus-galli var. formosensis at
      Okayama, Japan that shows resistance to cyhalofop-butyl and several ALS
      inhibitors. We also found a biotype that is resistant only to cyhalofop-butyl
      among the tested herbicides. The resistance mechanisms are likely to be non
      target-site based, at least in the multiple-herbicide resistant biotype. 

PMID- 25868811
TI  - Molecular basis for resistance to ACCase-inhibiting herbicides in
      Pseudosclerochloa kengiana populations.
AB  - Pseudosclerochloa kengiana is a troublesome annual grass weed of wheat fields in
      the rice-wheat double cropping areas in China. Resistance has evolved in P.
      kengiana under continuously selective pressure of ACCase-inhibiting herbicides.
      Whole-plant experiments showed that two suspected resistant populations 12-SD-12
      and 12-SD-13 were highly resistant to fenoxaprop-P-ethyl (69.9- and 57.2-fold);
      moderately resistant to clodinafop-propargyl (5.9- and 4.1-fold) and pinoxaden
      (4.4- and 3.5-fold); lowly resistant to fluazifop-P-butyl (2.2- and 2.0-fold) and
      sethoxydim (1.8- and 1.6-fold), but were sensitive to clethodim (1.0- and 0.9
      fold) and mesosulfuron-methyl (1.1- and 0.9-fold). Molecular analyses confirmed
      that a Trp1999 to Ser mutation was present in the resistant populations. Two
      dCAPS markers were also developed to positively determine the wild type Trp and
      mutant Ser alleles at ACCase position 1999. All 350 individual plants of 12-SD-12
      population analysed were heterozygous mutants. Meanwhile, 318 mutant
      heterozygotes and 32 wild types were detected from the 12-SD-13 population. In
      addition, the analysis of plant genotype and phenotype showed that all wild type
      plants were killed after treatment with any one of the ACCase-inhibiting
      herbicides used, while individual plants carrying the W1999S mutation survived
      except when treated with clethodim. To our knowledge, this is the first report of
      pinoxaden resistance and a Trp-1999-Ser mutation in the plastid ACCase for P.
      kengiana. 

PMID- 25868812
TI  - Comparative efficacy of piperine and curcumin in deltamethrin induced splenic
      apoptosis and altered immune functions.
AB  - Deltamethrin (DLM) being a potent immunotoxicant affects both humoral and cell
      mediated immunity. Thus, for the amelioration of its effects, two different
      bioactive herbal extracts piperine and curcumin are evaluated and their efficacy
      has been compared. The docking results demonstrated that curcumin has good
      binding affinity towards CD28 and CD45 receptors as compared to piperine but in
      vitro studies revealed that piperine is more effective. DLM induced apoptotic
      markers such as oxidative stress and caspase 3 have been attenuated more
      significantly by piperine as compared to curcumin. Phenotypic and cytokine
      changes have also been mitigated best with piperine. Thus, these findings
      strongly demonstrate that piperine displays the more anti-oxidative, anti
      apoptotic and chemo-protective properties in the DLM induced splenic apoptosis as
      compared to curcumin. So, piperine can be considered the drug of choice under
      immunocompromised conditions. 

PMID- 25868813
TI  - Ameliorative effects of phycocyanin against gibberellic acid induced
      hepatotoxicity.
AB  - Gibberellic acid (GA3) was used extensively unaware in agriculture in spite of
      its dangerous effects on human health. The current study was designed to
      investigate the ameliorative effects of the co-administration of phycocyanin with
      GA3 induced oxidative stress and histopathological changes in the liver. Forty
      male albino rats were randomly divided into four groups. Group I (control group)
      received normal saline for 6 weeks, Group II (GA3 treated group) received 3.85
      mg/kg body weight GA3 once daily for 6 weeks, Group III (phycocyanin treated
      group) received Phycocyanin 200 mg/kg body weight/day for 6 weeks orally
      dissolved in distilled water and Group IV was treated with GA3 and phycocyanin at
      the same doses as groups 2 and 3. All treatments were given daily using intra
      gastric intubation and continued for 6 weeks. Our results revealed significant
      downregulation of antioxidant enzyme activities and their mRNA levels (CAT, GPx
      and Cu-Zn, SOD) with marked elevation of liver enzymes and extensive fibrous
      connective tissue deposition with large biliary cells in hepatic tissue of GA3
      treated rats, while treatment with phycocyanin improved the antioxidant defense
      system, liver enzymes and structural hepatocytes recovery in phycocyanin treated
      group with GA3. These data confirm the antioxidant potential of Phycocyanin and
      provide strong evidence to support the co-administration of Phycocyanin during
      using GA3. 

PMID- 25868814
TI  - Expression characteristics of two novel cytochrome P450 genes involved in
      fenpropathrin resistance in Tetranychus cinnabarinus (Boisduval).
AB  - The carmine spider mite, Tetranychus cinnabarinus, which is also considered as
      the red form of Tetranychus urticae, is one of the most serious mite pests on
      crops. It is capable of rapidly developing resistance to acaricides, and has
      caused difficulty in controlling. However, the resistance mechanism of this mite
      remains unclear at molecular level. As a member of main detoxification enzymes,
      cytochrome P450 monooxygenases (CYPs or P450s) play important roles in the
      development of acaricide resistance in arthropods. In this study, two novel P450
      genes (CYP389B1 and CYP392A26) were identified and characterized from T.
      cinnabarinus. The opening reading frames (ORFs) of CYP389B1 and CYP392A26
      contained 1545 and 1488 nucleotides, which encode 514 and 495 amino acids,
      respectively. Phylogenetic analysis showed that CYP389B1 and CYP392A26 were most
      closely related to CYP389B1 and CYP392A4 from T. urticae, respectively. When
      treated with piperonyl butoxide (PBO), an inhibitor of P450s, the resistance
      ratio of fenpropathrin-resistant (FeR) strain decreased from 101- to 75-fold,
      which suggested a correlation between P450 and fenpropathrin-resistance in T.
      cinnabarinus. Furthermore, constitutive over-expressions of CYP389B1 and
      CYP392A26 were detected in FeR strain. Meanwhile, the expressions of CYP389B1 and
      CYP392A26 were inducible in FeR strain after treatment in 6, 12 and 24 h with
      LC30 of fenpropathrin; especially, the expression of CYP392A26 increased to a
      markedly high level (20.88-fold higher than in the control) after treatment in 6
      h. However, there was no significant difference between treatment and control in
      susceptible strain. Furthermore, stage specific expression profiles of these two
      genes did not show significant difference among developing stages, except for
      eggs, in which the mRNA levels were quite low. The results indicate that CYP389B1
      and CYP392A26 were involved in the fenpropathrin-resistance in T. cinnabarinus,
      and the expression of CYP392A26 was more sensitive to fenpropathrin stress. These
      findings provide clues for further elucidating the function and regulation
      mechanism of these two cytochrome P450 genes in T. cinnabarinus. 

PMID- 25868815
TI  - Genetics and preliminary mechanism of chlorpyrifos resistance in Phenacoccus
      solenopsis Tinsley (Homoptera: Pseudococcidae).
AB  - Cotton mealybug, Phenacoccus solenopsis Tinsley, is a serious pest of cotton and
      other crops and infestation by this pest results in yield losses that affect the
      economy of Pakistan. Various groups of insecticides have been used to control
      this pest but resistance development is a major factor that inhibits its control
      in the field. Chlorpyrifos is a common insecticide used against many pests
      including P. solenopsis. The present experiment was designed to assess the
      genetics and mechanism of chlorpyrifos resistance and to develop a better
      resistance management strategy and assess the genetics and mechanism of
      chlorpyrifos resistance. Before selection, the field strain showed 3.1-fold
      resistance compared to the susceptible strain (CSS). After 8 rounds of selection
      with chlorpyrifos, a selected population developed a 191.0-fold resistance
      compared to the CSS. The LC50 values of F1 (CRR ? * CSS ?) and F1(?) (CRR ? * CSS
      ?) strains were not significantly different and dominance (DLC) values were 0.42
      and 0.55. Reciprocal crosses between chlorpyrifos susceptible and resistant
      strains indicated that resistance was autosomal and incompletely recessive. The
      monogenic model of fit test and calculation of number of genes segregating in the
      chlorpyrifos resistant strain demonstrated that resistance is controlled by
      multiple genes. A value of 0.59 was calculated for realized heritability for
      chlorpyrifos resistance. Synergism bioassays with piperonyl butoxide and S, S, S
      butyl phosphorotrithioate showed that chlorpyrifos resistance was associated with
      microsomal oxidases and esterases. It was concluded that chlorpyrifos resistance
      in P. solenopsis was autosomally inherited, incompletely recessive and polygenic.
      These findings would be helpful to improve the management of P. solenopsis. 

PMID- 25868816
TI  - Biochemical biomarkers of sublethal effects in Rhinella arenarum late gastrula
      exposed to the organophosphate chlorpyrifos.
AB  - We determined the biochemical and molecular effects of the organophosphate
      insecticide chlorpyrifos (CPF) in the late gastrula embryonic stage of the South
      American toad Rhinella arenarum continuously exposed from fertilization (24 h).
      Our objective was to evaluate these responses as potential biomarkers at low,
      sublethal levels of the toxicant. We first established the EC50 for embryo arrest
      in 21.3 mg/L, with a LOEC of 16 mg/L. At 4 mg/L CPF, some embryos were unable to
      complete the dorsal lip of the blastopore and the yolk plug became blur, probably
      because of abnormal cell migration. Acetylcholinesterase activity, the specific
      biomarker for organophosphates, was unaffected by any of the tested
      concentrations of CPF (2-14 mg/L). In turn, 2 mg/L CPF increased the reduced
      glutathione levels and inhibited glutathione-S-transferase activity, suggesting
      an oxidative stress and antioxidant response. Catalase was induced by CPF
      exposure at higher concentrations (8 and 14 mg/L). We also studied transcription
      factor c-Fos as a signaling event related to development in early embryogenesis.
      Analysis of nuclear c-Fos protein showed two bands, both enhanced in embryos
      exposed to 2 and 8 mg/L CPF. While nuclear Erk protein was practically
      unaffected, Mek protein levels were induced by the OP. Transcription factor c-Fos
      may be then linking oxidative stress with developmental alterations observed due
      to CPF exposure. These molecular and biochemical responses observed in R.
      arenarum gastrula at sublethal CPF exposures may replace non-responsive AChE as
      very early biomarkers in toad gastrula. 

PMID- 25868817
TI  - Characterization of the transcriptome of the Asian gypsy moth Lymantria dispar
      identifies numerous transcripts associated with insecticide resistance.
AB  - Although the Asian gypsy moth Lymantria dispar causes extensive forest damage
      worldwide, little is known regarding the genes involved in its development or
      response to insecticides. Accordingly, characterization of the transcriptome of
      L. dispar larvae would promote the development of toxicological methods for its
      control. RNA-seq analysis of L. dispar larvae messenger RNA (mRNA) generated
      62,063 unigenes with N50 of 993 bp, from which 23,975 unique sequences (E-value <
      10(-5)) were identified using a BLASTx search of the NCBI non-redundant (nr)
      database. Using functional classification in the Gene Ontology (GO) and Clusters
      of Orthologous Groups (COG) databases, 7,309 indentified sequences were
      categorized into 51 functional groups and 8,079 sequences were categorized into
      25 functional groups, respectively. Moreover, we identified a large number of
      transcripts encoding known insecticide targets, or proteins involved in the
      metabolism of insecticides. Reads per kilobase of unigene length per million
      mapped reads (RPKM) analysis identified 39 high abundance transcripts, of which
      27 exhibited significantly altered expression patterns across the egg, larvae,
      pupae, male and female adult stages. Our study provides the most comprehensive
      transcriptomic sequence resource for L. dispar, which will form the basis for
      future identification of candidate insecticide resistance genes in L. dispar. 

PMID- 25868818
TI  - Dichlorvos-induced toxicity in HCT116 cells: involvement of oxidative stress and
      apoptosis.
AB  - Organophosphorous (OP) pesticides are widely used in the agriculture and home.
      Among those pesticides, Dichlorvos (DDVP) is a worldwide used insecticide for
      pest control. DDVP is commonly used as an insecticide for maintenance and growth
      of agricultural products, to control the internal and external parasites of farm
      animals, and to eradicate insects threatening the household, public health, and
      stored products. Although substantial information is available regarding the
      environmental and ecological impact of DDVP, not much is known in regard to its
      toxicity in the mammalian system. Therefore a study was conducted for the
      assessment of cytotoxic and genotoxic effects of DDVP in human colon carcinoma
      (HCT116) cell line. We demonstrated that DDVP significantly decreased cell
      viability as assessed by the MTT assay. The increase in cell death was
      accompanied by a reduction in the mitochondrial membrane potential. Besides,
      pretreatment with Z-VAD-FMK, a general caspases inhibitor, decreased
      significantly the DDVP-induced cell death. We also shown that DDVP induced
      reactive oxygen species (ROS) generation followed by lipid peroxidation as
      evidenced by an increase in the MDA levels. Our results also indicate that DDVP
      induced a concentration-dependent increase in DNA damage as evident by the comet
      assay. These data indicate that DDVP produces cytotoxicity and DNA damage in
      mammalian cells and should be used with caution. 

PMID- 25868819
TI  - Mechanism, stability and fitness cost of resistance to pyriproxyfen in the house
      fly, Musca domestica L. (Diptera: Muscidae).
AB  - Pyriproxyfen, a bio-rational insecticide, used worldwide for the management of
      many insect pests including the house fly, Musca domestica. To devise a
      retrospective resistance management strategy, biological parameters of
      pyriproxyfen resistant (Pyri-SEL), unselected (UNSEL), Cross1 and Cross2M.
      domestica strains were studied in the laboratory. Additionally, the stability and
      mechanism of resistance was also investigated. After 30 generations of
      pyriproxyfen selection, a field-collected strain developed 206-fold resistance
      compared with susceptible strain. Synergists such as piperonyl butoxide and S,S,S
      tributylphosphorotrithioate did not alter the LC50 values, suggesting another
      cause of target site resistance to pyriproxyfen in the Pyri-SEL strain. The
      resistance to all tested insecticides was unstable in Pyri-SEL strain. The
      relative fitness of 0.51 with lower fecundity, hatchability, lower number of next
      generation larvae, reduced mean population growth rate and net reproductive rate
      were observed in the Pyri-SEL strain compared with the UNSEL strain. The cost of
      fitness associated with pyriproxyfen resistance was evident in Pyri-SEL strain.
      The present study provides useful information for making pro-active resistance
      management strategies to delay resistance development. 

PMID- 25868820
TI  - Proteomics-based identification and analysis proteins associated with
      spirotetramat tolerance in Aphis gossypii Glover.
AB  - Spirotetramat were now widely used for control insecticides resistant aphids
      since 2011 in China. In order to elucidate the possible resistance mechanism, a
      laboratory selected resistant strain (SR) of cotton aphid was established with a
      578.93-fold and 14.91-fold resistance ratio to spirotetramat for adult aphids and
      nymph, respectively, as compared with the susceptible strain (SS). In this study,
      a comparative proteomic analysis between SR and SS strains were conducted aims to
      better understand the resistant cotton aphids' spirotetramat tolerance mechanism.
      Approximately 493 protein spots were detected in the two-dimension polyacrylamide
      gel electrophoresis (2-DE). The intensities of 35 protein spots significantly
      changed, showing differences more than 2-fold in the SR strain compared with that
      in the SS strain. Of these spots, 20 protein spots were more abundant in the SR
      strain and 15 protein spots were more abundant in the SS strain. Twenty six
      differently expressed proteins were identified and categorized into several
      functional groups including carbohydrate and energy metabolism, antioxidant
      system, protein folding, amino acid metabolism, secondary metabolism and
      cytoskeleton protein, etc. Among these proteins, the acetyl-coA carboxylase
      (ACC), heat shock protein 70, ubiquitin-conjugating enzyme, fatty acid synthase,
      UDP-glucose 6-dehydrogenase, etc. are speculated confer the spirotetramat
      resistance in cotton aphids. 

PMID- 25868821
TI  - Fipronil induces apoptosis through caspase-dependent mitochondrial pathways in
      Drosophila S2 cells.
AB  - Fipronil is the first phenylpyrazole insecticide widely used in controlling
      pests, including pyrethroid, organophosphate and carbamate insecticides. It is
      generally accepted that fipronil elicits neurotoxicity via interactions with GABA
      and glutamate receptors, although alternative mechanisms have recently been
      proposed. This study evaluates the genotoxicity of fipronil and its likely mode
      of action in Drosophila S2 cells, as an in vitro model. Fipronil administrated
      the concentration- and time-dependent S2 cell proliferation. Intracellular
      biochemical assays showed that fipronil-induced S2 cell apoptosis coincided with
      a decrease in the mitochondrial membrane potential and an increase reactive
      oxygen species generation, a significant decrease of Bcl-2 and DIAP1, and a
      marked augmentation of Cyt c and caspase-3. Because caspase-3 is the major
      executioner caspase downstream of caspase-9 in Drosophila, enzyme activity assays
      were used to determine the activities of caspase-3 and caspase-9. Our results
      indicated that fipronil effectively induced apoptosis in Drosophila S2 cells
      through caspase-dependent mitochondrial pathways. 

PMID- 25868822
TI  - Sedentary women: sit less, live more!
AB  - Even lay persons know that a sedentary lifestyle is unhealthy. Still, the
      majority of people do not comply with current recommendations for physical
      activity. Data on the ill effects of sedentarism keep on increasing, clearly
      showing a significant adverse impact and increased risk for cardiovascular
      disease, cancer, fracture and various overweight-related metabolic conditions.
      The simple fact that prolonged sitting is associated with a shorter life span
      must be repeatedly discussed with our patients. 

PMID- 25868823
TI  - Coronary artery calcification is associated with high serum concentration of
      undercarboxylated osteocalcin in asymptomatic Korean men.
AB  - CONTEXT: Osteocalcin is associated with energy metabolism and atherosclerosis,
      besides bone metabolism. However, the association between osteocalcin or its
      undercarboxylated form (ucOC) and coronary artery calcification is controversial.
      OBJECTIVE: To evaluate the relationship between coronary artery calcium score
      (CACS) and the concentration of serum osteocalcin and ucOC. DESIGN: Cross
      sectional. PATIENTS: A total of 162 subjects (114 men and 48 women) with no
      angina symptom. MEASUREMENTS: Serum analyses included glucose, insulin and lipid
      profiles as well as osteocalcin and ucOC. Bone mineral density (BMD) was measured
      by dual X-ray absorptiometry. CACS was measured using multidetector computed
      tomography and categorized into CACS = 0 and CACS > 0. RESULTS: The mean
      osteocalcin concentration in men was 15.6 +/- 4.2 for CACS = 0 group and 14.1 +/-
      4.0 for CACS > 0 group, respectively (P = 0.050). In women, the osteocalcin
      concentration, ucOC concentration and ucOC to osteocalcin ratio (OCR) were not
      different between the CACS groups. However, the concentrations of osteocalcin and
      ucOC were significantly lower in women with hypertension or diabetes than those
      without, respectively. In the multivariate logistic regression models adjusted
      for medical history, body mass index, lipid profiles, insulin resistance and BMD
      in men, the higher concentration of ucOC and higher OCR showed significant
      association with coronary calcification (CACS > 0). CONCLUSION: Higher ucOC
      concentration was associated with coronary artery calcification independent of
      conventional cardiovascular risk factors and BMD in men.

PMID- 25868824
TI  - Paclitaxel induces acute pain via directly activating toll like receptor 4.
AB  - Paclitaxel, a powerful anti-neoplastic drug, often causes pathological pain,
      which significantly reduces the quality of life in patients. Paclitaxel-induced
      pain includes pain that occurs immediately after paclitaxel treatment (paclitaxel
      associated acute pain syndrome, P-APS) and pain that persists for weeks to years
      after cessation of paclitaxel treatment (paclitaxel induced chronic neuropathic
      pain). Mechanisms underlying P-APS remain unknown. In this study, we found that
      paclitaxel causes acute pain in rodents in a dose-dependent manner. The
      paclitaxel-induced acute pain occurs within 2 hrs after a single intravenous
      injection of paclitaxel. This is accompanied by low levels of paclitaxel
      penetrating into the cerebral spinal fluid and spinal dorsal horn. We
      demonstrated that an intrathecal injection of paclitaxel induces mechanical
      allodynia in a dose-dependent manner. Paclitaxel causes activation of toll like
      receptor 4 (TLR4) in the spinal dorsal horn and dorsal root ganglions. Through
      activating TLR4, paclitaxel increases glutamatergic synaptic activities and
      reduces glial glutamate transporter activities in the dorsal horn. Activations of
      TLR4 are necessary in the genesis of paclitaxel-induced acute pain. The cellular
      and molecular signaling pathways revealed in this study could provide rationales
      for the development of analgesics and management strategies for P-APS in
      patients. 

PMID- 25868825
TI  - Why it matters. A paired editorial for "Hypoglycemia after Roux-en-Y gastric
      bypass: detection rates of continuous glucose monitoring (CGM) versus mixed meal
      test".

PMID- 25868826
TI  - Influences of general self-efficacy and weight bias internalization on physical
      activity in bariatric surgery candidates.
AB  - BACKGROUND: Physical activity (PA) seems to be important for long-term weight
      loss after bariatric surgery; however, studies provide evidence for insufficient
      PA levels in bariatric patients. Research found self-efficacy to be associated
      with PA and weight bias internalization, for which an influence on mental and
      physical health has been shown in recent studies. The purpose of the present
      study was to investigate the influence of general self-efficacy on PA, mediated
      by weight bias internalization. METHODS: In 179 bariatric surgery candidates,
      general self-efficacy, weight bias internalization, and different intensities of
      PA were assessed by self-report questionnaires. Structural equation modeling was
      used to analyze the assumed mediational relationship. RESULTS: After controlling
      for sociodemographic variables, weight bias internalization fully mediated the
      association between general self-efficacy and moderate-intense as well as
      vigorous-intense PA. Lower general self-efficacy predicted greater weight bias
      internalization, which in turn predicted lower levels of moderate-intense and
      vigorous-intense PA. CONCLUSIONS: The results suggest an influence of weight bias
      internalization on preoperative PA in bariatric surgery candidates. Subsequently,
      implementation of interventions addressing weight bias internalization in the
      usual treatment of bariatric surgery candidates might enhance patients'
      preoperative PA, while longitudinal analyses are needed to further examine its
      predictive value on PA after bariatric surgery.

PMID- 25868827
TI  - Impact of gastrointestinal bypass on nonmorbidly obese type 2 diabetes mellitus
      patients after gastrectomy.
AB  - BACKGROUND: Our objective was to investigate the predictive preoperative factors
      and surgical components for type 2 diabetes mellitus (T2D) improvement in
      patients with body mass index (BMI) <35 kg/m(2). METHODS: All patients undergoing
      curative surgical resection for gastric cancer involving Billroth I
      gastroduodenal anastomosis, Billroth II gastrojejunal anastomosis (B-I, B-II), or
      Roux-en-Y total gastrectomy (RYTG), from 2008-2011, were retrospectively
      reviewed. Of these, 90 patients with T2D were analyzed. The study population was
      divided into the "improved" and "not improved" groups. The preoperative and
      postoperative data were assessed using multiple logistic regression analysis. To
      assess the necessary surgical elements, the gastrointestinal reconstruction
      methods were categorized according to the presence of the fundus and
      gastrointestinal bypass. RESULTS: Fifty-four patients (60%) experienced
      improvements in their T2D 2 years after surgery. Lower preoperative glycated
      hemoglobin (A1C) (odds ratio [OR]: .502; 95% confidence interval [CI]: .313-.804;
      P = .004), not using multiple oral antidiabetic medications (OR: .341; 95% CI:
      .120-.969; P = .043), and high BMI before surgery (OR: 1.294; 95% CI: 1.074
      1.559; P = .007) were identified as independent predictors of T2D improvements.
      RYTG was more effective at improving T2D than B-I (OR: .160; 95% CI: .032-.794; P
      = .025). Statistical analysis according to the surgical elements showed that the
      bypass procedure was associated with T2D improvements (OR: 3.023; 95% CI: .989
      9.240; P = .052). CONCLUSION: Gastrointestinal bypass significantly contributes
      to T2D improvements in patients with BMI <35 kg/m(2). Low A1C, high BMI, and not
      using multiple antidiabetic medications were important predictors of T2D
      improvement.

PMID- 25868828
TI  - Should metabolic surgery be offered in morbidly obese patients with type I
      diabetes?
AB  - BACKGROUND: Bariatric surgery has recently been endorsed as an effective
      treatment of type 2 diabetes (T2D) in severely obese patients. Little is known
      about its metabolic effects in type 1 diabetes (T1D). The objectives were to
      assess bariatric surgery outcomes in T1D obese patients who underwent either a
      biliopancreatic diversion (BPD) or a sleeve gastrectomy (SG) and who were matched
      with T2D obese patients requiring insulin therapy. The study setting was at a
      university-affiliated tertiary care center. METHODS: Through retrospective
      analysis of prospectively collected data, ten patients with T1D (7 BPD, 3 SG)
      were matched with 20 patients with T2D (14 BPD, 6 SG) according to age, gender,
      type of surgery, initial Body Mass Index and insulin requirements (1:2 matching).
      Weight loss, diabetes control, and remission of co-morbidities were compared.
      RESULTS: Mean follow-up was 55.1 months. Mean Excess BMI Loss% tended to be
      greater in T1D patients compared to T2D (77.1% versus 68.3%, P = .14). The
      remission and improvement rates of T2D were 55% and 45% versus 0% and 90% for
      T1D. The remission rate of T2D was significantly greater after BPD (71.43%)
      compared to SG (16.67%, P = .04). Insulin requirements were significantly reduced
      in both groups after surgery (T1D: .44 +/-.24 versus 1.09 +/-.7 units/kg/d, P =
      0.03, T2D: .03 +/-.12 versus .89 +/-.77 units/kg/d, P = .0001). Remission rates
      of hypertension and dyslipidemia were similar for T1D and T2D (66.7% versus
      62.5%, P = .63 and 88.9% versus 75%, P = .23). CONCLUSIONS: Even if metabolic
      surgery has limited effect on glycemic control in T1D, it improves insulin
      sensitivity and other co-morbidities. It should be considered as a therapeutic
      option in selected obese patients with metabolic syndrome and high cardio
      vascular risk.

PMID- 25868830
TI  - Presidential address given before the Annual Meeting of the American Society for
      Bariatric Surgery, June, 1989, Nashville, TN.

PMID- 25868829
TI  - The REDUCE pivotal trial: a prospective, randomized controlled pivotal trial of a
      dual intragastric balloon for the treatment of obesity.
AB  - BACKGROUND: Saline-filled intragastric balloon devices are reversible endoscopic
      devices designed to occupy stomach volume and reduce food intake. OBJECTIVE: To
      evaluate the safety and effectiveness of a dual balloon system plus diet and
      exercise in the treatment of obesity compared to diet and exercise alone.
      SETTING: Academic and community practice, United States. METHODS: Participants (n
      = 326) with body mass index (BMI) 30-40 kg/m(2) were randomized to endoscopic DBS
      treatment plus diet and exercise (DUO, n = 187) or sham endoscopy plus diet and
      exercise alone (DIET, n = 139). Co-primary endpoints were a between-group
      comparison of percent excess weight loss (%EWL) and DUO subject responder rate,
      both at 24 weeks. Thereafter DUO patients had the DBS retrieved followed by 24
      additional weeks of counseling; DIET patients were offered DBS treatment.
      RESULTS: Mean BMI was 35.4. Both primary endpoints were met. DUO weight loss was
      over twice that of DIET. DUO patients had significantly greater %EWL at 24 weeks
      (25.1% intent-to-treat (ITT), 27.9% completed cases (CC, n = 167) compared with
      DIET patients (11.3% ITT, P = .004, 12.3% CC, n = 126). DUO patients
      significantly exceeded a 35% response rate (49.1% ITT, P<.001, 54.5% CC) for
      weight loss dichotomized at 25%EWL. Accommodative symptoms abated rapidly with
      support and medication. Balloon deflation occurred in 6% without migrations.
      Early retrieval for nonulcer intolerance occurred in 9%. Gastric ulcers were
      observed; a minor device change led to significantly reduced ulcer size and
      frequency (10%). CONCLUSION: The DBS was significantly more effective than diet
      and exercise in causing weight loss with a low adverse event profile.

PMID- 25868831
TI  - Bariatric surgery in patients with reduced kidney function: an analysis of short
      term outcomes.
AB  - BACKGROUND: With rates of obesity among patients with chronic kidney disease
      (CKD) mirroring that of the general population, there is growing interest in
      offering bariatric surgery to these patients. We sought to determine the safety
      of bariatric surgery in this patient population. METHODS: Patients who underwent
      selected laparoscopic bariatric procedures between 2005 and 2011. Estimated
      glomerular filtration rate (eGFR) was calculated and divided into stages of CKD.
      Procedures included Roux-en-Y gastric bypass (RYGB), laparoscopic adjustable
      gastric band (LAGB), and laparoscopic sleeve gastrectomy (SG). Univariable
      analysis and multivariable adjustment was used to compare complication rates
      across stages of eGFR. RESULTS: A total of 64,589 patients were included: 64.5%
      underwent RYGB, 29.8% LAGB, and 5.7% SG. A total of 61.7% of patients had normal
      eGFR (Stage 1), 32.0% were stage 2, 5.3% were stage 3, and 1.0% were stage 4/5.
      After adjusting for relevant patient characteristics, there was a trend toward
      increasing complications from stage 1 to stage 4/5 CKD among RYGB, LAGB, and SG
      groups, but none were statistically significant. Similarly, major complications
      generally increased across stages of CKD for each procedure, but was only
      significant for RYGB comparing stage 3 to stage 1 (OR 1.22; 95% CI: 1.01-1.47; P
      = .042) and risk difference .96% (95% CI: .03-1.96). Considering only stage 4/5
      CKD, overall (P = .114) and major complications (P = .032) were highest in the
      RYGB group, followed by SG and LAGB. CONCLUSION: More advanced stages of CKD do
      not appear to be statistically associated with an increased risk of 30-day
      postoperative complications.

PMID- 25868832
TI  - Sexual functioning and sex hormones in men who underwent bariatric surgery.
AB  - BACKGROUND: The relationship between obesity and impairments in male sexual
      functioning is well documented. Relatively few studies have investigated changes
      in sexual functioning and sex hormones in men who achieve significant weight loss
      with bariatric surgery. The objective of this study was to assess changes in
      sexual functioning, sex hormones, and relevant psychosocial constructs in men who
      underwent bariatric surgery. METHODS: A prospective cohort study of 32 men from
      the Longitudinal Assessment of Bariatric Surgery-2 (LABS) investigation who
      underwent a Roux-en-Y gastric bypass (median body mass index [25th percentile,
      75th percentile] 45.1 [42.0, 52.2]) and completed assessments between 2006 and
      2012. Bariatric surgery was performed by a LABS-certified surgeon. Sexual
      functioning was assessed by the International Index of Erectile Functioning
      (IIEF). Hormones were assessed by blood assay. Quality of life (QoL), body image,
      depressive symptoms and marital adjustment were assessed by questionnaire.
      RESULTS: Men lost, on average, (95% confidence interval) 33.3% (36.1%, 30.5%) of
      initial weight at postoperative year 1, 33.6% (36.8%, 30.5%) at year 2, 31.0%
      (34.1%, 27.9%) at year 3, and 29.4% (32.7%, 26.2%) at year 4. Participants
      experienced significant increases in total testosterone (P<.001) and sex hormone
      binding globulin (SHBG) (P<.001) through postoperative year 4. Although men
      reported improvements in sexual functioning after surgery, these changes did not
      significantly differ from baseline, with the exception of overall satisfaction at
      postoperative year 3 (P = .008). Participants reported significant improvements
      in physical domains of health-related quality of life (HRQoL), all domains of
      weight-related QOL, and body image, but not in the mental health domains of HRQoL
      or relationship satisfaction. CONCLUSIONS: Men who lost approximately one third
      of their weight after Roux-en-Y gastric bypass experienced significant increases
      in total testosterone and SHBG. They did not, however, report significant
      improvements in sexual functioning, relationship satisfaction, or mental health
      domains of HRQoL. This pattern of results differs from that of women who have
      undergone bariatric surgery, who reported almost uniform improvements in sexual
      functioning and psychosocial status.

PMID- 25868833
TI  - Congestive heart failure is a risk factor for venous thromboembolism in bariatric
      surgery.
AB  - BACKGROUND: Venous thromboembolism (VTE) is a major complication of bariatric
      surgery leading to significant morbidity and mortality. We sought to identify
      predictive factors that increase the risk of deep venous thrombosis (DVT) and
      pulmonary embolism (PE) using data from the National Surgical Quality Improvement
      Program (NSQIP). METHODS: Patients undergoing bariatric procedures from 2005-2012
      were identified in the NSQIP database. Pretreatment patient characteristics were
      examined by laparoscopic and open treatment groups using t tests and chi-square
      regression. Independent associations between patient characteristics and DVT and
      PE were examined using logistic regression. Logistic regression was also used to
      examine whether patients who had postprocedure DVT or PE were more likely than
      those who did not have these events to have additional morbidity and mortality
      outcomes. RESULTS: 102,869 patients underwent bariatric surgery (96,085
      laparoscopic; 6,784 open) from 2005-2012. Preoperative variables associated with
      increased risk of DVT in laparoscopic bariatric surgery are male gender, higher
      BMI, congestive heart failure (CHF), and hypertension (HTN). Preoperative
      variables associated with increased risk of PE in laparoscopic bariatric surgery
      are male gender, age greater than or equal to 60, higher BMI, African American
      race, chronic obstructive pulmonary disease (COPD) and CHF. There are no
      preoperative variables associated with an increased risk of DVT in open bariatric
      surgery although there is a trend toward significance with CHF. Finally, higher
      BMI and CHF is associated with an increased risk of PE in open bariatric surgery.
      CONCLUSIONS: CHF is a significant risk factor for VTE in bariatric surgery.
      Surgeons should consider aggressive screening and VTE prophylaxis in patients
      with CHF and other known risk factors to decrease postoperative morbidity from
      VTE.

PMID- 25868834
TI  - Gastrojejunostomy technique and anastomotic complications in laparoscopic gastric
      bypass.
AB  - BACKGROUND: Various surgical techniques exist to create the gastrojejunostomy
      during laparoscopic Roux-en-Y gastric bypasses (LRYGB). A hand-sewn anastomosis
      (HSA) and circular-stapled anastomosis (CSA) are both common techniques. We
      hypothesized that the CSA was associated with a greater incidence of anastomotic
      complications. As a secondary aim, we sought to determine if weight loss varied
      by technique. METHODS: This study is a retrospective review of patients who
      underwent primary LRYGB at the Medical College of Wisconsin from January 2010 to
      December 2011. Procedures were performed by one of 2 surgeons, each with a
      preferred gastrojejunostomy technique. Clinical information and patient outcomes
      were followed up to one year. RESULTS: A total of 190 patients underwent LRYGB
      during the study interval. The majority of patients underwent HSA. Forty-one of
      190 (21.6%) patients experienced one or more complications. Most complications
      were Clavien Classification Grade III and were experienced within 30 days of
      surgery in 3 (2.2%) HSA patients and 6 (10.9%) CSA patients (P = .02).
      Anastomotic complications occurred more frequently with the CSA technique
      (marginal ulcer 5.5% CSA versus .7% HSA; P = .04 and stenosis 16.4% CSA versus 3%
      HSA; P = .01). There were no gastrojejunostomy leaks in this series. Operative
      time was significantly longer in HSA patients (204 minutes HSA versus 166 minutes
      CSA; P<.01), but length of hospital stay did not differ. Weight loss at 12 months
      was similar between techniques (69.4% percent excess BMI lost (EBMIL) HSA versus
      76.6% EBMIL CSA; P = .11). No patients were lost to follow-up at 30 days. Thirty
      five patients (19%) were lost to follow-up by one year. CONCLUSION: The CSA
      technique of gastrojejunostomy in gastric bypass is associated with a higher rate
      of nonlife threatening anastomotic complications than the HSA technique.
      Operative times are significantly longer for HSA, but length of hospital stay
      (LOS) and long-term weight loss are equivalent.

PMID- 25868835
TI  - Surgical management and outcomes of patients with marginal ulcer after Roux-en-Y
      gastric bypass.
AB  - BACKGROUND: Marginal ulcers (MUs) are potentially complex complications after
      Roux-en-Y gastric bypass. Although most resolve with medical management, some
      require surgical intervention. Many surgical options exist, but there is no
      standardized approach, and few reports of outcomes have been documented in the
      literature. The objective of this study was to determine the outcomes of surgical
      management of marginal ulcers. METHODS: Data from all patients who underwent
      surgical intervention between 2004 and 2012 for treatment of MU after previous
      Roux-en-Y gastric bypass were reviewed. RESULTS: Twelve patients with MUs
      underwent reoperation. Nine patients had associated gastrogastric fistulae (75%).
      The median time to reoperation was 43 months. Ten patients underwent subtotal
      gastrectomy, of which 9 had a revision of the gastrojejunal anastomosis and 1 did
      not. One underwent total gastrectomy with esophagojejunal anastomosis for ulcer
      after previous revisional partial gastrectomy, and 1 patient underwent video
      assisted thoracoscopic truncal vagotomy for persistent ulcer-related bleeding in
      the early postoperative period. Three patients (25%) experienced postoperative
      complications associated with revisional surgery requiring reoperation. At median
      follow-up time of 35 months, 7 patients (58%) had chronic abdominal pain, and 4
      patients (33%) had intermittent diarrhea. Three patients (25%) were lost to
      recent follow-up. None had recurrence of MU. CONCLUSION: Patients can undergo one
      of several available surgical interventions, including laparoscopic subtotal
      gastrectomy with gastrojejunostomy revision. Though this appears to offer
      definitive treatment of MU, its benefits must be weighed against the increased
      risk of significant postoperative complications and chronic symptoms related to
      revisional surgery.

PMID- 25868836
TI  - Laparoscopic sleeve gastrectomy for type 2 diabetes mellitus: predicting the
      success by ABCD score.
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is becoming a primary bariatric
      surgery for obesity and related diseases. This study presents the outcome of LSG
      with regard to the remission of type 2 diabetes mellitus (T2 DM) and the
      usefulness of a grading system to categorize and predict outcome of T2 DM
      remission. METHODS: A total of 157 patients with T2 DM (82 women and 75 men) with
      morbid obesity (mean body mass index 39.0+/-7.4 kg/m(2)) who underwent LSG from
      2006 to 2013 were selected for the present study. The ABCD score is composed of
      the patient's age, body mass index, C-peptide level, and duration of T2 DM (yr).
      The remission of T2 DM after LSG was evaluated using the ABCD score. RESULTS: At
      12 months after surgery, 85 of the patients had complete follow-up data. The
      weight loss was 26.5% and the mean HbA1c decreased from 8.1% to 6.1%. A
      significant number of patients had improvement in their glycemic control,
      including 45 (52.9%) patients who had complete remission (HbA1c<6.0%), another 18
      (21.2%) who had partial remission (HbA1c<6.5%), and 9 (10.6%) who improved
      (HbA1c<7%). Patients who had T2 DM remission after surgery had a higher ABCD
      score than those who did not (7.3+/-1.7 versus 5.2+/-2.1, P<.05). Patients with a
      higher ABCD score were also at a higher rate of success in T2 DM remission (from
      0% in score 0 to 100% in score 10). CONCLUSION: LSG is an effective and well
      tolerated procedure for achieving weight loss and T2 DM remission. The ABCD
      score, a simple multidimensional grading system, can predict the success of T2 DM
      treatment by LSG.

PMID- 25868837
TI  - Predicting potentially preventable hospital readmissions following bariatric
      surgery.
AB  - BACKGROUND: Using hospital readmissions as a quality of care measure predicates
      that some readmissions were preventable. OBJECTIVES: This study identifies
      predictors of potentially preventable readmissions (PPR) within 30 days of
      bariatric surgery discharge. SETTING: New York State acute care hospitals.
      METHODS: Adult inpatient surgical discharges, during 2012, with a principal
      diagnosis of overweight or obesity and a principal procedure for bariatric
      surgery were identified. Logistic regression was used to evaluate surgical
      approach, sex, age, race/ethnicity, payor, body mass index, complications and co
      morbidities recorded during the surgical admission. RESULTS: There were 10,448
      surgeries studied for readmission of which 552 were followed by a PPR, for a
      statewide rate of 5.3 per 100 surgeries. Laparoscopic Roux-en-Y Gastric Bypass
      (LRYGB) was the most common surgical approach (46.0%), then Sleeve Gastrectomy
      (SG) (41.3%), Laparoscopic Adjustable Gastric Band (LAGB) (8.1%), and Open Roux
      en-Y Gastric Bypass (RYGB) (4.6%). RYGB had the highest PPR rate (8.8), followed
      by LRYGB (6.1), SG (4.3) and LAGB (3.3). Compared to LAGB, the odds of a PPR in
      patients with RYGB, LRYGB, and SG increased by 2.4 fold, 1.8 fold and 1.2 fold
      respectively. Black, non-Hispanic patients were at a greater risk of PPR (odds
      ratio 2.0, P<.0001) compared to White, non-Hispanic patients while the risk of a
      PPR increased by 2-fold in patients with a surgical complication. CONCLUSIONS:
      Taking all patient risk factors into account, the most significant predictors of
      a PPR were surgical approach, race and the presence of a surgical complication.

PMID- 25868838
TI  - Predictors of metabolic syndrome persistence 1 year after laparoscopic Roux-en-Y
      gastric bypass.
AB  - BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (LRYGB) is effective in
      reversing the metabolic syndrome (MS) in up to 90% of patients. OBJECTIVES: The
      aim of this study was to determine predictors of MS persistence 1 year after
      LRYGB. SETTING: University Hospital, France. METHODS: Ninety-one patients with a
      mean age of 44.4 years and a mean body mass index (BMI) of 43.1 kg/m2 meeting the
      criteria for MS were enrolled in this prospective study. Anthropometric,
      metabolic, and inflammatory biological parameters were assessed before and 1 year
      after LRYGB. Patients were divided into 2 groups according to the persistence (MS
      nonresponders) or resolution of MS (MS responders) 1 year after LRYGB and a
      comparison was performed at baseline and 1 year after surgery. RESULTS: Sixty
      nine patients (75.8%) underwent remission, while 22 (24.2%) showed persistence of
      MS 1 year after LRYGB. At baseline the MS nonresponders group presented
      significantly higher values of fasting plasma glucose (7.8 versus 5.3 mmol/L, P =
      .004), glycosylated hemoglobin (HbA1c, 7.3% versus 5.9%, P = .0004),
      triglycerides (TG, 2.37 versus 1.33 mmol/L, P = .006), and homeostasis model
      assessment of insulin resistance (HOMA-IR, 442.5 versus 256, P = .006). The rate
      of diabetes was significantly higher in this group (68.2% versus 36.8%, P =
      .0086), as well as the number of MS components per patient. One year after LRYGB,
      the MS nonresponders showed a significantly lower excess BMI lost (EBMIL) (56.1%
      versus 82.4%, P = .00008). On multivariate analysis, baseline levels of TG,
      glucose metabolism markers and EBMIL were associated with the persistence of MS.
      CONCLUSION: Baseline levels of TG, plasma fasting glucose, and HbA1c, as well as
      history of type 2 diabetes and EBMIL, represent predictors of MS persistence 1
      year after LRYGB.

PMID- 25868839
TI  - An insight on the superior outcome of sleeve gastrectomy over gastric plication.

PMID- 25868840
TI  - Vertical sleeve gastrectomy specimens have a high prevalence of unexpected
      histopathologic findings requiring additional clinical management.
AB  - BACKGROUND: Laparoscopic vertical sleeve gastrectomy is used with increasing
      frequency as a therapeutic option for morbid obesity. Before the procedure,
      patients undergo a rigorous preoperative evaluation including double contrast
      upper gastrointestinal radiographic series at our institution. Patients
      undergoing sleeve gastrectomy are presumed to have no significant gastric
      pathology. OBJECTIVES: To investigate the prevalence of histopathologic findings
      requiring clinical follow-up in sleeve gastrectomy specimens. SETTING: University
      Hospital, United States. METHODS: Retrospective review was conducted of all
      primary vertical sleeve gastrectomy specimens performed for morbid obesity at our
      institution from July 2008 until August 2012 (N = 248). RESULTS: Unanticipated
      findings warranting clinical follow-up were identified in 8.4% of cases and
      included cases of H. pylori gastritis, autoimmune gastritis with microcarcinoid
      formation, necrotizing vasculitis, and intestinal metaplasia. H. pylori was
      identified in 5.2% of all cases and in 33.3% of cases of gastritis. Neoplasms
      were identified at laparoscopy in 2 additional cases (0.8%). CONCLUSIONS:
      Surgeons and pathologists should be aware of the high prevalence of diagnoses
      requiring clinical follow-up in vertical sleeve gastrectomy specimens.

PMID- 25868841
TI  - Subclinical hypothyroidism and its relation to obesity in patients before and
      after Roux-en-Y gastric bypass.
AB  - BACKGROUND: Subclinical hypothyroidism (SH), defined as a raised serum thyroid
      stimulating hormone (TSH) with a normal free thyroxine (FT4), is occasionally
      observed in morbidly obese patients. OBJECTIVES: It is currently not known
      whether thyroid hormone treatment is indicated. The aim of the present study was
      to assess the changes in thyroid hormone levels in thyroxine-naive patients with
      SH in response to weight loss induced by Roux-en-Y gastric bypass (RYGB).
      SETTING: General hospital specialized in bariatric surgery. METHODS: Serum levels
      of TSH and FT4 were measured at baseline in 503 patients presenting for RYGB. In
      patients diagnosed with SH, these measurements were repeated 12 months
      postoperatively. RESULTS: SH de novo was present in 71 out of 503 patients
      (14.1%). One-year follow-up was available in 61 out of 71 patients (86%). TSH
      level >10 mU/L was observed in 3 patients (.5%). RYGB induced a decrease in BMI
      from 47+/-8 kg/m(2) to 33+/-6 kg/m(2) at 12-month follow-up (P<.001), and this
      was associated with a decrease in TSH from 5.8+/-2.0 to 2.8+/-1.3 mU/L (P<.001)
      and a decrease in FT4 from 15.2+/-2.1 to 13.9+/-2.3 pmol/L (P<.001),
      respectively. SH completely resolved in 53 (87%) of the de novo cases.
      CONCLUSION: The prevalence of SH de novo is high in morbidly obese patients.
      After RYGB it resolves in about 90% of patients. This high degree of spontaneous
      recovery suggests that follow-up alone is sufficient in the majority of patients.

PMID- 25868842
TI  - Bronchial epithelial cells: The key effector cells in the pathogenesis of chronic
      obstructive pulmonary disease?
AB  - The primary function of the bronchial epithelium is to act as a defensive barrier
      aiding the maintenance of normal airway function. Bronchial epithelial cells
      (BEC) form the interface between the external environment and the internal
      milieu, making it a major target of inhaled insults. However, BEC can also serve
      as effectors to initiate and orchestrate immune and inflammatory responses by
      releasing chemokines and cytokines, which recruit and activate inflammatory
      cells. They also produce excess reactive oxygen species as a result of an
      oxidant/antioxidant imbalance that contributes to chronic pulmonary inflammation
      and lung tissue damage. Accumulated mucus from hyperplastic BEC obstructs the
      lumen of small airways, whereas impaired cell repair, squamous metaplasia and
      increased extracellular matrix deposition underlying the epithelium is associated
      with airway remodelling particularly fibrosis and thickening of the airway wall.
      These alterations in small airway structure lead to airflow limitation, which is
      critical in the clinical diagnosis of chronic obstructive pulmonary disease
      (COPD). In this review, we discuss the abnormal function of BEC within a
      disturbed immune homeostatic environment consisting of ongoing inflammation,
      oxidative stress and small airway obstruction. We provide an overview of recent
      insights into the function of the bronchial epithelium in the pathogenesis of
      COPD and how this may provide novel therapeutic approaches for a number of
      chronic lung diseases. 

PMID- 25868845
TI  - Increased DNA methylation of scavenger receptor class B type I contributes to
      inhibitory effects of prenatal caffeine ingestion on cholesterol uptake and
      steroidogenesis in fetal adrenals.
AB  - Steroid hormones synthesized from cholesterol in the fetal adrenal are crucial
      for fetal development. We have observed the inhibited fetal adrenal
      corticosterone synthesis and increased intrauterine growth retardation (IUGR)
      rate in rats under prenatal caffeine ingestion. The aim of this study is to
      evaluate the effects of prenatal caffeine ingestion on cholesterol supply in
      fetal adrenal steroidogenesis in rats and explore the underlying epigenetic
      mechanisms. Pregnant Wistar rats were treated with 60 mg/kg . d caffeine from
      gestational day (GD) 7 to GD17. Histological changes of fetal adrenals and
      increased IUGR rates were observed in the caffeine group. There were
      significantly decreased steroid hormone contents and cholesterol supply in
      caffeine-treated fetal adrenals. Data from the gene expression array suggested
      that prenatal caffeine ingestion caused increased expression of genes related to
      DNA methylation and decreased expression of genes related to cholesterol uptake.
      The following conjoint analysis of DNA methylation array with these
      differentially expressed genes suggested that scavenger receptor class B type I
      (SR-BI) may play an important role in caffeine-induced cholesterol supply
      deficiency. Moreover, real-time RT-PCR and immunohistochemical detection
      certified the inhibitory effects of caffeine on both mRNA expression and protein
      expression of SR-BI in the fetal adrenal. And the increased DNA methylation
      frequency in the proximal promoter of SR-BI was confirmed by bisulfite-sequencing
      PCR. In conclusion, prenatal caffeine ingestion can induce DNA hypermethylation
      of the SR-BI promoter in the rat fetal adrenal. These effects may lead to
      decreased SR-BI expression and cholesterol uptake, which inhibits steroidogenesis
      in the fetal adrenal.

PMID- 25868843
TI  - Glutathione S-transferase P protects against cyclophosphamide-induced
      cardiotoxicity in mice.
AB  - High-dose chemotherapy regimens using cyclophosphamide (CY) are frequently
      associated with cardiotoxicity that could lead to myocyte damage and congestive
      heart failure. However, the mechanisms regulating the cardiotoxic effects of CY
      remain unclear. Because CY is converted to an unsaturated aldehyde acrolein, a
      toxic, reactive CY metabolite that induces extensive protein modification and
      myocardial injury, we examined the role of glutathione S-transferase P (GSTP), an
      acrolein-metabolizing enzyme, in CY cardiotoxicity in wild-type (WT) and GSTP
      null mice. Treatment with CY (100-300 mg/kg) increased plasma levels of creatine
      kinase-MB isoform (CK . MB) and heart-to-body weight ratio to a significantly
      greater extent in GSTP-null than WT mice. In addition to modest yet significant
      echocardiographic changes following acute CY-treatment, GSTP insufficiency was
      associated with greater phosphorylation of c-Jun and p38 as well as greater
      accumulation of albumin and protein-acrolein adducts in the heart. Mass
      spectrometric analysis revealed likely prominent modification of albumin,
      kallikrein-1-related peptidase, myoglobin and transgelin-2 by acrolein in the
      hearts of CY-treated mice. Treatment with acrolein (low dose, 1-5 mg/kg) also led
      to increased heart-to-body weight ratio and myocardial contractility changes.
      Acrolein induced similar hypotension in GSTP-null and WT mice. GSTP-null mice
      also were more susceptible than WT mice to mortality associated with high-dose
      acrolein (10-20 mg/kg). Collectively, these results suggest that CY
      cardiotoxicity is regulated, in part, by GSTP, which prevents CY toxicity by
      detoxifying acrolein. Thus, humans with low cardiac GSTP levels or polymorphic
      forms of GSTP with low acrolein-metabolizing capacity may be more sensitive to CY
      toxicity.

PMID- 25868844
TI  - Toxicological significance of renal Bcrp: Another potential transporter in the
      elimination of mercuric ions from proximal tubular cells.
AB  - Secretion of inorganic mercury (Hg(2+)) from proximal tubular cells into the
      tubular lumen has been shown to involve the multidrug resistance-associated
      protein 2 (Mrp2). Considering similarities in localization and substrate
      specificity between Mrp2 and the breast cancer resistance protein (Bcrp), we
      hypothesize that Bcrp may also play a role in the proximal tubular secretion of
      mercuric species. In order to test this hypothesis, the uptake of Hg(2+) was
      examined initially using inside-out membrane vesicles containing Bcrp. The
      results of these studies suggest that Bcrp may be capable of transporting certain
      conjugates of Hg(2+). To further characterize the role of Bcrp in the handling of
      mercuric ions and in the induction of Hg(2+)-induced nephropathy, Sprague-Dawley
      and Bcrp knockout (bcrp(-/-)) rats were exposed intravenously to a non
      nephrotoxic (0.5 MUmol . kg(-1)), a moderately nephrotoxic (1.5 MUmol . kg(-1))
      or a significantly nephrotoxic (2.0 MUmol . kg(-1)) dose of HgCl2. In general,
      the accumulation of Hg(2+) was greater in organs of bcrp(-/-) rats than in
      Sprague-Dawley rats, suggesting that Bcrp may play a role in the export of Hg(2+)
      from target cells. Within the kidney, cellular injury and necrosis was more
      severe in bcrp(-/-) rats than in controls. The pattern of necrosis, which was
      localized in the inner cortex and the outer stripe of the outer medulla, was
      significantly different from that observed in Mrp2-deficient animals. These
      findings suggest that Bcrp may be involved in the cellular export of select
      mercuric species and that its role in this export may differ from that of Mrp2.

PMID- 25868846
TI  - Cross-resistance between fipronil and lindane in Rhipicephalus (Boophilus)
      microplus.
AB  - The southern cattle tick, Rhipicephalus (Boophilus) microplus (Canestrini), is
      one of the most damaging parasites of cattle in tropical and subtropical regions.
      Several chemical groups have been used for its control, including cyclodienes
      (lindane and dieldrin). In Uruguay and Brazil these products were used at the
      beginning of the 1960s and during a few years. Fipronil and lindane act on the
      same target site. In both countries, southern cattle tick resistance to fipronil
      has sometimes developed quickly after only a few acaricide treatments (three to
      seven). The objective of the present study was to determine cross-resistance
      between fipronil and lindane in southern cattle ticks from Uruguay and Brazil.
      Initially, the FAO's (Food and Agricultural Organization) larval packet test with
      lindane was applied to a fipronil-resistant strain and to susceptible field
      populations. Mozo and POA strains were used as the susceptible controls. A larval
      immersion test was used to assess fipronil toxicity. Of fifteen fipronil
      resistant field populations that were tested with lindane, eleven were lindane
      resistant and three were susceptible. The last three populations had incipient
      resistance to fipronil. Finally, cross-resistance between fipronil and lindane in
      the southern cattle tick is reported in this study for the first time. 

PMID- 25868847
TI  - An evidence-based approach to the evaluation of ethnoveterinary medicines against
      strongyle nematodes of equids.
AB  - Cyathostomins are the most important gastrointestinal nematode infecting equids.
      Their effective control is currently under threat due to widespread resistance to
      the broad spectrum anthelmintics licenced for use in equids. In response to
      similar resistance issues in other helminths, there has been increasing interest
      in alternative control strategies, such as bioactive plant compounds derived from
      traditional ethnoveterinary treatments. This study used an evidence-based
      approach to evaluate the potential use of plant extracts from the UK and Ethiopia
      to treat cyathostomins. Plants were shortlisted based on findings from a
      literature review and additionally, in Ethiopia, the results of a participatory
      rural appraisal (PRA) in the Oromia region of the country. Systematic selection
      criteria were applied to both groups to identify five Ethiopian and four UK
      plants for in vitro screening. These included Acacia nilotica (L.) Delile,
      Cucumis prophetarum L., Rumex abyssinicus Jacq., Vernonia amygdalina Delile. and
      Withania somnifera (L.) Dunal from Ethiopia and Allium sativum L. (garlic),
      Artemisia absinthium L., Chenopodium album L. and Zingiber officinale Roscoe.
      (ginger) from the UK. Plant material was collected, dried and milled prior to
      hydro-alcoholic extraction. Crude extracts were dissolved in distilled water
      (dH2O) and dimethyl sulfoxide (DMSO), serially diluted and screened for
      anthelmintic activity in the larval migration inhibition test (LMIT) and the egg
      hatch test (EHT). Repeated measures ANOVA was used to identify extracts that had
      a significant effect on larval migration and/or egg hatch, compared to non
      treated controls. The median effective concentration (EC-50) for each extract was
      calculated using PROBIT analysis. Of the Ethiopian extracts A. nilotica, R.
      abyssinicus and C. prophetarum showed significant anthelmintic activity. Their
      lowest EC-50 values were 0.18 (confidence interval (CI): 0.1-0.3), 1.1 (CI 0.2
      2.2) and 1.1 (CI 0.9-1.4)mg/ml, respectively. All four UK extracts, A. sativum,
      C. album, Z. officinale and A. absinthium, showed significant anthelmintic
      activity. Their lowest EC-50 values were 1.1 (CI 0.9-1.3), 2.3 (CI 1.9-2.7) and
      0.3 (CI 0.2-0.4)mg/ml, respectively. Extract of A. absinthium had a relatively
      low efficacy and the data did not accurately fit a PROBIT model for the dose
      response relationship, thus an EC-50 value was not calculated. Differences in
      efficacy for each extract were noted, dependent on the assay and solvent used,
      highlighting the need for a systematic approach to the evaluation of bioactive
      plant compounds. This study has identified bioactive plant extracts from the UK
      and Ethiopia which have potential as anthelmintic forages or feed supplements in
      equids. 

PMID- 25868848
TI  - Molecular detection of the avian malaria parasite Plasmodium gallinaceum in
      Thailand.
AB  - Avian malaria is one of the most common veterinary problems in Southeast Asia.
      The standard molecular method for detection of the avian malaria parasite
      involves the phenol-chloroform extraction of parasite genomic (g)DNA followed by
      the amplification of parasite gDNA using polymerase chain reaction (PCR).
      However, the phenol-chloroform extraction method is time-consuming and requires
      large amounts of samples and toxic organic solvents, thereby limiting its
      applications for parasite detection in the field. This study aimed to compare the
      performance of chelex-100 resin and phenol/chloroform extraction methods for the
      extraction of Plasmodium gallinaceum gDNA from whole avian blood that had been
      dried on filter papers (a common field sampling method). The specificity and
      sensitivity of PCR assays for P. gallinaceum cytochrome B (cytb) and cytochrome
      oxidase subunit I (coxI) gene fragments (544 and 588bp, respectively) were
      determined, and found to be more sensitive with gDNA extracted by the chelex-100
      resin method than with the phenol/chloroform method. These PCR assays were also
      performed to detect P. gallinaceum in 29 blood samples dried on filter papers
      from domestic chickens in a malaria endemic area, where the reliable
      identification of seven field isolates of P. gallinaceum was obtained with an
      accuracy of 100%. The analysis of cytb and coxI gene nucleotide sequences
      revealed the existence of at least two genetically distinct populations of P.
      gallinaceum in Thailand, both of which differed from the reference strain 8A of
      P. gallinaceum. In conclusion, the chelex-100 resin extraction method is a simple
      and sensitive method for isolating gDNA from whole avian blood dried on filter
      paper. Genomic DNA extracted by the chelex method could subsequently be applied
      for the PCR-based detection of P. gallinaceum and DNA sequencing. Our PCR assays
      provide a reliable diagnostic tool for molecular epidemiological studies of P.
      gallinaceum infections in domestic chickens and wild birds. 

PMID- 25868849
TI  - Sarcocystis cruzi infection in wood bison (Bison bison athabascae).
AB  - Endangered wood bison (Bison bison athabascae) is the largest terrestrial mammal
      in the American continent. Animal health is an important issue in their
      conservation, and Sarcocystis cruzi may be a cause of clinical disease in
      Bovidae. Hearts of eight wood bison from Alaska, USA were examined for sarcocysts
      by histology, transmission electron microscopy, pepsin digestion, and
      molecularly. Sarcocystis bradyzoites were found in pepsin digests of all eight
      and sarcocysts were found in histologic sections of myocardium of four bison.
      Sarcocysts were thin-walled and ultrastructurally consistent with S. cruzi.
      Characterization of DNA obtained from lysis of pepsin liberated bradyzoites by
      PCR-RFLP and subsequent phylogenetic analyses matched with that previously
      reported for S. cruzi infecting cattle in the USA. Collectively, data indicate
      that wood bison is a natural intermediate host for S. cruzi. 

PMID- 25868850
TI  - Epidemiological survey on Cryptosporidium in an Equine Perinatology Unit.
AB  - The present study aims to evaluate the prevalence, pattern of spread and risk
      factors for the transmission of cryptosporidiosis in foals and mares hospitalized
      in a University Equine Perinatology Unit, where a new subtype family of
      Cryptosporidium horse genotype was described by Caffara et al. (2013). Mares (36)
      and foals (37) hospitalized during the 2012 foaling season were included.
      Multiple sampling from each animal was performed (a total of 305 stool samples
      were collected). One hundred and eleven environmental samples (gauze swabs) were
      also collected before and after the breeding season. Fourteen foals were found
      positive for Cryptosporidium spp. by PCR in at least one sample; a total of 35
      foal stool specimens were confirmed for the presence of the protozoa. Instead
      none of the stool specimens from mares were found positive. PCR-RFLP analysis
      shows Cryptosporidium parvum in 5 stool samples and Cryptosporidium horse
      genotype in 21. In 9 specimens, from 4 different foals, the profile was
      suggestive for a mixed infection. The subtyping at gp60 locus showed 2 strains as
      members of the subtype family IId and six of the subfamily IIa of C. parvum.
      Twenty isolates were identified as Cryptosporidium horse genotype subtype
      VIaA15G4. Five gauze swabs collected from the walls of the boxes where the
      animals were hosted out of 111 environmental samples examined were PCR positive
      for Cryptosporidium spp. Cryptosporidium parvum was detected in one sample
      collected before the foaling season, while Cryptosporidium horse genotype profile
      was observed in 4 wall samples collected at the end of the 2012 foaling season.
      The prevalence observed in foals (37.8%) was higher than that reported in other
      studies. These features and the diffusion of the same genotype point out as the
      EPU, where critically ill foals are hospitalized, can support the spread of
      cryptosporidiosis. Therefore, the manual tasks and the activities carried out in
      these facilities are of great importance, as they might favor the diffusion of
      the infection. 

PMID- 25868851
TI  - Associations between pre-S deletion mutation of hepatitis B virus and risk of
      hepatocellular carcinoma in the Asian population: a meta-analysis.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is the most common liver cancer,
      leading to many cancer-related deaths worldwide. Several studies have shown an
      association between pre-S deletion mutation of hepatitis B virus (HBV) and HCC
      risk, but the results remain conflicting. We aimed to verify HBV pre-S deletion
      mutations in relation to the risk of HCC. MATERIAL AND METHODS: We searched the
      commonly used electronic databases for relevant studies of this association among
      the Asian population until September 30th, 2014. Odds ratios (ORs) with 95%
      confidence intervals (CIs) were employed to calculate the association. RESULTS: A
      total of 17 case-control studies were screened out, including 2837 HBV-infected
      patients, of whom 1246 had HCC. The results showed that the frequency of pre-S
      deletion of HBV in patients with HCC was higher than that in patients without HCC
      (35.7% vs. 11.5%), indicating the prevalence of this mutation in patients with
      HCC. Statistically significant correlations were observed for pre-S deletion
      mutation and risk of HCC in a random-effects model (OR=3.90, 95% CI=2.80-5.44,
      P<0.00001). This association was also found in Chinese populations (OR=4.84, 95%
      CI=2.86-8.20, P<0.00001). CONCLUSIONS: Our data indicate that HBV pre-S deletion
      mutations might be associated with HCC risk. Their oncogenic role may be
      important in studying the potential mechanism of HBV hepatocarcinogenesis.

PMID- 25868852
TI  - Loss of INPP4B causes a DNA repair defect through loss of BRCA1, ATM and ATR and
      can be targeted with PARP inhibitor treatment.
AB  - Treatment options for ovarian cancer patients remain limited and overall survival
      is less than 50% despite recent clinical advances. The lipid phosphatase inositol
      polyphosphate 4-phosphatase type II (INPP4B) has been described as a tumor
      suppressor in the PI3K/Akt pathway with loss of expression found most pronounced
      in breast, ovarian cancer and melanoma. Using microarray technology we identified
      a DNA repair defect in INPP4B-deficient cells, which we further characterized by
      comet assays and quantification of gammaH2AX, RAD51 and 53BP1 foci formation.
      INPP4B loss resulted in significantly increased sensitivity towards PARP
      inhibition, comparable to loss of BRCA1 in two- and three-dimensional in vitro
      models, as well as in in vivo xenograft models. Mechanistically, we discovered
      that INPP4B forms a protein complex with the key players of DNA repair, ATR and
      BRCA1, in GST pulldown and 293T overexpression assays, and INPP4B loss affects
      BRCA1, ATM and ATR protein stability resulting in the observed DNA repair defect.
      Given that INPP4B loss has been found in 40% of ovarian cancer patients, this
      study provides the rationale for establishing INPP4B as a biomarker of PARP
      inhibitor response, and consequently offers novel therapeutic options for a
      significant subset of patients. Loss of the tumor suppressor inositol
      polyphosphate 4-phosphatase type II (INPP4B) results in a DNA repair defect due
      to concomitant loss of BRCA1, ATR and ATM and can be therapeutically targeted
      with PARP inhibitors. 

PMID- 25868853
TI  - Cordycepin (3'-deoxyadenosine) suppressed HMGA2, Twist1 and ZEB1-dependent
      melanoma invasion and metastasis by targeting miR-33b.
AB  - Malignant melanoma, the most deadly form of skin cancer, has a high propensity
      for metastatic spread and is notoriously chemotherapy-resistant. Cordycepin, the
      active component of Cordyceps spp., has been identified to have anti-metastatic
      effect on tumor progression and thus possesses pharmacological and therapeutic
      potentials. However, the mechanisms of anti-metastatic effects of cordycepin at
      cellular levels remain elusive. We analyzed the effect of cordycepin on human
      melanoma miRNA expression profiles by miRNAarray and found that miR-33b was
      upregulated in highly-metastatic melanoma cell lines following cordycepin
      exposure. Cordycepin-mediated miR-33b expression was dependent on LXR-RXR
      heterodimer activation. miR-33b directly binds to HMGA2, Twist1 and ZEB1 3'-UTR
      to suppress their expression. The negative correlations between miR-33b levels
      and HMGA2, Twist1 or ZEB1 expression were detected in 72 patient melanoma tissue
      samples. By targeting HMGA2 and Twist1, miR-33b attenuated melanoma migration and
      invasiveness upon cordycepin exposure. miR-33b knockdown or ZEB1 overexpression
      reverted cordycepin-mediated mesenchymal-epithelial transition (MET), triggering
      the expression of N-cadherin. In spontaneous metastasis models, cordycepin
      suppressed tumor metastasis without altering primary tumor growth. We showed for
      the first time that targeting miRNA by cordycepin indicates a new mechanism of
      cordycepin-induced suppression of tumor metastasis and miR-33b/HMGA2/Twist1/ZEB1
      axis plays critical roles in regulating melanoma dissemination. 

PMID- 25868854
TI  - Powerful anti-tumor and anti-angiogenic activity of a new anti-vascular
      endothelial growth factor receptor 1 peptide in colorectal cancer models.
AB  - To assess the therapeutic outcome of selective block of VEGFR1, we have evaluated
      the activity of a new specific antagonist of VEGFR1, named iVR1 (inhibitor of
      VEGFR1), in syngenic and xenograft colorectal cancer models, in an artificial
      model of metastatization, and in laser-induced choroid neovascularization. iVR1
      inhibited tumor growth and neoangiogenesis in both models of colorectal cancer,
      with an extent similar to that of bevacizumab, a monoclonal antibody anti-VEGF-A.
      It potently inhibited VEGFR1 phosphorylation in vivo, determining a strong
      inhibition of the recruitment of monocyte-macrophages and of mural cells as
      confirmed, in vitro, by the ability to inhibit macrophages migration. iVR1 was
      able to synergize with irinotecan determining a shrinkage of tumors that became
      undetectable after three weeks of combined treatment. Such treatment induced a
      significant prolongation of survival similar to that observed with bevacizumab
      and irinotecan combination. iVR1 also fully prevented lung invasion by HCT-116
      cells injected in mouse tail vein. Also, iVR1 impressively inhibited choroid
      neovascularization after a single intravitreal injection. Collectively, data
      showed the strong potential of iVR1 peptide as a new anti-tumor and anti
      metastatic agent and demonstrate the high flexibility of VEGFR1 antagonists as
      therapeutic anti-angiogenic agents in different pathological contexts. 

PMID- 25868855
TI  - ROS1 rearrangements in lung adenocarcinoma: prognostic impact, therapeutic
      options and genetic variability.
AB  - BACKGROUND: While recent data show that crizotinib is highly effective in
      patients with ROS1 rearrangement, few data is available about the prognostic
      impact, the predictive value for different treatments, and the genetic
      heterogeneity of ROS1-positive patients. PATIENTS AND METHODS: 1137 patients with
      adenocarcinoma of the lung were analyzed regarding their ROS1 status. In positive
      cases, next-generation sequencing (NGS) was performed. Clinical characteristics,
      treatments and outcome of these patients were assessed. Overall survival (OS) was
      compared with genetically defined subgroups of ROS1-negative patients. RESULTS:
      19 patients of 1035 evaluable (1.8%) had ROS1-rearrangement. The median OS has
      not been reached. Stage IV patients with ROS1-rearrangement had the best OS of
      all subgroups (36.7 months, p < 0.001). 9 of 14 (64.2%) patients had at least one
      response to chemotherapy. Estimated mean OS for patients receiving chemotherapy
      and crizotinib was 5.3 years. Ten patients with ROS1-rearrangement (52.6%)
      harbored additional aberrations. CONCLUSION: ROS1-rearangement is not only a
      predictive marker for response to crizotinib, but also seems to be the one of the
      best prognostic molecular markers in NSCLC reported so far. In stage IV patients,
      response to chemotherapy was remarkable high and overall survival was
      significantly better compared to other subgroups including EGFR-mutated and ALK
      fusion-positive NSCLC.

PMID- 25868856
TI  - Rampant centrosome amplification underlies more aggressive disease course of
      triple negative breast cancers.
AB  - Centrosome amplification (CA), a cell-biological trait, characterizes pre
      neoplastic and pre-invasive lesions and is associated with tumor aggressiveness.
      Recent studies suggest that CA leads to malignant transformation and promotes
      invasion in mammary epithelial cells. Triple negative breast cancer (TNBC), a
      histologically-aggressive subtype shows high recurrence, metastases, and
      mortality rates. Since TNBC and non-TNBC follow variable kinetics of metastatic
      progression, they constitute a novel test bed to explore if severity and nature
      of CA can distinguish them apart. We quantitatively assessed structural and
      numerical centrosomal aberrations for each patient sample in a large-cohort of
      grade-matched TNBC (n = 30) and non-TNBC (n = 98) cases employing multi-color
      confocal imaging. Our data establish differences in incidence and severity of CA
      between TNBC and non-TNBC cell lines and clinical specimens. We found strong
      correlation between CA and aggressiveness markers associated with metastasis in
      20 pairs of grade-matched TNBC and non-TNBC specimens (p < 0.02). Time-lapse
      imaging of MDA-MB-231 cells harboring amplified centrosomes demonstrated enhanced
      migratory ability. Our study bridges a vital knowledge gap by pinpointing that CA
      underlies breast cancer aggressiveness. This previously unrecognized organellar
      inequality at the centrosome level may allow early-risk prediction and explain
      higher tumor aggressiveness and mortality rates in TNBC patients. 

PMID- 25868857
TI  - The oncogenic role of JC virus T antigen in lens tumors without cell specificity
      of alternative splicing of its intron.
AB  - JC virus (JCV), a ubiquitous polyoma virus that commonly infects the human, is
      identified as the etiologic agent for progressive multifocal leukoencephalopathy
      and some malignancies. To clarify the oncogenic role of JCV T antigen, we
      established two transgenic mice of T antigen using either alpha-crystallin A
      (alphaAT) or cytokeratin 19(KT) promoter. Lens tumors were found in high-copy
      alphaAT mice with the immunopositivity of T antigen, p53, beta-catenin and N
      cadherin. Enlarged eyeballs were observed and tumor invaded into the brain by
      magnetic resonance imaging and hematoxylin-and-eosin staining. The overall
      survival time of homozygous mice was shorter than that of hemizygous mice
      (p<0.01), the latter than wild-type mice (p<0.01). The spontaneous salivary tumor
      and hepatocellular carcinoma were seen in alphaAT5 transgenic mice with no
      positivity of T antigen. KT7 mice suffered from lung tumor although JCV T antigen
      was strongly expressed in gastric epithelial cells. The alternative splicing of T
      antigen intron was detectable in the lens tumor of alphaAT mice, gastric mucosa
      of KT mice, and various cells transfected with pEGFP-N1-T antigen. It was
      suggested that JCV T antigen might induce carcinogenesis at a manner of cell
      specificity, which is not linked to alternative splicing of its intron. Both
      spontaneous lens and lung tumor models provide good tools to investigate the
      oncogenic role of JCV T antigen.

PMID- 25868858
TI  - Oncogenic extracellular HSP70 disrupts the gap-junctional coupling between
      capillary cells.
AB  - High levels of circulating heat shock protein 70 (HSP70) are detected in many
      cancers. In order to explore the effects of extracellular HSP70 on human
      microvascular endothelial cells (HMEC), we initially used gap-FRAP technique.
      Extracellular human HSP70 (rhHSP70), but not rhHSP27, blocks the gap-junction
      intercellular communication (GJIC) between HMEC, disrupts the structural
      integrity of HMEC junction plaques, and decreases connexin43 (Cx43) expression,
      which correlates with the phosphorylation of Cx43 serine residues. Further
      exploration of these effects identified a rapid transactivation of the Epidermal
      Growth Factor Receptor in a Toll-Like Receptor 4-dependent manner, preceding its
      internalization. In turn, cytosolic Ca2+ oscillations are generated. Both GJIC
      blockade and Ca2+ mobilization partially depend on ATP release through Cx43 and
      pannexin (Panx-1) channels, as demonstrated by blocking activity or expression of
      channels, and inactivating extracellular ATP. By monitoring dye-spreading into
      adjacent cells, we show that HSP70 released from human monocytes in response to
      macrophage colony-stimulating factor, prevents the formation of GJIC between
      monocytes and HMEC. Therapeutic manipulation of this pathway could be of interest
      in inflammatory and tumor growth. 

PMID- 25868859
TI  - Critical role of gap junction communication, calcium and nitric oxide signaling
      in bystander responses to focal photodynamic injury.
AB  - Ionizing and nonionizing radiation affect not only directly targeted cells but
      also surrounding "bystander" cells. The underlying mechanisms and therapeutic
      role of bystander responses remain incompletely defined. Here we show that
      photosentizer activation in a single cell triggers apoptosis in bystander cancer
      cells, which are electrically coupled by gap junction channels and support the
      propagation of a Ca2+ wave initiated in the irradiated cell. The latter also acts
      as source of nitric oxide (NO) that diffuses to bystander cells, in which NO
      levels are further increased by a mechanism compatible with Ca(2+)-dependent
      enzymatic production. We detected similar signals in tumors grown in dorsal
      skinfold chambers applied to live mice. Pharmacological blockade of connexin
      channels significantly reduced the extent of apoptosis in bystander cells,
      consistent with a critical role played by intercellular communication, Ca2+ and
      NO in the bystander effects triggered by photodynamic therapy.

PMID- 25868861
TI  - Structural, photophysical and magnetic properties of transition metal complexes
      based on the dipicolylamino-chloro-1,2,4,5-tetrazine ligand.
AB  - The ligand 3-chloro-6-dipicolylamino-1,2,4,5-tetrazine (Cl-TTZ-dipica) , prepared
      by the direct reaction between 3,6-dichloro-1,2,4,5-tetrazine and di(2-picolyl)
      amine, afforded a series of four neutral transition metal complexes formulated as
      [Cl-TTZ-dipica-MCl2]2, with M = Zn(II), Cd(II), Mn(II) and Co(II), when reacted
      with the corresponding metal chlorides. The dinuclear structure of the
      isostructural complexes was disclosed by single crystal X-ray analysis, clearly
      indicating the formation of [M(II)-(MU-Cl)2M(II)] motifs and the involvement of
      the amino nitrogen atom in semi-coordination with the metal centers, thus leading
      to distorted octahedral coordination geometries. Moreover, the chlorine atoms,
      either coordinated to the metal or as a substituent on the tetrazine ring, engage
      respectively in specific anion-pi intramolecular and intermolecular interactions
      with the electron-poor tetrazine units in the solid state, thus controlling the
      supramolecular architecture. Modulation of the emission properties is observed in
      the case of the Zn(II) and Cd(II) complexes when compared to the free ligand. A
      striking difference is observed in the magnetic properties of the Mn(II) and
      Co(II) complexes. An antiferromagnetic coupling takes place in the
      dimanganese(II) compound (J = -1.25 cm(-1)) while the Co(II) centers are
      ferromagnetically coupled in the corresponding complex (J = +0.55 cm(-1)), the
      spin Hamiltonian being defined as H = -JSA.SB.

PMID- 25868862
TI  - Src and SCC: getting to the FAKs.

PMID- 25868860
TI  - The SOX17/miR-371-5p/SOX2 axis inhibits EMT, stem cell properties and metastasis
      in colorectal cancer.
AB  - Cancer stem cells (CSCs) and EMT-type cells, which share molecular
      characteristics with CSCs, have been believed to play critical roles in tumor
      metastasis. Although much progress has been garnered in elucidating the molecular
      pathways that trigger EMT, stemness and metastasis, a number of key mechanistic
      gaps remain elusive. In the study, miR-371-5p was obviously down-regulated in
      primary CRC tissues compared with matched adjacent normal mucosa and correlated
      significantly with differentiation, tumor size, lymphatic and liver metastases.
      MiR-371-5p could attenuate proliferation, invasion in vitro and metastasis in
      vivo in CRC cells. It also suppressed EMT by regulating Wnt/beta-catenin
      signaling and strongly decreased the CRC stemness phenotypes. Moreover,
      demethylation of SOX17 induced miR-371-5p expression and consequently suppressed
      its direct target SOX2 in CRC cells. MiR-371-5p was necessary for SOX17 mediated
      cancer-related traits and SOX2 was a functional target of miR-371-5p. A positive
      relationship between SOX17 and miR-371-5p expression and a negative one between
      miR-371-5p and SOX2 expression were observed in CRC cell lines and tissues. In
      conclusion, we identified miR-371-5p as an important "oncosuppressor" in CRC
      progression and elucidated a novel mechanism of the SOX17/miR-371-5p/SOX2 axis in
      the regulation of EMT, stemness and metastasis, which may be a potential
      therapeutic target. 

PMID- 25868863
TI  - The impact of composite AUC estimates on the prediction of systemic exposure in
      toxicology experiments.
AB  - Current toxicity protocols relate measures of systemic exposure (i.e. AUC, Cmax)
      as obtained by non-compartmental analysis to observed toxicity. A complicating
      factor in this practice is the potential bias in the estimates defining safe drug
      exposure. Moreover, it prevents the assessment of variability. The objective of
      the current investigation was therefore (a) to demonstrate the feasibility of
      applying nonlinear mixed effects modelling for the evaluation of toxicokinetics
      and (b) to assess the bias and accuracy in summary measures of systemic exposure
      for each method. Here, simulation scenarios were evaluated, which mimic
      toxicology protocols in rodents. To ensure differences in pharmacokinetic
      properties are accounted for, hypothetical drugs with varying disposition
      properties were considered. Data analysis was performed using non-compartmental
      methods and nonlinear mixed effects modelling. Exposure levels were expressed as
      area under the concentration versus time curve (AUC), peak concentrations (Cmax)
      and time above a predefined threshold (TAT). Results were then compared with the
      reference values to assess the bias and precision of parameter estimates. Higher
      accuracy and precision were observed for model-based estimates (i.e. AUC, Cmax
      and TAT), irrespective of group or treatment duration, as compared with non
      compartmental analysis. Despite the focus of guidelines on establishing safety
      thresholds for the evaluation of new molecules in humans, current methods neglect
      uncertainty, lack of precision and bias in parameter estimates. The use of
      nonlinear mixed effects modelling for the analysis of toxicokinetics provides
      insight into variability and should be considered for predicting safe exposure in
      humans. 

PMID- 25868865
TI  - Expression of FGFR1 is an independent prognostic factor in triple-negative breast
      cancer.
AB  - Triple-negative breast cancers (TNBCs) are clinically aggressive tumors with
      limited treatment options. We examined the clinicopathological associations and
      prognostic implications of FGFR1 and FGFR2 expression in TNBCs. Tissue
      microarrays constructed from TNBCs were immunostained with FGFR1 and FGFR2, and
      scored by intensity and percentage of tumor cells stained per intensity for each
      subcellular compartment, which were correlated with clinicopathological
      parameters and survival. Cell migration following siRNA-mediated silencing of the
      FGFR1 gene in TNBC cell lines was also performed. 714 cases were informative for
      FGFR1 and FGFR2 immunostaining. Thresholds were defined as at least 1 % of cells
      stained and H-score of 100 or more. Proportions positive by each threshold were,
      respectively, 89.9 %, 7.1 % for FGFR1 (cytoplasm); 36.8 %, 7.8 % for FGFR2
      (cytoplasm); and 33.5 %, 5.2 % for FGFR2 (membrane). Significant associations
      included FGFR1 and FGFR2 immunostaining for lobular subtype, FGFR2 immunostaining
      with lower grade, and more basal-like cancers with H-scores of 100 or more FGFR1
      immunostaining. Multivariate Cox regression analysis showed FGFR1 expression in
      TNBCs to be independently prognostic for overall survival (OS) at both
      thresholds. Cases completely negative (less than 1 % staining) for FGFR1
      immunostaining showed improved OS, while those with H-score of 100 or more
      immunostaining had the worst OS. Cell line studies revealed up-regulation of the
      FGFR1 gene in the MDA-MB-231 and Hs578T TNBC cells, and specific knockdown of
      FGFR1 expression significantly reduced cell migration in MDA-MB-231 cell line. In
      conclusion, FGFR1 expression in TNBCs is independently prognostic of OS, and H
      score of 100 or more FGFR1 immunostaining may define tumors that have treatment
      potential via FGFR signaling inhibition. 

PMID- 25868866
TI  - An open letter to panels that are deciding guidelines for breast cancer
      screening.
AB  - Panels are presently reviewing breast cancer screening guidelines. It is critical
      that they understand which publications are scientifically valid, and which
      analyses are methodologically flawed and not valid. The scientific evidence
      clearly supports annual mammography screening beginning at the age of 40. The
      analyses that suggest that screening leads to overdiagnosis of invasive breast
      cancers are flawed and incorrect. There is little if any overdiagnosis of these
      cancers. The vast majority of breast cancers occur in women who are not at
      elevated risk so that excluding them from screening and only screening high risk
      women will deny the benefits of early detection to most women who develop breast
      cancer. Guidelines panels should not make decisions that exclude women from
      screening. Women should be provided with accurate information so that they can
      make informed decisions and have unimpeded access to screening if that is their
      preference. 

PMID- 25868867
TI  - Factors associated with genetic counseling and BRCA testing in a population-based
      sample of young Black women with breast cancer.
AB  - Concerns about the potential for genomic advances to increase health disparities
      have been raised. Thus, it is important to assess referral and uptake of genetic
      counseling (GC) and testing in minority populations at high risk for hereditary
      breast and ovarian cancer (HBOC). Black women diagnosed with invasive breast
      cancer <=age 50 in 2009-2012 were recruited through the Florida State Cancer
      Registry 6-18 months following diagnosis and completed a baseline questionnaire.
      Summary statistics, Chi-square tests, and path modeling were conducted to examine
      which demographic and clinical variables were associated with referral and access
      to genetic services. Of the 440 participants, all met national criteria for GC,
      yet only 224 (51 %) were referred for or received GC and/or HBOC testing.
      Variables most strongly associated with healthcare provider referral for GC
      included having a college education (OR 2.1), diagnosis at or below age 45 (OR
      2.0), and triple negative tumor receptor status (OR 1.7). The strongest
      association with receipt of GC and/or HBOC testing was healthcare provider
      referral (OR 7.9), followed by private health insurance at diagnosis (OR 2.8),
      and household income greater than $35,000 in the year prior to diagnosis (OR
      2.0). Study findings suggest efforts are needed to improve genetic services
      access among a population-based sample of high-risk Black women. These results
      indicate that socioeconomic factors and physician referral patterns contribute to
      disparities in access to genetic services within this underserved minority
      population. 

PMID- 25868868
TI  - Self esteem and self agency in first episode psychosis: Ethnic variation and
      relationship with clinical presentation.
AB  - The impact of self esteem and Locus of Control (LoC) on clinical presentation
      across different ethnic groups of patients at their first psychotic episode (FEP)
      remains unknown. We explored these constructs in 257 FEP patients (Black n=95;
      White British n=119) and 341 controls (Black n=70; White British n=226), and
      examined their relationship with symptom dimensions and pathways to care. FEP
      patients presented lower self-esteem and a more external LoC than controls. Lower
      self esteem was associated with a specific symptoms profile (more manic and less
      negative symptoms), and with factors predictive of poorer outcome (longer
      duration of untreated psychosis (DUP) and compulsory mode of admission). A more
      external LoC was associated with more negative symptoms and an insidious onset.
      When we explored these constructs across different ethnic groups, we found that
      Black patients had significantly higher self esteem than White British. This was
      again associated with specific symptom profiles. While British patients with
      lower self esteem were more likely to report delusions, hallucinations and
      negative symptoms, Black patients with a lower self esteem showed less
      disorganization symptoms. These findings suggest that self esteem and LoC may
      represent one way in which social experiences and contexts differentially
      influence vulnerable individuals along the pathway to psychosis. 

PMID- 25868869
TI  - Exploring Sleep Quality and Related Factors in Chinese Midlife Women.
AB  - We investigated the percentage of women with poor sleep quality and its related
      factors among mainland Chinese women. Sleep quality and menopausal status were
      self-reported. We explored the contribution of possible risk factors, including
      sociodemographic characteristics, comorbidities, lifestyle, psychological status,
      stressful life events, and vasomotor symptoms. We found that 38.6% of midlife
      Chinese women were poor sleepers. This percentage was higher in comparison with
      women from other Asian countries. Our multiple logistic regression showed that
      anxiety, comorbidities, perceived stress, and vasomotor symptoms were risk
      factors for poor sleep quality.

PMID- 25868870
TI  - Iron oxide-decorated carbon for supercapacitor anodes with ultrahigh energy
      density and outstanding cycling stability.
AB  - Supercapacitor with ultrahigh energy density (e.g., comparable with those of
      rechargeable batteries) and long cycling ability (>50000 cycles) is attractive
      for the next-generation energy storage devices. The energy density of
      carbonaceous material electrodes can be effectively improved by combining with
      certain metal oxides/hydroxides, but many at the expenses of power density and
      long-time cycling stability. To achieve an optimized overall electrochemical
      performance, rationally designed electrode structures with proper control in
      metal oxide/carbon are highly desirable. Here we have successfully realized an
      ultrahigh-energy and long-life supercapacitor anode by developing a hierarchical
      graphite foam-carbon nanotube framework and coating the surface with a thin layer
      of iron oxide (GF-CNT@Fe2O3). The full cell of anode based on this structure
      gives rise to a high energy of ~74.7 Wh/kg at a power of ~1400 W/kg, and ~95.4%
      of the capacitance can be retained after 50000 cycles of charge-discharge. These
      performance features are superior among those reported for metal oxide based
      supercapacitors, making it a promising candidate for the next generation of high
      performance electrochemical energy storage. 

PMID- 25868871
TI  - Thoracoscopic and Laparoscopic Enucleation of Esophageal Leiomyomas.
AB  - Although infrequent, esophageal leiomyomas are the most common benign intramural
      tumors of the esophagus. As malignant potential is not a concern in these
      lesions, they represent ideal candidates for an organ-preserving approach. Due to
      their well-circumscribed growth, a minimally invasive approach should be pursued
      in almost all patients. We present our recent techniques and results associated
      with totally minimally invasive thoracoscopic and laparoscopic approaches to
      resection of esophageal leiomyomas. These approaches require technical expertise
      but can be accomplished with a short learning curve. 

PMID- 25868872
TI  - Computational modeling analysis of mitochondrial superoxide production under
      varying substrate conditions and upon inhibition of different segments of the
      electron transport chain.
AB  - A computational mechanistic model of superoxide (O2*-) formation in the
      mitochondrial electron transport chain (ETC) was developed to facilitate the
      quantitative analysis of factors controlling mitochondrial O2*- production and
      assist in the interpretation of experimental studies. The model takes into
      account all individual electron transfer reactions in Complexes I and III. The
      model accounts for multiple, often seemingly contradictory observations on the
      effects of DeltaPsi and DeltapH, and for the effects of multiple substrate and
      inhibitor conditions, including differential effects of Complex III inhibitors
      antimycin A, myxothiazol and stigmatellin. Simulation results confirm that, in
      addition to O2*- formation in Complex III and at the flavin site of Complex I,
      the quinone binding site of Complex I is an additional superoxide generating site
      that accounts for experimental observations on O2*- production during reverse
      electron transfer. However, our simulation results predict that, when cytochrome
      c oxidase is inhibited during oxidation of succinate, ROS production at this site
      is eliminated and almost all superoxide in Complex I is generated by reduced FMN,
      even when the redox pressure for reverse electron transfer from succinate is
      strong. In addition, the model indicates that conflicting literature data on the
      kinetics of electron transfer in Complex III involving the iron-sulfur protein
      cytochrome bL complex can be resolved in favor of a dissociation of the protein
      only after electron transfer to cytochrome bH. The model predictions can be
      helpful in understanding factors driving mitochondrial superoxide formation in
      intact cells and tissues.

PMID- 25868875
TI  - Respective effects of oxygen and energy substrate deprivation on beta cell
      viability.
AB  - Deficit in oxygen and energetic substrates delivery is a key factor in islet loss
      during islet transplantation. Permeability transition pore (PTP) is a
      mitochondrial channel involved in cell death. We have studied the respective
      effects of oxygen and energy substrate deprivation on beta cell viability as well
      as the involvement of oxidative stress and PTP opening. Energy substrate
      deprivation for 1h followed by incubation in normal conditions led to a
      cyclosporin A (CsA)-sensitive-PTP-opening in INS-1 cells and human islets. Such a
      procedure dramatically decreased INS-1 cells viability except when transient
      removal of energy substrates was performed in anoxia, in the presence of
      antioxidant N-acetylcysteine (NAC) or when CsA or metformin inhibited PTP
      opening. Superoxide production increased during removal of energy substrates and
      increased again when normal energy substrates were restored. NAC, anoxia or
      metformin prevented the two phases of oxidative stress while CsA prevented the
      second one only. Hypoxia or anoxia alone did not induce oxidative stress, PTP
      opening or cell death. In conclusion, energy substrate deprivation leads to an
      oxidative stress followed by PTP opening, triggering beta cell death.
      Pharmacological prevention of PTP opening during islet transplantation may be a
      suitable option to improve islet survival and graft success. 

PMID- 25868876
TI  - Safety and performance of a novel embolic deflection device in patients
      undergoing transcatheter aortic valve replacement: results from the DEFLECT I
      study.
AB  - AIMS: This study aimed to evaluate the safety and performance of the TriGuardTM
      Embolic Deflection Device (EDD), a nitinol mesh filter positioned in the aortic
      arch across all three major cerebral artery take-offs to deflect emboli away from
      the cerebral circulation, in patients undergoing transcatheter aortic valve
      replacement (TAVR). METHODS AND RESULTS: The prospective, multicentre DEFLECT I
      study (NCT01448421) enrolled 37 consecutive subjects undergoing TAVR with the
      TriGuard EDD. Subjects underwent clinical and cognitive follow-up to 30 days;
      cerebral diffusion-weighted magnetic resonance imaging (DW-MRI) was performed pre
      procedure and at 4+/-2 days post procedure. The device performed as intended with
      successful cerebral coverage in 80% (28/35) of cases. The primary safety endpoint
      (in-hospital EDD device- or EDD procedure-related cardiovascular mortality, major
      stroke disability, life-threatening bleeding, distal embolisation, major vascular
      complications, or need for acute cardiac surgery) occurred in 8.1% of subjects
      (VARC-defined two life-threatening bleeds and one vascular complication). The
      presence of new cerebral ischaemic lesions on post-procedure DW-MRI (n=28) was
      similar to historical controls (82% vs. 76%, p=NS). However, an exploratory
      analysis found that per-patient total lesion volume was 34% lower than reported
      historical data (0.2 vs. 0.3 cm3), and 89% lower in patients with complete (n=17)
      versus incomplete (n=10) cerebral vessel coverage (0.05 vs. 0.45 cm3, p=0.016).
      CONCLUSIONS: Use of the first-generation TriGuard EDD during TAVR is safe, and
      device performance was successful in 80% of cases during the highest embolic-risk
      portions of the TAVR procedure. The potential of the TriGuard EDD to reduce total
      cerebral ischaemic burden merits further randomised investigation.

PMID- 25868874
TI  - Uncoupling, metabolic inhibition and induction of mitochondrial permeability
      transition in rat liver mitochondria caused by the major long-chain hydroxyl
      monocarboxylic fatty acids accumulating in LCHAD deficiency.
AB  - Patients with long-chain 3-hydroxy-acyl-CoA dehydrogenase (LCHAD) deficiency
      commonly present liver dysfunction whose pathogenesis is unknown. We studied the
      effects of long-chain 3-hydroxylated fatty acids (LCHFA) that accumulate in LCHAD
      deficiency on liver bioenergetics using mitochondrial preparations from young
      rats. We provide strong evidence that 3-hydroxytetradecanoic (3HTA) and 3
      hydroxypalmitic (3HPA) acids, the monocarboxylic acids that are found at the
      highest tissue concentrations in this disorder, act as metabolic inhibitors and
      uncouplers of oxidative phosphorylation. These conclusions are based on the
      findings that these fatty acids decreased ADP-stimulated (state 3) and uncoupled
      respiration, mitochondrial membrane potential and NAD(P)H content, and, in
      contrast, increased resting (state 4) respiration. We also verified that 3HTA and
      3HPA markedly reduced Ca2+ retention capacity and induced swelling in Ca2+-loaded
      mitochondria. These effects were mediated by mitochondrial permeability
      transition (MPT) induction since they were totally prevented by the classical MPT
      inhibitors cyclosporin A and ADP, as well as by ruthenium red, a Ca2+ uptake
      blocker. Taken together, our data demonstrate that the major monocarboxylic LCHFA
      accumulating in LCHAD deficiency disrupt energy mitochondrial homeostasis in the
      liver. It is proposed that this pathomechanism may explain at least in part the
      hepatic alterations characteristic of the affected patients.

PMID- 25868873
TI  - Semiquinone intermediates are involved in the energy coupling mechanism of E.
      coli complex I.
AB  - Complex I (NADH:quinone oxidoreductase) is central to cellular aerobic energy
      metabolism, and its deficiency is involved in many human mitochondrial diseases.
      Complex I translocates protons across the membrane using electron transfer
      energy. Semiquinone (SQ) intermediates appearing during catalysis are suggested
      to be key for the coupling mechanism in complex I. However, the existence of SQ
      has remained controversial due to the extreme difficulty in detecting unstable
      and low intensity SQ signals. Here, for the first time with Escherichia coli
      complex I reconstituted in proteoliposomes, we successfully resolved and
      characterized three distinct SQ species by EPR. These species include: fast
      relaxing SQ (SQNf) with P1/2 (half-saturation power level)>50mW and a wider
      linewidth (12.8 G); slow-relaxing SQ (SQNs) with P1/2=2-3mW and a 10G linewidth;
      and very slow-relaxing SQ (SQNvs) with P1/2= ~0.1mW and a 7.5G linewidth. The
      SQNf signals completely disappeared in the presence of the uncoupler gramicidin D
      or squamotacin, a potent E. coli complex I inhibitor. The pH dependency of the
      SQNf signals correlated with the proton-pumping activities of complex I. The SQNs
      signals were insensitive to gramicidin D, but sensitive to squamotacin. The SQNvs
      signals were insensitive to both gramicidin D and squamotacin. Our deuterium
      exchange experiments suggested that SQNf is neutral, while SQNs and SQNvs are
      anion radicals. The SQNs signals were lost in the DeltaNuoL mutant missing
      transporter module subunits NuoL and NuoM. The roles and relationships of the SQ
      intermediates in the coupling mechanism are discussed. 

PMID- 25868877
TI  - Myocardial perfusion grade predicts final infarct size and left ventricular
      function in patients with ST-elevation myocardial infarction treated with a
      pharmaco-invasive strategy (thrombolysis and early angioplasty).
AB  - AIMS: Primary percutaneous coronary intervention (PCI) for ST-elevation
      myocardial infarction (STEMI) usually restores TIMI 3 flow in the occluded
      artery, but microvascular impairment may persist in >30% of patients. Less is
      known about microvascular reperfusion in STEMI patients treated with thrombolysis
      followed by early PCI. We aimed to assess the association between TIMI myocardial
      perfusion (TMP) at the end of the PCI procedure and left ventricular function
      (LVEF) and infarct size after three months in such patients. METHODS AND RESULTS:
      Patients with STEMI treated with thrombolysis and early PCI were included. TMP
      grade was assessed at the end of the PCI procedure, and MRI was performed after
      three months. Of the 89 patients included, 92% (n=82) had TIMI 3 flow at the end
      of the PCI procedure, while only 62% (n=55) had TMP grade 2 or 3. Patients with
      TMP grade 2-3 had significantly higher LVEF (59% [53-67] vs. 50% [41-56],
      p<0.0001) and smaller infarct size (8.3 ml [2.7-15.5] vs. 20.7 ml [13.0-36.0],
      p<0,0001) after three months. CONCLUSIONS: In STEMI patients treated with
      thrombolysis and early PCI, the TMP grade at the end of the PCI procedure was
      significantly associated with LVEF and infarct size after three months.

PMID- 25868878
TI  - A Global Oral Health Survey of professional opinion using the International
      Classification of Functioning, Disability and Health.
AB  - OBJECTIVES: The concept of oral health is frequently reduced to the absence of
      disease, despite existing conceptual models exploring the wider determinants of
      oral health and quality of life. The International Classification of Functioning,
      Disability and Health (ICF) (WHO) is designed to qualify functional, social and
      environmental aspects of health. This survey aimed to reach a consensual
      description of adult oral health, derived from the ICF using international
      professional opinion. METHODS: The Global Oral Health Survey involved a two
      round, online survey concerning factors related to oral health including
      functioning, participation and social environment. Four hundred eighty-six oral
      health professionals from 74 countries registered online. Professionals were
      pooled into 18 groups of six WHO world regions and three professional groups. In
      a randomised stratification process, eight professionals from each pool (n=144)
      completed the survey. The first round consisted of eight open-ended questions.
      Open expression replies were analysed for meaningful concepts and linked using
      established rules to the ICF. In Round 2, items were rated for their relevance to
      oral health (88% response rate). RESULTS: Eighty-nine ICF items and 30 other
      factors were considered relevant by at least 80% of participants. International
      professionals reached consensus on a holistic description of oral health, which
      could be qualified and quantified using the ICF. CONCLUSIONS: These results
      represent the first step towards developing an ICF Core Set in Oral Health, which
      would provide a practical tool for reporting outcome measures in clinical
      practice, for research and epidemiology, and for the improvement of
      interdisciplinary communication regarding oral health. CLINICAL SIGNIFICANCE:
      Professional consensus reached in this survey is the foundation stone for
      developing an ICF Core Set in Oral Health, allowing the holistic aspects of oral
      health to be qualified and quantified. This tool is necessary to widen our
      approach to clinical decision making, measurement of clinical outcomes, research
      and epidemiology.

PMID- 25868879
TI  - Clinical enamel surface changes following an intra-oral acidic challenge.
AB  - OBJECTIVES: Investigation of early enamel erosion using replica impressions to
      compare changes in enamel surface topography in vivo prior to and over a 24 h
      period following acid challenge. METHOD: A single treatment, blinded, enamel
      replica clinical study was undertaken in 20 healthy subjects. Replica tooth
      impressions were taken at baseline, following acid challenge and 2, 4, 7 and 24 h
      post challenge. Subjects consumed 500 ml of acidic soft drink over 30 min.
      Scanning electron microscopy of surface tomography was characterised with a
      descriptive 5 point scale by four judges. Duplicate impressions were taken to
      assess reproducibility. RESULTS: 18 subjects had scorable sequences. Descriptive
      analyses showed erosive changes following acid consumption and reparative changes
      in the subsequent 24 h period. Comparing baseline replica to the 24 h replica,
      there were no significant differences (p=0.26) in tooth surface characteristics.
      Comparing the replica taken immediately following acidic challenge with the
      subsequent replicas at 2, 4, 7 and 24 h, showed clear reduction of erosive
      effects on the enamel surface at 2 h (p=0.02) and a highly significant reduction
      at 4, 7 and 24 h (p<0.001). CONCLUSION: This methodology demonstrated the ability
      to follow the progression and recovery of early erosive enamel lesions over 24 h
      being accurate and reproducible. This study suggests enamel repair commences
      within 2 h following a substantial acidic challenge and is completed 4-24 h
      later. After 24 h, the tooth surface appeared visibly indistinguishable from the
      original tooth surface, suggestive of a recovery process occurring. CLINICAL
      SIGNIFICANCE: Healthy erosive lifestyles often culminate in tooth wear. The time
      taken for enamel remineralisation following acidic challenge is unknown however,
      this study suggests the repair process is relatively slow following a substantial
      acidic challenge, and at least 4-24 h should elapse prior to further acidic
      consumption to allow for recovery.

PMID- 25868880
TI  - Correlation of diffusion tensor imaging and phase-contrast MR with clinical
      parameters of cervical spinal cord injuries.
AB  - STUDY DESIGN: This is a cross-sectional study. OBJECTIVES: The goal of this study
      was to characterize the diffusion properties across segments of the spinal cord
      and peak cerebrospinal fluid (CSF) velocities in the stenotic spinal canal, and
      to determine the correlation between these properties and clinical and
      electrophysiological parameters in patients with cervical spinal cord injury
      (SCI). SETTING: This study was conducted in the University teaching hospital.
      METHODS: The study involved 17 patients with cervical SCI. The apparent diffusion
      coefficient (ADC) and fractional anisotropy (FA) of the spinal cord and peak
      systolic and diastolic velocities of CSF were measured at the level of maximum
      compression (region 1) and at the levels above (region 2) and below (region 3)
      the level of injury with no signal change in conventional magnetic resonance
      imaging. Neurological and electrophysiological parameters were measured,
      including American Spinal Injury Association (ASIA) Impairment Scale (AIS), ASIA
      motor score, ASIA sensory score, Modified Barthel Index, Spinal Cord Independence
      Measure III (SCIM III), somatosensory evoked potentials (SSEP) and motor evoked
      potentials (MEP). RESULTS: The ADC was significantly higher and the FA was
      significantly lower in regions 1, 2 and 3 of the SCI patients than in the normal
      controls (P<0.05 each). FA of the level below correlated with AIS, ASIA sensory
      score and SCIM III score, and FA of the level above correlated with SSEP
      latencies and MEP amplitudes (P<0.05 each). The reductions in FA correlated with
      CSF flow, functional measurements and evoked potentials. CONCLUSIONS: Diffusion
      tensor imaging can be used to quantify the proximal and distal extents of spinal
      cord damage. Reductions in FA were correlated with CSF flow, functional
      measurements and evoked potentials.

PMID- 25868881
TI  - Nutrient profile of 23 596 packaged supermarket foods and non-alcoholic beverages
      in Australia and New Zealand.
AB  - OBJECTIVE: To compare the nutrient profile of packaged supermarket food products
      available in Australia and New Zealand. Eligibility to carry health claims and
      relationship between nutrient profile score and nutritional content were also
      evaluated. DESIGN: Nutritional composition data were collected in six major
      Australian and New Zealand supermarkets in 2012. Mean Food Standards Australia
      New Zealand Nutrient Profiling Scoring Criterion (NPSC) scores were calculated
      and the proportion of products eligible to display health claims was estimated.
      Regression analyses quantified associations between NPSC scores and energy
      density, saturated fat, sugar and sodium contents. RESULTS: NPSC scores were
      derived for 23,596 packaged food products (mean score 7.0, range -17 to 53).
      Scores were lower (better nutrient profile) for foods in Australia compared with
      New Zealand (mean 6.6 v. 7.8). Overall, 45% of foods were eligible to carry
      health claims based on NPSC thresholds: 47% in Australia and 41% in New Zealand.
      However, less than one-third of dairy (32%), meat and meat products (28%) and
      bread and bakery products (27.5%) were eligible to carry health claims.
      Conversely, >75% of convenience food products were eligible to carry health
      claims (82.5%). Each two-unit higher NPSC score was associated with higher energy
      density (78 kJ/100 g), saturated fat (0.95 g/100 g), total sugar (1.5 g/100 g)
      and sodium (66 mg/100 g; all P values<0.001). CONCLUSIONS: Fewer than half of all
      packaged foods available in Australia and New Zealand in 2012 met nutritional
      criteria to carry health claims. The few healthy choices available in key staple
      food categories is a concern. Improvements in nutritional quality of foods
      through product reformulation have significant potential to improve population
      diets.

PMID- 25868882
TI  - Editorial.

PMID- 25868883
TI  - The cel and the sorcerer.
AB  - There are more than 3000 categories of 20th century collectibles being bought and
      sold on a daily basis the world over. Among them is art used in the making of
      animated films, cartoons, commercials, and educational media. With its recent
      rise in value, beginning in 1984, animation art has become one of the most sought
      after and valued collectibles and, at the same time, one of the most frequently
      forged. This article concentrates on the images themselves and considers, the
      processes of animation art production and restoration, and how these techniques
      are used in the forensic investigation of the art's authenticity. 

PMID- 25868884
TI  - Do medical examiners determine elder mistreatment as a cause of death?
AB  - This study examines the decision-making process of medical examiners in
      determining elder mistreatment in cases that present to the county morgue. Harris
      County Medical Examiners were surveyed about factors that influence the
      determination whether elder abuse or neglect was a contributor to the cause of
      death. At the time of the survey, all 11 Harris County Medical Examiners
      participated. Of these, 8 did not determine elder abuse or neglect as
      contributing to the cause of death in the 12 months prior to the survey, 6
      reported that medical records were helpful "all the time", 3 reported "most of
      the time", and 2, indicated that the records were "some-times helpful". The
      survey also indicated that information that assists medical examiners in
      identifying the potential for abuse or neglect ranged from "present most of the
      time" to "never present". Multiple factors including autopsy findings, medical
      compliance, inconsistency in injury findings, and malnutrition were reported as
      helpful in determining elder abuse or neglect. Further studies are needed to
      determine additional factors that would provide medical examiners with the
      ability to more readily identify signs of elder abuse or neglect. 

PMID- 25868885
TI  - Sexual dimorphism and population variation in the adult mandible : Forensic
      applications of geometric morphometrics.
AB  - This article forms part of an ongoing series of investigations designed to apply
      three-dimensional (3D) technology to problems in forensic anthropology. We report
      here on new morphometric data examining sexual dimorphism and population
      variation in the adult human mandible. The material is sourced from dissection
      hall subjects of South African and American origin consequently the sex and a
      statement of age are known for each individual. Thirty-eight bilateral 3D
      landmarks were designed and acquired using a Microscribe G2X portable digitizer.
      The shape analysis software morphologika (www.york.ac.uk/res/fme) is used to
      analyze the 3D coordinates of the landmarks. A selection of multivariate
      statistics is applied to visualize the pattern, and assess the significance of,
      shape variation between the sexes and populations. The determination of sex and
      identification of population affinity are two important aspects of forensic
      investigation. Our results indicate that the adult mandible can be used to
      identify both sex and population affinity with increased sensitivity and
      objectivity compared to standard analytical techniques. 

PMID- 25868886
TI  - Unnatural death in the elderly : A forensic study from western norway.
AB  - The objective of the study was to determine the unnatural manner and causes of
      death in older people, defined as individuals at least 60 years of age at the
      time of death. A series of medico-legally examined deaths in older people, who
      were examined between January 1, 1999 and December 31, 2003, and whose deaths
      were considered unnatural after forensic examination were studied. All deaths
      took place in western Norway, in two whole counties and the north part of a third
      county, including one large Norwegian city and one medium-sized city on the west
      coast of Norway. Of the 2425 forensic examinations performed in the time period,
      1169 were 60 years or older at the time of death. Of these, 228 deaths were
      categorized as accidental, suicidal, or homicidal. Drowning was the most common
      lethal accident in elderly males, whereas fatal traffic accidents were more
      frequent in women. Alcohol intoxication was very common among male drowning
      victims, and none of the drowning victims had used a life-saving floating device.
      None of the elderly traffic victims were intoxicated. Death after a falling
      accident in the home is probably underreported. Suicide is more common among
      elderly men than women. Among men, hanging was the most common cause of death,
      whereas intoxication resultiong from drug overdose and drowning were the most
      frequent causes of death in women. Cancer was present in 19% of the suicide
      victims, all men. Serious disease may be a predisposing factor for suicidal
      behavior. Homicide is uncommon as a manner of unnatural death among the elderly. 

PMID- 25868887
TI  - The estimation of blood alcohol concentration : Widmark revisited.
AB  - Expert witnesses and others involved in toxicology are frequently asked to
      perform retrograde extrapolation of blood alcohol concentration (BAC) or to
      estimate BAC based on a proposed drinking scenario. Although many individuals are
      reluctant to perform these calculations and some jurisdictions expressly prohibit
      them, a significant number of practitioners routinely estimate BAC based on this
      type of calculation, using as a basis the fundamental work of Widmark. Although
      improvements to the Widmark formula and other data pertaining to the pharmacology
      of alcohol have been published, these improvements are frequently ignored when
      estimating BAC. This article summarizes five published models for the estimation
      of BAC and proposes a sixth model that incorporates recent data on the rate of
      absorption of alcohol from the GI tract into the existing five models. The five
      improved models can be computerized and used to construct comparative snapshots
      of the BACs calculated by the different algorithms. This will allow practitioners
      to provide a more balanced picture of the variability in BAC calculations. 

PMID- 25868888
TI  - Comparative investigation of hair with the genRES((r)) MPX-SP1, genRES MPX-SP2,
      and genRES MPX-2 kits.
AB  - In recent years there has been considerable improvement in short-tandem repeat
      (STR) investigations of hair, which were previously marred by small amounts of
      nuclear DNA and its degradation. This study examined the suitability of two STR
      kits with shortened amplicons for the investigation of hairs from routine
      casework. The overall sucess rate was more than 20%. Furthermore, the usefulness
      of quantification with real-time ploymerase chain reaction as a screening method
      was demonstrated. 

PMID- 25868889
TI  - Evaluation of suicide by hanging : From the video recording.
AB  - Most evaluations of the pathophysiological processes of suicidal hangings are
      based on animal experiments and only a few have examined the hanging process. The
      little information available is mostly the result of animal experiments that have
      focused on tracheal obstructions. In the study presented here, a camcorder was
      set up by the victim to record the entire hanging process. According to the
      analysis from the recording, the complete asphyxial process lasted only 2 minutes
      and 43 seconds. Stage 1 (the prodromal stage) was especially short. Typical
      convulsions were not observed in this case. Body movements, such as clonic and
      tonic spasms, were not noticed in stage 2 (the dyspnea stage). Because the body
      did not touch the ground, the pressure on the neck by the ligature caused
      cerebral ischemia as a result of the obstruction of the neck vessels.
      Consequently, it can be hypothesized that sui cide by hanging may not be based on
      the effect of changed concentration in the blood of carbon dioxide and oxygen,
      but on the effect of cerebral ischemia. 

PMID- 25868890
TI  - Adrenocortical carcinoma and sudden death.
AB  - A 26-year-old man who presented with a 2-year history of intermittent
      gynecomastia with recent onset of fever, night sweats, and abdominal distension
      was found to have a left-sided adrenocortical carcinoma with metastases to the
      liver and spine. Sudden death occurred 1 month after his presentation. At autopsy
      a saddle pulmonary thromboembolus was found occluding the pulmonary outflow
      tract, with smaller more peripheral pulmonary thromboemboli. No tumor deposits
      were identified in the thromboemboli. The thromboemboli had arisen from a tongue
      of tumor that had grown through the left adrenal vein into the inferior vena
      cava. Despite a high rate of angio-invasion there are very few reports of sudden
      death resulting from this phenomenon in patients with adrenocortical carcinoma. 

PMID- 25868891
TI  - Pathological findings of a fatal leopard seal attack.
AB  - A unique case of a fatal leopard seal attack against an adult human female is
      presented. The death occurred in Rothera, Antarctica when the female was
      snorkeling while undertaking scientific research. The principle injuries
      occurred, during life, to the facial areas prior to the act of drowning. The
      method of attack of leopard seals against their natural prey is discussed and
      related to the findings on the deceased. 

PMID- 25868892
TI  - Real-time PCR.
AB  - Research into the field of DNA has increased dramatically in the years since DNA
      profiling was first identified. Since then, techniques have been developed to
      identify individuals from DNA samples equivalent to a single cell. Development of
      these techniques meant that the ability to accurately quantitate the DNA in such
      samples was required to evolve at the same pace. As a result, there are a variety
      of quantitation protocols available, including the picogreen assay, slot blot
      systems, and real-time polymerase chain reaction (PCR). Real-time PCR is a
      relatively recent development but promises to be the most sensitive and accurate
      technique available. 

PMID- 25868893
TI  - The use of CT scanning in forensic autopsy.
AB  - Postmortem computed tomography (CT) is being used more frequently in forensic
      medicine. This review discusses 100 deceased individuals who underwent CT
      scanning, as well as a standard autopsy. The CT scan was performed and
      interpreted by a forensic medicine specialist. In 11 cases, important findings
      discovered during the CT scan were not found at autopsy, and in 58 cases,
      important findings revealed at autopsy were not uncovered during the CT-scan. The
      cause of death could be established by the CT scan and external examination in
      27%; by CT scan, external examination, and forensic chemistry in 32%; and by
      autopsy in 95% of the cases. CT scanning was most useful in cases of traumatic
      death. CT is rarely a substitute for autopsy, but may contribute important new
      information in cases such as identifications (particularly following mass
      disasters), battered children, gunshot wounds, traffic accidents, and air
      embolisms. CT provides documentation in digital form, which is easily stored and
      permits review by others. CT also provides pictures that may be more suitable for
      presentation in court than autopsy photos. CT scanning also would be helpful
      during a medicolegal external examination (inquest) in the process of selecting
      cases for autopsy. 

PMID- 25868894
TI  - Ba'alat.

PMID- 25868896
TI  - Exome sequencing identifies a novel intronic mutation in ENG that causes
      recurrence of pulmonary arteriovenous malformations.
AB  - Hereditary hemorrhagic telangiectasia (HHT) occasionally can be discovered in
      patients with cerebrovascular disease. Pulmonary arteriovenous malformation
      (PAVM) is one of the complications in HHT and occasionally is causative for life
      threatening embolic stroke. Several genetic defects have been reported in
      patients with HHT. The broad spectrum of phenotype and intrafamilial phenotype
      variations, including age-at-onset of vascular events, often make an early
      diagnosis difficult. We present here a Japanese family with a novel intronic
      heterozygous mutation of ENG, which was identified using whole exome sequencing
      (WES). The intronic mutation, IVS3+4delAGTG, results in in-frame deletion of exon
      3 and would produce a shorter ENG protein lacking the extracellular forty-seven
      amino acid sequences, which is located within the orphan domain. Our findings
      highlight the importance of the domain for the downstream signaling pathway of
      transforming growth factor-beta and bone morphogenesis protein superfamily
      receptors. Considering the phenotype variations and the available treatment for
      vascular complications, an early diagnosis using genetic testing, including WES,
      should be considered for individuals at risk of HHT. 

PMID- 25868895
TI  - Molecular and biochemical characterizations of a new low-temperature active
      mannanase.
AB  - A mannanase-coding gene was cloned from Sphingobacterium sp. GN25 isolated from
      the feces of Grus nigricollis. The gene encodes a 371-residue polypeptide
      (ManAGN25) showing less than 74 % identity with a number of hypothetical proteins
      and putative glucanases and mannanases. Before experiment's performance, ManAGN25
      was predicted to be a low-temperature active mannanase based on the molecular
      characterization, including (1) ManAGN25 shared the highest identity of 41.1 %
      with the experimentally verified low-temperature active mannanase (ManAJB13) from
      Sphingomonas sp. JB13; (2) compared with their mesophilic and thermophilic
      counterparts, ManAGN25 and ManAJB13 had increased number of amino acid residues
      around their catalytic sites; (3) these increased number of amino acid residues
      built longer loops, more alpha-helices, and larger total accessible surface area
      and packing volume. Then the experiments of biochemical characterization verified
      that the purified recombinant ManAGN25 is a low-temperature active mannanase: the
      enzyme showed apparently optimal activity at 35-40  degrees C and retained 78.2,
      44.8, and 15.0 % of its maximum activity when assayed at 30, 20, and 10  degrees
      C, respectively; the half-life of the enzyme was approximately 60 min at 37 
      degrees C; the enzyme presented a K m of 4.2 mg/ml and a k cat of 0.4/s in
      McIlvaine buffer (pH 7.0) at 35  degrees C using locust bean gum as the
      substrate; and the activation energy for hydrolysis of locust bean gum by the
      enzyme was 36.0 kJ/mol. This study is the first to report the molecular and
      biochemical characterizations of a mannanase from a strain. 

PMID- 25868897
TI  - Neurofilament light chain level in cerebrospinal fluid can differentiate
      Parkinson's disease from atypical parkinsonism: Evidence from a meta-analysis.
AB  - A reliable test that facilitates the accurate diagnosis of Parkinson's and
      disorders will help with both, clinical management and therapeutic research. In
      this context, neurofilament light chain (NFL) is candidate for a biomarker in
      cerebrospinal fluid (CSF). A comprehensive literature search yielded 4 eligible
      studies. We expressed between-group difference of NFL concentration in CSF as the
      standardized mean difference. Four studies involved 166 Parkinson's disease (PD),
      116 multiple system atrophy (MSA) and 73 progressive supranuclear palsy (PSP)
      patients. Patients with MSA showed higher concentration of NFL concentration in
      CSF than those with PD (standardized mean difference=1.60, P<0.0001). These
      studies were homogeneous (P=0.17). NFL in CSF in PSP was significantly elevated
      relative to PD with homogeneous studies (standardized mean difference=2.04,
      P<0.0001; P=0.99). The present meta-analysis suggested that NFL concentration in
      CSF in MSA and PSP was significantly increased relative to PD, and that this
      could help us to separate PD from atypical parkinsonian syndromes.

PMID- 25868898
TI  - Serum levels of procalcitonin and high sensitivity C-reactive protein are
      associated with long-term mortality in acute ischemic stroke.
AB  - OBJECTIVE: The aim of this study is to assess the prognostic value of systemic
      inflammation, as measured by the inflammatory biomarkers PCT and Hs-CRP, to
      predict the long-term mortality in ischemic stroke patients. METHODS: We
      prospectively studied 374 patients with ischemic stroke who were admitted within
      24h after the onset of symptoms. Serum levels of PCT, Hs-CRP and NIH stroke scale
      (NIHSS) were measured at the time of admission. Clinical follow-up was performed
      at 1 year. The prognostic value of PCT to predict the mortality within one year
      was compared with Hs-CRP, NIHSS and with other known outcome predictors. RESULTS:
      In the 64 non-survival patients, serum PCT levels were significantly (P<0.0001)
      higher compared with those in survival patients. Multivariate COX regression
      analysis showed that log-transformed PCT and Hs-CRP were independent mortality
      predictors with adjusted hazard ratio of 4.24 (95% confidence interval [CI], 2.42
      6.30) and 15.37 (95% confidence interval [CI], 3.25-41.08). The area under the
      receiver operating characteristic curve of PCT and Hs-CRP were 0.89 (95% CI, 0.85
      0.93) and 0.68 (95% CI, 0.59-0.77) for mortality, respectively. CONCLUSION: Serum
      levels of PCT and HS-CRP at admission were independent predictor of long-term
      mortality after ischemic stroke in a Chinese sample.

PMID- 25868901
TI  - Effect of chemotherapy on dietary glycemic index and load in patients with breast
      cancer and their relationships to body fat and phase angle.
AB  - Dietary glycemic index (GI) and glycemic load (GL) are indicators of carbohydrate
      consumption and widely used in studies evaluating the risk for breast cancer.
      However, the effect of chemotherapy on these indices has been scarcely studied.
      The aim of this study was to evaluate dietary levels of GI and GL in women with
      breast cancer during chemotherapy treatment and their relationships to body fat
      and phase angle. Twenty-five patients were assessed according to demographic,
      clinical, anthropometric, and food consumption data. Dietary intake was assessed
      by 24-h dietary recalls applied on nonconsecutive days. Anthropometric measures
      and body composition were determined at all study timepoints: prior to the first
      chemotherapy cycle (T0), immediately after the last chemotherapy cycle (T1), and
      2 months after T1 (T2). There was no difference in mean GI and GL among study
      timepoints. However, a high prevalence of inadequate GI and GL values was noted,
      independent of study timepoint. GI and GL were associated with phase angle at T1.
      GI was associated with percentage fat at T0 only. Dietary GI and GL were
      unchanged during chemotherapy, but were associated with indicators of clinical
      outcome, such as percentage fat and phase angle.

PMID- 25868900
TI  - Foxp1-mediated programming of limb-innervating motor neurons from mouse and human
      embryonic stem cells.
AB  - Spinal motor neurons (MNs) control diverse motor tasks including respiration,
      posture and locomotion that are disrupted by neurodegenerative diseases such as
      amyotrophic lateral sclerosis and spinal muscular atrophy. Methods directing MN
      differentiation from stem cells have been developed to enable disease modelling
      in vitro. However, most protocols produce only a limited subset of endogenous MN
      subtypes. Here we demonstrate that limb-innervating lateral motor column (LMC)
      MNs can be efficiently generated from mouse and human embryonic stem cells
      through manipulation of the transcription factor Foxp1. Foxp1-programmed MNs
      exhibit features of medial and lateral LMC MNs including expression of specific
      motor pool markers and axon guidance receptors. Importantly, they preferentially
      project axons towards limb muscle explants in vitro and distal limb muscles in
      vivo upon transplantation-hallmarks of bona fide LMC MNs. These results present
      an effective approach for generating specific MN populations from stem cells for
      studying MN development and disease. 

PMID- 25868902
TI  - Can India be successful at eradicating TB as was achieved for polio?

PMID- 25868903
TI  - A case of tuberculous peritonitis in childhood.
AB  - Currently, tuberculosis remains a major public health problem worldwide.
      Peritoneal tuberculosis occurs in approximately 1% of all of tuberculosis cases
      and is rarely observed in children. Diagnosis and treatment delays caused by
      mimicking many other intra-abdominal diseases can lead to increases in morbidity
      and mortality. Here, we present a case of a four-year-old child with tuberculosis
      peritonitis who was diagnosed by laparoscopic biopsy and histopathological
      examination and recovered with antituberculosis therapy. Peritoneal tuberculosis
      should be considered in younger patients and adults with fever, abdominal pain
      and weight loss in endemic areas. 

PMID- 25868905
TI  - GPU Assisted Simulation Study of Ion-Ion Reactions within Quadrupole Ion Traps.
AB  - In this study, a gas-phase ion-ion reaction model was developed, and it was
      integrated into an ion trajectory simulation program. GPU parallel computation
      techniques were also applied to accelerate the simulation process. With this
      simulation tool, the dependence of ion-ion reaction rate within 3D quadrupole ion
      traps on both ion trap operation parameters and the characteristics of reaction
      pair were investigated. It was found that the m/z values and charge states of
      ions have significant influences on the reaction rate. Moreover, higher ion-ion
      reaction rate was achieved under higher trapping voltages and higher buffer gas
      pressures. Furthermore, secondary reaction and/or neutralization of ETD fragment
      ions were observed from simulation. The reaction and/or neutralization rate
      depends on the charge state and m/z of each fragment ion.

PMID- 25868904
TI  - Probing Protein Structure and Folding in the Gas Phase by Electron Capture
      Dissociation.
AB  - The established methods for the study of atom-detailed protein structure in the
      condensed phases, X-ray crystallography and nuclear magnetic resonance
      spectroscopy, have recently been complemented by new techniques by which nearly
      or fully desolvated protein structures are probed in gas-phase experiments.
      Electron capture dissociation (ECD) is unique among these as it provides residue
      specific, although indirect, structural information. In this Critical Insight
      article, we discuss the development of ECD for the structural probing of gaseous
      protein ions, its potential, and limitations.

PMID- 25868906
TI  - Charge Detection Mass Spectrometry for Single Ions with an Uncertainty in the
      Charge Measurement of 0.65 e.
AB  - Charge detection mass spectrometry (CDMS) provides a direct measure of the mass
      of individual ions through nondestructive, simultaneous measurements of the mass
      to charge ratio and the charge. To improve the accuracy of the charge
      measurement, ions are trapped and recirculated through the charge detector. By
      substantially extending the trapping time, the uncertainty in the charge
      determination has been reduced by a factor of two, from 1.3 elementary charges
      (e) to 0.65 e. The limit of detection (the smallest charge that can be reliably
      measured) has been reduced by about the same proportion, from 13 to 7 e. The more
      precise charge measurements enable a substantial improvement in the mass
      resolution, which is critical for applications of CDMS to mixtures of high mass
      ions.

PMID- 25868907
TI  - Identification of a transformer homolog in the acorn worm, Saccoglossus
      kowalevskii, and analysis of its activity in insect cells.
AB  - The transformer (tra) gene is an intermediate component of the sex determination
      hierarchy in many insect species. The homolog of tra is also found in two
      branchiopod crustacean species but is not known outside arthropods. We have
      isolated a tra homolog in the acorn worm, Saccoglossus kowalevskii, which is a
      hemichordate belonging to the deuterostome superphylum. The full-length
      complementary DNA (cDNA) of the S. kowalevskii tra homolog (Sktra) has a 3786-bp
      open reading frame that encodes a 1261-amino acid sequence including a TRA-CAM
      domain and an arginine/serine (RS)-rich domain, both of which are characteristic
      of TRA orthologs. Reverse transcription PCR (RT-PCR) analyses demonstrated that
      Sktra showed no differences in expression patterns between testes and ovaries,
      but its expression level was approximately 7.5-fold higher in the testes than in
      the ovaries. TRA, together with the protein product of the transformer-2 (tra-2)
      gene, assembles on doublesex (dsx) pre-messenger RNA (mRNA) via the cis
      regulatory element, enhancing female-specific splicing of dsx in Drosophila. To
      understand functional conservation of the SkTRA protein as a dsx-splicing
      activator, we investigated whether SkTRA is capable of inducing female-specific
      splicing of the Drosophila dsx. Ectopic expression of Sktra cDNA in insect
      cultured cells did not induce the female-specific splicing of dsx. On the other
      hand, forced expression of Sktra-2 (a tra-2 homolog of S. kowalevskii) was able
      to induce the female-specific dsx splicing. These results demonstrate that the
      function as a dsx-splicing activator is not conserved in SkTRA even though SkTRA
      2 is capable of functionally replacing the Drosophila TRA-2. We have also found a
      tra homolog in an echinoderm genome. This study provides the first evidence that
      that tra is conserved not only in arthropods but also in basal species of
      deuterostoms. 

PMID- 25868908
TI  - A method for immunolabeling neurons in intact cuticularized insect appendages.
AB  - The antennae of the grasshopper Schistocerca gregaria possess a pair of nerve
      pathways which are established by so-called pioneer neurons early in embryonic
      development. Subsequently, sensory cell clusters mediating olfaction, flight,
      optomotor responses, and phase changes differentiate from the antennal epithelium
      at stereotypic locations and direct their axons onto those of the pioneers to
      then project to the brain. Early in embryonic development, before the antennae
      become cuticularized, immunolabeling can be used to follow axogenesis in these
      pioneers and sensory cells. At later stages, immunolabeling becomes problematical
      as the cuticle is laid down and masks internal antigen sites. In order to
      immunolabel the nervous system of cuticularized late embryonic and first instar
      grasshopper antennae, we modified a procedure known as sonication in which the
      appendage is exposed to ultrasound thereby rendering it porous to antibodies.
      Comparisons of the immunolabeled nervous system of sectioned and sonicated
      antennae show that the cellular organization of sensory clusters and their axon
      projections is intact. The expression patterns of neuron-specific, microtubule
      specific, and proliferative cell-specific labels in treated antennae are
      consistent with those reported for earlier developmental stages where sonication
      is not necessary, suggesting that these molecular epitopes are also conserved.
      The method ensures reliable immunolabeling in intact, cuticularized appendages so
      that the peripheral nervous system can be reconstructed directly via confocal
      microscopy throughout development. 

PMID- 25868909
TI  - The burrowing behavior of the nematode Caenorhabditis elegans: a new assay for
      the study of neuromuscular disorders.
AB  - The nematode Caenorhabditis elegans has been a powerful model system for the
      study of key muscle genes relevant to human neuromuscular function and disorders.
      The behavioral robustness of C. elegans, however, has hindered its use in the
      study of certain neuromuscular disorders because many worm models of human
      disease show only subtle phenotypes while crawling. By contrast, in their natural
      habitat, C. elegans likely spends much of the time burrowing through the soil
      matrix. We developed a burrowing assay to challenge motor output by placing worms
      in agar-filled pipettes of increasing densities. We find that burrowing involves
      distinct kinematics and turning strategies from crawling that vary with the
      properties of the substrate. We show that mutants mimicking Duchenne muscular
      dystrophy by lacking a functional ortholog of the dystrophin protein, DYS-1,
      crawl normally but are severely impaired in burrowing. Muscular degeneration in
      the dys-1 mutant is hastened and exacerbated by burrowing, while wild type shows
      no such damage. To test whether neuromuscular integrity might be compensated
      genetically in the dys-1 mutant, we performed a genetic screen and isolated
      several suppressor mutants with proficient burrowing in a dys-1 mutant
      background. Further study of burrowing in C. elegans will enhance the study of
      diseases affecting neuromuscular integrity, and will provide insights into the
      natural behavior of this and other nematodes. 

PMID- 25868910
TI  - Antiplatelet drug resistance: Molecular insights and clinical implications.
AB  - Antiplatelet drugs are prescribed to patients with cardiovascular disease in
      order to reduce their risk of clinically important atherothrombotic events.
      However, a proportion of patients fail to appropriately respond to these drugs in
      a heterogeneous phenomenon known as 'antiplatelet drug resistance'. Individuals
      who are identified as being resistant have a higher cardiovascular risk, but
      currently there is no clinically validated approach to identify and treat these
      individuals. Large randomised control trials have attempted to personalise
      antiplatelet therapy based on platelet function testing, but these have failed to
      demonstrate improved clinical outcomes. An alternative approach to this non
      specific assessment of platelet function is to consider whether antiplatelet
      therapy may be personalised based on the identification of molecular mechanisms
      that are known to confer resistance. Here we present molecular insights into the
      mechanisms for aspirin and clopidogrel resistance, with a discussion of their
      clinical implications. 

PMID- 25868911
TI  - Induction of CD4(+) and CD8(+) anti-tumor effector T cell responses by bacteria
      mediated tumor therapy.
AB  - Facultative anaerobic bacteria like E. coli can colonize solid tumors often
      resulting in tumor growth retardation or even clearance. Little mechanistic
      knowledge is available for this phenomenon which is however crucial for
      optimization and further implementation in the clinic. Here, we show that
      intravenous injections with E. coli TOP10 can induce clearance of CT26 tumors in
      BALB/c mice. Importantly, re-challenging mice which had cleared tumors showed
      that clearance was due to a specific immune reaction. Accordingly, lymphopenic
      mice never showed tumor clearance after infection. Depletion experiments revealed
      that during induction phase, CD8(+) T cells are the sole effectors responsible
      for tumor clearance while in the memory phase CD8(+) and CD4(+) T cells were
      involved. This was confirmed by adoptive transfer. CD4(+) and CD8(+) T cells
      could reject newly set tumors while CD8(+) T cells could even reject established
      tumors. Detailed analysis of adoptively transferred CD4(+) T cells during tumor
      challenge revealed expression of granzyme B, FasL, TNF-alpha and IFN-gamma in
      such T cells that might be involved in the anti-tumor activity. Our findings
      should pave the way for further optimization steps of this promising therapy. 

PMID- 25868912
TI  - Genomic and phenotypic analyses of Carnobacterium jeotgali strain MS3(T), a
      lactate-producing candidate biopreservative bacterium isolated from salt
      fermented shrimp.
AB  - Carnobacterium jeotgali strain MS3(T) was isolated from traditionally fermented
      Korean shrimp produced with bay salt. The bacterium belongs to the family
      Carnobacteriaceae, produces lactic acid and contains gene clusters involved in
      the production of lactate, butyrate, aromatic compounds and exopolysaccharides.
      Carnobacterium jeotgali strain MS3(T) was characterized through extensive
      comparison of the virulence potential, genomic relatedness and sequence
      similarities of its genome with the genomes of other Carnobacteria and lactic
      acid bacteria. In addition, links between predicted functions of genes and
      phenotypic characteristics, such as antibiotic resistance and lactate and
      butyrate production, were extensively evaluated. Genomic and phenotypic analyses
      of strain MS3(T) revealed promising features, including minimal virulence genes
      and lactate production, which make this bacterium a desirable candidate for
      exploitation by the fermented food industry. 

PMID- 25868913
TI  - Untargeted metabolic profiling of Vitis vinifera during fungal degradation.
AB  - This paper illustrates the application of an untargeted metabolic profiling
      analysis of winery-derived biomass degraded using four filamentous fungi
      (Trichoderma harzianum, Aspergillus niger, Penicillium chrysogenum and P.
      citrinum) and a yeast (Saccharomyces cerevisiae). Analysis of the metabolome
      resulted in the identification of 233 significant peak features [P < 0.05; fold
      change (FC) > 2 and signal-to-noise ratio >50] using gas chromatography-mass
      spectrometry followed by statistical chemometric analysis. Furthermore, A. niger
      and P. chrysogenum produced higher biomass degradation due to considerable beta
      glucosidase and xylanase activities. The major metabolites generated during
      fungal degradation which differentiated the metabolic profiles of fungi included
      sugars, sugar acids, organic acids and fatty acids. Although, P. chrysogenum
      could degrade hemicelluloses due to its high beta-glucosidase and xylanase
      activities, it could not utilize the resultant pentoses, which A. niger and P.
      citrinum could do efficiently, thus indicating a need of mixed fungal culture to
      improve the biomass degradation. Saccharomyces cerevisiae, a non-cellulose
      degrader, exhibited sugar accumulation during the fermentation. Penicillium
      chrysogenum was observed to degrade about 2% lignin, a property not observed in
      other fungi. This study emphasized the differential fungal metabolic behavior and
      demonstrated the potential of metabolomics in optimizing degradation or
      manipulating pathways to increase yields of products of interest.

PMID- 25868914
TI  - Endocytosis of GABA(C) receptors depends on subunit composition and is regulated
      by protein kinase C-zeta and protein phosphatase 1.
AB  - Neuronal excitability depends on the surface concentration of neurotransmitter
      receptors. Type C gamma-aminobutyric acid receptors (GABA(C)R) are composed of
      rho subunits that are highly expressed in the retina. Molecular mechanisms that
      guide the surface concentration of this receptor type are largely unknown.
      Previously, we reported physical interactions of GABA(C)R rho subunits with
      protein kinase C-zeta (PKCzeta) via adapter proteins of the ZIP protein family,
      as well as of protein phosphatase 1 (PP1) via PNUTS. Here, we demonstrate that co
      expressing rho1 with ZIP3 and PKCzeta enhanced basal internalization of GABA(C)R,
      while receptor internalization was reduced in the presence of PNUTS and PP1. Co
      expression of rho1 with individual binding partners showed no alterations, except
      for PP1. Heterooligomeric GABA(C)R composed of rho1 and rho2 subunits had a
      significant higher endocytosis rate than rho1 containing homooligomeric
      receptors. Mutant constructs lacking binding sites for protein interactions
      ensured the specificity of our data. Finally, substitution of serine and
      threonine residues with alanines indicated that GABA(C)R internalization depends
      on serine/threonine kinases and phosphatases, but not on tyrosine
      phosphorylation. We conclude that GABA(C)R internalization is reciprocally
      regulated by PKCzeta and PP1 that are anchored to the receptor via ZIP3 or PNUTS
      respectively.

PMID- 25868916
TI  - The relationship between perceived parenting styles and resilience during
      adolescence.
AB  - Objective - The aim of this research was to investigate the relationship between
      perceived parenting styles and resilience in adolescence. Method - The
      respondents were a sample of 360 English speaking subjects, with a mean age of
      17.6 years. Hierarchical regression analyses were used to investigate this
      relationship. The criterion variables included sense of coherence and problem
      focused, emotion-focused and dysfunctional coping strategies. The predictor
      variables included six scales. Results - Authoritative parenting provided the
      most significant contribution to the explanation of the variance in resilience
      for black and white adolescents, and both genders. Surprisingly, the findings
      suggest that there is a positive relationship between fathers' authoritarian
      styles and emotion-focused coping strategies in white adolescent learners. In
      contrast, other researchers found that authoritarian and harsh parental styles
      are closely related to psychological disturbance. Conclusions - The identified
      relationships between the criterion and predictor variables found in this study
      for both black and white adolescents of both genders have distinct and far
      reaching implications for envisaged interventions. A future study might also
      investigate the present study qualitatively. Further research will be necessary
      to enhance and develop appropriate parenting styles that facilitate resilience in
      adolescent children. Making use of more sophisticated methodologies, paying
      greater attention to the interaction between internal and external circumstances
      and refining theories to make specific predictions about how input variables
      influence components, should be considered in future. 

PMID- 25868915
TI  - Evaluation of an optimized protocol using human peripheral blood monocyte derived
      dendritic cells for the in vitro detection of sensitizers: Results of a ring
      study in five laboratories.
AB  - Allergic contact dermatitis is a delayed T-cell mediated allergic response
      associated with relevant social and economic impacts. Animal experiments (e.g.
      the local lymph node assay) are still supplying most of the data used to assess
      the sensitization potential of new chemicals. However, the 7th amendment to the
      EU Cosmetic Directive have introduced a testing ban for cosmetic ingredients
      after March 2013. We have developed and optimized a stable and reproducible in
      vitro protocol based on human peripheral blood monocyte derived dendritic cells
      to assess the sensitization potential of chemicals. To evaluate the
      transferability and the predictivity of this PBMDCs based test protocol, a ring
      study was organized with five laboratories using seven chemicals with a known
      sensitization potential (one none-sensitizer and six sensitizers, including one
      pro-hapten). The results indicated that this optimized test protocol could be
      successfully transferred to all participating laboratories and allowed a correct
      assessment of the sensitization potential of the tested set of chemicals. This
      should allow a wider acceptance of PBMDCs as a reliable test system for the
      detection of human skin sensitizers and the inclusion of this protocol in the
      toolbox of in vitro methods for the evaluation of the skin sensitization
      potential of chemicals. 

PMID- 25868917
TI  - Educators' views on the needs and support of HIV/AIDS orphans in their
      psychosocial development.
AB  - Objective - Educators' perceptions of the psychosocial needs of HIV/AIDS orphans
      are important in supporting these children. The objective of this research is to
      determine the view of educators regarding the psychosocial needs of HIV/AIDS
      affected children. Method - A questionnaire, based on a thorough literature study
      was administered to determine the views of teachers. A convenient sample of 120
      teachers from different schools, who attended a workshop organised for the
      primary schools in a particular school district in Tswane was used. Results -
      Only about half of the educators indicated that their schools provided support
      for HIV/AIDS orphans. Lack of food and clothing were viewed as the most pressing
      physical needs of the orphans. The desire for security, acceptance, dealing with
      stress, managing fears and psychological support services were identified as
      important psychological needs. Lack of security was seen as the most important
      factor affecting the psychosocial behaviour of these learners. Depression,
      sadness and stigmatisation were viewed as primary influences on behaviour.
      Teaching position, gender and age significantly influenced educators' views of
      various aspects of the learners' needs and behaviours. Conclusion - These
      findings have important implications for the training of educators to support
      learners and caregivers of children affected by the disease. 

PMID- 25868918
TI  - Sexual abuse of boys in KwaZulu-Natal, South Africa: a hospital-based study.
AB  - Objective - The aim of the study was to determine the prevalence and factors
      associated with child sexual abuse in a total sample of boys referred for medico
      legal assessment in a peri-urban area of KwaZulu-Natal, South Africa. Method - A
      retrospective analysis was undertaken of clinical and social work records for
      sexually abused boys presenting for medico-legal assessment at the Mahatma Gandhi
      Memorial Hospital (Phoenix, KwaZulu-Natal) during the period January 2001 to
      December 2003. Results - In the period reviewed, 131 boys reported an incident of
      sexual abuse with temporal trends indicating a significant increase in the
      incidence of reported abuse over the three year period. Most victims fell in the
      4-11 year age category, anal penetration constituted the most common form of
      abuse (86% of cases), and perpetrators were predominantly persons who were known
      to the child. Conclusion - Study findings indicate that the sexual abuse of boys
      constitutes a sizeable and emerging problem in peri-urban communities in South
      Africa. Evidence suggests that increased rates of victimisation are associated
      with a breakdown in family support networks in the context of rapid urbanisation.

PMID- 25868919
TI  - A comparative study of behaviour problems between adopted and nonadopted children
      in India.
AB  - A review of existing literature concludes that there is an increased risk for the
      development of behaviour problems among adopted children compared to non-adopted
      children. This study was conducted with the objective of finding out whether the
      findings are consistent within the Indian context, which offers a different
      psycho-cultural setting to most western settings in which the previous studies
      were carried out. We compared groups of adopted children and non-adopted children
      on various parameters i.e. Parent Symptom Questionnaire (PSQ), ADHD rating scale,
      Alabama Parenting Questionnaire and the Social Adjustment Inventory for Children
      and Adolescents (SAICA). The Malin's intelligence scale for Indian children
      (MISIC) was administered to the children for assessing IQ while the Diagnostic
      and Statistical Manual (DSM-IV) was used to diagnose psychopathology. We found
      that adopted children had more behaviour problems on the PSQ. On SAICA, adopted
      children showed less social competence. The parenting practices as revealed by
      the Alabama Parenting Questionnaire did not differ between the two groups. The IQ
      of the children in both groups was within the normal range. We concluded that the
      psycho-social consequences of adoption in India do not differ from those of other
      countries, all of which show a higher incidence of behaviour problems in adopted
      children. 

PMID- 25868920
TI  - The Effect of Parent Management Training on children with attention deficit
      hyperactivity disorder.
AB  - Objective - To investigate the effect of Parent Management Training (PMT) on
      behaviour of children diagnosed with attention deficit hyperactivity disorder
      (ADHD) and the general mental health of their parents. Method - Twelve parents
      whose children or adolescents were diagnosed with ADHD agreed to participate in
      the PMT classes for eight weekly sessions of 11/2 hours duration. The children
      were aged between 4 and 13 years. The general mental health of parents and the
      behaviour of their children were assessed at the first, and after the last
      training sessions on measures of General Mental Health Questionnaire (GHQ-28),
      Conners' Parent Rating Scale-Revised (CPRS-R), and Conners' Teacher Rating Scale
      Revised (CTRS-R). Results - The total score of CPRS-R, and the subscale scores
      measuring conduct problems, learning problems and the hyperactivity index all
      decreased significantly. None of the scores on the CTRS-R changed significantly.
      The mean scores of the GHQ-28 were significant less after the intervention
      compared to before the intervention. Conclusion - PMT improved the behaviour of
      the children with ADHD and the general mental health of the parents. It is
      possible that the high refusal rate is an indication that the intervention may be
      unacceptable to a large proportion of parents. 

PMID- 25868922
TI  - Munchausen by proxy: identification, intervention and case management by louisa
      j. Lasher and Mary s. Sheridan.

PMID- 25868921
TI  - Sexual behaviour of Nigerian university students.
AB  - Objective - The objective of this study was to document selected aspects of the
      sexuality of Nigerian university students, specifically sexual behaviour,
      attitudes about sexuality, the circumstances of sexual intercourse and preventive
      sexual behaviour. Method - A total of 1 153 students at two federal universities
      in Nigeria completed a self administered questionnaire. Results - The mean age of
      first intercourse was 17.0 years for males and 19.1 years for females. Male
      students were more likely to have had sex and to engage in unsafe sex. There were
      no obvious differences between the genders in the numbers of same-sex partners.
      Levels of sexual activity were high. For example, 53.8% had experienced
      intercourse, and 24.4% reported more than one regular sex partner. Male students
      displayed more permissive attitudes than female students. A minority reported
      having the same sexual attitudes as their parents or friends, and discussing
      their sex lives with their parents. A substantial proportion of the students
      believed that if you loved a partner you could not ask him/her to use condom
      while having sex. Condoms were the most commonly reported preventive method that
      was used. The majority of both male and female students reported that they
      'always' or 'often' used protection when having sex. Conclusions - There is a
      need to begin to address emerging reproductive health issues in Nigerian tertiary
      institutions. Data regarding attitudes about sexuality and circumstances of
      intercourse can inform the content of intervention programmes. 

PMID- 25868923
TI  - "Letting them Die": How HIV/AIDS prevention programmes often fail by Catherine
      Campbell.

PMID- 25868925
TI  - The link between childhood trauma and mental illness: effective interventions for
      mental health professionals by barbara everett and ruth gallop.

PMID- 25868924
TI  - Why Love Matters. How Affection Shapes a Baby's Brain by Sue Gerhardt.

PMID- 25868926
TI  - Blackwell Handbook of Infant Development (edited by Gavin Bremner and Alan
      Fogel).

PMID- 25868927
TI  - Journal abstracts from current research in the field of child and adolescent
      mental health.

PMID- 25868928
TI  - How prepared are we to help children cope in the aftermath of a national
      disaster?

PMID- 25868929
TI  - Sustained attention abnormalities in breast cancer survivors with cognitive
      deficits post chemotherapy: An electrophysiological study.
AB  - OBJECTIVE: Many breast cancer survivors (BCS) report cognitive problems following
      chemotherapy, yet controversy remains concerning which cognitive domains are
      affected. This study investigated a domain crucial to daily function: the ability
      to maintain attention over time. METHODS: We examined whether BCS who self
      reported cognitive problems up to 3 years following cancer treatment (n=19)
      performed differently from healthy controls (HC, n=12) in a task that required
      sustained attention. Participants performed a target detection task while
      periodically being asked to report their attentional state. Electroencephalogram
      was recorded during this task and at rest. RESULTS: BCS were less likely to
      maintain sustained attention during the task compared to HC. Further, the P3
      event-related potential component elicited by visual targets during the task was
      smaller in BCS relative to HC. BCS also displayed greater neural activity at
      rest. CONCLUSIONS: BCS demonstrated an abnormal pattern of sustained attention
      and resource allocation compared to HC, suggesting that attentional deficits can
      be objectively observed in breast cancer survivors who self-report concentration
      problems. SIGNIFICANCE: These data underscore the value of EEG combined with a
      less traditional measure of sustained attention, or attentional states, as
      objective laboratory tools that are sensitive to subjective complaints of
      chemotherapy-related attentional impairments.

PMID- 25868930
TI  - Psychotic experiences in the population: Association with functioning and mental
      distress.
AB  - Psychotic experiences are far more common in the population than psychotic
      disorder. They are associated with a number of adverse outcomes but there has
      been little research on associations with functioning and distress. We wished to
      investigate functioning and distress in a community sample of adolescents with
      psychotic experiences. Two hundred and twelve school-going adolescents were
      assessed for psychotic experiences, mental distress associated with these
      experiences, global (social/occupational) functioning on the Children's Global
      Assessment Scale, and a number of candidate mediator variables, including
      psychopathology, suicidality, trauma (physical and sexual abuse and exposure to
      domestic violence) and neurocognitive functioning. Seventy five percent of
      participants who reported psychotic experiences reported that they found these
      experiences distressing (mean score for severity of distress was 6.9 out of
      maximum 10). Participants who reported psychotic experiences had poorer
      functioning than participants who did not report psychotic experiences
      (respective means: 68.6, 81.9; OR=0.25, 95% CI=0.14-0.44). Similarly,
      participants with an Axis-1 psychiatric disorder who reported psychotic
      experiences had poorer functioning than participants with a disorder who did not
      report psychotic experiences (respective means: 61.8, 74.5; OR=0.28, 95% CI=0.12
      0.63). Candidate mediator variables explained some but not all of the
      relationship between psychotic experiences and functioning (OR=0.48, 95% CI=0.22
      1.05, P<0.07). Young people with psychotic experiences have poorer global
      functioning than those who do not, even when compared with other young people
      with psychopathology (but who do not report psychotic experiences). A disclosure
      of psychotic experiences should alert treating clinicians that the individual may
      have significantly more functional disability than suggested by the
      psychopathological diagnosis alone. 

PMID- 25868931
TI  - NMDAR hypofunction attenuates driver inputs in higher order thalamic nuclei: an
      alternative view.

PMID- 25868932
TI  - Childhood adversity specificity and dose-response effect in non-affective first
      episode psychosis.
AB  - BACKGROUND: Reviews conclude that childhood and adolescence sexual, physical,
      emotional abuse and emotional and physical neglect are all risk factors for
      psychosis. However, studies suggest only some adversities are associated with
      psychosis. Dose-response effects of several adversities on risk of psychosis have
      not been consistently found. The current study aimed to explore adversity
      specificity and dose-response effects of adversities on risk of psychosis.
      METHOD: Participants were 101 persons with first-episode psychosis (FEP)
      diagnosed with ICD-10 F20 - F29 (except F21) and 101 non-clinical control persons
      matched by gender, age and parents' socio-economic status. Assessment included
      the Childhood Trauma Questionnaire and parts of the Childhood Experience of Care
      and Abuse Questionnaire. RESULTS: Eighty-nine percent of the FEP group reported
      one or more adversities compared to 37% of the control group. Childhood and
      adolescent sexual, physical, emotional abuse, and physical and emotional neglect,
      separation and institutionalization were about four to 17 times higher for the
      FEP group (all p<0.01). The risk of psychosis increased two and a half times for
      each additional adversity. All associations between specific adversities and
      psychosis decreased when they were adjusted for other adversities. CONCLUSION:
      Our findings suggest that there is a large shared effect of adversities on the
      risk of psychosis. Contrary to the call for further research into specific
      adversities, we suggest a search for mechanisms in the shared effects of
      traumatization. Clinical implications are thorough assessment of adversities and
      their possible effects.

PMID- 25868933
TI  - Left-hemisphere lateralization for language and interhemispheric fiber tracking
      in patients with schizophrenia.
AB  - BACKGROUND: It has been suggested that the degree of hemispheric specialization
      (HS) depends on the structural connectivity between the two hemispheres, that is
      to say the corpus callosum (CC). Studies, performed only on healthy participants,
      investigated this anatomo-functional relationship. Nevertheless, it has never
      been studied in schizophrenia. We therefore propose to study the anatomo
      functional relationships between the integrity of interhemispheric connectivity
      and leftward functional lateralization for language in patients with
      schizophrenia compared with healthy participants, driven by a multimodal approach
      combining fMRI and DTI-based fiber tractography. We hypothesized that reduced
      leftward functional lateralization for language in patients with schizophrenia
      could be related to a callosal hypoconnectivity. MATERIALS AND METHODS: Seventeen
      patients based on the DSM-IV, and 17 controls were included. The functional
      laterality index and interhemispheric diffusion values between homologue temporal
      regions, belonging to the language network, were individually extracted in order
      to study the anatomo-functional relationships. RESULTS: In the patients, higher
      mean and radial diffusivity (RD) values (thicker myelin sheaths) were associated
      with less leftward lateralization. In contrast, the controls presented higher RD
      values and lower fractional anisotropy values (axonal loss) with more leftward
      lateralization. CONCLUSIONS: Our study revealed a relationship between the CC and
      the HS for language, but did not provide evidence clarifying the direction of the
      relationship between callosal connectivity and functional lateralization for
      language. In particular, the present findings showed that the loss of integrity
      in interhemispheric callosal fibers was associated with reduced leftward cerebral
      dominance for language in patients with schizophrenia.

PMID- 25868934
TI  - Patterns of cannabis use, psychotic-like experiences and personality styles in
      young cannabis users.
AB  - OBJECTIVE: To examine the influence of personality traits on the relationship
      between cannabis use and psychotic like experiences (PLEs) in young adults.
      METHOD: 499 lifetime cannabis users aged 18 to 25years completed an online survey
      assessing PLEs using the positive scale of the Community Assessment of Psychic
      Experiences (CAPE) and personality styles using the Brief Schizotypal Personality
      Questionnaire (SPQ-B) and the Substance Use Risk Profile Scale (SURPS), a measure
      of trait hopelessness, anxiety-sensitivity, impulsivity and sensation seeking.
      Cannabis use was assessed using items from the Youth Risk Behaviour Survey (YRBS)
      and a self-report measure of the lifetime level of cumulative cannabis use.
      RESULTS: Cannabis use as well as schizotypy and the four SURPS personality risk
      profiles were significantly associated with the frequency of PLEs in young
      cannabis users. The cumulative levels of lifetime cannabis exposure, trait
      schizotypy and hopelessness were the strongest predictors of PLEs in the
      multivariate analysis. Little evidence of a moderating effect of the personality
      risk profiles on the relationship between cannabis use and PLEs was found. Trait
      hopelessness was found to have a moderating effect on the relationship between
      the recency of cannabis use and the frequency of PLEs. CONCLUSIONS: The
      cumulative levels of lifetime cannabis exposure, trait schizotypy and
      hopelessness were associated with PLEs in young cannabis users. Individuals with
      high levels of trait hopelessness who use cannabis may be at higher risk of PLEs.
      Future research is required to increase understanding of the relationship between
      cannabis use and PLEs, using more complex moderation models containing
      personality traits along with other risk factors for PLEs.

PMID- 25868935
TI  - Determinants of different aspects of everyday outcome in schizophrenia: The roles
      of negative symptoms, cognition, and functional capacity.
AB  - Cognition, negative symptoms, and depression are potential predictors of
      disability in schizophrenia. We present analyses of pooled data from four
      separate studies (all n>169; total n=821) that assessed differential aspects of
      disability and their potential determinants. We hypothesized that negative
      symptoms would predict social outcomes, but not vocational functioning or
      everyday activities and that cognition and functional capacity would predict
      vocational functioning and everyday activities but not social outcomes. The
      samples were rated by clinician informants for their everyday functioning in
      domains of social and vocational outcomes, and everyday activities, examined with
      assessments of cognition and functional capacity, rated clinically with the
      Positive and Negative Syndrome Scale (PANSS) and self-reporting depression. We
      computed a model that tested the hypotheses described above and compared it to a
      model that predicted that negative symptoms, depression, cognition, and
      functional capacity had equivalent influences on all aspects of everyday
      functioning. The former, specific relationship model fit the data adequately and
      we subsequently confirmed a similar fit within all four samples. Analyses of the
      relative goodness of fit suggested that this specific model fit the data better
      than the more general, equivalent influence predictor model. We suggest that
      treatments aimed at cognition may not affect social functioning as much as other
      aspects of disability, a finding consistent with earlier research on the
      treatment of cognitive deficits in schizophrenia, while negative symptoms
      predicted social functioning. These relationships are central features of
      schizophrenia and treatment efforts should be aimed accordingly. 

PMID- 25868937
TI  - Sampling the upper respiratory tract for enteroviral infection is important in
      the investigation of an acute neurological illness in children.

PMID- 25868936
TI  - Stimulus train duration but not attention moderates gamma-band entrainment
      abnormalities in schizophrenia.
AB  - Electroencephalographic (EEG) studies of auditory steady-state responses (aSSRs)
      non-invasively probe gamma-band (40-Hz) oscillatory capacity in sensory cortex
      with high signal-to-noise ratio. Consistent reports of reduced 40-Hz aSSRs in
      persons with schizophrenia (SZ) indicate its potential as an efficient biomarker
      for the disease, but studies have been limited to passive or indirect listening
      contexts with stereotypically short (500ms) stimulus trains. An inability to
      modulate sensorineural processing in accord with behavioral goals or within the
      sensory environmental context may represent a fundamental deficit in SZ, but
      whether and how this deficit relates to reduced aSSRs is unknown. We
      systematically varied stimulus duration and attentional contexts to further
      mature the 40-Hz aSSR as biomarker for future translational or mechanistic
      studies. Eighteen SZ and 18 healthy subjects (H) were presented binaural pure
      tones with or without sinusoidal amplitude modulation at 40-Hz. Stimulus duration
      (500-ms or 1500-ms) and attention (via a button press task) were varied across 4
      separate blocks. Evoked potentials recorded with dense-array EEGs were analyzed
      in the time-frequency domain. SZ displayed reduced 40-Hz aSSRs to typical
      stimulation parameters, replicating previous findings. In H, aSSRs were reduced
      when stimuli were presented in longer trains and were slightly enhanced by
      attention. Only the former modulation was impaired in SZ and correlated with
      sensory discrimination performance. Thus, gamma-band aSSRs are modulated by both
      attentional and stimulus duration contexts, but only modulations related to
      physical stimulus properties are abnormal in SZ, supporting its status as a
      biomarker of psychotic perceptual disturbance involving non-attentional sensori
      cortical circuits. 

PMID- 25868938
TI  - Achilles tendon rupture rehabilitation: a mixed methods investigation of current
      practice among orthopaedic surgeons in the United Kingdom.
AB  - OBJECTIVES: The evidence base to inform the management of Achilles tendon rupture
      is sparse. The objectives of this research were to establish what current
      practice is in the United Kingdom and explore clinicians' views on proposed
      further research in this area. This study was registered with the ISRCTN
      (ISRCTN68273773) as part of a larger programme of research. METHODS: We report an
      online survey of current practice in the United Kingdom, approved by the British
      Orthopaedic Foot and Ankle Society and completed by 181 of its members. A total
      of ten of these respondents were invited for a subsequent one-to-one interview to
      explore clinician views on proposed further research in this area. RESULTS: The
      survey showed wide variations in practice, with patients being managed in plaster
      cast alone (13%), plaster cast followed by orthoses management (68%), and
      orthoses alone (19%). Within these categories, further variation existed
      regarding the individual rehabilitation facets, such as the length of time worn,
      the foot position within them and weight-bearing status. The subsequent
      interviews reflected this clinical uncertainty and the pressing need for
      definitive research. CONCLUSIONS: The gap in evidence in this area has resulted
      in practice in the United Kingdom becoming varied and based on individual
      opinion. Future high-quality randomised trials on this subject are supported by
      the clinical community. Cite this article: Bone Joint Res 2015;4:65-9.

PMID- 25868939
TI  - Robust patterning of gene expression based on internal coordinate system of
      cells.
AB  - Cell-to-cell communication in multicellular organisms is established through the
      transmission of various kinds of chemical substances such as proteins. It is well
      known that gene expression triggered by a chemical substance in individuals has
      stable spatial patterns despite the individual differences in concentration
      patterns of the chemical substance. This fact reveals an important property of
      multicellular organisms called "robustness", which allows the organisms to
      generate their forms while maintaining proportion. Robustness has been
      conventionally accounted for by the stability of solutions of dynamical equations
      that represent a specific interaction network of chemical substances. However,
      any biological system is composed of autonomous elements. In general, an
      autonomous element does not merely accept information on the chemical substance
      from the environment; instead, it accepts the information based on its own
      criteria for reaction. Therefore, this phenomenon needs to be considered from the
      viewpoint of cells. Such a viewpoint is expected to allow the consideration of
      the autonomy of cells in multicellular organisms. This study aims to explain
      theoretically the robust patterning of gene expression from the viewpoint of
      cells. For this purpose, we introduced a new operator for transforming a state
      variable of a chemical substance from an external coordinate system to an
      internal coordinate system of each cell, which describes the observation of the
      chemical substance by cells. We then applied this operator to the simplest
      reaction-diffusion model of the chemical substance to investigate observation
      effects by cells. Our mathematical analysis of this extended model indicates that
      the robust patterning of gene expression against individual differences in
      concentration pattern of the chemical substance can be explained from the
      viewpoint of cells if there is a regulation field that compensates for the
      difference between cells seen in the observation results. This result provides a
      new insight into the investigation of the mechanism of robust patterning in
      biological systems composed of individual elements. 

PMID- 25868940
TI  - Cheating is evolutionarily assimilated with cooperation in the continuous
      snowdrift game.
AB  - It is well known that in contrast to the Prisoner's Dilemma, the snowdrift game
      can lead to a stable coexistence of cooperators and cheaters. Recent theoretical
      evidence on the snowdrift game suggests that gradual evolution for individuals
      choosing to contribute in continuous degrees can result in the social
      diversification to a 100% contribution and 0% contribution through so-called
      evolutionary branching. Until now, however, game-theoretical studies have shed
      little light on the evolutionary dynamics and consequences of the loss of
      diversity in strategy. Here, we analyze continuous snowdrift games with quadratic
      payoff functions in dimorphic populations. Subsequently, conditions are clarified
      under which gradual evolution can lead a population consisting of those with 100%
      contribution and those with 0% contribution to merge into one species with an
      intermediate contribution level. The key finding is that the continuous snowdrift
      game is more likely to lead to assimilation of different cooperation levels
      rather than maintenance of diversity. Importantly, this implies that allowing the
      gradual evolution of cooperative behavior can facilitate social inequity aversion
      in joint ventures that otherwise could cause conflicts that are based on commonly
      accepted notions of fairness. 

PMID- 25868941
TI  - The impact of pharmaceutical care interventions for medication underuse in older
      people: a systematic review and meta-analysis.
AB  - AIMS: The aim of the present study was to conduct a meta-analysis of controlled
      trials assessing the impact of pharmaceutical care interventions (e.g. medication
      reviews) on medication underuse in older patients (>=65 years). METHODS: The
      databases MEDLINE and EMBASE were searched for controlled studies, and data on
      interventions, patient characteristics and exposure, and outcome assessment were
      extracted. Risk of bias was assessed using the Cochrane Collaboration's 'risk of
      bias' table. Results from reported outcomes were synthesized in multivariate
      random effects meta-analysis, subgroup meta-analysis and meta-regression.
      RESULTS: From 954 identified articles, nine controlled studies, mainly comprising
      a medication review, were included (2542 patients). These interventions were
      associated with significant reductions in the mean number of omitted drugs per
      patient (estimate from six studies with 1469 patients: - 0.44; 95% confidence
      interval -0.61, -0.26) and the proportion of patients with >=1 omitted drugs
      (odds ratio from eight studies with 1833 patients: 0.29; 95% confidence interval
      0.13, 0.63). The only significant influential factor for improving success was
      the utilization of explicit screening instruments when conducting a medication
      review (P = 0.033). CONCLUSION: Pharmaceutical care interventions, including
      medication reviews, can significantly reduce medication underuse in older people.
      The use of explicit screening instruments alone or in combination with implicit
      reasoning is strongly recommendable for clinical practice.

PMID- 25868942
TI  - Tinnitus in patients with temporo-mandibular joint disorder: Proposal for a new
      treatment protocol.
AB  - The present study was designed to verify the correlation between tinnitus and
      temporomandibular joint dysfunction.86 consecutive patients were enrolled in the
      study, all affected by subjective tinnitus without hearing impairment, from both
      genders, age between 18 and 60 years old. The final number of patients included
      in the study was 55. All patients received a temporo-mandibular joint
      examination. All the patients were asked to rate the severity of their symptoms
      before and after treatment using a VAS scale and the Tinnitus Handicap Inventory
      (THI) and they followed a standardized protocol for the investigation of
      tinnitus. All the subjects were monitored by the same researcher and they
      underwent the same splint treatment. The comparison between pre- and
      posttreatment phase scores showed in patients with predisposition of TMD and with
      TMD a statistically significant decrease of THI and VAS values. The
      characteristics of tinnitus and the degree of response to treatment confirmed the
      relationship between tinnitus and TMD. The authors believe that, when the most
      common causes of tinnitus, such as otologic disorders and neurological diseases
      are excluded, it is correct to evaluate the functionality of the temporo
      mandibular joint and eventually treat its pathology to obtain tinnitus
      improvement or even resolution. 

PMID- 25868943
TI  - Proteogenomic Analysis of Trichophyton rubrum Aided by RNA Sequencing.
AB  - Infections caused by dermatophytes, Trichophyton rubrum in particular, are among
      the most common diseases in humans. In this study, we present a proteogenomic
      analysis of T. rubrum based on whole-genome proteomics and RNA-Seq studies. We
      confirmed 4291 expressed proteins in T. rubrum and validated their annotated gene
      structures based on 35 874 supporting peptides. In addition, we identified 323
      novel peptides (not present in the current annotated protein database of T.
      rubrum) that can be used to enhance current T. rubrum annotations. A total of 104
      predicted genes supported by novel peptides were identified, and 127 gene models
      suggested by the novel peptides that conflicted with existing annotations were
      manually assigned based on transcriptomic evidence. RNA-Seq confirmed the
      validity of 95% of the total peptides. Our study provides evidence that confirms
      and improves the genome annotation of T. rubrum and represents the first survey
      of T. rubrum genome annotations based on experimental evidence. Additionally, our
      integrated proteomics and multisourced transcriptomics approach provides stronger
      evidence for annotation refinement than proteomic data alone, which helps to
      address the dilemma of one-hit wonders (uncertainties supported by only one
      peptide). 

PMID- 25868945
TI  - Congenital syphilis presenting as Jarisch-Herxheimer reaction at birth.
AB  - We report a rare case of congenital syphilis (CS) presenting as Jarisch
      Herxheimer reaction (JHR) at birth. The mother (primigravida) presented in labor
      and had not received antenatal care. She was given prophylactic ampicillin 2 g
      i.v. on admission and delivered shortly thereafter. The male infant (2899 g) had
      normal vital signs, conjunctival congestion, splenohepatomegaly, and
      maculopapular rash with small blisters over the entire body. Serological tests on
      the infant and mother confirmed CS. The infant was given i.v. ampicillin for 14
      days (50 mg/kg per day until day 3, 100 mg/kg per day thereafter). One hour after
      the first injection, the infant developed fever (39 degrees C), tachycardia and
      tachypnea without worsening of rash. Vital signs improved gradually. The rash
      reduced markedly at postnatal day 1, and disappeared without pigmentation at day
      3. This was considered a JHR following ampicillin injection given to the mother
      before delivery and to the infant after birth.

PMID- 25868946
TI  - Stuve-Wiedemann syndrome in a neonate.
AB  - We describe a female neonate with Stuve-Wiedemann syndrome. The facial
      dysmorphism, joint contracture, distinctive skeletal changes, and myotonic
      discharges on electromyogram raised a suspicion of the rare autosomal recessive
      syndrome, which was later confirmed on molecular analysis of leukemia inhibitory
      factor receptor. She developed recurrent attacks of hyperpyrexia and died at age
      3 months.

PMID- 25868947
TI  - Rare causes of gastrointestinal hemorrhage in infancy.
AB  - Gastrointestinal hemorrhage in children is a critical condition that demands
      quick and effective management. The differential diagnosis of gastrointestinal
      hemorrhage is wide. Heterotopic pancreas is a rare congenital anomaly and usually
      discovered incidentally. It is generally asymptomatic, but symptoms may occur
      when complicated by inflammation, bleeding, obstruction or malign transformation.
      Heterotopic pancreas may present throughout the gastrointestinal tract, but it is
      most commonly found in the stomach, duodenum and proximal jejunum. Juvenile
      polyps are common during childhood and present most often with painless rectal
      hemorrhage. They remain the most common colonic polyps in children. Colonoscopic
      polypectomy is the most effective procedure in the treatment of juvenile polyps.
      In this study, we describe rare causes of gastrointestinal system hemorrhage in
      infancy and discuss some diagnostic and therapeutic approaches. 

PMID- 25868948
TI  - Radiological improvement by tocilizumab in polyarticular juvenile idiopathic
      arthritis.
AB  - Recent advances in biologic therapy have enabled reduction of the progression of
      destructive arthritis in rheumatoid arthritis. Once destroyed, however, the
      affected bones and cartilage are not fully repaired. We describe the case of an 8
      year-old girl with anti-citrullinated peptide antibody (ACPA)-positive
      polyarticular juvenile idiopathic arthritis (p-JIA). Destructive arthritis
      progressed during combination therapy with infliximab, methotrexate, mizoribine
      and prednisolone. Clinical remission was achieved, however, after switching the
      biologic agent to tocilizumab, a humanized monoclonal antibody to interleukin-6
      receptor. Both bone erosion and bone marrow edema on magnetic resonance imaging
      were repaired in association with restoration of joint spaces. Furthermore, there
      was no relapse of arthritis on weekly methotrexate alone for 2 years after
      discontinuation of the tocilizumab. Tocilizumab led to radiological repair of
      both bone and cartilage destruction and long-term biologics-free remission in a
      patient with ACPA-positive p-JIA, and should be considered for tumor necrosis
      factor inhibitor-resistant cases. 

PMID- 25868949
TI  - Medullary nephrocalcinosis in Schimke immuno-osseous dysplasia.
AB  - Schimke immuno-osseous dysplasia (SIOD) is a rare hereditary disease
      characterized by skeletal dysplasia, immune deficiency and progressive renal
      disease. Kidney involvement mainly determines the prognosis. The most common
      renal pathology is focal segmental glomerulosclerosis (FSGS). Medullary
      nephrocalcinosis refers to the diffuse deposition of calcium salts in renal
      medulla and has not previously been identified in SIOD. Here we report the first
      case of a pediatric patient having typical features of SIOD with medullary
      nephrocalcinosis. 

PMID- 25868950
TI  - Autoimmune-type atypical hemolytic uremic syndrome treated with eculizumab as
      first-line therapy.
AB  - We report a case of atypical hemolytic uremic syndrome (aHUS) in a 4-year-old
      boy. Although the patient had the typical triad of aHUS (microangiopathic
      hemolytic anemia, thrombocytopenia, and acute kidney injury), urgent dialysis was
      not indicated because he had neither oliguria nor severe electrolyte abnormality.
      He was given eculizumab as first-line therapy, which led to significant clinical
      improvement, thus avoiding any risk of complications associated with plasma
      exchange and central venous catheterization. Retrograde functional analysis of
      the patient's plasma using sheep erythrocytes indicated an increase in hemolysis,
      suggesting impairment of host cell protection by complement factor H. The use of
      eculizumab as first-line therapy in place of plasma exchange might be reasonable
      for pediatric patients with aHUS. 

PMID- 25868951
TI  - Stenosing ureteritis in Henoch-Schonlein purpura: report of two cases.
AB  - Stenosing ureteritis (SU), a rare complication of Henoch-Schonlein purpura (HSP),
      typically presents with severe symptoms. We report the cases of two HSP patients
      presenting with gross hematuria, blood clotting, and colicky flank pain, followed
      by purpura on the lower extremities. Early-stage ultrasonography indicated
      hydronephrosis, thickened renal pelvic mucous membrane, and ureteral dilatation
      (UD), suggesting HSP complicated with SU. After early SU treatment with
      prednisolone, kidney function, thickened renal pelvic mucous membrane, and UD
      progressively normalized and the pain gradually disappeared. Regular
      ultrasonography of HSP patients from the onset of gross hematuria can be useful
      to detect early SU and facilitate conservative therapy with prednisolone.
      Diagnosis of SU can be easily missed by assuming HSP nephritis, particularly
      owing to the non-specific symptoms. Common characteristics as well as treatment
      methods and prognosis of SU are given in the literature review. 

PMID- 25868952
TI  - Novel DCX mutation-caused lissencephaly in a boy and very mild heterotopia in his
      mother.
AB  - We describe a novel mutation in DCX in a family in which a proband boy had
      classical lissencephaly and his mother had extremely mild subcortical band
      heterotopia. No factors that would make the mother's symptoms milder, such as
      somatic mosaicism or skewed X chromosome inactivation, were observed. From this
      family, we conclude that a DCX mutation causes a pleiotropic phenotype in the
      female even if X chromosome inactivation pattern is not skewed, and the novel
      missense mutation in DCX produced relatively mild dysfunction of the doublecortin
      protein. 

PMID- 25868953
TI  - Japanese familial case of myoclonus-dystonia syndrome with a splicing mutation in
      SGCE.
AB  - Myoclonus-dystonia syndrome (MDS) is a rare autosomal-dominant movement disorder
      characterized by brief, frequently alcohol-responsive myoclonic jerks that begin
      in childhood or early adolescence, caused by mutations in the epsilon-sarcoglycan
      gene (SGCE). The patient was a 6-year-old boy. At 2 years 8 months, he had
      abnormal movement when he ran due to dystonia of his left leg. At 3 years 5
      months, he exhibited dystonia and myoclonic movement of his arms when eating.
      Myoclonus was likely to develop when he felt anxiety or exhaustion. Genomic DNA
      showed a heterozygous mutation in SGCE (c.109 + 1 G > T). His father and uncle
      with the same mutation also experienced milder dystonia or myoclonic movements.
      SGCE mutation can cause a broad range of clinical symptoms between and within
      families. We should consider MDS as a differential diagnosis for patients with
      paroxysmal walking abnormalities and/or myoclonic movements. 

PMID- 25868954
TI  - Angioplasty for recurrent renal artery stenosis in flare-up of Hashimoto's
      thyroiditis.
AB  - Takayasu arteritis is the most common disease seen in children presenting with
      renovascular hypertension (RVH) in Asia, and can manifest anatomically as renal
      artery stenosis (RAS). We report the case of a 16-year-old girl presenting with
      RVH due to recurrent and novel RAS in Hashimoto's thyroiditis (HT) flare-up.
      After treatment with thyroxin and percutaneous transluminal renal angioplasty
      (PTRA), she was free of hypothyroidism and systemic hypertension. RVH due to
      recurrent and novel RAS in HT flare-up has not previously been reported in the
      English-language literature. PTRA is the procedure of choice, providing there is
      no renal artery dissection or aneurysm. 

PMID- 25868955
TI  - Effective eculizumab therapy followed by BMT in a boy with paroxysmal nocturnal
      hemoglobinuria.
AB  - A 9-year-old boy with paroxysmal nocturnal hemoglobinuria/aplastic anemia
      syndrome (PNH/AA) developed hemolytic crisis after receiving immunosuppressive
      therapy. Eculizumab dramatically relieved the signs and symptoms and then he
      safely underwent unrelated bone marrow transplantation, suggesting the
      feasibility and effectiveness of eculizumab before stem cell transplantation in
      children with PNH/AA in hemolytic crisis. 

PMID- 25868956
TI  - Rituximab-combination chemotherapy achieves a 10th cycle of remission for
      Burkitt's lymphoma.
AB  - A 14-year-old girl with multiple intra-abdominal tumors was diagnosed with stage
      III Burkitt's lymphoma. She achieved complete remission after multi-drug
      chemotherapy, but she relapsed after six courses. Autologous peripheral blood
      stem cells (PBSC) or allogeneic PBSC harvested from an HLA-identical sibling were
      insufficient, and her family did not agree to bone marrow collection from the
      sibling. Although the patient relapsed nine times (the relapses involved intra
      abdominal organs or bone) during the following 4 years 7 months, treatment with
      rituximab monotherapy or in combination with ifosphamide, carboplastin, and
      etoposide, or local irradiation (33.8-40.0 Gy) to treat the bone metastases,
      proved effective, resulting in complete or partial remission. At the time of
      writing, the patient was in a 10th cycle of remission lasting 1 year 6 months and
      had not required transplantation. Thus, a chemotherapy regimen including
      rituximab might be effective for Burkitt's lymphoma in patients experiencing
      multiple relapse.

PMID- 25868957
TI  - Diffuse neonatal hemangiomatosis in a very low-birthweight infant treated with
      erythropoietin.
AB  - Diffuse neonatal hemangiomatosis (DNH) is a rare condition characterized by the
      concomitant development of multiple cutaneous infantile hemangiomas (IH) and
      visceral hemangiomas. Recently, an association between erythropoietin treatment
      and an increased incidence of infantile hemangioma was noted. A Japanese male
      infant was born via cesarean section at 27 weeks of gestation. Following the
      commencement of erythropoietin treatment for anemia of prematurity, he developed
      multiple cutaneous hemangiomas, high cardiac output heart failure and
      hepatomegaly. Abdominal imaging indicated comorbidity of diffuse infantile
      hepatic hemannigomas, resulting in the final diagnosis of DNH. The
      discontinuation of erythropoietin treatment and long-term therapy with
      propranolol improved the hepatic lesions and cutaneous hemangiomas. The
      possibility of multiple organ involvement and the exacerbating effects of
      erythropoietin treatment should be considered in cases in which multiple
      cutaneous hemangiomas develop in preterm infants receiving erythropoietin
      treatment.

PMID- 25868958
TI  - Hemophagocytic lymphohistiocytosis secondary to Varicella zoster infection in a
      child with Henoch-Schonlein purpura.
AB  - Hemophagocytic lymphohistiocytosis (HLH) is a fatal, hyper-inflammatory syndrome
      that is characterized by untimely activation of macrophages, and manifests as
      cytopenia, organ dysfunction, and coagulopathy. Secondary HLH can be associated
      with infection, drugs, malignancy, and transplantation, and is mostly triggered
      by infection. Herein, we report the case of a patient with Henoch-Schonlein
      purpura (HSP) who developed severe HLH secondary to Varicella zoster infection. 

PMID- 25868959
TI  - Successful diuretics treatment of protein-losing enteropathy in Noonan syndrome.
AB  - There are few reports on successful high-dose spironolactone treatment of
      refractory protein-losing enteropathy (PLE) caused by Fontan procedure. We report
      successful diuretics treatment with spironolactone and furosemide at standard
      dose, of refractory PLE in a patient with Noonan syndrome and repaired congenital
      heart disease. This is the first successful application of diuretics treatment in
      a patient with refractory PLE without Fontan procedure. This case illustrates
      that diuretics treatment can be the first-line treatment of PLE regardless of the
      causative physiology, and can be effective in refractory PLE with Noonan
      syndrome. 

PMID- 25868960
TI  - Severe visual loss caused by unrecognized malignant hypertension in a 15-year-old
      girl.
AB  - A 15-year-old girl presented with acute bilateral loss of central visual acuity
      due to hypertensive retinopathy level IV. She was found to have unrecognized
      malignant arterial hypertension associated with end-stage renal failure. At the
      time of diagnosis she also had severe left ventricular hypertrophy (LVH).
      Hypertension was successfully treated with combined anti-hypertensive therapy,
      but renal function did not recover. The patient underwent successful kidney
      transplant 4 months later and over a period of 20 months hypertensive retinopathy
      and LVH gradually resolved. This report emphasizes the importance of routine
      measurement of blood pressure and describes the possible consequences of
      unrecognized arterial hypertension in children. Early diagnosis and appropriate
      treatment are necessary to avoid development and progression of target organ
      damage and promote better long-term cardiovascular prognosis. 

PMID- 25868961
TI  - Diffuse alveolar hemorrhage secondary to ANCA-associated vasculitis in a patient
      with Down syndrome.
AB  - Diffuse alveolar hemorrhage (DAH) is a rare disease characterized by dyspnea,
      cough, hemoptysis, and new alveolar infiltrates. Among the various underlying
      disorders, vasculitis is believed to play a significant role in the pathogenesis
      of DAH. Here we report the first case of a patient with Down syndrome who
      developed DAH secondary to anti-neutrophil cytoplasmic antibody-associated
      vasculitis. This case highlights the significance of vasculitis as well as
      pulmonary hypoplasia and vulnerability associated with Down syndrome in the
      development of DAH. 

PMID- 25868962
TI  - Development of acute pancreatitis after Nissen fundoplication.
AB  - Acute pancreatitis subsequent to Nissen fundoplication for gastroesophageal
      reflux disease (GERD) is an extremely rare adverse event. We describe a pediatric
      case of acute pancreatitis resulting from superior mesenteric artery syndrome
      (SMAS) and gas bloat after fundoplication. Gas bloat is one of the known
      postoperative complications after Nissen fundoplication. Poor nutrition status,
      which is often associated with severe pediatric GERD, is a risk factor for SMAS.
      In this case, development of gas bloat and SMAS led to the formation of a closed
      loop and increased intraluminal pressure of the duodenum and pancreatic duct.
      Many pediatric patients who need anti-reflux surgery face the risk of developing
      this entity. Preventive measures, such as treatment with prokinetics and frequent
      small-volume meals, should be considered until improvement of nutritional status
      after fundoplication. 

PMID- 25868963
TI  - Severe intrinsic acute kidney injury associated with therapeutic doses of
      acetaminophen.
AB  - Acetaminophen is a commonly used medication to manage fever and pain in children
      and the drug is generally considered to be safe when used at appropriate
      therapeutic dosages. Recently, we encountered the case of a 3-year-old Japanese
      girl who suffered from severe intrinsic acute kidney injury (AKI) after
      therapeutic doses of acetaminophen for a fever due to viral infection. Renal
      biopsy indicated severe acute tubular necrosis with a significant striped
      interstitial fibrosis and mild interstitial inflammation. Unfortunately, she
      developed chronic kidney disease thereafter. This is the youngest case of biopsy
      proven severe intrinsic AKI associated with therapeutic doses of acetaminophen.
      Acetaminophen, even if administered at therapeutic dosages, may be dangerous in
      selected children, especially with possible pre-existing volume depletion. 

PMID- 25868964
TI  - Effect of African-American Race on Tumor Recurrence After Radical Cystectomy for
      Urothelial Carcinoma of the Bladder.
AB  - BACKGROUND: African-American race appears to be associated with higher stages of
      urothelial carcinoma of the bladder (UCB) at presentation and poorer survival.
      However, the independent effect of African-American race on objective tumor
      recurrence after radical cystectomy (RC) after controlling for clinical and
      pathologic variables is unknown. PATIENTS AND METHODS: The data from consecutive
      patients with UCB who underwent RC with curative intent at a single institution
      (University of Alabama, Birmingham) from 2001 to 2012 with or without
      perioperative chemotherapy or chemoradiation were reviewed. The patient
      demographics, risk factors, clinical course, pathologic characteristics, and long
      term outcomes were collected. Descriptive statistics were performed. Cox
      regression analysis was performed for key clinical, demographic, and pathologic
      variables, including race, stratified as African American versus white. RESULTS:
      A total of 215 patients, 163 men (76%) and 52 women (24%), with a mean age at RC
      of 65.6 years, were identified and reviewed. A total of 186 patients (87%) were
      white and 28 (13%) were African American. The median follow-up period after RC
      was 17.6 months. On conventional multivariate analysis, African-American race
      nearly attained statistical significance (hazard ratio [HR], 2.48; 95% confidence
      interval [CI], 0.98-6.29; P = .055). In a stepwise regression model, race was
      significantly associated with tumor recurrence (HR, 3.11; 95% CI, 1.2-7.4; P <
      .011). CONCLUSION: African-American race appears to be independently associated
      with a greater risk of tumor recurrence after RC for UCB. The effect of host
      genetics on tumor biology needs to be characterized at the genomic level to
      develop precision medicine.

PMID- 25868965
TI  - Impact of adjuvant chemotherapy with radiation for node-positive vulvar cancer: A
      National Cancer Data Base (NCDB) analysis.
AB  - BACKGROUND: For node-positive vulvar cancer, adjuvant radiotherapy has an
      established benefit, whereas the impact of chemotherapy is unknown. A National
      Cancer Data Base (NCDB) analysis was conducted to determine patterns of care and
      evaluate the survival impact of adjuvant chemotherapy. METHODS: The NCDB was
      queried for vulvar cancer patients diagnosed from 1998-2011 who underwent
      extirpative surgery with confirmed inguinal nodal involvement treated with
      adjuvant radiotherapy. Patients with inadequate follow-up or non-squamous
      histologies were excluded. Chi-square test, logistic regression analysis, log
      rank test and multivariable Cox proportional regression modeling with adjustment
      using propensity score with inverse probability of treatment weights (IPTW) were
      conducted to establish factors associated with utilization and survival. RESULTS:
      A total of 1797 patients were identified: 26.3% received adjuvant chemotherapy
      and 76.6% had 1-3 involved lymph nodes. Adoption of adjuvant chemotherapy
      significantly increased over time, from 10.8% in 1998 to 41.0% in 2006 (p<0.001).
      Lower utilization was seen in older patients, Northeast or Southern facilities,
      and patients with more extensive nodal dissection, whereas greater number of
      involved nodes, stage IVA disease and positive surgical margins led to a higher
      probability of receiving chemotherapy. Unadjusted median survival without and
      with adjuvant chemotherapy was 29.7months and 44.0months (p=0.001). On IPTW
      adjusted Cox proportional regression modeling, delivery of adjuvant chemotherapy
      resulted in a 38% reduction in the risk of death (HR 0.62, 95% CI 0.48-0.79,
      p<0.001). CONCLUSION: In a large population-based analysis, adjuvant chemotherapy
      resulted in a significant reduction in mortality risk for node-positive vulvar
      cancer patients who received adjuvant radiotherapy.

PMID- 25868966
TI  - The sooner the better: Genetic testing following ovarian cancer diagnosis.
AB  - OBJECTIVE: As treatment based genetic testing becomes a reality, it is important
      to assess the attitudes and preferences of women newly diagnosed with ovarian
      cancer regarding genetic testing. The objective of this study was to determine
      when women with a diagnosis of high grade serous ovarian cancer would prefer to
      undergo genetic testing and factors that influence this preference. METHODS:
      Women over 18years of age with a known diagnosis of high grade serous ovarian
      cancer diagnosed between October 2010-2013 were identified via the Princess
      Margaret Cancer Center Registry. Participants completed a questionnaire, which
      obtained preferences and attitudes towards genetic testing, cancer history, and
      demographic information. RESULTS: 120 of the 355 women identified (33.8%)
      completed the questionnaires. The median age at time of ovarian cancer diagnosis
      was 57years (range 35-84). The majority of participants in this study were
      offered (94.6%) and pursued (84.8%) genetic testing. In this cohort, testing was
      most frequently offered at diagnosis (41.8%) or during treatment (19.1%). In this
      study, women with high grade serous ovarian cancer felt that genetic testing
      should be offered before or at the time of diagnosis (67.8%). Having a family
      history of breast or ovarian cancer was significantly (p=0.012) associated with
      preferring genetic testing at an earlier time point in the disease course.
      CONCLUSIONS: Our results demonstrate that women with high grade serous ovarian
      cancer acknowledge the personal and clinical utility of genetic testing and
      support test implementation at the time of cancer diagnosis.

PMID- 25868967
TI  - The clinical value of surgeons' efforts of preventing intraoperative tumor
      rupture in stage I clear cell carcinoma of the ovary: A Korean multicenter study.
AB  - OBJECTIVE: To demonstrate the survival impact of intraoperative tumor rupture in
      women with stage I clear cell carcinoma (CCC) of the ovary. METHODS: A total of
      193 patients with stage I CCC of the ovary who had undergone a complete staging
      operation followed by >=three cycles of adjuvant platinum-based chemotherapy,
      were retrospectively reviewed. Survival analysis was performed and compared
      between three stage groups: IA/IB, IC1, and IC2/IC3. RESULTS: There were 70, 51,
      and 72 women with ovarian CCC in stages IA/IB, IC1, and IC2/IC3, respectively.
      Intraoperative tumor rupture occurred in 69 (35.8%) patients. Gross endometriosis
      (p=0.020) and significant peritumoral adhesion (p<0.001) were associated with
      intraoperative tumor rupture. However, neither laparoscopic approach nor large
      tumor size >10cm were associated with intraoperative tumor rupture. Patients with
      stage IC2/IC3 compared to those with stage IC1, had poorer progression-free
      survival (PFS) (5-year PFS, 68.5% versus 91.7%; p=0.010) and overall survival
      (OS) (5-year OS, 81.1% versus 95.4%; p=0.027). However, there was no significant
      difference between patients with stages IA/IB and IC1 CCC in PFS (5-year PFS
      88.8% versus 91.7%; p=0.291) and OS (5-year OS 94.6% versus 95.4%; p=0.444).
      Stage IC2/IC3 was the only independent poor prognostic factor for OS (hazard
      ratio, 3.50; 95% confidence interval, 1.31 to 9.36). CONCLUSION: Surgical
      spillage of tumor cells does not appear to have a negative impact on survival
      outcomes of women with stage I ovarian CCC who received >=three cycles of
      adjuvant platinum-based chemotherapy.

PMID- 25868968
TI  - Cell phone-induced chondrodermatitis nodularis antihelicis.

PMID- 25868969
TI  - Airway management in patients with burn contractures of the neck.
AB  - Airway management of patients with burn contracture of the neck (PBC neck) is a
      challenge to the anesthesiologist. Patient evaluation includes history, physical
      and airway examination. A safe approach in the airway management of a patient
      with moderate to severe PBC neck is to secure the airway with the patient awake.
      The anesthesiologist should have a pre-planned strategy for intubation of the
      difficult airway. The choices advocated for airway management of such patients
      include awake fiberoptic-guided intubation, use of intubating laryngeal mask
      airway, intubation without neuromuscular blocking agents, intubation with
      neuromuscular blocking agents after testing the ability to ventilate by mask, pre
      induction neck scar release under local anesthesia and ketamine or sedation
      followed by direct laryngoscopy and intubation and video-laryngoscope guided
      intubation, amongst others. Preparation of the patient includes an explanation of
      the proposed procedure, sedation, administration of antisialogogues and regional
      anesthesia of the airway. The various options for intubation of patients with PBC
      neck, intraoperative concerns and safe extubation are described. Back-up plans,
      airway rescue strategies and a review of literature on this subject are
      presented. 

PMID- 25868970
TI  - Differences between immediate and late onset of spinal cord ischemia after open
      and endovascular aortic interventions.
AB  - Spinal cord ischemia remains the most impressive and colliding complication
      following open surgical and endovascular aortic procedures. Paraparesis and
      paraplegia are devastating, having a major invalidating impact on the patient's
      life. Also for the surgeon and the entire team this dramatic adverse event causes
      a significant concussion. Surgeons faced this problem in practice in the 1950s
      when this surgery started being applied. Even A. Carrel in 1910 said, "The main
      danger of the aortic operation does not come from the heart or from the aorta
      itself, but from the central nervous system". As the number of these surgeries
      grew, some were followed by the spinal cord ischemia. Now, in 21st century,
      problem of spinal cord ischemia still exists. By understanding the reasons of its
      development we shall be able to find more useful methods for prevention as well
      as for the treatment. The aim of this article was to search what is behind this
      dreadful complication, explaining different mechanisms which take part in its
      development during endovascular and open surgical treatment. 

PMID- 25868971
TI  - Endovascular management of isolated iliac artery aneurysms.
AB  - Isolated iliac artery aneuryms are detected increasingly as a result of expanding
      use of diagnostic imaging, and screening programmes. This present review
      describes endovascular solutions for the management of isolated iliac artery
      aneurysms. This was a review of the published literature on endovascular
      treatment of iliac aneurysms. Most of the papers were case series, and there are
      no randomized studies. Aneurysms of the common iliac artery are most common,
      followed by internal, then external iliac aneurysms. Indications for intervention
      remain unclear, but are generally based on diameter. Endovascular solutions exist
      for at least half the aneurysms that required treatment, including as an
      emergency. Often a standard bifurcated solution, as for abdominal aortic aneurysm
      is indicated, however, there are a number of other novel solutions to deal with
      variable anatomy. Endovascular treatment of iliac aneurysms is less painful and
      reduces hospital stay. However, outcome data remain limited, and formal
      comparison with open surgery is awaited. 

PMID- 25868972
TI  - Critical limb ischemia and its treatments: a review.
AB  - Critical limb ischemia (CLI) encompasses the most extreme end of the peripheral
      artery disease (PAD) spectrum leading to significant morbidity and mortality. CLI
      is defined as greater than 2 weeks of extremity rest pain, ulcers or extremity
      gangrene, secondary to objectively proven peripheral artery disease.
      Corresponding to Fontaine Stages III/IV and Rutherford category IV through VI,
      CLI is a complex disease comprising of both macrovascular and microvascular
      systems with inconsistent historical data on optimal treatment. CLI is distinct
      from intermittent claudication with different goals of treatment, however in both
      groups risk factor modification is of the utmost importance involving tobacco
      cessation, and treatment of underlying conditions like diabetes mellitus,
      hyperlipidemia and hypertension. In CLI, medical therapy involves wound care and
      also consists of antiplatelet therapy, anti-inflammatory therapy including statin
      use or ACE inhibitors. Surgical therapies include distal bypass surgery,
      thromboendartectomy and amputation. Endovascular techniques include percutaneous
      transluminal angioplasty, bare metal stents, atherectomy, drug-coated balloon and
      drug-eluting stents. CLI is considered the end-stage of PAD, requiring a
      thoughtful and multidisciplinary approach, risk-benefit analysis and treatment of
      comorbid conditions. Conservative and surgical treatments, along with
      endovascular techniques, have allowed excellent opportunities for treating
      complicated patients for wound healing and limb salvage. 

PMID- 25868973
TI  - Contemporary management of blunt aortic trauma.
AB  - Blunt thoracic aortic injury (BTAI) remains a common cause of death following
      blunt mechanisms of trauma. Among patients who survive to reach hospital care,
      significant advances in diagnosis and treatment afford previously unattainable
      survival. The Society for Vascular Surgery (SVS) guidelines provide current best
      evidence suggestions for treatment of BTAI. However, several key areas of
      controversy regarding optimal BTAI care remain. These include the refinement of
      selection criteria, timing for treatment and the need for long-term follow-up
      data. In addition, the advent of the Aortic Trauma Foundation (ATF) represents an
      important development in collaborative research in this field. 

PMID- 25868974
TI  - Open treatment of extent IV thoracoabdominal aortic aneurysms.
AB  - AIM: Extent IV thoracoabdominal aortic aneurysm (TAAA) open repair is considered
      relatively safer to repair than other extents of TAAA in terms of both
      perioperative mortality and spinal cord ischemia. Our purpose is to report our
      experience and to perform a literature review regarding extent IV TAAA open
      repair in order to provide an updated benchmark for comparison with any other
      alternative strategy in this aortic segment. METHODS: From 1993 to 2015 we
      performed 736 open repairs for TAAA (177 extent I, 196 extent II, 141 extent III,
      222 extent IV). In extent IV group there were 164 men (73.9%) and the mean age
      was 67.4+/-9.3 years (range 32-84). The aneurysm etiology was degenerative in 198
      patients (95.6%). Twelve patients (5.4%) underwent emergent operation. Totally
      abdominal approach was used in 22.0% of the cases. Until 2006 left heart bypass
      (LHBP) and cerebrospinal fluid drainage (CSFD) were almost never performed during
      extent IV repair. Since 2006 we changed our approach with a more aggressive use
      of LHBP (22.9%) and CSFD (43.4%) in 83 consecutive extent IV. Renal arteries
      perfusion was performed with 4  degrees C Ringer's solution until 2009 and with 4
      degrees C Custodiol solution since September 2009 to date. Literature search was
      performed on several databases (PubMed, BioMedCentral, Embase, and the Cochrane
      Central Register of clinical trials). Research was updated on March 1th 2015.
      RESULTS: Perioperative mortality in our overall group of TAAA and in the extents
      IV was 10.7% and 4.9%, respectively (P=0.01); spinal cord ischemia rate 11.4% and
      2.7%, respectively (P=0.0001). In the extents IV treated between 2006 and 2015 we
      observed a further trend of outcomes improvement with a rate of perioperative
      mortality and spinal cord ischemia of 1.2%, and 2.4%, respectively. Database
      searches yielded a total of 767 articles. Excluding non-pertinent titles or
      abstracts, we retrieved in complete form and assessed 27 studies according to the
      selection criteria. Nine studies were further excluded because of our
      prespecified exclusion criteria. The final 18 manuscripts included a total of
      2098 patients. In this group median mortality rate was 4.8% (interquartile range
      3-6) and the mean incidence of spinal cord ischemia was 1.56+/-1.54%. CONCLUSION:
      Perioperative outcomes after extent IV TAAA open repair were significantly better
      compared to our overall TAAA series. A more aggressive use of CSFD, LHBP and
      renal perfusion with Custodiol solution allowed a further trend of outcomes
      improvement in our series of extent IV TAAA open repair. Literature analysis
      confirmed during extent IV open repair very satisfactory perioperative outcomes
      with rates of mortality and spinal cord ischemia dropped to under 5% and 2%,
      respectively.

PMID- 25868975
TI  - HIPK2 deficiency causes chromosomal instability by cytokinesis failure and
      increases tumorigenicity.
AB  - HIPK2, a cell fate decision kinase inactivated in several human cancers, is
      thought to exert its oncosuppressing activity through its p53-dependent and 
      independent apoptotic function. However, a HIPK2 role in cell proliferation has
      also been described. In particular, HIPK2 is required to complete cytokinesis and
      impaired HIPK2 expression results in cytokinesis failure and tetraploidization.
      Since tetraploidy may yield to aneuploidy and chromosomal instability (CIN), we
      asked whether unscheduled tetraploidy caused by loss of HIPK2 might contribute to
      tumorigenicity. Here, we show that, compared to Hipk2+/+ mouse embryo fibroblasts
      (MEFs), hipk2-null MEFs accumulate subtetraploid karyotypes and develop CIN.
      Accumulation of these defects inhibits proliferation and spontaneous
      immortalization of primary MEFs whereas increases tumorigenicity when MEFs are
      transformed by E1A and Harvey-Ras oncogenes. Upon mouse injection, E1A/Ras
      transformed hipk2-null MEFs generate tumors with genetic alterations resembling
      those of human cancers derived by initial tetraploidization events, such as
      pancreatic adenocarcinoma. Thus, we evaluated HIPK2 expression in different
      stages of pancreatic transformation. Importantly, we found a significant
      correlation among reduced HIPK2 expression, high grade of malignancy, and high
      nuclear size, a marker of increased ploidy. Overall, these results indicate that
      HIPK2 acts as a caretaker gene, whose inactivation increases tumorigenicity and
      causes CIN by cytokinesis failure. 

PMID- 25868976
TI  - Tyrosine-protein phosphatase non-receptor type 12 expression is a good prognostic
      factor in resectable non-small cell lung cancer.
AB  - Tyrosine-protein phosphatase non-receptor type 12 (PTPN12) has been considered to
      be a tumor suppressor in human cancer, but its clinical and prognostic
      significance in non-small cell lung cancer (NSCLC) has not been well elucidated.A
      retrospective analysis of 215 patients with surgically resected NSCLCs from Sun
      Yat-Sen University Cancer Center between April 2002 and March 2005 was performed
      using immunohistochemistry and Western Blot to analyze PTPN12 expression. The
      association between PTPN12 expression and patient survival was
      investigated.Western Blots showed that the expression level of PTPN12 were higher
      in normal paracancerous lung tissues than in NSCLC tissues. High PTPN12
      expression was less common in the presence than in the absence of visceral
      pleural invasion (p=0.038). Patients with PTPN12-high tumors had a longer disease
      free survival (DFS) (P<0.001) and overall survival (OS) (p<0.001), especially for
      those with non-squamous cell carcinoma (non-SCC) (DFS, p<0.001; OS, p<0.001).
      Multivariate analysis confirmed that PTPN12 positivity was associated with
      increased survival duration (DFS, p<0.001; OS, p<0.001), independent of
      prognostic indicator.High PTPN12 expressive levels are associated with favorable
      survival duration in patients with NSCLC, especially those with non-SCC. Our
      study suggests that PTPN12 expression is a valuable prognostic biomarker for
      NSCLC patients. 

PMID- 25868977
TI  - Triple negative breast cancers comprise a highly tumorigenic cell subpopulation
      detectable by its high responsiveness to a Sox2 regulatory region 2 (SRR2)
      reporter.
AB  - We have recently described a novel phenotypic dichotomy within estrogen receptor
      positive breast cancer cells; the cell subset responsive to a Sox2 regulatory
      region (SRR2) reporter (RR cells) are significantly more tumorigenic than the
      reporter unresponsive (RU) cells. Here, we report that a similar phenomenon also
      exists in triple negative breast cancer (TNBC), with RR cells more tumorigenic
      than RU cells. First, examination of all 3 TNBC cell lines stably infected with
      the SRR2 reporter revealed the presence of a cell subset exhibiting reporter
      activity. Second, RU and RR cells purified by flow cytometry showed that RR cells
      expressed higher levels of CD44, generated more spheres in a limiting dilution
      mammosphere formation assay, and formed larger and more complex structures in
      Matrigel. Third, within the CD44(High)/CD24- tumor-initiating cell population
      derived from MDA-MB-231, RR cells were significantly more tumorigenic than RU
      cells in an in vivo SCID/Beige xenograft mouse model. Examination of 4 TNBC
      tumors from patients also revealed the presence of a RR cell subset, ranging from
      1.1-3.8%. To conclude, we described a novel phenotypic heterogeneity within TNBC,
      and the SRR2 reporter responsiveness is a useful marker for identifying a highly
      tumorigenic cell subset within the CD44(High)/CD24-tumor-initiating cell
      population.

PMID- 25868980
TI  - Selective B-B bond activation in an unsymmetrical diborane(4) by [(Me3P)4Rh-X] (X
      = Me, OtBu): a switch of mechanism?
AB  - The unsymmetrical diborane(4) pinB-B((RN)2(C6H4)) (R = Me, Bn) reacts with
      [(Me3P)4Rh-X] (X = Me, OtBu) giving predominantly either [(Me3P)4Rh-Bpin] or
      [(Me3P)3Rh-B((RN)2(C6H4))] depending on X. At low temperatures in the presence of
      excess PMe3 the unprecedented equatorial boryl complex [(Me3P)4Rh
      B((MeN)2(C6H4))] is formed. 

PMID- 25868978
TI  - Resistin and interleukin-6 exhibit racially-disparate expression in breast cancer
      patients, display molecular association and promote growth and aggressiveness of
      tumor cells through STAT3 activation.
AB  - African-American (AA) women with breast cancer (BC) are diagnosed with more
      aggressive disease, have higher risk of recurrence and poorer prognosis as
      compared to Caucasian American (CA) women. Therefore, it is imperative to define
      the factors associated with such disparities to reduce the unequal burden of
      cancer. Emerging data suggest that inherent differences exist in the tumor
      microenvironment of AA and CA BC patients, however, its molecular bases and
      functional impact have remained poorly understood. Here, we conducted cytokine
      profiling in serum samples from AA and CA BC patients and identified resistin and
      IL-6 to be the most differentially-expressed cytokines with relative greater
      expression in AA patients. Resistin and IL-6 exhibited positive correlation in
      serum levels and treatment of BC cells with resistin led to enhanced production
      of IL-6. Moreover, resistin also enhanced the expression and phosphorylation of
      STAT3, and treatment of BC cells with IL-6-neutralizing antibody prior to
      resistin stimulation abolished STAT3 phosphorylation. In addition, resistin
      promoted growth and aggressiveness of BC cells, and these effects were mediated
      through STAT3 activation. Together, these findings suggest a crucial role of
      resistin, IL-6 and STAT3 in BC racial disparity. 

PMID- 25868979
TI  - A STAT3-NFkB/DDIT3/CEBPbeta axis modulates ALDH1A3 expression in chemoresistant
      cell subpopulations.
AB  - Here we studied the relevance and modulation of aldehyde dehydrogenase (ALDH)
      expression in malignant pleural mesothelioma (MPM) chemoresistant cell
      subpopulations (ALDH(bright) cells), which survive pemetrexed + cisplatin
      treatment in vitro and in vivo. Expression of the ALDH1A3 isoform was invariably
      enriched in purified ALDH(bright) cells from multiple MPM cell lines and
      accounted for the enzymatic activity of those cells. RNAi mediated downregulation
      of ALDH1A3 reduced the survival of the ALDH(bright) cells at steady state and,
      much more, after pemetrexed + cisplatin treatment. We demonstrated, for the first
      time, that a pSTAT3(tyr705)-NFkB(p65) complex is required for the repression of
      DDIT3 mRNA and this ensures high levels of CEBPbeta-dependent ALDH1A3 promoter
      activity. Inhibition of STAT3-NFkB activity allowed high levels of DDIT3
      expression with increased formation of a DDIT3-CEBPbeta complex. This reduced the
      occupancy of the ALDH1A3 promoter by CEBPbeta, thus largely reducing the ALDH1A3
      expression. Consequently, survival of ALDH(bright) cells in pemetrexed +
      cisplatin-treated cultures was impaired, following increased apoptosis. We show
      that such a mechanism is relevant in vivo and underlies the action of butein, a
      dual STAT3-NFkB inhibitor capable of abating the chemoresistance of mesothelioma
      cells in vivo. The possible broad translational relevance of the described
      mechanism is discussed.

PMID- 25868981
TI  - Suppression of Th2 chemokines by crocin via blocking of ERK-MAPK/NF-kappaB/STAT1
      signalling pathways in TNF-alpha/IFN-gamma-stimulated human epidermal
      keratinocytes.

PMID- 25868983
TI  - The art in science of MicroTAS: the 2014 issue.

PMID- 25868982
TI  - Phosphorylation of Leghemoglobin at S45 is Most Effective to Disrupt the
      Molecular Environment of Its Oxygen Binding Pocket.
AB  - In leguminous plants, nitrogenase that catalyzes anaerobic symbiotic nitrogen
      fixation is protected by the sequestration of O2 by Leghemoglobin (LegH). The
      modulation of the oxygen binding capacity of Hemoglobin (Hb) by different post
      translational modifications is well studied; whereas similar studies on LegH's O2
      binding are not yet benchmarked. Our results show that in vitro serine
      phosphorylation of recombinant LegH from Lotus japonicus, a model legume, by a
      homologous kinase caused a reduction in its oxygen consumption as determined by
      Clark type electrode. Although mass spectrometry revealed a few phosphorylated
      serine residues in the LegH, molecular modeling study showed that particularly
      S45 is the most critical one, along with S55, however the latter with lesser
      impact on its molecular environment responsible for oxygen consumption. Separate
      S45D and S55D mutants of recombinant LegH also corroborated the results obtained
      from molecular modeling study. Thus, this work lays groundwork for further
      investigation of structural and functional role of serine phosphorylation as one
      of the mechanisms by which oxygen consumption by LegH may possibly be regulated
      during nodulation. 

PMID- 25868984
TI  - Motor cortex layer 4: less is more.
AB  - The stratified motor cortex is variously thought to either lack or contain layer
      4. Yamawaki et al. described a functional layer 4 in mouse motor cortex with
      properties and connections similar to layer 4 in sensory areas. Their results
      bolster a theoretical framework suggesting all primary cortical areas are
      equivalent. 

PMID- 25868985
TI  - Environmental Changes in MoTe2 Excitonic Dynamics by Defects-Activated Molecular
      Interaction.
AB  - Monolayers of group VI transition metal dichalcogenides possess direct gaps in
      the visible spectrum with the exception of MoTe2, where its gap is suitably
      located in the infrared region but its stability is of particular interest, as
      tellurium compounds are acutely sensitive to oxygen exposure. Here, our
      environmental (time-dependent) measurements reveal two distinct effects on MoTe2
      monolayers: For weakly luminescent monolayers, photoluminescence signal and
      optical contrast disappear, as if they are decomposed, but yet remain intact as
      evidenced by AFM and Raman measurements. In contrast, strongly luminescent
      monolayers retain their optical contrast for a prolonged amount of time, while
      their PL peak blue-shifts and PL intensity saturates to slightly lower values.
      Our X-ray photoelectron spectroscopy measurements and DFT calculations suggest
      that the presence of defects and functionalization of these defect sites with O2
      molecules strongly dictate their material properties and aging response by
      changing the excitonic dynamics due to deep or shallow states that are created
      within the optical band gap. Presented results not only shed light on
      environmental effects on fundamental material properties and excitonic dynamics
      of MoTe2 monolayers but also highlight striking material transformation for
      metastable 2D systems such as WTe2, silicone, and phosphorene. 

PMID- 25868987
TI  - An historic meeting.

PMID- 25868986
TI  - The Still Enigmatic Syndrome of Transient Global Amnesia: Interactions Between
      Neurological and Psychopathological Factors.
AB  - Transient global amnesia (TGA) is a neurological syndrome that usually occurs in
      middle-aged or older people. It is characterized by the abrupt onset of profound
      anterograde amnesia, associated with more variable retrograde amnesia and
      repetitive questioning. The whole episode lasts no more than 24 h. Almost 60
      years after its first descriptions, the etiology of TGA remains unknown. Until
      now, TGA has been described exclusively as a memory disorder, but there is a
      growing body of evidence to show that emotional and psychological factors (as
      anxious and depressive symptoms) are present at different times of TGA. Their
      role therefore needs to be clarified. First, these factors seem to play a part in
      triggering TGA, at least for a subgroup of patients, suggesting the existence of
      an emotional TGA subtype. Second, recent research shows that almost all the TGA
      patients displayed modifications of their emotional state during the episode,
      possibly linked to sudden memory loss. The level of depressive and anxious
      symptoms could even reach a pathological threshold in patients with the so-called
      "emotional TGA subtype". Third, the persistence of these depressive and anxious
      symptoms after the end of the episode could account for lasting memory disorders
      in some patients. Finally, the analysis of these emotional syndrome and emotional
      factors and the recent data in neuroimaging could allow us to gain a better
      understanding of the pathophysiological mechanisms behind TGA. The aim of this
      review was thus to discuss whether the anxious and depressive symptoms are
      causative, resultant or coincidental of TGA.

PMID- 25868988
TI  - Emerging contaminants: a potential human health concern for sensitive
      populations.
AB  - Pharmaceuticals and other xenobiotic molecules are being increasingly detected in
      drinking water, food crops, and breast milk. This issue represents a novel
      toxicological concern, especially for sensitive populations like pregnant women
      and breastfeeding infants. This commentary calls for more interdisciplinary
      research efforts focused on elucidating the transfer of contaminants of emerging
      concern from mother to child, as well as the relevant toxicological impacts on
      the child. The need for more tangible efforts to reduce pharmaceutical loads in
      environmental systems is also highlighted.

PMID- 25868989
TI  - Adapting to Biology: Maintaining Container-Closure System Compatibility with the
      Therapeutic Biologic Revolution.
AB  - : Many pharmaceutical companies are transitioning their research and development
      drug product pipeline from traditional small-molecule injectables to the
      dimension of evolving therapeutic biologics. Important concerns associated with
      this changeover are becoming forefront, as challenges develop of varying
      complexity uncommon with the synthesis and production of traditional drugs.
      Therefore, alternative measures must be established that aim to preserve the
      efficacy and functionality of a biologic that might not be implemented for small
      molecules. Conserving protein stability is relative to perpetuating a net
      equilibrium of both intrinsic and extrinsic factors. Key to sustaining this
      balance is the ability of container-closure systems to maintain their
      compatibility with the ever-changing dynamics of therapeutic biologics. Failure
      to recognize and adjust the material properties of packaging components to
      support compatibility with therapeutic biologics can compromise patient safety,
      drug productivity, and biological stability. This review will examine the
      differences between small-molecule drugs and therapeutic biologics, lay a basic
      foundation for understanding the stability of therapeutic biologics, and
      demonstrate potential sources of container-closure systems' incompatibilities
      with therapeutic biologics at a mechanistic level. LAY ABSTRACT: Many
      pharmaceutical companies are transitioning their research and development drug
      product pipeline from traditional small-molecule injectables to recombinantly
      derived therapeutic biologics. Concerns associated with this transformation are
      becoming prominent, as therapeutic biologics are uncharacteristic to small
      molecule drugs. Maintaining the stability of a therapeutic biologic is a
      combination of balancing intrinsic factors and external elements within the
      biologic's microenvironment. An important aspect of this balance is relegated to
      the overall compatibility of primary, parenteral container-closure systems with
      therapeutic biologics. A packaging component within a container-closure system
      that is incompatible with the therapeutic biologic can potentially compromise
      patient safety, drug productivity, and product quality. Thus, each primary,
      parenteral packaging component within a container-closure system should be
      optimized to preserve the efficacy and therapeutic activity of a biologic. This
      review will examine the differences between small-molecule drugs and therapeutic
      biologics, lay a basic foundation for understanding the stability of therapeutic
      biologics, and demonstrate potential sources of container-closure system
      incompatibilities with therapeutic biologics at a mechanistic level.

PMID- 25868990
TI  - Studies of protein oxidation as a product quality attribute on a scale-down model
      for cell culture process development.
AB  - Of importance to the biological properties of proteins produced in cell culture
      systems are the complex post-translational modifications that are affected by
      variations in process conditions. Protein oxidation, oxidative modification to
      intracellular proteins that involves cleavage of the polypeptide chain, and
      modifications of the amino acid side chains can be affected by such process
      variations. Dissolved oxygen is a parameter of increasing interest since studies
      have shown that despite the necessity of oxygen for respiration, there may also
      be some detrimental effects of oxygen to the cell. Production and accumulation of
      reactive oxygen species can cause damage to proteins as a result of oxidation of
      the cell and cellular components. Variation, or changes to cell culture products,
      can affect function, clearance rate, immunogenicity, and specific activity, which
      translates into clinical implications. The effect of increasing dissolved oxygen
      on protein oxidation in immunoglobulin G3-producing mouse hybridoma cells was
      studied using 50 mL high-throughput mini-bioreactors that employ non-invasive
      optical sensor technology for monitoring and closed feedback control of pH and
      dissolved oxygen. Relative protein carbonyl concentration of proteins produced
      under varying levels of dissolved oxygen was measured by enzyme-linked
      immunosorbent assay and used as an indicator of oxidative damage. A trend of
      increasing protein carbonyl content in response to increasing dissolved oxygen
      levels under controlled conditions was observed. LAY ABSTRACT: Protein oxidation,
      oxidative modification to intracellular proteins that involves cleavage of the
      polypeptide chain, and modifications of the amino acid side chains can be
      affected by variations in dissolved oxygen levels in cell culture systems.
      Studies have shown that despite the necessity of oxygen for respiration, there
      may be detrimental effects of oxygen to the cell. Production and accumulation of
      reactive oxygen species can cause damage to proteins as a result of oxidation of
      the cell and cellular components, affecting function, clearance rate,
      immunogenicity, and specific activity, which translates into clinical
      implications. The effect of increasing dissolved oxygen on protein oxidation in
      immunoglobulin G3-producing mouse hybridoma cells was studied using 50 mL high
      throughput mini-bioreactors that employ non-invasive optical sensor technology
      for monitoring and closed feedback control of pH and dissolved oxygen. Protein
      carbonyl concentration of proteins produced under varying levels of dissolved
      oxygen was measured by enzyme-linked immunosorbent assay and used as an indicator
      of oxidative damage. A trend of increasing protein carbonyl content in response
      to increasing dissolved oxygen levels under controlled conditions was observed.

PMID- 25868991
TI  - Parallelism in practice: approaches to parallelism in bioassays.
AB  - Relative potency bioassays are used to estimate the potency of a test biological
      product relative to a standard or reference product. It is established practice
      to assess the parallelism of the dose-response curves of the products prior to
      calculating relative potency. This paper provides a review of parallelism testing
      for bioassays. In particular three common methods for parallelism testing are
      reviewed: two significance tests (the F-test, the chi(2)-test) and an equivalence
      test. Simulation is used to compare these methods. We compare the sensitivity and
      specificity and receiver operating characteristic curves, and find that both the
      chi(2)-test and the equivalence test outperform the F-test on average, unless the
      assay-to-assay variation is considerable. No single method is optimal in all
      situations. We describe how bioassay scientists and statisticians can work
      together to determine the best approach for each bioassay, taking into account
      its properties and the context in which it is applied. LAY ABSTRACT: Bioassays
      are experiments that use living organisms, tissues, or cells to measure the
      concentration of a pharmaceutical. Typically the response of the living matter to
      a test sample with an unknown concentration of a pharmaceutical is compared to
      the response to a standard reference sample with a known concentration. An
      important step in the analysis of bioassays is checking that the test sample is
      responding like a diluted copy of the reference sample; this is known as testing
      for parallelism. There are three statistical methods commonly used to test for
      parallelism: the F-test, the chi(2)-test, and the equivalence test. This paper
      compares the three methods using computer simulations. We conclude that different
      methods are best in different situations, and we provide guidelines to help
      bioassay scientists and statisticians decide which method to use.

PMID- 25868992
TI  - In-process microbial testing: statistical properties of a rapid alternative to
      compendial enumeration methods.
AB  - In-process tests are used between manufacturing steps to avoid the cost of
      further processing material that is apt to fail its final tests. Rapid
      microbiological methods that return simple negative or positive results are
      attractive in this context because they are faster than the compendial methods
      used at product release. However, using a single such test will not reliably
      detect barely unacceptable material (sensitivity) without generating an
      undesirable number of false rejections (poor specificity). We quantify how to
      achieve a balance between the risks of false acceptance and false rejection by
      performing multiple rapid microbiological methods and applying an acceptance
      rule. We show how the end user can use a simple (and novel) graph to choose a
      sample size, the number of samples, and an acceptance rule that yield a good
      balance between the two risks while taking cost (number of tests) into account.
      LAY ABSTRACT: In-process tests are used between manufacturing steps to avoid the
      cost of further processing material that is apt to fail its final tests. Rapid
      microbiological methods that return simple negative or positive results are
      attractive in this context because they are faster than the compendial methods
      used at product release. However, using a single such test will not reliably
      detect barely unacceptable material (sensitivity) without generating an
      undesirable number of false rejections (poor specificity). We quantify how to
      achieve a balance between the risks of false acceptance and false rejection by
      performing multiple rapid microbiological methods and applying an acceptance
      rule. We show how the end user can use a simple (and novel) graph to choose a
      sample size, the number of samples, and an acceptance rule that yield a good
      balance between the two risks while taking cost (number of tests) into account.

PMID- 25868993
TI  - Utilization of the tyndall effect for enhanced visual detection of particles in
      compatibility testing of intravenous fluids: validity and reliability.
AB  - PURPOSE: This study investigates the validity, reliability, and detection limit
      of a visual examination method utilizing the Tyndall effect to enhance visible
      detection of particles. The suitability of the method for compatibility testing
      of intravenous fluids in a hospital pharmacy context is discussed. METHODS: A
      panel of 20 inspectors examined 20 samples, with and without particles, using two
      light sources (halogen lightbulb in a focused desk lamp and a red pocket laser
      pointer). The samples contained particles of different origin (precipitate,
      polystyrene standards), varying size, and concentrations. Light obscuration and
      turbidimetric measurements were used to obtain numeric references. The samples
      were divided into rejection probability zones, and the validity (sensitivity,
      specificity, and likelihood ratios) and reliability (inter-rater agreement
      coefficients Fleiss' kappa and Gwet's AC1) were estimated. RESULTS: The
      sensitivity of the laser pointer for detecting microprecipitates was quite high;
      however, it also showed a high false rejection rate. The specificity was slightly
      higher for the focused desk lamp than the laser pointer. The likelihood ratios
      were not within the recommended limits of a useful test, indicating that the
      method could not securely confirm the presence/absence of particles in the
      samples. The inter-rater agreement coefficients indicated fair to moderate
      agreement between the inspectors. CONCLUSIONS: The validity and reliability were
      not satisfactory for either of the light sources. The visual detection limit
      seemed to be around 5 MUm, although we propose that an exact detection limit is
      not that relevant for compatibility testing. Based on the current findings, the
      visual examination method cannot be recommended as the sole method for judging
      compatibility of parenteral nutrition and drugs, but rather in a program of
      several methods. In the hospital pharmacy, the method may be a resource, together
      with theoretical considerations, in situations where other methods are
      unavailable; however, use of in-line-filters is essential to protect the patient.
      LAY ABSTRACT: Many patients under intensive care are in need of several
      intravenous drugs simultaneously. These drugs cannot be given in the same
      infusion line unless compatibility has been documented. Incompatibilities can
      result in, for example, precipitation of particles. Injected particles can harm
      the patient and should be avoided. Visual screening of blends of drugs for
      possible incompatibility, using a focused light source to enhance visual
      detection based on the Tyndall effect, could be a quick and easy methodology to
      identify incompatibility. In the following study the objective was to investigate
      how reliable visual inspection, with the utilization of the Tyndall effect, is at
      detecting particles and precipitations in blends of intravenous drugs and
      parenteral nutrition mixtures. Twenty inspectors each examined 20 different
      samples with two different light sources. Some of the samples were without
      particles (clean), and some contained different types and degrees of particle
      contamination. The inspectors' judgment of the samples was recorded and validity
      and reliability parameters were calculated to evaluate the method's suitability.
      The conclusion was that because of false positive and negative findings the
      visual inspection method alone is not enough to securely document
      compatibility/incompatibility, but it is more suitable as support together with
      additional methods.

PMID- 25868994
TI  - Mixing monoclonal antibody formulations using bottom-mounted mixers: impact of
      mechanism and design on drug product quality.
AB  - Using bottom-mounted mixers, particularly those that are magnetically driven, is
      becoming increasingly common during the mixing process in pharmaceutical and
      biotechnology manufacturing because of their associated low risk of
      contamination, ease of use, and ability to accommodate low minimum mixing
      volumes. Despite these benefits, the impact of bottom-mounted mixers on biologic
      drug product is not yet fully understood and is scarcely reported. This study
      evaluated four bottom-mounted mixers to assess their impact on monoclonal
      antibody formulations. Changes in product quality (size variants, particles, and
      turbidity) and impact on process performance (sterile filtration) were evaluated
      after mixing. The results suggested that mixers that are designed to function
      with no contact between the impeller and the drive unit are the most favorable
      and gentle to monoclonal antibody molecules. Designs with contact or a narrow
      clearance tended to shear and grind the protein and resulted in high particle
      count in the liquid, which would subsequently foul a filter membrane during
      sterile filtration using a 0.22 MUm pore size filter. Despite particle formation,
      increases in turbidity of the protein solution and protein
      aggregation/fragmentation were not detected. Further particle analysis indicated
      particles in the range of 0.2-2 MUm are responsible for filter fouling. A small
      scale screening model was developed using two types of magnetic stir bars
      mimicking the presence or absence of contact between the impeller and drive unit
      in the bottom-mounted mixers. The model is capable of differentiating the
      sensitivity of monoclonal antibody formulations to bottom-mounted mixers with a
      small sample size. This study fills an important gap in understanding a critical
      bioprocess unit operation. LAY ABSTRACT: Mixing is an important unit operation in
      drug product manufacturing for compounding (dilution, pooling, homogenization,
      etc.). The current trend in adopting disposable bottom-mounted mixers has raised
      concerns about their impact on drug product quality and process performance.
      However, investigations into the effects of their use for biopharmaceutical
      products, particularly monoclonal antibody formulations, are rarely published.
      The purpose of this study is three-fold: (1) to understand the impact of bottom
      mounted disposable mixer design on drug product quality and process performance,
      (2) to identify the mixing mechanism that is most gentle to protein particle
      formation, (3) to apply the learning to practical mixing operations using bottom
      mounted mixers. The outcomes of this study will benefit scientists and engineers
      who develop biologic product manufacturing process by providing a better
      understanding of mixing principles and challenges.

PMID- 25868995
TI  - In vitro analysis of the effect of in-line 1.2 micron filters on two formulations
      of propofol (2,6-diisopropyl phenol).
AB  - Recent evidence has shown improved outcomes in pediatric intensive care units
      with the intensive use of intravenous in-line filtration. This has caused
      resurgence in interest in filter use but has raised questions in relation to
      emulsion-based formulations such as propofol. Our objective was to test two
      propofol products, Diprivan((r)) and Fresofol((r)), with the Pall Lipipor((r))
      TNA and Lipipor NLF intravenous in-line filters and to assay the content before
      and after filtration under typical infusion conditions. The propofol emulsions
      were delivered from a 50 mL syringe through an extension set and into either a
      Lipipor TNA (50 mL/h(-1)) or Lipipor NLF (20 mL/h(-1)) filter. Samples were taken
      at regular intervals and assayed using a high-performance liquid chromatography
      method before and after filtration. No evidence was found of a significant
      concentration change during passage of either product through either model of
      filter. Propofol from two products was found to pass through two different types
      of Pall 1.2 MUm intravenous in-line filters. There was no significant change in
      concentration before and after filtration under typical conditions of
      administration. In conclusion, administration of these products through these
      models of in-line filter would be safe and effective.

PMID- 25868996
TI  - Evaluation of the Effect of the Volume Throughput and Maximum Flux of Low-Surface
      Tension Fluids on Bacterial Penetration of 0.2 Micron-Rated Filters during
      Process-Specific Filter Validation Testing.
AB  - Approximately 97% of filter validation tests result in the demonstration of
      absolute retention of the test bacteria, and thus sterile filter validation
      failure is rare. However, while Brevundimonas diminuta (B. diminuta) penetration
      of sterilizing-grade filters is rarely detected, the observation that some fluids
      (such as vaccines and liposomal fluids) may lead to an increased incidence of
      bacterial penetration of sterilizing-grade filters by B. diminuta has been
      reported. The goal of the following analysis was to identify important drivers of
      filter validation failure in these rare cases. The identification of these
      drivers will hopefully serve the purpose of assisting in the design of commercial
      sterile filtration processes with a low risk of filter validation failure for
      vaccine, liposomal, and related fluids. Filter validation data for low-surface
      tension fluids was collected and evaluated with regard to the effect of bacterial
      load (CFU/cm(2)), bacterial load rate (CFU/min/cm(2)), volume throughput
      (mL/cm(2)), and maximum filter flux (mL/min/cm(2)) on bacterial penetration. The
      data set (~1162 individual filtrations) included all instances of process
      specific filter validation failures performed at Pall Corporation, including
      those using other filter media, but did not include all successful retentive
      filter validation bacterial challenges. It was neither practical nor necessary to
      include all filter validation successes worldwide (Pall Corporation) to achieve
      the goals of this analysis. The percentage of failed filtration events for the
      selected total master data set was 27% (310/1162). Because it is heavily weighted
      with penetration events, this percentage is considerably higher than the actual
      rate of failed filter validations, but, as such, facilitated a close examination
      of the conditions that lead to filter validation failure. In agreement with our
      previous reports, two of the significant drivers of bacterial penetration
      identified were the total bacterial load and the bacterial load rate. In addition
      to these parameters, another three possible drivers of failure were also
      identified: volume throughput, maximum filter flux, and pressure. Of the data for
      which volume throughput information was available, 24% (249/1038) of the
      filtrations resulted in penetration. However, for the volume throughput range of
      680-2260 mL/cm(2), only 9 out of 205 bacterial challenges (~4%) resulted in
      penetration. Of the data for which flux information was available, 22% (212/946)
      resulted in bacterial penetration. However, in the maximum filter flux range from
      7 to 18 mL/min/cm(2), only one out of 121 filtrations (0.6%) resulted in
      penetration. A slight increase in filter failure was observed in filter bacterial
      challenges with a differential pressure greater than 30 psid. When designing a
      commercial process for the sterile filtration of a low-surface-tension fluid (or
      any other potentially high-risk fluid), targeting the volume throughput range of
      680-2260 mL/cm(2) or flux range of 7-18 mL/min/cm(2), and maintaining the
      differential pressure below 30 psid, could significantly decrease the risk of
      validation filter failure. However, it is important to keep in mind that these
      are general trends described in this study and some test fluids may not conform
      to the general trends described here. Ultimately, it is important to evaluate
      both filterability and bacterial retention of the test fluid under proposed
      process conditions prior to finalizing the manufacturing process to ensure
      successful process-specific filter validation of low-surface-tension fluids. LAY
      ABSTRACT: An overwhelming majority of process-specific filter validation
      (qualification) tests result in the demonstration of absolute retention of test
      bacteria by sterilizing-grade membrane filters. As such, process-specific filter
      validation failure is rare. However, while bacterial penetration of sterilizing
      grade filters during process-specific filter validation is rarely detected, some
      fluids (such as vaccines and liposomal fluids) have been associated with an
      increased incidence of bacterial penetration. The goal of the following analysis
      was to identify important drivers of process-specific filter validation failure.
      The identification of these drivers will possibly serve to assist in the design
      of commercial sterile filtration processes with a low risk of filter validation
      failure. Filter validation data for low-surface-tension fluids was collected and
      evaluated with regard to bacterial concentration and rates, as well as filtered
      fluid volume and rate (Pall Corporation). The master data set (~1160 individual
      filtrations) included all recorded instances of process-specific filter
      validation failures but did not include all successful filter validation
      bacterial challenge tests. This allowed for a close examination of the conditions
      that lead to process-specific filter validation failure. As previously reported,
      two significant drivers of bacterial penetration were identified: the total
      bacterial load (the total number of bacteria per filter) and the bacterial load
      rate (the rate at which bacteria were applied to the filter). In addition to
      these parameters, another three possible drivers of failure were also identified:
      volumetric throughput, filter flux, and pressure. When designing a commercial
      process for the sterile filtration of a low-surface-tension fluid (or any other
      penetrative-risk fluid), targeting the identified bacterial challenge loads,
      volume throughput, and corresponding flux rates could decrease, and possibly
      eliminate, the risk of validation filter failure. However, it is important to
      keep in mind that these are general trends described in this study and some test
      fluids may not conform to the general trends described here. Ultimately, it is
      important to evaluate both filterability and bacterial retention of the test
      fluid under proposed process conditions prior to finalizing the manufacturing
      process to ensure successful filter validation of low-surface-tension fluids.

PMID- 25868997
TI  - PDA Single-Use Systems Cross-Organizational Workshop-Meeting Summary, May 14,
      2014-PDA Global Headquarters, Bethesda, MD.
AB  - The application of single-use systems, or disposables, has increased dramatically
      in the past 10 years. Although some elements of the pharmaceutical and biotech
      manufacturing process were single-use and therefore disposable and not reused,
      the majority of the process equipment and fluid path was cleaned and reused by
      end users. Today, much more of the manufacturing process is composed of single
      use systems, and there are some biotech plants that use single-use systems
      exclusively. Because of this increasing reliance on suppliers, there is an urgent
      need for more formal standards specifically for single-use system technology. The
      objective of this PDA-sponsored workshop held on May 14, 2014 was twofold: (1) to
      promote a harmonized approach to supporting single-use system activities within
      the industry and in so doing to minimize duplication of efforts, and (2) to
      communicate ongoing single-use system initiatives among the group.
      Representatives of ASME, ASTM, BPOG, BPSA, ELSIE, PDA, PQRI, and USP, as well as
      representatives of CBER and CDER of FDA, attended. LAY ABSTRACT: Today, the
      majority of pharmaceutical and biotech drug manufacturing equipment is cleaned
      and reused. However, in the past 10 years, the use of disposable manufacturing
      systems has increased dramatically; there are even some biotech-derived drugs
      that are manufactured entirely using single-use technology. This movement toward
      disposables has placed increased reliance on disposable equipment suppliers, each
      of which manufactures its products independently to meet customer needs. This
      fact has led to non-uniformity in design for connectors and similar sub
      processes, and has made the need for more formal industry standards. The
      objective of this PDA-sponsored workshop held on May 14, 2014 was twofold: (1) to
      promote a harmonized approach to supporting single-use system projects within the
      industry and in so doing to minimize duplication of efforts, and (2) to
      communicate ongoing single-use system initiatives among the group.
      Representatives of industry associations and standard-setting organizations, as
      well as representatives of the U.S. Food and Drug Administration, attended.

PMID- 25868998
TI  - Knowledge Management and ICH.

PMID- 25868999
TI  - The CRISPR-Cas immune system: biology, mechanisms and applications.
AB  - Viruses are a common threat to cellular life, not the least to bacteria and
      archaea who constitute the majority of life on Earth. Consequently, a variety of
      mechanisms to resist virus infection has evolved. A recent discovery is the
      adaptive immune system in prokaryotes, a type of system previously thought to be
      present only in vertebrates. The system, called CRISPR-Cas, provide sequence
      specific adaptive immunity and fundamentally affect our understanding of virus
      host interaction. CRISPR-based immunity acts by integrating short virus sequences
      in the cell's CRISPR locus, allowing the cell to remember, recognize and clear
      infections. There has been rapid advancement in our understanding of this immune
      system and its applications, but there are many aspects that await elucidation
      making the field an exciting area of research. This review provides an overview
      of the field and highlights unresolved issues. 

PMID- 25869001
TI  - Ribosomal proteomics: Strategies, approaches, and perspectives.
AB  - Over the past few decades, proteomic research has seen unprecedented development
      due to technological advancement. However, whole-cell proteomics still has
      limitations with respect to sample complexity and the accuracy of determining
      protein locations. To deal with these limitations, several subcellular proteomic
      studies have been initiated. Nevertheless, compared to other subcellular
      proteomic fields, such as mitochondrial proteomics, ribosomal proteomics has
      lagged behind due to the long-held idea that the ribosome is just a translation
      machine. Recently, with the proposed ribosome filter hypothesis and subsequent
      studies of ribosome-specific regulatory capacity, ribosomal proteomics has become
      a promising chapter for both proteomic and ribosomal research. In this review, we
      discuss the current strategies and approaches in ribosomal proteomics and the
      efficacies as well as disadvantages of individual approaches for further
      improvement. 

PMID- 25869000
TI  - Origin and evolution of metabolic sub-cellular compartmentalization in
      eukaryotes.
AB  - A high level of subcellular compartmentalization is a hallmark of eukaryotic
      cells. This intricate internal organization was present already in the common
      ancestor of all extant eukaryotes, and the determination of the origins and early
      evolution of the different organelles remains largely elusive. Organellar
      proteomes are determined through regulated pathways that target proteins produced
      in the cytosol to their final subcellular destinations. This internal sorting of
      proteins can vary across different physiological conditions, cell types and
      lineages. Evolutionary retargeting - the alteration of a subcellular localization
      of a protein in the course of evolution - has been rampant in eukaryotes and
      involves any possible combination of organelles. This fact adds another layer of
      difficulty to the reconstruction of the origins and evolution of organelles. In
      this review we discuss current themes in relation to the origin and evolution of
      organellar proteomes. Throughout the text, a special focus is set on the
      evolution of mitochondrial and peroxisomal proteomes, which are two organelles
      for which extensive proteomic and evolutionary studies have been performed. 

PMID- 25869003
TI  - Human immunodeficiency virus-associated pulmonary arterial hypertension:
      considerations for pulmonary vascular diseases in the developing world.

PMID- 25869002
TI  - Human iPSC-Derived Neural Progenitors Preserve Vision in an AMD-Like Model.
AB  - Pluripotent stem cell-derived retinal pigment epithelial (RPE) cells are
      currently being tested for cell replacement in late-stage age-related macular
      degeneration (AMD). However, preserving vision at early-stages may also be
      possible. Here, we demonstrate that transplantation of neural progenitor cells
      (NPCs) derived from induced pluripotent stem cells (iNPCs) limits disease
      progression in the Royal College of Surgeons rat, a preclinical model of AMD.
      Grafted-iNPCs survived, remained undifferentiated, and distributed extensively in
      a laminar fashion in the subretinal space. Retinal pathology resulting from the
      accumulation of undigested photoreceptor outer segments (POS) was significantly
      reduced in iNPC-injected rats compared with controls. Phagosomes within grafted
      iNPCs contained POS, suggesting that iNPCs had compensated for defective POS
      phagocytosis by host-RPE. The iNPC-treated eyes contained six to eight rows of
      photoreceptor nuclei that spanned up to 5 mm in length in transverse retinal
      sections, compared with only one row of photoreceptors in controls. iNPC
      treatment fully preserved visual acuity measured by optokinetic response.
      Electrophysiological recordings revealed that retina with the best iNPC-protected
      areas were 140-fold more sensitive to light stimulation than equivalent areas of
      contralateral eyes. The results described here support the therapeutic utility of
      iNPCs as autologous grafts for early-stage of AMD.

PMID- 25869005
TI  - Coronary bones.

PMID- 25869006
TI  - Left aortic arch, right descending aorta, and right patent ductus arteriosus:
      precise depiction of a rare vascular ring with cardiac computed tomography.

PMID- 25869007
TI  - Letter by Le Faucheur et al regarding articles, "Six-minute walk is a better
      outcome measure than treadmill walking tests in therapeutic trials of patients
      with peripheral artery disease" and "The treadmill is a better functional test
      than the 6-minute walk test in therapeutic trials of patients with peripheral
      artery disease".

PMID- 25869009
TI  - Correction.
AB  - In the article by Smith et al, "AHA/ACCF Secondary Prevention and Risk Reduction
      Therapy for Patients With Coronary and Other Atherosclerotic Vascular Disease:
      2011 Update: A Guideline From the American Heart Association and American College
      of Cardiology Foundation," which published online November 3, 2011, and appeared
      with the November 29, 2011, issue of the journal (Circulation. 2011;124:2458
      2473. DOI: 10.1161/CIR.0b013e318235eb4d.), several corrections were needed. The
      authors regret the errors. These corrections have been made to the current online
      version of the article, which is available at
      http://circ.ahajournals.org/content/124/22/2458.

PMID- 25869008
TI  - Response to letter regarding article, "Six-minute walk is a better outcome
      measure than treadmill walking tests in therapeutic trials of patients with
      peripheral artery disease".

PMID- 25869010
TI  - Comparing Facial 3D Analysis With DNA Testing to Determine Zygosities of Twins.
AB  - The aim of this study was to compare facial 3D analysis to DNA testing in twin
      zygosity determinations. Facial 3D images of 106 pairs of young adult Lithuanian
      twins were taken with a stereophotogrammetric device (3dMD, Atlanta, Georgia) and
      zygosity was determined according to similarity of facial form. Statistical
      pattern recognition methodology was used for classification. The results showed
      that in 75% to 90% of the cases, zygosity determinations were similar to DNA
      based results. There were 81 different classification scenarios, including 3
      groups, 3 features, 3 different scaling methods, and 3 threshold levels. It
      appeared that coincidence with 0.5 mm tolerance is the most suitable feature for
      classification. Also, leaving out scaling improves results in most cases. Scaling
      was expected to equalize the magnitude of differences and therefore lead to
      better recognition performance. Still, better classification features and a more
      effective scaling method or classification in different facial areas could
      further improve the results. In most of the cases, male pair zygosity recognition
      was at a higher level compared with females. Erroneously classified twin pairs
      appear to be obvious outliers in the sample. In particular, faces of young
      dizygotic (DZ) twins may be so similar that it is very hard to define a feature
      that would help classify the pair as DZ. Correspondingly, monozygotic (MZ) twins
      may have faces with quite different shapes. Such anomalous twin pairs are
      interesting exceptions, but they form a considerable portion in both zygosity
      groups. 

PMID- 25869011
TI  - Limited clinical utility of genotype-guided warfarin initiation dosing algorithms
      versus standard therapy: a meta-analysis and trial sequential analysis of 11
      randomized controlled trials.
AB  - In terms of inconsistent conclusions across all relevant randomized controlled
      trials (RCTs) and available meta-analyses, we aimed to use a meta-analysis and
      trial sequential analysis (TSA) to evaluate whether clinical utility of a
      genotype-guided warfarin initiation dosing algorithm could be better than that of
      a standard therapy regimen, and whether currently relevant evidence could be
      reliable and conclusive. Overall, 11 eligible RCTs involving 2677 patients were
      included for further analyses. Compared with fixed dose or clinically adjusted
      warfarin initiation dosing regimens, genotype-guided algorithms significantly
      increased time in therapeutic range, shortened time to first therapeutic
      international normalized ratio (INR) and time to stable doses, but did not show
      any marked improvements in excessive anticoagulation, bleeding events,
      thromboembolism, or all-cause mortality. Subgroup analyses revealed that,
      genotype-guided algorithms showed better control in the outcomes of time in
      therapeutic range or excessive anticoagulation than fixed-dose regimens rather
      than clinically adjusted regimens. Except for excessive anticoagulation,
      currently available evidence of all other outcomes was unreliable and
      inconclusive as determined with TSA. Our findings suggest that genotype-guided
      warfarin initiation dosing algorithms have superiority in the improvement of
      surrogate quality markers for anticoagulation control, but that this does not
      translate into statistically significant differences in clinical outcomes, which
      is largely because of the insufficient sample size in the RCTs analyzed. 

PMID- 25869012
TI  - The P2 promoter of the IGF1 gene is a major epigenetic locus for GH
      responsiveness.
AB  - Short children using growth hormone (GH) to accelerate their growth respond to
      this treatment with a variable efficacy. The causes of this individual
      variability are multifactorial and could involve epigenetics. Quantifying the
      impact of epigenetic variation on response to treatments is an emerging
      challenge. Here we show that methylation of a cluster of CGs located within the
      P2 promoter of the insulin-like growth factor 1 (IGF1) gene, notably CG-137, is
      inversely closely correlated with the response of growth and circulating IGF1 to
      GH administration. For example, variability in CG-137 methylation contributes 25%
      to variance of growth response to GH. Methylation of CGs in the P2 promoter is
      negatively associated with the increased transcriptional activity of P2 promoter
      in patients' mononuclear blood cells following GH administration. Our observation
      indicates that epigenetics is a major determinant of GH signaling (physiology)
      and of individual responsiveness to GH treatment (pharmacoepigenetics). 

PMID- 25869013
TI  - A non-synonymous polymorphism in galectin-3 lectin domain is associated with
      allergic reactions to beta-lactam antibiotics.
AB  - Genetic predictors of beta-lactam (BL) allergy are mostly related to
      Immunoglobulin E (IgE) synthesis and atopy. Despite this context, little
      attention has been devoted to genes of IgE/FcERI pathway, such as galectin-3, a
      beta-galactoside-binding lectin, which binds to IgE. We evaluated the association
      of LGALS3 polymorphisms with BL allergy in 395 Spanish and 198 Italian cases,
      compared with 310- and 339-matched controls, respectively. The rs11125 predicted
      BL allergy with an odds ratio of 4.0 in Spanish population (P<0.0001). This
      association was replicated with an odds ratio of 5.1 in Italian population
      (P<0.0001); rs11125 predicted also increased serum level of total IgE in Spanish
      controls. These data are consistent with the predicted deleterious influence of
      Gln>His substitution produced by rs11125 on galactose-binding activity of
      galectin-3. In conclusion, LGALS3 is the strongest genetic predictor of BL
      allergy reported so far. This association reflects the influence of genes of
      IgE/FcERI pathway in this pathology. 

PMID- 25869014
TI  - Unravelling the transcriptomic landscape of the major phase II UDP
      glucuronosyltransferase drug metabolizing pathway using targeted RNA sequencing.
AB  - A comprehensive view of the human UDP-glucuronosyltransferase (UGT) transcriptome
      is a prerequisite to the establishment of an individual's UGT metabolic
      glucuronidation signature. Here, we uncover the transcriptome landscape of the 10
      human UGT gene loci in normal and tumoral metabolic tissues by targeted RNA next
      generation sequencing. Alignment on the human hg19 reference genome identifies
      234 novel exon-exon junctions. We recover all previously known UGT1 and UGT2
      enzyme-coding transcripts and identify over 130 structurally and functionally
      diverse novel UGT variants. We further expose a revised genomic structure of UGT
      loci and provide a comprehensive repertoire of transcripts for each UGT gene.
      Data also uncover a remodelling of the UGT transcriptome occurring in a tissue-
      and tumor-specific manner. The complex alternative splicing program regulating
      UGT expression and protein functions is likely critical in determining
      detoxification capacity of an organ and stress-related responses, with
      significant impact on drug responses and diseases. 

PMID- 25869016
TI  - Abstracts from the 38th annual meeting of the society of general internal
      medicine.

PMID- 25869015
TI  - Clinical validity of new genetic biomarkers of irinotecan neutropenia: an
      independent replication study.
AB  - The overall goal of this study was to provide evidence for the clinical validity
      of nine genetic variants in five genes previously associated with irinotecan
      neutropenia and pharmacokinetics. Variants associated with absolute neutrophil
      count (ANC) nadir and/or irinotecan pharmacokinetics in a discovery cohort of
      cancer patients were genotyped in an independent replication cohort of 108 cancer
      patients. Patients received single-agent irinotecan every 3 weeks. For ANC nadir,
      we replicated UGT1A1*28, UGT1A1*93 and SLCO1B1*1b in univariate analyses. For
      irinotecan area under the concentration-time curve (AUC0-24), we replicated ABCC2
      -24C>T; however, ABCC2 -24C>T only predicted a small fraction of the variance.
      For SN-38 AUC0-24 and the glucuronidation ratio, we replicated UGT1A1*28 and
      UGT1A1*93. In addition to UGT1A1*28, this study independently validated UGT1A1*93
      and SLCO1B1*1b as new predictors of irinotecan neutropenia. Further demonstration
      of their clinical utility will optimize irinotecan therapy in cancer patients. 

PMID- 25869018
TI  - Medical Residents and Interprofessional Interactions in Discharge: An
      Ethnographic Exploration of Factors That Affect Negotiation.
AB  - BACKGROUND: Interprofessional collaboration is an important aspect of patient
      discharge from a general internal medicine (GIM) unit. However, there has been
      minimal empirical or theoretical research that has examined interactions that
      occur between medical residents and other healthcare professionals in the
      discharge process. This study provides insight into the social processes that
      shape and characterize such interactions. OBJECTIVE: To explore factors that
      shape interactions between medical residents and other healthcare professionals
      in relation to patient discharge, and to examine the opportunities for
      negotiations about discharge between these professional groups. DESIGN: A
      qualitative ethnographic approach using observations, interviews and documentary
      analysis. PARTICIPANTS AND SETTING: Healthcare professionals working in a GIM
      unit in Canada. APPROACH: Sixty-five hours of observations were undertaken in a
      range of settings (e.g. interprofessional rounds, medical and nursing rounds,
      nursing station) in the unit over a 17-month period. A maximum variation sampling
      approach was used to identify healthcare professionals working in the unit.
      Twenty-three interviews were completed, recorded and transcribed verbatim. A
      directed content approach using theories of medical dominance and negotiated
      order was used to analyze the data. KEY RESULTS: The organization of clinical
      work in combination with clinical teaching influenced interprofessional
      interactions and the quality of discharge in this GIM unit. While organizational
      activities (orientation and rounds) and individual activities (e.g. role
      modeling, teaching) supported negotiations between medical residents and other
      healthcare professionals around discharge, participants had varied perspectives
      about their effectiveness. CONCLUSIONS: This study illuminates social factors and
      processes that require attention in order to address challenges with
      interprofessional collaboration and discharge in GIM. These findings have
      implications for medical education, workplace learning, patient safety and
      quality improvement.

PMID- 25869017
TI  - Adult Patients' Perspectives on the Benefits and Harms of Overused Screening
      Tests: a Qualitative Study.
AB  - BACKGROUND: In recent years, there has been a growing interest in reducing the
      overuse of healthcare services. However, little is known about how patients
      conceptualize the benefits and harms of overused screening tests or how patients
      make decisions regarding these tests. OBJECTIVE: To determine how patients think
      about the harms and benefits of overused screening tests and how they consider
      these and other factors when making decisions. DESIGN: Semi-structured,
      qualitative interviews. PARTICIPANTS: The study comprised 50 patients, ages 50
      84, who had previously received or not received any of four overused screening
      services: 1) prostate cancer screening (men ages 50-69), 2) colon cancer
      screening (men and women ages 76-85), 3) osteoporosis screening (low-risk women
      ages 50-64), or 4) cardiovascular disease screening (low-risk men and women ages
      50-85). APPROACH: We conducted a thematic analysis, using a hybrid inductive
      deductive approach. Two independent coders analyzed interview transcriptions to
      identify themes and exemplifying quotes. KEY RESULTS: Many patients could not
      name a harm of screening. When they did name harms, patients often focused on
      only the harms of the screening test itself and rarely mentioned harms further
      along the screening cascade (e.g., from follow-up testing and treatment). In
      contrast, patients could easily name benefits of screening, although many seemed
      to misunderstand or overestimate the magnitude of the benefits. Furthermore,
      patients described many additional factors they considered when making screening
      decisions, including their clinicians' recommendations, their age, family or
      friends' experiences with disease, and insurance coverage. CONCLUSIONS: This
      study highlights the need to help adults recognize and understand the benefits
      and harms of screening and make appropriate decisions about overused screening
      tests.

PMID- 25869019
TI  - An Often-Overlooked Etiology of Pleuritic Chest Pain.

PMID- 25869020
TI  - Pending Studies at Hospital Discharge.

PMID- 25869021
TI  - KLF15 in breast cancer: a novel tumor suppressor?
AB  - PURPOSE: Kruppel-like factor 15 (KLF15) is a transcription factor that is
      involved in various biological processes, including cellular proliferation,
      differentiation and death. In addition, KLF15 has recently been implicated in the
      development of several human malignancies, including breast cancer. In vitro
      breast cancer studies have pointed at a putative role in the regulation of cell
      proliferation. As yet, however, KLF15 expression analyses in primary human breast
      cancers have not been reported. Here, we set out to investigate the clinical and
      biological significance of KLF15 expression in human breast cancers. METHODS:
      KLF15 expression was evaluated by immunohistochemistry in 54 primary invasive
      ductal breast carcinomas, and its status was correlated with various
      clinicopathological parameters. We also assessed KLF15 expression in vitro in 4
      breast cancer-derived cell lines using Western blotting, and examined the effects
      of exogenous KLF15 expression on cell cycle progression using flow cytometry.
      Concomitant (changes in) p21, p27 and TOPO2A expression levels were examined
      using real-time RT-PCR and immunocytochemistry, respectively. RESULTS: In ~90% of
      the primary breast carcinoma tissues tested, KLF15 was found to be expressed and
      localized in either the cytoplasm, the nucleus or both. Predominant nuclear
      immunoreactivity was found to be associated with clinicopathological factors
      predicting a better clinical outcome (i.e., ER positive, HER2 negative, low
      grade, low Ki-67 expression). The breast cancer-derived cell lines tested showed
      a low KLF15 expression with a predominant cytoplasmic localization. Subsequent
      exogenous KLF15 over-expression resulted in a predominant nuclear localization
      and a concomitant decreased cellular proliferation and an arrest at the G0/G1
      phase of the cell cycle. In addition, we found that nuclear KLF15 expression
      results in up-regulation of p21, a pivotal suppressor of the G1 to S phase
      transition of the cell cycle. CONCLUSIONS: Our results indicate that nuclear
      KLF15 expression suppresses breast cancer cell proliferation at least partially
      through p21 up-regulation and subsequent cell cycle arrest. This is a first study
      addressing the role of KLF15 in breast cancer development.

PMID- 25869022
TI  - A fresh frozen plasma to red blood cell transfusion ratio of 1:1 mitigates lung
      injury in a rat model of damage control resuscitation for hemorrhagic shock.
AB  - BACKGROUND: We aimed to evaluate the effects of resuscitation with different
      ratios of fresh frozen plasma (FFP) to red blood cells (RBCs) on pulmonary
      inflammatory injury and to illuminate the beneficial effects of FFP on lung
      protection compared with lactated ringers (LR) using a rat model of hemorrhagic
      shock. METHODS: Rats underwent pressure-controlled hemorrhage for 60 minutes and
      were then transfused with LR for initial resuscitation. Thereafter, the rats were
      transfused with varying ratios of FFP:RBC (1:4, 1:2, 1:1, and 2:1) or LR:RBC
      (1:1) to hold their mean arterial pressure (MAP) at 100 +/- 3 mm Hg for 30
      minutes. After 4 hours of observation, lung tissue was harvested to determine the
      wet/dry weight, myeloperoxidase levels, tumor necrosis factor alpha levels,
      macrophage inflammatory protein 2 (MIP-2) levels, inducible nitric oxide synthase
      activity, and the nuclear factor kappaB p65 DNA-binding activity. RESULTS: With
      an increase in the FFP:RBC ratio, the volume of required RBC to maintain the
      target MAP decreased. The MAP value in each group was not significantly different
      during the whole experiment period. The values of the wet/dry weights and MIP-2
      were significantly lower in the FFP:RBC = 1:1 group than the other groups (P <
      .05). All parameters detected above were predominantly lower in the FFP:RBC = 1:1
      group than the FFP:RBC = 1:2 group and the LR:RBC = 1:1 group (P < .05). In
      addition, all parameter values were lower in the FFP:RBC = 1:1 group than in the
      FFP:RBC = 2:1 group, but only the wet/dry weight, myeloperoxidase, and MIP-2
      values were significantly different (P < .05). CONCLUSIONS: Resuscitation with a
      1:1 ratio of FFP to RBC results in decreased lung inflammation. Compared with LR,
      FFP could further mitigate lung inflammatory injury.

PMID- 25869023
TI  - Treatment strategies for prosthetic valve thrombosis in pregnant patients.

PMID- 25869024
TI  - Effect of superficial cervical plexus block on postoperative quality of recovery
      after anterior cervical discectomy and fusion: a randomized controlled trial.
AB  - PURPOSE: Spine surgeries are increasingly being performed as a day or short-stay
      surgery programs. Peripheral nerve block provide site-specific pain relief with
      few side effects, thereby reducing surgical stress and enhancing quality of
      recovery. The aim of our study was to determine the effect of a superficial
      cervical plexus block (SCPB) on postoperative quality of recovery and analgesia
      in patients undergoing elective anterior cervical discectomy and fusion (ACDF).
      METHODS: After Research Ethics Board approval, we enrolled adults (> 18 yr)
      scheduled for elective single- or two-level ACDF in this randomized double-blind
      clinical trial. Participants were randomized to receive either a SCPB (0.25%
      bupivacaine, 10 mL) or No Block. The primary outcome measure was the quality of
      recovery at 24 hr, measured using the 40-item quality of recovery questionnaire
      (QoR-40). In addition, comparisons between groups were also made for
      postoperative opioid consumption and discharge times. RESULTS: Forty-six patients
      were randomized to receive either a SCPB block (n = 23) or No Block (n = 23).
      Median [interquartile range] aggregated global QoR-40 scores at 24 hr were
      significantly greater in the SCPB group, indicating good quality of recovery
      compared with the No Block group (179 [116-195] vs 157 [97-196], respectively;
      median difference, 22; 95% confidence interval [CI], 7 to 34; P = 0.002]. There
      were no differences between the SCPB and the No Block group with regard to mean
      (standard deviation) postoperative opioid consumption at 24 hr [22.9 (13.6) mg vs
      24.6 (9.5) mg, respectively; mean difference 1.7; 95% CI, -5.2 to 8.7; P = 0.620]
      and the number of patients discharged within 24 hr (15 vs 12, respectively; P =
      0.550). CONCLUSION: We showed that preoperative SCPB is an effective strategy for
      improving the early quality of recovery in patients undergoing single- or two
      level ACDF. Nevertheless, there was no impact on opioid consumption or discharge
      times. This trial was registered at www.clinicaltrials.gov (NCT01662219).

PMID- 25869025
TI  - The impact of two different inspiratory to expiratory ratios (1:1 and 1:2) on
      respiratory mechanics and oxygenation during volume-controlled ventilation in
      robot-assisted laparoscopic radical prostatectomy: a randomized controlled trial.
AB  - BACKGROUND: Volume-controlled ventilation with a prolonged inspiratory to
      expiratory ratio (I:E ratio) has been used to optimize gas exchange and
      respiratory mechanics in various surgical settings. We hypothesized that, when
      compared with an I:E ratio of 1:2, a prolonged I:E ratio of 1:1 would improve
      respiratory mechanics without reducing cardiac output (CO) during
      pneumoperitoneum and steep Trendelenburg positioning, both of which can impair
      respiratory function in robot-assisted laparoscopic radical prostatectomy.
      Furthermore, we evaluated its effect on oxygenation during robot-assisted
      laparoscopic radical prostatectomy. METHODS: Eighty patients undergoing robot
      assisted laparoscopic radical prostatectomy were randomly allocated to receive an
      I:E ratio of either 1:1 (group 1:1) or 1:2 (group 1:2). The primary endpoint,
      peak airway pressure (Ppeak), as well as hemodynamic data, including cardiac
      output (CO) and arterial oxygen tension (PaO2), were compared between groups at
      four time points: ten minutes after anesthesia induction (T1), 30 and 60 min
      after pneumoperitoneum with steep Trendelenburg positioning (T2 and T3), and ten
      minutes after supine positioning (T4). Overall comparisons were made between
      groups using linear mixed model analysis with post hoc testing of individual time
      points adjusted using a Bonferroni correction. RESULTS: Linear mixed model
      analysis showed a significant overall difference in Ppeak between the two groups
      (P < 0.001). Post hoc analysis showed a significantly lower mean (SD) Ppeak in
      group 1:1 than in group 1:2 at T2 [28.4 (4.0) cm H2O vs 32.8 (5.2) cm H2O,
      respectively; mean difference, 4.3 cm H2O; 95% confidence interval (CI), 2.3 to
      6.4; P < 0.001] and T3 [27.8 (3.9) cm H2O vs 32.6 (5.0) cm H2O, respectively;
      mean difference, 4.7 cm H2O; 95% CI, 2.7 to 6.7; P < 0.001]. The CO assessed over
      these time points was comparable in both groups (P = 0.784). In addition, there
      were no significant differences in PaO2 between the two groups (P = 0.521).
      CONCLUSIONS: Compared with an I:E ratio of 1:2, a ratio of 1:1 lowered Ppeak
      without reducing CO during pneumoperitoneum and steep Trendelenburg positioning.
      Nevertheless, our results did not support its use solely for improving
      oxygenation. This trial was registered at http://clinicaltrials.gov/
      (NCT01892449).

PMID- 25869026
TI  - Nanoparticles coated with the tumor-penetrating peptide iRGD reduce experimental
      breast cancer metastasis in the brain.
AB  - Metastasis is the main killer in cancer; consequently, there is great interest in
      novel approaches to prevent and treat metastatic disease. Brain metastases are
      particularly deadly, as the protection of the blood-brain barrier obstructs the
      passage of common anticancer drugs. This study used magnetic resonance imaging
      (MRI) to investigate the therapeutic effects of nanoparticles coated with a tumor
      penetrating peptide (iRGD) against a preclinical model of breast cancer brain
      metastasis. Single doses of iRGD nanoparticle were administered intravenously,
      and the effect on tumor growth was observed over time. iRGD nanoparticles, when
      applied in the early stages of metastasis development, strongly inhibited tumor
      progression. Overall, this study demonstrated for the first time that a single
      dose of iRGD nanoparticle can have a significant effect on metastatic tumor
      progression and nonproliferative cancer cell retention when applied early in
      course of tumor development. These data suggest that iRGD nanoparticles may be
      useful in preventatively reducing metastasis after a cancer diagnosis has been
      established. KEY MESSAGES: bSSFP MRI can be used to track nonproliferative iron
      labeled cells and tumor development over time. iRGD-NW, when applied early, has a
      significant effect on metastatic tumor progression. Retained signal voids
      represent a subpopulation of nonproliferating tumor cells. Reduced cell retention
      and tumor burden show a role for iRGD-NW in metastasis prevention. iRGD target is
      universally expressed; thus, iRGD-NW should be clinically translatable.

PMID- 25869027
TI  - Factors that influence treatment decision-making in elderly DLBCL patients: a
      case vignette study.
AB  - Elderly patients with diffuse large B-cell lymphoma (DLBCL) are frequently not
      treated with standard immunochemotherapy, and this influences survival
      negatively. The purpose of this study was to gain more insight into treatment
      decision-making by hematologists. Case vignettes concerning patients with DLBCL
      were presented to hematologists in the Netherlands. Patient characteristics (age,
      comorbidity) differed per case. Respondents were asked in each case if they would
      treat the patient with curative intent by means of full-dose chemotherapy or
      chemotherapy with dose reduction or if they would not treat the patient with
      curative intent. The vast majority of respondents would treat an elderly patient
      diagnosed with DLBCL without a relevant medical history with full-dose
      chemotherapy irrespective of age. In the presence of comorbidity, lack of social
      support, cognitive disorders, and untreated depression dose reductions in advance
      are frequently applied or patients are not treated with curative intent. This is
      most pronounced for patients aged older than 80 years. Respondents working in a
      university hospital more frequently refrain form full-dose chemotherapy with
      curative intent compared to respondents working in tertiary medical teaching
      hospitals or general hospitals. Patients without a relevant medical history are
      generally treated with curative intent irrespective of age. Cognitive disorders,
      comorbidity, and depression reduce the change of being treated with curative
      intent. This is most prominent in the eldest patient category.

PMID- 25869028
TI  - The prognostic nutritional index predicts survival for patients with extranodal
      natural killer/T cell lymphoma, nasal type.
AB  - The prognostic nutritional index (PNI), an indicator of nutritional status and
      systemic inflammation, is associated with survival in several types of tumors.
      The prognostic value of the PNI in lymphoma remains unclear. The present study
      aimed to evaluate the prognostic significance of the PNI in patients with
      extranodal natural killer/T cell lymphoma, nasal type (ENKTL). This retrospective
      study in two institutions was comprised of 177 patients with newly diagnosed
      ENKTL. Patients with a combined albumin (g/L) + 5 * total lymphocyte count *
      10(9)/l >= 45 were allocated a PNI score of 0. Patients in whom this total was
      <45 were allocated a score of 1. Patients with a pretreatment PNI score of 1 had
      more adverse clinical features, lower complete remission rates (p = 0.005), and
      worse overall survival (OS, p < 0.001) and progression-free survival (p = 0.004)
      compared with those with a PNI score of 0. Multivariate analysis showed that the
      PNI (p < 0.001) and tumor mass >=5 cm (p < 0.001) were independent predictors of
      worse OS. The PNI was predictive in extranasal disease and nasal disease (both p
      < 0.05). The PNI could differentiate low-risk patients as classified according to
      the International Prognostic Index and Prognosis Index for peripheral T cell
      lymphoma scoring, as well as patients in a different category using the Korean
      Prognostic Index scores with different survival outcomes (all p < 0.05). The PNI
      is a powerful predictor of survival in ENKTL. Nutritional status and inflammatory
      responses at diagnosis might play an important role in survival in patients with
      ENKTL.

PMID- 25869029
TI  - Minimal residual disease negativity in elderly patients with acute myeloid
      leukemia may indicate different postremission strategies than in younger
      patients.
AB  - In the present analysis, we evaluated whether in elderly acute myeloid leukemia
      (AML) patients (>60 years), minimal residual disease (MRD) assessed by flow
      cytometry may have a role in guiding choice of postremission strategies. We
      analyzed 149 young and 61 elderly adults who achieved morphological CR after
      induction course of EORTC/GIMEMA protocols. Elderly patients reached a
      postconsolidation MRD negative status less frequently than younger ones (11 vs 28
      %, p = 0.009). MRD negativity resulted in a longer 5-year disease-free survival
      (DFS) both in elderly (57 vs 13 %, p = 0.0197) and in younger patients (56 vs 31
      %, p = 0.0017). Accordingly, 5-year cumulative incidence of relapse (CIR) of both
      elderly (83 vs 42 %, p = 0.045) and younger patients (59 vs 24 % p = NS) who were
      MRD positive doubled that of MRD negative ones. Nevertheless, CIR of MRD negative
      elderly patients was twofold higher than that of younger MRD negative ones (42 vs
      24 %, p = NS). In conclusion, elderly patients in whom chemotherapy yields a MRD
      negative CR have duration of DFS and rate of CIR significantly better than those
      who remain MRD positive. Nonetheless, the high CIR rate observed in the elderly
      suggests that MRD negativity might have different therapeutic implications in
      this population than in the younger counterpart. 

PMID- 25869030
TI  - Successful treatment with rivaroxaban of an extended superficial vein thrombosis
      in a patient with acquired antithrombin deficiency due to Peg-asparaginase
      treatment.

PMID- 25869031
TI  - Sense, missense, and nonsense: a novel mechanism of premature termination codon
      (PTC) mutation in a severe von Willebrand disease (VWD) patient.

PMID- 25869032
TI  - A reach-out system for video microscopy analysis of ciliary motions aiding PCD
      diagnosis.
AB  - BACKGROUNDS: High-speed Video-Microscopy Analysis (HVMA) is now being used to aid
      diagnosis of Primary Ciliary Dyskinesia (PCD). Only a few centers however, are
      equipped with the available resources and equipment to perform these tests. We
      describe our experience in HVMA reaching-out to many more peripheral and
      relatively remote areas. A portable computer with HVMA software, video camera and
      a microscope were used. Fourteen disperse pediatric centers were reached and a
      total of 203 subjects were tested within a relatively short time (Clinical Trial
      Registration: NCT 01070914 (registered February 6, 2010). RESULTS: With an
      average time of 20 minutes per patient, the system enabled us to test
      approximately 10-15 subjects per day. A valid HVMA result was made in 148
      subjects and helped in the diagnosis of PCD in many of the patients who were
      subsequently confirmed to have PCD by electron microscopy and/or
      immunofluoresence and/or genetics and/or nasal Nitric Oxide testing. The
      sensitivity of abnormal HVMA to accurately predict PCD was 90.2%. DISCUSSION AND
      CONCLUSION: This is the first report of an out-reach system to record HVMA for
      improved diagnosis of PCD in remote regions that are not within reach of PCD
      centers and experts. It provides immediate preliminary results and instantaneous
      feedback to the physician, patient and his/her family members in these areas.
      Future studies to compare this system to conventional desk top systems are
      warranted. TRIAL REGISTRATION: NCT 01070914 (registered February 6, 2010).

PMID- 25869033
TI  - Control of response reliability by parvalbumin-expressing interneurons in visual
      cortex.
AB  - The responses of visual cortical neurons to natural stimuli are both reliable and
      sparse. These properties require inhibition, yet the contribution of specific
      types of inhibitory neurons is not well understood. Here we demonstrate that
      optogenetic suppression of parvalbumin (PV)- but not somatostatin (SOM)
      expressing interneurons reduces response reliability in the primary visual cortex
      of anaesthetized and awake mice. PV suppression leads to increases in the low
      firing rates and decreases in the high firing rates of cortical neurons,
      resulting in an overall reduction of the signal-to-noise ratio (SNR). In
      contrast, SOM suppression generally increases the overall firing rate for most
      neurons, without affecting the SNR. Further analysis reveals that PV, but not
      SOM, suppression impairs neural discrimination of natural stimuli. Together,
      these results reveal a critical role for PV interneurons in the formation of
      reliable visual cortical representations of natural stimuli. 

PMID- 25869034
TI  - Roe deer sera used for TBE surveillance in Austria.
AB  - A large majority of Austrian citizens are aware of tick-borne encephalitis (TBE),
      consequently reflected by a high vaccination rate of 85%. In return, risk
      assessment and disease mapping on human cases might be hampered due to high and
      inhomogeneous vaccination rates and travel habitats of humans. The roe deer was
      used to obtain a starting point for the integral view on the actual risk of TBE
      in Austria. The roe deer exhibits several attributes which makes it suitable as
      an indicator species: the roe deer has a restricted home range and it is known to
      be a heavy tick carrier. Furthermore it sero-converts after infection with TBE,
      but no outbreak occurs. Sera from 945 roe deer were obtained from all over
      Austria and screened with IFAT for the antibodies against TBE. Twenty-two
      positive samples, 2.4%, and 17 samples at the borderline titre of 1:16 were
      identified. The majority of the positive samples, 70.6%, were located in known
      TBE areas based on human cases. Further research is needed to confirm or reject
      new endemic foci of TBE transmission. 

PMID- 25869035
TI  - Bacteria of the genus Rickettsia in ticks (Acari: Ixodidae) collected from birds
      in Costa Rica.
AB  - The aim of this study was to document the presence of Rickettsia spp. in ticks
      parasitizing wild birds in Costa Rica. Birds were trapped at seven locations in
      Costa Rica during 2004, 2009, and 2010; then visually examined for the presence
      of ticks. Ticks were identified, and part of them was tested individually for the
      presence of Rickettsia spp. by polymerase chain reaction (PCR) using primers
      targeting fragments of the rickettsial genes gltA and ompA. PCR products were DNA
      sequenced and analyzed in BLAST to determine similarities with previously
      reported rickettsial agents. A total of 1878 birds were examined, from which 163
      birds (9%) were infested with 388 ticks of the genera Amblyomma and Ixodes. The
      following Amblyomma (in decreasing order of abundance) were found in immature
      stages (larvae and nymphs): Amblyomma longirostre, Amblyomma calcaratum,
      Amblyomma coelebs, Amblyomma sabanerae, Amblyomma varium, Amblyomma maculatum,
      and Amblyomma ovale. Ixodes ticks were represented by Ixodes minor and two
      unclassified species, designated here as Ixodes sp. genotype I, and Ixodes sp.
      genotype II. Twelve of 24 tested A. longirostre ticks were found to be infected
      with 'Candidatus Rickettsia amblyommii', and 2 of 4 A. sabanerae were found to be
      infected with Rickettsia bellii. Eight of 10 larval Ixodes minor were infected
      with an endosymbiont (a novel Rickettsia sp. agent) genetically related to the
      Ixodes scapularis endosymbiont. No rickettsial DNA was found in A. calcaratum, A.
      coelebs, A. maculatum, A. ovale, A. varium, Ixodes sp. I, and Ixodes sp. II. We
      report the occurrence of I. minor in Costa Rica for the first time and a number
      of new bird host-tick associations. Moreover, 'Candidatus R. amblyommii' and R.
      bellii were found in A. longirostre and A. sabanerae, respectively, in Costa Rica
      for the first time. 

PMID- 25869037
TI  - Plagiarism, duplication and institutional publication.

PMID- 25869036
TI  - [Clinical laboratory medicine: continuous amelioration with a book of objectives
      and satisfaction survey].
AB  - We report in this publication the use of two educational tools, a questionnaire
      of satisfaction and a training book, to improve the training of students during
      their internship in clinical laboratory at the "Pole de biologie des Hopitaux
      universitaires de Strasbourg" in France. First, the ongoing training was assessed
      by the interns with a questionnaire measuring satisfaction. The analysis of this
      questionnaire identified four key points to improve: 1) define the teaching
      objectives, 2) organize the training with a schedule, 3) revise certain teaching
      methods and 4) ensure better integration of the students in the team of medical
      biologists. After this assessment, we implemented a training book to answer these
      four points. Indeed, the training book presents the objectives, the schedule of
      training, and how to validate the educational objectives. A new assessment was
      performed again using the same methodology. Results showed an improvement in
      student satisfaction from 74 to 88 %. The questionnaire of satisfaction and the
      training book are presented in this article. The aim of the assessment of
      training combined with the training book is to incite the actors of the training
      (students and teachers) to continually improve the training. The objectives of
      the Pole de Biologie are to obtain an 80 % satisfaction rate during the 6 months
      trainings and to reduce or eliminate dissatisfaction, and finally to ensure the
      validation by students of 80 to 100 % of their predetermined objectives. 

PMID- 25869038
TI  - Forensic engineering: applying materials and mechanics principles to the
      investigation of product failures.
AB  - Forensic engineering is the application of engineering principles or techniques
      to the investigation of materials, products, structures or components that fail
      or do not perform as intended. In particular, forensic engineering can involve
      providing solutions to forensic problems by the application of engineering
      science. A criminal aspect may be involved in the investigation but often the
      problems are related to negligence, breach of contract, or providing information
      needed in the redesign of a product to eliminate future failures. Forensic
      engineering may include the investigation of the physical causes of accidents or
      other sources of claims and litigation (for example, patent disputes). It
      involves the preparation of technical engineering reports, and may require giving
      testimony and providing advice to assist in the resolution of disputes affecting
      life or property.This paper reviews the principal methods available for the
      analysis of failed components and then gives examples of different component
      failure modes through selected case studies. 

PMID- 25869039
TI  - Treatments against hair loss may hinder cocaine and metabolites detection.
AB  - Recently, some of the hair samples that we routinely analyse for drugs of abuse
      did not produce valid results for cocaine and metabolites. A series of very
      intense interfering peaks with ion fragments common to cocaine (CO), and
      benzoylecgonine (BE) were found to cover up the "cocaine" region of the
      chromatogram. In one of these cases the subject declared he had used a lotion
      containing Minoxidil in order to prevent hair loss. Starting from this
      observation we found that the interfering peaks belonged to four different TMS
      derivatives of Minoxidil. Minoxidil interference was further investigated by
      applying Tricoxidil((r)), a Minoxidil solution, to the hair of CO-free volunteers
      and to a CO-positive hair strand dipped into Tricoxidil. Hair were analysed
      before and after treatment. In both cases interfering peaks were absent in the
      chromatograms of untreated hair and appeared in treated hair. In the CO-positive
      hair detection of CO, BE and internal standard was completely hindered after
      treatment with Minoxidil. Attempts to separate interfering peaks from CO and
      metabolites by modifying the temperature programme failed. None of the hair
      washing methods tested (methanol; dichloromethane; sodium dodecyl sulphate water
      solution, 1% w/v followed by methanol; phosphate buffer 0.1 M, pH 6 followed by
      methanol) succeeded in removing Minoxidil interference. However, a simple
      solution to partially overcome the problem was to dry up the derivatised extract,
      reconstitute it in methanol (in order to switch back Minoxidil derivatives to the
      native molecule), and re-inject it: owing to the higher polarity, underivatised
      Minoxidil does not interfere any more with the chromatography of CO, at the
      expense of the disappearance of BE and ecgonine methyl ester both producing TMS
      derivatives. This strategy was applied to four real cases where Minoxidil
      interference was recognised: in two of these cases CO was detected. The problem
      of Minoxidil interference on CO detection may be limited to procedures involving
      trimethylsilylation, which is probably the most commonly adopted derivatisation
      in laboratories performing hair analysis for drugs of abuse. 

PMID- 25869040
TI  - Interpretation of forensic cases based on empirical data.
AB  - Over the course of the last years the importance of hair analysis increased
      obviously. For example work place testing, driving licence cases, so-called
      health checks, and especially in criminal acts the analysis of illicit substances
      is common. With the modern multiplex analytical methods (GC/MS, GC/MS/MS, LC/MS)
      the routine analytical probe of hair is in general unproblematic. But one of the
      major problems in hair analysis is the interpretation of the results. To solve
      this difficult and challenging task statistical data as a source of information
      could be a helpful tool. Examination of more than 1,000 hair segments within the
      past 2 years using gas chromatography/tandem-mass spectrometry (GC/MS/MS) as the
      preferred method for conducting the daily routine detection of the most
      prevalently abused drugs and metabolites, such as cannabinoids, cocaine, some
      synthetic drugs from the amphetamine group, and opiates serve as the basis for
      the statistics. The quantity of analytical results and additional essential facts
      have been documented in the publication to present our sources of information and
      supplementary data to prepare forensic reports. 

PMID- 25869041
TI  - Dose-hair concentration relationship and pigmentation effects in patients on low
      dose clozapine.
AB  - Several hair components have been suggested as possible molecular sites for drug
      binding and interaction. Of these, keratin and melanin have been investigated in
      some detail in order to assess the mechanisms by which the binding occurs.
      Substances that are positively charged at physiological pH may interact by
      electrostatic forces between their cationic groups and the anionic carboxylic
      groups on the surface of the melanin polymer. Studies in human subjects with grey
      hair have shown that various drugs are detectable in both the coloured (melanin
      rich) and white (melanin free) hair shafts of these individuals. Again this
      supports the proposition that keratin and hair proteins play an important role in
      the binding of drugs in hair. However, drugs are often found in significantly
      higher concentrations in pigmented hair strands than in senile white hair
      strands. Another interesting question is if the concentration measured in hair
      reflects the dose taken. Previous reports have both verified and rejected this
      hypothesis, but most agree that many factors have impact on the incorporation
      rate, melanin being one. In this study we obtained blood and hair samples from 12
      grey haired patients treated with low-dose clozapine as an adjunct medication in
      their treatment against Parkinson disease. Each patient's hair was divided into a
      pigmented and a non-pigmented portion and those were analyzed separately.
      Clozapine and desmethylclozapine were analyzed with LC-MS-MS after extraction of
      the analytes from hair and plasma. Paired results from the analysis of pigmented
      and white hair confirmed the preference for binding to pigmented hair for both
      clozapine and its metabolite. A majority of the incorporated clozapine was found
      in the pigmented hair but, as drugs could be detected in white hair, binding to
      hair protein or association with other hair matrix account for a significant part
      of drug accumulation in hair. High correlations between dose and the measured
      concentration of analyte were found for both clozapine (r = 0.91) and
      desmethylclozapine (r = 0.88). 

PMID- 25869042
TI  - Detection of stimulant drugs of abuse in maternal and neonatal hair.
AB  - Exposure to drugs of abuse, particularly during pregnancy, is difficult to
      ascertain. Presently, there is sparse information on gestational exposure and
      fetal effects to potentially toxic drugs such as methamphetamine (MA) and
      cocaine; two of the most prevalent abused stimulants in North America. The
      Motherisk laboratory at the Hospital for Sick Children routinely carries out
      analysis of MA and cocaine in adult and infant hair. All mother-child pairs in
      whom at least one had cocaine and/or benzoylecgonine (BE), or MA detected in hair
      were identified from the Motherisk database. Eleven mother-infant pairs with
      positive hair for MA were identified. One infant (9%) had a negative MA result
      with a positive maternal result. There was not any positive infant hair with
      negative maternal hair for MA. MA concentrations in mothers and infants
      correlated positively and were not significantly different. Median cocaine
      concentrations were tenfold higher in hair of the mothers compared to the
      infants. Thirty-nine (40%) infants had negative cocaine and BE with positive
      maternal results. Mothers whose infants were cocaine positive had median cocaine
      significantly higher than those whose infants were negative. Infants' cocaine in
      hair was positively correlated with maternal cocaine and BE. Infants' BE
      correlated with maternal cocaine and BE concentrations. Fetal hair grows during
      the last trimester of pregnancy; therefore a positive neonatal hair result
      indicates maternal use after pregnancy is known, a strong indicator of maternal
      addiction. To our knowledge, this is the first report on fetal exposure to MA
      during pregnancy showing transplacental transfer of the drug, with accumulation
      in fetal hair. Transplacental exposure to cocaine of babies of addicted mothers
      is highly variable. Further research is needed to understand the mechanisms
      leading to placental defense against cocaine. 

PMID- 25869043
TI  - Individual variations of amitriptyline biotransformation examined in scalp hair
      samples.
AB  - The identification of amitriptyline, nortriptyline and its hydroxy-metabolites
      including a subsequent measurement of concentration profiles in hair samples was
      carried out to evaluate the administration history of amitriptyline. Analyses
      were carried out using liquid chromatography-tandem mass spectrometry, which
      permits simultaneous identification of all relevant substances in hair at low
      target concentrations (limit of detection better than 0.5 pg/mg). Standard hair
      sample preparation was applied for the estimation of average substance
      concentration in a hair bundle, while segmentation of individual hairs was
      utilised to examine accurate concentration profiles. Replication of analyses
      demonstrated a good reproducibility of individual hair concentration profiles,
      which proved to coincide for all relevant compounds. Significant variations of
      metabolite ratios (e.g. nortriptyline to amitriptyline and E10- to Z10
      hydroxynortriptyline) between individuals suggest a correlation between hair
      concentration and metabolic phenotype. Different concentration ratios of certain
      metabolites in hair are highly correlated, indicating a systematic association
      between demethylation and stereo-specificity of hydroxylation. The trans isomers
      of hydroxy-metabolites become significantly more prevalent with increasing degree
      of demethylation of amitriptyline or hydroxylation of amitriptyline. 

PMID- 25869044
TI  - An unusual case of crossbow homicide.
AB  - The authors report the case of a man found unresponsive in a wooded area with
      injuries on the face, eyes, shoulders and back, probably produced by caustic
      agents. A penetrating wound was noted in the left occipital region. Four days
      after admission to an Intensive Care Unit he died. No weapon was found at the
      crime scene. Autopsy revealed an occipital bone defect in the wound area, and
      cerebral haemorrhage in the left hemisphere in the absence of an exit wound.
      Immunohistochemical staining of brain samples for beta-APP were critical
      establishing the extent of the injury. The peculiarity of the wound and the lack
      of circumstantial evidence made it necessary to conduct a careful investigation
      to identify the weapon. Firing tests performed on experimental cranial models
      established the use of a crossbow weapon as a cause of the observed wound. 

PMID- 25869045
TI  - Forensic issues in cases of fatal hemorrhage from arteriovenous dialysis access
      sites.
AB  - Angioaccess sites to enable repetitive vascular punctures for hemodialysis
      include temporary or permanent indwelling catheters, port access devices,
      autogenous vessels in native arteriovenous fistulas, or non-autogenous material
      in prosthetic arteriovenous grafts. While complications such as thrombosis and
      infection are well recognized, lethal hemorrhage is much less commonly
      encountered. In this paper, selected cases are reported to demonstrate the range
      of situations that may be encountered at autopsy, including hemorrhage from a
      catheter in a case of suicide, and hemorrhage from an arteriovenous fistula and
      an arteriovenous graft. Predisposing factors to hemorrhage include coagulation
      abnormalities due to anticoagulant therapy or to underlying renal failure,
      stenosis or obstruction that has resulted in increased intraluminal pressure,
      local sepsis, repeated trauma from venesection and hypertension. An approach to
      such cases should include careful evaluation of the medical history and death
      scene, with dissection at autopsy of catheters, grafts and fistulas to
      demonstrate the condition of anastomosis sites, and the presence or absence of
      ruptures, perforations, stenoses, and/or thromboses. Histologic sampling of
      autologous fistula walls and surrounding soft tissues may reveal evidence of
      sepsis. 

PMID- 25869046
TI  - DNA reviews: hair.
AB  - Human and nonhuman hairs are often recovered during forensic investigation. As
      with all other biological samples that may be collected, via DNA analysis, hairs
      have the potential to provide the investigating authority with valuable
      intelligence pertaining to the identity of offenders, victims and even pets. DNA
      analysis of hairs is not however a straightforward process. The biochemical make
      up of hairs provide the DNA analyst with a unique set of challenges that must be
      overcome before any useful information can be gleaned from the evidence. This
      short review provides an overview of the location and condition of DNA within
      hair samples, and discusses the analytical methods that are employed to maximise
      the information that can be obtained from this sample type. 

PMID- 25869047
TI  - Mobile computed tomography for mass fatality investigations.
AB  - The use of computed tomography (CT) has received growing interest within the
      forensic world. To date, most publications have been related to the use of
      clinical or institutional sited scanners with few publications reporting on the
      actual, as opposed to the theoretical, use of mobile CT scanners in forensic
      practice. This review paper considers the use of mobile CT scanning for forensic
      investigations. It reviews the literature and presents the experience gained from
      a 6-month trial undertaken by the Forensic Pathology Unit, at the University of
      Leicester, UK of the use of CT for mass fatality investigation. Protocols for the
      use of mobile CT are discussed to assist other centres contemplating the use of
      mobile CT for mass fatality investigations. 

PMID- 25869049
TI  - Society of hair testing annual meeting abstracts, vadstena, sweden, may 28-30,
      2006.

PMID- 25869048
TI  - Ba'alat.

PMID- 25869050
TI  - Abstracts : BAFM Winter Meeting 2006, Leicester, UK.

PMID- 25869052
TI  - GAS6 intron 8 c.834 + 7G > A gene polymorphism in diabetic nephropathy.
AB  - BACKGROUND - AIM: In animal experiments, growth arrest-specific 6 (Gas6) protein
      plays a key role in the development of mesangial cell and glomerular hypertrophy
      in the early phase of diabetic nephropathy, and diabetic nephropathy is prevented
      by warfarin-induced inhibition of GAS6 protein. It was shown that GAS6 intron 8
      c.834 + 7G > A polymorphism is protective against type 2 diabetes mellitus, and
      AA genotype is associated with higher blood levels of GAS6 protein. Our aim is to
      investigate whether this polymorphism is a risk factor for diabetic nephropathy
      in type 2 diabetes mellitus. METHOD: Eighty-seven patients with diabetic
      nephropathy were compared with 66 non-diabetic controls in terms of GAS6 intron 8
      c.834 + 7G > A polymorphism. Patients with history of stroke, ischemic heart
      disease were excluded. Each patient was examined by the ophthalmologist to
      determine diabetic retinopathy. RESULTS: Frequency of GG, GA and AA genotypes are
      similar in diabetic nephropathy and control groups according to GAS6 intron 8
      c.834 + 7G > A polymorphism (p =  .837). Rate of diabetic retinopathy was 54.02%.
      In the subgroup analysis, GA genotype was significantly more frequent than GG
      genotype in patients with diabetic retinopathy when compared to without diabetic
      retinopathy (p =  .010). CONCLUSION: In our study, GAS6 intron 8 c.834 + 7G > A
      polymorphism was not associated with diabetic nephropathy in type 2 diabetes
      mellitus. However, heterozygous state of this polymorphism may be a risk factor
      for diabetic retinopathy in patients with diabetic nephropathy.

PMID- 25869053
TI  - C4d deposition is associated with immune cells infiltrating in kidney allograft
      glomerulitis and peritubular capillaritis.
AB  - OBJECTIVE: The aim of our study was to determine the amount and composition of
      immune cells within glomeruli and PTCs and its relationship with C4d deposition.
      MATERIALS AND METHODS: Immunohistochemistry staining for C4d, CD3, CD68, granzyme
      B and Foxp3 was used for phenotyping and enumerating immune cells within
      intracapillaries. RESULTS: C4d staining was present in 26 biopsy specimens
      (C4d(+)) and negative in 25 specimens (C4d(-)). The total number of infiltrating
      cells in glomerulus and PTC in C4d(+) was significantly higher than in C4d(-).
      Although the C4d(+) showed a significantly higher mean number of macrophages per
      glomerulus and PTC than in C4d(-) group, the C4d(-) showed a higher mean number
      of T cells per glomerulus and PTC than in C4d(+). Comparing cell counts in
      diffuse C4d(+) and focal C4d(+) groups, a significant difference of absolute
      numbers of intracapillary cells could be observed in glomeruli and PTCs. The mean
      number of macrophages per glomerulus and PTC in diffuse C4d(+) was greater than
      that of the focal C4d(+), while mean T cells per glomerulus and PTC were less in
      cases of diffuse C4d(+) than in focal C4d(+). The differences, however, did not
      achieve statistical significance. Not only glomerular T cells but also PTCs are
      granzyme B positive T cells totally. CONCLUSION: The total number of infiltrating
      cells in glomeruli and PTC has association with PTC C4d deposition; the
      infiltrating cells were predominantly macrophages in C4d(+), especially in
      diffuse C4d(+), whereas the infiltrating cells were predominantly T cells in C4d(
      ). Glomerular and PTC T cells were cytotoxic phenotype completely.

PMID- 25869054
TI  - Urine neutrophil gelatinase-associated lipocalin levels predict acute kidney
      injury in acute decompensated heart failure patients.
AB  - BACKGROUND: Acute heart failure (HF) syndromes are frequently complicated with
      cardiorenal syndromes. The aim of this study was to evaluate the performance of
      admission neutrophil gelatinase associated lipocalin (NGAL) levels to predict
      diuretic dose requirement and to predict the occurrence of acute kidney injury
      (AKI) in patients presenting with acute decompensated HF. METHODS: Patients
      admitted with HF symptoms between December 2010 and October 2011 were
      prospectively enrolled. Samples were obtained for NGAL and brain natriuretic
      peptide. Patients were followed up until discharge or for three days, whichever
      happened first. They were grouped either to have AKI according to "Acute Kidney
      Injury Network" criteria or not ("no-AKI"). RESULTS: One hundred patients were
      enrolled. Urine NGAL levels were higher in AKI group (median 31.3 vs. 16.2 ng/mL)
      (p < 0.001). Oral furosemide using rates on admission was 60.5% in AKI group,
      31.6% in no-AKI group. More AKI developed in patients using less furosemide
      orally on admission (p = 0.023). Although the mean furosemide doses were similar
      on the first day (80 mg), diuretic dose increment was less on the following days
      in AKI group. Urine NGAL levels with 12 ng/mL cut-off value had sensitivity of
      79% and specificity of 67% for predicting AKI. Multiple logistic regression
      analysis yielded an odds ratio of 10.9 for NGAL levels to predict AKI.
      CONCLUSION: Urine NGAL level in decompensated HF patients was not a significant
      predictor of diuretic dose requirement, but was a good marker for predicting AKI
      at 12 ng/mL cut-off value.

PMID- 25869055
TI  - Association of kidney and cysts dimensions with anthropometric and biochemical
      parameters in patients with ADPKD.
AB  - The aim of the study was to evaluate an association between kidney and cyst
      dimensions and anthropometric, clinical and biochemical parameters of autosomal
      dominant polycystic kidney disease (ADPKD) patients. Forty-nine adults, ADPKD
      diagnosed patients aged 36 +/- 11 years, and 50 healthy controls were included in
      the study. Oral glucose tolerance test (OGTT with 75 g of glucose) was performed
      and venous blood was collected to measure biochemical parameters and various ion
      concentrations. Ultrasound abdominal examinations were performed with special
      emphasis on kidney and cysts parameters. In the ADPKD group, mean kidney length
      correlated positively with age, systolic blood pressure (SBP), diastolic blood
      pressure (DBP), fasting glucose and glucose and C-peptide concentrations after
      120 min of glucose intake and negatively with Mg(2+) concentration and glomerular
      filtration rate (eGFR). Multivariate analyses adjusted for age and gender showed
      that higher mean kidney length and maximal cyst diameter were significant
      predictors of higher SBP (p = 0.034 and 0.046, respectively) and DBP (p = 0.024
      and 0.034, respectively), higher maximal cyst diameter was a significant
      predictor of higher OGTT 2-h C-peptide concentration (p = 0.033), higher mean
      cyst diameter was a significant predictor of lower eGFR (p = 0.039) and higher
      mean kidney length was a significant predictor of lower serum magnesium
      concentration (p = 0.043). In the ADPKD patients with normal GFR, mean kidney
      length and mean cyst diameter measured by ultrasonography are associated
      negatively with GFR and positively with blood pressure. Higher mean kidney length
      and cyst diameter might be indicators of disorders of glucose and magnesium
      metabolism which precede renal failure in patients with ADPKD.

PMID- 25869056
TI  - Andrographolide suppresses melanin synthesis through Akt/GSK3beta/beta-catenin
      signal pathway.
AB  - BACKGROUND: Tyrosinase (TYR) is the key enzyme controlling the production of
      melanin. Very few papers have reported that andrographolide can inhibit melanin
      content. OBJECTIVE: To investigate the effects of andrographolide on melanin
      synthesis. METHODS: Cell viability, melanin content, TYR activity,
      transcriptional and protein expression levels of TYR family and other kinds of
      proteins involved in melanogenesis were measured after the treatments of
      andrographolide. RESULTS: It was found that andrographolide decreased melanin
      content, TYR activity and transcriptional and protein expression of TYR family
      and microphthalmia-associated transcription factor (MITF) in B16F10 melanoma
      cells. Data showed andrographolide also decreased melanin content and TYR content
      in ultraviolet B (UVB) irradiation induced brown guinea pigs. Moreover, we found
      that melanin content and TYR activity were effectively inhibited in Human
      Epidermis Melanocyte (HEM) treated with andrographolide at the medium
      concentrations without apparent effect on cell viability. Results in experiments
      treated with MG-132 or cycloheximide (CHX) showed that andrographolide lowered
      the content of beta-catenin in cell nucleus resulting from accelerating the
      degradation of beta-catenin. Phosphorylation of glycogen synthase kinase 3beta
      (GSK3beta) and Akt decreased simultaneously. 6-Bromoindirubin-3'-oxime (BIO,
      inhibitor of GSK3beta) and insulin-like growth factors-1 (IGF-1, activator of
      Akt) could reverse the decline of beta-catenin in B16F10 cells induced by
      andrographolide. CONCLUSION: These results demonstrate that andrographolide can
      effectively suppress melanin content and TYR activity in B16F10 cells, HEM cells
      and UVB-induced brown guinea pig skin by decreasing phosphorylation of GSK3beta
      dependent on Akt, promoting the degradation of beta-catenin, inhibiting beta
      catenin into the nucleus and decreasing the expression of MITF and TYR family.
      Data indicate that andrographolide may be a potential whiting agent which can
      have great market in cosmetics and in clinical such as curing hyperpigmentation
      disorders.

PMID- 25869057
TI  - Gene expression and physiological responses to salinity and water stress of
      contrasting durum wheat genotypes.
AB  - Elucidating the relationships between gene expression and the physiological
      mechanisms remains a bottleneck in breeding for resistance to salinity and
      drought. This study related the expression of key target genes with the
      physiological performance of durum wheat under different combinations of salinity
      and irrigation. The candidate genes assayed included two encoding for the DREB
      (dehydration responsive element binding) transcription factors TaDREB1A and
      TaDREB2B, another two for the cytosolic and plastidic glutamine synthetase (TaGS1
      and TaGS2), and one for the specific Na(+) /H(+) vacuolar antiporter (TaNHX1).
      Expression of these genes was related to growth and different trait indicators of
      nitrogen metabolism (nitrogen content, stable nitrogen isotope composition, and
      glutamine synthetase and nitrate reductase activities), photosynthetic carbon
      metabolism (stable carbon isotope composition and different gas exchange traits)
      and ion accumulation. Significant interaction between genotype and growing
      conditions occurred for growth, nitrogen content, and the expression of most
      genes. In general terms, higher expression of TaGS1, TaGS2, TaDREB2B, and to a
      lesser extent of TaNHX1 were associated with a better genotypic performance in
      growth, nitrogen, and carbon photosynthetic metabolism under salinity and water
      stress. However, TaDREB1A was increased in expression under stress compared with
      control conditions, with tolerant genotypes exhibiting lower expression than
      susceptible ones. 

PMID- 25869058
TI  - [Recommendations for management of acute pharyngitis in adults].
AB  - Acute pharyngitis in adults is one of the most common infectious diseases seen in
      general practitioners' consultations. Viral aetiology is the most common. Among
      bacterial causes, the main agent is Streptococcus pyogenes or group A beta
      haemolytic streptococcus (GABHS), which causes 5%-30% of the episodes. In the
      diagnostic process, clinical assessment scales can help clinicians to better
      predict suspected bacterial aetiology by selecting patients who should undergo a
      rapid antigen detection test. If these techniques are not performed, an
      overdiagnosis of streptococcal pharyngitis often occurs, resulting in unnecessary
      prescriptions of antibiotics, most of which are broad spectrum. Consequently,
      management algorithms that include the use of predictive clinical rules and rapid
      tests have been set up. The aim of the treatment is speeding up symptom
      resolution, reducing the contagious time span and preventing local suppurative
      and non-suppurative complications. Penicillin and amoxicillin are the antibiotics
      of choice for the treatment of pharyngitis. The association of amoxicillin and
      clavulanate is not indicated as the initial treatment of acute infection. Neither
      are macrolides indicated as first-line therapy; they should be reserved for
      patients allergic to penicillin. The appropriate diagnosis of bacterial
      pharyngitis and proper use of antibiotics based on the scientific evidence
      available are crucial. Using management algorithms can be helpful in identifying
      and screening the cases that do not require antibiotic therapy.

PMID- 25869059
TI  - Inconsistent treatment estimates from mis-specified logistic regression analyses
      of randomized trials.
AB  - When the difference between treatments in a clinical trial is estimated by a
      difference in means, then it is well known that randomization ensures unbiassed
      estimation, even if no account is taken of important baseline covariates.
      However, when the treatment effect is assessed by other summaries, for example by
      an odds ratio if the outcome is binary, then bias can arise if some covariates
      are omitted, regardless of the use of randomization for treatment allocation or
      the size of the trial. We present accurate closed-form approximations for this
      asymptotic bias when important normally distributed covariates are omitted from a
      logistic regression. We compare this approximation with ones in the literature
      and derive more convenient forms for some of these existing results. The
      expressions give insight into the form of the bias, which simulations show is
      usable for distributions other than the normal. The key result applies even when
      there are additional binary covariates in the model.

PMID- 25869060
TI  - Bilateral optic neuropathy following bite from brown recluse spider (Loxosceles
      reclusa).
AB  - A 63-year-old female with history of a resected frontal lobe meningioma presented
      with bilaterally decreased vision after a bite from a brown recluse spider. The
      exam was significant for a left relative afferent pupillary defect, bilateral
      optic nerve pallor, decreased foveal sensitivity in the left eye and new
      bilateral visual field defects, despite stability of her meningioma. The findings
      remained stable at 1-year follow-up. To our knowledge, this is the first reported
      case of optic neuropathy secondary to a brown recluse spider bite. Visual field
      tests performed prior to the bite allowed us to compare and localize changes
      related to the bite. 

PMID- 25869061
TI  - Network Meta-analysis: Users' Guide for Surgeons: Part I - Credibility.
AB  - Conventional meta-analyses quantify the relative effectiveness of two
      interventions based on direct (that is, head-to-head) evidence typically derived
      from randomized controlled trials (RCTs). For many medical conditions, however,
      multiple treatment options exist and not all have been compared directly. This
      issue limits the utility of traditional synthetic techniques such as meta
      analyses, since these approaches can only pool and compare evidence across
      interventions that have been compared directly by source studies. Network meta
      analyses (NMA) use direct and indirect comparisons to quantify the relative
      effectiveness of three or more treatment options. Interpreting the methodologic
      quality and results of NMAs may be challenging, as they use complex methods that
      may be unfamiliar to surgeons; yet for these surgeons to use these studies in
      their practices, they need to be able to determine whether they can trust the
      results of NMAs. The first judgment of trust requires an assessment of the
      credibility of the NMA methodology; the second judgment of trust requires a
      determination of certainty in effect sizes and directions. In this Users' Guide
      for Surgeons, Part I, we show the application of evaluation criteria for
      determining the credibility of a NMA through an example pertinent to clinical
      orthopaedics. In the subsequent article (Part II), we help readers evaluate the
      level of certainty NMAs can provide in terms of treatment effect sizes and
      directions. 

PMID- 25869062
TI  - Network Meta-analysis: Users' Guide for Surgeons: Part II - Certainty.
AB  - In the previous article (Network Meta-analysis: Users' Guide for Surgeons-Part I,
      Credibility), we presented an approach to evaluating the credibility or
      methodologic rigor of network meta-analyses (NMA), an innovative approach to
      simultaneously addressing the relative effectiveness of three or more treatment
      options for a given medical condition or disease state. In the second part of the
      Users' Guide for Surgeons, we discuss and demonstrate the application of criteria
      for determining the certainty in effect sizes and directions associated with a
      given treatment option through an example pertinent to clinical orthopaedics. 

PMID- 25869063
TI  - From Bench to Bedside: Alpha-defensing--The Biggest Thing in Joint Replacement
      Infections Since Prophylactic Antibiotics?

PMID- 25869064
TI  - From Bench to Bedside: It's Cold in There-Isn't It Time We Gave Our Implants a
      Coat?

PMID- 25869065
TI  - Light-mediated DNA Repair Prevents UVB-induced Cell Cycle Arrest in Embryos of
      the Crustacean Macrobrachium olfersi.
AB  - High levels of ultraviolet-B (UVB) radiation can negatively affect aquatic
      animals. Macrobrachium olfersi is a prawn that lives in clear freshwaters and
      during the breeding season, females carry eggs in an external brood pouch.
      Therefore, we hypothesize that eggs are also exposed to environmental UVB
      radiation. The aim of this study was to investigate whether UVB radiation induces
      DNA damage and compromises cell cycle in embryos of M. olfersi. In laboratory,
      UVB irradiance (310 mW. cm(-2) ) that embryos receive in the natural environment
      was simulated. After irradiation, embryos were kept under different light
      conditions in order to recognize the presence of cell repair. UVB radiation
      induces DNA damage, specifically thymine dimers. After 48 h of UVB exposure, a
      significant decrease in the level of these dimers was observed in embryos kept
      under visible light while it remained constant in the dark. Moreover, under
      visible light and darkness, a decrease in proliferation was observed after 48 h
      of irradiation. An increase in PCNA expression and decrease in p53 expression
      were observed after, respectively, 1 and 48 h of exposure. Our results showed
      that UVB radiation disturbs the cell cycle and induces DNA damage in M. olfersi
      embryos. However, under visible light these embryos showed successful DNA repair.

PMID- 25869066
TI  - Girdin/GIV regulates transendothelial permeability by controlling VE-cadherin
      trafficking through the small GTPase, R-Ras.
AB  - Vascular permeability is regulated by intercellular junction organization of
      endothelial cells, the dysfunction of which is implicated in numerous
      pathological conditions. Molecular mechanisms of how endothelial cells regulate
      intercellular junction in response to extracellular signals, however, have so far
      remained elusive. This study identified that Girdin (also termed GIV), an Akt
      substrate functioning in post natal angiogenesis, was expressed in a mature
      endothelial monolayer, where it regulated VE-cadherin trafficking to maintain
      vascular integrity. Girdin depletion abrogated VEGF-induced VE-cadherin
      endocytosis and the disassembly of adherens junctions in a monolayer of
      endothelial cells, thus leading to a significant decrease in the permeability. We
      also showed that activated R-Ras, a member of the Ras family GTPase, known to be
      a master regulator of transendothelial permeability, interacts with Girdin, and
      facilitates the complex formation between Girdin and VE-cadherin in endothelial
      cells. However, the increased permeability mediated by the loss of R-Ras was
      rescued by Girdin depletion, thus suggesting that the interaction of Girdin with
      R-Ras functions in VE-cadherin trafficking pathways distinct from endocytosis.
      The recycling of VE-cadherin was promoted by the exogenous expression of the
      active mutant of R-Ras, which was attenuated in the Girdin-depleted endothelial
      cells. These results show that Girdin regulates transendothelial permeability in
      synergy with R-Ras and VE-cadherin in an endothelial monolayer. 

PMID- 25869067
TI  - Dietary vitamin D3 improves postprandial hyperglycemia in aged mice.
AB  - Type 2 Diabetes is closely associated with our daily diets and has become a
      global health problem with an increasing number of patients. Recent observational
      and randomized studies on vitamin D3 suggested that higher plasma 25
      hydroxyvitamin D3 [25(OH)D3] concentrations and more vitamin D3 intake are
      associated with lower risk of type 2 diabetes, which is characterized by
      postprandial hyperglycemia due to inappropriate glucose stimulated insulin
      secretion (GSIS) and its age-dependent increase of onset. However, rapid action
      of dietary vitamin D3 on the postprandial glucose profile has not been analyzed.
      When vitamin D3 is orally ingested in mice aged 12-14 weeks during an oral
      glucose tolerance test (OGTT), the serum glucose profile was not changed. In
      contrast, when OGTT was performed with old mice aged 30-34 weeks, the glucose
      profile was dramatically improved with increased insulin secretion, suggesting
      that orally ingested vitamin D3 potentiated GSIS in aged mice. Interestingly,
      there was also a significant increase in plasma GLP-1 in these aged mice. Our
      results suggest that orally ingested dietary vitamin D3 in aged mice improves
      glucose metabolism as a GLP-1 enhancer. 

PMID- 25869068
TI  - Inactivation of Itf2 promotes intestinal tumorigenesis in Apc(Min/+) mice.
AB  - Deregulation of Wnt/beta-catenin signaling following inactivation of the
      adenomatous polyposis coli (APC) tumor suppressor gene is frequently found in
      colorectal cancer. We have previously shown that levels of ITF-2B, encoded by the
      beta-catenin target gene ITF2 that is located on the tumor suppressor gene locus
      18q21, are increased in colonic adenomas with deregulated beta-catenin activity.
      However, during tumor progression ITF-2B levels are reduced, suggesting that ITF
      2B interferes with tumor development. To investigate the role of ITF2 in
      intestinal tumorigenesis, we specifically inactivated Itf2 in the intestinal
      epithelium of Apc(Min/+) mice. We found that genetic disruption of Itf2 on the
      Apc(Min/+) background results in earlier death and a significant increase in
      tumor number and size in the small intestine. Based on these data Itf2 acts as a
      tumor suppressor gene of the intestinal tract that inhibits tumor initiation and
      growth. 

PMID- 25869069
TI  - Arsenic trioxide synergistically potentiates the cytotoxic effect of fludarabine
      in chronic lymphocytic leukemia cells by further inactivating the Akt and ERK
      signaling pathways.
AB  - CLL remains an incurable disease, making it crucial to continue searching for new
      therapies efficient in all CLL cases. We have studied the effect of combining
      arsenic trioxide (ATO) with fludarabine, a frontline drug in CLL. We have found a
      synergistic interaction between 1 MUM ATO and 5 MUM fludarabine that
      significantly enhanced the cytotoxic effect of the individual drugs. Importantly,
      ATO sensitized fludarabine-resistant cells to the action of this drug. The
      mechanism behind this effect included the downregulation of phospho-Akt, phospho
      ERK, and the Mcl-1/Bim and Bcl-2/Bax ratios. The combination of ATO and
      fludarabine partially overcame the survival effect induced by co-culturing CLL
      cells with stromal cells. Therefore, low concentrations of ATO combined with
      fludarabine may be an efficient therapeutic strategy in CLL patients. 

PMID- 25869070
TI  - High salt-diet reduces SLC14A1 gene expression in the choroid plexus of Dahl salt
      sensitive rats.
AB  - Elevated Na(+) concentration ([Na(+)]) in the cerebrospinal fluid (CSF)
      contributes to the development of salt-sensitive hypertension. CSF is formed by
      the choroid plexus (CP) in cerebral ventricles, and [Na(+)] in CSF is controlled
      by transporters in CP. Here, we examined the effect of high salt diet on the
      expression of urea transporters (UTs) in the CP of Dahl S vs Dahl R rats using
      real time PCR. High salt intake (8%, for 2 weeks) did not alter the mRNA levels
      of UT-A (encoded by SLC14A2 gene) in the CP of either Dahl S or Dahl R rats. In
      contrast, the mRNA levels of UT-B (encoded by SLC14A1 gene) were significantly
      reduced in the CP of Dahl S rats on high salt diet as compared with Dahl R rats
      or Dahl S rats on normal salt diet. Reduced UT-B expression was associated with
      increased [Na(+)] in the CSF and elevated mean arterial pressure (MAP) in Dahl S
      rats treated with high salt diet, as measured by radiotelemetry. High salt diet
      induced reduction in UT-B protein expression in the CP of Dahl S rats was
      confirmed by Western blot. Immunohistochemistry using UT-B specific antibodies
      demonstrated that UT-B protein was expressed on the epithelial cells in the CP.
      These data indicate that high salt diet induces elevations in CSF [Na(+)] and in
      MAP, both of which are associated with reduced UT-B expression in the CP of Dahl
      S rats, as compared with Dahl R rats. The results suggest that altered UT-B
      expression in the CP may contribute to an imbalance of water and electrolytes in
      the CSF of Dahl S rats on high salt diet, thereby leading to alterations in MAP. 

PMID- 25869071
TI  - Myostatin regulates miR-431 expression via the Ras-Mek-Erk signaling pathway.
AB  - MicroRNAs (miRNAs) play critical regulatory roles in controlling myogenic
      development both in vitro and in vivo; however, the molecular mechanisms
      underlying transcriptional regulation of miRNA genes in skeletal muscle cells are
      largely unknown. Here, using a microarray hybridization approach, we identified
      myostatin-regulated miRNA genes in skeletal muscle tissues by systematically
      searching miRNAs that are differentially expressed between wild-type and
      myostatin-null mice during development. We found that 116 miRNA genes were
      differentially expressed in muscles between these mice across different
      developmental stages. We further characterized myostatin-regulated miR-431 was
      upregulated in skeletal muscle tissues of myostatin-null mice. In functional
      studies, we found that overexpression of miR-431 in C2C12 myoblast cells
      attenuated myostatin-induced suppression of myogenic differentiation. Mechanistic
      studies further demonstrated that myostatin acted through the Ras-Mek-Erk
      signaling pathway to transcriptionally regulate miR-431 expression C2C12 cells.
      Our findings provide new insight into the mechanisms underlying transcriptional
      regulation of miRNA genes by myostatin during skeletal muscle development. 

PMID- 25869072
TI  - Transforming growth factor-alpha induces human ovarian cancer cell invasion by
      down-regulating E-cadherin in a Snail-independent manner.
AB  - Transforming growth factor-alpha (TGF-alpha), like epidermal growth factor (EGF)
      and amphiregulin (AREG) binds exclusively to EGF receptor (EGFR). We have
      previously demonstrated that EGF, AREG and TGF-alpha down-regulate E-cadherin and
      induce ovarian cancer cell invasion, though whether these ligands use the same
      molecular mediators remains unknown. We now show that, like EGF, TGF-alpha- and
      AREG-induced E-cadherin down-regulation involves both EGFR and HER2. However, in
      contrast to EGF and AREG, the transcription factor Snail is not required for TGF
      alpha-induced E-cadherin down-regulation. This study shows that TGF-alpha uses
      common and divergent molecular mediators to regulate E-cadherin expression and
      cell invasion. 

PMID- 25869073
TI  - Suppression of liver receptor homolog-1 by microRNA-451 represses the
      proliferation of osteosarcoma cells.
AB  - Liver receptor homolog-1 (LRH-1) plays an important role in the onset and
      progression of many cancer types. However, the role of LRH-1 in osteosarcoma has
      not been well investigated. In this study, the critical role of LRH-1 in
      osteosarcoma cells was described. Quantitative polymerase chain reaction and
      Western blot analysis results revealed that LRH-1 was highly overexpressed in
      osteosarcoma cells. LRH-1 was knocked down by small interfering RNA (siRNA), and
      this phenomenon significantly inhibited osteosarcoma cell proliferation.
      Bioinformatics analysis results showed that LRH-1 contained putative binding
      sites of microRNA-451 (miR-451); this result was further validated through a dual
      luciferase activity reporter assay. miR-451 was overexpressed in osteosarcoma
      cells through transfection of miR-451 mimics; miR-451 overexpression then
      significantly inhibited LRH-1 expression and cell proliferation. The loss of LRH
      1 by siRNA or miR-451 mimics significantly impaired Wnt/beta-catenin activity,
      leading to G0/G1 cell cycle arrest. Results showed that LRH-1 is implicated in
      osteosarcoma. Therefore, miR-451-induced suppression of LRH-1 can be a novel
      therapy to treat osteosarcoma. 

PMID- 25869074
TI  - [CD15 focus score for diagnostics of periprosthetic joint infections :
      Neutrophilic granulocytes quantification mode and the development of morphometric
      software (CD15 quantifier)].
AB  - BACKGROUND: The aim of this project was to devise a quantification method for
      neutrophils within a single focal point through the development of a CD15 focus
      score which enables bacterial infections in synovial-like interface membranes
      (SLIM) to be diagnosed. METHODS: In this study a histopathological classification
      of 91 SLIM removed during revision surgery from the hips (n = 59) and knees (n =
      32) was performed. Neutrophils were identified immunohistochemically by means of
      a CD15-specific monoclonal antibody. The quantitative evaluation of CD15-positive
      neutrophils (CD15Ne) used the principle of maximum focal infiltration (focus)
      together with an assessment of a single focal point (0.3 mm(2)). This
      immunohistochemical approach made it possible to develop the CD15 quantifier
      software, which automatically quantifies CD15Ne. RESULTS: The SLIM cases with
      positive microbiological findings (n = 47) had significantly (p < 0.001, Mann
      Whitney U-test) more CD15Ne/focal point than cases with negative microbiological
      findings (n = 44). A count of 50 CD15Ne/focal point was identified as the optimum
      threshold when diagnosing periprosthetic joint infections (PJI) using the CD15
      focus score. If the microbiological findings are used as a gold standard, the
      diagnostic sensitivity is 0.83, and the specificity is 0.864 with a positive
      predictive value (PPV) of 0.87, a negative predictive value (NPV) of 0.83, an
      accuracy of 0.846 and an area under the curve (AUC) of 0.878. The evaluation of
      findings for the preparations using the CD15 quantifier software (n = 31)
      deviated by an average of 12 cells from the histopathological evaluation findings
      (CD15 focus score). Above a cell count of 62, the CD15-quantifier needs on
      average 32 s less than the pathologist. CONCLUSION: The immunohistochemical CD15
      focus score has a high diagnostic value and allowed the development of the CD15
      quantifier software. This provides an automated procedure, which shortens the
      mentally tiring and time-consuming process of microscopic cell counting and thus
      makes a contribution towards the standardization of tools for diagnosing PJI.

PMID- 25869075
TI  - Rates and predictors of genital warts burden in the Czech population.
AB  - OBJECTIVE: To describe the burden and the predictors of genital warts (GWs) in
      Czech men and women. METHODS: A population-based cross-sectional study was
      conducted of 32 974 randomly selected health clinic attendees from all 14 regions
      of the Czech Republic. Information on GWs and lifestyle behaviour was collected
      using a questionnaire. RESULTS: Results revealed a 5.8% prevalence rate of self
      reported GWs in the Czech population aged 16-55 years. There was an increase in
      the incidence of GWs in the years 2010-2013 when compared to lifetime incidence
      rates, from 205.4 (95% confidence interval (CI) 191.0-219.7) to 441.8 (95% CI
      393.1-490.6) per 100 000 person-years. No significant differences were observed
      between genders. The strongest risk factors found for GWs were an infected sexual
      partner (adjusted odds ratio (OR) 114.3, 95% CI 78.9-165.4) and a high number of
      lifetime sexual partners (adjusted OR 3.36, 95% CI 2.72-4.17 for >14 partners vs.
      one partner). A novel finding was that 22.7% (95% CI 20.9-24.6%) of participants
      claimed that the pathology had disappeared spontaneously without medical
      assistance. CONCLUSIONS: The results provide baseline information for the
      development and monitoring of prevention strategies against GWs in the Czech
      Republic.

PMID- 25869076
TI  - A case of infectious endocarditis due to BCG.
AB  - The occurrence of bacillus Calmette-Guerin (BCG) disease following instillation
      for bladder cancer is commonly documented. The intravesical administration of BCG
      is generally safe, but may present severe complications. A fatal case of native
      aortic valve infectious endocarditis with septicemia due to BCG in a patient
      treated with intravesical instillation is reported herein. 

PMID- 25869077
TI  - Variations in erythropoiesis-stimulating agent administration in transfusion
      dependent myelodysplastic syndromes impact response.
AB  - INTRODUCTION: Erythropoiesis-stimulating agents (ESAs) reduce red blood cell
      (RBC) transfusions in approximately 40% of patients with myelodysplastic syndrome
      (MDS) in clinical trials. We studied the association of timing of ESA initiation,
      agent (epoetin alfa, darbepoetin) and number of weeks of ESA use with response in
      MDS patients in routine practice. METHODS: Patients diagnosed with MDS from 2001
      to 2005 were identified in the Surveillance Epidemiology and End Results-Medicare
      linked database. The study cohort consisted of patients with new-onset
      transfusion dependence (TD). All patients received an ESA at least once during
      the study period, which began the week that criteria for TD were met and
      continued until transfusion independence (TI). Kaplan-Meier statistics and Cox
      Proportional Hazard models were used to assess relationships between time to ESA
      initiation, agent and number of weeks of ESA use and TI attainment. RESULTS: Of
      610 TD patients treated with ESAs, 210 (34.4%) achieved TI. Median time from ESA
      initiation to TI was 13 weeks. Shorter time from TD to ESA initiation and use of
      darbepoetin were associated with higher probability of achieving TI. The
      probability of achieving TI decreased beyond 8 weeks of treatment, and was very
      low beyond 16 weeks (8-15 weeks: HR=0.64, 16-31 weeks: HR=0.25, 32+ weeks
      HR=0.10). CONCLUSIONS: In this observational, population-based study, variations
      in ESA administration impacted response in transfusion-dependent MDS patients,
      with higher response rates with early administration and use of darbepoetin, and
      low response likelihood in non-responders beyond 16 weeks of therapy.

PMID- 25869078
TI  - Enhancing postmarketing surveillance: continuing challenges.

PMID- 25869079
TI  - Adults with autism spectrum disorder as behavior technicians for young children
      with autism: Outcomes of a behavioral skills training program.
AB  - Adults with autism spectrum disorder (ASD), who were interested in working as
      behavior technicians for young children with autism, participated in 2
      experiments. Participants included 5 adults with Asperger syndrome or pervasive
      developmental disorder not otherwise specified, 19 to 23 years old, and 11
      children with autism, 3 to 7 years old. In Experiment 1, training of the adults
      focused on the implementation of mand training via incidental teaching.
      Experiment 2 focused on teaching participants to use discrete-trial training
      (DTT) with children who exhibited problem behavior. Both experiments showed that
      behavioral skills training was effective for teaching the adult participants the
      behavioral procedures needed to teach children with autism. In addition, the
      children acquired skills as a result of training. Results of Experiment 2 further
      demonstrated that the DTT skills generalized across untrained targets and
      children. Social validity ratings suggested that some participants' teaching was
      indistinguishable from that of individuals without ASD. 

PMID- 25869080
TI  - Radiofluorination of PSMA-HBED via Al(18)F(2+) Chelation and Biological
      Evaluations In Vitro.
AB  - PURPOSE: Ga-68-labeled prostate-specific membrane antigen (PSMA) ligands have
      been used clinically for positron emission tomography (PET) imaging of prostate
      cancer. However, F-18-labeled compounds offer several advantages, including the
      potential for delayed imaging, high starting activities enabling multidose
      preparation, and improved spatial resolution in PET. For F-18 labeling of
      peptides conjugated with a suitable chelator, a fast and feasible method is the
      use of [Al(18)F](2+). In the present study, the radiofluorinations of a well
      known PSMA ligand Glu-NH-CO-NH-Lys(Ahx)-HBED-CC (PSMA-HBED) via [Al(18)F](2+)
      were performed with respect to various reaction parameters, along with the
      biological evaluations in a cell experiment. PROCEDURES: [Al(18)F]PSMA-HBED was
      prepared by adding Na[(18)F]F into a vial containing 0.026 MUmol peptide (in 0.05
      M NaOAc buffer) and 0.03 MUmol AlCl3?6H2O (in 0.05 M NaOAc buffer). Then, it was
      stirred at different temperatures from 1 to 30 min. Afterwards, purification was
      carried out by solid phase extraction. Biological evaluations were performed in
      PSMA-positive cell lines LNCaP C4-2, along with a negative control using PC-3
      cell lines. RESULTS: The best labeling results (81 +/- 0.5 %, n = 4) were
      observed with 0.026 MUmol peptide (30  degrees C, 5 min). For preclinical
      experiments, the production of [Al(18)F]PSMA-HBED at 35  degrees C including
      purification by solid phase extraction (SPE) succeeded within 45 min, resulting
      in a radiochemical yield of 49 +/- 1.2 % (decay-corrected, n = 6, radiochemical
      purity >=98 %) at EOS. The labeled peptide revealed serum stability for 4 h as
      well as a promising binding coefficient (K D) value of 10.3 +/- 2.2 nM in cell
      experiments with PSMA-positive LNCaP C4-2 cells. CONCLUSION: An efficient and one
      pot method for the radiosynthesis of [Al(18)F]PSMA-HBED was developed (0.26 MUmol
      of precursor at 35  degrees C). In cell culture studies, the K D suggests
      [Al(18)F]PSMA-HBED as a potential PSMA ligand for future investigations in vivo
      and clinical applications afterwards.

PMID- 25869081
TI  - Residualization Rates of Near-Infrared Dyes for the Rational Design of Molecular
      Imaging Agents.
AB  - PURPOSE: Near-infrared (NIR) fluorescence imaging is widely used for tracking
      antibodies and biomolecules in vivo. Clinical and preclinical applications
      include intraoperative imaging, tracking therapeutics, and fluorescent labeling
      as a surrogate for subsequent radiolabeling. Despite their extensive use, one of
      the fundamental properties of NIR dyes, the residualization rate within cells
      following internalization, has not been systematically studied. This rate is
      required for the rational design of probes and proper interpretation of in vivo
      results. PROCEDURES: In this brief report, we measure the cellular
      residualization rate of eight commonly used dyes encompassing three core
      structures (cyanine, boron-dipyrromethene (BODIPY), and
      oxazine/thiazine/carbopyronin). RESULTS: We identify residualizing (half-life >24
      h) and non-residualizing (half-life <24 h) dyes in both the far-red (~650-680 nm)
      and near-infrared (~740-800 nm) regions. CONCLUSIONS: This data will allow
      researchers to independently and rationally select the wavelength and
      residualizing nature of dyes for molecular imaging agent design.

PMID- 25869082
TI  - The paradox of surgical management of patients with low-flow, low-gradient aortic
      stenosis.

PMID- 25869083
TI  - The changing scene of preoperative coronary diagnostics.

PMID- 25869084
TI  - Extracorporeal life support in cardiogenic shock: Impact of acute versus chronic
      etiology on outcome.
AB  - BACKGROUND: The role of extracorporeal life support (ECLS) in primary cardiogenic
      shock (PCS) is well established. In this study, we evaluated the impact of
      etiology on outcomes. METHODS: Between January 2009 and March 2013, we implanted
      a total of 249 patients with ECLS; we focused on 64 patients for whom peripheral
      ECLS was the treatment for PCS. Of these, 37 cases (58%) were "acute" (mostly
      acute myocardial infarction: 39%); 27 (42%) had an exacerbation of "chronic"
      heart failure (dilated cardiomyopathy: 30%; post-ischemic cardiomyopathy: 9%; and
      congenital: 3%). RESULTS: In the group with chronic etiology, 23 patients were
      bridged to a left ventricular assist device (52%) or heart transplantation (33%).
      In the group with acute etiology, ECLS was used as a bridge-to-transplantation in
      3 patients (8%), a bridge-to-bridge in 9 (24%), and a bridge-to-recovery in 18
      (49%). One patient in each group was bridged to conventional surgery. Recovery of
      cardiac function was achieved in only the group with acute primary cardiogenic
      shock (18 vs 0 patients, P = .0001). A mean flow during support of <=60% of the
      theoretic flow (body surface area * 2.4) was a predictor of successful weaning (P
      = .02). Median duration of ECLS support was 7 days (range: 2-11.5 days). Nine
      patients (14%) died during support; 30-day overall survival was 80% (51 of 64
      patients); and 59% of patients were discharged, in whom survival at 48 months was
      90%. Thirty-day survival was correlated with duration of ECLS support.
      CONCLUSIONS: In "chronic" heart failure, ECLS represents a bridge to a
      ventricular assist device or heart transplantation, whereas in "acute" settings,
      it offers a considerable chance of recovery, and is often the only required
      therapy.

PMID- 25869085
TI  - Outcomes of surgical aortic valve replacement for severe aortic stenosis:
      Incorporation of left ventricular systolic function and stroke volume index.
AB  - OBJECTIVES: We sought to assess predictors of mortality in consecutive patients
      with severe aortic stenosis undergoing aortic valve replacement and to determine
      whether there are differences in mortality, separated on the basis of different
      aortic stenosis subtypes and left ventricular stroke volume index. METHODS: We
      studied 875 patients (aged 69 +/- 12 years, 67% were men) with severe aortic
      stenosis (aortic valve area <= 1 cm(2)) who underwent aortic valve replacement
      between January 2007 and December 2008 (excluding other severe valve disease,
      balloon aortic valvuloplasty, and transcatheter aortic valve replacement).
      Clinical and echocardiographic data were recorded. Left ventricular stroke volume
      index was measured as left ventricular outflow tract velocity time integral *
      left ventricular outflow tract area/body surface area. Patients were classified
      into the following subtypes: (1) standard severe (n = 536, left ventricular
      ejection fraction >= 50% and mean gradient >= 40 mm Hg); (2) paradoxic severe (n
      = 152, left ventricular ejection fraction >= 50%, mean gradient <40 mm Hg and
      left ventricular stroke volume index <35 mL/m(2)); and (3) low left ventricular
      ejection fraction severe (n = 187, ejection fraction <50%). Society of Thoracic
      Surgeons score and all-cause mortality were recorded. RESULTS: At 4.8 +/- 2
      years, 153 patients (18%) died (30-day mortality 1.8%). On multivariable Cox
      analysis, age (hazard ratio [HR], 1.49), New York Heart Association class (HR,
      1.52), prior cardiac surgery (HR, 1.41), aortic stenosis subtypes (standard
      severe reference HR, 1; paradoxic severe HR, 1.48; and low left ventricular
      ejection fraction severe HR, 2.03), and reduced glomerular filtration rate (HR,
      1.17) were associated with higher long-term mortality (P < .05). CONCLUSIONS: In
      patients with severe aortic stenosis undergoing aortic valve replacement,
      patients with standard severe aortic stenosis had better long-term survival than
      those with paradoxic severe or low left ventricular ejection fraction severe
      aortic stenosis.

PMID- 25869086
TI  - Time, it needs time.

PMID- 25869087
TI  - When is palliation permanent?

PMID- 25869088
TI  - A reinforced right-ventricle-to-pulmonary-artery conduit for the stage-1 Norwood
      procedure improves pulmonary artery growth.
AB  - OBJECTIVE: To compare early postoperative outcomes, angiographic, and
      intervention findings and 1-year survival between 2 groups of infant patients:
      those receiving a standard right-ventricle-to-pulmonary-artery (RV-PA) conduit
      versus a ring-reinforced RV-PA conduit, in undergoing Norwood stage-1 surgery for
      hypoplastic left heart syndrome (HLHS). The technique of using such a ring
      reinforced graft, placed through a limited ventriculotomy, has theoretic
      advantages in preserving right ventricular function, compared with the standard
      technique of RV-PA conduit creation. METHODS: This retrospective cohort study was
      performed between July 2006 and July 2013. A total of 87 patients with HLHS
      underwent Norwood stage-1 surgery during this period; 48 received a standard
      nonreinforced RV-PA conduit; 39 received a ring-reinforced conduit. Primary and
      secondary outcomes were survival and need for cardiac reintervention up to age 12
      months. RESULTS: No difference was found in transplant-free survival by age 12
      months (87% ring-reinforced vs 73% nonreinforced, P = .12). The group with the
      nonreinforced, versus ring-reinforced, grafts had more interventions in the first
      year (69% vs 35%, respectively; P < .01). Before stage 2, the pulmonary artery
      pulse pressure was greater in the group with ring-reinforced grafts (9.1 +/- 4.1
      vs 4.8 +/- 3.1 mm Hg, P < .001), with no difference in mean pressure (15.2 +/-
      3.32 vs 14.3 +/- 3.48 mm Hg, P = .27). The corrected pulmonary artery index
      (Nakata) was greater in the group with ring-reinforced grafts (213 +/- 76 vs 134
      +/- 68 mm(2)/m(2), P < .0001). CONCLUSIONS: A ring-reinforced conduit is
      associated with reduced intervention, as well as higher pulse pressures and
      improved pulmonary artery growth, in infants undergoing stage-1 palliation for
      HLHS.

PMID- 25869089
TI  - Valve-in-valve transcatheter aortic valve implantation for failing surgical
      aortic stentless bioprosthetic valves: A single-center experience.
AB  - BACKGROUND: Valve-in-valve (ViV) transcatheter aortic implantation (TAVI) is an
      alternative to redo surgery for patients with a failing aortic bioprosthesis. A
      lack of anatomic markers may complicate the procedure. This study reports
      procedural and midterm outcomes of patients undergoing ViV-TAVI for failing
      stentless bioprostheses, at a single institution. METHODS: A total of 22
      consecutive patients with failing homograft (n = 17), stented porcine valve (n =
      3), aortic root bioprosthesis (n = 1), or native resuspended aortic valve (n = 1)
      (aged 74 +/- 12 years; Society of Thoracic Surgeons 30-day predicted risk of
      mortality score: 14% +/- 8%) were treated with ViV-TAVI, between 2007 and 2014.
      All had severe aortic regurgitation and were highly symptomatic before TAVI: 41%
      had chronic kidney disease; 32% had undergone previous coronary bypass grafts;
      27% had previous percutaneous coronary intervention; 14% had severe pulmonary
      disease; 14% had had a stroke. All underwent TAVI with a self-expanding device.
      RESULTS: The 30-day mortality was 0%. No cases occurred of myocardial infarction,
      tamponade, stroke, severe bleeding, acute kidney injury, or major vascular
      complications. Three instances of device migration, and 1 of device embolization,
      occurred. Permanent pacing was required in 14%. Paravalvular aortic regurgitation
      was absent or mild in 19, and mild to moderate in 3. Average hospital stay was 8
      +/- 3 days; all patients were discharged home. Six-month and 1-year mortality was
      4.8% and 14.3%, respectively. Aortic valve area and paravalvular aortic
      regurgitation were unchanged at 1 year. CONCLUSIONS: The ViV-TAVI procedure may
      be performed in high-risk patients with a degenerate stentless bioprosthesis with
      low 30-day mortality, and 1-year mortality of 14.3%. Although technically
      challenging, owing to a lack of anatomic markers, satisfactory positioning is
      possible in most cases, with excellent clinical and echocardiographic outcomes.

PMID- 25869090
TI  - Geochemical assessment of metal pollution and ecotoxicology in sediment cores
      along Karachi Coast, Pakistan.
AB  - This paper is an attempt to compare the pollution status in two sediment cores,
      one from a polluted site (Ghizri Creek) and another from a relatively unpolluted
      site (Sandspit). Sediment cores (45 cm in length) from coastal locations were
      characterized in terms of grain size, sediment composition, pH, organic matter,
      calcium carbonate, and metal element contents. Metal elements, including Al, Ca,
      Cr, Co Cu, Fe, K, Mg, Mn, Ni, Pb, V, Ti, and Zn, were determined using PIXE.
      Grain size analysis and sediment composition demonstrated a sandy nature of both
      cores. Acidic trend in sediment core I was predominant from bottom to top,
      whereas neutral pH was observed throughout core II. TOC values varied in the
      range of 1.23-2.68 and 1.14-2.60% in core I and core II, respectively; however,
      there was an increasing trend in TOC level from bottom to top. The values of
      enrichment factor for Zn, Cu, Co, Ni, Pb, and Cr were slightly higher in core I
      than core II. The average geo-accumulation index values for core I and core II
      showed that sediments were moderately Co- and Pb-polluted but not polluted with
      Mg, Al, Ca, K, Cr, Cu, Fe, Mn, Ni, Ti, V, and Zn. The degree of contamination was
      however considerably higher in core I relative to core II. The pollution load
      index values, although showing an increasing trend from bottom to top in both
      cores, overall rendered the marine sediment pollution free. The metal toxicology
      results demonstrated that heavy metal pollution, except Cr, may pose low to
      moderate risk to marine biota. The sum of toxic unit values however indicated
      that sediment core I was relatively more polluted than that of core II.

PMID- 25869091
TI  - A comparison between determination of trace amounts of sulfide in the presence
      and absence of micelle particles in natural waters (Qazvin, Iran): a kinetic
      spectrophotometric approach.
AB  - A new sensitive kinetic spectrophotometric method described for the determination
      of trace amounts of sulfides based on the addition reaction of sulfide ions with
      malachite green has been investigated in aqueous and micellar media at 25 
      degrees C. The variables affecting the rate of the reaction were investigated,
      and the optimum conditions were established. Under the optimum experimental
      conditions, decreases in the absorbance of malachite green at 615 nm in the
      absence and 630 nm in the presence of micelle particles, their lambda max, were
      proportional to the concentrations of sulfide ions at the first 15 and 25 s from
      initiation of the reaction. The working curve was linear over the concentration
      range 50-1200 ng mL(-1) of sulfide ions with a fixed time method at the first 15
      and 25 s from initiation of the reaction in aqueous medium and 25-1750 ng mL(-1)
      with a fixed time method at the first 15 s and 25-1500 ng mL(-1) for primitive 25
      s in micellar medium. For the proposed kinetic method, the experimental and
      theoretical limit of detection (LOD) and limit of quantification (LOQ) in the
      presence and absence of micelle particles were obtained and tabulated at Deltat =
      15 and 25 s. The effective range concentration was achieved from the plot of
      Ringbom in both media and reported. Different surfactants, such as nonionic
      surfactant (Triton-X100), anionic surfactant sodium dodecyl sulfate (SDS), and
      cationic surfactant cetyltrimethylammonium bromide (CTAB) and cetylpyridinium
      chloride (CPC), were investigated and Triton X-100 selected as a suitable
      surfactant. To valuable vision into the reaction pathways, pseudo-first-order
      condition was applied and different kinetic parameters like DeltaG (?), DeltaE
      (?), DeltaS (?), and DeltaH (?) computed. The 2:1 stoichiometry of malachite
      green to sulfide ions was indicated by the results of mole ratio and Job's method
      of continuous variation. The effect of different environments on the interfering
      of various ions on sulfide determination with the suggested method was studied,
      and final results have been presented. To investigate the usefulness of the
      different media of the proposed method, sulfide ions were determined in natural
      waters such as river and spring samples without any purification or using masking
      reagents. 

PMID- 25869092
TI  - A high performance photothermal film with spherical shell-type metallic
      nanocomposites for solar thermoelectric conversion.
AB  - A photothermal film (PTF) with densely assembled gold nanoparticle-fixed beads on
      a polymer substrate is fabricated. Remarkably, a temperature rise higher than 40 
      degrees C is achieved in the PTF with only 100 seconds of artificial solar
      irradiation, and the output power of the thermoelectric device was enhanced to be
      one order higher than that without PTF. These results will pioneer a rapid solar
      thermoelectric device. 

PMID- 25869093
TI  - Australian Institute of Sport and the Australian Paralympic Committee position
      statement: urinary tract infection in spinal cord injured athletes.
AB  - Patients with spinal cord injuries are at increased risk of developing
      symptomatic urinary tract infections. Current evidence-based knowledge regarding
      prevention and treatment of urinary tract infection in the spinal cord injured
      population is limited. There are currently no urinary tract infection prevention
      and management guidelines specifically targeted towards elite spinal cord injured
      athletes. This position statement represents a set of recommendations intended to
      provide clinical guidelines for sport and exercise medicine physicians and other
      healthcare providers for the prevention and treatment of urinary tract infection
      in spinal cord injured athletes. It has been endorsed by the Australian Institute
      of Sport (AIS) and the Australian Paralympic Committee (APC). 

PMID- 25869094
TI  - What's the big deal about T-wave inversion in athletes? A guide to clinical
      interpretation.

PMID- 25869095
TI  - Unique case of epidermoid cyst located in the omentum.
AB  - Cystic lesions deriving from the omentum are rare benign clinical conditions of
      uncertain etiopathogenesis. In this report we describe a case of antenatal
      diagnosed intra-abdominal cystic mass, which, due to the absence of
      symptomatology and constant ultrasound morphology over time, did not require
      immediate treatment. The present patient was followed up until surgery, which was
      performed at 4 years of age: on laparoscopy a cyst within the greater omentum was
      identified and excised. Histopathology indicated a cyst with epidermoid
      structure, which is unusual among the omental cysts reported in the literature. 

PMID- 25869096
TI  - Functional Proteomics Study Reveals SUMOylation of TFII-I is Involved in Liver
      Cancer Cell Proliferation.
AB  - SUMOylation has emerged as a new regulatory mechanism for proteins involved in
      multiple physiological and pathological processes. However, the detailed function
      of SUMOylation in liver cancer is still elusive. This study reveals that the
      SUMOylation-activating enzyme UBA2 is highly expressed in liver cancer cells and
      clinical samples. Silencing of UBA2 expression could to some extent suppress cell
      proliferation. To elucidate the function of UBA2, we used a large scale
      proteomics strategy to identify SUMOylation targets in HepG2 cells. We
      characterized 827 potential SUMO1-modified proteins that were not present in the
      control samples. These proteins were enriched in gene expression processes.
      Twelve candidates were validated as SUMO1-modified proteins by
      immunoprecipitation-Western blotting. We further characterized SUMOylated protein
      TFII-I that was identified in this study and determined that TFII-I was modified
      by SUMO1 at K221 and K240. PIAS4 was an E3 ligase for TFII-I SUMOylation, and
      SENP2 was responsible for deSUMOylating TFII-I in HepG2 cells. SUMOylation
      reduced TFII-I binding to its repressor HDAC3 and thus promoted its
      transcriptional activity. We further show that SUMOylation is critical for TFII-I
      to promote cell proliferation and colony formation. Our findings contribute to
      understanding the role of SUMOylation in liver cancer development. 

PMID- 25869098
TI  - MicroRNA profiling of Chinese primary glioblastoma reveals a temozolomide
      chemoresistant subtype.
AB  - Accumulating evidence demonstrates that defining molecular subtypes based on
      objective genetic alterations may permit a more rational, patient-specific
      approach to molecular targeted therapy across various cancers. The objective of
      this study was to subtype primary glioblastoma (pGBM) based on MicroRNA (miRNA)
      profiling in Chinese population. Here, miRNA expression profiles from 82 pGBM
      samples were analyzed and 78 independent pGBM samples were used for qRT-PCR
      validation. We found that two distinct subgroups with different prognosis and
      chemosensitivities to temozolomide (TMZ) in Chinese pGBM samples. One subtype is
      TMZ chemoresistant (termed the TCR subtype) and confers a poor prognosis. The
      other subtype is TMZ-chemosensitive (termed the TCS subtype) and confers a
      relatively better prognosis compared with the TCR subtype. A classifier
      consisting of seven miRNAs was then identified (miR-1280, miR-1238, miR-938 and
      miR-423-5p (overexpressed in the TCR subtype); and let-7i, miR-151-3p and miR-93
      (downregulated in the TCR subtype)), which could be used to assign pGBM samples
      to the corresponding subtype. The classifier was validated using both internal
      and external samples. Meanwhile, the genetic alterations of the TCR and TCS
      subtypes were also analyzed. The TCR subtype was characterized by no IDH1
      mutation, and EGFR and Ki-67 overexpression. The TCS subtype displayed the
      opposite situation. Taken together, the results indicate a distinct subgroup with
      poor prognosis and TMZ-chemoresistance. 

PMID- 25869099
TI  - B-cell precursor acute lymphoblastic leukemia and stromal cells communicate
      through Galectin-3.
AB  - The molecular interactions between B-cell precursor acute lymphoblastic leukemia
      (pre-B ALL) cells and stromal cells in the bone marrow that provide
      microenvironmentally-mediated protection against therapeutic drugs are not well
      defined. Galectin-3 (Lgals3) is a multifunctional galactose-binding lectin with
      reported location in the nucleus, cytoplasm and extracellular space in different
      cell types. We previously reported that ALL cells co-cultured with stroma contain
      high levels of Galectin-3. We here establish that, in contrast to more mature B
      lineage cancers, Galectin-3 detected in and on the ALL cells originates from
      stromal cells, which express it on their surface, secrete it as soluble protein
      and also in exosomes. Soluble and stromal-bound Galectin-3 is internalized by ALL
      cells, transported to the nucleus and stimulates transcription of endogenous
      LGALS3 mRNA. When human and mouse ALL cells develop tolerance to different drugs
      while in contact with protective stromal cells, Galectin-3 protein levels are
      consistently increased. This correlates with induction of Galectin-3
      transcription in the ALL cells. Thus Galectin-3 sourced from stroma becomes
      supplemented by endogenous Galectin-3 production in the pre-B ALL cells that are
      under continuous stress from drug treatment. Our data suggest that stromal
      Galectin-3 may protect ALL cells through auto-induction of Galectin-3 mRNA and
      tonic NFkappaB pathway activation. Since endogenously synthesized Galectin-3
      protects pre-B ALL cells against drug treatment, we identify Galectin-3 as one
      possible target to counteract the protective effects of stroma. 

PMID- 25869100
TI  - Inhibition of beta-catenin signaling suppresses pancreatic tumor growth by
      disrupting nuclear beta-catenin/TCF-1 complex: critical role of STAT-3.
AB  - Aberrant activation of beta-catenin/TCF signaling is related to the invasiveness
      of pancreatic cancer. In the present study, we evaluated the effect of capsaicin
      on beta-catenin/TCF signaling. In a concentration and time-dependent study, we
      observed that capsaicin treatment inhibits the activation of dishevelled (Dsh)
      protein DvI-1 in L3.6PL, PanC-1 and MiaPaCa-2 pancreatic cancer cells. Capsaicin
      treatment induced GSK-3beta by inhibiting its phosphorylation and further
      activated APC and Axin multicomplex, leading to the proteasomal degradation of
      beta-catenin. Expression of TCF-1 and beta-catenin-responsive proteins, c-Myc and
      cyclin D1 also decreased in response to capsaicin treatment. Pre-treatment of
      cells with MG-132 blocked capsaicin-mediated proteasomal degradation of beta
      catenin. To establish the involvement of beta-catenin in capsaicin-induced
      apoptosis, cells were treated with LiCl or SB415286, inhibitors of GSK-3beta. Our
      results reveal that capsaicin treatment suppressed LiCl or SB415286-mediated
      activation of beta-catenin signaling. Our results further showed that capsaicin
      blocked nuclear translocation of beta-catenin, TCF-1 and p-STAT-3 (Tyr705). The
      immunoprecipitation results indicated that capsaicin treatment reduced the
      interaction of beta-catenin and TCF-1 in the nucleus. Moreover, capsaicin
      treatment significantly decreased the phosphorylation of STAT-3 at Tyr705.
      Interestingly, STAT-3 over expression or STAT-3 activation by IL-6, significantly
      increased the levels of beta-catenin and attenuated the effects of capsaicin in
      inhibiting beta-catenin signaling. Finally, capsaicin mediated inhibition of
      orthotopic tumor growth was associated with inhibition of beta-catenin/TCF-1
      signaling. Taken together, our results suggest that capsaicin-induced apoptosis
      in pancreatic cancer cells was associated with inhibition of beta-catenin
      signaling due to the dissociation of beta-catenin/TCF-1 complex and the process
      was orchestrated by STAT-3. 

PMID- 25869097
TI  - Chronic myelomonocytic leukemia: Forefront of the field in 2015.
AB  - Chronic myelomonocytic leukemia (CMML) includes components of both
      myelodysplastic syndrome and myeloproliferative neoplasms and is associated with
      a characteristic peripheral monocytosis. CMML is caused by the proliferation of
      an abnormal hematopoietic stem cell clone and may be influenced by
      microenvironmental changes. The disease is rare and has undergone revisions in
      its classification. We review the recent classification strategies as well as
      diagnostic criteria, focusing on CMML's genetic alterations and unique
      pathophysiology. We also discuss the latest molecular characterization of the
      disease, including how molecular factors affect current prognostic models.
      Finally, we focus on available treatment strategies, with a special emphasis on
      experimental and forthcoming therapies. 

PMID- 25869101
TI  - microRNA-217 inhibits tumor progression and metastasis by downregulating EZH2 and
      predicts favorable prognosis in gastric cancer.
AB  - microRNA-217 (miR-217) is frequently dysregulated in cancer. Here, we report that
      miR-217 levels were lower in tumor tissue compared with the adjacent normal
      tissue. Low levels of miR-217 were associated with aggressive tumor phenotypes
      and poor overall survival in gastric cancer patients. The ectopic expression of
      miR-217 inhibited cell proliferation, migration and invasion in vitro and tumor
      growth and metastasis in vivo, whereas knockdown of endogenous miR-217 increased
      cell proliferation and invasion. Further experiments revealed that Polycomb group
      protein enhancer of zeste homolog 2 (EZH2) was a direct target of miR-217 in
      gastric cancer cells. Knockdown of EZH2 mimicked the tumor-suppressive effects of
      miR-217 in gastric cancer cells, whereas the reintroduction of EZH2 abolished its
      effects. Taken together, these results demonstrated that miR-217 may be used as a
      prognostic marker, and the newly identified miR-217-EZH2 axis may be a potential
      target in the development of therapeutic strategies for gastric cancer patients. 

PMID- 25869103
TI  - Hypertension exacerbates predisposition to neurodegeneration and memory
      impairment in the presence of a neuroinflammatory stimulus: Protection by
      angiotensin converting enzyme inhibition.
AB  - Hypertension is a risk factor for cognitive impairment. Furthermore,
      neuroinflammation and neurodegeneration are intricately associated with memory
      impairment. Therefore, the present study aimed to explore the involvement of
      hypertension and angiotensin system in neurodegeneration and memory dysfunction
      in the presence of neuroinflammatory stimulus. Memory impairment was induced by
      chronic neuroinflammation that was developed by repeated intracerebroventricular
      (ICV) injections of lipopolysaccharide (LPS) on the 1st, 4th, 7th, and 10th day.
      Memory functions were evaluated by the Morris water maze (MWM) test on days 13
      15, followed by biochemical and molecular studies in the cortex and hippocampus
      regions of rat brain. LPS at the dose of 25MUg ICV caused memory impairment in
      spontaneously hypertensive rats (SHRs) but not in normotensive Wistar rats
      (NWRs). Memory deficit was obtained with 50MUg of LPS (ICV) in NWRs. Control SHRs
      already exhibited increased angiotensin converting enzyme (ACE) activity and
      expression, neuroinflammation (increased TNF-alpha, GFAP, COX-2 and NF-kB),
      oxidative stress (increased iNOS, ROS and nitrite levels), TLR-4 expression and
      TUNEL positive cells as compared to control NWRs. Further, LPS (25MUg ICV)
      exaggerated inflammatory response, oxidative stress and apoptosis in SHRs but
      similar effects were witnessed at 50MUg of LPS (ICV) in NWRs. Oral administration
      of perindopril (ACE inhibitor), at non-antihypertensive dose (0.1mg/kg), for
      15days attenuated LPS induced deleterious changes in both NWRs and SHRs. Our data
      suggest that susceptibility of the brain for neurodegeneration and memory
      impairment induced by neuroinflammation is enhanced in hypertension, and that can
      be protected by ACE inhibition. 

PMID- 25869104
TI  - Complex proximal ulna fractures: outcomes of surgical treatment.
AB  - BACKGROUND: To review the results of plating of various fracture patterns of
      proximal ulna fractures including isolated olecranon fractures, olecranon
      fractures combined with a coronoid fracture, and olecranon fractures combined
      with a coronoid and radial head fracture. MATERIALS AND METHODS: The study
      included 38 patients with either an isolated olecranon fracture or combined
      injuries, all treated with open reduction and internal fixation of the olecranon.
      Other procedures were performed as needed, including radial head fixation or
      arthroplasty, fixation of the coronoid, and repair of the lateral collateral
      ligament complex. There were 27 men and 11 women with an average age of 49 years.
      Clinical and radiographic assessment was obtained at an average follow-up time of
      15 and 8.4 months, respectively. RESULTS: All fractures healed within 5 months.
      The average arc of ulnohumeral motion was 91 degrees  (range 0 degrees -140
      degrees ); average pronation-supination arc was 128 degrees  (range 0 degrees 
      180 degrees ). Subgroup analysis showed a statistically significant lower
      rotational motion arc in patients with associated radial head (73 degrees ) or
      coronoid fractures (68 degrees ) compared to isolated olecranon fractures. All
      other parameters including ulnohumeral motion, complication rate, and revision
      rate were similar among the groups. CONCLUSIONS: A stable, functional elbow can
      be restored in most patients with proximal ulna fractures treated with open
      reduction and internal fixation. Loss of full flexion is likely with high-energy
      trauma, complex fracture patterns, and concomitant injuries. Fracture patterns
      involving the coronoid and/or the radial head are associated with restricted
      forearm rotation. LEVEL OF EVIDENCE: III.

PMID- 25869102
TI  - Targeted therapies for advanced Ewing sarcoma family of tumors.
AB  - The prognosis of adolescent and young adult patients battling metastatic Ewing
      sarcoma family of tumors (ESFT) remains less than 30% despite the development of
      systemic therapies. In the era of personalized medicine, novel molecular targets
      have been tested in preclinical or clinical settings in ESFT. In this review, we
      focus on early clinical and translational research that identified multiple
      molecular targets, including IGF-1R; mTOR; tyrosine kinase inhibitors; EWS-FLI1
      related targets, and others. Overall, novel targeted therapies demonstrated
      modest efficacy; however pronounced and durable antineoplastic responses have
      been observed in small subsets of treated patients, for example with IGF-1R
      antibodies. Identifying outcome-predicting biomarkers and overcoming treatment
      resistance remain major challenges. Due to the rarity of ESFT, multi
      institutional collaboration efforts of clinicians, basic and translational
      scientists are needed in order to understand biology of therapeutic response or
      resistance, which can lead to development of novel therapeutic methods and
      improved patient outcomes.

PMID- 25869105
TI  - Nailing or plating for subtrochanteric femoral fractures: a non-randomized
      comparative study.
AB  - BACKGROUND: The aim of the present study was to compare the outcomes of reverse
      less invasive stabilization system for distal femur (LISS-DF) plates and proximal
      femoral nail antirotation (PFNA) in the treatment of patients with
      subtrochanteric fracture. METHODS: Thirty-one patients with 32 fractures were
      included in this study. The PFNA group consisted of 16 patients, and the reverse
      LISS-DF plate group consisted of 15 patients. Intraoperative data such as
      surgical time (min), amount of blood transfusion (units and erythrocyte
      suspensions) and radiation time (seconds) were noted. Time elapsed until fracture
      consolidation (weeks), time until full weight bearing (weeks), mean Harris hip
      score and length of stay (LOS) at hospital (days) were recorded postoperatively.
      RESULTS: The reverse LISS-DF group had a significantly longer elapsed time until
      fracture consolidation (p < 0.05). The mean radiation time was significantly
      longer (p < 0.05), and the Harris hip scores at last control were significantly
      higher (p < 0.05) compared with the PFNA group. No significant differences were
      determined in terms of complications and re-operation rates. CONCLUSION: This
      study demonstrated that in the reverse LISS-DF-treated group, the mean time for
      bone union was longer and weight bearing was delayed. Considering the surgical
      technique, minimal surgical approach, reduced amount of blood transfusion and
      superior functional results following surgery, we concluded that the PFNA system
      offers advantages over reverse LISS-DF plating in the treatment of
      subtrochanteric femur fractures.

PMID- 25869106
TI  - Differences between the alpha angles measured manually and digitally from
      paediatric hip ultrasonograms.
AB  - The aim of this study was to reveal whether a meaningful difference is caused by
      measuring the alpha angle in hip ultrasonography manually or digitally to help
      the early diagnosis and treatment of DDH and observe the treatment implications
      of any such difference. All ultrasound images were obtained by same orthopaedist,
      and each hip was measured twice by two investigators with different levels of
      experience. Standard images were taken, and a printout of the standard images
      were obtained. The alpha angle was measured digitally by using the sonography
      device. The alpha angle was also measured by pencil, ruler and goniometer on the
      printout after 2 days. One hundred and two hips of 51 babies, at a mean age of 14
      weeks, were assessed. The mean alpha angle measured manually with a goniometer
      was 64.4 degrees  (+/-1.6 degrees ), while that measured on the ultrasonography
      device was 65.3 degrees  (+/-0.9 degrees ). This difference was found to be
      statistically different (p = 0.016). Typology changes occurred in a total of 10
      hips out of 102 as a result of manual and digital measurements. However, this
      study showed reduction in alpha angle variation and considerable advantages for
      manual alpha angle measurement with pencil and goniometer on a printout compared
      to computer-based measurement; future studies are needed to understand these
      differences caused by each measurement method.

PMID- 25869107
TI  - Isolated pelvic ring injuries: functional outcomes following percutaneous,
      posterior fixation.
AB  - OBJECTIVES: To characterize pelvic-specific functional outcomes in patients with
      isolated, partially unstable (AO/OTA 61-B), pelvic ring injuries treated with
      posterior only percutaneous screw fixation of the pelvic ring. PATIENTS AND
      METHODS: Between September 2007 and October 2011, 16 subjects (mean age 42.4
      years; range 18-90 years) with isolated, partially unstable pelvic ring injuries
      (AO/OTA 61-B) were treated with percutaneous, posterior pelvic ring fixation.
      Subjects underwent an evaluation of pelvic ring function with a modification of
      Majeed's pelvic functional outcome assessment tool. Subjects were excluded if
      they sustained a concomitant long-bone fracture, visceral injury requiring
      surgery, spinal cord injury, and an injury to the anterior pelvic ring or
      acetabulum requiring additional fixation. RESULT: Mean follow-up was 30.8 (range
      14-55) months. Eleven subjects sustained unilateral posterior ring injuries, and
      five subjects sustained bilateral posterior ring injuries. All fractures healed
      uneventfully, and no hardware failures were noted. Average pelvic functional
      outcome score at final follow-up was 85.3 % (good). All but subjects required
      assistive walking devices and gait and sitting comfort scored "excellent." High
      rates of sexual dysfunction and persistent difficulty with daily activities were
      noted in this series. CONCLUSIONS: This series demonstrates that activity
      specific dysfunction persists years after definitive percutaneous posterior
      fixation of isolated pelvic ring injuries. Radiographic outcomes were excellent
      as were subjects' ability to ambulate independently and sit comfortably without
      pain. Many complained of persistent discomfort with both daily activities and
      sexual activity, suggesting persistent pathology to the non-osseous structures
      about the pelvis.

PMID- 25869108
TI  - Extended proximal femoral osteotomy: technical tip.
AB  - Extended proximal femoral osteotomy is a well-established technique in complex
      primary and revision hip surgery. It is commonly indicated for extraction of well
      fixed femoral components either cemented or uncemented. Some of the problems
      encountered during this procedure are gaining an accurate reduction in the
      osteotomized fragment and a stable reduction and fixation. Here, we present a
      modification to the standard surgical technique which aids in anatomical
      reduction and enhances the stability of the reduced fragment. We make the distal
      transverse cut oblique rather than vertical. This modification allows for a more
      stable and anatomical reduction in the osteotomy. Our experience with this
      modified technique demonstrated 100 % union of the osteotomy. 

PMID- 25869109
TI  - Who is the gatekeeper to let inflammation enter the brain? A concerted action of
      endothelial and perivascular cells.

PMID- 25869110
TI  - Transcranial direct current stimulation-induced seizure: analysis of a case.

PMID- 25869111
TI  - Fragmentation mechanisms of cytosine, adenine and guanine ionized bases.
AB  - The different fragmentation channels of cytosine, adenine and guanine have been
      studied through DFT calculations. The electronic structure of bases, their
      cations, and the fragments obtained by breaking bonds provides a good
      understanding of the fragmentation process that can complete the experimental
      approach. The calculations allow assigning various fragments to the given peaks.
      The comparison between the energy required for the formation of fragments and the
      peak intensity in the mass spectrum is used. For cytosine and guanine the
      elimination of the HNCO molecule is a major route of dissociation, while for
      adenine multiple loss of HCN or HNC can be followed up to small fragments. For
      cytosine, this corresponds to the initial bond cleavage of N3-C4/N1-C2, which
      represents the main dissociation route. For guanine the release of HNCO is
      obtained through the N1-C2/C5-C6 bond cleavage (reverse order also possible)
      leading to the largest peak of the spectrum. The corresponding energies of 3.5
      and 3.9 eV are typically in the range available in the experiments. The loss of
      NH3 or HCN is also possible but requires more energy. For adenine, fragmentation
      consists of multiple loss of the HCN molecule and the main route corresponding to
      HC8N9 loss is followed by the release of HC2N1. 

PMID- 25869113
TI  - Analysis of bio-anode performance through electrochemical impedance spectroscopy.
AB  - In this paper we studied the performance of bioanodes under different
      experimental conditions using polarization curves and impedance spectroscopy. We
      have identified that the large capacitances of up to 1 mF.cm(-2) for graphite
      anodes have their origin in the nature of the carbonaceous electrode, rather than
      the microbial culture. In some cases, the separate contributions of charge
      transfer and diffusion resistance were clearly visible, while in other cases
      their contribution was masked by the high capacitance of 1 mF.cm(-2). The
      impedance data were analyzed using the basic Randles model to analyze ohmic,
      charge transfer and diffusion resistances. Increasing buffer concentration from 0
      to 50mM and increasing pH from 6 to 8 resulted in decreased charge transfer and
      diffusion resistances; lowest values being 144 Omega.cm(2) and 34 Omega.cm(2),
      respectively. At acetate concentrations below 1 mM, current generation was
      limited by acetate. We show a linear relationship between inverse charge transfer
      resistance at potentials close to open circuit and saturation (maximum) current,
      associated to the Butler-Volmer relationship that needs further exploration.

PMID- 25869112
TI  - Effects of a Mediterranean Diet Intervention on Anti- and Pro-Inflammatory
      Eicosanoids, Epithelial Proliferation, and Nuclear Morphology in Biopsies of
      Normal Colon Tissue.
AB  - This randomized trial evaluated the effects of intervention with either a Healthy
      Eating or a Mediterranean diet on colon biomarkers in 120 healthy individuals at
      increased colon cancer risk. The hypothesis was that eicosanoids and markers of
      proliferation would be favorably affected by the Mediterranean diet. Colon
      epithelial biopsy tissues and blood samples were obtained at baseline and after 6
      mo of intervention. Colonic eicosanoid concentrations were evaluated by HPLC-MS
      MS, and measures of epithelial proliferation and nuclear morphology were
      evaluated by image analysis of biopsy sections. There was little change in
      proinflammatory eicosanoids and in plasma cytokine concentrations with either
      dietary intervention. There was, however, a 50% increase in colonic prostaglandin
      E3 (PGE3), which is formed from eicosapentanoic acid, in the Mediterranean arm.
      Unlike PGE2, PGE3, was not significantly affected by regular use of non-steroidal
      anti-inflammatory drugs at baseline, and normal weight subjects had significantly
      higher colon PGE3 than overweight or obese subjects. Increased proliferation in
      the colon at baseline, by Ki67 labeling, was associated with morphological
      features that defined smaller nuclei in the epithelial cells, lower colon
      leukotriene concentrations and higher plasma cytokine concentrations. Dietary
      intervention had little effect on measures of epithelial proliferation or of
      nuclear morphology. The increase in PGE3 with a Mediterranean diet indicates that
      in normal colon, diet might affect protective pathways to a greater extent than
      proinflammatory and proliferative pathways. Hence, biomarkers from cancer models
      might not be relevant in a true prevention setting. 

PMID- 25869114
TI  - Physical chemistry of highly concentrated emulsions.
AB  - This review explores the physics underlying the rheology of highly concentrated
      emulsions (HCEs) to determine the relationship between elasticity and HCE
      stability, and to consider whether it is possible to describe all physicochemical
      properties of HCEs on the basis of a unique physical approach. We define HCEs as
      emulsions with a volume fraction above the maximum closest packing fraction of
      monodisperse spheres, phim=0.74, even if droplets are not of polyhedron shape.
      The solid-like rheological behavior of HCEs is characterized by yield stress and
      elasticity, properties which depend on droplet polydispersity and which are
      affected by caging at volume fractions about the jamming concentration, phij. A
      bimodal size distribution in HCEs diminishes caging and facilitates droplet
      movement, resulting in HCEs with negligible yield stress and no plateau in
      storage modulus. Thermodynamic forces automatically move HCEs toward the lowest
      free energy state, but since interdroplet forces create local minimums - points
      beyond which free energy temporarily increases before it reaches the global
      minimum of the system - the free energy of HCEs will settle at a local minimum
      unless additional energy is added. Several attempts have been undertaken to
      predict the elasticity of HCEs. In many cases, the elastic modulus of HCEs is
      higher than the one predicted from classical models, which only take into account
      spatial repulsion (or simply interfacial energy). Improved models based on free
      energy calculation should be developed to consider the disjoining pressure and
      interfacial rheology in addition to spatial repulsion. The disjoining pressure
      and interfacial viscoelasticity, which result in the deviation of elasticity from
      the classical model, can be regarded as parameters for quantifying the stability
      of HCEs. 

PMID- 25869115
TI  - Deciphering the alternatively activated (M2) phenotype of macrophages in
      scleroderma.

PMID- 25869116
TI  - Cyclopentapeptides from Dianthus chinensis.
AB  - A new cyclopentapeptide dianthin I (1), together with two known ones
      pseudostellarin A (2) and heterophyllin J (3), was isolated from the aerial parts
      of Dianthus chinensis. The structure of 1 was elucidated as cyclo-(Gly(1)-L
      Phe(2)-L-Pro(3)-L-Ser(4)-L-Phe(5)) on the basis of extensive spectroscopic
      analyses and chemical methods.

PMID- 25869117
TI  - Space-time cluster analysis of sea lice infestation (Caligus clemensi and
      Lepeophtheirus salmonis) on wild juvenile Pacific salmon in the Broughton
      Archipelago of Canada.
AB  - Sea lice infestation levels on wild chum and pink salmon in the Broughton
      Archipelago region are known to vary spatially and temporally; however, the
      locations of areas associated with a high infestation level had not been
      investigated yet. In the present study, the multivariate spatial scan statistic
      based on a Poisson model was used to assess spatial clustering of elevated sea
      lice (Caligus clemensi and Lepeophtheirus salmonis) infestation levels on wild
      chum and pink salmon sampled between March and July of 2004 to 2012 in the
      Broughton Archipelago and Knight Inlet regions of British Columbia, Canada. Three
      covariates, seine type (beach and purse seining), fish size, and year effect,
      were used to provide adjustment within the analyses. The analyses were carried
      out across the five months/datasets and between two fish species to assess the
      consistency of the identified clusters. Sea lice stages were explored separately
      for the early life stages (non-motile) and the late life stages of sea lice
      (motile). Spatial patterns in fish migration were also explored using monthly
      plots showing the average number of each fish species captured per sampling site.
      The results revealed three clusters for non-motile C. clemensi, two clusters for
      non-motile L. salmonis, and one cluster for the motile stage in each of the sea
      lice species. In general, the location and timing of clusters detected for both
      fish species were similar. Early in the season, the clusters of elevated sea lice
      infestation levels on wild fish are detected in areas closer to the rivers, with
      decreasing relative risks as the season progresses. Clusters were detected
      further from the estuaries later in the season, accompanied by increasing
      relative risks. In addition, the plots for fish migration exhibit similar
      patterns for both fish species in that, as expected, the juveniles move from the
      rivers toward the open ocean as the season progresses The identification of space
      time clustering of infestation on wild fish from this study can help in targeting
      investigations of factors associated with these infestations and thereby support
      the development of more effective sea lice control measures. 

PMID- 25869118
TI  - Fibrin glue on an aortic cusp detected by transesophageal echocardiography after
      valve-sparing aortic valve replacement: a case report.
AB  - INTRODUCTION: Fibrin glue is used commonly during cardiac surgery but can behave
      as an intracardiac abnormal foreign body following surgery. There have been few
      such cases reported, and they were typically noticed only because of the
      resulting catastrophic cardiac conditions, such as valvular malfunction. We
      report a case where, for the first time, transesophageal echocardiography was
      used to detected fibrin glue that was adherent to the ventricular side of a
      patient's aortic valve immediately after aortic declamping. CASE PRESENTATION: A
      45-year-old Japanese man with Marfan syndrome underwent an aortic valve-sparing
      operation to treat moderate aortic valve regurgitation resulting from enlargement
      of his right coronary cusp. Fibrin glue was lightly applied to the suture line
      between the previous and new grafts. Transesophageal echocardiography performed
      prior to weaning from the cardiopulmonary bypass revealed mild aortic valve
      regurgitation in addition to a mobile membranous structure attached to the
      ventricular side of his aortic valve. It was identified as fibrin glue. We
      resolved the regurgitation by removing the fibrin glue and repeating the aortic
      cusp plication. The patient had no complications during recovery. CONCLUSIONS:
      Fibrin glue can act as an intracardiac foreign body and lead to a potentially
      fatal embolism. We demonstrated the use of transesophageal echocardiography to
      detect a fibrin glue-derived intracardiac abnormal foreign body and to confirm
      its removal. To the best of our knowledge, this is the first case where fibrin
      glue adherent to the aortic valve was detected by transesophageal
      echocardiography. These findings demonstrate the importance of using
      transesophageal echocardiography during cardiac surgery that involves using
      biological glues.

PMID- 25869119
TI  - Patterns and Predictors of Primary Mental Health Service Use Following Bushfire
      and Flood Disasters.
AB  - OBJECTIVE: To examine patterns and predictors of primary mental health care
      service use following 2 major Australian natural disaster events. METHODS:
      Utilizing data from a national minimum dataset, descriptive and regression
      analyses were conducted to identify levels and predictors of the use of the
      Access to Allied Psychological Services (ATAPS) program over a 2-year period
      following 2 major Australian bushfire and flood/cyclone disasters. RESULTS: The
      bushfire disaster resulted in significantly greater and more enduring ATAPS
      service volume, while service delivery for both disasters peaked in the third
      quarter. Consumers affected by bushfires (IRR 1.51, 95% CI 1.20-1.89), diagnosed
      with depression (IRR 2.57, 95% CI 1.60-4.14), anxiety (IRR 2.06, 95% CI 1.21
      3.49), or both disorders (IRR 2.15, 95% CI 1.35-3.42) utilized treatment at
      higher rates. CONCLUSIONS: The substantial demand for primary mental health care
      services following major natural disasters can vary in magnitude and trajectory
      with disaster type. Disaster-specific ATAPS services provide a promising model to
      cater for this demand in primary care settings. Disaster type and need-based
      variables as drivers of ATAPS use intensity indicate an equitable level of
      service use in line with the program intention. Established service usage
      patterns can assist with estimating capacity requirements in similar disaster
      circumstances.

PMID- 25869120
TI  - Agglutination of single catalyst particles during fluid catalytic cracking as
      observed by X-ray nanotomography.
AB  - Metal accumulation at the catalyst particle surface plays a role in particle
      agglutination during fluid catalytic cracking. 

PMID- 25869121
TI  - Interaction-free measurements by quantum Zeno stabilization of ultracold atoms.
AB  - Quantum mechanics predicts that our physical reality is influenced by events that
      can potentially happen but factually do not occur. Interaction-free measurements
      (IFMs) exploit this counterintuitive influence to detect the presence of an
      object without requiring any interaction with it. Here we propose and realize an
      IFM concept based on an unstable many-particle system. In our experiments, we
      employ an ultracold gas in an unstable spin configuration, which can undergo a
      rapid decay. The object-realized by a laser beam-prevents this decay because of
      the indirect quantum Zeno effect and thus, its presence can be detected without
      interacting with a single atom. Contrary to existing proposals, our IFM does not
      require single-particle sources and is only weakly affected by losses and
      decoherence. We demonstrate confidence levels of 90%, well beyond previous
      optical experiments. 

PMID- 25869122
TI  - Cutaneous sarcoidosis with granuloma formation around nerves mimicking
      mycobacterial infection.

PMID- 25869123
TI  - Balloon pulmonary angioplasty for inoperable patients with chronic thromboembolic
      pulmonary hypertension. Preliminary experience in Spain in a series of 7
      patients.

PMID- 25869124
TI  - Prognostic Significance of Heart Rate and its Long-term Trend in Cardiac
      Transplant Patients.
AB  - INTRODUCTION AND OBJECTIVES: The aim of the present study was to examine the
      prognostic significance of heart rate and its trend in heart transplantation.
      METHODS: This observational study enrolled 170 patients who received a bicaval
      heart transplant between 1995 and 2005; all were in sinus rhythm. The resting
      heart rate was determined via electrocardiography at the end of the first
      posttransplant year and annually until the tenth year. Cox analysis was used to
      evaluate the incidence of adverse events with a mean (standard deviation) follow
      up of 8.9 (3.1) years. The primary study end point was the composite outcome of
      death or graft dysfunction. RESULTS: The resting heart rate at the end of the
      first posttransplant year was an independent predictor of the primary composite
      end point (hazard ratio=1.054; 95% confidence interval, 1.028-1.080; P<.001) and
      was significantly associated with total mortality (hazard ratio=1.058; 95%
      confidence interval, 1.030-1.087; P<.001) and mortality from cardiac causes
      (hazard ratio=1.069; 95% confidence interval, 1.026-1.113; P=.001), but not with
      graft dysfunction (hazard ratio=1.028; 95% confidence interval, 0.989-1.069;
      P=.161). For patients with a heart rate >= 105 or<90 bpm vs those with 90-104
      bpm, the hazard ratios of the primary end point were 2.233 (95% confidence
      interval, 1.250-3.989; P=.007) and 0.380 (95% confidence interval, 0.161-0.895;
      P=.027), respectively. Heart rate tended to decrease in the first 10 years after
      transplantation (P=.001). Patients with a net increase in heart rate during
      follow-up showed a higher incidence of adverse events. CONCLUSIONS: An elevated
      heart rate is an adverse prognostic marker after heart transplantation.

PMID- 25869125
TI  - The SNF1 Kinase Ubiquitin-associated Domain Restrains Its Activation, Activity,
      and the Yeast Life Span.
AB  - The enzyme family of heterotrimeric AMP-dependent protein kinases is activated
      upon low energy states, conferring a switch toward energy-conserving metabolic
      pathways through immediate kinase actions on enzyme targets and delayed
      alterations in gene expression through its nuclear relocalization. This family is
      evolutionarily conserved, including the presence of a ubiquitin-associated (UBA)
      motif in most catalytic subunits. The potential for the UBA domain to promote
      protein associations or direct subcellular location, as seen in other UBA
      containing proteins, led us to query whether the UBA domain within the yeast AMP
      dependent protein kinase ortholog, SNF1 kinase, was important in these aspects of
      its regulation. Here, we demonstrate that conserved UBA motif mutations
      significantly alter SNF1 kinase activation and biological activity, including
      enhanced allosteric subunit associations and increased oxidative stress
      resistance and life span. Significantly, the enhanced UBA-dependent longevity and
      oxidative stress response are at least partially dependent on the Fkh1 and Fkh2
      stress response transcription factors, which in turn are shown to influence Snf1
      gene expression. 

PMID- 25869126
TI  - Mechanism of the Association between Na+ Binding and Conformations at the
      Intracellular Gate in Neurotransmitter:Sodium Symporters.
AB  - Neurotransmitter:sodium symporters (NSSs) terminate neurotransmission by Na(+)
      dependent reuptake of released neurotransmitters. Previous studies suggested that
      Na(+)-binding reconfigures dynamically coupled structural elements in an
      allosteric interaction network (AIN) responsible for function-related
      conformational changes, but the intramolecular pathway of this mechanism has
      remained uncharted. We describe a new approach for the modeling and analysis of
      intramolecular dynamics in the bacterial NSS homolog LeuT. From microsecond-scale
      molecular dynamics simulations and cognate experimental verifications in both
      LeuT and human dopamine transporter (hDAT), we apply the novel method to identify
      the composition and the dynamic properties of their conserved AIN. In LeuT, two
      different perturbations disrupting Na(+) binding and transport (i.e. replacing
      Na(+) with Li(+) or the Y268A mutation at the intracellular gate) affect the AIN
      in strikingly similar ways. In contrast, other mutations that affect the
      intracellular gate (i.e. R5A and D369A) do not significantly impair Na(+)
      cooperativity and transport. Our analysis shows these perturbations to have much
      lesser effects on the AIN, underscoring the sensitivity of this novel method to
      the mechanistic nature of the perturbation. Notably, this set of observations
      holds as well for hDAT, where the aligned Y335A, R60A, and D436A mutations also
      produce different impacts on Na(+) dependence. Thus, the detailed AIN generated
      from our method is shown to connect Na(+) binding with global conformational
      changes that are critical for the transport mechanism. That the AIN between the
      Na(+) binding sites and the intracellular gate in bacterial LeuT resembles that
      in eukaryotic hDAT highlights the conservation of allosteric pathways underlying
      NSS function. 

PMID- 25869127
TI  - Microglial Heparan Sulfate Proteoglycans Facilitate the Cluster-of
      Differentiation 14 (CD14)/Toll-like Receptor 4 (TLR4)-Dependent Inflammatory
      Response.
AB  - Microglia rapidly mount an inflammatory response to pathogens in the central
      nervous system (CNS). Heparan sulfate proteoglycans (HSPGs) have been attributed
      various roles in inflammation. To elucidate the relevance of microglial HSPGs in
      a pro-inflammatory response we isolated microglia from mice overexpressing
      heparanase (Hpa-tg), the HS-degrading endoglucuronidase, and challenged them with
      lipopolysaccharide (LPS), a bacterial endotoxin. Prior to LPS-stimulation, the
      LPS-receptor cluster-of-differentiation 14 (CD14) and Toll-like receptor 4 (TLR4;
      essential for the LPS response) were similarly expressed in Ctrl and Hpa-tg
      microglia. However, compared with Ctrl microglia, Hpa-tg cells released
      significantly less tumor necrosis factor-alpha (TNFalpha), essentially failed to
      up-regulate interleukin-1beta (IL1beta) and did not initiate synthesis of
      proCD14. Isolated primary astroyctes expressed TLR4, but notably lacked CD14 and
      in contrast to microglia, LPS challenge induced a similar TNFalpha response in
      Ctrl and Hpa-tg astrocytes, while neither released IL1beta. The astrocyte
      TNFalpha-induction was thus attributed to CD14-independent TLR4 activation and
      was unaffected by the cells HS status. Equally, the suppressed LPS-response in
      Hpa-tg microglia indicated a loss of CD14-dependent TLR4 activation, suggesting
      that microglial HSPGs facilitate this process. Indeed, confocal microscopy
      confirmed interactions between microglial HS and CD14 in LPS-stimulated microglia
      and a potential HS-binding motif in CD14 was identified. We conclude that
      microglial HSPGs facilitate CD14-dependent TLR4 activation and that heparanase
      can modulate this mechanism. 

PMID- 25869128
TI  - Differences in Hematopoietic Stem Cells Contribute to Sexually Dimorphic
      Inflammatory Responses to High Fat Diet-induced Obesity.
AB  - Women of reproductive age are protected from metabolic disease relative to
      postmenopausal women and men. Most preclinical rodent studies are skewed toward
      the use of male mice to study obesity-induced metabolic dysfunction because of a
      similar protection observed in female mice. How sex differences in obesity
      induced inflammatory responses contribute to these observations is unknown. We
      have compared and contrasted the effects of high fat diet-induced obesity on
      glucose metabolism and leukocyte activation in multiple depots in male and female
      C57Bl/6 mice. With both short term and long term high fat diet, male mice
      demonstrated increased weight gain and CD11c(+) adipose tissue macrophage content
      compared with female mice despite similar degrees of adipocyte hypertrophy.
      Competitive bone marrow transplant studies demonstrated that obesity induced a
      preferential contribution of male hematopoietic cells to circulating leukocytes
      and adipose tissue macrophages compared with female cells independent of the sex
      of the recipient. Sex differences in macrophage and hematopoietic cell in vitro
      activation in response to obesogenic cues were observed to explain these results.
      In summary, this report demonstrates that male and female leukocytes and
      hematopoietic stem cells have cell-autonomous differences in their response to
      obesity that contribute to an amplified response in males compared with females. 

PMID- 25869129
TI  - Tricyclic Antidepressant Amitriptyline-induced Glial Cell Line-derived
      Neurotrophic Factor Production Involves Pertussis Toxin-sensitive Galphai/o
      Activation in Astroglial Cells.
AB  - Further elaborating the mechanism of antidepressants, beyond modulation of
      monoaminergic neurotransmission, this study sought to elucidate the mechanism of
      amitriptyline-induced production of glial cell line-derived neurotrophic factor
      (GDNF) in astroglial cells. Previous studies demonstrated that an amitriptyline
      evoked matrix metalloproteinase (MMP)/FGF receptor (FGFR)/FGFR substrate 2alpha
      (FRS2alpha)/ERK cascade is crucial for GDNF production, but how amitriptyline
      triggers this cascade remains unknown. MMP is activated by intracellular
      mediators such as G proteins, and this study sought to clarify the involvement of
      G protein signaling in amitriptyline-evoked GDNF production in rat C6 astroglial
      cells (C6 cells), primary cultured rat astrocytes, and normal human astrocytes.
      Amitriptyline-evoked GDNF mRNA expression and release were inhibited by pertussis
      toxin (PTX), a Galpha(i/o) inhibitor, but not by NF449, a Galpha(s) inhibitor, or
      YM-254890, a Galphaq inhibitor. The activation of the GDNF production cascade
      (FGFR/FRS2alpha/ERK) was also inhibited by PTX. Deletion of Galpha(omicron1) and
      Galpha(i3) by RNAi demonstrated that these G proteins play important roles in
      amitriptyline signaling. G protein activation was directly analyzed by electrical
      impedance-based biosensors (CellKey(TM) assay), using a label-free (without use
      of fluorescent proteins/probes or radioisotopes) and real time approach.
      Amitriptyline increased impedance, indicating Galpha(i/o) activation that was
      suppressed by PTX treatment. The impedance evoked by amitriptyline was not
      affected by inhibitors of the GDNF production cascade. Furthermore, FGF2
      treatment did not elicit any effect on impedance, indicating that amitriptyline
      targets PTX-sensitive Galpha(i/o) upstream of the MMP/FGFR/FRS2alpha/ERK cascade.
      These results suggest novel targeting for the development of antidepressants.

PMID- 25869130
TI  - Conformational Dynamics of DNA Repair by Escherichia coli Endonuclease III.
AB  - Escherichia coli endonuclease III (Endo III or Nth) is a DNA glycosylase with a
      broad substrate specificity for oxidized or reduced pyrimidine bases. Endo III
      possesses two types of activities: N-glycosylase (hydrolysis of the N-glycosidic
      bond) and AP lyase (elimination of the 3'-phosphate of the AP-site). We report a
      pre-steady-state kinetic analysis of structural rearrangements of the DNA
      substrates and uncleavable ligands during their interaction with Endo III.
      Oligonucleotide duplexes containing 5,6-dihydrouracil, a natural abasic site, its
      tetrahydrofuran analog, and undamaged duplexes carried fluorescent DNA base
      analogs 2-aminopurine and 1,3-diaza-2-oxophenoxazine as environment-sensitive
      reporter groups. The results suggest that Endo III induces several fast
      sequential conformational changes in DNA during binding, lesion recognition, and
      adjustment to a catalytically competent conformation. A comparison of two
      fluorophores allowed us to distinguish between the events occurring in the
      damaged and undamaged DNA strand. Combining our data with the available
      structures of Endo III, we conclude that this glycosylase uses a multistep
      mechanism of damage recognition, which likely involves Gln(41) and Leu(81) as DNA
      lesion sensors. 

PMID- 25869131
TI  - Negative Regulation of Leptin-induced Reactive Oxygen Species (ROS) Formation by
      Cannabinoid CB1 Receptor Activation in Hypothalamic Neurons.
AB  - The adipocyte-derived, anorectic hormone leptin was recently shown to owe part of
      its regulatory effects on appetite-regulating hypothalamic neuropeptides to the
      elevation of reactive oxygen species (ROS) levels in arcuate nucleus (ARC)
      neurons. Leptin is also known to exert a negative regulation on hypothalamic
      endocannabinoid levels and hence on cannabinoid CB1 receptor activity. Here we
      investigated the possibility of a negative regulation by CB1 receptors of leptin
      mediated ROS formation in the ARC. Through pharmacological and molecular biology
      experiments we report data showing that leptin-induced ROS accumulation is 1)
      blunted by arachidonyl-2'-chloroethylamide (ACEA) in a CB1-dependent manner in
      both the mouse hypothalamic cell line mHypoE-N41 and ARC neuron primary cultures,
      2) likewise blocked by a peroxisome proliferator-activated receptor-gamma (PPAR
      gamma) agonist, troglitazone, in a manner inhibited by T0070907, a PPAR-gamma
      antagonist that also inhibited the ACEA effect on leptin, 3) blunted under
      conditions of increased endocannabinoid tone due to either pharmacological or
      genetic inhibition of endocannabinoid degradation in mHypoE-N41 and primary ARC
      neuronal cultures from MAGL(-/-) mice, respectively, and 4) associated with
      reduction of both PPAR-gamma and catalase activity, which are reversed by both
      ACEA and troglitazone. We conclude that CB1 activation reverses leptin-induced
      ROS formation and hence possibly some of the ROS-mediated effects of the hormone
      by preventing PPAR-gamma inhibition by leptin, with subsequent increase of
      catalase activity. This mechanism might underlie in part CB1 orexigenic actions
      under physiopathological conditions accompanied by elevated hypothalamic
      endocannabinoid levels. 

PMID- 25869133
TI  - Autophagy modulates articular cartilage vesicle formation in primary articular
      chondrocytes.
AB  - Chondrocyte-derived extracellular organelles known as articular cartilage
      vesicles (ACVs) participate in non-classical protein secretion, intercellular
      communication, and pathologic calcification. Factors affecting ACV formation and
      release remain poorly characterized; although in some cell types, the generation
      of extracellular vesicles is associated with up-regulation of autophagy. We
      sought to determine the role of autophagy in ACV production by primary articular
      chondrocytes. Using an innovative dynamic model with a light scatter nanoparticle
      counting apparatus, we determined the effects of autophagy modulators on ACV
      number and content in conditioned medium from normal adult porcine and human
      osteoarthritic chondrocytes. Healthy articular chondrocytes release ACVs into
      conditioned medium and show significant levels of ongoing autophagy. Rapamycin,
      which promotes autophagy, increased ACV numbers in a dose- and time-dependent
      manner associated with increased levels of autophagy markers and autophagosome
      formation. These effects were suppressed by pharmacologic autophagy inhibitors
      and short interfering RNA for ATG5. Caspase-3 inhibition and a Rho/ROCK inhibitor
      prevented rapamycin-induced increases in ACV number. Osteoarthritic chondrocytes,
      which are deficient in autophagy, did not increase ACV number in response to
      rapamycin. SMER28, which induces autophagy via an mTOR-independent mechanism,
      also increased ACV number. ACVs induced under all conditions had similar ecto
      enzyme specific activities and types of RNA, and all ACVs contained LC3, an
      autophagosome-resident protein. These findings identify autophagy as a critical
      participant in ACV formation, and augment our understanding of ACVs in cartilage
      disease and repair. 

PMID- 25869132
TI  - Structural Basis for the Inverted Repeat Preferences of mariner Transposases.
AB  - The inverted repeat (IR) sequences delimiting the left and right ends of many
      naturally active mariner DNA transposons are non-identical and have different
      affinities for their transposase. We have compared the preferences of two active
      mariner transposases, Mos1 and Mboumar-9, for their imperfect transposon IRs in
      each step of transposition: DNA binding, DNA cleavage, and DNA strand transfer. A
      3.1 A resolution crystal structure of the Mos1 paired-end complex containing the
      pre-cleaved left IR sequences reveals the molecular basis for the reduced
      affinity of the Mos1 transposase DNA-binding domain for the left IR as compared
      with the right IR. For both Mos1 and Mboumar-9, in vitro DNA transposition is
      most efficient when the preferred IR sequence is present at both transposon ends.
      We find that this is due to the higher efficiency of cleavage and strand transfer
      of the preferred transposon end. We show that the efficiency of Mboumar-9
      transposition is improved almost 4-fold by changing the 3' base of the preferred
      Mboumar-9 IR from guanine to adenine. This preference for adenine at the reactive
      3' end for both Mos1 and Mboumar-9 may be a general feature of mariner
      transposition. 

PMID- 25869134
TI  - Zinc Binding to MG53 Protein Facilitates Repair of Injury to Cell Membranes.
AB  - Zinc is an essential trace element that participates in a wide range of
      biological functions, including wound healing. Although Zn(2+) deficiency has
      been linked to compromised wound healing and tissue repair in human diseases, the
      molecular mechanisms underlying Zn(2+)-mediated tissue repair remain unknown. Our
      previous studies established that MG53, a TRIM (tripartite motif) family protein,
      is an essential component of the cell membrane repair machinery. Domain homology
      analysis revealed that MG53 contains two Zn(2+)-binding motifs. Here, we show
      that Zn(2+) binding to MG53 is indispensable to assembly of the cell membrane
      repair machinery. Live cell imaging illustrated that Zn(2+) entry from
      extracellular space is essential for translocation of MG53-containing vesicles to
      the acute membrane injury sites for formation of a repair patch. The effect of
      Zn(2+) on membrane repair is abolished in mg53(-/-) muscle fibers, suggesting
      that MG53 functions as a potential target for Zn(2+) during membrane repair.
      Mutagenesis studies suggested that both RING and B-box motifs of MG53 constitute
      Zn(2+)-binding domains that contribute to MG53-mediated membrane repair. Overall,
      this study establishes a base for Zn(2+) interaction with MG53 in protection
      against injury to the cell membrane. 

PMID- 25869135
TI  - Biochemical Validation of the Glyoxylate Cycle in the Cyanobacterium
      Chlorogloeopsis fritschii Strain PCC 9212.
AB  - Cyanobacteria are important photoautotrophic bacteria with extensive but variable
      metabolic capacities. The existence of the glyoxylate cycle, a variant of the TCA
      cycle, is still poorly documented in cyanobacteria. Previous studies reported the
      activities of isocitrate lyase and malate synthase, the key enzymes of the
      glyoxylate cycle in some cyanobacteria, but other studies concluded that these
      enzymes are missing. In this study the genes encoding isocitrate lyase and malate
      synthase from Chlorogloeopsis fritschii PCC 9212 were identified, and the
      recombinant enzymes were biochemically characterized. Consistent with the
      presence of the enzymes of the glyoxylate cycle, C. fritschii could assimilate
      acetate under both light and dark growth conditions. Transcript abundances for
      isocitrate lyase and malate synthase increased, and C. fritschii grew faster,
      when the growth medium was supplemented with acetate. Adding acetate to the
      growth medium also increased the yield of poly-3-hydroxybutyrate. When the genes
      encoding isocitrate lyase and malate synthase were expressed in Synechococcus sp.
      PCC 7002, the acetate assimilation capacity of the resulting strain was greater
      than that of wild type. Database searches showed that the genes for the
      glyoxylate cycle exist in only a few other cyanobacteria, all of which are able
      to fix nitrogen. This study demonstrates that the glyoxylate cycle exists in a
      few cyanobacteria, and that this pathway plays an important role in the
      assimilation of acetate for growth in one of those organisms. The glyoxylate
      cycle might play a role in coordinating carbon and nitrogen metabolism under
      conditions of nitrogen fixation. 

PMID- 25869136
TI  - A salt bridge linking the first intracellular loop with the C terminus
      facilitates the folding of the serotonin transporter.
AB  - The folding trajectory of solute carrier 6 (SLC6) family members is of interest
      because point mutations result in misfolding and thus cause clinically relevant
      phenotypes in people. Here we examined the contribution of the C terminus in
      supporting folding of the serotonin transporter (SERT; SLC6A4). Our working
      hypothesis posited that the amphipathic nature of the C-terminal alpha-helix
      (Thr(603)-Thr(613)) was important for folding of SERT. Accordingly, we disrupted
      the hydrophobic moment of the alpha-helix by replacing Phe(604), Ile(608), or
      Ile(612) by Gln. The bulk of the resulting mutants SERT-F604Q, SERT-I608Q, and
      SERT-I612Q were retained in the endoplasmic reticulum, but their residual
      delivery to the cell surface still depended on SEC24C. This indicates that the
      amphipathic nature of the C-terminal alpha-helix was dispensable to endoplasmic
      reticulum export. The folding trajectory of SERT is thought to proceed through
      the inward facing conformation. Consistent with this conjecture, cell surface
      expression of the misfolded mutants was restored by (i) introducing second site
      suppressor mutations, which trap SERT in the inward facing state, or (ii) by the
      pharmacochaperone noribogaine, which binds to the inward facing conformation.
      Finally, mutation of Glu(615) at the end of the C-terminal alpha-helix to Lys
      reduced surface expression of SERT-E615K. A charge reversal mutation in
      intracellular loop 1 restored surface expression of SERT-R152E/E615K to wild type
      levels. These observations support a mechanistic model where the C-terminal
      amphipathic helix is stabilized by an intramolecular salt bridge between residues
      Glu(615) and Arg(152). This interaction acts as a pivot in the conformational
      search associated with folding of SERT. 

PMID- 25869137
TI  - An Accessory Agonist Binding Site Promotes Activation of alpha4beta2* Nicotinic
      Acetylcholine Receptors.
AB  - Neuronal nicotinic acetylcholine receptors containing alpha4, beta2, and
      sometimes other subunits (alpha4beta2* nAChRs) regulate addictive and other
      behavioral effects of nicotine. These nAChRs exist in several stoichiometries,
      typically with two high affinity acetylcholine (ACh) binding sites at the
      interface of alpha4 and beta2 subunits and a fifth accessory subunit. A third low
      affinity ACh binding site is formed when this accessory subunit is alpha4 but not
      if it is beta2. Agonists selective for the accessory ACh site, such as 3-[3-(3
      pyridyl)-1,2,4-oxadiazol-5-yl]benzonitrile (NS9283), cannot alone activate a
      nAChR but can facilitate more efficient activation in combination with agonists
      at the canonical alpha4beta2 sites. We therefore suggest categorizing agonists
      according to their site selectivity. NS9283 binds to the accessory ACh binding
      site; thus it is termed an accessory site-selective agonist. We expressed
      (alpha4beta2)2 concatamers in Xenopus oocytes with free accessory subunits to
      obtain defined nAChR stoichiometries and alpha4/accessory subunit interfaces. We
      show that alpha2, alpha3, alpha4, and alpha6 accessory subunits can form binding
      sites for ACh and NS9283 at interfaces with alpha4 subunits, but beta2 and beta4
      accessory subunits cannot. To permit selective blockage of the accessory site,
      alpha4 threonine 126 located on the minus side of alpha4 that contributes to the
      accessory site, but not the alpha4beta2 sites, was mutated to cysteine.
      Alkylation of this cysteine with a thioreactive reagent blocked activity of ACh
      and NS9283 at the accessory site. Accessory agonist binding sites are promising
      drug targets. 

PMID- 25869138
TI  - Spy1 Protein Mediates Phosphorylation and Degradation of SCG10 Protein in Axonal
      Degeneration.
AB  - Axon loss is a destructive consequence of a wide range of neurological diseases
      without a clearly defined mechanism. Recent data demonstrate that SCG10 is a
      novel axonal maintenance factor and that rapid SCG10 loss after injury requires
      JNK activity; how JNK induces degradation of SCG10 is not well known. Here we
      showed that SCG10 was a binding partner of Spy1, a Speedy/RINGO family protein,
      which participated in cellular response to sciatic nerve injury. During the early
      stage of axonal injury, Spy1 expression was inversely correlated with SCG10. Spy1
      mediated SCG10 phosphorylation and degradation partly in a JNK-dependent manner.
      Inhibition of Spy1 attenuated SCG10 phosphorylation and delayed injury-induced
      axonal degeneration. Taken together, these data suggest that Spy1 is an important
      regulator of SCG10 and can be targeted in future axo-protective therapeutics. 

PMID- 25869140
TI  - Spontaneous Rupture of an Intrasplenic Aneurysm After Pancreaticoduodenectomy for
      Pancreatic Ductal Adenocarcinoma.

PMID- 25869141
TI  - What's in Your Satchel? Things Best Not Forgotten: Reflections on a Year in Peru.

PMID- 25869139
TI  - Metabotropic Glutamate Receptors: MODULATORS OF CONTEXT-DEPENDENT FEEDING
      BEHAVIOUR IN C. ELEGANS.
AB  - Glutamatergic neurotransmission is evolutionarily conserved across animal phyla.
      A major class of glutamate receptors consists of the metabotropic glutamate
      receptors (mGluRs). In C. elegans, three mGluR genes, mgl-1, mgl-2, and mgl-3,
      are organized into three subgroups, similar to their mammalian counterparts.
      Cellular reporters identified expression of the mgls in the nervous system of C.
      elegans and overlapping expression in the pharyngeal microcircuit that controls
      pharyngeal muscle activity and feeding behavior. The overlapping expression of
      mgls within this circuit allowed the investigation of receptor signaling per se
      and in the context of receptor interactions within a neural network that
      regulates feeding. We utilized the pharmacological manipulation of neuronally
      regulated pumping of the pharyngeal muscle in the wild-type and mutants to
      investigate MGL function. This defined a net mgl-1-dependent inhibition of
      pharyngeal pumping that is modulated by mgl-3 excitation. Optogenetic activation
      of the pharyngeal glutamatergic inputs combined with electrophysiological
      recordings from the isolated pharyngeal preparations provided further evidence
      for a presynaptic mgl-1-dependent regulation of pharyngeal activity. Analysis of
      mgl-1, mgl-2, and mgl-3 mutant feeding behavior in the intact organism after
      acute food removal identified a significant role for mgl-1 in the regulation of
      an adaptive feeding response. Our data describe the molecular and cellular
      organization of mgl-1, mgl-2, and mgl-3. Pharmacological analysis identified
      that, in these paradigms, mgl-1 and mgl-3, but not mgl-2, can modulate the
      pharyngeal microcircuit. Behavioral analysis identified mgl-1 as a significant
      determinant of the glutamate-dependent modulation of feeding, further
      highlighting the significance of mGluRs in complex C. elegans behavior. 

PMID- 25869142
TI  - Editor's Introduction.

PMID- 25869143
TI  - Embracing the oneness of all things: a personal reflection on the implications of
      shamanism for social work practice in end-of-life and palliative care.

PMID- 25869144
TI  - Appreciating cultural dimensions and connections in hospice care.

PMID- 25869145
TI  - End-of-life care as a field of practice in the social work curriculum.
AB  - Attention to end-of-life care in social work education and practice is growing.
      With funding from the Project on Death in America, in 2001, the University of
      Iowa, School of Social Work developed and implemented an End-of-Life Field of
      Practice. Unlike a concentration, a Field of Practice is a set of integrated
      courses focused on one specific area of focus. This article describes the Field
      of Practice, the community-based partnerships, and the curriculum that serves as
      a basis for training the students enrolled in this area. Strategies for other
      social work programs interested in developing a similar Field of Practice or
      specialty area in their MSW curricula are provided. These include faculty
      committed to the content area, comprehensive course offerings to encompass all
      aspects of end-of-life care, and field sites willing to help train students. 

PMID- 25869146
TI  - Dying in the age of choice.
AB  - Due to the unprecedented increase in the United States aging demographics, many
      more people are living longer and reaching older ages than ever before. However,
      a longer life is not necessarily a better life, as the vast majority will face a
      period of prolonged deteriorating health prior to death. Although notable efforts
      have been underway that are designed to improve the end-of-life experience,
      increasing numbers of individuals express a desire and/or act upon an intent to
      end their lives precipitously. Though still limited, the options to actively
      participate in their own deaths are growing. Requests for a hastened death can
      occur among people of all ages and includes those with advanced illness as well
      as others wanting to die due to unbearable suffering. This article provides an
      overview of the ongoing discourse about the experience of dying faced by many
      older adults, including aspects frequently associated with "a good death." The
      limitations of established practices which seek to provide a "better" dying
      experience are identified followed by discussion of the growing availability of
      alternative options. Reflective considerations are presented to guide practice
      vis-a-vis the changing landscape surrounding options in dying. 

PMID- 25869147
TI  - "I was ready to take him home": next-of-kin's accounts of loved one's death
      during hospice and palliative care discussions in Veterans Affairs Medical
      Centers.
AB  - This study explored next-of-kin's retrospective accounts of hospice and
      palliative care discussions for hospitalized veterans. In-depth, face-to-face
      interviews were used to generate narrative accounts of 78 next-of-kin's
      experience of their loved one's hospital care during the last days of the
      patient's life. One-third of participants reported taking part in a hospice or
      palliative care discussion during the patient's final hospitalization. In over
      one-half of those cases, the patients died before discharge or transfer to
      hospice or palliative care was accomplished. Hospice and palliative care
      discussions in the hospital setting shaped family perceptions of the patients'
      care, directed family efforts in the days prior to death, and engendered
      anticipation of remaining quality time with the patient. Discussions about
      hospice or palliative care have meaning, emotional impact, practical effects, and
      unintended consequences for next-of-kin. Social workers in hospital settings can
      play a critical role in supporting family members through the hospice and
      palliative care discussion process and facilitate timely care transitions. They
      also can attend to the psychosocial concerns of family members, particularly when
      death occurs prior to discharge to hospice or transfer to an inpatient palliative
      care service. 

PMID- 25869148
TI  - Patterns in adult sibling relationships after the death of one or both parents.
AB  - The authors explored how sibling relationships were affected by the death of one
      or both parents in the context of the dynamics of those sibling relationships
      prior to the death. Qualitative data obtained from 66 interviews in a mixed
      methods study of adults in middle or older age with at least one living sibling
      were analyzed for the purpose of finding common patterns that emerged after the
      death. The patterns were: Even closer; Just us now; New roles, responsibilities,
      and relationships; Unsettled estate; Never close; From bad to worse; Back
      together, temporarily; and No change. Implications for social work practice
      include exploring perceptions of family members regarding patterns and using the
      concept of ambivalence to normalize sibling relationships. 

PMID- 25869149
TI  - Isotopocule analysis of biologically produced nitrous oxide in various
      environments.
AB  - Natural abundance ratios of isotopocules, molecules that have the same chemical
      constitution and configuration, but that only differ in isotope substitution,
      retain a record of a compound's origin and reactions. A method to measure
      isotopocule ratios of nitrous oxide (N2 O) has been established by using mass
      analysis of molecular ions and fragment ions. The method has been applied widely
      to environmental samples from the atmosphere, ocean, fresh water, soils, and
      laboratory-simulation experiments. Results show that isotopocule ratios,
      particularly the 15 N-site preference (difference between isotopocule ratios 14
      N15 N16 O/14 N14 N16 O and 15 N14 N16 O/14 N14 N16 O), have a wide range that
      depends on their production and consumption processes. Observational and
      laboratory studies of N2 O related to biological processes are reviewed and
      discussed to elucidate complex material cycles of this trace gas, which causes
      global warming and stratospheric ozone depletion. (c) 2015 Wiley Periodicals,
      Inc. Mass Spec Rev 36:135-160, 2017.

PMID- 25869150
TI  - WC Nanocrystals Grown on Vertically Aligned Carbon Nanotubes: An Efficient and
      Stable Electrocatalyst for Hydrogen Evolution Reaction.
AB  - Single nanocrystalline tungsten carbide (WC) was first synthesized on the tips of
      vertically aligned carbon nanotubes (VA-CNTs) with a hot filament chemical vapor
      deposition (HF-CVD) method through the directly reaction of tungsten metal with
      carbon source. The VA-CNTs with preservation of vertical structure integrity and
      alignment play an important role to support the nanocrystalline WC growth. With
      the high crystallinity, small size, and uniform distribution of WC particles on
      the carbon support, the formed WC-CNTs material exhibited an excellent catalytic
      activity for hydrogen evolution reaction (HER), giving a eta10 (the overpotential
      for driving a current of 10 mA cm(-2)) of 145 mV, onset potential of 15 mV,
      exchange current density@ 300 mV of 117.6 mV and Tafel slope values of 72 mV dec(
      1) in acid solution, and eta10 of 137 mV, onset potential of 16 mV, exchange
      current density@ 300 mV of 33.1 mV and Tafel slope values of 106 mV dec(-1) in
      alkaline media, respectively. Electrochemical stability test further confirms the
      long-term operation of the catalyst in both acidic and alkaline media. 

PMID- 25869151
TI  - Electrical stimulation therapy for the treatment of pressure ulcers in
      individuals with spinal cord injury: a systematic review and meta-analysis.
AB  - To conduct a systematic review and meta-analysis on the effects of electrical
      stimulation therapy (EST) on healing pressure ulcers in individuals with spinal
      cord injury (SCI). CINAHL, The Cochrane Library, PubMed, SCOPUS, EMBASE, Nursing
      & Allied Health and Dissertation & Theses databases were searched for relevant
      English language articles from the date of inception to 31 January 2014. Separate
      searches were conducted in Google Scholar and academic journals specialised in
      wound care. Two reviewers independently assessed study eligibility. Studies were
      included if EST was used to treat pressure ulcers in individuals with SCI. A
      total of 599 articles were screened, and 15 studies met the inclusion criteria. A
      meta-analysis with five studies demonstrated that EST significantly decreased the
      ulcer size by 1.32%/day [95% confidence interval (CI): 0.58-2.05, P < 0.001]
      compared to standard wound care (SWC) or sham EST. Another meta-analysis
      conducted with four studies showed that EST increased the risk of wound healing
      by 1.55 times compared with standard wound care or sham EST (95% CI: 1.12 to
      2.15, P < 0.0001). Because of the wide array of outcome measures across studies,
      a single meta-analysis could not be conducted. EST appears to be an effective
      adjunctive therapy to accelerate and increase pressure ulcer closure in
      individuals with SCI.

PMID- 25869152
TI  - [Explanation of risky sexual behaviors in men who have sex with men].
AB  - OBJECTIVE: To explore views about risky sexual behaviors and perceptions of HIV,
      and to propose interventions for preventing HIV infections in a group of men who
      have sex with men. METHODS: We performed a qualitative study in a sample of 13
      men who have sex with men, who were participating in an HIV-seronegative cohort,
      and who we contacted via saunas for the gay community in Barcelona (Spain). We
      performed in-depth semi-structured interviews, followed by content analysis.
      RESULTS: Risky sexual behaviors were associated with masculinity related to
      strong sexual needs, certain sexual exchange venues (such as saunas, private
      parties and clubs), drug use, and a desire to experiment with risk and one's own
      sexuality. HIV infection was perceived as a normalized disease, although becoming
      infected was still associated with shame and guilt. Proposed interventions
      included raising awareness of what it is like to live with HIV, generating
      greater social alarm, incorporating new technologies in prevention, and
      intensifying activity at gay venues. CONCLUSIONS: The concept of masculinity
      plays a fundamental role in sexual practices among men who have sex with men. We
      suggest renewed innovation in preventive programs and incorporating the
      perception of risk and HIV infection from a gender perspective.

PMID- 25869153
TI  - Productivity loss due to premature mortality caused by blood cancer: a study
      based on patients undergoing stem cell transplantation.
AB  - INTRODUCTION: Stem cell transplantation has been used for many years to treat
      haematological malignancies that could not be cured by other treatments. Despite
      this medical breakthrough, mortality rates remain high. Our purpose was to
      evaluate labour productivity losses associated with premature mortality due to
      blood cancer in recipients of stem cell transplantations. METHODS: We collected
      primary data from the clinical histories of blood cancer patients who had
      undergone stem cell transplantation between 2006 and 2011 in two Spanish
      hospitals. We carried out a descriptive analysis and calculated the years of
      potential life lost and years of potential productive life lost. Labour
      productivity losses due to premature mortality were estimated using the Human
      Capital method. An alternative approach, the Friction Cost method, was used as
      part of the sensitivity analysis. RESULTS: Our findings suggest that, in a
      population of 179 transplanted and deceased patients, males and people who die
      between the ages of 30 and 49 years generate higher labour productivity losses.
      The estimated loss amounts to over ?31.4 million using the Human Capital method
      (?480,152 using the Friction Cost method), which means an average of ?185,855 per
      death. The highest labour productivity losses are produced by leukaemia. However,
      lymphoma generates the highest loss per death. CONCLUSIONS: Further efforts are
      needed to reduce premature mortality in blood cancer patients undergoing
      transplantations and reduce economic losses.

PMID- 25869154
TI  - [Alcohol consumption trends among Spanish school-aged adolescents in the first
      decade of the 21(st) century].
AB  - OBJECTIVE: To determine trends in beer, wine, and liquor consumption among
      Spanish adolescents in 2002, 2006, and 2010, as well as drunkenness trends during
      the same period. METHOD: The study sample was composed of 23,169 adolescents aged
      15 to 18 years old: 7,103 in 2002, 10,443 in 2006 and 5,623 in 2010. In the three
      time points of the study, the data were representative of Spanish adolescent
      students. We used the alcohol consumption questionnaire designed by the
      international team of the Health Behavior in School-aged Children (HBSC) study.
      We estimated odds ratios and 95% confidence intervals through logistic
      regressions. RESULTS: The main results showed a decrease in frequent consumption
      of wine and liquor from 2002 to 2010. This decrease was maintained after
      controlling for the variability due to the participants' gender and age. However,
      an increasing trend was found in drunkenness episodes in the different cohorts of
      the adolescents under study. CONCLUSIONS: The results of this study are of
      particular importance in the analysis of the effects of the public health
      policies implemented during this time period. We also found changes in
      consumption patterns of the various alcoholic drinks, which may constitute key
      information in the design of new public health policies.

PMID- 25869155
TI  - [Technical efficiency of traditional hospitals and public enterprises in
      Andalusia (Spain)].
AB  - OBJECTIVE: To assess the technical efficiency of traditional public hospitals
      without their own legal identity and subject to administrative law, and that of
      public enterprise hospitals, with their own legal identities and partly governed
      by private law, all of them belonging to the taxypayer-funded health system of
      Andalusia during the period 2005 -2008. METHODS: The study included the 32
      publicly-owned hospitals in Andalusia during the period 2005-2008. The method
      consisted of two stages. In the first stage, the indices of technical efficiency
      of the hospitals were calculated using Data Envelopment Analysis, and the change
      in total factor productivity was estimated using the Malmquist index. The results
      were compared according to perceived quality, and a sensitivity analysis was
      conducted through an auxiliary model and bootstrapping. In the second stage, a
      bivariate analysis was performed between hospital efficiency and organization
      type. RESULTS: Public enterprises were more efficient than traditional hospitals
      (on average by over 10%) in each of the study years. Nevertheless, a process of
      convergence was observed between the two types of organizations because, while
      the efficiency of traditional hospitals increased slightly (by 0.50%) over the
      study period, the performance of public enterprises declined by over 2%.
      DISCUSSION: The possible reasons for the greater efficiency of public enterprises
      include their greater budgetary and employment flexibility. However, the
      convergence process observed points to a process of mutual learning that is not
      necessarily efficient.

PMID- 25869156
TI  - Dental Stem Cells in Pulp Regeneration: Near Future or Long Road Ahead?
AB  - Although regenerative endodontic procedures have yielded an impressive body of
      favorable outcomes, the treatment of necrotic immature permanent teeth in
      particular remains to be a challenge. Recent advances in dental stem cell (DSC)
      research have gained increasing insight in their regenerative potential and
      prospective use in the formation of viable dental tissues. Numerous studies have
      already reported successful dental pulp regeneration following application of
      dental pulp stem cells, stem cells from the apical papilla, or dental follicle
      precursor cells in different in vivo models. Next to responsive cells, dental
      tissue engineering also requires the support of an appropriate scaffold material,
      ranging from naturally occurring polymers to treated dentin matrix components.
      However, the routine use and banking of DSCs still holds some major challenges,
      such as culture-associated differences, patient-related variability, and the
      effects of culture medium additives. Only in-depth evaluation of these problems
      and the implementation of standardized models and protocols will effectively lead
      to better alternatives for patients who no longer benefit from current treatment
      protocols. 

PMID- 25869157
TI  - Effects of serotonin depletion on punishment processing in the orbitofrontal and
      anterior cingulate cortices of healthy women.
AB  - Diminished synthesis of the neurotransmitter serotonin (5-HT) has been linked to
      disrupted impulse control in aversive contexts. However, the neural correlates
      underlying a serotonergic modulation of female impulsivity remain unclear. The
      present study investigated punishment-induced inhibition in healthy young women.
      Eighteen healthy female subjects (aged 20-31) participated in a double-blinded,
      counterbalanced, placebo-controlled, within subjects, repeated measures study.
      They were assessed on two randomly assigned occasions that were controlled for
      menstrual cycle phase. In a randomized order, one day, acute tryptophan depletion
      (ATD) was used to reduce 5-HT synthesis in the brain. On the other day,
      participants received a tryptophan-balanced amino acid load (BAL) as a control
      condition. Three hours after administration of ATD/BAL, neural activity was
      recorded during a modified Go/No-Go task implementing reward or punishment
      processes using functional magnetic resonance imaging (fMRI). Neural activation
      during No-Go trials in punishment conditions after BAL versus ATD administration
      correlated positively with the magnitude of central 5-HT depletion in the ventral
      and subgenual anterior cingulate cortices (ACC). Furthermore, neural activation
      in the medial orbitofrontal cortex (mOFC) and the dorsal ACC correlated
      positively with trait impulsivity. The results indicate reduced neural
      sensitivity to punishment after short-term depletion of 5-HT in brain areas
      related to emotion regulation (subgenual ACC) increasing with depletion magnitude
      and in brain areas related to appraisal and expression of emotions (mOFC and
      dorsal ACC), increasing with trait impulsivity. This suggests a serotonergic
      modulation of neural circuits related to emotion regulation, impulsive behavior,
      and punishment processing in females. 

PMID- 25869159
TI  - The use of archival tissues, organs and pathology museums: "mortui vivos docent"
      (let the dead teach the living).

PMID- 25869158
TI  - Transcutaneous vagus nerve stimulation (tVNS) enhances response selection during
      action cascading processes.
AB  - The ever-changing environment we are living in requires us to apply different
      action control strategies in order to fulfill a task goal. Indeed, when
      confronted with multiple response options it is fundamental to prioritize and
      cascade different actions. So far, very little is known about the neuromodulation
      of action cascading. In this study we assessed the causal role of the gamma
      aminobutyric acid (GABA)-ergic and noradrenergic system in modulating the
      efficiency of action cascading by applying transcutaneous vagus nerve stimulation
      (tVNS), a new non-invasive and safe method to stimulate the vagus nerve and to
      increase GABA and norepinephrine concentrations in the brain. A single-blind,
      sham-controlled, between-group design was used to assess the effect of on-line
      (i.e., stimulation overlapping with the critical task) tVNS in healthy young
      volunteers (n=30)-on a stop-change paradigm. Results showed that active, as
      compared to sham stimulation, enhanced response selection functions during action
      cascading and led to faster responses when two actions were executed in
      succession. These findings provide evidence for the important role of the GABA
      ergic and noradrenergic system in modulating performance in action cascading. 

PMID- 25869160
TI  - Fatal asphyxial episodes in the very young: classification and diagnostic issues.
AB  - Infants and young children are exposed to a relatively limited range of
      circumstances that may result in accidental or inflicted asphyxial deaths. These
      usually involve situations that interfere with oxygen uptake by the blood, or
      that decrease the amount of circulating oxygen. Typically infants and toddlers
      asphyxiate in sleeping accidents where they smother when their external airways
      are covered, hang when clothing is caught on projections inside cots, or wedge
      when they slip between mattresses and walls. Overlaying may cause asphyxiation
      due to a combination of airway occlusion and mechanical asphyxia, as may
      inflicted asphyxia with a pillow. The diagnosis of asphyxiation in infancy is
      difficult as there are usually no positive findings at autopsy and so
      differentiating asphyxiation from sudden infant death syndrome (SIDS) based
      purely on the pathological features will usually not be possible. Similarly, the
      autopsy findings in inflicted and accidental suffocation will often be identical.
      Classifications of asphyxia are sometimes confusing as particular types of
      asphyxiating events may involve several processes and so it may not be possible
      to precisely compartmentalize a specific incident. For this reason asphyxial
      events have been classified as being due to: insufficient oxygen availability in
      the surrounding environment, critical reduction of oxygen transfer from the
      atmosphere to the blood, impairment of oxygen transport in the circulating blood,
      or compromise of cellular oxygen uptake. The range of possible findings at the
      death scene and autopsy are reviewed, and the likelihood of finding
      markers/indicators of asphyxia is discussed. The conclusion that asphyxiation has
      occurred often has to be made by integrating aspects of the history, scene, and
      autopsy, while recognizing that none of these are necessarily pathognomonic, and
      also by excluding other possibilities. However, even after full investigation a
      diagnosis of asphyxia may not be possible and a number of issues concerning
      possible lethal terminal mechanisms may remain unresolved. 

PMID- 25869161
TI  - Increasing amplification success of forensic DNA samples using multiple
      displacement amplification.
AB  - Multiple displacement amplification (MDA) is capable of amplifying nanogram
      template amounts of DNA with high accuracy to generate micrograms of
      representative product. Although MDA is able to amplify small template amounts
      (<100 pg), increased levels of preferential amplification and allelic dropout are
      observed. The use of molecular crowders (polyethylene glycol 400) can decrease
      the amplification bias and increase amplification success. We describe the use of
      standard and crowded MDA on low-concentration casework samples originating from
      blood, semen, saliva, hair, and trace DNA. While standard MDA produced no
      significant increases in STR genotyping success, the use of crowded MDA yielded
      an average increase of 15% in the number of alleles, with a significant decrease
      in the amplification bias, resulting in clearer, more-complete profiles from
      forensically relevant samples. 

PMID- 25869162
TI  - Limited post-mortem examination. An alternative and viable way to avoid full
      examination?
AB  - A complete post-mortem examination is required in most medicolegal investigation
      systems. Though uncommon, some jurisdictions allow limited post-mortem
      examination if it is adequate to fulfil the death inquiries. One such
      jurisdiction is the state of Queensland with the commencement of the new Coroners
      Act. It permits the Coroner to order limited post-mortem examination confined to
      a specific region or regions of the body based on the circumstances received from
      the investigating police.There is a paucity of literature comparing the
      completeness of limited post-mortem examination compared with complete
      examination. We aim to study whether limited post-mortem examination can
      partially replace complete examination in specific circumstances. Archival post
      mortem reports with history are obtained. Cases where obvious complete post
      mortem examination is required [e.g., sudden infant death syndrome (SIDS),
      homicide, medicolegal hospital cases, pregnancy deaths], decomposed and
      skeletonized cases are excluded from the study. The region or regions (head,
      neck, chest, or abdomen) most appropriate for examination are derived from
      studying the circumstances given.Three hundred and fifty-one cases were reviewed,
      of which 136 were found to be suitable to be incorporated into the study.
      Discrepancies were present in 17.7% (n = 24) of the cases (15 cases due to
      different cause of death, seven due to changes in interpretation, and two where
      pathology may be significant to the family). When classified according to mode of
      death, the percentages were 46.4%, 11.1%, and 9.3% for the accident, natural, and
      suicide groups, respectively. When compared to region examined, the discrepancies
      were 9 out of 18 for head, 1 out of 20 for neck, 5 out of 70 for chest, none of
      out 2 for extremities, and 3 out of 4 for abdomen.The study showed a
      significantly high percentage of discrepancies when limited post-mortem
      examination was performed. The missed information may impede medicolegal
      inquiries, police investigation, and interfere with the course of justice.
      Significant information about familial disease may be missed. 

PMID- 25869163
TI  - A preliminary investigation into the scavenging activity on pig carcasses in
      Western Australia.
AB  - Human remains exposed to an outdoor environment are subject not only to the
      process of decomposition, but also to the activity of scavenging fauna. The
      scavenging behavior of fauna can vary considerably with region and season,
      affecting the rate of decomposition, and more importantly, the accuracy of
      postmortem interval estimations. A thorough knowledge of the scavenging behavior
      of fauna present in the local environment is imperative for law enforcement and
      forensic investigators dealing with decomposed remains located outdoors. This
      study was conducted to identify the major scavengers of decomposing remains in
      the southwest region of Western Australia. Avian species were identified as the
      dominant scavengers amongst a range of birds, reptiles, mammals, and amphibians
      feeding on cadaveric tissues and associated insects. The scavenging behavior of
      the fauna varied with seasonal factors, including temperature and rainfall. The
      preliminary results are useful for forensic investigations involving decomposed
      remains in the southwest region of Western Australia. 

PMID- 25869164
TI  - STRs vs. SNPs: thoughts on the future of forensic DNA testing.
AB  - Largely due to technological progress coming from the Human Genome and
      International HapMap Projects, the issue has been raised in recent years within
      the forensic DNA typing community of the potential for single nucleotide
      polymorphism (SNP) markers as possible replacements of the currently used short
      tandem repeat (STR) loci. Our human identity testing project team at the U.S.
      National Institute of Standards and Technology (NIST) has explored numerous SNP
      and STR loci and assays as well as developing miniSTRs for degraded DNA samples.
      Based on their power of discrimination, use in deciphering mixture components,
      and ability to be combined in multiplex assays in order to recover information
      from low amounts of biological material, we believe that STRs rather than SNPs
      will fulfill the dominant role in human identity testing for the foreseeable
      future. However, SNPs may play a useful role in specialized applications such as
      mitochondrial DNA (mtDNA) testing, Y-SNPs as lineage markers, ancestry
      informative markers (AIMs), the prediction of phenotypic traits, and other
      potential niche forensic casework applications. 

PMID- 25869165
TI  - Vascular rupture-a rare lethal complication of neurofibromatosis v.
      Recklinghausen.
AB  - Neurofibromatosis type 1 (NF-1), a phacomatosis with an incidence of 1:3,000
      4,000, is characterized by multiple benign nerve tumors, skin cafe-au-lait spots
      and a variety of other dysplastic abnormalities, e.g., of blood vessels. On rare
      occasions NF-1 is associated with arterial dysplasia (vascular neurofibrosis),
      which is poorly defined and can result, e.g., in stenosis, rupture, arterio
      venous fistula, or the formation of aneurysms. Although a rare feature of
      neurofibromatosis, haemorrhage, e.g., after minimal trauma, is a potentially
      lethal complication of this disease. We report the case of a 40-year-old woman
      with a history of NF-1 who collapsed gasping for air and died subsequently.
      Autopsy revealed a massive cervicomediastinal haematoma with compression of the
      neck region due to a vessel rupture without an adequate trauma. This fatality
      demonstrates that, in rare cases of NF-1 patients, the possibility of internal
      haemorrhage due to vessel rupture being the cause of death should be taken into
      consideration in medicolegal investigations even as a spontaneous event in the
      absence of an adequate blunt trauma. 

PMID- 25869166
TI  - Writing impressions revealed by scanners.
AB  - Heavily impressed writing impressions in paper and impressions in glossy
      brochures are often difficult or impossible to develop using the electrostatic
      detection apparatus (ESDA, manufactured by Foster and Freeman). Oblique and
      specular reflectance lighting can be used but they are time-consuming techniques
      and not always very successful. This paper briefly describes a scanning and image
      processing method for producing excellent images of such writing impressions. 

PMID- 25869167
TI  - Traumatic intercostal artery pseudoaneurysm following a bicycle accident.
AB  - In this article we present a fatal case of a ruptured intercostal artery
      pseudoaneurysm that occurred a number of years after an incident in which the
      patient suffered a blunt-trauma injury. A long interval between blunt trauma and
      this type of fatality has rarely been reported. This case discusses a 49-year-old
      woman who was found dead at her home by her husband and was referred for autopsy
      because the cause of death was uncertain. Her past medical history was unknown;
      however, it was learned that she had a bicycle accident 4 years previously and
      had sustained injuries to the left side of her body. During the autopsy, healed
      fractures in the bones of the left lower rib cage and a large amount of blood in
      the left thorax were observed. Furthermore, a hematoma, containing a small
      rupture was found in the left tenth intercostal space adjacent to the thoracic
      vertebrae. Histological examinations showed that the wall of the left tenth
      intercostal artery was ruptured, with recent blood clots including fibrin.
      Additionally, in the lesion where the tunica adventitia was disrupted, the
      dissecting cavity was filled with blood. We concluded that the woman died of
      hemorrhagic shock resulting from a ruptured intercostal artery pseudoaneurysm
      that formed as a result of the injury incurred from the bicycle accident 4 years
      before. 

PMID- 25869168
TI  - DNA reviews: Ancient DNA.
AB  - The rapid development, success, and occasional failures of forensic DNA profiling
      are highly publicised, and as a consequence are well known to the scientific and
      public communities alike. Over the same period of time that forensic DNA typing
      has accelerated onto the scene, another related discipline has been born and has
      made equally, or perhaps, even more groundbreaking achievements in the same
      arena; that is the science of (bio)molecular archaeology. This review describes
      the extreme complications of ancient DNA analysis and highlights some of the
      major achievements that have been accomplished in this field. The nature of DNA
      degradation and possible solutions to this problem are discussed. 

PMID- 25869169
TI  - Current status of routine post-mortem CT in Melbourne, Australia.
AB  - In May 2005, a multidetector computed tomography (CT) scanner was installed into
      the mortuary of the Victorian Institute of Forensic Medicine (VIFM). Since that
      time most biological material admitted to the institute has been scanned. This
      article provides an overview of the experience gained and difficulties
      encountered by participants in this project. Discussion is presented on the
      incorporation of routine CT imaging into autopsy procedures, application of CT in
      forensic research, and how we believe the use of cross-sectional imaging will
      evolve in forensic investigation of the deceased. 

PMID- 25869170
TI  - Baalat 6.

PMID- 25869171
TI  - Rotem and transfusion protocols: not yet time to give recommendations.

PMID- 25869172
TI  - Transpulmonary pressure can be determined without esophageal pressure
      measurements.

PMID- 25869173
TI  - Buffered crystalloids and acid-base state: still searching the optimal balance?

PMID- 25869174
TI  - One-pot synthesis of M (M = Ag, Au)@SiO2 yolk-shell structures via an
      organosilane-assisted method: preparation, formation mechanism and application in
      heterogeneous catalysis.
AB  - We demonstrate the fabrication of yolk-shell catalysts consisting of a single M
      (M = Ag, Au) nanoparticle encapsulated within a hollow mesoporous organosilica
      shell via an organosilane-assisted strategy. The advantages of our method lie in
      its good controllability of the void space as well as the thickness of the
      mesoporous shell. The M@CTAB/SiO2 synthesized through a modified Stober method
      can transform to yolk-shell structures after adding (3
      aminopropyl)trimethoxysilane (APTMS)/TEOS or (3-aminopropyl)triethoxysilane
      (APTES)/TEOS into the synthetic medium. We give unambiguous evidence that the
      middle CTAB/SiO2 layer transforms into a less dense APTMS-rich organic-inorganic
      layer which was selectively removed in alkaline aqueous solution, while the amino
      functionalized hybrid shells remain intact. Moreover, we discuss the role of
      alkylamino groups in the shell in the transformation from Ag@SiO2 nanorattles to
      hollow structures when impregnating the as-synthesized Ag@SiO2 nanorattles in
      HAuCl4 aqueous solution. The nanorattles also exhibit high catalytic activity for
      the catalytic reduction of p-nitrophenol. 

PMID- 25869175
TI  - Whose clock makes yours tick? How maternal cardiorespiratory physiology
      influences newborns' heart rate variability.
AB  - This study examined the existence of direct maternal-infant physiological
      relatedness in respiratory sinus arrhythmia (RSA) when the infant was age 1, 2,
      4, 8, and 12 weeks. We instructed mothers to breathe at 6, 12, 15, 20, and 6
      cycles per minute while their infants lay on their body. The mother-infant ECG
      and respiration were registered and video recordings were made. RR-interval
      (RRI), respiration rate (fR) and RSA were calculated and mother-infant RSA
      response-patterns were analyzed. The results revealed that infants adjusted their
      RSA levels to their mothers' levels during the first 2 months of life, but not at
      3 months of age, which could be interpreted as a continuing intra-uterine effect.
      The attenuation between 2 and 3 months could be a reflection of the 2-month
      developmental shift of social orientation. 

PMID- 25869176
TI  - [Larger heads compensate for an increased risk of THA dislocation in high-risk
      patients].
AB  - BACKGROUND: Dislocation is a devastating complication after total hip
      arthroplasty (THA) and occurs in 2-5% of primary THA cases and 5-10% of revision
      THA cases. Assuming correct implantation, dislocation risk can be reduced
      primarily by capsular repair and the use of larger prosthetic heads. However,
      larger heads are also associated with risks like accelerated wear or implant
      loosening, which is why heads with a maximum diameter of 36 mm are currently
      standard in primary THA. In cases with high dislocation risk, the use of 40 mm
      and 44 mm heads should be considered. OBJECTIVES: This study aimed to quantify
      THA dislocation risk and retrospectively analyze the course of disease in high
      risk patients treated with 40 mm or 44 mm femoral heads after primary or revision
      THA, concerning dislocation and other complications suffered. MATERIALS AND
      METHODS: All patients with increased THA dislocation risk, treated from 2009
      2014, were evaluated regarding dislocations. The cases with installation of 40 mm
      or 44 mm prosthetic heads were classified using a self-developed 5-level risk
      score and retrospectively analyzed. RESULTS: During the observation period, 288
      THA interventions with increased dislocation risk were performed. In 278 cases
      with ball diameters <= 36 mm the dislocation rate was 15.1% (n=42). In 10 high
      dislocation-risk cases (3A to 4B according to recommended scoring system), 40 mm
      and 44 mm heads were used. After a 22.8 month mean follow-up, no THA dislocations
      were reported. CONCLUSION: Our results with 40 and 44 mm heads and the existing
      literature confirm much higher joint stability and, thus, significantly reduced
      dislocation risk with larger prosthetic heads in THA. Their use is, therefore,
      justified in high-risk patients and should be considered in future THA.

PMID- 25869177
TI  - [Prosthetic reconstruction in high amputations of the upper extremity].
AB  - BACKGROUND: Conventional upper arm prostheses are controlled via two surface
      electrodes that measure motor activity of two separately innervated muscle
      groups. The various prosthetic joints are chosen by co-contractions and
      controlled linearly by these two muscles. A harmonious and natural course of
      movements is not possible in this way. OBJECTIVES: Overview regarding surgical,
      therapeutical and prosthetic options in high amputations of the upper extremity.
      METHODS: Selective literature research including the authors' own experience in
      everyday clinical practice as well as a review of medical records. RESULTS:
      Selective nerve transfers of the amputated nerves of the brachial plexus to the
      remaining stump muscles can create up to six myosignals for intuitive and
      simultaneous control of the different prosthetic joints. In this way, an
      efficient and harmonious control of the prosthetic device is possible without the
      need to change between the different control levels. At the same time, possible
      neuromas are treated and painless wear of the prosthesis is achieved. Due to the
      resulting extended use of the prosthetic device, the demands regarding stump
      quality are increased. Thus, both surgically and by the means of the orthopedic
      technician a stable stump-socket connection should be achieved to enable optimal
      prosthetic function.

PMID- 25869178
TI  - Functional preservation of hippocampal CA1 by low-dose GYKI-52466 preconditioning
      in a rat model of hypoxic-ischemic brain injury.
AB  - Global ischemia during cardiac surgery, brain surgery and stroke leads to lasting
      neuropsychological impairments. Previously we showed that low-dose GYKI-52466
      preconditioning protects against kainic acid-induced seizures and unilateral
      hypoxic-ischemic (HI) damage in rats. Here, we evaluated low-dose GYKI-52466 on
      electrophysiological indices of hippocampal CA1 function after HI. Male Sprague
      Dawley rats (26 days old) were administered saline or GYKI-52466 (3mg/kg, s.c.)
      90 min before left common carotid artery occlusion and allowed to recover 2h
      prior to placement in a hypoxia chamber (1h; 8% O2/92% N2). On days 14 and 90
      post-HI, contralateral and, where possible, ipsilateral hippocampal slices were
      prepared and population spikes and field excitatory postsynaptic potentials
      (EPSPs) recorded at 30-32  degrees C. Slices with population spikes >= 3 mV
      and/or field EPSPs >= 1 mV were accepted for long-term potentiation (LTP) and
      depression (LTD) studies. GYKI-52466 preconditioning prevented the stroke-induced
      suppression of population spikes and field EPSPs in both contralateral and
      ipsilateral hippocampi at 14 and 90 days. On days 14 and 90, both LTP and LTD
      were readily induced in both contralateral and ipsilateral hippocampi from sham
      operated controls. After stroke, LTP was significantly impaired in contralateral
      and completely absent in ipsilateral hippocampi. In ischemic animals
      preconditioned with low-dose GYKI-52466, LTP was readily induced on both sides.
      Hippocampal LTD was unaffected by either HI or GYKI preconditioning on both days
      14 and 90. The present results indicate that prophylactic low-dose GYKI-52466
      preserves CA1 function and synaptic plasticity processes contralateral, and more
      importantly, ipsilateral to the site of damage.

PMID- 25869179
TI  - High resolution MR eye protocol optimization: Comparison between 3D-CISS, 3D-PSIF
      and 3D-VIBE sequences.
AB  - PURPOSE: The purpose of this study was to compare selected MRI pulse sequences
      and to evaluate their utility for depicting specific anatomic regions in the eye.
      METHODS: A High-Resolution (HR) 0.08 * 0.08 * 0.60 mm(3) MRI protocol was
      developed on a 1.5-T clinical system and applied in the left eye of an albino
      rabbit, utilizing a small field of view surface coil. The comprehensive MRI
      protocol consisted of two 3D (T2/T1)w sequences (3D-PSIF and 3D-CISS), and one 3D
      T1w sequence (3D-VIBE). The T1w 3D-VIBE sequence was acquired, before and after
      intravenous injection of 0.2 mmol/kgr gadolinium-DTPA. Signal-to-Noise Ratios
      (SNR) and Contrast-to-Noise Ratios (CNR) amongst specific eye anatomical areas
      were calculated for each sequence. The presence of artifacts was rated
      subjectively utilizing a 5 point scale. RESULTS: 3D-PSIF and 3D-CISS provide
      better delineation and visualization of the eye as compared with 3D-VIBE
      sequences. 3D-CISS images present the highest SNR and revealed better
      discrimination of the ocular surrounding tissues; its basic drawback though is
      related to ghost artifacts appearing in the anterior chamber and resulting in the
      lowest image quality. In post-contrast imaging, the T1w 3D-VIBE sequence provided
      the best overall image quality. Moreover, 3D (T2/T1)w sequences can provide good
      anatomic depiction of the eye segments. Agreement between the two independent
      readers was good. CONCLUSIONS: Optimization of a comprehensive MR eye imaging
      protocol is achieved. A higher SNR, a better spatial resolution and a reduction
      of the total scan time were obtained, thus making clinical MRI systems more
      reliable in eye imaging.

PMID- 25869180
TI  - Habitual dietary intake of beta-carotene, vitamin C, folate, or vitamin E may
      interact with single nucleotide polymorphisms on brachial-ankle pulse wave
      velocity in healthy adults.
AB  - PURPOSE: The interaction between genetics and diet may explain the present
      disagreement in the protective role of vitamin intake on cardiovascular disease.
      We cross-sectionally assessed the interaction of habitual dietary intake of beta
      carotene, vitamin C, folate, and vitamin E with single nucleotide polymorphisms
      (SNPs) on brachial-ankle pulse wave velocity (baPWV), a measure of arterial
      stiffness. METHODS: Dietary intakes of beta-carotene, vitamin C, folate, and
      vitamin E were quantified by a food frequency questionnaire in 3198 healthy men
      and women (>= 40 years) from the Korea Multi-Rural communities Cohort study.
      baPWV was measured, and 19 SNPs were genotyped. The associations and interactions
      between dietary vitamin intake, SNP genotype, and baPWV were assessed using
      general linear models. RESULTS: In both men and women, dietary intake of beta
      carotene, vitamin C, folate, or vitamin E and baPWV were not directly associated.
      Vitamin C, folate, and vitamin E intake had an interaction with rs4961 (ADD1)
      genotype on baPWV in men. rs4961 also interacted with folate intake on baPWV in
      women. In women, rs10817542 (ZNF618) and rs719856 (CD2AP) had an interaction with
      beta-carotene and folate intake and rs5443 (GNB3) had an interaction with vitamin
      E intake on baPWV. In general, minor allele homozygotes with low vitamin intake
      had higher baPWV than other subgroups. Results were similar when supplement users
      were excluded. CONCLUSIONS: Higher intake of dietary vitamin C, folate, and
      vitamin E may be related to high baPWV in healthy Korean men who are minor allele
      homozygotes of rs4961. In healthy Korean women, dietary folate, beta-carotene,
      and vitamin E intake may affect baPWV differently according to rs4961,
      rs10817542, rs719856, or rs5443 genotype. Greater dietary intake of these
      nutrients may protect those that are genetically vulnerable to stiffening of the
      arteries.

PMID- 25869181
TI  - Prevalence of thinness among children and adolescents in Shandong, China.
AB  - PURPOSE: Thinness in children and adolescents poses a considerable public health
      problem globally, especially in developing countries. The present study examined
      the prevalence of thinness among children and adolescents in Shandong, China.
      METHODS: Data for this study were obtained from a large cross-sectional survey of
      schoolchildren. A total of 42,348 students (21,248 boys and 21,100 girls) aged 7
      18 years participated in this study. Stature and weight of all subjects were
      measured; body mass index (BMI) was calculated from their stature and weight.
      International BMI cutoffs were used to define thinness. RESULTS: The overall
      prevalences of thinness grade 1, grade 2 and grade 3 among children and
      adolescents aged 7-18 years were 7.74, 1.43 and 0.61 % for boys and 11.51, 2.54
      and 1.03 % for girls, respectively; these figures were all significantly higher
      in girls than in boys (P < 0.01). Thin children and adolescents had lower stature
      levels than their counterparts in not thin group in all age groups (7-18 years).
      CONCLUSION: The prevalence of childhood thinness is still wide in Shandong
      Province, and public health and nutritional strategies must give attention to the
      intervention for thinness, including periodic monitoring, education on pattern of
      nutrition and healthy dietary behavior.

PMID- 25869182
TI  - Preface to the Special Issue on brain lipids.

PMID- 25869184
TI  - Trajectories of psychopathology and risky behaviors associated with childhood
      abuse and neglect in low-income urban African American girls.
AB  - The current study examined patterns of psychopathology, drug and alcohol use, and
      sexual behavior associated with childhood abuse and neglect in a high-risk sample
      of low-income African American girls seeking mental health treatment.
      Participants (N=177) were African American girls recruited from mental health
      clinics serving low-income communities in Chicago, IL and followed over six waves
      of data collection (T1-T6) reflecting early (mean age 14) to late (mean age 17)
      adolescence. Child abuse and neglect history was determined from adolescent and
      caregiver reports. Latent curve modeling examined patterns of internalizing and
      externalizing psychopathology, drug and alcohol use, sexual experience, and risky
      sexual behavior reported by girls and associations with reported child abuse and
      neglect. Overall, these trajectories indicated a decrease in internalizing and
      externalizing symptoms, stability of drug and alcohol use, and an increase in
      sexual experience and risky sexual behaviors over time. Child abuse and neglect
      was associated with increased internalizing symptoms and sexual experience at
      baseline and with externalizing symptoms and risky sexual behavior both at
      baseline and the final point. Child abuse and neglect was not significantly
      associated with alcohol or drug use. This study adds to the literature on the
      long-term consequences of child abuse and neglect by demonstrating patterns of
      psychopathology and risky behavior that persist over time in a high-risk group of
      girls with self or parent reported histories of abuse and neglect. Interventions
      that address externalizing problems and health risk behaviors may be of
      particular importance for this population. 

PMID- 25869185
TI  - Children neglected: Where cumulative risk theory fails.
AB  - Neglected children, by far the majority of children maltreated, experience an
      environment most deficient in cognitive stimulation and language exchange. When
      physical abuse co-occurs with neglect, there is more stimulation through negative
      parent-child interaction, which may lead to better cognitive outcomes, contrary
      to Cumulative Risk Theory. The purpose of the current study was to assess whether
      children only neglected perform worse on cognitive tasks than children neglected
      and physically abused. Utilizing LONGSCAN archived data, 271 children only
      neglected and 101 children neglected and physically abused in the first four
      years of life were compared. The two groups were assessed at age 6 on the WPPSI-R
      vocabulary and block design subtests, correlates of cognitive intelligence.
      Regression analyses were performed, controlling for additional predictors of poor
      cognitive outcome, including socioeconomic variables and caregiver depression.
      Children only neglected scored significantly worse than children neglected and
      abused on the WPPSI-R vocabulary subtest (p=0.03). The groups did not differ on
      the block design subtest (p=0.4). This study shows that for neglected children,
      additional abuse may not additively accumulate risk when considering intelligence
      outcomes. Children experiencing only neglect may need to be referred for services
      that address cognitive development, with emphasis on the linguistic environment,
      in order to best support the developmental challenges of neglected children. 

PMID- 25869186
TI  - Inter-country exploration of factors associated with admission to long-term
      institutional dementia care: evidence from the RightTimePlaceCare study.
AB  - AIM: To explore inter-country variation of factors associated with
      institutionalization of people with dementia. BACKGROUND: There is an urgent need
      for evidence on whether factors associated with admission to institutional
      dementia care are applicable across healthcare systems, as increasing evidence
      suggests that these factors could be country-specific. DESIGN: A prospective
      cohort study. METHOD: Primary data were collected in eight European countries, at
      baseline and after 3 months follow-up (November 2010-April 2012). The sample
      included 2014 dyads of people with dementia and their informal caregivers; 791
      patients were recently institutionalized, 1223 patients lived at home and were at
      risk of institutionalization. Associations between care setting (institution vs.
      home) and factors shown to influence institutionalization (e.g. cognition,
      independence in activities of daily life, behaviour) were studied. RESULTS:
      Considerable differences were found between the eight countries in
      characteristics of people with dementia who had been recently admitted to ILTC.
      However, caregiver burden appeared the most consistent factor associated with
      institutionalization in all analyses. Indications for the importance of
      independence in activities of daily life were found as well, although country
      differences may be more prominent for this factor. CONCLUSION: Evidence was found
      for two common factors, crucial in the process of institutionalization across
      countries: caregiver burden and independency in activities of daily life.
      However, this study also suggests that admission to institutional dementia care
      is context-specific, as wide variation exists in factors associated with
      institutionalization across countries. Tailored best-practice strategies are
      needed to reflect variations in response to these needs.

PMID- 25869187
TI  - Effects of occupational exposure to polychlorinated biphenyls on urinary
      metabolites of neurotransmitters: A cross-sectional and longitudinal perspective.
AB  - BACKGROUND: Polychlorinated biphenyls (PCBs) are chemicals which were used for
      industrial purposes and are known to induce various adverse health effects. They
      are also known to be neurotoxic and numerous targets within the central nervous
      system have been identified in previous studies. Specifically, the
      neurotransmitters dopamine (DA) and norepinephrine (NE) are influenced by PCBs as
      indicated in studies involving animals. However, limited evidence has been
      published documenting PCB induced changes in the neurotransmitter system in
      humans. OBJECTIVE: In the present study, we examined the association between a
      higher PCB body burden following occupational exposure and possible changes in
      human neurotransmitter metabolites. METHODS: Within a medical surveillance
      programme called HELPcB (Health Effects in High-Level Exposure to PCB) that
      monitors adverse health effects of occupational PCB exposure, urine samples were
      obtained (n(T1) = 166; n(T2) = 177 and n(T3) = 141). The urinary concentrations
      of the metabolites homovanillic acid (HVA; for DA) and vanillylmandelic acid
      (VMA; for NE) were analyzed. Blood samples were obtained by vena puncture in
      order to determine the internal exposure to PCBs with human biomonitoring.
      RESULTS: A cross-sectional analysis indicated a significant negative effect of
      PCB exposure on HVA and VMA. Longitudinally, an initially higher exposure to
      higher chlorinated PCBs was followed by constant reduced HVA level over three
      consecutive years. Exploratory analyses show different long-term effects for
      different PCBs according to their chlorination degree. A higher exposure with
      lower chlorinated PCBs leads to an increase of VMA and HVA. Conversely, a higher
      exposure to all PCBs results in a reduction of HVA. CONCLUSION: This study, to
      our knowledge, is the first to document changes in neurotransmitter metabolites
      after occupational PCB exposure in humans. This finding advances evidence
      obtained from past research, and identifies one potential pathomechanism in the
      central dopaminergic system of humans.

PMID- 25869189
TI  - Response letter to "Can't we all just get along?".

PMID- 25869188
TI  - Cerebellar Premotor Output Neurons Collateralize to Innervate the Cerebellar
      Cortex.
AB  - Motor commands computed by the cerebellum are hypothesized to use corollary
      discharge, or copies of outgoing commands, to accelerate motor corrections.
      Identifying sources of corollary discharge, therefore, is critical for testing
      this hypothesis. Here we verified that the pathway from the cerebellar nuclei to
      the cerebellar cortex in mice includes collaterals of cerebellar premotor output
      neurons, mapped this collateral pathway, and identified its postsynaptic targets.
      Following bidirectional tracer injections into a distal target of the cerebellar
      nuclei, the ventrolateral thalamus, we observed retrogradely labeled somata in
      the cerebellar nuclei and mossy fiber terminals in the cerebellar granule layer,
      consistent with collateral branching. Corroborating these observations,
      bidirectional tracer injections into the cerebellar cortex retrogradely labeled
      somata in the cerebellar nuclei and boutons in the ventrolateral thalamus. To
      test whether nuclear output neurons projecting to the red nucleus also
      collateralize to the cerebellar cortex, we used a Cre-dependent viral approach,
      avoiding potential confounds of direct red nucleus-to-cerebellum projections.
      Injections of a Cre-dependent GFP-expressing virus into Ntsr1-Cre mice, which
      express Cre selectively in the cerebellar nuclei, retrogradely labeled somata in
      the interposed nucleus, and putative collateral branches terminating as mossy
      fibers in the cerebellar cortex. Postsynaptic targets of all labeled mossy fiber
      terminals were identified using immunohistochemical Golgi cell markers and
      electron microscopic profiles of granule cells, indicating that the collaterals
      of nuclear output neurons contact both Golgi and granule cells. These results
      clarify the organization of a subset of nucleocortical projections that
      constitute an experimentally accessible corollary discharge pathway within the
      cerebellum.

PMID- 25869190
TI  - Use of domperidone to increase breast milk supply: further consideration of the
      benefit-risk ratio is required.

PMID- 25869191
TI  - Response to "Use of domperidone to increase breast milk supply: further
      consideration of the benefit-risk ratio is required".

PMID- 25869192
TI  - Letter to the editor regarding "Does postoperative wound massage improve outcome
      of frenulotomy for breastfeeding difficulties in infants?".

PMID- 25869193
TI  - Breastfeeding was going well and now my nipples hurt: could my baby or I have a
      yeast infection?

PMID- 25869197
TI  - Is the coast clear for stent angioplasty of coarctation?

PMID- 25869198
TI  - Intermediate Outcomes in the Prospective, Multicenter Coarctation of the Aorta
      Stent Trial (COAST).
AB  - BACKGROUND: The Coarctation of the Aorta Stent Trial (COAST) was designed to
      assess the safety and efficacy of the Cheatham Platinum stent when used in
      children and adults with native or recurrent coarctation. Acute outcomes have
      been reported. We report here follow-up to 2 years. METHODS AND RESULTS: A total
      of 105 patients underwent attempted implantation, with 104 successes. There were
      no procedural deaths, serious adverse events, or surgical intervention. All
      patients experienced immediate reduction in upper- to lower-extremity blood
      pressure difference with sustained improvement to 2 years. Rates of hypertension
      and medication use decreased from baseline to 12 months and remained largely
      unchanged at 2 years. Six aortic aneurysms have been identified: 5 were
      successfully treated with covered stent placement, and 1 resolved without
      intervention. Stent fractures were noted in 2 patients at 1 year and 11 patients
      at 2 years, with evidence of fracture progression. To date, only larger stent
      diameter was associated with stent fracture. Twelve additional fractures have
      occurred after 2 years. No fracture has resulted in loss of stent integrity,
      stent embolization, aortic wall injury, or reobstruction. Nine reinterventions
      occurred in the first 2 years for stent redilation and address of aneurysms, and
      10 additional reinterventions occurred after 2 years. CONCLUSIONS: The Cheatham
      Platinum stent is safe and associated with persistent relief of aortic
      obstruction. Stent fracture and progression of fracture occur but have not
      resulted in clinically important sequelae. Reintervention is common and related
      to early and late aortic wall injury and need for re-expansion of small-diameter
      stents. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique
      identifier: NCT00552812.

PMID- 25869199
TI  - Workplace wellness recognition for optimizing workplace health: a presidential
      advisory from the American Heart Association.
AB  - The workplace is an important setting for promoting cardiovascular health and
      cardiovascular disease and stroke prevention in the United States. Well-designed,
      comprehensive workplace wellness programs have the potential to improve
      cardiovascular health and to reduce mortality, morbidity, and disability
      resulting from cardiovascular disease and stroke. Nevertheless, widespread
      implementation of comprehensive workplace wellness programs is lacking, and
      program composition and quality vary. Several organizations provide worksite
      wellness recognition programs; however, there is variation in recognition
      criteria, and they do not specifically focus on cardiovascular disease and stroke
      prevention. Although there is limited evidence to suggest that company
      performance on employer health management scorecards is associated with favorable
      healthcare cost trends, these data are not currently robust, and further
      evaluation is needed. As a recognized national leader in evidence-based
      guidelines, care systems, and quality programs, the American Heart
      Association/American Stroke Association is uniquely positioned and committed to
      promoting the adoption of comprehensive workplace wellness programs, as well as
      improving program quality and workforce health outcomes. As part of its
      commitment to improve the cardiovascular health of all Americans, the American
      Heart Association/American Stroke Association will promote science-based best
      practices for comprehensive workplace wellness programs and establish benchmarks
      for a national workplace wellness recognition program to assist employers in
      applying the best systems and strategies for optimal programming. The recognition
      program will integrate identification of a workplace culture of health and
      achievement of rigorous standards for cardiovascular health based on Life's
      Simple 7 metrics. In addition, the American Heart Association/American Stroke
      Association will develop resources that assist employers in meeting these
      rigorous standards, facilitating access to high-quality comprehensive workplace
      wellness programs for both employees and dependents, and fostering innovation and
      additional research. 

PMID- 25869200
TI  - Metal elements in the bottom sediments of the Changjiang Estuary and its adjacent
      continental shelf of the East China Sea.
AB  - The metal elements (Al, Fe, Mn, Cr, Co, Ni, Cu, Zn, As, Pb and Ca) in the bottom
      sediment of the Changjiang Estuary and its adjacent continental shelf of the East
      China Sea were studied to map their spatial distribution and to assess their
      potential risk to the marine biota. These metal concentrations except Ca were
      generally higher in the inner shelf and northeastern part, and were found to
      decrease from the coast to the offshore of the Changjiang Estuary. Sedimentary Ca
      was most abundant in the outer shelf sediments and decreased in inner shelf.
      Arsenic (As) appeared to be contaminated due to economic development from 1980s
      in the inner shelf overall, but the potential ecological risk from the selected
      metals was low in the coastal sea off the Changjiang. 

PMID- 25869201
TI  - A review of the physical impacts of sediment dispersion from aggregate dredging.
AB  - The disturbance and subsequent dispersion of sediment arising from aggregate
      dredging results in increases in suspended sediment concentrations and,
      potentially, settlement of fine sediment or sand onto the bed, which may both
      cause adverse effects on local ecology. This subject is one area which has seen
      much research over many years and this paper sets out to synthesise some basic
      general conclusions for use when assessing the significance of planned
      operations. The literature detailing the dispersion of fine sediment plumes, and
      the longer term dispersion of sand released through the dredging process, is
      scrutinised, and in some cases re-evaluated, and used to identify an evidence
      based footprint of potential impact. 

PMID- 25869202
TI  - Polycyclic aromatic hydrocarbons, polychlorinated biphenyls and organochlorine
      pesticides in European hake (Merluccius merluccius) muscle from the Western
      Mediterranean Sea.
AB  - Polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), and
      organochlorine pesticides (OCPs) were quantified in muscle tissue of European
      hake, an ecologically and commercially important species. Samples were collected
      from the Western Mediterranean, in seven different stations at different depths
      and a batch was bought in a local market. PCBs are the dominant pollutants, but
      the overall concentrations do not show significant differences between the
      different specimens analyzed from various locations, with the exception of the
      concentration of PCBs at a shallow station close to the River Besos mouth. This
      probably suggests that generally the pollutants in hake from the Western
      Mediterranean derive from historical and non-point sources. The occurrence of
      pollutants is widespread in the samples but their concentration is below
      recommended legal limits for fish or other foodstuffs. 

PMID- 25869203
TI  - DNA damage caused by organic extracts of contaminated sediment, crude, and
      weathered oil and their fractions recovered up to 5 years after the 2007 Hebei
      Spirit oil spill off Korea.
AB  - We examined the degree of DNA damage caused by three fractions (F1, aliphatic
      hydrocarbons; F2, aromatic hydrocarbons; and F3, polar compounds) of the organic
      extract of sediments taken from Taean, Korea, following the Hebei Spirit oil
      spill. DNA damage was measured using the comet assay with blood cells of the
      striped beakfish (Oplegnathus fasciatus). DNA damage was also examined for
      fractions of crude oil (Iranian Heavy Crude Oil, IHC), weathered oil and six
      subfractions (F2.1-F2.6). The greatest DNA damage was found from the Sinduri dune
      region and DNA damage decreased to 40% weathered oil in F2 fraction compared with
      crude oil. The DNA damage of the sum of fractions was found higher than the
      organic extracts of sediments, suggesting antagonistic interactions between the
      genotoxic compounds. This study confirmed the persistence of potential
      genotoxicity in sediments of the severely affected regions as long as 5 years
      after the oil spill. 

PMID- 25869204
TI  - Efficient anti-corrosive coating of cold-rolled steel in a seawater environment
      using an oil-based graphene oxide ink.
AB  - We report the production of an efficient anti-corrosive coating of cold-rolled
      (CR) steel in a seawater environment (~3.5 wt% NaCl aqueous solution) using an
      oil-based graphene oxide ink. The graphene oxide was produced by heating
      Aeschynomene aspera plant as a carbon source at 1600  degrees C in an argon
      atmosphere. The ink was prepared by cup-milling the mixture of graphene oxide and
      sunflower oil for 10 min. The coating of ink on the CR steel was made using the
      dip-coating method, followed by curing at 350  degrees C for 10 min in air
      atmosphere. The results of the potentiodynamic polarization show that the
      corrosion rate of bare CR steel decreases nearly 10,000-fold by the ink coating.
      Furthermore, the salt spray test results show that the red rusting in the ink
      coated CR steel is initiated after 100 h, in contrast to 24 h and 6 h in the case
      of oil-coated and bare CR steel, respectively. The significant decrease in the
      corrosion rate by the ink-coating is discussed based on the impermeability of
      graphene oxide to the corrosive ions.

PMID- 25869205
TI  - The effect of FAAH, MAGL, and Dual FAAH/MAGL inhibition on inflammatory and
      colorectal distension-induced visceral pain models in Rodents.
AB  - BACKGROUND: Recent studies showed that the pharmacological inhibition of
      endocannabinoid degrading enzymes such as fatty acid amide hydrolase (FAAH) and
      monoacyl glycerol lipase (MAGL) elicit promising analgesic effects in a variety
      of nociceptive models without serious side effects. However, the full spectrum of
      activities is not observed upon inhibition of either FAAH or MAGL enzymes alone
      and thus dual FAAH and MAGL inhibitors have been described. Visceral pain is
      strongly associated with inflammation and distension of the gut. Thus, we
      explored the comparable effects of FAAH, MAGL, and dual FAAH/MAGL inhibitors on
      inflammatory and mechanically evoked visceral pain models. METHODS: Visceral
      inflammatory and distension-induced pain were assessed with the 0.6% acetic acid
      writhing test in mice and colorectal distension (CRD) test in rats, respectively.
      The selective FAAH inhibitor PF 3845, MAGL inhibitor JZL 184, dual inhibitor JZL
      195, and the cannabis analog CP 55,940 were given systemically 30 min prior to
      nociceptive testing. KEY RESULTS: PF 3845 (5, 10, and 20 mg/kg), JZL 184 (5, 10,
      and 20 mg/kg), and JZL 195 (5, 10, and 20 mg/kg) elicit dose-dependent
      antinociceptive in the acetic acid writhing test. In the CRD model, while JZL 195
      (5, 10, or 20 mg/kg) and PF3845 (10, 20, and 40 mg/kg) produced dose-dependent
      antinociceptive effects comparable to those of CP 55,940 (0.1, 0.3, or 1 mg/kg),
      JZL 184 (10, 20, and 40 mg/kg) alone did not alter the visceromotor response
      (VMR). CONCLUSIONS & INFERENCES: The selective FAAH inhibitor and dual FAAH/MAGL
      inhibitors were effective in both inflammatory and mechanically evoked visceral
      pain, while the MAGL inhibitor elicited an analgesic effect in inflammatory, but
      not in distension-induced, visceral pain.

PMID- 25869206
TI  - Myc-dependent purine biosynthesis affects nucleolar stress and therapy response
      in prostate cancer.
AB  - The androgen receptor is a key transcription factor contributing to the
      development of all stages of prostate cancer (PCa). In addition, other
      transcription factors have been associated with poor prognosis in PCa, amongst
      which c-Myc (MYC) is a well-established oncogene in many other cancers. We have
      previously reported that the AR promotes glycolysis and anabolic metabolism; many
      of these metabolic pathways are also MYC-regulated in other cancers. In this
      study, we report that in PCa cells de novo purine biosynthesis and the subsequent
      conversion to XMP is tightly regulated by MYC and independent of AR activity. We
      characterized two enzymes, PAICS and IMPDH2, within the pathway as PCa biomarkers
      in tissue samples and report increased efficacy of established anti-androgens in
      combination with a clinically approved IMPDH inhibitor, mycophenolic acid (MPA).
      Treatment with MPA led to a significant reduction in cellular guanosine
      triphosphate (GTP) levels accompanied by nucleolar stress and p53 stabilization.
      In conclusion, targeting purine biosynthesis provides an opportunity to perturb
      PCa metabolism and enhance tumour suppressive stress responses. 

PMID- 25869207
TI  - PI3K inhibition synergizes with glucocorticoids but antagonizes with methotrexate
      in T-cell acute lymphoblastic leukemia.
AB  - The PI3K pathway is frequently hyperactivated in primary T-cell acute
      lymphoblastic leukemia (T-ALL) cells. Activation of the PI3K pathway has been
      suggested as one mechanism of glucocorticoid resistance in T-ALL, and patients
      harboring mutations in the PI3K negative regulator PTEN may be at increased risk
      of induction failure and relapse. By gene expression microarray analysis of T-ALL
      cells treated with the PI3K inhibitor AS605240, we identified Myc as a prominent
      downstream target of the PI3K pathway. A significant association was found
      between the AS605240 gene expression signature and that of glucocorticoid
      resistance and relapse in T-ALL. AS605240 showed anti-leukemic activity and
      strong synergism with glucocorticoids both in vitro and in a NOD/SCID xenograft
      model of T-ALL. In contrast, PI3K inhibition showed antagonism with methotrexate
      and daunorubicin, drugs that preferentially target dividing cells. This
      antagonistic interaction, however, could be circumvented by the use of correct
      drug scheduling schemes. Our data indicate the potential benefits and
      difficulties for the incorporation of PI3K inhibitors in T-ALL therapy. 

PMID- 25869208
TI  - FoxM1 promotes breast tumorigenesis by activating PDGF-A and forming a positive
      feedback loop with the PDGF/AKT signaling pathway.
AB  - The autocrine platelet-derived growth factor (PDGF)/PDGF receptor (PDGFR)
      signaling pathway promotes breast cancer tumorigenesis, but the mechanisms for
      its dysregulation in breast cancer are largely unknown. In the study, we
      identified PDGF-A as a novel transcriptional target of FoxM1. FoxM1 directly
      binds to two sites in the promoter of PDGF-A and activates its transcription.
      Mutation of these FoxM1-binding sites diminished PDGF-A promoter activity.
      Increased FoxM1 resulted in the upregulation of PDGF-A, which led to activation
      of the AKT pathway and increased breast cancer cell proliferation and
      tumorigenesis, whereas knockdown of FoxM1 does the opposite. Blocking AKT
      activation with a phosphoinositide 3-kinase/AKT inhibitor decreased FoxM1-induced
      cell proliferation. Moreover, PDGF/AKT pathway upregulates the expression of
      FoxM1 in breast cancer cells. Knockdown of PDGF-A or blockade of AKT activation
      inhibited the expression of FoxM1 in breast cancer cells. Furthermore, expression
      of FoxM1 significantly correlated with the expression of PDGF-A and the activated
      AKT signaling pathway in human breast cancer specimens. Our study demonstrates a
      novel positive regulatory feedback loop between FoxM1 and the PDGF/AKT signaling
      pathway; this loop contributes to breast cancer cell growth and tumorigenesis. 

PMID- 25869209
TI  - Ex vivo generation of myeloid-derived suppressor cells that model the tumor
      immunosuppressive environment in colorectal cancer.
AB  - Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of cells
      that accumulate in tumor-bearing subjects and which strongly inhibit anti-cancer
      immune responses. To study the biology of MDSC in colorectal cancer (CRC), we
      cultured bone marrow cells in conditioned medium from CT26 cells, which are
      genetically modified to secrete high levels of granulocyte-macrophage colony
      stimulating factor. This resulted in the generation of high numbers of CD11b(+)
      Ly6G(+) granulocytic and CD11b(+) Ly6C(+) monocytic MDSC, which closely resemble
      those found within the tumor but not the spleen of CT26 tumor-bearing mice. Such
      MDSC potently inhibited T-cell responses in vitro, a process that could be
      reversed upon blocking of arginase-1 or inducible nitric oxide synthase (iNOS).
      We confirmed that inhibition of arginase-1 or iNOS in vivo resulted in the
      stimulation of cytotoxic T-cell responses. A delay in tumor growth was observed
      upon functional repression of both enzymes. These data confirm the role of MDSC
      as inhibitors of T-cell-mediated immune responses in CRC. Moreover, MDSC
      differentiated in vitro from bone marrow cells using conditioned medium of GM-CSF
      secreting CT26 cells, represent a valuable platform to study/identify drugs that
      counteract MDSC activities.

PMID- 25869211
TI  - Muscle stem cell aging: regulation and rejuvenation.
AB  - Aging is characterized by a progressive decline of physiological integrity
      leading to the loss of tissue function and vulnerability to disease, but its
      causes remain poorly understood. Skeletal muscle has an outstanding regenerative
      capacity that relies on its resident stem cells (satellite cells). This capacity
      declines with aging, and recent discoveries have redefined our view of why this
      occurs. Here, we discuss how an interconnection of extrinsic changes in the
      systemic and local environment and cell-intrinsic mechanisms might provoke
      failure of normal muscle stem cell functions with aging. We focus particularly on
      the emergent biology of rejuvenation of old satellite cells, including cells of
      geriatric age, by restoring traits of youthfulness, with the final goal of
      improving human health during aging. 

PMID- 25869210
TI  - JAK2 inhibitor TG101348 overcomes erlotinib-resistance in non-small cell lung
      carcinoma cells with mutated EGF receptor.
AB  - Non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor
      (EGFR) mutations are responsive to EGFR-tyrosine kinase inhibitor (EGFR-TKI).
      However, NSCLC patients with secondary somatic EGFR mutations are resistant to
      EGFR-TKI treatment. In this study, we investigated the effect of TG101348 (a JAK2
      inhibitor) on the tumor growth of erlotinib-resistant NSCLC cells. Cell
      proliferation, apoptosis, gene expression and tumor growth were evaluated by
      diphenyltetrazolium bromide (MTT) assay, flow cytometry, terminal
      deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) staining,
      Western Blot and a xenograft mouse model, respectively. Results showed that
      erlotinib had a stronger impact on the induction of apoptosis in erlotinib
      sensitive PC-9 cells but had a weaker effect on erlotinib-resistant H1975 and
      H1650 cells than TG101348. TG101348 significantly enhanced the cytotoxicity of
      erlotinib to erlotinib-resistant NSCLC cells, stimulated erlotinib-induced
      apoptosis and downregulated the expressions of EGFR, p-EGFR, p-STAT3, Bcl-xL and
      survivin in erlotinib-resistant NSCLC cells. Moreover, the combined treatment of
      TG101348 and erlotinib induced apoptosis, inhibited the activation of p-EGFR and
      p-STAT3, and inhibited tumor growth of erlotinib-resistant NSCLC cells in vivo.
      Our results indicate that TG101348 is a potential adjuvant for NSCLC patients
      during erlotinib treatment. 

PMID- 25869212
TI  - Physiology and relevance of human adaptive thermogenesis response.
AB  - In homoeothermic organisms, the preservation of core temperature represents a
      primal function, and its costs in terms of energy expenditure can be
      considerable. In modern humans, the endogenous thermoregulation mechanisms have
      been replaced by clothing and environmental control, and the maintenance of
      thermoneutrality has been successfully achieved by manipulation of the micro- and
      macroenvironment. The rediscovery of the presence and activity of brown adipose
      tissue in adult humans has renewed the interest on adaptive thermogenesis (AT) as
      a means to facilitate weight loss and improve carbohydrate metabolism. The aim of
      this review is to describe the recent advancements in the study of this function,
      and to assess the potential and limitations of exploiting AT for
      environmental/behavioral, and pharmacological interventions. 

PMID- 25869213
TI  - Black joint and synovia: Histopathological evaluation of degenerative joint
      disease due to Ochronosis.
AB  - INTRODUCTION: Ochronotic arthropathy is a rapidly progressive and disabling
      arthropathy predominantly encountered after the fifth decade of life, caused by
      homogentisate1,2 dioxygenase enzyme deficiency. As it is rare disease, the
      literature on histological findings is fragmented. MATERIALS AND METHODS: We
      retrospectively re-evaluated histopathological findings in resection and/or
      curettage materials (5 hip joint, 4 knee joint, one hip joint synovium, one
      intervertebral disk and one paravertebral disk tissue) of seven ochronosis cases
      diagnosed between 1995 and 2013 in a single center. RESULTS: Necrotic brown
      chondroid detritus was present in all cases either in synovia or in subchondral
      area, some of which evoked giant cell reaction. Notably, brown pigmentation was
      prominent in upper middle parts of the articular cartilage but not that prominent
      in superficial parts and in osteochondral junction, almost stopping at the tide
      mark. Pigmentation was observed both in extracellular matrix and in cytoplasm
      either in granular or homogeneous fashion. Depositions were less prominent in
      osteophytic processes, regenerated cartilaginous areas and loose bodies. Almost
      all cases showed synovial detritic and inflammatory reaction, fibrillation,
      eburnation, and subchondral sclerosis. Disk degeneration and findings of ligament
      rupture were also observed. CONCLUSIONS: Histopathological diagnosis of
      ochronosis is not complicated given the unique "black coloring" of the affected
      tissues and it can easily be differentiated from other causes of detritic
      synovitis both clinically and histopathologically. However, there is no
      definitive cure for today and the reasons for late onset of arthropathy in
      disease course, and the mechanisms of tissue reaction to fragmented detritus
      remain elusive.

PMID- 25869214
TI  - Selective and Reversible Binding of Thiol-Functionalized Biomolecules on Polymers
      Prepared via Chemical Vapor Deposition Polymerization.
AB  - We use chemical vapor deposition polymerization to prepare a novel
      dibromomaleimide-functionalized polymer for selective and reversible binding of
      thiol-containing biomolecules on a broad range of substrates. We report the
      synthesis and CVD polymerization of 4-(3,4-dibromomaleimide)[2.2]paracyclophane
      to yield nanometer thick polymer coatings. Fourier transformed infrared
      spectroscopy and X-ray photoelectron spectroscopy confirmed the chemical
      composition of the polymer coating. The reactivity of the polymer coating toward
      thiol-functionalized molecules was confirmed using fluorescent ligands. As a
      proof of concept, the binding and subsequent release of cysteine-modified
      peptides from the polymer coating were also demonstrated via sum frequency
      generation spectroscopy. This reactive polymer coating provides a flexible
      surface modification approach to selectively and reversibly bind biomolecules on
      a broad range of materials, which could open up new opportunities in many
      biomedical sensing and diagnostic applications where specific binding and release
      of target analytes are desired. 

PMID- 25869215
TI  - Influence of extremely low frequency electromagnetic fields on growth
      performance, innate immune response, biochemical parameters and disease
      resistance in rainbow trout, Oncorhynchus mykiss.
AB  - The effects of extremely low frequency electromagnetic fields on rainbow trout
      growth performance, innate immunity and biochemical parameters were studied.
      Rainbow trout (17-18 g) were exposed to electromagnetic fields (15 Hz) at 0.01,
      0.1, 0.5, 5 and 50 uT, for 1 h daily over period of 60 days. Growth performance
      of fish improved in different treatment groups, especially at 0.1, 0.5, 5 and 50
      uT. Immunological parameters, specifically hemagglutinating titer, total
      antiprotease and alpha1-antiprotease levels in treatment groups, were also
      enhanced. Total protein and globulin contents in the serum of fish exposed to
      0.1, 0.5, 5 and 50 uT were significantly higher than those in the control group.
      No significant differences were found in serum enzyme activities, namely
      aspartate aminotransferase and alanine aminotransferase of fish in all treatment
      groups. Conversely, alkaline phosphatase level decreased in fish exposed to 0.01
      and 50 uT electromagnetic fields. Meanwhile, electromagnetic induction at 0.1,
      0.5, 5 and 50 uT enhanced fish protection against Yersinia ruckeri. These results
      indicated that these specific electromagnetic fields had possible effects on
      growth performance, nonspecific immunity and disease resistance of rainbow trout.

PMID- 25869216
TI  - Response of largemouth bass (Micropterus salmoides) from different thermal
      environments to increased water temperature.
AB  - Due to concerns of global climate change, additional research is needed to
      quantify the thermal tolerance of species, and how organisms are able to adapt to
      changes in thermal regime. We quantified the thermal tolerance and thermal stress
      response of a temperate sportfish from two different thermal environments. One
      group of largemouth bass (Micropterus salmoides) inhabited thermally enhanced
      reservoirs (used for power plant cooling), with water temperatures typically 2-5
      degrees C warmer than nearby reservoirs. We tested fish for chronic thermal
      maxima and reaction to an 8 degrees C heat shock using three common physiological
      indices of stress. We observed no evidence of differences between groups in
      thermal maxima. We observed no differences in thermal maxima between fish from
      artificially warmed and natural systems. Our results disagree with research,
      suggesting differences due to adaptation to different thermal environments. We
      speculate that behavioral modifications, lack of adequate time for genetic
      divergence, or the robust genetic plasticity of largemouth bass explain the lack
      of difference between treatment groups.

PMID- 25869218
TI  - Leadership and excellence in the early recognition of critical illness.

PMID- 25869217
TI  - Growth hormone, luteinizing hormone, and follicle-stimulating hormone regulation
      by neuropeptide Y in both sexes of the cichlid fish, Cichlasoma dimerus.
AB  - Neuropeptide Y (NPY) is considered the most potent orexigenic peptide, increasing
      before meal time and during fasting. In teleost, most studies on NPY action upon
      growth hormone (GH) and luteinizing hormone (LH) were conducted in females or
      group of animals without sex discrimination. The aim of this study was to
      evaluate whether NPY modulates the expression and release of GH and gonadotropins
      in both sexes of Cichlasoma dimerus. By double-label immunofluorescence, we first
      determined the association between NPY fibers and pituitary cells. In addition,
      we performed in vitro studies to evaluate the effect of NPY on GH and
      gonadotropins expression by real-time PCR, and release by Western blot, in males
      and females separately. Contacts between NPY fibers and GH and follicle
      stimulating hormone (FSH)-producing cells were detected, indicating possible
      functional relationships. We observed an increase in GH release in the culture
      medium at 2 nM for males (p = 0.043) and 20 nM for females (p = 0.028). Pituitary
      FSH release was stimulated at 20 nM (p = 0.026) and 200 nM (p = 0.033) for males
      and females, respectively. Finally, NPY only increased beta-LH mRNA expression at
      20 nM in females (p = 0.028) and its release at 2 nM (p = 0.049) and 200 nM for
      males (p = 0.005) and 200 nM for females (p = 0.018). In conclusion, NPY acts as
      a GH-, LH- and FSH-releasing factor, in a dose- and sex-dependent way.

PMID- 25869219
TI  - Vermont responds to its opioid crisis.
AB  - Vermont is one of the more forward-thinking states in the nation with a history
      of taking groundbreaking approaches to complex social issues. In his Jan 8, 2014
      State of the State Address, Vermont Governor Peter Shumlin announced that Vermont
      was in the midst of an opioid addiction epidemic. Though Vermont had called
      attention to its opioid crisis, it soon became clear that many other states
      shared this problem. Economic modeling of expanded access to maintenance therapy
      with either methadone or buprenorphine is felt to have "high value" because the
      added health care costs of treatment are offset by reductions in other health
      care costs that occur when individuals with opioid dependence begin treatment.
      Moreover, when broader societal costs such as criminal activity and work
      productivity are included, maintenance treatment is estimated to produce
      substantial overall savings. Coordinated efforts between the Vermont Department
      of Health's Division of Alcohol and Drug Abuse Programs (ADAP) and the Department
      of Vermont Health Access (DVHA-Vermont Medicaid Authority) have resulted in the
      creation of the Care Alliance for Opioid Addiction (or Hub & Spoke model).
      Vermont intends to develop a reproducible and exportable model based on cost
      effective, outcomes driven public policy. 

PMID- 25869220
TI  - Neighborhood, family and individual characteristics related to adolescent park
      based physical activity.
AB  - BACKGROUND: Local parks are an important community resource that may influence
      levels of physical activity among youth. However, few population-based studies
      have investigated park-based physical activity among youth. PURPOSE: This study
      examines sociodemographic, family, and neighborhood characteristics associated
      with park-based physical activity among adolescents. METHODS: Data were from the
      2007 California Health Interview Survey (CHIS), a population-based survey of
      California households, and were analyzed in 2012-2013 and 2015. This study
      examined individual (age, gender, race/ethnicity, and nativity), family
      (household income, parental education, and nativity), and neighborhood
      characteristics (urbanicity, perceived park availability, perceived park safety,
      neighborhood income, and racial composition) associated with engaging in park
      based physical activity among adolescents. RESULTS: In California, 71% of
      adolescents reported being physically active the last time they visited a park.
      In adjusted multinomial logistic regression analyses, older adolescents and
      females were less likely to be physically active in parks. Adolescents with a
      park within walking distance of home and those with a safe park nearby were more
      likely to be physically active during a park visit. CONCLUSIONS: Park
      availability and perceptions of park safety are important predictors of engaging
      in park-based physical activity among adolescents. These findings provide
      information that can help inform interventions intended to increase physical
      activity among youth. Strategies that increase availability and safety of parks
      and other recreation spaces may be particularly effective.

PMID- 25869221
TI  - Microbiological assessment of indoor air quality at different hospital sites.
AB  - Poor hospital indoor air quality (IAQ) may lead to hospital-acquired infections,
      sick hospital syndrome and various occupational hazards. Air-control measures are
      crucial for reducing dissemination of airborne biological particles in hospitals.
      The objective of this study was to perform a survey of bioaerosol quality in
      different sites in a Portuguese Hospital, namely the operating theater (OT), the
      emergency service (ES) and the surgical ward (SW). Aerobic mesophilic bacterial
      counts (BCs) and fungal load (FL) were assessed by impaction directly onto
      tryptic soy agar and malt extract agar supplemented with antibiotic
      chloramphenicol (0.05%) plates, respectively using a MAS-100 air sampler. The ES
      revealed the highest airborne microbial concentrations (BC range 240-736 CFU/m(3)
      CFU/m(3); FL range 27-933 CFU/m(3)), exceeding, at several sampling sites,
      conformity criteria defined in national legislation [6]. Bacterial concentrations
      in the SW (BC range 99-495 CFU/m(3)) and the OT (BC range 12-170 CFU/m(3)) were
      under recommended criteria. While fungal levels were below 1 CFU/m(3) in the OT,
      in the SW (range 1-32 CFU/m(3)), there existed a site with fungal indoor
      concentrations higher than those detected outdoors. Airborne Gram-positive cocci
      were the most frequent phenotype (88%) detected from the measured bacterial
      population in all indoor environments. Staphylococcus (51%) and Micrococcus (37%)
      were dominant among the bacterial genera identified in the present study.
      Concerning indoor fungal characterization, the prevalent genera were Penicillium
      (41%) and Aspergillus (24%). Regular monitoring is essential for assessing air
      control efficiency and for detecting irregular introduction of airborne particles
      via clothing of visitors and medical staff or carriage by personal and medical
      materials. Furthermore, microbiological survey data should be used to clearly
      define specific air quality guidelines for controlled environments in hospital
      settings. 

PMID- 25869222
TI  - Complementary seminovaginal microbiome in couples.
AB  - The genital tract microbiome is tightly associated with reproductive health.
      Although many research studies have been performed on the vaginal microbiome,
      current knowledge of the male microbiome is scarce, and parallel studies
      examining couples are extremely rare. In this work, we aimed to compare seminal
      and vaginal microbiomes in couples and to assess the influence of sexual
      intercourse on vaginal microbiome. The study included 23 couples. Microbiomes of
      semen and vaginal fluid (pre- and post-intercourse) were profiled using Illumina
      HiSeq2000 sequencing of the V6 region of 16S rRNA gene. Seminal communities were
      significantly more diverse, but with lower total bacterial concentrations than
      those of the vagina. Gardnerella vaginalis was predominant in half of the women
      whose partners had significant leukocytospermia, but only in one of 17 women who
      had a partner without leukocytospermia. There was significant decrease in the
      relative abundance of Lactobacillus crispatus after intercourse, and high
      concordance between semen and vaginal samples. Our data support the hypothesis
      that semen and vaginal microbiomes are in association, inasmuch as the
      predominance of G. vaginalis in female partners was significantly related to
      inflammation in male genital tracts. 

PMID- 25869223
TI  - Toxic metal resistance in biofilms: diversity of microbial responses and their
      evolution.
AB  - Since biofilms are an important issue in the fields of medicine and health,
      several recent microbiological studies have focused on their formation and their
      contribution to toxic compound resistance mechanisms. In this review, we describe
      how metals impact biofilm formation and resistance, and how biofilms can help
      cells resist toxic metals. First, the organic matrix acts as a barrier isolating
      the cells from many environmental stresses. Secondly, the metabolism of the cells
      changes, and a slowly-growing or non-growing sub-population of cells known as
      persisters emerges. Thirdly, in the case of multispecies biofilms, metabolic
      interactions are developed, allowing cells to be more persistent or to have
      greater capacity to survive than a single species biofilm. Finally, we discuss
      how the high density of the cells may promote horizontal gene transfer processes,
      resulting in the acquisition of new features. All these crucial mechanisms enable
      microorganisms to survive and colonize toxic environments, and probably
      accelerate ongoing evolutionary processes.

PMID- 25869224
TI  - Assessment of antibiotic resistance of Escherichia coli isolates and screening of
      Salmonella spp. in wild ungulates from Portugal.
AB  - Antibiotic resistance is an emerging global problem. Wild animals are rarely
      exposed to antibiotics and therefore low levels of antibiotic resistance are
      expected. However, the growing interactions of these animals with humans and
      livestock may have a huge impact on their bacterial flora. This study aimed to
      assess the levels of antibiotic resistance in Escherichia coli isolated from
      widespread wild ungulates in Portugal. The interpretation of inhibition zone
      diameters was performed according to clinical breakpoints and epidemiological cut
      offs, determined with the normalized resistance interpretation (NRI) method. For
      clinical breakpoints, 16% of the isolates were resistant to at least one
      antibiotic, including ampicillin (10%), tetracycline (9%), streptomycin (5%) co
      trimoxazole (4%), amoxicillin/clavulanic acid (1%) and cefoxitin (1%). The levels
      of resistance detected in E. coli strains isolated from wild boar were
      statistically different for ampicillin and co-trimoxasol. According to NRI cut
      offs, 10% of the population showed a non-wild-type phenotype against at least one
      antibiotic, also including tetracycline (9%), co-trimoxazole (6%), streptomycin
      (4%), ampicillin (2%) and amoxicillin/clavulanic acid (1%). Considering this
      parameter of comparison, no statistically different levels of resistance were
      identified between E. coli recovered from the three wild ungulates. Screening of
      Salmonella spp., which can be potentially pathogenic, was also performed,
      revealing that its prevalence was very low (1.5%). The study demonstrated that
      wild ungulates from Portugal are also reservoirs of antibiotic-resistant
      bacteria. 

PMID- 25869225
TI  - Phase stability, chemical bonding and mechanical properties of titanium nitrides:
      a first-principles study.
AB  - We have performed first-principles evolutionary searches for stable Ti-N
      compounds and have found, in addition to the well-known rock-salt TiN, new ground
      states Ti3N2, Ti4N3, Ti6N5 at atmospheric pressure, and Ti2N and TiN2 at higher
      pressures. The latter nitrogen-rich structure contains encapsulated N2 dumbbells
      with a N-N distance of 1.348 A at 60 GPa. TiN2 is predicted to be mechanically
      stable and quenchable. Our calculations on the mechanical properties (bulk
      modulus, shear modulus, Young's modulus, Poisson's ratio, and hardness) are in
      excellent agreement with the available experimental data. Further analyses of the
      electronic density of states, crystal orbital Hamilton population and the
      electron localization function reveal that the hardness is enhanced by
      strengthening directional covalent bonds and disappearance of Ti-Ti metallic
      bonding. 

PMID- 25869226
TI  - Superior Immunologic and Therapeutic Efficacy of a Xenogeneic Genetic Cancer
      Vaccine Targeting Carcinoembryonic Human Antigen.
AB  - We have generated a xenogeneic vaccine against human carcinoembryonic antigen
      (hCEACAM-5 or commonly hCEA) using as immunogen rhesus CEA (rhCEA). RhCEA cDNA
      was codon-usage optimized (rhCEAopt) and delivered by sequential DNA electro-gene
      transfer (DNA-EGT) and adenoviral (Ad) vector. RhCEAopt was capable to break
      tolerance to CEA in hCEA transgenic mice and immune responses were detected
      against epitopes distributed over the entire length of the protein.
      Xenovaccination with rhCEA resulted in the activation of CD4+ T-cell responses in
      addition to self-reactive CD8+ T-cells, the development of high-titer antibodies
      against hCEA, and significant antitumor effects upon challenge with hCEA+ tumor
      cells. The superior activity of rhCEAopt compared with hCEAopt was confirmed in
      hCEA/HHD double-transgenic mice, where potent CD8+ T-cell responses against
      specific human HLA A*0201 hCEA epitopes were detected. Our data show that
      xenogeneic gene-based vaccination with rhCEA is a viable approach to break
      tolerance against CEA, thus suggesting further development in the clinical
      setting. 

PMID- 25869227
TI  - A Predictive Model Using Histopathologic Characteristics of Early-Stage Type 1
      Endometrial Cancer to Identify Patients at High Risk for Lymph Node Metastasis.
AB  - BACKGROUND: This study aimed to develop a predictive model using histopathologic
      characteristics of early-stage type 1 endometrial cancer (EC) to identify
      patients at high risk for lymph node (LN) metastases. METHODS: The data of 523
      patients who received primary surgical treatment between January 2001 and
      December 2012 were abstracted from a prospective multicenter database (training
      set). A multivariate logistic regression analysis of selected prognostic features
      was performed to develop a nomogram predicting LN metastases. To assess its
      accuracy, an internal validation technique with a bootstrap approach was adopted.
      The optimal threshold in terms of clinical utility, sensitivity, specificity,
      negative predictive values (NPVs), and positive predictive values (PPVs) was
      evaluated by the receiver-operating characteristics (ROC) curve area and the
      Youden Index. RESULTS: Overall, the LN metastasis rate was 12.4 % (65/523). Lymph
      node metastases were associated with histologic grade, tumor diameter, depth of
      myometrial invasion, and lymphovascular space involvement status. These variables
      were included in the nomogram. Discrimination of the model was 0.83 [95 %
      confidence interval (CI) 0.80-0.85] in the training set. The area under the curve
      ROC for predicting LN metastases after internal validation was 0.82 (95 % CI 0.80
      0.84). The Youden Index provided a value of 0.2, corresponding to a cutoff of 140
      points (total score in the algorithm). At this threshold, the model had a
      sensitivity of 0.73 (95 % CI 0.62-0.83), a specificity of 0.84 (95 % CI 0.82
      0.85), a PPV of 0.40 (95 % CI 0.34-0.45), and an NPV of 0.95 (95 % CI 0.94-0.97).
      CONCLUSION: The results show that the risk of LN metastases can be predicted
      correctly so that patients at high risk can benefit from adapted surgical
      treatment.

PMID- 25869228
TI  - Psychological Prehabilitation Before Cancer Surgery: A Systematic Review.
AB  - BACKGROUND: Cancer patients experience anxiety and depression after diagnosis and
      during treatment. A wide range of psychological interventions have been proposed
      to alleviate distress, but the evidence about the perioperative effectiveness of
      such interventions is not clear. This systematic review examined the effect of
      preoperative psychological interventions or prehabilitation on the postoperative
      outcomes of patients undergoing surgery for cancer. METHODS: A systematic review
      of the published data was performed using Embase, Medline, and PsycInfo for the
      period from 1946 to February 2014. A total of 951 publications (case series,
      single case reports, and reviews) were found. Only seven of these studies
      included patients undergoing an operation for cancer and a preoperative
      psychological intervention. RESULTS: Six of the seven studies were randomized
      controlled trials. Four were conducted with patients who had breast cancer (n =
      356). The other studies included patients with gynecologic cancer (n = 30),
      colorectal cancer (n = 60), and prostate cancer (n = 159). Assessment of the
      studies showed four to be of good quality, two to be of moderate quality, and one
      to be of poor quality. Interventions did not affect traditional surgical outcomes
      (e.g., length of hospital stay, complications, analgesia use, or mortality) but
      positively affected patients' immunologic function. However, psychological
      interventions appeared to have an impact on patients' reported outcome measures
      including psychological outcomes, quality of life, and somatic symptoms.
      CONCLUSION: Available data suggested that preoperative psychological
      prehabilitation may have a role for cancer patients undergoing surgery. Further
      evidence is needed to evaluate its role.

PMID- 25869229
TI  - Hormones and Cancer: an exciting young journal for an expanding field of basic,
      translational, and clinical study.

PMID- 25869230
TI  - Specific binding of Clostridium perfringens enterotoxin fragment to Claudin-b and
      modulation of zebrafish epidermal barrier.
AB  - Claudins (Cldn) are the major components of tight junctions (TJs) sealing the
      paracellular cleft in tissue barriers of various organs. Zebrafish Cldnb, the
      homolog of mammalian Cldn4, is expressed at epithelial cell-cell contacts and is
      important for regulating epidermal permeability. The bacterial toxin Clostridium
      perfringens enterotoxin (CPE) has been shown to bind to a subset of mammalian
      Cldns. In this study, we used the Cldn-binding C-terminal domain of CPE (194-319
      amino acids, cCPE 194-319 ) to investigate its functional role in modulating
      zebrafish larval epidermal barriers. In vitro analyses show that cCPE 194-319
      removed Cldn4 from epithelial cells and disrupted the monolayer tightness, which
      could be rescued by the removal of cCPE 194-319. Incubation of zebrafish larvae
      with cCPE 194-319 removed Cldnb specifically from the epidermal cell membrane.
      Dye diffusion analysis with 4-kDa fluorescent dextran indicated that the
      permeability of the epidermal barrier increased due to cCPE 194-319 incubation.
      Electron microscopic investigation revealed reversible loss of TJ integrity by
      Cldnb removal. Collectively, these results suggest that cCPE 194-319 could be
      used as a Cldnb modulator to transiently open the epidermal barrier in zebrafish.
      In addition, zebrafish might be used as an in vivo system to investigate the
      capability of cCPE to enhance drug delivery across tissue barriers.

PMID- 25869231
TI  - LONG-TERM OUTCOME OF MINDFULNESS-BASED COGNITIVE THERAPY IN RECURRENTLY DEPRESSED
      PATIENTS WITH AND WITHOUT A DEPRESSIVE EPISODE AT BASELINE.
AB  - BACKGROUND: In a previous randomized controlled trial in patients with three or
      more previous depressive episodes, mindfulness-based cognitive therapy (MBCT)
      appeared to be equally effective in those who were depressed and those who were
      in remission at the start of the trial. AIM: The aim of this study is to compare
      the 1-year outcome of MBCT in 124 remitted and 58 depressed patients who
      participated in the original trial and who were all offered MBCT either
      immediately or after a waiting period of 3 months. METHODS: The course of
      depressive symptoms, rumination, mindfulness skills, and quality of life over the
      course of treatment and the 1-year follow-up period was analyzed. Linear mixed
      modeling was used to compare the outcome between remitted and depressed patients
      at baseline. RESULTS: In the whole sample, levels of depression and rumination
      decreased and mindfulness and quality of life increased over treatment. Levels of
      depressive symptoms, mindfulness, and quality of life remained stable over the 1
      year follow-up period. Rumination further decreased. Remitted and depressed
      patients at the start of the trial did not differ in terms of outcome during or
      after treatment. CONCLUSIONS: Long-term outcome after MBCT in depressed patients
      was comparable to those who were in remission at the start of the trial. These
      findings lend further support to the notion that recurrent depressed patients
      meeting the criteria of a depressive episode do not need to be excluded from
      MBCT.

PMID- 25869232
TI  - Associations between socio-economic status and dietary patterns in US black and
      white adults.
AB  - Socio-economic status (SES) has been associated with measures of diet quality;
      however, such measures have not directly captured overall eating practices in
      individuals. Based on the factor analysis of fifty-six food groups from FFQ,
      associations between patterns of food consumption and SES were examined in a
      nationwide sample of 17,062 black (34.6%) and white participants (age >45 years)
      from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study.
      Logistic regression models adjusted for age, sex, racial group and geographic
      region were used to examine adherence to five emergent dietary patterns
      (convenience, plant-based, sweets/fats, southern and alcohol/salads) according to
      four levels each of individual education, household income and community-level
      SES. Further models assessed adherence to these dietary patterns by racial group,
      and an overall model including both racial groups examined whether the
      relationships between SES and adherence to these dietary patterns differed among
      black and white participants. For all the three measures of SES, higher SES had
      been associated with greater adherence to plant-based and alcohol/salads
      patterns, but lower adherence to sweets/fats and southern patterns. Statistically
      significant differences between black and white participants were observed in the
      associations between household income and adherence to alcohol/salads, individual
      education and adherence to plant-based and sweets/fats, and community SES and
      adherence to convenience patterns. As adherence to dietary patterns has been
      shown to be associated with health outcomes in this population (e.g. stroke), the
      present study offers valuable insight into behavioural and environmental factors
      that may contribute to health disparities in the diverse US population.

PMID- 25869234
TI  - Innovative Methods for the Benefit of Public Health Using Space Technologies for
      Disaster Response.
AB  - Space applications have evolved to play a significant role in disaster relief by
      providing services including remote sensing imagery for mitigation and disaster
      damage assessments; satellite communication to provide access to medical
      services; positioning, navigation, and timing services; and data sharing. Common
      issues identified in past disaster response and relief efforts include lack of
      communication, delayed ordering of actions (eg, evacuations), and low levels of
      preparedness by authorities during and after disasters. We briefly summarize the
      Space for Health (S4H) Team Project, which was prepared during the Space Studies
      Program 2014 within the International Space University. The S4H Project aimed to
      improve the way space assets and experiences are used in support of public health
      during disaster relief efforts. We recommend an integrated solution based on nano
      satellites or a balloon communication system, mobile self-contained relief units,
      portable medical scanning devices, and micro-unmanned vehicles that could
      revolutionize disaster relief and disrupt different markets. The recommended new
      system of coordination and communication using space assets to support public
      health during disaster relief efforts is feasible. Nevertheless, further actions
      should be taken by governments and organizations in collaboration with the
      private sector to design, test, and implement this system.

PMID- 25869233
TI  - Preclinical screening of anticancer drugs using infrared (IR) microspectroscopy.
AB  - High-throughput label-free technologies such as IR microscopy can objectively
      assess the effect of drugs upon cellular systems, offering the potential of a
      valuable preclinical tool that can aid in the drug development process. 

PMID- 25869235
TI  - Comparison of Outcomes for Osteochondral Lesions of the Talus With and Without
      Chronic Lateral Ankle Instability.
AB  - BACKGROUND: Previous reports suggest that prolonged instability of the ankle may
      contribute to development of osteochondral lesions and eventually lead to
      osteoarthritis. However, no studies have directly compared osteochondral lesions
      in ankles with chronic lateral ankle instability (CLAI) to those without
      instability. This study was performed to determine characteristics and resulting
      clinical outcomes associated with osteochondral lesions of the talus (OLT) in
      patients with and without instability. METHODS: Of 420 patients who underwent
      primary arthroscopic marrow stimulation for OLT, 74 patients were identified as
      having concomitant CLAI. After considering age, sex, body mass index, and initial
      trauma history for the propensity score (1:2 ratio), a total of 148 patients
      without CLAI were matched from the remainder of the cohort. Demographics and
      lesion characteristics were compared using preoperative magnetic resonance
      imaging (MRI) and arthroscopy. Clinical outcomes were compared using a visual
      analog scale (VAS), the American Orthopaedic Foot & Ankle Society (AOFAS) ankle
      score, and the Foot and Ankle Outcome Score (FAOS). RESULTS: The OLT group with
      CLAI presented a significantly increased proportion of lateral-side OLT, large
      OLT (150 mm(2) or larger), and chondral lesions at the tip of the medial
      malleolus (P = .018, P = .024, and P < .001, respectively). VAS and AOFAS scores
      were comparable at the last follow-up. However, the OLT with CLAI group also
      exhibited a significantly increased proportion of failure (AOFAS score less than
      80) and inferior outcomes in the FAOS for the sport and recreation subscale (P =
      .034 and P = .005, respectively). CONCLUSIONS: Compared with osteochondral
      lesions in ankles without CLAI, osteochondral lesions in an unstable ankle had an
      increased proportion of larger lesions (150 mm(2) or larger) and additional
      chondral lesions at the tip of the medial malleolus and the tibia plafond. This
      group also displayed increased clinical failure (AOFAS score less than 80).
      Inferior performance in sport and recreational activities may be more likely in
      patients with both OLT and CLAI. LEVEL OF EVIDENCE: Level III, retrospective
      cohort study.

PMID- 25869236
TI  - Temperature-triggered chemical switching growth of in-plane and vertically
      stacked graphene-boron nitride heterostructures.
AB  - In-plane and vertically stacked heterostructures of graphene and hexagonal boron
      nitride (h-BN-G and G/h-BN, respectively) are both recent focuses of graphene
      research. However, targeted synthesis of either heterostructure remains a
      challenge. Here, via chemical vapour deposition and using benzoic acid precursor,
      we have achieved the selective growth of h-BN-G and G/h-BN through a temperature
      triggered switching reaction. The perfect in-plane h-BN-G is characterized by
      scanning tunnelling microscopy (STM), showing atomically patched graphene and h
      BN with typical zigzag edges. In contrast, the vertical alignment of G/h-BN is
      confirmed by unique lattice-mismatch-induced moire patterns in high-resolution
      STM images, and two sets of aligned selected area electron diffraction spots,
      both suggesting a van der Waals epitaxial mechanism. The present work
      demonstrates the chemical designability of growth process for controlled
      synthesis of graphene and h-BN heterostructures. With practical scalability, high
      uniformity and quality, our approach will promote the development of graphene
      based electronics and optoelectronics. 

PMID- 25869237
TI  - Differences in Gut Microbiota Between Atopic and Healthy Children.
AB  - Although gut microbiota has been studied relatively extensively in the context of
      allergic diseases, there have been several contradictions between these studies.
      By applying high-throughput sequencing, we aimed to analyze the differences in
      gut microbiota between atopic and healthy children at 5 and 12 years of age. 51
      stool samples were collected from 14 atopic and 15 healthy children and analyzed
      with 454 pyrosequencing of the 16S rRNA gene. At the ages of 5 and 12 years,
      Bacteroides, Prevotella, and Dialister dominated gut microbiota in both atopic
      and healthy groups of children. Children in the atopic group had lower abundance
      and prevalence of Akkermansia in gut microbiota than their healthy counterparts.
      Thus, the composition of gut microbiota does not seem to be significantly
      different between atopic and healthy children, but lower abundance and prevalence
      of Akkermansia indicate that this bacterium may accompany or play a role in IgE
      mediated atopic diseases. 

PMID- 25869238
TI  - Development and implementation of a clinical pathway approach to simulation-based
      training for foregut surgery.
AB  - INTRODUCTION: Contemporary demands on resident education call for integration of
      simulation. We designed and implemented a simulation-based curriculum for Post
      Graduate Year 1 surgery residents to teach technical and nontechnical skills
      within a clinical pathway approach for a foregut surgery patient, from outpatient
      visit through surgery and postoperative follow-up. METHODS: The 3-day curriculum
      for groups of 6 residents comprises a combination of standardized patient
      encounters, didactic sessions, and hands-on training. The curriculum is
      underpinned by a summative simulation "pathway" repeated on days 1 and 3. The
      "pathway" is a series of simulated preoperative, intraoperative, and
      postoperative encounters in following up a single patient through a disease
      process. The resident sees a standardized patient in the clinic presenting with
      distal gastric cancer and then enters an operating room to perform a
      gastrojejunostomy on a porcine tissue model. Finally, the resident engages in a
      simulated postoperative visit. All encounters are rated by faculty members and
      the residents themselves, using standardized assessment forms endorsed by the
      American Board of Surgery. RESULTS: A total of 18 first-year residents underwent
      this curriculum. Faculty ratings of overall operative performance significantly
      improved following the 3-day module. Ratings of preoperative and postoperative
      performance were not significantly changed in 3 days. Resident self-ratings
      significantly improved for all encounters assessed, as did reported confidence in
      meeting the defined learning objectives. CONCLUSIONS: Conventional surgical
      simulation training focuses on technical skills in isolation. Our novel "pathway"
      curriculum targets an important gap in training methodologies by placing both
      technical and nontechnical skills in their clinical context as part of managing a
      surgical patient. Results indicate consistent improvements in assessments of
      performance as well as confidence and support its continued usage to educate
      surgery residents in foregut surgery.

PMID- 25869239
TI  - Inhibited fragmentation of mAbs in buffered ionic liquids.
AB  - We thoroughly investigated the biological, structural and chemical stability of
      epidermal growth factor receptor monoclonal antibody (EGFR mAb) using choline
      based buffered ionic liquids (BILs). The results demonstrated substantially
      enhanced stabilities in our BILs, indicating their huge promise as real-world
      green biological buffers for antibody storage and transportation. 

PMID- 25869240
TI  - The forgotten role of glucose effectiveness in the regulation of glucose
      tolerance.
AB  - Glucose effectiveness (SG) is the ability of glucose per se to stimulate its own
      uptake and to suppress its own production under basal/constant insulin
      concentrations. In an individual, glucose tolerance is a function of insulin
      secretion, insulin action and SG. Under conditions of declining insulin secretion
      and action (e.g. type 2 diabetes), the degree of SG assumes increasing
      significance in determining the level of glucose tolerance both in fasted and
      postprandial states. Although the importance of SG has been recognized for years,
      mechanisms that contribute to SG are poorly understood. Research data on
      modulation of SG and its impact in glucose intolerance is limited. In this
      review, we will focus on the role of SG in the regulation of glucose tolerance,
      its evaluation, and potential advantages of therapies that can enhance glucose
      induced stimulation of glucose uptake and suppression of its own production in
      conditions of impaired insulin secretion and action.

PMID- 25869241
TI  - Evaluation of the clinical success of class I cavities prepared by an Er:YAG
      laser-5-year follow-up study.
AB  - The purpose of this study was to evaluate, after 5 years, the clinical success of
      preparing class 1 composite resin restorations with an Er:YAG laser. Sixty-five
      teeth of 30 patients were included in the study, and an Er:YAG laser emitting at
      a wavelength of 2.94 MUm was used for the class I cavity preparations with not
      more than one third of the mesiodistal width of the occlusal surfaces of each
      tooth. All cavities were restored with a light-cured composite resin, following a
      single bond application. After the baseline examination, restorations were
      reevaluated by the same experienced clinician after 5 years, using the modified
      Ryge criteria. At the end of 5 years, 41 of the 65 restorations were evaluated in
      22 patients and scored. With respect to marginal discoloration, anatomic form,
      color match, and surface texture, significant differences were found between
      baselines tested after 5 years. Clinical evaluation of postoperative sensitivity
      showed that 90.2 % were rated as alpha. All restorations evaluated in this study
      demonstrated acceptable clinical performance within the evaluation period based
      on the alpha and bravo ratings for clinically satisfactory restorations. Further
      evaluations are necessary for a better clinical performance analysis.

PMID- 25869242
TI  - Identification and characterization of metabolites of ASP015K, a novel oral Janus
      kinase inhibitor, in rats, chimeric mice with humanized liver, and humans.
AB  - 1. Here, we elucidated the structure of metabolites of novel oral Janus kinase
      inhibitor ASP015K in rats and humans and evaluated the predictability of human
      metabolites using chimeric mice with humanized liver (PXB mice). 2. Rat
      biological samples collected after oral dosing of (14)C-labelled ASP015K were
      examined using a liquid chromatography-radiometric detector and mass spectrometer
      (LC-RAD/MS). The molecular weight of metabolites in human and the liver chimeric
      mouse biological samples collected after oral dosing of non-labelled ASP015K was
      also investigated via LC-MS. Metabolites were also isolated from rat bile samples
      and analyzed using nuclear magnetic resonance. 3. Metabolic pathways of ASP015K
      in rats and humans were found to be glucuronide conjugation, methyl conjugation,
      sulfate conjugation, glutathione conjugation, hydroxylation of the adamantane
      ring and N-oxidation of the 1H-pyrrolo[2,3-b]pyridine ring. The main metabolite
      of ASP015K in rats was the glucuronide conjugate, while the main metabolite in
      humans was the sulfate conjugate. Given that human metabolites were produced by
      human hepatocytes in chimeric mice with humanized liver, this human model mouse
      was believed to be useful in predicting the human metabolic profile of various
      drug candidates. 

PMID- 25869243
TI  - Salvianolic acid B as a substrate and weak catechol-O-methyltransferase inhibitor
      in rats.
AB  - 1. The aim of this study was to investigate the biotransformation of salvianolic
      acid B (SAB) by catechol-O-methyltransferase (COMT) and its interaction with
      levodopa (l-DOPA) methylation in rats. 2. The enzyme kinetics of SAB were studied
      after incubation with rat COMT. The in vivo SAB and 3-monomethyl-SAB (3-MMS)
      levels were determined after a single dose of tolcapone with or without SAB
      administration. For l-DOPA, the effect of SAB inhibition on l-DOPA methylation
      was studied in vitro. The l-DOPA and 3-O-methyldopa (3-OMD) levels were
      determined after single and multiple doses of SAB with or without l-DOPA
      administration. 3. After incubation, we found that SAB was methylated mainly by
      rat liver and kidney COMT. Tolcapone strongly inhibited the formation of 3-MMS in
      vitro and in vivo, without any change in the plasma concentration of SAB.
      Moreover, tolcapone significantly increased the cumulative bile excretion of SAB
      from 3% to 40% in the rat. SAB inhibited the methylation of l-DOPA with an IC50
      value of 2.08 MUM in vitro. In vivo, a single intravenous dose of SAB decreased
      the plasma concentration of 3-OMD, with no obvious effect on the pharmacokinetics
      of l-DOPA. Multiple doses of SAB given to rats also decreased the plasma
      concentration of 3-OMD, while SAB increased the plasma concentration of l-DOPA. 

PMID- 25869244
TI  - Distribution and pharmacokinetics of etamicastat and its N-acetylated metabolite
      (BIA 5-961) in dog and monkey.
AB  - 1. The disposition etamicastat was evaluated in the Cynomolgus monkey after
      intravenous and oral administration of [(14)C]-etamicastat. The pharmacokinetics
      of etamicastat and its N-acetylated metabolite BIA 5-961 were also evaluated in
      monkeys and dogs. 2. In the monkey, 7 days after intravenous and oral
      administration of [(14)C]-etamicastat, 76.6-91.1% of the etamicastat-related
      radioactivity had been excreted mainly in urine. The radioactivity peaked in
      plasma between 4- and 8-h post-dosing followed by a quick decline and a slow
      terminal phase (half-life of 68.7 h). The calculated oral bioavailability for
      etamicastat was 46.1%. Etamicastat was quickly absorbed in monkeys and dogs with
      a half-life ranging from 5.2 to 9.9 h in monkeys and 6.9 to 11.4 h in dogs over.
      3. The N-acetylated metabolite of etamicastat, represented 4-7% of the extent of
      exposure of etamicastat in the monkey, but was not found detectable in dogs.
      Gender did not influence etamicastat exposure and the concentration versus time
      curves fitted a dose-dependent pharmacokinetics in the dog, but not in the
      monkey. 4. In conclusion, etamicastat is rapidly absorbed and primarily excreted
      via urine in monkeys. Similarly, to humans, monkeys, unlike dogs, N-acetylate
      etamicastat and evidence that etamicastat pharmacokinetics is less than dose
      proportional.

PMID- 25869246
TI  - In vitro effects of standardized extract of Bacopa monniera and its five
      individual active constituents on human P-glycoprotein activity.
AB  - 1. For centuries Bacopa monniera (BM) has been used as an herbal drug for the
      treatment of various mental ailments. A chemically standardized alcoholic extract
      of BM is clinically available over the counter herbal remedy for memory
      enhancement in children and adults. Consumption of herbal preparations has been
      reported to alter the function of membrane transporters, especially P
      glycoprotein (P-gp), ATP-dependent drug efflux transporter responsible for the
      development of herb-drug interactions. 2. In the present study, we evaluated the
      in vitro effect of BM extract and its five individual active constituents
      (namely, bacopaside I, bacopaside II and bacopasaponin C, bacoside A and bacoside
      A3) on P-gp function using luminescent P-gp ATPase assay and Rh123 transport
      assay across human MDR1 gene transfected LLC-GA5-COL150 cell line. 3. It was
      observed that BM extract and its five individual constituents inhibited both
      basal activity as well as verapamil-stimulated ATPase activity, suggesting their
      affinity towards P-gp. Further, BM and its five active constituents inhibited the
      rhodamine 123 (Rh123) transport across LLC-GA5-COL150 cell monolayer with
      bacopaside II being the most potent inhibitor of P-gp, which decreased P-gp
      efflux ratio of Rh123 by fourfold in comparison to control. 4. Our finding may
      prove beneficial in predicting the potential herb-drug interactions of BM on
      concomitant medication with P-gp substrate drugs in clinical settings.

PMID- 25869245
TI  - Irreversible binding of an anticancer compound (BI-94) to plasma proteins.
AB  - 1. We investigated the mechanisms responsible for the in vivo instability of a
      benzofurazan compound BI-94 (NSC228148) with potent anti-cancer activity. 2. BI
      94 was stable in MeOH, water, and in various buffers at pHs 2.5-5, regardless of
      the buffer composition. In contrast, BI-94 was unstable in NaOH and at pHs 7-9,
      regardless of the buffer composition. BI-94 disappeared immediately after spiking
      into mice, rat, monkey, and human plasma. BI-94 stability in plasma can be only
      partially restored by acidifying it, which indicated other mechanisms in addition
      to pH for BI-94 instability in plasma. 3. BI-94 formed adducts with the trapping
      agents, glutathione (GSH) and N-acetylcysteine (NAC), in vivo and in vitro via
      nucleophilic aromatic substitution reaction. The kinetics of adduct formation
      showed that neutral or physiological pHs enhanced and accelerated GSH and NAC
      adduct formation with BI-94, whereas acidic pHs prevented it. Therefore,
      physiological pHs not only altered BI-94 chemical stability but also enhanced
      adduct formation with endogenous nucleophiles. In addition, adduct formation with
      human serum albumin-peptide 3 (HSA-T3) at the Cys34 position was demonstrated. 4.
      In conclusion, BI-94 was unstable at physiological conditions due to chemical
      instability and irreversible binding to plasma proteins.

PMID- 25869247
TI  - Pharmacokinetics and tissue distribution of the new non-imidazole histamine H3
      receptor antagonist 1-[3-(4-tert-butylphenoxy) propyl]piperidine in rats.
AB  - 1. The aim of this study was to evaluate pharmacokinetics and tissue distribution
      of novel histamine H3 receptor antagonist 1-[3-(4-tert
      butylphenoxy)propyl]piperidine (compound DL76). 2. Following intravenous
      administration of DL76 at the dose of 3 mg/kg, pharmacokinetic parameters were
      calculated using non-compartmental analysis. The systemic serum clearance was
      10.08 L/h/kg and the estimated blood clearance was 5.64 L/h/kg. The volume of
      distribution at steady state was 16.1 L/kg which was greater than total body
      water, terminal half-life and MRT equalled 1.41 h and 1.6 h, respectively. The
      two-compartment pharmacokinetic model with enterohepatic circulation was also
      successfully fitted to the experimental data. 3. After systemic administration,
      DL76 was rapidly distributed into all organs studied (liver, kidney, brain, and
      lung). The highest AUC of DL76 was observed in lungs followed by brain, where the
      exposure to the investigated compound expressed as AUC was almost 30 times higher
      than in serum. 4. Bioavailability, calculated based on the area-under-the
      concentration-time curve extrapolated to infinity after intravenous and
      intragastric administration of the dose 3 mg/kg, equalled 60.9%.

PMID- 25869249
TI  - Involvement of CAR and PXR in the transcriptional regulation of CYP2B6 gene
      expression by ingredients from herbal medicines.
AB  - 1. Induction of hepatic drug-metabolizing enzymes can affect drug efficacy and
      cause toxicity. However, so far, limited information is available regarding the
      molecular mechanism how herbal medicines induce human CYP2B6, which metabolizes
      many of the clinically used therapeutics and activates several pro-carcinogens or
      toxicants. Accumulated evidence suggests that the human constitutive androstane
      receptor (hCAR) and the human pregnane X receptor (hPXR) play important roles in
      trans-activation of CYP2B6. In this study, we investigated the effects of 68
      Chinese herbal ingredients on the receptor specificity of hPXR/hCAR-mediated
      CYP2B6 induction by luciferase reporter gene assays in transiently transfected
      HepG2 cells and on the expression of CYP2B6 in LS174T cells. 2. The HepG2 cells
      were transiently transfected with human CYP2B6 luciferase promoter reporter
      plasmids along with hPXR or hCAR3. The results indicated that apigenin (Api),
      curcumol (Cur) and praeruptorin A (Pra A) were identified as potent activators of
      hPXR, and Pra A was also a ligand of hCAR. 3. Furthermore, CYP2B6 mRNA expression
      in LS174T cells treated with the three herbal ingredients was determined by real
      time polymerase chain reaction. By combining western blot and LC-MS/MS, CYP2B6
      protein expression and catalytic activity induced by the three herbal ingredients
      were measured. 4. Our observation showed Api and Cur up-regulated CYP2B6
      expression by transactivation of hPXR, and Pra A acted as the ligand of both hPXR
      and hCAR to induce CYP2B6 expression. 

PMID- 25869248
TI  - Time course of acetaminophen-protein adducts and acetaminophen metabolites in
      circulation of overdose patients and in HepaRG cells.
AB  - 1. It has been suggested that acetaminophen (APAP)-protein adducts can be
      measured in circulation to diagnose APAP-induced liver injury. However, the full
      time course of plasma adducts has not been studied specifically in early
      presenting overdose patients. In fact, surprisingly little work has been done on
      the metabolism of APAP after overdose in general. 2. We measured APAP, five APAP
      metabolites and APAP-protein adducts in plasma samples from early- and late
      presenting overdose patients, and APAP-protein adducts in culture medium from
      HepaRG cells. 3. In contrast to earlier rodents studies, we found that APAP
      protein adducts were lower at early time points and peaked around the time of
      peak liver injury, suggesting that these adduct levels may take longer to become
      elevated or remain elevated than previously thought. 4. APAP and its major
      metabolites were elevated in plasma at early time points and rapidly decreased.
      5. Although clinical measurement of APAP-protein adducts holds promise as a
      diagnostic tool, we suggest caution in its interpretation in very early
      presenting patients. Our data also support the idea that sulfation is saturated
      even at low doses but glucuronidation has a much higher capacity, highlighting
      the importance of glucuronidation in APAP metabolism.

PMID- 25869250
TI  - Effects of CYP3A5 genotypes, ABCB1 C3435T and G2677T/A polymorphism on
      pharmacokinetics of Tacrolimus in Chinese adult liver transplant patients.
AB  - 1. The purpose of this study was to establish a population pharmacokinetic (PK)
      model of tacrolimus and evaluate the influence of clinical covariates, including
      the genetic polymorphisms of the cytochrome P450 3A5 gene (CYP3A5) and gene
      encoding P-glycoprotein (ABCB1), on the PK parameters in Chinese adult liver
      transplant recipients. 2. Details of drug dose, sampling times and concentrations
      were collected retrospectively from routine therapeutic drug monitoring data
      early after liver transplant. Tacrolimus PKs was studied by a non-linear mixed
      effect modeling (NONMEM) method. CYP3A5 genotypes, ABCB1 C3435T and G2677T/A
      polymorphism and a number of clinical covariates were tested for their influence
      on TAC PKs. 3. A one-compartment model with first-order absorption and
      elimination adequately described the data. Apparent clearance (CL/F) and apparent
      volumes of distribution (V/F) in final population model were 17.6 L/h and 225 L,
      respectively. The absorption rate constant (Ka) was fixed at 4.48 h(-1). The
      inter-individual variability in CL/F and V/F was 53.9 and 68%, respectively. In
      the final model, CYP3A5 genotype, post-operative day, alanine aminotransferase,
      total bilirubin, hematocrit and blood urea nitrogen were found to significantly
      influence the CL/F, whereas POD and HB influence V/F. 4. Population PK analysis
      of tacrolimus in Chinese adult liver transplant patients resulted in
      identification of the CYP3A5 genotype, POD, BUN, ALP, HCT, TBIL and HB as
      significant covariates on the PK parameters of tacrolimus. 

PMID- 25869251
TI  - Mass spectrometry for the elucidation of the subtle molecular structure of
      biodegradable polymers and their degradation products.
AB  - Contemporary reports by Polish authors on the application of mass spectrometric
      methods for the elucidation of the subtle molecular structure of biodegradable
      polymers and their degradation products will be presented. Special emphasis will
      be given to natural aliphatic (co)polyesters (PHA) and their synthetic analogues,
      formed through anionic ring-opening polymerization (ROP) of beta-substituted beta
      lactones. Moreover, the application of MS techniques for the evaluation of the
      structure of biodegradable polymers obtained in ionic and coordination
      polymerization of cyclic ethers and esters as well as products of step-growth
      polymerization, in which bifunctional or multifunctional monomers react to form
      oligomers and eventually long chain polymers, will be discussed. Furthermore, the
      application of modern MS techniques for the assessment of polymer degradation
      products, frequently bearing characteristic end groups that can be revealed and
      differentiated by MS, will be discussed within the context of specific
      degradation pathways. Finally, recent Polish accomplishments in the area of mass
      spectrometry will be outlined.

PMID- 25869252
TI  - [How does one write a university history?].

PMID- 25869253
TI  - Stretchable, Transparent, Ultrasensitive, and Patchable Strain Sensor for Human
      Machine Interfaces Comprising a Nanohybrid of Carbon Nanotubes and Conductive
      Elastomers.
AB  - Interactivity between humans and smart systems, including wearable, body
      attachable, or implantable platforms, can be enhanced by realization of
      multifunctional human-machine interfaces, where a variety of sensors collect
      information about the surrounding environment, intentions, or physiological
      conditions of the human to which they are attached. Here, we describe a
      stretchable, transparent, ultrasensitive, and patchable strain sensor that is
      made of a novel sandwich-like stacked piezoresisitive nanohybrid film of single
      wall carbon nanotubes (SWCNTs) and a conductive elastomeric composite of
      polyurethane (PU)-poly(3,4-ethylenedioxythiophene) polystyrenesulfonate ( PEDOT:
      PSS). This sensor, which can detect small strains on human skin, was created
      using environmentally benign water-based solution processing. We attributed the
      tunability of strain sensitivity (i.e., gauge factor), stability, and optical
      transparency to enhanced formation of percolating networks between conductive
      SWCNTs and PEDOT phases at interfaces in the stacked PU-PEDOT:PSS/SWCNT/PU
      PEDOT:PSS structure. The mechanical stability, high stretchability of up to 100%,
      optical transparency of 62%, and gauge factor of 62 suggested that when attached
      to the skin of the face, this sensor would be able to detect small strains
      induced by emotional expressions such as laughing and crying, as well as eye
      movement, and we confirmed this experimentally.

PMID- 25869254
TI  - The emerging role of calcium-modulating cyclophilin ligand in posttranslational
      insertion of tail-anchored proteins into the endoplasmic reticulum membrane.
AB  - Tail-anchored (TA) proteins, a class of membrane proteins having an N-terminal
      cytoplasmic region anchored to the membrane by a single C-terminal transmembrane
      domain, are posttranslationally inserted into the endoplasmic reticulum (ER)
      membrane. In yeasts, the posttranslational membrane insertion is mediated by the
      Guided Entry of TA Proteins (GET) complex. Get3, a cytosolic ATPase, targets
      newly synthesized TA proteins to the ER membrane, where Get2 and Get3 constitute
      the Get3 receptor driving the membrane insertion. While mammalian cells employ
      TRC40 and WRB, mammalian homologs of Get3 and Get1, respectively, they lack the
      gene homologous to Get2. We recently identified calcium-modulating cyclophilin
      ligand (CAML) as a TRC40 receptor, indicating that CAML was equivalent to Get2 in
      the context of the membrane insertion. On the other hand, CAML has been well
      characterized as a signaling molecule that regulates various biological
      processes, raising the question of how the two distinct actions of CAML, the
      membrane insertion and the signal transduction, are assembled. In this review, we
      summarize recent progress of the molecular mechanism of the membrane insertion of
      TA proteins and discuss the possibility that CAML could sense the various signals
      at the ER membrane, thereby controlling TA protein biogenesis. 

PMID- 25869255
TI  - The role of the acidic domain of alpha-synuclein in amyloid fibril formation: a
      molecular dynamics study.
AB  - The detailed mechanism of the pathology of alpha-synuclein in the Parkinson's
      disease has not been clearly elucidated. Recent studies suggested a possible
      chaperone-like role of the acidic C-terminal region of alpha-synuclein in the
      formation of amyloid fibrils. It was also previously demonstrated that the alpha
      synuclein amyloid fibril formation is accelerated by mutations of proline
      residues to alanine in the acidic region. We performed replica exchange molecular
      dynamics simulations of the acidic and nonamyloid component (NAC) domains of the
      wild type and proline-to-alanine mutants of alpha-synuclein under various
      conditions. Our results showed that structural changes induced by a change in pH
      or an introduction of mutations lead to a reduction in mutual contacts between
      the NAC and acidic regions. Our data suggest that the highly charged acidic
      region of alpha-synuclein may act as an intramolecular chaperone by protecting
      the hydrophobic domain from aggregation. Understanding the function of such
      chaperone-like parts of fibril-forming proteins may provide novel insights into
      the mechanism of amyloid formation. 

PMID- 25869256
TI  - Acceptance of vulvovaginal pain in women with provoked vestibulodynia and their
      partners: associations with pain, psychological, and sexual adjustment.
AB  - INTRODUCTION: Provoked vestibulodynia (PVD) is a common vulvovaginal pain
      condition associated with negative psychological and sexual consequences for
      affected women and their sexual partners. Greater pain acceptance has been found
      to be associated with better functional and psychological outcomes in individuals
      with chronic pain, and acceptance-based strategies are being increasingly
      incorporated into treatment protocols. The present study is a novel investigation
      of pain acceptance in PVD couples. AIM: The aim was to examine the associations
      between acceptance of vulvovaginal pain and women's pain during intercourse, as
      well as the psychological and sexual adjustment of both women with PVD and their
      partners. METHODS: Sixty-one couples (M(age) for women = 27.95 years, SD = 5.87;
      M(age) for men = 30.48 years, SD = 6.70) in which the woman was diagnosed with
      PVD completed the Chronic Pain Acceptance Questionnaire, in reference to women's
      vulvovaginal pain. Women also rated their pain during intercourse, and couples
      completed measures of anxiety, depression, sexual function, and sexual
      satisfaction. MAIN OUTCOME MEASURES: Dependent measures were (i) women's self
      reported pain during intercourse on a numerical rating scale; (ii) State-Trait
      Anxiety Inventory trait subscale; (iii) Beck Depression Inventory-II; (iv)
      Derogatis Interview for Sexual Functioning; and (v) Global Measure of Sexual
      Satisfaction Scale. RESULTS: Women's greater pain acceptance was associated with
      their lower self-reported pain during intercourse, controlling for partner's pain
      acceptance. Greater pain acceptance among women was associated with their own
      lower anxiety and depression, greater sexual functioning, as well as their own
      and their partner's greater sexual satisfaction, controlling for the partner's
      pain acceptance. Additionally, greater pain acceptance among male partners was
      associated with their own lower depression. CONCLUSIONS: Findings suggest that
      psychological interventions for PVD should target increasing couples'
      vulvovaginal pain acceptance in order to improve women's pain and the sexual and
      psychological functioning of both members of the couple.

PMID- 25869257
TI  - A New Dawn for Bladder Cancer? Recommendations from the National Institute for
      Health and Care Excellence (NICE) on Managing Bladder Cancer.

PMID- 25869258
TI  - Information Concerning Endocrine Therapy and Adherence of Patients with Breast
      and Prostate Cancer.

PMID- 25869259
TI  - Metastatic Ablation for Sarcomas: Methodological and Ethical Dilemmas for
      Prospective Studies.

PMID- 25869260
TI  - Adhesive small-bowel obstruction treatment using internal intestinal splinting
      with a nasointestinal ileus tube.
AB  - AIM: The aim of this paper was to investigate the effect of non-surgical internal
      intestinal splinting using an ileus tube under X-ray guidance. METHODS: Sixteen
      patients with recurrent postoperative adhesive small bowel obstruction (SBO)
      received internal splinting using intubation of a 300 cm long ileus tube. Under X
      ray guidance, the tube was advanced through nose, 10 cm beyond the jejunal
      ligament of Treitz. The tube was advanced towards the end of ileum and propelled
      by peristalsis using a water-filled anterior balloon of the tube, which directly
      dilated narrowed intestines. The tube remained in the intestine for further
      support and splinting. RESULTS: All 16 patients achieved a resolution of the
      bowel obstruction without complications. During a follow-up of 8 months to 2
      years, 1 patient had a recurrent obstruction 4 months post-procedure. The
      remaining patients did not experience obstruction recurrence. CONCLUSION: Non
      surgical, internal intestinal splinting using a nasointestinal ileus tube under X
      ray was simple, non-invasive, safe and effective treatment of recurrent adhesive
      SBO.

PMID- 25869261
TI  - A new vanadium sulfate with ferrimagnetic and NLO properties constructed from
      novel discrete umbrella-like [V(V)(MU3-O)4V(IV)4O5(SO4)4(en)]5- anions.
AB  - A new vanadium sulfate, [H2N(CH3)2](19/3)(en)[V5O5(MU3
      O)4(SO4)4](SO4)(2/3)[HN(CH3)2](2/3) 1, constructed from novel umbrella-like
      [V(V)(MU3-O)4V(IV)4O5(SO4)4(en)](5-) anions was synthesized and structurally
      characterized using single-crystal X-ray analysis. The magnetic and optical
      studies of 1 indicate that the title compound exhibits significant ZFS (zero
      field splitting), interesting ferrimagnetic interactions and strong two photon
      absorption.

PMID- 25869262
TI  - An approach to observational studies.

PMID- 25869264
TI  - Firearm fatalities in Western Sydney 1994-2003.
AB  - This study reviews firearm-related deaths (homicidal, suicidal and accidental)
      from 1994 to 2003 in the Western Sidney area, Australia, serviced by the Westmead
      Department of Forensic Medicine, in order to document the features of the cases
      and to assess the effect of the introduction of the NSW Firearms Act in 1996.
      There were 211 fatalities involving firearms (1.8% of all of the Coroner's cases
      for the period); firearm deaths were classified as homicide (75), suicide (134)
      or accidental (2). There was a clear peak of homicide deaths by firearm in the 20
      29 age group, whereas the suicide peak was broad, spanning the ages 20-69 years.
      More suicides occurred at home than homicides and a higher proportion of suicides
      were by rifle than homicides, which favoured hand guns. Entry wounds in suicides
      mostly involved the head, with the chest being the commonest entry site in
      homicides. The only statistically significant trend was for an increase in the
      number of firearm-related suicides in males, comparing the number of deaths pre-
      and post-firearm law introduction. The study includes reports of two suicides by
      unusual weapons: a home-made pipe gun and a spear gun. 

PMID- 25869265
TI  - Safety restraint injuries in fatal motor vehicle collisions.
AB  - The presence of an apparent seat belt mark (SBM) on a car crash occupant is often
      used as evidence for use of a seat belt at the time of the crash and, conversely,
      the lack of a SBM is used as an indication that no seat belt was used. This study
      examined whether there are clear indications of seat belt use to be found at
      autopsy and evaluated the sensitivity and specificity of apparent SBM and whether
      the use of a seat belt and seating location affects the type and severity of
      injuries sustained. Information on the type of injuries sustained and seatbelt
      use was retrieved from autopsy reports and police reports, respectively, for
      cases of fatal motor vehicle collisions occurring in Sydney, Australia over a 5
      year period. In this study, a SBM was only found on restrained occupants. The
      proportion of restrained occupants with evidence of a SBM was 36% (sensitivity),
      whilst unrestrained occupants showed no evidence of a SBM (100% specificity). A
      SBM was also found to reliably reflect the seating position of the occupant. We
      conclude that restrained occupants can be expected to show evidence of the seat
      belt in just over one third of cases and that the absence of a SBM is not
      necessarily an indication that no seat belt was used. Spurious SBM is very
      unlikely to be present if the occupant was unrestrained. 

PMID- 25869263
TI  - The science behind the quest to determine the age of bruises-a review of the
      English language literature.
AB  - Bruises are common injuries that can have medicolegal significance. There are
      those that maintain it is not possible to estimate the age of bruises. However,
      appreciation of the biological processes related to the resolution of a bruise
      suggests that these may provide information regarding the age of a bruise.
      Potential methods for determining the age of bruises-visual observation,
      colorimetry, spectrophotometry and histology-are reviewed. The observation of
      yellow (not orange or brown) indicates a bruise is not recent, but the abilities
      of visual observation are limited by the physiology of the human eye. Analysis of
      spectrophotometric data may provide more useful and objective information.
      Histological examination may be appropriate only in the postmortem situation. The
      lack of published information limits this as a tool for estimating the age of
      bruises. It is not known how the wide range of factors that can influence bruise
      formation and resolution could affect estimation of bruise age. 

PMID- 25869266
TI  - Performance verification of the Maxwell 16 Instrument and DNA IQ Reference Sample
      Kit for automated DNA extraction of known reference samples.
AB  - Advances in automation have been made for a number of processes conducted in the
      forensic DNA laboratory. However, because most robotic systems are designed for
      high-throughput laboratories batching large numbers of samples, smaller
      laboratories are left with a limited number of cost-effective options for
      employing automation. The Maxwell 16 Instrument and DNA IQ Reference Sample Kit
      marketed by Promega are designed for rapid, automated purification of DNA
      extracts from sample sets consisting of sixteen or fewer samples. Because the
      system is based on DNA capture by paramagnetic particles with maximum binding
      capacity, it is designed to generate extracts with yield consistency. The studies
      herein enabled evaluation of STR profile concordance, consistency of yield, and
      cross-contamination performance for the Maxwell 16 Instrument. Results indicate
      that the system performs suitably for streamlining the process of extracting
      known reference samples generally used for forensic DNA analysis and has many
      advantages in a small or moderate-sized laboratory environment. 

PMID- 25869267
TI  - "Lytic" lesions in autologous bone grafts: demonstration of medullary air pockets
      on post mortem computed tomography.
AB  - Donor bone grafts are an important aspect of orthopaedic surgery. The use of
      plain film as a pathological screening tool before donor bone dispatch has
      revealed "lytic" lesions in proximal humeri. Donor demographics did not support
      the diagnosis of myeloma and subsequent computed tomography (CT) scans of these
      bones identified the lesions as air, not pathology. In total, 27 long bones were
      scanned and 100% (27/27 cases) exhibited air within the trabecular bone. Three
      distinct patterns were found: ovoid, linear/branching, and broad channel. A
      longitudinal course of CT scans was performed to identify at which stage air
      appeared within the bone. Pre-retrieval, preprocessing, and postprocessing scans
      revealed that air originated between the retrieval and preprocessing stages of
      donor bone preparation. There may be multiple aetiology of this phenomenon,
      including bone retrieval and natural decomposition. 

PMID- 25869268
TI  - Poor reliability of facial indices for comparative metric facial identification
      without parametrical superimposition.
AB  - The relationship between the craniometric indices that can be evinced from the
      comparison of two faces for identification purposes is considered a reliable
      method for the personal identification of faces. Our study aims to assess whether
      facial indices are susceptible to substantial variations even if the two faces
      being compared are a different size, looking in a different direction, or
      differently angled. Our results showed high variability as regards both the
      facial indices thus obtained and the relative relations. This underlines the fact
      that regardless of the validity of the metric analysis method used, no numerical
      comparison can be reliable unless prior parametrical somato-physical
      superimposition of the images of the subjects has been performed to assess the
      complete comparability of the faces of the suspects. In conclusion, no reliable
      identification can be made with the simplified techniques that bypass this
      difficult, demanding and time-consuming phase of parametric superimposition, as
      we have shown that they can lead to gross errors. 

PMID- 25869269
TI  - A death due to concussive brain injury augmented by alcohol (case report).
AB  - We report here the case of a death following blunt trauma to the head in which
      the victim immediately became unconscious and remained unconscious until death.
      There were no associated intracranial bleeding or visible macroscopic/microscopic
      injuries to the brain. Additional injuries to other parts of the body included
      non-fatal contusions and abrasions. The victim was intoxicated, with a blood
      alcohol level of 168 mg/dl. Therefore, the conclusion was drawn that death in
      this case was due to the combination of the concussive effects of the head trauma
      and the central nervous system depressant effects of alcohol. 

PMID- 25869270
TI  - DNA reviews: the national DNA database of the United Kingdom.
AB  - The national DNA database in United Kingdom has now been operational for over 10
      years. This review looks at the history and development of this investigative
      resource. From the development of commercial DNA profiling kits to the current
      statistics for matches obtained in relation to criminal investigation in the
      United Kingdom, before moving onto discussing potential future direction that
      national DNA databases might take, including international collaboration on a
      European and global scale. 

PMID- 25869271
TI  - The use of magnetic resonance in the hospital and coronial pediatric postmortem
      examination.
AB  - The role of magnetic resonance imaging (MRI) has rapidly progressed from being a
      research tool to an ancillary pre-autopsy imaging technique and now an adjunct of
      the postmortem (PM) examination. In this review, we describe our experience with
      the use of PM MRI over the last 6 years in more than 300 fetal PM examinations,
      initially as research and finally the most recent use in 30 pediatric coronial
      autopsies. The pediatric pathologist and the neonatal and fetal radiologist
      retrospectively measured the impact on diagnosis at each stage of the development
      of the technique together. All imaging techniques have the advantage of being non
      invasive, more acceptable to the public, especially certain religious groups and
      provide a permanent record of the features observed. 

PMID- 25869272
TI  - Baalat 3.4.

PMID- 25869274
TI  - Floral advertisement and the competition for pollination services.
AB  - Flowering plants are a major component of terrestrial ecosystems, and most of
      them depend on animal pollinators for reproduction. Thus, the mutualism between
      flowering plants and their pollinators is a keystone ecological relationship in
      both natural and agricultural ecosystems. Though plant-pollinator interactions
      have received considerable amount of attention, there are still many unanswered
      questions. In this paper, we use methods of evolutionary game theory to
      investigate the co-evolution of floral advertisement and pollinator preferences
      Our results indicate that competition for pollination services among plant
      species can in some cases lead to specialization of the pollinator population to
      a single plant species (oligolecty). However, collecting pollen from multiple
      plants - at least at the population level - is evolutionarily stable under a
      wider parameter range. Finally, we show that, in the presence of pollinators,
      plants that optimize their investment in attracting vs. rewarding visiting
      pollinators outcompete plants that do not. 

PMID- 25869273
TI  - Efficacy of a glycine transporter 1 inhibitor TASP0315003 in animal models of
      cognitive dysfunction and negative symptoms of schizophrenia.
AB  - RATIONALE: Since the hypofunction of the N-methyl-D-aspartate (NMDA) receptor is
      known to be involved in the pathophysiology of schizophrenia, the enhancement of
      NMDA receptor function through glycine modulatory sites is expected to be a
      useful approach for the treatment of schizophrenia. OBJECTIVES: We investigated
      the efficacy of a glycine transporter 1 (GlyT1) inhibitor that potentiates NMDA
      receptor function by increasing synaptic glycine levels in animal models for
      cognitive dysfunction and negative symptoms, both of which are poorly managed by
      current antipsychotics. RESULTS: A newly synthesized GlyT1 inhibitor, 3-chloro-N
      {(S)-[3-(1-ethyl-1H-pyrazol-4-yl)phenyl][(2S)-piperidin-2-yl]methyl}-4
      (trifluoromethyl)pyridine-2-carboxamide (TASP0315003) significantly improved
      cognitive deficit induced by MK-801 in the object recognition test in rats.
      Likewise, TASP0315003 significantly improved MK-801 impaired cognition in the
      social recognition test in rats and also enhanced social memory in treatment
      naive rats. In addition, repeated phencyclidine (PCP) treatment reduced the
      social interaction of paired mice, which may reflect negative symptoms such as
      social withdrawal, and both acute and sub-chronic treatment with TASP0315003
      reversed the reduction in social interaction induced by PCP. Moreover,
      TASP0315003 additionally exhibited an antidepressant effect in the forced
      swimming test in rats. In contrast, TASP0315003 did not affect spontaneous
      locomotor activity or rotarod performance and did not induce catalepsy,
      indicating that TASP0315003 does not cause sedation or motor dysfunction, which
      is sometimes observed with the use of current antipsychotics. CONCLUSIONS: These
      results suggest that GlyT1 inhibitors including TASP0315003 may be useful for the
      treatment of cognitive dysfunction and the negative symptoms of schizophrenia
      without having undesirable central nervous system side effects.

PMID- 25869276
TI  - Defensive behaviors and prosencephalic neurogenesis in pigeons (Columba livia)
      are affected by environmental enrichment in adulthood.
AB  - Neurogenesis in the adult brain appears to be phylogenetically conserved across
      the animal kingdom. In pigeons and other adult non-oscine birds, immature neurons
      are observed in several prosencephalic areas, suggesting that neurogenesis may
      participate in the control of different behaviors. The mechanisms controlling
      neurogenesis and its relevance to defensive behaviors in non-oscine birds remain
      elusive. Herein, the contribution of the environment to behavior and neurogenesis
      of pigeons was investigated. Adult pigeons (Columba livia, n = 6/group), housed
      in standard (SE) or enriched environment (EE) for 42 days, were exposed to an
      unfamiliar environment (UE) followed by presentation to a novel object (NO).
      Video recordings of UE+NO tests were analyzed and scored for latency, duration
      and frequency of angular head movements, peeping, grooming, immobility and
      locomotion. Twenty-four hours later, pigeons were submitted to the tonic
      immobility test (TI) and number of trials for TI and TI duration were scored,
      followed by euthanasia 2 h later. Brains were immunohistochemically processed to
      reveal doublecortin (DCX), a marker for newborn neurons. Compared to those housed
      in SE, the pigeons housed in EE responded to a NO with more immobility. In
      addition, the pigeons housed in EE presented longer TI, more DCX-immunoreactive
      (DCX-ir) cells in the hippocampus and fewer DCX-ir cells in the lateral striatum
      than those housed in SE. There was no correlation between the number of DCX-ir
      cells and the scores of immobility in behavioral tests. Together, these data
      suggest that enrichment favored behavioral inhibition and neurogenesis in the
      adult pigeons through different, parallel mechanisms.

PMID- 25869275
TI  - Transgene expression in the Nop-tTA driver line is not inherently restricted to
      the entorhinal cortex.
AB  - The entorhinal cortex (EC) plays a central role in episodic memory and is among
      the earliest sites of neurodegeneration and neurofibrillary tangle formation in
      Alzheimer's disease. Given its importance in memory and dementia, the ability to
      selectively modulate gene expression or neuronal function in the EC is of
      widespread interest. To this end, several recent studies have taken advantage of
      a transgenic line in which the tetracycline transactivator (tTA) was placed under
      control of the neuropsin (Nop) promoter to limit transgene expression within the
      medial EC and pre-/parasubiculum. Although the utility of this driver is
      contingent on its spatial specificity, no detailed neuroanatomical analysis of
      its expression has yet been conducted. We therefore undertook a systematic
      analysis of Nop-tTA expression using a lacZ reporter and have made the complete
      set of histological sections available through the Rodent Brain Workbench tTA
      atlas, www.rbwb.org . Our findings confirm that the highest density of tTA
      expression is found in the EC and pre-/parasubiculum, but also reveal
      considerable expression in several other cortical areas. Promiscuous transgene
      expression may account for the appearance of pathological protein aggregates
      outside of the EC in mouse models of Alzheimer's disease using this driver, as we
      find considerable overlap between sites of delayed amyloid deposition and regions
      with sparse beta-galactosidase reporter labeling. While different tet-responsive
      lines can display individual expression characteristics, our results suggest
      caution when designing experiments that depend on precise localization of gene
      products controlled by the Nop-tTA or other spatially restrictive transgenic
      drivers.

PMID- 25869277
TI  - Beneficial effects of Ectothiorhodospira shaposhnikovii WF on larval cultivation
      of Litopenaeus vannamei.
AB  - To develop high quality probiotics for shrimp larviculture, the effects of a
      photosynthetic purple sulphur bacterium WF identified as Ectothiorhodospira
      shaposhnikovii on survival and development of Litopenaeus vannamei larvae were
      evaluated in vivo. The larvae exhibited a better survival rate after
      administration of strain WF compared to the probiotic Rhodopseudomonas palustris.
      To investigate the effect of dose and dosing frequency, strain WF was added to
      larvae, stages nauplius 6 to zoea 3, at three different doses and dosing
      frequencies. Larval treatment with strain WF twice at 10(6) cfu/ml exhibited
      significantly higher survival compared to the other doses and dosing frequencies
      as well as the control. The effect on water quality was assessed by applying
      strain WF to larvae, stages nauplius 6 to postlarvae 1, under conditions of zero
      water exchange and one-third water exchange. The larvae exhibited higher survival
      and faster growth when treated under conditions of zero water exchange. No
      significant difference was detected in the levels of three water quality
      parameters and in vibrio counts between these two conditions. Therefore, E.
      shaposhnikovii WF acts both as a bioremediation agent and nutrient source and can
      benefit shrimp larvae if given at an appropriate dose and dosing frequency.
      Strain WF, a moderate halophile, shows great promise as a water additive in
      improving water quality and providing nutrition for shrimp larviculture. 

PMID- 25869278
TI  - Amelioration of ovalbumin induced allergic symptoms in Balb/c mice by potentially
      probiotic strains of lactobacilli.
AB  - To evaluate the antiallergic effect of newly characterised probiotic strains,
      Lactobacillus fermentum NWS29, Lactobacillus casei NWP08 and Lactobacillus
      rhamnosus NWP13, mice were divided into six experimental groups: control,
      ovalbumin (OVA), NWS29, NWP08, NWP13 and L. rhamnosus GG (LGG). Mice were
      immunised and probiotics were administered via oral gavage followed by challenge
      with OVA. After last challenge with OVA, inflammatory cells in bronchoalveolar
      lavage fluid (BALF), recruitment of inflammatory cells in airways and OVA
      specific immunoglobulin E (IgE) in serum were determined by Giemsa, haematoxylin
      and eosin (HE) staining, and ELISA, respectively. Relative mRNA expression of
      interleukins (IL-4, IL-5, IL-10, IL-13 and IL-17), transforming growth factor
      beta (TGF-beta) and interferon-gamma (IFN-gamma) in lung and spleen tissue was
      determined by real time RT-PCR. OVA-specific IgE levels, recruitment of
      eosinophils and mRNA expressions of inflammatory cytokines were remarkably
      increased in OVA-exposed mice compared with the control group. Administration of
      NWS29 and NWP13 suppressed inflammatory cell infiltration in airways and BALF,
      and level of OVA-specific IgE in serum of OVA-exposed mice. Furthermore, NWS29
      and NWP13 also abrogated the mRNA expression of 1L-4, IL-5, IL-13 and TGF-beta in
      mice immunised and exposed to OVA. Our findings suggest that NWS29 and NWP13
      might be good candidates for the prevention of allergic airway inflammation. 

PMID- 25869279
TI  - Flow cytometry as an auxiliary tool for the selection of probiotic bacteria.
AB  - Selection of appropriate bacterial strains is crucial for development of new
      probiotic preparations. The fundamental prerequisite for potential efficacy of a
      probiotic preparation for oral application is the selection of appropriate
      bacterial strains with good gastrointestinal colonisation abilities,
      antimicrobial activity, and tolerance of conditions in the gastrointestinal
      tract, resistance to different antimicrobial agents, survival during processing
      and storage. The strain should be genetically stable, it should have good growth
      properties, to maintain its high viability at processing and when in storage.
      Mostly, the properties of promising strains are tested in the first phase in
      vitro, and only the best ones undergo subsequent in vivo testing. in vitro tests
      are often performed by classical microbiological cultivation methods which are
      material and time consuming, and they are not able to distinguish between 'viable
      but nonculturable' and dead bacteria. Flow cytometry is usually used for
      counting, phenotyping or functional characterisation of immune cells. Nowadays,
      flow cytometry is increasingly used in microbiology for counting bacteria,
      determining their viability and metabolic activity, detecting specific strains or
      testing their adherence abilities. The utilisation of flow cytometry in
      combination with an appropriate fluorescent labelling represents an effective and
      rapid method for the selection of probiotic bacteria. 

PMID- 25869280
TI  - Comparison of detection methods for vaginal lactobacilli.
AB  - Vaginal lactobacilli offer protection against microbiota imbalance and
      genitourinary tract infections. We compared vaginal lactobacilli in 50 Estonian
      women of child-bearing age applying culture-based methods, quantitative PCR and
      next-generation sequencing (NGS). The culture-based methods found three different
      lactobacilli: Lactobacillus crispatus, Lactobacillus jensenii and Lactobacillus
      gasseri. Using NGS revealed the presence of L. crispatus in 76%, Lactobacillus
      iners in 52%, L. jensenii in 47% and L. gasseri in 33% of the samples. According
      to qPCR, L. iners was present in 67% and L. crispatus in 64% of the samples. The
      proportions of L. crispatus revealed by qPCR and NGS were in good correlation
      (R=0.79, P<0.001), while that of L. iners correlated poorly (R=0.13, P>0.05).
      Good concordance for L. crispatus was also found between the results of the
      culture-based method and qPCR. Finally, good overlap between the results of the
      culture-based method and NGS was revealed: in case of a positive NGS result for
      L. crispatus, the same species was isolated in 95% of samples. The corresponding
      percentages were 82% for L. jensenii and 86% for L. gasseri. Our data indicate
      fairly general concordance of the three methods for detecting vaginal
      lactobacilli, except for L. iners. This points out the importance of
      standardisation of techniques, and the respective studies should involve cultures
      applying a medium suitable for the fastidious L. iners. 

PMID- 25869281
TI  - Lactobacillus fermentum NS9 restores the antibiotic induced physiological and
      psychological abnormalities in rats.
AB  - Gut microbiota play a vital role in maintaining the health of the host. Many
      factors affect gut microbiota; application of broad range antibiotics disturb
      microbiota, while probiotic application protects the microbiota. To investigate
      how probiotics alter the physiological and psychological changes induced by
      antibiotics, we tested the performance of ampicillin-treated rats in the presence
      or absence of Lactobacillus fermentum strain NS9, in elevated plus maze and
      Morris water maze. The results showed that NS9 normalised the composition of gut
      microbiota and alleviated the ampicillin-induced inflammation in the colon. The
      levels of the mineralocorticoid and N-methyl-D-aspartate receptors were also
      elevated in the hippocampus of the ampillicin+NS9 treated group. NS9
      administration also reduced the anxiety-like behaviour and alleviated the
      ampicillin-induced impairment in memory retention. These findings suggest that
      NS9 is beneficial to the host, because it restores the physiological and
      psychological abnormalities induced by ampicillin. Our results highlight how gut
      contents regulate the brain, and shed light on the clinical applications of
      probiotics to treat the side effect of antibiotics and mental disorders. 

PMID- 25869282
TI  - The effects of the multispecies probiotic mixture Ecologic(r)Barrier on migraine:
      results of an open-label pilot study.
AB  - Migraine prevalence is associated with gastrointestinal disorders. Possible
      underlying mechanisms could be increased gut permeability and inflammation.
      Probiotics may decrease intestinal permeability as well as inflammation, and
      therefore may reduce the frequency and/or intensity of migraine attacks.
      Therefore we assessed feasibility, possible clinical efficacy, and adverse
      reactions of probiotic treatment in migraine patients. 29 migraine patients took
      2 g/d of a probiotic food supplement (Ecologic((r))Barrier, 2.5*10(9) cfu/g)
      during 12 weeks. Participants recorded frequency and intensity of migraine in a
      headache diary and completed the Migraine Disability Assessment Scale (MIDAS) and
      Henry Ford Hospital Headache Disability Inventory (HDI) at baseline and after 12
      weeks of treatment. Compliance was measured every 4 weeks by counting the
      remaining sachets with probiotics. The study was completed by 27/29 (93%)
      patients who took 95% of the supplements. Obstipation was reported by 4 patients
      during the first 2 weeks of treatment only. The mean+/-standard deviation (SD)
      number of migraine days/month decreased significantly from 6.7+/-2.4 at baseline
      to 5.1+/-2.2 (P=0.008) in week 5-8 and 5.2+/-2.4 in week 9-12 (P=0.001). The
      mean+/-SD intensity of migraine decreased significantly from 6.3+/-1.5 at
      baseline to 5.5+/-1.9 after treatment (P=0.005). The MIDAS score improved from
      24.8+/-25.5 to 16.6+/-13.5 (P=0.031). However, the mean HDI did not change
      significantly. In conclusion, probiotics may decrease migraine supporting a
      possible role for the intestine in migraine management. Feasibility and lack of
      adverse reactions justify further placebo-controlled studies. 

PMID- 25869283
TI  - Strategies to develop strain-specific PCR based assays for probiotics.
AB  - Since health benefits conferred by probiotics are strain-specific, identification
      to the strain level is mandatory to allow the monitoring of the presence and the
      abundance of specific probiotic in a product or in a gastrointestinal tract.
      Compared to standard plate counts, the reduced duration of the assays and higher
      specificity makes PCR-based methods (standard PCR and quantitative PCR) very
      appropriate for detection or quantification of probiotics. Development of strain
      specific assay consists of 4 main stages: (1) strain-specific marker
      identification; (2) construction of potential strain-specific primers; (3)
      validation on DNA from pure cultures of target and related strains; and (4)
      validation on spiked samples. The most important and also the most challenging
      step is the identification of strain-specific sequences, which can be
      subsequently targeted by specific primers or probes. Such regions can be
      identified on sequences derived from 16S-23S internally transcribed spacers,
      randomly amplified polymorphic DNA, representational difference analysis and
      suppression subtractive hybridisation. Already known phenotypic or genotypic
      characteristics of the target strain can also be used to develop the strain
      specific assay. However, the initial stage of strain-specific assay development
      can be replaced by comparative genomics analysis of target genome with related
      genomes in public databases. Advances in whole genome sequencing (WGS) have
      resulted in a cost reduction for bacterial genome sequencing and consequently
      have made this approach available to most laboratories. In the present paper I
      reviewed the available literature on PCR and qPCR assays developed for detection
      of a specific probiotic strain and discussed future WGS and comparative genomics
      based approaches. 

PMID- 25869285
TI  - The biology and management of systemic anaplastic large cell lymphoma.
AB  - Systemic anaplastic large cell lymphoma (ALCL) is an aggressive CD30(+) non
      Hodgkin lymphoma. Anaplastic lymphoma kinase-positive (ALK+) ALCL is associated
      with the NPM-ALK t(2;5) translocation, which is highly correlated with the
      identification of the ALK protein by immunohistochemistry. ALK+ ALCL typically
      occurs in younger patients and has a more favorable prognosis with 5-year
      survival rates of 70% to 90% in comparison with 40% to 60% for ALK-negative (ALK
      ) ALCL. Studies support young age as a strong component of the favorable
      prognosis of ALK+ ALCL. Until recently, no recurrent translocations were
      identified in ALK- ALCL. However, emerging data now highlight that ALK- ALCL is
      genetically and clinically heterogeneous with a subset having either a DUSP22
      translocation and a survival rate similar to ALK+ ALCL or a less common P63
      translocation, the latter associated with an aggressive course. Anthracycline
      based regimens such as cyclophosphamide, doxorubicin, vincristine, and prednisone
      (CHOP) remain the standard first-line treatment choice for systemic ALCL, but in
      many patients with ALK- ALCL, it is ineffective, and thus it is often followed by
      consolidative autologous stem cell transplantation. However, selection of
      appropriate patients for intensified therapy remains challenging, particularly in
      light of genetic and clinical heterogeneity in addition to the emergence of new,
      effective therapies. The antibody drug conjugate brentuximab vedotin is
      associated with a high response rate (86%) and durable remissions in
      relapsed/refractory ALCL and is under investigation in the first-line setting. In
      the future, combining clinical and genetic biomarkers may aid in risk
      stratification and help guide initial patient management. 

PMID- 25869284
TI  - Clinical and pharmacodynamic analysis of pomalidomide dosing strategies in
      myeloma: impact of immune activation and cereblon targets.
AB  - In preclinical studies, pomalidomide mediated both direct antitumor effects and
      immune activation by binding cereblon. However, the impact of drug-induced immune
      activation and cereblon/ikaros in antitumor effects of pomalidomide in vivo is
      unknown. Here we evaluated the clinical and pharmacodynamic effects of continuous
      or intermittent dosing strategies of pomalidomide/dexamethasone in lenalidomide
      refractory myeloma in a randomized trial. Intermittent dosing led to greater
      tumor reduction at the cost of more frequent adverse events. Both cohorts
      experienced similar event-free and overall survival. Both regimens led to a
      distinct pattern but similar degree of mid-cycle immune activation, manifested as
      increased expression of cytokines and lytic genes in T and natural killer (NK)
      cells. Pomalidomide induced poly-functional T-cell activation, with increased
      proportion of coinhibitory receptor BTLA(+) T cells and Tim-3(+) NK cells.
      Baseline levels of ikaros and aiolos protein in tumor cells did not correlate
      with response or survival. Pomalidomide led to rapid decline in Ikaros in T and
      NK cells in vivo, and therapy-induced activation of CD8(+) T cells correlated
      with clinical response. These data demonstrate that pomalidomide leads to strong
      and rapid immunomodulatory effects involving both innate and adaptive immunity,
      even in heavily pretreated multiple myeloma, which correlates with clinical
      antitumor effects. This trial was registered at www.clinicaltrials.gov as
      #NCT01319422. 

PMID- 25869287
TI  - Faster T-cell development following gene therapy compared with haploidentical
      HSCT in the treatment of SCID-X1.
AB  - During the last decade, gene therapy via ex vivo gene transfer into autologous
      hematopoietic stem cells has emerged as a convincing therapy for severe combined
      immunodeficiency caused by ILR2G mutation (SCID-X1) despite the occurrence of
      genotoxicity caused by the integration of first-generation retroviral vectors.
      However, the place of gene therapy among the therapeutic armamentarium remains to
      be defined. We retrospectively analyze and compare clinical outcomes and immune
      reconstitution in 13 consecutive SCID-X1 patients having undergone haploidentical
      hematopoietic stem cell transplantation (HSCT) and 14 SCID-X1 patients treated
      with gene therapy over the same period at a single center level: the Necker
      Children's Hospital (Paris, France). Our results show a clear advantage in terms
      of T-cell development of gene therapy over HSCT with a mismatched donor. Patients
      treated with gene therapy display a faster T-cell reconstitution and a better
      long-term thymic output. Interestingly, this advantage of gene therapy vs
      haploidentical HSCT seems to be independent of the existence of clinical graft
      versus-host disease in the latter condition. If data of safety are confirmed over
      the long term, gene therapy for SCID-X1 appears to be an equal, if not superior,
      alternative to haploidentical HSCT. 

PMID- 25869286
TI  - alpha-Globin as a molecular target in the treatment of beta-thalassemia.
AB  - The thalassemias, together with sickle cell anemia and its variants, are the
      world's most common form of inherited anemia, and in economically undeveloped
      countries, they still account for tens of thousands of premature deaths every
      year. In developed countries, treatment of thalassemia is also still far from
      ideal, requiring lifelong transfusion or allogeneic bone marrow transplantation.
      Clinical and molecular genetic studies over the course of the last 50 years have
      demonstrated how coinheritance of modifier genes, which alter the balance of
      alpha-like and beta-like globin gene expression, may transform severe,
      transfusion-dependent thalassemia into relatively mild forms of anemia. Most
      attention has been paid to pathways that increase gamma-globin expression, and
      hence the production of fetal hemoglobin. Here we review the evidence that
      reduction of alpha-globin expression may provide an equally plausible approach to
      ameliorating clinically severe forms of beta-thalassemia, and in particular, the
      very common subgroup of patients with hemoglobin E beta-thalassemia that makes up
      approximately half of all patients born each year with severe beta-thalassemia. 

PMID- 25869288
TI  - Initial assessment of rehabilitation needs using the WHODAS 2.0 in Estonia.
AB  - PURPOSE: Given the growing number of people with disabilities in Estonia, an
      initial rehabilitation needs assessment instrument that included the World Health
      Organization Disability Assessment Schedule (WHODAS 2.0) was developed and tested
      to determine its feasibility in assessing social rehabilitation needs. METHOD:
      WHODAS 2.0 items were complemented with questions about the nature of disability
      related problems with regard to personal, social and environmental aspects of
      functioning. Four rehabilitation specialists assessed 101 persons' needs in face
      to-face interviews. Data were analyzed using descriptive statistics and thematic
      analysis. RESULTS: The comprehensive initial assessment instrument tested was
      sufficiently informative to assess functioning and identify social rehabilitation
      and other social needs. Participants had difficulty in understanding some WHODAS
      2.0 items, and coding and scoring respondents' answers using WHODAS 2.0 frames of
      reference proved challenging for interviewers. CONCLUSION: The WHODAS 2.0 is
      mainly related to health conditions. Complementing it with questions about the
      nature and severity of the difficulties social rehabilitation service applicants
      experienced added essential information for planning interventions. IMPLICATIONS
      FOR REHABILITATION: A well conceived, holistic initial assessment that addresses
      biological, psychological, sociocultural and environmental factors can provide
      substantial information for targeting services to meet a person's rehabilitation
      needs. The WHODAS 2.0 is a useful framework for conducting initial assessments,
      but since it focuses on health needs, supplementing it with additional items
      about personal, social and environmental factors may be necessary to address
      services needs from social, vocational and other rehabilitation perspectives.
      Rehabilitation specialists must be well prepared to use the WHODAS 2.0 and
      conduct the overall assessment, including providing clear instructions and
      support to applicants applying for services.

PMID- 25869289
TI  - How does injury compensation affect health and disability in patients with
      complaints of whiplash? A qualitative study among rehabilitation experts
      professionals.
AB  - PURPOSE: To explore rehabilitation professionals' opinions about the influence
      and the pathways of injury compensation (IC) on health and disability in patients
      with whiplash associated disorder (WAD). METHODS: Semi-structured interviews were
      performed among a purposeful selected sample of Dutch expert-professionals in the
      field of rehabilitation of patients with WAD. Inclusion continued until
      saturation was reached. Inductive and deductive thematic analyses were performed.
      RESULTS: Ten rehabilitation expert-professionals (five females), working as
      physician, psychologist or physiotherapist, were interviewed. All expert
      professionals acknowledged that IC can influence rehabilitation, health and
      disability. The expert-professionals provided three causal pathways; a pathway
      through prolonged distress, a behavioral pathway, and patient characteristics
      that may either attenuate or worsen their response. They assess the influence of
      IC mainly with interview techniques. Most professionals discuss the potential
      influence of IC with their patients, because they want to give clear information
      to the patient. Some emphasize that their role is neutral in relation with the
      IC. Others mention that financial consequences can accompany functional
      improvement. CONCLUSIONS: Rehabilitation expert-professionals believe that IC may
      affect rehabilitation, health and disability in patients with WAD. Three pathways
      are mentioned by the experts-professionals. IMPLICATIONS FOR REHABILITATION:
      According to rehabilitation expert-professionals, an injury compensation (IC) can
      lead to distress, by creating a (conscious or unconscious) conflict of interests
      within a patient between striving for compensation on one hand, and recovery on
      the other hand. Patient characteristics can either attenuate or worsen IC-related
      distress. Reliable and valid tools need to be developed to assess the influence
      of IC on health, disability and rehabilitation, and to limit the negative
      effects. Rehabilitation professionals can discuss the possible unintended effects
      of IC with their patients to clarify their current situation.

PMID- 25869290
TI  - Prolonged grief symptoms related to loss of physical functioning: examining
      unique associations with medical service utilization.
AB  - PURPOSE: Prolonged grief, a severe and chronic form of grieving most commonly
      studied in the context of bereavement, may have relevance to losses associated
      with chronic illness (e.g. grief related to loss of functioning or loss of a
      planned future). The purpose of the present study is to examine the unique
      associations between prolonged grief symptoms and service utilization patterns.
      METHODS: An online self-report assessment battery was administered among a sample
      of 275 older adults with at least one chronic illness that caused significant
      physical impairment. RESULTS: Even after statistically controlling for relevant
      physical health (e.g. severity of physical limitations, somatic symptoms, number
      of chronic illnesses) and psychosocial variables (e.g. social support,
      depression/anxiety), more severe prolonged grief symptoms were associated with a
      greater number of emergency room visits, overnight stays in the hospital and
      total nights in the hospital. CONCLUSIONS: These findings highlight the
      importance of screening for prolonged grief symptomatology with older individuals
      with a debilitating chronic illness. IMPLICATIONS FOR REHABILITATION: Recent
      evidence suggests that prolonged grief may have relevance for losses associated
      with physical illness. The present study shows that prolonged grief reactions
      related to physical illness (e.g. grieving the loss of functioning) are uniquely
      associated with increased hospital-based service utilization. Given the relevance
      of prolonged grief reactions in this population, practitioners may wish to assess
      for these symptoms. Future clinical research should focus on developing
      interventions to target prolonged grief symptoms associated with these losses.

PMID- 25869291
TI  - Environmental risk factors and hotspot analysis of dengue distribution in
      Pakistan.
AB  - This study is an attempt to find out the factors responsible for sudden dengue
      outbreak in different cities of Pakistan during 2011. For this purpose, spatio
      temporal distribution of dengue in Islamabad, Rawalpindi, Lahore, and Karachi has
      been taken into account. According to the available data, the factors responsible
      for this spread includes climate covariates like rainfall, temperature, and wind
      speed; social covariates like population, and area of locality, and environmental
      risk factors like drainage pattern and geo-hydrological conditions. Reported
      dengue cases from localities and Shuttle Radar Topography Mission (SRTM) 90 m
      digital elevation model (DEM) of study areas have been processed for hotspots,
      regression model and stream density in the localities of high dengue incidence.
      The relationship of daily dengue incidence with climate covariates during the
      months of July-October of the study year is analyzed. Results show that each dry
      spell of 2-4 days provides suitable conditions for the development and survival
      of dengue vectors during the wet months of July and August in the areas of high
      stream density and population. Very few cases have been reported in July while
      higher number of cases reported in the months of August, September, until late
      October. Hotspot analysis highlights the areas of high dengue incidence while
      regression analysis shows the relationship between the population and the areas
      of localities with the dengue incidence.

PMID- 25869292
TI  - Ameliorative efficacy of tetrahydrocurcumin against arsenic induced oxidative
      damage, dyslipidemia and hepatic mitochondrial toxicity in rats.
AB  - Arsenic (As) is a well-known human carcinogen and a potent hepatotoxin.
      Environmental exposure to arsenic imposes a serious health hazard to humans and
      other animals worldwide. Tetrahydrocurcumin (THC), one of the major metabolites
      of curcumin, exhibits many of the same physiological and pharmacological
      activities as curcumin and in some systems may exert greater antioxidant activity
      than the curcumin. It has been reported that THC has antioxidant efficacy
      attributable to the presence of identical beta-diketone of 3rd and 5th
      substitution in heptane moiety. In the present study, rats were orally treated
      with arsenic alone (5 mg kg(-1) bw/day) with THC (80 mg kg(-1) bw/day) for 28
      days. Hepatotoxicity was measured by the increased activities of serum
      hepatospecific enzymes, namely aspartate transaminase, alanine transaminase,
      alkaline phosphatase and bilirubin along with increased elevation of lipid
      peroxidative markers, thiobarbituric acid reactive substances. And also elevated
      levels of serum cholesterol, triglycerides, free fatty acids and phospholipids
      were observed in arsenic intoxicated rats. These effects of arsenic were coupled
      with enhanced mitochondrial swelling, inhibition of cytochrome c oxidase,
      Ca(2+)ATPase and a decrease in mitochondrial calcium content. The toxic effect of
      arsenic was also indicated by significantly decreased activities of enzymatic
      antioxidants such as superoxide dismutase, catalase, and glutathione peroxidase
      along with non-enzymatic antioxidant such as reduced glutathione. Administration
      of THC exhibited significant reversal of arsenic induced toxicity in hepatic
      tissue. All these changes were supported by the reduction of arsenic
      concentration and histopathological observations of the liver. These results
      suggest that THC has a protective effect over arsenic induced toxicity in rat.

PMID- 25869294
TI  - Expression, Purification and Characterisation of Secreted Esterase Rv2525c from
      Mycobacterium tuberculosis.
AB  - Rv2525c from Mycobacterium tuberculosis belongs to the domain of unknown function
      (DUF) 1906 superfamily, but it also contains the motif G-X-S-X-G, the consensus
      active site sequence of the ester/lipid family. Biochemical analysis indicated
      that the mature Rv2525c protein is secreted. The discovery and characterisation
      of novel enzymes secreted by M. tuberculosis are vital for understanding the
      pathogenesis of the most important human bacterial pathogen. The proteome of M.
      tuberculosis contains over 400 potentially secreted proteins, of which the
      majority remain uncharacterised. In this study, we cloned and expressed the
      rv2525c gene in Escherichia coli and purified the recombinant protein using a
      three-step process (affinity chromatography, ion exchange chromatography, gel
      filtration chromatography), obtaining more than 99% pure protein. Mass
      spectrometry was performed to confirm that the purified protein was Rv2525c.
      Circular dichroism spectroscopy results showed that its conformation was stable
      at pH ranging from 6.0 to 8.0 and at temperatures <= 40  degrees C. Moreover, we
      tested the esterase activity using p-nitrophenyl esters (C2, C4, C6, C8, C12,
      C14, C16). This enzyme exhibited broad substrate acceptance, preferentially
      hydrolysing p-nitrophenyl butyrate (C4) at pH 7.0 and 37  degrees C. The dynamic
      activity test demonstrated that the optimal conditions were pH 8.0 and 38 
      degrees C. Site-directed mutagenesis studies revealed that Gly 113, Ser 115 and
      Gly 117 residues play catalytic roles in Rv2525c.

PMID- 25869293
TI  - [Need for the role of the patient's family members at the intensive care unit].
AB  - AIM: To know the current status for the role of family members in the intensive
      care unit and its evolution, analyzing areas for improvement and learning about
      the nursing role. METHODS: This work is a literature review. The selected
      articles included two of the key words in their title. Articles before year 2000
      were excluded, except some work of great interest. RESULTS: Family members lose
      their role and suffer a crisis when one of them is at the intensive care unit.
      Their normal role into the family changes or disappears. Obtaining a
      participation role increases satisfaction and decreases anxiety in relatives.
      Nursing professionals are essential in addressing this need. CONCLUSIONS: Solving
      the need for this role decreases anxiety and stress on relatives and patients.
      Their implication on the patient process enhances and helps professionals to know
      the patient's background.

PMID- 25869295
TI  - Mutations in Recombination Activating Gene 1 and 2 in patients with severe
      combined immunodeficiency disorders in Egypt.
AB  - The Recombination Activating Genes (RAG) 1/2 are important for the development
      and function of T and B cells. Loss of RAG1/2 function results in severe combined
      immunodeficiency (SCID), which could lead to early death. We studied the
      prevalence of RAG1/2 mutations in ten SCID patients in Egypt. We identified two
      novel homozygous nonsense mutations in RAG1, a novel homozygous deletion, and a
      previously reported homozygous missense mutation from four patients, as well as
      two homozygous mutations in RAG2 from the same patient. Prenatal diagnosis
      performed in the mother of a patient with RAG1 deficiency determined that the
      fetus was heterozygous for the same mutation. This represents the first report on
      RAG1/2 mutations in SCID patients in Egypt. The early diagnosis dramatically
      affects the outcome of the disease by allowing bone marrow transplantation at an
      early age, and providing prenatal diagnosis and genetic counseling for families
      with a history of SCID. 

PMID- 25869296
TI  - Macromolecular glucocorticoid prodrug improves the treatment of dextran sulfate
      sodium-induced mice ulcerative colitis.
AB  - A macromolecular prodrug (P-Dex) of dexamethasone (Dex) was developed to improve
      the treatment of inflammatory bowel disease (IBD). Colonic inflammation was
      induced by feeding mice with dextran sulfate sodium. Mice were treated with daily
      i.p. injection of free Dex or single i.v. injection of P-Dex, PBS or free
      polymer. Both P-Dex and free Dex could lower disease activity index and histology
      scores when compared to the controls. A single injection of P-Dex with 1/4
      equivalent Dex dose had a better therapeutic effect than daily free Dex
      treatment. Mechanism study found that P-Dex could target the inflamed colon, and
      be retained by epithelial cells and local inflammatory infiltrates, suggesting
      that the improved efficacy of P-Dex may be attributed to its inflammation
      targeting, subcellular processing and activation. Collectively, these data
      support our hypothesis that the development of macromolecular prodrug of
      glucocorticoid may have the potential to improve the clinical management of IBD. 

PMID- 25869297
TI  - The cation channel Trpv2 is a new suppressor of arthritis severity, joint damage,
      and synovial fibroblast invasion.
AB  - Little is known about the regulation of arthritis severity and joint damage in
      rheumatoid arthritis (RA). Fibroblast-like synoviocytes (FLS) have a central role
      in joint damage and express increased levels of the cation channel Trpv2. We
      aimed at determining the role of Trpv2 in arthritis. Treatment with Trpv2
      specific agonists decreased the in vitro invasiveness of FLS from RA patients and
      arthritic rats and mice. Trpv2 stimulation suppressed IL-1beta-induced expression
      of MMP-2 and MMP-3. Trpv2 agonists, including the new and more potent LER13,
      significantly reduced disease severity in KRN serum- and collagen-induced
      arthritis, and reduced histologic joint damage, synovial inflammation, and
      synovial blood vessel numbers suggesting anti-angiogenic activity. In this first
      in vivo use of Trpv2 agonists we discovered a new central role for Trpv2 in
      arthritis. These new compounds have the potential to become new therapies for RA
      and other diseases associated with inflammation, invasion, and angiogenesis. 

PMID- 25869298
TI  - Signal transducer and activator of transcription (STAT) 3 inhibition delays the
      onset of lupus nephritis in MRL/lpr mice.
AB  - The transcription factor STAT3 is overexpressed and hyperactivated in T cells
      from SLE patients. STAT3 plays a central role in T cell differentiation into Th17
      and T follicular helper cells, two subsets that orchestrate autoimmune responses
      in SLE. Moreover, STAT3 is important in chemokine-mediated T cell migration. To
      better understand its role in SLE, we inhibited STAT3 in lupus-prone mice using
      the small molecule Stattic. Stattic-treated mice exhibited delayed onset of
      proteinuria (3 weeks later than controls), and had lower levels of anti-dsDNA
      antibodies and inflammatory cytokines. Inhibitor treatment reduced
      lymphadenopathy, resulted in a 3-fold decrease in total T cell number, and a 4
      fold decrease in the numbers of T follicular helper cells. In vitro experiments
      showed that Stattic-treated T cells exhibited decreased proliferation and a
      decrease in ability to migrate to CXCL12. We propose that STAT3 inhibition
      represents a therapeutic target in SLE, particularly lupus nephritis.

PMID- 25869299
TI  - Amelioration of allergic airway inflammation in mice by regulatory IL-35 through
      dampening inflammatory dendritic cells.
AB  - BACKGROUND: IL-35, a new member of the IL-12 family, is an inhibitory cytokine
      produced by regulatory T and B lymphocytes that play a suppressive role in the
      inflammatory diseases. This study focuses on the cellular mechanism regulating
      the anti-inflammatory activity of IL-35 in asthmatic mice. METHODS: Ovalbumin
      induced asthmatic and humanized asthmatic mice were adopted to evaluate the in
      vivo anti-inflammatory activities of IL-35. For monitoring the airway, Penh value
      (% baseline) was measured using a whole-body plethysmograph. RESULTS: In this
      study using ovalbumin-induced asthmatic mice, we observed that intraperitoneal
      injection of IL-35 during the allergen sensitization stage was more efficient
      than administration in the challenge stage for the amelioration of airway hyper
      responsiveness. This was reflected by the significantly reduced concentration of
      asthma-related Th2 cytokines IL-5 and IL-13, as well as eosinophil counts in
      bronchoalveolar lavage fluid (all P < 0.05). IL-35 also significantly attenuated
      the accumulation of migratory CD11b+CD103(-) dendritic cells (DC) in the
      mediastinal lymph node (mLN) and lung of mice (all P < 0.05). IL-35 markedly
      inhibited the ovalbumin-induced conversion of recruited monocytes into
      inflammatory DC, which were then substantially reduced in mLN to cause less T
      cell proliferation (all P < 0.05). Further study using the humanized asthmatic
      murine model also indicated human IL-35 exhibited a regulatory impact on allergic
      asthma. CONCLUSION: Our findings suggest that IL-35 can act as a crucial
      regulatory cytokine to inhibit the development of allergic airway inflammation
      via suppressing the formation of inflammatory DC at the inflammatory site and
      their accumulation in the draining lymph nodes.

PMID- 25869300
TI  - Enhancing nurses' empowerment: the role of supervisors' empowering management
      practices.
AB  - AIM: This study tests a theoretical model where: (a) nurses' dispositional
      resistance to change is indirectly negatively related to behavioural empowerment
      through the mediating role of psychological empowerment; and (b) supervisors'
      empowering management practices buffer both the negative relationship between
      dispositional resistance to change and psychological empowerment and the indirect
      negative relationship between resistance to change and behavioural empowerment
      via psychological empowerment. BACKGROUND: Promoting a high level of empowerment
      among nursing personnel is important to ensure their effectiveness in the context
      of organizational change. It is thus essential to advance our current
      understanding of the factors that hamper nurses' psychological and behavioural
      expressions of empowerment and to clarify supervisor practices that can overcome
      such barriers. DESIGN: A cross-sectional research design. METHOD: We collected
      survey data during 2012 from a sample of 197 nurses from a Canadian hospital
      undergoing a major organizational change. RESULTS: Results from moderated
      mediation analyses provided evidence for an indirect negative relationship
      between dispositional resistance to change and behavioural empowerment through
      psychological empowerment, and for a moderating (buffering) effect of
      supervisors' empowering management practices on this mediated relationship. These
      findings provided support for our hypotheses. CONCLUSIONS: Supervisors'
      empowering management practices represent an important contextual buffer against
      the negative effects of dispositional resistance to change on nurses'
      empowerment. Organizations should develop empowering management skills among
      nurses' supervisors to counteract the detrimental effects of dispositional
      resistance to change and to sustain an empowered nursing workforce.

PMID- 25869301
TI  - Insulin-secreting adipose-derived mesenchymal stromal cells with bone marrow
      derived hematopoietic stem cells from autologous and allogenic sources for type 1
      diabetes mellitus.
AB  - BACKGROUND AIMS: Stem cell therapy (SCT) is now the up-coming therapeutic
      modality for treatment of type 1 diabetes mellitus (T1DM). METHODS: Our study was
      a prospective, open-labeled, two-armed trial for 10 T1DM patients in each arm of
      allogenic and autologous adipose-derived insulin-secreting mesenchymal stromal
      cells (IS-AD-MSC)+bone marrow-derived hematopoietic stem cell (BM-HSC) infusion.
      Group 1 received autologous SCT: nine male patients and one female patient; mean
      age, 20.2 years, disease duration 8.1 years; group 2 received allogenic SCT: six
      male patients and four female patients, mean age, 19.7 years and disease
      duration, 7.9 years. Glycosylated hemoglobin (HbA1c) was 10.99%; serum (S.) C
      peptide, 0.22 ng/mL and insulin requirement, 63.9 IU/day in group 1; HbA1c was
      11.93%, S.C-peptide, 0.028 ng/mL and insulin requirement, 57.55 IU/day in group
      2. SCs were infused into the portal+thymic circulation and subcutaneous tissue
      under non-myelo-ablative conditioning. Patients were monitored for blood sugar,
      S.C-peptide, glutamic acid decarboxylase antibodies and HbA1c at 3-month
      intervals. RESULTS: Group 1 received mean SCs 103.14 mL with 2.65 +/- 0.8 * 10(4)
      ISCs/kg body wt, CD34+ 0.81% and CD45-/90+/73+, 81.55%. Group 2 received mean SCs
      95.33 mL with 2.07 +/- 0.67 * 10(4) ISCs/kg body wt, CD34+ 0.32% and CD45
      /90+/73+ 54.04%. No untoward effect was observed with sustained improvement in
      HbA1c and S.C-peptide in both groups with a decrease in glutamic acid
      decarboxylase antibodies and reduction in mean insulin requirement. CONCLUSIONS:
      SCT is a safe and viable treatment option for T1DM. Autologous IS-AD-MSC+ BM-HSC
      co-infusion offers better long-term control of hyperglycemia as compared with
      allogenic SCT.

PMID- 25869302
TI  - Delay-specific stimuli and genotype interact to determine temporal discounting in
      a rapid-acquisition procedure.
AB  - The importance of delay discounting to many socially important behavior problems
      has stimulated investigations of biological and environmental mechanisms
      responsible for variations in the form of the discount function. The extant
      experimental research, however, has yielded disparate results, raising important
      questions regarding Gene X Environment interactions. The present study determined
      the influence of stimuli that uniquely signal delays to reinforcement on delay
      discounting in two inbred mouse strains using a rapid-acquisition procedure.
      BALB/c and C57BL/6 mice responded under a six-component, concurrent-chained
      schedule in which the terminal-link delays preceding the larger-reinforcer were
      presented randomly across components of an individual session. Across conditions,
      components were presented either with or without delay-specific auditory stimuli,
      i.e., as multiple or mixed schedules. A generalized matching-based model was used
      to incorporate the impact of current and previous component reinforcer-delay
      ratios on current component response allocation. Sensitivity to reinforcer
      magnitude and delay were higher for BALB/c mice, but within-component preference
      reached final levels faster for C57Bl/6 mice. For BALB/c mice, acquisition of
      preference across blocks of a component was faster under the multiple than the
      mixed schedule, but final levels of sensitivity to reinforcement were unaffected
      by schedule. The speed of acquisition of preference was not different across
      schedules for C57Bl/6 mice, but sensitivity to reinforcement was higher under the
      multiple than the mixed schedule. Overall, differences in the acquisition and
      final form of the discount function were determined by a Gene X Environment
      interaction, but the presence of delay-specific stimuli attenuated genotype
      dependent differences in magnitude and delay sensitivity. 

PMID- 25869304
TI  - The Association of Investment Model Variables and Dyadic Patterns of Physical
      Partner Violence: A Study of College Women.
AB  - Previous research has examined the association between intimate partner violence
      (IPV) victimization experiences and investment model variables, particularly with
      relation to leaving intentions. However, research only has begun to explore the
      impact that various dyadic patterns of IPV (i.e., unidirectional victimization,
      unidirectional perpetration, bidirectional violence, and non-violence) have on
      investment model variables. Grounded in behavioral principles, the current study
      used a sample of college women to assess the impact that perpetration and
      victimization have on investment model variables. Results indicated that 69.2% of
      the sample was in a relationship with no IPV. Among those who reported IPV in
      their relationships, 11.9% reported unidirectional perpetration, 10.6%
      bidirectional violence, and 7.4% unidirectional victimization. Overall, the
      findings suggest that women's victimization (i.e., victim only and bidirectional
      IPV) is associated with lower levels of satisfaction and commitment, and that
      women's perpetration (i.e., perpetration only and bidirectional IPV) is
      associated with higher levels of investment. Women in bidirectionally violent
      relationships reported higher quality alternatives than women in non-violent
      relationships. The current study emphasizes the importance of considering both
      IPV perpetration and IPV victimization experiences when exploring women's
      decisions to remain in relationships.

PMID- 25869305
TI  - Artificial receptors for nitrate: a comprehensive overview.
AB  - This feature article highlights recent developments in the field of synthetic
      receptors designed to recognize nitrate with a particular emphasis on: (i)
      synthetic receptors for nitrate in competitive media, (ii) assembly processes
      driven by nitrate recognition and (iii) synthetic transporters and extractants
      for nitrate. 

PMID- 25869303
TI  - Chronic angiotensin AT2R activation prevents high-fat diet-induced adiposity and
      obesity in female mice independent of estrogen.
AB  - OBJECTIVE: Obesity is a known risk factor for various metabolic disorders and
      cardiovascular diseases. Recently we demonstrated that female angiotensin AT2
      receptor (AT2R) knockout mice on high-fat diet (HFD) had higher body weight and
      adiposity with a parallel reduction in estrogen (17,beta-estradiol/E2). The
      present study investigated whether the anti-adiposity effects of the AT2R are
      estrogen-dependent in female mice. METHODS: Female C57BL/6 ovary-intact (Ovi)
      mice were treated with an AT2R agonist (C21, 0.3 mg/kg, daily i.p.).
      Ovariectomized (Ovx) mice, supplemented with E2 (5 MUg/day, pellets implanted
      subcutaneously), were treated with an AT2R agonist (C21, 0.3 mg/kg, daily i.p.)
      or vehicle. After 4-days of pre-treatment with C21, Ovi and Ovx mice were placed
      on either normal diet (ND) or HFD while the C21 treatment continued for the next
      10 days. For a long-term study, Ovi mice were placed on HFD and treated with C21
      for 12 weeks. RESULTS: Ovi mice fed the HFD had increased parametrial white
      adipose tissue (pWAT) weight, plasma free fatty acid and triglycerides compared
      to Ovi mice on ND. Ovariectomy alone caused similar changes in these parameters
      which were further increased by HFD-feeding. C21 treatment attenuated these HFD
      induced changes in Ovi as well as Ovx mice. HFD also, increased the liver/body
      weight ratio and decreased the liver expression of the beta-oxidation enzyme,
      carnitine palmitoyltransferase 1 (CPT1-A). C21 treatment attenuated these changes
      as well. The long-term C21 treatment of Ovi mice lowered the HFD-induced body
      weight gain, increase in pWAT weight, parametrial adipocyte size and
      hyperinsulinemia induced by HFD. Finally, HFD drastically reduced urinary
      estrogen and the beneficial metabolic changes in response to C21-treatment
      occurred without significantly increasing urinary estrogen. CONCLUSION: We
      suggest that the pharmacological activation of AT2R by the agonist C21 reduces
      adiposity and body weight gain independent of estrogen in female mice.
      Improvement in fatty acid metabolism is a potential mechanism by which the AT2R
      exerts anti-adiposity effects.

PMID- 25869306
TI  - Mid-term Results of Oxford Phase 3 Unicompartmental Knee Arthroplasties at a
      Small-Volume Center.
AB  - BACKGROUND AND AIMS: Unicompartmental knee arthroplasty is considered as an
      alternative to total knee arthroplasty for patients who have osteoarthritis
      limited to the medial compartment of the knee. The aim of this retrospective
      study was to find out clinical and radiological outcomes and related
      complications using the Oxford phase 3 prosthesis at a small-volume center.
      MATERIAL AND METHODS: In all, 95 Oxford unicompartmental knee arthroplasties (87
      patients) were performed between 2000 and 2010 in North Karelia Central Hospital.
      Of these, five patients had undergone revision surgery. In all, 52
      unicompartmental knee arthroplasties (46 patients) participated in this study.
      The mean age of patients was 61.4 years, and 78.2% of patients were females. Pain
      and function levels were evaluated by using the Knee Society score. Radiographic
      analyses were performed on preoperative and postoperative and follow-up
      radiographs. RESULTS AND CONCLUSIONS: The mean follow-up time was 6.5 years, and
      the Kaplan-Meier estimated 9-year implant survival rate was 88.9% (95% confidence
      interval = 78.7%-99.1%). The median Knee Society score of 77 (range: 18-93) at
      follow-up was considered good (range: 70-79). In this study, we found out that
      medial knee pain remains in 10% of unicompartmental knee arthroplasties several
      years after surgery, although the reason for the pain remained unclear. These mid
      term results are promising, and good results can be achieved also at a small
      volume center when strict patient selection is followed.

PMID- 25869307
TI  - Early IFN type I response: Learning from microbial evasion strategies.
AB  - Type I interferon (IFN) comprises a class of cytokines first discovered more than
      50 years ago and initially characterized for their ability to interfere with
      viral replication and restrict locally viral propagation. As such, their
      induction downstream of germ-line encoded pattern recognition receptors (PRRs)
      upon recognition of pathogen-associated molecular patterns (PAMPs) is a hallmark
      of the host antiviral response. The acknowledgment that several PAMPs, not just
      of viral origin, may induce IFN, pinpoints at these molecules as a first line of
      host defense against a number of invading pathogens. Acting in both autocrine and
      paracrine manner, IFN interferes with viral replication by inducing hundreds of
      different IFN-stimulated genes with both direct anti-pathogenic as well as
      immunomodulatory activities, therefore functioning as a bridge between innate and
      adaptive immunity. On the other hand an inverse interference to escape the IFN
      system is largely exploited by pathogens through a number of tactics and tricks
      aimed at evading, inhibiting or manipulating the IFN pathway, that result in
      progression of infection or establishment of chronic disease. In this review we
      discuss the interplay between the IFN system and some selected clinically
      important and challenging viruses and bacteria, highlighting the wide array of
      pathogen-triggered molecular mechanisms involved in evasion strategies. 

PMID- 25869308
TI  - Effects of solvent on the solution properties, structural characteristics and
      properties of silk sericin.
AB  - Sericin films have attracted much attention from researchers in biomedical and
      cosmetic fields because of its unique properties, including good
      cytocompatibility and its promotion of wound healing. However, poor mechanical
      properties of sericin films have restricted its application in these fields. In
      this study, a new solvent, formic acid, was used to fabricate sericin solutions
      and films. The effects of formic acid on the structural characteristics and
      mechanical properties of the sericin solutions and films were examined and
      compared with water. The sericin/formic acid solution showed fewer aggregated
      sericin molecules, resulting in a lower turbidity than that of the sericin/water
      solution. In addition, the gelation of the sericin solution was retarded in
      formic acid compared to that of water. Sericin films cast from the formic acid
      solution exhibited a much higher crystallinity index than that produced from
      water. The tensile strength and elongation of the sericin films cast from the
      formic acid solution were more than double that of the sericin films cast from
      water. It is expected that the more stable sericin solution and high
      crystallinity sericin films, which have significantly improved mechanical
      properties, produced by using formic acid as the solvent could be utilized in
      biomedical and cosmetic applications. 

PMID- 25869309
TI  - Isocitrate lyase of Mycobacterium tuberculosis is inhibited by quercetin through
      binding at N-terminus.
AB  - Combating tuberculosis requires new therapeutic strategies that not only target
      the actively dividing bacilli but also the dormant bacilli during persistent
      infection. Isocitrate lyase (ICL) is a key enzyme of the glyoxylate shunt,
      crucial for the survival of bacteria in macrophages and mice. MtbICL is
      considered as one of the potential and attractive drug targets against persistent
      infection. We report the inhibition of MtbICL by quercetin with IC50 of 3.57 MUM.
      In addition, quercetin strongly inhibited the growth of Mtb H37Rv utilizing
      acetate, rather than glucose as the sole carbon source, suggesting the inhibition
      of glyoxylate shunt. Quercetin binds at the N-terminus of MtbICL (Kd - 6.68 MUM).

PMID- 25869310
TI  - Hepatoprotective effect of a polysaccharide from Crassostrea gigas on acute and
      chronic models of liver injury.
AB  - A water-soluble polysaccharide was isolated from Crassostrea gigas (CGPS-1) by
      hot-water extraction, isoelectric precipitation, hydrolysis and ultrafiltration
      without using ethanol. Based on the calibration with Dextran, CGPS-1 had a
      molecular weight of approximately 6.5*10(6) Da. CGPS-1 was analyzed using high
      performance liquid chromatography, Fourier-transform infrared spectroscopy and
      (1)H and (13)C nuclear magnetic resonance spectroscopy. Based on the data, CGPS-1
      was found to be a uniform glucose polymer. The protective effect of CGPS-1 on
      acute carbon tetrachloride- and chronic ethanol-induced liver injury was
      investigated in mice. Treatment with CGPS-1 decreased serum aspartate
      aminotransferase (AST), serum alanine aminotransferase (ALT), and malondialdehyde
      (MDA) levels; increased superoxide dismutase (SOD) activity; and improved hepatic
      injury in both the acute and chronic models of liver injury in mice. These
      results suggest that CGPS-1 possesses potent hepatoprotective activity.

PMID- 25869311
TI  - Purification and characterization of a novel glycoprotein from Streptomyces sp.
      ZX01.
AB  - A novel glycoprotein GP-1 with antiviral activity against plant virus was
      isolated from the fermentation broth of the actinomycete Streptomyces sp. ZX01.
      MALDI-TOF-MS proved that molecular weight of GP-1 approximately was 8.5 kDa. GP-1
      was a heat-sensitive glycoprotein with decreasing antiviral activity after
      treated from 80  degrees C to 100  degrees C for 30 min. GP-1 contained 40.23%
      carbohydrate with N-linked and O-linked glycan. FT-IR and NMR spectra proved that
      GP-1 contained protein and carbohydrate portions with alpha-D-(1,6)-glucose
      residues. Circular dichroism revealed that GP-1 was a glycoprotein with a large
      unordered content. Moreover, protein sequencing was predicted by using MALDI-TOF
      MS and Mascot search. These results suggested that glycoprotein GP-1 could be
      used as a novel natural antiviral agent in agricultural industry.

PMID- 25869312
TI  - Comparison of physicochemical properties of B-type nontraditional starches from
      different sources.
AB  - Starches were isolated from rhizomes of Curcuma longa, Canna edulis and Canna
      indica and bulbs of Lilium lancifolium, and showed a B-type X-ray diffraction
      pattern. Their physicochemical properties were investigated and compared. These
      starches showed significantly different granule morphologies and sizes, but all
      had eccentric hila. The C. longa starch had the lowest content of amylopectin
      short branch-chain and branching degree and the highest content of amylopectin
      long branch-chain, and the L. lancifolium starch the highest content of
      amylopectin short branch-chain and branching degree and the lowest content of
      amylopectin long branch-chain among the four starches. The L. lancifolium starch
      had the lowest resistance to gelatinization, and showed the lowest pasting peak,
      hot and final viscosities, and the C. longa starch had the highest resistance to
      gelatinization, and showed the highest pasting hot, final and setback viscosities
      and the lowest pasting breakdown viscosity. The C. longa and L. lancifolium
      starches possessed very high and low resistance to hydrolysis and digestion,
      respectively. The above physicochemical properties would be useful for the
      applications of B-type starches in food and nonfood industries. 

PMID- 25869313
TI  - Electrocapillary coupling at rough surfaces.
AB  - We investigate the impact of the surface roughness on the experimental value of
      the electrocapillary coupling coefficient, sigma. This quantity relates the
      response of electrode potential, E, to tangential elastic strain, e, and also
      measures the variation of the surface stress, f, with the superficial charge
      density, q. We combine experiments measuring the apparent coupling coefficient
      sigmaeff for gold thin film electrodes in weakly adsorbing electrolyte with data
      for the surface roughness determined by atomic force microscopy and by the
      capacitance ratio method. We find that even moderate roughness has a strong
      impact on the value of sigmaeff. Analyzing the mechanics of corrugated surfaces
      affords a correction scheme yielding values of sigma that are invariant with
      roughness and that agree with expectations for the true coupling coefficient on
      ideal, planar surfaces. The correction is simple and readily applied to
      experiments measuring sigmaeff from surface stress changes in cantilever bending
      studies or from the potential variation in dynamic electro-chemo-mechanical
      analysis. 

PMID- 25869314
TI  - Evolution, recent progress and future development of optical coherence
      tomography.

PMID- 25869315
TI  - Click inspired synthesis of antileishmanial triazolyl O-benzylquercetin
      glycoconjugates.
AB  - The 1,3-dipolar cycloaddition of deoxy-azido sugars 1 with O-benzylquercetin
      alkynes (5-7) to afford regioselective triazole-linked O-benzylquercetin
      glycoconjugates (8-10) was investigated in the presence of CuI/DIPEA in
      dichloromethane. All the developed glycoconjugates (8-10) were evaluated for anti
      leishmanial activity against the promastigotes and amastigotes of Leishmania
      donovani. Graphical Abstract Click Inspired Synthesis of Antileishmanial
      Triazolyl O-Benzylquercetin Glycoconjugates. 

PMID- 25869316
TI  - Binding mode analysis of anti-influenza drugs in H1N1 (2009) and H5N1 influenza A
      virus and designing of potential H1N1 inhibitors.
AB  - The main goal of this study is to understand the molecular-level interactions of
      neuraminidase inhibitor. The molecular docking, molecular dynamics and binding
      energy calculation analyses were carried out and the results revealed that the
      150-cavitiy in the active site may play an important role in binding of drugs.
      Free energy calculations revealed that electrostatic interaction is more
      favourable for Oseltamivir interaction with H1N1 and van der Waals interaction is
      more favourable for H5N1, whereas Zanamivir favours the electrostatic interaction
      in both the strains (H1N1 and H5N1). Energy-optimised pharmacophore mapping was
      created using Oseltamivir drug. The pharmacophore model contained two hydrogen
      bond acceptor and two hydrogen bond donor sites. Using these pharmacophore
      features, we screened a compound database to find a potential ligand that could
      inhibit the H1N1 protein. The current research will pave the way to find potent
      neuraminidase inhibitors against H1N1 (2009) strain. 

PMID- 25869317
TI  - Natural flavonoid derivatives as oral human epidermoid carcinoma cell inhibitors.
AB  - Natural flavonoid derivatives against cancer for selective KB cell lines (oral
      human epidermoid carcinoma) are analysed to determine the relationship between
      biological activities and structural properties of these molecules. Molecular
      alignment was performed for 88 natural flavonoid derivatives; out of these 88
      molecules, 69 molecules were taken into training set and rest of the 19 molecules
      were used in test set prediction. We describe our elucidation of their structure
      activity relation (SAR) using three-dimensional quantitative structure activity
      relationship (3D-QSAR) models. A predictive comparative molecular field analysis
      (CoMFA) model of q2 = 0.888 and r2 = 0.940 was obtained and a comparative
      molecular similarity indices analysis (CoMSIA) model q2 = 0.778 and r2 = 0.971
      was used to describe the non-linearly combined affinity of each functional group
      in the inhibitors. The contour maps obtained from 3D-QSAR studies were evaluated
      for the activity trends of the molecules analysed. 

PMID- 25869318
TI  - In silico prediction of anti-malarial hit molecules based on machine learning
      methods.
AB  - Machine learning techniques have been widely used in drug discovery and
      development in the areas of cheminformatics. Aspartyl aminopeptidase (M18AAP) of
      Plasmodium falciparum is crucial for survival of malaria parasite. We have
      created predictive models using weka and evaluated their performance based on
      various statistical parameters. Random Forest based model was found to be the
      most specificity (97.94%), with best accuracy (97.3%), MCC (0.306) as well as ROC
      (86.1%). The accuracy and MCC of these models indicated that they could be used
      to classify huge dataset of unknown compounds to predict their antimalarial
      compounds to develop effective drugs. Further, we deployed best predictive model
      on NCI diversity set IV. As result we found 59 bioactive anti-malarial molecules
      inhibiting M18AAP. Further, we obtained 18 non-toxic hit molecules out of 59
      bioactive compounds. We suggest that such machine learning approaches could be
      applied to reduce the cost and length of time of drug discovery. 

PMID- 25869319
TI  - A novel formulation of veggies with potent anti-migraine activity.
AB  - Calcitonin gene-related peptide (CGRP) is involved in triggering migraine. Many
      strategies for antimigraine drug designing have been employed using various CGRP
      antagonist/ligands but most of them have failed due to their inability to reach
      target CGRP receptor as they get metabolised before conferring their
      pharmacological action and they are also toxic to the liver. In the present
      study, we evaluated the binding of our active ligands present in real veggies
      with the CGRP receptor crystal structure and compared their binding energy and
      affinity with other reference anti-migraine drugs/ligands present in the market.
      A high-throughput screening comprising of molecular docking, Absorption,
      Distribution, Metabolism, Excretion and Toxicity predictions, logP values and %
      of human oral absorption value led to the identification of two potential
      compounds present in live green real veggies which could be considered for anti
      migraine activity with better binding affinities than the reference drugs used
      and with liver-protective properties. 

PMID- 25869320
TI  - In silico phylogenetic analysis of Vibrio cholerae isolates based on three
      housekeeping genes.
AB  - Vibrio cholera, a gram-negative bacterium, has been categorised into clinical and
      environmental species. Phylogenetic studies have been performed to investigate
      the relationships of the V. cholerae populations in worldwide. In this study,
      phylogenetic relationship between V. cholerae isolates from Iran and other
      regions of the world was determined, based on three housekeeping genes analysis.
      Results for Iranian strains showed that congruency of asd and hlyA phylogenetic
      trees were remarkably higher than recA tree. Iranian strains displayed 2-3%, 1
      14% and 3-5% deference in asd, hlyA and recA nucleotide sequences, respectively.
      Sequence similarity degrees were variable between Iranian and other region's
      strains. Furthermore, the non-congruence in the phylogeny of the pathogenic
      clones in cladograms is probably due to horizontal gene transfer. Finally,
      results of this study suggest that monitoring of surface waters for housekeeping
      genes of V. cholerae in the cholera endemic areas may be valuable for forecasting
      the expected cholera outbreaks. 

PMID- 25869321
TI  - A novel formulation of veggies with potent liver detoxifying activity.
AB  - LXR (encoded by NR1H2 and 3) and FXR (known as bile acid receptor) encoded by
      NR1H4 (nuclear receptor subfamily 1, group H and member 4) are nuclear receptors
      in humans and are important regulators of bile acid production, cholesterol,
      fatty acid and glucose homeostasis hence responsible for liver detoxification.
      Several strategies for drug design with numerous ligands for this target have
      failed owing to the inability of the ligand to access the target/receptor or
      their early metabolisation. In this work, we have evaluated FXR and LXR structure
      bound with agonist and compared the binding energy affinity of active ligands
      present in live green-real veggies with reference drugs (ligands) present in the
      market. A high throughput screening combined with molecular docking, absorption,
      distribution, metabolism, excretion and toxicity (ADMET) predictions, log P
      values and percentage of human oral absorption value led to the identification of
      two compounds present in live green-real veggies with strong potential for liver
      detoxification. 

PMID- 25869322
TI  - Development of a novel carrier optimized for cell sheet transplantation.
AB  - Tissue engineering is a rapidly advancing technology in the field of regenerative
      medicine. For the transplantation of cell sheets, a carrier must maintain the
      shape of a cell sheet from a culture dish to affected sites as well as release
      the sheet easily onto the lesion. In this study, we examined the utility of a
      novel, poly(lactic acid)-based carrier for cell sheets transplantation to the
      cornea of dogs and the skin of rats. The poly(lactic acid)-based carrier easily
      picked a cell sheet up from the dish, fit to the shape of the transplantation
      sites, and saved time for cell sheets detachment comparing to a conventional
      carrier. Thus, the poly(lactic acid)-based carrier would be useful for easy cell
      sheet transplantations. 

PMID- 25869323
TI  - Identification and characterization of calcium transporter gene family in finger
      millet in relation to grain calcium content.
AB  - Calcium (Ca) is an essential mineral for proper growth and development of plants
      as well as animals. In plants including cereals, calcium is deposited in seed
      during its development which is mediated by specialized Ca transporters. Common
      cereal seeds contain very low amounts of Ca while the finger millet (Eleusine
      coracana) contains exceptionally high amounts of Ca in seed. In order to
      understand the role of Ca transporters in grain Ca accumulation, developing seed
      transcriptome of two finger millet genotypes (GP-1, low Ca and GP-45 high Ca)
      differing in seed Ca content was sequenced using Illumina paired-end sequencing
      technology and members of Ca transporter gene family were identified. Out of
      109,218 and 120,130 contigs, 86 and 81 contigs encoding Ca transporters were
      identified in GP-1 and GP-45, respectively. After removal of redundant sequences,
      a total of 19 sequences were confirmed as Ca transporter genes, which includes 11
      Ca(2+) ATPases, 07 Ca(2+)/cation exchangers and 01 Ca(2+) channel. The
      differential expressions of all genes were analyzed from transcriptome data and
      it was observed that 9 and 3 genes were highly expressed in GP-45 and GP-1
      genotypes respectively. Validation of transcriptome expression data of selected
      Ca transporter genes was performed on different stages of developing spikes of
      both genotypes grown under different concentrations of exogenous Ca. In both
      genotypes, significant correlation was observed between the expression of these
      genes, especially EcCaX3, and on the amount of Ca accumulated in seed. The
      positive correlation of seed mass with the amount of Ca concentration was also
      observed. The efficient Ca transport property and responsiveness of EcCAX3
      towards exogenous Ca could be utilized in future biofortification program. 

PMID- 25869324
TI  - Use of ibuprofen to assess inflammatory biomarkers in induced sputum:
      Implications for clinical trials in cystic fibrosis.
AB  - BACKGROUND: High-dose ibuprofen (HDI) is a clinically beneficial anti
      inflammatory regimen that may be a useful reagent to study induced sputum
      inflammatory marker changes over short study periods appropriate for early-phase
      CF clinical trials. METHODS: We conducted a 28-day, open-label, randomized,
      controlled trial among 72 clinically stable CF subjects (FEV1>=40% predicted)
      randomized to HDI or routine care that assessed IL-6, IL-8, TNF-alpha, IL-1-beta,
      free neutrophil elastase, and white cell counts with differentials change from
      baseline in induced sputum. RESULTS: IL-6 was the only biomarker with significant
      within-group change: 0.13 log10 pg/mL mean reduction among ibuprofen-treated
      subjects (p=0.04); and no change in the control group. IL-6 change between groups
      was statistically significant (p=0.024). No other inflammatory biomarker
      differences were observed between groups after 28 days. CONCLUSION: Although we
      studied only one agent, HDI, these results suggest that one month may be
      inadequate to assess anti-inflammatory candidates using markers from induced
      sputum.

PMID- 25869325
TI  - Cystic fibrosis transmembrane conductance regulator gene variants are associated
      with autoimmune pancreatitis and slow response to steroid treatment.
AB  - BACKGROUND: Autoimmune pancreatitis (AIP) is a distinct type of chronic
      pancreatitis. To date, the association of CFTR gene variants with AIP has not
      been studied. METHODS: The entire coding and intronic regions of the CFTR gene
      were examined using next-generation sequencing in 89 AIP patients. Clinical
      features, including imaging, histology, serology, steroid treatment response and
      extra-pancreatic involvement, were compared between AIP patients with and without
      CFTR gene variants. RESULTS: A total of 28.1% (25/89) of the AIP patients carried
      26 CFTR variants, including nine with I556V, seven with 5T, four with S42F, two
      with I125T, and one each with R31C, R553X, S895N, and G1069R. The presence of
      CFTR variants and age was independent predictors of the response to steroid
      treatment, as shown by multivariate analysis. CONCLUSIONS: CFTR variants are
      associated with AIP. Because AIP patients with CFTR variants show slower and
      reduced steroid treatment responses, different treatments should be considered in
      AIP patients with CFTR variants.

PMID- 25869326
TI  - HbA1c as a screening tool for cystic fibrosis related diabetes.
AB  - AIMS: Early diagnosis of cystic fibrosis (CF) related diabetes (CFRD) is
      important to improve outcomes. International guidelines recommend an oral glucose
      tolerance test (OGTT) for all CF patients aged >=10 years - this approach is
      controversial. The aim of this study was to develop an effective screening tool
      and reduce the need for a universal OGTT. METHODS: Adult CF patients (without
      CFRD) attending an annual review assessment were recruited prospectively (March
      2009-July 2012) into two sequential studies - a primary investigative study
      followed by validation study. All patients underwent an OGTT and were
      simultaneously screened by predetermined biochemical/clinical criteria to
      identify their risk of CFRD. A sensitivity/specificity analysis was performed
      using the World Health Organisation diabetes criteria as gold standard;
      modifications were made to improve the screening tool's accuracy and determine
      the optimal screening thresholds. This was tested in the validation study.
      RESULTS: 429 patients (primary, n=94; validation, n=335: mean age=31.7 +/-
      10.4(SD), 43% female, 77% on pancreatic supplements). Primary study: in
      predicting a positive OGTT, the test sensitivity was 66.7% and specificity 60%.
      HbA1c was carried over to the validation study as it was the most discriminative
      (optimal threshold >=5.8% (40 mmol/mol); receiver operating curve, ROC, score
      0.60). Validation study: the number of patients with a normal, impaired and
      diabetic OGTT was 268(80%), 51(15.2%) and 16(4.8%), respectively. HbA1c provided
      a test sensitivity, specificity and ROC score of 93.8%, 53.0% and 0.73,
      respectively. CONCLUSIONS: The use of HbA1c >= 5.8%(40 mmol/mol) is an effective
      tool for CFRD screening and reduced the need for an OGTT by 50.7%.

PMID- 25869327
TI  - Peer Victimization and DRD4 Genotype Influence Problem Behaviors in Young
      Children.
AB  - Decades of research supports the presence of significant genetic influences on
      children's internalizing (emotional), externalizing (acting out), and social
      difficulties, including victimization. Additionally, being victimized has been
      shown to relate to further behavioral problems. The current study assessed the
      nature of the gene-environment relationships between the DRD4 gene, peer
      victimization, and externalizing and internalizing difficulties in 6- to 10-year
      old children. 174 children (56 % girls; 88.6 % Caucasian, 3.4 % African American,
      8 % mixed race or Mayan) and their parents were administered victimization and
      problem behavior questionnaires, and DRD4 was genotyped for the children. An
      interaction between genes (DRD4) and environment (victimization) was significant
      and supported the differential susceptibility model for verbal victimization and
      child-reported externalizing behaviors. Children with the DRD4 7-repeat allele
      were differentially responsive to the verbal victimization environment, such that
      those experiencing little to no victimization reported significantly lower levels
      of externalizing behaviors, but if they experienced high amounts of
      victimization, they reported the highest levels of externalizing behaviors. Thus,
      consideration of how genes and environment affect children's experiences of
      victimization prior to adolescence is essential for understanding the trajectory
      of both externalizing and internalizing behaviors during adolescent development. 

PMID- 25869328
TI  - Acetylcholinesterase is associated with a decrease in cell proliferation of
      hepatocellular carcinoma cells.
AB  - Acetylcholinesterase (AChE), the enzyme that rapidly splits acetylcholine into
      acetate and choline, presents non-cholinergic functions through which may
      participate in the control of cell proliferation and apoptosis. These two
      features are relevant in cancer, particularly in hepatocellular carcinoma (HCC),
      a very aggressive liver tumor with high incidence and poor prognosis in advanced
      stages. Here we explored the relation between acetylcholinesterase and HCC growth
      by testing the influence of AChE on proliferation of Huh-7 and HepG2 cell lines,
      addressed in monolayer cultures, spheroid formation and human liver tumor
      samples. Results showed a clear relation in AChE expression and cell cycle
      progression, an effect which depended on cell confluence. Inhibition of AChE
      activity led to an increase in cell proliferation, which was associated with
      downregulation of p27 and cyclins. The fact that Huh-7 and HepG2 cell lines
      provided similar results lent weight to the relationship of AChE expression with
      cell cycle progression in hepatoma cell lines at least. Human liver tumor samples
      exhibited a decrease in AChE activity as compared with normal tissue. The
      evidence presented herein provides additional support for the proposed tumor
      suppressor role of AChE, which makes it a potential therapeutic target in
      therapies against hepatocellular carcinoma. 

PMID- 25869330
TI  - Knowledge and awareness of personal sickle cell genotype among parents of
      children with sickle cell disease in southeast Nigeria.
AB  - Sickle cell trait (SCT; HbAS), the heterozygous state for the sickle cell allele
      of the beta globin gene, is carried by as many as 100 million individuals
      worldwide. Nigeria has the highest prevalence of SCT, impacting an estimated 25 %
      of adult population. This study was designed to assess timing of awareness,
      knowledge of SCT status and preferred method of education among parents of
      children with sickle cell disease (SCD). We conducted a cross-sectional survey of
      parents of children with SCD from June 2013-March 2014. Participants completed a
      20-item questionnaire to assess (1) awareness of personal sickle cell genotype,
      (2) timing of awareness of personal sickle cell genotype, and (3) knowledge of
      SCT. One hundred and fifty-five participants completed the survey. Seventy-eight
      percent were females, and 87 % (135/155) were aware of their own sickle cell
      genotype. Timing of awareness varied as follows: following birth of a child with
      sickle cell disease (45 %); during marriage (21.5 %); school admission (9.6 %);
      during pregnancy (9.6 %); and other times (14 %). Approximately 35.5 % of
      participants thought that sickle cell trait was a mild form of sickle cell
      disease. Radio (43.9 %), informational community meetings (27.7 %), and
      television (21.9 %) were identified by participants as the most effective method
      of increasing sickle cell trait awareness. Innovative approaches are needed to
      increase the proportion of individuals who are aware of their own sickle cell
      genotype prior to having a child with sickle cell anemia in line with the Healthy
      People 2020 objective. 

PMID- 25869329
TI  - Chromosome 21-derived hsa-miR-155-5p regulates mitochondrial biogenesis by
      targeting Mitochondrial Transcription Factor A (TFAM).
AB  - The regulation of mitochondrial biogenesis is under the control of nuclear genes
      including the master Mitochondrial Transcription Factor A (TFAM). Recent evidence
      suggests that the expression of TFAM is regulated by microRNAs (miRNAs) in
      various cellular contexts. Here, we show that hsa-miR-155-5p, a prominent miRNA
      encoded in chromosome 21, controls the expression of TFAM at the post
      transcriptional level. In human fibroblasts derived from a diploid donor,
      downregulation of TFAM by hsa-miR-155-5p decreased mitochondrial DNA (mtDNA)
      content. In contrast, downregulation of TFAM by hsa-miR-155-5p did not decrease
      mtDNA content in fibroblasts derived from a donor with Down syndrome (DS, trisomy
      21). In line, downregulation of mitochondrial TFAM levels through hsa-miR-155-5p
      decreased mitochondrial mass in diploid fibroblasts but not in trisomic cells.
      Due to the prevalence of mitochondrial dysfunction and cardiac abnormalities in
      subjects with DS, we examined the presence of potential associations between hsa
      miR-155-5p and TFAM expression in heart samples from donors with and without DS.
      There were significant negative associations between hsa-miR-155-5p and TFAM
      expression in heart samples from donors with and without DS. These results
      suggest that regulation of TFAM by hsa-miR-155-5p impacts mitochondrial
      biogenesis in the diploid setting but not in the DS setting. 

PMID- 25869331
TI  - Inorganic polyphosphates are important for cell survival and motility of human
      skin keratinocytes.

PMID- 25869332
TI  - Advances in toponomics drug discovery: Imaging cycler microscopy correctly
      predicts a therapy method of amyotrophic lateral sclerosis.
AB  - An imaging cycler microscope (ICM) is a fully automated (epi)fluorescence
      microscope which overcomes the spectral resolution limit resulting in parameter-
      and dimension-unlimited fluorescence imaging. This enables the spatial resolution
      of large molecular systems with their emergent topological properties (toponome)
      in morphologically intact cells and tissues displaying thousands of multi protein
      assemblies at a time. The resulting combinatorial geometry of these systems has
      been shown to be key for in-vivo/in-situ detection of lead proteins controlling
      protein network topology and (dys)function: If lead proteins are blocked or
      downregulated the corresponding disease protein network disassembles. Here,
      correct therapeutic predictions are exemplified for ALS. ICM drug target studies
      have discovered an 18-dimensional cell surface molecular system in ALS-PBMC with
      a lead drug target protein, whose therapeutic downregulation is now reported to
      show statistically significant effect with stop of disease progression in one
      third of the ALS patients. Together, this clinical and the earlier experimental
      validations of the ICM approach indicate that ICM readily discovers in vivo
      robustness nodes of disease with lead proteins controlling them. Breaking in vivo
      robustness nodes using drugs against their lead proteins is likely to overcome
      current high drug attrition rates.

PMID- 25869333
TI  - Infection levels of the cestode Hymenolepis diminuta in rat populations from
      Buenos Aires, Argentina.
AB  - Ecological studies on zoonotic parasites are crucial for the design and
      implementation of effective measures to prevent parasite transmission. The aim of
      this study was to evaluate factors such as season, landscape unit, rat sex and
      rat body length, affecting the abundance of the cestode Hymenolepis diminuta, a
      parasite of synanthropic rats, within an urban environment. A parasitological
      survey was undertaken on 169 rats from landscape units such as shantytowns,
      parklands, industrial-residential areas and scrap-metal yards in Buenos Aires,
      Argentina. The overall prevalence of H. diminuta was 21.3%, although the
      occurrence of this species in rats was not homogeneous. The abundance of H.
      diminuta, using a zero-inflated negative binomial model, was correlated with rat
      body length. In shantytowns, abundance levels were higher than other landscape
      units, largely due to differences in individual environmental characteristics and
      rat assemblages. The populations of arthropod intermediate hosts could be
      subjected to seasonal fluctuations and the degree of urbanization. Shantytowns
      are overcrowded urban marginal settlements with most inhabitants living in
      precarious conditions and supporting large populations of rats, thereby
      increasing the risk of zoonotic infection. 

PMID- 25869334
TI  - Palliative care: Discontinuation of statins assessed.

PMID- 25869335
TI  - Risk factors: Carotid plaque in adulthood after childhood exposure to parental
      smoking.

PMID- 25869336
TI  - Assessing serum hemoglobin levels without venipuncture: accuracy and reliability
      of Pronto-7 noninvasive spot-check device.
AB  - BACKGROUND: Hemoglobin is a frequently obtained test in hospital settings. We
      analyzed accuracy of a noninvasive device compared to standard laboratory
      analyzers in a variety of settings. METHODS: A noninvasive hemoglobin monitoring
      device was analyzed for reliability, correlation, precision, and bias. Hemoglobin
      levels were obtained from standard laboratory and point-of-care hemoglobin
      analyzers and compared to noninvasive hemoglobin in inpatient and military field
      environments. RESULTS: Ninety-seven patients were enrolled. Overall, the
      noninvasive hemoglobin device had high correlation compared to invasive
      laboratory values. Stratified by location, the device had high correlation in
      hospital and low correlation in austere environment. The highest variation in
      accuracy was seen in the austere environment. CONCLUSIONS: Overall, the
      noninvasive spot-check hemoglobin device is reliable and highly correlates to
      standard hemoglobin analysis. Use in an austere setting requires further study.

PMID- 25869338
TI  - PET/CT imaging for target volume delineation in curative intent radiotherapy of
      non-small cell lung cancer: IAEA consensus report 2014.
AB  - This document describes best practice and evidence based recommendations for the
      use of FDG-PET/CT for the purposes of radiotherapy target volume delineation
      (TVD) for curative intent treatment of non-small cell lung cancer (NSCLC). These
      recommendations have been written by an expert advisory group, convened by the
      International Atomic Energy Agency (IAEA) to facilitate a Coordinated Research
      Project (CRP) aiming to improve the applications of PET based radiation treatment
      planning (RTP) in low and middle income countries. These guidelines can be
      applied in routine clinical practice of radiotherapy TVD, for NSCLC patients
      treated with concurrent chemoradiation or radiotherapy alone, where FDG is used,
      and where a calibrated PET camera system equipped for RTP patient positioning is
      available. Recommendations are provided for PET and CT image visualization and
      interpretation, and for tumor delineation using planning CT with and without
      breathing motion compensation. 

PMID- 25869337
TI  - Agreement in the assessment of metastatic spine disease using scoring systems.
AB  - PURPOSE: To assess variability in the use of Tomita and modified Bauer scores in
      spine metastases. MATERIALS AND METHODS: Clinical data and imaging from 90
      patients with biopsy-proven spinal metastases, were provided to 83 specialists
      from 44 hospitals. Spinal levels involved and the Tomita and modified Bauer
      scores for each case were determined twice by each clinician, with a minimum of 6
      week interval. Clinicians were blinded to every evaluation. Kappa statistic was
      used to assess intra and inter-observer agreement. Subgroup analyses were
      performed according to clinicians' specialty (medical oncology, neurosurgery,
      radiology, orthopedic surgery and radiation oncology), years of experience (?7, 8
      13, ?14), and type of hospital (four levels). RESULTS: For metastases
      identification, intra-observer agreement was "substantial" (0.60<k<0.80) at
      sacrum, and "almost perfect" (k>0.80) at the other levels. Inter-observer
      agreement was "almost perfect" at lumbar spine, and "substantial" at the other
      levels. Intra-observer agreement for the Tomita and Bauer scores was almost
      perfect. Inter-observer agreement was almost perfect for the Tomita score and
      substantial for the Bauer one. Results were similar across specialties, years of
      experience and type of hospital. CONCLUSION: Agreement in the assessment of
      metastatic spine disease is high. These scoring systems can improve communication
      among clinicians involved in oncology care.

PMID- 25869339
TI  - Employment after lung transplantation--a single-center cross-sectional study.
AB  - BACKGROUND: 359 lung transplantations were performed in Germany in 2013. The main
      goals of lung transplantation are to prolong survival and improve the quality of
      life. Both of these goals can be reflected in a return to employment. We report
      the first study of employment after lung transplantation in Germany. METHODS: We
      evaluated the findings of a single-center, questionnaire-based cross-sectional
      investigation of the social and economic situation of 531 patients (September
      2009 to March 2010) and obtained 5-year follow-up data in December 2014. RESULTS:
      38% of the patients were employed after lung transplantation. They took a mean of
      ten sick days off from work each year; they did not have infections or organ
      rejection any more frequently than other patients. The fiveyear follow-up data
      showed no difference in the overall survival rate of employed and unemployed
      patients. Employment was associated with a better quality of life (80%
      [interquartiles: 70%, 95%]) versus 75% [interquartiles: 50%, 85%], p = 0.001).
      Factors associated with a return to employment included a higher educational
      level (odds ratio [OR] 2.6, 95%confidence interval [CI] 1.7-4, p = 0.001) and
      better physical fitness (OR 2, 95%CI 1.3-3.2, p = 0.001). CONCLUSION: The rate of
      return to work after lung transplantation in Germany is similar to the rates
      observed in other countries. The findings of this study imply that employment
      improves the quality of life and does not endanger health. Thus, patients who
      have received lung transplants should be advised to return to work if possible.

PMID- 25869340
TI  - Current data.

PMID- 25869341
TI  - In reply.

PMID- 25869342
TI  - Case report.

PMID- 25869343
TI  - In reply.

PMID- 25869344
TI  - Fumaric acid esters as an additional systemic therapy option.

PMID- 25869345
TI  - Acatalasia was omitted.

PMID- 25869346
TI  - In reply.

PMID- 25869347
TI  - The epidemiology, diagnosis, and treatment of Barrett's carcinoma.
AB  - BACKGROUND: Roughly 3000 new cases of Barrett's carcinoma arise in Germany each
      year. In view of recent advances in the epidemiology, diagnosis, and treatment of
      this disease, an update of the clinical recommendations is in order. METHODS:
      This review is based on selected relevant publications, including current
      reviews, meta-analyses, and guidelines. RESULTS: The risk of progression of
      Barrett's esophagus to carcinoma lies between 0.10% and 0.15% per year. Risk
      factors for progression include male sex, age over 50 years, obesity,
      longstanding and frequent reflux symptoms, smoking, length of the Barrett's
      esophagus, and intraepithelial neoplasia. Well-differentiated carcinomas that are
      confined to the esophageal mucosa can be resected endoscopically with a cure rate
      above 90%. For more advanced, but still locally confined tumors, surgical
      resection is the treatment of choice. In stages cT3/4, the prognosis can be
      improved with neo-adjuvant chemo - therapy or combined radiotherapy and
      chemotherapy. Metastatic Barrett's carcinoma can be treated by endoscopic,
      chemotherapeutic, radiotherapeutic, and palliative methods. CONCLUSION: Early
      carcinoma can often be cured by endoscopic resection. Locally advanced carcinoma
      calls for multimodal treatment. Current research focuses on means of preventing
      the progression of Barrett's esophagus, the scope of applicability of endoscopic
      techniques, and the optimization of multimodal treatment strategies for advanced
      disease.

PMID- 25869348
TI  - Promotion of health-enhancing physical activity in rheumatoid arthritis: a
      comparative study on healthcare providers in Italy, The Netherlands and Sweden.
AB  - The objectives of this study were to compare attitudes, practice of advice,
      perceived competencies and educational needs related to health-enhancing physical
      activity (HEPA) in rheumatoid arthritis (RA) among Dutch, Italian and Swedish
      healthcare providers (HCP) and to explore associations between these factors and
      age, gender and HEPA levels of HCP. Questionnaires were sent to 2939 HCP, members
      of their national rheumatology organizations. HEPA was assessed with the Short
      Questionnaire to Assess Health-Enhancing Physical Activity or the International
      Physical Activity Questionnaire; attitudes, practice of advice, perceived
      competencies and educational needs with a 23-item questionnaire. Overall response
      rate was 33 %. Ninety-five percent of HCP agreed that HEPA is an important health
      goal in RA. More Swedish HCP had positive attitudes to the attainability and
      safety of HEPA in RA. There were no differences between countries in practice of
      advice on HEPA to patients with RA in general or to those with recent onset
      disease, but more Italian HCP were reluctant to advise HEPA to patients with
      established disease. Of the total HCP, 36 to 60 % used public health guidelines
      to advise on HEPA, with Dutch HCP taking less advantage. Still they estimated a
      higher proportion of patients with RA to follow such advice. Italian HCP
      perceived their competencies the highest, but were also more interested in
      education to promote HEPA. Gender, age and HEPA performance had no association
      with attitudes toward HEPA, while a number of associations were found between
      these factors and practice of advice and perceived competencies. The differences
      found between HCP in the three countries might indicate the need for educational
      initiatives to improve HEPA promotion. 

PMID- 25869349
TI  - How is the experience of pain measured in older, community-dwelling people with
      osteoarthritis? A systematic review of the literature.
AB  - The objective of the study was to perform a systematic review to identify and
      appraise outcome measures and measures of pain that are used to assess the
      experience of pain by older people with osteoarthritis, and to assess whether
      these measures are effective at capturing the multidimensional nature of the
      experience of this pain. A systematic review of five electronic databases from
      January 1996 to March 2013 was done. Inclusion criteria were cohort/observational
      and cross-sectional studies; specific diagnosis of OA; employed outcome measures
      of pain and/or health and/or quality of life which included questions about pain;
      and considered older adults. Articles were reviewed for methodological quality
      using the Effective Public Health Practice Project Quality Assessment Tool for
      Quantitative Studies. A total of 14 publications met the inclusion criteria, and
      11 discrete studies were included in the review. The studies used 21 different
      outcome measures, utilizing 13 measures of pain. Sensory, affective and cognitive
      dimensions of pain were captured by the measures, albeit studies predominantly
      measured intensity or severity alone. Measures of pain used in epidemiological
      studies do not adequately capture the multidimensional nature of the experience
      of pain in osteoarthritis. There is a fraught complexity in the
      multidimensionality of the experience of pain in osteoarthritis, and studies
      exploring osteoarthritis pain in older people should attempt to capture this
      multidimensionality by employing multiple valid and reliable outcome measures
      that capture specific dimensions of the pain experience. 

PMID- 25869351
TI  - Singlet oxygen generation from Li+@C+60 nano-aggregates dispersed by laser
      irradiation in aqueous solution.
AB  - Laser pulse irradiation of a deaerated aqueous solution containing the solid
      state lithium ion-encapsulated fullerene resulted in the formation of highly
      dispersed nano-aggregates (Li(+)@C60)n. Photoirradiation of an O2-saturated D2O
      solution containing (Li(+)@C60)n gave singlet oxygen with 55% quantum yield,
      leading to efficient double-stranded DNA cleavage. 

PMID- 25869350
TI  - Diagnostic Performance of Coronary CT Angiography and Myocardial Perfusion
      Imaging in Kidney Transplantation Candidates.
AB  - OBJECTIVES: The goal of this study was to compare the diagnostic accuracy of the
      coronary artery calcium score (CACS), coronary computed tomography angiography
      (CTA), single-photon emission computed tomography (SPECT), and a combination of
      these tools in the diagnosis of obstructive coronary artery disease (CAD) in
      patients with chronic kidney disease referred for cardiac evaluation before
      kidney transplantation. BACKGROUND: The optimal method for the detection of
      obstructive CAD in potential kidney transplant patients has not yet been
      identified. Previous studies have found that established noninvasive stress tests
      have low diagnostic accuracy, while the diagnostic performance of coronary CTA
      remains unknown. METHODS: We prospectively studied 138 patients referred for pre
      transplant cardiac evaluation (mean age 54 years; age range 22 to 72 years; 68%
      male; 43% treated with dialysis). All patients underwent CACS, coronary CTA,
      SPECT, and invasive coronary angiography. The results of the noninvasive tests
      were merged into integrated hybrid imaging results: Hybrid (CACS/SPECT) and
      Hybrid (coronary CTA/SPECT). RESULTS: The overall prevalence of obstructive CAD
      (>=50% reduction in luminal diameter) according to quantitative invasive coronary
      angiography was 22%. Two-thirds of the patients with obstructive CAD had a
      stenosis located in a proximal coronary segment. In a patient-level model, the
      sensitivity and specificity, respectively, for diagnosing obstructive CAD were as
      follows: CACS (threshold of 400), 67% and 77%; coronary CTA, 93% and 63%; SPECT,
      53% and 82%; Hybrid (CACS/SPECT), 33% and 97%; and Hybrid (coronary CTA/SPECT),
      67% and 86%. The sensitivity for diagnosing obstructive CAD in a proximal segment
      was 70% for CACS (threshold 400), 100% for coronary CTA, 60% for SPECT, 40% for
      Hybrid (CACS/SPECT), and 75% for Hybrid (coronary CTA/SPECT). CONCLUSIONS:
      Coronary CTA is a reliable test with high sensitivity and a high negative
      predictive value for diagnosing obstructive CAD before kidney transplantation. A
      noninvasive approach with use of either coronary CTA or a combination of coronary
      CTA and SPECT to rule out obstructive CAD seems recommendable in kidney
      transplant candidates. (ACToR-Study: Angiographic CT of Renal Transplantation
      Candidate-Study; NCT01344434).

PMID- 25869352
TI  - Ablation of ventricular tachycardia in the very elderly patient with
      cardiomyopathy: how old is too old?
AB  - BACKGROUND: Because of the disputable effectiveness of the implantable
      cardioverter-defibrillator (ICD) in very elderly patients, it is reasonable to
      consider catheter ablation of scar-related ventricular tachycardia (VT) at an
      earlier stage of the therapeutic cascade, especially in those who have refused
      ICD implantation. METHODS: Analysis of 53 VT ablations performed in our tertiary
      centre in patients with ischemic or nonischemic dilated cardiomyopathy who were
      >= 60 years of age. We assessed the safety and acute effectiveness of the
      procedure in 14 very elderly patients (age >= 80 years), follow-up all-cause
      mortality and rates of ICD therapies during follow-up. Furthermore, we
      established a comparison between very elderly patients and: (1) 34 patients aged
      60-79 years having the same procedure; and (2) 11 octogenarian patients with
      ischemic or nonischemic cardiomyopathy, documented ventricular fibrillation or
      sustained VT, subsequent secondary prevention ICD implantation and at least 1 ICD
      therapy after implantation. RESULTS: Complete acute success was achieved in 80%
      of procedures in very elderly patients vs 91.7% in younger individuals. Three
      complications occurred in the former, including 1 periprocedural death not
      directly related to the procedure itself, and 2 were seen in the latter. A 6
      month 27.3% occurrence of any ICD therapy was seen in the very elderly group
      (with only 1 patient who required an ICD shock), and the 6-month incidence of ICD
      therapies in the younger group was 32%. All 11 control octogenarian ICD patients
      had further ICD therapies after their first ICD intervention. CONCLUSIONS:
      Ablation of VT in very elderly patients seems relatively safe and as effective as
      in younger patients.

PMID- 25869353
TI  - In Operando Monitoring of the Pore Dynamics in Ordered Mesoporous Electrode
      Materials by Small Angle X-ray Scattering.
AB  - To monitor dynamic volume changes of electrode materials during electrochemical
      lithium storage and removal process is of utmost importance for developing high
      performance lithium storage materials. We herein report an in operando probing of
      mesoscopic structural changes in ordered mesoporous electrode materials during
      cycling with synchrotron-based small angel X-ray scattering (SAXS) technique. In
      operando SAXS studies combined with electrochemical and other physical
      characterizations straightforwardly show how porous electrode materials underwent
      volume changes during the whole process of charge and discharge, with respect to
      their own reaction mechanism with lithium. This comprehensive information on the
      pore dynamics as well as volume changes of the electrode materials will not only
      be critical in further understanding of lithium ion storage reaction mechanism of
      materials, but also enable the innovative design of high performance
      nanostructured materials for next generation batteries. 

PMID- 25869354
TI  - Predicting and treating stress-induced vulnerability to epilepsy and depression.
AB  - Accumulation of stressful events can render individuals susceptible to develop
      epilepsy and comorbidities. Whether such vulnerability can be predicted and
      reversed is not known. Here we show that social defeat, although not producing
      depression by itself, produced in 50% of rats reduced threshold for status
      epilepticus (SE), accelerated epileptogenesis, and once epilepsy was induced,
      depression-like profile and cognitive deficits. Low serum brain-derived
      neurotrophic factor (BDNF) levels measured before SE identified this vulnerable
      population. Treatment with a BDNF analog before SE prevented the occurrence of
      comorbidities. Thus, vulnerability to comorbidities after epilepsy onset due to
      unresolved past stressful events may be predicted and reversed.

PMID- 25869355
TI  - Prospects for using self-assembled nucleic acid structures.
AB  - According to the central dogma in molecular biology, nucleic acids are assigned
      with key functions on storing and executing genetic information in any living
      cell. However, features of nucleic acids are not limited only with properties
      providing template-dependent biosynthetic processes. Studies of DNA and RNA
      unveiled unique features of these polymers able to make various self-assembled
      three-dimensional structures that, among other things, use the complementarity
      principle. Here, we review various self-assembled nucleic acid structures as well
      as application of DNA and RNA to develop nanomaterials, molecular automata, and
      nanodevices. It can be expected that in the near future results of these
      developments will allow designing novel next-generation diagnostic systems and
      medicinal drugs. 

PMID- 25869356
TI  - Physiological role of alternative oxidase (from yeasts to plants).
AB  - Mitochondria of all so far studied organisms, with the exception of Archaea,
      mammals, some yeasts, and protists, contain, along with the classical
      phosphorylating cytochrome pathway, a so-called cyanide-insensitive alternative
      oxidase (AOX) localized on the matrix side of the mitochondrial inner membrane,
      and electron transport through which is not coupled with ATP synthesis and energy
      accumulation. Mechanisms underlying plentiful functions of AOX in organisms at
      various levels of organization ranging from yeasts to plants are considered.
      First and foremost, AOX provides a chance of cell survival after inhibiting the
      terminal components of the main respiratory chain or losing the ability to
      synthesize these components. The vitally important role of AOX is obvious in
      thermogenesis of thermogenic plant organs where it becomes the only terminal
      oxidase with a very high activity, and the energy of substrate oxidation by this
      respiratory pathway is converted into heat, thus promoting evaporation of
      volatile substances attracting pollinating insects. AOX plays a fundamentally
      significant role in alleviating or preventing oxidative stress, thus ensuring the
      defense against a wide range of stresses and adverse environmental conditions,
      such as changes in temperature and light intensities, osmotic stress, drought,
      and attack by incompatible strains of bacterial pathogens, phytopathogens, or
      their elicitors. Participation of AOX in pathogen survival during its existence
      inside the host, in antivirus defense, as well as in metabolic rearrangements in
      plants during embryogenesis and cell differentiation is described. Examples are
      given to demonstrate that AOX might be an important tool to overcome the adverse
      aftereffects of restricted activity of the main respiratory chain in cells and
      whole animals. 

PMID- 25869357
TI  - Recombinant horseradish peroxidase: production and analytical applications.
AB  - Horseradish peroxidase is a key enzyme in bio- and immunochemical analysis. New
      approaches in functional expression of the peroxidase gene in E. coli cells and
      the subsequent refolding of the resulting protein yield a recombinant enzyme that
      is comparable in its spectral and catalytic characteristics to the native plant
      peroxidase. Genetic engineering approaches allow production of recombinant
      peroxidase conjugates with both protein antigens and Fab antibody fragments. The
      present article reviews the use of recombinant horseradish peroxidase as the
      marker enzyme in ELISA procedures as well as in amperometric sensors based on
      direct electron transfer. 

PMID- 25869358
TI  - Effect of cationic plastoquinone SkQ1 on electron transfer reactions in
      chloroplasts and mitochondria from pea seedlings.
AB  - Plastoquinone bound with decyltriphenylphosphonium cation (SkQ1) penetrating
      through the membrane in nanomolar concentrations inhibited H2O2 generation in
      cells of epidermis of pea seedling leaves that was detected by the fluorescence
      of 2',7'-dichlorofluorescein. Photosynthetic electron transfer in chloroplasts
      isolated from pea leaves is suppressed by SkQ1 at micromolar concentrations: the
      electron transfer in chloroplasts under the action of photosystem II or I (with
      silicomolybdate or methyl viologen as electron acceptors, respectively) is more
      sensitive to SkQ1 than under the action of photosystem II + I (with ferricyanide
      or p-benzoquinone as electron acceptors). SkQ1 reduced by borohydride is oxidized
      by ferricyanide, p-benzoquinone, and, to a lesser extent, by silicomolybdate, but
      not by methyl viologen. SkQ1 is not effective as an electron acceptor supporting
      O2 evolution from water in illuminated chloroplasts. The data on suppression of
      photosynthetic O2 evolution or consumption show that SkQ1, similarly to phenazine
      methosulfate, causes conversion of the chloroplast redox-chain from non-cyclic
      electron transfer mode to the cyclic mode without O2 evolution. Oxidation of NADH
      or succinate in mitochondria isolated from pea roots is stimulated by SkQ1. 

PMID- 25869359
TI  - pH might play a role in regulating the function of paired amphipathic helices
      domains of human Sin3B by altering structure and thermodynamic stability.
AB  - Human Sin3B (hSin3B), a transcription regulator, is a scaffold protein that binds
      to different transcription factors and regulates transcription. It consists of
      six conserved domains that include four paired amphipathic helices (PAH 1-4),
      histone deacetylase interaction domain (HID), and highly conserved region (HCR).
      Interestingly, the PAH domains of hSin3B are significantly homologous to each
      other, yet each one interacts with a specific set of unique transcription
      factors. Though various partners interacting with hSin3B PAH domains have been
      characterized, there is no structural information available on the individual PAH
      domains of hSin3B. Here we characterize the structure and stability of different
      PAH domains of hSin3B at both nuclear and physiological pH values by using
      different optical probes. We found that the native state structure and stability
      of different PAH domains are different at nuclear pH where hSin3B performs its
      biological function. We also found that PAH2 and PAH3 behave differently at both
      nuclear and physiological pH in terms of native state structure and thermodynamic
      stability, while the structural identity of PAH1 remains unaltered at both pH
      values. The study indicates that the structural heterogeneity of different PAH
      domains might be responsible for having a unique set of interacting transcription
      factors. 

PMID- 25869360
TI  - Identification and biochemical characterization of a new antibacterial and
      antifungal peptide derived from the insect Sphodromantis viridis.
AB  - Antimicrobial peptides are members of the immune system that protect the host
      from infection. In this study, a potent and structurally novel antimicrobial
      peptide was isolated and characterized from praying mantis Sphodromantis viridis.
      This 14-amino acid peptide was purified by RP-HPLC. Tandem mass spectrometry was
      used for sequencing this peptide, and the results showed that the peptide belongs
      to the Mastoparan family. The peptide was named Mastoparan-S. Mastoparan-S
      demonstrated that it has antimicrobial activities against a broad spectrum of
      microorganisms (Gram-positive and Gram-negative bacteria and fungi), and it was
      found to be more potent than common antibiotics such as kanamycin. Mastoparan-S
      showed higher antimicrobial activity against Gram-negative bacteria compared to
      Gram-positive ones and fungi. The minimum inhibitory concentration (MIC) values
      of Mastoparan-S are 15.1-28.3 ug/ml for bacterial and 19.3-24.6 ug/ml for fungal
      pathogens. In addition, this newly described peptide showed low hemolytic
      activity against human red blood cells. The in vitro cytotoxicity of Mastoparan-S
      was also evaluated on monolayer of normal human cells (HeLa) by MTT assay, and
      the results illustrated that Mastoparan-S had significant cytotoxicity at
      concentrations higher than 40 ug/ml and had no any cytotoxicity at the MIC (<=30
      ug/ml). The findings of the present study reveal that this newly described
      peptide can be introduced as an appropriate candidate for treatment of topical
      infection. 

PMID- 25869361
TI  - Supramolecular organization of Hfq-like proteins.
AB  - Bacterial Hfq proteins are structural homologs of archaeal and eukaryotic Sm/Lsm
      proteins, which are characterized by a 5-stranded beta-sheet and an N-terminal
      alpha-helix. Previously, it was shown that archaeal Lsm proteins (SmAP) could
      produce long fibrils spontaneously, in contrast to the Hfq from Escherichia coli
      that could form similar fibrils only after special treatment. The organization of
      these fibrils is significantly different, but the reason for the dissimilarity
      has not been found. In the present work, we studied the process of fibril
      formation by bacterial protein Hfq from Pseudomonas aeruginosa and archaeal
      protein SmAP from Methanococcus jannaschii. Both proteins have high homology with
      E. coli Hfq. We found that Hfq from P. aeruginosa could form fibrils after
      substitutions in the conserved Sm2 motif only. SmAP from M. jannaschii, like
      other archaeal Lsm proteins, form fibrils spontaneously. Despite differences in
      the fibril formation conditions, the architecture of both was similar to that
      described for E. coli Hfq. Therefore, universal nature of fibril architecture
      formed by Hfq proteins is suggested. 

PMID- 25869362
TI  - Proteorhodopsin from Dokdonia sp. PRO95 is a light-driven Na+-pump.
AB  - The gene encoding proteorhodopsin AEX55013 from Dokdonia sp. PRO95 was cloned and
      expressed in Escherichia coli cells. Illumination of the proteorhodopsin
      producing E. coli cells in Na+-containing media resulted in alkalinization of the
      media. This response was accelerated by uncoupler CCCP and inhibited by
      penetrating anion SCN(-). Illumination of the cells in a sodium-free medium (made
      by substituting Na+ with K+) resulted in SCN(-)-stimulated and CCCP-sensitive
      acidification of the medium. Illumination of the proteorhodopsin-containing E.
      coli cells caused CCCP-resistant transmembrane sodium export from these cells. We
      conclude that the proteorhodopsin from the marine flavobacterium Dokdonia sp.
      PRO95 is a primary light-driven Na+-pump. A high level of the heterologous
      production in E. coli cells as well as stability and purity of the isolated
      protein makes this proteorhodopsin an attractive model for studying the mechanism
      of active sodium transmembrane translocation. 

PMID- 25869363
TI  - Coxsackievirus B3 induces viral myocarditis by upregulating toll-like receptor 4
      expression.
AB  - In the present study, we investigated the potential pathogenesis of
      coxsackievirus B3 (CVB3)-induced viral myocarditis and the promising protective
      effect of silencing RNA (small interfering RNA, siRNA). One hundred and twenty
      mice were included in the study, and 30 mice were intraperitoneally inoculated
      with CVB3 to establish an acute viral myocarditis model. The survival rate was
      observed for the CVB3-infected mouse model (MOD), and myocardial injury was
      examined by HE (hematoxylin and eosin) staining assay. Real-time PCR (RT-PCR) and
      Western blot assay were selected to detect the toll-like receptor 4 (TLR4)
      expression in myocardial tissues. The TLR4 gene was silenced for the MOD mice,
      and the effects of this treatment were observed. The results indicate that the
      expression of TLR4 mRNA and the protein significantly and persistently increased
      during the progression of CVB3-induced myocarditis. The activities of cardiac
      enzymes including CK, LDH, AST, and CK-MB were also enhanced in CVB3-induced
      myocardial tissues. Interestingly, when the TLR4 gene was silenced, the CVB3
      induced TLR4 production was significantly decreased and the severity of
      myocarditis was significantly lessened. In conclusion, CVB3 may induce viral
      myocarditis by upregulating toll-like receptor 4 expression. The viral
      myocarditis can be ameliorated by silencing the TLR4 gene in the CVB3 viral
      myocarditis model, which may be a feasible therapeutic method for treatment of
      viral myocarditis. 

PMID- 25869364
TI  - Denaturation properties and folding transition states of leghemoglobin and other
      heme proteins.
AB  - This work reports unfolding transitions of monomeric heme proteins leghemoglobin
      (Lb), myoglobin (Mb), and cytochrome c (Cyt c) utilizing UV-Vis spectral and
      steady-state and time-resolved fluorescence methods. Conformational stabilities
      of the native "folded" state of the proteins and their "unfolded" states were
      investigated in the light of a two-state transition model. Two-state transition
      values for DeltaGD (298K) were obtained by denaturation with the chaotropic
      agents urea and guanidium hydrochloride (GdnHCl). The free energy value of Lb is
      the lowest compared to Cyt c and Mb along the denaturation pathway. The m value
      is also the lowest for Lb compared to Cyt c and Mb. The m value (a measure of
      dependence of DeltaGD on denaturant concentration) for Cyt c and Mb is lower when
      it is denatured with urea compared to GdnHCl. The UV-Vis absorbance maximum and
      steady state fluorescence emission maximum were drastically red shifted in the
      presence of a certain denaturant concentration both in cases of Mb and Lb, but
      the scenario is different for Cyt c. The results are analyzed using a two-state
      transition model. The lifetime data clearly indicate the presence of an
      intermediate state during denaturation. The unfolding transition can modulate the
      conformation, stability, and surface exposure of these biologically important
      proteins. 

PMID- 25869365
TI  - Properties of enzyme preparations and homogeneous enzymes - endoglucanases EG2
      Penicillium verruculosum and LAM Myceliophthora thermophila.
AB  - The genes of endoglucanases EG2 (36.2 kDa) Penicillium verruculosum and LAM (30.8
      kDa) Myceliophthora thermophila were cloned in P. verruculosum recombinant
      strain. New enzyme preparations with highly stable activity against beta-glucan
      and laminarin were obtained and investigated, homogeneous enzymes EG2 (EC
      3.2.1.4) and LAM (EC 3.2.1.6) being purified and characterized. For beta-glucan,
      the EG2 Km value was found to be 10 times higher than that for LAM; however, EG2
      demonstrated greater processivity due to its higher kcat. The pH and temperature
      optima of EG2 and LAM activity against barley beta-glucan overlapped and were 4.3
      4.9 and 61-67 degrees C, respectively, and EG2 appeared to be more stable than
      LAM. Oligosaccharides with degree of polymerization 2-10 were formed by
      hydrolysis of beta-glucan and laminarin by the studied enzymes. The recombinant
      enzyme preparations were faster and more effective in decreasing the reduced
      viscosity of wholegrain barley extract than some commercial enzyme preparations.
      Thus, the new enzyme preparations seem to be rather perspective as feed additives
      for degradation of non-starch polysaccharides in grain animal feed. 

PMID- 25869367
TI  - Alcohol use in films and adolescent alcohol use.
AB  - OBJECTIVES: To investigate whether exposure to alcohol use in films (AUFs) is
      associated with early alcohol use, binge drinking, and alcohol-related problems
      in British adolescents. METHODS: Cross-sectional study with 5163 15-year-olds
      from the Avon Longitudinal Study of Parents and Children in the United Kingdom.
      We measured adolescent exposure to AUFs, age at onset of alcohol use, and binge
      drinking behavior. We adjusted for early childhood social, family and behavioral
      factors, adolescent tobacco use, and peer drinking. RESULTS: After adjustment,
      adolescents with the highest exposure to AUFs were 1.2 (95% confidence interval
      [CI]: 1.1-1.3) times more likely to have tried alcohol compared with those least
      exposed and 1.7 (95% CI: 1.5-2.0) times more likely to binge drink. They were 2.4
      (95% CI: 1.9-3.1) times more likely to drink weekly and 2.0 (95% CI: 1.7-2.4)
      times more likely to have alcohol-related problems than those least exposed.
      CONCLUSIONS: Exposure to AUFs is associated with higher risk of alcohol use and
      alcohol-related problems in UK adolescents. Our findings provide evidence to
      support the argument that a review of film-rating categories and alcohol ratings
      for all films may help reduce problem-related alcohol consumption in young
      people.

PMID- 25869366
TI  - Upregulation of RHOA and NKIRAS1 genes in lung tumors is associated with loss of
      their methylation as well as with methylation of regulatory miRNA genes.
AB  - Methylation of CpG-islands in promoter regions as well as interaction of miRNAs
      with messenger RNAs of target genes are related to multilayer mechanisms
      regulating gene expression. The goal of this study was to assess a possibility
      for miRNA gene methylation to influence indirectly activation of their target
      genes in lung tumors. By using a unified collection of samples of non-small cell
      lung cancer, it was demonstrated that elevated levels of mRNA for RHOA and
      NKIRAS1 genes were significantly (Spearman rank correlation, P < 10(-11))
      associated both with loss of methylation in their CpG-islands and methylation in
      a number of miRNA genes, which, according to the miRWalk database, were predicted
      to possess regulatory functions. Novel potential regulatory miRNAs for RHOA (miR
      9-1/-3, -34b/c, -129-2, -125b-1, -375, -1258) and NKIRAS1 (miR-34b/c, -129-2, 
      125b-1, -193a, -124a-1/-2/-3, -212, -132) genes in lung cancer were identified. 

PMID- 25869368
TI  - Case report of successful treatment of pallid breath-holding spells with
      glycopyrrolate.
AB  - Breath-holding spells are a common childhood disorder that typically present
      before 12 months of age. Whereas most cases are benign, some patients have very
      severe cases associated with bradycardia that can progress from asystole to
      syncope and seizures. Treatment studies have implicated the use of several
      therapies, such as oral iron, fluoxetine, and pacemaker implantation. This is a
      retrospective study of patients treated with glycopyrrolate for pallid breath
      holding spells. Clinical data from 4 patients referred to pediatric cardiology
      who saw therapeutic benefit from treatment using glycopyrrolate were reviewed to
      evaluate for clinical response to the drug. Two twin patients, whose symptoms
      began at 5 months of age, experienced a decrease in breath-holding frequency
      after 1 month. A patient diagnosed at 7 months of age experienced a decrease in
      frequency of spells. A patient diagnosed at 10 months of age reported cessation
      of syncope shortly after initiation of glycopyrrolate and complete resolution of
      breath-holding spells during prolonged treatment. This case study of 4 patients
      with pallid breath-holding offers evidence that glycopyrrolate may be beneficial
      in treating breath-holding spells and has a safer side-effect profile than
      pacemaker implantation. 

PMID- 25869369
TI  - Parenting Skills and Emotional Availability: An RCT.
AB  - OBJECTIVE: To investigate whether a responsive stimulation intervention delivered
      to caregivers of young children either alone or integrated with nutrition
      interventions would benefit parenting skills and emotional availability to
      promote children's development and growth compared with either a nutrition
      intervention alone or the usual standard of care. METHODS: A cluster randomized
      factorial effectiveness trial was implemented in an impoverished community in
      Pakistan. The 4 trial arms were control (usual standard of care), responsive
      stimulation (responsive care and stimulation), enhanced nutrition (education and
      multiple micronutrients), and a combination of both enriched interventions. The 4
      intervention packages were delivered by community health workers to 1489 mother
      infant dyads in the first 2 years of life. Parenting skills and emotional
      availability indexed by mother-child interaction, caregiving environment,
      knowledge and practices pertaining to early childhood care and feeding, and
      maternal depressive symptoms were assessed at multiple intervals. An intention-to
      treat factorial analysis was conducted. RESULTS: Intervention groups were
      comparable at baseline. Responsive stimulation significantly benefitted parenting
      skills with large effect sizes on mother-child interaction (Cohen's d 0.8),
      caregiving environment (Cohen's d 0.9-1.0), and knowledge and practices (Cohen's
      d 0.7-1.1) compared with small-modest significant effects as a result of
      nutrition intervention on mother-child interaction and caregiving environment
      only (Cohen's d 0.4 and 0.2, respectively). The combined intervention had a small
      significant effect on decreasing maternal depressive symptoms over time (Cohen's
      d 0-0.2). CONCLUSIONS: A responsive stimulation intervention can promote positive
      caregiving behaviors among impoverished families. Additional research is needed
      on interventions to reduce maternal depressive symptoms.

PMID- 25869370
TI  - Prescription opioid epidemic and infant outcomes.
AB  - BACKGROUND AND OBJECTIVES: Although opioid pain relievers are commonly prescribed
      in pregnancy, their association with neonatal outcomes is poorly described. Our
      objectives were to identify neonatal complications associated with antenatal
      opioid pain reliever exposure and to establish predictors of neonatal abstinence
      syndrome (NAS). METHODS: We used prescription and administrative data linked to
      vital statistics for mothers and infants enrolled in the Tennessee Medicaid
      program between 2009 and 2011. A random sample of NAS cases was validated by
      medical record review. The association of antenatal exposures with NAS was
      evaluated by using multivariable logistic regression, controlling for maternal
      and infant characteristics. RESULTS: Of 112,029 pregnant women, 31,354 (28%)
      filled >= 1 opioid prescription. Women prescribed opioid pain relievers were more
      likely than those not prescribed opioids (P < .001) to have depression (5.3% vs
      2.7%), anxiety disorder (4.3% vs 1.6%) and to smoke tobacco (41.8% vs 25.8%).
      Infants with NAS and opioid-exposed infants were more likely than unexposed
      infants to be born at a low birth weight (21.2% vs 11.8% vs 9.9%; P < .001). In a
      multivariable model, higher cumulative opioid exposure for short-acting
      preparations (P < .001), opioid type (P < .001), number of daily cigarettes
      smoked (P < .001), and selective serotonin reuptake inhibitor use (odds ratio:
      2.08 [95% confidence interval: 1.67-2.60]) were associated with greater risk of
      developing NAS. CONCLUSIONS: Prescription opioid use in pregnancy is common and
      strongly associated with neonatal complications. Antenatal cumulative
      prescription opioid exposure, opioid type, tobacco use, and selective serotonin
      reuptake inhibitor use increase the risk of NAS.

PMID- 25869371
TI  - Parents' daily time with their children: a workplace intervention.
AB  - OBJECTIVES: In the context of a group randomized field trial, we evaluated
      whether parents who participated in a workplace intervention, designed to
      increase supervisor support for personal and family life and schedule control,
      reported significantly more daily time with their children at the 12-month follow
      up compared with parents assigned to the Usual Practice group. We also tested
      whether the intervention effect was moderated by parent gender, child gender, or
      child age. METHODS: The Support-Transform-Achieve-Results Intervention was
      delivered in an information technology division of a US Fortune 500 company.
      Participants included 93 parents (45% mothers) of a randomly selected focal child
      aged 9 to 17 years (49% daughters) who completed daily telephone diaries at
      baseline and 12 months after intervention. During evening telephone calls on 8
      consecutive days, parents reported how much time they spent with their child that
      day. RESULTS: Parents in the intervention group exhibited a significant increase
      in parent-child shared time, 39 minutes per day on average, between baseline and
      the 12-month follow-up. By contrast, parents in the Usual Practice group averaged
      24 fewer minutes with their child per day at the 12-month follow-up. Intervention
      effects were evident for mothers but not for fathers and for daughters but not
      sons. CONCLUSIONS: The hypothesis that the intervention would improve parents'
      daily time with their children was supported. Future studies should examine how
      redesigning work can change the quality of parent-child interactions and
      activities known to be important for youth health and development.

PMID- 25869372
TI  - Preserving patient privacy and confidentiality in the era of personal health
      records.

PMID- 25869374
TI  - Reducing Cancelations on the Day of Scheduled Surgery at a Children's Hospital.
AB  - BACKGROUND AND OBJECTIVES: Cancelation on the day of surgery (DoSC) represents a
      costly wastage of operating room (OR) time and causes inconvenience, emotional
      distress, and financial cost to families. A quality improvement project sought to
      reduce lost OR time due to cancelation. METHODS: Key drivers of the process
      included effective 2-way communication with families, compliance with fasting
      rules, and decision-making on patient illness before the day of surgery. A
      multidisciplinary team conducted serial tests of change addressing the various
      key drivers. Interventions were simplified, colorful, personalized preoperative
      instruction sheets and text-message reminders to caregivers' cellphones, as well
      as a defined institutional decision-making pathway to permit rescheduling before
      the day of surgery in case of patient illness concerns. After initial smaller
      scale testing, the interventions were implemented across all patients and sites.
      Data were collected from the hospital information technology system and analyzed
      by using control charts and statistical process control methods. RESULTS: Mean OR
      time lost due to DoSC was decreased from a baseline of 5.7 to 3.6 hours/day in
      testing with a subset of surgical services at the hospital's base campus, and
      then from 6.6 hours to 5.5 hours/day when implemented across all services at both
      surgical sites. CONCLUSIONS: By applying quality improvement methods, significant
      reductions were made in time lost due to DoSC. The impact can be significant by
      improving institutional resource utilization.

PMID- 25869373
TI  - Outcomes and costs of surgical treatments of necrotizing enterocolitis.
AB  - BACKGROUND AND OBJECTIVES: Despite previous studies demonstrating no difference
      in mortality or morbidity, the various surgical approaches for necrotizing
      enterocolitis (NEC) in infants have not been evaluated economically. Our goal was
      to compare total in-hospital cost and mortality by using propensity score-matched
      infants treated with peritoneal drainage alone, peritoneal drainage followed by
      laparotomy, or laparotomy alone for surgical NEC. METHODS: Utilizing the
      California OSHPD Linked Birth File Dataset, 1375 infants with surgical NEC
      between 1999 and 2007 were retrospectively propensity score matched according to
      intervention type. Total in-hospital costs were converted from longitudinal
      patient charges. A multivariate mixed effects model compared adjusted costs and
      mortality between groups. RESULTS: Successful propensity score matching was
      performed with 699 infants (peritoneal drainage, n = 101; peritoneal drainage
      followed by laparotomy, n = 172; and laparotomy, n = 426). Average adjusted cost
      for peritoneal drainage followed by laparotomy was $398,173 (95% confidence
      interval [CI]: 287,784-550,907), which was more than for peritoneal drainage
      ($276,076 [95% CI: 196,238-388,394]; P = .004) and similar to laparotomy
      ($341,911 [95% CI: 251,304-465,186]; P = .08). Adjusted mortality was highest
      after peritoneal drainage (56% [95% CI: 34-75]) versus peritoneal drainage
      followed by laparotomy (35% [95% CI: 19-56]; P = .01) and laparotomy (29% [95%
      CI: 19-56]; P < .001). Mortality for peritoneal drainage was similar to
      laparotomy. CONCLUSIONS: Propensity score-matched analysis of surgical NEC
      treatment found that peritoneal drainage followed by laparotomy was associated
      with decreased mortality compared with peritoneal drainage alone but at
      significantly increased costs.

PMID- 25869375
TI  - The medical home and integrated behavioral health: advancing the policy agenda.
AB  - There has been a considerable expansion of the patient-centered medical home
      model of primary care delivery, in an effort to reduce health care costs and to
      improve patient experience and population health. To attain these goals, it is
      essential to integrate behavioral health services into the patient-centered
      medical home, because behavioral health problems often first present in the
      primary care setting, and they significantly affect physical health. At the 2013
      Patient-Centered Medical Home Research Conference, an expert workgroup convened
      to determine policy recommendations to promote the integration of primary care
      and behavioral health. In this article we present these recommendations: Build
      demonstration projects to test existing approaches of integration, develop
      interdisciplinary training programs to support members of the integrated care
      team, implement population-based strategies to improve behavioral health,
      eliminate behavioral health carve-outs and test innovative payment models, and
      develop population-based measures to evaluate integration. 

PMID- 25869376
TI  - The medical home and integrated behavioral health.

PMID- 25869378
TI  - Childhood vaccination coverage rates among military dependents in the United
      States.
AB  - BACKGROUND AND OBJECTIVES: The Military Health System provides universal coverage
      of all recommended childhood vaccinations. Few studies have examined the effect
      that being insured by the Military Health System has on childhood vaccination
      coverage. The purpose of this study was to compare the coverage of the
      universally recommended vaccines among military dependents versus other insured
      and uninsured children using a nationwide sample of children. METHODS: The
      National Immunization Survey is a multistage, random-digit dialing survey
      designed to measure vaccination coverage estimates of US children aged 19 to 35
      months old. Data from 2007 through 2012 were combined to permit comparison of
      vaccination coverage among military dependent and all other children. RESULTS:
      Among military dependents, 28.0% of children aged 19 to 35 months were not up to
      date on the 4:3:1:3:3:1 vaccination series excluding Haemophilus influenzae type
      b vaccine compared with 21.1% of all other children (odds ratio: 1.4; 95%
      confidence interval: 1.2-1.6). After controlling for sociodemographic
      characteristics, compared with all other US children, military dependent children
      were more likely to be incompletely vaccinated (odds ratio: 1.3; 95% confidence
      interval: 1.1-1.5). CONCLUSIONS: Lower vaccination coverage rates among US
      military dependent children might be due to this population being highly mobile.
      However, the lack of a military-wide childhood immunization registry and
      incomplete documentation of vaccinations could contribute to the lower
      vaccination coverage rates seen in this study. These results suggest the need for
      further investigation to evaluate vaccination coverage of children with complete
      ascertainment of vaccination history, and if lower immunization rates are
      verified, assessment of reasons for lower vaccination coverage rates among
      military dependent children.

PMID- 25869377
TI  - Impact of Just-in-Time and Just-in-Place Simulation on Intern Success With Infant
      Lumbar Puncture.
AB  - BACKGROUND AND OBJECTIVE: Simulation-based skill trainings are common; however,
      optimal instructional designs that improve outcomes are not well specified. We
      explored the impact of just-in-time and just-in-place training (JIPT) on interns'
      infant lumbar puncture (LP) success. METHODS: This prospective study enrolled
      pediatric and emergency medicine interns from 2009 to 2012 at 34 centers. Two
      distinct instructional design strategies were compared. Cohort A (2009-2010)
      completed simulation-based training at commencement of internship, receiving
      individually coached practice on the LP simulator until achieving a predefined
      mastery performance standard. Cohort B (2010-2012) had the same training plus
      JIPT sessions immediately before their first clinical LP. Main outcome was LP
      success, defined as obtaining fluid with first needle insertion and <1000 red
      blood cells per high-power field. Process measures included use of analgesia,
      early stylet removal, and overall attempts. RESULTS: A total of 436 first infant
      LPs were analyzed. The LP success rate in cohort A was 35% (13/37), compared with
      38% (152/399) in cohort B (95% confidence interval for difference [CI diff], -15%
      to +18%). Cohort B exhibited greater analgesia use (68% vs 19%; 95% CI diff, 33%
      to 59%), early stylet removal (69% vs 54%; 95% CI diff, 0% to 32%), and lower
      mean number of attempts (1.4 +/- 0.6 vs 2.1 +/- 1.6, P < .01) compared with
      cohort A. CONCLUSIONS: Across multiple institutions, intern success rates with
      infant LP are poor. Despite improving process measures, adding JIPT to training
      bundles did not improve success rate. More research is needed on optimal
      instructional design strategies for infant LP.

PMID- 25869379
TI  - Breastfeeding Assessment Score: Systematic Review and Meta-analysis.
AB  - BACKGROUND: Previous studies have revealed conflicting results for the
      Breastfeeding Assessment Score (BAS) in predicting early breastfeeding cessation.
      Our objective was to externally validate the BAS and provide summary accuracy
      estimates for this clinical prediction model. METHODS: We used the original data
      from a prospective cohort study. Additional studies were identified by searching
      electronic databases (Medline, Embase, Cumulative Index to Nursing and Allied
      Health Literature, and Cochrane) from 2002 to 2013 and contacting research groups
      that had derived or validated the BAS. Prospective cohort studies were eligible
      if the BAS was computed at baseline and mothers were followed up for
      breastfeeding cessation. Two physicians extracted relevant information and
      independently assessed the methodological quality for the included studies.
      RESULTS: In the external validation cohort, 22 of 424 mothers (5.2%) discontinued
      breastfeeding within 14 days of infant age. The BAS predicted early breastfeeding
      cessation with an area under the curve of 0.70 (95% confidence interval [CI]:
      0.65 to 0.74) and inadequate calibration. When restricting the meta-analysis to
      3169 mother-infant pairs enrolled in 4 higher-quality studies, a BAS value <8
      predicted early cessation with 0.80 sensitivity (95% CI: 0.69 to 0.91) and 0.51
      specificity (95% CI: 0.32 to 0.70) summary estimates. CONCLUSIONS: Substantial
      between-study heterogeneity limited the interpretation of summary accuracy
      estimates. The BAS predicts early breastfeeding cessation with moderate accuracy,
      although local recalibration is advised before implementation. Further study is
      warranted to determine whether the BAS can help pediatricians in identifying
      mother-infant pairs that may benefit from more extensive breastfeeding assessment
      and support.

PMID- 25869380
TI  - Mutation rates in plastid genomes: they are lower than you might think.
AB  - Within plastid-bearing species, the mutation rate of the plastid genome is often
      assumed to be greater than that of the mitochondrial genome. This assumption is
      based on early, pioneering studies of land plant molecular evolution, which
      uncovered higher rates of synonymous substitution in plastid versus mitochondrial
      DNAs. However, much of the plastid-containing eukaryotic diversity falls outside
      of land plants, and the patterns of plastid DNA evolution for embryophytes do not
      necessarily reflect those of other groups. Recent analyses of plastid and
      mitochondrial substitution rates in diverse lineages have uncovered very
      different trends than those recorded for land plants. Here, I explore these new
      data and argue that for many protists the plastid mutation rate is lower than
      that of the mitochondrion, including groups with primary or secondary plastids as
      well as nonphotosynthetic algae. These findings have far-reaching implications
      for how we view plastid genomes and how their sequences are used for evolutionary
      analyses, and might ultimately reflect a general tendency toward more efficient
      DNA repair mechanisms in plastids than in mitochondria.

PMID- 25869381
TI  - Identification of Plasmodium falciparum apicoplast-targeted tRNA-guanine
      transglycosylase and its potential inhibitors using comparative genomics,
      molecular modelling, docking and simulation studies.
AB  - tRNA modifications play an important role in the proper folding of tRNA and
      thereby determine its functionality as an adaptor molecule. Notwithstanding the
      centrality of this basic process in translation, a major gap in the genomics of
      Plasmodium falciparum is unambiguous identification of enzymes catalysing the
      various tRNA modifications. In this study, tRNA-modifying enzymes of P.
      falciparum were annotated using homology-based approach. Based on the presence of
      these identified enzymes, the modifications were compared with those of
      prokaryotic and eukaryotic organisms. Through sequence comparison and
      phylogenetic analysis, we have identified P. falciparum apicoplast tRNA-guanine
      34 transglycosylase (TGT, EC: 2.4.2.29), which shows evidence of its prokaryotic
      origin. The docking analysis of the modelled TGT structures revealed that binding
      of quinazolinone derivatives is more favourable with P. falciparum apicoplast TGT
      as compared to human TGT. Molecular dynamic simulation and molecular
      mechanics/generalized Born surface area analysis of the complex confirmed the
      greater binding affinity of the ligand in the binding pocket of P. falciparum TGT
      protein. Further, evolutionary patterning analysis identified the amino acids of
      P. falciparum apicoplast TGT that are under purifying selection pressure and
      hence can be good inhibitor-targeting sites. Based on these computational
      studies, we suggest that P. falciparum apicoplast tRNA-guanine 34
      transglycosylase can be a promising drug target. 

PMID- 25869382
TI  - Efficacy and safety of late-course hypofractionated radiation therapy for muscle
      invasive bladder carcinoma after bladder-conserving surgery.
AB  - AIM: To evaluate the efficacy and safety of late-course hypofractionated
      radiation treatment of muscle-invasive bladder carcinoma after bladder-conserving
      surgery. METHODS: Seventy-six patients with transitional cell bladder carcinoma,
      stage II (T2-4N0M0), after transurethral resection, were enrolled. Pirarubicin
      was given at 30 mg/m2 and 100 mL physiological saline once weekly (QW) for 12
      weeks through and after intravesical instillation postoperatively. Radiation
      schedule delivered 46 Gy in 20 fractions for planning target volume, with an
      additional 20 Gy in five fractions for gross tumor volume as late-course
      radiation. Chemotherapy was stopped if Radiation Therapy Oncology Group grade 3
      or higher bladder or bowel toxicity occurred. The primary end points were acute
      toxicity, local control and patients' survival. RESULTS: One-, three- and five
      year overall survival rates were 98, 78 and 69.5%, respectively. Mean survival
      time was 58.4 months (95% CI: 52.6, 64.2). In addition, 1-, 3- and 5-year local
      control rates were 100, 80.5 and 76.1%, respectively. Mean local control time was
      60.7 months (95% CI: 55.1, 66.3). The cumulative incidence of local/regional
      failure and distant failure was 28.9%. The rate of single local/regional failure
      was 13.2%, but distant failure rate was 21.1%. CONCLUSIONS: Concurrent
      pirarubicin-based late-course hypofractionated radiation therapy showed desirable
      local control rate and acceptable toxicity. It could be used after bladder
      conserving surgery to allow patients to preserve their bladder.

PMID- 25869383
TI  - Horn growth patterns in Alpine chamois.
AB  - The analysis of horn growth may provide important information about the
      allocation of metabolic resources to secondary sexual traits. Depending on the
      selective advantages offered by horn size during intra- and inter-specific
      interactions, ungulates may show different investment in horn development, and
      growth variations within species may be influenced by several parameters, such as
      sex, age, or resource availability. We investigated the horn growth patterns in
      two hunted populations of Alpine chamois (Rupicapra r. rupicapra) in the Central
      Italian Alps. We tested the role of individual heterogeneity on the growth
      pattern and explored the variation in annulus length as a function of different
      factors (sex, age, hunting location, cohort). We then investigated the mechanisms
      underlying horn growth trajectories to test for the occurrence of compensatory or
      recovery growth and their potential differences between sexes and populations.
      Annulus length varied as a function of sex, age of individuals and, marginally,
      hunting location; no effect of cohort or individual heterogeneity was detected.
      Male and female chamois showed compensatory horn growth within the first 51/2
      years of life, though the partial convergence of horn trajectories in chamois
      suggests that this mechanisms would best be described as 'recovery growth'.
      Compensation rates were greater in males than in females, while only compensatory
      growth rates up to 21/2 years of age were different in the two populations.
      Besides confirming the sex- and age-dependent pattern of horn development, our
      study suggests that the mechanism of recovery growth supports the hypothesis of
      horn size as a weakly selected sexual trait in male and female chamois.
      Furthermore, the greater compensation rates in horn growth shown by male chamois
      possibly suggest selective effects of hunting on age at first reproduction, while
      different compensation rates between populations may suggest the occurrence of
      some plasticity in resource allocation to sexual traits in relation to different
      environments. 

PMID- 25869384
TI  - Reactions of green lizards (Lacerta viridis) to major repellent compounds
      secreted by Graphosoma lineatum (Heteroptera: Pentatomidae).
AB  - The chemical defence of Heteroptera is primarily based on repellent secretions
      which signal the potential toxicity of the bug to its predators. We tested the
      aversive reactions of green lizards (Lacerta viridis) towards the major compounds
      of the defensive secretion of Graphosoma lineatum, specifically: (i) a mixture of
      three aldehydes: (E)-hex-2-enal, (E)-oct-2-enal, (E)-dec-2-enal; (ii) a mixture
      of these three aldehydes and tridecane; (iii) oxoaldehyde: (E)-4-oxohex-2-enal;
      (iv) secretion extracted from metathoracic scent glands of G. lineatum adults and
      (v) hexane as a non-polar solvent. All chemicals were presented on a palatable
      food (Tenebrio molitor larvae). The aversive reactions of the green lizards
      towards the mealworms were evaluated by observing the approach latencies, attack
      latencies and approach-attack intervals. The green lizards exhibited a strong
      aversive reaction to the mixture of three aldehydes. Tridecane reduced the
      aversive reaction to the aldehyde mixture. Oxoaldehyde caused the weakest, but
      still significant, aversive reaction. The secretion from whole metathoracic scent
      glands also clearly had an aversive effect on the green lizards. Moreover, when a
      living specimen of G. lineatum or Pyrrhocoris apterus (another aposematic red-and
      black prey) was presented to the green lizards before the trials with the
      aldehyde mixture, the aversive effect of the mixture was enhanced. In conclusion,
      the mixture of three aldehydes had the strong aversive effect and could signal
      the potential toxicity of G. lineatum to the green lizards. 

PMID- 25869385
TI  - The Prognostic Impact of CD163-Positive Macrophages in Follicular Lymphoma: A
      Study from the BC Cancer Agency and the Lymphoma Study Association.
AB  - PURPOSE: We aimed to assess the prognostic significance of follicular lymphoma
      associated macrophages in the era of rituximab treatment and maintenance.
      EXPERIMENTAL DESIGN: We applied immunohistochemistry for CD68 and CD163 to two
      large tissue microarrays (TMA). The first TMA included samples from 186 patients
      from the BC Cancer Agency (BCCA) who had been treated with first-line systemic
      treatment including rituximab, cyclophosphamide, vincristine, and prednisone. The
      second contained 395 samples from PRIMA trial patients treated with rituximab,
      cyclophosphamide, doxorubicin, vincristine, and prednisone, and randomized to
      rituximab maintenance or observation. Macrophage infiltration was assessed using
      Aperio image analysis. Each of the two cohorts was randomly split into
      training/validation sets. RESULTS: An increased CD163-positive pixel count was
      predictive of adverse outcome in the BCCA dataset [5-year progression-free
      survival (PFS) 38% vs. 72%, respectively, P = 0.004 in the training cohort and 5
      year PFS 29% vs. 61%, respectively, P = 0.004 in the validation cohort]. In the
      PRIMA trial, an increased CD163 pixel count was associated with favorable outcome
      (5-year PFS 60% vs. 44%, respectively, P = 0.011 in the training cohort and 5
      year PFS 55% vs. 37%, respectively, P = 0.030 in the validation cohort).
      CONCLUSIONS: CD163-positive macrophages predict outcome in follicular lymphoma,
      but their prognostic impact is highly dependent on treatment received.

PMID- 25869386
TI  - A New B7:CD28 Family Checkpoint Target for Cancer Immunotherapy: HHLA2.
AB  - HHLA2 is a newly identified B7 family member that modulates T-cell functions
      through interaction with TMIGD2 and possibly a second receptor, with coinhibition
      in two studies and costimulation in one study. HHLA2 is expressed on a variety of
      human cancers, and its coinhibitory function makes it a candidate for cancer
      immunotherapy.

PMID- 25869387
TI  - Ablative Tumor Radiation Can Change the Tumor Immune Cell Microenvironment to
      Induce Durable Complete Remissions.
AB  - PURPOSE: The goals of the study were to elucidate the immune mechanisms that
      contribute to desirable complete remissions of murine colon tumors treated with
      single radiation dose of 30 Gy. This dose is at the upper end of the ablative
      range used clinically to treat advanced or metastatic colorectal, liver, and non
      small cell lung tumors. EXPERIMENTAL DESIGN: Changes in the tumor immune
      microenvironment of single tumor nodules exposed to radiation were studied using
      21-day (>1 cm in diameter) CT26 and MC38 colon tumors. These are well
      characterized weakly immunogenic tumors. RESULTS: We found that the high-dose
      radiation transformed the immunosuppressive tumor microenvironment resulting in
      an intense CD8(+) T-cell tumor infiltrate, and a loss of myeloid-derived
      suppressor cells (MDSC). The change was dependent on antigen cross-presenting
      CD8(+) dendritic cells, secretion of IFNgamma, and CD4(+)T cells expressing
      CD40L. Antitumor CD8(+) T cells entered tumors shortly after radiotherapy,
      reversed MDSC infiltration, and mediated durable remissions in an IFNgamma
      dependent manner. Interestingly, extended fractionated radiation regimen did not
      result in robust CD8(+) T-cell infiltration. CONCLUSIONS: For immunologically
      sensitive tumors, these results indicate that remissions induced by a short
      course of high-dose radiotherapy depend on the development of antitumor immunity
      that is reflected by the nature and kinetics of changes induced in the tumor cell
      microenvironment. These results suggest that systematic examination of the tumor
      immune microenvironment may help in optimizing the radiation regimen used to
      treat tumors by adding a robust immune response.

PMID- 25869388
TI  - Physician report cards and implementing standards of practice are both
      significantly associated with improved screening colonoscopy quality.
AB  - OBJECTIVES: Adenoma-detection rates (ADRs) are associated with decreased interval
      colorectal cancer (CRC) rates and CRC mortality; quality improvement strategies
      focus on improving physician ADRs. The objective of this study was to examine the
      sequential effect of physician report cards and implementing institutional
      standards of practice (SOP) on ADRs. METHODS: Colonoscopy metrics were
      prospectively evaluated at a single academic medical center over a 23-month
      period (November 2012 to October 2014). ADRs were evaluated over three time
      periods-Period 1: Before initial report card distribution or SOP (November 2012
      to March 2013); Period 2: After individualized report card distribution detailing
      physician and institutional ADRs (April 2013 to March 2014); Period 3: After
      second report card and SOP implementation (April 2014 to October 2014). The SOP
      required physicians to have a minimum 5-min withdrawal time in normal
      colonoscopies (WT) and an ADR minimum of 20%; those who did not meet benchmarks
      would require further training or endoscopy block time alterations. Only
      endoscopists averaging >15 colonoscopies/month were included in this analysis.
      RESULTS: Twenty endoscopists met the inclusion criteria, performing 12,894
      screening colonoscopies over the 23-month period. Following report card
      distribution, physician ADRs increased by 3% (P<0.001). SOP implementation
      resulted in a further significant increase in mean physician ADR of 8%
      (P<0.0001). Overall, mean ADR increased by 11% from Period 1 to Period 3
      (P<0.0001). All physicians met the minimum 20% ADR benchmark during Period 3.
      Although ADRs significantly correlated with WT overall (r=0.45; 95% CI 0.01,
      0.75; P=0.04), mean WT did not significantly increase from Period 1 to Period 3.
      CONCLUSIONS: Our data suggest that distributing colonoscopy quality report cards
      resulted in a significant ADR improvement. Further, we report evidence that
      implementing SOP significantly improved ADRs beyond report card distribution and
      resulted in all endoscopists meeting minimum benchmarks. This suggests that
      report cards and SOPs may have an additive effect in improving colonoscopy
      quality, and their implementation in endoscopy labs should be encouraged.

PMID- 25869389
TI  - Oral prolonged release beclomethasone dipropionate and prednisone in the
      treatment of active ulcerative colitis: results from a double-blind, randomized,
      parallel group study.
AB  - OBJECTIVES: Double-blind study comparing efficacy and safety of the topically
      acting corticosteroid beclomethasone dipropionate (BDP) to prednisone (PD) in
      patients with active, mild-to-moderate ulcerative colitis (UC). METHODS: Overall,
      282 patients were randomized to receive BDP-prolonged release tablets 5 mg once
      daily for 4 weeks and then every other day for an additional 4 weeks or oral PD
      40 mg once daily for the initial 2 weeks tapered of 10 mg every 2 weeks during
      the 8-week study period. Efficacy end point was the non-inferiority of BDP vs. PD
      in terms of Disease Activity Index (DAI) score <3 or reduction by at least 3
      points for patients with a baseline DAI >=7 at week 4. Safety end point was the
      proportion of patients with steroid-related adverse events (AEs) and cortisol
      <150 nmol/l at week 4. RESULTS: DAI response rates at week 4 were 64.6% and 66.2%
      with BDP and PD, respectively, demonstrating non-inferiority of BDP vs. PD
      (delta: -1.56; 95% confidence interval (CI) -13.00-9.88, P=0.78). Patients with
      steroid-related AEs and cortisol <150 nmol/l at week 4 were 38.7% in the BDP
      group and 46.9% in the PD group (P=0.17 between groups). No safety signals were
      observed in both the groups. CONCLUSIONS: BDP was non-inferior to PD in the
      treatment of active UC, with a good safety profile in both the groups.

PMID- 25869391
TI  - ACG Clinical Guideline: Primary Sclerosing Cholangitis.
AB  - Primary sclerosing cholangitis is a chronic cholestatic liver disease that can
      shorten life and may require liver transplantation. The cause is unknown,
      although it is commonly associated with colitis. There is no approved or proven
      therapy, although ursodeoxycholic acid is used by many on an empiric basis.
      Complications including portal hypertension, fat-soluble vitamin deficiency,
      metabolic bone diseases, and development of cancers of the bile duct or colon can
      occur. 

PMID- 25869394
TI  - Some Like it Hot: Cardioprotective Effect of Curcumin in Chronic Kidney Disease :
      Editorial to: "Cardioprotection by Curcumin Post-Treatment in Rats with
      Established Chronic Kidney Disease" by S. Hernandez-Resendiz et al.

PMID- 25869392
TI  - Alpha-Fetoprotein Measurement Benefits Hepatocellular Carcinoma Surveillance in
      Patients with Cirrhosis.
AB  - OBJECTIVES: Liver cirrhosis is a major risk factor for hepatocellular carcinoma
      (HCC), and all liver study societies recommend HCC surveillance in patients with
      cirrhosis. However, no ideal modality for HCC surveillance has been determined.
      The aim of this study is to assess the effectiveness of alpha-fetoprotein (AFP)
      measurement in HCC surveillance. METHODS: In this retrospective analysis, all
      patients with cirrhosis, who received HCC surveillance through ultrasound (US)
      and AFP measurement between January 2002 and July 2010, were followed up until
      June 2013. The performance effectiveness of surveillance using AFP, US, or both
      in HCC detection was compared. RESULTS: Overall, 1,597 patients were followed for
      a median duration of 4.75 (range 1.42-12) years. Over the 8563.25-person-year
      follow-up period, 363 patients (22.7%) developed HCCs. For HCC detection, the
      area under the receiver operator characteristic curve of surveillance AFP was
      0.844 (95% confidence interval: 0.820-0.868, P<0.001). When the traditional
      cutoff value of 20 ng/ml was used, the sensitivity and specificity of AFP were
      52.9% and 93.3%, respectively. US exhibited a sensitivity and specificity of
      92.0% and 74.2%, respectively. A combination of US and AFP exhibited a
      sensitivity and specificity of 99.2% and 68.3%, respectively. By using cut-off at
      20 ng/ml and AFP level increase >=2 * from its nadir during the previous 1 year,
      the combination of US and AFP yielded a sensitivity of 99.2% and an improved
      specificity of 71.5%. CONCLUSIONS: The complementary use of AFP and US improved
      the effectiveness of HCC surveillance in patients with cirrhosis.

PMID- 25869393
TI  - A randomized, double-blind, placebo-controlled, phase 3 trial to evaluate the
      efficacy, safety, and tolerability of prucalopride in men with chronic
      constipation.
AB  - OBJECTIVES: Prucalopride is effective at alleviating symptoms of chronic
      constipation in women. The aim of this study was to assess the efficacy of 12
      weeks of prucalopride treatment compared with placebo in men with chronic
      constipation. METHODS: This was a multicenter, stratified, randomized, parallel
      group, double-blind, placebo-controlled, phase 3 study (ClinicalTrials.gov
      identifier: NCT01147926). The primary end point was the proportion of patients
      with a mean of three or more spontaneous complete bowel movements (SCBMs) per
      week across the treatment period. Efficacy end points were assessed using daily
      electronic diaries, global assessment of the severity of constipation and
      efficacy of treatment, and Patient Assessment of Constipation-Symptoms (PAC-SYM)
      and Patient Assessment of Constipation-Quality of Life (PAC-QOL) questionnaires.
      RESULTS: In total, 374 patients were enrolled in the study. Significantly more
      patients achieved a mean of three or more SCBMs per week in the prucalopride
      group (37.9%) than in the placebo group (17.7%, P<0.0001). The proportion of
      patients rating their constipation treatment as "quite a bit" to "extremely"
      effective at the final on-treatment visit was 46.7 and 30.4% in the prucalopride
      and placebo groups, respectively. The difference between treatment groups was
      statistically significant (P<0.0001). The proportion of patients with an
      improvement of at least 1 point in PAC-QOL satisfaction subscale score was 52.7
      and 38.8% in the prucalopride and placebo groups, respectively (P=0.0035).
      Prucalopride had a good safety profile and was well tolerated. CONCLUSIONS:
      Prucalopride is effective, has a good safety profile, and is well tolerated for
      the treatment of men with chronic constipation.

PMID- 25869390
TI  - BOB CAT: A Large-Scale Review and Delphi Consensus for Management of Barrett's
      Esophagus With No Dysplasia, Indefinite for, or Low-Grade Dysplasia.
AB  - OBJECTIVES: Barrett's esophagus (BE) is a common premalignant lesion for which
      surveillance is recommended. This strategy is limited by considerable variations
      in clinical practice. We conducted an international, multidisciplinary,
      systematic search and evidence-based review of BE and provided consensus
      recommendations for clinical use in patients with nondysplastic, indefinite, and
      low-grade dysplasia (LGD). METHODS: We defined the scope, proposed statements,
      and searched electronic databases, yielding 20,558 publications that were
      screened, selected online, and formed the evidence base. We used a Delphi
      consensus process, with an 80% agreement threshold, using GRADE (Grading of
      Recommendations Assessment, Development and Evaluation) to categorize the quality
      of evidence and strength of recommendations. RESULTS: In total, 80% of
      respondents agreed with 55 of 127 statements in the final voting rounds.
      Population endoscopic screening is not recommended and screening should target
      only very high-risk cases of males aged over 60 years with chronic uncontrolled
      reflux. A new international definition of BE was agreed upon. For any degree of
      dysplasia, at least two specialist gastrointestinal (GI) pathologists are
      required. Risk factors for cancer include male gender, length of BE, and central
      obesity. Endoscopic resection should be used for visible, nodular areas.
      Surveillance is not recommended for <5 years of life expectancy. Management
      strategies for indefinite dysplasia (IND) and LGD were identified, including a de
      escalation strategy for lower-risk patients and escalation to intervention with
      follow-up for higher-risk patients. CONCLUSIONS: In this uniquely large consensus
      process in gastroenterology, we made key clinical recommendations for the
      escalation/de-escalation of BE in clinical practice. We made strong
      recommendations for the prioritization of future research.

PMID- 25869395
TI  - Catalytic catechol oxidation by copper complexes: development of a structure
      activity relationship.
AB  - A large library of Cu(II) complexes with mononucleating and dinucleating ligands
      was synthesized to investigate their potential as catalysts for the catalytic
      oxidation of 3,5-di-tert-butylcatechol (3,5-DTBC). X-ray structure determination
      for a number of these complexes revealed relatively large Cu...Cu distances and
      the formation of polymeric species. Comparison of the 3,5-DTBC oxidation rates
      showed that ligands that stabilize the biomimetic dinuclear Cu(II) MU-thiolate
      complex also result in copper compounds that are much more active in the
      oxidation of 3,5-DTBC. This oxidation activity is however inhibited by the
      presence of chloride ions. The highest kcat that was observed was 6900 h(-1),
      which is one of the highest turnover frequencies reported so far for catechol
      oxidation in CH3CN.

PMID- 25869396
TI  - Profound blockade of T cell activation requires concomitant inhibition of
      different class I PI3K isoforms.
AB  - PI3K inhibitors have emerged as potential therapeutic tools for a variety of
      diseases, and thus, a vast array of compounds with specificity for different PI3K
      isoforms is being developed. Gaining knowledge about the contribution of the
      different isoforms to PI3K function will allow selecting the most appropriate
      inhibitor for each pathology. In this study, we have addressed the effect of PI3K
      inhibitors with specificity for different class I PI3K isoforms on primary human
      T cell activation. In particular, we have analyzed proliferation, expression of
      activation and differentiation markers, apoptosis induction, cytokine secretion
      and Akt phosphorylation in T cells stimulated in vitro with anti-CD3 and anti
      CD28 monoclonal antibodies and cultured with either one of these compounds:
      p110beta-specific inhibitor TGX-221, p110delta-specific inhibitor IC-87114,
      p110gamma inhibitor AS-242525 or pan-class I PI3K inhibitor BKM120. Inhibition of
      any of the isoforms led to an impairment of T cell activation, mainly of cytokine
      secretion and granzyme B expression. However, only complete blockade of class I
      PI3K activity with the pan-class I inhibitor effectively abrogated T cell
      proliferation. These results indicate that these three p110 isoforms (beta, delta
      and gamma) take part in T cell activation, but all of them are dispensable for T
      cell proliferation.

PMID- 25869398
TI  - Activin-betaC modulates gonadal, but not adrenal tumorigenesis in the inhibin
      deficient mice.
AB  - Activins and inhibins are involved in the regulation of several biological
      processes, including reproduction, development and fertility. Deregulation of the
      inhibin/activin signaling pathway has been implicated in the progression of
      reproductive and adrenal cancers. Deletion of the inhibin alpha-subunit results
      in up-regulation of the circulating levels of activins and this leads to the
      development of sex-cord stromal tumors followed by a cancer associated-cachexia
      in mice. When gonadectomy is performed, development of adrenocortical carcinomas
      is observed. We previously showed that overexpression of activin-betaC modulates
      the development of sex-cord stromal tumors and reduces cancer-cachexia in the
      inhibin-deficient mice by antagonizing the activin signaling pathway. The adrenal
      cortex and gonads share in common a large subset of genes, consistent with their
      common embryonic lineage. Additionally, it has been shown that adrenocortical
      carcinomas adopt an altered cellular identity resembling the ovary. Therefore, a
      study to assess the impact of overexpression of activin-betaC on the onset of
      adrenocortical carcinoma in gonadectomized inhibin-deficient mice was warranted.
      Within the current study we evaluated markers of apoptosis, proliferation, tumor
      burden, survival analysis and serum levels of activin-A in gonadectomized mice
      versus sham operated controls. Results showed that overexpression of activin
      betaC modulated the development of reproductive tumors but had no effect on
      adrenal tumorigenesis. Our data reinforces the importance of activin-betaC in
      reproductive biology and suggest that activin-betaC is a tumor modulator with
      gonadal specificity. 

PMID- 25869397
TI  - Optimizing nanodiscs and bicelles for solution NMR studies of two beta-barrel
      membrane proteins.
AB  - Solution NMR spectroscopy has become a robust method to determine structures and
      explore the dynamics of integral membrane proteins. The vast majority of previous
      studies on membrane proteins by solution NMR have been conducted in lipid
      micelles. Contrary to the lipids that form a lipid bilayer in biological
      membranes, micellar lipids typically contain only a single hydrocarbon chain or
      two chains that are too short to form a bilayer. Therefore, there is a need to
      explore alternative more bilayer-like media to mimic the natural environment of
      membrane proteins. Lipid bicelles and lipid nanodiscs have emerged as two
      alternative membrane mimetics that are compatible with solution NMR spectroscopy.
      Here, we have conducted a comprehensive comparison of the physical and
      spectroscopic behavior of two outer membrane proteins from Pseudomonas
      aeruginosa, OprG and OprH, in lipid micelles, bicelles, and nanodiscs of five
      different sizes. Bicelles stabilized with a fraction of negatively charged lipids
      yielded spectra of almost comparable quality as in the best micellar solutions
      and the secondary structures were found to be almost indistinguishable in the two
      environments. Of the five nanodiscs tested, nanodiscs assembled from
      MSP1D1DeltaH5 performed the best with both proteins in terms of sample stability
      and spectral resolution. Even in these optimal nanodiscs some broad signals from
      the membrane embedded barrel were severely overlapped with sharp signals from the
      flexible loops making their assignments difficult. A mutant OprH that had two of
      the flexible loops truncated yielded very promising spectra for further
      structural and dynamical analysis in MSP1D1DeltaH5 nanodiscs. 

PMID- 25869399
TI  - T(3) rapidly regulates several steps of alpha subunit glycoprotein (CGA)
      synthesis and secretion in the pituitary of male rats: Potential repercussions on
      TSH, FSH and LH secretion.
AB  - TSH, FSH and LH share the same glycoprotein alpha chain (CGA) as part of their
      protein structure. Therefore, it is possible that thyroid and gonadal dysfunction
      may affect the CGA expression. This study evaluated several steps of CGA
      synthesis and secretion in thyrotrophs and gonadotrophs of control and
      hypothyroid rats, acutely or chronically-treated with T3. Hypothyroidism
      increased the Cga mRNA expression and its association to ribosome, but decreased
      intracellular CGA content. These parameters were reversed after acute or chronic
      T3 treatment. We conclude that T3 not only down-regulates Cga mRNA expression, as
      expected, but also inhibits the association of Cga mRNA to ribosome, as well as
      the CGA secretion. These findings add novel insights into our understanding of
      the role of T3 on the regulation of the Cga gene expression and CGA secretion,
      which might have a potential repercussion in all pituitary glycoprotein hormone
      synthesis and secretion. 

PMID- 25869400
TI  - c-Src/Pyk2/EGFR/PI3K/Akt/CREB-activated pathway contributes to human
      cardiomyocyte hypertrophy: Role of COX-2 induction.
AB  - Thrombin and COX-2 regulating cardiac hypertrophy are via various signaling
      cascades. Several transcriptional factors including CREB involve in COX-2
      expression. However, the interplay among thrombin, CREB, and COX-2 in primary
      human neonatal ventricular cardiomyocytes remains unclear. In this study,
      thrombin-induced COX-2 promoter activity, mRNA and protein expression, and PGE2
      synthesis were attenuated by pretreatment with the inhibitors of c-Src (PP1),
      Pyk2 (PF431396), EGFR (AG1478), PI3K/Akt (LY294002/SH-5), and p300 (GR343), or
      transfection with siRNAs of c-Src, Pyk2, EGFR, p110, Akt, CREB, and p300.
      Moreover, thrombin-stimulated phosphorylation of c-Src, Pyk2, EGFR, Akt, CREB and
      p300 was attenuated by their respective inhibitors. These results indicate that
      thrombin-induced COX-2 expression is mediated through PAR-1/c
      Src/Pyk2/EGFR/PI3K/Akt linking to CREB and p300 cascades. Functionally, thrombin
      induced hypertrophy and ANF/BNP release were, at least in part, mediated through
      a PAR-1/COX-2-dependent pathway. We uncover the importance of COX-2 regarding
      human cardiomyocyte hypertrophy that will provide a therapeutic intervention in
      cardiovascular diseases. 

PMID- 25869401
TI  - Use of Type III procollagen measurement as predictor of lung fibroproliferation
      in ARDS: early measurement for earlier antifibroproliferative therapy?

PMID- 25869402
TI  - Impact on outcome of delayed intubation with high-flow nasal cannula oxygen: is
      the device solely responsible?

PMID- 25869403
TI  - Primum non nocere and challenging conventional treatment.

PMID- 25869404
TI  - Feasibility and utility of the use of real time random safety audits in adult ICU
      patients: a multicentre study.
AB  - PURPOSE: The two aims of this study were first to analyse the feasibility and
      utility (to improve the care process) of implementing a new real time random
      safety tool and second to explore the efficacy of this tool in core hospitals
      (those participating in tool design) versus non-core hospitals. METHODS: This was
      a prospective study conducted over a period of 4 months in six adult intensive
      care units (two of which were core hospitals). Safety audits were conducted 3
      days per week during the entire study period to determine the efficacy of the 37
      safety measures (grouped into ten blocks). In each audit, 50% of patients and 50%
      of measures were randomized. Feasibility was calculated as the proportion of
      audits completed over those scheduled and time spent, and utility was defined as
      the changes in the care process resulting from tool application. RESULTS: A total
      of 1323 patient-days were analysed. In terms of feasibility, 87.6% of the
      scheduled audits were completed. The average time spent per audit was 34.5 +/- 29
      min. Globally, changes in the care process occurred in 5.4% of the measures
      analysed. In core hospitals, utility was significantly higher in 16 of the 37
      measures, all of which were included in good clinical practice guidelines. Most
      of the clinical changes brought about by the tool occurred in the mechanical
      ventilation and haemodynamics blocks. Multivariate analyses demonstrated that
      changes in the care process in each block were associated with the core hospital
      variable, staffing ratios and severity of patient disease. CONCLUSIONS: Real time
      safety audits improved the care process and adherence to the clinical practice
      guidelines and proved to be most useful in situations of high care load and in
      patients with more severe disease. The effect was greater in core hospitals.

PMID- 25869405
TI  - High-flow nasal cannula oxygen during endotracheal intubation in hypoxemic
      patients: a randomized controlled clinical trial.
AB  - PURPOSE: Intubation of hypoxemic patients is associated with life-threatening
      adverse events. High-flow therapy by nasal cannula (HFNC) for preoxygenation
      before intubation has never been assessed by randomized study. Our objective was
      to evaluate the efficiency of HFNC for preoxygenation, compared to high fraction
      inspired oxygen facial mask (HFFM). METHODS: Multicenter, randomized, open
      labelled, controlled PREOXYFLOW trial (NCT 01747109) in six French intensive care
      units. Acute hypoxemic adults requiring intubation were randomly allocated to
      HFNC or HFFM. Patients were eligible if PaO2/FiO2 ratio was below 300 mmHg,
      respiratory rate at least 30/min and if they required FiO2 50% or more to obtain
      at least 90% oxygen saturation. HFNC was maintained throughout the procedure,
      whereas HFFM was removed at the end of general anaesthesia induction. Primary
      outcome was the lowest saturation throughout intubation procedure. Secondary
      outcomes included adverse events related to intubation, duration of mechanical
      ventilation and death. RESULTS: A total of 124 patients were randomized. In the
      intent-to-treat analysis, including 119 patients (HFNC n = 62; HFFM n = 57), the
      median (interquartile range) lowest saturation was 91.5% (80-96) for HFNC and
      89.5% (81-95) for the HFFM group (p = 0.44). There was no difference for
      difficult intubation (p = 0.18), intubation difficulty scale, ventilation-free
      days (p = 0.09), intubation-related adverse events including desaturation <80% or
      mortality (p = 0.46). CONCLUSIONS: Compared to HFFM, HFNC as a preoxygenation
      device did not reduce the lowest level of desaturation.

PMID- 25869406
TI  - Breast Cancer Screening Among Dominican Latinas: A Closer Look at Fatalism and
      Other Social and Cultural Factors.
AB  - With the marked increase of the Latino population in the United States during the
      past 20 years, there has been growing interest in the social, cultural, and
      structural factors that may impede breast cancer screening among Latino women,
      especially among those subgroups that have been understudied. Acculturation and
      fatalism are central cultural constructs in these growing fields of research.
      However, there is great debate on the extent to which acculturation and fatalism
      affect breast cancer screening among Latinas relative to other social or
      structural factors or logistical barriers. Moreover, little theoretical work
      specifies or tests pathways between social, structural, and cultural determinants
      of screening. This study tests a theoretical model of social and structural
      (socioeconomic status and access to health care) and cultural factors
      (acculturation and fatalism) as correlates of mammography screening among
      Dominican Latinas, a group that has been understudied. The study expands prior
      work by examining other factors identified as potential impediments to
      mammography screening, specifically psychosocial (e.g., embarrassment, pain) and
      logistical (e.g., not knowing how to get a mammogram, cost) barriers. Interview
      administered surveys were conducted with 318 Latinas from the Dominican Republic
      aged 40 years or older. Fatalistic beliefs were not associated with mammogram
      screening. Greater acculturation assessed as language use was associated with
      decreased screening. The strongest predictor of decreased screening was perceived
      barriers. Results highlight the importance of assessing various self-reported
      psychosocial and logistical barriers to screening. Possible avenues for screening
      interventions include intensifying public health campaigns and use of
      personalized messages to address barriers to screening. Results add to a limited
      body of research on Dominicans, who constitute the fifth largest Latino group in
      the United States. 

PMID- 25869407
TI  - Evaluation of Intervention Reach on a Citywide Health Behavior Change Campaign:
      Cross-Sectional Study Results.
AB  - Little is known about dissemination strategies that contribute to health
      information recognition. This study examined (a) health campaign exposure and
      awareness (slogan and logo recognition); (b) perceived communication channels;
      (c) differences between perceptions of researcher-developed and enhancement
      community health information materials; and (d) differences in campaign awareness
      and communication channels, according to Japanese community demographic
      characteristics. A cross-sectional survey (N = 508) was conducted in Tokigawa,
      Japan, in 2013. The Small Change Campaign focused on increasing physical activity
      and improving dietary habits. Information dissemination was carried out using
      leaflets, newsletters, posters, website, local public relations magazines, health
      classes, events, and online newsletters. The participants completed a survey
      assessing their campaign awareness (i.e., slogan and logo) and exposure to the
      informational materials presented during the campaign. Fewer than half (45.4%)
      knew the slogan, and only 24.4% were aware of the logo. Public relations
      magazines, leaflets, and newsletters were significantly better-perceived health
      communication channels. Researcher-developed and enhancement community health
      information materials were equally recognized (p = .34, w = .08). Furthermore,
      women and those who were employed were significantly more aware of the slogan,
      logo, and communication materials. Further research should explore effective
      communication strategies for community-based health promotion intervention via
      randomized control trials. 

PMID- 25869409
TI  - Letter to the editor regarding: "Novel frame-shift mutations of GLI3 gene in non
      syndromic postaxial polydactyly patients" Clinica Chimica acta 433 (2014) 195
      199.

PMID- 25869408
TI  - American association of clinical endocrinologists and american college of
      endocrinology - clinical practice guidelines for developing a diabetes mellitus
      comprehensive care plan - 2015.

PMID- 25869410
TI  - [Severe delayed bleeding during bridging therapy after abdominal surgery in the
      elderly].

PMID- 25869411
TI  - [Soft tissue tumours: The dreaded sarcoma].

PMID- 25869412
TI  - [Aortic stenosis and iron deficiency anaemia of unclear cause: Heyde's
      syndrome?].

PMID- 25869413
TI  - Peripheral mononuclear blood cells contribute to the obesity-associated
      inflammatory state independently of glycemic status: involvement of the novel
      proinflammatory adipokines chemerin, chitinase-3-like protein 1, lipocalin-2 and
      osteopontin.
AB  - Inflammation is a critical contributor to the pathogenesis of metabolic disorders
      with adipose tissue being crucial in the inflammatory response by releasing
      multiple adipokines with either pro- or anti-inflammatory activities with
      potential functions as metabolic regulators. Peripheral blood mononuclear cells
      (PBMC) have been proposed as representative of the inflammatory status in
      obesity. The aim of the present study was to evaluate the contribution of PBMC to
      the obesity-associated chronic inflammation analyzing the expression of novel
      adipokines. Samples obtained from 69 subjects were used in the study. Real-time
      PCR determinations were performed to quantify gene expression levels in PBMC of
      novel adipokines including chemerin, chitinase-3-like protein 1 (YKL-40),
      lipocalin-2 (LCN-2) and osteopontin (OPN), and their circulating concentrations
      were also determined by ELISA. We show, for the first time, that PBMC gene
      expression levels of chemerin (P < 0.0001), chitinase-3-like protein 1 (P =
      0.010), lipocalin-2 (P < 0.0001) and osteopontin (P < 0.0001) were strongly
      upregulated in obesity independently of the glycemic state. Circulating
      concentrations of these adipokines followed the same trend being significantly
      higher (P < 0.05) in obese normoglycemic and type 2 diabetic patients compared to
      lean volunteers and also associated (P < 0.05) with their corresponding mRNA
      levels in PBMC. These results provide evidence that alterations in inflammation
      related adipokines are manifest in PBMC, which might contribute to the low-grade
      chronic inflammation that characterizes obesity. 

PMID- 25869414
TI  - Serum Levels of Copper and Zinc in Patients with Rheumatoid Arthritis: a Meta
      analysis.
AB  - Many publications with conflicting results have evaluated serum levels of copper
      (Cu) and zinc (Zn) in patients with rheumatoid arthritis (RA). To derive a more
      precise estimation of the relationship, a meta-analysis was conducted. Relevant
      published data were retrieved through PubMed, Chinese National Knowledge
      Infrastructure (CNKI), and Chinese Biomedical Database (CBM) before September 20,
      2014. Weighted mean difference (WMD) with a 95 % confidence interval (95 % CI)
      was calculated using STATA 11.0. A total of 26 studies, including 1444 RA cases
      and 1241 healthy controls, were collected in this meta-analysis. Pooled analysis
      found that patients with RA had a higher serum level of Cu and a lower serum Zn
      level than the healthy controls (Cu (MUg/dl), WMD = 31.824, 95 % CI = 20.334,
      43.314; Zn (MUg/dl), WMD = -12.683, 95 % CI = -19.783, -5.584). Subgroup analysis
      showed that ethnicity had influence on the serum level of Cu (MUg/dl) (Caucasian,
      WMD = 43.907, 95 % CI = 35.090, 52.723, P < 0.001; Asian, WMD = 14.545, 95 % CI =
      -12.365, 41.455, P = 0.289) and Zn (MUg/dl) (Caucasian, WMD = -11.038, 95 % CI = 
      23.420, 1.344, P = 0.081; Asian, WMD = -14.179, 95 % CI = -18.963, -9.394, P <
      0.001) in RA and healthy controls. No evidence of publication bias was observed.
      This meta-analysis suggests that increased serum level of Cu and decreased serum
      level of Zn are generally present in RA patients. 

PMID- 25869415
TI  - Multi-focus cluster labeling.
AB  - Document collections resulting from searches in the biomedical literature, for
      instance, in PubMed, are often so large that some organization of the returned
      information is necessary. Clustering is an efficient tool for organizing search
      results. To help the user to decide how to continue the search for relevant
      documents, the content of each cluster can be characterized by a set of
      representative keywords or cluster labels. As different users may have different
      interests, it can be desirable with solutions that make it possible to produce
      labels from a selection of different topical categories. We therefore introduce
      the concept of multi-focus cluster labeling to give users the possibility to get
      an overview of the contents through labels from multiple viewpoints. The concept
      for multi-focus cluster labeling has been established and has been demonstrated
      on three different document collections. We illustrate that multi-focus
      visualizations can give an overview of clusters along axes that general labels
      are not able to convey. The approach is generic and should be applicable to any
      biomedical (or other) domain with any selection of foci where appropriate focus
      vocabularies can be established. A user evaluation also indicates that such a
      multi-focus concept is useful. 

PMID- 25869417
TI  - Three quarters of doctors are confident in GMC regulation, researchers say.

PMID- 25869418
TI  - Energy efficient model based algorithm for control of building HVAC systems.
AB  - Energy efficient designs are receiving increasing attention in various fields of
      engineering. Heating ventilation and air conditioning (HVAC) control system
      designs involve improved energy usage with an acceptable relaxation in thermal
      comfort. In this paper, real time data from a building HVAC system provided by
      BuildingLAB is considered. A resistor-capacitor (RC) framework for representing
      thermal dynamics of the building is estimated using particle swarm optimization
      (PSO) algorithm. With objective costs as thermal comfort (deviation of room
      temperature from required temperature) and energy measure (Ecm) explicit MPC
      design for this building model is executed based on its state space
      representation of the supply water temperature (input)/room temperature (output)
      dynamics. The controllers are subjected to servo tracking and external
      disturbance (ambient temperature) is provided from the real time data during
      closed loop control. The control strategies are ported on a PIC32mx series
      microcontroller platform. The building model is implemented in MATLAB and
      hardware in loop (HIL) testing of the strategies is executed over a USB port.
      Results indicate that compared to traditional proportional integral (PI)
      controllers, the explicit MPC's improve both energy efficiency and thermal
      comfort significantly. 

PMID- 25869419
TI  - Influence of bentonite in polymer membranes for effective treatment of car wash
      effluent to protect the ecosystem.
AB  - In this study, modified polyethersulfone (PES) and cellulose acetate (CA)
      membranes were used in the treatment of car wash effluent using ultrafiltration.
      Hydrophilic sulfonated poly ether ether ketone (SPEEK) and bentonite as nanoclay
      were used as additives for the PES and CA membrane modification. Performances of
      modified membranes were compared with commercial PES membrane with 10kDa
      molecular weight cut off (MWCO). The influencing parameters like stirrer speed
      (250-750rpm) and transmembrane pressure (100-600kPa) (TMP) were varied and their
      effects were studied as a function of flux. In the treatment of car wash
      effluent, a higher permeate flux of 52.3L/m(2)h was obtained for modified CA
      membrane at TMP of 400kPa and stirrer speed of 750rpm. In comparison with
      modified PES membrane and commercial PES membrane, modified CA membranes showed
      better performance in terms of flux and flux recovery ratio. The highest COD
      removal (60%) was obtained for modified CA membrane and a lowest COD removal
      (47%) was observed for commercial PES membrane. The modified membranes were
      better at removing COD, turbidity and maintained more stable flux than commercial
      PES membrane, suggesting they will provide better economic performance in car
      wash effluent reclamation. 

PMID- 25869421
TI  - Immunomodulatory effects of umbilical cord-derived mesenchymal stem cells.
AB  - Umbilical cord blood (UCB) is of great interest as a source of stem cells for use
      in cellular therapies. The immunomodulatory effect of mesenchymal stem cells
      (MSCs) originating from bone marrow, adipose tissue and amniotic membrane has
      previously been reported. In this study, MSCs were isolated from UCB with the aim
      of evaluating their immunomodulatory effects on proliferation of PB lymphocytes
      by two different techniques; namely, 5-bromo-2-deoxyuridine ELISA and a carboxy
      fluorescein diacetate succinimidyl ester flow cytometric technique. MSCs were
      isolated from UCB, propagated until Passage four, and then characterized for cell
      surface markers by flow cytometry and ability to differentiate towards osteocytes
      and adipocytes. Immunosuppressive effects on PB lymphocytes were examined by co
      culturing mitomycin C-treated UCB MSCs with mitogen-stimulated lymphocytes for 72
      hr. Thereafter, proliferation of lymphocytes was detected by CFSE flow cytometry
      and colorimetric ELISA. The titers of cytokines in cell culture supernatant were
      also assayed to clarify possible mechanisms of immunomodulation. UCB MSCs
      suppressed mitogen-stimulated lymphocyte proliferation, which occurs via both
      cell-cell contact and cytokine secretion. Titers of transforming growth factor
      beta and IL 10 increased, whereas that of IFN-gamma decreased in the supernatants
      of co-cultures. Thus, UCB MSCs suppress the proliferation of mitogen-stimulated
      lymphocytes. However further in vivo studies are required to fully evaluate the
      immunomodulatory effects of UCB MSCs. 

PMID- 25869422
TI  - Comparison of hip and knee strength in males with and without patellofemoral
      pain.
AB  - OBJECTIVES: The primary purpose of this study was to compare hip strength in
      males with and without patellofemoral pain (PFP). The secondary purpose was to
      compare knee strength in males with and without PFP. DESIGN: Secondary analysis
      of cross-sectional data for males with and without PFP from a larger randomized
      controlled trial examining hip and core versus knee-muscle strengthening for the
      treatment of PFP. SETTING: Laboratory setting. PARTICIPANTS: Sixty-six males with
      PFP and 36 controls. MAIN OUTCOME MEASURES: Peak isometric force for the hip
      abductors, external rotators, internal rotators, extensors, and knee extensors
      expressed as a percentage of body mass (%BM). RESULTS: No differences existed
      with respect to any of the hip strength measures (P > .05). Males with PFP
      demonstrated almost 17% less knee extensor strength than controls (mean
      difference = 7.3 %BM; 95% confidence interval, 1.3-13.4 %BM; t = 2.41; P = .02).
      CONCLUSIONS: Unlike females, males with PFP did not demonstrate hip muscle
      weakness. However, differences did exist with knee extensor strength. These data
      provide preliminary evidence for the potential need for sex-specific
      interventions for individuals with PFP.

PMID- 25869420
TI  - Helminths and the microbiota: parts of the hygiene hypothesis.
AB  - In modern societies, diseases that are driven by dysregulated immune responses
      are increasing at an alarming pace, such as inflammatory bowel diseases and
      diabetes. There is an urgent need to understand these epidemiological trends,
      which are likely to be driven by the changing environment of the last few
      decades. There are complex interactions between human genetic factors and this
      changing environment that is leading to the increasing prevalence of metabolic
      and inflammatory diseases. Alterations to human gut bacterial communities (the
      microbiota) and lowered prevalence of helminth infections are potential
      environmental factors contributing to immune dysregulation. Helminths have co
      evolved with the gut microbiota and their mammalian hosts. This three-way
      interaction is beginning to be characterized, and the knowledge gained may enable
      the design of new therapeutic strategies to treat metabolic and inflammatory
      diseases. However, these complex interactions need to be carefully investigated
      in the context of host genetic backgrounds to identify optimal treatment
      strategies. The complex nature of these interactions raises the possibility that
      only with highly personalized treatment, with knowledge of individual genetic and
      microbiota communities, will therapeutic interventions be successful for a
      majority of the individuals suffering from these complex diseases of immune
      dysregulation. 

PMID- 25869423
TI  - Longer reaction time of the fibularis longus muscle and reduced postural control
      in basketball players with functional ankle instability: A pilot study.
AB  - BACKGROUND: Motor control evaluation in subjects with functional ankle
      instability is questionable when both ankles of the same subject are compared
      (affected vs non-affected). OBJECTIVE: To compare the postural control and
      reaction time of ankle muscles among: basketball players with FAI (instability
      group), basketball players without FAI (non-instability group) and healthy non
      basketball-playing participants (control group). DESIGN: Case-control study.
      SETTING: Laboratory. PARTICIPANTS: Instability (n = 10), non-instability (n =
      10), and control groups (n = 11). MAIN OUTCOME MEASURES: Centre of pressure
      variables (area, velocity and sway) were measured with a force platform. Reaction
      time of ankle muscles was measured via electromyography. RESULTS: A one-way ANOVA
      demonstrated that there were significant differences between the instability and
      non-instability groups in the fibularis longus (p < 0.001), fibularis brevis (p =
      0.031) and tibialis anterior (p = 0.049) muscles. Repeated-measures ANOVA and
      post hoc analysis determined significant differences for the area between the
      instability and non-instability groups (p = 0.001). CONCLUSION: Basketball
      players with FAI have reduced postural control and longer reaction time of the
      fibularis and tibialis anterior muscles.

PMID- 25869424
TI  - Impact of the FIFA 11+ on the structure of select muscles in adolescent female
      soccer players.
AB  - OBJECTIVES: To determine the impact of an injury prevention program (FIFA11+) on
      the structure of select trunk and leg muscles in adolescent female soccer
      players. DESIGN: Exploratory analysis. SETTING: University Sport Medicine Centre.
      PARTICIPANTS: 23 female soccer players (aged 14-16) recruited from a FIFA11 +
      implementation trial grouped by high and low 11 + exposure. MAIN OUTCOMES: Pre
      and post-season sonographic measures of the rectus abdominis, external and
      internal oblique, transversus abdominis, inter-recti distance (IRD), lumbar
      multifidus, gluteus medius and minimus, and vastus medialis. Mean (95% confidence
      intervals; CI) were calculated for pre, post and pre-post season change of all
      parameters and univariate analyses used to compare groups (alpha = 0.001).
      RESULTS: Both low (mean = 149 +/- 9 exercises/year) and high (mean = 314 +/- 15
      exercises/year) 11 + exposure groups demonstrated significant post-season
      decreases in IRD at rest (p < 0.001) and during a leg lift (p < 0.001). No other
      between or within group differences existed. CONCLUSIONS: Levels of FIFA11 +
      exposure were not associated with differential changes in the morphology of
      investigated muscles. As the IRD of participants in both exposure groups
      decreased it is possible that the protective mechanism of the FIFA11 + may be
      associated with alterations in neuromuscular control that result in abdominal
      wall adaptations.

PMID- 25869425
TI  - Relationship between static and dynamic balance abilities in Italian professional
      and youth league soccer players.
AB  - OBJECTIVES: To assess the existence of correlations between static and dynamic
      balance abilities in young and professional elite soccer players. DESIGN: Cross
      sectional. PARTICIPANTS: Fifty-one elite players who regularly compete at
      national level divided into two groups: Professional (age 18-34, n = 20) and
      Under 15-17 (age 14-16, n = 31). MAIN OUTCOME MEASURES: Dynamic balance was
      assessed for the case of a single-leg landing task by means of vertical time to
      stabilization (TTS) and postural sway calculated on the basis of center-of
      pressure (COP) trajectories (sway area, COP displacements in antero-posterior and
      medio-lateral direction, COP path length). The same parameters were also measured
      for a 20 s one-legged stance to assess static balance abilities. RESULTS: No
      significant correlations were found between static and dynamic balance parameters
      except for TTS and COP displacements in the antero-posterior direction (r = 0.29,
      p = 0.003). Professional players are characterized by lower TTS in comparison
      with youth leagues players (0.767 vs. 1.188 s for the dominant limb, p < 0.001)
      and exhibit reduced sway area (of 34-40%, p < 0.05) for both conditions tested.
      CONCLUSION: The assessment of balance in soccer players should be performed with
      both dynamic and static tests, considering that the postural control performances
      in the two cases are not related.

PMID- 25869426
TI  - Role of estrogen receptor-alpha on food demand elasticity.
AB  - Estrogens have been shown to have an inhibitory effect on food intake under free
      feeding conditions, yet the effects of estrogens on food-maintained operant
      responding have been studied to a much lesser extent and, thus, are not well
      understood. Therefore, the purpose of the present experiment was to use a
      behavioral economics paradigm to assess differences in demand elasticity between
      mice with knockout of the estrogen receptor subtype alpha, knockout of subtype
      beta, and their wild type controls. The mice responded in a closed economy, and
      the price of food was increased by increasing the fixed-ratio response
      requirement every four sessions. Overall, we found that mice with the knockout of
      receptor subtype alpha had the most elastic demand functions. Therefore, under
      these conditions, estrogens increased food seeking via activation of the receptor
      subtype alpha. The results were inconsistent with those reported by previous
      studies that employed free-feeding conditions. 

PMID- 25869427
TI  - Dynamics and distribution of bacterial and archaeal communities in oil
      contaminated temperate coastal mudflat mesocosms.
AB  - Mudflats are ecologically important habitats that are susceptible to oil
      pollution, but intervention is difficult in these fine-grained sediments, and so
      clean-up usually relies on natural attenuation. Therefore, we investigated the
      impact of crude oil on the bacterial, diatom and archaeal communities within the
      upper parts of the diatom-dominated sediment and the biofilm that detached from
      the surface at high tide. Biodegradation of petroleum hydrocarbons was rapid,
      with a 50 % decrease in concentration in the 0-2-mm section of sediment by 3
      days, indicating the presence of a primed hydrocarbon-degrading community. The
      biggest oil-induced change was in the biofilm that detached from the sediment,
      with increased relative abundance of several types of diatom and of the
      obligately hydrocarbonoclastic Oleibacter sp., which constituted 5 % of the
      pyrosequences in the oiled floating biofilm on day 3 compared to 0.6 % in the non
      oiled biofilm. Differences in bacterial community composition between oiled and
      non-oiled samples from the 0-2-mm section of sediment were only significant at
      days 12 to 28, and the 2-4-mm-sediment bacterial communities were not
      significantly affected by oil. However, specific members of the Chromatiales were
      detected (1 % of sequences in the 2-4-mm section) only in the oiled sediment,
      supporting other work that implicates them in anaerobic hydrocarbon degradation.
      Unlike the Bacteria, the archaeal communities were not significantly affected by
      oil. In fact, changes in community composition over time, perhaps caused by
      decreased nutrient concentration and changes in grazing pressure, overshadowed
      the effect of oil for both Bacteria and Archaea. Many obligate
      hydrocarbonoclastic and generalist oil-degrading bacteria were isolated, and
      there was little correspondence between the isolates and the main taxa detected
      by pyrosequencing of sediment-extracted DNA, except for Alcanivorax,
      Thalassolituus, Cycloclasticus and Roseobacter spp., which were detected by both
      methods.

PMID- 25869428
TI  - Hexabromocyclododecane diastereoisomers in surface sediments from river drainage
      basins of Shanghai, China: occurrence, distribution, and mass inventory.
AB  - Concentrations of hexabromocyclododecanes (HBCDs) were determined in surface
      sediments of Shanghai, China. The concentrations of total HBCD diastereoisomers
      (SigmaHBCD) ranged from 0.01 to 13.70 ng g(-1) dry weight (dw) with a mean value
      of 3.41 ng g(-1) dw, which was up to several orders of magnitude lower than those
      reported for sediments from European countries. The SigmaHBCD concentrations in
      sediments from chemical/textile industrial or densely populated areas were
      generally higher than those from rural or less chemical/textile industrialized
      areas in Shanghai. A high proportion of alpha-HBCD was observed in sediment
      samples and was significantly higher than that of commercial HBCD products. This
      might be due to thermal isomerization from gamma-HBCD to alpha-HBCD and slower
      degradation rate of alpha-HBCD compared to gamma-HBCD in anaerobic conditions.
      The mass inventory of SigmaHBCD in surface sediments of Shanghai was estimated at
      164.4 kg, representing a significant source of HBCDs to the Shanghai environment.
      This indicates that further study on potential transfer of HBCDs from sediments
      to aquatic organisms and ecological risk assessments is required.

PMID- 25869430
TI  - Quantitative and qualitative assessment of the impact of climate change on a
      combined sewer overflow and its receiving water body.
AB  - Projections from the Canadian Regional Climate Model (CRCM) for the southern part
      of the province of Quebec, Canada, suggest an increase in extreme precipitation
      events for the 2050 horizon (2041-2070). The main goal of this study consisted in
      a quantitative and qualitative assessment of the impact of the 20 % increase in
      rainfall intensity that led, in the summer of 2013, to overflows in the "Rolland
      Therrien" combined sewer system in the city of Longueuil, Canada. The PCSWMM 2013
      model was used to assess the sensitivity of this overflow under current (2013)
      and future (2050) climate conditions. The simulated quantitative variables (peak
      flow, Q(CSO), and volume discharged, VD) served as the basis for deriving
      ecotoxicological risk indices and event fluxes (EFs) transported to the St.
      Lawrence (SL) River. Results highlighted 15 to 500% increases in VD and 13 to
      148% increases in Q(CSO) by 2050 (compared to 2013), based on eight rainfall
      events measured from May to October. These results show that (i) the
      relationships between precipitation and combined sewer overflow variables are not
      linear and (ii) the design criteria for current hydraulic infrastructure must be
      revised to account for the impact of climate change (CC) arising from changes in
      precipitation regimes. EFs discharged into the SL River will be 2.24 times larger
      in the future than they are now (2013) due to large VDs resulting from CC. This
      will, in turn, lead to excessive inputs of total suspended solids (TSSs) and
      tracers for numerous urban pollutants (organic matter and nutrients, metals) into
      the receiving water body. Ecotoxicological risk indices will increase by more
      than 100% by 2050 compared to 2013. Given that substantial VDs are at play, and
      although CC scenarios have many sources of uncertainty, strategies to adapt this
      drainage network to the effects of CC will have to be developed.

PMID- 25869429
TI  - Ruditapes philippinarum and Ruditapes decussatus under Hg environmental
      contamination.
AB  - The native species Ruditapes decussatus and the invasive species Ruditapes
      philippinarum have an important ecological role and socio-economic value, from
      the Atlantic and Mediterranean to the Indo-Pacific region. In the aquatic
      environment, they are subjected to the presence of different contaminants, such
      as mercury (Hg) and its methylated form, methylmercury (MeHg). However, few
      studies have assessed the impacts of Hg on bivalves under environmental
      conditions, and little is known on bivalve oxidative stress patterns due to Hg
      contamination. Therefore, this study aims to assess the Hg contamination in
      sediments as well as the concentration of Hg and MeHg in R. decussatus and R.
      philippinarum, and to identify the detoxification strategies of both species
      living in sympatry, in an aquatic system with historical Hg contamination. The
      risk to human health due to the consumption of clams was also evaluated. The
      results obtained demonstrated that total Hg concentration found in sediments from
      the most contaminated area was higher than the maximum levels established by
      Sediment Quality Guidelines. This study further revealed that the total Hg and
      MeHg accumulation in both species was strongly correlated with the total Hg
      contamination of the sediments. Nonetheless, the THg concentration in both
      species was lower than maximum permissible limits (MPLs) of THg defined by
      international organizations. R. decussatus and R. philippinarum showed an
      increase in lipid peroxidation levels along with the increase of THg accumulation
      by clams. Nevertheless, for both species, no clear trend was obtained regarding
      the activity of antioxidant (superoxide dismutase, catalase) and
      biotransformation (glutathione S-transferase) enzymes and metallothioneins with
      the increase of THg in clams. Overall, the present work demonstrated that both
      species can be used as sentinel species of contamination and that the consumption
      of these clams does not constitute a risk for human health. 

PMID- 25869431
TI  - Amplified solubilization effects of inherent dissolved organic matter releasing
      from less-humified sediment on phenanthrene sorption.
AB  - Soil/sediment organic matter (SOM) releasing with inherent dissolved organic
      matter (DOM) formed in solution was confirmed both in rhizosphere sediment (S)
      and uncultivated sediment (P) water systems, and correlations between SOM
      characteristics subject to sediment's humification degree and its releasing
      effects on phenanthrene sorption were emphasized. The sequential SOM releasing
      evidenced by fluorescence and (1)H-NMR profiles coupled with aqueous DOM
      solubilization was found to make sorption kinetics atypical and sorption capacity
      reduced, by comparing sorption results among sediments of different
      pretreatments. More importantly, the tested S was proved less humified with
      inherent DOM rich in microbial sources than P, and DOM affinity to phenanthrene
      was thus weakened (K doc values of 2.02-3.63 * 10(4) L kg(-1)), while the
      inhibitive effects of SOM releasing on sorption were strengthened, ascribing to
      the enlarged alterations of sediment characters, and particularly the amplified
      solubilization effects resulted from the larger proportion of soluble SOM and
      lower critical micelle concentration (5.66 mg L(-1)) of DOM. Moreover, relative
      contribution of DOM solubilization to the releasing effects enhanced from 0.67
      for P to 0.78 for S relative to alterations of sediment characters. Consequently,
      mobility and exposure risk of polycyclic aromatic hydrocarbons would be enhanced
      in a plant-soil/sediment-water system.

PMID- 25869432
TI  - Alkylphenol ethoxylates and brominated flame retardants in water, fish (carp) and
      sediment samples from the Vaal River, South Africa.
AB  - Alkylphenol ethoxylates (APEs) and brominated flame retardants (BFRs) are known
      to be bio-accumulative, persistent, and endocrine disruptors and can cause
      adverse health effects in animals and humans. In this study, environmental
      samples were collected from sites along the Vaal River, South Africa in order to
      determine the concentrations of APEs and BFRs in water, sediment, and fish
      samples. The highest concentrations of these pollutants were observed from
      discharge of the Rietspruit WWTW. Measurable levels of both APEs and BFRs were
      observed with APEs exhibiting higher concentrations than BFRs in all the
      matrices. The concentrations observed for APEs and BFRs were as follows: 1.00
      3.85 MUg/L APEs, 0.09-0.26 MUg/L PBDEs, ND- 0.14 PBBs and 0.51-1.77 MUg/L HBCD
      for water samples; 47-63 ng/g lipid APEs, 3.24-12.4 ng/g lipid PBB, 4.63-33 ng/g
      lipid PBDEs and 10-13 ng/g lipid HBCD for fish; and 40-184 ng/g (wet weight (ww))
      APEs, 2.93-5.9 ng/g (ww) PBB, 10-24 ng/g (ww) PBDEs, and 15-52 ng/g (ww) HBCD for
      sediment samples. The concentrations of APEs and BFRs in water samples were found
      to be in the range with the results reported in the literature while the
      concentration in fish and sediment were lower than the concentrations reported in
      other studies.

PMID- 25869433
TI  - Evaluation of the distribution of fecal indicator bacteria in a river system
      depending on different types of land use in the southern watershed of the Baltic
      Sea.
AB  - The aim of the study was to determine the effects of land use management on
      changes in the fecal contamination of water in the Lyna River, one of the main
      lowland watercourses in the southern watershed of the Baltic Sea (northern
      Poland). A total of 120 water samples were collected in different seasons of 2011
      and 2012 at 15 sites where the river intersected forest (FA), agricultural (AA),
      and urbanized (UA) areas. Fecal indicator bacteria (FIB), the counts of
      Enterobacteriaceae and Escherichia coli, total bacterial counts (TBCs), and
      domain Bacteria (EUB338) were determined by culture-dependent and culture
      independent methods. Temperature, pH, chemical oxygen demand, dissolved oxygen,
      total dissolved solids, ammonia nitrogen, nitrite nitrogen, nitrate nitrogen,
      orthophosphate, and total phosphorus were also determined. The lowest bacterial
      counts were noted in water samples collected in FA, and the highest in samples
      collected in UA. Statistically significant differences were determined between
      bacterial populations across the analyzed land use types and in different
      sampling seasons. Significant correlations were also observed between the
      populations of FIB and physicochemical parameters. The results indicate that land
      use type influenced FIB concentrations in river water. The combined use of
      conventional and molecular methods improves the accuracy of fecal contamination
      analyses in river ecosystems. 

PMID- 25869435
TI  - PAHs in leachates from thermal power plant wastes and ash-based construction
      materials.
AB  - The focus of the current study is to characterise the leaching behaviour of
      polycyclic aromatic hydrocarbons (PAHs) from oil shale ashes (OSAs) of pulverised
      firing (PF) and circulating fluidised-bed (CFB) boilers from Estonian Thermal
      Power Plant (Estonia) as well as from mortars and concrete based on OSAs. The
      target substances were 16 PAHs from the EPA priority pollutant list. OSA samples
      and OSA-based mortars were tested for leaching, according to European standard EN
      12457-2 (2002). European standard CEN/TC 15862(2012) for monolithic matter was
      used for OSA-based concrete. Water extracts were analysed by GC-MS for the
      concentration of PAHs. Naphthalene, acenaphthene, fluorene, phenanthrene,
      anthracene, fluoranthene and pyrene were detected. Still, the release of PAHs was
      below the threshold limit value for inert waste. The amount of the finest
      fraction (particle size <0.045 mm), the content of the Al-Si glass phase and the
      surface characteristics were the main factors, which could affect the
      accessibility of PAHs for leaching. The mobility of PAHs from OSA of CFB and PF
      boilers was 20.2 and 9.9%, respectively. Hardening of OSA-based materials did not
      lead to the immobilisation of soluble PAHs. Release of PAHs from the monolith
      samples did not exceed 0.5 MUg/m(2). In terms of leaching of PAHs, OSA is safe to
      be used for construction purposes.

PMID- 25869436
TI  - Genetic diversity of three classes of integrons in antibiotic-resistant bacteria
      isolated from Jiulong River in southern China.
AB  - We identified antibiotic-resistant bacterial isolates from the surface waters of
      Jiulong River basin in southern China and determined their extent of resistance,
      as well as the prevalence and characterization of three classes of integrons. A
      phylogenetic analysis of 16S ribosomal DNA (rDNA) sequences showed that 20 genera
      were sampled from a total of 191 strains and the most common genus was
      Acinetobacter. Antimicrobial susceptibility testing revealed that the 191
      isolates were all multiresistant and there were high levels of resistance to 19
      antimicrobials that were tested, particularly the beta-lactam, sulfonamide,
      amphenicol, macrolide, and rifamycin classes. Moreover, class 1 integrons were
      ubiquitous while only five out of 191 strains harbored class 2 integrons and no
      class 3 integrons were detected. The variable region of the class 1 integrons
      contained 30 different gene cassette arrays. Nine novel arrays were found in 65
      strains, and seven strains had empty integrons. Among these 30 arrays, there were
      34 different gene cassettes that included 25 resistance genes, six genes with
      unknown functions, two mutant transposase genes, and a new gene. The unique array
      dfrA1-sat2-aadA1 was detected in all five isolates carrying the class 2 integron.
      We found that antibiotic-resistant bacterial isolates from Jiulong River were
      diverse and antibiotic resistance genes associated with integrons were
      widespread. 

PMID- 25869434
TI  - The effect of oil spills on the bacterial diversity and catabolic function in
      coastal sediments: a case study on the Prestige oil spill.
AB  - The accident of the Prestige oil tanker in 2002 contaminated approximately 900 km
      of the coastline along the northern Spanish shore, as well as parts of Portugal
      and France coast, with a mixture of heavy crude oil consisting of polycyclic
      aromatic hydrocarbons, alkanes, asphaltenes and resins. The capacity of the
      autochthonous bacterial communities to respond to the oil spill was assessed
      indirectly by determining the hydrocarbon profiles of weathered oil samples
      collected along the shore, as well as through isotope ratios of seawater
      dissolved CO2, and directly by analyses of denaturing gradient gel
      electrophoresis fingerprints and 16S rRNA gene libraries. Overall, the results
      evidenced biodegradation of crude oil components mediated by natural bacterial
      communities, with a bias towards lighter and less substituted compounds. The
      changes observed in the Proteobacteria, the most abundant phylum in marine
      sediments, were related to the metabolic profiles of the sediment. The presence
      of crude oil in the supratidal and intertidal zones increased the abundance of
      Alpha- and Gammaproteobacteria, dominated by the groups Sphingomonadaceae,
      Rhodobacteraceae and Chromatiales, whilst Gamma- and Deltaproteobacteria were
      more relevant in subtidal zones. The phylum Actinobacteria, and particularly the
      genus Rhodococcus, was a key player in the microbial response to the spill,
      especially in the degradation of the alkane fraction. The addition of inorganic
      fertilizers enhanced total biodegradation rates, suggesting that, in these
      environments, nutrients were insufficient to support significant growth after the
      huge increase in carbon sources, as evidenced in other spills. The presence of
      bacterial communities able to respond to a massive oil input in this area was
      consistent with the important history of pollution of the region by crude oil.

PMID- 25869437
TI  - The influence of meteorological conditions and anthropogenic activities on the
      seasonal fluctuations of BTEX in the urban air of the Hanseatic city of Gdansk,
      Poland.
AB  - The results of studies conducted in Gdansk in the period from January to December
      2013 and focused on the determination of BTEX in the atmospheric air are
      presented. At the stage of the isolation and/or enrichment of analytes from the
      gaseous medium, a passive sampling technique-Radiello(r) diffusive passive
      samplers, was applied. The time-weighted average annual concentration of benzene,
      toluene, ethylbenzene, and total xylenes determined in the monitored area was as
      follows: 0.66 +/- 0.32, 1.63 +/- 0.94, 0.67 +/- 0.61, and 2.9 +/- 2.7 MUg/m(3).
      As a result of the research, the potential emission sources of BTEX, which
      activity has a significant impact on the concentration of these compounds in the
      atmosphere in the Gdansk area, were identified. A comparison of the accuracy and
      precision of the results of benzene concentrations in the atmosphere obtained by
      the BTEX automatic analyzer and passive techniques was performed. Moreover, a
      significant influence of meteorological conditions, such as air temperature,
      intensity of solar radiation, velocity and direction of wind, humidity, and
      rainfall on the benzene content in ambient air was shown. Additionally, in order
      to determine the conditions in the area covered by the monitoring, information
      about atmospheric stability and the height of the mixing layer was presented.

PMID- 25869439
TI  - Hierarchical nonlinear dynamics of human attention.
AB  - Attention is the process of focusing mental resources on a specific
      cognitive/behavioral task. Such brain dynamics involves different partially
      overlapping brain functional networks whose interconnections change in time
      according to the performance stage, and can be stimulus-driven or induced by an
      intrinsically generated goal. The corresponding activity can be described by
      different families of spatiotemporal discrete patterns or sequential dynamic
      modes. Since mental resources are finite, attention modalities compete with each
      other at all levels of the hierarchy, from perception to decision making and
      behavior. Cognitive activity is a dynamical process and attention possesses some
      universal dynamical characteristics. Thus, it is time to apply nonlinear
      dynamical theory for the description and prediction of hierarchical attentional
      tasks. Such theory has to include the analyses of attentional control stability,
      the time cost of attention switching, the finite capacity of informational
      resources in the brain, and the normal and pathological bifurcations of attention
      sequential dynamics. In this paper we have integrated today's knowledge, models
      and results in these directions. 

PMID- 25869438
TI  - Effect of linear alkylbenzene mixtures and sanitary sewage in biochemical and
      molecular responses in pacific oyster Crassostrea gigas.
AB  - Urban effluents are rich in nutrients, organic matter, pharmaceuticals and
      personal care products (PPCPs), pesticides, hydrocarbons, surfactants, and
      others. Previous studies have shown that oysters Crassostrea gigas accumulate
      significant levels of linear alkylbenzenes (LABs) in sanitary sewage contaminated
      sites, but there is little information about its toxicological effects in marine
      bivalves. The aim of this study was to analyze the transcription of genes in two
      tissues of C. gigas exposed for 12, 24, and 36 h to LABs or sanitary sewage.
      Likewise, the activity of antioxidant and biotransformation enzymes was measured
      in oysters exposed for 36 h in all groups. Oysters exposed to LABs and oysters
      exposed to sanitary sewage showed different patterns of transcriptional
      responses. LAB-exposed oysters showed lower level of biological responses than
      the oysters exposed to sanitary sewage. Despite the ability of the oyster C.
      gigas to accumulate LABs (28-fold), the data indicate that these contaminants are
      not the cause for the transcriptional responses observed in oysters exposed to
      sanitary sewage. Possibly, the biological changes observed in the sanitary sewage
      exposed oysters are associated with the presence of other contaminants, which
      might have caused synergistic, additive, or antagonistic effects. The results
      show that FABP-like and GST-omega-like messenger RNAs (mRNAs) have a rapid
      response in tissues of oyster C. gigas exposed to sanitary sewage, suggesting a
      possible protective response and a role in maintaining homeostasis of these
      organisms.

PMID- 25869440
TI  - An ESIPT-based fluorescent probe for sensitive detection of hydrazine in aqueous
      solution.
AB  - A fluorescent probe for sensitive detection of hydrazine based on an ESIPT
      mechanism and a substitution-cyclization-elimination cascade was developed. After
      the addition of hydrazine, an approximately 50-fold enhancement in fluorescence
      intensity at 465 nm was observed and the subsequent decrease at 375 nm was
      observed in 10 min with a detection limit of 0.147 MUM. We also detected
      hydrazine in HeLa cells successfully. 

PMID- 25869443
TI  - [Assessment of patients' knowledge of first-trimester combined Down syndrome
      screening at the time of their first trimester ultrasonographic evaluation:
      Results of a prospective study about 201 women].
AB  - OBJECTIVE: Assess pregnant women's knowledge on first-trimester combined Down
      syndrome screening, at the time of their first trimester ultrasound scan.
      MATERIALS AND METHODS: A questionnaire was submitted to the patients coming for
      their 12-week pregnancy ultrasonographic evaluation in a University Hospital
      prenatal clinic between May 2012 and May 2013. Correct and incorrect statements
      on Down syndrome screening were proposed to the mothers who were asked to rate
      them. Each patient was questioned on her prior exposition to Down syndrome
      screening, the category of medical of professional she previously consulted, and
      the information she received. Patients' knowledge was evaluated according to
      these criteria. RESULTS: Two hundred and one patients were included in this
      study. The average correct answer rating was 4.6 (out of 8 questions). The
      average incorrect answer rating was 2.4 (out of 6 questions). No difference was
      found between the different social and demographic groups, nor according to the
      category of professional consulted before the first ultrasound scan. Higher
      correct answer ratings were observed when the patient had already been submitted
      to a Down syndrome screening (P=0.039), when they had previously received
      explanations about the screening (P=0.003); and when they stated that they had
      been sufficiently informed (P=0.042). CONCLUSION: These results show that
      patients' knowledge on Down syndrome screening is inadequate and depends on their
      experience of previous screening and information. It is deemed necessary to
      improve information especially to young women who are pregnant for the first
      time.

PMID- 25869444
TI  - [Vitrification: Principles and results].
AB  - Sperm and embryos cryopreservation is a commonly applied technique for several
      years. Recently authorized in France, vitrification tends to replace gradually
      the conventional technique of slow freezing, so upsetting the practices in the
      management of patients. It allows from now on the cryopreservation of oocytes and
      opens new perspectives in egg donation either still in fertility preservation.
      This review thus attempted to examine the contribution of vitrification in the
      freezing of oocytes and human embryos at various stages of development. If
      obviously vitrification appears as the current method of choice for the
      cryopreservation of oocytes as well as blastocysts, the results are less cut as
      regards embryos to early stages. No increase in adverse obstetric and perinatal
      outcomes in children conceived from vitrified oocytes or embryos is noted in the
      literature.

PMID- 25869445
TI  - [Evaluation of practices of excisional therapies for CIN: An audit of surgery
      rooms from Marseilles' area].
AB  - OBJECTIVE: To evaluate what is the proportion of surgery rooms from Marseilles'
      area that do perform excisional therapies for CIN without any use of colposcopic
      guidance. MATERIALS AND METHODS: From November 2012 to January 2013, a survey was
      conducted among all surgery rooms from Marseilles' area practicing excisional
      therapies for CIN. In addition, answers from gynecologists from Marseilles' area
      who participated to a national survey that evaluated practices of excisional
      therapies in France were specifically analyzed. RESULTS: Among the 55 surgery
      rooms from Marseilles' area practicing excisional therapies, 52 (94.1%)
      participated to the current survey. A colposcope was available in only 19 (36.5%)
      surgery rooms and was systematically used for the guidance of excisional
      therapies in only 4 (21%) of these surgery rooms. Finally, 36 (69.2%) surgery
      rooms answered performing excisional therapies without any use of colposcopic
      guidance. Colposcopy was occasionally and systematically used in 12 (23.1%) and 4
      (7.7%) surgery rooms, respectively. Among the 116 gynecologists from Marseilles'
      area who answered to the national survey, 88 (75.9%) answered not using
      colposcopy when performing excision for CIN. Only 6% answered performing excision
      systematically under direct colposcopic vision and 18.1% occasionally.
      CONCLUSION: No colposcopic guidance is used when performing excision for CIN in
      the majority of surgery rooms from Marseilles' area.

PMID- 25869447
TI  - An automated fabrication strategy to create patterned tubular architectures at
      cell and tissue scales.
AB  - The use of materials to impose tissue-like architecture at cell resolution will
      be important if engineered functional replacements for damaged cardiovascular,
      pulmonary, renal or digestive tissues are to be authentically engineered. Here,
      we demonstrate a coordinated system for the fabrication and subsequent culture of
      tubular tissues composed of multiple layers, cell-types and materials with
      physiological dimensions and defined architectures at cell resolution. We
      developed an automated tube fabricator that rolls 2D-matrices into 3D-tubular
      constructs directly from cells, hydrogels and scaffold biomaterials. Coordinated
      use of surface modification strategies allows 2D cell sheets and cell/biomaterial
      composites (i.e. hydrogels or electrospun scaffolds) to be fabricated which may
      be transferred into a perfusion bioreactor in a rapid and standardized procedure.
      To exemplify our strategy we fabricated structures resembling human mammary
      artery and gut; these can be imaged in situ and real-time electrical resistance
      measurements performed of the vessel walls, allowing non-invasive assessment of
      viability and functionality. Our system allows patterning at cellular resolution
      with variable tissue thickness, length, luminal diameter, and constituent
      biomaterial. This inherent flexibility will allow the recapitulation of the
      complex hierarchical biological architectures and generate functionality found
      natively in vivo.

PMID- 25869448
TI  - Clinical relevance of the number of interleukin-17-producing CD 8+ T cells in
      patients with gastric cancer.
AB  - PURPOSE: There is accumulating evidence that inflammation is linked to cancer
      development and progression. Interleukin-17 (IL-17), an inflammatory cytokine, is
      produced by CD 8+ T cells (Tc17 cells); however, the specific role of Tc17 cells
      in tumor immunity against gastric cancer remains unclear. METHODS: The prevalence
      of Tc17 cells in both peripheral blood mononuclear cells and gastric tissue was
      evaluated by multicolor flow cytometry and the concentration of IL-17 in sera was
      quantitated by an enzyme-linked immunosorbent assay. RESULTS: Circulating Tc17
      cells were significantly more numerous in gastric cancer patients than in
      controls, and significantly more numerous before surgery than after surgery. IL
      17 concentrations in gastric cancer patients and healthy controls were 0.51 +/-
      0.54 and 0.084 +/- 0.084 pg/mL, respectively, with this difference being
      significant. The percentage of Tc17 cells was significantly related to serum IL
      17 concentration. Tc17 cells were significantly more numerous than peripheral
      blood mononuclear cells in gastric cancer tissue. Furthermore, Tc17 cells were
      more numerous in cancerous gastric tissue than in normal gastric tissue.
      CONCLUSIONS: Tc17 cells may be the main source of IL-17 in gastric cancer
      patients and thus involved in the progression of gastric cancer.

PMID- 25869449
TI  - The Impact of Nursing Students' Cultural Diversity on the Intention and Attitudes
      Toward the Use of Information Technology.
AB  - This research highlights the evidences that: The greater the threat, the lower
      the attitude toward information technology is, and the greater the sense of
      challenge, the greater self-efficacy is. Innovativeness was found to be a
      behavioral intention predictor in two groups, secular Jews and Arabs. This study
      provides nurses and nurse educators with some valuable insights about how
      culture, religion, and education may influence nursing students' attitudes toward
      information technology. 

PMID- 25869446
TI  - Protocadherins branch out: Multiple roles in dendrite development.
AB  - The proper formation of dendritic arbors is a critical step in neural circuit
      formation, and as such defects in arborization are associated with a variety of
      neurodevelopmental disorders. Among the best gene candidates are those encoding
      cell adhesion molecules, including members of the diverse cadherin superfamily
      characterized by distinctive, repeated adhesive domains in their extracellular
      regions. Protocadherins (Pcdhs) make up the largest group within this
      superfamily, encompassing over 80 genes, including the ~60 genes of the alpha-,
      beta-, and gamma-Pcdh gene clusters and the non-clustered delta-Pcdh genes. An
      additional group includes the atypical cadherin genes encoding the giant Fat and
      Dachsous proteins and the 7-transmembrane cadherins. In this review we highlight
      the many roles that Pcdhs and atypical cadherins have been demonstrated to play
      in dendritogenesis, dendrite arborization, and dendritic spine regulation.
      Together, the published studies we discuss implicate these members of the
      cadherin superfamily as key regulators of dendrite development and function, and
      as potential therapeutic targets for future interventions in neurodevelopmental
      disorders. 

PMID- 25869450
TI  - Mini-tablets versus pellets as promising multiparticulate modified release
      delivery systems for highly soluble drugs.
AB  - Whether mini-tablets (tablets, diameters <=6mm) belong to single- or multiple
      unit dosage forms is still questionable. Accordingly, Pharmacopoeial evaluation
      procedures for mini-tablets are lacking. In this study, the aforementioned points
      were discussed. Moreover, their potential for oral controlled delivery was
      assessed. The antidepressant venlafaxine hydrochloride (Vx), a highly soluble
      drug undergoing first pass effect, low bioavailability and short half-life was
      selected as a challenging payload. In an attempt to weigh up mini-tablets versus
      pellets as multiparticulate carriers, Vx-loaded mini-tablets were compared to
      formulated pellets of the same composition and the innovator Effexor((r))XR
      pellets. Formulations were prepared using various polymer hydrogels in the core
      and ethyl cellulose film coating with increasing thickness. Mini-tablets
      (diameter 2mm) showed extended Vx release (<60%, 8h). Indeed, release profiles
      comparable to Effexor((r))XR pellets were obtained. Remarkably higher coating
      thickness was required for pellets to provide equivalent retardation. Ethyl
      cellulose in the core ensured faster release due to polymer migration to the
      surface and pore formation in the coat. mini-tablets showed higher stability to
      pellets upon storage. Industrially speaking, mini-tablets proved to be superior
      to pellets in terms of manufacturing, product quality and economical aspects.
      Results point out the urgent need for standardized evaluation procedures for mini
      tablets. 

PMID- 25869451
TI  - Twin screw wet granulation: Binder delivery.
AB  - The effects of three ways of binder delivery into the twin screw granulator (TSG)
      on the residence time, torque, properties of granules (size, shape, strength) and
      binder distribution were studied. The binder distribution was visualised through
      the transparent barrel using high speed imaging as well as quantified using
      offline technique. Furthermore, the effect of binder delivery and the change of
      screw configuration (conveying elements only and conveying elements with kneading
      elements) on the surface velocity of granules across the screw channel were
      investigated using particle image velocimetry (PIV). The binder was delivered in
      three ways; all solid binder incorporated with powder mixture, 50% of solid
      binder mixed with powder mixture and 50% mixed with water, all the solid binder
      dissolved in water. Incorporation of all solid binder with powder mixture
      resulted in the relatively longer residence time and higher torque, narrower
      granule size distribution, more spherical granules, weaker big-sized granules,
      stronger small-sized granules and better binder distribution compared to that in
      other two ways. The surface velocity of granules showed variation from one screw
      to another as a result of uneven liquid distribution as well as shown a reduction
      while introducing the kneading elements into the screw configuration. 

PMID- 25869441
TI  - Therapeutic targeting of replicative immortality.
AB  - One of the hallmarks of malignant cell populations is the ability to undergo
      continuous proliferation. This property allows clonal lineages to acquire
      sequential aberrations that can fuel increasingly autonomous growth,
      invasiveness, and therapeutic resistance. Innate cellular mechanisms have evolved
      to regulate replicative potential as a hedge against malignant progression. When
      activated in the absence of normal terminal differentiation cues, these
      mechanisms can result in a state of persistent cytostasis. This state, termed
      "senescence," can be triggered by intrinsic cellular processes such as telomere
      dysfunction and oncogene expression, and by exogenous factors such as DNA
      damaging agents or oxidative environments. Despite differences in upstream
      signaling, senescence often involves convergent interdependent activation of
      tumor suppressors p53 and p16/pRB, but can be induced, albeit with reduced
      sensitivity, when these suppressors are compromised. Doses of conventional
      genotoxic drugs required to achieve cancer cell senescence are often much lower
      than doses required to achieve outright cell death. Additional therapies, such as
      those targeting cyclin dependent kinases or components of the PI3K signaling
      pathway, may induce senescence specifically in cancer cells by circumventing
      defects in tumor suppressor pathways or exploiting cancer cells' heightened
      requirements for telomerase. Such treatments sufficient to induce cancer cell
      senescence could provide increased patient survival with fewer and less severe
      side effects than conventional cytotoxic regimens. This positive aspect is
      countered by important caveats regarding senescence reversibility, genomic
      instability, and paracrine effects that may increase heterogeneity and adaptive
      resistance of surviving cancer cells. Nevertheless, agents that effectively
      disrupt replicative immortality will likely be valuable components of new
      combinatorial approaches to cancer therapy. 

PMID- 25869453
TI  - Understanding the patient journey to the Emergency Department - A South
      Australian study.
AB  - BACKGROUND: To determine patients' points of contact prior to or decision making
      processes before presenting to an Emergency Department for treatment. To obtain
      data that may inform future exploration of targeted Emergency Department
      avoidance strategies. METHOD: All patients presenting to two metropolitan
      Emergency Departments over a 24h period were surveyed. Where information was
      unattainable, it was sought from computerised Patient Administration Systems used
      by each Emergency Department. A descriptive analysis of the results was
      undertaken. RESULTS: Three hundred and thirty two patients presented over the 48
      h survey period. Results showed that 200 (60.2%) were self-referred, 65 patients
      (19.6%) contacted their general practitioner, 22 (6.6%) were transferred from
      other hospitals and 3 patients (0.9%) contacted the National Healthdirect
      Australia triage hotline prior to presenting to the Emergency Department.
      CONCLUSION: The study showed 39.8% had sought advice from other health care
      professionals prior to presenting to the Emergency Department and that 60.2% of
      patients were self-referred. This study has not revealed any new pathways that
      warrant targeting for Emergency Department avoidance strategies. The focus still
      needs to target primary care referrals, ambulance service transports and smaller
      hospital transfers.

PMID- 25869452
TI  - Transcutaneous delivery of leflunomide nanoemulgel: Mechanistic investigation
      into physicomechanical characteristics, in vitro anti-psoriatic and anti-melanoma
      activity.
AB  - The present study is a mechanistic validation of 'proof of concept' of effective
      topical delivery of leflunomide (LFD) nanoemulgel for localized efficient
      treatment of psoriatic lesions as well as melanoma affected skin regions.
      Hyperproliferation of keratinocytes in psoriasis and symbiotic relationship
      between keratinocytes and melanocytes, justifies the need of dual acting
      treatment. LFD is recently introduced significantly effective disease modifying
      anti-rheumatic drug and has been considered valuable for the treatment of
      psoriatic arthritis as well as melanoma. Current available treatments for
      psoriasis and melanoma are inefficient due to systemic side effects, poor
      transcutaneous permeation and thus present a challenge for development of novel
      colloidal carriers. We newly reformulated LFD as a nanoemulgel based on self
      nanoemulsifying technique using Capryol 90, Cremophor EL, Transcutol HP as
      nanoemulsifying components and Pluronic F127 as a gelling agent. This
      thermodynamically stable nanoemuslsifying preconcentrate after gelation showed
      mean globule size, 123.7 nm and viscosity 9620 +/- 93 cp. Complete mechanical
      characterization was carried out using Texture Analyzer and hardness,
      adhesiveness and springiness index were found to be 523 gms, 431 gms and 1.02,
      respectively. Ex vivo permeation through rat abdominal skin revealed significant
      improvement in flux, apparent permeability coefficient, steady state diffusion
      coefficient and drug deposition in skin due to nanoemulsification of LFD. The in
      vitro cytoxicity of LFD nanoemulgel in human HaCaT, melanoma A375 and SK-MEL-2
      cell lines showed significantly enhanced therapeutic response. In gist, LFD
      nanoemulgel for trancutaneous delivery will reduce the overall dose and drug
      consumption, by effectively localizing at the applied target site and will
      ultimately minimize systemic side effects.

PMID- 25869442
TI  - Genomic instability in human cancer: Molecular insights and opportunities for
      therapeutic attack and prevention through diet and nutrition.
AB  - Genomic instability can initiate cancer, augment progression, and influence the
      overall prognosis of the affected patient. Genomic instability arises from many
      different pathways, such as telomere damage, centrosome amplification, epigenetic
      modifications, and DNA damage from endogenous and exogenous sources, and can be
      perpetuating, or limiting, through the induction of mutations or aneuploidy, both
      enabling and catastrophic. Many cancer treatments induce DNA damage to impair
      cell division on a global scale but it is accepted that personalized treatments,
      those that are tailored to the particular patient and type of cancer, must also
      be developed. In this review, we detail the mechanisms from which genomic
      instability arises and can lead to cancer, as well as treatments and measures
      that prevent genomic instability or take advantage of the cellular defects caused
      by genomic instability. In particular, we identify and discuss five priority
      targets against genomic instability: (1) prevention of DNA damage; (2)
      enhancement of DNA repair; (3) targeting deficient DNA repair; (4) impairing
      centrosome clustering; and, (5) inhibition of telomerase activity. Moreover, we
      highlight vitamin D and B, selenium, carotenoids, PARP inhibitors, resveratrol,
      and isothiocyanates as priority approaches against genomic instability. The
      prioritized target sites and approaches were cross validated to identify
      potential synergistic effects on a number of important areas of cancer biology. 

PMID- 25869454
TI  - A Novel Methodology for the Simulation of Athletic Tasks on Cadaveric Knee Joints
      with Respect to In Vivo Kinematics.
AB  - Six degree of freedom (6-DOF) robotic manipulators have simulated clinical tests
      and gait on cadaveric knees to examine knee biomechanics. However, these
      activities do not necessarily emulate the kinematics and kinetics that lead to
      anterior cruciate ligament (ACL) rupture. The purpose of this study was to
      determine the techniques needed to derive reproducible, in vitro simulations from
      in vivo skin-marker kinematics recorded during simulated athletic tasks. Input of
      raw, in vivo, skin-marker-derived motion capture kinematics consistently resulted
      in specimen failure. The protocol described in this study developed an in-depth
      methodology to adapt in vivo kinematic recordings into 6-DOF knee motion
      simulations for drop vertical jumps and sidestep cutting. Our simulation method
      repeatably produced kinetics consistent with vertical ground reaction patterns
      while preserving specimen integrity. Athletic task simulation represents an
      advancement that allows investigators to examine ACL-intact and graft
      biomechanics during motions that generate greater kinetics, and the athletic
      tasks are more representative of documented cases of ligament rupture.
      Establishment of baseline functional mechanics within the knee joint during
      athletic tasks will serve to advance the prevention, repair and rehabilitation of
      ACL injuries. 

PMID- 25869455
TI  - A Numerical Study of Water Loss Rate Distributions in MDCT-Based Human Airway
      Models.
AB  - Both three-dimensional (3D) and one-dimensional (1D) computational fluid dynamics
      methods are applied to study regional water loss in three multi-detector row
      computed-tomography-based human airway models at the minute ventilations of 6, 15
      and 30 L/min. The overall water losses predicted by both 3D and 1D models in the
      entire respiratory tract agree with available experimental measurements. However,
      3D and 1D models reveal different regional water loss rate distributions due to
      the 3D secondary flows formed at bifurcations. The secondary flows cause local
      skewed temperature and humidity distributions on inspiration acting to elevate
      the local water loss rate; and the secondary flow at the carina tends to
      distribute more cold air to the lower lobes. As a result, the 3D model predicts
      that the water loss rate first increases with increasing airway generation, and
      then decreases as the air approaches saturation, while the 1D model predicts a
      monotonic decrease of water loss rate with increasing airway generation.
      Moreover, the 3D (or 1D) model predicts relatively higher water loss rates in
      lower (or upper) lobes. The regional water loss rate can be related to the non
      dimensional wall shear stress (tau (*)) by the non-dimensional mass transfer
      coefficient (h 0 (*) ) as [Formula: see text]. 

PMID- 25869456
TI  - Atmospheric pressure nonthermal plasmas for bacterial biofilm prevention and
      eradication.
AB  - Biofilms are three-dimensional structures formed by surface-attached
      microorganisms and their extracellular products. Biofilms formed by pathogenic
      microorganisms play an important role in human diseases. Higher resistance to
      antimicrobial agents and changes in microbial physiology make treating biofilm
      infections very complex. Atmospheric pressure nonthermal plasmas (NTPs) are a
      novel and powerful tool for antimicrobial treatment. The microbicidal activity of
      NTPs has an unspecific character due to the synergetic actions of bioactive
      components of the plasma torch, including charged particles, reactive species,
      and UV radiation. This review focuses on specific traits of biofilms, their role
      in human diseases, and those effects of NTP that are helpful for treating biofilm
      infections. The authors discuss NTP-based strategies for biofilm control, such as
      surface modifications to prevent bacterial adhesion, killing bacteria in
      biofilms, and biofilm destruction with NTPs. The unspecific character of
      microbicidal activity, proven polymer modification and destruction abilities, low
      toxicity for human tissues and absence of long-living toxic compounds make NTPs a
      very promising tool for biofilm prevention and control. 

PMID- 25869457
TI  - Evaluation of cationic nanosystems with melatonin using an eye-related
      bioavailability prediction model.
AB  - In this study, two types of nanosystems, namely lecithin/chitosan nanoparticles
      and Pluronic(r) F127/chitosan micelles, have been prepared and evaluated for
      their potential for the ocular delivery of melatonin, which is known to exert an
      ocular hypotensive effect. The melatonin content, particle size, zeta potential
      and in vitro drug release properties were studied as a function of the presence
      of chitosan in the nanosystem. Lecithin/chitosan nanoparticles were evaluated in
      terms of the mucoadhesive properties by a newly established method based on HCE-T
      cells, also used in in vitro biocompatibility and permeability studies.
      Lecithin/chitosan nanoparticles were significantly larger than the corresponding
      F127/chitosan micelles (mean diameter of 241.8 vs. 20.7nm, respectively) and
      characterised by a higher surface charge (22.7 vs. 4.3mV, respectively). The HCE
      T cell viability assay did not show significant toxic effects of nanosystems
      investigated at the (relevant) chitosan concentration tested. The permeability
      study results confirmed the permeation enhancing effect of F127, which was
      hindered in the presence of chitosan. Lecithin/chitosan nanoparticles were
      characterised by prominent mucoadhesive properties and prolonged melatonin
      release, which was shown to control melatonin permeation across an in vitro
      corneal epithelial model. Such properties demonstrate the potential for
      nanoparticles to provide an extended pre-corneal residence time of melatonin,
      ensuring higher eye-related bioavailability and extended intraocular pressure
      reduction compared to melatonin in both aqueous and micelle solutions. 

PMID- 25869458
TI  - Semi-physiologic model validation and bioequivalence trials simulation to select
      the best analyte for acetylsalicylic acid.
AB  - The objective of this paper is to apply a previously developed semi-physiologic
      pharmacokinetic model implemented in NONMEM to simulate bioequivalence trials
      (BE) of acetyl salicylic acid (ASA) in order to validate the model performance
      against ASA human experimental data. ASA is a drug with first-pass hepatic and
      intestinal metabolism following Michaelis-Menten kinetics that leads to the
      formation of two main metabolites in two generations (first and second generation
      metabolites). The first aim was to adapt the semi-physiological model for ASA in
      NOMMEN using ASA pharmacokinetic parameters from literature, showing its
      sequential metabolism. The second aim was to validate this model by comparing the
      results obtained in NONMEM simulations with published experimental data at a dose
      of 1000 mg. The validated model was used to simulate bioequivalence trials at 3
      dose schemes (100, 1000 and 3000 mg) and with 6 test formulations with decreasing
      in vivo dissolution rate constants versus the reference formulation (kD 8-0.25 h
      (-1)). Finally, the third aim was to determine which analyte (parent drug, first
      generation or second generation metabolite) was more sensitive to changes in
      formulation performance. The validation results showed that the concentration
      time curves obtained with the simulations reproduced closely the published
      experimental data, confirming model performance. The parent drug (ASA) was the
      analyte that showed to be more sensitive to the decrease in pharmaceutical
      quality, with the highest decrease in Cmax and AUC ratio between test and
      reference formulations.

PMID- 25869459
TI  - Prostate cancer: MR-TRUS fusion biopsy--defining a new standard.

PMID- 25869460
TI  - Corrigendum: Management of locally advanced breast cancer--perspectives and
      future directions.

PMID- 25869461
TI  - Risk factors: After gestational chemotherapy, the kids are all right.

PMID- 25869462
TI  - The future of trials in surgical oncology.
AB  - Patients with cancer generally have better outcomes when treated as part of a
      clinical trial compared with patients not enrolled in a clinical trial.
      Unfortunately, surgical participation in, and leadership of such studies, is
      limited. This lack of clinical investigation is adversely affecting progress in
      cancer surgery research and, ultimately, hinders the treatment of patients. Some
      of the reasons for poor surgical participation in clinical research include:
      limitations on funding provision; inadequate training of junior surgeons in
      clinical trials methodology; and inadequate support of surgical faculty members
      as clinical investigators. Despite these shortcomings, numerous successful
      surgical studies have helped to change concepts, and improve patient care in
      certain clinical areas. Finally, a number of possible solutions are proposed,
      which might improve surgical involvement in clinical trials and result in more,
      and better-designed and executed clinical trials in this important area of
      research. 

PMID- 25869463
TI  - Haematological cancer: AETHERA--brentuximab wings its way as new standard of care
      in HL.

PMID- 25869464
TI  - Best reviewers award for 2014.

PMID- 25869465
TI  - MMP-9 in atrial remodeling in patients with atrial fibrillation.
AB  - INTRODUCTION: Atrial fibrillation (AF) is the most common arrhythmia and is
      associated with significant morbidity and mortality. The impact of matrix
      metalloproteinases (MMPs) on structural atrial remodeling and sustainment of AF
      in patients with persistent and permanent AF is unresolved. OBJECTIVES: The aim
      was to evaluate MMP-9 and its tissue inhibitor-1 (TIMP-1) as markers of atrial
      remodeling in patients with persistent AF (PAF) who underwent electrical
      cardioversion (ECV) and in patients with permanent AF (continuous AF, CAF).
      PATIENTS AND METHODS: Plasma levels of MMP-9 and TIMP-1, clinical findings, and
      echocardiographic parameters were evaluated in 39 patients with AF and in 14
      controls with sinus rhythm. RESULTS: The concentrations of MMP-9 were
      significantly higher in patients with PAF and CAF compared to controls. There was
      a significant increase of MMP-9 after ECV in the persistent AF group. The values
      of TIMP-1 were not significantly different between the groups. In patients with
      AF, MMP-9 levels were positively related to posterior wall thickness of the LV
      (r=0.356, P=0.049) and body mass index (r=0.367, P=0.046). CONCLUSION: Elevated
      levels of MMP-9 were related to the occurrence and maintenance of AF. This
      suggests that MMP-9 can be a marker of atrial remodeling in patients with AF.
      Regulation of the extracellular collagen matrix might be a potential therapeutic
      target in AF.

PMID- 25869466
TI  - [An exceptional case of tricuspid infective endocarditis due to Bartonella
      henseale revealed by an old pulmonary embolism].
AB  - We report a case of blood culture-negative tricuspid infective endocarditis
      revealed after tick bite by repeated pulmonary infection during one year due to
      septic pulmonary emboli in a 67-year-old farmer woman. Tricuspid vegetation and
      pulmonary emboli are calcified. Lyme serology is negative. Serologic test and PCR
      analysis are positive to Bartonella henselae. The evolution is favorable after
      antibiotic and anticoagulant treatment. Infective endocarditis due to B. henselae
      is an exceptional complication of cat scratch disease. You have to think about in
      case of blood culture-negative endocarditis with calcified valvular lesions even
      without cat bite, tick seems to be vector of the bacteria. 

PMID- 25869467
TI  - Comparative study of the efficacy of topical steroid and antibiotic combination
      therapy versus oral antibiotic alone when treating acute rhinosinusitis.
AB  - BACKGROUND: Acute rhinosinusitis arises as a consequence of viral rhinitis, and
      bacterial infection can subsequently occur. Intranasal antibiotics as an adjunct
      to corticosteroids usually demonstrate the greatest symptom relief. AIM: We
      wanted to clinically evaluate the effects of a topical antibiotic and steroid
      combination administered intranasally, versus an oral antibiotic alone when
      treating acute rhinosinusitis. METHOD: Forty patients with acute bacterial
      rhinosinusitis were divided into two groups. Group A received an antibiotic and
      steroid combination (ofloxacin 0.26 per cent and dexamethasone 0.053 per cent
      nasal drops) for 10 days, administered intranasally (5 drops in each nostril/8
      hours). Group B, the control group, received an oral antibiotic alone
      (amoxicillin 90 mg/kg). RESULTS: Eight hours after commencing treatment, facial
      pain was more severe in group B and nasal obstruction was reduced in both groups.
      Ten days after commencing treatment, anterior nasal discharge was 0.15 per cent
      in group A and absent in group B. CONCLUSION: The application of a topical
      antibiotic and steroid combination into the nasal cavity is an effective way of
      treating uncomplicated, acute bacterial rhinosinusitis with the theoretical
      advantages of easy administration, high local drug concentration and minimal
      systemic adverse effects.

PMID- 25869468
TI  - Recent advancement of molecular mechanisms of liver fibrosis.
AB  - Liver fibrosis occurs in response to any etiology of chronic liver injury
      including hepatitis B and C, alcohol consumption, fatty liver disease,
      cholestasis, and autoimmune hepatitis. Hepatic stellate cells (HSCs) are the
      primary source of activated myofibroblasts that produce extracellular matrix
      (ECM) in the liver. Various inflammatory and fibrogenic pathways contribute to
      the activation of HSCs. Recent studies also discovered that liver fibrosis is
      reversible and activated HSCs can revert to quiescent HSCs when causative agents
      are removed. Although the basic research for liver fibrosis has progressed
      remarkably, sensitive and specific biomarkers as non-invasive diagnostic tools,
      and effective anti-fibrotic agents have not been developed yet. This review
      highlights the recent advances in cellular and molecular mechanisms of liver
      fibrosis, especially focusing on origin of myofibroblasts, inflammatory
      signaling, autophagy, cellular senescence, HSC inactivation, angiogenesis, and
      reversibility of liver fibrosis.

PMID- 25869469
TI  - [Finger injuries in ball sports].
AB  - Ball sports are the most frequent cause of sport injuries and 60% of all hand
      injuries involve the fingers. The most common injury is closed rupture of the
      extensor tendon of the distal interphalangeal joint (mallet finger). Rupture of
      the deep flexor tendon (jersey finger) occurs particularly in contact ball
      sports, such as rugby. Injuries of the proximal interphalangeal and
      metacarpophalangeal joints are of high functional relevance. These injuries
      frequently represent complex lesions which are demanding both in diagnostics and
      therapy. Errors in diagnosis or insufficient treatment can lead to misalignment
      and functional impairment of the hand. This article provides an overview of the
      current treatment strategies and includes recommendations for the treatment of
      professional athletes.

PMID- 25869470
TI  - Distinct effects of prefrontal and parietal cortex inactivations on an
      accumulation of evidence task in the rat.
AB  - Numerous brain regions have been shown to have neural correlates of gradually
      accumulating evidence for decision-making, but the causal roles of these regions
      in decisions driven by accumulation of evidence have yet to be determined. Here,
      in rats performing an auditory evidence accumulation task, we inactivated the
      frontal orienting fields (FOF) and posterior parietal cortex (PPC), two rat
      cortical regions that have neural correlates of accumulating evidence and that
      have been proposed as central to decision-making. We used a detailed model of the
      decision process to analyze the effect of inactivations. Inactivation of the FOF
      induced substantial performance impairments that were quantitatively best
      described as an impairment in the output pathway of an evidence accumulator with
      a long integration time constant (>240 ms). In contrast, we found a minimal role
      for PPC in decisions guided by accumulating auditory evidence, even while finding
      a strong role for PPC in internally-guided decisions. 

PMID- 25869472
TI  - Moral Distress in Pediatric Healthcare Providers.
AB  - Pediatric providers across professions and clinical settings experience moral
      distress. Higher moral distress correlates with intent to leave for all
      professionals. Physicians as professional group had the highest moral distress.
      Intensive care nurses had the highest moral distress for nurses. While all
      providers describe distressing scenarios as disturbing, physicians report
      situations as occurring more frequently. The most distressing situations include
      requests for aggressive treatments not in child's best interest, poor team
      communication and lack of provider continuity. Understanding moral distress as
      experienced by all pediatric providers is needed to create interventions with a
      goal of reducing provider turnover. 

PMID- 25869471
TI  - Inhibitory activities of short linear motifs underlie Hox interactome specificity
      in vivo.
AB  - Hox proteins are well-established developmental regulators that coordinate cell
      fate and morphogenesis throughout embryogenesis. In contrast, our knowledge of
      their specific molecular modes of action is limited to the interaction with few
      cofactors. Here, we show that Hox proteins are able to interact with a wide range
      of transcription factors in the live Drosophila embryo. In this context,
      specificity relies on a versatile usage of conserved short linear motifs (SLiMs),
      which, surprisingly, often restrains the interaction potential of Hox proteins.
      This novel buffering activity of SLiMs was observed in different tissues and
      found in Hox proteins from cnidarian to mouse species. Although these
      interactions remain to be analysed in the context of endogenous Hox regulatory
      activities, our observations challenge the traditional role assigned to SLiMs and
      provide an alternative concept to explain how Hox interactome specificity could
      be achieved during the embryonic development. 

PMID- 25869473
TI  - New treatment modalities for hepatocellular cancer.
AB  - Heptatocellular (HCC) is a rapidly progressive fatal malignancy often presenting
      at an advanced stage at the time of initial diagnosis. Loco-regional therapies
      for early-stage HCC including surgical options (surgical resection and liver
      transplant) and percutaneous ablations could be potentially curative. Recent
      technological advances in percutaneous image-guided ablations have provided
      clinicians with a range of options which have proven to be equal to or better
      than surgical resection. For intermediate- and advanced-stage HCC, palliative
      therapies are available which significantly increase overall and progression-free
      survival. These palliative therapies include intra-arterial chemo- or
      radioembolization as monotherapy or in combination with percutaneous ablation or
      antiangiogenic drugs. Availability of a multitude of treatment options for
      various stages of HCC as well as conflicting data comparing their safety and
      efficacy presented in the several randomized controlled trials poses a
      significant challenge to hepatologists, surgeons, and interventional radiologists
      in selecting optimal therapy for their patients. The aim of this article is to
      review and discuss currently available therapies at each stage of HCC along with
      presenting clinical data published in most recent and relevant randomized
      controlled trials. 

PMID- 25869474
TI  - Lithiation of silicon nanoparticles confined in carbon nanotubes.
AB  - Silicon has the highest theoretical lithium storage capacity of all materials at
      4200 mAh/g; therefore, it is considered to be a promising candidate as the anode
      of high-energy-density lithium-ion batteries (LIBs). However, serious volume
      changes caused by lithium insertion/deinsertion lead to a rapid decay of the
      performance of the Si anode. Here, a Si nanoparticle (NP)-filled carbon nanotube
      (CNT) material was prepared by chemical vapor deposition, and a nanobattery was
      constructed inside a transmission electron microscope (TEM) using the Si NP
      filled CNT as working electrode to directly investigate the structural change of
      the Si NPs and the confinement effect of the CNT during the lithiation and
      delithiation processes. It is found that the volume expansion (~180%) of the
      lithiated Si NPs is restricted by the wall of the CNTs and that the CNT can
      accommodate this volume expansion without breaking its tubular structure. The Si
      NP-filled CNTs showed a high reversible lithium storage capacity and desirable
      high rate capability, because the pulverization and exfoliation of the Si NPs
      confined in CNTs were efficiently prevented. Our results demonstrate that filling
      CNTs with high-capacity active materials is a feasible way to make high
      performance LIB electrode materials, taking advantage of the unique confinement
      effect and good electrical conductivity of the CNTs. 

PMID- 25869475
TI  - Melanoma cell adhesion molecule-positive CD8 T lymphocytes mediate central
      nervous system inflammation.
AB  - OBJECTIVE: Although Tc17 lymphocytes are enriched in the central nervous system
      (CNS) of multiple sclerosis (MS) subjects and of experimental autoimmune
      encephalomyelitis (EAE) animals, limited information is available about their
      recruitment into the CNS and their role in neuroinflammation. Identification of
      adhesion molecules used by autoaggressive CD8(+) T lymphocytes to enter the CNS
      would allow further characterization of this pathogenic subset and could provide
      new therapeutic targets in MS. We propose that melanoma cell adhesion molecule
      (MCAM) is a surface marker and adhesion molecule used by pathogenic CD8(+) T
      lymphocytes to access the CNS. METHODS: Frequency, phenotype, and function of
      MCAM(+) CD8(+) T lymphocytes was characterized using a combination of ex vivo, in
      vitro, in situ, and in vivo approaches in humans and mice, including healthy
      controls, MS subjects, and EAE animals. RESULTS: Herein, we report that MCAM is
      expressed by human effector CD8(+) T lymphocytes and it is strikingly upregulated
      during MS relapses. We further demonstrate that MCAM(+) CD8(+) T lymphocytes
      express more interleukin 17, interferon gamma, granulocyte-macrophage colony
      stimulating factor, and tumor necrosis factor than MCAM(-) lymphocytes, and
      exhibit an enhanced killing capacity toward oligodendrocytes. MCAM blockade
      restricts the transmigration of CD8(+) T lymphocytes across human blood-brain
      barrier endothelial cells in vitro, and blocking or depleting MCAM in vivo
      reduces chronic neurological deficits in active, transfer, and spontaneous
      progressive EAE models. INTERPRETATION: Our data demonstrate that MCAM identifies
      encephalitogenic CD8(+) T lymphocytes, suggesting that MCAM could represent a
      biomarker of MS disease activity and a valid target for the treatment of
      neuroinflammatory conditions.

PMID- 25869477
TI  - Solitary pituitary metastasis from HER2-positive breast cancer.
AB  - The introduction of anti-HER2 therapy with trastuzumab has seen an increase in
      frequency of central nervous system metastasis as the site of first recurrence.
      Here, we present a rare case of a 63-year-old woman who presented with an
      isolated breast carcinoma pituitary metastasis 5 years following treatment for a
      high-risk breast cancer. This report underscores the changing nature of HER2
      positive disease in the post-trastuzumab era.

PMID- 25869476
TI  - Delivery of Phenamil Enhances BMP-2-Induced Osteogenic Differentiation of Adipose
      Derived Stem Cells and Bone Formation in Calvarial Defects.
AB  - Bone morphogenetic proteins (BMPs) have been widely used for bone repair in the
      craniofacial region. However, its high dose requirement in clinical applications
      revealed adverse effects and inefficient bone formation, along with high cost.
      Here, we report a novel osteoinductive strategy to effectively complement the
      osteogenic activity of BMP-2 using phenamil, a small molecule that can induce
      osteogenic differentiation via stimulation of BMP signaling. Treatment of adipose
      derived stem cells (ASCs) with BMP-2 in combination with phenamil significantly
      promoted the in vitro osteogenic differentiation of ASCs. The efficacy of the
      combination strategy of phenamil+BMP-2 was further confirmed in a mouse calvarial
      defect model using scaffolds consisting of poly(lactic-co-glycolic acid) and
      apatite layer on their surfaces designed to slowly release phenamil and BMP-2.
      Six weeks after implantation, the scaffolds treated with phenamil+BMP-2
      significantly promoted mouse calvarial regeneration as demonstrated by micro
      computerized tomography and histology, compared with the groups treated with
      phenamil or BMP-2 alone. Moreover, the combination treatment reduced the BMP-2
      dose without compromising calvarial healing efficacy. These results suggest
      promising complementary therapeutic strategies for bone repair in more efficient
      and cost-effective manners.

PMID- 25869478
TI  - Serum periostin in smokers and never smokers with asthma.
AB  - BACKGROUND: Elevated serum periostin is associated with airway eosinophilia and
      may predict response to therapies targeting Th2 inflammation. Smoking in asthma
      is generally associated with non-eosinophilic airway inflammation and
      corticosteroid insensitivity. We determined the effect of smoking status on serum
      periostin in asthma. METHODS: Serum periostin (ELISA; Aviscera Bioscience) was
      measured in 107 patients with stable asthma of different disease severity and 45
      healthy controls. The effects on serum periostin of clinical indices including
      smoking status and of inflammatory biomarkers including sputum eosinophil count
      were analysed. Serum periostin was measured before and after two weeks of oral
      corticosteroids in a separate group of 33 non-smokers and smokers with stable
      asthma. RESULTS: Serum periostin (median [IQR], ng/mL) was reduced in smokers
      with asthma compared to never smokers with asthma; 9 (9, 307) versus 233 (34,
      1108) respectively, p = 0.017. Periostin was not influenced by disease severity
      (p = 0.786) or atopic status (p = 0.144). There was a weak correlation between
      serum periostin and sputum eosinophil count in smokers with asthma (r = 0.315, p
      = 0.020). The proportion of patients with an elevated serum periostin
      concentration was greater in never smokers with asthma compared to smokers with
      asthma [65% versus 39% respectively, p = 0.003]. Oral steroid treatment reduced
      serum periostin (p = 0.030) in non-smokers with asthma. CONCLUSION: Despite lower
      median serum periostin concentrations in smokers with asthma compared to never
      smokers with asthma, approximately forty percent of this group had a high level.
      The potential value of a raised serum periostin concentration in predicting a
      beneficial response to therapies targeting Th2 inflammation in smokers with
      asthma requires to be investigated.

PMID- 25869479
TI  - The effects of enteral glutamine on radiotherapy induced dermatitis in breast
      cancer.
AB  - PURPOSE: Radiotherapy is a critical component of breast cancer treatment. Many
      skin reactions ranging from erythema to moist desquamation and ulceration can be
      induced by high dose external beam radiotherapy. There is no golden standard for
      treating radiation dermatitis. Glutamine is an amino acid which improved wound
      healing through its anabolic effects and improvements in wound matrix formation
      in burn patients. We designed a study to show effects of glutamine in radiation
      induced dermatitis. MATERIAL AND METHOD: Forty patients who received radiotherapy
      for breast cancer were randomized into 2 groups. In group 1 the patients were
      treated with 15 gr of enteral glutamine whereas the patients in group 2 were
      treated with placebo. The radiation induced skin reactions were evaluated in both
      groups. RESULTS: In glutamine treated group 88, 9% of patients developed grade I
      toxicity comparing to 80% of patients in placebo group developed grade II
      toxicity. This difference between the groups was statistically significant. (p <
      0.001) CONCLUSION: Enteral glutamine minimizes radiation induced dermatitis.

PMID- 25869480
TI  - Leptin intake in suckling rats restores altered T3 levels and markers of adipose
      tissue sympathetic drive and function caused by gestational calorie restriction.
AB  - BACKGROUND: Maternal calorie restriction during gestation in rats has been
      associated with altered white adipose tissue (WAT) sympathetic innervation and
      function in offspring. Here, we aimed to investigate whether supplementation with
      oral leptin (a breast milk component) throughout the lactation period may revert
      the aforementioned adverse programming effects. METHODS: Three groups of male and
      female rats were studied at the postnatal day 25: the offspring of control dams,
      the offspring of 20% calorie-restricted dams during pregnancy (CR) and CR rats
      supplemented with physiological doses of leptin throughout lactation (CR-Leptin).
      Tyrosine hydroxylase (TH) levels and its immunoreactive area, and mRNA expression
      levels of lipid metabolism-related genes and of deiodinase iodothyronine type II
      (Dio2) were determined in WAT. Triiodothyronine (T3) levels were determined in
      the blood. RESULTS: In CR males, leptin treatment restored the decreased TH
      levels and its immunoreactive area in WAT, and partially normalized expression
      levels of genes related to lipolysis and fatty acid oxidation (adipose
      triglyceride lipase, hormone-sensitive lipase, carnitine palmitoyltransferase 1b
      and peroxisome proliferator-activated receptor gamma coactivator 1-alpha). Leptin
      treatment also reverted the decreased T3 plasma levels and WAT lipoprotein lipase
      mRNA levels occurring in CR males and females, and the decreased Dio2 mRNA levels
      in CR females. CONCLUSIONS: Leptin supplementation throughout the lactation
      period reverts the malprogrammed effects on WAT structure and function induced by
      undernutrition during pregnancy. These findings support the relevance of the
      intake of leptin during lactation, bearing clear characteristics of essential
      nutrient, and provide a strategy to treat and/or prevent the programmed trend to
      obesity acquired by inadequate fetal nutrition.

PMID- 25869481
TI  - TURN: A Simple Predictor of Symptomatic Intracerebral Hemorrhage After IV
      Thrombolysis.
AB  - BACKGROUND: IV Thrombolysis (rt-PA) for ischemic stroke treatment carries a
      substantial risk for symptomatic intracerebral hemorrhage (sICH). Our purpose was
      to develop a computationally simple and accurate sICH predictor METHODS : Our
      derivation dataset consisted of 210 ischemic stroke patients receiving IV rt-PA
      from January 2009 until July 2013 at Yale-New Haven Hospital. Our validation
      dataset included 303 patients who received IV rt-PA during the NINDS rt-PA trial.
      Independent sICH predictors were identified by logistic regression and combined
      to form the TURN score. Predictive ability and goodness of fit were quantified by
      odds ratios (OR) and areas under the receiver operating characteristic curve
      (AUROC). RESULTS: 3 out of 17 clinical parameters were identified as independent
      predictors of sICH: prestroke mRS score (OR 1.54, P = 0.02), baseline NIHSS score
      (OR 1.13, P = 0.002), and platelet count (OR 0.99, P = 0.04). We combined these
      three parameters to form the TURNP score. For added simplicity, prestroke mRS
      score and baseline NIHSS score alone were also combined to form the TURN score,
      and predicted sICH without a significant drop in OR or AUROC. CONCLUSIONS: We
      developed a new score for predicting sICH after IV thrombolysis. Our score is
      simple and with acceptable accuracy, making it ideal for use in the hyperacute
      stroke setting.

PMID- 25869482
TI  - Quantifying amyloid fibrils in protein mixtures via infrared attenuated-total
      reflection spectroscopy.
AB  - Amyloid aggregation of proteins is usually associated with amyloid diseases. A
      distinct feature of protein aggregation is the increase of crossed beta-sheet
      structures. Infrared attenuated-total-reflectance (IR-ATR) spectroscopy is a
      sensitive optical technique that has the potential to provide secondary structure
      characteristics of proteins even in complex biological samples. In this study we
      report the analysis of secondary structures of proteins, using the amide I band
      for the detection and quantification of amyloid fibrils in protein mixtures by
      use of IR-ATR techniques, at comparatively low sample concentrations. From the
      experimental results, an analytical model of the relationship between the IR
      spectra of protein mixtures and the individual mixture components was established
      using spectral-deconvolution procedures and curve-fitting methods. On the basis
      of this model, four ratios were shown to provide direct information on amyloid
      aggregated fibrils via the increase of crossed beta-sheet structures in protein
      mixture samples. In conclusion, this study confirms the utility of IR
      spectroscopy for analyzing protein mixtures and for identifying amyloid fibril
      information within such complex multi-component samples. 

PMID- 25869483
TI  - Detection of organic nanoparticles in human bone marrow-derived stromal cells
      using ToF-SIMS and PCA.
AB  - The detection and localization of polymer-based nanoparticles in human bone
      marrow-derived stromal cells (hBMSC) by time-of-flight secondary ion mass
      spectrometry (ToF-SIMS) is reported as an example for the mass spectrometry
      imaging of organic nanoparticles in cell environments. Polyelectrolyte complex
      (PEC) nanoparticles (NP) made of polyethylenimine (PEI) and cellulose sulfate
      (CS), which were developed as potential drug carrier and coatings for implant
      materials, were chosen for the imaging experiments. To investigate whether the
      PEI/CS-NP were taken up by the hBMSC ToF-SIMS measurements on cross sections of
      the cells and depth profiling of whole, single cells were carried out. Since the
      mass spectra of the PEI/CS nanoparticles are close to the mass spectra of the
      cells principal component analysis (PCA) was performed to get specific masses of
      the PEI/CS-NP. Mass fragments originating from the NP compounds especially from
      cellulose sulfate could be used to unequivocally detect and image the PEI/CS-NP
      inside the hBMSC. The findings were confirmed by light and transmission electron
      microscopy. Graphical Abstract During ToF-SIMS analysis Bi3 (+) primary ions hit
      the sample surface and so called secondary ions (SI) are emitted and detected in
      the mass analyser. Exemplary mass images of cross sections of human mesenchymal
      stromal cells (red; m/z = 86.1 u) cultured with organic nanoparticles (green; m/z
      = 143.0 u) were obtained. 

PMID- 25869484
TI  - Fluorescence dye-based detection of mAb aggregates in CHO culture supernatants.
AB  - Product yields, efficacy, and safety of monoclonal antibodies (mAbs) are reduced
      by the formation of higher molecular weight aggregates during upstream
      processing. In-process characterization of mAb aggregate formation is a challenge
      since there is a lack of a fast detection method to identify mAb aggregates in
      cell culture. In this work, we present a rapid method to characterize mAb
      aggregate-containing Chinese hamster ovary (CHO) cell culture supernatants. The
      fluorescence dyes thioflavin T (ThT) and 4-4-bis-1-phenylamino-8-naphthalene
      sulfonate (Bis-ANS) enabled the detection of soluble as well as large mAb
      aggregates. Partial least square (PLS) regression models were used to evaluate
      the linearity of the dye-based mAb aggregate detection in buffer down to a mAb
      aggregate concentration of 2.4 MUg mL(-1). Furthermore, mAb aggregates were
      detected in bioprocess medium using Bis-ANS and ThT. Dye binding to aggregates
      was stable for 60 min, making the method robust and reliable. Finally, the
      developed method using 10 MUmol L(-1) Bis-ANS enabled discrimination between CHO
      cell culture supernatants containing different levels of mAb aggregates. The
      method can be adapted for high-throughput screening, e.g., to screen for cell
      culture conditions influencing mAb product quality, and hence can contribute to
      the improvement of production processes of biopharmaceuticals in mammalian cell
      culture. 

PMID- 25869485
TI  - Enantioselective analysis of non-steroidal anti-inflammatory drugs in freshwater
      fish based on microextraction with a supramolecular liquid and chiral liquid
      chromatography-tandem mass spectrometry.
AB  - Toxicity of pharmaceuticals to aquatic biota is still largely unknown, and no
      research on the stereoselective toxicity of chiral drugs to these organisms has
      been undertaken to date. Because of the lack of analytical methods available for
      this purpose, this manuscript deals, for the first time, with the
      enantioselective analysis of the non-steroidal anti-inflammatory drugs (NSAIDs)
      ibuprofen, naproxen and ketoprofen in freshwater fish. The method was based on
      the microextraction of NSAIDs from fish muscle with a supramolecular liquid made
      up of inverted hexagonal aggregates of decanoic acid, their enantiomeric
      separation by liquid chromatography onto a (R)-1-naphthylglycine and 3,5
      dinitrobenzoic acid stationary phase and quantification by tandem mass
      spectrometry. Limits of quantitation (LOQs) for NSAID enantiomers were in the
      range 1.7-3.3 ng g(-1). Absolute recoveries were from 97 to 104 %, which
      indicated the high extraction efficiency of the supramolecular solvent.
      Extraction equilibrium conditions were reached after 10 min which permitted fast
      sample treatment. Relative standard deviations for enantiomers in fish muscle
      were always below 6 %. Isotopically labelled internal standards were used to
      compensate for matrix interferences. The method in-house validation was carried
      out with the Oncorhynchus mykiss species, and it was applied to the determination
      of NSAID enantiomers in different fortified freshwater fish species (Alburnus
      alburnus, Lepomis gibbosus, Micropterus salmoides, O. mykiss and Cyprinus
      carpio).

PMID- 25869486
TI  - Editorial: Potential Therapeutic Agents based on DNA Sequence- Selective Binding
      Substances.

PMID- 25869487
TI  - Time- and dose-dependent effects of total-body ionizing radiation on muscle stem
      cells.
AB  - Exposure to high levels of genotoxic stress, such as high-dose ionizing
      radiation, increases both cancer and noncancer risks. However, it remains
      debatable whether low-dose ionizing radiation reduces cellular function, or
      rather induces hormetic health benefits. Here, we investigated the effects of
      total-body gamma-ray radiation on muscle stem cells, called satellite cells.
      Adult C57BL/6 mice were exposed to gamma-radiation at low- to high-dose rates
      (low, 2 or 10 mGy/day; moderate, 50 mGy/day; high, 250 mGy/day) for 30 days. No
      hormetic responses in proliferation, differentiation, or self-renewal of
      satellite cells were observed in low-dose radiation-exposed mice at the acute
      phase. However, at the chronic phase, population expansion of satellite cell
      derived progeny was slightly decreased in mice exposed to low-dose radiation.
      Taken together, low-dose ionizing irradiation may suppress satellite cell
      function, rather than induce hormetic health benefits, in skeletal muscle in
      adult mice. 

PMID- 25869488
TI  - Mistic-fused expression of algal rhodopsins in Escherichia coli and its
      photochemical properties.
AB  - BACKGROUND: Since algal rhodopsins, the eukaryotic seven-transmembrane proteins,
      are generally difficult to express in Escherichia coli, eukaryotic cells have
      been used for heterologous expression. Mistic, a membrane-associated protein that
      was originally discovered in Bacillus subtilis, has been shown to improve the
      expression levels of many foreign integral membrane proteins in E. coli when used
      as a fusion partner linked to the N-terminus of cargo proteins. METHODS: Here, we
      expressed two algal rhodopsins with N- and C-terminal Mistic domains in E. coli
      Acetabularia rhodopsin I (ARI) and Chlamydomonas sensory rhodopsin B (CSRB,
      channel rhodopsin 2). UV/VIS spectroscopy, pH titration of proton acceptor
      residue, laser-induced photolysis and electrophysiological measurement were used
      for investigating important residues in proton transport and spectroscopic
      characters of the proteins. RESULTS: Protein yield of two algal rhodopsins was
      enhanced, obtaining 0.12mg of Mistic-ARI and 0.04mg of Mistic-CSRB per liter of
      culture. Spheroplast expression Mistic-ARI had outward proton-pumping activity,
      indicating protein functionality. Asp89 of ARI changed its protonation state by
      light absorption, and Asp100 was important for O(600) formation.
      Electrophysiology revealed that both residues took part in proton transport. The
      spectroscopic analyses of Mistic-CSRB revealed its characteristics. CONCLUSIONS:
      Fusion to the membrane-integrating protein Mistic can enhance overexpression of
      eukaryotic type I rhodopsins in E. coli. GENERAL SIGNIFICANCE: These findings
      indicate that Mistic fusion and E. coli expression method could be an effective,
      low cost technique for studying eukaryotic membrane proteins. This may have
      useful implications, for example, in studying structural characteristics and
      optogenetics for rhodopsins.

PMID- 25869489
TI  - Gelatinase A (MMP-2) promotes murine adipogenesis.
AB  - BACKGROUND: Expansion of adipose tissue is dependent on adipogenesis,
      angiogenesis and extracellular matrix remodeling. A functional role in these
      processes was suggested for the gelatinase subfamily of the matrix
      metalloproteinases. Here, we have evaluated a potential role of gelatinase A (MMP
      2) in adipogenesis. METHODS: Murine embryonic fibroblasts (MEF) were derived from
      wild-type or MMP-2 deficient mice. Genetic manipulation of Mmp2 (shRNA-knockdown
      or overexpression) was performed in 3T3-F442A preadipocytes. Cell cultures were
      subjected to an adipogenic medium. As an in vivo model for de novo adipogenesis,
      3T3-F442A preadipocytes with or without knockdown were injected subcutaneously in
      Nude BALB/c mice kept on high fat diet. RESULTS: Mmp2 deficient MEF, as compared
      to controls, showed significantly impaired differentiation into mature
      adipocytes, as demonstrated by 90% reduced intracellular lipid content and
      reduced expression of pro-adipogenic markers. Moreover, selective Mmp2 knockdown
      in 3T3-F442A preadipocytes resulted in significantly reduced differentiation. In
      contrast, overexpression of Mmp2 resulted in markedly enhanced differentiation.
      In de novo formed fat pads resulting from preadipocytes with Mmp2 knockdown
      expression of aP2, Ppar-gamma and adiponectin was significantly lower, and
      collagen was more preserved. The fat pad weights as well as size and density of
      adipocytes or blood vessels were, however, not significantly different from
      controls. CONCLUSION: Our data directly support a functional role of MMP-2 in
      adipogenesis in vitro, and suggest a potential role in in vivo adipogenesis.
      GENERAL SIGNIFICANCE: Selective modulation of MMP-2 levels affects adipogenesis.

PMID- 25869490
TI  - Mannose-recognition mutant of the galactose/N-acetylgalactosamine-specific C-type
      lectin CEL-I engineered by site-directed mutagenesis.
AB  - BACKGROUND: CEL-I is a galactose/N-acetylgalactosamine-specific C-type lectin
      isolated from the sea cucumber Cucumaria echinata. Its carbohydrate-binding site
      contains a QPD (Gln-Pro-Asp) motif, which is generally recognized as the
      galactose specificity-determining motif in the C-type lectins. In our previous
      study, replacement of the QPD motif by an EPN (Glu-Pro-Asn) motif led to a weak
      binding affinity for mannose. Therefore, we examined the effects of an additional
      mutation in the carbohydrate-binding site on the specificity of the lectin.
      METHODS: Trp105 of EPN-CEL-I was replaced by a histidine residue using site
      directed mutagenesis, and the binding affinity of the resulting mutant, EPNH-CEL
      I, was examined by sugar-polyamidoamine dendrimer assay, isothermal titration
      calorimetry, and glycoconjugate microarray analysis. Tertiary structure of the
      EPNH-CEL-I/mannose complex was determined by X-ray crystallographic analysis.
      RESULTS: Sugar-polyamidoamine dendrimer assay and glycoconjugate microarray
      analysis revealed a drastic change in the specificity of EPNH-CEL-I from
      galactose/N-acetylgalactosamine to mannose. The association constant of EPNH-CEL
      I for mannose was determined to be 3.17*10(3) M(-1) at 25 degrees C. Mannose
      specificity of EPNH-CEL-I was achieved by stabilization of the binding of mannose
      in a correct orientation, in which the EPN motif can form proper hydrogen bonds
      with 3- and 4-hydroxy groups of the bound mannose. CONCLUSIONS: Specificity of
      CEL-I can be engineered by mutating a limited number of amino acid residues in
      addition to the QPD/EPN motifs. GENERAL SIGNIFICANCE: Versatility of the C-type
      carbohydrate-recognition domain structure in the recognition of various
      carbohydrate chains could become a promising platform to develop novel molecular
      recognition proteins.

PMID- 25869492
TI  - Incidence of hemoglobinopathies and thalassemias in Northern Alberta.
      Establishment of reference intervals for HbF and HbA2.
AB  - OBJECTIVES: The aims of this study were to identify the incidence of
      hemoglobinopathies and thalassemias in Northern Alberta and calculate the
      reference intervals (RI) for hemoglobin (Hb) HbF and HbA2. METHODS: A
      retrospective ad-hoc analysis of the structural Hb variants and thalassemias
      identified on patients who had a hemoglobinopathy/thalassemia investigation
      performed between February 1 to December 31, 2013. Results were extracted from
      the Laboratory Information System. Statistical analysis was performed using
      MedCalc(r) version 11.4.2.0 for Windows software. RESULTS: 6616
      hemoglobinopathy/thalassemia investigations and HbS screens were physician
      requested and 602 Hb variants were fortuitously found during HbA1c analysis. 3438
      were interpreted as "normal" and 532 were classified as iron deficient. 3306
      individuals, with age ranging from 3 to 92 years were included in the RI
      calculation. HbA2 RI was 2.3% to 3.4% and HbF 0.0% to 1.8%. 524 and 423 alpha and
      beta thalassemia traits respectively were identified. Additionally ten deltabeta
      thalassemia traits and twelve cases of HbH disease were identified. Regarding
      hemoglobinopathies, 7% were classified as alpha-chain variants and 93% as beta
      chain variants with HbS (46%), HbE (16%), HbD Punjab (8%) and HbC (7%) traits
      being the most prevalent. We also documented 20 homozygous hemoglobinopathies and
      36 compound/double heterozygous hemoglobinopathies. CONCLUSION: A wide diversity
      of hemoglobinopathies is found in the Northern Alberta population, 80% of the
      hemoglobinopathies were found as a reflex to HbA1c testing. Reference intervals
      for HbF and HbA2 were established.

PMID- 25869491
TI  - Closure of mitochondrial potassium channels favors opening of the Tl(+)-induced
      permeability transition pore in Ca(2+)-loaded rat liver mitochondria.
AB  - It is known that a closure of ATP sensitive (mitoKATP) or BK-type Ca(2+)
      activated (mitoKCa) potassium channels triggers opening of the mitochondrial
      permeability transition pore (MPTP) in cells and isolated mitochondria. We found
      earlier that the Tl(+)-induced MPTP opening in Ca(2+)-loaded rat liver
      mitochondria was accompanied by a decrease of 2,4-dinitrophenol-uncoupled
      respiration and increase of mitochondrial swelling and DeltaPsimito dissipation
      in the medium containing TlNO3 and KNO3. On the other hand, our study showed that
      the mitoKATP inhibitor, 5-hydroxydecanoate favored the Tl(+)-induced MPTP opening
      in the inner membrane of Ca(2+)-loaded rat heart mitochondria (Korotkov et al.
      2013). Here we showed that 5-hydroxydecanoate increased the Tl(+)-induced MPTP
      opening in the membrane of rat liver mitochondria regardless of the presence of
      mitoKATP modulators (diazoxide and pinacidil). This manifested in more pronounced
      decrease in the uncoupled respiration and acceleration of both the swelling and
      the DeltaPsimito dissipation in isolated rat liver mitochondria, incubated in the
      medium containing TlNO3, KNO3, and Ca(2+). A slight delay in Ca(2+)-induced
      swelling of the mitochondria exposed to diazoxide could be result of an
      inhibition of succinate oxidation by the mitoKATP modulator. Mitochondrial
      calcium retention capacity (CRC) was markedly decreased in the presence of the
      mitoKATP inhibitor (5-hydroxydecanoate) or the mitoKCa inhibitor (paxilline). We
      suggest that the closure of mitoKATP or mitoKCa in calcium loaded mitochondria
      favors opening of the Tl(+)-induced MPTP in the inner mitochondrial membrane. 

PMID- 25869493
TI  - Does the addition of RDW improve current ICU scoring systems?
AB  - BACKGROUND: The aim of this study was to evaluate whether the addition of red
      blood cell distribution width (RDW) improves the prognostic value of current
      intensive care unit (ICU) scoring systems, namely APACHE III. DESIGN AND METHODS:
      All patients admitted to a mixed ICU in Brisbane between June 2013 and July 2014
      for whom RDW was available were included in the study. Analyses included
      descriptive statistics, linear regression correlation, and receiver operating
      characteristic (ROC) curves. RESULTS: The study included 708 patients for whom
      both ICU mortality prediction and RDW were available. In univariate analysis
      higher RDW values were associated with increased hospital mortality. Adding RDW
      to APACHE III increased the area under the ROC marginally (from 0.9586 to
      0.9613). RDW was not correlated with C-reactive protein, white cell count, or
      patient's length of stay in ICU. CONCLUSION: RDW was an independent predictor of
      mortality. The addition of RDW to APACHE III improved its mortality prediction
      marginally. The underlying mechanism of RDW elevation warrants further
      investigation.

PMID- 25869494
TI  - Subjective need for psychological support (PsySupp) in parents of children and
      adolescents with disorders of sex development (dsd).
AB  - Disorders/diversity of sex development (dsd) is an umbrella term for congenital
      conditions often diagnosed within childhood. As most parents are unprepared for
      this situation, psychological support (PsySupp) is recommended. The aim of this
      study was to analyse the extent to which parents express a need for PsySupp.
      Three hundred twenty-nine parents of children with dsd were included; 40.4 % of
      the parents indicated to have a need for PsySupp, only 50 % of this group
      received it adequately. The diagnoses partial gonadal dysgenesis, partial
      androgen insensitivity syndrome (pAIS) and disorders of androgen synthesis are
      associated with a high need for PsySupp in parents (54, 65, and 50 %). Sex
      assignment surgery neither reduced nor increased the need for PsySupp. Taking a
      picture, radiography, laparoscopy, gonadal biopsy, gonadectomy and hormonal
      puberty induction are associated with a high need for PsySupp. There was no
      association between the need for PsySupp and the parents' perception of the
      appearance of the genitalia. CONCLUSION: Having a child with dsd is associated
      with a high need for PsySupp in parents. In particular, parents of children with
      XY-dsd with androgen effects other than hypospadias expressed a high need of
      PsySupp. PsySupp for parents should be an obligatory part of interdisciplinary
      care to reduce fears and concerns. What is known * In parents, having a child
      with dsd provokes insecurities and fears. Hence, psychological support is
      recommended as part of the interdisciplinary care. What is new * This is the
      first study investigating the subjective need for psychological support in a
      large sample of parents of children with dsd in Germany. We present data on the
      subjective need for psychological support of the parents, related diagnoses and
      factors, which should be considered in psychological counselling.

PMID- 25869497
TI  - The autonomic nervous system and cardiovascular disease: role of n-3 PUFAs.
AB  - In the last decades, a large body of experimental and clinical evidence has been
      accumulated showing that cardiovascular diseases are often accompanied by an
      imbalance in the sympathetic-vagal outflow to the heart, resulting in a chronic
      adrenergic activation. The arterial baroreceptor system is a key component of
      mechanisms contributing to the neural regulation of the cardiovascular system.
      Several methods have been proposed to assess autonomic activity by analyzing
      heart rate and blood pressure changes either spontaneously occurring or following
      provocations. The autonomic nervous system has been regarded as one of the
      putative mechanisms involved into the beneficial effects of exposure to n-3 fatty
      acids observed in epidemiological studies. The aim of the present review is to
      provide an update on the clinical evidence proposed so far linking exposure to n
      3 fatty acids to autonomic nervous system modulation. 

PMID- 25869495
TI  - An hour-specific transcutaneous bilirubin nomogram for Mongolian neonates.
AB  - Transcutaneous bilirubin (TcB) nomograms have been developed for different
      populations. However, the TcB level, rate of rise and peak varies among countries
      and ethnicities. The aim of this study was to establish an hour-specific TcB
      nomogram for healthy term and late preterm Mongolian neonates during the first
      144 h after birth. A total of 5084 TcB measurements from 1297 healthy neonates
      (gestational age >=35 weeks, birth weight >=2000 g) were obtained from October
      2012 to October 2013. All measurements were performed using the Jaundice Meter,
      the JM-103 at 6 to 144 postnatal hours. Mongolian infants had the following
      characteristics: 27.1 % were delivered by cesarean section, 17.8 % had a birth
      weight >4000 g, and >90 % were being breastfed. TcB percentiles for each
      designated time point were calculated for the development of an hour-specific
      nomogram. TcB levels increased most rapidly in the first 24 h and less rapidly
      from 24 to 78 h, reaching a plateau after 78 h for the 50th percentile. TcB
      levels of Mongolian neonates for each time point were higher than those of
      previous studies. CONCLUSION: The higher values of the TcB nomogram for Mongolian
      neonates may be due to their Asian ethnicity and exclusive breastfeeding. WHAT IS
      KNOWN: * TcB nomograms for neonatal jaundice screening have been established for
      many countries and ethnicities. The pattern of the TcB nomogram varies by country
      and ethnicity. What is New: * A TcB nomogram for neonates of Mongolian ethnicity
      at 6-144 postnatal hours was created and it had higher values than those in
      previous studies.

PMID- 25869496
TI  - Understanding Attendance in a Community-Based Parenting Intervention for
      Immigrant Latino Families.
AB  - Community-based participatory research (CBPR) can help increase the attendance in
      community programs. Padres Informados, Jovenes Preparados (PIJP) is a program
      that aims to prevent tobacco and other substance use among Latino youth by
      promoting positive parenting. Although the trial used CBPR approaches, attendance
      was inconsistent. In the present study, factors associated with attendance and
      nonattendance and recommendations to maximize participation were explored in 12
      brief feedback discussions (BFDs) with participants and in 10 in-depth interviews
      (IDIs) with facilitators who delivered PIJP. Content analysis guided two pairs of
      researchers, who independently coded emerging themes and categories (kappa = .86
      for BFDs and .73 for IDIs). Data from BFDs and IDIs were merged and interpreted
      together. We grouped factors that positively affected participation into three
      categories: individual and family (e.g., motivation), program (e.g., offering
      food and childcare and having facilitators who are trusted), and research (e.g.,
      having incentives). Barriers to participation were grouped into four categories:
      individual and family (e.g., family conflicts), sociocultural (e.g., community
      and cultural beliefs), program (e.g., fixed schedules), and research (e.g.,
      recruitment procedures). Participants provided recommendations to address all
      types of barriers. Although PIJP used CBPR, complete satisfaction of community
      needs is difficult. Effective community programs must address participants' needs
      and preferences. 

PMID- 25869498
TI  - A brief review on high on-aspirin residual platelet reactivity.
AB  - Although aspirin is effective in secondary prevention in coronary heart disease,
      new thromboembolic events in patients on aspirin are frequently seen. In trials
      on aspirin-treated patients, platelet function tests have revealed large
      variability in platelet aggregation. This phenomenon has been named aspirin
      resistance, aspirin non-responsiveness or high-on-aspirin residual platelet
      reactivity. The mechanism of aspirin antiplatelet effect is due to the inhibition
      of cyclooxygenase-1 enzyme in platelets. In some trials, almost all patients on
      aspirin have a very low level of serum thromboxane B2, indicating that the
      measured platelet reactivity in aspirin-treated patients might be due to platelet
      activation via other pathways, such as ADP or thrombin. The prevalence of real
      aspirin resistance seems to be very low, and probably the term "high-on-aspirin
      residual platelet reactivity" should be preferred to describe this phenomenon. 

PMID- 25869500
TI  - Vascular AMPK as an attractive target in the treatment of vascular complications
      of obesity.
AB  - The key for the survival of all organisms is the regulation and control of energy
      metabolism. Thus, several strategies have evolved in each tissue in order to
      balance nutrient supply with energy demand. Adenosine monophosphate-activated
      protein kinase (AMPK) is now recognized as a key participant in energy
      metabolism. It ensures an appropriate energetic supply by promoting energy
      conserving pathways in detriment of anabolic processes not essential for cell
      survival. Vascular AMPK plays a critical role in the regulation of blood flow and
      vascular tone through several mechanisms, including vasodilation by stimulating
      nitric oxide release in endothelial cells. Since obesity leads to endothelial
      damage and AMPK dysregulation, AMPK activation might be an important strategy to
      restore vascular function in cardiometabolic alterations. In the present review
      we focus on the role of vascular AMPK in both endothelial and smooth muscle
      cells, paying special attention to its dysregulation in obesity- and high-fat
      diet-related complications, as well as to the mechanisms and benefits of vascular
      AMPK activation. 

PMID- 25869499
TI  - Sparstolonin B suppresses rat vascular smooth muscle cell proliferation,
      migration, inflammatory response and lipid accumulation.
AB  - Vascular smooth muscle cells (VSMCs) play a crucial role in atherosclerotic
      lesion formation. Sparstolonin B (SsnB) is a TLR2/TLR4 antagonist that inhibits
      inflammatory responses in multiple cell types. Herein, we investigated if SsnB
      inhibited VSMC proliferation, migration, inflammatory response and lipid
      accumulation. We found that SsnB suppressed VSMC proliferation and migration
      induced by PDGF. SsnB significantly suppressed the expression of MCP-1, TNFalpha
      and IL-6 in VSMCs stimulated by either lipopolysaccharide (LPS) or PDGF. Erk1/2
      and Akt signaling pathways, which are responsible for the VSMC inflammatory
      response, were activated by LPS or PDGF stimulation, and SsnB significantly
      inhibited their activation. SsnB also substantially suppressed the intracellular
      cholesterol accumulation in VSMCs loaded with acetylated LDL. Mechanistically,
      SsnB remarkably repressed LPS-induced up-regulation of CD36, which is responsible
      for lipid uptake, and dramatically reversed LPS-induced inhibition of ABCA1,
      which promotes the efflux of intracellular free cholesterol. In conclusion, our
      results indicate that SsnB significantly inhibits VSMC proliferation, migration,
      inflammatory responses and lipid accumulation. Along with the previously reported
      anti-inflammatory activities of SsnB on macrophages and vascular endothelial
      cells, our data strongly suggest that SsnB may be developed as a new anti
      atherogenic therapy. 

PMID- 25869501
TI  - Corticotrophin-releasing factor participates in S1PR3-dependent cPLA2 expression
      and cell motility in vascular smooth muscle cells.
AB  - This work is to investigate the role of CRF receptors in VSMC migration and the
      relevant mechanisms. We studied the role of CRF receptors in cell motility and
      found that S1P signaling pathway is involved in the regulation of cPLA2 induced
      by CRF. S1P is synthesized by Sphk1 and Sphk2 and binds to five GPCR designated
      S1P1-5. We observed that activation of CRFR1 resulted in increased cell
      migration, whereas activation of CRFR2 resulted in decreased cell migration.
      cPLA2 and iPLA2 were knocked down respectively to explore the corresponding
      effect on cell migration by means of shRNA interference. cPLA2 expression was
      increased by CRFR1 but decreased by CRFR2. On the contrary, iPLA2 expression was
      inhibited by CRFR1 but enhanced by CRFR2. The regulation of cPLA2 was in line
      with the regulation of Sphk1 and hence cell migration after the activation of
      CRFR1 or CRFR2. Consistently, S1P release was enhanced with CRFR1 activation.
      Both DMS (Sphk inhibitor) and CAY10444 (S1PR3 inhibitor) attenuated cPLA2
      expression and thus decreased cell migration in response to CRF. In addition, CRF
      could not promote cell migration after S1PR3 silencing. Our results suggest the
      pro-migratory role of CRFR1-Sphk1-S1P-S1PR3-cPLA2 signaling pathway in VSMCs. 

PMID- 25869502
TI  - Exosomes and exosomal miRNAs in cardiovascular protection and repair.
AB  - Cell-cell communication between cardiac and vascular cells and from stem and
      progenitor cells to differentiated cardiovascular cells is both an important and
      complex process, achieved through a diversity of mechanisms that have an impact
      on cardiovascular biology, disease and therapeutics. In recent years, evidence
      has accumulated suggesting that extracellular vesicles (EVs) are a new system of
      intercellular communication. EVs of different sizes are produced via different
      biogenesis pathways and have been shown to be released and taken up by most of
      known cell types, including heart and vascular cells, and stem and progenitor
      cells. This review will focus on exosomes, the smallest EVs (up to 100nm in
      diameter) identified so far. Cells can package cargoes consisting of selective
      lipids, proteins and RNA in exosomes and such cargoes can be shipped to recipient
      cells, inducing expressional and functional changes. This review focuses on
      exosomes and microRNAs in the context of cardiovascular disease and repair. We
      will describe exosome biogenesis and cargo formation and discuss the available
      information on in vitro and in vivo exosomes-based cell-to-cell communication
      relevant to cardiovascular science. The methods used in exosome research will be
      also described. Finally, we will address the promise of exosomes as clinical
      biomarkers and their impact as a biomedical tool in stem cell-based
      cardiovascular therapeutics. 

PMID- 25869503
TI  - Roles of ROS and PKC-betaII in ionizing radiation-induced eNOS activation in
      human vascular endothelial cells.
AB  - Vascular endothelial cells can absorb higher radiation doses than any other
      tissue in the body, and post-radiation impaired endothelial nitric oxide synthase
      (eNOS) function may be developed as a potential contributor to the pathogenesis
      of vascular injury. In this study, we investigated early alterations of eNOS
      signaling in human umbilical venous endothelial cells (HUVECs) exposed to X-ray
      radiation. We found that ionizing radiation increased eNOS phosphorylation at Ser
      1177 and dephosphorylation at Thr-495 in HUVECs in a dose-dependent (<= 20 Gy)
      and time-dependent (6-72 h) manner. The total expression levels of eNOS were
      unchanged by radiation. Although a transient but significant increase in
      extracellular signal-regulated protein kinase 1/2 (ERK1/2) phosphorylation and a
      biphasic decline in Akt phosphorylation were observed after irradiation, these
      inhibitors were without effect on the radiation-induced changes in eNOS
      phosphorylation. There was an increase in protein kinase C-betaII (PKC-betaII)
      expression and the ablation of PKC-betaII by small interfering RNA (siRNA)
      negated the radiation effect on the two eNOS phosphorylation events. Furthermore,
      when the radiation-induced increase in reactive oxygen species (ROS) generation
      was prevented by the anti-oxidant N-acetyl-L-cysteine, eNOS Ser-1177
      phosphorylation and Thr-495 dephosphorylation in irradiated HUVECs were
      significantly reduced. However, transfection of PKC-beta siRNA did not alter ROS
      production after irradiation, and NAC failed to block the radiation-induced
      increase in PKC-betaII expression. Taken together, our results suggest that
      ionizing radiation-induced eNOS activation in human vascular endothelial cells is
      attributed to both the up-regulation of PKC-betaII and the increase in ROS
      generation which were independent of each other.

PMID- 25869504
TI  - Participation of the TRP channel in the cardiovascular effects induced by
      carvacrol in normotensive rat.
AB  - Carvacrol has been described as an agonist/antagonist of different transient
      receptor potential (TRP) channels and voltage-dependent calcium channels (Cavs).
      The aim of this study was to evaluate the role of Cav and TRP channels following
      carvacrol stimulation. Initially, in mesenteric artery rings carvacrol relaxed
      phenylephrine-induced contractions. Furthermore, carvacrol inhibited contraction
      elicited by CaCl2 in depolarizing nominally without Ca2+ medium and antagonized
      the contractions induced by S(-)-Bay K 8644 and inhibited Ca2+ currents
      indicating the inhibition of Ca2+ influx through L-type Cav. Additionally,
      carvacrol antagonized the contractions induced by CaCl2 in the presence of
      nifedipine/Cyclopiazonic acid/phenylephrine or nifedipine/Cyclopiazonic acid/KCl
      60, suggesting a possible inhibition of calcium influx by store operated channels
      (SOCs), receptor operated channels (ROCs) and/or TRP channels. Interestingly,
      among the TRP channel blockers used, the effect induced by carvacrol was
      attenuated by Mg2+ and potentiated by La3+ and Gd3+, suggesting that TRP channels
      are involved in relaxation induced by carvacrol. Monoterpene also induced
      hypotension and bradycardia in non-anesthetized normotensive rats and negative
      inotropic and chronotropic effects. In conclusion, these results suggest that the
      hypotensive effect of carvacrol is probably due to bradycardia and a peripheral
      vasodilatation that involves, at least, the inhibition of the Ca2+ influx through
      Cav and TRP channels.

PMID- 25869505
TI  - Infliximab improves endothelial dysfunction in a mouse model of antiphospholipid
      syndrome: Role of reduced oxidative stress.
AB  - Antiphospholipid syndrome (APS), induces endothelial dysfunction, oxidative
      stress and systemic inflammation that may be mediated by TNFalpha. Thus, we
      investigated the possible protective effect of the anti-TNFalpha antibody
      infliximab (5MUg/g) on endothelial function in a mouse APS model (induced by
      injection of purified human anti-beta2GP1-IgG). Seven days after anti-beta2GPI
      IgG injection, we observed an increase in plasma sVCAM-1 and sE-selectin levels
      and in aortic mRNA expression of VCAM-1 and E-selectin. This was associated with
      a decreased endothelium-dependent relaxation of isolated mesenteric arteries to
      acetylcholine, together with decreased mesenteric eNOS mRNA expression and
      increased eNOS uncoupling, accompanied by increased iNOS and gp91phox mRNA and
      increased left ventricular GSH/GSSH ratio. Infliximab significantly improved the
      NO-mediated relaxing responses to acetylcholine, and induced a decrease in iNOS
      and gp91phox mRNA expression. The opro-adhesive and pro-coagulant phenotypes
      induced by the anti-beta2GP1-IgG were also reversed. This study provides the
      first evidence that TNFalpha antagonism improves endothelial dysfunction in APS
      and suggests that endothelial dysfunction is mediated by TNFalpha and oxidative
      stress. Therefore, infliximab may be of special relevance in clinical practice. 

PMID- 25869506
TI  - Treatment with sulphated galactan inhibits macrophage chemotaxis and reduces
      intraplaque macrophage content in atherosclerotic mice.
AB  - Experimental data from animal models and clinical studies support connections
      between the haemostasis and inflammation in atherogenesis. These interfaces among
      inflammation and thrombogenesis have been suggested as targets for
      pharmacological intervention to reduce disease progression. We hypothesize that
      the recently discovered antithrombotic drug Sulphated Galactan (SG) (isolated
      from the red marine alga Acanthophora muscoides) might reduce atherosclerotic
      plaque vulnerability and inflammatory gene expression in 10-week aged
      apolipoprotein E deficient (ApoE-/-) mice under high-cholesterol diet for
      additional 11weeks. Then, the underlying cellular mechanisms were investigated in
      vitro. SG (10mg/kg) or Vehicle was subcutaneously injected from week 6 until week
      11 of the diet. Treatment with SG reduced intraplaque macrophage and Tissue
      Factor (TF) content as compared to Vehicle-treated animals. Intraplaque TF co
      localized and positively correlated with macrophage rich-areas. No changes on
      atherosclerotic plaque size, and other intraplaque features of vulnerability
      (such as lipid, neutrophil, MMP-9 and collagen contents) were observed. Moreover,
      mRNA expression of MMPs, chemokines and genetic markers of Th1/2/reg/17
      lymphocyte polarization within mouse aortic arches and spleens was not affected
      by SG treatment. In vitro, treatment with SG dose-dependently reduced macrophage
      chemotaxis without affecting TF production. Overall, the chronic SG treatment was
      well tolerated. In conclusion, our results indicate that SG treatment reduced
      intraplaque macrophage content (by impacting on cell recruitment) and,
      concomitantly, intraplaque TF content of potential macrophage origin in
      atherosclerotic mice. 

PMID- 25869507
TI  - Combined treatment with atorvastatin and imipenem improves survival and vascular
      functions in mouse model of sepsis.
AB  - We have recently reported that pre-treatment, but not the post-treatment with
      atorvastatin showed survival benefit and improved hemodynamic functions in cecal
      ligation and puncture (CLP) model of sepsis in mice. Here we examined whether
      combined treatment with atorvastatin and imipenem after onset of sepsis can
      prolong survival and improve vascular functions. At 6 and 18h after sepsis
      induction, treatment with atorvastatin plus imipenem, atorvastatin or imipenem
      alone or placebo was initiated. Ex vivo experiments were done on mouse aorta to
      examine the vascular reactivity to nor-adrenaline and acetylcholine and mRNA
      expressions of alpha1D AR, GRK2 and eNOS. Atorvastatin plus imipenem extended the
      survival time to 56.00+/-4.62h from 20.00+/-1.66h observed in CLP mice. The
      survival time with atorvastatin or imipenem alone was 20.50+/-1.89h and 27.00+/
      4.09h, respectively. The combined treatment reversed the hyporeactivity to nor
      adrenaline through preservation of alpha1D AR mRNA/protein expression and
      reversal of alpha1D AR desensitization mediated by GRK2/Gbetagamma pathway. The
      treatment also restored endothelium-dependent relaxation to ACh through
      restoration of aortic eNOS mRNA expression and NO availability. In conclusion,
      combined treatment with atorvastatin and imipenem exhibited survival benefit and
      improved vascular functions in septic mice. 

PMID- 25869508
TI  - Des-aspartate angiotensin I (DAA-I) reduces endothelial dysfunction in the aorta
      of the spontaneously hypertensive rat through inhibition of angiotensin II
      induced oxidative stress.
AB  - Des-aspartate angiotensin I (DAA-I), an endogenous nonapeptide, counteracts
      several effects of angiotensin II on vascular tone. The aim of this study was to
      investigate the acute protective effect of DAA-I on endothelial function in the
      spontaneously hypertensive rat (SHR) as well as its effect on angiotensin II
      induced contractions and oxidative stress. Aortic rings were incubated with DAA-I
      (0.1MUM) for 30min prior to the assessment of angiotensin II-induced contractions
      (0.1nM-10MUM) in WKY and SHR aortas. Total nitrate and nitrite levels were
      assessed using a colorimetric method and reactive oxygen species (ROS) were
      measured by dihydroethidium (DHE) fluorescence and lucigenin-enhanced
      chemiluminescence. The effect of DAA-I was also assessed against endothelium
      dependent and -independent relaxations to acetylcholine and sodium nitroprusside,
      respectively. Angiotensin II-induced contractions were significantly reduced by
      DAA-I, losartan and tempol. Incubation with ODQ (soluble guanylyl cyclase
      inhibitor) and removal of the endothelium prevented the reduction of angiotensin
      II-induced contractions by DAA-I. Total nitrate and nitrite levels were increased
      in DAA-I, losartan and tempol treated-SHR tissues while ROS level was reduced by
      DAA-I and the latter inhibitors. In addition, DAA-I significantly improved the
      impaired acetylcholine-induced relaxation in SHR aortas whilst sodium
      nitroprusside-induced endothelium-independent relaxation remained unaffected. The
      present findings indicate that improvement of endothelial function by DAA-I in
      the SHR aorta is mediated through endothelium-dependent release of nitric oxide
      and inhibition of angiotensin II-induced oxidative stress. 

PMID- 25869509
TI  - Effects of high flavanol dark chocolate on cardiovascular function and platelet
      aggregation.
AB  - Regular consumption of chocolate and cocoa products has been linked to reduced
      cardiovascular mortality. This study compared the effects of high flavanol dark
      chocolate (HFDC; 1064mg flavanols/day for 6weeks) and low flavanol dark chocolate
      (LFDC; 88mg flavanols/day for 6weeks) on blood pressure, heart rate, vascular
      function and platelet aggregation in men with pre-hypertension or mild
      hypertension. Vascular function was assessed by pulse wave analysis using radial
      artery applanation tonometry in combination with inhaled salbutamol (0.4mg) to
      assess changes due to endothelium-dependent vasodilatation. HFDC did not
      significantly reduce blood pressure compared to baseline or LFDC. Heart rate was
      increased by LFDC compared to baseline, but not by HFDC. Vascular responses to
      salbutamol tended to be greater after HFDC. Platelet aggregation induced by
      collagen or the thromboxane analogue U46619 was unchanged after LFDC or HFDC,
      whereas both chocolates reduced responses to ADP and the thrombin receptor
      activator peptide, SFLLRNamide (TRAP6), relative to baseline. Pre-incubation of
      platelets with theobromine also attenuated platelet aggregation induced by ADP or
      TRAP6. We conclude that consumption of HFDC confers modest improvements in
      cardiovascular function. Platelet aggregation is modulated by a flavanol
      independent mechanism that is likely due to theobromine. 

PMID- 25869510
TI  - Optogenetic approach for functional assays of the cardiovascular system by light
      activation of the vascular smooth muscle.
AB  - Cardiovascular diseases are the major challenge to modern medicine. Intervention
      to cardiovascular cells is crucial for treatment of the diseases. Here we report
      a novel intervention to vascular smooth muscle (VSM) cells by optogenetics.
      Channelrhodopsin in a tandem with YFP was selectively expressed in smooth muscle
      of transgenic mice in which YFP fluorescence was found in arterial walls of
      various tissues. In dissociated VSM cells from the mice blue light evoked inward
      currents, leading to depolarization and contraction. In isolated mesenteric
      arterial rings, optostimulation produced vasoconstriction that was reproducible,
      sustained, light intensity-dependent and comparable to popular vasoconstrictors.
      Blue light raised robustly coronary resistance without significant effects on
      heart rate and pulse pressure. Optostimulation produced renal vasoconstriction as
      well. The optical vasoconstriction had temporal resolutions less than 40s in
      these organs. These results indicate that optical vasoconstriction can be
      effectively produced in various organs with channelrhodopsin expression in VSM
      cells. 

PMID- 25869511
TI  - Cyclooxygenase inhibition and rosuvastatin-induced vascular protection in the
      setting of ischemia-reperfusion: A human in vivo study.
AB  - The 3-hydroxy-3-methylglutaryl coenzyme A (HMG Co-A) reductase inhibitors have
      preconditioning effects involving up-regulation of cyclooxygenase (COX)-2. We
      investigated the effect of selective and non-selective COX inhibition on
      rosuvastatin-mediated protection against ischemia-reperfusion (IR)-induced
      endothelial dysfunction in the human forearm. Healthy volunteers (n=66) were
      allocated to placebo, acetylsalicylic acid (ASA) 81mg daily, ASA 325mg daily,
      celecoxib 200mg twice daily or 400mg ibuprofen four times daily, each
      administered for 5 to 7days. On the last day of study drug therapy, subjects
      received a single dose of 40mg rosuvastatin. Twenty-four hours later flow
      mediated dilation (FMD) of the radial artery was evaluated before and after IR.
      In the placebo group, FMD was similar before and after IR (8.1+/-1.0 vs 7.2+/
      0.8%; P=NS) indicating a significant protective effect of rosuvastatin. There was
      also no effect of IR on FMD in the ASA 81mg group (6.7+/-0.6 vs 6.1+/-0.7%;
      P=NS). In contrast, following IR there was a significant decrease in FMD in the
      ASA 325mg group (7.2+/-0.8 vs 3.3+/-0.7%, P<0.001), the celecoxib group (7.3+/
      1.5 vs 2.6+/-1.5%, P<0.01) as well as the ibuprofen group (6.8+/-0.7 vs 2.6+/
      0.8%; P<0.01). Therefore, nonselective COX inhibition with ASA 325mg and
      ibuprofen completely inhibit the protective effects of rosuvastatin in the
      setting of IR injury, as does therapy with the specific COX-2 antagonist
      celecoxib. In contrast, therapy with low dose ASA (81mg daily) does not have such
      inhibitory effects. 

PMID- 25869512
TI  - 17beta-estradiol potentiates endothelium-dependent nitric oxide- and
      hyperpolarization-mediated relaxations in blood vessels of male but not female
      apolipoprotein-E deficient mice.
AB  - The present study investigated the influence of gender on the changes underlying
      endothelial dysfunction in hyperlipidemia during aging. Isometric tension in
      rings (with endothelium) of the aortae and superior mesenteric arteries from
      apolipoprotein-E deficient mice was determined in wire myographs. Nitric oxide
      (NO)- and endothelium-dependent hyperpolarization (EDH)-mediated relaxations were
      smaller in the aortae and mesenteric arteries of 32weeks old males than eight
      weeks old males. In females, NO- and EDH-mediated relaxations were impaired only
      at 84weeks of age. The levels of reactive oxygen species were elevated in the
      blood vessels of 32weeks old males, but not females. Acute in vitro treatment
      with 17beta-estradiol and apocynin improved NO- and EDH-mediated relaxations in
      32weeks old males but not in 84weeks old males. Relaxations to SKA-31, activator
      of intermediate (IKCa) and small (SKCa) conductance calcium-activated potassium
      channels, were attenuated in the mesenteric arteries of 32weeks old males. Such
      impairment was restored by acute treatment with apocynin. These findings suggest
      that male hyperlipidemic mice develop endothelial dysfunction at an earlier age
      than females. This endothelial dysfunction is associated with impaired NO
      bioavailability and reduced IKCa and SKCa activity. Apocynin and 17beta-estradiol
      restore the endothelial function only in younger male animals but not in older
      male or female animals. 

PMID- 25869513
TI  - Gender specific generation of nitroxyl (HNO) from rat endothelium.
AB  - Nitric oxide (NO) has long been accepted as the majority biological mediator
      underlying the critically important vasodilator function of the vascular
      endothelium yet there is growing evidence that the protonated one-electron
      reduction species of NO, nitroxyl (HNO), may also have biological activity. In
      this study we examined if there was a gender variation in the production of HNO
      from the endothelium of isolated segments of rat aorta. By use of recognized
      pharmacological inhibitors, we found that when the endothelium was stimulated by
      acetylcholine vascular relaxation was mediated entirely via NO in tissue from
      both males and females. The vasorelaxation induced by basal (non-stimulated)
      endothelium from females was also mediated entirely by NO. However, in contrast,
      the influence of basally active endothelium in males was mediated by both NO and
      HNO. The generation of HNO in males was dependent on endothelial nitric oxide
      synthase and relaxation was mediated via activation of soluble guanylate cyclase.
      We believe that this is the first evidence of a gender variation in the
      production of HNO and this may have important implications for our understanding
      of disparity in the development of cardiovascular disease between the sexes. 

PMID- 25869514
TI  - The innate immune system, toll-like receptors and dermal wound healing: A review.
AB  - Wound healing is a complex physiological process comprised of discrete but inter
      related and overlapping stages, requiring exact timing and regulation to
      successfully progress, yet occurs spontaneously in response to injury. It is
      characterised by four phases, coagulation, inflammation, proliferation and
      remodelling. Each phase is predominated by particular cell types, cytokines and
      chemokines. The innate immune system represents the first line of defence against
      invading microorganisms. It is entirely encoded with the genome, and comprised of
      a cellular response with specificity provided by pattern recognition receptors
      (PRRs) such as toll-like receptors (TLRs). TLRs are activated by exogenous
      microbial pathogen associated molecular patterns (PAMPs), initiating an immune
      response through the production of pro-inflammatory cytokines and further
      specialist immune cell recruitment. TLRs are also activated by endogenous
      molecular patterns termed damage associated molecular patterns (DAMPs). These
      ligands, usually shielded from the immune system, act as alarm signals alerting
      the immune system to damage and facilitate the normal wound healing process. TLRs
      are expressed by cells essential to wound healing such as keratinocytes and
      fibroblasts, however the specific role of TLRs in this process remains
      controversial. This article reviews the current knowledge on the potential role
      of TLRs in dermal wound healing where inflammation arising from pathogenic
      activation of these receptors appears to play a role in chronic ulceration
      associated with diabetes, scar hypertrophy and skin fibrosis. 

PMID- 25869515
TI  - Ticagrelor potentiates adenosine-induced stimulation of neutrophil chemotaxis and
      phagocytosis.
AB  - In the PLATO study, ticagrelor was associated with fewer pulmonary infections and
      subsequent deaths than clopidogrel. Neutrophils are a first-line defence against
      bacterial lung infection; ticagrelor inhibits cellular uptake of adenosine, a
      known regulator of neutrophil chemotaxis and phagocytosis. We assessed whether
      the inhibition of adenosine uptake by ticagrelor influences neutrophil chemotaxis
      and phagocytosis. Neutrophils and erythrocytes were isolated from healthy
      volunteers. Concentration-dependent effects of adenosine on IL-8-induced
      neutrophil chemotaxis were investigated and the involved receptors identified
      using adenosine receptor antagonists. The modulatory effects of ticagrelor on
      adenosine-mediated changes in neutrophil chemotaxis and phagocytosis of
      Streptococcus pneumoniae were determined in the presence of erythrocytes to
      replicate physiological conditions of cellular adenosine uptake. Low
      concentration adenosine (10(-8)M) significantly increased IL-8-induced neutrophil
      chemotaxis (% neutrophil chemotaxis: adenosine 28.7%+/-4.4 vs. control 22.6%+/
      2.4; p<0.01) by acting on the high-affinity A1 receptor. Erythrocytes attenuated
      the effect of adenosine, although this was preserved by ticagrelor and
      dipyridamole (another inhibitor of adenosine uptake) but not by control or by
      cangrelor. Similarly, in the presence of erythrocytes, a low concentration of
      adenosine (10(-8)M) significantly increased neutrophil phagocytic index compared
      to control when ticagrelor was present (37.6+/-6.6 vs. 28.0+/-6.6; p=0.028) but
      had no effect in the absence of ticagrelor. We therefore conclude that the
      inhibition of cellular adenosine reuptake by ticagrelor potentiates the effects
      of a nanomolar concentration of adenosine on neutrophil chemotaxis and
      phagocytosis. This represents a potential mechanism by which ticagrelor could
      influence host defence against bacterial lung infection. 

PMID- 25869516
TI  - The role of oxidative stress, antioxidants and vascular inflammation in
      cardiovascular disease (a review).
AB  - The concept of mild chronic vascular inflammation as part of the pathophysiology
      of cardiovascular disease, most importantly hypertension and atherosclerosis, has
      been well accepted. Indeed there are links between vascular inflammation,
      endothelial dysfunction and oxidative stress. However, there are still gaps in
      our understanding regarding this matter that might be the cause behind
      disappointing results of antioxidant therapy for cardiovascular risk factors in
      large-scale long-term randomised controlled trials. Apart from the limitations of
      our knowledge, limitations in methodology and assessment of the body's endogenous
      and exogenous oxidant-antioxidant status are a serious handicap. The pleiotropic
      effects of antioxidant and anti-inflammation that are shown by some well
      established antihypertensive agents and statins partly support the idea of using
      antioxidants in vascular diseases as still relevant. This review aims to provide
      an overview of the links between oxidative stress, vascular inflammation,
      endothelial dysfunction and cardiovascular risk factors, importantly focusing on
      blood pressure regulation and atherosclerosis. In view of the potential benefits
      of antioxidants, this review will also examine the proposed role of vitamin C,
      vitamin E and polyphenols in cardiovascular diseases as well as the success or
      failure of antioxidant therapy for cardiovascular diseases in clinical trials. 

PMID- 25869517
TI  - Combination of spices and herbal extract restores macrophage foam cell migration
      and abrogates the athero-inflammatory signalling cascade of atherogenesis.
AB  - The trapping of lipid-laden macrophages in the arterial intima is a critical but
      reversible step in atherogenesis. However, information about possible treatments
      for this condition is lacking. Here, we hypothesized that combining the
      polyphenol-rich fractions (PHC) of commonly consumed spices (Allium sativum L
      (Liliaceae), Zingiber officinale R (Zingiberaceae), Curcuma longa L
      (Zingiberaceae)) and herbs (Terminalia arjuna (R) W & A (Combretaceae) and
      Cyperus rotundus L (Cyperaceae)) prevents foam cell formation and atherogenesis.
      Using an in vitro foam cell formation assay, we found that PHC significantly
      inhibited lipid-laden macrophage foam cell formation compared to the depleted
      polyphenol fraction of PHC (F-PHC). We further observed that PHC attenuated the
      LDL and LPS induced CD36, p-FAK and PPAR-gamma protein expression in macrophages
      and increased their migration. NK-kappaB-DNA interaction, TNF-alpha, ROS
      generation, and MMP9 and MMP2 protein expression were suppressed in PHC-treated
      macrophages. The anti-atherosclerotic activity of PHC was investigated in a high
      fat- and cholesterol-fed rabbit model. The inhibition of foam cell deposition
      within the aortic intima and atheroma formation confirmed the atheroprotective
      activity of PHC. Therefore, we conclude that the armoury of polyphenols in PHC
      attenuates the CD36 signalling cascade-mediated foam cell formation, enhances the
      migration of these cells and prevents atherogenesis. 

PMID- 25869518
TI  - Propylthiouracil modulates aortic vasculopathy in the oxidative stress model of
      systemic sclerosis.
AB  - BACKGROUND: In systemic sclerosis (SSc) vasculopathy affects small arteries and
      capillaries, but recent evidences show also macrovascular alterations.
      Experimental data suggest that propylthiouracil (PTU) abrogates the development
      of cutaneous and pulmonary fibrosis during SSc. The aim of this study was to
      evaluate the effect of propylthiouracil on aortic lipid peroxidation, intima
      media thickness and myofibroblasts differentiation in experimental SSc. METHODS:
      SSc was induced in BALB/c mice by daily subcutaneous injections of hypochlorous
      acid (HOCl) for 6weeks. Mice (n=25) were randomized to receive daily: HOCl
      (n=10), HOCl+PTU (n=10), or vehicle (n=5). Thoracic aorta was evaluated by
      histological methods to measure intima-media thickness and by immunostaining for
      alpha-smooth muscle actin (alpha-SMA) to assess myofibroblast differentiation.
      Aortic and plasma levels of malondialdehyde (MDA) were also measured. RESULTS:
      HOCl induced a significant increase in aortic intima-media thickness compared to
      controls (p<0.001), while PTU administration prevented intima-media thickening
      (p<0.01). Myofibroblast differentiation was also less evident in HOCl+PTU-treated
      animals (p<0.05) compared to mice treated with HOCl alone. The increase in aortic
      and plasma MDA levels induced by HOCl, was significantly prevented by PTU
      administration (p<0.05). CONCLUSION: PTU, by reducing lipid peroxidation,
      prevents aortic thickening and myofibroblast differentiation induced by HOCl,
      reducing macrovascular alterations in experimental SSc.

PMID- 25869519
TI  - New indole-thiazolidine attenuates atherosclerosis in LDLr(-/-) mice.
AB  - Thiazolidinediones (TZDs) are peroxisome proliferator-activated receptor gamma
      (PPARgamma) agonists that improve insulin-mediated glucose uptake and possess
      beneficial vasculoprotective actions. However, because undesirable side effects
      are associated with these drugs, novel TZDs are under development. In this study,
      we evaluated the biological activity of LYSO-7, a new indole-thiazolidine, on
      PPAR activation, inflammation and atherogenesis using a gene reporter assay,
      lipopolysaccharide (LPS)-activated RAW 264.7 cell culture, and a low-density
      lipoprotein receptor knockout (LDLr(-/-)) mouse model of atherosclerosis. LYSO-7
      shows low cytotoxicity in RAW 264.7 cells and at 2.5MUmol/L induces PPARalpha and
      PPARgamma transactivation as well as inhibits LPS-induced nitrite production and
      the mRNA gene expression levels of inducible nitric oxide synthase (iNOS),
      cyclooxygenase-2 (COX-2), vascular cell adhesion molecule-1 (VCAM-1) and monocyte
      chemoattractant protein-1 (MCP-1). In addition, treatment with LYSO-7 reduces the
      development of atherosclerosis in LDLr(-/-) mice, improves the lipid profile,
      blood glucose levels, and downregulates CD40 and CD40L expression without
      affecting the body weight of the animals. Altogether, our data show that LYSO-7
      possesses anti-inflammatory properties and that treatment with this TZD
      attenuates atherosclerosis progression in LDLr(-/-) mice by modulating lipid
      metabolism and inflammation. Thus, LYSO-7 shows potential as a new drug candidate
      for the treatment of atherosclerosis. 

PMID- 25869520
TI  - Circulating endothelial progenitor cells: Do they live up to their name?
AB  - Preclinical and clinical studies have suggested that specific subsets of cells
      isolated from the bone marrow or peripheral blood, collectively named endothelial
      progenitor cells (EPCs), play an essential role in neovascularization and are
      biomarkers of atherosclerosis, inversely related to the presence and progression
      of the disease. Conclusive evidence for both the pathophysiological and the
      biomarker role of these cells is, however, missing, with lack of a unique and
      universally accepted interpretation for their role, and the absence of general
      agreement to prompt their use by the practicing clinician. In fact, the
      engraftment of EPCs after injection into ischemic areas is poor, their secretome
      is still largely unknown, and there are still many confounding factors-such as co
      morbidities and medications-that limit their use as a faithful biomarker of
      disease. Here we briefly review the literature on EPCs and discuss their
      significance in cardiovascular disease both as mediators and as biomarkers,
      including current methods for their identification. 

PMID- 25869522
TI  - Effect of soluble guanylyl cyclase activator and stimulator therapy on
      nitroglycerin-induced nitrate tolerance in rats.
AB  - Chronic nitroglycerin (GTN) anti-ischemic therapy induces side effects such as
      nitrate tolerance and endothelial dysfunction. Both phenomena could be based on a
      desensitization/oxidation of the soluble guanylyl cyclase (sGC). Therefore, the
      present study aims at investigating the effects of the therapy with the sGC
      activator BAY 60-2770 and the sGC stimulator BAY 41-8543 on side effects induced
      by chronic nitroglycerin treatment. Male Wistar rats were treated with
      nitroglycerin (100mg/kg/d for 3.5days, s.c. in ethanol) and BAY 60-2770 (0.5 or
      2.5mg/kg/d) or BAY 41-8543 (1 and 5mg/kg/d) for 6days. Therapy with BAY 60-2770
      but not with BAY 41-8543 improved nitroglycerin-triggered endothelial dysfunction
      and nitrate tolerance, corrected the decrease in aortic nitric oxide levels,
      improved the cGMP dependent activation of protein kinase I in aortic tissue and
      reduced vascular, cardiac and whole blood oxidative stress (fluorescence and
      chemiluminescence assays; 3-nitrotyrosine staining). In contrast to BAY 41-8543,
      the vasodilator potency of BAY 60-2770 was not impaired in isolated aortic ring
      segments from nitrate tolerant rats. sGC activator therapy improves partially the
      adverse effects of nitroglycerin therapy whereas sGC stimulation has only minor
      beneficial effects pointing to a nitroglycerin-dependent sGC
      oxidation/inactivation mechanism contributing to nitrate tolerance. 

PMID- 25869521
TI  - ROCK2 primes the endothelium for vascular hyperpermeability responses by raising
      baseline junctional tension.
AB  - Rho kinase mediates the effects of inflammatory permeability factors by
      increasing actomyosin-generated traction forces on endothelial adherens
      junctions, resulting in disassembly of intercellular junctions and increased
      vascular leakage. In vitro, this is accompanied by the Rho kinase-driven
      formation of prominent radial F-actin fibers, but the in vivo relevance of those
      F-actin fibers has been debated, suggesting other Rho kinase-mediated events to
      occur in vascular leak. Here, we delineated the contributions of the highly
      homologous isoforms of Rho kinase (ROCK1 and ROCK2) to vascular hyperpermeability
      responses. We show that ROCK2, rather than ROCK1 is the critical Rho kinase for
      regulation of thrombin receptor-mediated vascular permeability. Novel traction
      force mapping in endothelial monolayers, however, shows that ROCK2 is not
      required for the thrombin-induced force enhancements. Rather, ROCK2 is pivotal to
      baseline junctional tension as a novel mechanism by which Rho kinase primes the
      endothelium for hyperpermeability responses, independent from subsequent ROCK1
      mediated contractile stress-fiber formation during the late phase of the
      permeability response. 

PMID- 25869523
TI  - HIF-regulated HO-1 gene transfer improves the post-ischemic limb recovery and
      diminishes TLR-triggered immune responses - Effects modified by concomitant VEGF
      overexpression.
AB  - Heme oxygenase-1 (HO-1) mitigates cellular injury by antioxidant, anti-apoptotic,
      anti-inflammatory and proangiogenic effects. Vascular endothelial growth factor
      (VEGF) is a critical regulator of blood vessel growth. Their coordinated action
      was analyzed in a model of femoral artery ligation (FAL) in mice lacking HO-1
      gene (HO-1 KO). Gastrocnemius skeletal muscles of HO-1 KO mice were preemptively
      injected with plasmids containing hypoxia-response element (HRE) driving the
      expression of only HO-1 (pHRE-HO1) or both HO-1 and VEGF (pHRE-HO1-VEGF). At day
      14th the pHRE-HO1 vector increased an impaired post-ischemic blood flow recovery
      in HO-1 KO mice to the level observed in wild-type (WT) mice subjected to FAL and
      pHRE-HO1-VEGF restored it already at day 7. The pHRE-HO1 gene therapy diminished,
      when compared to control pHRE-empty-treated HO-1 KO mice, the expression of toll
      like receptors (TLR4 and TLR9) and inflammatory cytokines (IL-1beta, IL-6 and
      TNFalpha) at day 3, whereas opposite effects were observed following concomitant
      HO-1 and VEGF gene transfer. Moreover, HO-1 diminished ischemia-induced
      expression of MyoD involved in satellite cell differentiation in HO-1 KO mice.
      Our results confirm the therapeutic potential of HO-1 and VEGF against critical
      limb ischemia although, their concomitant delivery may have contradictory actions
      on the resolution of inflammation. 

PMID- 25869524
TI  - Dual Sensory Impairment and Cognitive Decline: The Results From the Shelter
      Study.
AB  - OBJECTIVES: To examine whether nursing home residents with concurrent vision and
      hearing impairment, dual sensory impairment (DSI), have a greater cognitive
      decline over time than do those without sensory impairment and whether social
      engagement modifies this association. METHODS: Based on the Services and Health
      for Elderly in Long TERm Care study, 1,989 nursing home residents who were
      assessed using the interRAI LTCF at 6-month intervals over 1 year were included.
      Multivariate linear regression models with time-variant exposure variables of
      sensory impairment and social engagement using generalized estimating equations
      were performed to predict cognitive function measured by the Cognitive
      Performance Scale (range 0-6). RESULTS: Residents with DSI had a greater
      cognitive decline [changes in Cognitive Performance Scale over 1 year = 1.12 (95%
      confidence interval = 0.81:1.42)] compared to those with either vision or hearing
      impairment [0.67 (0.53:0.64)] and those without sensory impairment [0.56
      (0.48:0.64)]. A lower level of social engagement was also associated with a
      greater cognitive decline. The combined exposure variable of sensory impairment
      and social engagement revealed the greatest cognitive decline for socially
      disengaged residents with DSI [1.87 (1.24:2.51)] and the potential effect
      modification of social engagement on the association between DSI and cognitive
      decline; DSI was not associated with a greater cognitive decline among socially
      engaged residents, while it was associated among socially disengaged residents
      DISCUSSION: Cognitive function declines faster in nursing home residents with DSI
      only when residents were not socially engaged. Therefore, residents with DSI
      might cognitively benefit from interventions to improve involvement in social
      life at nursing homes.

PMID- 25869525
TI  - Living Alone and Patient Care Experiences: The Role of Gender in a National
      Sample of Medicare Beneficiaries.
AB  - BACKGROUND: Seniors who live alone are a large, growing population with poorer
      health outcomes. We examine the little-studied health care experiences and
      immunizations of older adults who live alone. METHODS: We use regression-based
      case-mix adjustment to compare immunizations and health care experiences of
      325,649 adults aged 65 and older who lived alone to those who did not, overall
      and by gender and health status, using nationally representative data from the
      Medicare Consumer Assessment of Healthcare Providers and Systems (MCAHPS)
      surveys. Outcomes were five global care ratings (health plan, drug plan, doctor,
      specialists, all care), six composite care measures (getting needed care, getting
      care quickly, doctor communication, customer service, getting needed drugs,
      getting information from drug plan), and two immunization measures (influenza,
      pneumonia). RESULTS: About 30.3% of respondents lived alone. Women, older
      beneficiaries, and low income (Medicaid eligible) beneficiaries reported living
      alone at substantially higher rates than their counterparts. Care experiences for
      8 of the 13 measures were significantly worse for those who lived alone than for
      others. The association differed significantly in magnitude by gender for 10
      measures, with larger average differences for men. The largest disadvantages for
      those living alone were for immunization measures (eg, influenza -6 percentage
      points, for men living alone vs other men). The disadvantages of living alone
      were not consistently greater for those in worse health. CONCLUSIONS: Living
      alone is associated with worse care experiences and immunization, especially for
      men. Health plans should target quality improvement and outreach efforts to
      beneficiaries who live alone, especially men.

PMID- 25869526
TI  - Effect of lung transplantation on heart rate response to exercise.
AB  - OBJECTIVES: To evaluate if patients have a change in percent of predicted heart
      rate reserve used at peak exercise (%HRR) after lung transplantation, even at
      matching workloads. BACKGROUND: Lung disease of obstructive, restrictive, and
      mixed types may be associated with an autonomic imbalance. Lung transplantation
      may improve the effects of pulmonary disease on cardiac function. However, the
      effect of lung transplantation on heart rate responses during exercise has not
      been investigated in detail. METHODS: Retrospective review of patients who
      underwent lung transplantation. Pre and post transplant cardiopulmonary exercise
      tests were reviewed. RESULTS: The %HRR significantly improved by a median of 37%
      (p < 0.001) following lung transplantation. When matching workloads were
      analyzed, the %HRR also decreased from a median of 36% to 24% (p < 0.001).
      CONCLUSIONS: Corresponding to an increase in peak exercise capacity, percentage
      of heart rate reserve used improves significantly after lung transplantation,
      even at matching workloads, indicating a likely improvement in autonomic
      modulation.

PMID- 25869528
TI  - Rational synthesis of novel recyclable Fe3O4@MOF nanocomposites for enzymatic
      digestion.
AB  - In this work, for the first time, magnetic MOFs were synthesized as carriers for
      enzyme immobilization. The magnetic MOF-enzyme composites exhibited significantly
      improved digestion performance, excellent reusability, stability and
      reproducibility for different kinds of enzymes. 

PMID- 25869530
TI  - BRCA2 variant aerodigestive cancer risk.

PMID- 25869529
TI  - Lamellar pathology in horses with pituitary pars intermedia dysfunction.
AB  - REASONS FOR PERFORMING STUDY: Hoof lamellar pathology in horses with pituitary
      pars intermedia dysfunction (PPID) has not been described previously. OBJECTIVES:
      To describe the histomorphometry and pathological lesions in hoof lamellar tissue
      of animals that had PPID with or without concurrent laminitis, with reference to
      age-matched controls. We hypothesised that lamellar lesions consistent with
      laminitis would be associated with PPID, even in animals without current or
      historical laminitis. STUDY DESIGN: Prospective case-control study. METHODS: Mid
      dorsal hoof histological sections were obtained post mortem from the forelimbs of
      16 PPID-affected animals either with (n = 6) or without laminitis (n = 10) and 10
      age- and breed-matched controls. Sections were examined by a blinded veterinary
      pathologist. The length and width of 10 primary epidermal lamellae were measured
      using image analysis software. The morphology and pathology of primary and
      secondary epidermal lamellae were then typed or graded in axial, middle and
      abaxial regions. Fasting serum insulin, plasma adrenocorticotropin and blood
      glucose concentration were measured from blood samples taken prior to euthanasia.
      RESULTS: All animals with PPID and laminitis had fasting hyperinsulinaemia
      (median 74.1 miu/l, interquartile range 49.9-349.5 miu/l) whereas PPID animals
      without laminitis had serum insulin concentrations below the upper limit of the
      reference range (<20 miu/l). Lamellar pathology in PPID animals with laminitis
      was variable in severity and unrelated to the reported duration of laminitis
      (range 2 months-5 years). Most lesions were located abaxially within the lamellar
      tissue and included increased length and width of the lamellae, chronic abnormal
      keratinisation, interlamellar epidermal bridging and cell death with more acute
      lamellar tearing in some cases. The lamellae of PPID animals without laminitis
      were normal referent to the relevant control group. CONCLUSIONS: Whether PPID and
      hyperinsulinaemia have a causal inter-relationship or not, it may only be the
      hyperinsulinaemia that is associated with lamellar morphological alteration and
      pathology consistent with laminitis.

PMID- 25869527
TI  - Looking beyond the induction of Th2 responses to explain immunomodulation by
      helminths.
AB  - Although helminth infections are characteristically associated with Th2-mediated
      responses that include the production of the prototypical cytokines IL-4, IL-5
      and IL-13 by CD4(+) cells, the production of IgE, peripheral blood eosinophilia
      and mucus production in localized sites, these responses are largely attenuated
      when helminth infections become less acute. This modulation of the immune
      response that occurs with chronic helminth infection is often induced by
      molecules secreted by helminth parasites, by non-Th2 regulatory CD4(+) cells, and
      by nonclassical B cells, macrophages and dendritic cells. This review will focus
      on those parasite- and host-mediated mechanisms underlying the modulated T-cell
      response that occurs as the default in chronic helminth infections. 

PMID- 25869531
TI  - India launches air quality index to tackle pollution problems.

PMID- 25869533
TI  - Publication bias skewed results of anxiety drug treatment trials, study finds.

PMID- 25869532
TI  - Effect of sodium bicarbonate and varying concentrations of sodium chloride in
      brine on the liquid retention of fish (Pollachius virens L.) muscle.
AB  - BACKGROUND: Negative health effects associated with excessive sodium (Na) intake
      have increased the demand for tasty low-Na products (<2% NaCl) rather than
      traditional heavily salted fish products (~20% NaCl). This study investigates the
      causes of improved yield and liquid retention of fish muscle brined with a
      combination of salt (NaCl) and sodium bicarbonate (NaHCO3 ). RESULTS: Water
      characteristics and microstructure of saithe (Pollachius virens L.) muscle brined
      in solutions of NaCl and NaHCO3 or NaCl alone were compared using low-field
      nuclear magnetic resonance (LF-NMR) T2 relaxometry, microscopy, salt content,
      liquid retention and colorimetric measurements. Saithe muscle was brined for 92 h
      in 0, 30, 60, 120 or 240 g kg(-1) NaCl or the respective solutions with added 7.5
      g kg(-1) NaHCO3 . NaHCO3 inclusion improved the yield in solutions ranging from 0
      to 120 g kg(-1) NaCl, with the most pronounced effect being observed at 30 g kg(
      1) NaCl. The changes in yield were reflected in water mobility, with
      significantly shorter T2 relaxation times in all corresponding brine
      concentrations. Salt-dependent microstructural changes were revealed by light
      microscopy, where NaHCO3 supplementation resulted in greater intracellular space
      at 30 and 60 g kg(-1) NaCl. CONCLUSION: Sodium bicarbonate addition to low-salt
      solutions can improve yield and flesh quality of fish muscle owing to altered
      water mobility and wider space between the muscle cells.

PMID- 25869534
TI  - Stroke and periodontal disease in Senegal: case-control study.
AB  - OBJECTIVE: To determine the periodontal factors associated with stroke in
      melanodermic subjects in Senegal. STUDY DESIGN: Case-control study. METHODS: One
      hundred and twenty cases and 120 controls were included in this study. Cases had
      been diagnosed with stroke by a neurologist, with the diagnosis confirmed by
      scanner. Controls had never had any type of stroke. Data were collected regarding
      sociodemographic characteristics, lifestyle behaviours, general history, type of
      stroke (ischaemic or haemorrhagic) and periodontal parameters [plaque index,
      papillary bleeding index, pocket depth, clinical attachment loss, Community
      Periodontal Index of Treatment Needs and periodontitis (defined by clinical
      attachment loss >2 mm and pocket depth >3 mm)]. Logistic regression analysis was
      performed using R software to isolate a final model after adjustment for the 5%
      threshold. RESULTS: All periodontal characteristics were more common among cases
      than among controls. Periodontitis (odds ratio 1.58, 95% confidence interval 1.1
      3.022) and periodontal parameters were significantly associated with stroke,
      adjusted for hypertension, sedentary lifestyle, and the interaction between
      periodontitis and age. CONCLUSIONS: Periodontal disease is associated with stroke
      in the Senegalese population. Prospective longitudinal studies should be
      undertaken to improve understanding.

PMID- 25869536
TI  - Increased IL-9 mRNA expression as a biomarker to diagnose childhood tuberculosis
      in a high burden settings.

PMID- 25869535
TI  - Triazolophostins: a library of novel and potent agonists of IP3 receptors.
AB  - IP3 receptors are channels that mediate the release of Ca(2+) from the
      intracellular stores of cells stimulated by hormones or neurotransmitters.
      Adenophostin A (AdA) is the most potent agonist of IP3 receptors, with the beta
      anomeric adenine contributing to the increased potency. The potency of AdA and
      its stability towards the enzymes that degrade IP3 have aroused interest in AdA
      analogs for biological studies. The complex structure of AdA poses problems that
      have necessitated optimization of synthetic conditions for each analog. Such
      lengthy one-at-a-time syntheses limit access to AdA analogs. We have addressed
      this problem by synthesizing a library of triazole-based AdA analogs,
      triazolophostins, by employing click chemistry. An advanced intermediate having
      all the necessary phosphates and a beta-azide at the anomeric position was
      reacted with various alkynes under Cu(i) catalysis to yield triazoles, which upon
      deprotection gave triazolophostins. All eleven triazolophostins synthesized are
      more potent than IP3 and some are equipotent with AdA in functional analyses of
      IP3 receptors. We show that a triazole ring can replace adenine without
      compromising the potency of AdA and provide facile routes to novel AdA analogs. 

PMID- 25869537
TI  - Environmental temperature impacts on the performance of QuantiFERON-TB Gold In
      Tube assays.

PMID- 25869538
TI  - Naturally acquired antibody responses to recombinant Pfs230 and Pfs48/45
      transmission blocking vaccine candidates.
AB  - OBJECTIVES: Pfs48/45 and Pfs230 are Plasmodium falciparum sexual stage proteins
      and promising malaria transmission-blocking vaccine candidates. Antibody
      responses against these proteins may be naturally acquired and target antigens
      may be under selective pressure. This has consequences for the future evaluation
      of vaccine immunogenicity and efficacy in populations naturally exposed to
      malaria. METHODS: We determined naturally acquired antibody responses to the
      recombinant proteins Pfs48/45-10C and Pfs230-230CMB in children from three
      malaria endemic settings in Ghana, Tanzania and Burkina Faso. We also examined
      genetic polymorphisms in the P. falciparum gene pfs48/45. RESULTS: Antibody
      prevalence was 1.1-18.2% for 10C and 6.7-18.9% for 230CMB. In Burkina Faso we
      observed evidence of an age-dependent acquisition pattern for both 10C (p <
      0.001) and 230CMB (p = 0.031). Membrane feeding assays on a separate dataset
      demonstrated an association between functional transmission reducing activity and
      antibody prevalence for both 10C (p = 0.017) and 230CMB (p = 0.049). 17 single
      nucleotide polymorphisms were found in pfs48/45 (from 126 samples), with 5 non
      synonymous SNPs in the Pfs48/45 10C region. CONCLUSIONS: We conclude there are
      naturally acquired antibody responses to both vaccine candidates which have
      functional relevance by reducing the transmissibility of infected individuals. We
      identified genetic polymorphisms, in pfs48/45 which exhibited geographical
      specificity.

PMID- 25869539
TI  - Intravenous immunoglobulin use in septic shock patients after emergency
      laparotomy.
AB  - OBJECTIVES: The role of intravenous immunoglobulin (IVIG) as an adjunctive
      treatment for abdominal sepsis remains controversial. METHODS: Mechanically
      ventilated septic shock patients following emergency laparotomy for perforation
      of the lower intestinal tract were identified in the Japanese Diagnosis Procedure
      Combination inpatient database from July 2010 to March 2013. The effect of IVIG
      use on 28-day mortality was evaluated using propensity score and instrumental
      variable analyses. RESULTS: Eligible patients (n = 4919) treated at 845 hospitals
      were divided into IVIG (n = 2085) and control (n = 2834) groups. Propensity score
      matching created a matched cohort of 1081pairs with and without IVIG treatment.
      Although significant mortality differences existed between the IVIG and control
      groups in the unmatched analysis (20.6% vs. 18.3%; difference, 2.3%; 95%
      confidence interval [CI], 0.07-4.5), there were no significant differences in the
      propensity score-matched analysis (20.4% vs. 19.3%; difference, 1.1%; 95% CI, 
      2.3-4.5). Analysis employing the pattern of hospital IVIG use as an instrumental
      variable showed that IVIG use was not associated with reduced mortality
      (difference -2.5; 95% CI, -6.5-1.6). CONCLUSIONS: There may be no significant
      association between IVIG use and mortality in mechanically ventilated septic
      shock patients after emergency laparotomy.

PMID- 25869540
TI  - Configuration interaction singles based on the real-space numerical grid method:
      Kohn-Sham versus Hartree-Fock orbitals.
AB  - We developed a program code of configuration interaction singles (CIS) based on a
      numerical grid method. We used Kohn-Sham (KS) as well as Hartree-Fock (HF)
      orbitals as a reference configuration and Lagrange-sinc functions as a basis set.
      Our calculations show that KS-CIS is more cost-effective and more accurate than
      HF-CIS. The former is due to the fact that the non-local HF exchange potential
      greatly reduces the sparsity of the Hamiltonian matrix in grid-based methods. The
      latter is because the energy gaps between KS occupied and virtual orbitals are
      already closer to vertical excitation energies and thus KS-CIS needs small
      corrections, whereas HF results in much larger energy gaps and more diffuse
      virtual orbitals. KS-CIS using the Lagrange-sinc basis set also shows a better or
      a similar accuracy to smaller orbital space compared to the standard HF-CIS using
      Gaussian basis sets. In particular, KS orbitals from an exact exchange potential
      by the Krieger-Li-Iafrate approximation lead to more accurate excitation energies
      than those from conventional (semi-) local exchange-correlation potentials. 

PMID- 25869541
TI  - Data triangulation in the context of opioids monitoring via wastewater analyses.
AB  - BACKGROUND: The need to contextualise wastewater-based figures about illicit drug
      consumption by comparing them with other indicators has been stressed by numerous
      studies. The objective of the present study was to further investigate the
      possibility of combining wastewater data to conventional statistics to assess the
      reliability of the former method and obtain a more balanced picture of illicit
      drug consumption in the investigated area. METHODS: Wastewater samples were
      collected between October 2013 and July 2014 in the metropolitan area of Lausanne
      (226,000 inhabitants), Switzerland. Methadone, its metabolite 2-ethylidene-1,5
      dimethyl-3,3-diphenylpyrrolidine (EDDP), the exclusive metabolite of heroin, 6
      monoacetylmorphine (6-MAM), and morphine loads were used to estimate the amounts
      of methadone and heroin consumed. RESULTS: Methadone consumption estimated from
      EDDP was in agreement with the expectations. Heroin estimates based on 6-MAM
      loads were inconsistent. Estimates obtained from morphine loads, combined to
      prescription/sales data, were in agreement with figures derived from syringe
      distribution data and general population surveys. CONCLUSIONS: The results
      obtained for methadone allowed assessing the reliability of the selected sampling
      strategy, supporting its ability to capture the consumption of a small cohort
      (i.e., 743 patients). Using morphine as marker, in combination with
      prescription/sales data, estimates in accordance with other indicators about
      heroin use were obtained. Combining different sources of data allowed
      strengthening the results and suggested that the different indicators (i.e.,
      administration route, average dosage and number of consumers) contribute to
      depict a realistic representation of the phenomenon in the investigated area.
      Heroin consumption was estimated to approximately 13 gd ay(-1) (118 g day(-1) at
      street level).

PMID- 25869542
TI  - Racial/ethnic differences in trends in heroin use and heroin-related risk
      behaviors among nonmedical prescription opioid users.
AB  - BACKGROUND: This study examines changing patterns of past-year heroin use and
      heroin-related risk behaviors among individuals with nonmedical use of
      prescription opioids (NMUPO) by racial/ethnic groups in the United States.
      METHODS: We used data from the National Survey on Drug Use and Health (NSDUH)
      from 2002 to 2005 and 2008 to 2011, resulting in a total sample of N = 448,597.
      RESULTS: Past-year heroin use increased among individuals with NMUPO and
      increases varied by frequency of past year NMUPO and race/ethnicity. Those with
      NMUPO in the 2008-2011 period had almost twice the odds of heroin use as those
      with NMUPO in the 2002-2005 period (OR = 1.89, 95%CI: 1.50, 2.39), with higher
      increases in non-Hispanic (NH) Whites and Hispanics. In 2008-2011, the risk of
      past year heroin use, ever injecting heroin, past-year heroin abuse or
      dependence, and the perception of availability of heroin increased as the
      frequency of NMUPO increased across respondents of all race/ethnicities.
      CONCLUSION: Individuals with NMUPO, particularly non-Hispanic Whites, are at high
      risk of heroin use and heroin-related risk behaviors. These results suggest that
      frequent nonmedical users of prescription opioids, regardless of race/ethnicity,
      should be the focus of novel public health efforts to prevent and mitigate the
      harms of heroin use.

PMID- 25869543
TI  - Impaired Bayesian learning for cognitive control in cocaine dependence.
AB  - BACKGROUND: Cocaine dependence is associated with cognitive control deficits.
      Here, we apply a Bayesian model of stop-signal task (SST) performance to further
      characterize these deficits in a theory-driven framework. METHODS: A "sequential
      effect" is commonly observed in SST: encounters with a stop trial tend to prolong
      reaction time (RT) on subsequent go trials. The Bayesian model accounts for this
      by assuming that each stop/go trial increases/decreases the subject's belief
      about the likelihood of encountering a subsequent stop trial, P(stop), and that
      P(stop) strategically modulates RT accordingly. Parameters of the model were
      individually fit, and compared between cocaine-dependent (CD, n = 51) and healthy
      control (HC, n = 57) groups, matched in age and gender and both demonstrating a
      significant sequential effect (p < 0.05). Model-free measures of sequential
      effect, post-error slowing (PES) and post-stop slowing (PSS), were also compared
      across groups. RESULTS: By comparing individually fit Bayesian model parameters,
      CD were found to utilize a smaller time window of past experiences to anticipate
      P(stop) (p < 0.003), as well as showing less behavioral adjustment in response to
      P(stop) (p < 0.015). PES (p = 0.19) and PSS (p = 0.14) did not show group
      differences and were less correlated with the Bayesian account of sequential
      effect in CD than in HC. CONCLUSIONS: Cocaine dependence is associated with the
      utilization of less contextual information to anticipate future events and
      decreased behavioral adaptation in response to changes in such anticipation.
      These findings constitute a novel contribution by providing a computationally
      more refined and statistically more sensitive account of altered cognitive
      control in cocaine addiction.

PMID- 25869545
TI  - Efficacy and safety of telbivudine in different trimesters of pregnancy with high
      viremia for interrupting perinatal transmission of hepatitis B virus.
AB  - AIM: We aimed to investigate the efficacy and safety of telbivudine (LdT) on the
      intervention of mother-to-child transmission (MTCT) in different trimesters of
      pregnant women with high viral loads. METHODS: In this prospective cohort study,
      160 cases of mothers with high viral loads were included. Eighty-two subjects
      received 600 mg/day LdT therapy. Fifty of them started LdT therapy before the
      third trimester of gestation, including 17 cases before pregnancy, nine and 24
      cases in the first and second trimesters of pregnancy, respectively. The other 32
      cases started LdT in the third trimester of gestation. Control pregnant women (78
      cases) did not take LdT therapy. MTCT rate was determined by hepatitis B surface
      antigen (HBsAg) and hepatitis B virus (HBV) DNA data of infants at the 51st week
      post-partum. Adverse events were also evaluated throughout the study. RESULTS:
      One hundred and sixty infants were born from 160 pregnant women. Both LdT-treated
      groups displayed a marked decline in HBV DNA levels from the beginning to
      delivery. Positive rate of serum HBsAg in infants born from the above two groups
      of mothers were 0% and 3.1%, respectively, which was significantly lower than
      that in the untreated controls (24.4%). The incidence of detectable HBV DNA
      levels was significantly lower in infants born to LdT-treated mothers than in the
      controls (16.7%) at the 51st week post-partum. No infant had birth defects. No
      severe adverse event or complication were observed in LdT-treated mothers or
      infants followed until the 51st week post-partum. CONCLUSION: The earlier
      application of LdT during pregnancy, the better preventive effects it offered on
      MTCT.

PMID- 25869544
TI  - Factors affecting repeated cessations of injecting drug use and relapses during
      the entire injecting career among the Edinburgh Addiction Cohort.
AB  - BACKGROUND AND AIMS: Injecting drug use is a chronic condition, with people who
      inject drugs (PWID) typically experiencing repeated cessations and relapses
      during their injection careers. We characterize patterns of ceasing and relapsing
      and the impact of opiate substitution treatment (OST) during the entire injecting
      careers of PWID in the Edinburgh Addiction Cohort (EAC). METHODS: During 2005
      2007, 432 surviving participants of the EAC were interviewed about their
      injecting histories. Adjusted associations between covariates and hazards of
      cessation and relapse were estimated using random-effects models. RESULTS: OST
      was strongly associated with a higher hazard of cessation (HR = 1 .71, P <
      0.001), but there was no significant evidence of association with hazard of
      relapse (HR = 0.81, P = 0.14). Women and older PWID were less likely to relapse
      (HR = 0.73, P = 0.02 and HR = 0.55, P < 0.001, respectively). Hazards of both
      cessation and relapse decreased monotonically with time since last
      relapse/cessation (both P < 0.001). An individual's hazard of cessation increased
      with his/her number of previous cessations (HR = 3.58 for 10+ previous
      cessations, P < 0.001), but there was no evidence that an individual's hazard of
      relapse changed with number of previous relapses (P = 0.37). There was
      heterogeneity in the individual hazards of both cessation and relapse.
      CONCLUSIONS: OST was associated with reduced time to cessation, and there was
      some suggestion of increased time to relapse too. The likelihood of prolonged
      cessation is greater for women, increases with age, and decreases with time since
      last relapse.

PMID- 25869547
TI  - Predatory publishing and you.

PMID- 25869548
TI  - PrEP works and is a valuable addition to the HIV prevention toolkit.

PMID- 25869549
TI  - Year of ethics.

PMID- 25869550
TI  - Enough is enough.

PMID- 25869551
TI  - Metals distribution in colorectal biopsies: New insight on the elemental
      fingerprint of tumour tissue.
AB  - BACKGROUND: Some studies have linked colorectal cancer to metal exposure. AIMS:
      Our objective was to evaluate the element distribution in colorectal
      adenocarcinoma biopsies, adjacent non-tumour tissues, and healthy controls.
      METHODS: The study is a case-control study which compared the element
      distribution in colon biopsies from two groups of patients: with colorectal
      cancer (2 types of samples: colorectal cancer biopsies and adjacent non-tumour
      tissues) and healthy controls. Fifteen metal concentrations (Aluminium, Boron,
      Cadmium, Chromium, Copper, Iron, Magnesium, Manganese, Nickel, Lead, Selenium,
      Silicon, Titanium, Vanadium, and Zinc) were quantified by using inductively
      coupled plasma atomic emission spectrometry. RESULTS: 104 patients were included:
      76 in the colorectal cancer group, 28 in the healthy control group. Among the 15
      elements analyzed, only boron, chromium, zinc, silicon and magnesium were found
      at clearly detectable concentrations. Colorectal tumour biopsies had
      significantly higher concentrations of magnesium as compared to adjacent non
      tumour or healthy tissues. Zinc concentration followed the same trend but
      differences were not statistically significant. In addition, concentration of
      silicon was higher in colorectal cancer tissue than in healthy non-cancer tissue,
      while chromium was mostly found in adjacent non-tumour tissue. CONCLUSION:
      Magnesium, chromium, zinc and silicon were found in noteworthy concentrations in
      colorectal tumour. Their potential role in colorectal carcinogenesis should be
      explored.

PMID- 25869552
TI  - Risk factors for malignant progression of intraductal papillary mucinous
      neoplasms.
AB  - BACKGROUND: Intraductal papillary mucinous neoplasms of the pancreas are
      increasingly diagnosed. Due to their malignant potential, greater understanding
      of their nature is required. AIMS: Define risk factors for malignancy in
      intraductal papillary mucinous neoplasms. METHODS: An international, multicentre
      study was performed in Europe and the United States. Clinical databases were
      reviewed for patients with intraductal papillary mucinous neoplasms diagnosis.
      RESULTS: Of 1126 patients, 84 were diagnosed with invasive carcinoma/high-grade
      dysplasia and were compared to the rest of the cohort. Multivariate logistic
      analysis showed a statistically significant association between cancer/high-grade
      dysplasia and the variables smoking history (OR 1.9, 95% CI [1.1-3.1]), body mass
      index (OR 1.1, 95% CI [1-1.1]), symptoms (OR 3.4, 95% CI [1.9-6]), jaundice (OR
      0.1, 95% CI [0-0.3]), and steatorrhea (OR 0.3, 95% CI [0.1-0.8]). Univariate
      analysis showed no association between malignancy and the cyst number/location
      (p=0.3 and p=0.5, respectively) although a strong association was shown for cyst
      size (p<0.001). The presence and size of nodules (p<0.01) and main duct
      involvement (p<0.001) were also strongly related with malignancy. CONCLUSION: The
      presence of jaundice and steatorrhea, smoking, high body mass index, and imaging
      features such as cyst size, main duct involvement, and the presence and size of
      mural nodules are associated with high-grade neoplasia in intraductal papillary
      mucinous neoplasms.

PMID- 25869553
TI  - A prospective comparison of performance during back-to-back, anterograde manual
      spiral enteroscopy and double-balloon enteroscopy.
AB  - BACKGROUND: Spiral enteroscopy is a recently introduced technology alternative to
      balloon-assisted enteroscopy for examination of the small bowel. AIM: To compare
      small bowel insertion depths and procedure duration by spiral enteroscopy and
      double-balloon enteroscopy performed in the same cohort of patients, in immediate
      succession, using the same method of insertion depth estimation. METHODS: A
      prospective, back-to-back comparative study was performed in 15 patients. Spiral
      enteroscopy procedures were performed first and a tattoo was placed to mark the
      most distal point. RESULTS: Double-balloon enteroscopy passed the tattoo placed
      at spiral enteroscopy in 14/15 cases (93%). Median insertion depths for double
      balloon enteroscopy and spiral enteroscopy were 265cm and 175cm, respectively
      (P=0.004). Median time to achieve maximal depth of insertion was significantly
      shorter for spiral enteroscopy compared with double-balloon enteroscopy (24min
      vs. 45min, respectively; P=0.0005). However, in 14 patients no differences were
      found in median time to reach the same insertion depth (P=0.28). CONCLUSION:
      Double-balloon enteroscopy achieved significantly greater small bowel insertion
      depth than spiral enteroscopy. Although overall double-balloon enteroscopy
      procedure duration was longer, the time taken to reach the same small bowel
      insertion depth by both spiral enteroscopy and double-balloon enteroscopy was
      similar.

PMID- 25869554
TI  - Pre-pyloric pseudomelanosis.

PMID- 25869556
TI  - Advances in the analytical methodologies: Profiling steroids in familiar pathways
      challenging dogmas.
AB  - The comprehensive evaluation of the adrenal steroidogenic pathway, given its
      complexity, requires methodology beyond the standard techniques currently
      employed. Advances in LC-MS/MS, coupled with in vitro cell models that produce
      all the steroid metabolites of the mineralo-, glucocorticoid and androgen arms,
      present a powerful approach for the comprehensive evaluation of adrenal
      steroidogenesis in response to compounds of interest including bioactives, drug
      treatments and endocrine disrupting compounds. UHPLC-MS/MS analysis of steroid
      panels in forskolin, angiotensin II and K(+) stimulated H295R cells provides a
      snapshot of their effect on intermediates and end products of adrenal
      steroidogenesis. The impact of full steroid panel evaluations by LC- and GC-MS/MS
      extends to clinical profiling with the characterization of normal pediatric
      steroid reference ranges in sexual development and of disease-specific profiles
      improving diagnosis and sub classification. Comprehensive analyses of steroid
      profiles may potentially improve patient outcomes together with the application
      of treatments specifically suited to clinical subgroups. LC-MS/MS and GC-MS/MS
      applications in the analyses of comprehensive steroid panels are demonstrated in
      clinical conditions such as congenital adrenal hyperplasia in newborns requiring
      accurate diagnoses and in predicting metabolic risk in polycystic ovary syndrome
      patients. Most notable perhaps is the impact of LC-MS/MS evaluations on our
      understanding of the basic biochemistry of steroidogenesis with the detection of
      the long forgotten adrenal steroid, 11beta-hydroxyandrostenedione, at significant
      levels. The characterization of its metabolism to androgen receptor ligands in
      the LNCaP prostate cancel cell model, specifically within the context of
      recurring prostate cancer, lends new perspectives to old dogmas. We demonstrate
      that UHPLC-MS/MS has enabled the analyses of novel metabolites of the enzymes,
      SRD5A, 11betaHSD and 17betaHSD, in LNCaP cells. Undoubtedly, the continuous
      advances in the analytical methodologies used for steroid profiling and
      quantification will give impetus to the unraveling of the remaining enigmas, old
      and new, of both hormone biosynthesis and metabolism. 

PMID- 25869555
TI  - Gender Expression and Risk of HIV Infection Among Black South African Men Who
      Have Sex with Men.
AB  - To explore demographic, behavioral and psychosocial risk factors for HIV
      infection in South African MSM we recruited 480 MSM (aged 18 and 44 years) using
      respondent-driven sampling. Data were collected through individual computer
      assisted face-to-face interviews. Participants were tested for HIV. RDS-adjusted
      HIV prevalence is 30.1 % (unadjusted 35.6 %). Few participants had ever engaged
      in both receptive and insertive anal sex; sex with women was frequently reported.
      Independent demographic and behavioral correlates of HIV infection include age,
      education, number of male sexual partners, ever having been forced to have sex,
      and ever having engaged in transactional sex; engagement in sex with women was a
      protective factor. Psychosocial risk factors independently associated with HIV
      infection were feminine identification, internalized homophobia, and hazardous
      drinking. Our findings confirm what has been found in other studies, but also
      suggest that the dynamics and context of sexual transmission among MSM in South
      Africa differ from those among MSM in Western countries. 

PMID- 25869557
TI  - Environmental pollutants directly affect the liver X receptor alpha activity:
      Kinetic and thermodynamic characterization of binding.
AB  - Liver X receptor is a ligand-activated transcription factor, which is mainly
      involved in cholesterol homeostasis, bile acid and triglycerides metabolism, and,
      as recently discovered, in the glucose metabolism by direct regulation of liver
      glucokinase. Its modulation by exogenous factors, such as drugs, industrial by
      products, and chemicals is documented. Owing to the abundance of these synthetic
      molecules in the environment, and to the established target role of this
      receptor, a number of representative compounds of phthalate, organophosphate and
      fibrate classes were tested as ligands/modulators of human liver X receptor,
      using an integrated approach, combining an in silico molecular docking technique
      with an optical SPR biosensor binding study. The compounds of interest were
      predicted and proved to target the oxysterols-binding site of human LXRalpha with
      measurable binding kinetic constants and with affinities ranging between 4.3 *
      10(-7) and 4.3 * 10(-8)M. Additionally, non-cytotoxic concentration of these
      chemicals induced relevant changes in the LXRalpha gene expression levels and
      other target genes (SREBP-1c and LGK) in human liver hepatocellular carcinoma
      cell line (HepG2), as demonstrated by q-RT-PCR.

PMID- 25869558
TI  - Control of gene expression by novel metabolic intermediates.
AB  - In view of the recent discoveries of novel nuclear receptors (NRs) whose ligands
      remain to be determined, metabolic intermediates may be considered as ligands for
      these receptors and undiscovered or overlooked intermediates may play important
      roles in regulating gene expression by activating or repressing the action of
      these nuclear receptors. This article is part of a Special Issue entitled
      'Steroid Perspectives'. 

PMID- 25869559
TI  - Contemporary skull development - palatal angle analysis.
AB  - OBJECTIVES: The palatal angle is an important angle of the craniofacial complex.
      It is significant for the diagnosis of craniofacial disorders mainly for
      nasopharyngeal soft-tissue patterns.Background The dentists and
      otorhinolaryngologists use this relationship to establish proper treatment
      mechanics and evaluate facial profile. The aims of this study were to provide
      comparative cephalometric analyses of historical and contemporary skulls.
      MATERIALS AND METHOD: A total of 190 cephalograms of 2 groups of subjects were
      evaluated. Dolphin Imaging 11.0 - Cephalometric Tracing Analysis was used for the
      analysis. Unpaired two-tailed t-test assuming equality of variances was used for
      all variables (at the significance level p = 0.0001). RESULTS: The -modern
      forensic skulls had larger palatal angle at average value of 8.60 degrees +/-
      4.35, than that of archeological ones, the average value of which was 6.50
      degrees +/- 3.92. The difference was found significant. Unpaired two-tailed t
      test assuming equality of variances showed that historical and contemporary
      skulls had statistically significant results. The difference was -2.09 with
      standard error of 0.60 (95% confidence interval from -3.29 to -0.89). Two-tailed
      probability attained value of P was less than 0.0001. CONCLUSION: The difference
      between both groups was found significant. An increase in the palatal angle can
      be directly connected with anterior rotation of upper jaw(Tab. 2, Fig. 5, Ref.
      19).

PMID- 25869560
TI  - Soluble P-selectin glycoprotein ligand - a possible new target in ulcerative
      colitis.
AB  - BACKGROUND: The main characteristic of active inflammatory bowel disease (IBD) is
      the neutrophil infiltration into the intestinal lamina propria, where neutrophils
      usually do not reside. Selectins are cell surface glycoproteins responsible for
      binding the leukocytes to vascular cells and their extravasation into the
      surrounding tissue. They show high affinity to P-selectin glycoprotein ligand-1
      (PSGL-1) receptors. PSGL-1 is expressed on the surface of all leukocytes and they
      mediate the rolling of neutrophils on P-selectin. Soluble PSGL-1 acts
      competitively with cellular PSGL in many physiological and pathological
      processes.The aim of our study was to compare serum sPSGL-1 concentration in the
      blood of patients with ulcerative colitis (UC) and healthy control subjects.
      METHODS: Serum concentrations of sPSGL-1 were measured in 20 patients with UC and
      20 control subjects. Two-layer immunoenzyme procedure (ELISA) was used. RESULTS:
      The mean (+/- standard deviation) serum concentrations of sPSGL-1 in patients
      with UC and controls were 349.97+/-75.40 U/mL and 284.39+/-52.40 U/mL,
      respectively (p=0.003). CONCLUSION: In the present study, we showed that patients
      with UC had significantly higher sPSGL-1 blood values in comparison with healthy
      subjects. A short-term blockade with anti-PSGL-1 antibodies could block the
      transport of neutrophils and decrease UC activity. Thus it could possibly be
      employed in a new therapeutic approach to the treatment of UC (Fig. 1, Ref. 25).

PMID- 25869561
TI  - Influence of Rho kinase inhibitor fasudil on late endothelial progenitor cells in
      peripheral blood of COPD patients with pulmonary artery hypertension.
AB  - OBJECTIVE: To investigate the influence of Fasudil, a Rho inhibitor on the number
      and functions of the late endothelial progenitor cells in peripheral blood of
      chronic obstructive pulmonary diseases (COPD) patients with pulmonary artery
      hypertension. BACKGROUND: It is not clear yet, whether Rho Kinase Inhibitor
      Fasudil can reduced pulmonary artery pressure through improving lung endothelial
      function. METHODS: 80 COPD patients with pulmonary artery hypertension were
      selected and divided into two groups: the treatment group and the control group,
      which had 40 patients, respectively. Changes in the number and function of the
      late endothelial progenitor cells in peripheral blood of the patients before and
      after the treatment were compared between the two groups. The changes on the
      pulmonary artery pressure were also compared. RESULTS: The number of the late
      endothelial progenitor cells in peripheral blood of the treatment group increased
      and the function was enhanced. The pulmonary artery pressure was reduced. The
      difference before and after the treatment and with the control group was
      statistically significant (p < 0.05). CONCLUSIONS: The Rho-kinase inhibitor
      Fasudil increased the number and enhanced the function of the late endothelial
      progenitor cells in peripheral blood of COPD patients with pulmonary artery
      hypertension (Tab. 3, Fig. 2, Ref. 17).

PMID- 25869563
TI  - Methylene blue as an antioxidant agent in experimentally-induced injury in rat
      liver.
AB  - BACKGROUND: We aimed to test the methylene blue (MB) as a dye and also to test
      its antioxidant activities in devascularization-induced liver injury. METHODS:
      Twenty rats weighing 240-280 g were randomly divided into two groups, each
      containing 10 rats. High-grade liver injury was induced by using a pair of long
      pliers with blades. MB was injected into portal vein of the rats with no hepatic
      injury (Group 1; control group) and those with injured livers (Group 2; injury
      group). Liver and hepatic function tests, paraoxonase, stimulated paraoxonase,
      arylesterase activity, total antioxidant, and oxidant status were evaluated
      before and 24 h after MB injection. RESULTS: MB did not stain the non-perfused
      area. Total antioxidant status decreased significantly in Group 2 at hour 24
      compared to Group 1. In Group 2, total antioxidant status was lower at hour 24
      compared to hour 0. Total oxidant status in Group 2 at hour 0 increased
      significantly compared to Group 1. Total oxidant status in Group 2 at hour 24 was
      lower compared to that at hour 0. Lipid peroxidation parameters did not alter due
      to devascularization. CONCLUSION: MB is useful in defining the devascularization
      area. Moreover, it showed to have a beneficial effect on oxidant status (Tab. 3,
      Fig. 3, Ref. 25).

PMID- 25869562
TI  - Cytocompatibility of implants coated with titanium nitride and zirconium nitride.
AB  - INTRODUCTION: The positive cell response to the implant material is reflected by
      the capacity of cells to divide, which leads to the tissue regeneration and
      osseointegration. Technically pure titanium and its alloys are mostly used for
      implant manufacturing. These alloys have the adequate mechanical, physical and
      biological properties; nevertheless, the superior biocompatibility of bioceramics
      has been proven. With the arrival of new coating techniques, surface modification
      of materials used for implants has become a widely investigated issue. METHODS:
      The paper studied properties of titanium nitride (TiN) and zirconium nitride
      (ZrN) coatings deposited by PVD (Physical Vapour Deposition). Coatings were
      applied to substrates of pure titanium, Ti6Al4V, Ti35Nb6Ta titanium alloys and
      CoCrMo dental alloy. Different treatments of substrate surfaces were used:
      polishing, etching and grit blasting. Cytocompatibility tests assessed the cell
      colonization and their adherence to substrates. RESULTS AND CONCLUSION: Results
      showed that TiN layers deposited by PVD are suitable for coating all substrates
      studied. The polished samples and those with TiN coating exhibited a higher cell
      colonization. This coating technique meets the requirements for the
      biocompatibility of the implanted materials; furthermore, their colour range
      solves the issue of red aesthetics in oral implantology as the colour of these
      coatings prevents titanium from showing through the gingiva. This is one the most
      important criteria for the aesthetic success of implant therapy (Tab. 5, Ref.
      18).

PMID- 25869564
TI  - Effects of modafinil on pentylenetetrazol-induced convulsive epilepsy.
AB  - Modafinil, is a wake-promoting drug approved by Food and Drugs Administration
      (FDA) for narcolepsy and sleep-apnoe syndrome. Although the mechanism underlying
      its arousal action remains elusive, it is known to increase glutamatergic,
      histaminergic, noradrenergic and dopaminergic transmission and decrease GABA
      release in different regions of the brain, which are all known to be involved in
      pathophysiology of epilepsy. In the present study, the effects of modafinil on
      pentylenetetrazol (PTZ) induced convulsive epilepsy were investigated in rats.
      Five experimental groups were formed for this purpose and each group was
      administered five different doses of modafinil (1, 2, 4, 45, 180 mg/kg, i.p) for
      seven days. All groups were administered PTZ (80 mg/kg, i.p) 2 hours after the
      final dose and the epileptic seizure activity was evaluated. According to the
      results; we detected that modafinil delayed the onset of the first myoclonic jerk
      and decreased the total major seizure period between 2-180 mg/kg doses and did
      not affect the major seizure onset period at any of the doses administrated.
      These results imply that modafinil exerts a dose dependent antiepileptic effect
      on PTZ induced convulsive epilepsy in rats (Tab. 1, Fig. 3, Ref, 42). 

PMID- 25869565
TI  - Use of infliximab in treatment of acute pancreatitis.
AB  - OBJECTIVE: The aim of this study was to investigating the effects of infliximab
      in severe necrotizing pancreatitis. METHODS: Forty male Wistar rats were randomly
      divided into five groups evenly. Necrotizing pancreatitis was induced in group I
      and II by retrograde injection of 3% taurocholate into common pancreaticobiliary
      duct. In group III and IV saline was introduced instead of taurocholate to mimic
      pressure effect. Infliximab (8mg/kg) was infused through tail vein in group I and
      III and saline was infused in group II and IV just before laparotomy. Group V
      underwent sham laparotomy. Serum amylase activity, serum and tissue sialic acid,
      carbonyl content, malondialdehyde, total antioxidant activity (TAA) and
      pancreatic histopathology were assessed. RESULTS: In group I serum sialic acid,
      malondialdehyde, carbonyl content and amylase activity were significantly lower
      than in group II (p<0.01). There were no significant differences for serum TAA
      between group I and II (p>0.05). Tissue sialic acid and malondialdehyde in group
      I were significantly lower than in group II (p<0.01). But tissue TAA in group I
      was significantly higher than in group II (p<0.01). Carbonyl content of group I
      was not significantly different from group II (p>0.05). Histopathologically,
      pancreatic sections of group II demonstrated extensive acinar and fat necrosis,
      hemorrhage, and inflammation. In group I Infliximab improved histopathological
      changes (p0.05). CONCLUSION: Administration of infliximab resulted in a
      significant improvement in biochemical and histopathological alterations in acute
      necrotizing pancreatitis(Tab. 3, Ref. 43).

PMID- 25869566
TI  - Serum omentin levels predicts mesenteric ischemia.
AB  - BACKGROUND: Acute mesenteric ischemia (AMI) is an intestinal vascular disease
      with high mortality. Clinical diagnosis of acute mesenteric ischemia is
      difficult. Adipose tissue is an important mediator of metabolism and
      inflammation.Omentin is produced by visceral adipose tissue and decreased serum
      levels of omentin are associated with poor metabolic outcomes. We aimed to
      investigate whether serum omentin level predicts early diagnosis of AMI before
      development of transmural ischemia. METHODS: Twenty-four Sprague Dawley rats
      weighted about 200-250 gr grouped in 3 experimental groups as sham, transient
      ischemia and permanent ischemia. Each group consisted of 8 rats. Blood samples
      were evaluated to determine serum urea, creatinine, omentin and C-reactive
      protein (CRP) levels. A blinded histological examination performed with the same
      histologist for hemotoxileneosine painted ileal tissue samples. RESULTS: Mean
      serum omentin level in sham group (27.5+/-4.67) was significantly elevated
      compared to rats in Ischemia-reperfusion (IR) group (10.9+/-9.01).The difference
      reached the statistical significance (p=0.004). Serum omentin levels were not
      correlated to urea, creatinine or CRPlevels. CONCLUSION: Omentin levels may be a
      biochemical indicator to detect AMI. However, further human studies are needed
      (Tab. 3, Fig. 3, Ref. 34).

PMID- 25869567
TI  - Ameliorative effect of Leflunomide on lung injury following an aspiration.
AB  - BACKGROUND: We aimed to investigate the therapeutic effectiveness of leflunomide
      (LEF) in lung injury after an aspiration of unknown pathophysiology. MATERIAL AND
      METHODS: Forty-two healthy Sprague Dawley rats were anesthetized and allocated to
      six experimental groups: saline (S) aspirated, S+LEF, hydrochloric acid (HCl)
      aspirated, HCl+LEF, formula aspirated (FOR), and FOR+LEF. The treatment groups
      (S+LEF, HCl+LEF, and FOR+LEF) received 20 mg/kg/day intraperitoneal (i.p.)
      injection of LEF for seven days. At the end of the seven days, blood and tissue
      samples were taken from the rats for histopathological, biochemical, and
      immunohistochemical examination. RESULTS: There was a significant increase in
      serum levels of YKL-40, a chitinase-like protein, in the HCl group after the
      aspiration (p<0.01). The increase in serum YKL-40 levels decreased significantly
      with LEF treatment (p<0.01). There was no significant difference in serum YKL-40
      levels in the FOR group compared to the control group at pretreatment and in the
      FOR+LEF group at post-treatment. There was a significant increase in serum
      thiobarbituric acid-reactive species (TBARS) values in the HCl and FOR groups
      compared to the control group (p=0.001 and p<0.01, respectively). In both
      treatment groups, the serum TBARS values significantly decreased after treatment
      with LEF (p=0.001 and p<0.05, respectively). There was a significant improvement
      in the histopathological scores, which deteriorated after the aspiration, and in
      the number of inducible nitric oxide synthase (iNOS)-positive cells after
      treatment with LEF.

PMID- 25869568
TI  - Mechanism of protein phosphatase-2Aregulating phosphorylation of amyloid
      precursor proteosome and Abeta generation.
AB  - OBJECTIVE: To discuss whether PP-2A influences the phosphorylation level at APP
      threonine 668 locus thus regulating Abeta secretion. METHOD: In the experiment,
      24 hours after N2a cells of stably transfected human APP (N2a/APP) were treated
      with okadaic acid (OA) or DES (C6-ceramide) (N2a/APP), an injection of OA
      cerebral stereotactic was administered to a SD rat in the hippocampal region, or
      PP-2A overexpressed plasmids was transfected transiently, the aggregate levels of
      APP phosphorylated APP, and APP-CTF were detected through immunoblotting and the
      activity of PP-2A and secretase was also detected using a reagent kit. RESULT:
      The phosphorylation level of APP was significantly increased after the PP-2A
      activity was inhibited by OA. DES activated PP-2A or over-expressed PP-2A was
      able to reduce the phosphorylation level of APP. Either can inhibit PP and reduce
      the phosphorylation level of APP. The level of phosphorylated APP was increased
      significantly after the SD rat was injected with OA through the hippocampal
      region. The activity of beta- and gamma-secretases in N2a/APP cells significantly
      increased after OA treatment whereas the alpha-secretase activity had no
      significant changes; the Abeta level increased. CONCLUSION: We discovered that PP
      2A was capable of regulating the Abeta level by regulating APP phosphorylation
      level and beta and gamma-secretase activity(Fig. 5, Ref. 30).

PMID- 25869569
TI  - Evaluation of preemptive dexketoprofen trometamol effect on blood chemistry,
      vital signs and postoperative pain in dogs undergoing ovariohysterectomy.
AB  - OBJECTIVE: To investigate the postoperative analgesic effects of preemptive
      dexketoprofen trometamol in dogs subjected to ovariohysterectomy (OHE). MATERIAL
      AND METHODS: Seventeen adult bitches of various breeds were used in this study.
      The dogs were randomly allocated into of two groups. Subjects in the
      dexketoprofen trometamol (DEX) group (n=10), received intravenous (i.v.)
      dexketoprofen trometamol, 1 mg/kg, 15 minutes before premedication, while those
      assigned to the control (C) group (n=7) were given no analgesics prior to
      premedication. Pain level was assessed by two researchers before the
      administration of anaesthesia (15 minutes before start) and 0, 1, 2, 4 and 6
      hours after surgery. A modified University of Melbourne Pain Scale (UMPS) was
      used to evaluate pain in both groups. RESULTS: Serum cortisol level changed from
      0 to 1 h and from 0 to 1 to 4 h were compared between the groups; the increase in
      the C group was statistically significant. The modified UMPS was applied to both
      groups at baseline and postoperative 1, 2, 4 and 6 h. According to this test, the
      values for DEX were significantly lower than controls at 4 and 6 h (p<0.001).
      CONCLUSION: Stable vital signs with unchanged biochemical parameters on
      dexketoprofen administration are a promising finding. The clinical advantage
      shown by the pain scale difference and the low serum cortisol levels should
      qualify dexketoprofen for preemptive pain management in dogs (Tab. 5, Fig. 2,
      Ref. 30).

PMID- 25869570
TI  - Attenuation of bleomycin induced lung fibrosis by erdosteine and inhibition of
      the inducible nitric oxide synthase.
AB  - BACKGROUND AND OBJECTIVES: Despite advances in treatment modalities, the
      discovery of optimal medical therapies still remains a necessity in the
      management of pulmonary fibrosis. MATERIAL AND METHODS: The experiments were
      performed in 35 adult Sprague Dawley rats, randomly allotted into one of five
      groups (n=7). The control group was treated with 1 ml/kg, 0.9 % saline; the BLM
      group was given a single dose of BLM (2.5 U/kg); the BLM+ER group was treated
      with ER (10 mg/kg/day po) for 14 days after BLM administration; the BLM+SMT group
      was treated with i.p injections of SMT (20 mg/kg/ day) for 14 days after BLM
      administration; the BLM+ER+SMT group was treated with ER and SMT for 14 days
      after BLM administration. At the end of day 14, the results of histopathological,
      biochemical, and immunohistochemical investigations were analyzed. RESULTS: Serum
      TNF-alpha, nitrate/nitrite, and TBARS levels significantly increased in BLM group
      compared to control group (p < 0.001, p < 0.001 and p < 0.05 respectively). Lung
      tissue content of IL-6 was found to be lower in BLM+ER, BLM+SMT and BLM+ER+SMT
      groups compared to BLM group by immunhistochemical examinations (p < 0.01, p <
      0.01 and p < 0.001, respectively). Similarly, the TNF-alpha reactions (p < 0.01
      for each group) and NF-kB expressions were shown to be significantly different
      among the study groups (p < 0.05, p < 0.05 and p < 0.001, respectively).
      CONCLUSION: Based on our study, ER and SMT attenuate BLM-induced pulmonary
      fibrosis; the combination of two agents has a greater protective efficacy against
      fibrosis than one alone, reducing the inflammatory markers (Tab. 2, Fig. 2, Ref.
      31).

PMID- 25869571
TI  - Imported new world cutaneous leishmaniasis in a traveller from Slovakia.
AB  - We present a case of imported leishmaniasis in a 31-year-old woman from Slovakia,
      who visited the countries of South America for three months in 2011. On 29 and 31
      August 2011, she was probably infected with Leishmania parasites in the jungles
      of Ecuador. Approximately one week after returning to Slovakia, a small papules
      appeared on patient's left leg. Another wound was found after two weeks. Both
      ulcers were enlarging. We proved amastigote forms of Leishmania spp. only in
      repeated dermal scrapings from the edge of the ulcer by Giemsa staining after
      negative results from examination of a wound scrape and biopsy specimen. We
      identified the species Leishmania (Viannia) panamensis as a causative agent by
      using the polymerase chain reaction (PCR) method and subsequent sequencing of the
      ITS region. Closure of wounds and scab formation were observed after 20 days of
      treatment with sodium stibogluconate. In the control microscopic examination
      after the end of the treatment, parasites were not present, and the PCR confirmed
      the negative result (Fig. 2, Ref. 31).

PMID- 25869572
TI  - Diabetes: SDF-1 dysregulation mediates diabetic stem cell mobilopathy.

PMID- 25869573
TI  - Metabolism: Dietary emulsifiers--sweepers of the gut lining?

PMID- 25869574
TI  - A jack of all trades: the multiple roles of the unique essential second messenger
      cyclic di-AMP.
AB  - Second messengers are key components of many signal transduction pathways. In
      addition to cyclic AMP, ppGpp and cyclic di-GMP, many bacteria use also cyclic di
      AMP as a second messenger. This molecule is synthesized by distinct classes of
      diadenylate cyclases and degraded by phosphodiesterases. The control of the
      intracellular c-di-AMP pool is very important since both a lack of this molecule
      and its accumulation can inhibit growth of the bacteria. In many firmicutes, c-di
      AMP is essential, making it the only known essential second messenger. Cyclic di
      AMP is implicated in a variety of functions in the cell, including cell wall
      metabolism, potassium homeostasis, DNA repair and the control of gene expression.
      To understand the molecular mechanisms behind these functions, targets of c-di
      AMP have been identified and characterized. Interestingly, c-di-AMP can bind both
      proteins and RNA molecules. Several proteins that interact with c-di-AMP are
      required to control the intracellular potassium concentration. In Bacillus
      subtilis, c-di-AMP also binds a riboswitch that controls the expression of a
      potassium transporter. Thus, c-di-AMP is the only known second messenger that
      controls a biological process by interacting with both a protein and the
      riboswitch that regulates its expression. Moreover, in Listeria monocytogenes c
      di-AMP controls the activity of pyruvate carboxylase, an enzyme that is required
      to replenish the citric acid cycle. Here, we review the components of the c-di
      AMP signaling system. 

PMID- 25869575
TI  - Importance and impact of preanalytical variables on Alzheimer disease biomarker
      concentrations in cerebrospinal fluid.
AB  - BACKGROUND: Analyses of cerebrospinal fluid (CSF) biomarkers (beta-amyloid
      protein, total tau protein, and hyperphosphorylated tau protein) are part of the
      diagnostic criteria of Alzheimer disease. Different preanalytical sample
      procedures contribute to variability of CSF biomarker concentrations, hampering
      between-laboratory comparisons. The aim of this study was to explore the
      influence of fractionated sampling, centrifugation, freezing temperature,
      freezing delay, and freeze-thaw cycles on CSF biomarker analyses. METHODS: We
      studied fractionated sampling in sequential aliquots of lumbar CSF. Centrifuged
      and noncentrifuged samples from the same fraction were compared. CSF samples were
      subjected to different protocols (liquid nitrogen, -80  degrees C, and -20 
      degrees C; 24 h at 2-8  degrees C; and 24 and 48 h at room temperature). To study
      the influence of freeze-thaw cycles, samples were thawed up to 4 times and
      refrozen at -80  degrees C. CSF was collected in polypropylene tubes. We measured
      CSF biomarker concentrations with commercially available single-analyte Innotest
      assays. RESULTS: CSF biomarker concentrations from non-blood-contaminated samples
      are not influenced by centrifugation or fractionated sampling. Freezing
      temperature and delayed storage can affect biomarker concentrations; freezing of
      CSF samples at -80  degrees C as soon as possible after collection is
      recommended. Consecutive freezing and thawing of CSF samples up to 3 times had
      little effect. CONCLUSIONS: Temperature of freezing, delay until freezing, and
      freeze-thaw cycles significantly influence CSF biomarker concentrations,
      stressing the need for standard operating procedures for preanalytical sample
      handling. The differences observed in this study are, however, relatively small,
      and the impact on the clinical value of these CSF biomarkers needs to be
      determined.

PMID- 25869576
TI  - Preanalytical variables and Alzheimer disease biomarker concentrations in
      cerebrospinal fluid.

PMID- 25869577
TI  - Why disruptive innovations matter in laboratory diagnostics.

PMID- 25869578
TI  - Regulatory Forum Opinion Piece*: Dispelling Confusing Pathology Terminology:
      Recognition and Interpretation of Selected Rodent Renal Tubule Lesions.
AB  - Renal tubule lesions often prove troublesome for toxicologic pathologists because
      of the diverse nature and interrelated cell types within the kidney and the
      presence of spontaneous lesions with overlapping morphologies similar to those
      induced by renal toxicants. Although there are a number of guidance documents
      available citing straightforward diagnostic criteria of tubule lesions for the
      pathologist to refer to, most are presented without further advice on the when to
      or to the why and the why not of diagnosing one lesion over another. Documents
      presenting diagnostic perspectives and recommendations derived from an author's
      experience are limited since guidance documents are generally based on
      descriptive observations. In this Regulatory Forum opinion piece, the authors
      attempt to dispel confusing renal tubule lesion terminology in laboratory animal
      species by suggesting histological advice on the recognition and interpretation
      of these complex entities. 

PMID- 25869579
TI  - Mentoring Strategies and Outcomes of Two Federally Funded Cancer Research
      Training Programs for Underrepresented Students in the Biomedical Sciences.
AB  - The US is experiencing a severe shortage of underrepresented biomedical
      researchers. The purpose of this paper is to present two case examples of cancer
      research mentoring programs for underrepresented biomedical sciences students.
      The first case example is a National Institutes of Health/National Cancer
      Institute (NIH/NCI) P20 grant titled "South Carolina Cancer Disparities Research
      Center (SC CaDRe)" Training Program, contributing to an increase in the number of
      underrepresented students applying to graduate school by employing a triple-level
      mentoring strategy. Since 2011, three undergraduate and four graduate students
      have participated in the P20 SC CaDRe program. One graduate student published a
      peer-reviewed scientific paper. Two graduate students (50 %) have completed their
      master's degrees, and the other two graduate students will receive their degrees
      in spring 2015. Two undergraduate students (67 %) are enrolled in graduate or
      professional school (grad./prof. school), and the other graduate student is
      completing her final year of college. The second case example is a prostate
      cancer-focused Department of Defense grant titled "The SC Collaborative
      Undergraduate HBCU Student Summer Training Program," providing 24 students
      training since 2009. Additionally, 47 students made scientific presentations, and
      two students have published peer-reviewed scientific papers. All 24 students took
      a GRE test preparation course; 15 (63 %) have applied to graduate school, and 11
      of them (73 %) are enrolled in grad./prof. school. Thirteen remaining students
      (54 %) are applying to grad./prof. school. Leveraged funding provided research
      training opportunities to an additional 201 National Conference on Health
      Disparities Student Forum participants and to 937 Ernest E. Just Research
      Symposium participants at the Medical University of South Carolina. 

PMID- 25869580
TI  - Cancer Support Needs for African American Breast Cancer Survivors and Caregivers.
AB  - Improved cancer screening and treatment advances have led to higher cancer
      survival rates in the United States. However, racial disparities in breast cancer
      survival persist for African American women who experience lower survival rates
      than white women. These disparities suggest that unmet needs related to
      survivorship still exist. This study focuses on the challenges that both African
      American cancer survivors and caregivers face across the cancer continuum. Five
      African American focus groups examined cancer survivor and caregiver support
      needs. Focus groups were recorded, transcribed, and uploaded into Atlas.ti.
      Thematic content analysis was applied to the text during the coding process.
      Themes were identified and emphasized based on the research team's integrated and
      unified final codes. Forty-one African Americans participated in five focus
      groups: 22 cancer survivors and 19 caregivers. Participants discussed five
      themes: (1) a culture that discourages the discussion of cancer; (2) lack of
      support services for African American cancer survivors; (3) lack of support
      services for cancer caregivers; (4) need for culturally appropriate cancer
      resources, including resources targeted at African American women; and (5)
      aspects that were helpful to cancer survivors and caregivers, including
      connecting with other survivors and caregivers, and having strong social support
      networks. We gained new insight into the unmet support needs for survivors and
      caregivers, especially when coping with the cancer experience continuum. While
      some cancer and caregiver support services exist, our study reveals a great need
      for services that incorporate the cultural differences that exist across races. 

PMID- 25869581
TI  - Development and validation of a predictive risk model for all-cause mortality in
      type 2 diabetes.
AB  - AIMS: Type 2 diabetes is common and is associated with an approximate 80%
      increase in the rate of mortality. Management decisions may be assisted by an
      estimate of the patient's absolute risk of adverse outcomes, including death.
      This study aimed to derive a predictive risk model for all-cause mortality in
      type 2 diabetes. METHODS: We used primary care data from a large national multi
      ethnic cohort of patients with type 2 diabetes in New Zealand and linked
      mortality records to develop a predictive risk model for 5-year risk of
      mortality. We then validated this model using information from a separate cohort
      of patients with type 2 diabetes. RESULTS: 26,864 people were included in the
      development cohort with a median follow up time of 9.1 years. We developed three
      models initially using demographic information and then progressively more
      clinical detail. The final model, which also included markers of renal disease,
      proved to give best prediction of all-cause mortality with a C-statistic of 0.80
      in the development cohort and 0.79 in the validation cohort (7610 people) and was
      well calibrated. Ethnicity was a major factor with hazard ratios of 1.37 for
      indigenous Maori, 0.41 for East Asian and 0.55 for Indo Asian compared with
      European (P<0.001). CONCLUSIONS: We have developed a model using information
      usually available in primary care that provides good assessment of patient's risk
      of death. Results are similar to models previously published from smaller cohorts
      in other countries and apply to a wider range of patient ethnic groups.

PMID- 25869582
TI  - Dress induced by piperacillin-tazobactam in a child.

PMID- 25869583
TI  - Fish is a major trigger of solid food protein-induced enterocolitis syndrome in
      Spanish children.

PMID- 25869584
TI  - Factors associated with concordance with the non-level-A guideline
      recommendations for emergency department patients with acute asthma.

PMID- 25869586
TI  - Intensive care diaries to promote recovery for patients and families after
      critical illness: A Cochrane Systematic Review.
AB  - OBJECTIVES: To assess the effect of an intensive care unit (ICU) diary versus no
      ICU diary on patients, and their caregivers or families, during the patient's
      recovery from admission to an ICU. DESIGN: Systematic review of randomized
      controlled trials (RCTs) and clinical controlled trials. DATA SOURCES: CENTRAL,
      MEDLINE, CINAHL, EMBASE, PsycINFO, PILOT; Web of Science Conference Proceedings,
      clinical trial registries and reference lists of identified trials. REVIEW
      METHODS: Studies evaluated the effectiveness of patient diaries, when compared to
      no ICU diary, for patients or family members to promote recovery after admission
      to ICU were included. Outcome measures for describing recovery from ICU included
      the risk of post-traumatic stress disorder (PTSD), anxiety, depression and post
      traumatic stress symptomatology, health-related quality of life and costs. We
      used standard methodological approaches as expected by The Cochrane
      Collaboration. Two review authors independently reviewed titles for inclusion,
      extracted data and undertook risk of bias according to pre-specified criteria.
      RESULTS: We identified three eligible studies; two describing ICU patients
      (N=358), and one describing relatives of ICU patients (N=30). No study adequately
      reported on risk of PTSD as described using a clinical interview, family or
      caregiver anxiety or depression, health-related quality of life or costs. Within
      a single study there was no clear evidence of a difference in risk for developing
      anxiety (RR 0.29, 95% CI 0.07-1.19) or depression (RR 0.38, 95% CI 0.12-1.19) in
      participants who received ICU diaries, in comparison to those that did not
      receive a patient diary. Within a single study there was no evidence of
      difference in median post-traumatic stress symptomatology scores (diaries 24, SD
      11.6; no diary 24, SD 11.6) and delusional ICU memory recall (RR 1.04, 95% CI
      0.84-1.28) between the patients recovering from ICU admission who received
      patient diaries, and those who did not. One study reported reduced post-traumatic
      stress symptomatology in family members of patients recovering from admission to
      ICU who received patient diaries (median 19; range 14-28), in comparison to no
      diary (median 28; range 14-38). CONCLUSIONS: Currently there is minimal evidence
      from RCTs of the benefits or harms of patient diaries for patients and their
      caregivers or family members. A small study has described their potential to
      reduce post-traumatic stress symptomatology in family members. However, there is
      currently inadequate evidence to support their effectiveness in improving
      psychological recovery after critical illness for patients and their family
      members.

PMID- 25869585
TI  - Response to Nodal morphogen gradient is determined by the kinetics of target gene
      induction.
AB  - Morphogen gradients expose cells to different signal concentrations and induce
      target genes with different ranges of expression. To determine how the Nodal
      morphogen gradient induces distinct gene expression patterns during zebrafish
      embryogenesis, we measured the activation dynamics of the signal transducer Smad2
      and the expression kinetics of long- and short-range target genes. We found that
      threshold models based on ligand concentration are insufficient to predict the
      response of target genes. Instead, morphogen interpretation is shaped by the
      kinetics of target gene induction: the higher the rate of transcription and the
      earlier the onset of induction, the greater the spatial range of expression.
      Thus, the timing and magnitude of target gene expression can be used to modulate
      the range of expression and diversify the response to morphogen gradients. 

PMID- 25869587
TI  - In-Hospital Morbidity and Mortality Following Total Joint Arthroplasty in
      Patients with Hemoglobinopathies.
AB  - Given the growing patient population with hemoglobinopathies needing total joint
      arthroplasty (TJA) and paucity of literature addressing this cohort, we examined
      the in-hospital complications in patients with hemoglobinopathies undergoing TJA.
      International Classification of Diseases, Ninth Revision codes were used to
      search the Nationwide Inpatient Sample database for hemoglobinopathy patients
      undergoing primary or revision TJA. Hemoglobinopathy patients had a significant
      increase in cardiac, respiratory, and wound complications; blood product
      transfusion; pulmonary embolism; surgical site infection; and systemic infection
      events, while there was no significant effect on deaths, deep vein thrombosis,
      and renal complications. It may be prudent to implement blood conservation
      strategies as well as diligent postoperative protocols to minimize the need for
      transfusion and related complications in this patient population. 

PMID- 25869588
TI  - Midterm Outcomes of the Recently FDA Approved Ceramic on Ceramic Bearing in Total
      Hip Arthroplasty Patients Under 65 Years of Age.
AB  - The present study aimed to evaluate the mid-term results of the fourth generation
      of ceramic on ceramic (CC) bearing. Demographics, surgical technique,
      complications, clinical and radiologic outcomes were analyzed in a series of 133
      consecutive CC total hip arthroplasties (THAs) with a newest generation CC
      bearings to determine if these provide safe and well performing bearings. At the
      last follow-up, there were no cases of ceramic fracture or chipping and no
      revision surgery necessary for bearing related complication. One hip underwent
      two staged revision for infection and another underwent revision for dislocation,
      resulting in an overall 98.5% survival rate at a mean of 6 years. The newest
      generation of CC bearings provides a reliable and safe bearing in young, active
      patients undergoing THA.

PMID- 25869589
TI  - No Gender-Based Differences in Outcomes after Conventional Total Knee
      Arthroplasty in Asians.
AB  - PURPOSE: The purpose of this study is to evaluate the effect of gender on
      functional outcomes in Asian patients undergoing conventional total knee
      arthroplasty (TKA). PATIENTS AND METHODS: A review of 217 patients who underwent
      primary total knee arthroplasty by a single surgeon was conducted. Postoperative
      range of motion, Knee Society Score, Oxford Knee Score and Short Form-36 Physical
      Component Score (PCS) and Mental Component Score (MCS) were collected
      prospectively in all patients at both 6 months and 2 years following conventional
      TKA. The patients were then stratified based on gender and their outcomes were
      compared using Student's t-test. RESULTS: Preoperatively, the females had a
      significantly poorer flexion range as compared to the males. Postoperatively at 6
      months and 2 years following conventional TKA, both groups showed improvement
      from their preoperative range of motion and scores and had no significant
      differences in outcomes. CONCLUSION: Similar to several studies in the Western
      literature, gender does not seem to affect short-term outcomes in Asian patients
      undergoing TKA. Longer-term data on survivorship and outcomes are needed before
      routine use of gender-specific TKA can be recommended.

PMID- 25869590
TI  - Biochemical characterization of the roles of glycines 24 and 27 and threonine 179
      in tropomyosin from the fast skeletal trunk muscle of the atlantic salmon.
AB  - Atlantic salmon fast skeletal muscle is composed of an alpha-type tropomyosin
      that shares 20 substitutions with a mammalian homologue. Prominent isomorphisms
      considered to be potentially destabilizing include threonine 179 (core, Ala in
      rabbit) and a unique pair of glycines, residues 24 and 27. Bacterially expressed
      mutant tropomyosins were isolated without exposure to elevated temperature or
      organic solvent. The Thr179Ala mutant is more resistant to heat-induced
      denaturation (Tm > 40  degrees C) than the nonmutant control (Tm = 37  degrees C)
      as monitored by far-UV circular dichroism [0.1 M salt and 1 mM DTT (pH 7)].
      Changing one glycine to alanine has no detectable effect on the Tm versus the
      control value. An increase of 1  degrees C is observed for the double mutant
      (Gly27Ala/Gly24Ala). The preferred site of chymotryptic cleavage of recombinant
      salmon tropomyosin is between Leu 11 and Lys 12. The rate of the subsequent
      cleavage at Leu 169, the preferred site in rabbit tropomyosin, is reduced via
      replacement of Thr 179 with Ala. Thin filaments reconstituted with this mutant
      display greater Ca(II) induction of the myosin steady-state MgATPase versus
      control. Glycine-induced local instability is demonstrated by Escherichia coli
      outer membrane protease T (Omp-T) cleavage between Lys 6 and Lys 7. The control
      is more susceptible to proteolysis at this site than the mutants, which are
      distinct from each other: control > Gly27Ala > Gly24Ala > double mutant (most
      resistant to Omp-T). Similarly, the double mutant is comparatively more resistant
      to cleavage at Leu 11. By inference, the mid- and amino-terminal sections of
      salmon tropomyosin are intrinsically less stable than those in mammals,
      suggesting greater flexibility. Neighboring glycines make up a new
      destabilization motif in tropomyosin.

PMID- 25869591
TI  - Synthesis and Anticancer Activity of 4beta-Triazole-podophyllotoxin Glycosides.
AB  - A series of novel 4beta-triazole-podophyllotoxin glycosides were synthesized by
      utilizing the Click reaction. Evaluation of cytotoxicity against a panel of five
      human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7, SW480) using MTT assay
      shows that most of these compounds show weak cytotoxicity. It was observed that
      compound 16 shows the highest activity with IC50 values ranging from 2.85 to 7.28
      MUM, which is more potent than the control drugs etoposide and cisplatin against
      four of five cancer cell lines tested. Compound 16 is characterized with an alpha
      D-galactosyl residue directly linked to the triazole ring and a 4'-OH group on
      the E ring of the podophyllotoxin scaffold. HPLC investigation of representative
      compound indicates that incorporation of a sugar moiety seems to improve the
      chemical stability of the podophyllotoxin scaffold.

PMID- 25869592
TI  - Therapist correlates of attitudes toward sexual minority individuals, affirmative
      counseling self-efficacy, and beliefs about affirmative practice.
AB  - OBJECTIVE: The purpose of this study was to examine the influence of training in
      sexual minority issues, professional identification, and gender on attitudes
      toward lesbian, gay, and bisexual individuals, affirmative counseling self
      efficacy, and beliefs about affirmative practice among mental health
      practitioners in the USA. METHOD: We used the Internet to recruit a nationwide
      sample of 443 heterosexual psychologists (n = 270), clinical social workers (n =
      110), and marriage and family therapists (n = 63) residing in the USA. RESULTS:
      When controlling for years of practice experience and age, results from
      structural equation modeling analysis showed that training was associated with
      more affirmative attitudes, higher levels of affirmative counseling self
      efficacy, and more positive beliefs. Female therapists reported more affirmative
      attitudes and higher levels of affirmative counseling self-efficacy than male
      therapists. Professional identification did not predict any criterion variables,
      when controlling for years of practice experience and age. CONCLUSION: Findings
      suggest that it will be important for educational and training initiatives to
      consider the effect of gender role socialization on attitudes and affirmative
      counseling self-efficacy, especially among beginning male therapists.

PMID- 25869593
TI  - Extract from Phyllanthus urinaria L. inhibits hepatitis B virus replication and
      expression in hepatitis B virus transfection model in vitro.
AB  - OBJECTIVE: To explore the effects of the extract from Phyllanthus urinaria L. on
      hepatitis B virus (HBV) replication and expression in HBV transient transfection
      model in vitro. METHODS: The eukaryotic expression plasmid pHBV1.1, which
      contains 1.1-fold-overlength genome of HBV, was transfected into the human
      hepatoma cell line, HepG2, to establish and assess the HBV transient transfection
      model. The extract from Phyllanthus urinaria L. was prepared in different
      concentrations and methyl thiazolyl tetrazolium was used to detect the maximum
      nontoxic concentration of the drug. The extract from Phyllanthus urinaria L. were
      added into the transfected cell, at the concentrations of 0.8, 0.2 and 0.05 g/L,
      respectively. Four days after drug application, enzyme-linked immuno sorbent
      assay was used to detect the concentration of HBsAg in the supernatants, Southern
      blot was applied to analyze HBV DNA level, and Western blot was used to detect
      the expression of HBcAg in cells. RESULTS: After the transfection of plasmid
      pHBV1.1 into HepG2 cells, the concentration of HBsAg in supernatants was
      increased obviously as compared with that of the normal cells (P<0.05), and all
      expected HBV replicative intermediates were confirmed by Southern blot analysis,
      which ensured the successful establishment of the HBV transient transfection
      model. After the application of drugs at the concentrations of 0.8 and 0.2 g/L,
      the level of HBsAg was obviously decreased in the supernatants, as compared with
      that of the virus group (P<0.05); Southern blot showed that the level of HBV rc
      DNA, ds DNA, ss DNA was obviously reduced compared with that of the virus group
      (P<0.01); Western blot revealed that the expression of HBcAg in the drug group
      was obviously inhibited, as compared with that of the virus group (P<0.01).
      CONCLUSIONS: The extract from Phyllanthus urinaria L. obviously inhibited
      replication and expression of HBV in HBV transfected cell lines in vitro, thus
      exerting distinctive anti-HBV effects.

PMID- 25869594
TI  - Cocoa procyanidins with different degrees of polymerization possess distinct
      activities in models of colonic inflammation.
AB  - Procyanidins are available in the diet from sources such as cocoa and grapes.
      Procyanidins are unique in that they are comprised of repeating monomeric units
      and can exist in various degrees of polymerization. The degree of polymerization
      plays a role in determining the biological activities of procyanidins. However,
      generalizations cannot be made regarding the correlation between procyanidin
      structure and bioactivity because the size-activity relationship appears to be
      system dependent. Our aim was to screen fractions of procyanidins with differing
      degrees of polymerization in vitro for anti-inflammatory activities in models of
      colonic inflammation. Monomeric, oligomeric and polymeric cocoa procyanidin
      fractions were screened using cell models of disrupted membrane integrity and
      inflammation in human colon cells. High-molecular-weight polymeric procyanidins
      were the most effective at preserving membrane integrity and reducing secretion
      of interleukin-8 in response to inflammatory stimuli. Conversely, oligomeric
      procyanidins appeared to be the least effective. These results suggest that
      polymeric cocoa procyanidins may be the most effective for preventing loss of gut
      barrier function and epithelial inflammation, which are critical steps in the
      pathogenesis of metabolic endotoxemia, inflammatory bowel disease and colon
      cancer. Therefore, further investigations of the potential health-protective
      benefits of cocoa procyanidins with distinct degrees of polymerization,
      particularly high-molecular-weight procyanidins, are warranted. 

PMID- 25869595
TI  - Lycopene abrogates Abeta(1-42)-mediated neuroinflammatory cascade in an
      experimental model of Alzheimer's disease.
AB  - BACKGROUND: Neuroinflammation characterized by glial activation and release of
      proinflammatory mediators is considered to play a critical role in the
      pathogenesis of Alzheimer's disease (AD). beta-Amyloid1-42 (Abeta1-42)-induced
      learning and memory impairment in rats is believed to be associated with neuronal
      inflammation. OBJECTIVES: The present study was designed to investigate the
      effect of lycopene, a potent antioxidant and anti-inflammatory carotenoid, in
      intracerebroventricular (i.c.v.) Abeta1-42-induced neuroinflammatory cascade
      along with learning and memory impairment in rats. MATERIAL AND METHODS: I.c.v.
      Abeta1-42 was injected bilaterally followed by treatment with lycopene or
      rivastigmine for 14 days. Morris water maze and elevated plus maze tests were
      used to assess the memory function. Rats were sacrificed and brains harvested to
      evaluate various biochemical parameters and mitochondrial complex activities in
      postmitochondrial supernatant fractions of cerebral cortex and hippocampus of rat
      brains. The levels of tumor necrosis factor alpha (TNF-alpha), interleukin 1beta
      (IL-1beta), tumor growth factor beta (TGF-beta), nuclear factor-kappaB (NF
      kappaB) and caspase-3 were assessed by enzyme-linked immunosorbent assay
      analysis. RESULTS: Lycopene remediated Abeta-induced learning and memory deficits
      in a dose-dependent manner. Abeta1-42-induced mitochondrial dysfunction along
      with surge of proinflammatory cytokines TNF-alpha, TGF-beta and IL-1beta as well
      as NF-kappaB and caspase-3 activity in rat brain was significantly reduced with
      lycopene treatment. CONCLUSION: The amelioration of Abeta1-42-induced spatial
      learning and memory impairment by lycopene could be linked, at least in part, to
      the inhibition of NF-kappaB activity and the down-regulation of expression of
      neuroinflammatory cytokines, suggesting that lycopene may be a potential
      candidate for AD treatment.

PMID- 25869596
TI  - Ginkgolide B Protects Neurons from Ischemic Injury by Inhibiting the Expression
      of RTP801.
AB  - RTP801 (also known as REDD1), a stress-related protein, is induced by several
      environmental stresses such as ischemia and cigarette smoke. Although ischemia
      can dramatically up-regulate RTP801 expression in brain ischemia, up to now, the
      exact relation between RTP801 and neuronal death in ischemia is poorly
      understood. In the current study, using oxygen and glucose deprivation as an in
      vitro ischemic model in primary cultured cortical neurons, we found that the
      expression of RTP801 increased progressively with prolongation of ischemic
      duration, in which the expression of RTP801 is positively correlated with the
      release of lactate dehydrogenase (LDH) in neurons, and knockdown of RTP801
      promoted neuronal survival in ischemia-reperfusion. It was further found that
      ginkgolide B (GB) could significantly increase cell viability and decrease LDH
      release, and at the same time reduce the levels of RTP801 mRNA and protein in
      neurons after ischemia and reperfusion. Moreover, GB-induced reduction in
      expression of RTP801 was blocked by application of LY294002, a specific inhibitor
      of phosphatidylinositol 3-kinase (PI3K). These results demonstrate that RTP801
      could play a detrimental role on neurons in ischemia, and GB might protect
      neurons against ischemic injury by inhibiting RTP801 expression via PI3K pathway.

PMID- 25869597
TI  - Improvements in the data quality of a national BMI measuring programme.
AB  - Variations in data collection between collecting regions can affect the outcome
      measures. This study examines the impact of improvements in data collection on
      outcome measures in a national monitoring programme between 2007/2008 and
      2010/2011. Multilevel analysis of 2007/2008 and 2010/2011 National Child
      Measurement Programme (NCMP) data estimated the relationship between body mass
      index (BMI) z-score and data collection variations within coordinating regions,
      while adjusting for individual-level and school-level factors. The total sample
      was 2,013,285 students from 17,279 primary schools in 152 coordinating regions in
      England. Data collection differences accounted for 31.2% of the regional
      variation in BMI z-score for Reception (aged 4-5 years) students in 2007/2008;
      this reduced to 12.6% in 2010/2011. For Year 6 (aged 10-11 years) students, it
      reduced from 5.3% in 2007/2008 to 2.4% in 2010/2011. Digit preference in the
      rounding of weight measurements showed the largest decreases, from 27.3 to 4.5%
      for Reception year pupils and from 4.2 to 1.0% for Year 6 pupils. This
      demonstrates that improvements in data collection variation between regions in
      the NCMP have led to improvements in data quality.

PMID- 25869598
TI  - Comparison of anthropometric measurements in children to predict metabolic
      syndrome in adolescence: analysis of prospective cohort data.
AB  - OBJECTIVES: The optimal screening measures for obesity in children remain
      controversial. Our study aimed to determine the anthropometric measurement at age
      10 years that most strongly predicts the incidence of cardio-metabolic risk
      factors at age 13 years. SUBJECTS/METHODS: This was a prospective cohort study of
      a population-based cohort of 438 children followed between age 7 and 13 years of
      age. The main exposure variables were adiposity at age 10 years determined from
      body mass index (BMI) Z-score, waist circumference (WC) Z-score, waist-to-hip
      ratio and waist-to-height ratio. Outcome measures included systolic (SBP) and
      diastolic blood pressure (DBP), fasting high-density (HDL-c) and low-density
      lipoprotein cholesterol (LDL-c), triglycerides, insulin and glucose (homeostasis
      model of assessment, HOMA), and the presence of metabolic syndrome (MetS).
      RESULTS: WC Z-score at age 10 years was a stronger predictor of SBP (beta 0.21,
      R(2) 0.38, P<0.001 vs beta 0.30, R(2) 0.20, P<0.001) and HOMA (beta 0.51, R(2)
      0.25, P<0.001 vs 0.40, R(2) 0.19, P<0.001) at age 13 years compared with BMI Z
      score. WC relative to height and hip was stronger predictors of cardio- metabolic
      risk than BMI Z-score or WC Z-score. The relative risk (RR) of incident MetS was
      greater for an elevated BMI Z-score than for an elevated WC (girls: RR 2.52, 95%
      confidence interval (CI): 1.46-4.34 vs RR 1.56, 95% CI 1.18-2.07) and (boys: RR
      2.86, 95% CI 1.79-4.62 vs RR 2.09, 95% CI 1.59-2.77). CONCLUSIONS: WC was a
      better predictor of SBP and HOMA compared with BMI or WC expressed relative to
      height or hip circumference. BMI was associated with higher odds of MetS compared
      with WC. Thus, BMI and WC may each be clinically relevant markers of different
      cardio-metabolic risk factors, and important in informing obesity-related
      prevention and treatment strategies.

PMID- 25869599
TI  - Metabolic effects of bariatric surgery in mouse models of circadian disruption.
AB  - BACKGROUND/OBJECTIVES: Mounting evidence supports a link between circadian
      disruption and metabolic disease. Humans with circadian disruption (for example,
      night-shift workers) have an increased risk of obesity and cardiometabolic
      diseases compared with the non-disrupted population. However, it is unclear
      whether the obesity and obesity-related disorders associated with circadian
      disruption respond to therapeutic treatments as well as individuals with other
      types of obesity. SUBJECTS/METHODS: Here, we test the effectiveness of the
      commonly used bariatric surgical procedure, Vertical Sleeve Gastrectomy (VSG), in
      mouse models of genetic and environmental circadian disruption. RESULTS: VSG led
      to a reduction in body weight and fat mass in both Clock(Delta19) mutant and
      constant-light mouse models (P<0.05), resulting in an overall metabolic
      improvement independent of circadian disruption. Interestingly, the decrease in
      body weight occurred without altering diurnal feeding or activity patterns
      (P>0.05). Within circadian-disrupted models, VSG also led to improved glucose
      tolerance and lipid handling (P<0.05). CONCLUSIONS: Together these data
      demonstrate that VSG is an effective treatment for the obesity associated with
      circadian disruption, and that the potent effects of bariatric surgery are
      orthogonal to circadian biology. However, as the effects of bariatric surgery are
      independent of circadian disruption, VSG cannot be considered a cure for
      circadian disruption. These data have important implications for circadian
      disrupted obese patients. Moreover, these results reveal new information about
      the metabolic pathways governing the effects of bariatric surgery as well as of
      circadian disruption.

PMID- 25869600
TI  - Personal and social norms for food portion sizes in lean and obese adults.
AB  - BACKGROUND: Portion size is an important component of dietary advice for weight
      control, but little is known about what portion sizes people consider 'normal'.
      This study determined the effect of body mass index (BMI), gender, dietary
      restraint and liking of the food on personal and social portion size norms for a
      range of foods and the degree of certainty over the norms. METHODS: Thirty lean
      (BMI 20-25 kg m(-)(2)) and 30 obese (BMI 30-35 kg m(-)(2)) men and women (aged 18
      60 years) viewed 17 different portion sizes of 12 foods on a computer screen on
      two occasions a week apart. Participants responded 'more' or 'less' to each
      photograph reflecting personal portion size preference or perceived portion sizes
      of others. Personal and social norms for portion sizes of each food were
      determined using the method of constant stimuli giving a sigmoidal curve of the
      probability of answering 'less' over a range of portion sizes. The slope of the
      sigmoid at the norm gave a measure of certainty about the norm. Regression models
      were used to examine the effect of BMI, gender, dietary restraint and liking of
      the food on personal norms, social norms, the relationship between norms, and the
      slopes. RESULTS: Personal norms were significantly larger in the obese (P=0.026),
      men (P<0.001), those with lower dietary restraint (P<0.001), and those with
      higher liking for the food (P<0.001). Social norms were larger for women
      (P=0.012). The slopes at the norms were 30% shallower in the obese and in men
      (P<0.001). CONCLUSION: Larger personal norms for portion size among the obese,
      men, those with lower dietary restraint and those with higher liking for a food
      imply greater consumption, which may undermine weight control. Shallower slopes
      for norms in the obese and in men may imply less clearly defined habitual portion
      sizes.

PMID- 25869601
TI  - Blocking high-fat diet-induced obesity, insulin resistance and fatty liver by
      overexpression of Il-13 gene in mice.
AB  - OBJECTIVES: The objective of this study was to assess the activity of anti
      inflammatory cytokine IL-13 (interleukin-13) in blocking high-fat diet-induced
      obesity and obesity-associated insulin resistance and liver steatosis. METHODS:
      C57BL/6 mice were fed a high-fat diet and received hydrodynamic delivery of
      plasmids carrying the mouse Il-13 or Gfp (control) gene. IL-13 blood protein
      levels, food consumption and body weight of mice were continuously monitored for
      8 weeks. Fat and lean masses of treated and control animals were determined at
      the end of the experiment. Serum concentrations of glucose, insulin and lipids
      were determined, and mRNA levels of macrophage marker genes in adipose tissue and
      genes involved in energy metabolism were examined using real-time PCR. Glucose
      tolerance and insulin sensitivity tests were performed to determine glucose
      homeostasis. Histochemistry and lipid assays were performed to determine the
      hepatic lipid accumulation. RESULTS: Blood concentration of IL-13 was 20 ng ml(
      1) 1 week after gene delivery and declined with time. Overexpression of Il-13
      prevented high-fat diet-induced weight gain without affecting food consumption.
      Mice that underwent Il-13 gene transfer showed regular body weight and normal
      serum concentrations of glucose and insulin, and less lipid accumulation in the
      liver. Overexpression of Il-13 blocked macrophage infiltration in adipose tissue
      and suppressed high-fat diet-induced expression of inflammatory F4/80, Cd68 and
      Mcp1, and elevated the expression of Ucp1 (uncoupling protein 1 gene) responsible
      for energy expenditure. CONCLUSION: These results suggest that suppression of
      diet-induced inflammation by IL-13 is an effective strategy in preventing diet
      induced obesity and obesity-associated insulin resistance and fatty liver.

PMID- 25869602
TI  - Three-year weight change and cardiometabolic risk factors in obese and normal
      weight adults who are metabolically healthy: the atherosclerosis risk in
      communities study.
AB  - BACKGROUND/OBJECTIVES: Approximately 17% of obese Americans are free of the
      cardiometabolic risk factors, but few studies have compared responses to weight
      change in metabolically healthy obese (MHO) and metabolically healthy normal
      weight (MHNW) adults. We compared the impact of weight loss, weight maintenance
      and weight gain on cardiometabolic risk factors in the MHO and the MHNW.
      SUBJECTS/METHODS: Data were from the Atherosclerosis Risk in Communities (ARIC)
      study. Multiple observations on 2710 participants were included, yielding 4541
      observations of sequential 3-year intervals. Metabolically healthy was defined as
      absence of all components of metabolic syndrome excluding waist circumference.
      Mixed effects models were used to compare changes in each of five cardiometabolic
      risk factors within weight change categories (<-3% for weight loss, +/-3% for
      weight maintenance and >3% for weight gain). RESULTS: Weight loss was associated
      with comparable small changes or no changes in cardiometabolic risk factors in
      MHO and MHNW individuals. Weight gain was associated with larger increases in
      systolic (8.6 vs 6.2 mm Hg) and diastolic (3.9 vs 2.5 mm Hg) blood pressure,
      triglycerides (21.9 vs 15.8 mg/dl) and glucose (4.9 vs 1.9 mg/dl) in MHO
      individuals compared with MHNW individuals. Weight maintenance was associated
      with larger increases in triglycerides (10.0 vs 6.4 mg/dl) and glucose (1.7 vs
      0.9 mg/dl) in MHO compared with MHNW individuals. MHO weight losers had more
      favorable changes in the five cardiometabolic risk factors compared to MHO weight
      maintainers (P<0.02) or gainers (P<0.0001). CONCLUSIONS: This work showed
      differences between MHNW and MHO adults and supports recommendations for weight
      loss in the MHO in order to avoid increases in risk factors associated with
      weight maintenance and weight gain.

PMID- 25869603
TI  - Inhibitory control in otherwise healthy overweight 10-year-old children.
AB  - BACKGROUND: Preventing obesity is a worldwide public health priority. In
      vulnerable children living in obesogenic environments, with easy access to high
      caloric food, alterations in inhibitory control functions might favor excessive
      food intake and affect energy regulation. We hypothesized that overweight/obese
      children would present lower inhibitory control in comparison to normal weight
      children. METHODS: We measured inhibitory control functions in 93 otherwise
      healthy overweight/obese and 92 normal weight 10-year-old children using the
      Stroop test and the Go/No-Go task. Event-related potentials were recorded during
      the Go/No-Go task. RESULTS: Overweight/obese children showed slower reaction
      times (1248.6 ms (95% confidence interval (CI): 1182.9-1314.3) vs 1149.0 ms (95%
      CI: 1083.0-1215.1)) on the Stroop test, higher reaction time variability (0.25
      (95% CI: 0.22-0.27) vs 0.21 (95% CI: 0.19-0.24)) on the Go/No-Go task and
      decreased P300 amplitude (4.1 MUV (95% CI: 3.0-5.2) vs 6.4 MUV (95% CI: 5.2-7.6))
      on event-related potentials compared with normal weight children. CONCLUSIONS:
      Our results indicate altered inhibitory control functions in otherwise healthy
      overweight/obese children, which might contribute to their excessive food
      consumption.

PMID- 25869604
TI  - Age-specific changes in BMI and BMI distribution among Australian adults using
      cross-sectional surveys from 1980 to 2008.
AB  - BACKGROUND: Research efforts have focused mainly on trends in obesity among
      populations, or changes in mean body mass index (BMI), without consideration of
      changes in BMI across the BMI spectrum. Examination of age-specific changes in
      BMI distribution may reveal patterns that are relevant to targeting of
      interventions. METHODS: Using a synthetic cohort approach (which matches members
      of cross-sectional surveys by birth year) we estimated population representative
      annual BMI change across two time periods (1980 to 1989 and 1995 to 2008) by age,
      sex, socioeconomic position and quantiles of BMI. Our study population was a
      total of 27349 participants from four nationally representative Australian health
      surveys; Risk Factor Prevalence Study surveys (1980 and 1989), the 1995 National
      Nutrition Survey and the 2007/8 National Health Survey. RESULTS: We found greater
      mean BMI increases in younger people, in those already overweight and in those
      with lower education. For men, age-specific mean annual BMI change was very
      similar in the 1980s and the early 2000s (P=0.39), but there was a recent slowing
      down of annual BMI gain for older women in the 2000s compared with their same-age
      counterparts in the 1980s (P<0.05). BMI change was not uniform across the BMI
      distribution, with different patterns by age and sex in different periods. Young
      adults had much greater BMI gain at higher BMI quantiles, thus adding to the
      increased right skew in BMI, whereas BMI gain for older populations was more even
      across the BMI distribution. CONCLUSIONS: The synthetic cohort technique provided
      useful information from serial cross-sectional survey data. The quantification of
      annual BMI change has contributed to an understanding of the epidemiology of
      obesity progression and identified key target groups for policy attention-young
      adults, those who are already overweight and those of lower socioeconomic status.

PMID- 25869605
TI  - High sodium intake is associated with short leukocyte telomere length in
      overweight and obese adolescents.
AB  - BACKGROUND/OBJECTIVES: Telomere shortening has an important role in cellular
      aging. However, the impact of high sodium intake, an important risk factor of age
      related diseases, on telomere shortening remains unknown. Therefore, we examined
      the relationship between high dietary sodium intake and leukocyte telomere length
      (LTL), particularly in the context of obesity, as obesity increases salt
      sensitivity. SUBJECTS/METHODS: LTL was determined by a quantitative polymerase
      chain reaction method in 766 adolescents aged 14-18 years (50% females, 49%
      African Americans). Dietary sodium intake was assessed by seven independent 24-h
      dietary recalls. We divided the sample into low sodium (mean 2388+/-522 mg per
      day) or high sodium groups (mean 4142+/-882 mg per day) based on the median value
      (3280.9 mg per day). RESULTS: In the entire cohort, there was no significant
      association between sodium intake and LTL (r=-0.05, P=0.24). However, there was a
      significant interaction between sodium intake and obesity status (P=0.049).
      Further multiple linear regression analyses revealed that higher dietary sodium
      intake was associated with shorter LTL in the overweight/obese group (body mass
      index ?85th percentile, beta=-0.37, P=0.04), but not in the normal-weight group
      (beta=0.01, P=0.93) after adjusting for multiple confounding factors. In the
      overweight/obese group, LTL was significantly shorter in the high sodium intake
      subjects vs low sodium intake subjects (1.24+/-0.22 vs. 1.32+/-0.20, P=0.02), but
      not the normal-weight group (1.29+/-0.24 vs 1.30+/-0.24, P=0.69). CONCLUSIONS:
      Higher dietary sodium intake is associated with shorter telomere length in
      overweight and obese adolescents.

PMID- 25869606
TI  - Human supraphysiological gestational weight gain and fetoplacental vascular
      dysfunction.
AB  - OBJECTIVE: Human foetal development and growth in an environment of maternal
      obesity associates with high risk of cardiovascular disease and adverse neonatal
      outcome. We studied whether supraphysiological gestational weight gain results in
      human fetoplacental endothelial dysfunction and altered fetoplacental vascular
      reactivity. METHODS: Primary cultures of human umbilical vein endothelial cells
      (HUVECs) and umbilical vein rings were obtained from pregnant women (112 total of
      patients recruited, 7 patients dropped out) exhibiting prepregnancy normal weight
      that ended with a physiological (pGWG (n=67), total weight gain 11.5-16 kg, rates
      of weight gain <=0.42 kg per week) or supraphysiological (spGWG (n=38), total
      weight gain >16 kg, rates of weight gain >0.42 kg per week) gestational weight
      gain (reference values from US Institute of Medicine guidelines). Vascular
      reactivity to insulin (0.1-1000 nmol l(-1), 5 min) in KCl-preconstricted vein
      rings was measured using a wire myograph. Protein levels of human equilibrative
      nucleoside transporter 1 (hENT1), total and Ser(1177)- or Thr(495)-phosphorylated
      endothelial nitric oxide synthase (eNOS) were detected by western blot or
      immunofluorescence, and adenosine transport (0-250 MUmol l(-1) adenosine, 2 MUCi
      ml(-1) [(3)H]adenosine, 20 s, 25  degrees C) was measured in the presence or
      absence of 1 MUmol l(-1) nitrobenzylthioinosine (hENT1 inhibitor) or 10 MUmol l(
      1) chlorpromazine (CPZ, endocytosis inhibitor) in HUVECs. RESULTS: spGWG
      associates with reduced NOS activity-dependent dilation of vein rings (P=0.001),
      lower eNOS expression and higher Thr(495) (P=0.044), but unaltered Ser(1177)eNOS
      phosphorylation. hENT1-adenosine maximal transport activity was reduced
      (P=0.041), but the expression was increased (P=0.001) in HUVECs from this group.
      CPZ increased hENT1-adenosine transport (P=0.040) and hENT1 plasma membrane
      accumulation only in cells from pGWG. CONCLUSION: spGWG in women with a normal
      prepregnancy weight causes lower fetoplacental vascular reactivity owing to the
      downregulation of eNOS activity and adenosine transport in HUVECs. Maternal spGWG
      is a detrimental condition for human fetoplacental endothelial function and
      reducing these alterations could result in a better neonate outcome.

PMID- 25869607
TI  - Low cytochrome oxidase 4I1 links mitochondrial dysfunction to obesity and type 2
      diabetes in humans and mice.
AB  - OBJECTIVES: Cytochrome oxidase (COX) dysfunction is associated with mitochondrial
      oxidative stress. We determined the association between COX expression, obesity
      and type 2 diabetes. SUBJECTS/METHODS: COX4I1 and COX10 genes were measured in
      monocytes of 24 lean controls, 31 glucose-tolerant and 67 diabetic obese
      patients, and 17 morbidly obese patients before and after bariatric surgery. We
      investigated the effect of caloric restriction and peroxisome proliferator
      activated receptor (PPAR) agonist treatment on Cox in obese diabetic mice, and
      that of diet-induced insulin resistance in Streptozotocin-treated mice. RESULTS:
      Low COX4I1 was associated with type 2 diabetes in obese patients, adjusting for
      age, gender, smoking, interleukin-6 and high-sensitivity C-reactive protein, all
      related to metabolic syndrome (MetS; odds ratio: 6.1, 95% confidence interval:
      2.3-16). In contrast, COX10 was low in glucose-tolerant and diabetic obese
      patients. In morbidly obese patients, COX4I1 was lower in visceral adipose tissue
      collected at bariatric surgery. In their monocytes, COX4I1 decreased after
      bariatric surgery, and low COX4I1 at 4 months was associated with MetS at 7
      years. In leptin-deficient obese diabetic mice, Cox4i1 was low in white visceral
      adipose tissue (n=13; P<0.001) compared with age-matched lean mice (n=10).
      PPARgamma-agonist treatment (n=13), but not caloric restriction (n=11), increased
      Cox4i1 (P<0.001). Increase in Cox4i1 depended on the increase in glucose
      transporter 4 (Glut4) expression and insulin sensitivity, independent of the
      increase in blood adiponectin. In streptozotocin-treated mice (three groups of
      seven mice, diet-induced insulin resistance decreased Cox4i1 and Glut4 (P<0.001
      for both). CONCLUSION: COX4I1 depression is related to insulin resistance and
      type 2 diabetes in obesity. In peripheral blood monocytes, it may be a
      diagnostically useful biomarker.

PMID- 25869608
TI  - Psychosocial factors and obesity in 17 high-, middle- and low-income countries:
      the Prospective Urban Rural Epidemiologic study.
AB  - BACKGROUND/OBJECTIVES: Psychosocial stress has been proposed to contribute to
      obesity, particularly abdominal, or central obesity, through chronic activation
      of the neuroendocrine systems. However, these putative relationships are complex
      and dependent on country and cultural context. We investigated the association
      between psychosocial factors and general and abdominal obesity in the Prospective
      Urban Rural Epidemiologic study. SUBJECTS/METHODS: This observational, cross
      sectional study enrolled 151 966 individuals aged 35-70 years from 628 urban and
      rural communities in 17 high-, middle- and low-income countries. Data were
      collected for 125 290 individuals regarding education, anthropometrics,
      hypertension/diabetes, tobacco/alcohol use, diet and psychosocial factors (self
      perceived stress and depression). RESULTS: After standardization for age, sex,
      country income and urban/rural location, the proportion with obesity (body mass
      index >=30 kg m(-)(2)) increased from 15.7% in 40 831 individuals with no stress
      to 20.5% in 7720 individuals with permanent stress, with corresponding
      proportions for ethnicity- and sex-specific central obesity of 48.6% and 53.5%,
      respectively (P<0.0001 for both). Associations between stress and
      hypertension/diabetes tended to be inverse. Estimating the total effect of
      permanent stress with age, sex, physical activity, education and region as
      confounders, no relationship between stress and obesity persisted (adjusted
      prevalence ratio (PR) for obesity 1.04 (95% confidence interval: 0.99-1.10)).
      There was no relationship between ethnicity- and sex-specific central obesity
      (adjusted PR 1.00 (0.97-1.02)). Stratification by region yielded inconsistent
      associations. Depression was weakly but independently linked to obesity (PR 1.08
      (1.04-1.12)), and very marginally to abdominal obesity (PR 1.01 (1.00-1.03)).
      CONCLUSIONS: Although individuals with permanent stress tended to be slightly
      more obese, there was no overall independent effect and no evidence that
      abdominal obesity or its consequences (hypertension, diabetes) increased with
      higher levels of stress or depression. This study does not support a causal link
      between psychosocial factors and abdominal obesity.

PMID- 25869609
TI  - IL-35 inhibits HBV antigen-specific IFN-gamma-producing CTLs in vitro.
AB  - Interleukin (IL)-35 is an inhibitory cytokine consisting of IL-12A and Epstein
      Barr virus-induced gene 3 (Ebi3) and is required by regulatory T-cells (Tregs)
      for maximal activity. During chronic hepatitis B virus (HBV) infection, Tregs
      have immunosuppressive effects on HBV-specific T helper (Th) cells, yet little is
      known about the complex regulation of Tregs and their contribution to the
      inadequate immune system response to the virus. In the present study, we
      investigated whether IL-35 is involved in HBV-related cellular immune responses.
      Cluster of differentiation (CD)4(+) T-cells from peripheral blood were derived
      from healthy volunteers, resolved HBV individuals and chronic active hepatitis B
      patients and stimulated with CD3/28-conjugated beads. We analysed mRNA and
      protein levels of IL-35 and assessed the inhibitory effect of IL-35 on HBV core
      antigen-specific cytotoxic T lymphocytes (CTLs), dendritic cells (DCs) and
      effector T-cells (Teffs). Correlation analyses between liver inflammation and HBV
      DNA load were conducted. Results show that chronic HBV patients harbour
      significantly higher levels of Ebi3 mRNA and protein in CD4(+) T-cells compared
      with healthy volunteers and resolved HBV individuals. IL-35 suppressed the
      proliferation of HBV antigen-specific CTLs and interferon (IFN)-gamma production
      in vitro. Ex vivo, IL-35 decreased the proliferation of CD4(+)CD45RA(+) naive T
      cells, especially in CD4(+)CD25(-)CD45RA(+) naive Teffs. IL-35 inhibited the
      expansion of CD11c(+) DCs. Our data indicate that IL-35 is highly expressed in
      chronic HBV CD4(+) T-cells and plays an important role in the inhibition of the
      cellular immune response in chronic HBV. 

PMID- 25869610
TI  - Amyloid-beta Activates Microglia and Regulates Protein Expression in a Manner
      Similar to Prions.
AB  - Prions are the only convincingly demonstrated proteinaceous infectious particle,
      yet recent studies find that amyloid-beta peptide (Abeta) aggregates are capable
      of self-propagation, which induces amyloidosis pathology in Alzheimer's disease
      (AD) model mice that is similar to the self-propagation phenomenon of prions in
      neurons. Gliosis is a common hallmark of AD and prion diseases, in which
      activated microglia accumulate around abnormal protein deposits. Analyses of the
      characteristics of activated microglia induced by Abeta in comparison with those
      induced by prions will provide new insight into the pathogenesis of AD.
      Therefore, we compared the characteristics of BV-2 cells (model microglia)
      activated by Abeta fibrillar peptides (Abeta1-42) and prions (PrP106-126). Abeta1
      42 and PrP106-126, as well as the supernatants of the media collected from BV-2
      cells cocultured with Abeta1-42 and PrP106-126, were potent activators of BV-2
      microglial activity, but the chemotaxis index (CI) induced by Abeta1-42 was
      significantly higher than that induced by PrP106-126 at each concentration.
      Abeta1-42 and PrP106-126 increased the proliferation index (PI) and upregulated
      monocyte chemoattractant protein-1 (MCP-1) and transforming growth factor beta 1
      (TGF-beta1) expression after 12 h of exposure. Our results show that Abeta
      activates microglia and regulates microglial protein expression in a manner
      similar to prions and, thus, provide new insight into the pathogenesis of AD.

PMID- 25869611
TI  - A Novel MGC4607/CCM2 Gene Mutation Associated with Cerebral Spinal and Cutaneous
      Cavernous Angiomas.
AB  - Cerebral cavernous malformations (CCMs) are vascular abnormalities that may cause
      seizures, headaches, intracerebral hemorrhages, and focal neurological deficits;
      they can also be clinically silent and occur as a sporadic or an autosomal
      dominant condition. Three genes have been identified as causing familial CCM:
      KRIT1/CCM1, MGC4607/CCM2, and PDCD10/CCM3, mapping, respectively, on chromosomes
      7q, 7p, and 3q. Here, we report an Italian family affected by CCM due to a
      MGC4607 gene mutation, on exon 4. All the affected subjects suffered from
      seizures, and some of them underwent surgery for removal of a cavernous angioma.
      Brain MRI showed multiple lesions consistent with CCMs in all patients. Spinal
      and cutaneous cavernous angiomas were present too. This report underlines the
      need for a careful interdisciplinarity among neurologists, neuroradiologists,
      neurosurgeons, geneticists, ophthalmologists, and dermatologists for a total
      evaluation of the different manifestations of familial CCM. This points out that
      only referral centers are organized to offer a multidisciplinary management of
      this disease. 

PMID- 25869612
TI  - Improving Significance in Association Studies: a New Perspective for Association
      Studies Submitted to the Journal of Molecular Neuroscience.

PMID- 25869613
TI  - Pygo2 siRNA Inhibit the Growth and Increase Apoptosis of U251 Cell by Suppressing
      Histone H3K4 Trimethylation.
AB  - The development of novel therapeutic strategies for glioma requires the
      identification of molecular targets involved in malignancy. Pygopus (Pygo) is a
      new discovered and specific downstream component of canonical Wnt signaling. Our
      previous study has demonstrated that Pygo2 is highly expressed in and promotes
      the growth of glioma cells. However, the role of Pygo2 in glioma remains to be
      elucidated. In the current study, we investigated the role of Pygo2 in human
      glioma U251 cells and showed that knocking down of the expression of Pygo2 in
      U251 cells using lentivirally expressed siRNA have inhibited cell proliferation
      and increased apoptosis through decreasing H3K4me3 expression. Moreover, we found
      Pygo2 was enriched in U251 glioma cancer stem-like cells and Pygo2 siRNA resulted
      in a reduced number as well as size of tumor spheres. According to our result,
      this paper now links mechanistically Pygo2's role in histone modification to its
      enhancement/reduction of proliferation/apoptosis in glioma cells and indicate
      that Pygo2 may play an important role in self-renew and proliferation in U251
      glioma cancer stem-like cells. 

PMID- 25869614
TI  - Carnosine decreases IGFBP1 production in db/db mice through suppression of HIF-1.
AB  - IGF binding protein 1 (IGFBP1) is a member of the binding proteins for the IGF
      with an important role in glucose homeostasis. Circulating IGFBP1 is derived
      essentially from the liver where it is mainly regulated negatively by insulin.
      Carnosine, a natural antioxidant, has been shown to improve metabolic control in
      different animal models of diabetes but its mechanisms of action are still not
      completely unraveled. We therefore investigate the effect of carnosine treatment
      on the IGFBP1 regulation in db/db mice. Db/db mice and heterozygous non-diabetic
      mice received for 4 weeks regular water or water supplemented with carnosine.
      Igfbp1 mRNA expression in the liver was evaluated using qPCR and the protein
      levels in plasma by western blot. Plasma IGF1 and insulin were analyzed using
      immunoassays. HepG2 cells were used to study the in vitro effect of carnosine on
      IGFBP1. The modulation of hypoxia inducible factor-1 alpha (HIF-1alpha) which is
      the central mediator of hypoxia-induction of IGFBP1 was analyzed using: WB,
      reporter gene assay and qPCR. Carnosine decreased the circulating IGFBP1 levels
      and the liver expression Igfbp1, through a complex mechanism acting both directly
      by suppressing the HIF-1alpha-mediated IGFBP1 induction and indirectly through
      increasing circulating insulin level followed by a decrease in the blood glucose
      levels and increased the plasma levels or IGF1. Reduction of IGFBP1 in diabetes
      through insulin-dependent and insulin-independent pathways is a novel mechanism
      by which carnosine contributes to the improvement of the metabolic control in
      diabetes. 

PMID- 25869615
TI  - Nesfatin-1 inhibits proliferation and enhances apoptosis of human adrenocortical
      H295R cells.
AB  - NUCB2/nesfatin and its proteolytically cleaved product nesfatin-1 are recently
      discovered anorexigenic hypothalamic neuroproteins involved in energy
      homeostasis. It is expressed both centrally and in peripheral tissues, and
      appears to have potent metabolic actions. NUCB2/nesfatin neurons are activated in
      response to stress. Central nesfatin-1 administration elevates circulating ACTH
      and corticosterone levels. Bilateral adrenalectomy increased NUCB2/nesfatin mRNA
      levels in rat paraventricular nuclei. To date, studies have not assessed the
      effects of nesfatin-1 stimulation on human adrenocortical cells. Therefore, we
      investigated the expression and effects of nesfatin-1 in a human adrenocortical
      cell model (H295R). Our findings demonstrate that NUCB2 and nesfatin-1 are
      expressed in human adrenal gland and human adrenocortical cells (H295R).
      Stimulation with nesfatin-1 inhibits the growth of H295R cells and promotes
      apoptosis, potentially via the involvement of Bax, BCL-XL and BCL-2 genes as well
      as ERK1/2, p38 and JNK1/2 signalling cascades. This has implications for
      understanding the role of NUCB2/nesfatin in adrenal zonal development.
      NUCB2/nesfatin may also be a therapeutic target for adrenal cancer. However,
      further studies using in vivo models are needed to clarify these concepts. 

PMID- 25869616
TI  - 11beta-HSD1 reduces metabolic efficacy and adiponectin synthesis in hypertrophic
      adipocytes.
AB  - Mitochondrial dysfunction in hypertrophic adipocytes can reduce adiponectin
      synthesis. We investigated whether 11beta-hydroxysteroid dehydrogenase type 1
      (11beta-HSD1) expression is increased in hypertrophic adipocytes and whether this
      is responsible for mitochondrial dysfunction and reduced adiponectin synthesis.
      Differentiated 3T3L1 adipocytes were cultured for up to 21 days. The effect of
      AZD6925, a selective 11beta-HSD1 inhibitor, on metabolism was examined. db/db
      mice were administered 600 mg/kg AZD6925 daily for 4 weeks via gastric lavage.
      Mitochondrial DNA (mtDNA) content, mRNA expression levels of 11 beta -H sd1 and
      mitochondrial biogenesis factors, adiponectin synthesis, fatty acid oxidation
      (FAO), oxygen consumption rate and glycolysis were measured. Adipocyte
      hypertrophy in 3T3L1 cells exposed to a long duration of culture was associated
      with increased 11 beta -Hsd1 mRNA expression and reduced mtDNA content,
      mitochondrial biogenesis factor expression and adiponectin synthesis. These cells
      displayed reduced mitochondrial respiration and increased glycolysis. Treatment
      of these cells with AZD6925 increased adiponectin synthesis and mitochondrial
      respiration. Inhibition of FAO by etomoxir blocked the AZD6925-induced increase
      in adiponectin synthesis, indicating that 11beta-HSD1-mediated reductions in FAO
      are responsible for the reduction in adiponectin synthesis. The expression level
      of 11 beta -Hsd1 was higher in adipose tissues of db/db mice. Administration of
      AZD6925 to db/db mice increased the plasma adiponectin level and adipose tissue
      FAO. In conclusion, increased 11beta-HSD1 expression contributes to reduced
      mitochondrial respiration and adiponectin synthesis in hypertrophic adipocytes.

PMID- 25869617
TI  - Effect of estrogen receptor-subtype-specific ligands on fertility in adult male
      rats.
AB  - Maintenance of normal male fertility relies on the process of spermatogenesis
      which is under complex endocrine control by mechanisms involving gonadotropin and
      steroid hormones. Although testosterone is the primary sex steroid in males,
      estrogen is locally produced in the testis and plays a very crucial role in male
      fertility. This is evident from presence of both the estrogen receptors alpha
      (ERalpha) and beta (ERbeta) in the testis and their absence, as in the case of
      knockout mice models, leads to sterility. The present study was undertaken to
      understand individual roles of the two ERs in spermatogenesis and their direct
      contribution towards the maintenance of male fertility using receptor-subtype
      specific ligands. Administration of ERalpha and beta agonists to adult male rats
      for 60 days results in a significant decrease in fertility, mainly due to an
      increase in pre- and post-implantation loss and a concomitant decrease in litter
      size and sperm counts. Our results indicate that ERalpha is mainly involved in
      negative feedback regulation of gonadotropin hormones, whereas both ERs are
      involved in regulation of prolactin and testosterone production. Histological
      examinations of the testis reveal that ERbeta could be involved in the process of
      spermiation since many failed spermatids were observed in stages IX-XI following
      ERbeta agonist treatment. Our results indicate that overactivation of estrogen
      signaling through either of its receptors can have detrimental effects on the
      fertility parameters and that the two ERs have both overlapping and distinct
      roles in maintenance of male fertility. 

PMID- 25869618
TI  - The Now-or-Never bottleneck: A fundamental constraint on language.
AB  - Memory is fleeting. New material rapidly obliterates previous material. How,
      then, can the brain deal successfully with the continual deluge of linguistic
      input? We argue that, to deal with this "Now-or-Never" bottleneck, the brain must
      compress and recode linguistic input as rapidly as possible. This observation has
      strong implications for the nature of language processing: (1) the language
      system must "eagerly" recode and compress linguistic input; (2) as the bottleneck
      recurs at each new representational level, the language system must build a
      multilevel linguistic representation; and (3) the language system must deploy all
      available information predictively to ensure that local linguistic ambiguities
      are dealt with "Right-First-Time"; once the original input is lost, there is no
      way for the language system to recover. This is "Chunk-and-Pass" processing.
      Similarly, language learning must also occur in the here and now, which implies
      that language acquisition is learning to process, rather than inducing, a
      grammar. Moreover, this perspective provides a cognitive foundation for
      grammaticalization and other aspects of language change. Chunk-and-Pass
      processing also helps explain a variety of core properties of language, including
      its multilevel representational structure and duality of patterning. This
      approach promises to create a direct relationship between psycholinguistics and
      linguistic theory. More generally, we outline a framework within which to
      integrate often disconnected inquiries into language processing, language
      acquisition, and language change and evolution.

PMID- 25869619
TI  - Accumulation and age-related elevation of amyloid-beta within basal forebrain
      cholinergic neurons in the rhesus monkey.
AB  - Basal forebrain cholinergic neurons (BFCN) are selectively vulnerable to damage
      and loss in a number of neurodegenerative disorders that afflict the elderly,
      particularly Alzheimer's disease. The reasons for this selective vulnerability
      remain poorly understood. Given that intraneuronal accumulation of the amyloid
      beta peptide (Abeta) has been shown to exert deleterious effects on neurons, we
      tested potential accumulation of Abeta within BFCN in rhesus monkeys, which like
      the human display age-related accumulation of this peptide in plaques. The non
      isoform-specific Abeta antibodies 1282 and 6E10 and the specific antibodies to 1
      40 amino acid isoform of Abeta (Abeta1-40) and 1-42 amino acid isoform of Abeta
      (Abeta1-42) species were used in immunohistochemical experiments of basal
      forebrain in young and aged rhesus monkeys. All four antibodies visualized
      cortical plaques in the same sections in which BFCN were examined, in aged but
      not in young animals. The basal forebrain region within which the BFCN are
      localized was virtually free of plaques. Appreciable Abeta immunoreactivity was
      present within the nucleus basalis of Meynert-cholinergic cell group 4 (nbM-Ch4),
      the major component of BFCN, with all antibodies used. Quantitation of optical
      density indicated significant age-related increases in immunoreactivity in nbM
      Ch4 neurons with the Abeta1-40 (p<0.002) and 1282 (p<0.03) antibodies.
      Immunoreactivity for 6E10 displayed a small, non-significant age-related increase
      in nbM-Ch4 neurons (p>0.05). No age-related changes were detected in Abeta1-42
      immunoreactivity in these neurons. Unlike the BFCN, cortical neurons within the
      same sections were virtually devoid of Abeta immunoreactivity, particularly with
      isoform-specific antibodies. Both smooth and granular intraneuronal Abeta
      immunoreactivity, reminiscent of endosomal/lysosomal packaged peptide, were
      observed within nbM-Ch4 neurons. In some nbM-Ch4 neurons, 1282 immunoreactivity
      had the appearance of large peptide aggregates. Significant accumulation and age
      related increase of Abeta in BFCN is likely to interfere with the normal
      functioning of these neurons. It remains to be determined if similar accumulation
      of Abeta occurs in human BFCN. 

PMID- 25869620
TI  - Evidence for beta corticomuscular coherence during human standing balance:
      Effects of stance width, vision, and support surface.
AB  - The role of the cerebral cortex in maintaining human standing balance remains
      unclear. Beta corticomuscular coherence (CMC) provides a measure of communication
      between the sensory-motor cortex and muscle, but past literature has not
      demonstrated significant beta CMC during human stance. This study evaluated the
      effects of stance width, vision, and surface compliance on beta CMC during human
      stance using methods to enhance sensitivity to CMC. Ten healthy, young adults
      stood for three 60-s trials in each of a wide or narrow stance width while on a
      firm surface and in narrow stance on a foam surface, each with eyes open or
      closed. Beta CMC was calculated between contralateral electroencephalographic and
      electromyographic recordings. Electromyography was recorded from bilateral
      tibialis anterior and gastrocnemius lateralis muscles. CMC magnitude was defined
      as the average integrated area of coherence spectrum above a significance
      threshold. Measures of center-of-pressure (COP) sway were derived from force
      plates under the subjects' feet. Results of CMC from four muscles across six
      stance conditions (a total of 24 combinations) demonstrated significant average
      CMC magnitude from every subject in 20 combinations and significant average CMC
      magnitude in nine of 10 subjects in the remaining four combinations. The CMC
      magnitude was significantly larger in the wide-stance condition than in the
      narrow-stance condition with eyes open. No significant differences were detected
      when comparing eyes-open to eyes-closed conditions or when comparing firm- to
      foam-surface conditions. Correlations between CMC magnitude and COP sway elicited
      some significant relationships, but there was no consistent direction or pattern
      of correlation based on muscle or stance condition. Results demonstrate that
      significant beta CMC is evident during human standing balance, and that beta CMC
      is responsive to changes in mechanical, but not visual or surface, conditions. 

PMID- 25869621
TI  - Presynaptic inhibition of soleus Ia afferents does not vary with center of
      pressure displacements during upright standing.
AB  - The present work was designed to investigate the presynaptic modulation of soleus
      Ia afferents with the position and the direction of the displacement of the
      center of pressure (CoP) during unperturbed upright standing and exaggerated CoP
      displacements in young adults. Hoffmann (H) reflex was evoked in the soleus by
      stimulating the tibial nerve at the knee level. Modulation of Ia presynaptic
      inhibition was assessed by conditioning the H reflex with fibular nerve (D1
      inhibition) and femoral nerve (heteronymous facilitation) stimulation. Leg muscle
      activity was assessed by electromyography (EMG). The results indicate that in
      unperturbed standing and exaggerated CoP displacements, the H-reflex amplitude
      was greater during forward than backward CoP direction (p<0.05). However, the
      amplitude of the conditioned H reflex (expressed relative to unconditioned H
      reflex) did not vary with CoP displacement, regardless of the experimental
      condition. The soleus EMG was greater during forward than backward CoP direction
      and during anterior than posterior position in both experimental conditions
      (p<0.05). The modulation of the unconditioned H reflex with CoP direction was
      positively associated with the corresponding changes in soleus EMG (r(2)>0.34).
      The tibialis anterior EMG did not change during unperturbed standing, but was
      greater for backward than forward CoP direction during exaggerated CoP
      displacements. In this experimental condition, soleus EMG was negatively
      associated with tibialis anterior EMG (r(2)=0.81). These results indicate that Ia
      presynaptic inhibition is not modulated with CoP direction and position, but
      rather suggest that CoP displacements induced changes in excitability of the
      soleus motor neuron pool. 

PMID- 25869622
TI  - Hippocampal sharp waves and ripples: Effects of aging and modulation by NMDA
      receptors and L-type Ca2+ channels.
AB  - Aging is accompanied by a complicated pattern of changes in the brain
      organization and often by alterations in specific memory functions. One of the
      brain activities with important role in the process of memory consolidation is
      thought to be the hippocampus activity of sharp waves and ripple oscillation
      (SWRs). Using field recordings from the CA1 area of hippocampal slices we
      compared SWRs as well as single pyramidal cell activity between adult (3-6-month
      old) and old (24-34-month old) Wistar rats. The slices from old rats displayed
      ripple oscillation with a significantly less number of ripples and lower
      frequency compared with those from adult animals. However, the hippocampus from
      old rats had significantly higher propensity to organized SWRs in long sequences.
      Furthermore, the bursts recorded from complex spike cells in slices from old
      compared with adult rats displayed higher number of spikes and longer mean inter
      spike interval. Blockade of N-methyl-D-aspartic acid (NMDA) receptors by 3-((R)-2
      carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) increased the amplitude of
      both sharp waves and ripples and increased the interval between events of SWRs in
      both age groups. On the contrary, CPP reduced the probability of occurrence of
      sequences of SWRs more strongly in slices from adult than old rats. Blockade of L
      type voltage-dependent calcium channels by nifedipine only enhanced the amplitude
      of sharp waves in slices from adult rats. CPP increased the postsynaptic
      excitability and the paired-pulse inhibition in slices from both adult and old
      rats similarly while nifedipine increased the postsynaptic excitability only in
      slices from adult rats. We propose that the tendency of the aged hippocampus to
      generate long sequences of SWR events might represent the consequence of
      homeostatic mechanisms that adaptively try to compensate the impairment in the
      ripple oscillation in order to maintain the behavioral outcome efficient in the
      old individuals. The age-dependent alterations in the firing mode of pyramidal
      cells might underlie to some extent the changes in ripples that occur in old
      animals.

PMID- 25869623
TI  - ERK1/2 is a key regulator of Fndc5 and PGC1alpha expression during neural
      differentiation of mESCs.
AB  - Fibronectin type III domain containing 5 (Fndc5) has already been distinguished
      to be involved in neural differentiation. However, cellular events of Fndc5
      function are still ambiguous in the nervous system. One approach to shed light on
      duty of this protein in the nervous system is to find its cross-talks with
      various signaling pathways with defined characteristics and roles. Identification
      of the underlying molecular mechanism which controls Fndc5 expression and
      switches its activity up and down enables us to find out the Fndc5 functional map
      in the nervous system and other human body systems. Retinoic acid (RA) is a bio
      small molecule which exerts its role as a neural inducer in the
      neurodevelopmental process of neural tube. RA up-regulates the expression of
      various genes involved in neural differentiation process via two distinct
      pathways: the genomic and the non-genomic. Our previous study has revealed that
      RA induces Fndc5 expression during neural differentiation process. In this study
      we have evaluated our hypothesis about the non-genomic up regulation of Fndc5
      expression by RA. Interestingly we have identified that there is an association
      between ERK signaling pathway and Fndc5 expression. Furthermore, inhibition of
      this pathway by PD0325901 dramatically reduced Fndc5 mRNA level, while activating
      the pathway up-regulated Fndc5 transcription. In addition, it has been proven
      that ERK1/2 modulation via RA has more significant controlling effect on Fndc5
      promoter rather than bFGF. This led us to conclude that RA enhances Fndc5
      expression through a non-genomic pathway via the ERK signaling pathway. 

PMID- 25869624
TI  - Alteration of major vault protein in human glioblastoma and its relation with
      EGFR and PTEN status.
AB  - Glioblastoma (GBM) is the most frequent and malignant primary brain tumor.
      Conventional therapy of surgical removal, radiation and chemotherapy is largely
      palliative. Major vault protein (MVP), the main component of the vault organelle
      has been associated with multidrug resistance by reducing cellular accumulation
      of chemotherapeutic agents. With regard to cancer, MVP has been shown to be
      overexpressed in drug resistance development and malignant progression. The aim
      of the present study was to evaluate the MVP gene dosage levels in 113 archival
      samples from GBM and its correlation with patients' survival and epidermal growth
      factor receptor (EGFR) and phosphatase and tensin homolog (PTEN) gene dosages.
      Fluorescent in situ hybridization revealed polysomy of chromosome 7 in 76.1% of
      the GBMs and EGFR amplification in a 64.6% of the tumors. Genetic status of EGFR,
      PTEN and MVP copies was determined by multiplex ligation-dependent probe
      amplification (MLPA) technique. 31% of the tumors showed the EGFR is variant III
      mutation (EGFRvIII) mutation and 74.3% of them presented amplification of MVP
      gene. Amplification of EGFR and MVP was found in a 63.7% and 56.6% of the GBM,
      respectively. An inverse correlation between MVP and PTEN dosage values was
      observed. Besides, an inverse relationship between the survival of the patients
      treated with chemotherapy and the levels of MVP copies was determined. In
      conclusion, our study reveals an important role of MVP, together with EGFRvIII
      and PTEN, in the progression of GBM and proposes it as a novel and interesting
      target for new treatment approaches. 

PMID- 25869625
TI  - Evaluation of a Remote Monitoring System for Diabetes Control.
AB  - PURPOSE: The use of technology to implement cost-effective health care management
      on a large scale may be an alternative for diabetes management but needs to be
      evaluated in controlled trials. This study assessed the utility and cost
      effectiveness of an automated Diabetes Remote Monitoring and Management System
      (DRMS) in glycemic control versus usual care. METHODS: In this randomized,
      controlled study, patients with uncontrolled diabetes on insulin were randomized
      to use of the DRMS or usual care. Participants in both groups were followed up
      for 6 months and had 3 clinic visits at 0, 3, and 6 months. The DRMS used text
      messages or phone calls to remind patients to test their blood glucose and to
      report results via an automated system, with no human interaction unless a
      patient had severely high or low blood glucose. The DRMS made adjustments to
      insulin dose(s) based on validated algorithms. Participants reported medication
      adherence through the Morisky Medication Adherence Scale-8, and diabetes-specific
      quality of life through the diabetes Daily Quality of Life questionnaire. A cost
      effectiveness analysis was conducted based on the estimated overall costs of DRMS
      and usual care. FINDINGS: A total of 98 patients were enrolled (59 [60%] female;
      mean age, 59 years); 87 participants (89%) completed follow-up. HbA1c was similar
      between the DRMS and control groups at 3 months (7.60% vs 8.10%) and at 6 months
      (8.10% vs 7.90%). Changes from baseline to 6 months were not statistically
      significant for self-reported medication adherence and diabetes-specific quality
      of life, with the exception of the Daily Quality of Life-Social/Vocational
      Concerns subscale score (P = 0.04). IMPLICATIONS: An automated system like the
      DRMS may improve glycemic control to the same degree as usual clinic care and may
      significantly improve the social/vocational aspects of quality of life. Cost
      effectiveness analysis found DRMS to be cost-effective when compared to usual
      care and suggests DRMS has a good scale of economy for program scale up. Further
      research is needed to determine how to sustain the benefits seen with the
      automated system over longer periods.

PMID- 25869626
TI  - Statin Prescribing Patterns: An Analysis of Data From Patients With Diabetes in
      the National Hospital Ambulatory Medical Care Survey Outpatient Department and
      National Ambulatory Medical Care Survey Databases, 2005-2010.
AB  - PURPOSE: In 2008, the American Diabetes Association (ADA) recommended that
      patients aged >40 years with diabetes and cardiovascular disease or with >=1
      cardiovascular disease risk factor be prescribed a statin. This study assessed
      statin prescribing patterns in patients with diabetes, per the ADA guideline,
      using data from the National Ambulatory Medical Care Survey and National Hospital
      Ambulatory Medical Care Survey-Outpatient Department for the years 2005 to 2010.
      This study also examined patients' demographic characteristics associated with
      statin prescribing, including sex, age, ethnicity, race, insurance type, body
      mass index, region, primary care provider, hypertension and hyperlipidemia.
      METHODS: This retrospective, cross-sectional, observational study included data
      dated between 2005 and 2010 from patients aged >=18 years with diabetes and
      without contraindications to statin use. Associations between statin prescribing
      and variables of interest were analyzed using chi(2) tests. A multivariate
      logistic regression model included 2 groups stratified by 3-year observation
      period (2005-2007 and 2008-2010) plus all variables with an overall chi(2) test
      result of P < 0.2. P values, odds ratios (ORs) and 95% CIs are reported.
      FINDINGS: The majority of patients were aged >=40 years (93.1%), had a body mass
      index of >=30 (58.7%), had hypertension (65.6%), and did not have hyperlipidemia
      (54.0%). A low percentage of patients were prescribed a statin (35.1%), but it
      appears that this percentage is on the rise. During 2005-2007, 31.9% of patients
      received a statin, whereas 37.7% of patients received a statin during 2008-2010.
      After adjustment for covariates included in the multivariate logistic regression
      model, those with hypertension (vs none [reference]: OR = 1.31; 95% CI, 1.12
      1.53) and/or hyperlipidemia (vs none [reference]: OR = 4.44; 95% CI, 3.70-5.33)
      were significantly more likely to have been prescribed a statin, whereas those in
      age group 18-<40 years (vs 40-<65 years [reference]: OR = 0.45; 95% CI, 0.31
      0.65) and Hispanic/Latino patients (vs non-Hispanic/Latino patients [reference]:
      OR = 0.77; 95% CI, 0.61-0.97) were significantly less likely to have been
      prescribed a statin. IMPLICATIONS: Despite the call in the latest ADA
      recommendations for prescribing statins in many diabetic patients, an
      unexpectedly low percentage of patients were receiving them. Health disparities
      in age and ethnicity were also evident. The findings from this study highlight
      the need for further research into low statin prescribing rates.

PMID- 25869627
TI  - Pharmacokinetic Properties and Tolerability of Cycloserine Following Oral
      Administration in Healthy Chinese Volunteers: A Randomized, Open-Label, Single-
      and Multiple-Dose 3-Way Crossover Study.
AB  - PURPOSE: A new generic formulation of cycloserine has been developed in China but
      the pharmacokinetic properties of cycloserine in the Chinese population have not
      been reported. The aim of our study was to evaluate the pharmacokinetic
      properties and tolerability of single and multiple oral administrations of
      cycloserine capsules in healthy Chinese volunteers. METHODS: This open-label,
      single- and multiple-dose 3-way crossover study was conducted in healthy Chinese
      volunteers. Subjects were randomized to receive a single dose of cycloserine
      (250, 500, or 1000 mg) in separate trial periods, with a 1-week washout between
      periods. Those allocated to the 250-mg dose continued into the multiple-dose
      phase, in which they received 250 mg BID for 5 consecutive days. During the
      single-dose phase, blood samples were collected at regular intervals from 0 to 72
      hours after drug administration and the concentrations of cycloserine were
      determined using LC-MS/MS. During the multiple-dose phase, blood samples were
      obtained before drug administration on Days 4, 5, and 6 to determine the Cmin at
      steady state. On Day 6, blood samples were also collected from 0 to 72 hours
      after drug administration. Pharmacokinetic parameters were estimated using
      noncompartmental methods. Tolerability was determined using clinical evaluation
      and monitoring of adverse events. FINDINGS: The study enrolled 12 healthy Chinese
      volunteers (6 men: mean [SD] age = 23.0 [2.6] years, weight = 60.2 [6.2] kg,
      height = 170.0 [3.0] cm, and body mass index = 20.7 [1.7]; 6 women: mean [SD] age
      = 25.3 [1.4] years, weight = 51.5 [3.3] kg, height = 160.0 [4.0] cm, and body
      mass index = 20.1 [0.9]). After administration of a single dose, cycloserine was
      rapidly absorbed, reaching peak plasma concentrations approximately 0.84 hours
      after oral administration, and t1/2 in plasma was about 13.0 hours. The geometric
      mean (SD) Cmax value increased in proportion to cycloserine dose, from 19.42
      (5.89) to 84.76 (21.74) mg/L, and the geometric mean (SD) AUC0-72h value
      increased from 264.16 (133.37) to 1153.87 (522.16) mg.h/L in the range of a 250-
      to 1000-mg dose. After administration of multiple doses of cycloserine 250 mg
      BID, the mean (SD) t1/2 was 13.56 (4.38) hours, the apparent total clearance of
      the drug from plasma after oral administration was 1.02 (0.42) L/h, and the
      apparent volume of distribution was 18.22 (5.25) L, which were comparable with
      those after single dosing. The accumulation index was 2.19 (0.51), and the
      fluctuation was 1.05 (0.35). Results of the t tests of Cmax and AUC found no
      significant differences between the male and female groups. No serious adverse
      events were reported, and there were no discontinuations due to adverse events.
      IMPLICATIONS: The pharmacokinetic properties of cycloserine were linear at doses
      from 250 mg to 1000 mg. After multiple doses, the pharmacokinetic properties of
      cycloserine were consistent with those after single doses. At the doses studied,
      cycloserine appears to be well tolerated in these healthy volunteers. Chinese
      Clinical Trials registration: ChiCTR-TTRCC-13003982.

PMID- 25869628
TI  - A Retrospective, Pooled Suicidality Evaluation of Ropinirole Immediate Release
      and Controlled Release for the Treatment of Restless Legs Syndrome.
AB  - PURPOSE: Based on an internal request, GlaxoSmithKline conducted a retrospective
      pooled analysis of randomized controlled trials to compare suicidality in adult
      subjects with restless legs syndrome (RLS) who were being treated with
      ropinirole. The objective was to proactively evaluate the incidence of
      potentially suicidal thoughts or behaviors (suicidality) among patients with RLS
      treated with ropinirole immediate release (IR) or controlled release (CR).
      METHODS: The US Food and Drug Administration approved methods previously used for
      the retrospective analysis of suicidality with antidepressants and
      anticonvulsants. Potential cases of suicidal thoughts and behavior were
      identified from searches of treatment-emergent adverse event preferred and
      verbatim terms; a review of serious adverse events; and searches of a priori
      identified free text comment fields in the case report forms. Blinded case
      reports for these potential cases, in addition to all serious adverse events,
      were categorized by using the Columbia Classification Algorithm of Suicide
      Assessment. FINDINGS: The dataset for this study comprised 1799 patients who
      received ropinirole (either formulation) and 1258 patients who received placebo.
      No signal for suicidality was detected for ropinirole in the treatment of
      patients with RLS. IMPLICATIONS: The pooled datasets in this study were not
      designed to prospectively assess for suicidal ideation or behavior. Any future
      studies in this area should include the collection of prespecified, detailed
      information regarding suicidality.

PMID- 25869629
TI  - Provider barriers to family planning access in urban Kenya.
AB  - OBJECTIVE: A better understanding of the prevalence of service provider-imposed
      barriers to family planning can inform programs intended to increase
      contraceptive use. This study, based on data from urban Kenya, describes the
      frequency of provider self-reported restrictions related to clients' age, parity,
      marital status, and third-party consent, and considers the impact of facility
      type and training on restrictive practices. STUDY DESIGN: Trained data collectors
      interviewed 676 service providers at 273 health care facilities in five Kenyan
      cities. Service providers were asked questions about their background and
      training and were also asked about age, marital, parity, or consent requirements
      for providing family planning services. RESULTS: More than half of providers
      (58%) reported imposing minimum age restrictions on one or more methods. These
      restrictions were commonly imposed on clients seeking injectables, a popular
      method in urban Kenya, with large numbers refusing to offer injectables to women
      younger than 20 years. Forty-one percent of providers reported that they would
      not offer one or more methods to nulliparous women and more than one in four
      providers reported that they would not offer the injectable to women without at
      least one child. Providers at private facilities were significantly more likely
      to impose barriers, across all method types, and those without in-service
      training on family planning provision had a significantly higher prevalence of
      imposing parity, marital, and consent barriers across most methods. CONCLUSION:
      Programs need to address provider-imposed barriers that reduce access to
      contraceptive methods particularly among young, lower parity, and single women.
      Promising strategies include targeting private facility providers and increasing
      the prevalence of in-service training.

PMID- 25869630
TI  - Do as we say, not as we do: experiences of unprotected intercourse reported by
      members of the Society of Family Planning.
AB  - OBJECTIVES: We examine the lifetime and past-year prevalence and circumstances of
      unprotected intercourse among members of the Society of Family Planning (SFP), a
      professional reproductive health organization in the United States. STUDY DESIGN:
      We invited the membership of SFP (n=477) via email to participate in an anonymous
      online survey. The response rate was 70% (n=340). We asked whether respondents
      had ever and in the past year had unprotected vaginal intercourse when not
      intending a pregnancy and, if so, how many times, under what circumstances, and
      at what age the first time. We then asked about unprotected vaginal, anal, or
      oral intercourse ever and in the past year under three different scenarios
      relating to sexually transmitted infections (STIs): (1) partner STI status
      unknown, respondent STI-free; (2) partner known infected, respondent STI-free;
      (3) partner STI-free, respondent STI status unknown or known infected. Each
      scenario included questions about the number of times, applicable circumstances,
      and age at first time. RESULTS: Forty-six percent of respondents had ever had
      unprotected vaginal intercourse when not intending pregnancy, 7% within the past
      year. Sixty percent had ever had unprotected vaginal, anal, or oral intercourse
      with a partner whose STI status was unknown, 12% within the past year. Four
      percent had ever had unprotected intercourse with a partner known to have STI,
      and 8%, with an STI-free partner when they themselves either had an STI or did
      not know their STI status. CONCLUSIONS: Ever having taken a risk with respect to
      pregnancy and/or STIs is common among our sample of reproductive health
      professionals. IMPLICATIONS: Most reproductive healthcare professionals in our
      sample have taken sexual risks in their lifetime and a small proportion has done
      so in the past year. These findings could inform counseling by encouraging
      healthcare professionals to reflect upon their own experiences when developing
      strategies to promote safe sex among their patients.

PMID- 25869631
TI  - Safety of the progesterone-releasing vaginal ring (PVR) among lactating women: A
      systematic review.
AB  - CONTEXT: Lactation causes a delay in ovulation in the postpartum period, and
      therefore a delay in the resumption of menses. However, return to fertility is
      variable in the postpartum period and is contingent upon numerous factors. The
      postpartum period is therefore a critical time to initiate effective
      contraception in order to support the numerous beneficial health outcomes of
      optimal pregnancy spacing. Breastfeeding women have an unmet need for highly
      effective birth control methods that do not interfere with lactation and that are
      safe for their infants. The progesterone-releasing vaginal ring (PVR) releases a
      natural progesterone that suppresses ovulation and is specifically designed for
      breastfeeding women in the first postpartum year. OBJECTIVE: To review the
      published peer-reviewed literature regarding the safety and effectiveness of the
      PVR used for contraception among lactating women, as well as the safety for their
      infants. Results of this review informed the decisions of the Guideline
      Development Group to include recommendations on contraceptive eligibility for the
      PVR within the World Health Organization Medical Eligibility Criteria for
      Contraceptive Use, 5th Edition. METHODS: We searched the PubMed, Popline, and
      LILACS bibliographic databases for articles published in any language from
      database inception through October 1, 2014. We reviewed the literature for
      evidence regarding the safety of the PVR among breastfeeding women using the
      method, as well as for their infants. The US Preventive Services Task Force
      system was applied to assess the quality of the evidence. RESULTS: Seven articles
      met our criteria for inclusion in this review. All studies were of a prospective
      cohort design. All studies consistently showed that use of the PVR among
      breastfeeding women compares favorably to other methods of contraception with
      regard to effectiveness, does not compromise a woman's breastfeeding performance,
      and does not adversely affect infant growth during the first year postpartum.
      CONCLUSION: The PVR is a safe and highly effective method of contraception for
      use among breastfeeding women. It should be offered to women who plan to
      breastfeed in the context of postpartum contraceptive counseling.

PMID- 25869632
TI  - Abortion access and state variation in observed unintended pregnancy.
AB  - OBJECTIVE: The state-level proportion of pregnancies that are unintended is an
      important social and public health indicator, and comparisons between states
      inform policy discussions. Unintended pregnancy is measured as a composite of
      abortions and unintended births, each of which is measured with error. We
      investigate whether between-state differences in abortion access and demand may
      bias comparisons between states' unintended pregnancy proportions when pregnancy
      intentions are misreported. STUDY DESIGN: We algebraically specify the model
      currently used to estimate unintended pregnancy, extend it to include
      underreporting, and simulate the impact of underreporting on observed unintended
      pregnancy. Comparing the impact of underreporting across states, we identify
      levels of underreporting at which between-state comparisons are compromised.
      RESULTS: We find that underreporting of unintended pregnancies could bias between
      state comparisons when reporting of unintended pregnancies is less than 90-95%.
      CONCLUSION: Current methods for estimating state-level unintended pregnancy
      proportions may underestimate unintended pregnancy to a greater degree in places
      with less abortion, and between-state comparisons may be biased. Estimates of
      state-level unintended pregnancy proportions would be more comparable if
      adjustment for completeness of retrospective underreporting were included in the
      estimation process. IMPLICATIONS: Estimates of unintended pregnancy should be
      adjusted for nonsampling error and include variances based on sampling and
      nonsampling error in order to permit robust comparisons between states, between
      populations, and across time. More research on the fidelity of retrospective
      reporting of pregnancy intention would facilitate this endeavor.

PMID- 25869633
TI  - Effects of different elevated CO2 concentrations on chlorophyll contents, gas
      exchange, water use efficiency, and PSII activity on C3 and C4 cereal crops in a
      closed artificial ecosystem.
AB  - Although terrestrial CO2 concentrations [CO2] are not expected to reach 1000
      MUmol mol(-1) (or ppm) for many decades, CO2 levels in closed systems such as
      growth chambers and greenhouses can easily exceed this concentration. CO2 levels
      in life support systems (LSS) in space can exceed 10,000 ppm (1 %). In order to
      understand how photosynthesis in C4 plants may respond to elevated CO2, it is
      necessary to determine if leaves of closed artificial ecosystem grown plants have
      a fully developed C4 photosynthetic apparatus, and whether or not photosynthesis
      in these leaves is more responsive to elevated [CO2] than leaves of C3 plants. To
      address this issue, we evaluated the response of gas exchange, water use
      efficiency, and photosynthetic efficiency of PSII by soybean (Glycine max (L.)
      Merr., 'Heihe35') of a typical C3 plant and maize (Zea mays L., 'Susheng') of C4
      plant under four CO2 concentrations (500, 1000, 3000, and 5000 ppm), which were
      grown under controlled environmental conditions of Lunar Palace 1. The results
      showed that photosynthetic pigment by the C3 plants of soybean was more sensitive
      to elevated [CO2] below 3000 ppm than the C4 plants of maize. Elevated [CO2] to
      1000 ppm induced a higher initial photosynthetic rate, while super-elevated [CO2]
      appeared to negate such initial growth promotion for C3 plants. The C4 plant had
      the highest ETR, phiPSII, and qP under 500-3000 ppm [CO2], but then decreased
      substantially at 5000 ppm [CO2] for both species. Therefore, photosynthetic down
      regulation and a decrease in photosynthetic electron transport occurred by both
      species in response to super-elevated [CO2] at 3000 and 5000 ppm. Accordingly,
      plants can be selected for and adapt to the efficient use of elevated CO2
      concentration in LSS. 

PMID- 25869634
TI  - Effects of ocean acidification on the photosynthetic performance, carbonic
      anhydrase activity and growth of the giant kelp Macrocystis pyrifera.
AB  - Under ocean acidification (OA), the 200 % increase in CO2(aq) and the reduction
      of pH by 0.3-0.4 units are predicted to affect the carbon physiology and growth
      of macroalgae. Here we examined how the physiology of the giant kelp Macrocystis
      pyrifera is affected by elevated pCO2/low pH. Growth and photosynthetic rates,
      external and internal carbonic anhydrase (CA) activity, HCO3 (-) versus CO2 use
      were determined over a 7-day incubation at ambient pCO2 400 uatm/pH 8.00 and a
      future OA treatment of pCO2 1200 uatm/pH 7.59. Neither the photosynthetic nor
      growth rates were changed by elevated CO2 supply in the OA treatment. These
      results were explained by the greater use of HCO3 (-) compared to CO2 as an
      inorganic carbon (Ci) source to support photosynthesis. Macrocystis is a mixed
      HCO3 (-) and CO2 user that exhibits two effective mechanisms for HCO3 (-)
      utilization; as predicted for species that possess carbon-concentrating
      mechanisms (CCMs), photosynthesis was not substantially affected by elevated
      pCO2. The internal CA activity was also unaffected by OA, and it remained high
      and active throughout the experiment; this suggests that HCO3 (-) uptake via an
      anion exchange protein was not affected by OA. Our results suggest that
      photosynthetic Ci uptake and growth of Macrocystis will not be affected by
      elevated pCO2/low pH predicted for the future, but the combined effects with
      other environmental factors like temperature and nutrient availability could
      change the physiological response of Macrocystis to OA. Therefore, further
      studies will be important to elucidate how this species might respond to the
      global environmental change predicted for the ocean.

PMID- 25869635
TI  - Analysis of spontaneous suppressor mutants from the photomixotrophically grown
      pmgA-disrupted mutant in the cyanobacterium Synechocystis sp. PCC 6803.
AB  - The pmgA-disrupted (DeltapmgA) mutant in the cyanobacterium Synechocystis sp. PCC
      6803 suffers severe growth inhibition under photomixotrophic conditions. In order
      to elucidate the key factors enabling the cells to grow under photomixotrophic
      conditions, we isolated spontaneous suppressor mutants from the DeltapmgA mutant
      derived from a single colony. When the DeltapmgA mutant was spread on a BG11 agar
      plate supplemented with glucose, colonies of suppressor mutants appeared after
      the bleaching of the background cells. We identified the mutation site of these
      suppressor mutants and found that 11 mutants out of 13 had a mutation in genes
      related to the type 1 NAD(P)H dehydrogenase (NDH-1) complex. Among them, eight
      mutants had mutations within the ndhF3 (sll1732) gene: R32stop, W62stop, V147I,
      G266V, G354W, G586C, and deletion of 7 bp within the coding region. One mutant
      had one base insertion in the putative -10 box of the ndhC (slr1279) gene,
      leading to the decrease in the transcripts of the ndhCKJ operon. Two mutants had
      one base insertion and deletion in the coding region of cupA (sll1734), which is
      co-transcribed with ndhF3 and ndhD3 and comprises together a form of NDH-1
      complex (NDH-1MS complex) involved in inducible high-affinity CO2 uptake. The
      results indicate that the loss of the activity of this complex effectively
      rescues the DeltapmgA mutant under photomixotrophic condition with 1 % CO2.
      However, little difference among WT and mutants was observed in the activities
      ascribed to the NDH-1MS complex, i.e., CO2 uptake and cyclic electron transport.
      This may suggest that the NDH-1MS complex has the third, currently unknown
      function under photomixotrophic conditions. 

PMID- 25869636
TI  - Acute Anxiety and Anxiety Disorders Are Associated With Impaired Gastric
      Accommodation in Patients With Functional Dyspepsia.
AB  - BACKGROUND & AIMS: Functional dyspepsia (FD) is associated with impaired gastric
      accommodation, as well as gastric hypersensitivity, delayed emptying, and
      psychosocial comorbidities. In healthy people, acute anxiety impairs gastric
      accommodation, which is traditionally quantified as the average increase in
      gastric volume after a meal over 1 hour. However, this quantification approach
      does not address the complex time course of the gastric accommodation response to
      a meal. We modeled gastric accommodation in patients with FD as a function of
      postprandial time, to investigate whether it is associated with psychosocial
      factors (state anxiety, anxiety disorder, depression) and gastric sensorimotor
      function (sensitivity, emptying). METHODS: We studied gastric sensorimotor
      function in 259 consecutive patients diagnosed with FD based on Rome II at the
      University Hospitals Leuven from January 2002 through February 2009. Subjects
      underwent a gastric barostat and breath test; psychiatric comorbidity was
      assessed by questionnaires. Subjects completed the State-Trait Anxiety Inventory
      to measure levels of state anxiety immediately before and after gastric barostat
      analysis. The time course of the accommodation response was analyzed using mixed
      models. Psychological and sensorimotor variables were added to the model as
      continuous (state anxiety) or dichotomous (gastric sensitivity and emptying,
      anxiety disorders, depression) covariates, including their interaction with the
      time effects. RESULTS: In subjects with FD, delayed emptying (beta = 50.3 +/-
      15.9; P = .002) and lower state anxiety (beta = -1.7 +/- 0.7; P = .012) were
      associated with an upward shift of the accommodation curve. There was a
      significant interaction between comorbid anxiety disorder and linear (beta = 8.2
      +/- 3.5; P = .02), quadratic (beta = -0.4 +/- 0.1; P = .004), and cubic (beta =
      0.005 +/- 0.002; P = .002) effects of time: patients with a comorbid anxiety
      disorder had significantly slower initial increases in gastric volume to a lower
      maximum, and a slower return to baseline, compared with patients without anxiety
      disorder. Depression and gastric sensitivity were not associated significantly
      with gastric accommodation. CONCLUSIONS: In patients with FD, state anxiety and
      comorbid anxiety disorders are associated with impaired accommodation; gastric
      emptying also is associated with accommodation in these patients. These findings
      help elucidate the complex interactions between psychological processes and
      disorders, gastric sensorimotor dysfunction, and symptom reporting in patients
      with FD.

PMID- 25869637
TI  - Spicing up the Treatment of Mild to Moderate Ulcerative Colitis.

PMID- 25869638
TI  - Relationship Among Anal Sphincter Injury, Patulous Anal Canal, and Anal Pressures
      in Patients With Anorectal Disorders.
AB  - BACKGROUND & AIMS: The anal sphincters and puborectalis are imaged routinely with
      an endoanal magnetic resonance imaging (MRI) coil, which does not assess co
      aptation of the anal canal at rest. By using a MRI torso coil, we identified a
      patulous anal canal in some patients with anorectal disorders. We aimed to
      evaluate the relationship between anal sphincter and puborectalis injury, a
      patulous anal canal, and anal pressures. METHODS: We performed a retrospective
      analysis of data from 119 patients who underwent MRI and manometry analysis of
      anal anatomy and pressures, respectively, from February 2011 through March 2013
      at the Mayo Clinic. Anal pressures were determined by high-resolution manometry,
      anal sphincter and puborectalis injury was determined by endoanal MRI, and anal
      canal integrity was determined by torso MRI. Associations between manometric and
      anatomic parameters were evaluated with univariate and multivariate analyses.
      RESULTS: Fecal incontinence (55 patients; 46%) and constipation (36 patients;
      30%) were the main indications for testing; 49 patients (41%) had a patulous anal
      canal, which was associated with injury to more than 1 muscle (all P <= .001),
      and internal sphincter (P < .01), but not puborectalis (P = .09) or external
      sphincter (P = .06), injury. Internal (P < .01) and external sphincter injury (P
      = .02) and a patulous canal (P < .001), but not puborectalis injury, predicted
      anal resting pressure. A patulous anal canal was the only significant predictor
      (P < .01) of the anal squeeze pressure increment. CONCLUSIONS: Patients with
      anorectal disorders commonly have a patulous anal canal, which is associated with
      more severe anal injury and independently predicted anal resting pressure and
      squeeze pressure increment. It therefore is important to identify a patulous anal
      canal because it appears to be a marker of not only anal sphincter injury but
      disturbances beyond sphincter injury, such as damage to the anal cushions or anal
      denervation.

PMID- 25869639
TI  - Long-term impact of childhood-onset type 1 diabetes on social life, quality of
      life and sexuality.
AB  - AIM: This study describes the socio-professional outcomes, health-related quality
      of life (HRQOL) and sexuality of adults with childhood-onset type 1 diabetes
      (T1D). METHODS: The study participants (n=388), recruited from a nationwide
      registry (age: 28.5 +/- 3.1 years; T1D duration: 17.0 +/- 2.7 years), completed a
      questionnaire (198 items); the results were compared with the French general
      population using standardized incidence ratios (SIRs) and Z scores matched for
      age, gender and period with/without education levels and patterns of family life.
      Linear regression models also investigated correlates of SF-36 Physical (PCS) and
      Mental Composite Scores (MCS). RESULTS: Compared with the French general
      population, education levels of people with T1D were similar, with 68.6% having
      at least a high-school diploma or higher (SIR: 1.06, 95% CI: 0.93; 1.20), as were
      also their patterns of family life. Unemployment was higher in T1D women (15.3%,
      SIR: 1.50, 1.00; 2.05), but not in T1D men (8.6%, SIR: 0.96, 0.51; 1.57). Social
      discrimination was more common (SIR: 5.64, 4.64; 6.62), and frequency of daily
      alcohol consumption was higher (SIR: men, 3.34, 2.38; 4.54; women, 6.53, 4.57;
      12.99). PCS and MCS were decreased moderately (mean +/- SD: 52.0 +/- 7.5; mean Z
      score: -0.2, 95% CI: -0.3; -0.1) and substantially (mean +/- SD: 42.1 +/- 12.4;
      mean Z score: -0.7, -0.8; -0.6), respectively. Fatigue and abandoning sports were
      predictive of a lower HRQOL. Both men and women were more frequently dissatisfied
      with their sex life. Prevalence of sexual problems was higher in women (SIR for:
      dysorgasmia, 1.91, 1.21-2.88; decreased/loss of desire: 2.11, 1.35-3.08), but
      similar in men. Participants with T1D-related complications had preserved social
      outcomes, but altered HRQOL. CONCLUSION: Young adults with T1D have satisfactory
      social participation. However, their higher alcohol consumption, lower MCS and
      frequent dissatisfaction with sexuality suggest a heavy impact of the disease on
      morale, especially in women. Improving the everyday well-being of these young
      adults represents a key challenge for diabetes healthcare.

PMID- 25869640
TI  - A role for GPR55 in human placental venous endothelial cells.
AB  - Endocannabinoids and their G protein-coupled receptors have been suggested to
      play a key role in human pregnancy, by regulating important aspects such as
      implantation, decidualization, placentation and labor. G protein-coupled receptor
      55 (GPR55) was previously postulated to be another cannabinoid receptor, since
      specific cannabinoids were shown to act independently of the classical
      cannabinoid receptors CB1 or CB2. Current knowledge about GPR55 expression and
      function in human placenta is very limited and motivated us to evaluate human
      placental GPR55 expression in relation to other human peripheral tissues and to
      analyze spatiotemporal GPR55 expression in human placenta. Gene expression
      analysis revealed low GPR55 levels in human placenta, when compared to spleen and
      lung, the organs showing highest GPR55 expression. Moreover, expression analysis
      showed 5.8 fold increased placental GPR55 expression at term compared to first
      trimester. Immunohistochemistry located GPR55 solely at the fetal endothelium of
      first trimester and term placentas. qPCR and immunocytochemistry consistently
      confirmed GPR55 expression in isolated primary placental arterial and venous
      endothelial cells. Incubation with L-alpha-lysophosphatidylinositol (LPI), the
      specific and functional ligand for GPR55, at a concentration of 1 uM,
      significantly enhanced migration of venous, but not arterial endothelial cells.
      LPI-enhanced migration was inhibited by the GPR55 antagonist O-1918, suggesting a
      role of the LPI-GPR55 axis in placental venous endothelium function.

PMID- 25869643
TI  - Benzofurocarbazole and benzothienocarbazole as donors for improved quantum
      efficiency in blue thermally activated delayed fluorescent devices.
AB  - Benzofurocarbazole and benzothienocarbazole were used as electron donors of
      thermally activated delayed fluorescence (TADF) emitters and the performances of
      the TADF devices were examined. The benzofurocarbazole and benzothienocarbazole
      donor moieties were better than carbazole as the electron donors of the TADF
      emitters. 

PMID- 25869641
TI  - Extracellular association of APP and tau fibrils induces intracellular aggregate
      formation of tau.
AB  - Alzheimer's disease (AD) is characterized by extracellular amyloid beta (Abeta)
      deposition and intracellular tau aggregation. Many studies have indicated some
      association between these processes, but it remains unknown how the two
      pathologies are linked. In this study, we investigated whether expression of
      amyloid precursor protein (APP) influences extracellular seed-dependent
      intracellular tau accumulation in cultured cells. Treatment of tau-expressing SH
      SY5Y cells with Abeta fibrils did not induce intracellular tau aggregation. On
      the other hand, in cells expressing both tau and APP, treatment with tau fibrils
      or Sarkosyl-insoluble tau from AD brains induced intracellular tau aggregation.
      The seed-dependent intracellular tau aggregation was not induced by expression of
      APP lacking the extracellular domain. The amount of phosphorylated tau aggregates
      in cultured cells was dose dependently elevated in response to increased levels
      of APP on the cell membrane. Our results indicate that the extracellular region
      of APP is involved in uptake of tau fibrils into cells, raising the possibility
      that APP, but not Abeta, influences cell-to-cell spreading of tau pathologies in
      AD by serving as a receptor of abnormal tau aggregates. 

PMID- 25869642
TI  - Induction of endogenous Type I interferon within the central nervous system plays
      a protective role in experimental autoimmune encephalomyelitis.
AB  - The Type I interferons (IFN), beta (IFN-beta) and the alpha family (IFN-alpha),
      act through a common receptor and have anti-inflammatory effects. IFN-beta is
      used to treat multiple sclerosis (MS) and is effective against experimental
      autoimmune encephalomyelitis (EAE), an animal model for MS. Mice with EAE show
      elevated levels of Type I IFNs in the central nervous system (CNS), suggesting a
      role for endogenous Type I IFN during inflammation. However, the therapeutic
      benefit of Type I IFN produced in the CNS remains to be established. The aim of
      this study was to examine whether experimentally induced CNS-endogenous Type I
      IFN influences EAE. Using IFN-beta reporter mice, we showed that direct
      administration of polyinosinic-polycytidylic acid (poly I:C), a potent inducer of
      IFN-beta, into the cerebrospinal fluid induced increased leukocyte numbers and
      transient upregulation of IFN-beta in CD45/CD11b-positive cells located in the
      meninges and choroid plexus, as well as enhanced IFN-beta expression by
      parenchymal microglial cells. Intrathecal injection of poly I:C to mice showing
      first symptoms of EAE substantially increased the normal disease-associated
      expression of IFN-alpha, IFN-beta, interferon regulatory factor-7 and IL-10 in
      CNS, and disease worsening was prevented for as long as IFN-alpha/beta was
      expressed. In contrast, there was no therapeutic effect on EAE in poly I:C
      treated IFN receptor-deficient mice. IFN-dependent microglial and astrocyte
      response included production of the chemokine CXCL10. These results show that
      Type I IFN induced within the CNS can play a protective role in EAE and highlight
      the role of endogenous type I IFN in mediating neuroprotection. 

PMID- 25869644
TI  - Molecular markers predicting lymph node metastasis in early esophageal cancer.
AB  - AIMS: The aim of this study was to identify molecular markers predicting depth of
      tumor infiltration and presence of lymph node metastasis in early esophageal
      cancer. METHODS: Between 1996 and 2004, 67 patients with pT1 esophagus cancer
      underwent esophagectomy. Resected tumors and lymph nodes were analyzed by
      immunohistochemistry for tissue infiltration, lymph node metastasis (LNM),
      micrometastasis and extracapsular lymph node infiltration (ELNI). We focused on
      MMP-2 (matrix-metalloproteinase-2), TIMP-2 (tissue inhibitor of metalloproteinase
      2), PIM-1 and survivin as the most promising marker candidates. The data was
      correlated with the patients' long term follow-up (median follow-up time 11.4
      years). RESULTS: We found 22 pT1a and 45 pT1b carcinomas. None of the mucosal
      carcinomas, but 58% (26 patients) of the submucosal carcinomas showed lymph node
      metastasis or micrometastasis. The rate of LNM positively correlated with the
      depth of tumor infiltration (23% LNM in sm1 tumors and 82% LNM in sm3 tumors).
      Low grade PIM-1 expression (<30%) was significantly associated with occurrence of
      LNM (p=0.034) while high expression TIMP-2 (>70%) were detected in submucosal
      tumors. Logistic regression analysis revealed PIM-1 and Grading G3 as independent
      risk factors for LNM (p<0.001). Survival of patients with micrometastasis was
      comparable to those with LNM (median survival: 5.05 years versus 5.52 years).
      Patients with ELNI had the worst prognosis (median survival: 1.7 years).
      CONCLUSIONS: PIM-1 is a promising marker for prediction of lymph node metastasis
      in early esophagus cancer. Extracapsular lymph node infiltration has an
      independent worse prognostic impact.

PMID- 25869645
TI  - Gene expression analysis of two extensively drug-resistant tuberculosis isolates
      show that two-component response systems enhance drug resistance.
AB  - Global analysis of expression profiles using DNA microarrays was performed
      between a reference strain H37Rv and two clinical extensively drug-resistant
      isolates in response to three anti-tuberculosis drug exposures (isoniazid,
      capreomycin, and rifampicin). A deep analysis was then conducted using a
      combination of genome sequences of the resistant isolates, resistance
      information, and related public microarray data. Certain known resistance
      associated gene sets were significantly overrepresented in upregulated genes in
      the resistant isolates relative to that observed in H37Rv, which suggested a link
      between resistance and expression levels of particular genes. In addition,
      isoniazid and capreomycin response genes, but not rifampicin, either obtained
      from published works or our data, were highly consistent with the differentially
      expressed genes of resistant isolates compared to those of H37Rv, indicating a
      strong association between drug resistance of the isolates and genes
      differentially regulated by isoniazid and capreomycin exposures. Based on these
      results, 92 genes of the studied isolates were identified as candidate resistance
      genes, 10 of which are known resistance-related genes. Regulatory network
      analysis of candidate resistance genes using published networks and literature
      mining showed that three two-component regulatory systems and regulator CRP play
      significant roles in the resistance of the isolates by mediating the production
      of essential envelope components. Finally, drug sensitivity testing indicated
      strong correlations between expression levels of these regulatory genes and
      sensitivity to multiple anti-tuberculosis drugs in Mycobacterium tuberculosis.
      These findings may provide novel insights into the mechanism underlying the
      emergence and development of drug resistance in resistant tuberculosis isolates
      and useful clues for further studies on this issue. 

PMID- 25869646
TI  - Polyphenol-rich grape pomace extracts protect against dextran sulfate sodium
      induced colitis in rats.
AB  - BACKGROUND: Several studies have reported that polyphenols may exert beneficial
      effects on inflammatory bowel disease. This study aimed to evaluate the effects
      of preventive consumption of polyphenol-rich red grape pomace extracts (GPEs) on
      dextran sulfate sodium (DSS)-induced colitis in rats. Rats were fed for 21 days
      with a semi-synthetic diet enriched with a GPE (Alicante-S, Alicante-P or Pinot
      S) and colitis was induced by DSS administration in drinking water (40 g L(-1) )
      during the last 7 days of experimentation. RESULTS: GPEs attenuated clinical
      signs and colon shortening and Alicante GPEs limited histological lesions induced
      by DSS. GPEs curbed the increase in myeloperoxidase activity and modulated
      antioxidant enzyme activities. Moreover, GPEs prevented the DSS-induced increase
      in pro-inflammatory cytokine levels and the up-regulation of various genes
      implicated in colitis such as intercellular adhesion molecule 1 (ICAM-1) and
      matrix metalloproteinase 9 (MMP-9). CONCLUSION: These results suggest that
      polyphenol-rich red GPEs could provide prevention against colon inflammation.

PMID- 25869648
TI  - Margaret McCartney: Forever indebted to pharma--doctors must take control of our
      own education.

PMID- 25869649
TI  - Long-term impact of full-thickness rectal prolapse treatment on fecal
      incontinence.
AB  - BACKGROUND: Fecal incontinence is frequently associated with rectal prolapse, but
      little is known about recovery after treatment of the prolapse. OBJECTIVE: We
      therefore aimed to investigate the long-term outcome of fecal incontinence in a
      cohort of patients suffering from full-thickness rectal prolapse. DESIGN: A
      database of 145 patients diagnosed with full-thickness rectal prolapse was
      compiled prospectively over a 7-year period (2003-2010). MAIN OUTCOME MEASURES:
      Patients were referred to a single institution and assessed by standardized
      questionnaires, anorectal manometry, endosonography, and evacuation proctography.
      Fecal incontinence was evaluated according to the Cleveland Clinic Score;
      continence improvement was defined by >=50% improvement of the Cleveland Clinic
      Score. RESULTS: Among the population studied (134 women, 11 men; median follow
      up, 38.9 months [range, 21.2-67.2]), 103 patients (71%) underwent operation for
      their prolapse and 42 (29%) did not. According to the Cleveland Clinic Score, 139
      patients (96%) suffered from fecal incontinence before treatment and 64 (46%)
      reported improvement at the end of the follow-up. Pretreatment history of
      incontinence symptoms for >2 years (hazard ratio [HR], 1.99; 95% CI, 1.14-3.46; P
      = .015) and ventral rectopexy (HR, 1.86; 95% CI, 1.026-3.326; P = .04) were
      associated with continence improvement. Patients who underwent an operative
      procedure other than ventral rectopexy had similar outcome as compared with
      nonoperated patients. Conversely, chronic pelvic pain precluded fecal
      incontinence improvement (HR, 0.32; 95% CI, 0.135-0.668; P = .0017). LIMITATIONS:
      Follow-up, returned questionnaires, and the heterogeneous reasons put forth for
      declining surgery may introduce some methodologic bias. CONCLUSION: Fecal
      incontinence in patients suffering from rectal prolapse is improved when ventral
      rectopexy is performed compared with other operative or medical therapies.

PMID- 25869650
TI  - Postoperative electrolyte management: Current practice patterns of surgeons and
      residents.
AB  - BACKGROUND: Managing postoperative electrolyte imbalances often is driven by
      dogma. To identify areas of improvement, we assessed the practice pattern of
      postoperative electrolyte management among surgeons and residents. STUDY DESIGN:
      An online survey was distributed among attending surgeons and surgical residents
      at the University of Toronto. The survey was designed according to a systematic
      approach for formulating self-administered questionnaires. Questions addressed
      workload, decision making in hypothetical clinical scenarios, and improvement
      strategies. RESULTS: Of 232 surveys distributed, 156 were completed (response
      rate: 67%). The majority stated that junior residents were responsible for
      managing electrolytes at 13 University of Toronto-affiliated hospitals.
      Supervision was carried out predominately by senior residents (75%). Thirteen
      percent reported management went unsupervised. Approximately 59% of residents
      were unaware how often attending surgeons assessed patients' electrolytes.
      Despite the majority of residents (53.7%) reporting they were never given tools
      or trained in electrolyte replacement, they considered themselves moderately or
      extremely confident. The management of hypothetical clinical scenarios differed
      between residents and attending surgeons. The majority (50.5%) of respondents
      considered that an electrolyte replacement protocol is the most appropriate
      improvement strategy. CONCLUSION: Electrolyte replacement represents an important
      component of surgeons' workload. Despite reporting that formal training in
      electrolyte management is limited, residents consider themselves competent;
      however, their practice is highly variable and often differs from pharmacologic
      directed recommendations. Optimizing how postoperative electrolytes are managed
      in surgical wards requires building a framework that improves knowledge,
      training, and limits unnecessary interventions.

PMID- 25869647
TI  - Tools for Anopheles gambiae Transgenesis.
AB  - Transgenesis is an essential tool to investigate gene function and to introduce
      desired characters in laboratory organisms. Setting-up transgenesis in non-model
      organisms is challenging due to the diversity of biological life traits and due
      to knowledge gaps in genomic information. Some procedures will be broadly
      applicable to many organisms, and others have to be specifically developed for
      the target species. Transgenesis in disease vector mosquitoes has existed since
      the 2000s but has remained limited by the delicate biology of these insects.
      Here, we report a compilation of the transgenesis tools that we have designed for
      the malaria vector Anopheles gambiae, including new docking strains, convenient
      transgenesis plasmids, a puromycin resistance selection marker, mosquitoes
      expressing cre recombinase, and various reporter lines defining the activity of
      cloned promoters. This toolbox contributed to rendering transgenesis routine in
      this species and is now enabling the development of increasingly refined genetic
      manipulations such as targeted mutagenesis. Some of the reagents and procedures
      reported here are easily transferable to other nonmodel species, including other
      disease vector or agricultural pest insects. 

PMID- 25869651
TI  - Solvent-driven interactions between hydrophobically-coated nanoparticles.
AB  - Interaction between hydrophobically-coated gold nanoparticles suspended in oil is
      usually described as the combination of strong attractive van der Waals
      attraction between the gold cores and interaction between the ligands. The latter
      interaction is expected to be purely repulsive if the suspending medium is a good
      solvent for the ligands or partially attractive for a bad solvent. By measuring
      the structure factor of interacting gold nanoparticles in various solvents, we
      show that the chemical affinity of the ligand with the solvent is not the only
      parameter that controls the interaction between the ligands and that the solvent
      conformation (small rigid or long flexible molecules) also plays a crucial role.
      Gold nanoparticles covered with hexanethiol or dodecanethiol thus undergo a
      larger attraction in n-dodecane or n-hexadecane compared to toluene or
      cyclohexane. As a consequence, self-assembly of these nanoparticles into
      superlattices appears at a much lower volume fraction than predicted in n
      hexadecane or n-dodecane. Analogy with the behavior of polymer grafted colloids
      in a polymer melt is proposed to explain these unexpected results. 

PMID- 25869652
TI  - The Arabidopsis MYB96 Transcription Factor Is a Positive Regulator of ABSCISIC
      ACID-INSENSITIVE4 in the Control of Seed Germination.
AB  - Seed germination is a key developmental transition that initiates the plant life
      cycle. The timing of germination is determined by the coordinated action of two
      phytohormones, gibberellin and abscisic acid (ABA). In particular, ABA plays a
      key role in integrating environmental information and inhibiting the germination
      process. The utilization of embryonic lipid reserves contributes to seed
      germination by acting as an energy source, and ABA suppresses lipid degradation
      to modulate the germination process. Here, we report that the ABA-responsive R2R3
      type MYB transcription factor MYB96, which is highly expressed in embryo,
      regulates seed germination by controlling the expression of abscisic acid
      insensitive4 (ABI4) in Arabidopsis (Arabidopsis thaliana). In the presence of
      ABA, germination was accelerated in MYB96-deficient myb96-1 seeds, whereas the
      process was significantly delayed in MYB96-overexpressing activation-tagging
      myb96-ox seeds. Consistently, myb96-1 seeds degraded a larger extent of lipid
      reserves even in the presence of ABA, while reduced lipid mobilization was
      observed in myb96-ox seeds. MYB96 directly regulates ABI4, which acts as a
      repressor of lipid breakdown, to define its spatial and temporal expression.
      Genetic analysis further demonstrated that ABI4 is epistatic to MYB96 in the
      control of seed germination. Taken together, the MYB96-ABI4 module regulates
      lipid mobilization specifically in the embryo to ensure proper seed germination
      under suboptimal conditions.

PMID- 25869653
TI  - Examining the Causes and Consequences of Context-Specific Differential DNA
      Methylation in Maize.
AB  - DNA methylation is a stable modification of chromatin that can contribute to
      epigenetic variation through the regulation of genes or transposons. Profiling of
      DNA methylation in five maize (Zea mays) inbred lines found that while DNA
      methylation levels for more than 99% of the analyzed genomic regions are similar,
      there are still 5,000 to 20,000 context-specific differentially methylated
      regions (DMRs) between any two genotypes. The analysis of identical-by-state
      genomic regions that have limited genetic variation provided evidence that DMRs
      can occur without local sequence variation, but they are less common than in
      regions with genetic variation. Characterization of the sequence specificity of
      DMRs, location of DMRs relative to genes and transposons, and patterns of DNA
      methylation in regions flanking DMRs reveals a distinct subset of DMRs.
      Transcriptome profiling of the same tissue revealed that only approximately 20%
      of genes with qualitative (on-off) differences in gene expression are associated
      with DMRs, and there is little evidence for association of DMRs with genes that
      show quantitative differences in gene expression. We also identify a set of genes
      that may represent cryptic information that is silenced by DNA methylation in the
      reference B73 genome. Many of these genes exhibit natural variation in other
      genotypes, suggesting the potential for selection to act upon existing epigenetic
      natural variation. This study provides insights into the origin and influences of
      DMRs in a crop species with a complex genome organization. 

PMID- 25869654
TI  - The presence of fucogalactoxyloglucan and its synthesis in rice indicates
      conserved functional importance in plants.
AB  - The predominant structure of the hemicellulose xyloglucan (XyG) found in the cell
      walls of dicots is a fucogalactoXyG with an XXXG core motif, whereas in the
      Poaceae (grasses and cereals), the structure of XyG is less xylosylated (XXGGn
      core motif) and lacks fucosyl residues. However, specialized tissues of rice
      (Oryza sativa) also contain fucogalactoXyG. Orthologous genes of the
      fucogalactoXyG biosynthetic machinery of Arabidopsis (Arabidopsis thaliana) are
      present in the rice genome. Expression of these rice genes, including fucosyl-,
      galactosyl-, and acetyltransferases, in the corresponding Arabidopsis mutants
      confirmed their activity and substrate specificity, indicating that plants in the
      Poaceae family have the ability to synthesize fucogalactoXyG in vivo. The data
      presented here provide support for a functional conservation of XyG structure in
      higher plants. 

PMID- 25869656
TI  - Electrochemistry at highly oriented pyrolytic graphite (HOPG): lower limit for
      the kinetics of outer-sphere redox processes and general implications for
      electron transfer models.
AB  - The electron transfer (ET) kinetics of three redox couples in aqueous solution,
      IrCl6(2-/3-), Ru(NH3)6(3+/2+) and Fe(CN)6(4-/3-), on different grades of highly
      oriented pyrolytic graphite (HOPG) have been investigated in a droplet-cell
      setup. This simple configuration allows measurements to be made on a very short
      time scale after cleavage of HOPG, so as to minimise possible effects from
      (atmospheric) contamination, and with minimal, if any, change to the HOPG
      surface. However, the droplet-cell geometry differs from more conventional
      electrochemical setups and is more prone to ohmic drop effects. The magnitude of
      ohmic drop is elucidated by modelling the electric field in a typical droplet
      configuration. These simulations enable ohmic effects to be minimised practically
      by optimising the positions of the counter and reference electrodes in the
      droplet, and by using a concentration ratio of electrolyte to redox species that
      is higher than used conventionally. It is shown that the ET kinetics for all of
      the redox species studied herein is fast on all grades of HOPG and lower limits
      for ET rate constants are deduced. For IrCl6(2-/3-) and Fe(CN)6(4-/3-), ET on
      HOPG is at least as fast as on Pt electrodes, and for Ru(NH3)6(3+/2+) ET kinetics
      on HOPG is comparable to Pt electrodes. Given the considerable difference in the
      density of electronic states (DOS) between graphite and metal electrodes, the
      results tend to suggest that the DOS of the electrode does not play an important
      role in the ET kinetics of these outer-sphere redox couples over the range of
      values encompassing HOPG and metals. This can be rationalised because the DOS of
      all of these different electrode materials is orders of magnitude larger than
      those of the redox species in solution, so that with strong electronic coupling
      between the redox couple and electrode (adiabatic electron transfer) the
      electronic structure of the electrode becomes a relatively unimportant factor in
      the ET kinetics. 

PMID- 25869655
TI  - N-cadherin-based adherens junction regulates the maintenance, proliferation, and
      differentiation of neural progenitor cells during development.
AB  - This review addresses our current understanding of the regulatory mechanism by
      which N-cadherin, a classical cadherin, affects neural progenitor cells (NPCs)
      during development. N-cadherin is responsible for the integrity of adherens
      junctions (AJs), which develop in the sub-apical region of NPCs in the neural
      tube and brain cortex. The apical domain, which contains the sub-apical region,
      is involved in the switching from symmetric proliferative division to asymmetric
      neurogenic division of NPCs. In addition, N-cadherin-based AJ is deeply involved
      in the apico-basal polarity of NPCs and the regulation of Wnt-beta-catenin,
      hedgehog (Hh), and Notch signaling. In this review, we discuss the roles of N
      cadherin in the maintenance, proliferation, and differentiation of NPCs through
      components of AJ, beta-catenin and alphaE-catenin. 

PMID- 25869657
TI  - Production and characterization of monospecific and bispecific antibodies against
      dengue virus NS1 protein.
AB  - Dengue is a mosquito borne infection, which in recent years has become a major
      international public health concern. Annually, 100 million dengue virus
      infections are reported worldwide. The nonstructural protein 1 (NS1) of dengue
      virus is a useful target for diagnostics of dengue infection since the protein is
      abundantly circulating in the blood during acute phase of the disease, in both
      primary and secondary infections. This research paper highlights the development
      of a panel of Mab and bsMab for dengue NS1 detection. The P148 series of Mabs
      showed high specificity for recombinant dengue NS1 antigen. These antibodies
      showed no cross reactivity with recombinant dengue envelope protein and other
      viral proteins. The hybrid-hybridoma approach to generate the P156.1 and P156.2
      bsMabs from the P148 monoclonal antibody method was used during this study.
      Furthermore, the affinity purification provided good yields of quadromas
      associated with HRPO in two steps. Direct detection method involved coating of
      plates with different concentrations of recombinant antigen and detecting with
      bsMab. Sensitive sandwich assay with Mabs and bsMabs was also done. Detection of
      nonstructural dengue antigens may be of benefit for early and rapid diagnosis of
      dengue infection due to their long half-life in the blood. 

PMID- 25869658
TI  - Feasibility and Safety of Intradialysis Yoga and Education in Maintenance
      Hemodialysis Patients.
AB  - OBJECTIVE: Patients with end-stage renal disease on maintenance hemodialysis are
      much more sedentary than healthy individuals. The purpose of this study was to
      assess the feasibility and safety of a 12-week intradialysis yoga intervention
      versus a kidney education intervention on the promotion of physical activity.
      DESIGN AND METHODS: We randomized participants by dialysis shift to either 12
      week intradialysis yoga or an educational intervention. Intradialysis yoga was
      provided by yoga teachers to participants while receiving hemodialysis.
      Participants receiving the 12-week educational intervention received a
      modification of a previously developed comprehensive educational program for
      patients with kidney disease (Kidney School). The primary outcome for this study
      was feasibility based on recruitment and adherence to the interventions and
      safety of intradialysis yoga. Secondary outcomes were to determine the
      feasibility of administering questionnaires at baseline and 12 weeks including
      the Kidney Disease-Related Quality of Life-36. RESULTS: Among 56 eligible
      patients who approached for the study, 31 (55%) were interested and consented to
      participation, with 18 assigned to intradialysis yoga and 13 to the educational
      program. A total of 5 participants withdrew from the pilot study, all from the
      intradialysis yoga group. Two of these participants reported no further interest
      in participation. Three withdrawn participants switched dialysis times and
      therefore could no longer receive intradialysis yoga. As a result, 13 of 18 (72%)
      and 13 of 13 (100%) participants completed 12-week intradialysis yoga and
      educational programs, respectively. There were no adverse events related to
      intradialysis yoga. Intervention participants practiced yoga for a median of 21
      sessions (70% participation frequency), with 60% of participants practicing at
      least 2 times a week. Participants in the educational program completed a median
      of 30 sessions (83% participation frequency). Of participants who completed the
      study (n = 26), baseline and 12-week questionnaires were obtained from 85%.
      CONCLUSIONS: Our pilot study of 12-week intradialysis yoga and 12-week
      educational intervention reached recruitment goals but with less than targeted
      completion and adherence to intervention rates. This study provided valuable
      feasibility data to increase follow-up and adherence for future clinical trials
      to compare efficacy.

PMID- 25869660
TI  - Dyche Mullins: Finding filaments at the fringes.

PMID- 25869659
TI  - Vaccinia Virus Infection Requires Maturation of Macropinosomes.
AB  - The prototypic poxvirus, vaccinia virus (VACV), occurs in two infectious forms,
      mature virions (MVs) and extracellular virions (EVs). Both enter HeLa cells by
      inducing macropinocytic uptake. Using confocal microscopy, live-cell imaging,
      targeted RNAi screening and perturbants of endosome maturation, we analyzed the
      properties and maturation pathway of the macropinocytic vacuoles containing VACV
      MVs in HeLa cells. The vacuoles first acquired markers of early endosomes [Rab5,
      early endosome antigen 1 and phosphatidylinositol(3)P]. Prior to release of virus
      cores into the cytoplasm, they contained markers of late endosomes and lysosomes
      (Rab7a, lysosome-associated membrane protein 1 and sorting nexin 3). RNAi
      screening of endocytic cell factors emphasized the importance of late
      compartments for VACV infection. Follow-up perturbation analysis showed that
      infection required Rab7a and PIKfyve, confirming that VACV is a late-penetrating
      virus dependent on macropinosome maturation. VACV EV infection was inhibited by
      depletion of many of the same factors, indicating that both infectious particle
      forms share the need for late vacuolar conditions for penetration. 

PMID- 25869661
TI  - Thinking big with small molecules.
AB  - Synthetic chemistry has enabled scientists to explore the frontiers of cell
      biology, limited only by the laws of chemical bonding and reactivity. As we
      investigate biological questions of increasing complexity, new chemical
      technologies can provide systems-level views of cellular function. Here we
      discuss some of the molecular probes that illustrate this shift from a "one
      compound, one gene" paradigm to a more integrated approach to cell biology. 

PMID- 25869662
TI  - A small part of myosin IIB takes on a big role in cell polarity.
AB  - A migrating cell must establish front-to-back polarity in order to move. In this
      issue, Juanes-Garcia et al. (2015. J. Cell Biol.
      http://dx.doi.org/10.1083/jcb.201407059) report that a short serine-rich motif in
      nonmuscle myosin IIB is required to establish the cell's rear. This motif
      represents a new paradigm for what determines directional cell migration. 

PMID- 25869663
TI  - Recent insights into the cellular biology of atherosclerosis.
AB  - Atherosclerosis occurs in the subendothelial space (intima) of medium-sized
      arteries at regions of disturbed blood flow and is triggered by an interplay
      between endothelial dysfunction and subendothelial lipoprotein retention. Over
      time, this process stimulates a nonresolving inflammatory response that can cause
      intimal destruction, arterial thrombosis, and end-organ ischemia. Recent advances
      highlight important cell biological atherogenic processes, including
      mechanotransduction and inflammatory processes in endothelial cells, origins and
      contributions of lesional macrophages, and origins and phenotypic switching of
      lesional smooth muscle cells. These advances illustrate how in-depth mechanistic
      knowledge of the cellular pathobiology of atherosclerosis can lead to new ideas
      for therapy. 

PMID- 25869664
TI  - A regulatory motif in nonmuscle myosin II-B regulates its role in migratory front
      back polarity.
AB  - In this study, we show that the role of nonmuscle myosin II (NMII)-B in front
      back migratory cell polarity is controlled by a short stretch of amino acids
      containing five serines (1935-1941). This motif resides near the junction between
      the C terminus helical and nonhelical tail domains. Removal of this motif
      inhibited NMII-B assembly, whereas its insertion into NMII-A endowed an NMII-B
      like ability to generate large actomyosin bundles that determine the rear of the
      cell. Phosphomimetic mutation of the five serines also inhibited NMII-B assembly,
      rendering it unable to support front-back polarization. Mass spectrometric
      analysis showed that several of these serines are phosphorylated in live cells.
      Single-site mutagenesis showed that serine 1935 is a major regulatory site of
      NMII-B function. These data reveal a novel regulatory mechanism of NMII in
      polarized migrating cells by identifying a key molecular determinant that confers
      NMII isoform functional specificity. 

PMID- 25869665
TI  - Excision of translesion synthesis errors orchestrates responses to helix
      distorting DNA lesions.
AB  - In addition to correcting mispaired nucleotides, DNA mismatch repair (MMR)
      proteins have been implicated in mutagenic, cell cycle, and apoptotic responses
      to agents that induce structurally aberrant nucleotide lesions. Here, we
      investigated the mechanistic basis for these responses by exposing cell lines
      with single or combined genetic defects in nucleotide excision repair (NER),
      postreplicative translesion synthesis (TLS), and MMR to low-dose ultraviolet
      light during S phase. Our data reveal that the MMR heterodimer Msh2/Msh6 mediates
      the excision of incorrect nucleotides that are incorporated by TLS opposite helix
      distorting, noninstructive DNA photolesions. The resulting single-stranded DNA
      patches induce canonical Rpa-Atr-Chk1-mediated checkpoints and, in the next cell
      cycle, collapse to double-stranded DNA breaks that trigger apoptosis. In
      conclusion, a novel MMR-related DNA excision repair pathway controls TLS a
      posteriori, while initiating cellular responses to environmentally relevant
      densities of genotoxic lesions. These results may provide a rationale for the
      colorectal cancer tropism in Lynch syndrome, which is caused by inherited MMR
      gene defects. 

PMID- 25869666
TI  - Microtubule minus end motors kinesin-14 and dynein drive nuclear congression in
      parallel pathways.
AB  - Microtubules (MTs) and associated motors play a central role in nuclear
      migration, which is crucial for diverse biological functions including cell
      division, polarity, and sexual reproduction. In this paper, we report a dual
      mechanism underlying nuclear congression during fission yeast karyogamy upon
      mating of haploid cells. Using microfluidic chambers for long-term imaging, we
      captured the precise timing of nuclear congression and identified two minus end
      directed motors operating in parallel in this process. Kinesin-14 Klp2 associated
      with MTs may cross-link and slide antiparallel MTs emanating from the two nuclei,
      whereas dynein accumulating at spindle pole bodies (SPBs) may pull MTs nucleated
      from the opposite SPB. Klp2-dependent nuclear congression proceeds at constant
      speed, whereas dynein accumulation results in an increase of nuclear velocity
      over time. Surprisingly, the light intermediate chain Dli1, but not dynactin, is
      required for this previously unknown function of dynein. We conclude that
      efficient nuclear congression depends on the cooperation of two minus end
      directed motors. 

PMID- 25869667
TI  - A role for disulfide bonding in keratin intermediate filament organization and
      dynamics in skin keratinocytes.
AB  - We recently reported that a trans-dimer, homotypic disulfide bond involving
      Cys367 in keratin 14 (K14) occurs in an atomic-resolution structure of the
      interacting K5/K14 2B domains and in keratinocyte cell lines. Here we show that a
      sizable fraction of the K14 and K5 protein pools participates in interkeratin
      disulfide bonding in primary cultures of mouse skin keratinocytes. By comparing
      the properties of wild-type K14 with a completely cysteine-free variant thereof,
      we found that K14-dependent disulfide bonding limited filament elongation during
      polymerization in vitro but was necessary for the genesis of a perinuclear
      concentrated network of keratin filaments, normal keratin cycling, and the
      sessile behavior of the nucleus and whole cell in keratinocytes studied by live
      imaging. Many of these phenotypes were rescued when analyzing a K14 variant
      harboring a single Cys residue at position 367. These findings establish
      disulfide bonding as a novel and important mechanism regulating the assembly,
      intracellular organization, and dynamics of K14-containing intermediate filaments
      in skin keratinocytes. 

PMID- 25869668
TI  - Sac2/INPP5F is an inositol 4-phosphatase that functions in the endocytic pathway.
AB  - The recruitment of inositol phosphatases to endocytic membranes mediates
      dephosphorylation of PI(4,5)P2, a phosphoinositide concentrated in the plasma
      membrane, and prevents its accumulation on endosomes. The importance of the
      conversion of PI(4,5)P2 to PtdIns during endocytosis is demonstrated by the
      presence of both a 5-phosphatase and a 4-phosphatase (Sac domain) module in the
      synaptojanins, endocytic PI(4,5)P2 phosphatases conserved from yeast to humans
      and the only PI(4,5)P2 phosphatases in yeast. OCRL, another 5-phosphatase that
      couples endocytosis to PI(4,5)P2 dephosphorylation, lacks a Sac domain. Here we
      show that Sac2/INPP5F is a PI4P phosphatase that colocalizes with OCRL on
      endocytic membranes, including vesicles formed by clathrin-mediated endocytosis,
      macropinosomes, and Rab5 endosomes. An OCRL-Sac2/INPP5F interaction could be
      demonstrated by coimmunoprecipitation and was potentiated by Rab5, whose activity
      is required to recruit Sac2/INPP5F to endosomes. Sac2/INPP5F and OCRL may
      cooperate in the sequential dephosphorylation of PI(4,5)P2 at the 5 and 4
      position of inositol in a partnership that mimics that of the two phosphatase
      modules of synaptojanin. 

PMID- 25869669
TI  - Spatiotemporal control of phosphatidylinositol 4-phosphate by Sac2 regulates
      endocytic recycling.
AB  - It is well established that the spatial- and temporal-restricted generation and
      turnover of phosphoinositides (PIs) by a cascade of PI-metabolizing enzymes is a
      key regulatory mechanism in the endocytic pathway. Here, we demonstrate that the
      Sac1 domain-containing protein Sac2 is a PI 4-phosphatase that specifically
      hydrolyzes phosphatidylinositol 4-phosphate in vitro. We further show that Sac2
      colocalizes with early endosomal markers and is recruited to transferrin (Tfn)
      containing vesicles during endocytic recycling. Exogenous expression of the
      catalytically inactive mutant Sac2C458S resulted in altered cellular distribution
      of Tfn receptors and delayed Tfn recycling. Furthermore, genomic ablation of Sac2
      caused a similar perturbation on Tfn and integrin recycling as well as defects in
      cell migration. Structural characterization of Sac2 revealed a unique pleckstrin
      like homology Sac2 domain conserved in all Sac2 orthologues. Collectively, our
      findings provide evidence for the tight regulation of PIs by Sac2 in the
      endocytic recycling pathway. 

PMID- 25869672
TI  - A visual volumetric hydrogel sensor enables quantitative and sensitive detection
      of copper ions.
AB  - We propose a visual volumetric sensor with 5,6-dicarboxylic fluorescein cross
      linked amine-functionalized polyacrylamide hydrogel. The sensor undergoes volume
      response to Cu(2+) ions at the MUM level, which enables naked-eye quantitative
      detection by reading the graduation on a pipette. 

PMID- 25869670
TI  - TMEM231, mutated in orofaciodigital and Meckel syndromes, organizes the ciliary
      transition zone.
AB  - The Meckel syndrome (MKS) complex functions at the transition zone, located
      between the basal body and axoneme, to regulate the localization of ciliary
      membrane proteins. We investigated the role of Tmem231, a two-pass transmembrane
      protein, in MKS complex formation and function. Consistent with a role in
      transition zone function, mutation of mouse Tmem231 disrupts the localization of
      proteins including Arl13b and Inpp5e to cilia, resulting in phenotypes
      characteristic of MKS such as polydactyly and kidney cysts. Tmem231 and B9d1 are
      essential for each other and other complex components such as Mks1 to localize to
      the transition zone. As in mouse, the Caenorhabditis elegans orthologue of
      Tmem231 localizes to and controls transition zone formation and function,
      suggesting an evolutionarily conserved role for Tmem231. We identified TMEM231
      mutations in orofaciodigital syndrome type 3 (OFD3) and MKS patients that
      compromise transition zone function. Thus, Tmem231 is critical for organizing the
      MKS complex and controlling ciliary composition, defects in which cause OFD3 and
      MKS. 

PMID- 25869671
TI  - TAGLN2 regulates T cell activation by stabilizing the actin cytoskeleton at the
      immunological synapse.
AB  - The formation of an immunological synapse (IS) requires tight regulation of actin
      dynamics by many actin polymerizing/depolymerizing proteins. However, the
      significance of actin stabilization at the IS remains largely unknown. In this
      paper, we identify a novel function of TAGLN2--an actin-binding protein
      predominantly expressed in T cells--in stabilizing cortical F-actin, thereby
      maintaining F-actin contents at the IS and acquiring LFA-1 (leukocyte function
      associated antigen-1) activation after T cell receptor stimulation. TAGLN2 blocks
      actin depolymerization and competes with cofilin both in vitro and in vivo.
      Knockout of TAGLN2 (TAGLN2(-/-)) reduced F-actin content and destabilized F-actin
      ring formation, resulting in decreased cell adhesion and spreading. TAGLN2(-/-) T
      cells displayed weakened cytokine production and cytotoxic effector function.
      These findings reveal a novel function of TAGLN2 in enhancing T cell responses by
      controlling actin stability at the IS.

PMID- 25869673
TI  - New horizons in platelet research: understanding and harnessing platelet
      functional diversity.
AB  - Recent years have been ripe with discoveries of non-haemostatic platelet
      functions. This led to the appreciation of the significant, previously unknown,
      role played by the platelets in various pathologies and regenerative processes.
      As a result, exciting opportunities for clinical applications in fields as
      diverse as regenerative medicine and cancer treatment are emerging. However,
      their realization depends on the understanding of the regulatory mechanisms
      governing these diverse platelet functions, so that particular platelet responses
      could be artificially tailored to specific clinical situations. Current
      understanding of the signalling pathways controlling haemostatic responses is
      rooted in the development of quantitative assays for measuring them and sensitive
      markers for their quantification. However, the existing assays and markers are
      not sufficiently sensitive for distinguishing between individual signalling
      pathways and unravelling inter-pathway connections. Moreover, entirely new
      approaches are needed for studying non-haemostatic platelet functions, since
      there are currently no assays or markers for quantifying them. We review the on
      going efforts in these directions, including our own recent work on using lectins
      as sensitive probes for profiling platelet activation.

PMID- 25869674
TI  - Calculating integral dose using data exported from a commercial record and verify
      system.
AB  - Integral dose has been useful in investigations into the incidence of second
      primary malignancies in radiotherapy patients. This note outlines an approach to
      calculation of integral dose for a group of prostate patients using only data
      exported from a commercial record and verify system. Even though it was necessary
      to make some assumptions about patient anatomy, comparison with integral dose
      calculated from data exported from the planning system showed good agreement. 

PMID- 25869675
TI  - Sensible method for updating motif instances in an increased biological network.
AB  - A network motif is defined as an over-represented subgraph pattern in a network.
      Network motif based techniques have been widely applied in analyses of biological
      networks such as transcription regulation networks (TRNs), protein-protein
      interaction networks (PPIs), and metabolic networks. The detection of network
      motifs involves the computationally expensive enumeration of subgraphs, NP
      complete graph isomorphism testing, and significance testing through the
      generation of many random graphs to determine the statistical uniqueness of a
      given subgraph. These computational obstacles make network motif analysis
      unfeasible for many real-world applications. We observe that the fast growth of
      biotechnology has led to the rapid accretion of molecules (vertices) and
      interactions (edges) to existing biological network databases. Even with a small
      percentage of additions, revised networks can have a large number of differing
      motif instances. Currently, no existing algorithms recalculate motif instances in
      'updated' networks in a practical manner. In this paper, we introduce a sensible
      method for efficiently recalculating motif instances by performing motif
      enumeration from only updated vertices and edges. Preliminary experimental
      results indicate that our method greatly reduces computational time by
      eliminating the repeated enumeration of overlapped subgraph instances detected in
      earlier versions of the network. The software program implementing this
      algorithm, defined as SUNMI (Sensible Update of Network Motif Instances), is
      currently a stand-alone java program and we plan to upgrade it as a web
      interactive program that will be available through
      http://faculty.washington.edu/kimw6/research.htm in near future. Meanwhile it is
      recommended to contact authors to obtain the stand-alone SUNMI program. 

PMID- 25869676
TI  - A faith in the coherence of the living world.
AB  - In this review, I compare the development of Monod's intellectual leadership in
      two fields, the regulation of enzyme biosynthesis and the control of enzymatic
      activity. I characterize the comings and goings between his scrupulous analysis
      of a given model system, his ability to compare the outcome with very distant
      experimental results, his audacity in formulating, then a physical interpretation
      of this convergence through a unifying mechanism. Finally, I briefly discuss how
      his attitude has durably impacted the whole field of molecular biology. 

PMID- 25869677
TI  - ZAK induces cardiomyocyte hypertrophy and brain natriuretic peptide expression
      via p38/JNK signaling and GATA4/c-Jun transcriptional factor activation.
AB  - Cardiomyocyte hypertrophy is an adaptive response of heart to various stress
      conditions. During the period of stress accumulation, transition from
      physiological hypertrophy to pathological hypertrophy results in the promotion of
      heart failure. Our previous studies found that ZAK, a sterile alpha motif and
      leucine zipper containing kinase, was highly expressed in infarcted human hearts
      and demonstrated that overexpression of ZAK induced cardiac hypertrophy. This
      study evaluates, cellular events associated with the expression of two
      doxycycline (Dox) inducible Tet-on ZAK expression systems, a Tet-on ZAK WT (wild
      type), and a Tet-on ZAK DN (mutant, Dominant-negative form) in H9c2 myoblast
      cells; Tet-on ZAK WT was found to increase cell size and hypertrophic marker BNP
      in a dose-dependent manner. To ascertain the mechanism of ZAK-mediated
      hypertrophy, expression analysis with various inhibitors of the related upstream
      and downstream proteins was performed. Tet-on ZAK WT expression triggered the p38
      and JNK pathway and also activated the expression and nuclear translocation of p
      GATA4 and p-c-Jun transcription factors, without the involvement of p-ERK or
      NFATc3. However, Tet-on ZAK DN showed no effect on the p38 and JNK signaling
      cascade. The results showed that the inhibitors of JNK1/2 and p38 significantly
      suppressed ZAK-induced BNP expression. The results show the role of ZAK and/or
      the ZAK downstream events such as JNK and p38 phosphorylation, c-Jun, and GATA-4
      nuclear translocation in cardiac hypertrophy. ZAK and/or the ZAK downstream p38,
      and JNK pathway could therefore be potential targets to ameliorate cardiac
      hypertrophy symptoms in ZAK-overexpressed patients.

PMID- 25869678
TI  - Effect of amino acid substitution in the staphylococcal peptides warnericin RK
      and PSMalpha on their anti-Legionella and hemolytic activities.
AB  - Warnericin RK from Staphylococcus warneri and PSMalpha from Staphylococcus
      epidermidis are anti-Legionella peptides which were differently classified in a
      previous study according to their mode of action. Indeed, warnericin RK is highly
      hemolytic with a bactericidal mode of action, whereas PSMalpha is poorly
      hemolytic with a bacteriostatic mode of action toward L. pneumophila. In order to
      find anti-Legionella peptides which are not hemolytic, a collection of peptides
      varying in sequence from warnericin RK to PSMalpha were designed and synthesized,
      and their anti-Legionella activities, in terms of growth inhibition,
      permeabilization, and bactericidal effect, as well as their hemolytic activities,
      were measured and compared. The results showed that some residues, at position 14
      for both peptides for instance, were of major importance for bactericidal and
      hemolytic activities. 

PMID- 25869679
TI  - The ALERT scale: an observational study of early prediction of adverse hospital
      outcome for medical patients.
AB  - OBJECTIVES: Some medical patients are at greater risk of adverse outcomes than
      others and may benefit from higher observation hospital units. We constructed and
      validated a model predicting adverse hospital outcome for patients. Study results
      may be used to admit patients into planned tiered care units. Adverse outcome
      comprised death or cardiac arrest during the first 30 days of hospitalisation, or
      transfer to intensive care within the first 48 h of admission. SETTING: The study
      took place at two tertiary teaching hospitals and two community hospitals in
      Winnipeg, Manitoba, Canada. PARTICIPANTS: We analysed data from 4883 consecutive
      admissions at a tertiary teaching hospital to construct the Early Prediction of
      Adverse Hospital Outcome for Medical Patients (ALERT) model using logistic
      regression. Robustness of the model was assessed through validation performed
      across four hospitals over two time periods, including 65,640 consecutive
      admissions. OUTCOME: Receiver-operating characteristic curves (ROC) and
      sensitivity and specificity analyses were used to assess the usefulness of the
      model. RESULTS: 9.3% of admitted patients experienced adverse outcomes. The final
      model included gender, age, Charlson Comorbidity Index, Activities of Daily
      Living Score, Glasgow Coma Score, systolic blood pressure, respiratory rate,
      heart rate and white cell count. The model was discriminative (ROC=0.83) in
      predicting adverse outcome. ALERT accurately predicted 75% of the adverse
      outcomes (sensitivity) and 75% of the non-adverse outcomes (specificity).
      Applying the same model to each validation hospital and time period produced
      similar accuracy and discrimination to that in the development hospital.
      CONCLUSIONS: Used during initial assessment of patients admitted to general
      medical wards, the ALERT scale may complement other assessment measures to better
      screen patients. Those considered as higher risk by the ALERT scale may then be
      provided more effective care from action such as planned tiered care units.

PMID- 25869681
TI  - Correction. The contribution of primary prevention medication and dietary change
      in coronary mortality reduction in England between 2000 and 2007: a modelling
      study.

PMID- 25869680
TI  - Evidence for a persistent, major excess in all cause admissions to hospital in
      children with type-1 diabetes: results from a large Welsh national matched
      community cohort study.
AB  - OBJECTIVES: To estimate the excess in admissions associated with type1 diabetes
      in childhood. DESIGN: Matched-cohort study using anonymously linked hospital
      admission data. SETTING: Brecon Group Register of new cases of childhood diabetes
      in Wales linked to hospital admissions data within the Secure Anonymised
      Information Linkage Databank. POPULATION: 1577 Welsh children (aged between 0 and
      15 years) from the Brecon Group Register with newly-diagnosed type-1 diabetes
      between 1999-2009 and 7800 population controls matched on age, sex, county, and
      deprivation, randomly selected from the local population. MAIN OUTCOME MEASURES:
      Difference in all-cause hospital admission rates, 30-days post-diagnosis until 31
      May 2012, between participants and controls. RESULTS: Children with type-1
      diabetes were followed up for a total of 12,102 person years and were at 480%
      (incidence rate ratios, IRR 5.789, (95% CI 5.34 to 6.723), p<0.0001) increased
      risk of hospital admission in comparison to matched controls. The highest
      absolute excess of admission was in the age group of 0-5 years, with a 15.4% (IRR
      0.846, (95% CI 0.744 to 0.965), p=0.0061) reduction in hospital admissions for
      every 5-year increase in age at diagnosis. A trend of increasing admission rates
      in lower socioeconomic status groups was also observed, but there was no evidence
      of a differential rate of admissions between men and women when adjusted for
      background risk. Those receiving outpatient care at large centres had a 16.1%
      (IRR 0.839, (95% CI 0.709 to 0.990), p=0.0189) reduction in hospital admissions
      compared with those treated at small centres. CONCLUSIONS: There is a large
      excess of hospital admissions in paediatric patients with type-1 diabetes. Rates
      are highest in the youngest children with low socioeconomic status. Factors
      influencing higher admission rates in smaller centres (eg, "out of hours
      resources") need to be explored with the aim of targeting modifiable influences
      on admission rates.

PMID- 25869682
TI  - Fitness for purpose study of the Field Assessment Conditioning Tool (FACT): a
      research protocol.
AB  - INTRODUCTION: As part of a programme of research aiming to improve the outcomes
      of traumatically injured children, a multisource healthcare advocacy tool has
      been developed to allow trauma team members and hospital governance
      administrators to reflect and to act on complex trauma team-hospital systems
      interactions. We have termed this tool a Field Assessment Conditioning Tool
      (FACT). The FACT draws on quantitative data including clinical care points in
      addition to self-reflective qualitative data. The FACT is designed to provide
      feedback on this assessment data both horizontally across fellow potential team
      members and vertically to the hospital/organisation governance structure,
      enabling process gap identification and allowing an agenda of improvements to be
      realised. The aim of the study described in this paper is to explore the
      perceived fitness for purpose of the FACT to provide an opportunity for
      healthcare advocacy by healthcare professionals caring for traumatically injured
      children. METHODS AND ANALYSIS: The FACT will be implemented and studied in three
      district hospitals, each around a major trauma centre in the UK, USA and New
      Zealand. Using a qualitative approach with standardised semi-structured
      interviews and thematic analysis we will explore the following question: Is the
      FACT fit for purpose in terms of providing a framework to evaluate, reflect and
      act on the individual hospital's own performance (trauma team-hospital
      interactions) in terms of readiness to receive traumatically injured children?
      ETHICS AND DISSEMINATION: Ethics opinion was sought for each research host
      organisation participating and deemed not required. The results will be
      disseminated to participating sites, networks and published in high-impact
      journals.

PMID- 25869683
TI  - UK research spend in 2008 and 2012: comparing stroke, cancer, coronary heart
      disease and dementia.
AB  - OBJECTIVE: To assess UK governmental and charity research funding in 2012 for
      cancer, coronary heart disease (CHD), dementia and stroke, and to make
      comparisons with 2008 levels. DESIGN: Analysis of research expenditure. SETTING:
      United Kingdom. MAIN OUTCOME MEASURES: We identified UK governmental agencies and
      charities providing health research funding to determine the 2012 levels of
      funding for cancer, CHD, dementia and stroke. Levels of research funding were
      compared to burden of disease measures, including prevalence, disability adjusted
      life years and economic burden. RESULTS: The combined research funding into
      cancer, CHD, dementia and stroke by governmental and charity organisations in
      2012 was L856 million, of which L544 million (64%) was devoted to cancer, L166
      million (19%) to CHD, L90 million (11%) to dementia and L56 million (7%) to
      stroke. For every L10 of health and social care costs attributable to each
      disease, cancer received L1.08 in research funding, CHD L0.65, stroke L0.19 and
      dementia L0.08. A considerable shift in the distribution of government research
      funding was observed between 2008 and 2012. In 2008, 66% of governmental research
      funding into the four conditions under study was devoted to cancer, 21% to CHD,
      9% to dementia and 4% to stroke. In 2012, the proportions devoted to dementia and
      stroke had increased to 21% and 12%, respectively, with cancer accounting for 45%
      of total research spend. CONCLUSIONS: Although there has been much progress by
      government to increase levels of research funding for dementia and stroke, these
      areas remain underfunded when compared with the burden of disease.

PMID- 25869684
TI  - Estimating the change in life expectancy after a diagnosis of cancer among the
      Australian population.
AB  - OBJECTIVES: Communication of relevant prognostic information is critical in
      helping patients understand the implications of their cancer diagnosis. We
      describe measures of prognosis to help communicate relevant prognostic
      information to improve patients' understanding of the implications of their
      cancer diagnosis. SETTING: Australia-wide population-based cancer registry
      cohort. PARTICIPANTS: 870,878 patients aged 15-89 years diagnosed with invasive
      cancer between 1990 and 2007, with mortality follow-up information to December
      2010. PRIMARY AND SECONDARY OUTCOME MEASURES: Flexible parametric models were
      used to estimate loss of life expectancy (LOLE), remaining life expectancy (RLE)
      and 10-year cumulative probability of cancer-specific death (1-relative
      survival). RESULTS: On average, Australians diagnosed with cancer at age 40 years
      faced losing an average of 11.2 years of life (95% CI 11.1 to 11.4) due to their
      cancer, while those diagnosed at 80 years faced losing less, an average of 3.9
      years (3.9 to 4.0) because of higher competing mortality risks. In contrast,
      younger people had lower estimated cumulative probabilities of cancer-specific
      death within 10 years (40 years: 21.5%, 21.4% to 22.1%) compared with older
      people (80 years: 55.4%, 55.0% to 55.9%). The patterns for individual cancers
      varied widely, both by cancer type and by age within cancer type. CONCLUSIONS:
      The LOLE and RLE measures provide complementary messages to standard relative
      survival estimates (expressed here in terms of cumulative probability of cancer
      specific death). Importantly, relative survival per se underplays the greater
      absolute impact that a cancer diagnosis has at a younger age on LOLE. When
      presented in isolation for all cancers, it may provide a misleading impression of
      future mortality burden of cancer overall, and furthermore, it will obscure
      patterns of mortality by type and by age data within type. Alternative measures
      of LOLE, therefore, provide important communication about mortality risk to
      patients with cancer worldwide and should be incorporated into standard reporting
      and dissemination strategies.

PMID- 25869685
TI  - Exploring the challenges of implementing e-health: a protocol for an update of a
      systematic review of reviews.
AB  - INTRODUCTION: There is great potential for e-health to deliver cost-effective,
      quality healthcare and spending on e-health systems by governments and healthcare
      systems is increasing worldwide. However, the literature often describes
      problematic and unsuccessful attempts to implement these new technologies into
      routine clinical practice. To understand and address the challenges of
      implementing e-health, a systematic review was conducted in 2009, which
      identified several conceptual barriers and facilitators to implementation. As
      technology is rapidly changing and new e-health solutions are constantly evolving
      to meet the needs of current practice, an update of this review is deemed
      necessary to understand current challenges to the implementation of e-health.
      This research aims to identify, summarise and synthesise currently available
      evidence, by undertaking a systematic review of reviews to explore the barriers
      and facilitators to implementing e-health across a range of healthcare settings.
      METHODS AND ANALYSIS: This is a protocol for an update of a systematic review of
      reviews. We will search MEDLINE, EMBASE, CINAHL, PSYCINFO and The Cochrane
      Library for studies published between 2009 and 2014. We will check reference
      lists of included studies for further studies. Two authors will independently
      screen the titles and abstracts identified from the search; any discrepancies
      will be resolved by discussion and consensus. Full-text papers will be obtained
      and relevant reviews will be selected against inclusion criteria. Eligible
      reviews have to be based on the implementation of e-health technologies. Data
      from eligible reviews will be extracted using a data abstraction form. A thematic
      analysis of barriers and facilitators to e-health implementation will be
      conducted. ETHICS AND DISSEMINATION: Ethical approval is not required. The
      permission of the original authors to update the review was sought and granted.
      TRIAL REGISTRATION NUMBER: PROSPERO CRD42015017661.

PMID- 25869686
TI  - The effectiveness of toolkits as knowledge translation strategies for integrating
      evidence into clinical care: a systematic review.
AB  - OBJECTIVES: The aim of this systematic review was to evaluate the effectiveness
      of toolkits as a knowledge translation (KT) strategy for facilitating the
      implementation of evidence into clinical care. Toolkits include multiple
      resources for educating and/or facilitating behaviour change. DESIGN: Systematic
      review of the literature on toolkits. METHODS: A search was conducted on MEDLINE,
      EMBASE, PsycINFO and CINAHL. Studies were included if they evaluated the
      effectiveness of a toolkit to support the integration of evidence into clinical
      care, and if the KT goal(s) of the study were to inform, share knowledge, build
      awareness, change practice, change behaviour, and/or clinical outcomes in
      healthcare settings, inform policy, or to commercialise an innovation. Screening
      of studies, assessment of methodological quality and data extraction for the
      included studies were conducted by at least two reviewers. RESULTS: 39 relevant
      studies were included for full review; 8 were rated as moderate to strong
      methodologically with clinical outcomes that could be somewhat attributed to the
      toolkit. Three of the eight studies evaluated the toolkit as a single KT
      intervention, while five embedded the toolkit into a multistrategy intervention.
      Six of the eight toolkits were partially or mostly effective in changing clinical
      outcomes and six studies reported on implementation outcomes. The types of
      resources embedded within toolkits varied but included predominantly educational
      materials. CONCLUSIONS: Future toolkits should be informed by high-quality
      evidence and theory, and should be evaluated using rigorous study designs to
      explain the factors underlying their effectiveness and successful implementation.

PMID- 25869687
TI  - Chronic kidney disease as a risk factor for incident gout among men and women:
      retrospective cohort study using data from the Framingham Heart Study.
AB  - OBJECTIVES: Historically, the nature of association between chronic kidney
      disease (CKD) and gouty arthritis has been unclear. The goal of the present study
      was to test the hypothesis that CKD is an independent risk factor for developing
      incident gout. DESIGN: Patients were from the original Framingham Heart Study
      cohort. Using Cox proportional hazard models we estimated the HR of CKD to
      incident gout among men and women separately after adjusting for age, alcohol
      consumption, smoking, hypertension, diabetes and body mass index. SETTINGS:
      Patients were all from Framingham, Massachusetts, USA. PARTICIPANTS: Excluding
      patients who had CKD in the first visit from this study, 2159 men and 2558 women
      were selected covering a 54-year period (1948-2002). RESULTS: There were 371
      incident cases (231 men and 140 women) of gout over the follow-up of 140,421
      person-years. Incidence rates of gout per 1000 person-years for participants with
      and without CKD were 6.82 (95% CI 5.10 to 9.10) and 2.43 (2.18 to 2.71),
      respectively. In multivariable Cox models, CKD was associated with gout, with a
      HR of 1.88 (1.13 to 3.13) among men and 2.31 (1.25 to 4.24) among women.
      Additional analyses using alternate definitions for CKD and cross-sectional study
      did not change the results. Sensitivity analysis suggested that the observed
      findings might be an underestimate of the true relative risk. CONCLUSIONS: The
      present study provides epidemiological evidence to support the notion that CKD is
      a risk factor for gout.

PMID- 25869688
TI  - Acupuncture for acute migraine attacks in adults: a systematic review protocol.
AB  - INTRODUCTION: Acupuncture has been used worldwide for migraine attacks. This
      systematic review aims to assess if acupuncture is effective and safe in
      relieving headache, preventing relapse and reducing migraine-associated symptoms
      for the treatment of acute migraine attacks in adults. METHODS AND ANALYSIS: We
      will search the following seven databases from inception to February 2015:
      MEDLINE (OVID), EMBASE, the Cochrane Central Register of Controlled Trials
      (CENTRAL) and four Chinese databases (Chinese Biomedical Database, China National
      Knowledge Infrastructure, Chinese Science and Technology Periodical Database and
      Wanfang Database). Any randomised controlled trials in English or Chinese related
      to acupuncture for acute migraine attacks will be included. Conference abstracts
      and reference lists of included manuscripts will also be searched. The study
      inclusion, data extraction and quality assessment will be conducted independently
      by two reviewers. Meta-analysis will be performed using RevMan V.5.3.5
      statistical software. DISSEMINATION: The findings will be disseminated through
      peer-reviewed publication and/or conference presentations. TRIAL REGISTRATION
      NUMBER: PROSPERO CRD42014013352.

PMID- 25869689
TI  - Effect of glucomannan supplementation on body weight in overweight and obese
      children: protocol of a randomised controlled trial.
AB  - INTRODUCTION: Glucomannan (GNN), a water-soluble dietary fibre derived from the
      plant Amorphophallus konjac, is marketed for weight reduction. The exact
      mechanisms by which GNN might exert its actions are unclear. However, it has been
      shown that GNN slows gastric emptying by forming a viscous gel of large volume,
      which increases the feeling of satiety. Current evidence on the effectiveness of
      GNN for weight reduction is sparse, and well-designed trials performed in
      children are needed to assess the efficacy of this modality. We aim to
      systematically evaluate the efficacy of GNN consumption for the management of
      children who are overweight or obese. METHODS AND ANALYSIS: Children aged 6-17
      years who are overweight or obese (based on the WHO growth criteria) will be
      randomly assigned to receive GNN or placebo (maltodextrin) (both at a dose of 3
      g/day) for 3 months and will be followed-up for 3 months. Before the
      intervention, all children will receive dietetic advice, and they will be
      encouraged to engage in physical activity. The primary outcome measure will be
      the body mass index-for-age z-score difference between the groups at the end of
      the intervention. ETHICS AND DISSEMINATION: The study was approved by the
      Bioethics Committee of the Medical University of Warsaw. The findings of this
      trial will be submitted to a peer-reviewed journal (paediatric, nutrition or
      gastroenterology). Abstracts will be submitted to relevant national and
      international conferences. TRIAL REGISTRATION NUMBER: NCT02280772.

PMID- 25869690
TI  - Can analyses of electronic patient records be independently and externally
      validated? Study 2--the effect of beta-adrenoceptor blocker therapy on cancer
      survival: a retrospective cohort study.
AB  - OBJECTIVES: To conduct a fully independent, external validation of a research
      study based on one electronic health record database using a different database
      sampling from the same population. DESIGN: Retrospective cohort analysis of beta
      blocker therapy and all-cause mortality in patients with cancer. SETTING: Two UK
      national primary care databases (PCDs): the Clinical Practice Research Datalink
      (CPRD) and Doctors' Independent Network (DIN). PARTICIPANTS: CPRD data for 11,302
      patients with cancer compared with published results from DIN for 3462 patients;
      study period January 1997 to December 2006. PRIMARY AND SECONDARY OUTCOME
      MEASURES: All-cause mortality: overall; by treatment subgroup (beta-blockers
      only, beta-blockers plus other blood pressure lowering medicines (BPLM), other
      BPLMs only); and by cancer site. RESULTS: Using CPRD, beta-blocker use was not
      associated with mortality (HR=1.03, 95% CI 0.93 to 1.14, vs patients prescribed
      other BPLMs only), but DIN beta-blocker users had significantly higher mortality
      (HR=1.18, 95% CI 1.04 to 1.33). However, these HRs were not statistically
      different (p=0.063), but did differ for patients on beta-blockers alone
      (CPRD=0.94, 95% CI 0.82 to 1.07; DIN=1.37, 95% CI 1.16 to 1.61; p<0.001). Results
      for individual cancer sites differed by study, but only significantly for
      prostate and pancreas cancers. Results were robust under sensitivity analyses,
      but we could not be certain that mortality was identically defined in both
      databases. CONCLUSIONS: We found a complex pattern of similarities and
      differences between databases. Overall treatment effect estimates were not
      statistically different, adding to a growing body of evidence that different UK
      PCDs produce comparable effect estimates. However, individually the two studies
      lead to different conclusions regarding the safety of beta-blockers and some
      subgroup effects differed significantly. Single studies using even internally
      well-validated databases do not guarantee generalisable results, especially for
      subgroups, and confirmatory studies using at least one other independent data
      source are strongly recommended.

PMID- 25869691
TI  - Familial transmission of chronic obstructive pulmonary disease in adoptees: a
      Swedish nationwide family study.
AB  - OBJECTIVES: Familial clustering of chronic obstructive pulmonary disease (COPD)
      is well established, but the familial risk of COPD has not been determined among
      adoptees. The aim was to determine whether the familial transmission of COPD is
      related to disease in biological and/or adoptive parents. DESIGN: Historic cohort
      study. PARTICIPANTS: 80,214 (50% females). METHODS: The Swedish Multi-Generation
      Register was used to follow all Swedish-born adoptees born in 1932-2004
      (n=80,214) between 1 January 1964 and 31 December 2010 for COPD (n=1978). The
      risk of COPD was estimated in adoptees with at least one biological parent with
      COPD but no adoptive parent with COPD (n=162) compared with adoptees without a
      biological or adoptive parent with COPD. The risk of COPD was also determined in
      adoptees with at least one adoptive parent but no biological parent with COPD
      (n=110), and in adoptees with both affected biological and adoptive parents
      (n=162). PRIMARY OUTCOME MEASURE: COPD in adoptees. RESULTS: Adoptees with COPD
      in at least one biological parent but no adoptive parent were more likely to have
      COPD than adoptees without a biological or adoptive parent with COPD
      (standardised incidence ratio, SIR=1.98 (95% CI 1.69 to 2.31)). The familial SIR
      for adoptees with both a biological parent and an adoptive parent with COPD was
      1.68 (95% CI 1.39 to 2.00). Adoptees with at least one adoptive parent with COPD
      but no biological parent with COPD were not at an increased risk of COPD
      (SIR=1.12 (95% CI 0.92 to 1.35)). CONCLUSIONS: The findings of the study show
      that the familial transmission of COPD is associated with COPD in biological but
      not adoptive parents, suggesting that genetic or early life factors are important
      in the familial transmission of COPD.

PMID- 25869719
TI  - Effects of fetal head shape variation on the second stage of labour.
AB  - Fetal head geometry plays an important role in the mechanics of childbirth during
      the second stage labour. Large heads have been shown to be associated with
      difficult and prolonged childbirth. However, the relationship between the fetal
      head geometry and childbirth mechanics has not been quantitatively analysed. To
      address this, our study used finite element (FE) modelling techniques and
      biomechanical simulations to analyse the contribution of fetal head shape and
      size on the mechanics of childbirth. X-ray computed tomography (CT) images from
      26 newborn infants (less than 9 days old) without skull abnormalities were used
      to construct individual-specific FE models of the fetal skull. Simulations of
      childbirth were conducted using each model of the skull and a customised pelvic
      floor model based on magnetic resonance imaging (MRI) of a healthy nulliparous
      woman. The force required for delivery, the maximum principal stresses, and the
      maximum principal stretch ratios at the left and right pelvic floor muscle-pubic
      bone interfaces were quantified. Partial least squares regression (PLSR) models
      for predicting these mechanical indices were constructed using: (i) either the FE
      geometries of the fetal heads or the biometrical parameters (biparietal diameters
      and fetal head circumferences) as inputs; and (ii) either a linear or a quadratic
      function for the inner relation. The predictabilities of the mechanical indices
      using the PLSR models were quantified using a leave-one-out analysis.
      Quantitative associations were found between the geometric parameters of the
      fetal head and the indices of childbirth mechanics. When using the full FE
      geometries as inputs, the PLSR model using a linear inner relation gave better
      predictability than the model using a quadratic inner relation. This could be
      attributed to the quadratic inner relation correlating response to the noise in
      point-to-point correspondence. When using the biometrical parameters of the skull
      as inputs, the PLSR model using a quadratic inner relation gave the best overall
      predictability. Such a model could be implemented in a clinical setting as a
      predictive model for childbirth planning and as an educational tool for clinical
      training.

PMID- 25869692
TI  - The NHS Health Check programme: implementation in east London 2009-2011.
AB  - OBJECTIVES: To describe implementation and results from the National Health
      Service (NHS) Health Check programme. DESIGN: Three-year observational open
      cohort study: 2009-2011. PARTICIPANTS: People of age 40-74 years eligible for an
      NHS Health Check. SETTING: 139/143 general practices in three east London primary
      care trusts (PCTs) serving an ethnically diverse and socially disadvantaged
      population. METHOD: Implementation was supported with education, IT support and
      performance reports. Tower Hamlets PCT additionally used managed practice
      networks and prior-stratification to call people at higher cardiovascular (CVD)
      risk first. MAIN OUTCOMES MEASURES: Attendance, proportion of high-risk
      population on statins and comorbidities identified. RESULTS: Coverage 2009, 2010,
      2011 was 33.9% (31,878/10,805), 60.6% (30,757/18,652) and 73.4% (21,194/28,890),
      respectively. Older people were more likely to attend than younger people.
      Attendance was similar across deprivation quintiles and was in accordance with
      population distributions of black African/Caribbean, South Asian and White ethnic
      groups. 1 in 10 attendees were at high-CVD risk (20% or more 10-year risk). In
      the two PCTs stratifying risk, 14.3% and 9.4% of attendees were at high-CVD risk
      compared to 8.6% in the PCT using an unselected invitation strategy. Statin
      prescription to people at high-CVD risk was higher in Tower Hamlets 48.9%, than
      in City and Hackney 23.1% or Newham 20.2%. In the 6 months following an NHS
      Health Check, 1349 new cases of hypertension, 638 new cases of diabetes and 89
      new cases of chronic kidney disease (CKD) were diagnosed. This represents 1 new
      case of hypertension per 38 Checks, 1 new case of diabetes per 80 Checks and 1
      new case of CKD per 568 Checks. CONCLUSIONS: Implementation of the NHS Health
      Check programme in these localities demonstrates limited success. Coverage and
      treatment of those at high-CVD risk could be improved. Targeting invitations to
      people at high-CVD risk and managed practice networks in Tower Hamlets improved
      performance.

PMID- 25869720
TI  - Numerical analysis of Venous External Scaffolding Technology for Saphenous Vein
      Grafts.
AB  - This paper presents a method for analyzing and comparing numerically Saphenous
      Vein Grafts (SVGs) following Coronary Artery Bypass Graft surgery (CABG). The
      method analyses the flow dynamics inside vein grafts with and without supporting
      using Venous External Scaffolding Technology (VEST). The numerical method uses
      patients' specific computational fluid dynamics (CFD) methods to characterize the
      relevant hemodynamic parameters of patients' SVGs. The method was used to compare
      the hemodynamics of six patient's specific model and flow conditions of stented
      and non-stented SVGs, 12 months post-transplantation. The flow parameters used to
      characterize the grafts' hemodynamics include Time Averaged Wall Shear Stress
      (TAWSS), Oscillatory Shear Index (OSI) and Relative Residence Time (RRT). The
      effect of stenting was clearly demonstrated by the chosen parameters. SVGs under
      constriction of VEST were associated with similar spatial average of TAWSS (10.73
      vs 10.29 dyn/cm(2)), yet had fewer lesions with low TAWSS, lower OSI (0.041 vs
      0.08) and RRT (0.12 vs 0.24), and more uniform flow with less flow discrepancies.
      In conclusion, the suggested method and parameters well demonstrated the
      advantage of VEST support. Stenting vein grafts with VEST improved hemodynamic
      factors which are correlated to graft failure following CABG procedure.

PMID- 25869722
TI  - Defining functional groups based on running kinematics using Self-Organizing Maps
      and Support Vector Machines.
AB  - A functional group is a collection of individuals who react in a similar way to a
      specific intervention/product such as a sport shoe. Matching footwear features to
      a functional group can possibly enhance footwear-related comfort, improve running
      performance, and decrease the risk of movement-related injuries. To match
      footwear features to a functional group, one has to first define the different
      groups using their distinctive movement patterns. Therefore, the main objective
      of this study was to propose and apply a methodological approach to define
      functional groups with different movement patterns using Self-Organizing Maps and
      Support Vector Machines. Further study objectives were to identify differences in
      age, gender and footwear-related comfort preferences between the functional
      groups. Kinematic data and subjective comfort preferences of 88 subjects (16-76
      years; 45 m/43 f) were analysed. Eight functional groups with distinctive
      movement patterns were defined. The findings revealed that most of the groups
      differed in age or gender. Certain functional groups differed in their comfort
      preferences and, therefore, had group-specific footwear requirements to enhance
      footwear-related comfort. Some of the groups, which had group-specific footwear
      requirements, did not show any differences in age or gender. This is important
      because when defining functional groups simply using common grouping criteria
      like age or gender, certain functional groups with group-specific movement
      patterns and footwear requirements might not be detected. This emphasises the
      power of the proposed pattern recognition approach to automatically define groups
      by their distinctive movement patterns in order to be able to address their group
      specific product requirements. 

PMID- 25869721
TI  - Potential role of surface wettability on the long-term stability of dentin bonds
      after surface biomodification.
AB  - Degradation of the adhesive interface contributes to the failure of resin
      composite restorations. The hydrophilicity of the dentin matrix during and after
      bonding procedures may result in an adhesive interface that is more prone to
      degradation over time. This study assessed the effect of chemical modification of
      the dentin matrix on the wettability and the long-term reduced modulus of
      elasticity (Er) of adhesive interfaces. Human molars were divided into groups
      according to the priming solutions: distilled water (control), 6.5%
      Proanthocyanidin-rich grape seed extract (PACs), 5.75% 1-ethyl-3-[3
      dimethylaminopropyl] carbodiimide hydrochloride/1.4% n-hydroxysuccinimide
      (EDC/NHS) and 5% Glutaraldehyde (GA). The water-surface contact angle was
      assessed before and after chemical modification of the dentin matrix. The
      demineralized dentin surface was treated with the priming solutions and restored
      with One Step Plus (OS) and Single Bond Plus (SB) and resin composite. Er of the
      adhesive, hybrid layer and underlying dentin was evaluated after 24h and 30
      months in artificial saliva. The dentin hydrophilicity significantly decreased
      after application of the priming solutions. Aging significantly decreased Er in
      the hybrid layer and underlying dentin of control groups. Er of GA groups
      remained stable over time at the hybrid layer and underlying dentin. Significant
      higher Er was observed for PACs and EDC/NHS groups at the hybrid layer after 24h.
      The decreased hydrophilicity of the modified dentin matrix likely influence the
      immediate mechanical properties of the hybrid layer. Dentin biomodification
      prevented substantial aging at the hybrid layer and underlying dentin after 30
      months storage. 

PMID- 25869723
TI  - Angiotensin-converting enzyme I/D polymorphism and acute respiratory distress
      syndrome.
AB  - BACKGROUND: Some studies have assessed the association between angiotensin
      converting enzyme (ACE) I/D polymorphism and acute respiratory distress syndrome
      (ARDS) risk. However, the results have been inconclusive and contradictory.
      Therefore, we performed a meta-analysis to investigate the association between
      ACE I/D polymorphism and ARDS risk. METHODS: All relevant studies were searched
      using PubMed and EMBASE. Odds ratios (ORs) and corresponding 95% confidence
      intervals (CIs) were estimated using random-effects models or fixed-effects
      models. RESULTS: A total of 14 studies with 5218 subjects were included in this
      meta-analysis. We found that ACE I/D polymorphism significantly associated with
      an increased ARDS risk (OR=1.57; 95% CI 1.30-1.89; P<0.00001). In the subgroup
      analysis by race, Caucasians with ACE I/D polymorphism showed increased ARDS risk
      (OR=1.63; 95% CI 1.32-2.02; P<0.00001). However, Asians with this polymorphism
      did not show significantly increased ARDS risk (OR=1.31; 95% CI 0.90-1.90;
      P=0.95). In the subgroup analysis by age group, adults showed increased ARDS risk
      (OR=1.60; 95% CI 1.32-1.93; P<0.00001), while pediatric patients did not have
      increased ARDS risk (OR=1.15; 95% CI 0.57-2.30; P=0.70). CONCLUSIONS: This meta
      analysis suggested that ACE I/D polymorphism might contribute to the
      susceptibility for ARDS.

PMID- 25869724
TI  - Balance between angiotensin converting enzyme and angiotensin converting enzyme 2
      in patients with chronic heart failure.
AB  - AIM: It has been reported that angiotensin converting enzyme 2 (ACE2) is an
      endogenous counter-regulator of the renin-angiotensin-aldosterone system.
      However, angiotensin converting enzyme (ACE)/ACE2 balance in the development of
      human heart failure is not well established. METHODS: Here we evaluated the
      expression of ACE and ACE2 at the mRNA and protein levels in the myocardium of 78
      patients with mild or moderate to severe heart failure and in 13 cases with
      normal myocardium. RESULTS: In the myocardium of patients with dilated or
      ischemic cardiomyopathy, ACE and ACE2 expression at the mRNA and protein levels
      was significantly increased compared with those in normal myocardium (P<0.01,
      P<0.01, respectively). The ratios of ACE/ACE2 mRNA and ACE/ACE2 were lower in the
      myocardium of patients with mild heart failure than those in normal myocardium
      but higher than those in patients with moderate to severe heart failure.
      CONCLUSIONS: ACE and ACE2 expression at the mRNA and protein levels are
      significantly increased in the myocardium of patients with heart failure. The
      compensatory mechanism of patients with mild heart may cause the decreased
      ACE/ACE2 ratio. However, increased ACE/ACE2 ratios may induce angiotensin II over
      activation and accelerate cardiac remodeling in patients with moderate to severe
      heart failure.

PMID- 25869725
TI  - Additional treatment with 2-Chloro-2-Deoxyadenosine during consolidation in
      children with high-risk acute myeloid leukemia does not improve survival.

PMID- 25869726
TI  - Serum melatonin levels are associated with mortality in severe septic patients.
AB  - OBJECTIVE: Melatonin in septic patients has been scarcely explored and only in
      studies of small sample size (maximum 20 patients). Thus, the objective of this
      study was to determine whether serum melatonin levels are associated with
      severity, oxidant and inflammatory state, and mortality in a large series of
      septic patients. METHODS: A prospective, observational, multicenter study was
      performed in 6 Spanish intensive care units with 201 severe septic patients.
      Serum levels of melatonin were measured at moment of severe sepsis diagnosis. The
      end point was 30-day mortality. RESULTS: Non-surviving patients (n = 71) showed
      higher serum melatonin levels (P < .001) than survivors (n = 130). Multiple
      logistic regression analysis showed that serum melatonin levels were associated
      with 30-day mortality (odds ratio, 1.022; 95% confidence interval, 1.001-1.043; P
      = .04), controlling for serum tumor necrosis factor-alpha levels, serum
      interleukin 6 levels and age. Serum melatonin levels were positively associated
      with serum levels of malondialdehyde as biomarker of oxidative stress,
      interleukin-6 and lactate, and with SOFA score. CONCLUSIONS: The novel finding of
      our study was that serum melatonin levels are associated with mortality in septic
      patients.

PMID- 25869727
TI  - Does participation mediate the prospective relationships of impairment, injury
      severity, and pain to quality of life following burn injury?
AB  - We examined the prospective impact of injury severity, functional impairment, and
      pain on participation in the community and subsequently on life satisfaction and
      self-rated health of 260 burn survivors 5 years post-discharge. Predictor
      variables include injury severity and total body surface area burned (assessed
      during acute care), functional independence (assessed at 12 months post
      discharge), pain (assessed at the 24th month), and participation (assessed at the
      48th month). Participation predicted life satisfaction and self-rated health.
      Functional independence and injury severity had significant indirect influences
      on adjustment via their influence on participation. Pain predicted both outcome
      variables. Clinical and research implications are discussed.

PMID- 25869728
TI  - A retrospective study of judicial encounters of young adults with congenital
      heart disease.
AB  - Young people with congenital heart disease are often marginalised and may
      compensate for restricted physical and social abilities by substance abuse or
      risk-taking behaviour. We report on the judicial encounters of patients in an
      Adult Congenital Heart unit. Fifteen patients had court appearances and all were
      male. Seven served jail sentences, including four indigenous adolescents. All had
      multiple interventions for their cardiac conditions and four are now deceased.
      The majority of patients had mental health issues and substance misuse. These
      patients need psychological and medical support, and help with judicial
      authorities. Recommendations for ongoing care are provided.

PMID- 25869729
TI  - Patients' long-term experiences following obesity surgery with a focus on eating
      behaviour: A qualitative study.
AB  - This study explored long-term consequences of obesity surgery. Interpretative
      phenomenological analysis was used to analyse transcripts of 10 interviews with
      patients who underwent surgery 8 or more years ago. Experiences were described
      under three broad themes: eating behaviours, relationship with food and quality
      of life. Although patients described variability within these themes, describing
      different patterns of change, analysis revealed associations between themes and
      outcomes. In particular, those who reported successful weight loss also described
      the functionalization of food, the development of new coping strategies and a
      process of positive reinvention creating a new sense of self.

PMID- 25869730
TI  - Sensory Hairs in the Bowhead Whale, Balaena mysticetus (Cetacea, Mammalia).
AB  - We studied the histology and morphometrics of the hairs of bowhead whales
      (Balaena mysticetus). These whales are hairless except for two patches of more
      than 300 hairs on the rostral tip of the lower lip and chin, the rostral tip of
      the upper lip, and a bilateral row of approximately ten hairs caudal to the
      blowhole. Histological data indicate that hairs in all three of these areas are
      vibrissae: they show an outermost connective tissue capsule, a circumferential
      blood sinus system surrounding the hair shaft, and dense innervation to the
      follicle. Morphometric data were collected on hair diameters, epidermal recess
      diameters, hair follicle length, and external hair lengths. The main difference
      between the hairs in the different regions is that blowhole hairs have larger
      diameters than the hairs in the chin and rostrum regions. We speculate that the
      hair shaft thickness patterns in bowheads reflect functional specializations.

PMID- 25869731
TI  - The passenger-associated transport repeat promotes virulence factor secretion
      efficiency and delineates a distinct autotransporter subtype.
AB  - Autotransporters are a superfamily of virulence factors secreted by Gram negative
      bacteria. They are comprised of an N-terminal passenger domain that is
      translocated across the outer membrane and a C-terminal domain that inserts into
      the outer membrane forming a beta-barrel anchor. It is still poorly understood
      how the passenger is efficiently translocated in the absence of external energy
      inputs. Several mechanisms have been proposed in solution of this problem, yet
      due to the vast diversity of size, sequence and function of the passenger, it is
      not clear how widely these mechanisms are employed. In this study we functionally
      characterize a conserved repeat found in many passengers that we designate the
      Passenger-associated Transport Repeat (PATR). Using the autotransporter IcsA from
      the enteropathogen Shigella flexneri, we identified conserved PATR residues that
      are required for efficient export of the passenger during growth and infection.
      Furthermore, PATR-containing autotransporters are significantly larger than non
      PATR autotransporters, with PATR copy number correlating with passenger size. We
      also show that PATR-containing autotransporters delineate a subgroup that
      associates with specific virulence traits and architectures. These results
      advance our understanding of autotransporter composition and indicate that an
      additional transport mechanism is important for thousands of these proteins. 

PMID- 25869732
TI  - Pioneers in Pediatric Psychology: Parsimonious Interventions, Serendipity, and
      Collaboration.

PMID- 25869733
TI  - Utilizing cardiac biomarkers to detect and prevent chemotherapy-induced
      cardiomyopathy.
AB  - The success achieved in advances in cancer therapy has been marred by development
      of cardiotoxicity, which causes significant morbidity and mortality. This has led
      to the development of surveillance protocols for cardiotoxicity utilizing
      multimodality imaging techniques and investigation of various drugs to treat and
      prevent cardiotoxicity in this subset of patients. Cardiac biomarkers hold
      important diagnostic and prognostic value in various cardiac diseases. In this
      review, we discuss the use of biomarkers in patients receiving chemotherapy,
      highlighting data behind the use of troponin, B-type natriuretic peptide, and
      myeloperoxidase. We also discuss the use of dexrazoxane, angiotensin-converting
      enzyme inhibitors, and beta blockers in the treatment and prevention of
      chemotherapy-induced cardiotoxicity. Cardiac biomarkers may serve an important
      role in selecting patients that are at high risk of cardiotoxicity and can
      potentially be used to guide the administration of drugs to treat and prevent
      cardiotoxicity. 

PMID- 25869734
TI  - Parental Involvement in Cognitive-Behavioral Intervention for Anxious Children:
      Parents' In-Session and Out-Session Activities and Their Relationship with
      Treatment Outcome.
AB  - The present study explored the role of parents' in-session and out-session
      involvement in CBT for anxious children. Fifty 8- to 12-year-old children with a
      principal DSM-IV anxiety disorder participated in a group CBT program. Parental
      involvement in the therapy was assessed by the clinician and the children and
      parents completed a standardized anxiety scale as the main therapy outcome
      measure, at pre- and post-intervention. In addition, the parents completed
      questionnaires to evaluate a number of possible correlates of parental
      involvement, namely, child's anxiety symptoms intensity and interference,
      parental beliefs about anxiety, expectancies regarding the efficacy of the
      intervention, and parental anxiety. The results indicated that the parents were
      moderately involved in the therapy and that socio-economic status and parental
      beliefs about anxiety were significant correlates of parental involvement.
      Finally, partial support was found for the idea that parents' involvement in the
      therapy might have a positive impact on therapy outcome. 

PMID- 25869735
TI  - Two new phenylpropane glycosides from Allium tuberosum Rottler.
AB  - A phytochemical investigation of Allium tuberosum Rottler afforded two new
      phenylpropane glycosides, named tuberonoid A (1) and B (2), along with four known
      flavonoids, kaempferol 3-O-beta-sophoroside (3), 3-O-beta-D-(2-O-feruloyl)
      glucosyl-7,4'-di-O-beta-D-glucosylkaempferol (4), 3-O-beta-sophorosyl-7-O-beta-D
      (2-O-feruloyl)glucosyl kaempferol (5), kaempferol 3,4'-di-O-beta-D-glucoside (6).
      The identification and structural elucidation of the new compounds were carried
      out based on spectral data analyses ((1)H and (13)C NMR, (1)H-(1)H COSY, HMQC)
      and HR-MS.

PMID- 25869736
TI  - Clinical outcomes of 15 consecutive patients who underwent laparoscopic
      insulinoma resection: The usefulness of monitoring intraoperative blood insulin
      during laparoscopic pancreatectomy.
AB  - BACKGROUND: Insulinoma is a very serious functional tumor. Surgeons should
      confirm complete resection of insulinomas before completing the operation, even
      in laparoscopic surgery. METHODS: Between August 2007 and September 2014, 15
      consecutive patients with biochemical evidence of an insulinoma underwent
      laparoscopic pancreatectomy. Intraoperatively, a peripheral arterial blood sample
      was taken, and insulin was measured by quick insulin assay. Insulin levels were
      determined before anesthesia induction, every 30 min thereafter, and every 30 min
      for at least 1 h after tumor resection to confirm insulin levels did not increase
      before surgery was completed. RESULTS: All 15 patients (3 men and 12 women,
      average age 57.2 years) successfully underwent laparoscopic resection. One
      patient had two tumors, and the remaining 14 patients had one tumor each (three
      in the head, five in the body, and eight in the tail of the pancreas).
      Preoperative localization and regionalization studies identified the tumor
      correctly through CT (12/15 [80.0%]), MRI (9/12 [75.0%]), angiography (11/13
      [84.6%]), endoscopic ultrasonography (7/10 [70.0%]), and selective arterial
      calcium injection (14/14 [100%]). Intraoperative ultrasonography detected 13 of
      15 tumors (86.7%), and intraoperative blood insulin monitoring confirmed the
      complete resection of 16 of 16 tumors (100%). All patients were discharged with
      normal insulin levels and have been followed up for 3-88 months. There has been
      no recurrence of symptoms in any patients and none has died. CONCLUSION: Complete
      removal of an insulinoma can be reliably predicted by intraoperative blood
      insulin monitoring even in laparoscopic pancreatectomies.

PMID- 25869737
TI  - Detection of precancerous gastric lesions and gastric cancer through exhaled
      breath.
AB  - OBJECTIVES: Timely detection of gastric cancer (GC) and the related precancerous
      lesions could provide a tool for decreasing both cancer mortality and incidence.
      DESIGN: 968 breath samples were collected from 484 patients (including 99 with
      GC) for two different analyses. The first sample was analysed by gas
      chromatography linked to mass spectrometry (GCMS) while applying t test with
      multiple corrections (p value<0.017); the second by cross-reactive nanoarrays
      combined with pattern recognition. For the latter, 70% of the samples were
      randomly selected and used in the training set while the remaining 30%
      constituted the validation set. The operative link on gastric intestinal
      metaplasia (OLGIM) assessment staging system was used to stratify the
      presence/absence and risk level of precancerous lesions. Patients with OLGIM
      stages III-IV were considered to be at high risk. RESULTS: According to the GCMS
      results, patients with cancer as well as those at high risk had distinctive
      breath-print compositions. Eight significant volatile organic compounds (p
      value<0.017) were detected in exhaled breath in the different comparisons. The
      nanoarray analysis made it possible to discriminate between the patients with GC
      and the control group (OLGIM 0-IV) with 73% sensitivity, 98% specificity and 92%
      accuracy. The classification sensitivity, specificity, and accuracy between the
      subgroups was as follows: GC versus OLGIM 0-II-97%, 84% and 87%; GC versus OLGIM
      III-IV-93%, 80% and 90%; but OLGIM I-II versus OLGIM III-IV and dysplasia
      combined-83%, 60% and 61%, respectively. CONCLUSIONS: Nanoarray analysis could
      provide the missing non-invasive screening tool for GC and related precancerous
      lesions as well as for surveillance of the latter. TRIAL REGISTRATION NUMBER:
      Clinical Trials.gov number, NCT01420588 (3/11/2013).

PMID- 25869738
TI  - Stroke mimicking relapse in a patient with CLIPPERS syndrome.

PMID- 25869739
TI  - Combined effects of motor response, sensory modality, and stimulus intensity on
      temporal reproduction.
AB  - The ability to estimate a filled interval of time is affected by numerous non
      temporal factors, such as the sensory modality, duration, and the intensity of
      the stimulus. Here we explore the role of modality (auditory or visual), stimulus
      intensity (low vs. high), and motor response speed on the ability to reproduce
      the duration of short (<1 s) filled intervals. In accordance with the literature,
      the reproduced duration was affected by both the modality and the intensity of
      the stimulus; longer reproduction times were generally observed for visual as
      compared to auditory stimuli, and for low as compared to high-intensity stimuli.
      We used general estimating equations in order to determine whether these factors
      independently affected participants' ability to reproduce a given duration, after
      eliminating the variability associated with reaction time, since it covaried with
      the reproduced durations. This analysis revealed that stimulus duration,
      modality, and intensity were all significant independent predictors of the
      reproduced durations. Additionally, duration interacted with intensity when
      reproducing auditory intervals. That is, after taking into account the general
      speeding-up effect that high-intensity stimuli have on responses, they seem to
      have an additional effect on the rate of the internal clock. These results
      support previous evidence suggesting that auditory and visual clocks run at
      different speeds.

PMID- 25869740
TI  - The effect of apolipoprotein E4 on synchronous neural interactions in brain
      cultures.
AB  - In a previous study, we assessed the synchronous neural interactions (SNI) in a
      developing neural network in brain cultures on multielectrode arrays
      (Christopoulos et al. in J Neural Eng 9:046008, 2012). Here, we report on the
      effects of apolipoprotein E4 (apoE4) on these neural interactions. We carried out
      six experiments (five using rodent brain cultures and one using neuroblastoma
      cultures) in which we recorded local field potentials (LFP) from 59 sites for
      several days in vitro under the following conditions. In one experiment, we added
      to the culture media triglyceride (TG)-rich lipoproteins from a human subject
      with the apoE4/4 genotype, whereas in the other experiments, we added recombinant
      human apoE4. We found that SNI in the apoE4-treated cultures had higher
      coefficient of SNI variation, as compared to control cultures. These findings
      further document the role of SNI as a fundamental aspect of the dynamic
      organization of neural networks (Langheim et al. in Proc Natl Acad Sci USA
      103:455-459, 2006. doi: 10.1073/pnas.0509623102 ; Georgopoulos et al. in J Neural
      Eng 4:349-355, 2007) and extend the effect of apoE4 on SNI (Leuthold et al. in
      Exp Brain Res 226:525-536, 2013) across different brain species (human, rodents),
      apoE source (TG-rich lipoproteins, recombinant), neural signals (MEG, LFP), and
      brain network (intact brain, developing brain in vitro). To our knowledge, this
      is the first study of the effects of apoE4 on neural network function in vitro.

PMID- 25869741
TI  - Pantomime-grasping: the 'return' of haptic feedback supports the absolute
      specification of object size.
AB  - When an individual grasps a physical object, the visuomotor system is able to
      specify grip aperture via absolute visual information. In contrast, grasping to a
      location previously occupied by an object (i.e., pantomime-grasping) results in
      the specification of grip aperture via relative visual information. The basis for
      the dissociable visual codes is thought to reflect that pantomime-grasping is a
      perception-based task. It is, however, important to recognize that grasping a
      physical object and pantomime-grasping differ not only in terms of their
      visuospatial properties but also with respect to the availability of haptic
      feedback: Grasping a physical object provides haptic cues derived from touching
      the object, whereas no such feedback is available in a traditional pantomime
      grasping task. As such, we examined whether haptic feedback influences the
      information supporting a pantomime-grasp performed after a 1000-ms visual delay.
      Participants completed responses in each of the three tasks: (1) grasping a
      physical object, (2) traditional pantomime-grasping wherein the to-be-grasped
      object was removed from the grasping environment and (3) pantomime-grasping
      wherein the experimenter placed the object between participants' thumb and
      forefinger once they had completed their response (i.e., pantomime-grasping with
      haptic feedback). Just-noticeable-difference (JND) scores were computed to
      determine whether responses adhered to or violated the psychophysical (i.e.,
      relative) principles of Weber's law. JNDs for the traditional pantomime-grasping
      task adhered to Weber's law, whereas JNDs for grasping a physical object and for
      pantomime-grasping with haptic feedback violated the law. Thus, we propose that
      convergent visual and haptic cues support the absolute specification of object
      size in a pantomime-grasping task. Furthermore, our results highlight the
      important role of multisensory cue integration in a target-defined grasping task.

PMID- 25869742
TI  - Coordination of digit force variability during dominant and non-dominant
      sustained precision pinch.
AB  - This study examined the effects of handedness on the inter-digit coordination of
      force variability with and without concurrent visual feedback during sustained
      precision pinch. Twenty-four right-handed subjects were instructed to pinch an
      instrumented apparatus with their dominant and non-dominant hands, separately.
      During the pinch, the subjects were required to maintain a stable force output at
      5 N for 1 min. Visual feedback was given for the first 30 s and removed for the
      second 30 s. Coefficient of variation and detrended fluctuation analysis were
      employed to examine the amount and structural variability of the thumb and index
      finger forces. Similarly, correlation coefficient and detrended cross-correlation
      analysis were applied to quantify the inter-digit correlation of force amount and
      structural variability. Results showed that, compared to the non-dominant hand,
      the dominant hand had higher inter-digit difference in the amount of digit force
      variability. Without visual feedback, the dominant hand exhibited lower digit
      force structural variability but higher inter-digit force structural correlation
      than the non-dominant hand. These results implied that the dominant hand would be
      more independent, less flexible and with lower dynamic degrees of freedom than
      the non-dominant hand in coordination of the thumb and index finger forces during
      sustained precision pinch. The effects of handedness on inter-digit force
      coordination were dependent on sensory condition, which shed light on higher
      level sensorimotor mechanisms that may be responsible for the asymmetries in
      coordination of digit force variability. 

PMID- 25869745
TI  - Establishment of Genetic Transformation in the Sexually Reproducing Diatoms
      Pseudo-nitzschia multistriata and Pseudo-nitzschia arenysensis and Inheritance of
      the Transgene.
AB  - We report the genetic transformation of the planktonic diatoms Pseudo-nitzschia
      arenysensis and Pseudo-nitzschia multistriata, members of the widely distributed
      and ecologically important genus Pseudo-nitzschia. P. arenysensis and P.
      multistriata present the classical size reduction/restitution life cycle and can
      reproduce sexually. Genetic transformation was achieved with the biolistic
      method, using the H4 gene promoter from P. multistriata to drive expression of
      exogenous genes. The transformation was first optimized introducing the Sh ble
      gene to confer resistance to the antibiotic zeocin. Integration of the transgene
      was confirmed by PCR and Southern blot analyses. Subsequently, we simultaneously
      transformed in P. arenysensis two plasmids, one encoding the beta-glucuronidase
      (GUS) gene together with the plasmid carrying the Sh ble resistance gene,
      demonstrating the possibility of co-transformation. By transforming a gene
      encoding a fusion between the histone H4 and the green fluorescent protein (GFP),
      we demonstrated that fluorescent tagging is possible and that studies for protein
      localization are feasible. Importantly, we crossed P. arenysensis- and P.
      multistriata-transformed strains with a wild-type strain of opposite mating type
      and demonstrated that the transgene can be inherited in the F1 generation. The
      possibility to transform two diatom species for which genetic crosses are
      possible opens the way to a number of new approaches, including classical loss of
      function screens and the possibility to obtain different combinations of double
      transformants. 

PMID- 25869743
TI  - Treatment of Eczema: Corticosteroids and Beyond.
AB  - Atopic dermatitis (AD) is a chronic inflammatory skin condition that requires a
      manifold approach to therapy. The goal of therapy is to restore the function of
      the epidermal barrier and to reduce skin inflammation. This can be achieved with
      skin moisturization and topical anti-inflammatory agents, such as topical
      corticosteroids and calcineurin inhibitors. Furthermore, proactive therapy with
      twice weekly use of both topical corticosteroids and calcineurin inhibitors in
      previously affected areas has been found to reduce the time to the next
      eczematous flare. Adjunctive treatment options include wet wrap therapy, anti
      histamines, and vitamin D supplementation. Bacterial colonization, in particular
      Staphylococcus aureus, can contribute to eczematous flares and overt infection.
      Use of systemic antibiotics in infected lesions is warranted; however, empiric
      antibiotics use in uninfected lesions is controversial. Local antiseptic measures
      (i.e., bleach baths) and topical antimicrobial therapies can be considered in
      patients with high bacterial colonization. Difficult-to-treat AD is a complex
      clinical problem that may require re-evaluation of the initial diagnosis of AD,
      especially if the onset of disease occurs in adulthood. It may also necessitate
      evaluation for contact, food, and inhaled allergens that may exacerbate the
      underlying AD. There are a host of systemic therapies that have been successful
      in patients with difficult-to-treat AD, however, these agents are limited by
      their side effect profiles. Lastly, with further insight into the pathophysiology
      of AD, new biological agents have been investigated with promising results.

PMID- 25869746
TI  - Can 3'-Deoxy-3'-((18)F) Fluorothymidine Out Perform 2-Deoxy-2-((18)F) Fluoro-D
      Glucose Positron Emission Tomography/Computed Tomography in the Diagnosis of
      Cervical Lymphadenopathy in Patients With Oral/Head and Neck Cancer?
AB  - PURPOSE: The present study investigated the performance of cellular metabolism
      imaging with 2-deoxy-2-((18)F) fluoro-D-glucose (FDG) versus cellular
      proliferation imaging with 3'-deoxy-3'-((18)F) fluorothymidine (FLT) in the
      detection of cervical lymph node metastases in oral/head and neck cancer.
      MATERIALS AND METHODS: We conducted a prospective cohort study to assess a head
      to-head performance of FLT imaging and clinical FDG imaging for characterizing
      cervical lymph node metastases in patients with squamous cell carcinoma (SCC) of
      the oral/head and neck region. The primary predictor variable of the study was
      the presence of FDG or FLT avidity within the cervical lymph nodes. The primary
      outcome variable was the histologic presence of metastatic SCC in the cervical
      lymph nodes. The performance was reported in terms of the sensitivity,
      specificity, accuracy, and positive and negative predictive values. The overall
      accuracy for discriminating positive from negative lymph nodes was evaluated as a
      function of the positron emission tomography (PET) standardized uptake value
      (SUV). Receiver operating characteristic (ROC) analyses were performed for both
      tracers. RESULTS: Eleven patients undergoing surgical resection of SCC of the
      oral/head and neck region underwent preoperative FDG and FLT PET-computed
      tomography (CT) scans on separate days. The interpretation of the FDG PET-CT
      imaging resulted in sensitivity, specificity, accuracy, positive predictive
      value, and negative predictive value of 43.2, 99.5, 94.4, 88.9, and 94.7%,
      respectively. The sensitivity, specificity, accuracy, positive predictive value,
      and negative predictive value for FLT PET-CT imaging was 75.7, 99.2, 97.1, 90.3,
      and 97.7%, respectively. The areas under the curve for the ROC curves were 0.9
      and 0.84 for FDG and FLT, respectively. Poor correlation was observed between the
      SUV for FDG and FLT within the lymph nodes and tumors. CONCLUSION: FLT showed
      better overall performance for detecting lymphadenopathy on qualitative
      assessment within the total nodal population. This notwithstanding, FDG SUV
      performed better for pathologic discrimination within the visible lymph nodes.

PMID- 25869747
TI  - Hemi-Bernard method: straightforward reconstruction of lower lip after malignant
      tumor resection.
AB  - The Bernard method is a straightforward method for reconstructing lower lip
      defects after tumor resection. However, this method is difficult to apply when
      the defect is located on the unilateral side of the lower lip. This report
      describes the reconstruction of unilateral lower lip defects using a modified
      Bernard method, which is referred to as the hemi-Bernard method. Three patients
      (2 male and 1 female; mean defect, 55%) underwent reconstruction using the hemi
      Bernard method after lower lip malignant tumor resection. No infection or flap
      necrosis occurred, and none of the 3 patients had difficulty with oral ingestion.
      Movement of the orbicularis oris muscle was retained in all patients. The hemi
      Bernard method is straightforward and has several advantages, including extension
      of lower lip length. This method could be useful for reconstructing full
      thickness defects located on the unilateral side of the lower lip. 

PMID- 25869748
TI  - Clinicopathological Characteristics and Outcome Predictors in Squamous Cell
      Carcinoma of the Maxillary Gingiva and Hard Palate.
AB  - PURPOSE: Squamous cell carcinoma (SCC) located in the maxillary gingiva and hard
      palate is relatively rare. There are few published guidelines for the treatment
      of SCC of the maxilla. The aim of the present study was to characterize the
      clinicopathologic features of SCC of the maxillary gingiva and hard palate and
      determine factors that predict outcome and lead to a strategic treatment plan.
      MATERIALS AND METHODS: A retrospective cohort study of patients with SCC of the
      maxillary gingiva and hard palate was conducted from 2003 to 2012 at the
      Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology,
      Nanjing Medical University. Clinicopathologic characteristics, treatments,
      outcome predictors, and 3- and 5-year overall survival rates were analyzed. The
      Kaplan-Meier method was used to evaluate 3- and 5-year overall survival rates.
      Univariate and multivariate Cox regression analyses were used to identify
      predictors of survival. A P value less than .05 was considered statistically
      significant. RESULTS: The 3- and 5-year survival rates of the 62 participants
      were 66.6 and 57.3%, respectively. Univariate analyses showed statistically
      significant (P < .05) associations between patient survival rate and tumor
      differentiation grade, T classification, marginal status, cervical lymphatics,
      and local recurrence. Occult lymph node metastases of maxillary SCC in tumor
      stages T2 to T4 occurred in 20 to 40% of patients. Patients who presented with
      lesions located after the first premolar plane area and received postoperative
      radiotherapy had a better prognosis. CONCLUSION: Elective neck dissection is
      recommended for management of T2 to T4 SCCs in the maxillary gingiva and hard
      palate. Postoperative radiotherapy can improve the prognosis and decrease the
      recurrence of SCC after the first premolar plane area.

PMID- 25869750
TI  - Improved low-CPA vitrification of mouse oocytes using quartz microcapillary.
AB  - Cryopreservation by low-cryoprotectant (CPA) vitrification has the potential to
      combine all the advantages of the conventional high-CPA vitrification and slow
      freezing approaches while avoiding their drawbacks. However, current low-CPA
      vitrification protocol for cryopreservation of oocytes requires a lengthy and
      multi-step procedure for unloading CPAs. In this study, we report a much
      simplified procedure of using quartz microcapillary (QMC) for low-CPA
      vitrification of mouse oocytes with only one step for unloading CPAs. The
      immediate viability of oocytes after the improved low-CPA vitrification was
      determined to be more than 90%. Moreover, no significant difference was observed
      in terms of embryonic development from the two-cell to blastocyst stages between
      the fresh and vitrified oocytes after in vitro fertilization (IVF). This improved
      low-CPA vitrification technology has the potential for efficient cryopreservation
      of oocytes to preserve the fertility of mammals including humans for assisted
      reproductive medicine, maintenance of animal resource and endangered species, and
      livestock management. 

PMID- 25869751
TI  - A pilot study on nicotine residues in houses of electronic cigarette users,
      tobacco smokers, and non-users of nicotine-containing products.
AB  - BACKGROUND: Nicotine deposited on the surfaces has been shown to react with
      airborne chemicals leading to formation of carcinogens and contributing to
      thirdhand exposure. While prior studies revealed nicotine residues in tobacco
      smokers' homes, none have examined the nicotine residue in electronic cigarette
      (e-cigarette) users' homes. METHODS: We measured nicotine on the surfaces in
      households of 8 e-cigarette users, 6 cigarette smokers, and 8 non-users of
      nicotine-containing products in Western New York, USA. Three surface wipe samples
      were taken from the floor, wall and window. Nicotine was extracted from the wipes
      and analyzed using gas chromatography. RESULTS: Half of the e-cigarette users'
      homes had detectable levels of nicotine on surfaces whereas nicotine was found in
      all of the tobacco cigarette smokers' homes. Trace amounts of nicotine were also
      detected in half of the homes of non-users of nicotine-containing products.
      Nicotine levels in e-cigarette users homes was significantly lower than that
      found in cigarette smokers homes (average concentration 7.7+/-17.2 vs. 1303+/
      2676 MUg/m2; p<0.05). There was no significant difference in the amount of
      nicotine in homes of e-cigarette users and non-users (p>0.05). CONCLUSIONS:
      Nicotine is a common contaminant found on indoor surfaces. Using e-cigarettes
      indoors leads to significantly less thirdhand exposure to nicotine compared to
      smoking tobacco cigarettes.

PMID- 25869752
TI  - When meningioma becomes an emergency: Nocardial brain abscesses superimposed on
      meningioma.

PMID- 25869753
TI  - New-generation atrial antitachycardia pacing (Reactive ATP) is associated with
      reduced risk of persistent or permanent atrial fibrillation in patients with
      bradycardia: Results from the MINERVA randomized multicenter international trial.
AB  - BACKGROUND: Atrial fibrillation (AF) is a frequent comorbidity in patients with
      pacemaker and is a recognized cause of mortality, morbidity, and quality-of-life
      impairment. The international MINimizE Right Ventricular pacing to prevent Atrial
      fibrillation and heart failure trial established that atrial preventive pacing
      and atrial antitachycardia pacing (DDDRP) in combination with managed ventricular
      pacing (MVP) reduce permanent AF occurrence in comparison with standard dual
      chamber pacing (DDDR). OBJECTIVE: We aimed to determine the role of new
      generation atrial antitachycardia pacing (Reactive ATP) in preventing AF disease
      progression. METHODS: Patients with dual-chamber pacemaker and with previous
      atrial tachyarrhythmias were randomly assigned to DDDR (n = 385 (33%)), MVP (n =
      398 (34%)), or DDDRP+MVP (n = 383 (33%)) group. The incidence of permanent AF, as
      defined by the study investigator, or persistent AF, defined as >=7 consecutive
      days with AF, was estimated using the Kaplan-Meier method, while its association
      with patients' characteristics was evaluated via multivariable Cox regression.
      RESULTS: At 2 years, the incidence of permanent or persistent AF was 26% (95%
      confidence interval [CI] 22%-31%) in the DDDR group, 25% (95% CI 21%-30%) in the
      MVP group, and 15% (95% CI 12%-20%) in the DDDRP+MVP group (P < .001 vs. DDDR; P
      = .002 vs. MVP). Generalized estimating equation-adjusted Reactive ATP efficacy
      was 44.4% (95% CI 41.3%-47.6%). Multivariate modeling identified high Reactive
      ATP efficacy (>44.4%) as a significant predictor of reduced permanent or
      persistent AF risk (hazard ratio 0.32; 95% CI 0.13-0.781; P = .012) and episodes'
      characteristics, such as long atrial arrhythmia cycle length, regularity, and the
      number of rhythm transitions, as predictors of high ATP efficacy. CONCLUSION: In
      patients with bradycardia, DDDRP+MVP delays AF disease progression, with Reactive
      ATP efficacy being an independent predictor of permanent or persistent AF
      reduction.

PMID- 25869755
TI  - Pretreatment with curcumin attenuates anxiety while strengthens memory
      performance after one short stress experience in male rats.
AB  - It is observed that memories are more strengthened in a stressful condition.
      Studies have also demonstrated an association between stressful events and the
      onset of depression and anxiety. Considering the nootropic, anxiolytic and
      antidepressant-like properties of curcumin in various experimental approaches, we
      appraised the beneficial effects of this herb on acute immobilization stress
      induced behavioral and neurochemical alterations. Rats in test group were
      administrated with curcumin (200mg/kg/day), dissolved in neutral oil, for 1 week.
      Both control and curcumin-treated rats were divided into unstressed and stressed
      groups. Rats in the stressed group were subjected to immobilization stress for
      2h. After stress, the animals were subjected to behavioral tests. Immobilization
      stress induced an anxiogenic behavior in rats subjected to elevated plus maze
      test (EPM). Locomotor activity was also significantly increased following the
      acute immobilization stress. Pre-administration of curcumin prevented the stress
      induced behavioral deficits. Highest memory performance was observed in stressed
      rats that were pre-treated with curcumin in Morris water maze (MWM). Brain
      malondialdehyde (MDA) levels, catalase (CAT), glutathione peroxidase (GPx),
      superoxide dismutase (SOD), and acetylcholinesterase (AChE) activities were also
      estimated. Present study suggests a role of antioxidant enzymes in the
      attenuation of acute stress induced anxiety by curcumin. The findings therefore
      suggest that supplementation of curcumin may be beneficial in the treatment of
      acute stress induced anxiety and enhancement of memory function. 

PMID- 25869756
TI  - Risk factors for recurrent colonization with methicillin-resistant Staphylococcus
      aureus in community-dwelling adults and children.
AB  - OBJECTIVE To identify risk factors for recurrent methicillin-resistant
      Staphylococcus aureus (MRSA) colonization. DESIGN Prospective cohort study
      conducted from January 1, 2010, through December 31, 2012. SETTING Five adult and
      pediatric academic medical centers. PARTICIPANTS Subjects (ie, index cases) who
      presented with acute community-onset MRSA skin and soft-tissue infection. METHODS
      Index cases and all household members performed self-sampling for MRSA
      colonization every 2 weeks for 6 months. Clearance of colonization was defined as
      2 consecutive sampling periods with negative surveillance cultures. Recurrent
      colonization was defined as any positive MRSA surveillance culture after
      clearance. Index cases with recurrent MRSA colonization were compared with those
      without recurrence on the basis of antibiotic exposure, household demographic
      characteristics, and presence of MRSA colonization in household members. RESULTS
      The study cohort comprised 195 index cases; recurrent MRSA colonization occurred
      in 85 (43.6%). Median time to recurrence was 53 days (interquartile range, 36-84
      days). Treatment with clindamycin was associated with lower risk of recurrence
      (odds ratio, 0.52; 95% CI, 0.29-0.93). Higher percentage of household members
      younger than 18 was associated with increased risk of recurrence (odds ratio,
      1.01; 95% CI, 1.00-1.02). The association between MRSA colonization in household
      members and recurrent colonization in index cases did not reach statistical
      significance in primary analyses. CONCLUSION A large proportion of patients
      initially presenting with MRSA skin and soft-tissue infection will have recurrent
      colonization after clearance. The reduced rate of recurrent colonization
      associated with clindamycin may indicate a unique role for this antibiotic in the
      treatment of such infection.

PMID- 25869754
TI  - J-wave syndromes: Brugada and early repolarization syndromes.
AB  - A prominent J wave is encountered in a number of life-threatening cardiac
      arrhythmia syndromes, including the Brugada syndrome and early repolarization
      syndromes. Brugada syndrome and early repolarization syndromes differ with
      respect to the magnitude and lead location of abnormal J waves and are thought to
      represent a continuous spectrum of phenotypic expression termed J-wave syndromes.
      Despite two decades of intensive research, risk stratification and the approach
      to therapy of these 2 inherited cardiac arrhythmia syndromes are still undergoing
      rapid evolution. Our objective in this review is to provide an integrated
      synopsis of the clinical characteristics, risk stratifiers, and molecular, ionic,
      cellular, and genetic mechanisms underlying these 2 fascinating syndromes that
      have captured the interest and attention of the cardiology community in recent
      years. 

PMID- 25869757
TI  - Influence of various factors on functional dyspepsia.
AB  - Aim of the research is to establish the prevalence of dyspepsia in Osjecko
      baranjska County, to establish its specific characteristics and to determine the
      effect of demographic, anthropometric, and socioeconomic factors. It is a cross
      sectional and case control study conducted in 2010 on systematic sample of 900
      subjects between 20 and 69 years of age. Every subject was sent an invitation
      letter and a Rome III diagnostic questionnaire for one of the disorders. A
      scoring algorithm was used to confirm or exclude the diagnosis of functional
      dyspepsia (FD). The chi-square test, t-test and logistic regression were used for
      analysis.Prevalence of dyspepsia was recorded in 16, 56%, of subjects. There is
      no statistically significant difference in prevalence of dyspepsia male and
      female. The prevalence of dyspepsia increases with age. Correlation with the
      place of birth was proven. There is no correlation between the current place of
      residence (rural area and town) and dyspepsia. There is a correlation with
      marital status. Correlation between stool forms was proven. There were a greater
      number of subjects that had at least one alarm symptom or some of the
      psychosocial factors and they often suffered from a chronic disease. The risk for
      dyspepsia increases with age, body mass index (BMI), and poorer health. Logistic
      regression showed the following as statistically significant for dyspepsia: place
      of birth and self-assessment of one's health. FD presents a significant health
      problem. Rome III survey questionnaire proved to be an acceptable method for
      diagnosing this functional disorder in clinical-consilliary and primary health
      care for persons showing signs of alarm and needing further diagnostic treatment.

PMID- 25869758
TI  - Can circulating M30 and M65 levels be beneficial markers in the diagnosis and
      management of patients with complete hydatidiform mole?
AB  - OBJECTIVE: The objective of this study is to evaluate the prognostic value of M30
      and M65 levels as markers of apoptotic activity and maternal serum oxidative
      stress in patients with complete hydatidiform mole (CHM). METHODS: In total, 68
      pregnant women were included in the study. The study group included 34 pregnant
      with CHM, while 34 healthy pregnant were employed as a control group. Venous
      blood samples were drawn to assess the maternal serum oxidative stress and M30
      M65 levels. In addition, a second blood sample was drawn from patients with CHM
      on day 8 after dilatation evacuation. RESULTS: Maternal serum oxidative stress
      and M30-M65 levels were found to be significantly higher in patients with CHM as
      compared with the control group. It was found that serum beta-subunit of human
      chorionic gonadotropin (beta-hCG) level had a significant positive correlation
      with M30-M65 levels in patients with CHM. In addition, serum M65 level was found
      to be as effective as beta-hCG in the identification of the patients with CHM.
      CONCLUSION: Our results indicated that oxidative stress and apoptosis may play
      significant roles in CHM development. In addition, it seems that serum M30-M65
      levels can presumably be an ancillary laboratory test to beta-hCG in the
      diagnosis and follow-up of the patients with CHM.

PMID- 25869759
TI  - Nonalcoholic fatty liver may increase the risk of operation in patients with
      fatty liver and the frequency of cancer in their first-degree relatives.
AB  - BACKGROUND: Fatty liver is a common disease in developed countries. We
      investigated the frequency of operation in patients with fatty liver and the
      frequency of cancer in their first-degree relatives. METHODS: In this study, we
      evaluated 105 patients with biopsy-proven nonalcoholic fatty liver disease
      (NAFLD), 121 patients with hepatitis C (61 patients with fatty liver and 60
      patients without fatty liver), 50 patients with inflammatory bowel disease (IBD),
      and 109 patients with dyspepsia as a control group. RESULTS: There was no
      difference for sex, mean age, and marital status among the groups, except that
      patients with IBD were younger than others (p < 0.001). The frequency of cancer
      in family was as follows: 18 % in IBD, 9 % in dyspepsia, 28 % in hepatitis C with
      hepatic steatosis, 21.5 % in hepatitis C without steatosis, and 27 % in NAFLD (p
      = 0.006). Then, we divided the study group into two groups-group 1: IBD +
      dyspepsia + hepatitis C without hepatic steatosis, and group 2: hepatitis C with
      hepatic steatosis + NAFLD-and performed the same analysis. We found that the
      frequency of cancer in family was 16 % in group 1 (the patients without fatty
      liver) vs. 24.4 % in group 2 (those with fatty liver; p = 0.037). We also
      investigated the rate of operation in patients. The results were as follows: 33 %
      in group 1 vs. 43 % in group 2 (p = 0.043). CONCLUSIONS: Independently of the
      underlying chronic diseases, occurrence of fat in the liver increased the
      frequency of operation in patients with fatty liver and the rate of cancer in
      their first-degree relatives. Understanding the underlying causes of fatty liver
      forms might decrease the cancer frequency in the population and number of
      operation in patients with fatty liver.

PMID- 25869760
TI  - The seroprevalence of both hepatitis B and hepatitis C at the first-step health
      organizations and the difference between the urban and rural areas.
AB  - BACKGROUND: Hepatitis B virus (HBV) and hepatitis C virus (HCV) are very
      important infectious agents for public health. The aim of this retrospective
      study was to assess the seroprevalence of hepatitis B surface antigen (HBsAg),
      hepatitis B surface antibody (anti-HBs) and anti-HCV test results of patients who
      admitted to first-step health organizations in central and peripheral districts
      of Konya, the central region of Turkey during the period 2005-2010. METHODS: In
      this study, HBsAg, anti-HBs and anti-HCV screening test results of patients who
      admitted to first-step health organizations in Konya during the period 2005-2010
      were retrospectively investigated from the laboratory records. This study was
      approved by the Konya Health Directorate. All screening tests were performed on
      the automatic third-generation enzyme-linked immunosorbent assay (MEIA). This
      immunoassay method was carried out according to the instructions of the
      manufacturer. Borderline and positive results were retested. RESULTS: Konya is
      the largest city of Turkey in terms of surface area and one of the economically
      developed cities. For HBsAg, anti-HBs and anti-HCV screening, whole test results
      of 5 years are given in Table 1 and Figure 1. The differences between the urban
      and rural for HBsAg (p = 0.062 > 0.05) and anti-HCV(p = 0.874 > 0.05) were not
      statistically significant. Among the markers only for anti-HBs, the difference
      between the urban and rural was statistically significant (P = 0.042 < 0.05). Of
      them, 4.15 % were positive for HBsAg, 36.46 % were positive for anti-HBs and 1.16
      % were positive for anti-HCV. CONCLUSION: In this study, Konya has been evaluated
      as two regions: central and peripheral. Our study showed us that distribution of
      the diseases vary from one region to another. We consider that difference in
      social diversity is one of the factors. These infections are major health
      problems. So the results of immunodiagnostic tests for HBsAg, anti-HBs and anti
      HCV will be useful for guiding control actions and for new preventive strategies.

PMID- 25869761
TI  - Can platelet indices be used as predictors of complication in subjects with
      appendicitis?
AB  - BACKGROUND: We examined the changes of mean platelet volume (MPV) and platelet
      distribution width (PDW) in subjects with appendicitis and whether MPV and PDW
      could be used to predict the development of complication due to appendicitis.
      METHODS: The healthy control group, the cases of appendicitis with perforation,
      and the cases of appendicitis without perforation were compared with regard to
      MPV and PDW. We determined whether MPV and PDW were independent variables
      predictive of the development of complication in subjects with appendicitis.
      RESULTS: This retrospective case-control study included a total of 362 patients
      (249 of which were male (68.8 %) and 113 were female (31.2 %); median age, 30
      [range, 18-84 years]). One hundred and ninety-two subjects (53 %) presented with
      appendicitis and 170 (47 %) comprised the healthy control group. Sixty-six (18.2
      %) of the subjects with appendicitis developed complication. MPVs were lower in
      subjects of appendicitis without complication compared to the subjects of
      appendicitis with complication and the control group (MPV, 9.78 +/- 0.99 vs.
      10.20 +/- 1.21 and 10.14 +/- 1.03, respectively [p = 0.005]). The PDW levels were
      not different between the three groups. Independent variables predictive of the
      presence of complication included increased MPV and time from onset of symptoms
      to hospital presentation (odds ratio[confidence interval], p-value: 1.507[1.064
      2.133], 0.021 and 18.887[5.139-69.410], 0.0001, respectively). CONCLUSIONS: Our
      findings suggested these, MPV values in cases of appendicitis without
      complication were lower than the cases with complication and healthy control and
      MPV is a predictor of the development of complication in subjects with
      appendicitis.

PMID- 25869762
TI  - Ectopic acromegaly due to a growth hormone-secreting neuroendocrine
      differentiated tumor developed from ovarian mature cystic teratoma.
AB  - Acromegaly is a clinical syndrome caused by the overproduction of growth hormone
      (GH) and also known as a rare disease. Clinical, biochemical, and radiological
      features are often indistinguishable between GH-producing hypophysis adenomas and
      ectopic GH-releasing hormone (GHRH)-producing tumors. A 40-year-old woman
      presented to us with her growing feet, hands especially fingers, and enlarging
      nose. Biochemical diagnosis of acromegaly was made by measuring insulin-like
      growth factor-1 (IGF-1) level and glucose-suppressed GH estimation. Her spot IGF
      1 level was 1300 ng/ml (90-226 ng/ml). The basal GH was 30 ng/l, and 60- and 120
      min GH levels after 75-g oral glucose load were 29 and 40 ng/l, respectively.
      Magnetic resonance imaging (MRI) of pituitary was normal. There was no pituitary
      adenoma or pituitary hyperplasia. Extrapituitary ectopic hypersecretion of GH or
      GHRH-secreting tumor search was done by high-resolution computed tomography (CT)
      of chest and whole abdomen. Abdomen CT revealed 9.5 * 8 cm pelvic mass, which
      included calcific regions and solid component. The specimen's immunohistochemical
      staining with GH was positive but interestingly GHRH was negative. According to
      immunohistochemical staining, the patient's diagnosis was ectopic acromegaly due
      to a GH-secreting neuroendocrine-differentiated tumor developed from an ovarian
      mature cystic teratoma. Herein, we present excellent illustration of an unusual
      and confusing clinical scenario of ectopic acromegaly.

PMID- 25869763
TI  - Quasi-2d fluids of dipolar superballs in an external field.
AB  - The structure of quasi-2d solutions of dipolar superballs in the fluid state has
      been determined by Metropolis Monte Carlos simulations in the absence and the
      presence of an external field. Superballs are 3d objects characterized by a one
      shape parameter. Here, superballs resembling cubes, but possessing rounded edges,
      have been used. Examination has been made for several magnitudes of the dipole
      moment in three different dipole directions. In the limit of a cube, the
      directions become (i) the center of mass - the center of a face (001) direction,
      (ii) the center of mass - the center of an edge (011) direction, and (iii) the
      center of mass - the corner (111) direction. At a small dipole moment, the
      superballs are translationally and orientationally disordered, and the dipoles
      become partially orientationally ordered in the presence of the field parallel to
      the plane of the superballs. At a large dipole moment, chains of superballs are
      formed, and the chains become parallel in the presence of the field. The chains
      remain separated for the dipole in the 001-direction and form bundles for the 011
      and 111-directions. The different structures obtained for the different dipole
      directions are interpreted in terms of how compatible the dipole-dipole
      interaction is with the cube-cube interaction at short separation for the
      different directions of the dipole moment. Hence, the structural richness arises
      from an interplay of the different symmetries of a cube and of the field of a
      dipole. 

PMID- 25869764
TI  - Theoretical methods for vibrational spectroscopy and collision induced
      dissociation in the gas phase.
AB  - In this chapter we review recent advances in theoretical methods to understand
      and rationalize anharmonic vibrational spectroscopy (IR-MPD and IR-PD) and
      collision induced dissociations (CID) in the gas phase. We focused our attention
      on the application of molecular dynamics-based methods. DFT-based molecular
      dynamics was shown to be able to reproduce InfraRed Multi-Photon Dissociation (IR
      MPD) and InfraRed Pre-Dissociation (IR-PD) action spectroscopy experiments, and
      help assign the vibrational bands, taking into account finite temperature,
      conformational dynamics, and various anharmonicities. Crucial examples of
      dynamical vibrational spectroscopy are given on the protonated Ala n H(+) series
      (related to IR-MPD in the 800-4,000 cm(-1) domain), ionic clusters (related to IR
      PD in the 3,000-4,000 cm(-1) region), and neutral peptides (related to IR-MPD in
      the far-IR). We give examples from simple (e.g., cationized urea) to more complex
      (e.g., peptides and carbohydrates) molecular systems where molecular dynamics was
      particularly suited to understanding CID experiments.

PMID- 25869765
TI  - Putting patient care back in focus.

PMID- 25869766
TI  - Transnational surrogacy - reproductive rights for whom?

PMID- 25869767
TI  - Projecting human pharmacokinetics of monoclonal antibodies from nonclinical data:
      comparative evaluation of prediction approaches in early drug development.
AB  - Currently, more than 350 monoclonal antibodies (mAbs) and mAb derivatives are
      under development as therapeutics. The prediction of mAb pharmacokinetics
      (PK)/pharmacodynamics (PD) plays a key role in starting dose selection for first
      in-human (FIH) studies. This article presents a brief overview of the biology and
      mechanisms of absorption, distribution, metabolism and excretion (ADME) for mAbs.
      In addition, a detailed review of mAb human PK/PD prediction from nonclinical
      data is provided, including allometry for mAbs with linear or nonlinear PK,
      species-invariant time method, physiologically based PK (PBPK) modeling and
      target-mediated drug disposition (TMDD) model, bioavailability projection and
      immunogenicity impact on PK prediction. Finally, from an industry perspective a
      decision tree of mAb human PK projection is proposed to facilitate drug
      development.

PMID- 25869768
TI  - Saccharothriolides A-C, novel phenyl-substituted 10-membered macrolides isolated
      from a rare actinomycete Saccharothrix sp.
AB  - Three new 10-membered macrolides, saccharothriolides A-C (1-3), were discovered
      from a rare actinomycete Saccharothrix sp. A1506. All of the sp(3) carbons in the
      10-membered ring had chirality, which was determined by extensive spectroscopic
      analysis and TDDFT-calculation of ECD spectra. Saccharothriolide B (2) exhibited
      cytotoxicity against human tumor cell lines HeLa and HT1080. 

PMID- 25869769
TI  - Activity of the novel dual phosphatidylinositol 3-kinase/mammalian target of
      rapamycin inhibitor NVP-BEZ235 against osteosarcoma.
AB  - Recent studies have identified that constitutively active phosphatidylinositol 3
      kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling is an important
      feature of osteosarcoma, where it promotes cell proliferation, survival, and
      chemo-resistance. Here, we studied the therapeutic potential of NVP-BEZ235, a
      novel dual PI3K/mTOR dual inhibitor, on osteosarcoma cells in vivo and in vitro.
      NVP-BEZ235 was cytotoxic and cytostatic to a panel of osteosarcoma lines (MG-63,
      U2OS and SaOs-2), where it induce apoptosis and cell-cycle arrest. At the
      molecular level, NVP-BEZ235 inhibited PI3K-AKT-mTORC1 activation and
      downregulated cyclin D1/cyclin B1 expressions, while increasing MEK/Erk
      phosphorylation in osteosarcoma cells. MEK/Erk inhibitors PD98059 and MEK-162
      increased NVP-BEZ235 activity on osteosarcoma cells. In vivo, oral NVP-BEZ235
      inhibited U2OS xenograft in SCID mice, and its anti-tumor efficiency was further
      enhanced by MEK-162 co-administration. Taken together, our findings indicate that
      dual inhibition of PI3K and mTOR with NVP-BEZ235, either alone or in combination
      with MEK/Erk inhibitors, may be an efficient treatment for osteosarcoma. 

PMID- 25869770
TI  - Very early mobilization in stroke patients treated with intravenous recombinant
      tissue plasminogen activator.
AB  - BACKGROUND: There are limited prospective data on the relative safety of very
      early mobilization of stroke patients after intravenous recombinant tissue
      plasminogen activator (IV rtPA) in stroke patients. We hypothesized that very
      early patient mobilization within 24 hours after IV rtPA administration for acute
      ischemic stroke would be safe and feasible. METHODS: The study was a prospective
      observational safety and feasibility study involving very early mobilization of
      stroke patients by physical therapy/occupational therapy within 24 hours after IV
      rtPA administration for treatment of ischemic stroke. A premobilization safety
      checklist was completed before mobilization to ensure hemodynamic stability. We
      assessed adverse safety events, including changes in patient symptoms, changes in
      vital signs, and bleeding complications. RESULTS: Eighteen patients were enrolled
      in the study, and informed consent was obtained. One hundred percent of patients
      were evaluated with a premobilization safety checklist; 72.2% (13 of 18) were
      mobilized without any adverse event. Eighty-nine percent (42 of 47) of
      mobilization activities were tolerated without an adverse response. One patient
      was orthostatic, and 1 patient had transient worsening of hemiparesis. No patient
      had intracranial bleeding or permanent worsening of neurologic deficits.
      CONCLUSIONS: Very early mobilization within 24 hours of ischemic stroke for
      patients who receive IV rtPA appears to be relatively safe and feasible in most
      patients. Patients who are mobilized within 24 hours of IV rtPA require detailed
      neurologic and vital sign monitoring.

PMID- 25869771
TI  - The Effect of Anemia on the Functional Outcomes of the Stroke Patients and the
      Efficiency of their Stroke Rehabilitation.
AB  - BACKGROUND: There has been limited study focusing on the functional outcomes of
      stroke patients' after rehabilitation, such as functional improvement and
      discharge destination, length of stay (LOS), and complication rate. METHODS: A
      retrospective study was conducted on 123 consecutive patients who were admitted
      to The Prince Charles Hospital Rehabilitation Unit from January 2011 to December
      2012 with clinically defined stroke syndromes. Functional Independence Measure
      (FIM) score was used to measure the functional improvement. Anemia is defined by
      using the World Health Organization's criteria (hemoglobin concentration in men
      <120 mg/dL and in women <110 mg/dL). RESULTS: During the 2-year period, of the
      123 stroke patients, 33 were found to be anemic (26.8%). The demographic factors,
      baseline admission FIM score, comorbidities, and the types of stroke were all
      comparable in both anemic and nonanemic groups. It was found that, when selecting
      only the patients with ischemic stroke for comparison (103 patients), there was a
      significantly higher FIM score improvement (discharge FIM - admission FIM) in
      nonanemic group (P = .042). FIM efficiency (FIM change/LOS) was also
      significantly higher in the nonanemic group (P = .027). Higher percentage of
      patients were discharged home in nonanemic group (94.3% versus 73.3%, P = .006).
      In addition, higher rate of complications was found in anemic group (60% versus
      39%, P = .049). CONCLUSIONS: Anemia appears to have a significant effect on the
      functional improvement and discharge outcomes for patients who had an ischemic
      stroke. Anemia may also increase the complication rate and affect the efficiency
      of stroke rehabilitation for those patients.

PMID- 25869772
TI  - Is Bridging Necessary? A Pilot Study of Bridging versus Primary Stentriever-Based
      Endovascular Reperfusion in Large Anterior Circulation Strokes.
AB  - BACKGROUND: We aimed to determine whether bridging provides additional benefits
      over primary stentriever-based endovascular reperfusion (SER) in patients with
      proximal middle cerebral artery (pMCA) strokes. METHODS: Clinical and radiologic
      data from consecutive stroke patients with large anterior circulation infarcts
      involving the pMCA were analyzed. Stroke subtypes were categorized according to
      Trial of ORG 10172 in Acute Stroke Treatment criteria. Neurologic deficits were
      assessed with the National Institutes of Health Stroke Scale (NIHSS), and vessel
      recanalization was determined using the Thrombolysis in Cerebral Infarction scale
      at the end of SER. Good outcome was defined as a modified Rankin Scale (mRS)
      score of 2 or lesser. RESULTS: Fifty-seven patients with a median age of 66 years
      were included. Of those, 24 received prior systemic tissue plasminogen activator
      and 33 received primary SER. Atrial fibrillation was more common in patients who
      underwent SER but there were no other between-group differences in baseline
      variables, procedure-related variables, or outcome parameters. Six patients died
      and 27 patients achieved an mRS of 2 or less at 90 days. Patients who were
      treated with tPA before SER needed less stentriever passes to recanalize the
      occluded vessel, but bridging did not impact the chances for either survival or
      favorable outcome. Age (odds ratio [OR], .92; 95% confidence interval [CI], .85
      .98) and NIHSS score (OR, .12; 95% CI, .02-.78) were the only variables
      associated with outcome on multivariate analysis. CONCLUSIONS: Primary SER and
      bridging resulted in equally high survival and good outcome rates. Our results
      suggest that the benefits of primary SER in such critically ill patients may
      bypass the need for bridging therapy and merit further study.

PMID- 25869773
TI  - Predictive value of high residual platelet reactivity by flow cytometry for
      outcomes of ischemic stroke patients on clopidogrel therapy.
AB  - High residual platelet reactivity (HRPR) assessed by multiple tests has been
      associated with worse clinical outcomes. However, the clinical impact of HRPR
      assessed by flow cytometry is unknown. The aim of this study was to validate the
      predictive value of HRPR measured by flow cytometry for clinical outcomes in
      ischemic stroke patients during clopidogrel therapy. Overall, 198 consecutive
      patients with ischemic stroke taking clopidogrel underwent platelet function
      testing on flow cytometer including adenosine diphosphate (ADP)-induced platelet
      aggregation (PAg) and platelet activation markers (CD62P, CD63, and PAC-1). Poor
      outcome was defined as poor prognosis and ischemic events during 12-month follow
      up. By receiver operating characteristic curve analysis, residual platelet
      reactivity assessed by flow cytometry was able to distinguish between patients
      with and without poor outcomes, when platelet inhibition was evaluated with ADP
      PAg (area under the curve [AUC], .77; 95% confidence interval [CI], .69-.84; P <
      .001), CD62P (AUC, .73; 95% CI, .64-.81; P < .001), CD63 (AUC, .72; 95% CI, .64
      .80; P < .001), and PAC-1 (AUC, .70; 95% CI, .62-.78; P < .001). The prevalence
      of HRPR was 25.8% for ADP-PAg, 32.8% for CD62P, 41.4% for CD63, and 56.1% for PAC
      1. The multiple logical regression analysis demonstrated that HRPR was an
      independent predictor of poor outcomes (ADP-PAg: odds ratio [OR] 13.03, 95% CI
      5.66-29.98, P < .001; CD62P: OR 8.55, 95% CI 3.94-18.57, P < .001; CD63: OR 8.74,
      95% CI 3.89-19.64, P < .001; PAC-1: OR 4.23, 95% CI 1.98-9.08). In conclusion,
      HRPR, assessed by flow cytometry, is able to detect ischemic stroke patients at
      increased risk of 12-month poor outcomes on clopidogrel treatment. 

PMID- 25869774
TI  - Rapidly improving stroke symptoms: a pilot, prospective study.
AB  - BACKGROUND: Rapidly improving stroke symptoms (RISSs) are a controversial
      exclusion for intravenous recombinant tissue plasminogen activator (rt-PA) for
      acute ischemic stroke (AIS). We estimated the frequency of 4 prespecified RISS
      definitions and explored their relationship to clinical outcome. METHODS: Pilot,
      prospective study of AIS patients admitted within 4.5 hours of symptom onset.
      Serial assessments using National Institute of Health Stroke Scale (NIHSS) were
      performed every 20 +/- 5 minutes until a rt-PA treatment decision was made,
      independent of the study. Improvement was calculated as the difference between
      baseline NIHSS and treatment decision NIHSS. RISS was defined as a 4-point or
      greater improvement, 25% or greater, 50% or greater, and according to the
      previously reported TREAT (The Re-examining Acute Eligibility for Thrombolysis)
      criteria. Unfavorable outcome was defined as modified Rankin Scale score more
      than 1 at 90 days after stroke. Logistic regression determined if RISS
      definition(s) related to the outcome. RESULTS: Fifty patients with AIS were
      enrolled: mean age 65 years; median baseline NIHSS score 5 (interquartile range,
      2-11). RISS frequencies were 10%-22% based on definition. Median treatment
      decision NIHSS score is 5 (interquartile range, 2-9). Twenty-three (46%) patients
      received rt-PA. None of the 3 non-TREAT RISS definitions was independently
      associated with the outcome. Five of fifty (10%) were RISS according to the TREAT
      criteria, all 5 had good outcome without rt-PA. CONCLUSIONS: A Serial NIHSS
      assessment before treatment decision is feasible and may help determine the
      frequency and magnitude of RISS. This is the first prospective estimate of RISS
      frequency and outcome according to various prespecified definitions. The TREAT
      RISS frequency as a more restrictive definition may better predict good outcome
      of RISS in future, larger studies.

PMID- 25869775
TI  - Local O2 Balance in Cerebral Ischemia-Reperfusion Improved during Pentobarbital
      Compared with Isoflurane Anesthesia.
AB  - BACKGROUND: Most anesthetics affect cerebral blood flow and metabolism. We
      compared microregional O2 balance in cerebral ischemia-reperfusion during
      pentobarbital and isoflurane anesthesia. METHODS: After 1 hour of middle cerebral
      artery occlusion and a 2-hour reperfusion under isoflurane (1.4%, n = 14) or
      pentobarbital (50 mg/kg, n = 14) anesthesia in rats, regional cerebral blood flow
      using (14)C-iodoantipyrine autoradiography, microregional arterial and venous O2
      saturation (20-60 MUm in diameter) using cryomicrospectrophotometry, and the size
      of cortical infarct were determined. RESULTS: Ischemia-reperfusion decreased the
      average cortical venous O2 saturation in both pentobarbital and isoflurane groups
      (P < .0001), which was higher (P < .05) with pentobarbital despite a similar
      average regional cerebral blood flow and O2 consumption. The heterogeneity of
      venous O2 saturation reported as a coefficient of variation (100 * standard
      deviation/mean) was smaller (P < .005) with pentobarbital than that with
      isoflurane (7.5 versus 16.1). The number of veins with low venous O2 saturation
      (<50%) was smaller (P < .005) with pentobarbital (5 of 80 versus 24 of 80). The
      percentage of cortical infarct in total cortex was smaller with pentobarbital
      (5.2 +/- 2.5% versus 12.3 +/- 2.6%, P < .001). CONCLUSIONS: In the cerebral
      ischemic-reperfused cortex, the average venous O2 saturation was higher, and its
      heterogeneity and the number of veins with low O2 saturation were smaller under
      pentobarbital than isoflurane anesthesia. This improvement in microregional O2
      balance with pentobarbital was accompanied by the reduced cortical infarct. Our
      data suggest that the neurologic outcome could vary during cerebral ischemia
      reperfusion depending on the anesthetics used.

PMID- 25869776
TI  - Posterior Reversible Encephalopathy Syndrome in a Child Stung by Androctonus
      mauretanicus Scorpion.
AB  - Posterior reversible encephalopathy syndrome (PRES) after scorpion sting was very
      rarely reported in literature. This is an authenticated report of PRES occurring,
      in a 3-year-old previously healthy girl, as a complication of the Moroccan
      Androctonus mauretanicus sting. According to the available and recent data, we
      attempt to discuss the potential mechanisms leading to this neurologic disorder
      and to determine the possible cause-effect relationship between scorpion venom
      and its development. 

PMID- 25869777
TI  - Tocilizumab for Treating Takayasu's Arteritis and Associated Stroke: A Case
      Series and Updated Review of the Literature.
AB  - BACKGROUND: Takayasu's arteritis (TA) is a rare inflammatory disease that can
      result in stroke. Treatment of patients with TA requires prolonged use of
      corticosteroids (CS). We assessed the effectiveness of tocilizumab (TCZ) in
      inducing disease remission and reducing CS doses in patients with TA. METHODS: We
      retrospectively reviewed all patients with TA treated with TCZ and determined
      their response to therapy and adverse effects. We also summarized all reported TA
      patients treated with TCZ in the literature (both PubMed and MEDLINE) with no
      date or language restrictions and determined the utility of TCZ in inducing
      remission, acting as a CS sparing agent, and its adverse effects. RESULTS: TCZ
      induced remission and reduction of CS doses in all 3 cases of TA in our cohort.
      Remission was achieved in 2 patients where stroke was the initial manifestation
      of active TA. In total, 3 of 4 patients with TA and stroke (2 from our study and
      2 from other studies) treated with TCZ achieved remission and stability of their
      disease. We also identified 30 patients with TA treated with TCZ in the
      literature, of which 76.7% achieved remission despite the lack of sustained
      remission with other biological agents. In addition, TCZ resulted in a
      statistically significant reduction of CS in patients on CS before using TCZ
      (median, -8.8 mg/day; interquartile range, -19.4, to -3.4 mg/day; Wilcoxon P
      value, .0002). CONCLUSIONS: TCZ is a promising alternative for treating TA
      refractory to other biologics and for TA patients with stroke.

PMID- 25869778
TI  - Contrasting regulation of macrophage iron homeostasis in response to infection
      with Listeria monocytogenes depending on localization of bacteria.
AB  - Due to its multiple roles for the proliferation and pathogenicity of many
      microbes on the one hand and via modulation of immune effector functions on the
      other hand the control over iron homeostasis is thought to play a decisive role
      in the course of infections. Diversion of cellular iron traffic is considered as
      an important defense mechanism of macrophages to reduce metal availability for
      intracellular bacteria residing in the phagosome. However, evidence is lacking
      whether such alterations of iron homeostasis also become evident upon infection
      with bacteria gaining access to the cytosol like Listeria monocytogenes. Here we
      show that infection of macrophages with L. monocytogenes triggers the expression
      of the major cellular iron exporter ferroportin1 and induces cellular iron
      egress. As the growth of Listeria within macrophages is promoted by iron,
      stimulation of ferroportin1 functionality limits the availability of the metal
      for Listeria residing in the cytoplasm, whereas ferroportin1 degradation upon
      hepcidin treatment increases intracellular bacterial growth. In parallel to an
      increase of ferroportin1 expression, infected macrophages induce anti-microbial
      immune effector mechanisms such as TNFalpha formation or NO expression which are
      aggravated upon iron deficiency. These adaptive changes of iron homeostasis and
      immune response pathways are only found in macrophages infected with Listeria
      which express listeriolysin O and are therefore able to escape from the phagosome
      to the cytoplasm. Listeriolysin O deficient Listeria which are restricted to the
      phagosome are even killed by excess iron which may be based on "iron
      intoxification" via macrophage radical formation, because iron supplementation in
      that setting is paralleled by increased ROS formation. Our results indicate that
      ferroportin1 mediated iron export is a nutritional immune effector pathway to
      control infection with Listeria residing in the cytoplasm, whereas a different
      strategy is observed in mutant Listeria restricted to the phagosome, where iron
      remains in the macrophages likewise contributing to ROS mediated intoxification
      of bacteria. 

PMID- 25869779
TI  - Simultaneous DNP enhancements of (1)H and (13)C nuclei: theory and experiments.
AB  - DNP on heteronuclear spin systems often results in interesting phenomena such as
      the polarization enhancement of one nucleus during MW irradiation at the
      "forbidden" transition frequencies of another nucleus or the polarization
      transfer between the nuclei without MW irradiation. In this work we discuss the
      spin dynamics in a four-spin model system of the form {ea-eb-((1)H,(13)C)}, with
      the Larmor frequencies omegaa, omegab, omegaH and omegaC, by performing Liouville
      space simulations. This spin system exhibits the common (1)H solid effect (SE),
      (13)C cross effect (CE) and in addition high order CE-DNP enhancements. Here we
      show, in particular, the "proton shifted (13)C-CE" mechanism that results in
      (13)C polarization when the model system, at one of its (13)C-CE conditions, is
      excited by a MW field at the zero quantum or double quantum electron-proton
      transitions omegaMW = omegaa +/- omegaH and omegaMW = omegab +/- omegaH.
      Furthermore, we introduce the "heteronuclear" CE mechanism that becomes efficient
      when the system is at one of its combined CE conditions |omegaa - omegab| =
      |omegaH +/- omegaC|. At these conditions, simulations of the four-spin system
      show polarization transfer processes between the nuclei, during and without MW
      irradiation, resembling the polarization exchange effects often discussed in the
      literature. To link the "microscopic" four-spin simulations to the experimental
      results we use DNP lineshape simulations based on "macroscopic" rate equations
      describing the electron and nuclear polarization dynamics in large spin systems.
      This approach is applied based on electron-electron double resonance (ELDOR)
      measurements that show strong (1)H-SE features outside the EPR frequency range.
      Simulated ELDOR spectra combined with the indirect (13)C-CE (iCE) mechanism,
      result in additional "proton shifted (13)C-CE" features that are similar to the
      experimental ones. These features are also observed experimentally in (13)C-DNP
      spectra of a sample containing 15 mM of trityl in a glass forming solution of
      (13)C-glycerol/H2O and are analyzed by calculating the basic (13)C-SE and (13)C
      iCE shapes using simulated ELDOR spectra that were fitted to the experimental
      ones. 

PMID- 25869781
TI  - ANZSNM - 45th Annual Scientific Meeting, Brisbane, April 17-20, 2015 - 'Wheel of
      Change'.

PMID- 25869782
TI  - Liverpool CCG rethinks funding of homeopathy.

PMID- 25869780
TI  - Flupirtine attenuates chronic restraint stress-induced cognitive deficits and
      hippocampal apoptosis in male mice.
AB  - Chronic restraint stress (CRS) causes hippocampal neurodegeneration and
      hippocampus-dependent cognitive deficits. Flupirtine represents neuroprotective
      effects and we have previously shown that flupirtine can protect against memory
      impairment induced by acute stress. The present study aimed to investigate
      whether flupirtine could alleviate spatial learning and memory impairment and
      hippocampal apoptosis induced by CRS. CRS mice were restrained in well-ventilated
      Plexiglass tubes for 6h daily beginning from 10:00 to 16:00 for 21 consecutive
      days. Mice were injected with flupirtine (10mg/kg and 25mg/kg) or vehicle (10%
      DMSO) 30min before restraint stress for 21 days. After stressor cessation, the
      spatial learning and memory, dendritic spine density, injured neurons and the
      levels of Bcl-2, Bax, p-Akt, p-GSK-3beta, p-Erk1/2 and synaptophysin of
      hippocampal tissues were examined. Our results showed that flupirtine
      significantly prevented spatial learning and memory impairment induced by CRS in
      the Morris water maze. In addition, flupirtine (10mg/kg and 25mg/kg) treatment
      alleviated neuronal apoptosis and the reduction of dendritic spine density and
      synaptophysin expression in the hippocampal CA1 region of CRS mice. Furthermore,
      flupirtine (10mg/kg and 25mg/kg) treatment significantly decreased the expression
      of Bax and increased the p-Akt and p-GSK-3beta, and flupirtine (25mg/kg)
      treatment up-regulated the p-Erk1/2 in the hippocampus of CRS mice. These results
      suggested that flupirtine exerted protective effects on the CRS-induced cognitive
      impairment and hippocampal neuronal apoptosis, which is possibly associated with
      the activation of Akt/GSK-3beta and Erk1/2 signaling pathways. 

PMID- 25869784
TI  - Neuroanatomy of Alzheimer's Disease and Late-Life Depression: A Coordinate-Based
      Meta-Analysis of MRI Studies.
AB  - Depression and cognitive impairment are both common disorders in elderly people
      and frequently occur together. Due to the presence of a common set of behavioral
      and cognitive symptoms, differential diagnosis may become arduous. Neuroimaging
      may offer a good tool during diagnosis. We performed a coordinate-based meta
      analysis to compare gray matter changes in Alzheimer's disease (AD) and late-life
      depression (LLD). AD and LLD led to brain atrophy in networks only partially
      overlapping. Both conditions are linked to a reduction of the bilateral
      hippocampal volume, but AD is correlated with great atrophy in the left anterior
      hippocampus and bilateral posterior cingulate cortex, while LLD is correlated
      with great atrophy in the precuneus, superior frontal gyrus, and ventromedial
      frontal cortex. Present results shed some light on neural underpinnings of AD and
      LLD and provide new useful evidence for differential diagnosis. 

PMID- 25869783
TI  - Predicting Alzheimer's Disease Using Combined Imaging-Whole Genome SNP Data.
AB  - The growing public threat of Alzheimer's disease (AD) has raised the urgency to
      discover and validate prognostic biomarkers in order to predicting time to onset
      of AD. It is anticipated that both whole genome single nucleotide polymorphism
      (SNP) data and high dimensional whole brain imaging data offer predictive values
      to identify subjects at risk for progressing to AD. The aim of this paper is to
      test whether both whole genome SNP data and whole brain imaging data offer
      predictive values to identify subjects at risk for progressing to AD. In 343
      subjects with mild cognitive impairment (MCI) enrolled in the Alzheimer's Disease
      Neuroimaging Initiative (ADNI-1), we extracted high dimensional MR imaging
      (volumetric data on 93 brain regions plus a surface fluid registration based
      hippocampal subregion and surface data), and whole genome data (504,095 SNPs from
      GWAS), as well as routine neurocognitive and clinical data at baseline. MCI
      patients were then followed over 48 months, with 150 participants progressing to
      AD. Combining information from whole brain MR imaging and whole genome data was
      substantially superior to the standard model for predicting time to onset of AD
      in a 48-month national study of subjects at risk. Our findings demonstrate the
      promise of combined imaging-whole genome prognostic markers in people with mild
      memory impairment.

PMID- 25869786
TI  - Olfactory Dysfunction in ApoE E4/4 Homozygotes with Alzheimer's Disease.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder characterized by
      progressive memory impairment and the presence of amyloid plaques and
      neurofibrillary tangles. The associated neuropathology originates in brain areas
      responsible for olfaction, which makes olfactory tasks potentially useful for
      assessing AD. The strongest genetic risk factor for AD is the apolipoprotein E
      (ApoE) E4 allele that has been associated with increased cognitive and olfactory
      deficits. While individuals carrying one E4 allele of the ApoE gene are at
      increased risk for AD relative to non-carriers, those with two copies of the E4
      allele demonstrate an even higher risk for developing AD. Furthermore, homozygous
      ApoE E4/4 individuals diagnosed with AD are known to have heightened amyloid
      burden and a more rapid rate of cognitive decline relative to heterozygous E3/4
      ApoE carriers. All of these factors suggest there are differences in severity and
      progression of AD as a function of possessing one versus two E4 alleles. The
      current study investigated olfactory functioning in homozygous E4/4 older adults
      diagnosed with probable AD. Compared to demographically matched E3/3 and E3/4
      individuals, E4/4 individuals showed deficits in odor identification and remote
      odor memory as measured by odor familiarity ratings. The current findings suggest
      that these particular domains of olfactory functioning may be more impaired in AD
      E4/4 homozygotes compared to E3/4 heterozygotes and E3/3 homozygotes. These
      deficits give insight into how the presence of two E4 alleles may differentially
      affect the progression of AD and suggest the usefulness of odor tasks in
      detecting those at risk for AD.

PMID- 25869785
TI  - The GLP-1 Receptor Agonist Liraglutide Improves Memory Function and Increases
      Hippocampal CA1 Neuronal Numbers in a Senescence-Accelerated Mouse Model of
      Alzheimer's Disease.
AB  - Recent studies indicate that glucagon-like peptide 1 (GLP-1) receptor agonists,
      currently used in the management of type 2 diabetes, exhibit neurotrophic and
      neuroprotective effects in amyloid-beta (Abeta) toxicity models of Alzheimer's
      disease (AD). We investigated the potential pro-cognitive and neuroprotective
      effects of the once-daily GLP-1 receptor agonist liraglutide in senescence
      accelerated mouse prone 8 (SAMP8) mice, a model of age-related sporadic AD not
      dominated by amyloid plaques. Six-month-old SAMP8 mice received liraglutide (100
      or 500 MUg/kg/day, s.c.) or vehicle once daily for 4 months. Vehicle-dosed age
      matched 50% back-crossed as well as untreated young (4-month-old) SAMP8 mice were
      used as control groups for normal memory function. Vehicle-dosed 10-month-old
      SAMP8 mice showed significant learning and memory retention deficits in an active
      avoidance T-maze, as compared to both control groups. Also, 10-month-old SAMP8
      mice displayed no immunohistological signatures of amyloid-beta plaques or
      hyperphosphorylated tau, indicating the onset of cognitive deficits prior to
      deposition of amyloid plaques and neurofibrillary tangles in this AD model.
      Liraglutide significantly increased memory retention and total hippocampal CA1
      pyramidal neuron numbers in SAMP8 mice, as compared to age-matched vehicle-dosed
      SAMP8 mice. In conclusion, liraglutide delayed or partially halted the
      progressive decline in memory function associated with hippocampal neuronal loss
      in a mouse model of pathological aging with characteristics of neurobehavioral
      and neuropathological impairments observed in early-stage sporadic AD. 

PMID- 25869787
TI  - Acute Exposure of the Mediobasal Hypothalamus to Amyloid-beta25-35 Perturbs
      Hepatic Glucose Metabolism.
AB  - Patients with Alzheimer's disease (AD) have a higher risk for developing insulin
      resistance and diabetes. Amyloid plaques, a hallmark of AD, are composed of
      amyloid-beta (Abeta). Because the mediobasal hypothalamus controls hepatic
      glucose production, we examined the hypothesis that its exposure to Abeta
      perturbs the regulation of glucose metabolism. The infusion of Abeta25-35, but
      not its scrambled counterpart, into the mediobasal hypothalamus of young rats,
      increased circulating glucose as a consequence of enhanced hepatic glucose
      production during pancreatic clamp studies. These findings suggest a link between
      AD and alterations of glucose metabolism. 

PMID- 25869788
TI  - Correcting for the Absence of a Gold Standard Improves Diagnostic Accuracy of
      Biomarkers in Alzheimer's Disease.
AB  - BACKGROUND: Studies investigating the diagnostic accuracy of biomarkers for
      Alzheimer's disease (AD) are typically performed using the clinical diagnosis or
      amyloid-beta positron emission tomography as the reference test. However, neither
      can be considered a gold standard or a perfect reference test for AD. Not
      accounting for errors in the reference test is known to cause bias in the
      diagnostic accuracy of biomarkers. OBJECTIVE: To determine the diagnostic
      accuracy of AD biomarkers while taking the imperfectness of the reference test
      into account. METHODS: To determine the diagnostic accuracy of AD biomarkers and
      taking the imperfectness of the reference test into account, we have developed a
      Bayesian method. This method establishes the biomarkers' true value in predicting
      the AD-pathology status by combining the reference test and the biomarker data
      with available information on the reliability of the reference test. The new
      methodology was applied to two clinical datasets to establish the joint accuracy
      of three cerebrospinal fluid biomarkers (amyloid-beta 1 - 42, Total tau, and P
      tau181p) by including the clinical diagnosis as imperfect reference test into the
      analysis. RESULTS: The area under the receiver-operating-characteristics curve to
      discriminate between AD and controls, increases from 0.949 (with 95% credible
      interval [0.935,0.960]) to 0.990 ([0.985,0.995]) and from 0.870 ([0.817,0.912])
      to 0.975 ([0.943,0.990]) for the cohorts, respectively. CONCLUSIONS: Use of the
      Bayesian methodology enables an improved estimate of the exact diagnostic value
      of AD biomarkers and overcomes the lack of a gold standard for AD. Using the new
      method will increase the diagnostic confidence for early stages of AD.

PMID- 25869789
TI  - Structural basis for regulation of stability and activity in glyceraldehyde-3
      phosphate dehydrogenases. Differential scanning calorimetry and molecular
      dynamics.
AB  - Tissue specific isoforms of human glyceraldehyde-3-phosphate dehydrogenase,
      somatic (GAPD) and sperm-specific (GAPDS), have been reported to display
      different levels of both stability and catalytic activity. Here we apply MD
      simulations to investigate molecular basis of this phenomenon. The protein is a
      tetramer where each subunit consists of two domains - catalytic and NAD-binding
      one. We demonstrated key residues responsible for intersubunit and interdomain
      interactions. Effect of several residues was studied by point mutations. Overall
      we considered three mutations (Glu96Gln, Glu244Gln and Asp311Asn) disrupting
      GAPDS-specific salt bridges. Comparison of calculated interaction energies with
      calorimetric enthalpies confirmed that intersubunit interactions were responsible
      for enhanced thermostability of GAPDS whereas interdomain interactions had
      indirect influence on intersubunit contacts. Mutation Asp311Asn was around 10A
      far from the active center and corresponded to the closest natural substitution
      in the isoenzymes. MD simulations revealed that this residue had slight
      interaction with catalytic residues but influenced the hydrogen bond net and
      dynamics in active site. These effects can be responsible for a strong influence
      of this residue on catalytic activity. Overall, our results provide new insight
      into glyceraldehyde-3-phosphate dehydrogenase structure-function relationships
      and can be used for the engineering of mutant proteins with modified properties
      and for development of new inhibitors with indirect influence on the catalytic
      site. 

PMID- 25869790
TI  - Technology. Breaking Mendelian inheritance with CRISPR-Cas.

PMID- 25869791
TI  - [Trichobezoars: An unusual cause of intestinal obstruction].

PMID- 25869792
TI  - [Nutritional composition of infant milk formulas. Level of compliance in their
      manufacture and adequacy of nutritional needs].
AB  - INTRODUCTION: A high percentage of infants are fed with infant formulas. The aim
      of this study was to assess compliance with the Technical and Safety Regulations
      in the manufacture of Spanish infant formulas, analyse their adequacy to the
      recommendations of nutritional composition and the Dietary References Intakes for
      infants. MATERIALS AND METHODS: A total of 31 infant formulas were analysed, of
      which 18 were infant formulas, 10 follow-on formulas, and 3 growing-up milks. The
      European Technical and Safety Regulations, the Spanish Dietary Reference Intakes
      and the Institute of Medicine of the United States and Canada, were used for the
      assessment of compliance and adequacy. RESULTS: The energy and macronutrient
      content of analysed infant formulas is placed in the middle of the range
      indicated in the Technical and Safety Regulations, and meets the recommended
      amounts. However, most micronutrients such as phosphorus, calcium, retinol,
      vitamin D, E, C, B6, B12, thiamin, riboflavin, and folate are at the lower limit
      of the Technical and Safety Regulations. However, the recommended consumption of
      infant formulas exceeded the Dietary References Intakes for vitamin E, C,
      retinol, vitamin B and folate, and vitamin B12 for follow-on formulas.
      CONCLUSIONS: Infant formulas are within the reference values of the European
      Technical and Safety Regulations in energy and macronutrients, but we believe
      that the level of micronutrients should be reviewed, based on current scientific
      data on infant requirements and possible adverse effects.

PMID- 25869793
TI  - [Home births under debate].

PMID- 25869794
TI  - Crescentic and necrotising glomerulonephritis: a rare histological manifestation
      of Alport syndrome.

PMID- 25869795
TI  - Pseudorabies virus US3 leads to filamentous actin disassembly and contributes to
      viral genome delivery to the nucleus.
AB  - The conserved alphaherpesvirus US3 tegument protein induces rearrangements of the
      actin cytoskeleton, consisting of protrusion formation and stress fiber
      breakdown. Although US3 does not affect levels of total actin protein, it remains
      unclear whether US3 modulates the total levels of filamentous (F) actin. In this
      report, we show that the pseudorabies virus (PRV) US3 protein, via its kinase
      activity, leads to disassembly of F-actin in porcine ST cells. F-actin
      disassembly has been reported before to contribute to host cell entry of HIV. In
      line with this, in the current study, we report that US3 has a previously
      uncharacterized role in viral genome delivery to the nucleus, since quantitative
      polymerase chain reaction (qPCR) assays on nuclear fractions demonstrated a
      reduced nuclear delivery of US3null PRV compared to wild type PRV genomes.
      Treatment of cells with the actin depolymerizing drug cytochalasin D enhanced
      virus genome delivery to the nucleus, particularly of US3null PRV, supporting a
      role for F-actin disassembly during certain aspects of viral entry. In
      conclusion, the US3 kinase of PRV leads to F-actin depolymerization, and US3 and
      F-actin disassembly contribute to viral genome delivery to the nucleus. 

PMID- 25869796
TI  - Joint effects between urinary selenium and polymorphisms in methylation related
      genes on breast cancer risk.
AB  - The aim of this study was to explore the associations of urinary selenium and
      polymorphisms in methylation related genes with breast cancer risk and the
      interactions on the risk. The present study involved in 240 female patients with
      incident breast cancer and 246 age-matched controls in two affiliated hospitals
      of Sun Yat-sen University in Guangzhou, China, from October 2009 to July 2010.
      DNMT1 rs2228611, MTHFR rs1801133, and MTR rs1805087 were genotyped using a matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry platform.
      Urinary concentration of selenium was measured by inductively coupled plasma mass
      spectrometry. Women with urinary selenium in the second tertile had a significant
      reduced breast cancer risk compared to those with urinary selenium in the lowest
      tertile [OR (95%CI): 0.50 (0.30, 0.81)]. DNMT1 rs2228611, MTHFR rs1801133, and
      MTR rs1805087 were not associated with breast cancer risk. Women with the third
      tertile of urinary selenium had a significant reduced breast cancer risk compared
      to those with the lowest tertile among women only with CC genotype [OR (95%CI):
      0.55 (0.30, 1.00)] but not CT/TT genotypes [OR (95%CI): 1.58 (0.73, 3.42)] of
      MTHFR rs1801133 (P for interaction=0.044). Our results suggested that selenium
      was associated with a decreased risk of breast cancer and this beneficial effect
      was limited to women with CC genotype of MTHFR rs1801133. 

PMID- 25869797
TI  - Fluorescence analysis of urine and its potential for ovarian cancer screening.
AB  - Early diagnosis of ovarian cancer could lead to decreased mortality. We assessed
      the possible use of urine autofluorescence analysis in its diagnostics and
      screening.We analysed urine from 42 healthy volunteers, 35 patients with benign,
      and 36 patients with malignant ovarian tumors. Synchronous fluorescence spectra
      with a 70 nm wavelength difference were recorded for (1:1 - 1:1024) urine
      dilutions. Concentration matrices of synchronous spectra (CMSS) were used to
      classify samples into tested groups.CMSS analysis allowed us to distinguish
      patients with malignant tumors from healthy ones with a high sensitivity (91.67
      %) and specificity (100 %), a positive predictive value (PPV) 100 % and a
      negative predictive value (NPV) 93.33 %. However, discrimination between benign
      and malignant ovarian tumors was weaker, with sensitivity 86.11 %, specificity
      77.14 %, PPV 79.49 % and NPV 84.38 %. Fluorescence intensity and the position of
      peaks at 330 and 360 nm were found to be associated with the grade and stage,
      suggesting that different fluorescent metabolites may prevail at different stages
      of the disease.CMSS analysis of urine provides an alternative for ovarian cancer
      screening method development and could be used as a diagnostic test to detect the
      recurrence of the disease after therapy. 

PMID- 25869798
TI  - Simultaneous analysis of multiple neurotransmitters by hydrophilic interaction
      liquid chromatography coupled to tandem mass spectrometry.
AB  - Neurotransmitters are endogenous metabolites that allow the signal transmission
      across neuronal synapses. Their biological role is crucial for many physiological
      functions and their levels can be changed by several diseases. Because of their
      high polarity, hydrophilic interaction liquid chromatography (HILIC) is a
      promising tool for neurotransmitter analysis. Due to the large number of HILIC
      stationary phases available, an evaluation of the column performances and
      retention behaviors has been performed on five different commercial HILIC packing
      materials (silica, amino, amide and two zwitterionic stationary phases). Several
      parameters like the linear correlation between retention and the distribution
      coefficient (logD), the separation factor k and the column resolution Rs have
      been investigated and the column performances have been visualized with a heat
      map and hierarchical clustering analysis. An optimized and validated HILIC-MS/MS
      method based on the ZIC-cHILIC column is proposed for the simultaneous detection
      and quantification of twenty compounds consisting of neurotransmitters,
      precursors and metabolites: 3-methoxytyramine (3-MT), 5-hydroxyindoleacetic acid
      (5-HIAA), 5-hydroxy-L-tripthophan, acetylcholine, choline, L-3,4
      dihydroxyphenylalanine (L-DOPA), dopamine, epinephrine, gamma-aminobutyric acid
      (GABA), glutamate, glutamine, histamine, histidine, L-tryptophan, L-tyrosine,
      norepinephrine, normetanephrine, phenylalanine, serotonin and tyramine. The
      method was applied to neuronal metabolite profiling of the central nervous system
      of the freshwater snail Lymnaea stagnalis. This method is suitable to explore
      neuronal metabolism and its alteration in different biological matrices. 

PMID- 25869799
TI  - A poly(alkyl methacrylate-divinylbenzene-vinylbenzyl trimethylammonium chloride)
      monolithic column for solid-phase microextraction.
AB  - In this study, an organic polymer monolithic columns, which were prepared via in
      situ polymerization of alkyl methacrylate-ester (AMA), divinylbenzene (DVB) and
      vinylbenzyl trimethylammonium chloride (VBTA, charged monomer), were developed as
      adsorbent for solid-phase microextraction (SPME). Different parameters affecting
      the extraction efficiency for nine (9) non-steroidal anti-inflammatory drugs
      (NSAIDs) such as the ratio of the stearyl methacrylate (SMA) to DVB monomer,
      column length, sample pH, extraction flow rate and desorption solvent were
      investigated to obtain the optimal SPME condition. Also, the permeability for
      each poly(AMA-DVB-VBTA) monolithic column was investigated by adding porogenic
      solvent (poly(ethylene glycol), PEG). Using the optimized condition, a series of
      AMA-based poly(AMA-DVB-VBTA) monolith columns were developed to determine the
      effect the extraction efficiency of NSAIDs by varying the alkyl chain length of
      the methacrylate ester (methyl-, butyl-, octyl-, or lauryl-methacrylate; (MMA,
      BMA, OMA, LMA)). Results showed that decreasing the AMA chain length increases
      the extraction efficiency of some NSAIDs (i.e. sulindac (sul), naproxen (nap),
      ketoprofen (ket) and indomethacin (idm)). Among the poly(AMA-DVB-VBTA) monolithic
      columns, poly(BMA-DVB-VBTA) showed a highly repeatable extraction efficiency for
      NSAIDs with recoveries ranging from 85.0 to 100.2% with relative standard
      deviation (RSD) less than 6.8% (n=3). The poly(BMA-DVB-VBTA) can also be reused
      for at least 50 times without any significant effect in extraction efficiency for
      NSAIDs. Finally, using the established conditions, the poly(BMA-DVB-VBTA) was
      used to extract trace-level NSAIDs (100MUgL(-1)) in river water with good
      recoveries ranging from 75.8 to 90.8% (RSD<14.9%). 

PMID- 25869800
TI  - Non-targeted analysis of electronics waste by comprehensive two-dimensional gas
      chromatography combined with high-resolution mass spectrometry: Using accurate
      mass information and mass defect analysis to explore the data.
AB  - Comprehensive two-dimensional gas chromatography (GC*GC) and high-resolution mass
      spectrometry (HRMS) offer the best possible separation of their respective
      techniques. Recent commercialization of combined GC*GC-HRMS systems offers new
      possibilities for the analysis of complex mixtures. However, such experiments
      yield enormous data sets that require new informatics tools to facilitate the
      interpretation of the rich information content. This study reports on the
      analysis of dust obtained from an electronics recycling facility by using GC*GC
      in combination with a new high-resolution time-of-flight (TOF) mass spectrometer.
      New software tools for (non-traditional) Kendrick mass defect analysis were
      developed in this research and greatly aided in the identification of compounds
      containing chlorine and bromine, elements that feature in most persistent organic
      pollutants (POPs). In essence, the mass defect plot serves as a visual aid from
      which halogenated compounds are recognizable on the basis of their mass defect
      and isotope patterns. Mass chromatograms were generated based on specific ions
      identified in the plots as well as region of the plot predominantly occupied by
      halogenated contaminants. Tentative identification was aided by database
      searches, complementary electron-capture negative ionization experiments and
      elemental composition determinations from the exact mass data. These included
      known and emerging flame retardants, such as polybrominated diphenyl ethers
      (PBDEs), hexabromobenzene, tetrabromo bisphenol A and tris (1-chloro-2-propyl)
      phosphate (TCPP), as well as other legacy contaminants such as polychlorinated
      biphenyls (PCBs) and polychlorinated terphenyls (PCTs). 

PMID- 25869801
TI  - Retention prediction and separation optimization under multilinear gradient
      elution in liquid chromatography with Microsoft Excel macros.
AB  - A package of Excel VBA macros have been developed for modeling multilinear
      gradient retention data obtained in single or double gradient elution mode by
      changing organic modifier(s) content and/or eluent pH. For this purpose, ten
      chromatographic models were used and four methods were adopted for their
      application. The methods were based on (a) the analytical expression of the
      retention time, provided that this expression is available, (b) the retention
      times estimated using the Nikitas-Pappa approach, (c) the stepwise approximation,
      and (d) a simple numerical approximation involving the trapezoid rule for
      integration of the fundamental equation for gradient elution. For all these
      methods, Excel VBA macros have been written and implemented using two different
      platforms; the fitting and the optimization platform. The fitting platform
      calculates not only the adjustable parameters of the chromatographic models, but
      also the significance of these parameters and furthermore predicts the analyte
      elution times. The optimization platform determines the gradient conditions that
      lead to the optimum separation of a mixture of analytes by using the Solver
      evolutionary mode, provided that proper constraints are set in order to obtain
      the optimum gradient profile in the minimum gradient time. The performance of the
      two platforms was tested using experimental and artificial data. It was found
      that using the proposed spreadsheets, fitting, prediction, and optimization can
      be performed easily and effectively under all conditions. Overall, the best
      performance is exhibited by the analytical and Nikitas-Pappa's methods, although
      the former cannot be used under all circumstances. 

PMID- 25869802
TI  - Global quantitative analysis of phosphorylation underlying phencyclidine
      signaling and sensorimotor gating in the prefrontal cortex.
AB  - Prepulse inhibition (PPI) is an example of sensorimotor gating and deficits in
      PPI have been demonstrated in schizophrenia patients. Phencyclidine (PCP)
      suppression of PPI in animals has been studied to elucidate the pathological
      elements of schizophrenia. However, the molecular mechanisms underlying PCP
      treatment or PPI in the brain are still poorly understood. In this study,
      quantitative phosphoproteomic analysis was performed on the prefrontal cortex
      from rats that were subjected to PPI after being systemically injected with PCP
      or saline. PCP downregulated phosphorylation events were significantly enriched
      in proteins associated with long-term potentiation (LTP). Importantly, this data
      set identifies functionally novel phosphorylation sites on known LTP-associated
      signaling molecules. In addition, mutagenesis of a significantly altered
      phosphorylation site on xCT (SLC7A11), the light chain of system xc-, the
      cystine/glutamate antiporter, suggests that PCP also regulates the activity of
      this protein. Finally, new insights were also derived on PPI signaling
      independent of PCP treatment. This is the first quantitative phosphorylation
      proteomic analysis providing new molecular insights into sensorimotor gating. 

PMID- 25869803
TI  - Neurofilament subunits are integral components of synapses and modulate
      neurotransmission and behavior in vivo.
AB  - Synaptic roles for neurofilament (NF) proteins have rarely been considered. Here,
      we establish all four NF subunits as integral resident proteins of synapses.
      Compared with the population in axons, NF subunits isolated from synapses have
      distinctive stoichiometry and phosphorylation state, and respond differently to
      perturbations in vivo. Completely eliminating NF proteins from brain by
      genetically deleting three subunits (alpha-internexin, NFH and NFL) markedly
      depresses hippocampal long-term potentiation induction without detectably
      altering synapse morphology. Deletion of NFM in mice, but not the deletion of any
      other NF subunit, amplifies dopamine D1-receptor-mediated motor responses to
      cocaine while redistributing postsynaptic D1-receptors from endosomes to plasma
      membrane, consistent with a specific modulatory role of NFM in D1-receptor
      recycling. These results identify a distinct pool of synaptic NF subunits and
      establish their key role in neurotransmission in vivo, suggesting potential novel
      influences of NF proteins in psychiatric as well as neurological states. 

PMID- 25869806
TI  - Identification of increased genetic risk scores for schizophrenia in treatment
      resistant patients.

PMID- 25869805
TI  - Targeting the schizophrenia genome: a fast track strategy from GWAS to clinic.
AB  - The Psychiatric Genomics Consortium-Schizophrenia Workgroup (PGC-SCZ) has
      recently published a genomewide association study (GWAS) identifying >100 genetic
      loci, encompassing a total of 341 protein-coding genes, attaining genomewide
      significance for susceptibility to schizophrenia. Given the extremely long time
      (12-15 years) and expense (>$1 billion) associated with the development of novel
      drug targets, repurposing of drugs with known and validated targets may be the
      most expeditious path toward deriving clinical utility from these GWAS findings.
      In the present study, we examined all genes within loci implicated by the PGC-SCZ
      GWAS against databases of targets of both approved and registered pharmaceutical
      compounds. We identified 20 potential schizophrenia susceptibility genes that
      encode proteins that are the targets of approved drugs. Of these, we prioritized
      genes/targets that are of clear neuropsychiatric interest and that are also sole
      members of the linkage disequilibrium block surrounding a PGC-SCZ GWAS hit. In
      addition to DRD2, 5 genes meet these criteria: CACNA1C, CACNB2, CACNA1I, GRIN2A
      and HCN1. An additional 20 genes coding for proteins that are the targets of
      drugs in registered clinical trials, but without approved indications, were also
      identified. Although considerable work is still required to fully explicate the
      biological implications of the PGC-SCZ GWAS results, pathways related to these
      known, druggable targets may represent a promising starting point. 

PMID- 25869807
TI  - NOMA-GAP/ARHGAP33 regulates synapse development and autistic-like behavior in the
      mouse.
AB  - Neuropsychiatric developmental disorders, such as autism spectrum disorders
      (ASDs) and schizophrenia, are typically characterized by alterations in social
      behavior and have been linked to aberrant dendritic spine and synapse
      development. Here we show, using genetically engineered mice, that the Cdc42
      GTPase-activating multiadaptor protein, NOMA-GAP, regulates autism-like social
      behavior in the mouse, as well as dendritic spine and synapse development.
      Surprisingly, we were unable to restore spine morphology or autism-associated
      social behavior in NOMA-GAP-deficient animals by Cre-mediated deletion of Cdc42
      alone. Spine morphology can be restored in vivo by re-expression of wild-type
      NOMA-GAP or a mutant of NOMA-GAP that lacks the RhoGAP domain, suggesting that
      other signaling functions are involved. Indeed, we show that NOMA-GAP directly
      interacts with several MAGUK (membrane-associated guanylate kinase) proteins, and
      that this modulates NOMA-GAP activity toward Cdc42. Moreover, we demonstrate that
      NOMA-GAP is a major regulator of PSD-95 in the neocortex. Loss of NOMA-GAP leads
      to strong upregulation of serine 295 phosphorylation of PSD-95 and moreover to
      its subcellular mislocalization. This is associated with marked loss of surface
      alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor and
      defective synaptic transmission, thereby providing a molecular basis for autism
      like social behavior in the absence of NOMA-GAP. 

PMID- 25869808
TI  - Valence-dependent influence of serotonin depletion on model-based choice
      strategy.
AB  - Human decision-making arises from both reflective and reflexive mechanisms, which
      underpin goal-directed and habitual behavioural control. Computationally, these
      two systems of behavioural control have been described by different learning
      algorithms, model-based and model-free learning, respectively. Here, we
      investigated the effect of diminished serotonin (5-hydroxytryptamine)
      neurotransmission using dietary tryptophan depletion (TD) in healthy volunteers
      on the performance of a two-stage decision-making task, which allows
      discrimination between model-free and model-based behavioural strategies. A novel
      version of the task was used, which not only examined choice balance for monetary
      reward but also for punishment (monetary loss). TD impaired goal-directed (model
      based) behaviour in the reward condition, but promoted it under punishment. This
      effect on appetitive and aversive goal-directed behaviour is likely mediated by
      alteration of the average reward representation produced by TD, which is
      consistent with previous studies. Overall, the major implication of this study is
      that serotonin differentially affects goal-directed learning as a function of
      affective valence. These findings are relevant for a further understanding of
      psychiatric disorders associated with breakdown of goal-directed behavioural
      control such as obsessive-compulsive disorders or addictions. 

PMID- 25869809
TI  - Determination of growth hormone releasing peptides metabolites in human urine
      after nasal administration of GHRP-1, GHRP-2, GHRP-6, Hexarelin, and Ipamorelin.
AB  - Growth hormone releasing peptides (GHRPs) stimulate secretion of endogenous
      growth hormone and are listed on the World Anti-Doping Agency (WADA) Prohibited
      List. To develop an effective method for GHRPs anti-doping control we have
      investigated metabolites of GHRP-1, GHRP-2, GHRP-6, Hexarelin, and Ipamorelin in
      urine after nasal administration. Each compound was administrated to one
      volunteer. Samples were collected for 2 days after administration, processed by
      solid-phase extraction on weak cation exchange cartridges and analyzed by means
      of nano-liquid chromatography - high resolution mass spectrometry. Six
      metabolites of GHRP-1 were identified. GHRP-1 in the parent form was not
      detected. GHRP-1 (2-4) free acid was detected in urine up to 27 h. GHRP-2, GHRP-2
      free acid and GHRP-2 (1-3) free acid were detected in urine up to 47 h after
      administration. GHRP-6 was mostly excreted unchanged and detected in urine 23 h
      after administration, its metabolites were detectable for 12 h only. Hexarelin
      and Ipamorelin metabolized intensively and were excreted as a set of parent
      compounds with metabolites. Hexarelin (1-3) free acid and Ipamorelin (1-4) free
      acid were detected in urine samples after complete withdrawal of parent
      substances. GHRPs and their most prominent metabolites were included into routine
      ultra-pressure liquid chromatography-tandem mass spectrometry procedure. The
      method was fully validated, calibration curves of targeted analytes were obtained
      and excretion curves of GHRPs and their metabolites were plotted. Our results
      confirm that the detection window after GHRPs administration depends on
      individual metabolism, drug preparation form and the way of administration.

PMID- 25869811
TI  - European palliative care guidelines: how well do they meet the needs of people
      with impaired cognition?
AB  - OBJECTIVE: Numbers of people dying with cognitive impairment (intellectual
      disability (ID), dementia or delirium) are increasing. We aimed to examine a
      range of European national palliative care guidelines to determine if, and how
      well, pain detection and management for people dying with impaired cognition are
      covered. METHODS: Questionnaires were sent to 14 country representatives of the
      European Pain and Impaired Cognition (PAIC) network who identified key national
      palliative care guidelines. Data was collected on guideline content: inclusion of
      advice on pain management, whether cognitively impaired populations were
      mentioned, assessment tools and management strategies recommended. Quality of
      guideline development was assessed with the Appraisal of Guidelines Research and
      Evaluation (AGREE) instrument. RESULTS: 11 countries identified palliative care
      guidelines, 10 of which mentioned pain management in general. Of these, seven
      mentioned cognitive impairment (3 dementia, 2 ID and 4 delirium). Half of
      guidelines recommended the use of pain tools for people with cognitive
      impairment; recommended tools were not all validated for the target populations.
      Guidelines from the UK, the Netherlands and Finland included most information on
      pain management and detection in impaired cognition. Guidelines from Iceland,
      Norway and Spain scored most highly on AGREE rating in terms of developmental
      quality. CONCLUSIONS: European national palliative care guidelines may not meet
      the needs of the growing population of people dying with cognitive impairment.
      New guidelines should consider suggesting the use of observational pain tools for
      people with cognitive impairment. Better recognition of their needs in palliative
      care guidelines may drive improvements in care.

PMID- 25869804
TI  - GWAS for executive function and processing speed suggests involvement of the
      CADM2 gene.
AB  - To identify common variants contributing to normal variation in two specific
      domains of cognitive functioning, we conducted a genome-wide association study
      (GWAS) of executive functioning and information processing speed in non-demented
      older adults from the CHARGE (Cohorts for Heart and Aging Research in Genomic
      Epidemiology) consortium. Neuropsychological testing was available for 5429
      32,070 subjects of European ancestry aged 45 years or older, free of dementia and
      clinical stroke at the time of cognitive testing from 20 cohorts in the discovery
      phase. We analyzed performance on the Trail Making Test parts A and B, the Letter
      Digit Substitution Test (LDST), the Digit Symbol Substitution Task (DSST),
      semantic and phonemic fluency tests, and the Stroop Color and Word Test.
      Replication was sought in 1311-21860 subjects from 20 independent cohorts. A
      significant association was observed in the discovery cohorts for the single
      nucleotide polymorphism (SNP) rs17518584 (discovery P-value=3.12 * 10(-8)) and in
      the joint discovery and replication meta-analysis (P-value=3.28 * 10(-9) after
      adjustment for age, gender and education) in an intron of the gene cell adhesion
      molecule 2 (CADM2) for performance on the LDST/DSST. Rs17518584 is located about
      170 kb upstream of the transcription start site of the major transcript for the
      CADM2 gene, but is within an intron of a variant transcript that includes an
      alternative first exon. The variant is associated with expression of CADM2 in the
      cingulate cortex (P-value=4 * 10(-4)). The protein encoded by CADM2 is involved
      in glutamate signaling (P-value=7.22 * 10(-15)), gamma-aminobutyric acid (GABA)
      transport (P-value=1.36 * 10(-11)) and neuron cell-cell adhesion (P-value=1.48 *
      10(-13)). Our findings suggest that genetic variation in the CADM2 gene is
      associated with individual differences in information processing speed.

PMID- 25869812
TI  - The Mismatch Between Children's Health Needs and School Resources.
AB  - There are increasing numbers of children with special health care needs (CSHCN)
      who require various levels of care each school day. The purpose of this study was
      to examine the role of public schools in supporting CSHCN through in-depth key
      informant interviews. For this qualitative study, the authors interviewed 17 key
      informants to identify key themes, provide recommendations, and generate
      hypotheses for further statewide survey of school nurse services. Key informants
      identified successful strategies and challenges that public schools face in
      meeting the needs of all CSHCN. Although schools are well intentioned, there is
      wide variation in the ability of schools to meet the needs of CSHCN. Increased
      funding, monitoring of school health services, integration of services, and
      interagency collaboration are strategies that could improve the delivery of
      health services to CSHCN in schools. 

PMID- 25869810
TI  - Deletion of adenosine A2A receptors from astrocytes disrupts glutamate
      homeostasis leading to psychomotor and cognitive impairment: relevance to
      schizophrenia.
AB  - BACKGROUND: Adenosine A2A receptors (A2AR) modulate dopamine and glutamate
      signaling and thereby may influence some of the psychomotor and cognitive
      processes associated with schizophrenia. Because astroglial A2AR regulate the
      availability of glutamate, we hypothesized that they might play an unprecedented
      role in some of the processes leading to the development of schizophrenia, which
      we investigated using a mouse line with a selective deletion of A2AR in
      astrocytes (Gfa2-A2AR knockout [KO] mice]. METHODS: We examined Gfa2-A2AR KO mice
      for behaviors thought to recapitulate some features of schizophrenia, namely
      enhanced MK-801 psychomotor response (positive symptoms) and decreased working
      memory (cognitive symptoms). In addition, we probed for neurochemical alterations
      in the glutamatergic circuitry, evaluating glutamate uptake and release and the
      levels of key proteins defining glutamatergic signaling (glutamate transporter-I
      [GLT-I], N-methyl-D-aspartate receptors [NMDA-R] and alpha-3-hydroxy-5-methyl-4
      isoxazolepropionic acid receptors [AMPA-R]) to provide a mechanistic
      understanding of the phenotype encountered. RESULTS: We show that Gfa2-A2AR KO
      mice exhibited enhanced MK-801 psychomotor response and decreased working memory;
      this was accompanied by a disruption of glutamate homeostasis characterized by
      aberrant GLT-I activity, increased presynaptic glutamate release, NMDA-R 2B
      subunit upregulation, and increased internalization of AMPA-R. Accordingly,
      selective GLT-I inhibition or blockade of GluR1/2 endocytosis prevented the
      psychomotor and cognitive phenotypes in Gfa2-A2AR KO mice, namely in the nucleus
      accumbens. CONCLUSIONS: These results show that the dysfunction of astrocytic
      A2AR, by controlling GLT-I activity, triggers an astrocyte-to-neuron wave of
      communication resulting in disrupted glutamate homeostasis, thought to underlie
      several endophenotypes relevant to schizophrenia.

PMID- 25869813
TI  - Stationary-phase induction of vvpS expression by three transcription factors:
      repression by LeuO and activation by SmcR and CRP.
AB  - An exoprotease of Vibrio vulnificus, VvpS, exhibits an autolytic function during
      the stationary phase. To understand how vvpS expression is controlled, the
      regulators involved in vvpS transcription and their regulatory mechanisms were
      investigated. LeuO was isolated in a ligand-fishing experiment, and experiments
      using a leuO-deletion mutant revealed that LeuO represses vvpS transcription.
      LeuO bound the extended region including LeuO-binding site (LBS)-I and LBS-II.
      Further screening of additional regulators revealed that SmcR and cyclic
      adenosine monophosphate-receptor protein (CRP) play activating roles in vvpS
      transcription. SmcR and CRP bound the regions overlapping LBS-I and -II,
      respectively. In addition, the LeuO occupancy of LBS-I and LBS-II was
      competitively exchanged by SmcR and CRP, respectively. To examine the mechanism
      of stationary-phase induction of vvpS expression, in vivo levels of three
      transcription factors were monitored. Cellular level of LeuO was maximal at
      exponential phase, while those of SmcR and CRP were maximal at stationary phase
      and relatively constant after the early-exponential phase, respectively. Thus,
      vvpS transcription was not induced during the exponential phase by high cellular
      content of LeuO. When entering the stationary phase, however, LeuO content was
      significantly reduced and repression by LeuO was relieved through simultaneous
      binding of SmcR and CRP to LBS-I and -II, respectively. 

PMID- 25869814
TI  - Evolution from laparoscopic to robotic nephron sparing surgery: a high-volume
      laparoscopic center experience on achieving 'trifecta' outcomes.
AB  - OBJECTIVE: To evaluate the transition from laparoscopic (LPN) to robotic partial
      nephrectomy (RPN) in our institution using 'trifecta' outcomes as surrogate
      marker of efficacy. PATIENTS AND METHODS: We identified 347 patients (LPN = 303,
      RPN = 44) in our prospectively maintained PN database between 2000 and 2014. The
      patients were chronologically divided into G1-first 151 LPN cases, G2-subsequent
      152 LPN cases and G3-all RPN patients. Trifecta outcomes were defined as warm
      ischemia time (WIT) <=25 min, no positive surgical margin (PSM) and complications
      <=Clavien 2. Multivariable logistic model was used to analyze the predictors of
      the trifecta outcomes. RESULTS: The tumor complexity significantly increased from
      G1 to G3. We achieved lower WIT and less high-grade complication (Clavien >= 3)
      from G1 to G2, and the trend continued even with transition to RPN. PSM was
      consistently low throughout the transition. Renal functional outcomes always
      showed a significant positive trend, and with RPN, we achieved improved recovery
      of renal function (44 vs 57 vs 82 %, p < 0.05). The overall 'trifecta' rates
      increased significantly from G1 to G2 and reached 81.8 % in RPN (48 vs 75.6 vs 81
      %, p < 0.01). Multivariate analysis has shown that the use of robot has
      significant effect on achieving overall trifecta. The limitations of the study
      are being retrospective and non-randomized, and the trifecta definitions were not
      externally validated. CONCLUSIONS: Our transition to RPN was essentially a
      continuation of our previous LPN experience as we continue to achieve higher
      'trifecta' rates inspite of increasing tumor complexity.

PMID- 25869815
TI  - Naftopidil versus flopropione as medical expulsive therapy for distal ureteral
      stones: results of a randomized, multicenter, double-blind, controlled trial.
AB  - PURPOSE: A multicenter, double-blind, randomized, controlled trial was conducted
      to determine the efficacy of naftopidil as medical expulsive therapy (MET) for
      patients with distal ureteral stones. METHODS: Ninety-two patients presenting
      with a single distal ureteral stone <=10 mm were randomly assigned to receive
      either naftopidil (75 mg of naftopidil once in the morning and placebo twice a
      day) or flopropione (80 mg three times a day). The primary end point was time to
      stone expulsion calculated by the Kaplan-Meier method. Secondary end points were
      the percentages of patients who required analgesics, hospital admission, and
      surgery, the number of working days lost to the disease, and treatment safety.
      RESULTS: Overall, three patients were excluded from the final analysis. No
      significant differences were noted in age, stone size, and stone side between the
      treatment arms. The median time to stone expulsion was 8 days [95 % confidence
      interval (CI), 3-16] for the naftopidil group, and this was significantly less
      than the 18 days (95 % CI, 11 to not reached) for the flopropione group (p =
      0.03). On multivariate Cox regression analysis, the hazard of expulsion was 1.8
      fold higher for the naftopidil group than for the flopropione group after
      adjustment for age, sex, stone side, and stone size. No significant differences
      were noted in the secondary end points. CONCLUSIONS: The administration of
      naftopidil significantly improved time to stone expulsion in patients with distal
      ureteral stones <=10 mm. We believe that this is the first multicenter, double
      blind, randomized, controlled trial demonstrating the efficacy of naftopidil for
      MET.

PMID- 25869816
TI  - Are some health professionals more cognizant of clinical governance development
      concepts than others? Findings from a New Zealand study.
AB  - BACKGROUND: Clinical governance has been promoted in recent years as core to
      improving patient safety. Effective clinical governance requires partnerships
      between 'management' and health professionals as well as equal involvement of all
      professional groups. Professionals must also be willing to engage in clinical
      governance activities such as working to improve care systems and patient safety.
      There is limited research into the relative understanding of core clinical
      governance concepts amongst different professional groups or the extent to which
      professionals are prepared to take up opportunities to 'change the system'.
      METHODS: A 2012 national survey study of health professionals employed in New
      Zealand health boards sought to probe understanding of and commitment to clinical
      governance following introduction of a 2009 policy. RESULTS: Respondent data
      showed only limited policy implementation had occurred. Regression analyses
      revealed statistically significant differences in perceptions of knowledge of
      clinical governance concepts and structures by gender, age, experience and
      profession, as well as in seeking opportunities to change the system.
      CONCLUSIONS: These findings have implications for policy makers in terms of
      ensuring that clinical governance implementation provides equal opportunity for
      engendering involvement of different health professionals.

PMID- 25869817
TI  - The role of phagocytosis, oxidative burst and neutrophil extracellular traps in
      the interaction between neutrophils and the periodontal pathogen Porphyromonas
      gingivalis.
AB  - Neutrophils are regarded as the sentinel cells of innate immunity and are found
      in abundance within the gingival crevice. Discovery of neutrophil extracellular
      traps (NETs) within the gingival pockets prompted us to probe the nature of the
      interactions of neutrophils with the prominent periopathogen Porphyromonas
      gingivalis. Some of the noted virulence factors of this Gram-negative anaerobe
      are gingipains: arginine gingipains (RgpA/B) and lysine gingipain (Kgp). The aim
      of this study was to evaluate the role of gingipains in phagocytosis, formation
      of reactive oxygen species, NETs and CXCL8 modulation by using wild-type strains
      and isogenic gingipain mutants. Confocal imaging showed that gingipain mutants
      K1A (Kgp) and E8 (RgpA/B) induced extracellular traps in neutrophils, whereas
      ATCC33277 and W50 were phagocytosed. The viability of both ATCC33277 and W50
      dwindled as the result of phagocytosis and could be salvaged by cytochalasin D,
      and the bacteria released high levels of lipopolysaccharide in the culture
      supernatant. Porphyromonas gingivalis induced reactive oxygen species and CXCL8
      with the most prominent effect being that of the wild-type strain ATCC33277,
      whereas the other wild-type strain W50 was less effective. Quantitative real-time
      polymerase chain reaction revealed a significant CXCL8 expression by E8. All the
      tested P. gingivalis strains increased cytosolic free calcium. In conclusion,
      phagocytosis is the primary neutrophil response to P. gingivalis, although NETs
      could play an accessory role in infection control. Although gingipains do not
      seem to directly regulate phagocytosis, NETs or oxidative burst in neutrophils,
      their proteolytic properties could modulate the subsequent outcomes such as
      nutrition acquisition and survival by the bacteria.

PMID- 25869818
TI  - The relevance of work-related learning for vulnerable groups. Dutch case study of
      a Health Impact Assessment with equity focus.
AB  - INTRODUCTION: Learning is essential for sustainable employability. However,
      various factors make work-related learning more difficult for certain groups of
      workers, who are consequently at a disadvantage in the labour market. In the long
      term, that in turn can have adverse health implications and can make those groups
      vulnerable. With a view to encouraging workers to continue learning, the
      Netherlands has a policy on work-related learning, which forms part of the
      'Vitality Package'. AIM: A Health Impact Assessment with equity focus (HIAef) was
      undertaken to determine whether the policy on work-related learning affected
      certain groups of workers and their health in different ways, and whether the
      differences were avoidable. METHODS: The HIAef method involved the standard
      phases: screening, scoping, appraisal and recommendations. Equity was the core
      principle in this method. Data were collected by means of both literature
      searches (e.g., Scopus, Medline) and interviews with experts and stakeholders
      (e.g., expertise regarding work, training and/or health). RESULTS: The HIAef
      identified the following groups as potentially vulnerable in the field of work
      related learning: the chronically sick, older people, less educated people, flexi
      workers/the self-employed and lay carers (e.g., thresholds to learning).
      Published literature indicates that work-related learning may have a positive
      influence on health through (work-related) factors such as pay, employability,
      longer employment rate and training-participation. According to experts and
      stakeholders, work-related learning policy could be adapted to take more account
      of vulnerable groups through alignment with their particular needs, such as early
      support, informal learning and e-learning. CONCLUSION: With a view to reducing
      avoidable inequalities in work-related learning, it is recommended that early,
      low-threshold, accessible opportunities are made available to identified
      vulnerable groups. Making such opportunities available may have a positive effect
      on (continued) participation in the labour market and thus on the health of the
      relevant groups.

PMID- 25869819
TI  - The relationship between patient functional status and environmental
      contamination by Clostridium difficile: a pilot study.
AB  - INTRODUCTION: Limited data exist on patient factors related to environmental
      contamination with Clostridium difficile. METHODS: We evaluated the association
      between the functional status of patients with C. difficile infection (CDI) and
      environmental contamination with C. difficile. RESULTS: Contamination of patient
      rooms was frequent and higher functional status was associated with contaminated
      surfaces remote from the bed. All but one environmental isolates matched the
      corresponding patient's stool isolate for the seven patients tested. CONCLUSION:
      Functional status is a factor that influences environmental contamination with C.
      difficile. Future studies should evaluate strategies to reduce contamination in
      CDI patient rooms, taking into account the patient's functional status.

PMID- 25869820
TI  - Twenty-eight cases of Mycobacterium marinum infection: retrospective case series
      and literature review.
AB  - PURPOSE: Invasive Mycobacterium marinum disease (tenosynovitis and osteomyelitis)
      may be an increasingly common manifestation of M. marinum infection that presents
      unique diagnostic and therapeutic challenges. We conducted a retrospective case
      series and literature review of M. marinum infection to better understand the
      clinical spectrum of invasive versus cutaneous disease. METHODS: We reviewed
      electronic medical records for all M. marinum infections at Duke University
      Medical Center from January 1, 1996 to April 30, 2014. Published case series of
      M. marinum infection since 1990 reporting >5 cases were systematically
      ascertained and reviewed. RESULTS: Twenty-eight cases of M. marinum infection
      were identified from our institution. Twenty cases (87 %) involved aquatic
      exposure, and 26 (93 %) involved finger and/or hand lesions. Median time to
      diagnosis was 3.5 months. Nineteen (68 %) cases had invasive infection, and 9 (32
      %) were cutaneous; invasive infection was more common with older age.
      Granulomatous inflammation and acid-fast bacilli were noted on pathologic
      examination in 11 (58 %) and 3 (16 %) cases, respectively. Primarily monotherapy
      was used in 2 (12 %) cases, dual therapy in 8 (47 %) cases, and three-drug
      therapy in 7 (41 %) cases; three-drug therapy was more common with invasive
      infection. Median duration of treatment was 5 months. Adjunctive surgery was
      performed for 18 (95 %) cases of invasive infection and 4 (44 %) of cutaneous
      infection. Twenty-one (75 %) cases improved, while 7 (25 %) were lost to follow
      up. CONCLUSIONS: Distinguishing between invasive and cutaneous M. marinum
      infection may have important consequences in terms of antibiotic choice and need
      for adjunctive surgery.

PMID- 25869821
TI  - Rational application of adenosine deaminase activity in cerebrospinal fluid for
      the diagnosis of tuberculous meningitis.
AB  - PURPOSE: Tuberculous meningitis (TBM) is one of the most serious and difficult to
      diagnose manifestations of TB. An ADA value >9.5 IU/L has great sensitivity and
      specificity. However, all available studies have been conducted in areas of high
      endemicity, so we sought to determine the accuracy of ADA in a low endemicity
      area. METHODS: This retrospective study included 190 patients (105 men) who had
      ADA tested in CSF for some reason. Patients were classified as probable/certain
      TBM or non-TBM based on clinical and Thwaite's criteria. Optimal ADA cutoff was
      established by ROC curves and a predictive algorithm based on ADA and other CSF
      biochemical parameters was generated. RESULTS: Eleven patients were classified as
      probable/certain TBM. In a low endemicity area, the best ADA cutoff was 11.5 IU/L
      with 91 % sensitivity and 77.7 % specificity. We also developed a predictive
      algorithm based on the combination of ADA (>11.5 IU/L), glucose (<65 mg/dL) and
      leukocytes (>=13.5 cell/mm(3)) with increased accuracy (Se: 91 % Sp: 88 %).
      CONCLUSIONS: Optimal ADA cutoff value in areas of low TB endemicity is higher
      than previously reported. Our algorithm is more accurate than ADA activity alone
      with better sensitivity and specificity than previously reported algorithms.

PMID- 25869822
TI  - Prevalence of intestinal parasite infections and associated clinical symptoms
      among patients with end-stage renal disease undergoing hemodialysis.
AB  - PURPOSE: Intestinal parasitic infections (IPIs) can result in high morbidity and
      mortality, particularly in immunocompromised patients. Infectious diseases are
      among the main causes of death in end-stage renal disease (ESRD) patients due to
      their impaired immune systems. The aim of this study was to determine the
      prevalence IPIs and their associated symptoms in ESRD patients. METHODS: In this
      case-control study, the fecal samples of 78 ESRD patients undergoing hemodialysis
      and 140 controls without any kidney problems were analyzed for intestinal
      parasites using direct-smear, formol-ether and modified Ziehl-Neelsen staining
      techniques. RESULTS: The difference in the prevalence of IPIs between ESRD
      patients (30.7 %) and the control group (10.7 %) was significant (OR = 3.7; 95 %
      CI = 1.8-7.61; P < 0.001). Blastocystis (14.1 %) and Cryptosporidium spp.(11.5 %)
      were the most common IPIs detected in ESRD patients, and the presence of
      Cryptosporidium spp. was significantly associated with diarrhea in ESRD patients
      (OR = 16; 95 % CI = 1.54-166.05; P < 0.05). Leukocytosis, diarrhea, weight loss,
      nausea/vomiting and bloating were also significantly higher in the hemodialysis
      group when compared with the control group. CONCLUSION: The current study
      revealed a high prevalence of intestinal parasites and related clinical symptoms
      in ESRD patients undergoing hemodialysis. Since hemodialysis patients are
      immunocompromised and intestinal parasites can cause serious clinical
      complications, we suggest that stool examination for intestinal parasites, with
      an emphasis on detection of Cryptosporidium spp. and Blastocystis, should be
      incorporated into the routine clinical care for these patients. Measures for
      preventing the acquisition of IPIs are also recommended.

PMID- 25869823
TI  - SWI/SNF recruitment to a DNA double-strand break by the NuA4 and Gcn5 histone
      acetyltransferases.
AB  - The DNA damage response to double-strand breaks (DSBs) is critical for cellular
      viability. Recent work has shown that a host of chromatin regulators are
      recruited to a DSB, and that they are important for the DNA damage response.
      However, the functional relationships between different chromatin regulators at
      DSBs remain unclear. Here we describe a conserved functional interaction among
      the chromatin remodeling enzyme, SWI/SNF, the NuA4 and Gcn5 histone
      acetyltransferases, and phosphorylation of histone H2A.X (gammaH2AX).
      Specifically, we find that the NuA4 and Gcn5 enzymes are both required for the
      robust recruitment of SWI/SNF to a DSB, which in turn promotes the
      phosphorylation of H2A.X. 

PMID- 25869824
TI  - Topoisomerase I deficiency causes RNA polymerase II accumulation and increases
      AID abundance in immunoglobulin variable genes.
AB  - Activation-induced deaminase (AID) is a DNA cytosine deaminase that diversifies
      immunoglobulin genes in B cells. Recent work has shown that RNA polymerase II
      (Pol II) accumulation correlates with AID recruitment. However, a direct link
      between Pol II and AID abundance has not been tested. We used the DT40 B-cell
      line to manipulate levels of Pol II by decreasing topoisomerase I (Top1), which
      relaxes DNA supercoiling in front of the transcription complex. Top1 was
      decreased by stable transfection of a short hairpin RNA against Top1, which
      produced an accumulation of Pol II in transcribed genes, compared to cells
      transfected with sh-control RNA. The increased Pol II density enhanced AID
      recruitment to variable genes in the lambda light chain locus, and resulted in
      higher levels of somatic hypermutation and gene conversion. It has been proposed
      by another lab that AID itself might directly suppress Top1 to increase somatic
      hypermutation. However, we found that in both AID(+/+) and AID(-/-) B cells from
      DT40 and mice, Top1 protein levels were identical, indicating that the presence
      or absence of AID did not decrease Top1 expression. Rather, our results suggest
      that the mechanism for increased diversity when Top1 is reduced is that Pol II
      accumulates and recruits AID to variable genes. 

PMID- 25869825
TI  - Can the effect of adhesion barriers and/or intravesical balloon inflation improve
      bladder autoaugmentation outcomes in a rabbit model?
AB  - INTRODUCTION: Bladder augmentation is used for the treatment of bladder
      dysfunction in order to minimize intravesical pressure and increase bladder
      capacity. However, less-invasive procedures, such as autoaugmentation, have been
      proposed due to several complications that have occurred using bowel and gastric
      segments. The technique of autoaugmentation involves wide excision of the
      detrusor by leaving the bladder mucosa intact and has shown increased bladder
      capacity and compliance. An additional step to keep the achieved surface area of
      this non-contractible bladder segment and, thus, bladder capacity, was reported
      by using an intravesical balloon to prevent shrinkage of the surgically achieved
      diverticulum during autoaugmentation. On the other hand, adhesion barriers (AB)
      with absorbable hydrogel, which can spare tissue and organ plans, are used to
      prevent postsurgical adhesions. The efficacy of sprayable AB has been
      demonstrated in animal models and it is now mostly used in laparoscopic
      surgeries. OBJECTIVE: The present study aimed to compare the efficacy of AB
      and/or intravesical balloon insertion, which might potentially improve the
      urodynamic and histopathological outcomes of autoaugmentation in a rabbit model.
      METHODS: A total of 25 New Zealand rabbits were included in the study. Following
      the surgical reduction to form a low-capacity bladder model (35-40% of the
      initial volume), standard detrusorotomy was performed in all groups except the
      sham group. Group 2 had only autoaugmentation as the control group. The bladders
      in Group 3 were supported with an intravesical balloon. An Adhesion Barrier
      System (CUI Tissue Expander) was used for all bladders in Group 4, without
      balloon inflation. In Group 5, both intravesical balloon inflation and adhesion
      barrier application were performed following autoaugmentation. Urodynamic
      evaluations were performed at day 0 before reduction, day 0 after reduction, and
      the 90th postoperative day. Capacity and compliance measurements were noted.
      Bladders were histopathologically evaluated. Expression of CD31 (microvessel
      density) and fibrosis were noted. RESULTS: Autoaugmentation does not result in a
      reliable increase in bladder capacity and compliance when compared to a sham
      group. Urodynamic measurements were similar in balloon-inflated groups (Group 3
      and Group 5), showing a statistically significant improvement. Sprayable AB
      system alone revealed a slight, but not statistically significant, increase
      (Table). No significant differences between all five groups were detected
      regarding microvessel density (CD31 expression) and fibrosis. DISCUSSION: In the
      present study, the intravesical balloon application (IVBA) efficiency was
      investigated alone and in combination with AB. The main basis of this study were
      the previous findings, which demonstrated prevention or decrease in the
      contraction of diverticula by IVBA. The role of AB alone or within a combination
      was also evaluated. Adhesion barriers are mostly used in laparoscopic gynecologic
      and colorectal operations. They decrease the postoperative adhesions by forming a
      physical barrier. In the present study, it was thought that AB might reduce
      postoperative adhesions and enhance the outcome of autoaugmentation. One of the
      most important outcomes was the inconsistency of fibrosis density with final
      bladder capacity and compliance values; this finding did not support the role of
      fibrosis prevention with IVBA. The present study had some limitations: the
      partial cystectomy method, which was used to form a low-compliance bladder, is a
      different clinical condition to neurogenic bladder, and a rectal catheter was not
      used during urodynamic evaluation. General anesthesia and muscle relaxant were
      performed during urodynamy and abdominal contractions were not seen. CONCLUSION:
      Bladder autoaugmentation in a rabbit model, followed by intravesical balloon
      inflation offers improvement in bladder capacity and compliance. The use of
      sprayable adhesion barrier hydrogel technology may facilitate tissue healing and
      result in it being easier to maintain the success achieved by surgery when only
      supported with an intravesical balloon.

PMID- 25869826
TI  - Delayed surgical repair of posttraumatic posterior urethral distraction defects
      in children and adolescents: long-term results.
AB  - INTRODUCTION: Various surgical techniques have been proposed to treat pelvic
      fracture urethral distraction defects (PFUDDs) in children (Figure): primary
      alignment of the acute transected urethra, substitution procedures and delayed
      anastomosis urethroplasties (DAU) by perineal, elaborated perineal, transpubic or
      perineo-abdominal/partial transpubic access. However, long-term follow-up of
      surgical correction for PFUDDS with DAU is infrequently reported in the
      literature. PURPOSE: Long-term efficacy of DAU in children and adolescents with
      PFUDDs was evaluated. Other surgical methods used to accomplish tension-free DAU
      were also described. MATERIAL AND METHODS: We reviewed records of 49 male
      children aged 3.5-17.5 years (median 9.6) with PFUDDS who underwent DAU from 1980
      to 2006. Median PFUDDs length was 3 cm (range 2-6). Six patients had prior failed
      treatments: anastomotic urethroplasties (5) and internal urethrotomy (1).
      Surgical access was transperineal in 28 cases and perineal/partial pubectomy in
      21. Urethral rerouting was performed in 8 cases. Median follow-up was 6.5 years
      (range 5-22). RESULTS: On review median PFUDDS length in patients treated with
      primary cystostomy was 3 cm compared to those initially managed with urethral
      alignment (4 cm). Five patients treated with perineal DAU developed recurrent
      strictures at the anastomosis site, successfully managed with additional
      perineal/partial pubectomy anastomosis (4 cases) and internal urethrotomy (1).
      Primary and overall success rate was 89, 7% and 100%, respectively. Urinary
      incontinence occurred in 9 cases. Two had overflow incontinence and performed
      self-catheterization; 1 developed sphincter incontinence and required AUS
      placement, while 4 of 6 cases with mild stress incontinence achieved dryness at
      pubertal age. Retrospectively, associated bladder neck lesions at trauma time
      were noted in 5 patients. Three patients with erectile dysfunction before DAU
      remained impotent. DISCUSSION: In children, several factors make management of
      PFUDDs more difficult than in adults: 1) restricted surgical access to reach a
      high lying proximal urethral end, 2) long distraction defects, 3) simultaneous
      bladder neck and membranous urethral lesions and 4) small urethral caliber. In
      our experience and that of others (Turner Warwick, 1989 and Ranjan, 2012),
      radiographic and endoscopic findings provide information on stricture features;
      however, the final choice of surgical exposure to restore urethral continuity is
      made at operative time based on PFUDD complexity. Perineal exposure usually
      allows performing DAU in 2 cm long PFUDDs. Ten percent of our patients treated
      with perineal DAU developed recurrent strictures attributed to inappropriate
      access selection or unrecognized PFUDD complexity. Failures were treated
      endoscopically (1) and by perineal/partial pubectomy anastomotic urethroplasty
      (4) with 100% final success. We used perineal/partial pubectomy DAU in 43% of the
      cases to excise pelvic scarring and bridge long urethral gaps, with urethral
      rerouting in 8 cases. Success rate of initial perineal and perineal/partial
      pubectomy anastomotic procedures was 82% and 100%, respectively. Koraitim (1997),
      Orabi (2008) and Ranjan (2012) reported excellent outcomes in children with
      either transperineal or transpubic anastomotic repair, as opposed to poor results
      in those undergoing substitution urethroplaties. Most reports rarely evaluate
      urinary incontinence after successful DAU. At the end of follow-up only 2 of our
      9 initial incontinent cases remain with acceptable stress incontinence.
      Retrospectively, in 5 cases the original trauma comprised the bladder neck and
      the membranous sphincter mechanism. In our series erectile dysfunction after
      trauma did not change after DAU except in 1 patient who regained potency 1 year
      after repair. STUDY LIMITATIONS: All patients were referred after initial
      treatment was done elsewhere, thus they may represent the most severe PFUDDs
      cases. Additionally, erection dysfunction was not investigated in the kind of
      detail required due to patients' age. CONCLUSIONS: DAU has durable success rate
      for PFUDDs treatment in children with a healthy bulbar urethra. In childhood,
      additional surgical steps are frequently needed to achieve direct anastomotic
      repair.

PMID- 25869827
TI  - Client attachment security predicts alliance in a randomized controlled trial of
      two psychotherapies for bulimia nervosa.
AB  - OBJECTIVE: This study investigated the relation between clients' attachment
      patterns and the therapeutic alliance in two psychotherapies for bulimia nervosa.
      METHOD: Data derive from a randomized clinical trial comparing cognitive
      behavioral therapy (CBT) and psychoanalytic psychotherapy (PPT) for bulimia
      nervosa. Client attachment patterns were assessed with the Adult Attachment
      Interview. Independent raters scored audiotapes of early, middle, and late
      therapy sessions for 68 clients (175 sessions) using the Vanderbilt Therapeutic
      Alliance Scale. RESULTS: Client attachment security was found to be a significant
      (p = .007) predictor of alliance levels at the three measured time points, with
      clients higher on attachment security developing stronger alliances with their
      therapists in both treatments as compared to clients higher on attachment
      insecurity. No evidence was found to support a hypothesized interaction whereby
      dismissing clients would develop weaker alliances in PPT and preoccupied clients
      would develop weaker alliances in CBT. CONCLUSIONS: As the first study to examine
      client attachment and therapeutic alliance using observer-based instruments, this
      study supports the theoretical assumption that clients with secure attachment
      patterns are likely to develop stronger alliances with their therapist across
      different treatment settings.

PMID- 25869829
TI  - Welcome to Forensic science, medicine, and pathology.

PMID- 25869828
TI  - Longitudinal analysis of DNA methylation associated with birth weight and
      gestational age.
AB  - Gestational age (GA) and birth weight have been implicated in the determination
      of long-term health. It has been hypothesized that changes in DNA methylation may
      mediate these long-term effects. We obtained DNA methylation profiles from cord
      blood and peripheral blood at ages 7 and 17 in the same children from the Avon
      Longitudinal Study of Parents and Children. Repeated-measures data were used to
      investigate changes in birth-related methylation during childhood and
      adolescence. Ten developmental phenotypes (e.g. height) were analysed to identify
      possible mediation of health effects by DNA methylation. In cord blood,
      methylation at 224 CpG sites was found to be associated with GA and 23 CpG sites
      with birth weight. Methylation changed in the majority of these sites over time,
      but neither birth characteristic was strongly associated with methylation at age
      7 or 17 (using a conservative correction for multiple testing of P < 1.03 * 10(
      7)), suggesting resolution of differential methylation by early childhood.
      Associations were observed between birth weight-associated CpG sites and
      phenotypic characteristics in childhood. One strong association involved birth
      weight, methylation of a CpG site proximal to the NFIX locus and bone mineral
      density at age 17. Analysis of serial methylation from birth to adolescence
      provided evidence for a lack of persistence of methylation differences beyond
      early childhood. Sites associated with birth weight were linked to developmental
      genes and have methylation levels which are associated with developmental
      phenotypes. Replication and interrogation of causal relationships are needed to
      substantiate whether methylation differences at birth influence the association
      between birth weight and development. 

PMID- 25869830
TI  - The tsunami : An environmental mass disaster.

PMID- 25869831
TI  - Controversies in pediatric forensic pathology.
AB  - Pediatric forensic pathology is an emerging medical subspecialty that spans the
      area between pediatric and forensic pathology. Advances in both of these fields
      have increased the sophistication of diagnoses, with overlap of disorders that
      might present to either the pediatric or forensic pathologist, adding further
      layers of complexity. Not surprisingly, therefore, there are important ethical
      and medical controversies in pediatric forensic pathology that merit careful
      consideration and attention. 

PMID- 25869832
TI  - The pathology of whiplash maculopathy and retinopathy : Illustrated observations
      derived from a fatal roller-coaster accident.
AB  - We present a single case report of a 20-year-old female who died following a
      severe whiplash head and neck injury sustained during a roller-coaster incident.
      We present the pathology of her eyes, which we believe to be the first
      pathological illustration of whiplash maculopathy and retinopathy to be reported
      within the medical literature. This article presents the macroscopic and
      microscopic pathology identified in this case and discusses the possible
      causation of the findings. 

PMID- 25869833
TI  - Individual differences in the kinetics of alcohol absorption and elimination : A
      human study.
AB  - The individual differences in alcohol pharmacokinetics were studied using the one
      compartment model with first-order absorption and zero-order elimination kinetics
      in humans. The blood alcohol concentrations (BACs) were simulated by obtained
      parameters, absorption rate constant (ka), and climination rate constant (beta).
      The 81 healthy young Japanese volunteers, who had been divided into those without
      alcohol-induced facial flushing (nonflushers) and those with facial flushing
      (flushers) according to alcohol patch test results and a questionnaire
      beforehand, ingested 0.50 g/kg ethanol within 1 minute. Breath alcohol
      concentrations (BrACs) were measured during absorption and during the elimination
      period. BACs were obtained based on BrACs. Fifteen percent of subjects exhibited
      low BAC profile (below 0.4 mg/mL) (first-pass effect [FPE] group), although the
      majority showed normal BAC profile (normal group). The ka was approximately 5 to
      8 (h(-1)) in the normal group without significant difference between nonflushers
      and flushers, whereas that in the FPE group was significantly smaller than in the
      normal group. For the normal group, peak BACs were well simulated by the one
      compartment model with first-order absorption and zero-order elimination
      kinetics. A considerable portion of subjects exhibited FPE. Absorption of alcohol
      from the intestine plays an important role in alcohol pharmacokinetics in humans.

PMID- 25869834
TI  - An approach to the evaluation of fatal hypothermia.
AB  - The diagnosis of death caused by hypothermia can often only be made by exclusion.
      In this article, we discuss the significance of rectal temperature determination
      at the death scene for establishing the diagnosis of fatal hypothermia. Six cases
      of fatal hypothermia subjected to medico-legal autopsy at the Institute of Legal
      Medicine, Hamburg, Germany, were reviewed. Findings at external examination,
      autopsy findings with special regard to characteristics hypothermia-related
      changes, histological findings, and toxicology results were analyzed. In all
      cases investigated, a discrepancy between a low rectal temperature and other
      parameters for estimation of the time since death such as still displaceable
      postmortem lividity and electrical excitability of skeletal muscles was present,
      leading to the prompt suspicion of fatal hypothermia at the medico-legal death
      scene investigation. An early death scene investigation by a forensic specialist
      is of striking importance for establishing the correct diagnosis, because this
      discrepancy can only be observed in the early postmortem interval. 

PMID- 25869835
TI  - Autopsy problems associated with postmortem ant activity.
AB  - Postmortem damage to skin caused by ants may result in lesions that resemble
      inflicted or noninflicted antemortem injuries. In addition, if this superficial
      skin loss is located in a dependent area, there may be considerable passive
      postmortem seepage of blood. Three cases are described where such lesions caused
      concerns regarding the possibility of inflicted or accidental injury. These cases
      demonstrate that extensive skin loss and considerable hemorrhage may result from
      ant predation after death mimicking antemortem injury. This is particularly so in
      bodies that have been left outdoors, but it may also occur in bodies lying
      indoors. Problems may arise if ants have been removed or lost prior to postmortem
      assessment. 

PMID- 25869836
TI  - The estimation of the time since death using temperatures recorded from the
      external auditory canal : Part I: Can a temperature be recorded and interpreted
      from this site?
AB  - In this first paper of two, two experimental models are used to revisit and
      expand upon the question as to whether a temperature can be recorded from the
      external auditory canal (EAC) and used to estimate a time since death using the
      largest data series for this site to date. The behaviour of the temperature
      within the EAC after death is investigated and compared to that of the rectum.
      The temperatures are then applied to previously published algorithms to estimate
      the time since death. The choice of thermometer and the algorithm to be used are
      considered as well as why the time since death will be overestimated if
      consideration is not given to the differences between the rectal and EAC
      temperature in life or after death. 

PMID- 25869837
TI  - Mechanistic hypothesis for eye injury in infant shaking : An experimental and
      computational study.
AB  - The terms abusive head injury and shaken baby syndrome are used to describe a
      unique pattern of nonaccidental traumatic injuries occurring in children that
      many clinicians and researchers have good reason to believe is caused by violent
      shaking. Typical injuries include severe brain injury, with intracranial and
      retinal hemorrhages, but the pathogenesis of injuries is poorly understood. A
      major paradox in head trauma in infants is that the injuries induced by a shaking
      event are much more severe than those caused by even very violent single-impact
      head trauma, despite the relatively low accelerations in shaking.We have
      developed a finite element computer model of the eye, orbit, and orbital bone and
      used it to simulate the effects of single-impact and oscillatory motion inputs.
      The model was informed by data from semiquantitative in vitro anatomical traction
      experiments on in situ rabbit eyes. The new results reported here strongly
      suggest that suction between the eye and its surrounding fat dominates the
      dynamical stability of the system composed of the eye, its socket, and the
      components and material supporting the eye. Computer simulations incorporating
      this functional anatomical relationship show that deceleration of the head
      generates pressure gradients inside and outside the eye; these could cause
      damaging shear stresses in structures such as the retina and blood vessels.
      Simulations also show that oscillating the bone of the orbit causes the eye to
      move anteriorly and posteriorly with an increasing amplitude, building up the
      stresses within the eye over time. This is the first time that any biomechanical
      mechanism has been identified that might explain the disproportionally severe
      injuries caused by an oscillatory mechanism such as violent shaking of an abused
      infant. However, further study is required and this conclusion is therefore
      preliminary and provisional. 

PMID- 25869838
TI  - A screwdriver in the skull : A case report of an unusual finding.
AB  - The examination of the body of a murdered adult female found in her apartment
      revealed the presence of a 6-inch screwdriver in the skull cavity that had been
      inserted through the medial border of the left eye. The presence of a small
      bruise around the medial aspect of the eye together with the absence of fresh
      hemorrhage along the tract of the screwdriver was consistent with a postmortem
      origin. Death, however, was caused by a large incised wound of the neck and
      multiple skull fractures consistent with hammer blows. 

PMID- 25869839
TI  - Mini-STRs.
AB  - The use of the short-tandem repeat (STR) as the DNA marker of choice in forensic
      profiling has lead to the construction of criminal intelligence databases that
      now contain millions of profiles used in the detection and linking of suspects
      and scenes. The incredible size and success rate of current systems have ensured
      that efforts to move away from STR profiling and toward the use of alternate DNA
      markers are practically impossible, mainly because of the financial implications
      involved in such a move. Problems are routinely encountered when template DNA is
      of suboptimal condition, as is commonly the case in the forensic laboratory,
      whereby full profile generation of degraded samples is not possible. A redesigned
      amplification protocol that results in the generation of shorter polymerase chain
      reaction products yet is fully compatible with current STR databases has been
      introduced: the MiniPlex. 

PMID- 25869840
TI  - Microdosing of a Carbon-14 Labeled Protein in Healthy Volunteers Accurately
      Predicts Its Pharmacokinetics at Therapeutic Dosages.
AB  - Preclinical development of new biological entities (NBEs), such as human protein
      therapeutics, requires considerable expenditure of time and costs. Poor
      prediction of pharmacokinetics in humans further reduces net efficiency. In this
      study, we show for the first time that pharmacokinetic data of NBEs in humans can
      be successfully obtained early in the drug development process by the use of
      microdosing in a small group of healthy subjects combined with ultrasensitive
      accelerator mass spectrometry (AMS). After only minimal preclinical testing, we
      performed a first-in-human phase 0/phase 1 trial with a human recombinant
      therapeutic protein (RESCuing Alkaline Phosphatase, human recombinant placental
      alkaline phosphatase [hRESCAP]) to assess its safety and kinetics.
      Pharmacokinetic analysis showed dose linearity from microdose (53 MUg) [(14) C]
      hRESCAP to therapeutic doses (up to 5.3 mg) of the protein in healthy volunteers.
      This study demonstrates the value of a microdosing approach in a very small
      cohort for accelerating the clinical development of NBEs. 

PMID- 25869841
TI  - Flotation separation of waste plastics for recycling-A review.
AB  - The sharp increase of plastic wastes results in great social and environmental
      pressures, and recycling, as an effective way currently available to reduce the
      negative impacts of plastic wastes, represents one of the most dynamic areas in
      the plastics industry today. Froth flotation is a promising method to solve the
      key problem of recycling process, namely separation of plastic mixtures. This
      review surveys recent literature on plastics flotation, focusing on specific
      features compared to ores flotation, strategies, methods and principles,
      flotation equipments, and current challenges. In terms of separation methods,
      plastics flotation is divided into gamma flotation, adsorption of reagents,
      surface modification and physical regulation. 

PMID- 25869842
TI  - Use of genetic algorithms to improve the solid waste collection service in an
      urban area.
AB  - Increasing generation of Urban Solid Waste (USW) has become a significant issue
      in developing countries due to unprecedented population growth and high rates of
      urbanisation. This issue has exceeded current plans and programs of local
      governments to manage and dispose of USW. In this study, a Genetic Algorithm for
      Rule-set Production (GARP) integrated into a Geographic Information System (GIS)
      was used to find areas with socio-economic conditions that are representative of
      the generation of USW constituents in such areas. Socio-economic data of selected
      variables categorised by Basic Geostatistical Areas (BGAs) were taken from the
      2000 National Population Census (NPC). USW and additional socio-economic data
      were collected during two survey campaigns in 1998 and 2004. Areas for sampling
      of USW were stratified into lower, middle and upper economic strata according to
      income. Data on USW constituents were analysed using descriptive statistics and
      Multivariate Analysis. ARC View 3.2 was used to convert the USW data and socio
      economic variables to spatial data. Desk-top GARP software was run to generate a
      spatial model to identify areas with similar socio-economic conditions to those
      sampled. Results showed that socio-economic variables such as monthly income and
      education are positively correlated with waste constituents generated. The GARP
      used in this study revealed BGAs with similar socio-economic conditions to those
      sampled, where a similar composition of waste constituents generated is expected.
      Our results may be useful to decrease USW management costs by improving the
      collection services. 

PMID- 25869843
TI  - Deoxygenation of waste cooking oil and non-edible oil for the production of
      liquid hydrocarbon biofuels.
AB  - Deoxygenation of waste cooking vegetable oil and Jatropha curcas oil under
      nitrogen atmosphere was performed in batch and semi-batch experiments using CaO
      and treated hydrotalcite (MG70) as catalysts at 400  degrees C. In batch
      conditions a single liquid fraction (with yields greater than 80 wt.%) was
      produced containing a high proportion of hydrocarbons (83%). In semi-batch
      conditions two liquid fractions (separated by a distillation step) were obtained:
      a light fraction and an intermediate fraction containing amounts of hydrocarbons
      between 72-80% and 85-88% respectively. In order to assess the possible use of
      the liquid products as alternative fuels a complete chemical characterization and
      measurement of their properties were carried out.

PMID- 25869844
TI  - Comparative study on copper leaching from waste printed circuit boards by typical
      ionic liquid acids.
AB  - Waste printed circuit boards (WPCBs) are attracting increasing concerns because
      the recovery of its content of valuable metallic resources is hampered by the
      presence of hazardous substances. In this study, we used ionic liquids (IL) to
      leach copper from WPCBs. [BSO3HPy]OTf, [BSO3HMIm]OTf, [BSO4HPy]HSO4,
      [BSO4HMim]HSO4 and [MIm]HSO4 were selected. Factors that affect copper leaching
      rate were investigated in detail and their leaching kinetics were also examined
      with the comparison of [Bmim]HSO4. The results showed that all six IL acids could
      successfully leach copper out, with near 100% recovery. WPCB particle size and
      leaching time had similar influences on copper leaching performance, while IL
      acid concentration, hydrogen peroxide addition, solid to liquid ratio,
      temperature, showed different influences. Moreover, IL acid with HSO4(-) was more
      efficient than IL acid with CF3SO3(-). These six IL acids indicate a similar
      behavior with common inorganic acids, except temperature since copper leaching
      rate of some IL acids decreases with its increase. The results of leaching
      kinetics studies showed that diffusion plays a more important role than surface
      reaction, whereas copper leaching by inorganic acids is usually controlled by
      surface reaction. This innovation provides a new option for recovering valuable
      materials such as copper from WPCBs. 

PMID- 25869845
TI  - Smartphones are useful for disease surveillance in rural areas, study finds.

PMID- 25869846
TI  - Nurses Identify Education and Communication Among Professionals as Essential in
      Serving ASD Children.
AB  - Autism spectrum disorder (ASD) is a broad term encompassing a group of
      neurodevelopmental disabilities. Children with ASD present behavioral,
      communication, and social behaviors. One in 68 individuals is diagnosed with
      autism. With ASD prevalence continuing to rise, it makes sense for school nurses
      to identify areas that may be helpful in serving this population. This school
      nurse focus group study shared specific areas that would benefit school nurses
      when working with children with autism. Two glaring trends surfaced from the
      focus group--continuing education needs and communication among all school
      professionals (i.e., teachers, special education services).

PMID- 25869847
TI  - New bioactive flavonoid glycosides isolated from the seeds of Lepidium apetalum
      Willd.
AB  - Ten flavonoid glycosides, apetalumosides A (1), B1-B7 (2-8), and C (9), quercetin
      3-O-(2,6-di-O-beta-D-glucopyranosyl)-beta-D-glucopyranoside (10), were obtained
      from the seeds of Lepidium apetalum Willd. Their structures were elucidated by
      chemical and spectroscopic methods (UV, IR, NMR, and HRESI-TOF-MS). 1-9 were new
      isolates. The NMR data for 10 was reported here for the first time. On the other
      hand, activity screening results showed that 1-3 and 10 had triglyceride
      accumulation inhibitory effects in HepG2 cells. Preliminary structure-activity
      relationship study revealed that 7-hydroxyl group is an essential moiety.

PMID- 25869848
TI  - A renal-targeted triptolide aminoglycoside (TPAG) conjugate for lowering systemic
      toxicities of triptolide.
AB  - Triptolide (TP), a naturally derived compound, is proven effective in the
      treatment of nephritis and chronic allograft nephropathy. However, the severe
      multiorgan toxicity greatly limited it from further clinic use. 2-Glucosamine was
      demonstrated as a potential targeting ligand that could specifically interact
      with megalin receptors highly expressed in renal proximal tubules. In this study,
      2-glucosamine was employed as a glycosyl donor while triptolide the acceptor to
      afford a nonhydrolyzable triptolide derivative-triptolide aminoglycoside (TPAG).
      The kidney-targeting efficiency, pharmacodynamic properties and safety of TPAG
      were thus evaluated. TPAG displayed 6.94-fold of AUC(0-t, kidney) and 13.96-fold
      of MRT(0-t, kidney) compared to TP. Additionally, TPAG presented improved
      protective effect against renal ischemia/reperfusion injury. Compared to TP's
      multiorgan toxicity, TPAG showed minimum toxicity toward the kidney and genital
      systems, and greatly lowered toxicity in the liver and immune systems. In sum,
      our study presented an alternative structure modification of triptolide with
      improved safety and efficacy profiles.

PMID- 25869849
TI  - Fusarium redolens 6WBY3, an endophytic fungus isolated from Fritillaria
      unibracteata var. wabuensis, produces peimisine and imperialine-3beta-D
      glucoside.
AB  - The major biological active ingredients of Bulbus Fritillariae cirrhosae (BFC)
      are steroidal alkaloids, such as peimisine, imperialine-3beta-D-glucoside, and
      peimine. The bulbus of Fritillaria unibracteata var. wabuensis (FUW) was
      officially recorded in the National Pharmacopoeia of China (2010 edition) as one
      of the sources of BFC because of its positive therapeutic effects and few side
      effects. The endophytic fungus strain 6WBY3 was isolated from the fresh bulbus of
      FUW that had been cultivated for six years. Based on morphological methods and
      the phylogenetic analysis of internal transcribed spacer (ITS) sequences, this
      strain was identified as Fusarium redolens. Using color reaction analysis, high
      performance liquid chromatography with evaporative light scattering detection
      (HPLC-ELSD), and mass spectrometry (MS), it was demonstrated that F. redolens
      6WBY3 could produce peimisine and imperialine-3beta-D-glucoside, similar to its
      host plant. The yields of peimisine and imperialine-3beta-D-glucoside were 16.0
      MUg.l(-1) and 18.8 MUg.l(-1), respectively, in one week of culture. These results
      indicate that F. redolens 6WBY3 is a promising candidate for the large scale
      production of peimisine and imperialine-3beta-D-glucoside. In addition, the
      results from the strain 6WBY3 lay the foundation for further study into the
      mechanism of Fritillaria alkaloids biosynthesis in fungi.

PMID- 25869850
TI  - Attorney beliefs concerning scientific evidence and expert witness credibility.
AB  - Expert witnesses play a pivotal role in offering a variety of scientific evidence
      at trial. Although judges are the ultimate gatekeepers of what constitutes valid
      scientific evidence, attorneys play an important part in determining what
      evidence is presented to the court. Employing experimental and descriptive
      analyses, the present study sought to address gaps in the attorney/expert witness
      literature by addressing three questions: One) To what extent do attorneys prefer
      forensic or social scientific evidence and experts?, Two) How knowledgeable are
      attorneys concerning empirically-supported indicators of expert credibility?,
      Three) What do attorneys believe concerning the frequency and nature of expert
      errors in their own trials relative to others? Results showed that attorneys
      prefer forensic science evidence and experts compared to social/psychological
      counterparts. Moreover, attorneys displayed considerable knowledge of factors
      that will impact perceived expert credibility. In particular, attorneys value
      perceived expert trustworthiness, communication skills, content of
      testimony/reports, perceived expert knowledge, and years and type of expert
      experience. Finally, attorneys displayed a consistent and strong self-serving
      bias pattern, such that they believe expert errors occur more much frequently in
      other attorneys' cases compared to their own. Implications are discussed with
      respect to vetting expert witnesses, scientific evidence/errors and wrongful
      conviction, and training for attorneys. 

PMID- 25869852
TI  - Facilitation of soft tissue surgery: surgical staplers and vessel sealing
      devices.
AB  - Recent advances and acceptance of various medical devices have clearly helped in
      the efficiency, simplicity, and effectiveness of veterinary surgery. The goals of
      surgery include efficient methods and minimal surgical times, delicate tissue
      handling techniques, confidence with tissue reconstruction, and minimizing
      contamination, leakage and complications. Mechanical means of suturing, cutting,
      and hemostasis assist with accomplishing these goals. Most recently, stapling
      instrumentation and vascular sealing devices have become common instruments on
      all levels of surgery because of their ease of use and increase in surgical
      efficiency. 

PMID- 25869853
TI  - Thoracic surgery; important considerations and practical steps.
AB  - Thoracic surgery is a challenge for any veterinary surgeon. A review of several
      important articles on topics relative to thoracotomy procedures is presented.
      Discussion also includes an evaluation of availability of appropriate surgical
      facilities, necessary equipment before undertaking thoracic surgical procedures,
      and the essentials and pitfalls to making an approach and effectively closing the
      thoracic cavity of a dog or cat. This article reviews the 3 primary types of
      thoracotomy: lateral (intercostal) thoracotomy, median sternotomy, and
      transdiaphragmatic thoracotomy. Essential anatomy, surgical approach, and various
      techniques to ensure effective and durable thoracotomy closure are presented. 

PMID- 25869851
TI  - Functional connectivity of visual cortex in the blind follows retinotopic
      organization principles.
AB  - Is visual input during critical periods of development crucial for the emergence
      of the fundamental topographical mapping of the visual cortex? And would this
      structure be retained throughout life-long blindness or would it fade as a result
      of plastic, use-based reorganization? We used functional connectivity magnetic
      resonance imaging based on intrinsic blood oxygen level-dependent fluctuations to
      investigate whether significant traces of topographical mapping of the visual
      scene in the form of retinotopic organization, could be found in congenitally
      blind adults. A group of 11 fully and congenitally blind subjects and 18 sighted
      controls were studied. The blind demonstrated an intact functional connectivity
      network structural organization of the three main retinotopic mapping axes:
      eccentricity (centre-periphery), laterality (left-right), and elevation (upper
      lower) throughout the retinotopic cortex extending to high-level ventral and
      dorsal streams, including characteristic eccentricity biases in face- and house
      selective areas. Functional connectivity-based topographic organization in the
      visual cortex was indistinguishable from the normally sighted retinotopic
      functional connectivity structure as indicated by clustering analysis, and was
      found even in participants who did not have a typical retinal development in
      utero (microphthalmics). While the internal structural organization of the visual
      cortex was strikingly similar, the blind exhibited profound differences in
      functional connectivity to other (non-visual) brain regions as compared to the
      sighted, which were specific to portions of V1. Central V1 was more connected to
      language areas but peripheral V1 to spatial attention and control networks. These
      findings suggest that current accounts of critical periods and experience
      dependent development should be revisited even for primary sensory areas, in that
      the connectivity basis for visual cortex large-scale topographical organization
      can develop without any visual experience and be retained through life-long
      experience-dependent plasticity. Furthermore, retinotopic divisions of labour,
      such as that between the visual cortex regions normally representing the fovea
      and periphery, also form the basis for topographically-unique plastic changes in
      the blind. 

PMID- 25869854
TI  - beta-Isocyanoalanine as an IR probe: comparison of vibrational dynamics between
      isonitrile and nitrile-derivatized IR probes.
AB  - An infrared (IR) probe based on isonitrile (NC)-derivatized alanine 1 was
      synthesized and the vibrational properties of its NC stretching mode were
      investigated using FTIR and femtosecond IR pump-probe spectroscopy. It is found
      that the NC stretching mode is very sensitive to the hydrogen-bonding ability of
      solvent molecules. Moreover, its transition dipole strength is larger than that
      of nitrile (CN) in nitrile-derivatized IR probe 2. The vibrational lifetime of
      the NC stretching mode is found to be 5.5 +/- 0.2 ps in both D2O and DMF
      solvents, which is several times longer than that of the azido (N3) stretching
      mode in azido-derivatized IR probe 3. Altogether these properties suggest that
      the NC group can be a very promising sensing moiety of IR probes for studying the
      solvation structure and dynamics of biomolecules.

PMID- 25869856
TI  - Simulating disease propagation across white matter connectome reveals anatomical
      substrate for neuropathology staging in amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease,
      characterized by progressive loss of motor function. While the pathogenesis of
      ALS remains largely unknown, recent histological examinations of Brettschneider
      and colleagues have proposed four time-sequential stages of neuropathology in ALS
      based on levels of phosphorylated 43kDa TAR DNA-binding protein (pTDP-43)
      aggregation. What governs dissemination of these aggregates between segregated
      regions of the brain is unknown. Here, we cross-reference stages of pTDP-43
      pathology with in vivo diffusion weighted imaging data of 215 adult healthy
      control subjects, and reveal that regions involved in pTDP-43 pathology form a
      strongly interconnected component of the brain network (p=0.04) likely serving as
      an anatomical infrastructure facilitating pTDP-43 spread. Furthermore, brain
      regions of subsequent stages of neuropathology are shown to be more closely
      interconnected than regions of more distant stages (p=0.002). Computational
      simulation of disease spread from first-stage motor regions across the
      connections of the brain network reveals a pattern of pTDP-43 aggregation that
      reflects the stages of sequential involvement in neuropathology (p=0.02), a
      pattern in favor of the hypothesis of pTDP-43 pathology to spread across the
      brain along axonal pathways. Our findings thus provide computational evidence of
      disease spread in ALS to be directed and constrained by the topology of the
      anatomical brain network.

PMID- 25869855
TI  - Robust regeneration of adult zebrafish lateral line hair cells reflects continued
      precursor pool maintenance.
AB  - We have examined lateral line hair cell and support cell maintenance in adult
      zebrafish when growth is largely complete. We demonstrate that adult zebrafish
      not only replenish hair cells after a single instance of hair cell damage, but
      also maintain hair cells and support cells after multiple rounds of damage and
      regeneration. We find that hair cells undergo continuous turnover in adult
      zebrafish in the absence of damage. We identify mitotically-distinct support cell
      populations and show that hair cells regenerate from underlying support cells in
      a region-specific manner. Our results demonstrate that there are two distinct
      support cell populations in the lateral line, which may help explain why
      zebrafish hair cell regeneration is extremely robust, retained throughout life,
      and potentially unlimited in regenerative capacity. 

PMID- 25869857
TI  - The organisation of the elderly connectome.
AB  - Investigations of the human connectome have elucidated core features of adult
      structural networks, particularly the crucial role of hub-regions. However,
      little is known regarding network organisation of the healthy elderly connectome,
      a crucial prelude to the systematic study of neurodegenerative disorders. Here,
      whole-brain probabilistic tractography was performed on high-angular diffusion
      weighted images acquired from 115 healthy elderly subjects (age 76-94 years; 65
      females). Structural networks were reconstructed between 512 cortical and
      subcortical brain regions. We sought to investigate the architectural features of
      hub-regions, as well as left-right asymmetries, and sexual dimorphisms. We
      observed that the topology of hub-regions is consistent with a young adult
      population, and previously published adult connectomic data. More importantly,
      the architectural features of hub connections reflect their ongoing vital role in
      network communication. We also found substantial sexual dimorphisms, with females
      exhibiting stronger inter-hemispheric connections between cingulate and
      prefrontal cortices. Lastly, we demonstrate intriguing left-lateralized
      subnetworks consistent with the neural circuitry specialised for language and
      executive functions, whilst rightward subnetworks were dominant in visual and
      visuospatial streams. These findings provide insights into healthy brain ageing
      and provide a benchmark for the study of neurodegenerative disorders such as
      Alzheimer's disease (AD) and frontotemporal dementia (FTD).

PMID- 25869858
TI  - Brain functional plasticity associated with the emergence of expertise in extreme
      language control.
AB  - We used functional magnetic resonance imaging (fMRI) to longitudinally examine
      brain plasticity arising from long-term, intensive simultaneous interpretation
      training. Simultaneous interpretation is a bilingual task with heavy executive
      control demands. We compared brain responses observed during simultaneous
      interpretation with those observed during simultaneous speech repetition
      (shadowing) in a group of trainee simultaneous interpreters, at the beginning and
      at the end of their professional training program. Age, sex and language
      proficiency matched controls were scanned at similar intervals. Using
      multivariate pattern classification, we found distributed patterns of changes in
      functional responses from the first to second scan that distinguished the
      interpreters from the controls. We also found reduced recruitment of the right
      caudate nucleus during simultaneous interpretation as a result of training. Such
      practice-related change is consistent with decreased demands on multilingual
      language control as the task becomes more automatized with practice. These
      results demonstrate the impact of simultaneous interpretation training on the
      brain functional response in a cerebral structure that is not specifically
      linguistic, but that is known to be involved in learning, in motor control, and
      in a variety of domain-general executive functions. Along with results of recent
      studies showing functional and structural adaptations in the caudate nuclei of
      experts in a broad range of domains, our results underline the importance of this
      structure as a central node in expertise-related networks. 

PMID- 25869859
TI  - The encoding of category-specific versus nonspecific information in human
      inferior temporal cortex.
AB  - Several brain areas in the inferior temporal (IT) cortex, such as the fusiform
      face area (FFA) and parahippocampal place area (PPA), are hypothesized to be
      selectively responsive to a particular category of visual objects. However, how
      category-specific and nonspecific information may be encoded at this level of
      visual processing is still unclear. Using fMRI, we compared averaged BOLD
      activity as well as multi-voxel activation patterns in the FFA and PPA
      corresponding to high-contrast and low-contrast face and house images. The
      averaged BOLD activity in the FFA and PPA was modulated by the image contrast
      regardless of the stimulus category. Interestingly, unlike the univariate
      averaged BOLD activity, multi-voxel activation patterns in the FFA and PPA were
      barely affected by variations in stimulus contrast. In both the FFA and PPA,
      decoding the categorical information about whether participants saw faces or
      houses was independent of stimulus contrast. Moreover, the multivariate pattern
      analysis (MVPA) results were highly stable when either the voxels that were more
      sensitive to stimulus contrast or the voxels that were less sensitive were used.
      Taken together, these findings demonstrate that both category-specific (face
      versus house) information and nonspecific (image contrast) information are
      available to be decoded orthogonally in the same brain areas (FFA and PPA),
      suggesting that complementary neural mechanisms for processing visual features
      and categorical information may occur in the same brain areas but respectively be
      revealed by averaged activity and multi-voxel activation patterns. Whereas
      stimulus strength, such as contrast, modulates overall activity amplitudes in
      these brain areas, activity patterns across populations of neurons appear to
      underlie the representation of object category. 

PMID- 25869860
TI  - BOLD fMRI study of ultrahigh frequency encoding in the inferior colliculus.
AB  - Many vertebrates communicate with ultrahigh frequency (UHF) vocalizations to
      limit auditory detection by predators. The mechanisms underlying the neural
      encoding of such UHF sounds may provide important insights for understanding
      neural processing of other complex sounds (e.g. human speeches). In the auditory
      system, sound frequency is normally encoded topographically as tonotopy, which,
      however, contains very limited representation of UHFs in many species. Instead,
      electrophysiological studies suggested that two neural mechanisms, both
      exploiting the interactions between frequencies, may contribute to UHF
      processing. Neurons can exhibit excitatory or inhibitory responses to a tone when
      another UHF tone is presented simultaneously (combination sensitivity). They can
      also respond to such stimulation if they are tuned to the frequency of the
      cochlear-generated distortion products of the two tones, e.g. their difference
      frequency (cochlear distortion). Both mechanisms are present in an early station
      of the auditory pathway, the midbrain inferior colliculus (IC). Currently, it is
      unclear how prevalent the two mechanisms are and how they are functionally
      integrated in encoding UHFs. This study investigated these issues with large-view
      BOLD fMRI in rat auditory system, particularly the IC. UHF vocalizations (above
      40kHz), but not pure tones at similar frequencies (45, 55, 65, 75kHz), evoked
      robust BOLD responses in multiple auditory nuclei, including the IC, reinforcing
      the sensitivity of the auditory system to UHFs despite limited representation in
      tonotopy. Furthermore, BOLD responses were detected in the IC when a pair of UHF
      pure tones was presented simultaneously (45 & 55kHz, 55 & 65kHz, 45 & 65kHz, 45 &
      75kHz). For all four pairs, a cluster of voxels in the ventromedial side always
      showed the strongest responses, displaying combination sensitivity. Meanwhile,
      voxels in the dorsolateral side that showed strongest secondary responses to each
      pair of UHF pure tones also showed the strongest responses to a pure tone at
      their difference frequency, suggesting that they are sensitive to cochlear
      distortion. These BOLD fMRI results indicated that combination sensitivity and
      cochlear distortion are employed by large but spatially distinctive neuron
      populations in the IC to represent UHFs. Our imaging findings provided insights
      for understanding sound feature encoding in the early stage of the auditory
      pathway. 

PMID- 25869861
TI  - Local field potentials in primate motor cortex encode grasp kinetic parameters.
AB  - Reach and grasp kinematics are known to be encoded in the spiking activity of
      neuronal ensembles and in local field potentials (LFPs) recorded from primate
      motor cortex during movement planning and execution. However, little is known,
      especially in LFPs, about the encoding of kinetic parameters, such as forces
      exerted on the object during the same actions. We implanted two monkeys with
      microelectrode arrays in the motor cortical areas MI and PMd to investigate
      encoding of grasp-related parameters in motor cortical LFPs during planning and
      execution of reach-and-grasp movements. We identified three components of the LFP
      that modulated during grasps corresponding to low (0.3-7Hz), intermediate (~10
      ~40Hz) and high (~80-250Hz) frequency bands. We show that all three components
      can be used to classify not only grip types but also object loads during planning
      and execution of a grasping movement. In addition, we demonstrate that all three
      components recorded during planning or execution can be used to continuously
      decode finger pressure forces and hand position related to the grasping movement.
      Low and high frequency components provide similar classification and decoding
      accuracies, which were substantially higher than those obtained from the
      intermediate frequency component. Our results demonstrate that intended reach and
      grasp kinetic parameters are encoded in multiple LFP bands during both movement
      planning and execution. These findings also suggest that the LFP is a reliable
      signal for the control of parameters related to object load and applied pressure
      forces in brain-machine interfaces. 

PMID- 25869862
TI  - 3D mapping of neuronal migration in the embryonic mouse brain with magnetic
      resonance microimaging.
AB  - A prominent feature of the developing mammalian brain is the widespread migration
      of neural progenitor (NP) cells during embryogenesis. A striking example is
      provided by NP cells born in the ventral forebrain of mid-gestation stage mice,
      which subsequently migrate long distances to their final positions in the cortex
      and olfactory bulb. Previous studies have used two-dimensional histological
      methods, making it difficult to analyze three-dimensional (3D) migration
      patterns. Unlike histology, magnetic resonance microimaging (micro-MRI) is a non
      destructive, quantitative and inherently 3D imaging method for analyzing mouse
      embryos. To allow mapping of migrating NP cells with micro-MRI, cells were
      labeled in situ in the medial (MGE) and lateral (LGE) ganglionic eminences, using
      targeted in utero ultrasound-guided injection of micron-sized particles of iron
      oxide (MPIO). Ex vivo micro-MRI and histology were then performed 5-6days after
      injection, demonstrating that the MPIO had magnetically labeled the migrating NP
      populations, which enabled 3D visualization and automated segmentation of the
      labeled cells. This approach was used to analyze the distinct patterns of
      migration from the MGE and LGE, and to construct rostral-caudal migration maps
      from each progenitor region. Furthermore, abnormal migratory phenotypes were
      observed in Nkx2.1(-/-) embryos, most notably a significant increase in cortical
      neurons derived from the Nkx2.1(-/-) LGE. Taken together, these results
      demonstrate that MPIO labeling and micro-MRI provide an efficient and powerful
      approach for analyzing 3D cell migration patterns in the normal and mutant mouse
      embryonic brain. 

PMID- 25869864
TI  - Effects of nanoscopic-confinement on polymer dynamics.
AB  - The static and dynamic behavior of polymers in confinement close to interfaces
      can be very different from that in the bulk. Among the various geometries,
      intercalated nanocomposites, in which polymer films of ~1 nm thickness reside
      between the parallel inorganic surfaces of layered silicates in a well-ordered
      multilayer, offer a unique avenue for the investigation of the effects of
      nanoconfinement on polymer structure and dynamics by utilizing conventional
      analytical techniques and macroscopic specimens. In this article, we provide a
      review of research activities mainly in our laboratory on polymer dynamics under
      severe confinement utilizing different polymer systems: polar and non-polar
      polymers were mixed with hydrophilic or organophilic silicates, respectively,
      whereas hyperbranched polymers were studied in an attempt to probe the effect of
      polymer-surface interactions by altering the number and the kinds of functional
      groups in the periphery of the branched polymers. The polymer dynamics was probed
      by quasielastic neutron scattering and dielectric relaxation spectroscopy and was
      compared with that of the polymers in the bulk. In all cases, very local sub-Tg
      processes related to the motion of side and/or end groups as well as the
      segmental alpha-relaxation were identified with distinct differences recorded
      between the bulk and the confined systems. Confinement was found not to affect
      the very local motion in the case of the linear chains whereas it made it easier
      for hyperbranched polymers due to modifications of the hydrogen bond network. The
      segmental relaxation in confinement becomes faster than that in the bulk,
      exhibits Arrhenius temperature dependence and is observed even below the bulk Tg
      due to reduced cooperativity in the confined systems. 

PMID- 25869863
TI  - NeuroVault.org: A repository for sharing unthresholded statistical maps,
      parcellations, and atlases of the human brain.
AB  - NeuroVault.org is dedicated to storing outputs of analyses in the form of
      statistical maps, parcellations and atlases, a unique strategy that contrasts
      with most neuroimaging repositories that store raw acquisition data or
      stereotaxic coordinates. Such maps are indispensable for performing meta
      analyses, validating novel methodology, and deciding on precise outlines for
      regions of interest (ROIs). NeuroVault is open to maps derived from both healthy
      and clinical populations, as well as from various imaging modalities (sMRI, fMRI,
      EEG, MEG, PET, etc.). The repository uses modern web technologies such as
      interactive web-based visualization, cognitive decoding, and comparison with
      other maps to provide researchers with efficient, intuitive tools to improve the
      understanding of their results. Each dataset and map is assigned a permanent
      Universal Resource Locator (URL), and all of the data is accessible through a
      REST Application Programming Interface (API). Additionally, the repository
      supports the NIDM-Results standard and has the ability to parse outputs from
      popular FSL and SPM software packages to automatically extract relevant metadata.
      This ease of use, modern web-integration, and pioneering functionality holds
      promise to improve the workflow for making inferences about and sharing whole
      brain statistical maps. 

PMID- 25869865
TI  - GMC is criticised for refusing to disclose reasons behind its advice to support
      prescribing for Lucentis rather than Avastin for wet AMD.

PMID- 25869868
TI  - Should medicine take over tattoo removal?

PMID- 25869869
TI  - Apple moves into medical research.

PMID- 25869867
TI  - Prospective validation of a 1-hour algorithm to rule-out and rule-in acute
      myocardial infarction using a high-sensitivity cardiac troponin T assay.
AB  - BACKGROUND: We aimed to prospectively validate a novel 1-hour algorithm using
      high-sensitivity cardiac troponin T measurement for early rule-out and rule-in of
      acute myocardial infarction (MI). METHODS: In a multicentre study, we enrolled
      1320 patients presenting to the emergency department with suspected acute MI. The
      high-sensitivity cardiac troponin T 1-hour algorithm, incorporating baseline
      values as well as absolute changes within the first hour, was validated against
      the final diagnosis. The final diagnosis was then adjudicated by 2 independent
      cardiologists using all available information, including coronary angiography,
      echocardiography, follow-up data and serial measurements of high-sensitivity
      cardiac troponin T levels. RESULTS: Acute MI was the final diagnosis in 17.3% of
      patients. With application of the high-sensitivity cardiac troponin T 1-hour
      algorithm, 786 (59.5%) patients were classified as "rule-out," 216 (16.4%) were
      classified as "rule-in" and 318 (24.1%) were classified to the "observational
      zone." The sensitivity and the negative predictive value for acute MI in the rule
      out zone were 99.6% (95% confidence interval [CI] 97.6%-99.9%) and 99.9% (95% CI
      99.3%-100%), respectively. The specificity and the positive predictive value for
      acute MI in the rule-in zone were 95.7% (95% CI 94.3%-96.8%) and 78.2% (95% CI
      72.1%-83.6%), respectively. The 1-hour algorithm provided higher negative and
      positive predictive values than the standard interpretation of highsensitivity
      cardiac troponin T using a single cut-off level (both p < 0.05). Cumulative 30
      day mortality was 0.0%, 1.6% and 1.9% in patients classified in the rule-out,
      observational and rule-in groups, respectively (p = 0.001). INTERPRETATION: This
      rapid strategy incorporating high-sensitivity cardiac troponin T baseline values
      and absolute changes within the first hour substantially accelerated the
      management of suspected acute MI by allowing safe rule-out as well as accurate
      rule-in of acute MI in 3 out of 4 patients. TRIAL REGISTRATION:
      ClinicalTrials.gov, NCT00470587.

PMID- 25869870
TI  - Social egg freezing: risk, benefits and other considerations.

PMID- 25869872
TI  - A 30-year-old woman with vision loss and painful eye movements.

PMID- 25869873
TI  - Subungual malignant melanoma.

PMID- 25869874
TI  - TB: fighting a forgotten disease in Canada.

PMID- 25869876
TI  - Carbon monoxide-isocyanide coupling promoted by acetylide addition to a diiron
      complex.
AB  - C-N bond formation involving carbon monoxide and isocyanide ligands is promoted
      by addition of a series of lithium acetylides to a diiron MU-aminocarbyne
      complex, i.e. [Fe2{MU-CN(Me)(Xyl)}(MU-CO)(CO)(CNXyl)(Cp)2][SO3CF3] (Xyl = 2,6
      C6H3Me2). The reaction proceeds in three steps, i.e. (a) acetylide addition to
      the CO ligand, (b) acetylide migration to the isocyanide ligand, and (c) C-N
      coupling. The X-ray molecular structures of 1a and 1b comprise the first example
      of a kappa(C,C')-N-carbonyl-aminocarbene ligand. 

PMID- 25869875
TI  - Effects of exercise training on arterial stiffness in older hypertensive females.
AB  - PURPOSE: Regular physical exercise is recommended for the prevention and
      treatment of cardiovascular disease. However, it is unclear whether the effects
      of exercise training on arterial stiffness are the same in older hypertensive
      individuals as those observed in older healthy subjects. The aim of this study
      was to compare the effects of exercise training on arterial stiffness between
      older hypertensive and healthy females. METHODS: Ninety-two females with
      untreated hypertension and 108 healthy females were randomly assigned to either
      the control group or to participate in a 12-week training program. In the
      training groups, the subjects engaged in 90 min of training twice a week for 12
      weeks. Each training program included recreational activities, six to eight
      resistance exercises for circuit training and chair-based exercise for the lower
      extremities. The systolic/diastolic blood pressure (SBP/DBP) and brachial to
      ankle pulse wave velocity (baPWV) were obtained in the supine position using an
      automatic pulse wave form analyzer. RESULTS: Compared with that observed in the
      control group, greater reductions in the baPWV and SBP/DBP were achieved in both
      training groups (P < 0.05). Furthermore, a significant difference in the delta
      baPWV values obtained before and after training was noted between the
      hypertensive (-72.5 +/- 8.1 cm s(-1)) and healthy females (-131.5 +/- 107.3 cm s(
      1)) who participated in the training program (P < 0.05). CONCLUSIONS: These data
      indicate that exercise training produces fewer improvements in arterial stiffness
      in older hypertensive females than in older healthy females.

PMID- 25869877
TI  - Prognostic value of microRNA-10b overexpression in peripheral blood mononuclear
      cells of nonsmall-cell lung cancer patients.
AB  - We examined microRNA (miRNA)-10b expression in peripheral blood mononuclear cells
      (PBMCs) of nonsmall-cell lung cancer (NSCLC) patients for its clinical value. A
      group of 74 patients confirmed with NSCLC were recruited as case group and 52
      healthy volunteers as control group. PBMCs were isolated from all subjects, and
      miRNA-10b expression level in these cells was measured by reverse transcription
      quantitative real-time polymerase chain reaction (qRT-PCR). The correlation
      between miRNA-10b expression levels and the clinical and pathological
      characteristics of NSCLC was obtained. The miRNA-10b expression level in NSCLS
      patients is markedly higher than control subjects (P < 0.01). Analysis of
      receiver operating characteristic (ROC) curve estimated the peak diagnostic
      sensitivity of miRNA-10b at 86.5 % and specificity at 76.9 %. NSCLC patients were
      divided into high expression group (64 patients) and low expression group (10
      patients). Further analysis showed that miRNA-10b expression levels in PBMCs
      correlated with lymph node metastasis, distant metastasis, and TNM classification
      (all P < 0.05). The 5-year survival rate in high expression group was
      significantly lower than low expression group (P = 0.017). Multivariate analysis
      by Cox regression model showed that high miRNA-10b expression, age >60 years,
      lymph node and distant metastases, and stage III-IV carcinoma were risk factors
      for poor prognosis in NSCLC patients (all P < 0.05). MiRNA-10b expression levels
      in PBMCs can distinguish NSCLC patients from cancer-free subjects with a high
      sensitivity and specificity, suggesting that miRNA-10b expression in PBMCs is a
      valuable diagnostic and prognostic marker in NSCLC.

PMID- 25869878
TI  - Coexpression of c-Met and Notch-1 correlates with poor prognosis in resected non
      small-cell lung cancer.
AB  - Despite considerable advances in chemotherapy, radiotherapy, target therapy, and
      biological therapy, the prognosis for those with resected non-small-cell lung
      cancer (NSCLC) has not substantially improved. It was recently reported that two
      receptors, Notch-1 and c-Met, correlate directly or indirectly with the
      initiation and development of malignant tumors, such as lung cancer; however, the
      prognostic value of coexpression of these receptors and their relationship in
      resected NSCLC was not clear. In this study, the expression levels of Notch-1 and
      c-Met in 117 patients with resected NSCLC were assessed using
      immunohistochemistry (IHC). The results showed that the positive expression rate
      of Notch-1 in total patients was 59.8 %. The positive expression rate of c-Met in
      the all population was 69.2 %. In addition, a significant positive association
      was shown between Notch-1 and c-Met (P < 0.001). Simultaneously, patients with
      coexpression of both receptors had a significantly poorer prognosis than those
      without coexpression (P < 0.001). Multivariate analysis showed that T stage (P =
      0.016) and c-Met expression (P < 0.001) were independent prognostic factors. In
      conclusion, coexpression of both receptors correlates with poorer prognosis in
      patients with resected NSCLC. Targeting both receptors simultaneously may prove a
      more effective antitumor strategy. Patients with coexpression of both receptors
      might benefit from cotargeting Notch-1 and c-Met.

PMID- 25869879
TI  - The high expression of TC1 (C8orf4) was correlated with the expression of beta
      catenin and cyclin D1 and the progression of squamous cell carcinomas of the
      tongue.
AB  - Thyroid cancer 1 (TC1, C8orf4) plays important roles in many signaling pathways,
      such as Wnt/beta-catenin signaling pathway, and is involved in the development of
      many cancers. The objective of this study was to examine the expression of TC1
      and investigate the associations among TC1, beta-catenin, Chibby, cyclin D1, and
      the clinicopathological factors of oral tongue squamous cell carcinomas (OTSCCs).
      The expressions of TC1, beta-catenin, Chibby, and cyclin D1 were examined in 109
      cases of OTSCCs using immunohistochemistry. The expression of TC1 was observed in
      all cases of OTSCCs but was negative or weak in normal squamous epithelial
      tissues of tongue. The high expression of TC1 was correlated with the advanced
      TNM stage (P = 0.042), the abnormal expression of beta-catenin (correlation
      coefficient = 0.314, P = 0.001) and the expression of cyclin D1 (correlation
      coefficient = 0.274, P = 0.006) in OTSCCs. But we did not find any associations
      between TC1 and Chibby. The abnormal expression of beta-catenin was correlated
      with the poor differentiation (P = 0.035), advanced TNM stage (P = 0.048) and the
      expression of cyclin D1 (correlation coefficient = 0.422, P < 0.001). In
      conclusion, the high expression of TC1 was common in OTSCCs and correlated with
      the expression of beta-catenin and cyclin D1 and the progression of OTSCCs. The
      high expression level of TC1 might promote the progression of OTSCCs by enhancing
      the activity of Wnt signaling pathway. 

PMID- 25869880
TI  - Engineering human rhinovirus serotype-A1 as a vaccine vector.
AB  - Herein we describe the construction of recombinant human rhinoviruses (rHRVs)
      encoding HIV Gag or Tat by inserting the full length tat gene or regions of the
      gag gene flanked by sequences encoding the HRV 2A protease cleavage site into the
      junction between HRV genes encoding structural (P1) and non-structural (P2)
      proteins. Most recombinants were unstable, but this was corrected by mutation of
      the flanking cleavage sites. Thereafter, all rHRV constructs retained the inserts
      throughout six passages. Such constructs may find utility as vaccine vectors to
      generate mucosal immunity. 

PMID- 25869881
TI  - Naturally occurring reassortant infectious bursal disease virus in northern
      China.
AB  - Infectious bursal disease virus (IBDV) is a bi-segmented, double-stranded RNA
      virus that belongs to the genus Avibirnavirus of the family of Birnavirideae. The
      co-evolution of genome segments is a major evolutionary feature for IBDV.
      However, in recent years, some strains exhibited markedly different genetic
      relationships for segments A and B. In this study, we firstly isolated a new type
      of reassortment IBDV strain named IBD13HeB01 from northern China. The full-length
      genomes of segments A and B were cloned and identified. Sequence analysis
      revealed that IBD13HeB01 was a segment-reassortment strain, whose segment A was
      derived from very virulent strain and segment B from attenuated IBDV. In
      addition, the virulence of IBD13HeB01 strain was evaluated using SPF chickens.
      This study is not only beneficial for further understanding of the viral
      evolution but also suggests the potential risk of application of the live
      vaccines of IBDV. 

PMID- 25869882
TI  - SnX (X = S, Se) thin films as cost-effective and highly efficient counter
      electrodes for dye-sensitized solar cells.
AB  - Solution-deposited SnSe and SnS thin films demonstrate excellent electrocatalytic
      activity toward the triiodide reduction in dye-sensitized solar cells (DSCs),
      even better than that of the conventional noble Pt electrode used in DSCs. An
      enhanced photovoltaic efficiency with the maximum value of 9.4% was thus
      achieved, higher than that with Pt (9.0%). 

PMID- 25869883
TI  - Mississippi Communities for Healthy Living: Implementing a nutrition intervention
      effectiveness study in a rural health disparate region.
AB  - BACKGROUND: Intervention research in rural, health disparate communities presents
      unique challenges for study design, implementation, and evaluation. Challenges
      include 1) culturally appropriate intervention components, 2) participant
      recruitment and retention, 3) treatment cross-contamination, 4) intervention
      delivery and data collection, and 5) potential measurement reactivity. PURPOSE:
      The purposes of this paper are to 1) detail the methods of the MCHL study and 2)
      report baseline demographic characteristics of study participants. The secondary
      aim is to determine if study participants were engaging in behavior changes after
      enrollment and prior to intervention initiation. METHODS: MCHL was developed
      using the RE-AIM planning and evaluation framework (reach, effectiveness,
      adoption, implementation, maintenance). Intervention components were based on
      Roger's diffusion of innovation attributes that promote adoption of a new
      innovation as well as on the psychosocial constructs of social support, self
      efficacy and decisional balance. Rolling enrollment data collection was used to
      acquire sufficient sample size and a second data collection just prior to
      intervention implementation assessed measurement reactivity effects. Participant
      outcomes included diet quality, blood pressure, weight status, and quality of
      life. Cluster stratified assignment to one of two treatment arms was utilized to
      minimize cross contamination. Generalized linear models were used to compare
      enrollment measures between the two treatment arms while mixed model linear
      regression was used to test for changes in diet quality outcomes from enrollment
      to pre-intervention baseline. RESULTS: There were no significant differences in
      participant demographic, anthropometric or clinical measures between the two
      treatment arms at enrollment. With the exception of total vegetables, none of the
      diet quality indicators were significantly different between enrollment and
      baseline timepoints. CONCLUSIONS: Conducting nutrition intervention research in a
      rural health disparate region requires flexibility in adapting the recruitment,
      retention, and data collection procedures while maintaining a high level of
      scientific rigor. Negligible research participation effects, such as measurement
      reactivity, were noted in this population. However, further research is needed to
      identify methods to successfully recruit and retain Caucasian females to
      participate in community-based nutrition interventions in this region.

PMID- 25869884
TI  - Discontinuing the Use of PRN Intramuscular Medication for Agitation in an Acute
      Psychiatric Hospital.
AB  - This study examined the impact of eliminating intramuscular PRN medication for
      agitation on patient and staff safety in an acute psychiatric inpatient setting.
      The current retrospective chart review investigated the use of PRN medications
      (oral and intramuscular) to treat acute agitation, including aggression, and
      related outcomes before and after a mandated change in PRN practice that required
      real time physician input before administration of intramuscular medications. The
      use of both oral and intramuscular PRN medications dramatically decreased
      following implementation of the mandated change in practice. In particular, the
      use of intramuscular PRNs for agitation decreased by about half. Despite this
      decrease, the assault rate in the hospital was unchanged, and the utilization of
      restraint and seclusion continued to decrease. It is possible to reduce the
      utilization of PRN medications for agitation without broadly compromising safety
      on acute care psychiatric inpatient units. 

PMID- 25869885
TI  - Comparison of urine analysis and dried blood spot analysis for the detection of
      ephedrine and methylephedrine in doping control.
AB  - When the misuse of stimulants is determined in doping control tests conducted
      during the in-competition period, athletes are asked to account for the violation
      of the rules. This study was designed to evaluate whether the urinary threshold
      values (10 ug/mL) for ephedrine and methylephedrine set by the World Anti-Doping
      Agency (WADA) can be exceeded after the oral administration of each substance (25
      mg). In addition, the study describes the validity of a liquid chromatography
      tandem mass spectrometric method using dried blood spot testing to detect
      ephedrine and methylephedrine by comparing it to a quantitative laboratory urine
      assay. After administration of ephedrine, the urinary concentration of ephedrine
      did not exceed the threshold at 4-10 h in two subjects, whereas the threshold was
      exceeded in both the subjects at 12 h after administration. For methylephedrine,
      the urinary concentrations of all the subjects failed to reach the threshold for
      up to 10 h after administration. The concentrations reached the threshold at 12
      24 h after administration in some volunteers. In contrast, the blood
      concentrations of ephedrine and methylephedrine reached their maximum levels at 2
      8 h after administration. The blood concentrations showed a low inter-individual
      variability, and the results suggested that the urinary excretion of ephedrine
      and methylephedrine can be strongly affected by urine pH and/or urine volume.
      These facts suggest that urinary concentrations cannot reflect the psychoactive
      level of ephedrines in circulation. Thus, dried blood analysis might be suitable
      for the adequate detection of stimulants during in-competition testing.

PMID- 25869886
TI  - Nudges or mandates? The ethics of mandatory flu vaccination.
AB  - According to the CDC report for the 2012-2013 influenza season, there was a
      modest increase in the vaccination coverage rate among healthcare workers from
      67% in 2011-2012, to 72% in 2012-2013 to the current 75% coverage. This is still
      far from reaching the US National Healthy People 2020 goal of 90% hospitals
      vaccination rates. The reported increase in coverage is attributed to the growing
      number of healthcare facilities with vaccination requirements with average rates
      of 96.5%. However, a few other public health interventions stir so much
      controversy and debate as vaccination mandates. The opposition stems from the
      belief that a mandatory flu shot policy violates an individual right to refuse
      unwanted treatment. This article outlines the historic push to achieve higher
      vaccination rates among healthcare professionals and a number of ethical issues
      arising from attempts to implement vaccination mandates. It then turns to a
      review of cognitive biases relevant in the context of decisions about influenza
      vaccination (omission bias, ambiguity aversion, present bias etc.) The article
      suggests that a successful strategy for policy-makers and others hoping to
      increase vaccination rates is to design a "choice architecture" that influences
      behavior of healthcare professionals without foreclosing other options. Nudges
      incentivize vaccinations and help better align vaccination intentions with near
      term actions. 

PMID- 25869887
TI  - Intermediate rough Brucella abortus S19Deltaper mutant is DIVA enable, safe to
      pregnant guinea pigs and confers protection to mice.
AB  - Brucella abortus S19 is a smooth strain used as live vaccine against bovine
      brucellosis. Smooth lipopolysaccharide (LPS) is responsible for its residual
      virulence and serological interference. Rough mutants defective of LPS are more
      attenuated but confers lower level of protection. We describe a modified B.
      abortus S19 strain, named as S19Deltaper, which exhibits intermediate rough
      phenotype with residual O-polysaccharide (OPS). Deletion of perosamine synthetase
      gene resulted in substantial attenuation of S19Deltaper mutant without affecting
      immunogenic properties. It mounted strong immune response in Swiss albino mice
      and conferred protection similar to S19 vaccine. Immunized mice produced higher
      levels of IFN-gamma, IgG2a and thus has immune response inclined towards Th1 cell
      mediated immunity. Sera from immunized animals did not show agglutination
      reaction with RBPT antigen and thus could serve as DIVA (Differentiating Infected
      from Vaccinated Animals) vaccine. S19Deltaper mutant displayed more
      susceptibility to serum complement mediated killing and sensitivity to polymyxin
      B. Pregnant guinea pigs injected with S19Deltaper mutant completed full term of
      pregnancy and did not cause abortion, still birth or birth of weak offspring.
      S19Deltaper mutant with intermediate rough phenotype displayed remarkable
      resemblance to S19 vaccine strain with improved properties of safety,
      immunogenicity and DIVA capability for control of bovine brucellosis. 

PMID- 25869889
TI  - Developing vaccines to prevent sustained infection with Mycobacterium
      tuberculosis: Conference proceedings: National Institute of Allergy and
      Infectious Diseases, Rockville, Maryland USA, November 7, 2014.
AB  - On November 7, 2014, Aeras and the National Institute of Allergy and Infectious
      Diseases convened a conference entitled "Vaccine Prevention of Sustained
      Mycobacterium tuberculosis Infection." The purpose of this meeting was to explore
      the biologic plausibility, potential public health and economic impact, and
      regulatory feasibility in attempting to develop a vaccine to prevent sustained
      infection with Mycobacterium tuberculosis (Mtb). Currently there are two main
      goals for tuberculosis (TB) vaccine development, to develop a vaccine that could
      serve as a booster to Bacille Calmette-Guerin (BCG) vaccination and prevent
      active TB in adolescents and adults, and to develop an improved vaccine to
      replace BCG in infants. Although prevention of sustained Mtb infection is being
      used as a proof of biological activity for vaccines in mid-Phase 2 development,
      there currently are no plans for pursuing a prevention of Mtb infection licensure
      indication for TB vaccines. Ultimately, pursuing a prevention of sustained Mtb
      infection indication for TB vaccines, in parallel with ongoing efforts to develop
      vaccines to prevent active TB disease, was deemed a potentially important effort,
      but would require further resources, particularly to improve diagnostic assays,
      to increase the regulatory feasibility of this endeavor. 

PMID- 25869888
TI  - Internet activity as a proxy for vaccination compliance.
AB  - Tracking the progress of vaccination campaigns is a challenging and important
      public health need. Examining a recent Polio outbreak in the Middle East, we show
      that novel methods utilizing online search trends have great potential to provide
      a real-time, reliable proxy for vaccination rates over space and time. 

PMID- 25869890
TI  - Immunogenic virus-like particles continuously expressed in mammalian cells as a
      veterinary rabies vaccine candidate.
AB  - Rabies is one of the most lethal infectious diseases in the world, with a
      mortality approaching 100%. There are between 60,000 and 70,000 reported annual
      deaths, but this is probably an underestimation. Despite the fact that there are
      vaccines available for rabies, there is a real need of developing more
      efficacious and cheaper vaccines. This is particularly true for veterinary
      vaccines because dogs are still the main vector for rabies transmission to human
      beings. In a previous work, we described the development and characterization of
      rabies virus-like particles (RV-VLPs) expressed in HEK293 cells. We showed that
      RV-VLPs are able to induce a specific antibodies response. In this work, we show
      that VLPs are able to protect mice against virus challenge. Furthermore, we
      developed a VLPs expressing HEK-293 clone (sP2E5) that grows in serum free medium
      (SFM) reaching high cell densities. sP2E5 was cultured in perfusion mode in a 5 L
      bioreactor for 20 days, and the RV-VLPs produced were capable of triggering a
      protective immune response without the need of concentration or adjuvant
      addition. Further, these VLPs are able to induce the production of rabies virus
      neutralizing antibodies. These results demonstrate that RV-VLPs are a promising
      rabies vaccine candidate. 

PMID- 25869891
TI  - Long term effectiveness of adjuvanted influenza A(H1N1)pdm09 vaccine in children.
AB  - BACKGROUND: Immunological studies have indicated that the effectiveness of AS03
      adjuvanted monovalent influenza A(H1N1)pdm09 vaccine (Pandemrix) may be of longer
      duration than what is seen for non-adjuvanted seasonal influenza vaccines. Sixty
      nine percent of children 6 months-18 years of age in Stockholm County received at
      least one dose of Pandemrix during the 2009 pandemic. We studied the
      effectiveness of the vaccine during the influenza seasons 2010-2011 and 2012-2013
      in children hospitalized with virologically confirmed influenza. The season 2011
      2012 was not included, since influenza A(H3N2) was the predominant circulating
      strain. METHODS: In a retrospective case-control study using a modified test
      negative design we compared the percentage vaccinated with Pandemrix among
      children diagnosed with influenza A(H1N1)pdm09 (cases), with that of those
      diagnosed with influenza A(H3N2) or influenza B (controls) during the two
      seasons. We excluded children born after July 1, 2009, since only children who
      were 6 months of age or older received the pandemic vaccine in October-December
      2009. RESULTS: During the 2010-2011 season, 3/16 (19%) of children diagnosed with
      influenza A(H1N1)pdm09, vs. 32/41 (78%) of those with influenza A(H3N2) or
      influenza B had been vaccinated with Pandemrix in 2009. The odds ratio, after
      adjustment for sex, age and underlying diseases, for becoming a case when
      vaccinated with Pandemrix was 0.083 (95%CI 0.014, 0.36), corresponding to a VE of
      91.7%. During the season 2012-2013, there was no difference between the two
      groups; 59% of children diagnosed with influenza A(H3N2)/B and 60% of those with
      influenza A(H1N1)pdm09 had been vaccinated with Pandemrix in 2009. CONCLUSION:
      The AS03 adjuvanted monovalent influenza A(H1N1) pdm09 vaccine (Pandemrix) was
      effective in preventing hospital admission for influenza A(H1N1)pdm09 in children
      during at least two seasons.

PMID- 25869893
TI  - Final report on exposure during pregnancy from a pregnancy registry for
      quadrivalent human papillomavirus vaccine.
AB  - OBJECTIVE: To better describe the safety profile of pregnancy exposures to the
      qHPV vaccine by acquiring and analyzing post-marketing data on pregnancy
      outcomes. METHODS: This is a voluntary, post-marketing prenatal vaccine exposure
      registry. Enrollment criteria included an identifiable patient and health care
      provider from the United States, France, or Canada and exposure within 1 month
      before the date of onset of the last menstrual period or at any time during
      pregnancy. Outcomes of interest were pregnancy outcomes and birth defects.
      Prospectively reported cases were used for rate calculations. RESULTS: For the
      1752 prospective reports with known outcome, 1518 (86.6%) were live births,
      including ten twin pregnancies. Of 1527 neonates, 1444 (94.6%) had no congenital
      anomalies. The overall rate of spontaneous abortion was 6.7 per 100 outcomes (95%
      confidence interval [CI] 5.5-8.2). The prevalence of major birth defects was 2.4
      per 100 live-born neonates (95% CI 1.7-3.3). There were 12 fetal deaths (0.8 per
      100 outcomes, 95% CI 0.4-1.4). CONCLUSION: Rates of spontaneous abortions and
      major birth defects were not greater than the general population rates. Although
      no adverse signals have been identified to date, the qHPV vaccine is not
      recommended for use in pregnant women.

PMID- 25869892
TI  - Interim influenza vaccine effectiveness: A good proxy for final estimates in
      Spain in the seasons 2010-2014.
AB  - INTRODUCTION: The agreement between interim and final influenza vaccine
      effectiveness (VE) estimates would support the use of interim assessments as a
      proxy for final VE results to guide health authorities in influenza prevention.
      We aimed to compare interim/final VE estimates in Spain. METHODS: We used a test
      negative case-control study (cycEVA) for 2010/11-2013/14 seasons. Sensitivity
      analyses were carried out by type/subtype of influenza virus and by target groups
      for vaccination. RESULTS: In general, interim estimates were higher compared to
      end-season estimates. Interim and final VE differences were higher for the target
      groups compared to all population. Subtype-specific interim/final VE estimates
      showed greater concordance (3-13%) than for any virus (7-24%). CONCLUSION: In
      Spain, interim influenza VE estimates over 2010-2014 were a good proxy of the
      final protection of the vaccine. Interim and final estimates showed greater
      concordance for all population and if performed subtype-specific.

PMID- 25869894
TI  - Developing aerosol vaccines for Mycobacterium tuberculosis: Workshop proceedings:
      National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA,
      April 9, 2014.
AB  - On April 9, 2014, Aeras and the National Institute of Allergy and Infectious
      Diseases convened a workshop entitled "Developing Aerosol Vaccines for
      Mycobacterium tuberculosis" in Bethesda, MD. The purpose of the meeting was to
      explore the potential for developing aerosol vaccines capable of preventing
      infection with M. tuberculosis (Mtb), preventing the development of active
      tuberculosis (TB) among those latently infected with Mtb, or as immunotherapy for
      persons with active TB. The workshop was organized around four key questions
      relevant to developing and assessing aerosol TB vaccines: (1) What is the current
      knowledge about lung immune responses and early pathogenesis resulting after Mtb
      infection and what are the implications for aerosol TB vaccine strategies? (2)
      What are the technical issues surrounding aerosol vaccine delivery? (3) What is
      the current experience in aerosol TB vaccine development? and (4) What are the
      regulatory implications of developing aerosol vaccines, including those for TB?
      Lessons learned from the WHO effort to develop an aerosol measles vaccine served
      as a case example for overall discussions at the meeting. Workshop participants
      agreed that aerosol delivery represents a potentially important strategy in
      advancing TB vaccine development efforts. As no major regulatory, manufacturing
      or clinical impediments were identified, members of the workshop emphasized the
      need for greater support to further explore the potential for this delivery
      methodology, either alone or as an adjunct to traditional parenteral methods of
      vaccine administration. 

PMID- 25869895
TI  - Actions improving HPV vaccination uptake - Results from a national survey in
      Italy.
AB  - BACKGROUND: In Italy, HPV vaccination is offered to 11-year-old girls since 2007.
      In 2012 coverage was 69%. Strategies for offering and promoting HPV vaccination
      and coverage rates (26-85%) vary among Regions and Local Health Authorities
      (LHAs). We conducted a national study to identify strategies to improve HPV
      vaccination uptake. METHODS: In 2011-2012 we invited the 178 LHAs to fill a web
      questionnaire, inquiring implementation of HPV vaccination campaigns
      (immunization practices, logistics of vaccine delivery, training, activities to
      promote vaccination, barriers, local context). We described type of offer and
      vaccination promotion in each LHA and studied the association of these factors
      with vaccination coverage rates. RESULTS: We analyzed 133 questionnaires. The
      communication tools more frequently used to promote vaccination were:
      brochures/leaflets (92% of LHAs), fliers/posters (72%). Television (24%) and
      radio (15%) were less used. Using >=3 communication channels was associated to a
      coverage >=70% (ORadj=5.9, 95%CI 2.0-17.4). The probability to reach a coverage
      >=70% was higher if the invitation letter indicated a pre-assigned date for HPV
      vaccination (ORadj=7.0, 95%CI 1.2-39.8) and >1 recall for non-respondents was
      planned (ORadj=4.1, 95%CI 1.8-9.3). Immunization services and paediatricians were
      involved in informative and training activities in most LHAs (80-90%), instead
      general practitioners, women and family's healthcare services and public
      gynaecologists in 60-70%, cervical cancer screening services and private
      gynaecologists in 20-40%. The main factors that negatively affected vaccination
      uptake were: poor participation to training events of professional profiles
      different from personnel of immunization services (reported by 58% LHAs), their
      mistrust towards HPV vaccination (55%) and insufficient resources (56%).
      CONCLUSION: The synergy of multiple interventions is necessary for a successful
      vaccination programme. Practices such as pre-assigning vaccination date and
      repeatedly recalling non-respondents could improve vaccination uptake. Efforts
      are required to strengthen the training of different professional profiles and
      services and encourage their collaboration. Economical resources are needed to
      promote vaccination.

PMID- 25869897
TI  - Towards high quality triangular silver nanoprisms: improved synthesis, six-tip
      based hot spots and ultra-high local surface plasmon resonance sensitivity.
AB  - The great application potential of triangular silver nanoprisms (TSNPRs, also
      referred to as triangular silver nanoplates) is hampered by the lack of methods
      to produce well-defined tips with high monodispersity, with easily removable
      ligands. In this work, a simple one-step plasmon-mediated method was developed to
      prepare monodisperse high-quality TSNPRs. In this approach, the sole surface
      capping agent was the easily removable trisodium citrate. Differing from common
      strategies using complex polymers, OH(-) ions were used to improve the
      monodispersity of silver seeds, as well as to control the growth process through
      inhibiting the oxidation of silver nanoparticles. Using these monodisperse high
      quality TSNPRs as building blocks, self-assembled TSNPRs consisting of six-tip
      based "hot spots" were realized for the first time as demonstrated in a high
      enhancement (~10(7)) of surface-enhanced Raman scattering (SERS). From the
      plasmon band shift versus the refractive index, ultra-high local surface plasmon
      resonance sensitivity (413 nm RIU(-1) or 1.24 eV RIU(-1), figure of merit (FOM) =
      4.59) was reached at ~630 nm, making these materials promising for
      chemical/biological sensing applications. 

PMID- 25869896
TI  - Increased protective efficacy of recombinant BCG strains expressing virulence
      neutral proteins of the ESX-1 secretion system.
AB  - BACKGROUND: Mycobacterium bovis BCG is presently the only available anti
      tuberculosis vaccine used, worldwide. While BCG protects against miliary
      tuberculosis (TB) and tuberculoid meningitis in children, it often fails to
      protect against adult pulmonary TB. It is thus imperative that new improved anti
      TB vaccines are developed. The integration of the ESX-1 secretion system, absent
      from BCG due to the deletion of region of difference 1 (RD1), into the genome of
      BCG has been shown to confer to BCG::ESX-1 enhanced protection against TB as
      compared to BCG. METHODS: In the present study, to counterbalance the increase in
      virulence resulting from the integration of the RD1 region into BCG, we have
      constructed and evaluated several BCG::ESX-1 variants that carry selected amino
      acid changes in the ESX-1-secreted antigen ESAT-6. In order to find the candidate
      that combines low virulence with high protective efficacy, these novel
      recombinant BCG::ESX-1 strains were tested for their virulence properties and
      their protective efficacy against Mycobacterium tuberculosis in two different
      animal models (mouse and guinea-pig). RESULTS: Among several candidates tested,
      the BCG::ESAT-L28A/L29S strain, carrying modifications at residues Leu(28)
      Leu(29) of the ESAT molecule, showed strong attenuation in mice and high
      protective efficiency both in mouse and guinea-pig vaccination-infection models.
      CONCLUSION: This strain thus represents a promising candidate that merits further
      investigations and development. Our research also provides the proof of concept
      that selected ESX-1-complemented BCG strains may show low virulence and increased
      protective potential over parental strains.

PMID- 25869898
TI  - In-line positioning of ultrasound images using wireless remote display system
      with tablet computer facilitates ultrasound-guided radial artery catheterization.
AB  - Ultrasound-guided procedures may be easier to perform when the operator's eye
      axis, needle puncture site, and ultrasound image display form a straight line in
      the puncture direction. However, such methods have not been well tested in
      clinical settings because that arrangement is often impossible due to limited
      space in the operating room. We developed a wireless remote display system for
      ultrasound devices using a tablet computer (iPad Mini), which allows easy display
      of images at nearly any location chosen by the operator. We hypothesized that the
      in-line layout of ultrasound images provided by this system would allow for
      secure and quick catheterization of the radial artery. We enrolled first-year
      medical interns (n = 20) who had no prior experience with ultrasound-guided
      radial artery catheterization to perform that using a short-axis out-of-plane
      approach with two different methods. With the conventional method, only the
      ultrasound machine placed at the side of the head of the patient across the
      targeted forearm was utilized. With the tablet method, the ultrasound images were
      displayed on an iPad Mini positioned on the arm in alignment with the operator's
      eye axis and needle puncture direction. The success rate and time required for
      catheterization were compared between the two methods. Success rate was
      significantly higher (100 vs. 70 %, P = 0.02) and catheterization time
      significantly shorter (28.5 +/- 7.5 vs. 68.2 +/- 14.3 s, P < 0.001) with the
      tablet method as compared to the conventional method. An ergonomic straight
      arrangement of the image display is crucial for successful and quick completion
      of ultrasound-guided arterial catheterization. The present remote display system
      is a practical method for providing such an arrangement. 

PMID- 25869899
TI  - A multi-channel acoustics monitor for perioperative respiratory monitoring:
      preliminary data.
AB  - This study pertains to a six-channel acoustic monitoring system for use in
      patient monitoring during or after surgery. The base hardware consists of a USB
      data acquisition system, a custom-built six-channel amplification system, and a
      series of microphones of various designs. The software is based on the MATLAB
      platform with data acquisition drivers installed. The displayed information
      includes: time domain signals, frequency domain signals, and tools to aid in the
      detection of endobronchial intubation. We hypothesize that the above mentioned
      arrangement may be helpful to the anesthesiologist in recognizing clinical
      conditions like wheezing, bronchospasm, endobronchial intubation, and apnea. The
      study also evaluated various types of microphone designs used to transduce breath
      sounds. The system also features selectable band-pass filtering using MATLAB
      algorithms as well as a collection of recordings obtained with the system to
      establish what respiratory acoustic signals look like under various conditions. 

PMID- 25869901
TI  - Eating disorders in men aged midlife and beyond.
AB  - Eating disorders are serious psychiatric illnesses which can occur across the
      lifespan. Men aged midlife and beyond are vulnerable to stigma, shame, and
      stereotypes portraying eating disorders as afflictions of youth and female
      gender. Historically, men have been neglected in the field of eating disorders
      owing to traditional and female-centric approaches to conceptualization and
      classification. In this literature review, we identified 16 case reports of
      eating disorders in males ranging from the age of 40 to 81 years. The majority of
      cases reported an earlier onset in life, followed by a variable course of illness
      with periods of relapse interspersed with remission. Diagnostic crossover or
      symptom fluctuation was common. High rates of comorbid depression were found, and
      several cases described a history of weight cycling and premorbid obesity.
      Precipitating factors included stressors which disproportionately occur in later
      life, including loss due to death or divorce, changes in financial or housing
      situation, and medical issues. Very little is known regarding the prevalence of
      eating disorders in older men, with initial population estimates ranging from
      0.02% to 1.6%. Rates of subthreshold eating disordered behavior are higher and
      appear to be increasing among older individuals and males in the community.
      Recent revisions in the DSM-5 will likely increase the broader applicability of
      diagnostic criteria for eating disorders, stimulating improved recognition of
      diverse presentations occurring across the lifespan for both genders. Eating
      disorders should be included in the differential diagnosis of unexplained weight
      gain or weight loss irrespective of age or gender. Multi-site studies are needed
      for adequate sampling and to allow larger empirical investigations regarding how
      to improve clinical practices in screening and assessment, as well the provision
      of differential care for older men suffering from an eating disorder. 

PMID- 25869900
TI  - Adjustment in the clinical practice of treat-to-target guidelines for rheumatoid
      arthritis: Results of the ToARCan study.
AB  - OBJECTIVE: To analyze compliance with t2t clinical practice guidelines. METHODS:
      Cross-sectional observational study in consecutive patients with rheumatoid
      arthritis (RA) in 5 hospitals in the Canary Islands. Patients filled out activity
      scales, HAQ and answered the question of whether the doctor had explained the
      treatment target. The rheumatologist also collected: visits in the past year, use
      of activity indices and HAQ, DAS28 of current visit and date of the next visit.
      The percentage of compliance to indicators based on the t2t recommendations (R)
      1, 3, 5-7 and 10 was analyzed. RESULTS: A total of 343 patients were recruited,
      77% female, mean age 57, RA duration of 10 years. Median visits in the last year
      were 3 and mean time between last and current visit was 5.6 months. A total of
      93% of the patients were treated with DMARDs and 44% were in remission by DAS
      (R1). In the previous visit, documented joint count was present in 85%, a HAQ in
      19%, patient VAS in 41%, and a DAS28 in 35% of the patients (R6). The next visit
      was scheduled at an average of 4.3 months (R5). In 64% of patients with DAS28>
      3.2 a visit between one and 3 months was scheduled (R5). A total of 96% of
      patients said they had been informed of the treatment target (R10). Variability
      between centers existed but was moderate. The only factor determining the
      performance of a DAS28 in the last visit was the patient's center of origin.
      CONCLUSIONS: The Canary Island centers studied achieved high levels of remission
      and low activity in their patients. The performance of composite indices and
      follow-up frequency recommended by the t2t are met, although there is room for
      improvement.

PMID- 25869902
TI  - Subclinical cardiovascular disease in postmenopausal women with low/medium
      cardiovascular risk by the Framingham risk score.
AB  - OBJECTIVES: To evaluate the prevalence of subclinical cardiovascular disease
      (CVD) and its association with clinical and hormone variables in postmenopausal
      women from Southern Brazil. STUDY DESIGN: Cross-sectional study. MAIN OUTCOME
      MEASURES: Coronary artery calcification (CAC) assessed by electron-beam computed
      tomography. Carotid intima-media thickness (IMT) and atheromatous plaques
      assessed using B-mode ultrasound. IMT was measured at three segments. Subclinical
      CVD was defined as the presence of plaque and/or IMT >0.9 mm. RESULTS: Ninety
      seven postmenopausal women (mean age 55 +/- 5 years, median duration of menopause
      5.8 [3-10] years) were studied. A low/medium Framingham risk score (FRS) was
      present in 97.9% of participants; 35.1% had subclinical CVD on carotid
      ultrasound, and 24.7% had the presence of plaque. Seven women had a CAC score >=
      100, and two had a score >= 200. CAC score (p<0.001) and FRS (p=0.013) were
      higher in patients with subclinical atherosclerosis. Positive correlations were
      found between IMT and age (rs=0.293 p=0.004), duration of menopause (rs=0.237,
      p=0.020), and CAC score (rs=0.468, p<0.001). Common carotid IMT (IMT-CC) was
      negatively associated with estradiol levels (beta=-0.237, p=0.018) and positively
      with age (beta=0.210, p=0.033), and BMI (beta=0.260, p=0.010). However,
      correlations with estradiol and age did not remain significant when adjusted for
      systolic blood pressure and LDL-cholesterol levels. CONCLUSION: A high prevalence
      of subclinical atherosclerosis was detected in this sample of postmenopausal
      women with low/medium CV risk by the FRS. The association between IMT-CC and age
      or endogenous estrogen levels was dependent of blood pressure and LDL-cholesterol
      in these postmenopausal women from Southern Brazil.

PMID- 25869903
TI  - Impact of depression and anxiety on adverse event profiles in Korean people with
      epilepsy.
AB  - Previous studies have shown that depression and anxiety worsen the adverse events
      associated with antiepileptic drugs (AEDs) in people with epilepsy. These studies
      used the Liverpool Adverse Events Profile (LAEP) to screen adverse events. The
      LAEP incorporates items associated with emotion, which may themselves influence
      the reporting of adverse events. We investigated whether depression and anxiety
      still displayed an effect on adverse events when items related to emotion were
      excluded from the analysis. A total of 453 consecutive patients with epilepsy who
      took AEDs for at least 1year completed self-report questionnaires, including the
      Korean versions of the LAEP (K-LAEP), the Beck Depression Inventory (K-BDI), and
      the Beck Anxiety Inventory (K-BAI). Firstly, we performed a discrimination
      analysis to identify the items affected by depression and/or anxiety among the 19
      items included in the K-LAEP. Among these items, dizziness, nervousness and/or
      agitation, restlessness, and upset stomach had relatively higher levels of
      significance. Secondly, we performed a factor analysis to determine the subclass
      taxonomy of all items in the K-LAEP. The analysis segregated the items into three
      subclasses: cephalgia/coordination/sleep, emotion/cognition, and
      tegument/mucosa/weight. Lastly, we performed stepwise multiple regressions to
      demonstrate the predictors determining the K-LAEP and subclass scores. According
      to the regressions, the K-BAI and K-BDI scores and the duration of treatment of
      the antiepileptic medication were significant predictors. Specifically, the K-BAI
      score was a predictor of the scores of all three subclasses as well as the total
      K-LAEP score; the K-BDI score was a predictor of the total K-LAEP score and the
      emotion/cognition score; and the duration of treatment of the antiepileptic
      medication was a predictor of the tegument/mucosa/weight score. The K-BAI score
      was the strongest predictor of all the scores. Although this study showed a
      similar impact of depression and anxiety on the adverse event profiles as
      previous reports, it provided further insight into the contribution of the LAEP
      items associated with emotion. Other than the psychosocial predictors, the
      treatment duration of the antiepileptic medication was also found to be an
      important predictor in this study. 

PMID- 25869904
TI  - Pharmacokinetic characterization of BMS-936561, an anti-CD70 antibody-drug
      conjugate, in preclinical animal species and prediction of its pharmacokinetics
      in humans.
AB  - CD70 is a tumor necrosis factor (TNF)-like type II integral membrane protein that
      is transiently expressed on activated T- and B-lymphocytes. Aberrant expression
      of CD70 was identified in both solid tumors and haematologic malignancies. BMS
      936561 (alphaCD70_MED-A) is an antibody-drug conjugate composed of a fully human
      anti-CD70 monoclonal antibody (alphaCD70) conjugated with a duocarmycin
      derivative, MED-A, through a maleimide-containing citrulline-valine dipeptide
      linker. MED-A is a carbamate prodrug that is activated by carboxylesterase to its
      active form, MED-B, to exert its DNA alkylation activity. In vitro serum
      stability studies suggested the efficiencies of hydrolyzing the carbamate
      protecting group in alphaCD70_MED-A followed a rank order of mouse>rat >
      >monkey>dog~human. Pharmacokinetics of alphaCD70_MED-A was evaluated in mice,
      monkeys, and dogs after single intravenous doses. In mice, alphaCD70_MED-A was
      cleared rapidly, with no detectable exposures after 15 min following dosing. In
      contrast, alphaCD70_MED-A was much more stable in monkeys and dogs. The clearance
      of alphaCD70_MED-A in monkeys was 58 mL/d/kg, ~2-fold faster than that in dogs
      (31 mL/d/kg). The human PK profiles of the total alphaCD70 and alphaCD70_MED-A
      were predicted using allometrically scaled monkeys PK parameters of alphaCD70 and
      the carbamate hydrolysis rate constant estimated in dogs. Comparing the predicted
      and observed human PK from the phase I study, the dose-normalized concentration
      time profiles of alphaCD70_MED-A and the total alphaCD70 were largely within the
      5(th)-95(th) percentile of the predicted profiles.

PMID- 25869905
TI  - Appropriate nomenclature: angiotensin II receptors.

PMID- 25869906
TI  - Erratum to: Arthroscopic reconstruction of the popliteus complex: accuracy and
      reproducibility of a new surgical technique.

PMID- 25869907
TI  - The relationship between quadriceps strength and joint position sense, functional
      outcome and painful activities in patellofemoral pain syndrome.
AB  - PURPOSE: The aim of this study was to investigate how strongly the concentric and
      eccentric quadriceps strengths were correlated with the joint position sense,
      functional outcomes and painful activities in patients with patellofemoral pain
      syndrome (PFPS). METHODS: The study included forty-six women diagnosed with
      unilateral PFPS. Eccentric and concentric quadriceps strengths were recorded at
      60 and 180 degrees /s. Active knee joint position sense (JPS) was measured at 20
      degrees  and 60 degrees  of flexion. Functional levels were determined by using
      Kujala patellofemoral scores. Pain levels during stair descending and ascending,
      squatting and prolonged sitting were measured using 0-10 cm visual analogue
      scale. The relationship of isokinetic quadriceps strength with JPS results,
      Kujala score and pain levels were evaluated using Spearman's correlation
      coefficient test. RESULTS: Eccentric and concentric quadriceps strengths were
      significantly lower on involved side than uninvolved side. JPS results were
      poorer on the painful knee when compared to uninvolved side. While eccentric
      strength correlated with both JPS target angles, concentric strength was
      correlated only with 20 degrees . Both eccentric and concentric strengths were
      significantly correlated with Kujala scores and pain levels. CONCLUSION:
      Quadriceps eccentric strength was correlated more to joint position sense than
      concentric strength. Both eccentric and concentric quadriceps strength related to
      pain and functional level in PFPS patients.

PMID- 25869908
TI  - Return to sports after ACL reconstruction: individual considerations.

PMID- 25869909
TI  - Pulmonary Hypertension and Noncardiac Surgery: Implications for the
      Anesthesiologist--Additional Considerations.

PMID- 25869910
TI  - [Mild therapeutic hypothermia: Improved survival after resuscitation].
AB  - BACKGROUND: The favorable effect of mild therapeutic hypothermia (MTH) on
      neurologic status as well as on overall survival was shown in several trials;
      however, MTH is not readily implemented in daily routine. OBJECTIVE: We examined
      the effect of the implementation of MTH on neurologic outcome and overall
      survival in an emergency care hospital. STUDY DESIGN AND METHODS: The data of 68
      patients between 09/2010 and 11/2011 who received MTH for 24 h at 33  degrees C
      after cardiopulmonary resuscitation (CPR) were compared with prospectively
      collected data from 180 patients before introduction of MTH (2001-2006). Survival
      and neurological status at discharge were determined using the Glasgow-Pittsburgh
      Cerebral Performance Categories (CPC). RESULTS: MTH raised the percentage of
      patients with a CPC score of 1 or 2 from 70 % to 85 %. Furthermore, survival
      increased from 47/180 (26 %) between 01/2000 and 01/2006 to 27/68 (40 %) between
      09/2010 and 11/2011. DISCUSSION: Implementation of MTH leads to improved
      neurological status and overall survival after CPR.

PMID- 25869911
TI  - A Collaborative Assembly Strategy for Tumor-Targeted siRNA Delivery.
AB  - A novel "collaborative assembly" approach was reported for the synthesis of an
      siRNA delivery system via a combination of an electrostatically driven physical
      assembly and a facile click reaction-mediated chemical assembly, which showed
      various advantages of more safety, efficiency, and flexibility over the
      conventional approach that is only based on the physical assembly. This strategy
      remained a high cationic property of lipid-based complex for high siRNA loading
      capacity. The direct chemical modification of a model polyanion, hyaluronic acid
      (HA) on the cationic complex via click chemistry shielded the positive charge of
      complex without affecting the siRNA binding, which reduced the toxicity and
      enhanced the blood stability of the complex. In addition, the incorporated
      polyanion might be prefunctionalized, which endued the carrier with better
      biological characteristics such as long circulating or tumor targeting. We
      demonstrated that the obtained lipid-polymer hybrid nanoparticle (RSC-HA) using
      collaborative assembly presented greater in vivo stability in the blood for
      efficient tumor targeting than the physically assembled RSC/HA in which HA was
      physically adsorbed on the complex. After endocytosis into the cells, the
      protection of RSC-HA on siRNA turned off, while the release of siRNA induced by
      the intracellular signals for enhanced gene-silencing capacity. This combination
      of physical and chemical assemblies provides an efficient strategy for the
      exploitation of safe, stable, and functionalized siRNA delivery systems. 

PMID- 25869912
TI  - Risk Factors for Recurrence of Carbapenem-Resistant Enterobacteriaceae Carriage:
      Case-Control Study.
AB  - BACKGROUND: The natural history of carbapenem-resistant Enterobacteriaceae (CRE)
      carriage and the timing and procedures required to safely presume a CRE-free
      status are unclear. OBJECTIVE: To determine risk factors for recurrence of CRE
      among presumed CRE-free patients. METHODS: Case-control study including CRE
      carriers in whom CRE carriage presumably ended, following at least 2 negative
      screening samples on separate days. Recurrence of CRE carriage was identified
      through clinical samples and repeated rectal screening in subsequent admissions
      to any healthcare facility in Israel. Patients with CRE recurrence (cases) were
      compared with recurrence-free patients (controls). The duration of follow-up was
      1 year for all surviving patients. RESULTS: Included were 276 prior CRE carriers
      who were declared CRE-free. Thirty-six persons (13%) experienced recurrence of
      CRE carriage within a year after presumed eradication. Factors significantly
      associated with CRE recurrence on multivariable analysis were the time in months
      between the last positive CRE sample and presumed eradication (odds ratio, 0.94
      [95% CI, 0.89-0.99] per month), presence of foreign bodies at the time of
      presumed eradication (4.6 [1.64-12.85]), and recurrent admissions to healthcare
      facilities during follow-up (3.15 [1.05-9.47]). The rate of CRE recurrence was
      25% (11/44) when the carrier status was presumed to be eradicated 6 months after
      the last known CRE-positive sample, compared with 7.5% (10/134) if presumed to be
      eradicated after 1 year. CONCLUSIONS: We suggest that the CRE-carrier status be
      maintained for at least 1 year following the last positive sample. Screening of
      all prior CRE carriers regardless of current carriage status is advised.

PMID- 25869913
TI  - Paediatric gastroenterology. On a knife-edge--weight-loss surgery for NAFLD in
      adolescents.
AB  - A new position statement from Europe endorses expert-based recommendations to
      consider bariatric surgery as a treatment for severe NAFLD in severely obese
      adolescents. This article discusses the problem of severe paediatric obesity, its
      relationship with NAFLD, and the knowledge and needs regarding bariatric surgery
      in adolescents

PMID- 25869914
TI  - Bariatric surgery: To bypass or switch? That is the question in obesity surgery.

PMID- 25869915
TI  - Pharmacokinetics and dosing estimation of meropenem in Japanese patients
      receiving continuous venovenous hemodialysis.
AB  - The pharmacokinetics of meropenem have not yet been examined in Japanese patients
      receiving Continuous venovenous hemodialysis (CVVHD). The aim of this clinical
      investigation was to determine the pharmacokinetic parameters of meropenem in
      critically ill patients receiving CVVHD in order to estimate dosing regimens for
      the patient population in Japan. The values of pharmacokinetic parameters were
      17.5 +/- 5.6 l for V1, 1.27 +/- 0.38 h(-1) for K12, 0.71 +/- 0.40 h(-1) for K21
      and 0.17 +/- 0.02 h(-1) for K10. Based on these mean parameters (V1, K12, K21 and
      K10), time above MIC (T > MIC) values were estimated at different MICs using
      various meropenem regimens. For bacteria with a meropenem MIC of <= 2 MUg/ml, a
      dosing regimen of 0.25 g every 24 h achieved more than 40% T > MIC. For a MIC of
      4 MUg/ml, all the regimens tested, except for 0.25 g every 24 h, achieved more
      than 40% T > MIC. For a MIC of 16 MUg/ml, dosing regimens of 0.5 g every 8 h, 1 g
      every 12 h, and 1 g every 8 h achieved 40% T > MIC, reaching the pharmacokinetic
      pharmacodynamic target range. This is the first study to examine the
      pharmacokinetics of meropenem under a CVVHD setting in Japan. The pharmacokinetic
      pharmacodynamic profile of dosing regimens tested in this study will assist in
      selecting the appropriate meropenem regimens for patients receiving CVVHD.

PMID- 25869916
TI  - Comparison of the pathogenesis of single or dual infections with type 1 and type
      2 porcine reproductive and respiratory syndrome virus.
AB  - The aim of this study was to compare the pathogenicity of single or dual
      infections with type 1 and type 2 porcine reproductive and respiratory syndrome
      virus (PRRSV) in pigs. Pigs were inoculated intranasally with type 1 or type 2
      PRRSV or both viruses together. Pigs infected with type 1 and type 2 PRRSV
      together had significantly (P <0.05) fewer genomic copies of type 1 PRRSV than
      did pigs infected with type 1 PRRSV alone. Pigs infected with type 2 PRRSV alone
      or type 1 and type 2 PRRSV together had significantly (P <0.05) higher gross and
      microscopical lung lesion scores than did pigs infected with type 1 PRRSV alone.
      Pigs infected with type 2 PRRSV alone or type 1 and type 2 PRRSV together had
      significantly (P <0.05) higher scores for PRRSV-positive cells in the lung than
      did pigs infected with type 1 PRRSV alone. Pigs infected with type 1 PRRSV alone
      had significantly (P <0.05) higher scores for type 1 PRRSV-positive cells in the
      lung than did pigs infected with both types of PRRSV together. Pigs infected with
      both types of PRRSV together developed similar clinical disease and lesions as
      pigs infected with type 2 PRRSV alone. Significant differences in virulence were
      not observed between pigs infected with type 2 PRRSV alone and pigs infected with
      both types of PRRSV together in terms of viraemia, lung lesion score and virus
      distribution within lung lesions. 

PMID- 25869917
TI  - Pre-clinical activity of PR-104 as monotherapy and in combination with sorafenib
      in hepatocellular carcinoma.
AB  - PR-104 is a clinical stage bioreductive prodrug that is converted in vivo to its
      cognate alcohol, PR-104A. This dinitrobenzamide mustard is reduced to activated
      DNA cross-linking metabolites (hydroxylamine PR-104H and amine PR-104M) under
      hypoxia by one-electron reductases and independently of hypoxia by the 2-electron
      reductase aldo-keto reductase 1C3 (AKR1C3). High expression of AKR1C3, along with
      extensive hypoxia, suggested the potential of PR-104 for treatment of
      hepatocellular carcinoma (HCC). However, a phase IB trial with sorafenib
      demonstrated significant toxicity that was ascribed in part to reduced PR-104A
      clearance, likely reflecting compromised glucuronidation in patients with
      advanced HCC. Here, we evaluate the activity of PR-104 in HCC xenografts (HepG2,
      PLC/PRF/5, SNU-398, Hep3B) in mice, which do not significantly glucuronidate PR
      104A. Cell line differences in sensitivity to PR-104A in vitro under aerobic
      conditions could be accounted for by differences in both expression of AKR1C3
      (high in HepG2 and PLC/PRF/5) and sensitivity to the major active metabolite PR
      104H, to which PLC/PRF/5 was relatively resistant, while hypoxic selectivity of
      PR-104A cytotoxicity and reductive metabolism was greatest in the low-AKR1C3 SNU
      398 and Hep3B lines. Expression of AKR1C3 in HepG2 and PLC/PRF/5 xenografts was
      in the range seen in 21 human HCC specimens. PR-104 monotherapy elicited
      significant reductions in growth of Hep3B and HepG2 xenografts, and the
      combination with sorafenib was significantly active in all 4 xenograft models.
      The results suggest that better-tolerated analogs of PR-104, without a
      glucuronidation liability, may have the potential to exploit AKR1C3 and/or
      hypoxia in HCC in humans. 

PMID- 25869918
TI  - In vitro and in vivo Bone-Forming Activity of Saururus chinensis Extract.
AB  - Bone is maintained by osteoclast-mediated resorption and osteoblast-mediated
      formation. Recently, anti-osteoporotic activity of Saururus chinensis extract
      (SCE) and anti-osteoclastogenic activity of its components have been reported,
      but the effect of SCE on bone formation has not been studied well. Therefore, in
      this study, we investigated whether Saururus chinensis SCE exhibits in vitro
      osteogenic and in vivo bone-forming activity. extract strongly enhanced the bone
      morphogenetic protein (BMP)-2-stimulated induction of alkaline phosphatase, an
      early phase biomarker of osteoblast differentiation, in bi-potential mesenchymal
      progenitor C2C12 cells. In vitro osteogenic activity of SCE was accompanied by
      enhanced expression of BMP-2, BMP-4, BMP-7 and BMP-9 mRNA. In addition, a
      pharmacological inhibition study suggested the involvement of p38 activation in
      the osteogenic action of SCE. Moreover, the BMP dependency and the involvement of
      p38 activation in the osteogenic action of SCE were confirmed by the treatment of
      noggin, an antagonist of BMP. Saururus chinensis extract also exhibited to induce
      runt-related transcription factor 2 activation at the high concentration.
      Furthermore, the in vivo osteogenic activity of SCE was confirmed in zebrafish
      and mouse calvarial bone formation models, suggesting the possibility of its use
      for bone formation. In conclusion, we suggested that in vivo anti-osteoporotic
      activity of SCE could be because of its dual action in bone, anti
      osteoclastogenic and anabolic activity.

PMID- 25869919
TI  - Prevalence of fear of falling in older adults, and its associations with
      clinical, functional and psychosocial factors: the Frailty in Brazilian Older
      People-Rio de Janeiro study.
AB  - AIM: The present study estimated the prevalence of fear of falling in older
      adults, and its associations with clinical, functional and psychosocial factors.
      METHODS: Data from the Research Network Frailty in Brazilian Older People,
      specifically the Rio de Janeiro Study involving participants aged 65 years and
      older residing in the city of Rio de Janeiro, Brazil, were analyzed. Fear of
      falling was assessed by the Brazilian version of Falls Efficacy Scale
      International. The following variables were assessed: history of falls, fracture
      after fall, number of comorbidities, number of medications, hospitalization in
      the previous year, use of walking support device, functional dependency in
      activities of daily living (including instrumental activities), hearing and
      visual impairments, hand grip strength, walking speed, self-rated health,
      depressive symptoms, cognitive impairment, living alone, social support, and
      activity level. Associations were evaluated by multiple logistic regression.
      RESULTS: Among the 742 participants, 51.9% had a fear of falling, which was more
      prevalent in women and older participants. Fear of falling was associated with a
      history of one to two falls (odds ratio [OR] 2.18; 95% confidence interval [CI]
      1.42-3.36), three or more falls (OR 2.72, 95% CI 1.10-6.70), use of seven or more
      medications (OR 1.70, 95%CI 1.04-2.80), hearing impairment (OR 1.66, 95% CI 1.10
      2.49), functional dependence in activities of daily living (OR 1.73, 95% CI 1.07
      2.79), diminished gait speed (OR 1.64 95% CI 1.04-2.58), fair self-rated health
      (OR 1.89, 95% CI, 1.30-2.74), poor/very poor self-rated health (OR 4.92, 95% CI
      1.49-16.27) and depressive symptoms (OR 1.68, 95% CI 1.07-2.63). CONCLUSIONS: The
      prevalence of fear of falling was high in this population, and was associated
      with history of falls, use of seven or more medications, hearing impairment,
      functional dependency in activities of daily living, diminished walking speed,
      fair and poor/very poor self-rated health and depressive symptoms.

PMID- 25869920
TI  - Pneumonia associated with Acinetobacter baumannii in a group of minks (Neovison
      vison).

PMID- 25869922
TI  - Long Acting Intranasal Insulin Detemir Improves Cognition for Adults with Mild
      Cognitive Impairment or Early-Stage Alzheimer's Disease Dementia.

PMID- 25869921
TI  - Development and evaluation of near-isogenic lines for major blast resistance
      gene(s) in Basmati rice.
AB  - KEY MESSAGE: A set of NILs carrying major blast resistance genes in a Basmati
      rice variety has been developed. Also, the efficacy of pyramids over monogenic
      NILs against rice blast pathogen Magnaporthe oryzae has been demonstrated.
      Productivity and quality of Basmati rice is severely affected by rice blast
      disease. Major genes and QTLs conferring resistance to blast have been reported
      only in non-Basmati rice germplasm. Here, we report incorporation of seven blast
      resistance genes from the donor lines DHMASQ164-2a (Pi54, Pi1, Pita), IRBLz5-CA
      (Pi2), IRBLb-B (Pib), IRBL5-M (Pi5) and IRBL9-W (Pi9) into the genetic background
      of an elite Basmati rice variety Pusa Basmati 1 (PB1). A total of 36 near
      isogenic lines (NILs) comprising of 14 monogenic, 16 two-gene pyramids and six
      three-gene pyramids were developed through marker-assisted backcross breeding
      (MABB). Foreground, recombinant and background selection was used to identify the
      plants with target gene(s), minimize the linkage drag and increase the recurrent
      parent genome (RPG) recovery (93.5-98.6 %), respectively, in the NILs.
      Comparative analysis performed using 50,051 SNPs and 500 SSR markers revealed
      that the SNPs provided better insight into the RPG recovery. Most of the
      monogenic NILs showed comparable performance in yield and quality, concomitantly,
      Pusa1637-18-7-6-20 (Pi9), was significantly superior in yield and stable across
      four different environments as compared to recurrent parent (RP) PB1. Further,
      among the pyramids, Pusa1930-12-6 (Pi2+Pi5) showed significantly higher yield and
      Pusa1633-7-8-53-6-8 (Pi54+Pi1+Pita) was superior in cooking quality as compared
      to RP PB1. The NILs carrying gene Pi9 were found to be the most effective against
      the concoction of virulent races predominant in the hotspot locations for blast
      disease. Conversely, when analyzed under artificial inoculation, three-gene
      pyramids expressed enhanced resistance as compared to the two-gene and monogenic
      NILs.

PMID- 25869925
TI  - Functional Liver Recovery After Bariatric Surgery--a Prospective Cohort Study
      with the LiMAx Test.
AB  - BACKGROUND: Bariatric surgery provides long-term weight loss and improvement of
      obesity-associated diseases such as nonalcoholic steatohepatitis (NASH).
      Histologic improvement of NASH has been reported in some studies after bariatric
      surgery. This study was designed to assess the liver function in obese patients
      as well as its recovery after bariatric surgery with a noninvasive test method.
      METHODS: In a prospective cohort study from October 2011 to May 2014, morbidly
      obese individuals receiving bariatric surgery were investigated for functional
      liver recovery (n = 34). Liver function was determined by the LiMAx test
      (enzymatic capacity of cytochrome P450 1A2) preoperatively, 6 and 12 months
      postoperatively. Liver biopsy specimens were obtained from 18 participants and
      classified according to the nonalcoholic fatty liver disease (NAFLD) activity
      score (NAS). RESULTS: The mean age of participants was 44 years, and the mean
      body mass index (BMI) was 52 kg/m(2). The mean percent excess BMI loss (%EBMIL)
      was 53 % after 6 months and 68 % after 1 year. Mean liver function capacity
      increased significantly from 255 MUg/kg/h preoperative to 324 MUg/kg/h after 6
      months and 342 MUg/kg/h after 12 months. A negative correlation was observed
      between %EBMIL and alteration of liver function capacity in the first 6 months.
      Finally, the median NAS showed a negative correlation with liver function
      capacity. CONCLUSIONS: Bariatric surgery leads to a significant functional
      recovery of the liver. An initial marked weight loss may negatively influence
      functional liver recovery.

PMID- 25869926
TI  - ATXN3, ATXN7, CACNA1A, and RAI1 Genes and Mitochondrial Polymorphism A10398G Did
      Not Modify Age at Onset in Spinocerebellar Ataxia Type 2 Patients from South
      America.

PMID- 25869927
TI  - High Serum GFAP Levels in SCA3/MJD May Not Correlate with Disease Progression.
AB  - Spinocerebellar ataxia type 3(SCA3), also known as Machado-Joseph disease (MJD),
      is the most frequent subtype of autosomal dominant inherited spinocerebellar
      ataxias, which caused by the expansion of CAG repeats in the ATXN3 gene. The
      number of CAG repeats of the abnormal allele determines the rate of disease
      progression in patients with SCA3/MJD. Markers to assess the clinical severity,
      to predict the course of illness and to monitor the efficacy of therapeutic
      measures, can be clinical, biological, and radiological. Here, we aimed to
      explore whether the serum glial fibrillary acidic protein (GFAP) may act as a
      biomarker in SCA3/MJD patients and to evaluate the correlation between some
      markers with the number of CAG repeats in SCA3/MJD patients. We showed that the
      serum levels of GFAP were significantly higher in SCA3/MJD patients than in
      controls. There was a strong positive correlation between the age-adjusted GFAP
      levels with the number of CAG repeats. Age-adjusted International Cooperative
      Ataxia Rating Scale (ICARS) scores and Scale for the Assessment and Rating of
      Ataxia (SARA) scores correlated with the number of CAG repeats. Raw scores and
      disease duration-adjusted GFAP levels, ICARS scores, and SARA scores were not
      correlated with the number of CAG repeats. Our results reveal novel evidence for
      the role of the triplet expansion in SCA3/MJD-associated neuronal damage. 

PMID- 25869928
TI  - Loss of PCDH9 is associated with the differentiation of tumor cells and
      metastasis and predicts poor survival in gastric cancer.
AB  - Microarray studies revealed down-regulation of PCDH9 mRNA level in lymph node
      metastasis of gastric cancer compared with the primary tumors. The expression of
      PCDH9 protein and its clinicopathological relevance were assessed on tissue
      microarrays of 1072 cases of gastric cancer. Its prognostic value was further
      evaluated on a small cohort of 175 gastric cancers. PCDH9 was down-regulated
      during the development and progression of gastric cancer. The overall rates of
      PCDH9 expression in normal, primary tumor, nodal and hepatic metastatic tissues
      were 100 % (1072/1072), 48.0 % (515/1072), 20.1 % (34/169), and 5.6 % (1/18),
      respectively. Positive staining of PCDH9 protein was significantly reversely
      correlated with tumor size, tumor differentiation, tumor invasion, lymph node
      metastasis, and disease progression. The Cox proportional hazards model revealed
      that the PCDH9 was an independent prognostic factor for gastric cancer.
      Therefore, decreased expression of PCDH9 is frequent in human gastric cancer
      metastasis and PCDH9 expression is an independent prognostic factor, suggesting
      that PCDH9 could be a promising biomarker of this malignancy.

PMID- 25869929
TI  - Residual hemifacial spasm after microvascular decompression: prognostic factors
      with emphasis on preoperative psychological state.
AB  - Residual hemifacial spasm (HFS) after microvascular decompression (MVD) is
      common, and the factors associated with residual HFS are still controversial. In
      the present study, we analyzed the outcome of 212 patients with hemifacial spasm
      after a single microvascular decompression and evaluated the prognostic factors
      involved in residual hemifacial spasm. Based on our study, possible prognostic
      factors included indentation of the root exit zone (REZ), preoperative illness
      duration, and preoperative psychological state. We suggest that MVD should be
      performed as early as possible for it may decrease the rate of residual HFS.
      Preoperative assessment of psychological state in HFS patients is a timely
      intervention that should be implemented to minimize the residual HFS. 

PMID- 25869930
TI  - Self-regulation of breathing as a primary treatment for anxiety.
AB  - Understanding the autonomic nervous system and homeostatic changes associated
      with emotions remains a major challenge for neuroscientists and a fundamental
      prerequisite to treat anxiety, stress, and emotional disorders. Based on recent
      publications, the inter-relationship between respiration and emotions and the
      influence of respiration on autonomic changes, and subsequent widespread membrane
      potential changes resulting from changes in homeostasis are discussed. We
      hypothesize that reversing homeostatic alterations with meditation and breathing
      techniques rather than targeting neurotransmitters with medication may be a
      superior method to address the whole body changes that occur in stress, anxiety,
      and depression. Detrimental effects of stress, negative emotions, and sympathetic
      dominance of the autonomic nervous system have been shown to be counteracted by
      different forms of meditation, relaxation, and breathing techniques. We propose
      that these breathing techniques could be used as first-line and supplemental
      treatments for stress, anxiety, depression, and some emotional disorders. 

PMID- 25869932
TI  - Evidence for the conservation of miR-223 in zebrafish (Danio rerio): Implications
      for function.
AB  - MicroRNAs (miRNAs) are an abundant and conserved class of small RNAs, which play
      important regulatory functions by interacting with the 3' untranslated region
      (UTR) of target mRNAs. Through this mechanism, miR-223 was shown to regulate
      genes involved in mammalian haematopoiesis, both in physiological and
      pathological contexts. MiR-223 is essential for normal myelopoiesis in mammals,
      promoting granulocyte, osteoclast and megakaryocyte differentiation and
      suppressing erythropoiesis. However, there is a general lack of knowledge
      regarding miR-223 function in other vertebrates, which could help to clarify its
      role in other processes, such as development. In this work, we explored the
      functional conservation of miR-223 using zebrafish as a model. We show that miR
      223 gene structure and genomic context have been maintained between human and
      zebrafish. In addition, we identified 22 novel sequences of miR-223 precursor and
      demonstrate that it contains domains highly conserved among vertebrates,
      suggesting function preservation throughout evolution. Furthermore, collected
      evidences show that miR-223 expression is highly correlated with haematopoietic
      events and osteoclastogenesis throughout zebrafish development. In adults,
      expression of miR-223 in zebrafish tissues mimics the distribution in mice, with
      high levels found in the major fish haematopoietic organ, the head kidney. These
      results suggest a conservation of miR-223 role in haematopoiesis, and
      osteoclastogenesis between zebrafish and human. Accordingly, validated targets of
      miR-223 in mammalian models were investigated and defined as putative targets in
      zebrafish, by in silico and gene expression analysis. Our data compiles critical
      evidence showing that miR-223, a highly conserved miRNA, appears to have kept
      similar regulatory functions throughout evolution. 

PMID- 25869933
TI  - Transcriptome analysis of the plateau fish (Triplophysa dalaica): Implications
      for adaptation to hypoxia in fishes.
AB  - Triplophysa dalaica, endemic species of Qinghai-Tibetan Plateau, is informative
      for understanding the genetic basis of adaptation to hypoxic conditions of high
      altitude habitats. Here, a comprehensive gene repertoire for this plateau fish
      was generated using the Illumina deep paired-end high-throughput sequencing
      technology. De novo assembly yielded 145, 256 unigenes with an average length of
      1632 bp. Blast searches against GenBank non-redundant database annotated 74,594
      (51.4%) unigenes encoding for 30,047 gene descriptions in T. dalaica. Functional
      annotation and classification of assembled sequences were performed using Gene
      Ontology (GO), clusters of euKaryotic Orthologous Groups (KOG) and Kyoto
      Encyclopedia of Genes and Genomes (KEGG) analysis. After comparison with other
      fish transcriptomes, including silver carp (Hypophthalmichthys molitrix) and mud
      loach (Misgurnus anguillicaudatus), 2621 high-quality orthologous gene alignments
      were constructed among these species. 61 (2.3%) of the genes were identified as
      having undergone positive selection in the T. dalaica lineage. Within the
      positively selected genes, 13 genes were involved in hypoxia response, of which
      11 were listed in HypoxiaDB. Furthermore, duplicated hif-alpha (hif-1alphaA/B and
      hif-2alphaA/B), EGLN1 and PPARA candidate genes involved in adaptation to hypoxia
      were identified in T. dalaica transcriptome. Branch-site model in PAML validated
      that hif-1alphaB and hif-2alphaA genes have undergone positive selection in
      T.dalaica. Finally, 37,501 simple sequence repeats (SSRs) and 19,497 high-quality
      single nucleotide polymorphisms (SNPs) were identified in T. dalaica. The
      identified SSR and SNP markers will facilitate the genetic structure, population
      geography and ecological studies of Triplophysa fishes.

PMID- 25869931
TI  - A new quorum-sensing system (TprA/PhrA) for Streptococcus pneumoniae D39 that
      regulates a lantibiotic biosynthesis gene cluster.
AB  - The Phr peptides of the Bacillus species mediate quorum sensing, but their
      identification and function in other species of bacteria have not been
      determined. We have identified a Phr peptide quorum-sensing system (TprA/PhrA)
      that controls the expression of a lantibiotic gene cluster in the Gram-positive
      human pathogen, Streptococcus pneumoniae. Lantibiotics are highly modified
      peptides that are part of the bacteriocin family of antimicrobial peptides. We
      have characterized the basic mechanism for a Phr-peptide signaling system in S.
      pneumoniae and found that it induces the expression of the lantibiotic genes when
      pneumococcal cells are at high density in the presence of galactose, a main sugar
      of the human nasopharynx, a highly competitive microbial environment. Activity of
      the Phr peptide system is not seen when pneumococcal cells are grown with
      glucose, the preferred carbon source and the most prevalent sugar encountered by
      S. pneumoniae during invasive disease. Thus, the lantibiotic genes are expressed
      under the control of both cell density signals via the Phr peptide system and
      nutritional signals from the carbon source present, suggesting that quorum
      sensing and the lantibiotic machinery may help pneumococcal cells compete for
      space and resources during colonization of the nasopharynx. 

PMID- 25869934
TI  - Expression profiles of MiRNAs for intrinsic musculature of the forepaw and biceps
      in the rat model simulating irreversible muscular atrophy of obstetric brachial
      plexus palsy.
AB  - Clinically in obstetric brachial plexus palsy (OBPP), irreversible atrophy of
      intrinsic musculature of the hand in denervation occurs much earlier than that of
      denervated arm muscles. With the aim of finding clues to explain this, the miRNA
      expression profile of denervated intrinsic musculature of the forepaw (IMF) and
      that of the denervated biceps were examined by microarray screening in the rat
      model simulating irreversible muscular atrophy caused by pan-plexus lesions of
      OBPP, and potential targets of specifically dysregulated miRNAs were predicted
      with use of bioinformatics analysis. It was found that denervated IMF and biceps
      had their own specifically dysregulated miRNAs, respectively, as compared with
      control. Analysis of Gene Ontology and of pathway showed that those specifically
      dysregulated miRNAs and their target genes might participate in self-regulation
      of neuromuscular junctions (NMJs). These outcomes suggest that self-regulative
      mechanism of NMJs may be different between denervated IMF and denervated biceps
      in the rat model simulating irreversible muscular atrophy of OBPP. 

PMID- 25869935
TI  - UKIP wrong about HIV data and health tourism, say campaigners.

PMID- 25869936
TI  - Patient performance-based plan parameter optimization for prostate cancer in
      tomotherapy.
AB  - The purpose of this study is to evaluate the influence of treatment-planning
      parameters on the quality of treatment plans in tomotherapy and to find the
      optimized planning parameter combinations when treating patients with prostate
      cancer under different performances. A total of 3 patients with prostate cancer
      with Eastern Cooperative Oncology Group (ECOG) performance status of 2 or 3 were
      included in this study. For each patient, 27 treatment plans were created using a
      combination of planning parameters (field width of 1, 2.5, and 5cm; pitch of
      0.172, 0.287, and 0.43; and modulation factor of 1.8, 3, and 3.5). Then, plans
      were analyzed using several dosimetrical indices: the prescription isodose to
      target volume (PITV) ratio, homogeneity index (HI), conformity index (CI), target
      coverage index (TCI), modified dose HI (MHI), conformity number (CN), and quality
      factor (QF). Furthermore, dose-volume histogram of critical structures and
      critical organ scoring index (COSI) were used to analyze organs at risk (OAR)
      sparing. Interestingly, treatment plans with a field width of 1cm showed more
      favorable results than others in the planning target volume (PTV) and OAR
      indices. However, the treatment time of the 1-cm field width was 3 times longer
      than that of plans with a field width of 5cm. There was no substantial decrease
      in treatment time when the pitch was increased from 0.172 to 0.43, but the PTV
      indices were slightly compromised. As expected, field width had the most
      significant influence on all of the indices including PTV, OAR, and treatment
      time. For the patients with good performance who can tolerate a longer treatment
      time, we suggest a field width of 1cm, pitch of 0.172, and modulation factor of
      1.8; for the patients with poor performance status, field width of 5cm, pitch of
      0.287, and a modulation factor of 3.5 should be considered. 

PMID- 25869937
TI  - Say goodbye to tribes in the new house fly classification: A new molecular
      phylogenetic analysis and an updated biogeographical narrative for the Muscidae
      (Diptera).
AB  - House flies are one of the best known groups of flies and comprise about 5000
      species worldwide. Despite over a century of intensive taxonomic research on
      these flies, classification of the Muscidae is still poorly resolved. Here we
      brought together the most diverse molecular dataset ever examined for the
      Muscidae, with 142 species in 67 genera representing all tribes and all
      biogeographic regions. Four protein coding genes were analyzed: mitochondrial CO1
      and nuclear AATS, CAD (region 4) and EF1-alpha. Maximum likelihood and Bayesian
      approaches were used to analyze five different partitioning schemes for the
      alignment. We also used Bayes factors to test monophyly of the traditionally
      accepted tribes and subfamilies. Most subfamilial taxa were not recovered in our
      analyses, and accordingly monophyly was rejected by Bayes factor tests. Our
      analysis consistently found three main clades of Muscidae and so we propose a new
      classification with only three subfamilies without tribes. Additionally, we
      provide the first timeframe for the diversification of all major lineages of
      house flies and examine contemporary biogeographic hypotheses in light of this
      timeframe. We conclude that the muscid radiation began in the Paleocene to Eocene
      and is congruent with the final stages of the breakup of Gondwana, which resulted
      in the complete separation of Antarctica, Australia, and South America. With this
      newly proposed classification and better understanding of the timing of
      evolutionary events, we provide new perspectives for integrating morphological
      and ecological evolutionary understanding of house flies, their taxonomy,
      phylogeny, and biogeography. 

PMID- 25869938
TI  - Optimizing Central Nervous System Drug Development Using Molecular Imaging.
AB  - Advances in multimodality fusion imaging technologies promise to accelerate the
      understanding of the systems biology of disease and help in the development of
      new therapeutics. The use of molecular imaging biomarkers has been proven to
      shorten cycle times for central nervous system (CNS) drug development and thereby
      increase the efficiency and return on investment from research. Imaging
      biomarkers can be used to help select the molecules, doses, and patients most
      likely to test therapeutic hypotheses by stopping those that have little chance
      of success and accelerating those with potential to achieve beneficial clinical
      outcomes. CNS imaging biomarkers have the potential to drive new medical care
      practices for patients in the latent phases of progressive neurodegenerative
      disorders by enabling the detection, preventative treatment, and tracking of
      disease in a paradigm shift from today's approaches that have to see the overt
      symptoms of disease before treating it. 

PMID- 25869939
TI  - The Potential of the CNS as a Reservoir for HIV-1 Infection: Implications for HIV
      Eradication.
AB  - The ability of HIV-1 to establish latent infection is a key obstacle to its
      eradication despite the existence of effective antiretroviral drugs. The brain
      has been postulated as a reservoir for latent infection, but its role in HIV
      persistence remains unclear. In this review, we discuss the evidence surrounding
      the role of the central nervous system (CNS) as a viral reservoir and the
      potential challenges this might present in eradicating HIV. The strategies for
      eradication of HIV and their application to latent CNS infection are explored.
      Finally, we outline new developments in drug delivery and new therapeutic
      modalities designed to target HIV infection in the CNS. 

PMID- 25869940
TI  - Southern Africa: the Highest Priority Region for HIV Prevention and Care
      Interventions.
AB  - The global HIV pandemic began to expand rapidly in southern Africa a decade later
      than was noted in central Africa, Europe, the Caribbean, and North America.
      Multiple factors played a role in this rapid expansion which led Southern Africa
      to become the most heavily afflicted region for HIV/AIDS globally. In this issue
      of Current HIV/AIDS Reports, investigators with active research interests in the
      region have reviewed key elements of the causes of and responses to the epidemic.
      Putative causes of the high HIV prevalence in the region are discussed, including
      host and viral biology, human behavior, politics and policy, structural factors,
      health services, health workforce, migration, traditional healers' role, and
      other issues. Regional epidemiological trends are described and forecasted.
      Issues related to the continuum of HIV care and treatment are highlighted. We
      hope that the reviews will prove useful to those policymakers, health care
      workers, and scientists who are striving to reduce the burden of HIV in the
      southern African region, as well as prove insightful for key issues of broader
      global relevance. 

PMID- 25869941
TI  - Abdominal visceral fat accumulation measured by computed tomography associated
      with an increased risk of gallstone disease.
AB  - BACKGROUND AND AIM: Visceral adiposity is a strong determinant of insulin
      resistance, which decreases cholecystokinin response sensitivity, and increases
      cholesterol saturation in the gallbladder bile; thus, it potentially relates to
      gallstone disease development. We aimed to investigate whether visceral fat
      measured by computed tomography (CT) is a risk factor for gallstone disease.
      METHODS: A cohort of 717 participants undergoing CT and ultrasonography was
      analyzed. The associations between body mass index (BMI), visceral adipose tissue
      (VAT) area, subcutaneous adipose tissue (SAT) area, and gallstone disease were
      analyzed adjusted for age, sex, hypertension, diabetes, and dyslipidemia.
      RESULTS: In multivariate analysis, gallstone disease was significantly associated
      with VAT and SAT areas for both categorical data and trend (P for trend < 0.001,
      0.009), but not body mass index (BMI). Among patients with BMI < 25, gallstone
      disease remained significantly associated with VAT area (P for trend 0.021) and
      SAT area (P for trend 0.005). Interactions between the obesity indices and being
      elderly on the risk of gallstone disease were found; specifically BMI (P =
      0.005), SAT (P < 0.001), and VAT (P = 0.154). A significant association between
      all obesity indices and gallstone disease was seen in patients aged < 65 but not
      among those aged >= 65. However, no significant association was noted between the
      obesity indices and sex. CONCLUSIONS: CT-measured adipose tissue, rather than
      BMI, was a better predictor for risk of gallstone disease. This finding applies
      to younger people or even those with normal body weight, suggesting the
      importance of abdominal visceral fat accumulation in the development of gallstone
      disease.

PMID- 25869943
TI  - Are invasive autopsies necessary?

PMID- 25869942
TI  - Cost-effectiveness analysis of interventions for migraine in four low- and middle
      income countries.
AB  - BACKGROUND: Evidence of the cost and effects of interventions for reducing the
      global burden of migraine remains scarce. Our objective was to estimate the
      population-level cost-effectiveness of evidence-based migraine interventions and
      their contributions towards reducing current burden in low- and middle-income
      countries. METHODS: Using a standard WHO approach to cost-effectiveness analysis
      (CHOICE), we modelled core set intervention strategies for migraine, taking
      account of coverage and efficacy as well as non-adherence. The setting was
      primary health care including pharmacies. We modelled 26 intervention strategies
      implemented during 10 years. These included first-line acute and prophylactic
      drugs, and the expected consequences of adding consumer-education and provider
      training. Total population-level costs and effectiveness (healthy life years
      [HLY] gained) were combined to form average and incremental cost-effectiveness
      ratios. We executed runs of the model for the general populations of China,
      India, Russia and Zambia. RESULTS: Of the strategies considered, acute treatment
      of attacks with acetylsalicylic acid (ASA) was by far the most cost-effective and
      generated a HLY for less than US$ 100. Adding educational actions increased
      annual costs by 1-2 US cents per capita of the population. Cost-effectiveness
      ratios then became slightly less favourable but still less than US$ 100 per HLY
      gained for ASA. An incremental cost of > US$ 10,000 would have to be paid per
      extra HLY by adding a triptan in a stepped-care treatment paradigm. For
      prophylaxis, amitriptyline was more cost-effective than propranolol or
      topiramate. CONCLUSIONS: Self-management with simple analgesics was by far the
      most cost-effective strategy for migraine treatment in low- and middle-income
      countries and represents a highly efficient use of health resources. Consumer
      education and provider training are expected to accelerate progress towards
      desired levels of coverage and adherence, cost relatively little to implement,
      and can therefore be considered also economically attractive. Evidence-based
      interventions for migraine should have as much a claim on scarce health resources
      as those for other chronic, non-communicable conditions that impose a significant
      burden on societies.

PMID- 25869944
TI  - Weighing bitemark evidence : A postmodern perspective.
AB  - Forensic bitemark identification is a demanding area of odontological expertise
      that typically relies on a three-stage process consisting of a detailed
      examination of the bitemark, an examination and clinical evaluation of the
      suspect's dentition, occlusion, and temporomandibular joint, followed by the
      interpretation of the available evidence. Because the investigator faces a
      complex body of often incomplete or ambiguous data that has to be reconciled in
      order to arrive at a conclusion, uncertainty plays a large role in the process.
      This review evaluates modern bitemark analysis in the light of Daubert's
      criteria, with special reference to modern ideas about reasoning under
      uncertainty. It concludes that more than 150 years of developments in bitemark
      evidence still leaves us without some sort of consensual basis to decide whether
      or not bitemark evidence should be admitted. However, recent scientific attempts
      to introduce new bitemark techniques and also to evaluate the evidential
      reliability of bitemark evidence have offered exciting new perspectives on this
      debate. 

PMID- 25869945
TI  - Zolpidem : Forensic aspects for the toxicologist and pathologist.
AB  - Zolpidem (Ambien), a nonbenzodiazepine hypnotic, is indicated for the short-term
      treatment of insomnia. Because it has become the most widely prescribed sleep aid
      in the United States, it is being increasingly detected in a variety of forensic
      specimens, and its interaction with other medications is being questioned. We
      present a comprehensive overview of the basic chemistry, pharmacokinetics, and
      pharmacodynamics of zolpidem; its interaction with other prescription drugs; its
      effects on driving and motor skills; and its analysis and interpretation in
      forensic casework. 

PMID- 25869946
TI  - Congenital lesions associated with airway narrowing, respiratory distress, and
      unexpected infant and early childhood death.
AB  - A review was undertaken of the range of possible congenital lesions of the major
      airways and adjacent tissues that may cause critical compromise of luminal
      diameter with resultant respiratory arrest from airway occlusion. Lesions
      included micrognathic syndromes, macroglossia, choanal atresia and stenosis,
      tumors and choristomas, posterior lingual masses, laryngeal atresia and stenosis,
      laryngeal webs, laryngeal cysts and laryngoceles, laryngomalacia, tracheomalacia,
      and bronchomalacia. An autopsy approach to possible congenital obstructive
      lesions of the upper airway requires: (1) review of the clinical and family
      histories looking specifically at the nature of the terminal episode; (2)
      external examination looking for dysmorphic syndromes with mandibular or mid
      facial hypoplasia; and (3) internal examination with layer dissection of the soft
      tissues of the neck and en bloc removal of the upper aerodigestive tract, with
      photographic recording and histological sampling. 

PMID- 25869947
TI  - Dose-concentration relationships of methadone and EDDP in hair of patients on a
      methadone-maintenance program.
AB  - After controlled oral administration of D,L-methadone solution (15-260 mg/day) in
      the context of a methadone-maintenance program, concentrations of methadone and 2
      ethylidine-1,5-dimethyl-3,3-diphenyl-l-pyrrolidine (EDDP), in head hair were
      determined (N=41), using a fully automated headspace solid-phase microextraction
      procedure in combination with gas chromatography and mass spectrometry (HS
      SPME/GC/MS).Methadone was present in all samples in concentrations ranging from
      0.25 to 13.29 ng/mg (mean 2.69+/-0.45 ng/mg). EDDP was also present in every
      sample in concentrations ranging from 0.05 to 2.17 ng/mg (mean 0.43+/-0.08). The
      concentration ratio methadone/EDDP was 7.5+/-5.7 in the proximal segments, but
      decreased to 4.8+/-1.4 in the distal segments. A statistically significant
      correlation between the intake dose and the methadone and EDDP concentrations in
      the subjects' hair could be established only in the proximal segments (r=0.913
      for methadone and r=0.901 for EDDP), but not in the distal segments. In all, 131
      segments analyzed, the correlation coefficient was r=0.760 for methadone and
      r=0.738 for EDDP. In comparison to the dose-concentration relationship reported
      in the literature, we found a better correlation with higher correlation
      coefficients especially in the proximal segments.However, owing to a broad
      distribution in the correlation between dosage and concentration, the
      determination of methadone and EDDP in hair holds only limited information about
      prior methadone administration. 

PMID- 25869948
TI  - Postmortem grading of cerebral contusions : A proposed modification of the adams'
      contusion index with re-definition of anatomic markers.
AB  - In the 1970s, J. H. Adams and other researchers at the Institute of Neurological
      Sciences, Glasgow, Scotland introduced a grading system for the quantification
      and analysis of contusions of the brain. They derived a brain contusion index
      based on regional surface distribution and parenchymal depth of contusions of the
      brain. Following a subsequent modification of this scheme in the 1980s, they
      recommended evolving modifications that will fit a variety of possible
      applications. Having tested the applicability of this grading system for the
      forensic/medico-legal autopsy, we have encountered some applied anatomic
      limitations and have derived a modification that addresses these limitations in
      reference to the forensic/medico-legal autopsy.We recommend a two-tier system
      based on the Adams' system, which quantifies contusions of the brain by the gyral
      spread of contusions and by the parenchymal depth of penetration of contusions
      with a re-definition of the lobar distinctions and classifications of the brain.
      Gyral spread is assigned a grading scheme of 0-3 and the parenchymal depth of
      contusions is assigned a grading scheme of 0-4. A lobar contusion score is
      derived by multiplying the two assigned grades. A total brain contusion index is
      derived by summating all the lobar contusion scores. This reproducible grading
      system can be applied to routine bench forensic neuropathology reporting, court
      room illustrations and in comparative research analysis of brain trauma subjects.

PMID- 25869949
TI  - The estimation of the time since death using temperatures recorded from the
      external auditory canal : Part II: Using single temperatures from this site to
      estimate the time since death with consideration of environmental or body
      "factors" that could affect the estimation.
AB  - In this second of two articles, single external auditory canal (EAC) temperatures
      from cases of suspicious deaths were used to verify the hypothesis that a single
      EAC temperature can be used to estimate a time since death (TSD). Two different
      types of thermometers were used (infrared and alcohol-in-glass) to record ambient
      and body temperatures, which were in turn applied to previously published
      algorithms without the use of corrective factors to estimate the TSD. In
      addition, 18 anatomical, environmental, and daily activity "factors" were
      investigated as to whether they may influence the temperature within the EAC and
      thus require the introduction of a corrective factor into an algorithm, other
      than one used to take into account the difference between the rectal and EAC
      temperature during life and after death. Of the ones examined, only head
      position, wind speed, daily circadian rhythm, drinking of hot drinks, and
      possibly mental thought were shown to influence temperature, but the difference
      was so small that the introduction of a corrective factor into an algorithm was
      considered unnecessary. Finally, this article provides a summary of both
      articles, with general recommendations to those who have to use a temperature
      recorded from the EAC in estimating a TSD. 

PMID- 25869950
TI  - Forensic pathology and forensic epidemiology of suicides in allegheny county,
      pennsylvania : A 10-year retrospective review (1990-1999).
AB  - Suicide has assumed epidemic proportions and constitutes a major public health
      issue throughout the United States. Suicide remains one of the top eight leading
      causes of death, accounting for approximately 30,000 deaths annually. The
      understanding and prevention of suicide requires a multidisciplinary approach
      that involves psychosocial and medical specialties starting with a forensic
      analysis of the characteristics of suicide. The aim of this 10-year (1990-1999)
      retrospective study was threefold: first, to examine the forensic epidemiological
      characteristics of suicides examined by the Allegheny County Coroner's Office;
      second, to describe emerging epidemiological patterns of suicide; and finally, to
      make recommendations for preventive measures. A total of 1447 suicides were
      identified, with 1164 males (80%) and 283 females (20%) resulting in a male to
      female ratio of 4:1. The race distribution comprised 90% whites, 9% blacks, and
      1% other races. The age of suicide victims ranged from 13 to 96 years old with a
      peak within the 31- to 40-year-old age group, which represented 24.5% of all
      suicides. Overall, 40% of the victims were single and more blacks than whites
      were single. The greatest number of suicides occurred in July, with the least in
      December. Suicides most frequently occurred between 9:01 AM and 3:00 PM. Suicide
      notes were present in 29% of all suicides. Firearm injuries, hanging, and drug
      overdose were the leading methods of suicide. Use of firearms was the leading
      method of suicide among both sexes. Female drug overdose deaths outnumbered male
      drug overdose deaths. The 10 most common overdose drugs were all central nervous
      system depressants, with amitriptyline being the most common prescription
      overdose drug. Based on reported antecedent trends in suicides, we make two
      recommendations regarding suicide prevention: (1) physicians should be educated
      to replace the prescription of older and more toxic antidepressants such as
      amitriptyline with newer and less toxic antidepressants such as serotonin
      reuptake inhibitors; and (2) firearms should be made inaccessible to individuals
      with risk factors for suicide, especially in the home. 

PMID- 25869951
TI  - Morphometrical, histopathological, immunohistochemical, and ultrastructural
      findings in human pulmonary tissue destruction following penetrating low-velocity
      firearm injuries to the lungs.
AB  - This autopsy-based study investigated the morphological correlates of pulmonary
      tissue destruction following fatal penetrating gunshot wounds to the lungs using
      morphometry, histology, immunohistochemistry, and scanning electron microscopy on
      whole human lungs fixed-expanded via formalin inflation. As the residue of
      temporary cavity formation, mantle-like hemorrhagic destruction zones were seen
      surrounding the missile track that showed an eccentric, conical extension
      enlarging toward subpleural lung segments. In addition, circumscribed, satellite
      like bleeding zones at distances of up to 5.5 cm beyond the border of the
      permanent cavity were observed that corresponded to interstitial perivascular
      hemorrhages around larger and smaller pulmonary vessels on the micro
      morphological level. These multifocal hemorrhages within macroscopically
      unaffected parts of pulmonary tissue at some distance from the actual missile
      track may represent unrecognized, life-threatening intrapulmonary bleeding
      sources in survivors, potentially leading to ventilation-perfusion mismatch and
      progressive lung failure. A further noticeable microscopic and ultrastructural
      finding was that of club-shaped distensions of ruptured alveolar septa strictly
      limited to the extent of the temporary cavity. These club-shaped distensions of
      ruptured alveolar septa seem to represent a special feature of alveolar
      architectural damage that can be explained by the dynamics of the temporary
      cavity formation: the radial acceleration and overdistension of tissue during
      temporary cavitation initiates stretch mechanisms of the displaced tissue,
      causing the alveolar septa to rupture with subsequent foreshortening and pursing
      of elastic alveolar fibers. 

PMID- 25869952
TI  - Vomiting, diarrhea, and sudden death with recent southeast asian travel : Fatal
      colchicine toxicity.
AB  - A 41-year-old male was referred for autopsy from a hospital with a diagnosis of
      sepsis of uncertain etiology. As he had recently been attached to a military base
      in Southeast Asia, and had only just returned home, there was considerable
      concern that an unknown infectious agent may have been involved, which would
      necessitate screening of coworkers and contacts, with possible quarantine of the
      facilities where he had been working. His clinical history included a day of
      vomiting and diarrhea. Despite rehydration and antibiotic therapy, he died within
      hours of hospitalization. His only past medical history was of gout, for which he
      was prescribed allopurinol. At autopsy there was evidence of multiorgan failure
      but no focal sepsis. Postmortem microbiological tests including blood cultures,
      lung swab, colonic fecal culture, and a small intestinal swab were negative.
      Histological examination of small intestinal mucosa demonstrated numerous mitotic
      figures, which, in concert with the presentation, raised the possibility of
      colchicine toxicity. Subsequent reinterview of family members confirmed that the
      deceased had ingested an unknown quantity of colchicine on the day prior to his
      illness and toxicological evaluation demonstrated a toxic/potentially lethal
      level of 0.05 mg/L of colchicine in the blood. Death was therefore attributed to
      colchicine toxicity and not to occult sepsis. This case clearly demonstrates that
      causes of gastrointestinal illness other than sepsis need to be considered when
      patients have presented with vomiting and diarrhea. There may also be
      considerable public health implications if a death is incorrectly attributed to
      sepsis and then a specific infectious agent is not identified. Maintaining a
      broad approach to diagnostic possibilities is essential if forensic practitioners
      are to maintain a useful role in the investigation of unexpected deaths. 

PMID- 25869953
TI  - Contact-free isolation of sperm and epithelial cells by laser microdissection and
      pressure catapulting.
AB  - With the PALM MicroBeam system, precise laser microdissection of single cells
      from cell smears or tissue preparations is possible. Furthermore, this system
      uses a contact-free and therefore contamination-free laser pressure catapulting
      technique in which high energy generated by a focused laser pulse catapults
      single dissected cells into a collecting vessel. In this study, this technique
      was tested for forensic purposes with smear preparations from postcoital vaginal
      swabs, sperm swabs, and buccal cell swabs on different types of microscopic
      slides. Apart from super-frosted slides, cutting and catapulting of selected
      cells was possible in all cases. Subsequent polymerase chain reaction was
      performed using the genRES MPX-2 Amplification Kit. In the case of sperm cells
      stained with hematoxylin and eosin, fragments larger than approximately 200 bp
      could not be detected. Partial genetic profiles were obtained for DNA amounts
      originating from only two cell equivalents. Complete profiles, however, were
      observed with all preparations of a minimum of 10 epithelial cells, demonstrating
      a potential benefit of this technique for the contamination-free forensic
      analysis of extremely small specimens or mixed stains. 

PMID- 25869955
TI  - Erratum.

PMID- 25869954
TI  - Nonhuman DNA.
AB  - DNA has now been used to aid criminal investigation for more than 20 years. The
      vast majority of this evidence has been produced by profiling of human genetic
      material. However, DNA profiling technology is not restricted to the human
      genome. Regions of genetic material displaying similar characteristics to markers
      used for forensic purposes in the human genome have been identified in many other
      animal species. Although nonhuman DNA profiling has been used for a small number
      of forensic investigations, the full potential of this evidence type has yet to
      be realized. 

PMID- 25869956
TI  - Psoralen derivatives as inhibitors of NF-kappaB interaction: the critical role of
      the furan ring.
AB  - Simplified analogues of previously reported NF-kappaB interaction inhibitors,
      lacking the furan moiety, were synthesized and evaluated by performing
      experiments based on electrophoretic mobility shift assay (EMSA). The synthetic
      modifications led to simpler coumarin derivatives with lower activity allowing to
      better understand the minimal structural requirement for the binding to NF
      kappaB.

PMID- 25869957
TI  - Acanthamoeba misidentification and multiple labels: redefining genotypes T16,
      T19, and T20 and proposal for Acanthamoeba micheli sp. nov. (genotype T19).
AB  - Acanthamoeba species are ubiquitous amoebae able to cause important infections in
      humans and other vertebrates. The full/near-full sequences (>2000 bp) of the
      small subunit ribosomal RNA gene (SSU rDNA or 18S rDNA) are used to cluster
      Acanthamoeba as genotypes, labeled T1 to T20. Genotype T15 remains an exception,
      being described only partially on a 1500-bp fragment. Strains are thus usually
      identified based on their 18S identity matches with reference strains, often
      using shorter (<500 bp) diagnostic fragments of the gene. Nevertheless, short
      fragments (<1000 bp) have been used to propose genotypes. This has been
      criticized, and doubts arise therefore on possible confusion leading to classify
      distinct partial sequences with a same label(s). We demonstrate herein that
      several partial sequences misassigned either to T16 or to T4, actually belong to
      at least two separate and distinct genotypes. We obtained the full 18S rDNA of a
      strain previously typed as T16 on the basis of a small fragment and demonstrated
      that it actually belongs to the recently described T19. We propose the name
      Acanthamoeba micheli sp. nov., for this strain. Furthermore, partial molecular
      phylogenies were performed to show that several other misassigned T16 partial
      sequences belong to a new genotype. This latter includes also misassigned T4
      partial sequences, only recently available as full sequences and labeled as T20.
      We thus reassign these partial sequences to the genotype T20. Longer sequences,
      ideally at least 90 % of the total gene length, should be obtained from strains
      to ensure reliable diagnostic and phylogenetic results. 

PMID- 25869958
TI  - Synergy between rhinacanthins from Rhinacanthus nasutus in inhibition against
      mosquito cytochrome P450 enzymes.
AB  - The cytochrome P450 monooxygenases play a major role in insecticide
      detoxification and become a target for development of insecticide synergists. In
      this study, a collection of rhinacanthins (rhinacanthin-D, -E, -G, -N, -Q, and 
      H/I) purified from Rhinacanthus nasutus, in addition to previously purified
      rhinacanthin-B and -C, were isolated. These compounds displayed various degrees
      of inhibition against benzyloxyresorufin-O-debenzylation mediated by CYP6AA3 and
      CYP6P7 which were implicated in pyrethroid resistance in Anopheles minimus
      malaria vector. Inhibition modes and kinetics were determined for each of
      rhinacanthins. Cell-based inhibition assays by rhinacanthins employing 3-(4, 5
      dimethylthiazol-2-y-l)-2, 5-diphenyltetrazolium bromide (MTT) cytotoxicity test
      were explored their synergistic effects with cypermethrin toxicity on CYP6AA3-
      and CYP6P7-expressing Spodoptera frugiperda (Sf9) cells. Rhinacanthin-B, -D, -E, 
      G, and -N exhibited mechanism-based inhibition against CYP6AA3, an indication of
      irreversible inhibition, while rhinacanthin-B, -D, -G, and -N were mechanism
      based inhibitors of CYP6P7. There was structure-function relationship of these
      rhinacanthins in inhibition effects against both enzymes. In vitro enzymatic
      inhibition assays revealed that there were synergistic interactions among
      rhinacanthins, except rhinacanthin-B and -Q, in inhibition against both enzymes.
      These rhinacanthins exerted synergism with cypermethrin toxicity on Sf9 cells
      expressing each of the two P450 enzymes via P450 inhibition and in addition could
      interact in synergy to further increase cypermethrin toxicity. The inhibition
      potentials, synergy among rhinacanthins in inhibition against the P450
      detoxification enzymes, and synergism with cypermethrin toxicity of the R.
      nasutus constituents of reported herein could be beneficial to implement
      effective resistance management of mosquito vector control. 

PMID- 25869959
TI  - Tick species (Acari: Ixodida) in Antalya City, Turkey: species diversity and
      seasonal activity.
AB  - Ticks (Acari: Ixodida) are an important group of ectoparasites of vertebrates.
      Most species are known vectors of diseases including Lyme disease, Q fever, and
      Crimean-Congo hemorrhagic fever. A 3-year research was conducted in Antalya,
      Turkey, to determine tick species composition, seasonal abundance, and spatial
      distribution. The study was carried out in five districts (Aksu, Dosemealti,
      Kepez, Konyaalti, and Muratpasa) of Antalya Metropolitan Municipality area in
      Turkey, between May 2010 and May 2013, where 1393 tick specimens were collected
      from domestic and wild animals (cattle, goats, sheep, hedgehogs, tortoises, dogs,
      cats, chickens) and from the environment. The collected ticks were preserved in
      70 % alcohol and then were identified. Five genus and eight hard and soft tick
      species were identified, including Argas persicus, Rhipicephalus annulatus, R.
      sanguineus, R. turanicus, Hyalomma aegyptium, H. marginatum, Haemaphysalis parva,
      and Dermacentor niveus. Rhipicephalus sanguineus, R. turanicus, and H. aegyptium
      were the most common tick species in Antalya city. Rhipicephalus turanicus and R.
      sanguineus were the most abundant tick species infesting dogs in the city. The
      hosts of H. aegyptium are primarily tortoises in Antalya. The results of this
      research will contribute to establishing appropriate measures to control tick
      infestations on animals and humans and their environment in the city of Antalya. 

PMID- 25869960
TI  - Ultrastructural characteristics of the caeca of basal polyopisthocotylean
      monogeneans of the families Chimaericolidae and Hexabothriidae parasitic on
      cartilaginous fishes.
AB  - Ultrastructural differences are shown between the caecal organization in three
      blood-feeding polyopisthocotylean monogeneans, i.e., the chimaericolid
      Chimaericola leptogaster from the holocephalan Chimaera monstrosa and two
      hexabothriids, Callorhynchocotyle callorhynchi from the holocephalan
      Callorhynchus capensis and Rajonchocotyle emarginata from the elasmobranch
      Amblyraja radiata. In C. leptogaster, digestive cells and connecting syncytium,
      joined close to the luminal surface by septate junctions, are arranged
      alternately along the caecal epithelial wall; the nuclear regions of both cell
      types are sunk below the general level of the caecal epithelium; a concave
      depression on the apical margin of the digestive cells bears lamellae; and this
      depression is covered by a lamellate bubble formed by thin projections emanating
      from the connecting syncytium. The luminal surface of the connecting syncytium is
      covered with outgrowths terminating in the form of long, narrow processes. In R.
      emarginata and C. callorhynchi, the predominant digestive cells are at different
      stages of development and occur in groups, developing digestive cells bulge into
      the caecal lumen from the connecting syncytium with contact sites present close
      to the luminal surface, and the luminal surface structures of both the connecting
      syncytium and the digestive cells are short lamellae. In these two hexabothriids,
      a holocrine (or apocrine) process for the elimination of digestive product is
      assumed via the detachment of fully differentiated, bulging digestive cells.
      Free, apparently sloughed digestive cells and residual bodies are present within
      the caecal lumen, and replacement digestive cells are numerous in the connecting
      syncytium. In the chimaericolid, free bubbles containing residual bodies and
      portions of digestive cells filled with degenerating digestive vesicles occur in
      the caecal lumen along with large amounts of male and female reproductive
      material. The usefulness of characteristics of the caecal ultrastructure as
      taxonomic traits at the family level is discussed. 

PMID- 25869961
TI  - Expellency, anti-feeding and speed of kill of a dinotefuran-permethrin
      pyriproxyfen spot-on (Vectra(r)3D) in dogs weekly challenged with adult fleas
      (Ctenocephalides felis) for 1 month-comparison to a spinosad tablet
      (Comfortis(r)).
AB  - This study was designed to compare the efficacy of two ectoparasiticides against
      adult fleas on dogs: a topical (DPP, dinotefuran-permethrin-pyriproxyfen) and a
      systemic (S, spinosad). Dogs (n = 48; 10.21-22.86 kg BW) were allocated to six
      groups of eight dogs each (C1, C4, DPP1, DPP4, S1, S4). Dogs in the treated
      groups were administered a topical (3.6 mL of DPP) or a tablet (665 or 1040 mg of
      S) on day 0. Infestations with 100 unfed fleas (Ctenocephalides felis) occurred
      on days -6, -1, 2, 7, 14, 21 and 28. An additional untreated group (QC, n = 6)
      was involved to evaluate the flea-anti-feeding efficacy. These dogs were infested
      once with 150 fleas prior to combing of at least 50 live fleas from each dog 5 or
      10 min after infestation. In the treated group, dislodged dead and moribund fleas
      were collected from dogs 5, 10, 15 and 60 min (DPP1, S1) or 5, 10, 30 and 240 min
      (DPP4, S4) post-treatment and subsequent flea infestations on pans placed
      underneath the cages. Fleas were counted and removed from dogs by combing 1 (C1,
      DPP1, S1) or 4 h (C4, DPP4, S4) post-treatment and subsequent infestations.
      Quantitative PCR analysis of the canine cytochrome b gene was conducted on
      dislodged fleas collected from treated and control (QC) dogs 5 and 10 min after
      post-treatment infestations. The number of gene copies was used as a marker of
      blood volume ingested by fleas. Dislodgeability and insecticidal efficacy were
      calculated using arithmetic means. A rapid onset of killing was observed for DPP
      with 12.7 % of dead and moribund fleas being dislodged in average from dogs as
      soon as 5 min after infestation. DPP exhibited a significantly higher and
      sustained speed of kill than S. The average insecticidal efficacy was 86 +/- 8.8
      and 95.3 +/- 2.1 % with DPP, whereas it was only 33.7 +/- 19.9 and 57.6 +/- 18.6
      % with S at respectively 1 and 4 h after weekly reinfestations. The DPP
      combination significantly inhibited the feeding of fleas (89 % reduction) up to
      onset of flea mortality for 1-month post-treatment. 

PMID- 25869962
TI  - [Long-term effects of radiation on the spine - Results of a cohort of symptomatic
      survivors of childhood and review of the literature].
AB  - OBJECTIVES: The objective of the present retrospective study was to describe the
      clinical, radiological and bone characteristics of long-term survivors who have
      received radiotherapy involving some part of the vertebral column for certain
      childhood tumors. PATIENTS AND METHODS: Monocentric descriptive study of a cohort
      of patients followed at Gustave-Roussy in the framework of long-term monitoring
      treated for a solid tumor in childhood with radiotherapy on part of the spine and
      having back pain and/or spinal deformity have been addressed in the Service of
      Musculoskeletal Rehabilitation at the Cochin Hospital. For each patient, were
      performed standardized radiographs of the entire spine and spinal MRI. RESULTS:
      Eighteen patients were evaluated (average age of 35.4 +/- 6.9 years; mean age at
      radiation therapy: 3.6 +/- 2.8 years). Original tumors were nephroblastoma (9
      cases), neuroblastoma (4 cases) and medulloblastoma (3 cases). Of the 15 patients
      analyzed by X-rays of the entire spine, 67% (10/15) patients had scoliosis (2
      with a Cobb angle > 20 degrees ), 73% (11/15) had an abnormal thoracic kyphosis,
      67% (10/15) had abnormal lumbar lordosis. Of the 16 patients analyzed by MRI, 75%
      (12/16) had discopathies or anomalies of the discal plate, 63% (10/16) had mild
      abnormalities of bone marrow. Muscle abnormalities were common (81%, 13/16).
      CONCLUSION: The main risk factors of spinal deformities are intraductal tumor,
      spinal surgery, spinal radiotherapy and a young age at the time of the cancer.
      These cured children require dedicated monitoring. Currently, this risk is
      reduced with the actual techniques of radiotherapy.

PMID- 25869963
TI  - Reply to the comments to our paper "Contaminant levels in Norwegian farmed
      Atlantic salmon (Salmo salar) in the 13-year period from 1999 to 2011".

PMID- 25869964
TI  - A comparative study of folate receptor-targeted doxorubicin delivery systems:
      dosing regimens and therapeutic index.
AB  - Ligand-receptor mediated targeting may affect differently the performance of
      supramolecular drug carriers depending on the nature of the nanocarrier. In this
      study, we compare the selectivity, safety and activity of doxorubicin (Dox)
      entrapped in liposomes versus Dox conjugated to polymeric nanocarriers in the
      presence or absence of a folic acid (FA)-targeting ligand to cancer cells that
      overexpress the folate receptor (FR). Two pullulan (Pull)-based conjugates of Dox
      were synthesized, (FA-PEG)-Pull-(Cyst-Dox) and (NH2-PEG)-Pull-(Cyst-Dox). The
      other delivery systems are Dox loaded PEGylated liposomes (PLD, Doxil(r)) and the
      FR-targeted version (PLD-FA) obtained by ligand post-insertion into the
      commercial formulation. Both receptor-targeted drug delivery systems (DDS) were
      shown to interact in vitro specifically with cells via the folate ligand.
      Treatment of FR-overexpressing human cervical carcinoma KB tumor-bearing mice
      with three-weekly injections resulted in slightly enhanced anticancer activity of
      PLD-FA compared to PLD and no activity for both pullulan-based conjugates. When
      the DDS were administered intravenously every other day, the folated-Pull
      conjugate and the non-folated-Pull conjugate displayed similar and low antitumor
      activity as free Dox. At this dosing regimen, the liposome-based formulations
      displayed enhanced antitumor activity with an advantage to the non-folated
      liposome. However, both liposomal formulations suffered from toxicity that was
      reversible following treatment discontinuation. Using a daily dosing schedule,
      with higher cumulative dose, the folated-Pull conjugate strongly inhibited tumor
      growth while free Dox was toxic at this regimen. For polymeric constructs,
      increasing dose intensity and cumulative dose strongly affects the therapeutic
      index and reveals a major therapeutic advantage for the FR-targeted formulation.
      All DDS were able to abrogate doxorubicin-induced cardiotoxicity. This study
      constitutes the first side-by-side comparison of two receptor-targeted ligand
      bearing systems, polymer therapeutics versus nanoparticulate systems, evaluated
      in the same mouse tumor model at several dosing regimens.

PMID- 25869966
TI  - Evaluating the Effects of Function-Based Interventions With Deaf or Hard-of
      Hearing Students.
AB  - This study examined the effectiveness of function-based interventions with
      students who are deaf or hard of hearing (D/HH). The participants were 3
      elementary-aged males attending a center school for the deaf who exhibited
      chronic off-task behaviors throughout the school day. This study was conducted
      across 2 phases: (a) a descriptive functional behavior assessment (FBA) was
      conducted for each participant and (b) individualized function-based
      interventions were developed based on the results of the FBAs, followed by the
      implementation of the interventions in each classroom using a single-subject,
      ABAB reversal design. The function-based interventions significantly improved
      each participant's on-task behavior in his classroom environment. Furthermore,
      social validity ratings by each teacher revealed that the interventions were
      effective, easy to implement, and appropriate for each participant. Implications
      for application of the procedures used in this study with the D/HH population,
      limitations, and directions for future research are discussed. 

PMID- 25869967
TI  - A design path for the hierarchical self-assembly of patchy colloidal particles.
AB  - Patchy colloidal particles are promising candidates for building blocks in
      directed self-assembly. To be successful the surface patterns need to be simple
      enough to be synthesized, while feature-rich enough to cause the colloidal
      particles to self-assemble into desired structures. Achieving this is a challenge
      for traditional synthesis methods. Recently it has been suggested that surface
      patterns themselves can be made to self-assemble. In this paper we present a
      design path for the hierarchical targeted self-assembly of patchy colloidal
      particles based on self-assembling surface patterns. At the level of the surface
      structure, we use a predictive method utilizing the universality of stripes and
      spots, coupled with stoichiometric constraints, to cause highly specific and
      functional patterns to self-assemble on spherical surfaces. We use a minimalistic
      model of an alkanethiol on gold as a demonstration, showing that even with
      limited control over the interaction between surface constituents we can obtain
      patterns that cause the colloidal particles themselves to self-assemble into
      various complex geometric structures, such as strings, membranes, cubic
      aggregates and colloidosomes, as well as various crystalline patterns. 

PMID- 25869965
TI  - Cationic liposome-hyaluronic acid hybrid nanoparticles for intranasal vaccination
      with subunit antigens.
AB  - Here we report the development of a new cationic liposome-hyaluronic acid (HA)
      hybrid nanoparticle (NP) system and present our characterization of these NPs as
      an intranasal vaccine platform using a model antigen and F1-V, a candidate
      recombinant antigen for Yersinia pestis, the causative agent of plague.
      Incubation of cationic liposomes composed of DOTAP and DOPE with anionic HA
      biopolymer led to efficient ionic complexation and formation of homogenous
      liposome-polymer hybrid NPs, as evidenced by fluorescence resonance energy
      transfer, dynamic light scattering, and nanoparticle tracking analyses.
      Incorporation of cationic liposomes with thiolated HA allowed for facile surface
      decoration of NPs with thiol-PEG, resulting in the formation of DOTAP/HA core-PEG
      shell nanostructures. These NPs, termed DOTAP-HA NPs, exhibited improved
      colloidal stability and prolonged antigen release. In addition, cytotoxicity
      associated with DOTAP liposomes (LC50~0.2mg/ml) was significantly reduced by at
      least 20-fold with DOTAP-HA NPs (LC50>4mg/ml), as measured with bone marrow
      derived dendritic cells (BMDCs). Furthermore, NPs co-loaded with ovalbumin (OVA)
      and a molecular adjuvant, monophosphoryl lipid A (MPLA) promoted BMDC maturation
      and upregulation of co-stimulatory markers, including CD40, CD86, and MHC-II, and
      C57BL/6 mice vaccinated with NPs via intranasal route generated robust OVA
      specific CD8(+) T cell and antibody responses. Importantly, intranasal
      vaccination with NPs co-loaded with F1-V and MPLA induced potent humoral immune
      responses with 11-, 23-, and 15-fold increases in F1-V-specific total IgG, IgG1,
      and IgG2c titers in immune sera by day 77, respectively, and induced balanced
      Th1/Th2 humoral immune responses, whereas mice immunized with the equivalent
      doses of soluble F1-V vaccine failed to achieve sero-conversion. Overall, these
      results suggest that liposome-polymer hybrid NPs may serve as a promising vaccine
      delivery platform for intranasal vaccination against Y. pestis and other
      infectious pathogens.

PMID- 25869968
TI  - Mitochondrial DNA haplogroup phylogeny of the dog: Proposal for a cladistic
      nomenclature.
AB  - Canis lupus familiaris mitochondrial DNA analysis has increased in recent years,
      not only for the purpose of deciphering dog domestication but also for forensic
      genetic studies or breed characterization. The resultant accumulation of data has
      increased the need for a normalized and phylogenetic-based nomenclature like
      those provided for human maternal lineages. Although a standardized
      classification has been proposed, haplotype names within clades have been
      assigned gradually without considering the evolutionary history of dog mtDNA.
      Moreover, this classification is based only on the D-loop region, proven to be
      insufficient for phylogenetic purposes due to its high number of recurrent
      mutations and the lack of relevant information present in the coding region. In
      this study, we design 1) a refined mtDNA cladistic nomenclature from a
      phylogenetic tree based on complete sequences, classifying dog maternal lineages
      into haplogroups defined by specific diagnostic mutations, and 2) a coding region
      SNP analysis that allows a more accurate classification into haplogroups when
      combined with D-loop sequencing, thus improving the phylogenetic information
      obtained in dog mitochondrial DNA studies. 

PMID- 25869970
TI  - Homeopathy, hormesis, nanoparticles and nanostructures.

PMID- 25869971
TI  - Hormesis: principles and applications.
AB  - Hormesis has emerged as a central concept in biological and biomedical sciences
      with significant implications for clinical medicine and environmental risk
      assessment. This paper assesses the historical foundations of the dose-response
      including the threshold, linear and hormetic models, the occurrence and frequency
      of the hormetic dose response in the pharmacological and toxicological
      literature, its quantitative and temporal features, and underlying mechanistic
      bases. Based upon this integrative foundation the application of hormesis to the
      process of risk assessment for non-carcinogens and carcinogens is explored. 

PMID- 25869972
TI  - Historical foundations of hormesis.
AB  - The present paper provides an historical assessment of the concept of hormesis
      and its relationship to homeopathy and modern medicine. It is argued that the
      dose-response concept was profoundly influenced by the conflict between
      homeopathy and traditional medicine and that decisions on which dose-response
      model to adopt were not based on "science" but rater on historical antipathies.
      While the historical dispute between homeopathy and traditional medicine has long
      since subsided, their impact upon the field has been enduring and generally
      unappreciated, profoundly adversely affecting current drug development,
      therapeutic strategies and environmental risk assessment strategies and policies.

PMID- 25869973
TI  - Hormesis within a mechanistic context.
AB  - This paper provides an assessment of the mechanistic foundations of hormesis and
      how such understandings evolved over the course of the past century. Particular
      emphasis is placed on recent developments particularly with respect to receptor
      based and cell signaling-based pathways. Of particular importance is that the
      quantitative feature of the hormetic dose response are independent of mechanism. 

PMID- 25869974
TI  - Unequal brothers : are homeopathy and hormesis linked?
AB  - The debate between those who believe homeopathy and hormesis derive from the same
      root and those who believe the two are different phenomena is as old as hormesis.
      It is an emotionally loaded discussion, with both sides fielding arguments which
      are far from scientific. Careful analysis of the basic paradigms of the two
      systems questions the claim of the homeopaths, who find similarities between
      them. The authors discuss these paradigms, indicating the differences between the
      claims of homeopathy and hormesis. It is time for thorough and serious research
      to lay this question to rest. One possible approach is to compare the activity of
      a hormetic agent, prepared in the usual way, with that of the same agent in the
      same concentration prepared homeopathically by serial dilution and succussion. 

PMID- 25869975
TI  - Gas nanobubbles and aqueous nanostructures: the crucial role of dynamization.
AB  - Nanobubbles (NBs) have been a subject of intensive research over the past decade.
      Their peculiar characteristics, including extremely low buoyancy, longevity,
      enhanced solubility of oxygen in water, zeta potentials and burst during
      collapse, have led to many applications in the industrial, biological and medical
      fields. NBs may form spontaneously from dissolved gas but the process is greatly
      enhanced by gas supersaturation and mechanical actions such as dynamization.
      Therefore, the formation of NBs during the preparation of homeopathic dilutions
      under atmospheric pressure cannot be ignored. I suggested in 2009 the involvement
      of NBs in nanometric superstructures revealed in high dilutions using NMR
      relaxation. These superstructures seemed to increase in size with dilution, well
      into the ultramolecular range (>12c). I report here new experiments that confirm
      the involvement of NBs and prove the crucial role of dynamization to create
      superstructures specific to the solute. A second dynamization was shown to
      enhance or regenerate these superstructures. I postulate that superstructures
      result from a nucleation process of NBs around the solute, with shells of highly
      organized water (with ions and silicates if any) which protect the solute against
      out-diffusion and behave as nucleation centres for further dilution steps. The
      sampling tip may play an active role by catching the superstructures and thus
      carry the encaged solute across the dilution range, possibly up to the
      ultramolecular range. The superstructures were not observed at low dilution,
      probably because of a destructuring of the solvent by the solute and/or of an
      inadequate gas/solute ratio. 

PMID- 25869976
TI  - Hormetic effects of extremely diluted solutions on gene expression.
AB  - This paper summarizes the results of investigations showing how molecular
      biological tools, such as DNA-microarrays, can provide useful suggestions about
      the behaviour of human organisms treated with microamounts of drugs or
      homeopathic medicines. The results reviewed here suggest firstly that the action
      of drugs is not quenched by ultra-high dilution and proceeds through modulation
      of gene expressions. The efficacy of drug solutions seems to be maintained in
      ultra-highly diluted preparations, a fact which constitutes a challenge to the
      dogma of quantization of matter. The second and more important result is that the
      different gene expression profiles of cell systems treated with the same drugs at
      different dilutions suggest the existence of hormetic mechanisms. The gene
      expression profiles of cells treated with copper(II) sulfate, Gelsemium
      sempervirens and Apis mellifica, are characterized by the same common denominator
      of the concentration-dependent inversion of gene expression, which can justify at
      a molecular level the concept of simile adopted in homeopathy. The main
      conclusion we draw from these results is that these procedures provide new kinds
      of information and a tool for disclosing the mechanisms involved in hormetic
      effects. The application of these effects to modern medicine may allow
      researchers to conceive unprecedented therapeutic applications or to optimize the
      currently used ones in the framework of a low-dose pharmacology based on a
      reliable experimental platform. 

PMID- 25869977
TI  - Enhancement of adaptive biological effects by nanotechnology preparation methods
      in homeopathic medicines.
AB  - Multiple studies have demonstrated that traditional homeopathic manufacturing
      reagents and processes can generate remedy source and silica nanoparticles (NPs).
      Homeopathically-made NPs would initiate adaptive changes in an organism as a
      complex adaptive system (CAS) or network. Adaptive changes would emerge from
      several different endogenous amplification processes that respond to exogenous
      danger or threat signals that manufactured nanomaterials convey, including (1)
      stochastic resonance (SR) in sensory neural systems and (2) time-dependent
      sensitization (TDS)/oscillation. SR is nonlinear coherent amplification of a weak
      signal by the superposition of a larger magnitude white noise containing within
      it the same frequencies of the weak signal. TDS is progressive response magnitude
      amplification and oscillatory reversal in response direction to a given low dose
      at physiological limits with the passage of time. Hormesis is an overarching
      adaptive phenomenon that reflects the observed nonlinear adaptive dose-response
      relationship. Remedies would act as enhanced micro- and nanoscale forms of their
      source material via direct local ligand-receptor interactions at very low
      potencies and/or by triggering systemic adaptive network dynamical effects via
      their NP-based electromagnetic, optical, and quantum mechanical properties at
      higher potencies. Manufacturing parameters including dilution modify sizes,
      shapes, and surface charges of nanoparticles, thereby causing differences in
      physico-chemical properties and biological effects. Based on surface area, size,
      shape, and charge, nanoparticles adsorb a complex pattern of serum proteins,
      forming a protein corona on contact that constitutes a unique biological
      identity. The protein corona may capture individualized dysfunctional biological
      mediator information of the organism onto the surfaces of the salient, i.e.,
      resonant, remedy nanostructures. SR would amplify this weak signal from the
      salient remedy NPs with protein corona adsorbed, leading to sensitized nonlinear
      dynamical modulation of gene expression and associated changes in biological
      signaling pathways. When the system reaches its physiological limits during a
      homeopathic aggravation or the natural disease state, the amplified remedy signal
      triggers a nonlinear reversal in dynamical direction back towards health. 

PMID- 25869978
TI  - Cell sensitivity, non-linearity and inverse effects.
AB  - It has been claimed that the homeopathic principle of 'similarity' (or 'similia')
      and the use of individualized remedies in extremely low doses conflicts with
      scientific laws, but this opinion can be disputed on the basis of recent
      scientific advances. Several mechanisms to explain the responsiveness of cells to
      ultra-low doses and the similarity as inversion of drug effects, have again been
      suggested in the framework of hormesis and modern paradoxical pharmacology. Low
      doses or high dilutions of a drug interact only with the enhanced sensitivities
      of regulatory systems, functioning as minute harmful stimuli to trigger specific
      compensatory healing reactions. Here we review hypotheses about homeopathic drug
      action at cellular and molecular levels, and present a new conceptual model of
      the principle of similarity based on allosteric drug action. While many common
      drugs act through orthostatic chemical interactions aimed at blocking undesired
      activities of enzymes or receptors, allosteric interactions are associated with
      dynamic conformational changes and functional transitions in target proteins,
      which enhance or inhibit specific cellular actions in normal or disease states.
      The concept of allostery and the way it controls physiological activities can be
      broadened to include diluted/dynamized compounds, and may constitute a working
      hypothesis for the study of molecular mechanisms underlying the inversion of drug
      effects. 

PMID- 25869979
TI  - Keyhole System: A Computer-Assisted Designed and Computer-Assisted Manufactured
      Maxillomandibular Complex Repositioner in Orthognathic Surgery.
AB  - Currently, virtual orthognathic surgery using the CAD/CAM program and three
      dimensional printing technology has provided a valuable tool supporting accurate
      surgical planning and precise surgery. However, despite the advancements in
      CAD/CAM virtual surgical planning, accurately reproducing surgical planning from
      a virtual surgery to the operating field is still challenging. Here, we report
      the Keyhole system as a method that has constantly provided us with consistent
      results during double-jaw surgery, especially during this age of ever increasing
      aesthetic demand from patients. 

PMID- 25869980
TI  - What Is the Quality of the Evidence in the Craniomaxillofacial Surgery
      Literature?
AB  - PURPOSE: Evidence-based practice is an important concept for surgeons. The
      purpose of this study was to assess the quality of evidence in the
      craniomaxillofacial surgery (CMS) literature. MATERIALS AND METHODS: This was a
      retrospective cohort study of patient-oriented articles published in 9 journals.
      The primary predictor variable was the year of publication (September 2007 to
      August 2008 or September 2012 to August 2013). Secondary predictor variables were
      journal, impact factor, subject (eg, reconstruction, esthetic surgery), and
      funding. The outcome variable was the level of evidence (levels 1 to 4),
      evaluated using the Center for Evidence-Based Medicine criteria. Descriptive,
      bivariate, and regression statistics were computed. RESULTS: The study sample
      included 2,824 articles. The mean weighted journal impact factor was 1.6 +/- 0.6
      (range, 0.7 to 2.9). Fifty-two percent of articles were published in the Journal
      of Craniofacial Surgery or the Journal of Oral and Maxillofacial Surgery. The
      most frequent subject area was craniomaxillofacial pathology (934 articles;
      33.1%). Eight percent of studies were funded. There were 97 (3.4%) level 1, 562
      (19.9%) level 2, 228 (8.1%) level 3, and 1,937 (68.6%) level 4 studies. In a
      multiple regression model, year of publication (odds ratio [OR] = 1.2; P = .05),
      impact factor (OR = 2.4; P < .001), category (OR = 1.4; P < .001), and funding
      (OR = 1.6; P < .001) were associated with higher-quality evidence. CONCLUSION:
      The quality of evidence in the CMS literature is low. Higher levels of evidence
      are associated with more recent publications, journal impact factor, topic area,
      and funding.

PMID- 25869981
TI  - Applications of Computer-Assisted Navigation for the Minimally Invasive Reduction
      of Isolated Zygomatic Arch Fractures.
AB  - PURPOSE: Computer-assisted navigation has been widely used in oral and
      maxillofacial surgery. The purpose of this study was to describe the applications
      of computer-assisted navigation for the minimally invasive reduction of isolated
      zygomatic arch fractures. PATIENTS AND METHODS: All patients identified as having
      isolated zygomatic arch fractures presenting to the authors' department from
      April 2013 through November 2014 were included in this prospective study.
      Minimally invasive reductions of isolated zygomatic arch fractures were performed
      on these patients under the guidance of computer-assisted navigation. The
      reduction status was evaluated by postoperative computed tomography (CT) 1 week
      after the operation. Postoperative complications and facial contours were
      evaluated during follow-up. Functional recovery was evaluated by the difference
      between the preoperative maximum interincisal mouth opening and that at the final
      follow-up. RESULTS: Twenty-three patients were included in this case series. The
      operation proceeded well in all patients. Postoperatively, all patients displayed
      uneventful healing without postoperative complication. Postoperative CT showed
      exact reduction in all cases. Satisfactory facial contour and functional recovery
      were observed in all patients. The preoperative maximal mouth opening ranged from
      8 to 25 mm, and the maximal mouth opening at the final follow-up ranged from 36
      to 42 mm. CONCLUSIONS: Computer-assisted navigation can be used not only for
      guiding zygomatic arch fracture reduction, but also for assessing reduction.
      Computer-assisted navigation is an effective and minimally invasive technique
      that can be applied in the reduction of isolated zygomatic arch fractures.

PMID- 25869982
TI  - Prognostic Factors of Survival From Intractable Oronasal Bleeding After
      Successful Transarterial Embolization.
AB  - PURPOSE: To evaluate the prognostic factors that influence the survival of
      patients with traumatic intractable oronasal bleeding treated by transarterial
      embolization (TAE). MATERIALS AND METHODS: Patients who received TAE for
      intractable oronasal bleeding in the National Taiwan University Hospital from
      2002 through 2013 were included in the study. Retrospective reviews were
      undertaken to collect relevant clinical and neuroradiologic data that might be
      correlated with patients' survival. The Wilcoxon rank-sum test or Fisher exact
      test was adopted to analyze differences between the survival group and the
      mortality group. Odds ratios were estimated by univariate logistic regression.
      RESULTS: TAE successfully controlled the bleeding in 24 of 26 patients (92.3%)
      who had severe craniofacial injury in the 12-year period. Of the 24 patients with
      successful TAE, 13 patients were discharged alive from the hospital. The overall
      survival rate was 50% (13 of 26). Significantly higher initial Glasgow Coma Scale
      (GCS) score (P = .01) and lower Injury Severity Score (ISS; P < .01) were present
      in the survival group than in the mortality group by the Wilcoxon rank-sum test.
      Moreover, patients with an ISS of at least 30, a GCS score lower than 9, initial
      hemoglobin level lower than 10 g/dL, and computed tomographic (CT) findings of a
      brain midline shift had statistically higher odds ratios predicting mortality
      than their counterparts as estimated by univariate logistic regression.
      CONCLUSIONS: The results of this study showed that the combination of diagnostic
      angiography and therapeutic embolization is effective treatment for intractable
      oronasal bleeding in patients with severe craniofacial injury. The prognosis in
      patients who were rescued with successful TAE was statistically correlated with
      the severity of trauma and concomitant brain injury. An ISS of at least 30, a GCS
      score lower than 9, an initial hemoglobin level lower than 10, and CT findings of
      a brain midline shift were strong predictors for mortality.

PMID- 25869983
TI  - Angled Osteotomy Design Aimed to Influence the Lingual Fracture Line in Bilateral
      Sagittal Split Osteotomy: A Human Cadaveric Study.
AB  - PURPOSE: The traditional osteotomy design in the bilateral sagittal split
      osteotomy includes a horizontal lingual bone cut, a connecting sagittal bone cut,
      and a vertical buccal bone cut perpendicular to the inferior mandibular cortex.
      The buccal bone cut extends as an inferior border cut into the lingual cortex.
      This study investigated a modified osteotomy design including an angled oblique
      buccal bone cut that extended as a posteriorly aimed inferior border cut near the
      masseteric tuberosity. MATERIALS AND METHODS: The authors implemented a
      randomized controlled study. The study sample was comprised of 28 cadaveric
      dentulous mandibles. The primary outcome variable was the pattern of lingual
      fracture induced using the conventional (n = 14) and modified (n = 14) osteotomy
      designs. The secondary outcome variables included the incidence of bad splits and
      the status of the inferior alveolar nerve (IAN). Descriptive and bivariate
      statistics were computed. RESULTS: The angled osteotomy design resulted in a
      significantly larger number of the lingual fractures originating from the
      inferior border cut (odds ratio [OR] = 1.54; 95% confidence interval [CI], 1.27
      1.86; P < .01), with a significantly more posterior relation of the fracture line
      to the mandibular canal (OR = 2.11; 95% CI, 1.22-3.63; P < .01) and foramen (OR =
      1.99; 95% CI, 1.28-3.08; P < .01). No bad splits occurred with the angled design,
      whereas 3 bad splits occurred with the conventional design, although this
      difference was not statistically significant (OR = 1.11; 95% CI, 0.99-1.25; P =
      .07). IAN status was comparable between designs, although the nerve more
      frequently required manipulation from the proximal mandibular segment when the
      conventional design was used (OR = 1.21; 95% CI, 0.99-1.47; P = .06). CONCLUSION:
      The results suggest that the angled osteotomy design promotes a more posterior
      lingual fracture originating from the inferior border cut and a trend was
      apparent that this also might decrease the incidence of bad splits and IAN
      entrapment. These results must be carefully extrapolated to the clinical setting,
      with future studies clarifying these findings.

PMID- 25869984
TI  - Comparison of Neck Screw and Conventional Fixation Techniques in Mandibular
      Condyle Fractures Using 3-Dimensional Finite Element Analysis.
AB  - PURPOSE: To compare the mechanical stress on the mandibular condyle after the
      reduction and fixation of mandibular condylar fractures using the neck screw and
      2 other conventional techniques according to 3-dimensional finite element
      analysis. MATERIALS AND METHODS: A 3-dimensional finite element model of a
      mandible was created and graphically simulated on a computer screen. The model
      was fixed with 3 different techniques: a 2.0-mm plate with 4 screws, 2 plates (1
      1.5-mm plate and 1 2.0-mm plate) with 4 screws, and a neck screw. Loads were
      applied that simulated muscular action, with restrictions of the upper movements
      of the mandible, differentiation of the cortical and medullary bone, and the
      virtual "folds" of the plates and screws so that they could adjust to the
      condylar surface. Afterward, the data were exported for graphic visualization of
      the results and quantitative analysis was performed. RESULTS: The 2-plate
      technique exhibited better stability in regard to displacement of fractures,
      deformity of the synthesis materials, and minimum and maximum tension values. The
      results with the neck screw were satisfactory and were similar to those found
      when a miniplate was used. CONCLUSION: Although the study shows that 2 isolated
      plates yielded better results compared with the other groups using other fixation
      systems and methods, the neck screw could be an option for condylar fracture
      reduction.

PMID- 25869985
TI  - Interdisciplinary Surgical Management of Multiple Facial Fractures With Image
      Guided Navigation.
AB  - PURPOSE: To evaluate the effectiveness of interdisciplinary surgical management
      of multiple facial fractures with image-guided surgical navigation. PATIENTS AND
      METHODS: From 2011 through 2014, 36 patients with multiple facial fractures were
      enrolled in the study. With individual virtual 3-dimensional (3D) modeling,
      interdisciplinary planning and surgical simulation were carried out on an Accu
      Navi software platform. Through an interactive collaboration among specialists,
      all patients underwent 1-stage open reduction under guidance of the navigation
      system. The outcome was assessed by superimposing the postoperative 3D computed
      tomographic (CT) model on the preoperative plan and clinical examination.
      RESULTS: Through the registration procedure, an accurate match between the actual
      intraoperative position and the CT images was achieved within a systematic error
      of 1 mm. The fractured bone segments were released and repositioned according to
      the preoperative plan and simulation with the aid of instrument- and probe-based
      navigation. All patients underwent uneventful healing without serious
      complications. Postoperative assessment of surgical intervention showed a
      quantitative discrepancy less than 2 mm (1.49 +/- 0.27), showing a satisfactory
      concordance. CONCLUSION: In the interdisciplinary surgical management of multiple
      facial fractures, image-guided surgical navigation, including preoperative
      planning, surgical simulation, postoperative assessment, and computer-assisted
      navigation, proved an optimal strategy and valuable option for this potentially
      complicated procedure.

PMID- 25869986
TI  - Mirror-Imaged Rapid Prototype Skull Model and Pre-Molded Synthetic Scaffold to
      Achieve Optimal Orbital Cavity Reconstruction.
AB  - PURPOSE: Reconstruction of traumatic orbital wall defects has evolved to restore
      the original complex anatomy with the rapidly growing use of computer-aided
      design and prototyping. This study evaluated a mirror-imaged rapid prototype
      skull model and a pre-molded synthetic scaffold for traumatic orbital wall
      reconstruction. PATIENTS AND METHODS: A single-center retrospective review was
      performed of patients who underwent orbital wall reconstruction after trauma from
      2012 to 2014. Patients were included by admission through the emergency
      department after facial trauma or by a tertiary referral for post-traumatic
      orbital deformity. Three-dimensional (3D) computed tomogram-based mirror-imaged
      reconstruction images of the orbit and an individually manufactured rapid
      prototype skull model by a 3D printing technique were obtained for each case.
      Synthetic scaffolds were anatomically pre-molded using the skull model as guide
      and inserted at the individual orbital defect. Postoperative complications were
      assessed and 3D volumetric measurements of the orbital cavity were performed.
      Paired samples t test was used for statistical analysis. RESULTS: One hundred
      four patients with immediate orbital defect reconstructions and 23 post-traumatic
      orbital deformity reconstructions were included in this study. All
      reconstructions were successful without immediate postoperative complications,
      although there were 10 cases with mild enophthalmos and 2 cases with persistent
      diplopia. Reoperations were performed for 2 cases of persistent diplopia and
      secondary touchup procedures were performed to contour soft tissue in 4 cases.
      Postoperative volumetric measurement of the orbital cavity showed nonsignificant
      volume differences between the damaged orbit and the reconstructed orbit (21.35
      +/- 1.93 vs 20.93 +/- 2.07 cm(2); P = .98). This protocol was extended to severe
      cases in which more than 40% of the orbital frame was lost and combined with
      extensive soft tissue defects. CONCLUSION: Traumatic orbital reconstruction can
      be optimized and successful using an individually manufactured rapid prototype
      skull model and a pre-molded synthetic scaffold by computer-aid design and
      manufacturing.

PMID- 25869987
TI  - Influence of Tacrolimus (FK506) on Nerve Regeneration Using Allografts: A Rat
      Sciatic Nerve Model.
AB  - PURPOSE: FK506 is an immunosuppressant agent used to prevent rejection after
      organ transplantation. The aim of the present study was to assess effects of
      tacrolimus (FK506) on peripheral nerve regeneration using allografts in a rat
      sciatic nerve model. MATERIALS AND METHODS: Thirty male white Wistar rats were
      divided randomly into a normal control (NC) group (n = 10), an allograft (ALLO)
      group (n = 10), and an FK506-treated (ALLO/FK506) group (n = 10). In the NC
      group, the left sciatic nerve was exposed through a gluteal muscle incision and,
      after homeostasis, the muscle was sutured. In the ALLO group, the left sciatic
      nerve was exposed through a gluteal muscle incision and transected proximal to
      the tibioperoneal bifurcation, where a 10-mm segment was excised. The same
      procedure was performed in the ALLO/FK506 group. The harvested nerves of the ALLO
      group served as allografts for the ALLO/FK506 group and vice versa. The NC and
      ALLO groups received sterile olive oil 300 MUL intraperitoneally once a day for 1
      week and the ALLO/FK506 group received FK506 300 MUL (1 mg/kg) intraperitoneally
      once a day for 1 week. RESULTS: Behavioral, functional, and biomechanical
      recovery and gastrocnemius muscle mass showed earlier regeneration of axons in
      the ALLO/FK506 than in the ALLO group (P < .05). Histomorphometric and
      immunohistochemical studies also showed earlier regeneration of axons in the
      ALLO/FK506 than in the ALLO group (P < .05). CONCLUSIONS: Administration of FK506
      could accelerate functional recovery of the sciatic nerve after nerve
      allografting. It could have clinical implications for the surgical management of
      patients after facial nerve transection.

PMID- 25869988
TI  - Parotid Sialocele or Traumatic Pseudocyst.

PMID- 25869989
TI  - Living with oropharyngeal dysphagia: effects of bolus modification on health
      related quality of life--a systematic review.
AB  - PURPOSE: Difficulty swallowing, oropharyngeal dysphagia, is widespread among many
      patient populations (such as stroke and cancer groups) and aged community
      dwelling individuals. It is commonly managed with bolus modification: altering
      food (usually cutting, mashing or pureeing) or fluids (typically thickening) to
      make them easier or safer to swallow. Although this treatment is ubiquitous,
      anecdotal evidence suggests patients dislike this management, and this may affect
      compliance and well-being. This review aimed to examine the impact of bolus
      modification on health-related quality of life. METHODS: A systematic review of
      the literature was conducted by speech pathologists with experience in
      oropharyngeal dysphagia. The literature search was completed with electronic
      databases, PubMed and Embase, and all available exclusion dates up to September
      2012 were used. The search was limited to English-language publications which
      were full text and appeared in peer-reviewed journals. RESULTS: Eight studies met
      the inclusion criteria. Generally, bolus modification was typically associated
      with worse quality of life. Modifications to foods appeared to be more
      detrimental than modifications to fluids, but this may be due to the increased
      severity of dysfunction that is implied by the necessity for significant
      alterations to foods. The number of studies retrieved was quite small. The
      diverse nature of methodologies, terminologies and assessment procedures found in
      the studies makes the results difficult to generalise. CONCLUSION: Overall, even
      though the severity of dysphagia may have been a confounding factor, the impact
      of bolus modification on health-related quality of life in patients with
      oropharyngeal dysphagia appears to be negative, with increased modification of
      food and fluids often correlating to a decreased quality of life. Further,
      associated disease factors, such as decreased life expectancy, may also have
      affected health-related quality of life. More research is needed.

PMID- 25869990
TI  - On-chip metal/polypyrrole quasi-reference electrodes for robust ISFET operation.
AB  - To operate an ion-sensitive field-effect transistor (ISFETs) it is necessary to
      set the electrolyte potential using a reference electrode. Conventional reference
      electrodes are bulky, fragile, and too big for applications where the electrolyte
      volume is small. Several researchers have proposed tackling this issue using a
      solid-state planar micro-reference electrode or a reference field-effect
      transistor. However, these approaches are limited by poor robustness, high cost,
      or complex integration with other microfabrication processes. Here we report a
      simple method to create robust on-chip quasi-reference electrodes by
      electrodepositing polypyrrole on micro-patterned metal leads. The electrodes were
      fabricated through the polymerization of pyrrole on patterned metals with a
      cyclic voltammetry process. Open circuit potential measurements were performed to
      characterize the polypyrrole electrode performance, demonstrating good stability
      (+/-1 mV), low drift (~1 mV h(-1)), and reduced pH response (5 mV per pH). In
      addition, the polypyrrole deposition was repeated in microelectrodes made of
      different metals to test compatibility with standard complementary metal-oxide
      semiconductor (CMOS) processes. Our results suggest that nickel, a metal commonly
      used in semiconductor foundries for silicide formation, is a good candidate to
      form the polypyrrole quasi-reference electrodes. Finally, the polypyrrole
      microelectrodes were used to operate foundry fabricated ISFETs. These experiments
      demonstrated that transistors biased with polypyrrole electrodes have pH
      sensitivity and resolution comparable to ones that are biased with standard
      reference electrodes. Therefore, the simple fabrication, high compatibility, and
      robust electrical performance make polypyrrole an ideal choice for the
      fabrication of outstanding microreference electrodes that enable robust and
      sensitive operation of multiple ISFET sensors on a chip. 

PMID- 25869991
TI  - "Until Mary Ellen held my hand..." The critical importance of touch in medicine.

PMID- 25869992
TI  - Prevalence and factors associated with polypharmacy in long-term care facilities:
      a systematic review.
AB  - OBJECTIVE: The objective of the study was to investigate the prevalence of, and
      factors associated with, polypharmacy in long-term care facilities (LTCFs).
      METHODS: MEDLINE, EMBASE, International Pharmaceutical Abstracts, Cumulative
      Index to Nursing and Allied Health Literature, and the Cochrane Library were
      searched from January 2000 to September 2014. Primary research studies in English
      were eligible for inclusion if they fulfilled the following criteria: (1)
      polypharmacy was quantitatively defined, (2) the prevalence of polypharmacy was
      reported or could be extracted from tables or figures, and (3) the study was
      conducted in a LTCF. Methodological quality was assessed using an adapted version
      of the Joanna Briggs Institute Critical Appraisal Checklist. RESULTS: Forty-four
      studies met the inclusion criteria and were included. Polypharmacy was most often
      defined as 5 or more (n = 11 studies), 9 (n = 13), or 10 (n = 11) medications.
      Prevalence varied widely between studies, with up to 91%, 74%, and 65% of
      residents taking more than 5, 9, and 10 medications, respectively. Seven studies
      performed multivariate analyses for factors associated with polypharmacy.
      Positive associations were found for recent hospital discharge (n = 2 studies),
      number of prescribers (n = 2), and comorbidity including circulatory diseases (n
      = 3), endocrine and metabolic disorders (n = 3), and neurological motor
      dysfunctioning (n = 3). Older age (n = 5), cognitive impairment (n = 3),
      disability in activities of daily living (n = 3), and length of stay in the LTCF
      (n = 3) were inversely associated with polypharmacy. CONCLUSIONS: The prevalence
      of polypharmacy in LTCFs is high, varying widely between facilities, geographical
      locations and the definitions used. Greater use of multivariate analysis to
      investigate factors associated with polypharmacy across a range of settings is
      required. Longitudinal research is needed to explore how polypharmacy has evolved
      over time.

PMID- 25869994
TI  - Policy Recommendation: The National Center for Prevention of Resident-to-Resident
      Aggression in Dementia.

PMID- 25869995
TI  - Collaborating With Businesses to Support and Sustain Research.
AB  - Financial assistance is necessary for sustaining research at universities.
      Business collaborations are a potential means for obtaining these funds. To
      secure funding, understanding the process for obtaining these business funds is
      important for nursing faculty members. Although faculty rarely request funding
      from businesses, they are often in a position to solicit financial support due to
      existing relationships with clinical agency administrators, staff, and community
      leaders. The economic support received from businesses provides outcomes in
      nursing research, research education, academic-service partnerships, and client
      health care. This article describes the steps and processes involved in
      successfully obtaining research funding from businesses. In addition, case
      examples for securing and maintaining funding from health care agencies (evidence
      based practice services) and from a health manufacturing company (product
      evaluation) are used to demonstrate the process. 

PMID- 25869993
TI  - Associations Between Ankle-Brachial Index and Cognitive Function: Results From
      the Lifestyle Interventions and Independence for Elders Trial.
AB  - OBJECTIVE: The objective of this study was to evaluate cross-sectional and
      longitudinal associations between ankle-brachial index (ABI) and indicators of
      cognitive function. DESIGN: Randomized clinical trial (Lifestyle Interventions
      and Independence for Elders Trial). SETTING: Eight US academic centers.
      PARTICIPANTS: A total of 1601 adults ages 70-89 years, sedentary, without
      dementia, and with functional limitations. MEASUREMENTS: Baseline ABI and
      interviewer- and computer-administered cognitive function assessments were
      obtained. These assessments were used to compare a physical activity intervention
      with a health education control. Cognitive function was reassessed 24 months
      later (interviewer-administered) and 18 or 30 months later (computer
      administered) and central adjudication was used to classify individuals as having
      mild cognitive impairment, probable dementia, or neither. RESULTS: Lower ABI had
      a modest independent association with poorer cognitive functioning at baseline
      (partial r = 0.09; P < .001). Although lower baseline ABI was not associated with
      overall changes in cognitive function test scores, it was associated with higher
      odds for 2-year progression to a composite of either mild cognitive impairment or
      probable dementia (odds ratio 2.60 per unit lower ABI; 95% confidence interval
      1.06-6.37). Across 2 years, changes in ABI were not associated with changes in
      cognitive function. CONCLUSION: In an older cohort sedentary individuals with
      dementia and with functional limitations, lower baseline ABI was independently
      correlated with cognitive function and associated with greater 2-year risk for
      progression to mild cognitive impairment or probable dementia.

PMID- 25869996
TI  - A duplex qPCR for the simultaneous detection of Escherichia coli O157:H7 and
      Listeria monocytogenes using LNA probes.
AB  - In this study, a duplex qPCR assay was developed for the needs of the Irish fish
      industry to screen for the two major food-borne pathogens of fish, Listeria
      monocytogenes and Escherichia coli O157:H7. The assay can claim positive or
      negative results for two pathogens in one go in only 20 h including 16 h
      universal pre-enrichment and compared to traditional ISO approved plate culture
      methods the labour and the cost involved in testing of one sample is reduced to
      minimum. The highly specific genomic areas targeted for PCR amplification in the
      assay are the hly gene for listeriolysin O (LLO) of L. monocytogenes and the stx
      gene for Shiga-like toxin expressed by E. coli O157:H7. The detection limit of
      the assay is consistent with the consumer protection limits of 1 pg genomic DNA
      or 1 CFU 25 g(-1) fish meat (with enrichment) allowing the test to be considered
      as a substitute to standard plate culture methods. SIGNIFICANCE AND IMPACT OF THE
      STUDY: The study highlights a novel duplex qPCR for Listeria monocytogenes and
      Escherichia coli O157:H7 that could be used as an alternative to plate-based ISO
      or singleplex PCR methods while minimizing the costs. The assay uses rapid DNA
      extraction methods and locked nucleic acid probes. Sensitivity and specificity
      are 100 and 98.95% respectively. The potential for quantitative rage of the assay
      is 10(8) -10(1) CFU ml(-1) .

PMID- 25869997
TI  - Cholesterol, statins, and dementia: what the cardiologist should know.
AB  - Alzheimer dementia (AD) is an important clinical problem that appears to be
      closely tied to comorbid cardiovascular disease, making it a relevant topic for
      the clinical cardiologist. Determinants of cardiovascular health, especially
      midlife dyslipidemia, are associated with an increased risk of dementia based on
      molecular and epidemiologic data. Given the potential role of dyslipidemia in the
      development of dementia, statins have been investigated as potential therapeutic
      options to slow or prevent disease. This review discusses the role of
      dyslipidemia and other cardiovascular risk factors in the pathogenesis of AD,
      with a focus on the existing evidence for the use of statin medications in the
      treatment and prevention of AD from observational studies and randomized clinical
      trials. Clinical questions for the practicing cardiologist are addressed. 

PMID- 25869998
TI  - Defining the genetic connection linking amyotrophic lateral sclerosis (ALS) with
      frontotemporal dementia (FTD).
AB  - Several genetic causes have been recently described for neurological diseases,
      increasing our knowledge of the common pathological mechanisms involved in these
      disorders. Mutation analysis has shown common causative factors for two major
      neurodegenerative disorders, ALS and FTD. Shared pathological and genetic markers
      as well as common neurological signs between these diseases have given rise to
      the notion of an ALS/FTD spectrum. This overlap among genetic factors causing
      ALS/FTD and the coincidence of mutated alleles (including causative, risk and
      modifier variants) have given rise to the notion of an oligogenic model of
      disease. In this review we summarize major advances in the elucidation of novel
      genetic factors in these diseases which have led to a better understanding of the
      common pathogenic factors leading to neurodegeneration. 

PMID- 25870000
TI  - Three-Dimensional Imaging of CD63 Recruitment at the Virological Synapse: HIV-1.

PMID- 25870001
TI  - [Patients with implanted ventricular assist devices : Challenge for emergency
      medicine].
AB  - Due to a huge increase in the implantation of ventricular assist devices (VAD)
      over the last few years and the enormous technical advances in functional safety,
      a growing number of patients with VAD are discharged from hospital, who are still
      considered to be severely ill. This results in an increased probability of these
      patients interacting with emergency services where personnel are unaware of the
      presence of a VAD, creating anxiety and uncertainty regarding how to treat these
      patients. This article presents an overview of the most common problems and
      pitfalls regarding VADs. It also presents an algorithm for dealing with
      emergencies involving these patients including the diagnostics, treatment and
      primary transport. 

PMID- 25869999
TI  - The Landscape of long noncoding RNA classification.
AB  - Advances in the depth and quality of transcriptome sequencing have revealed many
      new classes of long noncoding RNAs (lncRNAs). lncRNA classification has
      mushroomed to accommodate these new findings, even though the real dimensions and
      complexity of the noncoding transcriptome remain unknown. Although evidence of
      functionality of specific lncRNAs continues to accumulate, conflicting,
      confusing, and overlapping terminology has fostered ambiguity and lack of clarity
      in the field in general. The lack of fundamental conceptual unambiguous
      classification framework results in a number of challenges in the annotation and
      interpretation of noncoding transcriptome data. It also might undermine
      integration of the new genomic methods and datasets in an effort to unravel the
      function of lncRNA. Here, we review existing lncRNA classifications,
      nomenclature, and terminology. Then, we describe the conceptual guidelines that
      have emerged for their classification and functional annotation based on
      expanding and more comprehensive use of large systems biology-based datasets. 

PMID- 25870002
TI  - [Metformin-induced lactic acidosis : Severe symptoms with difficult diagnostics].
AB  - Metformin-induced lactic acidosis is a rare but severe disease for the individual
      patients. A case of a 64-year-old patient with diabetes mellitus type 2 suffering
      from this disease is presented where metformin accumulation was caused by
      prerenal acute kidney failure. The clinical evaluation up to the final diagnosis,
      the pathophysiology and the appropriate therapy are presented in detail.
      Additionally, the current guidelines regarding the perioperative management of
      metformin administration are summarized. The case described aims to direct
      attention to the rare but, nevertheless, severe symptoms of metformin-induced
      lactic acidosis. 

PMID- 25870003
TI  - An ultrasound-assisted system for the optimization of biodiesel production from
      chicken fat oil using a genetic algorithm and response surface methodology.
AB  - Biodiesel is a green (clean), renewable energy source and is an alternative for
      diesel fuel. Biodiesel can be produced from vegetable oil, animal fat and waste
      cooking oil or fat. Fats and oils react with alcohol to produce methyl ester,
      which is generally known as biodiesel. Because vegetable oil and animal fat
      wastes are cheaper, the tendency to produce biodiesel from these materials is
      increasing. In this research, the effect of some parameters such as the alcohol
      to-oil molar ratio (4:1, 6:1, 8:1), the catalyst concentration (0.75%, 1% and
      1.25% w/w) and the time for the transesterification reaction using
      ultrasonication on the rate of the fatty acids-to-methyl ester (biodiesel)
      conversion percentage have been studied (3, 6 and 9 min). In biodiesel production
      from chicken fat, when increasing the catalyst concentration up to 1%, the oil-to
      biodiesel conversion percentage was first increased and then decreased. Upon
      increasing the molar ratio from 4:1 to 6:1 and then to 8:1, the oil-to-biodiesel
      conversion percentage increased by 21.9% and then 22.8%, respectively. The
      optimal point is determined by response surface methodology (RSM) and genetic
      algorithms (GAs). The biodiesel production from chicken fat by ultrasonic waves
      with a 1% w/w catalyst percentage, 7:1 alcohol-to-oil molar ratio and 9 min
      reaction time was equal to 94.8%. For biodiesel that was produced by ultrasonic
      waves under a similar conversion percentage condition compared to the
      conventional method, the reaction time was decreased by approximately 87.5%. The
      time reduction for the ultrasonic method compared to the conventional method
      makes the ultrasonic method superior.

PMID- 25870004
TI  - A systematic review of barriers and facilitators to and interventions for proxy
      decision-making by family carers of people with dementia.
AB  - BACKGROUND: Relatives of people with dementia report that proxy decision-making
      is difficult and distressing. We systematically reviewed the literature about
      barriers and facilitators to family carers of people with dementia making proxy
      decisions, and interventions used to facilitate their decision-making. METHODS:
      We searched electronic databases and references of included papers up to February
      2014. Two authors independently evaluated study quality using a checklist.
      RESULTS: We included the 30/104 papers from our search which fitted predetermined
      criteria and prioritized higher quality papers. Family carers report that proxy
      decision-making is challenging and can be distressing, especially when decisions
      are made against the wishes of the care recipient and support from healthcare
      professionals is lacking. Decision-specific manualized aids have been developed,
      and while results for those supporting decisions about respite and percutaneous
      endoscopic gastrostomy (PEG) feeding have shown promising results in pilot
      trials, no intervention has yet been shown to significantly reduce decisional
      conflict or carer burden, or increase knowledge in randomized controlled trials;
      a decision aid for advance care planning increased decisional conflict.
      CONCLUSIONS: We recommend development and testing of decision aids targeting the
      decisions carers report finding most distressing, including those around where
      people should live, accessing services, and end of life treatments. Being
      provided with information to make decisions which have not previously been
      considered may increase feelings of conflict, suggesting these aids should be
      carefully targeted.

PMID- 25870005
TI  - Hypertension: New non-RAS peptide modulates the vasoregulatory effects of
      angiotensin II.

PMID- 25870006
TI  - Glomerular disease: Exacerbation of IgAN by gluten.

PMID- 25870009
TI  - Modulation of antioxidant systems by subchronic exposure to the aqueous extract
      of leaves from Achillea millefolium L. in rats.
AB  - We determined the effects of subchronic exposure to aqueous extract of leaves
      from Achillea millefolium (AE) on enzyme- and non-enzyme-dependent antioxidant
      systems in rats. Seven days treatment with AE (1 g/kg/twice a day, p.o.) altered
      the reduced glutathione (GSH) levels and antioxidant enzyme activities in several
      organs of the animals. Amount of GSH in uterus was increased (73%) while in
      kidneys it was decreased (23%). Besides, NAD(P)H quinone oxidoreductase 1 (NQO1)
      activity was increased in forestomach (26%) and in liver (64%), while glutathione
      S-transferase activity was decreased in the forestomach (32%) and increased in
      the liver (41%), kidney (35%) and uterus (37%). In preliminary experiments
      targeting the interaction of AE with acetaminophen (600 mg/kg, p.o.), we observed
      augmentation of acetaminophen-induced increase of the plasmatic alanine
      aminotransaminase, aspartate aminotransaminase and lactate dehydrogenase.
      Overall, the results indicate a potential toxic interaction of AE compounds with
      xenobiotics that use the glutathione pathway.

PMID- 25870010
TI  - Shape Fixing via Salt Recrystallization: A Morphology-Controlled Approach To
      Convert Nanostructured Polymer to Carbon Nanomaterial as a Highly Active Catalyst
      for Oxygen Reduction Reaction.
AB  - Herein, we report a "shape fixing via salt recrystallization" method to
      efficiently synthesize nitrogen-doped carbon material with a large number of
      active sites exposed to the three-phase zones, for use as an ORR catalyst. Self
      assembled polyaniline with a 3D network structure was fixed and fully sealed
      inside NaCl via recrystallization of NaCl solution. During pyrolysis, the NaCl
      crystal functions as a fully sealed nanoreactor, which facilitates nitrogen
      incorporation and graphitization. The gasification in such a closed nanoreactor
      creates a large number of pores in the resultant samples. The 3D network
      structure, which is conducive to mass transport and high utilization of active
      sites, was found to have been accurately transferred to the final N-doped carbon
      materials, after dissolution of the NaCl. Use of the invented cathode catalyst in
      a proton exchange membrane fuel cell produces a peak power of 600 mW cm(-2),
      making this among the best nonprecious metal catalysts for the ORR reported so
      far. Furthermore, N-doped carbon materials with a nanotube or nanoshell
      morphology can be realized by the invented method. 

PMID- 25870007
TI  - Vasopressin and disruption of calcium signalling in polycystic kidney disease.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic
      kidney disease and is responsible for 5-10% of cases of end-stage renal disease
      worldwide. ADPKD is characterized by the relentless development and growth of
      cysts, which cause progressive kidney enlargement associated with hypertension,
      pain, reduced quality of life and eventual kidney failure. Mutations in the PKD1
      or PKD2 genes, which encode polycystin-1 (PC1) and polycystin-2 (PC2),
      respectively, cause ADPKD. However, neither the functions of these proteins nor
      the molecular mechanisms of ADPKD pathogenesis are well understood. Here, we
      review the literature that examines how reduced levels of functional PC1 or PC2
      at the primary cilia and/or the endoplasmic reticulum directly disrupts
      intracellular calcium signalling and indirectly disrupts calcium-regulated cAMP
      and purinergic signalling. We propose a hypothetical model in which dysregulated
      metabolism of cAMP and purinergic signalling increases the sensitivity of
      principal cells in collecting ducts and of tubular epithelial cells in the distal
      nephron to the constant tonic action of vasopressin. The resulting magnified
      response to vasopressin further enhances the disruption of calcium signalling
      that is initiated by mutations in PC1 or PC2, and activates downstream signalling
      pathways that cause impaired tubulogenesis, increased cell proliferation,
      increased fluid secretion and interstitial inflammation. 

PMID- 25870012
TI  - Anti-Salmonella Activity of Volatile Compounds of Vietnam Coriander.
AB  - Essential oil derived from the fresh leaves of Polygonum odoratum Lour was tested
      for their effects on a foodborne bacterium Salmonella choleraesuis subsp.
      choleraesuis ATCC 35640 using a broth dilution method. This essential oil showed
      a significant antibacterial activity against S. choleraesuis at the concentration
      of 200 ug/mL. Twenty-five volatile compounds were characterized from this
      essential oil by GC-MS, and aldehyde compounds were found abundant and accounted
      for more than three-fourths of the essential oil. Among the compounds
      characterized, dodecanal (C12 ) was the most abundant (55.5%), followed by
      decanal (C10 ) (11.6%). Both alkanals were effective against S. choleraesuis with
      the minimum growth inhibitory concentration (MIC) and minimum bactericidal
      concentration (MBC) values of 100 ug/mL. The most potent antibacterial activity
      against this bacterium was found with two minor compounds, dodecanol (lauryl
      alcohol) and 2E-dodecenal, both with each MBC of 6.25 ug/mL. Their primary
      antibacterial action against S. choleraesuis provably comes from their ability to
      function as nonionic surface-active agents (surfactants), disrupting the native
      function of integral membrane proteins nonspecifically. Thus, the antibacterial
      activity is mediated by biophysical processes. In the case of 2E-alkenals, a
      biochemical mechanism is also somewhat involved, depending on their alkyl chain
      length.

PMID- 25870011
TI  - Autocrine IL-8 promotes F-actin polymerization and mediate mesenchymal transition
      via ELMO1-NF-kappaB-Snail signaling in glioma.
AB  - Glioma is the most common form of primary malignant brain cancers. Tumor cell
      invasiveness is a critical challenge in the clinical management of glioma
      patients. The invasive biological feature of glioma cell is stimulated by both
      autocrine and paracrine factors including chemokine IL-8. In this study, we
      report that the production of IL-8 is higher in glioma tissues and cells than
      adjacent nontumor tissues (ANT) and normal glial cells. Autocrine IL-8 can
      increase the invasive ability of glioma cells by binding to CXCR1. In addition,
      high expression of IL-8 indicates poor prognosis of glioma patients. Furthermore,
      IL-8 is capable of modulating cell migration and invasion by regulating the
      activation of RAC1 which resulted in cytoskeletal reorganisation in an ELMO1
      dependent manner. Finally, we found that IL-8 could enhance mesenchymal
      transition(MT) of glioma cells by activating ELMO1-NF-kappaB-Snail signaling. Our
      data indicate that IL-8 autocrine is responsible for the invasive phenotype of
      glioma and IL-8 may be a useful prognostic marker for glioma and novel
      therapeutic target for glioma invasion intervention. 

PMID- 25870013
TI  - Blood pressure and disability-free survival among community-dwelling diabetic and
      non-diabetic elderly patients receiving antihypertensive treatment.
AB  - OBJECTIVE: Although many large-scale trials showed efficacies of antihypertensive
      treatment in patients with diabetes mellitus and hypertension for reduction of
      cardiovascular (CV) morbidity/mortality, blood pressure (BP) targets in older
      hypertensive patients with diabetes still represent the object of debate. We
      investigated adequate BP targets with respect to the risk of incident disability
      or mortality in community-dwelling elderly hypertensive patients with and without
      diabetes. METHODS: We analyzed 139 diabetic and 431 non-diabetic patients
      receiving antihypertensive treatment aged 65 years or older. The end-point was
      the composite outcome of first certification for support/care need or mortality.
      Relationships among each of four classes of systolic BP (SBP) or diastolic BP
      (DBP) and the risk of events were estimated using Cox hazards analysis. RESULTS:
      Over 4 years, diabetic patients showed significantly higher rates of all events
      including first certification for support/care need or mortality compared with
      the non-diabetic subjects (29 [20.8%] and 48 [11.1%] cases, unadjusted hazard
      ratio [HR] 1.99, 95% confidence interval (CI) 1.26-3.16, P = 0.003). After
      adjustment for confounding variables, the risk of events was significantly higher
      in non-diabetic subjects with SBP <120 mmHg (HR 3.90, 95% CI 1.32-11.5, P =
      0.014) and SBP >=160 mmHg (HR 3.42, 95% CI 1.22-9.57, P = 0.019), but only those
      with SBP >=160 mmHg (HR 22.8, 95% CI 4.83-118, P < 0.001) in diabetic patients,
      compared with non-diabetic control subjects with baseline SBP of 140-159 mmHg.
      CONCLUSION: These observations showed the critical importance of intensive
      control of SBP to <160 mmHg for disability-free survival in elderly hypertensive
      patients with diabetes mellitus.

PMID- 25870008
TI  - The hallmarks of cancer: relevance to the pathogenesis of polycystic kidney
      disease.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is a progressive inherited
      disorder in which renal tissue is gradually replaced with fluid-filled cysts,
      giving rise to chronic kidney disease (CKD) and progressive loss of renal
      function. ADPKD is also associated with liver ductal cysts, hypertension, chronic
      pain and extra-renal problems such as cerebral aneurysms. Intriguingly, improved
      understanding of the signalling and pathological derangements characteristic of
      ADPKD has revealed marked similarities to those of solid tumours, even though the
      gross presentation of tumours and the greater morbidity and mortality associated
      with tumour invasion and metastasis would initially suggest entirely different
      disease processes. The commonalities between ADPKD and cancer are provocative,
      particularly in the context of recent preclinical and clinical studies of ADPKD
      that have shown promise with drugs that were originally developed for cancer. The
      potential therapeutic benefit of such repurposing has led us to review in detail
      the pathological features of ADPKD through the lens of the defined, classic
      hallmarks of cancer. In addition, we have evaluated features typical of ADPKD,
      and determined whether evidence supports the presence of such features in cancer
      cells. This analysis, which places pathological processes in the context of
      defined signalling pathways and approved signalling inhibitors, highlights
      potential avenues for further research and therapeutic exploitation in both
      diseases. 

PMID- 25870014
TI  - Peripheral nerve sheath tumor invading the nasal cavities of a 6-year-old female
      Pointer dog.

PMID- 25870015
TI  - Preimplantation genetic screening using comprehensive chromosome screening:
      evidence and remaining challenges.

PMID- 25870016
TI  - Reply: Preimplantation genetic screening using comprehensive chromosome
      screening: evidence and remaining challenges.

PMID- 25870017
TI  - Intrapartum sonographic weight estimation.
AB  - PURPOSE: To evaluate the accuracy of intrapartum sonographic weight estimation
      (WE). MATERIALS AND METHODS: This retrospective, cross-sectional study included
      1958 singleton pregnancies. Inclusion criteria were singleton pregnancy with
      cephalic presentation, vaginal delivery and ultrasound examination with complete
      biometric parameters performed on the day of delivery during the latent or active
      phase of labor, and absence of chromosomal or structural anomalies. The accuracy
      of intrapartum WE was compared to a control group of fetuses delivered by primary
      cesarean section at our perinatal center and an ultrasound examination with
      complete biometric parameters performed within 3 days before delivery (n = 392).
      Otherwise, the same inclusion criteria as in the study group were applied. The
      accuracy of WE was compared between five commonly applied formulas using means of
      percentage errors (MPE), medians of absolute percentage errors (MAPE), and
      proportions of estimates within 10 % of actual birth weight. RESULTS: In the
      whole study group, all equations showed a systematic underestimation of fetal
      weight (negative MPEs). Overall, best MAPE and MPE values were found with the
      Hadlock II formula, using BPD, AC and FL as biometric parameters (Hadlock II,
      MPE: -1.28; MAPE: 6.52). MPEs differed significantly between WE in the study and
      control group for all evaluated formulas: in the control group, either no
      systematic error (Hadlock III, IV and V) or a significant overestimation (Hadlock
      I, II) was found. Regarding MAPEs, application of the Hadlock III (HC, AC, FL)
      and V (AC) formula resulted in significant lower values in the control group
      (Hadlock III, MAPE: 7.48 vs. 5.95, p = 0.0008 and Hadlock V, MAPE: 8.79 vs. 7.52,
      p = 0.0085). No significant differences were found for the other equations.
      CONCLUSIONS: A systematic underestimation of fetal weight has to be taken into
      account in sonographic WE performed intrapartum. Overall, the best results can be
      achieved with WE formulas using the BPD as the only head measurement.

PMID- 25870018
TI  - Food deprivation reduces and leptin increases the amplitude of an active sensory
      and communication signal in a weakly electric fish.
AB  - Energetic demands of social communication signals can constrain signal duration,
      repetition, and magnitude. The metabolic costs of communication signals are
      further magnified when they are coupled to active sensory systems that require
      constant signal generation. Under such circumstances, metabolic stress incurs
      additional risk because energy shortfalls could degrade sensory system
      performance as well as the social functions of the communication signal. The
      weakly electric fish Eigenmannia virescens generates electric organ discharges
      (EODs) that serve as both active sensory and communication signals. These EODs
      are maintained at steady frequencies of 200-600Hz throughout the lifespan, and
      thus represent a substantial metabolic investment. We investigated the effects of
      metabolic stress (food deprivation) on EOD amplitude (EODa) and EOD frequency
      (EODf) in E. virescens and found that only EODa decreases during food deprivation
      and recovers after restoration of feeding. Cortisol did not alter EODa under any
      conditions, and plasma cortisol levels were not changed by food deprivation. Both
      melanocortin hormones and social challenges caused transient EODa increases in
      both food-deprived and well-fed fish. Intramuscular injections of leptin
      increased EODa in food-deprived fish but not well-fed fish, identifying leptin as
      a novel regulator of EODa and suggesting that leptin mediates EODa responses to
      metabolic stress. The sensitivity of EODa to dietary energy availability likely
      arises because of the extreme energetic costs of EOD production in E. virescens
      and also could reflect reproductive strategies of iteroparous species that reduce
      social signaling and reproduction during periods of stress to later resume
      reproductive efforts when conditions improve. 

PMID- 25870019
TI  - Effects of uterine and lactational exposure to di-(2-ethylhexyl) phthalate on
      spatial memory and NMDA receptor of hippocampus in mice.
AB  - Di-(2-ethylhexyl) phthalate (DEHP) is an environmental endocrine disrupter.
      Currently, little is known about neurodevelopmental toxicity of DEHP in wildlife
      and humans. The present study investigated the effects of DEHP, focusing on the
      changes in the behavior of offspring mice at the ages of 6 and 12w, respectively,
      following utero and lactational exposure to DEHP (10, 50, and 200mg/kg/d) from
      gestation day 7 through postnatal day 21. The results of open field tasks showed
      that DEHP increased the grooming of males at age 6w and females at age 12w but
      decreased the frequency of rearing of 6-w-old females and the number of grid
      crossings of 12-w-old females. In the Morris water maze task, 50 and 200mg/kg/d
      DEHP significantly prolonged the time of searching the hidden platform in water
      maze and reduced the time staying in the target quadrant during a probe trial of
      6-w-old male mice, but not of 6-w-old females nor 12-w-old mice of both sexes,
      suggesting an impaired spatial learning and memory among younger males after
      perinatal exposure to DEHP. Western blot analyses further showed that DEHP at 50
      and 200mg/kg/d decreased the levels of the N-methyl-d-aspartic acid (NMDA)
      receptor subunits NR1 and NR2B in the hippocampus of 6-w-old males. These results
      suggest that uterine and lactational exposure to low doses of DEHP sex
      specifically impacted behaviors, including locomotion activity and spatial
      memory, via the concomitant inhibition of the NMDA receptor of the hippocampus in
      offspring mice. 

PMID- 25870020
TI  - Influence of mate preference and laying order on maternal allocation in a
      monogamous parrot species with extreme hatching asynchrony.
AB  - It is well established that in many avian species, prenatal maternal resource
      allocation varies both between and within clutches and may affect offspring
      fitness. Differential allocation of maternal resources, in terms of egg weight
      and yolk composition, may therefore allow the female to adjust brood reduction
      and to fine-tune reproductive investment in accordance with the expected fitness
      returns. The adaptive value of such maternal resource allocation is thought to be
      context-dependent as well as species-specific. We investigated the effects of
      female preference for her mate on the allocation of prenatal maternal resources
      in the budgerigar, Melopsittacus undulatus, a monogamous species of parrot that
      shows an extreme hatching asynchrony. We assessed mate preferences in a two-way
      preference test and allowed females two breeding rounds: one with the preferred
      and one with the non-preferred partner. We found no effect of preference on
      either latency to lay or clutch size, but females mated with the preferred
      partner laid eggs that contained significantly more yolk. Their eggs also
      contained significantly more androstenedione but not testosterone. Our results
      suggest that in this species, female preference may influence maternal resource
      allocation, and that the functional roles of each androgen in the yolk should be
      considered separately. In addition, we found a significant effect of laying order
      on egg and yolk weight as well as on yolk testosterone and androstenedione
      levels. These measures, however, did not change linearly with the laying order
      and render it unlikely that female budgerigars compensate for the extreme
      hatching asynchrony by adjusting within-clutch allocation of prenatal maternal
      resources. 

PMID- 25870021
TI  - Urinary C-peptide levels in male bonobos (Pan paniscus) are related to party size
      and rank but not to mate competition.
AB  - Within- and between-species variation in male mating strategies has been
      attributed to a multitude of factors including male competitive ability and the
      distribution of fertile females across space and time. Differences in energy
      balance across and within males allow for the identification of some of the trade
      offs associated with certain social and mating strategies. Bonobos live in groups
      with a high degree of fission-fusion dynamics, there is co-dominance between the
      sexes and a linear dominance hierarchy among males. Males compete over access to
      females, breeding is aseasonal, and females exhibit sexual swellings over
      extended time periods. In this study we use urinary C-peptide (UCP) levels in
      male bonobos (Pan paniscus) obtained from 260 urine samples from a wild bonobo
      community, to quantify male energy balance during mate competition and levels of
      gregariousness in the species. Although high ranking males are more aggressive,
      spend more time in proximity to maximally tumescent females, and have higher
      mating frequencies, we found no indication that mate guarding or mate competition
      affected male energy balance. Our results showed a positive correlation between
      monthly mean UCP levels and mean party size. When traveling in large parties,
      high ranking males had higher UCP levels than those of the low ranking males.
      These results support the hypothesis that patterns of fission-fusion dynamics in
      bonobos are either linked to energy availability in the environment or to the
      energetic costs of foraging. The finding of a rank-bias in UCP levels in larger
      parties could also reflect an increase in contest competition among males over
      access to food. 

PMID- 25870022
TI  - Experience of a serious life event increases the risk for childhood type 1
      diabetes: the ABIS population-based prospective cohort study.
AB  - AIMS/HYPOTHESIS: The aim of this study was to prospectively investigate whether
      psychological stress during childhood may be a risk factor for manifest type 1
      diabetes. METHODS: The All Babies In Southeast Sweden (ABIS) study invited all
      families with babies born between 1 October 1997 and 30 September 1999 in
      southeast Sweden to participate. Our study subsample includes 10,495 participants
      in at least one of the data collections at 2-3, 5-6, 8 and 10-13 years of age not
      yet diagnosed with type 1 diabetes at inclusion; 58 children were subsequently
      diagnosed. Age at diagnosis was obtained from the national register SweDiabKids
      in 2012. Family psychological stress was measured via questionnaires given to the
      parents assessing serious life events, parenting stress, parental worries and the
      parent's social support. RESULTS: Childhood experience of a serious life event
      was associated with a higher risk of future diagnosis of type 1 diabetes (HR 3.0
      [95% CI 1.6, 5.6], p = 0.001) after adjusting for heredity of type 1 diabetes and
      age at entry into the study. The result was still valid when controlling for
      heredity of type 2 diabetes, size for gestational age, the parents' education
      level and whether the mother worked at least 50% of full time before the child's
      birth (HR 2.8 [95% CI 1.5, 5.4], p = 0.002), and also when childhood BMI was
      added to the model (HR 5.0 [95% CI 2.3, 10.7], p < 0.001).
      CONCLUSIONS/INTERPRETATION: This first prospective study concluded that
      experience of a serious life event in childhood may be a risk factor for manifest
      type 1 diabetes.

PMID- 25870024
TI  - Concerns About Falling in Parkinson's Disease: Associations with Disabilities and
      Personal and Environmental Factors.
AB  - BACKGROUND: Fear of falling can be conceptualized in different ways, e.g., as
      concerns about falling or low fall-related self-efficacy. It is common in people
      with Parkinson's disease (PD), and there is growing knowledge about its
      contributing factors. However, previous multivariate studies have mainly focused
      on fear of falling in relation to PD-related disabilities, and less is known
      about the associations between fear of falling and personal and environmental
      factors. OBJECTIVE: To identify explanatory factors of concerns about falling in
      people with PD by focusing on personal and environmental factors as well as PD
      related disabilities. METHODS: Data were collected from 241 persons with PD (39%
      women, median age 70 years, PD duration 8 years). Concerns about falling
      (assessed with the Falls Efficacy Scale-International, FES-I; categorized into
      low, moderate, or high concerns) were used as the dependent variable in a
      multivariate ordinal regression analysis. Personal factors, environmental factors
      and PD-related disabilities constituted independent variables. RESULTS: Low,
      moderate and high concerns about falling were reported by 29% , 24% and 47% of
      the participants, respectively. Walking difficulties, orthostatism, motor
      symptoms, age, and fatigue (presented in order of importance) were significant (p
      <  0.05) explanatory factors of concerns about falling. CONCLUSIONS: Several
      factors significantly explained concerns about falling in people with PD. Walking
      difficulties was by far the strongest explanatory factor. This suggests that
      minimizing walking difficulties should be a primary target when aiming at
      reducing concerns about falling in people with PD.

PMID- 25870023
TI  - Dysregulation of muscle glycogen synthase in recovery from exercise in type 2
      diabetes.
AB  - AIMS/HYPOTHESIS: Insulin and exercise stimulate skeletal muscle glycogen synthase
      (GS) activity by dephosphorylation and changes in kinetic properties. The aim of
      this study was to investigate the effects of insulin, exercise and post-exercise
      insulin stimulation on GS phosphorylation, activity and substrate affinity in
      obesity and type 2 diabetes. METHODS: Obese men with type 2 diabetes (n = 13) and
      weight-matched controls (n = 14) underwent euglycaemic-hyperinsulinaemic clamps
      in the rested state and 3 h after 60 min of cycling (70% maximal pulmonary oxygen
      uptake [VO2max]). Biopsies from vastus lateralis muscle were obtained before and
      after clamps, and before and immediately after exercise. RESULTS: Insulin
      stimulated glucose uptake was lower in diabetic patients vs obese controls with
      or without prior exercise. Post exercise, glucose partitioning shifted away from
      oxidation and towards storage in both groups. Insulin and, more potently,
      exercise increased GS activity (fractional velocity [FV]) and substrate affinity
      in both groups. Both stimuli caused dephosphorylation of GS at sites 3a + 3b,
      with exercise additionally decreasing phosphorylation at sites 2 + 2a. In both
      groups, changes in GS activity, substrate affinity and dephosphorylation at sites
      3a + 3b by exercise were sustained 3 h post exercise and further enhanced by
      insulin. Post exercise, reduced GS activity and substrate affinity as well as
      increased phosphorylation at sites 2 + 2a were found in diabetic patients vs
      obese controls. CONCLUSIONS/INTERPRETATION: Exercise-induced activation of muscle
      GS in obesity and type 2 diabetes involves dephosphorylation of GS at sites 3a +
      3b and 2 + 2a and enhanced substrate affinity, which is likely to facilitate
      glucose partitioning towards storage. Lower GS activity and increased
      phosphorylation at sites 2 + 2a in type 2 diabetes in the recovery period imply
      an impaired response to exercise.

PMID- 25870025
TI  - Apathy and Impulse Control Disorders: Yin & Yang of Dopamine Dependent Behaviors.
AB  - Neuropsychiatric symptoms are common non-motor symptoms in Parkinson's disease
      (PD). Apathy and impulse control disorders (ICD) are two opposite motivational
      expressions of a continuous behavioural spectrum involving hypo- and
      hyperdopaminergia. Both syndromes share pathological (decreased vs increased)
      dopamine receptor stimulation states. Apathy belongs to the spectrum of
      hypodopaminergic symptoms together with anhedonia, anxiety and depression. Apathy
      is a key symptom of PD which worsens with disease progression. Animal models,
      imaging and pharmacological studies concur in pointing out dopaminergic
      denervation in the aetiology of parkinsonian apathy with a cardinal role of
      decreased tonic D2/D3 receptor stimulation. ICDs are part of the
      hyperdopaminergic behavioural spectrum, which also includes punding, and dopamine
      dysregulation syndrome (DDS), which are all related to non-physiological
      dopaminergic stimulation induced by antiparkinsonian drugs. According to clinical
      data tonic D2/D3 receptor stimulation can be sufficient to induce ICDs. Clinical
      observations in drug addiction and PD as well as data from studies in dopamine
      depleted rodents provide hints allowing to argue that both pulsatile D1 and D2
      receptor stimulation and the severity of dopaminergic denervation are risk
      factors to develop punding behavior and DDS. Imaging studies have shown that the
      brain structures involved in drug addiction are also involved in
      hyperdopaminergic behaviours with increase of bottom-up appetitive drive and
      decrease in prefrontal top down behavioural control. 

PMID- 25870026
TI  - Variations of the blood gas levels and thermodilutional parameters during ICP
      monitoring after severe head trauma in children.
AB  - PURPOSE: The purpose of this study was to define, in children following head
      trauma and GSC <= 8, at which level of intracranial pressure (ICP), the
      thermodilutional, and gas analytic parameters implicated in secondary cerebral
      insults shows initial changes. METHODS: We enrolled in the study 56 patients: 30
      males and 26 females, mean age 71 +/- 52 months. In all children, volumetric
      hemodynamic and blood gas parameters were monitored following initial
      resuscitation and every 4 h thereafter or whenever a hemodynamic deterioration
      was suspected. During the cumulative hospital stay, a total of 1050 sets of
      measurements were done. All parameters were stratified in seven groups according
      to ICP (group A1 = 0-5 mmHg, group A2 = 6-10 mmHg, group A3 = 11-15 mmHg, group
      A4 16-20 mmHg, group A5 21-25 mmHg, group A6 26-30 mmHg, group A7 >31 mmHg).
      RESULTS: Mean values of jugular oxygen saturation (SJO2), jugular oxygen partial
      pressure (PJO2), extravascular lung water (EVLWi), pulmonary vascular
      permeability (PVPi), fluid overload (FO), and cerebral extraction of oxygen
      (CEO2) vary significantly from A3 (11-15 mmHg) to A4 (16-20 mmHg). They relate to
      ICP in a four-parameter sigmoidal function (4PS function with: r(2) = 0.90),
      inflection point of 15 mmHg of ICP, and a maximum curvature point on the left
      horizontal asymptote at 13 mmHg of ICP. CONCLUSIONS: Mean values of SJO2, PJO2,
      EVLWi, PVPi, FO, and CEO2 become pathologic at 15 mmHg of ICP; however, the curve
      turns steeper at 13 mmHg, possibly a warning level in children for the
      development of post head trauma secondary insult.

PMID- 25870027
TI  - Factors affecting infection development after meningomyelocele repair in newborns
      and the efficacy of antibiotic prophylaxis.
AB  - AIM: The purpose of this study was to evaluate the clinical and surgical
      variables that may be associated with wound infection and
      meningitis/ventriculoperitoneal (VP) shunt infection in newborns diagnosed with
      meningomyelocele (MMC), as well as the efficacy of antibiotic prophylaxis in
      reducing these complications. MATERIAL AND METHODS: The data of 91 neonates
      diagnosed with MMC, who underwent surgical intervention between May 2012 and
      December 2014, were retrospectively evaluated. Multivariant logistic regression
      analysis was used to determine the possible clinical and neurosurgical variables
      associated with meningitis/VP shunt infection and surgical wound infection.
      Spearman's test was performed for the correlation analysis. RESULTS: Following
      MMC closure, of the 91 neonates, 18 (16.4%) developed meningitis/shunt infection
      and 12 (11%) developed surgical wound infection. The operation time was not a
      significant independent risk factor for the development of meningitis (RR 0.618
      [0.199-1.922], p = 0.406). Open neural placodes that were not covered by any
      pseudomembrane (myeloschisis), external ventricular drainage (EVD) use, and flap
      transposition were determined as significant relative risk factors for the
      development of meningitis (RR 8.655 [2.329-32.157], p = 0.001; RR 9.404 [1.183
      74.743], p = 0.034; RR 8.125 [2.496-26.448], p = 0.001; and RR 3.150 [1.963
      10.308], p = 0.048, respectively). Deep surgical wound infection was not
      correlated with the operation time or wound surface area. However, there was an
      intermediate but very significant positive correlation between meningitis and
      cerebrospinal fluid (CSF) leakage, length of hospitalization, and flap
      transposition (r = 0.377, 0.420, 0.357, and 0.503, respectively; for all values,
      p < 0.001). CONCLUSIONS: There was no association between MMC closure and
      development of infection. Since it carries a high risk for the development of
      meningitis, the EVD system should be avoided unless necessary. Routine
      prophylactic antibiotic use did not reduce the infection risk in MMC repair
      surgery. Thus, antibiotics should not be used if there are no risk factors
      predisposing to infection.

PMID- 25870028
TI  - Possible Legal Barriers for PCP Access to Mental Health Treatment Records.
AB  - Provider and payer groups have endorsed the goal of improving the integration of
      primary care and behavioral health across a variety of programs and settings.
      There is an interest in sharing patients' medical information, a goal that is
      permissible within HIPAA, but there are concerns about more restrictive state
      medical privacy laws. This article assesses whether a substantial number of state
      medical privacy laws are, or could be interpreted to be, more restrictive than
      HIPAA. Preliminary investigation found that in almost one third of the states
      (including large-population states such as Florida, Georgia, Massachusetts, New
      York, and Texas), primary care physicians (PCPs) may have difficulty accessing
      mental health treatment records without the patient's (or his/her
      guardian/conservator's) written consent. If a comprehensive legal analysis
      supports this conclusion, then those advocating integration of behavioral and
      primary care may need to consider seeking appropriate state legislative
      solutions. 

PMID- 25870029
TI  - Nonideal effects in electroacoustics of solutions of charged particles: combined
      experimental and theoretical analysis from simple electrolytes to small
      nanoparticles.
AB  - The electric signal induced by an ultrasonic wave in aqueous solutions of charged
      species is measured and analyzed. A device is developed which measures the raw
      induced electric signal for small sample volumes (few milliliters) and without
      any preceding calibration. The potential difference generated between two
      identical electrodes, called the ionic vibration potential (IVP), is thus easily
      deduced. In parallel, a theory for the IVP is built based on a robust analytical
      theory already used successfully to account for other transport coefficients in
      electrolyte solutions. From the analysis of the IVP measured for several aqueous
      electrolyte solutions, which are well-defined model systems for this technique,
      we explain and validate the different contributions to the signal. In particular,
      the non-ideal effects at high concentrations are thoroughly understood. A first
      step towards colloidal systems is presented by the analysis of the signal in
      solutions of a polyoxometallate salt, opening the possibility of determinations
      of reliable electrophoretic mobilities in dispersions of nanoobjects. 

PMID- 25870030
TI  - Red cell alloimmunisation in regularly transfused beta thalassemia patients in
      Pakistan.
AB  - BACKGROUND: In Pakistan routine blood group typing of thalassemia patients
      identifies ABO and Rh(D) antigens only. Therefore, other antigen
      incompatibilities between blood donor and blood recipient may cause
      alloimmunisation. OBJECTIVE: The aim of this study was to estimate the frequency
      of alloimmunisation and to evaluate the risk factors associated with its
      development in beta (beta)-thalassemia patients receiving regular blood
      transfusions. MATERIALS AND METHODS: In total 162 beta thalassemia patients were
      included in this study. An extended red cell antigen panel was performed to
      detect antibodies. Patients received red cell concentrates, which were matched
      for ABO and Rh(D) antigens. Clinical and laboratory data were collected and
      analysed to estimate the frequency of alloantibodies and the factors influencing
      immunisation in patients on regular blood transfusion. RESULTS: The median age of
      patients was 6.7 (range: 0.5-25) years. A total of 14 (8.6%) patients developed
      alloantibodies against red cell antigens. The most frequently occurring
      alloantibodies was anti-E (2.5%), anti-K (1.8%), anti-e (1.2%) and anti-D (0.6%).
      Five (3.1%) patients developed more than one red blood cell (RBC) alloantibody.
      Age at first transfusion in alloimmunised patients was 1.22 +/- 0.87 years. The
      frequency of blood transfusion in alloimmunised patients was 23 +/- 8.81 days and
      in those without alloimmunisation was 31.8 +/- 16 days (p = 0.02). Logistic
      regression analysis showed no independent risk factor associated with
      alloimmunisation. CONCLUSION: The frequency of transfusion was increased in
      patients who developed alloantibodies. Typing patients and donors to match for Rh
      and Kell antigens would prevent more than 90% of RBC alloantibodies and reduce
      the frequency of transfusion in thalassemia patients.

PMID- 25870031
TI  - Self-emulsifying drug delivery system developed by the HLB-RSM approach:
      Characterization by transmission electron microscopy and pharmacokinetic study.
AB  - Recently, we developed a new approach to rationalize an optimized design for self
      emulsifying drug delivery system (SEDDS) by introducing the HLB and the response
      surface as determinant factors in SEDDS development. The aim of this current
      paper is to assess the suitability of this HLB-RSM approach to enhance the oral
      bioavailability of BCS class II compounds using fenofibrate as drug model. Eight
      SEDDS formulations (I->VIII) were pre-selected regarding their self
      emulsification capacity and their effect on increasing in vitro drug release.
      They were firstly evaluated for their thermodynamic stability and zeta potential.
      Unstable SEDDS were discarded meanwhile the structural morphology of the stable
      ones (I, VI and VIII) was characterized using transmission electron microscopy
      (TEM). A pharmacokinetic study was then undertaken on male BALB/cJRj mices. The
      in vivo results showed a significant increase of fenofibrate absorption for all
      the three stable SEDDS formulations compared to the commercialized form,
      (LIPANTHYL micronized((r)) (p<0.05)). The highest enhancement was recorded for
      SEDDS I, where AUC and Cmax values respectively increased by 2 and 4.4 folds.
      This justifies the fact that HLB-RSM approach could be considered as a promising
      method for the development of efficient and highly stable SEDDS aiming to
      increase the poor bioavailability of BCS class II molecules.

PMID- 25870035
TI  - Dramatic improvement of membrane performance for microalgae harvesting with a
      simple bubble-generator plate.
AB  - To overcome fouling issue in membrane-based algae harvesting and thus make an
      otherwise promising harvesting option more competitive, a bubble-generator plate
      was developed. According to computational fluid dynamics analysis, the plate
      generated substantial hydrodynamic power in terms of high pressure, velocity, and
      shear stress. When installed in a membrane filtration system with membranes of
      different surface and structural characteristics (one prepared by the phase
      inversion method, and a commercial one) the bubble-generator was indeed effective
      in reducing fouling. Without the plate, the much cheaper homemade membrane had
      the similar performance as the commercial one. Use of the bubble-generator
      considerably improved the performance of both membranes, and revealed a valuable
      synergy with the asymmetrical structure of the homemade membrane. This result
      clearly showed that the ever-problematic fouling could be mitigated in a rather
      easy manner, and in so doing, that membrane technology could indeed become a
      practical option for algae harvesting. 

PMID- 25870034
TI  - Cancer-related search for meaning increases willingness to participate in
      mindfulness-based stress reduction.
AB  - OBJECTIVE: A cancer diagnosis can prompt an examination and reevaluation of
      life's meaning, purpose, and priorities. There is evidence that mindfulness-based
      stress reduction (MBSR) may help facilitate the meaning-making process. This
      study examined the influence of meaning in life on willingness to participate
      (WTP) in MBSR and identified factors associated with the search for and/or
      presence of meaning. METHODS: A cross-sectional survey study of 300 patients
      undergoing radiation therapy was conducted. WTP in MBSR was dichotomized into
      yes/no by asking, "Would you participate in an MBSR program if it was offered at
      the cancer center?" The search for, and the presence of, meaning were assessed
      using the Meaning in Life Questionnaire. RESULTS: Eighty patients (27%) indicated
      WTP in MBSR. In a multivariate logistic regression model, search for meaning was
      the only significant predictor of WTP in MBSR (adjusted odds ratio [AOR] =1.04, P
      <= .001, 95% CI = 1.01-1.08). Identifying as non-white (adjusted beta = 4.62; 95%
      CI = 2.22-7.02; P < .001), and reporting subclinical (adjusted beta = 3.59; 95%
      CI = 0.84-6.34; P = .01) or clinical levels (adjusted beta = 5.52; 95% CI = 2.41
      8.63; P = .001) of anxiety were the strongest predictors of search for meaning.
      CONCLUSION: Our study indicates that patients searching for meaning are receptive
      to MBSR. Nonwhite patients and those experiencing high levels of anxiety are most
      likely to endorse a search for meaning. Future research is needed to understand
      how best to support patients who are searching for meaning and remove barriers to
      evidence-based programs like MBSR.

PMID- 25870032
TI  - Narrow therapeutic index drugs: a clinical pharmacological consideration to
      flecainide.
AB  - PURPOSE: The therapeutic index (TI) is the range of doses at which a medication
      is effective without unacceptable adverse events. Drugs with a narrow TI (NTIDs)
      have a narrow window between their effective doses and those at which they
      produce adverse toxic effects. Generic drugs may be substituted for brand-name
      drugs provided that they meet the recommended bioequivalence (BE) limits.
      However, an appropriate range of BE for NTIDs is essential to define due to the
      potential for ineffectiveness or adverse events. Flecainide is an antiarrhythmic
      agent that has the potential to be considered an NTID. This review aims to
      evaluate the literature surrounding guidelines on generic substitution for NTIDs
      and to evaluate the evidence for flecainide to be considered an NTID. METHODS: A
      review of recommendations from various regulatory authorities regarding BE and
      NTIDs, and publications regarding the NTID characteristics of flecainide, was
      carried out. RESULTS: Regulatory authorities generally recommend reduced BE
      limits for NTIDs. Some, but not all, regulatory authorities specify flecainide as
      an NTID. The literature review demonstrated that flecainide displays NTID
      characteristics including a steep drug dose-response relationship for safety and
      efficacy, a need for therapeutic drug monitoring of pharmacokinetic (PK) or
      pharmacodynamics measures and intra-subject variability in its PK properties.
      CONCLUSIONS: There is much evidence for flecainide to be considered an NTID based
      on both preclinical and clinical data. A clear understanding of the potential of
      proarrhythmic effects or lack of efficacy, careful patient selection and regular
      monitoring are essential for the safe and rational administration of flecainide.

PMID- 25870036
TI  - Measuring Biomarker Progress.
AB  - A biomarker has been defined as "a characteristic that is objectively measured
      and evaluated as an indicator of normal biologic processes, pathogenic process,
      or pharmacologic responses to a therapeutic intervention." This comprehensive
      definition of biomarkers arose from the April 1999 US Food and Drug
      Administration (FDA)/National Institutes of Health consensus conference on
      "Biomarkers and Surrogate Endpoints: Advancing Clinical Research and
      Applications," and emphasized that biomarkers are medical measurements, including
      physiological measurements, blood tests, molecular analyses of biopsies, genetic
      or metabolic data, and measurements from images. Research on biomarkers-organized
      and propelled by this definition-has skyrocketed, with over 200,000 PubMed
      citations in the last five years. 

PMID- 25870037
TI  - Kaempferol enhances the suppressive function of Treg cells by inhibiting FOXP3
      phosphorylation.
AB  - Kaempferol is a natural flavonoid found in many vegetables and fruits.
      Epidemiologic studies have described that Kaempferol intake could reduce risk of
      cancer, especially lung, gastric, pancreatic and ovarian cancers. Recent studies
      have shown that Kaempferol could also be beneficial to the body to defend against
      inflammation, and infection by bacteria and viruses; however, the molecular
      mechanism of its immunoregulatory function remains largely unknown. Through
      screening a small molecule library of traditional Chinese medicine (TCM), we
      identified that Kaempferol could enhance the suppressive function of regulatory T
      cells (Tregs). Kaempferol was found to increase FOXP3 expression level in Treg
      cells and prevent pathological symptoms of collagen-induced arthritis in a rat
      animal model. Kaempferol could also reduce PIM1-mediated FOXP3 phosphorylation at
      S422. Our study reveals a molecular mechanism that underlies the anti
      inflammatory action of Kaempferol for the prevention and treatment of
      inflammatory diseases such as rheumatoid arthritis, systemic lupus erythematosus,
      and ankylosing spondylitis. 

PMID- 25870039
TI  - An innovative nursing approach to caring for an obstetric patient with rape
      trauma syndrome.
AB  - Rape trauma syndrome (RTS) is a posttraumatic stress disorder that can be
      triggered by routine procedures experienced during childbirth. An explanation of
      the signs and symptoms of RTS is provided, including how to avoid
      retraumatization during intrapartum care. A case report is presented from a
      provider perspective to illustrate the seriousness of this disorder and the
      importance of delivering respectful care. A new approach to obstetric routines is
      warranted to avoid further traumatizing the woman with RTS. 

PMID- 25870040
TI  - The academic forensic pathologist : An endangered species?

PMID- 25870038
TI  - Functional interactions among members of the miR-17-92 cluster in lymphocyte
      development, differentiation and malignant transformation.
AB  - The miR-17-92 cluster is a prototypical example of a polycistronic miRNA gene.
      Recently, miR-17-92 has emerged as a pleiotropic regulator in immune system. Its
      loss or deregulation leads to defects in lymphocyte development and response, and
      lymphoma development. Although the six individual miRNAs of the cluster are
      expressed together from the same primary transcript, their relative abundance,
      functional contributions and interactions vary in different cellular contexts. 

PMID- 25870041
TI  - Forensic archaeology and anthropology : An Australian perspective.
AB  - Forensic archaeology is an extremely powerful investigative discipline and, in
      combination with forensic anthropology, can provide a wealth of evidentiary
      information to police investigators and the forensic community. The re-emergence
      of forensic archaeology and anthropology within Australia relies on its
      diversification and cooperation with established forensic medical organizations,
      law enforcement forensic service divisions, and national forensic boards. This
      presents a unique opportunity to develop a new multidisciplinary approach to
      forensic archaeology/anthropology within Australia as we hold a unique set of
      environmental, social, and cultural conditions that diverge from overseas models
      and require different methodological approaches. In the current world political
      climate, more forensic techniques are being applied at scenes of mass disasters,
      genocide, and terrorism. This provides Australian forensic
      archaeology/anthropology with a unique opportunity to develop multidisciplinary
      models with contributions from psychological profiling, ballistics,
      sociopolitics, cultural anthropology, mortuary technicians, post-blast analysis,
      fire analysis, and other disciplines from the world of forensic science. 

PMID- 25870042
TI  - Computerized forensic facial reconstruction : A review of current systems.
AB  - Forensic investigations frequently utilize facial reconstructions/approximations
      to stimulate recognition and identification. Over the past 25 years, many
      computer-based systems have been developed, and with the recent rapid advances in
      medical imaging and computer technology, the current systems claim high levels of
      efficiency, objectivity, and flexibility. The history of computerized facial
      approximation/reconstruction is presented, along with a discussion of the
      advantages and disadvantages of the technologies. Evaluation of the accuracy and
      reproducibility of these new systems is critical for the future of computerized
      facial reconstruction/approximation to become accepted by the wider forensic
      science field. In addition, constant re-evaluation and assessment will promote
      further improvement and increase reliability. 

PMID- 25870043
TI  - Is SIDS associated with sleep? : A report of six cases demonstrating difficulty
      in this determination.
AB  - Epidemiological studies suggest an important association of sudden infant death
      syndrome (SIDS) with sleep. Because these deaths are very rarely observed, this
      association is difficult to confirm. When nearby caretakers hear noises
      suggesting that some infants are awake before their deaths from SIDS, this
      determination may be even more difficult. We report six cases illustrating the
      difficulty in determining the sleep status of SIDS infants immediately prior to
      their deaths. A retrospective analysis was undertaken of the San Diego SIDS/SUDC
      Research Project database and the new SIDS definition proposed at the January
      2004 conference in San Diego, California was applied. The circumstances
      surrounding the deaths of six infants led nearby caretakers to speculate that all
      were awake before dying. However, careful analyses suggest that all but one
      infant were actually sleeping before their deaths. This study strengthens the
      association of SIDS with sleep and emphasizes the importance of very detailed
      evaluation of the circumstances of death in all cases of sudden infant death. The
      use of the recently stratified definition for SIDS as well as the new category of
      unclassified sudden infant death (USID) is recommended. 

PMID- 25870044
TI  - Exploring the effect of the occurrence of sound on force applied by the ear when
      listening at a surface.
AB  - In this article, we explore the effect of the occurrence of a target sound on the
      force that is applied by the ear when listening at a surface because differences
      in applied force induce variation in carprints of a single ear. Forty two
      subjects each listened four times at a surface. During two of these listening
      efforts there was silence. While the subjects were listening, we measured the
      amount of force that was applied to the surface. To explore the effect of the
      occurrence of a target sound upon applied force, we applied a mixed model
      analysis of variance. The force applied by the ear appeared to be uncorrelated to
      presence or absence of a target sound. This lack of association appeared not to
      be the result of potential confounders. Only repetition (i.e., the position of a
      listening effort in the series of four), appeared to significantly affect applied
      force; this force being generally lower during a first listening effort. 

PMID- 25870045
TI  - High-grade decubitus ulcers in the elderly : A Postmortem Case-Control Study of
      Risk Factors.
AB  - Some elderly persons develop high-grade decubitus ulcers, whereas others with
      comparable risk factors do not. In Germany, forensic pathologists are
      increasingly confronted by situations that necessitate an expert opinion on
      whether prevention of decubitus ulcers has been neglected in cases of suspected
      malpractice. This investigation was carried out in an attempt to identify risk
      factors for decubitus ulcers. We performed a postmortem case-control study in
      elderly persons who developed high-grade decubitus ulcers from 6 months to 14
      days before death. Deceased with decubitus ulcers graded 3 or higher and controls
      at comparable risk were examined before cremation. After written informed consent
      had been obtained from the nearest living relatives, all available nursing and
      medical records of the deceased were thoroughly evaluated. Decubitus ulcer cases
      and controls were matched according to age, gender, immobility, and cachexia. One
      hundred cases of decubitus ulcers with 71 grade 3 decubitus ulcers and 29 grade 4
      decubitus ulcers were compared with 100 controls with 27 decubitus ulcers graded
      2 or lower and the maximal risk as assessed by the Norton scale. The mean age was
      86 years, 80% were females, 86% were bedridden, and cachexia was found in 66%.
      The individuals with decubitus ulcers were more often severely disabled, had more
      immobility of joints, and were more often under treatment with antidepressive
      and/or sedative drugs (e.g., opioid analgesies, neurolepties, benzodiazepines).
      Patients' impaired ability or unwillingness to comply or cooperate with
      preventive and therapeutic measures was more often recorded in cases of decubitus
      than in the control group. There was no evidence that supplementary nutrition or
      use of preventive pressure relief and protective devices differed between the
      decubitus cases and the controls. 

PMID- 25870046
TI  - Studies of adipocere using attenuated total reflectance infrared spectroscopy.
AB  - Attenuated total reflectance (ATR) infrared spectroscopy has been used to
      characterize pig adipocere formation. The compositions of adipocere samples
      obtained by burial of pig adipose tissue in soil and in mock coffins were
      compared with that of the original adipose tissue using this technique. The ART
      spectra show that bands resulting from triglyceride and fatty acid C=O stretching
      are particularly useful for monitoring the changes in adipocere formation. The
      technique is able to be used to investigate how the burial environment affects
      the rate of adipocere formation and supports the results of earlier gas
      chromatograph and mass spectrometer and diffuse reflectance infrared studies. ATR
      spectroscopy has also been demonstrated to have the advantage of convenient
      sample preparation. 

PMID- 25870048
TI  - Note from the editors.

PMID- 25870047
TI  - Tangential gunshot wound with MagSafe ammunition.
AB  - MagSafe ammunition is a type of unconventional prefragmented ammunition. A fatal
      tangential gunshot wound involving MagSafe ammunition is presented. The
      ammunition and wound characteristics are discussed. 

PMID- 25870049
TI  - Characteristic acquired features of indigenous australians that may be observed
      in forensic practice.
AB  - Australian aboriginal people who are living in traditional groups often have a
      variety of characteristic acquired features that distinguish them from those who
      have been resident in less traditional communities. These features include
      particular forms of scarification, tooth avulsion, and subincision of the penis.
      Skeletonized remains may also show acquired features such as marked dental
      attrition, parry fractures, and squatting notches of the long bones. Once
      features have been found at autopsy to indicate that the deceased may have come
      from a traditional aboriginal background, one can check for particular conditions
      with a high prevalence in tribal communities. Additionally, standard reporting
      practices may be modified to assist in traditional practices and rituals. The
      identification of a skeleton as aboriginal often means that the burial was
      historical and that a concealed homicide with body disposal is unlikely. Steps
      can then be taken to ensure that the remains are returned to aboriginal
      people/traditional landowners who will be able to re-inter the bones in a manner
      that is culturally sensitive and appropriate to their needs and belief systems. 

PMID- 25870050
TI  - Total anomalous pulmonary venous connection : Autopsy considerations.
AB  - Total anomalous pulmonary venous connection (TAPVC), where the pulmonary venous
      circulation drains into the systemic venous circulation rather than into the left
      atrium, may present a number of problems at autopsy. A 5-week-old infant is
      reported who died suddenly and unexpectedly who was found at autopsy to have
      infradiaphragmatic TAPVC into the portal vein. The only associated anomalies were
      a tri-lobed left lung, a patent ductus arteriosus, and drainage of the inferior
      vena cava into the both the right and left atria. This case demonstrates
      particular features that may lead to difficulties in establishing the diagnosis
      of TAPVC. Sudden death in the absence of symptoms in this age group raises the
      possibilities of sudden infant death syndrome (SIDS) and inflicted injury, both
      of which were discounted in this case. An autopsy approach is outlined to
      maximize chances of diagnosing this entity that includes meticulous inspection
      and dissection of cardiac vascular connections before evisceration, with
      photographic documentation of findings. Concurrent cardiovascular abnormalities,
      including valve atresias, septal defects, and left heart hypoplasia are likely in
      the presence of asplenia/polysplenia syndrome. Extracardiac anomalies may be
      present in the form of Holt-Oram, Ellis-van Creveld, and cat eye syndromes.
      Careful examination of the common draining vein for obstructive features is an
      important part of the postmortem assessment. The possibility of heritable cases
      requires referral of the family for genetic evaluation. 

PMID- 25870051
TI  - Lab-on-a-chip technology.
AB  - The techniques and laboratory processes involved in the production of DNA
      profiles for forensic applications are well developed, robust, and reliable.
      Unfortunately, they can now also be considered too slow and expensive to be able
      to match the ever-increasing demands placed upon them. The most rapid DNA
      profiling instrumentation in current usage are capillary electrophoresis (CE)
      systems. CE systems have greatly enhanced visualization and analysis throughput,
      but are still unable to keep up with current demand. However, developments in
      nanobiotechnology are allowing for the production of miniature systems to
      decrease the time and costs involved in profile production. 

PMID- 25870054
TI  - PME-1-producing Pseudomonas aeruginosa in Qatar.

PMID- 25870053
TI  - Pharmacokinetic determinants of virological response to raltegravir in the in
      vitro pharmacodynamic hollow-fiber infection model system.
AB  - Daily administration (q24h) of raltegravir has been shown to be as efficacious as
      twice-daily administration (q12h) in the hollow-fiber infection model (HFIM)
      system. However, q24h regimens were not noninferior to q12h dosing in a clinical
      trial. We hypothesized that between-patient variability in raltegravir
      pharmacokinetics (PK) was responsible for the discordance in conclusions between
      the in vitro and in vivo studies. Hollow-fiber cartridges were inoculated with
      HIV-infected H9 cells and uninfected CEM-SS cells. Four cartridges received the
      total daily exposure (800 mg) q24h and four received half the daily exposure (400
      mg) q12h. PK profiles with half-lives of 8, 4, 3, and 2 h were simulated for each
      dosing interval. Cell-to-cell viral spread was assessed by flow cytometry. Viral
      inhibition was similar between q24h and q12h dosing at the 8- and 4-h half-lives.
      The q24h dosing was not as efficacious as the q12h dosing when faster half-lives
      were simulated; a lack of viral suppression was observed at days 3 and 4 for the
      2- and 3-h half-lives, respectively. The discrepancy in conclusions between the
      in vitro HFIM system studies and clinical trials is likely due to the large
      interindividual variation in raltegravir PK.

PMID- 25870055
TI  - Bactericidal activities of cathelicidin LL-37 and select cationic lipids against
      the hypervirulent Pseudomonas aeruginosa strain LESB58.
AB  - Pseudomonas aeruginosa Liverpool epidemic strain (LES) infections in cystic
      fibrosis (CF) patients are associated with transmissibility and increased patient
      morbidity. This study was designed to assess the in vitro activities of
      cathelicidin LL-37 peptide (LL-37) and select cationic lipids against Pseudomonas
      aeruginosa LESB58 in CF sputum and in a setting mimicking the CF airway. We found
      that LL-37 naturally present in airway surface fluid and some nonpeptide cationic
      lipid molecules such as CSA-13, CSA-90, CSA-131, and D2S have significant, but
      broadly differing, bactericidal activities against P. aeruginosa LESB58. We
      observed strong inhibition of LL-37 bactericidal activity in the presence of
      purified bacteriophage Pf1, which is highly expressed by P. aeruginosa LES, but
      the activities of the cationic lipids CSA-13 and CSA-131 were not affected by
      this polyanionic virus. Additionally, CSA-13 and CSA-131 effectively prevent
      LESB58 biofilm formation, which is stimulated by Pf1 bacteriophage, DNA, or F
      actin. CSA-13 and CSA-131 display strong antibacterial activities against
      different clinical strains of P. aeruginosa, and their activities against P.
      aeruginosa LESB58 and Xen5 strains were maintained in CF sputum. These data
      indicate that synthetic cationic lipids (mimics of natural antimicrobial
      peptides) are suitable for developing an effective treatment against CF lung P.
      aeruginosa infections, including those caused by LES strains.

PMID- 25870056
TI  - Safety and Pharmacokinetics of Solithromycin in Subjects with Hepatic Impairment.
AB  - Solithromycin, a new macrolide and the first fluoroketolide, is in late-stage
      clinical development and, like older macrolides, is primarily metabolized and
      excreted through liver-dependent mechanisms. This study evaluated the safety and
      pharmacokinetics of solithromycin in patients with chronic liver disease. This
      open-label, multiple-dose study in subjects with hepatic impairment and in
      healthy control subjects (matched for age, weight, and sex) enrolled 8 Child-Pugh
      class A (mild), 8 class B (moderate), and 8 class C (severe) patients and 9
      healthy controls. Subjects (n = 33) received one 800-mg dose on day 1 followed by
      once-daily doses of 400 mg on days 2 through 5. The most commonly reported
      adverse events were mild diarrhea and mild headache, and no significant
      differences were noted between hepatically impaired subjects and healthy
      controls. The pharmacokinetics of plasma solithromycin in subjects with mild and
      moderate impairment was similar to that in control subjects. In subjects with
      severe impairment, total exposure to solithromycin at steady state (area under
      the plasma concentration-time curve [AUC0-tau]) was decreased compared to that in
      control subjects, which may have been related to the higher body mass index of
      individuals in this group. No greater accumulation was noted in any hepatically
      impaired cohort on day 5 compared to that in control subjects. No decrease in
      dosage is therefore needed when administering solithromycin to patients with
      mild, moderate, or severe hepatic impairment. Solithromycin was well tolerated in
      this patient population, and no significant differences in safety, compared to
      healthy controls, were noted. 

PMID- 25870057
TI  - Pharmacokinetic interactions between BMS-626529, the active moiety of the HIV-1
      attachment inhibitor prodrug BMS-663068, and ritonavir or ritonavir-boosted
      atazanavir in healthy subjects.
AB  - BMS-663068 is a prodrug of BMS-626529, a first-in-class attachment inhibitor that
      binds directly to HIV-1 gp120, preventing initial viral attachment and entry into
      host CD4(+) T cells. This open-label, multiple-dose, four-sequence, crossover
      study addressed potential two-way drug-drug interactions following
      coadministration of BMS-663068 (BMS-626529 is a CYP3A4 substrate), atazanavir
      (ATV), and ritonavir (RTV) (ATV and RTV are CYP3A4 inhibitors). Thirty-six
      healthy subjects were randomized 1:1:1:1 to receive one of four treatment
      sequences with three consecutive treatments: BMS-663068 at 600 mg twice daily
      (BID), BMS-663068 at 600 mg BID plus RTV at 100 mg once daily (QD), ATV at 300 mg
      QD plus RTV at 100 mg QD (RTV-boosted ATV [ATV/r]), or BMS-663068 at 600 mg BID
      plus ATV at 300 mg QD plus RTV at 100 mg QD. Compared with the results obtained
      by administration of BMS-663068 alone, coadministration of BMS-663068 with ATV/r
      increased the BMS-626529 maximum concentration in plasma (Cmax) and the area
      under the concentration-time curve in one dosing interval (AUCtau) by 68% and
      54%, respectively. Similarly, coadministration of BMS-663068 with RTV increased
      the BMS-626529 Cmax and AUCtau by 53% and 45%, respectively. Compared with the
      results obtained by administration of ATV/r alone, ATV and RTV systemic exposures
      remained similar following coadministration of BMS-663068 with ATV/r. BMS-663068
      was generally well tolerated, and there were no adverse events (AEs) leading to
      discontinuation, serious AEs, or deaths. Moderate increases in BMS-626529
      systemic exposure were observed following coadministration of BMS-663068 with
      ATV/r or RTV. However, the addition of ATV to BMS-663068 plus RTV did not further
      increase BMS-626529 systemic exposure. ATV and RTV exposures remained similar
      following coadministration of BMS-663068 with either ATV/r or RTV. BMS-663068 was
      generally well tolerated alone or in combination with either RTV or ATV/r.

PMID- 25870058
TI  - War wound treatment complications due to transfer of an IncN plasmid harboring
      bla(OXA-181) from Morganella morganii to CTX-M-27-producing sequence type 131
      Escherichia coli.
AB  - A 22-year-old male developed a recurrent sacral abscess associated with embedded
      shrapnel following a blast injury. Cultures grew extended-spectrum beta-lactamase
      (ESBL)-producing, carbapenem-susceptible Escherichia coli. Ertapenem was
      administered, but the infection recurred after each course of antibiotics.
      Initial surgical interventions were unsuccessful, and subsequent cultures yielded
      E. coli and Morganella morganii, both nonsusceptible to carbapenems. The isolates
      were Carba NP test negative, gave ambiguous results with the modified Hodge test,
      and amplified the bla(OXA48)-like gene by real-time PCR. All E. coli isolates
      were sequence type 131 (ST131), carried nine resistance genes (including bla(CTX
      M-27)) on an IncF plasmid, and were identical by genome sequencing, except for
      150 kb of plasmid DNA in carbapenem-nonsusceptible isolates only. Sixty kilobases
      of this was shared by M. morganii and represented an IncN plasmid harboring
      bla(OXA-181). In M. morganii, the gene was flanked by IS3000 and ISKpn19, but in
      all but one of the E. coli isolates containing bla(OXA-181), a second copy of
      ISKpn19 had inserted adjacent to IS3000. To the best of our knowledge, this is
      the first report of bla(OXA-181) in the virulent ST131 clonal group and carried
      by the promiscuous IncN family of plasmids. The tendency of M. morganii to have
      high MICs of imipenem, a bla(OXA-181) substrate profile that includes penicillins
      but not extended-spectrum cephalosporins, and weak carbapenemase activity almost
      resulted in the presence of bla(OXA-181) being overlooked. We highlight the
      importance of surveillance for carbapenem resistance in all species, even those
      with intrinsic resistances, and the value of advanced molecular techniques in
      detecting subtle genetic changes.

PMID- 25870059
TI  - Implications of efficient hepatic delivery by tenofovir alafenamide (GS-7340) for
      hepatitis B virus therapy.
AB  - Tenofovir alafenamide (TAF) is a prodrug of tenofovir (TFV) currently in clinical
      evaluation for treatment for HIV and hepatitis B virus (HBV) infections. Since
      the target tissue for HBV is the liver, the hepatic delivery and metabolism of
      TAF in primary human hepatocytes in vitro and in dogs in vivo were evaluated
      here. Incubation of primary human hepatocytes with TAF resulted in high levels of
      the pharmacologically active metabolite tenofovir diphosphate (TFV-DP), which
      persisted in the cell with a half-life of >24 h. In addition to passive
      permeability, studies of transfected cell lines suggest that the hepatic uptake
      of TAF is also facilitated by the organic anion-transporting polypeptides 1B1 and
      1B3 (OATP1B1 and OATP1B3, respectively). In order to inhibit HBV reverse
      transcriptase, TAF must be converted to the pharmacologically active form, TFV
      DP. While cathepsin A is known to be the major enzyme hydrolyzing TAF in cells
      targeted by HIV, including lymphocytes and macrophages, TAF was primarily
      hydrolyzed by carboxylesterase 1 (CES1) in primary human hepatocytes, with
      cathepsin A making a small contribution. Following oral administration of TAF to
      dogs for 7 days, TAF was rapidly absorbed. The appearance of the major metabolite
      TFV in plasma was accompanied by a rapid decline in circulating TAF. Consistent
      with the in vitro data, high and persistent levels of TFV-DP were observed in dog
      livers. Notably, higher liver TFV-DP levels were observed after administration of
      TAF than those given TDF. These results support the clinical testing of once
      daily low-dose TAF for the treatment of HBV infection.

PMID- 25870060
TI  - Blocking Hsp70 enhances the efficiency of amphotericin B treatment against
      resistant Aspergillus terreus strains.
AB  - The polyene antifungal amphotericin B (AmB) is widely used to treat life
      threatening fungal infections. Even though AmB resistance is exceptionally rare
      in fungi, most Aspergillus terreus isolates exhibit an intrinsic resistance
      against the drug in vivo and in vitro. Heat shock proteins perform a fundamental
      protective role against a multitude of stress responses, thereby maintaining
      protein homeostasis in the organism. In this study, we elucidated the role of
      heat shock protein 70 (Hsp70) family members and compared resistant and
      susceptible A. terreus clinical isolates. The upregulation of cytoplasmic Hsp70
      members at the transcriptional as well as translational levels was significantly
      higher with AmB treatment than without AmB treatment, particularly in resistant
      A. terreus isolates, thereby indicating a role of Hsp70 proteins in the AmB
      response. We found that Hsp70 inhibitors considerably increased the
      susceptibility of resistant A. terreus isolates to AmB but exerted little impact
      on susceptible isolates. Also, in in vivo experiments, using the Galleria
      mellonella infection model, cotreatment of resistant A. terreus strains with AmB
      and the Hsp70 inhibitor pifithrin-MU resulted in significantly improved survival
      compared with that achieved with AmB alone. Our results point to an important
      mechanism of regulation of AmB resistance by Hsp70 family members in A. terreus
      and suggest novel drug targets for the treatment of infections caused by
      resistant fungal isolates.

PMID- 25870061
TI  - Development and validation of a high-throughput cell-based screen to identify
      activators of a bacterial two-component signal transduction system.
AB  - CpxRA is a two-component signal transduction system (2CSTS) found in many drug
      resistant Gram-negative bacteria. In response to periplasmic stress, CpxA
      autophosphorylates and donates a phosphoryl group to its cognate response
      regulator, CpxR. Phosphorylated CpxR (CpxR-P) upregulates genes involved in
      membrane repair and downregulates multiple genes that encode virulence factors,
      which are trafficked across the cell membrane. Mutants that constitutively
      activate CpxRA in Salmonella enterica serovar Typhimurium and Haemophilus ducreyi
      are avirulent in mice and humans, respectively. Thus, the activation of CpxRA has
      high potential as a novel antimicrobial/antivirulence strategy. Using a series of
      Escherichia coli strains containing a CpxR-P-responsive lacZ reporter and
      deletions in genes encoding CpxRA system components, we developed and validated a
      novel cell-based high-throughput screen (HTS) for CpxRA activators. A screen of
      36,000 compounds yielded one hit compound that increased reporter activity in
      wild-type cells. This is the first report of a compound that activates, rather
      than inhibits, a 2CSTS. The activity profile of the compound against CpxRA
      pathway mutants in the presence of glucose suggested that the compound inhibits
      CpxA phosphatase activity. We confirmed that the compound induced the
      accumulation of CpxR-P in treated cells. Although the hit compound contained a
      nitro group, a derivative lacking this group retained activity in serum and had
      lower cytotoxicity than that of the initial hit. This HTS is amenable for the
      screening of larger libraries to find compounds that activate CpxRA by other
      mechanisms, and it could be adapted to find activators of other two-component
      systems.

PMID- 25870062
TI  - Genetic and biochemical characterization of OXA-405, an OXA-48-type extended
      spectrum beta-lactamase without significant carbapenemase activity.
AB  - The epidemiology of carbapenemases worldwide is showing that OXA-48 variants are
      becoming the predominant carbapenemase type in Enterobacteriaceae in many
      countries. However, not all OXA-48 variants possess significant activity toward
      carbapenems (e.g., OXA-163). Two Serratia marcescens isolates with resistance
      either to carbapenems or to extended-spectrum cephalosporins were successively
      recovered from the same patient. A genomic comparison using pulsed-field gel
      electrophoresis and automated Rep-PCR typing identified a 97.8% similarity
      between the two isolates. Both strains were resistant to penicillins and first
      generation cephalosporins. The first isolate was susceptible to expanded-spectrum
      cephalosporins, was resistant to carbapenems, and had a significant carbapenemase
      activity (positive Carba NP test) related to the expression of OXA-48. The second
      isolate was resistant to expanded-spectrum cephalosporins, was susceptible to
      carbapenems, and did not express a significant imipenemase activity, (negative
      for the Carba NP test) despite possessing a blaOXA-48-type gene. Sequencing
      identified a novel OXA-48-type beta-lactamase, OXA-405, with a four-amino-acid
      deletion compared to OXA-48. The blaOXA-405 gene was located on a ca. 46-kb
      plasmid identical to the prototype IncL/M blaOXA-48-carrying plasmid except for a
      ca. 16.4-kb deletion in the tra operon, leading to the suppression of self
      conjugation properties. Biochemical analysis showed that OXA-405 has clavulanic
      acid-inhibited activity toward expanded-spectrum activity without significant
      imipenemase activity. This is the first identification of a successive switch of
      catalytic activity in OXA-48-like beta-lactamases, suggesting their plasticity.
      Therefore, this report suggests that the first-line screening of carbapenemase
      producers in Enterobacteriaceae may be based on the biochemical detection of
      carbapenemase activity in clinical settings.

PMID- 25870063
TI  - MIV-150/zinc acetate gel inhibits cell-associated simian-human immunodeficiency
      virus reverse transcriptase infection in a macaque vaginal explant model.
AB  - The transmission of both cell-free and cell-associated immunodeficiency viruses
      has been demonstrated directly in multiple animal species and possibly occurs in
      humans, as suggested by genotyping of the infecting human immunodeficiency virus
      (HIV) in acutely infected women and in semen from their partners. Therefore, a
      microbicide may need to block both mechanisms of HIV transmission to achieve
      maximum efficacy. To date, most of the preclinical evaluation of candidate
      microbicides has been performed using cell-free HIV. New models of mucosal
      transmission of cell-associated HIV are needed to evaluate candidate microbicide
      performance. The MIV-150/zinc acetate/carrageenan (MZC) gel protects Depo-Provera
      treated macaques against cell-free simian-human immunodeficiency virus reverse
      transcriptase (SHIV-RT) infection when applied vaginally up to 8 h before
      challenge. We recently demonstrated the potent activity of MZC gel against cell
      free SHIV-RT in macaque vaginal explants. In the current study, we established a
      cell-associated SHIV-RT infection model of macaque vaginal tissues and tested the
      activity of MZC gel in this model. MZC gel protected tissues against cell
      associated SHIV-RT infection when present at the time of viral exposure or when
      applied up to 4 days prior to viral challenge. These data support clinical
      testing of the MZC gel. Overall, our ex vivo model of cell-associated SHIV-RT
      infection in macaque vaginal mucosa complements the cell-free infection models,
      providing tools for prioritization of products that block both modes of HIV
      transmission.

PMID- 25870064
TI  - Factors associated with antibiotic misuse in outpatient treatment for upper
      respiratory tract infections.
AB  - The Centers for Disease Control and Prevention has promoted the appropriate use
      of antibiotics since 1995 when it initiated the National Campaign for Appropriate
      Antibiotic Use in the Community. This study examined upper respiratory tract
      infections included in the campaign to determine the degree to which antibiotics
      were appropriately prescribed and subsequent admission rates in a veteran
      population. This study was a retrospective chart review conducted among
      outpatients with a diagnosis of a respiratory tract infection, including
      bronchitis, pharyngitis, sinusitis, or nonspecific upper respiratory tract
      infection, between January 2009 and December 2011. The study found that 595
      (35.8%) patients were treated appropriately, and 1,067 (64.2%) patients received
      therapy considered inappropriate based on the Get Smart Campaign criteria.
      Overall the subsequent readmission rate was 1.5%. The majority (77.5%) of
      patients were prescribed an antibiotic. The most common antibiotics prescribed
      were azithromycin (39.0%), amoxicillin-clavulanate (13.2%), and moxifloxacin
      (7.5%). A multivariate regression analysis demonstrated significant predictors of
      appropriate treatment, including the presence of tonsillar exudates (odds ratio
      [OR], 0.6; confidence interval [CI], 0.3 to 0.9), fever (OR, 0.6; CI, 0.4 to
      0.9), and lymphadenopathy (OR, 0.4; CI, 0.3 to 0.6), while penicillin allergy
      (OR, 2.9; CI, 1.7 to 4.7) and cough (OR, 1.6; CI, 1.1 to 2.2) were significant
      predictors for inappropriate treatment. Poor compliance with the Get Smart
      Campaign was found in outpatients for respiratory infections. Results from this
      study demonstrate the overprescribing of antibiotics, while providing a focused
      view of improper prescribing. This article provides evidence that current efforts
      are insufficient for curtailing inappropriate antibiotic use.

PMID- 25870066
TI  - Dissemination of the same cfr-carrying plasmid among methicillin-resistant
      Staphylococcus aureus and coagulase-negative staphylococcal isolates in China.
AB  - Six cfr-harboring methicillin-resistant Staphylococcus aureus (MRSA) isolates,
      which belonged to the same clone of sequence type 5 (ST5)-staphylococcal cassette
      chromosome mec element II (SCCmec II)-spa t311, were investigated in this study.
      Complete sequencing of a cfr-carrying plasmid, pLRSA417, revealed an 8,487-bp
      fragment containing a Tn4001-like transposon, cfr, orf1, and ISEnfa4. This
      segment, first identified in an animal plasmid, pSS-01, was observed in several
      plasmids from clinical coagulase-negative staphylococci in China, suggesting that
      the cfr gene, which might originate from livestock, was located in the same
      mobile element and disseminated among different clinical staphylococcal species.

PMID- 25870065
TI  - Contribution of stress responses to antibiotic tolerance in Pseudomonas
      aeruginosa biofilms.
AB  - Enhanced tolerance of biofilm-associated bacteria to antibiotic treatments is
      likely due to a combination of factors, including changes in cell physiology as
      bacteria adapt to biofilm growth and the inherent physiological heterogeneity of
      biofilm bacteria. In this study, a transcriptomics approach was used to identify
      genes differentially expressed during biofilm growth of Pseudomonas aeruginosa.
      These genes were tested for statistically significant overlap, with independently
      compiled gene lists corresponding to stress responses and other putative
      antibiotic-protective mechanisms. Among the gene groups tested were those
      associated with biofilm response to tobramycin or ciprofloxacin, drug efflux
      pumps, acyl homoserine lactone quorum sensing, osmotic shock, heat shock, hypoxia
      stress, and stationary-phase growth. Regulons associated with Anr-mediated
      hypoxia stress, RpoS-regulated stationary-phase growth, and osmotic stress were
      significantly enriched in the set of genes induced in the biofilm. Mutant strains
      deficient in rpoS, relA and spoT, or anr were cultured in biofilms and challenged
      with ciprofloxacin and tobramycin. When challenged with ciprofloxacin, the mutant
      strain biofilms had 2.4- to 2.9-log reductions in viable cells compared to a 0.9
      log reduction of the wild-type strain. Interestingly, none of the mutants
      exhibited a statistically significant alteration in tobramycin susceptibility
      compared to that with the wild-type biofilm. These results are consistent with a
      model in which multiple genes controlled by overlapping starvation or stress
      responses contribute to the protection of a P. aeruginosa biofilm from
      ciprofloxacin. A distinct and as yet undiscovered mechanism protects the biofilm
      bacteria from tobramycin.

PMID- 25870067
TI  - Antimalarial activity of tulathromycin in a murine model of malaria.
AB  - There is an urgent need for new antimalarial agents and strategies to treat and
      control malaria. This study shows an antiplasmodium effect of tulathromycin in
      mice infected with Plasmodium yoelii. The administration of tulathromycin around
      the time of infection prevented the progression of disease in 100% of the
      animals. In addition, highly parasitized mice treated with tulathromycin showed a
      decreased parasite burden and cleared the parasite faster than did untreated
      infected mice.

PMID- 25870068
TI  - Limited sampling strategy and target attainment analysis for levofloxacin in
      patients with tuberculosis.
AB  - There is an urgent need to improve and shorten the treatment of tuberculosis (TB)
      and multidrug resistant tuberculosis (MDR-TB). Levofloxacin, a newer
      fluoroquinolone, has potent activity against TB both in vitro and in vivo.
      Levofloxacin dosing can be optimized to improve the treatment of both TB and MDR
      TB. Levofloxacin efficacy is linked primarily to the ratio of the area under the
      concentration-time curve for the free fraction of drug (fAUC) to the MIC. Since
      obtaining a full-time concentration profile is not feasible in the clinic, we
      developed a limited sampling strategy (LSS) to estimate the AUC. We also utilized
      Monte Carlo simulations to evaluate the dosing of levofloxacin. Pharmacokinetic
      data were obtained from 10 Brazilian TB patients. The pharmacokinetic data were
      fitted with a one-compartment model. LSSs were developed using two methods:
      linear regression and Bayesian approaches. Several LSSs predicted levofloxacin
      AUC with good accuracy and precision. The most accurate were the method using two
      samples collected at 4 and 6 h (R(2) = 0.91 using linear regression and 0.97
      using Bayesian approaches) and that using samples collected at 2 and 6 h (R(2) =
      0.90 using linear regression and 0.96 using Bayesian approaches). The 2-and-6-h
      approach also provides a good estimate of the maximum concentration of the drug
      in serum (Cmax). Our target attainment analysis showed that higher doses (17 to
      20 mg/kg of body weight) of levofloxacin might be needed to improve its activity.
      Doses in the range of 17 to 20 mg/kg showed good target attainment for MICs from
      0.25 to 0.50. At an MIC of 2, poor target attainment was observed across all
      doses. This LSS for levofloxacin can be used for therapeutic drug monitoring and
      for future pharmacokinetic/pharmacodynamic studies.

PMID- 25870070
TI  - Molecular characterization of ISCR1-mediated blaPER-1 in a non-O1, non-O139
      Vibrio cholerae strain from China.
AB  - We report the detection of PER-1 extended-spectrum beta-lactamase (ESBL) in a
      clinical non-O1, non-O139 Vibrio cholerae strain from China. ISCR1-mediated
      bla(PER-1) was embedded in a complex In4 family class 1 integron belonging to the
      lineage of Tn1696 on a conjugative IncA/C plasmid. A free 8.98-kb circular
      molecule present with the ISCR1-bla(PER-1)-truncated 3'-conserved sequence (CS)
      structure was detected in this isolate. These findings may provide insight into
      the mobilization of bla(PER-1).

PMID- 25870069
TI  - Differential cytochrome P450 2D metabolism alters tafenoquine pharmacokinetics.
AB  - Cytochrome P450 (CYP) 2D metabolism is required for the liver-stage antimalarial
      efficacy of the 8-aminoquinoline molecule tafenoquine in mice. This could be
      problematic for Plasmodium vivax radical cure, as the human CYP 2D ortholog (2D6)
      is highly polymorphic. Diminished CYP 2D6 enzyme activity, as in the poor
      metabolizer phenotype, could compromise radical curative efficacy in humans.
      Despite the importance of CYP 2D metabolism for tafenoquine liver-stage efficacy,
      the exact role that CYP 2D metabolism plays in the metabolism and
      pharmacokinetics of tafenoquine and other 8-aminoquinoline molecules has not been
      extensively studied. In this study, a series of tafenoquine pharmacokinetic
      experiments were conducted in mice with different CYP 2D metabolism statuses,
      including wild-type (WT) (reflecting extensive metabolizers for CYP 2D6
      substrates) and CYPmouse 2D knockout (KO) (reflecting poor metabolizers for CYP
      2D6 substrates) mice. Plasma and liver pharmacokinetic profiles from a single 20
      mg/kg of body weight dose of tafenoquine differed between the strains; however,
      the differences were less striking than previous results obtained for primaquine
      in the same model. Additionally, the presence of a 5,6-ortho-quinone tafenoquine
      metabolite was examined in both mouse strains. The 5,6-ortho-quinone species of
      tafenoquine was observed, and concentrations of the metabolite were highest in
      the WT extensive-metabolizer phenotype. Altogether, this study indicates that CYP
      2D metabolism in mice affects tafenoquine pharmacokinetics and could have
      implications for human tafenoquine pharmacokinetics in polymorphic CYP 2D6 human
      populations.

PMID- 25870071
TI  - Evaluation of a modified EUCAST fragmented-mycelium inoculum method for in vitro
      susceptibility testing of dermatophytes and the activity of novel antifungal
      agents.
AB  - For antifungal susceptibility testing of nonsporulating or poorly sporulating
      dermatophytes, a fragmented-mycelium inoculum preparation method was established
      and compared to broth microdilution testing according to CLSI and EUCAST
      guidelines. Moreover, the in vitro activity of new antifungal agents against
      dermatophytes was evaluated. Agreement between the mycelial inoculum method and
      the CLSI broth microdilution method was high (93% to 100%). Echinocandins
      (minimal effective concentration [MEC], <=0.5 mg/liter) and posaconazole (MIC,
      <=3.00 mg/liter) showed good activity against all tested dermatophytes.

PMID- 25870072
TI  - In vivo cluster formation of nisin and lipid II is correlated with membrane
      depolarization.
AB  - Nisin and related lantibiotics kill bacteria by pore formation or by sequestering
      lipid II. Some lantibiotics sequester lipid II into clusters, which were
      suggested to kill cells through delocalized peptidoglycan synthesis. Here, we
      show that cluster formation is always concomitant with (i) membrane pore
      formation and (ii) membrane depolarization. Nisin variants that cluster lipid II
      kill L-form bacteria with similar efficiency, suggesting that delocalization of
      peptidoglycan synthesis is not the primary killing mechanism of these
      lantibiotics.

PMID- 25870073
TI  - Narrow-spectrum inhibitors of Campylobacter jejuni flagellar expression and
      growth.
AB  - Campylobacter jejuni is a major cause of food-borne illness due to its ability to
      reside within the gastrointestinal tracts of chickens. Multiple studies have
      identified the flagella of C. jejuni as a major determinant of chicken
      colonization. An inhibitor screen of approximately 147,000 small molecules was
      performed to identify compounds that are able to inhibit flagellar expression in
      a reporter strain of C. jejuni. Several compounds that modestly inhibited
      motility of wild-type C. jejuni in standard assays were identified, as were a
      number of small molecules that robustly inhibited C. jejuni growth, in vitro.
      Examination of similar bacterial screens found that many of these small molecules
      inhibited only the growth of C. jejuni. Follow-up assays demonstrated inhibition
      of other strains of C. jejuni and Campylobacter coli but no inhibition of the
      closely related Helicobacter pylori. The compounds were determined to be
      bacteriostatic and nontoxic to eukaryotic cells. Preliminary results from a day
      of-hatch chick model of colonization suggest that at least one of the compounds
      demonstrates promise for reducing Campylobacter colonization loads in vivo,
      although further medicinal chemistry may be required to enhance bioavailability.

PMID- 25870074
TI  - Inhibition of human cytomegalovirus replication by artemisinins: effects mediated
      through cell cycle modulation.
AB  - Artemisinin-derived monomers and dimers inhibit human cytomegalovirus (CMV)
      replication in human foreskin fibroblasts (HFFs). The monomer artesunate (AS)
      inhibits CMV at micromolar concentrations, while dimers inhibit CMV replication
      at nanomolar concentrations, without increased toxicity in HFFs. We report on the
      variable anti-CMV activity of AS compared to the consistent and reproducible CMV
      inhibition by dimer 606 and ganciclovir (GCV). Investigation of this phenomenon
      revealed that the anti-CMV activity of AS correlated with HFFs synchronized to
      the G0/G1 stage of the cell cycle. In contact-inhibited serum-starved HFFs or
      cells arrested at early/late G1 with specific checkpoint regulators, AS and dimer
      606 efficiently inhibited CMV replication. However, in cycling HFFs, in which CMV
      replication was productive, virus inhibition by AS was significantly reduced, but
      inhibition by dimer 606 and GCV was maintained. Cell cycle analysis in
      noninfected HFFs revealed that AS induced early G1 arrest, while dimer 606
      partially blocked cell cycle progression. In infected HFFs, AS and dimer 606
      prevented the progression of cell cycle toward the G1/S checkpoint. AS reduced
      the expression of cyclin-dependent kinases (CDK) 2, 4, and 6 in noninfected
      cycling HFFs, while the effect of dimer 606 on these CDKs was moderate. Neither
      compound affected CDK expression in noninfected contact-inhibited HFFs. In CMV
      infected cells, AS activity correlated with reduced CDK2 levels. CMV inhibition
      by AS and dimer 606 also correlated with hypophosphorylation (activity) of the
      retinoblastoma protein (pRb). AS activity was strongly associated with pRb
      hypophosphorylation, while its reduced anti-CMV activity was marked by pRb
      phosphorylation. Roscovitine, a CDK2 inhibitor, antagonized the anti-CMV
      activities of AS and dimer 606. These data suggest that cell cycle modulation
      through CDKs and pRb might play a role in the anti-CMV activities of
      artemisinins. Proteins involved in this modulation may be identified and targeted
      for CMV inhibition.

PMID- 25870075
TI  - MAPK1 of Leishmania donovani modulates antimony susceptibility by downregulating
      P-glycoprotein efflux pumps.
AB  - Emergence of resistance to pentavalent antimonials has become a severe obstacle
      in the treatment of visceral leishmaniasis (VL) in the Indian subcontinent.
      Mitogen-activated protein kinases (MAPKs) are well-known mediators of signal
      transduction of eukaryotes, regulating important processes, like proliferation,
      differentiation, stress response, and apoptosis. In Leishmania, MAPK1 has been
      shown to be consistently downregulated in antimony-resistant field isolates,
      suggesting that it has a role in antimony resistance. The present work
      investigates the molecular mechanism of MAPK1 in antimony resistance in
      Leishmania donovani. The L. donovani MAPK1 (LdMAPK1) single-allele replacement
      mutants exhibited increased resistance to Sb(III) (5.57-fold) compared to wild
      type promastigotes, while overexpressing parasites became much more susceptible
      to antimony. The LdMAPK1-mediated drug sensitivity was directly related to
      antimony-induced apoptotic death of the parasite, as was evidenced by a 4- to 5
      fold decrease in cell death parameters in deletion mutants and a 2- to 3-fold
      increase in MAPK1-overexpressing cells. LdMAPK1-underexpressing parasites also
      exhibited increased P-glycoprotein (P-gp)-mediated efflux pump activity, while a
      significant decrease in pump activity was observed in overexpressing cells. This
      change in efflux pump activity was directly related to expression levels of P-gp
      in all cell lines. However, episomal complementation of the gene restored normal
      growth, drug sensitivity, P-gp expression, and efflux pump activity. The data
      indicate that LdMAPK1 negatively regulates the expression of P-glycoprotein-type
      efflux pumps in the parasite. The decrease in efflux pump activity with an
      increase in LdMAPK1 expression may result in increased antimony accumulation in
      the parasite, making it more vulnerable to the drug.

PMID- 25870076
TI  - Smartphone apps for spinal surgery: is technology good or evil?
AB  - PURPOSE: The increased utilization of smartphones together with their
      downloadable applications (apps) provides opportunity for doctors, including
      spinal surgeons, to integrate such technology into clinical practice. However,
      the clinical reliability of the medical app sector remains questionable. We
      reviewed available apps themed specifically towards spinal surgery and related
      conditions and assessed the level of medical professional involvement in their
      design and content. METHOD: The most popular smartphone app stores (Android,
      Apple, Blackberry, Windows, Samsung, Nokia) were searched for spinal surgery
      themed apps, using the disease terms Spinal Surgery, Back Surgery, Spine, Disc
      Prolapse, Sciatica, Radiculopathy, Spinal Stenosis, Scoliosis, Spinal Fracture
      and Spondylolisthesis. RESULTS: A total of 78 individual spinal surgery themed
      apps were identified, of which there were six duplicates (N = 72). According to
      app store classifications, there were 57 (79 %) medical themed apps, 11 (15 %)
      health and fitness themed apps, 1 (1 %) business and 3 (4 %) education themed
      apps. Forty-five (63 %) apps were available for download free of charge. For
      those that charged access, the prices ranged from L0.62 to L47.99. Only 44 % of
      spinal surgery apps had customer satisfaction ratings and 56 % had named medical
      professional involvement in their development or content. CONCLUSIONS: This is
      the first study to specifically address the characteristics of apps related to
      spinal surgery. We found that nearly half of spinal surgery apps had no named
      medical professional involvement, raising concerns over app content and evidence
      base for their use. We recommend increased regulation of spinal surgical apps to
      improve the accountability of app content.

PMID- 25870077
TI  - Clinical outcomes and sagittal alignment of single-level unilateral instrumented
      transforaminal lumbar interbody fusion with a 4 to 5-year follow-up.
AB  - PURPOSE: A retrospective study was designed to evaluate clinical outcomes and
      sagittal alignment following single-level unilateral instrumented transforaminal
      lumbar interbody fusion (TLIF). METHODS: From November 2008 to December 2010, a
      total of 139 patients, who suffered from single-level lumbar degenerative
      disease, were included in this study. Forty-seven males and seventy-two females
      with a mean age of 57.3 years were enrolled. The average follow-up period was
      51.7 months with a range of 41-66 months. The follow-up rate was 85.6 %. Thirty
      one patients had diagnosis of discogenic low back pain, ten had recurrent disk
      herniation, thirty-four had spinal stenosis, and fourty-four had
      spondylolisthesis. Clinical outcomes were evaluated using the Oswestry disability
      index (ODI), visual analog scale (VAS) and Japanese Orthopedic Association.
      Operating time, blood loss, length of stay, and complications were also
      evaluated. The sagittal alignment and fusion status were assessed by X-ray and
      three-dimensional computed tomography. RESULTS: The average operating time was
      92.1 +/- 27.5 min, the average blood loss was 135.1 +/- 113.5 ml, and the average
      length of stay was 12.0 +/- 2.9 days. The overall complication rate was 13.4 %,
      and the fusion rate was 82.4 %. The postoperative clinical outcomes and sagittal
      alignment were significantly different from the preoperative values. The final
      lumbar lordosis angle and segment lordosis angle were associated with back pain
      VAS and ODI scores, respectively. CONCLUSION: Unilateral instrumented TLIF is a
      safe and effective treatment option for single-level lumbar degenerative disease,
      and is less invasive, yields good outcomes and has a low complication rate. In
      addition, the procedure has the potential to partly restore sagittal alignment.

PMID- 25870078
TI  - Prospective registry of severe polytrauma. Analysis of 1200 patients.
AB  - INTRODUCTION: Polytrauma continues to be one of the main causes of death in the
      population between 10-40 years of age, and causes severe discapability in
      surviving patients. The aim of this study is to perform an analysis of the
      quality of care of the polytrauma patient using an epidemiological study. METHOD:
      Prospective registry of all polytrauma patients treated at our hospital over 16
      years of age, admitted to the critical care area or dead before admission.
      RESULTS: From March 2006 to August 2014, we registered 1200 polytrauma patients.
      The majority were men (75%) with a median age of 45. The mean ISS was 20,9+/-15,8
      and the most common mechanism of injury was blunt trauma (94% cases), The global
      mortality rate was 9.8% (117 cases), and neurological death was the most frequent
      cause (45.3%), followed by hypovolemic shock (29,1%). In 17 cases (14,5% of
      deaths) mortality was considered evitable or potentially evitable, A total of 327
      patients (27.3%) needed emergency surgery and 106 patients (8,8%) needed
      emergency treatment using interventional radiology. 18,5% of patients (222)
      presented an inadverted injury, with a total of 318 inadverted injuries.
      CONCLUSION: Trauma care at our centre is adequate. A prospective registry of the
      global care of polytrauma patients is necessary to evaluate the quality of care
      and improve results.

PMID- 25870079
TI  - Predictors of Functional and Anatomic Outcomes in Patients with Diabetic Macular
      Edema Treated with Ranibizumab.
AB  - OBJECTIVE: To investigate baseline predictors of month 24 best-corrected visual
      acuity (BCVA) and central foveal thickness (CFT) in patients with diabetic
      macular edema (DME) treated monthly with ranibizumab or sham. DESIGN: Post hoc
      analysis of DME patients in 2 identical phase 3 studies. PARTICIPANTS: Patients
      randomized to ranibizumab (n = 502) or sham (n = 257). METHODS: Multivariate
      regression on predictors with P < 0.20 in univariate logistic regression using
      backward selection to retain predictors with P < 0.05. MAIN OUTCOME MEASURES:
      Patient characteristics correlating with month 24 BCVA in Early Treatment
      Diabetic Retinopathy Study letter score >=70 (20/40) or <=50 (20/100), gain or
      loss from baseline BCVA of >=15, or CFT <=250 MUm. RESULTS: Baseline predictors
      of BCVA >=20/40 in ranibizumab-treated patients were good BCVA, submacular fluid,
      no cardiovascular disease, no scatter photocoagulation, and male gender, whereas
      in sham-treated patients, they were mild increase in CFT, presence of hard
      exudates in center subfield, and absence of renal disease. Predictors of
      improvement in BCVA letter score >=15 in ranibizumab-treated patients were poor
      BCVA, submacular fluid, young age, and short diabetes duration, and those in sham
      treated patients were poor BCVA, young age, and mild increase in CFT. Predictors
      of resolution of edema (CFT <=250 MUm) in ranibizumab-treated patients were mild
      foveal thickening and prominent subfoveal fluid, and those in sham-treated
      patients were poor BCVA, mild foveal thickening, and statin usage. Month 24 BCVA
      <=20/100 was predicted by poor baseline BCVA in ranibizumab-treated patients, and
      by poor baseline BCVA, large intraretinal cystoid spaces, renal disease, and
      absence of hypercholesterolemia in sham-treated patients. Loss of BCVA >=15
      letters was predicted in sham-treated patients by submacular fluid, intraretinal
      cystoid spaces, and renal disease. CONCLUSIONS: Patients with DME and submacular
      fluid, intraretinal cysts, severe thickening, or renal disease respond poorly
      when untreated and respond well to ranibizumab treatment. Elimination of
      submacular fluid, intraretinal cysts, and severe thickening are important goals
      of DME treatment, and in patients with renal disease, treatment should be very
      aggressive, with a goal of eliminating all macular fluid.

PMID- 25870080
TI  - Charles Bonnet Syndrome in Advanced Retinitis Pigmentosa.

PMID- 25870081
TI  - A Population-Based Ultra-Widefield Digital Image Grading Study for Age-Related
      Macular Degeneration-Like Lesions at the Peripheral Retina.
AB  - PURPOSE: Our understanding of the relevance of peripheral retinal abnormalities
      to disease in general and in age-related macular degeneration (AMD) in particular
      is limited by the lack of detailed peripheral imaging studies. The purpose of
      this study was to develop image grading protocols suited to ultra-widefield
      imaging (UWFI) in an aged population. DESIGN: A cross-sectional study of a random
      population sample in which UWFI was introduced at the 12-year review of the
      Reykjavik Eye Study in Iceland. PARTICIPANTS: Five hundred seventy-six subjects
      62 years of age or older. METHODS: Ultra-widefield (up to 200 degrees ) color and
      autofluorescence images were obtained using the Optos P200CAF laser scanning
      ophthalmoscope (Optos plc, Dunfermline, Scotland). The images were graded at
      Moorfields Eye Hospital Reading Centre primarily based on the International
      Classification for AMD. Macular and peripheral changes were graded using a
      standardized grid developed for this imaging method. MAIN OUTCOME MEASURES:
      Presence or absence of hard, crystalline, and soft drusen; retinal pigment
      epithelial changes; choroidal neovascularization (CNV); atrophy; and
      hypoautofluorescence and hyperautofluorescence were graded in the peripheral
      retina. RESULTS: Of the eyes examined, 81.1% had AMD-like changes in the macula
      alone (13.6%), periphery alone (10.1%), and both periphery and macula (57.4%).
      There was no AMD-like CNV or pigment epithelial detachment in the periphery
      except in those cases in which these clearly originated from the macula. Seven
      patients had AMD-like atrophy in the periphery without end-stage disease in the
      macula. One patient with end-stage disease in the macula had normal periphery
      results on the color images. While analyzing the eyes, we detected pathologic
      appearances that were very reliably identified by graders. CONCLUSIONS:
      Phenotyping the retinal periphery using the categories defined by the
      International Classification confirmed the presence of wide-ranging AMD-like
      pathologic changes even in those without central sight-threatening macular
      disease. Based on our observations, we propose here new, reliably identifiable
      grading categories that may be more suited for population-based UWFI.

PMID- 25870082
TI  - Excitatory amino acid receptors in the dorsomedial hypothalamic area contribute
      to the chemoreflex tachypneic response.
AB  - This study evaluated the effect of blockade of the excitatory amino acid (EAA)
      receptors in the dorsomedial hypothalamic (DMH) area on the ventilatory and
      cardiovascular responses of the chemoreflex activation in conscious rats.
      Bilateral microinjection of kynurenic acid (2.7 nmol, n = 6) into the DMH area
      reduced the tachypneic (+ 264 +/- 13 versus + 204 +/- 14 cpm, P < 0.05) and
      pressor (+ 52 +/- 5 versus + 31 +/- 6 mmHg, P < 0.05) components of chemoreflex
      but had no effect on the bradycardic component (-214 +/- 7 versus -244 +/- 17
      bpm) of the chemoreflex. The magnitudes of the reduction in pressor and
      tachypneic chemoreflex responses were not significantly correlated (r = 0.308, P
      = 0.330). These data indicate that neurons located in the DMH area are activated
      by chemoreflex; that this activation is mediated via EAA receptors; and that it
      is essential for the full expression of the respiratory component of the
      chemoreflex.

PMID- 25870083
TI  - Cardiopulmonary changes with aeration of the newborn lung.
AB  - The newborn's transition from fetal to neonatal life includes aeration of the
      lungs, establishment of pulmonary gas exchange and changing the fetal circulation
      into the adult phenotype. This review summarizes the latest research findings,
      which show that lung aeration, airway liquid clearance and cardiovascular changes
      are directly interconnected at birth. The mechanisms of airway liquid clearance
      at birth are reviewed and the particular importance of the transpulmonary
      pressure gradient during lung aeration is discussed. Further, we summarize
      research findings which prove that lung aeration triggers the increase in
      pulmonary blood flow (PBF) at birth, and how the increase in PBF secures the
      preload for left ventricular output. Consequently, we review animal experiments
      which suggest that delaying umbilical cord clamping until breathing commences
      facilitates hemodynamic stability during transition. These data are reviewed with
      respect to the clinical applicability: As lung aeration is the key to successful
      transition to newborn life, providing adequate respiratory support at birth must
      be the primary objective of neonatal staff attending to the newborn infant.
      Clinical studies are needed to demonstrate whether the obvious benefits of
      delaying cord clamping until breathing commences hold true in human babies. 

PMID- 25870084
TI  - Improvement in binge eating in non-diabetic obese individuals after 3 months of
      treatment with liraglutide - A pilot study.
AB  - We examined the effects of liraglutide, a glucagon-like peptide-1 analogue on
      appetite and plasma ghrelin in non-diabetic obese participants with subclinical
      binge eating (BE). Forty-four obese BE participants (mean age: 34+/-9 years, BMI:
      35.9+/-4.2kg/m(2)) were randomly assigned to intervention or control groups for
      12 weeks. All participants received standard advice for diet and exercise. Binge
      eating score, ghrelin levels and other anthropometric variables were evaluated at
      baseline and at the end of the study. Participants who received liraglutide
      showed significant improvement in binge eating, accompanied by reduction in body
      weight, BMI, waist circumference, systolic blood pressure, fasting glucose and
      total cholesterol. Ghrelin levels were significantly increased which may
      potentially diminish the weight loss effects of liraglutide beyond the
      intervention. 

PMID- 25870085
TI  - Autologous Stem-Cell Transplantation Without Hematopoietic Support for the
      Treatment of Hematologic Malignancies in Jehovah's Witnesses.
AB  - PURPOSE: Autologous stem-cell transplantation (ASCT) has shown to provide
      curative benefit in patients with relapsed lymphoma and multiple myeloma (MM),
      often requiring hematopoietic support until marrow engraftment. Because of
      Jehovah's Witnesses' (JW) refusal of blood products, treatment challenges arise.
      This study represents 125 JWs with lymphoma (n = 55), MM (n = 68), or amyloidosis
      (n = 2), treated with high-dose chemotherapy (HDC) and ASCT without transfusions.
      PATIENTS AND METHODS: Priming with intravenous iron and erythropoietin occurred
      to increase hemoglobin (Hb) pretransplantation. Cytokine mobilization of stem
      cells was used. Delay to HDC was done to allow Hb and platelets to approach 11
      g/dL and 100 * 10(3)/MUL, respectively. Patients with MM received a standard dose
      of melphalan 200 mg/m(2), with dose reduction for severe kidney dysfunction.
      Patients with lymphoma received carmustine 300 mg/m(2), cyclophosphamide 1,500
      mg/m(2) on days 2 through 5 (total 6 g/m(2)), and etoposide 700 mg/m(2) per day
      on days 2 through 4 (total 2,100 mg/m(2)). Post-transplantation, a combination of
      granulocyte colony-stimulating factor, erythropoietin, aminocaproic acid, and
      phytonadione was administered. RESULTS: There were two major and 15 minor
      bleeding complications, none occurring at platelets less than 5.0 * 10(3)/MUL,
      with six (4.8%) treatment-related mortalities. The median decrease in Hb was 5.0
      g/dL, with median Hb nadir of 7.0 g/dL. The median number of days with platelet
      count less than 10 * 10(3)/MUL was 3, with median platelet nadir of 5.0 *
      10(3)/MUL. Cardiac complications occurred in 40 patients (32%). CONCLUSION: ASCT
      can safely be performed without transfusion support. A platelet transfusion
      trigger of <= 5 * 10(3)/MUL may be appropriate in select patients.
      Pharmacotherapy and cardiac monitoring are effective in the management of cardiac
      complications.

PMID- 25870086
TI  - Hope for high-risk chronic lymphocytic leukemia relapsing after allogeneic stem
      cell transplantation.

PMID- 25870088
TI  - Biomarker Analysis in CLEOPATRA: Searching for a Sensitive Prognostic Factor in
      Breast Cancer.

PMID- 25870087
TI  - Phase I/II Study of HSP90 Inhibitor AUY922 and Erlotinib for EGFR-Mutant Lung
      Cancer With Acquired Resistance to Epidermal Growth Factor Receptor Tyrosine
      Kinase Inhibitors.
AB  - PURPOSE: AUY922 is an HSP90 inhibitor that causes degradation of HSP chaperones
      and their client proteins, including epidermal growth factor receptor. We
      conducted a phase I/II trial to evaluate AUY922 and erlotinib for patients with
      EGFR-mutant lung cancer and disease progression during erlotinib treatment.
      PATIENTS AND METHODS: All patients had developed acquired resistance after
      treatment with erlotinib and underwent repeat tumor biopsies before study entry
      to assess for EGFR T790M. In phase I, 18 patients were treated with AUY922
      intravenously once per week and erlotinib once per day in 28-day cycles using a 3
      + 3 dose-escalation design. In phase II, 19 additional patients were treated at
      the maximum-tolerated dose. The primary end point of the phase II trial was
      complete plus partial response rate. RESULTS: In phase I (n = 18), three patients
      were treated in each cohort, except the highest-dose cohort (AUY922 70 mg and
      erlotinib 150 mg), which expanded to six patients because of a dose-limiting
      toxicity (ie, junctional cardiac rhythm). Common drug-related adverse events were
      diarrhea, skin rash, hyperglycemia, and night blindness. All patients treated at
      maximum-tolerated dose (n = 25) were evaluable for response. The partial response
      rate was 16% (four of 25 patients; 95% CI, 5% to 36%) and was independent of
      tumor T790M status. CONCLUSION: Partial responses were observed, but the duration
      of treatment with AUY922 and erlotinib was limited by toxicities, especially
      night blindness. This phase II study of AUY922 and erlotinib did not meet its
      primary end point.

PMID- 25870089
TI  - Sunitinib: the next advance in small-cell lung cancer?

PMID- 25870090
TI  - Reply to F.-C. Bidard et al.

PMID- 25870091
TI  - Clinical utility of circulating tumor cells in metastatic breast cancer.

PMID- 25870092
TI  - Sequencing and combining systemic therapies for pancreatic neuroendocrine tumors.

PMID- 25870093
TI  - Should anticoagulation therapy be withheld in patients with active cancer after 6
      months of low-molecular weight heparin?

PMID- 25870094
TI  - Reply to a. Avan et Al.

PMID- 25870095
TI  - Reply to e.g. Urrego et Al.

PMID- 25870096
TI  - Metrics of quality care in veterans: correlation between primary-care performance
      measures and inappropriate myocardial perfusion imaging.
AB  - BACKGROUND: Approximately 10% to 20% of myocardial perfusion imaging (MPI) tests
      are inappropriate based on professional-society recommendations. The correlation
      between inappropriate MPI and quality care metrics is not known. HYPOTHESIS:
      Inappropriate MPI will be associated with low achievement of quality care
      metrics. METHODS: We conducted a retrospective cross-sectional investigation at a
      single Veterans Affairs medical center. Myocardial perfusion imaging tests
      ordered by primary-care clinicians between December 2010 and July 2011 were
      assessed for appropriateness (by 2009 criteria). Using documentation of the
      clinical encounter where MPI was ordered, we determined how often quality care
      metrics were achieved. RESULTS: Among 516 MPI patients, 52 (10.1%) were
      inappropriate and 464 (89.9%) were not inappropriate (either appropriate or
      uncertain). Hypertension (82.2%), diabetes mellitus (41.3%), and coronary artery
      disease (41.1%) were common. Glycated hemoglobin levels were lower in the
      inappropriate MPI cohort (6.6% vs 7.5%; P = 0.04). No difference was observed in
      the proportion with goal hemoglobin (62.5% vs 46.3% for appropriate/uncertain; P
      = 0.258). Systolic blood pressure was not different (132 mm Hg vs 135 mm Hg; P =
      0.34). Achievement of several other categorical quality metrics was low in both
      cohorts and no differences were observed. More than 90% of clinicians documented
      a plan to achieve most metrics. CONCLUSIONS: Inappropriate MPI is not associated
      with performance on metrics of quality care. If an association exists, it may be
      between inappropriate MPI and overly aggressive care. Most clinicians document a
      plan of care to address failure of quality metrics, suggesting awareness of the
      problem.

PMID- 25870097
TI  - Role of [(18)F]fluorodeoxyglucose positron emission tomography-computed
      tomography for diagnosis and treatment of sarcoidosis in an HIV-2-infected
      patient.

PMID- 25870098
TI  - Vision and eye health: moving into the digital age with instrument-based vision
      screening.
AB  - Significant advancements in vision screening research are leading to improved
      design, functionality, and reliability of screening tools. Presently, two vision
      screening approaches are available to school nurses for children ages 3 years and
      older: optotype-based screening and instrument-based screening. Optotype-based
      screening pertains to tests of visual acuity using optotypes (e.g., pictures,
      letters, and numbers), which children identify to determine visual acuity.
      Instrument-based screening pertains to automated devices that measure amblyogenic
      risk factors, such as refractive error, media opacities, and eye misalignment.
      Differences between the two approaches; best and acceptable practice
      recommendations for both approaches; unacceptable tests of visual acuity; and
      best, acceptable, and unacceptable occluders are described. 

PMID- 25870099
TI  - Correlates of cyberbullying and how school nurses can respond.
AB  - Cyberbullying is one of many online risks that affect an increasing number of
      children and teenagers. This form of abuse often occurs under the radar of adults
      as it usually takes place outside of school and away from adult supervision.
      Moreover, bystanders and victims are often reluctant to report what they have
      experienced. School nurses might be among the first to witness the real-life
      consequences of this virtual behavior, as involvement in cyberbullying is often
      correlated with psychological and behavioral problems. For this reason, school
      nurses should know how to recognize the warning signs so that they can respond
      and intervene appropriately. This article provides a discussion of what
      cyberbullying is and a summary of research on factors associated with
      cyberbullying, in terms of both victimization and perpetration. It also provides
      school nurses with evidence-based strategies for responding effectively. 

PMID- 25870100
TI  - Bullying prevention in schools: position statement.
AB  - It is the position of the National Association of School Nurses that the
      registered professional school nurse (hereinafter referred to as the school
      nurse) is a crucial member of the team participating in the prevention of
      bullying in schools. School nurses are the experts in pediatric health in schools
      and, therefore, can have an impact on the health and safety of all students,
      including students who bully, students who are bullied, or students who both
      bully and are bullied by others (Centers for Disease Control and Prevention
      [CDC], 2011a, 2011b). The school nurse role includes the prevention of bullying
      and the identification of students who are bullied, bully others, or both. The
      school nurse has a significant leadership role in the implementation of bullying
      prevention policies and strategies.

PMID- 25870101
TI  - Glucuronidation of OTS167 in Humans Is Catalyzed by UDP-Glucuronosyltransferases
      UGT1A1, UGT1A3, UGT1A8, and UGT1A10.
AB  - OTS167 is a potent maternal embryonic leucine zipper kinase inhibitor undergoing
      clinical testing as antineoplastic agent. We aimed to identify the UDP
      glucuronosyltransferases (UGTs) involved in OTS167 metabolism, study the
      relationship between UGT genetic polymorphisms and hepatic OTS167
      glucuronidation, and investigate the inhibitory potential of OTS167 on UGTs.
      Formation of a single OTS167-glucuronide (OTS167-G) was observed in pooled human
      liver (HLM) (Km = 3.4 +/- 0.2 uM), intestinal microsomes (HIM) (Km = 1.7 +/- 0.1
      uM), and UGTs. UGT1A1 (64 ul/min/mg) and UGT1A8 (72 ul/min/mg) exhibited the
      highest intrinsic clearances (CLint) for OTS167, followed by UGT1A3 (51
      ul/min/mg) and UGT1A10 (47 ul/min/mg); UGT1A9 was a minor contributor. OTS167
      glucuronidation in HLM was highly correlated with thyroxine glucuronidation (r =
      0.91, P < 0.0001), SN-38 glucuronidation (r = 0.79, P < 0.0001), and UGT1A1 mRNA
      (r = 0.72, P < 0.0001). Nilotinib (UGT1A1 inhibitor) and emodin (UGT1A8 and
      UGT1A10 inhibitor) exhibited the highest inhibitory effects on OTS167-G formation
      in HLM (68%) and HIM (47%). We hypothesize that OTS167-G is an N-glucuronide
      according to mass spectrometry. A significant association was found between
      rs6706232 and reduced OTS167-G formation (P = 0.03). No or weak UGT inhibition
      (range: 0-21%) was observed using clinically relevant OTS167 concentrations (0.4
      2 uM). We conclude that UGT1A1 and UGT1A3 are the main UGTs responsible for
      hepatic formation of OTS167-G. Intestinal UGT1A1, UGT1A8, and UGT1A10 may
      contribute to first-pass OTS167 metabolism after oral administration. 

PMID- 25870102
TI  - Hepatoselective Nitric Oxide (NO) Donors, V-PYRRO/NO and V-PROLI/NO, in
      Nonalcoholic Fatty Liver Disease: A Comparison of Antisteatotic Effects with the
      Biotransformation and Pharmacokinetics.
AB  - V-PYRRO/NO [O(2)-vinyl-1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate] and V
      PROLI/NO (O2-vinyl-[2-(carboxylato)pyrrolidin-1-yl]diazen-1-ium-1,2-diolate), two
      structurally similar diazeniumdiolate derivatives, were designed as liver
      selective prodrugs that are metabolized by cytochrome P450 isoenzymes, with
      subsequent release of nitric oxide (NO). Yet, their efficacy in the treatment of
      nonalcoholic fatty liver disease (NAFLD) and their comparative pharmacokinetic
      and metabolic profiles have not been characterized. The aim of the present work
      was to compare the effects of V-PYRRO/NO and V-PROLI/NO on liver steatosis,
      glucose tolerance, and liver fatty acid composition in C57BL/6J mice fed a high
      fat diet, as well as to comprehensively characterize the ADME (absorption,
      distribution, metabolism and excretion) profiles of both NO donors. Despite their
      similar structure, V-PYRRO/NO and V-PROLI/NO showed differences in
      pharmacological efficacy in the murine model of NAFLD. V-PYRRO/NO, but not V
      PROLI/NO, attenuated liver steatosis, improved glucose tolerance, and favorably
      modified fatty acid composition in the liver. Both compounds were characterized
      by rapid absorption following i.p. administration, rapid elimination from the
      body, and incomplete bioavailability. However, V-PYRRO/NO was eliminated mainly
      by the liver, whereas V-PROLI/NO was excreted mostly in unchanged form by the
      kidney. V-PYRRO/NO was metabolized by CYP2E1, CYP2C9, CYP1A2, and CYP3A4, whereas
      V-PROLI/NO was metabolized mainly by CYP1A2. Importantly, V-PYRRO/NO was a better
      NO releaser in vivo and in the isolated, perfused liver than V-PROLI/NO, an
      effect compatible with the superior antisteatotic activity of V-PYRRO/NO. In
      conclusion, V-PYRRO/NO displayed a pronounced antisteatotic effect associated
      with liver-targeted NO release, whereas V-PROLI/NO showed low effectiveness, was
      not taken up by the liver, and was eliminated mostly in unchanged form by the
      kidney. 

PMID- 25870103
TI  - Carbamazepine-Induced Liver Injury Requires CYP3A-Mediated Metabolism and
      Glutathione Depletion in Rats.
AB  - Carbamazepine (CBZ) is widely used as an antiepileptic agent and causes rare but
      severe liver injury in humans. It has been generally recognized that reactive
      metabolites formed via the metabolic activation reaction contribute to the onset
      of liver injuries by several drugs. However, the role of CBZ metabolism in the
      development of liver injury is not fully understood. In this study, we developed
      a novel rat model of CBZ-induced liver injury and attempted to elucidate the
      associated mechanisms by focusing on the metabolism of CBZ. The repeated
      administration of CBZ for 5 days in combination with l-buthionine sulfoximine
      (BSO), a glutathione (GSH) synthesis inhibitor, resulted in increases in the
      plasma alanine aminotransferase (ALT) levels and centrilobular necrosis in the
      liver that were observed in various degrees. The CBZ and 2-hydroxy-CBZ
      concentrations in the plasma after the last CBZ administration were lower in the
      rats with high plasma ALT levels compared with those with normal plasma ALT
      levels, showing the possibility that the further metabolism of CBZ and/or 2
      hydroxy-CBZ is associated with the liver injury. Although a single administration
      of CBZ did not affect the plasma ALT levels, even when cotreated with BSO,
      pretreatment with dexamethasone, a CYP3A inducer, increased the plasma ALT
      levels. In addition, the rats cotreated with troleandomycin or ketoconazole,
      CYP3A inhibitors, suppressed the increased plasma ALT levels. In conclusion,
      reactive metabolite(s) of CBZ produced by CYP3A under the GSH-depleted condition
      might be involved in the development of liver injury in rats. 

PMID- 25870104
TI  - Competition between Decapping Complex Formation and Ubiquitin-Mediated
      Proteasomal Degradation Controls Human Dcp2 Decapping Activity.
AB  - mRNA decapping is a central step in eukaryotic mRNA decay that simultaneously
      shuts down translation initiation and activates mRNA degradation. A major complex
      responsible for decapping consists of the decapping enzyme Dcp2 in association
      with decapping enhancers. An important question is how the activity and
      accumulation of Dcp2 are regulated at the cellular level to ensure the
      specificity and fidelity of the Dcp2 decapping complex. Here, we show that human
      Dcp2 levels and activity are controlled by a competition between decapping
      complex assembly and Dcp2 degradation. This is mediated by a regulatory domain in
      the Dcp2 C terminus, which, on the one hand, promotes Dcp2 activation via
      decapping complex formation mediated by the decapping enhancer Hedls and, on the
      other hand, targets Dcp2 for ubiquitin-mediated proteasomal degradation in the
      absence of Hedls association. This competition between Dcp2 activation and
      degradation restricts the accumulation and activity of uncomplexed Dcp2, which
      may be important for preventing uncontrolled decapping or for regulating Dcp2
      levels and activity according to cellular needs. 

PMID- 25870105
TI  - Evolutionary emergence of a novel splice variant with an opposite effect on the
      cell cycle.
AB  - Alternative splicing contributes greatly to the diversification of mammalian
      proteomes, but the molecular basis for the evolutionary emergence of splice
      variants remains poorly understood. We have recently found a novel class of
      splicing regulatory elements between the polypyrimidine tract (Py) and 3' AG
      (REPA) at intron ends in many human genes, including the multifunctional PRMT5
      (for protein arginine methyltransferase 5) gene. The PRMT5 element is comprised
      of two G tracts that arise in most mammals and accompany significant exon
      skipping in human transcripts. The G tracts inhibit splicing by recruiting
      heterogeneous nuclear ribonucleoprotein (hnRNP) H and F (H/F) to reduce U2AF65
      binding to the Py, causing exon skipping. The resulting novel shorter variant
      PRMT5S exhibits a histone H4R3 methylation effect similar to that seen with the
      original longer PRMT5L isoform but exhibits a distinct localization and
      preferential control of critical genes for cell cycle arrest at interphase in
      comparison to PRMT5L. This report thus provides a molecular mechanism for the
      evolutionary emergence of a novel splice variant with an opposite function in a
      fundamental cell process. The presence of REPA elements in a large group of genes
      implies their wider impact on different cellular processes for increased protein
      diversity in humans. 

PMID- 25870106
TI  - C1q/Tumor Necrosis Factor-Related Protein 9 Protects against Acute Myocardial
      Injury through an Adiponectin Receptor I-AMPK-Dependent Mechanism.
AB  - Obesity is a risk factor for cardiovascular disease. C1q/tumor necrosis factor
      related protein 9 (CTRP9) is an adipokine that is downregulated by obesity. We
      investigated the role of CTRP9 in cardiac injury with loss-of-function genetic
      manipulations and defined the receptor-mediated signaling pathway downstream of
      this adipokine. CTRP9-knockout (CTRP9-KO) mice at the age of 12 weeks were
      indistinguishable from wild-type (WT) mice under basal conditions. CTRP9-KO mice
      had exacerbated contractile left ventricle dysfunction following intraperitoneal
      injection of lipopolysaccharide (LPS) compared to WT mice. Administration of LPS
      to CTRP9-KO mice also resulted in increased expression of proinflammatory
      cytokines and oxidative stress markers in the heart compared to WT mice.
      Likewise, CTRP9-KO mice showed increased myocardial infarct size and elevated
      expression of inflammatory mediators in ischemic heart following ischemia and
      reperfusion compared to WT mice. Treatment of cardiac myocytes with CTRP9 protein
      led to suppression of LPS-induced expression of proinflammatory genes, which was
      reversed by blockade of AMPK or ablation of adiponectin receptor I (AdipoR1).
      Systemic delivery of CTRP9 attenuated LPS-induced cardiac dysfunction in WT mice
      but not in muscle-specific transgenic mice expressing dominant-negative mutant
      form of AMPK or in AdipoR1-knockout mice. CTRP9 protects against acute cardiac
      damage in response to pathological stimuli by suppressing inflammatory reactions
      through AdipoR1/AMPK-dependent mechanisms. 

PMID- 25870107
TI  - Cleavage of BLOC1S1 mRNA by IRE1 Is Sequence Specific, Temporally Separate from
      XBP1 Splicing, and Dispensable for Cell Viability under Acute Endoplasmic
      Reticulum Stress.
AB  - The unfolded protein response (UPR) remediates endoplasmic reticulum (ER) stress.
      IRE1, a component of the UPR, senses misfolded protein and cleaves XBP1 mRNA,
      which is ligated to code for the prosurvival transcription factor. IRE1 also
      cleaves other mRNAs preceding their degradation, termed regulated IRE1-dependent
      mRNA decay (RIDD). It has been reported that RIDD may be involved in cell
      viability under stress and therefore may contribute to cancer cell viability. To
      investigate RIDD targets that may have functional relevance in cell survival, we
      identified conserved RIDD targets containing stringent IRE1 RNase target
      sequences. Using a systematic bioinformatics approach with quantitative-PCR
      (qPCR) validation, we show that only BLOC1S1 is consistently a RIDD target in all
      systems tested. Using cancer cell lines, we show that BLOC1S1 is specifically
      cleaved by IRE1 at guanine 444, but only under conditions of IRE1
      hyperactivation. BLOC1S1 cleavage is temporally separate from XBP1 splicing,
      occurring after depletion of unspliced XBP1. Expression of an uncleavable BLOC1S1
      mutant or inhibition of RIDD using an IRE1 RNase inhibitor did not affect
      cellular recovery from acute ER stress. These data demonstrate that although
      hyperactivated IRE1 specifically cleaves BLOC1S1, this cleavage event and RIDD as
      a whole are dispensable for cell viability under acute stress. 

PMID- 25870108
TI  - Genetic Analysis of Connective Tissue Growth Factor as an Effector of
      Transforming Growth Factor beta Signaling and Cardiac Remodeling.
AB  - The matricellular secreted protein connective tissue growth factor (CTGF) is
      upregulated in response to cardiac injury or with transforming growth factor beta
      (TGF-beta) stimulation, where it has been suggested to function as a fibrotic
      effector. Here we generated transgenic mice with inducible heart-specific CTGF
      overexpression, mice with heart-specific expression of an activated TGF-beta
      mutant protein, mice with heart-specific deletion of Ctgf, and mice in which Ctgf
      was also deleted from fibroblasts in the heart. Remarkably, neither gain nor loss
      of CTGF in the heart affected cardiac pathology and propensity toward early
      lethality due to TGF-beta overactivation in the heart. Also, neither heart
      specific Ctgf deletion nor CTGF overexpression altered cardiac remodeling and
      function with aging or after multiple acute stress stimuli. Cardiac fibrosis was
      also unchanged by modulation of CTGF levels in the heart with aging, pressure
      overload, agonist infusion, or TGF-beta overexpression. However, CTGF mildly
      altered the overall cardiac response to TGF-beta when pressure overload
      stimulation was applied. CTGF has been proposed to function as a critical TGF
      beta effector in underlying tissue remodeling and fibrosis throughout the body,
      although our results suggest that CTGF is of minimal importance and is an
      unlikely therapeutic vantage point for the heart. 

PMID- 25870109
TI  - TAF10 Interacts with the GATA1 Transcription Factor and Controls Mouse
      Erythropoiesis.
AB  - The ordered assembly of a functional preinitiation complex (PIC), composed of
      general transcription factors (GTFs), is a prerequisite for the transcription of
      protein-coding genes by RNA polymerase II. TFIID, comprised of the TATA binding
      protein (TBP) and 13 TBP-associated factors (TAFs), is the GTF that is thought to
      recognize the promoter sequences allowing site-specific PIC assembly.
      Transcriptional cofactors, such as SAGA, are also necessary for tightly regulated
      transcription initiation. The contribution of the two TAF10-containing complexes
      (TFIID, SAGA) to erythropoiesis remains elusive. By ablating TAF10 specifically
      in erythroid cells in vivo, we observed a differentiation block accompanied by
      deregulated GATA1 target genes, including Gata1 itself, suggesting functional
      cross talk between GATA1 and TAF10. Additionally, we analyzed by mass
      spectrometry the composition of TFIID and SAGA complexes in mouse and human cells
      and found that their global integrity is maintained, with minor changes, during
      erythroid cell differentiation and development. In agreement with our functional
      data, we show that TAF10 interacts directly with GATA1 and that TAF10 is enriched
      on the GATA1 locus in human fetal erythroid cells. Thus, our findings demonstrate
      a cross talk between canonical TFIID and SAGA complexes and cell-specific
      transcription activators during development and differentiation. 

PMID- 25870110
TI  - Novel role for cyclophilin A in regulation of chondrogenic commitment and
      endochondral ossification.
AB  - Recent studies showed that cyclophilin A (CypA) promotes NF-kappaB/p65 nuclear
      translocation, resulting in enhanced NF-kappaB activity and altered expression of
      its target genes, such as the Sox9 transcriptional factor, which plays a critical
      role in chondrogenic differentiation and endochondral ossification. In this
      report, we unveil the role of CypA in signal-induced chondrogenic differentiation
      and endochondral ossification. Expression levels of the chondrogenic
      differentiation markers and transcriptional regulators Sox9 and Runx2 were all
      significantly lower in CypA knockdown chondrogenic cells than in wild-type cells,
      indicating that CypA plays a functional role in chondrogenic differentiation. In
      vitro differentiation studies using micromass cultures of mouse limb bud cells
      further supported the conclusion that CypA is needed for chondrogenic
      differentiation. Newborn CypA-deficient pups double stained with alcian blue and
      alizarin red exhibited generalized, pronounced skeletal defects, while high
      resolution micro-computed tomography (microCT) analyses of the femurs and lumbar
      vertebrae revealed delayed or incomplete endochondral ossification. Comparative
      histology and immunohistochemistry (IHC) analyses further verified the effects of
      CypA deficiency on chondrogenic differentiation. Our results provide evidence for
      the important contribution of CypA as a pertinent component acting through NF
      kappaB-Sox9 in regulation of chondrogenesis signaling. These findings are
      important to better understand signal-induced chondrogenesis of chondrogenic
      progenitors in physiological and pathophysiological contexts. 

PMID- 25870111
TI  - SMAD1 and SMAD5 Expression Is Coordinately Regulated by FLI1 and GATA2 during
      Endothelial Development.
AB  - The bone morphogenetic protein (BMP)/SMAD signaling pathway is a critical
      regulator of angiogenic sprouting and is involved in vascular development in the
      embryo. SMAD1 and SMAD5, the core mediators of BMP signaling, are vital for this
      activity, yet little is known about their transcriptional regulation in
      endothelial cells. Here, we have integrated multispecies sequence conservation,
      tissue-specific chromatin, in vitro reporter assay, and in vivo transgenic data
      to identify and validate Smad1+63 and the Smad5 promoter as tissue-specific cis
      regulatory elements that are active in the developing endothelium. The activity
      of these elements in the endothelium was dependent on highly conserved ETS, GATA,
      and E-box motifs, and chromatin immunoprecipitation showed high levels of
      enrichment of FLI1, GATA2, and SCL at these sites in endothelial cell lines and
      E11 dorsal aortas in vivo. Knockdown of FLI1 and GATA2 but not SCL reduced the
      expression of SMAD1 and SMAD5 in endothelial cells in vitro. In contrast, CD31(+)
      cKit(-) endothelial cells harvested from embryonic day 9 (E9) aorta-gonad
      mesonephros (AGM) regions of GATA2 null embryos showed reduced Smad1 but not
      Smad5 transcript levels. This is suggestive of a degree of in vivo selection
      where, in the case of reduced SMAD1 levels, endothelial cells with more robust
      SMAD5 expression have a selective advantage. 

PMID- 25870114
TI  - Midterm results of stemless shoulder arthroplasty: a prospective study.
AB  - BACKGROUND: This study evaluated the functional and radiologic results of
      shoulder arthroplasty using a single type of stemless humeral head implant with a
      minimum follow-up of 5 years. METHODS: Stemless shoulder arthroplasties in 78
      patients at a mean age of 58 years were prospectively evaluated at a mean
      clinical and radiologic follow-up of 72 months. Functional results were
      documented using the age- and sex-adjusted Constant score with standardized
      radiographic examination. RESULTS: The Constant score improved significantly from
      38.1% to 75.3% (P < .0001). Active range of motion improved significantly for
      flexion (from 114 degrees  to 141 degrees ), abduction (from 74 degrees  to 130
      degrees ), and external rotation (from 25 degrees  to 44 degrees ; P < .0001).
      Bone mineral density was reduced in 34.9% of the older population, without an
      influence on shoulder function (Constant score without lowering of bone density;
      73%; Constant score with lowering of bone density 80%; P = .404). The overall
      complication rate was 12.8%, with an overall revision rate of 9%. None of the
      stemless implants were revised for loosening. CONCLUSION: The functional and
      radiologic results of the stemless shoulder arthroplasty are comparable to the
      third and fourth generation of standard stem arthroplasty.

PMID- 25870113
TI  - Risk for Depression and Anxiety in Youth: The Interaction between Negative
      Affectivity, Effortful Control, and Stressors.
AB  - Theories of temperament suggest that individual differences in affective
      reactivity (e.g., negative affectivity) may confer risk for internalizing
      psychopathology in youth and that self-regulatory aspects of temperament (e.g.,
      effortful control) may protect against the deleterious effects of high negative
      affective reactivity. However, no study to date has examined how the relationship
      between temperament and youth internalizing psychopathology may be moderated by
      stress. The current study used a prospective longitudinal design to test the
      interaction of temperament (e.g., negative affectivity and effortful control) and
      stressors as a predictor of youth (ages 7-16; 56 % female; N = 576) depressive
      and anxious symptoms over a 3-month period. Findings show that at low levels of
      stress, high levels of effortful control protect against the development of
      depressive and anxious symptoms among youth with high levels of negative
      affectivity. However, at high levels of stress, this buffering effect is not
      observed. Gender and grade did not moderate this relationship. Overall, findings
      extend current understanding of how the interaction of individual psychosocial
      vulnerabilities and environmental factors may confer increased or decreased risk
      for depressive and anxious symptoms.

PMID- 25870116
TI  - Late-Stage Functionalization of 1,2-Dihydro-1,2-azaborines via Regioselective
      Iridium-Catalyzed C-H Borylation: The Development of a New N,N-Bidentate Ligand
      Scaffold.
AB  - The first general late-stage functionalization of monocyclic 1,2-azaborines at
      the C(6) position is described. Ir-catalyzed C-H borylation occurs
      regioselectively at the C(6) position of B-substituted 1,2-azaborines and is
      compatible with a range of substitution patterns at boron (e.g., hydride,
      alkoxide, alkyl, and aryl substituents). Subsequent Suzuki cross coupling with
      aryl- and heteroaryl bromides furnishes 1,2-azaborine-based biaryl compounds
      including 6-[pyrid-2-yl]-1,2-azaborines that represent novel kappa(2)-N,N
      bidentate ligands. The 6-[pyrid-2-yl]-B-Me-1,2-azaborine ligand has been
      demonstrated to form an emissive coordination complex with dimesitylboron that
      exhibits bathochromically shifted absorption and emission maxima and a higher
      photoluminescence quantum yield compared to its carbonaceous analogue. 

PMID- 25870112
TI  - Mcm2-7 Is an Active Player in the DNA Replication Checkpoint Signaling Cascade
      via Proposed Modulation of Its DNA Gate.
AB  - The DNA replication checkpoint (DRC) monitors and responds to stalled replication
      forks to prevent genomic instability. How core replication factors integrate into
      this phosphorylation cascade is incompletely understood. Here, through analysis
      of a unique mcm allele targeting a specific ATPase active site (mcm2DENQ), we
      show that the Mcm2-7 replicative helicase has a novel DRC function as part of the
      signal transduction cascade. This allele exhibits normal downstream mediator
      (Mrc1) phosphorylation, implying DRC sensor kinase activation. However, the
      mutant also exhibits defective effector kinase (Rad53) activation and classic DRC
      phenotypes. Our previous in vitro analysis showed that the mcm2DENQ mutation
      prevents a specific conformational change in the Mcm2-7 hexamer. We infer that
      this conformational change is required for its DRC role and propose that it
      allosterically facilitates Rad53 activation to ensure a replication-specific
      checkpoint response. 

PMID- 25870115
TI  - Prevalence of calcific deposits within the rotator cuff tendons in adults with
      and without subacromial pain syndrome: clinical and radiologic analysis of 1219
      patients.
AB  - BACKGROUND: Calcific tendinopathy is one of the most frequent causes of pain in
      the shoulder and is characterized by the presence of calcific deposits in the
      rotator cuff; however, calcific deposits have also been described in asymptomatic
      individuals. Only a few authors have reported epidemiologic data on the
      prevalence of calcific deposits in the rotator cuff. METHODS: This study analyzed
      clinical and radiological data of 1219 adults with and without subacromial pain
      syndrome (SAPS) to assess the prevalence of calcific deposits in the rotator
      cuff. Multivariate analysis was used to define risk factors associated with the
      presence of symptomatic calcific tendinopathy. RESULTS: Calcific deposits were
      found in the rotator cuff of 57 of 734 asymptomatic patients (7.8%). Of 485
      patients with SAPS, 42.5% had calcific deposits. Age between 30 and 60 years
      (odds ratio [OR], 8.0; 95% confidence interval [CI], 2.5-26.3; P < .001),
      subacromial pain (OR, 7.1; 95% CI, 5.1-9.9, P < .001), and female gender (OR,
      1.5; 95% CI, 1.1-2.0; P = .014) were significantly associated with increased odds
      of calcific deposits. CONCLUSION: This study demonstrates that women aged between
      30 and 60 years with SAPS and a calcific deposit of >1.5 cm in length have the
      highest chance of suffering from symptomatic calcific tendinopathy of the rotator
      cuff. The prevalence rates of 7.8% in asymptomatic patients and 42.5% in patients
      with SAPS provide a current view on the epidemiology of calcific deposits in the
      rotator cuff.

PMID- 25870117
TI  - Development and validation of a VISA tendinopathy questionnaire for greater
      trochanteric pain syndrome, the VISA-G.
AB  - BACKGROUND: Greater trochanteric pain syndrome (GTPS) is common, resulting in
      significant pain and disability. There is no condition specific outcome score to
      evaluate the degree of severity of disability associated with GTPS in patients
      with this condition. OBJECTIVE: To develop a reliable and valid outcome
      measurement capable of evaluating the severity of disability associated with
      GTPS. METHODS: A phenomenological framework using in-depth semi structured
      interviews of patients and medical experts, and focus groups of physiotherapists
      was used in the item generation. Item and format clarification was undertaken via
      piloting. Multivariate analysis provided the basis for item reduction. The
      resultant VISA-G was tested for reliability with the inter class co-efficient
      (ICC), internal consistency (Cronbach's Alpha), and construct validity
      (correlation co-efficient) on 52 naive participants with GTPS and 31 asymptomatic
      participants. RESULTS: The resultant outcome measurement tool is consistent in
      style with existing tendinopathy outcome measurement tools, namely the suite of
      VISA scores. The VISA-G was found to be have a test-retest reliability of ICC2,1
      (95% CI) of 0.827 (0.638-0.923). Internal consistency was high with a Cronbach's
      Alpha of 0.809. Construct validity was demonstrated: the VISA-G measures
      different constructs than tools previously used in assessing GTPS, the Harris Hip
      Score and the Oswestry Disability Index (Spearman Rho:0.020 and 0.0205
      respectively). The VISA-G did not demonstrate any floor or ceiling effect in
      symptomatic participants. CONCLUSION: The VISA-G is a reliable and valid score
      for measuring the severity of disability associated GTPS.

PMID- 25870118
TI  - Interleukin-1alpha activation and localization in lipopolysaccharide-stimulated
      human monocytes and macrophages.
AB  - BACKGROUND: Interleukin-1alpha (IL-1alpha) is a proinflammatory cytokine
      belonging to the IL-1 family. It is synthesized as a 33kDa precursor peptide that
      is cleaved by a calpain-like protease to a 16 kDa propiece and a 17 kDa mature IL
      1alpha peptide. In contrast to its close relative, IL-1beta, the role of IL
      1alpha in inflammation is only partly understood. RESULTS: Human monocyte derived
      macrophages, stimulated with lipopolysaccharide (LPS) were analysed for
      production and localization of IL-1alpha by use of a monoclonal antibody (MAb)
      generated against recombinant precursor IL-1alpha. We found that the MAb detected
      IL-1alpha within the nuclei of the cells 2h (hours) after LPS stimulation and
      production continued for up to 20 h. At no time could we demonstrate cleavage of
      the IL-1alpha precursor. The MAb was conjugated to fluorescein isothiocyanate
      (FITC) for use in flow cytometry. Based on the flow cytometric analysis CD68
      positive cells were positive for IL-1alpha in agreement with CD68 being a marker
      for monocytes. CONCLUSIONS: Here, we demonstrate, for the first time, a method to
      visualize and measure the production of IL-1alpha in both human monocytes and
      macrophages.

PMID- 25870119
TI  - 'From scared to prepared': targeted structured induction training during the
      transition from medical school to foundation doctor.
AB  - The risks to patients at August handover time are well known, yet there is no
      national consensus on the best way to deliver induction programmes for Foundation
      Year One (F1). The aim of this study was to design, deliver and assess a targeted
      structured induction programme for new F1 doctors. The induction training
      programme was designed using educational models of topic analysis informed by
      results of a survey of F1s and medical students, and the F1 curriculum. Data
      regarding serious untoward incidents and self-reported preparedness were
      collected between 2008 and 2010, and rates were compared between those receiving
      optional (2008) and compulsory (2009 and 2010) training. By delivering targeted
      education and spending time with the outgoing F1 doctors, 97 % of our new doctors
      felt adequately prepared for practice. The incidence of self-reported mistakes
      made by F1s in the first 4 months of their practice fell by 45 % and serious
      untoward incidents also decreased. Targeted structured induction training
      addresses final-year medical students' concerns about their preparedness for
      practice as junior doctors, and improves patient safety. This study supports the
      General Medical Council recommendation that targeted structured induction
      training should be mandatory for all new doctors. 

PMID- 25870120
TI  - Basal cell carcinoma of the prostate is an aggressive tumor with frequent loss of
      PTEN expression and overexpression of EGFR.
AB  - Basal cell carcinoma (also referred to as adenoid cystic carcinoma) is a rare
      tumor of the prostate. Although largely characterized as indolent, poor outcomes
      have been reported in a considerable fraction of cases. As yet, optimum treatment
      strategies for this cancer have not been developed. This study investigates
      protein expression of common or potential molecular therapeutic targets and
      reports on the clinicopathological features of 9 new cases. We evaluated the
      expression of ERBB2, KIT, androgen receptor, PTEN, EGFR, ERG, and p53 via
      immunohistochemistry. We also examined EGFR amplification and TMPRSS2-ERG gene
      rearrangement by fluorescence in situ hybridization. The mean clinical follow-up
      was 44 months. We found that basal cell carcinoma behaved aggressively with
      almost one-half of the cases displaying high-risk pathologic features or local
      recurrence (44%). One patient died as a result of metastatic disease. The most
      consistent abnormalities included a loss of PTEN expression (56% of cases) and
      EGFR overexpression (67% of cases). EGFR overexpression occurred in the absence
      of gene amplification. The TMPRSS2-ERG rearrangement was not detected in any of
      the tumors studied, nor was ERG protein positivity identified by immunostaining.
      In addition, ERBB2, KIT, p53, and androgen receptor expressions were either
      absent or showed only weak, limited reactivity. Our results suggest that there is
      a high morbidity associated with this tumor, and more intense follow-up and
      additional treatment may be indicated. Furthermore, targeted therapies directed
      against the EGFR and PTEN proteins or their constitutive pathways may be
      promising for future clinical management. 

PMID- 25870121
TI  - Pancreatic adenocarcinoma up-regulated factor expression is associated with
      disease-specific survival in cervical cancer patients.
AB  - Pancreatic adenocarcinoma up-regulated factor (PAUF) is a novel soluble protein
      involved in tumor development and metastases. This study was to investigate the
      PAUF expression and its prognostic value in cervical cancer patients. The
      expression of PAUF was immunohistochemically determined in 345 formalin-fixed,
      paraffin-embedded cervical cancer tissues and 107 normal cervical epitheliums.
      Subsequently, its associations with clinicopathological characteristics and
      patient survival were assessed. PAUF protein was expressed both in cytoplasm and
      nucleus, and cytoplasmic expression was more frequent in cancers than normal
      tissues (32% versus 17%, P = .002), and the difference was prominent in glandular
      cells. Notably, the expression was more frequent in adenocarcinoma than in
      squamous cell carcinoma (57% versus 25%, respectively; P < .001), and the
      differential expression was also seen at the messenger RNA level (P = .014). Cox
      regression analysis showed that the cytoplasmic expression of PAUF protein was
      independently associated with poor disease-free (hazard ratio = 2.3; 95%
      confidence interval, 1.2-4.3; P = .008) and overall survival (hazard ratio = 2.9;
      95% confidence interval, 1.2-7.5; P = .020). Detection of PAUF expression may aid
      current evaluation of prognosis in cervical adenocarcinoma. 

PMID- 25870122
TI  - Activation of the Macrophage alpha7 Nicotinic Acetylcholine Receptor and Control
      of Inflammation.
AB  - Inflammatory responses to stimuli are essential body defenses against foreign
      threats. However, uncontrolled inflammation may result in serious health
      problems, which can be life-threatening. The alpha7 nicotinic acetylcholine
      receptor, a ligand-gated ion channel expressed in the nervous and immune systems,
      has an essential role in the control of inflammation. Activation of the
      macrophage alpha7 receptor by acetylcholine, nicotine, or other agonists,
      selectively inhibits production of pro-inflammatory cytokines while leaving anti
      inflammatory cytokines undisturbed. The neural control of this regulation pathway
      was discovered recently and it was named the cholinergic anti-inflammatory
      pathway (CAP). When afferent vagus nerve terminals are activated by cytokines or
      other pro-inflammatory stimuli, the message travels through the afferent vagus
      nerve, resulting in action potentials traveling down efferent vagus nerve fibers
      in a process that eventually leads to macrophage alpha7 activation by
      acetylcholine and inhibition of pro-inflammatory cytokines production. The
      mechanism by which activation of alpha7 in macrophages regulates pro-inflammatory
      responses is subject of intense research, and important insights have thus been
      made. The results suggest that activation of the macrophage alpha7 controls
      inflammation by inhibiting NF-kappaB nuclear translocation, and activating the
      JAK2/STAT3 pathway among other suggested pathways. While the alpha7 is well
      characterized as a ligand-gated ion channel in neurons, whole-cell patch clamp
      experiments suggest that alpha7's ion channel activity, defined as the
      translocation of ions across the membrane in response to ligands, is absent in
      leukocytes, and therefore, ion channel activity is generally assumed not to be
      required for the operation of the CAP. In this perspective, we briefly review
      macrophage alpha7 activation as it relates to the control of inflammation, and
      broaden the current view by providing single-channel currents as evidence that
      the alpha7 expressed in macrophages retains its ion translocation activity
      despite the absence of whole-cell currents. Whether this ion-translocating
      activity is relevant for the proper operation of the CAP or other important
      physiological processes remains obscure. 

PMID- 25870123
TI  - Interactions between macro- and micro-circulation: are they relevant?
AB  - Macrovasculature, microvasculature, and the heart are the main determinants of
      the structure and function of the circulatory system. Due to viscoelastic
      properties of large arteries, the pulsatile pressure and flow that result from
      intermittent ventricular ejection are smoothed out, so that microvasculature
      mediates steadily the delivery of nutrients and oxygen to tissues. The disruption
      of this function, which occurs when microvascular structure develops, mainly in
      response to hypertension, leads to end-organ damage. Microvascular structure is
      not only the site of vascular resistance but probably also the origin of most of
      the wave reflections generating increased central systolic blood pressure in the
      elderly. Many data of the literature suggest that hypertension-related damage to
      the micro and macrovascular system may be corrected by pharmacological agents.
      Among them, beta-blocking agents and diuretics have a negligible effect on
      microvascular structure, while renin-angiotensin system antagonists and calcium
      entry blockers have favorable actions, improving large artery mechanics and
      possibly reducing central wave reflections. Central pulse pressure, indicative of
      changes in large conduit arteries is an independent determinant of vascular
      remodelling in small resistance arteries and might represent a main target of
      antihypertensive treatment. 

PMID- 25870124
TI  - Effects of a new combination of nutraceuticals with Morus alba on lipid profile,
      insulin sensitivity and endotelial function in dyslipidemic subjects. A cross
      over, randomized, double-blind trial.
AB  - INTRODUCTION: Nutraceuticals (NUT) are forms of compounds with biological
      activity commonly used to improve health in dosage largely exceeding those
      obtainable in food. AIM: We compared, in a double blind randomized cross-over
      trial, the effects of two NUT combinations on the control of glico-lipidic
      metabolism in patients with hypercholesterolemia not on statins. METHODS: At
      study start patients were given dietary counseling and received placebo for 2
      weeks. After this run-in period, patients were randomized: (1) Combination A
      [Policosanol, Red yeast rice (Monakolin K 3 mg), Berberine 500 mg, Astaxantine,
      Folic Acid and Coenzyme Q10] for 4 weeks followed by 4 weeks of Combination B
      [Red yeast rice (Monakolin K 3.3 mg), Berberine 531.25 mg and leaf extract of
      Morus alba]; (2) Combination B for 4 weeks followed by 4 weeks of Combination A.
      RESULTS: Combination B reduced LDL cholesterol below 130 mg/dl in 56.5 % of the
      patients, and Cambination A only in 21.7 % of them (p <= 0.027). Both treatments
      reduced plasma levels of triglycerides, total and LDL cholesterol and increased
      HDL cholesterol (all p < 0.03). Total and LDL cholesterol reduction was more
      pronounced in patients taking Combination B (p < 0.005). Combination B reduced
      also glycated hemoglobin, fasting glucose and insulin plasma levels as well as
      HOMA index (p < 0.005). CONCLUSIONS: An increased content of Berberin and
      Monacolin K and the addition of Morus alba extract improves the effect on plasma
      cholesterol and on glucose metabolism of the NUT Combination. These effects may
      allow the speculation of a more marked improvement in cardiovascular prognosis.

PMID- 25870126
TI  - Enhanced field emission from in situ synthesized 2D copper sulfide nanoflakes at
      low temperature by using a novel controllable solvothermal preferred edge growth
      route.
AB  - A facile one-pot solvothermal route using the reaction of sputtered copper film
      and sulfur powder in ethanol solution at a low temperature of 90  degrees C for
      12 hours has been implemented to in situ synthesize 2D hexagonal copper sulfide
      (CuS) nanoflakes. Their field electron emission (FE) characteristics were
      investigated and were found to have a close relationship with the copper film's
      thickness. The lowest turn on electric field (Eon) was 2.05 V MUm(-1) and the
      largest field enhancement factor (beta) was 7261 when the copper film's thickness
      was 160 nm. Furthermore, through a preferred edge growth route, patterned CuS
      nanoflakes were synthesized with the combined effect from a copper film seed
      layer and a passivation layer to further improve FE properties with an Eon of
      1.65 V MUm(-1) and a beta of 8351. The mechanism of the patterned CuS nanoflake
      preferred edge growth is reported and discussed for the first time. 

PMID- 25870125
TI  - Two rare cases of laryngeal intralymphatic histiocytosis.
AB  - We report two rare cases of intralymphatic histiocytosis causing, respectively,
      recurrent and persistent episodes of upper airway swelling and breathing
      difficulties. Case 1 was a 39-year-old man who was referred with recurrent upper
      airway swelling causing difficulty in breathing. A direct laryngoscopy was
      performed under general anesthesia due to minimal effect from treatment with
      antibiotics and anti-oedema medication. On examination, the larynx was found to
      be swollen and oedematous but not inflamed. Biopsies from the aryepiglottic folds
      showed intralymphatic histiocytosis. The patient was extensively examined but the
      only abnormal finding was a low CD4 count. The breathing difficulties fluctuated
      during the diagnostic process and settled after a year. Case 2 was a 35-year-old
      man who presented with persistent laryngeal swelling. Biopsies from the
      epiglottis showed intralymphatic histiocytosis. Extensive investigations were
      performed but discovered no abnormal findings. He received CO2 laser treatment
      twice and the swelling decreased. Intralymphatic histiocytosis is extremely rare
      in upper airway pathology. It is an important differential diagnosis in patients
      with recurrent and chronic laryngeal swelling and dyspnoea. 

PMID- 25870127
TI  - Azimuthal sound localization in the European starling (Sturnus vulgaris): III.
      Comparison of sound localization measures.
AB  - Sound localization studies have typically employed two types of tasks: absolute
      tasks that measured the localization of the angular location of a single sound
      and relative tasks that measured the localization of the angular location of a
      sound relative to the angular location of another sound from a different source
      (e.g., in the Minimum Audible Angle task). The present study investigates the
      localization of single sounds in the European starling (Sturnus vulgaris) with a
      left/right discrimination paradigm. Localization thresholds of 8-12 degrees 
      determined in starlings using this paradigm were much lower than the minimum
      audible angle thresholds determined in a previous study with the same
      individuals. The traditional concept of sound localization classifies the present
      experiment as an absolute localization task. However, we propose that the
      experiment presenting single sounds measured localization of the angular location
      of the sound relative to a non-acoustic spatial frame of reference. We discuss
      how the properties of the setup can determine if presentation of single sounds in
      a left/right discrimination paradigm comprises an absolute localization task
      rather than a localization task relative to a non-acoustic reference.
      Furthermore, the analysis methods employed may lead to quite different threshold
      estimates for the same data, especially in case of a response bias in left/right
      discrimination. We propose using an analysis method precluding effects of
      response bias on the threshold estimate. 

PMID- 25870128
TI  - A Call to Action for Care Coordination Research and Pediatric Implementation
      Science.

PMID- 25870129
TI  - Characteristics of intracranial pressure (ICP) waves and ICP in children with
      treatment-responsive hydrocephalus.
AB  - BACKGROUND: One important goal of modern treatment of pediatric hydrocephalus is
      to normalize the intracranial pressure (ICP) and ICP volume reserve capacity to
      optimize normal brain development. Better knowledge of the characteristics of ICP
      waves/ICP in pediatric hydrocephalus may provide new insight into the mechanisms
      behind modern hydrocephalus treatment. The aim of the present work was to
      characterize the ICP waves/ICP in children with either communicating or non
      communicating hydrocephalus who improved clinically after surgery. The
      hydrocephalic children not treated surgically following ICP monitoring served as
      reference patients. METHODS: The patient material includes all children with
      hydrocephalus and no previous surgical treatment who underwent diagnostic ICP
      wave/ICP monitoring during the period 2002-2011. We retrieved the information
      about the patients from the patient records and the digitally stored ICP
      waveforms. The ICP wave characteristics amplitude, rise time and rise time
      coefficient and the mean ICP were determined in the patients treated surgically
      for their hydrocephalus. The findings were compared with findings in children not
      treated surgically after ICP monitoring who served as reference patients.
      RESULTS: The patient material includes 58 patients. Thirty-one (53%) were treated
      surgically after ICP monitoring, of whom all improved clinically. As compared to
      the reference patients, patients treated surgically presented with increased ICP
      wave amplitudes (MWA) and mean ICP. Alterations were comparable in communicating
      and non-communicating hydrocephalus. We found no apparent association between the
      ICP wave/ICP scores and presence of symptoms, indices of ventricular size or age.
      CONCLUSIONS: Children with either communicating or non-communicating
      hydrocephalus improving clinically after surgery presented with elevated MWA and
      mean ICP. In particular, the levels of MWA were raised to a magnitude seen when
      intracranial compliance is impaired. Hence, the present observations may support
      the idea that improvement of intracranial compliance can be an important
      mechanism by which shunts work in pediatric hydrocephalus.

PMID- 25870130
TI  - Dumb-bell mass straddling the ridge of petrous: an atypical presentation of
      mucormycosis.

PMID- 25870131
TI  - Sulfamic acid promoted one-pot three-component synthesis and cytotoxic evaluation
      of spirooxindoles.
AB  - A simple, mild and efficient method for the synthesis of pyrazolopyridine based
      spirooxindoles by the three-component reaction has been developed using sulfamic
      acid (H2NSO3H) as a green catalyst. The method involves use of water as a solvent
      which makes it eco-friendly. The catalyst used is readily available and is
      prominent for short reaction time, operational simplicity and high yields. After
      completion of the reaction the catalyst could be recovered and reused for up to
      four cycles without loss in catalytic activity. Employing this method a library
      of 34 compounds has been synthesized and investigated for their cytotoxicity
      against a panel of three human cancer cell lines. Some of the compounds like 4o
      and 4p exhibited remarkable cytotoxicities with IC50 values of 0.35MUM and
      1.92MUM against MDA-MB-231 cell line. 

PMID- 25870132
TI  - Discovery and hit-to-lead optimization of 2,6-diaminopyrimidine inhibitors of
      interleukin-1 receptor-associated kinase 4.
AB  - Interleukin receptor-associated kinase 4 (IRAK4) is a critical element of the
      Toll-like/interleukin-1 receptor inflammation signaling pathway. A screening
      campaign identified a novel diaminopyrimidine hit that exhibits weak IRAK4
      inhibitory activity and a ligand efficiency of 0.25. Hit-to-lead activities were
      conducted through independent SAR studies of each of the four pyrimidine
      substituents. Optimal activity was observed upon removal of the pyrimidine C-4
      chloro substituent. The intact C-6 carboribose is required for IRAK4 inhibition.
      Numerous heteroaryls were tolerated at the C-5 position, with azabenzothiazoles
      conferring the best activities. Aminoheteroaryls were preferred at the C-2
      position. These studies led to the discovery of inhibitors 35, 36, and 38 that
      exhibit nanomolar inhibition of IRAK4, improved ligand efficiencies, and modest
      kinase selectivities. 

PMID- 25870133
TI  - Synthesis and characterization of gadolinium-Peptidomimetic complex as an
      alphavbeta3 integrin targeted MR contrast agent.
AB  - There is growing interest in small and rigid peptidomimetic alphavbeta3 integrin
      antagonists that are readily synthesized and characterized and amenable to
      physiological conditions. Peptidomimetic 4-[2-(3,4,5,6-tetrahydropyrimidine-2
      ylamino)ethyloxy]benzoyl-2-[N-(3-amino-neopenta-1-carbamyl)]-aminoethylsulfonyl
      amino-beta-alanine (IAC) was successfully conjugated to DOTA, complexed with
      Gd(III) and radiolabeled with (153)Gd. Radioassay results demonstrated
      specificity of the labeled conjugate by blocking ~95% binding with the addition
      of a 50-fold molar excess of cold IAC to the reaction solution. Relaxometry was
      used to support the hypothesis that the specificity of the Gd-peptidomimetic
      targeting alphavbeta3 integrin would increase the contrast and therefore enhance
      the sensitivity of an MRI scan of alphavbeta3 integrin positive tissues. Magnetic
      resonance imaging of cell pellets (M21 human melanoma) was also performed, and
      the images clearly show that cells reacted with Gd(III)-DOTA-IAC display a
      brighter image than cells without the Gd(III)-DOTA-IAC contrast agent. In
      addition, Gd(III)-DOTA-IAC and IAC, with IC50 of 300nM and 230nM, respectively,
      are 2.1 and 2.7 times more potent than c(RGDfK) whose IC50 is 625nM. This
      promising preliminary data fuels further investigation of DOTA-IAC conjugates for
      targeting tumor associated angiogenesis and alphavbeta3 integrin positive tumors
      using magnetic resonance imaging. 

PMID- 25870134
TI  - Bacterial profiles and proteolytic activity in peri-implantitis versus healthy
      sites.
AB  - Peri-implantitis is a biofilm-induced destructive inflammatory process that, over
      time, results in loss of supporting bone around an osseointegrated dental
      implant. Biofilms at peri-implantitis sites have been reported to be dominated by
      Gram-negative anaerobic rods with a proteolytic metabolism such as,
      Fusobacterium, Porphyromonas, Prevotella and Tannerella, as well as anaerobic
      Gram-positive cocci. In this study, we hypothesized that protease activity is
      instrumental in driving bone destruction and we therefore compared the microbial
      composition and level of protease activity in samples of peri-implant biofluid
      (PIBF) from 25 healthy subjects (H group) and 25 subjects with peri-implantitis
      (PI group). Microbial composition was investigated using culture techniques and
      protease activity was determined using a FITC-labelled casein substrate. The
      microbial composition was highly variable in subjects both in the H and PI groups
      but one prominent difference was the prevalence of Porphyromonas/Prevotella and
      anaerobic Gram positive cocci which was significantly higher in the PI than in
      the H group. A subgroup of subjects with peri-implantitis displayed a high level
      of protease activity in the PIBF compared to healthy subjects. However, this
      activity could not be related to the presence of specific bacterial species. We
      propose that a high level of protease activity may be a predictive factor for
      disease progression in peri-implantitis. Further longitudinal studies are however
      required to determine whether assessment of protease activity could serve as a
      useful method to identify patients at risk for progressive tissue destruction. 

PMID- 25870135
TI  - Development of a triplex real-time PCR assay for the simultaneous detection of
      Clostridium beijerinckii, Clostridium sporogenes and Clostridium tyrobutyricum in
      milk.
AB  - Clostridium beijerinckii, Clostridium sporogenes and Clostridium tyrobutyricum
      are considered the leading bacteria implicated in late blowing defects affecting
      semi-hard and hard cheese production. The aim of this study was to develop a
      multiplex Real-Time PCR (qPCR) analysis for a rapid and simultaneous detection of
      C. beijerinckii, C. sporogenes and C. tyrobutyricum, using specific primers
      respectively targeting the nifH, gerAA and enr genes. The limits of detection in
      raw milk were 300 CFU/50 mL in the case of C. beijerinckii, 2 CFU/50 mL for C.
      sporogenes and 5 CFU/50 mL for C. tyrobutyricum spores. The qPCR method was
      applied to artificially contaminated raw milk samples, and molecular
      quantification showed good correlation (R(2) = 0.978) with microbiological
      counting. Our results demonstrate that this method, combined with a DNA
      extraction protocol optimized for spore lysis, could be a useful tool for the
      direct quantification of the considered clostridia species. 

PMID- 25870136
TI  - Synthesis, Single X-ray Crystal, Spectroscopic and Photophysical Studies of Novel
      Heterocyclic Chalcones with Their Biological Application.
AB  - Chalcones were synthesized by reaction of 3-acetyl-2,5-dimethylfuran with
      corresponding active aldehyde in ethanolic NaOH. The structure of these compounds
      was established by elemental analysis, IR, (1)H-NMR, (13)C-NMR and EI-MS spectral
      analysis. UV-vis and fluorescence spectroscopy measurements provided that
      compounds are good absorbent and fluorescent. Fluorescence polarity study
      demonstrated that the compounds were sensitive to the polarity of the
      microenvironment provided by deferent solvents. In addition, spectroscopic and
      physicochemical parameters, including electronic absorption, extenction
      coefficient, Stokes shift, oscillator strength and transition dipole moment were
      investigated in order to explore the analytical potential of synthesized
      compounds. The anti-bacterial activity of the compounds were first tested in
      vitro by the disk diffusion assay against two Gram-positive and two Gram-negative
      bacteria, and then the minimum inhibitory concentration (MIC) was determined with
      the reference of standard drug Tetracycline. The results showed that compound 3
      is better inhibitors of both types of the bacteria (Gram-positive and Gram
      negative) as compared to tetracycline. Graphical Abstract ?. 

PMID- 25870137
TI  - Pharmacogenetic Markers of Drug Efficacy and Toxicity.
AB  - The action of a drug is dictated by its pharmacokinetic and pharmacodynamics
      properties, both of which can vary in different individuals because of
      environmental and genetic factors. Pharmacogenetics, the study of genetic factors
      determining drug response, has the potential to improve clinical outcomes through
      targeting therapies, individualizing dosing, preventing adverse drug reactions,
      and potentially rescuing previously failed therapies. Although there have been
      significant advances in pharmacogenetics over the last decade, only a few have
      been translated into clinical practice. However, with new rapid genotyping
      technologies, regulatory modernization, novel clinical trial designs, systems
      approaches, and integration of pharmacogenetic data into decision support
      systems, there is hope that pharmacogenetics, as an important component of the
      overall drive towards personalized medicine, will advance more quickly in the
      future. There will continue to be a need for collaboration between centers all
      over the world, and multisector working, capitalizing on the current data
      revolution. 

PMID- 25870138
TI  - Hand hygiene compliance monitoring: the state of the art.
AB  - Hand hygiene is crucial to prevent transmission of hospital-acquired infections.
      The WHO recommends five moments for hand hygiene: (1) before patient contact, (2)
      before performing an aseptic task, (3) after exposure with body fluids, (4) after
      patient contact, and (5) after contact with patient's surroundings. Nevertheless,
      hand hygiene compliance rates remain low among healthcare workers. Direct
      observation is the gold standard method for hand hygiene monitoring; however, it
      is time consuming and observer dependent. Technology has allowed the development
      of several other hand hygiene surveillance methods. In this article, we review
      the different modalities for hand hygiene compliance monitoring. 

PMID- 25870139
TI  - The Challenges and Promise of HIV-Infected Donors for Solid Organ
      Transplantation.
AB  - Solid organ transplantation is now the standard of care for many HIV-infected
      patients with end-stage kidney or liver disease. There is an overall organ
      shortage that affects all transplant candidates, including those with HIV. The
      use of HIV-infected donors could help alleviate this shortage. The precedent for
      this approach was set in South Africa, where promising short-term outcomes have
      been reported in a limited number of HIV-infected recipients of kidney
      transplants from HIV-infected donors. As a consequence, the HIV Organ Policy
      Equity (HOPE) Act was passed in the United States, legalizing research into HIV
      infected organ donation. In this review, we discuss some of the key issues
      related to HIV-infected organ donation, including the need for transplant in HIV
      infected populations, characterization of the potential donor pool in the USA,
      criteria for donor selection, concerns specific to the HIV-infected donor, the
      ethics of HIV-infected organ donation, and the next steps toward making HIV
      infected donation a reality in the USA. 

PMID- 25870140
TI  - Live virus vaccines in transplantation: friend or foe?
AB  - Solid organ and hematopoietic stem cell transplant recipients may be exposed to
      diseases which may be prevented through live attenuated virus vaccines (LAVV).
      Because of their immunosuppression, these diseases can lead to severe
      complications in transplant recipients. Despite increasing evidence regarding the
      safety and effectiveness of certain LAVV, these vaccines are still
      contraindicated for immunocompromised patients, such as transplant recipients. We
      review the available studies on LAVV, such as varicella zoster, measles-mumps
      rubella, influenza, yellow fever, polio, and Japanese encephalitis vaccines in
      transplant patients. We discuss the current recommendations and the potential
      risks, as well as the expected benefits of LAVV immunization in this population. 

PMID- 25870141
TI  - Transplant tourism: understanding the risks.
AB  - Transplant tourism is commonly defined as travel abroad for the purpose of
      transplantation, but the term evokes ethical and legal concerns about commercial
      transplantation. Due to the mismatch in supply and demand for organs, transplant
      tourism has increased over the last several decades and now accounts for 10 % of
      transplants worldwide. Patients from the USA who pursue transplantation abroad do
      so most commonly for renal transplantation, and travel mostly to China, the
      Philippines, and India. Transplant tourism puts the organ recipient at risk for
      surgical complications, poor graft outcome, increased mortality, and a variety of
      infectious complications. Bacterial, viral, fungal, and parasitic infections have
      all been described, and most concerning are the high rates of blood-borne viral
      infections and invasive, often fatal, fungal infections. Transplant and
      infectious diseases physicians should have a high degree of suspicion for
      infectious complications in patients returning from transplantation abroad. 

PMID- 25870142
TI  - Imaging in Neurologic Infections II: Fungal and Viral Diseases.
AB  - Infections of the nervous system have a significant impact on global mortality
      and morbidity. These infections are medical emergencies that are frequently
      diagnostically challenging. Incorporation of neuroimaging can be essential for
      early diagnosis and initiation of proper treatment. In this second part of this
      two-part review, we focus on diagnostic imaging features of selected fungal and
      viral nervous system infections. 

PMID- 25870143
TI  - Value of solid organ transplant-trained pharmacists in transplant infectious
      diseases.
AB  - Advances in organ transplantation have led to improved graft and patient
      survival. Transplant pharmacist's education and training uniquely position them
      to contribute knowledge and skills to the management of these highly complex
      patients. In 2004, the United Network for Organ Sharing bylaws added requirements
      that all transplant programs identify one or more pharmacists with experience in
      transplant pharmacotherapy to be responsible for providing pharmaceutical care to
      solid organ transplant recipients. These bylaws also delineated the transplant
      pharmacist's roles and responsibilities. To further support these efforts, in
      2007 the Centers for Medicare and Medicaid Services accreditation standards for
      transplant centers also mandated that a center have a designated, qualified
      expert in transplant pharmacology as a multidisciplinary team member. The
      transplant pharmacist is a consistent member of the transplant team that can add
      value to the multidisciplinary approach of prevention and treatment of transplant
      infectious diseases through all phases of transplant care. 

PMID- 25870144
TI  - Influence of sexual dimorphism on pulmonary inflammatory response in adult mice
      exposed to chloroform.
AB  - Chloroform is an organic solvent used as an intermediate in the synthesis of
      various fluorocarbons. Despite its widespread use in industry and agriculture,
      exposure to chloroform can cause illnesses such as cancer, especially in the
      liver and kidneys. The aim of the study was to analyze the effects of chloroform
      on redox imbalance and pulmonary inflammatory response in adult C57BL/6 mice.
      Forty animals were divided into 4 groups (N = 10): female (FCG) and male (MCG)
      controls, and females (FEG) and males (MEG) exposed to chloroform (7.0 ppm) 3
      times/d for 20 minutes for 5 days. Total and differential cell counts, oxidative
      damage analysis, and protein carbonyl and antioxidant enzyme catalase (CAT)
      activity measurements were performed. Morphometric analyses included alveolar
      area (Aa) and volume density of alveolar septa (Vv) measurements. Compared to FCG
      and MCG, inflammatory cell influx, oxidative damage to lipids and proteins, and
      CAT activity were higher in FEG and MEG, respectively. Oxidative damage and
      enzyme CAT activity were higher in FEG than in FCG. The Aa was higher in FEG and
      MEG than in FCG and MCG, respectively. The Vv was lower in FEG and MEG than in
      FCG and MCG, respectively. This study highlights the risks of occupational
      chloroform exposure at low concentrations and the intensity of oxidative damage
      related to gender. The results validate a model of acute exposure that provides
      cellular and biochemical data through short-term exposure to chloroform. 

PMID- 25870146
TI  - Mechanistic Rationale to Target PTEN-Deficient Tumor Cells with Inhibitors of the
      DNA Damage Response Kinase ATM.
AB  - Ataxia telangiectasia mutated (ATM) is an important signaling molecule in the DNA
      damage response (DDR). ATM loss of function can produce a synthetic lethal
      phenotype in combination with tumor-associated mutations in FA/BRCA pathway
      components. In this study, we took an siRNA screening strategy to identify other
      tumor suppressors that, when inhibited, similarly sensitized cells to ATM
      inhibition. In this manner, we determined that PTEN and ATM were synthetically
      lethal when jointly inhibited. PTEN-deficient cells exhibited elevated levels of
      reactive oxygen species, increased endogenous DNA damage, and constitutive ATM
      activation. ATM inhibition caused catastrophic DNA damage, mitotic cell cycle
      arrest, and apoptosis specifically in PTEN-deficient cells in comparison with
      wild-type cells. Antioxidants abrogated the increase in DNA damage and ATM
      activation in PTEN-deficient cells, suggesting a requirement for oxidative DNA
      damage in the mechanism of cell death. Lastly, the ATM inhibitor KU-60019 was
      specifically toxic to PTEN mutant cancer cells in tumor xenografts and reversible
      by reintroduction of wild-type PTEN. Together, our results offer a mechanistic
      rationale for clinical evaluation of ATM inhibitors in PTEN-deficient tumors.

PMID- 25870145
TI  - Acquired Resistance to the Mutant-Selective EGFR Inhibitor AZD9291 Is Associated
      with Increased Dependence on RAS Signaling in Preclinical Models.
AB  - Resistance to targeted EGFR inhibitors is likely to develop in EGFR-mutant lung
      cancers. Early identification of innate or acquired resistance mechanisms to
      these agents is essential to direct development of future therapies. We describe
      the detection of heterogeneous mechanisms of resistance within populations of
      EGFR-mutant cells (PC9 and/or NCI-H1975) with acquired resistance to current and
      newly developed EGFR tyrosine kinase inhibitors, including AZD9291. We report the
      detection of NRAS mutations, including a novel E63K mutation, and a gain of copy
      number of WT NRAS or WT KRAS in cell populations resistant to gefitinib,
      afatinib, WZ4002, or AZD9291. Compared with parental cells, a number of resistant
      cell populations were more sensitive to inhibition by the MEK inhibitor
      selumetinib (AZD6244; ARRY-142886) when treated in combination with the
      originating EGFR inhibitor. In vitro, a combination of AZD9291 with selumetinib
      prevented emergence of resistance in PC9 cells and delayed resistance in NCI
      H1975 cells. In vivo, concomitant dosing of AZD9291 with selumetinib caused
      regression of AZD9291-resistant tumors in an EGFRm/T790M transgenic model. Our
      data support the use of a combination of AZD9291 with a MEK inhibitor to delay or
      prevent resistance to AZD9291 in EGFRm and/or EGFRm/T790M tumors. Furthermore,
      these findings suggest that NRAS modifications in tumor samples from patients who
      have progressed on current or EGFR inhibitors in development may support
      subsequent treatment with a combination of EGFR and MEK inhibition.

PMID- 25870147
TI  - Eu(III) luminescence and tryptophan fluorescence spectroscopy as a tool for
      understanding interactions between hen egg white lysozyme and metal-substituted
      Keggin type polyoxometalates.
AB  - The interaction between the lacunary Keggin K7PW11O39, the Eu(III)-substituted
      Keggin K4EuPW11O39 (Eu-Keggin) and the Ce(IV)-substituted Keggin
      [Me2NH2]10[Ce(PW11O39)2] (Ce-Keggin) polyoxometalates (POMs), and the proteins
      hen egg white lysozyme (HEWL) and the structurally homologous alpha-lactalbumin
      (alpha-LA) was studied by steady state and time-resolved Eu(III) luminescence and
      tryptophan (Trp) fluorescence spectroscopy. The excitation spectrum of Eu-Keggin
      at lower concentrations ([Eu-Keggin]<100 MUM) is dominated by a ligand-to-metal
      charge transfer band (291 nm). For higher concentrations ([Eu-Keggin]>250 MUM)
      the (5)L6<-(7)F0 transition becomes the most intense peak. In the absence of
      protein, the number of coordinated water molecules to the Eu(III) centre of Eu
      Keggin is 4, indicating a 1:1 Eu(III):POM species. In the presence of phosphate
      buffer this number linearly decreases from 4 to 2 upon increasing phosphate
      buffer concentration. Upon addition of HEWL, there are no coordinated water
      molecules, suggesting interaction between Eu-Keggin and the protein surface. In
      addition, this interaction results in a more than threefold increase of the
      hypersensitive (5)D0->(7)F2 transition for the Eu-Keggin/HEWL mixture. The
      calculated association constant amounted to 2.2*10(2) M(-1) for the Eu
      Keggin/HEWL complex. Tryptophan fluorescence quenching studies were performed and
      the quenching constants were calculated to be 9.1*10(4) M(-1), 4*10(4) M(-1) and
      4.1*10(5) M(-1) for the lacunary Keggin/HEWL, the Eu-Keggin/HEWL and the Ce
      Keggin/HEWL complexes, respectively. The number of bound POM molecules to HEWL
      was 1.04 for the lacunary Keggin POM, and 1.0 for Eu-Keggin, indicating the
      formation of a 1:1 POM/HEWL complex. The value of 1.38 for Ce-Keggin might
      indicate a transition from 1:1 to 1:2 interaction.

PMID- 25870148
TI  - Influence of Language of Administration on ImPACT Performance by Bilingual
      Spanish-English College Students.
AB  - Previous research has suggested that there are performance differences on the
      Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) battery
      related to language of administration, such that scores are higher with the
      English than the Spanish version of the battery. This study extended those
      findings in a within-subjects design, evaluating neurocognitive performance of 58
      bilingual English-Spanish-speaking individuals who completed ImPACT in both
      languages. Results revealed a significant multivariate effect of language of test
      administration, p < .01; partial eta(2) = 0.23, with significantly better English
      language performance on Verbal Memory and Visual Motor Speed composite scores,
      but not Visual Memory, Reaction Time, or Total Symptom score. Results are
      discussed in relation to potential linguistic biases of the ImPACT and functional
      language dominance that may contribute to the lower scores. These results extend
      previous findings and suggest a need for separate normative data for Spanish
      speaking individuals completing the ImPACT battery if baseline data are not
      present. 

PMID- 25870149
TI  - TRICHOME AND ARTEMISININ REGULATOR 1 Is Required for Trichome Development and
      Artemisinin Biosynthesis in Artemisia annua.
AB  - Trichomes, small protrusions on the surface of many plant species, can produce
      and store various secondary metabolic products. Artemisinin, the most famous and
      potent medicine for malaria, is synthesized, stored, and secreted by Artemisia
      annua trichomes. However, the molecular basis regulating the biosynthesis of
      artemisinin and the development of trichomes in A. annua remains poorly
      understood. Here, we report that an AP2 transcription factor, TRICHOME AND
      ARTEMISININ REGULATOR 1 (TAR1), plays crucial roles in regulating the development
      of trichomes and the biosynthesis of artemisinin in A. annua. TAR1, which encodes
      a protein specially located in the nucleus, is mainly expressed in young leaves,
      flower buds, and some trichomes. In TAR1-RNAi lines, the morphology of trichomes
      and the composition of cuticular wax were altered, and the artemisinin content
      was dramatically reduced, which could be significantly increased by TAR1
      oeverexpression. Expression levels of several key genes that are involved in
      artemisinin biosynthesis were altered when TAR1 was silenced or overexpressed. By
      the electrophoretic mobility shift, yeast one-hybrid and transient transformation
      beta-glucuronidase assays, we showed that ADS and CYP71AV1, two key genes in the
      biosynthesis pathway of artemisinin, are likely the direct targets of TAR1. Taken
      together, our results indicate that TAR1 is a key component of the molecular
      network regulating trichome development and artemisinin biosynthesis in A. annua.

PMID- 25870150
TI  - Bare metal stents: I am still standing.

PMID- 25870151
TI  - Rational use of rotational atherectomy in calcified lesions in the drug-eluting
      stent era: Review of the evidence and current practice.
AB  - Percutaneous coronary interventions of calcified coronary lesions are associated
      with worse clinical outcomes compared with noncalcified lesions and are still
      considered a technical challenge for interventional cardiologists. Rotational
      atherectomy (RA) can effectively optimize lesion preparation through plaque
      modification of heavily calcified coronary lesions. However, in conventional
      balloon angioplasty and bare metal stent eras, the use of RA was not associated
      with a significant improvement in restenosis and target lesion revascularization
      in patients with calcified lesions. Drug-eluting stents (DES) dramatically
      reduced the rates of restenosis and major adverse cardiac events. In the DES era,
      the need for RA is therefore questionable. Recently, some studies have reported
      clinical outcomes of patients with calcified lesions treated with DES and RA. In
      this article, we aim to critically review results from these randomized and
      observational clinical studies assessing the use of RA in the DES era.

PMID- 25870152
TI  - Safety and efficacy of limus-eluting stents and balloon angioplasty for sirolimus
      eluting in-stent restenosis.
AB  - OBJECTIVES: The aim of this study was to compare the safety and efficacy of
      everolimus-eluting stent (EES), sirolimus-eluting stent (SES), and plain old
      balloon angioplasty (POBA) for the treatment of SES in-stent restenosis (S-ISR).
      BACKGROUND: The optimal treatment for drug-eluting in-stent restenosis remains
      controversial. METHODS: The study cohort comprised 310 consecutive patients (444
      lesions) who presented with S-ISR to our institution and underwent treatment with
      EES (43 patients), SES (102), or POBA (165). The analyzed clinical parameters
      were the 1-year rates of death, Q-wave myocardial infarction (MI), target lesion
      revascularization (TLR), target vessel revascularization (TVR), definite stent
      thrombosis (ST) and major adverse cardiac event (MACE) defined as the composite
      of death, MI, or TLR at 1-year. RESULTS: The three groups were well matched for
      the conventional risk factors for coronary artery disease except for smoking. The
      1-year analyzed clinical parameters were similar in the three groups: MACE
      (EES=14%, SES=18%, POBA=20%; p=0.65), death (EES=2.3%, SES=6.2%, POBA=6.1%;
      p=0.61), MI (EES=4.8%, SES=2.1%, POBA=2.5%; p=0.69), TLR (EES=11.9%, SES=12.1%,
      POBA=24%; p=0.78), and TVR (EES=11.9%, SES=24.8%, POBA=22.2%; p=0.23). There were
      no cases of definite ST. MACE-free rate was significantly lower in patients with
      recurrent in-stent restenosis (log-rank p=0.006). Presentation with acute MI,
      number of treated lesions and a previous history of MI were found to be
      independent predictors of MACE. CONCLUSIONS: In patients presenting with S-ISR,
      treatment with implantation of an EES, SES, or POBA is associated with similar
      clinical outcomes. Patients presenting with recurrent ISR may have a poorer
      clinical outcome.

PMID- 25870153
TI  - In vitro assessment of physiological impact of recipient artery intervention on
      the contralateral donor artery.
AB  - BACKGROUND: Donor artery fractional flow reserve (FFR) often improves after
      treatment of recipient artery stenosis, but the physiological mechanism
      underlying this phenomenon has not been elucidated. This study aimed to assess
      two novel equations that explain the donor-recipient artery interaction. METHOD:
      Eq. (A) predicts the donor artery FFR after complete release of recipient artery
      stenosis, while Eq. (B) predicts the donor artery FFR after partial release of
      recipient artery stenosis. Eq. (B) is a general form of Eq. (A). FFR'1-pred =
      ((FFR1-CFI1)(FFR2-CFI2)-CFI1CFI2(1-FFR1)(1-FFR2)+CFI1(1-FFR1)(1-CFI2))/((1-C
      FI1)(FFR2-CFI2)) (A) FFR''1-pred = ((FFR1-CFI1)(FFR2-CFI2)-CFI1CFI2(1-FFR1)(1
      FFR2)+CFI1(1-FFR1)(1-CFI2))FFR'2/((1-C FI1)(FFR2-CFI2)) (B) Eqs. (A) and (B) were
      assessed using an in vitro model of coronary circulation with a collateral
      channel connecting the donor and recipient arteries. RESULTS: The donor artery
      FFR always improved after releasing the recipient artery stenosis. A good linear
      correlation was found between the predicted FFR of Eq. (A) and the actual FFR
      (n=40, r=0.95, p<0.0001) and between the predicted FFR of Eq. (B) and the actual
      FFR (n=40, r=0.94, p<0.0001). CONCLUSIONS: Eqs. (A) and (B) accurately predicted
      the true FFR value of the donor artery in a coronary circulation model and
      explain the donor-recipient artery interaction observed in clinical practice.

PMID- 25870154
TI  - Prenatal reflective functioning in primiparous women with a high-risk profile.
AB  - The concept of maternal reflective functioning (RF) has been gaining increasing
      interest as a possible intermediate mechanism in associations between a wide
      range of psychosocial risk factors and poor child outcomes. The purpose of the
      present study was to determine which psychosocial risk factors are linked to
      prenatal RF in a high-risk (HR) group of primiparous women. Differences in
      prenatal RF between the HR group and a low-risk (LR) control group also were
      examined. The sample consisted of 162 women (M = 22.22 years, SD = 2.39; 83
      classified as HR). RF was coded from the Pregnancy Interview (A. Slade, 2007a).
      Risk status was assessed by means of the Mini-International Neuropsychiatric
      Interview-plus (M.I.N.I.-plus; D.V. Sheehan et al., 1997) and several
      questionnaires. HR women demonstrated significantly lower RF quality than did the
      LR group. Regression analyses indicated that maternal education, size of social
      support network, and substance use during pregnancy were the strongest predictors
      of prenatal RF for the HR group. The results suggest that maternal RF potentially
      could be an important target for those prevention and intervention programs that
      aim to reduce adverse psychosocial development in offspring of HR mothers. 

PMID- 25870155
TI  - Prognosis in advanced lung cancer--A prospective study examining key
      clinicopathological factors.
AB  - OBJECTIVES: In patients with advanced incurable lung cancer deciding as to the
      most appropriate treatment (e.g., chemotherapy or supportive care only) is
      challenging. In such patients the TNM classification system has reached its
      ceiling therefore other factors are used to assess prognosis and as such, guide
      treatment. Performance status (PS), weight loss and inflammatory biomarkers
      (Glasgow Prognostic Score (mGPS)) predict survival in advanced lung cancer
      however these have not been compared. This study compares key prognostic factors
      in advanced lung cancer. MATERIALS AND METHODS: Patients with newly diagnosed
      advanced lung cancer were recruited and demographics, weight loss, other
      prognostic factors (mGPS, PS) were collected. Kaplan-Meier and Cox regression
      methods were used to compare these prognostic factors. RESULTS: 390 patients with
      advanced incurable lung cancer were recruited; 341 were male, median age was 66
      years (IQR 59-73) and patients had stage IV non-small cell (n=288) (73.8%) or
      extensive stage small cell lung cancer (n=102) (26.2%). The median survival was
      7.8 months. On multivariate analysis only performance status (HR 1.74 CI 1.50
      2.02) and mGPS (HR 1.67, CI 1.40-2.00) predicted survival (p<0.001). Survival at
      3 months ranged from 99% (ECOG 0-1) to 74% (ECOG 2) and using mGPS, from 99%
      (mGPS0) to 71% (mGPS2). In combination, survival ranged from 99% (mGPS 0, ECOG 0
      1) to 33% (mGPS2, ECOG 3). CONCLUSION: Performance status and the mGPS are
      superior prognostic factors in advanced lung cancer. In combination, these
      improved survival prediction compared with either alone.

PMID- 25870156
TI  - Predictive role of erythrocyte macrocytosis during treatment with pemetrexed in
      advanced non-small cell lung cancer patients.
AB  - OBJECTIVES: Pemetrexed has been approved for the treatment of advanced non-small
      cell lung cancer (NSCLC) non-squamous histology, both as first- and second-line
      therapy. Pemetrexed is an antimetabolite drug, that inhibits enzymes involved in
      nucleotides bio-synthesis arresting cancer cells cycle. The aim of this study was
      the evaluation of the impact of pemetrexed on erythrocyte mean corpuscular volume
      (MCV) change and its possible correlation with disease control rate (DCR),
      progression free (PFS) and overall survival (OS) in NSCLC patients. MATERIALS AND
      METHODS: A retrospective collection of clinical and laboratory data (including
      basal MCV and maximum MCV occurred during therapy) in advanced NSCLC patients
      treated with pemetrexed at seven Italian centers was performed. Nonparametric
      tests, univariate and multivariate analysis were used to assess correlation
      between variables and to identify predictors of outcomes. RESULTS: 191 patients
      were enrolled: median age 62, 60% male, 61% performance status (PS) 0, 91% stage
      IV, 88% adenocarcinoma histotype, 25% never smoker, 62% received pemetrexed as
      first-line. Mean MCV significantly increased from basal (89fL) to during
      treatment (94fL), with mean DeltaMCV=4fL. The median time from therapy start to
      maximum MCV was 2.2 months. Median PFS was 7 [CI95% 6-8] and 3 [CI95% 2-4] months
      [P=0.0016], and median survival was 17 [CI95% 12-23] and 10 [CI95% 8-12] months
      [P=0.02], in patients with DeltaMCV>5fL (n=80) and DeltaMCV<=5fL (n=111),
      respectively. Multivariate analysis identified age >=62, PS 0, adenocarcinoma
      histology and DeltaMCV>5fL as independent predictors of longer PFS. A
      DeltaMCV>5fL significantly correlates with DCR. CONCLUSION: Pemetrexed induces
      macrocytosis. DeltaMCV>5fL on pemetrexed therapy correlated with better DCR, PFS
      and OS. These results deserve further validation in prospective studies.

PMID- 25870157
TI  - So! What's aging? Is cardiovascular aging a disease?
AB  - "Inside every old person is a young person wondering what happened." So, what is
      aging? Aging is a manifestation of progressive, time-dependent failure of
      molecular mechanisms that create disorder within a system of DNA and its
      environment (nuclear, cytosolic, tissue, organ, organism, other organisms,
      society, terra firma, atmosphere, universe). Continuous signaling, transmitted
      with different kinetics across each of these environments, confers a "mutual
      enslavement" that creates ordered functions among the components within the
      system. Accrual of this molecular disorder over time, i.e. during aging, causes
      progressive changes in the structure and function of the heart and arteries that
      are quite similar in humans, non-human primates, rabbits and rats that compromise
      cardiovascular reserve function, and confer a marked risk for incident
      cardiovascular disease. Nearly all aspects of signaling within the DNA
      environment system within the heart and arteries become disordered with advancing
      age: Signals change, as does sensing of the signals, transmission of signals and
      responses to signals, impaired cell renewal, changes in the proteome due to
      alterations in genomic transcription, mRNA translation, and proteostasis. The
      density of some molecules becomes reduced, and post-translational modifications,
      e.g. oxidation and nitration phosphorylation, lead to altered misfolding and
      disordered molecular interactions. The stoichiometry and kinetics of enzymatic
      and those reactions which underlie crucial cardiac and vascular cell functions
      and robust reserve mechanisms that remove damaged organelles and proteins
      deteriorate. The CV cells generate an inflammatory defense in an attempt to limit
      the molecular disorder. The resultant proinflammatory milieu is not executed by
      "professional" inflammatory cells (i.e. white blood cells), however, but by
      activation of renin-angiotensin-aldosterone endothelin signaling cascades that
      leads to endothelial and vascular smooth muscle and cardiac cells' phenotype
      shifts, resulting in production of inflammatory cytokines. Progressive molecular
      disorder within the heart and arteries over time leads to an excessive allostatic
      load on the CV system, that results in an increase and "overshoot" in the
      inflammatory defense signaling. This age-associated molecular disorder-induced
      inflammation that accrues in the heart and arteries does not, itself, cause
      clinical signs or symptoms of CVD. Clinical signs and symptoms of these CVDs
      begin to emerge, however, when the age-associated inflammation in the heart and
      arteries exceeds a threshold. Thus, an emerging school of thought is that
      accelerated age-associated alterations within the heart and arteries, per se,
      ought to be considered to be a type of CVD, because the molecular disorder and
      the inflammatory milieu it creates within the heart and arteries with advancing
      age are the roots of the pathophysiology of most cardiovascular diseases, e.g.
      athersclerosis and hypertension. Because many effects of aging on the CV system
      can be delayed or attenuated by changes in lifestyle, e.g. diet and exercise, or
      by presently available drugs, e.g. those that suppress Ang II signaling, CV aging
      is a promising frontier in preventive cardiology that is not only ripe for, but
      also in dire need of attention! There is an urgency to incorporate the concept of
      cardiovascular aging as a disease into clinical medicine. But, sadly, the reality
      of the age-associated molecular disorder within the heart and ateries has, for
      the most part, been kept outside of mainstream clinical medicine. This article is
      part of a Special Issue entitled CV Aging. 

PMID- 25870158
TI  - Resolvin D1 activates the inflammation resolving response at splenic and
      ventricular site following myocardial infarction leading to improved ventricular
      function.
AB  - Unresolved inflammation is a major contributor to the development of heart
      failure following myocardial infarction (MI). Pro-resolving lipid mediators, such
      as resolvins (e.g. RvD1), are biosynthesized endogenously. The role of RvD1 in
      resolving post-MI inflammation has not been elucidated due to its unstable
      nature. Here, we have tested the role for two forms of RvD1, after incorporation
      into liposomes (Lipo-RvD1) and its free acid form (RvD1) in the left ventricle
      (LV) and splenic remodeling post-MI. 8 to 12-week old male, C57BL/6J-mice were
      subjected to coronary artery ligation and Lipo-RvD1 or RvD1 (3 MUg/kg/day) was
      injected 3h post-MI for day (d)1 or until d5. No-MI mice and saline-injected MI
      mice served as controls. RvD1 injected groups showed improved fractional
      shortening post-MI; preserving transient changes in the splenic reservoir
      compared to MI-saline. RvD1-groups showed an early exit of neutrophils from LV
      and spleen at d5 post-MI with an increased expression of lipoxin A4 receptor
      (ALX; synonym formyl peptide receptor; FPR2) compared to the MI-saline group. The
      levels of pro-resolving mediators RvD1, RvD2, Maresin 1 (MaR1) and Lipoxin A4
      (LXA4) were increased in spleens from RvD1 injected mice at d5 post-MI. RvD1
      administration reduced macrophage density, ccr5 and cxcl5 levels at d5 post-MI
      compared to saline injected mice (both, p < 0.05). Increased transcripts of mrc
      1, arg-1 and Ym-1 (all, p < 0.05) suggest macrophage-mediated clearance of
      necrotic cells in RvD1-groups. RvD1 reduced the pro-fibrotic genes (colla1,
      coll2a1 and tnc (all; p < 0.05)) and decreased collagen deposition, thereby
      reducing post-MI fibrosis and thus stabilizing the extracellular matrix. In
      summary, RvD1 and Lipo-RvD1 promote the resolution of acute inflammation
      initiated by MI, thereby delaying the onset of heart failure.

PMID- 25870160
TI  - Do bimanual coordination, tool use, and body posture contribute equally to hand
      preferences in bonobos?
AB  - Approximately 90% of the human population is right-handed. The emergence of this
      hand preference in humans is thought to be linked to the ability to execute
      complex tasks and habitual bipedalism. In order to test these hypotheses, the
      present study explored, for the first time, hand preference in relation to both
      body posture (seated and bipedal) and task complexity (bimanual coordination and
      two tool use tasks of different complexity) in bonobos (Pan paniscus). Few
      studies have explored the effects of both posture and task complexity on
      handedness, and investigations with bonobos are scarce, particularly studies on
      tool use. Our study aims to overcome such a gap by addressing two main questions:
      1) Does a bipedal posture increase the strength of hand preference and/or create
      a directional bias to the use of the right hand? 2) Independent of body posture,
      does task complexity increase the strength of the hand preference and/or create a
      directional bias to the use of the right hand? Our results show that independent
      of body posture, the more complex the task, the more lateralization occurred.
      Moreover, subjects tended to be right-handed for tasks involving tool use.
      However, posture had no significant effect on hand preference in the tasks tested
      here. Therefore, for a given task, bonobos were not more lateralized in a bipedal
      posture than in a seated one. Task complexity might thus have contributed more
      than bipedal posture to the emergence of human lateralization and the
      preponderance of right-handedness, although a larger sample size and more data
      are needed to be conclusive. 

PMID- 25870161
TI  - Vitamin K antagonist-experienced patients with a history of stroke/transient
      ischaemic attack who switched from warfarin to dabigatran increased their rate of
      recurrent stroke/transient ischaemic attack compared with those on warfarin.

PMID- 25870162
TI  - An abnormally slow proton transfer reaction in a simple HBO derivative due to
      ultrafast intramolecular-charge transfer events.
AB  - We report on the steady-state, picosecond and femtosecond time-resolved studies
      of a charge and proton transfer dye 6-amino-2-(2'-hydroxyphenyl)benzoxazole (6A
      HBO) and its methylated derivative 6-amino-2-(2'-methoxyphenyl)benzoxazole (6A
      MBO), in different solvents. With femtosecond resolution and comparison with the
      photobehaviour of 6A-MBO, we demonstrate for 6A-HBO in solution, the
      photoproduction of an intramolecular charge-transfer (ICT) process at S1 taking
      place in ~140 fs or shorter, followed by solvent relaxation in the charge
      transferred species. The generated structure (syn-enol charge transfer conformer)
      experiences an excited-state intramolecular proton-transfer (ESIPT) reaction to
      produce a keto-type tautomer. This subsequent proton motion occurs in 1.2 ps (n
      heptane), 14 ps (DCM) and 35 ps (MeOH). In MeOH, it is assisted by the solvent
      molecules and occurs through tunneling for which we got a large kinetic isotope
      effect (KIE) of about 13. For the 6A-DBO (deuterated sample in CD3OD) the global
      proton-transfer reaction takes place in 200 ps, showing a remarkable slow KIE
      regime. The slow ESIPT reaction in DCM (14 ps), not through tunnelling as it is
      not sensitive to OH/OD exchange, has however to overcome an energy barrier using
      intramolecular as well as solvent coordinates. The rich ESIPT dynamics of 6A-HBO
      in the used solutions is governed by an ICT reaction, triggered by the amino
      group, and it is solvent dependent. Thus, the charge injection to a 6A-HBO
      molecular frame makes the ICT species more stable, and the phenol group less
      acidic, slowing down the subsequent ESIPT reaction. Our findings bring new
      insights into the coupling between ICT and ESIPT reactions on the potential
      energy surfaces of several barriers. 

PMID- 25870159
TI  - Genome-wide association studies of late-onset cardiovascular disease.
AB  - Human genetics is a powerful tool for discovering causal mediators of human
      disease and physiology. Cardiovascular diseases with late onset in the lifecourse
      have historically not been considered genetic diseases, but in recent years the
      contribution of a heritable factor has been established. More importantly, over
      the last decade genome-wide association studies (GWASs) have identified many loci
      associated with late-onset cardiovascular diseases including coronary artery
      disease, carotid artery disease, ischemic stroke, aortic aneurysm, peripheral
      vascular disease, atrial fibrillation, valvular disease and correlates of
      vascular and myocardial function. Here we review findings from GWASs considered
      statistically robust with regard to multiple testing (p<5*10(-8)) for late-onset
      cardiovascular diseases and traits. Although for only a handful of the 92 genetic
      loci described here have the mechanisms underlying disease association been
      established, new and previously unsuspected pathways have been implicated for
      several conditions. Examples include a role for NO signaling in myocardial
      repolarization and sudden cardiac death and a role for the protein sortilin in
      lipid metabolism and coronary artery disease. Genetic loci with multiple trait
      associations have also provided novel biological insights. For example, of the 46
      genetic loci associated with coronary artery disease, only 16 are also associated
      with conventional risk factors for cardiovascular disease whereas the remaining
      two thirds may reflect novel pathways. Much work remains to functionally
      characterize genetic loci and for clinical utility, but accruing insights into
      the biological basis of cardiovascular aging in human populations promise to
      point to novel therapeutic and preventive strategies. This article is part of a
      Special Issue entitled 'SI:CV Aging'. 

PMID- 25870163
TI  - Trends and social differentials in child mortality in Rwanda 1990-2010: results
      from three demographic and health surveys.
AB  - BACKGROUND: Rwanda has embarked on ambitious programmes to provide equitable
      health services and reduce mortality in childhood. Evidence from other countries
      indicates that advances in child survival often have come at the expense of
      increasing inequity. Our aims were to analyse trends and social differentials in
      mortality before the age of 5 years in Rwanda from 1990 to 2010. METHODS: We
      performed secondary analyses of data from three Demographic and Health Surveys
      conducted in 2000, 2005 and 2010 in Rwanda. These surveys included 34 790
      children born between 1990 and 2010 to women aged 15-49 years. The main outcome
      measures were neonatal mortality rates (NMR) and under-5 mortality rates (U5MR)
      over time, and in relation to mother's educational level, urban or rural
      residence and household wealth. Generalised linear mixed effects models and a
      mixed effects Cox model (frailty model) were used, with adjustments for
      confounders and cluster sampling method. RESULTS: Mortality rates in Rwanda
      peaked in 1994 at the time of the genocide (NMR 60/1000 live births, 95% CI 51 to
      65; U5MR 238/1000 live births, 95% CI 226 to 251). The 1990s and the first half
      of the 2000s were characterised by a marked rural/urban divide and inequity in
      child survival between maternal groups with different levels of education.
      Towards the end of the study period (2005-2010) NMR had been reduced to 26/1000
      (95% CI 23 to 29) and U5MR to 65/1000 (95% CI 61 to 70), with little or no
      difference between urban and rural areas, and household wealth groups, while
      children of women with no education still had significantly higher U5MR.
      CONCLUSIONS: Recent reductions in child mortality in Rwanda have concurred with
      improved social equity in child survival. Current challenges include the
      prevention of newborn deaths.

PMID- 25870165
TI  - Shifting the patient education paradigm.

PMID- 25870164
TI  - High hepatitis C virus prevalence and incidence in a community cohort of young
      heroin injectors in a context of extensive harm reduction programmes.
AB  - BACKGROUND: Cohort studies on hepatitis C virus (HCV) among drug injectors are
      scarcer than studies on HIV. Combined harm reduction interventions (HRIs) can
      prevent HCV infection. Spain has a medium-high coverage of HRIs. METHODS: 513
      young heroin users who injected drugs in the past 12 months (recent injectors)
      were street-recruited in 2001-2003 and followed until 2006 in three Spanish
      cities; 137 were anti-HCV seronegative, 77 of whom had >=1 follow-up visit. Dried
      blood spots were tested for anti-HCV. HCV incidence and predictors of infection
      were estimated using Poisson models. RESULTS: At baseline, 73% were anti-HCV
      positive. Overall incidence (n=77) of HCV seroconversion was 39.8/100 person
      years (py) (95% CI 28.7 to 53.8). Excluding non-injectors during follow-up from
      the analysis (n=57), HCV incidence was 52.9/100 py (95% CI 37.4 to 72.5).
      Injecting at least weekly (incidence rate ratio (IRR)=5.2 (95% CI 2.5 to 11.1))
      and having >=2 sexual partners (IRR=2.2 (95% CI 1.1 to 4.7)) were independent
      predictors of HCV seroconversion; drug-injection history <2 years was marginally
      associated (IRR=2.4 (95% CI 0.9 to 4.7)). HCV incidence may have been
      underestimated due to differential attrition. CONCLUSIONS: Despite fairly high
      HRI coverage among Spanish drug injectors, a distressingly high incidence of HCV
      in a context of high HCV prevalence was found among young heroin injectors.

PMID- 25870166
TI  - The iNOS/Src/FAK axis contributes to lithium chloride-mediated macrophage
      migration.
AB  - Lithium chloride (LiCl) has long been used as a mood stabilizer for bipolar mood
      depression patients. However, its biological effects on immune cells are unclear
      yet. In this study, we observed that upon LiCl stimulation, the motility and the
      content of total protein tyrosine phosphorylation in RAW264.7 macrophages and
      murine peritoneal macrophages (PEMs) were significantly increased. The inhibition
      of LiCl-induced macrophage migration by PP2 (an inhibitor for Src family kinases
      (SFKs)) suggested the involvement of SFKs in this process. Interestingly, LiCl
      induced NF-kB activation, and while Src was greatly induced, the expression of
      its myeloid relatives (i.e. Lyn, Fgr, Hck) was almost unaltered in RAW264.7
      cells. Knockdown of Src suppressed LiCl-elicited movement and the level of FAK Pi
      Tyr861, which could be reversed by siRNA-resistant Src. Consistent with Src and
      migration increment was iNOS-dependent in macrophages, markedly reduced Src
      expression, activity and cell migration were observed in iNOS-null PEMs treated
      with LiCl. Moreover, FAK knockdown suppressed LiCl-stimulated macrophage
      motility, suggesting the involvement of FAK in this process. Remarkably, similar
      increment of iNOS, Src, FAK Pi-Tyr861 and migration ability could also be
      detected in RAW264.7 treated with other GSK3beta inhibitors (i.e. SB216763 and
      Kenpaullone). These results corroborate that through inhibition of GSK3beta, the
      iNOS/Src/FAK axis occupies a critical role in macrophage locomotion in response
      to LiCl. 

PMID- 25870167
TI  - Two-stage revision of prosthetic hip joint infections using antibiotic-loaded
      cement spacers: When is the best time to perform the second stage?
AB  - AIM: Managing periprosthetic joint infections remains a challenging task, and
      adequate treatment strategies seem to be mandatory to avoid irreversible damage
      of the affected joint and/or systemic complications. Two-stage revision
      arthroplasty includes removing all implants and subsequent implantation of an
      antibiotic-loaded cement spacer, followed by revision arthroplasty as the second
      stage. Although this procedure is well described in the literature, results
      remain unpredictable due to various clinical findings and the absence of
      prospective randomised trials. We analysed (1) mortality and (2) reinfection
      rates in a series of patients who underwent two-stage revision surgery for
      periprosthetic hip joint infections with antibiotic-augmented joint spacers. We
      maintained a special focus on the spacer retention period and its influence on
      outcome in order to determine the best time for second-stage surgery. PATIENTS
      AND METHODS: A consecutive series of 76 patients with native and periprosthetic
      hip joint infections and who underwent two-stage revision surgery with antibiotic
      loaded cement spacers were studied between 2005 and 2010. The second-stage
      operation was performed when it was assumed that infection was eradicated. The
      further operative procedure depended upon intra-operative findings (frozen
      section, local status). RESULTS: Mean implant-free period with the antibiotic
      loaded spacer in situ was 12.6 weeks. Spacer re-implantation was necessary in 13
      cases due to positive signs of acute infection in the frozen section and suspect
      intra-operative findings. Eight patients were not operated for a second time in
      the investigated time period due to poor general condition. In 40 patients, the
      spacer retention period was four to 11 weeks: <four weeks for five and >11 weeks
      for 23. We observed a significantly higher proportion of women free from
      reinfection in the four to 11-week group than in patients with the shorter or
      longer period. CONCLUSION: According to our findings, the optimal timing for
      second-stage surgery as a second-stage procedure is between four and 11 weeks. A
      significantly optimal reinfection rate was seen in patients undergoing revision
      arthroplasty within that time frame, and 90% of those patients remained infection
      free until final follow-up.

PMID- 25870168
TI  - Role of a collagen membrane in adhesion prevention strategy for complex spinal
      surgeries.
AB  - PURPOSE: Following lumbar spine surgery, postoperative complications can appear,
      including epidural adhesions. The formation of fibrosis around the dura mater
      can, on the one hand, lead to compression of the nerve roots with recurrent
      radicular pain and, on the other hand, can increase the risks of specific
      complications at spinal re-intervention (haematomas and dural breaches). The aim
      of this prospective monocentric study was to assess the safety of a new collagen
      antiadhesion membrane in vertebral osteotomy surgery where scar tissue and
      adhesions are important. METHODS: Twenty-six patients consecutively operated for
      lumbar posterior subtraction osteotomy with implantation of a collagen-based anti
      adhesion membrane were evaluated. Membrane tolerance was evaluated at the short
      and midterm during the regular follow-up. RESULTS: At six months' follow-up,
      postoperative pain [visual analogue scale (VAS)] and disability (Oswestry
      Disability Index score) were significantly reduced 33.1 and 43.1%, respectively.
      These results were confirmed at 12-months' follow-up, with a decrease in pain of
      39.9% and in disability of 49.3%. Amongst the observed postoperative
      complications was neither spinal fluid leak nor durotomy. Presence of the
      membrane was not related to complications. Two patients required further surgery
      for infection and nonunion at the osteotomised level. Adhesions to the dura mater
      were limited and thin, facilitating exposure. CONCLUSIONS: This study shows good
      tolerance of the collagen based membrane for spinal osteotomy and its
      satisfactory use for preventing postoperative epidural adhesions. Good surgical
      practice associated with an anti-adhesion barrier may decrease fibrosis formation
      and improve postoperative functional results.

PMID- 25870169
TI  - Development of a novel imaging informatics-based system with an intelligent
      workflow engine (IWEIS) to support imaging-based clinical trials.
AB  - Imaging based clinical trials can benefit from a solution to efficiently collect,
      analyze, and distribute multimedia data at various stages within the workflow.
      Currently, the data management needs of these trials are typically addressed with
      custom-built systems. However, software development of the custom-built systems
      for versatile workflows can be resource-consuming. To address these challenges,
      we present a system with a workflow engine for imaging based clinical trials. The
      system enables a project coordinator to build a data collection and management
      system specifically related to study protocol workflow without programming. Web
      Access to DICOM Objects (WADO) module with novel features is integrated to
      further facilitate imaging related study. The system was initially evaluated by
      an imaging based rehabilitation clinical trial. The evaluation shows that the
      cost of the development of system can be much reduced compared to the custom
      built system. By providing a solution to customize a system and automate the
      workflow, the system will save on development time and reduce errors especially
      for imaging clinical trials. 

PMID- 25870170
TI  - Dense nanoparticles exhibit enhanced vascular wall targeting over neutrally
      buoyant nanoparticles in human blood flow.
AB  - For vascular-targeting carrier (VTC) systems to be effective, carriers must be
      able to localize and adhere to the vascular wall at the target site. Research
      suggests that neutrally buoyant nanoparticles are limited by their inability to
      localize to the endothelium, making them sub-optimal as carriers. This study
      examines whether particle density can be exploited to improve the targeting
      (localization and adhesion) efficiency of nanospheres to the vasculature. Silica
      spheres with 500 nm diameter, which have a density roughly twice that of blood,
      exhibit improved adhesion to inflamed endothelium in an in vitro model of human
      vasculature compared to neutrally buoyant polystyrene spheres of the same size.
      Silica spheres also display better near-wall localization in the presence of red
      blood cells than they do in pure buffer, likely resulting in the observed
      improvement in adhesion. Titania spheres (4 times more dense than blood) adhere
      at levels higher than polystyrene, but only in conditions when gravity or
      centrifugal force acts in the direction of adhesion. In light of the wide array
      of materials proposed for use as carrier systems for drug delivery and
      diagnostics, particle density may be a useful tool for improving the targeting of
      diseased tissues.

PMID- 25870171
TI  - Injectability of calcium phosphate pastes: Effects of particle size and state of
      aggregation of beta-tricalcium phosphate powders.
AB  - The present study discloses a systematic study about the influence of some
      relevant experimental variables on injectability of calcium phosphate cements.
      Non-reactive and reactive pastes were prepared, based on tricalcium phosphate
      doped with 5 mol% (Sr-TCP) that was synthesised by co-precipitation. The varied
      experimental parameters included: (i) the heat treatment temperature within the
      range of 800-1100 degrees C; (ii) different milling extents of calcined powders;
      (iii) the liquid-to-powder ratio (LPR); (iv) the use of powder blends with
      different particle sizes (PS) and particle size distributions (PSD); (v) the
      partial replacement of fine powders by large spherical dense granules prepared
      via freeze granulation method to simulate coarse individual particles. The aim
      was contributing to better understanding of the effects of PS, PSD, morphology
      and state of aggregation of the starting powders on injectability of pastes
      produced thereof. Powders heat treated at 800 and 1000 degrees C with different
      morphologies but with similar apparent PSD curves obtained by milling/blending
      originated completely injectable reactive cement pastes at low LPR. This
      contrasted with non-reactive systems prepared thereof under the same conditions.
      Hypotheses were put forward to explain why the injectability results collected
      upon extruding non-reactive pastes cannot be directly transposed to reactive
      systems. The results obtained underline the interdependent roles of the different
      powder features and ionic strength in the liquid media on determining the flow
      and injectability behaviours.

PMID- 25870174
TI  - The wish to hasten death: Reflections from practice and research.

PMID- 25870175
TI  - Somali asylum seekers' perceptions of privacy in healthcare.
AB  - BACKGROUND: Privacy has been recognized as a basic human right and a part of
      quality of care. However, little is known about the privacy of Somali asylum
      seekers in healthcare, even though they are one of the largest asylum seeker
      groups in the world. OBJECTIVES: The aim of the study was to describe the content
      and importance of privacy and its importance in healthcare from the perspective
      of Somali asylum seekers. RESEARCH DESIGN: The data of this explorative
      qualitative study were collected by four focus group interviews with 18 Somali
      asylum seekers with the help of an interpreter. The data were analysed by
      inductive content analysis. ETHICAL CONSIDERATIONS: Research permissions were
      obtained from the director of the reception centre and from the Department of
      Social Services. Ethical approval was obtained from the Ethics Committee of Turku
      University. FINDINGS: The content of privacy includes visual privacy, physical
      privacy and informational privacy. All contents can be shared with healthcare
      professionals. The importance of privacy includes respect, dignity and freedom.
      DISCUSSION: Privacy is strongly connected to the collectivism of Somali culture
      and religion. Unlike the Western cultures, privacy is not important only for the
      individual; most of all, it is seen to support collectivism. CONCLUSION: Even
      though all contents of privacy can be shared with healthcare professionals, it is
      important to recognize the cultural aspect of privacy especially when using
      interpreters with Somali background.

PMID- 25870172
TI  - Molecular differences in transition zone and peripheral zone prostate tumors.
AB  - Prostate tumors arise primarily in the peripheral zone (PZ) of the prostate, but
      20-30% arise in the transition zone (TZ). Zone of origin may have prognostic
      value or reflect distinct molecular subtypes; however, it can be difficult to
      determine in practice. Using whole-genome gene expression, we built a signature
      of zone using normal tissue from five individuals and found that it successfully
      classified nine tumors of known zone. Hypothesizing that this signature captures
      tumor zone of origin, we assessed its relationship with clinical factors among
      369 tumors of unknown zone from radical prostatectomies (RPs) and found that
      tumors that molecularly resembled TZ tumors showed lower mortality (P = 0.09)
      that was explained by lower Gleason scores (P = 0.009). We further applied the
      signature to an earlier study of 88 RP and 333 transurethral resection of the
      prostate (TURP) tumor samples, also of unknown zone, with gene expression on
      ~6000 genes. We had observed previously substantial expression differences
      between RP and TURP specimens, and hypothesized that this might be because RPs
      capture primarily PZ tumors, whereas TURPs capture more TZ tumors. Our signature
      distinguished these two groups, with an area under the receiver operating
      characteristic curve of 87% (P < 0.0001). Our findings that zonal differences in
      normal tissue persist in tumor tissue and that these differences are associated
      with Gleason score and sample type suggest that subtypes potentially resulting
      from different etiologic pathways might arise in these zones. Zone of origin may
      be important to consider in prostate tumor biomarker research. 

PMID- 25870176
TI  - Ethical issues experienced by healthcare workers in nursing homes: Literature
      review.
AB  - BACKGROUND: Ethical issues are increasingly being reported by care-providers;
      however, little is known about the nature of these issues within the nursing
      home. Ethical issues are unavoidable in healthcare and can result in
      opportunities for improving work and care conditions; however, they are also
      associated with detrimental outcomes including staff burnout and moral distress.
      OBJECTIVES: The purpose of this review was to identify prior research which
      focuses on ethical issues in the nursing home and to explore staffs' experiences
      of ethical issues. METHODS: Using a systematic approach based on Aveyard (2014),
      a literature review was conducted which focused on ethical and moral issues,
      nurses and nursing assistants, and the nursing home. FINDINGS: The most salient
      themes identified in the review included clashing ethical principles, issues
      related to communication, lack of resources and quality of care provision. The
      review also identified solutions for overcoming the ethical issues that were
      identified and revealed the definitional challenges that permeate this area of
      work. CONCLUSIONS: The review highlighted a need for improved ethics education
      for care-providers.

PMID- 25870177
TI  - Acupuncture versus usual care for postoperative nausea and vomiting in children
      after tonsillectomy/adenoidectomy: a pragmatic, multicentre, double-blinded,
      randomised trial.
AB  - OBJECTIVES: To investigate the effect of a standardised acupuncture on nausea and
      vomiting in children after tonsillectomy with or without adenoidectomy when
      possible placebo effects were precluded. METHODS: A pragmatic, multicentre,
      double-blinded, randomised controlled trial. The study was conducted over 10
      months in 2012-2013 at three ambulatory clinics. Two hundred and eighty-two
      children, age 1-11 years, American Society of Anesthesiologists grade <=II, were
      included. To equalise expectancy effects, all parents were told that their child
      would receive acupuncture. However, children were randomly allocated to
      perioperative bilateral needling acupuncture at PC6, depth 7 mm, mean time 17 min
      (SD 5-45) during anaesthesia plus usual care, or to usual care only. The regional
      ethics committee approved this approach. Primary endpoints were nausea and
      vomiting 24 h postoperatively. RESULTS: This study did not demonstrate any effect
      of acupuncture (95% CI) compared with standard care. The overall vomiting in the
      acupuncture and usual-care groups was 44.2% and 47.9%, respectively. Nausea was
      experienced by 31.7% in the acupuncture group and by 32.6% in the usual-care
      group. The test power was acceptable for comparisons of vomiting. CONCLUSIONS:
      The findings suggest that when controlling for possible placebo effects
      standardised PC6 acupuncture needling during anaesthesia without further
      stimulation of PC6 is not effective in reducing nausea and vomiting in children
      after tonsillectomy with or without adenoidectomy. Future studies should
      investigate acupuncture treatment which balances adequate dose and technique and
      a feasible, child-friendly acupuncture treatment. TRIAL REGISTRATION NUMBER:
      ClinicalTrials.gov NCT01729052.

PMID- 25870178
TI  - Bent-core liquid crystalline cyanostilbenes: fluorescence switching and
      thermochromism.
AB  - Fluorescent bent-core molecules, bearing one or two cyanostilbene units in the
      lateral structure and different positions of the cyano group (alpha- or beta
      isomers), are described with the aim of modulating the molecular packing and
      fluorescence properties. These compounds give rise to a variety of crystal
      polymorphs and bent-core liquid crystalline phases (SmCP, Colr and B6), offering
      the unique chance to study the fluorescence properties of the cyanostilbene
      structure in different phases. Experimental and computational studies elucidate
      geometrical and electronic properties of these bent-core structures but
      especially the fluorescence properties (spectral positions, quantum yields and
      decay curves), in a detailed comparison between diluted solutions, in
      dichloromethane (DCM) or poly(methylmethacrylate) (PMMA), and condensed phases.
      Quantum yields as high as 70% have been obtained in some diluted solutions (PMMA)
      and condensed phases. Remarkably, the quantum yield values depend on the position
      of the cyano group, being higher for beta- than for the alpha-isomers due to the
      higher radiative rates and lower non-radiative rates of the former. The
      photophysical characterization in the condensed phase focuses on RT studies with
      solid samples and different processing, and show that, upon aggregation,
      interactions between the cyanostilbene groups result in changes of the emission
      spectra and dynamics compared to the diluted systems in DCM and PMMA, giving rise
      to H-aggregations of varying strength. Furthermore, the compounds exhibit
      thermochromism, showing a green-yellow fluorescence in the pristine crystalline
      phase that changes to blue on heating to the liquid crystal phase. 

PMID- 25870179
TI  - Conclusiveness of the Cochrane reviews in gynaecological cancer: A systematic
      analysis.
AB  - OBJECTIVE: To assess the conclusiveness of Cochrane reviews in the field of
      gynaecological cancer. METHODS: The Cochrane Library was searched for reviews
      regarding gynaecological cancer published between 1 January 2000 and 1 November
      2014. Data were extracted from each paper and the conclusiveness of each review
      was assessed. RESULTS: The study included 66 reviews, 41 (62.1%) of which were
      conclusive. Of these, 58 included randomized controlled trials (RCTs), 37 (63.8%)
      of which were conclusive. Conclusive reviews of RCTs included significantly more
      patients than inconclusive reviews, but there was no difference in the number of
      included studies. Of the eight reviews of nonrandomized studies, four (50.0%)
      were conclusive. The majority of reviews recognized the need for additional
      studies. CONCLUSIONS: In the field of gynaecological cancer, reviews are more
      likely to be conclusive when they include RCTs, as well as large numbers of
      patients.

PMID- 25870180
TI  - Correlation between changes in thyromental distance and distance of migration of
      oral Ring-Adair-Elwyn tubes during neck extension with a shoulder positioner in
      patients undergoing neck procedures.
AB  - OBJECTIVES: To measure the migration of oral Ring-Adair-Elwyn (RAE) preformed
      tracheal tubes during neck extension compared with the neutral neck position, and
      to assess the correlation between changes in the thyromental distance (TMD)
      during changes in neck position and tracheal tube migration. METHODS: This
      prospective observational study enrolled adult patients undergoing elective neck
      or thyroid procedures below the mandible. Using fibreoptic bronchoscopy,
      distances from the RAE tube adapter to the carina and to the tube tip were
      measured in the neutral position and after neck extension with a 10 cm D-shaped
      gel shoulder positioner. The change in distance of the RAE tube tip migration was
      compared with the change in TMD in each patient. RESULTS: This study enrolled 106
      patients. During neck extension with a 10-cm shoulder positioner, RAE tubes
      cranially migrated 2.7 cm from the neutral position, but RAE tube migration was
      not correlated with the change in external TMD. CONCLUSION: Oral RAE tube
      migration was not significantly correlated with the change in external TMD. Due
      to their large variability, changes in TMD were not useful predictors of RAE tube
      migration.

PMID- 25870181
TI  - Radiographic patterns of acute chest syndrome.

PMID- 25870182
TI  - Capecitabine-induced ventricular fibrillation arrest: Possible Kounis syndrome.
AB  - We report the case of capecitabine-induced ventricular fibrillation arrest,
      possibly secondary to type I Kounis syndrome. A 47-year-old man with a history of
      T3N1 moderately differentiated adenocarcinoma of the colon, status-post sigmoid
      resection, was started on adjuvant capecitabine approximately five months prior
      to presentation of cardiac arrest secondary to ventricular fibrillation. An
      electrocardiogram (EKG) revealed ST segment elevation on the lateral leads and
      the patient was taken emergently to the cardiac catheterization laboratory. The
      catheterization revealed no angiographically significant stenosis and coronary
      artery disease was ruled out. After ruling out other causes of cardiac arrest,
      the working diagnosis was capecitabine-induced ventricular fibrillation arrest.
      As such, an inflammatory work up was sent to evaluate for the possibility of a
      capecitabine hypersensitivity, or Kounis syndrome, and is the first documented
      report in the literature to do so when evaluating Kounis syndrome. Immunoglobulin
      E (IgE), tryptase, and C-reactive protein were normal but histamine, interleukin
      (IL)-6, and IL-10 were elevated. Histamine elevation supports the suspicion that
      our patient had type I Kounis syndrome. Naranjo adverse drug reaction probability
      scale indicates a probable adverse effect due to capecitabine with seven points.
      A case of capecitabine-induced ventricular fibrillation arrest is reported, with
      a potential for type 1 Kounis syndrome as an underlying pathology supported by
      immunologic work up. 

PMID- 25870183
TI  - Outpatient provider concentration and commercial colonoscopy prices.
AB  - The objective was to evaluate the magnitude of various contributors to outpatient
      commercial colonoscopy prices, including market- and provider-level factors,
      especially market share. We used adjudicated fee-for-service facility claims from
      a large commercial insurer for colonoscopies occurring in hospital outpatient
      department or ambulatory surgery center from October 2005 to December 2012.
      Claims were matched to provider- and market-level data. Linear fixed effects
      regressions of negotiated colonoscopy price were run on provider, system, and
      market characteristics. Markets were defined as counties. There were 178,433
      claims from 169 providers (104 systems). The mean system market share was 76% (SD
      = 0.34) and the mean real (deflated) price was US$1363 (SD = 374), ranging from
      US$169 to US$2748. For every percentage point increase in a system or individual
      facility's bed share, relative price increased by 2 to 4 percentage points; this
      result was stable across a number of specifications. Market population and price
      were also consistently positively related, though this relation was small in
      magnitude. No other factor explained price as strongly as market share. Price
      variation for colonoscopy was driven primarily by market share, of particular
      concern as the number of mergers increases in wake of the recession and the
      Affordable Care Act. Whether variation is justified by better quality care
      requires further research to determine whether quality is subsumed in prices.

PMID- 25870185
TI  - Cytosolic Hsp60 orchestrates the survival and inflammatory responses of vascular
      smooth muscle cells in injured aortic vessels.
AB  - AIMS: Pro-inflammatory response of vascular smooth muscle cells (VSMCs) is
      triggered by endothelial damage and a causative step for thrombosis and
      neointimal thickening in the injured arterial vessels. Therefore, we investigate
      a role of cytosolic Hsp60 as a novel pro-inflammatory mediator in VSMCs. METHODS
      AND RESULTS: Hsp60 was detected in the cytosol of VSMCs. The selective depletion
      of cytosolic Hsp60 in VSMCs reduced the IkappaB kinase activation, repressed the
      induction of nuclear factor (NF)-kappaB-dependent survival genes (MnSOD and Bfl
      1/A1), and enhanced apoptotic death in response to TNF-alpha. Moreover, a
      quantitative RNA sequencing revealed that the expression of 75 genes among the
      774 TNF-alpha-inducible genes was significantly reduced by the depletion of
      cytosolic Hsp60. In particular, the expression of pro-inflammatory
      cytokines/chemokines, such as CCL2, CCL20, and IL-6, was regulated by the
      cytosolic Hsp60 in VSMCs. Finally, the depletion of cytosolic Hsp60 markedly
      inhibited the neointimal thickening in the balloon-injured arterial vessels by
      inducing apoptotic cell death and inhibiting chemokine production. CONCLUSIONS:
      This study provides the first evidence that cytosolic Hsp60 could be a
      therapeutic target for preventing VSMC hyperplasia and inflammatory response in
      the injured vessels.

PMID- 25870184
TI  - Cardioprotection by H2S engages a cGMP-dependent protein kinase G/phospholamban
      pathway.
AB  - AIMS: H2S is known to confer cardioprotection; however, the pathways mediating
      its effects in vivo remain incompletely understood. The purpose of the present
      study is to evaluate the contribution of cGMP-regulated pathways in the infarct
      limiting effect of H2S in vivo. METHODS AND RESULTS: Anaesthetized rabbits were
      subjected to myocardial ischaemia (I)/reperfusion (R), and infarct size was
      determined in control or H2S-exposed groups. The H2S donor sodium hydrosulfide
      (NaHS, an agent that generates H2S) increased cardiac cGMP and reduced the
      infarct size. The cGMP-dependent protein kinase (PKG)-I inhibitor DT2 abrogated
      the protective effect of NaHS, whereas the control peptide TAT or l-nitroarginine
      methyl ester (l-NAME) did not alter the effect of NaHS. Moreover, the KATP
      channel inhibitor, glibenclamide, partially reversed the effects of NaHS, whereas
      inhibition of mitochondrial KATP did not modify the NaHS response. NaHS enhanced
      phosphorylation of phospholamban (PLN), in a PKG-dependent manner. To further
      investigate the role of PLN in H2S-mediated cardioprotection, wild-type and PLN
      KO mice underwent I/R. NaHS did not exert cardioprotection in PLN KO mice. Unlike
      what was observed in rabbits, genetic or pharmacological inhibition of eNOS
      abolished the infarct-limiting effect of NaHS in mice. CONCLUSIONS: Our findings
      demonstrate (i) that administration of NaHS induces cardioprotection via a
      cGMP/PKG/PLN pathway and (ii) contribution of nitric oxide to the H2S response is
      species-specific.

PMID- 25870186
TI  - Comprehensive T wave morphology assessment in a randomized clinical study of
      dofetilide, quinidine, ranolazine, and verapamil.
AB  - BACKGROUND: Congenital long QT syndrome type 2 (abnormal hERG potassium channel)
      patients can develop flat, asymmetric, and notched T waves. Similar observations
      have been made with a limited number of hERG-blocking drugs. However, it is not
      known how additional calcium or late sodium block, that can decrease torsade
      risk, affects T wave morphology. METHODS AND RESULTS: Twenty-two healthy subjects
      received a single dose of a pure hERG blocker (dofetilide) and 3 drugs that also
      block calcium or sodium (quinidine, ranolazine, and verapamil) as part of a 5
      period, placebo-controlled cross-over trial. At pre-dose and 15 time-points post
      dose, ECGs and plasma drug concentration were assessed. Patch clamp experiments
      were performed to assess block of hERG, calcium (L-type) and late sodium currents
      for each drug. Pure hERG block (dofetilide) and strong hERG block with lesser
      calcium and late sodium block (quinidine) caused substantial T wave morphology
      changes (P<0.001). Strong late sodium current and hERG block (ranolazine) still
      caused T wave morphology changes (P<0.01). Strong calcium and hERG block
      (verapamil) did not cause T wave morphology changes. At equivalent QTc
      prolongation, multichannel blockers (quinidine and ranolazine) caused equal or
      greater T wave morphology changes compared with pure hERG block (dofetilide).
      CONCLUSIONS: T wave morphology changes are directly related to amount of hERG
      block; however, with quinidine and ranolazine, multichannel block did not prevent
      T wave morphology changes. A combined approach of assessing multiple ion
      channels, along with ECG intervals and T wave morphology may provide the greatest
      insight into drug-ion channel interactions and torsade de pointes risk. CLINICAL
      TRIAL REGISTRATION: URL: http://clinicaltrials.gov/ Unique identifier:
      NCT01873950.

PMID- 25870187
TI  - Racial differences in clinical treatment and self-care behaviors of adults with
      chronic heart failure.
AB  - BACKGROUND: In the United States, the highest prevalence of heart failure (HF) is
      in blacks followed by whites. Compared with whites, blacks have a higher risk of
      HF-related morbidity and mortality and HF-related hospitalization. Little
      research has focused on explaining the reasons for these disparities. The purpose
      of this study was to examine racial differences in demographic and clinical
      characteristics in blacks and whites with HF and to determine if these
      characteristics influenced treatment, or together with treatment, influenced self
      care behaviors. METHODS AND RESULTS: This was a secondary analysis of existing
      data collected from adults (n=272) with chronic HF enrolled from outpatient sites
      in the northeastern United States and followed for 6 months. After adjusting for
      sociodemographic and clinical characteristics within reduced (HFrEF) and
      preserved ejection fraction (HFpEF) groups, there were 2 significant racial
      differences in clinical treatment. Blacks with HFrEF were prescribed ACE
      inhibitors and hydralazine and isosorbide dinitrate (H-ISDN) more often than
      whites. In the HFpEF group, blacks were taking more medications and were
      prescribed digoxin and a diuretic when symptomatic. Deficits in HF knowledge and
      decreased medication adherence, objectively measured, were more prominent in
      blacks. These racial differences were not explained by sociodemographic or
      clinical characteristics or clinical treatment variables. Premorbid intellect and
      the quality of support received contributed to clinical treatment and self-care.
      CONCLUSION: Although few differences in clinical treatment could be attributed
      solely to race, knowledge about HF and medication adherence is lower in blacks
      than whites. Further research is needed to explain these observations, which may
      be targets for future intervention research.

PMID- 25870188
TI  - Effect of bilateral carotid body resection on cardiac baroreflex control of blood
      pressure during hypoglycemia.
AB  - Hypoglycemia results in a reduction in cardiac baroreflex sensitivity and a shift
      in the baroreflex working range to higher heart rates. This effect is mediated,
      in part, by the carotid chemoreceptors. Therefore, we hypothesized hypoglycemia
      mediated changes in baroreflex control of heart rate would be blunted in carotid
      body-resected patients when compared with healthy controls. Five patients with
      bilateral carotid body resection for glomus tumors and 10 healthy controls
      completed a 180-minute hyperinsulinemic, hypoglycemic (~3.3 mmol/L) clamp.
      Changes in heart rate, blood pressure, and spontaneous cardiac baroreflex
      sensitivity were assessed. Baseline baroreflex sensitivity was not different
      between groups (P>0.05). Hypoglycemia resulted in a reduction in baroreflex
      sensitivity in both the groups (main effect of time, P<0.01) and responses were
      lower in resected patients when compared with controls (main effect of group,
      P<0.05). Hypoglycemia resulted in large reductions in systolic (-17+/-7 mm Hg)
      and mean (-14+/-5 mm Hg) blood pressure in resected patients that were not
      observed in controls (interaction of group and time, P<0.05). Despite lower blood
      pressures, increases in heart rate with hypoglycemia were blunted in resected
      patients (interaction of group and time, P<0.01). Major novel findings from this
      study demonstrate that intact carotid chemoreceptors are essential for increasing
      heart rate and maintaining arterial blood pressure during hypoglycemia in humans.
      These data support a contribution of the carotid chemoreceptors to blood pressure
      control and highlight the potential widespread effects of carotid body resection
      in humans.

PMID- 25870189
TI  - Angiotensin II activates the RhoA exchange factor Arhgef1 in humans.
AB  - Although a causative role for RhoA-Rho kinase has been recognized in the
      development of human hypertension, the molecular mechanism(s) and the RhoA
      guanine exchange factor(s) responsible for the overactivation of RhoA remain
      unknown. Arhgef1 was identified as a RhoA guanine exchange factor involved in
      angiotensin II (Ang II)-mediated regulation of vascular tone and hypertension in
      mice. The aim of this study was to determine whether Arhgef1 is activated and
      involved in the activation of RhoA-Rho kinase signaling by Ang II in humans. In
      vitro stimulation of human coronary artery smooth muscle cells and human
      peripheral blood mononuclear cells by Ang II (0.1 MUmol/L) induced activation of
      Arhgef1 attested by its increased tyrosine phosphorylation. Silencing of Arhgef1
      expression by siRNA inhibited Ang II-induced activation of RhoA-Rho kinase
      signaling. In normotensive subjects, activation of the renin-angiotensin system
      by a low-salt diet for 7 days increased RhoA-Rho kinase signaling and stimulated
      Arhgef1 activity in peripheral blood mononuclear cells. In conclusion, our
      results strongly suggest that Arhgef1 mediates Ang II-induced RhoA activation in
      humans. Moreover, they show that measurement of RhoA guanine exchange factor
      activity in peripheral blood mononuclear cells might be a useful method to
      evaluate RhoA guanine exchange factor activity in humans.

PMID- 25870190
TI  - G protein-coupled receptor kinase 4: role in hypertension.

PMID- 25870191
TI  - Apathy towards ambulatory blood pressure monitoring use in hypertension: is it
      due to cognitive dissonance, money, or both?

PMID- 25870192
TI  - Pressure overload, sympathetic drive, and inflammation: is ghrelin the link?

PMID- 25870194
TI  - Strategies for classifying patients based on office, home, and ambulatory blood
      pressure measurement.
AB  - Hypertension guidelines propose home or ambulatory blood pressure monitoring as
      indispensable after office measurement. However, whether preference should be
      given to home or ambulatory monitoring remains undetermined. In 831 untreated
      outpatients (mean age, 50.6 years; 49.8% women), we measured office (3 visits),
      home (7 days), and 24-h ambulatory blood pressures. We applied hypertension
      guidelines for cross-classification of patients into normotension or white-coat,
      masked, or sustained hypertension. Based on office and home blood pressures, the
      prevalence of white-coat, masked, and sustained hypertension was 61 (10.3%), 166
      (20.0%), and 162 (19.5%), respectively. Using daytime (from 8 am to 6 pm) instead
      of home blood pressure confirmed the cross-classification in 575 patients
      (69.2%), downgraded risk from masked hypertension to normotension (n=24) or from
      sustained to white-coat hypertension (n=9) in 33 (4.0%), but upgraded risk from
      normotension to masked hypertension (n=179) or from white-coat to sustained
      hypertension (n=44) in 223 (26.8%). Analyses based on 24-h ambulatory blood
      pressure were confirmatory. In adjusted analyses, both the urinary albumin-to
      creatinine ratio (+20.6%; confidence interval, 4.4-39.3) and aortic pulse wave
      velocity (+0.30 m/s; confidence interval, 0.09-0.51) were higher in patients who
      moved up to a higher risk category. Both indexes of target organ damage and
      central augmentation index were positively associated (P<=0.048) with the odds of
      being reclassified. In conclusion, for reliably diagnosing hypertension and
      starting treatment, office measurement should be followed by ambulatory blood
      pressure monitoring. Using home instead of ambulatory monitoring misses the high
      risk diagnoses of masked or sustained hypertension in over 25% of patients. 

PMID- 25870193
TI  - Gut dysbiosis is linked to hypertension.
AB  - Emerging evidence suggests that gut microbiota is critical in the maintenance of
      physiological homeostasis. This study was designed to test the hypothesis that
      dysbiosis in gut microbiota is associated with hypertension because genetic,
      environmental, and dietary factors profoundly influence both gut microbiota and
      blood pressure. Bacterial DNA from fecal samples of 2 rat models of hypertension
      and a small cohort of patients was used for bacterial genomic analysis. We
      observed a significant decrease in microbial richness, diversity, and evenness in
      the spontaneously hypertensive rat, in addition to an increased
      Firmicutes/Bacteroidetes ratio. These changes were accompanied by decreases in
      acetate- and butyrate-producing bacteria. In addition, the microbiota of a small
      cohort of human hypertensive patients was found to follow a similar dysbiotic
      pattern, as it was less rich and diverse than that of control subjects. Similar
      changes in gut microbiota were observed in the chronic angiotensin II infusion
      rat model, most notably decreased microbial richness and an increased
      Firmicutes/Bacteroidetes ratio. In this model, we evaluated the efficacy of oral
      minocycline in restoring gut microbiota. In addition to attenuating high blood
      pressure, minocycline was able to rebalance the dysbiotic hypertension gut
      microbiota by reducing the Firmicutes/Bacteroidetes ratio. These observations
      demonstrate that high blood pressure is associated with gut microbiota dysbiosis,
      both in animal and human hypertension. They suggest that dietary intervention to
      correct gut microbiota could be an innovative nutritional therapeutic strategy
      for hypertension.

PMID- 25870195
TI  - Endogenous ghrelin attenuates pressure overload-induced cardiac hypertrophy via a
      cholinergic anti-inflammatory pathway.
AB  - Cardiac hypertrophy, which is commonly caused by hypertension, is a major risk
      factor for heart failure and sudden death. Endogenous ghrelin has been shown to
      exert a beneficial effect on cardiac dysfunction and postinfarction remodeling
      via modulation of the autonomic nervous system. However, ghrelin's ability to
      attenuate cardiac hypertrophy and its potential mechanism of action are unknown.
      In this study, cardiac hypertrophy was induced by transverse aortic constriction
      in ghrelin knockout mice and their wild-type littermates. After 12 weeks, the
      ghrelin knockout mice showed significantly increased cardiac hypertrophy compared
      with wild-type mice, as evidenced by their significantly greater heart
      weight/tibial length ratios (9.2+/-1.9 versus 7.9+/-0.8 mg/mm), left ventricular
      anterior wall thickness (1.3+/-0.2 versus 1.0+/-0.2 mm), and posterior wall
      thickness (1.1+/-0.3 versus 0.9+/-0.1 mm). Furthermore, compared with wild-type
      mice, ghrelin knockout mice showed suppression of the cholinergic anti
      inflammatory pathway, as indicated by reduced parasympathetic nerve activity and
      higher plasma interleukin-1beta and interleukin-6 levels. The administration of
      either nicotine or ghrelin activated the cholinergic anti-inflammatory pathway
      and attenuated cardiac hypertrophy in ghrelin knockout mice. In conclusion, our
      results show that endogenous ghrelin plays a crucial role in the progression of
      pressure overload-induced cardiac hypertrophy via a mechanism that involves the
      activation of the cholinergic anti-inflammatory pathway.

PMID- 25870197
TI  - Association studies suggest a key role for endothelin-1 in the pathogenesis of
      preeclampsia and the accompanying renin-angiotensin-aldosterone system
      suppression.
AB  - Women with preeclampsia display low renin-angiotensin-aldosterone system activity
      and a high antiangiogenic state, the latter characterized by high levels of
      soluble Fms-like tyrosine kinase (sFlt)-1 and reduced placental growth factor
      levels. To investigate whether renin-angiotensin-aldosterone system suppression
      in preeclampsia is because of this disturbed angiogenic balance, we measured mean
      arterial pressure, creatinine, endothelin-1 (ET-1), and renin-angiotensin
      aldosterone system components in pregnant women with a high (>=85; n=38) or low
      (<85; n=65) soluble Fms-like tyrosine kinase-1/placental growth factor ratio.
      Plasma ET-1 levels were increased in women with a high ratio, whereas their
      plasma renin activity and plasma concentrations of renin, angiotensinogen, and
      aldosterone were decreased. Plasma renin activity-aldosterone relationships were
      identical in both the groups. Multiple regression analysis revealed that plasma
      renin concentration correlated independently with mean arterial pressure and
      plasma ET-1. Plasma ET-1 correlated positively with soluble Fms-like tyrosine
      kinase-1 and negatively with plasma renin concentration, and urinary protein
      correlated with plasma ET-1 and mean arterial pressure. Despite the lower plasma
      levels of renin and angiotensinogen in the high-ratio group, their urinary levels
      of these components were elevated. Correction for albumin revealed that this was
      because of increased glomerular filtration. Subcutaneous arteries obtained from
      patients with preeclampsia displayed an enhanced, AT2 receptor-mediated response
      to angiotensin II. In conclusion, a high antiangiogenic state associates with ET
      1 activation, which together with the increased mean arterial pressure may
      underlie the parallel reductions in renin and aldosterone in preeclampsia.
      Because ET-1 also was a major determinant of urinary protein, our data reveal a
      key role for ET-1 in the pathogenesis of preeclampsia. Finally, the enhanced
      angiotensin responsiveness in preeclampsia involves constrictor AT2 receptors.

PMID- 25870196
TI  - 6beta-hydroxytestosterone, a cytochrome P450 1B1 metabolite of testosterone,
      contributes to angiotensin II-induced hypertension and its pathogenesis in male
      mice.
AB  - Previously, we showed that Cyp1b1 gene disruption minimizes angiotensin II
      induced hypertension and associated pathophysiological changes in male mice. This
      study was conducted to test the hypothesis that cytochrome P450 1B1-generated
      metabolites of testosterone, 6beta-hydroxytestosterone and 16alpha
      hydroxytestosterone, contribute to angiotensin II-induced hypertension and its
      pathogenesis. Angiotensin II infusion for 2 weeks increased cardiac cytochrome
      P450 1B1 activity and plasma levels of 6beta-hydroxytestosterone, but not 16alpha
      hydroxytestosterone, in Cyp1b1(+/+) mice without altering Cyp1b1 gene expression;
      these effects of angiotensin II were not observed in Cyp1b1(-/-) mice.
      Angiotensin II-induced increase in systolic blood pressure and associated cardiac
      hypertrophy, and fibrosis, measured by intracardiac accumulation of alpha-smooth
      muscle actin, collagen, and transforming growth factor-beta, and increased
      nicotinamide adenine dinucleotide phosphate oxidase activity and production of
      reactive oxygen species; these changes were minimized in Cyp1b1(-/-) or castrated
      Cyp1b1(+/+) mice, and restored by treatment with 6beta-hydroxytestoterone. In
      Cyp1b1(+/+) mice, 6beta-hydroxytestosterone did not alter the angiotensin II
      induced increase in systolic blood pressure; the basal systolic blood pressure
      was also not affected by this agent in either genotype. Angiotensin II or
      castration did not alter cardiac, angiotensin II type 1 receptor, angiotensin
      converting enzyme, Mas receptor, or androgen receptor mRNA levels in Cyp1b1(+/+)
      or in Cyp1b1(-/-) mice. These data suggest that the testosterone metabolite,
      6beta-hydroxytestosterone, contributes to angiotensin II-induced hypertension and
      associated cardiac pathogenesis in male mice, most probably by acting as a
      permissive factor. Moreover, cytochrome P450 1B1 could serve as a novel target
      for developing agents for treating renin-angiotensin and testosterone-dependent
      hypertension and associated pathogenesis in males.

PMID- 25870198
TI  - Inflammatory bowel disease and the elderly: a review.
AB  - Inflammatory bowel disease among the elderly is common, with growing incident and
      prevalence rates. Compared with younger IBD patients, genetics contribute less to
      the pathogenesis of older-onset IBD, with dysbiosis and dysregulation of the
      immune system playing a more significant role. Diagnosis may be difficult in
      older individuals, as multiple other common diseases can mimic IBD in this
      population. The clinical manifestations in older-onset IBD are distinct, and
      patients tend to have less of a disease trajectory. Despite multiple effective
      medical and surgical treatment strategies for adults with Crohn's disease and
      ulcerative colitis, efficacy studies typically have excluded older subjects. A
      rapidly ageing population and increasing rates of Crohn's and ulcerative colitis
      make the paucity of data in older adults with IBD an increasingly important
      clinical issue. 

PMID- 25870199
TI  - Biomechanical forces promote blood development through prostaglandin E2 and the
      cAMP-PKA signaling axis.
AB  - Blood flow promotes emergence of definitive hematopoietic stem cells (HSCs) in
      the developing embryo, yet the signals generated by hemodynamic forces that
      influence hematopoietic potential remain poorly defined. Here we show that fluid
      shear stress endows long-term multilineage engraftment potential upon early
      hematopoietic tissues at embryonic day 9.5, an embryonic stage not previously
      described to harbor HSCs. Effects on hematopoiesis are mediated in part by a
      cascade downstream of wall shear stress that involves calcium efflux and
      stimulation of the prostaglandin E2 (PGE2)-cyclic adenosine monophosphate (cAMP)
      protein kinase A (PKA) signaling axis. Blockade of the PGE2-cAMP-PKA pathway in
      the aorta-gonad-mesonephros (AGM) abolished enhancement in hematopoietic
      activity. Furthermore, Ncx1 heartbeat mutants, as well as static cultures of AGM,
      exhibit lower levels of expression of prostaglandin synthases and reduced
      phosphorylation of the cAMP response element-binding protein (CREB). Similar to
      flow-exposed cultures, transient treatment of AGM with the synthetic analogue
      16,16-dimethyl-PGE2 stimulates more robust engraftment of adult recipients and
      greater lymphoid reconstitution. These data provide one mechanism by which
      biomechanical forces induced by blood flow modulate hematopoietic potential. 

PMID- 25870202
TI  - The Role of Body Image in the Link Between ADHD and Depression Symptoms Among
      College Students.
AB  - OBJECTIVE: Given the link between negative body image and depression symptoms,
      body image may affect the association between ADHD and depression symptoms. We
      evaluated the degree to which a variety of body image constructs mediated the
      association between ADHD and depression symptoms. METHOD: Participants were
      undergraduate psychology students ( N = 627, age: M = 20.23, SD = 1.40, 60%
      female, 47% European American) who completed an online assessment. RESULTS:
      Results indicated that ADHD symptoms were indirectly associated with increased
      depression symptoms, and that negative evaluation of physical appearance,
      overweight preoccupation, and body dissatisfaction mediated the association
      between ADHD and depression symptoms. ADHD symptoms were also directly associated
      with increased depression symptoms. CONCLUSION: Body image appears to play a role
      in the association between ADHD and depression symptoms for college students.
      Implications for future research and clinical practice are discussed.

PMID- 25870200
TI  - Adenosine signaling promotes hematopoietic stem and progenitor cell emergence.
AB  - Hematopoietic stem cells (HSCs) emerge from aortic endothelium via the
      endothelial-to-hematopoietic transition (EHT). The molecular mechanisms that
      initiate and regulate EHT remain poorly understood. Here, we show that adenosine
      signaling regulates hematopoietic stem and progenitor cell (HSPC) development in
      zebrafish embryos. The adenosine receptor A2b is expressed in the vascular
      endothelium before HSPC emergence. Elevated adenosine levels increased
      runx1(+)/cmyb(+) HSPCs in the dorsal aorta, whereas blocking the adenosine
      pathway decreased HSPCs. Knockdown of A2b adenosine receptor disrupted scl(+)
      hemogenic vascular endothelium and the subsequent EHT process. A2b adenosine
      receptor activation induced CXCL8 via cAMP-protein kinase A (PKA) and mediated
      hematopoiesis. We further show that adenosine increased multipotent progenitors
      in a mouse embryonic stem cell colony-forming assay and in embryonic day 10.5
      aorta-gonad-mesonephros explants. Our results demonstrate that adenosine
      signaling plays an evolutionary conserved role in the first steps of HSPC
      formation in vertebrates.

PMID- 25870203
TI  - Behavioral Observations of Parents With ADHD During Parent Training.
AB  - OBJECTIVE: Several studies suggest that parental ADHD impedes behavioral parent
      training (BPT) outcomes. Parental ADHD symptoms exhibited during BPT may
      interfere with the acquisition of new skills. This study explored the observed
      behavior of parents with ADHD during BPT. METHOD: Parents of children with ADHD
      attending group BPT completed self-ratings of their ADHD symptoms. Parents
      indicating a moderate level of ADHD symptoms were administered a clinical
      interview, and 37.3% of parents met ADHD criteria based on Diagnostic and
      Statistical Manual of Mental Disorders (4th ed.; DSM-IV) clinician-rated symptom
      counts. RESULTS: Parents with high ADHD symptoms displayed more total and off
      task violations compared with parents with low ADHD symptoms, although no
      significant differences emerged for other behaviors (i.e., working quietly, using
      materials appropriately, and remaining in seat), absences, or tardiness.
      CONCLUSION: Parental ADHD symptoms were manifested during BPT. Future research
      should clarify the nature of parental behavior in BPT as a possible mechanism
      explaining the relation between parental ADHD and impaired BPT outcomes.

PMID- 25870201
TI  - Flow-induced protein kinase A-CREB pathway acts via BMP signaling to promote HSC
      emergence.
AB  - Fluid shear stress promotes the emergence of hematopoietic stem cells (HSCs) in
      the aorta-gonad-mesonephros (AGM) of the developing mouse embryo. We determined
      that the AGM is enriched for expression of targets of protein kinase A (PKA)-cAMP
      response element-binding protein (CREB), a pathway activated by fluid shear
      stress. By analyzing CREB genomic occupancy from chromatin-immunoprecipitation
      sequencing (ChIP-seq) data, we identified the bone morphogenetic protein (BMP)
      pathway as a potential regulator of CREB. By chemical modulation of the PKA-CREB
      and BMP pathways in isolated AGM VE-cadherin(+) cells from mid-gestation embryos,
      we demonstrate that PKA-CREB regulates hematopoietic engraftment and
      clonogenicity of hematopoietic progenitors, and is dependent on secreted BMP
      ligands through the type I BMP receptor. Finally, we observed blunting of this
      signaling axis using Ncx1-null embryos, which lack a heartbeat and intravascular
      flow. Collectively, we have identified a novel PKA-CREB-BMP signaling pathway
      downstream of shear stress that regulates HSC emergence in the AGM via the
      endothelial-to-hematopoietic transition.

PMID- 25870204
TI  - The future of transcatheter mitral valve interventions: competitive or
      complementary role of repair vs. replacement?
AB  - Transcatheter mitral interventions has been developed to address an unmet
      clinical need and may be an alternative therapeutic option to surgery with the
      intent to provide symptomatic and prognostic benefit. Beyond MitraClip therapy,
      alternative repair technologies are being developed to expand the transcatheter
      intervention armamentarium. Recently, the feasibility of transcatheter mitral
      valve implantation in native non-calcified valves has been reported in very high
      risk patients. Acknowledging the lack of scientific evidence to date, it is
      difficult to predict what the ultimate future role of transcatheter mitral valve
      interventions will be. The purpose of the present report is to review the current
      state-of-the-art of mitral valve intervention, and to identify the potential
      future scenarios, which might benefit most from the transcatheter repair and
      replacement devices under development. 

PMID- 25870205
TI  - Mechanical Force-induced TGFB1 Increases Expression of SOST/POSTN by hPDL Cells.
AB  - The aim of this study was to investigate the response of human periodontal
      ligament (hPDL) fibroblasts to an intermittent compressive force and its effect
      on the expression of SOST, POSTN, and TGFB1. A computerized cell compressive
      force loading apparatus was introduced, and hPDL cells were subjected to
      intermittent compressive force. The changes in messenger RNA (mRNA) and protein
      expression were monitored by real-time polymerase chain reaction and Western blot
      analysis, respectively. An increased expression of SOST, POSTN, and TGFB1 was
      observed in a time-dependent fashion. Addition of cycloheximide, a transforming
      growth factor (TGF)-beta inhibitor (SB431542), or a neutralizing antibody against
      TGF-beta1 attenuated the force-induced expression of SOST and POSTN as well as
      sclerostin and periostin, indicating a role of TGF-beta1 in the pressure-induced
      expression of these proteins. Enzyme-linked immunosorbent assay analysis revealed
      an increased level of TGF-beta1 in the cell extracts but not in the medium,
      suggesting that intermittent compressive force promoted the accumulation of TGF
      beta1 in the cells or their surrounding matrix. In conclusion, an intermittent
      compressive force regulates SOST/POSTN expression by hPDL cells via the TGF-beta1
      signaling pathway. Since these proteins play important roles in the homeostasis
      of the periodontal tissue, our results indicate the importance of masticatory
      forces in this process. 

PMID- 25870206
TI  - The ongoing search for the molecular basis of plant osmosensing.

PMID- 25870208
TI  - Perspectives on: The response to osmotic challenges.

PMID- 25870207
TI  - Cell volume control in three dimensions: Water movement without solute movement.

PMID- 25870209
TI  - Bacterial responses to osmotic challenges.

PMID- 25870210
TI  - H1N1 pneumonitis associated with long-term non-steroidal anti-inflammatory drug
      abuse.
AB  - This case series discusses two similar presentations of H1N1 influenza in young
      patients with a background history of long-term non-steroidal anti-inflammatory
      drug (NSAID) abuse. Both patients presented with type 1 respiratory failure
      requiring intensive care unit admission and subsequent organ support. This report
      reviews the immunosuppressive effects of long-term NSAID use and highlights a
      potential link to the significant morbidity seen. 

PMID- 25870211
TI  - Migrated biliary stent causing perforation of sigmoid colon and pelvic abscess.
AB  - Endoscopically placed biliary stents are a well-established procedure for the
      treatment of benign and malignant causes of obstructive jaundice. A plastic stent
      is usually inserted in patients with obstructive jaundice due to pancreatic
      cancer as a short-term procedure. Stent migration has been reported as a
      complication, although in most cases the stent will pass through or remain in the
      bowel lumen for a period of time. In rare cases, the stent may cause sigmoid
      perforation and pelvic abscess formation, especially in patients with sigmoid
      diverticulae or abdominal adhesions due to previous surgery. We present a patient
      with sigmoid perforation and pelvic abscess due to distal migration of a biliary
      stent placed to decompress a pancreatic head carcinoma. 

PMID- 25870212
TI  - Fish Malodour syndrome in a child.
AB  - Body odour can be a manifestation of several metabolic diseases. Diagnosis may be
      difficult because the disease is often unknown to the doctor. We present a child
      observed in a general paediatric clinic for bad body odour after eating fish.
      Given the suspicion of trimethylaminuria, molecular study of flavin mono
      oxygenase 3 gene was requested. A pathogenic mutation and polymorphism were
      identified, which could explain the complaint. Dietary and hygienic measures were
      imposed with symptom improvement. 

PMID- 25870213
TI  - Actinomyces meyeri brain abscess following dental extraction.
AB  - We describe the rare occurrence of an Actinomyces meyeri cerebral abscess in a 55
      year-old woman following a dental extraction. This patient presented with a 2-day
      history of hemisensory loss, hyper-reflexia and retro-orbital headache, 7 days
      following a dental extraction for apical peridonitis. Neuroimaging showed a large
      left parietal abscess with surrounding empyema. The patient underwent craniotomy
      and drainage of the abscess. A. meyeri was cultured. Actinomycosis is a rare
      cause of cerebral abscess. The A. meyeri subtype is particularly rare, accounting
      for less than 1% of specimens. This case describes an unusually brief course of
      the disease, which is usually insidious. Parietal lobe involvement is unusual as
      cerebral abscesses usually have a predilection for the frontal and temporal
      regions of the brain. Although there are no randomised trials to guide therapy,
      current consensus is to use a prolonged course of intravenous antibiotics,
      followed by 6-12 months of oral therapy.

PMID- 25870214
TI  - Haemophagocytic lymphohistiocytosis associated with Mycobacterium tuberculosis
      infection.
AB  - Haemophagocytic lymphohistiocytosis (HLH) is a rare, potentially fatal condition
      that can be primary or secondary. Secondary HLH can occur in association with
      infections, most commonly viral infections, but has also been reported in
      association with Mycobacterium tuberculosis (TB). Prompt identification of the
      underlying cause of HLH is important as it guides treatment decisions. Early
      initiation of appropriate treatment (eg, anti-TB treatment) reduces morbidity and
      mortality. We present a case of HLH associated with TB infection. Initial TB
      investigations were negative and standard combination chemoimmunotherapy for HLH
      resulted in a limited clinical response. On apparent relapse of HLH, further
      investigation revealed TB with changes on CT chest, granuloma on bone marrow and
      eventual positive TB culture on bronchoalveolar lavage. Subsequent treatment with
      quadruple anti-TB treatment resulted in rapid clinical response and disease
      remission. We advocate continued monitoring for TB infection in patients with
      HLH, and prophylaxis or full treatment for those at high risk. 

PMID- 25870215
TI  - Anti-VEGF therapy in a silicone oil-filled myopic eye with choroidal
      neovascularisation.
AB  - A 33-year-old man presented with vision loss in his right eye due to
      rhegmatogenous retinal detachment, for which he underwent pars plana vitrectomy
      with silicone oil injection. Three months later, the patient presented with
      sudden vision loss. On examination, his visual acuity was 20/200 with presence of
      subretinal haemorrhage with attached retina and silicone oil in situ. Fluorescein
      angiography confirmed the diagnosis of choroidal neovascularisation (CNV). The
      patient underwent intravitreal ranibizumab injection (0.5 mg per 0.05 mL). He
      subsequently underwent oil removal along with intravitreal bevacizumab injection
      (1.25 mg per 0.05 mL). The CNV completely regressed. At 7 years follow-up, the
      patient's best corrected visual acuity was 20/50 with attached retina and macular
      scar due to regressed CNV. His other eye was within normal limits throughout the
      follow-up period. This unique case demonstrates the successful outcome of
      intravitreal ranibizumab injection in a silicone oil-filled eye with myopic CNV.

PMID- 25870216
TI  - Chronic candida endophthalmitis as a cause of intermediate uveitis.
AB  - Intermediate uveitis is a subset of intraocular inflammation where vitritis is
      the most consistent sign, with or without snowball opacities or snow banks over
      the pars plana. Some patients will have an associated underlying systemic disease
      such as sarcoidosis, multiple sclerosis, ocular tuberculosis, inflammatory bowel
      disease, possibly Behcet's disease and intraocular lymphoma, whereas some will be
      classified as pars planitis in case of the lack of an identifiable systemic
      disease association. Our patient, a 47-year-old woman, developed intermediate
      uveitis after cataract surgery in her right eye, was misdiagnosed as pars
      planitis, and received steroid monotherapy for 8 months. Her inflammation only
      fully resolved after vitrectomy with removal of the intraocular lens (IOL) and
      capsular bag. Oral fluconazole and intravitreal amphotericin B injection had
      failed to resolve her inflammation when Candida albicans was identified as the
      cause of her persistent intermediate uveitis.

PMID- 25870217
TI  - Patient and tumour characteristics as prognostic markers for oesophageal cancer:
      a retrospective analysis of a cohort of patients at Groote Schuur Hospital.
AB  - OBJECTIVES: In addition to the high incidence of squamous carcinoma of the
      oesophagus among South African men, the neoplasm is also characterized by an
      exceptionally latent course and poor prognosis. The aim of this study was to
      review a cohort of patients with carcinoma of the oesophagus presenting to the
      Groote Schuur Hospital, Cape Town and evaluate patient and tumour characteristics
      for their role as prognostic markers for survival. METHODS: Information on
      patients was extracted from a database established and maintained over a 30-year
      period. Information for the analysis included patient demographics, clinical
      symptoms at presentation, tumour characteristics and treatment decisions.
      Statistical analyses were performed using GraphPad Prism 5 applying chi-square
      and Kaplan-Meier tests. RESULTS: Data were available on 1868 patients. The
      majority of patients were Black African men and the predominant histology was
      squamous cell carcinoma. There were significant differences (P < 0.05) in the
      survival of patients with respect to race (P < 0.001), performance status (P <
      0.001), weight loss (P = 0.001) and prior tuberculosis diagnosis (P = 0.007).
      Tumour characteristics that were significantly associated with survival were
      histological type, tumour size and site. Gender, prior cancer, smoking status and
      tumour-related pain did not show significant association with survival in
      patients with oesophageal cancer. Only 19.8% of the patients were candidates for
      potentially curative treatment. CONCLUSIONS: This analysis shows that there are
      prominent patient and tumour characteristics that are significantly associated
      with survival with respect to oesophageal carcinoma. The inclusion of these
      factors in the initial assessment of patients may assist with appropriate
      treatment decisions.

PMID- 25870219
TI  - Unilateral lung injury after minimally invasive cardiac surgery: more questions
      than answers.

PMID- 25870218
TI  - Suction on chest drains following lung resection: evidence and practice are not
      aligned.
AB  - OBJECTIVES: A best evidence topic in Interactive CardioVascular and Thoracic
      Surgery (2006) looked at application of suction to chest drains following
      pulmonary lobectomy. After screening 391 papers, the authors analysed six studies
      (five randomized controlled trials [RCTs]) and found no evidence in favour of
      postoperative suction in terms of air leak duration, time to chest drain removal
      or length of stay. Indeed, suction was found to be detrimental in four studies.
      We sought to determine whether clinical practice is consistent with published
      evidence by surveying thoracic units nationally and performing a meta-analysis of
      current best evidence. METHODS: We systematically searched MEDLINE, EMBASE and
      CENTRAL for RCTs, comparing outcomes with and without application of suction to
      chest drains after lung surgery. A meta-analysis was performed using RevMan((c))
      software. A questionnaire concerning chest drain management and suction use was
      emailed to a clinical representative in every thoracic unit. RESULTS: Eight RCTs,
      published 2001-13, with 31-500 participants, were suitable for meta-analysis.
      Suction prolonged length of stay (weighted mean difference [WMD] 1.74 days; 95%
      confidence interval [CI] 1.17-2.30), chest tube duration (WMD 1.77 days; 95% CI
      1.47-2.07) and air leak duration (WMD 1.47 days; 95% CI 1.45-2.03). There was no
      difference in occurrence of prolonged air leak. Suction was associated with fewer
      instances of postoperative pneumothorax. Twenty-five of 39 thoracic units
      responded to the national survey. Suction is routinely used by all surgeons in 11
      units, not by any surgeon in 5 and by some surgeons in 9. Of the 91 surgeons
      represented, 62 (68%) routinely used suction. Electronic drains are used in 15
      units, 10 of which use them routinely. CONCLUSIONS: Application of suction to
      chest drains following non-pneumonectomy lung resection is common practice.
      Suction has an effect in hastening the removal of air and fluid in clinical
      experience but a policy of suction after lung resection has not been shown to
      offer improved clinical outcomes. Clinical practice is not aligned with Level 1a
      evidence.

PMID- 25870220
TI  - Early and late outcomes of complex aortic root surgery in patients with aortic
      root abscesses.
AB  - OBJECTIVES: To evaluate the early and long-term outcomes in patients undergoing
      complex aortic root reconstructions for complicated aortic root abscesses.
      METHODS: A total of 1199 patients underwent aortic valve surgery for aortic valve
      endocarditis between July 1999 and June 2012. Of these, 150 patients, who
      underwent complex isolated aortic root operations for aortic root abscesses, were
      included in this study. Radical resection of the abscess was performed in all
      patients followed by an aortic root replacement (ARR) in 91 (61.7%) or an aortic
      valve replacement with patch reconstruction of the aortic root in 59 (39.3%)
      patients. Prosthetic valve endocarditis was observed in 74 patients (49.3%).
      Logistic regression analysis identified the predictors of 30-day mortality.
      Estimated mean follow-up was 7.0 +/- 0.5 years (range 0-12.6 years). RESULTS:
      Mean age was 62 +/- 15 years and 87% (n = 130) were male. The majority of
      patients (91%; n = 137) underwent urgent or emergent surgery. Overall 30-day
      mortality was 19% (n = 29; ARR 21%; AVR 17%; P = 0.4). Postoperative low cardiac
      output, stroke and dialysis developed in 10.7, 4.7 and 25.3% of patients,
      respectively. Sepsis was the only independent predictor of 30-day mortality (odds
      ratio: 2.8; 95% confidence interval: 1.1-7.3; P = 0.03). The 1-, 5- and 10-year
      survival was 66 +/- 5, 54 +/- 5 and 51 +/- 6%, respectively. Overall, 9% of
      surviving patients required a reoperation for recurrent endocarditis resulting in
      a 1-, 5- and 10-year freedom from reoperation of 93 +/- 2, 91 +/- 3 and 85 +/-
      5%, respectively, which was not influenced by surgical technique used (ARR vs AVR
      with patch reconstruction; log rank P = 0.9). CONCLUSIONS: The surgical treatment
      of aortic root abscess is a challenging operation and is associated with a high
      early morbidity and mortality. However, the long-term survival and freedom from
      reoperation is satisfactory.

PMID- 25870221
TI  - Is limited surgery recommended if nodal involvement cannot be ruled out?

PMID- 25870222
TI  - Reply to Baisi et al.

PMID- 25870223
TI  - Pectoral muscle attenuation as a marker for breast cancer risk in full-field
      digital mammography.
AB  - BACKGROUND: Mammographic percent density is an established marker of breast
      cancer risk. In a study of screen film mammograms, we recently reported a novel
      feature from the pectoral muscle region to be associated with breast cancer risk
      independently of area percent density (APD). We now investigate whether our novel
      feature is associated with risk in a study based on full-field digital
      mammography (FFDM). METHODS: We carried out a breast cancer risk analysis using a
      data set of 3,552 healthy controls and 278 cases. We included three image-based
      measures in our analyses: volumetric percent density (VPD), APD, and the mean
      intensity of the pectoral muscle (MIP). The datasets comprised different machine
      vendors and models. In addition, the controls dataset was used to test for the
      association of our measures against rs10995190, in the ZNF365 gene, a genetic
      variant known to be associated with mammography density and breast cancer risk.
      RESULTS: MIP was associated with breast cancer risk [per SD OR, 0.811; 95%
      confidence interval (CI), 0.707-0.930; P = 0.0028] after adjusting for
      conventional covariates and VPD. It was also associated with the genetic variant
      rs10995190 after adjusting for VPD and other covariates (per allele effect =
      0.111; 95% CI, 0.053-0.170; P = 1.8 * 10(-4)). Results were similar when
      adjusting for APD instead of VPD. CONCLUSION: MIP is a novel mammographic marker,
      which is associated with breast cancer risk and the genetic variant rs10995190
      independently of PD measures. IMPACT: Inclusion of MIP in risk models should be
      considered for studies using PD from FFDM.

PMID- 25870224
TI  - The role of CD1d-restricted NKT cells in the clearance of Pseudomonas aeruginosa
      from the lung is dependent on the host genetic background.
AB  - Pseudomonas aeruginosa is an important human opportunistic pathogen, accounting
      for a significant fraction of hospital-acquired lung infections. CD1d-restricted
      NKT cells comprise an unusual innate-like T cell subset that plays important
      roles in both bacterial and viral infections. Previous reports have differed in
      their conclusions regarding the role of NKT cells in clearance of P. aeruginosa
      from the lung. Since there is significant strain-dependent variation in NKT cell
      number and function among different inbred strains of mice, we investigated
      whether the role of NKT cells was dependent on the host genetic background. We
      found that NKT cells did indeed play a critical role in the clearance of P.
      aeruginosa from the lungs of BALB/c mice but that they played no discernible role
      in clearance from the lungs of C57BL/6 mice. We found that the strain-dependent
      role of NKT cells was associated with significant strain-dependent differences in
      cytokine production by lung NKT cells and that impaired clearance of P.
      aeruginosa in BALB/c CD1d(-/-) mice was associated with an increase in neutrophil
      influx to the lung and increased levels of proinflammatory cytokines and
      chemokines after infection. Finally, we found that the role of alveolar
      macrophages was also dependent on the genetic background. These data provide
      further support for a model in which the unusually high level of variability in
      NKT cell number and function among different genetic backgrounds may be an
      important contributor to infectious-disease susceptibility and pathology.

PMID- 25870225
TI  - Intrauterine infection with plasmid-free Chlamydia muridarum reveals a critical
      role of the plasmid in chlamydial ascension and establishes a model for
      evaluating plasmid-independent pathogenicity.
AB  - Intravaginal infection with plasmid-competent but not plasmid-free Chlamydia
      muridarum induces hydrosalpinx in mouse upper genital tract, indicating a
      critical role of the plasmid in chlamydial pathogenicity. To evaluate the
      contribution of the plasmid to chlamydial ascension and activation of tubal
      inflammation, we delivered plasmid-free C. muridarum directly into the
      endometrium by intrauterine inoculation. We found that three of the six mouse
      strains tested, including CBA/J, C3H/HeJ, and C57BL/6J, developed significant
      hydrosalpinges when 1 * 10(7) inclusion-forming units (IFU) of plasmid-free C.
      muridarum were intrauterinally inoculated. Even when the inoculum was reduced to
      1 * 10(4) IFU, the CBA/J mice still developed robust hydrosalpinx. The
      hydrosalpinx development in CBA/J mice correlated with increased organism
      ascension to the oviduct following the intrauterine inoculation. The CBA/J mice
      intravaginally infected with the same plasmid-free C. muridarum strain displayed
      reduced ascending infection and failed to develop hydrosalpinx. These
      observations have demonstrated a critical role of the plasmid in chlamydial
      ascending infection. The intrauterine inoculation of the CBA/J mice with plasmid
      free C. muridarum not only resulted in more infection in the oviduct but also
      stimulated more inflammatory infiltration and cytokine production in the oviduct
      than the intravaginal inoculation, suggesting that the oviduct inflammation can
      be induced by plasmid-independent factors, which makes the hydrosalpinx induction
      in CBA/J mice by intrauterine infection with plasmid-free C. muridarum a suitable
      model for investigating plasmid-independent pathogenic mechanisms.

PMID- 25870226
TI  - A CLAG3 mutation in an amphipathic transmembrane domain alters malaria parasite
      nutrient channels and confers leupeptin resistance.
AB  - Erythrocytes infected with malaria parasites have increased permeability to ions
      and nutrients, as mediated by the plasmodial surface anion channel (PSAC) and
      recently linked to parasite clag3 genes. Although the encoded protein is integral
      to the host membrane, its precise contribution to solute transport remains
      unclear because it lacks conventional transmembrane domains and does not have
      homology to ion channel proteins in other organisms. Here, we identified a
      probable CLAG3 transmembrane domain adjacent to a variant extracellular motif.
      Helical-wheel analysis revealed strict segregation of polar and hydrophobic
      residues to opposite faces of a predicted alpha-helical transmembrane domain,
      suggesting that the domain lines a water-filled pore. A single CLAG3 mutation
      (A1210T) in a leupeptin-resistant PSAC mutant falls within this transmembrane
      domain and may affect pore structure. Allelic-exchange transfection and site
      directed mutagenesis revealed that this mutation alters solute selectivity in the
      channel. The A1210T mutation also reduces the blocking affinity of PSAC
      inhibitors that bind on opposite channel faces, consistent with global changes in
      channel structure. Transfected parasites carrying this mutation survived a
      leupeptin challenge significantly better than a transfection control did. Thus,
      the A1210T mutation contributes directly to both altered PSAC activity and
      leupeptin resistance. These findings reveal the molecular basis of a novel
      antimalarial drug resistance mechanism, provide a framework for determining the
      channel's composition and structure, and should guide the development of
      therapies targeting the PSAC.

PMID- 25870227
TI  - Variation in Plasmodium falciparum erythrocyte invasion phenotypes and merozoite
      ligand gene expression across different populations in areas of malaria
      endemicity.
AB  - Plasmodium falciparum merozoites use diverse alternative erythrocyte receptors
      for invasion and variably express cognate ligands encoded by the erythrocyte
      binding antigen (eba) and reticulocyte binding-like homologue (Rh) gene families.
      Previous analyses conducted on parasites from single populations in areas of
      endemicity revealed a wide spectrum of invasion phenotypes and expression
      profiles, although comparisons across studies have been limited by the use of
      different protocols. For direct comparisons within and among populations,
      clinical isolates from three different West African sites of endemicity (in
      Ghana, Guinea, and Senegal) were cryopreserved and cultured ex vivo after thawing
      in a single laboratory to assay invasion of target erythrocytes pretreated with
      enzymes affecting receptor subsets. Complete invasion assay data from 67 isolates
      showed no differences among the populations in the broad range of phenotypes
      measured by neuraminidase treatment (overall mean, 40.6% inhibition) or trypsin
      treatment (overall mean, 83.3% inhibition). The effects of chymotrypsin treatment
      (overall mean, 79.2% inhibition) showed heterogeneity across populations
      (Kruskall-Wallis P = 0.023), although the full phenotypic range was seen in each.
      Schizont-stage transcript data for a panel of 8 invasion ligand genes (eba175,
      eba140, eba181, Rh1, Rh2a, Rh2b, Rh4, and Rh5) were obtained for 37 isolates,
      showing similar ranges of variation in each population except that eba175 levels
      tended to be higher in parasites from Ghana than in those from Senegal (whereas
      levels of eba181 and Rh2b were lower in parasites from Ghana). The broad
      diversity in invasion phenotypes and gene expression seen within each local
      population, with minimal differences among them, is consistent with a hypothesis
      of immune selection maintaining parasite variation.

PMID- 25870228
TI  - Novel Aggregation Properties of Candida albicans Secreted Aspartyl Proteinase
      Sap6 Mediate Virulence in Oral Candidiasis.
AB  - Candida albicans, a commensal fungus of the oral microbiome, causes oral
      candidiasis in humans with localized or systemic immune deficiencies. Secreted
      aspartic proteinases (Saps) are a family of 10 related proteases and are
      virulence factors due to their proteolytic activity, as well as their roles in
      adherence and colonization of host tissues. We found that mice infected
      sublingually with C. albicans cells overexpressing Sap6 (SAP6 OE and a Deltasap8
      strain) had thicker fungal plaques and more severe oral infection, while
      infection with the Deltasap6 strain was attenuated. These hypervirulent strains
      had highly aggregative colony structure in vitro and higher secreted proteinase
      activity; however, the levels of proteinase activity of C. albicans Saps did not
      uniformly match their abilities to damage cultured oral epithelial cells (SCC-15
      cells). Hyphal induction in cells overexpressing Sap6 (SAP6 OE and Deltasap8
      cells) resulted in formation of large cell-cell aggregates. These aggregates
      could be produced in germinated wild-type cells by addition of native or heat
      inactivated Sap6. Sap6 bound only to germinated cells and increased C. albicans
      adhesion to oral epithelial cells. The adhesion properties of Sap6 were lost upon
      deletion of its integrin-binding motif (RGD) and could be inhibited by addition
      of RGD peptide or anti-integrin antibodies. Thus, Sap6 (but not Sap5) has an
      alternative novel function in cell-cell aggregation, independent of its
      proteinase activity, to promote infection and virulence in oral candidiasis.

PMID- 25870229
TI  - Phenotypic Heterogeneity in Expression of the K1 Polysaccharide Capsule of
      Uropathogenic Escherichia coli and Downregulation of the Capsule Genes during
      Growth in Urine.
AB  - Uropathogenic Escherichia coli (UPEC) is the major causative agent of
      uncomplicated urinary tract infections (UTI). The K1 capsule on the surface of
      UPEC strains is a key virulence factor, and its expression may be important in
      the onset and progression of UTI. In order to understand capsule expression in
      more detail, we analyzed its expression in the UPEC strain UTI89 during growth in
      rich medium (LB medium) and urine and during infection of a bladder epithelial
      cell line. Comparison of capsule gene transcription using a chromosomal gfp
      reporter fusion showed a significant reduction in transcription during growth in
      urine compared to that during growth in LB medium. When examined at the single
      cell level, following growth in both media, capsule gene expression appears to be
      heterogeneous, with two distinct green fluorescent protein (GFP)-expressing
      populations. Using anti-K1 antibody, we showed that this heterogeneity in gene
      expression results in two populations of encapsulated and unencapsulated cells.
      We demonstrated that the capsule hinders attachment to and invasion of epithelial
      cells and that the unencapsulated cells within the population preferentially
      adhere to and invade bladder epithelial cells. We found that once internalized,
      UTI89 starts to produce capsule to aid in its intracellular survival and spread.
      We propose that this observed phenotypic diversity in capsule expression is a
      fitness strategy used by the bacterium to deal with the constantly changing
      environment of the urinary tract. 

PMID- 25870230
TI  - Macrophage Polarization during Murine Lyme Borreliosis.
AB  - Infection of C3H mice with Borrelia burgdorferi, the causative agent of Lyme
      disease, reliably produces an infectious arthritis and carditis that peak around
      3 weeks postinfection and then spontaneously resolve. Macrophage polarization has
      been suggested to drive inflammation, the clearance of bacteria, and tissue
      repair and resolution in a variety of infectious disease models. During Lyme
      disease it is clear that macrophages are capable of clearing Borrelia spirochetes
      and exhausted neutrophils; however, the role of macrophage phenotype in disease
      development or resolution has not been studied. Using classical (NOS2) and
      alternative (CD206) macrophage subset-specific markers, we determined the
      phenotype of F4/80(+) macrophages within the joints and heart throughout the
      infection time course. Within the joint, CD206(+) macrophages dominated
      throughout the course of infection, and NOS2(+) macrophage numbers became
      elevated only during the peak of inflammation. We also found dual NOS2(+)
      CD206(+) macrophages which increased during resolution. In contrast to findings
      for the ankle joints, numbers of NOS2(+) and CD206(+) macrophages in the heart
      were similar at the peak of inflammation. 5-Lipoxygenase-deficient (5-LOX(-/-))
      mice, which display a failure of Lyme arthritis resolution, recruited fewer
      F4/80(+) cells to the infected joints and heart, but macrophage subset
      populations were unchanged. These results highlight differences in the
      inflammatory infiltrates during Lyme arthritis and carditis and demonstrate the
      coexistence of multiple macrophage subsets within a single inflammatory site. 

PMID- 25870232
TI  - Tregs strip dendritic cells of CD70 to regulate Th1 differentiation.

PMID- 25870231
TI  - The Type VI Secretion System Modulates Flagellar Gene Expression and Secretion in
      Citrobacter freundii and Contributes to Adhesion and Cytotoxicity to Host Cells.
AB  - The type VI secretion system (T6SS) as a virulence factor-releasing system
      contributes to virulence development of various pathogens and is often activated
      upon contact with target cells. Citrobacter freundii strain CF74 has a complete
      T6SS genomic island (GI) that contains clpV, hcp-2, and vgr T6SS genes. We
      constructed clpV, hcp-2, vgr, and T6SS GI deletion mutants in CF74 and analyzed
      their effects on the transcriptome overall and, specifically, on the flagellar
      system at the levels of transcription and translation. Deletion of the T6SS GI
      affected the transcription of 84 genes, with 15 and 69 genes exhibiting higher
      and lower levels of transcription, respectively. Members of the cell motility
      class of downregulated genes of the CF74DeltaT6SS mutant were mainly flagellar
      genes, including effector proteins, chaperones, and regulators. Moreover, the
      production and secretion of FliC were also decreased in clpV, hcp-2, vgr, or T6SS
      GI deletion mutants in CF74 and were restored upon complementation. In swimming
      motility assays, the mutant strains were found to be less motile than the wild
      type, and motility was restored by complementation. The mutant strains were
      defective in adhesion to HEp-2 cells and were restored partially upon
      complementation. Further, the CF74DeltaT6SS, CF74DeltaclpV, and CF74Deltahcp-2
      mutants induced lower cytotoxicity to HEp-2 cells than the wild type. These
      results suggested that the T6SS GI in CF74 regulates the flagellar system,
      enhances motility, is involved in adherence to host cells, and induces
      cytotoxicity to host cells. Thus, the T6SS plays a wide-ranging role in C.
      freundii. 

PMID- 25870233
TI  - The Behavioral Relevance of Task Information in Human Prefrontal Cortex.
AB  - Human lateral prefrontal cortex (LPFC) is thought to play a critical role in
      enabling cognitive flexibility, particularly when performing novel tasks.
      However, it remains to be established whether LPFC representation of task
      relevant information in such situations actually contributes to successful
      performance. We utilized pattern classification analyses of functional MRI
      activity to identify novelty-sensitive brain regions as participants rapidly
      switched between performance of 64 complex tasks, 60 of which were novel. In
      three of these novelty-sensitive regions-located within distinct areas of left
      anterior LPFC-trial-evoked activity patterns discriminated correct from error
      trials. Further, these regions also contained information regarding the task
      relevant decision rule, but only for successfully performed trials. This suggests
      that left anterior LPFC may be particularly important for representing task
      information that contributes to the cognitive flexibility needed to perform
      successfully in novel task situations.

PMID- 25870234
TI  - A call for transparency in tracking student and postdoc career outcomes.
AB  - There is a common misconception that the United States is suffering from a "STEM
      shortage," a dearth of graduates with scientific, technological, engineering, and
      mathematical backgrounds. In biomedical science, however, we are likely suffering
      from the opposite problem and could certainly better tailor training to actual
      career outcomes. At the Future of Research Symposium, various workshops
      identified this as a key issue in a pipeline traditionally geared toward
      academia. Proposals for reform all ultimately come up against the same problem:
      there is a shocking lack of data at institutional and national levels on the
      size, shape, and successful careers of participants in the research workforce. In
      this paper, we call for improved institutional reporting of the number of
      graduate students and postdocs and their training and career outcomes. 

PMID- 25870235
TI  - Homozygous NOTCH3 null mutation and impaired NOTCH3 signaling in recessive early
      onset arteriopathy and cavitating leukoencephalopathy.
AB  - Notch signaling is essential for vascular physiology. Neomorphic heterozygous
      mutations in NOTCH3, one of the four human NOTCH receptors, cause cerebral
      autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy
      (CADASIL). Hypomorphic heterozygous alleles have been occasionally described in
      association with a spectrum of cerebrovascular phenotypes overlapping CADASIL,
      but their pathogenic potential is unclear. We describe a patient with childhood
      onset arteriopathy, cavitating leukoencephalopathy with cerebral white matter
      abnormalities presented as diffuse cavitations, multiple lacunar infarctions and
      disseminated microbleeds. We identified a novel homozygous c.C2898A (p.C966*)
      null mutation in NOTCH3 abolishing NOTCH3 expression and causing NOTCH3 signaling
      impairment. NOTCH3 targets acting in the regulation of arterial tone (KCNA5) or
      expressed in the vasculature (CDH6) were downregulated. Patient's vessels were
      characterized by smooth muscle degeneration as in CADASIL, but without deposition
      of granular osmiophilic material (GOM), the CADASIL hallmark. The heterozygous
      parents displayed similar but less dramatic trends in decrease in the expression
      of NOTCH3 and its targets, as well as in vessel degeneration. This study suggests
      a functional link between NOTCH3 deficiency and pathogenesis of vascular
      leukoencephalopathies. 

PMID- 25870236
TI  - MPP8 and SIRT1 crosstalk in E-cadherin gene silencing and epithelial-mesenchymal
      transition.
AB  - As a critical developmental process, epithelial-mesenchymal transition (EMT)
      involves complex transcriptional reprogramming and has been closely linked to
      malignant progression. Although various epigenetic modifications, such as histone
      deacetylation and H3K9 methylation, have been implicated in this process, how
      they are coordinated remains elusive. We recently revealed that MPP8 couples H3K9
      methylation and DNA methylation for E-cadherin gene silencing and promotes tumor
      cell migration, invasion, and EMT. Here, we show that MPP8 cooperates with the
      class III HDAC SIRT1 in this process through their physical interaction. SIRT1
      antagonizes PCAF-catalyzed MPP8-K439 acetylation to protect MPP8 from ubiquitin
      proteasome-mediated proteolysis. Conversely, MPP8 recruits SIRT1 for H4K16
      deacetylation after binding to methyl-H3K9 on target promoters. Consequently,
      disabling either MPP8 methyl-H3K9 binding or SIRT1 interaction de-represses E
      cadherin and reduces EMT phenotypes, as does knockdown of MPP8 or SIRT1 in
      prostate cancer cells. These results illustrate how SIRT1 and MPP8 reciprocally
      promote each other's function and coordinate epithelial gene silencing and EMT. 

PMID- 25870237
TI  - Recycled IL-7 Can Be Delivered to Neighboring T Cells.
AB  - IL-7 is a key homeostatic cytokine that provides signals for T cell survival and
      proliferation in vivo. In this article, we provide evidence that IL-7 utilization
      is enhanced by a novel mechanism of cytokine "recycling" during which T cells
      treated with rIL-7 are rapidly induced to express p-STAT5 and are subsequently
      able to recycle biologically active cytokine for release to neighboring cells in
      soluble form. Our observations indicate that the ability of cells to recycle IL-7
      is dependent on IL-7R alpha-chain (CD127) and endocytosis, consistent with a
      model whereby IL-7 is internalized via receptor interactions before recycling.
      These observations provide evidence of a novel mechanism that enables cells to
      optimally use IL-7. 

PMID- 25870238
TI  - MF59 Mediates Its B Cell Adjuvanticity by Promoting T Follicular Helper Cells and
      Thus Germinal Center Responses in Adult and Early Life.
AB  - The early life influenza disease burden calls for more effective vaccines to
      protect this vulnerable population. Influenza vaccines including the MF59 oil-in
      water adjuvant induce higher, broader, and more persistent Ab responses in adults
      and particularly in young, through yet undefined mechanisms. In this study, we
      show that MF59 enhances adult murine IgG responses to influenza hemagglutinin
      (HA) by promoting a potent T follicular helper cells (TFH) response, which
      directly controls the magnitude of the germinal center (GC) B cell response.
      Remarkably, this enhancement of TFH and GC B cells is already fully functional in
      3-wk-old infant mice, which were fully protected by HA/MF59 but not HA/PBS
      immunization against intranasal challenge with the homologous H1N1
      (A/California/7/2009) strain. In 1-wk-old neonatal mice, MF59 recruits and
      activates APCs, efficiently induces CD4(+) effector T cells and primes for
      enhanced infant responses but induces few fully functional TFH cells, which are
      mostly follicular regulatory T cells, and poor GC and anti-HA responses. The B
      cell adjuvanticity of MF59 appears to be mediated by the potent induction of TFH
      cells which directly controls GC responses both in adult and early life, calling
      for studies assessing its capacity to enhance the efficacy of influenza
      immunization in young infants. 

PMID- 25870239
TI  - The Rho GTPase Cdc42 Is Essential for the Activation and Function of Mature B
      Cells.
AB  - The Rho GTPase Cdc42 coordinates regulation of the actin and the microtubule
      cytoskeleton by binding and activating the Wiskott-Aldrich syndrome protein. We
      sought to define the role of intrinsic expression of Cdc42 by mature B cells in
      their activation and function. Mice with inducible deletion of Cdc42 in mature B
      cells formed smaller germinal centers and had a reduced Ab response, mostly of
      low affinity to T cell-dependent Ag, compared with wild-type (WT) controls.
      Spreading formation of long protrusions that contain F-actin, microtubules, and
      Cdc42-interacting protein 4, and assumption of a dendritic cell morphology in
      response to anti-CD40 plus IL-4 were impaired in Cdc42-deficient B cells compared
      with WT B cells. Cdc42-deficient B cells had an intact migratory response to
      chemokine in vitro, but their homing to the B cell follicles in the spleen in
      vivo was significantly impaired. Cdc42-deficient B cells induced a skewed
      cytokine response in CD4(+) T cells, compared with WT B cells. Our results
      demonstrate a critical role for Cdc42 in the motility of mature B cells, their
      cognate interaction with T cells, and their differentiation into Ab-producing
      cells. 

PMID- 25870240
TI  - Aminoacyl tRNA Synthetase-Interacting Multifunctional Protein 1 Acts as a Novel B
      Cell-Activating Factor In Vitro and In Vivo.
AB  - Endogenous B cell-activating factors play pivotal roles in defense mechanisms by
      regulating B cell responses. We previously reported that aminoacyl tRNA
      synthetase-interacting multifunctional protein 1 (AIMP1) functions as a novel
      proinflammatory cytokine that activates macrophages and dendritic cells. However,
      roles of AIMP1 in B cell responses have not been studied. In this study, we
      investigated the effects of AIMP1 on B cell responses and their underlying
      mechanisms. AIMP1 induced the expression of surface activation markers on murine
      B cells and the proliferation of B cells. Additionally, AIMP1 increased the
      expression of activation-induced deaminase and class switch recombination in B
      cells. AIMP1 also had synergistic effects on B cell activation when combined with
      CD40 stimulus. Intracellular signaling experiments showed that AIMP1 activated B
      cells through a protein kinase C/NF-kappaB signaling pathway. Importantly, i.v.
      injection of AIMP1 into mice increased the expression of CD69 on splenic B cells
      and significantly enhanced Ag-specific Ab production. Taken together, our results
      show that AIMP1 acts as a novel B cell-activating factor. AIMP1-mediated B cell
      activation and the involvement of AIMP1 in diseases will provide additional
      information for therapeutic strategies. 

PMID- 25870241
TI  - High-density lipoprotein attenuates Th1 and th17 autoimmune responses by
      modulating dendritic cell maturation and function.
AB  - Aberrant levels and function of the potent anti-inflammatory high-density
      lipoprotein (HDL) and accelerated atherosclerosis have been reported in patients
      with autoimmune inflammatory diseases. Whether HDL affects the development of an
      autoimmune response remains elusive. In this study, we used apolipoprotein A-I
      deficient (apoA-I(-/-)) mice, characterized by diminished circulating HDL levels,
      to delineate the role of HDL in autoimmunity. ApoA-I(-/-) mice exhibited
      increased severity of Ag-induced arthritis compared with wild-type mice, and this
      was associated with elevated Th1 and Th17 cell reactivity in the draining lymph
      nodes. Furthermore, reconstituted HDL (rHDL) attenuated IFN-gamma and IL-17
      secretion by Ag-specific T cells upon stimulation of draining lymph nodes in
      vitro. The suppressive effects of rHDL were mediated through modulation of
      dendritic cell (DC) function. Specifically, rHDL-treated DCs demonstrated an
      immature phenotype characterized by downregulated costimulatory molecules, the
      release of low amounts of proinflammatory cytokines, and failure to promote T
      cell proliferation in vitro. The mechanism of action involved the inhibition of
      NF-kappaB nuclear translocation and the decrease of Myd88 mRNA levels by rHDL.
      Finally, modulation of DC function by rHDL was critically dependent on the
      presence of scavenger receptor class B type I and ATP Binding Cassette
      Transporter A1, but not the ATP Binding Cassette Transporter G1. These findings
      reveal a novel role of HDL in the regulation of adaptive inflammatory responses
      through suppression of DC function that could be exploited therapeutically in
      autoimmune inflammatory diseases. 

PMID- 25870242
TI  - Ex vivo and in vitro effect of serum amyloid a in the induction of macrophage M2
      markers and efferocytosis of apoptotic neutrophils.
AB  - Macrophages affect the magnitude and duration of inflammatory response in a
      functionally heterogeneous manner. The phenotype of macrophages is maintained
      through a reversible homeostatic mechanism. A number of determinants that
      modulate macrophage plasticity have been identified, although the precise
      mechanisms are not fully understood. In this study, we report that stimulation of
      isolated human blood monocytes and mouse bone marrow-derived macrophages with
      human serum amyloid A (SAA), a major acute-phase protein, leads to induced
      expression of macrophage M2 markers, including IL-10, Ym1, Fizz-1, MRC1, IL-1Rn,
      and CCL17. The same effect was observed with macrophages exposed to SAA in
      peritoneal cavity. SAA also increases arginase 1 activity and enhances macrophage
      efferocytosis of apoptotic neutrophils in mouse macrophages. The induction of M2
      markers requires MyD88 and the activation of multiple signaling pathways, but it
      is independent of Stat6. SAA induces IFN regulatory factor (IRF)4 expression and
      increases its DNA-binding activity. Silencing IRF4 by small interfering RNA
      abrogates SAA-induced expression of the M2 markers. These results suggest a
      potential role for SAA to alter macrophage phenotype and modulate macrophage
      functions through an MyD88-dependent mechanism that involves IRF4-mediated
      transcription. 

PMID- 25870243
TI  - IL-33 Reverses an Obesity-Induced Deficit in Visceral Adipose Tissue ST2+ T
      Regulatory Cells and Ameliorates Adipose Tissue Inflammation and Insulin
      Resistance.
AB  - Obesity is associated with insulin resistance and inflammation thought to be
      caused by a visceral adipose tissue (VAT)-localized reduction in immunoregulatory
      cells and increase in proinflammatory immune cells. We previously found that VAT
      regulatory T cells (Tregs) normally express high levels of IL-10 and that
      expression of this cytokine in VAT Tregs is specifically reduced in mice fed a
      high-fat diet. In this study, we further investigated the phenotype of VAT Tregs
      and found that the majority of IL-10-expressing Tregs in the VAT of lean mice
      also expressed the ST2 chain of the IL-33R. In addition to high expression of IL
      10, ST2(+) Tregs in lean VAT expressed higher proportions of Th2-associated
      proteins, including GATA3 and CCR4, and Neuropillin-1 compared with ST2(-) Tregs.
      The proportion of ST2(+) Tregs in VAT was severely diminished in obese mice that
      had been fed a high-fat/sucrose diet, and this effect could be completely
      reversed by treatment with IL-33. IL-33 treatment also reversed VAT inflammation
      in obese mice and resulted in a reduction of hyperinsulinemia and insulin
      resistance. These data suggest that IL-33 contributes to the maintenance of the
      normal pool of ST2(+) Tregs in the VAT, and that therapeutic administration of IL
      33 results in multiple anti-obesity effects, including the reversal of VAT
      inflammation and alleviation of insulin resistance. 

PMID- 25870244
TI  - Young, proliferative thymic epithelial cells engraft and function in aging
      thymuses.
AB  - The thymus reaches its maximum size early in life and then begins to shrink,
      producing fewer T cells with increasing age. This thymic decline is thought to
      contribute to age-related T cell lymphopenias and hinder T cell recovery after
      bone marrow transplantation. Although several cellular and molecular processes
      have been implicated in age-related thymic involution, their relative
      contributions are not known. Using heterochronic parabiosis, we observe that
      young circulating factors are not sufficient to drive regeneration of the aged
      thymus. In contrast, we find that resupplying young, engraftable thymic
      epithelial cells (TECs) to a middle-aged or defective thymus leads to thymic
      growth and increased T cell production. Intrathymic transplantation and in vitro
      colony-forming assays reveal that the engraftment and proliferative capacities of
      TECs diminish early in life, whereas the receptivity of the thymus to TEC
      engraftment remains relatively constant with age. These results support a model
      in which thymic growth and subsequent involution are driven by cell-intrinsic
      changes in the proliferative capacity of TECs, and further show that young TECs
      can engraft and directly drive the growth of involuted thymuses. 

PMID- 25870245
TI  - Histamine promotes the development of monocyte-derived dendritic cells and
      reduces tumor growth by targeting the myeloid NADPH oxidase.
AB  - The efficiency of immune-mediated clearance of cancer cells is hampered by
      immunosuppressive mediators in the malignant microenvironment, including NADPH
      oxidase-derived reactive oxygen species. We aimed at defining the effects of
      histamine, an inhibitor of the myeloid NADPH oxidase/NOX2, on the development of
      Ag-presenting dendritic cells (DCs) from myeloid precursors and the impact of
      these mechanisms for tumor growth. Histamine was found to promote the maturation
      of human DCs from monocytes by increasing the expression of HLA-DR and
      costimulatory molecules, which resulted in improved induction of Th cells with
      Th0 polarity. Experiments using wild-type and NOX2-deficient myelomonoblastic
      cells showed that histamine facilitated myeloid cell maturation only in cells
      capable of generating reactive oxygen species. Treatment of mice with histamine
      reduced the growth of murine EL-4 lymphomas in parallel with an increment of
      tumor-infiltrating DCs in NOX2-sufficient mice but not in NOX2-deficient
      (gp91(phox) (-/-)) mice. We propose that strategies to target the myeloid NADPH
      oxidase may facilitate the development of endogenous DCs in cancer. 

PMID- 25870246
TI  - Cancer-Associated Oxidase ERO1-alpha Regulates the Expression of MHC Class I
      Molecule via Oxidative Folding.
AB  - ERO1-alpha is an oxidizing enzyme that exists in the endoplasmic reticulum and is
      induced under hypoxia. It reoxidizes the reduced form of protein disulfide
      isomerase that has oxidized target proteins. We found that ERO1-alpha is
      overexpressed in a variety of tumor types. MHC class I H chain (HC) has two
      disulfide bonds in the alpha2 and alpha3 domains. MHC class I HC folding is
      linked to the assembly of MHC class I molecules because only fully disulfide
      bonded class I HCs efficiently assemble with beta2-microglobulin. In this study,
      we show that ERO1-alpha associates with protein disulfide isomerase, calnexin,
      and immature MHC class I before being incorporated into the TAP-1-associated
      peptide-loading complex. Importantly, ERO1-alpha regulates the redox state as
      well as cell surface expression of MHC class I, leading to alteration of
      susceptibility by CD8(+) T cells. Similarly, the ERO1-alpha expression within
      cancer cells was associated with the expression level of MHC class I in colon
      cancer tissues. Thus, the cancer-associated ERO1-alpha regulates the expression
      of the MHC class I molecule via oxidative folding. 

PMID- 25870247
TI  - In Vitro and In Vivo Analysis of the Gram-Negative Bacteria-Derived Riboflavin
      Precursor Derivatives Activating Mouse MAIT Cells.
AB  - Mucosal-associated invariant T (MAIT) cells recognize microbial compounds
      presented by the MHC-related 1 (MR1) protein. Although riboflavin precursor
      derivatives from Gram-positive bacteria have been characterized, some level of
      ligand heterogeneity has been suggested through the analysis of the MAIT cell TCR
      repertoire in humans and differential reactivity of human MAIT cell clones
      according to the bacteria. In this study, using Gram-negative bacteria mutated
      for the riboflavin biosynthetic pathway, we show a strict correlation between the
      ability to synthesize the 5-amino-ribityl-uracil riboflavin precursor and to
      activate polyclonal and quasi-monoclonal mouse MAIT cells. To our knowledge, we
      show for the first time that the semipurified bacterial fraction and the
      synthetic ligand activate murine MAIT cells in vitro and in vivo. We describe new
      MR1 ligands that do not activate MAIT cells but compete with bacterial and
      synthetic compounds activating MAIT cells, providing the capacity to modulate
      MAIT cell activation. Through competition experiments, we show that the most
      active synthetic MAIT cell ligand displays the same functional avidity for MR1 as
      does the microbial compound. Altogether, these results show that most, if not
      all, MAIT cell ligands found in Escherichia coli are related to the riboflavin
      biosynthetic pathway and display very limited heterogeneity. 

PMID- 25870248
TI  - Defects of the Carney complex gene (PRKAR1A) in odontogenic tumors.
AB  - The surgical treatment of some odontogenic tumors often leads to tooth and
      maxillary bone loss as well as to facial deformity. Therefore, the identification
      of genes involved in the pathogenesis of odontogenic tumors may result in
      alternative molecular therapies. The PRKAR1A gene displays a loss of protein
      expression as well as somatic mutations in odontogenic myxomas, an odontogenic
      ectomesenchymal neoplasm. We used a combination of quantitative RT-PCR (qRT-PCR),
      immunohistochemistry, loss of heterozygosity (LOH) analysis, and direct
      sequencing of all PRKAR1A exons to assess if this gene is altered in mixed
      odontogenic tumors. Thirteen tumors were included in the study: six ameloblastic
      fibromas, four ameloblastic fibro-odontomas, one ameloblastic fibrodentinoma, and
      two ameloblastic fibrosarcomas. The epithelial components of the tumors were
      separated from the mesenchymal by laser microdissection in most of the cases. We
      also searched for odontogenic pathology in Prkar1a(+) (/) (-) mice. PRKAR1A
      mRNA/protein expression was decreased in the benign mixed odontogenic tumors in
      association with LOH at markers around the PRKAR1A gene. We also detected a
      missense and two synonymous mutations along with two 5'-UTR and four intronic
      mutations in mixed odontogenic tumors. Prkar1a(+) (/) (-) mice did not show
      evidence of odontogenic tumor formation, which indicates that additional genes
      may be involved in the pathogenesis of such tumors, at least in rodents. We
      conclude that the PRKAR1A gene and its locus are altered in mixed odontogenic
      tumors. PRKAR1A expression is decreased in a subset of tumors but not in all, and
      Prkar1a(+) (/) (-) mice do not show abnormalities, which indicates that
      additional genes play a role in this tumor's pathogenesis. 

PMID- 25870249
TI  - Regulation of vascular endothelial growth factor in prostate cancer.
AB  - Prostate cancer (PCa) is the most common malignancy affecting men in the western
      world. Although radical prostatectomy and radiation therapy can successfully
      treat PCa in the majority of patients, up to ~30% will experience local
      recurrence or metastatic disease. Prostate carcinogenesis and progression is
      typically an androgen-dependent process. For this reason, therapies for recurrent
      PCa target androgen biosynthesis and androgen receptor function. Such androgen
      deprivation therapies (ADT) are effective initially, but the duration of response
      is typically <=24 months. Although ADT and taxane-based chemotherapy have
      delivered survival benefits, metastatic PCa remains incurable. Therefore, it is
      essential to establish the cellular and molecular mechanisms that enable
      localized PCas to invade and disseminate. It has long been accepted that
      metastases require angiogenesis. In the present review, we examine the essential
      role for angiogenesis in PCa metastases, and we focus in particular on the
      current understanding of the regulation of vascular endothelial growth factor
      (VEGF) in localized and metastatic PCa. We highlight recent advances in
      understanding the role of VEGF in regulating the interaction of cancer cells with
      tumor-associated immune cells during the metastatic process of PCa. We summarize
      the established mechanisms of transcriptional and post-transcriptional regulation
      of VEGF in PCa cells and outline the molecular insights obtained from preclinical
      animal models of PCa. Finally, we summarize the current state of anti
      angiogenesis therapies for PCa and consider how existing therapies impact VEGF
      signaling.

PMID- 25870250
TI  - Body fatness as a cause of cancer: epidemiologic clues to biologic mechanisms.
AB  - Carrying excess body fat is a leading cause of cancer. Epidemiologic evidence
      gives strong clues about the mechanisms that link excess adiposity to risk for
      several cancer sites. For postmenopausal breast cancer and endometrial cancer,
      the hyper-estrogenic state that is induced by excess body fatness is the likely
      cause. For esophageal cancer and gallbladder cancer, chronic local inflammation
      induced by acid reflux and gallstones is the likely cause, and for liver cancer,
      local inflammation induced by hepatic fatty infiltration is the likely cause.
      However, for several other cancers known to be associated with excess adiposity,
      including cancers of the colon, pancreas, ovary, kidney, and prostate, specific
      causes are not known. Possible candidates include elevated systemic or local
      tissue inflammation induced by adiposity and effects of the elevated levels of
      leptin, insulin, IGFs, and depressed immune function that are seen with excess
      adiposity. There is growing evidence that intentional weight loss not only
      reduces circulating levels of cancer-associated factors but that it also reduces
      cancer incidence and recurrence. Better research is needed to understand the
      mechanisms that link excess body fat to cancer risk as well as to understand the
      amount of weight loss needed for substantial cancer risk reduction. Finally, as
      we develop better understanding of the mediators of the effects of excess body
      fatness on cancer risk, we should identify pharmacologic interventions that
      target those mediators so that they can be used to complement weight loss in
      order to reduce cancer risk. 

PMID- 25870251
TI  - Nuclear TAZ expression associates with the triple-negative phenotype in breast
      cancer.
AB  - The Hippo signaling pathway, a conserved regulator of organ size, has emerged as
      an important regulatory pathway in cancer. The final transducer effectors of this
      pathway in mammals are the oncoproteins TAZ and YAP1, which are transcriptional
      coactivators of target genes involved in cell proliferation and survival. TAZ has
      been previously reported to play a role in tumorigenesis in breast cancer, but
      detailed analyses of the different breast cancer phenotypes have not been
      conducted thus far. We analyzed TAZ expression by immunohistochemistry in a
      retrospective series of 640 invasive breast carcinomas, comprising
      estrogen/progesterone receptor-positive (ER+/PR+), HER2-positive, and triple
      negative (TN) tumors. We found a strong association of TAZ nuclear expression
      with the TN phenotype (60.5% TAZ-positive, P<0.001), which was strengthened when
      stratified into the basal-like subtype (70.8% TAZ-positive, P<0.001). Moreover,
      90% of metaplastic breast carcinomas with morphological epithelial-mesenchymal
      transition features were TAZ-positive. We also investigated whether amplification
      or differential DNA methylation of the TAZ-encoding locus could account for the
      observed enhanced TAZ protein expression in the TN/basal phenotype. Amplification
      of the TAZ locus was analyzed by fluorescence in situ hybridization in 30 TN
      tumors, and we found gene amplification in some cases (6.45%). DNA methylation
      analysis was performed using the Sequenom MassArray MALDI-TOF platform, and we
      observed similar low methylation levels both in TN (n=25) and ER+/PR+ (n=26)
      tumors. These results were further confirmed using a panel of breast cancer cell
      lines and using the TCGA dataset. Finally, patients with strong TAZ expression
      showed poorer clinical outcomes with respect to both recurrence and overall
      survival. 

PMID- 25870252
TI  - Tall cell papillary thyroid carcinoma: new diagnostic criteria and mutations in
      BRAF and TERT.
AB  - The tall cell (TC) variant of papillary thyroid carcinoma (PTC) has an
      unfavorable prognosis. The diagnostic criteria remain inconsistent, and the role
      of a minor TC component is unclear. Molecular diagnostic markers are not
      available; however, there are two potential candidates: BRAF V600E and telomerase
      reverse transcriptase (TERT) promoter mutations. Using a novel approach, we
      enriched a collective with PTCs that harbored an adverse outcome, which overcame
      the limited statistical power of most studies. This enabled us to review 125 PTC
      patients, 57 of which had an adverse outcome. The proportion of TCs that
      constituted a poor prognosis was assessed. All of the tumors underwent sequencing
      for TERT promoter and BRAF V600E mutational status and were stained with an
      antibody to detect the BRAF V600E mutation. A 10% cutoff for TCs was
      significantly associated with advanced tumor stage and lymph node metastasis.
      Multivariate analysis showed that TCs above 10% were the only significant factor
      for overall, tumor-specific, and relapse-free survival. Seven percent of the
      cases had a TERT promoter mutation, whereas 61% demonstrated a BRAF mutation. The
      presence of TC was significantly associated with TERT promoter and BRAF
      mutations. TERT predicted highly significant tumor relapse (P<0.001). PTCs
      comprised of at least 10% TCs are associated with an adverse clinical outcome and
      should be reported accordingly. BRAF did not influence patient outcome.
      Nevertheless, a positive status should encourage the search for TCs. TERT
      promoter mutations are a strong predictor of tumor relapse, but their role as a
      surrogate marker for TCs is limited. 

PMID- 25870254
TI  - Vitellibacter echinoideorum sp. nov., isolated from a sea urchin (Tripneustes
      gratilla).
AB  - A Gram-stain-negative, aerobic, rod-shaped, yellow-pigment-producing bacterium
      (designated strain CC-CZW007(T)) was isolated from seafood samples (sea urchins)
      at Penghu Island in Taiwan. Strain CC-CZW007(T) grew optimally at pH 7.0 and 30 
      degrees C in the presence of 3% (w/v) NaCl. The novel strain shared highest 16S
      rRNA gene sequence similarity to Vitellibacter vladivostokensis JCM 11732(T)
      (96.8%), Vitellibacter soesokkakensis KCTC 32536(T) (96.4%), Vitellibacter
      nionensis KCTC 32420(T) (95.8%) and Vitellibacter aestuarii JCM 15496(T) (95.6%)
      and lower sequence similarity to members of other genera. Phylogenetic analyses
      based on 16S rRNA genes revealed a distinct taxonomic position attained by strain
      CC-CZW007(T) with respect to other species of the genus Vitellibacter. The major
      fatty acids were iso-C15 : 0 and iso-C17 : 0 3-OH. The polar lipid profile was
      composed of major amounts of phosphatidylethanolamine, unidentified lipids and
      aminolipids; a moderate amount of aminophospholipid was also detected. The DNA G
      + C content was 34.7 mol%. The predominant quinone system was menaquinone (MK-6).
      On the basis of polyphasic taxonomic evidence presented here, strain CC-CZW007(T)
      is proposed to represent a novel species within the genus Vitellibacter, for
      which the name Vitellibacter echinoideorum sp. nov. is proposed. The type strain
      is CC-CZW007(T) ( = BCRC 80886(T) = JCM 30378(T)).

PMID- 25870255
TI  - Halorubrum gandharaense sp. nov., an alkaliphilic haloarchaeon from commercial
      rock salt.
AB  - A Gram-stain-negative, non-motile, pleomorphic rod-shaped, orange-red-pigmented,
      facultatively aerobic and haloalkaliphilic archaeon, strain MK13-1T, was isolated
      from commercial rock salt imported from Pakistan. The NaCl, pH and temperature
      ranges for growth of strain MK13-1T were 3.0-5.2 M NaCl, pH 8.0-11.0 and 15-50 
      degrees C, respectively. Optimal growth occurred at 3.2-3.4 M NaCl, pH 9.0-9.5
      and 45  degrees C. Addition of Mg2+ was not required for growth. The major polar
      lipids of the isolate were C20C20 and C20C25 archaeol derivatives of
      phosphatidylglycerol and phosphatidylglycerol phosphate methyl ester. Glycolipids
      were not detected. The DNA G+C content was 64.1 mol%. The 16S rRNA gene sequence
      of strain MK13-1T was most closely related to those of the species of the genus
      Halorubrum, Halorubrum luteum CECT 7303T (95.9% similarity), Halorubrum
      alkaliphilum JCM 12358T (95.3%), Halorubrum kocurii JCM 14978T (95.3%) and
      Halorubrum lipolyticum JCM 13559T (95.3%). The rpoB' gene sequence of strain MK13
      1T had < 90% sequence similarity to those of other members of the genus
      Halorubrum. Based on the phylogenetic analysis and phenotypic characterization,
      strain MK13-1T may represent a novel species of the genus Halorubrum, for which
      the name Halorubrum gandharaense sp. nov. is proposed, with the type strain MK13
      1T ( = JCM 17823T = CECT 7963T).

PMID- 25870256
TI  - Kangiella profundi sp. nov., isolated from deep-sea sediment.
AB  - A taxonomic study employing a polyphasic approach was carried out on strain
      FT102(T), which was isolated from a deep-sea sediment sample collected in the
      south-west Indian Ocean at a depth of 2784 m. The strain was Gram-stain-negative,
      non-motile, rod-shaped and non-spore-forming. It grew optimally at 37-42  degrees
      C, pH 6.5-8.5 and in the presence of 1-4% (w/v) NaCl. Phylogenetic analysis of
      16S rRNA gene sequences confirmed the separation of the novel strain from
      recognized members of the genus Kangiella that are available in public databases.
      Strain FT102(T) exhibited 95.5-98.6% 16S rRNA gene sequence similarity to the
      type strains of the eight recognized species of the genus Kangiella. The
      chemotaxonomically characteristic fatty acid iso-C15:0 and ubiquinone Q-8 were
      also detected. The major polar lipids were phosphatidylglycerol,
      diphosphatidylglycerol, phosphatidylethanolamine and
      phosphatidylmonomethylethanolamine. The DNA G + C content of strain FT102(T) was
      45.0 mol%. The mean DNA-DNA relatedness values between strain FT102(T) and the
      type strains of Kangiella aquimarina and Kangiella koreensis were 47.3% and
      13.7%, respectively. The combined results of phylogenetic, physiological and
      chemotaxonomic studies indicated that strain FT102(T) was affiliated with the
      genus Kangiella but differed from the recognized species of the genus Kangiella.
      Therefore, strain FT102T represents a novel species of the genus Kangiella, for
      which the name Kangiella profundi sp. nov. is proposed. The type strain is
      FT102(T) ( = CGMCC 1.12959(T) = KCTC 42297(T) = JCM 30232(T)).

PMID- 25870258
TI  - Mycobacterium anyangense sp. nov., a rapidly growing species isolated from blood
      of Korean native cattle, Hanwoo (Bos taurus coreanae).
AB  - From the whole blood of Korean native cattle, Hanwoo (Bos taurus coreanae), a
      previously undescribed, rapidly growing, scotochromogenic isolate of the genus
      Mycobacterium is reported. Its 16S rRNA gene sequence, and the sequences of three
      other genes (hsp65, recA and rpoB) were unique and phylogenetic analysis based on
      16S rRNA gene sequence (1420 bp) placed the organism into the rapidly growing
      Mycobacterium group close to Mycobacterium smegmatis (98.5% sequence similarity).
      However, phylogenetic analyses based on three different gene sequences (hsp65,
      recA and rpoB) revealed its location to be distinct from the branch of rapidly
      growing species. Culture and biochemical characteristics were generally similar
      to those of Mycobacterium fortuitum. Unique matrix-assisted laser desorption
      ionization time-of-flight (MALDI-TOF) MS profiles of lipids, unique fatty acid
      profile, unique mycolic acids profiles and a low DNA-DNA relatedness to M.
      fortuitum (23.6%) and M. smegmatis (39.7%) strongly supported the taxonomic
      status of this strain as a representative of a novel species of rapidly growing
      mycobacteria named Mycobacterium anyangense. The type strain is strain QIA-38(T)
      ( = JCM 30275(T) = KCTC 29443(T)).

PMID- 25870259
TI  - Membrane fusion during phage lysis.
AB  - In general, phages cause lysis of the bacterial host to effect release of the
      progeny virions. Until recently, it was thought that degradation of the
      peptidoglycan (PG) was necessary and sufficient for osmotic bursting of the cell.
      Recently, we have shown that in Gram-negative hosts, phage lysis also requires
      the disruption of the outer membrane (OM). This is accomplished by spanins, which
      are phage-encoded proteins that connect the cytoplasmic membrane (inner membrane,
      IM) and the OM. The mechanism by which the spanins destroy the OM is unknown.
      Here we show that the spanins of the paradigm coliphage lambda mediate efficient
      membrane fusion. This supports the notion that the last step of lysis is the
      fusion of the IM and OM. Moreover, data are provided indicating that spanin
      mediated fusion is regulated by the meshwork of the PG, thus coupling fusion to
      murein degradation by the phage endolysin. Because endolysin function requires
      the formation of MUm-scale holes by the phage holin, the lysis pathway is seen to
      require dramatic dynamics on the part of the OM and IM, as well as destruction of
      the PG. 

PMID- 25870260
TI  - Mechanically-driven phase separation in a growing bacterial colony.
AB  - Secretion of extracellular polymeric substances (EPSs) by growing bacteria is an
      integral part of forming biofilm-like structures. In such dense systems,
      mechanical interactions among the structural components can be expected to
      significantly contribute to morphological properties. Here, we use a particle
      based modeling approach to study the self-organization of nonmotile rod-shaped
      bacterial cells growing on a solid substrate in the presence of self-produced
      EPSs. In our simulation, all of the components interact mechanically via
      repulsive forces, occurring as the bacterial cells grow and divide (via consuming
      diffusing nutrient) and produce EPSs. Based on our simulation, we show that
      mechanical interactions control the collective behavior of the system. In
      particular, we find that the presence of nonadsorbing EPSs can lead to
      spontaneous aggregation of bacterial cells by a depletion attraction and thereby
      generates phase separated patterns in the nonequilibrium growing colony. Both
      repulsive interactions between cell and EPSs and the overall concentration of
      EPSs are important factors in the self-organization in a nonequilibrium growing
      colony. Furthermore, we investigate the interplay of mechanics with the nutrient
      diffusion and consumption by bacterial cells and observe that suppression of
      branch formation occurs due to EPSs compared with the case where no EPS is
      produced. 

PMID- 25870261
TI  - Electrochemical detection of a single cytomegalovirus at an ultramicroelectrode
      and its antibody anchoring.
AB  - We report observations of stochastic collisions of murine cytomegalovirus (MCMV)
      on ultramicroelectrodes (UMEs), extending the observation of discrete collision
      events on UMEs to biologically relevant analytes. Adsorption of an antibody
      specific for a virion surface glycoprotein allowed differentiation of MCMV from
      MCMV bound by antibody from the collision frequency decrease and current
      magnitudes in the electrochemical collision experiments, which shows the efficacy
      of the method to size viral samples. To add selectivity to the technique,
      interactions between MCMV, a glycoprotein-specific primary antibody to MCMV, and
      polystyrene bead "anchors," which were functionalized with a secondary antibody
      specific to the Fc region of the primary antibody, were used to affect virus
      mobility. Bead aggregation was observed, and the extent of aggregation was
      measured using the electrochemical collision technique. Scanning electron
      microscopy and optical microscopy further supported aggregate shape and extent of
      aggregation with and without MCMV. This work extends the field of collisions to
      biologically relevant antigens and provides a novel foundation upon which
      qualitative sensor technology might be built for selective detection of viruses
      and other biologically relevant analytes. 

PMID- 25870262
TI  - Assaying the kinetics of protein denaturation catalyzed by AAA+ unfolding
      machines and proteases.
AB  - ATP-dependent molecular machines of the AAA+ superfamily unfold or remodel
      proteins in all cells. For example, AAA+ ClpX and ClpA hexamers collaborate with
      the self-compartmentalized ClpP peptidase to unfold and degrade specific proteins
      in bacteria and some eukaryotic organelles. Although degradation assays are
      straightforward, robust methods to assay the kinetics of enzyme-catalyzed protein
      unfolding in the absence of proteolysis have been lacking. Here, we describe a
      FRET-based assay in which enzymatic unfolding converts a mixture of donor-labeled
      and acceptor-labeled homodimers into heterodimers. In this assay, ClpX is a more
      efficient protein-unfolding machine than ClpA both kinetically and in terms of
      ATP consumed. However, ClpP enhances the mechanical activities of ClpA
      substantially, and ClpAP degrades the dimeric substrate faster than ClpXP. When
      ClpXP or ClpAP engage the dimeric subunit, one subunit is actively unfolded and
      degraded, whereas the other subunit is passively unfolded by loss of its partner
      and released. This assay should be broadly applicable for studying the mechanisms
      of AAA+ proteases and remodeling chaperones. 

PMID- 25870263
TI  - Metabolic reprogramming in triple-negative breast cancer through Myc suppression
      of TXNIP.
AB  - Triple-negative breast cancers (TNBCs) are aggressive and lack targeted
      therapies. Understanding how nutrients are used in TNBCs may provide new targets
      for therapeutic intervention. We demonstrate that the transcription factor c-Myc
      drives glucose metabolism in TNBC cells but does so by a previously unappreciated
      mechanism that involves direct repression of thioredoxin-interacting protein
      (TXNIP). TXNIP is a potent negative regulator of glucose uptake, aerobic
      glycolysis, and glycolytic gene expression; thus its repression by c-Myc provides
      an alternate route to c-Myc-driven glucose metabolism. c-Myc reduces TXNIP gene
      expression by binding to an E-box-containing region in the TXNIP promoter,
      possibly competing with the related transcription factor MondoA. TXNIP
      suppression increases glucose uptake and drives a dependence on glycolysis.
      Ectopic TXNIP expression decreases glucose uptake, reduces cell proliferation,
      and increases apoptosis. Supporting the biological significance of the reciprocal
      relationship between c-Myc and TXNIP, a Mychigh/TXNIPlow gene signature
      correlates with decreased overall survival and decreased metastasis-free survival
      in breast cancer. The correlation between the Mychigh/TXNIPlow gene signature and
      poor clinical outcome is evident only in TNBC, not in other breast cancer
      subclasses. Mutation of TP53, which is a defining molecular feature of TNBC,
      enhances the correlation between the Mychigh/TXNIPlow gene signature and death
      from breast cancer. Because Myc drives nutrient utilization and TXNIP restricts
      glucose availability, we propose that the Mychigh/TXNIPlow gene signature
      coordinates nutrient utilization with nutrient availability. Further, our data
      suggest that loss of the p53 tumor suppressor cooperates with Mychigh/TXNIPlow
      driven metabolic dysregulation to drive the aggressive clinical behavior of TNBC.

PMID- 25870264
TI  - Multifunctional bioscaffolds for 3D culture of melanoma cells reveal increased
      MMP activity and migration with BRAF kinase inhibition.
AB  - Matrix metalloproteinases (MMPs) are important for many different types of cancer
      related processes, including metastasis. Understanding the functional impact of
      changes in MMP activity during cancer treatment is an important facet not
      typically evaluated as part of preclinical research. With MMP activity being a
      critical component of the metastatic cascade, we designed a 3D hydrogel system to
      probe whether pharmacological inhibition affected human melanoma cell proteolytic
      activity; metastatic melanoma is a highly aggressive and drug-resistant form of
      skin cancer. The relationship between MMP activity and drug treatment is unknown,
      and therefore we used an in situ fluorogenic MMP sensor peptide to determine how
      drug treatment affects melanoma cell MMP activity in three dimensions. We
      encapsulated melanoma cells from varying stages of progression within PEG-based
      hydrogels to examine the relationship between drug treatment and MMP activity.
      From these results, a metastatic melanoma cell line (A375) and two inhibitors
      that inhibit RAF (PLX4032 and sorafenib) were studied further to determine
      whether changes in MMP activity led to a functional change in cell behavior. A375
      cells exhibited increased MMP activity despite an overall decrease in metabolic
      activity with PLX4032 treatment. The changes in proteolytic activity correlated
      with increased cell elongation and increased single-cell migration. In contrast,
      sorafenib did not alter MMP activity or cell motility, showing that the changes
      induced by PLX4032 were not a universal response to small-molecule inhibition.
      Therefore, we argue the importance of studying MMP activity with drug treatment
      and its possible implications for unwanted side effects. 

PMID- 25870265
TI  - Volcanic history of the Imbrium basin: A close-up view from the lunar rover Yutu.
AB  - We report the surface exploration by the lunar rover Yutu that landed on the
      young lava flow in the northeastern part of the Mare Imbrium, which is the
      largest basin on the nearside of the Moon and is filled with several basalt units
      estimated to date from 3.5 to 2.0 Ga. The onboard lunar penetrating radar
      conducted a 114-m-long profile, which measured a thickness of ~5 m of the lunar
      regolith layer and detected three underlying basalt units at depths of 195, 215,
      and 345 m. The radar measurements suggest underestimation of the global lunar
      regolith thickness by other methods and reveal a vast volume of the last volcano
      eruption. The in situ spectral reflectance and elemental analysis of the lunar
      soil at the landing site suggest that the young basalt could be derived from an
      ilmenite-rich mantle reservoir and then assimilated by 10-20% of the last
      residual melt of the lunar magma ocean. 

PMID- 25870266
TI  - Post-treatment control of HIV infection.
AB  - Antiretroviral therapy (ART) for HIV is not a cure. However, recent studies
      suggest that ART, initiated early during primary infection, may induce post
      treatment control (PTC) of HIV infection with HIV RNA maintained at <50 copies
      per mL. We investigate the hypothesis that ART initiated early during primary
      infection permits PTC by limiting the size of the latent reservoir, which, if
      small enough at treatment termination, may allow the adaptive immune response to
      prevent viral rebound (VR) and control infection. We use a mathematical model of
      within host HIV dynamics to capture interactions among target cells, productively
      infected cells, latently infected cells, virus, and cytotoxic T lymphocytes
      (CTLs). Analysis of our model reveals a range in CTL response strengths where a
      patient may show either VR or PTC, depending on the size of the latent reservoir
      at treatment termination. Below this range, patients will always rebound, whereas
      above this range, patients are predicted to behave like elite controllers. Using
      data on latent reservoir sizes in patients treated during primary infection, we
      also predict population-level VR times for noncontrollers consistent with
      observations. 

PMID- 25870267
TI  - Cryo-EM structure of the tetracycline resistance protein TetM in complex with a
      translating ribosome at 3.9-A resolution.
AB  - Ribosome protection proteins (RPPs) confer resistance to tetracycline by binding
      to the ribosome and chasing the drug from its binding site. Current models for
      RPP action are derived from 7.2- to 16-A resolution structures of RPPs bound to
      vacant or nontranslating ribosomes. Here we present a cryo-electron microscopy
      reconstruction of the RPP TetM in complex with a translating ribosome at 3.9-A
      resolution. The structure reveals the contacts of TetM with the ribosome,
      including interaction between the conserved and functionally critical C-terminal
      extension of TetM with a unique splayed conformation of nucleotides A1492 and
      A1493 at the decoding center of the small subunit. The resolution enables us to
      unambiguously model the side chains of the amino acid residues comprising loop
      III in domain IV of TetM, revealing that the tyrosine residues Y506 and Y507 are
      not responsible for drug-release as suggested previously but rather for
      intrafactor contacts that appear to stabilize the conformation of loop III.
      Instead, Pro509 at the tip of loop III is located directly within the
      tetracycline binding site where it interacts with nucleotide C1054 of the 16S
      rRNA, such that RPP action uses Pro509, rather than Y506/Y507, to directly
      dislodge and release tetracycline from the ribosome. 

PMID- 25870269
TI  - Revealing the climate of snowball Earth from Delta17O systematics of hydrothermal
      rocks.
AB  - The oxygen isotopic composition of hydrothermally altered rocks partly originates
      from the interacting fluid. We use the triple oxygen isotope composition
      ((17)O/(16)O, (18)O/(16)O) of Proterozoic rocks to reconstruct the (18)O/(16)O
      ratio of ancient meteoric waters. Some of these waters have originated from
      snowball Earth glaciers and thus give insight into the climate and hydrology of
      these critical intervals in Earth history. For a Paleoproterozoic [~2.3-2.4
      gigayears ago (Ga)] snowball Earth, delta(18)O = -43 +/- 30/00 is estimated for
      pristine meteoric waters that precipitated at low paleo-latitudes (<=35 degrees
      N). Today, such low (18)O/(16)O values are only observed in central Antarctica,
      where long distillation trajectories in combination with low condensation
      temperatures promote extreme (18)O depletion. For a Neoproterozoic (~0.6-0.7 Ga)
      snowball Earth, higher meltwater delta(18)O estimates of -21 +/- 30/00 imply less
      extreme climate conditions at similar paleo-latitudes (<=35 degrees N). Both
      estimates are single snapshots of ancient water samples and may not represent
      peak snowball Earth conditions. We demonstrate how (17)O/(16)O measurements
      provide information beyond traditional (18)O/(16)O measurements, even though all
      fractionation processes are purely mass dependent. 

PMID- 25870268
TI  - Meteorite-catalyzed syntheses of nucleosides and of other prebiotic compounds
      from formamide under proton irradiation.
AB  - Liquid formamide has been irradiated by high-energy proton beams in the presence
      of powdered meteorites, and the products of the catalyzed resulting syntheses
      were analyzed by mass spectrometry. Relative to the controls (no radiation, or no
      formamide, or no catalyst), an extremely rich, variegate, and prebiotically
      relevant panel of compounds was observed. The meteorites tested were
      representative of the four major classes: iron, stony iron, chondrites, and
      achondrites. The products obtained were amino acids, carboxylic acids,
      nucleobases, sugars, and, most notably, four nucleosides: cytidine, uridine,
      adenosine, and thymidine. In accordance with theoretical studies, the detection
      of HCN oligomers suggests the occurrence of mechanisms based on the generation of
      radical cyanide species (CN.) for the synthesis of nucleobases. Given that many
      of the compounds obtained are key components of extant organisms, these
      observations contribute to outline plausible exogenous high-energy-based
      prebiotic scenarios and their possible boundary conditions, as discussed. 

PMID- 25870270
TI  - Maternal transmission, sex ratio distortion, and mitochondria.
AB  - In virtually all multicellular eukaryotes, mitochondria are transmitted
      exclusively through one parent, usually the mother. In this short review, we
      discuss some of the major consequences of uniparental transmission of
      mitochondria, including deleterious effects in males and selection for increased
      transmission through females. Many of these consequences, particularly sex ratio
      distortion, have well-studied parallels in other maternally transmitted genetic
      elements, such as bacterial endosymbionts of arthropods. We also discuss the
      consequences of linkage between mitochondria and other maternally transmitted
      genetic elements, including the role of cytonuclear incompatibilities in
      maintaining polymorphism. Finally, as a case study, we discuss a recently
      discovered maternally transmitted sex ratio distortion in an insect that is
      associated with extraordinarily divergent mitochondria. 

PMID- 25870271
TI  - Agricultural insecticides threaten surface waters at the global scale.
AB  - Compared with nutrient levels and habitat degradation, the importance of
      agricultural pesticides in surface water may have been underestimated due to a
      lack of comprehensive quantitative analysis. Increasing pesticide contamination
      results in decreasing regional aquatic biodiversity, i.e., macroinvertebrate
      family richness is reduced by ~30% at pesticide concentrations equaling the
      legally accepted regulatory threshold levels (RTLs). This study provides a
      comprehensive metaanalysis of 838 peer-reviewed studies (>2,500 sites in 73
      countries) that evaluates, for the first time to our knowledge on a global scale,
      the exposure of surface waters to particularly toxic agricultural insecticides.
      We tested whether measured insecticide concentrations (MICs; i.e., quantified
      insecticide concentrations) exceed their RTLs and how risks depend on insecticide
      development over time and stringency of environmental regulation. Our analysis
      reveals that MICs occur rarely (i.e., an estimated 97.4% of analyses conducted
      found no MICs) and there is a complete lack of scientific monitoring data for
      ~90% of global cropland. Most importantly, of the 11,300 MICs, 52.4% (5,915
      cases; 68.5% of the sites) exceeded the RTL for either surface water (RTLSW) or
      sediments. Thus, the biological integrity of global water resources is at a
      substantial risk. RTLSW exceedances depend on the catchment size, sampling
      regime, and sampling date; are significantly higher for newer-generation
      insecticides (i.e., pyrethroids); and are high even in countries with stringent
      environmental regulations. These results suggest the need for worldwide
      improvements to current pesticide regulations and agricultural pesticide
      application practices and for intensified research efforts on the presence and
      effects of pesticides under real-world conditions. 

PMID- 25870272
TI  - National hiring experiments reveal 2:1 faculty preference for women on STEM
      tenure track.
AB  - National randomized experiments and validation studies were conducted on 873
      tenure-track faculty (439 male, 434 female) from biology, engineering, economics,
      and psychology at 371 universities/colleges from 50 US states and the District of
      Columbia. In the main experiment, 363 faculty members evaluated narrative
      summaries describing hypothetical female and male applicants for tenure-track
      assistant professorships who shared the same lifestyle (e.g., single without
      children, married with children). Applicants' profiles were systematically varied
      to disguise identically rated scholarship; profiles were counterbalanced by
      gender across faculty to enable between-faculty comparisons of hiring preferences
      for identically qualified women versus men. Results revealed a 2:1 preference for
      women by faculty of both genders across both math-intensive and non-math
      intensive fields, with the single exception of male economists, who showed no
      gender preference. Results were replicated using weighted analyses to control for
      national sample characteristics. In follow-up experiments, 144 faculty evaluated
      competing applicants with differing lifestyles (e.g., divorced mother vs. married
      father), and 204 faculty compared same-gender candidates with children, but
      differing in whether they took 1-y-parental leaves in graduate school. Women
      preferred divorced mothers to married fathers; men preferred mothers who took
      leaves to mothers who did not. In two validation studies, 35 engineering faculty
      provided rankings using full curricula vitae instead of narratives, and 127
      faculty rated one applicant rather than choosing from a mixed-gender group; the
      same preference for women was shown by faculty of both genders. These results
      suggest it is a propitious time for women launching careers in academic science.
      Messages to the contrary may discourage women from applying for STEM (science,
      technology, engineering, mathematics) tenure-track assistant professorships. 

PMID- 25870273
TI  - Digital diffraction analysis enables low-cost molecular diagnostics on a
      smartphone.
AB  - The widespread distribution of smartphones, with their integrated sensors and
      communication capabilities, makes them an ideal platform for point-of-care (POC)
      diagnosis, especially in resource-limited settings. Molecular diagnostics,
      however, have been difficult to implement in smartphones. We herein report a
      diffraction-based approach that enables molecular and cellular diagnostics. The
      D3 (digital diffraction diagnosis) system uses microbeads to generate unique
      diffraction patterns which can be acquired by smartphones and processed by a
      remote server. We applied the D3 platform to screen for precancerous or cancerous
      cells in cervical specimens and to detect human papillomavirus (HPV) DNA. The D3
      assay generated readouts within 45 min and showed excellent agreement with gold
      standard pathology or HPV testing, respectively. This approach could have
      favorable global health applications where medical access is limited or when
      pathology bottlenecks challenge prompt diagnostic readouts. 

PMID- 25870274
TI  - Hypercholesterolemia and ApoE deficiency result in severe infection with Lyme
      disease and relapsing-fever Borrelia.
AB  - The Lyme disease (Borrelia burgdorferi) and relapsing-fever (Borrelia hispanica)
      agents have distinct infection courses, but both require cholesterol for growth.
      They acquire cholesterol from the environment and process it to form cholesterol
      glycolipids that are incorporated onto their membranes. To determine whether
      higher levels of serum cholesterol could enhance the organ burdens of B.
      burgdorferi and the spirochetemia of B. hispanica in laboratory mice,
      apolipoprotein E (apoE)-deficient and low-density lipoprotein receptor (LDLR)
      deficient mice that produce large amounts of serum cholesterol were infected with
      both spirochetes. Both apoE- and LDLR-deficient mice infected with B. burgdorferi
      had an increased number of spirochetes in the joints and inflamed ankles compared
      with the infected wild-type (WT) mice, suggesting that mutations in cholesterol
      transport that result in high serum cholesterol levels can affect the
      pathogenicity of B. burgdorferi. In contrast, elevated serum cholesterol did not
      lead to an increase in the spirochetemia of B. hispanica. In the LDLR-deficient
      mice, the course of infection was indistinguishable from the WT mice. However,
      infection of apoE-deficient mice with B. hispanica resulted in a longer
      spirochetemia and increased mortality. Together, these results argue for the apoE
      deficiency, and not hypercholesterolemia, as the cause for the increased severity
      with B. hispanica. Serum hyperlipidemias are common human diseases that could be
      a risk factor for increased severity in Lyme disease. 

PMID- 25870275
TI  - Plant immunity triggered by engineered in vivo release of oligogalacturonides,
      damage-associated molecular patterns.
AB  - Oligogalacturonides (OGs) are fragments of pectin that activate plant innate
      immunity by functioning as damage-associated molecular patterns (DAMPs). We set
      out to test the hypothesis that OGs are generated in planta by partial inhibition
      of pathogen-encoded polygalacturonases (PGs). A gene encoding a fungal PG was
      fused with a gene encoding a plant polygalacturonase-inhibiting protein (PGIP)
      and expressed in transgenic Arabidopsis plants. We show that expression of the
      PGIP-PG chimera results in the in vivo production of OGs that can be detected by
      mass spectrometric analysis. Transgenic plants expressing the chimera under
      control of a pathogen-inducible promoter are more resistant to the phytopathogens
      Botrytis cinerea, Pectobacterium carotovorum, and Pseudomonas syringae. These
      data provide strong evidence for the hypothesis that OGs released in vivo act as
      a DAMP signal to trigger plant immunity and suggest that controlled release of
      these molecules upon infection may be a valuable tool to protect plants against
      infectious diseases. On the other hand, elevated levels of expression of the
      chimera cause the accumulation of salicylic acid, reduced growth, and eventually
      lead to plant death, consistent with the current notion that trade-off occurs
      between growth and defense. 

PMID- 25870276
TI  - Inhibition of TLR2 signaling by small molecule inhibitors targeting a pocket
      within the TLR2 TIR domain.
AB  - Toll-like receptor (TLR) signaling is initiated by dimerization of intracellular
      Toll/IL-1 receptor resistance (TIR) domains. For all TLRs except TLR3,
      recruitment of the adapter, myeloid differentiation primary response gene 88
      (MyD88), to TLR TIR domains results in downstream signaling culminating in
      proinflammatory cytokine production. Therefore, blocking TLR TIR dimerization may
      ameliorate TLR2-mediated hyperinflammatory states. The BB loop within the TLR TIR
      domain is critical for mediating certain protein-protein interactions.
      Examination of the human TLR2 TIR domain crystal structure revealed a pocket
      adjacent to the highly conserved P681 and G682 BB loop residues. Using computer
      aided drug design (CADD), we sought to identify a small molecule inhibitor(s)
      that would fit within this pocket and potentially disrupt TLR2 signaling. In
      silico screening identified 149 compounds and 20 US Food and Drug Administration
      approved drugs based on their predicted ability to bind in the BB loop pocket.
      These compounds were screened in HEK293T-TLR2 transfectants for the ability to
      inhibit TLR2-mediated IL-8 mRNA. C16H15NO4 (C29) was identified as a potential
      TLR2 inhibitor. C29, and its derivative, ortho-vanillin (o-vanillin), inhibited
      TLR2/1 and TLR2/6 signaling induced by synthetic and bacterial TLR2 agonists in
      human HEK-TLR2 and THP-1 cells, but only TLR2/1 signaling in murine macrophages.
      C29 failed to inhibit signaling induced by other TLR agonists and TNF-alpha.
      Mutagenesis of BB loop pocket residues revealed an indispensable role for TLR2/1,
      but not TLR2/6, signaling, suggesting divergent roles. Mice treated with o
      vanillin exhibited reduced TLR2-induced inflammation. Our data provide proof of
      principle that targeting the BB loop pocket is an effective approach for
      identification of TLR2 signaling inhibitors. 

PMID- 25870277
TI  - Stat1 stimulates cap-independent mRNA translation to inhibit cell proliferation
      and promote survival in response to antitumor drugs.
AB  - The signal transducer and activator of transcription 1 (Stat1) functions as a
      tumor suppressor via immune regulatory and cell-autonomous pathways. Herein, we
      report a previously unidentified cell-autonomous Stat1 function, which is its
      ability to exhibit both antiproliferative and prosurvival properties by
      facilitating translation of mRNAs encoding for the cyclin-dependent kinase
      inhibitor p27(Kip1) and antiapoptotic proteins X-linked inhibitor of apoptosis
      and B-cell lymphoma xl. Translation of the select mRNAs requires the
      transcriptional function of Stat1, resulting in the up-regulation of the
      p110gamma subunit of phosphoinositide 3-kinase (PI3K) class IB and increased
      expression of the translational repressor translation initiation factor 4E
      (eIF4E)-binding protein 1 (4EBP1). Increased PI3Kgamma signaling promotes the
      degradation of the eIF4A inhibitor programmed cell death protein 4, which favors
      the cap-independent translation of the select mRNAs under conditions of general
      inhibition of protein synthesis by up-regulated eIF4E-binding protein 1. As such,
      Stat1 inhibits cell proliferation but also renders cells increasingly resistant
      to antiproliferative effects of pharmacological inhibitors of PI3K and/or
      mammalian target of rapamycin. Stat1 also protects Ras-transformed cells from the
      genotoxic effects of doxorubicin in culture and immune-deficient mice. Our
      findings demonstrate an important role of mRNA translation in the cell-autonomous
      Stat1 functions, with implications in tumor growth and treatment with
      chemotherapeutic drugs. 

PMID- 25870278
TI  - Hyperammonemia in gene-targeted mice lacking functional hepatic glutamine
      synthetase.
AB  - Urea cycle defects and acute or chronic liver failure are linked to systemic
      hyperammonemia and often result in cerebral dysfunction and encephalopathy.
      Although an important role of the liver in ammonia metabolism is widely accepted,
      the role of ammonia metabolizing pathways in the liver for maintenance of whole
      body ammonia homeostasis in vivo remains ill-defined. Here, we show by generation
      of liver-specific Gln synthetase (GS)-deficient mice that GS in the liver is
      critically involved in systemic ammonia homeostasis in vivo. Hepatic deletion of
      GS triggered systemic hyperammonemia, which was associated with cerebral
      oxidative stress as indicated by increased levels of oxidized RNA and enhanced
      protein Tyr nitration. Liver-specific GS-deficient mice showed increased
      locomotion, impaired fear memory, and a slightly reduced life span. In
      conclusion, the present observations highlight the importance of hepatic GS for
      maintenance of ammonia homeostasis and establish the liver-specific GS KO mouse
      as a model with which to study effects of chronic hyperammonemia. 

PMID- 25870280
TI  - High-throughput patterning of photonic structures with tunable periodicity.
AB  - A patterning method termed "RIPPLE" (reactive interface patterning promoted by
      lithographic electrochemistry) is applied to the fabrication of arrays of
      dielectric and metallic optical elements. This method uses cyclic voltammetry to
      impart patterns onto the working electrode of a standard three-electrode
      electrochemical setup. Using this technique and a template stripping process,
      periodic arrays of Ag circular Bragg gratings are patterned in a high-throughput
      fashion over large substrate areas. By varying the scan rate of the cyclically
      applied voltage ramps, the periodicity of the gratings can be tuned in situ over
      micrometer and submicrometer length scales. Characterization of the periodic
      arrays of periodic gratings identified point-like and annular scattering modes at
      different planes above the structured surface. Facile, reliable, and rapid
      patterning techniques like RIPPLE may enable the high-throughput and low-cost
      fabrication of photonic elements and metasurfaces for energy conversion and
      sensing applications. 

PMID- 25870279
TI  - Increased size and cellularity of advanced atherosclerotic lesions in mice with
      endothelial overexpression of the human TRPC3 channel.
AB  - In previous in vitro studies, we showed that Transient Receptor Potential
      Canonical 3 (TRPC3), a calcium-permeable, nonselective cation channel endowed
      with high constitutive function, is an obligatory component of the inflammatory
      signaling that controls expression of the vascular cell adhesion molecule-1 (VCAM
      1) and monocyte adhesion to coronary artery endothelial cells. Also, TRPC3
      expression in these cells was found to be up-regulated by proatherogenic factors,
      which enhanced inflammation and VCAM-1 expression. However, it remained to be
      determined whether these in vitro findings were of relevance to atherosclerotic
      lesion development in vivo. To answer this important question in the present
      work, we generated mice with endothelial-specific overexpression of human TRPC3
      in an Apoe knockout background (TgEST3ApoeKO) and examined lesions in the aortic
      sinus following 10 and 16 wk on a high-fat diet. No significant differences were
      found in size or complexity of early stage lesions (10 wk). However, advanced
      plaques (16 wk) from TgEST3ApoeKO mice exhibited a significant increase in size
      and macrophage content compared with nontransgenic littermate controls.
      Remarkably, this change was correlated with increased VCAM-1 and phospho-IkBalpha
      immunoreactivity along the endothelial lining of lesions from transgenic animals
      compared with controls. These findings validate the in vivo relevance of previous
      in vitro findings and represent, to our knowledge, the first in vivo evidence for
      a proatherogenic role of endothelial TRPC3. 

PMID- 25870281
TI  - Probing the energetics of organic-nanoparticle interactions of ethanol on
      calcite.
AB  - Knowing the nature of interactions between small organic molecules and surfaces
      of nanoparticles (NP) is crucial for fundamental understanding of natural
      phenomena and engineering processes. Herein, we report direct adsorption enthalpy
      measurement of ethanol on a series of calcite nanocrystals, with the aim of
      mimicking organic-NP interactions in various environments. The energetics
      suggests a spectrum of adsorption events as a function of coverage: strongest
      initial chemisorption on active sites on fresh calcite surfaces, followed by
      major chemical binding to form an ethanol monolayer and, subsequently, very weak,
      near-zero energy, physisorption. These thermochemical observations directly
      support a structure where the ethanol monolayer is bonded to the calcite surface
      through its polar hydroxyl group, leaving the hydrophobic ends of the ethanol
      molecules to interact only weakly with the next layer of adsorbing ethanol and
      resulting in a spatial gap with low ethanol density between the monolayer and
      subsequent added ethanol molecules, as predicted by molecular dynamics and
      density functional calculations. Such an ordered assembly of ethanol on calcite
      NP is analogous to, although less strongly bonded than, a capping layer of
      organics intentionally introduced during NP synthesis, and suggests a continuous
      variation of surface structure depending on molecular chemistry, ranging from
      largely disordered surface layers to ordered layers that nevertheless are mobile
      and can rearrange or be displaced by other molecules to strongly bonded immobile
      organic capping layers. These differences in surface structure will affect
      chemical reactions, including the further nucleation and growth of nanocrystals
      on organic ligand-capped surfaces. 

PMID- 25870283
TI  - Community clusters of tsunami vulnerability in the US Pacific Northwest.
AB  - Many coastal communities throughout the world are threatened by local (or near
      field) tsunamis that could inundate low-lying areas in a matter of minutes after
      generation. Although the hazard and sustainability literature often frames
      vulnerability conceptually as a multidimensional issue involving exposure,
      sensitivity, and resilience to a hazard, assessments often focus on one element
      or do not recognize the hazard context. We introduce an analytical framework for
      describing variations in population vulnerability to tsunami hazards that
      integrates (i) geospatial approaches to identify the number and characteristics
      of people in hazard zones, (ii) anisotropic path distance models to estimate
      evacuation travel times to safety, and (iii) cluster analysis to classify
      communities with similar vulnerability. We demonstrate this approach by
      classifying 49 incorporated cities, 7 tribal reservations, and 17 counties from
      northern California to northern Washington that are directly threatened by
      tsunami waves associated with a Cascadia subduction zone earthquake. Results
      suggest three primary community groups: (i) relatively low numbers of exposed
      populations with varied demographic sensitivities, (ii) high numbers of exposed
      populations but sufficient time to evacuate before wave arrival, and (iii)
      moderate numbers of exposed populations but insufficient time to evacuate.
      Results can be used to enhance general hazard-awareness efforts with targeted
      interventions, such as education and outreach tailored to local demographics,
      evacuation training, and/or vertical evacuation refuges. 

PMID- 25870282
TI  - MeCP2 binds to non-CG methylated DNA as neurons mature, influencing transcription
      and the timing of onset for Rett syndrome.
AB  - Epigenetic mechanisms, such as DNA methylation, regulate transcriptional programs
      to afford the genome flexibility in responding to developmental and environmental
      cues in health and disease. A prime example involving epigenetic dysfunction is
      the postnatal neurodevelopmental disorder Rett syndrome (RTT), which is caused by
      mutations in the gene encoding methyl-CpG binding protein 2 (MeCP2). Despite
      decades of research, it remains unclear how MeCP2 regulates transcription or why
      RTT features appear 6-18 months after birth. Here we report integrated analyses
      of genomic binding of MeCP2, gene-expression data, and patterns of DNA
      methylation. In addition to the expected high-affinity binding to methylated
      cytosine in the CG context (mCG), we find a distinct epigenetic pattern of
      substantial MeCP2 binding to methylated cytosine in the non-CG context (mCH,
      where H = A, C, or T) in the adult brain. Unexpectedly, we discovered that genes
      that acquire elevated mCH after birth become preferentially misregulated in mouse
      models of MeCP2 disorders, suggesting that MeCP2 binding at mCH loci is key for
      regulating neuronal gene expression in vivo. This pattern is unique to the
      maturing and adult nervous system, as it requires the increase in mCH after birth
      to guide differential MeCP2 binding among mCG, mCH, and nonmethylated DNA
      elements. Notably, MeCP2 binds mCH with higher affinity than nonmethylated
      identical DNA sequences to influence the level of Bdnf, a gene implicated in the
      pathophysiology of RTT. This study thus provides insight into the molecular
      mechanism governing MeCP2 targeting and sheds light on the delayed onset of RTT
      symptoms. 

PMID- 25870284
TI  - Glycolytic flux controls D-serine synthesis through glyceraldehyde-3-phosphate
      dehydrogenase in astrocytes.
AB  - D-Serine is an essential coagonist with glutamate for stimulation of N-methyl-D
      aspartate (NMDA) glutamate receptors. Although astrocytic metabolic processes are
      known to regulate synaptic glutamate levels, mechanisms that control D-serine
      levels are not well defined. Here we show that d-serine production in astrocytes
      is modulated by the interaction between the D-serine synthetic enzyme serine
      racemase (SRR) and a glycolytic enzyme, glyceraldehyde 3-phosphate dehydrogenase
      (GAPDH). In primary cultured astrocytes, glycolysis activity was negatively
      correlated with D-serine level. We show that SRR interacts directly with GAPDH,
      and that activation of glycolysis augments this interaction. Biochemical assays
      using mutant forms of GAPDH with either reduced activity or reduced affinity to
      SRR revealed that GAPDH suppresses SRR activity by direct binding to GAPDH and
      through NADH, a product of GAPDH. NADH allosterically inhibits the activity of
      SRR by promoting the disassociation of ATP from SRR. Thus, astrocytic production
      of D-serine is modulated by glycolytic activity via interactions between GAPDH
      and SRR. We found that SRR is expressed in astrocytes in the subiculum of the
      human hippocampus, where neurons are known to be particularly vulnerable to loss
      of energy. Collectively, our findings suggest that astrocytic energy metabolism
      controls D-serine production, thereby influencing glutamatergic neurotransmission
      in the hippocampus.

PMID- 25870285
TI  - Mitofusin 2 ablation increases endoplasmic reticulum-mitochondria coupling.
AB  - The organization and mutual interactions between endoplasmic reticulum (ER) and
      mitochondria modulate key aspects of cell pathophysiology. Several proteins have
      been suggested to be involved in keeping ER and mitochondria at a correct
      distance. Among them, in mammalian cells, mitofusin 2 (Mfn2), located on both the
      outer mitochondrial membrane and the ER surface, has been proposed to be a
      physical tether between the two organelles, forming homotypic interactions and
      heterocomplexes with its homolog Mfn1. Recently, this widely accepted model has
      been challenged using quantitative EM analysis. Using a multiplicity of
      morphological, biochemical, functional, and genetic approaches, we demonstrate
      that Mfn2 ablation increases the structural and functional ER-mitochondria
      coupling. In particular, we show that in different cell types Mfn2 ablation or
      silencing increases the close contacts between the two organelles and strengthens
      the efficacy of inositol trisphosphate (IP3)-induced Ca(2+) transfer from the ER
      to mitochondria, sensitizing cells to a mitochondrial Ca(2+) overload-dependent
      death. We also show that the previously reported discrepancy between electron and
      fluorescence microscopy data on ER-mitochondria proximity in Mfn2-ablated cells
      is only apparent. By using a different type of morphological analysis of
      fluorescent images that takes into account (and corrects for) the gross
      modifications in mitochondrial shape resulting from Mfn2 ablation, we demonstrate
      that an increased proximity between the organelles is also observed by confocal
      microscopy when Mfn2 levels are reduced. Based on these results, we propose a new
      model for ER-mitochondria juxtaposition in which Mfn2 works as a tethering
      antagonist preventing an excessive, potentially toxic, proximity between the two
      organelles. 

PMID- 25870286
TI  - Microgrooves and fluid flows provide preferential passageways for sperm over
      pathogen Tritrichomonas foetus.
AB  - Successful mammalian reproduction requires that sperm migrate through a long and
      convoluted female reproductive tract before reaching oocytes. For many years,
      fertility studies have focused on biochemical and physiological requirements of
      sperm. Here we show that the biophysical environment of the female reproductive
      tract critically guides sperm migration, while at the same time preventing the
      invasion of sexually transmitted pathogens. Using a microfluidic model, we
      demonstrate that a gentle fluid flow and microgrooves, typically found in the
      female reproductive tract, synergistically facilitate bull sperm migration toward
      the site of fertilization. In contrast, a flagellated sexually transmitted bovine
      pathogen, Tritrichomonas foetus, is swept downstream under the same conditions.
      We attribute the differential ability of sperm and T. foetus to swim against flow
      to the distinct motility types of sperm and T. foetus; specifically, sperm swim
      using a posterior flagellum and are near-surface swimmers, whereas T. foetus
      swims primarily via three anterior flagella and demonstrates much lower
      attraction to surfaces. This work highlights the importance of biophysical cues
      within the female reproductive tract in the reproductive process and provides
      insight into coevolution of males and females to promote fertilization while
      suppressing infection. Furthermore, the results provide previously unidentified
      directions for the development of in vitro fertilization devices and
      contraceptives. 

PMID- 25870287
TI  - Ab initio study of hot electrons in GaAs.
AB  - Hot carrier dynamics critically impacts the performance of electronic,
      optoelectronic, photovoltaic, and plasmonic devices. Hot carriers lose energy
      over nanometer lengths and picosecond timescales and thus are challenging to
      study experimentally, whereas calculations of hot carrier dynamics are cumbersome
      and dominated by empirical approaches. In this work, we present ab initio
      calculations of hot electrons in gallium arsenide (GaAs) using density functional
      theory and many-body perturbation theory. Our computed electron-phonon relaxation
      times at the onset of the Gamma, L, and X valleys are in excellent agreement with
      ultrafast optical experiments and show that the ultrafast (tens of femtoseconds)
      hot electron decay times observed experimentally arise from electron-phonon
      scattering. This result is an important advance to resolve a controversy on hot
      electron cooling in GaAs. We further find that, contrary to common notions, all
      optical and acoustic modes contribute substantially to electron-phonon
      scattering, with a dominant contribution from transverse acoustic modes. This
      work provides definitive microscopic insight into hot electrons in GaAs and
      enables accurate ab initio computation of hot carriers in advanced materials. 

PMID- 25870288
TI  - Dynamics of change in multiethnic societies: An archaeological perspective from
      colonial North America.
AB  - This Perspective presents an overview of the archaeology of pluralistic colonies
      (approximately late 1500s-1800s) in North America. It complements the other
      special feature papers in this issue on ancient societies in Mesoamerica, the
      Near East, the Armenian Highlands, Peru, and China by presenting another body of
      literature for examining the dynamics of change in multiethnic societies from a
      different time and place. In synthesizing archaeological investigations of
      mercantile, plantation, and missionary colonies, this Perspective shows how this
      research is relevant to the study of pluralism in both historic and ancient
      societies in three ways. (i) It enhances our understanding of interethnic
      relationships that took place in complex societies with imposing political
      hierarchies and labor structures. (ii) It helps us to refine the methods used by
      archaeologists to define and analyze multiethnic communities that were spatially
      delimited by ethnic neighborhoods. Finally, (iii) it presents more than a half
      century of experimentation with various models (e.g., acculturation,
      creolization, ethnogenesis, and hybridity) that have been used to study the
      dynamics of culture change in multiethnic societies. 

PMID- 25870289
TI  - Endogenous circadian system and circadian misalignment impact glucose tolerance
      via separate mechanisms in humans.
AB  - Glucose tolerance is lower in the evening and at night than in the morning.
      However, the relative contribution of the circadian system vs. the behavioral
      cycle (including the sleep/wake and fasting/feeding cycles) is unclear.
      Furthermore, although shift work is a diabetes risk factor, the separate impact
      on glucose tolerance of the behavioral cycle, circadian phase, and circadian
      disruption (i.e., misalignment between the central circadian pacemaker and the
      behavioral cycle) has not been systematically studied. Here we show--by using two
      8-d laboratory protocols--in healthy adults that the circadian system and
      circadian misalignment have distinct influences on glucose tolerance, both
      separate from the behavioral cycle. First, postprandial glucose was 17% higher
      (i.e., lower glucose tolerance) in the biological evening (8:00 PM) than morning
      (8:00 AM; i.e., a circadian phase effect), independent of the behavioral cycle
      effect. Second, circadian misalignment itself (12-h behavioral cycle inversion)
      increased postprandial glucose by 6%. Third, these variations in glucose
      tolerance appeared to be explained, at least in part, by different mechanisms:
      during the biological evening by decreased pancreatic beta-cell function (27%
      lower early-phase insulin) and during circadian misalignment presumably by
      decreased insulin sensitivity (elevated postprandial glucose despite 14% higher
      late-phase insulin) without change in early-phase insulin. We explored possible
      contributing factors, including changes in polysomnographic sleep and 24-h
      hormonal profiles. We demonstrate that the circadian system importantly
      contributes to the reduced glucose tolerance observed in the evening compared
      with the morning. Separately, circadian misalignment reduces glucose tolerance,
      providing a mechanism to help explain the increased diabetes risk in shift
      workers.

PMID- 25870290
TI  - Activation of cyclic electron flow by hydrogen peroxide in vivo.
AB  - Cyclic electron flow (CEF) around photosystem I is thought to balance the
      ATP/NADPH energy budget of photosynthesis, requiring that its rate be finely
      regulated. The mechanisms of this regulation are not well understood. We observed
      that mutants that exhibited constitutively high rates of CEF also showed elevated
      production of H2O2. We thus tested the hypothesis that CEF can be activated by
      H2O2 in vivo. CEF was strongly increased by H2O2 both by infiltration or in situ
      production by chloroplast-localized glycolate oxidase, implying that H2O2 can
      activate CEF either directly by redox modulation of key enzymes, or indirectly by
      affecting other photosynthetic processes. CEF appeared with a half time of about
      20 min after exposure to H2O2, suggesting activation of previously expressed CEF
      related machinery. H2O2-dependent CEF was not sensitive to antimycin A or loss of
      PGR5, indicating that increased CEF probably does not involve the PGR5-PGRL1
      associated pathway. In contrast, the rise in CEF was not observed in a mutant
      deficient in the chloroplast NADPH:PQ reductase (NDH), supporting the involvement
      of this complex in CEF activated by H2O2. We propose that H2O2 is a missing link
      between environmental stress, metabolism, and redox regulation of CEF in higher
      plants. 

PMID- 25870291
TI  - Heightened potency of human pluripotent stem cell lines created by transient BMP4
      exposure.
AB  - Human pluripotent stem cells (PSCs) show epiblast-type pluripotency that is
      maintained with ACTIVIN/FGF2 signaling. Here, we report the acquisition of a
      unique stem cell phenotype by both human ES cells (hESCs) and induced pluripotent
      stem cells (iPSCs) in response to transient (24-36 h) exposure to bone
      morphogenetic protein 4 (BMP4) plus inhibitors of ACTIVIN signaling (A83-01) and
      FGF2 (PD173074), followed by trypsin dissociation and recovery of colonies
      capable of growing on a gelatin substratum in standard medium for human PSCs at
      low but not high FGF2 concentrations. The self-renewing cell lines stain weakly
      for CDX2 and strongly for NANOG, can be propagated clonally on either Matrigel or
      gelatin, and are morphologically distinct from human PSC progenitors on either
      substratum but still meet standard in vitro criteria for pluripotency. They form
      well-differentiated teratomas in immune-compromised mice that secrete human
      chorionic gonadotropin (hCG) into the host mouse and include small areas of
      trophoblast-like cells. The cells have a distinct transcriptome profile from the
      human PSCs from which they were derived (including higher expression of NANOG,
      LEFTY1, and LEFTY2). In nonconditioned medium lacking FGF2, the colonies
      spontaneously differentiated along multiple lineages, including trophoblast. They
      responded to PD173074 in the absence of both FGF2 and BMP4 by conversion to
      trophoblast, and especially syncytiotrophoblast, whereas an A83-01/PD173074
      combination favored increased expression of HLA-G, a marker of extravillous
      trophoblast. Together, these data suggest that the cell lines exhibit totipotent
      potential and that BMP4 can prime human PSCs to a self-renewing alternative state
      permissive for trophoblast development. The results may have implications for
      regulation of lineage decisions in the early embryo. 

PMID- 25870292
TI  - Protection in antibody- and T cell-mediated autoimmune diseases by
      antiinflammatory IgG Fcs requires type II FcRs.
AB  - The antiinflammatory activity of intravenous immunoglobulin (IVIG) is dependent
      on the presence of sialic acid in the core IgG fragment crystallizable domain
      (Fc) glycan, resulting in increased conformational flexibility of the CH2 domain
      with corresponding modulation of Fc receptor (FcR) binding specificity from type
      I to type II receptors. Sialylated IgG Fc (sFc) increases the activation
      threshold of innate effector cells to immune complexes by stimulating the up
      regulation of the inhibitory receptor FcgammaRIIB. We have found that the
      structural alterations induced by sialylation can be mimicked by specific amino
      acid modifications to the CH2 domain. An IgG Fc variant with a point mutation at
      position 241 (F->A) exhibits antiinflammatory activity even in the absence of
      sialylation. F241A and sFc protect mice from arthritis in the K/BxN-induced model
      and, in the T cell-mediated experimental autoimmune encephalomyelitis (EAE) mouse
      model, suppress disease by specifically activating regulatory T cells (Treg
      cells). Protection by these antiinflammatory Fcs in both antibody- and T cell
      mediated autoimmune diseases required type II FcRs and the induction of IL-33.
      These results further clarify the mechanism of action of IVIG in both antibody-
      and T cell-mediated inflammatory diseases and demonstrate that Fc variants that
      mimic the structural alterations induced by sialylation, such as F241A, can be
      promising therapeutic candidates for the treatment of various autoimmune
      disorders. 

PMID- 25870294
TI  - Understanding scaling through history-dependent processes with collapsing sample
      space.
AB  - History-dependent processes are ubiquitous in natural and social systems. Many
      such stochastic processes, especially those that are associated with complex
      systems, become more constrained as they unfold, meaning that their sample space,
      or their set of possible outcomes, reduces as they age. We demonstrate that these
      sample-space-reducing (SSR) processes necessarily lead to Zipf's law in the rank
      distributions of their outcomes. We show that by adding noise to SSR processes
      the corresponding rank distributions remain exact power laws, p(x) ~ x(-lambda),
      where the exponent directly corresponds to the mixing ratio of the SSR process
      and noise. This allows us to give a precise meaning to the scaling exponent in
      terms of the degree to which a given process reduces its sample space as it
      unfolds. Noisy SSR processes further allow us to explain a wide range of scaling
      exponents in frequency distributions ranging from alpha = 2 to infinity. We
      discuss several applications showing how SSR processes can be used to understand
      Zipf's law in word frequencies, and how they are related to diffusion processes
      in directed networks, or aging processes such as in fragmentation processes. SSR
      processes provide a new alternative to understand the origin of scaling in
      complex systems without the recourse to multiplicative, preferential, or self
      organized critical processes.

PMID- 25870293
TI  - Neuronal medium that supports basic synaptic functions and activity of human
      neurons in vitro.
AB  - Human cell reprogramming technologies offer access to live human neurons from
      patients and provide a new alternative for modeling neurological disorders in
      vitro. Neural electrical activity is the essence of nervous system function in
      vivo. Therefore, we examined neuronal activity in media widely used to culture
      neurons. We found that classic basal media, as well as serum, impair action
      potential generation and synaptic communication. To overcome this problem, we
      designed a new neuronal medium (BrainPhys basal + serum-free supplements) in
      which we adjusted the concentrations of inorganic salts, neuroactive amino acids,
      and energetic substrates. We then tested that this medium adequately supports
      neuronal activity and survival of human neurons in culture. Long-term exposure to
      this physiological medium also improved the proportion of neurons that were
      synaptically active. The medium was designed to culture human neurons but also
      proved adequate for rodent neurons. The improvement in BrainPhys basal medium to
      support neurophysiological activity is an important step toward reducing the gap
      between brain physiological conditions in vivo and neuronal models in vitro. 

PMID- 25870295
TI  - Host attachment and fluid shear are integrated into a mechanical signal
      regulating virulence in Escherichia coli O157:H7.
AB  - Enterohemorrhagic Escherichia coli (EHEC) is a foodborne pathogen causing
      hemorrhagic colitis and hemolytic uremic syndrome. EHEC colonizes the intestinal
      tract through a range of virulence factors encoded by the locus of enterocyte
      effacement (LEE), as well as Shiga toxin. Although the factors involved in
      colonization and disease are well characterized, how EHEC regulates its
      expression in response to a host encounter is not well understood. Here, we
      report that EHEC perceives attachment to host cells as a mechanical cue that
      leads to expression of LEE-encoded virulence genes. This signal is transduced via
      the LEE-encoded global regulator of LEE-encoded regulator (Ler) and global
      regulator of Ler and is further enhanced by levels of shear force similar to
      peristaltic forces in the intestinal tract. Our data suggest that, in addition to
      a range of chemical environmental signals, EHEC is capable of sensing and
      responding to mechanical cues to adapt to its host's physiology. 

PMID- 25870296
TI  - Enhancement of radiation effect on cancer cells by gold-pHLIP.
AB  - Previous research has shown that gold nanoparticles can increase the
      effectiveness of radiation on cancer cells. Improved radiation effectiveness
      would allow lower radiation doses given to patients, reducing adverse effects;
      alternatively, it would provide more cancer killing at current radiation doses.
      Damage from radiation and gold nanoparticles depends in part on the Auger effect,
      which is very localized; thus, it is important to place the gold nanoparticles on
      or in the cancer cells. In this work, we use the pH-sensitive, tumor-targeting
      agent, pH Low-Insertion Peptide (pHLIP), to tether 1.4-nm gold nanoparticles to
      cancer cells. We find that the conjugation of pHLIP to gold nanoparticles
      increases gold uptake in cells compared with gold nanoparticles without pHLIP,
      with the nanoparticles distributed mostly on the cellular membranes. We further
      find that gold nanoparticles conjugated to pHLIP produce a statistically
      significant decrease in cell survival with radiation compared with cells without
      gold nanoparticles and cells with gold alone. In the context of our previous
      findings demonstrating efficient pHLIP-mediated delivery of gold nanoparticles to
      tumors, the obtained results serve as a foundation for further preclinical
      evaluation of dose enhancement. 

PMID- 25870297
TI  - Induced transcription and stability of CELF2 mRNA drives widespread alternative
      splicing during T-cell signaling.
AB  - Studies in several cell types have highlighted dramatic and diverse changes in
      mRNA processing that occur upon cellular stimulation. However, the mechanisms and
      pathways that lead to regulated changes in mRNA processing remain poorly
      understood. Here we demonstrate that expression of the splicing factor CELF2
      (CUGBP, Elav-like family member 2) is regulated in response to T-cell signaling
      through combined increases in transcription and mRNA stability. Transcriptional
      induction occurs within 6 h of stimulation and is dependent on activation of NF
      kappaB. Subsequently, there is an increase in the stability of the CELF2 mRNA
      that correlates with a change in CELF2 3'UTR length and contributes to the total
      signal-induced enhancement of CELF2 expression. Importantly, we uncover dozens of
      splicing events in cultured T cells whose changes upon stimulation are dependent
      on CELF2 expression, and provide evidence that CELF2 controls a similar
      proportion of splicing events during human thymic T-cell development. Taken
      together, these findings expand the physiologic impact of CELF2 beyond that
      previously documented in developing neuronal and muscle cells to T-cell
      development and function, identify unappreciated instances of alternative
      splicing in the human thymus, and uncover novel mechanisms for CELF2 regulation
      that may broadly impact CELF2 expression across diverse cell types. 

PMID- 25870298
TI  - Meteorite zircon constraints on the bulk Lu-Hf isotope composition and early
      differentiation of the Earth.
AB  - Knowledge of planetary differentiation is crucial for understanding the chemical
      and thermal evolution of terrestrial planets. The (176)Lu-(176)Hf radioactive
      decay system has been widely used to constrain the timescales and mechanisms of
      silicate differentiation on Earth, but the data interpretation requires accurate
      estimation of Hf isotope evolution of the bulk Earth. Because both Lu and Hf are
      refractory lithophile elements, the isotope evolution can be potentially
      extrapolated from the present-day (176)Hf/(177)Hf and (176)Lu/(177)Hf in
      undifferentiated chondrite meteorites. However, these ratios in chondrites are
      highly variable due to the metamorphic redistribution of Lu and Hf, making it
      difficult to ascertain the correct reference values for the bulk Earth. In
      addition, it has been proposed that chondrites contain excess (176)Hf due to the
      accelerated decay of (176)Lu resulting from photoexcitation to a short-lived
      isomer. If so, the paradigm of a chondritic Earth would be invalid for the Lu-Hf
      system. Herein we report the first, to our knowledge, high-precision Lu-Hf
      isotope analysis of meteorite crystalline zircon, a mineral that is resistant to
      metamorphism and has low Lu/Hf. We use the meteorite zircon data to define the
      Solar System initial (176)Hf/(177)Hf (0.279781 +/- 0.000018) and further to
      identify pristine chondrites that contain no excess (176)Hf and accurately
      represent the Lu-Hf system of the bulk Earth ((176)Hf/(177)Hf = 0.282793 +/-
      0.000011; (176)Lu/(177)Hf = 0.0338 +/- 0.0001). Our results provide firm evidence
      that the most primitive Hf in terrestrial zircon reflects the development of a
      chemically enriched silicate reservoir on Earth as far back as 4.5 billion years
      ago. 

PMID- 25870299
TI  - Metatranscriptome analyses indicate resource partitioning between diatoms in the
      field.
AB  - Diverse communities of marine phytoplankton carry out half of global primary
      production. The vast diversity of the phytoplankton has long perplexed ecologists
      because these organisms coexist in an isotropic environment while competing for
      the same basic resources (e.g., inorganic nutrients). Differential niche
      partitioning of resources is one hypothesis to explain this "paradox of the
      plankton," but it is difficult to quantify and track variation in phytoplankton
      metabolism in situ. Here, we use quantitative metatranscriptome analyses to
      examine pathways of nitrogen (N) and phosphorus (P) metabolism in diatoms that
      cooccur regularly in an estuary on the east coast of the United States
      (Narragansett Bay). Expression of known N and P metabolic pathways varied between
      diatoms, indicating apparent differences in resource utilization capacity that
      may prevent direct competition. Nutrient amendment incubations skewed N/P ratios,
      elucidating nutrient-responsive patterns of expression and facilitating a
      quantitative comparison between diatoms. The resource-responsive (RR) gene sets
      deviated in composition from the metabolic profile of the organism, being
      enriched in genes associated with N and P metabolism. Expression of the RR gene
      set varied over time and differed significantly between diatoms, resulting in
      opposite transcriptional responses to the same environment. Apparent differences
      in metabolic capacity and the expression of that capacity in the environment
      suggest that diatom-specific resource partitioning was occurring in Narragansett
      Bay. This high-resolution approach highlights the molecular underpinnings of
      diatom resource utilization and how cooccurring diatoms adjust their cellular
      physiology to partition their niche space. 

PMID- 25870300
TI  - Interfacial self-assembly of a bacterial hydrophobin.
AB  - The majority of bacteria in the natural environment live within the confines of a
      biofilm. The Gram-positive bacterium Bacillus subtilis forms biofilms that
      exhibit a characteristic wrinkled morphology and a highly hydrophobic surface. A
      critical component in generating these properties is the protein BslA, which
      forms a coat across the surface of the sessile community. We recently reported
      the structure of BslA, and noted the presence of a large surface-exposed
      hydrophobic patch. Such surface patches are also observed in the class of surface
      active proteins known as hydrophobins, and are thought to mediate their
      interfacial activity. However, although functionally related to the hydrophobins,
      BslA shares no sequence nor structural similarity, and here we show that the
      mechanism of action is also distinct. Specifically, our results suggest that the
      amino acids making up the large, surface-exposed hydrophobic cap in the crystal
      structure are shielded in aqueous solution by adopting a random coil
      conformation, enabling the protein to be soluble and monomeric. At an interface,
      these cap residues refold, inserting the hydrophobic side chains into the air or
      oil phase and forming a three-stranded beta-sheet. This form then self-assembles
      into a well-ordered 2D rectangular lattice that stabilizes the interface. By
      replacing a hydrophobic leucine in the center of the cap with a positively
      charged lysine, we changed the energetics of adsorption and disrupted the
      formation of the 2D lattice. This limited structural metamorphosis represents a
      previously unidentified environmentally responsive mechanism for interfacial
      stabilization by proteins. 

PMID- 25870301
TI  - Shape-sensitive crystallization in colloidal superball fluids.
AB  - Guiding the self-assembly of materials by controlling the shape of the individual
      particle constituents is a powerful approach to material design. We show that
      colloidal silica superballs crystallize into canted phases in the presence of
      depletants. Some of these phases are consistent with the so-called "Lambda1"
      lattice that was recently predicted as the densest packing of superdisks. As the
      size of the depletant is reduced, however, we observe a transition to a square
      phase. The differences in these entropically stabilized phases result from an
      interplay between the size of the depletants and the fine structure of the
      superball shape. We find qualitative agreement of our experimental results both
      with a phase diagram computed on the basis of the volume accessible to the
      depletants and with simulations. By using a mixture of depletants, one of which
      is thermosensitive, we induce solid-to-solid phase transitions between square and
      canted structures. The use of depletant size to leverage fine features of the
      shape of particles in driving their self-assembly demonstrates a general and
      powerful mechanism for engineering novel materials.

PMID- 25870302
TI  - HCN channels enhance spike phase coherence and regulate the phase of spikes and
      LFPs in the theta-frequency range.
AB  - What are the implications for the existence of subthreshold ion channels, their
      localization profiles, and plasticity on local field potentials (LFPs)? Here, we
      assessed the role of hyperpolarization-activated cyclic-nucleotide-gated (HCN)
      channels in altering hippocampal theta-frequency LFPs and the associated spike
      phase. We presented spatiotemporally randomized, balanced theta-modulated
      excitatory and inhibitory inputs to somatically aligned, morphologically
      realistic pyramidal neuron models spread across a cylindrical neuropil. We
      computed LFPs from seven electrode sites and found that the insertion of an
      experimentally constrained HCN-conductance gradient into these neurons introduced
      a location-dependent lead in the LFP phase without significantly altering its
      amplitude. Further, neurons fired action potentials at a specific theta phase of
      the LFP, and the insertion of HCN channels introduced large lags in this spike
      phase and a striking enhancement in neuronal spike-phase coherence. Importantly,
      graded changes in either HCN conductance or its half-maximal activation voltage
      resulted in graded changes in LFP and spike phases. Our conclusions on the impact
      of HCN channels on LFPs and spike phase were invariant to changes in neuropil
      size, to morphological heterogeneity, to excitatory or inhibitory synaptic
      scaling, and to shifts in the onset phase of inhibitory inputs. Finally, we
      selectively abolished the inductive lead in the impedance phase introduced by HCN
      channels without altering neuronal excitability and found that this inductive
      phase lead contributed significantly to changes in LFP and spike phase. Our
      results uncover specific roles for HCN channels and their plasticity in phase
      coding schemas and in the formation and dynamic reconfiguration of neuronal cell
      assemblies. 

PMID- 25870303
TI  - Self-aligned deterministic coupling of single quantum emitter to nanofocused
      plasmonic modes.
AB  - The quantum plasmonics field has emerged and been growing increasingly, including
      study of single emitter-light coupling using plasmonic system and scalable
      quantum plasmonic circuit. This offers opportunity for the quantum control of
      light with compact device footprint. However, coupling of a single emitter to
      highly localized plasmonic mode with nanoscale precision remains an important
      challenge. Today, the spatial overlap between metallic structure and single
      emitter mostly relies either on chance or on advanced nanopositioning control.
      Here, we demonstrate deterministic coupling between three-dimensionally
      nanofocused plasmonic modes and single quantum dots (QDs) without any positioning
      for single QDs. By depositing a thin silver layer on a site-controlled pyramid QD
      wafer, three-dimensional plasmonic nanofocusing on each QD at the pyramid apex is
      geometrically achieved through the silver-coated pyramid facets. Enhancement of
      the QD spontaneous emission rate as high as 22 +/- 16 is measured for all
      processed QDs emitting over ~150-meV spectral range. This approach could apply to
      high fabrication yield on-chip devices for wide application fields, e.g., high
      efficiency light-emitting devices and quantum information processing. 

PMID- 25870304
TI  - Nanoparticle self-assembly at the interface of liquid crystal droplets.
AB  - Nanoparticles adsorbed at the interface of nematic liquid crystals are known to
      form ordered structures whose morphology depends on the orientation of the
      underlying nematic field. The origin of such structures is believed to result
      from an interplay between the liquid crystal orientation at the particles'
      surface, the orientation at the liquid crystal's air interface, and the bulk
      elasticity of the underlying liquid crystal. In this work, we consider
      nanoparticle assembly at the interface of nematic droplets. We present a
      systematic study of the free energy of nanoparticle-laden droplets in terms of
      experiments and a Landau-de Gennes formalism. The results of that study indicate
      that, even for conditions under which particles interact only weakly at flat
      interfaces, particles aggregate at the poles of bipolar droplets and assemble
      into robust, quantized arrangements that can be mapped onto hexagonal lattices.
      The contributions of elasticity and interfacial energy corresponding to different
      arrangements are used to explain the resulting morphologies, and the predictions
      of the model are shown to be consistent with experimental observations. The
      findings presented here suggest that particle-laden liquid crystal droplets could
      provide a unique and versatile route toward building blocks for hierarchical
      materials assembly. 

PMID- 25870305
TI  - Defining the loop structures in proteins based on composite beta-turn mimics.
AB  - Asx- and omega-turns are beta-turn mimics, which replace the conventional main
      chain hydrogen bonds seen in the latter by those involving the side chains, and
      both involve three residues. In this paper we analyzed the cases where these
      turns occur together--side by side, with or without any gap, overlapping and in
      any order. These composite turns (of length 3-15 residues), occurring at ~1 per
      100 residues, may constitute the full length of many loops, and when the residues
      in the two component turns overlap or are adjacent to each other, the composite
      may take well-defined shape. It is thus possible for non-regular regions in
      protein structure to form local structural motifs, akin to the regular
      geometrical features exhibited by secondary structures. Composites having the
      order omega-turns followed by Asx-turns can constitute N-terminal helix capping
      motif. Ternary composite turns (made up of omega-, Asx- and ST-turns), some with
      characteristic shape, have also been identified. Delineation of composite turns
      would help in characterizing loops in protein structures, which often have
      functional roles. Some sequence patterns seen in composites can be used for their
      incorporation in protein design.

PMID- 25870307
TI  - Tough luck and tough choices: applying luck egalitarianism to oral health.
AB  - Luck egalitarianism is often taken to task for its alleged harsh implications.
      For example, it may seem to imply a policy of nonassistance toward uninsured
      reckless drivers who suffer injuries. Luck egalitarians respond to such
      objections partly by pointing to a number of factors pertaining to the cases
      being debated, which suggests that their stance is less inattentive to the plight
      of the victims than it might seem at first. However, the strategy leaves some
      cases in which the attribution of individual responsibility is appropriate (and
      so, it seems, is asking people to pick up the tab for their choices). One such
      case is oral health or significant aspects of this. It is appropriate, the paper
      argues, to hold people responsible for a number of factors that affect their oral
      health. A luck egalitarian approach inspired by John Roemer can assess whether
      people have acted responsibly by comparing their choices to those of their peers.
      A luck egalitarian approach to oral health would recommend prioritizing scarce
      resources in a responsibility-weighted queuing system and include copayment and
      general taxation among its measures of financing. 

PMID- 25870308
TI  - The importance of amicable and productive disagreement.

PMID- 25870310
TI  - Needle tract pulmonary metastases.

PMID- 25870311
TI  - Are the antimicrobial properties of macrolides required for their therapeutic
      efficacy in chronic neutrophilic airway diseases?

PMID- 25870306
TI  - RNA Sequencing and Analysis.
AB  - RNA sequencing (RNA-Seq) uses the capabilities of high-throughput sequencing
      methods to provide insight into the transcriptome of a cell. Compared to previous
      Sanger sequencing- and microarray-based methods, RNA-Seq provides far higher
      coverage and greater resolution of the dynamic nature of the transcriptome.
      Beyond quantifying gene expression, the data generated by RNA-Seq facilitate the
      discovery of novel transcripts, identification of alternatively spliced genes,
      and detection of allele-specific expression. Recent advances in the RNA-Seq
      workflow, from sample preparation to library construction to data analysis, have
      enabled researchers to further elucidate the functional complexity of the
      transcription. In addition to polyadenylated messenger RNA (mRNA) transcripts,
      RNA-Seq can be applied to investigate different populations of RNA, including
      total RNA, pre-mRNA, and noncoding RNA, such as microRNA and long ncRNA. This
      article provides an introduction to RNA-Seq methods, including applications,
      experimental design, and technical challenges. 

PMID- 25870313
TI  - Correction.

PMID- 25870315
TI  - Does subclinical inflammation contribute to impairment of function of knee joints
      in aged individuals? High prevalence of ultrasound inflammatory findings.
AB  - OBJECTIVES: To investigate the prevalence of knee US findings of inflammation and
      structural damage in aged individuals (>=60 years) of a long-term population
      based cohort and to correlate these findings with demographic, clinical and
      laboratory parameters. METHODS: Cross-sectional clinical and US investigation of
      both knee joints during the 2010 follow-up of the prospective population-based
      Bruneck Study. Demographic variables, physical activity, comorbidities,
      medications, pain, and functional scales related to the knee joints were
      recorded. US-assessed parameters were synovial hypertrophy, power Doppler signal,
      joint effusion, cartilage abnormalities, osteophytes, enthesopathy and bursitis.
      Statistics included univariate and multivariate regression analysis. RESULTS: A
      total of 488 subjects (mean age 72.5 years; 53.5% females, 46.5% males) were
      examined by clinical assessment, and 433 of these underwent US examination of
      both knees. Both inflammatory and structural abnormalities were found in 296
      (68.8%) subjects. Inflammatory abnormalities were significantly associated with
      age in years, male gender, diabetes and the presence of knee joint symptoms. In
      the multivariate analysis, age, male gender and knee swelling emerged as
      independent predictors of inflammation [odds ratio (OR) (95% CI) = 1.06 (1.03,
      1.09), 2.55 (1.55, 4.21) and 5.92 (1.99, 17.58), respectively]. CONCLUSION: The
      present study showed a high prevalence of US inflammatory abnormalities in the
      knee joints of a normal aged population. These data suggest a substantial
      contribution of inflammation in progressive impairment of joint function with
      age.

PMID- 25870316
TI  - Ethosuximide Reduces Mortality and Seizure Severity in Response to
      Pentylenetetrazole Treatment During Ethanol Withdrawal.
AB  - AIMS: We recently demonstrated that T-type calcium channels are affected by
      alcohol abuse and withdrawal. Treatment with ethosuximide, an antiepileptic drug
      that blocks T-type calcium channels, reduces seizure activity induced by
      intermittent ethanol exposures and withdrawals. Here, we expand on these findings
      to test whether ethosuximide can reduce the sensitivity to pentylenetetrazole
      induced seizures during ethanol withdrawal. METHODS: We used an intermittent
      ethanol exposure model to produce withdrawal-induced hyperexcitability in DBA/2J
      mice. RESULTS: Ethosuximide (250 mg/kg) reduced seizure severity in mice
      undergoing ethanol withdrawal with concurrent PTZ treatment (20 mg/kg).
      Importantly, ethosuximide did not produce rebound excitability and protected
      against ethanol withdrawal-induced mortality produced by concurrent PTZ treatment
      (40 mg/kg). CONCLUSION: These results, in addition to previous preclinical
      findings, suggest that ethosuximide should be further evaluated as a safe,
      effective alternative to benzodiazepines for the treatment of alcohol withdrawal.

PMID- 25870317
TI  - British Thoracic Society guidelines for home oxygen use in adults.
AB  - The British Thoracic Society (BTS) Home Oxygen Guideline provides detailed
      evidence-based guidance for the use of home oxygen for patients out of hospital.
      Although the majority of evidence comes from the use of oxygen in patients with
      chronic obstructive pulmonary disease, the scope of the guidance includes
      patients with a variety of long-term respiratory illnesses and other groups in
      whom oxygen is currently ordered, such as those with cardiac failure, cancer and
      end-stage cardiorespiratory disease, terminal illness or cluster headache. It
      explores the evidence base for the use of different modalities of oxygen therapy
      and patient-related outcomes such as mortality, symptoms and quality of life. The
      guideline also makes recommendations for assessment and follow-up protocols, and
      risk assessments, particularly in the clinically challenging area of home oxygen
      users who smoke. The guideline development group is aware of the potential for
      confusion sometimes caused by the current nomenclature for different types of
      home oxygen, and rather than renaming them, has adopted the approach of
      clarifying those definitions, and in particular emphasising what is meant by long
      term oxygen therapy and palliative oxygen therapy. The home oxygen guideline
      provides expert consensus opinion in areas where clinical evidence is lacking,
      and seeks to deliver improved prescribing practice, leading to improved
      compliance and improved patient outcomes, with consequent increased value to the
      health service. 

PMID- 25870318
TI  - Endoplasmic Reticulum Stress and Store-Operated Calcium Entry Contribute to Usnic
      Acid-Induced Toxicity in Hepatic Cells.
AB  - The use of usnic acid as a weight loss agent is a safety concern due to reports
      of acute liver failure in humans. Previously we demonstrated that usnic acid
      induces apoptosis and cytotoxicity in hepatic HepG2 cells. We also demonstrated
      that usnic acid induces autophagy as a survival mechanism against its
      cytotoxicity. In this study, we investigated and characterized further molecular
      mechanisms underlying the toxicity of usnic acid in HepG2 cells. We found that
      usnic acid causes endoplasmic reticulum (ER) stress demonstrated by the increased
      expression of typical ER stress markers, including CHOP, ATF-4, p-eIF2alpha, and
      spliced XBP1. Usnic acid inhibited the secretion of Gaussia luciferase measured
      by an ER stress reporter assay. An ER stress inhibitor 4-phenylbutyrate
      attenuated usnic acid-induced apoptosis. Moreover, usnic acid significantly
      increased the cytosolic free Ca(2+) concentration. Usnic acid increased the
      expression of calcium release-activated calcium channel protein 1 (CRAM1 or
      ORAI1) and stromal interaction molecule 1, two key components of store-operated
      calcium entry (SOCE), which is the major Ca(2+) influx pathway in non-excitable
      cells, this finding was also confirmed in primary rat hepatocytes. Furthermore,
      knockdown of ORAI1 prevented ER stress and ATP depletion in response to usnic
      acid. In contrast, overexpression of ORAI1 increased ER stress and ATP depletion
      caused by usnic acid. Taken together, our results suggest that usnic acid
      disturbs calcium homeostasis, induces ER stress, and that usnic acid-induced
      cellular damage occurs at least partially via activation of the Ca(2+) channel of
      SOCE. 

PMID- 25870319
TI  - NOS-2 Inhibition in Phosgene-Induced Acute Lung Injury.
AB  - Phosgene exposure via an industrial or warfare release produces severe acute lung
      injury (ALI) with high mortality, characterized by massive pulmonary edema,
      disruption of epithelial tight junctions, surfactant dysfunction, and oxidative
      stress. There are no targeted treatments for phosgene-induced ALI. Previous
      studies demonstrated that nitric oxide synthase 2 (NOS-2) is upregulated in the
      lungs after phosgene exposure; however, the role of NOS-2 in the pathogenesis of
      phosgene-induced ALI remains unknown. We previously demonstrated that NOS-2
      expression in lung epithelium exacerbates inhaled endotoxin-induced ALI in mice,
      mediated partially through downregulation of surfactant protein B (SP-B)
      expression. Therefore, we hypothesized that a selective NOS-2 inhibitor delivered
      to the lung epithelium by inhalation would mitigate phosgene-induced ALI. Inhaled
      phosgene produced increases in bronchoalveolar lavage fluid protein, histologic
      lung injury, and lung NOS-2 expression at 24 h. Administration of the selective
      NOS-2 inhibitor 1400 W via inhalation, but not via systemic delivery,
      significantly attenuated phosgene-induced ALI and preserved epithelial barrier
      integrity. Furthermore, aerosolized 1400 W augmented expression of SP-B and
      prevented downregulation of tight junction protein zonula occludens 1 (ZO-1),
      both critical for maintenance of normal lung physiology and barrier integrity. We
      also demonstrate for the first time that NOS-2-derived nitric oxide downregulates
      the ZO-1 expression at the transcriptional level in human lung epithelial cells,
      providing a novel target for ameliorating vascular leak in ALI. Our data
      demonstrate that lung NOS-2 plays a critical role in the development of phosgene
      induced ALI and suggest that aerosolized NOS-2 inhibitors offer a novel
      therapeutic strategy for its treatment.

PMID- 25870320
TI  - Carbohydrate regulation of photosynthesis and respiration from branch girdling in
      four species of wet tropical rain forest trees.
AB  - How trees sense source-sink carbon balance remains unclear. One potential
      mechanism is a feedback from non-structural carbohydrates regulating
      photosynthesis and removing excess as waste respiration when the balance of
      photosynthesis against growth and metabolic activity changes. We tested this
      carbohydrate regulation of photosynthesis and respiration using branch girdling
      in four tree species in a wet tropical rainforest in Costa Rica. Because girdling
      severs phloem to stop carbohydrate export while leaving xylem intact to allow
      photosynthesis, we expected carbohydrates to accumulate in leaves to simulate a
      carbon imbalance. We varied girdling intensity by removing phloem in increments
      of one-quarter of the circumference (zero, one--quarter, half, three-quarters,
      full) and surrounded a target branch with fully girdled ones to create a gradient
      in leaf carbohydrate content. Light saturated photosynthesis rate was measured in
      situ, and foliar respiration rate and leaf carbohydrate content were measured
      after destructive harvest at the end of the treatment. Girdling intensity created
      no consistent or strong responses in leaf carbohydrates. Glucose and fructose
      slightly increased in all species by 3.4% per one-quarter girdle, total carbon
      content and leaf mass per area increased only in one species by 5.4 and 5.5% per
      one-quarter girdle, and starch did not change. Only full girdling lowered
      photosynthesis in three of four species by 59-69%, but the decrease in
      photosynthesis was unrelated to the increase in glucose and fructose content.
      Girdling did not affect respiration. The results suggest that leaf carbohydrate
      content remains relatively constant under carbon imbalance, and any changes are
      unlikely to regulate photosynthesis or respiration. Because girdling also stops
      the export of hormones and reactive oxygen species, girdling may induce
      physiological changes unrelated to carbohydrate accumulation and may not be an
      effective method to study carbohydrate feedback in leaves. In three species,
      removal of three-quarters of phloem area did not cause leaf carbohydrates to
      accumulate nor did it change photosynthesis or respiration, suggesting that
      phloem transport is flexible and transport rate per unit phloem can rapidly
      increase under an increase in carbohydrate supply relative to phloem area. Leaf
      carbohydrate content thus may be decoupled from whole plant carbon balance by
      phloem transport in some species, and carbohydrate regulation of photosynthesis
      and respiration may not be as common in trees as previous girdling studies
      suggest. Further studies in carbohydrate regulation should avoid using girdling
      as girdling can decrease photosynthesis through unintended means without the
      tested mechanisms of accumulating leaf carbohydrates. 

PMID- 25870322
TI  - Outbreak of Gastroenteritis in Adults Due to Rotavirus Genotype G12P[8].
AB  - BACKGROUND: Rotavirus infection in adults is poorly understood and few rotavirus
      outbreaks among US adults have been reported in the literature. We describe an
      outbreak due to genotype G12P[8] rotavirus among medical students, faculty, and
      guests who attended a formal dinner event in April 2013. METHODS: A web-based
      questionnaire was distributed to event attendees to collect symptom and exposure
      data. A clinical case was defined as a person who developed diarrhea after
      attending the formal event. A laboratory-confirmed case was defined as a clinical
      case who attended the formal event, with rotavirus detected in stool by enzyme
      immunoassay or reverse transcription-polymerase chain reaction (RT-PCR) assay.
      RESULTS: Among 334 dinner attendees, 136 (41%) completed the web-based
      questionnaire; 58 (43%) respondents reported illness. Symptom onset ranged from 1
      to 8 days, with peak onset 3 days after the event. In addition to diarrhea,
      predominant symptoms included fever (91%), abdominal pain (84%), and vomiting
      (49%). The median duration of illness was 2.5 days. Thirteen (22%) of 58 cases
      sought medical attention; none were hospitalized. Analysis of food exposures
      among questionnaire respondents did not identify significant associations between
      any specific food or drink item and illness. Stool specimens were negative for
      bacterial pathogens by culture and negative for norovirus by RT-PCR assay; 4
      specimens were positive for rotavirus by enzyme immunoassay or PCR. G12P[8]-R1-C1
      M1-A1-N1-T1-E1-H1 was identified as the causative full-genome genotype.
      CONCLUSIONS: Rotavirus outbreaks can occur among adults, including young adults.
      Health professionals should consider rotavirus as a cause of acute
      gastroenteritis in adults.

PMID- 25870323
TI  - Epidemiology and outcome of fungemia in a cancer Cohort of the Infectious
      Diseases Group (IDG) of the European Organization for Research and Treatment of
      Cancer (EORTC 65031).
AB  - BACKGROUND: Anti-cancer treatment and the cancer population have evolved since
      the last European Organisation for Research and Treatment of Cancer (EORTC)
      fungemia survey, and there are few recent large epidemiological studies. METHODS:
      This was a prospective cohort study including 145 030 admissions of patients with
      cancer from 13 EORTC centers. Incidence, clinical characteristics, and outcome of
      fungemia were analyzed. RESULTS: Fungemia occurred in 333 (0.23%; 95% confidence
      interval [CI], .21-.26) patients, ranging from 0.15% in patients with solid
      tumors to 1.55% in hematopoietic stem cell transplantation recipients. In 297
      evaluable patients age ranged from 17 to 88 years (median 56 years), 144 (48%)
      patients were female, 165 (56%) had solid tumors, and 140 (47%) had hematological
      malignancies. Fungemia including polymicrobial infection was due to: Candida spp.
      in 267 (90%), C. albicans in 128 (48%), and other Candida spp. in 145 (54%)
      patients. Favorable overall response was achieved in 113 (46.5%) patients by week
      2. After 4 weeks, the survival rate was 64% (95% CI, 59%-70%) and was not
      significantly different between Candida spp. Multivariable logistic regression
      identified baseline septic shock (odds ratio [OR] 3.04, 95% CI, 1.22-7.58) and
      tachypnoea as poor prognostic factors (OR 2.95, 95% CI, 1.66-5.24), while
      antifungal prophylaxis prior to fungemia (OR 0.20, 95% CI, .06-.62) and remission
      of underlying cancer (OR, 0.18; 95% CI, .06-.50) were protective. CONCLUSIONS:
      Fungemia, mostly due to Candida spp., was rare in cancer patients from EORTC
      centers but was associated with substantial mortality. Antifungal prophylaxis and
      remission of cancer predicted better survival.

PMID- 25870324
TI  - Safety and immunogenicity of a Vi polysaccharide-tetanus toxoid conjugate vaccine
      (Typbar-TCV) in healthy infants, children, and adults in typhoid endemic areas: a
      multicenter, 2-cohort, open-label, double-blind, randomized controlled phase 3
      study.
AB  - BACKGROUND: Enteric fever caused by Salmonella Typhi remains a major public
      health problem in developing countries. Typbar-TCV is a single-dose typhoid Vi
      polysaccharide-tetanus toxoid conjugate vaccine for persons >=6 months of age.
      METHODS: Six hundred fifty-four healthy subjects aged 2-45 years enrolled in a
      double-blind, randomized controlled trial (RCT) received a single dose of Typbar
      TCV or comparator "Vi polysaccharide" (Typbar), and 327 healthy subjects aged 6
      23 months received a single dose of Typbar-TCV in an open-label trial (OLT); both
      received single- or multidose presentations from different lots. After 2 years,
      subsets in each group received a booster dose. The primary objective included
      analysis of geometric mean titer (GMTs) and 4-fold rise of anti-Vi serum
      immunoglobulin G (IgG) enzyme-linked immunosorbent assay titers over baseline
      (seroconversion [SCN]) 42 days after immunization. RESULTS: Typbar-TCV recipients
      in the RCT attained higher anti-Vi IgG GMTs 42 days after immunization (SCN, 97%;
      GMT, 1293 [95% confidence interval {CI}, 1153-1449]) than recipients of Typbar
      (SCN, 93%; GMT, 411 [95% CI, 359-471]) (P < .001). Typbar-TCV was highly
      immunogenic in the OLT (SCN, 98%; GMT, 1937 [95% CI, 1785-2103]). Two years after
      vaccination, anti-Vi titers remained higher in Typbar-TCV subjects (GMT, 82 [95%
      CI, 73-92]); and exhibited higher avidity (geometric mean avidity index [GMAI],
      60%) than in Typbar recipients (GMT, 46 [95% CI, 40-53]; GMAI 46%) in the RCT (P
      < .001). OLT Typbar-TCV recipients achieved GMT of 48 (95% CI, 42-55) and GMAI of
      57%. Typbar-TCV induced multiple IgG subclasses and strong booster responses in
      all ages. No serious vaccine-attributable adverse events were observed.
      CONCLUSIONS: Single-dose Typbar-TCV is well tolerated and induces robust and long
      lasting serum anti-Vi IgG across age groups. CLINICAL TRIALS REGISTRATION:
      CTRI/2011/08/001957, CTRI/2014/01/004341.

PMID- 25870325
TI  - The lipid-lowering effect of tenofovir/emtricitabine: a randomized, crossover,
      double-blind, placebo-controlled trial.
AB  - BACKGROUND: It is unknown if tenofovir disoproxil fumarate (TDF), which is often
      coformulated with the lipid-neutral emtricitabine (FTC), has a lipid-lowering
      effect. METHODS: We performed a randomized, crossover, double-blind, placebo
      controlled clinical trial on human immunodeficiency virus type 1 (HIV-1)-infected
      subjects with HIV-1 RNA < 50 copies/mL during >=6 months on stable
      darunavir/ritonavir (800/100 mg once daily) or lopinavir/ritonavir (400/100 mg
      twice daily) monotherapy, fasting total cholesterol (TC) >=200 mg/dL or low
      density lipoprotein cholesterol (LDL-c) >=130 mg/dL, and no lipid-lowering drugs.
      In arm 1, TDF/FTC was added for 12 weeks, followed by 12 weeks of placebo
      (washout) and 12 additional weeks of placebo (placebo period). Subjects in arm 2
      added placebo for 12 weeks (placebo period) followed by TDF/FTC for 12 weeks and
      placebo for 12 additional weeks (washout). The primary endpoint was change in
      median fasting TC levels. RESULTS: Of 46 subjects enrolled, 56% received
      darunavir/ritonavir and 44% lopinavir/ritonavir. Exposure to TDF/FTC reduced TC
      from 234 to 205 mg/dL (P < .001), LDL-c from 155 to 128 mg/dL (P < .001), and
      high-density lipoprotein cholesterol (HDL-c) from 50.3 to 44.5 mg/dL (P < .001).
      It also decreased the proportion of subjects with fasting TC >=200 mg/dL from
      86.7% to 56.8% (P = .001), and LDL-c >=130 mg/dL from 87.8% to 43.9% (P < .001).
      After 12 weeks, TDF/FTC exposure was associated with lower TC and LDL-c levels
      than placebo (P = .001 and P = .002, respectively). The TC/HDL-c ratio and
      triglyceride levels did not change with TDF/FTC exposure. CONCLUSIONS:
      Coformulated TDF/FTC has an intrinsic lipid-lowering effect, likely attributable
      to TDF. CLINICAL TRIALS REGISTRATION: NCT01458977.

PMID- 25870326
TI  - Circulating biomarkers for discrimination between aseptic joint failure, low
      grade infection, and high-grade septic failure.
AB  - BACKGROUND: Late-onset chronic (low-grade) periprosthetic joint infections are
      often accompanied by unspecific symptoms, false-negative cultures or nonspecific
      low values of serum biomarkers. This may lead to the unintended implantation of a
      revision prosthesis into an infected surgical site with the risk of short-term
      failure developing again. Conversely, false diagnosis of joint infection may
      result in multistage revision procedures, which expose the patient to unnecessary
      surgical procedures and inappropriate antibiotic treatment. Here, we investigated
      whether circulating biomarkers can preoperatively distinguish between aseptic
      prosthesis loosening and low-grade joint infection, and which biomarker
      combinations are most accurate. METHODS: Inclusion criteria for the study were
      indication for revision arthroplasty due to aseptic implant failure, acute high
      grade infection, or (suspected) low-grade infection. C-reactive protein (CRP),
      procalcitonin, tumor necrosis factor alpha, interleukin 6 (IL-6), interleukin 10,
      and lipopolysaccharide binding protein were assessed preoperatively in the serum
      of 98 adult patients. RESULTS: The classification tree method revealed IL-6 and
      CRP as the most suitable biomarker combination for the discrimination of aseptic
      loosening vs low-grade joint infection. The combination of IL-6 >5.12 pg/mL and
      CRP >0.3 mg/dL correctly identified 15 of 16 patients as having low-grade
      infection (94%) whereas just one patient was aseptic (6%). CONCLUSIONS: This is
      the first comprehensive prospective clinical study to our knowledge investigating
      the significance of a combined biomarker approach in differentiating between
      aseptic prosthesis loosening and low-grade joint infection. CRP plus IL-6 seems
      to be the most helpful combination for preoperative discrimination of aseptic
      loosening vs low-grade joint infection.

PMID- 25870328
TI  - Review of fungal outbreaks and infection prevention in healthcare settings during
      construction and renovation.
AB  - Hospital construction and renovation activities are an ever-constant phenomenon
      in healthcare facilities, causing dust contamination and possible dispersal of
      fungal spores. We reviewed fungal outbreaks that occurred during construction and
      renovation over the last 4 decades as well as current infection prevention
      strategies and control measures. Fungal outbreaks still occur in healthcare
      settings, especially among patients with hematological malignancies and those who
      are immunocompromised. The causative pathogens of these outbreaks were usually
      Aspergillus species, but Zygomycetes and other fungi were occasionally reported.
      Aspergillus most commonly caused pulmonary infection. The overall mortality of
      construction/renovation-associated fungal infection was approximately 50%. The
      minimal concentration of fungal spores by air sampling for acquisition of fungal
      infections remains to be determined. Performing infection control risk
      assessments and implementing the recommended control measures is essential to
      prevent healthcare-associated fungal outbreaks during construction and
      renovation. 

PMID- 25870330
TI  - Dose optimization of raltegravir chewable tablets in a 4-year-old HIV-infected
      child.

PMID- 25870329
TI  - Immunogenicity, safety, and tolerability of 13-valent pneumococcal conjugate
      vaccine followed by 23-valent pneumococcal polysaccharide vaccine in recipients
      of allogeneic hematopoietic stem cell transplant aged >=2 years: an open-label
      study.
AB  - BACKGROUND: Life-threatening Streptococcus pneumoniae infections often occur
      after hematopoietic stem cell transplant (HSCT); vaccination is important for
      prevention. METHODS: In an open-label study, patients (n = 251) 3-6 months after
      allogeneic HSCT received 3 doses of 13-valent pneumococcal conjugate vaccine
      (PCV13) at 1-month intervals, a fourth dose 6 months later, and 1 dose of 23
      valent pneumococcal polysaccharide vaccine (PPSV23) 1 month later. Immunogenicity
      at prespecified time points and vaccine safety were assessed. RESULTS: In the
      evaluable immunogenicity population (N = 216; mean age, 37.8 years), geometric
      mean fold rises (GMFRs) of immunoglobulin G geometric mean concentrations from
      baseline to postdose 3 showed significant increases in antibody levels across all
      PCV13 serotypes (GMFR range, 2.99-23.85; 95% confidence interval lower limit,
      >1); there were significant declines over the next 6 months, significant
      increases from predose 4 to postdose 4 (GMFR range, 3.00-6.97), and little change
      after PPSV23 (GMFR range, 0.86-1.12). Local and systemic reactions were more
      frequent after dose 4. Six patients experienced serious adverse events possibly
      related to PCV13 (facial diplegia, injection-site erythema and pyrexia,
      autoimmune hemolytic anemia, and suspected lack of vaccine efficacy after dose 3
      leading to pneumococcal infection), PCV13 and PPSV23 (Guillain-Barre syndrome),
      or PPSV23 (cellulitis). There were 14 deaths, none related to study vaccines.
      CONCLUSIONS: A 3-dose PCV13 regimen followed by a booster dose may be required to
      protect against pneumococcal disease in HSCT recipients. Dose 4 was associated
      with increased local and systemic reactions, but the overall safety profile of a
      4-dose regimen was considered acceptable. CLINICAL TRIALS REGISTRATION:
      NCT00980655.

PMID- 25870332
TI  - Editorial commentary: uncoupling epidemiological synergy: new opportunities for
      HIV prevention for men who have sex with men.

PMID- 25870331
TI  - Histoplasmosis complicating tumor necrosis factor-alpha blocker therapy: a
      retrospective analysis of 98 cases.
AB  - BACKGROUND: Histoplasmosis may complicate tumor necrosis factor (TNF)-alpha
      blocker therapy. Published case series provide limited guidance on disease
      management. We sought to determine the need for long-term antifungal therapy and
      the safety of resuming TNF-alpha blocker therapy after successful treatment of
      histoplasmosis. METHODS: We conducted a multicenter retrospective review of 98
      patients diagnosed with histoplasmosis between January 2000 and June 2011.
      Multivariate logistic regression was used to evaluate risk factors for severe
      disease. RESULTS: The most commonly used biologic agent was infliximab (67.3%).
      Concomitant corticosteroid use (odds ratio [OR], 3.94 [95% confidence interval
      {CI}, 1.06-14.60]) and higher urine Histoplasma antigen levels (OR, 1.14 [95% CI,
      1.03-1.25]) were found to be independent predictors of severe disease. Forty-six
      (47.4%) patients were initially treated with an amphotericin B formulation for a
      median duration of 2 weeks. Azole treatment was given for a median of 12 months.
      TNF-alpha blocker therapy was initially discontinued in 95 of 98 (96.9%) patients
      and later resumed in 25 of 74 (33.8%) patients at a median of 12 months (range, 1
      69 months). The recurrence rate was 3.2% at a median follow-up period of 32
      months. Of the 3 patients with recurrence, 2 had restarted TNF-alpha blocker
      therapy, 1 of whom died. Mortality rate was 3.2%. CONCLUSIONS: In this study,
      disease outcomes were generally favorable. Discontinuation of antifungal
      treatment after clinical response and an appropriate duration of therapy,
      probably at least 12 months, appears safe if pharmacologic immunosuppression has
      been held. Resumption of TNF-alpha blocker therapy also appears safe, assuming
      that the initial antifungal therapy was administered for 12 months.

PMID- 25870333
TI  - The high risk of an HIV diagnosis following a diagnosis of syphilis: a population
      level analysis of New York City men.
AB  - BACKGROUND: Epidemiologic studies have shown that syphilis is associated with
      risk for human immunodeficiency virus (HIV) infection. We used population-level
      syphilis and HIV data to quantify HIV incidence among men following primary or
      secondary (P&S) syphilis diagnoses and identify the highest-risk subgroups for
      intensified prevention, such as pre-exposure prophylaxis with antiretroviral
      medications. METHODS: Male cases reported to the New York City HIV/AIDS and
      Sexually Transmitted Disease (STD) surveillance registries were matched using a
      deterministic algorithm. We measured HIV incidence following P&S syphilis
      diagnosed between 2000 and June 2010 and identified risk factors for HIV
      infection using Cox proportional hazards models. RESULTS: Of 2805 men with
      syphilis contributing 11 714 person-years of follow-up, 423 (15.1%) acquired HIV;
      annual incidence was 3.61% (95% confidence interval [CI], 3.27%, 3.97%). HIV
      incidence was high among: men who have sex with men (MSM) (5.56%, 95% CI, 5.02%
      6.13%); males with secondary compared with primary syphilis (4.10% vs 2.64%, P <
      .0001); and males diagnosed with another bacterial STD after syphilis (7.89%, 95%
      CI, 6.62%-9.24%). CONCLUSIONS: HIV incidence among men diagnosed with syphilis is
      high; one in 20 MSM were diagnosed with HIV within a year. Our data have
      implications for syphilis and HIV screening and may be useful for further
      targeting HIV-negative populations for pre-exposure prophylaxis.

PMID- 25870334
TI  - Desformylflustrabromine (dFBr) and [3H]dFBr-Labeled Binding Sites in a Nicotinic
      Acetylcholine Receptor.
AB  - Desformylflustrabromine (dFBr) is a positive allosteric modulator (PAM) of
      alpha4beta2 and alpha2beta2 nAChRs that, at concentrations >1 uM, also inhibits
      these receptors and alpha7 nAChRs. However, its interactions with muscle-type
      nAChRs have not been characterized, and the locations of its binding site(s) in
      any nAChR are not known. We report here that dFBr inhibits human muscle
      (alphabetaepsilondelta) and Torpedo (alphabetagammadelta) nAChR expressed in
      Xenopus oocytes with IC50 values of ~ 1 MUM. dFBr also inhibited the equilibrium
      binding of ion channel blockers to Torpedo nAChRs with higher affinity in the
      nAChR desensitized state ([(3)H]phencyclidine; IC50 = 4 MUM) than in the resting
      state ([(3)H]tetracaine; IC50 = 60 MUM), whereas it bound with only very low
      affinity to the ACh binding sites ([(3)H]ACh, IC50 = 1 mM). Upon irradiation at
      312 nm, [(3)H]dFBr photoincorporated into amino acids within the Torpedo nAChR
      ion channel with the efficiency of photoincorporation enhanced in the presence of
      agonist and the agonist-enhanced photolabeling inhibitable by phencyclidine. In
      the presence of agonist, [(3)H]dFBr also photolabeled amino acids in the nAChR
      extracellular domain within binding pockets identified previously for the
      nonselective nAChR PAMs galantamine and physostigmine at the canonical alpha
      gamma interface containing the transmitter binding sites and at the noncanonical
      delta-beta subunit interface. These results establish that dFBr inhibits muscle
      type nAChR by binding in the ion channel and that [(3)H]dFBr is a photoaffinity
      probe with broad amino acid side chain reactivity.

PMID- 25870335
TI  - Characteristics of ventricular tachycardia ablation in patients with continuous
      flow left ventricular assist devices.
AB  - BACKGROUND: Left ventricular assist devices (LVADs) are increasingly used as a
      bridge to cardiac transplantation or as destination therapy. Patients with LVADs
      are at high risk for ventricular arrhythmias. This study describes ventricular
      arrhythmia characteristics and ablation in patients implanted with a Heart Mate
      II device. METHODS AND RESULTS: All patients with a Heart Mate II device who
      underwent ventricular arrhythmia catheter ablation at 9 tertiary centers were
      included. Thirty-four patients (30 male, age 58+/-10 years) underwent 39 ablation
      procedures. The underlying cardiomyopathy pathogenesis was ischemic in 21 and
      nonischemic in 13 patients with a mean left ventricular ejection fraction of
      17%+/-5% before LVAD implantation. One hundred and ten ventricular tachycardias
      (VTs; cycle lengths, 230-740 ms, arrhythmic storm n=28) and 2 ventricular
      fibrillation triggers were targeted (25 transseptal, 14 retrograde aortic
      approaches). Nine patients required VT ablation <1 month after LVAD implantation
      because of intractable VT. Only 10/110 (9%) of the targeted VTs were related to
      the Heart Mate II cannula. During follow-up, 7 patients were transplanted and 10
      died. Of the remaining 17 patients, 13 were arrhythmia-free at 25+/-15 months. In
      1 patient with VT recurrence, change of turbine speed from 9400 to 9000 rpm
      extinguished VT. CONCLUSIONS: Catheter ablation of VT among LVAD recipients is
      feasible and reasonably safe even soon after LVAD implantation. Intrinsic
      myocardial scar, rather than the apical cannula, seems to be the dominant
      substrate.

PMID- 25870336
TI  - Biventricular repair in heterotaxy patients.
AB  - BACKGROUND: Heterotaxy patients' hearts may or may not be suitable for
      biventricular repair depending on anatomy. Even in the subset that are amenable
      to surgical septation, cardiac anatomy may present multiple difficulties in
      achieving a satisfactory repair. However, it is also well known that heterotaxy
      patients are not ideal candidates for univentricular repair. METHODS: From 2007
      until 2012, a total of 20 patients (11 male) with heterotaxy syndrome underwent
      biventricular repair (left atrial isomerism: 10 and right atrial isomerism: 10)
      in our center. Their median age at surgery was 40 (range: 3-108) months. Ten
      patients had dextrocardia. Eleven patients presented with bilateral superior vena
      cava, three with inferior vena cava (IVC) draining into left atrium, and six with
      IVC interruption with azygos or hemiazygos continuation. Anomalous pulmonary
      venous drainage was present in eight patients. One had a common atrium.
      Atrioventricular septal defect (AVSD) occurred in nine (complete AVSD in seven)
      patients. Eight patients had double outlet right ventricle (DORV), one had d
      transposition of great arteries (d-TGA), and two had congenitally corrected
      transposition of the great arteries (CC-TGA). Prior palliative procedures
      included pulmonary artery banding in three patients and left modified Blalock
      Taussig shunt in one patient. Complex intra-atrial baffle constructions were
      required in all patients to direct pulmonary and systemic venous inflow to the
      appropriate ventricle. Complete AVSDs were corrected using two-patch technique.
      Intraventricular tunnel repair was done for DORV. Combined atrial and arterial
      switch was required to rectify abnormal connections in a child with congenitally
      corrected transposition with normal pulmonary valve, while a Rastelli + Senning
      was needed in two children with CC-TGA with pulmonary atresia (n = 1) and double
      outlet of the right ventricle (n = 1). RESULTS: Major early postoperative
      complications included intestinal gangrene in four patients for which they
      underwent bowel resection. Two of these patients could not be salvaged. One
      patient required coiling of aortopulmonary collateral for early postoperative
      pulmonary hemorrhage. Two patients needed a tracheostomy for prolonged mechanical
      ventilatory support. Five patients had a pacemaker implanted for complete heart
      block. There were no instances of atrial baffle stenosis. Median follow-up was 27
      (range: 2-46) months. There was one late death secondary to pneumonia.
      CONCLUSIONS: Satisfactory survival outcomes can be achieved in heterotaxy
      patients who undergo hemodynamically acceptable biventricular repair. Borderline
      ventricular hypoplasia and trivial atrioventricular valve regurgitation should
      not be considered as discouraging factors in anatomically suitable heterotaxy
      patients as it is possible to adopt a two-stage repair in such patients to
      achieve biventricular repair at a later stage. Anticipating a higher incidence of
      conduction problems and gut malrotation preemptively can help reduce the
      morbidity.

PMID- 25870337
TI  - Invited commentary: biventricular repair in heterotaxy patients.

PMID- 25870338
TI  - Abdominal cardiac devices in pediatric and congenital heart disease: a practice
      model transition.
AB  - BACKGROUND: Abdominal cardiac implantable electronic device maintenance
      procedures are traditionally performed by cardiac surgeons. The University of
      Michigan Congenital Heart Center transitioned from this practice model to one in
      which electrophysiologists perform the majority of these procedures. This study
      presents the outcomes of these procedures during this transition. METHODS:
      Retrospective cohort study of all patients undergoing abdominal device
      maintenance procedure, inclusive of generator change, removal, or placement with
      preexisting leads from January 2005 to July 2013. Procedures involving epicardial
      lead placement were excluded. The primary outcome was major complications defined
      as any intraoperative complication, the requirement of an additional operative
      intervention, or hospitalization for device-related infection. RESULTS: There
      were 113 procedures on 93 patients. Of these, 84 (74%) procedures were on
      patients with congenital heart disease. Cardiac surgeons performed 54 (48%)
      procedures and electrophysiologists performed 59 (52%). Mean age was 16 +/- 11
      years. The groups were similar regarding age and proportion with congenital heart
      disease (CHD). Major complications occurred in 3 (5.5%) cardiac surgeon
      procedures and 2 (3.4%) electrophysiologist procedures. There is no difference in
      the risk of major complications between groups (P = .59). CONCLUSION: This 8.5
      year period encompassed a practice model transition from cardiac surgeon
      performed abdominal device procedures to primarily electrophysiologist-performed
      abdominal device procedures. There was no difference in the risk of complications
      between services. This suggests that electrophysiologist-performed abdominal
      cardiac device maintenance procedures are a viable practice model, provided there
      is support and collaboration from the cardiac surgery service.

PMID- 25870339
TI  - Doppler-derived flow pattern in the descending aorta does not predict systemic to
      pulmonary arterial collateral flow in patients with single ventricle palliation:
      a cross-sectional study.
AB  - BACKGROUND: Children with single ventricle heart disease are at risk for
      developing systemic to pulmonary arterial collateral vessels that adversely
      impact short-term outcomes, although the effect on long-term outcomes remains
      unclear. Collateral flow (CollF) can be quantified using cardiac magnetic
      resonance (CMR) flow quantification. The velocity-time integral (VTI), obtained
      from spectral Doppler tracings, has been used in "runoff" lesions like aortic
      regurgitation to quantify insufficiency. We hypothesized that the VTI ratio of
      the proximal descending aorta (DAo) after cavopulmonary anastomosis (CPA) would
      estimate CollF. METHODS: A retrospective cross-sectional study was conducted.
      Patients who had a superior CPA or total CPA and underwent CMR between April 2008
      and December 2012 were included. Those with greater than trivial semilunar valve
      insufficiency or aortic arch obstruction were excluded. In a subset (n = 88),
      spectral Doppler tracings of the DAo were analyzed to determine the VTI ratio. In
      another subset (n = 112), CMR was used to determine the ratio of retrograde to
      antegrade flow in the DAo. RESULTS: There was no linear correlation between VTI
      ratio and CollF (r (2) = .006, P = .46). There was a weakly positive correlation
      with CollF (r (2) = .07, P = .007) and the CMR measured ratio of retrograde to
      antegrade flow. Holodiastolic flow reversal by echo did not predict higher CollF
      (P = .40), but those with holodiastolic flow reversal by CMR had significantly
      higher CollF (P = .04). CONCLUSIONS: The ratio of reverse to forward flow in the
      DAo as determined by Doppler echo does not accurately reflect CollF in children
      with single ventricle after CPA.

PMID- 25870340
TI  - Pediatric cardiac tumors: a 45-year, single-institution review.
AB  - BACKGROUND: Cardiac tumors in children are rare. Of the cases reported in the
      literature, nearly all are benign and managed conservatively. METHODS: This is a
      retrospective, observational study of pediatric patients <18 years who presented
      for surgical evaluation of a cardiac tumor, between 1969 and 2014 at a tertiary
      care children's hospital. Presentation, pathology, management, and outcomes were
      evaluated. RESULTS: Over the last 45 years, 64 patients were evaluated for
      surgical resection of a cardiac tumor. Rhabdomyoma was the most common neoplasm
      (58%), and 17% of the tumors had malignant pathologies. While 42% of benign
      cardiac neoplasms required surgical intervention for significant hemodynamic
      concerns, 73% of malignant neoplasms underwent radical excision, if possible,
      followed by adjuvant chemotherapy. Despite a 37% mortality in patients with
      malignant pathology, an aggressive surgical approach can yield long-term survival
      in some patients. There were no deaths among patients with benign tumors and 17%
      had postoperative complications mostly related to mitral regurgitation.
      CONCLUSION: Cardiac tumors in children are rare but can be managed aggressively
      with good outcomes. Benign tumors have an excellent survival with most
      complications related to tumor location. Malignant tumors have a high mortality
      rate, but surgery and adjuvant chemotherapy allow for prolonged survival in
      selected patients.

PMID- 25870341
TI  - Outcome following augmentation of superior cavopulmonary blood flow with an
      arteriovenous fistula.
AB  - BACKGROUND: Axillary or brachial arteriovenous fistulae are occasionally created
      to improve systemic oxygen saturation in patients with functionally
      univentricular circulation after superior cavopulmonary anastomosis. Different
      techniques of fistula construction may account for the conflicting results. We
      sought to determine the impact of axillary arteriovenous fistula on systemic
      oxygen saturation and survival before subsequent palliation or heart
      transplantation. METHODS: Medical records of patients who underwent a side-to
      side anastomosis between an adjacent axillary artery and vein for cyanosis after
      superior cavopulmonary anastomosis between 1991 and 2010 were reviewed. RESULTS:
      The median age (n = 23) at the time of fistula creation was 54 months (4-278
      months). There was no operative mortality. The median duration of fistula patency
      was 48 months (1-174 months). Oxygen saturation improved from 71% +/- 10%
      preoperatively to 84% +/- 4% early (P < .05) and 81% +/- 4% long term after the
      arteriovenous fistula (P < .05). Twelve patients underwent additional surgery
      (total cavopulmonary anastomosis 6, partial biventricular repair 2, and heart
      transplantation 4) after an interval of 10 to 141 months. Six patients are alive
      with a patent fistula without subsequent interventions after an interval of 48 to
      174 months. Two patients with spontaneous closure or device closure of the
      fistula are alive after an interval of 76 to 80 months without subsequent
      interventions. Three deaths occurred with a patent fistula without subsequent
      interventions after an interval of 1 to 84 months. CONCLUSIONS: Systemic oxygen
      saturation improved with creation of an axillary arteriovenous fistula after
      superior cavopulmonary anastomosis. The fistula extended the duration of this
      stage of palliation without precluding the option for additional palliation or
      heart transplantation.

PMID- 25870342
TI  - Personal glimpses into the evolution of truncus arteriosus repair.
AB  - Truncus arteriosus (common arterial trunk) is an uncommon but complex congenital
      heart anomaly. Until the early 1970s, typically, patients died between the age of
      a few weeks to six months. Congestive heart failure owing to large pulmonary
      blood flow and truncal valve regurgitation was the major cause of death until
      innovative surgical techniques were discovered. In 1963, Herbert Sloan at the
      University of Michigan completed the first repair using a nonvalved conduit with
      long-term survival (not reported until 1974). At the Mayo Clinic, Rastelli and
      McGoon studied and completed the first repair with a valved homograft in 1967. In
      1976, Ebert used the 12-mm Hancock valved conduit in infants under six months of
      age (University of California, San Francisco). In Boston (mid-1980s), Jonas and
      Castaneda used aortic homografts, which greatly reduced bleeding as a
      postoperative complication. In the early 1990s, Bove (University of Michigan)
      reported outstanding results with an approach based on primary repair within the
      first few days of life for patients with truncus arteriosus. Improved prognosis
      for patients with truncus arteriosus resulted from these corrective operations by
      analyzing the natural history of this condition while applying innovative ideas,
      improved technology, and perioperative care.

PMID- 25870343
TI  - Understanding the morphology of the specialized conduction tissues in
      congenitally malformed hearts.
AB  - To repair congenital heart defects by means of open heart surgery, the surgeon
      needs guidance about the location and distribution of the specialized conduction
      tissues, in order to avoid their direct damage and consequent conduction
      disturbances. This review addresses the historical steps of the morphological
      study of the conduction system in different types of heart defects, providing
      updated information about the subject. 

PMID- 25870344
TI  - Catheter interventions for mitral stenosis in children: results and perspectives.
AB  - Stenosis of the mitral valve most often occurs as a result of chronic rheumatic
      heart disease, causing thickening and fibrosis of the mitral valve apparatus.
      Rheumatic heart disease continues to be a major public health problem in several
      developing countries and mitral stenosis is also common in these regions.
      According to the reports from India and Africa, the disease tends to follow a
      rapidly progressive course in children. The treatment of choice is balloon
      dilatation of the mitral valve. Echocardiography is indispensable for this
      procedure. Before planning the procedure, it is essential to assess the
      suitability of balloon dilatation. Echocardiography performed during the
      procedure helps to decide whether the size of the balloon needs to be increased
      in case of inadequate relief of stenosis. Most published series have reported an
      immediate success rate of over 90% with balloon dilatation in children and young
      adults. With an increase in mitral valve area and improvement in functional
      class, the left atrial pressure and the transmitral gradients fall. These
      gratifying results are also reported from very young children of less than 12
      years of age. It is recommended to start with a smaller balloon size and increase
      its size in a stepwise fashion to minimize complications. The complications, seen
      in about 1% to 2% of cases, include development of significant mitral
      regurgitation and hemopericardium, secondary to cardiac chamber perforation. The
      long-term results indicate slightly higher restenosis rates in children than in
      adults. Most children with restenosis can undergo successful repeat dilatation. 

PMID- 25870345
TI  - Recurrent coarctation: interventional techniques and results.
AB  - Coarctation of the aorta (CoA) accounts for 5% to 8% of all congenital heart
      defects. With all forms of interventions for native CoA, repeat intervention may
      be required due to restenosis and/or aneurysm formation. Restenosis rates vary
      from 5% to 24% and are higher in infants and children and in those with arch
      hypoplasia. Although repeat surgery can be done for recurrent CoA, guidelines
      from a number of professional societies have recommended balloon angioplasty with
      or without stenting as the preferred intervention for patients with isolated
      recoarctation. For infants and young children with recurrent coarctation, balloon
      angioplasty has been shown to be safe and effective with low incidence of
      complications. However, the rates of restenosis and reinterventions are high with
      balloon angioplasty alone. Endovascular stent placement is indicated, either
      electively in adults or as a bailout procedure in those who develop a
      complication such as dissection or intimal tear after balloon angioplasty.
      Conventionally bare metal stents are used; these can be dilated later if
      required. Covered stents, introduced more recently, are best reserved for those
      who have aneurysm at the site of previous repair or who develop a complication
      such as aortic wall perforation or tear. Stents produce complete abolition of
      gradients across the coarct segment in a majority of cases with good opening of
      the lumen on angiography. The long-term results are better than that of balloon
      angioplasty alone, with very low rates of restenosis. However, endovascular
      stenting is a technically demanding procedure and can be associated with serious
      complications rarely.

PMID- 25870346
TI  - The role of home monitoring in interstage management of infants following the
      Norwood procedure.
AB  - Although outcomes for infants with complex single ventricle heart defects have
      steadily improved in recent decades, there is still a significant risk for
      mortality and morbidity during the interstage period between stage 1 Norwood
      hospitalization discharge and stage 2 palliation. Home monitoring programs, which
      involve parental surveillance of daily weight and oxygen saturations during the
      interstage period, have been shown to significantly improve survival rates. This
      article describes the potential risk factors or causes of interstage mortality
      and reviews the role of home monitoring in early detection and potential
      prevention of adverse outcomes.

PMID- 25870347
TI  - Pediatric cardiac surgery in low- and middle-income countries or emerging
      economies: a continuing challenge.
AB  - A number of recent publications, addresses, seminars, and conferences have
      addressed the global backlog and increasing incidence of both congenital and
      acquired cardiac diseases in children, with reference to early and delayed
      recognition, late referral, availability of and access to services, costs, risks,
      databases, and early and long-term results and follow-up. A variety of proposals,
      recommendations, and projects have been outlined and documented. The ultimate
      goal of these endeavors is to increase the quality and quantity of pediatric
      cardiac care and surgery worldwide and particularly in underserved areas. A
      contemporary review of past and present initiatives is presented with a
      subsequent focus on the more challenging areas. 

PMID- 25870348
TI  - "How to do it": hybrid stent placement for pulmonary vein stenosis.
AB  - Pulmonary vein stenosis (PVS) is often progressive and severe. Surgical and
      percutaneous angioplasty are acutely successful; however, restenosis is common
      and many patients require multiple reinterventions. We perform intraoperative
      "hybrid" stent placement to deliver larger, stronger stents. Hybrid stent
      placement is well described for pulmonary arterial stenosis (PAS). The PAS data
      demonstrate that smaller stents are associated with rapid in-stent restenosis.
      Data from PVS in adults demonstrate superior outcomes with larger stents. Hybrid
      stent placement requires a strong collaborative effort between congenital heart
      surgeons and interventional cardiologists. 

PMID- 25870349
TI  - Endovascular treatment of superior vena cava obstruction after surgical
      correction of intracardiac total anomalous pulmonary venous connection.
AB  - A three-month-old infant operated for obstructed intracardiac total anomalous
      pulmonary venous connection was readmitted because of sinus bradycardia and
      superior vena cava syndrome. Cardiac catheterization revealed a stenosis at the
      superior vena cava-right atrial junction with retrograde azygos flow. Following
      balloon dilatation of the stenotic area and stent implantation, the superior vena
      cava syndrome was rapidly relieved. At six months, an echocardiogram confirmed
      unobstructed flow from the superior vena cava to the right atrium. 

PMID- 25870350
TI  - Masquerading acidosis after cardiopulmonary bypass: a case of propionic acidemia
      and congenital heart disease.
AB  - We report the case of a child with both propionic acidemia and cyanotic
      congenital heart disease. The presence of an underlying inborn error of
      metabolism confounded the management of this patient in the postoperative period,
      resulting in therapeutic misdirection until the true etiology of hyperlactemia
      was recognized.

PMID- 25870351
TI  - Repair of early posttransplant endomyocardial biopsy-related tricuspid
      regurgitation in a child.
AB  - We describe surgical repair of symptomatic tricuspid valve regurgitation in the
      early posttransplant period in a small child. The tricuspid valve regurgitation
      was due to injury to the valve and chordal apparatus during surveillance
      endomyocardial biopsy. The described surgical technique produced durable
      improvement in valve function. 

PMID- 25870352
TI  - Isolated right subclavian artery with interrupted aortic arch, ventricular septal
      defect, and left ventricular outflow tract obstruction.
AB  - We present two cases of isolated right subclavian artery from the right pulmonary
      artery (PA) associated with interrupted aortic arch, ventricular septal defect,
      left ventricular outflow tract obstruction, and 22q11 microdeletion. Both
      patients were successfully managed with bilateral PA banding initially followed
      by a modified Yasui operation. Isolation of the subclavian artery is rare but
      should always be taken into account, especially when bilateral PA banding is
      considered. The banding must then be placed on the PA distal to the origin of the
      subclavian artery. 

PMID- 25870353
TI  - Atypical pulmonary venous drainage pathway associated with infracardiac total
      anomalous pulmonary venous connection: report of a case.
AB  - Darling's classification for total anomalous pulmonary venous connection (TAPVC)
      is based only on the level of the site of drainage of the anomalous pulmonary
      veins (PVs) to the systemic venous circulation. Although it is a clinically
      useful classification, atypical course of the PVs is occasionally encountered as
      well. We report a case of infracardiac-type TAPVC in which the left upper PV
      traversed the posterior mediastinum and merged into the right PVs at the right
      hilum. The combined vein coursed medially and caudally, meeting the left lower
      PVs, and finally penetrated the diaphragm; the pulmonary venous drainage formed a
      shape of "C." Despite definitive diagnosis according to Darling's classification,
      sometimes atypical course of the PVs do exist. Echocardiography may not be
      adequate for atypical cases. Contrast-enhanced computed tomography may be
      recommended in stable patients where an atypical course is suspected.

PMID- 25870354
TI  - Intraoperative air embolism originating from a pulmonary vein.
AB  - Air embolism entering the systemic arterial system originating from the pulmonary
      circuit itself is an extremely rare occurrence. We report the case of an 18-year
      old female undergoing correction of an atrial septal defect, who had an air
      embolism that is believed to have originated from the right superior pulmonary
      vein. Although the exact mechanism of air entry remains a matter of speculation,
      several plausible hypotheses are proposed and discussed. Injury to a pulmonary
      vein may lead to air entry with migration to the left atrium and ultimately to
      systemic embolism. 

PMID- 25870355
TI  - Biventricular repair in a neonate with obstructive inflow cardiac rhabdomyoma and
      tuberous sclerosis.
AB  - A neonate with prenatally diagnosed large intracardiac rhabdomyomas and suspicion
      of tuberous sclerosis presented at birth with severe ductal-dependent obstruction
      at the tricuspid valve and an atrial septal defect (ASD). Biventricular repair at
      9 days of life included tumor resection, repair of the posterior leaflet of the
      tricuspid valve with autologous pericardium, fenestrated ASD closure, and ductus
      ligation. After an uneventful postoperative recovery, follow-up echocardiography
      at two months showed excellent results with tricuspid valve competency and normal
      biventricular function. Overall prognosis will probably depend on issues
      pertaining to tuberous sclerosis. 

PMID- 25870356
TI  - Left coronary artery stenosis causing left ventricular dysfunction in two
      children with supravalvular aortic stenosis.
AB  - Congenital supravalvar aortic stenosis (SVAS) is an arteriopathy associated with
      Williams-Beuren syndrome (WBS) and other isolated elastin gene deletions.
      Cardiovascular manifestations associated with WBS are characterized by
      obstructive arterial lesions such as SVAS and pulmonary artery stenosis in
      addition to bicuspid aortic valve and mitral valve prolapse. However, coronary
      artery ostial stenosis may be associated with SVAS, and it increases the risk of
      sudden death and may complicate surgical management. In this report, we present
      our experience with two patients having SVAS and left coronary artery ostial
      stenosis with associated left ventricular dysfunction. 

PMID- 25870357
TI  - Postpartum pulmonary embolism in a patient with Fontan circulation.
AB  - Pregnancy is typically not recommended in patients with Fontan circulation.
      Although patients are well aware of the risks for the mother and fetus, an
      increasing number opt to become pregnant. The higher rate of survival into
      adulthood post-Fontan procedure is a likely factor as a result of improved
      management of single ventricle anatomy. Postpartum thromboembolism is a known
      complication, but its prevalence and management are not clearly defined. We
      present a case of massive pulmonary embolism two weeks postpartum in a patient
      with double inlet left ventricle palliated with lateral tunnel Fontan. 

PMID- 25870358
TI  - Aorta-to-left atrial fistula developing after surgical removal of an atrial
      septal occlusion device eight years after original implantation.
AB  - Cardiac erosions may occur in a small percentage of patients after device closure
      of atrial septal defects. These devices have to be explanted. We report an aorta
      to-left atrial fistula after surgical explantation of the device eight years
      after implant for access to mitral valve repair. The importance of realizing the
      risk of subclinical cardiac erosion and subsequent fistula development after
      device removal is discussed. 

PMID- 25870359
TI  - Tetralogy of Fallot and anomalous origin of the left pulmonary artery from the
      ascending aorta associated with absent right internal carotid artery.
AB  - Anomalous origin of the left pulmonary artery from the ascending aorta is a rare
      cardiac malformation more commonly described with tetralogy of Fallot (TOF). The
      association of absent right carotid artery with TOF and anomalous left pulmonary
      artery from the ascending aorta has been rarely reported in the past. This case
      highlights the need for careful evaluation of the aortic arch and head vessels
      anatomy in patients with TOF because of the potential neurologic complications
      after surgery. 

PMID- 25870360
TI  - Oblique coronary artery prolongation approach in anomalous left coronary artery
      from the pulmonary artery in a low-birth-weight neonate.
AB  - A 19-day-old newborn girl weighing 1.9-kg was born with anomalous origin of the
      left coronary artery (LCA) from the pulmonary artery (PA). Because of the small
      anatomic structures and long distance between the anomalous origin of the LCA
      high within the left posterior sinus of the main PA, a simple transfer of the
      anomalous LCA to the aorta was deemed impossible. A coronary button was created
      with an oblique flap of tissue cut from the posterior pulmonary arterial wall. An
      oblique flap was created from the anterior aortic wall. The two flaps were used
      to create a tubular prolongation that connected the LCA to the aorta. This
      created a tension-free anastomosis with potential for growth. The aorta and PA
      were then patched with pericardium. A left coronary angiogram three years after
      surgery demonstrated a patent coronary tube. 

PMID- 25870361
TI  - Unique combination of atrioventricular septal defect with cor triatriatum and
      complete vascular ring.
AB  - Atrioventricular septal defect can present with one or more associated anomalies.
      Cor triatriatum (subdivided left atrium) and vascular rings are among the less
      frequent. We describe a two-month-old patient with these three cardiovascular
      anomalies. This case highlights the importance of exhaustive preoperative
      evaluation in order to achieve successful surgical correction in one stage. 

PMID- 25870362
TI  - Childhood presentation of interrupted aortic arch with persistent carotid ducts.
AB  - Interrupted aortic arch is a rare condition with typical presentation within the
      first few weeks of life, as the circulation is dependent upon patency of the
      arterial duct. Most cases are associated with intracardiac anomalies, the most
      common being a ventricular septal defect with some degree of hypoplasia and/or
      obstruction of the left ventricular outflow tract. Presentation beyond infancy is
      uncommon, and suggests the presence of well-developed collateral circulation.
      This case of childhood presentation of interrupted aortic arch and intact
      ventricular septum highlights the very unusual finding of bilateral collateral
      arteries consistent with persistent carotid ducts. Cardiac MRI angiography with
      three-dimensional reconstruction defined not only the site of interruption in the
      aortic arch but also the entire collateral circulation. 

PMID- 25870363
TI  - Use of HeartWare Ventricular Assist System for systemic ventricular support of a
      pediatric patient after Mustard procedure.
AB  - BACKGROUND: The HeartWare Ventricular Assist System is indicated to provide
      mechanical circulatory support of patients with intractable heart failure as a
      bridge to cardiac transplantation. We describe the use of this device to support
      the systemic right ventricle (RV) of a pediatric patient with New York Heart
      Association class IIIC congestive heart failure who had undergone Mustard
      procedure for D-transposition of the great vessels as an infant. CASE REPORT: A
      HeartWare ventricular assist device was implanted in the left chest of a 16-year
      old female patient (body surface area 1.43 m(2)) who presented with edema and
      later deteriorated, developing acute kidney injury, dysrhythmia, and pulmonary
      edema. RESULTS: The patient's edema and acute kidney injury resolved after device
      placement. She was discharged home and successfully underwent device removal with
      heart transplant five months later. CONCLUSION: The HeartWare device may be used
      for extended support as a systemic RV in a pediatric patient. It is feasible to
      consider using the device in this patient population.

PMID- 25870364
TI  - Mosaic 22q11.2 deletion and tetralogy of Fallot with absent pulmonary valve: an
      unreported association.
AB  - Chromosome 22q11.2 microdeletion is the most common microdeletion syndrome.
      Mosaic 22q11.2 deletions are very rare and only a few have been reported. We
      describe a case of a neonate with tetralogy of Fallot with absent pulmonary valve
      with mosaic 22q11.2 deletion. Fluorescent in situ hybridization analysis of
      lymphocytes showed a hemizygous 22q11.2 microdeletion in 66% of interphase
      nuclei. Microarray testing confirmed a 1.66 Mb deletion at 22q11.2. The child did
      not have any clinical manifestations of 22q11.2 deletion other than the cardiac
      malformation.

PMID- 25870365
TI  - Severe aortic regurgitation after device closure of patent ductus arteriosus: an
      unexpected killjoy.

PMID- 25870366
TI  - Jaroslav Stark, MD, FRCS, FACS, FACC--celebrating an icon of pediatric cardiac
      surgery at age 80 years.

PMID- 25870367
TI  - The hole between the ventricles in the setting of common arterial trunk.

PMID- 25870368
TI  - Muscular ventricular septal defect in a newborn with truncus arteriosous
      communis: perventricular transcatheter closure under echocardiographic guidance
      only: a case report--response to the comment of Dr Anderson.

PMID- 25870370
TI  - Emergency management of heat exchanger leak on cardiopulmonary bypass with
      hypothermia.
AB  - Heat exchanger leak on cardiopulmonary bypass is very rare, but serious. The
      exact incidence is not known. It is an emergency associated with the potential
      risk of blood contamination, air embolism and haemolysis, difficulty with re
      warming, acidosis, subsequent septic shock, multi-organ failure and death. We
      present a prompt, highly co-ordinated algorithm for the successful management of
      this important rare complication. There is need for further research to look for
      safety devices that detect leaks and techniques to reduce bacterial load. It is
      essential that teams practice oxygenator change-out routines and have a well
      established change-out protocol. 

PMID- 25870369
TI  - Blood pressure and adverse events during continuous flow left ventricular assist
      device support.
AB  - BACKGROUND: Adverse events (AEs), such as intracranial hemorrhage, thromboembolic
      event, and progressive aortic insufficiency, create substantial morbidity and
      mortality during continuous flow left ventricular assist device support yet their
      relation to blood pressure control is underexplored. METHODS AND RESULTS: A
      multicenter retrospective review of patients supported for at least 30 days and
      <=18 months by a continuous flow left ventricular assist device from June 2006 to
      December 2013 was conducted. All outpatient Doppler blood pressure (DOPBP)
      recordings were averaged up to the time of intracranial hemorrhage,
      thromboembolic event, or progressive aortic insufficiency. DOPBP was analyzed as
      a categorical variable grouped as high (>90 mm Hg; n=40), intermediate (80-90 mm
      Hg; n=52), and controlled (<80 mm Hg; n=31). Cumulative survival free from an AE
      was calculated using Kaplan-Meier curves and Cox hazard ratios were derived.
      Patients in the high DOPBP group had worse baseline renal function, lower
      angiotensin-converting enzyme inhibitor or angiotensin receptor blocker usage
      during continuous flow left ventricular assist device support, and a more
      prevalent history of hypertension. Twelve (30%) patients in the high DOPBP group
      had an AE, in comparison with 7 (13%) patients in the intermediate DOPBP group
      and only 1 (3%) in the controlled DOPBP group. The likelihood of an AE increased
      in patients with a high DOPBP (adjusted hazard ratios [95% confidence interval],
      16.4 [1.8-147.3]; P=0.012 versus controlled and 2.6 [0.93-7.4]; P=0.068 versus
      intermediate). Overall, a similar association was noted for the risk of
      intracranial hemorrhage (P=0.015) and progressive aortic insufficiency (P=0.078)
      but not for thromboembolic event (P=0.638). Patients with an AE had a higher
      DOPBP (90+/-10 mm Hg) in comparison with those without an AE (85+/-10 mm Hg;
      P=0.05). CONCLUSIONS: In a population at risk, higher DOPBP during continuous
      flow left ventricular assist device support was significantly associated with a
      composite of AEs.

PMID- 25870371
TI  - Adding insult to injury: partner depression moderates the association between
      partner-regulation attempts and partners' motivation to resolve interpersonal
      problems.
AB  - Intimates regularly confront their partners to motivate them to change
      undesirable behaviors. Nevertheless, contextual perspectives suggest that
      qualities of the partner may determine the implications of such attempts.
      Consistent with these ideas, a pilot study of romantic relationships, an
      observational study of newlyweds, and a diary study of married couples
      demonstrated that partner depression moderates the association between
      confrontational partner-regulation behaviors and partners' motivation, such that
      confrontational behaviors were associated with marginally greater motivation to
      resolve problems among partners who were experiencing relatively few depressive
      symptoms, but significantly less motivation among partners who were experiencing
      relatively more depressive symptoms. Furthermore, Study 2 provided evidence for
      the mechanism of these effects--relationship self-efficacy. Finally, these
      studies also demonstrated that benevolent behaviors were particularly motivating
      for partners who were experiencing more depressive symptoms. These findings
      highlight the important roles played by depression, relationship self-efficacy,
      and context in interpersonal communication.

PMID- 25870372
TI  - Turf war over diagnostic testing.

PMID- 25870373
TI  - Breast cancer risk reduction therapy: the low-hanging fruit.

PMID- 25870374
TI  - NCCN: Touched by Cancer.

PMID- 25870375
TI  - A novel approach using sorafenib in alpha fetoprotein-producing hepatoid
      adenocarcinoma of the lung.
AB  - Hepatoid adenocarcinoma of the lung (HAL) is an extremely rare cancer without
      clear treatment guidance and with a poor prognosis. This report discusses a 64
      year-old man who presented with complaints of hemoptysis and was found to have a
      right upper lobe (RUL) lung mass on chest CT with presence of a right hilar mass
      and retrocaval lymphadenopathy, and metastasis to the vertebral spine and rib.
      The patient was diagnosed with T2N2M1 (stage IV) unresectable disease. A biopsy
      of the RUL mass revealed hepatoid variant adenocarcinoma. Immunohistochemical
      stains showed tumor cells positive for CK7, AFP, Hep Par 1, napsin A, and
      cytoplasmic TTF-1 staining. In contrast, CK5, CK6, and CK20 were negative, and
      EGFR was wild-type. Serum alpha fetoprotein (AFP) level was elevated at 181
      ng/mL. The patient was treated with platinum-based doublet chemotherapy and
      sorafenib, and his AFP level decreased to 25 ng/mL. This case report presents the
      novel use of sorafenib in combination with platinum-based doublet chemotherapy in
      EGFR wild-type HAL, which led to a partial response. Single-agent sorafenib led
      to stable disease overall, achieving a survival among the longest reported for
      unresectable stage IV, all while maintaining an ECOG performance status of 0 to
      1.

PMID- 25870376
TI  - Cervical Cancer, Version 2.2015.
AB  - The NCCN Guidelines for Cervical Cancer provide interdisciplinary recommendations
      for treating cervical cancer. These NCCN Guidelines Insights summarize the NCCN
      Cervical Cancer Panel's discussion and major guideline updates from 2014 and
      2015. The recommended systemic therapy options for recurrent and metastatic
      cervical cancer were amended upon panel review of new survival data and the FDA's
      approval of bevacizumab for treating late-stage cervical cancer. This article
      outlines relevant data and provides insight into panel decisions regarding
      various combination regimens. Additionally, a new section was added to provide
      additional guidance on key principles of evaluation and surgical staging in
      cervical cancer. This article highlights 2 areas of active investigation and
      debate from this new section: sentinel lymph node mapping and fertility-sparing
      treatment approaches.

PMID- 25870377
TI  - Impact of NCI-mandated scientific review on protocol development and content.
AB  - PURPOSE: The NCI requirement that clinical trials at NCI-designated cancer
      centers undergo scientific review in addition to Institutional Review Board
      review is unique among medical specialties. We evaluated the impact of this
      process on protocol development and content. METHODS: We analyzed cancer clinical
      trials that underwent full board review by the Harold C. Simmons Cancer Center
      Protocol Review and Monitoring Committee (PRMC) from January 1, 2009, through
      June 30, 2013. We analyzed associations between trial characteristics, PRMC
      decisions, and protocol modifications using Chi-square testing, Fishers exact
      testing, and logistic regression. RESULTS: A total of 226 trials were analyzed.
      Of these, 77% were industry-sponsored and 23% were investigator-initiated.
      Initial PRMC decisions were: approval (40%), provisional approval (52%), deferral
      (7%), and disapproval (1%). These decisions were associated with study sponsor
      (P<.001) and phase (P<.001). Ultimately, 97% of industry-sponsored and 90% of
      investigator-initiated trials were approved (P=.05). Changes were requested for
      27% of industry-sponsored trials compared with 54% of investigator-initiated
      trials (P<.001). Total changes requested (mean, 5.6 vs 2.4; P<.001) and
      implemented (mean, 4.6 vs 2.1; P=.008) per protocol were significantly greater
      for investigator-initiated trials. Changes related to study design were more
      commonly requested (35% vs 13% of trials) and implemented (40% vs 5% of trials)
      for investigator-initiated trials compared with industry-sponsored trials
      (P=.03). CONCLUSIONS: NCI-mandated scientific protocol review seems to have a
      substantial impact on investigator-initiated trials but less effect on industry
      sponsored trials. These findings may provide guidance on development and
      prioritization of institutional protocol review policies.

PMID- 25870378
TI  - Delayed recovery and increased severity of Paclitaxel-induced peripheral
      neuropathy in patients with diabetes.
AB  - PURPOSE: Although diabetes mellitus (DM) is recognized as a risk factor for
      chemotherapy-induced neurotoxicity, its true impact on intensity and time course
      of peripheral neuropathy is still unclear. The goal was to analyze the relevance
      of preexisting DM to weekly paclitaxel-induced peripheral neuropathy (PIPN).
      METHODS: We performed a retrospective case-control study (1:2) including a total
      of 129 patients with breast cancer (43 with DM and 86 controls) treated with
      single-agent weekly paclitaxel (wP). RESULTS: Compared with controls, patients
      with DM treated with wP experienced PIPN more frequently (74.4% vs 58.4%; P=.016)
      and with higher severity (grade 2-3: 51.2% vs 27.7%; P=.014). A significant delay
      in PIPN resolution was observed in women with DM (P=.001) and, in a multivariate
      analysis, DM was the only independent predictor for delayed recovery (hazard
      ratio [HR], 0.16; 95% CI, 0.05-0.55; P=.003). After 2 years, 68.7% of patients
      with DM (vs 29.2% of women without DM) still experienced PIPN, which was
      functionally significant (grade 2-3) in 18.2%. CONCLUSIONS: Significantly more
      dose delays and reductions because of PIPN occurred in patients with DM.
      Preexisting DM associates with long-lasting significant PIPN in patients treated
      with wP. Benefits and risks of long-term significant PIPN should be carefully
      balanced in patients with DM before starting wP chemotherapy.

PMID- 25870380
TI  - Development of a hematology/oncology ICD-10 documentation job aid.
AB  - Conversion to the International Classification of Diseases, 10th Revision,
      Clinical Modification (ICD-10-CM) was mandated for October 1, 2014, but was
      delayed by one year. ICD-10 accommodates newly developed diagnoses and procedures
      and is expected to help measure quality of care. When implemented, it will impact
      oncology practices because of conversion costs, loss of productivity, and billing
      problems. Clinical documentation must meet the specificity required by ICD-10
      codes or risk denial of payments, which are projected to dramatically increase.
      In preparation for the now delayed conversion, the ICD-10 transition team at the
      Seattle Cancer Care Alliance (SCCA) examined the ICD-10 codes for primary
      hematology/oncology diagnoses and comorbidities of cancer and therapy seen at our
      institution to identify the need for and feasibility of developing a printable
      job aid to guide clinical documentation. We found that the variable complexity of
      ICD-10 codes in hematology/oncology frequently requires nonintuitive specificity
      likely to be overlooked without prompting. We were able to develop a succinct and
      facile documentation aid usable in both electronic and printed forms that
      includes all hematology/oncology diagnoses and the comorbidities most frequently
      seen in our multidisciplinary institution. This document is organized in a
      notebook format for easy review and will be continuously improved with feedback
      from practitioners. It is available for free download from the SCCA Web site.

PMID- 25870379
TI  - Historical views, conventional approaches, and evolving management strategies for
      myeloproliferative neoplasms.
AB  - The classical Philadelphia chromosome-negative myeloproliferative neoplasms
      (MPN), which include essential thrombocythemia, polycythemia vera, and
      myelofibrosis (MF), are in a new era of molecular diagnosis, ushered in by the
      identification of the JAK2(V617F) and cMPL mutations in 2005 and 2006,
      respectively, and the CALR mutations in 2013. Coupled with increased knowledge of
      disease pathogenesis and refined diagnostic criteria and prognostic scoring
      systems, a more nuanced appreciation has emerged of the burden of MPN in the
      United States, including the prevalence, symptom burden, and impact on quality of
      life. Biological advances in MPN have translated into the rapid development of
      novel therapeutics, culminating in the approval of the first treatment for MF,
      the JAK1/JAK2 inhibitor ruxolitinib. However, certain practical aspects of care,
      such as those regarding diagnosis, prevention of vascular events, choice of
      cytoreductive agent, and planning for therapies, present challenges for
      hematologists/oncologists, and are discussed in this article.

PMID- 25870381
TI  - Breast Cancer Version 2.2015.
AB  - Breast cancer is the most common malignancy in women in the United States and is
      second only to lung cancer as a cause of cancer death. The overall management of
      breast cancer includes the treatment of local disease with surgery, radiation
      therapy, or both, and the treatment of systemic disease with cytotoxic
      chemotherapy, endocrine therapy, biologic therapy, or combinations of these. This
      portion of the NCCN Guidelines discusses recommendations specific to the
      locoregional management of clinical stage I, II, and IIIA (T3N1M0) tumors. 

PMID- 25870382
TI  - Routine use of zoledronic acid in early-stage breast cancer.
AB  - Zoledronic acid, a potent nitrogen-containing bisphosphonate, plays a key role in
      preventing complications of bone metastases in metastatic breast cancer, but its
      affect on early-stage breast cancer has been unclear. The preclinical data
      supporting the anticancer effects of zoledronic acid are compelling and several
      recent clinical trials have suggested that it reduces breast cancer recurrence in
      certain patient subgroups. Given these anticancer effects and reasonable safety
      profile, this therapeutic option could be discussed with patients. This article
      focuses on the results of supporting preclinical and clinical data evaluating the
      role of zoledronic acid in adjuvant breast cancer therapy. 

PMID- 25870383
TI  - Surgical management of de novo stage IV breast cancer.
AB  - Management of the intact primary tumor in women presenting with stage IV breast
      cancer has classically been determined by the presence or absence of symptoms.
      However, multiple retrospective reviews completed over the past decade suggest a
      survival advantage with resection of the intact, asymptomatic primary tumor in
      these women. These reviews are not without bias, and recently completed
      randomized trials do not support a significant survival benefit, although local
      control benefits may exist. Completion of ongoing trials is needed to reach a
      definitive conclusion regarding the merit of primary tumor resection for local
      control and survival. Until unbiased data are available, local therapy for the
      asymptomatic primary cannot be routinely recommended, but may be considered in
      selected individuals, with multidisciplinary input, when systemic disease is well
      controlled.

PMID- 25870384
TI  - Delivering on the promise of patient-centered care.

PMID- 25870386
TI  - The Process Model of Group-Based Emotion: Integrating Intergroup Emotion and
      Emotion Regulation Perspectives.
AB  - Scholars interested in emotion regulation have documented the different goals and
      strategies individuals have for regulating their emotions. However, little
      attention has been paid to the regulation of group-based emotions, which are
      based on individuals' self-categorization as a group member and occur in response
      to situations perceived as relevant for that group. We propose a model for
      examining group-based emotion regulation that integrates intergroup emotions
      theory and the process model of emotion regulation. This synergy expands
      intergroup emotion theory by facilitating further investigation of different
      goals (i.e., hedonic or instrumental) and strategies (e.g., situation selection
      and modification strategies) used to regulate group-based emotions. It also
      expands emotion regulation research by emphasizing the role of self
      categorization (e.g., as an individual or a group member) in the emotional
      process. Finally, we discuss the promise of this theoretical synergy and suggest
      several directions for future research on group-based emotion regulation.

PMID- 25870387
TI  - Re: Survival outcomes after contralateral prophylactic mastectomy: a decision
      analysis.

PMID- 25870388
TI  - Response.

PMID- 25870389
TI  - Social immunity and the evolution of group living in insects.
AB  - The evolution of group living requires that individuals limit the inherent risks
      of parasite infection. To this end, group living insects have developed a unique
      capability of mounting collective anti-parasite defences, such as allogrooming
      and corpse removal from the nest. Over the last 20 years, this phenomenon (called
      social immunity) was mostly studied in eusocial insects, with results emphasizing
      its importance in derived social systems. However, the role of social immunity in
      the early evolution of group living remains unclear. Here, I investigate this
      topic by first presenting the definitions of social immunity and discussing their
      applications across social systems. I then provide an up-to-date appraisal of the
      collective and individual mechanisms of social immunity described in eusocial
      insects and show that they have counterparts in non-eusocial species and even
      solitary species. Finally, I review evidence demonstrating that the increased
      risks of parasite infection in group living species may both decrease and
      increase the level of personal immunity, and discuss how the expression of social
      immunity could drive these opposite effects. By highlighting similarities and
      differences of social immunity across social systems, this review emphasizes the
      potential importance of this phenomenon in the early evolution of the multiple
      forms of group living in insects. 

PMID- 25870390
TI  - Sex, social status and physiological stress in primates: the importance of social
      and glucocorticoid dynamics.
AB  - Social status has been associated with health consequences, although the
      mechanisms by which status affects health are relatively unknown. At the
      physiological level, many studies have investigated the potential relationship
      between social behaviour/rank and physiological stress, with a particular focus
      on glucocorticoid (GC) production. GCs are of interest because of their
      experimentally established influence on health-related processes such as
      metabolism and immune function. Studies in a variety of species, in both
      naturalistic and laboratory settings, have led to complex outcomes. This paper
      reviews findings from primates and rodents and proposes a psychologically and
      physiologically relevant framework in which to study the relationship between
      social status and GC function. We (i) compare status-specific GC production
      between male and female primates, (ii) review the functional significance of
      different temporal patterns of GC production, (iii) propose ways to assess these
      temporal dynamics, and (iv) present novel hypotheses about the relationship
      between social status and GC temporal dynamics, and potential fitness and health
      implications. To understand whether GC production mediates social status-related
      fitness disparities, we must consider social contest conditions and the temporal
      dynamics of GC production. This framework will provide greater insights into the
      relationship between social status, physiological stress and health. 

PMID- 25870391
TI  - Social instability and immunity in rhesus monkeys: the role of the sympathetic
      nervous system.
AB  - Social instability can adversely affect endocrine, immune and health outcomes,
      and recent evidence suggests that the sympathetic nervous system (SNS) might
      mediate these effects. We conducted two studies with adult male rhesus monkeys
      (Macaca mulatta) to understand how social conditions affect measures of SNS
      activity and immune function. In Experiment 1, animals were socialized in stable
      social conditions, then were switched to unstable (stressful) social conditions,
      then were returned to stable conditions. Analysis revealed quadratic effects for
      measures of behaviour, urinary metabolites of epinephrine and norepinephrine, and
      expression of immune response genes: as expected, social instability adversely
      impacted most measures, and the effects remediated upon re-imposition of stable
      conditions. Cortisol levels were unaffected. In Experiment 2, we used the
      sympathomimetic drug methamphetamine to challenge the SNS; animals also underwent
      socialization in stable or unstable groups. Surprisingly, while methamphetamine
      elevated plasma catecholamines, responses in lymph nodes tracked the social, and
      not the drug, condition: social instability upregulated the density of SNS fibres
      in lymph nodes and downregulated Type I interferon gene expression. Together,
      these results indicate that the SNS is extremely sensitive to social conditions;
      full understanding of the adverse effects of social instability on health should
      therefore incorporate measures of this health-relevant system. 

PMID- 25870392
TI  - Implications of the behavioural immune system for social behaviour and human
      health in the modern world.
AB  - The 'behavioural immune system' is composed of mechanisms that evolved as a means
      of facilitating behaviours that minimized infection risk and enhanced fitness.
      Recent empirical research on human populations suggests that these mechanisms
      have unique consequences for many aspects of human sociality--including sexual
      attitudes, gregariousness, xenophobia, conformity to majority opinion and
      conservative sociopolitical attitudes. Throughout much of human evolutionary
      history, these consequences may have had beneficial health implications; but
      health implications in modern human societies remain unclear. This article
      summarizes pertinent ways in which modern human societies are similar to and
      different from the ecologies within which the behavioural immune system evolved.
      By attending to these similarities and differences, we identify a set of
      plausible implications-both positive and negative-that the behavioural immune
      system may have on health outcomes in contemporary human contexts. We discuss
      both individual-level infection risk and population-level epidemiological
      outcomes. We also discuss a variety of additional implications, including
      compliance with public health policies, the adoption of novel therapeutic
      interventions and actual immunological functioning. Research on the behavioural
      immune system, and its implications in contemporary human societies, can provide
      unique insights into relationships between fitness, sociality and health.

PMID- 25870394
TI  - Opposing effects of allogrooming on disease transmission in ant societies.
AB  - To prevent epidemics, insect societies have evolved collective disease defences
      that are highly effective at curing exposed individuals and limiting disease
      transmission to healthy group members. Grooming is an important sanitary
      behaviour--either performed towards oneself (self-grooming) or towards others
      (allogrooming)--to remove infectious agents from the body surface of exposed
      individuals, but at the risk of disease contraction by the groomer. We use garden
      ants (Lasius neglectus) and the fungal pathogen Metarhizium as a model system to
      study how pathogen presence affects self-grooming and allogrooming between
      exposed and healthy individuals. We develop an epidemiological SIS model to
      explore how experimentally observed grooming patterns affect disease spread
      within the colony, thereby providing a direct link between the expression and
      direction of sanitary behaviours, and their effects on colony-level epidemiology.
      We find that fungus-exposed ants increase self-grooming, while simultaneously
      decreasing allogrooming. This behavioural modulation seems universally adaptive
      and is predicted to contain disease spread in a great variety of host-pathogen
      systems. In contrast, allogrooming directed towards pathogen-exposed individuals
      might both increase and decrease disease risk. Our model reveals that the effect
      of allogrooming depends on the balance between pathogen infectiousness and
      efficiency of social host defences, which are likely to vary across host-pathogen
      systems.

PMID- 25870393
TI  - Infectious disease transmission and contact networks in wildlife and livestock.
AB  - The use of social and contact networks to answer basic and applied questions
      about infectious disease transmission in wildlife and livestock is receiving
      increased attention. Through social network analysis, we understand that wild
      animal and livestock populations, including farmed fish and poultry, often have a
      heterogeneous contact structure owing to social structure or trade networks.
      Network modelling is a flexible tool used to capture the heterogeneous contacts
      of a population in order to test hypotheses about the mechanisms of disease
      transmission, simulate and predict disease spread, and test disease control
      strategies. This review highlights how to use animal contact data, including
      social networks, for network modelling, and emphasizes that researchers should
      have a pathogen of interest in mind before collecting or using contact data. This
      paper describes the rising popularity of network approaches for understanding
      transmission dynamics in wild animal and livestock populations; discusses the
      common mismatch between contact networks as measured in animal behaviour and
      relevant parasites to match those networks; and highlights knowledge gaps in how
      to collect and analyse contact data. Opportunities for the future include
      increased attention to experiments, pathogen genetic markers and novel
      computational tools. 

PMID- 25870395
TI  - Social status, immune response and parasitism in males: a meta-analysis.
AB  - In male vertebrates, two conflicting paradigms--the energetic costs of high
      dominance rank and the chronic stress of low rank--have been proposed to explain
      patterns of immune function and parasitism. To date, neither paradigm has
      provided a complete explanation for status-related differences in male health.
      Here, we applied meta-analyses to test for correlations between male social
      status, immune responses and parasitism. We used an ecoimmunological framework,
      which proposes that males should re-allocate investment in different immune
      components depending on the costs of dominance or subordination. Spanning 297
      analyses, from 77 studies on several vertebrate taxa, we found that most immune
      responses were similar between subordinate and dominant males, and neither
      dominant nor subordinate males consistently invested in predictable immune
      components. However, subordinate males displayed significantly lower delayed-type
      hypersensitivity and higher levels of some inflammatory cytokines than dominant
      males, while dominant males exhibited relatively lower immunoglobulin responses
      than subordinate males. Despite few differences in immunity, dominant males
      exhibited consistently higher parasitism than subordinate males, including
      protozoan blood parasites, ectoparasites and gastrointestinal helminths. We
      discuss our results in the context of the costs of dominance and subordination
      and advocate future work that measures both parasitism and immune responses in
      wild systems.

PMID- 25870396
TI  - Brown spider monkeys (Ateles hybridus): a model for differentiating the role of
      social networks and physical contact on parasite transmission dynamics.
AB  - Elevated risk of disease transmission is considered a major cost of sociality,
      although empirical evidence supporting this idea remains scant. Variation in
      spatial cohesion and the occurrence of social interactions may have profound
      implications for patterns of interindividual parasite transmission. We used a
      social network approach to shed light on the importance of different aspects of
      group-living (i.e. within-group associations versus physical contact) on patterns
      of parasitism in a neotropical primate, the brown spider monkey (Ateles
      hybridus), which exhibits a high degree of fission-fusion subgrouping. We used
      daily subgroup composition records to create a 'proximity' network, and built a
      separate 'contact' network using social interactions involving physical contact.
      In the proximity network, connectivity between individuals was homogeneous,
      whereas the contact network highlighted high between-individual variation in the
      extent to which animals had physical contact with others, which correlated with
      an individual's age and sex. The gastrointestinal parasite species richness of
      highly connected individuals was greater than that of less connected individuals
      in the contact network, but not in the proximity network. Our findings suggest
      that among brown spider monkeys, physical contact impacts the spread of several
      common parasites and supports the idea that pathogen transmission is one cost
      associated with social contact. 

PMID- 25870397
TI  - Infectious disease and group size: more than just a numbers game.
AB  - Increased risk of infectious disease is assumed to be a major cost of group
      living, yet empirical evidence for this effect is mixed. We studied whether
      larger social groups are more subdivided structurally. If so, the social
      subdivisions that form in larger groups may act as barriers to the spread of
      infection, weakening the association between group size and infectious disease.
      To investigate this 'social bottleneck' hypothesis, we examined the association
      between group size and four network structure metrics in 43 vertebrate and
      invertebrate species. We focused on metrics involving modularity, clustering,
      distance and centralization. In a meta-analysis of intraspecific variation in
      social networks, modularity showed positive associations with network size, with
      a weaker but still positive effect in cross-species analyses. Network distance
      also showed a positive association with group size when using intraspecific
      variation. We then used a theoretical model to explore the effects of subgrouping
      relative to other effects that influence disease spread in socially structured
      populations. Outbreaks reached higher prevalence when groups were larger, but
      subgrouping reduced prevalence. Subgrouping also acted as a 'brake' on disease
      spread between groups. We suggest research directions to understand the
      conditions under which larger groups become more subdivided, and to devise new
      metrics that account for subgrouping when investigating the links between
      sociality and infectious disease risk. 

PMID- 25870398
TI  - Competing pressures on populations: long-term dynamics of food availability, food
      quality, disease, stress and animal abundance.
AB  - Despite strong links between sociality and fitness that ultimately affect the
      size of animal populations, the particular social and ecological factors that
      lead to endangerment are not well understood. Here, we synthesize approximately
      25 years of data and present new analyses that highlight dynamics in forest
      composition, food availability, the nutritional quality of food, disease,
      physiological stress and population size of endangered folivorous red colobus
      monkeys (Procolobus rufomitratus). There is a decline in the quality of leaves 15
      and 30 years following two previous studies in an undisturbed area of forest. The
      consumption of a low-quality diet in one month was associated with higher
      glucocorticoid levels in the subsequent month and stress levels in groups living
      in degraded forest fragments where diet was poor was more than twice those in
      forest groups. In contrast, forest composition has changed and when red colobus
      food availability was weighted by the protein-to-fibre ratio, which we have shown
      positively predicts folivore biomass, there was an increase in the availability
      of high-quality trees. Despite these changing social and ecological factors, the
      abundance of red colobus has remained stable, possibly through a combination of
      increasing group size and behavioural flexibility. 

PMID- 25870399
TI  - Ectoparasites and fitness of female Columbian ground squirrels.
AB  - Parasites play an important role in the evolution of host traits via natural
      selection, coevolution and sexually selected ornaments used in mate choice. These
      evolutionary scenarios assume fitness costs for hosts. To test this assumption,
      we conducted an ectoparasite removal experiment in free-living Columbian ground
      squirrels (Urocittelus columbianus) in four populations over three years. Adult
      females were randomly chosen to be either experimentally treated with anti
      parasite treatments (spot-on solution and flea powder, N = 61) or a sham
      treatment (control, N = 44). We expected that experimental females would show
      better body condition, increased reproductive success and enhanced survival.
      Contrary to our expectations, body mass was not significantly different between
      treatments at mating, birth of litter or weaning of young. Further, neither
      number nor size of young at weaning differed significantly between the two
      treatments. Survival to the next spring for adult females and juveniles was not
      significantly different between experimental and control treatments. Finally,
      annual fitness was not affected by the treatments. We concluded that females and
      their offspring were able compensate for the presence of ectoparasites,
      suggesting little or no fitness costs of parasites for females in the different
      colonies and during the years of our experiments. 

PMID- 25870400
TI  - Perceived social isolation, evolutionary fitness and health outcomes: a lifespan
      approach.
AB  - Sociality permeates each of the fundamental motives of human existence and plays
      a critical role in evolutionary fitness across the lifespan. Evidence for this
      thesis draws from research linking deficits in social relationship--as indexed by
      perceived social isolation (i.e. loneliness)--with adverse health and fitness
      consequences at each developmental stage of life. Outcomes include depression,
      poor sleep quality, impaired executive function, accelerated cognitive decline,
      unfavourable cardiovascular function, impaired immunity, altered hypothalamic
      pituitary-adrenocortical activity, a pro-inflammatory gene expression profile and
      earlier mortality. Gaps in this research are summarized with suggestions for
      future research. In addition, we argue that a better understanding of naturally
      occurring variation in loneliness, and its physiological and psychological
      underpinnings, in non-human species may be a valuable direction to better
      understand the persistence of a 'lonely' phenotype in social species, and its
      consequences for health and fitness.

PMID- 25870401
TI  - The sociality-health-fitness nexus: synthesis, conclusions and future directions.
AB  - This theme issue has highlighted the links between sociality, health and fitness
      in a broad range of organisms, and with approaches that include field and captive
      studies of animals, comparative and meta-analyses, theoretical modelling and
      clinical and psychological studies of humans. In this concluding chapter, we
      synthesize the results of these diverse studies into some of the key concepts
      discussed in this issue, focusing on risks of infectious disease through social
      contact, the effects of competition in groups on susceptibility to disease, and
      the integration of sociality into research on life-history trade-offs.
      Interestingly, the studies in this issue both support pre-existing hypotheses,
      and in other ways challenge those hypotheses. We focus on unexpected results,
      including a lack of association between ectoparasites and fitness and weak
      results from a meta-analysis of the links between dominance rank and immune
      function, and place these results in a broader context. We also review relevant
      topics that were not covered fully in this theme issue, including self-medication
      and sickness behaviours, society-level defences against infectious disease,
      sexual selection, evolutionary medicine, implications for conservation biology
      and selective pressures on parasite traits. We conclude by identifying general
      open questions to stimulate and guide future research on the links between
      sociality, health and fitness. 

PMID- 25870403
TI  - Correction to 'Physical behaviour of anthropogenic light propagation into the
      nocturnal environment'.

PMID- 25870402
TI  - Sociality and health: impacts of sociality on disease susceptibility and
      transmission in animal and human societies.
AB  - This paper introduces a theme issue presenting the latest developments in
      research on the impacts of sociality on health and fitness. The articles that
      follow cover research on societies ranging from insects to humans. Variation in
      measures of fitness (i.e. survival and reproduction) has been linked to various
      aspects of sociality in humans and animals alike, and variability in individual
      health and condition has been recognized as a key mediator of these
      relationships. Viewed from a broad evolutionary perspective, the evolutionary
      transitions from a solitary lifestyle to group living have resulted in several
      new health-related costs and benefits of sociality. Social transmission of
      parasites within groups represents a major cost of group living, but some
      behavioural mechanisms, such as grooming, have evolved repeatedly to reduce this
      cost. Group living also has created novel costs in terms of altered
      susceptibility to infectious and non-infectious disease as a result of the
      unavoidable physiological consequences of social competition and integration,
      which are partly alleviated by social buffering in some vertebrates. Here, we
      define the relevant aspects of sociality, summarize their health-related costs
      and benefits, and discuss possible fitness measures in different study systems.
      Given the pervasive effects of social factors on health and fitness, we propose a
      synthesis of existing conceptual approaches in disease ecology, ecological
      immunology and behavioural neurosciences by adding sociality as a key factor,
      with the goal to generate a broader framework for organismal integration of
      health-related research. 

PMID- 25870404
TI  - Childhood self-control and unemployment throughout the life span: evidence from
      two British cohort studies.
AB  - The capacity for self-control may underlie successful labor-force entry and job
      retention, particularly in times of economic uncertainty. Analyzing unemployment
      data from two nationally representative British cohorts (N = 16,780), we found
      that low self-control in childhood was associated with the emergence and
      persistence of unemployment across four decades. On average, a 1-SD increase in
      self-control was associated with a reduction in the probability of unemployment
      of 1.4 percentage points after adjustment for intelligence, social class, and
      gender. From labor-market entry to middle age, individuals with low self-control
      experienced 1.6 times as many months of unemployment as those with high self
      control. Analysis of monthly unemployment data before and during the 1980s
      recession showed that individuals with low self-control experienced the greatest
      increases in unemployment during the recession. Our results underscore the
      critical role of self-control in shaping life-span trajectories of occupational
      success and in affecting how macroeconomic conditions affect unemployment levels
      in the population. 

PMID- 25870405
TI  - Not so innocent: toddlers' inferences about costs and culpability.
AB  - Adults' social evaluations are influenced by their perception of other people's
      competence and motivation: Helping when it is difficult to help is praiseworthy,
      and not helping when it is easy to help is reprehensible. Here, we look at
      whether children's social evaluations are affected by the costs that agents
      incur. We found that toddlers can use the time and effort associated with goal
      directed actions to distinguish agents, and that children prefer agents who incur
      fewer costs in completing a goal. When two agents refuse to help, children retain
      a preference for the more competent agent but infer that the less competent agent
      is nicer. These results suggest that children value agents who incur fewer costs,
      but understand that failure to engage in a low-cost action implies a lack of
      motivation. We propose that a naive utility calculus underlies inferences from
      the costs and rewards of goal-directed action and thereby supports social
      cognition. 

PMID- 25870406
TI  - A sniff of happiness.
AB  - It is well known that feelings of happiness transfer between individuals through
      mimicry induced by vision and hearing. The evidence is inconclusive, however, as
      to whether happiness can be communicated through the sense of smell via
      chemosignals. As chemosignals are a known medium for transferring negative
      emotions from a sender to a receiver, we examined whether chemosignals are also
      involved in the transmission of positive emotions. Positive emotions are
      important for overall well-being and yet relatively neglected in research on
      chemosignaling, arguably because of the stronger survival benefits linked with
      negative emotions. We observed that exposure to body odor collected from senders
      of chemosignals in a happy state induced a facial expression and perceptual
      processing style indicative of happiness in the receivers of those signals. Our
      findings suggest that not only negative affect but also a positive state
      (happiness) can be transferred by means of odors. 

PMID- 25870407
TI  - Live cell imaging of duplex siRNA intracellular trafficking.
AB  - Intracellular distribution of siRNA after in vitro transfection typically depends
      on lipopolyplexes, which must release the siRNA into the cytosol. Here, the fate
      of siRNAs was monitored by FRET-based live cell imaging. Subsequent to in situ
      observation of uptake and release processes, this approach allowed the
      observation of a number of hitherto uncharacterized intracellular distribution
      and degradation processes, commencing with a burst of endosomal releases,
      followed, in some cases, by fast siRNA influx into the nucleus. The continued
      observation of intact siRNA against a background of free fluorophores resulting
      from advanced degradation was possible by a specifically developed imaging
      algorithm, which identified populations of intact siRNA in pixels based on FRET.
      This proved to be essential in the end point definition of siRNA distribution,
      which typically featured partially degraded siRNA pools in perinuclear
      structures. Our results depict the initial 4 h as a critical time window,
      characterized by fast initial burst release into the cytosol, which lay the
      foundations for subsequent intracellular distribution of siRNA. Combination with
      a subsequent slower, but sustained release from endosomal reservoirs may
      contribute to the efficiency and duration of RNAi, and explain the success of
      lipopolyplexes in RNAi experiments in cell culture. 

PMID- 25870408
TI  - Identification of protein coding regions in RNA transcripts.
AB  - Massive parallel sequencing of RNA transcripts by next-generation technology (RNA
      Seq) generates critically important data for eukaryotic gene discovery. Gene
      finding in transcripts can be done by statistical (alignment-free) as well as by
      alignment-based methods. We describe a new tool, GeneMarkS-T, for ab initio
      identification of protein-coding regions in RNA transcripts. The algorithm
      parameters are estimated by unsupervised training which makes unnecessary
      manually curated preparation of training sets. We demonstrate that (i) the
      unsupervised training is robust with respect to the presence of transcripts
      assembly errors and (ii) the accuracy of GeneMarkS-T in identifying protein
      coding regions and, particularly, in predicting translation initiation sites in
      modelled as well as in assembled transcripts compares favourably to other
      existing methods. 

PMID- 25870409
TI  - Large scale analysis of the mutational landscape in HT-SELEX improves aptamer
      discovery.
AB  - High-Throughput (HT) SELEX combines SELEX (Systematic Evolution of Ligands by
      EXponential Enrichment), a method for aptamer discovery, with massively parallel
      sequencing technologies. This emerging technology provides data for a global
      analysis of the selection process and for simultaneous discovery of a large
      number of candidates but currently lacks dedicated computational approaches for
      their analysis. To close this gap, we developed novel in-silico methods to
      analyze HT-SELEX data and utilized them to study the emergence of polymerase
      errors during HT-SELEX. Rather than considering these errors as a nuisance, we
      demonstrated their utility for guiding aptamer discovery. Our approach builds on
      two main advancements in aptamer analysis: AptaMut-a novel technique allowing for
      the identification of polymerase errors conferring an improved binding affinity
      relative to the 'parent' sequence and AptaCluster-an aptamer clustering algorithm
      which is to our best knowledge, the only currently available tool capable of
      efficiently clustering entire aptamer pools. We applied these methods to an HT
      SELEX experiment developing aptamers against Interleukin 10 receptor alpha chain
      (IL-10RA) and experimentally confirmed our predictions thus validating our
      computational methods. 

PMID- 25870410
TI  - A serine-arginine-rich (SR) splicing factor modulates alternative splicing of
      over a thousand genes in Toxoplasma gondii.
AB  - Single genes are often subject to alternative splicing, which generates
      alternative mature mRNAs. This phenomenon is widespread in animals, and observed
      in over 90% of human genes. Recent data suggest it may also be common in
      Apicomplexa. These parasites have small genomes, and economy of DNA is
      evolutionarily favoured in this phylum. We investigated the mechanism of
      alternative splicing in Toxoplasma gondii, and have identified and localized
      TgSR3, a homologue of ASF/SF2 (alternative-splicing factor/splicing factor 2, a
      serine-arginine-rich, or SR protein) to a subnuclear compartment. In addition, we
      conditionally overexpressed this protein, which was deleterious to growth. qRT
      PCR was used to confirm perturbation of splicing in a known alternatively-spliced
      gene. We performed high-throughput RNA-seq to determine the extent of splicing
      modulated by this protein. Current RNA-seq algorithms are poorly suited to
      compact parasite genomes, and hence we complemented existing tools by writing a
      new program, GeneGuillotine, that addresses this deficiency by segregating
      overlapping reads into distinct genes. In order to identify the extent of
      alternative splicing, we released another program, JunctionJuror, that detects
      changes in intron junctions. Using this program, we identified about 2000 genes
      that were constitutively alternatively spliced in T. gondii. Overexpressing the
      splice regulator TgSR3 perturbed alternative splicing in over 1000 genes. 

PMID- 25870411
TI  - Major centers of motion in the large ribosomal RNAs.
AB  - Major centers of motion in the rRNAs of Thermus thermophilus are identified by
      alignment of crystal structures of EF-G bound and EF-G unbound ribosomal
      subunits. Small rigid helices upstream of these 'pivots' are aligned, thereby
      decoupling their motion from global rearrangements. Of the 21 pivots found, six
      are observed in the large subunit rRNA and 15 in the small subunit rRNA. Although
      the magnitudes of motion differ, with only minor exceptions equivalent pivots are
      seen in comparisons of Escherichia coli structures and one Saccharomyces
      cerevisiae structure pair. The pivoting positions are typically associated with
      structurally weak motifs such as non-canonical, primarily U-G pairs, bulge loops
      and three-way junctions. Each pivot is typically in direct physical contact with
      at least one other in the set and often several others. Moving helixes include
      rRNA segments in contact with the tRNA, intersubunit bridges and helices 28, 32
      and 34 of the small subunit. These helices are envisioned to form a network. EF-G
      rearrangement would then provide directional control of this network propagating
      motion from the tRNA to the intersubunit bridges to the head swivel or along the
      same path backward. 

PMID- 25870412
TI  - CWC22-dependent pre-mRNA splicing and eIF4A3 binding enables global deposition of
      exon junction complexes.
AB  - In metazoan cells, spliced mRNAs are marked by the exon junction complex (EJC), a
      multi-protein complex that serves as a key regulator of post-transcriptional mRNA
      metabolism. Deposition of EJCs on mRNA is intimately linked to the splicing
      process. The spliceosomal protein CWC22 directly binds the core EJC-protein
      eIF4A3, guides it to the spliceosome and initiates EJC assembly. In addition,
      CWC22 is involved in the splicing process itself, but the molecular details of
      its dual function remain elusive. Here we analyze the mechanisms, by which CWC22
      co-regulates pre-mRNA splicing and EJC assembly. We show that the core of CWC22
      is sufficient to mediate both pre-mRNA splicing and EJC assembly. Nonetheless,
      both processes can be functionally uncoupled with an eIF4A3-binding deficient
      mutant of CWC22, which impedes EJC assembly. A C-terminal domain of CWC22
      strongly enhances its spliceosomal interaction and likely regulates its function.
      High-throughput RNA-sequencing identifies global defects of pre-mRNA splicing and
      downregulation of diverse gene expression pathways in CWC22-depleted cells. We
      propose a model, in which CWC22 represents an integral component of the
      spliceosome and orchestrates pre-mRNA splicing and eIF4A3 binding to achieve
      global assembly of exon junction complexes. 

PMID- 25870413
TI  - Protein degradation and dynamic tRNA thiolation fine-tune translation at elevated
      temperatures.
AB  - Maintenance of protein quality control has implications in various processes such
      as neurodegeneration and ageing. To investigate how environmental insults affect
      this process, we analysed the proteome of yeast continuously exposed to mild heat
      stress. In agreement with previous transcriptomics studies, amongst the most
      marked changes, we found up-regulation of cytoprotective factors; a shift from
      oxidative phosphorylation to fermentation; and down-regulation of translation.
      Importantly, we also identified a novel, post-translationally controlled,
      component of the heat shock response. The abundance of Ncs2p and Ncs6p, two
      members of the URM1 pathway responsible for the thiolation of wobble uridines in
      cytoplasmic tRNAs tK(UUU), tQ(UUG) and tE(UUC), is down-regulated in a
      proteasomal dependent fashion. Using random forests we show that this results in
      differential translation of transcripts with a biased content for the
      corresponding codons. We propose that the role of this pathway in promoting
      catabolic and inhibiting anabolic processes, affords cells with additional time
      and resources needed to attain proper protein folding under periods of stress. 

PMID- 25870414
TI  - Functional interplay between the RK motif and linker segment dictates Oct4-DNA
      recognition.
AB  - The POU family transcription factor Oct4 plays pivotal roles in regulating
      pluripotency and somatic cell reprogramming. Previous studies have indicated an
      important role for major groove contacts in Oct4-DNA recognition; however, the
      contributions of the RK motif in the POUh domain and the linker segment joining
      the two DNA-binding domains remain poorly understood. Here, by combining
      molecular modelling and functional assays, we find that the RK motif is essential
      for Oct4-DNA association by recognizing the narrowed DNA minor groove.
      Intriguingly, computational simulations reveal that the function of the RK motif
      may be finely tuned by H-bond interactions with the partially disordered linker
      segment and that breaking these interactions significantly enhances the DNA
      binding and reprogramming activities of Oct4. These findings uncover a self
      regulatory mechanism for specific Oct4-DNA recognition and provide insights into
      the functional crosstalk at the molecular level that may illuminate mechanistic
      studies of the Oct protein family and possibly transcription factors in the POU
      family. Our gain-of-function Oct4 mutants might also be useful tools for use in
      reprogramming and regenerative medicine. 

PMID- 25870415
TI  - Improving small RNA-seq by using a synthetic spike-in set for size-range quality
      control together with a set for data normalization.
AB  - There is an increasing interest in complementing RNA-seq experiments with small
      RNA (sRNA) expression data to obtain a comprehensive view of a transcriptome.
      Currently, two main experimental challenges concerning sRNA-seq exist: how to
      check the size distribution of isolated sRNAs, given the sensitive size-selection
      steps in the protocol; and how to normalize data between samples, given the low
      complexity of sRNA types. We here present two separate sets of synthetic RNA
      spike-ins for monitoring size-selection and for performing data normalization in
      sRNA-seq. The size-range quality control (SRQC) spike-in set, consisting of 11
      oligoribonucleotides (10-70 nucleotides), was tested by intentionally altering
      the size-selection protocol and verified via several comparative experiments. We
      demonstrate that the SRQC set is useful to reproducibly track down biases in the
      size-selection in sRNA-seq. The external reference for data-normalization (ERDN)
      spike-in set, consisting of 19 oligoribonucleotides, was developed for sample-to
      sample normalization in differential-expression analysis of sRNA-seq data.
      Testing and applying the ERDN set showed that it can reproducibly detect
      differential expression over a dynamic range of 2(18). Hence, biological
      variation in sRNA composition and content between samples is preserved while
      technical variation is effectively minimized. Together, both spike-in sets can
      significantly improve the technical reproducibility of sRNA-seq. 

PMID- 25870416
TI  - Linker histone partial phosphorylation: effects on secondary structure and
      chromatin condensation.
AB  - Linker histones are involved in chromatin higher-order structure and gene
      regulation. We have successfully achieved partial phosphorylation of linker
      histones in chicken erythrocyte soluble chromatin with CDK2, as indicated by
      HPCE, MALDI-TOF and Tandem MS. We have studied the effects of linker histone
      partial phosphorylation on secondary structure and chromatin condensation.
      Infrared spectroscopy analysis showed a gradual increase of beta-structure in the
      phosphorylated samples, concomitant to a decrease in alpha-helix/turns, with
      increasing linker histone phosphorylation. This conformational change could act
      as the first step in the phosphorylation-induced effects on chromatin
      condensation. A decrease of the sedimentation rate through sucrose gradients of
      the phosphorylated samples was observed, indicating a global relaxation of the 30
      nm fiber following linker histone phosphorylation. Analysis of specific genes,
      combining nuclease digestion and qPCR, showed that phosphorylated samples were
      more accessible than unphosphorylated samples, suggesting local chromatin
      relaxation. Chromatin aggregation was induced by MgCl2 and analyzed by dynamic
      light scattering (DLS). Phosphorylated chromatin had lower percentages in volume
      of aggregated molecules and the aggregates had smaller hydrodynamic diameter than
      unphosphorylated chromatin, indicating that linker histone phosphorylation
      impaired chromatin aggregation. These findings provide new insights into the
      effects of linker histone phosphorylation in chromatin condensation. 

PMID- 25870417
TI  - Yaws: 110 years after Castellani's discovery of Treponema pallidum subspecies
      pertenue.
AB  - Yaws is a neglected infectious disease that affects mostly children and
      adolescents living in poor, rural communities in humid, tropical areas of Africa,
      southeast Asia, and the Pacific Islands. The etiological agent of yaws, Treponema
      pallidum subspecies pertenue (T. pertenue), was discovered by Aldo Castellani in
      1905 shortly after Schaudinn and Hoffmann discovered the etiological agent of
      syphilis, T. pallidum subspecies pallidum. The discovery of T. pertenue enabled
      the development of animal models and the identification of an effective
      antibiotic treatment (i.e., penicillin) for yaws. A World Health Organization
      (WHO) mass treatment campaign from 1952 to 1964 reduced the global burden of yaws
      by 95%, but failed to eradicate this disease. Today, 110 years after Castellani's
      discovery of T. pertenue, yaws is again targeted for eradication. Recent advances
      in the treatment and diagnosis of yaws improve the likelihood of success this
      time. However, several challenges must be overcome to make the goal of yaws
      eradication attainable. 

PMID- 25870418
TI  - Evaluation of point-of-contact circulating cathodic antigen assays for the
      detection of Schistosoma mansoni infection in low-, moderate-, and high
      prevalence schools in western Kenya.
AB  - We evaluated the performance of a point-of-contact circulating cathodic antigen
      assay (POC-CCA) to detect schistosome infections in primary school children (N =
      1,801) living in areas with low, moderate, and high Schistosoma mansoni
      prevalence in western Kenya. The commercially available assay (CCA-1) and a
      second, experimental formulation (CCA-2) were compared against Kato-Katz stool
      examinations and an anti-schistosome enzyme-linked immunosorbent assay (ELISA). A
      latent class model based on the four tests was used to establish "true infection
      status" in three different zones based on their distance from Lake Victoria. As a
      screening tool for community treatment according to World Health Organization
      (WHO) guidelines, the Kato-Katz examination was in closest agreement with the
      latent class model, followed by the experimental CCA-2, soluble adult worm
      antigen preparation (SWAP) ELISA, and CCA-1, which had high sensitivity compared
      with the other tests but was consistently the least specific. Our experience
      suggests that POC-CCA tests offer a field-friendly alternative to Kato-Katz, but
      need further interpretation for appropriate field use. 

PMID- 25870419
TI  - Serological investigation of heartland virus (Bunyaviridae: Phlebovirus) exposure
      in wild and domestic animals adjacent to human case sites in Missouri 2012-2013.
AB  - Heartland virus (HRTV; Bunyaviridae: Phlebovirus) has recently emerged as a
      causative agent of human disease characterized by thrombocytopenia and leukopenia
      in the United States. The lone star tick (Amblyomma americanum L.) has been
      implicated as a vector. To identify candidate vertebrate amplification hosts
      associated with enzootic maintenance of the virus, sera and ticks were sampled
      from 160 mammals (8 species) and 139 birds (26 species) captured near 2 human
      case residences in Andrew and Nodaway Counties in northwest Missouri. HRTV
      specific neutralizing antibodies were identified in northern raccoons (42.6%),
      horses (17.4%), white-tailed deer (14.3%), dogs (7.7%), and Virginia opossums
      (3.8%), but not in birds. Virus isolation attempts from sera and ticks failed to
      detect HRTV. The high antibody prevalence coupled with local abundance of white
      tailed deer and raccoons identifies these species as candidate amplification
      hosts. 

PMID- 25870420
TI  - Madariaga virus infection associated with a case of acute disseminated
      encephalomyelitis.
AB  - We present the first report of a pediatric case of acute disseminated
      encephalomyelitis (ADEM) associated with Madariaga virus infection (MADV,
      Alphavirus, Togaviridae; formerly known as South American variants of eastern
      equine encephalitis virus [EEEV]) in a patient of the 2010 alphaviral epidemic
      reported in Panama. The patient was admitted to the Hospital del Nino in Panama
      City with suspected meningitis, exhibited with decreased alertness and
      disorientation in space and time, hemiparesis, and left Babinski sign. The
      patient was transferred to the intensive care unit and treated with aciclovir and
      methylprednisolone. The magnetic resonance imaging (MRI) of the brain revealed
      multiple hyperintense lesions at T2-weighted images (T2) and fluid-attenuated
      inversion recovery (FLAIR) on the cortical-subcortical level. Sera samples
      obtained on days 6 and 12 were immunoglobulin M (IgM) positive for MADV. The
      findings on the clinical and cerebrospinal analyses, rapid symptom progression as
      well as neuroimaging, and serologic studies support our diagnosis. Our results
      suggest that MADV should be included in the etiologic differential diagnosis of
      ADEM in endemic countries. 

PMID- 25870421
TI  - Human fascioliasis: a re-emerging disease in upper Egypt.
AB  - In recent years, the number of humans infected with Fasciola has risen rapidly.
      Diagnosis is based mainly on detection of eggs in stool analysis. The rate of
      infection in Egypt is unknown. In this retrospective study, we describe 23 cases
      of hepatic fascioliasis, and only 2 of these cases showed eggs in stools. The
      symptoms of infection, such as pyrexia of unknown origin, epigastric pain, and
      abdominal distension, were suggestive. Imaging techniques, including abdominal
      ultrasonography and computed tomography, were very helpful in detecting hepatic
      changes. An indirect hemagglutination assay proved to be of value for diagnosis.
      Treatment using a 2-day triclabendazole regimen cured the infection and signs of
      hepatic involvement disappeared. Combining both imaging techniques and laboratory
      tests is essential for diagnosis of fascioliasis in the early stage. 

PMID- 25870422
TI  - Cost analysis of tests for the detection of Schistosoma mansoni infection in
      children in western Kenya.
AB  - Financial resources tend to be limited in schistosomiasis endemic areas, forcing
      program managers to balance financial and scientific considerations when
      selecting detection assays. Therefore, we compared the costs of using single
      stool Kato-Katz, triplicate stool Kato-Katz, and point-of-contact circulating
      cathodic antigen (POC-CCA) assays for the detection of Schistosoma mansoni
      infection. Economic and financial costs were estimated from the viewpoint of a
      schistosomiasis control program using the ingredients approach. Costs related to
      specimen collection, sample processing and analysis, and treatment delivery were
      considered. Analysis inputs and assumptions were tested using one-way and two-way
      sensitivity analysis. The total per-person cost of performing the single Kato
      Katz, triplicate Kato-Katz, and POC-CCA was US$6.89, US$17.54, and US$7.26,
      respectively. Major cost drivers included labor, transportation, and supplies. In
      addition, we provide a costing tool to guide program managers in evaluating
      detection costs in specific settings, as costs may vary temporally and spatially.

PMID- 25870423
TI  - Quantitation of Blomia tropicalis allergen Blo t 5 in cereal and cereal-based
      foods consumed in the Nile Delta, Egypt.
AB  - The mite Blomia tropicalis has significant prevalence worldwide. Blo t 5 is a
      major B. tropicalis allergen that has been associated with sensitization and
      allergic symptoms in many asthmatic patients. Besides house dust, contaminated
      foodstuffs are an important source of exposure to B. tropicalis allergens. In
      this study, a double sandwich enzyme-linked immunosorbent assay (ELISA) using mAb
      4D4 and biotinylated mAb 4G9 was done to detect Blo t 5 allergen in different
      types of raw and processed foods, including wheat, corn, rice, bean, wheat and
      corn flour, cake, and rusk, which were collected from retail stores in the Nile
      Delta of Egypt. Out of 88 samples, 38 (43.2%) were positive for Blo t 5 allergen
      with no significant statistical difference in positivity according to food type.
      In positive samples, the Blo t 5 concentration ranged from 10 ng/g to 790 ng/g.
      This study showed that Blo t 5 should be considered as an important allergen that
      presents a risk to the Egyptian population and should become a routine allergen
      in the skin prick test to improve the management of allergic disease. 

PMID- 25870424
TI  - Evidence of limited polyandry in a natural population of Aedes aegypti.
AB  - The mosquito Aedes aegypti is a vector of yellow fever, dengue, and chikungunya.
      Control of the insect is crucial to stop the spread of dengue and chikungunya, so
      it is critically important to understand its mating behavior. Primarily, based on
      laboratory behavior, it has long been assumed that Ae. aegypti females mate once
      in their lifetime. However, multiple inseminations have been observed in semi
      field and laboratory settings, and in closely related species. Here, we report
      the first evidence of polyandry in a natural population of Ae. aegypti. Female
      Ae. aegypti were captured around the New Orleans, LA, metropolitan area. They
      were offered a blood meal and allowed to lay eggs, which were reared to the third
      instar larval stage. A parentage analysis using four microsatellite loci was
      performed. Out of 48 families, 3 showed evidence of multiple paternity. An
      expanded analysis of these three families found that one family group included
      offspring contributed by three fathers, and the other two included offspring from
      two fathers. This result establishes that polyandry can occur in a small
      proportion of Ae. aegypti females in a natural setting. This could complicate
      future genetic control efforts and has implications for sampling for population
      genetics. 

PMID- 25870425
TI  - Observed practices and perceived advantages of different hand cleansing agents in
      rural Bangladesh: ash, soil, and soap.
AB  - Bangladeshi communities have historically used ash and soil as handwashing
      agents. A structured observation study and qualitative interviews on the use of
      ash/soil and soap as handwashing agents were conducted in rural Bangladesh to
      help develop a handwashing promotion intervention. The observations were
      conducted among 1,000 randomly selected households from 36 districts.
      Fieldworkers observed people using ash/soil to wash their hand(s) on 13% of
      occasions after defecation and on 10% after cleaning a child's anus. This
      compares with 19% of people who used soap after defecation and 27% after cleaning
      a child who defecated. Using ash/soil or soap was rarely (< 1%) observed at other
      times recommended for handwashing. The qualitative study enrolled 24 households
      from three observation villages, where high usage of ash/soil for handwashing was
      detected. Most informants reported that ash/soil was used only for handwashing
      after fecal contact, and that ash/soil could clean hands as effectively as soap. 

PMID- 25870426
TI  - Intraventricular Taenia solium cysts presenting with Bruns syndrome and
      indications for emergent neurosurgery.
AB  - Bruns syndrome is an unusual phenomenon, characterized by attacks of sudden and
      severe headache, vomiting, and vertigo, triggered by abrupt movement of the head.
      The presumptive cause of Bruns syndrome is a mobile deformable intraventricular
      mass leading to an episodic obstructive hydrocephalus. Intraventricular tumors
      have been associated with Bruns syndrome; however, few cases of intraventricular
      neurocysticercosis have been reported to present with Bruns syndrome. We report
      the first series of fourth ventricular neurocysticercosis presenting with Bruns
      syndrome in the United States and review the other published cases where surgery
      was indicated. 

PMID- 25870427
TI  - Exploring the contribution of host susceptibility to epidemiological patterns of
      Schistosoma japonicum infection using an individual-based model.
AB  - We recently reported the analysis of epidemiological data suggesting variability
      in individual susceptibility to infection by Schistosoma japonicum among rural
      villagers who reside in Sichuan Province of southwestern China. By supplementing
      the data used in the earlier analysis from other studies we have reported from
      this region, we presented improved estimates of cercarial exposure, which in
      turn, result in stronger evidence of susceptibility. This analysis was conducted
      using an individual-based mathematical model (IBM) whose use was motivated by the
      nature and extent of field data from the low-transmission environments
      exemplified by one of our datasets and typical of the current situation in most
      endemic areas of China. In addition to individual susceptibility and water
      contact, the model includes stochastic aspects of cercarial exposure as well as
      of diagnostic procedures, the latter being particularly relevant to the low
      transmission environment. The simulation studies show that, to produce key
      aspects of the epidemiological findings, the distribution of susceptibility
      ranges over several orders of magnitude and is highly right skewed. We found no
      compelling evidence that the distribution of susceptibility differed between the
      two populations that underlie both the epidemiological and simulation results. 

PMID- 25870428
TI  - Human granulocytic anaplasmosis in the United States from 2008 to 2012: a summary
      of national surveillance data.
AB  - Human granulocytic anaplasmosis is an acute, febrile illness transmitted by the
      ticks Ixodes scapularis and Ixodes pacificus in the United States. We present a
      summary of passive surveillance data for cases of anaplasmosis with onset during
      2008-2012. The overall reported incidence rate (IR) was 6.3 cases per million
      person-years. Cases were reported from 38 states and from New York City, with the
      highest incidence in Minnesota (IR = 97), Wisconsin (IR = 79), and Rhode Island
      (IR = 51). Thirty-seven percent of cases were classified as confirmed, almost
      exclusively by polymerase chain reaction. The reported case fatality rate was
      0.3% and the reported hospitalization rate was 31%. IRs, hospitalization rates,
      life-threatening complications, and case fatality rates increased with age group.
      The IR increased from 2008 to 2012 and the geographic range of reported cases of
      anaplasmosis appears to have increased since 2000-2007. Our findings are
      consistent with previous case series and recent reports of the expanding range of
      the tick vector I. scapularis. 

PMID- 25870429
TI  - Poor housing construction associated with increased malaria incidence in a cohort
      of young Ugandan children.
AB  - Despite the use of accepted interventions to combat malaria, such as insecticide
      treated bed nets and artemisinin-based combination therapy, malaria remains a
      leading cause of morbidity and mortality in Uganda. We investigated associations
      between household factors and malaria incidence in a cohort of children living in
      a highly endemic region of Uganda. Living in a modern house, defined as the use
      of non-earth floors, non-thatched roofs, and non-mud walls, was associated with
      approximately half malaria incidence compared with living in a traditional home
      (incidence rate ratio [IRR] = 0.54, P = 0.001). Other factors found to be
      associated with a lower incidence of malaria included living in town versus rural
      setting; sleeping in a room with openings to the outside (windows, eaves, and
      airbricks); and having an older and more educated primary caregiver. This study
      adds to the growing body of evidence that improved house construction may be
      associated with a lower risk of malaria. 

PMID- 25870431
TI  - Binary-Encounter-Bethe ionisation cross sections for simulation of DNA damage by
      the direct effect of ionising radiation.
AB  - DNA damage is of crucial importance in the understanding of the effects of
      ionising radiation. To refine existing DNA damage models, an approach using the
      Binary-Encounter-Bethe (BEB) cross sections was developed. The differential cross
      sections for ionisation of the molecular orbitals of the DNA bases, sugars and
      phosphates are calculated using the electron binding energy, the mean kinetic
      energy and the occupancy number of each orbital as parameters. The resulting
      cross section has an analytic form which is quite convenient to use for Monte
      Carlo codes that randomly sample the energy loss occurring during an ionisation
      event. We also describe an algorithm to simulate the interactions of electrons
      with DNA in the radiation transport code RITRACKS using the integrated BEB cross
      section for the bases, sugar and phosphates. 

PMID- 25870430
TI  - Information to act: household characteristics are predictors of domestic
      infestation with the Chagas vector Triatoma dimidiata in Central America.
AB  - The interruption of vectorial transmission of Chagas disease by Triatoma
      dimidiata in central America is a public health challenge that cannot be resolved
      by insecticide application alone. In this study, we collected information on
      previously known household risk factors for infestation in 11 villages and more
      than 2,000 houses in Guatemala, Honduras, and El Salvador, and we constructed
      multivariate models and used multimodel inference to evaluate their importance as
      predictors of infestation in the region. The models had moderate ability to
      predict infested houses (sensitivity, 0.32-0.54) and excellent ability to predict
      noninfested houses (specificity higher than 0.90). Predictive ability was
      improved by including random village effects and presence of signs of infestation
      (insect feces, eggs, and exuviae) as fixed effects. Multimodel inference results
      varied depending on factors included, but house wall materials (adobe, bajareque,
      and palopique) and signs of infestation were among the most important predictive
      factors. Reduced models were not supported suggesting that all factors
      contributed to predictions. Previous knowledge and information from this study
      show that we have evidence to prioritize rural households for improvement to
      prevent house infestation with Triatoma dimidiata in Central America. House
      improvement will most likely have other health co-benefits. 

PMID- 25870432
TI  - The ANDANTE project: a multidisciplinary approach to neutron RBE.
AB  - The usual method for estimating the risk from exposure to neutrons uses the
      concept of relative biological effectiveness (RBE) compared with the risk from
      photons, which is better known. RBE has been evaluated using cellular and animal
      models. But this causes difficulties in applying the concept to humans. The
      ANDANTE project takes a new approach using three different disciplines in
      parallel: Physics: a track structure model is used to contrast the patterns of
      damage to cellular macro-molecules from neutrons compared with photons. The
      simulations reproduce the same energy spectra as are used in the other two
      approaches. Stem cell radiobiology: stem cells from thyroid, salivary gland and
      breast tissue are given well characterised exposures to neutrons and photons. A
      number of endpoints are used to estimate the relative risk of damage from
      neutrons compared with photons. Irradiated cells will also be transplanted into
      mice to investigate the progression of the initial radiation effects in stem
      cells into tumours in a physiological environment. EPIDEMIOLOGY: the relative
      incidence rates of second cancers of the thyroid, salivary gland and breast
      following paediatric radiotherapy (conventional radiotherapy for photons and
      proton therapy for neutrons) are investigated in a pilot single-institution
      study, exploring the possible design of a multi-institution prospective study
      comparing the long-term out-of-field and in-field effects of scanned and
      scattered protons. The results will be used to validate an RBE-based risk model
      developed by the project, and validate the corresponding RBE values.

PMID- 25870434
TI  - European activities in radiation protection in medicine.
AB  - The recently published Council Directive 2013/59/Euratom ('new European Basic
      Safety Standards', EU BSS) modernises and consolidates the European radiation
      protection legislation by taking into account the latest scientific knowledge,
      technological progress and experience with implementing the current legislation
      and by merging five existing Directives into a single piece of legislation. The
      new European BSS repeal previous European legislation on which the national
      systems for radiation protection in medicine of the 28 European Union (EU) Member
      States are based, including the 96/29/Euratom 'BSS' and the 97/43/Euratom
      'Medical Exposure' Directives. While most of the elements of the previous
      legislation have been kept, there are several legal changes that will have
      important influence over the regulation and practice in the field all over Europe
      these include, among others: (i) strengthening the implementation of the
      justification principle and expanding it to medically exposed asymptomatic
      individuals, (ii) more attention to interventional radiology, (iii) new
      requirements for dose recording and reporting, (iv) increased role of the medical
      physics expert in imaging, (v) new set of requirements for preventing and
      following up on accidents and (vi) new set of requirements for procedures where
      radiological equipment is used on people for non-medical purposes (non-medical
      imaging exposure). The EU Member States have to enforce the new EU BSS before
      January 2018 and bring into force the laws, regulations and administrative
      provisions necessary to comply with it. The European Commission has certain legal
      obligations and powers to verify the compliance of the national measures with the
      EU laws and, wherever necessary, issue recommendations to, or open infringement
      cases against, national governments. In order to ensure timely and coordinated
      implementation of the new European legal requirements for radiation protection,
      the Commission is launching several actions including promotion and dissemination
      activities, exchange and discussion fora and provision of guidance. These actions
      will be based on previous experiences and will rely on the results of recent and
      ongoing EU-funded projects. Important stakeholders including the Euratom Article
      31 Group, the association of the Heads of European Radiological protection
      Competent Authorities (HERCA) and different European professional and specialty
      organisations will be involved. 

PMID- 25870433
TI  - Radiosensitivity in lymphoblastoid cell lines derived from Shwachman-Diamond
      syndrome patients.
AB  - Shwachman-Diamond syndrome is an autosomal-recessive disorder characterised by
      bone marrow failure and a cumulative risk of progression to acute myeloid
      leukaemia. The Shwachman-Bodian-Diamond syndrome (SBDS) gene, the only gene known
      to be causative of the pathology, is involved in ribosomal biogenesis, stress
      responses and DNA repair, and the lack of SBDS sensitises cells to many stressors
      and leads to mitotic spindle destabilisation. The effect of ionising radiation on
      SBDS-deficient cells was investigated using immortalised lymphocytes from SDS
      patients in comparison with positive and negative controls in order to test
      whether, in response to ionising radiation exposure, any impairment in the DNA
      repair machinery could be observed. After irradiating cells with different doses
      of X-rays or gamma-rays, DNA repair kinetics and the residual damages using the
      alkaline COMET assay and the gamma-H2AX assay were assessed, respectively. In
      this work, preliminary data about the comparison between ionising radiation
      effects in different patients-derived cells and healthy control cells are
      presented. 

PMID- 25870435
TI  - Microbeam-coupled capillary electrophoresis.
AB  - Within the first few microseconds following a charged particle traversal of a
      cell, numerous oxygen and nitrogen radicals are formed along the track. Presented
      here is a method, using capillary electrophoresis, for simultaneous measurement,
      within an individual cell, of specific reactive oxygen species, such as the
      superoxide radical ([Formula: see text]) as well as the native and oxidised forms
      of glutathione, an ubiquitous anti-oxidant that assists the cell in coping with
      these species. Preliminary data are presented as well as plans for integrating
      this system into the charged particle microbeam at Columbia University. 

PMID- 25870436
TI  - Radiation exposure to patients and medical staff in hepatic chemoembolisation
      interventional procedures in Recife, Brazil.
AB  - The purpose of this study was to evaluate patient and medical staff absorbed
      doses received from transarterial chemoembolisation of hepatocellular carcinoma,
      which is the most common primary liver tumour worldwide. The study was performed
      in three hospitals in Recife, capital of the state of Pernambuco, located in the
      Brazilian Northeastern region. Two are public hospitals (A and B), and one is
      private (C). For each procedure, the number of images, irradiation parameters
      (kV, mA and fluoroscopy time), the air kerma-area product (PKA) and the
      cumulative air kerma (Ka,r) at the reference point were registered. The maximum
      skin dose (MSD) of the patient was estimated using radiochromic film. For the
      medical staff dosimetry, thermoluminescence dosemeters (TLD-100) were attached
      next to the eyes, close to the thyroid (above the shielding), on the thorax under
      the apron, on the wrist and on the feet. The effective dose to the staff was
      estimated using the algorithm of von Boetticher. The results showed that the mean
      value of the total PKA was 267.49, 403.83 and 479.74 Gy cm(2) for Hospitals A, B
      and C, respectively. With regard to the physicians, the average effective dose
      per procedure was 17 uSv, and the minimum and maximum values recorded were 1 and
      41 uSy, respectively. The results showed that the feet received the highest doses
      followed by the hands and lens of the eye, since the physicians did not use
      leaded glasses and the equipment had no lead curtain. 

PMID- 25870437
TI  - A dosimetric study of prostate brachytherapy using Monte Carlo simulations with a
      voxel phantom, measurements and a comparison with a treatment planning procedure.
AB  - In prostate brachytherapy treatments, there is an initial swelling of the
      prostate of the patient due to an oedema related to the insertion of the seeds.
      The variation of the prostate volume can lead to variations in the final
      prescribed dose in treatment planning procedures. As such, it is important to
      understand their influence for dose optimisation purposes. This work reports on a
      dosimetric study of the swelling of the prostate in prostate brachytherapy using
      Monte Carlo simulations. Dosimetric measurements performed on a physical
      anthropomorphic tissue-equivalent prostate phantom and thermoluminescent
      dosimeters (TLDs) were used to validate the MC model. Finally the MC model was
      also used to simulate prostate swelling in a real treatment planning procedure.
      The obtained results indicate that the parameters mentioned above represent a
      source of uncertainty in dose assessment in prostate brachytherapy, and can be
      detrimental to a correct dose evaluation in treatment plannings, and that these
      parameters can be accurately determined by means of MC simulations with a voxel
      phantom. 

PMID- 25870438
TI  - Real-time observation of irradiated HeLa-cell modified by fluorescent
      ubiquitination-based cell-cycle indicator using synchrotron X-ray microbeam.
AB  - Fluorescent ubiquitination-based cell-cycle indicator (FUCCI) human cancer (HeLa)
      cells (red indicates G1; green, S/G2) were exposed to a synchrotron X-ray
      microbeam. Cells in either G1 or S/G2 were irradiated selectively according to
      their colour in the same microscopic field. Time-lapse micrographs of the
      irradiated cells were acquired for 24 h after irradiation. For fluorescent
      immunostaining, phosphorylated histone proteins (gamma-H2AX) indicated the
      induction of DNA double-strand breaks. The cell cycle was arrested by irradiation
      at S/G2. In contrast, cells irradiated at G1 progressed to S/G2. The foci were
      induced in cells irradiated at both G1 and S/G2, suggesting that the G1-S (or S)
      checkpoint pathway does not function in HeLa cells due to the fact that the cells
      are functionally p53 deficient, even though X-ray microbeam irradiation
      significantly induces double-strand breaks. These results demonstrate that single
      FUCCI cell exposure and live cell imaging are powerful methods for studying the
      effects of radiation on the cell cycle. 

PMID- 25870440
TI  - RANZCP Abstracts.

PMID- 25870439
TI  - Cardiac and electro-cortical concomitants of social feedback processing in women.
AB  - This study provides a joint analysis of the cardiac and electro-cortical-early
      and late P3 and feedback-related negativity (FRN)-responses to social acceptance
      and rejection feedback. Twenty-five female participants performed on a social-
      and age-judgment control task, in which they received feedback with respect to
      their liking and age judgments, respectively. Consistent with previous reports,
      results revealed transient cardiac slowing to be selectively prolonged to
      unexpected social rejection feedback. Late P3 amplitude was more pronounced to
      unexpected relative to expected feedback. Both early and late P3 amplitudes were
      shown to be context dependent, in that they were more pronounced to social as
      compared with non-social feedback. FRN amplitudes were more pronounced to
      unexpected relative to expected feedback, irrespective of context and feedback
      valence. This pattern of findings indicates that social acceptance and rejection
      feedback have widespread effects on bodily state and brain function, which are
      modulated by prior expectancies. 

PMID- 25870442
TI  - Reflections on the lessons of the recent endovascular stroke trials.

PMID- 25870443
TI  - Myxedema madness: a case for short-term antipsychotics?

PMID- 25870444
TI  - Akathisia with azithromycin.

PMID- 25870445
TI  - Metoclopramide-induced asystolic cardiac arrest.

PMID- 25870446
TI  - Comment: clinical experience with prophylactic fondaparinux in critically ill
      patients with moderate to severe renal impairment or renal failure requiring
      renal replacement therapy.

PMID- 25870447
TI  - Reply: clinical experience with prophylactic fondaparinux in critically ill
      patients with moderate to severe renal impairment or renal failure requiring
      renal replacement therapy.

PMID- 25870448
TI  - Ceftriaxone-induced immune hemolytic anemia.
AB  - Neuman, G, Boodhan, S, Wurman, I, et al. Ceftriaxone-induced immune hemolytic
      anemia. Ann Pharmacother. 2014;48:1594-1604. doi: 10.1177/1060028014548310. On
      page 1599 of the above article, lines 12-13 in the left column, there is a
      sentence which reads: "In the subgroup of children, 64% of the cases were fatal."
      This sentence should have read: "Sixty-four percent of these fatalities were
      children." 

PMID- 25870449
TI  - Opportunities and Constraints in Disseminating Qualitative Research in Web 2.0
      Virtual Environments.
AB  - The Web 2.0 digital environment is revolutionizing how users communicate and
      relate to each other, and how information is shared, created, and recreated
      within user communities. The social media technologies in the Web 2.0 digital
      ecosystem are fundamentally changing the opportunities and dangers in
      disseminating qualitative health research. The social changes influenced by
      digital innovations shift dissemination from passive consumption to user
      centered, apomediated cooperative approaches, the features of which are
      underutilized by many qualitative researchers. We identify opportunities new
      digital media presents for knowledge dissemination activities including access to
      wider audiences with few gatekeeper constraints, new perspectives, and symbiotic
      relationships between researchers and users. We also address some of the
      challenges in embracing these technologies including lack of control, potential
      for unethical co-optation of work, and cyberbullying. Finally, we offer solutions
      to enhance research dissemination in sustainable, ethical, and effective
      strategies. 

PMID- 25870450
TI  - Epilepsy in developing countries: perspectives from India.

PMID- 25870451
TI  - Signal hyperintensity of the callosum after ventriculoperitoneal shunting.

PMID- 25870452
TI  - Ossifying fibroma of the maxilla and tuberous sclerosis complex.

PMID- 25870453
TI  - Clinical Reasoning: a puzzling case of amnesia.

PMID- 25870454
TI  - Growth hormone treatment for childhood short stature and risk of stroke in early
      adulthood; adult stroke risk after growth hormone treatment in childhood: first
      do no harm.

PMID- 25870455
TI  - Memory fMRI predicts verbal memory decline after anterior temporal lobe
      resection.

PMID- 25870456
TI  - Clinical reasoning: novel GLUT1-DS mutation: refractory seizures and ataxia.
AB  - Intractable epilepsy is a common diagnosis among child neurology practitioners
      with medical management remaining unsatisfactory in many cases. GLUT1 deficiency
      syndrome (GLUT1-DS) is a disorder that should be considered in such situations.
      Evaluation by comparing serum to CSF glucose levels is a fast and relatively easy
      test, with hypoglycorrhachia being highly suggestive of GLUT1-DS. Furthermore,
      treatment with the ketogenic diet is well-established and can result in
      significant improvement in quality of life for these patients. The following case
      report outlines the presentation of one such patient and highlights common
      features that can be seen with GLUT1-DS. Of interest, she was found to have a
      spontaneous, novel mutation that has not been reported previously. Her case
      allows us to expand on the present literature and demonstrate the improvements
      that can be seen in a child with appropriate treatment. 

PMID- 25870457
TI  - Teaching neuroImages: a broadly distributed ictal rhythm easily missed on bipolar
      montage: "now you see it...".

PMID- 25870458
TI  - Teaching neuroImages: short stature, imperforate anus, and polydactyly: When is a
      hypothalamic mass an incidentaloma?

PMID- 25870459
TI  - Microwave Induced Reactive Base Wash for the Removal of Oxidation Debris from
      Carboxylated Carbon Nanotubes.
AB  - Removal of oxidation debris for generating high purity functionalized carbon
      nanotubes (CNTs) has been a challenge, where base washing has been found to be an
      effective purification treatment. In this paper we report microwave induced
      reactive base wash (MRW) as a fast, green alternate to conventional filtrate
      washing. Carboxylated CNTs of three different dimensions were subjected to MRW
      and the results were compared to conventional base-wash. The results showed that
      MRW was an effective method for the removal of oxidation debris which reduced the
      reaction time from 4 hours to 20 min and alkali consumption by 75%. The CNTs from
      MRW were similar to those from conventional base wash in terms of dimensions,
      elemental composition, BET surface area and colloidal stability in aqueous media.

PMID- 25870460
TI  - In Vitro Degradation of an Aromatic Polyanhydride with Enhanced Thermal
      Properties.
AB  - Polyanhydrides have been studied as a drug delivery vehicles due to their surface
      eroding behavior which results in zero-order release. However, many polyanhyrides
      have thermal and solubility properties that make them difficult to formulate for
      these applications. Poly[alpha,alpha'-bis(ortho-carboxyphenoxy)-para-xylene]
      (oCPX) is an aromatic polyanhydride that has thermal and solubility properties
      enabling facile processing. The polymer's in vitro degradation profile exhibited
      an induction period up to 10 days in which degradation product concentration in
      the media was minimal, followed by a period of stable release of the
      biocompatible degradation product. Scanning electron microscope images and
      molecular weight changes of the polymer matrices confirm that this polymer is
      primarily surface-eroding. The combination of thermal properties, solubility,
      polymer degradation time, and erosion mechanism indicate that poly(oCPX) is be a
      suitable matrix candidate for extended, controlled drug delivery.

PMID- 25870461
TI  - Interactive Effects of Anxiety Sensitivity and Difficulties in Emotion
      Regulation: An Examination among Individuals in Residential Substance Use
      Treatment with Comorbid Posttraumatic Stress Disorder.
AB  - Individuals with posttraumatic stress disorder (PTSD) exhibit deficits in
      cognitive and emotional processes. PTSD severity is positively associated with
      anxiety sensitivity (AS) and difficulties in emotion regulation, and difficulties
      in emotion regulation mediate the relation between AS and PTSD. However, previous
      research has not examined the interactive nature of these variables. Associations
      between PTSD, AS, and difficulties in emotion regulation were examined in
      patients with PTSD in a residential substance treatment program (N = 120).
      Conditional process analyses indicated an interactive effect of difficulties in
      emotion regulation and AS for predicting PTSD symptom severity. For individuals
      high in emotion regulation difficulties, PTSD symptom severity was high
      regardless of level of AS; conversely, for individuals high in AS, increased PTSD
      severity was observed regardless of level of emotion regulation difficulties.
      Results suggest directions for future research, including targeting patient
      specific cognitive-affective processes to enhance PTSD treatment response among
      substance dependent individuals.

PMID- 25870462
TI  - Generalized species sampling priors with latent Beta reinforcements.
AB  - Many popular Bayesian nonparametric priors can be characterized in terms of
      exchangeable species sampling sequences. However, in some applications,
      exchangeability may not be appropriate. We introduce a novel and
      probabilistically coherent family of non-exchangeable species sampling sequences
      characterized by a tractable predictive probability function with weights driven
      by a sequence of independent Beta random variables. We compare their theoretical
      clustering properties with those of the Dirichlet Process and the two parameters
      Poisson-Dirichlet process. The proposed construction provides a complete
      characterization of the joint process, differently from existing work. We then
      propose the use of such process as prior distribution in a hierarchical Bayes
      modeling framework, and we describe a Markov Chain Monte Carlo sampler for
      posterior inference. We evaluate the performance of the prior and the robustness
      of the resulting inference in a simulation study, providing a comparison with
      popular Dirichlet Processes mixtures and Hidden Markov Models. Finally, we
      develop an application to the detection of chromosomal aberrations in breast
      cancer by leveraging array CGH data.

PMID- 25870463
TI  - Semi-automatic ground truth generation using unsupervised clustering and limited
      manual labeling: Application to handwritten character recognition.
AB  - For training supervised classifiers to recognize different patterns, large data
      collections with accurate labels are necessary. In this paper, we propose a
      generic, semi-automatic labeling technique for large handwritten character
      collections. In order to speed up the creation of a large scale ground truth, the
      method combines unsupervised clustering and minimal expert knowledge. To exploit
      the potential discriminant complementarities across features, each character is
      projected into five different feature spaces. After clustering the images in each
      feature space, the human expert labels the cluster centers. Each data point
      inherits the label of its cluster's center. A majority (or unanimity) vote
      decides the label of each character image. The amount of human involvement
      (labeling) is strictly controlled by the number of clusters - produced by the
      chosen clustering approach. To test the efficiency of the proposed approach, we
      have compared, and evaluated three state-of-the art clustering methods (k-means,
      self-organizing maps, and growing neural gas) on the MNIST digit data set, and a
      Lampung Indonesian character data set, respectively. Considering a k-nn
      classifier, we show that labeling manually only 1.3% (MNIST), and 3.2% (Lampung)
      of the training data, provides the same range of performance than a completely
      labeled data set would.

PMID- 25870464
TI  - Direct-to-Consumer Racial Admixture Tests and Beliefs About Essential Racial
      Differences.
AB  - Although at first relatively disinterested in race, modern genomic research has
      increasingly turned attention to racial variations. We examine a prominent
      example of this focus-direct-to-consumer racial admixture tests-and ask how
      information about the methods and results of these tests in news media may affect
      beliefs in racial differences. The reification hypothesis proposes that by
      emphasizing a genetic basis for race, thereby reifying race as a biological
      reality, the tests increase beliefs that whites and blacks are essentially
      different. The challenge hypothesis suggests that by describing differences
      between racial groups as continua rather than sharp demarcations, the results
      produced by admixture tests break down racial categories and reduce beliefs in
      racial differences. A nationally representative survey experiment (N = 526)
      provided clear support for the reification hypothesis. The results suggest that
      an unintended consequence of the genomic revolution may be to reinvigorate age
      old beliefs in essential racial differences.

PMID- 25870465
TI  - Children's Social Desirability: Effects of Test Assessment Mode.
AB  - This study examined a recently developed short version of the Children's Social
      Desirability (CSD-S) scale with 157 fourth-grade children. Of interest was a)
      whether one-month test-retest reliability would vary as a function of test
      assessment mode (interview or classroom), gender, race, SES, and BMI percentile,
      and b) whether the degree of social desirability would vary as a function of
      these same variables. The CSD-S scale showed good test-retest reliability for
      both interview and classroom assessment modes (.85 and .83, respectively).
      Internal consistency also was good (first interview administration = .84; first
      classroom administration = .81). Reliability was good and did not vary
      significantly over assessment mode or any child subgroup variables, suggesting
      that the CSD-S scale is appropriate for general use. The interview mode elicited
      significantly more socially desirable answers than did the classroom mode. Social
      desirability did not differ across child subgroups. Some of these findings were
      examined, and replicated, on another sample. Thus, the CSD-S scale may be used
      with diverse groups of children to a) reliably assess a social desirability bias
      that may systematically bias other self-reports of interest to researchers and b)
      examine individual differences in degree of social desirability.

PMID- 25870466
TI  - Medical Archives is Now Indexed in Pubmed Central.

PMID- 25870467
TI  - Prognostic value of anatomical dominance of coronary circulation in patients with
      surgical myocardial revascularization.
AB  - INTRODUCTION: This study evaluated the frequency of domination of the coronary
      arteries types in patients treated by surgical myocardial revascularization. The
      aim of the study was to determine whether the left coronary circulation dominance
      is a prognostic factor for poorer outcome in patients undergoing coronary artery
      bypass surgery. MATERIAL AND METHODS: A total sample consisted of 100 patients
      with coronary artery disease that were treated with coronary artery bypass
      grafting at the Clinic for Cardiac Surgery, Clinical Center of the University of
      Sarajevo. To all patients on the basis of preoperative coronary angiography was
      determined the dominance of the coronary arteries. Patients included in the study
      were divided into two groups, with the left and right with coronary dominance.
      RESULTS: Left coronary dominance in a sample of patients was present in 21/100
      (21%), right in 69/100 (69%) and balanced in 10/100 (10%) cases. Female gender
      was significantly more frequent in patients with left coronary dominance and
      proved to be a stronger predictor of poorer outcome, especially in combination
      with left main stenosis of the left coronary artery and left coronary dominance.
      Inability of revascularization of the r. interventricularis posterior (RIVP) was
      statistically significantly higher in case of left dominance 9/21 (42.9%),
      compared to the right 16/79 (20.3%), p=0.033. Lethal outcome was more common in
      case of left dominance in relation to the right (9.4% vs 0.9%). The incidence of
      surgical complications, respiratory, neurological and renal complications was not
      significantly different between groups, while the length of hospital stay was
      significantly higher in the group of patients with left dominance, p = 0.003.
      CONCLUSION: Left coronary dominance is an important risk factor for patients
      undergoing surgical myocardial revascularization.

PMID- 25870468
TI  - Performance of clinical signs in the diagnosis of dehydration in children with
      acute gastroenteritis.
AB  - BACKGROUND: Acute evaluation and treatment of children presenting with
      dehydration represent one of the most common situation in the pediatric emergency
      department. To identify dehydration in infants and children before treatment, a
      number of symptoms and clinical signs have been evaluated. The aim of the study
      was to describe the performance of clinical signs in detecting dehydration in
      children. METHODS: Two hundred children aged 1 month to 5 year were involved in
      our prospective study. The clinical assessment consisted of the ten clinical
      signs of dehydration, including those recommended by WHO (World Health
      Organization), heart rate, and capillary refill time. RESULTS: Two hundred
      patients with diarrhea were enrolled in the study. The mean age was 15.62+/-9.03
      months and 57.5% were male. Of these 121 had a fluid deficit of < 5%, 68 had a
      deficit of 5 to 9% and 11(5.5%) had a deficit of 10% or more. Patients classified
      as having no or mild, moderate, and severe dehydration were found to have the
      following respective gains in percent weight at the end of illness: 2.44+/-0.3,
      6.05+/- 1.01 and, 10.66+/- 0.28, respectively. All clinical signs were found more
      frequently with increasing amounts of dehydration(p<0.001, One-way ANOVA). The
      median number of findings among subjects with no or mild dehydration (deficit
      <5%) was 3; among those with moderate dehydration (deficit 5% to 9%) was 6.5 and
      among those with severe dehydration (deficit >10%) the median was 9 (p<0.0001,
      Kruskal-Wallis test). Using stepwise linear regression and a p value of <0.05 for
      entry into the model, a four-variable model including sunken eyes, skin
      elasticity, week radial pulse, and general appearance was derived. CONCLUSION:
      None of the 10 findings studied, is sufficiently accurate to be used in
      isolation. When considered together, sunken eyes, decreased skin turgor, weak
      pulse and general appearance provide the best explanatory power of the physical
      signs considered.

PMID- 25870469
TI  - Psoriasis and high blood pressure.
AB  - INTRODUCTION: Psoriasis is a chronic skin ailment which can be connected with an
      increased occurrence of other illnesses, including high blood pressure. EXAMINEES
      AND METHODS: A prospective study has been conducted which included 70 patients
      affected by psoriasis, both genders, older than 18 years. Average age being 47,14
      (SD= +/-15,41) years, from that there were 36 men or 51,43 and 34 women or
      48,57%. Average duration of psoriasis was 15,52 (SD=+/-12,54) years. RESULTS:
      Frequency of high blood pressure in those affected by psoriasis was 54,28%.
      Average age of the patients with psoriasis and high blood pressure was 53,79 year
      (SD=+/-14,15) and average duration of psoriasis was 17,19 years (SD=+/-13,51).
      Average values of PASI score were 16,65. Increase in values of PASI score and
      high blood pressure were statistically highly related (r=0,36, p=0,0001).
      CONCLUSION: Psoriasis was related to high blood pressure and there was a
      correlation between the severity of psoriasis and high blood pressure.

PMID- 25870470
TI  - Controversies in treatment of acetabular fracture.
AB  - INTRODUCTION: Acetabular fractures treatment represents a great controversy,
      challenge and dilemma for an orthopedic surgeon. AIM: The aim of the paper was to
      present the results of treatment of 96 acetabular fractures in the Clinic of
      Traumatology Banja Luka, in the period from 2003 to 2013, as well as to raise
      awareness regarding the controversy in the methods of choice in treating
      acetabulum fractures. MATERIAL AND METHODS: The series consists of 96 patients,
      82 males and 14 females, average age 40.5 years. Traffic trauma was the cause of
      fractures in 79 patients (85%), and in 17 patients (15%) fractures occurred due
      to falls from height. Polytrauma was present in 31 patients (32%). According to
      the classification of Judet and Letournel, representation of acetabular fractures
      was as follows: posterior wall in 32 patients, posterior column in 28, anterior
      wall in 4, anterior column in 2, transverse fractures in 8, posterior wall and
      posterior column in 10, anterior and posterior wall in 6, both- column in 4 and
      transversal fracture and posterior wall in 2 patients. 14 patients were treated
      with traction, that is, 6 patients with femoral traction and 8 patients with both
      lateral and femoral traction. 82 patients (86.4%) were surgically treated. Kocher
      Langenbeck approach was applied in the treatment of 78 patients. In two patients
      from the Kocher-Langenbeck's approach, the Ollier's approach had to be applied as
      well. Two acetabular were primarily treated with Ollier's approach. Extended
      Smith- Peterson's approach was applied 4 times, and Emile Letournel's
      (ilioinguinal) approach 14 times. RESULTS: Functional outcome (after follow-up of
      18 months), according to the Harris hip score of surgical treatment in 82
      patients, was as follows: good 46 (56%), satisfactory 32 (39%) and poor 4 (5%).
      Results of acetabulum fractures treated with traction were: good 8 (57%),
      satisfactory 4 (28%) and poor 2 (15%). According to the Brook's classification of
      heterotopic ossification, periarticular hetero-tropic calcifications after
      surgical treatment were: 0 degrees  in 65 patients (79%), I-II degrees  in 9
      patients (11%) and III-IV  degrees  in 8 patients (10%). Calcifications in 14
      patients treated with traction of heterotopic ossification by Brook-s
      classification were as follows: 0 degrees  in 10 patients (72%), I-II  degrees 
      in 3 patients (22%) and III-IV degrees  in 1 patient (6%). CONCLUSION: At the
      occurrence of acetabular fracture, it is necessary to start the treatment
      immediately, with an obligatory application of thromboembolic and antibiotic
      prophylaxis. Conservative treatment is acceptable if the dislocation of fracture
      is less than 5 mm. Indications for surgical treatment are incongruent or unstable
      fractures with verified dislocation greater than 5 mm, as well as when the
      radiography measured by JM Matta shows incongruence of acetabular roof less than
      40 degrees  in all planes. Kocher-Langenbeck approach is the choice of surgical
      approach for the management of posterior column / wall, and Letournel's
      (ilioinguinal) approach is the choice for the management of anterior wall/column.

PMID- 25870471
TI  - Isokinetic Testing in Evaluation Rehabilitation Outcome After ACL Reconstruction.
AB  - INTRODUCTION: Numerous rehab protocols have been used in rehabilitation after ACL
      reconstruction. Isokinetic testing is an objective way to evaluate dynamic
      stability of the knee joint that estimates the quality of rehabilitation outcome
      after ACL reconstruction. Our investigation goal was to show importance of
      isokinetic testing in evaluation thigh muscle strength in patients which
      underwent ACL reconstruction and rehabilitation protocol. SUBJECTS AND METHODS:
      In prospective study, we evaluated 40 subjects which were divided into two
      groups. Experimental group consisted of 20 recreational males which underwent ACL
      reconstruction with hamstring tendon and rehabilitation protocol 6 months before
      isokinetic testing. Control group (20 subjects) consisted of healthy recreational
      males. In all subjects knee muscle testing was performed on a Biodex System 4 Pro
      isokinetic dynamo-meter et velocities of 60 degrees /s and 180 degrees /s. We
      followed average peak torque to body weight (PT/BW) and classic H/Q ratio. In
      statistical analysis Student's T test was used. RESULTS: There were statistically
      significant differences between groups in all evaluated parameters except of the
      mean value of PT/BW of the quadriceps et velocity of 60 degrees /s (p>0.05).
      CONCLUSION: Isokinetic testing of dynamic stabilizers of the knee is need in
      diagnostic and treatment thigh muscle imbalance. We believe that isokinetic
      testing is an objective parameter for return to sport activities after ACL
      reconstruction.

PMID- 25870472
TI  - In vitro comparison of cytotoxicity of four root canal sealers on human gingival
      fibroblasts.
AB  - The goal of this in vitro study was to evaluate the relative biocompatibility of
      four endodontic sealers on the cell culture of the human fibroblast through
      cytotoxicity. MATERIALS AND METHODS: In this study four endodontics sealers was
      used GuttaFlow (Roeko)silicone based sealer, AH plus (De Tray-DENTSPLY) epoxy
      resin based, Apexit (Vivadent) calcium hydroxide based and Endorez (Ultradent)
      methacrylate based sealer. Sealers were tested on primary cell lines of human
      gingival fibroblasts. Experiments were preformed in laboratories of Hacettepe
      University of Ankara, Turkey and Faculty of Dentistry, University of Sarajevo,
      Bosnia and Herzegovina Cytotoxicity was determinate using WST-1 assay. RESULTS:
      Results were analyzed by SPSS 19 program. Kolgomorov-Smirnov test, Shapiro-Wilk
      and descriptive statistics also were used, as well as Kriskall-Wallis, ANOVA test
      and T- test. According to our results all four sealers showed different
      cytotoxicity effects on human gingival fibroblast cell culture, but all of them
      are slightly cytotoxic. CONCLUSIONS: According to results of this study it can be
      concluded: all four sealers showed different cytotoxicity effects on primary cell
      lines of human gingival fibroblasts, but all of them are slightly cytotoxicity.

PMID- 25870473
TI  - Low-dose Vitamin "A" Tablets-treatment of Acne Vulgaris.
AB  - BACKGROUND: The efficacy of isotretinoin at 0.5 to 1.0 mg/kg per day in the
      treatment of acne is well established and considered safe, although it is
      sometimes not easily tolerated because of its cutaneous side effects. OBJECTIVE:
      The purpose of this study was to determine the efficacy of low-dose isotretinoin
      in the treatment of acne. METHODS: In this prospective, non comparative, open
      label study, 50 patients, both male and female, with moderate acne were enrolled
      and treated with isotretinoin at 20 mg/d (approximately 0.3-0.4 mg/kg per day)
      for 3 months. The patients were divided into two age groups: 12 to 20 and 21 to
      35 years old. Patients were evaluated at 2-month intervals by means of clinical
      and laboratory examinations. A 4-year follow-up was also carried out. RESULTS: At
      the end of the treatment phase, good results were observed in 90.8% of the
      patients aged 12 to 20 years, and in 89.6% of the patients aged 21 to 35 years.
      Failure of the treatment occurred in 5.2% and 7.4% of the two groups,
      respectively. Three patients dropped out of the study because of lack of
      compliance, and another patient discontinued participation because of a
      laboratory side effect. During the 2-year follow-up period, relapses of the acne
      occurred in 3.9% of the patients aged 12 to 20 years and in 5.9% of the patients
      aged 21 to 35 years. Elevated serum lipid levels (up to 20% higher than the upper
      limit of normal value) were found in 4.2% of the patients and abnormal (<twice
      the upper limit of normal values) liver tests were observed in 4.8%. LIMITATIONS:
      This was a non comparative, open-label study. CONCLUSION: Three months of
      treatment with low-dose isotretinoin (20 mg/d) was found to be effective in the
      treatment of moderate acne, with a low incidence of severe side effects and at a
      lower cost than higher doses.

PMID- 25870474
TI  - Balneotherapy in treatment of spastic upper limb after stroke.
AB  - INTRODUCTION: After stroke, spasticity is often the main problem that prevents
      functional recovery. Pain occurs in up to 70% of patients during the first year
      post-stroke. MATERIALS AND METHODS: A total of 70 patients (30 female and 45
      male) mean age (65.67) participated in prospective, controlled study. INCLUSION
      CRITERIA: ischaemic stroke, developed spasticity of upper limb, post-stroke
      interval <6 months. EXCLUSION CRITERIA: contraindications for balneotherapy and
      inability to follow commands. Experimental group (Ex) (n=35) was treated with
      sulphurous baths (31 degrees -33 degrees C) and controlled group (Co) with taped
      water baths, during 21 days. All patients were additionally treated with
      kinesitherapy and cryotherapy. The outcome was evaluated using Modified Ashworth
      scale for spasticity and VAS scale for pain. The significance value was sat at
      p<0.05. GOAL: To find out the effects of balneotherapy with sulphurous bath on
      spasticity and pain in affected upper limb. RESULTS: Reduction in tone of
      affected upper limb muscles was significant in Ex group (p<0.05). Pain decreased
      significantly in Ex-group (p<0.01). CONCLUSION: Our results show that
      balneotherapy with sulphurous water reduces spasticity and pain significantly and
      can help in treatment of post-stroke patients.

PMID- 25870475
TI  - Analysis of the influence of type of diabetes mellitus on the development and
      type of glaucoma.
AB  - AIM: Main the goal of the research is to analyze the occurrence of glaucoma in
      patients with diabetes mellitus type 1 (DM type 1) and diabetes mellitus type 2
      (DM type 2). PATIENTS AND METHODS: The study involved 140 patients, 34 with DM
      type 1 and 106 with DM type2. In relation to the type of glaucoma to the patients
      are divided into two groups: Primary and Secondary glaucoma. According to the
      stage of diabetic retinopathy (DR) patients were analyzed in three groups: non
      proliferative, preproliferative and proliferative DR. Since ophthalmological
      parameters were analyzed: best corrected visual acuity (BCVA), intraocular
      pressure (IOP), visual field (VF) of computerized perimetry, excavatio optic
      nerve (E/D) by optic coherent tomography (OCT). RESULTS: Applying the test of
      quotient chance found that subjects with DM type 1 have a 5.94 times greater
      chance of developing secondary glaucoma, but is of primary (P <0.0001). In
      patients with DM type 2, where the chance of getting the subjects of secondary
      glaucoma 4.43 times larger than that of the primary (P = 0.0002). CONCLUSION:
      Patients with DM type have great chance of developing secondary glaucoma of the
      primary. Primary glaucoma more common in NPDR but secondary glaucoma more common
      in PDR.

PMID- 25870476
TI  - Grandmultiparity: risk factors and outcome in a tertiary hospital: a comparative
      study.
AB  - AIMS: The aim of the current study was to determine the prevalence of
      grandmultiparity and the associated risks factors. METHODS: Four hundred thirty
      grandmutliparas (parity 5 or more) were compared with multiparous population
      (parity 2-4) with regard to maternal age, gestational age, mode of delivery,
      fetal and maternal outcomes and inter-current medical and obstetrical problems.
      RESULTS: There were significant association between grandmultiparity and adverse
      pregnancy outcomes such as cesarean delivery (OR=2.699, CI=2.072-3.515, p<0.001),
      fetal macrosomia (OR=1.675; 95% CI=1.004- 2.796, p=.048), Diabetes mellitus
      (OR=1.634, 95%CI=1.076-2.481, p=0.021), and pregnancy induced hypertension
      (OR=1.838, 95% CI=1.054-3.204, p=.032). No significant associations were seen in
      placenta abruption, placenta previa, preterm labor, postpartum hemorrhage and the
      frequency of admission to neonatal intensive care unit. No prenatal or maternal
      mortality was reported in this study. CONCLUSION: Grandmultiparty remains a major
      obstetrics problem. It is associated with many medical and obstetrical
      complications. In communities where large family is desirable it is important to
      address the value of family planning and conduction of meticulous antenatal care.

PMID- 25870477
TI  - Modes of presentation of reactive arthritis based on the affected joints.
AB  - INTRODUCTION: Reactive arthritis is an autoimmune condition that occurs as a
      reaction against an infection site elsewhere in the body. Reactive arthritis
      affects mostly young ages, mainly group age 20-40 y.o., mostly males with ratio
      2:1 against females, sometimes 3:1, and even 14:1. The purpose of the study was
      to observe the mode of illness presentation based on the number of affected
      joints. MATERIAL AND METHODS: During the 01.03.2012 - 01.03.2014 in the Clinic
      for Rheumatology and O.S.I.R. "Vendenisi - AL" in Besiana have been examined,
      elaborated and hospitalized 100 patients with reactive arthritis, out of them 66
      males and 34 females. Patients underwent necessary laboratory, hematological,
      biochemical, and immunological examinations. Subsequently each affected joint has
      been examined based on the propedeutics rules (inspection, palpation and
      assessment of the level of motility), as well as x ray examination. RESULTS: From
      100 examined patients 66% were males and 34% females respectively. 11% of them
      were in the 10-20y.o. group age, 30% belonged to group age 21-30 y.o., 24% of
      patients to 31-40 y.o. group age, 30% to 41-50 y.o. group age, and 5% of patients
      to the group age over the 51 year old. Regarding the affected articulations and
      modes of illness presentation, we've obtained the following results: Knee was
      affected in 64.7% female and 52,12% male patients respectively, T/C joint in 50%
      female and 57.57% male patients, MTPH joint in 41.11% female and 48.48% male
      patients respectively, and R/C joint in 44.11% female and 48.48% male patients
      respectively. Oligoarticular type is seen in 73% male and 70% female patients.
      Monoarticular type is seen in 14% male and 13% female patients, and poliarticular
      type is seen in 10% male and 14% female patients respectively. Results from our
      study have revealed that: reactive arthritis is more frequent in males than
      females in ratio 2:1 in the infections of urogenital infection, 3:1 in
      nasopharyngeal infections, and similar in infections of enteral origin.
      CONCLUSION: Reactive arthritis mostly attacks young ages 20-40 y.o., while over
      the age of 50 and below the age of 20 is rarely seen. First reactive arthritis
      attack in males occurs earlier than in females. Most affected joints are: knee,
      talocrural joint, metatarsophalangeal (MTPH) joint, radiocarpal (R/C) joint, and
      proximal interphalanteal (PIPH) joint. Oligoarticular mode of illness
      presentation is 2.5 more frequent than mono and poliarticular mode of illness
      presentation.

PMID- 25870478
TI  - Insulin resistance in early vs late nutrition and complications of sirs in
      neurosurgical intensive care unit (ICU).
AB  - BACKGROUND: Systemic Inflammatory Response Syndrome (SIRS) is a common
      complication in neurosurgical diseases in Intensive Care Unit (ICU). Because of
      associated insulin resistance (IR) the ICU is in dilemma in which stage to start
      the nutrition to patients and what is the amount of Insulin Unit to control the
      hyperglycemia. AIM: to define the IR and to compare IR and amount of insulin
      among ICU patients in "Mother Theresa" University Hospital Center (MTUHC) in
      Tirana Albania. METHODS: 154 patients with neurosurgical disease and SIRS
      complications were randomized in two groups: early nutrition 73 patients (47%)
      and late nutrition 81 (53%) and compared for a number of variables. RESULTS:
      There was no statistical age and gender difference between the two groups
      (P>0.05). The amount of insulin units to control the level of glycemia (80-110
      mg/dc) was 12.8+/-7 unit per day in early nutrition and 23.8 +/-12.9 units in
      late nutrition group (p<0.01). No patient in early nutrition group but six (7.4%)
      patients in late nutrition group developed insulin resistance (p=0.03).
      CONCLUSIONS: the IR due to the infection complications is higher among late than
      early nutrition group. Therefore, we suggest that in neurosurgical ICU it would
      be better to start the nutrition within 72 hours.

PMID- 25870479
TI  - Heart lesion after the first attack of the rheumatic Fever 22 years experience in
      single centre.
AB  - BACKGROUND: Acute rheumatic fever and its sequels, rheumatic heart diseases,
      remain major unsolved preventable health problems in Kosovo population,
      particularly among the disadvantages indigenous Albanian and Egyptians people. In
      Kosovo, despite of performing secondary prophylaxis with benzathine penicillin,
      acute rheumatic fever hospitalization rates have remained essentially unchanged
      for the last 20 years. The role of echocardiography in the diagnosis of acute
      rheumatic carditis was established over the last 20 years. AIMS: In this study we
      aimed to determine the prevalence of rheumatic heart disease in children from
      Kosovo population with first attack of acute rheumatic fever. Also, we presented
      that echocardiography examination detects a greater prevalence of rheumatic heart
      disease than other diagnostic procedures. We aimed to compare the sensitivity and
      specificity of cardiac auscultation, ECG record, lab analysis to echocardiography
      and to determine the feasibility of specific age in this setting. METHODS: To
      optimize accurate diagnosis of rheumatic fever and rheumatic heart disease, we
      utilized two group models. In the first group of 388 children, hospitalized and
      treated before 1999, diagnosis of rheumatic fever was decided basing on the
      clinical and laboratory findings whereas in second group (221 children treated
      from1999 to 2010) clinical and lab diagnosis were amplified also on the detection
      by echocardiography. CONCLUSION: In second group, using echocardiography as a
      method of diagnosis and assessment children with rheumatic fever, we found high
      rates of undetected rheumatic heart disease in this high-risk group population.
      Echocardiographic examination of children with rheumatic fever for rheumatic
      heart disease may over diagnose rheumatic heart disease unless congenital mitral
      valve anomalies and physiological regurgitation are excluded.

PMID- 25870480
TI  - Operative treatment of combined aortic stenosis and coronary artery disease.
AB  - INTRODUCTION: The aortic valve replacement is a standard operating procedure in
      patients with severe aortic stenosis. Structure of patients undergoing surgery
      ranges from young population with isolated mitral valvular disease to the elderly
      population, which is in addition to the underlying disease additionally burdened
      with comorbidity. One of the most commonly present factors that further
      complicate the surgery is coronary heart disease that occurs in, almost, one
      third of patients with aortic stenosis. The aim is to compare the results of
      surgery for aortic valve replacement with or without coronary artery bypass graft
      (CABG). PATIENTS AND METHODS: From August 2008 to January 2013 in our center
      operated on 120 patients for aortic stenosis. Of this number, 75 were men and 45
      women. The average age was 63.37 years (16-78). Isolated aortic valve replacement
      was performed in 89 patients and in 31 patients underwent aortic valve
      replacement and coronary bypass surgery. Implanted 89 biological and 31
      mechanical valves. RESULTS: Patients with associated aortic stenosis and coronary
      artery disease were more expressed symptomatic symptoms preoperatively to
      patients with isolated aortic stenosis who were on average younger age. Intra
      hospital morbidity and mortality was more pronounced in the group of patients
      with concomitant aortic valve replacement and coronary bypass surgery. Morbidity
      was recorded in 17 patients (14.3%) in both groups, while the mortality rate in
      both groups was 12 patients (10.1%). CONCLUSION: Evaluation of preoperative risk
      factors and comorbidity in patients with aortic stenosis and coronary artery
      disease contributes to a significant reduction in intraoperative and
      postoperative complications. Also, early diagnosis of associated coronary artery
      disease and aortic stenosis contributes to timely decision for surgery thus
      avoiding subsequent ischaemic changes and myocardial damage.

PMID- 25870481
TI  - Dermatomycosis frequency and localization sites.
AB  - INTRODUCTION: Since the prevalence of skin mycotic infections is changing and is
      area depended we aimed to analyze the frequency of the skin myocotic infections
      and the appearance sites. MATERIAL AND METHODS: There were involved 560 patients
      referred to the Dermatology Clinic of University Clinical Center of Kosova during
      a period of one year. RESULTS: The mean age of our study group was around
      thirties with a predominance of female and rural patients. Although most of cases
      presented with single site disease localization, we observed the increase in
      number of cases with more than one site localization with age. CONCLUSION: The
      increased prevalence skin mycotic infections, as well as more than one place of
      localization deserve a multidimensional approach.

PMID- 25870482
TI  - Does melissa officinalis cause withdrawal or dependence?
AB  - INTRODUCTION: Melissa officinalis is a medical and aromatic plant that is used
      for its hypnotic, sedative, and spasmolytic effects. This report presents a case
      study of30-year-old patient who was admitted to an emergency department with
      restlessness, tremor, distractibility, and sweating following a discontinuation
      of Melissa officinalis consumption. CASE REPORT: In this case, withdrawal
      symptoms may be related to the dependence effect caused by long-term use of
      Melissa officinalis. Although Melissa officinalis, a plant, is preferred by many
      patients as an alternative to pharmaceutical drugs, patients should be made aware
      that it may have a risk of dependency and can lead to withdrawal symptoms.

PMID- 25870484
TI  - Meta-analysis as Statistical and Analytical Method of Journal's Content
      Scientific Evaluation.
AB  - INTRODUCTION: A meta-analysis is a statistical and analytical method which
      combines and synthesizes different independent studies and integrates their
      results into one common result. GOAL: Analysis of the journals "Medical
      Archives", "Materia Socio Medica" and "Acta Informatica Medica", which are
      located in the most eminent indexed databases of the biomedical milieu. MATERIAL
      AND METHODS: The study has retrospective and descriptive character, and included
      the period of the calendar year 2014. Study included six editions of all three
      journals (total of 18 journals). RESULTS: In this period was published a total of
      291 articles (in the "Medical Archives" 110, "Materia Socio Medica" 97, and in
      "Acta Informatica Medica" 84). The largest number of articles was original
      articles. Small numbers have been published as professional, review articles and
      case reports. Clinical events were most common in the first two journals, while
      in the journal "Acta Informatica Medica" belonged to the field of medical
      informatics, as part of pre-clinical medical disciplines. Articles are usually
      required period of fifty to fifty nine days for review. Articles were received
      from four continents, mostly from Europe. The authors are most often from the
      territory of Bosnia and Herzegovina, then Iran, Kosovo and Macedonia. CONCLUSION:
      The number of articles published each year is increasing, with greater
      participation of authors from different continents and abroad. Clinical medical
      disciplines are the most common, with the broader spectrum of topics and with a
      growing number of original articles. Greater support of the wider scientific
      community is needed for further development of all three of the aforementioned
      journals.

PMID- 25870483
TI  - Acute Respiratory Distress Syndrome (ARDS) from Endemic Influenza A/H1N1:
      Prehospital Management.
AB  - Acute respiratory distress syndrome (ARDS) is a form of acute life threatening
      respiratory failure. In daily practice there is difficulty in diagnostic and
      therapeutic management of Acute respiratory distress syndrome (ARDS). We observed
      delay in diagnostic and therapeutic procedures in patients with clinical signs
      for the presence of severe respiratory disorders. Finding timely evidence of the
      presence the clinical signs of threatening ARDS and underlying diseases like
      influenza A/H1N1 during prehospital period in early stage of disease it is
      possible introduce early adequate treatment: high flow oxygen, fluid replacement
      and pharmacological and antiviral therapy. This measure can reduce high mortality
      in patients who develop ARDS. It is important to improve diagnostic criteria for
      a precise definition of ARDS and transfer it in practice of emergency and family
      medicine, microbiology, intensive care units, hospital departments of infectious
      and respiratory diseases. In this article we underlined the key elements of the
      new definition of ARDS, diagnostic criteria and the importance of early diagnosis
      in prehospital period following clinical feature and course (a presence of severe
      dyspnea) by adding chest x-ray and laboratory investigations. 

PMID- 25870485
TI  - Physiological cost index and comfort walking speed in two level lower limb
      amputees having no vascular disease.
AB  - BACKGROUND: The Physiological Cost Index (PCI) was introduced by MacGregor to
      estimate the energy cost in walking of healthy people, also it has been reported
      for persons with lower limb amputation, walking with prosthesis. OBJECTIVE: To
      assess energy cost and walking speed in two level lower limb amputation:
      transfemoral and transtibial amputation and to determine if the age and
      prosthetic walking supported with walking aids have impact on energy cost and
      walking speed. METHODS: A prospective cross sectional study was performed in two
      level lower limb amputees with no vascular disease who were rehabilitated at the
      Department of Prosthetics and Orthotics at the University Clinical Center of
      Kosovo. The Physiological Cost Index (PCI) was assessed by five minutes of
      continuous indoor walking at Comfort Walking Speed (CWS). RESULTS: Eighty three
      lower limb amputees were recruited. It is shown relevant impact of level of
      amputation in PCI (t=6.8, p<0.001) and CWS (T=487, p<0.001). The great influence
      of using crutches during prosthetic walking in PCI (ANOVA F= 39.5 P < 0.001) and
      CWS (ANOVA F=32.01, P <0.001) has been shown by One Way ANOVA test. The
      correlation coefficient (R) showed a significant correlation of age with PCI and
      CWS in both groups of amputation. CONCLUSIONS: Walking with transfemoral
      prosthesis or using walking aids during prosthetic ambulation is matched with
      higher cost of energy and slower walking speed. Advanced age was shown with high
      impact on PCI and CWS in both groups of amputees.

PMID- 25870486
TI  - Minimum data set for cystic fibrosis registry: a case study in iran.
AB  - BACKGROUND: over the last 25 years several national registries of CF have been
      set up. Such systems can be very useful in providing an integrated resource for
      improving patient care and conducting research on the disease. Minimum Data Set
      is a common set of data items that should be used to collect and report data in
      the registry. The principal aim of this research was to determine minimum data
      set for the CF registry in north-west of Iran. METHODS: data items collected by
      several selected registries of cystic fibrosis were studied and an initial set of
      data was selected by the researchers. A group of experts including
      epidemiologists, pediatricians, and CF specialists were asked to review the
      proposed data elements and score them based on their importance by using a nine
      point Likert scale. The items scored as important or highly important by more
      than 50 % of the experts, were included in final list of minimum data set.
      Availability of data was evaluated through reviewing medical records of 144
      patients hospitalized in Children Hospital located in Tabriz. RESULTS: overall
      six classes of data (46 items) were identified in the selected registry systems
      for cystic fibrosis: patient demographics, administrative data, survival status,
      diagnostic procedures, genetic and clinical manifestations, and therapeutics.
      Thirty two data elements from all six categories of data were approved by the
      experts as the minimum data set for cystic fibrosis registry system. Availability
      of data in administrative category and survival class was 100 percent. Collecting
      data on medications was feasible in 100% of the cases as well. In class of
      demographic data, accessibility of patient name, age, gender, place of birth, and
      date of birth was 100 percent. In group of diagnostic procedures, partial
      availability of data was found for sweat test and genetic test. No data was found
      on the antenatal screening, exercise tolerance test, and glucose tolerance test.
      CONCLUSION: this work can be considered as a first step toward establishing CF
      registry system in Iran. Minimum data set can be also useful in designing
      electronic registry or electronic patient records for those suffering from CF
      toward integration of their fragmented records across continuum of the health
      care system in order to improve quality of shared patient care.

PMID- 25870487
TI  - Work-related Mental Consequences: Implications of Burnout on Mental Health Status
      Among Health Care Providers.
AB  - INTRODUCTION: Burnout can create problems in every aspect of individual's' human
      life. It may have an adverse effect on interpersonal and family relations and can
      lead to a general negative attitude towards life. AIM: The purpose of this study
      is to investigate whether burnout is associated with the mental health status of
      health care providers. MATERIAL AND METHODS: The sample in this study consisted
      of 240 health care employees. The Greek version of Maslach's Burnout Inventory
      (MBI) was used for measuring burnout levels and the Greek version of the Symptoms
      Rating Scale for Depression and Anxiety (SRSDA) questionnaire was used to
      evaluate health care providers' mental health status. Descriptive statistics were
      initially generated for sample characteristics. Normality was checked by the
      Kolmogorov-Smirnov test and data was processed with parametric tests. General
      linear models with MBI dimensions as independent variables and SRSDA subscales as
      dependent variables were used to determine the relation between burnout and
      mental health status. Statistics were processed with SPSS v. 17.0 (SPSS, Chicago,
      IL, USA). Statistical significance was set at p=0.05. RESULTS: The average age of
      the sample is 40.00+/-7.95 years. Regarding gender the percentage of men is
      21.40% (N=49) and of women is 78.60% (N=180). Overall the professional burnout of
      health care workers is moderate. The mean score for emotional exhaustion is
      26.41, for personal accomplishment 36.70 and for depersonalization 9.81. The mean
      for each subscale of SRSDA is 8.23+/-6.79 for Depression Beck-21, 3.96+/-4.26 for
      Depression Beck-13, 4.91+/-4.44 for Melancholia, 6.32+/-4.35 for Asthenia and
      6.36+/-4.72 for Anxiety. The results of general linear models with the MBI
      dimensions as independent variables and the SRSDA subscales as dependent
      variables are shown that emotional exhaustion and personal accomplishment are
      statistically correlated with all subscales of SRSDA, while depersonalization is
      not correlated with any SRSDA subscale. CONCLUSIONS: Burnout appears to implicate
      mental health status of healthcare providers in work index. Emotional exhaustion
      is the burnout dimension that is correlated the most with employees' mental
      health.

PMID- 25870488
TI  - The effect of applying podcast multimedia teaching system on motivational
      achievement and learning among the boy students.
AB  - BACKGROUND: Traditional education classes are no more effective because they are
      tied to a particular place and time. Podcast complete the defection of other
      educational resources. In this study we aimed to address whether utilizing
      podcast multimedia training system has an effect on the motivational achievement
      and students learning of the Arabic course in high school. METHODS: In this
      practical-purposed, descriptive and quasi-experimental study, pre- and post-test
      method in control and experiment groups was used. Researchers used simple random
      sampling method to form the groups. RESULTS: The results showed the normal
      distribution of data according to the value of z (0.09) in the pre- and post
      tests in both control and experiment groups. Therefore, the data distribution was
      normal (P>0.925). Significant differences between experimental and control groups
      in terms of academic level were not observed in the pre-test. There was no
      significant difference between the motivational achievement of education in post
      test of control and experiment group (p>0.89). CONCLUSION: The results showed
      that teaching with podcast multimedia systems significantly increased learning of
      Arabic in the high school level. But of motivation reinforcement between
      traditional method and system for multimedia podcasts, showed no significant
      differences. Each variety of multimedia techniques can be beneficial for a
      specific course. Therefore, more studies on the effectiveness of podcast method
      in different courses to determine its effects are necessary.

PMID- 25870489
TI  - The relationship between perceived stress and computer technology attitude: an
      application on health sciences students.
AB  - INTRODUCTION: The aim of this study is to define attitudes of students in health
      sciences towards perceived personal stress and computer technologies, and to
      present the relationship between stress and computer technology attitudes.
      METHODS: In this scope, this study has a descriptive nature and thus a
      questionnaire has been applied on 764 students from Afyon Kocatepe University
      Health Sciences High School, Turkey for data gathering. Descriptive statistics,
      independent samples, t test, one way ANOVA, and regression analysis have been
      used for data analysis. FINDINGS: In the study, it is seen that female (=3,78)
      have a more positive attitude towards computer technology than male students
      (=3,62). according to the results of regression analysis of the study, the
      regression model between computer technology attitude (CTA) and perceived stress
      (PS) has been found meaningful (F=16,291; p<0,005). There was a negative
      relationship between computer technology attitude and perceived stress (when
      computer technology altitude increases, perceived stress decreases), and an
      increase of one unit in computer attitude results in 0.275 decrease in perceived
      stress. CONCLUSIONS: it can be concluded that correct and proper use of computer
      technologies can be accepted as a component of overcoming stress methods.

PMID- 25870490
TI  - Managing the security of nursing data in the electronic health record.
AB  - BACKGROUND: The Electronic Health Record (EHR) is a patient care information
      resource for clinicians and nursing documentation is an essential part of
      comprehensive patient care. Ensuring privacy and the security of health
      information is a key component to building the trust required to realize the
      potential benefits of electronic health information exchange. This study was
      aimed to manage nursing data security in the EHR and also discover the viewpoints
      of hospital information system vendors (computer companies) and hospital
      information technology specialists about nursing data security. METHODS: This
      research is a cross sectional analytic-descriptive study. The study populations
      were IT experts at the academic hospitals and computer companies of Tehran city
      in Iran. Data was collected by a self-developed questionnaire whose validity and
      reliability were confirmed using the experts' opinions and Cronbach's alpha
      coefficient respectively. Data was analyzed through Spss Version 18 and by
      descriptive and analytic statistics. RESULTS: The findings of the study revealed
      that user name and password were the most important methods to authenticate the
      nurses, with mean percent of 95% and 80%, respectively, and also the most
      significant level of information security protection were assigned to
      administrative and logical controls. There was no significant difference between
      opinions of both groups studied about the levels of information security
      protection and security requirements (p>0.05). Moreover the access to servers by
      authorized people, periodic security update, and the application of
      authentication and authorization were defined as the most basic security
      requirements from the viewpoint of more than 88 percent of recently-mentioned
      participants. CONCLUSIONS: Computer companies as system designers and hospitals
      information technology specialists as systems users and stakeholders present many
      important views about security requirements for EHR systems and nursing
      electronic documentation systems. Prioritizing of these requirements helps policy
      makers to decide what to do when planning for EHR implementation. Therefore, to
      make appropriate security decisions and to achieve the expected level of
      protection of the electronic nursing information, it is suggested to consider the
      priorities of both groups of experts about security principles and also discuss
      the issues seem to be different between two groups of participants in the
      research.

PMID- 25870491
TI  - An assessment of sexual dimorphism in relation to facial asymmetry in
      esthetically pleasing faces.
AB  - OBJECTIVE: The aim of the study is to detect gender-wise difference in the
      skeletal asymmetry in the esthetically pleasing faces. MATERIALS AND METHODS: a
      cross sectional study was conducted on 25 females and 25 males of age 18 -25
      years using the posterior-anterior cephalograms. The selected part of grummon's
      frontal analysis for analyzing the vertical skeletal asymmetries, mandibular
      morphology, transverse asymmetry and mandibular deviation was used. The obtained
      data was subjected to independent student's't' test for comparing the difference
      between males and females. RESULTS: there was statistically significant
      difference between the males and females for the measurements like Gonion-Menton
      length for the mandibular morphology and for the transverse parameters like
      zygomatico frontal suture length, jular length and antegonial notch length. There
      was no significant difference for the sidedness of asymmetry for the males and
      females. CONCLUSION: frontal facial asymmetry showed sexual dimorphism with males
      showing greater asymmetric values than the females. The asymmetry showed right
      sided prominence for both the males and females. This knowledge can be utilized
      for planning facial reconstruction and remodeling surgeries.

PMID- 25870492
TI  - Importance of dental records in forensic dental identification.
AB  - INTRODUCTION: The patient's record maintains all the diagnostic information with
      regards to patients and contains valuable information that can be beneficial to
      the dentist as well as legal authorities during forensic human identification.
      AIM: Objective of the study was to compare dental records with an ideal dental
      record form, as well as to compare between dental records of private clinics and
      academic hospitals and to assess the awareness and the knowledge of the dentists
      regarding the maintenance of their dental records accurate for medico-legal
      purposes. MATERIAL AND METHODS: A comparative cross-sectional study between
      records kept in private clinics and academic teaching hospitals in Khartoum
      locality. RESULTS: Our results showed that Students are more likely to encounter
      accurate dental records more than dentists in private clinics. In conclusion
      Students are more aware regarding medicolegal purposes of maintenance of dental
      records. Accurate maintenance of dental records is more among dental students.
      Therefore, private clinics encounter dental records as financial documents.

PMID- 25870493
TI  - Predictors of patients' satisfaction with health care services in three balkan
      countries (macedonia, bulgaria and serbia): a cross country survey.
AB  - BACKGROUND: Patients' satisfaction with provided healthcare services is one of
      the factors to measure the overall quality of the delivered health care. Main
      objective of our study was to determine the common predictors associated with
      patients 'satisfaction in three Balkan countries. METHODS: We conducted web based
      survey among population in Macedonia, Serbia and Bulgaria using paid campaign
      over the social network Facebook. A questionnaire consisted of 31 questions was
      developed following studies on patients' satisfaction conducted elsewhere.
      Descriptive analysis was performed to assess the predictors associated with
      patients' satisfaction. In addition we performed content analysis to all open
      ended responses. RESULTS AND DISCUSSION: In total 4118 respondents participated
      in the survey. Main predictors associated with low users satisfaction with the
      health care services in three surveyed countries are waiting time to
      appointments, huge administrative procedures, and attitudes of the medical
      personnel towards the patients. The analysis showed that there are many
      similarities in user experiences in three countries, but also there are some
      differences. CONCLUSIONS: The health care systems in these three counties are
      organized around centralized and monopolistic position of one health insurance
      fund that serves as main purchaser of health care services. Top three indicators
      of patients' satisfaction across three countries are trust and overall
      satisfaction with the attention of the doctors, as well as satisfaction with the
      outcome of the treatment. Long waiting time and huge administrative procedures
      are determined as common predictor for lower patients' satisfaction across these
      Balkan countries. Patients' privacy protection is issue for concern in all three
      countries.

PMID- 25870494
TI  - Value Innovation in Hospital: Increase Organizational IQ by Managing Intellectual
      Capitals.
AB  - Hospital is a complex organization rich in intellectual capitals. Effective
      management of these assets in line with innovating value to reach strategic goals
      and objectives can lead to increasing organizational IQ. In hospital with high
      organizational IQ, Increasing syntropy in intellectual capitals can convert it to
      an agile, learner, innovative, and smart organization. 

PMID- 25870495
TI  - Early prenatal diagnosis of thoracopagus twins by ultrasound.
AB  - INTRODUCTION: Conjoined twins are identical twins joined in utero. It's a rare
      phenomenon and present a unique challenge to obstetricians and pediatric
      surgeons. Conjoined twins are complex complication of monozygotic twinning, which
      is associated with high perinatal mortality. CASE REPORT: At our clinic complete
      anomaly scan was done, the patients was found to have monozygotic twins of 15
      weeks gestation and carrying a conjoint twin. Our ultrasound revealed fully
      developed heads facing each other, joint at the thorax and sharing a common
      abdomen. These twins share a single heart with two atrium and two ventricle. They
      decide for termination of pregnancy after taken the opinion of religious people.
      Termination of pregnancy was performed by many methods and we chose to use
      cytotec tablets which inserted vaginally and the outcome was conjoint twin with
      two bodies fused from the upper thorax to lower belly. Both fetuses are female
      and died immediately after termination of pregnancy.

PMID- 25870496
TI  - The most influential scientists in the development of medical informatics (4):
      allan cormack.

PMID- 25870497
TI  - The acoustic salience of prosody trumps infants' acquired knowledge of language
      specific prosodic patterns.
AB  - There is mounting evidence that prosody facilitates grouping the speech stream
      into syntactically-relevant units (e.g., Hawthorne & Gerken, 2014; Soderstrom,
      Kemler Nelson, & Jusczyk, 2005). We ask whether prosody's role in syntax
      acquisition relates to its general acoustic salience or to the learner's acquired
      knowledge of correlations between prosody and syntax in her native language.
      English- and Japanese-acquiring 19-month-olds listened to sentences from an
      artificial grammar with non-native prosody (Japanese or English, respectively),
      then were tested on their ability to recognize prosodically-marked constituents
      when the constituents had moved to a new position in the sentence. Both groups
      were able to use non-native prosody to parse speech into cohesive, reorderable,
      syntactic constituent-like units. Comparison with Hawthorne & Gerken (2014), in
      which English-acquiring infants were tested on sentences with English prosody,
      suggests that 19-month-olds are equally adept at using native and non-native
      prosody for at least some types of learning tasks and, therefore, that prosody is
      useful in early syntactic segmentation because of its acoustic salience.

PMID- 25870498
TI  - Sketching Awareness: A Participatory Study to Elicit Designs for Supporting Ad
      Hoc Emergency Medical Teamwork.
AB  - Prior CSCW research on awareness in clinical settings has mostly focused on
      higher-level team coordination spanning across longer-term trajectories at the
      department and inter-department levels. In this paper, we offer a perspective on
      what awareness means within the context of an ad hoc, time- and safety-critical
      medical setting by looking at teams treating severely ill patients with urgent
      needs. We report findings from four participatory design workshops conducted with
      emergency medicine clinicians at two regional emergency departments. Workshops
      were developed to elicit design ideas for information displays that support
      awareness in emergency medical situations. Through analysis of discussions and
      clinicians' sketches of information displays, we identified five features of
      teamwork that can be used as a foundation for supporting awareness from the
      perspective of clinicians. Based on these findings, we contribute rich
      descriptions of four facets of awareness that teams manage during emergency
      medical situations: team member awareness, elapsed time awareness, teamwork
      oriented and patient-driven task awareness, and overall progress awareness. We
      then discuss these four awareness types in relation to awareness facets found in
      the CSCW literature.

PMID- 25870499
TI  - Noncompaction cardiomyopathy: A new mechanism for mitral regurgitation with
      distinct clinical, echocardiographic features and pathological correlations.
AB  - Noncompaction cardiomyopathy (NCCM) is a primary, genetic cardiomyopathy with
      variable clinical manifestations that include mitral regurgitation (MR). METHODS:
      This study comprised patients diagnosed with NCCM and MR in two cardiac centers
      (King Abdul-Aziz Cardiac Center, Riyadh, Kingdom of Saudi Arabia and Sudan Heart
      Institute, Khartoum, Sudan), and seen in the period between 2002 and 2013. The
      study describes follow up, clinical, echocardiographic, and histopathological
      findings. RESULTS: Nineteen cases (85% females) were identified. Ten percent of
      the cases had relapses and remissions of heart failure. Echocardiographic
      features included leaflet retraction in all patients, characteristic
      malcoaptation, and a zigzag deformity of anterior leaflet in 57% of patients.
      Ruptured chordae were found in 15% of the patients. One patient had pathological
      examination of the mitral valve which showed myxomatous degeneration, and
      sclerotic and calcific changes. CONCLUSION: We describe and discuss a new
      mechanism for MR caused by NCCM with identifiable clinical and echocardiographic
      features, and pathological correlations.

PMID- 25870500
TI  - Relationship between epistaxis and hypertension: A cause and effect or
      coincidence?
AB  - INTRODUCTION: Epistaxis is the most common otorhinolaryngological emergency.
      Whether there is an association or cause and effect relationship between
      epistaxis and hypertension is a subject of longstanding controversy. OBJECTIVE:
      The aim of our study is to evaluate the relationship between epistaxis and
      hypertension. MATERIALS AND METHODS: This study was conducted at Olaya Medical
      Center (Riyadh) during the period between May 2013 and June 2014. A total of 80
      patients were divided into two groups: Group A consisted of 40 patients who
      presented with epistaxis, and Group B consisted of 40 patients who served as a
      control group. Twenty-four-hour ambulatory blood pressure monitoring (ABPM) was
      performed for all patients. Patients were followed up for a period of three
      months. RESULTS: Readings of blood pressure (BP) were similar between the two
      groups regarding BP at presentation, ABPM, and BP at three months. There was a
      higher number of attacks in patients with history of hypertension. There was
      highly significant positive correlation between number of attacks of epistaxis
      and BP readings. Systolic BP at presentation was higher in patients who needed
      more complex interventions such as pack, balloon or cautery than those managed by
      first aid. CONCLUSION: We found no definite association between epistaxis and
      hypertension. Epistaxis was not initiated by high BP but was more difficult to
      control in hypertensive patients.

PMID- 25870501
TI  - Prognosis of primary percutaneous coronary intervention in elderly patients with
      ST-elevation myocardial infarction.
AB  - OBJECTIVE: To evaluate the prognosis of primary percutaneous coronary
      intervention (PPCI) and medical therapy (MT) in elderly patients presenting with
      ST-elevation myocardial infarction (STEMI). METHODS: A total of 238 STEMI
      patients aged above 80 and treated with PPCI (n = 186) and MT (n = 52) at
      Harefield Hospital, London were included in this study. Patients who did not have
      true STEMI based on non-diagnostic electrocardiogram (ECG) for STEMI and negative
      troponin, who presented with left bundle branch block (LBBB) and had normal
      coronaries were excluded from this study. Primary PCI was defined as any use of a
      guidewire for more than diagnostic purposes in patients with STEMI, whereas
      conventional MT was defined as treatment of patients with anti-platelets and anti
      thrombotic medications without thrombolysis. RESULTS: The survival rate of PPCI
      patients was 86% (n = 160) at month 1 followed by 83.9% (n = 156) at month 6, and
      81.2% (n = 151) at month 12. The survival rate of MT patients was 44.2% (n = 23)
      at month 1 followed by 36.5% (n = 19) at month 6, and 34.6% (n = 18) at month 12.
      Compared to MT, significantly fewer comorbidities were found in the PPCI group.
      Ventricular fibrillation (VF) (4.8%) and consequent admission to intensive care
      unit (7%) were the major complications of the PPCI group. CONCLUSION: PPCI has a
      higher survival rate and, compared to MT, fewer comorbidities were observed in
      the PPCI group of elderly patients presenting with STEMI.

PMID- 25870502
TI  - Impact of lipid disorders on mortality among Saudi patients with heart failure.
AB  - BACKGROUND: Dyslipidemia, a known cardiovascular risk factor, is extremely common
      among Saudis, both adults and children. The impact, however, of dyslipidemia and
      several other lipid disorders in patients with congestive heart failure in this
      particular population has not been documented. This study aims to fill the gap.
      METHODS: This retrospective, single center study was conducted at King Abdulaziz
      Medical City, Riyadh, Saudi Arabia. Of the 500 cases seen during the period
      between 2002 and 2008, 392 were included in the study. Charts were reviewed and
      information on medical history, medications, and lipid status were documented.
      RESULTS: Low HDL-cholesterol level was the most common lipid disorder with 82.9%,
      followed by hypertriglyceridemia (35.2%), atherogenic dyslipidemia (27.8%), and
      hypercholesterolemia (9.2%). Diabetes mellitus was the single most significant
      predictor of mortality (p = 0.001). Among the lipid disorders, only low levels of
      HDL-cholesterol contributed to significant mortality risk [OR 1.29 (Confidence
      Interval 1.04-1.59) (p-value < 0.01)] adjusted for age, gender and statin use.
      CONCLUSION: The results of this study suggest that emphasis should be on the
      elevation of HDL-cholesterol levels among subjects with congestive heart failure,
      without compromising any ongoing management of LDL-lowering drugs. Management
      should not be limited to conventional statin use and should promote other
      treatments to elevate HDL-cholesterol levels.

PMID- 25870503
TI  - Electrocardiographic methods for diagnosis and risk stratification in the Brugada
      syndrome.
AB  - The Brugada syndrome (BrS) is a malignant, genetically-determined, arrhythmic
      syndrome manifesting as syncope or sudden cardiac death (SCD) in individuals with
      structurally normal hearts. The diagnosis of the BrS is mainly based on the
      presence of a spontaneous or Na + channel blocker induced characteristic,
      electrocardiographic (ECG) pattern (type 1 or coved Brugada ECG pattern)
      typically seen in leads V1 and V2 recorded from the 4th to 2nd intercostal (i.c.)
      spaces. This pattern needs to be distinguished from similar ECG changes due to
      other causes (Brugada ECG phenocopies). This review focuses mainly on the ECG
      based methods for diagnosis and arrhythmia risk assessment in the BrS. Presently,
      the main unresolved clinical problem is the identification of those patients at
      high risk of SCD who need implantable cardioverter-defibrillator (ICD), which is
      the only therapy with proven efficacy. Current guidelines recommend ICD
      implantation only in patients with spontaneous type 1 ECG pattern, and either
      history of aborted cardiac arrest or documented sustained VT (class I), or
      syncope of arrhythmic origin (class IIa) because they are at high risk of
      recurrent arrhythmic events (up to 10% or more annually for those with aborted
      cardiac arrest). The majority of BrS patients are asymptomatic when diagnosed and
      considered to have low risk (around 0.5% annually) and therefore not indicated
      for ICD. The majority of SCD victims in the BrS, however, had no symptoms prior
      to the fatal event and therefore were not protected with an ICD. While some ECG
      markers such as QRS fragmentation, infero-lateral early repolarisation, and
      abnormal late potentials on signal-averaged ECG are known to be linked to
      increased arrhythmic risk, they are not sufficiently sensitive or specific.
      Potential novel ECG-based strategies for risk stratification are discussed based
      on computerised methods for depolarisation and repolarisation analysis, a
      composite approach targeting several major components of ventricular
      arrhythmogenesis, and the collection of large digital ECG databases in genotyped
      BrS patients and their relatives. 

PMID- 25870505
TI  - Successful retrieval of fractured pressure wire tip (FFR) by hybrid technique.
AB  - Coronary angiography and angioplasty are relatively safe procedures but not
      without complications. We report an interesting case of effort angina taken for
      angioplasty of the LCX and assessment of fractional flow reserve (FFR) for the
      LAD artery lesion in which the tip of the pressure wire was broken and embolised
      to the LCX while trying to retrieve it. This is the first case report using a
      hybrid technique with a slip catheter for the successful retrieval of a fractured
      FFR wire. 

PMID- 25870504
TI  - Invasive assessment modalities of unprotected left main stenosis.
AB  - Among all coronary lesions, the decision-making process for the treatment of
      unprotected left main (ULM) stem lesions is still challenging. Indeed, the
      optimal therapeutic strategy for patients with ULM disease remains controversial:
      coronary artery bypass grafting was established as the gold standard, but it is
      without doubt that percutaneous coronary intervention (PCI) performed by
      experienced operators achieves good results at long term follow up, especially in
      cases where the ostium and/or shaft of ULM are treated. Thanks to the widespread
      use of invasive assessment of atherothrombotic ULM stenosis, improved selection
      of PCI cases and techniques of stenting, better outcomes are now possible. This
      review seeks to define the place of PCI in ULM disease by describing the
      different modalities of ULM stenosis assessment. 

PMID- 25870506
TI  - Bilateral superior vena cava with right superior vena cava draining into left
      atrium.
AB  - Anomalies of systemic venous return are extremely heterogeneous congenital
      malformations with variable ranges from completely normal physiology to severe
      forms of right to left shunting requiring surgical treatment. Anomalous drainage
      of a right-sided superior vena cava (SVC) to the left atrium (LA) is one of the
      rarest variants of systemic venous return anomalies, characterized by right-to
      left shunt physiology and cyanosis. Here we report a 2 years old girl presented
      with cyanosis which was observed shortly after birth by her parents but not
      further investigated. She is otherwise active girl and with normal growth and
      development. Her clinical examination was unremarkable apart from mild clubbing
      of the fingers and low oxygen saturation of 88-90% in room air. Her ECG and chest
      X-ray were unremarkable. Echocardiography showed bilateral SVC connected by a
      small innominate vein. The right SVC drains directly into the LA while the left
      SVC drains into the right atrium (RA) via a dilated coronary sinus. There is a
      small superior sinus venosus type atrial septum defect (ASD) with left to right
      shunt. Also, there is partial anomalous pulmonary venous return with right upper
      and right middle pulmonary veins draining directly into the right SVC, which is
      connected to LA. The right lower pulmonary vein and left pulmonary veins drain
      directly to LA. The rest of her echocardiography demonstrated normal heart
      structures and function. This patient was referred for surgical correction,
      including baffling of the right SVC to the RA and closure of the ASD. We describe
      this case to highlight the importance of recognizing this rare anomalous systemic
      venous connection as one of the very rare causes of cyanosis in the pediatric age
      group as well as at older age. 

PMID- 25870507
TI  - Cardiac MRI findings of endomyocardial fibrosis (Loeffler's endocarditis) in a
      patient with rheumatoid arthritis.
AB  - Loeffler's endocarditis and cardiac manifestations of the hypereosinophilic
      syndrome (HES) are rare and difficult to diagnose. We report a case of in a 36
      year-old female with a history of rheumatoid arthritis with disabling dyspnea.
      The transthoracic echocardiogram demonstrated normal systolic cardiac functions
      and a left ventricular apical thrombus. However, using cardiovascular magnetic
      resonance (CMR) with inversion-recovery (IR) delayed enhancement, and cine steady
      state free precession (SSFP) sequences, we were able to clearly demonstrate
      endocardial fibrosis, tissue inflammation, apical ventricular hypertrophy, and LV
      thrombus that correlate with clinical findings. We believe cardiac MRI is more
      useful than transthoracic echocardiography in the diagnosis and management of HES
      and ultimately it obviated the need for biopsy to confirm the diagnosis. 

PMID- 25870508
TI  - Congenital absence of left atrial appendage: A case report and literature review.
AB  - Congenital absence of left atrial appendage (LAA) is an extremely rare entity. A
      50-year-old man with no past cardiac history was admitted with symptomatic atrial
      fibrillation (AF). Before subjecting him to direct current (DC) cardioversion,
      the patient underwent a transesophageal echocardiography (TEE) examination, but
      neither LAA nor a cardiac thrombus could be detected. Absence of both was
      confirmed by cardiac computer tomography (CT) and a cardiac magnetic resonance
      imaging (MRI) scan. The patient reverted to sinus rhythm with an uneventful
      synchronized biphasic DC shock of 100 joules. 

PMID- 25870509
TI  - Visible age-related signs in an Arab patient presenting with a myocardial
      infarction.

PMID- 25870510
TI  - Public Awareness of Oral and Pharyngeal Cancer: What Can a Dentist Do?

PMID- 25870511
TI  - What Can Parents Do? A Review of State Laws Regarding Decision Making for
      Adolescent Drug Abuse and Mental Health Treatment.
AB  - This study examined US state laws regarding parental and adolescent decision
      making for substance use and mental health inpatient and outpatient treatment.
      State statues for requiring parental consent favored mental health over drug
      abuse treatment and inpatient over outpatient modalities. Parental consent was
      sufficient in 53%-61% of the states for inpatient treatment, but only for 39% -
      46% of the states for outpatient treatment. State laws favored the rights of
      minors to access drug treatment without parental consent, and to do so at a
      younger age than for mental health treatment. Implications for how these laws may
      impact parents seeking help for their children are discussed.

PMID- 25870512
TI  - Lymphogranuloma venereum: diagnostic and treatment challenges.
AB  - Lymphogranuloma venereum is a sexually transmitted disease caused by L1, L2, and
      L3 serovars of Chlamydia trachomatis. In the last 10 years outbreaks have
      appeared in North America, Europe, and Australia in the form of proctitis among
      men who have sex with men. Three stages of disease have been described. The
      disease in primary stage may go undetected when only a painless papule, pustule,
      or ulceration appears. The diagnosis is difficult to establish on clinical
      grounds alone and frequently relies upon either serologic testing, culture, or
      more recently, nucleic acid amplification testing of direct specimens. A proper
      treatment regimen cures the infection and prevents further damage to tissues.
      Lymphogranuloma venereum causes potentially severe infections with possibly
      irreversible sequels if adequate treatment is not begun promptly. Early and
      accurate diagnosis is essential. Doxycycline is the drug of choice. Pregnant and
      lactating women should be treated with erythromycin or azithromycin. Patient must
      be followed up during the treatment, until disease signs and symptoms have
      resolved. Repeated testing for syphilis, hepatitis B and C, and HIV to detect
      early infection should be performed. 

PMID- 25870513
TI  - The impact of chronic pain on direct medical utilization and costs in chronic
      obstructive pulmonary disease.
AB  - OBJECTIVE: To examine how pain affects health care utilization and direct medical
      costs in individuals with chronic obstructive pulmonary disease (COPD) compared
      to patients with other chronic diseases. STUDY DESIGN: A retrospective cohort
      analysis using administrative data of a managed health care system in the
      Southwestern US for years 2006-2010. METHODS: COPD patients age >=40 years were
      matched to similar patients with other chronic conditions on age, sex, insurance
      type, and a health care event (outpatient visit, emergency department visit, or
      inpatient stay). Chronic pain was indicated by pain-associated diagnoses and
      procedures, or fills for prescription pain medications. The study population was
      also stratified into those with and without chronic pain to examine clinical
      factors and costs associated with chronic pain. RESULTS: Seven thousand nine
      hundred and fifty-two COPD patients (mean age 69 years, 58% women) were matched
      to 15,904 patients with other chronic disease. COPD patients had significantly
      higher utilization for pain-related services and for overall services. COPD
      patients had a higher prevalence of any pain medication use over a 12-month
      period (41.2% versus 31.5%) and, among those using pain medications, a higher
      mean number of pain medication prescription fills (10.1 versus 6.4). Factors
      associated with chronic pain included age 40-65 years, being female, having more
      than one chronic morbidity, insurance type, some emergency department or hospital
      utilization, and having either COPD, heart failure, arthritis, or stroke. Among
      COPD patients, those with chronic pain had a mean annual direct cost for overall
      utilization of $24,261 versus $10,390 among those without chronic pain (P<0.0001
      for all comparisons). CONCLUSION: COPD patients have substantially more
      utilization for pain medications and pain-related procedures than those with most
      other chronic diseases. Total direct medical costs among COPD patients who have
      chronic pain are more than double those of COPD patients without chronic pain.
      Pain management may be an opportunity for better and more cost-effective care for
      COPD patients.

PMID- 25870514
TI  - Pattern of arrhythmias among Nigerians with congestive heart failure.
AB  - BACKGROUND: In patients with heart failure, death is often sudden due to life
      threatening arrhythmias. This work was carried out to evaluate the pattern of
      arrhythmias in Nigerians with heart failure. MATERIALS AND METHODS: Thirty
      subjects with congestive heart failure (CHF), 30 subjects with hypertensive heart
      disease, and 15 normal subjects with no obvious features of heart disease were
      evaluated with resting and 24-hour electrocardiographic monitoring and
      transthoracic echocardiography. Data were analyzed with one-way analysis of
      variance with post hoc Duncan's analysis, Fisher's exact test, and linear
      regression analysis using SPSS version 16. RESULTS: CHF subjects had more
      instances of supraventricular tachycardia (P=0.005), ventricular extrasystoles
      (P<0.001), bigeminy (P<0.001), trigeminy (P<0.001), couplets (P<0.001), triplets
      (P<0.001), and nonsustained ventricular tachycardia (VT) (P=0.003) than the other
      two control groups. They also showed a significantly longer VT duration (4.6+/
      5.6 seconds) compared with the other groups (P<0.001). Linear regression analysis
      showed a significant direct relationship between VT and the maximum number of
      ventricular extrasystoles per hour (P=0.001). CONCLUSION: Cardiac arrhythmias are
      common in subjects with CHF and are more frequent when compared with patients
      with hypertensive heart disease and normal subjects.

PMID- 25870515
TI  - Validity of reaction to severe stress and adjustment disorder diagnoses in the
      Danish Psychiatric Central Research Registry.
AB  - AIMS: To assess the validity of reaction to severe stress and adjustment disorder
      diagnoses registered in the Danish Psychiatric Central Research Register (DPCRR),
      to examine the documentation of stressful and traumatic events in the medical
      records, and to investigate the occurrence of stress diagnoses among persons not
      registered in the DPCRR. METHODS: Among 101,633 patients diagnosed with
      International Classification of Diseases, 10th Edition (ICD-10) F43 diagnoses
      between 1995 and 2011, we selected 50 patients from two hospitals (100 total),
      comprising one above and one below median age for each diagnosis for five time
      periods, and reviewed their medical records. We calculated the positive
      predictive value, comparing registration in the DPCRR with the original medical
      records, and captured data on stressful life events. Two general practitioners
      were queried about 50 patients without a stress diagnosis in the DPCRR, regarding
      whether they had ever received a stress diagnosis. RESULTS: The positive
      predictive value was 58% for acute stress reaction, 83% for posttraumatic stress
      disorder, 94% for adjustment disorder, 71% for other reactions to severe stress,
      and 68% for reaction to severe stress, unspecified. In 80% of the records, a
      stressful or traumatic event was noted. Of 100 patients without an F43 diagnosis
      in the DPCRR, seven had a stress diagnosis. CONCLUSION: The DPCRR represents a
      valid and comprehensive resource for research on reaction to severe stress and
      adjustment disorders, particularly for posttraumatic stress disorder and
      adjustment disorder.

PMID- 25870516
TI  - A case of isolated adrenocorticotropic hormone deficiency: a rare but possible
      cause of hypercalcemia.
AB  - A 52-year-old woman presented with an 8-month history of epigastric pain, nausea,
      and weight loss. One year before, she was diagnosed with breast cancer. During
      the postoperative chemotherapy, she developed epigastric pain and nausea. As a
      result, she gradually lost 12 kg of her body weight. We performed upper
      gastrointestinal endoscopy, which revealed mild erosive gastritis. After the
      treatment with a proton pump inhibitor, her symptoms persisted. Before the
      admission, mild hypercalcemia was pointed out. Fluid replacement didn't improve
      hypercalcemia. We assessed adrenocortical function, which showed that her serum
      cortisol and adrenocorticotropic hormone were decreased. Through loading tests,
      we established diagnosis of isolated adrenocorticotropic hormone deficiency. She
      was treated with hydrocortisone. Soon after the treatment, her serum calcium
      level returned to normal and her symptoms improved. In a case of hypercalcemia
      unresponsive to fluid replacement, we recommend ruling out adrenal insufficiency
      after excluding more common diseases which induce hypercalcemia. 

PMID- 25870518
TI  - The feasibility of using electronic clinical outcome assessments in people with
      schizophrenia and their informal caregivers.
AB  - Many clinical outcome assessments (COAs) were originally developed for completion
      via pen and paper. However, in recent years there have been movements toward
      electronic capture of such data in an effort to reduce missing data, provide time
      stamped records, minimize administrative burden, and avoid secondary data entry
      errors. Although established in many patient populations, the implications of
      using electronic COAs in schizophrenia are unknown. In accordance with
      International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Task
      Force recommendations, in-depth cognitive debriefing and usability interviews
      were conducted with people with schizophrenia (n=12), their informal (unpaid)
      caregivers (n=12), and research support staff (n=6) to assess the suitability of
      administration of various electronic COA measures using an electronic tablet
      device. Minimal issues were encountered by participants when completing or
      administering the COAs in electronic format, with many finding it easier to
      complete instruments in this mode than by pen and paper. The majority of issues
      reported were specific to the device functionality rather than the electronic
      mode of administration. Findings support data collection via electronic tablet in
      people with schizophrenia and their caregivers. The appropriateness of other
      forms of electronic data capture (eg, smartphones, interactive voice response
      systems, etc) is a topic for future investigation. 

PMID- 25870517
TI  - Expanding antitumor therapeutic windows by targeting cancer-specific nicotinamide
      adenine dinucleotide phosphate-biogenesis pathways.
AB  - Nicotinamide adenine dinucleotide phosphate (NADPH) biogenesis is an essential
      mechanism by which both normal and cancer cells maintain redox balance. While
      antitumor approaches to treat cancers through elevated reactive oxygen species
      (ROS) are not new ideas, depleting specific NADPH-biogenesis pathways that
      control recovery and repair pathways are novel, viable approaches to enhance
      cancer therapy. However, to elicit efficacious therapies exploiting NADPH
      biogenic pathways, it is crucial to understand and specifically define the roles
      of NADPH-biogenesis pathways used by cancer cells for survival or recovery from
      cell stress. It is equally important to select NADPH-biogenic pathways that are
      expendable or not utilized in normal tissue to avoid unwanted toxicity. Here, we
      address recent literature that demonstrates specific tumor-selective NADPH
      biogenesis pathways that can be exploited using agents that target specific
      cancer cell pathways normally not utilized in normal cells. Defining NADPH
      biogenesis profiles of specific cancer-types should enable novel strategies to
      exploit these therapeutic windows for increased efficacy against recalcitrant
      neoplastic disease, such as pancreatic cancers. Accomplishing the goal of using
      ROS as a weapon against cancer cells will also require agents, such as NQO1
      bioactivatable drugs, that selectively induce elevated ROS levels in cancer
      cells, while normal cells are protected. 

PMID- 25870519
TI  - Pragmatic measurement of health satisfaction in people with type 2 diabetes
      mellitus using the Current Health Satisfaction Questionnaire.
AB  - BACKGROUND: The concept of diabetes-related health satisfaction encompasses
      issues specifically related to living with diabetes (eg, blood glucose, blood
      pressure levels, body weight). Health satisfaction is more specific than overall
      health-related quality of life because it considers disease-related factors, and
      is different from diabetes treatment satisfaction because it addresses issues not
      specifically related to treatment. Low levels of health satisfaction in people
      with type 2 diabetes mellitus (T2DM) may negatively affect self-care behaviors
      and treatment outcomes; however, there are currently no instruments available to
      assess health satisfaction in this population. This study assessed the
      measurement properties of a newly constructed, 14-item Current Health
      Satisfaction Questionnaire (CHES-Q) designed to assess diabetes-related health
      satisfaction and knowledge of the disease and important laboratory results.
      METHODS: In-depth interviews were conducted in 23 adults with T2DM to confirm the
      content and clarity of the CHES-Q. The revised instrument was administered to
      1,015 individuals with T2DM, along with supplemental questionnaires, including
      the Short Form-36. All subjects completed the questionnaires again 3 to 7 days
      later. CHES-Q test-retest reliability, construct validity, and known-groups
      validity were evaluated. RESULTS: In general, respondents found the CHES-Q to be
      clear and comprehensive. Test-retest reliability was generally acceptable for all
      items (>=0.70), except for three that fell just below the widely accepted cut
      point of 0.70 (range 0.63-0.69). Convergent and divergent validity was
      demonstrated based on hypothesized correlations with the Short Form-36. Known
      groups validity was confirmed for most CHES-Q items when respondents were split
      into groups known to differ clinically by body mass index, disease severity, or
      glycated hemoglobin. CONCLUSION: Health satisfaction is a unique and important
      concept to consider when developing individualized strategies for managing T2DM
      because health satisfaction is a key element of patient-centered care. The CHES-Q
      allows for the pragmatic assessment of many aspects of diabetes-related health
      satisfaction in a single questionnaire.

PMID- 25870520
TI  - Social disparities among youth and the impact on their health.
AB  - PURPOSE: Social disparities among youth have been recognized as an important
      influence on disease risk later in the life cycle. Despite this, social problems
      are seldom assessed in a clinical setting. The primary objective of our study was
      to evaluate the impact of social disparities on the health of youth. METHODS: A
      self-directed, web-based screening system was used to identify social disparities
      along seven social domains. Participants included youth, aged 15-24 years,
      recruited from an urban hospital clinic. The main outcome variable, self-rated
      health, was captured on a 5-point Likert scale. Univariable and multivariable
      regression models adjusted for sex, age, and race/ethnicity were implemented to
      assess the association between social problems and self-rated health. Correlation
      between social disparity problems was estimated using phi coefficient. RESULTS:
      Among 383 participants, 297 (78%) reported at least one social problem. The
      correlation among social disparity problems was low. Social disparities had an
      independent effect on self-rated health, and, in a fully adjusted model,
      disparities in health care access and food insecurity remained significant. The
      presence of even one social problem was associated with a decrease in overall
      health (beta=0.68, P<0.01). CONCLUSION: There is a high burden of social
      disparities among our youth urban hospital population. The presence of even one
      social problem increases the risk of worsening self-rated health. Evaluating the
      social disparities among youth in the medical setting can help elucidate factors
      that negatively affect patients' health.

PMID- 25870521
TI  - Semiparametric transformation models for causal inference in time to event
      studies with all-or-nothing compliance.
AB  - We consider causal inference in randomized survival studies with right censored
      outcomes and all-or-nothing compliance, using semiparametric transformation
      models to estimate the distribution of survival times in treatment and control
      groups, conditional on covariates and latent compliance type. Estimands depending
      on these distributions, for example, the complier average causal effect (CACE),
      the complier effect on survival beyond time t, and the complier quantile effect
      are then considered. Maximum likelihood is used to estimate the parameters of the
      transformation models, using a specially designed expectation-maximization (EM)
      algorithm to overcome the computational difficulties created by the mixture
      structure of the problem and the infinite dimensional parameter in the
      transformation models. The estimators are shown to be consistent, asymptotically
      normal, and semiparametrically efficient. Inferential procedures for the causal
      parameters are developed. A simulation study is conducted to evaluate the finite
      sample performance of the estimated causal parameters. We also apply our
      methodology to a randomized study conducted by the Health Insurance Plan of
      Greater New York to assess the reduction in breast cancer mortality due to
      screening.

PMID- 25870522
TI  - Effectiveness of multifaceted and tailored strategies to implement a fall
      prevention guideline into acute care nursing practice: a before-and-after, mixed
      method study using a participatory action research approach.
AB  - BACKGROUND: Research- and/or evidence-based knowledge are not routinely adopted
      in healthcare and nursing practice. It is also unclear which implementation
      strategies are effective in nursing practice and what expenditures of time and
      money are required for the successful implementation of clinical practice
      guidelines (CPGs). The aim in this study was to assess the effectiveness and
      required time investment of multifaceted and tailored strategies for implementing
      an evidence-based fall-prevention guideline (Falls CPG) into nursing practice in
      an acute care hospital setting. METHODS: A before-and-after, mixed-method design
      was used within a participatory action research approach (PAR). The study was
      carried out in two departments of an Austrian university teaching hospital and
      included all graduate and assistant nurses. Data were collected through a
      questionnaire, group discussions and semi-structured interviews. Qualitative data
      were content-analysed using a template based on the Consolidated Framework for
      Implementation Research (CFIR), which also served as a theoretical framework for
      the study. Quantitative data were descriptively analysed using appropriate tests
      for independent groups. RESULTS: By applying multifaceted and tailored
      implementation strategies, the graduate and assistant nurses' knowledge on fall
      prevention, how to access the Falls CPG and the guideline itself increased
      significantly between baseline and final assessment (p <= .001). Qualitative data
      also revealed an increase in participant awareness of fall prevention. A baseline
      positive attitude towards guidelines improved significantly towards the end of
      the project (p = .001). Required fall prevention equipment like baby monitors or
      one-way glide sheets were available for use and any required environmental
      adaptations, e.g. a handrail in the corridor, were made. Hospital nursing
      personnel (approximately 150) invested a total of 1192 hours of working time over
      the course of the project. CONCLUSIONS: Multifaceted strategies tailored to the
      specific setting within a PAR approach and guided by the CFIR enabled the
      effective implementation of a CPG into acute care nursing practice. Nursing
      managers now have sound knowledge of the time resources required for CPG
      implementation.

PMID- 25870523
TI  - Frequency of class 1 integron in Escherichia coli strains isolated from patients
      with urinary tract infections in north of iran.
AB  - BACKGROUND: Due to the importance of antibiotic resistance in E.coli and the
      possible role of integrons in creating of resistance, this study was performed to
      survey of class 1 integron in E. coli strains and their resistance to three
      routinely used antibiotics. METHODS: In this cross-sectional study, 100 strains
      of E. coli were isolated from patients with Urinary tract infection. After
      diagnosis of bacteria, genomes were extracted. Then, presence of integron class 1
      was evaluated by using PCR. Antibiotic susceptibility testing method, the micro
      dilution broth was performed according to the standard CLSI2010. Data were
      analyzed using SPSS16 software. RESULT: Out of the total number of 100 E. coli
      cases, 22 cases (22%) had class 1 integron. Resistance against cotrimoxazol,
      cefixime and ciprofloxacin antibiotics were 67%, 34% and 34% respectively. In 22
      E. coli cases positive for integron class1 gene, resistance against three
      antibiotics were 100%, 95.45% and 90.90% respectively, which is statistically
      significant (p < 0.05). CONCLUSION: Resistance level against antibiotics in
      samples containing class 1 integron were significantly higher than those lacking
      this gene, which may be confirm the present of class 1 integron in creation of
      clinical strains with resistance to this antibiotics. Using suitable antibiotics
      may be preventing transmission of resistance genes through integrons.

PMID- 25870524
TI  - Universal neonatal hearing screening in Albania, 2009-2012.
AB  - AIM: Universal neonatal hearing screening Project started in Albania for the
      first time in January 2009. It was made possible by the support of Magis, an
      Italian NGO, as a grant of Italian government to the Albanian health system. The
      aim of this study was to assess the prevalence of PCHI in Albania. METHODS:
      Universal neonatal hearing screening in Albania started on January 2009 until
      December 2012. Overall, 47341 newborns were tested. The screening covered the
      three main cities of Albania; Tirana, Shkodra and Fier. RESULTS: Overall, 93
      babies resulted with bilateral hearing loss after the two steps screening. In
      total, 85 babies had hearing aids, 8 babies decided to get medical treatment
      abroad. The incidence at the end of the project is 2.1 babies with bilateral
      hearing impairment per 1000 births/year (2.1/1000 births). CONCLUSION: Our
      findings are generally in line with previous reports on this matter. Future
      studies in Albania should be conducted to assess the prevalence and determinants
      of PCHI in Albania and in other transitional settings.

PMID- 25870525
TI  - Psoriasis and dyslipidemia.
AB  - INTRODUCTION: Psoriasis is a chronic skin ailment, which can be connected with
      other ailments including dyslipidemia. EXAMINEES AND METHODS: Research included
      70 patients affected by psoriasis. Both genders, above 18 years of age. Average
      age of the respondents was 47.14 (SD= +/-15.41), which consisted of 36 men
      (51.43%) and 34 women (48.57%). The average duration of psoriasis was 15.52 (SD=
      +/-12.54) years. RESULTS: Frequency of dyslipidemia on those affected by
      psoriasis was 62.85%. Most often it was hypertriglyceridemia (39%) and
      hypertriglyceridemia with a lowered value of HDL (36%), average age of those
      affected by psoriasis with dyslipidemia was 48.76 years (SD= +/-14.72), and the
      average duration of the basic disease was 16.15 years (SD= +/-12.63), the average
      values of the PASI score were 16.65. Increase in values of PASI score and
      dyslipidemia were statistically significantly connected (r=0.41; p=0.0001).
      CONCLUSION: Psoriasis is connected with dyslipidemia.

PMID- 25870526
TI  - Relationship between ADHD and depression among university students in macedonia.
AB  - INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) is a
      neurobehavioral developmental disorder usually diagnosed in children, with
      appearance of the first symptoms before the age of seven years. The disorder is
      characterized by inattention and/or impulsivity and hyperactivity that can
      seriously affect many aspects of behavior and performance at school. ADHD can be
      associated with comorbidities, such as oppositional defiant disorder, conduct
      disorder, anxiety or depression. MATERIAL AND METHODS: The study was done on a
      sample of 500 university students. For the measurement of ADHD symptoms, the ADHD
      Adult Self-report Scale was used and for depression measurement DASS. RESULTS:
      The results of this screening study showed that ADHD is highly significant
      associated with gender (p = 0.0004). Men more often than women have this kind of
      disorder. Female students have attention subtype deficit, while man student have
      often hyperactivity/impulsivity disorder and combined subtype due to
      psychological, temperament and character gender differences among boys and girls.
      Female examinees are significantly (p=0.028) more often depressed compared to
      male examinees. CONCLUSION: The examined correlations are positive ones or
      direct, meaning that by increasing the values of the scores from both subscales
      from the Evaluation ADHD Scale one also increases the scores from the Depression
      Scale, and vice versa. For a value of p=0.001 and p=0.004 these correlations are
      statistically highly significant, in other words highly important.

PMID- 25870527
TI  - Clinical and Epidemiological Characteristics of HIV Infection/AIDS in
      Hospitalized Patients.
AB  - INTRODUCTION: More than three decades after recognition of acquired
      immunodeficiency syndrome (AIDS) in the United States, the pandemic of human
      immunodeficiency virus (HIV) infection has dramatically changed the global burden
      of disease. AIM: The main goal of this research is retrospective analysis of
      epidemiological and clinical characteristics of 28 HIV infected patients, who
      were diagnosed and treated at the Clinic for Infectious Diseases in University
      Clinical Center Tuzla in the period from 1996 until the end of 2013. SUBJECTS AND
      METHODS: Retrospective analysis was performed using the medical records of 28 HIV
      infected persons. Two rapid tests were used for HIV testing: OraQuick Advance
      test, Vikia HIV1/2, Elisa combo test, HIV RNA test. AIDS disease was determined
      by using the criteria from WHO. RESULTS: Among a total of 28 HIV-infected
      persons, 23 (82.14%) were males and 5 (17.86%) were females, with the male:
      female ratio of 4,6:1. In terms of the transmission route, a large proportion of
      cases were infected through heterosexual contact 19 (67.86%). At the time of the
      first visit, 16 (57.15%) patients showed asymptomatic HIV infection, 4 (14.28%)
      HIV infection with symptoms other than the AIDS defining diseases, and 8 (28.57)
      had AIDS. At the time of first hospital visit, the CD4 + cells count ranged from
      40 to 1795/ul (conducted in 19 patients), and mean value of CD4 + cells was
      365,31/ul, and mean HIV RNA titer was 287 118 copies/ml3. Of 28 HIV-infected
      persons 39 cases of opportunistic diseases developed in 12 patients (42.9%). In
      terms of the frequency of opportunistic diseases, tuberculosis (12 cases, 42.9%).
      Among a total of 28 HIV-infected patients, 6 (21.4%) of them died. CONCLUSION:
      This study characterizes the epidemiological and clinical patterns of HIV
      infected patients in Tuzla region of Bosnia and Herzegovina to accurately
      understand HIV infection/AIDS in our region, in the hope to contribute in the
      establishment of effective HIV guidelines in the Tuzla region of B&H in the
      future.

PMID- 25870528
TI  - Rate of medical errors in affiliated hospitals of mazandaran university of
      medical sciences.
AB  - INTRODUCTION: Health care organizations are highly specialized and complex. Thus
      we may expect the adverse events will inevitably occur. Building a medical error
      reporting system to analyze the reported preventable adverse events and learn
      from their results can help to prevent the repeat of these events. The medical
      errors which were reported to the Clinical Governance's office of Mazandaran
      University of Medical Sciences (MazUMS) in years 2011-2012 were analyzed. METHODS
      AND MATERIALS: This is a descriptive retrospective study in which 18 public
      hospitals were participated. The instrument of data collection was checklist that
      was designed by the Ministry of Health of Iran. Variables were type of hospital,
      unit of hospital, season, severity of event and type of error. The data were
      analyzed with SPSS software. RESULTS: Of 317966 admissions 182 cases, about
      0.06%, medical error reported of which most of the reports (%51.6) were from non-
      teaching hospitals. Among various units of hospital, the highest frequency of
      medical error was related to surgical unit (%42.3). The frequency of medical
      error according to the type of error was also evaluated of which the highest
      frequency was related to inappropriate and no care (totally 37%) and medication
      error 28%. We also analyzed the data with respect to the effect of the error on a
      patient of which the highest frequency was related to minor effect (44.5%).
      CONCLUSION: The results showed that a wide variety of errors. Encourage and
      revision of the reporting process will be result to know more data for prevention
      of them.

PMID- 25870529
TI  - The role of human resources management on enhancing the teaching skills of
      faculty members.
AB  - INTRODUCTION: Human performance in organizations reflects on the knowledge,
      skills, behaviors, and values. Since the abilities and skills will help the
      organization to better performance and productivity, any expenditure on education
      and development is a long term investment that as long as the organization can
      benefit from it. The aim of this research is assessment of influence of
      structured workshops by resource management at different levels of acquaintance,
      skills, updates, and upgrades in field of teaching before teaching for invited
      professors and tuition. METHODOLOGY: So in a case study in the first semester of
      the academic year of 91- 92, 30 teachers with no teaching experience in tuition
      PNU after internal interview was selected as a sample. Then their awareness of
      indicators of effective teaching and training allowance of two categories before
      and after the workshop assessed and evaluated by a questionnaire. RESULTS: The
      results of descriptive and inferential statistical analysis indicates that the
      52/4% of the professors of the age group 25-30, and 38/1% are in the age group 31
      36. Also 76/2% percent of teachers have graduated from the National University
      and the rest of the teacher have graduated from Azad or Payamenoor University.
      Also there is significant difference between the knowledge of laws and
      regulations and effective teaching index before and after the workshop on four
      indicators: evaluation of students, teaching methods, planning, behavioral
      patterns and rules and regulations PNU. So it shows the impact of targeted
      workshops and the role of education experts in the process of recreating human
      resource management in higher education systems.

PMID- 25870530
TI  - The Relationship between Field Dependent-Independent Cognitive Style and
      Understanding of English Text Reading and Academic Success.
AB  - BACKGROUND: The learning styles are the distinctive learners' strategies for
      information processing and discovering new concepts. One of the most important
      kinds of learning styles is the Witkin's theory of field dependence-independence
      cognitive style. OBJECTIVE: This study seeks to find the relationship between
      field dependence -independence cognitive style and English text reading
      comprehension, learning English as a foreign language, academic achievement and
      the choice of academic courses. METHODS: In this study, 305 students (both girls
      and boys) studying at the junior level at high school in Sari were randomly
      selected through multistage selection who responded to Group Embedded Figures
      Test (GEFT). RESULTS: The data analysis was conducted by using regression
      analysis which showed that FDI cognitive styles determined the changes in
      dependant variables of reading comprehension score, learning English and the
      total average with the respective values of %8.8, %9.2 and %11.6 (p <0.05).
      CONCLUSION: Regarding the findings, it can be concluded that the more field
      independent, the higher the reading comprehension skills and learning English and
      the more academic achievement will result. The results of this study can help in
      selecting students' courses and also better directing the learners to improve
      their learning.

PMID- 25870531
TI  - Efficacy and safety of a fixed combination of tramadol and paracetamol
      (acetaminophen) as pain therapy within palliative medicine.
AB  - GOAL: The goal of the research was to determine the efficacy of a fixed
      combination of tramadol and paracetamol (acetaminophen) in the treatment of pain
      of patients with the advanced stage of cancer. MATERIAL AND METHODS: A
      prospective study was conducted at the Center for Palliative Care, University
      Clinical Center Tuzla, Bosnia and Herzegovina, from January 1(st) to December
      31(st) 2013. A total of 353 patients who were treated with a fixed combination of
      tramadol and acetaminophen (37.5 mg and 325 mg) at the initial dosage 3x1 tablet
      (112.5 mg tramadol and 975 mg acetaminophen) for pain intensity 4, up to 4x2
      tablets (300 mg of tramadol and 2600 mg paracetamol) for pain intensity 7 and 8.
      If the patient during previous day has two or more pain episodes that required a
      "rescue dose" of tramadol, increased was the dose of fixed combination tramadol
      and acetaminophen to a maximum of 8 tablets daily (300 mg of tramadol and 2600 mg
      paracetamol). Statistical analysis was performed by biomedical software MedCalc
      for Windows version 9.4.2.0. The difference was considered significant for
      P<0.05. RESULTS: The average duration of treatment with a fixed combination
      tramadol and acetaminophen was 57 days (13-330 days). Already after 24 hours of
      treatment the average pain score was significantly lower (p<0.0001) compared to
      the admission day [5.00 (4:00 to 8:00) during the first days versus 2.00 (1:00 to
      7:00) during the second day of treatment]. The average dose of the fixed
      combination tramadol and acetaminophen tablets was 4.8 +/- 1.8 (180 mg of
      tramadol and 1560 mg paracetamol). Side effects, in the treatment of pain with a
      fixed combination tramadol and acetaminophen, were found in 29.18% of patients,
      with a predominance of nausea and vomiting. CONCLUSION: Fixed combination of
      tramadol and acetaminophen can be used as an effective combination in the
      treatment of chronic cancer pain, with frequent dose evaluation and mild side
      effects.

PMID- 25870532
TI  - Punica granatum juice effects on oxidative stress in severe physical activity.
AB  - AIM: The aim of this study was to investigate Punica granatum juice effects on
      oxidative stress in young healthy males during severe physical activity. METHODS:
      Our subjects were selected from healthy males at 18 - 24 years. They were
      enrolled and randomly distributed into control and supplemented groups. 240 ml of
      Punica granatum juice and tap water were given to supplement and control groups
      daily for two weeks, respectively. Fasting blood samples were taken at the
      starting and the end of two weeks of intervention. Subjects were given once
      severe physical activity and then fasting blood samples were taken. Fasting blood
      samples were used for testing of oxidative and antioxidative factors. Data were
      analyzed using descriptive statistical tests, paired samples t-test, and
      independent samples t-test. RESULTS: The levels of arylesterase, superoxide
      dismutase, glutathione peroxidase and total antioxidant capacity after severe
      physical activity in supplement group were significantly increased (p<0.05),
      while the content of malondialdehyde showed a significantly decrease in
      comparison to control group (p<0.05). CONCLUSION: Our findings indicate that
      regular intake of Punica granatum juice significantly modulates oxidative stress
      and thus protects against severe physical activity oxidative injury in young
      healthy males.

PMID- 25870533
TI  - Roots of pharmacy practice in bosnia and herzegovina from the ottoman and austro
      hungarian period: attars' mission for pharmaceutical care.
AB  - Significant role in how they played, and Jews Sephardim who came to Bosnia from
      Spain and Portugal in the late 15th and early 16th centuries. It is those were
      the first owners of districts-Shop herbs or pharmacy. Along with them were
      developed and Muslim attars, who founded and attars marketplace in Sarajevo.
      Experience and knowledge in the domain of medicine and healing practiced by old
      Bosnian Sephardim been acquired for centuries, is now mainly found on the
      shelves. 

PMID- 25870534
TI  - Efficiency of implementation of the bologna process at medical faculty,
      university of sarajevo.
AB  - INTRODUCTION: At the moment at Medical Faculty, University of Sarajevo,
      simultaneously exist two systems of teaching process, the old (pre-Bologna) and
      Bologna process. GOAL: To show efficiency and justification of use of Bologna
      process at Medical Faculty, University of Sarajevo, through the prism of actual
      beneficiaries of this process, students, assessment of quality of medical
      education, and comparison of results of the teaching process evaluation between
      students studying according to the Bologna process and the old system. MATERIALS
      AND METHODS: The study included period from 2012 to 2014, and had prospective
      character. Students of final (sixth) year were included, the last three
      generations of pre-Bologna, and three generations of the Bologna process, which
      completed their studies successfully. The study included 365 students (177 under
      the old system and 188 under the Bologna process), who had answered prepared
      questionnaire. RESULTS: The presence of large number of female students, in both
      systems is significant. There were significant differences in opinion of students
      regarding the quality of space for administration and labor administration,
      informatization of the teaching process, the opinion of the objectivity of
      teachers in the assessment of the examination, and on-line access to their
      content. (p <0.05). DISCUSSION: The Bologna process, with all its guidelines, was
      never to the maximum implemented in the teaching faculties, mostly because of the
      lack of funds and infrastructure that couldn't fully comply with all the
      privileges of the Bologna process. CONCLUSION: Bologna process on this principle,
      has brought mediocrity, of which we have tried to escape. New school year,
      brings, and the new Bologna process, a new curriculum, a large number of new
      classes, systematization of the material, with simultaneous correction necessary
      in one hand in teaching, and in other hand in students themselves.

PMID- 25870535
TI  - Sex differences in feeding behavior in rats: the relationship with neuronal
      activation in the hypothalamus.
AB  - There is general agreement that the central nervous system in rodents differs
      between sexes due to the presence of gonadal steroid hormone during
      differentiation. Sex differences in feeding seem to occur among species, and
      responses to fasting (i.e., starvation), gonadal steroids (i.e., testosterone and
      estradiol), and diet (i.e., western-style diet) vary significantly between sexes.
      The hypothalamus is the center for controlling feeding behavior. We examined the
      activation of feeding-related peptides in neurons in the hypothalamus.
      Phosphorylation of cyclic AMP response element-binding protein (CREB) is a good
      marker for neural activation, as is the Fos antigen. Therefore, we predicted that
      sex differences in the activity of melanin-concentrating hormone (MCH) neurons
      would be associated with feeding behavior. We determined the response of MCH
      neurons to glucose in the lateral hypothalamic area (LHA) and our results
      suggested MCH neurons play an important role in sex differences in feeding
      behavior. In addition, fasting increased the number of orexin neurons harboring
      phosphorylated CREB in female rats (regardless of the estrous day), but not male
      rats. Glucose injection decreased the number of these neurons with phosphorylated
      CREB in fasted female rats. Finally, under normal spontaneous food intake, MCH
      neurons, but not orexin neurons, expressed phosphorylated CREB. These sex
      differences in response to fasting and glucose, as well as under normal
      conditions, suggest a vulnerability to metabolic challenges in females. 

PMID- 25870536
TI  - Proper housing conditions in experimental stroke studies-special emphasis on
      environmental enrichment.
AB  - Environmental enrichment provides laboratory animals with novelty and extra
      space, allowing different forms of multisensory stimulation ranging from social
      grouping to enhanced motor activity. At the extreme end of the spectrum, one can
      have a super-enriched environment. Environmental enrichment is believed to result
      in improved cognitive and sensorimotor functions both in naive rodents and in
      animals with brain lesions such as those occurring after a stroke. Robust
      behavioral effects in animals which have suffered a stroke are probably related
      not only to neuronal plasticity in the perilesional cortex but also in remote
      brain areas. There is emerging evidence to suggest that testing restorative
      therapies in an enriched environment can maximize treatment effects, e.g., the
      perilesional milieu seems to be more receptive to concomitant pharmacotherapy
      and/or cell therapy. This review provides an updated overview on the effect of an
      enriched environment in stroke animals from the practical points to be considered
      when planning experiments to the mechanisms explaining why combined therapies can
      contribute to behavioral improvement in a synergistic manner. 

PMID- 25870537
TI  - Living without insulin: the role of leptin signaling in the hypothalamus.
AB  - Since its discovery in 1922, insulin has been thought to be required for normal
      metabolic homeostasis and survival. However, this view would need to be revised
      as recent results from different laboratories have convincingly indicated that
      life without insulin is possible in rodent models. These data indicate that
      particular neuronal circuitries, which include hypothalamic leptin-responsive
      neurons, are empowered with the capability of permitting life in complete absence
      of insulin. Here, we review the neuronal and peripheral mechanisms by which
      leptin signaling in the central nervous system (CNS) regulates glucose metabolism
      in an insulin-independent manner. 

PMID- 25870539
TI  - Pharmacological blockade of the fatty acid amide hydrolase (FAAH) alters neural
      proliferation, apoptosis and gliosis in the rat hippocampus, hypothalamus and
      striatum in a negative energy context.
AB  - Endocannabinoids participate in the control of neurogenesis, neural cell death
      and gliosis. The pharmacological effect of the fatty acid amide hydrolase (FAAH)
      inhibitor URB597, which limits the endocannabinoid degradation, was investigated
      in the present study. Cell proliferation (phospho-H3(+) or BrdU(+) cells) of the
      main adult neurogenic zones as well as apoptosis (cleaved caspase-3(+)),
      astroglia (GFAP(+)), and microglia (Iba1(+) cells) were analyzed in the
      hippocampus, hypothalamus and striatum of rats intraperitoneally treated with
      URB597 (0.3 mg/kg/day) at one dose/4-days resting or 5 doses (1 dose/day).
      Repeated URB597 treatment increased the plasma levels of the N-acylethanolamines
      oleoylethanolamide, palmitoylethanolamide and arachidonoylethanolamine, reduced
      the plasma levels of glucose, triglycerides and cholesterol, and induced a
      transitory body weight decrease. The hippocampi of repeated URB597-treated rats
      showed a reduced number of phospho-H3(+) and BrdU(+) subgranular cells as well as
      GFAP(+), Iba1(+) and cleaved caspase-3(+) cells, which was accompanied with
      decreased hippocampal expression of the cannabinoid CB1 receptor gene Cnr1 and
      Faah. In the hypothalami of these rats, the number of phospho-H3(+), GFAP(+) and
      3-weeks-old BrdU(+) cells was specifically decreased. The reduced striatal
      expression of CB1 receptor in repeated URB597-treated rats was only associated
      with a reduced apoptosis. In contrast, the striatum of acute URB597-treated rats
      showed an increased number of subventricular proliferative, astroglial and
      apoptotic cells, which was accompanied with increased Faah expression. Main
      results indicated that FAAH inhibitor URB597 decreased neural proliferation, glia
      and apoptosis in a brain region-dependent manner, which were coupled to local
      changes in Faah and/or Cnr1 expression and a negative energy context. 

PMID- 25870541
TI  - Can intracellular cAMP dynamics enable scalable computation?

PMID- 25870540
TI  - Aged neuronal nitric oxide knockout mice show preserved olfactory learning in
      both social recognition and odor-conditioning tasks.
AB  - There is evidence for both neurotoxic and neuroprotective roles of nitric oxide
      (NO) in the brain and changes in the expression of the neuronal isoform of NO
      synthase (nNOS) gene occur during aging. The current studies have investigated
      potential support for either a neurotoxic or neuroprotective role of NO derived
      from nNOS in the context of aging by comparing olfactory learning and locomotor
      function in young compared to old nNOS knockout (nNOS(-/-)) and wildtype control
      mice. Tasks involving social recognition and olfactory conditioning paradigms
      showed that old nNOS(-/-) animals had improved retention of learning compared to
      similar aged wildtype controls. Young nNOS(-/-) animals showed superior reversal
      learning to wildtypes in a conditioned learning task, although their performance
      was weakened with age. Interestingly, whereas young nNOS(-/-) animals were
      impaired in long term memory for social odors compared to wildtype controls, in
      old animals this pattern was reversed, possibly indicating beneficial
      compensatory changes influencing olfactory memory may occur during aging in nNOS(
      /-) animals. Possibly such compensatory changes may have involved increased NO
      from other NOS isoforms since the memory deficit in young nNOS(-/-) animals could
      be rescued by the NO-donor, molsidomine. Both nNOS(-/-) and wildtype animals
      showed an age-associated decline in locomotor activity although young nNOS(-/-)
      animals were significantly more active than wildtypes, possibly due to an
      increased interest in novelty. Overall our findings suggest that lack of NO
      release via nNOS may protect animals to some extent against age-associated
      cognitive decline in memory tasks typically involving olfactory and hippocampal
      regions, but not against declines in reversal learning or locomotor activity. 

PMID- 25870538
TI  - MCPH1: a window into brain development and evolution.
AB  - The development of the mammalian cerebral cortex involves a series of mechanisms:
      from patterning, progenitor cell proliferation and differentiation, to neuronal
      migration. Many factors influence the development of the cerebral cortex to its
      normal size and neuronal composition. Of these, the mechanisms that influence the
      proliferation and differentiation of neural progenitor cells are of particular
      interest, as they may have the greatest consequence on brain size, not only
      during development but also in evolution. In this context, causative genes of
      human autosomal recessive primary microcephaly, such as ASPM and MCPH1, are
      attractive candidates, as many of them show positive selection during primate
      evolution. MCPH1 causes microcephaly in mice and humans and is involved in a
      diverse array of molecular functions beyond brain development, including DNA
      repair and chromosome condensation. Positive selection of MCPH1 in the primate
      lineage has led to much insight and discussion of its role in brain size
      evolution. In this review, we will present an overview of MCPH1 from these
      multiple angles, and whilst its specific role in brain size regulation during
      development and evolution remain elusive, the pieces of the puzzle will be
      discussed with the aim of putting together the full picture of this fascinating
      gene. 

PMID- 25870542
TI  - Whole-brain mapping of the direct inputs and axonal projections of POMC and AgRP
      neurons.
AB  - Pro-opiomelanocortin (POMC) neurons in the arcuate nucleus (ARC) of the
      hypothalamus and nucleus tractus solitarius (NTS) of the brainstem play important
      roles in suppressing food intake and maintaining energy homeostasis. Previous
      tract-tracing studies have revealed the axonal connection patterns of these two
      brain areas, but the intermingling of POMC neurons with other neuron types has
      made it challenging to precisely identify the inputs and outputs of POMC neurons.
      In this study, we used the modified rabies virus to map the brain areas that
      provide direct inputs to the POMC neurons in the ARC and NTS as well as the
      inputs to the ARC AgRP neurons for comparison. ARC POMC neurons receive inputs
      from dozens of discrete structures throughout the forebrain and brainstem. The
      brain areas containing the presynaptic partners of ARC POMC neurons largely
      overlap with those of ARC AgRP neurons, although POMC neurons receive relatively
      broader, denser inputs. Furthermore, POMC neurons in the NTS receive direct
      inputs predominantly from the brainstem and show very different innervation
      patterns for POMC neurons in the ARC. By selectively expressing fluorescent
      markers in the ARC and NTS POMC neurons, we found that almost all of their major
      presynaptic partners are innervated by POMC neurons in the two areas, suggesting
      that there are strong reciprocal projections among the major POMC neural
      pathways. By comprehensively chartering the whole-brain connections of the
      central melanocortin system in a cell-type-specific manner, this study lays the
      foundation for dissecting the roles and underlying circuit mechanisms of specific
      neural pathways in regulating energy homeostasis. 

PMID- 25870543
TI  - Direct electric stimulation to increase cerebrovascular function.

PMID- 25870545
TI  - Approaching motor and language deficits in autism from below: a biolinguistic
      perspective.

PMID- 25870544
TI  - The medial prefrontal cortex is crucial for the maintenance of persistent licking
      and the expression of incentive contrast.
AB  - We examined the role of the medial prefrontal cortex (mPFC) in reward processing
      and the control of consummatory behavior. Rats were trained in an operant licking
      procedure in which they received alternating access to solutions with relatively
      high and low levels of sucrose (20 and 4%, w/v). Each level of sucrose was
      available for fixed intervals of 30 s over 30 min test sessions. Over several
      days of training, rats came to lick persistently when the high level of sucrose
      was available and suppressed licking when the low level of sucrose was available.
      Pharmacological inactivations of the mPFC, specifically the rostral part of the
      prelimbic area, greatly reduced intake of the higher value fluid and only
      slightly increased intake of the lower value fluid. In addition, the
      inactivations altered within-session patterns and microstructural measures of
      licking. Rats licked equally for the high and low levels of sucrose at the
      beginning of the test sessions and "relearned" to reduce intake of the low value
      fluid over the test sessions. Durations of licking bouts (clusters of licks with
      inter-lick intervals <0.5 s) were reduced for the high value fluid and there were
      many more brief licking bouts (<1 s) when the low value fluid was available.
      These effects were verified using an alternative approach (optogenetic silencing
      using archaerhodopsin) and were distinct from inactivation of the ventral
      striatum, which simply increased overall intake. Our findings suggest that the
      mPFC is crucial for the maintenance of persistent licking and the expression of
      learned feeding strategies. 

PMID- 25870546
TI  - Deletion of mouse FXR gene disturbs multiple neurotransmitter systems and alters
      neurobehavior.
AB  - Farnesoid X receptor (FXR) is a nuclear hormone receptor involved in bile acid
      synthesis and homeostasis. Dysfunction of FXR is involved in cholestasis and
      atherosclerosis. FXR is prevalent in liver, gallbladder, and intestine, but it is
      not yet clear whether it modulates neurobehavior. In the current study, we tested
      the hypothesis that mouse FXR deficiency affects a specific subset of
      neurotransmitters and results in an unique behavioral phenotype. The FXR knockout
      mice showed less depressive-like and anxiety-related behavior, but increased
      motor activity. They had impaired memory and reduced motor coordination. There
      were changes of glutamatergic, GABAergic, serotoninergic, and norepinephrinergic
      neurotransmission in either hippocampus or cerebellum. FXR deletion decreased the
      amount of the GABA synthesis enzyme GAD65 in hippocampus but increased GABA
      transporter GAT1 in cerebral cortex. FXR deletion increased serum concentrations
      of many bile acids, including taurodehydrocholic acid, taurocholic acid,
      deoxycholic acid (DCA), glycocholic acid (GCA), tauro-alpha-muricholic acid,
      tauro-omega-muricholic acid, and hyodeoxycholic acid (HDCA). There were also
      changes in brain concentrations of taurocholic acid, taurodehydrocholic acid,
      tauro-omega-muricholic acid, tauro-beta-muricholic acid, deoxycholic acid, and
      lithocholic acid (LCA). Taken together, the results from studies with FXR
      knockout mice suggest that FXR contributes to the homeostasis of multiple
      neurotransmitter systems in different brain regions and modulates neurobehavior.
      The effect appears to be at least partially mediated by bile acids that are known
      to cross the blood-brain barrier (BBB) inducing potential neurotoxicity. 

PMID- 25870547
TI  - Conditional targeting of medium spiny neurons in the striatal matrix.
AB  - The striatum serves as the main input to the basal ganglia, and is key for the
      regulation of motor behaviors, compulsion, addiction, and various cognitive and
      emotional states. Its deterioration is associated with degenerative disorders
      such as Huntington's disease. Despite its apparent anatomical uniformity, it
      consists of intermingled cell populations, which have precluded straightforward
      anatomical sub-classifications adhering to functional dissections. Approximately
      95% of the striatal neurons are inhibitory projection neurons termed medium spiny
      neurons (MSNs). They are commonly classified according to their expression of
      either dopamine receptor D1 or D2, which also determines their axonal projection
      patterns constituting the direct and indirect pathway in the basal ganglia.
      Immunohistochemical patterns have further indicated compartmentalization of the
      striatum to the striosomes and the surrounding matrix, which integrate MSNs of
      both the D1 and D2 type. Here, we present a transgenic mouse line, Gpr101-Cre,
      with Cre recombinase activity localized to matrix D1 and D2 MSNs. Using two
      Gpr101-Cre founder lines with different degrees of expression in the striatum, we
      conditionally deleted the vesicular inhibitory amino acid transporter (VIAAT),
      responsible for storage of GABA and glycine in synaptic vesicles. Partial
      ablation of VIAAT (in ~36% of MSNs) resulted in elevated locomotor activity
      compared to control mice, when provoked with the monoamine reuptake inhibitor
      cocaine. Near complete targeting of matrix MSNs led to profoundly changed motor
      behaviors, which increased in severity as the mice aged. Moreover, these mice had
      exaggerated muscle rigidity, retarded growth, increased rate of spontaneous
      deaths, and defective memory. Therefore, our data provide a link between
      dysfunctional GABA signaling of matrix MSNs to specific behavioral alterations,
      which are similar to the symptoms of Huntington's disease. 

PMID- 25870548
TI  - Disease-specific monoclonal antibodies targeting glutamate decarboxylase impair
      GABAergic neurotransmission and affect motor learning and behavioral functions.
AB  - Autoantibodies to the smaller isoform of glutamate decarboxylase (GAD) can be
      found in patients with type 1 diabetes and a number of neurological disorders,
      including stiff-person syndrome, cerebellar ataxia and limbic encephalitis. The
      detection of disease-specific autoantibody epitopes led to the hypothesis that
      distinct GAD autoantibodies may elicit specific neurological phenotypes. We
      explored the in vitro/in vivo effects of well-characterized monoclonal GAD
      antibodies. We found that GAD autoantibodies present in patients with stiff
      person syndrome (n = 7) and cerebellar ataxia (n = 15) recognized an epitope
      distinct from that recognized by GAD autoantibodies present in patients with type
      1 diabetes mellitus (n = 10) or limbic encephalitis (n = 4). We demonstrated that
      the administration of a monoclonal GAD antibody representing this epitope
      specificity; (1) disrupted in vitro the association of GAD with gamma
      Aminobutyric acid containing synaptic vesicles; (2) depressed the inhibitory
      synaptic transmission in cerebellar slices with a gradual time course and a
      lasting suppressive effect; (3) significantly decreased conditioned eyelid
      responses evoked in mice, with no modification of learning curves in the
      classical eyeblink-conditioning task; (4) markedly impaired the facilitatory
      effect exerted by the premotor cortex over the motor cortex in a paired-pulse
      stimulation paradigm; and (5) induced decreased exploratory behavior and impaired
      locomotor function in rats. These findings support the specific targeting of GAD
      by its autoantibodies in the pathogenesis of stiff-person syndrome and cerebellar
      ataxia. Therapies of these disorders based on selective removal of such GAD
      antibodies could be envisioned. 

PMID- 25870549
TI  - How and why affective and reactive virtual agents will bring new insights on
      social cognitive disorders in schizophrenia? An illustration with a virtual card
      game paradigm.
AB  - In recent decades, many studies have shown that schizophrenia is associated with
      severe social cognitive impairments affecting key components, such as the
      recognition of emotions, theory of mind, attributional style, and metacognition.
      Most studies investigated each construct separately, precluding analysis of the
      interactive and immersive nature of real-life situation. Specialized batteries of
      tests are under investigation to assess social cognition, which is thought now as
      a link between neurocognitive disorders and impaired functioning. However, this
      link accounts for a limited part of the variance of real-life functioning. To
      fill this gap, advances in virtual reality and affective computing have made it
      possible to carry out experimental investigations of naturalistic social
      cognition, in controlled conditions, with good reproducibility. This approach is
      illustrated with the description of a new paradigm based on an original virtual
      card game in which subjects interpret emotional displays from a female virtual
      agent, and decipher her helping intentions. Independent variables concerning
      emotional expression in terms of valence and intensity were manipulated. We show
      how several useful dependant variables, ranging from classic experimental
      psychology data to metacognition or subjective experiences records, may be
      extracted from a single experiment. Methodological issues about the immersion
      into a simulated intersubjective situation are considered. The example of this
      new flexible experimental setting, with regards to the many constructs recognized
      in social neurosciences, constitutes a rationale for focusing on this potential
      intermediate link between standardized tests and real-life functioning, and also
      for using it as an innovative media for cognitive remediation. 

PMID- 25870550
TI  - Are treatment effects of neurofeedback training in children with ADHD related to
      the successful regulation of brain activity? A review on the learning of
      regulation of brain activity and a contribution to the discussion on specificity.
AB  - While issues of efficacy and specificity are crucial for the future of
      neurofeedback training, there may be alternative designs and control analyses to
      circumvent the methodological and ethical problems associated with double-blind
      placebo studies. Surprisingly, most NF studies do not report the most immediate
      result of their NF training, i.e., whether or not children with ADHD gain control
      over their brain activity during the training sessions. For the investigation of
      specificity, however, it seems essential to analyze the learning and adaptation
      processes that take place in the course of the training and to relate
      improvements in self-regulated brain activity across training sessions to
      behavioral, neuropsychological and electrophysiological outcomes. To this aim, a
      review of studies on neurofeedback training with ADHD patients which include the
      analysis of learning across training sessions or relate training performance to
      outcome is presented. Methods on how to evaluate and quantify learning of EEG
      regulation over time are discussed. "Non-learning" has been reported in a small
      number of ADHD-studies, but has not been a focus of general methodological
      discussion so far. For this reason, selected results from the brain-computer
      interface (BCI) research on the so-called "brain-computer illiteracy", the
      inability to gain control over one's brain activity, are also included. It is
      concluded that in the discussion on specificity, more attention should be devoted
      to the analysis of EEG regulation performance in the course of the training and
      its impact on clinical outcome. It is necessary to improve the knowledge on
      characteristic cross-session and within-session learning trajectories in ADHD and
      to provide the best conditions for learning. 

PMID- 25870551
TI  - Seeing the world through non rose-colored glasses: anxiety and the amygdala
      response to blended expressions.
AB  - Anxious individuals have a greater tendency to categorize faces with ambiguous
      emotional expressions as fearful (Richards et al., 2002). These behavioral
      findings might reflect anxiety-related biases in stimulus representation within
      the human amygdala. Here, we used functional magnetic resonance imaging (fMRI)
      together with a continuous adaptation design to investigate the representation of
      faces from three expression continua (surprise-fear, sadness-fear, and surprise
      sadness) within the amygdala and other brain regions implicated in face
      processing. Fifty-four healthy adult participants completed a face expression
      categorization task. Nineteen of these participants also viewed the same
      expressions presented using type 1 index 1 sequences while fMRI data were
      acquired. Behavioral analyses revealed an anxiety-related categorization bias in
      the surprise-fear continuum alone. Here, elevated anxiety was associated with a
      more rapid transition from surprise to fear responses as a function of percentage
      fear in the face presented, leading to increased fear categorizations for faces
      with a mid-way blend of surprise and fear. fMRI analyses revealed that high trait
      anxious participants also showed greater representational similarity, as indexed
      by greater adaptation of the Blood Oxygenation Level Dependent (BOLD) signal,
      between 50/50 surprise/fear expression blends and faces from the fear end of the
      surprise-fear continuum in both the right amygdala and right fusiform face area
      (FFA). No equivalent biases were observed for the other expression continua.
      These findings suggest that anxiety-related biases in the processing of
      expressions intermediate between surprise and fear may be linked to differential
      representation of these stimuli in the amygdala and FFA. The absence of anxiety
      related biases for the sad-fear continuum might reflect intermediate expressions
      from the surprise-fear continuum being most ambiguous in threat-relevance. 

PMID- 25870552
TI  - Functional MRI neurofeedback training on connectivity between two regions induces
      long-lasting changes in intrinsic functional network.
AB  - Motor or perceptual learning is known to influence functional connectivity
      between brain regions and induce short-term changes in the intrinsic functional
      networks revealed as correlations in slow blood-oxygen-level dependent (BOLD)
      signal fluctuations. However, no cause-and-effect relationship has been
      elucidated between a specific change in connectivity and a long-term change in
      global networks. Here, we examine the hypothesis that functional connectivity
      (i.e., temporal correlation between two regions) is increased and preserved for a
      long time when two regions are simultaneously activated or deactivated. Using the
      connectivity-neurofeedback training paradigm, subjects successfully learned to
      increase the correlation of activity between the lateral parietal and primary
      motor areas, regions that belong to different intrinsic networks and negatively
      correlated before training under the resting conditions. Furthermore, whole-brain
      hypothesis-free analysis as well as functional network analyses demonstrated that
      the correlation in the resting state between these areas as well as the
      correlation between the intrinsic networks that include the areas increased for
      at least 2 months. These findings indicate that the connectivity-neurofeedback
      training can cause long-term changes in intrinsic connectivity and that intrinsic
      networks can be shaped by experience-driven modulation of regional correlation. 

PMID- 25870553
TI  - Sinistrals are rarely "right": evidence from tool-affordance processing in visual
      half-field paradigms.
AB  - Although current neuroscience and behavioral studies provide substantial
      understanding of tool representations (e.g., the processing of tool-related
      affordances) in the human brain, most of this knowledge is limited to right
      handed individuals with typical organization of cognitive and manual skills.
      Therefore, any insights from these lines of research may be of little value in
      rehabilitation of patients with atypical laterality of praxis and/or hand
      dominance. To fill this gap, we tested perceptual processing of man-made objects
      in 18 healthy left-handers who were likely to show greater incidence of right
      sided or bilateral (atypical) lateralization of functions. In the two experiments
      reported here, participants performed a tool vs. non-tool categorization task. In
      Experiment 1, target and distracter objects were presented for 200 ms in the left
      (LVF) or right (RVF) visual field, followed by 200 ms masks. In Experiment 2, the
      centrally presented targets were preceded by masked primes of 35 ms duration,
      again presented in the LVF or RVF. Based on results from both studies, i.e.,
      response times (RTs) to correctly discriminated stimuli irrespective of their
      category, participants were divided into two groups showing privileged processing
      in either left (N = 9) or right (N = 9) visual field. In Experiment 1, only
      individuals with RVF advantage showed significantly faster categorization of
      tools in their dominant visual field, whereas those with LVF advantage revealed
      merely a trend toward such an effect. In Experiment 2, when targets were preceded
      by identical primes, the "atypical" group showed significantly facilitated
      categorization of non-tools, whereas the "typical" group demonstrated a trend
      toward faster categorization of tools. These results indicate that in subjects
      with atypically organized cognitive skills, tool-related processes are not just
      mirror reversed. Thus, our outcomes call for particular caution in
      neurorehabilitation directed at left-handed individuals. 

PMID- 25870554
TI  - A Single-Session Preliminary Evaluation of an Affordable BCI-Controlled Arm
      Exoskeleton and Motor-Proprioception Platform.
AB  - Traditional, hospital-based stroke rehabilitation can be labor-intensive and
      expensive. Furthermore, outcomes from rehabilitation are inconsistent across
      individuals and recovery is hard to predict. Given these uncertainties, numerous
      technological approaches have been tested in an effort to improve rehabilitation
      outcomes and reduce the cost of stroke rehabilitation. These techniques include
      brain-computer interface (BCI), robotic exoskeletons, functional electrical
      stimulation (FES), and proprioceptive feedback. However, to the best of our
      knowledge, no studies have combined all these approaches into a rehabilitation
      platform that facilitates goal-directed motor movements. Therefore, in this
      paper, we combined all these technologies to test the feasibility of using a BCI
      driven exoskeleton with FES (robotic training device) to facilitate motor task
      completion among individuals with stroke. The robotic training device operated to
      assist a pre-defined goal-directed motor task. Because it is hard to predict who
      can utilize this type of technology, we considered whether the ability to adapt
      skilled movements with proprioceptive feedback would predict who could learn to
      control a BCI-driven robotic device. To accomplish this aim, we developed a motor
      task that requires proprioception for completion to assess motor-proprioception
      ability. Next, we tested the feasibility of robotic training system in
      individuals with chronic stroke (n = 9) and found that the training device was
      well tolerated by all the participants. Ability on the motor-proprioception task
      did not predict the time to completion of the BCI-driven task. Both participants
      who could accurately target (n = 6) and those who could not (n = 3), were able to
      learn to control the BCI device, with each BCI trial lasting on average 2.47 min.
      Our results showed that the participants' ability to use proprioception to
      control motor output did not affect their ability to use the BCI-driven
      exoskeleton with FES. Based on our preliminary results, we show that our robotic
      training device has potential for use as therapy for a broad range of individuals
      with stroke. 

PMID- 25870555
TI  - Bimanual elbow robotic orthoses: preliminary investigations on an impairment
      force-feedback rehabilitation method.
AB  - Modern rehabilitation practices have begun integrating robots, recognizing their
      significant role in recovery. New and alternative stroke rehabilitation
      treatments are essential to enhance efficacy and mitigate associated health
      costs. Today's robotic interventions can play a significant role in advancing
      rehabilitation. In addition, robots have an inherent ability to perform tasks
      accurately and reliably and are typically well suited to measure and quantify
      performance. Most rehabilitation strategies predominantly target activation of
      the paretic arm. However, bimanual upper-limb rehabilitation research suggests
      potential in enhancing functional recovery. Moreover, studies suggest that limb
      coordination and synchronization can improve treatment efficacy. In this
      preliminary study, we aimed to investigate and validate our user-driven bimanual
      system in a reduced intensity rehab practice. A bimanual wearable robotic device
      (BWRD) with a Master-Slave configuration for the elbow joint was developed to
      carry out the investigation. The BWRD incorporates position and force sensors for
      which respective control loops are implemented, and offers varying modes of
      operation ranging from passive to active training. The proposed system enables
      the perception of the movements, as well as the forces applied by the hemiparetic
      arm, with the non-hemiparetic arm. Eight participants with chronic unilateral
      stroke were recruited to participate in a total of three 1-h sessions per
      participant, delivered in a week. Participants underwent pre- and post-training
      functional assessments along with proprioceptive measures. The post-assessment
      was performed at the end of the last training session. The protocol was designed
      to engage the user in an assortment of static and dynamic arm matching and
      opposing tasks. The training incorporates force-feedback movements, force
      feedback positioning, and force matching tasks with same and opposite direction
      movements. We are able to suggest identification of impairment patterns in the
      position-force plot results. In addition, we performed a proprioception
      evaluation with the system. We set out to design innovative and user immersive
      training tasks that utilize the BWRD capabilities, and we demonstrate that the
      subjects were able to cooperate and accomplish the protocol. We found that the
      Fugl-Meyer and Wolf Motor Function Test (pre to post) measured improvements (15
      and 19%, respectively). Recognizing the brevity of the training, we focus our
      report primarily on the proprioception testing (32% significant improvement, p
      prop = 0.033) and protocol distinctive features and results. This paper presents
      the electromechanical features and performance of the BWRD, the testing protocol,
      and the assessments utilized. Outcome measures and results are presented and
      demonstrate the successful application and operation of the system. 

PMID- 25870556
TI  - Atypical coordination of cortical oscillations in response to speech in autism.
AB  - Subjects with autism often show language difficulties, but it is unclear how they
      relate to neurophysiological anomalies of cortical speech processing. We used
      combined EEG and fMRI in 13 subjects with autism and 13 control participants and
      show that in autism, gamma and theta cortical activity do not engage
      synergistically in response to speech. Theta activity in left auditory cortex
      fails to track speech modulations, and to down-regulate gamma oscillations in the
      group with autism. This deficit predicts the severity of both verbal impairment
      and autism symptoms in the affected sample. Finally, we found that oscillation
      based connectivity between auditory and other language cortices is altered in
      autism. These results suggest that the verbal disorder in autism could be
      associated with an altered balance of slow and fast auditory oscillations, and
      that this anomaly could compromise the mapping between sensory input and higher
      level cognitive representations. 

PMID- 25870558
TI  - Mechanisms underlying firing in healthy and sick human motoneurons.

PMID- 25870557
TI  - Functional organization and restoration of the brain motor-execution network
      after stroke and rehabilitation.
AB  - Multiple cortical areas of the human brain motor system interact coherently in
      the low frequency range (<0.1 Hz), even in the absence of explicit tasks.
      Following stroke, cortical interactions are functionally disturbed. How these
      interactions are affected and how the functional organization is regained from
      rehabilitative treatments as people begin to recover motor behaviors has not been
      systematically studied. We recorded the intrinsic functional magnetic resonance
      imaging (fMRI) signals from 30 participants: 17 young healthy controls and 13
      aged stroke survivors. Stroke participants underwent mental practice (MP) or both
      mental practice and physical therapy (MP+PT) within 14-51 days following stroke.
      We investigated the network activity of five core areas in the motor-execution
      network, consisting of the left primary motor area (LM1), the right primary motor
      area (RM1), the left pre-motor cortex (LPMC), the right pre-motor cortex (RPMC)
      and the supplementary motor area (SMA). We discovered that (i) the network
      activity dominated in the frequency range 0.06-0.08 Hz for all the regions, and
      for both able-bodied and stroke participants (ii) the causal information flow
      between the regions: LM1 and SMA, RPMC and SMA, RPMC and LM1, SMA and RM1, SMA
      and LPMC, was reduced significantly for stroke survivors (iii) the flow did not
      increase significantly after MP alone and (iv) the flow among the regions during
      MP+PT increased significantly. We also found that sensation and motor scores were
      significantly higher and correlated with directed functional connectivity
      measures when the stroke-survivors underwent MP+PT but not MP alone. The findings
      provide evidence that a combination of mental practice and physical therapy can
      be an effective means of treatment for stroke survivors to recover or regain the
      strength of motor behaviors, and that the spectra of causal information flow can
      be used as a reliable biomarker for evaluating rehabilitation in stroke
      survivors. 

PMID- 25870559
TI  - ER proteostasis disturbances in Parkinson's disease: novel insights.

PMID- 25870560
TI  - Aging impairs deliberation and behavioral flexibility in inter-temporal choice.
AB  - Inter-temporal choice depends on multiple, interacting systems, some of which may
      be compromised with age. Some of these systems may be responsible for ongoing
      trial-by-trial choice strategies. Some may represent the consequences of action.
      Some may be necessary for the coupling between anticipated consequences and
      strategies currently in use, flexibly guiding behavior. When faced with a
      difficult decision, rats will orient back and forth, a behavior termed "vicarious
      trial and error" (VTE). Recent experiments have linked the occurrence of VTE to
      hippocampal search processes and behavioral flexibility. We tested 5 month (n =
      6), 9 month (n = 8) and over-27 month-old (n = 10) rats on a Spatial Adjusting
      Delay Discounting task to examine how aging impacted lap-by-lap strategies and
      VTE during inter-temporal choice. Rats chose between spatially separated food
      goals that provided a smaller-sooner or larger-later reward. On each lap, the
      delay to the larger-later reward was adjusted as a function of the rat's
      decisions, increasing by 1 s after delayed-side choices and decreasing by 1 s
      after non-delayed side choices. The strategies that aged rats used differed from
      those used in young and adult rats. Moreover, aged rats produced reliably more
      VTE behaviors, for protracted periods of time, uncoupled from behavioral
      flexibility. 

PMID- 25870561
TI  - Herbal medicine IMOD suppresses LPS-induced production of proinflammatory
      cytokines in human dendritic cells.
AB  - Traditional medicines that stimulate or modulate the immune system can be used as
      innovative approaches to treat immunological diseases. The herbal medicine IMOD
      has been shown to strongly modulate immune responses in several animal studies as
      well as in clinical trials. However, little is known about the mechanisms of IMOD
      to modulate immunity. Here we have investigated whether IMOD modulates the
      immunological function of human dendritic cells (DCs). IMOD alone did not induce
      DC maturation nor production of cytokines. Notably, IMOD decreased the production
      of pro-inflammatory cytokines IL-6, IL-12 p70, and TNFalpha by LPS-activated DCs
      at both mRNA and protein levels in a dose dependent manner. In contrast,
      treatment with IMOD did not affect LPS induced-production of the anti
      inflammatory cytokine IL-10. Furthermore, IMOD inhibited T cell
      activation/proliferation by LPS-treated DCs and skewed T-cells responses toward
      the T helper type 2 polarization. These data strongly indicate that IMOD has a
      potent immunomodulatory ability that affects TLR signaling and thereby modulates
      DC function. Insight into the immunomodulatory effect of herbal medicine IMOD may
      provide innovative strategies to affect the immune system and to help combat
      various diseases. 

PMID- 25870563
TI  - Complex nonlinear autonomic nervous system modulation link cardiac autonomic
      neuropathy and peripheral vascular disease.
AB  - BACKGROUND: Physiological interactions are abundant within, and between, body
      systems. These interactions may evolve into discrete states during
      pathophysiological processes resulting from common mechanisms. An association
      between arterial stenosis, identified by low ankle-brachial pressure index (ABPI)
      and cardiovascular disease (CVD) as been reported. Whether an association between
      vascular calcification-characterized by high ABPI and a different pathophysiology
      is similarly associated with CVD, has not been established. The current study
      aims to investigate the association between ABPI, and cardiac rhythm, as an
      indicator of cardiovascular health and functionality, utilizing heart rate
      variability (HRV). METHODS AND RESULTS: Two hundred and thirty six patients
      underwent ABPI assessment. Standard time and frequency domain, and non-linear HRV
      measures were determined from 5-min electrocardiogram. ABPI data were divided
      into normal (n = 101), low (n = 67) and high (n = 66) and compared to HRV
      measures.(DFAalpha1 and SampEn were significantly different between the low ABPI,
      high ABPI and control groups (p < 0.05). CONCLUSION: A possible coupling between
      arterial stenosis and vascular calcification with decreased and increased HRV
      respectively was observed. Our results suggest a model for interpreting the
      relationship between vascular pathophysiology and cardiac rhythm. The
      cardiovascular system may be viewed as a complex system comprising a number of
      interacting subsystems. These cardiac and vascular subsystems/networks may be
      coupled and undergo transitions in response to internal or external
      perturbations. From a clinical perspective, the significantly increased sample
      entropy compared to the normal ABPI group and the decreased and increased complex
      correlation properties measured by DFA for the low and high ABPI groups
      respectively, may be useful indicators that a more holistic treatment approach in
      line with this more complex clinical picture is required.

PMID- 25870562
TI  - Detecting and monitoring arrhythmia recurrence following catheter ablation of
      atrial fibrillation.
AB  - Atrial fibrillation (AF) is the most common arrhythmia prompting clinical
      presentation, is associated with significant morbidity and mortality. The
      incidence and prevalence of this arrhythmia is expected to grow significantly in
      the coming decades. Of the available pharmacologic and non-pharmacologic
      treatment options, the fastest growing and most intensely studied is catheter
      based ablation therapy for AF. Given the varying success rates for AF ablation,
      the increasingly complex factors that need to be taken into account when deciding
      to proceed with ablation, as well as varying definitions of procedural success,
      accurate detection of arrhythmia recurrence and its burden is of significance.
      Detecting and monitoring AF recurrence following catheter ablation is therefore
      an important consideration. Multiple studies have demonstrated the close
      relationship between the intensity of rhythm monitoring with wearable ambulatory
      cardiac monitors, or implantable cardiac rhythm monitors and the detection of
      arrhythmia recurrence. Other studies have employed algorithms dependent on
      intensive monitoring and arrhythmia detection in the decision tree on whether to
      proceed with repeat ablation or medical therapy. In this review, we discuss these
      considerations, types of monitoring devices, and implications for monitoring AF
      recurrence following catheter ablation. 

PMID- 25870564
TI  - Uremic myopathy: is oxidative stress implicated in muscle dysfunction in uremia?
AB  - Renal failure is accompanied by progressive muscle weakness and premature
      fatigue, in part linked to hypokinesis and in part to uremic toxicity. These
      changes are associated with various detrimental biochemical and morphological
      alterations. All of these pathological parameters are collectively termed uremic
      myopathy. Various interventions while helpful can't fully remedy the pathological
      phenotype. Complex mechanisms that stimulate muscle dysfunction in uremia have
      been proposed, and oxidative stress could be implicated. Skeletal muscles
      continuously produce reactive oxygen species (ROS) and reactive nitrogen species
      (RNS) at rest and more so during contraction. The aim of this mini review is to
      provide an update on recent advances in our understanding of how ROS and RNS
      generation might contribute to muscle dysfunction in uremia. Thus, a systematic
      review was conducted searching PubMed and Scopus by using the Cochrane and PRISMA
      guidelines. While few studies met our criteria their findings are discussed
      making reference to other available literature data. Oxidative stress can direct
      muscle cells into a catabolic state and chronic exposure to it leads to wasting.
      Moreover, redox disturbances can significantly affect force production per se. We
      conclude that oxidative stress can be in part responsible for some aspects of
      uremic myopathy. Further research is needed to discern clear mechanisms and to
      help efforts to counteract muscle weakness and exercise intolerance in uremic
      patients. 

PMID- 25870566
TI  - Measuring patient engagement: development and psychometric properties of the
      Patient Health Engagement (PHE) Scale.
AB  - Beyond the rhetorical call for increasing patients' engagement, policy makers
      recognize the urgency to have an evidence-based measure of patients' engagement
      and capture its effect when planning and implementing initiatives aimed at
      sustaining the engagement of consumers in their health. In this paper, authors
      describe the Patient Health Engagement Scale (PHE-scale), a measure of patient
      engagement that is grounded in rigorous conceptualization and appropriate
      psychometric methods. The scale was developed based on our previous
      conceptualization of patient engagement (the PHE-model). In particular, the items
      of the PHE-scale were developed based on the findings from the literature review
      and from interviews with chronic patients. Initial psychometric analysis was
      performed to pilot test a preliminary version of the items. The items were then
      refined and administered to a national sample of chronic patients (N = 382) to
      assess the measure's psychometric performance. A final phase of test-retest
      reliability was performed. The analysis showed that the PHE Scale has good
      psychometric properties with good correlation with concurrent measures and solid
      reliability. Having a valid and reliable measure to assess patient engagement is
      the first step in understanding patient engagement and its role in health care
      quality, outcomes, and cost containment. The PHE Scale shows a promising clinical
      relevance, indicating that it can be used to tailor intervention and assess
      changes after patient engagement interventions. 

PMID- 25870567
TI  - A new visualization and conceptualization of categorical longitudinal
      development: measurement invariance and change.
AB  - The Overlapping Waves Model (OWM) is a metaphor introduced by Siegler (1996) to
      illustrate a typical sequence of increasing and decreasing use of strategies
      during development. Going beyond metaphor, a new model synthesized from Latent
      Growth Modeling (LGM) and Item Response Theory (IRT) will be presented to analyze
      such categorical longitudinal data. Use of strategies can be scored as a variable
      with only a few ordinal categories. IRT provides the means to relate the usage of
      strategies to position on an underlying developmental dimension. LGM allows to
      model movement of individuals along this dimension, acknowledging individual
      differences both in starting point and in speed of progress. Measuring and
      modeling such strategy development requires that at each time point the same
      categories are used, in the sense that item difficulties must remain invariant
      over time. Whether, discrimination can be relaxed is still an issue. The problem
      that had to be solved was disentangling the between-person-individual differences
      from real intra-individual developmental differences. Figures with polytomous or
      multi-category Item Characteristic Curves (ICC's) resemble the OWM in many
      respects. However, such figures are usually taken to represent inter-individual
      differences, whereas the OWM usually represents development (so intra-individual
      differences), and we cannot have both at the same time. The solution came from
      creating a framework with ability differences on one axis and the effect of time
      on another axis, resulting in a 3-D model. These (orthogonal) dimensions make it
      possible to adequately conceptualize measurement invariance in this complex
      context. As the result is difficult to conceptualize without extensive
      visualization, special 3-D figures will be used to illustrate and a dynamic
      (rotatable and scalable) version will be made available as Computable Document
      Format object (Mathematica). The model was successfully applied in several
      microgenetic studies. 

PMID- 25870565
TI  - Childhood Maltreatment, Depression, and Suicidal Ideation: Critical Importance of
      Parental and Peer Emotional Abuse during Developmental Sensitive Periods in Males
      and Females.
AB  - BACKGROUND: The adverse childhood experience (ACE) study found that risk for
      depression increased as a function of number of types of childhood maltreatment,
      and interpret this as a result of cumulative stress. An alternative hypothesis is
      that risk depends on type and timing of maltreatment. This will also present as a
      linear increase, since exposure to more types of abuse increases likelihood of
      experiencing a critical type of abuse at a critical age. METHODS: 560 (223M/337F)
      young adults (18-25 years) were recruited from the community without regard to
      diagnosis and balanced to have equal exposure to 0-4 plus types of maltreatment.
      The Maltreatment and Abuse Chronology of Exposure Scale assessed severity of
      exposure to 10 types of maltreatment across each year of childhood. Major
      depressive disorder (MDD) and current symptoms were evaluated by SCID, interview,
      and self-report. Predictive analytics assessed importance of exposure at each age
      and evaluated whether exposure at one or two ages was a more important predictor
      than number, severity, or duration of maltreatment across childhood. RESULTS: The
      most important predictors of lifetime history of MDD were non-verbal emotional
      abuse in males and peer emotional abuse (EA) in females at 14 years of age, and
      these were more important predictors across models than number of types of
      maltreatment (males: t 9 = 16.39, p < 10(-7); females t 9 = 5.78, p < 10(-4)).
      Suicidal ideation was predicted, in part, by NVEA and peer EA at age 14, but most
      importantly by parental verbal abuse at age 5 in males and sexual abuse at age 18
      in females. CONCLUSION: This study provides evidence for sensitive exposure
      periods when maltreatment maximally impacts risk for depression, and provides an
      alternative interpretation of the ACE study results. These findings fit with
      emerging neuroimaging evidence for regional sensitivity periods. The presence of
      sensitive exposure periods has important implications for prevention, preemption,
      and treatment of MDD.

PMID- 25870569
TI  - Rehearsal development as development of iterative recall processes.
AB  - Although much is known about the critical importance of active verbal rehearsal
      for successful recall, knowledge about the mechanisms of rehearsal and their
      respective development in children is very limited. To be able to rehearse
      several items together, these items have to be available, or, if presented and
      rehearsed previously, retrieved from memory. Therefore, joint rehearsal of
      several items may itself be considered recall. Accordingly, by analyzing free
      recall, one cannot only gain insight into how recall and rehearsal unfold, but
      also into how principles that govern children's recall govern children's
      rehearsal. Over a period of three and a half years (beginning at grade 3) 54
      children were longitudinally assessed seven times on several overt rehearsal free
      recall trials. A first set of analyses on recall revealed significant age-related
      increases in the primacy effect and an age-invariant recency effect. In the
      middle portion of the list, wave-shaped recall characteristics emerged and
      increased with age, indicating grouping of the list into subsequences. In a
      second set of analyses, overt rehearsal behavior was decomposed into distinct
      rehearsal sets. Analyses of these sets revealed that the distribution of
      rehearsals within each set resembled the serial position curves with one- or two
      item primacy and recency effects and wave-shaped rehearsal patterns in between.
      In addition, rehearsal behavior throughout the list was characterized by a
      decreasing tendency to begin rehearsal sets with the first list item. This result
      parallels the phenomenon of beginning recall with the first item on short lists
      and with the last item on longer lists. 

PMID- 25870568
TI  - Searching for flavor labels in food products: the influence of color-flavor
      congruence and association strength.
AB  - Prior research provides robust support for the existence of a number of
      associations between colors and flavors. In the present study, we examined
      whether congruent (vs. incongruent) combinations of product packaging colors and
      flavor labels would facilitate visual search for products labeled with specific
      flavors. The two experiments reported here document a Stroop-like effect between
      flavor words and packaging colors. The participants were able to search for
      packaging flavor labels more rapidly when the color of the packaging was
      congruent with the flavor label (e.g., red/tomato) than when it was incongruent
      (e.g., yellow/tomato). In addition, when the packaging color was incongruent,
      those flavor labels that were more strongly associated with a specific color
      yielded slower reaction times and more errors (Stroop interference) than those
      that were less strongly tied to a specific color. Importantly, search efficiency
      was affected both by color/flavor congruence and association strength. Taken
      together, these results therefore highlight the role of color congruence and
      color-word association strength when it comes to searching for specific flavor
      labels. 

PMID- 25870570
TI  - The hidden opportunity cost of time effect on intertemporal choice.
AB  - An interesting phenomenon called "hidden opportunity cost of time effect" was
      detected in intertemporal choices. The majority of our participants preferred the
      smaller but sooner (SS) option to the larger but later (LL) option if opportunity
      cost was explicit. However, a higher proportion of participants preferred the LL
      to SS option if opportunity cost was hidden. This shift violates the invariance
      principle and opens a new way to encourage future-oriented behavior. By simply
      mentioning the "obvious" opportunity cost of alternatives, decision makers can be
      more informed in prioritizing their long-term goals rather than short-term goals.

PMID- 25870571
TI  - Control over the strength of connections between modules: a double dissociation
      between stimulus format and task revealed by Granger causality mapping in fMRI.
AB  - Drawing on theoretical and computational work with the localist dual route
      reading model and results from behavioral studies, Besner et al. (2011) proposed
      that the ability to perform tasks that require overriding stimulus-specific
      defaults (e.g., semantics when naming Arabic numerals, and phonology when
      evaluating the parity of number words) necessitate the ability to modulate the
      strength of connections between cognitive modules for lexical representation,
      semantics, and phonology on a task- and stimulus-specific basis. We used
      functional magnetic resonance imaging to evaluate this account by assessing
      changes in functional connectivity while participants performed tasks that did
      and did not require such stimulus-task default overrides. The occipital region
      showing the greatest modulation of BOLD signal strength for the two stimulus
      types was used as the seed region for Granger causality mapping (GCM). Our GCM
      analysis revealed a region of rostromedial frontal cortex with a crossover
      interaction. When participants performed tasks that required overriding stimulus
      type defaults (i.e., parity judgments of number words and naming Arabic numerals)
      functional connectivity between the occipital region and rostromedial frontal
      cortex was present. Statistically significant functional connectivity was absent
      when the tasks were the default for the stimulus type (i.e., parity judgments of
      Arabic numerals and reading number words). This frontal region (BA 10) has
      previously been shown to be involved in goal-directed behavior and maintenance of
      a specific task set. We conclude that overriding stimulus-task defaults requires
      a modulation of connection strengths between cognitive modules and that the
      override mechanism predicted from cognitive theory is instantiated by frontal
      modulation of neural activity of brain regions specialized for sensory
      processing. 

PMID- 25870572
TI  - What's really wrong with cognitive behavioral therapy for psychosis?

PMID- 25870573
TI  - She called that thing a mido, but should you call it a mido too? Linguistic
      experience influences infants' expectations of conventionality.
AB  - Words are powerful communicative tools because of conventionality-their meanings
      are shared among same language users. Although evidence demonstrates that an
      understanding of conventionality is present early in life, this work has focused
      on infants being raised in English-speaking monolingual environments. As such,
      little is known about the role that experience in multilingual environments plays
      in the development of an understanding of conventionality. We addressed this gap
      with 13-month-old infants regularly exposed to more than one language. Infants
      were familiarized to two speakers who either spoke the same (English), or
      different (French vs. English) languages. Next, infants were habituated to a
      video in which one of the speakers provided a new word and selected one of two
      unfamiliar objects. Infants were then shown test events in which the other
      speaker provided the same label and selected either the same object or a
      different object. Our results demonstrate that exposure to at least one other
      language influences infants' expectations about conventionality. Unlike
      monolinguals, bilingual infants do not assume that word meanings are shared
      across speakers who use the same language. Interestingly, when shown speakers who
      use different languages, bilingual infants looked longer toward the test trials
      in which the second speaker labeled the object consistently with the first
      speaker. This finding suggests that exposure to multiple languages enhances
      infants' understanding that speakers who use different languages should not use
      the same word for the same object. This is the first known evidence that
      experience in multilingual environments influences infants' expectations
      surrounding the shared nature of word meanings. An increased sensitivity to the
      constraints of conventionality represents a fairly sophisticated understanding of
      language as a conventional system and may shape bilingual infants' language
      development in a number of important ways. 

PMID- 25870574
TI  - Eighty phenomena about the self: representation, evaluation, regulation, and
      change.
AB  - We propose a new approach for examining self-related aspects and phenomena. The
      approach includes (1) a taxonomy and (2) an emphasis on multiple levels of
      mechanisms. The taxonomy categorizes approximately eighty self-related phenomena
      according to three primary functions involving the self: representing, effecting,
      and changing. The representing self encompasses the ways in which people depict
      themselves, either to themselves or to others (e.g., self-concepts, self
      presentation). The effecting self concerns ways in which people facilitate or
      limit their own traits and behaviors (e.g., self-enhancement, self-regulation).
      The changing self is less time-limited than the effecting self; it concerns
      phenomena that involve lasting alterations in how people represent and control
      themselves (e.g., self-expansion, self-development). Each self-related phenomenon
      within these three categories may be examined at four levels of interacting
      mechanisms (social, individual, neural, and molecular). We illustrate our
      approach by focusing on seven self-related phenomena. 

PMID- 25870575
TI  - Assessing cognitive processes with diffusion model analyses: a tutorial based on
      fast-dm-30.
AB  - Diffusion models can be used to infer cognitive processes involved in fast binary
      decision tasks. The model assumes that information is accumulated continuously
      until one of two thresholds is hit. In the analysis, response time distributions
      from numerous trials of the decision task are used to estimate a set of
      parameters mapping distinct cognitive processes. In recent years, diffusion model
      analyses have become more and more popular in different fields of psychology.
      This increased popularity is based on the recent development of several software
      solutions for the parameter estimation. Although these programs make the
      application of the model relatively easy, there is a shortage of knowledge about
      different steps of a state-of-the-art diffusion model study. In this paper, we
      give a concise tutorial on diffusion modeling, and we present fast-dm-30, a
      thoroughly revised and extended version of the fast-dm software (Voss and Voss,
      2007) for diffusion model data analysis. The most important improvement of the
      fast-dm version is the possibility to choose between different optimization
      criteria (i.e., Maximum Likelihood, Chi-Square, and Kolmogorov-Smirnov), which
      differ in applicability for different data sets. 

PMID- 25870576
TI  - Music as a manifestation of life: exploring enactivism and the 'eastern
      perspective' for music education.
AB  - The enactive approach to cognition is developed in the context of music and music
      education. I discuss how this embodied point of view affords a relational and bio
      cultural perspective on music that decentres the Western focus on language,
      symbol and representation as the fundamental arbiters of meaning. I then explore
      how this 'life-based' approach to cognition and meaning-making offers a welcome
      alternative to standard Western academic approaches to music education. More
      specifically, I consider how the enactive perspective may aid in developing
      deeper ecological understandings of the transformative, extended and
      interpenetrative nature of the embodied musical mind; and thus help (re)connect
      students and teachers to the lived experience of their own learning and teaching.
      Following this, I examine related concepts associated with Buddhist psychology in
      order to develop possibilities for a contemplative music pedagogy. To conclude, I
      consider how an enactive-contemplative perspective may help students and teachers
      awaken to the possibilities of music education as 'ontological education.' That
      is, through a deeper understanding of 'music as a manifestation of life'
      rediscover their primordial nature as autopoietic and world-making creatures and
      thus engage more deeply with musicality as a means of forming richer and more
      compassionate relationships with their peers, their communities and the 'natural'
      and cultural worlds they inhabit. 

PMID- 25870577
TI  - The way you say it, the way I feel it: emotional word processing in accented
      speech.
AB  - The present study examined whether processing words with affective connotations
      in a listener's native language may be modulated by accented speech. To address
      this question, we used the Event Related Potential (ERP) technique and recorded
      the cerebral activity of Spanish native listeners, who performed a semantic
      categorization task, while listening to positive, negative and neutral words
      produced in standard Spanish or in four foreign accents. The behavioral results
      yielded longer latencies for emotional than for neutral words in both native and
      foreign-accented speech, with no difference between positive and negative words.
      The electrophysiological results replicated previous findings from the emotional
      language literature, with the amplitude of the Late Positive Complex (LPC),
      associated with emotional language processing, being larger (more positive) for
      emotional than for neutral words at posterior scalp sites. Interestingly, foreign
      accented speech was found to interfere with the processing of positive valence
      and go along with a negativity bias, possibly suggesting heightened attention to
      negative words. The manipulation employed in the present study provides an
      interesting perspective on the effects of accented speech on processing affective
      laden information. It shows that higher order semantic processes that involve
      emotion-related aspects are sensitive to a speaker's accent. 

PMID- 25870578
TI  - Commentary on: "Number-space mapping in the newborn chick resembles humans'
      mental number line".

PMID- 25870579
TI  - The state of the art in student engagement.

PMID- 25870580
TI  - Psychoanalytic core competence.

PMID- 25870581
TI  - Unraveling the nature of autism: finding order amid change.
AB  - In this article, we hypothesize that individuals with autism spectrum disorder
      (ASD) are born with a deficit in invariance detection, which is a learning
      process whereby people and animals come to attend the relatively stable patterns
      or structural regularities in the changing stimulus array. This paper synthesizes
      a substantial body of research which suggests that a deficit in the domain
      general perceptual learning process of invariant detection in ASD can lead to a
      cascade of consequences in different developmental domains. We will outline how
      this deficit in invariant detection can cause uncertainty, unpredictability, and
      a lack of control for individuals with ASD and how varying degrees of impairments
      in this learning process can account for the heterogeneity of the ASD phenotype.
      We also describe how differences in neural plasticity in ASD underlie the
      impairments in perceptual learning. The present account offers an alternative to
      prior theories and contributes to the challenge of understanding the
      developmental trajectories that result in the variety of autistic behaviors. 

PMID- 25870583
TI  - Multivariate analysis of traumatic brain injury: development of an assessment
      score.
AB  - Important challenges for the diagnosis and monitoring of mild traumatic brain
      injury (mTBI) include the development of plasma biomarkers for assessing
      neurologic injury, monitoring pathogenesis, and predicting vulnerability for the
      development of untoward neurologic outcomes. While several biomarker proteins
      have shown promise in this regard, used individually, these candidates lack
      adequate sensitivity and/or specificity for making a definitive diagnosis or
      identifying those at risk of subsequent pathology. The objective for this study
      was to evaluate a panel of six recognized and novel biomarker candidates for the
      assessment of TBI in adult patients. The biomarkers studied were selected on the
      basis of their relative brain-specificities and potentials to reflect distinct
      features of TBI mechanisms including (1) neuronal damage assessed by neuron
      specific enolase (NSE) and brain derived neurotrophic factor (BDNF); (2)
      oxidative stress assessed by peroxiredoxin 6 (PRDX6); (3) glial damage and
      gliosis assessed by glial fibrillary acidic protein and S100 calcium binding
      protein beta (S100b); (4) immune activation assessed by monocyte chemoattractant
      protein 1/chemokine (C-C motif) ligand 2 (MCP1/CCL2); and (5) disruption of the
      intercellular adhesion apparatus assessed by intercellular adhesion protein-5
      (ICAM-5). The combined fold-changes in plasma levels of PRDX6, S100b, MCP1, NSE,
      and BDNF resulted in the formulation of a TBI assessment score that identified
      mTBI with a receiver operating characteristic (ROC) area under the curve of 0.97,
      when compared to healthy controls. This research demonstrates that a profile of
      biomarker responses can be used to formulate a diagnostic score that is sensitive
      for the detection of mTBI. Ideally, this multivariate assessment strategy will be
      refined with additional biomarkers that can effectively assess the spectrum of
      TBI and identify those at particular risk for developing neuropathologies as
      consequence of a mTBI event. 

PMID- 25870584
TI  - Efficacy, dosage, and duration of action of branched chain amino Acid therapy for
      traumatic brain injury.
AB  - Traumatic brain injury (TBI) results in long-lasting cognitive impairments for
      which there is currently no accepted treatment. A well-established mouse model of
      mild to moderate TBI, lateral fluid percussion injury (FPI), shows changes in
      network excitability in the hippocampus including a decrease in net synaptic
      efficacy in area CA1 and an increase in net synaptic efficacy in dentate gyrus.
      Previous studies identified a novel therapy consisting of branched chain amino
      acids (BCAAs), which restored normal mouse hippocampal responses and ameliorated
      cognitive impairment following FPI. However, the optimal BCAA dose and length of
      treatment needed to improve cognitive recovery is unknown. In the current study,
      mice underwent FPI then consumed 100 mM BCAA supplemented water ad libitum for 2,
      3, 4, 5, and 10 days. BCAA therapy ameliorated cognitive impairment at 5 and 10
      days duration. Neither BCAA supplementation at 50 mM nor BCAAs when dosed 5 days
      on then 5 days off was sufficient to ameliorate cognitive impairment. These
      results suggest that brain injury causes alterations in hippocampal function,
      which underlie and contribute to hippocampal cognitive impairment, which are
      reversible with at least 5 days of BCAA treatment, and that sustaining this
      effect is dependent on continuous treatment. Our findings have profound
      implications for the clinical investigation of TBI therapy. 

PMID- 25870582
TI  - Tinnitus-related changes in the inferior colliculus.
AB  - Tinnitus is highly complex, diverse, and difficult to treat, in part due to the
      fact that the underlying causes and mechanisms remain elusive. Tinnitus is
      generated within the auditory brain; however, consolidating our understanding of
      tinnitus pathophysiology is difficult due to the diversity of reported effects
      and the variety of implicated brain nuclei. Here, we focus on the inferior
      colliculus (IC), a midbrain structure that integrates the vast majority of
      ascending auditory information and projects via the thalamus to the auditory
      cortex. The IC is also a point of convergence for corticofugal input and input
      originating outside the auditory pathway. We review the evidence, from both
      studies with human subjects and from animal models, for the contribution the IC
      makes to tinnitus. Changes in the IC, caused by either noise exposure or drug
      administration, involve fundamental, heterogeneous alterations in the balance of
      excitation and inhibition. However, differences between hearing loss-induced
      pathology and tinnitus-related pathology are not well understood. Moreover,
      variability in tinnitus induction methodology has a significant impact on
      subsequent neural and behavioral changes, which could explain some of the
      seemingly contradictory data. Nonetheless, the IC is likely involved in the
      generation and persistence of tinnitus perception. 

PMID- 25870585
TI  - Marrow fat and bone: review of clinical findings.
AB  - With growing interest in the connection between fat and bone, there has been
      increased investigation of the relationship with marrow fat in particular.
      Clinical research has been facilitated by the development of non-invasive methods
      to measure bone marrow fat content and composition. Studies in different
      populations using different measurement techniques have established that higher
      marrow fat is associated with lower bone density and prevalent vertebral
      fracture. The degree of unsaturation in marrow fat may also affect bone health.
      Although other fat depots tend to be strongly correlated, marrow fat has a
      distinct pattern, suggesting separate mechanisms of control. Longitudinal studies
      are limited, but are crucial to understand the direct and indirect roles of
      marrow fat as an influence on skeletal health. With greater appreciation of the
      links between bone and energy metabolism, there has been growing interest in
      understanding the relationship between marrow fat and bone. It is well
      established that levels of marrow fat are higher in older adults with
      osteoporosis, defined by either low bone density or vertebral fracture. However,
      the reasons for and implications of this association are not clear. This review
      focuses on clinical studies of marrow fat and its relationship to bone. 

PMID- 25870587
TI  - Brain circuits mediating the orexigenic action of peripheral ghrelin: narrow
      gates for a vast kingdom.

PMID- 25870588
TI  - The new frontiers - creating a "thyroid home".

PMID- 25870586
TI  - The potential use of DNA methylation biomarkers to identify risk and progression
      of type 2 diabetes.
AB  - Type 2 diabetes mellitus (T2D) is a slowly progressive disease that can be
      postponed or even avoided through lifestyle changes. Recent data demonstrate
      highly significant correlations between DNA methylation and the most important
      risk factors of T2D, including age and body mass index, in blood and human
      tissues relevant to insulin resistance and T2D. Also, T2D patients and
      individuals with increased risk of the disease display differential DNA
      methylation profiles and plasticity compared to controls. Accordingly, the novel
      clues to DNA methylation fingerprints in blood and tissues with deteriorated
      metabolic capacity indicate that blood-borne epigenetic biomarkers of T2D
      progression might become a reality. This Review will address the most recent
      associations between DNA methylation and diabetes-related traits in human tissues
      and blood. The overall focus is on the potential of future epigenome-wide
      studies, carried out across tissues and populations with correlations to pre
      diabetes and T2D risk factors, to build up a library of epigenetic markers of
      risk and early progression of T2D. These markers may, tentatively in combination
      with other predictors of T2D development, increase the possibility of individual
      based lifestyle prevention of T2D and associated metabolic diseases. 

PMID- 25870589
TI  - Nutrient requirements and growth physiology of the photoheterotrophic
      Acidobacterium, Chloracidobacterium thermophilum.
AB  - A novel thermophilic, microaerophilic, anoxygenic, and chlorophototrophic member
      of the phylum Acidobacteria, Chloracidobacterium thermophilum strain B(T), was
      isolated from a cyanobacterial enrichment culture derived from microbial mats
      associated with Octopus Spring, Yellowstone National Park, Wyoming. C.
      thermophilum is strictly dependent on light and oxygen and grows optimally as a
      photoheterotroph at irradiance values between 20 and 50 MUmol photons m(-2) s(
      1). C. thermophilum is unable to synthesize branched-chain amino acids (AAs), l
      lysine, and vitamin B12, which are required for growth. Although the organism
      lacks genes for autotrophic carbon fixation, bicarbonate is also required.
      Mixtures of other AAs and 2-oxoglutarate stimulate growth. As suggested from
      genomic sequence data, C. thermophilum requires a reduced sulfur source such as
      thioglycolate, cysteine, methionine, or thiosulfate. The organism can be grown in
      a defined medium at 51(?)C (Topt; range 44-58(?)C) in the pH range 5.5-9.5 (pHopt
      = ~7.0). Using the defined growth medium and optimal conditions, it was possible
      to isolate new C. thermophilum strains directly from samples of hot spring mats
      in Yellowstone National Park, Wyoming. The new isolates differ from the type
      strain with respect to pigment composition, morphology in liquid culture, and
      temperature adaptation. 

PMID- 25870590
TI  - A ten-year search for synchronous cells: obstacles, solutions, and practical
      applications.
AB  - My effort to use synchronously dividing cultures to examine the Escherichia coli
      cell cycle involved a 10-year struggle with failure after failure punctuated by a
      few gratifying successes, especially at the end. In this essay, I recount my
      personal journey in this obsessive experimental pursuit. That narrative is
      followed by a description of a simplified version of the "baby machine," a
      technique that was developed to obtain minimally disturbed, synchronously growing
      E. coli cells. Subsequent studies with this methodology led to an understanding
      of the basic properties of the relationship between chromosome replication and
      cell division. Accordingly, I end this reminiscence with a simple, fool-proof
      graphical strategy for deducing the pattern of chromosome replication during the
      division cycle of cells growing at any rate. 

PMID- 25870591
TI  - High prevalence and risk factors of fecal carriage of CTX-M type extended
      spectrum beta-lactamase-producing Enterobacteriaceae from healthy rural residents
      of Taian, China.
AB  - The study was carried out to understand the prevalence of CTX-M type extended
      spectrum beta-lactamase (ESBL)-harboring Enterobacteriaceae and to analyze risk
      factors related with fecal carriage in healthy rural residents in Taian, China. A
      total of 620 stool samples were collected from rural residents. The ESBL-positive
      Enterobacteriaceae was screened using ChromID ESBL agar, and then further
      confirmed by double-disk diffusion. The CTX-M genes were determined using
      polymerase chain reaction. The risk factors associated with fecal carriage of CTX
      M-positive isolates were analyzed using the standard statistic methods. 458
      isolates carrying CTX-M gene (458/620, 73.9%) were obtained from different
      individuals, and the most dominant genotype was CTX-M-9 group (303/458, 66.2%).
      The dominant species were Escherichia coli (E. coli; 403/458, 88.0%) and
      Klebsiella pneumoniae (K. pneumoniae; 26/458, 5.7%) among the isolates carrying
      CTX-M genes. All the CTX-M producers were resistant to ampicillin, cefazolin,
      cefuroxime, and ceftriaxone, but were all susceptible to biapenem, imipenem, and
      meropenem. The results of multivariate logistic regression model identified the
      enrollment in formal education (OR 2.321; 95% CI 1.302-3.768; P= 0.039), the
      hospitalization history within the last 6 months (OR 1.753; 95% CI 1.127-2.584;
      P= 0.031) and the antibiotics use within the last 6 months (OR 1.892; 95% CI
      1.242-2.903; P= 0.034). The three variables were significantly associated with
      carriage of CTX-M ESBL producers (x (2) = 21.21; df = 3; P< 0.001). The
      prevalence of fecal carriage of CTX-M ESBL-producing Enterobacteriaceae among
      healthy rural humans in Taian was high, and the recent antibiotic use and
      hospitalization history may be the important contributors. 

PMID- 25870592
TI  - Profiling bacterial diversity in a limestone cave of the western Loess Plateau of
      China.
AB  - Bacteria and archaea sustain subsurface cave ecosystems by dominating primary
      production and fueling biogeochemical cyclings, despite the permanent darkness
      and shortage of nutrients. However, the heterogeneity and underlying mechanism of
      microbial diversity in caves, in particular those well connect to surface
      environment are largely unexplored. In this study, we examined the bacterial
      abundance and composition in Jinjia Cave, a small and shallow limestone cave
      located on the western Loess Plateau of China, by enumerating and pyrosequencing
      small subunit rRNA genes. The results clearly reveal the contrasting bacterial
      community compositions in relation to cave habitat types, i.e., rock wall
      deposit, aquatic sediment, and sinkhole soil, which are differentially connected
      to the surface environment. The deposits on the cave walls were dominated by
      putative cave-specific bacterial lineages within the gamma-Proteobacteria or
      Actinobacteria that are routinely found on cave rocks around the world. In
      addition, sequence identity with known functional groups suggests enrichments of
      chemolithotrophic bacteria potentially involved in autotrophic C fixation and
      inorganic N transformation on rock surfaces. By contrast, bacterial communities
      in aquatic sediments were more closely related to those in the overlying soils.
      This is consistent with the similarity in elemental composition between the cave
      sediment and the overlying soil, implicating the influence of mineral chemistry
      on cave microhabitat and bacterial composition. These findings provide compelling
      molecular evidence of the bacterial community heterogeneity in an East Asian
      cave, which might be controlled by both subsurface and surface environments. 

PMID- 25870593
TI  - Fluorescence microscopy visualization of halomucin, a secreted 927 kDa protein
      surrounding Haloquadratum walsbyi cells.
AB  - At the time of its first publication, halomucin from Haloquadratum walsbyi strain
      HBSQ001 was the largest archaeal protein known (9159 aa). It has a predicted
      signal sequence, making it likely to be an extracellular or secreted protein.
      Best BLAST matches were found to be mammalian mucins that protect tissues to
      dehydration and chemical stress. It was hypothesized that halomucin participates
      in protection against desiccation by retaining water in a hull around the
      halophilic organisms that live at the limits of water activity. We visualized
      Haloquadratum cells by staining their intracellular polyhydroxybutyrate granules
      using Nile Blue. Halomucin was stained by immunofluorescence with antibodies
      generated against synthetic peptides derived from the halomucin amino acid
      sequence. Polyhydroxybutyrate stained cells were reconstructed in 3D which
      highlights not only the highly regular square shape but also the extreme flatness
      of Haloquadratum. Double-staining proves halomucin to be extracellular but to be
      only loosely associated to cells in agreement with its hypothesized function. 

PMID- 25870594
TI  - Structure, mineralogy, and microbial diversity of geothermal spring microbialites
      associated with a deep oil drilling in Romania.
AB  - Modern mineral deposits play an important role in evolutionary studies by
      providing clues to the formation of ancient lithified microbial communities. Here
      we report the presence of microbialite-forming microbial mats in different
      microenvironments at 32 degrees C, 49 degrees C, and 65 degrees C around the
      geothermal spring from an abandoned oil drill in Ciocaia, Romania. The mineralogy
      and the macro- and microstructure of the microbialites were investigated,
      together with their microbial diversity based on a 16S rRNA gene amplicon
      sequencing approach. The calcium carbonate is deposited mainly in the form of
      calcite. At 32 degrees C and 49 degrees C, the microbialites show a laminated
      structure with visible microbial mat-carbonate crystal interactions. At 65
      degrees C, the mineral deposit is clotted, without obvious organic residues.
      Partial 16S rRNA gene amplicon sequencing showed that the relative abundance of
      the phylum Archaea was low at 32 degrees C (<0.5%) but increased significantly at
      65 degrees C (36%). The bacterial diversity was either similar to other
      microbialites described in literature (the 32 degrees C sample) or displayed a
      specific combination of phyla and classes (the 49 degrees C and 65 degrees C
      samples). Bacterial taxa were distributed among 39 phyla, out of which 14 had
      inferred abundances >1%. The dominant bacterial groups at 32 degrees C were
      Cyanobacteria, Gammaproteobacteria, Firmicutes, Bacteroidetes, Chloroflexi,
      Thermi, Actinobacteria, Planctomycetes, and Defferibacteres. At 49 degrees C,
      there was a striking dominance of the Gammaproteobacteria, followed by
      Firmicutes, Bacteroidetes, and Armantimonadetes. The 65 degrees C sample was
      dominated by Betaproteobacteria, Firmicutes, [OP1], Defferibacteres, Thermi,
      Thermotogae, [EM3], and Nitrospirae. Several groups from Proteobacteria and
      Firmicutes, together with Halobacteria and Melainabacteria were described for the
      first time in calcium carbonate deposits. Overall, the spring from Ciocaia
      emerges as a valuable site to probe microbes-minerals interrelationships along
      thermal and geochemical gradients. 

PMID- 25870595
TI  - HLA-G Orchestrates the Early Interaction of Human Trophoblasts with the Maternal
      Niche.
AB  - Extravillous trophoblasts (EVTs) play a central role in educating maternal
      leukocytes, endometrial stromal and endothelial cells to generate a receptive
      decidual microenvironment tailored to accept the semi-allogeneic fetus. HLA-G, a
      non-classical HLA class I molecule endowed with immune-regulatory functions, is
      primarily expressed on EVTs lining the placenta and on the naturally occurring
      tolerogenic dendritic cells, named DC-10, which are enriched in the human first
      trimester decidua. Decidual DC-10 are involved in HLA-G-mediated tolerance at the
      maternal-fetal interface. EVTs not only establish a tolerogenic microenvironment
      through the interaction with maternal innate and adaptive cells but also
      orchestrate placenta vascular and tissue remodeling, leading to a successful
      pregnancy. Here, we discuss the potential implications of the HLA-G-mediated
      cross-talk among the cells present at the maternal-fetal interface, and its role
      in maintaining a positive relationship between the mother and the fetus. 

PMID- 25870596
TI  - Modulation of CD44 Activity by A6-Peptide.
AB  - Hyaluronan (HA) is a non-sulfated glycosaminoglycan distributed throughout the
      extracellular matrix that plays a major role in cell adhesion, migration, and
      proliferation. CD44, a multifunctional cell surface glycoprotein, is a receptor
      for HA. In addition, CD44 is known to interact with other receptors and ligands,
      and to mediate a number of cellular functions as well as disease progression.
      Studies have shown that binding of HA to CD44 in cancer cells activates survival
      pathways resulting in cancer cell survival. This effect can be blocked by anti
      CD44 monoclonal antibodies. A6 is a capped, eight l-amino acid peptide (Ac
      KPSSPPEE-NH2) derived from the biologically active connecting peptide domain of
      the serine protease, human urokinase plasminogen activator (uPA). A6 neither
      binds to the uPA receptor (uPAR) nor interferes with uPA/uPAR binding. A6 binds
      to CD44 resulting in the inhibition of migration, invasion, and metastasis of
      tumor cells, and the modulation of CD44-mediated cell signaling. A6 has been
      shown to have no dose-limiting toxicity in animal studies. A6 has demonstrated
      efficacy and an excellent safety profile in Phase 1a, 1b, and 2 clinical trials.
      In animal models, A6 has also exhibited promising results for the treatment of
      diabetic retinopathy and wet age-related macular degeneration through the
      reduction of retinal vascular permeability and inhibition of choroidal
      neovascularization, respectively. Recently, A6 has been shown to be directly
      cytotoxic for B-lymphocytes obtained from patients with chronic lymphocytic
      leukemia expressing the kinase, ZAP-70. This review will discuss the activity of
      A6, A6 modulation of HA and CD44, and a novel strategy for therapeutic
      intervention in disease. 

PMID- 25870597
TI  - Animal models for assessment of infection and inflammation: contributions to
      elucidating the pathophysiology of sudden infant death syndrome.
AB  - Sudden infant death syndrome (SIDS) is still not well understood. It is defined
      as the sudden and unexpected death of an infant without a definitive cause. There
      are numerous hypotheses about the etiology of SIDS but the exact cause or causes
      have never been pinpointed. Examination of theoretical pathologies might only be
      possible in animal models. Development of these models requires consideration of
      the environmental and/or developmental risk factors often associated with SIDS,
      as they need to explain how the risk factors could contribute to the cause of
      death. These models were initially developed in common laboratory animals to test
      various hypotheses to explain these infant deaths - guinea pig, piglet, mouse,
      neonatal rabbit, and neonatal rat. Currently, there are growing numbers of
      researchers using genetically altered animals to examine specific areas of
      interest. This review describes the different systems and models developed to
      examine the diverse hypotheses for the cause of SIDS and their potential for
      defining a causal mechanism or mechanisms. 

PMID- 25870598
TI  - Regulated Expression of miR-155 is Required for iNKT Cell Development.
AB  - Invariant natural killer T cells (iNKT cells) are CD1d-restricted, lipid antigen
      reactive T lymphocytes with immunoregulatory functions. iNKT cell development in
      the thymus proceeds through subsequent stages, defined by the expression of CD44
      and NK1.1, and is dictated by a unique gene expression program, including
      microRNAs. Here, we investigated whether miR-155, a microRNA involved in
      differentiation of most hematopoietic cells, played any role in iNKT cell
      development. To this end, we assessed the expression of miR-155 along iNKT cell
      maturation in the thymus, and studied the effects of miR-155 on iNKT cell
      development using Lck-miR-155 transgenic mice, which over express miR-155 in T
      cell lineage under the lymphocyte-specific protein tyrosine kinase (Lck)
      promoter. We show that miR-155 is expressed by newly selected immature wild-type
      iNKT cells and turned off along iNKT cells differentiation. In transgenic mice,
      miR-155 over-expression resulted in a substantial block of iNKT cell maturation
      at Stage 2, in the thymus toward an overall reduction of peripheral iNKT cells,
      unlike mainstream T cells. Furthermore, the effects of miR-155 over-expression on
      iNKT cell differentiation were cell autonomous. Finally, we identified Ets1 and
      ITK transcripts as relevant targets of miR-155 in iNKT cell differentiation.
      Altogether, these results demonstrate that a tight control of miR-155 expression
      is required for the development of iNKT cells. 

PMID- 25870599
TI  - GRB2 Nucleates T Cell Receptor-Mediated LAT Clusters That Control PLC-gamma1
      Activation and Cytokine Production.
AB  - GRB2 is a ubiquitously expressed adaptor protein required for signaling
      downstream of multiple receptors. To address the role of GRB2 in receptor
      mediated signaling, the expression of GRB2 was suppressed in human CD4+ T cells
      and its role downstream of the T cell receptor (TCR) was examined. Interestingly,
      GRB2 deficient T cells had enhanced signaling from complexes containing the TCR.
      However, GRB2 deficient T cells had substantially reduced production of IL-2 and
      IFN-gamma. This defect was attributed to diminished formation of linker for
      activation of T cells (LAT) signaling clusters, which resulted in reduced MAP
      kinase activation, calcium flux, and PLC-gamma1 recruitment to LAT signaling
      clusters. Add back of wild-type GRB2, but not a novel N-terminal SH3 domain
      mutant, rescued LAT microcluster formation, calcium mobilization, and cytokine
      release, providing the first direct evidence that GRB2, and its ability to bind
      to SH3 domain ligands, is required for establishing LAT microclusters. Our data
      demonstrate that the ability of GRB2 to facilitate protein clusters is equally
      important in regulating TCR-mediated functions as its capacity to recruit
      effector proteins. This highlights that GRB2 regulates signaling downstream of
      adaptors and receptors by both recruiting effector proteins and regulating the
      formation of signaling complexes. 

PMID- 25870600
TI  - Inoculation site from a cutaneous melanoma patient treated with an allogeneic
      therapeutic vaccine: a case report.
AB  - We have developed a therapeutic vaccine consisting of a mixture of lethally
      irradiated allogeneic cutaneous melanoma cell lines with BCG and GM-CSF as
      adjuvants. The CSF-470 vaccine is currently being assayed in a Phase II-III trial
      against medium-dose IFN-alpha2b. All vaccinated patients immunized intradermally
      developed large edematous erythema reactions, which then transformed into
      subcutaneous nodules active for several months. However, vaccine injection sites
      were not routinely biopsied. We describe the case of a female patient, previously
      classified as stage III, but who, due to the simultaneous discovery of bone
      metastases only received one vaccination was withdrawn from the study, and
      continued her treatment elsewhere. This patient developed a post-vaccination
      nodule which was surgically removed 7 weeks later, and allowed to analyze the
      reactivity and immune profiling of the inoculation site. An inflammatory reaction
      with zones of fibrosis, high irrigation, and brisk lymphoid infiltration,
      primarily composed of CD8(+) and CD20(+) lymphocytes, was observed. There were no
      remaining BCG bacilli, and scarce CD4(+) and Foxp3(+) T cells were determined.
      MART-1 Ag was found throughout the vaccination site. CD11c(+) Ag presenting cells
      were either dispersed or forming dense nests. Some CD11c(+) cells proliferated;
      most of them contained intracellular MART-1 Ag, and some interacted with CD8(+)
      lymphocytes. These observations suggest a potent, long-lasting local inflammatory
      response with recruitment of Ag-presenting cells that incorporate melanoma Ags,
      probably leading to Ag presentation to naive T cells. 

PMID- 25870601
TI  - Genome-wide identification, isolation and expression analysis of auxin response
      factor (ARF) gene family in sweet orange (Citrus sinensis).
AB  - Auxin response factors (ARFs) are an important family of proteins in auxin
      mediated response, with key roles in various physiological and biochemical
      processes. To date, a genome-wide overview of the ARF gene family in citrus was
      not available. A systematic analysis of this gene family in citrus was begun by
      carrying out a genome-wide search for the homologs of ARFs. A total of 19
      nonredundant ARF genes (CiARF) were found and validated from the sweet orange. A
      comprehensive overview of the CiARFs was undertaken, including the gene
      structures, phylogenetic analysis, chromosome locations, conserved motifs of
      proteins, and cis-elements in promoters of CiARF. Furthermore, expression
      profiling using real-time PCR revealed many CiARF genes, albeit with different
      patterns depending on types of tissues and/or developmental stages. Comprehensive
      expression analysis of these genes was also performed under two hormone
      treatments using real-time PCR. Indole-3-acetic acid (IAA) and N-1
      napthylphthalamic acid (NPA) treatment experiments revealed differential up
      regulation and down-regulation, respectively, of the 19 citrus ARF genes in the
      callus of sweet orange. Our comprehensive analysis of ARF genes further
      elucidates the roles of CiARF family members during citrus growth and development
      process. 

PMID- 25870602
TI  - Development of salinity tolerance in rice by constitutive-overexpression of genes
      involved in the regulation of programmed cell death.
AB  - Environmental factors contribute to over 70% of crop yield losses worldwide. Of
      these drought and salinity are the most significant causes of crop yield
      reduction. Rice is an important staple crop that feeds more than half of the
      world's population. However among the agronomically important cereals rice is the
      most sensitive to salinity. In the present study we show that exogenous
      expression of anti-apoptotic genes from diverse origins, AtBAG4 (Arabidopsis),
      Hsp70 (Citrus tristeza virus) and p35 (Baculovirus), significantly improves
      salinity tolerance in rice at the whole plant level. Physiological, biochemical
      and agronomical analyses of transgenic rice expressing each of the anti-apoptotic
      genes subjected to salinity treatment demonstrated traits associated with
      tolerant varieties including, improved photosynthesis, membrane integrity, ion
      and ROS maintenance systems, growth rate, and yield components. Moreover, FTIR
      analysis showed that the chemical composition of salinity-treated transgenic
      plants is reminiscent of non-treated, unstressed controls. In contrast, wild type
      and vector control plants displayed hallmark features of stress, including pectin
      degradation upon subjection to salinity treatment. Interestingly, despite their
      diverse origins, transgenic plants expressing the anti-apoptotic genes assessed
      in this study displayed similar physiological and biochemical characteristics
      during salinity treatment thus providing further evidence that cell death
      pathways are conserved across broad evolutionary kingdoms. Our results reveal
      that anti-apoptotic genes facilitate maintenance of metabolic activity at the
      whole plant level to create favorable conditions for cellular survival. It is
      these conditions that are crucial and conducive to the plants ability to
      tolerate/adapt to extreme environments. 

PMID- 25870603
TI  - Partitioning of multivariate phenotypes using regression trees reveals complex
      patterns of adaptation to climate across the range of black cottonwood (Populus
      trichocarpa).
AB  - Local adaptation to climate in temperate forest trees involves the integration of
      multiple physiological, morphological, and phenological traits. Latitudinal
      clines are frequently observed for these traits, but environmental constraints
      also track longitude and altitude. We combined extensive phenotyping of 12
      candidate adaptive traits, multivariate regression trees, quantitative genetics,
      and a genome-wide panel of SNP markers to better understand the interplay among
      geography, climate, and adaptation to abiotic factors in Populus trichocarpa.
      Heritabilities were low to moderate (0.13-0.32) and population differentiation
      for many traits exceeded the 99th percentile of the genome-wide distribution of
      FST, suggesting local adaptation. When climate variables were taken as predictors
      and the 12 traits as response variables in a multivariate regression tree
      analysis, evapotranspiration (Eref) explained the most variation, with subsequent
      splits related to mean temperature of the warmest month, frost-free period (FFP),
      and mean annual precipitation (MAP). These grouping matched relatively well the
      splits using geographic variables as predictors: the northernmost groups (short
      FFP and low Eref) had the lowest growth, and lowest cold injury index; the
      southern British Columbia group (low Eref and intermediate temperatures) had
      average growth and cold injury index; the group from the coast of California and
      Oregon (high Eref and FFP) had the highest growth performance and the highest
      cold injury index; and the southernmost, high-altitude group (with high Eref and
      low FFP) performed poorly, had high cold injury index, and lower water use
      efficiency. Taken together, these results suggest variation in both temperature
      and water availability across the range shape multivariate adaptive traits in
      poplar. 

PMID- 25870604
TI  - Oil palm natural diversity and the potential for yield improvement.
AB  - African oil palm has the highest productivity amongst cultivated oleaginous
      crops. Species can constitute a single crop capable to fulfill the growing global
      demand for vegetable oils, which is estimated to reach 240 million tons by 2050.
      Two types of vegetable oil are extracted from the palm fruit on commercial scale.
      The crude palm oil and kernel palm oil have different fatty acid profiles, which
      increases versatility of the crop in industrial applications. Plantations of the
      current varieties have economic life-span around 25-30 years and produce fruits
      around the year. Thus, predictable annual palm oil supply enables marketing plans
      and adjustments in line with the economic forecasts. Oil palm cultivation is one
      of the most profitable land uses in the humid tropics. Oil palm fruits are the
      richest plant source of pro-vitamin A and vitamin E. Hence, crop both alleviates
      poverty, and could provide a simple practical solution to eliminate global pro
      vitamin A deficiency. Oil palm is a perennial, evergreen tree adapted to
      cultivation in biodiversity rich equatorial land areas. The growing demand for
      the palm oil threatens the future of the rain forests and has a large negative
      impact on biodiversity. Plant science faces three major challenges to make oil
      palm the key element of building the future sustainable world. The global average
      yield of 3.5 tons of oil per hectare (t) should be raised to the full yield
      potential estimated at 11-18t. The tree architecture must be changed to lower
      labor intensity and improve mechanization of the harvest. Oil composition should
      be tailored to the evolving needs of the food, oleochemical and fuel industries.
      The release of the oil palm reference genome sequence in 2013 was the key step
      toward this goal. The molecular bases of agronomically important traits can be
      and are beginning to be understood at the single base pair resolution, enabling
      gene-centered breeding and engineering of this remarkable crop. 

PMID- 25870605
TI  - Simple preparation of plant epidermal tissue for laser microdissection and
      downstream quantitative proteome and carbohydrate analysis.
AB  - The outwardly directed cell wall and associated plasma membrane of epidermal
      cells represent the first layers of plant defense against intruding pathogens.
      Cell wall modifications and the formation of defense structures at sites of
      attempted pathogen penetration are decisive for plant defense. A precise
      isolation of these stress-induced structures would allow a specific analysis of
      regulatory mechanism and cell wall adaption. However, methods for large-scale
      epidermal tissue preparation from the model plant Arabidopsis thaliana, which
      would allow proteome and cell wall analysis of complete, laser-microdissected
      epidermal defense structures, have not been provided. We developed the adhesive
      tape - liquid cover glass technique (ACT) for simple leaf epidermis preparation
      from A. thaliana, which is also applicable on grass leaves. This method is
      compatible with subsequent staining techniques to visualize stress-related cell
      wall structures, which were precisely isolated from the epidermal tissue layer by
      laser microdissection (LM) coupled to laser pressure catapulting. We successfully
      demonstrated that these specific epidermal tissue samples could be used for
      quantitative downstream proteome and cell wall analysis. The development of the
      ACT for simple leaf epidermis preparation and the compatibility to LM and
      downstream quantitative analysis opens new possibilities in the precise
      examination of stress- and pathogen-related cell wall structures in epidermal
      cells. Because the developed tissue processing is also applicable on A. thaliana,
      well-established, model pathosystems that include the interaction with powdery
      mildews can be studied to determine principal regulatory mechanisms in plant
      microbe interaction with their potential outreach into crop breeding. 

PMID- 25870606
TI  - Diversity and function of maize pollen coat proteins: from biochemistry to
      proteomics.
AB  - Maize (Zea mays L.) is globally cultivated as one of the most important grain
      crops. As a wind-pollinated species, maize produces a large quantity of pollen
      grains that heavier and larger compared to Arabidopsis. Maize is an important
      model plant in pollen biology of monocots. The pollen coat, the outermost layer
      of pollen, plays a vital role in pollen-stigma interactions and successful
      fertilization. Pollen coat proteins (PCPs), which confer species specificity, are
      required for pollen adhesion, recognition, hydration, and germination on the
      stigma. Thus, PCPs have attracted intensive research efforts in plant science for
      decades. However, only a few PCPs in maize have been characterized to date,
      whereas the functions of most maize PCPs remain unclear. In this review, we
      summarize the current knowledge of maize PCPs with regard to protein
      constituents, synthesis and transport, and functions by comparison with the model
      plant Arabidopsis thaliana and Brassica plants. An understanding of the
      comprehensive knowledge of maize PCPs will help to illuminate the mechanism by
      which PCPs are involved in pollen-stigma interactions in maize and other crop
      plants. 

PMID- 25870607
TI  - Towards a common bean proteome atlas: looking at the current state of research
      and the need for a comprehensive proteome.

PMID- 25870608
TI  - A quantitative analysis of stem cell homeostasis in the Arabidopsis columella
      root cap.
AB  - The Lugol's staining method has been widely used to detect changes in the
      maintenance of stem cell fate in the columella root cap of Arabidopsis roots
      since the late 1990s. However, various limitations of this method demand for
      additional or complementary new approaches. For instance, it is unable to reveal
      the division rate of columella root cap stem cells. Here we report that, by
      labeling dividing stem cells with 5-ethynyl-2'-deoxyuridine (EdU), the number and
      distribution of their labeled progeny can be studied so that the division rate of
      stem cells can be measured quantitatively and in addition, that the progression
      of stem cell progeny differentiation can be assessed in combination with Lugol's
      staining. EdU staining takes few hours and visualization of the stain
      characteristics of columella root cap can be performed easily under confocal
      microscopes. This simple technology, when used together with Lugol's staining,
      provides a novel quantitative method to study the dynamics of stem cell behavior
      that govern homeostasis in the Arabidopsis columella root cap. 

PMID- 25870609
TI  - Global impact of KRAS mutation patterns in FOLFOX treated metastatic colorectal
      cancer.
AB  - BACKGROUND: Colorectal cancer (CRC) is one of the most frequent events in
      oncology. Advances in molecular understanding of the processes of carcinogenesis
      have shed light on the fundamental mechanisms of tumorigenesis. Currently,
      knowledge of the molecular basis of its pathogenesis is being used to improve
      patient care and devise more rational therapeutics. Still, the role played by the
      mutation patterns of mutated genes in the clinical outcomes that patients on
      pharmacological treatment receive remains unclear. In this study, we propose to
      analyze the different clinical outcomes and disease prognosis of patients with
      stage IV CRC treated with FOLFOX chemotherapy (fluorouracil, leucovorin,
      oxaliplatin) based on different Kirsten ras (KRAS) mutation patterns. METHODS: In
      this cohort study, 148 patients diagnosed with stage IV CRC and treated with
      FOLFOX were studied between 2008 and 2013. Mutational status of KRAS was
      determined. Progression-free survival (PFS) and overall survival (OS) were
      measured, and all deaths were verified. Survival analysis was performed using
      Kaplan-Meier analysis, comparison among groups was analyzed using the log-rank
      test, and multivariate analysis was conducted using Cox proportional-hazards
      regression. RESULTS: Among a total of 148 patients, 48 (32%) had mutated KRAS,
      77% at codon 12 and 23% at codon 13. The PFS was significantly worse in the
      mutant KRAS patients in comparison to wild type KRAS patients (p < 0.05). The OS
      did not show significant differences between the two groups. Multivariate
      analysis showed KRAS mutation as an independent negative prognostic factor for
      PFS. Among the various subtypes of KRAS mutation, G12D was significantly
      associated with a poor prognosis in PFS (p = 0.02). CONCLUSION: In our
      population, the KRAS mutation had an adverse impact on the prognosis for stage IV
      CRC patients treated with the FOLFOX regimen.

PMID- 25870610
TI  - Relationship between lipoprotein (a) and micro/macro complications in type 2
      diabetes mellitus: a forgotten target.
AB  - OBJECTIVES: Increased lipoprotein (a) serum concentrations seems to be a
      cardiovascular risk factor; this has not been confirmed in extracoronary
      atherosclerosis complications. We therefore wished to gain a deeper insight into
      relationship between the plasma concentrations of lipoprotein (a) and the micro-
      and macro-vascular complications of type 2 diabetes mellitus and to identify
      possible differences in this association. METHODS: This is a descriptive
      observational cross-sectional study. Two-hundred and seventeen elderly patients
      with type 2 diabetes mellitus were included from the internal medicine outclinic.
      Anthropometric data, analytical data (insulin reserve, basal and postprandial
      peptide C, glycosylated hemoglobin, renal parameters, lipid profile and clinical
      data as hypertension, obesity, micro- and macrovascular complications were
      collected. RESULTS: Patients were grouped according to the type 2 diabetes
      mellitus time of evolution. The mean plasma concentration of lipoprotein (a) was
      22.2 +/- 17.3 mg/dL (22.1 +/- 15.9 mg/dL for males, and 22.1 +/- 18.4 mg/dL for
      females). Patients with hypertension, coronary heart disease, cerebrovascular
      accident, microalbuminuria and proteinuria presented a statistically significant
      increased level of lipoprotein (a). Similarly, the patients with hyperlipoprotein
      (a) (>= 30 mg/dL) presented significantly increased levels of urea and total
      cholesterol. In the multivariate regression model, the level of lipoprotein (a)
      is positively correlated with coronary heart disease and diabetic nephropathy (P
      < 0.01 and P < 0.005, respectively). CONCLUSIONS: The elevation of plasma levels
      of lipoprotein (a) are associated with the development of coronary heart disease
      and diabe tic nephropathy. Therefore, we consider that the determination of
      lipoprotein (a) may be a prognostic marker of vascular complications in patients
      with type 2 diabetes mellitus.

PMID- 25870611
TI  - Evaluation of CA125 and NT-proBNP values in patients undergoing transcatheter
      aortic valve implantation.
AB  - BACKGROUND: Transcatheter aortic valve implantation (TAVI) is a minimally
      invasive, emerging therapy in surgically high risk, or inoperable patients.
      Parameters used for risk classification have some deficiencies in the selection
      of patients. The objective of this study is to evaluate the impact of TAVI on
      carbohydrate antigen 125 (CA125) and N-Terminal pro Brain-type Natriuretic
      Peptide (NT-proBNP) as biomarkers that have been used frequently in recent years,
      and also the relationship of these biomarkers to prognosis. METHODS & RESULTS:
      Transcatheter aortic valve implantation was practiced on 31 patients in this
      study. Then, CA125 and NT-proBNP levels studied in patients prior to and after
      the TAVI were evaluated. The patients were also grouped in accordance with their
      left ventricular ejection fraction (LVEF) and CA125 levels (LVEF >= 40% and <
      40%; CA125 <= 35 U/L and > 35 U/L). The TAVI operation was successfully performed
      in all patients. There was no in-hospital mortality and substantial improvement
      in functional capacity was detected at follow ups. In addition, a statistically
      significant decrease was detected in post-TAVI CA125 and NT-proBNP levels of all
      patients (CA125 83.8 +/- 18.1 U/L vs. 64.3 +/- 14.2 U/L, P = 0.008; NT-proBNP:
      4633.6 +/- 627.6 pg/mL vs. 2866.3 +/- 536.8 pg/mL, P < 0.001). In groups divided
      according to the CA125 levels, there was also statistically significant post-TAVI
      decline in CA125 levels. Within CA125 > 35 U/L and LVEF < 40% groups, the
      permanent need for a pacemaker was required in one (3.2%) patient and mortality
      was observed in two (6.4%) patients after TAVI at follow up. CONCLUSIONS: The
      results show that TAVI can be performed effectively and reliably in patients with
      high baseline levels of CA125 and NT-proBNP. These biomarkers are reduced
      substantially with TAVI, while high biomarker levels are associated with
      undesired events, and certainly, these biomarkers can be used for risk
      classifications in patient selection for TAVI.

PMID- 25870612
TI  - Factors influencing the functional significance in intermediate coronary
      stenosis.
AB  - OBJECTIVE: To analyze the influencing factors of the functional significance
      determined by fractional flow reserve (FFR) in intermediate coronary artery
      stenosis. METHODS: The study enrolled 143 patients with 203 intermediate coronary
      lesions. Pressure-derived FFR of these lesions was gained at maximal hyperemia
      induced by intravenous adenosine infusion. An FFR < 0.80 was considered as
      abnormal functional significance. Anatomic parameters at the lesion sites were
      obtained by off-line quantitative coronary angiography analysis (QCA). The
      predictive value of the demographic characteristics and anatomic parameters for
      FFR in these intermediate lesions was assessed using multiple linear and binary
      logistic regression analysis. RESULTS: Overall, FFR < 0.8 was found in 70 (34%)
      of the total 203 intermediate coronary lesions. FFR values were positively
      correlated with QCA-measured minimum lumen diameters (MLD, r = 0.372, P = 0.000)
      and the reference vessel diameters (RVD, r = 0.217, P = 0.002) were negatively
      correlated with percent area stenosis (AS, r = -0.251, P = 0.000) and percent
      diameter stenosis (DS, r = -0.210, P = 0.000). Age, MLD and the lesion location
      in different coronary arteries were the independent determinants of FFR < 0.8.
      CONCLUSIONS: MLD can predict the functional significance of intermediate coronary
      stenosis, while age and the lesion location in different coronary arteries should
      be taken into account as important influencing factors of FFR values.

PMID- 25870613
TI  - A poor performance in comprehensive geriatric assessment is associated with
      increased fall risk in elders with hypertension: a cross-sectional study.
AB  - BACKGROUND: Fall and serious fall injuries have become a major health concern for
      elders. Many factors including blood pressure and anti-hypertensive medication
      application were reported as hazards of fall. The purpose of this study was to
      determine if age related systemic functional decline related with increased fall
      risks in elderly patients with hypertension. METHODS: A total of 342 elderly
      hypertension patients (age 79.5 +/- 6.7 years, male 63.8%) were recruited to the
      study. Comprehensive geriatric assessment (CGA), including measurements about
      activity of daily living (ADL), nutrition, cognition, depression, numbers of
      prescription medication and number of clinical diagnosis, was conducted to
      evaluate the physical and mental status of each participants. Fall risk was
      evaluated by Morse fall scale, Tinetti performance oriented mobility assessment
      (POMA) and history of fall in the recent year. Participants were grouped into
      tertiles according to CGA score. Correlation between CGA and fall risk was
      analyzed through SPSS 18.0. RESULTS: Participants with higher CGA score were
      likely to be older, had a lower body mass index (BMI), and a higher prevalence of
      cardiovascular disease, chronic obstructive pulmonary disease (COPD),
      cerebrovascular disease and osteoarthropathia. Participants in higher tertile of
      CGA score got increased prevalence of fall risk than those in lower tertile (P <
      0.01 T3 vs. T1, P < 0.01 T3 vs. T2). Correlation analysis and regression analysis
      showed significant association between CGA and Morse fall scale (P < 0.001), as
      well as CGA and POMA (P < 0.001). Meanwhile, CGA components also showed co
      relationships with increase fall risks. After adjusting age, BMI, benzodiazepine
      use, cardiovascular disease, cerebrovascular disease, COPD and osteoarthropathia,
      both history of fall in the recent year and rising Morse fall scale were
      significantly associated with ADL impairment (OR: 2.748, 95%CI: 1.598-4.725),
      (OR: 3.310, 95%CI: 1.893-5.788). Decreased Tinetti POMA score was associated with
      Mini-Mental State Examination (MMSE) (OR: 4.035, 95%CI: 2.100-7.751), ADL (OR:
      2.380, 95%CI: 1.357-4.175) and shortened MNA form (MNA-SF) impairment (OR: 2.692,
      95%CI: 1.147-6.319). CONCLUSIONS: In elderly adults with hypertension, impaired
      physical and mental function is associated with increased fall risk. Further
      study is required to investigate possible mediators for the association and
      effective interventions.

PMID- 25870614
TI  - Associations between serum potassium and sodium levels and risk of hypertension:
      a community-based cohort study.
AB  - OBJECTIVE: Several studies have examined the relationships between dietary
      potassium and sodium and hypertension, but few have evaluated the association
      between serum potassium or sodium and risk of incident hypertension. We therefore
      investigated the associations between serum potassium and sodium and risk of
      incident hypertension in a Chinese community-based population. METHODS: A total
      of 839 normotensive individuals without cardiovascular disease from the Chinese
      Multi-Provincial Cohort Study who took part in the baseline examination in 2007
      2008 and the follow-up survey in 2012-2013 were included in this study. Odds
      ratios (OR) and 95% confidence intervals (95%CI) for baseline serum potassium and
      sodium in relation to the risk of new-onset hypertension were evaluated using
      multivariate logistic regression models. RESULTS: During five years of follow-up,
      218 (26.0%) individuals progressed to hypertension. Logistic regression adjusting
      for multiple confounders showed that every 1 mEq/L increment in baseline serum
      potassium level was associated with a 75% increased risk of hypertension (OR:
      1.75; 95%CI: 1.01-3.04; P = 0.04). Compared with adults with serum potassium
      level of 4.20-4.79 mEq/L, adults with level >= 4.80 mEq/L had an 84% increased
      risk of hypertension (OR: 1.84; 95%CI: 1.14-2.96; P = 0.01). There was no
      significant association between serum sodium and risk of hypertension (OR: 0.96;
      95%CI: 0.89-1.04; P = 0.33). CONCLUSIONS: Baseline serum potassium level, but not
      baseline serum sodium level, was positively related to the risk of incident
      hypertension in the Chinese population.

PMID- 25870615
TI  - G-protein beta 3 subunit polymorphisms and essential hypertension: a case-control
      association study in northern Han Chinese.
AB  - OBJECTIVE: To explore the association between the three polymorphisms [ C825T,
      C1429T and G(-350)A] of the gene encoding the G protein beta 3 subunit (GNB3) and
      hypertension by performing a case-control study in the northern Han Chinese
      population. METHODS: We recruited 731 hypertensive patients and 673 control
      subjects (the calculated power value was > 0.8). Genotyping was performed to
      identify C825T, C1429T and G(-350)A polymorphisms using the TaqMan assay.
      Comparisons of allelic and genotypic frequencies between cases and controls were
      made by using the chi-square test. Logistic regression analyses were performed to
      investigate the relationships between the three polymorphisms of GNB3 gene under
      different genetic models (additive, dominant and recessive models). RESULTS: The
      genotype distribution and allele frequencies of C825T, C1429T and G(-350)A
      polymorphisms did not differ significantly between hypertensive patients and
      control subjects, either when the full sample was assessed, or when the sample
      was stratified by gender. No significant association was observed between C825T,
      C1429T and G(-350)A polymorphisms and the risk of essential hypertension in any
      genetic model. Linkage disequilibrium was only detected between C825T and C1429T
      polymorphisms. Haplotype analyses observed that none of the three estimated
      haplotypes significantly increased the risk of hypertension. CONCLUSIONS: Our
      study suggested that the GNB3 gene polymorphisms [C825T, C1429T and G(-350)A]
      were not significantly associated with essential hypertension in northern Han
      Chinese population.

PMID- 25870616
TI  - Combination therapy reduces the incidence of no-reflow after primary per
      cutaneous coronary intervention in patients with ST-segment elevation acute
      myocardial infarction.
AB  - BACKGROUND: No-reflow is associated with an adverse outcome and higher mortality
      in patients with ST-segment elevation acute myocardial infarction (STEMI) who
      undergo percutaneous coronary intervention (PCI) and is considered a dynamic
      process characterized by multiple pathogenetic components. The aim of this study
      was to investigate the effectiveness of a combination therapy for the prevention
      of no-reflow in patient with acute myocardial infarction (AMI) undergoing primary
      PCI. METHODS: A total of 621 patients with STEMI who underwent emergency primary
      PCI were enrolled in this study. Patients with high risk of no-reflow (no-flow
      score >= 10, by using a no-flow risk prediction model, n = 216) were randomly
      divided into a controlled group (n = 108) and a combination therapy group (n =
      108). Patients in the controlled group received conventional treatment, while
      patients in combination therapy group received high-dose (80 mg) atorvastatin pre
      treatment, intracoronary administration of adenosine (140 ug/min per kilogram)
      during PCI procedure, platelet membrane glycoprotein IIb/IIIa receptor antagonist
      (tirofiban, 10ug/kg bolus followed by 0.15 ug/kg per minute) and thrombus
      aspiration. Myocardial contrast echocardiography was performed to assess the
      myocardial perfusion 72 h after PCI. Major adverse cardiac events (MACE) were
      followed up for six months. RESULTS: Incidence of no-reflow in combination
      therapy group was 2.8%, which was similar to that in low risk group 2.7% and was
      significantly lower than that in control group (35.2%, P < 0.01). The myocardial
      perfusion (A * beta) values were higher in combination therapy group than that in
      control group 72 h after PCI. After 6 months, there were six (6.3%) MACE events
      (one death, two non-fatal MIs and three revascularizations) in combination
      therapy group and 12 (13.2%) (four deaths, three non-fatal MIs and five
      revascularizations, P < 0.05) in control group. CONCLUSIONS: Combination of
      thrombus aspiration, high-dose statin pre-treatment, intracoronary administration
      of adenosine during PCI procedure and platelet membrane glycoprotein IIb/IIIa
      receptor antagonist reduce the incidence of no-reflow after primary PCI in
      patients with acute myocardial infarction who are at high risk of no-reflow.

PMID- 25870617
TI  - Inappropriate use of digoxin in patients presenting with digoxin toxicity.
AB  - BACKGROUND: Digoxin remains widely used today despite its narrow therapeutic
      index and toxicity. The objective of this study was to investigate the percentage
      of inappropriate use of digoxin and long-term outcomes of elderly patients
      hospitalized for digoxin toxicity. METHODS: The study included 99 consecutive
      patients hospitalized for digoxin toxicity. The other study criteria for the
      inappropriate use of digoxin was regarded if participants having depressed left
      ventricular systolic function (ejection fraction < 45%) who were not on optimal
      medical therapy including beta-blocker and angiotensin-converting-enzyme
      inhibitor therapy or if participants having permanent AF who were not on optimal
      beta-blocker therapy. RESULTS: Appropriate digoxin usage was confirmed in 33 of
      patients in spite of its narrow therapeutic index. A total of 16 of 99 patients
      died, with a mean follow-up time of 22.1 +/- 10.3 months. CONCLUSIONS: Contrary
      to popular belief, the rate of inappropriate digoxin usage remains high. On
      account of its narrow therapeutic index and toxicity, digoxin should be used more
      carefully according to the current evidence and guidelines.

PMID- 25870618
TI  - Coronary artery bypass grafting in the octogenarians: should we intervene, or
      leave them be?
AB  - OBJECTIVE: Coronary artery bypass grafting (CABG) is gradually increasing in the
      elderly population. We aimed to investigate the risk factors and the results of
      CABG along with the long term survival in patients at an age of 80 and older.
      METHODS: Between January 2002 and December 2011, a total of 101 consecutive
      patients at an age of 80 and older who underwent CABG in our hospital were
      included in the study. The patients were followed and the long-term survival was
      estimated. RESULTS: The mean age of the patients was 82.98 +/- 2.27 years. Sixty
      four (63.4%) were males and 37 (36.6%) were females. Emergency surgery, duration
      of cardiopulmonary bypass, the intensive care unit (ICU) stay, inotropic support,
      intra aortic balloon pulsation application, amount of erythrocyte transfusion and
      fresh frozen plasma transfusion and ventilation period were significantly higher
      in the patients who died in the hospital. The duration of cardiopulmonary bypass
      (CPB) was found to be an independent predictor of mortality (OR: 1.18, 95% CI
      1.01-1.38, P = 0.034). The in-hospital mortality was 16.8%. Kaplan-Meier analyses
      revealed a survival ratio of 91.3% at one year, 82.9% at three years and 69.0% at
      five years. CONCLUSIONS: Patients at the age of 80 and older can be candidates
      for the CABG procedure bearing in mind that they may have a longer ventilation
      period and intensive care unit stay. The morbidity and mortality of this age
      group is considered within an acceptable range. Approaches to minimize CPB, or
      the choice of off-pump surgery, may be a preventive method to lower the incidence
      of mortality. Hence, CABG may be performed in this age group with a satisfactory
      survival ratio.

PMID- 25870619
TI  - Targeting histone deacetylases: perspectives for epigenetic-based therapy in
      cardio-cerebrovascular disease.
AB  - Although the pathogenesis of cardio-cerebrovascular disease (CCVD) is
      multifactorial, an increasing number of experimental and clinical studies have
      highlighted the importance of histone deacetylase (HDAC)-mediated epigenetic
      processes in the development of cardio-cerebrovascular injury. HDACs are a family
      of enzymes to balance the acetylation activities of histone acetyltransferases on
      chromatin remodeling and play essential roles in regulating gene transcription.
      To date, 18 mammalian HDACs are identified and grouped into four classes based on
      similarity to yeast orthologs. The zinc-dependent HDAC family currently consists
      of 11 members divided into three classes (class I, II, and IV) on the basis of
      structure, sequence homology, and domain organization. In comparison, class III
      HDACs (also known as the sirtuins) are composed of a family of NAD(+)-dependent
      protein-modifying enzymes related to the Sir2 gene. HDAC inhibitors are a group
      of compounds that block HDAC activities typically by binding to the zinc
      containing catalytic domain of HDACs and have displayed anti-inflammatory and
      antifibrotic effects in the cardio-cerebrovascular system. In this review, we
      summarize the current knowledge about classifications, functions of HDACs and
      their roles and regulatory mechanisms in the cardio-cerebrovascular system.
      Pharmacological targeting of HDAC-mediated epigenetic processes may open new
      therapeutic avenues for the treatment of CCVD. 

PMID- 25870620
TI  - Drug therapy for heart failure in older patients-what do they want?
AB  - Chronic heart failure (CHF) is predominantly seen in older patients, and
      therefore real life medicine often requires the extrapolation of findings from
      trials conducted in much younger populations. Prescribing patterns and potential
      benefits in the elderly are heavily influenced by polypharmacy and co-morbid
      pathologies. Increasing longevity may become less relevant in the frail elderly,
      whereas improving quality of life (QoL) often becomes priority; the onus being on
      improving wellbeing, maintaining independence for longer, and delaying
      institutionalisation. Specific studies evaluating elderly patients with CHF are
      lacking and little is known regarding the tolerability and side-effect profile of
      evidence based drug therapies in this population. There has been recent interest
      on the impact of heart rate in patients with symptomatic CHF. Ivabradine, with
      selective heart rate lowering capabilities, is of benefit in patients with CHF
      and left ventricular systolic dysfunction in sinus rhythm, resulting in reduction
      of heart failure hospitalisation and cardiovascular death. This manuscript will
      focus on CHF and the older patient and will discuss the impact of heart rate,
      drug therapies and tolerability. It will also highlight the unmet need for
      specific studies that focus on patient-centred study end points rather than
      mortality targets that characterise most therapeutic trials. An on-going study
      evaluating the impact of ivabradine on QoL that presents a unique opportunity to
      evaluate the tolerability and impact of an established therapy on a wide range of
      real life, older patients with CHF will be discussed. 

PMID- 25870622
TI  - A very rare case of late diagnosis of cor triatriatum sinistrum.
AB  - We presented a 73-year-old patient with a history of hospitalizations for heart
      failure as well as treatment for arterial hypertension and permanent atrial
      fibrillation and who was found to have cor triatriatum sinistrum in combination
      with bicuspid aortic valve. Patient refused surgical correction, but his
      condition improved on conservative therapy for heart failure and atrial
      fibrillation. 

PMID- 25870621
TI  - An overview of PCI in the very elderly.
AB  - Cardiovascular disease, and in particular ischemic heart disease (IHD), is a
      major cause of morbidity and mortality in the very elderly (> 80 years)
      worldwide. These patients represent a rapidly growing cohort presenting for
      percutaneous coronary intervention (PCI), now constituting more than one in five
      patients treated with PCI in real-world practice. Furthermore, they often have
      greater ischemic burden than their younger counterparts, suggesting that they
      have greater scope of benefit from coronary revascularization therapy. Despite
      this, the very elderly are frequently under-represented in clinical
      revascularization trials and historically there has been a degree of physician
      reluctance in referring them for PCI procedures, with perceptions of
      disappointing outcomes, low success and high complication rates. Several issues
      have contributed to this, including the tendency for older patients with IHD to
      present late, with atypical symptoms or non-diagnostic ECGs, and reservations
      regarding their procedural risk-to-benefit ratio, due to shorter life expectancy,
      presence of comorbidities and increased bleeding risk from antiplatelet and
      anticoagulation medications. However, advances in PCI technology and techniques
      over the past decade have led to better outcomes and lower risk of complications
      and the existing body of evidence now indicates that the very elderly actually
      derive more relative benefit from PCI than younger populations. Importantly, this
      applies to all PCI settings: elective, urgent and emergency. This review
      discusses the role of PCI in the very elderly presenting with chronic stable IHD,
      non ST-elevation acute coronary syndrome, and ST-elevation myocardial infarction.
      It also addresses the clinical challenges met when considering PCI in this cohort
      and the ongoing need for research and development to further improve outcomes in
      these challenging patients. 

PMID- 25870623
TI  - A new device for paravalvular leak closure.
AB  - Percutaneous closure of a prosthetic paravalvular leak (PVL) is a challenging
      procedure. Operators must use devices constructed for other applications. We
      present the use of a device which is specifically designed for PVL closure. To
      the best of our knowledge, there is no publication in MEDLINE reporting the use
      of the device. 

PMID- 25870624
TI  - Underpad weight to estimate urine output in adult patients with urinary
      incontinence.

PMID- 25870625
TI  - Updates on coagulation management in cardiac surgery.

PMID- 25870626
TI  - Thrombolytic-plus-Anticoagulant Therapy versus Anticoagulant-Alone Therapy in
      Submassive Pulmonary Thromboembolism (TVASPE Study): A Randomized Clinical Trial.
AB  - BACKGROUND: The use of thrombolytic agents in the treatment of hemodynamically
      stable patients with acute submassive pulmonary embolism (PTE) remains
      controversial. We, therefore, conducted this study to compare the effect of
      thrombolytic plus anticoagulation versus anticoagulation alone on early death and
      adverse outcome following submassive PTE. METHODS: We conducted a study of
      patients with acute pulmonary embolism and pulmonary hypertension or right
      ventricular dilatation/dysfunction but without arterial hypotension or shock. The
      patients were randomly assigned in a single-blind fashion to receive an
      anticoagulant [Enoxaparin (1 mg/kg twice a day)] plus a thrombolytic [Alteplase
      (100 mg) or Streptokinase (1500000 u/2 hours)] or an anticoagulant [Enoxaparin (1
      mg/kg twice a day)] alone. The primary endpoint was in-hospital death or clinical
      deterioration requiring an escalation of treatment. The secondary endpoints of
      the study were major bleeding, pulmonary hypertension, right ventricular
      dilatation at the end of the first week, and exertional dyspnea at the end of the
      first month. RESULTS: Of 50 patients enrolled, 25 patients were randomly assigned
      to receive an anticoagulant plus a thrombolytic and the other 25 patients were
      given an anticoagulant alone. The incidence of the primary endpoints was
      significantly higher in the anticoagulant-alone group than in the thrombolytic
      plus-anticoagulant group (p value = 0.022). At the time of discharge, pulmonary
      artery pressure was significantly higher in the anticoagulant-alone group than in
      the thrombolytic-plus-anticoagulant group (p value = 0.018); however, reduction
      in the right ventricular size or normalization of the right ventricle showed non
      significant differences between the two groups. There was no significant
      difference regarding the New York Heat Association (NYHA) functional class
      between the two groups at the end of the first month (p value = 0.213). No fatal
      bleeding or cerebral bleeding occurred in the patients receiving an anticoagulant
      plus a thrombolytic. CONCLUSION: When given in conjunction with anticoagulants,
      thrombolytics may improve the clinical course of stable patients who have acute
      submassive pulmonary embolism and prevent clinical deterioration.

PMID- 25870627
TI  - Mitral regurgitation after percutaneous balloon mitral valvotomy in patients with
      rheumatic mitral stenosis: a single-center study.
AB  - BACKGROUND: Percutaneous balloon mitral valvotomy (BMV) is the gold standard
      treatment for rheumatic mitral stenosis (MS) in that it causes significant
      changes in mitral valve area (MVA) and improves leaflet mobility. Development of
      or increase in mitral regurgitation (MR) is common after BMV. This study
      evaluated MR severity and its changes after BMV in Iranian patients. METHODS: We
      prospectively evaluated consecutive patients with severe rheumatic MS undergoing
      BMV using the Inoue balloon technique between February 2010 and January 2013 in
      Madani Heart Center, Tabriz, Iran. New York Heart Association (NYHA) functional
      class and echocardiographic and catheterization data, including MVA, mitral valve
      mean and peak gradient (MVPG and MVMG), left atrial (LA) pressure, pulmonary
      artery systolic pressure (PAPs), and MR severity before and after BMV, were
      evaluated. RESULTS: Totally, 105 patients (80% female) at a mean age of 45.81 +/-
      13.37 years were enrolled. NYHA class was significantly improved after BMV: 55.2%
      of the patients were in NYHA functional class III before BMV compared to 36.2%
      after the procedure (p value < 0.001). MVA significantly increased (mean area =
      0.64 +/- 0.29 cm(2) before BMV vs. 1.90 +/- 0.22 cm(2) after BMV; p value <
      0.001) and PAPs, LA pressure, MVPG, and MVMG significantly decreased. MR severity
      did not change in 82 (78.1%) patients, but it increased in 18 (17.1%) and
      decreased in 5 (4.8%) patients. Patients with increased MR had a significantly
      higher calcification score (2.03 +/- 0.53 vs.1.50 +/- 0.51; p value < 0.001) and
      lower MVA before BMV (0.81 +/- 0.23 vs.0.94 +/- 0.18; p value = 0.010). There
      were no major complications. CONCLUSION: In our study, BMV had excellent
      immediate hemodynamic and clinical results inasmuch as MR severity increased only
      in some patients and, interestingly, decreased in a few. Our results, underscore
      BMV efficacy in severe MS. The echocardiographic calcification score was useful
      for identifying patients likely to have MR development or MR increase after BMV.

PMID- 25870628
TI  - Opium consumption and mid-term outcome of percutaneous coronary intervention in
      men.
AB  - BACKGROUND: Controversy persists over the potential benefits/harms of opium
      consumption in coronary heart disease. This study investigated the association
      between 12 months' major adverse cardiac events (MACE) and pre-procedural opium
      consumption among patients undergoing percutaneous coronary intervention (PCI).
      METHODS: Retrospectively, 1545 consecutive men who underwent PCI between 21(st)
      June 2009 and 20th June 2010 at Tehran Heart Center and were registered in the
      PCI Databank were entered into this cohort study. The occurrence of MACE, defined
      as cardiac death, non-fatal myocardial infarction, and need for target vessel
      revascularization (TVR) or target lesion revascularization (TLR), was compared
      between two groups of opium consumers and non-consumers in 350 (22.7%) patients.
      RESULTS: Sixty-four (0.86%) patients expired within 12 months. After adjustment
      for potential confounders, analysis revealed that opium consumption had no
      significant relationship with 12 months' MACE [11(3.1%) vs. 53(4.4%); p value =
      0.286, among opium users vs. non users, respectively].Furthermore, the different
      components of MACE, including target vessel revascularization, target lesion
      revascularization, coronary artery bypass graft, and non-fatal myocardial
      infarction, were not significantly related to opium use. CONCLUSION: Pre
      procedural opium usage in patients undergoing PCI was not associated with 12
      months' MACE.

PMID- 25870629
TI  - Comparison of the Effectiveness of Continuous versus Intermittent Cefazolin for
      the Prevention of Infection after Off-Pump Coronary Artery Bypass Graft.
AB  - BACKGROUND: Surgical site infection is known as a common complication after
      cardiac surgery, and Cefazolin is the best prophylactic antibiotic to prevent
      this complication. The goal of this study was to evaluate the effect of
      continuous and intermittent Cefazolin for the prevention of superficial surgical
      site infection following off-pump coronary artery bypass (OPCAB). METHODS: This
      prospective randomized clinical trial study was conducted on 141 patients
      candidated for OPCAB and divided into two groups. This study was performed
      between February 2011 and February 2012 in the Iranian city of Yazd. Patients in
      both groups received 2 g of Cefazolin as a starting dose and at 30 minutes before
      incision. Definition of surgical site infections was according to the Centers for
      Disease Control and Prevention Criteria (CDC-criteria). In the continuous
      infusion group (n = 74), 3 g of Cefazolin was infused over a 24-hour period after
      surgery. In the intermittent group (n = 67), 1 g of Cefazolin was administered at
      3, 11, and 19 hours after the starting dose. Hyperlipidemia, diabetes,
      hypertension, smoking, history of heart disease, and incidences of superficial
      infection were compared between the two groups. Duration of follow- up was 4
      weeks. RESULTS: The mean age of the patients was 60.49 +/- 10.63 years. The
      patients were 30.5% female and 69.5% male. There were no significant differences
      in age, body surface area, duration of operation, number of distal grafts, number
      of proximal grafts, and duration of hospital stay before heart surgery between
      two groups. The incidence of infection in intermittent group was (7.5%) and in
      continuous groups was (2.7%). There was no significant difference in the
      incidence of infection between the two groups (p value = 0.26). CONCLUSION: Our
      findings in this study showed no significant differences between continuous and
      intermittent Cefazolin for the prevention of superficial surgical site infections
      after OPCAB.

PMID- 25870630
TI  - Association between Sexual Function and Marital Relationship in Patients with
      Ischemic Heart Disease.
AB  - BACKGROUND: Patients with ischemic heart disease (IHD) may report difficulties
      with sexual function and marital relationship. However, there is a dearth of
      studies focusing on the association between these aspects in IHD patients. The
      present study sought to assess the association between sexual function and
      marital relationship among IHD patients and also test the effect modification of
      gender, education level, and marital distress on the above association. METHODS:
      In this cross-sectional study, 551 patients with IHD were enrolled and their
      sexual function and marital relationship quality were assessed with the Relation
      and Sexuality Scale (RSS) and Revised Dyadic Adjustment Scale (RDAS),
      respectively. Association between marital relationship quality and sexual
      function was assessed with respect to gender, education level, and marital
      distress. RESULTS: Most participants (72%) were men at a mean age of 57 +/- 11
      (range = 36-80) years. Total sexual function was significantly correlated with
      total marital quality (r = -0.28), marital consensus (r = -0.17), marital
      coherence (r = -0.19), marital affection expression (r = -0.22), and marital
      satisfaction (r = -0.25). Total marital quality also showed a significant
      association with sexual fear (r = -0.11). These associations were moderated by
      gender, education level, and marital distress level. CONCLUSION: Among the IHD
      patients, sexual function and marital relationship quality showed a mild to
      moderate association. Association between sexual function and marital
      relationship quality, however, may depend on gender, education level, and marital
      distress level.

PMID- 25870631
TI  - Pentalogy of fallot with a single coronary artery: a rare case report.
AB  - Anomalies of origin, course, and distribution of coronary arteries, including
      single coronary artery, are well known in patients with Tetralogy of Fallot.
      However, to the best of our knowledge, there is no published case report of
      Pentalogy of Fallot with a single coronary artery. Herein, we introduce a 22-year
      old female patient diagnosed via echocardiography and cardiac catheterization
      preoperatively as Pentalogy of Fallot with a single coronary artery arising from
      the left coronary sinus. 

PMID- 25870632
TI  - A case of double right coronary artery with separate ostium.
AB  - Coronary artery anomalies are rare, with their incidence varying from 1 to 5%.
      Angiography is a commonly used modality for the assessment of coronary artery
      anomalies. Based on previous reports, a majority of coronary artery anomalies are
      of origin or distribution, with separate ostia of the left anterior descending
      artery and left circumflex artery. Coronary artery anomalies may cause myocardial
      ischemia secondary to atherosclerosis in the same artery. We present a rare case
      of duplicated right coronary artery with a separate ostium, which caused
      myocardial ischemia. Our patient was a 51-year-old diabetic woman with typical
      chest pain and dyspnea on exertion. Electrocardiography showed left axis
      deviation, poor R progression, and biphasic T wave in the precordial leads.
      Echocardiography revealed left ventricular ejection fraction of 30-35% and global
      hypokinesia. Coronary angiography demonstrated three-vessel disease and a double
      ostial right coronary artery. We recommended coronary artery bypass graft
      surgery, but the patient refused it and we continued her treatment with anti
      ischemic drugs. 

PMID- 25870633
TI  - Biological glue application in repair of atrioventricular groove rupture: a case
      report.
AB  - Atrioventricular groove rupture is a rare, albeit mortal, complication following
      mitral valve surgery. Avoidance is the best strategy but it cannot fully prevent
      the occurrence of this complication. Several repair techniques have been
      described with varying success rates; however, the rarity of the complication
      precludes consensus about the safest technique. Here we report two cases of
      posterior atrioventricular groove rupture. Both cases were diagnosed immediately
      after the cessation of cardiopulmonary bypass. Repair was performed successfully
      with a technique involving the use of biological glue. The postoperative course
      was uneventful for both of them. Both cases are well with normally functioning
      mitral prostheses; one with a follow-up time of 5.5 years and the other 10
      months. We believe that the glue provides additional hemostasis and support to
      the repaired area. 

PMID- 25870634
TI  - Difficult management of coronary artery disease in a patient with thrombotic
      thrombocytopenic purpura.
AB  - Thrombotic thrombocytopenic purpura (TTP) is a rare syndrome affecting multiple
      organs. There is no sufficient evidence regarding the clinical cardiac
      manifestations of TTP. Nonetheless, pathologic cardiac involvement is quite
      frequent in acute TTP, which is predominantly manifested as myocardial necrosis
      due to coronary arteriolar microthrombosis. The present case report describes a
      43-year-old man with long-standing remitted TTP, who suffered from a sequence of
      refractory thrombotic epicardial coronary events. Aggressive medical and
      interventional therapies, including long-term dual antiplatelets and coronary
      angioplasty, were finally successful in remitting the thrombotic events. During
      his two-year follow up, he has been asymptomatic. 

PMID- 25870635
TI  - Incidentally detected tricuspid papillary fibroelastoma.
AB  - A 56-year-old man was admitted to our hospital for coronary artery bypass graft
      surgery. Preoperative transthoracic echocardiography revealed thickening of the
      anterior leaflet of the tricuspid valve, and transesophageal echocardiography
      showed oval and irregular-shaped masses, featuring well-demarcated borders and a
      homogenous texture, attached to the atrial side of the anterior leaflet of the
      tricuspid valve with a small, tiny, mobile stalk. In the operating room, this
      mass was resected and gross anatomical examination showed multiple finger-like
      fronds attached to the stalk. When it was placed in saline, the mass revealed
      typical "sea anemone", suggestive of papillary fibroelastoma. Although
      echocardiography had been previously conducted for routine preoperative
      evaluation, this incidental finding significantly changed the surgical plan. 

PMID- 25870636
TI  - Is the diagnostic value of electrocardiography for the measurement of left
      ventricular mass index underestimated?

PMID- 25870637
TI  - Is the diagnostic value of electrocardiography for the measurement of left
      ventricular mass index underestimated? Reply.

PMID- 25870638
TI  - Correlation between Mitral Regurgitation and Myocardial Mechanical Dyssynchrony
      and QRS Duration in Patients with Cardiomyopathy.
AB  - BACKGROUND: Several competing geometric and hemodynamic factors are suggested as
      contributing mechanisms for functional mitral regurgitation (MR) in heart failure
      patients. We aimed to study the relationships between the severity of MR and the
      QRS duration and dyssynchrony markers in patients with ischemic or dilated
      cardiomyopathy. METHODS: We prospectively evaluated 251 heart failure patients
      with indications for echocardiographic evaluation of possible cardiac
      resynchronization therapy. All the patients were subjected to transthoracic
      echocardiography and tissue Doppler imaging to evaluate the left ventricular (LV)
      synchronicity. The patients were divided into two groups according to the
      severity of MR: <= mild MR and >= moderate MR. The effects of different
      dyssynchrony indices were adjusted for global and regional left ventricular
      remodeling parameters. RESULTS: From the 251 patients (74.5% male, mean age =
      53.38 +/- 16.68 years), 130 had <= mild MR and 121 had >= moderate MR. There were
      no differences between the groups regarding the mean age, frequency of sex, and
      etiology of cardiomyopathy. The LV systolic and diastolic dimensions were greater
      in the patients with >= moderate MR (all p values < 0.001). Among the different
      echocardiographic factors, the QRS duration (150.75 +/- 34.66 vs. 126.77 +/-
      29.044 ms; p value = 0.050) and interventricular mechanical delay (41.60 +/-
      29.50 vs. 35.00 ms +/- 22.01; p value = 0.045) were significantly longer in the
      patients with <= mild MR in the univariate analysis. After adjusting the effect
      of these parameters on the severity of MR for the regional and global LV
      remodeling parameters, no significant impact of the QRS duration and dyssynchrony
      indices was observed. CONCLUSION: Our results showed that the degree of
      functional MR was not associated with the QRS duration and inter- and
      intraventricular dyssynchrony in our patients with cardiomyopathy. No association
      was found between the severity of MR and the ischemic or dilated etiology for
      cardiomyopathy.

PMID- 25870639
TI  - Radiofrequency atrial fibrillation ablation technique in patients with mitral
      valve surgery and left atrial reduction procedures.
AB  - BACKGROUND: About half of all patients who undergo mitral valve surgery suffer
      from atrial fibrillation (AF). Cox described the surgical cut-and-sew Maze
      procedure, which is an effective surgical method but has some complications. This
      study was designed to evaluate the efficacy of a substitution method of
      radiofrequency ablation (RFA) for patients undergoing mitral valve surgery with
      AF. METHODS: We evaluated 50 patients, comprising 40 men and 10 women at a mean
      age of 61.8 +/- 7.5 years, who underwent mitral valve surgery with RFA between
      March 2010 and August 2013. All the patients had permanent AF with an enlarged
      left atrium (LA). The first indication for surgery was underlying organic
      lesions. Mitral valve replacement or repair was performed in the patients as a
      single procedure or in combination with aortic valve replacement or coronary
      artery bypass grafting. Radiofrequency energy was used to create continuous
      endocardial lesions mimicking most incisions and sutures. We evaluated the pre-
      and postoperative LA size, duration of aortic cross-clamping, cardiopulmonary
      bypass time, intensive care unit stay, and total hospital stay. RESULTS: The mean
      preoperative and postoperative LA sizes were 7.5 +/- 1.4 cm and 4.3 +/- 0.7 cm (p
      value = 0.0001), respectively. The mean cardiopulmonary bypass time and the
      aortic cross-clamping time were 134.3 +/- 33.7 minand 109.0 +/- 28.4 min,
      respectively. The average stay at the intensive care unit was 2.1 +/- 1.2 days,
      and the total hospital stay was 8.3 +/- 2.4 days. Rebleeding was the only
      complication, found in one patient. There was no early or late mortality. Eighty
      two percent of the patients were discharged in normal sinus rhythm. Five other
      patients had normal sinus rhythm at 6months' follow-up, and the remaining 4
      patients did not have a normal sinus rhythm after 6 months. CONCLUSION:
      Radiofrequency ablation, combined with LA reduction, is an effective option for
      the treatment of permanent AF concomitant with mitral valve surgery.

PMID- 25870640
TI  - Frequency of ischemic mitral regurgitation after first-time acute myocardial
      infarction and its relation to infarct location and in-hospital mortality.
AB  - BACKGROUND: Ischemic mitral regurgitation (IMR) is a common complication after
      acute myocardial infarction (AMI). We aimed to investigate the frequency of IMR
      following first-time AMI and its association with infarct location, in-hospital
      mortality, and complications. METHODS: From September 2011 to November 2012, all
      patients with a diagnosis of first-time acute ST-elevation MI were enrolled in
      the study. Patients with previous MI and heart failure, organic mitral valve
      disorders, and previous mitral surgery were excluded from the study. The
      patients' baseline characteristic, echocardiographic parameters, and
      complications were recorded. The frequency of IMR after AMI and its relation to
      infarct location and in-hospital mortality were evaluated. RESULTS: Altogether,
      250 patients (180 male) at a mean age of 60.21 +/- 12.90 years were studied. IMR
      was detected in 114 (45%) patients. There was no association between the presence
      of MR and gender, systemic hypertension, smoking, diabetes mellitus, or body mass
      index; however, serum LDL-cholesterol and triglyceride levels were significantly
      higher in the patients with IMR . The most frequent territory of MI was anterior
      in the patients without MR, while the anterolateral territory was the most common
      one in the patients with IMR. The patients with IMR had more reduced left
      ventricular ejection fraction, more elevated left ventricular end-diastolic
      pressure, and higher pulmonary arterial pressure (p values < 0.001, < 0.001, and
      < 0.001, respectively). Stage III diastolic dysfunction was more frequent in the
      patients with IMR. All the deaths occurred in the IMR patients, who also had more
      complicated AMI. CONCLUSION: IMR following AMI is highly prevalent, and it
      complicates about half of the patients. Regarding its relation to the AMI
      complications, assessment of the MR severity is necessary to make an appropriate
      decision for treatment.

PMID- 25870641
TI  - Comparison between QT Interval Parameters in Type 2 Diabetic and Nondiabetic
      Patients with Non-ST Elevation Myocardial Infarction.
AB  - BACKGROUND: QT interval parameters have been suggested as a predictor of lethal
      arrhythmia and mortality in patients with myocardial infarction. The aim of the
      present study was to compare the value of QT interval indices in patients
      presenting with non-ST-segment elevation myocardial infarction (NSTEMI) between a
      group of patients with type 2 diabetes mellitus and a nondiabetic group of
      patients. METHODS: This case-control study evaluated QT interval parameters in
      115 patients (47 diabetic and 68 nondiabetic patients) diagnosed with NSTEMI
      between September 2011 and July 2012. The following QT interval indices were
      analyzed: maximum (max) and minimum (min) QT interval; max and min corrected QT
      interval (QTc); QT dispersion (QTd); and corrected QT dispersion (QTcd). All the
      patients were observed for ventricular arrhythmia during their hospital course
      and underwent coronary angiography. They were selected to undergo coronary artery
      bypass surgery (CABG) or percutaneous coronary angioplasty (PCI) based on their
      coronary anatomy. RESULTS: The mean age of the patients was 60.8 +/- 11.4 years.
      The patients were 40.0% female and 60.0% male. There were no significant
      differences in clinical characters between type 2 diabetic and nondiabetic
      patients with NSTEMI. Compared with post-myocardial infarction patients without
      diabetes, those with type 2 diabetes had higher QTc max, QTd and QTcd (p value <
      0.05). There was a significant difference in QTd and QTcd in the patients needing
      coronary revascularization with diabetes as opposed to the nondiabetics (p value
      = 0.035 and p value = 0.025, respectively) as well as those who had ventricular
      arrhythmia with diabetes (p value = 0.018 and p value = 0.003, respectively).
      QTcd was higher in the patients who had higher in-hospital mortality (p value =
      0.047). The QTc max, QTd and QTcd were significantly (all p values < 0.05)
      associated with ventricular arrhythmia, QTcd with need for revascularization and
      QTc max with in-hospital mortality in the diabetic patients. CONCLUSION: Based on
      the findings of this study, it seems that type 2 diabetics with NSTEMI have
      greater QTc max, QTd, and QTcd and these QT parameters may have a relationship
      with worse cardiac outcomes and poorer prognoses.

PMID- 25870642
TI  - Ankle-Brachial Index as a Prognostic Factor and Screening Tool in Coronary Artery
      Disease: Does it Work?
AB  - BACKGROUND: Given the lack of consistency in the literature regarding the
      reliability of the ankle-brachial index (ABI) as a valid screening tool and an
      independent risk indicator of cardiovascular events and mortality, we compared it
      with angiography as a reference standard test. METHODS: This case-control study,
      conducted between 2010 and 2011 in Tehran Heart Center, recruited 362
      angiographically confirmed cases of coronary artery disease (CAD) and 337
      controls. A standard protocol was used to measure the ABI and different CAD risk
      factors. RESULTS: A low ABI had specificity of 99.7%, positive predictive value
      of 95.8%, negative predictive value of 49.8%, sensitivity of 64%, likelihood
      ratio of 24.07, and odds ratio (OR) of 22.79 (95%CI: 3.06-69.76). The role of the
      associated risk factors was evaluated with OR (95%CI), with the variables
      including gender 3.15 (2.30-4.30), cigarette smoking 2.72 (1.86-3.99), family
      history 1.72 (1.17-2.51), diabetes 1.66 (1.15-2.4), and dyslipidemia 1.38 (1.02
      1.88). In a multivariate model, the following variables remained statistically
      significantly correlated with CAD [OR (95%CI)]: ABI 13.86 (1.78-17.62); gender
      3.69 (2.43-5.58); family history of CAD 2.18 (1.41-3.37); smoking 1.69 (1.08
      2.64); age 1.04 (1.02-1.06). CONCLUSIONS: A low ABI had specificity of 99.7%;
      however, because of its low sensitivity (64%), we should consider CAD risk
      factors associated with a low ABI in order to use it as a first-line screening
      test.

PMID- 25870643
TI  - Endovascular Repair of Supra-Celiac and Abdominal Aortic Pseudo Aneurysms
      Concomitant with a Right Atrial Mass in a Patient with Behcet's Disease: A Case
      Report.
AB  - Behcet's disease is a rare immune mediated systemic vasculitis which besides it's
      more frequent involvement of eyes and skin, sometimes present with aortic pseudo
      aneurysm and more rarely cardiac inflammatory masses.A 51-year-old patient with
      Behcet's Disease presented with two symptomatic aortic pseudoaneurysms
      concomitant with a right atrial mass. Computed tomography (CT) revealed one supra
      celiac and another infrarenal aortic pseudoaneurysms. Echocardiography showed a
      large mobile mass in the right atrium. Both pseudoaneurysms were successfully
      excluded simultaneously via endovascular approach with Zenith stent-grafts, and
      the atrial mass was surgically removed 10 days later. Post-implant CT showed
      successful exclusion of both pseudo-aneurysms, patency of all relevant arteries,
      and patient is now asymptomatic and has returned to normal lifestyle. Multiple
      pseudoaneurysms concomitant with a right atrial mass can be an initial
      manifestation of Behcet's disease. Endovascular repair can be a good treatment
      option for the pseudoaneurysms. 

PMID- 25870644
TI  - A rare case of right-sided heart failure after bentall procedure.
AB  - Pseudoaneurysms of the ascending aorta, which are rare and life-threatening
      complications in cardiovascular surgeries, can be caused by the Bentall
      procedure. We describe a 44-year-old woman, who had a medical history of acute
      aortic dissection (Type A) and the Bentall procedure and was admitted because of
      exertional dyspnea, edema of the lower extremities, ascites, and holosystolic
      murmur in the left lower sternal border. Preoperative echocardiography revealed a
      pseudoaneurysm of the ascending aorta and fistulization of the pseudoaneurysm to
      the right atrium. Multi-slice computed tomographic scan also showed a large
      pseudoaneurysm of the ascending aorta around the tube graft. The patient
      underwent surgery, during which the pseudoaneurysm was resected, the ostium of
      the right coronary artery was reimplanted, and the orifice of the right atrial
      fistula was sutured. Intraoperative transesophageal echocardiography revealed the
      perfect result of the surgery. The patient was discharged uneventfully. 

PMID- 25870645
TI  - Central venous line and acute neurological deficit: a case series.
AB  - Central venous catheter (CVC) insertion is a practical way to assess patients
      hemodynamic specially in cardiovascular surgery but this relatively simple junior
      level procedure is not risk free and its common reported complications include;
      pneumothorax, hydrothorax, hemothorax, local hematoma, cardiac tamponade,
      vascular injury, thrombosis, embolism, and catheter disruption. Here in this
      article we are going to present 6 patients with very unusual presentation of CVC
      complication which was neurological deficit presented by agitation,
      unconsciousness, disorientation to time and place and hemiparesis. All patients
      undergone neurologic consult and brain computed tomography. Final diagnosis was
      brain ischemic damage and finally we kept them on conservative management;
      fortunately we did not have any permanent damage. 

PMID- 25870646
TI  - A rare case of large left atrial myxoma associated with carney syndrome.
AB  - Carney Syndrome (CS) is an autosomal dominant multiple neoplasia syndrome that
      includes cardiac, endocrine, cutaneous, and neural tumors. Cardiac myxomas can be
      seen in the course of CS. A 46-year-old female patient was admitted to our clinic
      with palpitation, cough, and exertional dyspnea. Physical examination revealed
      pigmented lesions, especially scattered in the neck, chest, and extremities.
      Echocardiography revealed a left atrial mass, 6 * 4 cm in size, originating from
      the interatrial septum that was protruding into the left ventricle through the
      mitral valve during diastole. The tumor was excised from the interatrial septum
      with its pedicle. The patient was discharged at the fifth postoperative day
      without any complication. Cardiac myxomas are a cornerstone of this disease since
      cardiac manifestations and related complications account for the majority of
      mortality seen in the course of CS. 

PMID- 25870647
TI  - Left atrial appendage thrombosis simulating myxoma.

PMID- 25870648
TI  - Comparative study of subcortical atrophy in patients with frontotemporal dementia
      and dementia with extrapyramidal signs.
AB  - OBJECTIVES: To investigate the severity of subcortical atrophy in frontotemporal
      dementia (FTD) without extrapyramidal symptoms (EPS) and dementia with EPS. In
      addition, we aim to verify if there is correlation between demographic and
      clinical characteristics and subcortical atrophy in the groups. Methodology : The
      sample was composed of 21 patients with dementia and EPS as well as 19 patients
      with FTD without EPS. A linear assessment was conducted in order to identify the
      degree of subcortical atrophy (i.e., bifrontal index - BFI) using MRI. Moreover,
      the Mini-Mental State Examination (MMSE), Pfeffer Functional Activities
      Questionnaire (FAQ) and the Clinical Dementia Rating (CDR) were used to
      investigate clinical aspects. Results : It was verified that patients with
      dementia and EPS was older than the patients with FTD (p=0.01). The severity of
      cognitive deficits was associated with BFI, as well as the dementia severity in
      the EPS group. Conclusion : FTD group presented mean BFI scores above the cutoff
      for normal elderly population, indicating the presence of subcortical atrophy in
      this group. Mean BFI was higher (although not statistically significant) in FTD
      group than in dementia with EPS, which can suggest at least that subcortical
      pathology in FTD may be as important as in the dementia with EPS group.
      Subcortical atrophy is a good biological marker for cognitive deterioration in
      FTD and in dementia with EPS.

PMID- 25870649
TI  - Should Unexplained Painful Physical Symptoms be Considered within the Spectrum of
      Depressive Symptoms?
AB  - OBJECTIVE: To examine whether painful physical symptoms (PPS) can be considered
      within the spectrum of depressive symptoms. METHODS: Data for this post-hoc
      analysis were taken from a 6-month observational study mostly conducted in East
      Asia, Mexico, and the Middle East of 1,549 depressed patients without sexual
      dysfunction at baseline. Both explanatory and confirmatory factor analyses (EFA
      and CFA) were performed on the combined items of the 16-item Quick Inventory of
      Depressive Symptomatology Self-Report and the Somatic Symptom Inventory (seven
      pain-related items only). An additional second-order CFA was also conducted to
      examine an association between retained factors and the overall "depressive
      symptoms" factor. In addition, Spearman's correlation was used to assess levels
      of correlation between retained factors and depression severity as well as
      quality of life. RESULTS: Both EFA and CFA suggested and validated a four-factor
      solution, which included a pain factor. The other three factors identified were a
      mood/cognitive factor, a sleep disturbance factor, and an appetite/weight
      disturbance factor. All four factors were significantly associated with the
      overall factor of depression. They were also highly correlated to depression
      severity and quality of life (p<0.001 for all). The levels of correlations with
      the pain factor were generally greater than those with the appetite/weight factor
      and similar to those with the sleep factor. CONCLUSION: It may be reasonable to
      consider PPS within a broad spectrum of depressive symptoms. At least, they
      should be routinely assessed in patients with depression. Further research is
      warranted to validate these preliminary findings.

PMID- 25870650
TI  - Quantifying spatial heterogeneity of chlorophyll fluorescence during plant growth
      and in response to water stress.
AB  - BACKGROUND: Effects of abiotic and biotic stresses on plant photosynthetic
      performance lead to fitness and yield decrease. The maximum quantum efficiency of
      photosystem II (F v/F m) is a parameter of chlorophyll fluorescence (ChlF)
      classically used to track changes in photosynthetic performance. Despite recent
      technical and methodological advances in ChlF imaging, the spatio-temporal
      heterogeneity of F v/F m still awaits for standardized and accurate
      quantification. RESULTS: We developed a method to quantify the dynamics of
      spatial heterogeneity of photosynthetic efficiency through the distribution-based
      analysis of F v/F m values. The method was applied to Arabidopsis thaliana grown
      under well-watered and severe water deficit (survival rate of 40%). First, whole
      plant F v/F m shifted from unimodal to bimodal distributions during plant
      development despite a constant mean F v/F m under well-watered conditions. The
      establishment of a bimodal distribution of F v/F m reflects the occurrence of two
      types of leaf regions with contrasted photosynthetic efficiency. The distance
      between the two modes (called S) quantified the whole-plant photosynthetic
      heterogeneity. The weighted contribution of the most efficient/healthiest leaf
      regions to whole-plant performance (called W max) quantified the spatial
      efficiency of a photosynthetically heterogeneous plant. Plant survival to water
      deficit was associated to high S values, as well as with strong and fast recovery
      of W max following soil rewatering. Hence, during stress surviving plants had
      higher, but more efficient photosynthetic heterogeneity compared to perishing
      plants. Importantly, S allowed the discrimination between surviving and perishing
      plants four days earlier than the mean F v/F m. A sensitivity analysis from
      simulated dynamics of F v/F m showed that parameters indicative of plant
      tolerance and/or stress intensity caused identifiable changes in S and W max.
      Finally, an independent comparison of six Arabidopsis accessions grown under well
      watered conditions indicated that S and W max are related to the genetic
      variability of growth. CONCLUSIONS: The distribution-based analysis of ChlF
      provides an efficient tool for quantifying photosynthetic heterogeneity and
      performance. S and W max are good indicators to estimate plant survival under
      water stress. Our results suggest that the dynamics of photosynthetic
      heterogeneity are key components of plant growth and tolerance to stress.

PMID- 25870651
TI  - Properties and kinetics of microRNA regulation through canonical seed sites.
AB  - MicroRNAs are a fundamental class of small RNAs involved in post-transcriptional
      gene regulation; however, the mechanism by which microRNAs regulate their gene
      targets in animals remains poorly understood. Practically, a mechanistic
      understanding of microRNA binding and regulation is crucial for the rational
      design of microRNA-based vectors for RNA interference. In this report, we focus
      on the largest known class of microRNA targets, the canonical seed targets, and
      explore the factors involved in modulating target downregulation in vivo at the
      protein level. Using an in vivo sensor assay in the ascidian Ciona intestinalis,
      we quantify miR-124-mediated downregulation of 38 canonical seed targets cloned
      from the Ciona genome as well as 10 control non-targets. Supporting previous
      findings, we observed that the seed type and number of seed sites are correlated
      with downregulation. However, up to a 50% variation in downregulation levels was
      observed for targets within the same seed class, indicating a role of non-seed
      factors in modulating downregulation. Although we did not observe a significant
      correlation of previously reported non-seed determinants with downregulation
      levels at saturation in our assay, our data suggest that two previously
      identified factors, secondary structure and 3'end complementarity, may play a
      role in the initial kinetics of microRNA-target binding. Importantly, using
      different concentrations of miR-124 we show that dose-dependent target
      downregulation profiles follow Michaelis-Menten kinetics. In summary, our
      findings emphasize the importance of non-seed factors as well as the importance
      of cellular concentrations of microRNAs relative to their targets when studying
      the mechanisms of endogenous microRNA regulation. 

PMID- 25870652
TI  - Grading operative findings at laparoscopic cholecystectomy- a new scoring system.
AB  - INTRODUCTION: Variation in outcomes from surgery is a major challenge and
      defining surgical findings may help set benchmarks, which currently do not exist
      in laparoscopic cholecystectomy. This study outlines a new surgical scoring
      system incorporating key operative findings. METHODS: English language studies
      (from January 1965 to July 2014) pertaining to severity scoring and predictors of
      difficult laparoscopic cholecystectomy were searched for in PubMed, Embase and
      Cochrane databases using the search terms 'Laparoscopic cholecystectomy or Lap
      chole' and/or 'Scoring Index or Grading system or Prediction of difficulty or
      Conversion to open' in various combinations. Cross-referencing from papers
      retrieved in the original search identified additional articles. RESULTS: Sixteen
      published papers report a gallbladder (GB) scoring system, but all relate to pre
      operative clinical and imaging findings, rather than operative findings. The
      current scoring system, using operative findings incorporates the appearance of
      the GB, presence of GB distension, ease of access, potential biliary
      complications and time taken to identify cystic duct and artery. A score of <2
      would imply mild difficulty, 2-4 moderate, 5-7 severe and 8-10 extreme.
      CONCLUSION: This paper reports one of the first operative classifications of
      findings at laparoscopic cholecystectomy. It has the potential to allow
      benchmarks for international collaboration of operative and patient outcomes in
      patients undergoing laparoscopic cholecystectomy.

PMID- 25870653
TI  - Impact of the supramolecular structure of cellulose on the efficiency of
      enzymatic hydrolysis.
AB  - BACKGROUND: The efficiency of enzymatic hydrolysis is reduced by the structural
      properties of cellulose. Although efforts have been made to explain the mechanism
      of enzymatic hydrolysis of cellulose by considering the interaction of
      cellulolytic enzymes with cellulose or the changes in the structure of cellulose
      during enzymatic hydrolysis, the process of cellulose hydrolysis is not yet fully
      understood. We have analysed the characteristics of the complex supramolecular
      structure of cellulose on the nanometre scale in terms of the spatial
      distribution of fibrils and fibril aggregates, the accessible surface area and
      the crystallinity during enzymatic hydrolysis. Influence of the porosity of the
      substrates and the hydrolysability was also investigated. All cellulosic
      substrates used in this study contained more than 96% cellulose. RESULTS:
      Conversion yields of six cellulosic substrates were as follows, in descending
      order: nano-crystalline cellulose produced from never-dried soda pulp (NCC-OPHS
      ND) > never-dried soda pulp (OPHS-ND) > dried soda pulp (OPHS-D) > Avicel >
      cotton treated with sodium hydroxide (cotton + NaOH) > cotton. CONCLUSIONS: No
      significant correlations were observed between the yield of conversion and
      supramolecular characteristics, such as specific surface area (SSA) and lateral
      fibril dimensions (LFD). A strong correlation was found between the average pore
      size of the starting material and the enzymatic conversion yield. The degree of
      crystallinity was maintained during enzymatic hydrolysis of the cellulosic
      substrates, contradicting previous explanations of the increasing crystallinity
      of cellulose during enzymatic hydrolysis. Both acid and enzymatic hydrolysis can
      increase the LFD, but no plausible mechanisms could be identified. The sample
      with the highest initial degree of crystallinity, NCC-OPHS-ND, exhibited the
      highest conversion yield, but this was not accompanied by any change in LFD,
      indicating that the hydrolysis mechanism is not based on lateral erosion.

PMID- 25870654
TI  - An integrated approach for efficient biomethane production from solid bio-wastes
      in a compact system.
AB  - BACKGROUND: Solid bio-wastes (or organic residues) are worldwide produced in high
      amount and increasingly considered bioenergy containers rather than waste
      products. A complete bioprocess from recalcitrant solid wastes to methane (SW2M)
      via anaerobic digestion (AD) is believed to be a sustainable way to utilize solid
      bio-wastes. However, the complex and recalcitrance of these organic solids make
      the hydrolysis process inefficient and thus a rate-limiting step to many AD
      technologies. Effort has been made to enhance the hydrolysis efficiency, but a
      comprehensive assessment over a complete flow scheme of SW2M is rare. RESULTS: In
      this study, it comes to reality of a complete scheme for SW2M. A novel process to
      efficiently convert organic residues into methane is proposed, which proved to be
      more favorable compared to conventional methods. Brewers' spent grain (BSG) and
      pig manure (PM) were used to test the feasibility and efficiency. BSG and PM were
      enzymatically pre-hydrolyzed and solubilized, after which the hydrolysates were
      anaerobically digested using different bioreactor designs, including expanded
      granular sludge bed (EGSB), continuously stirred tank reactor (CSTR), and
      sequencing batch reactor (SBR). High organic loading rates (OLRs), reaching 19
      and 21 kgCOD . m(-3) . day(-1) were achieved for the EGSBs, fed with BSG and PM,
      respectively, which were five to seven times higher than those obtained with
      direct digestion of the raw materials via CSTR or SBR. About 56% and 45% organic
      proportion of the BSG and PM can be eventually converted to methane. CONCLUSIONS:
      This study proves that complex organic solids, such as cellulose, hemicellulose,
      proteins, and lipids can be efficiently hydrolyzed, yielding easy
      biodegradable/bio-convertible influents for the subsequent anaerobic digestion
      step. Although the economical advantage might not be clear, the current approach
      represents an efficient way for industrial-scale treatment of organic residues
      with a small footprint and fast conversion of AD.

PMID- 25870655
TI  - Alpha-synucleinopathy and neuropsychological symptoms in a population-based
      cohort of the elderly.
AB  - INTRODUCTION: Studies with strong selection biases propose that alpha
      synucleinopathy (AS) spreads upwards and downwards in the neuraxis from the
      medulla, that amygdala-dominant AS is strongly associated with Alzheimer's
      disease (AD), and that a more severe involvement of the cerebral cortex is
      correlated with increasing risk of dementia. This study examines the association
      of AS patterns and observed neuropsychological symptoms in brains of a population
      representative donor cohort. METHODS: Brains donated in 2 out of 6 cognitive
      function and ageing study cohorts (Cambridgeshire and Nottingham) were examined.
      Over 80% were >80 years old at death. The respondents were evaluated
      prospectively in life for cognitive decline and dementia. Immunocytochemistry for
      tau and alpha-synuclein (using LB509 by Zymed Laboratories) was carried out in
      208 brains to establish Braak stage and the pattern and severity of AS following
      the dementia with Lewy bodies (DLB) consensus recommendations. Dementia, specific
      neuropsychological measures as measured using the Cambridge cognitive
      examination, the presence of hallucinations and Parkinson's disease were
      investigated. RESULTS: Four patterns of AS were observed: no AS pathology (n =
      92), AS pathology following the DLB consensus guidelines (n = 33, of which five
      were 'neocortical'), amygdala-predominant AS (n = 18), and other AS patterns (n =
      33). Each group was subdivided according to high/low neurofibrillary tangles
      (NFT) Braak stage. Results showed no association between dementia and these
      patterns of AS, adjusting for the presence of NFT or not. The risk of visual
      hallucinations shows a weak association with AS in the substantia nigra (odds
      ratio (OR) = 3.2; 95% confidence interval (CI) 0.5 to 15.5; P = 0.09) and
      amygdala (OR = 3.0; 95% CI 0.7 to 12.3; P = 0.07). The analysis is similar for
      auditory hallucinations in subcortical regions. CONCLUSIONS: Among the whole
      population of older people, AS does not increase the risks for dementia,
      irrespective of Braak stage of NFT pathology. There was no evidence that the
      pattern of AS pathology in cortical areas was relevant to the risk of
      hallucination. In general, the hypothesis that AS as measured using these methods
      per se is a key determinant of cognitive clinical phenotypes is not supported.

PMID- 25870656
TI  - Statins and memory loss: An Australian experience.
AB  - BACKGROUND: Statins are a first-line drug treatment for hypercholesterolaemia.
      Recently there has been general public and media interest surrounding uses and
      side effects of statins, including memory loss. AIMS: We analysed an Australian
      experience in statin usage in an attempt to improve understanding of the
      relationship between statins and memory-related adverse events. METHODS: Total
      adverse events (TAE) and adverse events with single suspected medicines (SSM) for
      memory loss and other memory-related adverse events were searched for statin
      compounds from January 1992 to May 2013, using the Medicare Australia and
      Pharmaceutical Benefits Scheme (PBS) websites and Therapeutic Goods
      Administration (TGA) adverse events data. TAE and SSM were compared to the number
      of prescriptions by item number searched using the PBS. The process was repeated
      for non-statin cholesterol-lowering drugs. RESULTS: The most common adverse event
      was amnesia (167 events for statins and six for non-statins). There were 239 TAE
      (incidence rate=0.88) listed for statins and 10 for non-statins (incidence
      rate=0.53). There were 217 SSM events listed for the statins (incidence rate =
      0.08) and eight for the alternatives (incident rate=0.04). The differences
      between TAE and SSM incidence rates between statins and non-statins drugs were
      not significant (both p values >0.05). CONCLUSION: We found that there were no
      differences in memory-related adverse events between statins and other
      cholesterol-lowering medications using Australian PBS and TGA adverse events
      data.

PMID- 25870657
TI  - Rasmussen's encephalitis: A case report.
AB  - Rasmussen's encephalitis (RE) is a rare neurological disorder of inflammatory
      aetiology characterised by encephalitis, intractable seizures, hemiparesis,
      variable motor deficits, and dementia. It is not commonly considered in the
      clinical differential diagnosis of a patient with a past history of a stroke-like
      episode presenting with status epilepticus. It is suspected mainly in children in
      whom the disease is more common. Here we report a case of an adult man presenting
      with a common symptom of seizure caused by Rasmussen's encephalitis. 

PMID- 25870658
TI  - Giant sigmoid diverticulum: A case report.
AB  - Sigmoid colon diverticulosis is commonly seen in both the surgical outpatient and
      emergency departments. Rarely, these sigmoid diverticulum, which usually range
      from 2-3mm to 2cm in size, can enlarge to more than 10 times. This is due to a
      ball-valve type mechanism that traps colonic gas inside the sigmoid diverticulum
      causing it to gradually enlarge. Patients with a giant sigmoid diverticulum (GSD)
      must be investigated thoroughly as two per cent of patients will present with a
      colonic carcinoma either within or distal to the GSD. Clinical symptoms of a GSD
      can range from chronic abdominal pain, altered bowel habits, abdominal
      distention, weight loss, bleeding, perforation, fistula formation, or bowel
      obstruction. CT and plain abdominal x-ray is the investigation of choice for its
      diagnosis. Barium enema is useful to determine the presence of a carcinoma within
      the GSD. Sigmoidoscopy is useful to rule out a distal colonic carcinoma. This is
      the first published case where nocturnal diarrhoea is the primary differentiating
      symptom in the patient. The treatment of choice for a GSD is complete resection
      of the diverticulum and/or the adjacent sigmoid colon. This can be performed with
      a primary anastomosis or a double-stage procedure. 

PMID- 25870659
TI  - Polyarthritis and massive small bowel bleed: An unusual combination in scrub
      typhus.
AB  - Scrub typhus is an acute febrile illness caused by the intracellular parasite
      Orientia tsutsugamushi. Although most cases present with mild symptoms and signs
      and recover spontaneously, some cases can be severe with multi-organ dysfunction
      and a protracted course, which may be fatal if left untreated. Apart from fever
      and constitutional symptoms, atypical presentations allow this disease to mimic
      several common conditions. We report a case of scrub typhus in an 18-year-old
      male who presented with severe polyarthritis involving all large joints and a
      massive lower gastrointestinal bleed from ulcers in the terminal ileum, secondary
      to vasculitis in the small bowel. This combination of pathologies has not
      previously been reported in cases of scrub typhus. The patient improved following
      surgical intervention and specific anti-rickettsial therapy with azithromycin. 

PMID- 25870660
TI  - Scombroid fish poisoning illness and coronary artery vasospasm.
AB  - We present an interesting case of a young man with coronary artery vasospasm
      complicating scombroid fish poisoning illness. The initial presentation included
      tachycardia and significant hypotension. A 12-lead ECG showed sinus tachycardia
      with marked widespread ST segment depression and ST elevation in aVR. Symptoms
      subsequently improved with intravenous fluid rehydration, antihistamines, and
      glyceral trinitrate. The underlying pathogenesis and treatment of this rarely
      described manifestation of the fish poisoning illness is discussed. 

PMID- 25870661
TI  - A rare case of lactation anaphylaxis.
AB  - Lactation anaphylaxis (LA) is an extremely rare condition with only five other
      cases having been previously reported in the literature. Patients will exhibit
      cutaneous symptoms, respiratory symptoms, gastrointestinal symptoms, and/or
      cardiovascular symptoms. Post-partum, the drop in hormones is thought to
      facilitate an exaggerated histamine response. An elevated serum tryptase level
      performed between 15 minutes to three hours of onset of symptoms will confirm a
      true anaphylactic reaction. It is important to be aware of this extremely rare
      medical condition and its management with antihistamines. Better awareness and
      education of medical staff on this very rare phenomenon can help to better manage
      these patients. 

PMID- 25870662
TI  - The evolution of cochlear implant technology and its clinical relevance.
AB  - The article presents a brief history of the development of the cochlear implant,
      from its beginnings to the present day. After a short description of the device,
      it describes the evolution of the technology for three of the top manufacturing
      companies, from the first model marketed, to the latest. It presents the
      technological advancements from one model to the next, taking into account the
      exterior design, processing capabilities and functionality. 

PMID- 25870663
TI  - Benefits of anterior chamber paracentesis in the management of glaucomatous
      emergencies.
AB  - Anterior chamber paracentesis (ACP) is an alternative technique to reduce
      intraocular pressure (IOP) in patients with acute closed-angle glaucoma (ACAG)
      and requires controlled drainage of aqueous humor from the anterior chamber using
      a needle or an incision paracentesis with a knife. PURPOSE: Evaluation of
      efficacy and safety of AC paracentesis in acute increases of intraocular
      pressure. METHOD: This was an observational study done on a group of 24 patients
      with acute, unilateral increases of IOP> 50mmHg. IOP was measured before, 10
      minutes, 1 day, 7 days and 30 days after ACP using applanation tonometry.
      RESULTS: Intraocular pressure decreased from an average of 52.5 mmHg to 25.5 mmHg
      to 17.5 mmHg at 10 minutes and 7 days from the ACP. Anterior chamber paracentesis
      combined with glaucoma medication led to the cessation of symptoms in all
      patients included in the lot and the resolution of corneal edema in 20 cases.
      CONCLUSION: ACP is safe and effective in acute increases of IOP in the acute form
      of the primary angle closure glaucoma but remains an adjunct to conventional
      therapy drug.

PMID- 25870664
TI  - Implant surgery in healthy compromised patients-review of literature.
AB  - Systemic diseases are of major importance in terms of prosthetic restorations
      supported by dental implants in healthy compromised patients. Each treatment
      stage from conception of the treatment plan to the long-term monitoring is under
      the necessity of the interdisciplinary approach to the underlying disease.

PMID- 25870665
TI  - OCT parameters in patients with diabetic maculopathy.
AB  - The treatment of the clinically significant macular edema in patients with
      diabetic maculopathy by the intravitreal administration of corticosteroids and
      antiangiogenic factors requires rapid and more accurate investigation methods
      aimed at following up the dynamic evolution of the structural parameters of the
      retina. The purpose of the study is to compare the outcome of OCT parameters for
      each group (Group A treated by intravitreal administered triamcinolone acetonide
      and Group B treated by intravitreal administered triamcinolone acetonide in
      combination with bevacizumab). Methods involved the selection of cases, dynamic
      measurements of the retina structures, so that, at the end, the data from the two
      groups of patients could be compared. The results showed a positive development
      in the short and medium term in both groups of patients.

PMID- 25870666
TI  - Biological therapies in moderate and severe psoriasis: perspectives and
      certainties.
AB  - An inflammatory, proliferative condition with chronic evolution and systemic
      response, psoriasis, is positioned today among the most common inflammatory skin
      diseases affecting the Caucasian population worldwide. With a significant
      incidence, psoriasis has been increasingly defined as a disease with a major
      impact on the patient's life and the society to which he/she belongs. This paper
      conducts an analysis of the currently available therapies for the treatment of
      moderate and severe psoriasis, therapies with biological agents obtained through
      sophisticated genetic engineering technologies. Recent research and the
      increasing interest in therapeutic methods as complete and efficient as possible
      make us optimistic and confident in the future. 

PMID- 25870668
TI  - Bell's palsy: data from a study of 70 cases.
AB  - Bell's palsy is a condition that affects the facial nerve, which is one of the
      twelve cranial nerves. Its main function is to control all the muscles of the
      facial expression. It is a unilateral, acute, partial or complete paralysis of
      the facial nerve. Bell's palsy remains the most common cause of facial nerve
      paralysis, more often encountered in females aged 17 to 30 years, recurrent in
      many cases and with poor associations with other pathologic conditions. In modern
      literature, the suspected etiology could be due to the reactivation of the latent
      herpes viral infections in the geniculate ganglia, and their subsequent migration
      to the facial nerve but, favorable outcome by using vasodilators, neurotrophic
      and corticosteroid therapy was recorded. 

PMID- 25870667
TI  - Calculus detection technologies: where do we stand now?
AB  - Epidemiological studies have implicated dental calculus as an ideal substrate for
      subgingival microbial colonization. Therefore, the main objective of periodontal
      therapy is to eliminate the microbial biofilm along with the calculus deposits
      from the root surface by root surface debridement. Over the past years, a large
      number of clinical and laboratory studies have been conducted to evaluate the
      efficacy of calculus removal by various methods. None of these conventional
      methods or devices was effective in completely eliminating all the calculus from
      the diseased root surfaces. In this context, a number of newer technologies have
      been developed to identify and selectively remove the dental calculus. Regarding
      this fact, the present article highlights a critical review of these devices
      based on published clinical and experimental data. 

PMID- 25870669
TI  - Factors predicts skin ulcer following coronary artery bypass.
AB  - The number of off-pump coronary artery surgery procedures in high-risk patients
      such as renal failure, hepatic failure and in anticoagulant drug using patients
      is increasing. The associated co morbidity and repeated use of electrocautery in
      postoperative bleeding, caused a susceptibility of patients to pressure or
      electrocautery ulcers. During a period of three years, 1400 off-pump coronary
      artery bypass surgery were performed in our center. Of these patients, 20 (A
      group) suffered from electrocautery sore (ES) and 40 (B group) had pressure sore
      (PS). These patients were compared with respect to variables such as age,
      hypertension, hypercholesterolemia, operating time, smoking, opium using,
      diabetes, weight, sex, respiratory failure, renal failure, and cerebrovascular
      accident, intra aortic balloon pump using, inotropic drug using by x2 or t test,
      according to categorical or continuous variables consequently. Electrocautery
      sore and pressure ulcer as dependence variables and others variables with p value
      less than 0.1 entered a multivariable logistic regression model and odd ratio of
      significant variables were obtained. These two groups of patients were different
      with respect to variables such as age, sex, respiratory failure and
      cerebrovascular accident and, in the logistic regression model, two factors
      predicted pressure sore, respiratory failure and cerebrovascular accident, but
      the only factor that was significant in predicting electrocautery sore in
      multiple logistic regression analysis was postoperative bleeding. Results of this
      study revealed that pressure sore is a patient dependent complication in contrast
      with the electrocautery sore, which is related to technical or device faults and
      to experience and care of operating room staff.

PMID- 25870670
TI  - Perioperatory pain in oncological patient - physiopathological and therapeutical
      implications.
AB  - Perioperatory pain in oncological patients represents a witness of anesthetic
      surgical aggression, frequently exacerbated by the complementary radio
      chemotherapy and also a predictive factor for postoperatory evolution. The
      objectivation of perioperative pain by scales of clinical evaluation does not
      offer a certain and objective quantification; so, the dosing of some hormonal and
      acute phase inflammation mediators could realize a more realistic projection.
      Clinical and biological correlation can offer a support for an adequate and well
      balanced treatment.

PMID- 25870671
TI  - Molecular mechanisms in the pathogenesis of sepsis.
AB  - Innate immune system is a universal form of host defense against infections. The
      recognition of the innate immunity is based on a limited number of encoded
      receptors that have evolved to recognize microbial metabolism products. The
      recognition of these molecular structures allows the immune system to distinguish
      its own infectious components from non-communicable structures. The immune
      suppression is a hallmark of sepsis. The complement system is activated in the
      early stages of sepsis, generating large amounts of anaphylatoxin C5a. Complement
      and TLRs (toll-like receptors) family are two major upstream sensors and
      effectors systems of innate immunity. It was found that TLR4 and complement
      system are involved in the initiation of the inflammatory response in sepsis.
      Clinical studies in which TLR4 was blocked have not shown beneficial effects.
      TLRs, that are a subfamily of PRRs (pattern recognition receptors), have emerged
      as the crucial receptors for the recognition of DAMPs (Damage-associated
      molecular pattern molecules). Recently, a special form of non-coding genetic
      material called microRNA has been highlighted in the complex cascade of sepsis.
      The individual role of every microRNA and the exact role of microRNA network are
      under investigation. Currently, studies are performed in order to find micro RNA
      to be used as biomarkers of sepsis. Researches are performed to determine
      microRNA, small fragments of non-coding RNA, in order to distinguish between
      patients with sepsis and healthy patients, and if the plasma levels of microRNA
      correlate with the severity of the disease. Recent researches report that the
      regulation of gene expression through microRNA plays a very important role in the
      following cellular processes, for example: apoptosis, the differentiation
      process, and the cell cycle. 

PMID- 25870672
TI  - Listeria monocytogenes - characterization of strains isolated from clinical
      severe cases.
AB  - Listeria monocytogenes became an increasing pathogen involved more frequently in
      sporadic severe illnesses and outbreaks of foodborne infections. This study
      investigates in vitro susceptibility of 26 strains of Listeria monocytogenes
      isolated from the clinical specimens collected between March 2009 and November
      2013, from 24 patients hospitalized in three medical institutions in Bucharest.
      All isolates were tested by disk diffusion method to 15 antimicrobial agents, by
      using disk diffusion tests. Among the 26 clinical L. monocytogenes isolates
      tested, no multidrug resistant strains were detected, but 18 (72%) were found to
      be resistant to at least one clinically relevant antibiotic. Among them, 18
      clinical isolates were resistant against ciprofloxacin also. Resistance to
      Ciprofloxacin was particularly noticed to the strains in Romania. Serological and
      molecular typing by Multiplex PCR method detected two molecular types 1/2 a, 3a
      and 1/2 b, 3b, as to the more frequent isolated among studied cases. These types
      of L. monocytogenes could be associated to the higher pathogenic activity of
      immunodeficient patients. 

PMID- 25870673
TI  - Serotonin and the bone assessment.
AB  - INTRODUCTION: Lately, the in vitro and in vivo studies on serotonin metabolism
      have been pointing its influence in bone health. Also, there are no particular
      recommendations in performing the serum serotonin assessment in order to evaluate
      the skeletal status. AIM: We aimed to correlate the bone turnover markers and
      lumbar bone mineral density (BMD) with serotonin. MATERIAL AND METHODS: There is
      a cross-sectional study in Caucasian postmenopausal women. They were not
      diagnosed with carcinoid syndrome, or bone anomalies, and received no treatment
      (including antiresorptives). The following bone formation markers were performed:
      serum alkaline phosphatase (AP), serum osteocalcin (OC), and the bone resorption
      marker: serum CrossLaps (CL). Serum serotonin (high-pressure liquid
      chromatography), as well as central DXA (GE Prodigy) were assessed. RESULTS: 191
      women of 57.1 years mean age were grouped according to DXA (WHO criteria). The
      linear regression analysis between serum serotonin and CL were not statistically
      significant (SS), between serotonin and OC was SS in the newly diagnosed
      osteoporosis group (N=40, r=0.4, p=0.03), between serotonin and AP SS was found
      in osteopenia group (N=88, r=0.24, p=0.03), with no changes when adjusting for
      age and BMI. The partial correlation between serotonin and BMD was not SS.
      DISCUSSION: The study raises the question of serotonin as a bone metabolism
      marker seeing that the results were not consistent. The main limit of our study
      was that we did not analyze the possible use of antidepressants to these women.
      Overall, this was a pilot study in clinical practice where few reports have been
      published, but still necessary, because the use of serum serotonin in current
      skeletal evaluation is still unclear.

PMID- 25870674
TI  - Echinococcal cyst of the left vas deferens - a case report and literature review.
AB  - Cystic echinococcosis or hydatid disease is an important public health issue,
      mainly in developing countries, due to its high prevalence. Echinococcus
      granulosus, a cyclophyllid cestode, the pathogenic parasite found in humans,
      their intermediate host in its way to the final host, the members of canidae
      family. The main sites of infection in humans are the liver and the lungs. There
      have been recorded Rare locations such as the heart, spleen, muscles or
      retroperitoneal have also been recorded. CASE PRESENTATION: We present the case
      of a 29-year-old man, living in rural environment, who was admitted in our Clinic
      for a pelvic cystic tumor and intermittent ureterohydronephrosis. The blood work
      showed positive antibodies for Echinococcus granulosus. An urethrocystoscopy and
      the excision of the tumor were performed. CONCLUSIONS: Although rare, the
      involvement of the male genitourinary tract in cystic echinococcosis is possible
      and can pose important diagnostic challenges.

PMID- 25870675
TI  - The role of immunohistochemical tests in multimodal treatment of the aggressive
      forms of breast cancer.
AB  - Aggressive breast cancer is an invasive form with a differentiation degree G3/G4,
      the absence of estrogen receptor and progesterone and the absence or presence of
      the gene HER 2(+ or 3+). The immunohistochemical tests have an important role in
      establishing the diagnosis and the therapy. MATERIAL AND METHOD: It was shown
      that the aggressive breast cancers, 97 out of 316 cases were operated in the
      period October 2011 - February 2014. The criteria of inclusion/ exclusion in the
      study groups and the treatment schemes were exposed. RESULTS: For the study group
      (group A=43/ group B=45/ group C=9 cases), the distribution according to the age
      group and immunohistochemical classification, were shown and, histologically, the
      type of surgical intervention, postoperative staging, postoperative complications
      were highlighted. CONCLUSIONS: The treatment of the aggressive forms of breast
      cancer, neoadjuvant and adjuvant can both be set only by IHC tests.

PMID- 25870676
TI  - Tattoo-induced psoriasis.
AB  - Koebner phenomenon represents the development of several inflammatory skin
      lesions (psoriasis, lichen planus, vitiligo, etc.) in uninvolved skin following
      various traumatic insults. The case of a 27-year-old male patient with scalp
      psoriasis who was referred to our clinic for generalized psoriatic lesions
      developed two weeks after tattooing his skin at the age of 18 was presented; the
      case illustrated the possibility of Koebner phenomenon induced by skin tattooing
      in patients with psoriasis. 

PMID- 25870677
TI  - Rupture of a splenic artery aneurysm in a previously healthy 53-year-old male.
AB  - Splenic artery aneurysms are unusual clinical conditions that may be ruptured
      resulting into adverse health outcomes. Pregnancy, portal hypertension and
      atherosclerosis are conditions that predispose to the formation of splenic artery
      aneurysms. A rare case of a previously healthy man referred to our department by
      his general practitioner complaining of acute abdominal pain is presented. During
      the hospital stay, the patient presented hemodynamic instability. Abdominal
      computed tomography disclosed perihepatic and perisplenic fluid accumulation. A
      diagnosis of ruptured splenic artery aneurysm was performed and the patient was
      operated successfully with splenectomy and ligation of the splenic artery.
      Although the condition is rare, physicians have to be aware of the high mortality
      rates caused by a ruptured splenic artery aneurysm and include this in the
      differential diagnosis when they encounter patients with acute abdominal pain and
      hemodynamic instability. 

PMID- 25870678
TI  - Visual acuity outcome in patients with diabetic maculopathy.
AB  - The purpose of this study is to follow up visual acuity in patients diagnosed
      with clinically significant macular edema and treated by an intravitreal
      injection of triamcinolone acetonide or in combination with bevacizumab. The
      working method: based on the selectivity criteria we involved 295 patients (460
      eyes), divided into 2 groups according to the treatment administered and one
      control group. The results showed a better preservation of the functional
      parameter for the group of patients treated with intravitreal injection of
      triamcinolone acetonide and bevacizumab.

PMID- 25870679
TI  - Speleotherapy - modern bio-medical perspectives.
AB  - Speleotherapy - a special form of climatotherapy - uses certain conditions
      specific to caves and salt-mines to treat several medical conditions, especially
      respiratory and skin-related. This reduces all types of irritations and therefore
      disease symptoms are mitigated or fully suppressed while the patient is
      accommodated into the salt-mine. OBJECTIVE: Influence of microclimate in salt
      mines of Turda, Dej and Cacica on morphology and electrophoretic expression of in
      vitro lung and skin fibroblasts acquired from the lung and hypodermic tissues of
      Wistar rats, in normal conditions and after ovalbumin-induced asthma,
      respectively after experimental injuries and burns. MATERIALS AND METHODS: skin
      fibroblast cultures acquired from lung and hypodermic tissue sampled from Wistar
      rats. Cultures acquired are developed in fibroblast monolayer attached to the
      culture dish. Wistar rats with weight between 75 -100 g were divided in three
      groups: one control group, one group with experimental asthma, one group with
      injuries and burns. 10 animals from each group were sent to salt-mines in Turda,
      Dej and Cacica for 14 days and kept in a saline environment, similar to
      speleotherapy. RESULTS: Speleotherapy applied to Wistar rats determined
      significant differences in cellular morphology and in electrophoretic expression
      of lung and skin fibroblasts from primary cultures. CONCLUSIONS: Results of this
      survey indicates that speleotherapy induces changes in morphology and protein
      expression of in vitro lung and skin fibroblasts, and these changes support the
      therapeutic effects of speleotherapy.

PMID- 25870680
TI  - Multiresistance to antibiotics of Salmonella enterica serovar Typhimurium strains
      producing extended spectrum beta-lactamases (ESBLs).
AB  - The purpose of the study is to give the rising incidence of Salmonellosis and the
      continuous decrease of sensitivity of Salmonella to a range of antibiotics, the
      prime importance of the choice of optimal anti-infective chemotherapy in order to
      prevent the selection of multidrug-resistant strains (MDR). We have studied 54
      strains of Salmonella sent for further investigation to "Cantacuzino" NIRDMI
      Bucharest. The statistical analysis was based on the interpretation pathogen
      susceptibility and analyzed according to CLSI recommendations 2009, which
      revealed that 8 (14,81%) identified as S. enterica serovar Typhimurium group,
      presented a phenomenon of MDR. S. Typhimurium strains producing ESBL showed
      resistance mechanisms associated with beta-lactam resistance to aminoglycosides,
      quinolones, sulfonamides and tetracyclines. 

PMID- 25870681
TI  - Surveys on therapeutic effects of "halotherapy chamber with artificial salt-mine
      environment" on patients with certain chronic allergenic respiratory pathologies
      and infectious-inflammatory pathologies.
AB  - Halotherapy (HT), derived from speleotherapy in salt mines, is also a drug-free
      therapeutic method. HT effects vary depending on the therapeutic method and the
      structure of halotherapy environment. The purpose of this article is to show the
      HT effects of "halotherapy chamber with artificial salt-mine environment" of the
      National Institute of Rehabilitation, Physical Medicine and Balneoclimatology
      (INRMFB), on patients with bronchial asthma and other chronic, infectious
      inflammatory and allergic respiratory diseases, describing the clinical effects
      on certain nonspecific resistance factors, on markers of inflammatory processes
      and on certain immunological changes. Patients were clinically assessed, with the
      application of hematologic investigations, analysis of nonspecific resistance to
      infection and of inflammatory process markers, immunologic assessments, analysis
      of sodium and potassium concentrations, of mineralocorticoid function and other
      biochemical tests. For the experimental HT therapy performed in the "halotherapy
      chamber with artificial salt-mine environment" of INRMFB, 15 patients suffering
      from bronchial asthma, allergic rhinitis, chronic bronchitis, chronic obstructive
      bronchopneumopathy were selected, based on specific medical indications and
      contraindications and applying ethical principles, as well as 4 patients with
      similar pathologies for the control group, who underwent in-home drug treatment.
      After the specific halotherapy treatment on patients with bronchial asthma,
      chronic bronchitis and chronic obstructive bronchopneumopathy, which also showed
      other chronic, infectious-inflammatory and allergic respiratory pathologies,
      triggering of anti-inflammatory (and also anti allergic) mechanisms and healing
      effects on inflammatory process were noted. Data acquired also proved the halo
      therapeutic effect causing the reduction of sensitiveness of body in patients
      with bronchial asthma.

PMID- 25870682
TI  - Use of amniotic membrane in bullous keratopathy palliative care.
AB  - BACKGROUND: Assessment of efficiency of amniotic membrane covering in the
      improvement of bullous keratopathy symptoms. MATERIAL AND METHOD: The paper
      represents a clinical prospective study, which includes 42 patients diagnosed
      with bullous keratopathy and operated between January 2009 and November 2013 in
      the Department of Clinical Ophthalmology from "Dr. Carol Davila" Central Military
      Emergency Hospital. Follow up between 6 and 48 months, with an average of 22
      months. Subject to research: corneal re-epithelisation, epithelial bullae, pain
      and photophobia relapse. RESULTS: In 37 cases, the symptoms improved, in 8 cases
      the minimum symptoms persisted and in 29 cases the symptoms completely
      disappeared. In 5 cases, there were no significant improvements, symptoms
      reappeared briefly after membrane resorption. CONCLUSIONS: Amniotic membrane
      covering represents an efficient palliative care means in oedematous keratopathy.

PMID- 25870683
TI  - Some considerations concerning cochlear implantation in IFACF-ORL.
AB  - The article analyzes the patients who have received a cochlear implant at "Prof.
      Dr. Dorin Hociota" Institute of Phonoaudiology and Functional ENT Surgery,
      Bucharest, over a period of 13 years, from the beginning of this program in the
      year 2000. It presents the types of devices used, the particularities of the
      patients, the surgical techniques and the outcome, critically analyzing the
      complications encountered. The authors' comments on the selection of patient
      protocol, surgical intraoperative challenges and cochlear implant technologies
      and capabilities are presented. 

PMID- 25870684
TI  - Initiation, evolution, excellency and the "sacred rigor of surgery".

PMID- 25870685
TI  - Good nutrition practice.

PMID- 25870686
TI  - Scores and scales used in emergency medicine. Practicability in toxicology.
AB  - Medical scores, criteria and classification systems support clinical decision
      making and management. They enable the clinician to predict the outcome, stratify
      risk, assess conditions and diagnose diseases accurately. In the emergency
      medicine, it is very important to ascertain safety criteria to discharge
      patients, time to remain in the E.R., and also ascertain the time intervals for
      discharge/admission. The use of the scores in the emergency medicine, toxicology
      and other areas of intensive medicine have become increasingly efficient.
      Creating a prognostic score for the acute intoxications to be used by the
      personnel from the Emergency Departments may have positive effects in the
      management of the poisoned patients (e.g. the admission in a certain treatment
      space: cases expected to have a trend towards worsening will be directed to the
      resuscitation space and after a short period of time admitted in the appropriate
      facility; this way, the bed occupancy time in the Emergency Department will be
      shortened). 

PMID- 25870687
TI  - Encapsulating Peritoneal Sclerosis - A rare and serious complication of
      peritoneal dialysis: Case series.
AB  - INTRODUCTION: Encapsulating peritoneal sclerosis is a pathological entity mainly
      associated with peritoneal dialysis (PD). The clinical syndrome is characterized
      by various degrees of intestinal obstruction due to thickening, sclerosis and
      calcification of peritoneum resulting in the encapsulation and cocooning of the
      bowel. It is a rare but potentially devastating complication associated with a
      considerable morbidity and mortality. MATERIALS AND METHODS: Cases of
      encapsulating peritoneal sclerosis (EPS), diagnosed in the Surgical Clinic of
      "Cantacuzino" Hospital, between 2007 and 2014 were retrospectively reviewed.
      During this interval, 432 surgical interventions related to peritoneal dialysis
      were performed: 306 peritoneal access interventions and 124 complications, of
      which 15 patients with EPS. RESULTS: In all but two cases, the EPS diagnostic was
      established at the time of the surgical intervention addressed to other
      complication or pathology. Moreover, in 2 of the 15 patients the diagnostic was
      established approximately 5 months after PD was discontinued, and, in one of
      these patients at the time of the extraction of the dialysis catheter. 12 of 15
      patients were diabetic. Most patients had a history of multiple peritonitis
      episodes. All the patients required the passing from peritoneal dialysis to
      hemodialysis. There were 4 deaths (26,6%) of which one was around two months from
      the diagnosis. CONCLUSIONS: The timely diagnosis of the condition and the
      appropriate phase-specific treatment is of utmost importance in EPS. In advanced
      stages, the surgical intervention performed by a well-trained team could achieve
      good long-term results.

PMID- 25870688
TI  - The new prognostic-therapeutic index - an easy method of establishing surgical
      indication in the pathology of the diabetic foot.
AB  - HYPOTHESIS AND AIM: The large number of invalidating surgical interventions in
      patients suffering from lesions of the diabetic foot, the late recognition of the
      lesions and sometimes the wrongful interpretation of their severity, have made
      necessary a multi-parameter study of these types of patients and the elaboration
      of a therapeutic-prognostic index to guide the physician in adopting the adequate
      method of treatment. Starting with the therapeutic-prognostic index imagined by
      professor Traian Patrascu, we have elaborated a new therapeutic prognostic index,
      by adding new, statistically significant parameters, for the purpose of
      facilitating the surgical indication, depending on the lesion type. METHODS: A
      number of 929 patients who were admitted at the Surgery Clinic of the "Dr. I.
      Cantacuzino" Hospital, between January 2013 and June 2014, have been analyzed, of
      whom 450 were evaluated retrospectively and 479 prospectively. RESULTS: The new
      therapeutic prognostic index has been calculated for the retrospective lot,
      resulting into a concordance between the actual surgical intervention and the
      prognostic index of 79.4% and, for the patients evaluated prospectively, we have
      found a confirmation of the relation of 82.6% between the performed surgical
      intervention and the forecasted surgical intervention, by calculating the index.
      DISCUSSION: The new therapeutic-prognostic index represents an easy method of
      establishing the therapeutic conduct of the patient suffering from lesions of the
      diabetic foot. It is of major use in preventing the execution of such surgical
      interventions that may be disproportionate compared to the severity of the
      lesions, especially in facilities where the pathology of the diabetic foot is
      less known.

PMID- 25870689
TI  - The concept of marketing in the public-private partnership in the medical system
      in Romania.
AB  - During the transition period, the Romanian medical system, subject (like other
      areas) to a process of reform, had to go through a difficult path, not without
      obstacles (malpractice, underfunding, embezzlement scandals in the media etc.).
      Consequently, Romania has faced (and unfortunately still is still facing) the
      massive exodus of health professionals to countries where they can benefit from
      better working conditions and payment, and those who suffer from health care
      crisis are the patients. Reform means "the people in the system for the people",
      which requires a change of mindset within the medical staff, especially in the
      continuous professional development. However, to talk about the quality of the
      medical act requires that all those involved in the medical system should create
      appropriate conditions - i.e. advanced technical equipment and appropriate
      salaries. In addition, as underfunding is the main cause of failure in the health
      system, that management remains the only tool that can lead to the appropriate
      use of the existing resources and the quality of health services. Therefore, the
      idea of public-private partnership - which occurred as a challenge, especially
      after the EU accession - can be considered a solution designed to improve the
      quality and cost of health services. In other words, the cooperation of the
      private sector with the public authority means increasing the rigor of the
      medical equipment performance, fostering professional competition, and an
      increased attention to the patient, in a word: performance. Currently, more and
      more frequently, the management has studied to identify opportunities for
      innovation in health care services in an attempt to bring together patients and
      practitioners in the field by resorting to the identification of the ways they
      can receive health care services promptly, fairly and efficiently. Therefore, a
      clear and responsible design in the spirit of ethics and medical ethic will help
      the marketing manager solve many of the complex issues raised by the marketing
      activity in the field of health care. 

PMID- 25870691
TI  - Prognostic intraoperative factors in severe acute pancreatitis.
AB  - Acute pancreatitis is a serious disease. Triggered by the local inflammation of
      the pancreas, it can cause inflammation in various organs and systems in the
      body. It is important to identify severe forms of acute pancreatitis with an
      increased morbidity and mortality rate. Lately, internationally, numerous
      clinical and paraclinical factors predicting the severity of acute pancreatitis
      have been proposed. The purpose of the study is to identify the prognostic
      intraoperative factors of severity. The prospective study was conducted over a
      period of four years, between 2007 and 2010 and included 238 patients treated in
      a surgical clinic in Bucharest. 103 patients experienced a severe form of acute
      pancreatitis, which means 67.95% of all operations practiced. We monitored
      intraoperative factors, in particular: the presence and/ or the extent of
      pancreatic necrosis, common bile duct lithiasis and intraperitoneal fluid,
      parameters proposed to become statistically prognostic factors in the development
      and long-term morbidity of acute pancreatitis. The presence and/ or extension of
      necrosis was identified in the histopathology only in patients with severe acute
      pancreatitis. 71.43% of the patients with common bile duct lithiasis and 73.91%
      of the patients with inflammatory intraperitoneal fluid had severe acute
      pancreatitis. Most patients who developed postoperative complications (86.49%) or
      who required a surgical intervention (85.71%), presented a severe form of the
      disease. CONCLUSIONS: pancreatic necrosis, common bile duct lithiasis and
      intraperitoneal fluid may contribute to a more precise prediction of severity, as
      confirmed by international literature.

PMID- 25870690
TI  - Barrett esophagus: history, definition and etiopathogeny.
AB  - The injury of the esophageal epithelium may be determined by the reflux of the
      gastric acid in the esophagus. Barrett's esophagus (BE) is characterized by the
      replacement of the normal squamous epithelium with the columnar epithelium, when
      the healing of the lesion occurs. According to some studies, the incidence of the
      esophageal adenocarcinoma in patients with BE is of about 0,5% per year. The term
      Barrett's esophagus is subjected to interpretation nowadays, so it lacks the
      clarity needed for the clinical and scientific communication on the subject of
      columnar metaplasia of the esophageal mucosa. The major pathogenetic factor in
      the development of BE is represented by the reflux disease. The cellular origin
      of BE is controversial and it represents an issue that needs to be resolved
      because it will have implications in the putative molecular mechanisms underlying
      the metaplastic process. The epigenetic or genetic changes, which alter protein
      expression, function, and/ or activity, in post-mitotic cells to drive
      transdifferentiation or in stem/ progenitor cells such that they are reprogrammed
      to differentiate into columnar rather than squamous cells, are driven by the
      inflammatory environment created by chronic reflux. In order to be able to
      develop better therapeutic strategies for the patients with this disease, an
      increasing interest in understanding the pathogenesis of BE at the cellular and
      molecular level presents these days. 

PMID- 25870692
TI  - Clinical significance of HPV-DNA testing for precancerous cervical lesions.
AB  - Cervical screening by using cytology was proven efficient in reducing the
      mortality secondary to cervical cancer, but this method has limitations. High
      risk HPV infection is essential for cervical cancer development so HPV testing is
      a new tool used for screening patients for cervical neoplasia. HPV testing was
      proven most useful for women over 30 years old, in cases in which cytology
      identified ASC-US and after treatment for CIN. This article outlines the clinical
      significance of HPV-DNA testing for precancerous cervical lesions and the
      evidence that stands behind these recommendations.

PMID- 25870693
TI  - Involvement of vasoactive substances in hemodynamics disturbances in cirrhosis.
AB  - Cirrhosis is a pathological entity characterized by the association of hepatocyte
      necrosis, fibrosis and regenerative nodules; hemodynamic and neurohormonal
      metabolic factors intervening in its development mechanisms, resulting in hepatic
      stellate cell activation and transformation and development of liver fibrosis.
      Cytokines are key modulators of liver cell fibroblast transformation.
      Prostaglandins play an important role in the control of vascular tone and in
      thrombosis; Angiotensin II stimulates fibroblast proliferation by AT-1 receptors.
      Thrombin influences cellular remodeling in the liver and cardiovascular cirrhotic
      patients. Oxidative stress is involved in the development of liver cirrhosis by
      primary and secondary biological irreversible effects. Complex etiology involving
      vasoactive substances, oxidative stress in the pathogenesis of liver cirrhosis,
      require further studies to elucidate the mechanisms involved in hemodynamic
      disturbances associated with this disorder. 

PMID- 25870694
TI  - Chromosomal translocations highlighted in Primitive Neuroectodermal Tumors (PNET)
      and Ewing sarcoma.
AB  - Almost 200 molecular markers in oncology, very important in the diagnosis,
      prognostic and treatment were identified. The cell and tissue markers and also
      the circulating (sanguine) ones are genetic markers of the hereditary and non
      hereditary tumors. Also extremely important are the regulatory ways of cell
      growth and differentiation, of the cell "senescence" and cell death (apoptosis).
      The term of "tumor marker" concerns a variety of molecules or processes that are
      different in the normal cell compared with the malign cell. The tumor markers may
      include modifications to the genetic level (mutations, deletions or genes
      amplifications) to the transcription level (super expression or sub-expression),
      to the translation level (high or low quantities of proteins, abnormal
      glycosylation of proteins) and/or to the functional level (the level of cell
      differentiation or presence of neo-vascularisation). Cancer is a genetic disease.
      There is a deregulation at the genes level that controls the cell division and
      withdrawal from the cell cycle or there is a genetic susceptibility. In other
      words, cancer is an end point for several phases in which the oncogenes and
      stimulatory signals and inhibitors produced and controlled by the products of
      these oncogenes are involved. 

PMID- 25870695
TI  - Neonatal hypoglycemia screening in newborns from diabetic mothers--arguments and
      controversies.
AB  - The most important known metabolic complication of the newborns from diabetic
      mothers, including diabetes type 1 and 2 and gestational diabetes, is the
      postnatal hypoglycemia. If unrecognized and undiagnosed, hypoglycemia in this
      particular high-risk group can determine severe neurological lesions and even
      death, in a significantly higher proportion than those from the general
      population. The present paper brings arguments for the crucial importance of
      screening for post-natal hypoglycemia in the early hours after birth, and
      discusses the management strategies and the topics that still remain in debate. 

PMID- 25870696
TI  - Cirrhotic cardiomyopathy.
AB  - Cardiomyopathy is a chronic disease of the myocardium characterized by an
      abnormal dilatation and thinning of the left ventricular (LV), associated with
      the contractile dysfunction of the muscle and loss of pump capacity, resulting in
      the occurrence of arrhythmias and myocardial infarction. It has many causes and
      can occur in the liver pathology inclusively. 

PMID- 25870697
TI  - Thymus vulgaris essential oil: chemical composition and antimicrobial activity.
AB  - The study was designed to determine the chemical composition and antimicrobial
      properties of the essential oil of Thymus vulgaris cultivated in Romania. The
      essential oil was isolated in a yield of 1.25% by steam distillation from the
      aerial part of the plant and subsequently analyzed by GC-MS. The major components
      were p-cymene (8.41%), gamma-terpinene (30.90%) and thymol (47.59%). Its
      antimicrobial activity was evaluated on 7 common food-related bacteria and fungus
      by using the disk diffusion method. The results demonstrate that the Thymus
      vulgaris essential oil tested possesses strong antimicrobial properties, and may
      in the future represent a new source of natural antiseptics with applications in
      the pharmaceutical and food industry. 

PMID- 25870698
TI  - Surveillance in Barrett esophagus.
AB  - The only known precursor of the esophageal adenocarcinoma (EAC) is represented by
      the Barrett's esophagus (BE). EAC incidence has increased sharply in the last 4
      decades. The annual conversion rate of BE to cancer is small but significant;
      therefore the identification of patients at a higher risk of cancer represents a
      dilemma. The endoscopic surveillance of BE aims to detect dysplasia and in
      particular high-grade dysplasia and intramucosal cancers that can be
      endoscopically treated before progressing to invasive cancer with lymph node
      metastases. Using standard white light endoscopy (WLE), these high-risk lesions
      are often subtle and hard to detect. In addition to high-definition standard
      endoscopy, chromoendoscopy (CE), virtual chromoendoscopy (e.g. narrow band
      imaging), and confocal laser endomicroscopy might increase the diagnostic
      efficiency for the detection of dysplastic lesions and can also increase the
      diagnostic efficiency for the detection of BE dysplasia or cancer. This ability
      to detect subtle mucosal abnormalities that harbor high-grade dysplasia (HGD) or
      intramucosal carcinoma might enable endoscopists skilled in the assessment of BE
      to perform targeted rather than random biopsies. The standard protocol will
      remain the careful examination by using conventional high-resolution endoscopes,
      combined with a longer inspection time, which is associated with an increased
      detection of dysplasia until these modalities have been demonstrated to enhance
      efficiency or be cost effective. Many of the limitations of the current clinical
      standard may be overcome in the future by the use of multi-modal imaging combined
      with molecular information. 

PMID- 25870699
TI  - Recurrences of Bell's palsy.
AB  - INTRODUCTION: Bell's palsy in known as the most common cause of facial paralysis,
      determined by the acute onset of lower motor neuron weakness of the facial nerve
      with no detectable cause. With a lifetime risk of 1 in 60 and an annual incidence
      of 11-40/100,000 population, the condition resolves completely in around 71% of
      the untreated cases. Clinical trials performed for Bell's palsy have reported
      some recurrences, ipsilateral or contralateral to the side affected in the
      primary episode of facial palsy. Only few data are found in the literature.
      Melkersson-Rosenthal is a rare neuromucocutaneous syndrome characterized by
      recurrent facial paralysis, fissured tongue (lingua plicata), orofacial edema.
      PURPOSE: We attempted to analyze some clinical and epidemiologic aspects of
      recurrent idiopathic palsy, and to develop relevant correlations between the
      existing data in literature and those obtained in this study. METHODS &
      MATERIALS: This is a retrospective study carried out on a 10-years period for
      adults and a five-year period for children. RESULTS: A number of 185 patients
      aged between 4 and 70 years old were analyzed. 136 of them were adults and 49
      were children. 22 of 185 patients with Bell's palsy (12%) had a recurrent partial
      or complete facial paralysis with one to six episodes of palsy. From this group
      of 22 cases, 5 patients were diagnosed with Melkersson-Rosenthal syndrome. The
      patients' age was between 4 and 70 years old, with a medium age of 27,6 years. In
      the group studied, fifteen patients, meaning 68%, were women and seven were men.
      The majority of patients in our group with more than two facial palsy episodes
      had at least one episode on the contralateral side. CONCLUSIONS: Our study found
      a significant incidence of recurrences of idiopathic facial palsy. Recurrent
      idiopathic facial palsy and Melkersson-Rosenthal syndrome is diagnosed more often
      in young females. Recurrence is more likely to occur in the first two years from
      the onset, which leads to the conclusion that we should have a follow up of
      patients diagnosed with Bell's palsy for at least two years from the onset,
      especially in children' case. The frequency of recurrent facial palsy in children
      was similar to that in adults. Recurrent idiopathic facial palsy is not known
      enough and needs further controlled studies.

PMID- 25870700
TI  - HPV-DNA testing for patients with ASC-US helps identify the women who have a high
      risk for precancerous cervical lesions.
AB  - BACKGROUND: The cytological interpretation of ASC-US represents a category of
      morphologic uncertainty. For patients with this result, other tests are necessary
      in order to determine the risk for cervical lesions. MATERIALS AND METHODS: 198
      patients with ASC-US cytology have been analyzed between 2008 and 2013. All the
      patients included in the study have subsequently had a high oncogenic HPV testing
      and colposcopy risk. 103 (52%) patients tested positive for high risk HPV and 21
      (10%) had associated colposcopy changes and precancerous and cancerous lesions
      identified through biopsy. 95 (48%) patients tested negative for HPV and none of
      these women had lesions at colposcopy. RESULTS AND DISCUSSION: High oncogenic
      risk HPV testing was proven useful in identifying the patients with ASC-US
      cytology who are at high risk for cervical lesions (100% sensibility). In this
      study, the HPV testing had a negative predictive value of 100%, which uselessly
      renders a further colposcopy evaluation. HPV testing for women with ASC-US is not
      specific in identifying women with cervical lesions (Specificity 53%) and this
      results from a high prevalence of limited HPV infections in an age group which is
      less than 30 years old. CONCLUSIONS: High risk HPV testing for women with ASC-US
      cervical cytology is useful in determining the risk for precancerous and
      cancerous cervical lesions. A positive result is associated with a high risk for
      cervical lesions (20%) and for these patients colposcopy is necessary. For women
      with a negative result, the risk for cervical lesions is practically null so
      colposcopy is not required.

PMID- 25870701
TI  - Outcome of patients in acute poisoning with ethylene glycol--factors which may
      have influence on evolution.
AB  - INTRODUCTION: Intoxication with ethylene glycol occurs as a result of intentional
      ingestion in suicide attempts or accidentally. Clinical ethylene glycol poisoning
      is not specific and occurs in many poisoning cases therefore the diagnosis is
      difficult. Early diagnostic and establishment of therapy are very important for a
      favorable evolution. The mortality rate of ethylene glycol intoxication ranges
      between 1 and 22% depending on the amount of alcohol ingestion and the time
      period between alcohol ingestion and initiation of therapy. METHODS:
      Retrospectively analyzed data from 18 patients admitted with ethylene glycol
      poisoning in the emergency department between 2011 and 2012. The following were
      taken into consideration: incidence of intoxication in the group study, medical
      history, the amount ingested and the time since the ingestion of ethylene glycol
      and the admission to hospital, presence of metabolic acidosis and laboratory test
      results on admission (urea, creatinine osmolar or anion gaps), the treatment
      initiated and the outcome of the patient. RESULTS: 18 patients with ethylene
      glycol intoxication were admitted to hospital between 2011 and 2012. The initial
      diagnosis based on a detailed clinical history in combination with the presence
      of metabolic acidosis with elevation of the osmolar or anion gaps. 12 of the 18
      patients were man (66%) and age range interval was between 23 and 77 years. The
      time from the ingestion of ethylene glycol and the admission to hospital was
      between 30 minutes and older than 24 hours. 14 patients have been presented
      earlier to the hospital, between 30 minutes and 12 hours (in the first part of
      the clinical stage) and 13 of the 14 patients had a favorable evolution. One of
      these patients had an unfavorable evolution. Regarding this patient, the amount
      ingested was unknown. 10 of the 18 patients had a voluntary ingestion (55,55%)
      and 6 of the 18 patients had an alcoholism medical history. The amount ingested
      by the patients was between 20 ml and 500 ml. Metabolic acidosis was present up
      to 55,55% (10 of the 18 patients) in the blood gas analysis on admission, with pH
      on admission between 6.9 and 7.27, with anion gap ranging between 16.3 mmol/l and
      32.6 mmol/l (normal range 8-16 mmol/l). Ten patients also had an increased level
      of urea and creatinine with a level between 1.24 to 6.85 mg/dl for creatinine
      (normal range 0.5-1.2 mg/dl) and 49 to 98 mg/dl for urea (normal range 15-43
      mg/dl) and developed acute kidney injury that required regular HD sessions.
      Mechanical ventilation was required for 7 of the 18 patients (38.88%). Five
      patients died (27.77%). Although metabolic acidosis was corrected under
      hemodialysis, there were patients who had multiple organ failure and systems:
      acute respiratory failure requiring ventilator support, acute renal failure
      requiring dialysis daily sessions, altered state of consciousness. CONCLUSIONS:
      The early diagnostic and exclusion of the other diseases and other poisoning led
      to a specific treatment of the intoxication. The time from the ingestion of
      ethylene glycol and the early establishment of therapy is very important for a
      favorable evolution and can prevent substantial mortality.

PMID- 25870702
TI  - Colocalization methods in pituitary tumorigenesis aged-related in MEN1 KO and
      wild type mice.
AB  - BACKGROUND: Colocalization analysis of confocal fluorescence and electron
      microscopy (EM) are important tools to detect the expression of multiple anterior
      pituitary hormones within the same cell. Heterozygous (Men1+/-) mice developed
      pituitary tumors, mostly reported somatolactotrophinomas and ACTH secreting
      pituitary adenomas but also nonfunctioning tumors. The aim of the study was to
      run immunohistochemistry protocols to study colocalization of pituitary hormones
      in newborn mice in tumoral and non-tumoral tissue in MEN1-KO and wild type
      control mice. METHODS: Pituitary samples from nine Men1+/- mice, 29-34 days old
      male mice (n=8) and one year old (n=1) and control group, four new born (1,5 days
      old) wild type (mus musculus) mice were analyzed by immunofluorescence
      immunohistochemistry (GH, PRL, gonadotrophs) to find hormonal colocalization in
      pituitary cell. Moreover, pituitaries were embedded in LRGold for immunogold
      labeling technique (GH, PRL, gonadotrophs and alpha-SU) also. RESULTS: Pituitary
      tumors, immunoreactive only for PRL were found in three MEN1 - KO mice. No sign
      of pituitary hyperplasia was found in MEN1-KO. MEN1-KO non-tumoral pituitary
      displayed similar immunoreactivity to wild type pituitary. Colocalization studies
      revealed individual cells PRL-FSH immunoreactive and GH-FSH immunoreactive in the
      non-tumoral tissue from MEN1-KO mice and in wild type pituitaries respectively
      but no colocalization in the tumoral tissue. In conclusion, colocalization is a
      feature of neonate mouse pituitary but not in adults. The MEN1-KO pituitary
      tumors were prolactinomas and unlike non-tumoral pituitary tissue of MEN1-KO,
      displayed no PRL-FSH colocalization.

PMID- 25870703
TI  - Assessment of acid-base balance at birth in newborns from diabetic mothers.
AB  - Newborns from diabetic mothers are more frequently born prematurely, large for
      the gestational age, with difficult respiratory adaptation and risk of RDS
      (respiratory distress syndrome) and, subsequently, exposed to a higher risk of
      perinatal distress, hypoxia, metabolic stress and hematologic alterations.
      Comparing the status at birth of 120 newborns from mothers with diabetes, with
      120 controls from uncomplicated pregnancies, over a period of 4 years, in a
      specialized tertiary center, no significant differences in the immediate outcome
      of such newborns and similar incidence of hypoxia at birth were shown, as
      illustrated by the parameters of the acid-base balance (cord pH, BE and HCO3).
      However, there are significant differences in the route of delivery, with a
      predominance of C-section deliveries in the diabetic group (4 out of every 5
      cases), which might be an important contribution to the relative good status of
      these newborns at birth. Although balanced at birth, the newborns from diabetic
      mothers need intensive monitoring and care in the subsequent hours after birth,
      for important risks such as hypoglycemic episodes. 

PMID- 25870704
TI  - The role of computed tomography in the diagnosis and treatment of calcaneal
      fractures.
AB  - The intra articular fractures represent a challenge for the orthopaedic surgeons.
      Because of the three-articulary surfaces, the calcaneus represents a permanent
      subject of discussion about the investigation and treatment opportunities. In a
      retrospective audit of patients hospitalized in our clinic, I tried to identify
      the opportunity of the CT scan as a preoperative investigation protocol in
      calcaneal fractures, the results showing that the CT scan represents a mandatory
      standard in calcaneal fractures. 

PMID- 25870705
TI  - Diagnosis characteristics and therapeutical options of infectious complications
      associated with peritoneal dialysis.
AB  - INTRODUCTION: The infectious syndrome associated with peritoneal dialysis is the
      most important complication of this substitution method of the renal function,
      also being the main cause of method failure. Refractory peritonitis can cause
      real problems in the differential diagnosis with secondary peritonitis, which can
      delay the surgical intervention and endanger the patient's life. MATERIALS AND
      METHODS: The patients with an end stage renal disease under peritoneal dialysis,
      who were admitted to "I. Juvara" Surgical Clinic of "Dr. I. Cantacuzino" Clinical
      Hospital, between 2007 and 2011, were retrospectively analyzed for catheter
      removal/ replacement due to infectious complications or ultrafiltration failure.
      RESULTS: 55 patients were identified: 33 with infectious complications (exit
      site, tunnel infections 4 and peritonitis 29) and 22 with loss of peritoneum
      ultrafiltration capacity. The patients with ultrafiltration failure had a longer
      duration of PD and a smaller number of peritonitic episodes (0.28 episodes/ year
      at risk in the ultrafiltration failure group vs. 0.98, in the group of infectious
      complications). The removal of the catheter was the only surgical procedure
      performed for the patients with ultrafiltration failure, while the patients with
      peritonitis needed additional gestures like an exploratory laparotomy with
      peritoneal lavage and drainage and adhesiolysis in the majority of cases. In the
      group with infectious complications, 4 patients died: 2 by multisystem organ
      failure due to prolonged sepsis, one developed an upper gastrointestinal bleeding
      followed by respiratory insufficiency and one had in cataclysmic gastrointestinal
      bleeding which rapidly led to death. CONCLUSIONS: The immediate operative
      approach for an infectious peritoneal syndrome under peritoneal dialysis is
      seldom necessary. The surgical observation is absolutely mandatory in every case.
      The absence of a response to the proper medical treatment is an indication of
      peritoneal cavity exploration including laparoscopy/ laparotomy. Any delay in the
      diagnosis and definitive treatment gives an extremely high mortality rate.

PMID- 25870706
TI  - Mean platelet volume variability in young patients with non-ST elevation acute
      myocardial infarction.
AB  - INTRODUCTION: Platelet activation plays an important role in the pathophysiology
      of non-ST elevation acute coronary syndromes (ACS). Mean platelet volume (MPV),
      an indicator of platelet reactivity, was previously associated with an increased
      risk of acute coronary events. OBJECTIVE: To investigate the MPV variability in
      young patients presenting with NSTEMI, as compared to young patients with
      cardiovascular risk factors and no overt ischemic cardiac disease, as well as
      with elderly patients presenting with NSTEMI. METHODS: We analyzed data from 174
      patients admitted in our cardiology department between January 2009 and December
      2010: 35 patients younger than 45 years of age with NSTEMI, 41 patients younger
      than 45 without ACS and 98 patients older than 45 with NSTEMI. RESULTS: Young
      patients with NSTEMI had a significantly higher mean MPV (8.88 +/- 1.14fl) than
      young patients without ACS (8.31 +/- 0.37fl, p<0.01), while the older subjects
      with NSTEMI had the highest mean MPV (9.48 +/- 1.35fl, p=0.02). MPV correlated
      with age (r=0.375, p<0.0001). After a multivariate analysis, elevated levels of
      MPV were independent predictors of NSTEMI in young patients (odds ratio [OR]
      2.75, 95% CI 1.04-7.92, p=0.04), while hypertension (OR 0.34, 95% CI 0.6-1.78,
      p=0.20), dyslipidemia (OR 1.61, 95% CI 0.17-14.51, p=0.67), obesity (OR 5.77, 95%
      CI 0.80-41.53, p=0.08) and smoking status (OR 8.97, 95% CI 0.84-95.26, p=0.06)
      were not. CONCLUSION: NSTEMI is associated with high MPV in old as well as in
      young patients. Elevated MPV is predictive for NSTEMI in young patients,
      separately of a high cardiovascular risk profile.

PMID- 25870707
TI  - Detection of EWS/FLI-1 fusion in non-Ewing soft tissue tumors.
AB  - OBJECTIVES: EWS/FLI-1 fusion mainly appears in Ewing's sarcoma or the primitive
      neuroectodermal tumors and represents a genomic marker for these tumors. However,
      it can appear with lower frequency in other soft tissue tumors. The paper
      investigates the presence of EWS/FLI-1 fusion in clinically diagnosed sarcoma
      belonging to different non-Ewing connective tissue tumors in order to search for
      a possible new biomarker valuable for investigators. METHODOLOGY: 20 patients
      with soft tissue tumors, who underwent surgery, were tested. Intra-operative
      samples of normal and tumor tissue were collected for histopathological diagnosis
      and genetics determinations. The patients' RNA from tumor and normal peritumoral
      tissue was extracted and EWS/FLI-1 fusion screened by quantitative real-time PCR.
      The relative expression of the fusion in the tumor sample was compared to the
      similar expression in normal tissue. RESULTS: The amplification in the threshold
      zone was shown by 5 samples (25%): 2 clear cell sarcoma, 1 fibrosarcoma, 1
      malignant tumor of nerve sheath, 1 metastatic adenocarcinoma. We differentiated
      between the unspecific amplification and concluded that these are weak positive
      results. CONCLUSIONS: Genomic investigation may establish the tumor malignancy
      and its possible affiliation earlier than histopathology. It can support the
      screening of EWS/FLI-1 fusion in a larger variety of clinically diagnosed soft
      tissue tumors.

PMID- 25870708
TI  - The relevance of the psychological evaluation in drug dependence.
AB  - Psychological interventions are considered a central part of the individual
      psychotherapy in the rehabilitation counseling of psychiatrically symptomatic
      drug-dependent patients during methadone maintenance treatment in community
      programs. The need for psychological counseling should be evaluated for each
      individual patient. Medication is an important part of the treatment and
      individual psychotherapy focuses on the reduction or total cessation of drug use.
      The Recipient is G.M. 31, sentenced to a seven-year term of imprisonment for
      trafficking and use of and high-risk drugs, diagnosed on admission with opioid
      and methadone dependence, withdrawal syndrome. Following the observation and
      psychological evaluation, psychiatric and clinical examination, initiation of
      methadone substitution treatment was recommended, according to the following
      regimen: twelve 2.5 mg tablets for the first 2 days, followed by increase with
      about 5 mg per week until the complete remission of withdrawal symptoms,
      stabilization of the dose but not exceeding 200 mg methadone hydrochloride per
      day. Specialist monitoring, specialized counseling and individual and group
      psychotherapy were provided. 

PMID- 25870709
TI  - Combining tangential hydrodissection, panniculectomy, and negative pressure wound
      therapy in treating extensive degloving injury of the leg.
AB  - Major degloving injuries of the lower limb are daunting lesions because they are
      relatively rare and always produce larger soft tissue defects than direct visual
      inspection that could be predicted in the emergency room. Enough body of the
      medical literature supports the excision of the avulsed tissue and replaces it as
      a full-thickness skin graft. However, almost paradoxically, there is little
      support for the use of pristine large full-thickness skin graft in the treatment
      of these lesions. This article focuses on the use of tangential hydrodissection
      (VERSAJET Hydrosurgery System, Smith & Nephew) in preparing the avulsed wound and
      defatting of a large piece of full thickness skin graft taken from the abdomen by
      using a standard panniculectomy excision pattern and securing survival and
      integration of the graft with negative pressure wound therapy. The patient, a 60
      year-old obese and diabetic woman, suffered a roadside accident producing a
      degloving injury of her leg and was treated with the presented method; the final
      result was excellent and the reduction of the abdominal panniculus was a bonus. 

PMID- 25870710
TI  - Extracorporeal shockwave therapy (ESWT) benefits in spastic children with
      cerebral palsy (CP).
AB  - INTRODUCTION: ESWT refers to the use of Shock Waves in medical practice. It was
      used as an important tool in spasticity management of children with CP. The aim
      of our study was to evaluate the effect of a 3 session of ESWT on spastic upper
      and lower limbs muscles in children with CP. METHODS: Sixty-three children (37
      boys and 26 girls), mean age 99.57+/-53.74 months, were included in the study. We
      used focused ESWT, applied in 3 sessions during the admission of each child, on
      the mainly affected muscles, using the same parameters on all patients (energy -
      0.15 mJ/mm2, shot dose - 500 shocks/ session, frequency - 10 Hz). All patients
      were assessed two times: once, in admission (before any physical or ESWT
      appliance) and second, at discharge (after receiving the entire prescribed
      treatment), following: Modified Ashworth Scale (MAS), Gross Motor Function
      Classification System (GMFCS), Gross Motor Function Measure 66 (GMFM-66) and also
      a Questionnaire on Pain caused by spasticity (QPS). RESULTS: We found a better
      and significant decrease of MAS level in the ESWT treated group, thus leading to
      a concomitant decrease of QPS score and also increase of GMFM-66 score.
      CONCLUSION: ESWT, applied in 3 sessions, with 0.15 mJ/ mm2, using 500 shocks/ min
      and 10 Hz as frequency may decrease children spasticity level and pain caused by
      it and improve the gross motor function.

PMID- 25870711
TI  - Use of benzodiazepines and detoxification with methadone.
AB  - RATIONALE: Benzodiazepines are used as anti anxiety drugs, as well as in adjunct
      treatment for a range of neurological and psychiatric disorders. Abusive patterns
      of use were increasingly reported and building evidence points to prevalence of
      benzodiazepines abuse, on one hand as well as to their common abuse in
      combination with other drugs such as opioids, most frequently. OBJECTIVE: The
      main objective of this research is to conduct a systematic study on the behavior
      profile of a patient admitted to a prison hospital, who is a benzodiazepines user
      consecutive to admission into a methadone administration program. METHODS AND
      RESULTS: Statistic values have been taken into account describing the
      distribution and the distribution form of the various variables studied to find
      the normality degree of distributions, regarding three measurements at the three
      moments: before the administration of methadone, immediately after its completion
      and two months after completion. CONCLUSIONS AND DISCUSSIONS: The statistic
      results obtained speak of a strong positive correlation, allowing the support of
      the fact that persons diagnosed with prescribed/ unprescribed benzodiazepine, use
      the display association with the admission into a methadone administration
      program, based on the assumption which concerns a significant positive
      association between the use of reported benzodiazepine and the administration of
      methadone in the questioned patients on admission. As far as the second premise
      regarding the administration of methadone is concerned it brings about an
      improvement in the level of benzodiazepines used in research patients, which one
      may assert that, according to the results obtained, the initiation of methadone
      therapy in the detoxification program is conducive to the reduction of
      benzodiazepines use.

PMID- 25870712
TI  - Telesurgery--an efficient interdisciplinary approach used to improve the health
      care system.
AB  - At the time of the writing of this article, there are three operational
      telemedicine control centers in Bucharest, Targul-Mures, and Iasi; however, the
      current telemedicine infrastructure has limited geographic coverage and is
      exclusively used in the field of emergency medicine with only few promising
      beginnings in the domain of family medicine. Nevertheless, many areas of Romania
      are still lacking qualified medical personnel that can perform vital surgeries
      thus requiring patients to travel long distances to obtain the health care
      services they require. In order to improve the current healthcare infrastructure
      and eliminate the difficulties associated with a lack of qualified medical
      personnel in rural areas of the country, this article suggests the implementation
      of telesurgery as a practical solution. This article will hope to analyze the
      applicability of telesurgery by looking at the benefits and costs of creating a
      national telesurgery infrastructure, by predicting possible obstacles in creating
      such a system and by suggesting ways in which these obstacles can be avoided. The
      writing of this article was possible thanks to interviews, articles, and data
      obtained from surgeons and medical personnel that practice in Romania, the
      Republic of Moldova, Canada, and the United States of America. A vast majority of
      technical details has been furnished by the producers of robotic surgery
      platforms such as Intuitive Surgical(r). 

PMID- 25870714
TI  - Synthesis of biologically important neutral amylo-beta peptide by using improved
      Fmoc solid-phase peptide synthetic strategy.
AB  - The 10 amino acid sequence of the biologically important neutral amylo-beta
      peptide has equally hydrophilic and hydrophobic properties, which reduces the
      coupling efficiency during its synthesis and reduces the final yield of the
      peptide, and is therefore classified as a "difficult peptide sequence." The
      method presented here minimizes the synthetic problems by the introduction of
      improved Fmoc chemistry and effective hydroxybenzotriazole (HoBt),
      diisopropylcarbodiimide (DIC)-coupling and activation strategies. In addition, we
      developed a PS-TPGD resin as a solid support for the synthesis of specific
      neutral peptides, which is still a challenge to peptide chemistry. The most
      essential biologically active neutral amylo-beta peptide (KVKRIILARS) was
      successfully synthesized, and some synthetic modification was performed using the
      Fmoc solid-phase peptide synthesis (SPPS) method for purity and yield
      improvement. Graphical abstract?. 

PMID- 25870715
TI  - JOCB Bulletin.

PMID- 25870713
TI  - A review of characterization of tocotrienols from plant oils and foods.
AB  - Tocotrienols, members of the vitamin E family, are natural compounds found in a
      number of vegetable oils, wheat germ, barley and certain types of nuts and
      grains. Vegetable oils provide the best sources of these vitamin E forms,
      particularly palm oil and rice bran oil contain higher amounts of tocotrienols.
      Other sources of tocotrienols include grape fruit seed oil, oats, hazelnuts,
      maize, olive oil, buckthorn berry, rye, flax seed oil, poppy seed oil and
      sunflower oil. Tocotrienols are of four types, viz. alpha (alpha), beta (beta),
      gamma (gamma) and delta (delta). Unlike tocopherols, tocotrienols are unsaturated
      and possess an isoprenoid side chain. A number of researchers have developed
      methods for the extraction, analysis, identification and quantification of
      different types of vitamin E compounds. This article constitutes an in-depth
      review of the chemistry and extraction of the unsaturated vitamin E derivatives,
      tocotrienols, from various sources using different methods. This review article
      lists the different techniques that are used in the characterization and
      purification of tocotrienols such as soxhlet and solid-liquid extractions,
      saponification method, chromatography (thin layer, column chromatography, gas
      chromatography, supercritical fluid, high performance), capillary
      electrochromatography and mass spectrometry. Some of the methods described were
      able to identify one form or type while others could analyse all the analogues of
      tocotrienol molecules. Hence, this article will be helpful in understanding the
      various methods used in the characterization of this lesser known vitamin E
      variant. 

PMID- 25870716
TI  - Effects of citric Acid and desensitizing agent application on nonfluorosed and
      fluorosed dentin: an in vitro sem study.
AB  - Fluorosis is one of the factors which bring about mineralisation changes in a
      dentinal structure leading to dentin. The purpose of the present study was to
      compare and evaluate the dentinal tubular changes in fluorosed and nonfluorosed
      teeth subsequent to the application of citric acid,strontium acetate based sodium
      fluoride (SAF) using scanning electron microscopy (SEM). Dentin specimens from
      healthy fluorosed and nonfluorosed teeth were included in the study. Each of them
      was grouped into acid treated and SAF treatment groups. Using SEM, the
      photomicrographs (3500x) of dentin specimens were evaluated. Results showed while
      there was a significant difference in tubular width of partial occlusion <= 25%,
      being more in fluorosed group compared to nonfluorosed group after application
      SAF. Application of desensitising agents demonstrated higher number of dentinal
      tubular occlusion and diameter reduction in nonfluorosed dentin compared to
      fluorosed dentin. SUMMARY: Root biomodification and desensitising agent procedure
      brings in definite difference between fluorosed and non-fluorosed dentin
      specimens.

PMID- 25870717
TI  - Root Resorption a 6-Year Follow-up Case Report.
AB  - This paper describes the clinical course of a pediatric patient developing
      cervical external root resorption (CERR). An 11-year old male patient had
      sustained dental trauma and was diagnosed with crown fracture affecting the
      incisal and middle thirds of the maxillary right permanent central incisor and
      the maxillary right permanent lateral incisor with pulp exposure and CERR after
      24 months. Diagnosis and treatment of CERR are a challenge for dental
      practitioners. In this case, preservation of natural dentition is shown as a
      successful treatment in a 6-year follow-up. 

PMID- 25870718
TI  - Effect of fluoride and chlorhexidine digluconate mouthrinses on plaque biofilms.
AB  - OBJECTIVE: To develop a model in which to investigate the architecture of plaque
      biofilms formed on enamel surfaces in vivo and to compare the effects of anti
      microbial agents of relevance for caries on biofilm vitality. Materials and
      Methodology : Enamel discs mounted on healing abutments in the pre-molar region
      were worn by three subjects for 7 days. Control discs were removed before
      subjects rinsed with 0.1% chlorhexidine digluconate (CHX) or 0.2% sodium fluoride
      (NaF) for 1 minute. Biofilms were stained with Baclight Live/Dead and z-stacks of
      images created using confocal scanning laser micoscopy. The levels of vital and
      dead/damaged bacteria in the biofilms, assessed as the proportion of green and
      red pixels respectively, were analysed using ImageTrak((r)) software. Results :
      The subjects showed individual differences in biofilm architecture. The thickness
      of the biofilms varied from 28-96um although cell density was always the greatest
      in the middle layers. In control biofilms, the overall levels of vitality were
      high (71-98%) especially in the area closest to the enamel interface. Rinsing
      with either CHX or NaF caused a similar reduction in overall vitality. CHX
      exerted an effect throughout the biofilm, particularly on the surface of cell
      clusters whereas NaF caused cell damage/death mainly in the middle to lower
      biofilm layers. Conclusion : We describe a model that allows the formation of
      mature, undisturbed oral biofilms on human enamel surfaces in vivo and show that
      CHX and NaF have a similar effect on overall vitality but differ in their sites
      of action.

PMID- 25870719
TI  - Impact of Dynamic Loading on the Implant-abutment Interface Using a Gas-enhanced
      Permeation Test In Vitro.
AB  - PURPOSE: To assess implant leakage under static conditions as well as during and
      after dynamic loading. Materials and methods : Implants (Astra Tech (A), Biomet
      3i (B) and Nobel Biocare (C)) were evaluated for leakage (n=8/group). Testing to
      assess the gas pressure change over time (hPa/min) and infiltrated fluid volume,
      was performed in a Gas Enhanced Permeation Test (GEPT) to qualify embedding.
      Implant apexes were then drilled, abutments were mounted and resin build-ups were
      fabricated. GEPT was reassessed. Samples were afterward mounted in a computer
      controlled masticator while tested to bacterial leakage, they were daily observed
      for turbidity. Samples were then reassessed using GEPT. Dunnett's and Fisher's
      exact tests were utilized to compare implant and to analyze bacterial leakage.
      Results : Significant differences in GEPT values were shown after loading
      (p=0.034). Leakage resistance was best for B when compared to C (p=0.023).
      Samples with higher GEPT values demonstrated earlier bacterial leakage, occurring
      after 1 or 2 days (A=4, B=0, C=6) and showing favorability for implant system B
      (p=0.009). Conclusion : Implants leaking under static conditions had increased
      potential for bacterial leakage under dynamic conditions. As strongly correlating
      to sophisticated analytical methods, GEPT is a promising technique for assessing
      the overall implant system leakage resistance.

PMID- 25870720
TI  - On the meaning of chance in biology.
AB  - Chance has somewhat different meanings in different contexts, and can be taken to
      be either ontological (as in quantum indeterminacy) or epistemological (as in
      stochastic uncertainty). Here I argue that, whether or not it stems from physical
      indeterminacy, chance is a fundamental biological reality that is meaningless
      outside the context of knowledge. To say that something happened by chance means
      that it did not happen by design. This of course is a cornerstone of Darwin's
      theory of evolution: random undirected variation is the creative wellspring upon
      which natural selection acts to sculpt the functional form (and hence apparent
      design) of organisms. In his essay Chance & Necessity, Jacques Monod argued that
      an intellectually honest commitment to objectivity requires that we accord chance
      a central role in an otherwise mechanistic biology, and suggested that doing so
      may well place the origin of life outside the realm of scientific tractability.
      While that may be true, ongoing research on the origin of life problem suggests
      that abiogenesis may have been possible, and perhaps even probable, under the
      conditions that existed on primordial earth. Following others, I argue that the
      world should be viewed as causally open, i.e. primordially indeterminate or
      vague. Accordingly, chance ought to be the default scientific explanation for
      origination, a universal 'null hypothesis' to be assumed until disproven. In this
      framework, creation of anything new manifests freedom (allowing for chance), and
      causation manifests constraint, the developmental emergence of which establishes
      the space of possibilities that may by chance be realized.

PMID- 25870721
TI  - [Evaluation of liver function in severe malaria in children under five in
      Kinshasa, Democratic Republic of the Congo].

PMID- 25870722
TI  - [Study of clinical, sonographic and nutritional aspects of polycystic ovary
      syndrome (PCOS) in Mbuji-Mayi, DR Congo].

PMID- 25870723
TI  - [Metaplastic breast cancer: report of a case].

PMID- 25870724
TI  - Toxic epidermal necrolysis: a retrospective analysis of 17 cases from central
      Tunisia.
AB  - Toxic epidermal necrolysis (TEN), also known as Lyell's syndrome, is a rare, life
      threatening and wide-spread exfoliative disease of the skin and mucous membrane
      that is most commonly drug-induced. We retrospectively reviewed the charts of 17
      patients who suffered from TEN in Farhat Hached University Hospital, Sousse,
      Tunisia over a 19-year period from January 1994 to January 2013. Causality for
      suspected drugs was assessed by means of the Naranjo adverse drug reaction (ADR)
      probability scale. Antibiotics, mainly beta-lactams, were the most common
      implicated drugs, followed by nonsteroidal anti-inflammatory drugs,
      anticonvulsants, and allopurinol. The interval between drug intake and onset of
      the first symptom ranged between few hours and 19 days with a mean period of 6.11
      days. There was extensive skin detachment, averaging 66.17% of total body surface
      area (range 40-95%). The most major complication was infection, occurring in 9
      patients (53%). Seven patients died with a mortality rate of 41%. 

PMID- 25870725
TI  - [Small bowel perforation secondary to gallstone ileus: report of a case].

PMID- 25870726
TI  - [About three brothers with secondary gouty arthropathy due to a deficiency in
      Hypoxanthine-guanine phosphoribosyltransferase (HGPRT)].

PMID- 25870727
TI  - Factors affecting birth preparedness and complication readiness in Jimma Zone,
      Southwest Ethiopia: a multilevel analysis.
AB  - INTRODUCTION: Birth preparedness and complication readiness have been considered
      as comprehensive strategy aimed at promoting the timely utilization of skilled
      maternal health care. However, its status and affecting factors have not been
      well studied at different levels in the study area. Thus, this study was aimed to
      fill this gap by conducting community based study. METHODS: A cross-sectional
      study was conducted among randomly selected 3612 pregnant women from June
      September 2012. The data were collected by interviewer-administered structured
      questionnaire and analyzed by SPSS V.20.0 and STATA 13. Mixed-effects multilevel
      logistic regression model was used to identify factors affecting birth
      preparedness and complication readiness. RESULTS: The status of birth
      preparedness and complication readiness was 23.3% (95% CI: 21.8%, 24.9%). Being
      in urban residence and having health center within two hours distance were among
      the higher level factors increasing birth preparedness and complication
      readiness. Educational status of primary or above, husband's occupation of
      employed or merchant, third or above wealth quintiles, knowledge of key danger
      signs during labor, attitude and frequency of antenatal care visits were among
      the lower level factors found to increase the likelihood of preparation for birth
      and its complications. CONCLUSION: The status of birth preparedness and
      complication readiness was low in the study area. Both community level and
      individual level factors had important program implications. Socio demographic,
      economic, knowledge of key danger signs, attitude and antenatal care use were
      identified as associated factors. Improving antenatal care, giving special
      emphasis to danger signs and community based health education are recommended.

PMID- 25870728
TI  - [Skin manifestation of disseminated intravascular coagulopathy complicating an
      abortion].

PMID- 25870729
TI  - [Dermatofibrosarcoma protuberans: report of 38 cases].

PMID- 25870730
TI  - [Squamous cell carcinoma of the eyelid: management of an evolved form in a young
      patient].

PMID- 25870731
TI  - Factors associated with HIV voluntary disclosure of people living with HIV to
      their steady sexual partner in the Democratic Republic of the Congo: results from
      a community-based participatory research.
AB  - INTRODUCTION: HIV disclosure to a steady sexual partner (SSP) is important both
      in preventing HIV transmission and improving the quality of life of people living
      with HIV (PLHIV). Its determinants have been poorly investigated in the
      Democratic Republic of the Congo. The study objective was to determine factors
      independently associated with voluntary disclosure to one's SSP in PLHIV
      receiving services from a Congolese community-based organization (CBO). METHODS:
      A community-based participatory research was performed and 300 PLHIV were
      interviewed by members of the CBO, using a standardized questionnaire. A
      multivariate logistic regression was used to determine the variables
      independently associated with disclosure. RESULTS: In this sample, 79 of the 127
      participants (62%) included in the analysis declared having voluntarily disclosed
      their serostatus to their SSP. Declaring to be in a relationship (Odds Ratio (95%
      Confidence Interval): 4.2 (1.4-12.6)), having tested for HIV because of symptoms
      (2.5 (1.0-6.4)), having taken the test on one's own initiative (3.2 (1.3-8.0)),
      having felt sympathy and indifference from people when disclosing (6.0 (1.4-26.9)
      and 5.0 (1.1-22.8), respectively) as well as having a higher score of the
      "regular discussion about daily life with HIV" index (1.7 (1.1-2.5)) were
      significantly associated with disclosure to one's SSP. CONCLUSION: Several
      individual and contextual factors were associated with voluntary disclosure to
      SSP in this study, highlighting the complex nature of the disclosure process.
      Interventions encouraging disclosure should be designed so as to adapt to one's
      personal life with HIV as well as psychosocial environment.

PMID- 25870732
TI  - [Cavernous transformation of the portal vein in children: about 11 cases].

PMID- 25870733
TI  - Evaluation of the Notifiable diseases surveillance system in Sanyati district,
      Zimbabwe, 2010-2011.
AB  - INTRODUCTION: The Notifiable disease surveillance system (NDSS) was established
      in Zimbabwe through the Public Health Act. Between January and August 2011, 14
      dog bites were treated at Kadoma Hospital. Eighty-six doses of anti-rabies
      vaccine were dispensed. One suspected rabies case was reported, without
      epidemiological investigations. The discrepancy may imply under reporting of
      Notifiable Diseases. The study was conducted to evaluate the NDSS in Sanyati
      district. METHODS: A descriptive cross sectional study was conducted. Healthcare
      workers in selected health facilities in urban, rural, and private and public
      sector were interviewed using questionnaires. Checklists were used to assess
      resource availability and guide records review of notification forms. Epi
      Info(TM) was used to generate frequencies, proportions and Chi Square tests at 5%
      level. RESULTS: We recruited 69 participants, from 16 facilities. Twenty six
      percent recalled at least 9 Notifiable diseases, 72% correctly mentioned the T1
      form for notification, 39% correctly mentioned the forms completed in triplicate
      and 20% knew it was a legal requirement to notify. Ninety six percent of
      respondents indicated willingness to participate, whilst 41% had ever received
      feedback. Three out of 16 health facilities had T1 forms. CONCLUSION: NDSS is
      useful, acceptable, simple, and sensitive. NDSS is threatened by lack of T1
      forms, poor feedback and knowledge of health workers on NDSS. T1 forms and
      guidelines for completing the forms were distributed to all health facilities,
      public and private sector. On the job training of health workers through
      tutorials, supervision and feedback was conducted.

PMID- 25870734
TI  - Para testicular rhabdomyosarcoma in adults: three case reports and review of
      literature.
AB  - Paratesticular embryonal rhabdomyosarcoma (RMS) is a rare tumor arising from the
      mesenchymal tissues of the spermatic cord, epididymis, testis and testicular
      tunics. We report three cases of adult paratesticular RMS, two embryonic and one
      pleomorphic rhabdomyosarcoma. All the patients underwent diagnostic orchidectomy.
      The work up investigations revealed lung metastases. Chemotherapy with Ifosfamide
      and Doxorubicin was used in two cases, whereas Vincristin-Actinomycin D and
      Cyclophosphamide was received in one case. An objective partial response was
      reported in 2 cases, with complete response in one case. Paratesticular RMS is a
      rare and aggressive tumor. Because of the absence of protocols designed
      specifically for adult patients, it is necessary to follow therapeutic guidelines
      in pediatric protocols.

PMID- 25870735
TI  - [Acute disseminated encephalomyelitis in children].

PMID- 25870736
TI  - Why acute decreased vision in patients with high myopia is an emergency?

PMID- 25870737
TI  - Phlegmasia cerulea dolens: case report on a HIV-AIDS patient in a sub-saharian
      semi-urban practice.
AB  - Venous thromboembolism has also become a major health concern in sub-saharian
      Africa. Studies addressing at this issue are rare in Cameroon. Thus, the case
      reported here presents singular characteristics: its clinical form, phlegmasia
      cerulea dolens, a severe but uncommon complication of venous thromboembolism; and
      its infrequent recorded triggering factor, HIV-AIDS. 

PMID- 25870738
TI  - Unusual presentation of multiple nerve entrapment: a case report.
AB  - Cubital tunnel syndrome is the most common form of ulnar nerve entrapment and the
      second most common entrapment neuropathy of the upper extremity after carpal
      tunnel syndrome. However, bilateral compressive ulnar neuropathy is a rare
      condition. Electro diagnostic studies are a valid and reliable means of
      confirming the diagnosis. 

PMID- 25870739
TI  - High IgE sensitization to maize and rice pollen in the highlands of Madagascar.
AB  - INTRODUCTION: Maize and rice are two crops constituting the main food supply in
      many under-developed and developing countries. Despite the large area devoted to
      the culture, the sensitization to the pollen from these plants is reported to be
      low and often considered as an occupational allergy. METHODS: Sixty five Malagasy
      pollen allergic patients were clinically and immunochemically investigated with
      regard to maize and rice pollen allergens. Pollen extracts were
      electrophoretically separated in 1 and 2 dimensions and IgE and IgG reactivities
      detected upon immunoblotting. RESULTS: When exploring the sensitization profile
      of Malagasy allergic patients to maize and rice pollen, it appears that a high
      proportion of these patients consulting during grass pollinating season were
      sensitized to both pollen as revealed by skin prick testing (62 vs. 59%) and IgE
      immunoblotting (85 vs. 40%). Several clinically relevant allergens were
      recognized by patients' serum IgE in maize and rice pollen extracts. CONCLUSION:
      The high levels of maize and rice pollen sensitization should be related, in this
      tropical region, to a specific environmental exposure including i) a proximity of
      the population to the allergenic sources and ii) a putative exacerbating effect
      of a highly polluted urban atmosphere on pollen allergenicity. Cross-reactivities
      between wild and cultivated grasses and also between rice and maize pollen are
      involved as well as some specific maize sensitizations. The presence of dense
      urban and peri-urban agriculture, in various African regions and worldwide, could
      be a high environmental risk factor for people sensitive to maize pollen.

PMID- 25870740
TI  - [Sonographic study of the diameter of the sheath of the optic nerve in healthy
      black African children].

PMID- 25870741
TI  - [Evaluation of the level of knowledge of patients on treatment with vitamin K
      antagonists in Ouagadougou cardiology department].

PMID- 25870742
TI  - [Epidemiological, clinical and radiological profile of musculoskeletal disorders
      of hemophiliacs in Madagascar].

PMID- 25870743
TI  - Surgery of benign neurogenic tumors in adults: single institution experience.
AB  - The objective of this work is to review retrospectively our experience with 17
      patients presenting with benign neurogenic tumors, managed in the department of
      thoracic surgery, Mohamed V Military Academic Hospital, Rabat, Morocco. Between
      2003 and 2011, seventeen patients were surgically treated for benign neurogenic
      tumors of the mediastinum, among 112 mediastinal tumors operated during the same
      period. The mean age of the 17 patients was 46 years, including 11 females and 6
      males. The information about clinical presentation, diagnostic procedures,
      surgical techniques and postoperative follow-up were extracted and analyzed from
      medical records. Symptoms related to the tumor were found in 13 patients (76,4%).
      The posterior mediastinum was the principal location (16 cases: 94%). Intraspinal
      extension was shown through MRI in one case. Surgical extirpation was complete in
      all patients. There were no tumor-related deaths and no significant
      complications. There were 13 schwannomas, 2 neurofibromas and 2 ganglioneuromas.
      Neurogenic tumors of the mediastinum in adults are mostly benign. Their only
      treatment is surgical extirpation. Video-assisted thoracoscopic resection is
      currently the best approach in selected patients. 

PMID- 25870744
TI  - Plasma levels of some coagulation parameters in steady state HBSC disease
      patients.
AB  - INTRODUCTION: Sickle cell disease is a collection of autosomal recessive genetic
      disorders. It includes homozygous HbSS and double heterozygote combinations such
      as HbSC. Central and West Africa bears a significant burden of HbSC disease.
      METHODS: Prothrombin time (PT), activated partial thromboplastin time (APTT),
      fibrinogen concentration (FC) and platelet count (PC) were determined in 41 HbSC
      and HbSS patients in steady state along with 40 apparently healthy HbAA controls.
      One way ANOVA test was used to compare means; p values< 0.05 were considered
      statistically significant. RESULTS: There was no significant difference in mean
      PT for the study groups (p = 0.192). Mean PC was highest in HbSS patients: 445.7
      +/- 128.3 X 10 9/ L compared to HbSC: 330.0 +/- 97.7 X 10 9/ L and HbAA:245 +/-
      77.7 X 10 9/ L (p = 0.000). Mean APTT was 28.1 +/- 3.8 seconds in controls,24.1 +
      /- 66 seconds in HbSS patients and 21.8 +/- 3.8 seconds in HbSC patients (p =
      0.000). Mean FC in HbSS was 1.6 +/- 0.7 g/L, 3.2 +/- 0.6 g/L in HbSC and 2.9 +/-
      0.4 g/L in HbAA (p = 0.000). CONCLUSION: A significant difference exists in PC,
      APTT and FC in HbSC patients compared to HbSS patients and HbAA controls.
      Elevated FC and shortened APTT may play a role in complications more
      characteristic of HbSC such as retinopathy and osteonecrosis. These suggest HbSC
      is not merely a milder form of HbSS; both diseases should be seen as different
      entities with regards to approaches for management.

PMID- 25870745
TI  - The correlation between the presence of quorum sensing, toxin-antitoxin system
      genes and MIC values with ability of biofilm formation in clinical isolates of
      Pseudomonas aeruginosa.
AB  - INTRODUCTION: Pseudomonas aeruginosa is a Gram-negative bacterium that considered
      as important opportunistic human pathogen. One of the mechanisms that help
      bacteria to tolerate survival in adverse conditions and resistance to antibiotics
      is biofilm formation through quorum sensing (QS) signals and toxin-antitoxin (TA)
      systems. QS and TA are two systems that have important roles in biofilm
      formation. QS is a global regulatory mechanism that enable bacteria to
      communicate with each other by production of auto inducers (AI) molecules in
      population. Because of importance biofilm formation in P. aeruginosa infections,
      here, we studied frequency of QS and TA genes among clinical isolates of P.
      aeruginosa with ability of biofilm formation. MATERIALS AND METHODS: One hundred
      and forty clinical isolates of P. aeruginosa were collected from Tehran and Ilam
      hospitals. The isolates were identified by biochemical tests. Biofilm formation
      was evaluated by microplate method. After DNA extraction by boiling method, the
      frequency of QS genes (lasIR, rhlIR), and TA genes (mazEF, relBE, hipBA, ccdAB
      and mqsR) were analyzed by PCR. RESULTS: Our results showed that maximum
      resistance is related to aztreonam (72.85%) antibiotic. Most of isolates were
      able to produce biofilm (87.15%) and the majority of them formed strong biofilm
      (56.42%). PCR results showed that frequency of mazEF, relBE, hipBA, ccdAB, mqsR,
      lasIR and rhlIR genes were 85.71, 100, 1.42, 100, 57.14, 93.57 and 83.57 percent,
      respectively. CONCLUSION: Clinical isolates of P. aeruginosa had high ability to
      form biofilm, and QS and TA system genes among these isolates were very high
      (except hipBA genes). There are significaut correlation between biofilm for
      mation and present of QS and TA system genes.

PMID- 25870746
TI  - Multiplex real-time PCR assay for detection and differentiation of Bordetella
      pertussis and Bordetella parapertussis.
AB  - BACKGROUND AND OBJECTIVE: Rapid diagnosis of pertussis is important for the
      timely isolation of the infection source and early prevention measures among the
      contact persons, especially among non-vaccinated infants for whom pertussis is
      life-threatening. MATERIALS AND METHODS: Targets IS481, IS1001, BP0026 and human
      GAPDH gene were used to develop a multiplex real-time PCR assay based on the
      TaqMan technology for detection and identification of Bordetella pertussis and
      Bordetella parapertussis in clinical samples. A total of 121 human clinical
      specimens obtained within 2012-2013 were used to evaluate the multiplex real-time
      PCR assay. Clinical specimens were also tested for culture and conventional PCR.
      Sensitivity and specificity for culture, conventional PCR, and multiplex real
      time PCR were measured in comparison with a clinical standard for B. pertussis
      infection. RESULTS: The lower limit of detection (LLOD) of the multiplex assay
      was similar to the LLOD of each target in an individual assay format, which was
      approximately 1 genomic equivalent per reaction for IS481, IS1001 and 10 genomic
      equivalents per reaction for BP0026 target. When the B. pertussis assays were
      compared with a clinical standard for B. pertussis infection, sensitivity was 5,
      59 and 89% the specificity was 100, 100 and 100% for culture, conventional PCR,
      and multiplex real-time PCR, respectively. CONCLUSIONS: Developed multiplex real
      time PCR offers a fast tool with high sensitivity and specificity for the
      diagnosis of B. pertussis and B. parapertussis infections which is suitable for
      implementation in a routine laboratory diagnostics.

PMID- 25870747
TI  - Antiviral activity of monoterpenes beta-pinene and limonene against herpes
      simplex virus in vitro.
AB  - BACKGROUND AND OBJECTIVES: Essential oils are complex mixtures containing
      compounds of several different functional- group classes. Depending on the
      structure, we can distinguish monoterpenes, phenylpropanes, and other components.
      Here in this study two monoterpene compounds of essential oils, i.e. beta-pinene
      and limonene were examined for their antiviral activity against herpes simplex
      virus type 1 (HSV-1) in vitro. MATERIAL AND METHODS: All antiviral assays were
      performed using RC-37 cells. Cytotoxicity was determined in a neutral red assay,
      antiviral assays were performed with HSV-1 strain KOS. The mode of antiviral
      action was evaluated at different periods during the viral replication cycle.
      Acyclovir was used as positive antiviral control. RESULTS: Beta-pinenene and
      limonenen reduced viral infectivity by 100 %. The mode of antiviral action has
      been determined, only moderate antiviral effects were revealed by monoterpenes
      when these drugs were added to host cells prior infection or after entry of HSV
      into cells. However, both monoterpenes exhibited high anti-HSV-1 activity by
      direct interaction with free virus particles. Both tested drugs interacted with
      HSV-1 in a dose-dependent manner thereby inactivating viral infection.
      CONCLUSIONS: These results suggest that monoterpenes in essential oils exhibit
      antiherpetic activity in the early phase of viral multiplication and might be
      used as potential antiviral agents.

PMID- 25870748
TI  - Identification and characterization of class 1 integrons among atypical
      enteropathogenic Escherichia coli isolated from children under 5 years of age.
AB  - BACKGROUND AND OBJECTIVES: The therapeutic options for diseases caused by
      Escherichia coli are limited. In this study we investigated the presence of
      virulence factors among Enteropathogenic Escherichia coli (EPEC) strains and
      their antibiotic resistance patterns. The isolates were also checked for the
      presence of class1 integrons and gene cassettes. MATERIALS AND METHODS: This
      study included 70 EPEC strains isolated from children. Antimicrobial resistance
      patterns were determined using diffusion methods. The broth microdilution methods
      was used to determine the minimum inhibitory concentration. PCR was used to
      detect eaeA, bfpA genes. The 5' and 3' conserved sequences (CSs) of class 1
      integrons and intI gene were amplified to investigate the presence of integrons
      and gene cassettes. RESULTS: Antimicrobial susceptibility testing showed that 4
      (5.7%), 3 (4.2%), and 2 (2.8 %) isolates were resistant to ampicillin,
      trimethoprim-sulfamethoxazole, and ceftazidime, respectively. Resistance rates to
      ciprofloxacin and aztreonam were 1.4%. Thirteen (18.5%) isolates showed
      resistance to tetracycline, and 4 (5.7%) were kanamycin resistant. Class I
      integron detected in 22 (31.4%) isolates. All the gene cassettes found in class I
      integrons corresponded to different variants of dfr and aadA genes. CONCLUSION:
      Prevalence of class I integrons in EPEC strains was high. Presence of aadA and
      dfr gene cassettes in integrons represents high distribution of resistance
      determinants in EPEC strains.

PMID- 25870749
TI  - Prevalence and antimicrobial resistance pattern of methicillin resistant
      Staphylococcus aureus (MRSA) strains isolated from clinical specimens in Ardabil,
      Iran.
AB  - BACKGROUND AND OBJECTIVE: Reports on MRSA strains are increasing worldwide. The
      aim of this study was to find the prevalence of MRSA strains isolated from
      clinical specimens and to evaluate their resistance profile. Additionally we
      compared the phenotypic and genotypic methods for detection of methicillin
      resistance. MATERIALS AND METHODS: In this cross-sectional study, a total of 41
      isolates of S. aureus were collected from clinical specimens at two teaching
      hospitals in Ardabil, Iran. All isolates were identified at the species level by
      standard biochemical tests. The methicillin resistance were evaluated using three
      methods: PCR for mecA gene, agar dilution for determination of oxacillin MIC and
      disk diffusion test to detect methicillin, oxacillin and cefoxitin resistance.
      Antimicrobial resistance patterns were determined by disk diffusion method.
      RESULTS: The results identified 19 (46.3%) out of 41 isolates as MRSA. Most of
      the MRSA strains (68.4%) were isolated from patients hospitalized in ICU. All
      isolates were susceptible to vancomycin, mupirocin and linezolid. Among other
      antibiotics co-trimoxazole was more active against MRSA isolates. Using PCR as
      reference method all the phenotypic tests showed 100% specificity. The
      sensitivity for MIC test and cefoxitin was 100% and for methicillin and oxacillin
      disks was 77.7% and 89.5%, respectively. CONCLUSION: The prevalence of MRSA
      strains in our hospitals especially in ICU ward was high and disk diffusion
      testing using cefoxitin or oxacillin MIC test as an alternative to PCR for
      detection of MRSA is recommended.

PMID- 25870750
TI  - Characterization of Shiga-toxin producing E.coli (STEC) and enteropathogenic
      E.coli (EPEC) using multiplex Real-Time PCR assays for stx1 , stx2 , eaeA.
AB  - BACKGROUND AND OBJECTIVE: Diarrheal disease is still a major health problem,
      especially in developing countries, where it is considered as one of the leading
      causes of morbidity and mortality especially in children. Studies showed that
      Diarrheagenic E. coli (DEC) such as STES and EPEC strains are among the most
      prevalent causative agents in acute diarrhea, particularly in children. Aim of
      the present study was to investigate the presence and the frequency of STEC and
      EPEC as etiologic agent of diarrhea in children less than 2 years of age with
      diarrhea in Shiraz. MATERIALS AND METHODS: A total of 285 stool samples were
      collected from patients with diarrhea in Shiraz, in 2012. Diarrheagenic E. coli
      (DEC) strains were isolated by standard biochemical analysis. In this study, we
      used multiplex Real time PCR and single PCR to detect the presence of indicator
      genes stx1 , stx2 and eaeA for STEC and EPEC strains, respectively. RESULTS: A
      total of 285 stool samples were tested in which 49 (17%) were identified as
      contaminated with E. coli by biochemical tests. Out of total samples, 15 STEC
      (31%) and 13 EPEC (27%) were identified using multiplex Real-Time PCR assay.
      Among STEC isolates, 2 strains were stx1 (+), 8 isolates stx2 (+), 3 isolates
      were stx1 (+) , stx2 (+) and 2 isolates were stx1 (+) , stx2 (+), eaeA (+).
      CONCLUSION: In this study, we found rather high occurrence of STEC and EPEC
      virulence genes in children with diarrhea. The results of this study showed that,
      real time PCR can be used as a replacement for conventional PCR assay in the
      detecting virulence genes of STEC and EPEC strains. Real-time PCR offers the
      advantage of being a faster, more robust assay, because it does not require post
      PCR procedures to detect amplification products.

PMID- 25870751
TI  - Staphylococcus aureus nasal carriage in hemodialysis centers of Fez, Morocco.
AB  - BACKGROUND AND OBJECTIVES: Staphylococcus aureus (S. aureus) nasal carriage may
      be responsible for some serious infections in hemodialyzed patients. The main
      target of this study was to estimate the prevalence of S. aureus nasal carriage
      in hemodialysis outpatients and medical staff in hemodialysis centers
      specifically in Fez region. The second target is to identify the risks of
      colonization, resistance pattern of isolates and their virulence toxin genes.
      PATIENTS AND METHODS: Nasal swab specimens were obtained from 143 hemodialyzed
      outpatients and 32 medical staff from January to June 2012. Each participant
      completed a short questionnaire. Nasal carriage of S. aureus was demographically
      related (age, gender, hemodialysis duration), comorbidity (diabetes, malignancy)
      and exposure to health care (dialysis staff, hospitalization). PCR (Polymerase
      Chain Reaction) were used on all the isolates in the research of twelve
      staphylococcal enterotoxins genes. Also the PCR was used to investigate on the
      three factors epidermal cell differentiation inhibitors; three exfoliatin toxins;
      two leukotoxins; the toxic shock syndrome toxin-1 and the hemolysin beta genes.
      RESULTS: Nasal screening revealed 38.16%, 50% and 18.75% S. aureus carries in
      chronic, acute hemodialysis patients and medical staff, respectively. Only young
      participants were likely to be S. aureus carries (p = 0.002). But there were no
      gender differences between the isolate carriers and non-carriers or some
      comorbidity factors such as viral hepatitis B and C, HIV (Human Immunodeficiency
      Virus) infections, diabetes, chronic smoking, recent hospitalization or
      antibiotic therapy. Out of all isolates, only one (1.61%) was methicillin
      resistant and Twenty-one (33.87%) had at least two virulence toxin genes.
      CONCLUSIONS: Knowledge and monitoring of antibiotic resistance profile and
      virulence of S. aureus carriage are essential in the treatment of infections
      generated by this pathogen, as well as in the control of clonal dissemination and
      prevent the spread of S. aureus resistance.

PMID- 25870752
TI  - Evaluation of New ELISA based on rLsa63 - rLipL32 antigens for serodiagnosis of
      Human Leptospirosis.
AB  - BACKGROUND AND OBJECTIVES: Timely diagnosis of leptospirosis is essential for an
      effective treatment. Large diversity of clinical symptoms has led leptospirosis
      diagnosis difficult. Researchers have conducted many tests with wide-range of
      sensitivity and specificity to achieve novel diagnostic procedures which have
      higher sensitivity and specificity compared with previous tests and which are
      more reliable and available to public laboratories. This study aimed to introduce
      Lsa63 and LipL32 proteins-based ELISA tests with more sensitivity, specificity,
      accuracy and convenience for public laboratories. MATERIALS AND METHODS:
      Recombinant forms of Lsa63 and LipL32 proteins were first generated. After
      coating these proteins, IgM and IgG ELISA tests were performed. 220 patients with
      suspicion of leptospirosis infection were selected for serum collection. The sera
      tests were carried out using MAT, IgM and IgG ELISA tests. In order to assess the
      performance of ELISA, the results of this test were compared with MAT. RESULTS:
      30% of serum samples (n=65) in MAT were positive for leptospirosis infection,
      while ELISA tests including rLipL32- rLsa63-IgM and rLipL32-rLsa63-IgG showed
      40.45% (n=89) and 38.63% (n=80) positive reaction, respectively. CONCLUSION: Our
      results demonstrated that new ELISA tests based on mixing LipL32 and Lsa63
      proteins, a novel mixture of recombinant antigens, are valuable to detect
      specific antibodies against pathogenic Leptospira in human serum and could be
      considered as helpful techniques in leptospirosis diagnosis.

PMID- 25870753
TI  - Immunity to diphtheria and tetanus among blood donors in Arak, central province
      of Iran.
AB  - BACKGROUND AND OBJECTIVES: Tetanus and diphtheria are vaccine-preventable,
      infectious diseases with significant morbidity and mortality. Immunization by the
      diphtheria and tetanus toxoid (DT) has been applied in Iran for almost 50 years.
      However, there are very few data about the rate of immunity to these diseases in
      the adult population. the humoral immunity to tetanus and diphtheria among blood
      donors in Arak city, central provice of Iran were investigated. PATIENTS &
      METHODS: A total of 530 consecutive blood donor samples were collected from Blood
      Transfusion Organization, Central province of Iran. All samples were tested for
      diphteria and tetanus IgG antibodies using enzyme-linked immunosorbent assay
      (ELISA). RESULTS: From 530 cases, 91.9% were male and 8.1% were female. 99.6% of
      cases had protective levels of diphtheria antibody. Protective levels of tetanus
      antibody were found in 96% of subjects. There was not any significant difference
      between diphtheria and tetanus antibodies levels and age and sex. CONCLUSION: The
      obtained data showed that high proportion of the adult population in Arak have
      sufficient protection against diphtheria and tetanus. The high protective level
      of immunity to diphtheria and tetanus in Iran can be due to widespread use of
      booster vaccines in Iranian high schools and during the military services or for
      pregnant women in their 3(rd) trimester.

PMID- 25870754
TI  - The frequency of Neisseria gonorrhoeae endocervical infection among female
      carrier and changing trends of antimicrobial susceptibility patterns in Kashan,
      Iran.
AB  - BACKGROUND AND OBJECTIVES: Neisseria gonorrhoeae is the second most sexually
      transmitted diseases agents in developing countries. Antimicrobial resistance
      strains have created serious health concern. The aim of this study was to
      determine the frequency of endocervical gonococcal infection and antimicrobial
      susceptibility of N. gonorrhoeae in Kashan, Iran. MATERIALS AND METHODS: In this
      study, 294 endocervical swabs were collected from married women referred to the
      obstetrics and gynecology clinics in Kashan from December 2012 to May 2013. The
      samples were cultured in modified Thayer Martin in 37 degrees C with 5-10% CO2
      for 72 hours. Gram staining, oxidase, catalase and carbohydrate utilization tests
      were used to identify the isolated species. All isolates were tested for their
      susceptibilities to antimicrobials using the Kirby Bauer-disk diffusion
      techniques. RESULTS: N. gonorrhoeae was detected in 2.38% of studied cases (95%
      confidence interval [CI] 1.5-3.26%). All isolates were resistance to ceftriaxone,
      penicillin G, ciprofloxacin, cefepime, and two isolate (28.5%) showed
      intermediate sensitivity to tetracycline. CONCLUSION: Continued monitoring of
      prevalence of N. gonorrhoeae is important for preventing the dissemination of
      this microorganism. The present study emphasizes the importance of surveillance
      of antimicrobial resistance of N. gonorrhoeae in order to manage the rate of
      resistant strains and to revise the treatment policies.

PMID- 25870755
TI  - Structure of a TLR4-interacting SPA4 peptide.
AB  - We have recently identified a Toll-like receptor (TLR4)-interacting SPA4 peptide
      encoding amino acids: GDFRYSDGTPVNYTNWYRGE, a shorter region of human surfactant
      protein-A (SP-A). The SPA4 peptide suppressed lipopolysaccharide-induced
      inflammation (JPET 2011, Innate Immun 2013). In this report, we examined the
      structure of synthetic SPA4 peptide in solution by circular dichroism (CD) and
      nuclear magnetic resonance (NMR) spectroscopy. The CD analysis revealed that the
      SPA4 peptide is composed of ~35% beta sheet and <5% alpha helix. We used solution
      NMR to solve the structure of the SPA4 peptide. We calculated NMR structures
      using Nuclear Overhauser Enhancement (NOE) distance restraints. The superposition
      of the low energy structures indicated that the central 6-14 amino acids
      "SDGTPVNYT" of the 20mer SPA4 peptide form a turn, and amino acids on either side
      (GDFRY and NWYRGE) conform to flexible arms. Furthermore, thermal denaturation
      experiments demonstrated the structural flexibility of the peptide. The NMR
      structures of the SPA4 peptide align well with the homologous region within the
      available structure of rat SP-A and a computationally-docked model of SP-A-TLR4
      MD2 protein complex. Together, our results support the structural adaptability of
      SPA4 peptide for binding to TLR4.

PMID- 25870756
TI  - [Not Available].

PMID- 25870758
TI  - High performance computing enabling exhaustive analysis of higher order single
      nucleotide polymorphism interaction in Genome Wide Association Studies.
AB  - Genome-wide association studies (GWAS) are a common approach for systematic
      discovery of single nucleotide polymorphisms (SNPs) which are associated with a
      given disease. Univariate analysis approaches commonly employed may miss
      important SNP associations that only appear through multivariate analysis in
      complex diseases. However, multivariate SNP analysis is currently limited by its
      inherent computational complexity. In this work, we present a computational
      framework that harnesses supercomputers. Based on our results, we estimate a
      three-way interaction analysis on 1.1 million SNP GWAS data requiring over 5.8
      years on the full "Avoca" IBM Blue Gene/Q installation at the Victorian Life
      Sciences Computation Initiative. This is hundreds of times faster than estimates
      for other CPU based methods and four times faster than runtimes estimated for GPU
      methods, indicating how the improvement in the level of hardware applied to
      interaction analysis may alter the types of analysis that can be performed.
      Furthermore, the same analysis would take under 3 months on the currently largest
      IBM Blue Gene/Q supercomputer "Sequoia" at the Lawrence Livermore National
      Laboratory assuming linear scaling is maintained as our results suggest. Given
      that the implementation used in this study can be further optimised, this runtime
      means it is becoming feasible to carry out exhaustive analysis of higher order
      interaction studies on large modern GWAS. 

PMID- 25870757
TI  - Insights into temporal patterns of hospital patient safety from routinely
      collected electronic data.
AB  - BACKGROUND: The last two decades have seen an unprecedented growth in initiatives
      aimed to improve patient safety. For the most part, however, evidence of their
      impact remains controversial. At the same time, the healthcare industry has
      experienced an also unprecedented growth in the amount and variety of available
      electronic data. METHODS: In this paper, we provide a review of the use of
      routinely collected electronic data in the identification, analysis and
      surveillance of temporal patterns of patient safety. RESULTS: Two important
      temporal patterns of the safety of hospitalised patients were identified and
      discussed: long-term trends related to changes in clinical practice and
      healthcare policy; and shorter term patterns related to variations in workforce
      and resources. We found that consistency in reporting is intrinsically related to
      availability of large-scale, fit-for-purpose data. Consistent reported trends of
      patient harms included an increase in the incidence of post-operative sepsis and
      a decrease in central-line associated bloodstream infections. Improvement in the
      treatment of specific diseases, such as cardiac conditions, has also been
      demonstrated. Linkage of hospital data with other datasets provides essential
      temporal information about errors, as well as information about unsuspected
      system deficiencies. It has played an important role in the measurement and
      analysis of the effects of off-hours hospital operation. CONCLUSIONS: Measuring
      temporal patterns of patient safety is still inadequate with electronic health
      records not yet playing an important role. Patient safety interventions should
      not be implemented without a strategy for continuous monitoring of their effect.

PMID- 25870759
TI  - Automatic detection of tweets reporting cases of influenza like illnesses in
      Australia.
AB  - Early detection of disease outbreaks is critical for disease spread control and
      management. In this work we investigate the suitability of statistical machine
      learning approaches to automatically detect Twitter messages (tweets) that are
      likely to report cases of possible influenza like illnesses (ILI). Empirical
      results obtained on a large set of tweets originating from the state of Victoria,
      Australia, in a 3.5 month period show evidence that machine learning classifiers
      are effective in identifying tweets that mention possible cases of ILI (up to
      0.736 F-measure, i.e. the harmonic mean of precision and recall), regardless of
      the specific technique implemented by the classifier investigated in the study. 

PMID- 25870760
TI  - Design, implementation and operation of a multimodality research imaging
      informatics repository.
AB  - BACKGROUND: Biomedical imaging research increasingly involves acquiring, managing
      and processing large amounts of distributed imaging data. Integrated systems that
      combine data, meta-data and workflows are crucial for realising the opportunities
      presented by advances in imaging facilities. METHODS: This paper describes the
      design, implementation and operation of a multi-modality research imaging data
      management system that manages imaging data obtained from biomedical imaging
      scanners operated at Monash Biomedical Imaging (MBI), Monash University in
      Melbourne, Australia. In addition to Digital Imaging and Communications in
      Medicine (DICOM) images, raw data and non-DICOM biomedical data can be archived
      and distributed by the system. Imaging data are annotated with meta-data
      according to a study-centric data model and, therefore, scientific users can
      find, download and process data easily. RESULTS: The research imaging data
      management system ensures long-term usability, integrity inter-operability and
      integration of large imaging data. Research users can securely browse and
      download stored images and data, and upload processed data via subject-oriented
      informatics frameworks including the Distributed and Reflective Informatics
      System (DaRIS), and the Extensible Neuroimaging Archive Toolkit (XNAT).

PMID- 25870761
TI  - A platform for leveraging next generation sequencing for routine microbiology and
      public health use.
AB  - Even with the advent of next-generation sequencing (NGS) technologies which have
      revolutionised the field of bacterial genomics in recent years, a major barrier
      still exists to the implementation of NGS for routine microbiological use (in
      public health and clinical microbiology laboratories). Such routine use would
      make a big difference to investigations of pathogen transmission and
      prevention/control of (sometimes lethal) infections. The inherent complexity and
      high frequency of data analyses on very large sets of bacterial DNA sequence
      data, the ability to ensure data provenance and automatically track and log all
      analyses for audit purposes, the need for quick and accurate results, together
      with an essential user-friendly interface for regular non-technical laboratory
      staff, are all critical requirements for routine use in a public health setting.
      There are currently no systems to answer positively to all these requirements, in
      an integrated manner. In this paper, we describe a system for sequence analysis
      and interpretation that is highly automated and tackles the issues raised
      earlier, and that is designed for use in diagnostic laboratories by healthcare
      workers with no specialist bioinformatics knowledge. 

PMID- 25870762
TI  - Basic surgical skills course - Why is it so costly?
AB  - *Courses can be expensive and are often criticised for the transparency of
      associated costs.*It is important to appreciate the organisational costs of
      running high quality courses.*The three Royal Colleges in the UK do not use
      courses as profit making vehicles. 

PMID- 25870763
TI  - Do habits always override intentions? Pitting unhealthy snacking habits against
      snack-avoidance intentions.
AB  - BACKGROUND: Habit is defined as a process whereby an impulse towards behaviour is
      automatically initiated upon encountering a setting in which the behaviour has
      been performed in the past. A central tenet of habit theory is that habit
      overrides intentional tendencies in directing behaviour, such that as habit
      strength increases, intention becomes less predictive of behaviour. Yet, evidence
      of this effect has been methodologically limited by modelling the impact of
      positively-correlated habits and intentions. This study sought to test the effect
      of habits for unhealthy snacking on the relationship between intentions to avoid
      unhealthy snacks and snack intake. METHODS: Methods were chosen to match those
      used in studies that have shown habit-intention interactions. 239 adults
      completed valid and reliable measures of habitual snacking and intention to avoid
      snacking at baseline, and a self-report measure of snack intake two weeks later.
      Data were analysed using multiple regression. RESULTS: While both habit and
      intention independently predicted snack intake, no interaction between habit and
      intention was found. CONCLUSIONS: No support was found for the expected
      moderating impact of habit on the intention-behaviour relationship, indicating
      that individuals with intentions can act on those intentions despite having
      habits. Previous evidence of a habit-intention interaction effect may be
      unreliable. A growing literature indicates that habitual tendencies can be
      inhibited, albeit with difficulty. Habits and intentions may vary in the
      influence they exert over discrete behaviour instances. While the aggregation of
      behaviours across instances and individuals used in our study reflects the
      dominant methodology in habit research, it precludes examination of effects of in
      situ habits and intentions. More sophisticated data collection and analysis
      methods may be needed to better understand potential habit-intention
      interactions.

PMID- 25870764
TI  - Who's been framed? Framing effects are reduced in financial gambles made for
      others.
AB  - BACKGROUND: Decisions made on behalf of other people are sometimes more rational
      than those made for oneself. In this study we used a monetary gambling task to
      ask if the framing effect in decision-making is reduced in surrogate decision
      making. METHODS: Participants made a series of choices between a predetermined
      sure option and a risky gambling option of winning a proportion of an initial
      stake. Trials were presented as either a gain or a loss relative to that initial
      stake. In half of the trials participants made choices to earn money for
      themselves and in the other half they earned money for another participant.
      Framing effects were measured as risk seeking in loss frames and risk aversion in
      gain frames. RESULTS: Significant framing effects were observed both in trials in
      which participants earned money for themselves and those in which they earned
      money for another person; however, these framing effects were significantly
      reduced when making decisions for another person. It appears that the reduced
      emotional involvement when the decision-maker is not affected by the outcome of
      the decision thus lessens the framing effect without eradicating it altogether.
      CONCLUSIONS: This suggests that the deviation from rational choices in decision
      making can be significantly reduced when the emotional impact on the decision
      maker is lessened. These results are discussed in relation to Somatic Distortion
      Theory.

PMID- 25870765
TI  - Relationship between cold pressor pain-sensitivity and sleep quality in opioid
      dependent males on methadone treatment.
AB  - Aim. Poor sleep quality due to pain has been reported among opioid-dependent male
      patients on methadone maintenance therapy (MMT) but objective pain data are
      lacking. This study aimed to investigate the rate of pain-sensitivity using cold
      pressor test (CPT) and the relationship between pain-sensitivity and sleep
      quality in this population. Methods. A total of 168 male participants were
      included into the study. Objective pain-tolerance was evaluated at 0 h and at 24
      h after the first CPT. Malay version of the Pittsburgh Sleep Quality Index (PSQI)
      and the subjective opiate withdrawal scale (SOWS) questionnaires were
      administered to evaluate the quality of sleep and withdrawal symptoms,
      respectively. Results. The mean age of study participants was 37.22 (SD 6.20)
      years old. Mean daily methadone dose was 76.64 (SD 37.63) mg/day, mean global
      PSQI score was 5.47 (SD 2.74) and mean averaged SOWS score was 5.43 (SD 6.91).
      The averaged pain-tolerance time ranged from 7 to 300 s with a mean time of 32.16
      (SE 2.72) s, slightly below the cut-off score of 37.53 s. More specifically,
      78.6% (n = 132) of participants were identified as pain-sensitive (averaged pain
      tolerance time <=37.53 s), and 36 (21.4%) participants were pain-tolerant
      (averaged pain-tolerance time >37.53 s). The pain-sensitive group reported poorer
      sleep quality with mean (SD) PSQI of 5.78 (2.80) compared with the pain-tolerant
      group with mean (SD) PSQI of 4.31 (2.18) (p = 0.005). With analysis of
      covariance, pain-sensitive group was found to have higher global PSQI scores
      (adjusted mean 5.76, 95% CI 5.29; 6.22) than pain-tolerant participants (adjusted
      mean 4.42, 95% CI 3.52; 5.32) (p = 0.010). Conclusions. Majority of opioid
      dependent male patients on methadone treatment are pain-sensitive with CPT. Poor
      sleep quality is associated with cold pressor pain-sensitivity. Pain and sleep
      complaints in this male population should not be overlooked. 

PMID- 25870766
TI  - A specimen-level phylogenetic analysis and taxonomic revision of Diplodocidae
      (Dinosauria, Sauropoda).
AB  - Diplodocidae are among the best known sauropod dinosaurs. Several species were
      described in the late 1800s or early 1900s from the Morrison Formation of North
      America. Since then, numerous additional specimens were recovered in the USA,
      Tanzania, Portugal, and Argentina, as well as possibly Spain, England, Georgia,
      Zimbabwe, and Asia. To date, the clade includes about 12 to 15 nominal species,
      some of them with questionable taxonomic status (e.g., 'Diplodocus' hayi or
      Dyslocosaurus polyonychius), and ranging in age from Late Jurassic to Early
      Cretaceous. However, intrageneric relationships of the iconic, multi-species
      genera Apatosaurus and Diplodocus are still poorly known. The way to resolve this
      issue is a specimen-based phylogenetic analysis, which has been previously
      implemented for Apatosaurus, but is here performed for the first time for the
      entire clade of Diplodocidae. The analysis includes 81 operational taxonomic
      units, 49 of which belong to Diplodocidae. The set of OTUs includes all name
      bearing type specimens previously proposed to belong to Diplodocidae, alongside a
      set of relatively complete referred specimens, which increase the amount of
      anatomically overlapping material. Non-diplodocid outgroups were selected to test
      the affinities of potential diplodocid specimens that have subsequently been
      suggested to belong outside the clade. The specimens were scored for 477
      morphological characters, representing one of the most extensive phylogenetic
      analyses of sauropod dinosaurs. Character states were figured and tables given in
      the case of numerical characters. The resulting cladogram recovers the classical
      arrangement of diplodocid relationships. Two numerical approaches were used to
      increase reproducibility in our taxonomic delimitation of species and genera.
      This resulted in the proposal that some species previously included in well-known
      genera like Apatosaurus and Diplodocus are generically distinct. Of particular
      note is that the famous genus Brontosaurus is considered valid by our
      quantitative approach. Furthermore, "Diplodocus" hayi represents a unique genus,
      which will herein be called Galeamopus gen. nov. On the other hand, these
      numerical approaches imply synonymization of "Dinheirosaurus" from the Late
      Jurassic of Portugal with the Morrison Formation genus Supersaurus. Our use of a
      specimen-, rather than species-based approach increases knowledge of
      intraspecific and intrageneric variation in diplodocids, and the study
      demonstrates how specimen-based phylogenetic analysis is a valuable tool in
      sauropod taxonomy, and potentially in paleontology and taxonomy as a whole. 

PMID- 25870767
TI  - Hydrogen-water enhances 5-fluorouracil-induced inhibition of colon cancer.
AB  - Oxidative stress is involved in cancer development. Hydrogen (H2) is a potent
      antioxidant and exhibits anti-inflammatory and potentially anticancer-like
      activities. This study aimed to investigate the role of H2 incombination with 5
      fluorouracil (5-FU) in cancer treatment both in vitro and in vivo using the colon
      26 cell line. The survival rate was determined using the Kaplan-Meier survival
      test, and cell viability was assessed using cell viability imaging kit and the
      MTT assay, and activation of the cell apoptosis pathway (Phosphorylated adenosine
      monophosphate activated protein kinase (p-AMPK), Apoptosis-inducing factor (AIF)
      and Caspase 3) were characterized by western blots. Hydrogen water administration
      improved the survival of mice with colon 26-induced cancer. Furthermore, hydrogen
      water enhanced cell apoptosis in cancer cells, resulting in a marked increase in
      the expression of p-AMPK, AIF and Caspase 3 in colon 26 cells. Hydrogen water
      also increased the inhibitory effect of 5-FU on colon 26 cells with spect to cell
      survival rate and anticancer functions. Additionally, high-content hydrogen water
      exhibited stronger antioxidative and anticancer activity than did the natural
      hydrogen water. In conclusion, high-content hydrogen water can inhibit colon
      cancer, particularly in combination with 5-fluorouracil. 

PMID- 25870768
TI  - A questions-based investigation of consumer mental-health information.
AB  - Despite the wealth of mental-health information available online to consumers,
      research has shown that the mental-health information needs of consumers are not
      being met. This study contributes to that research by soliciting consumer
      questions directly, categorizing them, analyzing their form, and assessing the
      extent to which they can be answered from a trusted and vetted source of online
      information, namely the website of the US National Institute of Mental Health
      (NIMH). As an alternative to surveys and analyses of online activity, this study
      shows how consumer questions provide new insight into what consumers do not know
      and how they express their information needs. The study crowdsourced 100 consumer
      questions through Amazon Inc.'s Mechanical Turk. Categorization of the questions
      shows broad agreement with earlier studies in terms of the content of consumer
      questions. It also suggests that consumers' grasp of mental health issues may be
      low compared to other health topics. The majority of the questions (74%) were
      simple in form, with the remainder being multi-part, multifaceted or narrative.
      Even simple-form questions could, however, have complex interpretations. Fifty
      four questions were submitted to the search box at the NIMH website. For 32
      questions, no answer could be found in the top one to three documents returned.
      Inadequacies in the search and retrieval technology deployed at websites account
      for some of the failure to find answers. The nature of consumer questions in
      mental health also plays a role. A question that has a false presupposition is
      less likely to have an answer in trusted and vetted sources of information.
      Consumer questions are also expressed with a degree of specificity that makes the
      retrieval of relevant information difficult. The significance of this study is
      that it shows what an analysis of consumer mental-health questions can tell us
      about consumer information needs and it provides new insight into the
      difficulties facing consumers looking for answers to their questions in online
      resources. 

PMID- 25870769
TI  - Models of knot and stem development in black spruce trees indicate a shift in
      allocation priority to branches when growth is limited.
AB  - The branch autonomy principle, which states that the growth of individual
      branches can be predicted from their morphology and position in the forest canopy
      irrespective of the characteristics of the tree, has been used to simplify models
      of branch growth in trees. However, observed changes in allocation priority
      within trees towards branches growing in light-favoured conditions, referred to
      as 'Milton's Law of resource availability and allocation,' have raised questions
      about the applicability of the branch autonomy principle. We present models
      linking knot ontogeny to the secondary growth of the main stem in black spruce
      (Picea mariana (Mill.) B.S.P.), which were used to assess the patterns of
      assimilate allocation over time, both within and between trees. Data describing
      the annual radial growth of 445 stem rings and the three-dimensional shape of
      5,377 knots were extracted from optical scans and X-ray computed tomography
      images taken along the stems of 10 trees. Total knot to stem area increment
      ratios (KSR) were calculated for each year of growth, and statistical models were
      developed to describe the annual development of knot diameter and curvature as a
      function of stem radial increment, total tree height, stem diameter, and the
      position of knots along an annual growth unit. KSR varied as a function of tree
      age and of the height to diameter ratio of the stem, a variable indicative of the
      competitive status of the tree. Simulations of the development of an individual
      knot showed that an increase in the stem radial growth rate was associated with
      an increase in the initial growth of the knot, but also with a shorter lifespan.
      Our results provide support for 'Milton's Law,' since they indicate that
      allocation priority is given to locations where the potential return is the
      highest. The developed models provided realistic simulations of knot morphology
      within trees, which could be integrated into a functional-structural model of
      tree growth and above-ground resource partitioning. 

PMID- 25870770
TI  - Widespread mitovirus sequences in plant genomes.
AB  - The exploration of the evolution of RNA viruses has been aided recently by the
      discovery of copies of fragments or complete genomes of non-retroviral RNA
      viruses (Non-retroviral Endogenous RNA Viral Elements, or NERVEs) in many
      eukaryotic nuclear genomes. Among the most prominent NERVEs are partial copies of
      the RNA dependent RNA polymerase (RdRP) of the mitoviruses in plant mitochondrial
      genomes. Mitoviruses are in the family Narnaviridae, which are the simplest
      viruses, encoding only a single protein (the RdRP) in their unencapsidated viral
      plus strand. Narnaviruses are known only in fungi, and the origin of plant
      mitochondrial mitovirus NERVEs appears to be horizontal transfer from plant
      pathogenic fungi. At least one mitochondrial mitovirus NERVE, but not its nuclear
      copy, is expressed. 

PMID- 25870771
TI  - Low cost audiovisual playback and recording triggered by radio frequency
      identification using Raspberry Pi.
AB  - Playbacks of visual or audio stimuli to wild animals is a widely used
      experimental tool in behavioral ecology. In many cases, however, playback
      experiments are constrained by observer limitations such as the time observers
      can be present, or the accuracy of observation. These problems are particularly
      apparent when playbacks are triggered by specific events, such as performing a
      specific behavior, or are targeted to specific individuals. We developed a low
      cost automated playback/recording system, using two field-deployable devices:
      radio-frequency identification (RFID) readers and Raspberry Pi micro-computers.
      This system detects a specific passive integrated transponder (PIT) tag attached
      to an individual, and subsequently plays back the stimuli, or records audio or
      visual information. To demonstrate the utility of this system and to test one of
      its possible applications, we tagged female and male tree swallows (Tachycineta
      bicolor) from two box-nesting populations with PIT tags and carried out playbacks
      of nestling begging calls every time focal females entered the nestbox over a six
      hour period. We show that the RFID-Raspberry Pi system presents a versatile, low
      cost, field-deployable system that can be adapted for many audio and visual
      playback purposes. In addition, the set-up does not require programming
      knowledge, and it easily customized to many other applications, depending on the
      research questions. Here, we discuss the possible applications and limitations of
      the system. The low cost and the small learning curve of the RFID-Raspberry Pi
      system provides a powerful new tool to field biologists. 

PMID- 25870772
TI  - Models for the directed evolution of bacterial allelopathy: bacteriophage lysins.
AB  - Microbes produce a variety of compounds that are used to kill or suppress other
      species. Traditional antibiotics have their origins in these natural products, as
      do many types of compounds being pursued today in the quest for new antibacterial
      drugs. When a potential toxin can be encoded by and exported from a species that
      is not harmed, the opportunity exists to use directed evolution to improve the
      toxin's ability to kill other species-allelopathy. In contrast to the typical
      application of directed evolution, this case requires the co-culture of at least
      two species or strains, a host that is unharmed by the toxin plus the intended
      target of the toxin. We develop mathematical and computational models of this
      directed evolution process. Two contexts are considered, one with the toxin
      encoded on a plasmid and the other with the toxin encoded in a phage. The plasmid
      system appears to be more promising than the phage system. Crucial to both
      designs is the ability to co-culture two species/strains (host and target) such
      that the host is greatly outgrown by the target species except when the target
      species is killed. The results suggest that, if these initial conditions can be
      satisfied, directed evolution is feasible for the plasmid-based system. Screening
      with a plasmid-based system may also enable rapid improvement of a toxin. 

PMID- 25870773
TI  - Does polyandry really pay off? The effects of multiple mating and number of
      fathers on morphological traits and survival in clutches of nesting green turtles
      at Tortuguero.
AB  - Despite the long debate of whether or not multiple mating benefits the offspring,
      studies still show contradictory results. Multiple mating takes time and energy.
      Thus, if females fertilize their eggs with a single mating, why to mate more than
      once? We investigated and inferred paternal identity and number of sires in 12
      clutches (240 hatchlings) of green turtles (Chelonia mydas) nests at Tortuguero,
      Costa Rica. Paternal alleles were inferred through comparison of maternal and
      hatchling genotypes, and indicated multiple paternity in at least 11 of the
      clutches (92%). The inferred average number of fathers was three (ranging from 1
      to 5). Moreover, regression analyses were used to investigate for correlation of
      inferred clutch paternity with morphological traits of hatchlings fitness
      (emergence success, length, weight and crawling speed), the size of the mother,
      and an environmental variable (incubation temperature). We suggest and propose
      two different comparative approaches for evaluating morphological traits and
      clutch paternity, in order to infer greater offspring survival. First, clutches
      coded by the exact number of fathers and second by the exact paternal
      contribution (fathers who gives greater proportion of the offspring per nest). We
      found significant differences (P < 0.05) in clutches coded by the exact number of
      fathers for all morphological traits. A general tendency of higher values in
      offspring sired by two to three fathers was observed for the length and weight
      traits. However, emergence success and crawling speed showed different trends
      which unable us to reach any further conclusion. The second approach analysing
      the paternal contribution showed no significant difference (P > 0.05) for any of
      the traits. We conclude that multiple paternity does not provide any extra
      benefit in the morphological fitness traits or the survival of the offspring,
      when analysed following the proposed comparative statistical methods. 

PMID- 25870774
TI  - Association between virtues and posttraumatic growth: preliminary evidence from a
      Chinese community sample after earthquakes.
AB  - Objective. Relationship, vitality, and conscientiousness are three fundamental
      virtues that have been recently identified as important individual differences to
      health, well being, and positive development. This cross-sectional study
      attempted to explore the relationship between the three constructs and post
      traumatic growth (PTG) in three directions, including indirect trauma samples
      without post-traumatic stress disorder (PTSD), direct trauma samples without
      PTSD, and direct trauma samples with PTSD. Methods. A total of 340 community
      participants from Sichuan Province, Mainland China involved in the study, most of
      which experienced Wenchuan and Lushan Earthquake. Participants were required to
      complete the self-reported questionnaire packages at one time point for obtaining
      their scores on virtues (Chinese Virtues Questionnaire), PTSD (PTSD Checklist
      Specific), and PTG (Post-traumatic Growth Inventory-Chinese). Results.
      Significant and positive correlations between the three virtues and PTG were
      identified (r = .39-.56; p < .01). Further regression analysis by stepwise method
      reveled that: in the indirect trauma samples, vitality explained 32% variance of
      PTG. In reference to the direct trauma sample without PTSD, both relationship and
      conscientiousness explained 32% variance of PTG, whereas in the direct trauma
      sample with PTSD, only conscientiousness accounted for 31% the variance in PTG.
      Conclusion.This cross-sectional investigation partly revealed the roles of
      different virtues in trauma context. Findings suggest important implications for
      strengths-based treatment. 

PMID- 25870775
TI  - Pre- and postmortem tyrannosaurid bite marks on the remains of Daspletosaurus
      (Tyrannosaurinae: Theropoda) from Dinosaur Provincial Park, Alberta, Canada.
AB  - Trace marks on the bones of non-avian dinosaurs may relate to feeding by large
      carnivores or as a result of combat. Here the cranium and mandible of a specimen
      of Daspletosaurus are described that show numerous premortem injuries with
      evidence of healing and these are inferred to relate primarily to intraspecific
      combat. In addition, postmortem damage to the mandible is indicative of late
      stage carcass consumption and the taphonomic context suggests that this was
      scavenging. These postmortem bites were delivered by a large bodied tyrannosaurid
      theropod and may have been a second Daspletosaurus, and thus this would be an
      additional record of tyrannosaurid cannibalism. 

PMID- 25870776
TI  - Laser photogrammetry improves size and demographic estimates for whale sharks.
AB  - Whale sharks Rhincodon typus are globally threatened, but a lack of biological
      and demographic information hampers an accurate assessment of their vulnerability
      to further decline or capacity to recover. We used laser photogrammetry at two
      aggregation sites to obtain more accurate size estimates of free-swimming whale
      sharks compared to visual estimates, allowing improved estimates of biological
      parameters. Individual whale sharks ranged from 432-917 cm total length (TL)
      (mean +/- SD = 673 +/- 118.8 cm, N = 122) in southern Mozambique and from 420-990
      cm TL (mean +/- SD = 641 +/- 133 cm, N = 46) in Tanzania. By combining
      measurements of stranded individuals with photogrammetry measurements of free
      swimming sharks, we calculated length at 50% maturity for males in Mozambique at
      916 cm TL. Repeat measurements of individual whale sharks measured over periods
      from 347-1,068 days yielded implausible growth rates, suggesting that the growth
      increment over this period was not large enough to be detected using laser
      photogrammetry, and that the method is best applied to estimating growth rates
      over longer (decadal) time periods. The sex ratio of both populations was biased
      towards males (74% in Mozambique, 89% in Tanzania), the majority of which were
      immature (98% in Mozambique, 94% in Tanzania). The population structure for these
      two aggregations was similar to most other documented whale shark aggregations
      around the world. Information on small (<400 cm) whale sharks, mature
      individuals, and females in this region is lacking, but necessary to inform
      conservation initiatives for this globally threatened species. 

PMID- 25870777
TI  - DNA quantification of basidiomycetous fungi during storage of logging residues.
AB  - The demand for bioenergy caused an increased use of logging residues, branches
      and treetops that were previously left on the ground after harvesting. Residues
      are stored outdoors in piles and it is unclear to what extent fungi transform
      this material. Our objective was to quantify the amount of wood degrading fungi
      during storage using quantitative real-time PCR (qPCR) to detect basidiomycetous
      DNA in logging residues, a novel approach in this field. We found that the qPCR
      method was accurate in quantifying the fungal DNA during storage. As the moisture
      content of the piled logging residues decreased during the storage period, the
      fungal DNA content also decreased. Scots pine residues contained more fungal DNA
      than residues from Norway spruce. Loose piles had generally more fungal DNA than
      bundled ones. 

PMID- 25870778
TI  - Reducing workplace burnout: the relative benefits of cardiovascular and
      resistance exercise.
AB  - Objectives. The global burden of burnout cost is in excess of $300 billion
      annually. Locally, just under half of working Australians experience high levels
      of occupational burnout. Consequently, burnout interventions are paramount to
      organisational productivity. Exercise has the potential to provide a multilevel
      and cost effective burnout intervention. The current study aims to extend the
      literature by comparing cardiovascular with resistance exercise to assess their
      relative effectiveness against well-being, perceived stress, and burnout. Design.
      Participants were 49 (36 females and 13 males) previously inactive volunteers
      ranging in age from 19 to 68 that completed a four week exercise program of
      either cardiovascular, resistance, or no exercise (control). Randomised control
      trial design was employed. Method. Participants were measured against the
      Subjective Exercise Experience Scale, the Perceived Stress Scale, and the Maslach
      Burnout Inventory. Results. After four weeks of exercise participants had greater
      positive well-being and personal accomplishment, and concomitantly less
      psychological distress, perceived stress, and emotional exhaustion.
      Cardiovascular exercise was found to increase well-being and decrease
      psychological distress, perceived stress, and emotional exhaustion. Resistance
      training was noticeably effective in increasing well-being and personal
      accomplishment and to reduce perceived stress. The present findings revealed
      large effect sizes suggesting that exercise may be an effective treatment for
      burnout. However, given a small sample size further research needs to be
      conducted. Conclusion. Exercise has potential to be an effective burnout
      intervention. Different types of exercise may assist employees in different ways.
      Organisations wishing to proactively reduce burnout can do so by encouraging
      their employees to access regular exercise programs. 

PMID- 25870779
TI  - A field based study of swimbladder adjustment in a physostomous teleost fish.
AB  - The present study assesses swimbladder dynamics in natural occurring sardine,
      Sardina pilchardus, populations with the aim to examine whether this is affected
      by bathymetric positioning and the physiological state of the individuals. To do
      so, swimbladder size and shape were modeled in relation to catch depth and the
      size of various visceral compartments such as gonad, liver, fat and stomach.
      Swimbladder size was shown to be related to depth in a way that individuals with
      smaller swimbladders occurred at larger depths. Moreover, evidence is provided
      that the swimbladder in sardine might have a functional relationship both with
      the reproductive and the feeding state of individuals, since none of the fish
      with hydrated gonads and/or large stomachs displayed distended swimbladders. 

PMID- 25870780
TI  - Reversible mechanical switching of magnetic interactions in a molecular shuttle.
AB  - Invited for this months cover are the groups of Professors Marco Lucarini and
      Alberto Credi at the University of Bologna. The cover picture shows coupled and
      uncoupled states of a [2]rotaxane incorporating stable nitroxide radical units in
      both the ring and dumbbell components. Interaction between nitroxide radicals
      could be switched between noncoupled (three-line electron paramagnetic resonance
      (EPR) spectrum) and coupled (five-line EPR spectrum) upon deprotonation of the
      rotaxane NH2 (+) centers that effects a quantitative displacement of a
      dibenzocrown macroring to a 4,4'-bipyridinium recognition site. The complete base
      and acid-induced switching cycle of the EPR pattern was repeated several times
      without an appreciable loss of signal, highlighting the reversibility of the
      process. Hence, this molecular machine is capable of switching on/off magnetic
      interactions by chemically driven reversible mechanical effects. For more
      details, see the Communication on p. 18 ff. 

PMID- 25870781
TI  - Graphical Abstract: ChemistryOpen 1/2015.

PMID- 25870782
TI  - Spotlights on our sister journals: ChemistryOpen 1/2015.

PMID- 25870783
TI  - Evaluation of the diagnostic value of alpha-l-fucosidase, alpha-fetoprotein and
      thymidine kinase 1 with ROC and logistic regression for hepatocellular carcinoma.
AB  - The purpose of this study was to evaluate the diagnostic efficiency for
      hepatocellular carcinoma (HCC) with the combined analysis of alpha-l-fucosidase
      (AFU), alpha-fetoprotein (AFP) and thymidine kinase 1 (TK1). Serum levels of AFU,
      AFP and TK1 were measured in: 116 patients with HCC, 109 patients with benign
      hepatic diseases, and 104 normal subjects. The diagnostic value was analyzed
      using the logistic regression equation and receiver operating characteristic
      curves (ROC). Statistical distribution of the three tested tumor markers in every
      group was non-normally distributed (Kolmogorov-Sminov test, Z = 0.156-0.517, P <
      0.001). The serum levels of AFP and TK1 in patients with HCC were significantly
      higher than those in patients with benign hepatic diseases (Mann-Whitney U test,
      Z = -8.570 to -5.943, all P < 0.001). However, there was no statistically
      significant difference of AFU between these two groups (Mann-Whitney U test, Z = 
      1.820, P = 0.069). The levels of AFU were significantly higher in patients with
      benign hepatic diseases than in normal subjects (Mann-Whitney U test, Z = -7.984,
      P < 0.001). Receiver operating characteristic curves (ROC) in patients with HCC
      versus those without HCC indicated the optimal cut-off value was 40.80 U/L for
      AFU, 10.86 MUg/L for AFP and 1.92 pmol/L for TK1, respectively. The area under
      ROC curve (AUC) was 0.718 for AFU, 0.832 for AFP, 0.773 for TK1 and 0.900 for the
      combination of the three tumor markers. The combination resulted in a higher
      Youden index and a sensitivity of 85.3%. The combined detection of serum AFU, AFP
      and TK1 could play a complementary role in the diagnosis of HCC, and could
      significantly improve the sensitivity for the diagnosis of HCC. 

PMID- 25870784
TI  - Novel Cosic resonance (standing wave) solutions for components of the JAK-STAT
      cellular signaling pathway: A convergence of spectral density profiles.
AB  - Cosic discovered that spectral analyses of a protein sequence after each
      constituent amino acid had been transformed into an appropriate pseudopotential
      predicted a resonant energy between interacting molecules. Several experimental
      studies have verified the predicted peak wavelength of photons within the visible
      or near-visible light band for specific molecules. Here, this concept has been
      applied to a classic signaling pathway, JAK-STAT, traditionally composed of nine
      sequential protein interactions. The weighted linear average of the spectral
      power density (SPD) profiles of each of the eight "precursor" proteins displayed
      remarkable congruence with the SPD profile of the terminal molecule (CASP-9) in
      the pathway. These results suggest that classic and complex signaling pathways in
      cells can also be expressed as combinations of resonance energies. 

PMID- 25870785
TI  - Mining disease genes using integrated protein-protein interaction and gene-gene
      co-regulation information.
AB  - In humans, despite the rapid increase in disease-associated gene discovery, a
      large proportion of disease-associated genes are still unknown. Many network
      based approaches have been used to prioritize disease genes. Many networks, such
      as the protein-protein interaction (PPI), KEGG, and gene co-expression networks,
      have been used. Expression quantitative trait loci (eQTLs) have been successfully
      applied for the determination of genes associated with several diseases. In this
      study, we constructed an eQTL-based gene-gene co-regulation network (GGCRN) and
      used it to mine for disease genes. We adopted the random walk with restart (RWR)
      algorithm to mine for genes associated with Alzheimer disease. Compared to the
      Human Protein Reference Database (HPRD) PPI network alone, the integrated HPRD
      PPI and GGCRN networks provided faster convergence and revealed new disease
      related genes. Therefore, using the RWR algorithm for integrated PPI and GGCRN is
      an effective method for disease-associated gene mining. 

PMID- 25870786
TI  - Pseudozyma aphidis fungemia after abdominal surgery: First adult case.
AB  - Pseudozyma aphidis is an environmental Basidiomycete yeast, and has been involved
      in the ten past years in rare cases of invasive infection. Pseudozyma species are
      naturally resistant to caspofungin and often present decreased susceptibility or
      resistance to fluconazole. This fungus may be difficult to recognize and
      misidentifications are reported with conventional phenotypical methods. We report
      a case of P. aphidis invasive infection in an adult with a metastatic ampulloma
      who had gone through digestive surgery. 

PMID- 25870787
TI  - Gastrointestinal cryptococcoma - Immune reconstitution inflammatory syndrome or
      cryptococcal relapse in a patient with AIDS?
AB  - The introduction of antiretroviral therapy (ART) may lead to unusual paradoxical
      and unmasking presentations of opportunistic infections. Intra-abdominal
      cryptococcosis is a rare manifestation of Cryptococcus. We present the case of an
      HIV-infected patient on ART, with a history of cryptococcal meningitis who
      presented with subacute, worsening abdominal pain during immune recovery. This
      evolved into chronic abdominal pain, with thickened bowel, and abdominal
      lymphadenopathy, while receiving empiric tuberculosis treatment. At 6-months, he
      developed intestinal perforation due to a histologically confirmed cryptococcoma.

PMID- 25870788
TI  - Acute appendicitis in acute leukemia and the potential role of decitabine in the
      critically ill patient.
AB  - Acute appendicitis in children with acute leukemia is uncommon and often
      recognized late. Immunocompromised host state coupled with the importance of
      avoiding treatment delays makes management additionally challenging. Leukemic
      infiltration of the appendix though rare must also be considered. Although
      successful conservative management has been reported, surgical intervention is
      required in most cases. We present our experience with acute appendicitis in
      children with acute leukemia and a case of complete remission of acute myeloid
      leukemia with a short course of decitabine. Decitabine may serve as bridging
      therapy in critically ill patients who are unable to undergo intensive
      chemotherapy. 

PMID- 25870789
TI  - Recurrent status epilepticus as the primary neurological manifestation of
      CADASIL: A case report.
AB  - Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy (CADASIL) often presents with a history of migraine with aura
      and eventual manifestations of dementia with unrelenting, repeated cerebral
      vascular insults. Only 6-10% of patients with CADASIL have been reported to
      develop seizures, and status epilepticus (SE) is exceedingly rare. Here, we
      describe a patient who presented with recurrent SE, with eventual biopsy
      diagnosis of CADASIL. An 80-year-old woman presented to our hospital three times
      in two years with decreased level of consciousness and subtle intermittent right
      sided upper extremity and facial twitching. There was no known significant family
      history and no past medical history for seizures, stroke, migraine headache, or
      overt dementia. Electroencephalography revealed recurrent focal seizures with
      left hemispheric onset and evolution, fulfilling the criteria for focal SE each
      time. All three admissions required sedation with midazolam to control seizure
      activity, in addition to high doses of multiple antiepileptic drugs. Brain MRI
      repeatedly showed extensive abnormalities in the periventricular and deep white
      matter, subcortical white matter, and bilateral basal ganglia. Skin biopsy was
      obtained on the third admission, and electron microscopy showed numerous deposits
      of granular osmiophilic material, which are pathognomonic for CADASIL. Detailed
      investigations failed to reveal any other etiology for the patient's condition.
      This case illustrates the potential for nonconvulsive SE to be the sole
      manifestation of CADASIL. With the appropriate brain MRI findings, CADASIL should
      be added to the list of rare causes of SE. 

PMID- 25870790
TI  - A patient with atonic seizures mimicking transient ischemic attacks.
AB  - A focal atonic seizure is a partial seizure in which the ictal manifestation
      consists of paresis of the extremities or muscles on one side of the body, and
      this phenomenon can easily be misdiagnosed as a transient ischemic attack. An 86
      year-old woman visited our hospital complaining of transient right upper
      extremity weakness lasting for 10 min following an unusual sensation in her chest
      accompanied by palpitations. On the third hospital day, she again complained of
      right arm weakness, which progressed to jerky movements of her right extremity
      accompanied by facial twitching and then generalized into a tonic-clonic seizure.
      The EEG displayed several interictal spikes in the contralateral temporal area,
      and the ictal SPECT, analyzed using the SISCOM system, showed an increased signal
      in both the contralateral superior parietal area and the mesial frontal area. In
      this case, the patient was diagnosed with focal atonic seizures as the cause of
      the monolimb weakness, which had been initially misdiagnosed aas transient
      ischemic attacks. In cases in which a patient presents with monolimb paresis,
      physicians should consider the possibility of an atonic seizure as the cause. 

PMID- 25870791
TI  - An interictal schizophrenia-like psychosis in an adult patient with 22q11.2
      deletion syndrome.
AB  - In addition to causing polymalformative syndrome, 22q11.2 deletion can lead to
      various neuropsychiatric disorders including mental retardation, psychosis, and
      epilepsy. However, few reports regarding epilepsy-related psychosis in 22q11.2
      deletion syndrome (22q11.2DS) exist. We describe the clinical characteristics and
      course of 22q11.2DS in a Japanese patient with comorbid mild mental retardation,
      childhood-onset localization-related epilepsy, and adult-onset, interictal
      schizophrenia-like psychosis. From a diagnostic viewpoint, early detection of
      impaired intellectual functioning and hyperprolinemia in patients with epilepsy
      with 22q11.2DS may be helpful in predicting the developmental timing of
      interictal psychosis. From a therapeutic viewpoint, special attention needs to be
      paid to phenytoin-induced hypocalcemia in this syndrome. 

PMID- 25870792
TI  - Preface-molecular genetics of lung cancer.

PMID- 25870793
TI  - Epidermal growth factor receptor in non-small cell lung cancer.
AB  - Following the identification of a group of patients in the initial tyrosine
      kinase inhibitor (TKI) trials for lung cancer, there has been detailed focus on
      which patients may benefit from inhibitor therapy. This article reviews the
      background, genetics and prevalence of epidermal growth factor mutations in non
      small cell lung cancer (NSCLC). Additionally, the prevalence in unselected
      patients is compared against various other reviews. 

PMID- 25870794
TI  - The suitability of small biopsy and cytology specimens for EGFR and other
      mutation testing in non-small cell lung cancer.
AB  - BACKGROUND: Patients with advanced non-small cell lung cancer (NSCLC) benefit
      from treatment with epidermal growth factor receptor (EGFR) tyrosine kinase
      inhibitors (TKIs) when their tumor harbors an activating EGFR mutation. As the
      majority of NSCLC patients present with advanced disease, cytology and small
      biopsy specimens are frequently the only tissue available for mutation testing,
      but can pose challenges due to low tumor content. We aim to better define the
      suitability of these specimens for mutation testing. METHODS: NSCLC cases
      referred to our institution for mutation testing over a 15-month period were
      retrospectively reviewed. Specimens were tested for mutations including EGFR,
      KRAS, and BRAF, using a multiplex PCR assay (OncoCarta Panel v1.0) and analyzed
      on the Agena Bioscience MassARRAY platform. RESULTS: A total of 146 specimens
      were tested, comprising 53 (36.3%) resection specimens (including 28 lung
      resection specimens), 55 (37.7%) small biopsy specimens and 38 (26%) cytology
      specimens. Of 142 cases with sufficient DNA for mutation testing, EGFR mutations
      were detected in 31 specimens (21.8%), KRAS mutations in 31 specimens (21.8%) and
      BRAF mutations in three specimens (2.1%). There was no significant difference in
      the EGFR mutation rate between lung resection (10 of 28 cases; 35.7%), small
      biopsy (9 of 53 cases; 17%), and cytology specimens (8 of 36 cases; 22.2%).
      CONCLUSIONS: Our results support the utility of small biopsy and cytology
      specimens for mutation testing. Careful evaluation of the adequacy of small
      specimens is required to minimize the risk of false negative or positive results.

PMID- 25870795
TI  - Molecular methods for somatic mutation testing in lung adenocarcinoma: EGFR and
      beyond.
AB  - Somatic mutational profiling in cancer has revolutionized the practice of
      clinical oncology. The discovery of driver mutations in non-small cell lung
      cancer (NSCLC) is an example of this. Molecular testing of lung adenocarcinoma is
      now considered standard of care and part of the diagnostic algorithm. This
      article provides an overview of the workflow of molecular testing in a clinical
      diagnostic laboratory discussing in particular novel assays that are currently in
      use for somatic mutation detection in NSCLC focussing on epidermal growth factor
      receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK), ROS1 and RET
      rearrangements. 

PMID- 25870796
TI  - BRAF mutations in non-small cell lung cancer.
AB  - BACKGROUND: BRAF is a proto-oncogene encoding a serine/threonine protein kinase
      which promotes cell proliferation and survival. BRAF mutations are commonly seen
      in melanoma and papillary thyroid carcinoma. We aimed to investigate the
      prevalence and clinicopathological features of BRAF mutations in non-small cell
      lung cancer (NSCLC) cases submitted for routine mutation testing at our
      institution. METHODS: Mutation analysis for BRAF, EGFR and KRAS was performed
      using Sequenom MassARRAY platform with OncoCarta panel v1.0. Pathological
      features were reviewed and immunohistochemistry for BRAF V600E was also
      performed. RESULTS: Seven out of 273 cases (2.6%) had BRAF mutations (three males
      and four females, median age 70 years, all smokers), with six adenocarcinomas and
      one NSCLC, not otherwise specified (NOS). All had wild-type EGFR and KRAS. The
      identified BRAF mutations were V600E (4/7, 58%), K601N, L597Q and G469V. BRAF
      V600E immunohistochemistry was positive in two cases with V600E and negative in
      one case with K601N (tissue available in three cases only). No significant
      difference in age or gender was found (BRAF mutant vs. wild-type). CONCLUSIONS:
      BRAF mutations occur in a small proportion of NSCLC that lack other driver
      mutations. The clinicopathological profile differs from that of EGFR mutant
      tumours. The potential benefits of BRAF-inhibitors should be investigated.

PMID- 25870797
TI  - Overview of clinicopathologic features of ALK-rearranged lung adenocarcinoma and
      current diagnostic testing for ALK rearrangement.
AB  - Patients with non-small cell lung cancer (NSCLC) who harbor anaplastic lymphoma
      kinase (ALK) gene rearrangements can derive significant clinical benefit from ALK
      tyrosine kinase inhibitor. Accurate patient identification is absolutely crucial
      for successful using ALK inhibitor treatment. However, lung cancer patients with
      ALK gene rearrangement after ALK inhibitor therapy eventually develop acquired
      resistance to treatment. In this review, the authors summarize the
      clinicopathologic features of ALK-rearranged NSCLC and the pros and cons of
      current diagnostic testing. In addition, we discuss the current diagnostic flow
      of ALK testing and consideration of rebiopsy sample during disease progression in
      patients treated by ALK inhibitors. 

PMID- 25870798
TI  - Beyond ALK-RET, ROS1 and other oncogene fusions in lung cancer.
AB  - Fusions of the RET and ROS1 protein tyrosine kinase oncogenes with several
      partner genes were recently identified as new targetable genetic aberrations in
      cases of non-small cell lung cancer (NSCLC) lacking activating EGFR, KRAS, ALK,
      BRAF, or HER2 oncogene aberrations. RET and ROS1 fusion-positive tumors are
      mainly observed in young, female, and/or never smoking patients. Studies based on
      in vitro and in vivo (i.e., mouse) models and studies of several fusion-positive
      patients indicate that inhibiting the kinase activity of the RET and ROS1 fusion
      proteins is a promising therapeutic strategy. Accordingly, there are several
      ongoing clinical trials aimed at examining the efficacy of tyrosine kinase
      inhibitors (TKIs) against RET and ROS1 proteins in patients with fusion-positive
      lung cancer. Other gene fusions (NTRK1, NRG1, and FGFR1/2/3) that are targetable
      by existing TKIs have also been identified in NSCLCs. Options for personalized
      lung cancer therapy will be increased with the help of multiplex diagnosis
      systems able to detect multiple druggable gene fusions. 

PMID- 25870799
TI  - Phosphatidylinositol 3-kinase-AKT-mammalian target of rapamycin (PI3K-Akt-mTOR)
      signaling pathway in non-small cell lung cancer.
AB  - Non-small cell lung cancer (NSCLC) is a devastating disease with poor prognosis.
      Systemic chemotherapy has been the mainstay of treatment in advanced disease for
      many decades. Personalized targeted therapy such as epidermal growth factor
      receptor tyrosine kinase inhibitors (EGFR TKIs) and crizotinib has significantly
      changed the treatment paradigm in NSCLC. The future success of development of
      molecular targeted therapy relies on the understanding of signal transduction
      pathways. The PI3K-Akt-mTOR pathway is commonly deregulated in human malignancy
      including NSCLC. Therefore, this pathway is a target for many therapeutic
      developments. This review will provide an overview of PI3K-Akt-mTOR signaling
      pathway, genetic alterations activating the pathway and clinical therapeutic
      development of pathway inhibitors. 

PMID- 25870802
TI  - Dr. Joshua D. Palmer: dietary intervention and future directions of cancer
      treatment.

PMID- 25870801
TI  - Adjuvant chemotherapy in non-small cell lung cancer: state-of-the-art.
AB  - Adjuvant chemotherapy (AC) plays now a significant role in the treatment of
      resected non-small cell lung cancer (NSCLC) patients and has become standard in
      clinical practice. It took more than two decades of clinical research to show its
      value, but it is has been well established that its benefit translates into a 4
      5% absolute increase in 5-year survival according to published meta-analysis.
      This improvement is obtained with two-drug, Cisplatin-based regimens (multiples
      choices are acceptable but vinorelbine is the drug with more reported evidence)
      and usually four courses are recommended. Survival increase is restricted to
      cases in which there is involvement of lymph nodes (both N1 and N2 levels). For
      N0 cases AC might be considered, with a lower level of evidence, for tumors
      larger than 4 cm in diameter. At the present time, molecular predictive factors
      and gene signatures are investigational. Patient selection is of paramount
      importance. Proper recovery from surgery and the absence of major comorbidities
      are essential features. Toxicity is significant, but manageable and transient.
      Neutropenia is the most relevant side effect due to the risk of febrile
      neutropenia. The role of timing of administration, adjuvant radiotherapy (RT) and
      of newer drugs under evaluation is also reviewed. 

PMID- 25870800
TI  - The role of the immune system in non-small cell lung carcinoma and potential for
      therapeutic intervention.
AB  - Over a hundred years after the first description of this disease, lung cancer
      represents one of the major challenges in oncology. Radical treatment cannot be
      introduced in more than 70% of cases and overall survival rate does not exceed
      15%. The immunosurveillance of lung cancer may be effective in early oncogenesis
      but is inhibited in the course of developing a clinically detectable tumor. Very
      low and heterogonous antigenicity of lung cancer cells leads to passive escape
      from anti-cancer immune defense. The cytotoxic lymphocytes (CTLs) that play a
      main role in the anticancer response are actively suppressed in the tumor
      environment and following regulatory mechanisms inhibit the recognition of tumor
      antigens by antigen presenting cells. The population of regulatory T cells
      (Tregs) is augmented and the expression of transcription factor-Foxp3 is markedly
      increased on tumor cells and tumor infiltrating lymphocytes (TIL). It is
      accomplished by M2 macrophage polarization, the activity of myeloid derived
      suppressor cells (MDSCs) and a significantly elevated concentration of cytokines:
      transforming growth factor beta (TGFbeta) and IL-10 in the tumor
      microenvironment. Very active suppression of immune protection is the predominant
      role of the programmed death 1 (PD-1)-PD-L1 pathway. The blockage of this pathway
      was found to be an effective treatment approach; therefore the monoclonal
      antibodies are being intensively investigated in lung cancer patients. Cytotoxic
      T lymphocyte antigen-4 (CTLA-4) is the molecule capable of inhibiting the
      activation signal. The antibody anti-CTLA-4 improves CTLs function in solid
      tumors and lung cancer patients may benefit from use of this agent. The second
      way in lung cancer immunotherapy is production of anti-cancer vaccines using
      recognized cancer antigens: MAGE-A3, membrane associated glycoprotein (MUC-1),
      and EGF. It was recently shown in ongoing clinical trials that combined
      therapies: immune- and chemotherapy, radiotherapy or targeted therapy seem to be
      effective. Immunotherapy in lung cancer has an individual character-there is a
      need to assess the patient's immune status prior to implementation of
      immunomodulating therapy. 

PMID- 25870803
TI  - Translational Lung Cancer Research is endorsed by the Bonnie J. Addario Lung
      Cancer Foundation.

PMID- 25870804
TI  - PD-L1 over-expression and survival in patients with non-small cell lung cancer: a
      meta-analysis.
AB  - BACKGROUND: Observational studies on the prognostic role of programmed cell death
      ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC) are controversial.
      METHODS: To clarify the impact of PD-L1 in NSCLC survival, we performed this meta
      analysis that included eligible studies. The combined hazard ratios (HR) and
      their corresponding 95% confidence intervals (CIs) were calculated in terms of
      overall survival. RESULTS: A total of five studies with 877 patients were
      evaluable for this meta-analysis. Our results suggested that PD-L1 overexpression
      had a poor impact on survival of patients with NSCLC, the HR (95% CI) was 1.43
      (1.24-1.63) overall, 1.51 (1.24-1.7954) in Asian patients, 1.35 (1.08-1.63) in
      non-Asian patients. Moreover, there was no heterogeneity between the studies.
      CONCLUSIONS: PD-L1 overexpression indicates a poor prognosis for patients with
      NSCLC.

PMID- 25870805
TI  - Sutureless aortic valve replacement: a systematic review and meta-analysis.
AB  - BACKGROUND: Sutureless aortic valve replacement (SU-AVR) has emerged as an
      innovative alternative for treatment of aortic stenosis. By avoiding the
      placement of sutures, this approach aims to reduce cross-clamp and
      cardiopulmonary bypass (CPB) duration and thereby improve surgical outcomes and
      facilitate a minimally invasive approach suitable for higher risk patients. The
      present systematic review and meta-analysis aims to assess the safety and
      efficacy of SU-AVR approach in the current literature. METHODS: Electronic
      searches were performed using six databases from their inception to January 2014.
      Relevant studies utilizing sutureless valves for aortic valve implantation were
      identified. Data were extracted and analyzed according to predefined clinical
      endpoints. RESULTS: Twelve studies were identified for inclusion of qualitative
      and quantitative analyses, all of which were observational reports. The minimally
      invasive approach was used in 40.4% of included patients, while 22.8% underwent
      concomitant coronary bypass surgery. Pooled cross-clamp and CPB duration for
      isolated AVR was 56.7 and 46.5 minutes, respectively. Pooled 30-day and 1-year
      mortality rates were 2.1% and 4.9%, respectively, while the incidences of strokes
      (1.5%), valve degenerations (0.4%) and paravalvular leaks (PVL) (3.0%) were
      acceptable. CONCLUSIONS: The evaluation of current observational evidence
      suggests that sutureless aortic valve implantation is a safe procedure associated
      with shorter cross-clamp and CPB duration, and comparable complication rates to
      the conventional approach in the short-term.

PMID- 25870806
TI  - Systematic review and meta-analysis: techniques and a guide for the academic
      surgeon.
AB  - With the rapidly growing literature across the surgical disciplines, there is a
      corresponding need to critically appraise and summarize the currently available
      evidence so they can be applied appropriately to patient care. The interpretation
      of systematic reviews is particularly challenging in cases where few robust
      clinical trials have been performed to address a particular question. However,
      risk of bias can be minimized and potentially useful conclusions can be drawn if
      strict review methodology is adhered to, including an exhaustive literature
      search, quality appraisal of primary studies, appropriate statistical
      methodology, assessment of confidence in estimates and risk of bias. Therefore,
      the following article aims to: (I) summarize to the important features of a
      thorough and rigorous systematic review or meta-analysis for the surgical
      literature; (II) highlight several underused statistical approaches which may
      yield further interesting insights compared to conventional pair-wise data
      synthesis techniques; and (III) propose a guide for thorough analysis and
      presentation of results. 

PMID- 25870807
TI  - Sutureless aortic valve replacement.
AB  - The increasing incidence of aortic stenosis and greater co-morbidities and risk
      profiles of the contemporary patient population has driven the development of
      minimally invasive aortic valve surgery and percutaneous transcatheter aortic
      valve implantation (TAVI) techniques to reduce surgical trauma. Recent
      technological developments have led to an alternative minimally invasive option
      which avoids the placement and tying of sutures, known as "sutureless" or rapid
      deployment aortic valves. Potential advantages for sutureless aortic prostheses
      include reducing cross-clamp and cardiopulmonary bypass (CPB) duration,
      facilitating minimally invasive surgery and complex cardiac interventions, whilst
      maintaining satisfactory hemodynamic outcomes and low paravalvular leak rates.
      However, given its recent developments, the majority of evidence regarding
      sutureless aortic valve replacement (SU-AVR) is limited to observational studies
      and there is a paucity of adequately-powered randomized studies. Recently, the
      International Valvular Surgery Study Group (IVSSG) has formulated to conduct the
      Sutureless Projects, set to be the largest international collaborative group to
      investigate this technology. This keynote lecture will overview the use, the
      potential advantages, the caveats, and current evidence of sutureless and rapid
      deployment aortic valve replacement (AVR). 

PMID- 25870809
TI  - Minimally invasive aortic valve surgery: Cleveland Clinic experience.
AB  - BACKGROUND: Minimally invasive surgery has become a routine approach for aortic
      valve disease over the last 18 years at the Cleveland Clinic. It is performed in
      isolation or in combination with other procedures. The objective of this study is
      to review trends and outcomes in these patients. METHODS: Cleveland Clinic
      Cardiovascular Information Registry (CVIR) was searched for aortic valve
      procedures from 1996 to 2013. All patients undergoing isolated or combined aortic
      valve operations were included for analysis. The incision type and procedure type
      were reviewed and trends were evaluated over time. Cleveland Clinic outcomes with
      minimally invasive approaches to the aortic valve are reviewed. RESULTS: A total
      of 22,766 aortic valve surgical procedures were performed in this 18-year
      timeframe. Of these, 3,385 (14.9%) were minimally invasive procedures (MIPs) and
      2,379 (10.5%) were isolated minimally invasive aortic valves. MIPs increased from
      12.4% to 29.6% of the total aortic valve volume over the period of the study.
      Combined procedures, including concomitant surgery on the aorta, mitral valve,
      tricuspid valve, and arrhythmia surgery increased over time as well. Overall
      mortality for primary and reoperative aortic valve operations continues to
      decline and has consistently been less than 1% for several years. CONCLUSIONS: A
      programmed approach to minimally invasive aortic valve surgery (MIAVS) with
      careful patient selection, appropriate use of preoperative imaging, and selective
      conversion to sternotomy when necessary, allows for aortic valve replacement
      (AVR) and a wide range of concomitant procedures to be performed safely in a
      large number of patients.

PMID- 25870810
TI  - Minimally invasive valve sparing aortic root replacement (David procedure) is
      safe.
AB  - OBJECTIVE: Even though minimally invasive cardiac surgery may reduce morbidity,
      this approach is not routinely performed for aortic root replacements. The
      purpose of this pilot study was to assess the safety and feasibility of valve
      sparing aortic root replacement via an upper mini-sternotomy up to the 3(rd)
      intercostal space. METHODS: Between April 2011 and March 2014, 26 patients (22
      males, age 47.6+/-13 years) underwent elective minimally invasive aortic valve
      sparing root replacement (David procedure, group A). Twelve patients underwent
      additional leaflet repair. Concomitant procedures were: four proximal aortic arch
      replacements and one coronary artery bypass grafting (CABG) to the proximal right
      coronary artery (RCA). During the same time period, 14 patients (ten males, age
      64.2+/-9.5 years) underwent elective David procedure via median full sternotomy
      (group B). Concomitant procedures included six proximal aortic arch replacements.
      Although the patient cohorts were small, the results of these two groups were
      compared. RESULTS: In group A, there were no intra-operative conversions to full
      sternotomy. The aortic cross-clamp and cardiopulmonary bypass (CPB) times were
      115.6+/-30.3 and 175.8+/-41.9 min, respectively. One patient was re-opened (via
      same access) due to post-operative bleeding. The post-operative ventilation time
      and hospital stay were 0.5+/-0.3 and 10.4+/-6.8 days, respectively. There was no
      30-day mortality. The patient questionnaire showed that the convalescence time
      was approximately two weeks. In group B: the cross-clamp and CPB times were
      114.1+/-19.9 and 163.0+/-24.5 min, respectively. One patient was re-opened (7.1%)
      due to post-operative bleeding. The post-operative ventilation time and hospital
      stay were 0.6+/-0.7 and 14.2+/-16.7 days, respectively. There was no 30-day
      mortality. CONCLUSIONS: Minimally invasive valve sparing aortic root replacement
      can be safely performed in selected patients. The results are comparable to those
      operated via a full sternotomy. The key to success is a 'step by step' technique
      of moving from minimally invasive aortic valve replacements (AVR) to more
      demanding aortic root replacements. Meticulous hemostasis & attention to surgical
      details is of utmost importance to prevent perioperative complications.

PMID- 25870808
TI  - Sutureless Aortic Valve Replacement International Registry (SU-AVR-IR): design
      and rationale from the International Valvular Surgery Study Group (IVSSG).
AB  - BACKGROUND: Sutureless aortic valve replacement (SU-AVR) is an innovative
      approach which shortens cardiopulmonary bypass and cross-clamp durations and may
      facilitate minimally invasive approach. Evidence outlining its safety, efficacy,
      hemodynamic profile and potential complications is replete with small-volume
      observational studies and few comparative publications. METHODS: Minimally
      invasive aortic valve surgery and high-volume SU-AVR replacement centers were
      contacted for recruitment into a global collaborative coalition dedicated to
      sutureless valve research. A Research Steering Committee was formulated to direct
      research and support the mission of providing registry evidence warranted for SU
      AVR. RESULTS: The International Valvular Surgery Study Group (IVSSG) was formed
      under the auspices of the Research Steering Committee, comprised of 36 expert
      valvular surgeons from 27 major centers across the globe. IVSSG Sutureless
      Projects currently proceeding include the Retrospective and Prospective Phases of
      the SU-AVR International Registry (SU-AVR-IR). CONCLUSIONS: The global pooling of
      data by the IVSSG Sutureless Projects will provide required robust clinical
      evidence on the safety, efficacy and hemodynamic outcomes of SU-AVR.

PMID- 25870811
TI  - Minimally invasive primary aortic valve surgery: the OLV Aalst experience.
AB  - BACKGROUND: The purpose of this study was to evaluate our in-hospital outcomes
      with primary J-sternotomy aortic valve surgery since the initiation of our
      program in 1997. METHODS: Between October 1(st) 1997 and August 31(st) 2014, 768
      patients (mean age: 69.1+/-11.2 years, 46.6% females, 15.6% aged greater than 80
      years) underwent primary JS-AVS. Additional risk factors included diabetes
      mellitus (n=98, 12.2%), peripheral vascular disease (n=42, 5.5%) and body mass
      index greater than 30 (n=144, 18.8%). The mean logistical EuroSCORE I was 5.46%+/
      4.5%. RESULTS: Aortic valve replacement and repair were performed in 758 (98.7%)
      and 10 (1.3%) patients respectively, for isolated valve stenosis (n=472, 61.8%),
      incompetence (n=56, 7.3%) and mixed valve disease (n=236, 30.9%). Valve pathology
      included sclerosis (n=516, 67.2%), rheumatic disease (n=110, 14.3%) and
      endocarditis (n=10, 1.3%). Reasons for conversion to full sternotomy (n=23, 3.0%)
      included porcelain ascending aorta (n=3, 0.4%), inadequate visualization (n=2,
      0.3%) and intra-operative complications (n=18, 2.3%). Mean length of hospital
      stay was 11.0+/-7.4 days. Morbidity included stroke (n=15, 2.0%), revision or re
      exploration (n=52, 6.8%), atrial fibrillation (n=201, 26.2%) and sternitis (n=5,
      0.7%). In-hospital mortality was 1.6% (n=12). Overall survival at 30 days was
      98.0%. CONCLUSIONS: JS-AVS is safe and is our routine approach for isolated
      aortic valve disease. Procedure related mortality is lower than predicted,
      conversion rates limited and significant morbidity minimal.

PMID- 25870812
TI  - Minimally invasive aortic valve replacement: 12-year single center experience.
AB  - BACKGROUND: This study reports the single center experience on minimally invasive
      aortic valve replacement (MIAVR), performed through a right anterior
      minithoracotomy or ministernotomy (MS). METHODS: Eight hundred and fifty-three
      patients, who underwent MIAVR from 2002 to 2014, were retrospectively analyzed.
      Survival was evaluated using the Kaplan-Meier method. The Cox multivariable
      proportional hazards regression model was developed to identify independent
      predictors of follow-up mortality. RESULTS: Median age was 73.8, and 405 (47.5%)
      of patients were female. The overall 30-day mortality was 1.9%. Four hundred and
      forty-three (51.9%) and 368 (43.1%) patients received biological and sutureless
      prostheses, respectively. Median cardiopulmonary bypass time and aortic cross
      clamping time were 108 and 75 minutes, respectively. Nineteen (2.2%) cases
      required conversion to full median sternotomy. Thirty-seven (4.3%) patients
      required re-exploration for bleeding. Perioperative stroke occurred in 15 (1.8%)
      patients, while transient ischemic attack occurred postoperative in 11 (1.3%).
      New onset atrial fibrillation was reported for 243 (28.5%) patients. After a
      median follow-up of 29.1 months (2,676.0 patient-years), survival rates at 1 and
      5 years were 96%+/-1% and 80%+/-3%, respectively. Cox multivariable analysis
      showed that advanced age, history of cardiac arrhythmia, preoperative chronic
      renal failure, MS approach, prolonged mechanical ventilation and hospital stay as
      well as wound revision were associated with higher mortality. CONCLUSIONS: MIAVR
      via both approaches is safe and feasible with excellent outcomes, and is
      associated with low conversion rate and low perioperative morbidity. Long term
      survival is at least comparable to that reported for conventional sternotomy AVR.

PMID- 25870813
TI  - Total endoscopic sutureless aortic valve replacement: rationale, development,
      perspectives.
AB  - Transcatheter valve implantation is progressively becoming the first line option
      for high risk patients in the management of severe aortic valve stenosis. Surgery
      is likely to remain the gold standard treatment option for intermediate risk
      patients since it ensures ablation of the underlying pathology and the calcified
      aortic valvular tissue, which potentially can act as a nidus of chronic
      embolization and provoke neurocognitive dysfunction in this subset of active
      patients. The surgical approach is continually evolving, with sutureless
      technology having the potential to facilitate ministernotomy and minithoracotomy
      approaches. Furthermore, Nitinol stented models can be introduced through
      thoracoscopic trocars, enabling the evolution of totally endoscopic aortic valve
      replacement (TEAVR). We present herein the development of TEAVR, starting from
      the cadaver experience in our lab. We transitioned through a clinical
      minithoracotomy video-assisted experience until we finally could initiate a
      program of human sutureless TEAVR. The limitations of this approach, which is
      still in refinement, and possible innovative solutions in order to build up a
      quick and reproducible procedure are discussed. 

PMID- 25870814
TI  - Do we need sutureless or self-anchoring aortic valve prostheses?
AB  - Surgical aortic valve replacement (AVR) is the 'gold standard' for the treatment
      of aortic valve stenosis. Due to the increasing age of the patient population
      (reflecting the demographic changes), the use of biological valves has increased
      over the past years. At the same time, a large proportion of these patients
      require concomitant surgical procedures in addition to AVR. Although trans-apical
      or trans-femoral aortic valve implantations (TAVI) have been introduced for high
      risk patients, they are limited to patients with isolated aortic valve pathology.
      Therefore, strategies for avoiding long ischemia times, as well as long periods
      of extra-corporeal circulation (ECC) resulting in reduced peri-operative risks
      should be welcomed among the surgical community. Modern 'sutureless valves' with
      reduced cross-clamp and cardio-pulmonary bypass times as a result of the absence
      of sutures, combined with excellent hemodynamics in the short and mid-term, may
      be an ideal solution for geriatric patients. Additionally, 'self-anchoring'
      valves will increase the armament of surgeons in treating 'technically difficult'
      group of patients needing AVR who have small calcified aortic roots and those
      coming back after aortic root replacement with homografts. These valves should
      also expand the application of minimally access AVR. Therefore, the question of
      whether we need 'self-anchoring valves' is not only redundant, but the time may
      have come for these type of valves to be considered as the 'valve of choice' for
      higher risk geriatric patients who may be 'high risk' for conventional valves but
      not ineligible for TAVIs. 

PMID- 25870815
TI  - From the ground up: building a minimally invasive aortic valve surgery program.
AB  - Minimally invasive aortic valve replacement (MIAVR) is associated with numerous
      advantages including improved patient satisfaction, cosmesis, decreased
      transfusion requirements, and cost-effectiveness. Despite these advantages,
      little information exists on how to build a MIAVR program from the ground up. The
      steps to build a MIAVR program include compiling a multi-disciplinary team
      composed of surgeons, cardiologists, anesthesiologists, perfusionists, operating
      room (OR) technicians, and nurses. Once assembled, this team can then approach
      hospital administrators to present a cost-benefit analysis of MIAVR, emphasizing
      the importance of reduced resource utilization in the long-term to offset the
      initial financial investment that will be required. With hospital approval,
      training can commence to provide surgeons and other staff with the necessary
      knowledge and skills in MIAVR procedures and outcomes. Marketing and advertising
      of the program through the use of social media, educational conferences, grand
      rounds, and printed media will attract the initial patients. A dedicated website
      for the program can function as a "virtual lobby" for patients wanting to learn
      more. Initially, conservative selection criteria of cases that qualify for MIAVR
      will set the program up for success by avoiding complex co-morbidities and
      surgical techniques. During the learning curve phase of the program, patient
      safety should be a priority. 

PMID- 25870816
TI  - Mini-Bentall procedure.
AB  - An important goal in cardiovascular and thoracic surgery is reducing surgical
      trauma to achieve faster recovery for our patients. Mini-Bentall procedure
      encompasses aortic root and ascending aortic replacement with re-implantation of
      coronary buttons, performed via a mini-sternotomy. The skin incision extends from
      the angle of Louis to the third intercostal space, usually measuring 5-7 cm in
      length. Through this incision, it is possible to perform isolated aortic root
      surgery and/or hemi-arch replacement. The present illustrated article describes
      the technical details on how I perform a Mini-Bentall procedure with hemi-arch
      replacement. 

PMID- 25870817
TI  - Sorin Perceval S aortic valve implantation through a mini-sternotomy approach.

PMID- 25870818
TI  - Minimally invasive rapid deployment Edwards Intuity aortic valve implantation.

PMID- 25870819
TI  - Totally endoscopic aortic valve replacement (TEAVR).

PMID- 25870820
TI  - Minimally invasive root surgery: a Bentall procedure through a J-ministernotomy.

PMID- 25870821
TI  - Medtronic 3f Enable implantation through right anterior thoracotomy.

PMID- 25870822
TI  - Minimally invasive aortic valve replacement using the Perceval S sutureless
      valve.

PMID- 25870823
TI  - Minimally invasive David reimplantation of bicuspid aortic valve.

PMID- 25870824
TI  - Mini-Bentall procedure and hemi-arch replacement.

PMID- 25870825
TI  - Aortic valve replacement with a rapid deployment Edwards Intuity bioprosthesis
      using a completely video-guided approach.

PMID- 25870826
TI  - David procedure through an upper partial sternotomy.

PMID- 25870827
TI  - In the era of the valve-in-valve: is transcatheter aortic valve implantation
      (TAVI) in sutureless valves feasible?
AB  - Sutureless aortic valve implantation has emerged as an innovative alternative for
      treatment of aortic stenosis. By avoiding the placement of sutures, this approach
      aims to improve surgical outcomes by facilitating less traumatic minimally
      invasive approaches and reducing cross-clamp and cardiopulmonary bypass duration.
      However, the absence of sutures may have detrimental effects after sutureless
      interventions, including paravalvular leakages, valve dislocation, and stent
      infolding. Transcatheter aortic valve-in-valve implantation (A-ViV) is emerging
      as a valuable procedure in patients with dysfunctioning biological aortic valves
      who are deemed inoperable with conventional surgery. Here we present the first-in
      man case of trans-femoral implant of a balloon expandable aortic valve in a
      leaking sutureless self-expandable valve. 

PMID- 25870828
TI  - Minimally invasive aortic valve replacement.

PMID- 25870829
TI  - Histone Acylation beyond Acetylation: Terra Incognita in Chromatin Biology.
AB  - Histone acetylation, one of the first and best studied histone post-translational
      modifications (PTMs), as well as the factors involved in its deposition
      (writers), binding (readers) and removal (erasers), have been shown to act at the
      heart of regulatory circuits controlling essential cellular functions. The
      identification of a variety of competing histone lysine-modifying acyl groups
      including propionyl, butyryl, 2-hydroxyisobutyryl, crotonyl, malonyl, succinyl
      and glutaryl, raises numerous questions on their functional significance, the
      molecular systems that manage their establishment, removal and interplay with the
      well-known acetylation-based mechanisms. Detailed and large-scale investigations
      of two of these new histone PTMs, crotonylation and 2-hydroxyisobutyrylation,
      along with histone acetylation, in the context of male genome programming, where
      stage-specific gene expression programs are switched on and off in turn, have
      shed light on their functional contribution to the epigenome for the first time.
      These initial investigations fired many additional questions, which remain to be
      explored. This review surveys the major results taken from these two new histone
      acylations and discusses the new biology that is emerging based on the diversity
      of histone lysine acylations. 

PMID- 25870830
TI  - The potential roles of actin in the nucleus.
AB  - Over the past few decades, actin's presence in the nucleus has been demonstrated.
      Actin is a key protein necessary for different nuclear processes. Although actin
      is well known for its functional role in dynamic behavior of the cytoskeleton,
      emerging studies are now highlighting new roles for actin. At the present time
      there is no doubt about the presence of actin in the nucleus. A number of studies
      have uncovered the functional involvement of actin in nuclear processes. Actin as
      one of the nuclear components has its own structured and functional rules, such
      as nuclear matrix association, chromatin remodeling, transcription by RNA
      polymerases I, II, III and mRNA processing. In this historical review, we attempt
      to provide an overview of our current understanding of the functions of actin in
      the nucleus. 

PMID- 25870831
TI  - The Effect of Baicalin as A PPAR Activator on Erythroid Differentiation of
      CD133(+)Hematopoietic Stem Cells in Umbilical Cord Blood.
AB  - OBJECTIVE: The peroxisome proliferator-activated receptors (PPARs) are a group of
      nu- clear receptor proteins whose functions as transcription factors regulate
      gene expres- sions. PPARs play essential roles in the regulation of cellular
      differentiation, development, and metabolism (carbohydrate, lipid, protein), and
      tumorigenesis of higher organisms. This study attempts to determine the effect of
      baicalin, a PPARgamma activator, on erythroid differentiation of cluster of
      differentiation 133(+)(CD133(+)) cord blood hematopoietic stem cells (HSCs).
      MATERIALS AND METHODS: In this experimental study, in order to investigate the
      effects of the PPARgamma agonists baicalin and troglitazone on erythropoiesis, we
      isolated CD133(+) cells from human umbilical cord blood using the MACS method.
      Isolated cells were cultured in erythroid-inducing medium with or without various
      amounts of the two PPARgamma activa- tors (baicalin and troglitazone). Erythroid
      differentiation of CD133(+)cord blood HSCs were assessed using microscopic
      morphology analysis, flow cytometric analysis of erythroid surface markers
      transferrin receptor (TfR) and glycophorin A (GPA) and bycolony forming assay.
      RESULTS: Microscopic and flow cytometric analysis revealed the erythroid
      differentiation of CD133(+)cord blood HSCs under applied erythroid inducing
      conditions. Our flow cytometric data showed that the TfR and GPA positive cell
      population diminished significantly in the presence of either troglitazone or
      baicalin. The suppression of erythroid differentiation in response to PPARgamma
      agonists was dose-dependent. Erythroid colony-forming ability of HSC decreased
      significantly after treatment with both PPARgamma agonists but troglitazone had a
      markedly greater effect. CONCLUSION: Our results have demonstrated that PPARgamma
      agonists modulate erythroid dif- ferentiation of CD133(+)HSCs, and therefore play
      an important role in regulation of normal erythropoiesis under physiologic
      conditions. Thus, considering the availability and applica- tion of this herbal
      remedy for treatment of a wide range of diseases, the inhibitory effect of
      baicalin on erythropoiesis should be noted.

PMID- 25870832
TI  - Neural differentiation of mouse bone marrow-derived mesenchymal stem cells
      treated with sex steroid hormones and basic fibroblast growth factor.
AB  - OBJECTIVE: There are several factors, like environmental agents, neurotrophic
      factors, serotonin and some hormones such as estrogen, affecting neurogenesis and
      neural differentiation. Regarding to importance of proliferation and regeneration
      in central nervous system, and a progressive increase in neurodegenerative
      diseases, cell therapy is an attractive approach in neuroscience. The aim of the
      present study was to investigate the effects of sex steroid hormones and basic
      fibroblast growth factor (bFGF) on neuronal differentiation of mouse bone marrow
      derived mesenchymal stem cells (BM-MSCs). MATERIALS AND METHODS: This
      experimental study was established in Kharazmi Univer- sity. BM was isolated from
      the bones of femur and tibia of 4-6-week old Naval Medical Research Institute
      (NMRI) mice, and the cells were cultured. The cells were divided into following 4
      groups based on the applied treatments: I. control (no treatment), II. steroid
      hormones (beta-estradiol, progesterone and testosterone), III. bFGF and IV.
      combination of steroid hormones and bFGF. Immunocytochemistry and flow cytometery
      analyses were applied for beta III-tubulin (beta-III tubulin) and microtubule
      associated proteins-2 (MAP-2) in 4 days of treatment for all groups. RESULTS: The
      cells treated with combination of bFGF and steroid hormones represented more
      expressions of neural markers as compared to control and to other two groups
      treated with either bFGF or steroid hormones. CONCLUSION: This study showed that
      BM-MSCs can express specific neural markers after receiving bFGF pretreatment
      that was followed by sex steroid hormones treatment. More investigations are
      necessary to specify whether steroid hormones and bFGF can be considered for
      treatment of CNS diseases and disorders.

PMID- 25870833
TI  - Stem cells from human exfoliated deciduous tooth exhibit stromal-derived inducing
      activity and lead to generation of neural crest cells from human embryonic stem
      cells.
AB  - OBJECTIVE: The neural crest is a transient structure of early vertebrate embryos
      that generates neural crest cells (NCCs). These cells can migrate throughout the
      body and produce a diverse array of mature tissue types. Due to the ethical and
      technical problems surrounding the isolation of these early human embryo cells,
      researchers have focused on in vitro studies to produce NCCs and increase their
      knowledge of neural crest development. MATERIALS AND METHODS: In this
      experimental study, we cultured human embryonic stem cells (hESCs) on stromal
      stem cells from human exfoliated deciduous teeth (SHED) for a two-week period. We
      used different approaches to characterize these differentiated cells as neural
      precursor cells (NPCs) and NCCs. RESULTS: In the first co-culture week, hESCs
      appeared as crater-like structures with marginal rosettes. NPCs derived from
      these structures expressed the early neural crest marker p75 in addition to
      numerous other genes associated with neural crest induction such as SNAIL, SLUG,
      PTX3 and SOX9. Flow cytometry analysis showed 70% of the cells were AP2/P75
      positive. Moreover, the cells were able to self-renew, sustain multipotent
      differentiation potential, and readily form neurospheres in suspension culture.
      CONCLUSION: SHED, as an adult stem cell with a neural crest origin, has stromal
      derived inducing activity (SDIA) and can be used as an NCC inducer from hESCs.
      These cells provide an invaluable resource to study neural crest differentiation
      in both normal and disordered human neural crest development.

PMID- 25870834
TI  - Treatment of Hypertrophic Scar in Human with Autologous Transplantation of
      Cultured Keratinocytes and Fibroblasts along with Fibrin Glue.
AB  - OBJECTIVE: Hypertrophic scar involves excessive amounts of collagen in dermal
      layer and may be painful. Nowadays, we can't be sure about effectiveness of
      procedure for hypertrophic scar management. The application of stem cells with
      natural scaffold has been the best option for treatment of burn wounds and skin
      defect, in recent decades. Fibrin glue (FG) was among the first of the natural
      biomaterials applied to enhance skin deformity in burn patients. This study aimed
      to identify an efficient, minimally invasive and economical transplantation
      procedure using novel FG from human cord blood for treatment of hypertrophic scar
      and regulation collagen synthesis. MATERIALS AND METHODS: In this case series
      study, eight patients were selected with hypertrophic scar due to full-thickness
      burns. Human keratinocytes and fibroblasts derived from adult skin donors were
      isolated and cultured. They were tested for the expression of cytokeratin 14 and
      vimentin using immunocytochemistry. FG was prepared from pooled cord blood.
      Hypertrophic scars were extensively excised then grafted by simply placing the
      sheet of FG containing autologous fibroblast and keratinocytes. Histological
      analyses were performed using Hematoxylin and eosin (H&E) and Masson's Trichrome
      (MT) staining of the biopsies after 8 weeks. RESULTS: Cultured keratinocytes
      showed a high level of cytokeratin 14 expression and also fibroblasts showed a
      high level of vimentin. Histological analyses of skin biopsies after 8 weeks of
      transplantation revealed re-epithelialization with reduction of hypertrophic
      scars in 2 patients. CONCLUSION: These results suggest may be the use of FG from
      cord blood, which is not more efficient than previous biological transporters and
      increasing hypertrophic scar relapse, but could lead to decrease pain rate.

PMID- 25870835
TI  - A bibliometric analysis of publications on pluripotent stem cell research.
AB  - OBJECTIVE: Human pluripotent stem cells are self-renewing cells with the ability
      to differentiate into a variety of cells and are viewed to have great potential
      in the field of regenerative medicine. Research in pluripotent stem cells holds
      great promise for patient specific therapy in various diseases. In this study,
      pluripotent stem cell articles published from 1991 to 2012 were screened and
      retrieved from Science Citation Index Expanded (SCI-EXPANDED). MATERIALS AND
      METHODS: In this retrospective study, the publication trend, citation trends for
      top articles, distributions of journals and Web of Science categories were
      analyzed. Five bibliometric indicators including total articles, independent
      articles, collaborative articles, first author articles, and corresponding author
      articles were applied to compare publications between countries and institutions.
      RESULTS: The impact of top articles changed from year to year. Top cited articles
      in previous publication years were not the same as recent years. "Induced
      pluripotent stem cell (s)" and "embryonic stem cell (s)" were the most used
      author keywords in pluripotent stem cell research. In addition, the winner of the
      Nobel Prize in physiology or medicine in 2012, Prof. Shinya Yamanaka, published
      four of the top ten most frequently cited articles. CONCLUSION: The comprehensive
      analysis of highly cited articles in the stem cell field could identify
      milestones and important contributors, giving a historic perspective on
      scientific progress.

PMID- 25870836
TI  - Different Methylation Patterns of RUNX2, OSX, DLX5 and BSP in Osteoblastic
      Differentiation of Mesenchymal Stem Cells.
AB  - OBJECTIVE: Runt-related transcription factor 2 (RUNX2) and osterix (OSX) as two
      specific osteoblast transcription factors and distal-less homeobox 5 (DLX5) as a
      non-specific one are of paramount importance in regulating osteoblast related
      genes including osteocalcin, bone sialoprotein (BSP), osteopontin and collagen
      type Ialpha1. The present study sets out to investigate whether epigenetic
      regulation of these genes is important in osteoblastic differentiation of
      mesenchymal stem cells (MSCs). MATERIALS AND METHODS: In this experimental study,
      MSCs were differentiated to osteoblasts under the influence of the osteogenic
      differentiation medium. DNA and RNA were extracted at days 0, 7, 14 and 21 from
      MSCs differentiating to osteoblasts. Promoter regions of RUNX2, OSX, DLX5 and BSP
      were analyzed by methylation-specific PCR (MSP). Gene expression was analyzed
      during osteoblastic differentiation by quantitative real-time polymerase chain
      reaction (PCR). RESULTS: MSP analysis revealed that promoter methylation status
      did not change in RUNX2, DLX5 and BSP during MSC osteoblastic differentiation. In
      contrast, OSX promoter showed a dynamic change in methylation pattern. Moreover,
      RUNX2, OSX, DLX5 and BSP promoter regions showed three different methylation
      patterns during MSC differentiation. Gene expression analyses confirmed these
      results. CONCLUSION: The results show that in differentiation of MSCs to
      osteoblasts, epigenetic regulation of OSX may play a leading role.

PMID- 25870837
TI  - Novel +90G>A Intronic Polymorphism of CYP2D6.
AB  - OBJECTIVE: CYP2D6, an enzyme, metabolizes a large number of commonly prescribed
      drugs. Variations in CYP2D6 gene encoding this enzyme have been associated with
      individual differences in drug metabolism rates. The purpose of our study was to
      identify some allelic variants of CYP2D6 gene and to detect defective CYP2D6
      alleles, as part of a pharmacogenetic screening program. MATERIALS AND METHODS: A
      prospective study was done on 120 participants referred to Royan Institute in
      2013. Allele and genotype frequencies for polymorphism of CYP2D6 gene in exons 1
      and 4 were determined by polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) analysis and sequencing on PCR products, respectively.
      RESULTS: We identified a novel variant of the gene encoding cytochrome P450 2D6
      (CYP2D6) at position +90 of intron 4 by sequencing method. This novel
      polymorphism of CYP2D6 has been deposited in GeneBank((r)) under the accession
      number KF225465 in Jun 2013. CONCLUSION: In the current study, we identified
      novel polymorphism in intron 4. This single nucleotide polymorphism (SNP) is
      known as +90G>A in the fourth intron.

PMID- 25870838
TI  - Association Study between Coronary Artery Disease and rs1333049 and rs10757274
      Polymorphisms at 9p21 Locus in South-West Iran.
AB  - OBJECTIVE: Coronary artery disease (CAD) is a multi-factorial and heterogenic
      disease with atherosclerosis plaques formation in internal wall of coronary
      artery. Plaque formation results to limitation of the blood reaching to
      myocardium leading to appearance of some problems, such as ischemia, sudden
      thrombosis veins and myocardial infarction (MI). Several environmental and
      genetic factors are involved in prevalence and incident of CAD as follows:
      hypertension, high low density lipoprotein-cholesterol (LDL-C), age, diabetes
      mellitus, family history of early-onset heart disease and smoking. According to
      genome wide association studies (GWAS), five polymorphisms in the 9p21 locus seem
      to be associated with the CAD. We aimed to evaluate the remarkable association of
      two polymorphisms at 9p21 locus, rs1333049 and rs10757274, with CAD. MATERIALS
      AND METHODS: This experimental study was conducted in Golestan, Aria Hospitals
      and Genetics Lab of Shahid Chamran University in the city of Ahvaz, Iran, in 2010
      2011. The collected blood samples belonging to 170 CAD patients (case group) and
      100 healthy individuals (control group) were analyzed by tetra-primer
      amplification refractory mutation system (ARMS)-polymerase chain reaction (PCR)
      technique. The results were analyzed using software package used for statistical
      analysis (SPSS; SPSS Inc., USA) version 16. A value of p<0.05 and an odd ratio
      (OR) with 95% confidence intervals (CI) were considered significant. RESULTS: The
      frequencies of CC, CG and GG genotypes for rs1333049 polymorphism in patients
      were 18.2, 65.3 and 16.5%, while in controls, the related values were 25, 67 and
      8%, respectively. GG genotypes of rs1333049 polymorphism in CAD patients were
      more than control cases (OR: 0.354, 95%CI: 0.138-0.912, p=0.032). The frequencies
      of AA, AG and GG genotypes for rs10757274 in CAD patients were 8.2, 58.3 and
      33.5%, while in controls, the related values were 35, 63 and 2%, respectively. GG
      Genotype in rs10757274 polymorphism in CAD patients was found more than control
      cases (OR: 0.014, 95% CI: 0.003 -0.065, p=0.0001). CONCLUSION: The rs1333049
      polymorphism at 9p21 locus shows a weak association with CAD, whereas rs10757274
      polymorphism reveals a significant association with CAD. These variants may help
      the identification of patients with increased risk for coronary artery disease.

PMID- 25870839
TI  - DNA damage of glioblastoma multiform cells induced by Beta radiation of iodine
      131 in the presence or absence of topotecan: a picogreen and colonogenic assay.
AB  - OBJECTIVE: Glioblastoma multiforme (GBM), one of the most common and aggressive
      malignant brain tumors, is highly resistant to radiotherapy. Numerous approaches
      have been pursued to find new radiosensitizers. We used a picogreen and
      colonogenic assay to appraise the DNA damage and cell death in a spheroid culture
      of GBM cells caused by iodine-131 (I-131) beta radiation in the presence of
      topotecan (TPT). MATERIALS AND METHODS: U87MG cells were cultured as spheroids
      with approximate diameters of 300 MUm. Cells were treated with beta radiation of
      I-131 (at a dose of 2 Gy) and/ or TPT (1 MUg/ml for 2 hours). The numbers of
      cells that survived were compared with untreated cells using a colonogenic assay.
      In addition, we evaluated possible DNA damages by the picogreen method. The
      relation between DNA damage and cell death was assessed in the experimental study
      of groups. RESULTS: The findings showed that survival fraction (SF) in the I
      131+TPT group (39%) was considerably less than the I-131 group (58.92%; p<0.05).
      The number of single strand breaks (SSB) and double strand breaks (DSB), in the
      DNA of U87MG cells treated with beta radiation of I-131 and TPT (I-131+TPT)
      significantly increased compared to cells treated with only I-131 or TPT
      (p<0.05). The amount of SSB repair was more than DSB repair (p<0.05). The
      relationship between cell death and DNA damage was close (r>=0.6) and significant
      (p<0.05) in the irradiated and treated groups. Also the maximum rate of DNA
      repair occurred 24 hours after the treatments. A significant difference was not
      observed on other days of the restoration. CONCLUSION: The findings in the
      present study indicated that TPT can sensitize U87MG cells to radiation and
      increase DNA damages. Potentially, TPT can cause an increase in damage from DSB
      and SSB by its inhibitory effects on topoisomerase enzyme and the cell cycle. The
      increased complex damages following the use of a genotoxic agent and beta I-131
      radiation, causes a significant increase the cell death because of the difficult
      repair process. By assessing the relationship between DNA damage and cell death,
      the picogreen method can be useful in predicting colonogenic assay. Consequently,
      it is suggested that co-treatment with I-131 beta radiation and TPT can improve
      GBM treatment.

PMID- 25870840
TI  - Radioprotective effect of melatonin on radiation-induced lung injury and lipid
      peroxidation in rats.
AB  - OBJECTIVE: Free radicals generated by ionizing radiation attack various cellular
      components such as lipids. The lung is a very radiosensitive organ and its damage
      is a doselimiting factor in radiotherapy treatments. Melatonin (MLT), the major
      product of the pineal gland acts as a radioprotective agent. This study aims to
      investigate the radioprotective effects of MLT on malondialdehyde (MDA) levels
      and histopathological changes in irradiated lungs. MATERIALS AND METHODS: In this
      experimental study, a total of 62 rats were divided into five groups. Group 1
      received no MLT and radiation (unT), group 2 received oral MLT (oM), group 3
      received oral MLT and their thoracic areas were irradiated with 18 Gy (oMR),
      group 4 received MLT by intraperitoneal (i.p.) injection and their thoracic areas
      were irradiated with 18 Gy (ipM-R), group 5 received only 18 Gy radiation in the
      thoracic area (R). Following radiotherapy, half of the animals in each group were
      sacrificed at 48 hours for evaluation of lipid peroxidation and early phase lung
      injuries. Other animals were sacrificed in the eighth week of the experiment for
      evaluation of the presence of late phase radiation induced lung injuries.
      RESULTS: Pre-treatment of rats with either i.p injection (p<0.05) and oral
      administration of MLT (p<0.001) significantly reduced MDA levels in red blood
      cell (RBC) samples compared to the R group. Furthermore, i.p. injection of MLT
      decreased MDA levels in plasma and tissue (p<0.05). In the early phase of lung
      injury, both administration of MLT significantly increased lymphocyte (p<0.05)
      and macrophage frequency (p<0.001). MLT reduced the lung injury index in the
      lungs compared to the R group (p<0.05). CONCLUSION: The result of this study
      confirms the radioprotective effect of MLT on lipid peroxidation, and in both
      early and late phases of radiation induced lung injuries in an animal model.

PMID- 25870841
TI  - Evaluation of mRNA Contents of YBX2 and JHDM2A Genes on Testicular Tissues of
      Azoospermic Men with Different Classes of Spermatogenesis.
AB  - OBJECTIVE: Animal model studies have shown that MSY2 and JHDM2A genes have an
      important role in spermatogenesis process and fertility of male mice. But the
      potential role of these genes in human spermatogenesis and fertility is not known
      yet. Therefore, we evaluated expression ratios of these genes in testis tissues
      of men with normal and impaired spermatogenesis. MATERIALS AND METHODS: In this
      experimental study, after RNA extraction and cDNA syn- thesis from 50 non
      obstructive azoospermic and 12 normal testis tissues, the expression ratios of
      genes were evaluated by real time polymerase chain reaction (PCR) technique.
      Hematoxcylin and eosin (H&E) staining was used for histological classification of
      testis tissues. For statistical analysis, one way analysis of variance (ANOVA)
      test was carried out. RESULTS: Our results showed a significant reduction in mRNA
      level of YBX2 in samples with impaired spermatogenesis (p<0.001) compared to
      samples with qualitatively normal spermatogenesis and normal spermatogenesis;
      however, in JHDM2A gene, despite sensible reduction in gene expression level in
      men with impaired spermatogenesis, no significant differences were shown
      (p>0.05). Furthermore in YBX2, a significant negative correlation was
      demonstrated between the efficiency score of spermatogenesis and the threshold
      cycle (CT) (r=-0.7, p<0.0001), whereas in JHDM2A, this negative correlation was
      not significant (r=-0.4, p=0.06). CONCLUSION: Generally, these data indicated
      that YBX2 and JHDM2A genes may play an important role in male infertility, and
      suggested that these molecules can act as useful biomarkers for predicting male
      infertility.

PMID- 25870842
TI  - Nitric oxide levels and total antioxidant capacity in the seminal plasma of
      infertile smoking men.
AB  - OBJECTIVE: Cigarette is a rich source of oxidants and reactive nitrogen species.
      Nitric oxide (NO) in high concentration has deleterious effects on human sperm
      function. Antioxidant defense system in seminal plasma protects spermatozoa from
      the attack of reactive oxygen metabolites. The purpose of this study was to
      determine the correlation between cigarette smoking with the NO levels and the
      total antioxidant capacity (TAC) of the seminal plasma in infertile smoker men
      and to compare severity of oxidative stress (OS) in them with fertile and
      infertile non-smoking men. MATERIALS AND METHODS: In this cross sectional study,
      a total of 95 male participants attended the Infertility Clinic of the Fatehmeh
      zahra Hospital in Babol, Mazandaran Province, Iran, between 2010 and 2011. They
      were divided into three groups: I. fertile non-smokers (F.ns; n=32), II.
      infertile non-smokers (IF.ns; n=30) and III. infertile smokers (IF.s; n=33)
      according to semen analysis World Health Organization guidelines (WHO, 2001) and
      smoking data. TAC concentration and NO levels of seminal plasma were measured
      using the ferric reducing ability of plasma (FRAP) method and the Griess reagent,
      respectively. RESULTS: Standard sperm parameters were significantly higher in the
      fertile group than those in the infertile groups, but these differences between
      the IF.ns and IF.s were not statistically significant. The mean TAC in the
      seminal plasma was higher in the F.ns>IF.ns>IF.s, respectively, but these
      differences were not statistically significant among three groups (p= 0.096). In
      contrast, the mean NO level in the seminal plasma was lower in the F.ns<IF.ns<
      IF.s, respectively. These differences were statistically significant among the
      three groups (p= 0.018). CONCLUSION: It argued that the increased NO levels
      associated with smoking might exceed the capacity of antioxidant defense system,
      leading to increased oxidative damage of seminal plasma and decreased fertility
      in men.

PMID- 25870843
TI  - Modulating Effects of Spirulina platensis against Tilmicosin-Induced
      Cardiotoxicity in Mice.
AB  - OBJECTIVE: Tilmicosin (TIL) is a long-acting macrolide antibiotic used to treat
      cattle for pathogens that cause bovine respiratory disease. However, overdoses of
      this medication have been reported to induce cardiac damage. Our experimental
      objective was to evaluate the protective effects of Spirulina platensis (SP)
      administration against TIL-induced cardiotoxicity in mice. MATERIALS AND METHODS:
      Our experimental in vivo animal study used 40 male albino mice that were divided
      into five groups of eight mice per group. The first group served as a control
      group and was injected with saline. The second group received SP at dose of 1000
      mg/kg body weight for five days. The third group received a single dose of TIL
      (75 mg/kg, subcutaneously). Groups 4 and 5 were given SP at doses of 500 and 1000
      mg/kg body weight for five consecutive days just before administration of TIL at
      the same dose and regimen used for group 3. RESULTS: TIL treated animals showed a
      significant increase in serum cardiac injury biomarkers as well as cardiac lipid
      peroxidation, however they had evidence of an inhibition in antioxidant
      biomarkers. SP normalized elevated serum levels of lactate dehydrogenase (LDH),
      creatine kinase (CK), and CK-MB. Furthermore, SP reduced TIL-induced lipid
      peroxidation and oxidative stress in a dose-dependent manner. CONCLUSION:
      Administration of SP minimized the toxic effects of TIL by its free
      radicalscavenging and potent antioxidant activity.

PMID- 25870844
TI  - Morphological study of isolated ovarian preantral follicles using fibrin gel plus
      platelet lysate after subcutaneous transplantation.
AB  - OBJECTIVE: Ovarian and follicle transplantation may preserve fertility in young
      cancer survivors. In this study, we have transplanted preantral follicles using
      fibrin gel as a carrier and fibrin gel supplemented with platelet lysate (PL) as
      a rich source of angiogenic and growth factors. The purpose of this study was to
      evaluate the role of fibrin gel and PL in follicle transplantation. MATERIALS AND
      METHODS: In this experimental study, ovaries were taken from 14-day- old Naval
      Medical Research Institute (NMRI) mice. Preantral follicles were dissected from
      the ovaries and encapsulated into fibrin gel supplemented with 5, 10, 15 or 20%
      PL, then transplanted back into the same donor mice. Fibrin gels supplemented
      with PL that contained preantral follicles were placed in a subcutaneous pocket
      in the back of the neck of the recipient, donor mouse (the same mouse that
      follicles were collected). After 14 days the grafts were processed and embedded
      in paraffin blocks, then serially sectioned for histological evaluation. We
      counted the follicles and classified them according to stage (preantral or
      antral). Data were presented as mean +/- standard error of mean (SEM) and
      analysed by analysis of variance (ANOVA) and the Kruskal-Wallistest. RESULTS: The
      mean percentage of recovered follicles encapsulated and transplanted in each
      group were 33.30 +/- 2.47 (fibrin gel), 31.96 +/- 1.90 (fibrin gel+5% PL), 34.02
      +/- 2.44 (fibrin gel+10% PL), 48.31 +/- 2.06 (fibrin gel+15% PL) and 17.60 +/-
      2.79 (fibrin gel+20% PL). There was a significant increase in the recovery rate
      of grafted follicles with fibrin gel+15% PL (48.31%; p<0.001). The percentage of
      preantral follicles showed no significant difference in all groups (p<0.05). The
      percentage of antral follicles showed a significant decrease in follicles grafted
      with fibrin gel+20% PL when compared to the other groups (11.77%; p<0.005) but no
      significant difference was observed in the other groups. CONCLUSION: The use of
      PL in follicle transplantation can improve ovarian follicular survival rate.

PMID- 25870845
TI  - Brief azacytidine step allows the conversion of suspension human fibroblasts into
      neural progenitor-like cells.
AB  - In recent years transdifferentiation technology has enabled direct conversion of
      human fibroblasts to become a valuable, abundant and accessible cell source for
      patient-specific induced cell generation in biomedical research. The majority of
      transdifferentiation approaches rely upon viral gene delivery which due to random
      integration with the host genome can cause genome instability and tumorigenesis
      upon transplantation. Here, we provide a simple way to induce neural progenitor
      like cells from human fibroblasts without genetic manipulation by changing
      physicochemical culture properties from monolayer culture into a suspension in
      the presence of a chemical DNA methyltransferase inhibitor agent, Azacytidine. We
      have demonstrated the expression of neural progenitor-like markers, morphology
      and the ability to spontaneously differentiate into neural-like cells. This
      approach is simple, inexpensive, lacks genetic manipulation and could be a
      foundation for future chemical neural transdifferentiation and a safe induction
      of neural progenitor cells from human fibroblasts for clinical applications. 

PMID- 25870846
TI  - Relationship between Salivary Alkaline Phosphatase Enzyme Activity and The
      Concentrations of Salivary Calcium and Phosphate Ions.
AB  - Although salivary alkaline phosphatase (ALP) can balance deand remineralization
      processes of enamel, there is no evidence regarding its effects on the
      concentrations of calcium and phosphate in saliva. The present study aims to
      determine the relationship between salivary ALP activity and the concentrations
      of calcium and phosphate in saliva. In this cross-sectional study, we evaluated
      salivary markers in 120 males, ages 19 to 44 years. All participants provided 5
      mL of unstimulated whole saliva and the level of enzyme activity as well as
      calcium and phosphate concentrations were measured using a colorimetric method.
      Data were gathered and analyzed by statistical package for social sciences (SPSS)
      13.00 using Pearson correlation test. A p value of <0.05 was considered
      statistically significant. The mean age of participants in the present study was
      32.95 +/- 8.09 years. The mean pH of saliva was 6.65 +/- 0.62. Salivary
      parameters included average ALP activity (5.04 +/- 1.866 U/dL), calcium (4.77 +/-
      0.877 mg/dL) and phosphate (10.38 +/- 2.301 mg/dL). Pearson correlation test
      showed no significant relationship between ALP activity and calcium and phosphate
      concentrations in saliva (p>0.05). According to the results of the present study,
      there was no significant relation between salivary ALP activity and calcium and
      phosphate concentrations in saliva. However, further research is highly
      recommended. 

PMID- 25870847
TI  - Orexin-a modulates firing of rat rostral ventromedial medulla neurons: an in
      vitro study.
AB  - The rostral ventromedial medulla (RVM) acts a key role in the descending
      inhibitory pain modulation. Neuropeptide orexin-A (ORXA) is confined to thousands
      of neurons in the lateral hypothalamus (LH). While RVM gets the orexinergic
      projections, the orexin receptors are also expressed in this structure. The aim
      of this study was to specify the cellular effects of ORXA on RVM neurons in vitro
      by using the whole cell patch-clamp recording. RVM neurons were classified into
      three types based on their electrophysiological characteristics. Type 1 neurons
      exhibited an irregular spontaneous activity which was interrupted by periods of
      pause in 25% of recorded neurons. Type 2 neurons did not show any spontaneous
      baseline activity (53.8% of recorded neurons). Type 3 neurons fired repetitively
      without interruption (51.2% of recorded neurons). ORXA had either inhibitory or
      excitatory effects on 53.8% (7/13) of type 1 neurons. ORXA excited 46.4% (13/28)
      of type 2 neurons and 27.3% (3/11) of type 3 neurons. The excitatory effect of
      ORXA observed in type 2 neurons was suppressed by an orexin 1 receptor (OXR1)
      antagonist, SB-334867. Briefly, we hypothesized that the ORXA mediated excitation
      and/or inhibition in RVM neurons might work as a mechanism to modulate pain
      processing by orexinergic neurons. 

PMID- 25870848
TI  - Reliability Evaluation of Fluorescence In Situ Hybridization (FISH) and G-Banding
      on Bone Marrow and Peripheral Blood Cells in Chronic Myelogenous Leukemia
      Patients.
AB  - Chronic myeloid leukemia (CML) is a myeloproliferative disease. The cytogenetic
      hallmark of CML is Philadelphia (Ph) chromosome. This study aimed to diagnose
      suspected CML patients, to monitor CML patients under therapy using cytogenetic
      and fluorescence in situ hybridization (FISH) techniques to analyze their bone
      marrow (BM) and peripheral blood (PB) samples, and finally to compare their
      obtained results for both specimens. This study was conducted during one-year
      period (2012-2013). The participants were recruited from the Hematology and
      Oncology Clinic of Shahid Gazi (Emam Reza) Hospital of Tabriz University of
      Medical Sciences, Tabriz, East Azerbaijan Province, Iran. We analyzed 90 samples
      from 60 suspected CML patients (30 BM and 60 PB samples). All samples were
      analyzed using G-banding, 5 samples using dual fusion FISH (DF-FISH) probes, as
      well as 30 samples using both FISH and G-banding. Among the 90 analyzed samples
      of 60 patients, 25 (41.66%) were Ph+ using karyotyping, whereas five cases were
      not analyzable, so FISH was applied and the results confirmed that only two
      individuals were BCR-ABL+. In the comparison between 25 BM and 25 PB samples
      using karyotyping, 15 (60%) and 10 (40%) were ph+, respectively. The comparison
      of FISH and karyotyping on 30 samples showed that 9 (30%) and 8 (26.66%) were
      Ph+, respectively, and only 18.18% of Ph+ patients showed atypical patterns. In
      the comparison between BM-cytogenetic and PB- interphase-FISH (I-FISH), BM
      cytogenetic was more reliable than PB-I-FISH in detecting Ph. Our data
      demonstrate that FISH analysis is a rapid, reliable and sensitive technique. The
      comparison between BM and PB showed that PB can not be replaced by BM, even in
      detecting by FISH. 

PMID- 25870849
TI  - Comparative study of the influence of EDTA and sodium heparin on long term
      storage of cattle DNA.
AB  - Blood collection in heparin tubes for cytogenetic, and ethylenediaminetetraacetic
      acid (EDTA) tubes for molecular genetics applications respectively, are routine
      practices everywhere. If blood samples are required for cytogenetics as well as
      DNA work, two samples from each animal are usually collected, which leads to
      wastage of time and money. The present study tried to explore the possibilities
      of collecting a single blood sample in a heparinised tube for use in both
      applications. Two blood samples were collected from the same animals; one in a
      heparin tube and the other in an EDTA tube. DNA was extracted and stored at the
      same temperature and for the same durations. Comparative studies revealed that
      the DNA samples extracted from blood using these two different coagulants give
      more or less the same quality of results especially for polymerase chain reaction
      (PCR) based applications in cattle. The purpose of the present study was to
      establish the possibility of using heparin blood for chromosomal studies as well
      as for molecular biology. Such a practice will obviously save time and money in
      collecting samples in duplicate. 

PMID- 25870850
TI  - P62/Ubiquitin IHC Expression Correlated with Clinicopathologic Parameters and
      Outcome in Gastrointestinal Carcinomas.
AB  - P62 and ubiquitin are small regulatory proteins demonstrated to have implications
      in the prognosis and survival of various malignancies including: hepatocellular,
      breast, ovarian, and some gastrointestinal carcinomas. Several trials studied the
      link of their activity to the extrinsic apoptosis pathway and showed that their
      autophagy modification has a critical stand point in tumorigenesis. These
      findings explain their vital role in controlling the process of cell death and
      survival. It has been shown recently that p62 and ubiquitin overexpression in
      different types of cancers, such as triple negative breast and ovarian cancers,
      have directly correlated with incidence of distant metastases. We aim to evaluate
      p62/ubiquitin expression in gastrointestinal carcinomas of gastric, colonic, and
      pancreatic origin, and correlate with annotated clinicopathologic data. In
      gastric carcinoma (61), positive p62 nuclear expression was noted in 57% and
      cytoplasmic in 61%, while positive ubiquitin was nuclear expressed in 68.8%, and
      cytoplasmic in 29.5%. In colon carcinoma (45), positive p62 nuclear expression
      was noted in 29% and cytoplasmic in 71%, while positive ubiquitin was nuclear in
      58% and cytoplasmic in 44%. In pancreatic cancer (18), positive p62 nuclear
      expression was noted in 78% and cytoplasmic in 56%, while positive ubiquitin was
      nuclear in 83% and cytoplasmic in 72%. Normal gastric (6), colon (4), and
      pancreatic (4) tissues were negative for both P62 and ubiquitin (nuclear and
      cytoplasmic staining <20%). Ubiquitin high expression was associated with more
      lymph node metastases in colon (4.14 vs 1.70, P = 0.04), and pancreatic
      adenocarcinomas (3.07 vs 0.33, P = 0.03). Also, ubiquitin high expression was
      associated with worse pancreatic adenocarcinoma overall survival (1.37 vs 2.26
      mos, P = 0.04). In addition, gastric cancer patients with high p62 expression
      tend to have more poorly differentiated grade when compared to those with low
      expression (21 vs 17, P = 0.04) but less lymph node metastases (2.77 vs 5.73, P =
      0.01). P62 and ubiquitin expression did not correlate with other
      clinicopathologic parameters in gastric, colon or pancreatic denocarcinomas. The
      results suggest that p62 and ubiquitin are highly expressed in gastric, colonic,
      and pancreatic carcinomas. High ubiquitin expression was noted to have an impact
      on number of lymph node metastases in patients with colon and pancreatic
      adenocarcinomas, but on overall survival only in patients with pancreatic
      adenocarcinoma. Also, P62 high expression is correlated with poor
      differentiation, but less lymph node metastases, in gastric carcinoma. 

PMID- 25870851
TI  - Host-adapted metabolism and its regulation in bacterial pathogens.

PMID- 25870852
TI  - BikeMaps.org: A Global Tool for Collision and Near Miss Mapping.
AB  - There are many public health benefits to cycling, such as chronic disease
      reduction and improved air quality. Real and perceived concerns about safety are
      primary barriers to new ridership. Due to limited forums for official reporting
      of cycling incidents, lack of comprehensive data is limiting our ability to study
      cycling safety and conduct surveillance. Our goal is to introduce BikeMaps.org, a
      new website developed by the authors for crowd-source mapping of cycling
      collisions and near misses. BikeMaps.org is a global mapping system that allows
      citizens to map locations of cycling incidents and report on the nature of the
      event. Attributes collected are designed for spatial modeling research on
      predictors of safety and risk, and to aid surveillance and planning. Released in
      October 2014, within 2 months the website had more than 14,000 visitors and
      mapping in 14 countries. Collisions represent 38% of reports (134/356) and near
      misses 62% (222/356). In our pilot city, Victoria, Canada, citizens mapped data
      equivalent to about 1 year of official cycling collision reports within 2 months
      via BikeMaps.org. Using report completeness as an indicator, early reports
      indicate that data are of high quality with 50% being fully attributed and
      another 10% having only one missing attribute. We are advancing this technology,
      with the development of a mobile App, improved data visualization, real-time
      altering of hazard reports, and automated open-source tools for data sharing.
      Researchers and citizens interested in utilizing the BikeMaps.org technology can
      get involved by encouraging citizen mapping in their region. 

PMID- 25870853
TI  - The association constant of 5',8-cyclo-2'-deoxyguanosine with cytidine.
AB  - The association of 5',8-cyclo-2'-deoxyguanosine (cdG), a DNA tandem lesion, with
      its complementary base cytosine has been studied by voltammetry and NMR in
      chloroform, using properly silylated derivatives of the two nucleobases for
      increasing their solubilities. Both voltammetric data and NMR titrations
      indicated that the Watson-Crick complex of cytidine with cdG is weaker than that
      with guanosine, the difference being approximately of one order of magnitude
      between the two association constants. 

PMID- 25870854
TI  - Protein disulfide isomerase expression increases in resistance arteries during
      hypertension development. Effects on Nox1 NADPH oxidase signaling.
AB  - NADPH oxidases derived reactive oxygen species (ROS) play an important role in
      vascular function and remodeling in hypertension through redox signaling
      processes. Previous studies demonstrated that protein disulfide isomerase (PDI)
      regulates Nox1 expression and ROS generation in cultured vascular smooth muscle
      cells. However, the role of PDI in conductance and resistance arteries during
      hypertension development remains unknown. The aim of the present study was to
      investigate PDI expression and NADPH oxidase dependent ROS generation during
      hypertension development. Mesenteric resistance arteries (MRA) and thoracic aorta
      were isolated from 6, 8, and 12 week-old spontaneously hypertensive (SHR) and
      Wistar rats. ROS production (dihydroethidium fluorescence), PDI (WB,
      imunofluorescence), Nox1 and NOX4 (RT-PCR) expression were evaluated. Results
      show a progressive increase in ROS generation in MRA and aorta from 8 to 12 week
      old SHR. This effect was associated with a concomitant increase in PDI and Nox1
      expression only in MRA. Therefore, suggesting a positive correlation between PDI
      and Nox1 expression during the development of hypertension in MRA. In order to
      investigate if this effect was due to an increase in arterial blood pressure, pre
      hypertensive SHR were treated with losartan (20 mg/kg/day for 30 days), an AT1
      receptor antagonist. Losartan decreased blood pressure and ROS generation in both
      vascular beds. However, only in SHR MRA losartan treatment lowered PDI and Nox1
      expression to control levels. In MRA PDI inhibition (bacitracin, 0.5 mM)
      decreased Ang II redox signaling (p-ERK 1/2). Altogether, our results suggest
      that PDI plays a role in triggering oxidative stress and vascular dysfunction in
      resistance but not in conductance arteries, increasing Nox1 expression and
      activity. Therefore, PDI could be a new player in oxidative stress and functional
      alterations in resistance arteries during the establishment of hypertension. 

PMID- 25870855
TI  - Substrate-bound protein gradients to study haptotaxis.
AB  - Cells navigate in response to inhomogeneous distributions of extracellular
      guidance cues. The cellular and molecular mechanisms underlying migration in
      response to gradients of chemical cues have been investigated for over a century.
      Following the introduction of micropipettes and more recently microfluidics for
      gradient generation, much attention and effort was devoted to study cellular
      chemotaxis, which is defined as guidance by gradients of chemical cues in
      solution. Haptotaxis, directional migration in response to gradients of substrate
      bound cues, has received comparatively less attention; however, it is
      increasingly clear that in vivo many physiologically relevant guidance proteins -
      including many secreted cues - are bound to cellular surfaces or incorporated
      into extracellular matrix and likely function via a haptotactic mechanism. Here,
      we review the history of haptotaxis. We examine the importance of the reference
      surface, the surface in contact with the cell that is not covered by the cue,
      which forms a gradient opposing the gradient of the protein cue and must be
      considered in experimental designs and interpretation of results. We review and
      compare microfluidics, contact printing, light patterning, and 3D fabrication to
      pattern substrate-bound protein gradients in vitro. The range of methods to
      create substrate-bound gradients discussed herein makes possible systematic
      analyses of haptotactic mechanisms. Furthermore, understanding the fundamental
      mechanisms underlying cell motility will inform bioengineering approaches to
      program cell navigation and recover lost function. 

PMID- 25870856
TI  - Novel Cycloheximide Derivatives Targeting the Moonlighting Protein Mip Exhibit
      Specific Antimicrobial Activity Against Legionella pneumophila.
AB  - Macrophage infectivity potentiator (Mip) and Mip-like proteins are virulence
      factors in a wide range of pathogens including Legionella pneumophila. These
      proteins belong to the FK506 binding protein (FKBP) family of peptidyl-prolyl
      cis/trans-isomerases (PPIases). In L. pneumophila, the PPIase activity of Mip is
      required for invasion of macrophages, transmigration through an in vitro lung
      epithelial barrier, and full virulence in the guinea pig infection model.
      Additionally, Mip is a moonlighting protein that binds to collagen IV in the
      extracellular matrix. Here, we describe the development and synthesis of
      cycloheximide derivatives with adamantyl moieties as novel FKBP ligands, and
      analyze their effect on the viability of L. pneumophila and other bacteria. All
      compounds efficiently inhibited PPIase activity of the prototypic human FKBP12 as
      well as Mip with IC50-values as low as 180 nM and 1.7 MUM, respectively. Five of
      these derivatives inhibited the growth of L. pneumophila at concentrations of 30
      40 MUM, but exhibited no effect on other tested bacterial species indicating a
      specific spectrum of antibacterial activity. The derivatives carrying a 3,5
      dimethyladamantan-1-[yl]acetamide substitution (MT_30.32), and a 3-ethyladamantan
      1-[yl]acetamide substitution (MT_30.51) had the strongest effects in PPIase- and
      liquid growth assays. MT_30.32 and MT_30.51 were also inhibitory in macrophage
      infection studies without being cytotoxic. Accordingly, by applying a
      combinatorial approach, we were able to generate novel, hybrid inhibitors
      consisting of cycloheximide and adamantane, two known FKBP inhibitors that
      interact with different parts of the PPIase domain, respectively. Interestingly,
      despite the proven Mip-inhibitory activity, the viability of a Mip-deficient
      strain was affected to the same degree as its wild type. Hence, we also propose
      that cycloheximide derivatives with adamantyl moieties are potent PPIase
      inhibitors with multiple targets in L. pneumophila. 

PMID- 25870858
TI  - Hepatitis e virus detection in liver tissue from patients with suspected drug
      induced liver injury.
AB  - Hepatitis E virus (HEV) infection is increasingly recognized as a cause of acute
      hepatitis in the industrialized world. We aimed to determine the frequency of
      acute HEV infection in cases of suspected drug-induced liver injury (DILI),
      mainly a diagnosis of exclusion. To this aim, formalin-fixed paraffin-embedded
      (FFPE) liver tissues of all cases routinely processed in our institute during a 2
      1/2 years period in which DILI was among the differential diagnoses (157 liver
      biopsies, 1 liver explant) were subjected to semi-nested RT-PCR for the detection
      of HEV RNA. Histopathology was re-evaluated on all cases tested positive. HEV RNA
      was detectable in 3 of 158 cases (2%) tested, comprising autochthonic as well as
      travel-related infections with genotypes 1, 3, and 4 each found once,
      respectively. Histopathologic findings comprised one case with subtotal hepatic
      necrosis and two cases of acute (cholestatic) hepatitis not distinguishable from
      acute hepatitis of other etiology. Thus, the overall frequency of acute HEV
      infection as determined by detection of HEV RNA in liver tissue is substantially
      increased in patients with suspected DILI compared to the healthy population,
      emphasizing the need to actively look for HEV infection in cases of suspected
      DILI. Molecular testing for HEV RNA in routinely processed FFPE liver tissues can
      be applied to cases with undetermined HEV status. 

PMID- 25870859
TI  - Changes in knowledge of cervical cancer following introduction of human
      papillomavirus vaccine among women at high risk for cervical cancer.
AB  - PURPOSE: To describe changes in knowledge of cervical cancer prevention, human
      papillomavirus (HPV), and HPV vaccination among women at high risk for cervical
      cancer in the first five years after introduction of HPV vaccination. METHODS: In
      2007, 2008-9, and 2011, women in a multicenter U.S. cohort study completed 44
      item self-report questionnaires assessing knowledge of cervical cancer
      prevention, HPV, and HPV vaccination. Results across time were assessed for
      individuals, and three study enrollment cohorts were compared. Knowledge scores
      were correlated with demographic variables, measures of education and attention,
      and medical factors. Associations were assessed in multivariable models. RESULTS:
      In all, 974 women completed three serial questionnaires; most were minority, low
      income, and current or former smokers. The group included 652 (67%) HIV infected
      and 322 (33%) uninfected. Summary knowledge scores (possible range 0-24)
      increased from 2007 (12.8, S.D. 5.8) to 2008-9 (13.9, S.D. 5.3, P < 0.001) and to
      2011 (14.3, S.D 5.2, P < 0.0001 vs 2007 and <0.04 vs 2008-9). Higher knowledge
      scores at first and follow-up administration of questionnaires, higher income,
      and higher education level were associated with improved knowledge score at third
      administration. Women not previously surveyed had scores similar to those of the
      longitudinal group at baseline. CONCLUSION: Substantial gaps in understanding of
      HPV and cervical cancer prevention exist despite years of health education. While
      more effective educational interventions may help, optimal cancer prevention may
      require opt-out vaccination programs that do not require nuanced understanding.

PMID- 25870857
TI  - A review of cellularization strategies for tissue engineering of whole organs.
AB  - With the advent of whole organ decellularization, extracellular matrix scaffolds
      suitable for organ engineering were generated from numerous tissues, including
      the heart, lung, liver, kidney, and pancreas, for use as alternatives to
      traditional organ transplantation. Biomedical researchers now face the challenge
      of adequately and efficiently recellularizing these organ scaffolds. Herein, an
      overview of whole organ decellularization and a thorough review of the current
      literature for whole organ recellularization are presented. The cell types,
      delivery methods, and bioreactors employed for recellularization are discussed
      along with commercial and clinical considerations, such as immunogenicity,
      biocompatibility, and Food and Drug Administartion regulation. 

PMID- 25870860
TI  - Comparison of "Word" vs. "Picture" Version of the Free and Cued Selective
      Reminding Test (FCSRT) in Older Adults.
AB  - BACKGROUND: This study examined the psychometric relationship between the Word
      and Picture versions of the Free and Cued Selective Reminding Test (FCSRT) and
      developed an equation for score conversion. METHODS: 187 participants were
      administered the FCSRT-Picture and FCSRT-Word on two visits using a randomized
      counterbalanced design. RESULTS: Participants had a mean age of 82.1 (sd=5.4) and
      mean education of 14.5 (sd=3.3) years. Mean FCSRT-Picture Free Recall score (mean
      33.0, range: 17-44) was 7.9 points higher than the Word score (mean 25.1, range:
      3-43). The Picture and Word FCSRT correlations for Free Recall and Total Recall
      were r=0.56, p<0.01 and r=0.46, p<0.01, respectively. DISCUSSION: The Picture and
      Word versions of the FCSRT were moderately associated in a sample of cognitively
      normal older adults. The score mean differences and variability between FCSRT
      Picture and FCSRT-Word indicate that their scores should not be considered
      equivalent.

PMID- 25870861
TI  - Metabolic phenotyping of the Yersinia high-pathogenicity island that regulates
      central carbon metabolism.
AB  - The high-pathogenicity island (HPI) is an important determinant of the
      pathogenicity of pathogenic Yersinia microbes. The HPI carries a cluster of
      virulence genes that chiefly account for the biosynthesis, transportation and
      regulation of a virulence-associated siderophore, yersiniabactin. This
      siderophore is also present in uropathogenic E. coli (UTI89) but not in non
      uropathogenic E. coli. We sought to perform metabolic phenotyping and to
      understand how the presence of the HPI influences central carbon metabolism,
      which remains poorly understood, by combining targeted metabolomics with a
      genetic approach. Unexpectedly, our results revealed that uropathogenic E. coli
      (UPEC) with an HPI had superior metabolic homeostasis to a non-UPEC K12 strain
      without an HPI, thereby allowing UPEC with an HPI to flexibly adapt to a variety
      of growth environments. In this study, we elucidate the unrecognized regulatory
      effects of the HPI virulence genes on central carbon metabolism, in addition to
      their roles in directing yersiniabactin. These regulatory effects may be
      implicated in differentiating UPEC from non-UPEC. 

PMID- 25870863
TI  - A new potential energy surface for the ground electronic state of the LiH2
      system, and dynamics studies on the H((2)S) + LiH(X(1)Sigma(+)) -> Li((2)S) +
      H2(X(1)Sigmag(+)) reaction.
AB  - A new global potential energy surface (PES) is obtained for the ground electronic
      state of the LiH2 system based on high-level energies. The energy points are
      calculated at the multireference configuration interaction level with aug-cc-pVXZ
      (X = Q, 5) basis sets, and these energies are extrapolated to the complete basis
      set limit. The neural network method and hierarchical construction scheme are
      applied in the fitting process and the root mean square error of the fitting
      result is very small (0.004 eV). The dissociation energies and equilibrium
      distances for LiH(X(1)Sigma(+)) and H2(X(1)Sigmag(+)) obtained from the new PES
      are in good agreement with the experimental data. On the new PES, time-dependent
      wave packet studies for the H((2)S) + LiH(X(1)Sigma(+)) -> Li((2)S) +
      H2(X(1)Sigmag(+)) reaction have been carried out. In this reaction, no threshold
      is found due to the absence of an energy barrier on the minimum energy path. The
      calculated integral cross sections are high at low collision energy and will
      decrease with the increase of the collision energy. The product molecule H2 tends
      to be forward scattering due to direct reactive collisions, which becomes more
      evident at higher collision energies. 

PMID- 25870864
TI  - Specific adhesion of membranes simultaneously supports dual heterogeneities in
      lipids and proteins.
AB  - Membrane adhesion is a vital component of many biological processes.
      Heterogeneities in lipid and protein composition are often associated with the
      adhesion site. These heterogeneities are thought to play functional roles in
      facilitating signalling. Here we experimentally examine this phenomenon using
      model membranes made of a mixture of lipids that is near a phase boundary at room
      temperature. Non-adherent model membranes are in a well-mixed, disordered-fluid
      lipid phase indicated by homogeneous distribution of a fluorescent dye that is a
      marker for the fluid-disordered (Ld) phase. We specifically adhere membranes to a
      flat substrate bilayer using biotin-avidin binding. Adhesion produces two types
      of coexisting heterogeneities: an ordered lipid phase that excludes binding
      proteins and the fluorescent membrane dye, and a disordered lipid phase that is
      enriched in both binding proteins and membrane dye compared with the non-adhered
      portion of the same membrane. Thus, a single type of adhesion interaction (biotin
      avidin binding), in an initially-homogeneous system, simultaneously stabilizes
      both ordered-phase and disordered-phase heterogeneities that are compositionally
      distinct from the non-adhered portion of the vesicle. These heterogeneities are
      long-lived and unchanged upon increased temperature. 

PMID- 25870862
TI  - Dynamics and mechanisms of DNA repair by photolyase.
AB  - Photolyases, a class of flavoproteins, use blue light to repair two types of
      ultraviolet-induced DNA damage, a cyclobutane pyrimidine dimer (CPD) and a
      pyrimidine-pyrimidone (6-4) photoproduct (6-4PP). In this perspective, we review
      the recent progress in the repair dynamics and mechanisms of both types of DNA
      restoration by photolyases. We first report the spectroscopic characterization of
      flavin in various redox states and the active-site solvation dynamics in
      photolyases. We then systematically summarize the detailed repair dynamics of
      damaged DNA by photolyases and a biomimetic system through resolving all
      elementary steps on ultrafast timescales, including multiple intermolecular
      electron- and proton-transfer reactions and bond-breaking and -making processes.
      We determined the unique electron tunneling pathways, identified the key
      functional residues and revealed the molecular origin of high repair efficiency,
      and thus elucidate the molecular mechanisms and repair photocycles at the most
      fundamental level. We finally conclude that the active sites of photolyases,
      unlike the aqueous solution for the biomimetic system, provide a unique
      electrostatic environment and local flexibility and thus a dedicated synergy for
      all elementary dynamics to maximize the repair efficiency. This repair
      photomachine is the first enzyme that the entire functional evolution is
      completely mapped out in real time. 

PMID- 25870865
TI  - Persistent stromal scar after PRK and CXL: different preoperative findings,
      similar complication.

PMID- 25870866
TI  - Commentary: A response to Lyons-Ruth (2015).

PMID- 25870867
TI  - In memoriam: William "Bill" John Hartley, OAM, RCVS, FRCVS, MVSc, FRC Path., DSc,
      FACVSc, 1922-2014.

PMID- 25870868
TI  - Introduction to 'beneficial effects of psychedelics with a special focus on
      addictions'.

PMID- 25870869
TI  - Philip D. Lawley (1927-2011).

PMID- 25870870
TI  - Preface. Coronaviruses.

PMID- 25870871
TI  - 75th anniversary of the discovery of angiotensin:  a tale of two countries.

PMID- 25870872
TI  - German Society of Cardiology criteria for establishing chest pain units.

PMID- 25870873
TI  - Primary prevention of coronary artery disease  by aspirin.

PMID- 25870874
TI  - The c-di-GMP phosphodiesterase BifA regulates  biofilm development in Pseudomonas
      putida.
AB  - We previously showed the isolation of biofilmpersistent Pseudomonas putida
      mutants that fail to undergo biofilm dispersal upon entry in stationary phase.
      Two such mutants were found to bear insertions in PP0914, encoding a GGDEF/EAL
      domain protein with high similarity to Pseudomon asaeruginosa BifA. Here we show
      the phenotypic characterization of a DeltabifA mutant in P. putida KT2442.This
      mutant displayed increased biofilm and pellicle formation, cell aggregation in
      liquid medium and decreased starvation-induced biofilm dispersal relative to the
      wild type. Unlike its P. aeruginosa counterpart, P. putida BifA did not affect
      swarming motility. The hyperadherent phenotype of the DeltabifA mutant correlates
      with a general increase in cyclic diguanylate (c-di-GMP) levels, Congo Red
      binding exopolyaccharide production and transcription of the adhesin-encoding
      lapA gene. Integrity of the EAL motif and a modified GGDEF motif (altered to
      GGDQF)were crucial for BifA activity, and c-di-GMP depletion by overexpression of
      a heterologous c-di-GMP phosphodiesterase in the DeltabifA mutant restored wild
      type biofilm dispersal and lapA expression.Our results indicate that BifA is a
      phosphodiesterase involved in the regulation of the c-di-GMP pool and required
      for the generation of the low c-di-GMP signal that triggers starvation-induced
      biofilm dispersal.

PMID- 25870875
TI  - The author responds:.

PMID- 25870876
TI  - Field trial on removal of petroleum-hydrocarbon  pollutants using a microbial
      consortium for  bioremediation and rhizoremediation.
AB  - Petroleum waste sludges are toxic and dangerous that is why environmental
      protection agencies have declared their treatment top priority. Physicochemical
      treatments are expensive and environmentally unfriendly, while alternative
      biological treatments are less costly but, in general, work at a slower pace. An
      in situ bioremediation and rhizoremediation field scale trial was performed in an
      area contaminated with oil refinery sludge under semiarid climate. The
      bioremediation and rhizoremediation treatments included the use of an artificial
      consortium made up of plant growth-promoting rhizobacteria and polycyclic
      aromatic hydrocarbon-degrading bacteria,and the combined use of the mentioned
      consortium along with pasture plants respectively. Rhizoremediation revealed that
      the development of vegetation favoured the evolution of indigenous microbiota
      with potential to remove petroleum wastes. This was inferred as the decline of
      total petroleum hydrocarbons 7 months after the biological treatment.

PMID- 25870877
TI  - Functional congruence of rhizosphere microbial  communities associated to
      leguminous tree from  Brazilian semiarid region.
AB  - Semiarid environments are characterized by the uneven spread of rain throughout
      the year. This leads to the establishment of a biota that can go through long
      periods without rain. In order to understand the dynamics of rhizosphere
      microbial communities across these contrasting seasons in Caatinga, we used the
      Ion Torrent platform to sequence the metagenome of the rhizosphere of a native
      leguminous plant (Mimosa tenuiflora). The annotation indicated that most abundant
      groups detected were the Actinobacteria and Proteobacteria, and the dominant
      functional groups were carbohydrate and protein metabolisms, and that in the wet
      season, the communities carried carbohydrate and amino acid metabolisms.The major
      differences observed between seasons were higher abundance of genes related to
      carbohydrate and amino acid metabolisms in the rainy season, indicating that the
      populations present might be better adapted to a higher abundance of organic
      matter. Besides, no clear separation of samples was detected based on their
      taxonomic composition whereas the functional composition indicates that samples
      from the rain season are more related. Altogether, our results indicate that
      there is al arge functional stability in these communities mostly due to the
      selection of features that aid the biota to endure the dry season and blossom
      during rain.

PMID- 25870878
TI  - Assembly of root-associated bacteria communities:  interactions between abiotic
      and biotic factors.
AB  - Nitrogen (N) deposition in many areas of the world is over an order of magnitude
      greater than it would be in absence of human activity. We ask how abiotic (N)and
      biotic (plant host and neighborhood) effects interact to influence root
      associated bacterial (RAB)community assembly. Using 454 pyrosequencing, we
      examined RAB communities from two dominantal pine tundra plants, Geum rossii and
      Deschampsia cespitosa, under control, N addition and D. cespitosa removal
      treatments, implemented in a factorial design. We hypothesized that host would
      have the strongest effect on RAB assembly, followed by N,then neighbor
      effects.The most dominant phyla were Proteobacteria (mostly Gammaproteobacteria),
      Actinobacteria,Bacteroidetes and Acidobacteria. We found RAB communities were
      host specific, with only 17% overlap in operational taxonomic units. Host effects
      on composition were over twice as strong as Neffects. D. cespitosa RAB diversity
      declined with N, while G. rossii RAB did not. D. cespitosa removal did not
      influence G. rossii RAB community composition, but G. rossii RAB diversity
      declined with N only when D. cespitosa was absent. We conclude that RAB of both
      hosts are sensitive to N enrichment, and RAB response to N is influenced by host
      identity and plant neighborhood.

PMID- 25870879
TI  - Unwelcome passengers.

PMID- 25870880
TI  - ECG Quiz. Diffuse ST segment elevation - a diagnostic predicament.

PMID- 25870882
TI  - Silent survivors of sexual violence in conflict and the implications for HIV
      mitigation: experiences from Eritrea.
AB  - This paper considers the impacts of sexual violence perpetrated while the
      Eritrean town of Senafe was occupied by the Ethiopian military in 2000, during
      the second Ethiopia-Eritrea war. It discusses the aftermath for the survivors,
      all women and girls belonging to the Saho ethnic group, and the responses of
      other groups in the Saho community. An attempt is made to understand the reasons
      for the failure of one intervention that sought to provide support to these
      survivors of sexual violence. The potential repercussions of community denial of
      the sexual violence are addressed. These include lack of access by survivors to
      information on HIV, testing and care; refusal to face up to the possible
      infection of survivors, their husbands and unborn children, and to the
      psychological, social and economic impacts of HIV/AIDS. 

PMID- 25870881
TI  - Toward Efficient Enzymes for the Generation of Universal Blood through Structure
      Guided Directed Evolution.
AB  - Blood transfusions are critically important in many medical procedures, but the
      presence of antigens on red blood cells (RBCs, erythrocytes) means that careful
      blood-typing must be carried out prior to transfusion to avoid adverse and
      sometimes fatal reactions following transfusion. Enzymatic removal of the
      terminal N-acetylgalactosamine or galactose of A- or B-antigens, respectively,
      yields universal O-type blood, but is inefficient. Starting with the family 98
      glycoside hydrolase from Streptococcus pneumoniae SP3-BS71 (Sp3GH98), which
      cleaves the entire terminal trisaccharide antigenic determinants of both A- and B
      antigens from some of the linkages on RBC surface glycans, through several rounds
      of evolution, we developed variants with vastly improved activity toward some of
      the linkages that are resistant to cleavage by the wild-type enzyme. The
      resulting enzyme effects more complete removal of blood group antigens from cell
      surfaces, demonstrating the potential for engineering enzymes to generate antigen
      null blood from donors of various types. 

PMID- 25870883
TI  - Understanding fatalism in HIV/AIDS protection: the individual in dialogue with
      contextual factors.
AB  - Many people remain at risk of becoming HIV-infected despite large-scale
      prevention efforts. An exploratory study was conducted to investigate the
      determinants of a fatalistic attitude towards protecting the self from HIV/AIDS.
      The study utilised the Human Sciences Research Council's national, representative
      EPOP-survey among South African adults age 18 and over (n = 2 494). Frequencies
      were calculated for all the items, and scales were compiled for perceived
      hopelessness, self-efficacy to effect change and future goals. Chi-square
      analysis was conducted between indicators of fatalism and demographic variables.
      A sequential logistic regression analysis was applied to the variables: feelings
      of hopelessness, self-efficacy, future goals and socio-demographics, as possible
      determinants of a fatalistic view about protecting one's self from HIV/AIDS.
      About 30% of the South African adult population aged 18 and over indicated such a
      fatalistic view. The results of logistic regression indicated that participants
      who reported a low level of self-efficacy to effect change, a low living
      standard, feelings of hopelessness, and unclear future goals were more likely to
      express a fatalistic attitude towards HIV/AIDS protection than others. A better
      balance is required between a focus on individual risk factors and an
      understanding of the processes through which individuals are affected by socio
      economic, cultural and political contexts. On the individual level, general
      resources for living need to be developed, while the altering of contexts and
      structures in which communities function is crucial. A person-centred development
      framework in support of health and well-being could augur well for HIV
      prevention. 

PMID- 25870884
TI  - Lover, mother or worker: women's multiple roles and the HIV/AIDS and reproductive
      health agenda in Tanzania.
AB  - International and national campaigns to prevent HIV/AIDS and efforts to promote
      reproductive health remain separate in terms of conceptualisation and
      implementation. Local negotiations around reproductive health issues similarly
      seem to lack explicit attention to HIV/AIDS. This paper argues that even in
      reproductive health clinics a gap exists between the extent of knowledge of
      HIV/AIDS and AIDS talk. There also appears to be a mismatch between collective
      knowledge of the behavioural and biomedical context of HIV/AIDS and the socio
      economic context of AIDS as a lived experience. Using an ethnographic account, I
      explore how one woman's lived experience and her knowledge of AIDS can teach us
      to take HIV/AIDS into account when theorising, promoting or providing services
      for improving African women's reproductive health. The background for this
      ethnography comes from data collected during 25 months of fieldwork at 10
      maternal and child health/family planning (MCH/FP) clinic sites in the Morogoro,
      Ruvuma and Kilimanjaro regions of Tanzania. Rehema's story shows that AIDS, like
      other diseases, is significantly linked to host-susceptibility and economic
      vulnerability. Separate and competing vertical programmes on AIDS and MCH/FP, as
      commonly encountered throughout Africa, cannot meet the needs of women in
      countries like Tanzania. Yet, we still hear most often of abstinence, anti
      retrovirals and condom use as the primary focus of HIV/AIDS prevention and
      intervention in Africa. 

PMID- 25870885
TI  - Modelling a traditional game as an agent in HIV/AIDS behaviour-change education
      and communication.
AB  - The level of HIV/AIDS awareness among the Luo of western Kenya is at its highest
      yet the epidemic continues unabated. While HIV/AIDS is locally recognised as an
      emergent deadly condition, people seem unconcerned. Deaths related to HIV/AIDS
      are often euphemistically explained in terms of tuberculosis, respiratory
      diseases, and 'thinning disease' or chira. The situation is aggravated by gender
      based cultural attitudes that are unfortunately predisposing to risk of HIV
      infection. This ethnographic study explores the potential to model cultural
      constructs such as traditional games as a means of health communication and agent
      of behaviour change. The gender undertones and implications for HIV/AIDS in the
      language of the game ajua are significant in understanding community-specific HIV
      infection risk. Modelling this traditional game as an agent in HIV/AIDS behaviour
      change education and communication allows for forging a socially and culturally
      compatible and enabling intervention mechanism. The study leads to the conclusion
      that behaviour-change education and communication in a complex cultural setting
      should be culture specific and internally derived. Significantly, cultural
      constructs like traditional games can provide 'rootedness' in terms of HIV/AIDS
      communication and intervention. 

PMID- 25870886
TI  - Prevalence of HIV infection among premarital couples in southeast Nigeria.
AB  - The Catholic Church in Nigeria offers premarital HIV screening to couples, yet
      instances of voluntary screening are rare in southeast Nigeria. This study
      examines the contribution of such tests to HIV detection, and evaluates the
      prevalence of HIV infection in southeast Nigeria among couples who are planning
      to marry. Out of 858 individuals (or 429 couples) tested for HIV, 52 individuals
      were found to be HIV-positive (overall prevalence 6.1%), and females were
      marginally more affected than males. In both sexes, prevalence was higher in
      younger age groups. Prevalence among adolescent females was 10.7%. Although no
      male adolescents were screened, prevalence for the group aged 20 to 29 years was
      6.3% for females and 10.8% for males. The prevalence estimate was slightly higher
      for rural dwellers (6.2%) than for urban residents (5.9%), but this was not
      statistically significant. We propose that screening apparently healthy
      individuals, such as couples intending to marry, and who are otherwise not
      members of a group considered at high risk for HIV infection, can serve an
      important role in HIV detection in the general population. 

PMID- 25870887
TI  - The impact of participatory and non-participatory evaluations on meeting project
      objectives.
AB  - This study investigates the value of participation on meeting a project's
      objectives by comparing the impact of participatory and non-participatory
      evaluation frameworks. We assessed HIV/AIDS projects that shared similarities in
      terms of objectives and implementation strategies, but differed in their
      evaluation strategies, in order to identify differences in the outcome of the
      projects on the beneficiaries. The study concentrated on documentary and
      interview evidence of communication-based HIV/AIDS projects. The results
      highlight that in spite of socio-demographic differences, consistent use of a
      participatory methodology created an enabling environment, in terms of
      implementation, for meeting a project's objectives (particularly improved group
      awareness, knowledge, attitude, empowerment, functioning and sustainability);
      and, in terms of evaluation, a participatory methodology better enabled the
      internalisation of those objectives, through activities such as focus group
      discussions. 

PMID- 25870888
TI  - Barriers to accessing PMTCT services in a rural area of South Africa.
AB  - Despite good intentions and commitment from providers, prevention-of-mother-to
      child-transmission of HIV (PMTCT) services can be difficult for pregnant women to
      access, despite the provision of free health services for women and children. We
      examined the introduction of PMTCT services in a very poor rural area of the
      Eastern Cape, South Africa, to assess the context's impact on the provision of
      this service. Our approach involved 13 individual in-depth interviews and 26
      focus group discussions, spread over six clinics in a single district,
      supplemented by situational observations. Our goal was to suggest how access to
      PMTCT services at the clinics may be improved. Poor roads, an underdeveloped
      transport system and poor telecommunications typify the pervasive poverty in the
      study area. Families have few resources for travel and most live a long distance
      from a clinic. Accessing emergency transport is especially difficult and
      expensive. Poor infrastructure also means that many families do not have access
      to clean water, which complicates the use of infant formula. PMTCT services had
      been recently added to several clinics that provide general services to the local
      population, but that were already understaffed and over-pressured. Since the
      PMTCT services were new, some elements of the intervention and staff training
      were delayed, thus inhibiting full implementation. New staff had not been added
      to ease accumulated pressures. Thus, socio-economic context can present a
      formidable barrier to the provision of PMTCT services. Improvement in services to
      rural areas will require creative thinking, perhaps including the use of mobile
      services and the development of community structures, such as contributions to
      community health education by traditional birth attendants and local volunteer
      groups. 

PMID- 25870889
TI  - Ethical journalism in a time of AIDS.
AB  - The media's role in fighting the AIDS pandemic has come under scrutiny due to the
      scale of the pandemic, the breadth of its impact and the accompanying stigma and
      denial. There have been calls for the mobilisation of the media in general, and
      journalists in particular, in spreading public health messages. Various studies
      have criticised the representation of the issue in the media. This paper
      addresses the question of how journalists should cover the pandemic,
      interrogating how the profession's generally accepted ethics apply in this
      situation. It considers how the imperatives of truthtelling - including fairness
      and accuracy, independence and minimising harm - apply in the context of
      reporting on HIV/AIDS. Finally, the paper presents a set of nine guidelines for
      journalistic coverage that have been accepted by the Southern African Editors
      Forum. 

PMID- 25870890
TI  - Crystal Structure, Transport, and Magnetic Properties of an Ir(6+) Compound
      Ba8Al2IrO14.
AB  - The novel iridate Ba8Al2IrO14 was prepared as single crystals by self-flux
      method, thereby providing a rare example of an all-Ir(VI) compound that can be
      synthesized under ambient pressure conditions. The preparation of all-Ir(6+)
      iridate without using traditional high-pressure techniques has to our knowledge
      previously only been reported in Nd2K2IrO7 and Sm2K2IrO7. The monoclinic crystal
      structure (space group C2/m, No.12) is stable down to 90 K and contains layers of
      IrO6 octahedra separated by Ba and AlO4 tetrahedra. The material exhibits
      insulating behavior with a narrow band gap of ~0.6 eV. The positive Seebeck
      coefficient indicates hole-like dominant charge carriers. Susceptibility
      measurement shows antiferromagnetic coupling with no order down to 2 K. 

PMID- 25870891
TI  - Is death our business? Philosophical conflicts over the end-of-life in old age
      psychiatry.
AB  - OBJECTIVES: Old age psychiatrists work with end-of-life (EOL) issues and
      encounter patient deaths, but death and dying have received limited focus in old
      age psychiatry training and research. This qualitative study explores old age
      psychiatrists' experience of and approach to working with patients at the EOL.
      METHOD: Australian old age psychiatrists were purposively sampled and interviewed
      in-depth. Data saturation was achieved after nine participant interviews.
      Verbatim transcripts were analysed for themes, which were independently verified.
      RESULTS: Two dichotomous overarching themes were identified. Death is not our
      business reflected participants' experience of working in a mental health
      framework and incorporated four themes: death should not occur in psychiatry;
      working in a psychiatric treatment model; keeping a distance from death and
      unexpected death is a negative experience. Death is our business reflected
      participants' experience of working in an aged care context and incorporated four
      themes: death is part of life; encountering the EOL through dementia care; doing
      EOL work and expected death is a positive experience. CONCLUSION: Participants
      reported conflict because of the contradictory domains in which they work. They
      were comfortable working with patients at the EOL when death was expected,
      particularly in dementia. By contrast, they struggled with death as an adverse
      outcome in circumstances influenced by mental health culture, which was
      characterised by risk management, suicide prevention and a focus on recovery.
      This study has implications for models of care underpinning old age psychiatry.
      An integrated person-centred model of care may provide a contextually appropriate
      approach for practice.

PMID- 25870892
TI  - The ethics of HIV research with people who inject drugs in Africa: a desk review.
AB  - Injecting drug use is a growing problem in Africa and a growing risk factor for
      contracting HIV in the region. It is imperative that HIV research includes
      injecting drug users so that they too are able to benefit from safe and effective
      behavioural interventions and biomedical HIV prevention and treatment products.
      This article relates a critical review of the findings of a desk review of
      previously published literature. The article examines injecting drug use in
      relation to HIV-related risk and research in Kenya, Mauritius, Nigeria, South
      Africa and Tanzania. The ethical challenges of including people who inject drugs
      in HIV research in Africa are also presented. The review found injecting drug use
      to be on the increase in all the countries reviewed. HIV-risk behaviour among
      people who inject drugs, such as needle-sharing and higher-risk sexual behaviour,
      was also found to be widespread. Furthermore, criminalisation of drug use and
      strict anti-drug laws are common in the countries reviewed, while harm-reduction
      programmes for people who inject drugs were found to be limited. The review
      identified a number of ethical challenges to the involvement of people who inject
      drugs in HIV research in Africa. This includes the illegal status and stigma
      surrounding injecting drug use, which may complicate participant recruitment,
      enrolment and retention. In addition, a lack of funding for supportive programmes
      to help injecting drug users may hinder the provision of appropriate standards of
      prevention and care and treatment for those who seroconvert. 

PMID- 25870893
TI  - Transactional sex in the fishing communities along Lake Victoria, Kenya: a
      catalyst for the spread of HIV.
AB  - The study describes the nature, context and implications of a unique form of
      transactional sexual relationships in the fishing communities along Lake Victoria
      in Kisumu County, Kenya. We conducted 12 focus group discussions and 17 key
      informant interviews among fishermen, fishmongers and fish transporters in
      Kisumu. Women fishmongers in the fishing communities commonly form relationships
      with fishermen, which are often sexual, as part of the jaboya system, wherein
      women who wish to sell fish in the market secure the rights to purchase the fish
      caught by the fishermen. Due to the nature and context of the sexual intercourse,
      sex typically occurs in a hurried manner, often without preparation or
      protection. Thus, by engaging in a web of these relationships, conducted in
      contexts that compromise their ability to practice safer sex, men and women in
      these fishing communities are at increased risk of HIV. 

PMID- 25870894
TI  - The 'Fish Trader+' model: reducing female fish traders' vulnerability to HIV.
AB  - Analysis from research and practice in Africa shows that fishing communities are
      hardly reached by HIV-related services, education, and business services, partly
      because of the efforts and costs involved and a lack of good practice in reaching
      out to these often remote areas. At the same time, fish traders, especially
      women, travel regularly to remote fishing camps to purchase fish. Although female
      fish traders may be exposed to HIV, violence and abuse in their interactions and
      relationships with fishermen, economic necessity keeps them in this trade. Good
      health among fisherfolk is a basic mainstay of productive and sustainable
      fisheries, providing food and income to fishing communities and the nation at
      large. However, these benefits are severely at risk as per-capita fish supplies
      in several African countries are declining, and fisherfolk are among the
      populations most vulnerable to HIV and AIDS. Under the regional programme
      'Fisheries and HIV/AIDS in Africa: Investing in sustainable solutions,' the
      WorldFish Center conducted a socioeconomic assessment in the Kafue Flats fishery
      in Zambia to identify factors related to HIV/AIDS vulnerability among people in
      the fishing communities, particularly female fish traders. The study identified a
      variety of factors, hence the 'Fish Trader+' model of intervention was developed
      to reduce female fish traders' vulnerability to HIV by building on their economic
      rationale through the formation of savings groups. This article outlines the
      implementation of the Fish Trader+ model in Zambia and examines its potential to
      empower female fish traders so as to reduce poverty and vulnerability to HIV in
      fishing communities. 

PMID- 25870895
TI  - The Madikwe Forum: a comprehensive partnership for supporting governance of
      Botswana's HIV and AIDS response.
AB  - There is a need for actors within the philanthropic sector to pursue
      collaborative partnerships with developing nations which could result in
      sustainable country-led responses to HIV and AIDS. There is also a need to
      evaluate the structures governing these partnerships in order to determine their
      effectiveness in strengthening national responses to HIV and AIDS. This article
      presents findings from a qualitative study of a governance structure of the
      African Comprehensive HIV/AIDS Partnerships (ACHAP), namely the Madikwe Forum.
      The investigation sought to critically reflect on the role and effectiveness of
      the Madikwe Forum in Botswana's response to HIV and AIDS and to consider the
      value of such a forum for other developing nations and partnership arrangements.
      The findings indicate that the Madikwe Forum has enabled considerable progress in
      the implementation of ACHAP-supported initiatives in Botswana. The constructive
      working relationship and close alignment between ACHAP and the Botswana
      government's objectives and priority areas were viewed as critical to this
      success. However, problems exist regarding the operation of the forum as well as
      a lack of focus on monitoring and evaluation, which requires the forum's urgent
      attention. 

PMID- 25870896
TI  - Qualitative study of the influence of antidepressants on the psychological health
      of patients on antiretroviral therapy in Uganda.
AB  - The study set out to explore how HIV-positive individuals conceptualise and
      describe depression and its manifestation in their lives, and how this may change
      over time in the context of antiretroviral therapy (ART) and antidepressant
      treatment. We conducted in-depth interviews using a semi-structured interview
      guide with 26 adult HIV-positive clients receiving ART in Uganda. We asked the
      participants to describe their depression and its impact on their general health,
      physical functioning and psychological wellbeing, as well as the influences of
      receiving ART or antidepressant treatment. Although depressive experience among
      the patients was largely described in terms of criteria in the Diagnostic and
      Statistical Manual of Mental Disorders (DSM-IV-TR), some of the symptoms used to
      describe depression, such as 'thinking too much' or worrisome thoughts, did not
      fit into the DSM-IV criteria. The participants attributed their depression to
      news of the HIV diagnosis, a fear of dying, the potential socioeconomic
      consequences of their HIV infection on their family, ART side-effects and
      continued bad health. Their subjective reports indicated that the treatment of
      depression with antidepressants had made a positive impact on their general and
      psychological health. These findings highlight the need for models of HIV care
      that integrate mental health services and promote the diagnosis and treatment of
      depression in culturally sensitive ways so as to improve the quality of life and
      health outcomes for clients. However, keeping the particular study design in
      mind, these findings should be interpreted as preliminary. 

PMID- 25870897
TI  - Housing conditions of home-based care patients in Botswana and the implications
      for HIV care.
AB  - People living with HIV or with a terminal disease face frequent health risks due
      to opportunistic infections which affect their way of life and dramatically
      increase their risk of death. Increasingly, terminally ill patients in Botswana
      are cared for at home, hence the need to understand their housing conditions.
      Despite a high volume of HIV-related studies undertaken in Botswana, little
      research has examined the relationship between patients' housing conditions and
      quality of care at home. Using existing government data from the Botswana 2001
      Population and Housing Census, we investigated the housing situation for the
      households in the national home-based care (HBC) programme. Data were available
      for 8 872 households having residents enrolled in the programme. The findings
      indicate that the majority of patients under HBC are faced with housing-related
      features that can affect their quality of care and chances of recovery. The
      largest proportion of households had six or more individuals sharing one or two
      rooms, which raises health concerns for the spread of communicable diseases. In
      rural areas, few of the HBC households had indoor piped water, proper waste
      disposal or flush toilets. The lack of basic amenities such as these creates
      problems for patients as well as for caregivers. We advocate for policy that will
      address and cater to housing as part of a comprehensive and effective HBC
      programme. Housing determines where, how and when homecare is provided for sick
      individuals; therefore, achieving healthy living environments and housing
      assistance for HBC patients must be addressed by the government. It is
      recommended that an evaluation of a patient's home should be a first step in
      their enrolment in the HBC programme. Thereafter, HIV-infected or affected
      household members should be advised and assisted to make the necessary housing
      changes to maintain quality of life or accelerate the homecare patient's
      recovery. 

PMID- 25870898
TI  - Predictors of sexual behaviour among church-going youths in Nairobi, Kenya: a
      cross-denominational study.
AB  - We surveyed church-going youths in Nairobi, Kenya, to investigate denominational
      differences in their sexual behaviour and to identify factors related to those
      differences. In comparison with youths attending mainline churches, the youths
      surveyed at Pentecostal/evangelical churches were less likely to have ever had
      sex. Furthermore, although male youths in the mainline churches were more likely
      than their female counterparts to have ever had sex, no such difference emerged
      between the male and female youths attending Pentecostal/evangelical churches.
      For youths from both types of churches, not only individual religious commitment
      (being 'born again') but also contextual religiosity (i.e. the extent of
      socialisation in their faith communities) explained the variations in their
      sexual behaviour and attitudes. Finally, the effect of denomination on one's
      intention to have sex in the next 12 months was mediated by the frequency of talk
      about spiritual issues with church confidants. 

PMID- 25870899
TI  - Barriers to initiating antiretroviral therapy during pregnancy: a qualitative
      study of women attending services in Cape Town, South Africa.
AB  - Despite the rapid expansion of antiretroviral therapy (ART) programmes, uptake of
      ART in pregnancy remains suboptimal. Little is known about the barriers to
      initiating lifelong ART in pregnancy and the challenges to postpartum retention
      in HIV care, particularly in sub-Saharan African contexts with a high burden of
      disease. In this qualitative study, 28 HIV-positive pregnant or postpartum women,
      who either had initiated ART or were eligible for ART, and 21 service providers
      were interviewed in Cape Town, South Africa, to investigate these barriers.
      Prevention of vertical transmission of HIV was often the primary motivation for
      starting treatment. Key challenges to ART initiation included late first
      presentation, denial of an HIV diagnosis, fear of disclosure, and treatment side
      effects. The women expressed difficulties in accepting a lifelong commitment to
      treatment for maternal health benefit. Pregnant women who require ART face a
      triple burden of transitioning into pregnancy, accepting the HIV diagnosis, and
      recognising the urgent requirement to start lifelong ART before delivery. Focused
      interventions are required to address the psychosocial barriers to ART uptake and
      the linkages to care for pregnant HIV-positive women. 

PMID- 25870900
TI  - Impact of lipid oxidization on biophysical properties of model cell membranes.
AB  - The oxidization of glycerophospholipids in cell membranes due to aging and
      environmental stresses may cause a variety of pathological and physiological
      consequences. A variety of oxidized phospholipid products (OxPl) are produced by
      the chemical oxidization of unsaturated hydrocarbon chains, which would
      significantly change the physicochemical properties of cell membranes. In this
      work, we constructed cell membrane models in the absence and presence of two
      stable oxidized lipid products and investigated their impact on physical
      properties of supported membranes using quartz crystal microbalance with
      dissipation (QCM-D) and high-energy X-ray reflectivity (XRR). Our experimental
      findings suggest that the lipid oxidization up to 20 mol % leads to the rupture
      of vesicles right after the adsorption. Our XRR analysis unravels the membrane
      thinning and the decrease in the lateral ordering of lipids, which can be
      explained by the decrease in the lateral packing of hydrocarbon chains. Further
      studies on mechanics of membranes incorporating oxidized lipids can be attributed
      to the decrease in the bending rigidity and the increase in the permeability. 

PMID- 25870901
TI  - Epstein-Barr Virus and Human herpes virus 6 Type A DNA Enhance IL-17 Production
      in Mice.
AB  - Several studies have shown a potential association between the Herpesviridae
      members, the Epstein-Barr virus (EBV) and Human herpes virus 6 (HHV-6), and an
      increased risk of autoimmune disease development. Because of the ability of these
      viruses to cause recurrent infections, various viral antigens, including viral
      DNA, are consistently shed. These antigens may then play a role in triggering
      autoimmune processes or contributing to autoimmune mechanisms. Therefore, this
      study examined whether the DNA of EBV or that of HHV-6A is capable of triggering
      IL-17, the autoimmune-associated cytokine, in mice. BALB/c mice were
      intraperitoneally injected with various copy numbers of either EBV or HHV-6A DNA.
      One group was injected with sterile water (the DNA solvent), and another was left
      uninjected. A mouse group that was administered DNA obtained from Staphylococcus
      epidermidis was included to ensure that any observed effects would pertain to the
      viral DNA tested. Mice were sacrificed and their sera were examined using an
      enzyme-linked immunosorbent assay for IL-17 and IL-23, as pro-autoimmune
      cytokines, IL-10, as an anti-inflammatory cytokine, and IFN-gamma, as a pro
      inflammatory cytokine, on days 3, 6, and 9 post-injection. All mouse groups
      injected with different copy numbers of EBV DNA or HHV-6A DNA displayed higher IL
      17 levels than did the group injected with water on days 3, 6, and 9 post
      injection. The highest IL-17 levels appeared to coincide with a marked increase
      in IL-23 and a decrease in IL-10 levels. Unlike the S. epidermidis DNA, which
      increased IFN-gamma levels but not IL-17 or IL-23 levels, the viral DNA tested
      increased all three mediators, indicating that triggering Th17 responses is a
      specific property of EBV and HHV-6A DNA. In conclusion, EBV and HHV-6A viral DNA
      are capable of enhancing the production of the pro-inflammatory cytokine IL-17,
      which has been shown to play a role in autoimmune diseases. 

PMID- 25870902
TI  - Editorial.

PMID- 25870903
TI  - Phenotypic, functional, and plasticity features of classical and alternatively
      activated human macrophages.
AB  - Macrophages are dynamic cells that mature under the influence of signals from the
      local microenvironment into either classically (M1) or alternatively (M2)
      activated macrophages with specific functional and phenotypic properties.
      Although the phenotypic identification of M1 and M2 macrophages is well
      established in mice, this is less clear for human macrophages. In addition, the
      persistence and reversibility of polarized human phenotypes is not well
      established. Human peripheral blood monocytes were differentiated into
      uncommitted macrophages (M0) and then polarized to M1 and M2 phenotypes using
      LPS/IFN-gamma and IL-4/IL-13, respectively. M1 and M2 were identified as
      CD64(+)CD80(+) and CD11b(+)CD209(+), respectively, by flow cytometry. Polarized
      M1 cells secreted IP-10, IFN-gamma, IL-8, TNF-alpha, IL-1beta, and RANTES,
      whereas M2 cells secreted IL-13, CCL17, and CCL18. Functionally, M2 cells were
      highly endocytic. In cytokine-deficient medium, the polarized macrophages
      reverted back to the M0 state within 12 days. If previously polarized macrophages
      were given the alternative polarizing stimulus after 6 days of resting in
      cytokine-deficient medium, a switch in polarization was seen (i.e., M1
      macrophages switched to M2 and expressed CD11b(+)CD209(+) and vice versa). In
      summary, we report phenotypic identification of human M1 and M2 macrophages,
      their functional characteristics, and their ability to be reprogrammed given the
      appropriate stimuli. 

PMID- 25870904
TI  - Experimental and Modeling Investigation of the Low-Temperature Oxidation of
      Dimethyl Ether.
AB  - The oxidation of dimethyl ether (DME) was studied using a jet-stirred reactor
      over a wide range of conditions: temperatures from 500 to 1100 K; equivalence
      ratios of 0.25, 1, and 2; residence time of 2 s; pressure of 106.7 kPa (close to
      the atmospheric pressure); and an inlet fuel mole fraction of 0.02 (with high
      dilution in helium). Reaction products were quantified using two analysis
      methods: gas chromatography and continuous wave cavity ring-down spectroscopy (cw
      CRDS). cw-CRDS enabled the quantification of formaldehyde, which is one of the
      major products from DME oxidation, as well as that of hydrogen peroxide, which is
      an important branching agent in low-temperature oxidation chemistry. Experimental
      data were compared with data computed using models from the literature with
      important deviations being observed for the reactivity at low-temperature. A new
      detailed kinetic model for the oxidation of DME was developed in this study.
      Kinetic parameters used in this model were taken from literature or calculated in
      the present work using quantum calculations. This new model enables a better
      prediction of the reactivity in the low-temperature region. Under the present JSR
      conditions, error bars on predictions were given. Simulations were also
      successfully compared with experimental flow reactor, jet-stirred reactor, shock
      tube, rapid compression machine, and flame data from literature. The kinetic
      analysis of the model enabled the highlighting of some specificities of the
      oxidation chemistry of DME: (1) the early reactivity which is observed at very
      low-temperature (e.g., compared to propane) is explained by the absence of
      inhibiting reaction of the radical directly obtained from the fuel (by H atom
      abstraction) with oxygen yielding an olefin + HO2.; (2) the low-temperature
      reactivity is driven by the relative importance of the second addition to O2
      (promoting the reactivity through branching chain) and the competitive
      decomposition reactions with an inhibiting effect. 

PMID- 25870905
TI  - Incidentally discovered diffuse large B-cell lymphoma limited to the endocervical
      mucosa in a young female patient.
AB  - Primary high-grade non-Hodgkin lymphoma of the female genital tract is extremely
      rare. Vaginal bleeding, abdominal pain or urinary complaints might be its most
      frequent symptoms. We report a 27-year-old multipara who underwent large loop
      excision of the transformation zone because of the repeated finding of a low
      grade squamous intraepithelial lesion identified during routine cancer screening.
      Incidentally, CD20-positive, primary, diffuse large B-cell lymphoma infiltrating
      the mucosa of the endocervix was also diagnosed from this specimen. The case is
      unusual because the patient had no symptoms, specific colposcopic signs or
      visible mass. R-CHOP 21 immunochemotherapy was introduced and resulted in
      complete remission without hysterectomy. The patient is without any evidence of
      disease after 49 months of follow-up. Primary cervical lymphomas are mainly
      subepithelial initially, and therefore they may be under-recognized due to the
      inefficiency of smears to diagnose such lesions. Early diagnosis and available
      targeted treatment allowed a cure in the reported example.

PMID- 25870906
TI  - Hydrophobic effect as a driving force for host-guest chemistry of a multi
      receptor Keplerate-type capsule.
AB  - The effectiveness of the interactions between various alkylammonium cations and
      the well-defined spherical Keplerate-type {Mo132} capsule has been tracked by
      (1)H DOSY NMR methodology, revealing a strong dependence on the self-diffusion
      coefficient of the cationic guests balanced between the solvated and the plugging
      situations. Analysis of the data is fully consistent with a two-site exchange
      regime involving the 20 independent {Mo9O9} receptors of the capsule.
      Furthermore, quantitative analysis allowed us to determine the stability
      constants associated with the plugging process of the pores. Surprisingly, the
      affinity of the capsule for a series of cationic guests increases continuously
      with its apolar character, as shown by the significant change of the stability
      constant from 370 to 6500 for NH4(+) and NEt4(+), respectively. Such
      observations, supported by the thermodynamic parameters, evidence that the major
      factor dictating selectivity in the trapping process is the so-called
      "hydrophobic effect". Computational studies, using molecular dynamics
      simulations, have been carried out in conjunction with the experiments. Analysis
      of the radial distribution functions g(r) reveals that NH4(+) and NMe4(+) ions
      behave differently in the vicinity of the capsule. The NH4(+) ions do not exhibit
      well-defined distributions when in close vicinity. In contrast, the NMe4(+) ions
      displayed sharp distributions related to different scenarios, such as firmly
      trapped or labile guest facing the {Mo9O9} pores. Together, these experimental
      and theoretical insights should aid in the exploitation of these giant
      polyoxometalates in solution for various applications. 

PMID- 25870907
TI  - Correction to Reduced Dielectric Screening and Enhanced Energy Transfer in Single
      and Few-Layer MoS2.

PMID- 25870908
TI  - Highly Responsive Room-Temperature Hydrogen Sensing of alpha-MoO3 Nanoribbon
      Membranes.
AB  - [001]-Oriented alpha-MoO3 nanoribbons were synthesized via hydrothermal method at
      temperature from 120 to 200  degrees C and following assembled a membrane on
      interdigital electrodes to form sensors. The sensitivity, response speed, and
      recovery speed of the sensor improve with the increasing hydrothermal
      temperature. Among them, the sample obtained at 200  degrees C exhibits a room
      temperature response time of 14.1 s toward 1000 ppm of H2. The nanoribbons also
      show good selectivity against CO, ethanol, and acetone, as well as high
      sensitivity to H2 with a concentration as low as 500 ppb. The hydrogen sensing
      behavior is dependent on the redox reaction between the H2 and chemisorbed oxygen
      species. Higher hydrothermal temperature creates larger specific surface area and
      higher Mo(5+) content, leading to increased chemisorbed oxygen species on the
      nanoribbon surface. 

PMID- 25870909
TI  - Pharmacological reduction of adult hippocampal neurogenesis modifies functional
      brain circuits in mice exposed to a cocaine conditioned place preference
      paradigm.
AB  - We investigated the role of adult hippocampal neurogenesis in cocaine-induced
      conditioned place preference (CPP) behaviour and the functional brain circuitry
      involved. Adult hippocampal neurogenesis was pharmacologically reduced with
      temozolomide (TMZ), and mice were tested for cocaine-induced CPP to study c-Fos
      expression in the hippocampus and in extrahippocampal addiction-related areas.
      Correlational and multivariate analysis revealed that, under normal conditions,
      the hippocampus showed widespread functional connectivity with other brain areas
      and strongly contributed to the functional brain module associated with CPP
      expression. However, the neurogenesis-reduced mice showed normal CPP acquisition
      but engaged an alternate brain circuit where the functional connectivity of the
      dentate gyrus was notably reduced and other areas (the medial prefrontal cortex,
      accumbens and paraventricular hypothalamic nucleus) were recruited instead of the
      hippocampus. A second experiment unveiled that mice acquiring the cocaine-induced
      CPP under neurogenesis-reduced conditions were delayed in extinguishing their
      drug-seeking behaviour. But if the inhibited neurons were generated after CPP
      acquisition, extinction was not affected but an enhanced long-term CPP retention
      was found, suggesting that some roles of the adult-born neurons may differ
      depending on whether they are generated before or after drug-contextual
      associations are established. Importantly, cocaine-induced reinstatement of CPP
      behaviour was increased in the TMZ mice, regardless of the time of neurogenesis
      inhibition. The results show that adult hippocampal neurogenesis sculpts the
      addiction-related functional brain circuits, and reduction of the adult-born
      hippocampal neurons increases cocaine seeking in the CPP model. 

PMID- 25870910
TI  - Breaking and making of olefins simultaneously using ozonolysis: application to
      the synthesis of useful building blocks and macrocyclic core of solomonamides.
AB  - A simple and practical one-pot, two-directional approach to access olefinic
      esters through simultaneous breaking and making of olefins using ozonolysis of
      alkenyl aryl selenides is disclosed. The scope of the method with a variety of
      examples is demonstrated, and the end products obtained here are useful building
      blocks. As a direct application of the present method, the macrocyclic core of
      potent anti-inflammatory natural cyclic peptides, solomonamides, is synthesized. 

PMID- 25870911
TI  - Enzyme-based microfluidic chip coupled to graphene electrodes for the detection
      of D-amino acid enantiomer-biomarkers.
AB  - An electrochemical microfluidic strategy for the separation and enantiomeric
      detection of D-methionine (D-Met) and D-leucine (D-Leu) is presented. These D
      amino acids (D-AAs) act as biomarkers involved in relevant diseases caused by
      Vibrio cholerae. On a single layout microfluidic chip (MC), highly compatible
      with extremely low biological sample consumption, the strategy allowed the
      controlled microfluidic D-AA separation and the specific reaction between D-amino
      acid oxidase (DAAO) and each D-AA biomarker avoiding the use of additives (i.e.,
      cyclodextrins) for enantiomeric separation as well as any covalent immobilization
      of the enzyme into the wall channels or on the electrode surface such as in the
      biosensor-based approaches. Hybrid polymer/graphene-based electrodes were end
      channel coupled to the microfluidic system to improve the analytical performance.
      D-Met and D-Leu were successfully detected becoming this proof-of-the-concept a
      promising principle for the development of point-of-care (POC) devices for in
      situ screening of V. cholerae related diseases.

PMID- 25870912
TI  - Controlled preferential oxidation of grain boundaries in monolayer tungsten
      disulfide for direct optical imaging.
AB  - Synthetic 2D crystal films grown by chemical vapor deposition are typically
      polycrystalline, and determining grain size within domains and continuous films
      is crucial for determining their structure. Here we show that grain boundaries in
      the 2D transition metal dichalcogenide WS2, grown by CVD, can be preferentially
      oxidized by controlled heating in air. Under our developed conditions,
      preferential degradation at the grain boundaries causes an increase in their
      physical size due to oxidation. This increase in size enables their clear and
      rapid identification using a standard optical microscope. We demonstrate that
      similar treatments in an Ar environment do no show this effect, confirming that
      oxidation is the main role in the structural change. Statistical analysis of
      grain boundary (GB) angles shows dominant mirror formation. Electrical biasing
      across the GB is shown to lead to changes at the GB and their observation under
      an optical microscope. Our approach enables high-throughput screening of as
      synthesized WS2 domains and continuous films to determine their crystallinity and
      should enable improvements in future CVD growth of these materials. 

PMID- 25870913
TI  - Therapeutic Potential of 5-HT2C Receptor Agonists for Addictive Disorders.
AB  - The neurotransmitter 5-hydroxytryptamine (5-HT; serotonin) has long been
      associated with the control of a variety of motivated behaviors, including
      feeding. Much of the evidence linking 5-HT and feeding behavior was obtained from
      studies of the effects of the 5-HT releaser (dex)fenfluramine in laboratory
      animals and humans. Recently, the selective 5-HT2C receptor agonist lorcaserin
      received FDA approval for the treatment of obesity. This review examines evidence
      to support the use of selective 5-HT2C receptor agonists as treatments for
      conditions beyond obesity, including substance abuse (particularly nicotine,
      psychostimulant, and alcohol dependence), obsessive compulsive, and excessive
      gambling disorder. Following a brief survey of the early literature supporting a
      role for 5-HT in modulating food and drug reinforcement, we propose that
      intrinsic differences between SSRI and serotonin releasers may have
      underestimated the value of serotonin-based pharmacotherapeutics to treat
      clinical forms of addictive behavior beyond obesity. We then highlight the
      critical involvement of the 5-HT2C receptor in mediating the effect of
      (dex)fenfluramine on feeding and body weight gain and the evidence that 5-HT2C
      receptor agonists reduce measures of drug reward and impulsivity. A recent report
      of lorcaserin efficacy in a smoking cessation trial further strengthens the idea
      that 5-HT2C receptor agonists may have potential as a treatment for addiction.
      This review was prepared as a contribution to the proceedings of the 11th
      International Society for Serotonin Research Meeting held in Hermanus, South
      Africa, July 9-12, 2014. 

PMID- 25870914
TI  - Do supermarkets contribute to the obesity pandemic in developing countries?
AB  - OBJECTIVE: Many developing countries are undergoing a nutrition transition with
      rising rates of overweight and obesity. This nutrition transition coincides with
      a rapid expansion of supermarkets. The objective of the present research is to
      study whether supermarkets directly contribute to overweight and other changes in
      nutritional status. DESIGN: This research builds on cross-sectional observational
      data. Household- and individual-level data were collected in Kenya using a quasi
      experimental survey design. Instrumental variable regressions were employed to
      analyse the impact of supermarket purchase on nutritional status. Causal chain
      models were estimated to examine pathways through which supermarkets affect
      nutrition. SETTING: Small towns in Central Province of Kenya with and without
      supermarkets. SUBJECTS: A total of 615 adults and 216 children and adolescents.
      RESULTS: Controlling for other factors, buying in a supermarket is associated
      with a significantly higher BMI (P=0.018) and a higher probability of overweight
      (P=0.057) among adults. This effect is not observed for children and adolescents.
      Instead, buying in a supermarket seems to reduce child undernutrition measured by
      height-for-age Z-score (P=0.017). Impacts of supermarkets depend on many factors
      including people's initial nutritional status. For both adults and children, the
      nutrition effects occur through higher food energy consumption and changes in
      dietary composition. CONCLUSIONS: Supermarkets and their food sales strategies
      contribute to changing food consumption habits and nutritional outcomes. Yet the
      types of outcomes differ by age cohort and initial nutritional status. Simple
      conclusions on whether supermarkets are good or bad for nutrition and public
      health are not justified.

PMID- 25870915
TI  - Betalain induction by l-DOPA application confers photoprotection to saline
      exposed leaves of Disphyma australe.
AB  - The capacity to synthesize betalains has arisen in diverse phylogenetic lineages
      across the Caryophyllales, and because betalainic plants often grow in deserts,
      sand dunes, or salt marshes, it is likely that these pigments confer adaptive
      advantages. However, possible functional roles of foliar betalains remain largely
      unexplored and are difficult to test experimentally. We adopted a novel approach
      to examine putative photoprotective roles of betalains in leaves for which
      chloroplast function has been compromised by salinity. Responses of l-DOPA
      treated red shoots of Disphyma australe to high light and salinity were compared
      with those of naturally red- and green-leafed morphs. Betalain content and
      tyrosinase activity were measured, and Chl fluorescence profiles and H2 O2
      production were compared under white, red or green light. Green leaves lacked
      tyrosinase activity, but when supplied with exogenous l-DOPA they produced five
      betacyanins. Both the naturally red and l-DOPA-induced red leaves generated less
      H2 O2 and showed smaller declines in photosystem II quantum efficiency than did
      green leaves when exposed to white or green light, although not when exposed to
      red light. Light screening by epidermal betalains effectively reduces the
      propensity for photoinhibition and photo-oxidative stress in subjacent
      chlorenchyma. This may assist plant survival in exposed and saline environments. 

PMID- 25870916
TI  - Clinical and pathological characterization of endometrial cancer in young women:
      identification of a cohort without classical risk factors.
AB  - OBJECTIVE: Endometrial cancer (EC) is the most common gynecologic malignancy with
      known risk factors including excess estrogen and hereditary syndromes. The
      objective of this study was to determine the proportion of young women with EC
      that could be attributed to these factors and if, as we suspected, there is a
      third population of young women in which neither factor is identifiable. We were
      interested in comparing clinicopathologic characteristics and outcomes across
      subgroups in order to better inform treatment recommendations. METHODS: We
      performed a retrospective chart review of women age 15-49 diagnosed with EC or
      complex atypical hyperplasia. Demographic, clinicopathologic, treatment,
      fertility, and outcome parameters were analyzed. RESULTS: Of 719 women
      identified, 327 were fully evaluable. 57.5% fit the "High Estrogen" risk
      criteria. 8.25% met criteria for suspected Lynch syndrome. 34.25% classified as
      "Neither" had no classical risk factors identified. There were no statistical
      differences in age, gravidity, tumor grade, treatment selection and response to
      hormonal therapy. Age of menarche, stage, histology, and synchronous ovarian
      cancer differed significantly. Prevalence of synchronous ovarian cancer was 21.0%
      of "Neither", 23.1% of "Lynch", and 6.6% of "High Estrogen". For women who
      attempted pregnancy, 2/27 of "High Estrogen", 0/3 of "Lynch", and 2/16 of
      "Neither" achieved a live birth. CONCLUSIONS: This study confirmed that a third
      population of young women with EC exist that lack classical risk factors and have
      distinct clinicopathologic parameters. No difference in success of conservative
      treatment or live births was noted in the small cohort in whom this treatment
      approach was attempted.

PMID- 25870917
TI  - Comparing indocyanine green, technetium, and blue dye for sentinel lymph node
      mapping in endometrial cancer.
AB  - BACKGROUND AND AIMS: With the debate over extent of lymphadenectomy in
      endometrial cancer, sentinel lymph node (SLN) mapping may provide a focused
      approach to evaluate the most relevant lymph nodes (LN) while minimizing the
      complications. We evaluated SLN mapping using filtered technetium(99),
      indocyanine green (ICG), and blue dye. METHODS: Prospective evaluation of 100
      patients who underwent SLN mapping by using submucosal and deep stromal cervical
      injections of technetium(99), ICG, and blue dye as part of the staging for
      endometrial cancer. RESULTS: 286 SLNs were mapped (2.9 per patient) in 92% of
      patients. The bilateral detection rate was 76%. ICG had a significantly higher
      SLN detection rate than blue dye in both overall (87% vs 71%, respectively;
      p=0.005) and bilateral (65% vs 43%, respectively; p=0.002) detection, but similar
      SLN detection rates compared to technetium(99) in both overall (87% vs 88%,
      respectively; p=0.83) and bilateral (65% vs 71%, respectively; p=0.36) detection.
      In eight cases, the SLN was in the para-aortic area and in 14 cases in the pre
      sacral, hypogastric vein, or parametrial area. In nine cases, the SLN was
      positive for metastasis, and in seven cases the SLN was the only positive node.
      One SLN was falsely negative. No complications or anaphylactic reactions
      occurred. CONCLUSION: Intra-operative SLN mapping using cervical injection is
      feasible in patients with endometrial cancer and yields adequate detection rates.
      It allows mapping of SLNs in areas (pre-sacral, hypogastric vein, parametrial)
      not routinely sampled. Given the poorer performance of blue dye, surgeons may
      omit its use if a combination of ICG and technetium(99) is used.

PMID- 25870919
TI  - Coronary angiography and bronchoscopy on brain-dead donors: is informed consent
      required?

PMID- 25870918
TI  - Impact of obesity on chemotherapy management and outcomes in women with
      gynecologic malignancies.
AB  - OBJECTIVE: To describe the effects of obesity on the pharmacokinetics and dosing
      of chemotherapies and provide recommendations for chemotherapy management in
      obese women with gynecologic malignancies. METHODS: PubMEd and MEDLINE databases
      were searched for articles published before June 2014. Only English-language
      articles were considered. 84 manuscripts were reviewed and 66 were included.
      Search terms included: obesity, overweight, body mass index, body surface area,
      glomerular filtration rate, chemotherapy, ovarian cancer, endometrial cancer,
      inflammation, and pharmacokinetics, RESULTS: Obese cancer patients have worse
      clinical outcomes, compared with non-obese patients. This may be because of
      differences in pharmacokinetics, metabolic dysregulation, or physicians'
      decisions to reduce chemotherapy dose-intensity during treatment to minimize
      toxicities. A 2012 American Society of Clinical Oncology Clinical Practice
      Guideline recommends using actual body weight for chemotherapy dosing in all
      patients treated with curative intent, irrespective of obesity, to avoid
      compromising clinical outcomes, including progression free survival (PFS) and
      overall survival (OS). In women with gynecologic cancers most studies demonstrate
      no difference in PFS or OS when obese patients receive the same chemotherapy dose
      intensity as non-obese patients, except perhaps with bevacizumab. CONCLUSIONS:
      Chemotherapy dose-intensity is a critical determinant of cancer outcomes and
      should be maintained in all patients, irrespective of obesity. Future studies
      should prospectively examine the impact of obesity on clinical outcomes (adverse
      events, survival) to improve the care of this growing population of patients who
      are at risk for inferior clinical outcomes.

PMID- 25870920
TI  - Controlled synthesis of layered double hydroxide nanoplates driven by screw
      dislocations.
AB  - Layered double hydroxides (LDHs) are a family of two-dimensional (2D) materials
      with layered crystal structures that have found many applications. Common
      strategies to synthesize LDHs lead to a wide variety of morphologies, from
      discrete 2D nanosheets to nanoflowers. Here, we report a study of carefully
      controlled LDH nanoplate syntheses using zinc aluminum (ZnAl) and cobalt aluminum
      (CoAl) LDHs as examples and reveal their crystal growth to be driven by screw
      dislocations. By controlling and maintaining a low precursor supersaturation
      using a continuous flow reactor, individual LDH nanoplates with well-defined
      morphologies were synthesized on alumina-coated substrates, instead of the
      nanoflowers that result from uncontrolled overgrowth. The dislocation-driven
      growth was further established for LDH nanoplates directly synthesized using the
      respective metal salt precursors. Atomic force microscopy revealed screw
      dislocation growth spirals, and under transmission electron microscopy, thin CoAl
      LDH nanoplates displayed complex contrast contours indicative of strong lattice
      strain caused by dislocations. These results suggest the dislocation-driven
      mechanism is generally responsible for the growth of 2D LDH nanostructures, and
      likely other materials with layered crystal structures, which could help the
      rational synthesis of well-defined 2D nanomaterials with improved properties. 

PMID- 25870921
TI  - Molecular Mapping and Validation of SrND643: A New Wheat Gene for Resistance to
      the Stem Rust Pathogen Ug99 Race Group.
AB  - This study reports the identification of a new gene conferring resistance to the
      Ug99 lineage of races of Puccinia graminis f. sp. tritici in wheat (Triticum
      aestivum L.). Because the virulent races of stem rust pathogen continue to pose a
      serious threat in global wheat production, identification and molecular
      characterization of new resistance genes remains of utmost important to enhance
      resistance diversity and durability in wheat germplasm. Advanced wheat breeding
      line 'ND643/2*Weebill1' carries a stem rust resistance gene, temporarily
      designated as SrND643, effective against the Ug99 group of P. graminis f. sp.
      tritici races at both seedling and adult growth stages. This study was conducted
      to map the chromosomal location of SrND643 and identify closely linked molecular
      markers to allow its selection in breeding populations. In total, 123 recombinant
      inbred lines, developed by crossing ND643/2*Weebill1 with susceptible line
      'Cacuke', were evaluated for stem rust response in field nurseries at Njoro,
      Kenya, during two growing seasons in 2010, and were genotyped with DNA markers,
      including Diversity Arrays Technology, simple sequence repeats (SSR), and single
      nucleotide polymorphisms. Linkage mapping tagged SrND643 at the distal end of
      chromosome 4AL, showing close association with SSR markers Xgwm350 (0.5
      centimorgans [cM]), Xwmc219 (4.1 cM), and Xwmc776 (2.9 cM). The race specificity
      of SrND643 is different from that of Sr7a and Sr7b, indicating that the
      resistance is conferred by a gene at a new locus or by a new allele of Sr7. The
      flanking markers Xgwm350 and Xwmc219 were predictive of the presence of SrND643
      in advanced germplasm, thus validating the map location and their use in marker
      assisted selection. 

PMID- 25870922
TI  - Specificity of a Rust Resistance Suppressor on 7DL in the Spring Wheat Cultivar
      Canthatch.
AB  - The spring wheat 'Canthatch' has been shown to suppress stem rust resistance
      genes in the background due to the presence of a suppressor gene located on the
      long arm of chromosome 7D. However, it is unclear whether the suppressor also
      suppresses resistance genes against leaf rust and stripe rust. In this study, we
      investigated the specificity of the resistance suppression. To determine whether
      the suppression is genome origin specific, chromosome location specific, or rust
      species or race specific, we introduced 11 known rust resistance genes into the
      Canthatch background, including resistance to leaf, stripe, or stem rusts,
      originating from A, B, or D genomes and located on different chromosome
      homologous groups. F1 plants of each cross were tested with the corresponding
      rust race, and the infection types were scored and compared with the parents. Our
      results show that the Canthatch 7DL suppressor only suppressed stem rust
      resistance genes derived from either the A or B genome, and the pattern of the
      suppression is gene specific and independent of chromosomal location. 

PMID- 25870923
TI  - Resistance to Puccinia graminis f. sp. avenae in Barley Is Associated with the
      Rpg5 Locus.
AB  - In barley, gene Rpg5 was first identified for providing resistance to the rye
      stem rust pathogen (Puccinia graminis f. sp. secalis). A subsequent study
      determined that Rpg5 is required for rpg4-mediated resistance to the wheat stem
      rust pathogen (P. graminis f. sp. tritici) including pathotype TTKSK ("Ug99"),
      which poses a major threat to global wheat and barley production. Based on the
      effectiveness of Rpg5 against P. graminis f. sp. tritici and P. graminis f. sp.
      secalis, we assessed whether it also conferred resistance to the oat stem rust
      pathogen (P. graminis f. sp. avenae). A barley F8 recombinant inbred line (RIL)
      population was produced by crossing 'Q21861' (Rpg1 and Rpg5) with '73-G1' (Rpg1),
      which is susceptible to P. graminis f. sp. avenae, P. graminis f. sp. secalis,
      and some pathotypes of P. graminis f. sp. tritici. Seedling tests were performed
      on the F8 RIL population using Australian pathotypes of P. graminis f. sp.
      tritici, P. graminis f. sp. secalis, P. graminis f. sp. avenae, and a putative
      somatic hybrid between P. graminis f. sp. tritici and P. graminis f. sp. secalis
      known as the 'Scabrum' rust. Segregation in the responses to all rust isolates
      for the RILs was identical (50 resistant: 52 susceptible), and fitted a 1:1 ratio
      (X2=0.039, P=0.843), indicating that resistance to all isolates was
      monogenetically inherited. Screening of the RILs and the parental lines with
      perfect markers for the functional Rpg1 and Rpg5 resistance alleles indicated
      that Rpg1 was fixed, while Rpg5 was positive in all resistant lines and negative
      in all susceptible lines. This suggests that different formae speciales of P.
      graminis may share common effectors, and that the Rpg5 locus confers resistance
      to both P. graminis f. sp. tritici and P. graminis f. sp. secalis and the
      heterologous formae speciales of P. graminis, P. graminis f. sp. avenae.

PMID- 25870924
TI  - Rmg7, a New Gene for Resistance to Triticum Isolates of Pyricularia oryzae
      Identified in Tetraploid Wheat.
AB  - A single gene for resistance, designated Rmg7 (Resistance to Magnaporthe grisea
      7), was identified in a tetraploid wheat accession, St24 (Triticum dicoccum,
      KU120), against Br48, a Triticum isolate of Pyricularia oryzae. Two other wheat
      accessions, St17 (T. dicoccum, KU112) and St25 (T. dicoccum, KU122), were also
      resistant against Br48 and showed a similar disease reaction pattern to St24.
      Crosses between these resistant accessions yielded no susceptible F2 seedlings,
      suggesting that St24, St17, and St25 carry the same resistance gene. Furthermore,
      a single avirulence gene corresponding to Rmg7 was detected in a segregation
      analysis of random F1 progenies between Br48 and MZ5-1-6, an Eleusine isolate
      virulent to St24 at a higher temperature. This avirulence gene was recognized not
      only by St24, but also by St17 and St25, thus supporting the preceding results
      indicating that all three accessions carry Rmg7. This resistance gene may have
      potential in future wheat breeding programs. 

PMID- 25870925
TI  - Association mapping of seedling resistance to spot form net blotch in a worldwide
      collection of barley.
AB  - Spot form net blotch (SFNB), caused by the necrotrophic fungal pathogen
      Pyrenophora teres f. maculata, is an important foliar disease of barley in major
      production regions around the world. Deployment of adequate host resistance is
      challenging because the virulence of P. teres f. maculata is highly variable and
      characterized minor-effect resistances are typically ineffective against the
      diverse pathogen populations. A world barley core collection consisting of 2,062
      barley accessions of diverse origin and genotype were phenotyped at the seedling
      stage with four P. teres f. maculata isolates collected from the United States
      (FGO), New Zealand (NZKF2), Australia (SG1), and Denmark (DEN 2.6). Of the 2,062
      barley accessions phenotyped, 1,480 were genotyped with the Illumina barley
      iSelect chip and passed the quality controls with 5,954 polymorphic markers used
      for further association mapping analysis. Genome-wide association mapping was
      utilized to identify and map resistance loci from the seedling disease response
      data and the single nucleotide polymorphism (SNP) marker data. The best among six
      different regression models was identified for each isolate and association
      analysis was performed separately for each. A total of 138 significant (-log10P
      value>3.0) marker-trait associations (MTA) were detected. Using a 5 cM cutoff, a
      total of 10, 8, 13, and 10 quantitative trait loci (QTL) associated with SFNB
      resistance were identified for the FGO, SG1, NZKF2, and DEN 2.6 isolates,
      respectively. Loci containing from 1 to 34 MTA were identified on all seven
      barley chromosomes with one locus at 66 to 69 cM on chromosome 2H common to all
      four isolates. Six distinct loci were identified by the association mapping (AM)
      analysis that corresponded to previously characterized SFNB resistance QTL
      identified by biparental population analysis (QRpt4, QRpt6, Rpt4, Rpt6, Rpt7, and
      a QTL on 4H that was not given a provisional gene or QTL nomenclature). The 21
      putative novel loci identified may represent a broad spectrum of resistance and
      or susceptibility loci. This is the first comprehensive AM study to characterize
      SFNB resistance loci underlying broad populations of the barley host and P. teres
      f. maculata pathogen.

PMID- 25870926
TI  - Evaluation of a barley core collection for spot form net blotch reaction reveals
      distinct genotype-specific pathogen virulence and host susceptibility.
AB  - Spot form net blotch (SFNB) caused by Pyrenophora teres f. maculata is a major
      foliar disease of barley (Hordeum vulgare) worldwide. SFNB epidemics have
      recently been observed in major barley producing countries, suggesting that the
      local barley cultivars are not resistant and that virulence of the local pathogen
      populations may have changed. Here we attempt to identify sources of resistance
      effective against four diverse isolates of P. teres f. maculata collected from
      around the world. A total of 2,062 world barley core collection accessions were
      phenotyped using isolates of the pathogen collected in the United States (FGO),
      Australia (SG1), New Zealand (NZKF2), and Denmark (DEN 2.6). Isolate-specific
      susceptibility was identified in several of the barley accessions tested,
      indicating variability in both pathogen virulence and host
      resistance/susceptibility. Collectively, only 15 barley accessions were resistant
      across all isolates tested. These resistant accessions will be used to generate
      mapping populations and for germplasm development. Future research will involve
      the characterization of host resistance, pathogen virulence, and the host
      pathogen interaction associated with SFNB of barley. 

PMID- 25870927
TI  - Quantitative Analysis of Southern rice black-streaked dwarf virus in Sogatella
      furcifera and Virus Threshold for Transmission.
AB  - We investigated Southern rice black-streaked dwarf virus (SRBSDV) accumulation in
      a vector insect, the whitebacked planthopper (Sogatella furcifera), to elucidate
      the association of virus accumulation in the vector with virus transmission
      efficiency. Real-time quantitative reverse transcription polymerase chain
      reaction analysis confirmed that this virus is transmitted in a persistent
      propagative manner. SRBSDV was successfully transmitted by S. furcifera males in
      which RNA accumulation of the capsid protein gene of SRBSDV was >10(3) in the
      whole body of S. furcifera, indicating that the threshold accumulation of the
      virus RNA for virus transmission is 10(3) in an S. furcifera male. The SRBSDV
      detection rate in the immigrant population of S. furcifera was high in 2011
      (39.5%); however, most of the insects contained fewer than 10(3) RNAs of the
      capsid protein gene. This result indicates that the risk of SRBSDV epidemics
      could be estimated from the proportion of virus-transmissible S. furcifera (i.e.,
      S. furcifera that contained more than 10(3) RNAs of the virus capsid protein
      gene) rather than the SRBSDV detection rate in S. furcifera. 

PMID- 25870928
TI  - Probing the role of the ceramide acyl chain length and sphingosine unsaturation
      in model skin barrier lipid mixtures by (2)H solid-state NMR spectroscopy.
AB  - We investigated equimolar mixtures of ceramides with lignoceric acid and
      cholesterol as models for the human stratum corneum by differential scanning
      calorimetry and (2)H solid-state NMR spectroscopy. Our reference system consisted
      of lignoceroyl sphingosine (Cer[NS24]), which represents one of the ceramides in
      the human stratum corneum. Furthermore, the effect of ceramide acyl chain
      truncation to 16 carbons as in Cer[NS16] and the loss of the C4 trans double bond
      as in dihydroceramide Cer[NDS24] were studied. Fully relaxed (2)H NMR spectra
      were acquired for each deuterated component of each mixture separately, allowing
      the quantitative determination of the individual lipid phases. At skin
      temperature, the reference system containing Cer[NS24] is characterized by large
      portions of each component of the mixture in a crystalline phase, which largely
      restricts the permeability of the skin lipid barrier. The loss of the C4 trans
      double bond in Cer[NDS24] leads to the replacement of more than 25% of the
      crystalline phase by an isotropic phase of the dihydroceramide that shows the
      importance of dihydroceramide desaturation in the formation of the skin lipid
      barrier. The truncated Cer[NS16] is mostly found in the gel phase at skin
      temperature, which may explain its negative effect on the transepidermal water
      loss in atopic dermatitis patients. These significant alterations in the phase
      behavior of all lipids are further reflected at elevated temperatures. The
      molecular insights of our study may help us to understand the importance of the
      structural parameters of ceramides in healthy and compromised skin barriers. 

PMID- 25870929
TI  - On the Performance of Different Genetic Programming Approaches for the SORTING
      Problem.
AB  - In genetic programming, the size of a solution is typically not specified in
      advance, and solutions of larger size may have a larger benefit. The flexibility
      often comes at the cost of the so-called bloat problem: individuals grow without
      providing additional benefit to the quality of solutions, and the additional
      elements can block the optimization process. Consequently, problems that are
      relatively easy to optimize cannot be handled by variable-length evolutionary
      algorithms. In this article, we analyze different single- and multiobjective
      algorithms on the sorting problem, a problem that typically lacks independent and
      additive fitness structures. We complement the theoretical results with
      comprehensive experiments to indicate the tightness of existing bounds, and to
      indicate bounds where theoretical results are missing. 

PMID- 25870931
TI  - Characterization of the importance of terminal residues for southern rice black
      streaked dwarf virus P9-1 viroplasm formations.
AB  - Southern rice black-streaked dwarf virus (SRBSDV) P9-1 is involved in viroplasm
      formations in the SRBSDV-infected plants and insects. During infection, SRBSDV P9
      1 is an important protein. However, the function characterization of P9-1
      octamers in vitro and in yeast is still obscure. In this study, the secondary and
      3D structure of SRBSDV P9-1 was predicted, then SRBSDV P9-1 was expressed and
      analyzed in vitro, a size exclusion chromatography assay showed that P9-1 had the
      ability to form octamers in vitro. Mutational analysis of terminal residues
      showed that the C-terminal arm (residues 324-347) of P9-1 was importance for the
      formation of octamers. Furthermore, a yeast two-hybrid assay showed that there
      were strong interactions between the full-length P9-1s, after deleting the C
      terminal arm of P9-1, the interactions between the truncated P9-1s were
      disappeared in yeast. Collectively, the non-structural protein P9-1 played an
      essential role in self-interact viroplasm formation in vitro and in yeast, and
      the C-terminal arm region of P9-1 was important for assembling octamers in vitro.

PMID- 25870930
TI  - Four core genotypes mouse model: localization of the Sry transgene and bioassay
      for testicular hormone levels.
AB  - BACKGROUND: The "four core genotypes" (FCG) mouse model has emerged as a major
      model testing if sex differences in phenotypes are caused by sex chromosome
      complement (XX vs. XY) or gonadal hormones or both. The model involves deletion
      of the testis-determining gene Sry from the Y chromosome and insertion of an Sry
      transgene onto an autosome. It produces XX and XY mice with testes, and XX and XY
      mice with ovaries, so that XX and XY mice with the same type of gonad can be
      compared to assess phenotypic effects of sex chromosome complement in cells and
      tissues. FINDINGS: We used PCR to amplify the Sry transgene and adjacent genomic
      sequences, to resolve the location of the Sry transgene to chromosome 3 and
      confirmed this location by fluorescence in situ hybridization (FISH) of the Sry
      construct to metaphase chromosomes. Using quantitative PCR, we estimate that 12
      14 copies of the transgene were inserted. The anogenital distance (AGD) of FCG
      pups at 27-29 days after birth was not different in XX vs. XY males, or XX vs. XY
      females, suggesting that differences between XX and XY mice with the same type of
      gonad are not caused by difference in prenatal androgen levels. CONCLUSION: The
      Sry transgene in FCG mice is present in multiple copies at one locus on
      chromosome 3, which does not interrupt known genes. XX and XY mice with the same
      type of gonad do not show evidence of different androgen levels prenatally.

PMID- 25870932
TI  - Hyaluronic Acid Filler in HIV-Associated Facial Lipoatrophy: Evaluation of Tissue
      Distribution and Morphology with MRI.
AB  - OBJECTIVE: This prospective observational study evaluated magnetic resonance
      imaging (MRI) findings of hyaluronic acid (HA) injections used for the correction
      of HIV-associated facial lipoatrophy. METHODS: Ten consecutive males underwent
      subdermal HA injection (mean 1.3 +/- 0.6 ml per side) and MRI examinations prior
      to and then 1, 6 and 12 months after injection. Two radiologists blinded to the
      clinical data assessed morphologic and quantitative changes. RESULTS: MRI
      revealed HA deposition in the subdermal and deep fat compartments. A significant
      HA volume increase was observed 1 month after injection (mean increase 331%, p <
      0.0001) as compared to the injected amount. No volume reduction occurred at 12
      months (p = 0.9961). The measured bound water content did not change (p >
      0.9991), whereas skin thickness and tissue vascularization increased during the
      first 6 months (p = 0.01). CONCLUSION: Our data show that the cosmetic results of
      HA injections are caused by water binding in the deep facial fat and by a
      transient increase in vascularization and skin thickness.

PMID- 25870933
TI  - Recognition Memory Bias in Earthquake-Exposed Survivors: A Behavioral and ERP
      Study.
AB  - OBJECTIVE AND METHODS: To investigate the neural correlates of earthquake-related
      stimuli among earthquake-exposed survivors, 13 earthquake-exposed undergraduates
      without posttraumatic stress disorder (PTSD) and 13 matched controls completed a
      study-test task during which event-related potentials were recorded
      synchronously. RESULTS: The earthquake-exposed group exhibited stronger P2, P300
      and late positive component amplitudes to earthquake-related stimuli compared
      with the control group on the anterior scalp during recognition memory
      processing. In addition, earthquake-related stimuli elicited enhanced positivity
      compared with neutral stimuli in the earthquake-exposed group. CONCLUSION: The
      results indicate that earthquake-exposed subjects demonstrate recognition memory
      bias toward threatening stimuli. Even though both groups showed no PTSD symptoms,
      potential threat cues or stimuli associated with a traumatic event may trigger
      traumatic memories in this group. (c) 2015 S. Karger AG, Basel.

PMID- 25870934
TI  - Screening whole spine magnetic resonance imaging in multiple myeloma.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) is the most sensitive method for
      detecting focal spinal disease (FSD) in multiple myeloma (MM). It is unclear
      whether whole spine MRI (WS-MRI) should be employed as a screening test at
      diagnosis of MM. AIM: To determine the utility of screening WS-MRI at diagnosis
      of MM. METHODS: A retrospective analysis of data from January 2008 to January
      2013 at the Townsville Hospital was performed. At this centre, WS-MRI is used
      routinely in all newly diagnosed MM. The findings of WS-MRI in patients with and
      without an agreed guideline indication for WS-MRI were compared. Clinical
      predictors of FSD were determined. RESULTS: Seventy-one patients were included in
      the analysis. Forty-four (62%) had an agreed indication for MRI; 33 (75%) of
      these had FSD. Within this group, 17 required urgent intervention and 13 had
      spinal plasmacytomas. Within a second group without a guideline indication, 4 of
      27 (15%) were found to have FSD on MRI - none required urgent intervention and or
      had plasmacytomas. Three of eight smouldering myeloma patients were reclassified
      as symptomatic myeloma by documenting lytic lesions not identified on plain film.
      The strongest predictors of FSD were back pain (P < 0.001) and vertebral
      compression fracture (P = 0.003). CONCLUSION: WS-MRI in patients without a
      guideline indication did not detect any lesions that threatened the spinal cord.
      WS-MRI is essential in those with guideline indications. WS-MRI is of benefit to
      patients with smouldering myeloma where documentation of lesions not seen on
      plain film will result in treatment rather than observation.

PMID- 25870935
TI  - Tear Osmolarity and Ocular Surface Parameters as Diagnostic Markers of Ocular
      Graft-Versus-Host Disease.
AB  - PURPOSE: To evaluate the diagnostic value of tear osmolarity and several ocular
      surface parameters in screening for ocular surface alterations in ocular graft-vs
      host disease (GVHD) patients. DESIGN: Case-control study. METHODS: Sixty-three
      patients with ocular GVHD and 74 healthy participants were screened for ocular
      surface changes using the Ocular Surface Disease Index (OSDI), tear osmolarity,
      Schirmer test, tear break-up time (TBUT), and fluorescein corneal staining. The
      severity of ocular GVHD was diagnosed according to the National Institutes of
      Health (NIH) grading system. The diagnostic sensitivity and specificity and
      cutoff values were determined for each ocular parameter using a receiver
      operating characteristic (ROC) curve and area under the curve (AUC) analysis.
      Significance was defined at P < .05. RESULTS: The tear osmolarity, corneal
      staining score, and OSDI score gradually increased as the severity of ocular GVHD
      increased, and Schirmer value gradually decreased as the GVHD grade increased in
      severity. The Schirmer test showed greatest diagnostic sensitivity and
      specificity for ocular GVHD (92.1% sensitivity, 85.7% specificity, cutoff = 9
      mm), followed by the TBUT (87.3% sensitivity, 75.0% specificity, cutoff = 6 s),
      tear osmolarity (98.4% sensitivity, 60.7% specificity, cutoff = 311 mOsm/L),
      corneal staining score (66.7% sensitivity, 82.1% specificity, cutoff = 2), and
      OSDI score (77.8% sensitivity, 66.1% specificity, cutoff = 20.8). CONCLUSIONS:
      Multiple diagnostic modalities should be used to detect ocular surface changes in
      GVHD patients. The severity of ocular GVHD can be effectively monitored using
      tear osmolarity; however, additional studies are required.

PMID- 25870936
TI  - A new 3,4-seco-oleanane-type triterpenoid with an unusual enedione moiety from
      Hypericum ascyron.
AB  - A novel 3,4-seco-oleanane-type triterpenoid named 3,4-seco-olean-13(18)-ene-12,19
      dione-3-oic acid (1), bearing an unusual enedione moiety, was isolated from the
      aerial parts of Hypericum ascyron, together with a known feiedelane-type
      triterpenoid friedelin (2). The structure of 1 with absolute configuration was
      elucidated on the basis of spectroscopic methods and a single-crystal X-ray
      diffraction analysis. 

PMID- 25870937
TI  - Alcohol and sleep review: sound statistics and valid conclusions.

PMID- 25870939
TI  - Long-term outcomes and prognostic factors of high-risk malignant melanoma
      patients after surgery and adjuvant high-dose interferon treatment: a single
      center experience.
AB  - BACKGROUND: Surgical excision constitutes an important part of the treatment of
      local advanced malignant melanoma. Due to the high recurrence risk, adjuvant high
      dose interferon therapy is still the only therapy used in stage IIB and III high
      risk melanoma patients. METHODS: One hundred two high-risk malignant melanoma
      patients who received high-dose interferon-alpha-2b therapy were evaluated
      retrospectively. The clinicopathological features, survival times, and prognostic
      factors of the patients were determined. RESULTS: The median disease-free and
      overall survival times were 25.2 and 60.8 months, respectively. Our findings
      revealed that male gender, advanced disease stage, lymph node involvement,
      lymphatic invasion, the presence of ulceration, and a high Clark level were
      significant negative prognostic factors. CONCLUSION: In light of the favorable
      survival results obtained in this study, high-dose interferon treatment as
      adjuvant therapy for high-risk melanoma is still an efficient treatment and its
      possible side effects can be prevented by taking the necessary precautions.

PMID- 25870940
TI  - The Importance of Body Surface Area at Baseline and during Treatment in Chronic
      Myeloid Leukemia Patients Treated with Imatinib.

PMID- 25870938
TI  - Review: Insights into molecular mechanisms of disease in neurodegeneration with
      brain iron accumulation: unifying theories.
AB  - Neurodegeneration with brain iron accumulation (NBIA) is a group of disorders
      characterized by dystonia, parkinsonism and spasticity. Iron accumulates in the
      basal ganglia and may be accompanied by Lewy bodies, axonal swellings and
      hyperphosphorylated tau depending on NBIA subtype. Mutations in 10 genes have
      been associated with NBIA that include Ceruloplasmin (Cp) and ferritin light
      chain (FTL), both directly involved in iron homeostasis, as well as Pantothenate
      Kinase 2 (PANK2), Phospholipase A2 group 6 (PLA2G6), Fatty acid hydroxylase 2
      (FA2H), Coenzyme A synthase (COASY), C19orf12, WDR45 and DCAF17 (C2orf37). These
      genes are involved in seemingly unrelated cellular pathways, such as lipid
      metabolism, Coenzyme A synthesis and autophagy. A greater understanding of the
      cellular pathways that link these genes and the disease mechanisms leading to
      iron dyshomeostasis is needed. Additionally, the major overlap seen between NBIA
      and more common neurodegenerative diseases may highlight conserved disease
      processes. In this review, we will discuss clinical and pathological findings for
      each NBIA-related gene, discuss proposed disease mechanisms such as mitochondrial
      health, oxidative damage, autophagy/mitophagy and iron homeostasis, and speculate
      the potential overlap between NBIA subtypes. 

PMID- 25870941
TI  - The role of intravenous immunoglobulins in the treatment of rheumatoid arthritis.
AB  - Intravenous immunoglobulins (IVIGs) are beneficial and safe for various diseases
      other than primary immunodeficiencies. Over the years, IVIG has been given for
      autoimmune diseases as an off-label adjunct therapy. While other biologic agents
      are indicated for rheumatoid arthritis (RA), IVIG may have a role for specific
      subgroups of RA patients where anti-cytokine blockers or rituximab may be
      unwarranted. Such subgroups may include patients with vasculitis, overlap rhupus
      syndrome, severe infections with active disease, and pregnancy. In addition, IVIG
      may be considered for juvenile chronic arthritis (JCA) and adult Still's disease.
      We review the literature for IVIG treatment in RA patients and for these
      subgroups. 

PMID- 25870942
TI  - A novel mutation in the porphobilinogen deaminase gene in an extended Chinese
      family with acute intermittent porphyria.
AB  - Acute intermittent porphyria (AIP) is an autosomal dominant disorder caused by a
      partial deficiency of porphobilinogen deaminase (PBGD), the third enzyme of the
      heme biosynthetic pathway. Establishing accurate diagnoses of the patient and
      asymptomatic family members with AIP involves identifying the PBGD enzyme
      mutations directly. Genetic testing provides a precise diagnosis for the patient
      and other asymptomatic family members, and thereby proper treatments can be
      initiated to prevent the disease from progressing. In this study, we report a
      novel PBGD missense mutation, A G-to-C, at the position 988 resulting in Alanine
      to Proline (Ala330Pro), in a Chinese family. 

PMID- 25870943
TI  - The hepatitis E virus ORF1 'X-domain' residues form a putative macrodomain
      protein/Appr-1"-pase catalytic-site, critical for viral RNA replication.
AB  - The hepatitis E virus (HEV) ORF1 gene encodes the non-structural polyprotein
      wherein the 'X-domain' still remains poorly defined. Cellular X-domain associated
      macrodomain protein/ADP-ribose-1"-monophosphatase (Appr-1"-pase) activities are
      also reported in coronaviruses (CoV), including identification of its homologs in
      alpha and rubella viruses. The present study investigated the role(s) of X-domain
      residues in HEV replication cycle. In silico analysis showed a high degree of
      evolutionary conservation of X-domain (a.a. 785-942) a.a. positions wherein the N
      terminus residues 'Asn806, Asn809, His812, Gly815, Gly816, and Gly817' formed a
      potential catalytic-site homolog of CoVAppr-1"-pase. To experimentally test this
      prediction, X-domain 'active-site' residues were subjected to mutational analysis
      using the HEV-SAR55 replicon (pSK-GFP). FACS analysis of mutant RNA transfected
      S10-3 cells showed that Gly816Ala and Gly817Ala constructs completely abrogated
      HEV replication, similar to their Gly816Val and Gly817Val counterparts. However,
      'Gly815Ala' mutant replicated very poorly in contrast to 'Gly815Val' that
      completely abolished GFP synthesis. Furthermore, while 'Asn806Ala' mutant
      retained RNA replication, the 'Asn809Ala' and His812Leu mutants showed non
      viability. Notably, in a sequential-nucleotide mutation analysis, the
      dispensability of X-domain in HEV replication at transcriptional level has
      already been demonstrated (Parvez, 2013b). Taken together, the present data
      strongly argue for an essential role of X-domain residues (Asn809, His812, Gly816
      and Gly817) at post-translational level, indicating its involvement in viral
      replication. In conclusion, the speculated regulatory role of ORF1 X-domain in
      HEV replication cycle critically depends on the 'Asn, Asn, His, Gly, Gly, Gly'
      segment/secondary structure. Nevertheless, further biochemical or biophysical
      characterizations of HEV X-domain associated Appr-1"-pase activity would only
      confirm its biological significance in virus or host-pathogenesis.

PMID- 25870944
TI  - Hypertensive crisis during hemostasis of adrenal bleeding using a soft
      coagulation device.

PMID- 25870945
TI  - Oxidative state and oxidative metabolism in the brain of rats with adjuvant
      induced arthritis.
AB  - The purpose of the present study was to evaluate the oxidative status of the
      brain of arthritic rats, based mainly on the observation that arthritis induces a
      pronounced oxidative stress in the liver of arthritis rats and that morphological
      alterations have been reported to occur in patients with rheumatoid arthritis.
      Rats with adjuvant-induced arthritis were used. These animals presented higher
      levels of reactive oxygen species (ROS) in the total brain homogenate (25%
      higher) and in the mitochondria (+55%) when compared to healthy rats. The nitrite
      plus nitrate contents, nitric oxide (NO) markers, were also increased in both
      mitochondria (+27%) and cytosol (+14%). Arthritic rats also presented higher
      levels of protein carbonyl groups in the total homogenate (+43%), mitochondria
      (+69%) and cytosol (+145%). Arthritis caused a diminution of oxygen consumption
      in isolated brain mitochondria only when ascorbate was the electron donor. The
      disease diminished the mitochondrial cytochrome c oxidase activity by 55%, but
      increased the transmembrane potential by 16%. The pro-oxidant enzyme xanthine
      oxidase was 150%, 110% and 283% higher, respectively, in the brain homogenate,
      mitochondria and cytosol of arthritic animals. The same occurred with the calcium
      independent NO-synthase activity that was higher in the brain homogenate (90%)
      and cytosol (122%) of arthritic rats. The catalase activity, on the other hand,
      was diminished by arthritis in all cellular fractions (between 30 and 40%). It is
      apparent that the brain of rats with adjuvant-induced arthritis presents a
      pronounced oxidative stress and a significant injury to lipids and proteins, a
      situation that possibly contributes to the brain symptoms of the arthritis
      disease. 

PMID- 25870946
TI  - A Novel 23.1 Mb Interstitial Deletion Involving 7q22.3q32.1 in a Girl with Short
      Stature, Motor Delay, and Craniofacial Dysmorphism.
AB  - Interstitial deletions of 7q show a wide phenotypic spectrum that varies with
      respect to the location and size of the deleted region. They lead to craniofacial
      dysmorphism with intellectual disability, growth retardation, and various
      congenital defects. Here, a Mexican girl with microcephaly, facial dysmorphism,
      short stature, hand anomalies, and intellectual disability was analyzed by
      CytoScan HD array. Her phenotype was associated with a de novo 7q22.3q32.1
      deletion involving 109 loci, 57 of them listed in the OMIM database. This novel
      deletion increases the knowledge of the variability in the rupture sites of the
      region and expands the spectrum of molecular and clinical defects of the 7q
      deletion syndrome.

PMID- 25870947
TI  - Role of Hydroxytyrosol-dependent Regulation of HO-1 Expression in Promoting Wound
      Healing of Vascular Endothelial Cells via Nrf2 De Novo Synthesis and
      Stabilization.
AB  - Hydroxytyrosol (HT), an olive plant (Olea europaea L.) polyphenol, has proven
      atheroprotective effects. We previously demonstrated that heme oxygenase-1 (HO-1)
      is involved in the HT dependent prevention of dysfunction induced by oxidative
      stress in vascular endothelial cells (VECs). Here, we further investigated the
      signaling pathway of HT-dependent HO-1 expression in VECs. HT dose- and time
      dependently increased HO-1 mRNA and protein levels through the PI3K/Akt and
      ERK1/2 pathways. Cycloheximide and actinomycin D inhibited both increases,
      suggesting that HT-triggered HO-1 induction is transcriptionally regulated and
      that de novo protein synthesis is necessary for this HT effect. HT stimulated
      nuclear accumulation of nuclear factor E2-related factor 2 (Nrf2). This Nrf2
      accumulation was blocked by actinomycin D and cycloheximide whereas HT in
      combination with the 26S proteasome inhibitor MG132 enhanced the accumulation. HT
      also extended the half-life of Nrf2 proteins by decelerating its turnover.
      Moreover, HO-1 inhibitor, ZnppIX and CO scavenger, hemoglobin impaired HT
      dependent wound healing while CORM-2, a CO generator, accelerated wound closure.
      Together, these data demonstrate that HT upregulates HO-1 expression by
      stimulating the nuclear accumulation and stabilization of Nrf2, leading to the
      wound repair of VECs crucial in the prevention of atherosclerosis.

PMID- 25870948
TI  - CYP2J2 and EETs protect against lung ischemia/reperfusion injury via anti
      inflammatory effects in vivo and in vitro.
AB  - BACKGROUND: Injurious inflammatory response is critical to the development of
      lung ischemia/reperfusion injury (LIRI). The cytochrome P450 epoxygenase 2J2
      (CYP2J2) metabolizes arachidonic acid to epoxyeicosatrienoic acids (EETs), which
      exert an anti-inflammatory effect on the cardiovascular system. We therefore
      cytochrome hypothesized that CYP2J2 overexpression and pretreatment with
      exogenous EETs may have the potential to reduce LIRI. METHODS: A rat model was
      used to mimic the condition of LIRI by clamping the left pulmonary hilum for 60
      minutes, followed by reperfusion for 2 hours. Moreover, we developed a cell model
      using human pulmonary artery endothelial cells by anoxia for 8 hours, followed by
      reoxygenation for 16 hours to determine the anti-inflammatory effect and
      mechanism of CYP2J2 overexpression and exogenous 11,12-EET. RESULTS: Lung
      ischemia/reperfusion increased lung wet/dry and lung weight/body weight ratios,
      protein concentration in bronchoalveolar lavage fluid and concentrations of pro
      inflammatory, including mediators in serum IL-1beta, IL-8, TNF-alpha, sP- and sE
      selectin, and decreased concentration of anti-inflammatory mediator IL-10.
      Ischemia/reperfusion also leaded to pulmonary edema and inflammation under light
      microscopy. Furthermore, activation of NF-kappaB p65 and degradation of
      IkappaBalpha were remarkably increased in ischemia/reperfusion lung tissues.
      While CYP2J2 overexpression significantly inhibited the above effects (p<0.05).
      In vitro data further confirmed the anti-inflammatory effect of CYP2J2
      overexpression and 11,12-EET, an effect that may probably be mediated by
      PPARgamma activation. CONCLUSION: CYP2J2 overexpression and administration of
      exogenous EETs can protect against LIRI via anti-inflammatory effects. This can
      be a novel potential strategy for prevention and treatment of LIRI.

PMID- 25870949
TI  - Authors' response to Li et al. Obes   Facts 2015;8:DOI: 10.159/000381434.

PMID- 25870950
TI  - Management of interstitial ectopic pregnancy with intravenous methotrexate: An
      extended study of a standardised regimen.
AB  - BACKGROUND: Interstitial ectopic pregnancy is a rare but potentially life
      threatening condition. Of the three management options for this condition
      (expectant, medical and surgical treatment) methotrexate therapy in several
      regimens has been reported to be effective and beneficial. AIM: To assess the
      safety and efficacy of intravenous bolus and infusion of methotrexate with
      folinic acid rescue for the treatment of interstitial ectopic pregnancy.
      MATERIALS AND METHODS: A retrospective cohort study of women with interstitial
      ectopic pregnancy treated with methotrexate at the Royal Brisbane and Women's
      Hospital from April 2000 to December 2012. The treatment regimen comprised of a
      bolus dose of methotrexate 100 mg followed by 200 mg of methotrexate infusion
      over 12 h. Four doses of 15 mg oral folinic acid rescue were given post
      treatment. Success of methotrexate therapy was confirmed by either a negative
      serum beta-human chorionic gonadotropin (beta-hCG) level or subsequent uneventful
      pregnancy. RESULTS: Of 33 women with interstitial ectopic pregnancy who were
      treated with this regimen, 31 (93.9%) were treated successfully, including women
      with a high beta-hCG level up to 106 634 IU/L and the presence of fetal cardiac
      activity. Minor side effects were documented in three cases. CONCLUSIONS:
      Intravenous methotrexate therapy with folinic acid rescue is well tolerated and
      highly effective.

PMID- 25870951
TI  - The danger within: the role of genetic, behavioural and ecological factors in
      population persistence of colour polymorphic species.
AB  - Polymorphic species have been the focus of important work in evolutionary
      biology. It has been suggested that colour polymorphic species have specific
      evolutionary and population dynamics that enable them to persist through
      environmental changes better than less variable species. We suggest that recent
      empirical and theoretical work indicates that polymorphic species may be more
      vulnerable to extinction than previously thought. This vulnerability arises
      because these species often have a number of correlated sexual, behavioural, life
      history and ecological traits, which can have a simple genetic underpinning. When
      exacerbated by environmental change, these alternate strategies can lead to
      conflict between morphs at the genomic and population levels, which can directly
      or indirectly affect population and evolutionary dynamics. In this perspective,
      we identify a number of ways in which the nature of the correlated traits, their
      underpinning genetic architecture, and the inevitable interactions between colour
      morphs can result in a reduction in population fitness. The principles
      illustrated here apply to all kinds of discrete polymorphism (e.g. behavioural
      syndromes), but we focus primarily on colour polymorphism because they are well
      studied. We urge further empirical investigation of the genetic architecture and
      interactions in polymorphic species to elucidate the impact on population
      fitness. 

PMID- 25870952
TI  - Moving beyond luminal stenosis: imaging strategies for stroke prevention in
      asymptomatic carotid stenosis.
AB  - BACKGROUND: With progressive improvements in medical therapy and resultant
      reductions in stroke risk, luminal stenosis criteria are no longer adequate to
      inform decisions to pursue surgical revascularization in patients with
      asymptomatic carotid artery stenosis. SUMMARY: In this evidence-based review, we
      discuss the imaging-based risk stratification strategies that take into account
      factors beyond luminal stenosis measurements, including cerebral hemodynamics and
      plaque composition. The existing literature lends support to the use of certain
      imaging tests in patients with asymptomatic carotid stenosis including
      cerebrovascular reserve testing, MRI of plaque composition, ultrasound of plaque
      echolucency, and transcranial Doppler evaluation for microemboli. The highest
      quality evidence thus far in the literature includes only systematic reviews and
      meta-analyses of cohort studies with no randomized trials having yet been
      performed to show how these newer imaging biomarkers could be used to inform
      treatment decisions in asymptomatic carotid stenosis. Beyond the need for
      randomized trials, there are additional important steps needed to improve the
      relevance of evidence supporting risk assessment strategies. Imaging studies
      evaluating the risk of stroke in carotid disease should clearly define
      asymptomatic versus symptomatic disease, use uniform definitions of clearly
      defined outcome measures such as ipsilateral stroke, ensure that imaging
      interpretations are performed in a manner blinded to treatments and other risk
      factors, and include cohorts which are on modern intensive medical therapy. Such
      studies of risk stratification for asymptomatic carotid stenosis will be most
      valuable if they can integrate multiple high-risk features (including clinical
      risk factors) into a multi-factorial risk assessment strategy in a manner that is
      relatively simple to implement and generalizable across a wide range of practice
      settings. Key Messages: Together, modern imaging strategies allow for a more
      mechanistic assessment of stroke risk in carotid disease compared to luminal
      stenosis measurements alone, which, with further validation in randomized
      controlled trials, may improve current efforts at stroke prevention in
      asymptomatic carotid stenosis.

PMID- 25870953
TI  - The anticancer activity of the substituted pyridone-annelated isoindigo (5'-Cl)
      involves G0/G1 cell cycle arrest and inactivation of CDKs in the promyelocytic
      leukemia cell line HL-60.
AB  - BACKGROUND/AIMS: The antileukemic potential of isoindigos make them desired
      candidates for understanding their mechanism of action. We have recently
      synthesized a novel group of pyridone-annelated isoindigos and identified the
      derivative 5'-Cl that is cytotoxic to various cancer cell lines. In the present
      study, we analyzed the effect of this compound on cell cycle of the promyelocytic
      leukemia cell line HL-60. METHODS: HL-60 cells were treated with 5'-Cl and its
      effect on cell cycle stages were determined by flow cytometry. Expression of
      cyclins, cyclin dependent kinases (CDKs) and cyclin kinase inhibitors (CKIs) were
      determined by Western blotting, and activation of CDKs was studied using kinase
      assays. RESULTS: 5'-Cl remarkably arrested cell cycle in HL-60 cells at the G0/G1
      phase in a dose and time-dependent manner. Furthermore, 5'-Cl treatment
      significantly inhibited expression of D-cyclins, CDK2 and CDK4 and suppressed
      phosphorylation of the retinoblastoma protein Rb, whereas it increased the level
      of CKI p21. Molecular modelling experiments show that 5'-Cl may compete with ATP
      for binding to the catalytic subunit of CDK2 and CDK4 that could lead to
      inhibition of these enzymes. Indeed, 5'-Cl inhibited the kinase activity of CDK2
      and CDK4 both in cell free systems and in treated cells. 5'-Cl also inhibited
      cell cycle progression in several other tumor cell lines. CONCLUSION: We
      demonstrate the potent inhibitory effects of 5'-Cl on HL-60 cells could be
      mediated by arresting cells in the G0/G1 phase.

PMID- 25870954
TI  - An anthropomorphic sonography phantom for the evaluation of mechatronic devices
      for heart surgery.
AB  - Surgical assistance systems are used to make surgical procedures more precise.
      The integration of automated intra-operative imaging in surgical interventions
      can be seen as an important step to further improve patient safety. An automatic
      soft tissue manipulation system with mechatronic assistance using endoscopic
      Doppler guidance was developed for minimally invasive coronary artery bypass
      surgery. To facilitate the complicated development process of the mechatronic
      system, we manufactured and validated an anthropomorphic phantom. A three
      compartment model including soft tissue and a vessel system were manufactured for
      the phantom. Blood flow simulation was implemented using a pump and blood
      mimicking fluid in a closed circuit. Eighteen physicians evaluated the anatomical
      and physiological validity of the phantom in a study. The average rating of the
      anatomy, as well as the physiology, was good, although particular aspects of the
      phantom have shown a need for improvement. The validation study provided valuable
      information on limits and problems concerning the phantom and its applicability
      for the evaluation of the development steps of the mechatronic system. We showed
      how to develop and validate a phantom for the evaluation of a surgical assistance
      system with intraoperative imaging. The described concepts can be applied to
      similar developmental procedures and help generate a goal-driven and efficient
      development. 

PMID- 25870955
TI  - Calcium phosphate/microgel composites for 3D powderbed printing of ceramic
      materials.
AB  - Composites of microgels and calcium phosphates are promising as drug delivery
      systems and basic components for bone substitute implants. In this study, we
      synthesized novel composite materials consisting of pure beta-tricalcium
      phosphate and stimuli-responsive poly(N-vinylcaprolactam-co-acetoacetoxyethyl
      methacrylate-co-vinylimidazole) microgels. The chemical composition, thermal
      properties and morphology for obtained composites were extensively characterized
      by Fourier transform infrared, X-ray photoelectron spectroscopy, IGAsorp moisture
      sorption analyzer, thermogravimetric analysis, granulometric analysis, ESEM,
      energy dispersive X-ray spectroscopy and TEM. Mechanical properties of the
      composites were evaluated by ball-on-three-balls test to determine the biaxial
      strength. Furthermore, initial 3D powderbed-based printing tests were conducted
      with spray-dried composites and diluted 2-propanol as a binder to evaluate a new
      binding concept for beta-tricalcium phosphate-based granulates. The printed
      ceramic bodies were characterized before and after a sintering step by ESEM. The
      hypothesis that the microgels act as polymer adhesive agents by efficient
      chemical interactions with the beta-tricalcium phosphate particles was confirmed.
      The obtained composites can be used for the development of new scaffolds. 

PMID- 25870956
TI  - An experimental-nonlinear finite element study of a balloon expandable stent
      inside a realistic stenotic human coronary artery to investigate plaque and
      arterial wall injury.
AB  - The stresses induced within plaque tissues and arterial layers during stent
      expansion inside an atherosclerotic artery can be exceeded from the yield
      stresses of those tissues and, consequently, lead to plaque or arterial wall
      rupture. The distribution and magnitude of the stresses in the plaque-artery
      stent structure might be distinctly different for different plaque types. In this
      study, the mechanical properties of six healthy and atherosclerotic human
      coronary arteries were determined for application in plaque and arterial
      vulnerability assessment. A nonlinear finite element simulation based on an Ogden
      material model was established to investigate the effect of plaque types on the
      stresses induced in the arterial wall during implantation of a balloon expandable
      coronary stent. The atherosclerotic artery was assumed to consist of a plaque and
      normal arterial tissues on its outer side. The results indicated a significant
      influence of plaque types on the maximum stresses induced within the plaque wall
      and arterial wall during stenting but not when computing maximum stress on the
      stent. The stress on the stiffest calcified plaque wall was 3.161 MPa, whereas
      cellular and hypocellular plaques showed relatively less stress on their wall.
      The highest von Mises stresses within the arterial wall were observed on the
      hypocellular plaque, whereas the lowest stresses were seen to be located in the
      calcified and cellular plaques. Although the computed stresses on the arterial
      wall for the calcified and cellular plaques were not high enough to invoke a
      rupture, the stress on the hypocellular plaque was relatively higher than that of
      the strength of the arterial wall. These findings may have implications not only
      for understanding the stresses induced in plaque and the arterial wall, but also
      for developing surgeries such as balloon-angioplasty and stenting. 

PMID- 25870957
TI  - Communication about maternal-fetal surgery for myelomeningocele and congenital
      diaphragmatic hernia: preliminary findings with implications for informed consent
      and shared decision-making.
AB  - OBJECTIVE: To examine the style and content of consultations for maternal-fetal
      surgery and draw conclusions about best practices for informed consent and shared
      decision-making. STUDY DESIGN: Qualitative study of 15 h-long consultations with
      women diagnosed with fetal myelomeningocele (MMC, n=11) or congenital
      diaphragmatic hernia (CDH, n=4) who were potential candidates for maternal-fetal
      surgery at a large children's hospital in the Southwestern US. RESULTS: Major
      findings were that physicians tended to discuss the risks of fetal prognosis
      qualitatively more often than quantitatively (70% compared to 30%) and when
      mortality was a risk the "positive" (percentage survival) frame was always given
      rather than the morality frame. On average, families only talked 15% of the time
      and 45% of all their questions were about diagnostic or surgical procedure
      clarification. CONCLUSION: Efforts should be made to minimize qualitative
      presentation of risk, which can be vague and confusing to patients. Both survival
      and mortality frames should be used to avoid biased decision-making.
      Communication and decision support tools that facilitate more shared decision
      making between families and physicians are needed.

PMID- 25870958
TI  - The role of apolipoprotein E polymorphism in improving dyslipidemia in obese
      adolescents following physical exercise and National Cholesterol Education
      Program Step II intervention.
AB  - BACKGROUND: Lifestyle changes are important factors for managing dyslipidemia
      before considering blood lipid-lowering drugs. However, genetic factors can
      influence the response outcome. OBJECTIVE: We aimed to determine a dyslipidemia
      management strategy in obese adolescents. PATIENTS AND METHODS: A total of 60
      dyslipidemic obese adolescents received physical exercise and the NCEP step II
      diet for 28 days. Apolipoprotein E (apo E) genotypes and blood lipid levels were
      compared before and after interventions. RESULTS: The apo E3/E3 genotype was
      found to be common in all subjects. Mean levels of total cholesterol,
      triglyceride, and low-density lipoprotein-cholesterol (LDL-C) improved in
      subjects with the E3 allele after the intervention, but not the E2 allele. Total
      cholesterol and LDL-C, but not triglyceride levels, improved in subjects with the
      E4 allele. DISCUSSION: Apo E alleles might influence improvement in lipid
      profiles after diet and exercise interventions. These results could inform
      personalized dyslipidemia management in obese adolescents, to determine which
      subjects would benefit from blood lipid-lowering drugs.

PMID- 25870959
TI  - Role of Toll-like receptor/MYD88 signaling in neurodegenerative diseases.
AB  - Toll-like receptors (TLRs) are important innate immune proteins, and the
      activation of the TLRs results in the activation of intracellular signaling
      pathways, leading to the expression of proinflammatory cytokines that are
      essential to the identification and clearance of invading pathogens. TLR
      signaling occurs through adaptor proteins, most commonly myeloid differentiation
      primary response gene 88 (MyD88). It is now known that immune surveillance and
      inflammatory responses occur in neurodegenerative diseases and TLR/MYD88
      signaling plays a critical role in these diseases. The included studies suggest a
      contribution for this signaling to the pathophysiology of Alzheimer's disease,
      Parkinson's disease, amyotrophic lateral sclerosis, multiple system atrophy, and
      related disorders. In this review, a discussion of the recent findings in this
      field is presented. 

PMID- 25870961
TI  - Spinal cord injury: overview of experimental approaches used to restore locomotor
      activity.
AB  - Spinal cord injury affects more than 2.5 million people worldwide and can lead to
      paraplegia and quadriplegia. Anatomical discontinuity in the spinal cord results
      in disruption of the impulse conduction that causes temporary or permanent
      changes in the cord's normal functions. Although axonal regeneration is limited,
      damage to the spinal cord is often accompanied by spontaneous plasticity and axon
      regeneration that help improve sensory and motor skills. The recovery process
      depends mainly on synaptic plasticity in the preexisting circuits and on the
      formation of new pathways through collateral sprouting into neighboring
      denervated territories. However, spontaneous recovery after spinal cord injury
      can go on for several years, and the degree of recovery is very limited.
      Therefore, the development of new approaches that could accelerate the gain of
      motor function is of high priority to patients with damaged spinal cord. Although
      there are no fully restorative treatments for spinal injury, various
      rehabilitative approaches have been tested in animal models and have reached
      clinical trials. In this paper, a closer look will be given at the potential
      therapies that could facilitate axonal regeneration and improve locomotor
      recovery after injury to the spinal cord. This article highlights the application
      of several interventions including locomotor training, molecular and cellular
      treatments, and spinal cord stimulation in the field of rehabilitation research.
      Studies investigating therapeutic approaches in both animal models and
      individuals with injured spinal cords will be presented. 

PMID- 25870960
TI  - Autophagy in Alzheimer's disease.
AB  - Autophagy is a vesicle and lysosome-mediated degradative pathway that is
      essential for protein homeostasis and cell health. In particular, compared to
      nonneuronal cells, neurons are dependent on high basal autophagy for survival.
      There is emerging agreement that defects in autophagy are likely to contribute to
      the neurodegenerative processes in numerous diseases, including Alzheimer's
      disease (AD). Autophagy-lysosome defects occur early in the pathogenesis of AD
      and have been proposed to be a significant contributor to the disease process.
      Given the fact that autophagy deficits are likely major contributors to the
      etiology of AD, the focus of this review will be on recent studies that support a
      role for autophagy deficits in AD. 

PMID- 25870962
TI  - How to define a significant deviation from the expected internal quality control
      result.
AB  - BACKGROUND: Internal quality control (IQC) is an everyday practice described in
      several documents. Its planning requires the definition of quality goals and a
      documentation system able to provide alarms as soon as the goals are not reached.
      We propose the use of the uncertainty approach to develop an effective alarm
      system. METHODS: The use of the uncertainty information to verify the conformity
      to specifications is described. A top-down approach to the definition of the
      uncertainty of the method is described. Once the uncertainty is calculated, the
      complete measurement result (result +/- expanded uncertainty) is compared with
      the maximum permissible error (quality goal). An alternative and more immediate
      presentation is obtained defining an "acceptance zone" derived from the maximum
      permissible error reduced on either sides by expanded uncertainty. This approach
      is applied to two analytes: glucose and creatinine. RESULTS: The relationship
      between quality goal and expanded uncertainty defines the width of the acceptance
      zone; if uncertainty is equal or larger than the quality goal, the goal is not
      attainable. CONCLUSIONS: The proposed approach uses an information, expanded
      uncertainty, that each laboratory seeking ISO 15189 accreditation should already
      have. The data presentation is immediate and easy to interpret allowing a direct
      comparison between the performance of the method and the quality goals.

PMID- 25870963
TI  - Analytical challenges related to the use of biomarker ratios for the biological
      diagnosis of Alzheimer's disease.

PMID- 25870964
TI  - Performance criteria for combined uncertainty budget in the implementation of
      metrological traceability.
AB  - The measurement uncertainty budget should combine the uncertainty of higher order
      references, the uncertainty of commercial system calibration, the system
      imprecision and individual laboratory performance in terms of variability. Here
      we recommend that no more than one third of the total uncertainty budget,
      established by appropriate analytical performance specifications, is consumed by
      the uncertainty of references and approximately 50% of the total budget consumed
      by the manufacturer's calibration and value transfer protocol. The remaining 50%
      should be available for the commercial system imprecision (including the batch to
      batch variation of the reagents) and individual laboratory performance in order
      to fulfil the uncertainty goal. For commercial systems to work properly, in vitro
      diagnostics (IVD) manufacturers will need to take more responsibility and ensure
      the traceability of the combination of platform, reagents, calibrators and
      control materials for system alignment verification that only as such (as a
      whole) are certified ("CE marked") by the manufacturer itself in terms of
      traceability to the selected reference measurement system. Particularly, IVD
      manufacturers should report the combined (expanded) uncertainty associated with
      their calibrators when used in conjunction with other components of their
      analytical system (platform and reagents). This is more than what they are
      currently providing as traceability and uncertainty information.

PMID- 25870965
TI  - Elevated circulating ghrelin, but not peptide YY(3-36) levels, in term neonates
      with infection.
AB  - BACKGROUND: Early diagnosis and treatment of neonatal infection is important to
      prevent morbidity and mortality. The gastrointestinal tract-derived hormones
      ghrelin and peptide YY (PYY), which participate in the regulation of food intake
      and energy balance, may also play roles in the inflammatory response. Their
      involvement in neonatal infection is not known. METHODS: Plasma ghrelin and PYY(3
      36) levels were serially measured (by ELISA) on Days 0, 1, 2, 3 and 7 following
      admission in 36-term neonates with febrile infection (22 of them were septic) and
      once in 20 healthy term neonates of similar postnatal age and gender
      distribution, as controls. Associations of ghrelin and PYY(3-36) levels with
      clinical and laboratory parameters, including anthropometrics, fever, leukocyte
      and platelet counts, serum glucose, C-reactive protein (CRP) and serum amyloid A
      levels, were assessed. RESULTS: Plasma ghrelin levels were significantly higher
      in infected neonates than in controls at each study day (p=0.009), whereas PYY(3
      36) levels did not differ significantly between patients and controls at any day.
      In infected neonates, ghrelin levels on admission correlated negatively with
      serum glucose levels (p=0.003), whereas fever change during the course of
      infection was significantly associated with change of ghrelin levels (p=0.01).
      Receiver operating characteristic analysis of ghrelin levels resulted in
      significant areas under the curve (AUC) for detecting infected neonates on
      admission (AUC=0.728, p=0.005). CONCLUSIONS: Circulating ghrelin, but not PYY(3
      36), levels are increased in neonates with infection, possibly reflecting and/or
      participating in the inflammatory process.

PMID- 25870966
TI  - Association between physical fitness and mean platelet volume in professional
      soccer players.

PMID- 25870967
TI  - Value of a commercial kit for detecting anti-C1q autoantibodies and correlation
      with immunological and clinical activity of lupus nephritis.
AB  - BACKGROUND: The association of anti-C1q antibodies (anti-C1q) with the renal
      activity of lupus nephritis (LN) and the methods for their determination is still
      a matter of debate. METHODS: In 116 serum samples of 66 patients with biopsy
      proven LN, we aimed: 1) to compare the results of the determination of anti-C1q
      obtained by a commercial kit with a clinically validated in-house ELISA; 2) to
      evaluate the correlation of anti-C1q with the most important immunological and
      clinical parameters employed in LN, i.e., antibodies to dsDNA (anti-dsDNA), C3
      and C4 complement component, haemoglobin and haematuria. RESULTS: Good
      correlation and agreement between the two methods (r=0.81, p<0.0001; contingency
      coefficient=0.70, p<0.0001, respectively) were demonstrated. No differences were
      observed between the two assays by ROC curves comparison. Anti-C1q levels were
      significantly higher in patients with active LN [44 arbitrary units (AUs)] in
      comparison to those with inactive LN (23 AUs, p=0.047) and significantly
      correlated with anti-dsDNA (r=0.44, p<0.0001), complement fractions (C3: r=-0.33,
      p=0.001; C4: r=-0.29, p=0.003), haemoglobin levels (r=-0.34, p=0.0004) and the
      number of urinary red blood cells (r=0.26, p=0.01). CONCLUSIONS: Our results
      suggest the validity of this commercial assay in detecting anti-C1q and confirm
      the association of anti-C1q with renal involvement of LN and the importance of
      introducing this parameter in the analytical panel for the evaluation of LN
      activity.

PMID- 25870968
TI  - Performance criteria for reference measurement procedures and reference
      materials.
AB  - The concept of metrological traceability of measurement results to property
      values assigned to measurement standards of higher metrological order or to the
      International System of Units (SI) through sequential calibrations, using
      reference materials and reference measurement procedures, plays a key role in
      ensuring that end user measurement procedures perform at an acceptable level in
      the clinical context. The aim is that measurement results produced over time or
      by different end users or with different end user measurement procedures for the
      same measurand will be equivalent within their corresponding uncertainties. These
      goals can only be reached under certain conditions and if requirements laid down
      in international standards on calibration concepts, reference measurement
      procedures and reference materials are fulfilled. Calibration hierarchies have to
      be implemented correctly and parameters contributing to measurement uncertainty
      and systematic bias need to be controlled and eliminated, respectively, by
      technically improving methods and reference materials and intermediate
      calibrators used for effectively achieving equivalence of measurement results and
      for meeting analytical performance requirements for in vitro diagnostic devices.

PMID- 25870969
TI  - Daily communication decreases the number of pre-analytical errors in primary
      care.

PMID- 25870970
TI  - Extracellular matrix in obesity - cancer interactions.
AB  - Obesity or overweight is a risk factor for several health disorders such as type
      2 diabetes, hypertension, and certain cancers. Furthermore, obesity affects
      almost all body systems including the extracellular matrix (ECM) by generating a
      pro-inflammatory environment, which are associated with abnormal secretions of
      several cytokines or hormonal substances, for example, insulin-like growth
      factors (IGFs), leptin, and sex hormones. These chemical mediators most likely
      have a great impact on the ECM. Accumulating evidence suggests that both obesity
      and ECM can influence tumor growth and progression through a number of chemical
      mediators. Conversely, cells in the connective tissue, namely fibroblasts and
      macrophages, support and aggravate the inflammatory situation in obesity by
      releasing several cytokines or growth factors such as vascular endothelial growth
      factor, epidermal growth factor, and transforming growth factor-beta (TGF-beta).
      A wide range of functions are performed by TGF-beta in normal health and
      pathological conditions including tumorigenesis. Breast cancer in postmenopausal
      women is a classic example of obesity-related cancer wherein several of these
      conditions, for example, higher levels of pro-inflammatory cytokines, impairment
      in the regulation of estrogen and growth factors, and dysregulation of different
      ECM components may favor the neoplastic process. Aberrant expressions of ECM
      components such as matrix metalloproteinases or matricellular proteins in both
      obesity and cancer have been reported by many studies. Nonstructural
      matricellular proteins, viz., thrombospondins, secreted protein acidic and rich
      in cysteine (SPARC), and Cyr61-CTGF-Nov (CCN), which function as modulators of
      cell-ECM interactions, exhibit protean behavior in cancer. Precise understanding
      of ECM biology can provide potential therapeutic targets to combat obesity
      related pathologies. 

PMID- 25870971
TI  - The direct and indirect effects of corticosterone and primary adipose tissue on
      MCF7 breast cancer cell cycle progression.
AB  - BACKGROUND: Breast cancer is the second leading cause of cancer-related mortality
      in women. Glucocorticoids (GCs) have the potential to directly affect breast
      cancer or indirectly via changes to the tumor growth microenvironment a breast
      cancer is exposed to. The role of GCs in breast cancer progression by direct and
      indirect means are not fully understood. AIM: To study the direct and indirect
      effects of GCs on breast cancer cell cycle regulation. METHODS: MCF7 breast
      cancer cells were incubated with increasing concentrations of corticosterone
      (CORT) to investigate the direct effects. In addition, MCF7 cells were cultured
      in conditioned media (CM) from primary adipose tissue excised from CORT
      supplemented lean and obese male rats. RESULTS: CORT alone resulted in dose
      dependent increases in p27 and hypophosphorylated retinoblastoma protein (Rb)
      which was accompanied by a reduction in the number of cells in S-phase. CM
      prepared from adipose tissue overrode these direct CORT effects, suggesting that
      the tumor growth microenvironment created in the CM dominates MCF7 cell cycle
      regulation. CONCLUSIONS: The direct inhibitory effects of CORT on cancer cell
      cycle progression are largely limited by the hormone's effects on adipose tissue
      biology.

PMID- 25870972
TI  - Suggested roles for microRNA in tumors.
AB  - MicroRNAs are short non-coding RNA molecules encoded by distinct genes involved
      in the posttranscriptional regulation of gene expression. Forming part of the
      epigenetic machinery, microRNAs are involved in several aspects of tumorigenesis.
      Deregulation of microRNA expression is a common feature of tumors. Overexpressed
      oncogenic and underexpressed tumor suppressor microRNAs have been described in
      many different tumors. MicroRNAs are released from tumors that might affect other
      cells within and outside the tumor. Circulating microRNAs might also be involved
      in a tumor surveillance mechanism. In this short overview, some important aspects
      of microRNA in tumors are discussed. 

PMID- 25870973
TI  - Therapeutic interventions using a combination of Telmisartan and omega 3-fatty
      acids in sodium arsenite-induced vascular endothelial dysfunction in rats:
      modulation through ATP-sensitive K+ channels and eNOS.
AB  - BACKGROUND: Effective diet/drug combinations may show additive or synergistic
      effects in reducing endothelial risk factors vis-a-vis monotherapies. The study
      evaluated the effect of combined therapy of Telmisartan and omega 3-fatty acids
      in sodium arsenite-induced vascular endothelial dysfunction (VED) in rats.
      METHODS: Forty-eight male Wistar rats (180-220 g) were randomized into eight
      groups; control, sodium arsenite (1.5 mg/kg/day) exposed, sodium arsenite
      exposure followed by treatment with Telmisartan, omega 3-fatty acids, the
      combination and/or endothelial modulators for 2 weeks depending on the allocated
      group. VED was assessed by estimating vascular reactivity. Serum thiobarbituric
      acid-reactive substances (TBARS), nitrite/nitrate levels, reduced glutathione
      (GSH) levels, superoxide dismutase (SOD) activity, serum cholesterol and
      triglyceride levels were also determined. RESULTS: Sodium arsenite produced VED
      by attenuating acetylcholine-induced endothelial relaxation (% Rmax= 45.36),
      decreasing levels of serum nitrite/nitrate (9.28 MUM/mg protein), GSH (16.06
      MUg/mg of protein), SOD activity (30.69 units/mg protein) and increasing TBARS
      (0.19 uM/mg protein) compared with control group. The combined therapy with
      Telmisartan (10 mg/kg/day) and omega 3-fatty acids (180 mg/kg/day) (% Rmax =
      80.93, 13.09 uM/mg protein, 25.93 MUg/mg of protein, 57.84 units/mg protein and
      0.08 uM/mg protein, respectively) significantly abolished the respective
      derangements induced by sodium arsenite. Further, this combination significantly
      prevented rise in serum cholesterol and triglyceride levels that was induced by
      sodium arsenite. However, the ameliorative effects of this combination were
      abated by N-omega-nitro-L-arginine methyl ester (L-NAME) and glibenclamide.
      CONCLUSIONS: Combined therapy of Telmisartan and omega 3-fatty acids attenuated
      VED, by activating enzyme nitric oxide synthase (eNOS) through opening of ATP
      sensitive K(+) channels.

PMID- 25870975
TI  - How long is too long? The lack of consensus regarding the post-concussion
      syndrome diagnosis.
AB  - BACKGROUND/AIM: A standard definition of Post-concussion Syndrome (PCS) does not
      exist. The objective was to determine consensus regarding the definition of PCS
      among physician members of the American College of Sports Medicine (ACSM).
      METHODS: Physician members of the ACSM were sent an electronic survey to
      determine opinions regarding the PCS diagnosis. RESULTS: Five hundred and ninety
      seven physicians completed the survey. When asked the minimum duration of
      symptoms required to diagnose PCS, respondents answered: <2 weeks (26.6%), 2
      weeks to 1 month (20.4%), 1-3 months (33%) and >3 months (11.1%). Physicians who
      see >=10% concussion patients in their practise, as well as physicians whose
      concussion population consists of >50% paediatric patients, were more likely to
      require >1 month of symptoms (p < 0.001). When asked the minimum number of
      symptoms required to diagnose PCS, responses varied: one symptom (55.9%), two
      symptoms (17.6%), three symptoms (14.6%) and four or more symptoms (3.2%).
      Respondents from the US were more likely than non-US respondents to require only
      one symptom for the PCS diagnosis (p = 0.01). CONCLUSIONS: There is a lack of
      consensus regarding the definition of PCS among physician members of the ACSM. A
      standard definition would improve consistency in concussion research and in
      clinical practise.

PMID- 25870974
TI  - Lung Cancer and Exposure to Nitrogen Dioxide and Traffic: A Systematic Review and
      Meta-Analysis.
AB  - BACKGROUND AND OBJECTIVE: Exposure to traffic-related air pollutants is an
      important public health issue. Here, we present a systematic review and meta
      analysis of research examining the relationship of measures of nitrogen oxides
      (NOx) and of various measures of traffic-related air pollution exposure with lung
      cancer. METHODS: We conducted random-effects meta-analyses of studies examining
      exposure to nitrogen dioxide (NO2) and NOx and its association with lung cancer.
      We identified 20 studies that met inclusion criteria and provided information
      necessary to estimate the change in lung cancer per 10-MUg/m3 increase in
      exposure to measured NO2. Further, we qualitatively assessed the evidence of
      association between distance to roadways and traffic volume associated with lung
      cancer. RESULTS: The meta-estimate for the change in lung cancer associated with
      a 10-MUg/m3 increase in exposure to NO2 was 4% (95% CI: 1%, 8%). The meta
      estimate for change in lung cancer associated with a 10-MUg/m3 increase in NOx
      was similar and slightly more precise, 3% (95% CI: 1%, 5%). The NO2 meta-estimate
      was robust to different confounding adjustment sets as well as the exposure
      assessment techniques used. Trim-and-fill analyses suggest that if publication
      bias exists, the overall meta-estimate is biased away from the null. Forest plots
      for measures of traffic volume and distance to roadways largely suggest a modest
      increase in lung cancer risk. CONCLUSION: We found consistent evidence of a
      relationship between NO2, as a proxy for traffic-sourced air pollution exposure,
      with lung cancer. Studies of lung cancer related to residential proximity to
      roadways and NOx also suggest increased risk, which may be attributable partly to
      air pollution exposure. The International Agency for Research on Cancer recently
      classified outdoor air pollution and particulate matter as carcinogenic (Group
      1). These meta-analyses support this conclusion, drawing particular attention to
      traffic-sourced air pollution. CITATION: Hamra GB, Laden F, Cohen AJ, Raaschou
      Nielsen O, Brauer M, Loomis D. 2015. Lung cancer and exposure to nitrogen dioxide
      and traffic: a systematic review and meta-analysis. Environ Health Perspect
      123:1107-1112; http://dx.doi.org/10.1289/ehp.1408882.

PMID- 25870977
TI  - Tetracoordinate silicon complexes of 1,2-bis(indol-2-yl)benzene as blue-emitting
      dyes in the solid state.
AB  - 1,2-Bis(indol-2-yl)benzene was prepared and found to serve as an effective
      bidentate ligand to form stable silicon complexes bearing two N-Si bonds. These
      complexes take boat-shaped 2,7-diaza-1-silepin structures, which undergo a
      butterfly-like conformational motion whose activation barriers were determined by
      shape analysis of variable-temperature (1)H NMR spectra. These silicon complexes
      exhibit blue emissions in solution and in the solid-state with high efficiency. 

PMID- 25870976
TI  - Apoptosis and frequency of total and effector CD8+ T lymphocytes from cutaneous
      leishmaniasis patients during antimonial therapy.
AB  - BACKGROUND: Leishmaniasis is an important parasitic disease affecting millions
      worldwide. Human cutaneous leishmaniasis (CL) is endemic in Rio de Janeiro,
      Brazil, where is caused by Leishmania braziliensis. The adaptive immune response
      is accountable for the healing of CL and despite of key role of CD8+ T cells in
      this immune response little is known about the CD8+ T lymphocytes frequencies,
      apoptosis and antigen-responsive CD8+ T lymphocytes of CL patients during
      antimonial therapy. METHODS: Using flow cytometry, we examined total and effector
      CD8+ T cells from CL patients before (PBT), during (PDT) and after (PAT)
      treatment for apoptosis and frequencies upon isolation and after in vitro L.
      braziliensis antigens (LbAg)-stimulation culture. Besides, a correlation study
      between immunological findings and lesion size was done. RESULTS: PDT showed
      lower frequencies of total CD8+ T lymphocytes and higher levels of apoptosis of
      these cells, which were also observed following LbAg-stimulation culture.
      Regarding effector CD8+ T cells, high frequencies were observed in PDT, while
      lower frequencies were observed in PAT. Interestingly, PDT showed higher
      frequencies of apoptotic-effector CD8+ T lymphocytes. Similar results were seen
      after in vitro antigenic-stimulation assays. Correlation analysis showed that the
      greater the size of lesion, the smaller the frequency of effector CD8+ T
      lymphocytes in PDT and PAT, as well as a positive correlation between apoptotic
      effector CD8+ T cells frequency and lesion size of PDT. CONCLUSIONS: Changes in
      effector CD8+ T-lymphocyte frequencies, during and after treatment, seem to
      represent a critical stage to generate an efficient immune response and suggest
      that these cells would be evolved in the triggering or in the resolution of
      lesion, under the influence of therapy. This hypothesis opens new perspectives to
      clarify controversial statements about the protective or deleterious role of CD8+
      T cells in the cure or aggravation of CL and the new approach of evaluating
      patients during treatment proved to be of utmost importance for understanding the
      immune response in the healing process of human CL.

PMID- 25870978
TI  - A method for selecting structure-switching aptamers applied to a colorimetric
      gold nanoparticle assay.
AB  - Small molecules provide rich targets for biosensing applications due to their
      physiological implications as biomarkers of various aspects of human health and
      performance. Nucleic acid aptamers have been increasingly applied as recognition
      elements on biosensor platforms, but selecting aptamers toward small molecule
      targets requires special design considerations. This work describes modification
      and critical steps of a method designed to select structure-switching aptamers to
      small molecule targets. Binding sequences from a DNA library hybridized to
      complementary DNA capture probes on magnetic beads are separated from nonbinders
      via a target-induced change in conformation. This method is advantageous because
      sequences binding the support matrix (beads) will not be further amplified, and
      it does not require immobilization of the target molecule. However, the melting
      temperature of the capture probe and library is kept at or slightly above RT,
      such that sequences that dehybridize based on thermodynamics will also be present
      in the supernatant solution. This effectively limits the partitioning efficiency
      (ability to separate target binding sequences from nonbinders), and therefore
      many selection rounds will be required to remove background sequences. The
      reported method differs from previous structure-switching aptamer selections due
      to implementation of negative selection steps, simplified enrichment monitoring,
      and extension of the length of the capture probe following selection enrichment
      to provide enhanced stringency. The selected structure-switching aptamers are
      advantageous in a gold nanoparticle assay platform that reports the presence of a
      target molecule by the conformational change of the aptamer. The gold
      nanoparticle assay was applied because it provides a simple, rapid colorimetric
      readout that is beneficial in a clinical or deployed environment. Design and
      optimization considerations are presented for the assay as proof-of-principle
      work in buffer to provide a foundation for further extension of the work toward
      small molecule biosensing in physiological fluids. 

PMID- 25870979
TI  - Prognostic factors and survival rate of osteosarcoma: A single-institution study.
AB  - AIM: Osteosarcoma is a highly malignant primary bone tumor. The study aim to
      evaluate the prognostic factors influencing the survival rate in our center.
      METHODS: This was a retrospective cohort study of all patients treated between
      January 2005 and December 2010. RESULTS: We included 163 patients with an age
      range of 6-59 years (median = 19). The median follow-up was 47 months (range 36
      84). The overall survival in patients who completed chemotherapy and surgery (n =
      117) was 72% at 2 years and 44% at 5 years. Histologically, 99 (85%) had
      osteoblastic, 6 (5%) had chondroblastic and 3 (2.5%) had telangiectatic
      osteosarcoma. Limb salvage surgery was performed in 80 (49%) and 41 (25%)
      underwent amputation. However, 46 patients (28%) underwent no surgical
      intervention and incomplete chemotherapy. In total, 38/79 patients had a good
      chemotherapy response. There was a significantly better survival rate for limb
      salvage versus amputation. Independent prognostic factors for survival are
      compliance to treatment and presence of lung metastasis. CONCLUSION: The overall
      survival of osteosarcoma patients was influenced by the presence of pulmonary
      metastases and compliance to treatment. Histological subtype, different
      chemotherapy regimens and histological necrosis after chemotherapy did not
      significantly influence survival. The patients who did not complete treatment had
      significantly poorer survival.

PMID- 25870980
TI  - Gene-Gene Interplay and Gene-Diet Interactions Involving the MTNR1B rs10830963
      Variant with Body Weight Loss.
AB  - BACKGROUND/AIMS: Investigation of the genetic makeup may facilitate the
      implementation of more personalized nutritional interventions. The aims were to
      examine whether the rs10830963 MTNR1B polymorphism affects weight loss in
      response to a hypocaloric diet and to find potential gene-gene interplays and
      gene-diet interactions. METHODS: 167 subjects enrolled in a personalized
      nutritional intervention for weight loss (3-6 weeks) were examined for
      anthropometric measurements, dietary habits and physical activity at baseline and
      at the first follow-up visit. Three polymorphisms, which have previously been
      associated with body weight regulation, rs10830963 (MTNR1B), rs9939609 (FTO) and
      rs17782313 (MC4R), were analyzed using the Luminex(r) 100/200TM System. RESULTS:
      After adjusting for covariates, females with the rs10830963 CG/GG genotype showed
      lower weight loss than those with the CC genotype. In the total population,
      carriers of variant alleles of both FTO and MC4R showed a significant association
      with MTNR1B and weight loss outcome. Moreover, among women, higher total protein
      and animal protein intakes were associated with a lower weight loss in G allele
      carriers of the MTNR1B variant. CONCLUSIONS: Our data evidenced that rs10830963
      MTNR1B polymorphism could be associated with individual differences in weight
      loss induced by a hypocaloric diet. This association was influenced by FTO and
      MC4R loci and modified by baseline protein intake.

PMID- 25870981
TI  - Effects of syndemics on HIV viral load and medication adherence in the
      multicentre AIDS cohort study.
AB  - OBJECTIVES: The objective of this study is to determine associations between
      intertwining epidemics (syndemics) and HIV medication adherence and viral load
      levels among HIV-positive MSM and to test whether adherence mediates the
      relationship between syndemics and viral load. DESIGN: We analysed participant
      data collected between 2003 and 2009 from the Multicenter AIDS Cohort Study, a
      prospective HIV/AIDS cohort study in four U.S. cities. METHODS: We conducted
      longitudinal analyses (repeated measures mixed models) to assess whether
      differences in viral load levels, undetectable viral load and self-reported HIV
      medication adherence were associated with count of syndemic conditions (substance
      use, depression symptoms and sexual risk behaviour, range 0-3), adjusting for
      race/ethnicity, age and income. Mediation analyses were conducted using
      structural equation modelling and the SAS %mediate macro. RESULTS: Syndemics
      count was associated with higher viral loads (P < 0.0001) and lower adherence (P
      < 0.0001). Increased counts of concomitant syndemics were associated with viral
      load (P < 0.01), detectable viral load (P < 0.05) and adherence (P < 0.001).
      Black MSM experienced worse outcomes across domains than white MSM (P < 0.0001)
      and experienced higher overall rates of syndemics (P < 0.01). Adherence
      significantly mediated the relationship between syndemics and viral load,
      accounting for an estimated 32.3% of the effect (P < 0.05). CONCLUSION:
      Effectively lowering viral load levels among MSM has implications for both
      HIV/AIDS prevention and care. Our findings suggest that integrating substance use
      interventions, mental healthcare and sexual risk prevention into standard HIV
      care may be necessary to optimize treatment and Treatment as Prevention (TasP)
      models.

PMID- 25870983
TI  - Inferring HIV incidence from case surveillance with CD4+ cell counts.
AB  - BACKGROUND: In some countries, HIV surveillance is based on case-reporting of
      newly diagnosed infections. We present a new back-projection method for
      estimating HIV-incidence trends using individuals' CD4 cell counts at diagnosis.
      METHODS: On the basis of a review of CD4 cell count distributions among HIV
      uninfected people, CD4 cell count following primary infection, and rates of CD4
      cell count decline over time among people with HIV, we simulate the expected
      distribution in time between infection and diagnosis. Applying this to all
      diagnosed individuals provides a distribution of likely infection times and
      estimates for population incidence, level of undiagnosed HIV, and the average
      time from infection to diagnosis each year. We applied this method to the
      national HIV case surveillance data of Australia for 1983-2013. RESULTS: The
      estimated number of new HIV infections in Australia in 2013 was 912 (95%
      uncertainty bound 835-1002). We estimate that 2280 (95% uncertainty bound 1900
      2830) people were living with undiagnosed HIV at the end of 2013, corresponding
      to approximately 9.4% (95% uncertainty bound 7.8-10.1%) of all people living with
      HIV. With increases in the average CD4 count at diagnosis, the inferred HIV
      testing rate has been increasing over time and the estimated mean and median
      times between infection and diagnosis have decreased substantially. However, the
      estimated mean time between infection and diagnosis is considerably greater than
      the median, indicating that some people remain undiagnosed for long periods.
      Differences were found between cases attributable to male homosexual exposure
      versus other cases. CONCLUSION: This methodology provides a novel way of
      estimating population incidence by combining diagnosis dates and CD4 cell counts
      at diagnosis.

PMID- 25870982
TI  - Cost-effectiveness of first-line antiretroviral therapy for HIV-infected African
      children less than 3 years of age.
AB  - BACKGROUND: The International Maternal, Pediatric, and Adolescent Clinical Trials
      P1060 trial demonstrated superior outcomes for HIV-infected children less than 3
      years old initiating antiretroviral therapy (ART) with lopinavir/ritonavir
      compared to nevirapine, but lopinavir/ritonavir is four-fold costlier.
      DESIGN/METHODS: We used the Cost-Effectiveness of Preventing AIDS Complications
      (CEPAC)-Pediatric model, with published and P1060 data, to project outcomes under
      three strategies: no ART; first-line nevirapine (with second-line
      lopinavir/ritonavir); and first-line lopinavir/ritonavir (second-line
      nevirapine). The base-case examined South African children initiating ART at age
      12 months; sensitivity analyses varied all key model parameters. Outcomes
      included life expectancy, lifetime costs, and incremental cost-effectiveness
      ratios [ICERs; dollars/year of life saved ($/YLS)]. We considered interventions
      with ICERs less than 1* per-capita gross domestic product (South Africa:
      $7500)/YLS as 'very cost-effective,' interventions with ICERs below 3* gross
      domestic product/YLS as 'cost-effective,' and interventions leading to longer
      life expectancy and lower lifetime costs as 'cost-saving'. RESULTS: Projected
      life expectancy was 2.8 years with no ART. Both ART regimens markedly improved
      life expectancy and were very cost-effective, compared to no ART. First-line
      lopinavir/ritonavir led to longer life expectancy (28.8 years) and lower lifetime
      costs ($41 350/person, from lower second-line costs) than first-line nevirapine
      (27.6 years, $44 030). First-line lopinavir/ritonavir remained cost-saving or
      very cost-effective compared to first-line nevirapine unless: liquid
      lopinavir/ritonavir led to two-fold higher virologic failure rates or 15-fold
      greater costs than in the base-case, or second-line ART following first-line
      lopinavir/ritonavir was very ineffective. CONCLUSIONS: On the basis of P1060
      data, first-line lopinavir/ritonavir leads to longer life expectancy and is cost
      saving or very cost-effective compared to first-line nevirapine. This supports
      WHO guidelines, but increasing access to pediatric ART is critical regardless of
      the regimen used.

PMID- 25870985
TI  - Association of HIV, hepatitis C virus and liver fibrosis severity with
      interleukin-6 and C-reactive protein levels.
AB  - BACKGROUND: Hepatitis C virus (HCV) infection is associated with chronic
      inflammation; yet studies show greater interleukin (IL)-6, but lower C-reactive
      protein (CRP) levels. We determined whether liver fibrosis severity and HCV
      replication affect the ability of IL-6 to stimulate the production of CRP from
      the liver. METHODS: We used multivariable generalized linear regression to
      examine the association of HIV, HCV and transient elastography-measured liver
      stiffness with IL-6 and CRP in participants (164 HIV-monoinfected; 10 HCV
      monoinfected; 73 HIV/HCV-coinfected; 59 neither infection) of the Women's
      Interagency HIV Study. Significant fibrosis was defined as liver stiffness
      greater than 7.1 kPa. RESULTS: IL-6 was positively correlated with CRP levels in
      all women, but CRP levels were lower in HCV-infected women (with and without HIV
      infection) at all levels of IL-6. HCV-infected women with fibrosis had nearly 2.7
      fold higher IL-6 levels compared to controls [95% confidence interval (CI 146%,
      447%]; HCV-infected women without fibrosis had IL-6 levels that were similar to
      controls. By contrast, CRP was 28% lower in HCV-infected women with fibrosis (95%
      CI -55%, 15%) and 47% lower in HCV-infected women without fibrosis (95% CI -68%, 
      12%). Among the HCV-infected women, higher HCV-RNA levels were associated with 9%
      lower CRP levels per doubling (95% CI -18%, 0%). CONCLUSION: Liver fibrosis
      severity is associated with greater IL-6 levels, but the stimulatory effect of IL
      6 on CRP appears to be blunted by HCV replication rather than by liver fibrosis
      severity. Investigation of the potential CRP rebound after HCV-RNA eradication
      and persistent liver fibrosis on organ injury is needed.

PMID- 25870987
TI  - Concurrency can drive an HIV epidemic by moving R0 across the epidemic threshold.
AB  - OBJECTIVE: The objective of this study is to investigate whether concurrency can
      drive an HIV epidemic by moving R0 across the epidemic threshold. DESIGN AND
      METHODS: We use a mathematical framework for a dynamic partnership network and
      the spread of a one-stage infection to study how concurrency is related to the
      basic reproduction number R0. Two concurrency indices were used to measure the
      level of concurrency. The model allows varying the level of concurrency in the
      population, while other key network properties such as partnership duration and
      lifetime number of partners are kept fixed. In this way, the effect of
      concurrency on R0 is investigated as an isolated phenomenon. RESULTS: We find
      that an increase in concurrency is associated with an increase of R0. For
      plausible parameter sets for MSM populations, R0 is always above the epidemic
      threshold of 1. For scenarios that are plausible for sub-Saharan African
      populations, we show that increasing the level of concurrency can lead to R0
      crossing the epidemic threshold. This occurs already at low levels of
      concurrency. Only a slight shift of the network structure from a purely
      monogamous population to one wherein individuals are allowed to have at most two
      partners is enough for this to happen. CONCLUSION: Concurrency can be a driver of
      an HIV epidemic in sub-Saharan Africa for low levels of concurrency, although it
      is not decisive in MSM populations. A small increase in the level of concurrency
      can lead to R0 crossing the epidemic threshold in a sub-Saharan African setting.

PMID- 25870984
TI  - Liver-related death among HIV/hepatitis C virus-co-infected individuals:
      implications for the era of directly acting antivirals.
AB  - BACKGROUND: Potent, less toxic, directly acting antivirals (DAAs) for treatment
      of hepatitis C virus (HCV) infection promise to improve HCV cure rates among
      HIV/HCV-co-infected individuals. However, the costs of treatment will necessitate
      prioritization of those at greatest risk of liver-related death (LRD) for
      therapy. This study aims to provide guidance on who should be prioritized for DAA
      treatment. METHODS: Three thousand, nine hundred and forty-one HCV antibody
      positive PSHREG and FIB-4 are names not acronyms (EuroSIDA) patients with follow
      up after 1 January 2000 were included, with causes of death classified using
      Coding causes of Death in HIV (CoDe) methodology. Crude death rates, competing
      risks Cox proportional-hazards models and cumulative incidence functions were
      used to describe factors associated with LRD. RESULTS: LRD accounted for 145 of
      670 (21.6%) deaths in the study population. LRD rates peaked in those aged 35-45
      years, and occurred almost exclusively in those with at least F2 fibrosis at
      baseline. In adjusted Cox models, risk factors for LRD included F4 or F2/F3
      fibrosis [sub-distribution hazard ratio (sHR) 6.3, 95% confidence interval (CI)
      4.1-9.6; and sHR 2.5, 95% CI 1.5-4.2 vs. F0/F1, respectively), CD4 cell count
      (sHR 0.83, 95% CI 0.73-0.95 per doubling) and hepatitis B surface antigen
      positive (sHR 2.2, 95% CI 1.3-3.5 vs. hepatitis B surface antigen-negative). The
      5-year probability of LRD was low in those with F0/F1 fibrosis (sHR 2.2%, 95% CI
      1.7-2.9), but substantial in those with F2/F3 and F4 fibrosis (sHR 10.3%, 95% CI
      7.6-13.5; and sHR 14.0%, 95% CI 10.3-18.3, respectively). CONCLUSION: Treatment
      with DAAs should be prioritized for those with at least F2 fibrosis. Early
      initiation of cART with the aim of avoiding low CD4 cell counts should be
      considered essential to decrease the risk of LRD and the need for HCV treatment.

PMID- 25870986
TI  - The effect of short-course antiretroviral therapy initiated in primary HIV-1
      infection on interleukin-6 and D-dimer levels.
AB  - OBJECTIVE: Interruption of antiretroviral therapy (ART) in chronic HIV disease is
      associated with increased mortality, predicted by elevations in interleukin-6 (IL
      6) and D-dimer. The effect of ART interruption in primary HIV-1 infection on
      these biomarkers is unknown. METHODS: Plasma samples from 200 HIV seroconverters
      enrolled in the Short Pulse Anti-Retroviral Therapy At HIV Seroconversion trial
      of deferred ART (standard of care) - 12 or 48 week ART (ART12 or ART48,
      respectively) - were analysed for IL-6 and D-dimer at weeks 0, 12, 16, 48, 52, 60
      and 108 after randomization. Changes in log10 levels from weeks 0 to 12 were
      analysed using linear regression, as were changes from baseline to 4 weeks after
      stopping ART. Areas under the biomarker-time curves (AUC) to week 108 were
      adjusted for baseline values, and compared across all arms. RESULTS: Median
      (inter-quartile range) baseline IL-6 and D-dimer were 1.45 (0.88, 2.41) pg/ml and
      0.34 (0.20, 0.50) mg/l, respectively. At week 12, D-dimer levels were
      significantly lower among treated compared to untreated individuals (P < 0.001),
      whereas IL-6 levels were similar (P = 0.23). Within 4 weeks from stopping ART, IL
      6 and D-dimer levels rose by 22 and 18%, reaching pre-ART levels. Over 108-week
      follow-up, there was no difference between arms in IL-6 AUC (P = 0.53), but D
      dimer AUC was significantly lower for ART12 and ART48 compared to standard of
      care (overall P = 0.008). CONCLUSION: Stopping ART in primary HIV-1 infection
      leads to inflammatory biomarker rebound to pre-treatment levels. However, over
      108-week follow-up, we found no evidence that biomarker levels were higher for
      those interrupting ART, compared to those remaining ART-naive, and D-dimer levels
      were significantly lower.

PMID- 25870988
TI  - Young age at start of antiretroviral therapy and negative HIV antibody results in
      HIV-infected children when suppressed.
AB  - BACKGROUND: Negative results on standard HIV antibody tests have been described
      among HIV-infected children suppressed on antiretroviral therapy (ART) started
      early in life. Here, we describe the frequency and predictors of this phenomenon
      in a well characterized cohort of treated children. METHODS: We selected samples
      from 103 HIV-infected children who started ART 14 months of age or less and from
      122 children who started 6 months of age or less followed as part of two
      sequential clinical trials in Johannesburg, South Africa. Children had attained
      viral suppression on ART and had received ART for between 3 and 6.4 years (mean
      4.3 years) when tested for HIV antibody using a standard ELISA (Genescreen HIV1/2
      version 2; Bio-rad). RESULTS: Only children 6 months of age or less when ART was
      started had negative antibody results when tested after suppression on ART
      several years later. Negative or low-positive antibody results were observed in
      40.0, 37.0 and 27.8% of children starting ART less than 2 months of age, or
      starting during month 2 or 3, respectively. This dropped to 5.9, 3.5 and 5.3% if
      ART was started during month 4, 5 and 6, respectively. Higher CD4 percentage
      prior to ART initiation and no recorded intermittent viremia also predicted
      negative antibody results. CONCLUSION: Testing negative on standard HIV antibody
      tests occurs fairly commonly among HIV-infected children who started ART 3 months
      of age or less and are virally suppressed. It would be prudent in clinical
      practice to avoid HIV antibody tests among virally suppressed, early-treated
      children to prevent unnecessary confusion.

PMID- 25870989
TI  - The need for treatment interruption studies and biomarker identification in the
      search for an HIV cure.

PMID- 25870990
TI  - The histone deacetylase inhibitor panobinostat lowers biomarkers of
      cardiovascular risk and inflammation in HIV patients.
AB  - OBJECTIVE: To investigate the effect of the histone deacetylase inhibitor
      panobinostat on HIV-associated inflammation. DESIGN: Sub-study of a single-arm,
      phase I/II clinical trial. METHODS: HIV-infected adults on suppressive
      antiretroviral therapy received oral panobinostat 20 mg three times per week,
      every other week, for 8 weeks, that is, four cycles of treatment. Plasma levels
      of high-sensitivity C-reactive protein, matrix metalloproteinase 9, soluble CD40
      ligand and interleukin-6 were determined using human ELISA kits. Soluble
      endothelia selectin (E-selectin) was measured by a multiplex immunoassay. Total
      monocyte count, phenotype changes on monocytes and monocyte histone acetylation
      were analyzed using flow cytometry. Whole-genome expression in peripheral blood
      mononuclear cells was analyzed at baseline and on-panobinostat employing the
      Affymetrix Human Transcriptome Array 2.0 microarray assay. Changes from baseline
      were analyzed using Wilcoxon signed-rank test. For the gene-expression analyses,
      fold-changes, P values and false detection rate were computed using TAC software.
      RESULTS: Panobinostat treatment led to significant reductions in multiple
      established plasma markers of inflammation. Notably, high-sensitivity C-reactive
      protein decreased by a median of 58% during treatment and this change persisted
      for 4 weeks after treatment. Plasma levels of interleukin-6, matrix
      metalloproteinase 9, E-selectin and soluble CD40 ligand also significantly
      decreased on and/or postpanobinostat. Additionally, we observed a significant
      reduction in the proportions of intermediate monocytes and tissue factor-positive
      monocytes. This suppression of cardiovascular risk biomarkers was associated with
      a prominent reduction in the expression of genes related to inflammation and
      atherosclerosis. CONCLUSION: Collectively, these data indicate that panobinostat
      may have therapeutic potential to target excess inflammation in HIV patients with
      high cardiovascular risk.

PMID- 25870992
TI  - Two recent studies find Depo-Provera use increases HIV risk.

PMID- 25870991
TI  - Impact of protease inhibitors on intracellular concentration of tenofovir
      diphosphate among HIV-1 infected patients.
AB  - Intracellular nucleoside reverse transcriptase inhibitor (NRTI) concentrations
      are associated with plasma HIV-1 response. Coadministration of protease
      inhibitors with NRTIs can affect intracellular concentrations due to protease
      inhibitor inhibition of efflux transporters. Tenofovir-diphosphate (TFV-DP)
      concentrations within peripheral blood mononuclear cells were compared among
      individuals receiving either atazanavir or darunavir-based regimens. There was a
      trend towards higher TFV-DP concentrations among women and among participants
      receiving atazanavir. TFV-DP intracellular concentrations were positively
      associated with undetectable plasma HIV-1 RNA. 

PMID- 25870993
TI  - HIV-infected adults experience accentuated but not accelerated ageing.

PMID- 25870994
TI  - Effect of selenium supplementation on CD4+ T-cell recovery, viral suppression and
      morbidity of HIV-infected patients in Rwanda: a randomized controlled trial.
AB  - OBJECTIVE: To examine the effect of selenium supplementation on CD4 T-cell
      counts, viral suppression, and time to antiretroviral therapy (ART) initiation in
      ART-naive HIV-infected patients in Rwanda. METHODS: A multicenter, double
      blinded, placebo-controlled, randomized clinical trial was conducted. Eligible
      patients were HIV-infected adults (>=21 years) who had a CD4 cell count between
      400 and 650 cells/MUl (ART eligibility was <=350 cells/MUl throughout the trial),
      and were willing to practice barrier methods of birth control. Patients were
      randomized to receive once-daily 200 MUg selenium tablets or identical placebo.
      They were followed for 24 months with assessments every 6 months. Declines in CD4
      cell counts were modeled using linear regressions with generalized estimating
      equations and effect modification, and the composite outcome (ART eligible or ART
      initiation) using Cox proportional-hazards regression, both conducted with
      intention to treat. RESULTS: Of the 300 participants, 149 received selenium, 202
      (67%) were women, and median age was 33.5 years. The rate of CD4 depletion was
      reduced by 43.8% [95% confidence interval (CI) 7.8-79.8% decrease] in the
      treatment arm - from mean 3.97 cells/MUl per month to mean 2.23 cells/MUl per
      month. We observed 96 composite outcome events - 45 (47%) in the treatment arm.
      We found no treatment effect for the composite outcome (hazard ratio 1.00, 95% CI
      0.66-1.54) or viral suppression (odds ratio 1.18, 95% CI 0.71-1.94). The trial
      was underpowered for the composite outcome due to a lower-than-anticipated event
      rate. Adverse events were comparable throughout. CONCLUSIONS: This randomized
      clinical trial demonstrated that 24-month selenium supplementation significantly
      reduces the rate of CD4 cell count decline among ART-naive patients.

PMID- 25870996
TI  - Depressive symptoms at discharge from rehabilitation predict future
      cardiovascular-related hospitalizations.
AB  - OBJECTIVES: Depression is associated with poor prognosis in patients with
      cardiovascular disease (CVD). We hypothesized that depressive symptoms at
      discharge from a cardiac rehabilitation program are associated with an increased
      risk of future CVD-related hospitalizations. METHODS: We examined 486 CVD
      patients (mean age=59.8+/-11.2) who enrolled in a comprehensive 3-month
      rehabilitation program and completed the depression subscale of the Hospital
      Anxiety and Depression Scale (HADS-D). At follow-up we evaluated the predictive
      value of depressive symptoms for CVD-related hospitalizations, controlling for
      sociodemographic factors, cardiovascular risk factors, and disease severity.
      RESULTS: During a mean follow-up of 41.5+/-15.6 months, 63 patients experienced a
      CVD-related hospitalization. The percentage of depressive patients (HADS-D>=8)
      decreased from 16.9% at rehabilitation entry to 10.7% at discharge. Depressive
      symptoms at discharge from rehabilitation were a significant predictor of outcome
      (HR 1.32, 95% CI 1.09-1.60; p=0.004). Patients with clinically relevant
      depressive symptoms at discharge had a 2.5-fold increased relative risk of poor
      cardiac prognosis compared to patients without clinically relevant depressive
      symptoms independently of other prognostic variables. CONCLUSION: In patients
      with CVD, depressive symptoms at discharge from rehabilitation indicated a poor
      cardiac prognosis.

PMID- 25870995
TI  - A comparative phase 1 clinical trial to identify anti-infective mechanisms of
      vitamin D in people with HIV infection.
AB  - OBJECTIVES: To determine if there is a biological mechanism that explains the
      association between HIV disease progression and increased mortality with low
      circulating vitamin D levels; specifically, to determine if restoring vitamin D
      levels induced T-cell functional changes important for antiviral immunity.
      DESIGN: This was a pilot, open-label, three-arm prospective phase 1 study.
      METHODS: We recruited 28 patients with low plasma vitamin D (<50 nmol/l 25
      hydroxyvitamin D3), comprising 17 HIV+ patients (11 on HAART, six treatment
      naive) and 11 healthy controls, who received a single dose of 200 000 IU oral
      cholecalciferol. Advanced T-cell flow cytometry methods measured CD4 T-cell
      function associated with viral control in blood samples at baseline and 1-month
      after vitamin D supplementation. RESULTS: One month of vitamin D supplementation
      restored plasma levels to sufficiency (>75 nmol/l) in 27 of 28 patients, with no
      safety issues. The most striking change was in HIV+ HAART+ patients, where
      increased frequencies of antigen-specific T cells expressing macrophage
      inflammatory protein (MIP)-1beta - an important anti-HIV blocking chemokine -
      were observed, with a concomitant increase in plasma MIP-1beta, both of which
      correlated significantly with vitamin D levels. In addition, plasma cathelicidin 
      a vitamin D response gene with broad antimicrobial activity - was enhanced.
      CONCLUSION: Vitamin D supplementation modulates disease-relevant T-cell functions
      in HIV-infected patients, and may represent a useful adjunct to HAART therapy.

PMID- 25870997
TI  - The effect of polymer solubilizing side-chains on solar cell stability.
AB  - The impact of side-chain variations on the photothermal stability of solar cells
      containing poly(benzodithiophene-diketopyrrolopyrrole) polymers are investigated
      in the absence of oxygen. Four different side-chains of benzodithiophene (BDT)
      are synthesized and copolymerized with diketopyrrolopyrrole (DPP) by Stille
      polymerization. The photothermal stability is measured as active layer blends
      with phenyl-C61-butyric acid methyl ester (PCBM) in encapsulated inverted
      photovoltaic cell architecture with zinc oxide and PEDOT: PSS as transport layers
      (ITO/ZnO/active layer/ PEDOT: PSS/Ag). Device degradation is correlated to the
      morphological behavior of the polymer:blend upon AM1.5 illumination (UV-visible
      light, 50  degrees C) and have been investigated by AFM, XRD, and UV-Vis. Once
      exposed to the light and to the temperature the BHJ stability is governed by two
      processes (i) PCBM crystallization and (ii) PCBM dimerization. Dimerization
      results in a rapid initial performance decrease followed by a more gradual
      decrease caused by a slower thermally activated crystallization. Depending on the
      blend morphology, dictated by the polymer's alkyl chain, the two processes occur
      to different extents thereby modulating the BHJ stability. Thus, of the polymer
      side-chains explored, linear alkyl side-chains stabilized the bulk heterojunction
      most effectively followed by no side-chain, alkoxy and branched side-chains.
      Lowering the concentration of fullerene in the active layer also reduces the rate
      of degradation across the polymers tested. This is a result of both the rate of
      crystallization and dimerization of fullerene being dependent on its
      concentration and the nature of the polymer side-chains. This approach appears to
      be a general strategy to increase the polymer:PCBM stability.

PMID- 25870998
TI  - Monopolar versus PlasmakineticTM Energy Effect on Prostatic Tissue Damage in
      Terms of PSA Levels: A Prospective Randomized Trial.
AB  - INTRODUCTION: We investigated the monopolar and bipolar energy effects on
      prostate and correlated the results with the type of pathology, thus determining
      the relationship between tissue damage and the PSA level. MATERIAL AND METHODS:
      One hundred and twenty four patients underwent TURP and according to the energy
      source, 2 groups were designed as monopolar (Group 1) and bipolar energy (Group
      2). Hemoglobin and free and total PSA were measured preoperatively and 6 hours
      postoperatively, and differences were calculated. The weight of resected tissue
      and operation time were also recorded. Two groups were also formed later
      according to the pathology as chronic prostatitis (CP) and BPH. The findings were
      analyzed. RESULTS: There were no statistical differences between the groups in
      terms of age; prostate volumes; resected tissue; operation times; pre- and
      postoperative Hb, total-free PSA, IPSS, PVR, and quality of life scores; or
      postoperative maximum flow rates. Changes in total-free PSA (25.7 and 10.8 ng/dl
      for PSA; 13.2 and 5.76 ng/dl for free PSA for Groups 1 and 2, respectively) were
      significantly different between Groups 1 and 2. There was a statistical
      difference in total PSA between the groups among CP patients (28.18 and 11.73
      ng/dl for Groups 1 and 2, respectively). But no statistical difference existed
      among BPH patients. The change in Hb differed based on pathological results.
      CONCLUSION: Bipolar TURP is less invasive than monopolar TURP on the basis of
      postoperative PSA levels. In addition, bleeding during TURP is affected not by
      the kind of energy, but by the pathology.

PMID- 25870999
TI  - Secreted IL-1alpha promotes T-cell activation and expansion of CD11b(+) Gr1(+)
      cells in carbon tetrachloride-induced liver injury in mice.
AB  - Interleukin-1alpha is mainly expressed on the cell membrane, but can also be
      secreted during inflammation. The roles of secreted and membrane IL-1alpha in
      acute liver inflammation are still not known. Here, we examined the functions of
      secreted and membrane IL-1alpha in a mouse model of carbon tetrachloride-induced
      acute liver injury. We show that secreted IL-1alpha aggravates liver damage and
      membrane IL-1alpha slightly protects mice from liver injury. Further studies
      showed that secreted IL-1alpha promotes T-cell activation. It also increased the
      expansion of CD11b(+) Gr1(+) myeloid cells, which may serve as a negative
      regulator of acute liver inflammation. Moreover, secreted IL-1alpha induced IL-6
      production from hepatocytes. IL-6 neutralization reduced the proliferation of
      CD11b(+) Gr1(+) myeloid cells in vivo. CCL2 and CXCL5 expression was increased by
      secreted IL-1alpha in vitro and in vivo. Antagonists of the chemokine receptors
      for CCL2 and CXCL5 significantly reduced the migration of CD11b(+) Gr1(+) myeloid
      cells. These results demonstrate that secreted and membrane IL-1alpha play
      different roles in acute liver injury. Secreted IL-1alpha could promote T-cell
      activation and the recruitment and expansion of CD11b(+) Gr1(+) myeloid cells
      through induction of CCL2, CXCL5, and IL-6. The controlled release of IL-1alpha
      could be a critical regulator during acute liver inflammation.

PMID- 25871000
TI  - Letters to the editor.

PMID- 25871001
TI  - Pelvic organ prolapse: a consequence of nature or nurture?

PMID- 25871002
TI  - Equalizing equol for hot flash relief? Still more questions than answers.

PMID- 25871003
TI  - Timing of menopausal hormone therapy and myocardial infarction.

PMID- 25871004
TI  - Polymorphisms in neuropeptide genes and bone mineral density in Korean
      postmenopausal women.
AB  - OBJECTIVE: The purpose of this study was to investigate the association between
      single nucleotide polymorphisms in neuropeptide genes and bone mineral density
      (BMD) in Korean postmenopausal women. METHODS: Twenty polymorphisms in NMU
      (neuromedin U; two polymorphisms), NMU2R (NMU receptor 2; six polymorphisms),
      CART (cocaine- and amphetamine-regulated transcript; three polymorphisms), NPY
      (neuropeptide Y; four polymorphisms), NPY2R (NPY type 2 receptor; two
      polymorphisms), NOS1 (neuronal nitric oxide synthase; two polymorphisms), and
      MC4R (melanocortin 4 receptor; one polymorphism) genes were analyzed in 482
      Korean postmenopausal women. BMD at the lumbar spine and femoral neck was also
      examined. Effects of polymorphisms on BMD were evaluated after adjusting for
      potential confounding factors using analysis of covariance. Odds ratios and 95%
      CIs for osteoporosis were estimated using chi2 test or Fisher's exact test.
      RESULTS: Among the polymorphisms measured, the AG genotype of CART rs2239670 had
      the highest BMD at the lumbar spine. Furthermore, osteoporosis at the lumbar
      spine was more frequently observed in the GG genotype of NPY rs17149106
      polymorphism and in the CC genotype of NPY rs16123 polymorphism and was less
      frequently observed in the TT-TT genotype identified by a combined polymorphism
      in the NPY2R gene, compared with the other genotypes. The AA genotype of NOS1
      rs1279104 polymorphism was found to have a 3.68-fold higher prevalence of
      osteoporosis at the femoral neck compared with the GG genotype (95% CI, 1.29
      10.50; P = 0.02). CONCLUSIONS: Results suggest that CART rs2239670 polymorphism
      may be one of the genetic factors affecting lumbar spine BMD in Korean
      postmenopausal women and that NPY rs17149106, NPY rs16123, NOS1 rs1279104, and
      combined (rs2880415 and rs6857715) polymorphisms in the NPY2R gene may be useful
      in identifying women at risk for osteoporosis.

PMID- 25871006
TI  - Letter to the editor.

PMID- 25871005
TI  - Cluster analysis of midlife women's sleep-related symptoms: racial/ethnic
      differences.
AB  - OBJECTIVE: The purpose of this study was to identify clusters of midlife women by
      sleep-related symptoms in multiethnic groups and to examine racial/ethnic
      differences in the clusters. METHODS: This secondary analysis was conducted on
      data from 1,054 midlife women who participated in two cross-sectional descriptive
      national Internet surveys. The instruments included questions on background
      characteristics, health, and menopause status, and the Sleep Index for Midlife
      Women. The data were analyzed using hierarchical clustering methods, chi2 test,
      analysis of variance, and multinomial logistic regression analyses. RESULTS: A
      four-cluster solution was adopted: cluster 1 (low total symptoms group), cluster
      2 (moderate physical and psychosomatic symptoms group), cluster 3 (moderate
      psychological symptoms group), and cluster 4 (high total symptoms group). There
      were significant differences in education, employment status, family income,
      social support, country of birth, race/ethnicity, body mass index, perceived
      general health, diagnosed disease, access to health care, and menopause status
      among clusters (P < 0.05). In cluster 1 only, there were significant
      racial/ethnic differences in the total number of total severity scores for
      physical symptoms (P < 0.01). When racial/ethnic differences in individual
      symptoms in each cluster were determined, there were no consistent racial/ethnic
      differences. CONCLUSIONS: Researchers need to consider that racial/ethnic
      differences could be prominent in midlife women with low sleep-related symptoms.

PMID- 25871008
TI  - Lateral window sinus augmentation: complications and outcomes of 101 consecutive
      procedures.
AB  - PURPOSE: To report the complications experienced and the outcomes of simultaneous
      or staged dental implants placed during 101 consecutive sinus augmentation
      procedures through the lateral window approach. PATIENTS AND METHODS: Sixty-eight
      consecutive patients underwent a total of 101 sinus augmentations. Thirty-nine
      patients were operated on unilaterally and 29 bilaterally. A total of 141
      implants were installed, 65 simultaneously and 76 in a second stage. RESULTS: In
      13 of the 101 sinuses, the Schneiderian membrane was perforated. Three patients
      developed maxillary sinusitis. Two patients suffered perioperative hemorrhages.
      One patient had a wound dehiscence, and 3 patients developed graft infections. Of
      the 141 implants, 121 integrated and 14 failed. There was a statistical
      difference between the losses of implants placed simultaneously versus
      nonsimultaneously (P = 0.003). The overall postloading success rate for dental
      implants reached 90% after a follow-up period between 12 and 120 months.
      CONCLUSION: The lateral window approach is associated with a high rate of
      success. Yet, some complications can influence the outcome of clinical treatment.
      Simultaneous placement of implants during sinus augmentation significantly
      affects their chance of success.

PMID- 25871011
TI  - Mesoscopic simulation of the self-assembly of the weak polyelectrolyte
      poly(ethylene oxide)-block-poly(methyl methacrylate) diblock copolymers.
AB  - We designed twelve types of weak polyelectrolytes (i.e., PEO-b-PMMA copolymers
      (BCP) in multi-arm structures, where six include EO blocks as joint points and
      the other six have MMA blocks as joint points). All of the BCPs with EO as the
      joint points form disordered phases with the exception of long-chained and four
      armed BCP. The main mesophases of all of the BCPs with MMA as joint points are
      micelle-like and bicontinuous phases. In particular, the short-chained BCP with
      four-arms and EO segments outside form a new phase type (i.e., crossed lamellar
      phase). Using MesoDyn, we provide a comprehensive representation of the micelle
      and crossed lamellar phase formation mechanisms based on both thermodynamic and
      dynamic analyses. A shear force on a micelle-like phase could promote a hexagonal
      columnar phase, which is a good technique for generating an ordered arrangement
      of nanotube arrays. Blending homopolymers with the same constituents could
      promote uniformity of the micelle size and decrease the polydispersity,
      especially for blends with a high BCP concentration, which may provide a new
      approach for regulating the properties of materials. 

PMID- 25871010
TI  - Medical smart textiles based on fiber optic technology: an overview.
AB  - The growing interest in the development of smart textiles for medical
      applications is driven by the aim to increase the mobility of patients who need a
      continuous monitoring of such physiological parameters. At the same time, the use
      of fiber optic sensors (FOSs) is gaining large acceptance as an alternative to
      traditional electrical and mechanical sensors for the monitoring of thermal and
      mechanical parameters. The potential impact of FOSs is related to their good
      metrological properties, their small size and their flexibility, as well as to
      their immunity from electromagnetic field. Their main advantage is the
      possibility to use textile based on fiber optic in a magnetic resonance imaging
      environment, where standard electronic sensors cannot be employed. This last
      feature makes FOSs suitable for monitoring biological parameters (e.g.,
      respiratory and heartbeat monitoring) during magnetic resonance procedures.
      Research interest in combining FOSs and textiles into a single structure to
      develop wearable sensors is rapidly growing. In this review we provide an
      overview of the state-of-the-art of textiles, which use FOSs for monitoring of
      mechanical parameters of physiological interest. In particular we briefly
      describe the working principle of FOSs employed in this field and their relevant
      advantages and disadvantages. Also reviewed are their applications for the
      monitoring of mechanical parameters of physiological interest. 

PMID- 25871009
TI  - Epsin is required for Dishevelled stability and Wnt signalling activation in
      colon cancer development.
AB  - Uncontrolled canonical Wnt signalling supports colon epithelial tumour expansion
      and malignant transformation. Understanding the regulatory mechanisms involved is
      crucial for elucidating the pathogenesis of and will provide new therapeutic
      targets for colon cancer. Epsins are ubiquitin-binding adaptor proteins
      upregulated in several human cancers; however, the involvement of epsins in colon
      cancer is unknown. Here we show that loss of intestinal epithelial epsins
      protects against colon cancer by significantly reducing the stability of the
      crucial Wnt signalling effector, dishevelled (Dvl2), and impairing Wnt
      signalling. Consistently, epsins and Dvl2 are correspondingly upregulated in
      colon cancer. Mechanistically, epsin binds Dvl2 via its epsin N-terminal homology
      domain and ubiquitin-interacting motifs and prohibits Dvl2 polyubiquitination and
      degradation. Our findings reveal an unconventional role for epsins in stabilizing
      Dvl2 and potentiating Wnt signalling in colon cancer cells to ensure robust colon
      cancer progression. The pro-carcinogenic role of Epsins suggests that they are
      potential therapeutic targets to combat colon cancer. 

PMID- 25871012
TI  - Design, synthesis, and pharmacological evaluation of highly potent and selective
      dipeptidyl peptidase-4 inhibitors.
AB  - The optimization of a series of fused beta-homophenylalanine inhibitors of
      dipeptidyl peptidase-4 (DPP-4) is described. Modification on the P2-binding
      moiety of 6 (IC50 = 10 nM) led to the discovery of beta-homophenylalanine
      derivatives containing pyrrolidin-2-ylmethyl amides. The introduction of a
      sulfamine in the meta position of the phenyl ring improved the potency against
      DPP-4 (6-12-fold increase). Compound 14k showed DPP-4 inhibitory activity with an
      IC50 value of 0.87 nM. Meanwhile, in vivo experiments exhibited that 14h had an
      efficiency comparable to sitagliptin at the dose of 10 mg/kg.

PMID- 25871014
TI  - Sleep disturbances and related factors among family caregivers of patients with
      advanced cancer.
AB  - OBJECTIVE: Sleep disturbances among family caregivers (FCs) are common in
      advanced cancer. The comprehensive factors for sleep disturbances among the FCs
      of patients with cancer have not been investigated in Taiwan. The purposes of
      this study were to investigate the sleep disturbances among the FCs of patients
      with advanced cancer and to determine predictors of sleep disturbance. METHODS: A
      descriptive, cross-sectional study was conducted among 172 FCs. Data were
      collected using the Pittsburgh Sleep Quality Index and wrist actigraphy. A linear
      regression model was used to identify the predictive factors for sleep quality.
      RESULTS: Seventy-six percent of the FCs experienced some sleep disturbances.
      Female gender, more fatigue, greater depression, more caregiving burden, and
      spending over 16 h per day on caregiving tasks were risk factors for sleep
      disturbances in caregivers. CONCLUSIONS: Sleep disturbances were common among the
      Taiwanese FCs of patients with advanced cancer. FCs with risk factors for sleep
      disturbances should be identified and provided assistance.

PMID- 25871013
TI  - Sequential Immune Responses: The Weapons of Immunity.
AB  - Sequential immune responses (SIR) is a new model that describes what 'immunity'
      means in higher animals. Existing models, such as self/nonself discrimination or
      danger, focus on how immune responses are initiated. However, initiation is not
      protection. SIR describes the actual immune responses that provide protection.
      SIR resulted from a comprehensive analysis of the evolution of immune systems
      that revealed that several very different types of host innate responses occur
      (and at different tempos) which together provide host protection. SIR1 uses
      rapidly activated enzymes like the NADPH oxidases and is present in all animal
      cells. SIR2 is mediated by the first 'immune' cells: macrophage-like cells. SIR3
      evolved in animals like invertebrates and provides enhanced protection through
      advanced macrophage recognition and killing of pathogens and through other innate
      immune cells such as neutrophils. Finally, in vertebrates, macrophages developed
      SIR4: the ability to present antigens to T cells. Though much slower than SIR1-3,
      adaptive responses provide a unique new protection for higher vertebrates.
      Importantly, newer SIR responses were added on top of older, evolutionarily
      conserved functions to provide 'layers' of host protection. SIR transcends
      existing models by elucidating the different weapons of immunity that provide
      host protection in higher animals. 

PMID- 25871015
TI  - Survival analysis and prognosis for patients with serous and mucinous borderline
      ovarian tumors: 14-year experience from a tertiary center in Iran.
AB  - The aim of this study was to determine the prognosis and survival for patients
      with borderlineovarian tumor (BOT). A retrospective review of 30 patients with
      serous andmucinous BOT treated at or referred to our institution was performed.
      Fifteenpatients (50%) had serous, and the others had mucinous BOT. About 86% of
      allpatients in both groups were in stage I of the disease. The recurrent disease
      occurredin 7% and 21% of serous and mucinous tumors, respectively. All
      recurrences,except one in mucinous tumors, were found in advance stage disease.
      After amean of 37 and 52 months follow-up, the overall survival was 100% and 93%,
      anddisease-free survival was 93% and 79% for serous and mucinous
      tumors,respectively. In this series, advanced stage was associated with
      poorprognosis. However, to obtain more accurate information further studies
      withnumber of patients and longer follow-up is recommended. 

PMID- 25871017
TI  - Effects of sesame seed supplementation on inflammatory factors and oxidative
      stress biomarkers in patients with knee osteoarthritis.
AB  - Considering the high prevalence of osteoarthritis (OA) and since until now there
      has not been any human studies to evaluate the effect of sesame in OA patients,
      this study was designed to assess the effect of administration of sesame on
      inflammation and oxidative stress in patients with knee OA. Fifty patients with
      knee OA were allocated into two groups namely control and sesame group. 25
      patients in the control group received 40 g placebo powder per day while 25
      patients in the sesame group received 40 g of sesame seed daily during two months
      of study along with standard medical therapy. Serum total antioxidant capacity,
      malondialdehyde (MDA), high-sensitivity C-reactive protein (hs-CRP) and
      interleukin-6 (IL-6) were measured. In the sesame group, a significant decrease
      in serum MDA and hs-CRP were seen after two months of study (P<0.05). There was
      no significant difference in post-treatment serum values of MDA, TAC and hs-CRP
      between two groups (P>0.05). Serum IL-6 decreased significantly in both groups
      compared with baseline during the two-month study (P<0.05). There was a
      significant difference in mean serum IL-6 between two groups after treatment
      (P=0.001). Sesame seed is a natural and safe substance that may have beneficial
      effects in patients with knee OA, and it may provide new complementary and
      adjunctive treatment in these patients. 

PMID- 25871016
TI  - Olfactory dysfunction in Iranian diabetic patients.
AB  - Olfactory dysfunction is a known complication of diabetes and, despite its
      importance in the quality of life, is usually neglected due to its gradual
      progression. In this study, we aim to determine the prevalence and severity of
      olfactory dysfunction in diabetics and its association with microangiopathic
      complications of the disease (neuropathy, nephropathy, and retinopathy).
      Excluding the confounding factors, a case-control study of 60 eligible subjects,
      divided into a group of 30 diabetic patients and a group of 30 control subjects
      was performed. We used "absorbent perfumer's paper strips" method to test the
      olfactory threshold. In our study, 60% of diabetics were found to have some
      degree of olfactory dysfunction and a significant difference (P<0.01) between the
      olfactory threshold of the case and control groups was observed. There were no
      significant associations between the olfactory dysfunction and age, sex,
      treatment duration and microangiopathic complications. 

PMID- 25871018
TI  - The association between social capital and burnout in nurses of a trauma referral
      teaching hospital.
AB  - Social capital is a multi-faceted phenomenon in social sciences that massively
      affects many social fields. It can be a helpful factor in promoting health. Among
      the groups with high burnout, nurses have always shown higher levels of burnout.
      Studies have revealed that social capital can be an important factor affecting
      burnout. This study aimed to determine the extent of the effect of social capital
      on burnout in nurses of a trauma referral teaching hospital in Rasht. This was a
      descriptive correlational study conducted on 214 nurses of a trauma referral
      teaching hospital. Maslach standard questionnaire and the social capital
      questionnaire devised by Boyas and colleagues were used. Data were analyzed using
      descriptive statistics, Pearson correlation coefficient, and linear regression
      analysis to determine the extent of the effect of social capital on burnout. The
      study showed an inverse association between social capital and burnout. The
      intensity of the relationship was -0.451 (P<0.0001). Also, the linear regression
      model of social capital on burnout variable showed that the regression
      coefficient of social capital equaled -0.34. The determination coefficient of
      this regression model indicated that social capital explained 20% of burnout
      changes. The results showed high burnout in emotional exhaustion dimension and an
      inverse association between social capital and burnout. Thus, attempts should be
      made to promote social capital dimensions among nurses. Given the inevitability
      of job stress in a nursing environment, and managers should plan on improving the
      working conditions and training techniques to deal with such stress. 

PMID- 25871019
TI  - Association between iron deficiency anemia and Helicobacter pylori infection
      among children under six years in Iran.
AB  - This study was conducted to evaluate the association between H. pylori infection
      and Iron deficiency anemia (IDA) among preschool children (age range: 40-75
      months) at a tertiary referral hospital in Tehran.In a case-control study, the
      prevalence of H. pylori seropositivity was compared between 64 children with IDA
      diagnosis and 70 healthy non-anemic sex- and age-matched controls. Totally, 52
      (81.3%) children with IDA and 10 (14.3%) non-anemic controls had a positive
      antibody level for H. pylori specific IgG and the difference between two groups
      was statistically significant (P<0.0001). H. pylori infection had a significant
      high prevalence among preschool patients with IDA. Eradication of H. pylori
      infection is recommended for patients with refractory IDA. 

PMID- 25871020
TI  - Lateral lower face and neck contouring following burn injury.
AB  - The neck is normally a concave and highly mobile structure. Facial and cervical
      skin is prone to burn scar contracture because of its thin nature. The goal of
      treatment is to reconstruct this region to achieve a good aesthetic outcome and
      also normal neck and chin mobilization. This study was conducted to compare the
      effect of one row of suture and three rows of suture in critical points of the
      neck to recreate cervicomandibular angle for better contouring of the neck. A
      cross-sectional study was performed from July 2006 until August 2010. A total of
      65 patients underwent lower lateral face and neck burn scar contracture
      reconstruction. The mean age of participants was 25.5 years old. After designing
      a local flap, in 31 patients we applied one row of suture. In 34 patients, we
      used three rows of suture on each side of the neck incorporation with  the
      recipient bed and the flap dermis or capsule to recreate a natural lower lateral
      face and neck contour (P<0.001). The standard deviation in hospitalization was 7
      +/- 2 days for group A and 6 +/- 1 days for group B. In a two years follow-up, no
      blunting of cervicomandibular angle occurred and three rows of suture were
      superior according to present findings. 

PMID- 25871021
TI  - Frequency and epidemiologic aspects of male infertility.
AB  - According to different geographical conditions, human health in different sub
      regions of the world and cultural differences, the male factor infertility has
      heterogeneous causes in the world. This study was performed in an attempt to
      clarify the associated factors which might play a role in this respect in a group
      of Iranian infertile men. This study was a cross - sectional, descriptive and
      retrospective study. The information was obtained from the men who had attended
      the clinic from March 2004-2006. The factors which were studied in this research
      are the demographic characteristics, smoking, addiction, alcohol drinking, and
      exposure to lead, cimetidine and history of surgery. In 23.7 % of couples the
      cause of infertility was pure male factor and in 19.3 % of them the problem was
      related to male and female factor both. The most important associated factors for
      male factor included smoking (29%) and history of varicocele operation (22%).
      Since the quality of individual and social life is related to fertility state, it
      seems that more comprehensive studies on factors affecting male fertility at the
      community level are justified and recommended. 

PMID- 25871022
TI  - Expression of the pituitary tumor transforming gene (PTTG1) in pheochromocytoma
      as a potential marker for distinguishing benign versus malignant tumors.
AB  - The Distinction between malignant and benign pheochromocytoma has always been a
      diagnostic challenge over the last decades. To date, the only reliable criterion
      is metastasis. The aim of the present study was to investigate the possible
      expression of pituitary-tumor transforming gene (PTTG1) and retinoblastoma (Rb)
      in benign and malignant pheochromocytoma. Paraffin blocks of 44 and 11 patients
      diagnosed with benign and malignant pheochromocytoma were collected. Parameters
      such as sex, age, tumor size, necrosis, and histological features were compared
      between the benign and malignant groups as well as immunohistochemical labeling
      using specific antibodies. PTTG1 showed negative expression in all (44) benign
      and 9 out of 11 (81.8%) malignant tumors with only 2 out of 11 (18.2%) malignant
      tumors showed positive reactivity for PTTG1 (P: 0.037) with spindle cell
      histological pattern in both of them (P: 0.013). Although Rb expression in
      malignant tumors (81.8%) was slightly more than the benign ones (52.3%), no
      statistically significant correlation was observed (P: 0.087). These results
      suggest that PTTG1 immunostaining may play a key role in distinguishing between
      benign and malignant phaeochromocytoma. However, larger studies are necessary to
      confirm the outcomes of the present study. 

PMID- 25871023
TI  - Principles of primary survey and resuscitation in cases of pediatric trauma.
AB  - Trauma is a common cause of death and disability in children. Proper approach to
      pediatric trauma involves adherence to ABCDE sequence in the primary survey and
      resuscitation in order to promptly recognize and manage life-threatening
      conditions immediately. This readily reviewed sequence includes A: establishment
      and maintenance of a patent airway while maintaining cervical spine
      immobilization; B: evaluation of breathing, ventilation and oxygenation,
      immediate treatment of tension pneumothorax, open pneumothorax and massive
      hemothorax; C: evaluation and treatment of circulatory compromise and shock; D:
      Disability and Neurologic Status, assessment of signs of increased intracranial
      pressure and impending cerebral herniation; and E: Exposure while preventing
      hypothermia. Implementing these assessment and management priorities can result
      in more favorable outcomes. 

PMID- 25871024
TI  - A giant subserosal uterine leiomyoma mimicking an abdominal mass: multimodal
      imaging data.
AB  - Giant uterine leiomyomas are extremely rare neoplasms and are challenging both
      diagnostically and therapeutically. A 49-year-old premenopausal female presented
      at our Department complaining of abdominal pain and distention for several years.
      Ultrasound (US), color Doppler US, abdominal computed tomography imaging after
      administration of contrast material, and abdominal magnetic resonance imaging
      were performed. Histopathologic examination revealed a pedunculated subserosal
      uterine leiomyoma. In this case report, we present abdominopelvic multimodal
      radiologic imaging findings of our patient with a giant subserosal uterine
      leiomyoma, in conjunction with histopathological findings. 

PMID- 25871025
TI  - Magnetic resonance imaging of Whipple's disease confined to the CNS presenting
      with multiple intracerebral mass lesions.
AB  - We report a patient diagnosed with Whipple's disease (WD) who presented only with
      neurological symptoms. Neuroimaging (MRI) showed lesions with marked mass effect
      similar to infiltrative tumors, which were hypersignal on long TR and hyposignal
      on short TR images, located in several areas of the brain. In serial controls,
      lesions resolved with gliosis and atrophic changes as well as migration of active
      infiltrative-like lesions to new areas. MR findings of the brain WD are
      discussed, which confirmed by stereotactic brain biopsy. Familiarity with the
      range of possible MR imaging appearances of WD enables the radiologist to place
      WD more effectively on the differential diagnosis which motivates the clinician
      to consider both the diagnosis and early initiation of treatment; so, this may
      significantly impact outcome. Moreover, repeated MR investigations may serve as a
      valuable method to evaluate efficacy of treatment and long term follow-up of WD
      involving the CNS. 

PMID- 25871026
TI  - Thrombotic tendency in patients with Behcet's disease.

PMID- 25871027
TI  - Manganese-catalyzed late-stage aliphatic C-H azidation.
AB  - We report a manganese-catalyzed aliphatic C-H azidation reaction that can
      efficiently convert secondary, tertiary, and benzylic C-H bonds to the
      corresponding azides. The method utilizes aqueous sodium azide solution as the
      azide source and can be performed under air. Besides its operational simplicity,
      the potential of this method for late-stage functionalization has been
      demonstrated by successful azidation of various bioactive molecules with yields
      up to 74%, including the important drugs pregabalin, memantine, and the
      antimalarial artemisinin. Azidation of celestolide with a chiral manganese salen
      catalyst afforded the azide product in 70% ee, representing a Mn-catalyzed
      enantioselective aliphatic C-H azidation reaction. Considering the versatile
      roles of organic azides in modern chemistry and the ubiquity of aliphatic C-H
      bonds in organic molecules, we envision that this Mn-azidation method will find
      wide application in organic synthesis, drug discovery, and chemical biology. 

PMID- 25871028
TI  - Condition for emergence of the Floquet-Gibbs state in periodically driven open
      systems.
AB  - We study probability distribution of a steady state of a periodically driven
      system coupled to a thermal bath by using a quantum master equation in the weak
      coupling limit. It is proved that, even when the external field is strong, the
      probability distribution is independent of the detailed nature of the thermal
      bath under the following conditions: (i) the Hamiltonian of the relevant system
      is bounded and the period of the driving field is short, (ii) the Hamiltonians
      for the driving field at different times commute, and (iii) the Hamiltonians of
      the driving field and of the interaction between the relevant system and the
      thermal bath commute. It is shown that the steady state is described by the Gibbs
      distribution of the Floquet states of the relevant system at the temperature of
      the thermal bath. 

PMID- 25871029
TI  - Anisotropic isometric fluctuation relations in experiment and theory on a self
      propelled rod.
AB  - The isometric fluctuation relation (IFR) [P. I. Hurtado et al., Proc. Natl. Acad.
      Sci. USA 108, 7704 (2011)10.1073/pnas.1013209108] relates the relative
      probability of current fluctuations of fixed magnitude in different spatial
      directions. We test its validity in an experiment on a tapered rod, rendered
      motile by vertical vibration and immersed in a sea of spherical beads. We analyze
      the statistics of the velocity vector of the rod and show that they depart
      significantly from the IFR of Hurtado et al. Aided by a Langevin-equation model
      we show that our measurements are largely described by an anisotropic
      generalization of the IFR [R. Villavicencio et al., Europhys. Lett. 105, 30009
      (2014)10.1209/0295-5075/105/30009], with no fitting parameters, but with a
      discrepancy in the prefactor whose origin may lie in the detailed statistics of
      the microscopic noise. The experimentally determined large-deviation function of
      the velocity vector has a kink on a curve in the plane. 

PMID- 25871030
TI  - Exact asymptotics of the current in boundary-driven dissipative quantum chains in
      large external fields.
AB  - A boundary-driven quantum master equation for a general inhomogeneous
      (nonintegrable) anisotropic Heisenberg spin-1/2 chain, or an equivalent nearest
      neighbor interacting spinless fermion chain, is considered in the presence of a
      strong external field f. We present an exact closed form expression for large f
      asymptotics of the current in the presence of a pure incoherent source and sink
      dissipation at the boundaries. In application, we demonstrate an arbitrary large
      current rectification in the presence of the interaction. 

PMID- 25871031
TI  - Frustrated packing of spheres in a flat container under symmetry-breaking bias.
AB  - We study statistical properties of packings of monodisperse spheres in a flat
      box. After "gravitational" filling and appropriate agitation, a nearly regular
      (in plane) but frustrated (normal to the plane) triangular lattice forms, where
      beads at individual sites touch either the front or back wall. It has striking
      analogies to order in antiferromagnetic Ising spin models. When tilting the
      container, Earth's gravitational field mimics external forces similar to magnetic
      fields in the spin systems. While packings in vertical containers adopt a
      frustrated state with statistical correlations between neighboring sites, the
      configurations continuously approach the predictions of a random Ising model when
      the cell tilt is increased. Our experiments offer insights into both the
      influence of geometrical constraints on random granular packing and a descriptive
      example of frustrated ordering. 

PMID- 25871032
TI  - Crystallization and reentrant melting of charged colloids in nonpolar solvents.
AB  - We explore the crystallization of charged colloidal particles in a nonpolar
      solvent mixture. We simultaneously charge the particles and add counterions to
      the solution with aerosol-OT (AOT) reverse micelles. At low AOT concentrations,
      the charged particles crystallize into body-centered-cubic (bcc) or face-centered
      cubic (fcc) Wigner crystals; at high AOT concentrations, the increased screening
      drives a thus far unobserved reentrant melting transition. We observe an
      unexpected scaling of the data with particle size, and account for all behavior
      with a model that quantitatively predicts both the reentrant melting and the data
      collapse. 

PMID- 25871033
TI  - Suppressing turbulence of self-propelling rods by strongly coupled passive
      particles.
AB  - The strong turbulence suppression, mainly for large-scale modes, of two
      dimensional self-propelling rods, by increasing the long-range coupling strength
      Gamma of low-concentration passive particles, is numerically demonstrated. It is
      found that large-scale collective rod motion in forms of swirls or jets is mainly
      contributed from well-aligned dense patches, which can push small poorly aligned
      rod patches and uncoupled passive particles. The more efficient momentum transfer
      and dissipation through increasing passive particle coupling leads to the
      formation of a more ordered and slowed down network of passive particles, which
      competes with coherent dense active rod clusters. The frustration of active rod
      alignment ordering and coherent motion by the passive particle network, which
      interrupt the inverse cascading of forming large-scale swirls, is the key for
      suppressing collective rod motion with scales beyond the interpassive distance,
      even in the liquid phase of passive particles. The loosely packed active rods are
      weakly affected by increasing passive particle coupling due to the weak rod
      particle interaction. They mainly contribute to the small-scale modes and high
      speed motion. 

PMID- 25871034
TI  - Liquid-gas asymmetry and the wave-vector-dependent surface tension.
AB  - Attempts to extend the capillary-wave theory of fluid interfacial fluctuations to
      microscopic wavelengths, by introducing an effective wave-vector (q)-dependent
      surface tension sigmaeff(q), have encountered difficulties. There is no consensus
      as to even the shape of sigmaeff(q). By analyzing a simple density functional
      model of the liquid-gas interface, we identify different schemes for separating
      microscopic observables into background and interfacial contributions. In order
      for the backgrounds of the density-density correlation function and local
      structure factor to have a consistent and physically meaningful interpretation in
      terms of weighted bulk gas and liquid contributions, the background of the total
      structure factor must be characterized by a microscopic q-dependent length
      zeta(q) not identified previously. The necessity of including the q dependence of
      zeta(q) is illustrated explicitly in our model and has wider implications; i.e.,
      in typical experimental and simulation studies, an indeterminacy in zeta(q) will
      always be present, reminiscent of the cutoff used in capillary-wave theory. This
      leads inevitably to a large uncertainty in the q dependence of sigmaeff(q).

PMID- 25871035
TI  - Topological defect transformation and structural transition of two-dimensional
      colloidal crystals across the nematic to smectic-A phase transition.
AB  - We observe that topological defects in nematic colloids are strongly influenced
      by the elasticity and onset of smectic layering across the nematic (N) to smectic
      A (SmA) phase transition. When approaching the SmA phase from above, the nematic
      hyperbolic hedgehog defect that accompanies a spherical colloidal inclusion is
      transformed into a focal conic line in the SmA phase. This phase transformation
      has a strong influence on the pairwise colloidal interaction and is responsible
      for a structural transition of two-dimensional colloidal crystals. The
      pretransitional behavior of the point defect is supported by Landau-de Gennes Q
      tensor modeling accounting for the increasing elastic anisotropy. 

PMID- 25871036
TI  - Leaning-type polar smectic-C phase in a freely suspended bent-core liquid crystal
      film.
AB  - A rich variety of responsive behavior occurs in complex structured fluids due to
      their lower symmetries. On the other hand, fluid disorder tends to increase the
      symmetry of liquid crystal mesophases. Here, we report direct evidence for the
      existence of a mesophase with CS symmetry. The observations are based on optical
      studies of director inversion walls in freely suspended films in electric fields
      under obliquely incident light. This phase is distinguished by the polarization
      lying in the molecular tilt plane in freely suspended films. Such a low-symmetry
      polar fluid phase has been long predicted to occur in bent-core liquid crystals.
      The stability of this phase is attributed to the bent shape of the mesogens and
      dominating dispersion interactions.

PMID- 25871037
TI  - Reconstructing weighted networks from dynamics.
AB  - We present a method that reconstructs both the links and their relative coupling
      strength of bidirectional weighted networks. Our method requires only
      measurements of node dynamics as input. Using several examples, we demonstrate
      that our method can give accurate results for weighted random and weighted scale
      free networks with both linear and nonlinear dynamics. 

PMID- 25871038
TI  - Interaction of scroll waves in an excitable medium: Reconnection and repulsion.
AB  - Scroll waves of reentrant activity and their interactions pose a serious threat
      to cardiac health. In experiments with the Belousov-Zhabotinsky reaction we
      demonstrate the interaction of scroll waves. We show that depending on their
      mutual orientation, two scroll rings can push each other away and rupture on
      touching the system boundary, or they can reconnect to form a single, large ring.
      Reconnection only occurs when the filaments lie within one core length of each
      other. The reconnected filament has extended lifetimes, which could have serious
      implications in systems where they occur. The experimental results are explained
      on the basis of a simple numerical model. 

PMID- 25871039
TI  - Detecting and interpreting distortions in hierarchical organization of complex
      time series.
AB  - Hierarchical organization is a cornerstone of complexity and multifractality
      constitutes its central quantifying concept. For model uniform cascades the
      corresponding singularity spectra are symmetric while those extracted from
      empirical data are often asymmetric. Using selected time series representing such
      diverse phenomena as price changes and intertransaction times in financial
      markets, sentence length variability in narrative texts, Missouri River
      discharge, and sunspot number variability as examples, we show that the resulting
      singularity spectra appear strongly asymmetric, more often left sided but in some
      cases also right sided. We present a unified view on the origin of such effects
      and indicate that they may be crucially informative for identifying the
      composition of the time series. One particularly intriguing case of this latter
      kind of asymmetry is detected in the daily reported sunspot number variability.
      This signals that either the commonly used famous Wolf formula distorts the real
      dynamics in expressing the largest sunspot numbers or, if not, that their
      dynamics is governed by a somewhat different mechanism. 

PMID- 25871040
TI  - Coriolis effects enhance lift on revolving wings.
AB  - At high angles of attack, an aircraft wing stalls. This dreaded event is
      characterized by the development of a leading edge vortex on the upper surface of
      the wing, followed by its shedding which causes a drastic drop in the aerodynamic
      lift. At similar angles of attack, the leading edge vortex on an insect wing or
      an autorotating seed membrane remains robustly attached, ensuring high sustained
      lift. What are the mechanisms responsible for both leading edge vortex attachment
      and high lift generation on revolving wings? We review the three main hypotheses
      that attempt to explain this specificity and, using direct numerical simulations
      of the Navier-Stokes equations, we show that the latter originates in Coriolis
      effects. 

PMID- 25871041
TI  - Hydrodynamic synchronization of autonomously oscillating optically trapped
      particles.
AB  - Ellipsoidal micron-sized colloidal particles can oscillate spontaneously when
      trapped in a focused laser beam. If two oscillating particles are held in
      proximity their oscillations synchronize through hydrodynamic interactions. The
      degree of synchronization depends on the distance between the oscillators and on
      their orientation. Due to the anisotropic nature of hydrodynamic coupling the
      synchronization is strongest when particles are arranged along the direction of
      oscillations. Similar behavior is observed for many oscillating particles
      arranged in a row. Experimental observations are well reproduced with a model
      that uses a phenomenological description of the optical force and hydrodynamic
      interactions. Our results show that oscillating ellipsoidal particles can serve
      as a model system for studying hydrodynamic synchronization between biological
      cilia. 

PMID- 25871042
TI  - Pinning and gas oversaturation imply stable single surface nanobubbles.
AB  - Surface nanobubbles are experimentally known to survive for days at hydrophobic
      surfaces immersed in gas-oversaturated water. This is different from bulk
      nanobubbles, which are pressed out by the Laplace pressure against any gas
      oversaturation and dissolve in submilliseconds, as derived by Epstein and Plesset
      [J. Chem. Phys. 18, 1505 (1950)]. Pinning of the contact line has been speculated
      to be the reason for the stability of the surface nanobubbles. Building on an
      exact result by Popov [Phys. Rev. E 71, 036313 (2005)] on coffee stain
      evaporation, here we confirm this speculation by an exact calculation for single
      surface nanobubbles. It is based only on (i) the diffusion equation, (ii) Laplace
      pressure, and (iii) Henry's equation, i.e., fluid dynamical equations which are
      all known to be valid down to the nanometer scale. The crucial parameter is the
      gas oversaturation zeta of the liquid. At the stable equilibrium, the gas
      overpressures due to this oversaturation and the Laplace pressure balance. The
      theory predicts how the contact angle of the pinned bubble depends on zeta and
      the surface nanobubble's footprint lateral extension L. It also predicts an upper
      lateral extension threshold for stable surface nanobubbles to exist.

PMID- 25871043
TI  - Differential ablator-fuel adiabat tuning in indirect-drive implosions.
AB  - We propose a design adjustment to the high foot laser pulse [T. R. Dittrich et
      al., Phys. Rev. Lett. 112, 055002 (2014)] that is predicted to lower the fuel
      adiabat, increase compression and neutron production, but maintain similar
      ablation front growth. This is accomplished by lowering the laser power between
      the first and the second pulses (the "trough") so that the first shock remains
      strong initially but decays as it transits the ablator and enters the capsule
      fuel in a process similar to direct-drive "adiabat shaping" [S. E. Bodner et al.,
      Phys. Plasmas 7, 2298 (2000)]. Integrated hohlraum simulations show that hohlraum
      cooling is sufficient to launch decaying shocks with adequate symmetry control,
      suggesting that adiabat shaping may be possible with indirect-drive implosions.
      Initial experiments show the efficacy of this technique.

PMID- 25871044
TI  - Laboratory study of avalanches in magnetized plasmas.
AB  - It is demonstrated that a novel heating configuration applied to a large and cold
      magnetized plasma allows the study of avalanche phenomena under controlled
      conditions. Intermittent collapses of the plasma pressure profile, associated
      with unstable drift-Alfven waves, exhibit a two-slope power-law spectrum with
      exponents near -1 at lower frequencies and in the range of -2 to -4 at higher
      frequencies. A detailed mapping of the spatiotemporal evolution of a single
      avalanche event is presented. 

PMID- 25871045
TI  - Beyond the gain exponent: Effect of damping, scale length, and speckle length on
      stimulated scatter.
AB  - Three-dimensional wave propagation simulations and experiments show that the gain
      exponent, an often used metric to assess the likelihood of stimulated Brillouin
      scatter, is insufficient and must be augmented with another parameter, Nr, the
      ratio of the resonance length, Lres, to the laser speckle length. The damping
      rate of ion acoustic waves, nu, and thus Lres, which is proportional to nu, are
      easily varied with plasma species composition, e.g., by varying the ratio of
      hydrogen and carbon ions. As Nr decreases, stimulated Brillouin scattering
      increases despite the same gain exponent.

PMID- 25871046
TI  - Direct observation of the two-plasmon-decay common plasma wave using ultraviolet
      Thomson scattering.
AB  - A 263-nm Thomson-scattering beam was used to directly probe two-plasmon-decay
      (TPD) excited electron plasma waves (EPWs) driven by between two and five 351-nm
      beams on the OMEGA Laser System. The amplitude of these waves was nearly
      independent of the number of drive beams at constant overlapped intensity,
      showing that the observed EPWs are common to the multiple beams. In an
      experimental configuration where the Thomson-scattering diagnostic was not wave
      matched to the common TPD EPWs, a broad spectrum of TPD-driven EPWs was observed,
      indicative of nonlinear effects associated with TPD saturation. Electron plasma
      waves corresponding to Langmuir decay of TPD EPWs were observed in both Thomson
      scattering spectra, suggesting the Langmuir decay instability as a TPD saturation
      mechanism. Simulated Thomson-scattering spectra from three-dimensional numerical
      solutions of the extended Zakharov equations of TPD are in excellent agreement
      with the experimental spectra and verify the presence of the Langmuir decay
      instability. 

PMID- 25871047
TI  - High-order path-integral Monte Carlo methods for solving quantum dot problems.
AB  - The conventional second-order path-integral Monte Carlo method is plagued with
      the sign problem in solving many-fermion systems. This is due to the large number
      of antisymmetric free-fermion propagators that are needed to extract the ground
      state wave function at large imaginary time. In this work we show that optimized
      fourth-order path-integral Monte Carlo methods, which use no more than five free
      fermion propagators, can yield accurate quantum dot energies for up to 20
      polarized electrons with the use of the Hamiltonian energy estimator. 

PMID- 25871048
TI  - Finite-temperature crossovers in periodic disordered systems.
AB  - We consider the static properties of periodic structures in weak random disorder.
      We apply a functional renormalization group approach (FRG) and a Gaussian
      variational method (GVM) to study their displacement correlations. We focus in
      particular on the effects of temperature and we compute explicitly the crossover
      length scales separating different regimes in the displacement correlation
      function. We compare the FRG and GVM results and find excellent agreement. We
      show that the FRG predicts, in addition, the existence of a third length scale
      associated with the screening of the disorder by thermal fluctuations and discuss
      a protocol to observe it. 

PMID- 25871049
TI  - Universality classes for thermal transport in one-dimensional oscillator systems.
AB  - Two universality classes for thermal transport in one-dimensional oscillator
      systems are proposed. In class A the asymptotic behavior of the frequency
      dependent thermal conductivity is kappa(omega)~omega-1/2, whereas the bulk
      viscosity is finite. In class B the asymptotic behavior of the thermal
      conductivity is kappa~omega-alpha, where alpha<0.4, and the frequency dependent
      bulk viscosity has the same asymptotic behavior as the thermal conductivity. It
      is further proposed that the criterion for membership in class A is that the
      ratio of specific heat capacities gamma=cP/cV=1. A one-dimensional cubic-plus
      quartic coupled oscillator is examined at conditions for which gamma=1 but P?0.
      It is found that the system belongs to class A, in agreement with the proposed
      criterion. Additionally, it is proposed that examination of whether a system has
      a well-defined bulk Prandtl number is a more reliable way of determining whether
      a system is in class A or class B.

PMID- 25871050
TI  - Fiber bundle model with highly disordered breaking thresholds.
AB  - We present a study of the fiber bundle model using equal load-sharing dynamics
      where the breaking thresholds of the fibers are drawn randomly from a power-law
      distribution of the form p(b)~b-1 in the range 10-beta to 10beta. Tuning the
      value of beta continuously over a wide range, the critical behavior of the fiber
      bundle has been studied both analytically as well as numerically. Our results
      are: (i) The critical load sigmac(beta,N) for the bundle of size N approaches its
      asymptotic value sigmac(beta) as sigmac(beta,N)=sigmac(beta)+AN-1/nu(beta), where
      sigmac(beta) has been obtained analytically as sigmac(beta)=10beta/(2betaeln10)
      for beta>=betau=1/(2ln10), and for beta<betau the weakest fiber failure leads to
      the catastrophic breakdown of the entire fiber bundle, similar to brittle
      materials, leading to sigma_{c}(beta)=10-beta; (ii) the fraction of broken fibers
      right before the complete breakdown of the bundle has the form 1-1/(2betaln10);
      (iii) the distribution D(Delta) of the avalanches of size Delta follows a power
      law D(Delta)~Delta-xi with xi=5/2 for Delta?Deltac(beta) and xi=3/2 for
      Delta?Deltac(beta), where the crossover avalanche size Deltac(beta)=2/(1-e10
      2beta)2.

PMID- 25871051
TI  - Path integral control and state-dependent feedback.
AB  - In this paper we address the problem of computing state-dependent feedback
      controls for path integral control problems. To this end we generalize the path
      integral control formula and utilize this to construct parametrized state
      dependent feedback controllers. In addition, we show a relation between control
      and importance sampling: Better control, in terms of control cost, yields more
      efficient importance sampling, in terms of effective sample size. The optimal
      control provides a zero-variance estimate. 

PMID- 25871052
TI  - Critical Casimir force in the presence of random local adsorption preference.
AB  - We study the critical Casimir force for a film geometry in the Ising universality
      class. We employ a homogeneous adsorption preference on one of the confining
      surfaces, while the opposing surface exhibits quenched random disorder, leading
      to a random local adsorption preference. Disorder is characterized by a parameter
      p, which measures, on average, the portion of the surface that prefers one
      component, so that p=0,1 correspond to homogeneous adsorption preference. By
      means of Monte Carlo simulations of an improved Hamiltonian and finite-size
      scaling analysis, we determine the critical Casimir force. We show that by tuning
      the disorder parameter p, the system exhibits a crossover between an attractive
      and a repulsive force. At p=1/2, disorder allows to effectively realize Dirichlet
      boundary conditions, which are generically not accessible in classical fluids.
      Our results are relevant for the experimental realizations of the critical
      Casimir force in binary liquid mixtures. 

PMID- 25871053
TI  - Survival probability of a Brownian motion in a planar wedge of arbitrary angle.
AB  - We study the survival probability and the first-passage time distribution for a
      Brownian motion in a planar wedge with infinite absorbing edges. We generalize
      existing results obtained for wedge angles of the form pi/n with n a positive
      integer to arbitrary angles, which in particular cover the case of obtuse angles.
      We give explicit and simple expressions of the survival probability and the first
      passage time distribution in which the difference between an arbitrary angle and
      a submultiple of pi is contained in three additional terms. As an application, we
      obtain the short-time development of the survival probability in a wedge of
      arbitrary angle. 

PMID- 25871054
TI  - Maximum-entropy description of animal movement.
AB  - We introduce a class of maximum-entropy states that naturally includes within it
      all of the major continuous-time stochastic processes that have been applied to
      animal movement, including Brownian motion, Ornstein-Uhlenbeck motion, integrated
      Ornstein-Uhlenbeck motion, a recently discovered hybrid of the previous models,
      and a new model that describes central-place foraging. We are also able to
      predict a further hierarchy of new models that will emerge as data quality
      improves to better resolve the underlying continuity of animal movement. Finally,
      we also show that Langevin equations must obey a fluctuation-dissipation theorem
      to generate processes that fall from this class of maximum-entropy distributions
      when the constraints are purely kinematic. 

PMID- 25871055
TI  - Fractional diffusion on a fractal grid comb.
AB  - A grid comb model is a generalization of the well known comb model, and it
      consists of N backbones. For N=1 the system reduces to the comb model where
      subdiffusion takes place with the transport exponent 1/2. We present an exact
      analytical evaluation of the transport exponent of anomalous diffusion for finite
      and infinite number of backbones. We show that for an arbitrarily large but
      finite number of backbones the transport exponent does not change. Contrary to
      that, for an infinite number of backbones, the transport exponent depends on the
      fractal dimension of the backbone structure. 

PMID- 25871056
TI  - Edwards's statistical mechanics of crumpling networks in crushed self-avoiding
      sheets with finite bending rigidity.
AB  - This paper is devoted to the crumpling of thin matter. The Edwards-like
      statistical mechanics of crumpling networks in a crushed self-avoiding sheet with
      finite bending rigidity is developed. The statistical distribution of crease
      lengths is derived. The relationship between sheet packing density and
      hydrostatic pressure is established. The entropic contribution to the crumpling
      network rigidity is outlined. The effects of plastic deformations and sheet self
      contacts on crumpling mechanics are discussed. Theoretical predictions are in
      good agreement with available experimental data and results of numerical
      simulations. Thus, the findings of this work provide further insight into the
      physics of crumpling and mechanical properties of crumpled soft matter. 

PMID- 25871057
TI  - Congestion phenomena caused by matching pennies in evolutionary games.
AB  - Evolutionary social dilemma games are extended by an additional matching-pennies
      game that modifies the collected payoffs. In a spatial version players are
      distributed on a square lattice and interact with their neighbors. First, we show
      that the matching-pennies game can be considered as the microscopic force of the
      Red Queen effect that breaks the detailed balance and induces eddies in the
      microscopic probability currents if the strategy update is analogous to the
      Glauber dynamics for the kinetic Ising models. The resulting loops in probability
      current breaks symmetry between the chessboardlike arrangements of strategies via
      a bottleneck effect occurring along the four-edge loops in the microscopic
      states. The impact of this congestion is analogous to the application of a
      staggered magnetic field in the Ising model; that is, the order-disorder critical
      transition is wiped out by noise. It is illustrated that the congestion induced
      symmetry breaking can be beneficial for the whole community within a certain
      region of parameters. 

PMID- 25871058
TI  - Narrow escape problem with a mixed trap and the effect of orientation.
AB  - We consider the mean first passage time (MFPT) of a two-dimensional diffusing
      particle to a small trap with a distribution of absorbing and reflecting
      sections. High-order asymptotic formulas for the MFPT and the fundamental
      eigenvalue of the Laplacian are derived which extend previously obtained results
      and show how the orientation of the trap affects the mean time to capture. We
      obtain a simple geometric condition which gives the optimal trap alignment in
      terms of the gradient of the regular part of a regular part of a Green's function
      and a certain alignment vector. We find that subdividing the absorbing portions
      of the trap reduces the mean first passage time of the diffusing particle. In the
      scenario where the trap undergoes prescribed motion in the domain, the MFPT is
      seen to be particularly sensitive to the orientation of the trap. 

PMID- 25871059
TI  - Localization in one-dimensional chains with Levy-type disorder.
AB  - We study Anderson localization of the classical lattice waves in a chain with
      mass impurities distributed randomly through a power-law relation s-(1+alpha)
      with s as the distance between two successive impurities and alpha>0. This model
      of disorder is long-range correlated and is inspired by the peculiar structure of
      the complex optical systems known as Levy glasses. Using theoretical arguments
      and numerics, we show that in the regime in which the average distance between
      impurities is finite with infinite variance, the small-frequency behavior of the
      localization length is xi{omega)~omega-alpha. The physical interpretation of this
      result is that, for small frequencies and long wavelengths, the waves feel an
      effective disorder whose fluctuations are scale dependent. Numerical simulations
      show that an initially localized wave-packet attains, at large times, a
      characteristic inverse power-law front with an alpha-dependent exponent which can
      be estimated analytically.

PMID- 25871060
TI  - Integrodifferential formulations of the continuous-time random walk for solute
      transport subject to bimolecular A+B->0 reactions: From micro- to mesoscopic.
AB  - We develop continuous-time random walk (CTRW) equations governing the transport
      of two species that annihilate when in proximity to one another. In comparison
      with catalytic or spontaneous transformation reactions that have been previously
      considered in concert with CTRW, both species have spatially variant
      concentrations that require consideration. We develop two distinct formulations.
      The first treats transport and reaction microscopically, potentially capturing
      behavior at sharp fronts, but at the cost of being strongly nonlinear. The
      second, mesoscopic, formulation relies on a separation-of-scales technique we
      develop to separate microscopic-scale reaction and upscaled transport. This
      simplifies the governing equations and allows treatment of more general reaction
      dynamics, but requires stronger smoothness assumptions of the solution. The
      mesoscopic formulation is easily tractable using an existing solution from the
      literature (we also provide an alternative derivation), and the generalized
      master equation (GME) for particles undergoing A+B->0 reactions is presented. We
      show that this GME simplifies, under appropriate circumstances, to both the GME
      for the unreactive CTRW and to the advection-dispersion-reaction equation. An
      additional major contribution of this work is on the numerical side: to
      corroborate our development, we develop an indirect particle-tracking-partial
      integro-differential-equation (PIDE) hybrid verification technique which could be
      applicable widely in reactive anomalous transport. Numerical simulations support
      the mesoscopic analysis. 

PMID- 25871061
TI  - Stochasticity enhances the gaining of bet-hedging strategies in contact-process
      like dynamics.
AB  - In biology and ecology, individuals or communities of individuals living in
      unpredictable environments often alternate between different evolutionary
      strategies to spread and reduce risks. Such behavior is commonly referred to as
      "bet-hedging." Long-term survival probabilities and population sizes can be much
      enhanced by exploiting such hybrid strategies. Here, we study the simplest
      possible birth-death stochastic model in which individuals can choose among a
      poor but safe strategy, a better but risky alternative, or a combination of both.
      We show analytically and computationally that the benefits derived from bet
      hedging strategies are much stronger for higher environmental variabilities
      (large external noise) and/or for small spatial dimensions (large intrinsic
      noise). These circumstances are typically encountered by living systems, thus
      providing us with a possible justification for the ubiquitousness of bet-hedging
      in nature. 

PMID- 25871062
TI  - Behavior of the dielectric constant of Ar near the critical point.
AB  - The fundamental question of the behavior of the dielectric constant near the
      critical point is addressed using Ar as the probe system. The neighborhood of the
      liquid-vapor critical point of Ar is accessed by classical Monte Carlo simulation
      and then explicit quantum mechanics calculations are performed to study the
      behavior of the dielectric constant. The theoretical critical temperature is
      determined by calculating the position of the discontinuity of the specific heat
      and is found to be at T(c)Theor=148.7K, only 2 K below the experimental value.
      The large fluctuations and the inhomogeneity of the density that characterize the
      critical point rapidly disappear and are not seen at T=T(c)Theor+2K. The
      structure of Ar obtained by the radial distribution function is found to be in
      very good agreement with experiment both in the liquid phase and 2 K above the
      critical temperature. The behavior of the dielectric constant is then analyzed
      after calculating the static dipole polarizability and using a many-body Clausius
      Mossotti equation. The dielectric constant shows a density-independent behavior
      around the critical density, 2 K above the critical temperature. At this point,
      the calculated value of the dielectric constant is 1.173+/-0.005 in excellent
      agreement with the experimental value of 1.179.

PMID- 25871063
TI  - Scaling laws and bulk-boundary decoupling in heat flow.
AB  - When driven out of equilibrium by a temperature gradient, fluids respond by
      developing a nontrivial, inhomogeneous structure according to the governing
      macroscopic laws. Here we show that such structure obeys strikingly simple
      scaling laws arbitrarily far from equilibrium, provided that both macroscopic
      local equilibrium and Fourier's law hold. Extensive simulations of hard disk
      fluids confirm the scaling laws even under strong temperature gradients, implying
      that Fourier's law remains valid in this highly nonlinear regime, with putative
      corrections absorbed into a nonlinear conductivity functional. In addition, our
      results show that the scaling laws are robust in the presence of strong finite
      size effects, hinting at a subtle bulk-boundary decoupling mechanism which
      enforces the macroscopic laws on the bulk of the finite-sized fluid. This allows
      one to measure the marginal anomaly of the heat conductivity predicted for hard
      disks. 

PMID- 25871064
TI  - Towards a thermodynamics of active matter.
AB  - Self-propulsion allows living systems to display self-organization and unusual
      phase behavior. Unlike passive systems in thermal equilibrium, active matter
      systems are not constrained by conventional thermodynamic laws. A question
      arises, however, as to what extent, if any, can concepts from classical
      thermodynamics be applied to nonequilibrium systems like active matter. Here we
      use the new swim pressure perspective to develop a simple theory for predicting
      phase separation in active matter. Using purely mechanical arguments we generate
      a phase diagram with a spinodal and critical point, and define a nonequilibrium
      chemical potential to interpret the "binodal." We provide a generalization of
      thermodynamic concepts like the free energy and temperature for nonequilibrium
      active systems. Our theory agrees with existing simulation data both
      qualitatively and quantitatively and may provide a framework for understanding
      and predicting the behavior of nonequilibrium active systems. 

PMID- 25871065
TI  - Thermodynamics of creating correlations: Limitations and optimal protocols.
AB  - We establish a rigorous connection between fundamental resource theories at the
      quantum scale. Correlations and entanglement constitute indispensable resources
      for numerous quantum information tasks. However, their establishment comes at the
      cost of energy, the resource of thermodynamics, and is limited by the initial
      entropy. Here, the optimal conversion of energy into correlations is
      investigated. Assuming the presence of a thermal bath, we establish general
      bounds for arbitrary systems and construct a protocol saturating them. The amount
      of correlations, quantified by the mutual information, can increase at most
      linearly with the available energy, and we determine where the linear regime
      breaks down. We further consider the generation of genuine quantum correlations,
      focusing on the fundamental constituents of our universe: fermions and bosons.
      For fermionic modes, we find the optimal entangling protocol. For bosonic modes,
      we show that while Gaussian operations can be outperformed in creating
      entanglement, their performance is optimal for high energies. 

PMID- 25871066
TI  - Quantum thermodynamics of general quantum processes.
AB  - Accurately describing work extraction from a quantum system is a central
      objective for the extension of thermodynamics to individual quantum systems. The
      concepts of work and heat are surprisingly subtle when generalizations are made
      to arbitrary quantum states. We formulate an operational thermodynamics suitable
      for application to an open quantum system undergoing quantum evolution under a
      general quantum process by which we mean a completely positive and trace
      preserving map. We derive an operational first law of thermodynamics for such
      processes and show consistency with the second law. We show that heat, from the
      first law, is positive when the input state of the map majorizes the output
      state. Moreover, the change in entropy is also positive for the same majorization
      condition. This makes a strong connection between the two operational laws of
      thermodynamics. 

PMID- 25871067
TI  - Pathwise thermodynamic structure in population dynamics.
AB  - We reveal thermodynamic structure in population dynamics with phenotype
      switching. Mean fitness for a population of organisms is determined by a
      thermodynamic variational principle described by the large deviation of phenotype
      switching dynamics. Owing to this variational principle, a response relation of
      the mean fitness with respect to changes of environments and phenotype-switching
      dynamics is represented as a thermodynamic differential form. Furthermore, we
      discuss the strength of the selection by using the difference between time
      forward and time-backward (retrospective) processes. 

PMID- 25871068
TI  - Crossover aspects in Ising strips under the influence of variable surface fields
      and a grain boundary.
AB  - I use an exact variational formulation of Mikheev and Fisher to study the
      critical Ising strip with a grain boundary and confining surfaces characterized
      by arbitrary and different surface magnetic fields. Energy density profiles that
      serve as order parameters of the system within the used method show strong
      nonmonotonous behavior in the vicinity of confining surfaces. I consider short
      distance expansion of energy density profiles. New universal amplitudes
      associated with distant-wall corrections exhibit nontrivial crossover behaviors
      from positive to negative values as the field's variables are continuously
      varied. Casimir amplitudes calculated in a self-contained manner are
      characterized by complex manifolds which may comprise two disconnected positive
      wings separated by an area of negative values. I define and determine the
      generalized de Gennes-Fisher amplitude, which strongly suggests that a stress
      tensor is present within one of the distant-wall corrections. This is an
      unanticipated result given that a similar discovery for standard extraordinary
      (E) and ordinary (O) surface universality classes was based on the conformal
      invariance symmetry, which is broken under the present boundary conditions. A
      grain boundary essentially influences both energy density profiles and Casimir
      amplitudes, besides surface fields with a number of accompanying features that
      are examined in detail. We present closed analytic forms of energy density
      profiles for standard (N) and (O) BCs: ENN(x,g),EOO(x,g),ENO(x,g) [(N) is the
      normal surface universality class, g is the grain boundary's strength, x is the
      relative distance x:=z/L with L as a film width], thus enabling us to deduce
      their important symmetry properties and to have a detailed insight into their
      general behaviors.

PMID- 25871069
TI  - Universality in the spectral and eigenfunction properties of random networks.
AB  - By the use of extensive numerical simulations, we show that the nearest-neighbor
      energy-level spacing distribution P(s) and the entropic eigenfunction
      localization length of the adjacency matrices of Erdos-Renyi (ER) fully random
      networks are universal for fixed average degree xi=alphaN (alpha and N being the
      average network connectivity and the network size, respectively). We also
      demonstrate that the Brody distribution characterizes well P(s) in the transition
      from alpha=0, when the vertices in the network are isolated, to alpha=1, when the
      network is fully connected. Moreover, we explore the validity of our findings
      when relaxing the randomness of our network model and show that, in contrast to
      standard ER networks, ER networks with diagonal disorder also show universality.
      Finally, we also discuss the spectral and eigenfunction properties of small-world
      networks. 

PMID- 25871070
TI  - Completely packed O(n) loop models and their relation with exactly solved
      coloring models.
AB  - We investigate the completely packed O(n) loop model on the square lattice, and
      its generalization to an Eulerian graph model, which follows by including cubic
      vertices which connect the four incoming loop segments. This model includes
      crossing bonds as well. Our study was inspired by existing exact solutions of the
      so-called coloring model due to Schultz and Perk [Phys. Rev. Lett. 46, 629
      (1981)], which is shown to be equivalent with our generalized loop model. We
      explore the physical properties and the phase diagram of this model by means of
      transfer-matrix calculations and finite-size scaling. The exact results, which
      include seven one-dimensional branches in the parameter space of our generalized
      loop model, are compared to our numerical results. The results for the phase
      behavior also extend to parts of the parameter space beyond the exactly solved
      subspaces. One of the exactly solved branches describes the case of
      nonintersecting loops and was already known to correspond with the ordering
      transition of the Potts model. Another exactly solved branch, describing a model
      with nonintersecting loops and cubic vertices, corresponds with a first-order,
      Ising-like phase transition for n>2. For 1<n<2, this branch is interpreted in
      terms of a low-temperature O(n) phase with corner-cubic anisotropy. For n>2 this
      branch is the locus of a first-order phase boundary between a phase with a hard
      square, lattice-gas-like ordering and a phase dominated by cubic vertices. A mean
      field argument explains the first-order nature of this transition.

PMID- 25871071
TI  - Rigidity percolation by next-nearest-neighbor bonds on generic and regular
      isostatic lattices.
AB  - We study rigidity percolation transitions in two-dimensional central-force
      isostatic lattices, including the square and the kagome lattices, as next-nearest
      neighbor bonds ("braces") are randomly added to the system. In particular, we
      focus on the differences between regular lattices, which are perfectly periodic,
      and generic lattices with the same topology of bonds but whose sites are at
      random positions in space. We find that the regular square and kagome lattices
      exhibit a rigidity percolation transition when the number of braces is ~LlnL,
      where L is the linear size of the lattice. This transition exhibits features of
      both first-order and second-order transitions: The whole lattice becomes rigid at
      the transition, and a diverging length scale also exists. In contrast, we find
      that the rigidity percolation transition in the generic lattices occur when the
      number of braces is very close to the number obtained from Maxwell's law for
      floppy modes, which is ~L. The transition in generic lattices is a very sharp
      first-order-like transition, at which the addition of one brace connects all
      small rigid regions in the bulk of the lattice, leaving only floppy modes on the
      edge. We characterize these transitions using numerical simulations and develop
      analytic theories capturing each transition. Our results relate to other
      interesting problems, including jamming and bootstrap percolation. 

PMID- 25871072
TI  - Simulation of stationary Gaussian noise with regard to the Langevin equation with
      memory effect.
AB  - We present an efficient method for simulating a stationary Gaussian noise with an
      arbitrary covariance function, and then we study numerically the impact of time
      correlated noise on the time evolution of a (1+1)-dimensional generalized
      Langevin equation by comparing also to analytical results. Finally, we apply our
      method to the generalized Langevin equation with an external harmonic and double
      well potential. 

PMID- 25871073
TI  - Parallel multicanonical study of the three-dimensional Blume-Capel model.
AB  - We study the thermodynamic properties of the three-dimensional Blume-Capel model
      on the simple cubic lattice by means of computer simulations. In particular, we
      implement a parallelized variant of the multicanonical approach and perform
      simulations by keeping a constant temperature and crossing the phase boundary
      along the crystal-field axis. We obtain numerical data for several temperatures
      in both the first- and second-order regime of the model. Finite-size scaling
      analyses provide us with transition points and the dimensional scaling behavior
      in the numerically demanding first-order regime, as well as a clear verification
      of the expected Ising universality in the respective second-order regime.
      Finally, we discuss the scaling behavior in the vicinity of the tricritical
      point. 

PMID- 25871074
TI  - Heat conduction in a chain of dissociating particles: Effect of dimensionality.
AB  - The paper considers heat conduction in a model chain of composite particles with
      hard core and elastic external shell. Such model mimics three main features of
      realistic interatomic potentials--hard repulsive core, quasilinear behavior in a
      ground state, and possibility of dissociation. It has become clear recently that
      this latter feature has crucial effect on convergence of the heat conduction
      coefficient in thermodynamic limit. We demonstrate that in one-dimensional chain
      of elastic particles with hard core the heat conduction coefficient also
      converges, as one could expect. Then we explore effect of dimensionality on the
      heat transport in this model. For this sake, longitudinal and transversal motions
      of the particles are allowed in a long narrow channel. With varying width of the
      channel, we observe sharp transition from "one-dimensional" to "two-dimensional"
      behavior. Namely, the heat conduction coefficient drops by about order of
      magnitude for relatively small widening of the channel. This transition is not
      unique for the considered system. Similar phenomenon of transition to quasi-1D
      behavior with growth of aspect ratio of the channel is observed also in a gas of
      densely packed hard (billiard) particles, both for two- and three-dimensional
      cases. It is the case despite the fact that the character of transition in these
      two systems is not similar, due to different convergence properties of the heat
      conductivity. In the billiard model, the divergence pattern of the heat
      conduction coefficient smoothly changes from logarithmic to power-like law with
      increase of the length.

PMID- 25871075
TI  - Kinetic model for the finite-time thermodynamics of small heat engines.
AB  - We study a molecular engine constituted by a gas of N~102 molecules enclosed
      between a massive piston and a thermostat. The force acting on the piston and the
      temperature of the thermostat are cyclically changed with a finite period tau. In
      the adiabatic limit tau->infinity, even for finite size N, the average work and
      heat reproduce the thermodynamic values, recovering the Carnot result for the
      efficiency. The system exhibits a stall time tau* where the net work is zero: for
      tau<tau* it consumes work instead of producing it, acting as a refrigerator or as
      a heat sink. At tau>tau* the efficiency at maximum power is close to the Curzorn
      Ahlborn limit. The fluctuations of work and heat display approximatively a
      Gaussian behavior. Based upon kinetic theory, we develop a three-variables
      Langevin model in which the piston's position and velocity are linearly coupled
      together with the internal energy of the gas. The model reproduces many of the
      system's features, such as the inversion of the work's sign, the efficiency at
      maximum power, and the approximate shape of the fluctuations. A further
      simplification in the model allows us to compute analytically the average work,
      explaining its nontrivial dependence on tau.

PMID- 25871076
TI  - Low-temperature Glauber dynamics under weak competing interactions.
AB  - We consider the low but nonzero-temperature regimes of the Glauber dynamics in a
      chain of Ising spins with first- and second-neighbor interactions J1,J2. For 0<
      J2/|J1|<1 it is known that at T=0 the dynamics is both metastable and
      noncoarsening, while being always ergodic and coarsening in the limit of T->0+.
      Based on finite-size scaling analyses of relaxation times, here we argue that in
      that latter situation the asymptotic kinetics of small or weakly frustrated 
      J2/|J1| ratios is characterized by an almost ballistic dynamic exponent z?1.03(2)
      and arbitrarily slow velocities of growth. By contrast, for noncompeting
      interactions the coarsening length scales are estimated to be almost diffusive.

PMID- 25871077
TI  - Fixation properties of subdivided populations with balancing selection.
AB  - In subdivided populations, migration acts together with selection and genetic
      drift and determines their evolution. Building upon a recently proposed method,
      which hinges on the emergence of a time scale separation between local and global
      dynamics, we study the fixation properties of subdivided populations in the
      presence of balancing selection. The approximation implied by the method is
      accurate when the effective selection strength is small and the number of
      subpopulations is large. In particular, it predicts a phase transition between
      species coexistence and biodiversity loss in the infinite-size limit and, in
      finite populations, a nonmonotonic dependence of the mean fixation time on the
      migration rate. In order to investigate the fixation properties of the subdivided
      population for stronger selection, we introduce an effective coarser description
      of the dynamics in terms of a voter model with intermediate states, which
      highlights the basic mechanisms driving the evolutionary process. 

PMID- 25871078
TI  - Dynamic criticality far from equilibrium: One-loop flow of Burgers-Kardar-Parisi
      Zhang systems with broken Galilean invariance.
AB  - Burgers-Kardar-Parisi-Zhang (KPZ) scaling has recently (re-) surfaced in a
      variety of physical contexts, ranging from anharmonic chains to quantum systems
      such as open superfluids, in which a variety of random forces may be encountered
      and/or engineered. Motivated by these developments, we here provide a
      generalization of the KPZ universality class to situations with long-ranged
      temporal correlations in the noise, which purposefully break the Galilean
      invariance that is central to the conventional KPZ solution. We compute the phase
      diagram and critical exponents of the KPZ equation with 1/f noise (KPZ1/f) in
      spatial dimensions 1<=d<4 using the dynamic renormalization group with a
      frequency cutoff technique in a one-loop truncation. Distinct features of KPZ1/f
      are (i) a generically scale-invariant, rough phase at high noise levels that
      violates fluctuation-dissipation relations and exhibits hyperthermal statistics
      even in d=1, (ii) a fine-tuned roughening transition at which the flow fulfills
      an emergent thermal-like fluctuation-dissipation relation, that separates the
      rough phase from (iii) a massive phase in 1<d<4 (in d=1 the interface is always
      rough). We point out potential connections to nonlinear hydrodynamics with a
      reduced set of conservation laws and noisy quantum liquids.

PMID- 25871079
TI  - Open quantum reaction-diffusion dynamics: Absorbing states and relaxation.
AB  - We consider an extension of classical stochastic reaction-diffusion (RD) dynamics
      to open quantum systems. We study a class of models of hard-core particles on a
      one-dimensional lattice whose dynamics is generated by a quantum master operator.
      Particle hopping is coherent while reactions, such as pair annihilation or pair
      coalescence, are dissipative. These are quantum open generalizations of the A+A
      >? and A+A->A classical RD models. We characterize the relaxation of the state
      towards the stationary regime via a decomposition of the system Hilbert space
      into transient and recurrent subspaces. We provide a complete classification of
      the structure of the recurrent subspace (and the nonequilibrium steady states) in
      terms of the dark states associated to the quantum master operator and its
      general spectral properties. We also show that, in one dimension, relaxation
      towards these absorbing dark states is slower than that predicted by a mean-field
      analysis due to fluctuation effects, in analogy with what occurs in classical RD
      systems. Numerical simulations of small systems suggest that the decay of the
      density in one dimension, in both the open quantum A+A->? and A+A->A systems,
      behaves asymptotically as t-b with 1/2<b<1.

PMID- 25871080
TI  - Bottom-up model of adsorption and transport in multiscale porous media.
AB  - We develop a model of transport in multiscale porous media which accounts for
      adsorption in the different porosity scales. This model employs statistical
      mechanics to upscale molecular simulation and describe adsorption and transport
      at larger time and length scales. Using atom-scale simulations, which capture the
      changes in adsorption and transport with temperature, pressure, pore size, etc.,
      this approach does not assume any adsorption or flow type. Moreover, by relating
      the local chemical potential MU(r) and density rho(r), the present model accounts
      for adsorption effects and possible changes in the confined fluid state upon
      transport. This model constitutes a bottom-up framework of adsorption and
      transport in multiscale materials as it (1) describes the adsorption-transport
      interplay, (2) accounts for the hydrodynamics breakdown at the nm scale, and (3)
      is multiscale. 

PMID- 25871081
TI  - Failure criterion for materials with spatially correlated mechanical properties.
AB  - The role of spatially correlated mechanical elements in the failure behavior of
      heterogeneous materials represented by fiber bundle models (FBMs) was evaluated
      systematically for different load redistribution rules. Increasing the range of
      spatial correlation for FBMs with local load sharing is marked by a transition
      from ductilelike failure characteristics into brittlelike failure. The study
      identified a global failure criterion based on macroscopic properties (external
      load and cumulative damage) that is independent of spatial correlation or load
      redistribution rules. This general metric could be applied to assess the
      mechanical stability of complex and heterogeneous systems and thus provide an
      important component for early warning of a class of geophysical ruptures. 

PMID- 25871082
TI  - Traveling wave in a three-dimensional array of conformist and contrarian
      oscillators.
AB  - We consider a system of conformist and contrarian oscillators coupled locally in
      a three-dimensional cubic lattice and explore collective behavior of the system.
      The conformist oscillators attractively interact with the neighbor oscillators
      and therefore tend to be aligned with the neighbors' phase. The contrarian
      oscillators interact repulsively with the neighbors and therefore tend to be out
      of phase with them. In this paper, we investigate whether many peculiar dynamics
      that have been observed in the mean-field system with global coupling can emerge
      even with local coupling. In particular, we pay attention to the possibility that
      a traveling wave may arise. We find that the traveling wave occurs due to
      coupling asymmetry and not by global coupling; this observation confirms that the
      global coupling is not essential to the occurrence of a traveling wave in the
      system. The traveling wave can be a mechanism for the coherent rhythm generation
      of the circadian clock or of hormone secretion in biological systems under local
      coupling. 

PMID- 25871083
TI  - Entropy-production-driven oscillators in simple nonequilibrium networks.
AB  - The development of tractable nonequilibrium simulation methods represents a
      bottleneck for efforts to describe the functional dynamics that occur within
      living cells. We here employ a nonequilibrium approach called the lambda ensemble
      to characterize the dissipative dynamics of a simple Markovian network driven by
      an external potential. In the highly dissipative regime brought about by the
      lambda bias, we observe a dynamical structure characteristic of cellular
      architectures: The entropy production drives a damped oscillator over state
      populations in the network. We illustrate the properties of such oscillations in
      weakly and strongly driven regimes, and we discuss how control structures
      associated with the "dynamical phase transition" in the system can be related to
      switches and oscillators in cellular dynamics. 

PMID- 25871084
TI  - Work done and irreversible entropy production in a suddenly quenched quantum spin
      chain with asymmetrical excitation spectra.
AB  - In this paper, we extend the studies on the emergent thermodynamics in a quenched
      quantum Ising chain (QIC) [R. Dorner, J. Goold, C. Cormick, M. Paternostro, and
      V. Vedral, Phys. Rev. Lett. 109, 160601 (2012)] to a more general quantum spin
      chain with asymmetrical excitation spectra. We verify that the Jarzynski and
      Tasaki-Crooks relations are still tenable in this system. As an example, we
      discuss the behaviors of the work done and irreversible entropy production
      induced by a sudden quenching in the anisotropic XY chain in a transverse field
      with the XZY-YZX type of three-site interactions. Different from the QIC, this
      system has the phase transitions not only between two gapped phases, but also
      between gapped (or gapless) and gapless phases at zero temperature. We discuss
      the effects of quantum phase transitions on the work done and irreversible
      entropy production at low temperature.

PMID- 25871085
TI  - Fixed-point distributions of short-range Ising spin glasses on hierarchical
      lattices.
AB  - Fixed-point distributions for the couplings of Ising spin glasses with nearest
      neighbor interactions on hierarchical lattices are investigated numerically.
      Hierarchical lattices within the Migdal-Kadanoff family with fractal dimensions
      in the range 2.58<=D<=7, as well as a lattice of the Wheatstone-Bridge family
      with fractal dimension D~3.58 are considered. Three initial distributions for the
      couplings are analyzed, namely, the Gaussian, bimodal, and uniform ones. In all
      cases, after a few iterations of the renormalization-group procedure, the
      associated probability distributions approached universal fixed shapes. For
      hierarchical lattices of the Migdal-Kadanoff family, the fixed-point
      distributions were well fitted either by stretched exponentials, or by q-Gaussian
      distributions; both fittings recover the expected Gaussian limit as D->infinity.
      In the case of the Wheatstone-Bridge lattice, the best fit was found by means of
      a stretched-exponential distribution. 

PMID- 25871086
TI  - Stochastic dynamics of collective modes for Brownian dipoles.
AB  - The individual motion of a colloidal particle is described by an overdamped
      Langevin equation. When rotational degrees of freedom are relevant, these are
      described by a corresponding Langevin process. Our purpose is to show that the
      microscopic local density of colloids, in terms of a space and rotation state,
      also evolves according to a Langevin equation. The latter can then be used as the
      starting point of a variety of approaches, ranging from dynamical density
      functional theory to mode-coupling approximations. 

PMID- 25871087
TI  - Solution of the explosive percolation quest. II. Infinite-order transition
      produced by the initial distributions of clusters.
AB  - We describe the effect of power-law initial distributions of clusters on ordinary
      percolation and its generalizations, specifically, models of explosive
      percolation processes based on local optimization. These aggregation processes
      were shown to exhibit continuous phase transitions if the evolution starts from a
      set of disconnected nodes. Since the critical exponents of the order parameter in
      explosive percolation transitions turned out to be very small, these transitions
      were first believed to be discontinuous. In this article we analyze the evolution
      starting from clusters of nodes whose sizes are distributed according to a power
      law. We show that these initial distributions change dramatically the position
      and order of the phase transitions in these problems. We find a particular
      initial power-law distribution producing a peculiar effect on explosive
      percolation, namely, before the emergence of the percolation cluster, the system
      is in a "critical phase" with an infinite generalized susceptibility. This
      critical phase is absent in ordinary percolation models with any power-law
      initial conditions. The transition from the critical phase is an infinite-order
      phase transition, which resembles the scenario of the Berezinskii-Kosterlitz
      Thouless phase transition. We obtain the critical singularity of susceptibility
      at this peculiar infinite-order transition in explosive percolation. It turns out
      that susceptibility in this situation does not obey the Curie-Weiss law. 

PMID- 25871088
TI  - Thermodynamic geometry of supercooled water.
AB  - The thermodynamic curvature scalar R is evaluated for supercooled water with a
      two-state equation of state correlated with the most recent available
      experimental data. This model assumes a liquid-liquid critical point. Our
      investigation extends the understanding of the thermodynamic behavior of R
      considerably. We show that R diverges to -infinity when approaching the assumed
      liquid-liquid critical point. This limit is consistent with all of the fluid
      critical point models known so far. In addition, we demonstrate a sign change of
      R along the liquid-liquid line from negative near the critical point to positive
      on moving away from the critical point in the low density "ice-like" liquid
      phase. We also trace out the Widom line in phase space. In addition, we
      investigate increasing correlation length in supercooled water and compare our
      results with recent published small angle x-ray scattering measurements. 

PMID- 25871089
TI  - Slicing the three-dimensional Ising model: Critical equilibrium and coarsening
      dynamics.
AB  - We study the evolution of spin clusters on two-dimensional slices of the three
      dimensional Ising model in contact with a heat bath after a sudden quench to a
      subcritical temperature. We analyze the evolution of some simple initial
      configurations, such as a sphere and a torus, of one phase embedded into the
      other, to confirm that their area disappears linearly with time and to establish
      the temperature dependence of the prefactor in each case. Two generic kinds of
      initial states are later used: equilibrium configurations either at infinite
      temperature or at the paramagnetic-ferromagnetic phase transition. We investigate
      the morphological domain structure of the coarsening configurations on two
      dimensional slices of the three-dimensional system, compared with the behavior of
      the bidimensional model. 

PMID- 25871090
TI  - Driven diffusive systems with mutually interactive Langmuir kinetics.
AB  - We investigate the simple one-dimensional driven model, the totally asymmetric
      exclusion process, coupled to mutually interactive Langmuir kinetics. This model
      is motivated by recent studies on clustering of motor proteins on microtubules.
      In the proposed model, the attachment and detachment rates of a particle are
      modified depending upon the occupancy of neighboring sites. We first obtain
      continuum mean-field equations and in certain limiting cases obtain analytic
      solutions. We show how mutual interactions increase (decrease) the effects of
      boundaries on the phase behavior of the model. We perform Monte Carlo simulations
      and demonstrate that our analytical approximations are in good agreement with the
      numerics over a wide range of model parameters. We present phase diagrams over a
      selective range of parameters. 

PMID- 25871091
TI  - Double Lynden-Bell structure of low-energy quasistationary distributions in the
      Hamiltonian mean-field model.
AB  - In the Hamiltonian mean-field model, we study the core-halo structure of low
      energy quasistationary states under unsteady water-bag type initial conditions.
      The core-halo structure results in the superposition of two independent Lynden
      Bell distributions. We examine the completeness of the Lynden-Bell relaxation and
      the relaxation between these two Lynden-Bell distributions. 

PMID- 25871092
TI  - Phase transitions in a frustrated Ising antiferromagnet on a square lattice.
AB  - The phase transitions occurring in the frustrated Ising square antiferromagnet
      with first- (J1<0) and second-nearest-neighbor (J2<0) interactions are studied
      within the framework of the effective-field theory with correlations based on the
      different cluster sizes and for a wide range of R=J2/|J1|. Despite the simplicity
      of the model, it has proved difficult to precisely determine the order of the
      phase transitions. In contrast to the previous effective-field study, we have
      found a first-order transition line in the region close to R=-0.5 not only
      between the superantiferromagnetic and paramagnetic (R<-0.5) but also between
      antiferromagnetic and paramagnetic (R>-0.5) phases.

PMID- 25871093
TI  - Bicritical universality of the anisotropic Heisenberg model in a crystal field.
AB  - The bicritical properties of the three-dimensional classical anisotropic
      Heisenberg model in a crystal field are investigated through extensive Monte
      Carlo simulations on a simple cubic lattice, using Metropolis and Wolff
      algorithms. Field-mixing and multidimensional histogram techniques were employed
      in order to compute the probability distribution function of the extensive
      conjugate variables of interest and, using finite-size scaling analysis, the
      first-order transition line of the model was precisely located. The fourth-order
      cumulant of the order parameter was then calculated along this line and the
      bicritical point located with good precision from the cumulant crossings. The
      bicritical properties of this point were further investigated through the
      measurement of the universal probability distribution function of the order
      parameter. The results lead us to conclude that the studied bicritical point
      belongs in fact to the three-dimensional Heisenberg universality class. 

PMID- 25871094
TI  - Preservation of thermodynamic structure in model reduction.
AB  - Based on the availability of an invariant manifold, we develop a model-reduction
      procedure that preserves thermodynamic structure. More concretely, we construct
      the Poisson and irreversible brackets of the general equation for the
      nonequilibrium reversible-irreversible coupling of nonequilibrium thermodynamics
      by means of the ideas originally introduced for handling constraints. The general
      ideas are then applied to the Kramers problem, that is, the description of
      transitions between two potential wells separated by a high barrier. This example
      reveals how a fortuitous cancellation mechanism that allows a logarithmic entropy
      to generate a linear diffusion equation is inherited by a master equation
      resulting from model reduction. 

PMID- 25871095
TI  - Glassy slowdown and replica-symmetry-breaking instantons.
AB  - Glass-forming liquids exhibit a dramatic dynamical slowdown as the temperature is
      lowered. This can be attributed to relaxation proceeding via large structural
      rearrangements whose characteristic size increases as the system cools. These
      cooperative rearrangements are well modeled by instantons in a replica effective
      field theory, with the size of the dominant instanton encoding the liquid's
      cavity point-to-set correlation length. Varying the parameters of the effective
      theory corresponds to varying the statistics of the underlying free-energy
      landscape. We demonstrate that, for a wide range of parameters, replica-symmetry
      breaking instantons dominate. The detailed structure of the dominant instanton
      provides a rich window into point-to-set correlations and glassy dynamics. 

PMID- 25871096
TI  - Monte Carlo study of magnetization dynamics in uniaxial ferromagnetic nanowires
      in the presence of oscillating and biased magnetic fields.
AB  - We examine the dynamic phase transition properties of ferromagnetic uniaxial
      nanowires with tunable radius r in the presence of both oscillating and biased
      magnetic fields. Variation of the transition temperature as a function of
      amplitude h0 of the oscillating field has been analyzed in the absence of
      magnetic bias hb and at constant oscillation period P. We find that the
      transition temperature as a function of h0 exhibits an exponential decay
      behavior. We also investigate the magnetization dynamics in terms of magnetic
      hysteresis loops as functions of the parameters hb, h0, and P. Our calculations
      are qualitatively in agreement with the recent experimental results obtained for
      uniaxial cobalt films in which it was concluded that the bias field hb is the
      conjugate field of the dynamic order parameter.

PMID- 25871097
TI  - Multiple-contact discrete-element model for simulating dense granular media.
AB  - This article presents a new force model for performing quantitative simulations
      of dense granular materials. Interactions between multiple contacts (MC) on the
      same grain are explicitly taken into account. Our readily applicable MC-DEM
      method retains all the advantages of discrete-element method simulations and does
      not require the use of costly finite-element methods. The new model closely
      reproduces our recent experimental measurements, including contact force
      distributions in full 3D, at all compression levels of the packing up to the
      experimental maximum limit of 13%. Comparisons with classic simulations using the
      nondeformable spheres approach, as well as with alternative models for
      interactions between multiple contacts, are provided. The success of our model,
      compared to these alternatives, demonstrates that interactions between multiple
      contacts on each grain must be included for dense granular packings. 

PMID- 25871098
TI  - Average balance equations, scale dependence, and energy cascade for granular
      materials.
AB  - A new averaging method linking discrete to continuum variables of granular
      materials is developed and used to derive average balance equations. Its novelty
      lies in the choice of the decomposition between mean values and fluctuations of
      properties which takes into account the effect of gradients. Thanks to a local
      homogeneity hypothesis, whose validity is discussed, simplified balance equations
      are obtained. This original approach solves the problem of dependence of some
      variables on the size of the averaging domain obtained in previous approaches
      which can lead to huge relative errors (several hundred percentages). It also
      clearly separates affine and nonaffine fields in the balance equations. The
      resulting energy cascade picture is discussed, with a particular focus on
      unidirectional steady and fully developed flows for which it appears that the
      contact terms are dissipated locally unlike the kinetic terms which contribute to
      a nonlocal balance. Application of the method is demonstrated in the
      determination of the macroscopic properties such as volume fraction, velocity,
      stress, and energy of a simple shear flow, where the discrete results are
      generated by means of discrete particle simulation. 

PMID- 25871099
TI  - Effects of shape and size polydispersity on strength properties of granular
      materials.
AB  - By means of extensive contact dynamics simulations, we analyze the combined
      effects of polydispersity both in particle size and in particle shape, defined as
      the degree of shape irregularity, on the shear strength and microstructure of
      sheared granular materials composed of pentagonal particles. We find that the
      shear strength is independent of the size span, but unexpectedly, it declines
      with increasing shape polydispersity. At the same time, the solid fraction is an
      increasing function of both the size span and the shape polydispersity. Hence,
      the densest and loosest packings have the same shear strength. At the scale of
      the particles and their contacts, we analyze the connectivity of particles, force
      transmission, and friction mobilization as well as their anisotropies. We show
      that stronger forces are carried by larger particles and propped by an increasing
      number of small particles. The independence of shear strength with regard to size
      span is shown to be a consequence of contact network self-organization, with the
      falloff of contact anisotropy compensated by increasing force anisotropy. 

PMID- 25871100
TI  - Horizontal flow and surface patterns in a vertically vibrated annular granular
      layer.
AB  - A set of experiments was carried out on the motion of granular materials in a
      vertically vibrated annular system with a sawtooth-shaped base. We observed the
      coexistence of granular flow and surface patterns such as periodic subharmonic
      waves and kink pairs. Different patterns can transit each other as control
      parameters vary. The flow varies with space and time, and oppositely directed
      flows can occur at different levels and different moments. The magnitude and
      direction of the flow depend on the parameters defining the system in a complex
      manner. The motion of the patterns relates to the granular flow in a different
      way from that in which the wave in an ordinary fluid relates to the moving fluid.
      A preliminary explanation is given to our experimental findings. 

PMID- 25871101
TI  - Competition between geometrically induced and density-driven segregation
      mechanisms in vibrofluidized granular systems.
AB  - The behaviors of granular systems are sensitive to a wide variety of particle
      properties, including size, density, elasticity, and shape. Differences in any of
      these properties between particles in a granular mixture may lead to segregation,
      or "demixing," a process of great industrial relevance. Despite the known
      influence of particle geometry in granular systems, a considerable fraction of
      research into these systems concerns only uniformly spherical particles. We
      address, for the case of vertically vibrated granular systems, the important
      question of whether the introduction of differing particle geometries entirely
      invalidates our existing knowledge based on purely spherical granulates, or
      whether current models may simply be adapted to account for the effects of
      particle shape. We demonstrate that while shape effects can indeed influence the
      dynamical and segregative behaviors of a granular system, the segregative
      mechanisms associated with particle geometry are decidedly secondary to those
      related to particle density. The relevant control parameters determining the
      extent of geometrically induced segregation are established. Finally, a manner in
      which shape effects may be accounted for in simulations utilizing purely
      spherical particles is proposed. 

PMID- 25871102
TI  - Role of defects in the onset of wall-induced granular convection.
AB  - We investigate the onset of wall-induced convection in vertically vibrated
      granular matter by means of experiments and two-dimensional computer simulations.
      In both simulations and experiments we find that the wall-induced convection
      occurs inside the bouncing bed region of the parameter space, in which the
      granular bed behaves like a bouncing ball. A good agreement between experiments
      and simulations is found for the peak vibration acceleration at which convection
      starts. By comparing the results of simulations initialized with and without
      defects, we find that the onset of convection occurs at lower vibration strengths
      in the presence of defects. Furthermore, we find that the convection of granular
      particles initialized in a perfect hexagonal lattice is related to the nucleation
      of defects and the process is described by an Arrhenius law. 

PMID- 25871103
TI  - Relevance of system size to the steady-state properties of tapped granular
      systems.
AB  - We investigate the steady-state packing fraction phi and force moment tensor
      Sigma of quasi-two-dimensional granular columns subjected to tapping. Systems of
      different height h and width L are considered. We find that phi and Sigma, which
      describe the macroscopic state of the system, are insensitive to L for L>50d
      (with d the grain diameter). However, results for granular columns of different
      heights cannot be conciliated. This suggests that comparison between results of
      different laboratories on this type of experiments can be done only for systems
      of same height. We show that a parameter E=1+(Aomega)2/(2gh), with A and omega
      the amplitude and frequency of the tap and g the acceleration of gravity, can be
      defined to characterize the tap intensity. This parameter is based on the
      effective flight of the granular bed, which takes into account the h dependency.
      When phi is plotted as a function of E, the data collapses for systems of
      different h. However, this parameter alone is unable to determine the steady
      state to be reached since different Sigma can be observed for a given E if
      different column heights are considered.

PMID- 25871104
TI  - Anisotropic stress correlations in two-dimensional liquids.
AB  - In this paper we demonstrate the presence of anisotropic stress correlations in
      the simulated two-dimensional liquids. Whereas the temporal correlation of
      macroscopic shear stress is known to contribute to viscosity via the Green-Kubo
      formula, the general question regarding angular dependence of the spatial
      correlation among atomic-level stresses in liquids without external shear has not
      been explored. We observed the apparent anisotropicity with well-defined symmetry
      which can be explained in terms of the elastic continuum theory by Eshelby. In
      addition, we found that the shear stress correlation is screened compared to the
      prediction by the elastic continuum theory, and the screening length depends on
      temperature and follows the power law, suggesting divergence around the glass
      transition temperature. The success of the Eshelby theory to explain the
      anisotropy of the stress correlations justifies the idea that the mismatch
      between the atom and its nearest neighbor cage produces the atomic-level stress
      as well as the long-range stress fields. 

PMID- 25871105
TI  - Structure of marginally jammed polydisperse packings of frictionless spheres.
AB  - We model the packing structure of a marginally jammed bulk ensemble of
      polydisperse spheres. To this end we expand on the granocentric model [Clusel et
      al., Nature (London) 460, 611 (2009)], explicitly taking into account rattlers.
      This leads to a relationship between the characteristic parameters of the
      packing, such as the mean number of neighbors and the fraction of rattlers, and
      the radial distribution function g(r). We find excellent agreement between the
      model predictions for g(r) and packing simulations, as well as experiments on
      jammed emulsion droplets. The observed quantitative agreement opens the path
      towards a full structural characterization of jammed particle systems for imaging
      and scattering experiments.

PMID- 25871106
TI  - Effects of temperature on spinodal decomposition and domain growth of liquid
      vapor systems with smoothed particle hydrodynamics.
AB  - We present a numerical method for simulations of spinodal decomposition of liquid
      vapor systems. The results are in excellent agreement with theoretical
      predictions for all expected time regimes from the initial growth of "homophase
      fluctuations" up to the inertial hydrodynamics regime. The numerical approach
      follows a modern formulation of the smoothed particle hydrodynamics method with a
      van der Waals equation of state and thermal conduction. The dynamics and thermal
      evolution of instantaneously temperature-quenched systems are investigated.
      Therefore, we introduce a simple scaling thermostat that allows thermal
      fluctuations at a constant predicted mean temperature. We find that the initial
      stage spinodal decomposition is strongly affected by the temperature field. The
      separated phases react on density changes with a change in temperature. Although,
      the thermal conduction acts very slowly, thermal deviations are eventually
      compensated. The domain growth in the late stage of demixing is found to be
      rather unaffected by thermal fluctuations. We observe a transition from the
      Lifshitz-Slyozov growth rate with 1/3 exponent to the inertial hydrodynamics
      regime with a rate of 2/3, only excepted from simulations near the critical point
      where the liquid droplets are observed to nucleate directly in a spherical shape.
      The transition between the growth regimes is found to occur earlier for higher
      initial temperatures. We explain this time dependency with the phase interfaces
      that become more diffuse and overlap with approaching the critical point. A
      prolonging behavior of the demixing process is observed and also expected to
      depend on temperature. It is further found that the observations can excellently
      explain the growth behavior for pure nonisothermal simulations that are performed
      without thermostat. 

PMID- 25871107
TI  - Entropy and kinetics of point defects in two-dimensional dipolar crystals.
AB  - We study in experiment and with computer simulation the free energy and the
      kinetics of vacancy and interstitial defects in two-dimensional dipolar crystals.
      The defects appear in different local topologies, which we characterize by their
      point group symmetry; Cn is the n-fold cyclic group and Dn is the dihedral group,
      including reflections. The frequency of different local topologies is not
      determined by their almost degenerate energies but is dominated by entropy for
      symmetric configurations. The kinetics of the defects is fully reproduced by a
      master equation in a multistate Markov model. In this model, the system is
      described by the state of the defect and the time evolution is given by
      transitions occurring with particular rates. These transition rate constants are
      extracted from experiments and simulations using an optimization procedure. The
      good agreement between experiment, simulation, and master equation thus provides
      evidence for the accuracy of the model.

PMID- 25871108
TI  - Coulomb energy of uniformly charged spheroidal shell systems.
AB  - We provide exact expressions for the electrostatic energy of uniformly charged
      prolate and oblate spheroidal shells. We find that uniformly charged prolate
      spheroids of eccentricity greater than 0.9 have lower Coulomb energy than a
      sphere of the same area. For the volume-constrained case, we find that a sphere
      has the highest Coulomb energy among all spheroidal shells. Further, we derive
      the change in the Coulomb energy of a uniformly charged shell due to small, area
      conserving perturbations on the spherical shape. Our perturbation calculations
      show that buckling-type deformations on a sphere can lower the Coulomb energy.
      Finally, we consider the possibility of counterion condensation on the spheroidal
      shell surface. We employ a Manning-Oosawa two-state model approximation to
      evaluate the renormalized charge and analyze the behavior of the equilibrium free
      energy as a function of the shell's aspect ratio for both area-constrained and
      volume-constrained cases. Counterion condensation is seen to favor the formation
      of spheroidal structures over a sphere of equal area for high values of shell
      volume fractions. 

PMID- 25871109
TI  - Brownian motion of single glycerol molecules in an aqueous solution as studied by
      dynamic light scattering.
AB  - Aqueous solutions of glycerol are investigated by dynamic light scattering (DLS)
      over the whole concentration range (10-98 wt.% water) and in the temperature
      range 283-303 K. The measurements reveal one slow relaxation process in the
      geometry of polarized light scattering. This process is present in the whole
      concentration range, although it is very weak at the highest and lowest water
      concentrations and is considerably slower than the structural alpha relaxation,
      which is too fast to be observed on the experimental time scale in the measured
      temperature range. The relaxation time of the observed process exhibits a 1/q2
      dependence, proving that it is due to long-range translational diffusion. The
      Stokes-Einstein relation is used to estimate the hydrodynamic radius of the
      diffusing particles and from these calculations it is evident that the observed
      relaxation process is due to the Brownian motion of single or a few glycerol
      molecules. The fact that it is possible to study the self-diffusion of such small
      molecules may stimulate a broadening of the research field used to be covered by
      the DLS technique.

PMID- 25871110
TI  - Shear-stress function approach of hydration layer based on the Green-Kubo
      formula.
AB  - We present the analytic expression of the stress correlation (SC) function for
      the ubiquitous hydration water layer (HWL) using the Green-Kubo equation and the
      shear modulus of HWL. The SC function is then experimentally obtained by
      measuring the viscoelastic properties of HWL using shear-mode dynamic force
      spectroscopy. Interestingly, the SC changes sign from positive to negative as the
      HWL thickness increases, where the shear stresses acting on the HWLs bound to two
      nearby surfaces are out of phase. We also suggest that the repulsive hydration
      force originates from the SC of HWL. Our results provide the first demonstration
      of the microscopic understanding of the HWL viscoelasticity and may allow a
      deeper insight on the HWL dynamics as well as the complex liquids. 

PMID- 25871111
TI  - Different mechanisms for dynamical arrest in largely asymmetric binary mixtures.
AB  - Using confocal microscopy we investigate binary colloidal mixtures with large
      size asymmetry, in particular the formation of dynamically arrested states of the
      large spheres. The volume fraction of the system is kept constant, and as the
      concentration of small spheres is increased we observe a series of transitions of
      the large spheres to different arrested states: an attractive glass, a gel, and
      an asymmetric glass. These states are distinguished by the degree of dynamical
      arrest and the amount of structural and dynamical heterogeneity. The transitions
      between two different arrested states occur through melting and the formation of
      a fluid state. While a space-spanning network of bonded particles is found in
      both arrested and fluid states, only arrested states are characterized by the
      presence of a space-spanning network of dynamically arrested particles. 

PMID- 25871112
TI  - Asymmetric crystallization during cooling and heating in model glass-forming
      systems.
AB  - We perform molecular dynamics (MD) simulations of the crystallization process in
      binary Lennard-Jones systems during heating and cooling to investigate atomic
      scale crystallization kinetics in glass-forming materials. For the cooling
      protocol, we prepared equilibrated liquids above the liquidus temperature Tl and
      cooled each sample to zero temperature at rate Rc. For the heating protocol, we
      first cooled equilibrated liquids to zero temperature at rate Rp and then heated
      the samples to temperature T>Tl at rate Rh. We measured the critical heating and
      cooling rates Rh* and Rc*, below which the systems begin to form a substantial
      fraction of crystalline clusters during the heating and cooling protocols. We
      show that Rh*>Rc* and that the asymmetry ratio Rh*/Rc* includes an intrinsic
      contribution that increases with the glass-forming ability (GFA) of the system
      and a preparation-rate dependent contribution that increases strongly as Rp->Rc*
      from above. We also show that the predictions from classical nucleation theory
      (CNT) can qualitatively describe the dependence of the asymmetry ratio on the GFA
      and preparation rate Rp from the MD simulations and results for the asymmetry
      ratio measured in Zr- and Au-based bulk metallic glasses (BMG). This work
      emphasizes the need for and benefits of an improved understanding of
      crystallization processes in BMGs and other glass-forming systems.

PMID- 25871113
TI  - Anisotropic elasticity of experimental colloidal Wigner crystals.
AB  - Colloidal particles interacting via a long-range repulsion can, in contrast to
      hard-sphere systems, exhibit crystalline ordering at low volume fraction. Here we
      experimentally investigate the structure and properties of such "colloidal Wigner
      crystals." We find a body-centered-cubic crystalline phase at volume fractions of
      phi?15%, which exhibits large fluctuations of individual particles from their
      average positions. We determine the three independent crystalline elastic
      constants and find that these crystals are very compliant and highly anisotropic.

PMID- 25871114
TI  - Model for the interpretation of nuclear magnetic resonance relaxometry of
      hydrated porous silicate materials.
AB  - Nuclear magnetic resonance (NMR) relaxation experimentation is an effective
      technique for probing the dynamics of proton spins in porous media, but
      interpretation requires the application of appropriate spin-diffusion models.
      Molecular dynamics (MD) simulations of porous silicate-based systems containing a
      quasi-two-dimensional water-filled pore are presented. The MD simulations suggest
      that the residency time of the water on the pore surface is in the range 0.03-12
      ns, typically 2-5 orders of magnitude less than values determined from fits to
      experimental NMR measurements using the established surface-layer (SL) diffusion
      models of Korb and co-workers [Phys. Rev. E 56, 1934 (1997)]. Instead, MD
      identifies four distinct water layers in a tobermorite-based pore containing
      surface Ca2+ ions. Three highly structured water layers exist within 1 nm of the
      surface and the central region of the pore contains a homogeneous region of
      bulklike water. These regions are referred to as layer 1 and 2 (L1, L2),
      transition layer (TL), and bulk (B), respectively. Guided by the MD simulations,
      a two-layer (2L) spin-diffusion NMR relaxation model is proposed comprising two
      two-dimensional layers of slow- and fast-moving water associated with L2 and
      layers TL+B, respectively. The 2L model provides an improved fit to NMR
      relaxation times obtained from cementitious material compared to the SL model,
      yields diffusion correlation times in the range 18-75 ns and 28-40 ps in good
      agreement with MD, and resolves the surface residency time discrepancy. The 2L
      model, coupled with NMR relaxation experimentation, provides a simple yet
      powerful method of characterizing the dynamical properties of proton-bearing
      porous silicate-based systems such as porous glasses, cementitious materials, and
      oil-bearing rocks.

PMID- 25871115
TI  - Thomson rings in a disk.
AB  - We discuss the basic principles of self-organization of a finite number of
      charged particles interacting via the 1/r Coulomb potential in disk geometry. The
      analysis is based on the cyclic symmetry and periodicity of the Coulomb
      interaction between particles located on several rings. As a result, a system of
      equations is derived, which allows us readily to determine with high accuracy the
      equilibrium configurations of a few hundred charged particles. For n?200, we
      predict the formation of a hexagonal core and valence circular rings for the
      centered configurations. 

PMID- 25871116
TI  - Active microrheology in active matter systems: Mobility, intermittency, and
      avalanches.
AB  - We examine the mobility and velocity fluctuations of a driven particle moving
      through an active matter bath of self-mobile disks for varied density or area
      coverage and varied activity. We show that the driven particle mobility can
      exhibit nonmonotonic behavior that is correlated with distinct changes in the
      spatiotemporal structures that arise in the active media. We demonstrate that the
      probe particle velocity distributions exhibit specific features in the different
      dynamic regimes and identify an activity-induced uniform crystallization that
      occurs for moderate activity levels and is distinct from the previously observed
      higher activity cluster phase. The velocity distribution in the cluster phase has
      telegraph noise characteristics produced when the probe particle moves
      alternately through high-mobility areas that are in the gas state and low
      mobility areas that are in the dense phase. For higher densities and large
      activities, the system enters what we characterize as an active jamming regime.
      Here the probe particle moves in intermittent jumps or avalanches that have power
      law-distributed sizes that are similar to the avalanche distributions observed
      for nonactive disk systems near the jamming transition. 

PMID- 25871117
TI  - Reconstruction of nonstationary disordered materials and media: Watershed
      transform and cross-correlation function.
AB  - Nonstationary disordered materials and media, those for which the probability
      distribution function of any property varies spatially when shifted in space, are
      abundant and encountered in astrophysics, oceanography, air pollution patterns,
      large-scale porous media, biological tissues and organs, and composite materials.
      Their reconstruction and modeling is a notoriously difficult and largely unsolved
      problem. We propose a method for reconstructing a broad class of such media based
      on partitioning them into locally stationary zones. Two methods are used for the
      partitioning. One is based on the Shannon entropy, while the second method
      utilizes a watershed transform. The locally stationary zones are then
      reconstructed based on a cross-correlation function and one-dimensional raster
      path that we recently introduced [P. Tahmasebi and M. Sahimi, Phys. Rev. Lett.
      110, 078002 (2013)], with overlaps between the zones to ensure seamless
      transition from one zone to another. A large number of examples, including porous
      media, ecological systems, disordered materials, and biological tissues and
      organs, are reconstructed and analyzed to demonstrate the accuracy of the method.

PMID- 25871118
TI  - Image-charge forces in thin interlayers due to surface charges in electrolyte.
AB  - The surface forces arising in wetting films of nonpolar liquids or in thin air
      interlayers between an electrolyte and a nonpolar medium in the case of discrete
      charging of the dielectric-electrolyte interface are considered. The
      contributions of polarization effects to the distribution of the electrostatic
      potential in the three contacting media were calculated. Within the Debye-Huckel
      approximation, the analytical solutions were derived for the disjoining pressure
      in thin films, for the case of either dilute or relatively concentrated
      electrolyte solutions in the aforementioned systems. Analysis of the analytical
      and numerical results demonstrated that for dilute solutions the contribution of
      image forces to the disjoining pressure may significantly exceed the van der
      Waals forces for films from a few to tens of nanometers thick. 

PMID- 25871119
TI  - Emergence of step flow from an atomistic scheme of epitaxial growth in 1+1
      dimensions.
AB  - The Burton-Cabrera-Frank (BCF) model for the flow of line defects (steps) on
      crystal surfaces has offered useful insights into nanostructure evolution. This
      model has rested on phenomenological grounds. Our goal is to show via scaling
      arguments the emergence of the BCF theory for noninteracting steps from a
      stochastic atomistic scheme of a kinetic restricted solid-on-solid model in one
      spatial dimension. Our main assumptions are: adsorbed atoms (adatoms) form a
      dilute system, and elastic effects of the crystal lattice are absent. The step
      edge is treated as a front that propagates via probabilistic rules for atom
      attachment and detachment at the step. We formally derive a quasistatic step flow
      description by averaging out the stochastic scheme when terrace diffusion, adatom
      desorption, and deposition from above are present. 

PMID- 25871120
TI  - Analysis of Ginzburg-Landau-type models of surfactant-assisted liquid phase
      separation.
AB  - In this paper diffuse interface models of surfactant-assisted liquid-liquid phase
      separation are addressed. We start from the generalized version of the Ginzburg
      Landau free-energy-functional-based model of van der Sman and van der Graaf.
      First, we analyze the model in the constant surfactant approximation and show the
      presence of a critical point at which the interfacial tension vanishes. Then we
      determine the adsorption isotherms and investigate the validity range of previous
      results. As a key point of the work, we propose a new model of the van der
      Sman/van der Graaf type designed for avoiding both unwanted unphysical effects
      and numerical difficulties present in previous models. In order to make the model
      suitable for describing real systems, we determine the interfacial tension
      analytically more precisely and analyze it over the entire accessible surfactant
      load range. Emerging formulas are then validated by calculating the interfacial
      tension from the numerical solution of the Euler-Lagrange equations. Time
      dependent simulations are also performed to illustrate the slowdown of the phase
      separation near the critical point and to prove that the dynamics of the phase
      separation is driven by the interfacial tension. 

PMID- 25871121
TI  - Structures of simple liquids in contact with nanosculptured surfaces.
AB  - We present a density functional study of Lennard-Jones liquids in contact with a
      nanocorrugated wall. The corresponding substrate potential is taken to exhibit a
      repulsive hard core and a Van der Waals attraction. The corrugation is modeled by
      a periodic array of square nanopits. We have used the modified Rosenfeld density
      functional in order to study the interfacial structure of these liquids which
      with respect to their thermodynamic bulk state are considered to be deep inside
      their liquid phase. We find that already considerably below the packing fraction
      of bulk freezing of these liquids, inside the nanopits a three-dimensional-like
      density localization sets in. If the sizes of the pits are commensurate with the
      packing requirements, we observe high-density spots separated from each other in
      all spatial directions by liquid of comparatively very low density. The number,
      shape, size, and density of these high-density spots depend sensitively on the
      depth and width of the pits. Outside the pits, only layering is observed; above
      the pit openings these layers are distorted with the distortion reaching up to a
      few molecular diameters. We discuss quantitatively how this density localization
      is affected by the geometrical features of the pits and how it evolves upon
      increasing the bulk packing fraction. Our results are transferable to colloidal
      systems and pit dimensions corresponding to several diameters of the colloidal
      particles. For such systems the predicted unfolding of these structural changes
      can be studied experimentally on much larger length scales and more directly
      (e.g., optically) than for molecular fluids which typically call for
      sophisticated x-ray scattering. 

PMID- 25871122
TI  - Spontaneous change in trajectory patterns of a self-propelled oil droplet at the
      air-surfactant solution interface.
AB  - Trajectory-pattern formation of a self-propelled oil droplet floating on the
      surface of a surfactant solution in a circular dish is studied both
      experimentally and by simulation. The Marangoni effect induced by the dissolution
      of oil in the solution drives the droplet's motion. The trajectories
      spontaneously organize into several patterns including circular, knot-forming,
      back-and-forth, and irregular ones. They are either global patterns, whose center
      corresponds to the dish center, or other local patterns. Our simple model
      consisting of three forces, the driving force, the viscous resistance, and the
      repulsion from the boundary, successfully reproduces the global trajectory
      patterns including the power spectrum of the droplet speed. 

PMID- 25871123
TI  - Transition from isometric to stretching ridges in thin elastic films.
AB  - Isometric deformations in thin elastic films easily form ridges to connect large
      flat regions or facets. Depending on the forces applied or the boundary
      conditions imposed, these ridges can be isometric, with no stretching or
      "stretching ridges" when bending and stretching are required to relax the elastic
      energy. Here we study a simple configuration to observe the transition between an
      isometric ridge to the well-known stretching ridge observed in crumpled films,
      and obtain the parameters that determine the ridge type. Specifically, we show
      that the transversal size of a stretching ridge acts as a cutoff length scale: a
      ridge is isometric if its width is greater than this characteristic length. 

PMID- 25871124
TI  - Critical Casimir forces in the presence of random surface fields.
AB  - We study critical Casimir forces (CCFs) fC for films of thickness L which in the
      three-dimensional bulk belong to the Ising universality class and which are
      exposed to random surface fields (RSFs) on both surfaces. We consider the case in
      which, in the absence of RSFs, the surfaces of the film belong to the surface
      universality class of the so-called ordinary transition. We carry out a finite
      size scaling analysis and show that for weak disorder, CCFs still exhibit
      scaling, acquiring a random field scaling variable w that is zero for pure
      systems. We confirm these analytic predictions by Monte Carlo (MC) simulations.
      Moreover, our MC data show that fC varies as fC(w->0)-fC(w=0)~w2. Asymptotically,
      for large L, w scales as w~L-0.26->0, indicating that this type of disorder is an
      irrelevant perturbation of the ordinary surface universality class. However, for
      thin films such that w?1, we find that the presence of RSFs with vanishing mean
      value increases significantly the strength of CCFs, as compared to systems
      without them, and it shifts the extremum of the scaling function of fC toward
      lower temperatures. But fC remains attractive.

PMID- 25871125
TI  - Phase behavior of Langmuir monolayers with ionic molecular heads: Molecular
      simulations.
AB  - We carried out Monte Carlo simulations in the N,Pi,T ensemble of a Langmuir
      monolayer coarse-grained molecular model. Considering that the hydrophilic groups
      can be ionized by modulating acid-base interactions, here we study the phase
      behavior of a model that incorporates the short-range steric and long-range ionic
      interactions. The simulations were carried out in the reduced temperature range
      0.1<=T*<4.0, where there is a competition of these interactions. Different order
      parameters were calculated and analyzed for several values of the reduced surface
      pressure in the interval, 1<=Pi*<=40. For most of the surface pressures two
      directions of molecular tilt were found: (i) towards the nearest neighbor (NN) at
      low temperatures, T*<0.7, and most of the values of Pi* and (ii) towards next
      nearest neighbors (NNN) in the temperature interval 0.7<=T*<1.1 for Pi*<25. We
      also found the coexistence of the NN and NNN at intermediate temperatures and
      Pi*>25. A low-temperature reentrant disorder-order-disorder transition in the
      positions of the molecular heads and in the collective tilt of the tails was
      found for all the surface pressure values. It was also found that the molecular
      tails arranged forming "rotating patterns" in the temperature interval,
      0.5<T*<1.5, at intermediate surface pressures. We estimated the monolayer's
      surface pressure versus temperature and the temperature versus area per molecule
      phase diagrams. It was found that the LE<->LC phase transition shifts to smaller
      temperatures when the molecular heads carry an ion in qualitative agreement with
      experimental observations of fatty acid monolayers with ionic head groups. Two
      surface pressure versus area per molecule isotherms were also calculated. At low
      temperatures near the LC-NN <-> LC-NNN transitions and at higher temperatures
      close to the LE <-> LC transitions. From these isotherms the monolayer's area
      compression modulus was obtained and its variation ranges in the LE and LC phases
      were found to be consistent with the experimental values.

PMID- 25871126
TI  - Crystal-liquid interfacial free energy of hard spheres via a thermodynamic
      integration scheme.
AB  - The hard-sphere crystal-liquid interfacial free energy gammacl is determined from
      molecular dynamics simulations using a thermodynamic integration (TI) scheme. The
      advantage of this TI scheme compared to previous methods is to successfully
      circumvent hysteresis effects due to the movement of the crystal-liquid
      interface. This is accomplished by the use of extremely-short-range and
      impenetrable Gaussian flat walls that prevent the drift of the interface while
      imposing a negligible free-energy penalty. We find that it is crucial to analyze
      finite-size effects in order to obtain reliable estimates of gammacl in the
      thermodynamic limit.

PMID- 25871127
TI  - Tunable dielectric constant of water at the nanoscale.
AB  - Using molecular dynamics simulations, the influence of the surface charge density
      of a nanotube on the static dielectric permittivity epsilon of confined water was
      reported. Whereas the dielectric anisotropy between the radial and axial
      directions of water confined in hydrophilic and hydrophobic membranes and the
      increase in axial dielectric permittivity with respect to the bulk value have
      previously been described, we found that an increase in the surface charge
      density leads to a drastic decrease in epsilon into the axial direction. The
      decrease in epsilon is accompanied by a strong slowdown in the rotational
      dynamics of water molecules. We show that this effect is due to the strong
      orientation of water molecules induced by the surface charge. Thus, by
      controlling the surface charge in nanotubes and nanocavities, it is possible to
      tune the dielectric permittivity of confined fluids at the nanoscale. 

PMID- 25871128
TI  - Plastic deformation of a model glass induced by a local shear transformation.
AB  - The effect of a local shear transformation on plastic deformation of a three
      dimensional amorphous solid is studied using molecular dynamics simulations. We
      consider a spherical inclusion, which is gradually transformed into an ellipsoid
      of the same volume and then converted back into the sphere. It is shown that at
      sufficiently large strain amplitudes, the deformation of the material involves
      localized plastic events that are identified based on the relative displacement
      of atoms before and after the shear transformation. We find that the density
      profiles of cage jumps decay away from the inclusion, which correlates well with
      the radial dependence of the local deformation of the material. At the same
      strain amplitude, the plastic deformation becomes more pronounced in the cases of
      weakly damped dynamics or large time scales of the shear transformation. We show
      that the density profiles can be characterized by the universal function of the
      radial distance multiplied by a dimensionless factor that depends on the friction
      coefficient and the time scale of the shear event. 

PMID- 25871129
TI  - Elastocapillarity can control the formation and the morphology of beads-on-string
      structures in solid fibers.
AB  - Beads-on-string patterns have been experimentally observed in solid cylinders for
      a wide range of material properties and structural lengths, from millimetric soft
      gels to nanometric hard fibers. In this work, we combine theoretical analysis and
      numerical tools to investigate the formation and nonlinear dynamics of such
      beaded structures. We show that this morphological transition is driven by
      elastocapillarity, i.e., a complex interplay between the effects of surface
      tension and bulk elasticity. Unlike buckling or wrinkling, the presence of an
      axial elongation is found here to favor the onset of fiber beading, in agreement
      with existing experimental results on electrospun fibers, hydrogels, and nerves.
      Our results also prove that the applied stretch can be used in fabrication
      techniques to control the morphology of the emerging beads-on-string patterns.
      Such quantitative predictions open the way for several applications, from tissue
      engineering to the design of stretchable electronics and the microfabrication of
      functionalized surfaces. 

PMID- 25871130
TI  - Adsorption-desorption processes of polydisperse mixtures on a triangular lattice.
AB  - Adsorption-desorption processes of polydisperse mixtures on a triangular lattice
      are studied by numerical simulations. Mixtures are composed of the shapes of
      different numbers of segments and rotational symmetries. Numerical simulations
      are performed to determine the influence of the number of mixture components and
      the length of the shapes making the mixture on the kinetics of the deposition
      process. We find that, above the jamming limit, the time evolution of the total
      coverage of a mixture can be described by the Mittag-Leffler function
      theta(t)=thetainfinity-DeltathetaE[-(t/tau)beta] for all the mixtures we have
      examined. Our results show that the equilibrium coverage decreases with the
      number of components making the mixture and also with the desorption probability,
      via corresponding stretched exponential laws. For the mixtures of equal-sized
      objects, we propose a simple formula for predicting the value of the steady-state
      coverage fraction of a mixture from the values of the steady-state coverage
      fractions of pure component shapes.

PMID- 25871131
TI  - Nonlinear fluctuation effects in dynamics of freely suspended films.
AB  - Long-scale dynamic fluctuation phenomena in freely suspended films is analyzed.
      We consider isotropic films that, say, can be pulled from bulk smectic-A liquid
      crystals. The key feature of such objects is possibility of bending deformations
      of the film. The bending (also known as flexular) mode turns out to be
      anomalously weakly attenuated. In the harmonic approximation there is no viscous
      like damping of the bending mode, proportional to q2 (q is the wave vector of the
      mode), since it is forbidden by the rotational symmetry. Therefore, the bending
      mode is strongly affected by nonlinear dynamic fluctuation effects. We calculate
      the dominant fluctuation contributions to the damping of the bending mode due to
      its coupling to the inplane viscous mode, which restores the viscous-like q^{2}
      damping of the bending mode. Our calculations are performed in the framework of
      the perturbation theory where the coupling of the modes is assumed to be small,
      then the bending mode damping is relatively weak. We discuss our results in the
      context of existing experiments and numeric simulations of the freely suspended
      films and propose possible experimental observations of our predictions.

PMID- 25871132
TI  - Polar structure of disclination loops in nematic liquid crystals probed by second
      harmonic-light scattering.
AB  - Angle-resolved, second-harmonic-light scattering (SHLS) measurements are reported
      for three different classes of thermotropic nematic liquid crystals (NLCs): polar
      and nonpolar rodlike compounds and a bent-core compound. Results revealing well
      defined scattering peaks are interpreted in terms of the electric polarization
      induced by distortions of the nematic orientational field ("flexopolarity")
      associated with inversion wall defects, nonsingular disclinations, analogous to
      Neel walls in ferromagnets, that often exhibit a closed loop morphology in NLCs.
      Analysis of the SHLS patterns based on this model provides a "proof-of-concept"
      for a potentially useful method to probe the flexopolar properties of NLCs. 

PMID- 25871133
TI  - Lehmann rotation of cholesteric droplets: Role of the sample thickness and of the
      concentration of chiral molecules.
AB  - We study the role of the sample thickness d and of the concentration C of chiral
      molecules during the Lehmann rotation of cholesteric droplets of radius R
      subjected to a temperature gradient G->. Two configurations are studied depending
      on how the helix is oriented with respect to G->. The first result is that, at
      fixed C and R, the rotation velocity omega increases with d when the helix is
      parallel to G->, whereas it is independent of d when the helix is perpendicular
      to G->. The second result is that, for a given C,omega0=limR->0omega(R) is the
      same for the two types of droplets independently of d. This suggests that the, as
      yet unknown, physical mechanism responsible for the droplet rotation is the same
      in the two types of droplets. The third result is that the Lehmann coefficient
      nu[over -] defined from the Leslie-like relation omega0= G-G/gamma1 (with gamma_1
      the rotational viscosity) is proportional to the equilibrium twist q. Last, but
      not least, the ratio R-=nu -/q depends on the liquid crystal chosen but is
      independent of the chiral molecule used to dope the liquid crystal.

PMID- 25871134
TI  - Effect of hockey-stick-shaped molecules on the critical behavior at the nematic
      to isotropic and smectic-A to nematic phase transitions in octylcyanobiphenyl.
AB  - In the field of soft matter research, the characteristic behavior of both nematic
      isotropic (N-I) and smectic-A nematic(Sm-A N) phase transitions has gained
      considerable attention due to their several attractive features. In this work, a
      high-resolution measurement of optical birefringence (Deltan) has been performed
      to probe the critical behavior at the N-I and Sm-A N phase transitions in a
      binary system comprising the rodlike octylcyanobiphenyl and a laterally methyl
      substituted hockey-stick-shaped mesogen, 4-(3-n-decyloxy-2-methyl
      phenyliminomethyl)phenyl 4-n-dodecyloxycinnamate. For the investigated mixtures,
      the critical exponent beta related to the limiting behavior of the nematic order
      parameter close to the N-I phase transition has come out to be in good conformity
      with the tricritical hypothesis. Moreover, the yielded effective critical
      exponents (alpha', beta', gamma') characterizing the critical fluctuation near
      the Sm-A N phase transition have appeared to be nonuniversal in nature. With
      increasing hockey-stick-shaped dopant concentration, the Sm-A N phase transition
      demonstrates a strong tendency to be driven towards a first-order nature. Such a
      behavior has been accounted for by considering a modification of the effective
      intermolecular interactions and hence the related coupling between the nematic
      and smectic order parameters, caused by the introduction of the angular mesogenic
      molecules.

PMID- 25871135
TI  - Phase transition and winding properties of a flexible polymer adsorbed to a rigid
      perioidic copolymer.
AB  - Motivated by the noncovalent binding of polypeptides to DNA, the adsorption of a
      flexible polymer to a rigid periodic copolymer is studied in two dimensions and
      three dimensions. The fraction of adsorbed monomers, the specific heat, and the
      Binder cumulant are analyzed and compared with analytical results for an ideal
      chain. As the interaction strength epsilon increases, a second-order phase
      transition occurs from a nonadsorbed state to an adsorbed state, in two
      dimensions, and a higher-order transition occurs in three dimensions. The
      transition point is estimated as epsilon0~2.2 for d=2 and epsilon0~2.1 for d=3,
      where epsilon is given in units of kBT. The dependence of the number of adsorbed
      monomers Nads on the chain length L of the flexible polymer shows a power law
      scaling relation Nads~Lphi, with phi~0.46,0.42 for d=2,3, respectively. We also
      find an optimal epsilon~2.8 for the winding of the flexible polymer around the
      rigid one in three dimensions. Compared to the adsorbed monomers, the successive
      nonadsorbed monomers contribute more to the winding. When the interaction is
      strong, epsilon>3.5, the winding value or the number of winding turns of the
      flexible polymer becomes linearly dependent on the chain length.

PMID- 25871136
TI  - Hierarchical self-assembly: Self-organized nanostructures in a nematically
      ordered matrix of self-assembled polymeric chains.
AB  - We report many different nanostructures which are formed when model nanoparticles
      of different sizes (diameter sigman) are allowed to aggregate in a background
      matrix of semiflexible self-assembled polymeric wormlike micellar chains. The
      different nanostructures are formed by the dynamical arrest of phase-separating
      mixtures of micellar monomers and nanoparticles. The different morphologies
      obtained are the result of an interplay of the available free volume, the elastic
      energy of deformation of polymers, the density (chemical potential) of the
      nanoparticles in the polymer matrix, and, of course, the ratio of the size of
      self-assembling nanoparticles and self-avoidance diameter of polymeric chains. We
      have used a hybrid semi-grand-canonical Monte Carlo simulation scheme to obtain
      the (nonequilibrium) phase diagram of the self-assembled nanostructures. We
      observe rodlike structures of nanoparticles which get self-assembled in the gaps
      between the nematically ordered chains, as well as percolating gel-like network
      of conjoined nanotubes. We also find a totally unexpected interlocked crystalline
      phase of nanoparticles and monomers, in which each crystal plane of nanoparticles
      is separated by planes of perfectly organized polymer chains. We identified the
      condition which leads to such interlocked crystal structure. We suggest
      experimental possibilities of how the results presented in this paper could be
      used to obtain different nanostructures in the laboratory.

PMID- 25871137
TI  - Energy dissipation and recovery in a simple model with reversible cross-links.
AB  - Reversible cross-linking is a method of enhancing the mechanical properties of
      polymeric materials. The inspiration for this kind of cross-linking comes from
      nature, which uses this strategy in a large variety of biological materials to
      dramatically increase their toughness. Recently, first attempts were made to
      transfer this principle to technological applications. In this study, Monte Carlo
      simulations are used to investigate the effect of the number and the topology of
      reversible cross-links on the mechanical performance of a simple model system.
      Computational cyclic loading tests are performed, and the work to fracture and
      the energy dissipation per cycle are determined, which both increase when the
      density of cross-links is increased. Furthermore, a different topology of the
      bonds may increase the work to fracture by a factor of more than 2 for the same
      density. This dependence of the mechanical properties on the topology of the
      bonds has important implications on the self-healing properties of such systems,
      because only a fast return of the system to its unloaded state after release of
      the load ensures that the optimal topology may form. 

PMID- 25871138
TI  - Artificial phosphorylation sites modulate the activity of a voltage-gated
      potassium channel.
AB  - The KvAP potassium channel is representative of a family of voltage-gated ion
      channels where the membrane potential is sensed by a transmembrane helix
      containing several positively charged arginines. Previous work by Wang and Zocchi
      [A. Wang and G. Zocchi, PLoS ONE 6, e18598 (2011)] showed how a negatively
      charged polyelectrolyte attached in proximity to the voltage sensing element can
      bias the opening probability of the channel. Here we introduce three
      phosphorylation sites at the same location and show that the response curve of
      the channel shifts by about 20 mV upon phosphorylation, while other
      characteristics such as the single-channel conductance are unaffected. In
      summary, we construct an artificial phosphorylation site which confers allosteric
      regulation to the channel.

PMID- 25871139
TI  - Mechanisms responsible for the photocurrent in bacteriorhodopsin.
AB  - Recently, there has been growing interest in the electrical properties of
      bacteriorhodopsin (bR), a protein belonging to the transmembrane protein family.
      Several experiments pointed out the role of green light in enhancing the current
      flow in nanolayers of bR, thus confirming potential applications of this protein
      in the field of optoelectronics. By contrast, the mechanisms underlying the
      charge transfer and the associated photocurrent are still far from being
      understood at a microscopic level. To take into account the structure-dependent
      nature of the current, in a previous set of papers we suggested a mechanism of
      sequential tunneling among neighboring amino acids. As a matter of fact, when
      irradiated with green light, bR undergoes a conformational change at a molecular
      level. Thus, the role played by the protein tertiary-structure in modeling the
      charge transfer cannot be neglected. The aim of this paper is to go beyond
      previous models, in the framework of a new branch of electronics we call
      proteotronics, which exploits the ability of using proteins as reliable, well
      understood materials for the development of novel bioelectronic devices. In
      particular, the present approach assumes that the conformational change is not
      the unique transformation the protein undergoes when irradiated by light.
      Instead, the light can also promote an increase of the protein state free energy
      that, in turn, should modify its internal degree of connectivity. This phenomenon
      is here described by the change of the value of an interaction radius associated
      with the physical interactions among amino acids. The implemented model enables
      us to achieve a better agreement between theory and experiments in the region of
      a low applied bias by preserving the level of agreement at high values of applied
      bias. Furthermore, results provide new insights on the mechanisms responsible for
      bR photoresponse. 

PMID- 25871140
TI  - Spatial spread of the Hantavirus infection.
AB  - The spatial propagation of Hantavirus-infected mice is considered a serious
      threat for public health. We analyze the spatial spread of the infected mice by
      including diffusion in the stage-dependent model for Hantavirus infection
      recently proposed by Reinoso and de la Rubia [Phys. Rev. E 87, 042706 (2013)]. We
      consider a general scenario in which mice propagate in fronts from their refugia
      to the surroundings and find an expression for the speed of the front of infected
      mice. We also introduce a depletion time that measures the time scale for an
      appreciable impoverishment of the environment conditions and show how this new
      situation may change the spreading of the infection significantly.

PMID- 25871141
TI  - Quantum decoherence time scales for ionic superposition states in ion channels.
AB  - There are many controversial and challenging discussions about quantum effects in
      microscopic structures in neurons of the brain and their role in cognitive
      processing. In this paper, we focus on a small, nanoscale part of ion channels
      which is called the "selectivity filter" and plays a key role in the operation of
      an ion channel. Our results for superposition states of potassium ions indicate
      that decoherence times are of the order of picoseconds. This decoherence time is
      not long enough for cognitive processing in the brain, however, it may be
      adequate for quantum superposition states of ions in the filter to leave their
      quantum traces on the selectivity filter and action potentials. 

PMID- 25871142
TI  - Error catastrophe and phase transition in the empirical fitness landscape of HIV.
AB  - We have translated clinical sequence databases of the p6 HIV protein into an
      empirical fitness landscape quantifying viral replicative capacity as a function
      of the amino acid sequence. We show that the viral population resides close to a
      phase transition in sequence space corresponding to an "error catastrophe" beyond
      which there is lethal accumulation of mutations. Our model predicts that the
      phase transition may be induced by drug therapies that elevate the mutation rate,
      or by forcing mutations at particular amino acids. Applying immune pressure to
      any combination of killer T-cell targets cannot induce the transition, providing
      a rationale for why the viral protein can exist close to the error catastrophe
      without sustaining fatal fitness penalties due to adaptive immunity. 

PMID- 25871143
TI  - Collective dynamics of soft active particles.
AB  - We present a model of soft active particles that leads to a rich array of
      collective behavior found also in dense biological swarms of bacteria and other
      unicellular organisms. Our model uses only local interactions, such as Vicsek
      type nearest-neighbor alignment, short-range repulsion, and a local boundary
      term. Changing the relative strength of these interactions leads to migrating
      swarms, rotating swarms, and jammed swarms, as well as swarms that exhibit run
      and-tumble motion, alternating between migration and either rotating or jammed
      states. Interestingly, although a migrating swarm moves slower than an individual
      particle, the diffusion constant can be up to three orders of magnitude larger,
      suggesting that collective motion can be highly advantageous, for example, when
      searching for food. 

PMID- 25871144
TI  - Free induction decay caused by a dipole field.
AB  - We analyze the free induction decay of nuclear spins under the influence of
      restricted diffusion in a magnetic dipole field around cylindrical objects. In
      contrast to previous publications no restrictions or simplifications concerning
      the diffusion process are made. By directly solving the Bloch-Torrey equation,
      analytical expressions for the magnetization are given in terms of an
      eigenfunction expansion. The field strength-dependent complex nature of the
      eigenvalue spectrum significantly influences the shape of the free induction
      decay. As the dipole field is the lowest order of the multipole expansion, the
      obtained results are important for understanding fundamental mechanisms of spin
      dephasing in many other applied fields of nuclear magnetic resonance such as
      biophysics or material science. The analytical methods are applied to interpret
      the spin dephasing in the free induction decay in cardiac muscle and skeletal
      muscle. A simple expression for the relevant transverse relaxation time is found
      in terms of the underlying microscopic parameters of the muscle tissue. The
      analytical results are in agreement with experimental data. These findings are
      important for the correct interpretation of magnetic resonance images for
      clinical diagnosis at all magnetic field strengths and therapy of cardiovascular
      diseases. 

PMID- 25871145
TI  - Channel-noise-induced critical slowing in the subthreshold Hodgkin-Huxley neuron.
AB  - The dynamics of a spiking neuron approaching threshold is investigated in the
      framework of Markov-chain models describing the random state-transitions of the
      underlying ion-channel proteins. We characterize subthreshold channel-noise
      induced transmembrane potential fluctuations in both type-I (integrator) and type
      II (resonator) parametrizations of the classic conductance-based Hodgkin-Huxley
      equations. As each neuron approaches spiking threshold from below, numerical
      simulations of stochastic trajectories demonstrate pronounced growth in amplitude
      simultaneous with decay in frequency of membrane voltage fluctuations induced by
      ion-channel state transitions. To explore this progression of fluctuation
      statistics, we approximate the exact Markov treatment with a 12-variable channel
      based stochastic differential equation (SDE) and its Ornstein-Uhlenbeck (OU)
      linearization and show excellent agreement between Markov and SDE numerical
      simulations. Predictions of the OU theory with respect to membrane potential
      fluctuation variance, autocorrelation, correlation time, and spectral density are
      also in agreement and illustrate the close connection between the eigenvalue
      structure of the associated deterministic bifurcations and the observed behavior
      of the noisy Markov traces on close approach to threshold for both integrator and
      resonator point-neuron varieties. 

PMID- 25871146
TI  - Unusual specific heat of almost dry L-cysteine and L-cystine amino acids.
AB  - A detailed quantitative analysis of the specific heat in the 0.5- to 200-K
      temperature range for almost dry L-cysteine and its dimer, L-cystine, amino acids
      is presented. We report the occurrence of a sharp first-order transition at ~76 K
      for L-cysteine associated with the thiol group ordering which was successfully
      modeled with the two-dimensional Ising model. We demonstrated that quantum
      rotors, two-level systems (TLS), Einstein oscillators, and acoustic phonons (the
      Debye model) are essential ingredients to correctly describe the overall
      experimental data. Our analysis pointed out the absence of the TLS contribution
      to the low temperature specific heat of L-cysteine. This result was similar to
      that found in other noncrystalline amorphous materials, e.g., amorphous silicon,
      low density amorphous water, and ultrastable glasses. L-cystine presented an
      unusual nonlinear acoustic dispersion relation omega(q)=vq0.95 and a Maxwell
      Boltzmann-type distribution of tunneling barriers. The presence of Einstein
      oscillators with ThetaE~70 K was common in both systems and adequately modeled
      the boson peak contributions.

PMID- 25871147
TI  - Role of side-chain interactions on the formation of alpha-helices in model
      peptides.
AB  - The role played by side-chain interactions on the formation of alpha-helices is
      studied using extensive all-atom molecular dynamics simulations of polyalanine
      like peptides in explicit TIP4P water. The peptide is described by the OPLS-AA
      force field except for the Lennard-Jones interaction between Cbeta-Cbeta atoms,
      which is modified systematically. We identify values of the Lennard-Jones
      parameter that promote alpha-helix formation. To rationalize these results,
      potentials of mean force (PMF) between methane-like molecules that mimic side
      chains in our polyalanine-like peptides are computed. These PMF exhibit a complex
      distance dependence where global and local minima are separated by an energy
      barrier. We show that alpha-helix propensity correlates with values of these PMF
      at distances corresponding to Cbeta-Cbeta of i-i+3 and other nearest neighbors in
      the alpha-helix. In particular, the set of Lennard-Jones parameters that promote
      alpha-helices is characterized by PMF that exhibit a global minimum at distances
      corresponding to i-i+3 neighbors in alpha-helices. Implications of these results
      are discussed.

PMID- 25871148
TI  - Stationary solutions for metapopulation Moran models with mutation and selection.
AB  - We construct an individual-based metapopulation model of population genetics
      featuring migration, mutation, selection, and genetic drift. In the case of a
      single "island," the model reduces to the Moran model. Using the diffusion
      approximation and time-scale separation arguments, an effective one-variable
      description of the model is developed. The effective description bears
      similarities to the well-mixed Moran model with effective parameters that depend
      on the network structure and island sizes, and it is amenable to analysis.
      Predictions from the reduced theory match the results from stochastic simulations
      across a range of parameters. The nature of the fast-variable elimination
      technique we adopt is further studied by applying it to a linear system, where it
      provides a precise description of the slow dynamics in the limit of large time
      scale separation. 

PMID- 25871149
TI  - Atomic torsional modal analysis for high-resolution proteins.
AB  - We introduce a formulation for normal mode analyses of globular proteins that
      significantly improves on an earlier one-parameter formulation [M. M. Tirion,
      Phys. Rev. Lett. 77, 1905 (1996)] that characterized the slow modes associated
      with protein data bank structures. Here we develop that empirical potential
      function that is minimized at the outset to include two features essential to
      reproduce the eigenspectra and associated density of states in the 0 to 300cm-1
      frequency range, not merely the slow modes. First, introduction of preferred
      dihedral-angle configurations via use of torsional stiffness constants eliminates
      anomalous dispersion characteristics due to insufficiently bound surface side
      chains and helps fix the spectrum thin tail frequencies (100-300cm-1). Second, we
      take into account the atomic identities and the distance of separation of all
      pairwise interactions, improving the spectrum distribution in the 20 to 300cm-1
      range. With these modifications, not only does the spectrum reproduce that of
      full atomic potentials, but we obtain stable reliable eigenmodes for the slow
      modes and over a wide range of frequencies.

PMID- 25871150
TI  - Domain nucleation and confinement in agent-controlled bistable systems.
AB  - We report a mechanism of pattern formation in growing bistable systems coupled
      indirectly. A modified Fujita et al. model is studied as an example of a reaction
      diffusion system of nondiffusive activator and inhibitor molecules immersed in
      the medium of a fast diffusive agent. Here we show that, as the system grows, a
      new domain nucleates spontaneously in the area where the local level of the agent
      becomes critical. Newly nucleated domains are stable and the pattern formation is
      different from Turing's mechanism in monostable systems. Domains are spatially
      confined by the agent even if the activator and inhibitor molecules diffuse. With
      the spatial extension of the system, a larger domain may undergo a wave number
      instability, and the concentrations of active molecules within the neighboring
      elements of a domain can become sharply different. The mechanism reported in this
      work could be generic for pattern formation systems involving multistability,
      growth, and indirect coupling. 

PMID- 25871151
TI  - Diffusion-limited encounter rate in a three-dimensional lattice of connected
      compartments studied by Brownian-dynamics simulations.
AB  - We considered the rate at which a diffusing particle encounters a target in a
      three-dimensional lattice of compartments with semipermeable walls. This work
      expands a previous theory [Li et al., Phys. Rev. Lett. 113, 028303 (2014)] for
      the encounter rate in the dilute limit of targets to the general case of any
      density of targets. We also used Brownian dynamics simulations to evaluate the
      approximations in the analytical theory. We find that the largest errors in the
      analytical theory are on the order of 10%. This work therefore demonstrates an
      analytical theory capable of describing the encounter rates in compartmentalized
      environments for any level of confinement and any target density.

PMID- 25871152
TI  - Structure of attractors in randomly connected networks.
AB  - The deterministic dynamics of randomly connected neural networks are studied,
      where a state of binary neurons evolves according to a discrete-time synchronous
      update rule. We give theoretical support that the overlap of systems' states
      between the current and a previous time develops in time according to a Markovian
      stochastic process in large networks. This Markovian process predicts how often a
      network revisits one of the previously visited states, depending on the system
      size. The state concentration probability, i.e., the probability that two
      distinct states coevolve to the same state, is utilized to analytically derive
      various characteristics that quantify attractors' structure. The analytical
      predictions about the total number of attractors, the typical cycle length, and
      the number of states belonging to all attractive cycles match well with numerical
      simulations for relatively large system sizes. 

PMID- 25871153
TI  - Identification of core-periphery structure in networks.
AB  - Many networks can be usefully decomposed into a dense core plus an outlying,
      loosely connected periphery. Here we propose an algorithm for performing such a
      decomposition on empirical network data using methods of statistical inference.
      Our method fits a generative model of core-periphery structure to observed data
      using a combination of an expectation-maximization algorithm for calculating the
      parameters of the model and a belief propagation algorithm for calculating the
      decomposition itself. We find the method to be efficient, scaling easily to
      networks with a million or more nodes, and we test it on a range of networks,
      including real-world examples as well as computer-generated benchmarks, for which
      it successfully identifies known core-periphery structure with low error rate. We
      also demonstrate that the method is immune to the detectability transition
      observed in the related community detection problem, which prevents the detection
      of community structure when that structure is too weak. There is no such
      transition for core-periphery structure, which is detectable, albeit with some
      statistical error, no matter how weak it is. 

PMID- 25871154
TI  - Universal phase transition in community detectability under a stochastic block
      model.
AB  - We prove the existence of an asymptotic phase-transition threshold on community
      detectability for the spectral modularity method [M. E. J. Newman, Phys. Rev. E
      74, 036104 (2006) and Proc. Natl. Acad. Sci. (USA) 103, 8577 (2006)] under a
      stochastic block model. The phase transition on community detectability occurs as
      the intercommunity edge connection probability p grows. This phase transition
      separates a subcritical regime of small p, where modularity-based community
      detection successfully identifies the communities, from a supercritical regime of
      large p where successful community detection is impossible. We show that, as the
      community sizes become large, the asymptotic phase-transition threshold p* is
      equal to ?[p1p2], where pi(i=1,2) is the within-community edge connection
      probability. Thus the phase-transition threshold is universal in the sense that
      it does not depend on the ratio of community sizes. The universal phase
      transition phenomenon is validated by simulations for moderately sized
      communities. Using the derived expression for the phase-transition threshold, we
      propose an empirical method for estimating this threshold from real-world data.

PMID- 25871155
TI  - Percolation on networks with antagonistic and dependent interactions.
AB  - Drawing inspiration from real world interacting systems, we study a system
      consisting of two networks that exhibit antagonistic and dependent interactions.
      By antagonistic and dependent interactions we mean that a proportion of
      functional nodes in a network cause failure of nodes in the other, while failure
      of nodes in the other results in failure of links in the first. In contrast to
      interdependent networks, which can exhibit first-order phase transitions, we find
      that the phase transitions in such networks are continuous. Our analysis shows
      that, compared to an isolated network, the system is more robust against random
      attacks. Surprisingly, we observe a region in the parameter space where the giant
      connected components of both networks start oscillating. Furthermore, we find
      that for Erdos-Renyi and scale-free networks the system oscillates only when the
      dependence and antagonism between the two networks are very high. We believe that
      this study can further our understanding of real world interacting systems. 

PMID- 25871156
TI  - Significance of trends in long-term correlated records.
AB  - We study the distribution P(x;alpha,L) of the relative trend x in long-term
      correlated records of length L that are characterized by a Hurst exponent alpha
      between 0.5 and 1.5. The relative trend x is the ratio between the strength of
      the trend Delta in the record measured by linear regression and the standard
      deviation sigma around the regression line. We consider L between 400 and 2200,
      which is the typical length scale of monthly local and annual reconstructed
      global climate records. Extending previous work by Lennartz and Bunde [S.
      Lennartz and A. Bunde, Phys. Rev. E 84, 021129 (2011)] we show explicitly that x
      follows the Student's t distribution P?[1+(x/a)2/l]-(l+1)/2, where the scaling
      parameter a depends on both L and alpha, while the effective length l depends,
      for alpha below 1.15, only on the record length L. From P we can derive an
      analytical expression for the trend significance S(x;alpha,L)=?(
      x)xP(x';alpha,L)dx' and the border lines of the 95% significance interval. We
      show that the results are nearly independent of the distribution of the data in
      the record, holding for Gaussian data as well as for highly skewed non-Gaussian
      data. For an application, we use our methodology to estimate the significance of
      central west Antarctic warming.

PMID- 25871157
TI  - Impact of imperfect information on network attack.
AB  - This paper explores the effectiveness of network attack when the attacker has
      imperfect information about the network. For Erdos-Renyi networks, we observe
      that dynamical importance and betweenness centrality-based attacks are
      surprisingly robust to the presence of a moderate amount of imperfect information
      and are more effective compared with simpler degree-based attacks even at
      moderate levels of network information error. In contrast, for scale-free
      networks the effectiveness of attack is much less degraded by a moderate level of
      information error. Furthermore, in the Erdos-Renyi case the effectiveness of
      network attack is much more degraded by missing links as compared with the same
      number of false links. 

PMID- 25871158
TI  - Entropic determination of the phase transition in a coevolving opinion-formation
      model.
AB  - We study an opinion formation model by the means of a coevolving complex network
      where the vertices represent the individuals, characterized by their evolving
      opinions, and the edges represent the interactions among them. The network adapts
      to the spreading of opinions in two ways: not only connected agents interact and
      eventually change their thinking but an agent may also rewire one of its links to
      a neighborhood holding the same opinion as his. The dynamics, based on a global
      majority rule, depends on an external parameter that controls the plasticity of
      the network. We show how the information entropy associated to the distribution
      of group sizes allows us to locate the phase transition between a phase of full
      consensus and another, where different opinions coexist. We also determine the
      minimum size of the most informative sampling. At the transition the distribution
      of the sizes of groups holding the same opinion is scale free. 

PMID- 25871159
TI  - Social diffusion and global drift on networks.
AB  - We study a mathematical model of social diffusion on a symmetric weighted network
      where individual nodes' states gradually assimilate to local social norms made by
      their neighbors' average states. Unlike physical diffusion, this process is not
      state conservational and thus the global state of the network (i.e., sum of node
      states) will drift. The asymptotic average node state will be the average of
      initial node states weighted by their strengths. Here we show that, while the
      global state is not conserved in this process, the inner product of strength and
      state vectors is conserved instead, and perfect positive correlation between node
      states and local averages of their self-neighbor strength ratios always results
      in upward (or at least neutral) global drift. We also show that the strength
      assortativity negatively affects the speed of homogenization. Based on these
      findings, we propose an adaptive link weight adjustment method to achieve the
      highest upward global drift by increasing the strength-state correlation. The
      effectiveness of the method was confirmed through numerical simulations and
      implications for real-world social applications are discussed. 

PMID- 25871160
TI  - Modeling the average shortest-path length in growth of word-adjacency networks.
AB  - We investigate properties of evolving linguistic networks defined by the word
      adjacency relation. Such networks belong to the category of networks with
      accelerated growth but their shortest-path length appears to reveal the network
      size dependence of different functional form than the ones known so far. We thus
      compare the networks created from literary texts with their artificial
      substitutes based on different variants of the Dorogovtsev-Mendes model and
      observe that none of them is able to properly simulate the novel asymptotics of
      the shortest-path length. Then, we identify the local chainlike linear growth
      induced by grammar and style as a missing element in this model and extend it by
      incorporating such effects. It is in this way that a satisfactory agreement with
      the empirical result is obtained. 

PMID- 25871161
TI  - Effects of degree correlations on the explosive synchronization of scale-free
      networks.
AB  - We study the organization of finite-size, large ensembles of phase oscillators
      networking via scale-free topologies in the presence of a positive correlation
      between the oscillators' natural frequencies and the network's degrees. Under
      those circumstances, abrupt transitions to synchronization are known to occur in
      growing scale-free networks, while the transition has a completely different
      nature for static random configurations preserving the same structure-dynamics
      correlation. We show that the further presence of degree-degree correlations in
      the network structure has important consequences on the nature of the phase
      transition characterizing the passage from the phase-incoherent to the phase
      coherent network state. While high levels of positive and negative mixing
      consistently induce a second-order phase transition, moderate values of
      assortative mixing, such as those ubiquitously characterizing social networks in
      the real world, greatly enhance the irreversible nature of explosive
      synchronization in scale-free networks. The latter effect corresponds to a
      maximization of the area and of the width of the hysteretic loop that
      differentiates the forward and backward transitions to synchronization. 

PMID- 25871162
TI  - Accuracy criterion for the mean-field approximation in susceptible-infected
      susceptible epidemics on networks.
AB  - Mean-field approximations (MFAs) are frequently used in physics. When a process
      (such as an epidemic or a synchronization) on a network is approximated by MFA, a
      major hurdle is the determination of those graphs for which MFA is reasonably
      accurate. Here, we present an accuracy criterion for Markovian susceptible
      infected-susceptible (SIS) epidemics on any network, based on the spectrum of the
      adjacency and SIS covariance matrix. We evaluate the MFA criterion for the
      complete and star graphs analytically, and numerically for connected Erdos-Renyi
      random graphs for small size N<=14. The accuracy of MFA increases with average
      degree and with N. Precise simulations (up to network sizes N=100) of the MFA
      accuracy criterion versus N for the complete graph, star, square lattice, and
      path graphs lead us to conjecture that the worst MFA accuracy decreases, for
      large N, proportionally to the inverse of the spectral radius of the adjacency
      matrix of the graph. 

PMID- 25871164
TI  - Critical behavior of the relaxation rate, the susceptibility, and a pair
      correlation function in the Kuramoto model on scale-free networks.
AB  - We study the impact of network heterogeneity on relaxation dynamics of the
      Kuramoto model on uncorrelated complex networks with scale-free degree
      distributions. Using the Ott-Antonsen method and the annealed-network approach,
      we find that the critical behavior of the relaxation rate near the
      synchronization phase transition does not depend on network heterogeneity and
      critical slowing down takes place at the critical point when the second moment of
      the degree distribution is finite. In the case of a complete graph we obtain an
      explicit result for the relaxation rate when the distribution of natural
      frequencies is Lorentzian. We also find a response of the Kuramoto model to an
      external field and show that the susceptibility of the model is inversely
      proportional to the relaxation rate. We reveal that network heterogeneity
      strongly impacts a field dependence of the relaxation rate and the susceptibility
      when the network has a divergent fourth moment of degree distribution. We
      introduce a pair correlation function of phase oscillators and show that it has a
      sharp peak at the critical point, signaling emergence of long-range correlations.
      Our numerical simulations of the Kuramoto model support our analytical results. 

PMID- 25871163
TI  - Synchronization properties of heterogeneous neuronal networks with mixed
      excitability type.
AB  - We study the synchronization of neuronal networks with dynamical heterogeneity,
      showing that network structures with the same propensity for synchronization (as
      quantified by master stability function analysis) may develop dramatically
      different synchronization properties when heterogeneity is introduced with
      respect to neuronal excitability type. Specifically, we investigate networks
      composed of neurons with different types of phase response curves (PRCs), which
      characterize how oscillating neurons respond to excitatory perturbations. Neurons
      exhibiting type 1 PRC respond exclusively with phase advances, while neurons
      exhibiting type 2 PRC respond with either phase delays or phase advances,
      depending on when the perturbation occurs. We find that Watts-Strogatz small
      world networks transition to synchronization gradually as the proportion of type
      2 neurons increases, whereas scale-free networks may transition gradually or
      rapidly, depending upon local correlations between node degree and excitability
      type. Random placement of type 2 neurons results in gradual transition to
      synchronization, whereas placement of type 2 neurons as hubs leads to a much more
      rapid transition, showing that type 2 hub cells easily "hijack" neuronal networks
      to synchronization. These results underscore the fact that the degree of
      synchronization observed in neuronal networks is determined by a complex
      interplay between network structure and the dynamical properties of individual
      neurons, indicating that efforts to recover structural connectivity from
      dynamical correlations must in general take both factors into account. 

PMID- 25871165
TI  - Long-range epidemic spreading in a random environment.
AB  - Modeling long-range epidemic spreading in a random environment, we consider a
      quenched, disordered, d-dimensional contact process with infection rates decaying
      with distance as 1/rd+sigma. We study the dynamical behavior of the model at and
      below the epidemic threshold by a variant of the strong-disorder renormalization
      group method and by Monte Carlo simulations in one and two spatial dimensions.
      Starting from a single infected site, the average survival probability is found
      to decay as P(t)~t-d/z up to multiplicative logarithmic corrections. Below the
      epidemic threshold, a Griffiths phase emerges, where the dynamical exponent z
      varies continuously with the control parameter and tends to zc=d+sigma as the
      threshold is approached. At the threshold, the spatial extension of the infected
      cluster (in surviving trials) is found to grow as R(t)~t1/zc with a
      multiplicative logarithmic correction and the average number of infected sites in
      surviving trials is found to increase as Ns(t)~(lnt)chi with chi=2 in one
      dimension.

PMID- 25871166
TI  - Chaos in kicked ratchets.
AB  - We present a minimal one-dimensional deterministic continuous dynamical system
      that exhibits chaotic behavior and complex transport properties. Our model is an
      overdamped rocking ratchet with finite dissipation, that is periodically kicked
      with a delta function driving force, without finite inertia terms or temporal or
      spatial stochastic forces. To our knowledge this is the simplest model reported
      in the literature for a ratchet, with this complex behavior. We develop an
      analytical approach that predicts many key features of the system, such as
      current reversals, as well as the presence of chaotic behavior and bifurcation.
      Our analytical approach allows us to study the transition from regular to chaotic
      motion as well as a tangent bifurcation associated with this transition. We show
      that our approach can be easily extended to other types of periodic driving
      forces. The square wave is shown as an example. 

PMID- 25871167
TI  - Synchronization of intermittent behavior in ensembles of multistable dynamical
      systems.
AB  - We propose a methodology to analyze synchronization in an ensemble of diffusively
      coupled multistable systems. First, we study how two bidirectionally coupled
      multistable oscillators synchronize and demonstrate the high complexity of the
      basins of attraction of coexisting synchronous states. Then, we propose the use
      of the master stability function (MSF) for multistable systems to describe
      synchronizability, even during intermittent behavior, of a network of multistable
      oscillators, regardless of both the number of coupled oscillators and the
      interaction structure. In particular, we show that a network of multistable
      elements is synchronizable for a given range of topology spectra and coupling
      strengths, irrespective of specific attractor dynamics to which different
      oscillators are locked, and even in the presence of intermittency. Finally, we
      experimentally demonstrate the feasibility and robustness of the MSF approach
      with a network of multistable electronic circuits. 

PMID- 25871168
TI  - Rotation of a scroll wave reveals the metric tensor for the associated geodesic
      filament.
AB  - This study considers a reaction-diffusion medium that supports a rotating scroll
      wave with stationary filament and diffusivity matrix D. The filament is a
      geodesic curve in three-space. The metric tensor g associated with that geodesic
      is obtained in terms of D, resulting in g=(detD)D-1. Here detD (the determinant
      of D) is not necessarily constant in space. The detD factor, although strongly
      indicated previously, has not yet been derived deductively, as it is here. We
      take the opportunity to outline, starting from the reaction-diffusion equations,
      a sequence of mathematical steps leading to both geodesic and metric.

PMID- 25871169
TI  - Estimating the decomposition of predictive information in multivariate systems.
AB  - In the study of complex systems from observed multivariate time series, insight
      into the evolution of one system may be under investigation, which can be
      explained by the information storage of the system and the information transfer
      from other interacting systems. We present a framework for the model-free
      estimation of information storage and information transfer computed as the terms
      composing the predictive information about the target of a multivariate dynamical
      process. The approach tackles the curse of dimensionality employing a nonuniform
      embedding scheme that selects progressively, among the past components of the
      multivariate process, only those that contribute most, in terms of conditional
      mutual information, to the present target process. Moreover, it computes all
      information-theoretic quantities using a nearest-neighbor technique designed to
      compensate the bias due to the different dimensionality of individual entropy
      terms. The resulting estimators of prediction entropy, storage entropy, transfer
      entropy, and partial transfer entropy are tested on simulations of coupled linear
      stochastic and nonlinear deterministic dynamic processes, demonstrating the
      superiority of the proposed approach over the traditional estimators based on
      uniform embedding. The framework is then applied to multivariate physiologic time
      series, resulting in physiologically well-interpretable information
      decompositions of cardiovascular and cardiorespiratory interactions during head
      up tilt and of joint brain-heart dynamics during sleep. 

PMID- 25871170
TI  - Transitions from order to disorder in multiple dark and multiple dark-bright
      soliton atomic clouds.
AB  - We have performed a systematic study quantifying the variation of solitary wave
      behavior from that of an ordered cloud resembling a "crystalline" configuration
      to that of a disordered state that can be characterized as a soliton "gas." As
      our illustrative examples, we use both one-component, as well as two-component,
      one-dimensional atomic gases very close to zero temperature, where in the
      presence of repulsive interatomic interactions and of a parabolic trap, a cloud
      of dark (dark-bright) solitons can form in the one- (two-) component system. We
      corroborate our findings through three distinct types of approaches, namely a
      Gross-Pitaevskii type of partial differential equation, particle-based ordinary
      differential equations describing the soliton dynamical system, and Monte Carlo
      simulations for the particle system. We define an "empirical" order parameter to
      characterize the order of the soliton lattices and study how this changes as a
      function of the strength of the "thermally" (i.e., kinetically) induced
      perturbations. As may be anticipated by the one-dimensional nature of our system,
      the transition from order to disorder is gradual without, apparently, a genuine
      phase transition ensuing in the intermediate regime. 

PMID- 25871171
TI  - Signatures of chaos in the dynamics of quantum discord.
AB  - We identify signatures of chaos in the dynamics of discord in a multiqubit system
      collectively modelled as a quantum kicked top. The evolution of discord between
      any two qubits is quasiperiodic in regular regions, while in chaotic regions the
      quasiperiodicity is lost. As the initial wave function is varied from the regular
      regions to the chaotic sea, a contour plot of the time-averaged discord
      remarkably reproduces the structures of the classical stroboscopic map. We also
      find surprisingly opposite behavior of two-qubit discord versus entanglement of
      the two qubits as measured by the concurrence. Our results provide evidence of
      signatures of chaos in dynamically generated discord. 

PMID- 25871172
TI  - Analytical study of dynamics of matter-wave solitons in lossless nonlinear
      discrete bi-inductance transmission lines.
AB  - We consider a lossless one-dimensional nonlinear discrete bi-inductance
      electrical transmission line made of N identical unit cells. When lattice effects
      are considered, we use the reductive perturbation method in the semidiscrete
      limit to show that the dynamics of modulated waves can be modeled by the
      classical nonlinear Schrodinger (CNLS) equation, which describes the modulational
      instability and the propagation of bright and dark solitons on a continuous-wave
      background. Our theoretical analysis based on the CNLS equation predicts either
      two or four frequency regions with different behavior concerning the modulational
      instability of a plane wave. With the help of the analytical solutions of the
      CNLS equation, we investigate analytically the effects of the linear capacitance
      CS on the dynamics of matter-wave solitons in the network. Our results reveal
      that the linear parameter CS can be used to manipulate the motion of bright,
      dark, and kink soliton in the network.

PMID- 25871173
TI  - Paramagnetic colloidal ribbons in a precessing magnetic field.
AB  - We investigate the dynamics of a kink in a damped parametrically driven nonlinear
      Klein-Gordon equation. We show by using a method of averaging that, in the high
      frequency limit, the kink moves in an effective potential and is driven by an
      effective constant force. We demonstrate that the shape of the solitary wave can
      be controlled via the frequency and the eccentricity of the modulation. This is
      in accordance with the experimental results reported in a recent paper [Casic et
      al., Phys. Rev. Lett. 110, 168302 (2013)], where the dynamic self-assembly and
      propulsion of a ribbon formed from paramagnetic colloids in a time-dependent
      magnetic field has been studied.

PMID- 25871174
TI  - Self-organized patterns in successive bifurcations in planar semiconductor-gas
      discharge device.
AB  - The formation of dissipative structures is investigated in a planar semiconductor
      gas-discharge device at room temperature. The width of the discharge gap is about
      1 mm. The gap is filled with nitrogen at a pressure that corresponds to the
      discharge operation at the right branch of the Paschen curve. Wafers of semi
      insulating GaAs that exhibit linear transport in the whole range of voltage and
      current studied are used as semiconductor electrodes. In addition to the earlier
      investigated Andronov-Hopf bifurcation, a different mode of self-organization of
      the device is observed, where the transport of charge proceeds through an
      ensemble of pulsating current filaments. The corresponding critical current for
      the present bifurcation does not depend on the polarity of the bias voltage,
      while the spatiotemporal dynamics of a pattern differs substantially for a change
      in the polarity. Pulsating filaments can form a spatially ordered pattern when
      the GaAs electrode is under the positive potential. We also observe self
      organization modes, where pulsating filaments form an irregular spatiotemporal
      dynamics of a pattern. The data obtained are briefly discussed in the frame of
      corresponding theoretical results in the field. 

PMID- 25871175
TI  - Synchronization in an optomechanical cavity.
AB  - We study self-excited oscillations (SEO) in an on-fiber optomechanical cavity.
      Synchronization is observed when the optical power that is injected into the
      cavity is periodically modulated. A theoretical analysis based on the Fokker
      Planck equation evaluates the expected phase space distribution (PSD) of the self
      oscillating mechanical resonator. A tomography technique is employed for
      extracting PSD from the measured reflected optical power. Time-resolved state
      tomography measurements are performed to study phase diffusion and phase locking
      of the SEO. The detuning region inside which synchronization occurs is
      experimentally determined and the results are compared with the theoretical
      prediction. 

PMID- 25871176
TI  - Synchronization of tunable asymmetric square-wave pulses in delay-coupled
      optoelectronic oscillators.
AB  - We consider a model for two delay-coupled optoelectronic oscillators under
      positive delayed feedback as prototypical to study the conditions for
      synchronization of asymmetric square-wave oscillations, for which the duty cycle
      is not half of the period. We show that the scenario arising for positive
      feedback is much richer than with negative feedback. First, it allows for the
      coexistence of multiple in- and out-of-phase asymmetric periodic square waves for
      the same parameter values. Second, it is tunable: The period of all the square
      wave periodic pulses can be tuned with the ratio of the delays, and the duty
      cycle of the asymmetric square waves can be changed with the offset phase while
      the total period remains constant. Finally, in addition to the multiple in- and
      out-of-phase periodic square waves, low-frequency periodic asymmetric solutions
      oscillating in phase may coexist for the same values of the parameters. Our
      analytical results are in agreement with numerical simulations and bifurcation
      diagrams obtained by using continuation techniques. 

PMID- 25871177
TI  - Synchronization of networked chaotic oscillators under external periodic driving.
AB  - The dynamical responses of a complex system to external perturbations are of both
      fundamental interest and practical significance. Here, by the model of networked
      chaotic oscillators, we investigate how the synchronization behavior of a complex
      network is influenced by an externally added periodic driving. Interestingly, it
      is found that by a slight change of the properties of the external driving, e.g.,
      the frequency or phase lag between its intrinsic oscillation and external
      driving, the network synchronizability could be significantly modified. We
      demonstrate this phenomenon by different network models and, based on the method
      of master stability function, give an analysis on the underlying mechanisms. Our
      studies highlight the importance of external perturbations on the collective
      behaviors of complex networks, and also provide an alternate approach for
      controlling network synchronization. 

PMID- 25871178
TI  - Computer simulations of three-dimensional Turing patterns in the Lengyel-Epstein
      model.
AB  - We investigate numerically Turing patterns in the Lengyel-Epstein model in three
      dimensions. In a bulk homogeneous system under periodic boundary conditions, we
      obtain not only lamellar, cylindrical, and spherical structures but also several
      interconnected periodic structures including the Schwartz P-surface structure. In
      order to examine Turing patterns in the conditions accessible experimentally, we
      consider inhomogeneous systems where a parameter in the reaction-diffusion
      equations depends on the space coordinate with either Dirichlet or Neumann
      boundary conditions. In this situation, we find that a perforated-lamellar
      structure and an Fddd structure, both of which have a uniaxial symmetry, appear
      depending on the boundary conditions. 

PMID- 25871179
TI  - Nonautonomous discrete bright soliton solutions and interaction management for
      the Ablowitz-Ladik equation.
AB  - We present the nonautonomous discrete bright soliton solutions and their
      interactions in the discrete Ablowitz-Ladik (DAL) equation with variable
      coefficients, which possesses complicated wave propagation in time and differs
      from the usual bright soliton waves. The differential-difference similarity
      transformation allows us to relate the discrete bright soliton solutions of the
      inhomogeneous DAL equation to the solutions of the homogeneous DAL equation.
      Propagation and interaction behaviors of the nonautonomous discrete solitons are
      analyzed through the one- and two-soliton solutions. We study the discrete
      snaking behaviors, parabolic behaviors, and interaction behaviors of the discrete
      solitons. In addition, the interaction management with free functions and dynamic
      behaviors of these solutions is investigated analytically, which have certain
      applications in electrical and optical systems. 

PMID- 25871180
TI  - Nonparametric forecasting of low-dimensional dynamical systems.
AB  - This paper presents a nonparametric modeling approach for forecasting stochastic
      dynamical systems on low-dimensional manifolds. The key idea is to represent the
      discrete shift maps on a smooth basis which can be obtained by the diffusion maps
      algorithm. In the limit of large data, this approach converges to a Galerkin
      projection of the semigroup solution to the underlying dynamics on a basis
      adapted to the invariant measure. This approach allows one to quantify
      uncertainties (in fact, evolve the probability distribution) for nontrivial
      dynamical systems with equation-free modeling. We verify our approach on various
      examples, ranging from an inhomogeneous anisotropic stochastic differential
      equation on a torus, the chaotic Lorenz three-dimensional model, and the Nino-3.4
      data set which is used as a proxy of the El Nino Southern Oscillation. 

PMID- 25871181
TI  - Two-dimensional linear and nonlinear Talbot effect from rogue waves.
AB  - We introduce two-dimensional (2D) linear and nonlinear Talbot effects. They are
      produced by propagating periodic 2D diffraction patterns and can be visualized as
      3D stacks of Talbot carpets. The nonlinear Talbot effect originates from 2D rogue
      waves and forms in a bulk 3D nonlinear medium. The recurrences of an input rogue
      wave are observed at the Talbot length and at the half-Talbot length, with a pi
      phase shift; no other recurrences are observed. Differing from the nonlinear
      Talbot effect, the linear effect displays the usual fractional Talbot images as
      well. We also find that the smaller the period of incident rogue waves, the
      shorter the Talbot length. Increasing the beam intensity increases the Talbot
      length, but above a threshold this leads to a catastrophic self-focusing
      phenomenon which destroys the effect. We also find that the Talbot recurrence can
      be viewed as a self-Fourier transform of the initial periodic beam that is
      automatically performed during propagation. In particular, linear Talbot effect
      can be viewed as a fractional self-Fourier transform, whereas the nonlinear
      Talbot effect can be viewed as the regular self-Fourier transform. Numerical
      simulations demonstrate that the rogue-wave initial condition is sufficient but
      not necessary for the observation of the effect. It may also be observed from
      other periodic inputs, provided they are set on a finite background. The 2D
      effect may find utility in the production of 3D photonic crystals. 

PMID- 25871182
TI  - Subcriticality of the zigzag transition: A nonlinear bifurcation analysis.
AB  - When repelling particles are confined by a transverse potential in quasi-one
      dimensional geometry, the straight line equilibrium configuration becomes
      unstable at small confinement, in favor of a staggered row that may be
      inhomogeneous or homogeneous. This conformational phase transition is a pitchfork
      bifurcation called the zigzag transition. We study the zigzag transition in
      infinite and periodic finite systems with short-range interactions. We provide
      numerical evidence that in this case the bifurcation is subcritical since it
      exhibits phase coexistence and hysteretic behavior. The physical mechanism
      responsible for the change in the bifurcation character is the nonlinear coupling
      between the transverse soft mode at the transition and the longitudinal Goldstone
      mode linked to the translational or rotational invariance of the zigzag pattern.
      An asymptotic analysis, near the bifurcation threshold and assuming an infinite
      system, gives an explicit expression for the normal form of the bifurcation. We
      establish the subcriticality, and we describe with excellent precision the
      inhomogeneous zigzag patterns observed in the simulations. A direct test of the
      physical mechanism responsible for the bifurcation character evidences a
      quantitative agreement. 

PMID- 25871183
TI  - Chimera states in systems of nonlocal nonidentical phase-coupled oscillators.
AB  - Chimera states consisting of domains of coherently and incoherently oscillating
      nonlocally coupled phase oscillators in systems with spatial inhomogeneity are
      studied. The inhomogeneity is introduced through the dependence of the oscillator
      frequency on its location. Two types of spatial inhomogeneity, localized and
      spatially periodic, are considered and their effects on the existence and
      properties of multicluster and traveling chimera states are explored. The
      inhomogeneity is found to break up splay states, to pin the chimera states to
      specific locations, and to trap traveling chimeras. Many of these states can be
      studied by constructing an evolution equation for a complex order parameter.
      Solutions of this equation are in good agreement with the results of numerical
      simulations. 

PMID- 25871184
TI  - Energy-driven pattern formation in planar dipole-dipole systems in the presence
      of weak noise.
AB  - We study pattern formation in planar fluid systems driven by intermolecular
      cohesion (which manifests as a line tension) and dipole-dipole repulsion, which
      are observed in physical systems including ferrofluids in Hele-Shaw cells and
      Langmuir layers. When the dipolar repulsion is sufficiently strong, domains
      undergo forked branching reminiscent of viscous fingering. A known difficulty
      with these models is that the energy associated with dipole-dipole interactions
      is singular at small distances. Following previous work, we demonstrate how to
      ameliorate this singularity and show that in the macroscopic limit only the scale
      of the microscopic details relative to the macroscopic extent of a system is
      relevant and develop an expression for the system energy that depends only on a
      generalized line tension Lambda that in turn depends logarithmically on that
      scale. We conduct numerical studies that use energy minimization to find
      equilibrium states. Following the subcritical bifurcations from the circle, we
      find a few highly symmetric stable shapes, but nothing that resembles the
      observed diversity of experimental and dynamically simulated domains. The
      application of a weak random background to the energy landscape stabilizes a wide
      range of domain morphologies recovering the diversity observed experimentally.
      With this technique, we generate a large sample of qualitatively realistic shapes
      and use them to create an empirical model for extracting Lambda with high
      accuracy using only a shape's perimeter and morphology. 

PMID- 25871185
TI  - Nonsinusoidal current and current reversals in a gating ratchet.
AB  - In this work, the ratchet dynamics of Brownian particles driven by an external
      sinusoidal (harmonic) force is investigated. The gating ratchet effect is
      observed when another harmonic is used to modulate the spatially symmetric
      potential in which the particles move. For small amplitudes of the harmonics, it
      is shown that the current (average velocity) of particles exhibits a sinusoidal
      shape as a function of a precise combination of the phases of both harmonics. By
      increasing the amplitudes of the harmonics beyond the small-limit regime,
      departures from the sinusoidal behavior are observed and current reversals can
      also be induced. These current reversals persist even for the overdamped dynamics
      of the particles. 

PMID- 25871186
TI  - Microscopic instability in recurrent neural networks.
AB  - In a manner similar to the molecular chaos that underlies the stable
      thermodynamics of gases, a neuronal system may exhibit microscopic instability in
      individual neuronal dynamics while a macroscopic order of the entire population
      possibly remains stable. In this study, we analyze the microscopic stability of a
      network of neurons whose macroscopic activity obeys stable dynamics, expressing
      either monostable, bistable, or periodic state. We reveal that the network
      exhibits a variety of dynamical states for microscopic instability residing in a
      given stable macroscopic dynamics. The presence of a variety of dynamical states
      in such a simple random network implies more abundant microscopic fluctuations in
      real neural networks which consist of more complex and hierarchically structured
      interactions. 

PMID- 25871187
TI  - Internal noise and system size effects induce nondiffusive kink dynamics.
AB  - We investigate the effects of inherent fluctuations and system size in the
      dynamics of domain between uniform symmetric states. In the case of monotonous
      kinks, this dynamics is characterized by exhibiting nonsymmetric random walks,
      being attracted to the system borders. For nonmonotonous interface, the dynamics
      is replaced by a hopping dynamic. Based on bistable universal models, we
      characterize the origin of these unexpected dynamics through use of the
      stochastic kinematic laws for the interface position and the survival
      probability. Numerical simulations show a quite good agreement with the
      theoretical predictions. 

PMID- 25871188
TI  - Effective time-independent analysis for quantum kicked systems.
AB  - We present a mapping of potentially chaotic time-dependent quantum kicked systems
      to an equivalent approximate effective time-independent scenario, whereby the
      system is rendered integrable. The time evolution is factorized into an initial
      kick, followed by an evolution dictated by a time-independent Hamiltonian and a
      final kick. This method is applied to the kicked top model. The effective time
      independent Hamiltonian thus obtained does not suffer from spurious divergences
      encountered if the traditional Baker-Cambell-Hausdorff treatment is used. The
      quasienergy spectrum of the Floquet operator is found to be in excellent
      agreement with the energy levels of the effective Hamiltonian for a wide range of
      system parameters. The density of states for the effective system exhibits sharp
      peaklike features, pointing towards quantum criticality. The dynamics in the
      classical limit of the integrable effective Hamiltonian shows remarkable
      agreement with the nonintegrable map corresponding to the actual time-dependent
      system in the nonchaotic regime. This suggests that the effective Hamiltonian
      serves as a substitute for the actual system in the nonchaotic regime at both the
      quantum and classical level. 

PMID- 25871189
TI  - Origin of finite pulse trains: Homoclinic snaking in excitable media.
AB  - Many physical, chemical, and biological systems exhibit traveling waves as a
      result of either an oscillatory instability or excitability. In the latter case a
      large multiplicity of stable spatially localized wavetrains consisting of
      different numbers of traveling pulses may be present. The existence of these
      states is related here to the presence of homoclinic snaking in the vicinity of a
      subcritical, finite wavenumber Hopf bifurcation. The pulses are organized in a
      slanted snaking structure resulting from the presence of a heteroclinic cycle
      between small and large amplitude traveling waves. Connections of this type
      require a multivalued dispersion relation. This dispersion relation is computed
      numerically and used to interpret the profile of the pulse group. The different
      spatially localized pulse trains can be accessed by appropriately customized
      initial stimuli, thereby blurring the traditional distinction between oscillatory
      and excitable systems. The results reveal a new class of phenomena relevant to
      spatiotemporal dynamics of excitable media, particularly in chemical and
      biological systems with multiple activators and inhibitors. 

PMID- 25871190
TI  - Experimental investigation of the elastic enhancement factor in a transient
      region between regular and chaotic dynamics.
AB  - We present the results of an experimental study of the elastic enhancement factor
      W for a microwave rectangular cavity simulating a two-dimensional quantum
      billiard in a transient region between regular and chaotic dynamics. The cavity
      was coupled to a vector network analyzer via two microwave antennas. The
      departure of the system from an integrable one due to the presence of antennas
      acting as scatterers is characterized by the parameter of chaoticity kappa=2.8.
      The experimental results for the rectangular cavity are compared with those
      obtained for a microwave rough cavity simulating a chaotic quantum billiard. The
      experimental results were obtained for the frequency range nu=16-18.5 GHz and
      moderate absorption strength gamma=5.2-7.4. We show that the elastic enhancement
      factor for the rectangular cavity lies below the theoretical value W=3 predicted
      for integrable systems, and it is significantly higher than that obtained for the
      rough cavity. The results obtained for the microwave rough cavity are smaller
      than those obtained within the framework of random matrix theory, and they lie
      between them and those predicted within a recently introduced model of the two
      channel coupling [V. V. Sokolov and O. V. Zhirov, arXiv:1411.6211 [nucl-th]]. 

PMID- 25871191
TI  - Influence of the medium's dimensionality on defect-mediated turbulence.
AB  - Spatiotemporal chaos in oscillatory and excitable media is often characterized by
      the presence of phase singularities called defects. Understanding such defect
      mediated turbulence and its dependence on the dimensionality of a given system is
      an important challenge in nonlinear dynamics. This is especially true in the
      context of ventricular fibrillation in the heart, where the importance of the
      thickness of the ventricular wall is contentious. Here, we study defect-mediated
      turbulence arising in two different regimes in a conceptual model of excitable
      media and investigate how the statistical character of the turbulence changes if
      the thickness of the medium is changed from (quasi-) two- dimensional to three
      dimensional. We find that the thickness of the medium does not have a significant
      influence in, far from onset, fully developed turbulence while there is a clear
      transition if the system is close to a spiral instability. We provide clear
      evidence that the observed transition and change in the mechanism that drives the
      turbulent behavior is purely a consequence of the dimensionality of the medium.
      Using filament tracking, we further show that the statistical properties in the
      three-dimensional medium are different from those in turbulent regimes arising
      from filament instabilities like the negative line tension instability.
      Simulations also show that the presence of this unique three-dimensional
      turbulent dynamics is not model specific. 

PMID- 25871192
TI  - Instabilities and relaxation to equilibrium in long-range oscillator chains.
AB  - We study instabilities and relaxation to equilibrium in a long-range extension of
      the Fermi-Pasta-Ulam-Tsingou (FPU) oscillator chain by exciting initially the
      lowest Fourier mode. Localization in mode space is stronger for the long-range
      FPU model. This allows us to uncover the sporadic nature of instabilities, i.e.,
      by varying initially the excitation amplitude of the lowest mode, which is the
      control parameter, instabilities occur in narrow amplitude intervals. Only for
      sufficiently large values of the amplitude, the system enters a permanently
      unstable regime. These findings also clarify the long-standing problem of the
      relaxation to equilibrium in the short-range FPU model. Because of the weaker
      localization in mode space of this latter model, the transfer of energy is
      retarded and relaxation occurs on a much longer timescale. 

PMID- 25871193
TI  - Breather-to-soliton conversions described by the quintic equation of the
      nonlinear Schrodinger hierarchy.
AB  - We analyze the quintic integrable equation of the nonlinear Schrodinger hierarchy
      that includes fifth-order dispersion with matching higher-order nonlinear terms.
      We show that a breather solution of this equation can be converted into a
      nonpulsating soliton solution on a background. We calculate the locus of the
      eigenvalues on the complex plane which convert breathers into solitons. This
      transformation does not have an analog in the standard nonlinear Schrodinger
      equation. We also study the interaction between the new type of solitons, as well
      as between breathers and these solitons. 

PMID- 25871194
TI  - Delay-induced instability in a nutrient-phytoplankton system with flow.
AB  - In this paper, a nutrient-phytoplankton system described by a couple of advection
      diffusion-reaction equations with delay was studied analytically and numerically.
      The aim of this research was to provide an understanding of the impact of delay
      on instability. Significantly, delay cannot only induce instability, but can also
      promote the formation of spatial pattern via a Turing-like instability. In
      addition, the theoretical analysis indicates that the flow (advection term) may
      lead to instability when the delay term exists. By comparison, diffusion cannot
      result in Turing instability when flow does not exist. Results of numerical
      simulation were consistent with the analytical results. 

PMID- 25871195
TI  - Scroll waves pinned to moving heterogeneities.
AB  - Three-dimensional excitable systems can self-organize vortex patterns that rotate
      around one-dimensional phase singularities called filaments. In experiments with
      the Belousov-Zhabotinsky reaction and numerical simulations, we pin these scroll
      waves to translating inert cylinders and demonstrate the controlled repositioning
      of their rotation centers. If the pinning site extends only along a portion of
      the filament, the phase singularity is stretched out along the trajectory of the
      heterogeneity, which effectively writes the singularity into the system. Its
      trailing end point follows the heterogeneity with a lower velocity. This
      velocity, its dependence on the placement of the anchor, and the shape of the
      filament are explained by a curvature flow model. 

PMID- 25871196
TI  - Interface deformations due to counter-rotating vortices: Viscous versus elastic
      media.
AB  - Capillary forces determine the shape of a liquid interface. Although often not
      considered, elastic solids with a free surface are also subjected to surface
      forces and these become important for materials of low Young's modulus. Here we
      consider two equivalent problems where a capillary free surface deforms due to
      vortices: (i) in a steady viscous flow [solved by Jeong and Moffatt, J. Fluid
      Mech. 241, 1 (1992)], and (ii) in an elastic medium. The equations of linear
      incompressible elasticity and viscous flow are strictly identical, and the two
      dimensional problems that we consider are solved using complex variable methods.
      Despite the similarity, the kinematics of the free surface is very different for
      the viscous and elastic cases. We show for the present problem that these
      kinematics result in displacement and velocity fields of different topology.
      Unexpectedly, the resulting surface deflections are even of opposite sign.

PMID- 25871197
TI  - Fluid flow through packings of rotating obstacles.
AB  - We investigate through numerical simulation the nonstationary flow of a Newtonian
      fluid through a two-dimensional channel filled with an array of circular
      obstacles of distinct sizes. The disks may rotate around their respective
      centers, modeling a nonstationary, inhomogeneous porous medium. Obstacle sizes
      and positions are defined by the geometry of an Apollonian packing (AP). To allow
      for fluid flow, the radii of the disks are uniformly reduced by a factor
      0.6<=s<=0.8 for assemblies corresponding to the four first AP generations. The
      investigation is targeted to elucidate the main features of the rotating regime
      as compared to the fixed disk condition. It comprises the evaluation of the
      region of validity of Darcy's law as well as the study of the nonlinear hydraulic
      resistance as a function of the channel Reynolds number, the reduction factor s,
      and the AP generation. Depending on a combination of these factors, the
      resistance of rotating disks may be larger or smaller than that of the
      corresponding static case. We also analyze the flow redistribution in the
      interdisk channels as a result of the rotation pattern and characterize the
      angular velocity of the disks. Here, the striking feature is the emergence of a
      stable oscillatory behavior of the angular velocity for almost all disks that are
      inserted into the assemblies after the second generation. 

PMID- 25871198
TI  - Linear stability of a circular Couette flow under a radial thermoelectric body
      force.
AB  - The stability of the circular Couette flow of a dielectric fluid is analyzed by a
      linear perturbation theory. The fluid is confined between two concentric
      cylindrical electrodes of infinite length with only the inner one rotating. A
      temperature difference and an alternating electric tension are applied to the
      electrodes to produce a radial dielectrophoretic body force that can induce
      convection in the fluid. We examine the effects of superposition of this
      thermoelectric force with the centrifugal force including its thermal variation.
      The Earth's gravity is neglected to focus on the situations of a vanishing
      Grashof number such as microgravity conditions. Depending on the electric field
      strength and of the temperature difference, critical modes are either
      axisymmetric or nonaxisymmetric, occurring in either stationary or oscillatory
      states. An energetic analysis is performed to determine the dominant
      destabilizing mechanism. When the inner cylinder is hotter than the outer one,
      the circular Couette flow is destabilized by the centrifugal force for weak and
      moderate electric fields. The critical mode is steady axisymmetric, except for
      weak fields within a certain range of the Prandtl number and of the radius ratio
      of the cylinders, where the mode is oscillatory and axisymmetric. The frequency
      of this oscillatory mode is correlated with a Brunt-Vaisala frequency due to the
      stratification of both the density and the electric permittivity of the fluid.
      Under strong electric fields, the destabilization by the dielectrophoretic force
      is dominant, leading to oscillatory nonaxisymmetric critical modes with a
      frequency scaled by the frequency of the inner-cylinder rotation. When the outer
      cylinder is hotter than the inner one, the instability is again driven by the
      centrifugal force. The critical mode is axisymmetric and either steady under weak
      electric fields or oscillatory under strong electric fields. The frequency of the
      oscillatory mode is also correlated with the Brunt-Vaisala frequency. 

PMID- 25871199
TI  - Generalized lattice Boltzmann model for flow through tight porous media with
      Klinkenberg's effect.
AB  - Gas slippage occurs when the mean free path of the gas molecules is in the order
      of the characteristic pore size of a porous medium. This phenomenon leads to
      Klinkenberg's effect where the measured permeability of a gas (apparent
      permeability) is higher than that of the liquid (intrinsic permeability). A
      generalized lattice Boltzmann model is proposed for flow through porous media
      that includes Klinkenberg's effect, which is based on the model of Guo et al.
      [Phys. Rev. E 65, 046308 (2002)]. The second-order Beskok and Karniadakis-Civan's
      correlation [A. Beskok and G. Karniadakis, Microscale Thermophys. Eng. 3, 43
      (1999) and F. Civan, Transp. Porous Med. 82, 375 (2010)] is adopted to calculate
      the apparent permeability based on intrinsic permeability and the Knudsen number.
      Fluid flow between two parallel plates filled with porous media is simulated to
      validate the model. Simulations performed in a heterogeneous porous medium with
      components of different porosity and permeability indicate that Klinkenberg's
      effect plays a significant role on fluid flow in low-permeability porous media,
      and it is more pronounced as the Knudsen number increases. Fluid flow in a shale
      matrix with and without fractures is also studied, and it is found that the
      fractures greatly enhance the fluid flow and Klinkenberg's effect leads to higher
      global permeability of the shale matrix.

PMID- 25871200
TI  - Quantitative phase-field modeling for wetting phenomena.
AB  - A new phase-field model is developed for studying partial wetting. The
      introduction of a third phase representing a solid wall allows for the derivation
      of a new surface tension force that accounts for energy changes at the contact
      line. In contrast to other multi-phase-field formulations, the present model does
      not need the introduction of surface energies for the fluid-wall interactions.
      Instead, all wetting properties are included in a unique parameter known as the
      equilibrium contact angle thetaeq. The model requires the solution of a single
      elliptic phase-field equation, which, coupled to conservation laws for mass and
      linear momentum, admits the existence of steady and unsteady compact solutions
      (compactons). The representation of the wall by an additional phase field allows
      for the study of wetting phenomena on flat, rough, or patterned surfaces in a
      straightforward manner. The model contains only two free parameters, a measure of
      interface thickness W and beta, which is used in the definition of the mixture
      viscosity MU=MUlphil+MUvphiv+betaMUlphiw. The former controls the convergence
      towards the sharp interface limit and the latter the energy dissipation at the
      contact line. Simulations on rough surfaces show that by taking values for beta
      higher than 1, the model can reproduce, on average, the effects of pinning events
      of the contact line during its dynamic motion. The model is able to capture, in
      good agreement with experimental observations, many physical phenomena
      fundamental to wetting science, such as the wetting transition on micro
      structured surfaces and droplet dynamics on solid substrates.

PMID- 25871201
TI  - Effect of Peclet number on miscible rectilinear displacement in a Hele-Shaw cell.
AB  - The influence of fluid dispersion on the Saffman-Taylor instability in miscible
      fluids has been investigated in both the linear and the nonlinear regimes. The
      convective characteristic scales are used for the dimensionless formulation that
      incorporates the Peclet number (Pe) into the governing equations as a measure for
      the fluid dispersion. A linear stability analysis (LSA) is performed in a
      similarity transformation domain using the quasi-steady-state approximation. LSA
      results confirm that a flow with a large Pe has a higher growth rate than a flow
      with a small Pe. The critical Peclet number (Pec) for the onset of instability
      for all possible wave numbers and also a power-law relation of the onset time and
      most unstable wave number with Pe are observed. Unlike the radial source flow,
      Pec is found to vary with t0. A Fourier spectral method is used for direct
      numerical simulations (DNS) of the fully nonlinear system. The power-law
      dependence of the onset of instability ton on Pe is obtained from the DNS and
      found to be inversely proportional to Pe and it is in good agreement with that
      obtained from the LSA. The influence of the anisotropic dispersion is analyzed in
      both the linear and the nonlinear regimes. The results obtained confirm that for
      a weak transverse dispersion merging happens slowly and hence the small wave
      perturbations become unstable. We also observ that the onset of instability sets
      in early when the transverse dispersion is weak and varies with the anisotropic
      dispersion coefficient, epsilon, as ~?[epsilon], in compliance with the LSA. The
      combined effect of the Korteweg stress and Pe in the linear regime is pursued. It
      is observed that, depending on various flow parameters, a fluid system with a
      larger Pe exhibits a lower instantaneous growth rate than a system with a smaller
      Pe, which is contrary to the results when such stresses are absent.

PMID- 25871202
TI  - Hydrodynamic instability of elastic-plastic solid plates at the early stage of
      acceleration.
AB  - A model is presented for the linear Rayleigh-Taylor instability taking place at
      the early stage of acceleration of an elastic-plastic solid, when the shock wave
      is still running into the solid and is driven by a time varying pressure on the
      interface. When the the shock is formed sufficiently close to the interface, this
      stage is considered to follow a previous initial phase controlled by the
      Ritchmyer-Meshkov instability that settles new initial conditions. The model
      reproduces the behavior of the instability observed in former numerical
      simulation results and provides a relatively simpler physical picture than the
      currently existing one for this stage of the instability evolution. 

PMID- 25871203
TI  - Advanced dynamic-equilibrium model for a nanobubble and a micropancake on a
      hydrophobic or hydrophilic surface.
AB  - The dynamic-equilibrium model for stabilization of a nanobubble on a hydrophobic
      surface by Brenner and Lohse [M. P. Brenner and D. Lohse, Phys. Rev. Lett. 101,
      214505 (2008)] has been modified taking into account the van der Waals attractive
      force between gas molecules inside a nanobubble and solid surface. The present
      model is also applicable to a nanobubble on a hydrophilic surface. According to
      the model, the pressure inside a nanobubble is not spatially uniform and is
      relatively higher near the solid surface. As a result, there is gas outflux near
      a hydrophilic surface, while near a hydrophobic surface there is gas influx which
      has been already suggested. In the present model, the radius of curvature for a
      nanobubble depends on the distance from the solid surface because the pressure
      depends on it. The shape of the micropancake, which is a nearly-two-dimensional
      bubble, is reproduced by the present model due to the strong dependence of the
      radius of curvature on the distance from the solid surface. The effect of
      temperature on the stability of a nanobubble or micropancake is also discussed.

PMID- 25871204
TI  - How turbulence regulates biodiversity in systems with cyclic competition.
AB  - Cyclic, nonhierarchical interactions among biological species represent a general
      mechanism by which ecosystems are able to maintain high levels of biodiversity.
      However, species coexistence is often possible only in spatially extended systems
      with a limited range of dispersal, whereas in well-mixed environments models for
      cyclic competition often lead to a loss of biodiversity. Here we consider the
      dispersal of biological species in a fluid environment, where mixing is achieved
      by a combination of advection and diffusion. In particular, we perform a detailed
      numerical analysis of a model composed of turbulent advection, diffusive
      transport, and cyclic interactions among biological species in two spatial
      dimensions and discuss the circumstances under which biodiversity is maintained
      when external environmental conditions, such as resource supply, are uniform in
      space. Cyclic interactions are represented by a model with three competitors,
      resembling the children's game of rock-paper-scissors, whereas the flow field is
      obtained from a direct numerical simulation of two-dimensional turbulence with
      hyperviscosity. It is shown that the space-averaged dynamics undergoes
      bifurcations as the relative strengths of advection and diffusion compared to
      biological interactions are varied. 

PMID- 25871205
TI  - Upscale energy transfer and flow topology in free-surface turbulence.
AB  - Free-surface turbulence, albeit constrained onto a two-dimensional space,
      exhibits features that barely resemble predictions of simplified two-dimensional
      modeling. We demonstrate that, in a three-dimensional open channel flow, surface
      turbulence is characterized by upscale energy transfer, which controls the long
      term evolution of the larger scales. We are able to associate downscale and
      upscale energy transfer at the surface with the two-dimensional divergence of
      velocity. We finally demonstrate that surface compressibility confirms the
      strongly three-dimensional nature of surface turbulence. 

PMID- 25871206
TI  - Near-field acoustic streaming jet.
AB  - A numerical and experimental investigation of the acoustic streaming flow in the
      near field of a circular plane ultrasonic transducer in water is performed. The
      experimental domain is a parallelepipedic cavity delimited by absorbing walls to
      avoid acoustic reflection, with a top free surface. The flow velocities are
      measured by particle image velocimetry, leading to well-resolved velocity
      profiles. The theoretical model is based on a linear acoustic propagation model,
      which correctly reproduces the acoustic field mapped experimentally using a
      hydrophone, and an acoustic force term introduced in the Navier-Stokes equations
      under the plane-wave assumption. Despite the complexity of the acoustic field in
      the near field, in particular in the vicinity of the acoustic source, a good
      agreement between the experimental measurements and the numerical results for the
      velocity field is obtained, validating our numerical approach and justifying the
      planar wave assumption in conditions where it is a priori far from obvious. The
      flow structure is found to be correlated with the acoustic field shape. Indeed,
      the longitudinal profiles of the velocity present a wavering linked to the
      variations in acoustic intensity along the beam axis and transverse profiles
      exhibit a complex shape strongly influenced by the transverse variations of the
      acoustic intensity in the beam. Finally, the velocity in the jet is found to
      increase as the square root of the acoustic force times the distance from the
      origin of the jet over a major part of the cavity, after a strong short initial
      increase, where the velocity scales with the square of the distance from the
      upstream wall. 

PMID- 25871207
TI  - Hydrodynamic analysis of flagellated bacteria swimming near one and between two
      no-slip plane boundaries.
AB  - The motility of swimming bacteria near solid surfaces has implications in a wide
      range of scenarios, including water treatment facilities, microfluidics, and
      biomedical implants. Using the boundary element method to numerically solve the
      equations of low Reynolds number fluid flow, we investigate the dynamics of a
      model swimmer propelled by rotating a single helical flagellum. Building on
      previous simulation results for swimmers near a single plane boundary, we
      introduce a second, parallel boundary and show that the bacterial trajectories
      change as the two plates are brought closer together. Analysis of this dynamical
      system shows that the configuration in the center of the channel and parallel to
      the walls is an unstable equilibrium state for large plate separations, but it
      becomes the only stable position for swimmers when the plate separation is
      reduced to three to four times the cell width. Our model also predicts that
      transient trajectories, i.e., those not at steady states, can exhibit curvature
      in the opposite sense to that expected from the well-known explanation for
      circular bacterial paths near a single wall. 

PMID- 25871208
TI  - Two-dimensional homogeneous isotropic fluid turbulence with polymer additives.
AB  - We carry out an extensive and high-resolution direct numerical simulation of
      homogeneous, isotropic turbulence in two-dimensional fluid films with air-drag
      induced friction and with polymer additives. Our study reveals that the polymers
      (a) reduce the total fluid energy, enstrophy, and palinstrophy; (b) modify the
      fluid energy spectrum in both inverse- and forward-cascade regimes; (c) reduce
      small-scale intermittency; (d) suppress regions of high vorticity and strain
      rate; and (e) stretch in strain-dominated regions. We compare our results with
      earlier experimental studies and propose new experiments. 

PMID- 25871209
TI  - Metamorphosis of helical magnetorotational instability in the presence of axial
      electric current.
AB  - This paper presents numerical linear stability analysis of a cylindrical Taylor
      Couette flow of liquid metal carrying axial electric current in a generally
      helical external magnetic field. Axially symmetric disturbances are considered in
      the inductionless approximation corresponding to zero magnetic Prandtl number.
      Axial symmetry allows us to reveal an entirely new electromagnetic instability.
      First, we show that the electric current passing through the liquid can extend
      the range of helical magnetorotational instability (HMRI) indefinitely by
      transforming it into a purely electromagnetic instability. Two different
      electromagnetic instability mechanisms are identified. The first is an internal
      pinch-type instability, which is due to the interaction of the electric current
      with its own magnetic field. Axisymmetric mode of this instability requires a
      free-space component of the azimuthal magnetic field. When the azimuthal
      component of the magnetic field is purely rotational and the axial component is
      nonzero, a new kind of electromagnetic instability emerges. The latter, driven by
      the interaction of electric current with a weak collinear magnetic field in a
      quiescent fluid, gives rise to a steady meridional circulation coupled with
      azimuthal rotation. 

PMID- 25871210
TI  - Absorption of waves by large-scale winds in stratified turbulence.
AB  - The atmosphere is a nonlinear stratified fluid in which internal gravity waves
      are present. These waves interact with the flow, resulting in wave turbulence
      that displays important differences with the turbulence observed in isotropic and
      homogeneous flows. We study numerically the role of these waves and their
      interaction with the large-scale flow, consisting of vertically sheared
      horizontal winds. We calculate their space- and time-resolved energy spectrum (a
      four-dimensional spectrum) and show that most of the energy is concentrated along
      a dispersion relation that is Doppler shifted by the horizontal winds. We also
      observe that when uniform winds are let to develop in each horizontal layer of
      the flow, waves whose phase velocity is equal to the horizontal wind speed have
      negligible energy. This indicates a nonlocal transfer of their energy to the mean
      flow. Both phenomena, the Doppler shift and the absorption of waves traveling
      with the wind speed, are not accounted for in current theories of stratified wave
      turbulence. 

PMID- 25871211
TI  - Anisotropic particle in viscous shear flow: Navier slip, reciprocal symmetry, and
      Jeffery orbit.
AB  - The hydrodynamic reciprocal theorem for Stokes flows is generalized to
      incorporate the Navier slip boundary condition, which can be derived from
      Onsager's variational principle of least energy dissipation. The hydrodynamic
      reciprocal relations and the Jeffery orbit, both of which arise from the motion
      of a slippery anisotropic particle in a simple viscous shear flow, are
      investigated theoretically and numerically using the fluid particle dynamics
      method [Phys. Rev. Lett. 85, 1338 (2000)]. For a slippery elliptical particle in
      a linear shear flow, the hydrodynamic reciprocal relations between the rotational
      torque and the shear stress are studied and related to the Jeffery orbit, showing
      that the boundary slip can effectively enhance the anisotropy of the particle.
      Physically, by replacing the no-slip boundary condition with the Navier slip
      condition at the particle surface, the cross coupling between the rotational
      torque and the shear stress is enhanced, as manifested through a dimensionless
      parameter in both of the hydrodynamic reciprocal relations and the Jeffery orbit.
      In addition, simulations for a circular particle patterned with portions of no
      slip and Navier slip are carried out, showing that the particle possesses an
      effective anisotropy and follows the Jeffery orbit as well. This effective
      anisotropy can be tuned by changing the ratio of no-slip portion to slip potion.
      The connection of the present work to nematic liquid crystals' constitutive
      relations is discussed.

PMID- 25871212
TI  - Log-stable law of energy dissipation as a framework of turbulence intermittency.
AB  - To describe the small-scale intermittency of turbulence, a self-similarity is
      assumed for the probability density function of a logarithm of the rate of energy
      dissipation smoothed over a length scale among those in the inertial range. The
      result is an extension of Kolmogorov's classical theory [A. N. Kolmogorov, Dokl.
      Akad. Nauk SSSR 30, 301 (1941)], i.e., a one-parameter framework where the
      logarithm obeys some stable distribution. Scaling laws are obtained for the
      dissipation rate and for the two-point velocity difference. They are consistent
      with theoretical constraints and with the observed scaling laws. Also discussed
      is the physics that determines the value of the parameter.

PMID- 25871213
TI  - Statistical conservation law in two- and three-dimensional turbulent flows.
AB  - Particles in turbulence live complicated lives. It is nonetheless sometimes
      possible to find order in this complexity. It was proposed in Falkovich et al.
      [Phys. Rev. Lett. 110, 214502 (2013)] that pairs of Lagrangian tracers at small
      scales, in an incompressible isotropic turbulent flow, have a statistical
      conservation law. More specifically, in a d-dimensional flow the distance R(t)
      between two neutrally buoyant particles, raised to the power -d and averaged over
      velocity realizations, remains at all times equal to the initial, fixed,
      separation raised to the same power. In this work we present evidence from direct
      numerical simulations of two- and three-dimensional turbulence for this
      conservation. In both cases the conservation is lost when particles exit the
      linear flow regime. In two dimensions we show that, as an extension of the
      conservation law, an Evans-Cohen-Morriss or Gallavotti-Cohen type fluctuation
      relation exists. We also analyze data from a 3D laboratory experiment [Liberzon
      et al., Physica D 241, 208 (2012)], finding that although it probes small scales
      they are not in the smooth regime. Thus instead of <R-3>, we look for a similar,
      power-law-in-separation conservation law. We show that the existence of an
      initially slowly varying function of this form can be predicted but that it does
      not turn into a conservation law. We suggest that the conservation of <R-d>,
      demonstrated here, can be used as a check of isotropy, incompressibility, and
      flow dimensionality in numerical and laboratory experiments that focus on small
      scales.

PMID- 25871214
TI  - Flow-induced separation in wall turbulence.
AB  - One of the defining characteristics of turbulence is its ability to promote
      mixing. We present here a case where the opposite happens-simulation results
      indicate that particles can separate near the wall of a turbulent channel flow,
      when they have sufficiently different Schmidt numbers without use of any other
      means. The physical mechanism of the separation is understood when the interplay
      between convection and diffusion, as expressed by their characteristic time
      scales, is considered, leading to the determination of the necessary conditions
      for a successful separation between particles. Practical applications of these
      results can be found when very small particles need to be separated or removed
      from a fluid. 

PMID- 25871215
TI  - Flows and mixing in channels with misaligned superhydrophobic walls.
AB  - Aligned superhydrophobic surfaces with the same texture orientation reduce drag
      in the channel and generate secondary flows transverse to the direction of the
      applied pressure gradient. Here we show that a transverse shear can be easily
      generated by using superhydrophobic channels with misaligned textured surfaces.
      We propose a general theoretical approach to quantify this transverse flow by
      introducing the concept of an effective shear tensor. To illustrate its use, we
      present approximate theoretical solutions and Dissipative Particle Dynamics
      simulations for striped superhydrophobic channels. Our results demonstrate that
      the transverse shear leads to complex flow patterns, which provide a new
      mechanism of a passive vertical mixing at the scale of a texture period.
      Depending on the value of Reynolds number two different scenarios occur. At
      relatively low Reynolds number the flow represents a transverse shear
      superimposed with two corotating vortices. For larger Reynolds number these
      vortices become isolated, by suppressing fluid transport in the transverse
      direction. 

PMID- 25871216
TI  - Scaling regimes of thermocapillarity-driven dynamics of confined long bubbles:
      Effects of disjoining pressure.
AB  - During thermocapillary transport of a confined long bubble, we unveil the
      existence of a contrary-to-the-conventional disjoining-pressure-dominant scaling
      regime characterizing the dynamics of the thin liquid film engulfed between the
      bubble interface and the channel surface. Such a regime is realized for the
      limitingly small magnitude of the Marangoni stress (surface tension gradient)
      when the separating liquid region reaches an ultrathin dimension. Over this
      regime, we witness a severe breakdown of the seemingly intuitive scaling
      arguments based on the balance of viscous and capillary forces. Starting from
      competent balance criteria, we uncover the characteristic length scales involved,
      leading towards obtaining the new consistent scaling laws of the disjoining
      pressure-dominant regime, in a simple closed form analytical fashion. Our scaling
      estimations are substantiated by full-scale numerical simulations of the
      pertinent thin-film equations. These new scaling laws appear to be convenient for
      implementing as a fundamental design basis for multiphase microfluidic systems. 

PMID- 25871217
TI  - Fluid infiltration pressure for hydrophobic nanochannels.
AB  - We investigate water infiltration pressure for hydrophobic nanochannels through
      molecular dynamics simulations. It is found that the entrance energy barrier
      significantly raises the infiltration pressure, which makes the classic Young
      Laplace equation invalid for nanochannels. As the channel surface is tuned from
      superhydrophobic to hydrophobic, the infiltration pressure is greatly reduced
      mainly due to the decrease of the capillary pressure (Young-Laplace equation)
      caused by the contact angle change, while the contribution of the entrance energy
      barrier to the infiltration pressure, which is termed entrance barrier pressure,
      increases from 25% to 60%. 

PMID- 25871218
TI  - Using higher ionization states to increase Coulomb coupling in an ultracold
      neutral plasma.
AB  - We report measurements and simulations of the time-evolving rms velocity
      distribution in an ultracold neutral plasma. A strongly coupled ultracold neutral
      Ca+ plasma is generated by photoionizing laser-cooled atoms close to threshold. A
      fraction of these ions is then promoted to the second ionization state to form a
      mixed Ca+-Ca2+ plasma. By varying the time delay between the first and the second
      ionization events, a minimum in ion heating is achieved. We show that the Coulomb
      strong-coupling parameter Gamma increases by a factor of 1.4 to a maximum value
      of 3.6. A pure Ca2+ plasma would have Gamma=6.8, moving these strongly coupled
      systems closer to the regime of liquid-like correlations.

PMID- 25871219
TI  - Relativistic breather-type solitary waves with linear polarization in cold
      plasmas.
AB  - Linearly polarized solitary waves, arising from the interaction of an intense
      laser pulse with a plasma, are investigated. Localized structures, in the form of
      exact numerical nonlinear solutions of the one-dimensional Maxwell-fluid model
      for a cold plasma with fixed ions, are presented. Unlike stationary circularly
      polarized solitary waves, the linear polarization gives rise to a breather-type
      behavior and a periodic exchange of electromagnetic energy and electron kinetic
      energy at twice the frequency of the wave. A numerical method based on a finite
      differences scheme allows us to compute a branch of solutions within the
      frequency range Omegamin<Omega<omegape, where omegape and Omegamin are the
      electron plasma frequency and the frequency value for which the plasma density
      vanishes locally, respectively. A detailed description of the spatiotemporal
      structure of the waves and their main properties as a function of Omega is
      presented. Small-amplitude oscillations appearing in the tail of the solitary
      waves, a consequence of the linear polarization and harmonic excitation, are
      explained with the aid of the Akhiezer-Polovin system. Direct numerical
      simulations of the Maxwell-fluid model show that these solitary waves propagate
      without change for a long time.

PMID- 25871220
TI  - Giant cross-magnetic-field steps due to binary collisions between pair particles.
AB  - Giant cross-magnetic-field steps can occur as a result of positron-electron
      collisions. Within a constant magnetic field (e.g., 1 T), a collision between a
      positron and an electron can result in a correlated drift across the magnetic
      field for a continuous range of impact parameters. Within this range, drift
      distances orders of magnitude larger than that associated with like-charge
      collisions were observed by computer simulation. Outside of this range, the
      collisional behavior is similar to that for collisions between particles with the
      same charge. A theoretical analysis of the phenomenon using center-of-mass and
      relative coordinates provides insights regarding the occurrence of giant cross
      magnetic-field steps. 

PMID- 25871221
TI  - Unified description of linear screening in dense plasmas.
AB  - Electron screening of ions is among the most fundamental properties of plasmas,
      determining the effective ionic interactions that impact all properties of a
      plasma. With the development of new experimental facilities that probe high
      energy-density physics regimes ranging from warm dense matter to hot dense
      matter, a unified framework for describing dense plasma screening has become
      essential. Such a unified framework is presented here based on finite-temperature
      orbital-free density functional theory, including gradient corrections and
      exchange-correlation effects. We find a new analytic pair potential for the ion
      ion interaction that incorporates moderate electronic coupling, quantum
      degeneracy, gradient corrections to the free energy, and finite temperatures.
      This potential can be used in large-scale "classical" molecular dynamics
      simulations, as well as in simpler theoretical models (e.g., integral equations
      and Monte Carlo), with no additional computational complexity. The new potential
      theoretically connects limits of Debye-Huckel-Yukawa, Lindhard, Thomas-Fermi, and
      Bohmian quantum hydrodynamics descriptions. Based on this new potential, we
      predict ionic static structure factors that can be validated using x-ray Thomson
      scattering data. 

PMID- 25871222
TI  - Nonlinear ion-acoustic cnoidal waves in a dense relativistic degenerate
      magnetoplasma.
AB  - The complex pattern and propagation characteristics of nonlinear periodic ion
      acoustic waves, namely, ion-acoustic cnoidal waves, in a dense relativistic
      degenerate magnetoplasma consisting of relativistic degenerate electrons and
      nondegenerate cold ions are investigated. By means of the reductive perturbation
      method and appropriate boundary conditions for nonlinear periodic waves, a
      nonlinear modified Korteweg-de Vries (KdV) equation is derived and its cnoidal
      wave is analyzed. The various solutions of nonlinear ion-acoustic cnoidal and
      solitary waves are presented numerically with the Sagdeev potential approach. The
      analytical solution and numerical simulation of nonlinear ion-acoustic cnoidal
      waves of the nonlinear modified KdV equation are studied. Clearly, it is found
      that the features (amplitude and width) of nonlinear ion-acoustic cnoidal waves
      are proportional to plasma number density, ion cyclotron frequency, and direction
      cosines. The numerical results are applied to high density astrophysical
      situations, such as in superdense white dwarfs. This research will be helpful in
      understanding the properties of compact astrophysical objects containing cold
      ions with relativistic degenerate electrons. 

PMID- 25871223
TI  - Electric microfields in dense carbon-hydrogen plasmas.
AB  - Classical molecular dynamics is used to investigate stationary and time-dependent
      properties of microfields in hot, solid density, electron-ion plasmas. Even at
      the high temperatures considered here, such simulations require quantum
      statistical potentials (QSPs) to mimic the essential effects of diffraction and
      exchange symmetry for electrons. Fortunately, key results relevant to microfield
      distributions are found to be insensitive to different, plausible QSP choices.
      Atomic processes in plasmas will depend on the time average of the microfields.
      It is not clear, a priori, what the time duration of this average should be. The
      question of how best to extract the quasistatic (low-frequency) microfield from a
      classical molecular dynamics simulation is explored in some detail, and the time
      averaging approach we adopt involves both plasma and atomic time scale
      constraints. One of the major findings described in the paper is that for a large
      time interval, the time-averaged microfield does not significantly change. Our
      discussion of this suite of large simulations for plasma mixtures focuses on
      understanding various features and trends revealed by data for C-H plasmas having
      carbon fractions ranging from 0.01 to 1, and different temperatures well above
      TFermi.

PMID- 25871224
TI  - Fast-electron refluxing effects on anisotropic hard-x-ray emission from intense
      laser-plasma interactions.
AB  - Fast-electron generation and dynamics, including electron refluxing, is at the
      core of understanding high-intensity laser-plasma interactions. This field is
      itself of strong relevance to fast ignition fusion and the development of new
      short-pulse, intense, x-ray, gamma-ray, and particle sources. In this paper, we
      describe experiments that explicitly link fast-electron refluxing and anisotropy
      in hard-x-ray emission. We find the anisotropy in x-ray emission to be strongly
      correlated to the suppression of refluxing. In contrast to some previous work,
      the peak of emission is directly along the rear normal to the target rather than
      along either the incident laser direction or the specular reflection direction. 

PMID- 25871225
TI  - Fermionic path-integral Monte Carlo results for the uniform electron gas at
      finite temperature.
AB  - The uniform electron gas (UEG) at finite temperature has recently attracted
      substantial interest due to the experimental progress in the field of warm dense
      matter. To explain the experimental data, accurate theoretical models for high
      density plasmas are needed that depend crucially on the quality of the
      thermodynamic properties of the quantum degenerate nonideal electrons and of the
      treatment of their interaction with the positive background. Recent fixed-node
      path-integral Monte Carlo (RPIMC) data are believed to be the most accurate for
      the UEG at finite temperature, but they become questionable at high degeneracy
      when the Brueckner parameter rs=a/aB--the ratio of the mean interparticle
      distance to the Bohr radius--approaches 1. The validity range of these
      simulations and their predictive capabilities for the UEG are presently unknown.
      This is due to the unknown quality of the used fixed nodes and of the finite-size
      scaling from N=33 simulated particles (per spin projection) to the macroscopic
      limit. To analyze these questions, we present alternative direct fermionic path
      integral Monte Carlo (DPIMC) simulations that are independent from RPIMC. Our
      simulations take into account quantum effects not only in the electron system but
      also in their interaction with the uniform positive background. Also, we use
      substantially larger particle numbers (up to three times more) and perform an
      extrapolation to the macroscopic limit. We observe very good agreement with
      RPIMC, for the polarized electron gas, up to moderate densities around rs=4, and
      larger deviations for the unpolarized case, for low temperatures. For higher
      densities (high electron degeneracy), rs?1.5, both RPIMC and DPIMC are
      problematic due to the increased fermion sign problem.

PMID- 25871226
TI  - Revealing an intermediate region between the collisional radiofrequency plasma
      bulk and its sheath.
AB  - Experimental evidence of the existence of an intermediate region between a
      capacitively coupled plasma and the collisional space-charge region at its
      borders is presented. This proof is generated by monitoring-in an airplane
      carrying out parabolic flights-the trajectory of plasma-confined microparticles.
      Based on only primary data and without the need for a sophisticated model, our
      analysis concludes a sharply marked transition from the sheath region into
      another region with a significantly lower-yet nonzero-space-charge density, i.e.,
      a region which is often called the presheath. 

PMID- 25871227
TI  - Fluid approach to evaluate sound velocity in Yukawa systems and complex plasmas.
AB  - The conventional fluid description of multicomponent plasma, supplemented by an
      appropriate equation of state for the macroparticle component, is used to
      evaluate the longitudinal sound velocity of Yukawa fluids. The obtained results
      are in very good agreement with those obtained earlier employing the
      quasilocalized charge approximation and molecular dynamics simulations in a
      rather broad parameter regime. Thus, a simple yet accurate tool to estimate the
      sound velocity across coupling regimes is proposed, which can be particularly
      helpful in estimating the dust-acoustic velocity in strongly coupled dusty
      (complex) plasmas. It is shown that, within the present approach, the sound
      velocity is completely determined by particle-particle correlations and the
      neutralizing medium (plasma), apart from providing screening of the Coulomb
      interaction, has no other effect on the sound propagation. The ratio of the
      actual sound velocity to its "ideal gas" (weak coupling) scale only weakly
      depends on the coupling strength in the fluid regime but exhibits a pronounced
      decrease with the increase of the screening strength. The limitations of the
      present approach in applications to real complex plasmas are briefly discussed. 

PMID- 25871228
TI  - Separated spin-up and spin-down quantum hydrodynamics of degenerated electrons:
      Spin-electron acoustic wave appearance.
AB  - The quantum hydrodynamic (QHD) model of charged spin-1/2 particles contains
      physical quantities defined for all particles of a species including particles
      with spin-up and with spin-down. Different populations of states with different
      spin directions are included in the spin density (the magnetization). In this
      paper I derive a QHD model, which separately describes spin-up electrons and spin
      down electrons. Hence electrons with different projections of spins on the
      preferable direction are considered as two different species of particles. It is
      shown that the numbers of particles with different spin directions do not
      conserve. Hence the continuity equations contain sources of particles. These
      sources are caused by the interactions of the spins with the magnetic field.
      Terms of similar nature arise in the Euler equation. The z projection of the spin
      density is no longer an independent variable. It is proportional to the
      difference between the concentrations of the electrons with spin-up and the
      electrons with spin-down. The propagation of waves in the magnetized plasmas of
      degenerate electrons is considered. Two regimes for the ion dynamics, the
      motionless ions and the motion of the degenerate ions as the single species with
      no account of the spin dynamics, are considered. It is shown that this form of
      the QHD equations gives all solutions obtained from the traditional form of QHD
      equations with no distinction of spin-up and spin-down states. But it also
      reveals a soundlike solution called the spin-electron acoustic wave. Coincidence
      of most solutions is expected since this derivation was started with the same
      basic equation: the Pauli equation. Solutions arise due to the different Fermi
      pressures for the spin-up electrons and the spin-down electrons in the magnetic
      field. The results are applied to degenerate electron gas of paramagnetic and
      ferromagnetic metals in the external magnetic field. The dispersion of the spin
      electron acoustic waves in the partially spin-polarized degenerate neutron matter
      are also considered. 

PMID- 25871229
TI  - Ab initio approach to model x-ray diffraction in warm dense matter.
AB  - It is demonstrated how the static electron-electron structure factor in warm
      dense matter can be obtained from density functional theory in combination with
      quantum Monte Carlo data. In contrast to theories assuming well-separated bound
      and free states, this ab initio approach yields also valid results for systems
      close to the Mott transition (pressure ionization), where bound states are
      strongly modified and merge with the continuum. The approach is applied to x-ray
      Thomson scattering and compared to predictions of the Chihara formula whereby we
      use the ion-ion and electron-ion structure from the same simulations. The results
      show significant deviations of the screening cloud from the often applied Debye
      like form. 

PMID- 25871230
TI  - Drift wave stabilized by an additional streaming ion or plasma population.
AB  - It is shown that the universally unstable kinetic drift wave in an electron-ion
      plasma can very effectively be suppressed by adding an extra flowing ion (or
      plasma) population. The effect of the flow of the added ions is essential, their
      response is of the type (vph-vf0)exp[-(vph-vf0)2], where vf0 is the flow speed
      and vph is the phase speed parallel to the magnetic field vector. The damping is
      strong and it is mainly due to this ion exponential term, and this remains so for
      vf0<vph.

PMID- 25871231
TI  - Average-atom model combined with the hypernetted chain approximation applied to
      warm dense matter.
AB  - We have combined the average-atom model with the hypernetted chain approximation
      (AAHNC) to describe the electronic and ionic structure in the warm dense matter
      regime. On the basis of the electronic and ionic structures, the x-ray Thomson
      scattering (XRTS) spectrum is calculated using the random-phase approximation.
      While the electronic structure is described within the average-atom model, the
      effects of other ions on the electronic structure are considered using an
      integral equation method of the theory of liquids, namely the hypernetted chain
      approximation. The ion-ion pair potential is calculated using the modified Gordon
      Kim model based on the electronic density distribution. Finally, the electronic
      and ionic structures are determined self-consistently. The XRTS spectrum is
      calculated according to the Chihara formula, where the scattering contributions
      are divided into three components: elastic, bound-free, and free-free. Comparison
      of the present AAHNC results with other theoretical models and experimental data
      shows very good agreement. Thus the AAHNC model can give a reasonable description
      of the electronic and ionic structure in warm dense matter. 

PMID- 25871232
TI  - Higher-order-effects management of soliton interactions in the Hirota equation.
AB  - The study of soliton interactions is of significance for improving pulse
      qualities in nonlinear optics. In this paper, interaction between two solitons,
      which is governed by the Hirota equation, is considered. Via use of the Hirota
      method, an analytic soliton solution is obtained. Then a two-period vibration
      phenomenon is observed. Moreover, turning points of the coefficients of higher
      order terms, which are related with sudden delaying or leading, are found and
      analyzed. With different coefficient constraints, soliton interactions are
      discussed by different frequency separation with the split-step Fourier method,
      and characteristics of soliton interactions are exhibited. Through turning
      points, we get a pair of solitons which tend to be bound solitons but not
      exactly. Furthermore, we control a pair of solitons to emit at different emission
      angles. The stability of the two-period vibration is analyzed. Results in this
      paper may be helpful for the applications of optical self-routing, waveguiding,
      and faster switching. 

PMID- 25871233
TI  - Dark and antidark soliton interactions in the nonlocal nonlinear Schrodinger
      equation with the self-induced parity-time-symmetric potential.
AB  - Via the Nth Darboux transformation, a chain of nonsingular localized-wave
      solutions is derived for a nonlocal nonlinear Schrodinger equation with the self
      induced parity-time (PT) -symmetric potential. It is found that the Nth iterated
      solution in general exhibits a variety of elastic interactions among 2N solitons
      on a continuous-wave background and each interacting soliton could be the dark or
      antidark type. The interactions with an arbitrary odd number of solitons can also
      be obtained under different degenerate conditions. With N=1 and 2, the two
      soliton and four-soliton interactions and their various degenerate cases are
      discussed in the asymptotic analysis. Numerical simulations are performed to
      support the analytical results, and the stability analysis indicates that the PT
      symmetry breaking can also destroy the stability of the soliton interactions. 

PMID- 25871234
TI  - Geometric origin of negative Casimir entropies: A scattering-channel analysis.
AB  - Negative values of the Casimir entropy occur quite frequently at low temperatures
      in arrangements of metallic objects. The physical reason lies either in the
      dissipative nature of the metals as is the case for the plane-plane geometry or
      in the geometric form of the objects involved. Examples for the latter are the
      sphere-plane and the sphere-sphere geometry, where negative Casimir entropies can
      occur already for perfect metal objects. After appropriately scaling out the size
      of the objects, negative Casimir entropies of geometric origin are particularly
      pronounced in the limit of large distances between the objects. We analyze this
      limit in terms of the different scattering channels and demonstrate how the
      negativity of the Casimir entropy is related to the polarization mixing arising
      in the scattering process. If all involved objects have a finite zero-frequency
      conductivity, the channels involving transverse electric modes are suppressed and
      the Casimir entropy within the large-distance limit is found to be positive. 

PMID- 25871235
TI  - Circular polarization memory in polydisperse scattering media.
AB  - We investigate the survival of circularly polarized light in random scattering
      media. The surprising persistence of this form of polarization has a known
      dependence on the size and refractive index of scattering particles, however a
      general description regarding polydisperse media is lacking. Through analysis of
      Mie theory, we present a means of calculating the magnitude of circular
      polarization memory in complex media, with total generality in the distribution
      of particle sizes and refractive indices. Quantification of this memory effect
      enables an alternate pathway toward recovering particle size distribution, based
      on measurements of diffusing circularly polarized light. 

PMID- 25871236
TI  - Effects of scars on icosahedral crystalline shell stability under external
      pressure.
AB  - We study how the stability of spherical crystalline shells under external
      pressure is influenced by the defect structure. In particular, we compare
      stability for shells with a minimal set of topologically required defects to
      shells with extended defect arrays (grain boundary "scars" with nonvanishing net
      disclination charge). We perform both Monte Carlo and conjugate gradient
      simulations to compare how shells with and without scars deform quasistatically
      under external hydrostatic pressure. We find that the critical pressure at which
      shells collapse is lowered for scarred configurations that break icosahedral
      symmetry and raised for scars that preserve icosahedral symmetry. The particular
      shapes which arise from breaking of an initial icosahedrally symmetric shell
      depend on the Foppl-von Karman number. 

PMID- 25871237
TI  - Time-frequency dynamics of superluminal pulse transition to the subluminal
      regime.
AB  - Spectral reshaping and nonuniform phase delay associated with an electromagnetic
      pulse propagating in a temporally dispersive medium may lead to interesting
      observations in which the group velocity becomes superluminal or even negative.
      In such cases, the finite bandwidth of the superluminal region implies the
      inevitable existence of a cutoff distance beyond which a superluminal pulse
      becomes subluminal. In this paper, we derive a closed-form analytic expression to
      estimate this cutoff distance in abnormal dispersive media with gain. Moreover,
      the method of steepest descent is used to track the time-frequency dynamics
      associated with the evolution of the center of mass of a superluminal pulse to
      the subluminal regime. This evolution takes place at longer propagation depths as
      a result of the subluminal components affecting the behavior of the pulse.
      Finally, the analysis presents the fundamental limitations of superluminal
      propagation in light of factors such as the medium depth, pulse width, and the
      medium dispersion strength. 

PMID- 25871238
TI  - Staggered parity-time-symmetric ladders with cubic nonlinearity.
AB  - We introduce a ladder-shaped chain with each rung carrying a parity-time- (PT-)
      symmetric gain-loss dimer. The polarity of the dimers is staggered along the
      chain, meaning alternation of gain-loss and loss-gain rungs. This structure,
      which can be implemented as an optical waveguide array, is the simplest one which
      renders the system PT-symmetric in both horizontal and vertical directions. The
      system is governed by a pair of linearly coupled discrete nonlinear Schrodinger
      equations with self-focusing or defocusing cubic onsite nonlinearity. Starting
      from the analytically tractable anticontinuum limit of uncoupled rungs and using
      the Newton's method for continuation of the solutions with the increase of the
      inter-rung coupling, we construct families of PT-symmetric discrete solitons and
      identify their stability regions. Waveforms stemming from a single excited rung
      and double ones are identified. Dynamics of unstable solitons is investigated
      too. 

PMID- 25871239
TI  - Wave propagation in granular chains with local resonances.
AB  - We study wave propagation in a chain of spherical particles containing a local
      resonator. The resonant particles are made of an aluminum outer spherical shell
      and a steel inner mass connected by a polymeric plastic structure acting as a
      spring. We characterize the dynamic response of individual particles and the
      transmitted linear spectra of a chain of particles in contact. A wide band gap is
      observed both in theoretical and experimental results. We show the ability to
      tune the acoustic transmission by varying the contact interaction between
      particles. Higher driving amplitude leads to the generation of nonlinearities
      both in the response of a single particle and that of the whole chain. For a
      single resonant particle, we observe experimentally a resonant frequency
      downshift, which follows a complex nonlinear behavior. In the chain of particles,
      nonlinearity leads to the generation of nonlinear harmonics and the presence of
      localized modes inside the band gap. 

PMID- 25871240
TI  - Modified momentum exchange method for fluid-particle interactions in the lattice
      Boltzmann method.
AB  - In this paper, a modified momentum exchange method for fluid-particle
      interactions is proposed based on the finite-volume lattice Boltzmann method. The
      idea of the improvement is to remove the restriction that the boundary points
      must be set as the midpoints of the grid lines or the intersection of the grid
      lines with the solid boundaries. The particle surface is represented by a set of
      arc (area) elements, and the interior fluid is used which the geometric
      conservation law is naturally satisfied. The interactions between fluid and arc
      (area) elements of particle boundary are considered using the momentum exchange
      method, and the mass of the fluid particles which collide with an arc (area)
      element is obtained by means of numerical integration in the control volume. The
      fluid field is corrected with the help of the smooth kernel function. Moreover, a
      generalized explicit time marching scheme is introduced to resolve the motion of
      particle in the problems with the ratio of particle density to fluid density is
      close to or less than 1. Finally, some numerical case studies of particle
      sedimentation are carried out to validate the present method. The corresponding
      results have a good agreement with the previous literature, which strongly
      demonstrates the capability of the improved method. 

PMID- 25871241
TI  - Lattice Boltzmann model for the correct convection-diffusion equation with
      divergence-free velocity field.
AB  - A lattice Boltzmann (LB) model for the convection-diffusion equation (CDE) with
      divergence-free velocity field is proposed, and the Chapman-Enskog analysis shows
      that the CDE can be recovered correctly. In the present model, the convection
      term is treated as a source term in the lattice Boltzmann equation (LBE) rather
      than being directly recovered by LBE; thus the CDE is intrinsically solved as a
      pure diffusion equation with a corresponding source term. To avoid the adoption
      of a nonlocal finite-difference scheme for computing the convection term, a local
      scheme is developed based on the Chapman-Enskog analysis. Most importantly, by
      properly specifying the discrete source term in the moment space, the local
      scheme can reach the same order (E^{2}) at which the CDE is recovered by a LB
      model. Numerical tests, including a one-dimensional periodic problem, diffusion
      of a Gaussian hill, diffusion of a rectangular pulse, and natural convection in a
      square cavity, are carried out to verify the present model. Numerical results are
      satisfactorily consistent with analytical solutions or previous numerical
      results, and show higher accuracy due to the correct recovery of CDE. 

PMID- 25871242
TI  - Fokker-Planck model of hydrodynamics.
AB  - We present a phenomenological description of the hydrodynamics in terms of the
      Fokker-Planck (FP) equation for one-particle distribution function. Similar to
      the Boltzmann equation or the Bhatnager-Gross-Krook (BGK) model, this approach is
      thermodynamically consistent and has the H theorem. In this model, transport
      coefficients as well as the equation of state can be provided independently. This
      approach can be used as an alternate to BGK-based methods as well as the direct
      simulation Monte Carlo method for the gaseous flows. 

PMID- 25871243
TI  - Spin models in three dimensions: Adaptive lattice spacing.
AB  - Aiming at the study of critical phenomena in the presence of boundaries with a
      nontrivial shape we discuss how lattices with an adaptive lattice spacing can be
      implemented. Since the parameters of the Hamiltonian transform nontrivially under
      changes of the length scale, adapting the lattice spacing is much more difficult
      than in the case of the numerical solution of partial differential equations,
      where this method is common practice. Here we shall focus on the universality
      class of the three-dimensional Ising model. Our starting point is the improved
      Blume-Capel model on the simple cubic lattice. In our approach, the system is
      composed of sectors with lattice spacing a,2a,4a,.... We work out how parts of
      the lattice with lattice spacing a and 2a, respectively, can be coupled in a
      consistent way. Here, we restrict ourself to the case where the boundary between
      the sectors is perpendicular to one of the lattice axes. Based on the theory of
      defect planes one expects that it is sufficient to tune the coupling between
      these two regions. To this end we perform a finite-size scaling study. However,
      first numerical results show that slowly decaying corrections remain. It turns
      out that these corrections can be removed by adjusting the strength of the
      couplings within the boundary layers. As a benchmark, we simulate films with
      strongly symmetry breaking boundary conditions. We determine the magnetization
      profile and the thermodynamic Casimir force. For our largest thickness L0=64.5,
      we find that results obtained for the homogeneous system are nicely reproduced.

PMID- 25871244
TI  - Kinetic Monte Carlo algorithm for thermally induced breakdown of fiber bundles.
AB  - Fiber bundle models are one of the most fundamental modeling approaches for the
      investigation of the fracture of heterogeneous materials being able to capture a
      broad spectrum of damage mechanisms, loading conditions, and types of load
      sharing. In the framework of the fiber bundle model we introduce a kinetic Monte
      Carlo algorithm to investigate the thermally induced creep rupture of materials
      occurring under a constant external load. We demonstrate that the method
      overcomes several limitations of previous techniques and provides an efficient
      numerical framework at any load and temperature values. We show for both equal
      and localized load sharing that the computational time does not depend on the
      temperature; it is solely determined by the external load and the system size. In
      the limit of low load where the lifetime of the system diverges, the
      computational time saturates to a constant value. The method takes into account
      the secondary failures induced by subsequent load redistributions after breaking
      events, with the additional advantage that breaking avalanches always start from
      a single broken fiber. 

PMID- 25871245
TI  - Counter-extrapolation method for conjugate interfaces in computational heat and
      mass transfer.
AB  - In this paper a conjugate interface method is developed by performing
      extrapolations along the normal direction. Compared to other existing conjugate
      models, our method has several technical advantages, including the simple and
      straightforward algorithm, accurate representation of the interface geometry,
      applicability to any interface-lattice relative orientation, and availability of
      the normal gradient. The model is validated by simulating the steady and unsteady
      convection-diffusion system with a flat interface and the steady diffusion system
      with a circular interface, and good agreement is observed when comparing the
      lattice Boltzmann results with respective analytical solutions. A more general
      system with unsteady convection-diffusion process and a curved interface, i.e.,
      the cooling process of a hot cylinder in a cold flow, is also simulated as an
      example to illustrate the practical usefulness of our model, and the effects of
      the cylinder heat capacity and thermal diffusivity on the cooling process are
      examined. Results show that the cylinder with a larger heat capacity can release
      more heat energy into the fluid and the cylinder temperature cools down slower,
      while the enhanced heat conduction inside the cylinder can facilitate the cooling
      process of the system. Although these findings appear obvious from physical
      principles, the confirming results demonstrates the application potential of our
      method in more complex systems. In addition, the basic idea and algorithm of the
      counter-extrapolation procedure presented here can be readily extended to other
      lattice Boltzmann models and even other computational technologies for heat and
      mass transfer systems. 

PMID- 25871246
TI  - Theory and application of shapelets to the analysis of surface self-assembly
      imaging.
AB  - A method for quantitative analysis of local pattern strength and defects in
      surface self-assembly imaging is presented and applied to images of stripe and
      hexagonal ordered domains. The presented method uses "shapelet" functions which
      were originally developed for quantitative analysis of images of galaxies
      (?10(20)m). In this work, they are used instead to quantify the presence of
      translational order in surface self-assembled films (?10(-9)m) through
      reformulation into "steerable" filters. The resulting method is computationally
      efficient (with respect to the number of filter evaluations), robust to variation
      in pattern feature shape, and, unlike previous approaches, is applicable to a
      wide variety of pattern types. An application of the method is presented which
      uses a nearest-neighbor analysis to distinguish between uniform (defect-free) and
      nonuniform (strained, defect-containing) regions within imaged self-assembled
      domains, both with striped and hexagonal patterns.

PMID- 25871247
TI  - Extended canonical Monte Carlo methods: Improving accuracy of microcanonical
      calculations using a reweighting technique.
AB  - Velazquez and Curilef [J. Stat. Mech. (2010); J. Stat. Mech. (2010)] have
      proposed a methodology to extend Monte Carlo algorithms that are based on
      canonical ensemble. According to our previous study, their proposal allows us to
      overcome slow sampling problems in systems that undergo any type of temperature
      driven phase transition. After a comprehensive review about ideas and connections
      of this framework, we discuss the application of a reweighting technique to
      improve the accuracy of microcanonical calculations, specifically, the well-known
      multihistograms method of Ferrenberg and Swendsen [Phys. Rev. Lett. 63, 1195
      (1989)]. As an example of application, we reconsider the study of the four-state
      Potts model on the square lattice L*L with periodic boundary conditions. This
      analysis allows us to detect the existence of a very small latent heat per site
      qL during the occurrence of temperature-driven phase transition of this model,
      whose size dependence seems to follow a power law qL(L)?(1/L)z with exponent
      z?0.26+/-0.02. Discussed is the compatibility of these results with the
      continuous character of temperature-driven phase transition when L->+infinity.

PMID- 25871248
TI  - Bulk viscosity of multiparticle collision dynamics fluids.
AB  - We determine the viscosity parameters of the multiparticle collision dynamics
      (MPC) approach, a particle-based mesoscale hydrodynamic simulation method for
      fluids. We perform analytical calculations and verify our results by simulations.
      The stochastic rotation dynamics and the Andersen thermostat variant of MPC are
      considered, both with and without angular momentum conservation. As an important
      result, we find a nonzero bulk viscosity for every MPC version. The explicit
      calculation shows that the bulk viscosity is determined solely by the collisional
      interactions of MPC. 

PMID- 25871249
TI  - Simple calculation of ab initio melting curves: Application to aluminum.
AB  - We present a simple, fast, and promising method to compute the melting curves of
      materials with ab initio molecular dynamics. It is based on the two-phase
      thermodynamic model of Lin et al [J. Chem. Phys. 119, 11792 (2003)] and its
      improved version given by Desjarlais [Phys. Rev. E 88, 062145 (2013)]. In this
      model, the velocity autocorrelation function is utilized to calculate the
      contribution of the nuclei motion to the entropy of the solid and liquid phases.
      It is then possible to find the thermodynamic conditions of equal Gibbs free
      energy between these phases, defining the melting curve. The first benchmark on
      the face-centered cubic melting curve of aluminum from 0 to 300 GPa demonstrates
      how to obtain an accuracy of 5%-10%, comparable to the most sophisticated
      methods, for a much lower computational cost.

PMID- 25871250
TI  - Simulation of protein association: Kinetic pathways towards crystal contacts.
AB  - We conducted molecular dynamics simulations combined with distance-based umbrella
      sampling and forward flux sampling to investigate the early stages of protein
      crystallization. Formation of contacts with long-range interactions and/or an
      exposed position on the protein surface was kinetically preferred over more
      stable hydrophobic contacts with a shorter attractive range, while the
      thermodynamic stability of the protein crystal was provided by hydrophobic
      interactions. Contacts with a large interaction area showed complex dissociation
      pathways that were not detected by distance-based umbrella sampling. Instead,
      forward flux sampling simulations of contact dissociation identified long-range
      attractive interactions. 

PMID- 25871251
TI  - Galilean-invariant Nose-Hoover-type thermostats.
AB  - A new pairwise Nose-Hoover type thermostat for molecular dynamics (MD)
      simulations which is similar in construction to the pair-velocity thermostat of
      Allen and Schmid, [Mol. Simul. 33, 21 (2007)] (AS) but is based on the
      configurational thermostat is proposed and tested. Both thermostats generate the
      canonical velocity distribution, are Galilean invariant, and conserve linear and
      angular momentum. The unique feature of the pairwise thermostats is an
      unconditional conservation of the total angular momentum, which is important for
      thermalizing isolated systems and those nonequilibrium bulk systems manifesting
      local rotating currents. These thermostats were benchmarked against the
      corresponding Nose-Hoover (NH) and Braga-Travis prescriptions, being based on the
      kinetic and configurational definitions of temperature, respectively. Some
      differences between the shear-rate-dependent shear viscosity from Sllod
      nonequilibrium MD are observed at high shear rates using the different
      thermostats. The thermostats based on the configurational temperature produced
      very similar monotically decaying shear viscosity (shear thinning) with
      increasing shear rate, while the NH method showed discontinuous shear thinning
      into a string phase, and the AS method produced a continuous increase of
      viscosity (shear thickening), after a shear thinning region at lower shear rates.
      Both pairwise additive thermostats are neither purely kinetic nor configurational
      in definition, and possible directions for further improvement in certain aspects
      are discussed.

PMID- 25871252
TI  - Discrete unified gas kinetic scheme for all Knudsen number flows. II. Thermal
      compressible case.
AB  - This paper is a continuation of our work on the development of multiscale
      numerical scheme from low-speed isothermal flow to compressible flows at high
      Mach numbers. In our earlier work [Z. L. Guo et al., Phys. Rev. E 88, 033305
      (2013)], a discrete unified gas kinetic scheme (DUGKS) was developed for low
      speed flows in which the Mach number is small so that the flow is nearly
      incompressible. In the current work, we extend the scheme to compressible flows
      with the inclusion of thermal effect and shock discontinuity based on the gas
      kinetic Shakhov model. This method is an explicit finite-volume scheme with the
      coupling of particle transport and collision in the flux evaluation at a cell
      interface. As a result, the time step of the method is not limited by the
      particle collision time. With the variation of the ratio between the time step
      and particle collision time, the scheme is an asymptotic preserving (AP) method,
      where both the Chapman-Enskog expansion for the Navier-Stokes solution in the
      continuum regime and the free transport mechanism in the rarefied limit can be
      precisely recovered with a second-order accuracy in both space and time. The
      DUGKS is an idealized multiscale method for all Knudsen number flow simulations.
      A number of numerical tests, including the shock structure problem, the Sod tube
      problem in a whole range of degree of rarefaction, and the two-dimensional
      Riemann problem in both continuum and rarefied regimes, are performed to validate
      the scheme. Comparisons with the results of direct simulation Monte Carlo (DSMC)
      and other benchmark data demonstrate that the DUGKS is a reliable and efficient
      method for multiscale flow problems.

PMID- 25871253
TI  - Comment on "Dynamic transition of supercritical hydrogen: Defining the boundary
      between interior and atmosphere in gas giants".
AB  - Trachenko et al. [Phys. Rev. E 89, 032126 (2014)] have argued for the existence
      of a "Frenkel line" in fluid hydrogen that separates "rigid" and "nonrigid"
      regimes in a supercritical region. On that basis, they proposed a criterion for
      locating the boundary between the interior and the atmosphere for gas giants.
      This Comment shows that the two methods they use to locate the transition between
      the rigid and nonrigid states are both questionable, which casts doubt on the
      claims in the paper.

PMID- 25871254
TI  - Reply to "Comment on 'Dynamic transition of supercritical hydrogen: Defining the
      boundary between interior and atmosphere in gas giants' ".
AB  - We have recently proposed the dynamic transition of molecular hydrogen in gas
      giants around 10 GPa based on the recent understanding of a supercritical state
      related to the Frenkel line. In the preceding Comment, Bryk makes several remarks
      with regard to the Frenkel line and its relationship to the speed of sound. We
      disagree with this discussion and respond to it in this Reply. 

PMID- 25871255
TI  - Comment on "Acoustical observation of bubble oscillations induced by bubble
      popping".
AB  - We have reproduced the experiment of acoustic monitoring of spontaneous popping
      of single soap bubbles standing in air reported by Ding et al. [2aaPhys. Rev. E
      75, 041601 (2007)]. By using a single microphone and two different signal
      acquisition systems recording in parallel the signal at the microphone output,
      among them the system used by Ding et al., we have experimentally evidenced that
      the acoustic precursors of bubble popping events detected by Ding et al. actually
      result from an acausal artifact of the signal processing performed by their
      acquisition system which lies outside of its prescribed working frequency range.
      No acoustic precursor of popping could be evidenced with the microphone used in
      these experiments, whose sensitivity is 1VPa-1 and frequency range is 500 Hz-100
      kHz.

PMID- 25871256
TI  - Reply to "Comment on 'Acoustical observation of bubble oscillations induced by
      bubble popping' ".
AB  - We reported on the sound pressure generated by aqueous foam bursts in our paper
      [Ding et al., Phys. Rev. E 75, 041601 (2007)]. Blanc et al., [Phys. Rev. E 91,
      036401 (2015)] found that sound from one of three mechanisms of bubble burst (the
      prepopping) actually results from an acausal artifact of the signal processing
      performed by their acquisition system which lies outside of its prescribed
      working frequency range. We examined the same hardware used in our paper and
      found that the frequency range is not the cause of the artifact. The prepopping
      sound was a result from a built-in finite impulse response filter of analog-to
      digital converters in the Bruel & Kjaer data acquisition system.

PMID- 25871257
TI  - Comment on "Exploring chaos in the Dicke model using ground-state fidelity and
      Loschmidt echo".
AB  - In a recent paper [Phys. Rev. E 90, 022920 (2014)] a study of the ground-state
      fidelity of the Dicke model as a function of the coupling parameter is presented.
      Abrupt jumps of the fidelity in the superradiant phase are observed and are
      assumed to be related to the transition to chaos. We show that this conclusion
      results from a misinterpretation of the numerics. In fact, if the parity symmetry
      is taken into account, the unexpected jumps disappear.

PMID- 25871258
TI  - Reply to "Comment on 'Exploring chaos in the Dicke model using ground-state
      fidelity and Loschmidt echo' ".
AB  - Although we agree with the fact reported in Garcia-Mata et al. [Phys. Rev. E 91,
      036901 (2015)] that a computational error resulted in misinterpretation of the
      behavior of the ground-state fidelity only, we emphasize below that this does not
      alter the main conclusion of our paper. That is the main claim that we had made
      about the use of quantum information measures to study chaos in the Dicke model
      still holds true.

PMID- 25871260
TI  - Wear particles promote reactive oxygen species-mediated inflammation via the
      nicotinamide adenine dinucleotide phosphate oxidase pathway in macrophages
      surrounding loosened implants.
AB  - BACKGROUND/AIMS: Prosthesis loosening is closely associated with chronic
      inflammatory cytokine secretion by macrophages, which are activated by wear
      particles or inflammatory stimulants such as lipopolysaccharide (LPS). Reactive
      oxygen species (ROS) are critical regulators of inflammation, but their enzymatic
      sources in response to wear particles and their effects on peri-implant LPS
      tolerance remain unclear. METHODS: Three ROS-related enzymes-nicotinamide adenine
      dinucleotide phosphate oxidase (NOX)-1 and -2 and catalase-were investigated in
      interface membrane tissues and in titanium (Ti) particle-stimulated macrophages
      in vitro. The generation of ROS and downstream inflammatory effects were measured
      with or without pre-incubation with apocynin, an NOX inhibitor. RESULTS: Pre
      exposure to Ti particles attenuated NF-kappaB activation in LPS-stimulated
      macrophages, indicating that wear particles suppress immune response, which may
      lead to chronic inflammation. NOX-1 and -2 were highly expressed in aseptically
      loosened interface membranes and in macrophages stimulated with Ti particles; the
      particles induced a moderate amount of ROS generation, NF-kappaB activation, and
      TNF-alpha secretion in macrophages, and these effects were suppressed by
      apocynin. CONCLUSION: Wear particles induce ROS generation through the NOX
      signaling pathway, resulting in persistent inflammation and delayed loosening.
      Thus, the suppression of NOX activity may be a useful strategy for preventing
      prosthesis loosening.

PMID- 25871261
TI  - Polycyclic Polyprenylated Acylphloroglucinol Congeners Possessing Diverse
      Structures from Hypericum henryi.
AB  - Polycyclic polyprenylated acylphloroglucinols (PPAPs) are a class of hybrid
      natural products sharing the mevalonate/methylerythritol phosphate and polyketide
      biosynthetic pathways and showing considerable structural and bioactive
      diversity. In a systematic phytochemical investigation of Hypericum henryi, 40
      PPAP-type derivatives, including the new compounds hyphenrones G-Q, were
      obtained. These compounds represent 12 different structural types, including four
      unusual skeletons exemplified by 5, 8, 10, and 17. The 12 different core
      structures found are explicable in terms of their biosynthetic origin. The
      structure of a known PPAP, perforatumone, was revised to hyphenrone A (5) by NMR
      spectroscopic and biomimetic synthesis methods. Several compounds exhibited
      inhibitory activities against acetylcholinesterase and human tumor cell lines.
      This study deals with the structural diversity, function, and biogenesis of
      natural PPAPs. 

PMID- 25871262
TI  - Adsorption of water and butanol in silicalite-1 film studied with in situ
      attenuated total reflectance-Fourier transform infrared spectroscopy.
AB  - Biobutanol produced by, e.g., acetone-butanol-ethanol (ABE) fermentation is a
      promising alternative to petroleum-based chemicals as, e.g., solvent and fuel.
      Recovery of butanol from dilute fermentation broths by hydrophobic membranes and
      adsorbents has been identified as a promising route. In this work, the adsorption
      of water and butanol vapor in a silicalite-1 film was studied using in situ
      attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy
      to better understand the adsorption properties of silicalite-1 membranes and
      adsorbents. Single-component adsorption isotherms were determined in the
      temperature range of 35-120  degrees C, and the Langmuir model was successfully
      fitted to the experimental data. The adsorption of butanol is very favorable
      compared to that of water. When the silicalite-1 film was exposed to a
      butanol/water vapor mixture with 15 mol % butanol (which is the vapor composition
      of an aqueous solution containing 2 wt % butanol, a typical concentration in an
      ABE fermentation broth, i.e., the composition of the gas obtained from gas
      stripping of an ABE broth) at 35  degrees C, the adsorption selectivity toward
      butanol was as high as 107. These results confirm that silicalite-1 quite
      selectively adsorbs hydrocarbons from vapor mixtures. To the best of our
      knowledge, this is the first comprehensive study on the adsorption of water and
      butanol in silicalite-1 from vapor phase. 

PMID- 25871263
TI  - Men's strategies for preserving emotional well-being in advanced prostate cancer:
      An interpretative phenomenological analysis.
AB  - OBJECTIVE: This study explores men with advanced prostate cancers' own practices
      for promoting and maintaining emotional well-being using Interpretative
      Phenomenological Analysis. DESIGN: Five men with advanced prostate cancer
      participated in face-to-face, semi-structured, in-depth interviews. RESULTS:
      Within rich narratives of lost and regained well-being, two super-ordinate themes
      emerged--'living with an imminent and uncertain death' and 'holding on to life.'
      Well-being was threatened by reduced sense of the future, isolation and
      uncertainty. Yet, the men pursued well-being by managing their emotions, striving
      for the future whilst enjoying life in the present, taking care of their families
      and renegotiating purpose. Running through participant's accounts was a
      preference for taking action and problem-solving. Sense of purpose, social
      connectedness, and life engagement were revealed as concepts central to improving
      well-being, indicating areas which practitioners could explore with men to help
      them re-establish personal goals and life purpose. CONCLUSIONS: The findings also
      add weight to the evidence base for the potential value of psychological
      interventions such as cognitive behaviour therapy and mindfulness in men with
      prostate cancer.

PMID- 25871264
TI  - Local Structure and Dynamics of Hydration Water in Intrinsically Disordered
      Proteins.
AB  - Hydration water around protein surface plays a key role in structure, folding and
      dynamics of proteins. Intrinsically disordered proteins lack secondary and/or
      tertiary structure in their native state. Thus, characterizing the local
      structure and dynamics of hydration water around disordered proteins is
      challenging for both experimentalists and theoreticians. The local structure,
      orientation and dynamics of hydration water in the vicinity of intrinsically
      disordered proteins is investigated through molecular dynamics simulations. The
      analysis of the hydration capacity reveals that the disordered proteins have much
      larger binding capacity for hydration water than globular proteins. The surface
      and radial distribution of water molecules around the disordered proteins depict
      a similar trend. The local structure of the hydration water evaluated in terms of
      the tetrahedral order parameter, shows a higher order among the water molecules
      surrounding disordered proteins/regions. The residence time of water molecules
      clearly exhibits slow dynamics of hydration water around the surface of
      disordered proteins/regions as compared to globular proteins. The orientation of
      water molecules is found to be distinctly different for ordered and disordered
      proteins/regions. This analysis provides a better insight into the structure and
      dynamics of hydration water around disordered proteins. 

PMID- 25871265
TI  - Primary Yolk Sac Tumor of the Prostate: A Case Report and Review of the
      Literature.
AB  - Endodermal sinus (yolk sac) tumors (ESTs) are rare neoplasms that most commonly
      arise in the ovaries or testis. Only six cases of prostatic ESTs have been
      reported in the literature. We report a case of prostatic EST, the first case in
      which the patient had a history of previous testis cancer. Treatment included
      cisplatin-based chemotherapy and radical prostatectomy. Previous cases of primary
      ESTs and use of cisplatin-based therapy as well as metastatic tumors to the
      prostate are discussed. 

PMID- 25871266
TI  - Long-term population effect of male circumcision in generalised HIV epidemics in
      sub-Saharan Africa.
AB  - This paper examines the complex relationship between male circumcision and HIV
      prevalence and incidence in sub-Saharan African countries that have generalised
      epidemics. In South Africa, the mean yearly HIV incidence and an estimate of the
      net reproduction rate of the epidemic (R 0) (in this case, the ratio of the
      number of HIV-infected persons between 1994 and 2004 to the number of persons
      infected in 1994 from which they were presumed to have become infected) were
      computed from antenatal clinic data for the period 1994-2004, and then compared,
      by province, to prevailing levels of male circumcision (high, medium and low). In
      South Africa, mean yearly HIV incidence and net reproduction rate of the epidemic
      were not lower in provinces with higher levels of male circumcision. For thirteen
      other countries where Demographic and Health Survey data were available, male HIV
      prevalence in circumcised and non-circumcised groups was compared. A meta
      analysis of that data, contrasting male HIV seroprevalence according to
      circumcision status, showed no difference between the two groups (combined risk
      ratio [RR] = 0.99, 95% CI = 0.94-1.05). Individual case study analysis of eight
      of those countries showed no significant difference in seroprevalence in
      circumcised and uncircumcised groups, while two countries (Kenya and Uganda)
      showed lower HIV prevalence among circumcised groups, and three countries
      (Cameroon, Lesotho and Malawi) showed higher HIV prevalence among circumcised
      groups. In most countries with a complex ethnic fabric, the relationship between
      men's circumcision status and HIV seroprevalence was not straightforward, with
      the exception of the Luo in Kenya and a few groups in Uganda. These observations
      put into question the potential long-term effect of voluntary circumcision
      programmes in countries with generalised HIV epidemics. 

PMID- 25871267
TI  - Gender, famine and HIV/AIDS: rethinking new variant famine in Malawi.
AB  - Although making a large and rapid impact on our understandings of the
      interactions between famine and HIV/AIDS, the new variant famine hypothesis has
      had little critical scrutiny. This paper uses a case study of the Malawian food
      crisis of 2001/2002 to contribute to understandings of new variant famine (NVF).
      The critical approach argues that a consideration for gender - the socially
      constructed relationship between men and women - needs to be central to
      understanding the interactions between HIV/AIDS and famine, which the NVF
      hypothesis seeks to explain. Evidence from the Malawian crisis is highly
      suggestive, although not conclusive, that NVF is best understood as mediated by
      gender inequalities. 

PMID- 25871268
TI  - Rationing access to public-sector antiretroviral treatment during scale-up in
      South Africa: implications for equity.
AB  - As with other large-scale antiretroviral therapy (ART) programmes initiated in
      developing countries, rationing of ART in South Africa was inevitable in the face
      of limited human and infrastructural resources. This paper discusses rationing of
      ART and its implications for equity in South Africa, with a particular emphasis
      on the national programme in the Free State Province. We examine both the
      explicit and implicit dimensions of ART rationing, while considering the content
      of policy, programme design and implementation processes. The explicit rationing
      criteria included in the national comprehensive plan, as well as the associated
      treatment guidelines, direct and influence rationing decisions practised locally.
      However, implicit processes of rationing, which limit demand, are also wittingly
      and unwittingly introduced in several ways, and at all levels of the health
      service. Consequences of rationing manifest in the high numbers of patients lost
      to the system and the difficulties faced by the most impoverished clients in
      gaining access to ART services on an ongoing basis. Not losing sight of the
      equity element within rationing is important, and this aspect will have to be
      formally monitored for eventual success of the country's ART programme. ART roll
      out processes also require ongoing efforts to build consensus and confidence in
      rationing, accomplished with a view to optimal fairness. 

PMID- 25871269
TI  - Cognitive dissonance as an explanation of the genesis, evolution and persistence
      of Thabo Mbeki's HIV denialism.
AB  - The ongoing damage that the newer forms of HIV denialism are visiting upon our
      country is evidenced by the recent firing of Nozizwe Madlala-Routledge, the South
      African Deputy Minister of Health. It is widely believed that the underlying
      reason for her dismissal was her support of orthodox HIV treatment and prevention
      strategies and her disdain for HIV denialism. This paper seeks to understand the
      origins, spread and metamorphosis of President Thabo Mbeki's HIV denialism in
      South Africa. Using the theory of cognitive dissonance, I argue that, given the
      structural beliefs of the African National Congress (ANC) and the pattern of
      emergence of HIV in the 1980s, a degree of scepticism around the putative science
      of HIV was probable in ANC circles. On assuming the Presidency in 1999, Mbeki
      tapped into this scepticism to formulate his initial biological version of HIV
      denialism, which claimed that 'a virus can't cause a syndrome.' The steady
      erosion of support for this flagrant HIV denialism, together with the rise of
      neoliberal thinking in the ANC, would lead to the evolution of this biological
      denialism into a form of treatment denialism. This ideology argued against the
      widespread provision and use of antiretroviral treatment. Empirical evidence is
      presented to demonstrate the extent to which ongoing HIV denial in the general
      population is continuing to fuel the spread of HIV. 

PMID- 25871270
TI  - Reasons for multiple sexual partnerships: perspectives of young people in Zambia.
AB  - Epidemiological evidence so far suggests that multiple sexual partnerships are an
      important factor driving the HIV epidemic. Recently, there has been renewed
      emphasis on fidelity and partner-reduction in preventing HIV infections. Like
      many countries in sub-Saharan Africa, Zambia is facing a severe HIV epidemic and
      young people are heavily affected. This study explores youths' perspectives on
      multiple sexual partnerships in the context of HIV and AIDS. The study draws on
      four focus group discussions and 10 in-depth interviews with university students
      in Lusaka, Zambia, in 2006. While the young people were generally aware of the
      HIV-related risk associated with multiple sexual partnerships, they felt several
      obstacles prevented them from changing their sexual behaviour. Of special
      interest are their perceptions related to socio-economic disadvantages and
      cultural factors. 

PMID- 25871271
TI  - Building partnerships to support community-led HIV/AIDS management: a case study
      from rural South Africa.
AB  - The importance of partnerships between marginalised communities and support
      agencies (from the public sector, private sector and civil society) is a pillar
      of HIV/AIDS management policy. Such alliances are notoriously difficult to
      promote and sustain. We present a case study focusing on the first stage of a
      project seeking to build partnerships to facilitate local responses to HIV/AIDS
      in a remote rural community in South Africa. To date the Entabeni project has
      been successful in its goal of training volunteer health workers in home-based
      care, peer education, project management and procedures for accessing grants and
      services. The paper focuses on the project's other goal - to create external
      support structures for these volunteers (drawing on government departments, local
      NGOs and private-sector philanthropists). The partnership aims to empower
      volunteers to lead HIV-prevention and AIDS-care efforts, and to make public
      services more responsive to local needs. We illustrate how features of the local
      public-sector environment have actively worked against effective community
      empowerment. These include a rigid hierarchy, poor communication between senior
      and junior health professionals, lack of social development skills and the
      demoralisation and/or exhaustion of public servants dealing with multiple social
      problems in under-resourced settings. We outline the obstacles that have
      prevented private-sector involvement, suggesting a degree of scepticism about the
      potential for private-sector contributions to development in remote areas. We
      discuss how the project's most effective partners have been two small under
      funded NGOs - run by highly committed individuals with a keen understanding of
      social-development principles, flexible working styles and a willingness to work
      hard for small gains. Despite many challenges, the partnership formation process
      has seen some positive achievements; we outline these and discuss the essential
      role played by an external change agent, and conclude with a discussion of the
      possibility of building long-term structures to sustain the project. 

PMID- 25871272
TI  - Growth, productivity, and scientific impact of sources of HIV/AIDS research
      information, with a focus on eastern and southern Africa.
AB  - As channels of communicating HIV/AIDS research information, serial publications
      and particularly journals are increasingly used in response to the pandemic. The
      last few decades have witnessed a proliferation of sources of HIV/AIDS-related
      information, bringing many challenges to collection-development librarians as
      well as to researchers. This study uses an informetric approach to examine the
      growth, productivity and scientific impact of these sources, during the period
      1980 to 2005, and especially to measure performance in the publication and
      dissemination of HIV/AIDS research about or from eastern or southern Africa. Data
      were collected from MEDLINE, Science Citation Index (SCI), Social Sciences
      Citation Index (SSCI), and Ulrich's Periodical Directory. The analysis used
      Sitkis version 1.5, Microsoft Office Access, Microsoft Office Excel, Bibexcel,
      and Citespace version 2.0.1. The specific objectives were to identify the number
      of sources of HIV/AIDS-related information that have been published in the
      region, the coverage of these in key bibliographic databases, the most commonly
      used publication type for HIV/AIDS research, the countries in which the sources
      are published, the sources' productivity in terms of numbers of papers and
      citations, the most influential sources, the subject coverage of the sources, and
      the core sources of HIV/AIDS-information. 

PMID- 25871273
TI  - Higher-risk sexual behaviour among HIV patients receiving antiretroviral
      treatment in Ibadan, Nigeria.
AB  - A stress-coping model was tested to examine the role that negative life events,
      coping methods, and depression might play in moderating the associations between
      HIV-related factors (ARV drug regimen, HIV staging and CD4 count) and higher-risk
      sexual behaviours of people living with HIV/AIDS. The model depicted hypothesised
      relationships among several characteristics of HIV-related variables, negative
      life events, coping behaviours and depression. One hundred and fifty-four HIV
      patients who were receiving antiretroviral therapy through the PEPFAR programme
      in Ibadan, Nigeria, responded to a questionnaire. In a hierarchical multiple
      regression analysis, variables were entered into the equation in the order
      specified a priori by the model. The results show that: (a) patients on the
      combined 3-drug ARV regimen were more likely to have engaged in higher-risk
      sexual behaviours as compared to those on a regimen of two or one ARV drugs; (b)
      negative life events and (c) a coping method characterised by HIV-status denial
      both predicted increased higher-risk-sexual-behaviour practice among the
      patients. The study underscores the need for continuous evaluation of the level
      of higher-risk-sexual-behaviour practice and associated factors, particularly
      among HIV/AIDS patients receiving ARV treatment. 

PMID- 25871274
TI  - Perspectives of South African school children on HIV/AIDS, and the implications
      for education programmes.
AB  - The study explores and describes South African school children's perspectives of
      HIV and AIDS, and links this to their respective cognitive developmental stage.
      The paper highlights developmental differences in the children's perceptions of
      HIV or AIDS and makes specific recommendations for improving HIV/AIDS education
      in school. A questionnaire of mainly open-ended questions was used to survey the
      HIV/AIDS-related perceptions of 1 904 school-going children aged 6 to 19 years.
      In-depth content analyses as well as basic statistical analyses were performed on
      the data. Although the school children had a good basic knowledge of HIV/AIDS and
      generally positive attitudes towards HIV and AIDS, they believed many
      misconceptions and myths. The children were mostly very afraid of HIV or AIDS and
      felt extremely vulnerable to HIV infection. The particular developmental phase
      was the strongest predictor of a child's understanding of HIV/AIDS. The findings
      have been used to formulate guidelines for the development or enhancement of age
      appropriate HIV/AIDS education programmes or curricula in schools. It is hoped
      that teachers, educators and youth workers will use these findings to re-evaluate
      and adjust their HIV/AIDS education programmes and messages to fit the needs of
      the young people in their care. 

PMID- 25871275
TI  - Parental communication with children about sex in the South African HIV epidemic:
      raced, classed and cultural appropriations of Lovelines.
AB  - Responsive to perceived high risk of HIV infection by sexually active youth,
      several South African sexual health-promotion campaigns have used media targeting
      mothers, instructing them on how sex should be talked about with their children
      to 'risk-proof' them. A Foucauldian approach to the normative apparatus of family
      sexuality-risk finds mothers positioned as pivots between 'public' (health,
      economy, culture) and 'private' (family, childrearing, sex) apparatuses, tasked
      with appropriately socialising a new generation of sexually responsible, HIV-free
      citizens. This paper uses a reading of interactive discourse from (racially and
      gender) mixed groups of parents who, as professionals and postgraduate students
      in a university context, discussed their own childrearing practices in response
      to a particular didactic media text about sex-communication. In a way different
      from traditional media-reception studies, this discourse analytic reading of
      parents' engagement with risk-expertise examines how mothers especially are
      persuaded (or not) to adopt particular childrearing practices in the context of
      an HIV epidemic. Using a Foucauldian argument about subject positioning, this
      paper examines how the parents positioned themselves in relation to the expertise
      offered in the stimulus material, as well as how they positioned one another
      during the group discussions. The analysis explores the partial buy-in to expert
      Western psychological techniques concerning talking with children about sex
      openly and often, and how this appropriation is negotiated in contextual family
      situations that are gendered, raced, classed and acculturated. 

PMID- 25871276
TI  - HIV- and AIDS-related (mis)perceptions and (non)responses of school principals in
      the Eastern Cape, South Africa.
AB  - Despite various HIV and AIDS training programmes offered for educators by the
      South African Department of Education, little has been achieved at the level of
      management in terms of creating a wider understanding of the social and cultural
      complexities of the condition and its impact on the quality of teaching and
      learning. Specifically, there is a lack of developmental programmes to help
      school principals provide leadership that can ensure that teachers and children
      who live in a context affected by the disease will still find themselves in a
      school environment of quality, care and compassion. With this in mind, we
      conducted a qualitative research enquiry among a sample of 12 school principals
      in the Eastern Cape Province in order to discover their perceptions about the
      impacts of HIV and AIDS on their schools and to learn how they have responded to
      the corresponding challenges. Our intention was to use the findings primarily to
      inform the development of an academic programme and short courses to empower
      school principals and leadership in this regard, but the findings may also be
      relevant as a guide for research on a larger scale. 

PMID- 25871277
TI  - Junior-headed households as a possible strategy for coping with the growing
      orphan crisis in northern Namibia.
AB  - This paper reports research concerning junior-headed households among Oshiwambo
      speakers in north-central Namibia. Based on field interviews with randomly
      sampled junior heads of households and selected key informants, we outline some
      features common to the junior-headed households and the ways in which they
      attempt to manage their lives. The concepts of child- and junior-headed
      households are also clarified. We argue that due to a significant increase in the
      number of orphans in Namibia, the ability of extended families to absorb and care
      for orphaned children is beginning to fail. Although child-headed households are
      still rare in Namibia, junior-headed households - those led by young persons aged
      18 years or more and who are unmarried and have not established a household of
      their own - appear to be more common. The paper poses the question, do junior
      headed households represent a coping strategy in a situation where the upper
      limits of the ability of extended families to absorb and provide care for orphans
      has been reached? The ability of junior heads of households to run their
      households and care for younger children is limited by lack of experience,
      unemployment, and poverty. The primary function of these juniors appears to be
      maintaining order and providing basic security against abuse and the grabbing of
      property. By and large, such households are dependent on handouts from
      neighbours, relatives and the church, for food, clothing and financial support.
      We propose that efforts be made to secure access to education for junior heads of
      households, and to develop ways of improving their knowledge and skills regarding
      both household management and income-generating activities. 

PMID- 25871278
TI  - The effectiveness of a national communication campaign using religious leaders to
      reduce HIV-related stigma in Ghana.
AB  - This article describes the effects of a national mass media and community-level
      stigma-reduction programme in Ghana, in which national and local religious
      leaders urged their congregations and the general public to have greater
      compassion for people living with HIV or AIDS (PLHA). Data were collected from
      men and women living in three regions, first in 2001 (n = 2 746) and again in
      2003 (n = 2 926). Attitudes related to a punitive response to PLHA both improved
      over time and were positively associated with exposure to the programme's
      campaign, controlling for potential confounding variables. Respondents in the
      2003 survey were 20% more likely than respondents in the 2001 survey to be
      willing to care for an HIV-infected relative in their own household and 40% more
      likely to believe that an HIV-infected female teacher should be allowed to
      continue teaching. Overall, respondents exposed to the campaign were 45% more
      likely than those not exposed to it to be willing to care for a HIV-infected
      relative, and 43% more likely to believe that an HIV-infected female teacher
      should be allowed to continue teaching. Respondents exposed to the campaign also
      had significantly more favourable scores on an attitude scale measuring the
      belief that HIV-infected individuals should be isolated from others. The results
      of this evaluation suggest that mass media channels and religious leaders can
      effectively address HIV-related stigma on a national scale. 

PMID- 25871279
TI  - Uptake of voluntary counselling and testing for HIV by pregnant women in a
      prevention-of-mother-to-child-transmission programme at Aminu Kano Teaching
      Hospital, Nigeria.
AB  - Mother-to-child transmission is the main mode of HIV infection among children in
      developing countries. In 2003, as a result of government policy, a prevention-of
      mother-to-child-transmission (PMTCT) programme was introduced at Aminu Kano
      Teaching Hospital in Nigeria. The aim of this study was to determine the pattern
      of voluntary counselling and testing (VCT) uptake and HIV seroprevalence among
      pregnant women using the service. VCT has become part of routine antenatal care
      at the hospital; in addition, antiretroviral prophylaxis/treatment, modification
      of obstetric practices, and counselling on infant feeding options are provided
      for HIV-positive pregnant women. Data on clients' socio-demographic
      characteristics, VCT uptake, and HIV seropositivity for a three-year period (from
      January 2004 to December 2006) were taken from nationally prepared PMTCT
      registers kept at the hospital, and prospectively entered into a database. During
      the period, 6 887 women newly accessed antenatal care (i.e. repeat pregnancies
      were excluded). All the women were group counselled, and 6 702 (97.3%) agreed to
      undergo HIV testing. Overall HIV prevalence among these pregnant women for the
      study period was 5.9% (95% CI 5.2-6.3%). The data have shown a statistically
      significant trend of rising HIV prevalence in this group: at 4.5%, prevalence was
      lowest in 2004; rose to 4.9% in 2005; and peaked at 7.6% in 2006 (chi(2) trend =
      21.9; p < 0.001). Overall HIV seroprevalence was 3.5% among 15- to 19-year-old
      women, 7% among 25- to 29-year-old women, and 4.5% among women over age 40. There
      was an inverse relationship between parity (number of children borne) and HIV
      seroprevalence such that women of low parity had high HIV prevalence, and vice
      versa (chi(2) trend = 13.1; p < 0.01). Respectively, 11.4%, 5.7%, and 5.5% of the
      pregnant women first using VCT in the first, second, and third trimesters of
      their pregnancy were found to be HIV-positive. All women testing HIV-positive
      were informed of their serostatus and the modes of preventing mother-to-child
      transmission of HIV. There is a relatively high uptake of VCT for PMTCT at this
      tertiary hospital, while an increasingly higher proportion of HIV-positive
      pregnant women are being identified and provided with opportunities to prevent
      HIV transmission to their babies. PMTCT should be universally accessible to women
      in developing countries. 

PMID- 25871280
TI  - Discourses of childhood innocence in primary school HIV/AIDS education in South
      Africa.
AB  - This article draws from interview data to examine the meanings that teachers in
      two race and class-specific contexts in greater Durban, South Africa, may give to
      children's right to sexual health information as a part of HIV/AIDS education.
      The article focuses on the regulation and production of childhood innocence by
      means of the ways the primary school teachers talked about sex in their HIV/AIDS
      education lessons to grade-four students. I argue that discourses of childhood
      innocence regulate and limit the possibilities of conversing about sex in such a
      context. The dominant discourses construct children as 'too young to know' and
      displace children's right to sexual health information to older children, while
      stressing anxieties about parent hostility to sex education, which precludes
      effective coverage of sexual topics in HIV/AIDS education. Showing how race,
      class and culture are deployed in upholding innocence, I contend that the notion
      of childhood innocence is embedded within the varying social contexts that make
      up the South African landscape. But, I suggest that an assumption that primary
      school teachers will engage with HIV/AIDS education while mediating information
      about sex in health promotion is simplistic. In conclusion, I propose a need for
      ongoing theoretical and practical work with teachers and the need to build
      alliances with parents. 

PMID- 25871281
TI  - The application of gold nanoparticles as a promising therapeutic approach in
      breast and ovarian cancer.
AB  - The development of specialized nanoparticles (NPs) for use in the detection and
      treatment of cancer is increasing. In the last few years, gold nanoparticles
      (AuNPs) have been greatly studied in biological and photothermal therapeutic
      status. AuNPs can bind to a wide range of organic molecules, and their synthesis
      is easy. In this review, we summarize the characteristics of AuNPs, their
      contributions to tumor destruction, their toxicity, and their potential in the
      treatment of breast and ovarian cancer. 

PMID- 25871282
TI  - Genetic influence on left ventricular structure and function: a Korean twin and
      family study.
AB  - Genetic factors have been suggested to be one of the determinants of the
      variation of left ventricular (LV) structure and function. However, the
      heritability range of LV structure varies across studies and the influence of
      genetics on LV function is not well established, especially in Asian populations.
      Study subjects were 1,642 healthy Korean adults from 426 families, consisting of
      298 pairs of monozygotic twins, 62 pairs of dizygotic twins, one set of triplets,
      567 siblings, and 354 parents. LV structure and function were measured by M-mode
      and 2D echocardiography, and conventional and tissue Doppler imaging (TDI).
      Pairwise intra-class correlations for various familial relationships and
      heritability were estimated for LV structure and function. The heritability of LV
      mass, LV ejection fraction (LVEF), left atrial volume index, the ratio between
      early and late diastolic velocity of mitral inflow (E/A ratio), and the ratio
      between early diastolic velocity of mitral inflow and early diastolic mitral
      annular velocities (E/Ea ratio) was 0.44, 0.27, 0.44, 0.25, and 0.33,
      respectively. Bivariate genetic analysis showed that LV structural and functional
      traits had significant genetic correlations with cardiovascular risk factors.
      Additive genetic correlation (rhoG) of LV mass with body mass index, systolic
      blood pressure, and high density lipoprotein cholesterol were 0.49, 0.42, and 
      0.15 respectively. LVEF (rhoG = 0.33) and left atrial volume index (rhoG = 0.24)
      also had a significant genetic correlation with systolic blood pressure. These
      findings support the theory that genetic factors have significant influence on
      these traits and necessitate further work to identify the specific genes
      involved. 

PMID- 25871283
TI  - Abstracts of presentations at the 2015 southern division meeting.

PMID- 25871284
TI  - Nucleation and Crystal Growth of Organic-Inorganic Lead Halide Perovskites under
      Different Relative Humidity.
AB  - Organic-inorganic lead halide perovskite compounds are very promising materials
      for high-efficiency perovskite solar cells. But how to fabricate high-quality
      perovksite films under controlled humidity conditions is still an important issue
      due to their sensitivity to moisture. In this study, we investigated the
      influence of ambient humidity on crystallization and surface morphology of one
      step spin-coated perovskite films, as well as the performance of solar cells
      based on these perovskite films. On the basis of experimental analyses and thin
      film growth theory, we conclude that the influence of ambient humidity on
      nucleation at spin-coating stage is quite different from that on crystal growth
      at annealing stage. At the spin-coating stage, high nucleation density induced by
      high supersaturation prefers to appear under anhydrous circumstances, resulting
      in layer growth and high coverage of perovskite films. But at the annealing
      stage, the modest supersaturation benefits formation of perovskite films with
      good crystallinity. The films spin-coated under low relative humidity (RH)
      followed by annealing under high RH show an increase of crystallinity and
      improved performance of devices. Therefore, a mechanism of fast nucleation
      followed by modest crystal growth (high supersaturation at spin-coating stage and
      modest supersaturation at annealing stage) is suggested in the formation of high
      quality perovskite films. 

PMID- 25871285
TI  - Multidimensional (0D to 3D) Alkaline-Earth Metal Diphosphonates: Synthesis,
      Structural Diversity, and Luminescence Properties.
AB  - A series of new alkaline-earth metal diphosphonate frameworks were successfully
      synthesized under solvothermal reaction condition (160  degrees C, 3 d) using 1
      hydroxyethylidene-1,1-diphosphonic acid (CH3C(OH)(H2PO3)2, hedpH4) as a
      diphosphonate building block and Mg(II), Ca(II), Sr(II), or Ba(II) ions as
      alkaline-earth metal ion centers in water, dimethylformamide, and/or EtOH media.
      These diphosphonate frameworks, (H2NMe2)4[Mg(hedpH2)3].3H2O (1),
      (H2NMe2)2[Ca(hedpH2)2] (2), (H2NMe2)2[Sr3(hedpH2)4(H2O)2] (3), and
      [Ba3(hedpH2)3].H2O (4) exhibited interesting structural topologies (zero-, one-,
      two-, and three-dimensional (0D, 1D, 2D, and 3D, respectively)), which are mainly
      depending on the metal ions and the solvents used in the synthesis. The single
      crystal analysis of these newly synthesized compounds revealed that 1 was a 0D
      molecule, 2 has 1D chains, 3 was a 3D molecule, and 4 has 2D layers. All
      compounds were further characterized using thermogravimetric analysis, solid
      state (31)P NMR, powder X-ray diffraction analysis, UV-vis spectra, and infrared
      spectroscopy. In addition, Eu(III)- and Tb(III)-doped compounds of 1-4, namely,
      (H2NMe2)4[Ln(x)Mg(1-x)(hedpH2)2(hedpH(2-x))].3H2O (1Ln), (H2NMe2)2[Ln(x)Ca(1
      x)(hedpH2)(hedpH(2-x))] (2Ln), (H2NMe2)2[Ln(x)Sr(3-x)(hedpH2)3(hedpH(2-x))(H2O)2]
      (3Ln), and [Ln(x)Ba(3-x)(hedpH2)2(hedpH(2-x))].H2O (4Ln) (where Ln = Eu, Tb),
      were synthesized, and their photoluminescence properties were studied. The
      quantum yield of 1Eu-4Eu was measured with reference to commercial red phosphor,
      Y2O2S:Eu(3+) (YE), and the quantum yield of terbium-doped compounds 1Tb-4Tb was
      measured with reference to commercial green-emitting phosphor CeMgAl10O17:Tb(3+).
      Interestingly, the compound 2Eu showed very high quantum yield of 92.2%, which is
      better than that of the reference commercial red phosphor, YE (90.8%).

PMID- 25871286
TI  - Inhibition of N-type calcium channels by fluorophenoxyanilide derivatives.
AB  - A set of fluorophenoxyanilides, designed to be simplified analogues of previously
      reported omega-conotoxin GVIA mimetics, were prepared and tested for N-type
      calcium channel inhibition in a SH-SY5Y neuroblastoma FLIPR assay. N-type or
      Cav2.2 channel is a validated target for the treatment of refractory chronic
      pain. Despite being significantly less complex than the originally designed
      mimetics, up to a seven-fold improvement in activity was observed. 

PMID- 25871287
TI  - Toxin profile of Gymnodinium catenatum (Dinophyceae) from the Portuguese coast,
      as determined by liquid chromatography tandem mass spectrometry.
AB  - The marine dinoflagellate Gymnodinium catenatum has been associated with
      paralytic shellfish poisoning (PSP) outbreaks in Portuguese waters for many
      years. PSP syndrome is caused by consumption of seafood contaminated with
      paralytic shellfish toxins (PSTs), a suite of potent neurotoxins. Gymnodinium
      catenatum was frequently reported along the Portuguese coast throughout the late
      1980s and early 1990s, but was absent between 1995 and 2005. Since this time, G.
      catenatum blooms have been recurrent, causing contamination of fishery resources
      along the Atlantic coast of Portugal. The aim of this study was to evaluate the
      toxin profile of G. catenatum isolated from the Portuguese coast before and after
      the 10-year hiatus to determine changes and potential impacts for the region.
      Hydrophilic interaction liquid chromatography tandem mass spectrometry (HILIC
      MS/MS) was utilized to determine the presence of any known and emerging PSTs in
      sample extracts. Several PST derivatives were identified, including the N
      sulfocarbamoyl analogues (C1-4), gonyautoxin 5 (GTX5), gonyautoxin 6 (GTX6), and
      decarbamoyl derivatives, decarbamoyl saxitoxin (dcSTX), decarbamoyl neosaxitoxin
      (dcNeo) and decarbamoyl gonyautoxin 3 (dcGTX3). In addition, three known hydroxy
      benzoate derivatives, G. catenatum toxin 1 (GC1), GC2 and GC3, were confirmed in
      cultured and wild strains of G. catenatum. Moreover, two presumed N-hydroxylated
      analogues of GC2 and GC3, designated GC5 and GC6, are reported. This work
      contributes to our understanding of the toxigenicity of G. catenatum in the
      coastal waters of Portugal and provides valuable information on emerging PST
      classes that may be relevant for routine monitoring programs tasked with the
      prevention and control of marine toxins in fish and shellfish. 

PMID- 25871288
TI  - Structural analysis and anticoagulant activities of the novel sulfated fucan
      possessing a regular well-defined repeating unit from sea cucumber.
AB  - Sulfated fucans, the complex polysaccharides, exhibit various biological
      activities. Herein, we purified two fucans from the sea cucumbers Holothuria
      edulis and Ludwigothurea grisea. Their structures were verified by means of
      HPGPC, FT-IR, GC-MS and NMR. As a result, a novel structural motif for this type
      of polymers is reported. The fucans have a unique structure composed of a central
      core of regular (1->2) and (1->3)-linked tetrasaccharide repeating units.
      Approximately 50% of the units from L. grisea (100% for H. edulis fucan) contain
      sides of oligosaccharides formed by nonsulfated fucose units linked to the O-4
      position of the central core. Anticoagulant activity assays indicate that the sea
      cucumber fucans strongly inhibit human blood clotting through the intrinsic
      pathways of the coagulation cascade. Moreover, the mechanism of anticoagulant
      action of the fucans is selective inhibition of thrombin activity by heparin
      cofactor II. The distinctive tetrasaccharide repeating units contribute to the
      anticoagulant action. Additionally, unlike the fucans from marine alga, although
      the sea cucumber fucans have great molecular weights and affluent sulfates, they
      do not induce platelet aggregation. Overall, our results may be helpful in
      understanding the structure-function relationships of the well-defined
      polysaccharides from invertebrate as new types of safer anticoagulants. 

PMID- 25871289
TI  - Studies toward the total synthesis of Itralamide B and biological evaluation of
      its structural analogs.
AB  - Itralamides A and B were isolated from the lipophilic extract of Lyngbya
      majuscula collected from the eastern Caribbean. Itralamide B (1) showed cytotoxic
      activity towards human embryonic kidney cells (HEK293, IC50 = 6 MUM). Preliminary
      studies disapproved the proposed stereochemistry of itralamide. In this paper, we
      will provide a full account of the total synthesis of four stereoisomers of
      itralamide B and the results derived from biological tests of these structural
      congeners. 

PMID- 25871290
TI  - Astaxanthin attenuates early acute kidney injury following severe burns in rats
      by ameliorating oxidative stress and mitochondrial-related apoptosis.
AB  - Early acute kidney injury (AKI) is a devastating complication in critical burn
      patients, and it is associated with severe morbidity and mortality. The mechanism
      of AKI is multifactorial. Astaxanthin (ATX) is a natural compound that is widely
      distributed in marine organisms; it is a strong antioxidant and exhibits other
      biological effects that have been well studied in various traumatic injuries and
      diseases. Hence, we attempted to explore the potential protection of ATX against
      early post burn AKI and its possible mechanisms of action. The classic severe
      burn rat model was utilized for the histological and biochemical assessments of
      the therapeutic value and mechanisms of action of ATX. Upon ATX treatment, renal
      tubular injury and the levels of serum creatinine and neutrophil gelatinase
      associated lipocalin were improved. Furthermore, relief of oxidative stress and
      tubular apoptosis in rat kidneys post burn was also observed. Additionally, ATX
      administration increased Akt and Bad phosphorylation and further down-regulated
      the expression of other downstream pro-apoptotic proteins (cytochrome c and
      caspase-3/9); these effects were reversed by the PI3K inhibitor LY294002.
      Moreover, the protective effect of ATX presents a dose-dependent enhancement. The
      data above suggested that ATX protects against early AKI following severe burns
      in rats, which was attributed to its ability to ameliorate oxidative stress and
      inhibit apoptosis by modulating the mitochondrial-apoptotic pathway, regarded as
      the Akt/Bad/Caspases signalling cascade. 

PMID- 25871291
TI  - Antifungal compounds from cyanobacteria.
AB  - Cyanobacteria are photosynthetic prokaryotes found in a range of environments.
      They are infamous for the production of toxins, as well as bioactive compounds,
      which exhibit anticancer, antimicrobial and protease inhibition activities.
      Cyanobacteria produce a broad range of antifungals belonging to structural
      classes, such as peptides, polyketides and alkaloids. Here, we tested
      cyanobacteria from a wide variety of environments for antifungal activity. The
      potent antifungal macrolide scytophycin was detected in Anabaena sp. HAN21/1,
      Anabaena cf. cylindrica PH133, Nostoc sp. HAN11/1 and Scytonema sp. HAN3/2. To
      our knowledge, this is the first description of Anabaena strains that produce
      scytophycins. We detected antifungal glycolipopeptide hassallidin production in
      Anabaena spp. BIR JV1 and HAN7/1 and in Nostoc spp. 6sf Calc and CENA 219. These
      strains were isolated from brackish and freshwater samples collected in Brazil,
      the Czech Republic and Finland. In addition, three cyanobacterial strains,
      Fischerella sp. CENA 298, Scytonema hofmanni PCC 7110 and Nostoc sp. N107.3,
      produced unidentified antifungal compounds that warrant further characterization.
      Interestingly, all of the strains shown to produce antifungal compounds in this
      study belong to Nostocales or Stigonematales cyanobacterial orders. 

PMID- 25871292
TI  - Diphlorethohydroxycarmalol inhibits interleukin-6 production by regulating NF
      kappaB, STAT5 and SOCS1 in lipopolysaccharide-stimulated RAW264.7 cells.
AB  - Diphlorethohydroxycarmalol (DPHC) is a phlorotannin compound isolated from Ishige
      okamuarae, a brown alga. This study was conducted to investigate the anti
      inflammatory effect and action mechanism of DPHC in lipopolysaccharide (LPS)
      stimulated RAW 264.7 macrophages. We found that DPHC strongly reduces the
      production of interleukin 6 (IL-6), but not that of tumor necrosis factor-alpha
      (TNF-alpha) induced by LPS. DPHC (12.5 and 100 MUM) suppressed the
      phosphorylation and the nuclear translocation of NF-kappaB (NF-kappaB), a central
      signaling molecule in the inflammation process induced by LPS. The suppressor of
      cytokine signaling 1 (SOCS1) is a negative feedback regulator of Janus kinase
      (Jak)-signal transducer and activator of transcription (STAT) signaling. In this
      study, DPHC inhibited STAT5 expression and upregulated that of SOCS1 at a
      concentration of 100 MUM. Furthermore, N-tosyl-l-phenylalanine chloromethyl
      ketone (TPCK) (a specific NF-kappaB inhibitor) and JI (a specific Jak2 inhibitor)
      reduced the production of IL-6, but not that of tumor necrosis factor-alpha (TNF
      alpha) in LPS-stimulated RAW 264.7 macrophages. These findings demonstrate that
      DPHC inhibits IL-6 production via the downregulation of NF-kappaB and Jak2-STAT5
      pathway and upregulation of SOCS1. 

PMID- 25871294
TI  - Functional recombinants designed from a fetuin/asialofetuin-specific marine algal
      lectin, rhodobindin.
AB  - Plant lectins have attracted much attention for biomedical applications including
      targeted drug delivery system and therapy against tumors and microbial
      infections. The main problem of using lectins as a biomedical tool is a batch-to
      batch variation in isoforms content. The production of lectins using
      recombination tools has the advantage of obtaining high amounts of proteins with
      more precise properties, but there are only a handful of functional recombinant
      lectins presently available. A fetuin/asialo-fetuin specific lectin, Rhodobindin,
      has unique tandem repeats structure which makes it useful in exploiting for
      recombinant lectin. We developed three functional recombinant lectins using E.
      coli expression system: one from full cDNA sequence and two from fragmentary
      sequences of Rhodobindin. Hemagglutinating activity and solubility of the
      recombinant lectins were highest at OD 0.7 cell concentration at 20  degrees C.
      The optimized process developed in this study was suitable for the quality
      controlled production of high amounts of soluble recombinant lectins. 

PMID- 25871296
TI  - Impact of phosphorus restriction and vitamin D-substitution on secondary
      hyperparathyroidism in a proteinuric mouse model.
AB  - BACKGROUND/AIMS: Since the discovery of FGF23, secondary hyperparathyroidism
      (SHPT) in renal disease has been considered to result primarily from phosphorus
      retention rather than vitamin D deficiency. However, the impact of phosphorus
      restriction and vitamin D supplementation on SHPT is still ill defined. METHODS:
      We investigated the development of SHPT in a doxorubicin-induced proteinuric
      mouse model and tested different treatment strategies including a low phosphorus
      diet and substitution with native or active vitamin D in 129 S1/SvImJ wild-type
      mice. RESULTS: Development of SHPT at day 30 was strongly related to the
      magnitude of induced proteinuria. In mice with a proteinuria <100 mg/mg
      creatinine, SHPT was mild (PTH increase 2.4-fold), and serum levels of FGF23,
      phosphate and urea remained almost stable, whereas mice with heavy proteinuria
      (>100 mg/mg creatinine) developed marked SHPT (PTH increase 10.1-fold)
      accompanied by massive increase in FGF23 (27.0-fold increase), hyperphosphatemia
      (1.8-fold increase), renal failure (7.3-fold urea increase) and depletion of both
      25-OH vitamin D and 1,25-OH vitamin D. Substitution with native or active vitamin
      D was unable to suppress SHPT, whereas a low-phosphorus diet (Pi content 0.013%)
      completely suppressed SHPT in mice with both mild and heavy proteinuria.
      CONCLUSIONS: The development of SHPT resulted from phosphate retention in this
      proteinuric model and could completely be suppressed with a low-phosphorus diet.

PMID- 25871295
TI  - Anti-obesity activity of the marine carotenoid fucoxanthin.
AB  - Nowadays the global tendency towards physical activity reduction and an augmented
      dietary intake of fats, sugars and calories is leading to a growing propagation
      of overweight, obesity and lifestyle-related diseases, such diabetes,
      hypertension, dyslipidemia and metabolic syndrome. In particular, obesity,
      characterized as a state of low-level inflammation, is a powerful determinant
      both in the development of insulin resistance and in the progression to type 2
      diabetes. A few molecular targets offer hope for anti-obesity therapeutics. One
      of the keys to success could be the induction of uncoupling protein 1 (UCP1) in
      abdominal white adipose tissue (WAT) and the regulation of cytokine secretions
      from both abdominal adipose cells and macrophage cells infiltrated into adipose
      tissue. Anti-obesity effects of fucoxanthin, a characteristic carotenoid, exactly
      belonging to xanthophylls, have been reported. Nutrigenomic studies reveal that
      fucoxanthin induces UCP1 in abdominal WAT mitochondria, leading to the oxidation
      of fatty acids and heat production in WAT. Fucoxanthin improves insulin
      resistance and decreases blood glucose levels through the regulation of cytokine
      secretions from WAT. The key structure of anti-obesity effect is suggested to be
      the carotenoid end of the polyene chromophore, which contains an allenic bond and
      two hydroxyl groups. Fucoxanthin, which can be isolated from edible brown
      seaweeds, recently displayed its many physiological functions and biological
      properties. We reviewed recent studies and this article aims to explain essential
      background of fucoxanthin, focusing on its promising potential anti-obesity
      effects. In this respect, fucoxanthin can be developed into promising marine
      drugs and nutritional products, in order to become a helpful functional food. 

PMID- 25871297
TI  - Portulaca oleracea L. as a Prospective Candidate Inhibitor of Hepatitis C Virus
      NS3 Serine Protease.
AB  - Hepatitis C virus (HCV) infection is a worldwide health problem affecting about
      300 million individuals. HCV causes chronic liver disease, liver cirrhosis,
      hepatocellular carcinoma, and death. Many side effects are associated with the
      current treatment options. Natural products that can be used as anti-HCV drugs
      are thus of considerable potential significance. NS3 serine protease (NS3-SP) is
      a target for the screening of antiviral activity against HCV. The present work
      explores plants with anti-HCV potential, isolating possible lead compounds. Ten
      plants, used for medicinal purposes against different infections in rural areas
      of Pakistan, were collected. The cellular toxicity effects of methanolic extracts
      of the plants on the viability of Huh-7 cells were studied through the Trypan
      blue dye exclusion method. Following this, the anti-HCV potential of
      phytoextracts was assessed by infecting liver cells with HCV-3a-infected serum
      inoculum. Only the methanolic extract of Portulaca oleracea L. (PO) exhibited
      more than 70% inhibition. Four fractions were obtained through bioassay-guided
      extraction of PO. Subsequent inhibition of all organic extract fractions against
      NS3 serine protease was checked to track the specific target in the virus. The
      results showed that the PO methanolic crude and ethyl acetate extract
      specifically abridged the HCV NS3 protease expression in a dose-dependent
      fashion. Hence, PO extract and its constituents either alone or with interferon
      could offer a future option to treat chronic HCV. 

PMID- 25871293
TI  - The potential of chitosan and its derivatives in prevention and treatment of age
      related diseases.
AB  - Age-related, diet-related and protein conformational diseases, such as
      atherosclerosis, diabetes mellitus, cancer, hypercholesterolemia, cardiovascular
      and neurodegenerative diseases are common in the elderly population. The
      potential of chitosan, chitooligosaccharides and their derivatives in prevention
      and treatment of age-related dysfunctions is reviewed and discussed in this
      paper. The influence of oxidative stress, low density lipoprotein oxidation,
      increase of tissue stiffness, protein conformational changes, aging-associated
      chronic inflammation and their pathobiological significance have been considered.
      The chitosan-based functional food also has been reviewed. 

PMID- 25871298
TI  - Short- but not long-term melatonin administration reduces central levels of brain
      derived neurotrophic factor in rats with inflammatory pain.
AB  - OBJECTIVE: To evaluate the effect of short- and long-term administration of
      melatonin on central brain-derived neurotrophic factor (BDNF) levels in rats with
      acute and chronic inflammatory pain. METHODS: The animals were allocated to one
      of two experiments: experiment 1 or experiment 2. In experiment 1, all animals
      were injected with complete Freund's adjuvant (CFA) to induce inflammation and
      were randomly allocated to receiving melatonin (60 mg/kg) or vehicle. Injections
      were administered 1 h after CFA and once daily for 2 more days (for a total of 3
      days of melatonin administration). In experiment 2, fifteen days after CFA
      injection, the animals were treated with melatonin (50 mg/kg) or vehicle for 8
      days. The animals were killed by decapitation 24 h after the last melatonin or
      vehicle administration, and an ELISA assay was performed to detect BDNF
      expression in the spinal cord, brainstem, and prefrontal cortex of the rats in
      both groups. Data were analyzed using Student's t test and the results are
      expressed as means +/- SEM. RESULTS: In the first experiment, the BDNF levels of
      the melatonin group were reduced in the prefrontal cortex (Student's t test, p =
      0.01) and increased in the spinal cord (Student's t test, p = 0.04). In
      experiment 2, BDNF levels were similar in both groups for all structures
      (Student's t test, p > 0.00 for all). A two-way ANOVA reveled a significant
      effect of structures (p = 0.0001) but not of treatment (p > 0.05). The prefrontal
      cortex presented higher BDNF levels than other structures (ANOVA/Student-Newman
      Keuls test, p = 0.0001). Considering the relationship between BDNF levels in all
      three structures, we found an effect of central nervous system structures (p =
      0.01) and an interaction between treatment and structures (p = 0.04). CONCLUSION:
      The high spinal cord BDNF levels and the low prefrontal cortical BDNF levels
      observed in rats with acute CFA-induced inflammation following short-term
      melatonin administration may be related to the pain-modulating and
      neuroprotective effects of this protein. Long-term melatonin administration did
      not alter BDNF levels in chronic inflammation.

PMID- 25871299
TI  - Bilateral renal dysplasia, nephroblastomatosis, and bronchial stenosis. A new
      syndrome?
AB  - Bilateral nephroblastomatosis (NB) is an uncommon renal anomaly characterized by
      multiple confluent nephrogenic rests scattered through both kidneys, with only a
      limited number of cases reported in the medical literature. Some of these
      children may have associated either Perlman or Beckwith-Wiedemann syndrome and
      others do not demonstrate syndromic features. We report a full-term boy with
      anteverted nose, bilateral bronchial stenosis due to lack of cartilage, bilateral
      obstructive renal dysplasia and NB with glomeruloid features. The infant had
      visceromegaly, but neither gigantism nor hemihypertrophy. Immunohistochemistry
      for PAX2 (Paired box gene-2) and WT-1 (Wilms Tumor 1) were strongly positive in
      the areas of NB. GLEPP-1 (Glomerular Epithelial Protein) did not stain the areas
      of NB with a glomeruloid appearance, but was positive in the renal glomeruli as
      expected. We found neither associated bronchial stenosis nor the histology of NB
      resembling giant glomeruli in any of the reported cases of NB. 

PMID- 25871300
TI  - "Signal-on" photoelectrochemical biosensor for sensitive detection of human T
      Cell lymphotropic virus type II DNA: dual signal amplification strategy
      integrating enzymatic amplification with terminal deoxynucleotidyl transferase
      mediated extension.
AB  - A novel "signal-on" photoelectrochemical (PEC) biosensor for sensitive detection
      of human T-cell lymphotropic virus type II (HTLV-II) DNA was developed on the
      basis of enzymatic amplification coupled with terminal deoxynucleotidyl
      transferase (TdT)-mediated extension strategy. The intensity of the photocurrent
      signal was proportional to the concentration of the HTLV-II DNA-target DNA (tDNA)
      by dual signal amplification. In this protocol, GR-CdS:Mn/ZnS nanocomposites were
      used as photoelectric conversion material, while pDNA was used as the tDNA
      recognizing unit. Moreover, the TdT-mediated extension and the enzymatic signal
      amplification technique were used to enhance the sensitivity of detection. Using
      this novel dual signal amplification strategy, the prototype of PEC DNA sensor
      can detect as low as ~0.033 fM of HTLV-II DNA with a linear range of 0.1-5000 fM,
      with excellent differentiation ability even for single-base mismatches. This PEC
      DNA assay opens a promising platform to detect various DNA targets at ultralow
      levels for early diagnoses of different diseases. 

PMID- 25871301
TI  - Determination of the Rate Constants for the NH2(X(2)B1) + NH2(X(2)B1) and
      NH2(X(2)B1) + H Recombination Reactions in N2 as a Function of Temperature and
      Pressure.
AB  - The recombination rate constants for the reactions NH2 + NH2 -> N2H4 (reaction
      k1b) and NH2 + H -> NH3 (reaction k2b) with N2 as a third-body have been measured
      as a function of temperature and pressure. The temperature range was from 292 to
      533 K and the pressure range from a few Torr up to 300-400 Torr, well within the
      pressure falloff region. The NH2 radical was produced by 193 nm pulsed-laser
      photolysis of NH3 in a temperature controlled flow chamber. High-resolution time
      resolved laser absorption spectroscopy was used to follow the temporal
      concentration profiles of both NH2 and NH3, simultaneously. The NH2 radical was
      monitored at 14800.65 cm(-1) using the (1)231 (0,7,0)A(2)A1 <- (1)331
      (0,0,0)X(2)B1 ro-vibronic transition, and NH3 monitored at 3336.39 cm(-1) on the
      (q)Q3(3)s (1,0,0,0) <- (0,0,0,0) ro-vibrational transition. The necessary
      collisional broadening parameters for each molecule were measured in separate
      experiments. The pressure and temperature dependence of k1b can be represented by
      the Troe parameters: k0, the low-pressure three-body recombination rate constant,
      k0(T) = (1.14 +/- 0.59) * 10(-19)T(-(3.41+/-0.28)) cm(6) molecule(-2) s(-1), and
      Fcent, the pressure broadening parameter, Fcent = 0.15 +/- 0.12, independent of
      temperature. The data could not be fit by three-independent parameters, and the
      high-pressure limiting rate constant kinfinity(T) = 9.33 * 10(-10)T(-0.414)
      e(33/T) cm(3) molecule(-1) s(-1) was taken from the high-quality theoretical
      calculations of Klippenstein et al. (J. Phys. Chem A 2009, 113, 10241). The
      pressure and temperature dependence of k2b, can be represented by the Troe
      parameters: k0(T) = (9.95 +/- 0.58) * 10(-26)T((-1.76+/-0.092)) cm(6) molecule(
      2) s(-1), Fcent = 0.5 +/- 0.2, kinfinity = 2.6 * 10(-10) cm(3) molecule(-1) s(
      1). Again, the data could not be fit with three independent parameters, and
      k2binfinity was chosen to be 2.6 * 10(-10) cm(3) molecule(-1) s(-1) and fixed in
      the analysis. 

PMID- 25871302
TI  - Palladium-Catalyzed C(sp(3))-C(sp(2)) Cross-Coupling of
      (Trimethylsilyl)methyllithium with (Hetero)Aryl Halides.
AB  - The palladium-catalyzed direct cross-coupling of a range of organic chlorides and
      bromides with the bifunctional C(sp(3))-(trimethylsilyl)methyllithium reagent is
      reported. The use of Pd-PEPPSI-IPent as the catalyst allows for the preparation
      of structurally diverse and synthetically versatile benzyl- and allylsilanes in
      high yields under mild conditions (room temperature) with short reaction times. 

PMID- 25871303
TI  - Updated clinical practice guidelines for concussion/mild traumatic brain injury
      and persistent symptoms.
AB  - OBJECTIVE: To introduce a set of revised guidelines for the management of mild
      traumatic brain injury (mTBI) and persistent symptoms following concussive
      injuries. QUALITY OF EVIDENCE: The Guidelines for Mild Traumatic Brain Injury and
      Persistent Symptoms were made available in March 2011 based on literature and
      information up to 2008. A search for new clinical practice guidelines addressing
      mTBI and a systematic review of the literature evaluating treatment of persistent
      symptoms was conducted. Healthcare professionals representing a range of
      disciplines from Canada and abroad attended a consensus conference to revise the
      original guidelines in light of new evidence. MAIN MESSAGE: A modified Delphi
      process was used to create 96 recommendations addressing the diagnosis and
      management of mTBI and persistent symptoms, including post-traumatic headache,
      sleep disturbances, mental health disorders, cognitive difficulties, vestibular
      and vision dysfunction, fatigue and return to activity/work/school. Numerous
      resources, tools and treatment algorithms were also included to aid
      implementation of the recommendations. CONCLUSION: The revised clinical practice
      guideline reflects the most current evidence and is recommended for use by
      clinicians who provide care to people who experience PPCS following mTBI.

PMID- 25871304
TI  - Incident cancer in a cohort of 3,247 cancer diagnosis free ischemic stroke
      patients.
AB  - BACKGROUND: Subclinical cancer can manifest as a thromboembolic event and may be
      detected at a later interval in ischemic stroke survivors. We determined the rate
      of incident cancer and effect on cardiovascular endpoints in a large cohort of
      ischemic stroke survivors. METHODS: An analysis of 3,680 adults with nondisabling
      cerebral infarction who were followed for two years within the randomized, double
      blinded VISP trial was performed. The primary intervention was best
      medical/surgical management plus a daily supplementation of vitamin B6, vitamin
      B12, and folic acid. We calculated age-adjusted rates of incidence of cancer
      among ischemic stroke survivors and standardized incidence ratios (SIR) with 95%
      confidence intervals (CI) based on comparison with age-adjusted rates in the
      general population. The significant variables from univariate analysis were
      entered in a Cox Proportional Hazards analysis to identify the association
      between various baseline factors and incident cancer after adjusting age, gender,
      and race/ethnicity. A logistic regression analysis evaluated the association
      between incident cancer and various endpoints including stroke, coronary heart
      disease, myocardial infarction, and death after adjusting age, gender, and
      race/ethnicity. RESULTS: A total of 3,247 patients (mean age +/- SD of 66 +/- 11;
      2,013 were men) were cancer free at the time of enrollment. The incidence of new
      cancer was 0.15, 0.80, 1.2, and 2.0 per 100 patients at 1 month, 6 months, 1
      year, and 2 years, respectively. The age-adjusted annual rate of cancer in
      patients with ischemic stroke was higher than in persons in the general
      population at 1 year (581.8/100,000 persons vs. 486.5/100,000 persons, SIR 1.2,
      95% CI 1.16-1.24) and 2 years (1,301.7/100,000 vs. 911.5/100,000, SIR 1.4, 95% CI
      1.2-1.6) after recruitment. There was a higher risk for death (odds ratio (OR)
      3.1, 95% CI 1.8-5.4), and composite endpoint of stroke, coronary heart disease,
      and/or death (OR 1.4, 95% CI 1.0-2.2) among participants who developed incident
      cancer compared with those who were cancer free after adjusting for potential
      confounders. CONCLUSIONS: The annual rate of age-adjusted cancer incidence was
      higher among ischemic stroke patients compared with those in the general
      population. The odds of mortality were three folds higher among stroke survivors
      who developed incident cancer.

PMID- 25871305
TI  - Barriers and facilitators to antiretroviral therapy adherence among patients with
      HIV in Bissau, Guinea-Bissau: A qualitative study.
AB  - Adherence is a decisive factor in achieving a successful response to
      antiretroviral therapy (ART) for HIV infection. No previous studies have been
      conducted regarding HIV treatment adherence in Guinea-Bissau. In this study we
      assessed barriers and facilitators to patient ART adherence. Semi-structured
      interviews were conducted with 20 adult, HIV infected individuals receiving ART
      at a HIV treatment centre in Bissau, Guinea-Bissau. The grounded theory method
      was used to gather and analyse data. Results indicated that HIV-related knowledge
      was a determining factor for optimal adherence. The facilitators were experienced
      treatment benefits and complementing social networks. The barriers were treatment
      related costs and competing livelihood needs; poor clinic infrastructure;
      perceived stigma; and traditional practices. Our findings indicate that good ART
      adherence, especially in resource-limited settings, requires that patients
      achieve adequate HIV-related knowledge. More studies on HIV-related knowledge and
      adherence among HIV infected individuals are currently needed. 

PMID- 25871306
TI  - Demographic and health surveys indicate limited impact of condoms and HIV testing
      in four African countries.
AB  - Condom promotion and HIV testing for the general population have been major
      components of HIV prevention efforts in sub-Saharan Africa's high prevalence HIV
      epidemics, although little evidence documents their public health impact. Recent
      enhancements to the large, population-based demographic and health surveys (DHS)
      and AIDS information surveys (AIS) allow use of these data to assess the
      population-wide impact of these strategies. We analysed the latest DHS and AIS
      data from four sub-Saharan African countries with high prevalence, heterosexually
      transmitted HIV epidemics (Cote d'Ivoire, Swaziland, Tanzania and Zambia; N = 48
      298) to answer two questions: 1) Are men and women who use condoms less likely to
      be HIV-infected than those who do not?; and 2) Are men and women who report
      knowing their HIV status more likely to use condoms than those who do not?
      Consistent condom use was associated with lower HIV infection rates for Swazi men
      but with higher HIV infection rates for women in Tanzania and Zambia; it made no
      significant difference in the other five sex/country subgroups analysed.
      Inconsistent condom use was not significantly associated with HIV status in any
      subgroup. Knowing one's HIV status was consistently associated with higher rates
      of condom use only among married people who were HIV-positive, even though condom
      use in this group remained relatively low. Effects of knowing one's HIV status
      among other subgroups varied. These results suggest that condoms have had little
      population-wide impact for HIV/AIDS prevention in these four countries. HIV
      testing appears to be associated with increased condom use mainly among people in
      stable partnerships who test positive. HIV testing and condom promotion may be
      more effective when targeted to specific groups where there is evidence of
      benefit rather than to general populations. 

PMID- 25871307
TI  - Patents and profits: A disparity of manufacturing margins in the tenofovir value
      chain.
AB  - Registered in 2001, tenofovir disoproxil fumarate (TDF) has quickly become a
      mainstay of first line regimens for the treatment of HIV. Initially only
      available in developed countries at a cost of US$5 000 per person per year (ppy),
      Gilead's Access Programme (GAP) has extended the use of the product to 2.4
      million patients in low and middle income countries. The programme has two
      components: distribution of the branded product at reduced prices and licensing
      partnerships with generic manufacturers. The licensing partnerships now supply
      75% of the market by volume, at a treatment cost of US$57 ppy (1% of the branded
      cost). From Gilead's perspective, GAP must be considered a huge success. It has
      enabled the company to maintain high prices in developed countries whilst
      reducing its input costs and deflecting criticism of its failure to provide
      essential medicines for the poor, hence risking the possibility of compulsory
      licensing. Over the period 2001 to 2011, TDF in its various forms has generated
      for Gilead more than US$31 billion revenue at a gross margin of 80%, equivalent
      to a gross profit of US$25 billion. Analysis of the TDF value chain, from
      preparation of the active pharmaceutical ingredient (API) to sale of the
      formulated product, shows that manufacturing margins are highly skewed in favour
      of the originator, with the latter's profit being US$3.2 billion vs. US$4 million
      for API manufacturers and US$39 million for formulators (2011). The data argues
      for a more rational approach to drug pricing including possible regulation in
      developed countries and more sustainable margins for the generic producers. 

PMID- 25871308
TI  - Gender, relationship dynamics and South African girls' vulnerability to sexual
      risk.
AB  - South African researchers have stressed the importance of gender and relationship
      dynamics underlying sexual risk, particularly among 15- to 19-year-olds.
      Nevertheless, we know little about these factors among young girls, who are
      especially at risk of HIV. The main objective in this study was to explore the
      ways that young girls aged 16 to 17 years give meaning to boys and boyfriends and
      the processes through which these relationship dynamics are shaped. In-depth
      interviews were conducted with a group of black girls in a working class context
      in Durban about their sexual relationships with boys. Dominant gender norms
      underlined the ways in which girls discussed these sexual relationships in
      relation to their lack of power and condom use. Factors such as their class, race
      and gender interacted with girls' vulnerability to risk of HIV. While girls were
      complicit in their subordination, particularly in relation to cheating
      boyfriends, many were critical of boys who displayed patterns of sexual
      domination. Efforts aimed at reducing sexual risk must work toward shifting
      dominant patterns of masculinity over femininity to broaden pathways of love,
      trust, loyalty and understanding. 

PMID- 25871309
TI  - Professional nurses' views regarding stigma and discrimination in the care of HIV
      and AIDS patients in rural hospitals of the Limpopo province, South Africa.
AB  - The aim of the study was to determine the views of professional nurses on the
      manifestations of HIV and AIDS stigma and discrimination and their influence on
      the quality of care rendered to people living with HIV and AIDS in three rural
      hospitals of Limpopo province, South Africa. The study was qualitative,
      exploratory, descriptive and contextual in nature. The population included all
      professional nurses registered with the South African Nursing Council who were
      working with confirmed HIV-positive patients in the three hospitals and had
      received specialised training in voluntary counselling and testing (VCT),
      antiretrovirals (ARV), prevention of mother-to-child transmission (PMTCT) and
      couple counselling. A purposive sampling method was used to select both the wards
      and participants, based on set criteria. A total of 9 wards (6 adult medical and
      3 maternity) and 37 participants were selected. Focus group discussions and semi
      structured and key informant interviews were conducted. Data were analysed using
      a combination of data analysis guidelines from different sources. Results
      revealed that professional nurses were aware of the existence of HIV and AIDS
      stigma and discrimination in their wards and regarded these as bad and improper
      care of HIV-positive patients. Behaviour included leaving care of HIV patients to
      junior members of staff with limited skills and knowledge of HIV and AIDS;
      showing HIV-positive patients that their disease was dangerous and contagious;
      judgmental behaviour towards and stereotyping of HIV-positive patients; and
      regarding patients with HIV and AIDS as uncooperative and problematic in the
      wards. 

PMID- 25871310
TI  - Self-testing as strategy to increase the uptake of HIV testing in South Africa.
AB  - With better health care and greater access to antiretrovirals (ARVs) it has
      become important to increase the uptake of HIV testing. Major testing campaigns
      have been launched in South Africa, but no official provision exists for clients
      who prefer self-testing for HIV. The purpose of this study was to investigate
      which HIV-testing model (client-initiated, provider-initiated or self-testing) a
      sample of South Africans preferred and why. A semi-structured questionnaire was
      completed by 466 participants and 9 provinces were represented by the sample. The
      results indicated that 22.3% of the participants preferred self-testing for HIV
      (while 66.1% preferred client-initiated and 11.6% provider-initiated counselling
      and testing). Participants who preferred self-testing for HIV were predominantly
      (p < 0.05) male, white, lived in cities or towns, did not know their HIV status,
      and had no intention of being tested at a medical facility in future. The
      underlying themes of why participants preferred self-testing for HIV above
      testing in a medical facility were the need for privacy and confidentiality; the
      need to keep testing as well as the results secret; fear of discrimination and
      stigma; distrust in the health care system to keep results confidential; and an
      aversion to face-to-face counselling. Participants indicated that they would
      consider testing if self-testing for HIV with telephone counselling becomes
      readily available in their communities. HIV testing models in South Africa should
      be revisited and revised to offer people who would otherwise not be tested, with
      an alternative method of testing. 

PMID- 25871311
TI  - Governing AIDS through aid to civil society: Global solutions meet local problems
      in Mozambique.
AB  - The aim of this article is to explore how international donors influence civil
      society organisations (CSOs) in Mozambique through funding mechanisms, the
      creation of partnerships, or inclusion in targeted programmes. The main focus is
      the relationship between donors and AIDS non-governmental organisations (NGOs).
      The main questions the paper aims to answer are: Who is setting the agenda? What
      power mechanisms are in place to fulfil planned projects and programmes? Are
      there any forms of resistance from civil society AIDS-organisations in the face
      of the donor interventions? The actions will be analysed through the lens of
      governmentality theory. The study concluded that donors have the power to set the
      agenda through predetermined programmes and using various technologies. Their
      strongest weapons are audit mechanisms such as the result based management model
      used as a control mechanism, and there is still a long way to go to achieve a
      situation with multiple forms of local resistance to the conditions set by
      economically powerful donors. The standardisation imposed through clustering
      donors into like-minded groups and other constellations gives them power to
      govern the politics of AIDS. 

PMID- 25871312
TI  - Modelling the potential impact and cost of scaling-up male circumcision in
      resource poor settings: A case of Uganda.
AB  - This study modelled estimates of the cost and impact of male circumcision (MC)
      under different scenarios using the Decision Maker's Program Planning Tool on
      data from Uganda. Results showed that the number of new adult HIV infections
      could be reduced by 23 000 if MC could be increased from the current 25% to 80%
      by 2015. The incidence of HIV could be reduced by 0.2 percentage points over the
      same period. If a scale up programme is to meet a target of 80% by 2015 then the
      annual number of MCs performed should be over twice as many as those performed in
      2011. The discounted net cost per infection averted would be US$559 for the
      period 2011-2015 and the country would save US$6 841 per infection. A scale up of
      MC will reduce HIV prevalence and incidence substantially and it would be highly
      cost effective. The government should mobilise funding to meet high MC targets
      that would deliver the desired reduction in prevalence and incidence in a short
      period of time. 

PMID- 25871313
TI  - Red Bean Extract Inhibits Lipopolysaccharide-Induced Inflammation and H2O2
      Induced Oxidative Stress in RAW 264.7 Macrophages.
AB  - Red bean (Phaseolus radiatus L. var. Aurea) is a leguminous seed and mainly used
      as one of the popular ingredients in oriental desserts. The objective of this
      study was to evaluate the anti-inflammatory activity of 50 g/kg ethanolic extract
      of red bean (RBE) by measuring lipopolysaccharide (LPS)-induced expressions of
      nitric oxide (NO), inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX
      2), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) in RAW
      264.7 macrophages. On the other hand, the antioxidant activity of RBE was
      determined by thiobarbituric acid reactive substances method and comet assay
      using H2O2-induced macrophages. The results showed that RBE at the concentrations
      of 50-200 MUg/mL can significantly suppress the inflammatory responses in LPS
      stimulated macrophages through the reduction of cellular NO and downregulation of
      the gene expressions of iNOS, COX-2, TNF-alpha, and IL-6 in a dose-dependent
      manner. Furthermore, RBE can diminish H2O2-induced oxidative damage in RAW 264.7
      macrophage. Phenolic compounds and cyanidin-3-O-glucoside from BRE may have
      efficacy as overall in vitro anti-inflammatory and antioxidant agents. Red bean
      exerts an anti-inflammatory response and has potential as a health-promoting
      ingredient. 

PMID- 25871314
TI  - Association of psychological distress late in life and dementia-related
      mortality.
AB  - OBJECTIVE: It is not fully understood how subjective feelings of psychological
      distress prognosticate dementia. Our aim was to investigate the association
      between self-reported psychological distress and risk of dementia-related
      mortality. METHOD: We included 31,043 eligible individuals between the ages of 60
      and 80 years, at time of examination, from the CONOR (Cohort of Norway) database.
      They were followed for a period of 17.4 years (mean 11.5 years). The CONOR Mental
      Health Index, a seven-item self-report scale was used. A cut-off score equal to
      or above 2.15 on the scale denoted psychological distress. Cox regression was
      used to assess the association between psychological distress and risk of
      dementia-related mortality. RESULTS: Total number of registered deaths was 11,762
      and 1118 (9.5%) were classified as cases of dementia-related mortality. We found
      that 2501 individuals (8.1%) had psychological distress, of these, 119 (10.6%)
      had concomitant dementia-related mortality. Individuals with psychological
      distress had an increased risk of dementia-related mortality HR = 1.52 (95%
      confidence interval (CI) 1.25-1.85) after adjusting for age, gender and
      education. The association remained significant although attenuated when
      implemented in a full adjusted model, including general health status, smoking,
      obesity, hypertension, diabetes and history of cardiovascular disease; hazard
      ratio, HR = 1.30 (95% CI 1.06-1.59). CONCLUSION: Our results indicate that
      psychological distress in elderly individuals is associated with increased risk
      of dementia-related mortality. Individuals at increased risk of dementia may
      benefit from treatments or interventions that lessen psychological distress, but
      this needs to be confirmed in future clinical studies.

PMID- 25871315
TI  - The effectiveness of preoperative trimetazidine on myocardial preservation in
      coronary artery bypass graft patients: a systematic review and meta-analysis.
AB  - BACKGROUND: Coronary artery bypass grafting (CABG) is a key and effective
      surgical treatment modality for coronary artery disease. Unfortunately, ischemia
      reperfusion injury during and after CABG can lead to reversible and irreversible
      myocardial damage. Trimetazidine [1-(2,3,4-trimethoxybenzyl)piperazine
      dihydrochloride] is a metabolic anti-ischemic agent with demonstrated
      cardioprotective effects; however, its effects with respect to myocardial
      preservation in CABG patients remain unclear. METHODS: We conducted a systematic
      review and meta-analysis of randomized controlled trials (RCTs) to investigate
      the effectiveness of myocardial preservation of preoperative trimetazidine
      therapy in CABG patients by assessing the postoperative levels of several blood
      based biochemical markers of myocardial injury, including creatine kinase (CK),
      creatine kinase-muscle and brain (CK-MB), creatine phosphokinase (CPK), troponin
      T (TnT) and troponin I (TnI). The RCTs were classified into two subgroup analyses
      by the timing of sample collection (either <=12 or >12 h after CABG). RESULTS:
      Six RCTs were finally included in the meta-analysis. The pooled effect sizes
      showed significantly lower postoperative levels of CK, CK-MB, TnT and TnI in the
      trimetazidine-treated CABG patients relative to control CABG patients. However,
      there were no significant differences in the postoperative CPK levels between
      trimetazidine-treated CABG patients relative to control CABG patients. In both
      the <=12 and >12 h post-CABG subgroup analyses, significant differences in CK, CK
      MB, TnT and TnI were detected between the trimetazidine-treated CABG patients
      relative to control CABG patients. CONCLUSIONS: Preoperative trimetazidine
      therapy appears to have a positive effect on myocardial preservation in CABG
      patients.

PMID- 25871316
TI  - Pancreatic Fistulae after Urologic Surgery - A Single Centre Experience.
AB  - INTRODUCTION: To evaluate incidence, symptoms and management of postoperative
      pancreatic fistula (POPF) after urologic surgery based on our experience.
      MATERIAL AND METHODS: Database was searched for clinically evident POPF after
      urologic surgery between 1998 and 2014. Fistulae were graded using the POPF
      classification. Clinical course of every POPF patient was evaluated. RESULTS:
      During this time, 3,200 surgeries for renal, adrenal and retroperitoneal
      pathologies were performed. Twelve POPF occurred postoperatively in this series.
      Eight fistulae were POPF grade A, 3 POPF grade B and one POPF grade C. POPF
      became clinically evident after a median of 3 days (IQR 2-3). In all POPF grade
      A/B patients, secretion from the pancreatic fistula completely subsided under
      conservative therapy. In one POPF grade C patient with positive surgical margins
      of urothelial cancer, conservative treatment failed and the patient died due to
      POPF-related sepsis. CONCLUSIONS: POPF is a rare complication after urologic
      surgery. Conservative therapy is the first choice of treatment and will be
      successful in the majority of cases. Pancreatic fistula after surgery of
      recurrent malignancy may have a poor outcome.

PMID- 25871317
TI  - Biomimetic topography and chemistry control cell attachment to amyloid fibrils.
AB  - Networks of nanoscale fibrous coatings made from self-assembled peptides are
      promising candidates for biomaterials that can promote the growth of mammalian
      cells. One particularly attractive feature is the possibility of adding
      biofunctional sequences to peptides to promote cell attachment. We deconvolute
      the topographic and chemical effects of nanoscale fibrils on cells by depositing
      a plasma polymer film on TTR1-based fibrils decorated with a range of cell
      adhesive chemistries (RGD and cycloRGDfK), producing a surface that retains the
      nanoscale fibrous topography of surface-bound fibrils but lacks the fibril
      surface chemistry. The surface topography was found to influence cell toxicity
      and spreading, and the fibril surface chemistry influenced cell attachment and
      spreading. This study highlights the importance of considering both the chemical
      and physical features of novel biomaterials and illustrates the use of plasma
      polymer deposition as a tool for examining the relationship between amyloid
      fibril structure and function. 

PMID- 25871319
TI  - PFI-14(c): A Rasch Analysis Refinement of the Psoriasis Family Index.
AB  - OBJECTIVE: We aimed to assess the psychometric properties of the Psoriasis Family
      Index (PFI), a disease-specific instrument, to measure the secondary impact of
      psoriasis on the quality of life (QoL) of family members and partners of
      psoriasis patients. METHODS: PFI data were collected from 150 accompanying family
      members of psoriasis patients attending the dermatology department of a secondary
      referral hospital. Rasch analysis was used to examine various psychometric
      properties of the PFI, including dimensionality, response category functioning,
      fit statistics, scale reliability and validity, item targeting and differential
      item functioning (DIF). RESULTS: The 15-item PFI with 4 response options showed
      good overall fit to the Rasch model. The response category almost entirely
      followed the Linacre criteria, demonstrating its optimal functionality. All items
      except one had good fit to the Rasch model. The mean fit residual for the items
      was -0.085 +/- 1.184 (range -1.54 to 2.7). Strict unidimensionality was achieved
      following removal of the misfitting item 5. The revised 14-item PFI maintained
      strong reliability (person separation index = 0.87). The scale showed minor
      mistargeting (mean difference between person and item location = 0.95 logits).
      None of the items displayed DIF across gender or relationship type. CONCLUSIONS:
      The PFI is the first disease-specific measure to quantify the QoL of family
      members of psoriasis patients. Following the application of Rasch analysis we now
      recommend the use of a 14-item version of the PFI: question No. 5 from the 15
      item version has been deleted. This study demonstrates the promising psychometric
      performance of the PFI and confirms its potential as a useful outcome measure in
      future clinical research.

PMID- 25871320
TI  - Salivary Testosterone Is Consistently and Positively Associated with
      Extraversion: Results from The Netherlands Study of Depression and Anxiety.
AB  - BACKGROUND: Testosterone has been postulated as a 'social' hormone, but the
      relationship between testosterone and personality traits linked with socially
      oriented behaviors such as extraversion remains unclear. The objective of our
      study was to investigate the association between baseline salivary testosterone
      levels and the Big Five personality traits. METHODS: We studied the relationship
      between salivary testosterone (morning and evening) and NEO-FFI (Five-Factor
      Inventory) personality traits in 1,611 participants with lifetime or current
      depression and/or anxiety and 482 participants without depression/anxiety of the
      Netherlands Study of Depression and Anxiety (NESDA). RESULTS: The personality
      domain of extraversion was independently associated with higher salivary
      testosterone, both in healthy subjects (beta = 0.094; p = 0.04) and in subjects
      with lifetime or current depression and/or anxiety (beta = 0.092; p < 0.001). In
      multivariable adjusted analyses, extraversion remained the only personality trait
      that was positively associated with salivary testosterone (beta = 0.079; p =
      0.006). CONCLUSION: We conclude that salivary testosterone is consistently and
      positively related to extraversion, supporting the notion of a hormonal basis of
      this personality trait, which may be linked to the tendency to strive for and
      maintain social status. (c) 2015 S. Karger AG, Basel.

PMID- 25871318
TI  - Methamphetamine blunts Ca(2+) currents and excitatory synaptic transmission
      through D1/5 receptor-mediated mechanisms in the mouse medial prefrontal cortex.
AB  - Psychostimulant addiction is associated with dysfunctions in frontal cortex.
      Previous data demonstrated that repeated exposure to methamphetamine (METH) can
      alter prefrontal cortex (PFC)-dependent functions. Here, we show that withdrawal
      from repetitive non-contingent METH administration (7 days, 1 mg/kg) depressed
      voltage-dependent calcium currents (ICa ) and increased hyperpolarization
      activated cation current (IH ) amplitude and the paired-pulse ratio of evoked
      excitatory postsynaptic currents (EPSCs) in deep-layer pyramidal mPFC neurons.
      Most of these effects were blocked by systemic co-administration of the D1/D5
      receptor antagonist SCH23390 (0.5 and 0.05 mg/kg). In vitro METH (i.e. bath
      applied to slices from naive-treated animals) was able to emulate its systemic
      effects on ICa and evoked EPSCs paired-pulse ratio. We also provide evidence of
      altered mRNA expression of (1) voltage-gated calcium channels P/Q-type Cacna1a
      (Cav 2.1), N-type Cacna1b (Cav 2.2), T-type Cav 3.1 Cacna1g, Cav 3.2 Cacna1h, Cav
      3.3 Cacna1i and the auxiliary subunit Cacna2d1 (alpha2delta1); (2)
      hyperpolarization-activated cyclic nucleotide-gated channels Hcn1 and Hcn2; and
      (3) glutamate receptors subunits AMPA-type Gria1, NMDA-type Grin1 and
      metabotropic Grm1 in the mouse mPFC after repeated METH treatment. Moreover, we
      show that some of these changes in mRNA expression were sensitive D1/5 receptor
      blockade. Altogether, these altered mechanisms affecting synaptic physiology and
      transcriptional regulation may underlie PFC functional alterations that could
      lead to PFC impairments observed in METH-addicted individuals. 

PMID- 25871321
TI  - Imatinib Mesylate Dose Adjustment Based on Body Surface Area for CML Chronic
      Phase Patients Intolerant to Standard Dosage.
AB  - AIM: Chronic myelogenous leukemia (CML) chronic phase (CP) patients cannot
      tolerate a standard dose (400 mg/day) of imatinib mesylate (IM), sometimes
      needing a reduced dose. This study aimed to find convenient clinical indexes,
      rather than plasma trough levels of IM, to define the appropriate IM dosage.
      METHODS: Seventy CML CP patients who experienced an IM dose reduction, or a
      temporary cessation, were enrolled from 2002 to 2010. The IM treatment was
      resumed and maintained at either >=400 mg in 25 patients (35.7%; group >=400 mg)
      or at <=300 mg in 45 patients (64.3%; group <=300 mg). The various clinical
      characteristics of these patients were evaluated. The plasma trough level of IM
      was monitored in 20 patients from group <=300 mg. RESULTS: Via multivariate
      analysis, the IM dosage divided by the body surface area (BSA) was an important
      index, presupposing a complete cytogenetic response at 12 months (CCyR12).
      Patients with IM/BSA >206.7 mg/m2 showed a higher probability of CCyR12 than
      others. The IM/BSA (221.7 mg/m2) in group <=300 mg was higher than in group >=400
      mg (207.6 mg/m2). The sustained response and survival rate of group <=300 mg was
      comparable to that of group >=400 mg. The plasma trough level of IM was
      significantly correlated with the IM/BSA. CONCLUSION: Our study suggests that IM
      dose adjustments, based on IM/BSA, could improve the clinical outcomes in CML CP
      patients.

PMID- 25871322
TI  - The Value of Rectal Cultures in Treatment of Sepsis Following Post-Transrectal
      Ultrasound-Guided Prostate Biopsy.
AB  - BACKGROUND: Cases with sepsis after transrectal ultrasound-guided prostate biopsy
      (TRUSPB) were documented, with special focus on cultures and susceptibility of
      isolates. We also evaluated the contribution of concomitant rectal cultures to
      the treatment of selective cases. MATERIALS AND METHODS: Patients with sepsis
      after TRUSPB were followed prospectively. Manifestations and risk factors for
      antimicrobial resistance were documented. Results of urine and blood cultures and
      antimicrobial susceptibility were recorded for all participating patients. In 40
      patients, rectal swab cultures were obtained concomitantly. RESULTS: Ninety-five
      patients were consecutively studied. Sepsis symptoms started showing up within 48
      h after biopsy in 93% of patients. At least one of the cultures was positive in
      72 patients. E. coli grew in 70 cases; isolates were highly resistant: 67%
      displayed multidrug-resistance. Rectal cultures grew E. coli in 38 cases. In
      patients with positive E. coli in rectum and in at least one additional culture
      (blood and/or urine), the antibiogram was identical in all cases but one. Eight
      cases had negative cultures. CONCLUSION: The prevalence of antimicrobial
      resistance among E. coli isolates from patients with TRUSPB sepsis was alarming.
      Susceptibilities of rectal E. coli isolates used for deescalation of initial
      empiric treatment in culture-negative TRUSPB sepsis can contribute to the
      reduction of broad-spectrum antibiotics exposure.

PMID- 25871323
TI  - Dysfunctional Dopaminergic Neurones in Mouse Models of Huntington's Disease: A
      Role for SK3 Channels.
AB  - BACKGROUND: Huntington's disease (HD) is a late-onset fatal neurodegenerative
      disorder caused by a CAG trinucleotide repeat expansion in the gene coding for
      the protein huntingtin and is characterised by progressive motor, psychiatric and
      cognitive decline. We previously demonstrated that normal synaptic function in HD
      could be restored by application of dopamine receptor agonists, suggesting that
      changes in the release or bioavailability of dopamine may be a contributing
      factor to the disease process. OBJECTIVE: In the present study, we examined the
      properties of midbrain dopaminergic neurones and dopamine release in
      presymptomatic and symptomatic transgenic HD mice. METHODS AND RESULTS: Using
      intracellular sharp recordings and immunohistochemistry, we found that neuronal
      excitability was increased due to a loss of slow afterhyperpolarisation and that
      these changes were related to an apparent functional loss and abnormal
      distribution of SK3 channels (KCa2.3 encoded by the KCNN3 gene), a class of small
      conductance calcium-activated potassium channels. Electrochemical detection of
      dopamine showed that this observation was associated with an enhanced dopamine
      release in presymptomatic transgenic mice and a drastic reduction in symptomatic
      animals. These changes occurred in the context of a progressive expansion in the
      CAG repeat number and nuclear localisation of mutant protein within the
      substantia nigra pars compacta. CONCLUSIONS: Dopaminergic neuronal dysfunction is
      a key early event in HD disease progression. The initial increase in dopamine
      release appears to be related to a loss of SK3 channel function, a protein
      containing a polyglutamine tract. Implications for polyglutamine-mediated
      sequestration of SK3 channels, dopamine-associated DNA damage and CAG expansion
      are discussed in the context of HD.

PMID- 25871324
TI  - The pyridone-annelated isoindigo (5'-Cl) induces apoptosis, dysregulation of
      mitochondria and formation of ROS in leukemic HL-60 cells.
AB  - BACKGROUND/AIMS: In our quest to develop an isoindigo with improved efficacy and
      bioavailability, we recently synthesized a series of novel substituted pyridone
      annelated isoindigo and evaluated their antiproliferative effects. We identified
      the compound [(E)-1-(5'-Chloro-2'-oxoindolin-3'-ylidene)-6-ethyl-2,3,6,9
      tetrahydro-2,9-dioxo-1H-pyrrolo[3,2-f] quinoline-8-carboxylic acid], abbreviated
      as 5'-Cl, which shows selective antiproliferative activities against various
      cancer cell lines mediated through apoptosis. Here we have investigated the
      molecular mechanisms underlying the apoptotic activity of 5'-Cl in the human
      promyelocytic leukemia HL-60 cells. METHODS: We employed different methods to
      determine the apoptotic pathways triggered by 5'-Cl in HL-60 cells, using flow
      cytometry, nuclear staining, caspases activation, mitochondria functioning,
      generation of reactive oxygen species (ROS) and Western blotting techniques.
      RESULTS: Low concentrations (1-8 uM) of 5'-Cl inhibited the growth of HL-60 cells
      in a dose and time-dependent manner. Cytotoxicity of this compound is found to be
      mediated by a caspase-dependent apoptosis. Also, there were indications of
      caspase independent apoptosis as z-VAD-FMK failed to fully rescue the cells from
      5'-Cl-induced apoptosis. In addition, the compound triggered generation of
      Reactive Oxygen Species (ROS), caused depolarization of the mitochondrial inner
      membrane, decreased the level of cellular ATP, modulated the expression and
      phosphorylation of Bcl-2 leading to loss of its association with Bax and
      increased the release of cytochrome c to the cytosol of treated cells. The
      effects of 5'-Cl on mitochondria and apoptosis were substantially blocked in the
      presence of a combination between z-VAD-FMK and either of the ROS scavenger N
      acetyl-L-cysteine (NAC) or pyrrolidine dithiocarbamate (PDTC). CONCLUSION: We
      demonstrated that the growth inhibitory effects of 5'-Cl in HL-60 cells involve
      multiple pathways of apoptosis and dysregulation of mitochondrial functions.

PMID- 25871325
TI  - Right hemisphere neural activations in the recall of waking fantasies and of
      dreams.
AB  - The story-like organization of dreams is characterized by a pervasive bizarreness
      of events and actions that resembles psychotic thought, and largely exceeds that
      observed in normal waking fantasies. Little is known about the neural correlates
      of the confabulatory narrative construction of dreams. In this study, dreams,
      fantasies elicited by ambiguous pictorial stimuli, and non-imaginative first- and
      third-person narratives from healthy participants were recorded, and were then
      studied for brain blood oxygen level-dependent functional magnetic resonance
      imaging on a 3.0-Tesla scanner while listening to their own narrative reports and
      attempting a retrieval of the corresponding experience. In respect to non-bizarre
      reports of daytime activities, the script-driven recall of dreams and fantasies
      differentially activated a right hemisphere network including areas in the
      inferior frontal gyrus, and superior and middle temporal gyrus. Neural responses
      were significantly greater for fantasies than for dreams in all regions, and
      inversely proportional to the degree of bizarreness observed in narrative
      reports. The inferior frontal gyrus, superior and middle temporal gyrus have been
      implicated in the semantic activation, integration and selection needed to build
      a coherent story representation and to resolve semantic ambiguities; in deductive
      and inferential reasoning; in self- and other-perspective taking, theory of mind,
      moral and autobiographical reasoning. Their degree of activation could parallel
      the level of logical robustness or inconsistency experienced when integrating
      information and mental representations in the process of building fantasy and
      dream narratives. 

PMID- 25871326
TI  - Aromaticity as stabilizing element in the bidentate activation for the catalytic
      reduction of carbon dioxide.
AB  - A new transition-metal-free mode for the catalytic reduction of carbon dioxide
      via bidentate interaction has been developed. In the presence of Li2[1,2
      C6H4(BH3)2], CO2 can be selectively transformed to either methane or methanol,
      depending on the reducing agent. The bidentate nature of binding is supported by
      X-ray analysis of an intermediate analogue, which experiences special
      stabilization due to aromatic character in the bidentate interaction. Kinetic
      studies revealed a first-order reaction rate. The transformation can be conducted
      without any solvent. 

PMID- 25871327
TI  - Improving performance and lifetime of small-molecule organic photovoltaic devices
      by using bathocuproine-fullerene cathodic layer.
AB  - In this study, we compared the use of neat bathocuproine (BCP) and BCP:C60 mixed
      buffer layers in chloroboron subphthalocyanine (SubPc)/C60 bilayer organic
      photovoltaic (OPV) devices and analyzed their influence on device performance.
      Replacing the conventional BCP with BCP:C60 enabled manipulating the optical
      field distribution for optimizing the optical properties of the devices.
      Estimation of the interfacial barrier indicated that the insertion of the BCP:C60
      between the C60 and electrode can effectively reduce the barrier for electrons
      and enhance electron collection at the electrode. Temperature-dependent
      measurements of the OPV devices performed to calculate the barrier height at the
      SubPc/C60 interface suggested that band bending was larger when the BCP:C60
      buffer layer was used, reflecting increased exciton dissociation efficiency. In
      addition, the device lifetime was considerably improved when the BCP:C60 buffer
      layer was used. The device performance was stabilized after the photodegradation
      of the active layers, thereby increasing the device lifetime compared with the
      use of the neat BCP buffer layer. Atomic force microscopy images showed that the
      neat BCP was easily crystallized and could degrade the cathodic interface,
      whereas the blend of C60 and BCP suppressed the crystallization of BCP.
      Therefore, the optimal buffer layer improved both the device performance and the
      device lifetime. 

PMID- 25871328
TI  - QuickSilver: A Phase II Study Using Magnetic Resonance Imaging Criteria to
      Identify "Good Prognosis" Rectal Cancer Patients Eligible for Primary Surgery.
AB  - BACKGROUND: Recently, two nonrandomized, prospective cohort studies used magnetic
      resonance imaging (MRI) to assess the circumferential resection margin to
      identify "good prognosis" rectal tumors eligible for primary surgery and have
      reported favorable outcomes. OBJECTIVE: The objective of this project was to
      conduct a Phase II trial to assess the safety and feasibility of MRI criteria to
      identify "good prognosis" rectal tumors eligible for primary surgery in the North
      American setting. METHODS: Patients with newly diagnosed primary rectal cancer
      attending surgical clinics at participating centers will be invited to
      participate in the study. The inclusion criteria for the study are: (1) diagnosis
      of rectal cancer (0-15 cm) from the anal verge on endoscopy and proximal extent
      of tumor at or below the sacral promontory on computed tomography (CT) or MRI;
      (2) meets all MRI criteria for "good prognosis" rectal tumor as defined by the
      study protocol; (3) 18 years or older; and (4) able to provide written consent.
      The initial assessment will include: (1) clinical and endoscopic examination of
      the primary tumor; (2) CT chest, abdomen, and pelvis; and (3) pelvic MRI. All
      potentially eligible cases will be presented at a multidisciplinary cancer
      conference to assess for eligibility based on the MRI criteria for "good
      prognosis" tumor which include: (1) predicted circumferential resection margin
      (CRM) > 1 mm; (2) definite T2, T2/early T3, or definite T3 tumor with < 5 mm of
      extramural depth of invasion (EMD); (3) any N0, N1, or N2; and (4) absence of
      extramural venous invasion (EMVI). All patients fulfilling the MRI criteria for
      "good prognosis" rectal cancer and the inclusion and exclusion criteria will be
      invited to participate in the study and proceed to primary surgery. The safety of
      the MRI criteria will be evaluated by assessing the positive CRM rate and is the
      primary outcome for the study. RESULTS: We expect to have a minimum of 300
      potentially eligible patients, and based on a 30% eligibility rate and 80%
      participation rate, it is expected that 75 patients will be recruited over the
      two year study period. A Data Safety Monitoring Committee has been organized, and
      the study will be stopped if a positive CRM of >10% is reported at any interim
      assessment, which will occur after every 25 patients accrued in the study.
      CONCLUSIONS: It is expected that the results of this study will show that use of
      MRI criteria to identify "good prognosis" rectal cancers eligible for primary
      surgery will be safe (ie, positive margin less than 10%). Therefore, these
      results will have significant potential to change the current management of
      rectal cancer in North America and result in improved quality of life for rectal
      cancer patients and survivors, while reducing overall health care costs. TRIAL
      REGISTRATION: ISRCTN05107772; http://www.controlled-trials.com/ISRCTN05107772/
      (Archived by WebCite at http://www.webcitation/6WhhUhXkA).

PMID- 25871329
TI  - Natural antioxidants improve red blood cell "survival" in non-leukoreduced blood
      samples.
AB  - BACKGROUND: Blood collected in an anticoagulant can be kept refrigerated in an
      unmodified state within 5 - 6 weeks. Oxidative damage is considered to be a one
      of the major factors contributing to the development of storage lesions. Lipid
      and membrane proteins oxidation results in changes in cation gradients that
      affect the cell survival. AIM: In the present study we used the natural
      antioxidants and ion channels blockers (L-carnosine, spermine, phloretin and
      their mixtures) to prolong "survival" of red blood cells (RBCs), measured as the
      lack of PS exposure and cell hemolysis, in the Alsever's preservative solution
      upon hypothermic storage. RESULTS: We show that the mixture of carnosine (20 mM),
      spermine (20 uM) and phloretin (100 uM) effectively blunted phosphatidylserine
      (PS) exposure, Ca(2+) accumulation and RBCs hemolysis in non-leukoreduced low (~
      2%) hematocrit samples after 36 days of storage as well as after 1 day of post
      storage incubation of the stored cells in physiological saline solution. In
      addition, a slight but significant decrease in PS exposure was observed in non
      leukoreduced high (~ 20%) hematocrit samples after 36 days of storage with the
      mixture of substances. CONCLUSION: We conclude that the use of the mixture of
      natural antioxidants (carnosine, spermine, and phloretin) as an additive to blood
      preservative solution provides better RBCs storage and "survival".

PMID- 25871330
TI  - Seasonal recurrence of food bolus obstruction in eosinophilic esophagitis.
AB  - BACKGROUND: Eosinophilic esophagitis (EoE) is a newly recognised condition that
      is apparently increasing in prevalence, and the aetiology is poorly understood.
      The role of aeroallergens in EoE is controversial, given the success of dietary
      therapy. Massive aeroallergen exposure leading to food bolus obstruction events
      (FBOE) has been described, and the diagnosis of EoE by esophageal biopsy noted to
      be more common in the pollen season according to previous case series. AIM: To
      determine if a seasonal variation and a geographical variation occurred in EoE
      presenting as FBOE in adults, and to track the prevalence of FBOE and EoE over
      time. METHOD: A retrospective case-control study analysis was performed from
      January 2002 to January 2012 to identify all FBOE in adults presenting to five
      tertiary hospitals in Melbourne, Australia. Endoscopy, histopathological reports,
      case notes and blood tests were examined, and postcodes recorded. Records of
      pollen counts were obtained. Cases were defined according to esophageal biopsy
      and grouped based on month of diagnosis. All other causes of FBOE served as
      controls. RESULTS: One thousand, one hundred and thirty-two FBOE were identified.
      Biopsies were only performed in 278 of these cases, and 85 patients were found to
      have EoE after biopsy. Patients with EoE were younger (mean age 38 years, range
      18-72) compared with those with alternative diagnosis (mean age 64.4 range 22
      92), more likely to be male (M : F = 4:1 compared with 1.68:1 ) and had a higher
      eosinophil count in venous blood. Overall no seasonality was demonstrated in FBOE
      secondary to any diagnosis, although the six cases of recurrent FBOE secondary to
      EoE mainly occurred in the grass pollen season in subsequent years. FBOE cases
      were evenly distributed throughout metropolitan Melbourne irrespective of
      population density. EoE as a percentage of FBOE increased over time. CONCLUSION:
      Seasonal aeroallergens may be important for a subgroup of patients with EoE
      presenting as recurrent FBOE. Esophageal biopsies are performed in a minority of
      patients, representing a significant departure from ideal management and
      contributing to recurrent unnecessary FBOE. EoE is an increasingly important
      cause of FBOE.

PMID- 25871331
TI  - Comparison of CE-FDG-PET/CT with CE-FDG-PET/MR in the evaluation of osseous
      metastases in breast cancer patients.
AB  - BACKGROUND: Despite improvements in treatments, metastatic breast cancer remains
      difficult to cure. Bones constitute the most common site of first-time
      recurrence, occurring in 40-75% of cases. Therefore, evaluation for possible
      osseous metastases is crucial. Technetium 99 ((99)Tc) bone scintigraphy and
      fluorodexossyglucose (FDG) positron emission tomography (PET)-computed tomography
      (PET-CT) are the most commonly used techniques to assess osseous metastasis. PET
      magnetic resonance (PET-MR) imaging is an innovative technique still under
      investigation. We compared the capability of PET-MR to that of same-day PET-CT to
      assess osseous metastases in patients with breast cancer. METHODS: One hundred
      and nine patients with breast cancer, who underwent same-day contrast enhanced
      (CE)-PET-CT and CE-PET-MR, were evaluated. CE-PET-CT and CE-PET-MR studies were
      interpreted by consensus by a radiologist and a nuclear medicine physician.
      Correlations with prior imaging and follow-up studies were used as the reference
      standard. Binomial confidence intervals and a chi(2) test were used for
      categorical data, and paired t-test was used for the SUVmax data; a non
      informative prior Bayesian approach was used to estimate and compare the
      specificities. RESULTS: Osseous metastases affected 25 out 109 patients.
      Metastases were demonstrated by CE-PET-CT in 22 out of 25 patients (88%+/-7%),
      and by CE-PET-MR in 25 out of 25 patients (100%). CE-PET-CT revealed 90 osseous
      metastases and CE-PET-MR revealed 141 osseous metastases (P<0.001). The estimated
      sensitivity of CE-PET-CT and CE-PET-MR were 0.8519 and 0.9630, respectively. The
      estimated specificity for CE-FDG-PET-MR was 0.9884. The specificity of CE-PET-CT
      cannot be determined from patient-level data, because CE-PET-CT yielded a false
      positive lesion in a patient who also had other, true metastases. CONCLUSIONS: CE
      PET-MR detected a higher number of osseous metastases than did same-day CE-PET
      CT, and was positive for 12% of the patients deemed osseous metastasis-negative
      on the basis of CE-PET-CT.

PMID- 25871333
TI  - Antimicrobial coatings with dual cationic and N-halamine character:
      characterization and biocidal efficacy.
AB  - A method to prepare an antimicrobial coating for food-handling materials is
      reported. Alternating layers of branched polyethylenimine and styrene maleic
      anhydride copolymer were applied onto the surface of polypropylene. The resulting
      coatings had low surface energy and presented enhanced antimicrobial character
      due to the presence of both cationic and N-halamine forming structures. In its
      unchlorinated form, the coating inactivated Listeria monocytogenes by ~3
      logarithmic cycles. In the form of N-halamines >5 logarithmic cycles were
      reached. Microbial inactivation kinetics showed a Weibullian behavior when the
      coating was unchlorinated and a sigmoidal behavior when chlorinated. Microscopy
      confirmed that the reduction in the microbial load was due to biocidal effects of
      the coating and not bacterial adhesion onto the modified surface. The modified
      surface was able to be repeatedly rechlorinated. Such rechargeable antimicrobial
      coatings may support improving food safety by reducing cross-contamination of
      microorganisms from food-processing equipment. 

PMID- 25871332
TI  - The impact of comprehensive geriatric assessment interventions on tolerance to
      chemotherapy in older people.
AB  - BACKGROUND: Although comorbidities are identified in routine oncology practice,
      intervention plans for the coexisting needs of older people receiving
      chemotherapy are rarely made. This study evaluates the impact of geriatrician
      delivered comprehensive geriatric assessment (CGA) interventions on chemotherapy
      toxicity and tolerance for older people with cancer. METHODS: Comparative study
      of two cohorts of older patients (aged 70+ years) undergoing chemotherapy in a
      London Hospital. The observational control group (N=70, October 2010-July 2012)
      received standard oncology care. The intervention group (N=65, September 2011
      February 2013) underwent risk stratification using a patient-completed screening
      questionnaire and high-risk patients received CGA. Impact of CGA interventions on
      chemotherapy tolerance outcomes and grade 3+ toxicity rate were evaluated.
      Outcomes were adjusted for age, comorbidity, metastatic disease and initial dose
      reductions. RESULTS: Intervention participants undergoing CGA received mean of
      6.2+/-2.6 (range 0-15) CGA intervention plans each. They were more likely to
      complete cancer treatment as planned (odds ratio (OR) 4.14 (95% CI: 1.50-11.42),
      P=0.006) and fewer required treatment modifications (OR 0.34 (95% CI: 0.16-0.73),
      P=0.006). Overall grade 3+ toxicity rate was 43.8% in the intervention group and
      52.9% in the control (P=0.292). CONCLUSIONS: Geriatrician-led CGA interventions
      were associated with improved chemotherapy tolerance. Standard oncology care
      should shift towards modifying coexisting conditions to optimise chemotherapy
      outcomes for older people.

PMID- 25871334
TI  - Metal Ions Mediated Morphology and Phase Transformation of Chalcogenide
      Semiconductor: From CuClSe2 Microribbon to CuSe Nanosheet.
AB  - Foreign ions are of significant importance in controlling and modulating the
      morphology of semiconductor nanocrystals during the colloidal synthesis process.
      Herein, we demonstrate the potential of foreign metal ions to simultaneously
      control the morphology and crystal phase of chalcogenide semiconductors. The
      results indicate that the introduction of Al(3+) ions can induce the structural
      transformation from monoclinic CuClSe2 microribbons (MRs) to klockmannite CuSe
      nanosheets (NSs) and the growth of large-sized CuSe NSs. The as-prepared
      micrometer-sized CuSe NSs exhibit a high-conducting behavior, long-term
      durability, and environment stability. The novel properties enable CuSe NSs to
      open up a bright prospect for printable electrical interconnects and flexible
      electronic devices. 

PMID- 25871335
TI  - Chronic Pain in Multiple Sclerosis Patients: Utility of Sensory Quantitative
      Testing in Patients with Fibromyalgia Comorbidity.
AB  - BACKGROUND: Lower thermal and discomfort thresholds may predispose multiple
      sclerosis (MS) patients to chronic pain, but a possible effect of fibromyalgia
      (FM) comorbidity has never been investigated. Aims were to investigate the
      thermal and discomfort thresholds in the evaluation of pain intensity between MS
      patients with FM (PFM+) and MS patients with pain not associated to FM (PFM-).
      METHODS: One hundred thirty three MS patients were investigated for chronic pain.
      FM was assessed according to the 1990 ACR diagnostic criteria. An algometer was
      used to measure the thresholds in the patients and 60 matched healthy subjects.
      RESULTS: Chronic pain was present in 88 (66.2%) patients; 12 (13.6%) had
      neuropathic pain, 22 (17.3%) were PFM+ and 65 (48.9%) PFM-. PFM+ were
      predominantly female (p = 0.03) and had a greater EDSS (p = 0.01) than NoP; no
      other significant differences emerged than PFM-. The thresholds were lower in MS
      patients than controls (p < 0.01), mainly in the PFM+. FM severity influenced the
      thermal threshold (p < 0.001), while the female gender influenced the discomfort
      threshold (p < 0.001). CONCLUSION: Thermal and discomfort thresholds were lower
      in patients than controls and were the lowest in PFM+. Their more severely
      impaired thermal threshold supports a neurophysiological basis of such
      association.

PMID- 25871336
TI  - Plasma lipoprotein(a) levels and atherosclerotic renal artery stenosis in
      hypertensive patients.
AB  - BACKGROUND/AIMS: The contribution of emergent cardiovascular risk factors to
      atherosclerotic renal artery stenosis (ARAS) is debated. We investigated the
      relationship of lipoprotein(a) and prothrombotic factors with ARAS in
      hypertension. METHODS: In 50 hypertensive patients with angiographic evidence of
      ARAS and 58 hypertensive patients who had comparable cardiovascular risk factor
      burden but no evidence of renovascular disease, we measured renal function,
      lipoprotein(a), homocysteine, and hemostatic-fibrinolytic markers. RESULTS:
      Patients with ARAS were more frequently smokers and had longer duration of
      hypertension, heavier antihypertensive treatment, and worse renal function than
      controls. Lipoprotein(a) was higher in patients with ARAS than controls, whereas
      no differences were found in homocysteine and all hemostatic variables.
      Multivariate analysis showed that lipoprotein(a) was associated with ARAS
      independent of other confounders including renal function and history of coronary
      heart, cerebrovascular, and peripheral artery disease. CONCLUSION: Lipoprotein(a)
      might contribute to the development of ARAS and detection of elevated levels of
      this lipoprotein could raise the suspicion of renovascular disease in patients
      with high blood pressure.

PMID- 25871337
TI  - HEDEN Pain Scale: A Shortened Behavioral Scale for Assessment of Prolonged Cancer
      or Postsurgical Pain in Children Aged 2 to 6 Years.
AB  - Few observational scales are available for assessing chronic or recurrent pain in
      children with cancer because overt behavioral signs of chronic pain dissipate as
      time passes, making them difficult to detect reliably. The Douleur Enfant Gustave
      Roussy (DEGR) scale developed by Gauvain-Piquard to monitor prolonged pain in
      children with cancer aged 2-6 years is currently the only validated tool
      available for this purpose, but is time consuming and difficult to use in daily
      clinical practice. To shorten composite measurement scales, we developed the
      Hetero Evaluation Douleur Enfant (HEDEN) scale from the DEGR scale. We present
      here the process and validation of this scale. Expert consensus was used for the
      elaboration of HEDEN: 5/10 DEGR items were chosen with three rating levels.
      Concurrent validity was tested in a first cohort with correlation analysis
      between HEDEN and DEGR. The HEDEN scale was then validated in a second cohort. In
      the first step, the study (59 children) showed acceptable correlation between
      DEGR and HEDEN (r = 0.5), with good reliability (alpha = 0.61), and interrater
      agreement (r = 0.62). Subsequent validation in 48 children showed a significant
      correlation between DEGR and HEDEN (r = 0.6). Reliability was good (alpha =
      0.75), with excellent interrater agreement [r = 0.67 (95% CI: 0.48-0.79)]. On
      average, the evaluation took 23 minutes (SD = 10.4) for DEGR versus 4.42 minutes
      (SD = 5.9) for HEDEN. This study shows a good correlation between HEDEN and DEGR
      scales. HEDEN allows accurate assessment of prolonged pain in young children with
      cancer. 

PMID- 25871338
TI  - Traditional Chinese medicine baicalin suppresses mESCs proliferation through
      inhibition of miR-294 expression.
AB  - BACKGROUND: Traditional Chinese herbal medicines (TCMs) have been widely used
      against a broad spectrum of biological activities, including influencing the
      cardiac differentiation from mouse embryonic stem cells (mESCs). However, their
      effects and mechanisms of action on ESCs proliferation remain to be determined.
      The present study aimed to determine the effect of three TCMs, baicalin,
      ginsenoside Rg1, and puerarin, on mESCs proliferation and to elucidate the
      possible mechanism of their action. METHODS: Cell proliferation was examined with
      a cell proliferation assay Cell Counting Kit-8 (CCK-8), propidium iodide (PI)
      staining was used to visualize cell cycle. The mRNA expression level of c-myc, c
      fos, c-jun, GAPDH and microRNAs were measured by quantitative real time RT-PCR.
      RESULTS: We found that baicalin 50 MUM suppressed the proliferation of mESCs as
      observations in more cells in G1 phase and less cells in either S phase or G2/M
      phase. Moreover, baicalin suppressed the expressions of c-jun and c-fos in mESCs
      and down-regulated the expression of miR-294. Overexpression of miR-294 in mESCs
      significantly reversed the effects of baicalin both on mESC proliferation and c
      fos/c-jun expression. CONCLUSIONS: Baicalin down-regulation of miR-294 may be its
      key mechanism of action in decreasing mESCs proliferation.

PMID- 25871339
TI  - Iodide Ion Pairing with Highly Charged Ruthenium Polypyridyl Cations in CH3CN.
AB  - A series of three highly charged cationic ruthenium(II) polypyridyl complexes of
      the general formula [Ru(deeb)3-x(tmam)x](PF6)2x+2, where deeb is 4,4'-diethyl
      ester-2,2'-bipyridine and tmam is 4,4'-bis[(trimethylamino)methyl]-2,2'
      bipyridine, were synthesized and characterized and are referred to as 1, 2, or 3
      based on the number of tmam ligands. Crystals suitable for X-ray crystallography
      were obtained for the homoleptic complex 3, which was found to possess D3
      symmetry over the entire ruthenium complex. The complexes displayed visible
      absorption spectra typical of metal-to-ligand charge-transfer (MLCT) transitions.
      In acetonitrile, quasi-reversible waves were assigned to Ru(III/II) electron
      transfer, with formal reduction potentials that shifted negative as the number of
      tmam ligands was increased. Room temperature photoluminescence was observed in
      acetonitrile with quantum yields of phi ~ 0.1 and lifetimes of tau ~ 2 MUs. The
      spectroscopic and electrochemical data were most consistent with excited-state
      localization on the deeb ligand for 1 and 2 and on the tmam ligand for 3. The
      addition of tetrabutylammonium iodide to the complexes dissolved in a CH3CN
      solution led to changes in the UV-vis absorption spectra consistent with ion
      pairing. A Benesi-Hildebrand-type analysis of these data revealed equilibrium
      constants that increased with the cationic charge 1 < 2 < 3 with K = 4000, 4400,
      and 7000 M(-1). (1)H NMR studies in CD3CN also revealed evidence for iodide ion
      pairs and indicated that they occur predominantly with iodide localization near
      the tmam ligand(s). The diastereotopic H atoms on the methylene carbon that link
      the amine to the bipyridine ring were uniquely sensitive to the presence of
      iodide; analysis revealed that an iodide "binding pocket" exists wherein iodide
      forms an adduct with the 3 and 3' bipyridyl H atoms and the quaternized amine.
      The MLCT excited states were efficiently quenched by iodide. Time-resolved
      photoluminescence measurements of 1 revealed a static component consistent with
      rapid electron transfer from iodide in the "binding pocket" to the Ru metal
      center in the excited state, ket > 10(8) s(-1). The possible relevance of this
      work to solar energy conversion and dye-sensitized solar cells is discussed. 

PMID- 25871340
TI  - Hikiamides A-C, Cyclic Pentadepsipeptides from Fusarium sp. TAMA 456.
AB  - Three new cyclic pentadepsipeptides, hikiamides A-C (1-3), were isolated from the
      culture extract of Fusarium sp. TAMA 456. The structures were determined by
      spectroscopic analysis using NMR and MS, and the absolute configurations were
      established by using Marfey's method and chiral HPLC analysis. Hikiamides induced
      the differentiation of murine ST-13 preadipocytes into mature adipocytes at 2 MUM
      and adiponectin mRNA expression (5- to 13-fold higher than control). They also
      induced PPAR-gamma-dependent gene expression at a concentration from 0.63 to 10
      MUM in a gene reporter assay. 

PMID- 25871341
TI  - Alcohol and sleep review: flawed design, methods, and statistics cannot support
      conclusions.

PMID- 25871342
TI  - Electrochemical Instability of Phosphonate-Derivatized, Ruthenium(III)
      Polypyridyl Complexes on Metal Oxide Surfaces.
AB  - The oxidative stability of the molecular components of dye-sensitized
      photoelectrosynthesis cells for solar water splitting remains to be explored
      systematically. We report here the results of an electrochemical study on the
      oxidative stability of ruthenium(II) polypyridyl complexes surface-bound to
      fluorine-doped tin oxide electrodes in acidic solutions and, to a lesser extent,
      as a function of pH and solvent with electrochemical monitoring. Desorption
      occurs for the Ru(II) forms of the surface-bound complexes with oxidation to
      Ru(III) enhancing both desorption and decomposition. Based on the results of long
      term potential hold experiments with cyclic voltammetry monitoring,
      electrochemical oxidation to Ru(III) results in slow decomposition of the complex
      by 2,2'-bipyridine ligand loss and aquation and/or anation. A similar pattern of
      ligand loss was also observed for a known chromophore-catalyst assembly for both
      electrochemical water oxidation and photoelectrochemical water splitting. Our
      results are significant in identifying the importance of enhancing chromophore
      stability, or at least transient stability, in oxidized forms in order to achieve
      stable performance in aqueous environments in photoelectrochemical devices. 

PMID- 25871343
TI  - Adaptation of international guidelines on assessment and management of cancer
      pain for the Australian context.
AB  - AIM: To develop clinical practice guidelines for screening, assessing and
      managing cancer pain in Australian adults. METHODS: This three-phase project
      utilized the ADAPTE approach to adapt international cancer pain guidelines for
      the Australian setting. A Working Party was established to define scope, screen
      guidelines for adaptation and develop recommendations to support better cancer
      pain control through screening, assessment, pharmacological and non
      pharmacological management, and patient education. Recommendations with limited
      evidence were referred to Expert Panels for advice before the draft guidelines
      were opened for public consultation via the Cancer Council Australia Cancer
      Guidelines Wiki platform in late 2012. All comments were reviewed by the Working
      Party and the guidelines were revised accordingly. RESULTS: Screening resulted in
      six international guidelines being included for adaptation - those developed by
      the Scottish Intercollegiate Guidelines Network (2008), National Health Service
      Quality Improvement Scotland (2009), National Comprehensive Cancer Network
      (2012), European Society of Medical Oncology (2011), European Association for
      Palliative Care (2011, 2012) and National Institute of Clinical Excellence
      (2012). Guideline adaptation resulted in 55 final recommendations. The guidelines
      were officially launched in November 2013. CONCLUSION: International guidelines
      can be efficiently reconfigured for local contexts using the ADAPTE approach.
      Availability of the guidelines via the Cancer Council Australia Wiki is intended
      to promote uptake and enable recommendations to be kept up to date. Resources to
      support implementation will also be made available via the Wiki if found to be
      effective by a randomized controlled trial commencing in 2015.

PMID- 25871344
TI  - Perceptions of similarity and response to selected comparison targets in type 2
      diabetes.
AB  - OBJECTIVE: Social comparisons (i.e. self-evaluations relative to others) may
      affect motivation for diabetes self-care behaviours. Comparisons can have either
      positive or negative effects, but it is not clear what differentiates these
      responses. This study tested the effect of a patient's perceived similarity to a
      comparison target on motivation for self-care. DESIGN: Individuals with type 2
      diabetes (n = 180, MA1c = 7.59%) selected to read one of four brief descriptions
      of a patient with diabetes. MAIN OUTCOME MEASURES: Participants rated their
      motivation for self-care behaviours prior and subsequent to reading and reported
      the extent to which they focused on similarities between the self and the
      selected patient while reading. RESULTS: Perceived similarity moderated the
      effect of selection on motivation for self-care (p = .01, eta2 = .06). Increased
      motivation was observed if participants focused on similarities with patients
      'doing better' (i.e. high coping effectiveness/low symptom severity) and
      decreased motivation if they focused on similarities with patients 'doing worse'
      (low coping effectiveness/high symptom severity). CONCLUSIONS: Providing social
      comparison information in diabetes management (and perhaps other chronic
      diseases) may improve motivation for self-care among some patients. A subset of
      patients, however, may benefit from guidance to focus on similarities with
      certain targets.

PMID- 25871345
TI  - Expanding the spectrum of livedoid vasculopathy: peculiar neuromuscular
      manifestations.

PMID- 25871346
TI  - Morphological effects of mitomycin C on urothelial responses to experimentally
      induced urethral stricture in rats.
AB  - OBJECTIVES: To analyze the urothelial responses to mitomycin C treatment after
      urethral injury in rats, as the urothelium might play a role in the pathogenesis
      of urethral stricture. METHODS: Male Sprague-Dawley rats were divided into four
      groups (n = 5/group): negative control, positive control without further
      treatment, experimental control treated with sodium hyaluronate and sodium
      carboxymethylcellulose, and experimental treated with mitomycin C after internal
      urethrotomy. RESULTS: Compared with negative controls, positive controls showed a
      significant increase in cell proliferation and DNA damage accompanied by a
      considerable decrease in DNA repair in the urothelium, which resulted in urethral
      stricture. Experimental controls showed a significant increase in cell
      proliferation, DNA damage and DNA repair compared with negative controls. The
      mitomycin C-treated group showed a significant decrease in cell proliferation and
      DNA damage, but a considerable increase in DNA repair compared with the positive
      and experimental control groups. DNA damage was immediately increased after
      urethral injury, but DNA repair and cell proliferation showed belated and
      upregulated expression after mitomycin C treatment. CONCLUSIONS: Mitomycin C
      could induce healthy re-epithelialization without severe damage in the
      urothelium. This finding might support the possibility of using mitomycin C as an
      adjuvant therapy for urethral strictures, and it might also suggest a urothelial
      role in the process of urethral stricture after urethral injury.

PMID- 25871348
TI  - Confusion, inequity and inconsistency: Abortion in Australia.

PMID- 25871347
TI  - Identification and Validation of Differential Phosphorylation Sites of the
      Nuclear FOXL2 Protein as Potential Novel Biomarkers for Adult-Type Granulosa Cell
      Tumors.
AB  - Granulosa cell tumor (GCT) is a rare form of ovarian cancer classified as a sex
      cord-stromal tumor. The c.402C->G missense mutation in the FOXL2 gene that
      changes cysteine 134 to tryptophan (C134W) is found in more than 97% of adult
      type GCTs, and the C134W FOXL2 mutant is hyperphosphorylated. We identified three
      differential phosphorylation sites, at serine 33 (S33), tyrosine 186 (Y186), and
      serine 238 (S238), of the C134W mutant by tandem mass spectrometry. Among these
      sites, antibodies were raised against the pS33 and pY186 epitopes using specific
      peptides, and they were tested by immunostaining tissue microarrays of archival
      adult-type GCT specimens, other tumors, and normal tissues. The pS33 antibody
      showed greater sensitivity and specificity for the detection of adult-type GCTs
      than that of the other phospho and nonphospho antibodies. The specificity of the
      pS33 antibody to the pS33 epitope was further confirmed by enriching the pS33
      peptide by affinity chromatography using the immobilized antibody, followed by
      mass spectrometric and western blot analyses from whole cell lysates of the adult
      type GCT cell line, KGN. pS33 FOXL2 immunostaining levels were significantly
      higher in adult-type GCTs than those in other tumors and tissues. The receiver
      operating characteristic curve analysis of pS33 FOXL2 showed high sensitivity
      (1.0) and specificity (0.76) to adult-type GCTs with a cutoff score of >30%
      positive cells, and the area under the curve was 0.96. This suggests the
      potential of pS33 FOXL2 to serve as a new biomarker for the diagnosis of adult
      type GCT. 

PMID- 25871349
TI  - Assessment techniques and South African community studies of trauma and
      posttraumatic stress disorder in children and adolescents.
AB  - This paper reviews: (i) trauma and posttraumatic stress disorder (PTSD)
      assessment instruments currently in use and (ii) trauma and PTSD studies in South
      African children and adolescents. Rates of trauma exposure in South African
      children and adolescents range from 40% to 100% and rates of PTSD range from 6%
      to 22%. Although many reliable and valid assessment instruments are available in
      the trauma field, comparison across trauma studies is made difficult by the
      differing methodologies and assessment techniques. 

PMID- 25871350
TI  - Visual-motor integration functioning in a South African middle childhood sample.
AB  - Visual-motor integration functioning has been identified as playing an integral
      role in different aspects of a child's development. Sensory-motor development is
      not only foundational to the physical maturation process, but is also imperative
      for progress with formal learning activities. Deficits in visual-motor
      integration have been identified as precursors of later learning disabilities and
      other neurological conditions. The primary aim of this study was to determine the
      status of visual-motor integration functioning of a group of learners from a
      disadvantaged peri-urban South African community. Visual-motor integration
      functioning was assessed using the Developmental Test of Visual-Motor Integration
      (VMI) and the Goodenough-Harris Drawing Test (GHD). Three hundred and thirty-nine
      learners in grades 1-4 were assessed and results for the group relative to
      gender, chronological age and socioeconomic status are reported. For the group,
      the mean test age fell 16 months below the mean chronological age on the VMI. The
      mean GHD score for the group was about a half a standard deviation below the
      GHD's test norm. At school entry level, visual-motor integration was more than
      one standard deviation below the mean. Compared to female learners, male learners
      achieved significantly higher scores on the test age score of the VMI (mean
      difference = 8.69 months), and the intelligence coefficient score of the GHD
      (mean difference = 4.68). Scores on both measures increased as a function of
      socioeconomic status. The VMI and GHD scores were significantly correlated (r =
      0.45; P < 0.01) suggesting that visual-motor integration is integral to
      intellectual functioning. 

PMID- 25871351
TI  - A successful cognitive-behavioural intervention that failed: a case study of
      adolescent conduct disorder at a school for the disadvantaged.
AB  - Conduct Disorder (CD) is a widespread problem in southern Africa. The aim of the
      study was to design, implement and evaluate a multi-modal cognitive-behavioural
      intervention based on treatments developed overseas, in order to investigate
      whether this approach can be transported to a South African school for deprived
      children. The target adolescent had a history of severely disruptive behaviour
      and was facing expulsion from a shelter for homeless children and his school. A
      thorough assessment served as the basis for a case formulation and treatment
      plan. Intervention included 23 individual sessions focussing on bereavement and
      the learning of self-control skills and prosocial behaviours, as well as
      contingency management training for school and shelter staff. Progress was
      tracked with a behaviour checklist completed daily by the teacher and regular
      interviews with school and shelter staff. After four months, the disruptive
      behaviour was eliminated. However, he was involved in stealing with some other
      learners and expelled anyway. Nevertheless the case study provides evidence for
      the transportability of the cognitive-behavioural approach to this kind of
      setting and documents the way in which a comprehensive intervention can be
      tailored to the needs of a child with a severely deprived background and little
      social support. 

PMID- 25871352
TI  - A parent's guide to Asperger's Syndrome and High-functioning Autism - how to meet
      the challenge and help your child thrive by Sally Ozonoff, Geraldine Dawson and
      James Mcpartland.

PMID- 25871353
TI  - Blackwell handbook of childhood cognitive development by usha goswami (editor).

PMID- 25871354
TI  - The metaphor of play: origin and breakdown of personal being by russell meares.

PMID- 25871355
TI  - The presence of the therapist - treating childhood trauma by monica lanyado.

PMID- 25871356
TI  - 15th Biennial South African Association of South African Child and Adolescent
      Psychiatry and Allied Professions (SAACAPAP) Conference 2005.

PMID- 25871357
TI  - Monitoring the rights and well-being of South African children?

PMID- 25871358
TI  - Treating severely traumatised children and adolescents using sensory integration,
      attachment theory and clinical reasoning.

PMID- 25871360
TI  - A New Method to Measure the Subpubic Arch Angle Using 3-D Ultrasound.
AB  - OBJECTIVES: The aim of this study was to assess the reproducibility of both a new
      contrast-enhancing technique (Oblique View eXtended Imaging, OVIX; Samsung) and
      the recently reported 3-D multiplanar technique (MPT) in the measurement of the
      subpubic angle (SPA) among a group of women at term gestation. In addition, we
      aimed to study the intermethod agreement between the OVIX technique and MPT.
      METHODS: We acquired a transperineal 3-D ultrasound volume from 155 women with a
      singleton uncomplicated term pregnancy before the onset of labor. Each 3-D
      dataset was analyzed by the MPT and OVIX algorithm. The angle formed by the lower
      edges of the pubic rami (SPA) was measured twice by an operator and once by
      another operator for each technique in order to assess intra- and interobserver
      reproducibility. Reproducibility and intermethod agreement were studied by means
      of the intraclass correlation coefficient (ICC) and Bland-Altman method. RESULTS:
      SPA measurements performed with OVIX showed high intraobserver [ICC 0.912, 95%
      confidence interval (CI) 0.882-0.935] and good interobserver (ICC 0.791, 95% CI
      0.724-0.844) agreement, while those measured with MPT showed moderate
      intraobserver (ICC 0.573, 95% CI 0.457-0.670) and good interobserver (ICC 0.640,
      95% CI 0.537-0.724) agreement. Whereas the intermethod analysis showed good
      agreement between the MPT and the OVIX techniques (ICC 0.614, 95% CI 0.414
      0.757), the SPA measured by MPT were significantly wider than those measured by
      OVIX (125 +/- 12 vs. 120 +/- 11 degrees , p = 0.006). CONCLUSIONS: OVIX is a
      reliable technique for SPA measurement. MPT overestimates the SPA in comparison
      with OVIX. Further studies are needed to assess its clinical utility.

PMID- 25871361
TI  - Indications for renal autotransplant: an overview.
AB  - Advances in transplantation led to the first renal autotransplant in 1963
      performed due to high ureteral injury sustained during aortic surgery. The
      procedure involves excision of the kidney and autologous re-implantation.
      Subsequently, multiple cases of renal autotransplantation have been reported in
      the literature for a range of indications. This reviews aims to assess the
      literature and experiences reported to assess the varying indications for renal
      autotransplant. The evidence and literature generated from experiences in this
      procedure are largely limited to case reports and relatively small or moderately
      sized case series. The main indications reported for performing autotransplant
      broadly includes renovascular disease, ureteral pathology and neoplastic disease.
      The advent of laparoscopic techniques and their implications on renal
      autotransplant also are discussed. Varying degrees of success are reported with
      this procedure with controversial issues surrounding this procedure remain,
      particularly in the area of neoplastic surgery. Renal autotransplant may be a
      useful last resort in preventing kidney loss in highly selected circumstances and
      when conventional methods have failed. 

PMID- 25871362
TI  - Respiratory complications after solid-organ transplantation.
AB  - The risk for respiratory complications after solid-organ transplantation
      continues to be high, even though progress has been achieved with surgical
      techniques, immunosuppressive agents, and perioperative treatment of transplant
      recipients. This review is an overview of infectious and noninfectious
      respiratory complications in liver, kidney, heart, and lung transplant patients.
      Postoperative respiratory complications are more frequent after liver, heart, and
      lung transplant recipients, but the incidence is lower in kidney transplant
      recipients. Lung infiltrates due to multidrug-resistant bacterial infections are
      increasing and may cause respiratory failure associated with high morbidity and
      mortality. Treatment strategies including early, broad-spectrum empiric
      antibiotic therapy, lung protective mechanical ventilation, and appropriate
      timing of tracheotomy for patients who need prolonged mechanical ventilation.
      Early recognition and aggressive treatment of these respiratory complications may
      improve outcomes. 

PMID- 25871363
TI  - Extension of right renal vein in renal transplant from deceased donors: cohort
      study.
AB  - OBJECTIVES: Throughout the world, 45 000 kidney transplants are performed per
      year. Graft and overall survival vary according to the type of donor (living or
      deceased donor). Anastomosis of a short renal vein with iliac vein or common
      external iliac vein has been associated with technical problems such as
      angulation of the vein or tension on the anastomosis, which could limit
      visualization and control of bleeding from the graft. The main objective of our
      study was to analyze patients undergoing deceased-donor kidney transplant and
      compare results in patients who had extension of the right renal vein with a
      patch of vena cava from the same donor versus patients who received the left
      kidney. MATERIALS AND METHODS: A prospective cohort study was performed from
      December 31, 2007 to December 31, 2009. We compared 2 patients groups. We used
      statistical software (R, Version 2.5.1). The analyzing team was blinded to the
      surgical technique, and informed consent was obtained from all patients. RESULTS:
      There was no statistically significant difference in surgical time (P > .85) or
      ultrasonographic parameters between groups, but it was possible to perform an
      easier vein anastomosis with the vena cava graft in right kidney transplant.
      CONCLUSIONS: We recommend considering our procedure with the vena cava graft in
      right kidney as an alternative option to decrease warm ischemia time, perform an
      easier vein anastomosis with the vena cava extension, and make the procedure
      comfortable for the surgeon.

PMID- 25871364
TI  - Hypothermic machine perfusion permits extended cold ischemia times with improved
      early graft function.
AB  - OBJECTIVES: The logistics of deceased-donor renal transplants are largely
      affected by cold ischemia time. However, to attain successful outcomes, other
      issues must be considered. Extending cold ischemia time to accommodate these
      issues would be valuable. We investigated the role of hypothermic machine
      perfusion to extend cold ischaemia time. MATERIALS AND METHODS: Deceased-donor
      kidneys were allocated to a storage method, depending on predicted time to
      operation. Kidneys to be transplanted from 8:00 AM to 8:00 PM in the transplant
      room remained in static cold storage. If predicted operating time was out of
      hours, the kidney was transferred to hypothermic machine perfusion and
      transplanted at the earliest opportunity on the dedicated transplant list.
      RESULTS: There were 74 kidneys transplanted from hypothermic machine perfusion
      and 101 kidneys from static cold storage. Median cold ischemia time was 23.85
      hours in the hypothermic machine perfusion group, compared with 13 hours in the
      static cold storage group (P <= .0001). There were 20 kidneys (27%) from
      hypothermic machine perfusion that had delayed graft function, compared with 47
      kidneys (47%) in the static cold storage group (P = .012). There were no other
      significant differences in graft or postoperative complications. CONCLUSIONS:
      This study demonstrated that improved early graft outcomes can be achieved
      following longer cold ischemia time by using hypothermic machine perfusion rather
      than static cold storage. This effect is likely multifactorial including the
      inherent effects of hypothermic machine perfusion, improved recipient
      preparation, and possibly better perioperative conditions.

PMID- 25871365
TI  - Dialysis within 24 hours of transplant does not improve graft function.
AB  - OBJECTIVES: Grafts from extended criteria donors, donors after cardiac death, and
      elderly donors have an increased risk of delayed graft function, lower graft
      survival, longer hospital stay, higher costs, and increased medical sequelae. A
      modifiable risk factor for delayed graft function may be the performance of
      dialysis on the same day as renal transplant. We reviewed our institutional
      experience to determine whether dialysis performed within 24 hours of engraftment
      increased the incidence or length of delayed graft function. MATERIALS AND
      METHODS: We retrospectively reviewed our kidney transplants performed between
      2008 and 2012. Preemptive transplants, transplants associated with peritoneal
      dialysis, potassium > 5 mmol/L, or living donors, and cases with insufficient
      information were excluded. Data collected included demographic, biochemical,
      donor, operative, and outcome variables (length of stay, length of delayed graft
      function, rejection, and a composite unfavorable outcome comprising cardiac and
      infectious events). Transplants that were associated with hemodialysis within 24
      hours before transplant (study group) were compared with the remainder of the
      cohort (control group). RESULTS: A total of 205 renal transplants were reviewed.
      There were 144 of 205 transplants (70.24%) in the study group, and the others
      comprised the control group. The rate of delayed graft function was 31% for the
      study group and 29% for control groups (P = .4959). Mean length of delayed graft
      function was 5.8 days for the study group and 6.1 days for control group (P =
      .7323). Delayed graft function risk factors such as donor age, terminal
      creatinine, and machine perfusion rate were similarly distributed across both
      groups. CONCLUSIONS: Normokalemic patients who did or did not undergo dialysis
      within 24 hours before transplant had equivalent incidence and duration of
      delayed graft function, graft outcomes, and patient outcomes. Therefore, dialysis
      within 24 hours before transplant is unnecessary in the setting of normokalemia.

PMID- 25871366
TI  - T-bet-positive mononuclear cell infiltration is associated with transplant
      glomerulopathy and interstitial fibrosis and tubular atrophy in renal allograft
      recipients.
AB  - OBJECTIVES: We aimed to study the role of T-bet-positive mononuclear cell
      infiltration in different compartments of kidney graft tissues in patients with
      chronic transplant glomerulopathy, interstitial fibrosis and tubular atrophy, and
      stable graft function. MATERIALS AND METHODS: There were 80 living-related renal
      transplant recipients included (chronic transplant glomerulopathy, n = 28;
      interstitial fibrosis and tubular atrophy, n = 28; stable graft function, n =
      24). Histologic characteristics and scoring for peritubular capillaritis,
      glomerulitis, interstitial fibrosis and tubular atrophy, and intimal arteritis
      were performed according to Banff 2007 classification and compared between the
      groups. Immunohistologic staining was performed for transcription factor T-bet, T
      bet mononuclear cells were counted, and T-bet infiltration score was compared
      between groups. RESULTS: Patients in different groups had similar clinical
      profiles and human leukocyte antigen mismatches, except the groups differed in
      serum creatinine and proteinuria. The prevalence and scoring of peritubular
      capillaritis and glomerulitis were significantly higher in chronic transplant
      glomerulopathy than interstitial fibrosis and tubular atrophy (P = .001) and
      stable graft function (P < .001). Tubulitis was observed in 6 patients (21.4%)
      with chronic transplant glomerulopathy but no patients with interstitial fibrosis
      and tubular atrophy. The C4d/donor-specific antibody was positive in 100%
      patients with chronic transplant glomerulopathy, 0% patients with interstitial
      fibrosis and tubular atrophy, and 4.1 % patients with stable graft function.
      Interstitial fibrosis and tubular atrophy was seen in 100% patients who had
      interstitial fibrosis and tubular atrophy; in patients who had chronic transplant
      glomerulopathy, 24 patients (85.7%) had interstitial fibrosis and 78.5% patients
      had tubular atrophy. The degree and severity of T-bet-positive cell infiltration
      were significantly higher in chronic transplant glomerulopathy than interstitial
      fibrosis and tubular atrophy or stable graft function; however, 85% patients with
      interstitial fibrosis and tubular atrophy also had T-bet-positive infiltration,
      suggesting a role of T-bet-positive cells in interstitial fibrosis and tubular
      atrophy. CONCLUSIONS: Chronic transplant glomerulopathy is a consequence of
      chronic active immune-mediated injury. Interstitial fibrosis and tubular atrophy
      may be associated with T-bet-positive mononuclear cell infiltration in the
      peritubular region. The T-bet infiltration should be evaluated in patients with
      chronic allograft injury.

PMID- 25871367
TI  - Outcome of kidney transplant with double ureter: a multicenter study.
AB  - OBJECTIVES: Renal transplant with double ureters is uncommon. However, with
      increasing numbers of en bloc and dual transplants from marginal donors, we
      frequently observe 2 ureters for implant. The current study reviewed our
      experience with 76 double-ureter renal transplants. MATERIALS AND METHODS: We
      performed a retrospective analysis of renal transplant performed in 2 institutes
      from 1996 to 2011. We recorded the outcomes of renal transplants with double
      ureters including complications. We compared outcomes with renal transplants with
      single ureters. RESULTS: Irrespective of the technique used for implant, we
      recorded no significant risk of complications of double, compared with single,
      ureter renal transplants. There were no significant differences in patient and
      graft survival. CONCLUSIONS: We believe that double-ureter transplant does not
      require additional risk discussion with the recipient because it is safe.
      However, when ureteral stents are used, we should ensure that a mechanism is in
      place for both stents to be removed postoperatively.

PMID- 25871368
TI  - Comparative factor analysis of the effect of postoperative peripheral parenteral
      nutrition on recovery of right lobe liver donors.
AB  - OBJECTIVES: Intensive nutritional support can reduce the catabolic response,
      improve protein synthesis, and promote liver regeneration. This study examined
      whether postoperative peripheral parenteral nutrition may improve recovery and
      reduce the length of hospital stay in right lobe liver donors. MATERIALS AND
      METHODS: In this retrospective study, we enrolled liver donors with residual
      liver volume < 50%. Donors were classified into 2 groups: donors who received (n
      = 44) or did not receive (n = 40) postoperative peripheral parenteral nutrition.
      Liver function tests included alanine aminotransferase and total bilirubin
      levels, and postoperative complications included pleural effusion, atelectasis,
      and wound complications. Hospital length of stay was included as a potential risk
      factor for the evaluation of the effect of postoperative peripheral parenteral
      nutrition on recovery of right lobe liver donors. RESULTS: Male sex (beta, 22.04;
      95% confidence interval: 6.22 - 37.86) was a significant predictor of changes in
      postoperative alanine aminotransferase level. Male sex (beta, 0.045; 95%
      confidence interval: 0.16 - 37.86) and receipt of peripheral parenteral nutrition
      (beta, -0.045; 95% confidence interval: -0.72 - 0.17) were significant predictors
      of changes in total bilirubin level. Postoperative atelectasis (P < .001),
      pleural effusion (P < .011), and total complications (P = .015) had significantly
      lower incidence in the peripheral parenteral nutrition than control group.
      Multivariate logistic regression showed that recipients of peripheral parenteral
      nutrition (odds ratio, 0.161; 95% confidence interval: 0.043 - 0.598) and age
      (odds ratio, 0.870; 95% confidence interval: 0.782 - 0.968) were significant
      preoperative risk factors for postoperative complications. CONCLUSIONS:
      Postoperative peripheral parenteral nutrition is associated with a lower
      incidence of pleural effusion and atelectasis, a more rapid recovery of
      hyperbilirubinemia, and shorter length of stay in right lobe liver donors.

PMID- 25871369
TI  - The effect of the Syrian crisis on organ transplantation in Syria.
AB  - The war in Syria that started in March 2011 has destroyed much of the country's
      infrastructure including many hospitals. The total number of kidney transplants
      performed in Syria in 2010 was 385 transplants before the number gradually
      declined to 154 transplants in 2013, a decrease of 60%. In addition, the number
      of operational kidney transplant centers has decreased from 8 to 4 centers.
      Unrelated-donor kidney transplant decreased from 70% during the years that
      preceded the crisis to 47% in 2013. More than 50% of physicians and surgeons
      involved in kidney transplant are not practicing transplant currently in their
      centers. Difficulties in the provision of immunosuppressive drugs for all
      patients in all provinces constitute a major challenge for the health authorities
      and transplant patients, especially patients who cannot arrange an alternate
      source. The project to initiate liver transplant came to a halt because foreign
      trainers could not visit Syria. The autologous bone marrow transplant program
      continued to function, but in a smaller and irregular manner. The commitment of
      transplant teams despite the large challenges was, and still is, extraordinary.
      In conclusion, all aspects of organ transplant have been affected, paralyzing new
      projects and negatively affecting existing programs. 

PMID- 25871370
TI  - Green polymer chemistry: investigating the mechanism of radical ring-opening
      redox polymerization (R3P) of 3,6-dioxa-1,8-octanedithiol (DODT).
AB  - The mechanism of the new Radical Ring-opening Redox Polymerization (R3P) of 3,6
      dioxa-1,8-octanedithiol (DODT) by triethylamine (TEA) and dilute H2O2 was
      investigated. Scouting studies showed that the formation of high molecular weight
      polymers required a 1:2 molar ratio of DODT to TEA and of DODT to H2O2. Further
      investigation into the chemical composition of the organic and aqueous phases by
      1H-NMR spectroscopy and mass spectrometry demonstrated that DODT is ionized by
      two TEA molecules (one for each thiol group) and thus transferred into the
      aqueous phase. The organic phase was found to have cyclic disulfide dimers,
      trimers and tetramers. Dissolving DODT and TEA in water before the addition of
      H2O2 yielded a polymer with Mn = 55,000 g/mol, in comparison with Mn = 92,000
      g/mol when aqueous H2O2 was added to a DODT/TEA mixture. After polymer removal,
      MALDI-ToF MS analysis of the residual reaction mixtures showed only cyclic
      oligomers remaining. Below the LCST for TEA in water, 18.7  degrees C, the system
      yielded a stable emulsion, and only cyclic oligomers were found. Below DODT/TEA
      and H2O2 1:2 molar ratio mostly linear oligomers were formed, with <20% cyclic
      oligomers. The findings support the proposed mechanism of R3P. 

PMID- 25871371
TI  - A facile synthesis and antimicrobial activity evaluation of sydnonyl-substituted
      thiazolidine derivatives.
AB  - Some new sydnonyl-substituted thiazolidine derivatives were synthesized in high
      yields by the modified Knoevenagel condensation of 3-aryl-4-formylsydnones with
      thiazolidine-2,4-dione and 2-thioxo-thiazolidine-4-one, respectively. All the
      synthesized thiazolidine derivatives were screened by paper-disc method to
      identify their antimicrobial activities against three bacteria viz.
      Staphylococcus aureus, Proteus vulgaris and Escherichia coli, and two fungal
      cultures viz. Aspergillus niger and Penicillium citrinum. The reference drugs
      were Norfloxacin and Griseofulvin, respectively. The screening data indicated
      that the tested sydnonyl-substituted thiazolidine derivatives exhibited no
      obvious antibacterial activity compared with the standard drug Norfloxacin.
      However, thiazolidine derivatives displayed significant antifungal activities
      against Penicillium citrinum and Aspergillus niger. Notably, all of the tested
      compounds showed growth inhibitory activity 1.5-4.4 times higher than that of the
      standard drug Griseofulvin against the two fungi. 

PMID- 25871372
TI  - Quercitrin, an inhibitor of Sortase A, interferes with the adhesion of
      Staphylococcal aureus.
AB  - Sortase A (SrtA) is a cysteine transpeptidase of most Gram-positive bacteria that
      is responsible for the anchorage of many surface protein virulence factors to the
      cell wall layer. SrtA mutants are unable to display surface proteins and are
      defective in the establishment of infections without affecting microbial
      viability. In this study, we report that quercitrin (QEN), a natural compound
      that does not affect Staphylococcus aureus growth, can inhibit the catalytic
      activity of SrtA in fibrinogen (Fg) cell-clumping and immobilized fibronectin
      (Fn) adhesion assays. Molecular dynamics simulations and mutagenesis assays
      suggest that QEN binds to the binding sites of the SrtA G167A and V193A mutants.
      These findings indicate that QEN is a potential lead compound for the development
      of new anti-virulence agents against S. aureus infections. 

PMID- 25871375
TI  - Ophthalmic research EVICR.net section--opening words.

PMID- 25871374
TI  - Methanolic extracts from brown seaweeds Dictyota cilliolata and Dictyota
      menstrualis induce apoptosis in human cervical adenocarcinoma HeLa cells.
AB  - Carcinoma of the uterine cervix is the second most common female tumor worldwide,
      surpassed only by breast cancer. Natural products from seaweeds evidencing
      apoptotic activity have attracted a great deal of attention as new leads for
      alternative and complementary preventive or therapeutic anticancer agents. Here,
      methanol extracts from 13 species of tropical seaweeds (Rhodophytas, Phaeophyta
      and Chlorophyta) collected from the Northeast of Brazil were assessed as
      apoptosis-inducing agents on human cervical adenocarcinoma (HeLa). All extracts
      showed different levels of cytotoxicity against HeLa cells; the most potent were
      obtained from the brown alga Dictyota cilliolata (MEDC) and Dictyota menstrualis
      (MEDM). In addition, MEDC and MEDM also inhibits SiHa (cervix carcinoma) cell
      proliferation. Studies with these two extracts using flow cytometry and
      fluorescence microscopy showed that HeLa cells exposed to MEDM and MEDC exhibit
      morphological and biochemical changes that characterize apoptosis as shown by
      loss of cell viability, chromatin condensation, phosphatidylserine
      externalization, and sub-G1 cell cycle phase accumulation, also MEDC induces cell
      cycle arrest in cell cycle phase S. Moreover, the activation of caspases 3 and 9
      by these extracts suggests a mitochondria-dependent apoptosis route. However,
      other routes cannot be ruled out. Together, these results point out the methanol
      extracts of the brown algae D. mentrualis and D. cilliolata as potential sources
      of molecules with antitumor activity. 

PMID- 25871373
TI  - Longevity extension by phytochemicals.
AB  - Phytochemicals are structurally diverse secondary metabolites synthesized by
      plants and also by non-pathogenic endophytic microorganisms living within plants.
      Phytochemicals help plants to survive environmental stresses, protect plants from
      microbial infections and environmental pollutants, provide them with a defense
      from herbivorous organisms and attract natural predators of such organisms, as
      well as lure pollinators and other symbiotes of these plants. In addition, many
      phytochemicals can extend longevity in heterotrophic organisms across phyla via
      evolutionarily conserved mechanisms. In this review, we discuss such mechanisms.
      We outline how structurally diverse phytochemicals modulate a complex network of
      signaling pathways that orchestrate a distinct set of longevity-defining cellular
      processes. This review also reflects on how the release of phytochemicals by
      plants into a natural ecosystem may create selective forces that drive the
      evolution of longevity regulation mechanisms in heterotrophic organisms
      inhabiting this ecosystem. We outline the most important unanswered questions and
      directions for future research in this vibrant and rapidly evolving field. 

PMID- 25871376
TI  - Neglected older women and men: Exploring age and gender as structural drivers of
      HIV among people aged over 60 in Uganda.
AB  - This study explored how women's and men's gendered experiences from childhood to
      old age have shaped their vulnerability in relation to HIV both in terms of their
      individual risk of HIV and their access to and experiences of HIV services. It
      was a small scale-scale study conducted in urban and rural sites in Uganda
      between October 2011 and March 2012. The study used qualitative methods: in-depth
      interviews (with 31 participants) and focus group discussions (FGDs) with older
      women (2) and men (2) in urban and rural sites and 7 key informant interviews
      (KIIs) with stakeholders from government and non-government agencies working on
      HIV issues. Women's position, the cultural management of sex and gender and
      contextual stigma related to HIV and to old age inter-relate to produce
      particular areas of vulnerability to the HIV epidemic among older women and men.
      Women report the compounding factor of gender-based violence marking many of
      their sexual relationships throughout their lives, including in older age. Both
      women and men report extremely fragile livelihoods in their old age. Older people
      are exposed to HIV through multiple and intersecting drivers of risk and
      represent an often neglected population within health systems. Research and
      interventions need to go beyond only conceptualising older people as 'carers' to
      better address their gendered vulnerabilities to HIV in relation to all aspects
      of policy and programming. 

PMID- 25871377
TI  - Ecological association between HIV and concurrency point-prevalence in South
      Africa's ethnic groups.
AB  - HIV prevalence between different ethnic groups within South Africa exhibits
      considerable variation. Numerous authors believe that elevated sexual partner
      concurrency rates are important in the spread of HIV. Few studies have, however,
      investigated if differential concurrency rates could explain differential HIV
      spread within ethnic groups in South Africa. This ecological analysis, explores
      how much of the variation in HIV prevalence by ethnic group is explained by
      differential concurrency rates. Using a nationally representative survey (the
      South African National HIV Prevalence, HIV Incidence, Behaviour and Communication
      Survey, 2005) the HIV prevalence in each of eight major ethnic groups was
      calculated. Linear regression analysis was used to assess the association between
      an ethnic group's HIV prevalence and the point-prevalence of concurrency. Results
      showed that HIV prevalence rates varied considerably between South Africa's
      ethnic groups. This applied to both different racial groups and to different
      ethnic groups within the black group. The point-prevalence of concurrency by
      ethnic group was strongly associated with HIV prevalence (R(2) = 0.83; p =
      0.001). Tackling the key drivers of high HIV transmission in this population may
      benefit from more emphasis on partner reduction interventions. 

PMID- 25871378
TI  - Inequalities in access to healthcare services among people living with HIV/AIDS
      in Nigeria.
AB  - The study investigated the magnitude of social inequities in access to subsidised
      healthcare services among people living with HIV and AIDS (PLWHA) in Nigeria.
      Structured interviews were conducted with 1 056 PLWHA selected from 60 community
      based support groups in 12 local government areas across 3 Nigerian states and
      the federal capital territory, using a multi-stage cluster sampling method. Data
      were collected on socio-economic characteristics of the respondents; awareness
      about location of health facilities; current health status; distance to
      facilities; and utilisation and expenditure on healthcare. The socio-economic
      characteristics of the respondents were used to compare their level of access to
      healthcare services from antiretroviral therapy (ART) sites and government
      hospitals. Awareness about location of health facilities was generally high
      (>=79%) among the respondents but higher among males, urban dwellers and those in
      highest wealth class (p < 0.05). About 60% of rural PLWHA and 55.2% of those in
      the lowest wealth class reported illness compared with 49.4% of urban residents
      and 47.4% of those in the highest wealth class. However, PLWHA in urban areas
      utilised government hospitals more than those in rural areas while rural PLWHA
      and those in the lowest wealth class travelled longer distances to ART sites (p <
      0.05). PLWHA in lowest wealth class and females faced catastrophic health
      expenditure of 67.6% and 55.5% of their monthly income respectively. Social
      inequities were observed in the subsidised HIV-treatment programme in Nigeria.
      Expansion of ART sites in rural areas and decentralisation of HIV care at
      government hospitals will reduce travel distance and transport costs and ensure
      universal access to healthcare services among PLWHA. 

PMID- 25871379
TI  - 'If the doctors see that they don't know how to cure the disease, they say it's
      AIDS': How older women in rural South Africa make sense of the HIV/AIDS epidemic.
AB  - South Africa, like other sub-Saharan African countries, is in the midst of the
      AIDS epidemic. Older women, here defined as aged 60 years and older, while at
      lower risk of infection than those aged 20-50, are amongst those deeply
      'affected' by the epidemic. In rural areas, older women, who have always played
      central roles in social reproduction in South African households and families,
      bear the brunt of care giving for the sick and dying. For this reason, it is
      important to explore how these women understand the epidemic. In South Africa,
      the prominence of traditional healers and medicine alongside biomedicine has led
      to multiple ways of perceiving, explaining and treating illness. This paper
      explores the various discourses older women in rural South Africa employ to make
      sense of the HIV/ AIDS epidemic in their daily lives. The aim is to better
      understand how these women construct the epidemic and how this knowledge can be
      used to benefit education and treatment endeavours in similar contexts. This
      paper draws on interview data collected as part of the Gogo Project conducted in
      the Medical Research Council (MRC)/Wits Rural Public Health and Health
      Transitions Research Unit. Sixty women between the ages of 60 and 75 years living
      in the rural Agincourt sub-district participated in three in-depth, semi
      structured interviews. The respondents in this study relied on a variety of
      discourses to make sense of the HIV/AIDS epidemic. They displayed a high level of
      knowledge based on biomedical education, however, they expressed ideas, often
      simultaneously, that seemed to contradict this education. Their ability to employ
      seemingly contradictory discourses represents the need to place the epidemic
      within familiar 'explanatory models' that are based on these women's life
      experiences and local knowledge. 

PMID- 25871380
TI  - Nutritional care and support among adults living with HIV at Hawassa Referral
      Hospital, southern Ethiopia: A qualitative study.
AB  - Background Improving nutritional care and support for people living with HIV
      (PLHIV) is an integral part of comprehensive HIV treatment according to the
      National Nutritional Strategy of Ethiopia. However, there is no adequate
      published study that assesses the nutritional care and support services for adult
      people living with HIV/ AIDS (PLHIV) in this setting. Objective The objective of
      the study was to identify the existing nutritional care and support services and
      determine the challenges facing adults living with HIV at Hawassa Referral
      Hospital in southern Ethiopia. Methods A qualitative study was carried out using
      focus group discussions (FGDs), in-depth interviews and participant observation.
      Four FDGs were held and five in-depth interviews were conducted. A two-week
      participant observation was also conducted by trained nurses. All interviews and
      FDGs were tape-recorded and transcribed; those conducted in Amharic were
      translated back to English. Finally thematic analysis of the transcripts was
      performed. Results Most of the FDG participants were unsatisfied with their
      nutritional care and support services and expressed difficulty with disclosing
      their HIV status for fear of stigma and discrimination. The in-depth interviews
      and participant observation showed results similar to those of the FDG. Some key
      informants expressed a fear that such poor nutritional care and support may
      threaten the quality of life of people living with HIV and suggested that all
      stakeholders work on improving the services. Conclusion Current nutritional care
      and support services for people living with HIV are not well coordinated. They
      focus mainly on monthly supplementation of antiretroviral drugs and occasional
      handouts of food. The need to provide health education on antiretroviral drugs
      and nutrition, and to emphasise strategies aimed at improving the nutritional
      status of peoples living with HIV is critical. Furthermore, the study recommended
      strengthening the initiatives of some organisations regarding sustainable income
      generating activities. 

PMID- 25871382
TI  - Editorial.

PMID- 25871381
TI  - TB/HIV-related training, knowledge and attitudes of community health workers in
      the Free State province, South Africa.
AB  - With its emphasis on task shifting and multi-trained and skilled outreach teams
      the primary healthcare (PHC) re-engineering strategy in South Africa depends on
      the training, knowledge and attitudes of community health workers (CHWs) to
      provide a variety of TB/HIV services. The aim of this exploratory research was to
      assess TB/ HIV-related training, knowledge and attitudes of CHWs. Interviews were
      conducted with 206 CHWs at 28 clinics in 1 urban and 2 rural sub-districts in the
      Free State province. Descriptive and bivariate analyses were performed using chi
      square, Kruskal-Wallis (H) and Mann-Whitney (U) tests for non-parametric data.
      More than half (54.9%) had not received basic training in HIV counselling and
      testing; almost one-third (31.1%) had not received basic training in TB/directly
      observed treatment (DOT) support. Furthermore, most CHWs had not received any
      follow-up training in HIV counselling and testing and in TB/DOT support.
      Significant associations (0.01 < p < 0.05) between the types of CHWs and their
      sub-district location, and their TB/HIV-related training, knowledge and attitudes
      were observed. In respect of the TB/HIV knowledge items assessed, a large
      majority (>95%) were knowledgeable, with only a few being ignorant about
      important facts related to TB/HIV. Lay counsellors were significantly more
      knowledgeable about TB/HIV than TB/DOT supporters and other CHWs were. Most CHWs
      disagreed with stigmatising statements about people with TB/HIV. The sub-district
      location of CHWs was significantly associated with their attitudes towards people
      with TB/HIV. CHWs in the two rural sub-districts were more likely to agree with
      stigmatising statements. In the context of PHC re-engineering, this exploratory
      research suggests that CHW TB/HIV training, knowledge and attitudes can and need
      to be improved if integrated TB/HIV services are to be successfully task-shifted
      to them in line with policy recommendations. 

PMID- 25871383
TI  - PI3K pan-inhibition impairs more efficiently proliferation and survival of T-cell
      acute lymphoblastic leukemia cell lines when compared to isoform-selective PI3K
      inhibitors.
AB  - Class I phosphatidylinositol 3-kinases (PI3Ks) are frequently activated in T-cell
      acute lymphoblastic leukemia (T-ALL), mainly due to the loss of PTEN function.
      Therefore, targeting PI3Ks is a promising innovative approach for T-ALL
      treatment, however at present no definitive evidence indicated which is the
      better therapeutic strategy between pan or selective isoform inhibition, as all
      the four catalytic subunits might participate in leukemogenesis. Here, we
      demonstrated that in both PTEN deleted and PTEN non deleted T-ALL cell lines,
      PI3K pan-inhibition exerted the highest cytotoxic effects when compared to both
      selective isoform inhibition or dual p110gamma/delta inhibition. Intriguingly,
      the dual p110gamma/delta inhibitor IPI-145 was effective in Loucy cells, which
      are representative of early T-precursor (ETP)-ALL, a T-ALL subtype associated
      with a poor outcome. PTEN gene deletion did not confer a peculiar reliance of T
      ALL cells on PI3K activity for their proliferation/survival, as PTEN was
      inactivated in PTEN non deleted cells, due to posttranslational mechanisms. PI3K
      pan-inhibition suppressed Akt activation and induced caspase-independent
      apoptosis. We further demonstrated that in some T-ALL cell lines, autophagy could
      exert a protective role against PI3K inhibition. Our findings strongly support
      clinical application of class I PI3K pan-inhibitors in T-ALL treatment, with the
      possible exception of ETP-ALL cases. 

PMID- 25871384
TI  - Multiple myeloma induces Mcl-1 expression and survival of myeloid-derived
      suppressor cells.
AB  - Myeloid-derived suppressor cells (MDSC) are contributing to an immunosuppressive
      environment by their ability to inhibit T cell activity and thereby promoting
      cancer progression. An important feature of the incurable plasma cell malignancy
      Multiple Myeloma (MM) is immune dysfunction. MDSC were previously identified to
      be present and active in MM patients, however little is known about the MDSC
      inducing and -activating capacity of MM cells. In this study we investigated the
      effects of the tumor microenvironment on MDSC survival. During MM progression in
      the 5TMM mouse model, accumulation of MDSC in the bone marrow was observed in
      early stages of disease development, while circulating myeloid cells were
      increased at later stages of disease. Interestingly, in vivo MDSC targeting by
      anti-GR1 antibodies and 5-Fluorouracil resulted in a significant reduced tumor
      load in 5TMM-diseased mice. In vitro generation of MDSC was demonstrated by
      increased T cell immunosuppressive capacity and MDSC survival was observed in the
      presence of MM-conditioned medium. Finally, increased Mcl-1 expression was
      identified as underlying mechanism for MDSC survival. In conclusion, our data
      demonstrate that soluble factors from MM cells are able to generate MDSC through
      Mcl-1 upregulation and this cell population can be considered as a possible
      target in MM disease. 

PMID- 25871385
TI  - Crosstalk between Desmoglein 2 and Patched 1 accelerates chemical-induced skin
      tumorigenesis.
AB  - Aberrant activation of Hedgehog (Hh) signaling is causative of BCCs and has been
      associated with a fraction of SCCs. Desmoglein 2 (Dsg2) is an adhesion protein
      that is upregulated in many cancers and overexpression of Dsg2 in the epidermis
      renders mice more susceptible to squamous-derived neoplasia. Here we examined a
      potential crosstalk between Dsg2 and Hh signaling in skin tumorigenesis. Our
      findings show that Dsg2 modulates Gli1 expression, in vitro and in vivo. Ectopic
      expression of Dsg2 on Ptc1(+/lacZ) background enhanced epidermal proliferation
      and interfollicular activation of the Hh pathway. Furthermore, in response to
      DMBA/TPA, the Dsg2/Ptc1+/lacZ mice developed squamous lessons earlier than the
      WT, Ptc1(+/lacZ), and Inv-Dsg2 littermates. Additionally, DMBA/TPA induced BCC
      formation in all mice harboring the Ptc1(+/lacZ) gene and the presence of Dsg2 in
      Dsg2/Ptc1(+/lacZ) mice doubled the BCC tumor burden. Reporter analysis revealed
      activation of the Hh pathway in the BCC tumors. However, in the SCCs we observed
      Hh activity only in the underlying dermis of the tumors. Furthermore,
      Dsg2/Ptc1(+/lacZ) mice demonstrated enhanced MEK/Erk1/2 activation within the
      tumors and expression of Shh in the dermis. In summary, our results demonstrate
      that Dsg2 modulates Hh signaling, and this synergy may accelerate skin tumor
      development by different mechanisms.

PMID- 25871386
TI  - Co-inhibition of polo-like kinase 1 and Aurora kinases promotes mitotic
      catastrophe.
AB  - Mitosis is choreographed by a number of protein kinases including polo-like
      kinases and Aurora kinases. As these kinases are frequently dysregulated in
      cancers, small-molecule inhibitors have been developed for targeted anticancer
      therapies. Given that PLK1 and Aurora kinases possess both unique functions as
      well as co-regulate multiple mitotic events, whether pharmacological inhibition
      of these kinases together can enhance mitotic catastrophe remains an outstanding
      issue to be determined. Using concentrations of inhibitors that did not induce
      severe mitotic defects on their own, we found that both the metaphase arrest and
      mitotic slippage induced by inhibitors targeting Aurora A and Aurora B (MK-5108
      and Barasertib respectively) were enhanced by a PLK1 inhibitor (BI 2536). We
      found that PLK1 is overexpressed in cells from nasopharyngeal carcinoma, a highly
      invasive cancer with poor prognosis, in comparison to normal nasopharyngeal
      epithelial cells. Nasopharyngeal carcinoma cells were more sensitive to BI 2536
      as a single agent and co-inhibition with Aurora kinases than normal cells. These
      observations underscore the mechanism and potential benefits of targeting PLK1
      and Aurora kinases to induce mitotic catastrophe in cancer cells. 

PMID- 25871387
TI  - Serum thioredoxin is a diagnostic marker for hepatocellular carcinoma.
AB  - Here we found that serum levels of thioredoxin were increased in patients with
      hepatocellular carcinoma (HCC). The optimum diagnostic cutoff for thioredoxin was
      20.5 ng/mL (area under curve [AUC] 0.946 [95% CI 0.923-0.969] in the training
      cohort; 0.941 [0.918-0.963] in the validation cohort). High serum concentrations
      of thioredoxin differentiated HCC from chronic liver diseases and cirrhosis
      (0.901 [0.875-0.923] in the training cohort; 0.906 [0.870-0.925] in the
      validation cohort). Furthermore, a higher proportion of patients with very early
      HCC had positive results for thioredoxin than for alpha-Fetoprotein (AFP) (73.7%
      VS.31.6%; P < 0.0001). Among AFP-negative patients with very early HCC, 18
      (69.2%) of 26 had positive thioredoxin results. Our results indicate that serum
      thioredoxin complements measurement of AFP in the diagnosis of HCC, especially in
      very early disease. Combined model (thioredoxin and AFP) showed a significantly
      greater discriminatory ability as compared with those markers alone. 

PMID- 25871388
TI  - IL-8 confers resistance to EGFR inhibitors by inducing stem cell properties in
      lung cancer.
AB  - Epidermal growth factor receptor (EGFR)-targeted strategy is limited by
      resistance. We identify the potential genes involved in EGFR TKI (tyrosine kinase
      inhibitor) resistance and study the therapeutic mechanism in the non-small cell
      lung cancers. Potential genes involved in resistance were examined by analyzing
      datasets from a pair of EGFR TKI-sensitive (PC9) and TKI-resistant cells
      (PC9/gef). Blood specimens from patients taking EGFR TKI as first-line treatment
      were used to examine the correlation between drug's efficacy and IL-8 level. The
      effects of IL-8 on gefitinib-induced apoptosis, stemness, and in vivo
      tumorigenicity were investigated using established cell lines. We identified IL-8
      was up-regulated in gefitinib-resistant cells, and high plasma IL-8 level was
      correlated with shorter progression-free-survival time. IL-8 overexpression
      suppressed gefitinib-induced apoptosis in gefitinib-sensitive cells. By contrast,
      suppression of IL-8 enhanced gefitinib-induced cell death in gefitinib-resistant
      cells. IL-8 also increased stem-like characteristics including aldehyde
      dehydrogenase activity, expression of stemness-related genes, clonogenic
      activity, side-population, and in vivo tumorigenicity. Consistently, knockdown of
      IL-8 leads to loss of stem cell-like characteristics in gefitinib-resistant
      cells. Our study demonstrates an important role for IL-8, and suggests IL-8 is a
      potential therapeutic target for overcoming EGFR TKI resistance. 

PMID- 25871389
TI  - Sortilin is associated with breast cancer aggressiveness and contributes to tumor
      cell adhesion and invasion.
AB  - The neuronal membrane protein sortilin has been reported in a few cancer cell
      lines, but its expression and impact in human tumors is unclear. In this study,
      sortilin was analyzed by immunohistochemistry in a series of 318 clinically
      annotated breast cancers and 53 normal breast tissues. Sortilin was detected in
      epithelial cells, with increased levels in cancers, as compared to normal tissues
      (p = 0.0088). It was found in 79% of invasive ductal carcinomas and 54% of
      invasive lobular carcinomas (p < 0.0001). There was an association between
      sortilin expression and lymph node involvement (p = 0.0093), suggesting a
      relationship with metastatic potential. In cell culture, sortilin levels were
      higher in cancer cell lines compared to non-tumorigenic breast epithelial cells
      and siRNA knockdown of sortilin inhibited cancer cell adhesion, while
      proliferation and apoptosis were not affected. Breast cancer cell migration and
      invasion were also inhibited by sortilin knockdown, with a decrease in focal
      adhesion kinase and SRC phosphorylation. In conclusion, sortilin participates in
      breast tumor aggressiveness and may constitute a new therapeutic target against
      tumor cell invasion. 

PMID- 25871390
TI  - Loss of Cbl and Cbl-b ubiquitin ligases abrogates hematopoietic stem cell
      quiescence and sensitizes leukemic disease to chemotherapy.
AB  - Cbl and Cbl-b are tyrosine kinase-directed RING finger type ubiquitin ligases
      (E3s) that negatively regulate cellular activation pathways. E3 activity
      disrupting human Cbl mutations are associated with myeloproliferative disorders
      (MPD) that are reproduced in mice with Cbl RING finger mutant knock-in or
      hematopoietic Cbl and Cbl-b double knockout. However, the role of Cbl proteins in
      hematopoietic stem cell (HSC) homeostasis, especially in the context of MPD is
      unclear. Here we demonstrate that HSC expansion and MPD development upon combined
      Cbl and Cbl-b deletion are dependent on HSCs. Cell cycle analysis demonstrated
      that DKO HSCs exhibit reduced quiescence associated with compromised
      reconstitution ability and propensity to undergo exhaustion. We show that
      sustained c-Kit and FLT3 signaling in DKO HSCs promotes loss of colony-forming
      potential, and c-Kit or FLT3 inhibition in vitro protects HSCs from exhaustion.
      In vivo, treatment with 5-fluorouracil hastens DKO HSC exhaustion and protects
      mice from death due to MPD. Our data reveal a novel and leukemia therapy-relevant
      role of Cbl and Cbl-b in the maintenance of HSC quiescence and protection against
      exhaustion, through negative regulation of tyrosine kinase-coupled receptor
      signaling. 

PMID- 25871391
TI  - XPC inhibits NSCLC cell proliferation and migration by enhancing E-Cadherin
      expression.
AB  - Xeroderma pigmentosum complementation group C (XPC) protein is an important DNA
      damage recognition factor in nucleotide excision repair. Deletion of XPC is
      associated with early stages of human lung carcinogenesis, and reduced XPC mRNA
      levels predict poor patient outcome for non-small cell lung cancer (NSCLC).
      However, the mechanisms linking loss of XPC expression and poor prognosis in lung
      cancer are still unclear. Here, we report evidence that XPC silencing drives
      proliferation and migration of NSCLC cells by down-regulating E-Cadherin. XPC
      knockdown enhanced proliferation and migration while decreasing E-Cadherin
      expression in NSCLC cells with an epithelial phenotype. Restoration of E-Cadherin
      in these cells suppressed XPC knockdown-induced cell growth both in vitro and in
      vivo. Mechanistic studies showed that the loss of XPC repressed E-Cadherin
      expression by activating the ERK pathway and upregulating Snail expression. Our
      findings indicate that XPC silencing-induced reduction of E-Cadherin expression
      contributes, at least in part, to the poor outcome of NSCLC patients with low XPC
      expression. 

PMID- 25871392
TI  - CD163+ tumor-associated macrophage is a prognostic biomarker and is associated
      with therapeutic effect on malignant pleural effusion of lung cancer patients.
AB  - CD163+ tumor-associated macrophages (TAMs) play an important role in the
      progression of cancer. However, the significance of CD163+ TAMs in malignant
      pleural effusion (MPE) is still unclear. The aim of this study is to evaluate the
      prognostic value of CD163+ TAMs in MPE, and the regulatory effect of an immune
      adjuvant (pseudomonas aeruginosa - mannose-sensitive hemagglutinin, PA-MSHA,
      which is used for MPE treatment in clinic) on CD163+ TAMs in MPE. Here, we found
      that the percentage of CD163+ TAMs in MPE was significantly higher than that in
      non-malignant pleural effusion (P<0.001). More importantly, CD163+ TAMs in MPE
      patients were an independent prognostic factor for progression-free survival. M2
      related cytokines were highly expressed in MPE-derived CD163+ TAMs than in MPE
      derived CD163- macrophages (P<0.05). CD163+ TAMs frequency in MPE patients was
      obviously reduced after PA-MSHA treatment in clinic (P<0.05). After treatment
      with PA-MSHA, M2 macrophages were re-educated to M1 macrophages in vitro. TLR4
      blocking antibody inhibited M2 macrophages polarization to M1 macrophages induced
      by PA-MSHA. These findings highlight that accumulation of CD163+ TAMs in MPE
      caused by lung cancer is closely correlated with poor prognosis. CD163+ TAMs are
      associated with therapeutic effect in MPE. PA-MSHA re-educates CD163+ TAMs to M1
      macrophages through TLR4-mediated pathway in MPE. 

PMID- 25871393
TI  - Independent replication of a melanoma subtype gene signature and evaluation of
      its prognostic value and biological correlates in a population cohort.
AB  - Development and validation of robust molecular biomarkers has so far been limited
      in melanoma research. In this paper we used a large population-based cohort to
      replicate two published gene signatures for melanoma classification. We assessed
      the signatures prognostic value and explored their biological significance by
      correlating them with factors known to be associated with survival (vitamin D) or
      etiological routes (nevi, sun sensitivity and telomere length). Genomewide
      microarray gene expressions were profiled in 300 archived tumors (224 primaries,
      76 secondaries). The two gene signatures classified up to 96% of our samples and
      showed strong correlation with melanoma specific survival (P=3 x 10(-4)), Breslow
      thickness (P=5 x 10(-10)), ulceration (P=9.x10-8) and mitotic rate (P=3 x 10(
      7)), adding prognostic value over AJCC stage (adjusted hazard ratio 1.79, 95%CI
      1.13-2.83), as previously reported. Furthermore, molecular subtypes were
      associated with season-adjusted serum vitamin D at diagnosis (P=0.04) and
      genetically predicted telomere length (P=0.03). Specifically, molecular high
      grade tumors were more frequent in patients with lower vitamin D levels whereas
      high immune tumors came from patients with predicted shorter telomeres. Our data
      confirm the utility of molecular biomarkers in melanoma prognostic estimation
      using tiny archived specimens and shed light on biological mechanisms likely to
      impact on cancer initiation and progression.

PMID- 25871394
TI  - Molecular profiling of peripheral blood is associated with circulating tumor
      cells content and poor survival in metastatic castration-resistant prostate
      cancer.
AB  - The enumeration of circulating tumor cells (CTCs) in peripheral blood correlates
      with clinical outcome in castration-resistant prostate cancer (CRPC). We analyzed
      the molecular profiling of peripheral blood from 43 metastatic CRPC patients with
      known CTC content in order to identify genes that may be related to prostate
      cancer progression. Global gene expression analysis identified the differential
      expression of 282 genes between samples with >=5 CTCs vs <5 CTCs, 58.6% of which
      were previously described as over-expressed in prostate cancer (18.9% in primary
      tumors and 56.1% in metastasis). Those genes were involved in survival functions
      such as metabolism, signal transduction, gene expression, cell growth, death, and
      movement. The expression of selected genes was evaluated by quantitative RT-PCR.
      This analysis revealed a two-gene model (SELENBP1 and MMP9) with a high
      significant prognostic ability (HR 6; 95% CI 2.61 - 13.79; P<0.0001). The
      combination of the two-gene signature plus the CTCs count showed a higher
      prognostic ability than CTCs enumeration or gene expression alone (P<0.05). This
      study shows a gene expression profile in PBMNC associated with CTCs count and
      clinical outcome in metastatic CRPC, describing genes and pathways potentially
      associated with CRPC progression. 

PMID- 25871395
TI  - Targeted therapy of glioblastoma stem-like cells and tumor non-stem cells using
      cetuximab-conjugated iron-oxide nanoparticles.
AB  - Malignant gliomas remain aggressive and lethal primary brain tumors in adults.
      The epidermal growth factor receptor (EGFR) is frequently overexpressed in the
      most common malignant glioma, glioblastoma (GBM), and represents an important
      therapeutic target. GBM stem-like cells (GSCs) present in tumors are felt to be
      highly tumorigenic and responsible for tumor recurrence. Multifunctional magnetic
      iron-oxide nanoparticles (IONPs) can be directly imaged by magnetic resonance
      imaging (MRI) and designed to therapeutically target cancer cells. The targeting
      effects of IONPs conjugated to the EGFR inhibitor, cetuximab (cetuximab-IONPs),
      were determined with EGFR- and EGFRvIII-expressing human GBM neurospheres and
      GSCs. Transmission electron microscopy revealed cetuximab-IONP GBM cell binding
      and internalization. Fluorescence microscopy and Prussian blue staining showed
      increased uptake of cetuximab-IONPs by EGFR- as well as EGFRvIII-expressing GSCs
      and neurospheres in comparison to cetuximab or free IONPs. Treatment with
      cetuximab-IONPs resulted in a significant antitumor effect that was greater than
      with cetuximab alone due to more efficient, CD133-independent cellular targeting
      and uptake, EGFR signaling alterations, EGFR internalization, and apoptosis
      induction in EGFR-expressing GSCs and neurospheres. A significant increase in
      survival was found after cetuximab-IONP convection-enhanced delivery treatment of
      3 intracranial rodent GBM models employing human EGFR-expressing GBM xenografts. 

PMID- 25871396
TI  - Anterior gradient protein 2 expression in high grade head and neck squamous cell
      carcinoma correlated with cancer stem cell and epithelial mesenchymal transition.
AB  - Anterior gradient protein 2 (AGR2) is a novel biomarker with potential oncogenic
      role. We sought to investigate the diagnostic and prognostic role of AGR2 on head
      and neck squamous cell carcinoma (HNSCC) with an emphasis on its correlation of
      cancer stemloid cells (CSC) and epithelial mesenchymal transition (EMT). We found
      that AGR2 protein levels were higher in HNSCC than in normal oral mucosa. High
      levels of AGR2 were associated with the T category, pathological grade and lymph
      node metastasis of HNSCC. Expression of AGR2 increased in recurring HNSCC after
      radiotherapy and in post cisplatin-based chemotherapeutic tissues. In HNSCC cell
      lines, knock-down of AGR2 induced apoptosis, reduced sphere formation, and down
      regulated Survivin, Cyclin D1, Bcl2, Bcl2l1, Slug, Snail, Nanog and Oct4. In
      addition, over-expressed AGR2 in transgenic mice with spontaneous HNSCC was
      associated with lost function of Tgfbr1 and/ or lost function of Pten. In vitro
      knockdown TGFBR1 in HNSCC cell lines increased AGR2 expression. These results
      suggest that AGR2 is involved in EMT and self-renewal of CSC and may present a
      potential therapeutic target (oncotarget) for HNSCC. 

PMID- 25871397
TI  - MiR-203 downregulation is responsible for chemoresistance in human glioblastoma
      by promoting epithelial-mesenchymal transition via SNAI2.
AB  - Epithelial-mesenchymal transition (EMT) has been recognized as a key element of
      cell migration, invasion, and drug resistance in several types of cancer. In this
      study, our aim was to clarify microRNAs (miRNAs)-related mechanisms underlying
      EMT followed by acquired resistance to chemotherapy in glioblastoma (GBM). We
      used multiple methods to achieve our goal including microarray analysis, qRT-PCR,
      western blotting analysis, loss/gain-of-function analysis, luciferase assays,
      drug sensitivity assays, wound-healing assay and invasion assay. We found that
      miR-203 expression was significantly lower in imatinib-resistant GBM cells
      (U251AR, U87AR) that underwent EMT than in their parental cells (U251, U87).
      Ectopic expression of miR-203 with miRNA mimics effectively reversed EMT in
      U251AR and U87AR cells, and sensitized them to chemotherapy, whereas inhibition
      of miR-203 in the sensitive lines with antisense oligonucleotides induced EMT and
      conferred chemoresistance. SNAI2 was identified as a direct target gene of miR
      203. The knockdown of SNAI2 by short hairpin RNA (shRNA) inhibited EMT and drug
      resistance. In GBM patients, miR-203 expression was inversely related to SNAI2
      expression, and those tumors with low expression of miR-203 experienced poorer
      clinical outcomes. Our findings indicate that re-expression of miR-203 or
      targeting SNAI2 might serve as potential therapeutic approaches to overcome
      chemotherapy resistance in GBM. 

PMID- 25871398
TI  - MPGES-1-derived PGE2 suppresses CD80 expression on tumor-associated phagocytes to
      inhibit anti-tumor immune responses in breast cancer.
AB  - Prostaglandin E2 (PGE2) favors multiple aspects of tumor development and immune
      evasion. Therefore, microsomal prostaglandin E synthase (mPGES-1/-2), is a
      potential target for cancer therapy. We explored whether inhibiting mPGES-1 in
      human and mouse models of breast cancer affects tumor-associated immunity. A new
      model of breast tumor spheroid killing by human PBMCs was developed. In this
      model, tumor killing required CD80 expression by tumor-associated phagocytes to
      trigger cytotoxic T cell activation. Pharmacological mPGES-1 inhibition increased
      CD80 expression, whereas addition of PGE2, a prostaglandin E2 receptor 2 (EP2)
      agonist, or activation of signaling downstream of EP2 reduced CD80 expression.
      Genetic ablation of mPGES-1 resulted in markedly reduced tumor growth in PyMT
      mice. Macrophages of mPGES-1(-/-) PyMT mice indeed expressed elevated levels of
      CD80 compared to their wildtype counterparts. CD80 expression in tumor-spheroid
      infiltrating mPGES-1(-/-) macrophages translated into antigen-specific cytotoxic
      T cell activation. In conclusion, mPGES-1 inhibition elevates CD80 expression by
      tumor-associated phagocytes to restrict tumor growth. We propose that mPGES-1
      inhibition in combination with immune cell activation might be part of a
      therapeutic strategy to overcome the immunosuppressive tumor microenvironment.

PMID- 25871399
TI  - Chorein addiction in VPS13A overexpressing rhabdomyosarcoma cells.
AB  - Chorein encoded by VPS13A (vacuolar protein sorting-associated protein 13A) is
      defective in chorea-acanthocytosis. Chorein fosters neuronal cell survival,
      cortical actin polymerization and cell stiffness. In view of its anti-apoptotic
      effect in neurons, we explored whether chorein is expressed in cancer cells and
      influences cancer cell survival. RT-PCR was employed to determine transcript
      levels, specific siRNA to silence chorein, FACS analysis to follow apoptosis and
      Western blotting to quantify protein abundance. Chorein transcripts were detected
      in various cancer cell types. The mRNA coding for chorein and chorein protein
      were most abundant in drug resistant, poorly differentiated human
      rhabdomyosarcoma cells. Chorein silencing significantly reduced the ratio of
      phosphorylated (and thus activated) to total phosphoinositide 3 kinase (PI-3K),
      pointing to inactivation of this crucial pro-survival signaling molecule.
      Moreover, chorein silencing diminished transcript levels and protein expression
      of anti-apoptotic BCL-2 and enhanced transcript levels of pro-apoptotic Bax.
      Silencing of chorein in rhabdomyosarcoma cells was followed by mitochondrial
      depolarization, caspase 3 activation and stimulation of early and late apoptosis.
      In conclusion, chorein is expressed in various cancer cells. In cells with high
      chorein expression levels chorein silencing promotes apoptotic cell death, an
      effect paralleled by down-regulation of PI-3K activity and BCL-2/Bax expression
      ratio. 

PMID- 25871400
TI  - Salinomycin decreases doxorubicin resistance in hepatocellular carcinoma cells by
      inhibiting the beta-catenin/TCF complex association via FOXO3a activation.
AB  - Doxorubicin is a conventional and effective chemotherapy drug against
      hepatocellular carcinoma (HCC). However, during long-term doxorubicin
      monotherapy, HCC cells may eventually develop acquired-resistance to doxorubicin
      which results in recurrence and a poor prognosis. Salinomycin, an ionophore
      antibiotic, was recently reported to selectively kill human cancer stem cells
      (CSCs) which were response for chemoresistance. In this study, salinomycin was
      found to exert synergistic cytotoxicity with doxorubicin in HCC cells and be
      capable of inhibiting doxorubicin-induced epithelial-mesenchymal transition
      (EMT), an important cellular process involved in the acquired chemoresistance of
      tumors. Further experiments revealed that FOXO3a, a multifunctional transcription
      factor that can be activated by salinomycin, was vital in mediating doxorubicin
      induced EMT. In addition, activated FOXO3a disturbed the interaction between beta
      catenin and TCF and inhibited the expression of beta-catenin/TCF target genes
      (ZEB1, c-Myc and CyclinD1), which played important roles in doxorubicin-induced
      EMT in HCC cells. Finally, the enhanced curative efficacy of combination
      treatment of doxorubicin and salinomycin for HCC was confirmed in established
      xenograft models. In summary, the present study identifies a new doxorubicin
      based chemotherapy for advanced HCC and provides a potential anti-cancer strategy
      targeting FOXO3a and related cell pathway molecules. 

PMID- 25871401
TI  - Inhibition of the HER2-YB1-AR axis with Lapatinib synergistically enhances
      Enzalutamide anti-tumor efficacy in castration resistant prostate cancer.
AB  - Incurable castration-resistant prostate cancer (CRPC) is driven by androgen
      receptor (AR) activation. Potent therapies that prevent AR signaling, such as
      Enzalutamide (ENZ), are mainstay treatments for CRPC; however patients eventually
      progress with ENZ resistant (ENZR) disease. In this study, we investigated one
      mechanism of ENZ resistance, and tried to improve therapeutic efficiency of ENZ.
      We found HER2 expression is increased in ENZR tumors and cell lines, and is
      induced by ENZ treatment of LNCaP cells. ENZ-induced HER2 overexpression was
      dependent on AKT-YB1 activation and modulated AR activity. HER2 dependent AR
      activation in LNCaP and ENZR cells was effectively blocked by treatment with the
      EGFR/HER2 inhibitor Lapatinib, which reduced cell viability and increased
      apoptosis. Despite efficacy in vitro, in vivo monotherapy with Lapatinib did not
      prevent ENZR tumor growth. However, combination treatment of Lapatinib with ENZ
      most effectively induced cell death in LNCaP cells in vitro and was more
      effective than ENZ alone in preventing tumor growth in an in vivo model of CRPC.
      These results suggest that while HER2 overexpression and subsequent AR activation
      is a targetable mechanism of resistance to ENZ, therapy using Lapatinib is only a
      rational therapeutic approach when used in combination with ENZ in CRPC. 

PMID- 25871402
TI  - Experimental microembolism induces localized neuritic pathology in guinea pig
      cerebrum.
AB  - Microbleeds are a common finding in aged human brains. In Alzheimer's disease
      (AD), neuritic plaques composed of beta-amyloid (Abeta) deposits and dystrophic
      neurites occur frequently around cerebral vasculature, raising a compelling
      question as to whether, and if so, how, microvascular abnormality and
      amyloid/neuritic pathology might be causally related. Here we used a guinea pig
      model of cerebral microembolism to explore a potential inductive effect of
      vascular injury on neuritic and amyloid pathogenesis. Brains were examined 7-30
      days after experimental microvascular embolization occupying ~0.5% of total
      cortical area. Compared to sham-operated controls, glial fibrillary acidic
      protein immunoreactivity was increased in the embolized cerebrum, evidently
      around intracortical vasculature. Swollen/sprouting neurites exhibiting increased
      reactivity of nicotinamide adenine dinucleotide phosphate diaphorase,
      parvalbumin, vesicular glutamate transporter 1 and choline acetyltransferase
      appeared locally in the embolized brains in proximity to intracortical
      vasculature. The embolization-induced swollen/sprouting neurites were also
      robustly immunoreactive for beta-amyloid precursor protein and beta-secretase-1,
      the substrate and initiating enzyme for Abeta genesis. These experimental data
      suggest that microvascular injury can induce multisystem neuritic pathology
      associated with an enhanced amyloidogenic potential in wild-type mammalian brain.

PMID- 25871403
TI  - Discontinuous versus Continuous Weaning in Stroke Patients.
AB  - BACKGROUND: An increasing number of stroke patients have to be supported by
      mechanical ventilation in intensive care units (ICU), with a relevant proportion
      of them requiring gradual withdrawal from a respirator. To date, weaning studies
      have focused merely on mixed patient groups, COPD patients or patients after
      cardiac surgery. Therefore, the best weaning strategy for stroke patients remains
      to be determined. METHODS: Here, we designed a prospective randomized controlled
      study comparing adaptive support ventilation (ASV), a continuous weaning
      strategy, with biphasic positive airway pressure (BIPAP) in combination with
      spontaneous breathing trials, a discontinuous technique, in the treatment of
      stroke patients. The primary endpoint was the duration of the weaning process.
      RESULTS: Only the 40 (out of 54) patients failing in an initial spontaneous
      breathing trial (T-piece test) were included into the study; the failure
      proportion is considerably larger compared to previous studies. Eligible patients
      were pseudo-randomly assigned to one of the two weaning groups. Both groups did
      not differ regarding age, gender, and severity of stroke. The results showed that
      the median weaning duration was 10.7 days (+/-SD 7.0) in the discontinuous
      weaning group, and 8 days (+/-SD 4.5) in the continuous weaning group (p < 0.05).
      CONCLUSIONS: To the best of our knowledge, this is the first clinical study to
      show that continuous weaning is significantly more effective compared to
      discontinuous weaning in mechanically ventilated stroke patients. We suppose that
      the reason for the superiority of continuous weaning using ASV as well as the bad
      performance of our patients in the 2 h T-piece test is caused by the patients'
      compliance. Compared to patients on surgical and medical ICUs, neurological
      patients more often suffer from reduced vigilance, lack of adverse-effects
      reflexes, dysphagia, and cerebral dysfunction. Therefore, stroke patients may
      profit from a more gradual withdrawal of weaning.

PMID- 25871404
TI  - Drug-induced ocular adverse reactions: review of the safety alerts issued during
      the last decade.
AB  - PURPOSE: The purpose of this study was to evaluate ocular-related adverse events
      associated with the use of drugs by analyzing the content of safety alerts issued
      by major regulatory authorities during the last decade. METHODS: The websites of
      4 health regulatory authorities were reviewed to identify safety alerts issued on
      ocular adverse events. Safety alerts were included if they have been issued
      between January 2005 and December 2014. Only safety alerts on drugs with market
      authorization were considered for inclusion. RESULTS: Thirty-eight safety alerts
      were included in the study. Urologicals (n = 11; 29%), followed by drugs used in
      diabetes, antibacterials for systemic use, antineoplastic agents, and
      ophthalmologicals were the most frequently suspected drugs evaluated in the
      safety alerts (n = 4; 10%, each). The most frequently evaluated adverse events
      were visual disorders NEC (n = 12; 32%), including visual impairment, diplopia,
      and blurred vision. The majority (n = 25; 66%) of the safety alerts were
      supported by postmarketing spontaneous reports. The most commonly updated drug
      label section was the Warnings and Precautions section (n = 33; 87%), followed by
      the Adverse Reactions section (n = 26; 68%). CONCLUSIONS: Ocular adverse events,
      newly identified during this decade, come mostly from systemic drugs, some of
      them marketed for several years. Physicians should be aware of drug-induced
      adverse events in the eye to avoid, as soon as possible, their progression, which
      can lead to visual impairment.

PMID- 25871405
TI  - A Highly Characterized Yeast Toolkit for Modular, Multipart Assembly.
AB  - Saccharomyces cerevisiae is an increasingly attractive host for synthetic biology
      because of its long history in industrial fermentations. However, until recently,
      most synthetic biology systems have focused on bacteria. While there is a wealth
      of resources and literature about the biology of yeast, it can be daunting to
      navigate and extract the tools needed for engineering applications. Here we
      present a versatile engineering platform for yeast, which contains both a rapid,
      modular assembly method and a basic set of characterized parts. This platform
      provides a framework in which to create new designs, as well as data on
      promoters, terminators, degradation tags, and copy number to inform those
      designs. Additionally, we describe genome-editing tools for making modifications
      directly to the yeast chromosomes, which we find preferable to plasmids due to
      reduced variability in expression. With this toolkit, we strive to simplify the
      process of engineering yeast by standardizing the physical manipulations and
      suggesting best practices that together will enable more straightforward
      translation of materials and data from one group to another. Additionally, by
      relieving researchers of the burden of technical details, they can focus on
      higher-level aspects of experimental design. 

PMID- 25871406
TI  - Sensitization of an endogenous photosensitizer: electronic spectroscopy of
      riboflavin in the proximity of semiconductor, insulator, and metal nanoparticles.
AB  - Riboflavin (Rf) is a class of important vitamins (Vitamin B2) and a well-known
      antioxidant. Here we have synthesized nanohybrids of Rf with a number of
      inorganic nanoparticles (NPs); namely zinc oxide (ZnO), titanium oxide (TiO2),
      aluminum oxide (Al2O3) and gold NPs of similar sizes. While high resolution
      transmission electron microscopy (HRTEM) confirms integrity and sizes of the NPs,
      intactness of the molecular structure of the drug Rf is revealed from absorption
      and steady-state emission spectra of the drug in the nanohybrid. Raman
      spectroscopy on the nanohybrids shows the nature of molecular complexation of the
      drug with the inorganic NPs. For the semiconductor and insulator NPs, the
      complexation is found to be noncovalent, however, a covalent attachment of the
      drug with the dangling bonds of metal atoms at the surface is observed. In order
      to investigate antioxidant activity of the nanohybrids, we have performed 2, 2
      diphenyl-1-picrylhydrazyl (DPPH) assay of the nanohybrids in dark as well as
      under blue light irradiation. Whereas change of the antioxidant activity of the
      nanohybrids with respect to free riboflavin in the absence of light is observed
      to be insignificant, a drastic change in the activity in the case of TiO2 and ZnO
      in the presence of light is evident. No change in the case of Al2O3 and a
      significant decrease in the antioxidant activity for gold nanohybrids are also
      remarkable. Picosecond-resolved fluorescence studies on the nanohybrids reveal a
      molecular picture of the differential antioxidant activities. An ultrafast
      photoinduced electron transfer from Rf to ZnO and TiO2 are clearly evident from
      the corresponding fluorescence transients. We have compared the picosecond
      resolved transients with that of Rf in the presence of a well-known electron
      acceptor benzoquinone (BQ) and found similar time scales. No temporal change in
      the fluorescence transient of riboflavin in Al2O3 nanohybrids compared to that of
      free Rf is observed indicating uneventful excited state relaxation of the
      nanohybrids. Nanosurface energy transfer (NSET) over Forster resonance energy
      transfer (FRET) is found to be the prevailing de-excitation mechanism in the case
      of gold nanohybrids, because of the strong spectral overlap between Rf emission
      and surface plasmon absorption of the gold NPs. Different excited state
      mechanisms as revealed from our studies are expected to be useful for the design
      of NP-sensitized drugs, which are reported sparsely in the literature. 

PMID- 25871407
TI  - Rituximab as consolidation therapy did not improve outcome in patients with
      diffuse large B-cell lymphoma at complete response after dose-dense chemotherapy
      (CHOP-14).
AB  - The authors started a clinical trial to assess the efficacy and toxicity of
      rituximab (R) as consolidation in patients with diffuse large B-cell lymphoma,
      with poor prognostic factors, who were in complete response (CR) after dose-dense
      chemotherapy (CHOP-14). Four hundred sixty-five untreated patients, with advanced
      stages (III and IV), older (median age >60 years old), and high clinical risk,
      were treated with dose-dense CHOP-14 (cyclophosphamide 1500 mg/m(2), i.v., day 1;
      vincristine 2 mg, i.v., standard dose, day 1; epirubicin 120 mg/m(2), i.v., day
      1; and prednisone 60 mg/m(2), p.o., days 1-5) every 14 days for six cycles. If CR
      was achieved, the patients were allocated to receive R (375 mg/m(2), days 1, 8,
      15, and 22) at 3 and 9 months after chemotherapy. Three hundred twenty-five
      patients achieved CR (70%) and were allocated to receive R (151 patients) or not
      (174 patients). Actuarial curves at 5 years showed that progression-free survival
      (PFS) was 51% (95% confidence interval [CI]: 44%-58%) in the R group and 53% (95%
      CI: 47%-59%) in the observation group (p=0.8). Overall survival (OS) was 65% (95%
      CI: 58%-71%) and 66% (95% CI: 59%-72%), respectively (p=0.78). Late toxicities
      were more frequent in the R group. The authors showed that the use of R as a
      consolidation treatment was not useful to improve PFS and OS and toxicity
      secondary to R was frequent. They did not recommend the use of R as consolidation
      in this patient setting. 

PMID- 25871408
TI  - Low-Frequency Electromagnetic Field Exposure Enhances Extracellular Trap
      Formation by Human Neutrophils through the NADPH Pathway.
AB  - Low-frequency (LF) electromagnetic fields (EMFs) are abundantly present in modern
      society, and the potential biological consequences of exposure to these fields
      are under intense debate. Immune cells are suggested as possible target cells,
      though a clear mechanism is lacking. Considering their crucial role in innate
      immune activation, we selected an ex vivo exposure set-up with human neutrophils
      to investigate a possible correlation between neutrophil extracellular trap (NET)
      formation and LF EMF exposure. Our study shows that formation of NETs is enhanced
      by LF EMF exposure. Enhanced NET formation leads to increased antimicrobial
      properties as well as damage to surrounding cells. We found that LF-EMF-induced
      NET formation is dependent on the NADPH oxidase pathway and production of
      reactive oxygen species. Additionally, LF EMF exposure does not influence
      autophagy and PAD4 activity. Our study provides a mechanism by which exposure to
      LF EMFs could influence the innate immune system. 

PMID- 25871410
TI  - Hyaluronic Acid Based Hydrogels Attenuate Inflammatory Receptors and
      Neurotrophins in Interleukin-1beta Induced Inflammation Model of Nucleus Pulposus
      Cells.
AB  - Inflammation plays an important role in symptomatic intervertebral disc
      degeneration and is associated with the production of neurotrophins in
      sensitizing innervation into the disc. The use of high molecular weight (HMw)
      hyaluronic acid (HA) hydrogels offers a potential therapeutic biomaterial for
      nucleus pulposus (NP) regeneration as it exerts an anti-inflammatory effect and
      provides a microenvironment that is more suitable for NP. Therefore, it was
      hypothesized that cross-linked HMw HA hydrogels modulate the inflammatory
      receptor of IL-1R1, MyD88 and neurotrophin expression of nerve growth factor
      (NGF) and brain-derived neurotrophic factor (BDNF) in an in vitro inflammation
      model of NP. HA cross-linking was optimized using various concentrations of 4-arm
      PEG-amine by determination of free carboxyl groups of HA and unreacted free amine
      groups of PEG-amine. The optimally cross-linked HA hydrogels were characterized
      for hydrolytic stability, enzymatic degradation and cytotoxicity on NP cells. The
      therapeutic effect of HA hydrogels was further investigated in IL-1beta induced
      inflammation on NP cell cultures and the mechanism of HA by examining the
      expression of cell surface receptor of CD44. Hydrogel was optimally cross-linked
      at 75 mM PEG, stable in phosphate buffered saline, and showed greater than 40%
      resistance to enzymatic degradation. No cytotoxic effect of NP cells was observed
      in the presence of hydrogels for 1, 3, and 7 days. IL-1R1 and MyD88 were
      significantly suppressed. Additionally, NGF and BDNF mRNA were down-regulated
      after treatment with cross-linked HA hydrogel. Possible protective mechanism of
      HA is shown by high expression of CD44 receptor of NP cells after HA treatment in
      which suggest the binding of HA to CD44 receptor and prevent NP cells from
      further undergoing inflammation. These results indicate that optimally stabilized
      cross-linked HMw HA hydrogel has a therapeutic effect in response to inflammation
      associated pain and becomes an ideal matrices hydrogel for NP regeneration. 

PMID- 25871411
TI  - Carcinoid Heart Disease: From Pathophysiology to Treatment--'Something in the Way
      It Moves'.
AB  - Carcinoid heart disease (CHD) is a rare cardiac manifestation occurring in
      patients with advanced neuroendocrine tumours and the carcinoid syndrome, usually
      involving the right-sided heart valves and eventually leading to right heart
      failure. The pathophysiology of CHD is still obscure and believed to be
      multifactorial, as a variety of vasoactive substances secreted by the tumour
      appear to be involved. The management of patients with CHD is complex, as both
      the systemic malignant disease and the heart involvement have to be addressed.
      Timely diagnosis and early surgical treatment in appropriately selected patients
      are of outmost importance, as CHD is associated with increased morbidity and
      mortality. Valve replacement surgery alleviates right heart failure and may also
      contribute to improved survival. In the present study we have comprehensively
      reviewed the existing literature to date, mainly focusing on the pathophysiology
      of CHD. Other aspects of CHD (such as the clinical presentation, diagnostic tools
      and therapeutic approach) are addressed in brief.

PMID- 25871409
TI  - Socioeconomic Status and Neuropsychological Functioning: Associations in an
      Ethnically Diverse HIV+ Cohort.
AB  - OBJECTIVE: There is limited research examining the relationship between
      socioeconomic status (SES) and neuropsychological functioning, particularly in
      racial/ethnic minority and HIV+ populations. However, there are complex
      associations between poverty, education, HIV disease, race/ethnicity, and health
      outcomes in the US. METHOD: We explored these relationships among an ethnically
      diverse sample of 134 HIV+ adults using a standardized SES measure (i.e., the
      Hollingshead scale), a comprehensive NP test battery, and a functional evaluation
      (i.e., Patient's Assessment of Own Functioning Inventory and Modified
      Instrumental Activities of Daily Living Scale). RESULTS: Bivariate analyses
      showed that adult SES was significantly, positively correlated with
      neuropsychological performance on specific tests within the domains of verbal
      fluency, attention/concentration, learning, memory, processing speed, and
      executive functioning, and childhood SES was significantly linked to measures of
      verbal fluency, processing speed, and executive functioning. In a series of
      linear regressions, controlling for SES significantly attenuated group
      differences in NP test scores between racial/ethnic minority individuals and non
      Hispanic White individuals. Finally, SES scores significantly differed across HIV
      Associated Neurocognitive Disorder (HAND) diagnoses. In a binary logistic
      regression, SES was the only independent predictor of HAND diagnosis.
      CONCLUSIONS: HIV+ individuals with lower SES may be more vulnerable to HIV
      associated neuropsychological sequelae due to prominent health disparities,
      although the degree to which this is influenced by factors such as test bias
      remains unclear. Overall, our results suggest that SES is significantly linked to
      neuropsychological test performance in HIV+ individuals, and is an important
      factor to consider in clinical practice.

PMID- 25871412
TI  - Future and past of preventive dentistry. Preface.

PMID- 25871413
TI  - Models and role models.
AB  - Developing experimental models to understand dental caries has been the theme in
      our research group. Our first, the pH-cycling model, was developed to investigate
      the chemical reactions in enamel or dentine, which lead to dental caries. It
      aimed to leverage our understanding of the fluoride mode of action and was also
      utilized for the formulation of oral care products. In addition, we made use of
      intra-oral (in situ) models to study other features of the oral environment that
      drive the de/remineralization balance in individual patients. This model
      addressed basic questions, such as how enamel and dentine are affected by
      challenges in the oral cavity, as well as practical issues related to fluoride
      toothpaste efficacy. The observation that perhaps fluoride is not sufficiently
      potent to reduce dental caries in the present-day society triggered us to expand
      our knowledge in the bacterial aetiology of dental caries. For this we developed
      the Amsterdam Active Attachment biofilm model. Different from studies on
      planktonic ('single') bacteria, this biofilm model captures bacteria in a habitat
      similar to dental plaque. With data from the combination of these models, it
      should be possible to study separate processes which together may lead to dental
      caries. Also products and novel agents could be evaluated that interfere with
      either of the processes. Having these separate models in place, a suggestion is
      made to design computer models to encompass the available information. Models but
      also role models are of the utmost importance in bringing and guiding research
      and researchers.

PMID- 25871414
TI  - Noninvasive dentistry: a dream or reality?
AB  - Various caries prevention and repair strategies are reviewed in this article
      ranging from the use of fluoride to nanohydroxyapatite particles. Several of the
      strategies which combine fluoride and calcium and phosphate treatments have both
      in vitro and in vivo data showing them to be efficacious if the surface integrity
      of the lesion is not breached. Once this has occurred, the rationale for cutting
      off the nutrient supplies to the pathogenic bacteria without the removal of the
      infected dentine, a noninvasive restorative technique, is discussed using
      existing clinical studies as examples. Finally two novel noninvasive restorative
      techniques using fluorohydroxyapatite crystals are described. The need for
      clinical data in support of emerging caries-preventive and restorative strategies
      is emphasized.

PMID- 25871415
TI  - The future of fluorides and other protective agents in erosion prevention.
AB  - The effectiveness of fluoride in caries prevention has been convincingly proven.
      In recent years, researchers have investigated the preventive effects of
      different fluoride formulations on erosive tooth wear with positive results, but
      their action on caries and erosion prevention must be based on different
      requirements, because there is no sheltered area in the erosive process as there
      is in the subsurface carious lesions. Thus, any protective mechanism from
      fluoride concerning erosion is limited to the surface or the near surface layer
      of enamel. However, reports on other protective agents show superior preventive
      results. The mechanism of action of tin-containing products is related to tin
      deposition onto the tooth surface, as well as the incorporation of tin into the
      near-surface layer of enamel. These tin-rich deposits are less susceptible to
      dissolution and may result in enhanced protection of the underlying tooth.
      Titanium tetrafluoride forms a protective layer on the tooth surface. It is
      believed that this layer is made up of hydrated hydrogen titanium phosphate.
      Products containing phosphates and/or proteins may adsorb either to the pellicle,
      rendering it more protective against demineralization, or directly to the dental
      hard tissue, probably competing with H(+) at specific sites on the tooth surface.
      Other substances may further enhance precipitation of calcium phosphates on the
      enamel surface, protecting it from additional acid impacts. Hence, the future of
      fluoride alone in erosion prevention looks grim, but the combination of fluoride
      with protective agents, such as polyvalent metal ions and some polymers, has much
      brighter prospects.

PMID- 25871416
TI  - Role of host-derived proteinases in dentine caries and erosion.
AB  - Demineralization in dentinal caries and erosion exposes dentine organic matrix.
      This exposed matrix, containing type I collagen and non-collagenous proteins, is
      then degraded by host collagenolytic enzymes, matrix metalloproteinases (MMPs)
      and cysteine cathepsins. The knowledge of the identities and function of these
      enzymes in dentine has accumulated only within the last 15 years, but has already
      formed a field of research called 'dentine degradomics'. This research has
      demonstrated the role of endogenous collagenolytic enzymes in caries and erosion
      development. In demineralized dentine, the enzymes degrade triple-helical
      collagen molecules, leading to the gradual loss of collagen matrix. Even before
      that, they can cleave off the terminal non-helical ends of collagen molecules
      called telopeptides, leading to the structural changes at the intramolecular gap
      areas, which may affect or even prevent intrafibrillar remineralization, which is
      considered essential in restoring the dentine's mechanical properties. They may
      also cause the loss of non-collagenous proteins that could serve as nucleation
      sites for remineralization. Here we review the findings demonstrating that
      inhibition of salivary or dentine endogenous MMPs and cysteine cathepsins may
      provide preventive means against the progression of caries or erosion.
      Furthermore, we also suggest the future directions for the new experimental
      preventive research to gain more knowledge of the enzymes and their function
      during and after dentine demineralization, and the pathways to find the
      clinically acceptable means to prevent the functional activity of these enzymes.

PMID- 25871417
TI  - Natural products and caries prevention.
AB  - Dental caries is considered as the most common polymicrobial oral disease in the
      world. With the aim of developing alternative approaches to reduce or prevent the
      decay, numerous papers showed the potential anticaries activity of a number of
      natural products. The natural products with anticaries effects are selected from
      e.g. food, beverages, flowers or traditional herbs. Most of the effective
      components are proven to be polyphenol compounds. Many of the natural products
      are studied as antibacterial agents, while some of them are found to be effective
      in shifting the de-/remineralization balance. However, the mechanisms of the
      anticaries effects are still unclear for most of the natural products. In the
      future, more efforts need to be made to seek novel effective natural products via
      in vitro experiment, animal study and in situ investigations, as well as to
      enhance their anticaries effects with the help of novel technology like
      nanotechnology.

PMID- 25871418
TI  - Ecological approaches to oral biofilms: control without killing.
AB  - Humans have co-evolved with micro-organisms and have a symbiotic or mutualistic
      relationship with their resident microbiome. As at other body surfaces, the mouth
      has a diverse microbiota that grows on oral surfaces as structurally and
      functionally organised biofilms. The oral microbiota is natural and provides
      important benefits to the host, including immunological priming, down-regulation
      of excessive pro-inflammatory responses, regulation of gastrointestinal and
      cardiovascular systems, and colonisation by exogenous microbes. On occasions,
      this symbiotic relationship breaks down, and previously minor components of the
      microbiota outcompete beneficial bacteria, thereby increasing the risk of
      disease. Antimicrobial agents have been formulated into many oral care products
      to augment mechanical plaque control. A delicate balance is needed, however, to
      control the oral microbiota at levels compatible with health, without killing
      beneficial bacteria and losing the key benefits delivered by these resident
      microbes. These antimicrobial agents may achieve this by virtue of their
      recommended twice daily topical use, which results in pharmacokinetic profiles
      indicating that they are retained in the mouth for relatively long periods at
      sublethal levels. At these concentrations they are still able to inhibit
      bacterial traits implicated in disease (e.g. sugar transport/acid production;
      protease activity) and retard growth without eliminating beneficial species. In
      silico modelling studies have been performed which support the concept that
      either reducing the frequency of acid challenge and/or the terminal pH, or by
      merely slowing bacterial growth, results in maintaining a community of beneficial
      bacteria under conditions that might otherwise lead to disease (control without
      killing).

PMID- 25871419
TI  - Towards understanding oral health.
AB  - During the last century, dental research has focused on unraveling the mechanisms
      behind various oral pathologies, while oral health was typically described as the
      mere absence of oral diseases. The term 'oral microbial homeostasis' is used to
      describe the capacity of the oral ecosystem to maintain microbial community
      stability in health. However, the oral ecosystem itself is not stable: throughout
      life an individual undergoes multiple physiological changes while progressing
      through infancy, childhood, adolescence, adulthood and old age. Recent
      discussions on the definition of general health have led to the proposal that
      health is the ability of the individual to adapt to physiological changes, a
      condition known as allostasis. In this paper the allostasis principle is applied
      to the oral ecosystem. The multidimensionality of the host factors contributing
      to allostasis in the oral cavity is illustrated with an example on changes
      occurring in puberty. The complex phenomenon of oral health and the processes
      that prevent the ecosystem from collapsing during allostatic changes in the
      entire body are far from being understood. As yet individual components (e.g.
      hard tissues, microbiome, saliva, host response) have been investigated, while
      only by consolidating these and assessing their multidimensional interactions
      should we be able to obtain a comprehensive understanding of the ecosystem, which
      in turn could serve to develop rational schemes to maintain health. Adapting such
      a 'system approach' comes with major practical challenges for the entire research
      field and will require vast resources and large-scale multidisciplinary
      collaborations.

PMID- 25871420
TI  - The course and impact of family optimism in the post-acute period after acquired
      brain injury.
AB  - OBJECTIVE: To investigate the course and impact of family optimism in the post
      acute stage of acquired brain injury. METHODS: At Time 1, 30 family relatives of
      in-patients in rehabilitation units and 30 relatives of patients recently
      discharged from such units completed questionnaires relating to their emotional
      health, engagement in the rehabilitation process and expectations about the
      future consequences and controllability of the injury. At Time 2 (12-18 months
      later), 23 of the original sample completed questionnaires about their emotional
      health and actual consequences and controllability of the injury. RESULTS: At
      Time 1, optimism about future consequences and controllability was associated
      with greater engagement in the rehabilitation process and better emotional
      health. The two groups did not differ on any of the measures, which did not
      support the expectation that the patient's discharge home would trigger a loss of
      optimism and emotional upset for the family. At Time 2, the actual consequences
      were worse than had been expected at Time 1 and greater disappointment was
      associated with a greater decline in emotional wellbeing. CONCLUSION: Family
      expectations about recovery are linked with important variables such as emotional
      wellbeing and engagement in the rehabilitation process and need careful
      management by clinicians.

PMID- 25871421
TI  - Understanding the role of probiotics in coeliac disease.

PMID- 25871423
TI  - Respiratory effects of adaptive servoventilation therapy in patients with heart
      failure and Cheyne-Stokes respiration compared to healthy volunteers.
AB  - BACKGROUND: Nocturnal adaptive servoventilation (ASV) therapy is now frequently
      used to treat Cheyne-Stokes respiration (CSR), which is highly prevalent in
      patients with moderate-to-severe heart failure (HF) and characterized by
      periodical breathing (hyperventilation). OBJECTIVES: This study analyzed and
      compared the acute effects of a novel ASV device on carbon dioxide pressure
      (pCO2) and oxygen saturation (SaO2) in HF patients with CSR and healthy
      volunteers. The influence of being asleep or awake on the ASV algorithm was also
      determined. METHODS: All subjects underwent ASV (PaceWaveTM, ResMed) for 1 h.
      Transcutaneous pCO2 (PtcCO2) and SaO2 were assessed transcutaneously, while
      wakefulness was analyzed using EEG recordings. Assessments were made 30 min
      before and after ASV, and during 1 h of ASV. RESULTS: Twenty HF patients (19
      male; age 79 +/- 12 years) and 15 volunteers (13 male, age 25 +/- 4 years) were
      included. When awake, ASV was associated with a trend towards a decrease in
      PtcCO2 and an increase in SaO2 versus baseline in HF patients (34.4 +/- 3.2 to
      33.7 +/- 3.8 mm Hg and 93.8 +/- 2.6 to 94.9 +/- 2.6%, respectively) and
      volunteers (39.5 +/- 3.0 to 38.2 +/- 3.8 mm Hg and 96.9 +/- 1.3 to 97.8 +/-
      0.9%). While asleep during ASV, PtcCO2 increased to 36.3 +/- 3.8 mm Hg and SaO2
      decreased to 93.8 +/- 2.6% in HF patients, with similar changes in volunteers
      (PtcCO2 41.7 +/- 3.0 mm Hg, SaO2 97.1 +/- 1.2). All comparisons were
      statistically significant (p <= 0.05, except the PtcCO2 decrease in both groups
      when awake). CONCLUSIONS: ASV therapy might result in hyperventilation when
      subjects are awake, but while asleep, PtcCO2 increased to mid-normal values,
      effects that would be favorable in HF patients with CSR.

PMID- 25871422
TI  - Leptin in the canine uterus and placenta: possible implications in pregnancy.
AB  - BACKGROUND: Leptin (Lep) is known for its involvement in the regulation of
      reproductive functions. It is important for uterine receptivity, implantation,
      placental growth and maternal energy homeostasis in several species, but Lep's
      function in the pregnant dog has not been investigated. METHODS: Pregnant bitches
      were ovariohysterectomized at pre-implantation, post-implantation, mid-gestation
      and prepartum luteolysis. Two additional groups were treated with aglepristone in
      mid-gestation, and ovariohysterectomized 24 or 72 h later. Lep and leptin
      receptor (LepR) gene expression was detected by semi-quantitative real-time PCR
      in pre-implantation and inter-placental uterine sections (Ut) and in utero
      placental compartments (Ut/Pl). Immunohistochemistry and in situ hybridization
      (ISH) were performed for Lep and LepR protein and mRNA localization. Parametric
      one-way ANOVA, paired t-test and Wilcoxon signed-rank test were used for
      statistical analysis. RESULTS: In the Ut/Pl, Lep expression was higher at post
      implantation and prepartum luteolysis than at mid-gestation, while in the Ut, Lep
      mRNA levels did not change during pregnancy. LepR expression in the Ut/Pl was up
      regulated at prepartum luteolysis compared to the earlier stages. In the Ut,
      highest LepR mRNA was found at pre- and post-implantation. LepR expression was
      down-regulated in the Ut/Pl compared to the Ut at post-implantation and at mid
      gestation. Aglepristone treatment resulted in a decrease of Lep mRNA levels from
      24 to 72 h in the Ut without concomitant changes in the Ut/Pl or in LepR levels.
      Lep and LepR immunoreactivities were strong in the luminal and glandular
      epithelium in the Ut with abundant LepR signals in the subepithelial stroma. In
      the Ut/Pl, fetal trophoblasts stained stronger for Lep and LepR than decidual
      cells, and signals for both proteins were also detected in the glandular
      chambers. The myometrium, blood vessel media, and sporadically also the
      endothelium stained for Lep and LepR. ISH showed similar signal distribution in
      the Ut and Ut/Pl. CONCLUSIONS: Lep and LepR are differentially expressed in the
      canine uterus and placenta during pregnancy, and their presence in various cell
      types indicates paracrine/autocrine roles. The Lep signaling system may be one of
      the pathways involved in feto-maternal cross-talk, implantation and maintenance
      of pregnancy, and may have a regulatory role around parturition.

PMID- 25871424
TI  - Stress Response to the Functional Magnetic Resonance Imaging Environment in
      Healthy Adults Relates to the Degree of Limbic Reactivity during Emotion
      Processing.
AB  - BACKGROUND: Imaging techniques are increasingly being used to examine the neural
      correlates of stress and emotion processing; however, relations between the
      primary stress hormone cortisol, the functional magnetic resonance imaging (fMRI)
      environment, and individual differences in response to emotional challenges are
      not yet well studied. The present study investigated whether cortisol activity
      prior to, and during, an fMRI scan may be related to neural processing of
      emotional information. METHODS: Twenty-six healthy individuals (10 female)
      completed a facial emotion perception test during 3-tesla fMRI. RESULTS: Prescan
      cortisol was significantly correlated with enhanced amygdala, hippocampal, and
      subgenual cingulate reactivity for facial recognition. Cortisol change from pre-
      to postscanning predicted a greater activation in the precuneus for both fearful
      and angry faces. A negative relationship between overall face accuracy and
      activation in limbic regions was observed. CONCLUSION: Individual differences in
      response to the fMRI environment might lead to a greater heterogeneity of brain
      activation in control samples, decreasing the power to detect differences between
      clinical and comparison groups. (c) 2015 S. Karger AG, Basel.

PMID- 25871425
TI  - Occupational rights and critical occupational therapy: rising to the challenge.

PMID- 25871426
TI  - G4-quartet.M(+) borate hydrogels.
AB  - The ability to modulate the physical properties of a supramolecular hydrogel may
      be beneficial for biomaterial and biomedical applications. We find that guanosine
      (G 1), when combined with 0.5 equiv of potassium borate, forms a strong, self
      supporting hydrogel with elastic moduli >10 kPa. The countercation in the borate
      salt (MB(OH)4) significantly alters the physical properties of the hydrogel. The
      gelator combination of G 1 and KB(OH)4 formed the strongest hydrogel, while the
      weakest system was obtained with LiB(OH)4, as judged by (1)H NMR and rheology.
      Data from powder XRD, (1)H double-quantum solid-state magic-angle spinning (MAS)
      NMR and small-angle neutron scattering (SANS) were consistent with a structural
      model that involves formation of borate dimers and G4.K(+) quartets by G 1 and
      KB(OH)4. Stacking of these G4.M(+) quartets into G4-nanowires gives a hydrogel.
      We found that the M(+) cation helps stabilize the anionic guanosine-borate (GB)
      diesters, as well as the G4-quartets. Supplementing the standard gelator mixture
      of G 1 and 0.5 equiv of KB(OH)4 with additional KCl or KNO3 increased the
      strength of the hydrogel. We found that thioflavin T fluoresces in the presence
      of G4.M(+) precursor structures. This fluorescence response for thioflavin T was
      the greatest for the K(+) GB system, presumably due to the enhanced interaction
      of the dye with the more stable G4.K(+) quartets. The fluorescence of thioflavin
      T increased as a function of gelator concentration with an increase that
      correlated with the system's gel point, as measured by solution viscosity. 

PMID- 25871428
TI  - Genistein inhibits human colorectal cancer growth and suppresses miR-95, Akt and
      SGK1.
AB  - BACKGROUND: Genistein, a major isoflavonoid isolated from dietary soybean, has
      been shown to suppress the growth of several cancers through modulation of
      various pathways. However, the molecular mechanisms by which genistein elicit its
      effects on colorectal cancer (CRC) cells have not been fully elucidated. In this
      study, we aimed to investigate the anti-tumor activities of genistein on CRC and
      its potential mechanism. METHODS: Effects of genistein on the cell proliferation
      were tested in HCT-116 cells by MTT assay, and apoptosis was measured by Flow
      cytometry. Real-time PCR was also used to evaluate the regulation of genistein on
      miR-95, Akt and SGK1 expression. The protein levels of total Akt (T-Akt), and
      phosphorylated Akt (P-Akt) were assessed by western blot. A nude mice xenograft
      model was employed to determine whether genistein could have an anti-tumor effect
      on CRC in vivo. RESULTS: We found that treatment of HCT-116 cells with genistein
      caused an inhibition of cell proliferation and induction of apoptosis. Meanwhile,
      genistein down-regulated the mRNA expression of Akt, SGK1 and miR-95, and
      inhibited the phosphorylation of Akt in HCT-116 cells. The experiment in vivo
      also showed that genistein significantly suppressed the growth of mouse xenograft
      tumor. CONCLUSION: This study demonstrates that genistein has an inhibitory
      effect on CRC involved in reducing miR-95, Akt and SGK1, offering novel insights
      into the mechanisms of genistein therapeutic actions.

PMID- 25871429
TI  - Imaging Structure and Composition Homogeneity of 300 mm SiGe Virtual Substrates
      for Advanced CMOS Applications by Scanning X-ray Diffraction Microscopy.
AB  - Advanced semiconductor heterostructures are at the very heart of many modern
      technologies, including aggressively scaled complementary metal oxide
      semiconductor transistors for high performance computing and laser diodes for low
      power solid state lighting applications. The control of structural and
      compositional homogeneity of these semiconductor heterostructures is the key to
      success to further develop these state-of-the-art technologies. In this article,
      we report on the lateral distribution of tilt, composition, and strain across
      step-graded SiGe strain relaxed buffer layers on 300 mm Si(001) wafers treated
      with and without chemical-mechanical polishing. By using the advanced synchrotron
      based scanning X-ray diffraction microscopy technique K-Map together with micro
      Raman spectroscopy and Atomic Force Microscopy, we are able to establish a
      partial correlation between real space morphology and structural properties of
      the sample resolved at the micrometer scale. In particular, we demonstrate that
      the lattice plane bending of the commonly observed cross-hatch pattern is caused
      by dislocations. Our results show a strong local correlation between the strain
      field and composition distribution, indicating that the adatom surface diffusion
      during growth is driven by strain field fluctuations induced by the underlying
      dislocation network. Finally, it is revealed that a superficial chemical
      mechanical polishing of cross-hatched surfaces does not lead to any significant
      change of tilt, composition, and strain variation compared to that of as-grown
      samples. 

PMID- 25871427
TI  - Social cognitive training in adolescents with chromosome 22q11.2 deletion
      syndrome: feasibility and preliminary effects of the intervention.
AB  - BACKGROUND: Children with chromosome 22q11.2 deletion syndrome (22q11DS) often
      have deficits in social cognition and social skills that contribute to poor
      adaptive functioning. These deficits may be of relevance to the later occurrence
      of serious psychiatric illnesses such as schizophrenia. Yet, there are no
      evidence-based interventions to improve social cognitive functioning in children
      with 22q11DS. METHODS: Using a customised social cognitive curriculum, we
      conducted a pilot small-group-based social cognitive training (SCT) programme in
      13 adolescents with 22q11DS, relative to a control group of nine age- and gender
      matched adolescents with 22q11DS. RESULTS: We found the SCT programme to be
      feasible, with high rates of compliance and satisfaction on the part of the
      participants and their families. Our preliminary analyses indicated that the
      intervention group showed significant improvements in an overall social cognitive
      composite index. CONCLUSIONS: SCT in a small-group format for adolescents with
      22q11DS is feasible and results in gains in social cognition. A larger randomised
      controlled trial would permit assessment of efficacy of this promising novel
      intervention.

PMID- 25871430
TI  - Isolation of >1 nm Diameter Single-Wall Carbon Nanotube Species Using Aqueous Two
      Phase Extraction.
AB  - In this contribution we demonstrate the effective separation of single-wall
      carbon nanotube (SWCNT) species with diameters larger than 1 nm through
      multistage aqueous two-phase extraction (ATPE), including isolation at the near
      monochiral species level up to at least the diameter range of SWCNTs synthesized
      by electric arc synthesis (1.3-1.6 nm). We also demonstrate that refined species
      are readily obtained from both the metallic and semiconducting subpopulations of
      SWCNTs and that this methodology is effective for multiple SWCNT raw materials.
      Using these data, we report an empirical function for the necessary surfactant
      concentrations in the ATPE method for separating different SWCNTs into either the
      lower or upper phase as a function of SWCNT diameter. This empirical correlation
      enables predictive separation design and identifies a subset of SWCNTs that
      behave unusually as compared to other species. These results not only
      dramatically increase the range of SWCNT diameters to which species selective
      separation can be achieved but also demonstrate that aqueous two-phase
      separations can be designed across experimentally accessible ranges of surfactant
      concentrations to controllably separate SWCNT populations of very small (~0.62
      nm) to very large diameters (>1.7 nm). Together, the results reported here
      indicate that total separation of all SWCNT species is likely feasible by the
      ATPE method, especially given future development of multistage automated
      extraction techniques. 

PMID- 25871431
TI  - Cardiac-specific PID1 overexpression enhances pressure overload-induced cardiac
      hypertrophy in mice.
AB  - BACKGROUND/AIMS: PID1 was originally described as an insulin sensitivity
      relevance protein, which is also highly expressed in heart tissue. However, its
      function in the heart is still to be elucidated. Thus this study aimed to
      investigate the role of PID1 in the heart in response to hypertrophic stimuli.
      METHODS: Samples of human failing hearts from the left ventricles of dilated
      cardiomyopathy (DCM) patients undergoing heart transplants were collected.
      Transgenic mice with cardiomyocyte-specific overexpression of PID1 were
      generated, and cardiac hypertrophy was induced by transverse aortic constriction
      (TAC). The extent of cardiac hypertrophy was evaluated by echocardiography as
      well as pathological and molecular analyses of heart samples. RESULTS: A
      significant increase in PID1 expression was observed in failing human hearts and
      TAC-treated wild-type mouse hearts. When compared with TAC-treated wild-type
      mouse hearts, PID1-TG mouse showed a significant exacerbation of cardiac
      hypertrophy, fibrosis, and dysfunction. Further analysis of the signaling pathway
      in vivo suggested that these adverse effects of PID1 were associated with the
      inhibition of AKT, and activation of MAPK pathway. CONCLUSION: Under pathological
      conditions, over-expression of PID1 promotes cardiac hypertrophy by regulating
      the Akt and MAPK pathway.

PMID- 25871432
TI  - Utility of Tc-PEG4-E[PEG4-c(RGDfK)]2 in Posttherapy Surveillance of Patients with
      Reelevated Carcinoembryonic Antigen Levels.
AB  - OBJECTIVES: To evaluate the efficacy of (99m)Tc-PEG4-E[PEG4-c (RGDfK)]2 ((99m)Tc
      3PRGD2) single photon emission computed tomography (SPECT) in monitoring the
      recurrence of malignancies. MATERIALS AND METHODS: (99m)Tc-3PRGD2 SPECT was
      performed on 28 patients (10 females and 18 males; median age 49.2 years)
      suspected of recurrent malignancies due to an asymptomatically reelevated
      carcinoembryonic antigen level. The SPECT was performed 0.5 h after an
      intravenous injection of 11.1 MBq/kg (0.3 mCi/kg) of (99m)Tc-3PRGD2. The SPECT
      and concurrent contrast-enhanced computed tomography (ceCT) findings were
      analyzed with reference to the histopathological findings and/or clinical follow
      up data. RESULTS: Recurrences were identified in 20 out of the 28 patients
      (prevalence 71.4%) with altogether 26 lesions. Fifteen lesions were confirmed by
      histopathological findings, and the other 11 lesions were confirmed by serial
      radiological or clinical follow-up. Of the 20 patients with recurrent
      malignancies, 12 (60%) were correctly identified by (99m)Tc-3PRGD2 SPECT. In the
      patient-based analysis, the sensitivity and specificity of (99m)Tc-3PRGD2 SPECT
      were 60 and 100%, respectively, and the positive and negative predictive values
      were 100 and 50%, respectively. In the lesion-based evaluation, the sensitivity
      and specificity were 62 and 100%, respectively. The sensitivity and specificity
      of the ceCT in the patient-based evaluation were 60 and 75%, respectively, and
      the positive and negative predictive values were 86 and 40%, respectively. In the
      lesion-based evaluation, the sensitivity and specificity of the ceCT were 70 and
      84%, respectively. CONCLUSIONS: (99m)Tc-3PRGD2, as a new SPECT tracer targeting
      the integrin alphavbeta3 receptor, was more useful in distinguishing recurrences
      as compared to ceCT.

PMID- 25871433
TI  - Posterior reversible encephalopathy syndrome in end-stage kidney disease: not
      strictly posterior or reversible.
AB  - Posterior reversible encephalopathy syndrome (PRES) is an uncommon clinico
      radiological condition that can result in severe brain injury. The pathogenesis
      of cerebral vasogenic edema, the hallmark of PRES, is not fully understood.
      Despite its name, there is substantial heterogeneity both in terms of imaging
      findings and outcome. Relatively little is known about PRES in kidney disease
      despite the clustering of risk factors including hypertension, autoimmune disease
      and immunosuppression. In a retrospective observational study of incident end
      stage kidney disease patients in Southwest Ireland over a ten year period, we
      discovered five cases of PRES representing an incidence of 0.84% in this patient
      population. These five cases highlight the variability in clinical presentation
      and the potentially life-threatening nature of this condition. We provide an in
      depth review of the existing literature regarding PRES in terms of its
      pathogenesis and heterogeneity, as well as the experience of PRES in ESKD
      patients. PRES appears to be rare in the ESKD population but could be under
      recognized. Marked hypertension is a cardinal risk factor in this population,
      associated with extracellular fluid volume expansion. Neuroimaging findings can
      be diverse involving both anterior and posterior circulation territories. Three
      of the five patients described had commenced haemodialysis within four weeks of
      their presentation. These patients may be particularly vulnerable to
      microvascular brain injury, which can be devastating. This emphasises the need
      for clinicians to pay meticulous attention to extracellular fluid volume control
      during this potentially hazardous period.

PMID- 25871434
TI  - The State of the Art in Biosynthesis of Anthocyanins and Its Regulation in
      Pigmented Sweet Oranges [(Citrus sinensis) L. Osbeck].
AB  - Anthocyanins are water-soluble pigments belonging to the flavonoid compound
      family involved in nature in several aspects of plant development and defense. By
      bestowing much of the color and flavor on fruits and vegetables, they are
      components of the human diet and, thanks to their radical-scavenging properties,
      are not considered exclusively as food products but also as therapeutic agents.
      Several cultivars of red (or blood) oranges [Citrus sinensis (L.) Osbeck], such
      as Tarocco, Moro, and Sanguinello, are characterized by the presence of
      anthocyanins in both the rind and fruit juice vesicles. The amount and
      composition of anthocyanins in the pigmented orange cultivar vary greatly
      depending on variety, maturity, region of cultivation, and many other
      environmental conditions. Most of the blood orange varieties require a wide day
      night thermal range to maximize color formation. Therefore, the production of red
      oranges characterized by high anthocyanin levels is limited to a few regions and
      in particular to the Sicilian area around Mount Etna in Italy, where the
      characteristic climate conditions yield fruits of unique color intensity and
      quality. In this review, both the basic information and the most recent advances
      in red orange anthocyanins are reported, with intense attention given to their
      biosynthesis and regulation. 

PMID- 25871436
TI  - Cloning and expression of a novel target fusion protein and its application in
      anti-tumor therapy.
AB  - BACKGROUNDS: Epidermal growth factor (EGF) is a 53 amino acid polypeptide and its
      receptor EGFR is an established therapeutic target for anti-tumor therapy. Two
      major categories of EGFR-targeted drugs include monoclonal antibodies (mAbs) and
      small molecular tyrosine kinase inhibitors (TKIs). However, drug resistance
      occurs in a significant proportion of patients due to EGFR mutations. Since EGFR
      can maintain activation while abrogating the activity of mAbs or TKIs, or bypass
      signaling functions while successfully circumventing the EGF-EGFR switch,
      developing new mechanism-based inhibitors is necessary. METHODS: In this study,
      based on the principle of tumor immunotherapy, a recombinant protein pLLO-hEGF
      was constructed. The N-terminal portion contains three immunodominant epitopes
      from listeriolysin O (LLO) and the C-terminal includes EGF. To use EGF as a
      target vector to recognize EGFR-expressing cancer cells, immunodominant epitopes
      could enhance immunogenicity of tumor cells for immune cell activation and
      attack. RESULTS: Recombinant protein pLLO-hEGF was successfully expressed and
      showed strong affinity to cancer cells. Also, pLLO-hEGF could significantly
      stimulate human lymphocyte proliferation and the lymphocytes demonstrated
      enhanced killing potency in EGFR-expressing cancer cells in vitro and in vivo.
      CONCLUSION: This study can provide novel strategies and directions in tumor
      biotherapy.

PMID- 25871437
TI  - Bioelectric impedance analysis of body composition of children and adolescents
      with sickle cell anemia in Enugu, Nigeria.
AB  - BACKGROUND: Body composition indices are widely used to evaluate growth and
      nutrition in children, particularly those with sickle cell anemia (SCA), who are
      known to have impaired growth, impaired skeletal maturation, and delayed puberty.
      The current study is aimed at determining the body composition of children with
      SCA. METHODS: Consecutive selection of SCA children aged 6 to 18 years, who
      served as subjects and their age and gender matched children with HbAA
      (controls), selected using multi-stage systematic sampling. It was a cross
      sectional descriptive study conducted at the pediatric hematology and oncology
      clinic. Bioelectric impedance analysis was used to determine the body composition
      parameters, including weight, body fat percentage (BFP), visceral fat percentage,
      body mass index (BMI), skeletal muscle percentage, and resting metabolic rate.
      Data were analyzed using SPSS 16.0 at P < 0.05. RESULTS: One hundred and thirty
      two subjects and controls respectively were studied. Subjects had lower body
      composition parameters compared with controls, with the older male subjects aged
      10 to 18 years, having lower body composition indices (weight, height, BMI, and
      BFP) compared with controls. Visceral fat percentage was low in both subjects and
      controls. CONCLUSIONS: Children with SCA, particularly the older males, have
      impaired body composition indices. There is a need to conduct further studies to
      determine the longitudinal aspects of growth as well as quantitative and
      qualitative assessment of nutritional intake in children with SCA, which will
      inform higher alimentation requirements for HbSS children as compared with HbAA
      individuals.

PMID- 25871438
TI  - Rheological influence upon the glomerular podocyte and resultant
      mechanotransduction.
AB  - The glomerular podocyte is exposed to numerous mechanical forces as a constituent
      of the glomerular filtration apparatus. This includes fluid shear stress (FSS)
      displaced upon the podocytic foot process's apical, lateral, and basal surfaces.
      Even in the face of continuous flow the podocyte is capable of contributing to
      physiologic filtration, however with pathologic levels of hyperfiltration there
      is increased FSS placed upon the cell. The mechanisms by which the podocyte
      detects and responds to FSS are topics of recent investigations, with the aim to
      clarify the way these cells are injured and/or adapt in times of hyperfiltration
      and disease states. As the pathogenesis of numerous glomerulopathies is
      contingent on the status of the podocyte, understanding the manner that these
      cells can be modified by FSS is essential. Likewise, determination of the effect
      of such mechanical forces upon other resident cells of the renal corpuscle would
      reveal the contribution of FSS in the progression of glomerular diseases. The
      biochemical manner in which podocytes sense and respond to FSS, that is
      mechanotransduction, will be discussed.

PMID- 25871439
TI  - Quantification of in vivo 31P NMR brain spectra using LCModel.
AB  - Quantification of (31)P NMR spectra is commonly performed using line-fitting
      techniques with prior knowledge. Currently available time- and frequency-domain
      analysis software includes AMARES (in jMRUI) and CFIT respectively. Another
      popular frequency-domain approach is LCModel, which has been successfully used to
      fit both (1)H and (13)C in vivo NMR spectra. To the best of our knowledge LCModel
      has not been used to fit (31)P spectra. This study demonstrates the feasibility
      of using LCModel to quantify in vivo (31)P MR spectra, provided that adequate
      prior knowledge and LCModel control parameters are used. Both single-voxel and
      MRSI data are presented, and similar results are obtained with LCModel and with
      AMARES. This provides a new method for automated, operator-independent analysis
      of (31)P NMR spectra.

PMID- 25871440
TI  - Antiplasmodial and Cytotoxic Triterpenoids from the Bark of the Cameroonian
      Medicinal Plant Entandrophragma congoense.
AB  - Eight new triterpenoids, prototiamins A-G (1-6, 9) and seco-tiaminic acid A (10),
      were isolated along with four known compounds from the bark of Entandrophragma
      congoense. Their structures were elucidated by means of HRMS and different NMR
      techniques and chemical transformations. Assignments of relative and absolute
      configurations for the new compounds were achieved using NOESY experiments and by
      chemical modification including the advanced Mosher's method. Additionally, the
      structure and relative configuration of compound 3 were confirmed by single
      crystal X-ray diffraction analysis. Compounds 1, 3, and 5 displayed significant
      in vitro antiplasmodial activity against the erythrocytic stages of chloroquine
      sensitive Plasmodium falciparum strain NF54. Prototiamin C (3) was the most
      potent of the compounds isolated, with an IC50 value of 0.44 MUM. All compounds
      tested showed low cytotoxicity for the L6 rat skeletal myoblast cell line. 

PMID- 25871442
TI  - Monitoring matrix metalloproteinase activity at the epidermal-dermal interface by
      SILAC-iTRAQ-TAILS.
AB  - Secreted proteases act on interstitial tissue secretomes released from multiple
      cell types. Thus, substrate proteins might be part of higher molecular complexes
      constituted by many proteins with diverse and potentially unknown cellular
      origin. In cell culture, these may be reconstituted by mixing native secretomes
      from different cell types prior to incubation with a test protease. Although
      current degradomics techniques could identify novel substrate proteins in these
      complexes, all information on the cellular origin is lost. To address this
      limitation, we combined iTRAQ-based terminal amine isotopic labeling of
      substrates (iTRAQ-TAILS) with SILAC to assign proteins to a specific cell type by
      MS1- and their cleavage by MS2-based quantification in the same experiment. We
      demonstrate the power of our newly established workflow by monitoring matrix
      metalloproteinase (MMP) 10 dependent cleavages in mixtures from light-labeled
      keratinocyte and heavy-labeled fibroblast secretomes. This analysis correctly
      assigned extracellular matrix components, such as laminins and collagens, to
      their respective cellular origins and revealed their processing in an MMP10
      dependent manner. Hence, our newly devised degradomics workflow facilitates
      deeper insight into protease activity in complex intercellular compartments such
      as the epidermal-dermal interface by integrating multiple modes of quantification
      with positional proteomics. All MS data have been deposited in the
      ProteomeXchange with identifier PXD001643
      (http://proteomecentral.proteomexchange.org/dataset/PXD001643). 

PMID- 25871441
TI  - Evaluation of CADD Scores in Curated Mismatch Repair Gene Variants Yields a Model
      for Clinical Validation and Prioritization.
AB  - Next-generation sequencing in clinical diagnostics is providing valuable genomic
      variant data, which can be used to support healthcare decisions. In silico tools
      to predict pathogenicity are crucial to assess such variants and we have
      evaluated a new tool, Combined Annotation Dependent Depletion (CADD), and its
      classification of gene variants in Lynch syndrome by using a set of 2,210 DNA
      mismatch repair gene variants. These had already been classified by experts from
      InSiGHT's Variant Interpretation Committee. Overall, we found CADD scores do
      predict pathogenicity (Spearman's rho = 0.595, P < 0.001). However, we discovered
      31 major discrepancies between the InSiGHT classification and the CADD scores;
      these were explained in favor of the expert classification using population
      allele frequencies, cosegregation analyses, disease association studies, or a
      second-tier test. Of 751 variants that could not be clinically classified by
      InSiGHT, CADD indicated that 47 variants were worth further study to confirm
      their putative pathogenicity. We demonstrate CADD is valuable in prioritizing
      variants in clinically relevant genes for further assessment by expert
      classification teams. 

PMID- 25871444
TI  - Graphene Aerogels Decorated with alpha-FeOOH Nanoparticles for Efficient
      Adsorption of Arsenic from Contaminated Waters.
AB  - Arsenic (As) is the world's most hazardous chemical found in drinking water of
      many countries; therefore, there is an urgent need for the development of low
      cost adsorbents for its removal. Here, we report a highly versatile and synthetic
      route for the preparation of a three-dimensional (3D) graphene-iron oxide
      nanoparticle aerogel composite for the efficient removal of As from contaminated
      water. This unique three-dimensional (3D) interconnected network was prepared
      from natural graphite rocks with a simple reaction, without the use of harsh
      chemicals, which combines with the exfoliation of graphene oxide (GO) sheets via
      the reduction of ferrous ion to form a graphene aerogel composite decorated with
      iron oxide nanoparticles. The prepared adsorbent showed outstanding absorption
      performance for the removal of As from contaminated water, because of its high
      surface-to-volume ratio and characteristic pore network in the 3D architecture.
      The performed case study using real drinking water contaminated with As under
      batch conditions showed successful removal of arsenic to the concentration
      recommended by the World Health Organisation (WHO). 

PMID- 25871443
TI  - High Prevalence of Obstructive Sleep Apnea in Patients with Moderate to Severe
      Chronic Obstructive Pulmonary Disease.
AB  - RATIONALE: When obstructive sleep apnea (OSA) and chronic obstructive pulmonary
      disease (COPD) coexist in the so-called "overlap" syndrome, a high risk for
      mortality and morbidity has been reported. There is controversy about the
      prevalence of OSA in people affected by COPD. OBJECTIVES: The purpose of this
      study was to investigate objective meaures of sleep-disordered breathing in
      patients with moderate to severe COPD to test the hypothesis that COPD is
      associated with an increased prevalence of OSA. METHODS: Fifty-four patients (54%
      men) with moderate to severe COPD were enrolled prospectively (mean +/- SD, FEV1
      = 42.8 +/- 19.8% predicted, and FEV1/FVC = 42.3 +/- 13.1). Twenty patients (37%)
      were on supplemental oxygen at baseline. Exercise tolerance; questionnaires
      related to symptoms, sleep, and quality of life; and home polysomnography were
      obtained. MEASUREMENTS AND MAIN RESULTS: Forty-four patients had full
      polysomnography suitable for analysis. OSA (apnea-hypopnea index > 5/h) was
      present in 29 subjects (65.9%). Sleep efficiency was poor in 45% of subjects.
      CONCLUSIONS: OSA is highly prevalent in patients with moderate to severe COPD
      referred to pulmonary rehabilitation. Sleep quality is also poor among this
      selected group. These patients have greater-than-expected sleep-disordered
      breathing, which could be an important contributory factor to morbidity and
      mortality. Pulmonary rehabilitation programs should consider including a sleep
      assessment in patients with moderate to severe COPD and interventions when
      indicated to help reduce the impact of OSA in COPD.

PMID- 25871445
TI  - Overactive bladder in adults with sickle cell disease.
AB  - AIMS: To characterize the prevalence and impact of nocturnal enuresis and
      overactive bladder (OAB) symptomatology in the adult sickle-cell disease (SCD)
      population. METHODS: We performed a single-center, cross-sectional study of adult
      SCD patients from October 2012 to February 2014, using the validated Pfizer OAB
      short form questionnaire and brief voiding history surveys. Patient responses and
      scores were compared to that of controls having normal or sickle cell trait
      hemoglobin genotypes. RESULTS: A group of 239 SCD patients (116 males, 123
      females) were compared with 104 normal and 57 sickle cell trait patients. Seven
      of 239 (2.9%) SCD patients compared to none of the 161 patients without SCD (P =
      0.04) reported current nocturnal enuresis. The median age of nocturnal enuresis
      cessation was higher in SCD patients (12.0, IQR 9.0-15.0 years) compared to that
      of both normal (7.5, IQR 6.0-9.8 years) and sickle cell trait (7.5, IQR 6.0-8.8
      years) groups (P < 0.0001). Ninety-three of 239 (38.9%) SCD patients compared to
      17 of 104 (16.3%) normal and 11 of 57 (19.3%) sickle cell trait had scores
      indicating OAB symptomatology (P < 0.0001). Patients with SCD had higher OAB
      symptom severity and lower health-related quality of life (HRQL) scores compared
      to the normal and sickle cell trait groups (P < 0.0001 and P < 0.0001,
      respectively). CONCLUSIONS: We demonstrate an elevated rate of nocturnal enuresis
      and OAB symptoms in the adult SCD population. An OAB phenotype may be an under
      recognized complication of SCD irrespective of age. Neurourol. Urodynam. 35:642
      646, 2016. (c) 2015 Wiley Periodicals, Inc.

PMID- 25871446
TI  - Nonenzymatic Transformation of Amorphous CaCO3 into Calcium Phosphate Mineral
      after Exposure to Sodium Phosphate in Vitro: Implications for in Vivo
      Hydroxyapatite Bone Formation.
AB  - Studies indicate that mammalian bone formation is initiated at calcium carbonate
      bioseeds, a process that is driven enzymatically by carbonic anhydrase (CA). We
      show that amorphous calcium carbonate (ACC) and bicarbonate (HCO3 (-) ) cause
      induction of expression of the CA in human osteogenic SaOS-2 cells. The mineral
      deposits formed on the surface of the cells are rich in C, Ca and P. FTIR
      analysis revealed that ACC, vaterite, and aragonite, after exposure to phosphate,
      undergo transformation into calcium phosphate. This exchange was not seen for
      calcite. The changes to ACC, vaterite, and aragonite depended on the
      concentration of phosphate. The rate of incorporation of phosphate into ACC,
      vaterite, and aragonite, is significantly accelerated in the presence of a
      peptide rich in aspartic acid and glutamic acid. We propose that the initial
      CaCO3 bioseed formation is driven by CA, and that the subsequent conversion to
      calcium phosphate/calcium hydroxyapatite (exchange of carbonate by phosphate) is
      a non-enzymatic exchange process. 

PMID- 25871448
TI  - Electronic and Steric Influences of Pendant Amine Groups on the Protonation of
      Molybdenum Bis(dinitrogen) Complexes.
AB  - The synthesis of a series of P(Et)P(NRR(')) (P(Et)P(NRR(')) =
      Et2PCH2CH2P(CH2NRR')2, R = H, R' = Ph or 2,4-difluorophenyl; R = R' = Ph or
      (i)Pr) diphosphine ligands containing mono- and disubstituted pendant amine
      groups and the preparation of their corresponding molybdenum bis(dinitrogen)
      complexes trans-Mo(N2)2(PMePh2)2(P(Et)P(NRR('))) is described. In situ IR and
      multinuclear NMR spectroscopic studies monitoring the stepwise addition of
      triflic acid (HOTf) to trans-Mo(N2)2(PMePh2)2(P(Et)P(NRR('))) complexes in
      tetrahydrofuran at -40  degrees C show that the electronic and steric properties
      of the R and R' groups of the pendant amines influence whether the complexes are
      protonated at Mo, a pendant amine, a coordinated N2 ligand, or a combination of
      these sites. For example, complexes containing monoaryl-substituted pendant
      amines are protonated at Mo and the pendant amine site to generate mono- and
      dicationic Mo-H species. Protonation of the complex containing less basic
      diphenyl-substituted pendant amines exclusively generates a monocationic
      hydrazido (Mo(NNH2)) product, indicating preferential protonation of an N2
      ligand. Addition of HOTf to the complex featuring more basic diisopropyl amines
      primarily produces a monocationic product protonated at a pendant amine site, as
      well as a trace amount of dicationic Mo(NNH2) product that is additionally
      protonated at a pendant amine site. In addition, trans-Mo(N2)2(PMePh2)2(depe)
      (depe = Et2PCH2CH2PEt2) was synthesized to serve as a counterpart lacking pendant
      amines. Treatment of this complex with HOTf generated a monocationic Mo(NNH2)
      product. Protonolysis experiments conducted on several complexes in this study
      afforded trace amounts of NH4(+). Computational analysis of trans
      Mo(N2)2(PMePh2)2(P(Et)P(NRR('))) complexes provides further insight into the
      proton affinity values of the metal center, N2 ligand, and pendant amine sites to
      rationalize differences in their reactivity profiles. 

PMID- 25871447
TI  - Gender differences in the effect of tobacco use on brain phosphocreatine levels
      in methamphetamine-dependent subjects.
AB  - BACKGROUND: A high prevalence of tobacco smoking has been observed in
      methamphetamine users, but there have been no in vivo brain neurochemistry
      studies addressing gender effects of tobacco smoking in methamphetamine users.
      Methamphetamine addiction is associated with increased risk of depression and
      anxiety in females. There is increasing evidence that selective analogues of
      nicotine, a principal active component of tobacco smoking, may ease depression
      and improve cognitive performance in animals and humans. OBJECTIVES: To
      investigate the effects of tobacco smoking and gender on brain phosphocreatine
      (PCr) levels, a marker of brain energy metabolism reported to be reduced in
      methamphetamine-dependent subjects. METHODS: Thirty female and 27 male
      methamphetamine-dependent subjects were evaluated with phosphorus-31 magnetic
      resonance spectroscopy ((31)P-MRS) to measure PCr levels within the pregenual
      anterior cingulate, which has been implicated in methamphetamine neurotoxicity.
      RESULTS: Analysis of covariance revealed that there were statistically
      significant slope (PCr versus lifetime amount of tobacco smoking) differences
      between female and male methamphetamine-dependent subjects (p = 0.03). In
      females, there was also a statistically significant interaction between lifetime
      amounts of tobacco smoking and methamphetamine in regard to PCr levels (p =
      0.01), which suggests that tobacco smoking may have a more significant positive
      impact on brain PCr levels in heavy, as opposed to light to moderate,
      methamphetamine-dependent females. CONCLUSION: These results indicate that
      tobacco smoking has gender-specific effects in terms of increased anterior
      cingulate high energy PCr levels in methamphetamine-dependent subjects. Cigarette
      smoking in methamphetamine-dependent women, particularly those with heavy
      methamphetamine use, may have a potentially protective effect upon neuronal
      metabolism.

PMID- 25871449
TI  - The blood clotting Factor XIIIa forms unique complexes with amyloid-beta (Abeta)
      and colocalizes with deposited Abeta in cerebral amyloid angiopathy.
AB  - AIMS: Cerebral amyloid angiopathy (CAA) is a key pathological hallmark of
      Alzheimer's disease (AD) characterized by accumulation of amyloid-beta (Abeta)
      protein in blood vessel walls. CAA impairs vessel functioning, affects blood
      brain barrier integrity and accelerates cognitive decline of AD patients.
      Unfortunately, mechanisms underlying Abeta deposition in the vessel wall remain
      largely unknown. Factor XIIIa (FXIIIa) is a blood-derived transglutaminase
      crucial in blood coagulation by cross-linking fibrin molecules. Evidence is
      mounting that blood-derived factors are present in CAA and may play a role in
      protein deposition in the vessel wall. We therefore investigated whether FXIIIa
      is present in CAA and if FXIIIa cross-link activity affects Abeta aggregation.
      METHODS: Using immunohistochemistry, we investigated the distribution of FXIIIa,
      its activator thrombin and in situ FXIIIa activity in CAA in post-mortem AD
      tissue. We used surface plasmon resonance and Western blot analysis to study
      binding of FXIIIa to Abeta and the formation of FXIIIa-Abeta complexes,
      respectively. In addition, we studied cytotoxicity of FXIIIa-Abeta complexes to
      cerebrovascular cells. RESULTS: FXIIIa, thrombin and in situ FXIIIa activity
      colocalize with the Abeta deposition in CAA. Furthermore, FXIIIa binds to Abeta
      with a higher binding affinity for Abeta1-42 compared with Abeta1-40 . Moreover,
      highly stable FXIIIa-Abeta complexes are formed independently of FXIIIa cross
      linking activity that protected cerebrovascular cells from Abeta-induced toxicity
      in vitro. CONCLUSIONS: Our data showed that FXIIIa colocalizes with Abeta in CAA
      and that FXIIIa forms unique protein complexes with Abeta that might play an
      important role in Abeta deposition and persistence in the vessel wall.

PMID- 25871450
TI  - Determination of Hydrogen Bond Structure in Water versus Aprotic Environments To
      Test the Relationship Between Length and Stability.
AB  - Hydrogen bonds profoundly influence the architecture and activity of biological
      macromolecules. Deep appreciation of hydrogen bond contributions to biomolecular
      function thus requires a detailed understanding of hydrogen bond structure and
      energetics and the relationship between these properties. Hydrogen bond formation
      energies (DeltaGf) are enormously more favorable in aprotic solvents than in
      water, and two classes of contributing factors have been proposed to explain this
      energetic difference, focusing respectively on the isolated and hydrogen-bonded
      species: (I) water stabilizes the dissociated donor and acceptor groups much
      better than aprotic solvents, thereby reducing the driving force for hydrogen
      bond formation; and (II) water lengthens hydrogen bonds compared to aprotic
      environments, thereby decreasing the potential energy within the hydrogen bond.
      Each model has been proposed to provide a dominant contribution to DeltaGf, but
      incisive tests that distinguish the importance of these contributions are
      lacking. Here we directly test the structural basis of model II. Neutron
      crystallography, NMR spectroscopy, and quantum mechanical calculations
      demonstrate that O-H...O hydrogen bonds in crystals, chloroform, acetone, and
      water have nearly identical lengths and very similar potential energy surfaces
      despite DeltaGf differences >8 kcal/mol across these solvents. These results rule
      out a substantial contribution from solvent-dependent differences in hydrogen
      bond structure and potential energy after association (model II) and thus support
      the conclusion that differences in hydrogen bond DeltaGf are predominantly
      determined by solvent interactions with the dissociated groups (model I). These
      findings advance our understanding of universal hydrogen-bonding interactions and
      have important implications for biology and engineering. 

PMID- 25871451
TI  - An investigation of the association of the H558R polymorphism of the SCN5A gene
      with idiopathic cardiac conduction disorders.
AB  - AIM: The aim of this study was to investigate the predictive value of the
      rs1805124 polymorphism of the SCN5A gene with regard to idiopathic cardiac
      conduction disorders. RESULTS: The AG genotype frequency was significantly higher
      in patients with an atrioventricular block (61,2%+/-6,0%) compared with healthy
      control subjects (34,8%+/-2,3%), p<0.0001. The AG genotype frequencies among
      patients with only idiopathic complete right bundle-branch block (CRBBB) (54,2%+/
      5,5%) and those with both CLBBB and LAH (50%+/-5,1) were significantly higher
      than in the control group (34,8%+/-2,3%), p<0.005. CONCLUSIONS: The AG genotype
      of the H558R (rs1805124) polymorphism of the SCN5A gene is a genetic predictor of
      idiopathic disorders of atrioventricular and intraventricular conduction.

PMID- 25871452
TI  - Dual response to human papilloma virus vaccine in an immunodeficiency disorder:
      resolution of plantar warts and persistence of condylomas.

PMID- 25871457
TI  - Diels-Alders adducts of C60 and esters of 3-(1-indenyl)-propionic acid:
      alternatives for [60]PCBM in polymer:fullerene solar cells.
AB  - A series of new, easily synthesized C60-fullerene derivatives is introduced that
      allow for optimization of the interactions between rr-P3HT and the fullerene by
      systematic variation of the size of the ester group. Two compounds gave overall
      cell efficiencies of 4.8%, clearly outperforming [60]PCBM which gives 4.3% under
      identical conditions. 

PMID- 25871458
TI  - Novel quality indicators for metastatic colorectal cancer management identify
      significant variations in these measures across treatment centers in Australia.
AB  - AIMS: Defining multidisciplinary quality of care indicators (QCIs) for metastatic
      colorectal cancer (mCRC) could improve understanding of variations in routine
      practice care. This may identify areas of below-average performance, which could
      then be addressed by clinicians to improve the quality of care delivered. This
      study aimed to define a panel of QCIs in mCRC and, based on these QCIs, to
      evaluate quality of care across multiple Australian sites. METHODS: A panel of
      clinicians with expertise in colorectal cancer defined evidence-based or best
      practice-based QCIs relevant to the routine multidisciplinary management of mCRC
      patients through structured consensus discussion. Related data were extracted
      from the Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) registry,
      a prospectively maintained database recording comprehensive details on
      consecutive mCRC patients across multiple Australian hospitals. Variations in
      QCIs across sites were explored. RESULTS: Of 13 QCIs defined, data related to 10
      were reliably extracted from TRACC. Analysis of data on 1276 patients across 10
      sites demonstrated low rates of screening for hereditary nonpolyposis colorectal
      cancer in young patients and significant variation in surveillance-detected
      recurrences, lung resection rates and palliative chemotherapy use. Exploratory
      analyses suggested correlation between liver resection rates and survival.
      CONCLUSIONS: We have defined a novel set of mCRC QCIs and have demonstrated wide
      variation in the quality of care of mCRC across multiple Australian sites. With
      further validation to confirm a direct correlation between QCI and patient
      outcomes, these QCIs could be applied to improve the quality of care received by
      all mCRC patients.

PMID- 25871459
TI  - Modular degradable hydrogels based on thiol-reactive oxanorbornadiene linkers.
AB  - Oxanorbornadiene dicarboxylate (OND) reagents are potent Michael acceptors, the
      adducts of which undergo fragmentation by retro-Diels-Alder reaction at rates
      that vary with the substitution pattern on the OND moiety. Rapid conjugate
      addition between thiol-terminated tetravalent PEG and multivalent ONDs yielded
      self-supporting hydrogels within 1 min at physiological temperature and pH.
      Erosion of representative hydrogel formulations occurred with predictable and pH
      independent rates on the order of minutes to weeks. These materials could be made
      non-degradable by epoxidation of the OND linkers without slowing gelation.
      Hydrogels prepared with OND linkers of equal valence had comparable physical
      properties, as determined by equilibrium swelling behavior, indicating similar
      internal network structure. Diffusion and release of entrained cargo varied with
      both the rate of degradation of PEG-OND hydrogels and the hydrodynamic radius of
      the entrained species. These results highlight the utility of OND linkers in the
      preparation of degradable network materials with potential applications in
      sustained release. 

PMID- 25871460
TI  - Polyethylene glycol and divalent salt-induced DNA reentrant condensation revealed
      by single molecule measurements.
AB  - In this study, we investigated the DNA condensation induced by polyethylene
      glycol (PEG) with different molecular weights (PEG 600 and PEG 6000) in the
      presence of NaCl or MgCl2 by using magnetic tweezers (MT) and atomic force
      microscopy (AFM). The MT measurements show that with increasing NaCl
      concentration, the critical condensation force in the PEG 600-DNA or PEG 6000-DNA
      system increased approximately linearly. PEG 6000 solution has a larger critical
      force than PEG 600 solution at a given NaCl concentration. In comparison, a
      parabolic trend of the critical condensation force was observed with increasing
      MgCl2 concentration, indicating that DNA undergoes a reentrant condensation. The
      AFM results show that the morphologies of the compacted DNA-PEG complexes
      depended on the salt concentration and were consistent with the MT results. 

PMID- 25871461
TI  - Optimized synthesis of a tert-butyl-phenyl-substituted tetrapyridophenazine
      ligand and its Ru(II) complexes and determination of dimerization behaviour of
      the complexes through supramolecular "Fingerhakel".
AB  - The synthesis of tpphz(tbp)2 (tpphz(tbp)2 = 3,16-di(tert-butyl-phenyl)
      tetrapyrido[3,2-a:2',3'-c:3'',2''-h:2''',3'''-j]phenazine) has been optimized by
      using a new synthetic route. The complexes Ru(tbp)2tpphz, Rutpphz(tbp)2,
      Rutpphz(tbp)2Ru and the reference compound Ru(tbp)2phen (where Ru = (tbbpy)2Ru,
      tbbpy = 4,4'-di-tert-butyl-2,2'-bipyridine and (tbp)2phen = 3,8-bis(4-tert-butyl
      phenyl)-1,10-phenanthroline) have been synthesized and characterized. Crystal
      structures or structural motifs could be obtained for each intermediate and
      complex and for the first time a tpphz based uncomplexed ligand could be
      investigated in the solid state. The mononuclear complexes Ru(tbp)2tpphz and
      Rutpphz(tbp)2 form pi-pi stacked dimers in the solid state. The latter exhibits
      an interesting aggregation in the solid state with three pi-interactions.
      Concentration dependent aggregation of these isomers in solution is observed with
      the aid of 1H-NMR investigations. Out of those dimerization constants (KD) could
      be calculated for the complexes Ru(tbp)2tpphz and Rutpphz(tbp)2. The values
      differ significantly. Photophysical and electrochemical properties of the
      presented complexes were investigated and compared with reference compounds. The
      tert-butyl-phenyl-substitution induces a stabilization of the 1MLCT and 3MLCT
      states localized on the phenanthroline part of the bridging ligand. The 3MLCT
      localized on the phenazine portion seems to be not or only to a minor extent
      influenced by these substituents.

PMID- 25871462
TI  - Supportive therapy for schizophrenia.
AB  - BACKGROUND: Supportive therapy is often used in everyday clinical care and in
      evaluative studies of other treatments. OBJECTIVES: To review the effects of
      supportive therapy compared with standard care, or other treatments in addition
      to standard care for people with schizophrenia. SEARCH METHODS: For this update,
      we searched the Cochrane Schizophrenia Group's register of trials (November
      2012). SELECTION CRITERIA: All randomised trials involving people with
      schizophrenia and comparing supportive therapy with any other treatment or
      standard care. DATA COLLECTION AND ANALYSIS: We reliably selected studies,
      quality rated these and extracted data. For dichotomous data, we estimated the
      risk ratio (RR) using a fixed-effect model with 95% confidence intervals (CIs).
      Where possible, we undertook intention-to-treat analyses. For continuous data, we
      estimated the mean difference (MD) fixed-effect with 95% CIs. We estimated
      heterogeneity (I(2) technique) and publication bias. We used GRADE to rate
      quality of evidence. MAIN RESULTS: Four new trials were added after the 2012
      search. The review now includes 24 relevant studies, with 2126 participants.
      Overall, the evidence was very low quality.We found no significant differences in
      the primary outcomes of relapse, hospitalisation and general functioning between
      supportive therapy and standard care.There were, however, significant differences
      favouring other psychological or psychosocial treatments over supportive therapy.
      These included hospitalisation rates (4 RCTs, n = 306, RR 1.82 CI 1.11 to 2.99,
      very low quality of evidence), clinical improvement in mental state (3 RCTs, n =
      194, RR 1.27 CI 1.04 to 1.54, very low quality of evidence) and satisfaction of
      treatment for the recipient of care (1 RCT, n = 45, RR 3.19 CI 1.01 to 10.7, very
      low quality of evidence). For this comparison, we found no evidence of
      significant differences for rate of relapse, leaving the study early and quality
      of life.When we compared supportive therapy to cognitive behavioural therapy
      CBT), we again found no significant differences in primary outcomes. There were
      very limited data to compare supportive therapy with family therapy and
      psychoeducation, and no studies provided data regarding clinically important
      change in general functioning, one of our primary outcomes of interest. AUTHORS'
      CONCLUSIONS: There are insufficient data to identify a difference in outcome
      between supportive therapy and standard care. There are several outcomes,
      including hospitalisation and general mental state, indicating advantages for
      other psychological therapies over supportive therapy but these findings are
      based on a few small studies where we graded the evidence as very low quality.
      Future research would benefit from larger trials that use supportive therapy as
      the main treatment arm rather than the comparator.

PMID- 25871464
TI  - An Investigation of the Asymptomatic Limb in Unilateral Lateral Epicondylalgia.
AB  - INTRODUCTION: Musculoskeletal ultrasound (MSUS) imaging is used to investigate
      features of tendinosis. Recent studies have reported tendon pathology not only in
      the symptomatic tendon but also in the contralateral asymptomatic tendon of
      animals and humans with unilateral Achilles tendinopathy. This study assessed the
      symptomatic and contralateral asymptomatic tendon in unilateral lateral
      epicondylalgia (LE) for features of tendinosis and compared with a pain-free
      control. METHODS: Twenty-nine participants with clinically diagnosed unilateral
      LE and 32 pain-free controls (matched for age, sex, and arm dominance) underwent
      a blinded bilateral MSUS examination of the common extensor tendon using a
      standardized protocol. Grayscale features, including tendon thickening,
      hypoechoic region, fibrillar disruption and calcification, as well as
      neovascularity, were scored using separate ordinal scales. Tendon thickness and
      hypoechoic volume were also measured. RESULTS: The contralateral asymptomatic
      tendon did not differ from the tendons of the pain-free controls. The symptomatic
      tendon of participants with LE revealed a significantly greater score for the
      following: tendon thickening (mean difference, 0.76 (95% confidence interval,
      0.22-1.30)), hypoechoic changes (0.58 (0.05-1.11)), fibrillar disruption (0.97
      (0.52-1.42)), and neovascularity (1.53 (0.9-2.2)) than controls. Hypoechoic
      volume was greater in the symptomatic arm (33.0 mm3 (8.4-57.6)), than that in the
      controls. DISCUSSION: Unlike Achilles tendinopathy, MSUS examination did not
      reveal features of tendinosis in the contralateral asymptomatic limb beyond those
      present in tendons of pain-free controls.

PMID- 25871463
TI  - Do observers like curvature or do they dislike angularity?
AB  - Humans have a preference for curved over angular shapes, an effect noted by
      artists as well as scientists. It may be that people like smooth curves or that
      people dislike angles, or both. We investigated this phenomenon in four
      experiments. Using abstract shapes differing in type of contour (angular vs.
      curved) and complexity, Experiment 1 confirmed a preference for curvature not
      linked to perceived complexity. Experiment 2 tested whether the effect was
      modulated by distance. If angular shapes are associated with a threat, the effect
      may be stronger when they are presented within peripersonal space. This
      hypothesis was not supported. Experiment 3 tested whether preference for curves
      occurs when curved lines are compared to straight lines without angles. Sets of
      coloured lines (angular vs. curved vs. straight) were seen through a circular or
      square aperture. Curved lines were liked more than either angular or straight
      lines. Therefore, angles are not necessary to generate a preference for curved
      shapes. Finally, Experiment 4 used an implicit measure of preference, the manikin
      task, to measure approach/avoidance behaviour. Results did not confirm a pattern
      of avoidance for angularity but only a pattern of approach for curvature. Our
      experiments suggest that the threat association hypothesis cannot fully explain
      the curvature effect and that curved shapes are, per se, visually pleasant. 

PMID- 25871465
TI  - Exertion Testing in Youth with Mild Traumatic Brain Injury/Concussion.
AB  - PURPOSE: The decision regarding return to activity (RTA) after mild traumatic
      brain injuries/concussion is one of the most difficult and controversial areas in
      concussion management, particularly for youth. This study investigated how youth
      with postconcussion syndrome (PCS) are affected by exertion and whether
      standardized exertion testing using the McMaster All-Out Progressive Continuous
      Cycling Test can contribute to clinical decision making for safe RTA. METHODS:
      Fifty-four youth (8.5-18.3 yr) with a previously confirmed concussion
      participated in the study. Each participant performed exertion testing on a cycle
      ergometer and completed a Postconcussion Symptom scale at the following time
      points: before exertion (baseline), 5 and 30 min, and 24 h after exertion. A
      modified Postconcussion Symptom scale was administered at 2-min intervals during
      exertion. RESULTS: Participants had a mean +/- SD symptom duration of 6.3 +/- 6.9
      months after the most recent concussive injury, with a median of 4.1 months
      (range, 0.7-35 months). Sixty-three percent of participants had symptoms during
      exertion testing. Symptom profile (number and severity) significantly affected
      perception of exertion at 50% peak mechanical power. During acute assessment of
      symptoms (30-min after exertion), headache (P = 0.39), nausea (P = 0.63), and
      dizziness (P = 0.35) did not change. However, both the number and severity of
      symptoms significantly improved over 24 h, with 56.8% of youth showing
      improvements. The time from the most recent injury had a significant effect on
      the symptom score at baseline, 30 min after exertion, and 24 h after exertion.
      CONCLUSIONS: Exertion testing has an important role in the evaluation of symptoms
      and readiness to RTA, particularly in youth who are slow to recover. Overall,
      controlled exertion seemed to lesson symptoms for most youth.

PMID- 25871466
TI  - Concussion Frequency Associates with Musculoskeletal Injury in Retired NFL
      Players.
AB  - OBJECTIVE: Concussion is commonly associated with immediate and persistent
      alterations in motor function affecting postural control and gait. Patients with
      lower extremity joint injury have demonstrated functional alterations in the
      cerebral cortex, suggesting that musculoskeletal injury may be linked to
      alterations in brain function. Therefore, we examined the associations between
      concussion frequency and lower extremity musculoskeletal injury sustained during
      professional careers of National Football League (NFL) players in a cross
      sectional study. METHODS: An inclusive health history survey was mailed to 3647
      NFL players who retired during 1930-2001. Respondents reported total concussion
      frequency (zero, one, two, or three or more) and presence (yes/no) of specific
      knee and ankle musculoskeletal injury during their NFL career. Separate logistic
      regression models were used to estimate associations between concussion frequency
      and each musculoskeletal injury type, adjusting for number of years played in the
      NFL, body mass index while playing in the NFL, and playing position. RESULTS:
      Data from 2429 players (66.6% response rate) were available for analysis. Nearly
      61% reported experiencing a concussion while competing in the NFL. Meniscal tear
      was the most commonly reported musculoskeletal injury (32%). Compared with NFL
      players who did not sustain a concussion, retired NFL players with one, two, or
      three or more concussions had between 18% and 63%, 15% and 126%, and 73% and 165%
      higher odds of reporting various musculoskeletal injuries, respectively.
      CONCLUSIONS: A history of concussions was associated with a history of
      musculoskeletal injuries during NFL careers. These data suggest that a higher
      number of concussions is linked with higher odds of reporting a musculoskeletal
      injury.

PMID- 25871467
TI  - Salivary duct carcinoma: the predominance of apocrine morphology, prevalence of
      histologic variants, and androgen receptor expression.
AB  - Salivary duct carcinoma (SDC) is a prototypic aggressive salivary gland
      carcinoma. Our aim is to determine the prevalence of histologic variants
      (micropapillary, basal-like) and androgen receptor (AR) expression in a large
      multi-institutional series of SDC. AR status was determined by
      immunohistochemistry (IHC). Most SDCs were characterized by an apocrine phenotype
      and AR expression. Cases with a nonapocrine phenotype and AR-negative status were
      studied by additional IHC and fluorescence in situ hybridization for ETV6 or
      MYB/NFIB. The diagnosis of SDC was confirmed in 187 of 199 (94%) cases. Variant
      morphologies were identified in 12 cases: micropapillary (n=6), sarcomatoid
      (n=3), mucinous (n=2), and basal-like (n=1). AR IHC was performed in 183 cases,
      of which 179 (97.8%) showed AR expression. On the basis of morphologic appearance
      and results of additional studies, 12 cases were reclassified as squamous cell
      carcinoma (SCC) (n=4), epithelial-myoepithelial carcinoma with high-grade
      transformation (HGT) (n=2), myoepithelial carcinoma (n=2), mammary analogue
      secretory carcinoma, high grade (ETV6 translocated; n=1), adenoid cystic
      carcinoma with HGT (n=1), acinic cell carcinoma with HGT (n=1), and adenosquamous
      carcinoma (n=1). AR-negative SDC is extremely rare, and the majority of such
      cases are more accurately classified as other entities. HGTs of other salivary
      carcinomas and squamous cell carcinoma are the most common mimics of SDC. SDCs
      with variant morphologies still show at least a minor component of conventional
      apocrine appearance. Thus, apocrine morphology defines SDC. 

PMID- 25871468
TI  - BAP1-inactivated spitzoid naevi.

PMID- 25871469
TI  - Cyclin D1 does not distinguish YWHAE-NUTM2 high-grade endometrial stromal sarcoma
      from undifferentiated endometrial carcinoma.

PMID- 25871470
TI  - Metastatic prostate adenocarcinoma to the penis presenting as pagetoid carcinoma:
      a phenomenon not previously reported.

PMID- 25871471
TI  - Visual attention in a visual-haptic, cross-modal matching task in children and
      adults.
AB  - Visual fixation patterns were analyzed to gain insight into developmental changes
      in attention allocation in a cross-modal task. Two patterns that have been
      associated with increased task difficulty, gaze aversion and fixation duration,
      were recorded using an eye-tracker. In this exploratory study, 37 elementary age
      children (M age 7-10 yr.) and 23 undergraduates engaged in visual-only and haptic
      visual shape-matching tasks. Theoretical assumptions underlying this study are
      that children have greater limitations on attention capacity compared to adults,
      and that a task presented in the cross-modal condition would pose special demands
      on this capacity. A 2*2 (uni- or cross-modal*age group) repeated-measures
      analysis of variance (ANOVA) was used to analyze both gaze aversion and average
      fixation duration. Children averted gaze significantly more during the cross
      modal condition, supporting the idea that children use gaze aversion as an
      attention-shifting mechanism. Mean fixation duration increased for both groups in
      the cross-modal condition. Due to the small number and limited age range of the
      children as well as the limited number of task items, interpretations are made
      with caution.

PMID- 25871472
TI  - Maturity-related differences in moderate, vigorous, and moderate-to-vigorous
      physical activity in 10-14-year-old boys.
AB  - The goal of this study was to investigate differences in physical activity (PA)
      levels between early, average, and late maturing boys and the effect of
      chronological age, body mass index, and fat mass. PA was measured by
      accelerometry in 10-14-yr.-old boys (N=265) during seven consecutive days.
      Biological maturation groups (early, average, and late) were created. Average and
      late maturing boys had significantly higher moderate PA and moderate-to-vigorous
      PA compared to early maturing boys. Late maturers also had higher vigorous PA
      compared to early maturers. Differences in moderate PA and moderate-to-vigorous
      PA remained significant after controlling for chronological age; however, after
      controlling for Body Mass Index or fat mass the differences were no longer
      significant. Mean differences in PA between early, average, and late maturing
      boys are not independent of Body Mass Index or fat mass. Vigorous PA differences
      between maturity groups were not independent of chronological age.

PMID- 25871473
TI  - AMPK-mediated energy homeostasis and associated metabolic effects on cancer cell
      response and resistance to cetuximab.
AB  - We previously reported that cetuximab, an EGFR-blocking antibody, inhibits cancer
      metabolism via downregulation of HIF-1alpha and reverses the Warburg effect in
      cancer cells. Here, we report that inhibition of HIF-1 transcriptional activity
      by cetuximab does not necessarily lead to successful inhibition of cell
      proliferation. In several head and neck squamous cell carcinoma (HNSCC) cell
      lines, we observed a pattern of oscillating decrease and increase of
      intracellular ATP level after cetuximab treatment, and the magnitude and kinetics
      of which varied by cell line and appeared to be linked to the extent of cellular
      response to cetuximab. In HNSCC cells with low basal level of AMPK activity and
      that responded to cetuximab-induced growth inhibition, there was a transient,
      LKB1-dependent activation of AMPK. In contrast, HNSCC cells that had a high basal
      level of AMPK activity were less sensitive to cetuximab-induced growth inhibition
      despite effective inhibition of EGFR downstream signaling by cetuximab. Knockdown
      or inhibition of AMPK markedly enhanced response to cetuximab via induction of
      apoptosis. These findings indicate that a transient activation of AMPK is an
      early metabolic marker of cellular response to cetuximab and that high and
      sustained AMPK activity is an important mechanism by which cancer cells survive
      cetuximab treatment. 

PMID- 25871474
TI  - LncRNA-ATB promotes trastuzumab resistance and invasion-metastasis cascade in
      breast cancer.
AB  - Trastuzumab resistance is leading cause of mortality in HER2-positive breast
      cancers, and the role of TGF-beta-induced epithelial-mesenchymal transition (EMT)
      in trastuzumab resistance is well established, but the involvement of lncRNAs in
      trastuzumab resistance is still unknown. Here, we generated trastuzumab-resistant
      breast cancer cells with increased invasiveness compared with parental cells, and
      observed robust epithelial-mesenchymal transition (EMT) and consistently elevated
      TGF-beta signaling in these cells. We identified long noncoding RNA activated by
      TGF-beta (lnc-ATB) was the most remarkably upregulated lncRNA in TR SKBR-3 cells
      and the tissues of TR breast cancer patients. We found that lnc-ATB could promote
      trastuzumab resistance and invasion-metastasis cascade in breast cancer by
      competitively biding miR-200c, up-regulating ZEB1 and ZNF-217, and then inducing
      EMT. In addition, we also found that the high level of lnc-ATB was correlated
      with trastuzumab resistance of breast cancer patients. Thus, these findings
      suggest that lncRNA-ATB, a mediator of TGF-beta signaling, could predispose
      breast cancer patients to EMT and trastuzumab resistance. 

PMID- 25871475
TI  - Pygopus-2 promotes invasion and metastasis of hepatic carcinoma cell by
      decreasing E-cadherin expression.
AB  - Pygopus-2 over-expression has been reported in several malignancies, such as
      ovarian, breast, lung and liver cancers. Here we demonstrated that down
      regulation of Pygopus-2 by shRNA inhibited hepatic carcinoma cell invasion in
      vitro and metastasis in xenograft tumor models, which were promoted when Pygopus
      2 was over-expressed. Pygopus-2 increased hepatic carcinoma cell invasion and
      metastasis, by decreasing E-cadherin. Pygopus-2 could bind to the E-cadherin
      promoter, increasing its methylation, and also indirectly decreased zeb2
      expression. In turn these effects caused down-regulation of E-cadherin,
      potentiating invasion and metastasis. We suggest that targeting Pygopus-2 may
      potentially inhibit metastasis of hepatic carcinoma. 

PMID- 25871476
TI  - Claudin-4 is required for vasculogenic mimicry formation in human breast cancer
      cells.
AB  - Vasculogenic mimicry (VM) refers to the unique capability of aggressive tumor
      cells to mimic the pattern of embryonic vasculogenic networks. Claudins are
      aberrantly expressed in aggressive breast cancer. However, the relationship
      between claudins and VM formation is not clear. We examined VM in two human
      breast cancer cell lines with different aggressive capabilities (MDA-MB-231 and
      MCF-7 cells) and one human umbilical vein endothelial cell line (HUVEC). Both
      HUVEC and MDA-MB-231 cells formed vascular channels in Matrigel cultures, while
      MCF-7 cells did not. Western blot analysis revealed a possible correlation
      between claudin-4 and -6 expression in breast cancer cell lines and tumor
      aggressiveness, with protein levels correlating with the ability to form vascular
      channels. Treatment of MDA-MB-231 and HUVEC cells with claudin-4 monoclonal
      antibodies completely inhibited the ability of cells to form vascular channels.
      Moreover, knockdown of claudin-4 by short hairpin RNA completely inhibited tubule
      formation in MDA-MB-231 cells. Overexpression of claudin-4 in MCF-7 cells induced
      formation of vascular channels. Immunocytochemistry revealed that membranous
      claudin-4 protein was significantly associated with vascular channel formation.
      Collectively, these results indicate that claudin-4 may play a critical role in
      VM in human breast cancer cells, opening new opportunities to improve aggressive
      breast cancer therapy. 

PMID- 25871478
TI  - Asymmetric Synthesis of Substituted anti-beta-Fluorophenylalanines.
AB  - A range of substituted anti-beta-fluorophenylalanines was produced from the
      corresponding enantiopure alpha-hydroxy-beta-amino esters using a stereospecific
      XtalFluor-E promoted rearrangement procedure as the key step. The requisite
      substrates are readily produced via aminohydroxylation of an alpha,beta
      unsaturated ester using our lithium amide conjugate addition methodology and,
      following rearrangement, deprotection of the resultant enantiopure beta-fluoro
      alpha-amino esters gives the corresponding enantiopure anti-beta
      fluorophenylalanines in good yield and high diastereoisomeric purity. 

PMID- 25871477
TI  - Expression of programmed cell death ligand 1 (PD-L1) and prevalence of tumor
      infiltrating lymphocytes (TILs) in chordoma.
AB  - Chordomas are primary malignant tumors of the notochord that are resistant to
      conventional chemotherapy. Expression of programmed cell death ligand 1 (PD-L1),
      prevalence of tumor-infiltrating lymphocytes (TILs), and their clinical relevance
      in chordoma remain unknown. We evaluated PD-L1 expression in three chordoma cell
      lines and nine chordoma tissue samples by western blot. Immunohistochemical
      staining was performed on a chordoma tissue microarray (TMA) that contained 78
      tissue specimens. We also correlated the expression of PD-L1 and TILs with
      clinical outcomes. PD-L1 protein expression was demonstrated to be induced by IFN
      gamma in both UCH1 and UCH2 cell lines. Across nine human chordoma tissue
      samples, PD-L1 protein was differentially expressed. 94.9% of chordoma samples
      showed positive PD-L1 expression in the TMA. The expression score of PD-L1 for
      metastatic chordoma tumors was significant higher as compared with non-metastatic
      chordoma tumors. Expression of PD-L1 protein significantly correlates with the
      presence of elevated TILs, which correlates with metastasis. In summary, our
      study showed high levels of PD-L1 are expressed in chordoma, which is correlated
      with the prevalence of TILs. The current study suggests targeting PD-L1 may be a
      novel immunotherapeutic strategy for chordoma clinical trials. 

PMID- 25871480
TI  - HIV/AIDS, the erosion of social capital and the collapse of rural livelihoods in
      the Nkomazi district of South Africa.
AB  - HIV/AIDS is a major driver of livelihood insecurity. The AIDS epidemic, through
      the death or disability of economically productive adults, destabilises and
      erodes the social networks which sustain the livelihoods of vulnerable
      households. This paper draws upon research with home-based care workers and
      family members of 14 households directly affected by HIV/AIDS in the rural
      district of Nkomazi, South Africa. Through a social capital framework this study
      reveals the fragile linkages between households and broader kin networks
      demonstrating the (in)ability of the households to adapt and manage the economic
      and social impact of the epidemic. The chronic financial burden of the epidemic
      on poor households compounded by HIV/AIDS-related stigma undermines kinship ties
      resulting in the extended family becoming more conditional, temporary and at
      times destructive. The extended family cannot be romanticised as a 'safety net'
      and instead needs to be problematised for its complexities, limitations and
      constraints while ensuring sufficient external support is provided to sustain the
      care and support provided by the family and local community. 

PMID- 25871479
TI  - Graded hypoxia and blood oxidative stress during exercise recovery.
AB  - Altitude exposure and exercise elicit oxidative stress in blood; however,
      exercise recovery at 5000 m attenuates oxidative stress. The purpose was to
      determine the altitude threshold at which blood oxidative stress is blunted
      during exercise recovery. Twelve males 18-28 years performed four-cycle ergometry
      bouts (60 min, 70% VO2max, at 975 m). In a randomised counterbalanced crossover
      design, participants recovered 6 h at 0, 1667, 3333 and 5000 m in a normobaric
      hypoxia chamber (recovery altitudes were simulated by using a computerised system
      in an environmental chamber by lowering the partial pressure of oxygen to match
      that of the respective altitude). Oxygen saturation was monitored throughout
      exercise recovery. Blood samples obtained pre-, post-, 1 h post- and 5 h post
      exercise were assayed for ferric-reducing antioxidant plasma, Trolox equivalent
      antioxidant capacity, uric acid, lipid hydroperoxides and protein carbonyls.
      Muscle biopsies obtained pre and 6 h were analysed by real-time polymerase chain
      reaction to quantify expression of hemeoxgenase 1, superoxide dismutase 2 and
      nuclear factor (euthyroid-derived 2)-like factor. Pulse oximetry data were
      similar during exercise, but decreased for the three highest recovery elevations
      (0 m = 0%, 1667 m = -3%; 3333 m = -7%; 5000 m = -17%). A time-dependent oxidative
      stress occurred following exercise for all variables, but the two highest
      recovery altitudes partially attenuated the lipid hydroperoxide response (0 m =
      +135%, 1667 m = +251%, 3333 m = +99%; 5000 m = +108%). Data may indicate an
      altitude threshold between 1667 and 3333 m, above which the oxidative stress
      response is blunted during exercise recovery.

PMID- 25871481
TI  - HIV testing is associated with increased knowledge and reductions in sexual risk
      behaviours among men in Cape Town, South Africa.
AB  - HIV testing benefits those who test positive, allowing them to receive treatment,
      but the benefits for those who test negative remain controversial. We evaluated
      the impact of testing on HIV knowledge and sexual risk among men in South Africa.
      Men were recruited from townships outside Cape Town and completed a survey that
      assessed testing history, knowledge, and sexual behaviours. Among the 820
      participants, 516 (63%) reported being tested (82% tested negative, 6% tested
      positive, and 12% unknown). Compared to those who had never been tested for HIV,
      men who tested for HIV were more knowledgeable about HIV transmission, but did
      not differ on sexual risk behaviour. Knowledge moderated the effect of testing on
      sexual risk such that men reported fewer sexual partners (incidence rate ratio
      (IRR) = 0.91, 95% CI = 0.84, 0.98) and fewer unprotected anal sex events (IRR =
      0.81, 95% CI = 0.66, 1.00) if they had been tested for HIV and were knowledgeable
      about HIV transmission. For men testing HIV-negative, knowledge predicted fewer
      sexual risk behaviours. Previous HIV testing is associated with enhanced
      knowledge, which moderates sexual risk behaviour among South African men living
      in Cape Town. Results suggest that HIV testing may increase knowledge and lead to
      reductions in sexual risk even when results are negative. 

PMID- 25871482
TI  - HIV/AIDS patient satisfaction with a food assistance programme in Sofala
      province, Mozambique.
AB  - Food insecurity is one of the main factors affecting access and adherence to
      antiretroviral treatment (ART) in middle- and low-income countries. To mitigate
      this problem, food assistance interventions are being integrated in ART
      programmes. As evidence of effectiveness of these interventions has been mixed,
      evaluating their implementation is important. We measured the satisfaction of
      HIV/AIDS patients with a food assistance programme in Sofala province in
      Mozambique. This was an observational study that used a combination of
      qualitative and quantitative methods. HIV/AIDS patients receiving food assistance
      took part in focus group discussions (FDGs) and completed a semi-structured
      questionnaire about their opinions about the programme. Data were analysed using
      content and factor analysis, percentages of the maximum attainable scores (PMAS)
      and regression. Patients were satisfied with food assistance and rated it well
      above 60% of PMAS. Four factors were identified as underlying factors of
      satisfaction with food assistance. From these factors, patients were satisfied
      with 2, product availability and the distribution process, and rated these above
      60%. They were dissatisfied with the other 2, quantity of products and the
      enrolment period, and rated these below 60%. From the four factors, only the
      distribution process was significantly associated with satisfaction with food
      assistance (p = 0.001). Satisfaction and the helpfulness of food assistance in
      adherence to ART, as perceived by patients, were significantly associated (p <
      0.001). Patients were satisfied with food assistance. Programme managers should
      focus on the distribution process, quantity of products and enrolment period to
      further improve satisfaction of patients receiving food assistance. 

PMID- 25871483
TI  - Advice dilemmas: Managing advice against the competing public health and
      counselling imperatives that shape VCT in South Africa.
AB  - The public health and counselling imperatives that shape VCT create advice
      dilemmas for counsellors. Public health proponents view the dispensing of advice
      as important, whilst most contemporary counselling dictates that advice should
      not be given under any circumstances. Using a qualitative, discursive approach
      transcripts of twenty-seven videotaped simulated VCT sessions in South Africa
      were analysed with a view to understanding how counsellors implemented advice in
      their daily practice and the discursive strategies they used to do so. The
      results show that counsellors generally struggled to adhere to the dictates of
      both public health and counselling. In managing their advice-dilemmas,
      counsellors either tagged an open-ended question to the end of a directive advice
      statement, or told clients what to do but softened these with client-centred
      skills. As a dual-identified encounter, the role of advice in VCT needs to be
      clarified. Key to resolving this issue is an acknowledgement that, whether as
      counsellor or health adviser, persuasion and influence are central features of
      the VCT interaction. Clear practice guidelines and tools are required to assist
      counsellors to distinguish between advice, suggestion or mere confirmation of an
      intended client action, and the circumstances under which these would be
      recommended or not. 

PMID- 25871484
TI  - Migration status, reproductive health knowledge and sexual behaviour among female
      out-of-school adolescents in Iwaya community, Lagos, Nigeria.
AB  - Reproductive health is an essential aspect of the wellbeing of adolescents.
      Therefore reproductive health knowledge and sexual behaviour deservedly attract
      the attention of researchers, programme planners and policy implementers working
      with young people. Yet in Nigeria, little is known about the effect of migration
      status on reproductive health knowledge and sexual activities of young people in
      general and out-of-school adolescent girls in particular. This study used data
      from a survey of 480 out-of-school adolescent girls to provide empirical answers
      to these puzzles. The results indicated that migrants were less knowledgeable
      about HIV and AIDS but were as poorly aware of methods of contraceptives as non
      migrants. The observed differentials had no significant effect on sexual
      practices such as involvement in penetrative sexual intercourse and multiple
      sexual partnerships. The study concluded that migration status is a major basis
      for social exclusion in the study population and recommends more inclusive
      approaches in the implementation of reproductive health programmes. 

PMID- 25871485
TI  - Just jokes! Icebreakers, innuendo, teasing and talking: The role of humour in
      HIV/AIDS peer education among university students.
AB  - Peer conversation provides an important platform for people to explore and
      disseminate sexual health knowledge. Humour forms part of conversations held
      between peers including those where sexual health and sexual decisions are
      discussed. The central argument of this article links conversation, humour and
      peer education. Drawing on interviews and diaries kept by 12 student peer
      educators over a two-month period in a South African university, the article
      explores the forms and functions of humour in instigating and encouraging
      informal peer education between young people in a university setting. The
      evidence shows that humour can foster intimacy, familiarity and camaraderie in
      peer interactions; keeps conversation moving; and acts as a gateway to discussion
      of taboo, personal and private subjects that lie at the core of effective peer
      education. Components of humour (joking, teasing, innuendo, provocation) and the
      transformation of the serious (and boring) into the enjoyable (and accessible)
      are found in these peer interactions. However, humour can also limit
      communication by keeping conversations light and superficial or, in the case of
      inappropriate humour, close conversation altogether. Acknowledging the nuances of
      humour within conversation and peer education allows for a clearer understanding
      of the ways in which humour contributes to effective health promotion efforts and
      how it can be used within peer educator practice. The effect of the personality
      traits of peer educators on effective use of humour in conversation is an area
      that could benefit from further insight and research. 

PMID- 25871486
TI  - Emerging therapeutic options in age-related macular degeneration.
AB  - Intravitreal injection of anti-VEGF drugs currently represents the standard of
      treatment for exudative age-related macular degeneration. Several therapeutic
      options including steroids, inhibitors of complement factors, anti-platelet
      derived growth factor agents, new anti-VEGF drugs, designed ankyrin repeat
      proteins, sustained drug delivery devices as an alternative to intravitreal
      injections and encapsulated cell technology are the objects of several studies
      and trials worldwide in association with anti-VEGF therapy or not. Expectations
      are that such efforts will help overcome limitations of current therapy with anti
      VEGF, extending the duration of effects and hopefully contributing to the
      regression of neovascular lesions.

PMID- 25871487
TI  - Medical Reasoning with Rough-Set Influence Diagrams.
AB  - There are several advantages to evaluating a problem using influence diagram
      operations. The analyst can use a representation that is natural to the decision
      maker, since the algorithm executes all of the inference and analysis
      automatically. The influence diagram solution procedure can also result in
      significant gains in efficiency. Conditional independence is clearly exhibited in
      the diagram, so the size of intermediate calculations can be reduced, resulting
      in considerable reductions in both processing time and memory requirements.
      However, when imprecise knowledge from data sets is involved in the systems, how
      to reason from approximate information becomes a main issue in evaluating
      influence diagrams effectively. This study develops an alternative knowledge
      model, rough-set influence diagrams (RSID), which combine rough-set decision
      rules and graphical structures of influence diagrams in medical settings. The
      proposed RSID provides a comprehensive schema for knowledge representation and
      decision support. 

PMID- 25871488
TI  - Genetic Variation of MT-ND Genes in Frontotemporal Lobar Degeneration:
      Biochemical Phenotype-Genotype Correlation.
AB  - BACKGROUND: Frontotemporal lobar degeneration (FTLD) is the second most common
      early-onset dementia. Over the last few decades, a growing number of evidence
      suggests mitochondrial involvement in neurodegeneration, namely modifications of
      mitochondrial DNA (mtDNA) contributing to energy impairment. OBJECTIVE: To
      sequence the 7 mitochondrially encoded complex I (MT-ND) genes in 70 FTLD
      patients and investigate mitochondrial respiratory chain (MRC) complex I
      activity. METHODS: A sample of 70 patients was studied (39 females and 31 males;
      age range: 38-82 years, mean +/- SD: 63 +/- 11 years) with a probable diagnosis
      of FTLD. Total DNA was extracted from peripheral blood, and sequencing analysis
      of 7 MT-NDn (1, 2, 3, 4L, 4, 5, 6) genes was performed. Variants identified were
      submitted to in silico study. Spectrophotometric evaluation of MRC activity in
      lymphocytes was performed, and results were compared with age-matched controls.
      RESULTS: A total of 358 (161 different) alterations were found in 92.9% of
      patients. According to in silico analysis of nonsynonymous variants, only 5
      variations are possibly or probably damaging. Complex I activity is significantly
      decreased in patients. CONCLUSION: To our knowledge, this is the first report of
      the complete sequence of the MT-ND genes in FTLD patients and correlation with
      MRC activity. The high number of mtDNA variations identified and a significant
      decrease in complex I activity suggest a possible involvement of mtDNA
      alterations in FTLD. Although the majority of these alterations are not primarily
      pathogenic, an interaction with other mutations may occur, leading to the
      disease, worsening its expression or influencing age of onset.

PMID- 25871490
TI  - Carbon-supported Pt-based alloy electrocatalysts for the oxygen reduction
      reaction in polymer electrolyte membrane fuel cells: particle size, shape, and
      composition manipulation and their impact to activity.

PMID- 25871489
TI  - Egg phospholipids and cardiovascular health.
AB  - Eggs are a major source of phospholipids (PL) in the Western diet. Dietary PL
      have emerged as a potential source of bioactive lipids that may have widespread
      effects on pathways related to inflammation, cholesterol metabolism, and high
      density lipoprotein (HDL) function. Based on pre-clinical studies, egg
      phosphatidylcholine (PC) and sphingomyelin appear to regulate cholesterol
      absorption and inflammation. In clinical studies, egg PL intake is associated
      with beneficial changes in biomarkers related to HDL reverse cholesterol
      transport. Recently, egg PC was shown to be a substrate for the generation of
      trimethylamine N-oxide (TMAO), a gut microbe-dependent metabolite associated with
      increased cardiovascular disease (CVD) risk. More research is warranted to
      examine potential serum TMAO responses with chronic egg ingestion and in
      different populations, such as diabetics. In this review, the recent basic
      science, clinical, and epidemiological findings examining egg PL intake and risk
      of CVD are summarized. 

PMID- 25871491
TI  - Societal cost of traumatic brain injury: A comparison of cost-of-injuries related
      to biking with and without helmet use.
AB  - OBJECTIVE: The goal of this study is to determine if a difference in societal
      costs exists from traumatic brain injuries (TBI) in patients who wear helmets
      compared to non-wearers. METHODS: This is a retrospective cost-of-injury study of
      128 patients admitted to the Montreal General Hospital (MGH) following a TBI that
      occurred while cycling between 2007-2011. Information was collected from Quebec
      Trauma Registry. The independent variables collected were socio-demographic,
      helmet status, clinical and neurological patient information. The dependent
      variables evaluated societal costs. RESULTS: The median costs of hospitalization
      were significantly higher (p = 0.037) in the no helmet group ($7246.67 vs.
      $4328.17). No differences in costs were found for inpatient rehabilitation (p =
      0.525), outpatient rehabilitation (p = 0.192), loss of productivity (p = 0.108)
      or death (p = 1.000). Overall, the differences in total societal costs between
      the helmet and no helmet group were not significantly different (p = 0.065).
      However, the median total costs for patients with isolated TBI in the non-helmet
      group ($22, 232.82) was significantly higher (p = 0.045) compared to the helmet
      group ($13, 920.15). CONCLUSION: Cyclists sustaining TBIs who did not wear
      helmets in this study were found to cost society nearly double that of helmeted
      cyclists.

PMID- 25871492
TI  - The characteristics of superficial siderosis and convexity subarachnoid
      hemorrhage and clinical relevance in suspected cerebral amyloid angiopathy.
AB  - BACKGROUND AND AIMS: Systematic studies of superficial siderosis (SS) and
      convexity subarachnoid hemorrhage (cSAH) in patients with suspected cerebral
      amyloid angiopathy (CAA) without lobar intracerebral hemorrhage (ICH) are
      lacking. We sought to determine the potential anatomic correlation between
      SS/cSAH and transient focal neurological episodes (TFNE) and whether SS/cSAH is
      predictor of future cerebral hemorrhagic events in these patients. METHODS: We
      enrolled 90 consecutive patients with suspected CAA (due to the presence of
      strictly lobar microbleeds (CMBs) and/or SS/cSAH) but without the history of
      symptomatic lobar ICH who underwent brain MRI including T2*-weighted, diffusion
      weighted imaging and fluid-attenuated inversion recovery sequences from an
      ongoing single center CAA cohort from 1998 to 2012. Evaluation of SS, cSAH and
      CMBs was performed. Medical records and follow-up information were obtained from
      prospective databases and medical charts. TFNE was defined according to published
      criteria and electroencephalogram reports were reviewed. RESULTS: Forty-one
      patients (46%) presented with SS and/or cSAH. The prevalence of TFNE was
      significantly higher in those with SS/cSAH (61 vs. 10%; p < 0.001) and
      anatomically correlated with the location of cSAH, but not SS. The majority of
      TFNE in patients with SS/cSAH presented with spreading sensory symptoms.
      Intermittent focal slowing on electroencephalogram was present in the same area
      as SS/cSAH in 6 patients, but no epileptiform activity was found in any patients.
      Among those with available clinical follow-up (76/90 patients, 84%), ten patients
      with SS/cSAH (29%, median time from the scan for all patients with SS/cSAH: 21
      months) had a symptomatic cerebral bleeding event on follow up (average time to
      events: 34 months) compared with only 1 event (2.4%, 25 months from the scan) in
      patients without SS/cSAH (time to event: 25 months) (p = 0.001). The location of
      hemorrhages on follow-up scan was not in the same location of previously noted
      SS/cSAH in 9 of 10 patients. Follow-up imaging was obtained in 9 of 17 patients
      with cSAH and showed evidence of SS in the same location as initial cSAH in all
      these 9 cases. CONCLUSIONS: SS/cSAH is common in patients with suspected CAA
      without lobar intracerebral hemorrhage and may have a significantly higher risk
      of future cerebral bleeding events, regardless of the severity of the baseline
      CMB burden. The findings further highlight a precise anatomical correlation
      between TFNE and cSAH, but not SS. Distinct from transient ischemic attack or
      seizure, the majority of TFNE caused by SS/cSAH appear to present with spreading
      sensory symptoms.

PMID- 25871493
TI  - Bicamphor: a prototypic molecular system to investigate vibrational excitons.
AB  - Vibrational circular dichroism (VCD) and IR spectra have been recorded in the
      fingerprint and carbonyl stretching regions for endo,endo-bicamphor (1), exo,exo
      bicamphor (2), endo,exo-bicamphor (3), 3,3'-bicamphorylidene (4), and exo,exo-bis
      thiocamphor (5). The C2 symmetry possessed by these molecular systems (except in
      one case), as well as their limited conformational mobility associated with well
      defined degrees of freedom, allow for optimal test of the vibrational circular
      dichroism exciton chirality (VCDEC) rule introduced by Taniguchi and Monde.
      Density functional theory calculations are employed not only to predict the
      entire aspect of the VCD and IR spectra but also to study how the VCDEC rule may
      be impacted by the coupling between C?O stretchings and from C?O stretchings with
      other vibrational modes and by the rotation about the C-C bond connecting the two
      camphors. Comments are provided about the limitations and potentialities of the
      VCDEC method and about the manifestation of different vibrational excitons in
      other regions of the VCD spectra, either in the mid-IR or in the CH-stretching
      regions. 

PMID- 25871494
TI  - Teaching health care providers to provide spiritual care: a pilot study.
AB  - BACKGROUND: Health care providers' lack of education on spiritual care is a
      significant barrier to the integration of spiritual care into health care
      services. OBJECTIVE: The study objective was to describe the training program,
      Clinical Pastoral Education for Healthcare Providers (CPE-HP) and evaluate its
      impact on providers' spiritual care skills. METHODS: Fifty CPE-HP participants
      completed self-report surveys at baseline and posttraining measuring frequency of
      and confidence in providing religious/spiritual (R/S) care. Four domains were
      assessed: (1) ability and (2) frequency of R/S care provision; (3) comfort using
      religious language; and (4) confidence in providing R/S care. RESULTS: At
      baseline, participants rated their ability to provide R/S care and comfort with
      religious language as "fair." In the previous two weeks, they reported
      approximately two R/S patient conversations, initiated R/S conversations less
      than twice, and prayed with patients less than once. Posttraining participants'
      reported ability to provide spiritual care increased by 33% (p<0.001). Their
      comfort using religious language improved by 29% (p<0.001), and frequency of R/S
      care increased 75% (p<0.001). Participants reported having 61% more (p<0.001) R/S
      conversations and more frequent prayer with patients (95% increase; p<0.001).
      Confidence in providing spiritual care improved by 36% overall, by 20% (p<0.001)
      with religiously concordant patients, and by 43% (p<0.001) with religiously
      discordant patients. CONCLUSIONS: This study suggests that CPE-HP is an effective
      approach for training health care providers in spiritual care. Dissemination of
      this training may improve integration of spiritual care into health care, thereby
      strengthening comprehensive patient-centered care.

PMID- 25871497
TI  - Repeated Cortisol Awakening Response as Predictor of Antidepressant Treatment
      Outcome with Duloxetine.
AB  - BACKGROUND: Despite considerably extended knowledge about the mechanism of action
      of antidepressants, physicians would greatly benefit from reliable biological
      predictors identifying those patients who will respond poorly to a given
      treatment. The aim of the present study was to assess whether repeated testing of
      the cortisol awakening response (CAR) between baseline and after 10 days of
      duloxetine treatment is able to predict antidepressant treatment outcome after 6
      weeks of treatment. METHODS: 12 patients with a major depressive episode were
      treated with duloxetine 90 mg/day for 6 weeks. At baseline and after 10 days of
      duloxetine treatment, the CAR was assessed, and changes between baseline and day
      10 were categorized as improved or unimproved according to the change in cortisol
      area under the concentration-time curve total concentrations. Depression severity
      was assessed with the 21-item Hamilton Depression Rating Scale (HDRS-21).
      RESULTS: Non-remission after 6 weeks of treatment with duloxetine was predicted
      by an unfavourable saliva cortisol change between baseline and 10 days of
      duloxetine treatment. Linear regression analysis revealed that patients with a
      higher decrease in saliva cortisol measures between baseline and 10 days of
      treatment show a higher decrease in HDRS-21 scores. CONCLUSION: Repeated CAR
      during early treatment is a putative predictive marker of antidepressant
      treatment outcome with duloxetine. (c) 2015 S. Karger AG, Basel.

PMID- 25871495
TI  - A significant risk factor for poststroke depression: the depression-related
      subnetwork.
AB  - BACKGROUND: Despite being one of the direct causes of depression, whether stroke
      induced neuroanatomical deterioration actually plays an important role in the
      onset of poststroke depression (PSD) is controversial. We assessed the structural
      basis of PSD, particularly with regard to white matter connectivity. METHODS: We
      evaluated lesion index, fractional anisotropy (FA) reduction and brain structural
      networks and then analyzed whole brain voxel-based lesions and FA maps. To
      understand brain damage in the context of brain connectivity, we used a graph
      theoretical approach. We selected nodes whose degree correlated with the Hamilton
      Rating Scale for Depression score (p < 0.05, false discovery rate-corrected),
      after controlling for age, sex, years of education, lesion size, Mini Mental
      State Examination score and National Institutes of Health Stroke Scale score. We
      used Poisson regression with robust standard errors to assess the contribution of
      the identified network toward poststroke major depression. RESULTS: We included
      116 stroke patients in the study. Fourteen patients (12.1%) had diagnoses of
      major depression and 26 (22.4%) had mild depression. We found that lesions in the
      right insular cortex, left putamen and right superior longitudinal fasciculus as
      well as FA reductions in broader areas were all associated with major depression.
      Seventeen nodes were selected to build the depression-related subnetwork.
      Decreased local efficiency of the subnetwork was a significant risk factor for
      poststroke major depression (relative risk 0.84, 95% confidence interval 0.72
      0.98, p = 0.027). LIMITATIONS: The inability of DTI tractography to process fibre
      crossings may have resulted in inaccurate construction of white matter networks
      and affected statistical findings. CONCLUSION: The present study provides, to our
      knowledge, the first graph theoretical analysis of white matter networks linked
      to poststroke major depression. These findings provide new insights into the
      neuroanatomical substrates of depression that develops after stroke.

PMID- 25871498
TI  - A combination of probiotics and whey proteins enhances anti-obesity effects of
      calcium and dairy products during nutritional energy restriction in aP2-agouti
      transgenic mice.
AB  - Lactobacillus rhamnosus GG, Lactobacillus paracasei TMC0409, Streptococcus
      thermophilus TMC1543 and whey proteins were used to prepare fermented milk. For
      the experiment aP2- agouti transgenic mice were pre-treated with a high
      sucrose/high-fat diet for 6 weeks to induce obesity. The obese mice were fed a
      diet containing 1.2% Ca and either non-fat dried milk (NFDM) or probiotic
      fermented milk (PFM) with nutritional energy restriction for 6 weeks. The animals
      were examined after the treatment for changes in body weight, fat pad weight,
      fatty acid synthase (FAS) activity, lypolysis, the expression levels of genes
      related to lipid metabolism, insulin sensitivity in adipocytes and skeletal
      muscle and the presence of biomarkers for oxidative and inflammatory stress in
      plasma. It was found that the PFM diet significantly reduced body weight, fat
      accumulation, and adipocyte FAS activity, and increased adipocyte lipolysis as
      compared with the effects of the NFDM diet (P<0.05). The adipose tissue gene
      expression of 11beta-hydroxysteroid dehydrogenase 1 (11beta-HSD1) was
      significantly suppressed in mice that were fed PFM as compared with those that
      were fed NFDM (P<0.05). PFM caused a greater up-regulation of skeletal muscle
      PPARalpha, PPARdelta, uncoupling protein 3 (UCP3) and GLUT4 expression and a
      significant decrease in the plasma concentration of insulin, malondialdehyde, TNF
      alpha, monocyte chemotactic protein-1 and C-reactive protein as compared with the
      effects of NFDM (P<0.05). Fermentation of milk with selected probiotics and
      supplementation of milk with whey proteins may thus enhance anti-obesity effects
      of Ca and dairy products by the suppression of adipose tissue lipogenesis,
      activation of fat oxidation in skeletal muscle and reduction of oxidative and
      inflammatory stress.

PMID- 25871496
TI  - Altered white matter tract property related to impaired focused attention,
      sustained attention, cognitive impulsivity and vigilance in attention-deficit/
      hyperactivity disorder.
AB  - BACKGROUND: The neural substrate for clinical symptoms and neuropsychological
      performance in individuals with attention-deficit/hyperactivity disorder (ADHD)
      has rarely been studied and has yielded inconsistent results. We sought to
      compare the microstructural property of fibre tracts associated with the
      prefrontal cortex and its association with ADHD symptoms and a wide range of
      attention performance in youth with ADHD and healthy controls. METHODS: We
      assessed youths with ADHD and age-, sex-, handedness-, coil- and intelligence
      matched controls using the Conners' Continuous Performance Test (CCPT) for
      attention performance and MRI. The 10 target tracts, including the bilateral
      frontostriatal tracts (caudate to dorsolateral prefrontal cortex, ventrolateral
      prefrontal cortex and orbitofrontal cortex), superior longitudinal fasciculus
      (SLF) and cingulum bundle were reconstructed using diffusion spectrum imaging
      tractography. We computed generalized fractional anisotropy (GFA) values to
      indicate tract-specific microstructural property. RESULTS: We included 50 youths
      with ADHD and 50 healthy controls in our study. Youths with ADHD had lower GFA in
      the left frontostriatal tracts, bilateral SLF and right cingulum bundle and
      performed worse in the CCPT than controls. Furthermore, alteration of the right
      SLF GFA was most significantly associated with the clinical symptom of
      inattention in youths with ADHD. Finally, youths with ADHD had differential
      association patterns of the 10 fibre tract GFA values with attention performance
      compared with controls. LIMITATIONS: Ten of the youths with ADHD were treated
      with methylphenidate, which may have long-term effects on microstructural
      property. CONCLUSION: Our study highlights the importance of the SLF, cingulum
      bundle and frontostriatal tracts for clinical symptoms and attention performance
      in youths with ADHD and demonstrates the involvement of different fibre tracts in
      attention performance in these individuals.

PMID- 25871500
TI  - A systematic study of functionalized oxiranes as initiating groups for cationic
      polycyclization reactions.
AB  - Three different methods have been developed that effectively utilize chiral
      oxiranes derived from Katsuki-Sharpless epoxidation of allylic alcohols as
      initiating groups for cationic cyclization of unsaturated substrates to form
      chiral polycycles. This type of transformation has previously been problematic.
      These employ either epoxy-methoximes, vinyl-substituted oxiranes, or
      hydroxymethyl oxiranes. All three approaches are described in detail. In
      addition, this research has led to possible explanations for previously
      encountered difficulties in this area and provided two new insights into the
      Lewis acid activation of oxiranes. The methodology described herein constitutes a
      valuable link between two powerful synthetic constructions, enantioselective
      Katsuki-Sharpless epoxidation and cationic polycyclization reactions. 

PMID- 25871499
TI  - Association of Transforming Growth Factor Beta-1 (TGF-beta1) Genetic Variation
      with Type 2 Diabetes and End Stage Renal Disease in Two Large Population Samples
      from North India.
AB  - Geographic and ethnic differences impart an immense influence on the genetic
      susceptibility to Type 2 diabetes (T2D) and diabetic nephropathy (DN).
      Transforming growth factor-beta1 (TGF-beta1), a ubiquitously expressed pro
      fibrotic cytokine plays a pivotal role in mediating the hypertrophic and fibrotic
      manifestations of DN. The present study is aimed to study the association of TGF
      beta1 g.869T>C (rs1800470) and g.-509C>T (rs1800469) polymorphism in T2D and end
      stage renal disease (ESRD) cases from the two geographically and ethnically
      different populations from North India. A total of 1313 samples comprising 776
      samples from Punjab (204 with ESRD, 257 without ESRD, and 315 healthy controls)
      and 537 samples from Jammu and Kashmir (150 with ESRD, 187 without ESRD, and 200
      controls) were genotyped for TGF-beta1 (rs1800470 and rs1800469) using ARMS-PCR.
      The CC genotype of rs1800470 increased ESRD risk by 3.1-4.5-fold in both
      populations. However, for rs1800469, the TT genotype provided 5.5-fold risk
      towards ESRD cases from Jammu and Kashmir and no risk for the cases from Punjab.
      The haplotype C-T conferred nearly a 2-3-fold risk towards T2D and ESRD and
      diplotype CC-CT conferred a 4-fold risk towards ESRD. Our results conclude that
      TGF-beta1 (rs1800470) may increase the risk of both ESRD and T2D in both
      populations, but TGF-beta1 (rs1800469) provided risk for only ESRD in the
      population of Jammu and Kashmir. The present study is one of the large sample
      sized genetic association studies of T2D and ESRD from Indian population and adds
      to the scholarship on global health omics. 

PMID- 25871501
TI  - Prognostic value of cardiovascular magnetic resonance derived right ventricular
      function in patients with interstitial lung disease.
AB  - BACKGROUND: Cardiovascular magnetic resonance (CMR) provides non-invasive and
      more accurate assessment of right ventricular (RV) function in comparison to
      echocardiography. Recent study demonstrated that assessment of RV function by
      echocardiography was an independent predictor for mortality in patients with
      interstitial lung disease (ILD). The purpose of this study was to determine the
      prognostic significance of CMR derived RV ejection fraction (RVEF) in ILD
      patients. METHODS: We enrolled 76 patients with ILD and 24 controls in the
      current study. By using 1.5 T CMR scanner equipped with 32 channel cardiac coils,
      we performed steady-state free precession cine CMR to assess the RVEF. RV
      systolic dysfunction (RVSD) was defined as RVEF <=45.0% calculated by long axis
      slices. Pulmonary hypertension (PH) was defined as mean pulmonary artery pressure
      (mPAP) of more than 25 mmHg at rest in the setting of pulmonary capillary wedge
      pressure <=15 mmHg. RESULTS: The median RVEF was 59.2% in controls (n = 24),
      53.8% in ILD patients without PH (n = 42) and 43.1% in ILD patients with PH (n =
      13) (p < 0.001 by one-way ANOVA). During a mean follow-up of 386 days, 18
      patients with RVSD had 11 severe events (3 deaths, 3 right heart failure, 3
      exacerbation of dyspnea requiring oxygen, 2 pneumonia requiring hospitalization).
      In contrast, only 2 exacerbation of dyspnea requiring oxygen were observed in 58
      patients without RVSD. Multivariate Cox regression analysis showed that RVEF
      independently predicted future events, after adjusting for age, sex and RVFAC by
      echocardiography (hazard ratio: 0.889, 95% confidence interval: 0.809-0.976, p =
      0.014). CONCLUSIONS: The current study demonstrated that RVSD in ILD patients can
      be clearly detected by cine CMR. Importantly, low prevalence of PH (17%)
      indicated that population included many mild ILD patients. CMR derived RVEF might
      be useful for the risk stratification and clinical management of ILD patients.

PMID- 25871502
TI  - Visual search is postponed during the period of the AB: An event-related
      potential study.
AB  - In the phenomenon known as the attentional blink (AB), perception of the second
      of two rapidly sequential targets (T2) is impaired when presented shortly after
      the first (T1). Studies in which T2 consisted of a pop-out search array provided
      evidence suggesting that visual search is postponed during the AB. In the present
      work, we used behavioral and electrophysiological measures to test this
      postponement hypothesis. The behavioral measure was reaction time (RT) to T2; the
      electrophysiological measure was the onset latency of an ERP index of attentional
      selection, known as the N2pc. Consistent with the postponement hypothesis, both
      measures were delayed during the AB. The delay in N2pc was substantially shorter
      than that in RT, pointing to multiple sources of delay in the chain of processing
      events, as distinct from the single source postulated in current theories of the
      AB. Finally, the finding that the N2pc was delayed during the AB strongly
      suggests that attention is involved in the processing of pop-out search arrays. 

PMID- 25871503
TI  - Acute intermittent porphyria symptoms during the menstrual cycle.
AB  - BACKGROUND: Acute intermittent porphyria (AIP), a life-threatening form of the
      disease, is accompanied by several pain, mental and physical symptoms. AIMS: In
      this study, we evaluated the cyclicity of AIP and premenstrual syndrome (PMS)
      symptoms in 32 women with DNA-diagnosed AIP during their menstrual cycles, in
      northern Sweden. METHODS: The cyclicity of AIP symptoms and differences in them
      between the follicular and luteal phases, and the cyclicity of each symptom in
      each individual woman in different phases of her menstrual cycle were analysed
      with a prospective daily rating questionnaire. PMS symptoms were also evaluated
      in the patients on a daily rating scale. RESULTS: Of the 32 women, 30 showed
      significant cyclicity in at least one AIP or PMS symptom (P < 0.05-0.001). Back
      pain (10/32) was the most frequent AIP pain symptom and sweet craving (10/15) was
      the most frequent PMS symptom. Pelvic pain (F = 4.823, P = 0.036), irritability
      (F = 7.399, P = 0.011), cheerfulness (F = 5.563, P = 0.025), sexual desire (F =
      8.298, P = 0.007), friendliness (F = 6.157, P = 0.019), breast tenderness (F =
      21.888, P = 0.000) and abdominal swelling (F = 16.982, P = 0.000) showed
      significant cyclicity. Pelvic pain and abdominal swelling (rs = 0.337, P < 0.001)
      showed the strongest correlation. The age of women with latent AIP was strongly
      correlated with abdominal swelling during the luteal phase (rs = 0.493, P <
      0.01). CONCLUSION: Our results suggest that the symptoms of AIP patients change
      during their menstrual cycles.

PMID- 25871504
TI  - Visual-motor integration in children with Prader-Willi syndrome.
AB  - BACKGROUND: Prader-Willi syndrome (PWS) is characterised by hypotonia,
      hypogonadism, short stature, obesity, behavioural problems, intellectual
      disability, and delay in language, social and motor development. There is very
      limited knowledge about visual-motor integration in children with PWS. METHOD:
      Seventy-three children with PWS aged 7-17 years were included. Visual-motor
      integration was assessed using the Beery Visual-motor Integration test at the
      start of the study and after 2 years. The association between visual-motor
      integration and age, gender, genetic subtype and intelligence was assessed.
      RESULTS: Children with PWS scored 'very low' (-3 standard deviations) in visual
      motor integration and 'below average' (-1 standard deviation) in visual
      perception and motor coordination compared with typically developing children.
      Visual-motor integration was higher in children with a deletion (beta = -0.170, P
      = 0.037), in older children (beta = 0.222, P = 0.009) and in those with a higher
      total IQ (beta = 0.784, P < 0.001). Visual perception was higher with a deletion
      (beta = -0.193, P = 0.044) and higher IQ (beta = -0.618, P < 0.001), but motor
      coordination was only higher with a higher total IQ (beta = 0.429, P = 0.001).
      Visual perception and motor coordination were not associated with age or gender.
      There was a trend for visual-motor integration decline over the 2 year follow-up
      period (P = 0.099). Visual perception and motor coordination did not change over
      the follow-up period. CONCLUSIONS: Visual-motor integration is very poor in
      children with PWS. Children scored higher on the time-limited subtests for visual
      perception and motor coordination than the combined test for visual-motor
      integration. Separation of visual-motor integration tasks into pure visual or
      motor tasks and allowing sufficient time to perform the tasks might improve daily
      activities, both at home and at school.

PMID- 25871505
TI  - Ge wetting layer increases ohmic plasmon losses in Ag film due to segregation.
AB  - We have investigated the influence of the Ge wetting layer on both ohmic and
      scattering losses of a surface plasmon-polariton (SPP) wave in Ag film deposited
      on SiO2 substrate with an e-beam evaporator. Samples were examined by means of
      atomic force microscopy (AFM), spectroscopic ellipsometry (SE), two-dimensional X
      ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and microscopic
      four-point probe (M4PP) sheet resistance measurements. Ag films of 100 nm
      thickness were deposited at 180 and 295 K directly onto the substrates with or
      without a Ge interlayer. In AFM scans, we confirm the fact that the commonly used
      Ge adhesion layer smooths the surface of Ag film and therefore reduces scattering
      losses of the SPP wave on surface roughness. However, our ellipsometric
      measurements indicate for the first time that segregation of Ge leads to a
      considerable increase in ohmic losses connected with a boost of the imaginary
      part of Ag permittivity in the 500-800 nm spectral range. Moreover, the trend
      develops over time, as confirmed in a series of measurements performed over an
      interval of three months. XPS analysis confirms the Ge segregation to the Ag free
      surface and most probably to grain boundaries. M4PP measurements show that the
      specific resistivity in Ag films evaporated on a Ge interlayer at 295 K is nearly
      twice as high as in layers deposited directly on a SiO2 substrate. The use of an
      amorphous Al2O3 overlayer prevents Ge segregation to free surface. 

PMID- 25871506
TI  - Extramedullary Hematopoiesis: Cytomorphologic, Histologic, and Radiologic
      Findings in Sixteen Cases.
AB  - BACKGROUND: We report a case series of extramedullary hematopoiesis (EMH)
      diagnosed from the fine needle aspiration (FNA) procedure. Unanticipated EMH is a
      markedly rare diagnosis that typically presents as a solitary mass of
      undetermined significance. As such, knowledge of cytopathologic characteristics
      as well as clinical and radiologic correlates of EMH is paramount. METHOD AND
      MATERIAL: A total of 16 EMH cytopathologic cases were seen at the Johns Hopkins
      Hospital in the past 22 years. RESULTS: Median age at diagnosis was 61 years and
      there was no gender bias (male-to-female ratio: 1:1). Presenting signs and
      symptoms varied widely, from incidental radiographic findings to hemiparesis.
      Likewise, presumptive clinical diagnoses in 11 of the 16 cases were benign and
      the other 5 were considered malignant prior to the diagnostic FNA. The most
      common anatomic site for EMH was the liver, followed by the presacral soft tissue
      and pleura. While most EMH nodules were singular, a few presented with as many as
      three radiographically distinct nodules. The average EMH nodule measured 2.8 cm;
      the EMH liver nodules were larger and measured 4.3 cm on average (p = 0.0043).
      CONCLUSION: We share here the salient clinical and radiologic findings and the
      diagnostic cytopathologic features of EMH in an effort to familiarize the
      pathologist/cytotechnologist community with this fascinating albeit rare entity.

PMID- 25871507
TI  - Plasmonic Hot Electron Induced Photocurrent Response at MoS2-Metal Junctions.
AB  - We investigate the wavelength- and polarization-dependence of photocurrent
      signals generated at few-layer MoS2-metal junctions through spatially resolved
      photocurrent measurements. When incident photon energy is above the direct
      bandgap of few-layer MoS2, the maximum photocurrent response occurs for the light
      polarization direction parallel to the metal electrode edge, which can be
      attributed to photovoltaic effects. In contrast, if incident photon energy is
      below the direct bandgap of MoS2, the photocurrent response is maximized when the
      incident light is polarized in the direction perpendicular to the electrode edge,
      indicating different photocurrent generation mechanisms. Further studies show
      that this polarized photocurrent response can be interpreted in terms of the
      polarized absorption of light by the plasmonic metal electrode, its conversion
      into hot electron-hole pairs, and subsequent injection into MoS2. These
      fundamental studies shed light on the knowledge of photocurrent generation
      mechanisms in metal-semiconductor junctions, opening the door for engineering
      future two-dimensional materials based optoelectronics through surface plasmon
      resonances. 

PMID- 25871508
TI  - Statin reloading before noncardiac surgery: a simple, safe and effective approach
      for reducing the risk of perioperative myocardial infarction.

PMID- 25871509
TI  - One-Year Prospective Study of Community Acquired Influenza and Parainfluenza
      Viral Infections in Hospitalized Egyptian Children with Malignancy: Single Center
      Experience.
AB  - BACKGROUND: Respiratory viruses are widespread in the community and easily
      transmitted to immunocompromised patients. AIMS: Assess the prevalence of
      community-acquired respiratory viral infections among children with cancer
      presenting with clinical picture suggestive of lower respiratory tract infections
      (LRTIs), and evaluate its risk factors and prognosis. METHODS: Over a year, 90
      hospitalized children with malignancy and LRTIs recruited, subjected to clinical
      assessment, investigated through hematology panel, blood culture, chest x-ray, CT
      chest and PCR for influenza A and B, parainfluenza (PIV) types 1 and 3 viruses,
      and respiratory syncytial virus (RSV), and prospectively followed up for the
      clinical outcome. RESULTS: Viral pathogens were identified in 34 patients
      (37.7%), with a seasonal peak from April to May. The most frequently detected
      virus was influenza virus [type A (16 cases; 47%), type B (4 cases; 12%)]
      followed by parainfluenza virus [PIV1 (9 cases; 26%), PIV3 (3 cases; 15%)], and
      none had RSV. Bacteria were identified in 26 patients, fungi in four, mixed
      infections [bacterial/viral and bacterial/fungal] in 13, and 36 cases had
      unidentified etiology. The majority of patients with influenza and parainfluenza
      infections had hematological malignancy, presented with fever, and had mild self
      limited respiratory illness. Five patients with mixed viral and bacterial
      infection had severe symptoms necessitating ICU admission. Six patients died from
      infection-related sequelae; two had mixed PIV and Staphylococcal infections.
      CONCLUSIONS: Community acquired influenza and parainfluenza infections are common
      in pediatrics patients with malignancy, either as isolated or mixed
      viral/bacterial infections. Clinical suspicion is essential as hematological and
      radiological manifestations are nonspecific. Rapid diagnosis and management are
      mandatory to improve patients' outcome.

PMID- 25871510
TI  - Long non coding RNA-UCA1 contributes to cardiomyocyte apoptosis by suppression of
      p27 expression.
AB  - BACKGROUND/AIMS: Urothelial carcinoma-associated 1 (UCA1) is a recently
      identified long non coding RNA (lncRNA). However, few studies have explored its
      role in cardiomyocytes after focal cardiac ischemia reperfusion injury (CIR).
      METHODS: Rat CIR models were established using ligation of the Lower Anterior
      Descending artery (LAD). Cell apoptosis and reactive oxygen species (ROS)
      production in cardiac tissues were explored using immunohistochemistry and DHE
      staining. lncRNA expression patterns were detected using microarray and validated
      by qPCR. Cell viability and apoptosis were examined using MTT assay and flow
      cytometry. RESULTS: CIR significantly induced cell apoptosis and ROS production
      in the rat model. The results of microarray demonstrated the reduced expression
      of UCA1, which was validated by qPCR. Follow-up experiments showed that UCA1 was
      involved in H2O2-induced cell apoptosis. We further showed that UCA1 negatively
      correlated with the expression of p27. Moreover, overexpression of p27 could
      induce primary cardiomyocyte apoptosis. CONCLUSIONS: Reduction of UCA1 levels
      plays a pro-apoptotic role in primary cardiomyocytes partially through
      stimulation of p27 protein expression. These results are in agreement with the
      observed levels of UCA1, p27 and apoptosis after cardiac I/R injury, suggesting
      that UCA1 might have an important role during I/R injury.

PMID- 25871511
TI  - A New Nomenclature of Xenopus laevis Chromosomes Based on the Phylogenetic
      Relationship to Silurana/Xenopus tropicalis.
AB  - Xenopus laevis (XLA) is an allotetraploid species which appears to have undergone
      whole-genome duplication after the interspecific hybridization of 2 diploid
      species closely related to Silurana/Xenopus tropicalis (XTR). Previous cDNA
      fluorescence in situ hybridization (FISH) experiments have identified 9 sets of
      homoeologous chromosomes in X. laevis, in which 8 sets correspond to chromosomes
      1-8 of X. tropicalis (XTR1-XTR8), and the last set corresponds to a fusion of
      XTR9 and XTR10. In addition, recent X. laevis genome sequencing and BAC-FISH
      experiments support this physiological relationship and show no gross chromosome
      translocation in the X. laevis karyotype. Therefore, for the benefit of both
      comparative cytogenetics and genome research, we here propose a new chromosome
      nomenclature for X. laevis based on the phylogenetic relationship and chromosome
      length, i.e. XLA1L, XLA1S, XLA2L, XLA2S, and so on, in which the numbering of XLA
      chromosomes corresponds to that in X. tropicalis and the postfixes 'L' and 'S'
      stand for 'long' and 'short' chromosomes in the homoeologous pairs, which can be
      distinguished cytologically by their relative size. The last chromosome set is
      named XLA9L and XLA9S, in which XLA9 corresponds to both XTR9 and XTR10, and
      hence, to emphasize the phylogenetic relationship to X. tropicalis, XLA9_10L and
      XLA9_10S are also used as synonyms.

PMID- 25871512
TI  - Association of LPHN3 rs6551665 A/G polymorphism with attention deficit and
      hyperactivity disorder in Korean children.
AB  - Attention deficit hyperactivity disorder (ADHD) is a common and highly heritable
      disorder of school-age children. Its heritability was estimated at 80-90% but the
      genetic component underpinning this disorder remains to be disclosed. Recently, a
      highly consistent association between latrophilin3 (LPHN3) gene and ADHD was
      reported. In the present study, we examined the association between the LPHN3
      rs6551665 A/G polymorphism and ADHD in Korea. The samples used in the study
      consisted of 150 ADHD children and 322 controls. The ADHD children were diagnosed
      according to DSM-IV. ADHD symptoms were evaluated with Dupaul Parent ADHD Rating
      Scales. LPHN3 rs6551665 SNP was determined by PCR-RFLP. Hardy-Weinberg
      equilibrium, genotype and allele frequency differences between the case and the
      control, and odds ratio were examined using the chi-square and exact tests. The
      LPHN3 gene locus was found to have no deviation from the Hardy-Weinberg
      expectation. We observed a significant association between the ADHD children and
      control group in genotype frequency (p=0.01) and allele frequency (p=0.02). The
      ADHD children appeared to have a surplus of GG genotype (OR 2.959, 95% CI 1.416
      6.184, p=0.003) and G allele (OR 1.44, 95% CI 1.062-1.945, p=0.02). The
      association was more distinctive when analysis was confined to male samples
      (p=0.005), the OR of male controls and cases was 4.029 (95% CI 1.597-10.164,
      p=0.002) and the OR having G allele vs. A allele was 1.46 (95% CI 1.002-2.127,
      p=0.048). Thus our results imply that the LPHN3 rs6551665 GG genotype and G
      allele may provide a significant effect on the ADHD, although larger sample sizes
      and functional studies are necessary to further elucidate these findings.

PMID- 25871513
TI  - Transcriptomic profiling of peripheral blood CD4+ T-cells in asthmatics with and
      without depression.
AB  - BACKGROUND: Cumulative studies have shown that asthma is associated with
      depression but the underlying mechanisms are poorly understood. This study aimed
      to determine whether asthma with depression is characterized by unique
      pathophysiological pathways by analyzing the global gene expression patterns of
      CD4(+) T-cells from asthmatics with or without depression. MATERIALS AND METHODS:
      Four groups of subjects (non-depressive asthmatics, depressive asthmatics,
      depression patients, and healthy controls) consisting of 6 participants in each
      group were studied. Peripheral CD4(+) T-cells were isolated and the global
      transcriptomic profiles were defined by using the Agilent SurePrint G3 Human GE
      8x60K microarray. The differences in transcriptomic profiles between asthma with
      or without depression, depression patients and healthy controls were examined.
      Pathway enrichment analyses of differentially expressed genes were performed
      using the Ingenuity Pathway Analysis. Selected genes were verified and correlated
      to the clinical characteristics. RESULTS: A total of 1448 differentially
      expressed transcripts were identified in any of the non-depressive asthma vs.
      healthy control, depressive asthma vs. healthy control, or depression vs. healthy
      control comparisons after correction for multiple comparisons. Among these, 156
      were demonstrated as differentially expressed genes only in depressive asthma vs.
      healthy control. Twenty significant biological pathways were identified and were
      involved in inflammation, metabolism, immunity, tumor and cell cycle. Increased
      expression of phosphoinositide-3-kinase, regulatory subunit 1 (alpha) was
      confirmed in depressive asthmatics and it was inversely correlated with lung
      function (FEV1/FVC%). CONCLUSIONS: Asthmatics with depression exhibit unique
      pathophysiological pathways and this result may provide clues for specific
      molecular mechanisms underlying asthma with depression.

PMID- 25871514
TI  - Genome-wide screen of DNA methylation identifies novel markers in childhood
      obesity.
AB  - Epigenetic modifications have been highlighted in chronic non-communicable
      diseases. The aim of this study was to investigate genome-wide DNA methylation
      for the identification of methylation markers in obesity. With obese Chinese
      preschool children, we performed comprehensive DNA methylation profiling of gene
      promoters and CpG islands to determine the differentially methylated genes using
      methylated DNA immunoprecipitation followed by hybridization to the NimbleGen
      Human DNA Methylation 385K Promoter Plus CpG Island Microarray. We found that
      compared to lean children, 251 promoters and 575 CGIs were demethylated, and 141
      promoters and 277 CGIs were hypermethylated in obese children, and their
      distribution on chromosomes was imbalanced, showing more promoters and CGIs with
      demethylation on chromosomes 3, 16, 17 and 19 and more differentially methylated
      promoters and CGIs on chromosome X compared with chromosome Y. Further analysis
      indicated that aberrant methylations occurred mostly in HCP promoters and
      promoter CGIs. Among the top 80 promoters and CGIs that had differentiated
      methylation between obese and lean children, nearly half have been previously
      studied, and almost all of them are involved in the pathogenesis of cancers that
      are associated with many organs. Furthermore, four genes (FZD7, PRLHR, EXOSC4,
      and EIF6) with differential promoter methylation were validated, and their
      associations with obesity must be clarified. In conclusion, this study represents
      the first effort to determine methylation markers in obese Chinese children,
      which has potential relevance for identifying markers that are useful in
      elucidating the mechanisms of obesity pathogenesis and its complications. 

PMID- 25871515
TI  - Association between interleukin 17A polymorphisms and susceptibility to
      rheumatoid arthritis in a Chinese population.
AB  - BACKGROUND: Previous studies have revealed an association between interleukin 17A
      (IL17A) polymorphisms and the prevalence of rheumatoid arthritis (RA) in Japanese
      and Caucasian patients. We hypothesized that IL17A polymorphisms might also
      affect RA susceptibility in the Chinese population. METHODS: We studied IL17A
      rs2275913 G/A, rs3819024 A/G, rs3819025 G/A, rs4711998 A/G, rs8193036 C/T and
      rs8193037 G/A polymorphisms in 615 RA patients and 839 controls in a Chinese
      population. Genotyping was performed using a custom-by-design 48-Plex SNP scanTM
      Kit. RESULTS: Our results indicated that IL17A rs4711998 A/G and IL17A rs8193037
      G/A polymorphisms were not associated with RA, and IL17A rs2275913 G/A and IL17A
      rs3819024 A/G variant alleles decrease the risk of RA, while IL17A rs3819025 G/A
      and IL17A rs8193036 C/T variant alleles increase the risk of RA. CONCLUSIONS:
      These findings suggest that IL17A polymorphisms may be associated with RA. Future
      larger studies with other ethnic populations are required to confirm current
      findings.

PMID- 25871516
TI  - Beta-defensin in Nile tilapia (Oreochromis niloticus): Sequence, tissue
      expression, and anti-bacterial activity of synthetic peptides.
AB  - Beta-defensins (beta-defensins) are small cationic amphiphilic peptides that are
      widely distributed in plants, insects, and vertebrates, and are important for
      their antimicrobial properties. In this study, the beta-defensin (Onbeta
      defensin) gene of the Nile tilapia (Oreochromis niloticus) was cloned from spleen
      tissue. Onbeta-defensin has a genomic DNA sequence of 674 bp and produces a cDNA
      of 454 bp. Sequence alignments showed that Onbeta-defensin contains three exons
      and two introns. Sequence analysis of the cDNA identified an open reading frame
      of 201 bp, encoding 66 amino acids. Bioinformatic analysis showed that Onbeta
      defensin encodes a cytoplasmic protein molecule containing a signal peptide. The
      deduced amino acid sequence of this peptide contains six conserved cysteine
      residues and two conserved glycine residues, and shows 81.82% and 78.33% sequence
      similarities with beta-defensin-1 of fugu (Takifugu rubripes) and rainbow trout
      (Oncorhynchus mykiss), respectively. Real-time quantitative PCR showed that the
      level of Onbeta-defensin expression was highest in the skin (307.1-fold),
      followed by the spleen (77.3-fold), kidney (17.8-fold), and muscle (16.5-fold)
      compared to controls. By contrast, low levels of expression were found in the
      liver, heart, intestine, stomach, and gill (<3.0-fold). Artificial infection of
      tilapia with Streptococcus agalactiae (group B streptococcus [GBS] strain)
      resulted in a significantly upregulated expression of Onbeta-defensin in the
      skin, muscle, kidney, and gill. In vitro antimicrobial experiments showed that a
      synthetic Onbeta-defensin polypeptide had a certain degree of inhibitory effect
      on the growth of Escherichia coli DH5alpha and S. agalactiae. The results
      indicate that Onbeta-defensin plays a role in immune responses that suppress or
      kill pathogens.

PMID- 25871517
TI  - An ultrasensitive gold nanoparticles improved real-time immuno-PCR assay for
      detecting diethyl phthalate in foodstuff samples.
AB  - A specific polyclonal antibody targeting diethyl phthalate (DEP) with the higher
      antibody titer at 1:120,000 has been obtained, and an ultrasensitive and high
      throughput direct competitive gold nanoparticles improved real-time immuno-PCR
      (GNP-rt-IPCR) technique has been developed for detecting DEP in foodstuff
      samples. Under optimal conditions, a rather low linearity is achieved within a
      range of 4 pg L(-1) to 40 ng L(-1), and the limit of detection (LOD) is 1.06 pg
      L(-1). Otherwise, the GNP-rt-IPCR technique is highly selective, with low cross
      reactivity values for DEP analogs (<5%). Finally, the concentrations of DEP in
      foodstuff samples by the GNP-rt-IPCR method range from 0.48 to 41.88 MUg kg(-1).
      Satisfactory recoveries (88.39-112.79%) and coefficient of variation values (8.38
      12.77%) are obtained. The consistency between the results obtained from GNP-rt
      IPCR and gas chromatography-mass spectrometry (GC-MS) is 98.3%, which further
      proves that GNP-rt-IPCR is an accurate, reliable, rapid, ultrasensitive, and high
      throughput method for batch determination of trace amounts of DEP in foodstuff
      samples.

PMID- 25871518
TI  - Interactions of hyaluronic Acid with the skin and implications for the dermal
      delivery of biomacromolecules.
AB  - Hyaluronic acid (HA) hydrogels are interesting delivery systems for topical
      applications. Besides moisturizing the skin and improving wound healing, HA
      facilitates topical drug absorption and is highly compatible with labile
      biomacromolecules. Hence, in this study we investigated the influence of HA
      hydrogels with different molecular weights (5 kDa, 100 kDa, 1 MDa) on the skin
      absorption of the model protein bovine serum albumin (BSA) using fluorescence
      lifetime imaging microscopy (FLIM). To elucidate the interactions of HA with the
      stratum corneum and the skin absorption of HA itself, we combined FLIM and
      Fourier-transform infrared (FTIR) spectroscopy. Our results revealed distinct
      formulation and skin-dependent effects. In barrier deficient (tape-stripped)
      skin, BSA alone penetrated into dermal layers. When BSA and HA were applied
      together, however, penetration was restricted to the epidermis. In normal skin,
      penetration enhancement of BSA into the epidermis was observed when applying low
      molecular weight HA (5 kDa). Fluorescence resonance energy transfer analysis
      indicated close interactions between HA and BSA under these conditions. FTIR
      spectroscopic analysis of HA interactions with stratum corneum constituents
      showed an alpha-helix to beta-sheet interconversion of keratin in the stratum
      corneum, increased skin hydration, and intense interactions between 100 kDa HA
      and the skin lipids resulting in a more disordered arrangement of the latter. In
      conclusion, HA hydrogels restricted the delivery of biomacromolecules to the
      stratum corneum and viable epidermis in barrier deficient skin, and therefore
      seem to be potential topical drug vehicles. In contrast, HA acted as an enhancer
      for delivery in normal skin, probably mediated by a combination of cotransport,
      increased skin hydration, and modifications of the stratum corneum properties. 

PMID- 25871519
TI  - Fibroblast growth factor 21 protects mouse brain against D-galactose induced
      aging via suppression of oxidative stress response and advanced glycation end
      products formation.
AB  - Fibroblast growth factor 21 (FGF21) is a hormone secreted predominantly in the
      liver, pancreas and adipose tissue. Recently, it has been reported that FGF21
      Transgenic mice can extend their lifespan compared with wild type counterparts.
      Thus, we hypothesize that FGF21 may play some roles in aging of organisms. In
      this study d-galactose (d-gal)-induced aging mice were used to study the
      mechanism that FGF21 protects mice from aging. The three-month-old Kunming mice
      were subcutaneously injected with d-gal (180mg.kg(-1).d(-1)) for 8weeks and
      administered simultaneously with FGF21 (1, 2 or 5mg.kg(-1).d(-1)). Our results
      showed that administration of FGF21 significantly improved behavioral performance
      of d-gal-treated mice in water maze task and step-down test, reduced brain cell
      damage in the hippocampus, and attenuated the d-gal-induced production of MDA,
      ROS and advanced glycation end products (AGEs). At the same time, FGF21 also
      markedly renewed the activities of superoxide dismutase (SOD), catalase (CAT),
      glutathione peroxidase (GPx) and total anti-oxidation capability (T-AOC), and
      decreased the enhanced total cholinesterase (TChE) activity in the brain of d-gal
      treated mice. The expression of aldose reductase (AR), sorbitol dehydrogenase
      (SDH) and member-anchored receptor for AGEs (RAGE) declined significantly after
      FGF21 treatment. Furthermore, FGF21 suppressed inflamm-aging by inhibiting
      IkappaBalpha degradation and NF-kappaB p65 nuclear translocation. The expression
      levels of pro-inflammatory cytokines, such as TNF-alpha and IL-6, decreased
      significantly. In conclusion, these results suggest that FGF21 protects the aging
      mice brain from d-gal-induced injury by attenuating oxidative stress damage and
      decreasing AGE formation. 

PMID- 25871520
TI  - Amino acid substitutions contributing to alpha2,6-sialic acid linkage binding
      specificity of human parainfluenza virus type 3 hemagglutinin-neuraminidase.
AB  - Human parainfluenza virus type 3 (hPIV3) recognizes both alpha2,3- and alpha2,6
      linked sialic acids, whereas human parainfluenza virus type 1 (hPIV1) recognizes
      only alpha2,3-linked sialic acids. To identify amino acid residues that confer
      alpha2,6-linked sialic acid recognition of hPIV3, amino acid residues in or
      neighboring the sialic acid binding pocket of the hPIV3 hemagglutinin
      neuraminidase (HN) glycoprotein were substituted for the corresponding residues
      of hPIV1 HN. Hemadsorption assay with sialyl linkage-modified red blood cells
      indicated that amino acid residues at positions 275, 277, 372, and 426 contribute
      to alpha2,6-linked sialic acid recognition of the HN3 glycoprotein. 

PMID- 25871521
TI  - Fluorescence quenching studies of structure and dynamics in calmodulin-eNOS
      complexes.
AB  - Activation of endothelial nitric oxide synthase (eNOS) by calmodulin (CaM)
      facilitates formation of a sequence of conformational states that is not well
      understood. Fluorescence decays of fluorescently labeled CaM bound to eNOS reveal
      four distinct conformational states and single-molecule fluorescence trajectories
      show multiple fluorescence states with transitions between states occurring on
      time scales of milliseconds to seconds. A model is proposed relating fluorescence
      quenching states to enzyme conformations. Specifically, we propose that the most
      highly quenched state corresponds to CaM docked to an oxygenase domain of the
      enzyme. In single-molecule trajectories, this state occurs with time lags
      consistent with the oxygenase activity of the enzyme. 

PMID- 25871522
TI  - Structural and functional characterization of tumor suppressors TIG3 and H
      REV107.
AB  - H-REV107-like family proteins TIG3 and H-REV107 are class II tumor suppressors.
      Here we report that the C-terminal domains (CTDs) of TIG3 and H-REV107 can induce
      HeLa cell death independently. The N-terminal domain (NTD) of TIG3 enhances the
      cell death inducing ability of CTD, while NTD of H-REV107 plays an inhibitory
      role. The solution structure of TIG3 NTD is very similar to that of H-REV107 in
      overall fold. However, the CTD binding regions on NTD are different between TIG3
      and H-REV107, which may explain their functional difference. As a result, the
      flexible main loop of H-REV107, but not that of TIG3, is critical for its NTD to
      modulate its CTD in inducing cell death. 

PMID- 25871523
TI  - Different conformational dynamics of various active states of beta-arrestin1
      analyzed by hydrogen/deuterium exchange mass spectrometry.
AB  - Arrestins have important roles in G protein-coupled receptor (GPCR) signaling
      including desensitization of GPCRs and G protein-independent signaling. Two major
      intra-molecular interactions, the polar core and the three-element region,
      maintain arrestins in the basal conformation by connecting the N- and C-domains.
      Mutations in these regions that disrupt the polar core (R169E or p44) or the
      three-element (3A) have been reported to interact with GPCRs in a phosphorylation
      independent manner, and thus these mutants are referred to as pre-activated
      arrestins. On the other hand, deletion of 7 residues in the linker region between
      N- and C-domains (Delta7) freezes arrestins in the inactive state, which has a
      much lower binding affinity to GPCRs compared to the wild type form. Although
      these mutants are widely used for functional studies of arrestins, the
      conformations of these mutants have not yet been fully elucidated. Here, we
      analyzed the conformational dynamics of beta-arrestin1 with various mutants
      (R169E, p44, 3A, and Delta7) by hydrogen/deuterium exchange mass spectrometry
      (HDX-MS). HDX-MS data revealed that pre-activated mutants have more deuterium
      uptake than the basal state, and also that the regions and degree of increased
      deuterium uptake differ between pre-activated mutants. Unexpectedly, the inactive
      mutant also showed increased deuterium uptake in a few regions. 

PMID- 25871524
TI  - Characterization of the termini of the West Nile virus genome and their
      interactions with the small isoform of the 2' 5'-oligoadenylate synthetase
      family.
AB  - 2' 5'-Oligoadenylate synthetases (OAS) are interferon-stimulated proteins that
      act in the innate immune response to viral infection. Upon binding viral double
      stranded RNA, OAS enzymes produce 2'-5'-linked oligoadenylates that stimulate
      RNase L and ultimately slow viral propagation. Truncations/mutations in the
      smallest human OAS isoform, OAS1, results in susceptibility to West Nile virus
      (WNV). We have previously demonstrated in vitro the interaction between OAS1 and
      the 5'-terminal region of the WNV RNA genome. Here we report that the 3'-terminal
      region is also able to mediate specific interaction with and activation of OAS1.
      Binding and kinetic experiments identified a specific stem loop within the 3'
      terminal region that is sufficient for activation of the enzyme. The solution
      conformation of the 3'-terminal region was determined by small angle X-ray
      scattering, and computational models suggest a conformationally restrained
      structure comprised of a helix and short stem loop. Structural investigation of
      the 3'-terminal region in complex with OAS1 is also presented. Finally, we show
      that genome cyclization by base pairing between the 5'- and 3'-terminal regions,
      a required step for replication, is not sufficient to protect WNV from OAS1
      recognition in vitro. These data provide a physical framework for understanding
      recognition of the highly structured terminal regions of a flaviviral genome by
      an innate immune enzyme. 

PMID- 25871525
TI  - Evaluation of molecular- and culture-dependent MST markers to detect fecal
      contamination and indicate viral presence in good quality groundwater.
AB  - Microbial contamination of groundwater represents a significant health risk to
      resource users. Culture-dependent Bacteroides phage and molecular-dependent
      Bacteroidales 16S rRNA assays are employed in microbial source tracking (MST)
      studies globally, however little is known regarding how these important groups
      relate to each other in the environment and which is more suitable to indicate
      the presence of waterborne fecal pollution and human enteric viruses. This study
      addresses this knowledge gap by examining 64 groundwater samples from sites with
      varying hydrogeological properties using a MST toolbox containing two
      bacteriophage groups (phage infecting GB-124 and ARABA-84), and two Bacteroidales
      16S rRNA markers (Hf183 and BacR); those were compared to fecal indicator
      bacteria, somatic coliphage, Bacteroidales 16S rRNA marker AllBac, four human
      enteric viruses (norovirus GI and II, enterovirus and group A rotavirus) and
      supplementary hydrogeological/chemical data. Bacteroidales 16S rRNA indicators
      offered a more sensitive assessment of both human-specific and general fecal
      contamination than phage indicators, but may overestimate the risk from enteric
      viral pathogens. Comparison with hydrogeological and land use site
      characteristics as well as auxiliary microbiological and chemical data proved the
      plausibility of the MST findings. Sites representing karst aquifers were of
      significantly worse microbial quality than those with unconsolidated or fissured
      aquifers, highlighting the vulnerability of these hydrogeological settings.

PMID- 25871526
TI  - Osseoconductivity of a Specific Streptavidin-Biotin-Fibronectin Surface Coating
      of Biotinylated Titanium Implants - A Rabbit Animal Study.
AB  - BACKGROUND: Biofunctionalized implant surfaces may accelerate bony integration
      and increase long-term stability. PURPOSE: The aim of the study was to evaluate
      the osseous reaction toward biomimetic titanium implants surfaces coated with
      quasicovalent immobilized fibronectin in an in vivo animal model. MATERIALS AND
      METHODS: A total of 84 implants (uncoated [control 1, n = 36], streptavidin
      biotin coated [test 1, n = 24], streptavidin-biotin-fibronectin coated [test 2, n
      = 24]) were inserted 1 mm supracortically in the proximal tibia of 12 rabbits.
      The samples were examined after 3 and 6 weeks. Total bone-implant contact (tBIC;
      %), bone-implant contact in the cortical (cBIC; %) and in the spongious bone
      (sBIC; %) as well as the percentage of linear bone fill (PLF; %) were evaluated.
      RESULTS: After 3 weeks, streptavidin-biotin-fibronectin implants had a
      significant higher sBIC (p = .043) and PLF (p = .007) compared with the uncoated
      samples. After 6 weeks, this difference was significant for tBIC (p = .016) and
      cBIC (p < .001). Additionally, uncoated screws showed a significant higher sBIC
      when compared with the fibronectin coating (p < .001). Streptavidin-biotin-coated
      implants showed less bone growth at both time points of all examined parameters
      when compared with their counterparts (all p < .001). CONCLUSIONS: Quasicovalent
      immobilization of biotinylated fibronectin with the streptavidin-biotin
      fibronectin system on smooth surface titanium shows a beneficial faster osseous
      healing in vivo. Besides, an antifouling effect of the streptavidin-biotin
      coating was proven.

PMID- 25871527
TI  - Probing Conformational Change of Bovine Serum Albumin-Dextran Conjugates under
      Controlled Dry Heating.
AB  - The time-dependent conformational change of bovine serum album (BSA) during
      Maillard reaction with dextran under controlled dry heating has been studied by
      small-angle X-ray scattering, fluorescence spectroscopy, dynamic light
      scattering, and circular dichroism analysis. Through the research on the radii of
      gyration (Rg), intrinsic fluorescence, and secondary structure, conjugates with
      dextran coating were found to inhibit BSA aggregation and preserve the secondary
      structure of native BSA against long-time heat treatment during Maillard
      reaction. The results suggested that the hydrophilic dextran was conjugated to
      the compact protein surface and enclosed it and more dextran chains were attached
      to BSA with the increase of the heating time. The study presented here will be
      beneficial to the understanding of the conformational evolution of BSA molecules
      during the dry-heating Maillard reaction and to the control of the protein
      polysaccharide conjugate structure. 

PMID- 25871528
TI  - Glomerular damage in experimental proliferative glomerulonephritis under
      glomerular capillary hypertension.
AB  - BACKGROUND/AIMS: Immunologically and hemodynamically mediated the destruction of
      glomerular architecture is thought to be the major causes of end-stage renal
      failure. The purpose of this study is to evaluate the effect of glomerular
      hypertension on glomerular injury and the progression of glomerular sclerosis
      after Thy-1 nephritis was induced. METHOD: Thy-1 nephritis was induced in the
      stroke-prone spontaneously hypertensive rat strain (SHR-SP) (group SP) and in age
      matched Wistar-Kyoto (WKY) (group WKY) rats, following unilateral nephrectomy
      (UNX), and a vehicle was injected alone in UNX SHR-SP as control (group SC).
      RESULT: The degree of glomerular damage in response to a single dose of anti-thy
      1 antibody, and its functional consequences (eg. proteinuria, diminished GFR) are
      more pronounced in group SP than normotensive group WKY and hypertensive group SC
      without mesangial cell injury. While normotensive group WKY rats recovered
      completely from mesangial cell injury on day 28-42, glomeruli in group SP kept on
      persistent macrophage infiltration, alpha-SMA expression on day 42-56. In
      addition, glomerular capillary repair with the GECs was rarely seen in
      pronouncedly proliferative and sclerostic areas. The incidence of glomerular
      sclerosis and the level of proteinuria were markedly increased by day 56 in the
      group SP. CONCLUSIONS: Our results demonstrate that glomerular hypertension
      aggravate glomerular damage and glomerulosclerosis in this model of Thy 1
      nephritis.

PMID- 25871529
TI  - Downregulation of lncRNA TUG1 affects apoptosis and insulin secretion in mouse
      pancreatic beta cells.
AB  - BACKGROUND: Increasing evidence indicates that long noncoding RNAs (IncRNAs)
      perform specific biological functions in diverse processes. Recent studies have
      reported that IncRNAs may be involved in beta cell function. The aim of this
      study was to characterize the role of IncRNA TUG1 in mouse pancreatic beta cell
      functioning both in vitro and in vivo. METHODS: qRT-PCR analyses were performed
      to detect the expression of lncRNA TUG1 in different tissues. RNAi, MTT, TUNEL
      and Annexin V-FITC assays and western blot, GSIS, ELISA and immunochemistry
      analyses were performed to detect the effect of lncRNA TUG1 on cell apoptosis and
      insulin secretion in vitro and in vivo. RESULTS: lncRNA TUG1 was highly expressed
      in pancreatic tissue compared with other organ tissues, and expression was
      dynamically regulated by glucose in Nit-1 cells. Knockdown of lncRNA TUG1
      expression resulted in an increased apoptosis ratio and decreased insulin
      secretion in beta cells both in vitro and in vivo . Immunochemistry analyses
      suggested decreased relative islet area after treatment with lncRNA TUG1 siRNA.
      CONCLUSION: Downregulation of lncRNA TUG1 expression affected apoptosis and
      insulin secretion in pancreatic beta cells in vitro and in vivo. lncRNA TUG1 may
      represent a factor that regulates the function of pancreatic beta cells.

PMID- 25871530
TI  - Kinetics of Propargyl Radical Dissociation.
AB  - Due to the prominent role of the propargyl radical for hydrocarbon growth within
      combustion environments, it is important to understand the kinetics of its
      formation and loss. The ab initio transition state theory-based master equation
      method is used to obtain theoretical kinetic predictions for the temperature and
      pressure dependence of the thermal decomposition of propargyl, which may be its
      primary loss channel under some conditions. The potential energy surface for the
      decomposition of propargyl is first mapped at a high level of theory with a
      combination of coupled cluster and multireference perturbation calculations.
      Variational transition state theory is then used to predict the microcanonical
      rate coefficients, which are subsequently implemented within the multiple-well
      multiple-channel master equation. A variety of energy transfer parameters are
      considered, and the sensitivity of the thermal rate predictions to these
      parameters is explored. The predictions for the thermal decomposition rate
      coefficient are found to be in good agreement with the limited experimental data.
      Modified Arrhenius representations of the rate constants are reported for utility
      in combustion modeling. 

PMID- 25871531
TI  - Ethics in Animal-Based Research.
AB  - In recent years, there have been a number of new demands and regulations which
      have reignited the discussion on ethics in animal-based research. In the light of
      this development, the present review first presents an overview of underlying
      core ethical questions and issues. This is followed by an outline of the current
      discussion on whether animals (used for experimentation) should have rights
      ascribed to them and whether animals need to have certain characteristics in
      order to be the beneficiaries of rights. The discourse on concepts of sentience
      and the 'sociozoological scale' in particular is mapped out in this regard. There
      follows an outline of relevant ethical positions and current moral approaches to
      animal-based research (animal rights position, utilitarianism, 'convergence
      position', intrinsic cultural value of fundamental research, 'contractarianism',
      anthropocentrism, principle of the three Rs).

PMID- 25871532
TI  - Subcutaneous dirofilariasis of the eyelid in a 7-month-old infant.
AB  - Human dirofilariasis is an unusual zoonotic infection (transmitted from animals
      to humans) presenting as a subcutaneous nodule. Occasionally it involves the eye.
      The parasite is transmitted to humans by mosquitoes. Presentation in infants is
      extremely rare. A rare case of subcutaneous dirofilariasis of the eyelid in a 7
      month-old infant is reported.

PMID- 25871533
TI  - Unusual presentation of subretinal cysticercosis with hypopyon uveitis.
AB  - Subretinal cysticercosis presenting with anterior uveitis and hypopyon is rare. A
      7-year-old boy presented with pain and hypopyon in the right eye. Ultrasonography
      showed a cystic lesion with scolex. Because visual prognosis was poor, he was
      treated conservatively. Timely diagnosis would facilitate early therapy and
      prevent visual loss.

PMID- 25871535
TI  - Effective host materials for blue/white organic light-emitting diodes by
      utilizing the twisted conjugation structure in 10-phenyl-9,10-dihydroacridine
      block.
AB  - Two new 10-phenyl-9,10-dihydroacridine derivatives attached by dibenzothiophene
      (DBT) and dibenzofuran (DBF) were synthesized. The influence of the substituents
      of these materials was studied by theoretical calculations (DFT calculation) and
      experimental measurements. Owing to the twisted N-phenyl ring, both molecules
      possess sufficiently high triplet energies and are suitable as hosts for
      phosphorescent organic light-emitting diodes. To evaluate the electroluminescent
      (EL) performance of these materials, FIrpic-based blue PHOLEDs and two-color
      white PHOLEDs (FIrpic and PO-01 as the dopants) were fabricated using the common
      device structures. High external quantum efficiencies (EQE) of 21.1 % and 20.9 %
      for FIrpic-based blue PHOLEDs were achieved by FPhAc and TPhAc, respectively. The
      white device based on the host FPhAc achieved a higher performance, with a
      maximum EQE of 24.7 % than the device with TPhAc as host material.

PMID- 25871534
TI  - Substance P promotes wound healing in diabetes by modulating inflammation and
      macrophage phenotype.
AB  - Diabetic foot ulceration is a major complication of diabetes. Substance P (SP) is
      involved in wound healing, but its effect in diabetic skin wounds is unclear. We
      examined the effect of exogenous SP delivery on diabetic mouse and rabbit wounds.
      We also studied the impact of deficiency in SP or its receptor, neurokinin-1
      receptor, on wound healing in mouse models. SP treatment improved wound healing
      in mice and rabbits, whereas the absence of SP or its receptor impaired wound
      progression in mice. Moreover, SP bioavailability in diabetic skin was reduced as
      SP gene expression was decreased, whereas the gene expression and protein levels
      of the enzyme that degrades SP, neutral endopeptidase, were increased. Diabetes
      and SP deficiency were associated with absence of an acute inflammatory response
      important for wound healing progression and instead revealed a persistent
      inflammation throughout the healing process. SP treatment induced an acute
      inflammatory response, which enabled the progression to the proliferative phase
      and modulated macrophage activation toward the M2 phenotype that promotes wound
      healing. In conclusion, SP treatment reverses the chronic proinflammatory state
      in diabetic skin and promotes healing of diabetic wounds.

PMID- 25871536
TI  - Biomimetic gradient scaffold from ice-templating for self-seeding of cells with
      capillary effect.
AB  - One of the most important issues in bone tissue engineering is the search for new
      materials and processing techniques to create novel scaffolds with 3-D porous
      structures. Although many properties such as biodegradability and porosity have
      been considered in designing bone scaffolds, very limited attention is paid to
      their capillary effect. In nature, capillary effect is ubiquitously used by
      plants and animals to constantly transport water and nutrients based on
      morphological and/or chemical gradient structures at multiple length-scales. In
      this work, we developed a modified freeze-casting technique to prepare ceramic
      scaffolds with gradient channel structures. The results show that our
      hydroxyapatite (HA) scaffolds have interconnected gradient channels that mimic
      the porous network of natural bone. More importantly, we demonstrate that such a
      scaffold has a very unique capillary behavior that promotes the self-seeding of
      cells when in contact with a cell solution due to spontaneous capillary flow
      generated from gradient channel structures. The strategy developed here provides
      a new avenue for designing "smart" scaffolds with complex porous structures and
      biological functions that mimic natural tissues. 

PMID- 25871537
TI  - Mechanobiology of mesenchymal stem cells: Perspective into mechanical induction
      of MSC fate.
AB  - Bone marrow-derived mesenchymal stem and stromal cells (MSCs) are promising
      candidates for cell-based therapies in diverse conditions including tissue
      engineering. Advancement of these therapies relies on the ability to direct MSCs
      toward specific cell phenotypes. Despite identification of applied forces that
      affect self-maintenance, proliferation, and differentiation of MSCs, mechanisms
      underlying the integration of mechanically induced signaling cascades and
      interpretation of mechanical signals by MSCs remain elusive. During the past
      decade, many researchers have demonstrated that external applied forces can
      activate osteogenic signaling pathways in MSCs, including Wnt, Ror2, and Runx2.
      Besides, recent advances have highlighted the critical role of internal forces
      due to cell-matrix interaction in MSC function. These internal forces can be
      achieved by the materials that cells reside in through its mechanical properties,
      such as rigidity, topography, degradability, and substrate patterning. MSCs can
      generate contractile forces to sense these mechanical properties and thereby
      perceive mechanical information that directs broad aspects of MSC functions,
      including lineage commitment. Although many signaling pathways have been
      elucidated in material-induced lineage specification of MSCs, discovering the
      mechanisms by which MSCs respond to such cell-generated forces is still
      challenging because of the highly intricate signaling milieu present in MSC
      environment. However, bioengineers are bridging this gap by developing platforms
      to control mechanical cues with improved throughput and precision, thereby
      enabling further investigation of mechanically induced MSC functions. In this
      review, we discuss the most recent advances that how applied forces and cell
      generated forces may be engineered to determine MSC fate, and overview a subset
      of the operative signal transduction mechanisms and experimental platforms that
      have emerged in MSC mechanobiology research. Our main goal is to provide an up-to
      date view of MSC mechanobiology that is relevant to both mechanical loading and
      mechanical properties of the environment, and introduce these emerging platforms
      for tissue engineering use.

PMID- 25871538
TI  - Functionalised nanoscale coatings using layer-by-layer assembly for imparting
      antibacterial properties to polylactide-co-glycolide surfaces.
AB  - In order to achieve high local biological activity and reduce the risk of side
      effects of antibiotics in the treatment of periodontal and bone infections, a
      localised and temporally controlled delivery system is desirable. The aim of this
      research was to develop a functionalised and resorbable surface to contact soft
      tissues to improve the antibacterial behaviour during the first week after its
      implantation in the treatment of periodontal and bone infections. Solvent-cast
      poly(d,l-lactide-co-glycolide acid) (PLGA) films were aminolysed and then
      modified by Layer-by-Layer technique to obtain a nano-layered coating using
      poly(sodium4-styrenesulfonate) (PSS) and poly(allylamine hydrochloride) (PAH) as
      polyelectrolytes. The water-soluble antibiotic, metronidazole (MET), was
      incorporated from the ninth layer. Infrared spectroscopy showed that the PSS and
      PAH absorption bands increased with the layer number. The contact angle values
      had a regular alternate behaviour from the ninth layer. X-ray Photoelectron
      Spectroscopy evidenced two distinct peaks, N1s and S2p, indicating PAH and PSS
      had been introduced. Atomic Force Microscopy showed the presence of
      polyelectrolytes on the surface with a measured roughness about 10nm after 20
      layers' deposition. The drug release was monitored by Ultraviolet-visible
      spectroscopy showing 80% loaded-drug delivery in 14 days. Finally, the
      biocompatibility was evaluated in vitro with L929 mouse fibroblasts and the
      antibacterial properties were demonstrated successfully against the keystone
      periodontal bacteria Porphyromonas gingivalis, which has an influence on implant
      failure, without compromising in vitro biocompatibility. In this study, PLGA was
      successfully modified to obtain a localised and temporally controlled drug
      delivery system, demonstrating the potential value of LbL as a coating technology
      for the manufacture of medical devices with advanced functional properties.

PMID- 25871539
TI  - High concentration of phosphorus is a distinctive feature of myelin. An X-ray
      elemental microanalysis study using freeze-fracture scanning electron microscopy
      of rat sciatic nerve.
AB  - We have used rat sciatic nerves submitted to freezing and freeze-fracture to
      determine the elemental composition of small domains of the peripheral nerve
      studied at high resolution by scanning electron microscopy. We found that myelin
      of Schwann cells is unique in its high content in phosphorus (P) that was more
      than 10 times higher than P measured in any other cells. This high concentration
      in P makes myelin chemistry suitable of monitoring at the subcellular level using
      the herein described methodology.

PMID- 25871540
TI  - Deconins A-E: Cuparenic and Mevalonic or Propionic Acid Conjugates from the
      Basidiomycete Deconica sp. 471.
AB  - Bioassay-guided fractionation of antibacterial extracts from cultures of a
      basidiomycete from Northern Thailand, which represents a new species of the genus
      Deconica, yielded the terpenoid deconin A (1), whose structure was elucidated by
      spectral methods (NMR, HRMS) as a cuparenic/mevalonic acid conjugate. The
      absolute configuration of 1 was determined after saponification and comparison of
      specific rotations of the resulting cuparenic acid and mevalonolactone with
      authentic standards and literature data. Six minor congeners (2-7) were isolated
      and identified, and their antimicrobial and cytotoxic effects are reported.
      Compounds 1-4 are the first natural products featuring an unmodified mevalonic
      acid residue as a building block. 

PMID- 25871541
TI  - The risk of hyponatremia with desmopressin use for nocturnal polyuria.
AB  - BACKGROUND: Desmopressin is used for treating nocturnal polyuria, but
      hyponatremia is an associated concern in the elderly due to impaired urinary
      dilution. This study was undertaken to characterize hyponatremia occurring in
      adults using desmopressin for nocturnal polyuria. METHODS: Data from 172 patients
      who were prescribed desmopressin for nocturnal polyuria at a urology clinic from
      September 2010 through February 2013 were retrospectively analyzed. Demographic
      and laboratory parameters were investigated to examine the risk factors for
      desmopressin-associated hyponatremia. RESULTS: The average follow-up serum sodium
      measured 21 +/- 22 days after using desmopressin was 138 +/- 5 mmol/l.
      Hyponatremia (<135 mmol/l) was found in 24 patients (14%), and it was severe in 7
      (<126 mmol/l). In the hyponatremic patients, serum sodium decreased by 11 +/- 6
      mmol/l. Patients with hyponatremia were older than those with normonatremia (78
      +/- 7 vs. 68 +/- 9 years, p < 0.0001). The presence of either hyponatremia
      predisposing comorbidities or concurrent medications was associated with
      hyponatremia. Patients with hyponatremia had lower basal hemoglobin (11 +/- 2 vs.
      13 +/- 2 g/dl, p < 0.001) and serum sodium (139 +/- 2 vs. 140 +/- 2 mmol/l, p <
      0.05) than those with normonatremia. Multivariate logistic regression after
      adjustment for basal serum sodium showed that advanced age (OR 1.15; 95% CI 1.03
      1.27) and lower hemoglobin level (OR 0.64; 95% CI 0.43-0.94) were independently
      associated with hyponatremia. CONCLUSION: Hyponatremia is not infrequently
      associated with desmopressin use. Those with advanced age (>=65 years) and lower
      hemoglobin are at risk of desmopressin-associated hyponatremia and need to be
      carefully monitored.

PMID- 25871542
TI  - Comparison of the provocative concentration of methacholine causing a 20% fall in
      FEV1 between the AeroEclipse II breath-actuated nebulizer and the wright
      nebulizer in adult subjects with asthma.
AB  - RATIONALE: The American Thoracic Society guidelines for methacholine testing for
      the diagnosis of asthma recommends the 2-minute tidal breathing protocol with the
      Wright nebulizer, which produces more aerosol than required, generates a small
      particle size, and requires cleaning between tests. OBJECTIVES: To evaluate
      methacholine testing using a disposable, breath-actuated AeroEclipse II, which
      produces aerosol during inspiration and was developed for single-patient use.
      METHODS: Forty-six adult subjects with asthma (19 men), aged 27.3 (SD, 9.5)
      years, with FEV1 98.5 (SD, 18.1) % predicted participated in a randomized,
      crossover, observational study. Subjects were first screened using the Wright
      nebulizer, then assigned to 2 minutes of tidal breathing from the Wright or 20
      seconds of tidal breathing from the AeroEclipse nebulizer on 2 separate days, in
      random order. Provocative concentration of methacholine causing a 20% fall in
      FEV1 (PC20) values were calculated by linear interpolation of log dose-versus
      response curves, log-transformed, and compared using paired Student t test and
      Pearson correlation. MEASUREMENTS AND MAIN RESULTS: The 38 subjects demonstrating
      reproducible PC20 measurements of within 1.5 doubling concentrations were
      included in the comparison. The geometric mean methacholine PC20 measured with
      the AeroEclipse nebulizer was approximately 1 doubling concentration lower than
      the geometric mean methacholine PC20 of the Wright nebulizer (P < 0.05). The
      Pearson correlation coefficient between the two nebulizers was 0.86 (P < 0.05).
      CONCLUSIONS: The PC20 measurements using the two nebulizers were highly
      correlated; however, the PC20 determined with the AeroEclipse nebulizer was
      significantly lower than those determined using the Wright nebulizer. Clinical
      trial registered with www.clinicaltrials.gov (NCT 01919424).

PMID- 25871543
TI  - Expression of Malus xiaojinensis IRT1 (MxIRT1) protein in transgenic yeast cells
      leads to degradation through autophagy in the presence of excessive iron.
AB  - Iron is essential for plants, but highly toxic when present in excess.
      Consequently, iron uptake by root transporters must be finely tuned to avoid
      excess uptake from soil under iron excess. The iron-regulated transporter of
      Malus xiaojinensis (MxIRT1), induced in roots under iron deficiency, is a highly
      effective iron(II) transporter. Here, we investigated how the presence of
      excessive iron leads to MxIRT1 degradation in yeast expressing this plant iron
      transporter protein. To determine the relationship between iron abundance and
      MxIRT1 degradation, relative levels of autophagy-related gene-8 (ATG8) mRNA and
      the active ATG8-phosphatidylethanolamine-conjugated (PE) protein were measured in
      wild-type yeast and the autophagic mutant strains atg1?, atg5?, atg7?, ypt7? and
      tor1? under normal and excessive iron conditions. The data showed that the
      exposure of MxIRT1-eGFP-transformed wild-type and tor1? strains to excessive iron
      led to significantly increased levels of ATG8 transcript and ATG8-PE protein,
      which resulted in enhanced MxIRT1 degradation. Co-localization of mCherry-ATG8
      and MxIRT1-eGFP provided evidence that these proteins interact during autophagy
      in yeast. While inhibition of autophagic initiation, autophagosome formation and
      vacuole fusion all decreased MxIRT1 degradation. PMSF inhibition of autophagy
      prevented degradation, leading to the accumulation of MxIRT1-containing vesicles
      in the vacuoles. MxIRT1-vesicles were sorted into autophagosomes for iron-induced
      degradation in yeast, whereas the endogenous iron(II) transporter Fet4 was
      degraded in an autophagy-independent manner. Moreover, immunoprecipitation showed
      that multimono-ubiquitins provided MxIRT1 with the ubiquitination signal.
      Together, three factors, iron excess, autophagy and mono-ubiquitination, affect
      the functional activity and stability of exogenous MxIRT1 in yeast, thereby
      preventing iron uptake via this root transporter.

PMID- 25871544
TI  - Diacylglycerol Metabolism and Signaling Is a Driving Force Underlying FASN
      Inhibitor Sensitivity in Cancer Cells.
AB  - Fatty acid synthase (FASN) generates the de novo source of lipids for cell
      proliferation and is a promising cancer therapy target. Development of FASN
      inhibitors, however, necessitates a better understanding of sensitive and
      resistant cancer types to optimize patient treatment. Indeed, testing the
      cytotoxic effects of FASN inhibition across human cancer cells revealed diverse
      sensitivities. We show here that metabolic incorporation of glucose into specific
      complex lipid species strongly predicts FASN inhibitor sensitivity. We also show
      that the levels of one of these lipid classes, protein kinase C (PKC) stimulator
      diacylglycerols, are lowered upon FASN inhibitor treatment in sensitive compared
      to resistant cells and that PKC activators and inhibitors rescue cell death in
      sensitive cells and sensitize resistant cells, respectively. Our findings not
      only reveal a biomarker for predicting FASN sensitivity in cancer cells but also
      a put forth a heretofore unrecognized mechanism underlying the anticancer effects
      of FASN inhibitors.

PMID- 25871545
TI  - Honokiol blocks and reverses cardiac hypertrophy in mice by activating
      mitochondrial Sirt3.
AB  - Honokiol (HKL) is a natural biphenolic compound derived from the bark of magnolia
      trees with anti-inflammatory, anti-oxidative, anti-tumour and neuroprotective
      properties. Here we show that HKL blocks agonist-induced and pressure overload
      mediated, cardiac hypertrophic responses, and ameliorates pre-existing cardiac
      hypertrophy, in mice. Our data suggest that the anti-hypertrophic effects of HKL
      depend on activation of the deacetylase Sirt3. We demonstrate that HKL is present
      in mitochondria, enhances Sirt3 expression nearly twofold and suggest that HKL
      may bind to Sirt3 to further increase its activity. Increased Sirt3 activity is
      associated with reduced acetylation of mitochondrial Sirt3 substrates, MnSOD and
      oligomycin-sensitivity conferring protein (OSCP). HKL-treatment increases
      mitochondrial rate of oxygen consumption and reduces ROS synthesis in wild type,
      but not in Sirt3-KO cells. Moreover, HKL-treatment blocks cardiac fibroblast
      proliferation and differentiation to myofibroblasts in a Sirt3-dependent manner.
      These results suggest that HKL is a pharmacological activator of Sirt3 capable of
      blocking, and even reversing, the cardiac hypertrophic response. 

PMID- 25871546
TI  - HPV-negative squamous cell carcinoma of the anal canal is unresponsive to
      standard treatment and frequently carries disruptive mutations in TP53.
AB  - BACKGROUND: Human papillomavirus (HPV), p16 expression, and TP53 mutations are
      known prognostic factors in head and neck squamous cell carcinoma, but their role
      in squamous cell carcinoma of the anal canal (SCCAC) is less well established.
      The objective of this study was to determine the prognostic significance of
      tumour HPV status, p16 and p53 expression, and mutations in TP53 in patients with
      SCCAC receiving (chemo)radiotherapy. METHODS: Human papillomavirus DNA was
      determined using an INNO-LiPA-based assay in tumour tissue of 107 patients with
      locally advanced SCCAC. Patients were treated with radiotherapy, with or without
      concurrent chemotherapy consisting of a fluoropyrimidine and mitomycin C.
      Expression of p16 and p53 was determined using immunohistochemistry. Exons 2-11
      of TP53 in tumour tissue were sequenced. RESULTS: DNA of high-risk HPV types was
      detected in 93 out of 107 tumours (87%), all of which overexpressed p16
      (HPV+/p16+). Of 14 HPV-negative (HPV-) tumours (13%), 10 (9%) were p16-negative
      (HPV-/p16-) and 4 (4%) overexpressed p16 (HPV-/p16+). Patients with HPV-/p16-
      disease had inferior 3-year locoregional control (LRC) (15%) compared with
      patients with HPV+/p16+ tumours (82%, P<0.001) and HPV-/p16+ tumours (75%,
      P=0.078). Similarly, 3-year overall survival (OS) was 35% (HPV-/p16-) vs 87%
      (HPV+/p16+, P<0.001) and 75% (HPV-/p16+, P=0.219). Disruptive mutations in TP53
      were found in 80% of HPV-/p16- tumours vs 6% of HPV+/p16+ tumours (P<0.001). In
      multivariate analysis, HPV-/p16- status was an independent predictor of inferior
      LRC and OS. CONCLUSIONS: HPV- tumours are frequently TP53 mutated. HPV-/p16-
      status is a strong predictor for reduced LRC and OS, and alternative treatment
      strategies for patients with HPV-/p16- disease need to be explored.

PMID- 25871548
TI  - Single-Molecule Analyte Recognition with ClyA Nanopores Equipped with Internal
      Protein Adaptors.
AB  - Nanopores have been used to detect molecules, to sequence DNA, or to investigate
      chemical reactions at the single-molecule level. Because they approach the
      absolute limit of sensor miniaturization, nanopores are amenable to
      parallelization and could be used in single-cell measurements. Here we show that
      single enzymes can be functionally and reversibly trapped inside the confined
      space of a ClyA nanopore. Remarkably, the binding of ligands to the internalized
      proteins is mirrored by specific changes to the nanopore conductance.
      Conveniently, the manipulation of the charge of the protein allowed increasing of
      the residence time of the protein inside the nanopore. Nanopores with
      internalized protein adaptors can be used to study proteins in real time or can
      be incorporated into inexpensive portable devices for the detection of analytes
      with high selectivity. 

PMID- 25871547
TI  - High-Throughput HIV-Cell Fusion Assay for Discovery of Virus Entry Inhibitors.
AB  - HIV-1 initiates infection by merging its envelope membrane with the target cell
      membrane, a process that is mediated by the viral Env glycoprotein following its
      sequential binding to CD4 and coreceptors, CXCR4 or CCR5. Although HIV-1 fusion
      has been a target for antiviral therapy, the virus has developed resistance to
      drugs blocking the CCR5 binding or Env refolding steps of this process. This
      highlights the need for novel inhibitors. Here, we adapted and optimized an
      enzymatic HIV-cell fusion assay, which reports the transfer of virus-encapsulated
      beta-lactamase into the cytoplasm, to high-throughput screening (HTS) with a 384
      well format. The assay was robustly performed in HTS format and was validated by
      the pilot screen of a small library of pharmacologically active compounds.
      Several hits identified by screening included a prominent cluster of purinergic
      receptor antagonists. Functional studies demonstrated that P2X1 receptor
      antagonists selectively inhibited HIV-1 fusion without affecting the fusion
      activity of an unrelated virus that enters cells through an endocytic route. The
      inhibition of HIV-cell fusion by P2X1 antagonists was not through downmodulation
      of the cell surface expression of CD4 or coreceptors, thus implicating P2X1
      receptor in the HIV-1 fusion step. The ability of these antagonists to inhibit
      viruses regardless of their coreceptor (CXCR4 or CCR5) preference indicates that
      fusion is blocked at a late step downstream of coreceptor binding. A future large
      scale screening campaign for HIV-1 fusion inhibitors, using the above functional
      readout, will likely reveal novel classes of inhibitors and suggest potential
      targets for antiviral therapy. 

PMID- 25871549
TI  - The responsiveness of the International Prostate Symptom Score, Incontinence
      Impact Questionnaire-7 and Depression, Anxiety and Stress Scale-21 in patients
      with lower urinary tract symptoms.
AB  - AIMS: To examine the responsiveness of a combined symptom severity and health
      related quality of life measure, condition-specific health-related quality of
      life measure and mental health measure in patients with lower urinary tract
      symptoms. BACKGROUND: To establish the responsiveness of measures that accurately
      capture the change in health status of patients is crucial before any
      longitudinal studies can be appropriately planned and evaluated. DESIGN:
      Prospective longitudinal observational study. METHODS: 402 patients were surveyed
      at baseline and 1-year using the International Prostate Symptom Score, the
      Incontinence Impact Questionnaire-7 and Depression, Anxiety and Stress Scales-21.
      The internal and external responsiveness were assessed. Surveys were conducted
      from March 2013-July 2014. RESULTS: In participants with improvements, the
      internal responsiveness for detecting positive changes was satisfactory in males
      and females for all scales, expect for the Depression subscale. The health
      related quality of life question of the International Prostate Symptom Score was
      more externally responsive than the Incontinence Impact Questionnaire-7.
      CONCLUSIONS: The International Prostate Symptom Score and Anxiety and Stress
      subscales were more responsive in males than in females. The symptom questions of
      the International Prostate Symptom Score and Anxiety and Stress subscales were
      not externally responsive in females. The health-related quality of life question
      of the International Prostate Symptom Score outperformed the Incontinence Impact
      Questionnaire-7 in both males and females, in terms of external responsiveness.

PMID- 25871550
TI  - CrossTalk proposal: bradycardia in the trained athlete is attributable to high
      vagal tone.

PMID- 25871551
TI  - CrossTalk opposing view: bradycardia in the trained athlete is attributable to a
      downregulation of a pacemaker channel in the sinus node.

PMID- 25871552
TI  - Rebuttal from John H. Coote and Michael J. White.

PMID- 25871553
TI  - Rebuttal from Alicia D'Souza, Sanjay Sharma and Mark R. Boyett.

PMID- 25871554
TI  - A novel fat connection from gut to brain.

PMID- 25871555
TI  - Pannexins: the 'nexus' between urothelium ATP production and extracellular
      release.

PMID- 25871556
TI  - Breathing in exercise: battle of the sexes.

PMID- 25871557
TI  - Platelet-derived growth factor receptor-alpha-positive cells: new players in
      nerve-mediated purinergic responses in the colon.

PMID- 25871558
TI  - Preserving muscle health and wellbeing for long-term cancer survivors.

PMID- 25871559
TI  - Clarity for 5'-AMP-activated protein kinase--dissecting out human skeletal muscle
      responses to exercise.

PMID- 25871560
TI  - Rac1: an emerging player in stretch-stimulated glucose transport.

PMID- 25871561
TI  - Transcriptome and proteome dynamics in the cardiovascular system.

PMID- 25871563
TI  - Recent advances in carbon nanospheres: synthetic routes and applications.
AB  - Carbon-based materials are the most popular material types in both fundamental
      research and industrial applications, partly because of their well-controlled
      nano-morphologies. In the past two decades, we have witnessed a number of
      breakthroughs in carbon research: fullerenes, carbon nanotubes, and more recently
      graphene. Nowadays, carbon nanospheres are attracting more and more attention
      worldwide due to their excellent performance in various fields: drug delivery,
      heterogeneous catalysis, encapsulation of support and electrode materials.
      Actually, spherical carbon is an old material, whereas controlling carbon spheres
      in the nanometer range is a recent story. In the past 5 years, it has become
      possible to precisely control the particle size, surface area, pore size,
      chemical composition, and dispersity of carbon nanospheres. Toward this end, a
      number of synthetic strategies are emerging, such as hydrothermal carbonization
      of biomass-based resources, extended Stober synthesis, and organic-organic self
      assembly via different binding methods. In this feature article, we summarize
      recent routes for carbon nanospheres and briefly touch on their applications to
      shed light on the potential of this field. Throughout this article, a special
      emphasis is placed on the possible modulation of spherical structures at the
      nanoscale, and we wish to inspire many more designs and applications of carbon
      nanostructures in the near future. 

PMID- 25871562
TI  - Prevention of statin-induced myopathy--do not stop physical activity.

PMID- 25871564
TI  - Clinical effectiveness and economic costs of group versus one-to-one education
      for short-chain fermentable carbohydrate restriction (low FODMAP diet) in the
      management of irritable bowel syndrome.
AB  - BACKGROUND: Restriction of fermentable oligosaccharides, disaccharides,
      monosaccharides and polyols (FODMAPs) is an effective dietary treatment for
      irritable bowel syndrome (IBS). Patient dietary education is essential but labour
      intensive. Group FODMAP education may alleviate this somewhat but has not
      previously been investigated. The present study aimed to investigate the clinical
      effectiveness of low FODMAP group education in patients with IBS and to explore
      the cost of a group pathway. METHODS: Patients with IBS (n = 364) were assessed
      for their suitability to attend dietitian-led group education or traditional one
      to-one education in a novel group pathway. Clinical effectiveness (global symptom
      question, symptom prevalence, stool output) were compared at baseline and follow
      up using the chi-squared test. The costs of the novel group pathway were assessed
      using a decision model. RESULTS: The global symptom question indicated more
      patients were satisfied with their symptoms following dietary advice, in both
      group education [baseline 48/263 (18%) versus follow-up 142/263 (54%), P < 0.001]
      and one-to-one education [baseline 5/101 (5%) versus follow-up 61/101 (60%), P <
      0.001], with no difference between group and one-to-one education at follow-up (P
      = 0.271). Overall, there was a significant decrease in symptom severity from
      baseline to follow-up (P < 0.001 for both groups) but no difference in symptom
      response between group and one-to-one education. The cost for the group education
      pathway for all 364 patients was L31 713.36. CONCLUSIONS: The present study shows
      that dietitian-led FODMAP group education is clinically effective and the costs
      associated with a FODMAP group pathway are worthy of further consideration for
      routine clinical care.

PMID- 25871565
TI  - FAMILIARITY TRANSFER AS AN EXPLANATION OF THE DEJA VU EFFECT.
AB  - Deja vu is often explained in terms of an unconscious transfer of familiarity
      between a familiar object or objects and accompanying new objects. However,
      empirical research tests more the priming effectiveness than such a transfer.
      This paper reviews the main explanations of deja vu, proposes a cognitive model
      of the phenomenon, and tests its six major assumptions. The model states that a
      sense of familiarity can be felt toward an objectively new stimulus (point 1) and
      that it can be transferred from a known stimulus to a novel one (point 2) in a
      situation where the person is unaware of such a transfer (point 3). The criteria
      for deja vu are that the known and the novel stimuli may have graphical or
      semantic similarity, but differences exclude priming explanations (point 4); the
      familiarity measure should be of an non-rational nature (sense of familiarity
      rather than recognition; point 5); and that the feeling of familiarity toward a
      novel stimuli produces a conflict, which could be measured by means of increased
      reaction (point 6). 119 participants were tested in three experiments. The
      participants were to assess the novel stimuli in terms of their sense of
      familiarity. The novel stimuli were primed or were not primed by the known
      stimulus (Exp. 1) or primed by the known vs a novel stimulus (Exp. 2 and 3). The
      priming was subliminal in all the experiments. Reaction times were measured in
      Exps. 2 and 3. The participants assessed the novel stimuli as more familiar when
      they were preceded by a known stimulus than when they were not (Exp. 1) or when
      they were preceded by a novel stimulus (Exps. 2 and 3). Reaction times were
      longer for assessments preceded by known stimulus than for assessments preceded
      by a novel stimulus, which contradicts the priming explanations. The results seem
      to support all six points of the proposed model of the mechanisms underlying the
      deja vu experience.

PMID- 25871567
TI  - FACTOR ANALYSES OF THE McGILL PAIN QUESTIONNAIRE (MPQ) IN ACUTE AND CHRONIC PAIN
      PATIENTS.
AB  - The McGill Pain Questionnaire (MPQ) aims to measure sensory, affective, and
      evaluative dimensions of pain. However, the structural dimensionality of the MPQ
      remains somewhat uncertain. Exploratory (EFA) factor analyses were used to
      investigate the structure of the MPQ based on the responses of a diverse sample
      of 448 pain patients (M age = 43.1 yr., SD = 19.3). The EFA employed a
      methodologically sound iterative maximum-likelihood procedure, together with
      direct oblimin oblique simple structure rotation. Perusal of the 3-, 4-, and 5
      factor solutions suggested that the MPQ measures two separate sensory dimensions
      of pain, while affective and evaluative dimensions were not sharply delineated,
      suggesting that the MPQ structure requires some revision.

PMID- 25871566
TI  - WIDE RANGE ACHIEVEMENT TEST IN AUTISM SPECTRUM DISORDER: TEST-RETEST STABILITY.
AB  - The principal goal of this descriptive study was to establish the test-retest
      stability of the Reading, Spelling, and Arithmetic subtest scores of the Wide
      Range Achievement Test (WRAT-3) across two administrations in individuals with
      autism spectrum disorder. Participants (N = 31) were males ages 6-22 years (M =
      15.2, SD = 4.0) who were part of a larger ongoing longitudinal study of brain
      development in children and adults with autism spectrum disorder (N = 185). Test
      retest stability for all three subtests remained consistent across administration
      periods (M = 31.8 mo., SD = 4.1). Age at time of administration, time between
      administrations, and test form did not significantly influence test-retest
      stability. Results indicated that for research involving individuals with autism
      spectrum disorder with a full scale intelligence quotient above 75, the WRAT-3
      Spelling and Arithmetic subtests have acceptable test-retest stability over time
      and the Reading subtest has moderate test-retest stability over time.

PMID- 25871568
TI  - EXAMINING THE DIMENSIONALITY OF COLQUITT'S ORGANIZATIONAL JUSTICE SCALE IN A
      PUBLIC HEALTH SECTOR CONTEXT.
AB  - In 2001, Colquitt developed an Organizational Justice Scale that intended to
      measure procedural, distributive, interpersonal, and informational justice. The
      dimensionality of the scale has been tested in subsequent studies with diverging
      results. Given the fact that contextual differences may account for more
      variation across research sites than individual differences, the deviating
      research findings may be due to context. This study examined the dimensionality
      of Colquitt's Organizational Justice Scale in a new context: the public health
      sector. The procedural and informational justice dimensions were highly
      correlated, but confirmatory factor analysis showed that a four-factor solution
      provided a better fit than a three-factor solution. All fit indices for the four
      factor model were consistent with a good model. There was, however, evidence of a
      potential omitted factor, procedural-voice justice, which has also been found in
      a previous examination of the measure in the public sector.

PMID- 25871569
TI  - Platelet to lymphocyte ratio as a new prognostic for patients with metastatic
      renal cell cancer.
AB  - AIM: The objective of this study was to evaluate the blood platelet-lymphocyte
      ratio (PLR) for its prognostic value in patients with metastatic renal cell
      cancer (RCC). METHODS: We retrospectively reviewed 100 patients diagnosed with
      metastatic RCC previously treated with tyrosine kinase inhibitors from three
      centers. We assessed the prognostic value of pretreatment PLR and other clinical
      and laboratory parameters based on univariate and multivariate analyses. RESULTS:
      Median progression-free survival (PFS) was 7.3 months and median overall survival
      (OS) was 15.3 months. Multivariate analysis revealed that PFS is significantly
      affected by ECOG PS (P = 0.047), PLR (P = 0.029) and calcium level (P = 0.023).
      Median PFS was 13.9 versus 5.3 months in patients with PLR <= 210 versus PLR >
      210 (log rank; P = 0.001). Median OS was 25.9 versus 10.9 months with PLR <= 210
      versus PLR > 210 (log rank; P = 0.013). CONCLUSIONS: This study shows that
      increased pretreatment PLR is an independent prognostic indicator in patients
      with metastatic RCC who use tyrosine kinase inhibitors.

PMID- 25871570
TI  - Plasma thrombospondin 1 as a predictor of postoperative liver dysfunction.
AB  - BACKGROUND: Liver regeneration following liver resection involves a complex
      interplay of growth factors and their antagonists. Thrombospondin 1 has recently
      been identified as a critical inhibitor of liver regeneration by the activation
      of transforming growth factor beta1 in mice, and preliminary data seem to confirm
      its relevance in humans. This study aimed to confirm these observations in an
      independent validation cohort. METHODS: Perioperative circulating levels of
      thrombospondin 1 were measured in patients undergoing liver resection between
      January 2012 and September 2013. Postoperative liver dysfunction was defined
      according to the International Study Group of Liver Surgery and classification of
      morbidity was based on the criteria by Dindo et al. RESULTS: In 85 patients (44
      major and 41 minor liver resections), plasma levels of thrombospondin 1 increased
      1 day after liver resection (mean 51.6 ng/ml before surgery and 68.3 ng/ml on
      postoperative day 1; P = 0.001). Circulating thrombospondin 1 concentration on
      the first postoperative day specifically predicted liver dysfunction (area under
      the receiver operating characteristic (ROC) curve 0.818, P = 0.003) and was
      confirmed as a significant predictor in multivariable analysis (Exp(B) 1.020, 95
      per cent c.i. 1.005 to 1.035; P = 0.009). Patients with a high thrombospondin 1
      concentration (over 80 ng/ml) on postoperative day 1 more frequently had
      postoperative liver dysfunction than those with a lower level (28 versus 2 per
      cent) and severe morbidity (44 versus 15 per cent), and their length of hospital
      stay was more than doubled (19.7 versus 9.9 days). CONCLUSION: Thrombospondin 1
      may prove a helpful clinical marker to predict postoperative liver dysfunction as
      early as postoperative day 1.

PMID- 25871571
TI  - Systematic review with meta-analysis: post-infectious irritable bowel syndrome
      after travellers' diarrhoea.
AB  - BACKGROUND: Gastrointestinal infection is known as a risk factor for the
      development of the irritable bowel syndrome (post-infectious irritable bowel
      syndrome, PI-IBS). The incidence of PI-IBS ranges between 3% and over 30% of
      people after infectious gastroenteritis. AIM: To perform a meta-analysis pools
      and report data concerning the relative risk (RR) of PI-IBS after TD. METHODS:
      Database search using Medline through PubMed, Scopus, EBM Reviews (Cochrane
      Database of Systematic Reviews) and PsycINFO was performed to identify relevant
      studies. Those that met the inclusion criteria were pooled. A random effects
      model (Mantel-Haenszel) was performed. RESULTS: Six eligible studies were found.
      In three of six studies, the authors reported a statistically significant
      association of TD and PI-IBS. The pooled RR was 3.35 (95% CI: 2.22-5.05) with a
      significant overall effect (P < 0.00001). Overall PI-IBS incidence was 5.4% in TD
      subjects and 1.4% in healthy subjects. There was no significant heterogeneity
      within the pooled studies (I(2)  = 5%). Self-reported TD alone resulted in an
      over 1.5-fold RR for PI-IBS compared to laboratory-confirmed TD [RR 3.90 (95% CI:
      2.35-6.49) vs. RR 2.42 (95% CI: 1.22-4.78)]. CONCLUSIONS: There is a strong
      association between travellers' diarrhoea and post-infectious irritable bowel
      syndrome. Self-reports of exposure seem to result in a higher post-infectious
      irritable bowel syndrome occurrence than laboratory-confirmed cases of
      travellers' diarrhoea, but further studies are needed to confirm this finding.
      Finally, potential influences of the selection of an appropriate study population
      on post-infectious irritable bowel syndrome epidemiology are discussed.

PMID- 25871572
TI  - Asynchronous Crystal Cell Expansion during Lithiation of K(+)-Stabilized alpha
      MnO2.
AB  - alpha-MnO2 is a promising material for Li-ion batteries and has unique tunneled
      structure that facilitates the diffusion of Li(+). The overall electrochemical
      performance of alpha-MnO2 is determined by the tunneled structure stability
      during its interaction with Li(+), the mechanism of which is, however, poorly
      understood. In this paper, a novel tetragonal-orthorhombic-tetragonal symmetric
      transition during lithiation of K(+)-stabilized alpha-MnO2 is observed using in
      situ transmission electron microscopy. Atomic resolution imaging indicated that 1
      * 1 and 2 * 2 tunnels exist along c ([001]) direction of the nanowire. The
      morphology of a partially lithiated nanowire observed in the ?100? projection is
      largely dependent on crystallographic orientation ([100] or [010]), indicating
      the existence of asynchronous expansion of alpha-MnO2's tetragonal unit cell
      along a and b lattice directions, which results in a tetragonal-orthorhombic
      tetragonal (TOT) symmetric transition upon lithiation. Such a TOT transition is
      confirmed by diffraction analysis and Mn valence quantification. Density
      functional theory (DFT) confirms that Wyckoff 8h sites inside 2 * 2 tunnels are
      the preferred sites for Li(+) occupancy. The sequential Li(+) filling at 8h sites
      leads to asynchronous expansion and symmetry degradation of the host lattice as
      well as tunnel instability upon lithiation. These findings provide fundamental
      understanding for appearance of stepwise potential variation during the discharge
      of Li/alpha-MnO2 batteries as well as the origin for low practical capacity and
      fast capacity fading of alpha-MnO2 as an intercalated electrode. 

PMID- 25871573
TI  - Influence of -141C Ins/Del Polymorphism in DRD2 Gene on Clinical Symptoms and
      Plasma Homovanillic Acid Levels in the Treatment of Schizophrenia With
      Aripiprazole.

PMID- 25871574
TI  - A critical interaction between ertapenem and valproic acid.

PMID- 25871575
TI  - Worry dissected.

PMID- 25871576
TI  - Multitask Imaging Monitor for Surgical Navigation: Combination of Touchless
      Interface and Head-Mounted Display.
AB  - As a result of the dramatic improvements in the resolution, wearability, and
      weight of head-mounted displays (HMDs), they have become increasingly applied in
      the medical field as personal imaging monitors. The combined use of a multiplexer
      with an HMD allows the wearer to simultaneously and seamlessly monitor multiple
      streams of imaging information through the HMD. We developed a multitask imaging
      monitor for surgical navigation by combining a touchless surgical imaging control
      system with an HMD. This system is composed of a standard color digital video
      camera mounted on the HMD and computer software that enables the identification
      of the number of pictured fingertips from the video camera image. The HMD wearer
      uses this information as a touchless interface for the operating multiplexer,
      which can control the arrays and types of imaging information displayed on the
      HMD. We used this system in an experimental demonstration during a single-port
      gasless partial nephrectomy. The use of this multitask imaging monitor using a
      touchless interface would refine the surgical workflow, especially during
      surgical navigation.

PMID- 25871577
TI  - Synthesis of Functionalized Alkylidene Indanes and Indanones through Tandem
      Phosphine-Palladium Catalysis.
AB  - Densely functionalized alkylidene indanes and indanones can be prepared
      efficiently in one pot, in high yields with good stereoselectivities (in some
      cases exclusively the Z-isomer), through a route involving phosphine-catalyzed
      Michael addition followed by palladium-catalyzed Heck cyclization. These
      transformations tolerate substrates bearing various substituents around the
      indane/indanone motif. Employing this technology, a concise formal synthesis of
      sulindac, a nonsteroidal anti-inflammatory drug, has been established. 

PMID- 25871578
TI  - Pancreatic Atrophy in Hepatocellular Carcinoma Patients Receiving Long-Term
      Treatment with Sorafenib.
AB  - OBJECTIVE: To date, sorafenib is the only approved systemic therapy for advanced
      hepatocellular carcinoma (HCC). Pancreatic atrophy has recently been reported in
      2 patients as a novel side effect after long-term sorafenib treatment. METHODS:
      We retrospectively analyzed clinical and radiological data of patients with
      advanced HCC with long-term treatment of sorafenib (median 279 days, range 153
      826 days). Pancreata were semi-manually segmented section by section to calculate
      the pancreas volumes before and under sorafenib treatment. RESULTS: Sorafenib
      reduced pancreatic volume in 18/19 (95%) HCC patients with a mean pancreatic
      volume loss of 25% (p = 0.002). Pancreatic volume loss depended on the dose (r =
      0.36) and exposure time of sorafenib (r = 0.35) and was detectable as early as
      after 3 months of sorafenib treatment and already after a cumulative sorafenib
      dose of <100 g. Median overall survival was 13.2 months (range 7.8-31.3 months)
      but did not correlate with sorafenib-induced pancreatic volume reduction (hazard
      ratio 1.002, 95% confidence interval 0.981-1.060, p = 0.24). CONCLUSION: We could
      confirm pancreatic atrophy as a novel adverse event of sorafenib therapy in HCC
      patients, correlating with sorafenib dose and exposure time.

PMID- 25871579
TI  - Doubly chloro bridged dimeric copper(II) complex: magneto-structural correlation
      and anticancer activity.
AB  - We have synthesized and structurally characterized a new doubly chloro bridged
      dimeric copper(II) complex, [Cu2(MU-Cl)2(HL)2Cl2] (1) based on a Schiff base
      ligand, 5-[(pyridin-2-ylmethylene)-amino]-pentan-1-ol). Single crystal X-ray
      diffraction shows the presence of dinuclear copper(II) centres in a square
      pyramidal geometry linked by obtuse double chloro bridge. The magnetic study
      illustrated that weak antiferromagnetic interactions (J = -0.47 cm(-1)) prevail
      in complex 1 which is well supported by magneto-structural correlation. This
      compound adds to the library of doubly chloro bridged copper(ii) complexes in the
      regime of spin state cross over. DFT calculations have been conducted within a
      broken-symmetry (BS) framework to investigate the exchange interaction further
      which depicts that the approximate spin projection technique yields the best
      corroboration of the experimental J value. Spin density plots show the presence
      of an ~0.52e charge residing on the copper atom along with a substantial charge
      on bridging and peripheral chlorine atoms. The potential of complex1 to act as an
      anticancer agent is thoroughly examined on a series of liver cancer cell lines
      and screening shows the HepG2 cell line exhibits maximum cytotoxicity by
      phosphatidyl serine exposure in the outer cell membrane associated with ROS
      generation and mitochondrial depolarization with increasing time in the in vitro
      model system.

PMID- 25871580
TI  - Regulatory guidance gaps associated with clinical sample bioanalysis.

PMID- 25871581
TI  - What role can metabolomics play in the discovery and development of new medicines
      for infectious diseases?

PMID- 25871582
TI  - Paper-based microfluidic devices in bioanalysis: how far have we come?

PMID- 25871583
TI  - The versatility in LC selectivity attainable with the silica base and associated
      bonded phases.

PMID- 25871584
TI  - Identification of a novel human circulating metabolite of tenofovir disoproxil
      fumarate with LC-MS/MS.
AB  - BACKGROUND: Tenofovir disoproxil fumarate (TDF) is an antiretroviral drug used
      for the treatment of Human Immunodeficiency Virus and Hepatitis B infections.
      RESULTS: A metabolite that has previously not been observed in the circulation of
      humans was detected by LC-MS/MS in early time point plasma samples following
      administration of TDF to healthy volunteers. The metabolite was identified using
      a range of LC-MS/MS-based techniques as a monoester of TDF, derived from the
      partially hydrolyzed bis-ester prodrug. TDF, when spiked into plasma, was
      observed to degrade first to the putative monoester and subsequently to
      tenofovir. CONCLUSION: The presence of this unstable metabolite in some samples
      has implications for sample collection, handling and storage in studies of
      tenofovir where serum concentrations are determined.

PMID- 25871585
TI  - Development of supported liquid-phase microextraction probes for in vivo PK
      studies.
AB  - BACKGROUND: A new sample preparation method termed supported liquid-phase
      microextraction is proposed. With this technique, the extraction phase is a
      liquid immobilized inside the pores of a membrane coated on a solid support.
      METHODOLOGY: Supported liquid-phase microextraction probes were prepared by
      coating wires with porous polyacrylonitrile followed by saturation with 1
      octanol. The probes were introduced inside hypodermic needles and used for in
      vivo extraction of oxybutynin from the blood and tissues of rabbits. The linear
      range of the method was from 0.5 to 500 ng/ml. CONCLUSION: The proposed method
      was successfully applied to monitor the PK profile of oxybutynin. The drug
      followed a two-compartment model, with a volume of distribution of 14 l/kg and a
      half-life of 76 min.

PMID- 25871586
TI  - Urinary metabolomics and biomarkers of aristolochic acid nephrotoxicity by UPLC
      QTOF/HDMS.
AB  - BACKGROUND: Drug-induced nephrotoxicity was one of the most important health
      problems, with increasing morbidity and mortality. Urinary metabolomics based on
      ultra performance liquid chromatography coupled with quadrupole time-of-flight
      high-definition mass spectrometry was applied to aristolochic acid (AA)
      nephrotoxicity rats to characterize the excretion pathways of endogenous
      metabolites. RESULTS: Compared with the control rats, serum creatinine, serum
      blood urea nitrogen and urine protein levels were significantly increased in AA
      nephrotoxicity rats. Metabolomics showed that metabolites including citrate,
      aconitate, fumarate, glucose, creatinine, p-cresyl sulfate, indoxyl sulfate,
      hippuric acid, phenylacetylglycine, kynurenic acid, indole-3-carboxylic acid,
      spermine, uric acid, allantoin, cholic acid and taurine were identified in AA
      nephrotoxicity rats. CONCLUSION: The identified metabolites suggested that AA
      nephrotoxicity rats occurred perturbations in Krebs cycle, gut microflora
      metabolism, amino acid metabolism, purine metabolism and bile acid biosynthesis.

PMID- 25871587
TI  - HPLC-MS/MS method for the determination of four lignans from Phyllanthus urinaria
      L. in rat plasma and its application.
AB  - BACKGROUND: Phyllanthus urinaria L. showed significant hepatoprotective and anti
      HBV activities. A sensitive and rapid HPLC-MS/MS method has been developed and
      validated for the simultaneous determination of hypophyllanthin, phyllanthin,
      nirtetralin and niranthin from Phyllanthus urinaria L. in rat plasma. The
      analytes were extracted from rat plasma with n-hexane/isopropanol and diazepam
      was used as the internal standard. RESULTS: The calibration curves were linear (r
      > 0.9971) over a concentration range of 2-1000 ng/ml for hypophyllanthin and
      nirtetralin, and 1-1000 ng/ml for phyllanthin and niranthin. The precision,
      accuracy, recovery and stability were deemed acceptable. CONCLUSION: The HPLC
      MS/MS method was successfully applied to a PK study of the four lignans in rats
      after oral administration of Phyllanthus urinaria L. extract.

PMID- 25871588
TI  - Determination of alpha-ketoglutaric and pyruvic acids in urine as potential
      biomarkers for diabetic II and liver cancer.
AB  - BACKGROUND: A simple and sensitive hollow fiber-liquid phase microextraction with
      in situ derivatization method was developed for the determination of alpha
      ketoglutaric (alpha-KG) and pyruvic acids (PA) in small-volume urine samples.
      2,4,6-trichloro phenyl hydrazine was used as derivatization agent. RESULTS: Under
      the optimum extraction conditions, enrichment factors of 742 and 400 for alpha-KG
      and PA, respectively, were achieved. Calibration curves were linear over the
      range 1 to 1000 ng/ml (r(2) >= 0.998). Detection and quantitation limits were
      0.03 and 0.02, and 0.10 and 0.05 ng/ml for alpha-KG and PA, respectively.
      CONCLUSION: The concentrations in diabetic II and liver cancer samples were
      significantly lower than those from healthy people, showing their potential as
      biomarkers for these diseases.

PMID- 25871589
TI  - Graphene-based protein biomarker detection.
AB  - An ability to detect and quantify protein molecules, harbingers of specific
      pathologies, potentially underpins both early disease diagnosis and an assessment
      of treatment efficacy. However, the specific detection of a particular protein
      biomarker in a complex environment is by no means an easy task and requires a
      progressive improvement in sensor technology. The high surface area, volume,
      electrical conductance, atomic level thickness and apparent biocompatibility of
      graphene makes it potentially an exceedingly powerful transducer of
      biorecognition events; the demands of its application in biosensing, and progress
      to date are reviewed herein. 

PMID- 25871590
TI  - Quantitative analysis of drugs in biological matrices by HPLC hyphenated to
      fluorescence detection.
AB  - An overview of the state-of-the art in HPLC coupled with fluorescence detection
      is presented. Over the last 20 years, the increasing number of methodological
      papers on this topic (4082 between 1994 and 2004 and 7725 between 2004 and 2014)
      is testament to its utility in bioanalytical applications. Compared with
      conventional UV absorbance detection used in HPLC, fluorescence detection can
      greatly enhance the sensitivity leading to limits of detection similar to those
      obtained with mass spectrometry, offering researchers a sensitive, robust and
      relatively inexpensive instrumental method. This work will focus on the analysis
      of pharmaceutical compounds in different biological matrices, either naturally
      fluorescent or derivatized with a fluorescent agent, and some of them chiral.
      Therapeutic applications, sample preparation and derivatization, sensitivity for
      each example are described. 

PMID- 25871591
TI  - Antibody-free workflows for protein quantification by LC-MS/MS.
AB  - Antibody-free approaches for quantitative LC-MS/MS-based protein bioanalysis are
      reviewed and critically evaluated, and compared with the more widely used
      immunoaffinity-based approaches. Antibody-free workflows will be divided into
      four groups and discussed in the following order: direct analysis of signature
      peptides after proteolytic digestion; enrichment of target proteins and signature
      peptides by fractionated protein precipitation; enrichment of target proteins and
      signature peptides by reversed-phase and ion-exchange solid-phase extraction; and
      enrichment of target proteins and signature peptides by (antibody-free) affinity
      solid-phase extraction. 

PMID- 25871592
TI  - Observational characterization of sensory interests, repetitions, and seeking
      behaviors.
AB  - Sensory interests, repetitions, and seeking behaviors (SIRS) are common among
      children with autism spectrum disorder (ASD) and other developmental disabilities
      (DD) and involve unusual actions that intensify or reinforce a sensory
      experience. Researchers and practitioners typically use parent-report measures or
      informal clinical observations to understand the presence and nature of SIRS. In
      this study, we used a scoring supplement to the Sensory Processing Assessment for
      Young Children, an observational measure, to characterize SIRS across three
      groups of children-those with ASD (n=40), DD (n=37), and typical development
      (n=39). Group differences were identified in frequency and intensity of overall
      SIRS, complexity of SIRS, and incidence of particular types of SIRS (i.e.,
      posturing, sighting, proprioceptive seeking, spinning). Facial affect was also
      explored and found to be primarily neutral during engagement in SIRS across
      groups. Implications for practice and future research are discussed.

PMID- 25871594
TI  - Handwriting Proficiency Screening Questionnaire for Children (HPSQ-C):
      Development, Reliability, and Validity.
AB  - OBJECTIVE: To adapt the Handwriting Proficiency Screening Questionnaire (HPSQ),
      previously designated for adults, into a children's self-report version (the HPSQ
      for Children, or HPSQ-C) and to examine its reliability and validity. METHOD:
      Participants included 230 children ages 7-14 yr from regular schools in Israel.
      The questionnaire's content validity, internal consistency, and concurrent and
      construct validity were assessed. RESULTS: The tool demonstrated good internal
      consistency (alpha=.77). We found a significant moderate correlation between
      final HPSQ-C scores and the HPSQ, r=.51, p<.001, establishing the HPSQ-C's
      concurrent validity. Construct validity was also confirmed. Results demonstrated
      that the HPSQ-C significantly distinguished between children with and without
      handwriting deficiencies on the basis of measures of handwriting product (Hebrew
      Handwriting Evaluation) and handwriting process (Computerized Penmanship
      Evaluation Tool). CONCLUSION: The HPSQ-C is suitable for identification of
      handwriting deficiency among school-aged children and is appropriate for varied
      academic and clinical uses.

PMID- 25871593
TI  - Feasibility of a sensory-adapted dental environment for children with autism.
AB  - OBJECTIVE: To provide an example of an occupational therapy feasibility study and
      evaluate the implementation of a randomized controlled pilot and feasibility
      trial examining the impact of a sensory-adapted dental environment (SADE) to
      enhance oral care for children with autism spectrum disorder (ASD). METHOD:
      Twenty-two children with ASD and 22 typically developing children, ages 6-12 yr,
      attended a dental clinic in an urban hospital. Participants completed two dental
      cleanings, 3-4 mo apart, one in a regular environment and one in a SADE.
      Feasibility outcome measures were recruitment, retention, accrual, dropout, and
      protocol adherence. Intervention outcome measures were physiological stress,
      behavioral distress, pain, and cost. RESULTS: We successfully recruited and
      retained participants. Parents expressed satisfaction with research study
      participation. Dentists stated that the intervention could be incorporated in
      normal practice. Intervention outcome measures favored the SADE condition.
      CONCLUSION: Preliminary positive benefit of SADE in children with ASD warrants
      moving forward with a large-scale clinical trial.

PMID- 25871596
TI  - Parents' understanding of play for children with cerebral palsy.
AB  - OBJECTIVE: To present the findings of an exploratory study regarding the
      experience of play as an everyday occupation for children with severe cerebral
      palsy from their parents' perspective. METHOD: We took a qualitative methodology
      and interpretive descriptive approach. After ethical approval, 7 participants
      were recruited and completed an interview and contextual information sheet.
      RESULTS: The interview data led to the exploration of four themes: typical play,
      burden of play, expanding the concept of play, and therapy and play. These
      components were interlinked and contributed to parents' understanding of play.
      CONCLUSION: Occupational therapy practitioners can aim to further understand the
      importance of affirming typical play, recognizing the burden of play, explaining
      expanded play, and explaining the importance of play for play's sake.

PMID- 25871595
TI  - Effectiveness of a cognitive-functional group intervention among preschoolers
      with attention deficit hyperactivity disorder: a pilot study.
AB  - OBJECTIVE: To test functional improvement after a group cognitive-functional
      occupational therapy intervention for preschoolers with attention deficit
      hyperactivity disorder (ADHD). METHOD: Seventeen preschooler-parent dyads
      attended 11 weekly group sessions focused on acquiring executive strategies
      through occupational performance. Functional improvement was measured using the
      Canadian Occupational Performance Measure (COPM) and Goal Attainment Scaling
      (GAS); executive function, using the Behavior Rating Inventory of Executive
      Function-Pediatric; ADHD symptomatology, using Conners' Parent Rating Scale
      Revised and Conners' Teacher Rating Scale-Revised; and social functioning, using
      the Social Participation scale of the Sensory Processing Measure. RESULTS:
      Significant improvement was found on the COPM and GAS measures, whereas mixed
      results were found on the other measures, with improvements found in children
      whose scores indicated impairment at baseline. CONCLUSIONS: Cognitive-functional
      group intervention appears to significantly improve daily functioning, executive
      function, and social functioning for children who demonstrate clinical
      impairment. Further research with a larger sample, a control group, and follow-up
      is required.

PMID- 25871597
TI  - Development and Evaluation of the Lifestyle History Questionnaire (LHQ) for
      People Entering Treatment for Substance Addictions.
AB  - OBJECTIVE: We developed and investigated the psychometric properties of the
      Lifestyle History Questionnaire (LHQ), a self-report instrument designed to
      measure the extent of occupational dysfunction attributable to substance abuse.
      METHOD: The instrument was developed using concepts in the ecological models of
      occupational therapy and in the work of William L. White, who defined addiction
      culture in terms of the patterns of life in context. We analyzed data from two
      field tests using both classical test theory and item response theory. RESULTS:
      The final version of the instrument has 70 items, 1 unifying construct, and 8
      subscales. We found it to be valid and reliable (alpha=.93) for measuring the
      extent of occupational dysfunction and specific areas of strengths and
      weaknesses. CONCLUSION: The LHQ is a promising new instrument, the first of its
      kind to measure occupational dysfunction in context for people with substance
      addictions.

PMID- 25871598
TI  - Dual-task performance involving hand dexterity and cognitive tasks and daily
      functioning in people with schizophrenia: a pilot study.
AB  - OBJECTIVE: This study investigated separate and concurrent performance on
      cognitive and hand dexterity tasks and the relationship to daily functioning in
      16 people with schizophrenia and 16 healthy control participants. METHOD:
      Participants performed the Purdue Pegboard Test and the Serial Seven Subtraction
      Test under single- and dual-task conditions and completed two daily functioning
      evaluations. RESULTS: The hand dexterity of all participants declined in the dual
      task condition, but the discrepancy between single-task and dual-task hand
      dexterity was greater in the schizophrenia group than in the control group
      (p<.03, d>.70, for all). The extent of discrepancy in hand dexterity was
      negatively correlated with daily functioning in the schizophrenia group (rs=-.3
      to -.5, ps=.04-.26). CONCLUSION: Ability to perform dual tasks may be an
      indicator of daily functioning in people with schizophrenia. Use of dual-task
      training may be considered as a therapeutic activity with these clients.

PMID- 25871599
TI  - Client and therapist perspectives on the influence of low vision and chronic
      conditions on performance and occupational therapy intervention.
AB  - OBJECTIVE: We explored how vision loss and comorbid chronic conditions influence
      occupational therapy intervention by gathering perspectives from occupational
      therapists treating clients with low vision and from older adults with low
      vision. METHOD: We surveyed 59 occupational therapists on the frequency of
      comorbidities in their clients and their influence on low vision intervention.
      Eight older adults with low vision participated in in-depth interviews and
      observations on the influence of low vision and comorbidities on their
      occupational performance. Conclusions reflect data analysis from both methods.
      RESULTS: The occupational therapists modified low vision interventions to address
      the added effect of each comorbidity. Modifications included more treatment
      sessions, home visits, referrals to other professions, and provision of
      strategies to address comorbidities. The older adults viewed vision loss as a
      stronger influence than comorbidities on independence in daily occupations.
      CONCLUSION: Both vision loss and comorbidities influence occupational
      performance, supporting the need for interventions to address both conditions.

PMID- 25871600
TI  - Instrumental activities of daily living performance and role satisfaction in
      people with and without mild cognitive impairment: a pilot project.
AB  - OBJECTIVE: We investigated differences in observed performance of instrumental
      activities of daily living (IADLs) and self-reported satisfaction with social
      role performance between people with amnestic mild cognitive impairment (a-MCI)
      and age- and gender-matched control participants. METHOD: We measured observed
      performance of 14 IADLs using the Independence, Safety, and Adequacy domains of
      the Performance Assessment of Self-Care Skills (PASS) and the Patient-Reported
      Outcomes Measurement Information Systems (PROMIS) to examine satisfaction with
      social role performance. RESULTS: Total PASS scores were significantly lower in
      participants with a-MCI (median=40.6) than in control participants (median=44.2;
      p=.006). Adequacy scores were also significantly lower. No significant
      differences were found between groups on the PROMIS measures. CONCLUSION: IADL
      differences between groups were related more to errors in adequacy than to safety
      and independence. Occupational therapy practitioners can play a key role in the
      diagnosis and treatment of subtle IADL deficits in people with MCI.

PMID- 25871601
TI  - Comparing caregiver and clinician predictions of fitness to drive in people with
      Alzheimer's disease.
AB  - This observational study investigated family caregiver and clinician ratings of
      75 drivers with Alzheimer's disease against scores on a standardized road test
      and a naturalistic driving evaluation. Clinician ratings by a physician
      specialized in dementia were significantly associated with road test error scores
      (r=.25, p=.03) but not naturalistic driving errors or global ratings of road test
      and naturalistic driving performance. Caregiver ratings were unrelated to either
      driving assessment, with two exceptions; adult child ratings of driving ability
      were correlated with road test error scores (r=.43, p=.02), and spousal ratings
      were inversely correlated with global ratings. Clinician ratings of driving
      competence were modestly correlated with road test performance, but caregiver
      ratings were more complex. Adult children may be more accurate reporters of
      driving ability than spouses, possibly because of less personal bias, but the
      reasons behind this discrepancy need further investigation.

PMID- 25871602
TI  - Goals set after completing a teleconference-delivered program for managing
      multiple sclerosis fatigue.
AB  - Setting goals can be a valuable skill to self-manage multiple sclerosis (MS)
      fatigue. A better understanding of the goals set by people with MS after
      completing a fatigue management program can assist health care professionals with
      tailoring interventions for clients. This study aimed to describe the focus of
      goals set by people with MS after a teleconference-delivered fatigue management
      program and to evaluate the extent to which participants were able to achieve
      their goals over time. In total, 485 goals were set by 81 participants. Over a
      follow-up period, 64 participants rated 284 goals regarding progress made toward
      goal achievement. Approximately 50% of the rated goals were considered achieved.
      The most common type of goal achieved was that of instrumental activities of
      daily living. Short-term goals were more likely to be achieved. This study
      highlights the need for and importance of promoting and teaching goal-setting
      skills to people with MS. 

PMID- 25871603
TI  - Measuring change in somatosensation across the lifespan.
AB  - OBJECTIVE: The study aim was to determine natural variability in somatosensation
      across age groups using brief measures. We validated measures in a community
      dwelling population as part of the National Institutes of Health (NIH) Toolbox
      for Assessment of Neurological and Behavioral Function (NIH Toolbox;
      http://www.nihtoolbox.org). METHOD: Participants included community-dwelling
      children and adults (N=367, ages 3-85 yr) across seven sites. We tested haptic
      recognition, touch detection-discrimination, and proprioception using brief
      affordable measures as required by the NIH Toolbox. RESULTS: Accuracy improved
      from young children to young adults; from young to older adults, the pattern
      reversed slightly. We found significant differences between adults and older
      adults. One proprioception test (kinesthesia; p=.003) showed gender differences
      (females more accurate). We provide expected score ranges for age groups as a
      basis for understanding age-related expectations for somatosensory perception.
      CONCLUSION: The age-related patterns of somatosensory perception from this study
      refine decision making about performance.

PMID- 25871604
TI  - Behavioral intention to use a virtual instrumental activities of daily living
      system among people with stroke.
AB  - OBJECTIVE: The purpose of this study was to investigate the behavioral intention
      to use (BIU) regarding a virtual system for practicing instrumental activities of
      daily living (IADLs) among people with stroke. METHOD: Fourteen people who had
      sustained a stroke used a virtual world-based system over four sessions to
      participate in virtual occupations of preparing meals and putting away groceries.
      To investigate intention to use the technology, participants responded to a
      questionnaire based on the Technology Acceptance Model and were interviewed about
      the experience. RESULTS: Analysis of questionnaire responses revealed favorable
      attitudes toward the technology and statistically significant correlations
      between these attitudes and positive BIU. Analysis of qualitative data revealed
      four themes to support system use: Use of the affected arm increased, the virtual
      practice was enjoyable, the technology was user-friendly, and the system
      reflected real-life activities. CONCLUSION: This study shows that participants
      reported a positive BIU for the virtual system for practicing IADLs.

PMID- 25871605
TI  - Effects of deep pressure stimulation on physiological arousal.
AB  - Deep pressure stimulation has been used in therapeutic practice because of the
      assumption that it changes physiological arousal. The purpose of this study was
      to test the effects of deep pressure stimulation, applied with a Vayu Vest
      (Therapeutic Systems), on both autonomic arousal and performance in a normative
      adult sample. A repeated-measures, repeated-baseline design was used with
      participants completing a performance test before and after deep pressure
      application. A convenience sample of 50 adults participated in the study. Results
      showed that wearing the Vayu Vest for even short periods of time reduced
      sympathetic arousal and non-stimulus-driven electrical occurrences. Concomitant
      increases in parasympathetic arousal were found. Performance improvements were
      noted after wearing the Vayu Vest, potentially because of changes in arousal. We
      conclude that deep pressure stimulation is capable of eliciting changes in
      autonomic arousal and may be a useful modality in diagnostic groups seen by
      occupational therapy practitioners. 

PMID- 25871606
TI  - Fear of falling in people with chronic stroke.
AB  - OBJECTIVE: We assessed the prevalence of fear of falling (FoF) in a sample of
      people with chronic stroke and compared multiple variables (balance, anxiety,
      depression, activity and participation, and stroke severity) in people with and
      without FoF. METHOD: This study was a secondary analysis of data collected from a
      cross-sectional study of mobility after stroke in 77 participants with chronic
      stroke (>6 mo poststroke). RESULTS: Of the 77 participants, 51 (66%) reported
      experiencing FoF. People with FoF had significantly decreased balance (p<.001)
      and activity and participation (p=.006) and significantly increased anxiety
      (p=.007). People with FoF also had significantly worse stroke severity (p=.001).
      CONCLUSION: FoF is a prevalent concern in the chronic stroke population. The
      presence of FoF was associated with a variety of negative consequences.
      Occupational therapy practitioners should address FoF to help clients manage FoF
      and possibly improve recovery.

PMID- 25871608
TI  - Research opportunities in the area of home modifications.
AB  - The American Occupational Therapy Association (AOTA) Evidence-Based Practice
      Project has developed a table summarizing the research opportunities on home
      modifications. The table provides an overview of the state of current available
      evidence on interventions within the scope of occupational therapy practice and
      is based on the systematic reviews from the AOTA's Occupational Therapy Practice
      Guidelines Series. Researchers, students, and clinicians can use this information
      in developing innovative research to answer important questions within the
      occupational therapy field. 

PMID- 25871607
TI  - Role of sonographic imaging in occupational therapy practice.
AB  - Occupational therapy practice is grounded in the delivery of occupation-centered,
      patient-driven treatments that engage clients in the process of doing to improve
      health. As emerging technologies, such as medical imaging, find their way into
      rehabilitation practice, it is imperative that occupational therapy practitioners
      assess whether and how these tools can be incorporated into treatment regimens
      that are dually responsive to the medical model of health care and to the
      profession's foundation in occupation. Most medical imaging modalities have a
      discrete place in occupation-based intervention as outcome measures or for
      patient education; however, sonographic imaging has the potential to blend
      multiple occupational therapy practice forms to document treatment outcomes,
      inform clinical reasoning, and facilitate improved functional performance when
      used as an accessory tool in direct intervention. Use of medical imaging is
      discussed as it relates to occupational foundations and the professional role
      within the context of providing efficient, effective patient-centered
      rehabilitative care. 

PMID- 25871610
TI  - Truncated cross-sectional average length of life: A measure for comparing the
      mortality history of cohorts.
AB  - Period life expectancies are commonly used to compare populations, but these
      correspond to simple juxtapositions of current mortality levels. In order to
      construct life expectancies for cohorts, a complete historical series of
      mortality rates is needed, and these are available for only a subset of developed
      countries. The truncated cross-sectional average length of life (TCAL) is a new
      measure that captures historical information about all cohorts present at a given
      moment and is not limited to countries with complete cohort mortality data. The
      value of TCAL depends on the rates used to complete the cohort series, but
      differences between TCALs of two populations remain similar irrespective of the
      data used to complete the cohort series. This result is illustrated by a
      comparison of TCALs for the US with those for Denmark, Japan, and other high
      longevity countries. Specific cohorts that account for most of the disparity in
      mortality between the populations are identified.

PMID- 25871611
TI  - Cochlear NMDA receptors as a therapeutic target of noise-induced tinnitus.
AB  - BACKGROUND: Accumulating evidence suggests that tinnitus may occur despite normal
      auditory sensitivity, probably linked to partial degeneration of the cochlear
      nerve and damage of the inner hair cell (IHC) synapse. Damage to the IHC synapses
      and deafferentation may occur even after moderate noise exposure. For both
      salicylate- and noise-induced tinnitus, aberrant N-methyl-d-aspartate (NMDA)
      receptor activation and related auditory nerve excitation have been suggested as
      origin of cochlear tinnitus. Accordingly, NMDA receptor inhibition has been
      proposed as a pharmacologic approach for treatment of synaptopathic tinnitus.
      METHODS: Round-window application of the NMDA receptor antagonist AM-101
      (Esketamine hydrochloride gel; Auris Medical AG, Basel, Switzerland) was tested
      in an animal model of tinnitus induced by acute traumatic noise. The study
      included the quantification of IHC ribbon synapses as a correlate for
      deafferentation as well as the measurement of the auditory brainstem response
      (ABR) to close-threshold sensation level stimuli as an indication of sound
      induced auditory nerve activity. RESULTS: We have shown that AM-101 reduced the
      trauma-induced loss of IHC ribbons and counteracted the decline of ABR wave I
      amplitude generated in the cochlea/auditory nerve. CONCLUSION: Local round-window
      application of AM-101 may be a promising therapeutic intervention for the
      treatment of synaptopathic tinnitus.

PMID- 25871612
TI  - Progressive Structural Brain Changes and NRG1 Gene Variants in First-Episode
      Nonaffective Psychosis.
AB  - BACKGROUND: Structural brain abnormalities are already present during the early
      phases of psychosis, but factors underlying brain volume changes are still not
      well understood. The neuregulin 1 gene (NRG1), influencing neurodevelopment and
      neuroplasticity, has been associated with schizophrenia. Our aim was to examine
      whether variations in the NRG1 gene (SNP8NRG221132, SNP8NRG6221533 and
      SNP8NRG243177 polymorphisms) influence longitudinal changes in the brain during a
      first episode of psychosis (FEP). METHODS: A 3-year follow-up magnetic resonance
      imaging (MRI) study was performed. Fifty-nine minimally medicated patients who
      were experiencing FEP and 14 healthy control individuals underwent genotyping and
      structural brain MRI at baseline and at 1- and 3-year follow-up. A comparison of
      brain volumes, gray matter, white matter (WM), lateral ventricles (LV), cortical
      cerebrospinal fluid, and thalamus and caudate was made between the groups
      according to their genotype. RESULTS: In patients, the SNP8NRG6221533 risk C
      allele was significantly associated with increased LV volume across time. C
      allele carriers had significantly less WM compared with subjects homozygous for
      the T allele after the follow-up. No other significant differences were observed
      among subgroups. No significant changes according to the genotypes were found in
      healthy individuals. CONCLUSION: Our findings suggest that variations of
      neurodevelopment-related genes, such as the NRG1 gene, can contribute to brain
      abnormalities described in early phases of schizophrenia and progressive changes
      during the initial years of the illness. To our knowledge, it is the first time
      that a relation between NRG1 polymorphisms and longitudinal brain changes is
      reported. (c) 2015 S. Karger AG, Basel.

PMID- 25871613
TI  - Improved Prediction of CYP-Mediated Metabolism with Chemical Fingerprints.
AB  - Molecule and atom fingerprints, similar to path-based Daylight fingerprints, can
      substantially improve the accuracy of P450 site-of-metabolism prediction models.
      Only two chemical fingerprints have been used in metabolism prediction, so little
      is known about the importance of fingerprint parameters on site of metabolism
      predictions. It is possible that different fingerprints might yield more accurate
      models. Here, we study if tuning fingerprints to specific site of metabolism data
      sets can lead to improved models. We measure the impact of 484 specific chemical
      fingerprints on the accuracy of P450 site-of-metabolism prediction models on nine
      P450 isoform site of metabolism data sets. Using a range of search depths, we
      study path, circular, and subgraph fingerprints. Two different labelings, also,
      are considered, both standard SMILES labels and also a labeling that marks ring
      bonds differently than nonring bonds, enabling ortho, para, and meta positioning
      of substituents to be more clearly encoded. Optimal fingerprint models chosen by
      cross-validation performance on the full training data are, on average, 3.8% (Top
      2; percent of molecules with a site of metabolism in the top two predictions) and
      1.4% (AUC; area under the ROC curve) more accurate than base fingerprint models.
      These gains represent, respectively, a 25.6% and 16.7% reduction in error. A more
      rigorous assessment selects fingerprints within each cross-validation fold,
      sometimes selecting different fingerprints for different folds, but yielding a
      more reliable estimate of generalization error. In this assessment, averaging the
      scores from the top few fingerprints yields performances improvements of, on
      average, 3.0% (Top-2) and 0.7% (AUC). These gains are statistically significant
      and represent, respectively, a 20.1% and 8.8% reduction in error. Between
      different isoforms, not many consistencies were observed among the top performing
      fingerprints, with different fingerprints working best for different isoforms.
      These results suggest that there are important gains achievable in site of
      metabolism modeling by including and optimizing atom and molecule fingerprints.
      The optimal site of metabolism models determined by this approach are available
      for use at http://swami.wustl.edu/.

PMID- 25871614
TI  - Pediatric non-Hodgkin lymphomas: first report from Central Africa.
AB  - BACKGROUND: Information on presentation and outcome of pediatric non-Hodgkin's
      lymphoma is limited from Africa. The demographic characteristics, distribution of
      different subtypes were noted and compared with published reports from other
      parts of the world. METHODS: The study was conducted in Kinshasa, the Democratic
      Republic of Congo between January 2002 and December 2012. RESULTS: A total of 63
      cases of pediatric non-Hodgkin's lymphoma were retrospectively analyzed. This
      cohort represents the largest series of pediatric non-Hodgkin's lymphoma
      presented from sub-Saharan Africa. Median age was 8.7+/-3.6 years. There were 43
      (68.3%) males. A mean of 82 +/- 59 days passed from detection of the first sign
      to referral to oncology unit. Morphology distribution showed that 42 cases
      (66.7%) had a diagnosis of Burkitt lymphoma, 16 cases (25.4%) had diffuse large B
      cell lymphoma and 5 cases (7.9%) had NHL-not otherwise specified. The majority of
      patients (82.5%) had advanced stage (stage III and IV). Immunohistochemistry
      findings were available for 32 biopsy samples. All (100%) cases were B-cell non
      Hodgkin's lymphoma and immunohistochemistry had identified 18 (56.3%) cases of
      Burkitt lymphoma. In our cohort, 22 of 32 cases expressed positive bcl-2 and 12
      (37.5%) were found to be positive for bcl-6. Thirty-one (96.7%) cases were
      positive for high Ki-67 antigen expression. Assuming that cases lost to follow-up
      worsened and died, the mortality would be 98.4%. CONCLUSION: In comparison to
      western data, we observed higher proportion of B-cell non-Hodgkin's lymphoma,
      Burkitt Lymphoma and patients with bcl-2 expression.

PMID- 25871616
TI  - Helicobacter pylori CagA Translocation Is Closely Associated With the Expression
      of CagA-signaling Molecules in Low-grade Gastric Mucosa-associated Lymphoid
      Tissue Lymphoma.
AB  - We previously reported that the direct contact of Helicobacter pylori (HP) and B
      cells results in CagA translocation into the latter and that the translocated
      CagA regulates intracellular signaling pathways. Similarly, we recently found
      that CagA does exist in the malignant B cells of gastric mucosa-associated
      lymphoid tissue (MALT) lymphoma and that its presence is closely associated with
      HP dependence. In this study, we further evaluated whether CagA expression
      regulates signal transduction molecules in the tumor cells and further
      contributes to the lymphomagenesis of HP-dependent growth of gastric MALT
      lymphoma. Forty-seven patients with stage IE HP-positive gastric MALT lymphoma
      who received HP eradication as their frontline therapy were included. The
      expression of CagA and signaling pathway-related proteins, such as phospho-SHP-2
      (p-SHP-2), p-ERK, p-p38 MAPK, Bcl-2, and Bcl-xL, in tumor cells was evaluated by
      immunohistochemistry. There were 25 HP-dependent and 22 HP-independent cases. We
      observed that the CagA expression rate was significantly higher in HP-dependent
      than in HP-independent tumors (72% [18/25] vs. 18.2% [4/22]; P<0.001). The
      expression of CagA was closely associated with p-SHP-2 (P=0.012), p-ERK
      (P=0.002), p-p38 MAPK (P=0.006), Bcl-2 (P=0.020), and Bcl-xL (P=0.006)
      expression. Spearman correlation coefficient analysis showed a strong correlation
      between CagA and signaling molecule expression. Combined CagA expression, p-SHP-2
      expression, and p-ERK expression showed an increased positive predictive value
      (93.3% [14/15] vs. 81.8% [18/22]) and an increased specificity (95.5% [21/22] vs.
      81.8% [18/22]) for HP dependence compared with CagA expression alone. Our results
      indicate that CagA protein expression is biologically relevant and is associated
      with the activation of its downstream signals in HP-dependent gastric MALT
      lymphoma. 

PMID- 25871617
TI  - A Comparative Clinicopathologic Study of Collagenous Gastritis in Children and
      Adults: The Same Disorder With Associated Immune-mediated Diseases.
AB  - Collagenous gastritis is a rare condition characterized by surface epithelial
      damage, subepithelial collagen deposition, and a lamina propria inflammatory
      infiltrate. Previous studies have proposed 2 clinicopathologic subtypes: (1)
      children (18 y of age or younger) presenting with severe anemia, nodular gastric
      mucosa, and isolated gastric disease; and (2) adults with chronic watery diarrhea
      that is associated with diffuse collagenous involvement of the gastrointestinal
      tract. However, notable exceptions exist. In fact, broad variability in clinical
      presentation, etiology, treatment and disease course has been reported. To better
      define the clinicopathologic features of collagenous gastritis, we have collected
      10 pediatric and 21 adult cases and describe their clinical, endoscopic,
      pathologic, and follow-up findings. Both children and adults presented with
      similar clinical symptoms such as anemia (50%, 35%, respectively),
      epigastric/abdominal pain (50%, 45%), and diarrhea (40%, 55%). Concomitant immune
      disorders were identified in 2 (20%) children and 3 (14%) adults. Further, 7 of
      17 (41%) adults were taking medications associated with other immune-related
      gastrointestinal diseases including olmesartan and antidepressants.
      Histologically, there were no differences between children and adults with
      collagenous gastritis in the location of gastric involvement, mean collagenous
      layer thickness, and prominence of eosinophils (P>0.05). Extragastric collagenous
      involvement was also seen with comparable frequencies in each cohort (44%, 59%).
      Follow-up information was available for 22 of 31 (71%) patients and ranged from 2
      to 122 months (mean, 33.6 mo). Despite medical management in most cases,
      persistence of symptoms or collagenous gastritis on subsequent biopsies was seen
      in 100% of children and 82% of adults. Of note, treatment for 1 adult patient
      involved cessation of olmesartan resulting in resolution of both symptoms and
      subepithelial collagen deposition on subsequent biopsies. Contrary to prior
      reports, no clinicopathologic differences were identified among pediatric and
      adult patients with collagenous gastritis. Whereas collagenous gastritis remains
      an enigmatic condition, our findings suggest that immune abnormalities and
      medications, such as olmesartan, may be possible triggers. However, current
      treatment options have had limited success and, thus, highlight the need for
      improved therapeutic regimens. 

PMID- 25871618
TI  - NKX6-1 Is a Novel Immunohistochemical Marker for Pancreatic and Duodenal
      Neuroendocrine Tumors.
AB  - NKX6-1 is a homeobox transcription factor participating in the development and
      regulation of endocrine function of pancreatic islets. This study evaluated the
      potential use of NKX6-1 as a diagnostic marker for well-differentiated
      neuroendocrine tumors (WDNETs). In total, 178 primary and 26 metastatic WDNETs of
      different origins were analyzed through immunohistochemistry for NKX6-1, TTF-1,
      CDX2, ISL1, and polyclonal PAX8. NKX6-1 was expressed in 36 of the 44 (82%)
      primary pancreatic WDNETs, 12 of the 18 (67%) primary duodenal WDNETs, and rarely
      in pulmonary, gastric, and appendiceal WDNETs. The specificity of using NKX6-1 as
      a marker for pancreatic and duodenal WDNETs is 93%. Of the 26 metastatic WDNETs,
      NKX6-1 was expressed only in the tumors of pancreatic origin (sensitivity: 63%,
      specificity: 100%). The combinatorial use of NKX6-1, CDX2, TTF-1, and ISL1
      distinguished WDNETs of different origins with high specificity. Our results
      indicated that the inclusion of NKX6-1 in an immunohistochemical panel will be
      beneficial for identifying the primary sites of WDNETs. 

PMID- 25871619
TI  - Gross appearance of multifocal fibrosing thyroiditis.

PMID- 25871620
TI  - Reflex estrogen receptor/progesterone receptor/human epidermal growth factor
      receptor 2 (ER/PR/Her2) analysis of breast cancers in needle core biopsy
      specimens dramatically increases health care costs.
AB  - ER/PR/Her2 are often reflexively assessed in all core needle biopsies (CNBXs)
      containing invasive mammary carcinoma (IMC) so that neoadjuvant therapy can be
      considered. ER/PR/Her2 can be heterogenous, and there is growing consensus that
      negative results for any of these markers in small CNBXs should be repeated in
      larger excision specimens (EXS). The frequency and added cost of repeat testing
      of EXS containing untreated IMC with negative ER/PR/Her2 CNBX results has not
      previously been studied. We reviewed 198 CNBXs containing IMC, which had reflex
      ER/PR/Her2 testing and for which there was an EXS for review. We determined the
      number of cases in which ER/PR/Her2 immunohistochemistry and Her2 fluorescence in
      situ hybridization were negative on CNBX. Twenty-seven (13.6%) patients received
      neoadjuvant chemotherapy, and 8 (4%) patients did not have IMC on follow-up EXS,
      so for them testing the CNBX was necessary. Of the remaining 163 IMCs, 17% were
      ER negative, and 26% were PR negative, whereas 85% were Her2 negative or
      equivocal. At our institution, ER/PR were repeated on slightly more than one half
      of ER/PR-negative tumors, whereas Her2 was repeated on less than one third of
      Her2-negative/equivocal tumors. Had all negative tests been repeated, the
      increased cost of testing both the CNBX and EXS would be $100,821. Extrapolating
      to 230,000 new cases of IMC in the United States each year, the increased cost of
      repeat testing of all negative ER/PR/Her2 CNBX results would be >$117 million
      dollars. Limiting reflex testing to ER would decrease the cost of repeat testing
      to $10 million dollars. We suggest that ER/PR/Her2 should not be reflexively
      performed on all CNBX specimens containing IMC but instead be routinely performed
      on EXS and only selectively on CNBX specimens if neoadjuvant chemotherapy is a
      serious consideration for that individual patient. 

PMID- 25871621
TI  - Germline MLH1 Mutations Are Frequently Identified in Lynch Syndrome Patients With
      Colorectal and Endometrial Carcinoma Demonstrating Isolated Loss of PMS2
      Immunohistochemical Expression.
AB  - Current guidelines on germline mutation testing for patients suspected of having
      Lynch syndrome are not entirely clear in patients with tumors demonstrating
      isolated loss of PMS2 immunohistochemical expression. We analyzed the clinical
      and pathologic features of patients with tumors demonstrating isolated loss of
      PMS2 expression in an attempt to (1) determine the frequency of germline MLH1 and
      PMS2 mutations and (2) correlate mismatch-repair protein immunohistochemistry and
      tumor histology with germline mutation results. A total of 3213 consecutive
      colorectal carcinomas and 215 consecutive endometrial carcinomas were
      prospectively analyzed for DNA mismatch-repair protein expression by
      immunohistochemistry. In total, 32 tumors from 31 patients demonstrated isolated
      loss of PMS2 immunohistochemical expression, including 16 colorectal carcinomas
      and 16 endometrial carcinomas. Microsatellite instability (MSI) polymerase chain
      reaction was performed in 29 tumors from 28 patients with the following results:
      28 tumors demonstrated high-level MSI, and 1 tumor demonstrated low-level MSI.
      Twenty of 31 (65%) patients in the study group had tumors demonstrating
      histopathology associated with high-level MSI. Seventeen patients underwent
      germline mutation analysis with the following results: 24% with MLH1 mutations,
      35% with PMS2 mutations, 12% with PMS2 variants of undetermined significance, and
      29% with no mutations in either MLH1 or PMS2. Three of the 4 patients with MLH1
      germline mutations had a mutation that results in decreased stability and
      quantity of the MLH1 protein that compromises the MLH1-PMS2 protein complex,
      helping to explain the presence of immunogenic but functionally inactive MLH1
      protein within the tumor. The high frequency of MLH1 germline mutations
      identified in our study has important implications for testing strategies in
      patients suspected of having Lynch syndrome and indicates that patients with
      tumors demonstrating isolated loss of PMS2 expression without a germline PMS2
      mutation must have MLH1 mutation analysis performed. 

PMID- 25871622
TI  - Immunohistochemical Comparison of Ovarian and Uterine Endometrioid Carcinoma,
      Endometrioid Carcinoma With Clear Cell Change, and Clear Cell Carcinoma.
AB  - Accurate distinction of clear cell carcinoma (CCC) from endometrioid carcinoma
      (EC) has important clinical implications, but, not infrequently, EC demonstrates
      clear cell change (EC-CC), mimicking CCC. We examined whether a panel of
      immunomarkers can help distinguish between these tumors. Sixty-four CCCs (40
      ovarian and 24 uterine), 34 ECs (21 ovarian and 13 uterine), and 34 EC-CCs (6
      ovarian and 28 uterine) were stained for HNF1beta, BAF250a, Napsin A, ER, and PR.
      Intensity and extent of immunoreactivity was assessed. Fifty-seven of 64 (89%)
      CCCs, 14/34 (41%) EC-CCs, and 16/34 (47%) ECs expressed HNF1beta, and 56/64 (88%)
      CCCs, 4/34 (12%) EC-CCs, and 1/34 (3%) ECs stained for Napsin A. Most CCCs
      demonstrated at least moderate and diffuse staining for both markers, whereas
      only focal and weak expression was identified in most EC-CC/EC. Compared to
      HNF1beta, Napsin A showed increased specificity (93.0% vs. 55.9%, P<0.0001) and
      similar sensitivity (87.5% vs. 89.1%) in distinguishing CCC from EC-CC/EC.
      Thirteen of 64 (20%) CCCs, 6/34 (18%) EC-CCs, and 2/34 (6%) ECs showed loss of
      BAF250a. ER was expressed by 10/64 (16%) CCCs, 30/34 (88%) EC-CCs, and 33/34
      (97%) ECs, whereas PR positivity was identified in 9/64 (14%) CCCs, 26/34 (77%)
      EC-CCs, and 33/34 (97%) ECs. The majority of EC and EC-CC demonstrated diffuse
      staining for ER/PR, whereas most CCCs showed very focal positivity. There is a
      statistically significant difference in HNF1beta, Napsin A, ER, and PR
      immunoexpression between CCC and EC/EC-CC, with Napsin A being a more specific
      marker for CCC than HNF1beta. Overall, the immunoprofile of EC-CC is more
      comparable to that of EC than CCC. The use of a panel of immunostains can help
      distinguish EC-CC from CCC. 

PMID- 25871623
TI  - Reevaluation and reclassification of resected lung carcinomas originally
      diagnosed as squamous cell carcinoma using immunohistochemical analysis.
AB  - Currently, non-small cell lung carcinomas are primarily classified by light
      microscopy. However, recent studies have shown that poorly differentiated tumors
      are more accurately classified by immunohistochemistry. In this study, we
      investigated the use of immunohistochemical analysis in reclassifying lung
      carcinomas that were originally diagnosed as squamous cell carcinoma. Tumor
      slides and blocks were available for histologic evaluation, and tissue
      microarrays were constructed from 480 patients with resected lung carcinomas
      originally diagnosed as squamous cell carcinoma between 1999 and 2009.
      Immunohistochemical analyses for p40, p63, thyroid transcription factor-1 (TTF-1;
      clones SPT24 and 8G7G3/1), napsin A, chromogranin A, synaptophysin, and CD56 were
      performed. Staining intensity (weak, moderate, or strong) and distribution (focal
      or diffuse) were also recorded. Of all, 449 (93.5%) patients were confirmed as
      having squamous cell carcinomas; the cases were mostly diffusely positive for p40
      and negative for TTF-1 (8G7G3/1). Twenty cases (4.2%) were reclassified as
      adenocarcinoma, as they were positive for TTF-1 (8G7G3/1 or SPT24) with either no
      or focal p40 expression, and all of them were poorly differentiated with squamoid
      morphology. In addition, 1 case was reclassified as adenosquamous carcinoma, 4
      cases as large cell carcinoma, 4 cases as large cell neuroendocrine carcinoma,
      and 2 cases as small cell carcinoma. In poorly differentiated non-small cell lung
      carcinomas, an accurate distinction between squamous cell carcinoma and
      adenocarcinoma cannot be reliably determined by morphology alone and requires
      immunohistochemical analysis, even in resected specimens. Our findings suggest
      that TTF-1 8G7G3/1 may be better suited as the primary antibody in
      differentiating adenocarcinoma from squamous cell carcinoma. 

PMID- 25871624
TI  - Heart failure prognosis: comorbidities matter.
AB  - BACKGROUND: Prior risk prediction models have included a selective group of broad
      comorbidities in scoring prognosis of heart failure (HF) patients. OBJECTIVE: We
      examined whether scoring a comprehensive set of comorbidities separately, could
      improve the performance and accuracy of predicting HF prognosis. METHODS: This is
      a cross-validated, longitudinal, retrospective, observational study. Data were
      collected on 602,050 unique HF patients, who received care through the Veterans
      Administration (VA) between October 1, 2006 and September 31, 2011. The dependent
      variable was mortality in six months. The independent variables were all
      International Classification of Disease (ICD) comorbidities, without grouping
      into broad disease categories. RESULTS: The area under the receiver-operating
      curve (AROC) for the multimorbidity (MM) index was 0.784 (95% confidence interval
      [CI]: 0.781-0.786). The MM index was significantly (alpha <0.05) more accurate
      than the Quan variant of the Charlson Index (AROC=0.656), the comorbidity
      categories within the Care Assessment of Need (CAN) Index (AROC=0.677), the von
      Walraven variant of the Elixhauser Index (AROC=0.639), chronological age
      (AROC=0.649), or ejection fraction (EF) (AROC=0.533). CONCLUSION: Inclusion of
      additional comorbidities improves the accuracy of HF prognostic indices. Future
      studies are needed to drive HF prognostic indices with the MM index as a
      component.

PMID- 25871625
TI  - Leadership and cultural competence of healthcare professionals: a social network
      analysis.
AB  - BACKGROUND: International migration is a global phenomenon challenging healthcare
      professionals to provide culturally competent care. OBJECTIVES: The purpose of
      this study was to investigate the influence of leaders on the cultural competence
      of healthcare professionals. METHODS: A cross-sectional survey was conducted from
      2010 to 2012 to obtain data for a social network analysis in 19 inpatient
      services and five primary care services in Belgium. The Competences in Ethnicity
      and Health questionnaire was used. A total of 507 healthcare professionals,
      including 302 nurses, identified their social relationships with other healthcare
      professionals working in their service. Highest in-degree centrality was used to
      identify the leaders within each health service. Multiple regressions with the
      Huber sandwich estimator were used to link cultural competence of leaders with
      the cultural competence of the rest of the healthcare staff. RESULTS: Cultural
      competence of the healthcare staff was associated with the cultural competence of
      the leaders. This association remained significant for two specific domains of
      cultural competence-mediation and paradigm-after controlling for contextual and
      sociodemographic variables. Interaction analysis suggested that the leadership
      effect varied with the degree of cultural competence of the leaders. DISCUSSION:
      Cultural competence among healthcare professionals is acquired partly through
      leadership. Social relationships and leadership effects within health services
      should be considered when developing and implementing culturally competent
      strategies. This requires a cautious approach as the most central individuals are
      not always the same persons as the formal leaders.

PMID- 25871626
TI  - Blood Metabolome Changes Before and After Bariatric Surgery: A (1)H NMR-Based
      Clinical Investigation.
AB  - Excessive body fat and obesity have adverse health effects and result in
      significant morbidity such as type 2 diabetes mellitus. The health burden of
      obesity can be reduced with the Roux-en-Y gastric bypass (RYGB) weight-loss
      bariatric surgery. Little is known on the molecular changes that occur at the
      metabolome level before and after bariatric surgery, with a view to clinical
      biomarker development. Hence, we employed a metabolomics approach in 10 obese
      diabetic patients who underwent bariatric surgery. Metabolomics data were
      obtained by T2- and diffusion-edited hydrogen nuclear magnetic resonance ((1)H
      NMR) spectra to monitor the metabolic and lipoprotein profiles, and gas
      chromatography-mass spectrometry (CG-MS) to access the fatty acid profile before
      and 12 months after RYGB. Using hierarchical partial least squares discriminant
      analysis, we found that RYGB induces several key metabolic alterations associated
      with glucose homeostasis, as well as fatty acid and amino acid metabolism. The
      levels of lactate (Krebs' intermediate cycle) decreased after RYGB. The leucine,
      isoleucine, valine, lactate, and glucose levels were higher in the samples before
      RYGB (p<0.05). Additionally, the levels of very low-density lipoprotein,
      unsaturated lipids, and N-acetyl-glycoprotein were higher before RYGB. By
      contrast, levels of the high-density lipoprotein and phosphatidylcholine were
      higher after bariatric surgery. These results collectively offer important
      holistic integrative biology data to develop future clinically relevant
      metabolomics biomarkers related to bariatric surgery in connection with obesity. 

PMID- 25871627
TI  - The language skeleton after dissecting meaning: A functional segregation within
      Broca's Area.
AB  - Broca's area is proposed as a crucial brain area for linguistic computations.
      Language processing goes beyond word-level processing, also implying the
      integration of meaningful information (semantics) with the underlying structural
      skeleton (syntax). There is an on-going debate about the specialisation of the
      subregions of Broca's area-Brodmann areas (BA) 44 and 45-regarding the latter
      aspects. Here, we tested if syntactic information is specifically processed in BA
      44, whereas BA 45 is mainly recruited for semantic processing. We contrasted
      conditions with sentence structure against conditions with random order in two
      fMRI experiments. Besides, in order to disentangle these processes, we
      systematically removed the amount of semantic information available in the
      stimuli. This was achieved in Experiment 1 by replacing meaningful words (content
      words) by pseudowords. Within real word conditions we found broad activation in
      the left hemisphere, including the inferior frontal gyrus (BA 44/45/47), the
      anterior temporal lobe and posterior superior temporal gyrus (pSTG) and sulcus
      (pSTS). For pseudowords we found a similar activation pattern, still involving BA
      45. Among the pseudowords in Experiment 1, we kept those word elements that
      convey meaning like un- in unhappy or -hood in brotherhood (i.e. derivational
      morphology). In Experiment 2 we tested whether the activation in BA 45 was due to
      their presence. We therefore further removed derivational morphology, only
      leaving word elements that determine syntactic structure (i.e. inflectional
      morphology, e.g. the verb ending -s in he paints). Now, in the absence of all
      semantic cues, including derivational morphology, only BA 44 was active.
      Additional analyses showed a selective responsiveness of this area to syntax
      relevant cues. These findings confirm BA 44 as a core area for the processing of
      pure syntactic information. This furthermore suggests that the brain represents
      structural and meaningful aspects of language separately. 

PMID- 25871629
TI  - Longitudinal monitoring of metabolic alterations in cuprizone mouse model of
      multiple sclerosis using 1H-magnetic resonance spectroscopy.
AB  - Non-invasive measures of well-known pathological hallmarks of multiple sclerosis
      (MS) such as demyelination, inflammation and axonal injury would serve as useful
      markers to monitor disease progression and evaluate potential therapies. To this
      end, in vivo localized proton magnetic resonance spectroscopy ((1)H-MRS) provides
      a powerful means to monitor metabolic changes in the brain and may be sensitive
      to these pathological hallmarks. In our study, we used the cuprizone mouse model
      to study pathological features of MS, such as inflammation, de- and
      remyelination, in a highly reproducible manner. C57BL/6J mice were challenged
      with a 0.2% cuprizone diet for 6-weeks to induce demyelination, thereafter the
      mice were put on a cuprizone free diet for another 6weeks to induce spontaneous
      remyelination. We employed in vivo (1)H-MRS to longitudinally monitor metabolic
      changes in the corpus callosum of cuprizone-fed mice during the demyelination
      (weeks 4 and 6) and spontaneous remyelination (week 12) phases. The MRS spectra
      were quantified with LCModel and since the total creatine (tCr) levels did not
      change over time or between groups, metabolite concentrations were expressed as
      ratios relative to tCr. After 4 and 6weeks of cuprizone treatment a significant
      increase in taurine/tCr and a significant reduction in total N
      acetylaspartate/tCr, total choline-containing compounds/tCr and glutamate/tCr
      could be observed compared to mice under normal diet. At week 12, when almost
      full remyelination was established, no statistically significant metabolic
      differences were present between the control and cuprizone group. Our results
      suggest that these metabolic changes may represent sensitive markers for
      cuprizone induced demyelination, axonal injury and inflammation. To the best of
      our knowledge, this is the first longitudinal in vivo (1)H-MRS study that
      monitored biochemical changes in the corpus callosum of cuprizone fed mice. 

PMID- 25871628
TI  - Alterations in cortical thickness development in preterm-born individuals:
      Implications for high-order cognitive functions.
AB  - Very preterm birth (gestational age <33 weeks) is associated with alterations in
      cortical thickness and with neuropsychological/behavioural impairments. Here we
      studied cortical thickness in very preterm born individuals and controls in mid
      adolescence (mean age 15 years) and beginning of adulthood (mean age 20 years),
      as well as longitudinal changes between the two time points. Using univariate
      approaches, we showed both increases and decreases in cortical thickness in very
      preterm born individuals compared to controls. Specifically (1) very preterm born
      adolescents displayed extensive areas of greater cortical thickness, especially
      in occipitotemporal and prefrontal cortices, differences which decreased
      substantially by early adulthood; (2) at both time points, very preterm-born
      participants showed smaller cortical thickness, especially in parahippocampal and
      insular regions. We then employed a multivariate approach (support vector
      machine) to study spatially discriminating features between the two groups, which
      achieved a mean accuracy of 86.5%. The spatially distributed regions in which
      cortical thickness best discriminated between the groups (top 5%) included
      temporal, occipitotemporal, parietal and prefrontal cortices. Within these
      spatially distributed regions (top 1%), longitudinal changes in cortical
      thickness in left temporal pole, right occipitotemporal gyrus and left superior
      parietal lobe were significantly associated with scores on language-based tests
      of executive function. These results describe alterations in cortical thickness
      development in preterm-born individuals in their second decade of life, with
      implications for high-order cognitive processing.

PMID- 25871630
TI  - C-F bond activation by transient phosphenium dications.
AB  - C-F bond cleavage by transient phosphorus(III)-based dications [RP(C(PPh3)2)](2+)
      (4a(2+), R = Ph; 4b(2+), R = 4-F-Ph) is reported. These dications were generated
      by reaction of the corresponding monocationic precursors with excess
      Na[BAr4(Cl)]. Evidence for the existence of transient dicationic species was
      obtained by trapping the dication 4a(2+) with PMe3. According to theoretical
      analysis, the low-lying lowest unoccupied molecular orbitals of these species
      were responsible for the observed activation of C-F bonds. 

PMID- 25871631
TI  - Label-free protein quantification in freshly ejaculated versus post-mating
      spermatophores of the noble crayfish Astacus astacus.
AB  - Crayfish spermatophores are deposited on the body surface of the female during
      mating and remain there for a period of time before fertilization ensues. Post
      mating changes in protein expression level in the noble crayfish Astacus astacus
      spermatophore were quantified. In-gel digestion and high resolution mass
      spectrometry were used for label-free protein quantification. One hundred twelve
      proteins were identified in the spermatophore of noble crayfish. After 7 days of
      storage on the body of the female, 6 proteins were identified in the post-mating
      spermatophore that showed significant up-regulation and 4 significant down
      regulations (p < 0.05, fold change >= 2). The highest rate of up-regulation was
      observed in sodium/hydrogen exchanger, which may indicate the importance of
      intracellular pH adjustment for final maturation of the crayfish spermatozoon.
      The highest rate of down-regulation was observed in histone H2A. This may
      increase chromatin flexibility and facilitate its transfer into the oocyte during
      fertilization. The vitellogenin protein was identified in the crayfish
      spermatophore and its level changed during storage on the body surface of female.
      Extensive proteomic modification of male gametes during storage on the body
      surface of the female suggests post-mating final maturation of the crayfish
      spermatozoon. BIOLOGICAL SIGNIFICANCE: Freshwater crayfish comprise a large and
      diverse group of ecologically and commercially important animals. Molecular
      studies of gametes in the crayfish can provide insight into the complex process
      of reproduction in this diverse group of animals. The results of such studies can
      be used for development of new techniques for artificial reproduction of these
      economically important species.

PMID- 25871633
TI  - Perfluorooctyl Iodide Stimulates Steroidogenesis in H295R Cells via a Cyclic
      Adenosine Monophosphate Signaling Pathway.
AB  - Perfluorinated iodine alkanes (PFIs) are used widely in the organic fluorine
      industry. Increased production of PFIs has caused environmental health concerns.
      To evaluate the potential endocrine-disrupting effect of PFIs, we investigated
      the effects of perfluorooctyl iodide (PFOI) on steroidogenesis in human
      adrenocortical carcinoma cells (H295R). Levels of aldosterone, cortisol, 17beta
      estradiol, and testosterone were measured in H295R culture medium upon treatment
      with perfluorooctanoic acid (PFOA) and PFIs. Expression of 10 steroidogenic genes
      (StAR, HMGR, CYP11A1, 3betaHSD2, 17betaHSD, CYP17, CYP21, CYP11B1, CYP11B2, and
      CYP19) was measured by real-time polymerase chain reaction. Levels of cyclic
      adenosine monophosphate (cAMP) and adenylate cyclase (AC) activity were measured
      to understand the underlying mechanism of steroidogenic perturbations. Levels of
      production of aldosterone, cortisol, and 17beta-estradiol were elevated
      significantly, and the level of testosterone generation decreased upon treatment
      with 100 MUM PFOI. Similar to the effect induced by forskolin (AC activator),
      expression of all 10 genes involved in the synthesis of steroid hormones was
      upregulated significantly upon exposure to 100 MUM PFOI. PFOA had no effect on
      steroid hormone production or steroidogenic gene expression even though it is
      highly structurally similar with PFOI. Therefore, the terminal -CF2I group in
      PFOI could be a critical factor for mediation of steroidogenesis. PFOI increased
      AC activity and cAMP levels in H295R cells, which implied an underlying mechanism
      for the disturbance of steroidogenesis. These data suggest that PFOI may act as
      an AC activator, thereby stimulating steroidogenesis by activating a cAMP
      signaling pathway. 

PMID- 25871632
TI  - CD33-Targeted Lipid Nanoparticles (aCD33LNs) for Therapeutic Delivery of GTI-2040
      to Acute Myelogenous Leukemia.
AB  - CD33-targeted lipid nanoparticles (aCD33LNs) were synthesized for delivery of GTI
      2040, an antisense oligonucleotide (ASO) against the R2 subunit of ribonucleotide
      reductase, to acute myelogenous leukemia (AML). These LNs incorporated a
      deoxycholate-polyethylenimine (DOC-PEI) conjugate, which has shown significant
      activity to facilitate oligonucleotide delivery. Anti-CD33 scFv (aCD33) was added
      as a targeting ligand. The delivery efficiency of this system was investigated
      both in vitro and in vivo. When cells were treated with aCD33LN/GTI-2040,
      significant uptake was observed in CD33 positive Kasumi-1 cells. aCD33LNs loaded
      with GTI-2040 induced significant down-regulation of R2 mRNA and protein levels
      in AML cells. Moreover, aCD33LN/GTI-2040 showed a 15-fold reduction in the IC50
      of antileukemic drug Ara-C in Kasumi-1 cells. In Kasumi-1 xenograft model,
      aCD33LN/GTI-2040 showed significant R2 downregulation compared to LN/GTI-2040.
      Furthermore, aCD33LN/GTI-2040 coadministered with Ara-C was shown to be highly
      effective in tumor growth inhibition and to greatly increase survival time of
      mice bearing Kasumi-1 xenograft tumors. The conjugate DOC-PEI has shown an
      ability to include calcein release from lipid nanoparticles, suggesting a
      potential mechanism contributing to efficient endosome release by DOC-PEI2K.
      These results indicate that aCD33LNs are a highly effective vehicle for the
      therapeutic delivery of antisense agents to AML. 

PMID- 25871634
TI  - Evaluated Kinetics of the Reactions of H and CH3 with n-Alkanes: Experiments with
      n-Butane and a Combustion Model Reaction Network Analysis.
AB  - Presented is a combined experimental and modeling study of the kinetics of the
      reactions of H and CH3 with n-butane, a representative aliphatic fuel.
      Abstraction of H from n-alkane fuels creates alkyl radicals that rapidly
      decompose at high temperatures to alkenes and daughter radicals. In combustion
      and pyrolysis, the branching ratio for attack on primary and secondary hydrogens
      is a key determinant of the initial olefin and radical pool, and results
      propagate through the chemistry of ignition, combustion, and byproduct formation.
      Experiments to determine relative and absolute rate constants for attack of H and
      CH3 have been carried out in a shock tube between 859 and 1136 K for methyl
      radicals and 890 to 1146 K for H atoms. Pressures ranged from 140 to 410 kPa.
      Appropriate precursors are used to thermally generate H and CH3 in separate
      experiments under dilute and well-defined conditions. A mathematical design
      algorithm has been applied to select the optimum experimental conditions. In
      conjunction with postshock product analyses, a network analysis based on the
      detailed chemical kinetic combustion model JetSurf 2 has been applied. Polynomial
      chaos expansion techniques and Monte Carlo methods are used to analyze the data
      and assess uncertainties. The present results provide the first experimental
      measurements of the branching ratios for attack of H and CH3 on primary and
      secondary hydrogens at temperatures near 1000 K. Results from the literature are
      reviewed and combined with the present data to generate evaluated rate
      expressions for attack on n-butane covering 300 to 2000 K for H atoms and 400 to
      2000 K for methyl radicals. Values for generic n-alkanes and related hydrocarbons
      are also recommended. The present experiments and network analysis further
      demonstrate that the C-H bond scission channels in butyl radicals are an order of
      magnitude less important than currently indicated by JetSurf 2. Updated rate
      expressions for butyl radical fragmentation reactions are provided. 

PMID- 25871635
TI  - Alternative futures for Borneo show the value of integrating economic and
      conservation targets across borders.
AB  - Balancing economic development with international commitments to protect
      biodiversity is a global challenge. Achieving this balance requires an
      understanding of the possible consequences of alternative future scenarios for a
      range of stakeholders. We employ an integrated economic and environmental
      planning approach to evaluate four alternative futures for the mega-diverse
      island of Borneo. We show what could be achieved if the three national
      jurisdictions of Borneo coordinate efforts to achieve their public policy targets
      and allow a partial reallocation of planned land uses. We reveal the potential
      for Borneo to simultaneously retain ~50% of its land as forests, protect adequate
      habitat for the Bornean orangutan (Pongo pygmaeus) and Bornean elephant (Elephas
      maximus borneensis), and achieve an opportunity cost saving of over US$43
      billion. Such coordination would depend on enhanced information sharing and
      reforms to land-use planning, which could be supported by the increasingly
      international nature of economies and conservation efforts.

PMID- 25871636
TI  - The possible link between elevated serum levels of epithelial cell-derived
      neutrophil-activating peptide-78 (ENA-78/CXCL5) and autoimmunity in autistic
      children.
AB  - BACKGROUND: In autoimmune disorders, the underlying pathogenic mechanism is the
      formation of antigen-antibody complexes which trigger an inflammatory response by
      inducing the infiltration of neutrophils. Epithelial cell-derived neutrophil
      activating peptide-78 (ENA-78) is a chemokine that recruits and activates
      neutrophils, thus it could play a pathogenic role in inflammation and autoimmune
      disorders. Some autistic children have elevated levels of brain specific auto
      antibodies. We are the first to evaluate serum expression of ENA-78 and its
      relation to antineuronal auto-antibodies in autistic children. METHODS: Serum ENA
      78 and antineuronal auto-antibodies were measured by ELISA test in 62 autistic
      children aged between 4-11 years and 62 health-matched controls. RESULTS: Serum
      levels of ENA-78 were significantly higher in autistic children than healthy
      controls (P < 0.001). Increased serum levels of ENA-78 have been found in 69.35%
      of autistic patients. In addition, autistic children had significantly higher
      percent positivity of serum antineuronal auto-antibodies (64.5%) than healthy
      controls (6.45%), P < 0.001. There was a significant positive association between
      the positivity of serum antineuronal auto-antibodies and the elevated levels of
      serum ENA-78 (P < 0.001) in autistic children. CONCLUSIONS: Serum levels of ENA
      78 were elevated in autistic children and they were significantly associated with
      the increased levels of serum antineuronal auto-antibodies. However, these data
      should be treated with caution until further research is conducted to determine
      the pathogenic role of ENA-78 in autism and its relation to brain specific auto
      antibodies that have been found in some autistic children. The possible
      therapeutic role of ENA-78 antagonist in autistic children should be also
      studied.

PMID- 25871637
TI  - The IRC7 gene encodes cysteine desulphydrase activity and confers on yeast the
      ability to grow on cysteine as a nitrogen source.
AB  - Although cysteine desulphydrase activity has been purified and characterized from
      Saccharomyces cerevisiae, the gene encoding this activity in vivo has never been
      defined. We show that the full-length IRC7 gene, encoded by the YFR055W open
      reading frame, encodes a protein with cysteine desulphydrase activity. Irc7p
      purified to homogeneity is able to utilize l-cysteine as a substrate, producing
      pyruvate and hydrogen sulphide as products of the reaction. Purified Irc7p also
      utilized l-cystine and some other cysteine conjugates, but not l-cystathionine or
      l-methionine, as substrates. We further show that, in vivo, the IRC7 gene is both
      necessary and sufficient for yeast to grow on l-cysteine as a nitrogen source,
      and that overexpression of the gene results in increased H2 S production. Strains
      overexpressing IRC7 are also hypersensitive to a toxic analogue, S-ethyl-l
      cysteine. While IRC7 has been identified as playing a critical role in converting
      cysteine conjugates to volatile thiols that are important in wine aroma, its
      biological role in yeast cells is likely to involve regulation of cysteine and
      redox homeostasis.

PMID- 25871638
TI  - Management of ovarian cancer in 14th gestational week of pregnancy by robotic
      approach with preservation of the fetus.
AB  - The objective of this study is to present a rare case of pregnancy complicated
      with ovarian cancer managed by robotic surgery. A 36-year-old woman suffered from
      sudden onset of lower abdominal pain during her pregnancy at 14 weeks of
      gestation. As malignancy was highly suspected, left salpingo-oophorectomy,
      bilateral pelvic lymph node dissection, and omentectomy were performed by robotic
      approach. The uterus and fetus were preserved. After surgery, 5 courses of
      carboplatin and paclitaxel were given, and the patient was delivered by cesarean
      section at 37 weeks of pregnancy. Follow-up at 18 months showed no signs of
      cancer recurrence. As there is limited report of pregnancy complicated with
      ovarian cancer managed by robotic surgery, we provide this rare case and suggest
      that surgical staging for ovarian malignancy can be safely accomplished by
      robotic approach at 14 weeks of pregnancy.

PMID- 25871639
TI  - Overall response to first-line tyrosine kinase inhibitor and second-line
      chemotherapy is predictive of survival outcome in epidermal growth factor
      receptor-mutated adenocarcinoma.
AB  - BACKGROUND: First-line epidermal growth factor receptor (EGFR) tyrosine kinase
      inhibitors (TKIs) are effective for the treatment of lung adenocarcinoma with an
      EGFR-sensitizing mutation, but resistance is inevitable. Chemotherapy is widely
      used in the second-line setting. The outcome following this treatment scheme has
      not been thoroughly evaluated. METHODS: From 2007 to 2011, consecutive patients
      with mutated EGFR receiving first-line TKI and second-line chemotherapy were
      retrospectively reviewed. The overall response was categorized into double
      responder, single responder and double nonresponder. RESULTS: Following this
      treatment scheme, baseline Eastern Cooperative Oncology Group (ECOG) performance
      status 0-1 (HR 0.60; 95% CI 0.37-0.98; p = 0.041) and double responder (HR 0.24;
      95% CI 0.07-0.78; p = 0.018) were independent predictors of overall survival.
      Absence of pleural metastasis independently predicted the response to first-line
      TKI (OR 2.60; 95% CI 1.13-5.99; p = 0.025). In TKI responders, ECOG performance
      status 0-1 before chemotherapy (OR 4.95; 95% CI 1.15-21.28; p = 0.006), an exon
      19 deletion (OR 4.74; 95% CI 1.30-17.21; p = 0.018) and progression-free survival
      (PFS) on first-line TKI (OR 1.02; 95% CI 1.01-1.09; p = 0.049) independently
      predicted the response to second-line chemotherapy. A moderate linear
      relationship (Pearson's r = 0.441; p = 0.001) existed between the PFS of this
      treatment scheme in TKI responders. CONCLUSION: The status of double responder to
      first-line TKI and second-line chemotherapy was predictive of improved survival
      in EGFR-mutated adenocarcinoma.

PMID- 25871640
TI  - Serum 25-hydroxyvitamin D levels and prognosis in hematological malignancies: a
      systematic review and meta-analysis.
AB  - BACKGROUND/AIMS: Serum 25-hydroxyvitamin D [25(OH)D] levels proved to be
      associated with prognosis of patients with colorectal cancer or breast cancer,
      but its prognostic role in hematological malignancies was still unclear. A
      systematic review and meta-analysis was performed to comprehensively evaluate the
      association between serum 25(OH)D levels and prognosis of patients with
      hematological malignancies. METHODS: We searched Pubmed, Embase, Web of Science,
      and Google Scholar for studies evaluating the association between serum 25(OH)D
      levels and prognosis of patients with hematological malignancies. The hazard
      ratios (HR) with 95% confidence intervals (95%CI) for overall survival (OS) or
      relapse-free survival (RFS) were pooled using meta-analysis. RESULTS: Seven
      studies with a total of 2,643 patients with hematological cancer were finally
      included into the meta-analysis. Overall, compared with normal serum 25(OH)D
      levels, low serum 25(OH)D levels were significantly associated with both poorer
      OS (HR = 1.85, 95% CI 1.54-2.23, P <0.001) and poorer RFS (HR = 1.45, 95% CI 1.25
      to 1.70, P <0.001) in hematological malignancies. Subgroup analysis further
      showed that low serum 25(OH)D levels were significantly associated with poorer OS
      and RFS in both lymphoma and leukemia. CONCLUSION: Low serum 25(OH)D levels are
      significantly associated with poorer prognosis in patients with hematological
      malignancies including lymphoma and leukemia.

PMID- 25871641
TI  - Distal Partial Trisomy 15q26 and Partial Monosomy 16p13.3 in a 36-Year-Old Male
      with Clinical Features of Both Chromosomal Abnormalities.
AB  - We report a 36-year-old Caucasian male identified with distal partial trisomy 15q
      and partial monosomy 16p from an unbalanced chromosome translocation detected by
      microarray and FISH analysis. He had a history of developmental delay and
      intellectual disability, chronic anemia, tall and slender stature, thoracic
      scoliosis and lumbar lordosis, and dysmorphic features. The distal partial
      trisomy 15q included the insulin-like growth factor 1 receptor gene involved with
      growth, while genes in the distal partial monosomy 16p region are involved with
      alpha hemoglobin production, intellectual disability, dysmorphic features, and
      acromegaly. The chromosome derivative found in our patient contains genes known
      to play a role in his phenotype.

PMID- 25871642
TI  - Trichophyton rubrum conidia modulate the expression and transport of Toll-like
      receptor 2 in HaCaT cell.
AB  - Trichophyton rubrum (T. rubrum) represents the most important agent of
      dermatophytosis in humans. T. rubrum infection causes slight inflammation, and
      tends to be chronic and recurrent. It is suggested that T. rubrum can modulate
      the innate immune responses of host cells, which result in the failure of host
      cells to recognize T. rubrum and initiate effective immune responses. In this
      study we show how T. rubrum conidia modulate the expression and transport of Toll
      like receptor 2 in HaCaT cell. Flow cytometric analysis showed that the surface
      and total expression of Toll-like receptor 2 were upregulated at the very early
      stage when keratinocytes were exposed to T. rubrum conidia regardless of the
      dose, and the upregulation of surface TLR2 was much more significant than that of
      total TLR2. Moreover, TLR2 expression was suppressed after upregulation in the
      initial stage of T. rubrum exposure, and the decrease of total TLR2 was earlier
      than that of surface TLR2. Our results suggest that in the early stage, TLR2 of
      keratinocytes were upregulated and transported to the cell surface. After then,
      the expression of TLR2 was suppressed by T. rubrum conidia.

PMID- 25871643
TI  - Proton pump inhibitor use significantly increases the risk of cryptogenic liver
      abscess: a population-based study.
AB  - BACKGROUND: Proton pump inhibitors (PPIs) increase gastric pH and impair defence
      mechanisms against ingested pathogens, which may result in the overgrowth of
      virulent Klebsiella pneumoniae in the intestine and subsequent liver abscess.
      AIM: We investigated the possible association between PPIs use and cryptogenic
      liver abscess in Taiwan. METHODS: We conducted a population-based case-control
      study using data from the National Health Insurance Research Database. A total of
      958 adult cases of liver abscess and 3832 age- and sex-matched control patients
      were enrolled during 2000-2010. Conditional logistic regression was used to
      estimate the adjusted odds ratios (ORs) in patients using PPIs before cryptogenic
      liver abscess. RESULTS: The adjusted OR associating current use of PPIs
      (prescription within the past 30 days) with cryptogenic liver abscess was 4.7
      [95% confidence interval (CI), 2.9-7.8], and recent use of PPIs (prescription
      within the past 31-90 days) with cryptogenic liver abscess was 2.9 (95% CI, 1.4
      6.1). A dose-response relationship was apparent for cumulative dose of PPIs
      within 90 days. Adjusted OR was highest among the patients receiving PPIs more
      than 60 cumulative defined daily dose (OR = 6.5, 95% CI, 2.8-14.9). CONCLUSION:
      Proton pump inhibitor therapy within the past 90 days was associated with an
      increased risk of cryptogenic liver abscess.

PMID- 25871644
TI  - Functional characteristics of spirilloxanthin and keto-bearing Analogues in light
      harvesting LH2 complexes from Rhodobacter sphaeroides with a genetically modified
      carotenoid synthesis pathway.
AB  - Light-harvesting 2 (LH2) complexes from a genetically modified strain of the
      purple photosynthetic bacterium Rhodobacter (Rba.) sphaeroides were studied using
      static and ultrafast optical methods and resonance Raman spectroscopy. Carotenoid
      synthesis in the Rba. sphaeroides strain was engineered to redirect carotenoid
      production away from spheroidene into the spirilloxanthin synthesis pathway. The
      strain assembles LH2 antennas with substantial amounts of spirilloxanthin (total
      double-bond conjugation length N=13) if grown anaerobically and of keto-bearing
      long-chain analogs [2-ketoanhydrorhodovibrin (N=13), 2-ketospirilloxanthin (N=14)
      and 2,2'-diketospirilloxanthin (N=15)] if grown semi-aerobically (with ratios
      that depend on growth conditions). We present the photophysical, electronic, and
      vibrational properties of these carotenoids, both isolated in organic media and
      assembled within LH2 complexes. Measurements of excited-state energy transfer to
      the array of excitonically coupled bacteriochlorophyll a molecules (B850) show
      that the mean lifetime of the first singlet excited state (S1) of the long-chain
      (N>=13) carotenoids does not change appreciably between organic media and the
      protein environment. In each case, the S1 state appears to lie lower in energy
      than that of B850. The energy-transfer yield is ~0.4 in LH2 (from the strain
      grown aerobically or semi-aerobically), which is less than half that achieved for
      LH2 that contains short-chain (N<=11) analogues. Collectively, the results
      suggest that the S1 excited state of the long-chain (N>=13) carotenoids
      participates little if at all in carotenoid-to-BChl a energy transfer, which
      occurs predominantly via the carotenoid S2 excited state in these antennas. 

PMID- 25871645
TI  - The dietary inflammatory index is associated with colorectal cancer in the
      National Institutes of Health-American Association of Retired Persons Diet and
      Health Study.
AB  - Diet is a strong moderator of systemic inflammation, an established risk factor
      for colorectal cancer (CRC). The dietary inflammatory index (DII) measures the
      inflammatory potential of individuals' diets. The association between the DII and
      incident CRC was examined, using the National Institutes of Health-American
      Associations of Retired Persons Diet and Health Study individuals (n 489,422)
      aged 50-74 years at recruitment, starting between 1995-6, and followed for a mean
      of 9.1 (sd 2.9) years. Baseline data from a FFQ were used to calculate the DII;
      higher scores are more pro-inflammatory, and lower scores are more anti
      inflammatory. First, primary CRC diagnoses were identified through linkage to
      state cancer registries. Anatomic location and disease severity also were
      examined. Cox proportional hazards models estimated CRC hazard ratios (HR) and
      95% CI using quartile 1 as the referent. DII quartile 4 compared to quartile 1
      was associated with CRC risk among all subjects (HR 1.40, 95% CI 1.28, 1.53; P
      for trend < 0.01). Statistically significant associations also were observed for
      each anatomic site examined, for moderate and poorly differentiated tumours, and
      at each cancer stage among all subjects. Effects were similar when stratified by
      sex; however, results were statistically significant only in males. The only
      result reaching statistical significance in females was risk of moderately
      differentiated CRC tumours (DII quartile 4 v. quartile 1 HR 1.26, 95% CI 1.03,
      1.56). Overall, the DII was associated with CRC risk among all subjects. The DII
      may serve as a novel way to evaluate dietary risk for chronic disorders
      associated with inflammation, such as CRC.

PMID- 25871646
TI  - Metabolomic Signatures for Drug Response Phenotypes: Pharmacometabolomics Enables
      Precision Medicine.
AB  - The scaling up of data in clinical pharmacology and the merger of systems biology
      and pharmacology has led to the emergence of a new discipline of Quantitative and
      Systems Pharmacology (QSP). This new research direction might significantly
      advance the discovery, development, and clinical use of therapeutic drugs.
      Research communities from computational biology, systems biology, and biological
      engineering--working collaboratively with pharmacologists, geneticists,
      biochemists, and analytical chemists--are creating and modeling large data on
      drug effects that is transforming our understanding of how these drugs work at a
      network level. In this review, we highlight developments in a new and rapidly
      growing field--pharmacometabolomics--in which large biochemical data-capturing
      effects of genome, gut microbiome, and environment exposures is revealing
      information about metabotypes and treatment outcomes, and creating metabolic
      signatures as new potential biomarkers. Pharmacometabolomics informs and
      complements pharmacogenomics and together they provide building blocks for QSP.

PMID- 25871647
TI  - Co-electroplated Kesterite Bifacial Thin-Film Solar Cells: A Study of
      Sulfurization Temperature.
AB  - Earth-abundant material, kesterite Cu2ZnSnS4 (CZTS), demonstrates the tremendous
      potential to serve as the absorber layer for the bifacial thin-film solar cell.
      The exploration of appropriate sulfurization conditions including annealing
      temperature is significant to gain insight into the growth mechanism based on the
      substrates using transparent conductive oxides (TCO) and improve device
      performance. The kesterite solar absorbers were fabricated on ITO substrates by
      sulfurizing co-electroplated Cu-Zn-Sn-S precursors in argon diluted H2S
      atmosphere at different temperatures (475-550  degrees C) for 30 min.
      Experimental proof, including cross-section scanning electron microscopy, X-ray
      photoelectron spectroscopy, X-ray diffraction, UV-vis-NIR transmission spectrum,
      and Raman and far-infrared spectroscopy, is presented for the crystallization of
      CZTS on an ITO substrate and the interfacial reaction between the ITO back
      contact and CZTS absorber. The complete conversion of precursor into CZTS
      requires at least 500  degrees C sulfurization temperature. The aggressive
      interfacial reaction leading to the out-diffusion of In into CZTS to a
      considerable extent, formation of tin sulfides, and electrically conductive
      degradation of ITO back contact occurs at the sulfurization temperatures higher
      than 500  degrees C. The bifacial devices obtained by 520  degrees C
      sulfurization exhibit the best conversion efficiencies and open circuit voltages.
      However, the presence of non-ohmic back contact (secondary diode), the short
      minority lifetime, and the high interfacial recombination rates negatively limit
      the open circuit voltage, fill factor, and efficiency, evidenced by
      illumination/temperature-dependent J-V, frequency-dependent capacitance-voltage
      (C-V-f), time-resolved PL (TRPL), and bias-dependent external quantum efficiency
      (EQE) measurements. 

PMID- 25871648
TI  - Photosynthesis in reproductive structures: costs and benefits.
AB  - The role of photosynthesis by reproductive structures during grain-filling has
      important implications for cereal breeding, but the methods for assessing the
      contribution by reproductive structures to grain-filling are invasive and prone
      to compensatory changes elsewhere in the plant. A technique analysing the natural
      abundance of stable carbon isotopes in soluble carbohydrates has significant
      promise. However, it depends crucially on there being no more than two sources of
      organic carbon (leaf and ear/awn), with significantly different (13)C:(12)C
      ratios and no secondary fractionation during grain-filling. The role of
      additional peduncle carbohydrate reserves represents a potential means for N
      remobilization, as well as for hydraulic continuity during grain-filling. The
      natural abundance of the stable isotopes of carbon and oxygen are also useful for
      exploring the influence of reproduction on whole plant carbon and water relations
      and have been used to examine the resource costs of reproduction in females and
      males of dioecious plants. Photosynthesis in reproductive structures is
      widespread among oxygenic photosynthetic organisms, including many clades of
      algae and embryophytes of different levels of complexity. The possible
      evolutionary benefits of photosynthesis in reproductive structures include
      decreasing the carbon cost of reproduction and 'use' of transpiratory loss of
      water to deliver phloem-immobile calcium Ca(2+) and silicon [Si(OH)4] via the
      xylem. The possible costs of photosynthesis in reproductive structures are
      increasing damage to DNA from photosynthetically active, and hence UV-B,
      radiation and the production of reactive oxygen species. 

PMID- 25871649
TI  - Cell-wall properties contributing to improved deconstruction by alkaline pre
      treatment and enzymatic hydrolysis in diverse maize (Zea mays L.) lines.
AB  - A maize (Zea mays L. subsp. mays) diversity panel consisting of 26 maize lines
      exhibiting a wide range of cell-wall properties and responses to hydrolysis by
      cellulolytic enzymes was employed to investigate the relationship between cell
      wall properties, cell-wall responses to mild NaOH pre-treatment, and enzymatic
      hydrolysis yields. Enzymatic hydrolysis of the cellulose in the untreated maize
      was found to be positively correlated with the water retention value, which is a
      measure of cell-wall susceptibility to swelling. It was also positively
      correlated with the lignin syringyl/guaiacyl ratio and negatively correlated with
      the initial cell-wall lignin, xylan, acetate, and p-coumaric acid (pCA) content,
      as well as pCA released from the cell wall by pre-treatment. The hydrolysis yield
      following pre-treatment exhibited statistically significant negative correlations
      to the lignin content after pre-treatment and positive correlations to the
      solubilized ferulic acid and pCA. Several unanticipated results were observed,
      including a positive correlation between initial lignin and acetate content, lack
      of correlation between acetate content and initial xylan content, and negative
      correlation between each of these three variables to the hydrolysis yields for
      untreated maize. Another surprising result was that pCA release was negatively
      correlated with hydrolysis yields for untreated maize and, along with ferulic
      acid release, was positively correlated with the pre-treated maize hydrolysis
      yields. This indicates that these properties that may negatively contribute to
      the recalcitrance in untreated cell walls may positively contribute to their
      deconstruction by alkaline pre-treatment. 

PMID- 25871651
TI  - Comparing different methods to fix and to dehydrate cells on alginate hydrogel
      scaffolds using scanning electron microscopy.
AB  - Scanning electron microscopy (SEM) is commonly used in the analysis of scaffolds
      morphology, as well as cell attachment, morphology and spreading on to the
      scaffolds. However, so far a specific methodology to prepare the alginate
      hydrogel (AH) scaffolds for SEM analysis has not been evaluated. This study
      compared different methods to fix/dehydrate cells in AH scaffolds for SEM
      analysis. AH scaffolds were prepared and seeded with NIH/3T3 cell line; fixed
      with glutaraldehyde, osmium tetroxide, or the freeze drying method and analyzed
      by SEM. Results demonstrated that the freeze dried method interferes less with
      cell morphology and density, and preserves the scaffolds structure. The fixation
      with glutaraldehyde did not affect cells morphology and density; however, the
      scaffolds morphology was affected in some level. The fixation with osmium
      tetroxide interfered in the natural structure of cells and scaffold. In
      conclusion the freeze drying and glutaraldehyde are suitable methods for cell
      fixation in AH scaffold for SEM, although scaffolds structure seems to be
      affected by glutaraldehyde.

PMID- 25871650
TI  - Ribonuclease J is required for chloroplast and embryo development in Arabidopsis.
AB  - Chloroplasts perform many essential metabolic functions and their proper
      development is critically important in embryogenesis. However, little is known
      about how chloroplasts function in embryogenesis and more relevant components
      need to be characterized. In this study, we show that Arabidopsis Ribonuclease J
      (RNase J) is required for chloroplast and embryo development. Mutation of AtRNJ
      led to albino ovules containing aborted embryos; the morphological development of
      rnj embryos was disturbed after the globular stage. Observation of
      ultrastructures indicated that these aborted embryos may result from impaired
      chloroplast development. Furthermore, by analyzing the molecular markers of cell
      fate decisions (STM, FIL, ML1, SCR, and WOX5) in rnj embryos, we found that this
      impairment of chloroplast development may lead to aberrant embryo patterning
      along the apical-basal axis, indicating that AtRNJ is important in initiating and
      maintaining the organization of shoot apical meristems (SAMs), cotyledons, and
      hypocotyls. Moreover, the transport and response of auxin in rnj embryos was
      found to be disrupted, suggesting that AtRNJ may be involved in auxin-mediated
      pathways during embryogenesis. Therefore, we speculate that RNJ plays a vital
      role in embryo morphogenesis and apical-basal pattern formation by regulating
      chloroplast development. 

PMID- 25871652
TI  - Zebrin II Expression in the Cerebellum of a Paleognathous Bird, the Chilean
      Tinamou (Nothoprocta perdicaria).
AB  - Zebrin II (ZII) is a glycolytic enzyme expressed in cerebellar Purkinje cells. In
      both mammals and birds, ZII is expressed heterogeneously, such that there are
      sagittal stripes of Purkinje cells with a high ZII expression (ZII+) alternating
      with stripes of Purkinje cells with little or no expression (ZII-). To date, ZII
      expression studies are limited to neognathous birds: pigeons (Columbiformes),
      chickens (Galliformes), and hummingbirds (Trochilidae). These previous studies
      divided the avian cerebellum into 5 transverse regions based on the pattern of
      ZII expression. In the lingular region (lobule I) all Purkinje cells are ZII+. In
      the anterior region (lobules II-V) there are 4 pairs of ZII+/- stripes. In the
      central region (lobules VI-VIII) all Purkinje cells are ZII+. In the posterior
      region (lobules VIII-IX) there are 5-7 pairs of ZII+/- stripes. Finally, in the
      nodular region (lobule X) all Purkinje cells are ZII+. As the pattern of ZII
      stripes is quite similar in these disparate species, it appears that it is highly
      conserved. However, it has yet to be studied in paleognathous birds, which split
      from the neognaths over 100 million years ago. To better understand the evolution
      of cerebellar compartmentation in birds, we examined ZII immunoreactivity in a
      paleognath, the Chilean tinamou (Nothoprocta perdicaria). In the tinamou,
      Purkinje cells expressed ZII heterogeneously such that there were sagittal ZII+
      and ZII- stripes of Purkinje cells, and this pattern of expression was largely
      similar to that observed in neognathous birds. For example, all Purkinje cells in
      the lingular (lobule I) and nodular (lobule X) regions were ZII+, and there were
      4 pairs of ZII+/- stripes in the anterior region (lobules II-V). In contrast to
      neognaths, however, ZII was expressed in lobules VI-VII as a series of sagittal
      stripes in the tinamou. Also unlike in neognaths, stripes were absent in lobule
      IXab, and all Purkinje cells expressed ZII in the tinamou. The differences in ZII
      expression between the tinamou and neognaths could reflect behavior, but the
      general similarity of the expression patterns across all bird species suggests
      that ZII stripes evolved early in the avian phylogenetic tree.

PMID- 25871656
TI  - The girls on the bridge: Edvard Munch.

PMID- 25871653
TI  - Preferences for return of incidental findings from genome sequencing among women
      diagnosed with breast cancer at a young age.
AB  - While experts have made recommendations, information is needed regarding what
      genome sequencing results patients would want returned. We investigated what
      results women diagnosed with breast cancer at a young age would want returned and
      why. We conducted 60 semi-structured, in-person individual interviews with women
      diagnosed with breast cancer at age 40 or younger. We examined interest in six
      types of incidental findings and reasons for interest or disinterest in each
      type. Two coders independently coded interview transcripts; analysis was
      conducted using NVivo 10. Most participants were at least somewhat interested in
      all six result types, but strongest interest was in actionable results (i.e.
      variants affecting risk of a preventable or treatable disease and treatment
      response). Reasons for interest varied between different result types. Some
      participants were not interested or ambivalent about results not seen as
      currently actionable. Participants wanted to be able to choose what results are
      returned. Participants distinguished between types of individual genome
      sequencing results, with different reasons for wanting different types of
      information. The findings suggest that a focus on actionable results can be a
      common ground for all stakeholders in developing a policy for returning
      individual genome sequencing results. 

PMID- 25871657
TI  - Is there an app to solve app overload?

PMID- 25871658
TI  - Reforming the World Health Organization after Ebola.

PMID- 25871665
TI  - Regenerative medicine.

PMID- 25871666
TI  - A piece of my mind. The ethics of patient care.

PMID- 25871667
TI  - Keeping personal health information safe: the importance of good data hygiene.

PMID- 25871668
TI  - Association of maternal diabetes with autism in offspring.
AB  - IMPORTANCE: Information about the association of maternal diabetes and autism
      spectrum disorders (ASDs) in offspring is limited, with no report on the
      importance of timing of exposure during gestation. OBJECTIVE: To assess ASD risk
      associated with intrauterine exposure to preexisting type 2 diabetes and
      gestational diabetes mellitus (GDM) by gestational age at GDM diagnosis. DESIGN,
      SETTING, AND PATIENTS: Retrospective longitudinal cohort study including 322 323
      singleton children born in 1995-2009 at Kaiser Permanente Southern California
      (KPSC) hospitals. Children were tracked from birth until the first of the
      following: date of clinical diagnosis of ASD, last date of continuous KPSC health
      plan membership, death due to any cause, or December 31, 2012. Relative risks of
      ASD were estimated by hazard ratios (HRs) using Cox regression models adjusted
      for birth year. EXPOSURES: Maternal preexisting type 2 diabetes (n = 6496), GDM
      diagnosed at 26 weeks' gestation or earlier (n = 7456) or after 26 weeks'
      gestation (n = 17 579), or no diabetes (n = 290 792) during the index pregnancy.
      MAIN OUTCOMES AND MEASURES: Clinical diagnosis of ASD in offspring. RESULTS:
      During follow-up, 3388 children were diagnosed as having ASD (115 exposed to
      preexisting type 2 diabetes, 130 exposed to GDM at <=26 weeks, 180 exposed to GDM
      at >26 weeks, and 2963 unexposed). Unadjusted annual ASD incidences were 3.26,
      3.02, 1.77, and 1.77 per 1000 among children of mothers with preexisting type 2
      diabetes, GDM diagnosed at 26 weeks or earlier, GDM diagnosed after 26 weeks, and
      no diabetes, respectively. The birth year-adjusted HRs were 1.59 (95% CI, 1.29
      1.95) for preexisting type 2 diabetes, 1.63 (95% CI, 1.35-1.97) for GDM diagnosed
      at 26 weeks or earlier, and 0.98 (95% CI, 0.84-1.15) for GDM diagnosed after 26
      weeks relative to no exposure. After adjustment for maternal age, parity,
      education, household income, race/ethnicity, history of comorbidity, and sex of
      the child, maternal preexisting type 2 diabetes was not significantly associated
      with risk of ASD in offspring (HR, 1.21; 95% CI, 0.97-1.52), but GDM diagnosed at
      26 weeks or earlier remained so (HR, 1.42; 95% CI, 1.15-1.74). Antidiabetic
      medication exposure was not independently associated with ASD risk. Adjustment
      for a mother or older sibling with ASD in the full cohort and for maternal
      smoking, prepregnancy body mass index, and gestational weight gain in the subset
      with available data (n = 68 512) did not affect the results. CONCLUSIONS AND
      RELEVANCE: In this large, multiethnic clinical cohort of singleton children born
      at 28 to 44 weeks' gestation, exposure to maternal GDM diagnosed by 26 weeks'
      gestation was associated with risk of ASD in offspring.

PMID- 25871669
TI  - Survival and outcomes following bioprosthetic vs mechanical mitral valve
      replacement in patients aged 50 to 69 years.
AB  - IMPORTANCE: In nonelderly patients with mitral disease requiring valve
      replacement, deciding between bioprosthetic and mechanical prosthetic valves is
      challenging because long-term survival and morbidity are not well defined.
      OBJECTIVE: To quantify survival and major morbidity after mitral valve
      replacement in patients aged 50 to 69 years. DESIGN, SETTING, AND PARTICIPANTS:
      Retrospective cohort analysis of 3433 patients (aged 50-69 years) who underwent
      primary, isolated mitral valve replacement in New York State hospitals from 1997
      2007. Follow-up ended November 30, 2013; median duration was 8.2 years (range, 0
      16.8 years). Propensity score matching for 19 baseline characteristics yielded
      664 patient pairs. EXPOSURES: Bioprosthetic vs mechanical prosthetic mitral valve
      replacement. MAIN OUTCOMES AND MEASURES: All-cause mortality, stroke,
      reoperation, and major bleeding events. RESULTS: No survival difference was
      observed between use of mechanical prosthetic and bioprosthetic mitral valves in
      patients aged 50 to 69 years matched by propensity score or in a subgroup
      analysis of age by decade. Among patients matched by propensity score, the
      incidences of stroke and bleeding events were both significantly higher in those
      who received mechanical prosthetic mitral valves compared with those who received
      bioprosthetic mitral valves; however, the incidence of reoperation was lower in
      the mechanical prosthesis group compared with the bioprosthesis group. [table:
      see text] CONCLUSIONS AND RELEVANCE: Among patients aged 50 to 69 years
      undergoing mitral valve replacement in New York State, there was no significant
      survival difference at 15 years in patients matched by propensity score who
      underwent mechanical prosthetic vs bioprosthetic mitral valve replacement.
      Mechanical prosthetic valves were associated with lower risk of reoperation but
      greater risk of bleeding and stroke. Even though these findings suggest
      bioprosthetic mitral valve replacement may be a reasonable alternative to
      mechanical prosthetic valve replacement in patients aged 50 to 69 years, the 15
      year follow-up was insufficient to fully assess lifetime risks, particularly of
      reoperation.

PMID- 25871671
TI  - Acute stroke intervention: a systematic review.
AB  - IMPORTANCE: Acute ischemic stroke is a major cause of mortality and morbidity in
      the United States. We review the latest data and evidence supporting catheter
      directed treatment for proximal artery occlusion as an adjunct to intravenous
      thrombolysis in patients with acute stroke. OBJECTIVE: To review the
      pathophysiology of acute brain ischemia and infarction and the evidence
      supporting various stroke reperfusion treatments. EVIDENCE REVIEW: Systematic
      literature search of MEDLINE databases published between January 1, 1990, and
      February 11, 2015, was performed to identify studies addressing the role of
      thrombolysis and mechanical thrombectomy in acute stroke management. Studies
      included randomized clinical trials, observational studies, guideline statements,
      and review articles. Sixty-eight articles (N = 108,082 patients) were selected
      for review. FINDINGS: Intravenous thrombolysis is the mainstay of acute ischemic
      stroke management for any patient with disabling deficits presenting within 4.5
      hours from symptom onset. Randomized trials have demonstrated that more patients
      return to having good function (defined by being independent and having slight
      disability or less) when treated within 4.5 hours after symptom onset with
      intravenous recombinant tissue plasminogen activator (IV rtPA) therapy.
      Mechanical thrombectomy in select patients with acute ischemic stroke and
      proximal artery occlusions has demonstrated substantial rates of partial or
      complete arterial recanalization and improved outcomes compared with IV rtPA or
      best medical treatment alone in multiple randomized clinical trials. Regardless
      of mode of reperfusion, earlier reperfusion is associated with better clinical
      outcomes. CONCLUSIONS AND RELEVANCE: Intravenous rtPA remains the standard of
      care for patients with moderate to severe neurological deficits who present
      within 4.5 hours of symptom onset. Outcomes for some patients with acute ischemic
      stroke and moderate to severe neurological deficits due to proximal artery
      occlusion are improved with endovascular reperfusion therapy. Efforts to hasten
      reperfusion therapy, regardless of the mode, should be undertaken within
      organized stroke systems of care.

PMID- 25871670
TI  - Site-level variation in and practices associated with dabigatran adherence.
AB  - IMPORTANCE: Unlike warfarin, which requires routine laboratory testing and dose
      adjustment, target-specific oral anticoagulants like dabigatran do not. However,
      optimal follow-up infrastructure and modifiable site-level factors associated
      with improved adherence to dabigatran are unknown. OBJECTIVES: To assess site
      level variation in dabigatran adherence and to identify site-level practices
      associated with higher dabigatran adherence. DESIGN, SETTING, AND PARTICIPANTS:
      Mixed-methods study involving retrospective quantitative and cross-sectional
      qualitative data. A total of 67 Veterans Health Administration sites with 20 or
      more patients filling dabigatran prescriptions between 2010 and 2012 for
      nonvalvular atrial fibrillation were sampled (4863 total patients; median, 51
      patients per site). Forty-seven pharmacists from 41 eligible sites participated
      in the qualitative inquiry. EXPOSURE: Site-level practices identified included
      appropriate patient selection, pharmacist-driven patient education, and
      pharmacist-led adverse event and adherence monitoring. MAIN OUTCOMES AND
      MEASURES: Dabigatran adherence (intensity of drug use during therapy) defined by
      proportion of days covered (ratio of days supplied by prescription to follow-up
      duration) of 80% or more. RESULTS: The median proportion of patients adherent to
      dabigatran was 74% (interquartile range [IQR], 66%-80%). After multivariable
      adjustment, dabigatran adherence across sites varied by a median odds ratio of
      1.57. Review of practices across participating sites showed that appropriate
      patient selection was performed at 31 sites, pharmacist-led education was
      provided at 30 sites, and pharmacist-led monitoring at 28 sites. The proportion
      of adherent patients was higher at sites performing appropriate selection (75% vs
      69%), education (76% vs 66%), and monitoring (77% vs 65%). Following
      multivariable adjustment, association between pharmacist-led education and
      dabigatran adherence was not statistically significant (relative risk [RR], 0.94;
      95% CI, 0.83-1.06). Appropriate patient selection (RR, 1.14; 95% CI, 1.05-1.25),
      and provision of pharmacist-led monitoring (RR, 1.25; 95% CI, 1.11-1.41) were
      associated with better patient adherence. Additionally, longer duration of
      monitoring and providing more intensive care to nonadherent patients in
      collaboration with the clinician improved adherence. CONCLUSIONS AND RELEVANCE:
      Among nonvalvular atrial fibrillation patients treated with dabigatran, there was
      variability in patient medication adherence across Veterans Health Administration
      sites. Specific pharmacist-based activities were associated with greater patient
      adherence to dabigatran.

PMID- 25871672
TI  - Comprehensive injury research.

PMID- 25871673
TI  - FDG-PET/CT imaging for mediastinal staging in patients with potentially
      resectable non-small cell lung cancer.
AB  - CLINICAL QUESTION: What is the sensitivity and specificity of 18F-fludeoxyglucose
      positron emission tomography/computed tomography (FDG-PET/CT) imaging for
      detecting mediastinal lymph node involvement in patients with potentially
      resectable non-small cell lung cancer (NSCLC)? BOTTOM LINE: Sensitivity and
      specificity of FDG-PET/CT imaging ranged from 0.77 to 0.81 for sensitivity and
      0.79 to 0.90 for specificity, and were related to the brand of scanner, NSCLC
      subtype, FDG dose, and country of study origin. These sensitivities and
      specificities are not sufficiently accurate to warrant reliance on FDG-PET/CT
      scanning alone to make decisions about surgery as a single option for patients
      with potentially resectable NSCLC. Instead FDG-PET/CT imaging should be used to
      determine whether the next step should be biopsy (endobronchial ultrasound-guided
      biopsy or mediastinoscopy) or surgical resection.

PMID- 25871674
TI  - Screening for osteoporosis.

PMID- 25871675
TI  - Data breaches of protected health information in the United States.

PMID- 25871676
TI  - Aspirin for prevention of cardiovascular events in older Japanese patients.

PMID- 25871677
TI  - Long-term survival following bariatric surgery in the VA health system.

PMID- 25871678
TI  - Aspirin for prevention of cardiovascular events in older Japanese patients-
      reply.

PMID- 25871679
TI  - Long-term survival following bariatric surgery in the VA health system--reply.

PMID- 25871680
TI  - Racial and ethnic differences in breast cancer diagnosis and survival.

PMID- 25871682
TI  - Incorrect data in text and table.

PMID- 25871681
TI  - Racial and ethnic differences in breast cancer diagnosis and survival--reply.

PMID- 25871684
TI  - Is the physician an "easy mark"?

PMID- 25871685
TI  - JAMA patient page. Alzheimer disease.

PMID- 25871686
TI  - In memoriam: Martin A. Schulman, Ph.D., 1944-2014.

PMID- 25871687
TI  - Critical notes on the neuro-evolutionary archaeology of affective systems.
AB  - If progress is to be made in resolving the debate over the relevance of
      neuroscientific findings to psychoanalysis, a clearer distinction must be
      established between a narrow definition of psychoanalysis as "praxis" (the
      science of lived experience and its conflicts or contradictions) and a definition
      that focuses on metapsychology as objectivistic theory-building. The
      investigations of Jaak Panksepp on the "neuro-archaeology" of affective systems
      are reviewed as an example of how findings in neuroscience cannot be legitimately
      extrapolated to offer conclusions about the domain of lived experience. In this
      context, Freud's shifting standpoint is reviewed and, following the writings of
      Jean Laplanche, the significance of Freud's distinction between "drives" or
      libidinality, as acquired through experience, and "instincts," which are purely
      biological, is emphasized. It is argued that there is an unavoidable component of
      myth-making in any consideration of the connection between neural circuitry and
      the domain of psychic representations. Freud's need for a notion of drive or
      energy, which is required to understand the findings of free-associative method,
      is admittedly mythematic, but it implies a major challenge to extant
      philosophical doctrines of the "mind/body" question (emergentism, double-aspect
      monism, and neutral monism). Thus, whereas psychoanalysis as praxis is, in
      Freud's words, "free to follow its own requirements," the claims of
      metapsychology are not so unrestrained. Further debate is required on the
      irrelevance of a revised objectivistic theory of the "mental apparatus" to the
      venture of healing the fracturing of our lived experience. 

PMID- 25871688
TI  - Reply to Barratt.

PMID- 25871690
TI  - Response to Russell.

PMID- 25871691
TI  - Response to Russell.

PMID- 25871692
TI  - On "free associative activities".
AB  - Free association has been at the heart of the analytic process for decades,
      though nowadays the work with borderline and psychotic mental functioning has
      become more common. We discuss and compare contributions from the Kleinian and
      the French psychoanalytic models regarding the role of free association and the
      analyst when working with these disorders. Drawing on case material, we suggest a
      broader conceptualization of free association--free associative activities--which
      encompasses communications that cannot be expressed through verbal modes because
      of their primitiveness. Their working through in the analytic couple could allow
      a first representation of unsymbolized early psychic traumas.

PMID- 25871693
TI  - Banal no more: an essay on the film Hannah Arendt, with special reference to
      Eichmann and the Nazi killing groups.
AB  - This movie review and essay about the recent film Hannah Arendt by director
      Margarethe von Trotta seeks to examine Arendt's controversial term "banality of
      evil" as well as the nature of Arendt's misperception of Adolph Eichmann as
      thoughtless, and to situate Eichmann's personality within recent understandings
      of totalitarian group behavior and organizational killers. What emerges is that
      Arendt was unable to understand Eichmann's ruthless indifference to others as
      well as his attraction to being a Nazi and to organized mass killing. This paper
      examines Mann's (2005) formulation of different levels of functional attraction
      to totalitarian perpetrators, in which a racial morality is imposed and
      restrictions to eliminist violence are removed. Under such group conditions,
      violent "sleeper" needs emerge and are rationalized by political beliefs. In
      conclusion, the term "banality of evil" has little explanative value, while
      violent mass murder continues to this day as a totalitarian solution. 

PMID- 25871694
TI  - The trip to Bountiful: a study in family pathology in the work of Horton Foote.
AB  - This paper focusing on a major dramatic work by Horton Foote represents a
      compilation of many tragic themes he repeated over a lifetime of playwriting. The
      author pinpoints the psychological limitations of the characters and the
      problematic plot lines as they relate to Horton Foote in his own life experience.
      Psychoanalytic developmental theory is used to enlighten the reader with a
      powerful account of the playwright's struggle to fulfill his talent as well as to
      inform the public of the cultural problems underlying the life of the people and
      events of the time. 

PMID- 25871697
TI  - Stroke knowledge in Spanish-speaking populations.
AB  - BACKGROUND: Spanish is the second most-spoken language in the world. Spanish
      speaking populations (SSP) have heterogeneous cultural backgrounds, racial and
      ethnical origins, economic status, and access to health care systems. There are
      no published reviews about stroke knowledge in SSP. We reviewed the existing
      literature addressing stroke knowledge among SSP and propose here some future
      directions for research. SUMMARY: We identified 18 suitable studies by searching
      PubMed, Lilacs, Scopus, Embase, Cochrane and Scielo databases, and by looking at
      reference lists of eligible articles. We also included 2 conference abstracts.
      Data related to stroke knowledge from studies of Spanish-speakers were analyzed.
      Key Messages: Little is known about stroke knowledge in SSP, especially in Latin
      America. Information is lacking even among subjects at risk, stroke patients,
      stroke survivors, and health care providers. 'Ictus', the word used for stroke in
      Spanish, is largely unrecognized among subjects at risk. Furthermore, access to
      medical care and the availability of neurologists are suboptimal in many regions.
      There are several potential issues to solve regarding stroke knowledge and stroke
      care in SSP. Programs to educate the general population and non-neurologists
      medical providers in stroke and telemedicine may be better ways of improving the
      present situation.

PMID- 25871698
TI  - Plasmon-Enhanced Terahertz Photodetection in Graphene.
AB  - We report a large area terahertz detector utilizing a tunable plasmonic resonance
      in subwavelength graphene microribbons on SiC(0001) to increase the absorption
      efficiency. By tailoring the orientation of the graphene ribbons with respect to
      an array of subwavelength bimetallic electrodes, we achieve a condition in which
      the plasmonic mode can be efficiently excited by an incident wave polarized
      perpendicular to the electrode array, while the resulting photothermal voltage
      can be observed between the outermost electrodes. 

PMID- 25871699
TI  - Comprehensive Analysis of Serum microRNAs in Autoimmune Pancreatitis.
AB  - BACKGROUND/AIMS: Autoimmune pancreatitis (AIP) is a rare disease that has
      recently emerged as a unique type of pancreatitis with a presumed autoimmune
      etiology. MicroRNA (miRNA) is a small non-coding RNA that targets multiple mRNAs.
      miRNAs might exist in serum in a stabilized form, suggesting its potential
      application as a biomarker. We here examined the miRNA expression profile in the
      serum of patients with AIP. METHODS: miRNAs were prepared from serum samples of
      patients with various pancreatic diseases (AIP (n = 3, each before and after the
      steroid therapy), chronic pancreatitis (n = 5), pancreatic cancer (n = 5)) or
      healthy controls (n = 5). A human miRNA Oligo chip containing approximately 2,000
      miRNAs was used to identify differentially expressed miRNAs. Ingenuity Pathway
      Analysis (IPA) was used for the integrated analysis of altered miRNAs. RESULTS:
      Microarray analysis identified miRNAs highly expressed in the serum of patients
      with AIP: 13 miRNAs vs. CP, 204 miRNAs vs. pancreatic cancer, and 19 miRNAs vs.
      healthy controls. miR-150-5p was commonly upregulated in AIP compared to the
      other samples. IPA revealed the most biological processes affected by the steroid
      therapy including cellular development, cellular growth, and cell movement.
      CONCLUSION: Our results identified that miRNAs were differentially expressed in
      the serum of AIP patients.

PMID- 25871700
TI  - Understanding and reducing work-related psychological distress in interns: a
      systematic review.
AB  - The aim of this study was to collate and evaluate studies investigating either
      the factors influencing work-related psychological distress in postgraduate year
      one (PGY1) doctors or the strategies designed to reduce it. This is a systematic
      review conducted in May 2014. The data sources were key databases (MEDLINE,
      PsycINFO and Embase) and manual searches of reference lists for relevant studies
      published in the last 15 years. This study is an empirical research designed
      either to elucidate the factors influencing work-related psychological distress
      in PGY1 doctors, or examine the effects of an intervention designed to reduce it.
      Key information was extracted into an electronic data extraction form, which
      incorporated elements of Murphy's model of work stress factors. A total of 21
      studies was included in the review; 16 studies had examined the factors
      influencing work-related psychological distress, four studies had investigated
      strategies to reduce it, and a single study addressed both. Analysis of the
      findings of each individual study through the conceptual framework provided by
      Murphy's model revealed a discrepancy between the factors influencing work
      related psychological distress and the focus of strategies designed to reduce it.
      Factors such as career progression and a PGY1 doctor's role within the
      organisation were not addressed in the interventions identified. Significant
      sources of psychological distress in PGY1 doctors remain overlooked by current
      interventions. Strategies designed to prevent or reduce psychological distress
      should be broad-based and grounded in both the literature exploring salient
      factors and existing theories of work-related stress.

PMID- 25871701
TI  - Classification of primary progressive aphasia: Do unsupervised data mining
      methods support a logopenic variant?
AB  - Our objective was to test whether data mining techniques, through an unsupervised
      learning approach, support the three-group diagnostic model of primary
      progressive aphasia (PPA) versus the existence of two main/classic groups. A
      series of 155 PPA patients observed in a clinical setting and subjected to at
      least one neuropsychological/language assessment was studied. Several
      demographic, clinical and neuropsychological attributes, grouped in distinct
      sets, were introduced in unsupervised learning methods (Expectation Maximization,
      K-Means, X-Means, Hierarchical Clustering and Consensus Clustering). Results
      demonstrated that unsupervised learning methods revealed two main groups
      consistently obtained throughout all the analyses (with different algorithms and
      different set of attributes). One group included most of the agrammatic/non
      fluent and some logopenic cases while the other was mainly composed of semantic
      and logopenic cases. Clustering the patients in a larger number of groups (k > 2)
      revealed some clusters composed mostly of non-fluent or of semantic cases.
      However, we could not evidence any group chiefly composed of logopenic cases. In
      conclusion, unsupervised data mining approaches do not support a clear
      distinction of logopenic PPA as a separate variant. 

PMID- 25871703
TI  - New reagent for highly efficient synthesis of trifluoromethyl-substituted arenes
      and heteroarenes.
AB  - A new reagent trimethylsilyl chlorodifluoroacetate (TCDA) is reported for the
      introduction of a -CF3 group to arenes and heteroarenes. Compared with current
      known reagents, TCDA shows very broad scope with respect to electron-deficient, 
      neutral, and -rich aryl/heteroaryl iodides as well as excellent functional group
      tolerance, including ester, amide, aldehyde, hydroxyl, and carboxylic acid. 

PMID- 25871702
TI  - A Quality Improvement Intervention to Reduce Indwelling Tunneled Pleural Catheter
      Infection Rates.
AB  - RATIONALE: The indwelling tunneled pleural catheter has altered the management of
      patients with dyspnea related to malignant pleural effusions. However, indwelling
      tunneled pleural catheter placement does not remain free from risk. The most
      commonly reported risk is infection. OBJECTIVES: The aim of this paper is to
      describe our continuous quality improvement program for infection rate
      recognition, the process changes implemented for improvement, and subsequent
      outcomes. METHODS: All patients undergoing indwelling tunneled pleural catheter
      placement at The Johns Hopkins Medical Institutions between May 2009 and April
      2014 were identified. The primary outcome was the incidence of infection within
      the preintervention and intervention cohorts. Intervention was identified as use
      of preoperative antibiotics, full sterile draping, and limiting placement to a
      single defined location. MEASUREMENTS AND MAIN RESULTS: A total of 225 indwelling
      tunneled pleural catheter placements were performed in 201 patients during the
      study period, and the overall infection rate was 5.8%. During the preintervention
      period, 134 placements were performed, and 91 placements occurred during the
      intervention period. A preintervention infection rate was identified as 8.2%,
      with a significant decrease to 2.2% (P = 0.049) within the intervention cohort.
      CONCLUSIONS: The use of a continuous quality improvement program to review
      indwelling tunneled pleural catheter practices can result in the identification
      of infectious complications and lead to implementation of measures to improve
      patient outcomes.

PMID- 25871704
TI  - It's never as easy as ABC: Understandings of AIDS in Botswana1.
AB  - This paper argues for the importance of examining the way the messages of
      Government AIDS educational campaigns in Africa are interpreted at the local
      level. One of the striking features of the HIV/AIDS epidemic in Botswana is that
      it is not universally seen as a 'new' disease syndrome but as an 'old' one.
      HIV/AIDS has been interpreted by traditional healers as a manifestation of old
      'Tswana' diseases, acquiring new virulence because of the increasing disrespect
      for the mores of traditional culture, or as a result of 'old' diseases mutating
      as they have 'mixed together'. This alternative discourse of AIDS is set first in
      the context of official Health Education programmes and policy. It is argued that
      the fact that these programmes and policies have been couched exclusively in
      biomedical terms, and in apparent ignorance of other conceptualisations, has been
      detrimental to public education and understanding. Further, it has encouraged the
      development of a powerful and coherent counter discourse, based in the common
      understandings of Tswana society and cosmology. The main concern of this paper is
      to contextualise this counter discourse in order to understand why there has been
      a move to 'claim' the disease, turning it thus from a global problem into a local
      one. It is argued that it allows not only for a trenchant critique of current
      morality but also of the Government and the west. In turn, this raises a more
      general policy dilemma with regard to the dissemination of medical information in
      societies with plural health care systems, each operating on the basis of
      different truth claims. Where, as in southern Africa, these coincide with
      entrenched social divisions, educational interventions carry an inevitable
      political load, operating to locate the Government and its spokespeople on one or
      other side of the social (and epistemological) divide. 

PMID- 25871705
TI  - The correlates of safe sex practices among Rwandan youth: a positive deviance
      approach.
AB  - This paper presents the results of a 2001 sample survey and uses an ideation
      model to identify the factors affecting primary sexual abstinence and condom use
      among Rwandan youth. The findings showed that urban residence and age negatively
      influence primary sexual abstinence and positively affect condom use. Living
      within the same household as the father tends to protect girls from early sexual
      experimentation but has no noticeable effect on boys. Moslems are considerably
      less likely than Christians to report primary sexual abstinence. The use of
      alcohol tends to be negatively associated with sexual abstinence. The ideational
      factors that are significant for primary sexual abstinence are perceptions about
      the sexual behaviours of peers, perceived self-efficacy to refuse sex with
      someone truly loved, perceived self-efficacy to refuse sex with someone known for
      more than three months, self-esteem and attitudes toward premarital sex. As for
      condom use, the ideational variables with significant independent effects on the
      behavior are: discussion of HIV/AIDS with sexual partner, and to a lesser extent,
      the perceived self-efficacy to use condoms, and discussion of condom use with the
      sex partner. The programmatic and policy implications of the results are
      discussed. 

PMID- 25871706
TI  - Kissing the cobra: Sexuality and high risk in a generalised epidemic-a case study
      of White university students.
AB  - This paper explores the social factors that may account for the way the HIV-AIDS
      epidemic is unfolding in a racially segmented and socially differentiated
      society. As a sexually transmitted infectious disease that particularly infects
      adolescents and decimates young adults, there is an urgent need to critically
      assess assumptions about the influence of culture and social relations on
      differences in patterns and the scale of infection across racial groups in South
      Africa. The point of departure is the recognition that while nationally there is
      a generalised epidemic of gigantic proportions, the epidemic among young White
      adults is still nascent. Through a qualitative exploration of White student
      perceptions of risk, sexual networking and practices in an HIV-AIDS environment,
      this small study hopes to shed light on some of the social and cultural issues
      surrounding the epidemic. 

PMID- 25871707
TI  - Evidence of AIDS mortality from an alternative source: A Swaziland case study.
AB  - This paper explores a way of measuring AIDS mortality in the absence of vital
      registration. It looks at the death notices in the major daily newspaper in
      Swaziland, The Times of Swaziland, and asks if these can be analysed to give a
      picture of changing mortality. It shows how clear trends can be discerned. 

PMID- 25871708
TI  - 'Before we were sleeping, now we are awake': Preliminary evaluation of the
      Stepping Stones sexual health programme in The Gambia.
AB  - Community-based behavioural interventions aimed at reducing risky sexual
      behaviour have yet to be shown to be effective in the developing world. Stepping
      Stones is a participatory STI/HIV prevention workshop programme based on
      empowerment techniques, which has been adapted to an infertility prevention
      framework for The Gambia. This paper describes a preliminary evaluation in two
      villages where the intervention was carried out compared to two control villages.
      Methods used include: participatory evaluation; 84 in-depth interviews; seven
      focus group discussions; a knowledge, attitudes and practice questionnaire
      administered to a random sample of 25% of the adult population at three time
      points; and monitoring of condom supply. The structure of the evaluation is based
      on the themes derived from the qualitative data. The infertility prevention
      approach made it possible to overcome resistance to discussing the topics of
      sexual and reproductive health. An atmosphere of trust was created and men were
      persuaded to participate in the programme as they felt that their own needs were
      being addressed. Participants enjoyed the programme and found the content
      relevant. Knowledge of the modes of transmission of HIV and sexually transmitted
      infections and levels of risk awareness increased. The value of condoms in
      particular situations was recognised: for sex before marriage, within marriage
      (when the woman is breastfeeding) and with non-marital partners. Women reported
      that they would insist on condom use outside marriage and even ask their husbands
      to use condoms for non-marital sex. Condom monitoring data suggested that condom
      uptake had increased. It was reported that there was significant increase in
      dialogue within marriage with the consequence that there were fewer disagreements
      and incidents of domestic violence. Diffusion of the messages of Stepping Stones
      appeared to have taken place with non-participants including children. The
      evaluation techniques used can now be refined in order to generate further
      evidence on a larger scale and over a longer period. 

PMID- 25871709
TI  - Necessity and sufficiency in the aetiology of HIV/AIDS: The science, history and
      politics of the causal link.
AB  - An earlier version of this paper was presented at the AIDS in Context Conference,
      University of the Witwatersrand, Johannesburg, 4-7 April 2001 Public debates on
      HIV/AIDS in South Africa have, for the last three years, been dominated by the
      controversy around the causal link between HIV and AIDS. A decision on this
      question has direct consequences for health policy, treatment, and education.
      However, this question also warrants a medical-historical investigation into
      concepts and models of causality and the way they have panned out in medical
      scientific revolutions, and in diagnostics and treatment. As this paper attempts
      to show, necessary and sufficient criteria for disease causation are crucial in
      the debates on the aetiology of HIV/AIDS. In the course of the history of medical
      diagnostics, the sufficiency criterion has been considerably modified, while the
      necessity criterion has been foregrounded. It has been shown that the
      difficulties surrounding the establishment of strict sufficiency criteria do not
      preclude the elaboration of an aetiology of HIV/AIDS. While mainstream medical
      science privileges the necessity criterion, the AIDS dissenters insist on strict
      sufficiency for conclusive proof of the causal link between HIV and AIDS. This
      paper aims to show that both criteria have a role to play, but in differentiated
      ways and at different and distinct sites of intervention. 

PMID- 25871710
TI  - Embodied history. Uniqueness and exemplarity of South African AIDS.
AB  - The exceptionality of AIDS in South Africa, both for its epidemiological features
      and public controversies, seems to have its correspondence in the exceptionalism
      of South African history, with its unprecedented regime of apartheid and its
      unexpected turn to democracy. The article shows that AIDS in this country can
      simultaneously be seen as unique (because of the historical context in which it
      is inscribed) and exemplar (of social determinants observed in other countries
      characterised by similar past or present of domination). As an alternative to
      cultural and behavioural models of the epidemic which have been widely spread on
      the African continent, the concept of embodiment of history is proposed in order
      to account for both the structural facts underlying the epidemic (inequality,
      violence, migration) and the construction of collective as well as individual
      narratives of the disease (including victimisation and accusation). 

PMID- 25871711
TI  - HIV/AIDS policies, practices and conditions in South African prisons: Criticisms
      and alternatives. Towards a research agenda.
AB  - The level of HIV infection in South African prisoners is unknown. However, given
      that 4.2 million citizens or 20% of the adult population are infected by HIV then
      the problem of infection within the prison system would seem to be a large and a
      significant management issue. Policies to treat HIV+ prisoners and prevent HIV
      transmission have been developed. However, the efficacy of those programmes
      implemented to prevent HIV transmission is questionable. The reasons for this
      situation include lack of resources like condoms, lubricant, disinfectants and
      availability of testing. Prison conditions also militate against success
      especially overcrowding, poor health care and nutrition. Little research has been
      undertaken into HIV within the prison system and the lack of transparency in
      management of the system is a major hindrance in achieving better public policy
      outcomes. The issues of importance to policy research on HIV/AIDS in prison,
      which should receive early attention, include: 1) Prevalence rate determination;
      2) Treatment of HIV+ prisoners; 3) Education programmes; and 4) Early release
      policy and practices. 

PMID- 25871712
TI  - HIV/AIDS: South African women at risk.
AB  - A previous version of this paper was presented at the AIDS in Context Conference,
      University of the Witwatersrand, Johannesburg, 4-7 April 2001 This paper engages
      some aspects of the HIV/AIDS epidemic and the complexities associated with it. It
      outlines the socio-epidemiological patterns of the epidemic and in doing so
      identifies the groups with the greatest and fastest growing rates of infection.
      The pattern of the epidemic in South Africa is as follows: it is primarily a
      heterosexual one, the rates of infection in the general population are very high,
      and the percentage of HIV positive women is greater than men. An additional
      feature is the young age of onset of infection for women. These data demonstrate
      the need to focus our attention on young African women and the factors
      underpinning their predicament. In order to shed light on the position of women
      in the epidemic and the particular risks they face, we examine the long-standing
      relationship between gender and racial inequalities and health. Within the
      constraints of limited and flawed statistical data, the paper argues that a
      complex interaction of material, social, cultural and behavioural factors shape
      the nature, process and outcome of the epidemic in South Africa. It concludes
      with recommendations for the way forward. 

PMID- 25871713
TI  - Does dopamine mediate salt-dependent urinary renalase secretion in man?

PMID- 25871714
TI  - Research on joint parameter inversion for an integrated underground displacement
      3D measuring sensor.
AB  - Underground displacement monitoring is a key means to monitor and evaluate
      geological disasters and geotechnical projects. There exist few practical
      instruments able to monitor subsurface horizontal and vertical displacements
      simultaneously due to monitoring invisibility and complexity. A novel underground
      displacement 3D measuring sensor had been proposed in our previous studies, and
      great efforts have been taken in the basic theoretical research of underground
      displacement sensing and measuring characteristics by virtue of modeling,
      simulation and experiments. This paper presents an innovative underground
      displacement joint inversion method by mixing a specific forward modeling
      approach with an approximate optimization inversion procedure. It can realize a
      joint inversion of underground horizontal displacement and vertical displacement
      for the proposed 3D sensor. Comparative studies have been conducted between the
      measured and inversed parameters of underground horizontal and vertical
      displacements under a variety of experimental and inverse conditions. The results
      showed that when experimentally measured horizontal displacements and vertical
      displacements are both varied within 0~30 mm, horizontal displacement and
      vertical displacement inversion discrepancies are generally less than 3 mm and 1
      mm, respectively, under three kinds of simulated underground displacement
      monitoring circumstances. This implies that our proposed underground displacement
      joint inversion method is robust and efficient to predict the measuring values of
      underground horizontal and vertical displacements for the proposed sensor.

PMID- 25871716
TI  - Bridge displacement monitoring method based on laser projection-sensing
      technology.
AB  - Bridge displacement is the most basic evaluation index of the health status of a
      bridge structure. The existing measurement methods for bridge displacement
      basically fail to realize long-term and real-time dynamic monitoring of bridge
      structures, because of the low degree of automation and the insufficient
      precision, causing bottlenecks and restriction. To solve this problem, we
      proposed a bridge displacement monitoring system based on laser projection
      sensing technology. First, the laser spot recognition method was studied. Second,
      the software for the displacement monitoring system was developed. Finally, a
      series of experiments using this system were conducted, and the results show that
      such a system has high measurement accuracy and speed. We aim to develop a low
      cost, high-accuracy and long-term monitoring method for bridge displacement based
      on these preliminary efforts. 

PMID- 25871715
TI  - A wireless and portable electronic nose to differentiate musts of different
      ripeness degree and grape varieties.
AB  - Two novel applications using a portable and wireless sensor system (e-nose) for
      the wine producing industry-The recognition and classification of musts coming
      from different grape ripening times and from different grape varieties-Are
      reported in this paper. These applications are very interesting because a lot of
      varieties of grapes produce musts with low and similar aromatic intensities so
      they are very difficult to distinguish using a sensory panel. Therefore the
      system could be used to monitor the ripening evolution of the different types of
      grapes and to assess some useful characteristics, such as the identification of
      the grape variety origin and to prediction of the wine quality. Ripening grade of
      collected samples have been also evaluated by classical analytical techniques,
      measuring physicochemical parameters, such as, pH, Brix, Total Acidity (TA) and
      Probable Grade Alcoholic (PGA). The measurements were carried out for two
      different harvests, using different red (Barbera, Petit Verdot, Tempranillo, and
      Touriga) and white (Malvar, Malvasia, Chenin Blanc, and Sauvignon Blanc) grape
      musts coming from the experimental cellar of the IMIDRA at Madrid. Principal
      Component Analysis (PCA) and Probabilistic Neural Networks (PNN) have been used
      to analyse the obtained data by e-nose. In addition, and the Canonical
      Correlation Analysis (CCA) method has been carried out to correlate the results
      obtained by both technologies. 

PMID- 25871717
TI  - Detection of atmospheric water deposits in porous media using the TDR technique.
AB  - Investigating the intensity of atmospheric water deposition and its diurnal
      distribution is essential from the ecological perspective, especially regarding
      dry geographic regions. It is also important in the context of monitoring the
      amount of moisture present within building materials in order to protect them
      from excessive humidity. The objective of this study was to test a constructed
      sensor and determine whether it could detect and track changes in the intensity
      of atmospheric water deposition. An operating principle of the device is based on
      the time-domain reflectometry technique. Two sensors of different plate volumes
      were manufactured. They were calibrated at several temperatures and tested during
      field measurements. The calibration turned out to be temperature independent. The
      outdoor measurements indicated that the upper limits of the measurement ranges of
      the sensors depended on the volumes of the plates and were equal to 1:2 and 2:8
      mm H2O. The respective sensitivities were equal to 3.2 x 10(-3) and 7.5 x 10(-3)
      g?ps(-1). The conducted experiments showed that the construction of the designed
      device and the time-domain reflectometry technique were appropriate for detecting
      and tracing the dynamics of atmospheric water deposition. The obtained outcomes
      were also collated with the readings taken in an actual soil sample. For this
      purpose, an open container sensor, which allows investigating atmospheric water
      deposition in soil, was manufactured. It turned out that the readings taken by
      the porous ceramic plate sensor reflected the outcomes of the measurements
      performed in a soil sample.

PMID- 25871718
TI  - Noninvasive and real-time plasmon waveguide resonance thermometry.
AB  - In this paper, the noninvasive and real-time plasmon waveguide resonance (PWR)
      thermometry is reported theoretically and demonstrated experimentally. Owing to
      the enhanced evanescent field and thermal shield effect of its dielectric layer,
      a PWR thermometer permits accurate temperature sensing and has a wide dynamic
      range. A temperature measurement sensitivity of 9.4 * 10(-3)  degrees C is
      achieved and the thermo optic coefficient nonlinearity is measured in the
      experiment. The measurement of water cooling processes distributed in one
      dimension reveals that a PWR thermometer allows real-time temperature sensing and
      has potential to be applied for thermal gradient analysis. Apart from this, the
      PWR thermometer has the advantages of low cost and simple structure, since our
      transduction scheme can be constructed with conventional optical components and
      commercial coating techniques.

PMID- 25871719
TI  - Monitoring of low levels of furfural in power transformer oil with a sensor
      system based on a POF-MIP platform.
AB  - In this work an innovative, miniaturized and low cost optical chemical sensor
      (POF-MIP platform), based on a molecular imprinted polymer (MIP) and surface
      plasmon resonance in a plastic optical fiber (POF), is presented and
      preliminarily tested for monitoring of furfural (furan-2-carbaldehyde) in
      transformer oil. To this end, the optical platform was coupled to an MIP layer,
      highly selective for furfural. The ability of the developed sensor to directly
      detect furfural in the insulating oil was investigated. The detection limit of
      the sensor has been found to be 9 ppb, with a linear response up to about 30 ppb.
      However there is a sensible response up to 0.15 ppm. Because of the small
      linearity range, the Hill equation is suggested for the quantification. The
      sensor has been effectively tested in real oil samples collected from aged
      electrical equipment removed from service. The assessed concentration of furfural
      is in good agreement with that evaluated by a high pressure liquid chromatography
      (HLPC) method, confirming the good selectivity of the proposed sensor. 

PMID- 25871720
TI  - Development and beam-shape analysis of an integrated fiber-optic confocal probe
      for high-precision central thickness measurement of small-radius lenses.
AB  - This work describes a new design of a fiber-optic confocal probe suitable for
      measuring the central thicknesses of small-radius optical lenses or similar
      objects. The proposed confocal probe utilizes an integrated camera that functions
      as a shape-encoded position-sensing device. The confocal signal for thickness
      measurement and beam-shape data for off-axis measurement can be simultaneously
      acquired using the proposed probe. Placing the probe's focal point off-center
      relative to a sample's vertex produces a non-circular image at the camera's image
      plane that closely resembles an ellipse for small displacements. We were able to
      precisely position the confocal probe's focal point relative to the vertex point
      of a ball lens with a radius of 2.5 mm, with a lateral resolution of 1.2 um. The
      reflected beam shape based on partial blocking by an aperture was analyzed and
      verified experimentally. The proposed confocal probe offers a low-cost, high
      precision technique, an alternative to a high-cost three-dimensional surface
      profiler, for tight quality control of small optical lenses during the
      manufacturing process. 

PMID- 25871721
TI  - Measurement method of magnetic field for the wire suspended micro-pendulum
      accelerometer.
AB  - Force producer is one of the core components of a Wire Suspended Micro-Pendulum
      Accelerometer; and the stability of permanent magnet in the force producer
      determines the consistency of the acceleration sensor's scale factor. For an
      assembled accelerometer; direct measurement of magnetic field strength is not a
      feasible option; as the magnetometer probe cannot be laid inside the micro-space
      of the sensor. This paper proposed an indirect measurement method of the remnant
      magnetization of Micro-Pendulum Accelerometer. The measurement is based on the
      working principle of the accelerometer; using the current output at several
      different scenarios to resolve the remnant magnetization of the permanent magnet.
      Iterative Least Squares algorithm was used for the adjustment of the data due to
      nonlinearity of this problem. The calculated remnant magnetization was 1.035 T.
      Compared to the true value; the error was less than 0.001 T. The proposed method
      provides an effective theoretical guidance for measuring the magnetic field of
      the Wire Suspended Micro-Pendulum Accelerometer; correcting the scale factor and
      temperature influence coefficients; etc. 

PMID- 25871722
TI  - A label-free immunosensor for ultrasensitive detection of ketamine based on
      quartz crystal microbalance.
AB  - In this study, we have developed a label-free immunosensor with the variation of
      resonance frequency (Deltaf) of a quartz crystal microbalance (QCM) as readout
      signal for ultrasensitive detection of Ketamine (KT). An optimized strategy for
      immobilization of KT antibody on the surface of the QCM chip was implemented via
      the self-assembly modification of 3-mercaptopropionic acid, and then activated
      with 1-ethyl-3-(3-dimethylaminoprophl) carbodiimide and n-hydroxysuccinimide. The
      specific affinity between the antibody and the antigen ensured a selective
      response toward KT. The Deltaf linearly related to the concentration of KT in the
      range of 1 to 40 pg/mL, with a detection limit of 0.86 pg/mL (S/N = 3). The
      obtained immunosensor was applied to detect the KT in spiked human urine without
      any pretreatment but dilution with recoveries from 91.8% to 108%. The developed
      sensor is promising to perform the portable or on-spot KT detection in clinic or
      forensic cases.

PMID- 25871723
TI  - EEMD independent extraction for mixing features of rotating machinery
      reconstructed in phase space.
AB  - Empirical Mode Decomposition (EMD), due to its adaptive decomposition property
      for the non-linear and non-stationary signals, has been widely used in vibration
      analyses for rotating machinery. However, EMD suffers from mode mixing, which is
      difficult to extract features independently. Although the improved EMD, well
      known as the ensemble EMD (EEMD), has been proposed, mode mixing is alleviated
      only to a certain degree. Moreover, EEMD needs to determine the amplitude of
      added noise. In this paper, we propose Phase Space Ensemble Empirical Mode
      Decomposition (PSEEMD) integrating Phase Space Reconstruction (PSR) and Manifold
      Learning (ML) for modifying EEMD. We also provide the principle and detailed
      procedure of PSEEMD, and the analyses on a simulation signal and an actual
      vibration signal derived from a rubbing rotor are performed. The results show
      that PSEEMD is more efficient and convenient than EEMD in extracting the mixing
      features from the investigated signal and in optimizing the amplitude of the
      necessary added noise. Additionally PSEEMD can extract the weak features
      interfered with a certain amount of noise. 

PMID- 25871724
TI  - Pedestrian detection in far-infrared daytime images using a hierarchical codebook
      of SURF.
AB  - One of the main challenges in intelligent vehicles concerns pedestrian detection
      for driving assistance. Recent experiments have showed that state-of-the-art
      descriptors provide better performances on the far-infrared (FIR) spectrum than
      on the visible one, even in daytime conditions, for pedestrian classification. In
      this paper, we propose a pedestrian detector with on-board FIR camera. Our main
      contribution is the exploitation of the specific characteristics of FIR images to
      design a fast, scale-invariant and robust pedestrian detector. Our system
      consists of three modules, each based on speeded-up robust feature (SURF)
      matching. The first module allows generating regions-of-interest (ROI), since in
      FIR images of the pedestrian shapes may vary in large scales, but heads appear
      usually as light regions. ROI are detected with a high recall rate with the
      hierarchical codebook of SURF features located in head regions. The second module
      consists of pedestrian full-body classification by using SVM. This module allows
      one to enhance the precision with low computational cost. In the third module, we
      combine the mean shift algorithm with inter-frame scale-invariant SURF feature
      tracking to enhance the robustness of our system. The experimental evaluation
      shows that our system outperforms, in the FIR domain, the state-of-the-art Haar
      like Adaboost-cascade, histogram of oriented gradients (HOG)/linear SVM (linSVM)
      and MultiFtrpedestrian detectors, trained on the FIR images. 

PMID- 25871725
TI  - Simultaneous imaging of two different cancer biomarkers using aptamer-conjugated
      quantum dots.
AB  - Studying gene expression profile in a single cancer cell is important because
      multiple genes are associated with cancer development. Quantum dots (QDs) have
      been utilized as biological probes for imaging and detection. QDs display
      specific optical and electrical properties that depend on their size that can be
      applied for imaging and sensing applications. In this study, simultaneous imaging
      of the cancer biomarkers, tenascin-C and nucleolin, was performed using two types
      of aptamer-conjugated QDs. The simultaneous imaging of these two different cancer
      markers in three cancer cell lines was reliable and cell line-specific. Current
      requirements for cancer imaging technologies include the need for simple
      preparation methods and the ability to detect multiple cancer biomarkers and
      evaluate their intracellular localizations. The method employed in this study is
      a feasible solution to these requirements. 

PMID- 25871726
TI  - Temperate Drosophila preserve cardiac function at low temperature.
AB  - Most insects are chill susceptible and will enter a coma if exposed to
      sufficiently low temperature. This chill coma has been associated with a failure
      of the neuromuscular system. Insect heart rate (HR) is determined by intrinsic
      regulation (muscle pacemaker) with extrinsic (nervous and humoral) input. By
      examining the continually active heart of five Drosophila species with markedly
      different cold tolerance, we investigated whether cardiac performance is related
      to the whole animal critical thermal minimum (CTmin). Further, to separate the
      effects of cold on extrinsic and intrinsic regulators of HR, we measured HR under
      similar conditions in decapitated flies as well as amputated abdomens of
      Drosophila montana. Cardiac performance was assessed from break points in HR
      temperature relationship (Arrhenius break point, ABP) and from the HR cessation
      temperature. Among the five species, we found strong relationships for both the
      HR-ABP and HR cessation temperatures to whole animal CTmin, such that temperate
      Drosophila species maintained cardiac function at considerably lower temperatures
      than their tropical congeners. Hearts of amputated abdomens, with reduced
      extrinsic input, had a higher thermal sensitivity and a significantly lower break
      point temperature, suggesting that central neuronal input is important for
      stimulating HR at low temperatures. 

PMID- 25871727
TI  - Trajectories of multimorbidity and impacts on successful aging.
AB  - Elderly people usually have multiple chronic diseases concurrently. However,
      studies of multimorbidity patterns over long time periods are scarce. The purpose
      of this study was to examine the joint trajectories of chronic multimorbidity
      among the Taiwanese elderly and to examine related factors and to predict later
      successful aging outcomes. The data used in this study were from a nation
      representative panel survey conducted in Taiwan from 1993 to 2007. Those who
      participated in at least three waves of the survey were included in the analysis
      (in total 2584 persons and 57,012 observations). The chronic diseases included
      cardiovascular disease (CVD), chronic non-specific lung disease (CNSLD),
      arthritis, cancer, gastrointestinal disease (GI), and kidney disease. The
      multiple group-based trajectories analysis approach was applied to identify the
      trajectory groups. Four trajectory groups of multimorbidity were identified: low
      risk (55.51%), CVD risk only (15.55%), GI & CNSLD risk (20.20%), and multiple
      risks (8.74%). Related factors included age, level of education, physical
      functioning, depressive symptoms, and undergoing health examinations. The
      multimorbidity trajectories affected later physical functioning, depressive
      symptoms, cognitive function, and life satisfaction. Multiple trajectories of
      multimorbidity show the patterns of health burden and risks to successful aging
      among the elderly over time. 

PMID- 25871728
TI  - Biomechanical predictors of maximal balance recovery performance amongst
      community-dwelling older adults.
AB  - Falls are prevalent in older adults and are predicted by the maximum forward lean
      magnitude (MRLM) that can be recovered using a single step. The purpose of this
      study was to determine the relative contribution of selected neuromuscular and
      biomechanical variables associated with balance recovery to the MRLM. Forward
      loss of balance was induced by releasing participants (n=117 community-dwelling
      older adults) from a static forward lean angle. Participants were instructed to
      attempt to recover balance by taking a single step. A scalable anatomical model
      consisting of 36 degrees-of-freedom was used to compute kinematics and joint
      moments from motion capture and force plate data. Isometric muscle strength at
      the ankle, knee and hip joints was assessed using a dynamometer. A univariate
      analysis revealed that lower limb strength measures, step recovery kinematics,
      and stepping limb kinetics accounted for between 8 and 19%, 3 and 59%, and 3 and
      61% of the variance in MRLM respectively. When all variables were entered into a
      stepwise multiple regression analysis, normalised step length, peak hip extension
      moment, trunk angle at foot contact, and peak hip flexion power during stepping
      together accounted for 69% of the variance in MRLM. These findings confirm that
      successful recovery from forward loss of balance is a whole body control task
      that requires adequate trunk control and generation of adequate lower limb
      moments and powers to generate a long and rapid step. Training programmes that
      specifically target these measures may be effective in improving balance recovery
      performance and thereby contribute to fall prevention amongst older adults. 

PMID- 25871729
TI  - Deficiency of metallothionein-1 and -2 genes shortens the lifespan of the 129/Sv
      mouse strain.
AB  - Metallothionein (MT) family proteins are small molecular weight and cysteine-rich
      proteins that regulate zinc homeostasis and have potential protective effects
      against oxidative stress and toxic metals. To investigate whether MTs play a role
      in longevity determination in mammals, we measured the lifespans of wild-type
      (WT) and MT-1 and -2 gene knockout (MTKO) mice in a 129/Sv genetic background.
      MTKO mice of both sexes had shorter lifespans than WT mice. In particular, male
      MTKO mice living beyond the mean lifespan exhibited signs of weight loss,
      hunchbacked spines, lackluster fur and an absence of vigor. These results suggest
      that lifespan is shortened due to accelerated senescence in the absence of MT
      genes. 

PMID- 25871731
TI  - Detection of Y chromosome material in a 46,XX male with SRY translocation: novel
      application of cell-free fetal DNA testing.

PMID- 25871730
TI  - Integration of systems glycobiology with bioinformatics toolboxes,
      glycoinformatics resources, and glycoproteomics data.
AB  - The glycome constitutes the entire complement of free carbohydrates and
      glycoconjugates expressed on whole cells or tissues. 'Systems Glycobiology' is an
      emerging discipline that aims to quantitatively describe and analyse the glycome.
      Here, instead of developing a detailed understanding of single biochemical
      processes, a combination of computational and experimental tools are used to seek
      an integrated or 'systems-level' view. This can explain how multiple biochemical
      reactions and transport processes interact with each other to control glycome
      biosynthesis and function. Computational methods in this field commonly build in
      silico reaction network models to describe experimental data derived from
      structural studies that measure cell-surface glycan distribution. While
      considerable progress has been made, several challenges remain due to the complex
      and heterogeneous nature of this post-translational modification. First, for the
      in silico models to be standardized and shared among laboratories, it is
      necessary to integrate glycan structure information and glycosylation-related
      enzyme definitions into the mathematical models. Second, as glycoinformatics
      resources grow, it would be attractive to utilize 'Big Data' stored in these
      repositories for model construction and validation. Third, while the technology
      for profiling the glycome at the whole-cell level has been standardized, there is
      a need to integrate mass spectrometry derived site-specific glycosylation data
      into the models. The current review discusses progress that is being made to
      resolve the above bottlenecks. The focus is on how computational models can
      bridge the gap between 'data' generated in wet-laboratory studies with
      'knowledge' that can enhance our understanding of the glycome.

PMID- 25871732
TI  - Solution growth of single crystal methylammonium lead halide perovskite
      nanostructures for optoelectronic and photovoltaic applications.
AB  - Understanding crystal growth and improving material quality is important for
      improving semiconductors for electronic, optoelectronic, and photovoltaic
      applications. Amidst the surging interest in solar cells based on hybrid organic
      inorganic lead halide perovskites and the exciting progress in device
      performance, improved understanding and better control of the crystal growth of
      these perovskites could further boost their optoelectronic and photovoltaic
      performance. Here, we report new insights on the crystal growth of the perovskite
      materials, especially crystalline nanostructures. Specifically, single crystal
      nanowires, nanorods, and nanoplates of methylammonium lead halide perovskites
      (CH3NH3PbI3 and CH3NH3PbBr3) are successfully grown via a dissolution
      recrystallization pathway in a solution synthesis from lead iodide (or lead
      acetate) films coated on substrates. These single crystal nanostructures display
      strong room-temperature photoluminescence and long carrier lifetime. We also
      report that a solid-liquid interfacial conversion reaction can create a highly
      crystalline, nanostructured MAPbI3 film with micrometer grain size and high
      surface coverage that enables photovoltaic devices with a power conversion
      efficiency of 10.6%. These results suggest that single-crystal perovskite
      nanostructures provide improved photophysical properties that are important for
      fundamental studies and future applications in nanoscale optoelectronic and
      photonic devices. 

PMID- 25871733
TI  - The Impact of Different Diagnostic Criteria on the Prevalence of Sarcopenia in
      Healthy Elderly Participants and Geriatric Outpatients.
AB  - BACKGROUND: A consensus on the diagnostic criteria for sarcopenia, a common
      syndrome in the elderly, has not been reached yet. Prevalence rates vary between
      studies due to the use of different criteria encompassing different measures,
      correction factors and cutoff points. OBJECTIVE: This study compared prevalence
      rates of sarcopenia using nine sets of diagnostic criteria applied in two
      different elderly populations. METHODS: The study population encompassed 308
      healthy elderly participants (152 males, 156 females; mean age 74 years) and 123
      geriatric outpatients (54 males, 69 females; mean age 81 years). Diagnostic
      criteria included relative muscle mass, absolute muscle mass, muscle strength and
      physical performance. RESULTS: Prevalence rates of sarcopenia varied between 0
      and 15% in healthy elderly participants and between 2 and 34% in geriatric
      outpatients. CONCLUSION: This study clearly demonstrates the dependency of
      sarcopenia prevalence rates on the applied diagnostic criteria.

PMID- 25871734
TI  - Lazaroids U83836E and U74389G are potent, time-dependent inhibitors of caspase-1.
AB  - Caspase-1 is involved in inflammatory processes and is overactive in autoimmunity
      and autoinflammation. Antioxidant small molecules also play a role in the immune
      response by decreasing inflammation. An 84-membered library of pro- and
      antioxidant small molecules was screened for potential inhibitors of caspase-1.
      Thirteen compounds were discovered to reduce the activity of caspase-1 below 30%.
      The most potent inhibitors were lazaroid antioxidant molecules, U83836E (B8) and
      U74389G (B9), displaying apparent Ki values of 48.0 and 50.0 nm, respectively.
      Both demonstrated a time-dependent and reversible inhibition. 

PMID- 25871735
TI  - Acute doxorubicin-induced cardiotoxicity is associated with matrix
      metalloproteinase-2 alterations in rats.
AB  - BACKGROUND: Doxorubicin can cause cardiotoxicity. Matrix metalloproteinases (MMP)
      are responsible for degrading extracellular matrix components which play a role
      in ventricular dilation. Increased MMP activity occurs after chronic doxorubicin
      treatment. In this study we evaluated in vivo and in vitro cardiac function in
      rats with acute doxorubicin treatment, and examined myocardial MMP and
      inflammatory activation, and gene expression of proteins involved in myocyte
      calcium transients. METHODS: Wistar rats were injected with doxorubicin (Doxo, 20
      mg/kg) or saline (Control). Echocardiogram was performed 48 h after treatment.
      Myocardial function was assessed in vitro in Langendorff preparation. RESULTS: In
      left ventricle, doxorubicin impaired fractional shortening (Control 0.59 +/-
      0.07; Doxo 0.51 +/- 0.05; p < 0.001), and increased isovolumetric relaxation time
      (Control 20.3 +/- 4.3; Doxo 24.7 +/- 4.2 ms; p = 0.007) and myocardial passive
      stiffness. MMP-2 activity, evaluated by zymography, was increased in Doxo
      (Control 141338 +/- 8924; Doxo 188874 +/- 7652 arbitrary units; p < 0.001). There
      were no changes in TNF-alpha, INF-gamma, IL-10, and ICAM-1 myocardial levels.
      Expression of phospholamban, Serca-2a, and ryanodine receptor did not differ
      between groups. CONCLUSION: Acute doxorubicin administration induces in vivo left
      ventricular dysfunction and in vitro increased myocardial passive stiffness in
      rats. Cardiac dysfunction is related to myocardial MMP-2 activation. Increased
      inflammatory stimulation or changed expression of the proteins involved in
      intracellular calcium transients is not involved in acute cardiac dysfunction.

PMID- 25871736
TI  - Positive Direct Immunofluorescence Is of Better Value than ELISA-BP180 and ELISA
      BP230 Values for the Prediction of Relapse after Treatment Cessation in Bullous
      Pemphigoid: A Retrospective Study of 97 Patients.
AB  - BACKGROUND: ELISA-BP180 values and direct immunofluorescence (DIF) are prognostic
      factors for relapse after treatment cessation in bullous pemphigoid (BP).
      OBJECTIVE: To determine the relevance of ELISA-BP230 antibodies for predicting
      relapse 6 months after treatment cessation. METHODS: We retrospectively selected
      patients with BP and available data from ELISA-BP180 and -BP230 and DIF performed
      at treatment cessation. The rate of relapse was calculated at 6 months. We
      compared ELISA-BP180 and -BP230 values and DIF in patients with relapse and
      remission. RESULTS: We included 97 patients. At 6 months, 25.6% of patients
      showed relapse. The proportion of patients with an ELISA-BP230 value >=27 UA/ml
      was higher, but not significantly, for those with relapse than for those with
      remission (p = 0.11). The frequency of positive DIF findings was significantly
      higher for patients with relapse (p = 0.005). CONCLUSION: DIF is of better value
      than ELISA-BP180 and -230 tests to predict relapse after treatment cessation in
      BP.

PMID- 25871737
TI  - High levels of soluble MICA are significantly related to increased disease-free
      and disease-specific survival in patients with cervical adenocarcinoma.
AB  - Downregulation of major histocompatibility complex class I chain-related molecule
      A (MICA) and upregulation of human leukocyte antigen G (HLA-G) on the tumor cells
      are important immune escape mechanisms for different epithelial tumors. In
      addition, upregulation of the soluble forms of the latter molecules in serum
      leads to peripheral T-cell and natural killer (NK)-cell tolerance. As for
      cervical cancer, it remains unknown whether soluble MICA (sMICA) and soluble HLA
      G (sHLA-G) concentrations are related to tumor characteristics or patient
      survival rates. We measured sMICA and sHLA-G in pre-treatment sera of a large
      cohort of cervical cancer patients (n = 366) by enzyme-linked immunosorbent assay
      (ELISA). We detected a median sMICA of 174.73 pg/ml and a median sHLA-G of 5.35
      U/ml. We did not find an association between sHLA-G levels and
      clinicopathological characteristics. In adenocarcinoma, low sMICA concentration
      was positively related to recurrent disease, a higher International Federation of
      Gynecology and Obstetrics (FIGO) stage and vaginal involvement (Mann-Whitney U
      test; P = 0.018, P = 0.042 and P = 0.013, respectively). In the latter patient
      group, high sMICA levels were associated with better disease-free survival (DFS)
      and disease-specific survival (DSS) (P = 0.011 and P = 0.047). After adjusting
      for confounding factors, high sMICA proved to be an independent predictor for a
      better DFS and DSS [HR 0.16; 95% confidence interval (CI) 0.04-0.64; P = 0.009
      and HR 0.12; 95% CI 0.03-0.50; P = 0.004]. sHLA-G did not influence survival in
      cervical cancer patients, regardless of histology. We conclude that cervical
      adenocarcinoma patients with high sMICA levels have an increased DFS and DSS.
      This data warrants a prospective trial to study the functional role of sMICA in
      cervical adenocarcinoma. 

PMID- 25871738
TI  - Tobacco guard cells fix CO2 by both Rubisco and PEPcase while sucrose acts as a
      substrate during light-induced stomatal opening.
AB  - Transcriptomic and proteomic studies have improved our knowledge of guard cell
      function; however, metabolic changes in guard cells remain relatively poorly
      understood. Here we analysed metabolic changes in guard cell-enriched epidermal
      fragments from tobacco during light-induced stomatal opening. Increases in
      sucrose, glucose and fructose were observed during light-induced stomatal opening
      in the presence of sucrose in the medium while no changes in starch were
      observed, suggesting that the elevated fructose and glucose levels were a
      consequence of sucrose rather than starch breakdown. Conversely, reduction in
      sucrose was observed during light- plus potassium-induced stomatal opening.
      Concomitant with the decrease in sucrose, we observed an increase in the level as
      well as in the (13) C enrichment in metabolites of, or associated with, the
      tricarboxylic acid cycle following incubation of the guard cell-enriched
      preparations in (13) C-labelled bicarbonate. Collectively, the results obtained
      support the hypothesis that sucrose is catabolized within guard cells in order to
      provide carbon skeletons for organic acid production. Furthermore, they provide a
      qualitative demonstration that CO2 fixation occurs both via ribulose-1,5
      biphosphate carboxylase/oxygenase (Rubisco) and phosphoenolpyruvate carboxylase
      (PEPcase). The combined data are discussed with respect to current models of
      guard cell metabolism and function.

PMID- 25871739
TI  - Implementation and evaluation of the Johns Hopkins University School of Medicine
      leadership program for women faculty.
AB  - BACKGROUND: Women continue to be underrepresented in top leadership roles in
      academic medicine. Leadership training programs for women are designed to enhance
      women's leadership skills and confidence and increase overall leadership
      diversity. The authors present a description and evaluation of a longitudinal,
      cohort-based, experiential leadership program for women faculty at the Johns
      Hopkins University School of Medicine. METHODS: We compared pre- and post-program
      self-assessed ratings of 11 leadership skills and specific negotiation behaviors
      from 3 cohorts of leadership program participants (n=134) from 2010 to 2013.
      RESULTS: Women reported significant improvements in skills across 11 domains with
      the exceptions of 2 domains, Public Speaking and Working in Teams, both of which
      received high scores in the pre-program assessment. The greatest improvement in
      rankings occurred within the domain of negotiation skills. Although women
      reported an increase in their negotiation skills, we were not able to demonstrate
      an increase in the number of times that women negotiated for salary, space, or
      promotion following participation in the program. CONCLUSIONS: The Johns Hopkins
      School of Medicine Leadership Program for Women Faculty has demonstrable value
      for the professional development of participants and addresses institutional
      strategies to enhance leadership diversity and the advancement of women.

PMID- 25871740
TI  - Changes in cerebral blood flow in children with sickle cell disease after
      splenectomy.
AB  - The study assessed changes in cerebral blood flow and need for chronic blood
      transfusions in sickle cell disease children after splenectomy. A retrospective
      chart review of 40 children splenectomized between 1999 and 2014 was performed.
      The mean time-average maximum velocity before splenectomy was 129 cm/sec; which
      increased to 157 cm/sec and then decreased to 137 cm/sec, 2 and 5 years
      postsplenectomy, respectively. There was a persistent and statistically
      significant elevation in platelet count noted after splenectomy. The mean
      cerebral blood flow velocity seemed to increase transiently after splenectomy.
      Close monitoring and screening for stroke risk should be continued
      postsplenectomy.

PMID- 25871741
TI  - A facile approach to fabricate halloysite/metal nanocomposites with preformed and
      in situ synthesized metal nanoparticles: a comparative study of their enhanced
      catalytic activity.
AB  - A widespread study has been carried out by the researcher during the last few
      decades to improve the properties and performance of halloysite-based inorganic
      organic hybrid nanocomposites (NCs) because of their excellent structural
      features and characteristic properties. Here, we report the fabrication of
      halloysite/metal nanocomposites on a large-scale through the immobilization of
      metal precursors followed by reduction or direct loading of preformed metal
      nanoparticles (NPs) over the surface of aminosilane modified halloysite nanotubes
      (HNTs), which in turn develops environmentally benign and low-cost heterogeneous
      catalysts. Characterization by different physical methods authenticates the
      successful fabrication of four different HNTs/metal NCs by these two different
      synthetic approaches, having monodispersed spherical morphology of the metal NPs.
      The catalytic activity and recyclability of all the NCs have been evaluated
      considering the reduction of 4-nitrophenol using sodium borohydride as a model
      reaction, attributed to their almost comparable catalytic efficiency. However, a
      detailed kinetic study demonstrates the enhanced catalytic activity of in situ
      synthesized HNTs/Ag among the four NCs, owing to the absence of any capping
      materials over the surface of NPs. Activation energy, pre-exponential factor, and
      entropy of activation have been estimated for this reduction reaction. A
      comparison study of their catalytic activity has been carried out with the
      reported heterogeneous catalysts, indicating the higher activity of these NCs for
      the reduction of nitroaromatics. Nevertheless, such an outstanding catalytic
      efficiency was only observed for HNTs/Au and HNTs/Ag NCs, with no activity of
      HNTs or aminosilane modified HNTs. 

PMID- 25871743
TI  - Modulation of Nerve Injury-induced HDAC4 Cytoplasmic Retention Contributes to
      Neuropathic Pain in Rats.
AB  - BACKGROUND: The histone deacetylases (HDACs) have been implicated in pain
      hypersensitivity. This study investigated the potential involvement of an HDAC4
      related mechanism in the spinal nerve ligation (SNL)-induced nociceptive
      hypersensitivity. METHODS: The left L5 to L6 spinal nerves of 627 adult male
      Sprague-Dawley rats were surgically ligated. The withdrawal threshold of hind
      paws and the abundances, cellular location, and interactions of proteins in the
      dorsal horn were assayed before and after surgery. The 14-3-3beta-targeting small
      interfering RNA, a serum- and glucocorticoid-inducible kinase 1 (SGK1)
      antagonist, or an HDAC inhibitor was spinally injected to elucidate the role of
      14-3-3beta, SGK1, and HDAC4. RESULTS: Without affecting the HDAC4 level, SNL
      provoked SGK1 phosphorylation (mean +/- SEM from 0.24 +/- 0.02 to 0.78 +/- 0.06
      at day 7, n = 6), HDAC4 phosphorylation (from 0.38 +/- 0.03 to 0.72 +/- 0.06 at
      day 7, n = 6), 14-3-3beta expression (from 0.53 +/- 0.09 to 0.88 +/- 0.09 at day
      7, n = 6), cytoplasmic HDAC4 retention (from 1.18 +/- 0.16 to 1.92 +/- 0.11 at
      day 7, n = 6), and HDAC4-14-3-3beta coupling (approximately 2.4-fold) in the
      ipsilateral dorsal horn in association with behavioral allodynia. Knockdown of
      spinal 14-3-3beta expression prevented the SNL-provoked HDAC4 retention (from
      1.89 +/- 0.15 to 1.32 +/- 0.08 at day 7, n = 6), HDAC4-14-3-3beta coupling
      (approximately 0.6-fold above SNL 7D), and behavioral allodynia (from 0.16 +/-
      0.3 to 6 +/- 1.78 at day 7, n = 7), but not SGK1 (from 0.78 +/- 0.06 to 0.71 +/-
      0.04 at day 7, n = 6) or HDAC4 (from 0.75 +/- 0.15 to 0.68 +/- 0.11 at day 7, n =
      6) phosphorylation. CONCLUSION: Neuropathic pain maintenance involves the spinal
      SGK1 activation-dependent HDAC4 phosphorylation and its subsequent association
      with 14-3-3beta that promotes cytoplasmic HDAC4 retention in dorsal horn neurons.

PMID- 25871742
TI  - Surgical injury in the neonatal rat alters the adult pattern of descending
      modulation from the rostroventral medulla.
AB  - BACKGROUND: Neonatal pain and injury can alter long-term sensory thresholds.
      Descending rostroventral medulla (RVM) pathways can inhibit or facilitate spinal
      nociceptive processing in adulthood. As these pathways undergo significant
      postnatal maturation, the authors evaluated long-term effects of neonatal
      surgical injury on RVM descending modulation. METHODS: Plantar hind paw or
      forepaw incisions were performed in anesthetized postnatal day (P)3 Sprague
      Dawley rats. Controls received anesthesia only. Hind limb mechanical and thermal
      withdrawal thresholds were measured to 6 weeks of age (adult). Additional groups
      received pre- and post-incision sciatic nerve levobupivacaine or saline. Hind paw
      nociceptive reflex sensitivity was quantified in anesthetized adult rats using
      biceps femoris electromyography, and the effect of RVM electrical stimulation (5
      200 MUA) measured as percentage change from baseline. RESULTS: In adult rats with
      previous neonatal incision (n = 9), all intensities of RVM stimulation decreased
      hind limb reflex sensitivity, in contrast to the typical bimodal pattern of
      facilitation and inhibition with increasing RVM stimulus intensity in controls (n
      = 5) (uninjured vs. neonatally incised, P < 0.001). Neonatal incision of the
      contralateral hind paw or forepaw also resulted in RVM inhibition of hind paw
      nociceptive reflexes at all stimulation intensities. Behavioral mechanical
      threshold (mean +/- SEM, 28.1 +/- 8 vs. 21.3 +/- 1.2 g, P < 0.001) and thermal
      latency (7.1 +/- 0.4 vs. 5.3 +/- 0.3 s, P < 0.05) were increased in both hind
      paws after unilateral neonatal incision. Neonatal perioperative sciatic nerve
      blockade prevented injury-induced alterations in RVM descending control.
      CONCLUSIONS: Neonatal surgical injury alters the postnatal development of RVM
      descending control, resulting in a predominance of descending inhibition and
      generalized reduction in baseline reflex sensitivity. Prevention by local
      anesthetic blockade highlights the importance of neonatal perioperative
      analgesia.

PMID- 25871744
TI  - TGF-beta signalling prevents pancreatic beta cell death after proliferation.
AB  - OBJECTIVES: Maintenance of functional beta cell mass is critical for prevention
      of diabetes. The transforming growth factor-beta (TGF-beta) receptor signalling
      pathway plays an essential role in pancreatic development. However, its
      involvement in control of post-natal beta cell growth has only been recently
      reported. MATERIALS AND METHODS: Here, we studied the role of TGF-beta receptor
      signalling in beta cell proliferation after 50% partial pancreatectomy (PPx),
      using beta cell-specific TGF-beta receptor II (TBR2)-mutated mice. RESULTS:
      Consistent with previous reports, we found that inhibition of TGF-beta receptor
      signalling in beta cells resulted in slightly higher beta cell mass 1 week after
      PPx, due to greater beta cell proliferation. However, beta cell mass in these
      beta cell-specific TBR2-mutated mice significantly decreased by 12 weeks after
      PPx, resulting from increase in beta cell apoptosis. CONCLUSIONS: Our data thus
      suggest that TGF-beta receptor signalling may be required for prevention of beta
      cell death after proliferation, and highlight this pathway as an essential
      regulator during post-natal beta cell homoeostasis.

PMID- 25871745
TI  - Molecular series-tunneling junctions.
AB  - Charge transport through junctions consisting of insulating molecular units is a
      quantum phenomenon that cannot be described adequately by classical circuit laws.
      This paper explores tunneling current densities in self-assembled monolayer (SAM)
      based junctions with the structure Ag(TS)/O2C-R1-R2-H//Ga2O3/EGaIn, where Ag(TS)
      is template-stripped silver and EGaIn is the eutectic alloy of gallium and
      indium; R1 and R2 refer to two classes of insulating molecular units-(CH2)n and
      (C6H4)m-that are connected in series and have different tunneling decay constants
      in the Simmons equation. These junctions can be analyzed as a form of series
      tunneling junctions based on the observation that permuting the order of R1 and
      R2 in the junction does not alter the overall rate of charge transport. By using
      the Ag/O2C interface, this system decouples the highest occupied molecular
      orbital (HOMO, which is localized on the carboxylate group) from strong
      interactions with the R1 and R2 units. The differences in rates of tunneling are
      thus determined by the electronic structure of the groups R1 and R2; these
      differences are not influenced by the order of R1 and R2 in the SAM. In an
      electrical potential model that rationalizes this observation, R1 and R2
      contribute independently to the height of the barrier. This model explicitly
      assumes that contributions to rates of tunneling from the Ag(TS)/O2C and H//Ga2O3
      interfaces are constant across the series examined. The current density of these
      series-tunneling junctions can be described by J(V) = J0(V) exp(-beta1d1 -
      beta2d2), where J(V) is the current density (A/cm(2)) at applied voltage V and
      betai and di are the parameters describing the attenuation of the tunneling
      current through a rectangular tunneling barrier, with width d and a height
      related to the attenuation factor beta. 

PMID- 25871746
TI  - Fatal Hypersensitivity Pneumonitis from Exposure to Fusarium vasinfectum in a
      Home Environment: A Case Report.
AB  - BACKGROUND: Hypersensitivity pneumonitis (HP) is a rare, non-IgE-mediated
      inflammatory lung disease caused by inhalational exposure to various antigens
      found in occupational, avocational and home environments. The prognosis is
      favorable with early detection and prompt removal of the causative agent, and
      fatalities are unusual. We present a fatal case of HP caused by chronic exposure
      to Fusarium vasinfectum mold in the home. CASE REPORT: A 37-year-old white male
      presented with a 6-month history of progressively worsening dyspnea, cough,
      weight loss and fatigue associated with the self-renovation of his water-damaged,
      mold-infested mobile home. Evaluation included a physical examination (hypoxia,
      inspiratory crackles and expiratory rhonchi), baseline pulmonary function testing
      (mixed obstructive/restrictive pattern), chest computed tomography
      (bronchiectasis, fibrosis and diffuse interstitial involvement), bronchoalveolar
      lavage (macrophages 20%, lymphocytes 28% and neutrophils 52%) and transbronchial
      biopsy (interstitial fibrosis and chronic inflammatory infiltrate). Mold culture
      from the home grew out F. vasinfectum. An Ouchterlony double diffusion technique
      documented high antibody titer to F. vasinfectum. Despite aggressive intravenous
      corticosteroid treatment, the patient's lung function declined to the extent that
      he could not be removed from ventilator support following an open lung biopsy,
      eventually resulting in death. CONCLUSION: This is the first reported case of
      fatal HP related to an acute exacerbation of a chronic form of HP following
      continuous and intense exposure to F. vasinfectum. Although uncommon, a high
      index of suspicion for HP is necessary in patients with progressive respiratory
      symptoms and known environmental antigen exposure. With early detection and
      prompt removal of the causative antigen, HP prognosis is generally favorable, but
      can progress to fatal disease with continued exposure.

PMID- 25871747
TI  - Systematic Review of the Impact of Suicides and Other Critical Incidents on
      Railway Personnel.
AB  - The review summarizes current scientific knowledge on the effects of railway
      critical incidents on railway workers and the associated risk and protective
      factors. Diagnosable traumatic reactions sometimes occur after a serious
      incident. However, the most frequent effects are long-term impairments that do
      not meet diagnostic criteria but can still profoundly affect people's lives. Risk
      factors that can increase the negative effects of incidents include
      characteristics of the employee, coping mechanisms, the type of incident, and the
      support and care received. Prevention and intervention programs should consider
      the diversity of reactions to develop relevant support programs. 

PMID- 25871749
TI  - Avoid gender assumptions.

PMID- 25871748
TI  - Factors Predicting Recurrence of Clostridium difficile Infection (CDI) in
      Hospitalized Patients: Retrospective Study of More Than 2000 Patients.
AB  - BACKGROUND: Clostridium difficile infection (CDI) has increased in incidence and
      severity worldwide, causing direct costs estimated to range from US $3.2 billion
      to $4.8 billion. The aim of this study was to investigate and identify factors
      that predict recurrence of CDI. METHODS: This was a retrospective case-control
      study between 2007 and 2013 on patients admitted with CDI. Recurrent CDI is
      defined as a new episode of diarrhea within 90 days confirmed by a positive stool
      C. difficile toxin assay or polymerase chain reaction, after resolution of the
      initial CDI episode for at least 10 days and after discontinuation of the CDI
      therapy. RESULTS: Three thousand twenty patients were diagnosed with CDI between
      January 2007 and December 2013. Two hundred nine of 2019 patients in the study
      had a recurrence of CDI within 90 days of the end of the initial CDI episode
      (10.3%). Multivariate analysis showed that most of the recurrences occurred in
      patients with comorbidities, particularly chronic kidney disease (odds ratio,
      1.3; 95% confidence interval [CI], 1.0-2.4; P = 0.039). In addition, a higher
      percentage of patients in the recurrence group were prescribed proton-pump
      inhibitors (odds ratio, 1.65; 95% CI, 1.0-1.7; P = 0.002) and steroids (odds
      ratio, 1.65; 95% CI, 1.0-1.5; P = 0.047). CONCLUSIONS: Our data suggest that the
      use of glucocorticoids, use of proton-pump inhibitors, and having end-stage renal
      disease are significant risk factors associated with recurrent CDI.

PMID- 25871752
TI  - Can the family block organ donation?

PMID- 25871753
TI  - Virtual nursing grand rounds: Improving practice overseas.

PMID- 25871754
TI  - Considering a clinical faculty role? Strategies for success.

PMID- 25871755
TI  - Assessing patient awareness of proper hand hygiene.
AB  - BACKGROUND: The authors hypothesized that patients may not understand the forms
      of effective hand hygiene employed in the hospital environment. LITERATURE
      REVIEW: Multiple studies demonstrate the importance of hand hygiene in reducing
      healthcare-associated infections (HAIs). Extensive research about how to improve
      compliance has been conducted. METHODOLOGY: Patients' perceptions of proper hand
      hygiene were evaluated when caregivers used soap and water, waterless hand
      cleaner, or a combination of these. RESULTS: No significant differences were
      observed, but many patients reported they did not notice whether their providers
      cleaned their hands. DISCUSSION: Educating patients and their caregivers about
      the protection afforded by proper, consistent hand hygiene practices is
      important. IMPLICATIONS FOR NURSING PRACTICE: Engaging patients to monitor
      healthcare workers may increase compliance, reduce the spread of infection, and
      lead to better overall patient outcomes. IMPLICATIONS FOR RESEARCH: This study
      revealed a need to investigate the effects of patient education on patient
      perceptions of hand hygiene. CONCLUSION: Results of this study appear to indicate
      a need to focus on patient education and the differences between soap and water
      versus alcohol-based hand sanitizers as part of proper hand hygiene. Researchers
      could be asking: "Why have patients not been engaged as members of the healthcare
      team who have the most to lose?"

PMID- 25871759
TI  - Simple acts.

PMID- 25871760
TI  - Placental abruption: are we going to lose them both?

PMID- 25871761
TI  - Using a "tag team" approach to care for critically ill patients.

PMID- 25871762
TI  - Hold the phone? Nurses, social media, and patient care.

PMID- 25871763
TI  - Beta-blockers for patients undergoing CABG.

PMID- 25871767
TI  - Sterol Regulatory Element Binding Transcription Factor-1 Gene Variation and
      Medication Load Influence White Matter Structure in Schizophrenia.
AB  - BACKGROUND: Diffusion tensor imaging (DTI) studies have shown a widespread
      disruption of white matter (WM) microstructure in schizophrenia. Furthermore,
      higher fractional anisotropy (FA) has been consistently correlated with the
      severity of psychotic symptoms. Antipsychotic drugs (APDs) affect lipid
      homeostasis. Gene polymorphisms in sterol regulatory element binding
      transcription factor (SREBF)-1 and SREBF-2 have been associated with
      schizophrenia. METHODS: In a sample of 65 patients affected by chronic
      schizophrenia, we investigated the effect of ongoing APD medication, SREBF-1
      rs11868035 polymorphism and SREBF-2 rs1052717 polymorphism on the WM
      microstructure, using tract-based spatial statistics with threshold-free cluster
      enhancement. RESULTS: We reported increased FA associated with the risk
      rs11868035 G/G genotype in several WM tracts, mainly located in the left
      hemisphere, and opposite effects of the APD medication load, with reduced FA and
      generally increased diffusivity. These opposite effects overlapped in the forceps
      minor, cingulum, uncinate fasciculus, the superior and inferior longitudinal
      fasciculi, the corticospinal tract, inferior fronto-occipital fasciculus and the
      anterior thalamic radiation. CONCLUSION: We suggest that changes of WM structure
      could be an as yet poorly explored biomarker of the effects of APDs, to be
      further investigated in prospective studies correlating long-term clinical
      effects with changes of DTI measures in specific WM tracts contributing to the
      functional integrity of the brain. (c) 2015 S. Karger AG, Basel.

PMID- 25871768
TI  - Discovering structural alerts for mutagenicity using stable emerging molecular
      patterns.
AB  - This study is dedicated to the introduction of a novel method that automatically
      extracts potential structural alerts from a data set of molecules. These
      triggering structures can be further used for knowledge discovery and
      classification purposes. Computation of the structural alerts results from an
      implementation of a sophisticated workflow that integrates a graph mining tool
      guided by growth rate and stability. The growth rate is a well-established
      measurement of contrast between classes. Moreover, the extracted patterns
      correspond to formal concepts; the most robust patterns, named the stable
      emerging patterns (SEPs), can then be identified thanks to their stability, a new
      notion originating from the domain of formal concept analysis. All of these
      elements are explained in the paper from the point of view of computation. The
      method was applied to a molecular data set on mutagenicity. The experimental
      results demonstrate its efficiency: it automatically outputs a manageable number
      of structural patterns that are strongly related to mutagenicity. Moreover, a
      part of the resulting structures corresponds to already known structural alerts.
      Finally, an in-depth chemical analysis relying on these structures demonstrates
      how the method can initiate promising processes of chemical knowledge discovery. 

PMID- 25871769
TI  - Conservation of Helicity in a Chiral Pyrrol-2-yl Schiff-Base Ligand and Its
      Transition Metal Complexes.
AB  - Tetradentate enantiopure Schiff-base ligand (R,R) and (S,S)-bis(pyrrol-2
      ylmethyleneamine)-cyclohexane (H2L) and its five transition metal complexes with
      Ni(II), Cu(II), Zn(II), Pd(II), and Pt(II) were synthesized. Their structural
      properties, in particular, the ligand chirality, coordination topology, and the
      resulting helicity in solution, were investigated by using IR, vibrational
      circular dichroism (VCD), UV-vis, and electronic circular dichroism (ECD)
      spectroscopies, complemented with density functional theory calculations.
      Conformational searches and the associated spectral simulations for the ligands
      and the complexes were performed at the B3LYP/Gen level. Comparison of the
      experimental and theoretical IR and VCD spectral signatures of these complexes
      reveal that the Zn complex takes on a dinuclear, distorted tetrahedral
      coordination topology around the metal centers, whereas the other four metal
      complexes adopt the mononuclear, distorted square-planar coordination arrangement
      in solution. The helicity of all systems studied was identified to be M with the
      (R,R) ligand and P with the (S,S) ligand, dictated by the ligand chirality and
      the strong preference for the chair configuration by the cyclohexane moiety.
      Furthermore, the resulting helicity was found to dominate the ECD spectral
      features, even though the helicity-determining angles are close to zero for the
      nearly square-planar metal complexes. The related VCD spectral features are
      sensitive to both helicity of the complex and the chirality of the ligands, as
      well as the coordination topology. The simulated ECD spectra for the P and M
      helicity of the [Zn-(R,R)-L]2 complex shows almost mirror-imaged ECD spectral
      features, whereas very similar ECD spectra were recently reported for the P- and
      M-dinuclear Mn complexes with a di-MU-oxo dimetal core as a linker. We highlight
      the advantages of utilizing multiple chiroptical techniques and theoretical
      spectral simulations to correlate chiroptical spectral features with multiple
      chirality and helicity elements in the systems. 

PMID- 25871772
TI  - A Novel Microwave Catheter Can Perform Noncontact Circumferential Endocardial
      Ablation in a Model of Pulmonary Vein Isolation.
AB  - INTRODUCTION: Pulmonary vein isolation is an effective treatment for atrial
      fibrillation. Current endocardial ablation techniques require catheter contact
      for lesion formation. Inadequate or inconsistent catheter contact results in
      difficulty with achieving acute and long-term isolation and consequent atrial
      arrhythmia recurrence. Microwave energy produces radiant heating and therefore
      can be used for noncontact catheter ablation. We hypothesized that it is possible
      to design a microwave catheter to produce a circumferential transmural thermal
      lesion in an in vitro model of a pulmonary vein antrum. METHODS AND RESULTS: A
      monopole microwave catheter with a sideways firing axially symmetrical heating
      pattern was designed. Noncontact ablations were performed in a perfused pulmonary
      vein model constructed from microwave myocardial phantom embedded with a sheet of
      thermochromic liquid crystal to permit visualization and measurement of thermal
      lesions from color changes. 1200 J ablations were performed at 150 W for 80
      seconds and 120 W for 100 seconds at high (0.8 L/min) and low (0.06 L/min) flow
      through the modeled pulmonary vein. Myocardial tissue was substituted for the
      phantom material and ablations repeated at 150 W for 180 seconds and stained with
      nitro-blue tetrazolium. The catheter was able to induce deep circumferential
      antral lesions in myocardial phantom and myocardial tissue. Higher power and
      shorter ablations delivering the same amount of microwave energy resulted in
      larger lesions with less surface sparing. CONCLUSIONS: A microwave catheter can
      be designed to produce a circumferential thermal lesion on noncontact ablation
      and may have possible applications for pulmonary vein isolation.

PMID- 25871774
TI  - Polymorphism and evolution of ribosomal DNA in tea (Camellia sinensis, Theaceae).
AB  - Ribosomal DNA (rDNA) repeats often exhibit a high level of within-species
      homogeneity, but intra-individual polymorphism of rDNA has been found in Camellia
      species. In order to reveal the evolutionary pattern of rDNA repeats in tea
      [Camellia sinensis (L.) O. Kuntze], we identified the 45S rDNA loci, estimated
      their copy number, and cloned partial regions of them from different PCR products
      and from digested genomic DNA. The results show that there are 3 loci (6 sites)
      containing 45S rDNA in the tea genome; they are located at the ends of the short
      arms of 6 chromosomes and consist of a maximum of ~6500 repeat units. On one
      hand, 164 sequences of the 26S rDNA cloned from PCR products contained 147
      haplotypes, consisting of 62% pseudogenes, 24% putative functional genes, and 14%
      PCR-mediated recombinants, suggesting that the 45S rDNA of tea maintains an
      extremely high level of polymorphism and divergence; on the other hand, rDNA
      fragments cloned directly from genomic DNA exhibited a very high level of
      homogeneity: only one of 33 rDNA fragments was from a pseudogene. These results
      demonstrate that although over 60% of the 26S rDNA sequences identified in PCR
      products belong to pseudogenes, most 45S rDNA repeats are functional genes and
      have undergone concerted evolution. In this study, strong PCR bias and PCR
      mediated recombination greatly increased the apparent proportion of pseudogenes
      in PCR products. Phylogenetic analysis and genetic divergence values for 26S rDNA
      sequences obtained in this study show that many pseudogenes have originated
      independently from functional genes at different times, and despite thus escaping
      from concerted evolution, they have failed to be eliminated from the tea genome
      over a long period, some of them having even produced addition copies by rapid
      expansion. Importantly, our study suggests that in order to determine the true
      pattern of evolution of rDNA it is necessary to combine data from more than one
      method rather than relying only on sequences from PCR products. 

PMID- 25871773
TI  - Opposing effects of viral mediated brain expression of apolipoprotein E2 (apoE2)
      and apoE4 on apoE lipidation and Abeta metabolism in apoE4-targeted replacement
      mice.
AB  - BACKGROUND: Human apolipoprotein E (apoE) exists in three major isoforms: apoE2,
      apoE3 and apoE4. In the brain, apoE is produced mostly by astrocytes and
      transports cholesterol to neurons via apoE receptors. Among the gene alleles
      encoding the three isoforms, the APOE4 allele is the strongest genetic risk
      factor for late-onset Alzheimer's disease (AD), whereas APOE2 is protective.
      ApoE4 confers a gain of toxic function, a loss of neuroprotective function or a
      combination of both in AD pathogenesis. Given that therapeutic impacts of
      modulating apoE expression may be isoform-dependent, we sought to investigate the
      relationship between overexpressing apoE isoform and apoE-related functions in
      apoE-targeted replacement (TR) mice. Specifically, apoE isoform expression driven
      by the astrocyte-specific glial fibrillary acidic protein (GFAP) promoter was
      built into an adeno-associated virus serotype 8 (AAV8) vector and injected into
      the ventricles of postnatal day 2 (P2) apoE3-TR or apoE4-TR mice. Upon
      confirmation of apoE isoform expression, effects on apoE lipidation and the
      levels of amyloid-beta (Abeta) in the brain were assessed. RESULTS: AAV8-GFAP
      apoE isoforms were specifically expressed in astrocytes throughout all brain
      regions, which led to overall increased apoE levels in the brain. Viral mediated
      overexpression of apoE4 in the apoE4-TR background increased poorly-lipidated
      apoE lipoprotein particles and decreased apoE-associated cholesterol in apoE4-TR
      mice. Conversely, apoE2 overexpression in apoE4-TR mice enhanced apoE lipidation
      and associated cholesterol. Furthermore, overexpression of apoE4 elevated the
      levels of endogenous Abeta, whereas apoE2 overexpression trended to lower
      endogenous Abeta. CONCLUSIONS: Overexpression of apoE isoforms induces
      differential effects in the apoE4-TR background: apoE4 decreases apoE lipidation
      and enhances Abeta accumulation, whereas apoE2 has the opposite effects. Our
      findings suggest that increasing apoE2 in APOE4 carriers is a beneficial strategy
      to treat AD, whereas increasing apoE4 in APOE4 carriers is likely harmful. We
      have also established novel methods to express apoE isoforms in mouse brain to
      study apoE-related pathways in AD and related dementia.

PMID- 25871775
TI  - Conformational and Colloidal Stabilities of Isolated Constant Domains of Human
      Immunoglobulin G and Their Impact on Antibody Aggregation under Acidic
      Conditions.
AB  - Antibody therapeutics are now in widespread use and provide a new approach for
      treating serious diseases such as rheumatic diseases and cancer. Monoclonal
      antibodies used as therapeutic agents must be of high quality, and their safety
      must be guaranteed. Aggregated antibody is a degradation product that may be
      generated during the manufacturing process. To maintain the high quality and
      safety of antibody therapeutics, it is necessary to understand the mechanism of
      aggregation and to develop technologies to strictly control aggregate formation.
      Here, we extensively investigated the conformational and colloidal
      characteristics of isolated antibody constant domains, and provided insights into
      the molecular mechanism of antibody aggregation. Isolated domains (CH2, CH3, CL,
      and CH1-CL dimer) of human immunoglobulin G were synthesized, solubilized using
      49 sets of solution conditions (pH 2-8 and 0-300 mM NaCl), and characterized
      using circular dichroism, intrinsic tryptophan fluorescence, and dynamic light
      scattering. Salt-induced conformational changes and oligomer formation were
      kinetically analyzed by NaCl-jump measurements (from 0 to 300 mM at pH 3). Phase
      diagrams revealed that the domains have different conformational and colloidal
      stabilities. The unfolded fractions of CH3 and CH2 at pH 3 were larger than that
      of CL and CH1-CL dimer. The secondary and tertiary structures and particle sizes
      of CH3 and CH2 showed that, in non-native states, these domains were sensitive to
      salt concentration. Kinetic analyses suggest that oligomer formation by CH3 and
      CH2 proceeds through partially refolded conformations. The colloidal stability of
      CH3 in non-native states is the lowest of the four domains under the conditions
      tested. We propose that the impact of IgG constant domains on aggregation follows
      the order CH3 > CH2 > CH1-CL dimer > CL; furthermore, we suggest that CH3 plays
      the most critical role in driving intact antibody aggregation under acidic
      conditions. 

PMID- 25871776
TI  - SI113, a specific inhibitor of the Sgk1 kinase activity that counteracts cancer
      cell proliferation.
AB  - BACKGROUND/AIMS: Published observations on serum and glucocorticoid regulated
      kinase 1 (Sgk1) knockout murine models and Sgk1-specific RNA silencing in the RKO
      human colon carcinoma cell line point to this kinase as a central player in colon
      carcinogenesis and in resistance to taxanes. METHODS: By in vitro kinase activity
      inhibition assays, cell cycle and viability analysis in human cancer model
      systems, we describe the biologic effects of a recently identified kinase
      inhibitor, SI113, characterized by a substituted pyrazolo[3,4-d]pyrimidine
      scaffold, that shows specificity for Sgk1. RESULTS: SI113 was able to inhibit in
      vitro cell growth in cancer cells derived from tumors with different origins. In
      RKO cells, this kinase inhibitor blocked insulin-dependent phosphorylation of the
      Sgk1 substrate Mdm2, the main regulator of p53 protein stability, and induced
      necrosis and apoptosis when used as a single agent. Finally, SI113 potentiated
      the effects of paclitaxel on cell viability. CONCLUSION: Since SI113 appears to
      be effective in inducing cell death in RKO cells, potentiating paclitaxel
      sensitivity, we believe that this new molecule could be efficiently employed,
      alone or in combination with paclitaxel, in colon cancer chemotherapy.

PMID- 25871777
TI  - Aluminum-induced kinesin inactivation as potential molecular cause of impairment
      of neuronal transport processes.
AB  - It is commonly accepted that aluminum ions may initiate the development of
      diverse diseases, including neurological disorders. So far, our knowledge of the
      molecular mechanisms of the interaction of aluminum with defined cellular
      structures has been still fragmentary. As functional key tasks of neuronal cells
      essentially depend on the activity of kinesin, we wanted to find out whether this
      motor protein represents a molecular target for aluminum. We demonstrate that
      aluminum ions inhibit (IC50 ~50 MUM) the ATPase of the neuron-specific kinesin
      KIF5A. The ATPase-active center itself, which is located in the kinesin motor
      domain, does not seem to be directly affected by aluminum. Our results suggest
      that inhibition is preferentially caused by aluminum binding to some sequence
      within the kinesin stalk leading to a conformational state of the kinesin
      molecule, similar to those described in cases of kinesin autoinhibition caused by
      motor domain-tail binding. Because of the relative high sequence conservation of
      mammalian kinesin-1 (to which KIF5A belongs), we assume that also in non-neuronal
      cells the intracellular transport can be affected by aluminum ions.

PMID- 25871778
TI  - The low AGE diet: a neglected aspect of clinical nephrology practice?
AB  - Increasing evidence in the literature suggests an important role for advanced
      glycation end products (AGEs) in the generation of a state of increased oxidative
      stress and chronic subclinical inflammation, which underlies most modern chronic
      diseases, including diabetes, cardiovascular disease and chronic kidney disease
      (CKD). Although AGEs were originally thought to form only endogenously, primarily
      as the result of the hyperglycemia of diabetes, it is now clear that exogenous
      AGEs, specially incorporated in foods, are an important contributor to the body
      pool of AGEs. Over the past decade, several clinical trials have been performed
      in a variety of conditions demonstrating that the application of an AGE
      restricted diet reduces not only the systemic levels of AGEs but also the levels
      of markers of oxidative stress and inflammation. This has been shown in CKD
      patients before and after the initiation of dialysis and either in the presence
      or absence of coexistent diabetes. Reduction of the AGE content in food is
      obtained by simple changes in culinary techniques and appears to be a feasible,
      easily applicable and safe intervention, even in advanced CKD patients.

PMID- 25871779
TI  - Systems Biology Modeling of Five Pathways for Regulation and Potent Inhibition of
      the Anaphase-Promoting Complex (APC/C): Pivotal Roles for MCC and BubR1.
AB  - Correct DNA segregation is a fundamental process that ensures the precise and
      reliable inheritance of genomic information for the propagation of cell life.
      Eukaryotic cells have evolved a conserved surveillance control mechanism for DNA
      segregation named the Spindle Assembly Checkpoint (SAC).The SAC ensures that the
      sister chromatids of the duplicated genome are not separated and distributed to
      the spindle poles before all chromosomes have been properly linked to the
      microtubules of the mitotic spindle. Biochemically, the SAC delays cell cycle
      progression by preventing activation of the anaphase-promoting complex (APC/C) or
      cyclosome whose activation by Cdc20 is required for sister-chromatid separation;
      this marks the transition into anaphase. In response to activation of the
      checkpoint, various species control the activity of both APC/C and Cdc20.
      However, the underlying regulatory pathways remain largely elusive. In this
      study, five possible model variants of APC/C regulation were constructed, namely
      BubR1, Mad2, MCC, MCF2, and an all-pathways model variant. These models were
      validated with experimental data from the literature. A wide range of parameter
      values has been tested to find the critical values of the APC/C binding rate. The
      results show that all variants are able to capture the wild-type behavior of the
      APC/C. However, only one model variant, which included both MCC as well as BubR1
      as potent inhibitors of the APC/C, was able to reproduce both wild-type and
      mutant type behavior of APC/C regulation. In conclusion, the presented work
      informs the regulation of fundamental processes such as SAC and APC/C in cell
      biology and has successfully distinguished between five competing dynamical
      models using a systems biology approach. The results attest that systems-level
      approaches are vital for molecular and cell biology. 

PMID- 25871780
TI  - Time to Event Analysis for the Development of Venous Thromboembolism After Spinal
      Fusion >= 5 Levels.
AB  - OBJECTIVE: Venous thromboembolism (VTE) is an important complication after spine
      surgery with an incidence of 31%. To our knowledge, no study has reported a time
      dependent examination of factors influencing VTE. We report factors influencing
      first and multiple VTE events and perform a time-dependent analysis. METHODS: A
      retrospective analysis was performed of consecutive, "high-risk" patients
      receiving multilevel spinal fusion and an inferior vena cava (IVC) filter during
      the period 2000-2008. Descriptive statistics and frequencies were examined.
      Student t tests and logistic regression analysis identified confounders
      influencing development of acute VTE. Kaplan-Meier survival and Cox proportional
      hazard model evaluated time-dependent risk factors. Multivariate linear
      regression model analyzed multiple acute VTE events. RESULTS: There were 218
      patients (149 women and 69 men) with an average age of 59.2 years (range, 18-86
      years) who had 252 hospitalizations with an average stay of 20.3 days (SD =
      15.6). There were 72 VTE events, with mean time to VTE of 15 days (SD = 18.1).
      Logistic regression identified factors influencing development of acute VTE,
      including sex (P = 0.04, OR = 0.243), VTE history (P = 0.001, OR = 8.0), IVC
      filter type (P = 0.050, OR = 15.6), chemoprophylaxis (P = 0.013, OR = 0.82), and
      hospital stay (P < 0.001, OR = 0.16). Kaplan-Meier curve revealed VTE history
      increased the rate of VTE development (P = 0.003). Cox proportional hazard model
      demonstrated IVC filter type (P = 0.003, hazard ratio = 5.042) and VTE history (P
      = 0.001, hazard ratio = 4.187) were significant for first VTE events. Linear
      regression analysis identified factors influencing development of multiple VTE
      events during a hospitalization, including VTE history (P < 0.01),
      chemoprophylaxis (P = 0.003), IVC filter type (P = 0.015), and hospital stay (P <
      0.001). Mean and median follow-up were 3.3 years and 2.8 years, respectively.
      CONCLUSIONS: Sex, VTE history, IVC filter type, chemoprophylaxis, and hospital
      stay influenced development of VTE. Time to VTE correlated with DVT history and
      IVC filter type, whereas VTE history and hospital stay influenced multiple VTE
      events.

PMID- 25871781
TI  - Middle Cerebral Artery Bifurcation Aneurysms: When and How to Treat Asymptomatic
      Unruptured Aneurysms.

PMID- 25871782
TI  - Infundibular Recess Angle Reduction After Endoscopic Third Ventriculostomy: Does
      It Reflect Clinical Success?
AB  - BACKGROUND: Although the ventricular size is significantly reduced after
      endoscopic third ventriculostomy (ETV) in most successfully treated patients,
      ventricular size reduction is not always seen after a successful ETV. Practical
      and reliable radiologic parameters are still needed to assess the clinical
      success of an ETV. METHODS: We retrieved the clinical and radiologic data of
      patients who underwent an ETV. Patients with the following criteria were
      included: (1) preoperative magnetic resonance imaging studies available, (2)
      postoperative magnetic resonance imaging studies done within the first 2
      postoperative weeks, and (3) the infundibular recess clearly visible on
      preoperative and postoperative sagittal magnetic resonance imaging. Preoperative
      and postoperative measurements of the angle of the infundibular recess of the
      third ventricle were performed on midsagittal T1-weighted, T2-weighted, fast
      imaging employing steady-state acquisition, or constructive interference in
      steady state images. RESULTS: The extent of reduction of the infundibular recess
      angle predicted the clinical outcome of ETV during the early postoperative period
      with a high degree of accuracy. The average reduction was about 48% in successful
      procedures versus only 15% in failed procedures. CONCLUSIONS: The degree of
      reduction of the angle of the infundibular recess of the third ventricle
      correlated with the amount of third ventricular decompression after ETV. Most
      importantly, such a reduction was noted to occur during the early postoperative
      period when radiologic changes are less pronounced. Assessment of change in
      infundibular recess angle measurement is easy to perform and may prove helpful in
      cases with no clear-cut clinical evidence of success of ETV.

PMID- 25871784
TI  - Treatment of Unruptured Middle Cerebral Artery Aneurysms: The Risk Factors and
      Surgical Safety.

PMID- 25871783
TI  - Treatment Strategy for Bilateral Severe Carotid Artery Stenosis: One Center's
      Experience.
AB  - OBJECTIVE: To describe 1 center's experience using carotid artery stenting (CAS)
      or carotid endarterectomy (CEA) as a treatment strategy in patients with
      bilateral carotid artery stenosis. METHODS: Patients with severe carotid artery
      stenosis, including bilateral carotid artery stenosis, treated by CEA or CAS
      during the period 2008-2013 were reviewed retrospectively. The selection of
      treatment depended on the individual patient's medical comorbidities, neurologic
      condition, and clinical and anatomic arterial factors. The main adverse events
      included death from any cause, major stroke within 30 days, and death between 30
      days and 1 year later from the treated carotid artery or ipsilateral major
      stroke. RESULTS: There were 27 patients with bilateral carotid artery stenosis
      treated, including 11 patients with bilateral CEA, 9 patients with CEA on one
      side and CAS on the other side, and 7 patients with bilateral CAS. Of patients
      with unilateral carotid artery stenosis, 69 were treated with CEA, and 75 were
      treated with CAS. The incidence of main adverse events for the bilateral patients
      was 7.4%, similar to the unilateral patients undergoing CEA and CAS (8.7% and
      6.7%, respectively). Restenosis occurred in 4 treated carotid arteries in
      bilateral patients within 1 year (4 of 54 [7.4%]); this was not significantly
      different from unilateral patients undergoing CEA and CAS (4 of 69 [5.8%] and 6
      of 75 [8.0%], respectively). Local complications were not more frequent in
      bilateral patients. CONCLUSIONS: Good outcomes can be achieved in patients with
      bilateral carotid artery stenosis when treatment selection is based on each
      individual patient's clinical characteristics and with a proper combination of
      staged CEA and CAS.

PMID- 25871785
TI  - In vitro Activity of Cefditoren against Middle Ear Fluid Isolates from Costa
      Rican Children with Otitis Media.
AB  - Otitis media (OM) is one of the most common infections in children, Streptococcus
      pneumoniae and nontypable Haemophilus influenzae being the two most common
      pathogens isolated in the middle ear fluid (MEF) of children with OM. Cefditoren
      is a third-generation cephalosporin with broad-spectrum antibacterial activity,
      including activity against those pathogens commonly causing OM, with enhanced
      stability against common beta-lactamases. The main objective of this study was to
      evaluate the in vitro activity of cefditoren against pathogens collected from the
      MEF of Costa Rican children with OM between 2006 and 2011. A total of 715 samples
      were analyzed. Among the 89 S. pneumoniae strains that were penicillin
      nonsusceptible, only 7% were cefditoren-resistant according to Spanish Regulatory
      Agency criteria; among the H. influenza and M. catarrhalis isolates obtained, 100
      and 90% of the isolates, respectively, were cefditoren-susceptible. MIC50/90
      against the 207 PCV-13 S. pneumoniae serotyped strains and the 79 serotypes not
      covered by PCV-13 for cefditoren were 0.03/1 and 0.03/0.12 mg/l, respectively.
      For both amoxicillin-susceptible and resistant H. influenzae strains, the MIC
      range against cefditoren was from <=0.015 to 0.06 mg/l as well. In conclusion,
      the confirmation of the wide spectrum of activity of cefditoren and its intrinsic
      strength against resistant strains allows us to suggest that cefditoren might be
      included as one of the best choices among antibiotics that are widely used in
      empiric therapy for OM in pediatric patients.

PMID- 25871787
TI  - Hollow core-shell structured Ni-Sn@C nanoparticles: a novel electrocatalyst for
      the hydrogen evolution reaction.
AB  - Pt-free electrocatalysts with high activity and low cost are highly pursued for
      hydrogen production by electrochemically splitting water. Ni-based alloy
      catalysts are potential candidates for the hydrogen evolution reaction (HER) and
      have been studied extensively. Here, we synthesized novel hollow core-shell
      structure Ni-Sn@C nanoparticles (NPs) by sol-gel, chemical vapor deposition, and
      etching processes. The prepared electrocatalysts with porous hollow carbon layers
      have a high conductivity and large active area, which exhibit good
      electrocatalytic activity toward HER. The Tafel slope of ~35 millivolts per
      decade measured in acidic solution for Ni-Sn@C NPs is the smallest one to date
      for the Ni-Sn alloy catalysts, and exceeds those of the most non-noble metal
      catalysts, indicating a possible Volmer-Heyrovsky reaction mechanism. The
      synthetic method can be extended to prepare other hollow core-shell structure
      electrocatalysts for low-temperature fuel cells. 

PMID- 25871786
TI  - E-Learning in Urology: Implementation of the Learning and Teaching Platform
      CASUS(r) - Do Virtual Patients Lead to Improved Learning Outcomes? A Randomized
      Study among Students.
AB  - BACKGROUND: E-learning is playing an increasing role in medical education,
      supporting a problem-based and practical oriented education without putting
      patients at risk and compensating for the decrease in instructor-centered
      teaching. Not much research has been done concerning learning effects and
      reaction on behalf of the students. METHODS: We created computer-based cases for
      four important diagnoses in urology using the authoring system CASUS(r). Fourth
      year medical school students were randomized into two groups: (1) the CASUS(r)
      group, using the online cases for preparation, and (2) the book group, using a
      textbook. A multiple-choice test referring to the prepared topic had to be
      completed at the beginning of each lecture and the results were analyzed.
      Evaluation of the students concerning the acceptance of the program was done at
      the end of the semester. RESULTS: Members of the CASUS(r) group scored
      significantly higher with an average of 20% better test results than students
      using textbooks for preparation. Evaluation regarding the program showed a highly
      positive rating. Limitations include the small study population and the possibly
      biased test performance of the students. CONCLUSION: Computerized patient cases
      facilitate practice-oriented teaching and result in an interesting and engaging
      learning model with improved learning outcomes.

PMID- 25871788
TI  - Morphological, molecular and phylogenetic analyses of the spirurid nematode
      Stegophorus macronectes (Johnston & Mawson, 1942).
AB  - Stegophorus macronectes (Johnston & Mawson, 1942) is a gastrointestinal parasite
      found in Antarctic seabirds. The original description of the species, which was
      based only on females, is poor and fragmented with some unclear diagnostic
      characters. This study provides new morphometric and molecular data on this
      previously poorly described parasite. Nuclear rDNA sequences (18S, 5.8S, 28S and
      internal transcribed spacer (ITS) regions) were isolated from S. macronectes
      specimens collected from the chinstrap penguin Pygoscelis antarctica Forster on
      Deception Island, Antarctica. Using 18S rDNA sequences, phylogenetic analyses
      (maximum likelihood, maximum parsimony and Bayesian inference) of the order
      Spirurida were performed to determine the phylogenetic location of this species.
      Primer pairs of the ITS regions were designed for genus-level identification of
      specimens, regardless of their cycle, as an alternative to coprological methods.
      The utility of this molecular method for identification of morphologically
      altered specimens is also discussed. 

PMID- 25871789
TI  - Association between serum osteocalcin level and visceral obesity in Chinese
      postmenopausal women.
AB  - BACKGROUND: A low serum osteocalcin level, visceral obesity and postmenopausal
      status are recognized risk factors for cardiovascular disease. OBJECTIVE: We
      investigated the relationship between the serum osteocalcin level and visceral
      fat content in a population of Chinese postmenopausal women. DESIGN AND PATIENTS:
      In total, 1481 postmenopausal women (mean age +/- standard deviation, 57.1 +/-
      4.8 years) were selected from the Shanghai Obesity Study. MEASUREMENTS: Abdominal
      fat accumulation was quantified using magnetic resonance imaging. Subjects with a
      visceral fat area (VFA) of >=80 cm(2) were classified as abdominally obese. The
      total serum osteocalcin level was measured by electrochemiluminescence
      immunoassay. RESULTS: The median serum osteocalcin level was 20.66 MUg/l
      (interquartile range, 16.88-25.42 MUg/l). The overall prevalence of abdominal
      obesity was 49.1% (n = 727). Abdominally obese subjects had lower serum
      osteocalcin levels than did nonabdominally obese subjects [19.14 (16.02-23.82) vs
      21.97 (18.14-26.77) MUg/l, respectively; P < 0.001]. Partial correlation analysis
      showed that the serum osteocalcin level was still negatively correlated with VFA
      after adjusting for age, years since menopause and body mass index (P < 0.01).
      Moreover, VFA was independently associated with the serum osteocalcin level after
      adjustment for confounding factors (P < 0.05). A low serum osteocalcin level was
      an independent risk factor for abdominal obesity (odds ratio, 0.972; 95%
      confidence interval, 0.953-0.991; P = 0.004). CONCLUSION: The serum osteocalcin
      level was inversely correlated with the visceral fat content in these Chinese
      postmenopausal women.

PMID- 25871790
TI  - QCT Volumetric Bone Mineral Density and Vascular and Valvular Calcification: The
      Framingham Study.
AB  - There is increasing evidence that bone and vascular calcification share common
      pathogenesis. Little is known about potential links between bone and valvular
      calcification. The purpose of this study was to determine the association between
      spine bone mineral density (BMD) and vascular and valvular calcification.
      Participants included 1317 participants (689 women, 628 men) in the Framingham
      Offspring Study (mean age 60 years). Integral, trabecular, and cortical
      volumetric bone density (vBMD) and arterial and valvular calcification were
      measured from computed tomography (CT) scans and categorized by sex-specific
      quartiles (Q4 = high vBMD). Calcification of the coronary arteries (CAC),
      abdominal aorta (AAC), aortic valve (AVC), and mitral valve (MVC) were quantified
      using the Agatston Score (AS). Prevalence of any calcium (AS >0) was 69% for CAC,
      81% for AAC, 39% for AVC, and 20% for MVC. In women, CAC increased with
      decreasing quartile of trabecular vBMD: adjusted mean CAC = 2.1 (Q4), 2.2 (Q3),
      2.5 (Q2), 2.6 (Q1); trend p = 0.04. However, there was no inverse trend between
      CAC and trabecular vBMD in men: CAC = 4.3 (Q4), 4.3 (Q3), 4.2 (Q2), 4.3 (Q1);
      trend p = 0.92. AAC increased with decreasing quartile of trabecular vBMD in both
      women (AAC = 4.5 [Q4], 4.8 [Q3], 5.4 [Q2], 5.1 [Q1]; trend p = 0.01) and men (AAC
      = 5.5 [Q4], 5.8 [Q3], 5.9 [Q2], 6.2 [Q1]; trend p = 0.01). We observed no
      association between trabecular vBMD and AVC or MVC in women or men. Finally,
      cortical vBMD was unrelated to vascular calcification and valvular calcification
      in women and men. Women and men with low spine vBMD have greater severity of
      vascular calcification, particularly at the abdominal aorta. The inverse relation
      between AAC and spine vBMD in women and men may be attributable to shared
      etiology and may be an important link on which to focus treatment efforts that
      can target individuals at high risk of both fracture and cardiovascular events.

PMID- 25871791
TI  - Exogenous treatment with eicosapentaenoic acid supports maturation of
      cardiomyocytes derived from embryonic stem cells.
AB  - Embryonic stem cells offer multiple advantages over adult stem cells in terms of
      achieving acceptable number of functional cardiomyocytes to be exploited in cell
      therapy. However, differentiation efficacy is still a major issue to be solved
      before moving to regenerative medicine. Although a vast number of chemical
      compounds have been tested on efficiency of cardiac differentiation, the effect
      of fish oil components, such as eicosapentaenoic acid (EPA) on developmental
      bioenergetics, and hence cardiac differentiation, remained unstudied. EPA has
      been reported to have several cardioprotective effects, but there is no study
      addressing its role in cardiac differentiation. After mesoderm induction of
      embryoid bodies (EBs) derived from mouse embryonic stem cells (mESCs) in hanging
      drops initiated by ascorbic acid, they were treated with various concentrations
      of EPA. Gene and protein expression and functional properties of cardiomyocytes
      derived from ESCs were evaluated following treatment with various concentrations
      of EPA. Exposure to low concentrations of EPA (10 MUM) increased percentage of
      beating colonies and beating area. This treatment also resulted in up to 3 fold
      increase in expression of NKX2-5, MEF2C, MYH6, TNNT2 and CX43. FACS analysis
      confirmed gene expression analysis with increased percentage of MYH6 positive
      cells in EPA-treated group compared to the control group. In contrast, the
      expression of genes coding for cardiac differentiation, remained constant or even
      declined with higher concentrations of EPA. In conclusion, we have demonstrated
      that treatment of mESCs undergoing cardiac differentiation with low
      concentration, but not high concentration of EPA up-regulate transcription of
      genes associated with cardiac development. 

PMID- 25871792
TI  - The small GTPase Rab33A participates in regulation of amylase release from
      parotid acinar cells.
AB  - Amylase is released from exocrine parotid acinar cells via typical exocytosis.
      Exocytosis of amylase-containing granules occurs through several steps, including
      formation, maturation, and transport of granules. These steps are thought to be
      regulated by members of the small GTPase Rab family. We previously demonstrated
      that Rab27 and its effectors mediate amylase release from parotid acinar cells,
      but the functional involvement of other Rab proteins in exocrine granule
      exocytosis remains largely unknown. Here, we studied isoproterenol (IPR)-induced
      amylase release from parotid acinar cells to investigate the possible involvement
      of Rab33A, which was recently suggested to regulate exocytosis in hippocampal
      neurons and PC12 cells. Rab33A was endogenously expressed in parotid acinar cells
      and present in secretory granules and the Golgi body. Functional ablation of
      Rab33A with anti-Rab33A antibody or a dominant-negative Rab33A-T50N mutant
      significantly reduced IPR-induced amylase release. Our results indicated that
      Rab33A is a novel component of IPR-stimulated amylase secretion from parotid
      acinar cells. 

PMID- 25871793
TI  - Acid-base balance and changes in haemolymph properties of the South African rock
      lobsters, Jasus lalandii, a palinurid decapod, during chronic hypercapnia.
AB  - Few studies exist reporting on long-term exposure of crustaceans to hypercapnia.
      We exposed juvenile South African rock lobsters, Jasus lalandii, to hypercapnic
      conditions of pH 7.3 for 28 weeks and subsequently analysed changes in the
      extracellular fluid (haemolymph). Results revealed, for the first time,
      adjustments in the haemolymph of a palinurid crustacean during chronic
      hypercapnic exposure: 1) acid-base balance was adjusted and sustained by
      increased bicarbonate and 2) quantity and oxygen binding properties of
      haemocyanin changed. Compared with lobsters kept under normocapnic conditions (pH
      8.0), during prolonged hypercapnia, juvenile lobsters increased bicarbonate
      buffering of haemolymph. This is necessary to provide optimum pH conditions for
      oxygen binding of haemocyanin and functioning of respiration in the presence of a
      strong Bohr Effect. Furthermore, modification of the intrinsic structure of the
      haemocyanin molecule, and not the presence of molecular modulators, seems to
      improve oxygen affinity under conditions of elevated pCO2. 

PMID- 25871794
TI  - Nutlin-3 down-regulates retinoblastoma protein expression and inhibits muscle
      cell differentiation.
AB  - The p53 tumor suppressor gene plays a critical role in regulation of
      proliferation, cell death and differentiation. The MDM2 oncoprotein is a major
      negative regulator for p53 by binding to and targeting p53 for proteasome
      mediated degradation. The small molecule inhibitor, nutlin-3, disrupts MDM2-p53
      interaction resulting in stabilization and activation of p53 protein. We have
      previously shown that nutlin-3 activates p53, leading to MDM2 accumulation as
      concomitant of reduced retinoblastoma (Rb) protein stability. It is well known
      that Rb is important in muscle development and myoblast differentiation and that
      rhabdomyosarcoma (RMS), or cancer of the skeletal muscle, typically harbors MDM2
      amplification. In this study, we show that nutlin-3 inhibited myoblast
      proliferation and effectively prevented myoblast differentiation, as evidenced by
      lack of expression of muscle differentiation markers including myogenin and
      myosin heavy chain (MyHC), as well as a failure to form multinucleated myotubes,
      which were associated with dramatic increases in MDM2 expression and decrease in
      Rb protein levels. These results indicate that nutlin-3 can effectively inhibit
      muscle cell differentiation. 

PMID- 25871795
TI  - Off-response in ASH neurons evoked by CuSO4 requires the TRP channel OSM-9 in
      Caenorhabditis elegans.
AB  - The off-response of ASH neurons had been overlooked until the microfluidic
      devices were introduced for in vivo imaging of neuronal activity in
      Caenorhabditis elegans. The mechanisms of ASH off-response were completely
      unknown. Here we monitored ASH off-response to CuSO4 stimulation by use of
      microfluidic device and genetically encoded calcium indicator (GECI) - Case12. We
      found ASH neurons exhibited a multiphasic response to 10 mM and 50 mM CuSO4 of 30
      s stimulation duration. ASH off-responding to Cu(2+) had been dramatically
      reduced in goa-1, mod-5, trpa-1 and egl-8 mutants. Moreover, in osm-9 mutants ASH
      off-response was completely eliminated. Neuron-specific rescue of osm-9 in ASH
      neurons restored the off-response and the normal avoidance behavior in worms. 

PMID- 25871796
TI  - CCN3 overexpression inhibits growth of callosal projections via upregulation of
      RAB25.
AB  - The cysteine-rich 61/connective tissue growth factor 3 (CCN3) is a member of the
      CCN family of secreted multifunctional proteins involved in a variety of cellular
      processes including migration, adhesion, and differentiation. Previous studies
      have shown that CCN3 is expressed in the developing rat central nervous system,
      and enhanced CCN3 expression is highly correlated with tumorigenesis. However,
      the expression pattern and influence of abnormal CCN3 expression during mouse
      cortical development remains to be elucidated. Here, we show that CCN3 expression
      in mice is first detectable at embryonic day 15 and increases until postnatal day
      21. We overexpressed CCN3 in mouse cortical neurons using uni- and bilateral
      electroporation. Our in vivo overexpression experiments showed that elevated CCN3
      expression inhibited the axonal outgrowth of callosal projection neurons.
      Moreover, we identified the small GTPase RAB25 as a downstream effector molecule
      of CCN3 using transcriptomic analysis with CCN3 overexpressed in cortical tissue.
      In vivo ectopic expression of RAB25 or the dominant-negative RAB25-T26N also
      revealed that the GTPase activity of RAB25 is involved in the CCN3-mediated
      regulation of neuronal outgrowth. Taken together, our results suggest that tight
      regulation of CCN3 expression is necessary for normal cortical neuronal
      connectivity during development, and RAB25 negatively regulates neuronal
      differentiation as a downstream effector of CCN3. 

PMID- 25871797
TI  - Two specific membrane-bound aminopeptidase N isoforms from Aedes aegypti larvae
      serve as functional receptors for the Bacillus thuringiensis Cry4Ba toxin
      implicating counterpart specificity.
AB  - The interaction between Bacillus thuringiensis Cry toxins and their receptors on
      midgut cells of susceptible insect larvae is the critical determinant in toxin
      specificity. Besides GPI-linked alkaline phosphatase in Aedes aegypti mosquito
      larval midguts, membrane-bound aminopeptidase N (AaeAPN) is widely thought to
      serve as a Cry4Ba receptor. Here, two full-length AaeAPN isoforms, AaeAPN2778 and
      AaeAPN2783, predicted to be GPI-linked were cloned and successfully expressed in
      Spodoptera frugiperda (Sf9) cells as 112- and 107-kDa membrane-bound proteins,
      respectively. In the cytotoxicity assay, Sf9 cells expressing each of the two
      AaeAPN isoforms showed increased sensitivity to the Cry4Ba mosquito-active toxin.
      Double immunolocalization revealed specific binding of Cry4Ba to each individual
      AaeAPN expressed on the cell membrane surface. Sequence analysis and homology
      based modeling placed these two AaeAPNs to the M1 aminopeptidase family as they
      showed similar four-domain structures, with the most conserved domain II being
      the catalytic component. Additionally, the most variable domain IV containing
      negatively charged surface patches observed only in dipteran APNs could be
      involved in insect specificity. Overall results demonstrated that these two
      membrane-bound APN isoforms were responsible for mediating Cry4Ba toxicity
      against AaeAPN-expressed Sf9 cells, suggesting their important role as functional
      receptors for the toxin counterpart in A. aegypti mosquito larvae. 

PMID- 25871798
TI  - Human monocytes and macrophages express NADPH oxidase 5; a potential source of
      reactive oxygen species in atherosclerosis.
AB  - Monocytes (Mon) and Mon-derived macrophages (Mac) orchestrate important oxidative
      and inflammatory reactions in atherosclerosis by secreting reactive oxygen
      species (ROS) due, in large part, to the upregulated NADPH oxidases (Nox). The
      Nox enzymes have been extensively investigated in human Mon and Mac. However, the
      expression and functional significance of the Nox5 subtypes is not known. We
      aimed at elucidating whether Nox5 is expressed in human Mon and Mac, and examine
      its potential role in atherosclerosis. Human monocytic THP-1 cell line and
      CD14(+) Mon were employed to search for Nox5 expression. RT-PCR, Western blot,
      lucigenin-enhanced chemiluminescence and dihydroethidium assays were utilized to
      examine Nox5 in these cells. We found that Nox5 transcription variants and
      proteins are constitutively expressed in THP-1 cells and primary CD14(+) Mon.
      Silencing of Nox5 protein expression by siRNA reduced the Ca(2+)-dependent Nox
      activity and the formation of ROS in Mac induced by A23187, a selective Ca(2+)
      ionophore. Exposure of Mac to increasing concentrations of IFNgamma (5-100 ng/ml)
      or oxidized LDL (5-100 MUg/ml) resulted in a dose-dependent increase in Nox5
      protein expression and elevation in intracellular Ca(2+) concentration.
      Immunohistochemical staining revealed that Nox5 is present in CD68(+) Mac-rich
      area within human carotid artery atherosclerotic plaques. To the best of our
      knowledge, this is the first evidence that Nox5 is constitutively expressed in
      human Mon. Induction of Nox5 expression in IFNgamma- and oxidized LDL-exposed Mac
      and the presence of Nox5 in Mac-rich atheroma are indicative of the implication
      of Nox5 in atherogenesis. 

PMID- 25871799
TI  - Activation of AMPA receptor promotes TNF-alpha release via the ROS-cSrc-NFkappaB
      signaling cascade in RAW264.7 macrophages.
AB  - The relationship between glutamate signaling and inflammation has not been well
      defined. This study aimed to investigate the role of AMPA receptor (AMPAR) in the
      expression and release of tumor necrosis factor-alpha (TNF-alpha) from
      macrophages and the underlying mechanisms. A series of approaches, including
      confocal microscopy, immunofluorescency, flow cytometry, ELISA and Western
      blotting, were used to estimate the expression of AMPAR and downstream signaling
      molecules, TNF-alpha release and reactive oxygen species (ROS) generation in the
      macrophage-like RAW264.7 cells. The results demonstrated that AMPAR was expressed
      in RAW264.7 cells. AMPA significantly enhanced TNF-alpha release from RAW264.7
      cells, and this effect was abolished by CNQX (AMPAR antagonist). AMPA also
      induced elevation of ROS production, phosphorylation of c-Src and activation of
      nuclear factor (NF)-kappaB in RAW264.7 cells. Blocking c-Src by PP2, scavenging
      ROS by glutathione (GSH) or inhibiting NF-kappaB activation by pyrrolidine
      dithiocarbamate (PDTC) decreased TNF-alpha production from RAW264.7 cells. We
      concluded that AMPA promotes TNF-alpha release in RAW264.7 macrophages likely
      through the following signaling cascade: AMPAR activation -> ROS generation -> c
      Src phosphorylation -> NF-kappaB activation -> TNF-alpha elevation. The study
      suggests that AMPAR may participate in macrophage activation and inflammation. 

PMID- 25871801
TI  - Repeatability of Retinal Macular Thickness Measurements in Healthy Subjects and
      Diabetic Patients with Clinically Significant Macular Edema: Evaluation of the
      Follow-Up System of Spectralis Optical Coherence Tomography.
AB  - BACKGROUND: It was the aim of this study to compare the repeatability of
      Spectralis optical coherence tomography (OCT) retinal thickness measurements in
      healthy subjects and diabetic patients with clinically significant macular edema
      (CSME) with or without the use of the follow-up system. METHODS: Thirty-eight
      eyes of 38 healthy subjects (control group) and 68 eyes of 68 diabetic patients
      with CSME were included in the study. The coefficient of repeatability (CR) and
      intrasession coefficients of variation were tested with 20 * 15 degree raster
      scans consisting of 19 high-resolution line scans (15 frames per scan) that were
      repeated 3 times by 1 experienced examiner. The first scan was set as the
      reference scan, whereas the second and third scans were the follow-up scans and
      were performed with and without the use of the follow-up mode, respectively.
      RESULTS: The means and standard deviations for the central foveal subfield (CSF)
      in healthy subjects and diabetic patients were 289 +/- 21 and 402 +/- 105 MUm,
      respectively. Particularly in diabetic patients, examining the CSF, CR was 2.67%
      (10.73 um) and 6.73% (27.01 um) with and without using the follow-up mode,
      respectively, and the difference was statistically significant (p < 0.05).
      CONCLUSION: These results support the hypothesis that the follow-up system
      improves the repeatability either in healthy subjects or in diabetic patients
      with poor fixation. The wider improvement in repeatability in diabetic patients
      in the follow-up system group compared to the no follow-up system group are
      probably related to poor patient fixation or eye movement in patients with CSME.

PMID- 25871802
TI  - Developmental differences in intra-individual variability in children with ADHD
      and ASD.
AB  - BACKGROUND: Intra-individual variability reflects temporal variation within an
      individual's performance on a cognitive task. Children with developmental
      disorders, such as ADHD and ASD show increased levels of intra-individual
      variability. In typical development, intra-individual variability decreases
      sharply between the ages 6 and 20. The tight link between intra-individual
      variability and age has led to the suggestion that it may be marker of neural
      development. As there is accumulating evidence that ADHD and ASD are
      characterised by atypical neurodevelopmental trajectories, we set out to explore
      developmental changes in intra-individual variability in subjects with ADHD and
      ASD. METHOD: We used propensity score matching to match a cross-sectional sample
      of children with ADHD, ASD and control subjects (N = 405, aged 6-19 years old)
      for age, IQ and gender. We used ex-Gaussian distribution parameters to
      characterise intra-individual variability on fast responses (sigma) and slow
      responses (tau). RESULT: Results showed that there was a similar decrease in mean
      response times with age across groups, and an interaction between age and group
      for measures of variability, where there was a much lower rate of change in the
      variability parameters (sigma and tau) for subjects with ASD compared with the
      other two groups. Subjects with ADHD had higher intra-individual variability,
      reflected by both sigma and tau, but the rate of decrease in variability with age
      was similar to that of the controls. CONCLUSION: These results suggest that
      subjects with ADHD, ASD and controls differ in the rate at which intra-individual
      variability decreases during development, and support the idea that intra
      individual variability may be a marker of neural development, mimicking the
      neurodevelopmental changes in these disorders.

PMID- 25871804
TI  - Symmetry-derived half-metallicity in atomic and molecular junctions.
AB  - Achieving highly spin-polarized electric currents in atomic-scale junctions is of
      great importance in the field of nanoelectronics and spintronics. Based on robust
      symmetry considerations, we propose a mechanism to block completely one of spin
      conduction channels for a broad class of atomic and molecular junctions bridging
      two ferromagnetic electrodes. This particular behavior is due to the wave
      function orthogonality between spin up s-like states in ferromagnetic electrode
      and available pi channels in the junction. As a consequence, the system would
      ideally yield 100% spin-polarized current, with a junction acting thus as a "half
      metallic" conductor. Using ab initio electron transport calculations, we
      demonstrate this principle on two examples: (i) a short carbon chain and (ii) a
      pi-conjugated molecule (polythiophene) connected either to model semi-infinite Ni
      wires or to realistic Ni(111) electrodes. It is also predicted that such atomic
      scale junctions should lead to very high (ideally, infinite) magneto-resistance
      ratios since the electric current gets fully blocked if two electrodes have
      antiparallel magnetic alignment. 

PMID- 25871803
TI  - Prematurity, Opioid Exposure and Neonatal Pain: Do They Affect the Developing
      Brain?
AB  - BACKGROUND: Traditionally, 10 years ago, children born preterm often routinely
      received morphine, especially during mechanical ventilation. Studies in neonatal
      rats, whose stage of brain development roughly corresponds to that of children
      born preterm, found negative long-term effects after pain and opioid exposure.
      OBJECTIVES: We studied possible effects of prematurity, procedural pain and
      opioids in humans 10 years later. We hypothesized that these factors would
      negatively influence neurobiological, neuropsychological and sensory development
      later in life. METHODS: We included 19 children born preterm who as neonates
      participated in an RCT on the short-term effects of morphine administration and
      who previously participated in our follow-up studies at ages 5 and 8/9 years. We
      assessed associations between brain morphology (n = 11), neuropsychological
      functioning (n = 19) and thermal sensitivity (n = 17) and prematurity, opioid
      exposure and neonatal pain. RESULTS: Significant correlations (coefficients 0.60
      0.85) of gestational age, number of painful procedures and morphine exposure with
      brain volumes were observed. Significant correlations between these factors and
      thermal sensitivity were not established. Neuropsychological outcome was
      significantly moderately correlated with morphine exposure in only two subtests,
      and children performed in general 'average' by Dutch norms. CONCLUSIONS: Although
      prematurity, opioid exposure and neonatal pain were significantly associated with
      brain volume, no major associations with neuropsychological functioning or
      thermal sensitivity were detected. Our findings suggest that morphine
      administration during neonatal life does not affect neurocognitive performance or
      thermal sensitivity during childhood in children born preterm without brain
      damage during early life. Future studies with larger sample sizes are needed to
      confirm these findings.

PMID- 25871806
TI  - Pretreated baseline neutrophil count and chemotherapy-induced neutropenia may be
      conveniently available as prognostic biomarkers in advanced gastric cancer.
AB  - BACKGROUND: Increasing evidence suggests that neutrophils play a critical role in
      tumorigenesis, tumour cell proliferation and metastasis. The prognostic
      significance of such inflammation-associated markers has been explored in
      different cancers. AIM: To evaluate the prognostic effect of baseline neutrophil
      counts and nadir neutrophils on advanced gastric cancer (AGC) patients who were
      treated with two different chemotherapy regimens in our institution. METHODS:
      Data were collected retrospectively for 260 AGC patients treated between 1
      February 2009 and 31 December 2011. The prognostic effect of baseline neutrophil
      counts and nadir neutrophils on AGC patients was evaluated. RESULTS:
      Approximately 79% of the patients experienced neutropenia during chemotherapy.
      The median survival was 369 days for patients with neutrophil counts <=7.5 *
      10(9) /L and 326 days for patients with neutrophil counts >7.5 * 10(9) /L (P <
      0.001).The median survival was 340 days for patients with no neutropenia (grade
      0), 422 days for patients with mild neutropenia (grade 1-2) and 339 days for
      patients with severe neutropenia (grade 3-4) (P < 0.001).The adjusted hazard
      ratios (HR) for mild and severe neutropenia compared with absent neutropenia were
      0.572 (P = 0.002) and 1.246 (P = 0.219) respectively. Furthermore, it was
      suggested that pretreatment baseline neutrophil counts <=7.5 * 10(9) /L may be an
      independent predictor (HR = 0.683; P = 0.005). We also observed that other
      factors were independently associated with worse survival, such as higher
      performance status, stage IV and the presence of ascites. CONCLUSION: Our
      findings suggest that baseline neutrophil count and chemotherapy-induced
      neutropenia can be conveniently available as clinical biomarkers in AGC. Mild
      myelosuppression in patients with AGC most likely leads to better overall
      survival, whereas a high baseline neutrophil count may be associated with a worse
      prognosis.

PMID- 25871807
TI  - Determining the Ideal Strategy for Ventilator-associated Pneumonia Prevention.
      Cost-Benefit Analysis.
AB  - RATIONALE: Ventilator-associated pneumonia (VAP) is a common healthcare
      associated infection with high associated cost and poor patient outcomes. Many
      strategies for VAP reduction have been evaluated. However, the combination of
      strategies with the optimal cost-benefit ratio remains unknown. OBJECTIVES: To
      determine the preferred VAP prevention strategy, both from the hospital and
      societal perspectives. METHODS: A cost-benefit decision model with a Markov model
      was constructed. Baseline probability of VAP, death, reintubation, and discharge
      from the intensive care unit (ICU) alive were ascertained from clinical trial
      data. Model inputs were obtained from the medical literature and the U.S.
      Department of Labor; a device cost was obtained from the manufacturer.
      Sensitivity analyses were completed to test the robustness of model results.
      MEASUREMENTS AND MAIN RESULTS: Overall least expensive strategy and the strategy
      with the best cost-benefit ratio, up to a willingness to pay threshold of $50,000
      100,000 per case of VAP averted was sought. We examined a total of 120 unique
      combinations of VAP prevention strategies. The preferred strategy from the
      hospital perspective included subglottic suction endotracheal tubes, probiotics,
      and the Institute for Healthcare Improvement VAP Prevention Bundle. The preferred
      strategy from the point of view of society also included additional prevention
      measures (oral care with chlorhexidine and selective oral decontamination). No
      preferred strategies included silver endotracheal tubes or selective gut
      decontamination. CONCLUSIONS: Despite their infrequent use, current data suggest
      that the use of prophylactic probiotics and subglottic endotracheal tubes are
      cost-effective for preventing VAP from the societal and hospital perspectives.

PMID- 25871808
TI  - Measuring propargyl-linked drug populations inside bacterial cells, and their
      interaction with a dihydrofolate reductase target, by Raman microscopy.
AB  - We report the first Raman spectroscopic study of propargyl-linked dihydrofolate
      reductase (DHFR) inhibitors being taken up by wild type Escherichia coli,
      Klebsiella pneumoniae, and Staphylococcus aureus cells. A novel protocol is
      developed where cells are exposed to the fermentation medium containing a known
      amount of an inhibitor. At a chosen time point, the cells are centrifuged and
      washed to remove the extracellular compound, then frozen and freeze-dried. Raman
      difference spectra of the freeze-dried cells (cells exposed to the drug minus
      cells alone) provide spectra of the compounds inside the cells, where peak
      intensities allow us to quantify the number of inhibitors within each cell. A
      time course for the propargyl-linked DHFR inhibitor UCP 1038 soaking into E. coli
      cells showed that penetration occurs very quickly and reaches a plateau after 10
      min exposure to the inhibitor. After 10 min drug exposure, the populations of two
      inhibitors, UCP 1038 and UCP 1089, were ~1.5 * 10(6) molecules in each E. coli
      cell, ~4.7 * 10(5) molecules in each K. pneumonia cell, and ~2.7 * 10(6) in each
      S. aureus cell. This is the first in situ comparison of inhibitor population in
      Gram-negative and Gram-positive bacterial cells. The positions of the Raman peaks
      also reveal the protonation of diaminopyrimidine ring upon binding to DHFR inside
      cells. The spectroscopic signature of protonation was characterized by binding an
      inhibitor to a single crystal of DHFR.

PMID- 25871809
TI  - A concise synthetic route to the stereotetrad core of the briarane diterpenoids.
AB  - A concise synthesis (under 10 steps) of the stereotetrad core of the briarane
      diterpenoids is reported. This approach harnesses the unique reactivity of
      salicylate ester derived 2,5-cyclohexadienones to quickly build complexity. In
      particular, a highly diastereoselective acetylide conjugate addition/beta
      ketoester alkylation sequence was used to set the relative configuration of the
      C1 (quaternary) and C10 (tertiary) vicinal stereocenters. The sterochemical
      outcome of the beta-ketoester alkylation appears to be governed by torsional
      steering in the transition state. 

PMID- 25871810
TI  - Autophagic Markers BECLIN 1 and LC3 are Associated with Prognosis of Multiple
      Myeloma.
AB  - BACKGROUND/AIMS: Autophagy is crucial for the survival and function of plasma
      cells including protection from toxic misfolded immunoglobulin and proper energy
      metabolism. Multiple myeloma (MM) is an indolent but eventually fatal neoplasm of
      plasma cells. Autophagy may play a critical role in the survival of MM cells and
      their response to chemotherapeutic agents. In this study, we correlated the
      expression of autophagy-related proteins with the prognosis of MM. METHODS: In
      this retrospective cohort study, we examined the expression of the autophagic
      markers BECLIN 1 and microtubule-associated protein light chain 3 (LC3) in 89
      cases of MM biopsied from 2001 to 2004 at the Asan Medical Center. The
      association of the expression scores of these markers with clinical outcomes was
      assessed. RESULTS: Patients with strong immunoreactivity to BECLIN 1 or LC3 had a
      significantly better overall survival (OS) than patients with negative to
      moderate immunoreactivity (p = 0.036 and 0.018, respectively). This was also true
      for disease-specific survival (DSS; p = 0.051 and 0.043, respectively). In
      addition, LC3 immunostaining remained an independent factor impacting OS (p =
      0.028) and DSS (p = 0.020) after multivariate analysis. CONCLUSIONS: The results
      of this study suggest that higher immunoreactivity for autophagic markers in MM
      is associated with superior patient survival.

PMID- 25871812
TI  - On the virgin cleansing myth: gendered bodies, AIDS and ethnomedicine.
AB  - The belief that HIV/AIDS can be cured as a result of having sex with a virgin has
      been identified as a possible factor in the rape of babies and children in South
      Africa. While the prevalence of this myth has been a matter of concern in local
      communities for some time, there have been recent attempts to discern the extent
      to which this belief is exacerbating perceived increases in child rape and the
      rate of new HIV infections nationwide. This article attempts to reveal the
      systematic logic upon which is based the idea of 'virgin cleansing' as a
      therapeutic response to HIV/AIDS amongst the Zulu. Based on ethnographic research
      in several peri-urban settlements of KwaZulu-Natal province, key aspects of
      ethnomedical knowledge associated with notions of 'dirt' and women's bodies are
      examined along with the metaphors that inform local interpretations of HIV/AIDS.
      The author argues that closer attention paid to the shaping influence of cultural
      schemas are critical to better understanding belief-behaviour linkages in the
      context of rape and AIDS. 

PMID- 25871811
TI  - Gene-Gene Interactions Detection Using a Two-stage Model.
AB  - Genome-wide association studies (GWAS) have discovered numerous loci involved in
      genetic traits. Virtually all studies have reported associations between
      individual single nucleotide polymorphisms (SNPs) and traits. However, it is
      likely that complex traits are influenced by interaction of multiple SNPs. One
      approach to detect interactions of SNPs is the brute force approach which
      performs a pairwise association test between a trait and each pair of SNPs. The
      brute force approach is often computationally infeasible because of the large
      number of SNPs collected in current GWAS studies. We propose a two-stage model,
      Threshold-based Efficient Pairwise Association Approach (TEPAA), to reduce the
      number of tests needed while maintaining almost identical power to the brute
      force approach. In the first stage, our method performs the single marker test on
      all SNPs and selects a subset of SNPs that achieve a certain significance
      threshold. In the second stage, we perform a pairwise association test between
      traits and pairs of the SNPs selected from the first stage. The key insight of
      our approach is that we derive the joint distribution between the association
      statistics of a single SNP and the association statistics of pairs of SNPs. This
      joint distribution allows us to provide guarantees that the statistical power of
      our approach will closely approximate the brute force approach. We applied our
      approach to the Northern Finland Birth Cohort data and achieved 63 times speedup
      while maintaining 99% of the power of the brute force approach. 

PMID- 25871813
TI  - Assessment of behavioural risk factors for HIV/AIDS in selected target groups in
      and around Addis Ababa and Nazareth cities, Ethiopia.
AB  - A stratified cross-sectional survey was conducted on 2 278 people residing in and
      around Addis Ababa and Nazareth cities to assess the behavioural risk factors in
      HIV/AIDS in selected target groups from August 2000 to December 2000. The target
      groups, consisting of students, urban residents, farmers, and commercial sex
      workers, were interviewed using pre-tested questionnaires including indicators
      such as age, sex, educational and occupational status, sexual practice,
      preventive measures, condom use, etc. The findings revealed that 116 (32.6%) of
      the sex workers, 37 (21.5%) of the farmers, 33 (12%) of the students and 45
      (11.3%) of the urban residents had started sexual intercourse between the ages of
      13-15 years. The mean age at the time of sexual commencement for all respondents
      was 18.2 +/- 3.1 SD years. Among those who had already started sexual
      intercourse, 766 (63.7%) respondents had non-regular partners. Of the total
      respondents only 813 (36.2%) were using condoms while the remaining were opting
      for either abstinence (674 (30%)) or one-to-one sexual relationship (885 (39.4%))
      for prevention of HIV/AIDS. Ten (32.3%) of the farmers, 32 (19.8%) of the urban
      residents, 34 (17.5%) of the students and 33 (9.3%) of the sex workers were using
      condoms occasionally. The findings suggest that a well-coordinated campaign
      against the disease should be undertaken by targeting those who are at high risk.
      Condom use should also be promoted especially among the youth who seem to be
      engaged in sexual intercourse with multiple partners. 

PMID- 25871814
TI  - HIV/AIDS in South Africa: caring for vulnerable children.
AB  - South Africa currently has the fastest growing HIV/AIDS pandemic in the world.
      Efforts to manage the plight of children affected by HIV/AIDS have however been
      thwarted by two ubiquitous factors-poverty and inefficient state services.
      Caregivers, who are generally not public advocates for children's rights,
      disguise the state's negligence to respect, fulfill and protect children's
      rights. This paper suggests that the caring for HIV/AIDS affected children in
      South Africa needs to go beyond looking for willing and available members in the
      community to take on this responsibility. A developmental approach to addressing
      disparity, forming policies and implementing programmes could help in curtailing
      the effects of the pandemic. 

PMID- 25871815
TI  - Determinants of individual AIDS risk perception: knowledge, behavioural control
      and social influence.
AB  - In sub-Saharan Africa an almost universal awareness of the serious consequences
      of AIDS and of the sexual transmission of HIV co-exists together with a
      reluctance in adopting consequent preventive measures, in the form of protected
      sexual intercourse. The socio-psychological literature on health-related
      behaviour emphasises the perception of being at risk of HIV infection as being
      one of the necessary conditions for preventive behaviour to be adopted. Analysing
      data from the Kenya Diffusion and Ideational Change (KDIC) Project, this paper
      investigates the determinants of the reported degree of risk perception of
      getting infected by HIV. In particular, adopting a social interaction approach,
      we argue that individual risk perception is shaped by social network influences.
      We use information on ego-centred networks in which individuals are involved in
      conversations about the risk of getting infected by HIV. We are able to show that
      the importance of AIDS related knowledge and behavioural factors risks to be mis
      estimated if one neglects the role of individuals' reciprocal influences. We
      conclude that risk perception is as much a product of individual characteristics
      and behaviour as it is a collective feeling shared among interacting individuals.
      Results suggest that in our study men are more susceptible than women to network
      influence. 

PMID- 25871816
TI  - AIDS, individual behaviour and the unexplained remaining variation.
AB  - From the start of the AIDS pandemic, individual behaviour has been put forward,
      implicitly or explicitly, as the main explanatory concept for understanding the
      epidemiology of HIV infection and in particular for the rapid spread and high
      prevalence in sub-Saharan Africa. This has had enormous implications for the
      international response to AIDS and has heavily influenced public health policy
      and strategy and the design of prevention and care interventions at national,
      community and individual level. It is argued that individual behaviour alone
      cannot possibly account for the enormous variation in HIV prevalence between
      population groups, countries and regions and that the unexplained remaining
      variation has been neglected by the international AIDS community. Biological
      vulnerability to HIV due to seriously deficient immune systems has been ignored
      as a determinant of the high levels of infection in certain populations. This is
      in sharp contrast to well proven public health approaches to other infectious
      diseases. In particular, it is argued that poor nutrition and co-infection with
      the myriad of other diseases of poverty including tuberculosis, malaria,
      leishmaniasis and parasitic infections, have been neglected as root causes of
      susceptibility, infectiousness and high rates of transmission of HIV at the level
      of populations. Vulnerability in terms of non-biological factors such as labour
      migration, prostitution, exchange of sex for survival, population movements due
      to war and violence, has received some attention but the solutions proposed to
      these problems are also inappropriately focused on individual behaviour and
      suffer from the same neglect of economic and political root causes. As the
      foundation for the international community's response to the AIDS pandemic,
      explanations of HIV/AIDS epidemiology in terms of individual behaviour are not
      only grossly inadequate, they are highly stigmatising and may in some cases, be
      racist. They have diverted attention from poverty and powerlessness as root
      causes of vulnerability to infection and as such they are a waste of scarce
      resources. A return to a basic needs approach to all the diseases of poverty is
      nothing more than proven public health wisdom and experience. A sustainable and
      meaningful response to AIDS is simultaneously a sustainable and meaningful
      response to all the diseases of poverty. The obstacles to the adoption of this
      approach are economic and political and must be confronted at the level of
      international financial institutions, the globalisation of neoliberal economic
      systems, the growing power imbalances between and within nations and the
      undermining of democracy and national sovereignty. An alternative strategy for
      AIDS and the other diseases of poverty would build on macroeconomic reforms for a
      fair, rational and sustainable international economic order so that
      democratically elected governments may meet their people's basic needs, including
      health, without external interference. 

PMID- 25871817
TI  - Preventing HIV infections in children and adolescents in sub-Saharan Africa
      through integrated care and support activities: a review of the literature.
AB  - Sub-Saharan Africa has been hit harder by the HIV/AIDS pandemic than any other
      region of the world, and children under age eighteen represent one-third of all
      new HIV infections occurring there annually. While HIV prevention efforts
      targeting youth are well established, few prevention programmes provide
      comprehensive care and support services. One reason for this is that prevention
      messages are often targeted only at older adolescents, and care and support
      activities typically emphasise the needs of younger children. By expanding
      prevention activities to younger children, and expanding care and support
      activities to older adolescents, more holisitic, and truly integrated programmes
      can be developed which address the common factors which make children of any age
      particularly vulnerable to HIV infection, namely: inadequate access to health
      care and unstable familial and social environments. This paper reviews evidence
      of the potential impact of care and support activities on HIV prevention among
      youth, and presents a conceptual framework for the development of comprehensive,
      effective, integrated HIV/AIDS prevention and care programmes tailored to the
      specific needs of youth. 

PMID- 25871818
TI  - Effect of mixing, concentration and temperature on the formation of
      mesostructured solutions and their role in the nucleation of DL-valine crystals.
AB  - We report investigations on the formation of mesostructured solutions in DL
      valine-water-2-propanol mixtures, and the crystallization of DL-valine from these
      solutions. Mesostructured liquid phases, similar to those previously observed in
      aqueous solutions of glycine and DL-alanine, were observed using Dynamic Light
      Scattering and Brownian microscopy, in both undersaturated and supersaturated
      solutions below a certain transition temperature. Careful experimentation was
      used to demonstrate that the optically clear mesostructured liquid phase,
      comprising colloidal mesoscale clusters dispersed within bulk solution, is
      thermodynamically stable and present in equilibrium with the solid phase at
      saturation conditions. Solutions prepared by slow cooling contained mesoscale
      clusters with a narrow size distribution and a mean hydrodynamic diameter of
      around 200 nm. Solutions of identical composition prepared by rapid isothermal
      mixing of valine aqueous solutions with 2-propanol contained mesoscale clusters
      which were significantly larger than those observed in slowly cooled solutions.
      The presence of larger mesoscale clusters was found to correspond to faster
      nucleation. Observed induction times were strongly dependent on the rapid initial
      mixing step, although solutions were left undisturbed afterwards and the
      induction times observed were up to two orders of magnitude longer than the
      initial mixing period. We propose that mesoscale clusters above a certain
      critical size are likely to be the location of productive nucleation events.

PMID- 25871819
TI  - Prescription opioid abuse: Problems and responses.
AB  - Prescription opioid abuse and addiction, along with consequences such as overdose
      death and increasing transition to heroin use, constitute a devastating public
      health problem in the United States. Increasingly it is clear that
      overprescription of these medications over the past two decades has been a major
      upstream driver of the opioid abuse epidemic. This commentary considers the
      factors that have led to overprescription of opioids by clinicians, discusses
      recent evidence casting doubt on the efficacy of opioids for treating chronic
      pain, and describes the ongoing efforts by federal and community stakeholders to
      address this epidemic-for example, supporting prescription drug monitoring
      programs and improved clinician training in pain management to help reduce the
      supply of opioids, increasing dissemination of evidence-based primary prevention
      programs to reduce demand for opioids, and expanding access to effective opioid
      agonist therapies and antagonist medications for both treatment and overdose
      prevention. 

PMID- 25871820
TI  - Infrared photodissociation spectroscopy of mass-selected heteronuclear iron
      copper carbonyl cluster anions in the gas phase.
AB  - Mass-selected heteronuclear iron-copper carbonyl cluster anions CuFe(CO)n(-) (n =
      4-7) are studied by infrared photodissociation spectroscopy in the carbonyl
      stretching frequency region in the gas phase. The cluster anions are produced via
      a laser vaporization supersonic cluster ion source. Their geometric structures
      are determined by comparison of the experimental spectra with those calculated by
      density functional theory. The experimentally observed CuFe(CO)n(-) (n = 4-7)
      cluster anions are characterized to have (OC)4Fe-Cu(CO)n-4 structures, each
      involving a C3v symmetry Fe(CO)4(-) building block. Bonding analysis indicates
      that the Fe-Cu bond in the CuFe(CO)n(-) (n = 4-7) cluster anions is a sigma type
      single bond with the iron center possessing the most favored 18-electron
      configuration. The results provide important new insight into the structure and
      bonding of hetronuclear transition metal carbonyl cluster anions. 

PMID- 25871821
TI  - A new insight into the molecular mechanism of atrial fibrillation: the role of
      microRNAs.

PMID- 25871822
TI  - Dose-dependent effects on sphingoid bases and cytokines in chickens fed diets
      prepared with fusarium verticillioides culture material containing fumonisins.
AB  - In chickens, the effect of mycotoxins, especially fumonisins (FB), in the
      gastrointestinal tract (GIT) is not well documented. Thus, this study in broiler
      chicks determined the effects of consuming diets prepared with Fusarium
      verticillioides culture material containing FB on intestinal gene expression and
      on the sphinganine (Sa)/sphingosine (So) ratio (Sa/So; a biomarker of FB effect
      due to disruption of sphingolipid metabolism). Male broilers were assigned to 6
      diets (6 cages/diet; 6 birds/cage) from hatch to 20 days containing 0.4, 5.6,
      11.3, 17.5, 47.8, or 104.8 mg FB/kg diet. Exposure to FB altered the Sa/So ratio
      in all tissues analyzed, albeit to varying extents. Linear dose-responses were
      observed in the kidney, jejunum and cecum. The liver and the ileum were very
      sensitive and data fit a cubic and quadratic polynomial model, respectively. Gene
      expression in the small intestine revealed low but significant upregulations of
      cytokines involved in the pro-inflammatory, Th1/Th17 and Treg responses,
      especially at 10 days of age. Interestingly, the cecal tonsils exhibited a
      biphasic response. Unlike the sphingolipid analysis, the effects seen on gene
      expression were not dose dependent, even showing more effects when birds were
      exposed to 11.3 mg FB/kg. In conclusion, this is the first report on the
      disruption of the sphingolipid metabolism by FB in the GIT of poultry. Further
      studies are needed to reach conclusions on the biological meaning of the
      immunomodulation observed in the GIT, but the susceptibility of chickens to
      intestinal pathogens when exposed to FB, at doses lower than those that would
      cause overt clinical symptoms, should be addressed.

PMID- 25871824
TI  - The logic of automated glycan assembly.
AB  - Carbohydrates are the most abundant biopolymers on earth and part of every living
      creature. Glycans are essential as materials for nutrition and for information
      transfer in biological processes. To date, in few cases a detailed correlation
      between glycan structure and glycan function has been established. A molecular
      understanding of glycan function will require pure glycans for biological,
      immunological, and structural studies. Given the immense structural complexity of
      glycans found in living organisms and the lack of amplification methods or
      expression systems, chemical synthesis is the only means to access usable
      quantities of pure glycan molecules. While the solid-phase synthesis of DNA and
      peptides has become routine for decades, access to glycans has been technically
      difficult, time-consuming and confined to a few expert laboratories. In this
      Account, the development of a comprehensive approach to the automated synthesis
      of all classes of mammalian glycans, including glycosaminoglycans and
      glycosylphosphatidyl inositol (GPI) anchors, as well as bacterial and plant
      carbohydrates is described. A conceptual advance concerning the logic of glycan
      assembly was required in order to enable automated execution of the synthetic
      process. Based on the central glycosidic bond forming reaction, a general concept
      for the protecting groups and leaving groups has been developed. Building blocks
      that can be procured on large scale, are stable for prolonged periods of time,
      but upon activation result in high yields and selectivities were identified. A
      coupling-capping and deprotection cycle was invented that can be executed by an
      automated synthesis instrument. Straightforward postsynthetic protocols for
      cleavage from the solid support as well as purification of conjugation-ready
      oligosaccharides have been established. Introduction of methods to install
      selectively a wide variety of glycosidic linkages has enabled the rapid assembly
      of linear and branched oligo- and polysaccharides as large as 30-mers. Fast,
      reliable access to defined glycans that are ready for conjugation has given rise
      to glycan arrays, glycan probes, and synthetic glycoconjugate vaccines. While an
      ever increasing variety of glycans are accessible by automated synthesis, further
      methodological advances in carbohydrate chemistry are needed to make all possible
      glycans found in nature. These tools begin to fundamentally impact the medical
      but also materials aspects of the glycosciences. 

PMID- 25871823
TI  - ET-1 Induced Downregulation of MRP2 via miRNA 133a - A Marker for Tubular
      Nephrotoxicity?
AB  - BACKGROUND: Multiple drug resistance (MDR), known from treating malignant tumors
      with chemotherapy, increases the efflux of reabsorbed reagents in tumor cells.
      This mechanism has been reported in the renal proximal tubule and may prevent
      therapeutic tubular protection in proteinuria. Since endothelin-1 (ET-1), a major
      component in the urine of proteinuric patients, stimulates proximal tubules, its
      influence on MDR was analyzed with emphasis on the multidrug resistance
      associated protein 2 (MRP2), a prominent transporter in the human proximal tubule
      and microRNA (miRNA) 133a. METHODS: ET-1 stimulated, cultured human renal
      proximal tubule cells (RPTECs), were analyzed via Western blot for the expression
      of MRP2 and via qRT-PCR for miRNA 133a. For direct interaction between the miRNA
      133a and the 3'UTR of MRP2, an immunoprecipitation was performed using FITC
      labelled miRNA 133a as capture, followed by MRP2 PCR analysis and Sanger
      sequencing. Murine Adriamycin nephropathic model and human proteinuric samples
      showed high levels of miRNA 133a but low levels of MRP2. The increasing miRNA
      133a levels were detectable in urine samples of humans and animals. RESULTS: ET-1
      activates the miRNA 133a, which can bind to the 3'UTR of MRP2 and is therefore
      responsible for the detectable decrease of MRP2. CONCLUSION: This is the first
      report to analyze the correlation between ET-1-induced miRNA 133a overexpression
      in proteinuria resulting in MRP2 downregulation, which is a contributing factor
      for renal cytotoxicity. The detection of the miRNA 133a in urine samples can be
      possibly used as a monitor for cytotoxicity.

PMID- 25871826
TI  - Adenoviral vector-mediated overexpression of osteoprotegerin accelerates
      osteointegration of titanium implants in ovariectomized rats.
AB  - This study investigated the efficacy of human osteoprotegerin (hOPG) transgene to
      accelerate osteointegration of titanium implant in ovariectomized (OVX) rats.
      Bone marrow stromal cells transduced with Ad-hOPG-EGFP could sustainedly express
      hOPG. Osteoclast precursor RAW264.7 cells treated by the hOPG were examined by
      tartrate-resistant acid phosphatase (TRAP) staining and bone slice resorption
      assay. The results showed differentiation and function of osteoclasts were
      significantly suppressed by hOPG in vitro. Ad-hOPG-EGFP was locally administered
      to the bone defect prior to implant placement in OVX and sham rats. After 3, 7,
      28 days of implantation, the femurs were harvested for molecular and histological
      analyses. Successful transgene expression was confirmed by western blot and
      cryosectioning. A significant reduction in TRAP+ numbers was detected in Ad-hOPG
      EGFP group. Real-time reverse transcriptase-PCR examination revealed that hOPG
      transgene markedly diminished the expression of cathepsin K and receptor
      activator for nuclear factor-kappa B ligand in vivo. The transgene hOPG
      modification revealed a marked increasing osteointegration and restored implant
      stability in OVX rats (P<0.01), compared with the control groups (Ad-EGFP or
      sterilized phosphate-buffered saline) 28 days after implantation. In conclusion,
      hOPG via direct adenovirus-mediated gene transfer could accelerate
      osteointegration of titanium implants in OVX rats. Osteoprotegerin gene therapy
      may be an effective strategy to osteointegration of implants under osteoporotic
      conditions. 

PMID- 25871825
TI  - Macrophage-specific overexpression of interleukin-5 attenuates atherosclerosis in
      LDL receptor-deficient mice.
AB  - Interleukin-5 (IL-5) increases the secretion of natural T15/EO6 IgM antibodies
      that inhibit the uptake of oxidized low-density lipoprotein (LDL) by macrophages.
      This study aimed to determine whether macrophage-specific expression of IL-5 in
      LDL receptor-deficient mice (Ldlr(-/-)) could improve cholesterol metabolism and
      reduce atherosclerosis. To induce macrophage-specific IL-5 expression, the
      pLVCD68-IL5 lentivirus was delivered into Ldlr(-/-) mice via bone marrow
      transplantation. The recipient mice were fed a Western-type diet for 12 weeks to
      induce lesion formation. We found that IL-5 was efficiently and specifically
      overexpressed in macrophages in recipients of pLVCD68-IL5-transduced bone marrow
      cells (BMC). Plasma titers of T15/EO6 IgM antibodies were significantly elevated
      by 58% compared with control mice transplanted with pLVCD68 lacking the IL-5
      coding sequence. Plaque areas of aortas in IL-5-overexpressing mice were reduced
      by 43% and associated with a 2.4-fold decrease in lesion size at the aortic roots
      when compared with mice receiving pLVCD68-transduced BMCs. The study showed that
      macrophage-specific overexpression of IL-5 inhibited the progression of
      atherosclerotic lesions. These findings suggest that modulation of IL-5 cytokine
      expression represents a potential strategy for intervention of familial
      hypercholesterolemia and other cardiovascular diseases. 

PMID- 25871827
TI  - Preclinical safety and tolerability of a repeatedly administered human
      leishmaniasis DNA vaccine.
AB  - The leishmaniases are a complex of vector-borne diseases caused by protozoan
      parasites of the genus Leishmania. LEISHDNAVAX is a multi-antigen, T-cell epitope
      enriched DNA vaccine candidate against human leishmaniasis. The vaccine candidate
      has been proven immunogenic and showed prophylactic efficacy in preclinical
      studies. Here, we describe the safety testing of LEISHDNAVAX in naive mice and
      rats, complemented by the demonstration of tolerability in Leishmania-infected
      mice. Biodistribution and persistence were examined following single and repeated
      intradermal (i.d.) administration to rats. DNA vectors were distributed
      systemically but did not accumulate upon repeated injections. Although vector DNA
      was cleared from most other tissues within 60 days after the last injection, it
      persisted in skin at the site of injection and in draining lymph nodes.
      Evaluation of single-dose and repeated-dose toxicity of the vaccine candidate
      after i.d. administration to naive, non-infected mice did not reveal any safety
      concerns. LEISHDNAVAX was also well tolerated in Leishmania-infected mice. Taken
      together, our results substantiate a favorable safety profile of LEISHDNAVAX in
      both naive and infected animals and thus, support the initiation of clinical
      trials for both preventive and therapeutic applications of the vaccine. 

PMID- 25871828
TI  - Ultrasound-assisted nonviral gene transfer of AQP1 to the irradiated minipig
      parotid gland restores fluid secretion.
AB  - Xerostomia is a common side effect of ionizing radiation used to treat head and
      neck cancer. A groundbreaking Phase I human clinical trial using Adenoviral gene
      transfer of Aquaporin-1 (AQP1) to a single salivary gland of individuals
      suffering from radiation-induced xerostomia has recently been reported.
      Unfortunately, the limitations of the Adenoviral vector system used in this
      pioneering trial preclude its advancement to a Phase II trial, and we have thus
      undertaken to evaluate the therapeutic potential of ultrasound-assisted nonviral
      gene transfer (UAGT) as an alternative means of delivering AQP1 gene therapy to
      the salivary gland by comparing head-to-head with the canonical Adenoviral vector
      in a swine model. Swine irradiated unilaterally with a 10-Gy electron beam
      targeted at the parotid gland suffered from significant, sustained hyposalivation
      that was bilateral, despite irradiation being confined to the targeted gland.
      Unilateral AQP1 gene therapy with UAGT resulted in bilateral restoration of
      stimulated salivary flow at 48 h and 1 week post treatment (1.62+/-0.48 ml and
      1.87+/-0.45 ml) to preinjury levels (1.34+/-0.14 ml) in a manner comparable to
      Adenoviral delivery (2.32+/-0.6 ml and 1.33+/-0.97 ml). UAGT can replace the
      Adenoviral vector as a means of delivering AQP1 gene therapy in the irradiated
      swine model, and it is a candidate for advancement to a Phase I human clinical
      trial. 

PMID- 25871829
TI  - Increased LDL electronegativity in chronic kidney disease disrupts calcium
      homeostasis resulting in cardiac dysfunction.
AB  - Chronic kidney disease (CKD), an independent risk factor for cardiovascular
      disease, is associated with abnormal lipoprotein metabolism. We examined whether
      electronegative low-density lipoprotein (LDL) is mechanistically linked to
      cardiac dysfunction in patients with early CKD. We compared echocardiographic
      parameters between patients with stage 2 CKD (n = 88) and normal controls (n =
      89) and found that impaired relaxation was more common in CKD patients. Reduction
      in estimated glomerular filtration rate was an independent predictor of left
      ventricular relaxation dysfunction. We then examined cardiac function in a rat
      model of early CKD induced by unilateral nephrectomy (UNx) by analyzing pressure
      volume loop data. The time constant of isovolumic pressure decay was longer and
      the maximal velocity of pressure fall was slower in UNx rats than in controls.
      When we investigated the mechanisms underlying relaxation dysfunction, we found
      that LDL from CKD patients and UNx rats was more electronegative than LDL from
      their respective controls and that LDL from UNx rats induced intracellular
      calcium overload in H9c2 cardiomyocytes in vitro. Furthermore, chronic
      administration of electronegative LDL, which signals through lectin-like oxidized
      LDL receptor-1 (LOX-1), induced relaxation dysfunction in wild-type but not LOX
      1(-/-) mice. In in vitro and in vivo experiments, impaired cardiac relaxation was
      associated with increased calcium transient resulting from nitric oxide (NO)
      dependent nitrosylation of SERCA2a due to increases in inducible NO synthase
      expression and endothelial NO synthase uncoupling. In conclusion, LDL becomes
      more electronegative in early CKD. This change disrupts SERCA2a-regulated calcium
      homeostasis, which may be the mechanism underlying cardiorenal syndrome.

PMID- 25871830
TI  - Inhibition of myocardial reperfusion injury by ischemic postconditioning requires
      sirtuin 3-mediated deacetylation of cyclophilin D.
AB  - RATIONALE: How ischemic postconditioning can inhibit opening of the mitochondrial
      permeability transition pore (PTP) and subsequent cardiac myocytes death at
      reperfusion remains unknown. Recent studies have suggested that de-acetylation of
      cyclophilin D (CyPD) by sirtuin 3 (SIRT3) can modulate its binding to the PTP.
      OBJECTIVE: The aim of the present study was to examine whether ischemic
      postconditioning (PostC) might activate SIRT3 and consequently prevent lethal
      myocardial reperfusion injury through a deacetylation of CyPD. METHODS AND
      RESULTS: Using hypoxia-reoxygenation (H/R) in H9C2 cells, we showed that SIRT3
      overexpression prevented CyPD acetylation, limited PTP opening and reduced cell
      death by 24%. In vitro modification of the CyPD acetylation status in MEFs by
      site-directed mutagenesis altered capacity of PTP opening by calcium. Calcium
      Retention Capacity (CRC) was significantly decreased with CyPD-KQ that mimics
      acetylated protein compared with CyPD WT (871 +/- 266 vs 1193 +/- 263 nmoles
      Ca(2+)/mg protein respectively). Cells expressing non-acetylable CyPD mutant
      (CyPD-KR) displayed 20% decrease in cell death compared to cells expressing CyPD
      WT after H/R. Correspondingly, in mice we showed that cardiac ischemic
      postconditioning could not reduce infarct size and CyPD acetylation in SIRT3 KO
      mice, and was unable to restore CRC in mitochondria as it is observed in WT mice.
      CONCLUSIONS: Our study suggests that the increased acetylation of CyPD following
      myocardial ischemia-reperfusion facilitates PTP opening and subsequent cell
      death. Therefore ischemic postconditioning might prevent lethal reperfusion
      injury through an increased SIRT3 activity and subsequent attenuation of CyPD
      acetylation at reperfusion.

PMID- 25871832
TI  - Experimental Validation of the Sensitivity of Waveguide Grating Based
      Refractometric (Bio)sensors.
AB  - Despite the fact that the theoretical foundations of the sensitivity of waveguide
      grating based (bio)sensors are well-known, understood and their implications
      anticipated by the scientific community since several decades, to our knowledge,
      no prior publication has experimentally confirmed waveguide sensitivity for
      multiple film thicknesses, wavelengths and polarization of the propagating light.
      In this paper, the bulk refractive index sensitivity versus waveguide thickness
      of said refractometric sensors is experimentally determined and compared with
      predictions based on established theory. The effective refractive indices and the
      corresponding sensitivity were determined via the sensors' coupling angles at
      different cover refractive indices for transverse electric as well as transverse
      magnetic polarized illumination at various wavelengths in the visible and near
      infrared. The theoretical sensitivity was calculated by solving the mode equation
      for a three layer waveguide. 

PMID- 25871831
TI  - NOTCH1 regulates matrix gla protein and calcification gene networks in human
      valve endothelium.
AB  - Valvular and vascular calcification are common causes of cardiovascular morbidity
      and mortality. Developing effective treatments requires understanding the
      molecular underpinnings of these processes. Shear stress is thought to play a
      role in inhibiting calcification. Furthermore, NOTCH1 regulates vascular and
      valvular endothelium, and human mutations in NOTCH1 can cause calcific aortic
      valve disease. Here, we determined the genome-wide impact of altering shear
      stress and NOTCH signaling on human aortic valve endothelium. mRNA-sequencing of
      primary human aortic valve endothelial cells (HAVECs) with or without knockdown
      of NOTCH1, in the presence or absence of shear stress, revealed NOTCH1-dependency
      of the atherosclerosis-related gene connexin 40 (GJA5), and numerous repressors
      of endochondral ossification. Among these, matrix gla protein (MGP) is highly
      expressed in aortic valve and vasculature, and inhibits soft tissue calcification
      by sequestering bone morphogenetic proteins (BMPs). Altering NOTCH1 levels
      affected MGP mRNA and protein in HAVECs. Furthermore, shear stress activated
      NOTCH signaling and MGP in a NOTCH1-dependent manner. NOTCH1 positively regulated
      endothelial MGP in vivo through specific binding motifs upstream of MGP. Our
      studies suggest that shear stress activates NOTCH1 in primary human aortic valve
      endothelial cells leading to downregulation of osteoblast-like gene networks that
      play a role in tissue calcification. 

PMID- 25871833
TI  - Production of EPS under Cr(VI) challenge in two indigenous bacteria isolated from
      a tannery effluent.
AB  - Indigenous Cr(VI) reducing bacterial strains Pseudomonas aeruginosa Rb-1 and
      Ochrobactrum intermedium Rb-2 were evaluated for EPS production under Cr(VI)
      challenged and free conditions. Strain Rb-2 was more efficient in total EPS
      production (13.63 mg g(-1)) than Rb-1 (4.15 mg g(-1)) under Cr(VI) stress. Thick
      covering of capsular material around the cells of both bacterial strains was
      detected by electron microscopy. Transmission electron micrographs showed the
      appearance of pilli like structures under chromium stress by two bacteria
      suggested the possible involvement of this in exchange of hereditary material to
      increase their chances of survival under stress conditions. FTIR study showed
      involvement of sulphonate and hydroxyl groups in the binding with Cr(VI) ions.
      Solid-state (13) C NMR spectra revealed that EPS produced by both strains
      exhibited structural similarity with the glucan. The partial psl gene sequences
      of Rb-1 and Rb-2 showed homology with psl gene of Pseudomonas aeruginosa PAO1 and
      capsular polysaccharide biosynthesis protein of various strains of Pseudomonas.
      This is the first report on the identification of psl gene from Ochrobacterum in
      NCBI GenBank database up to our knowledge.

PMID- 25871835
TI  - An NHC-Stabilized Silicon Analogue of Acylium Ion: Synthesis, Structure,
      Reactivity, and Theoretical Studies.
AB  - The silicon analogues of an acylium ion, namely, sila-acylium ions 2a and 2b
      [RSi(O)(NHC)2]Cl stabilized by two N-heterocyclic carbenes (NHC = 1,3,4,5
      tetramethylimidazol-2-ylidene), and having chloride as a countercation were
      successfully synthesized by the reduction of CO2 using the donor stabilized
      silyliumylidene cations 1a and 1b [RSi(NHC)2]Cl (1a, 2a; R = m-Ter = 2,6
      Mes2C6H3, Mes = 2,4,6-Me3C6H2 and 1b, 2b; R = Tipp = 2,4,6-iPr3C6H2).
      Structurally, compound 2a features a four coordinate silicon center together with
      a double bond between silicon and oxygen atoms. The reaction of sila-acylium ions
      2a and 2b with water afforded different products which depend on the bulkiness of
      aryl substituents. Although the exposure of 2a to H2O afforded a stable silicon
      analogue of carboxylate anion as a dimer form, [m-TerSi(O)O]2(2-).2[NHC-H](+)
      (3), the same reaction with the less bulkier triisopropylphenyl substituted sila
      acylium ion 2b afforded cyclotetrasiloxanediol dianion [{TippSi(O)}4{(O)OH}2](2
      ).2[NHC-H](+) (4). Metric and DFT (Density Functional Theory) evidence support
      that 2a and 2b possess strong Si?O double bond character, while 3 and 4 contain
      more ionic terminal Si-O bonds. Mechanistic details of the formation of different
      (SiO)n (n = 2, 3, 4) core rings were explored using DFT to explain the
      experimentally characterized products and a proposed stable intermediate was
      identified with mass spectrometry. 

PMID- 25871834
TI  - An overview of biological production of L-theanine.
AB  - L-Theanine (gamma-glutamylethylamide) is a unique non-protein amino acid that is
      naturally found in tea plants. It contributes to the umami taste and unique
      flavor to green tea infusion, and thus its content in tea leaves highly impacts
      the tea quality and price. In addition to the graceful taste, it has been proved
      to have many beneficial physiological effects, especially promoting relaxation
      and improving concentration and learning ability. Based on these promising
      advantages, L-theanine has been commercially developed as a valuable ingredient
      for use in food and beverages to improve and/or maintain human health. L-Theanine
      can be obtained by chemical synthesis or isolation from tea, while chemical
      synthesis of L-theanine is hard to be accepted by consumers and is not allowed to
      use in food industry, and isolation of L-theanine in high purity generally
      involves time-consuming, cost-ineffective, and complicated operational processes.
      Accordingly, the biological production of L-theanine has recently attracted much
      attention. Four kinds of bacterial enzymes, including L-glutamine synthetase,
      gamma-glutamylmethylamide synthetase, gamma-glutamyltranspeptidase, and L
      glutaminase, have been characterized to have L-theanine-producing ability.
      Herein, an overview of recent studies on the biological production of L-theanine
      was presented. 

PMID- 25871836
TI  - Clinical and instrumental evaluation of the efficacy of a new depigmenting agent
      containing a combination of a retinoid, a phenolic agent and an antioxidant for
      the treatment of solar lentigines.
AB  - BACKGROUND: Solar lentigines are common benign macular hyperpigmented lesions
      localized on sun-exposed areas. OBJECTIVE: To evaluate the efficacy and safety of
      a new depigmenting agent containing a retinoid (retinaldehyde), a new phenolic
      agent (4-(1-phenylethyl)-resorcinol) and a reducing agent (delta-tocopheryl-beta
      D-glucopyranoside) in the topical treatment of solar lentigines. PATIENTS AND
      METHODS: Twenty patients with solar lentigines of the face and hands applied the
      depigmenting agent on each lentigo once daily for 12 weeks. The outcome was
      evaluated at 45 days (T1) and 3 months (T2) after the end of treatment compared
      to baseline (T0) by means of clinical evaluation, Mexameter(r) and Visioface
      devices for digital and ultraviolet computerized image analysis of skin color as
      well as in vivo reflectance confocal microscopy. RESULTS: Image analysis and
      confocal laser reflectance microscopy showed that hyperpigmentation was
      significantly reduced at T2 compared to baseline and to controls. CONCLUSION: The
      study treatment was well tolerated and showed significant improvement in the
      depigmentation of solar lentigines.

PMID- 25871837
TI  - Radioguided occult lesion localisation using iodine-125 seeds ('ROLLIS') for
      removal of impalpable breast lesions: First Australian experience.
AB  - INTRODUCTION: Approximately one-third of breast cancers are impalpable and
      require pre-operative image-guided localisation. Hook-wire localisation (HWL) is
      commonly used but has several disadvantages. Use of a low-activity radioactive
      iodine-125 seed is a promising alternative technique used in the USA and the
      Netherlands. This pilot study describes the first use of this in Australia.
      METHODS: In this prospective pilot study, 21 participants with biopsy-proven
      breast cancer underwent radioguided occult lesion localisation using iodine-125
      seed(s) (ROLLIS) with insertion of a hook-wire for back up. Sentinel node biopsy
      was performed where indicated. Ease of hook-wire and seed insertion, duration of
      the procedure, dependence on the seed versus hook-wire during surgery, lesion
      location within the specimen, histopathology including size of radial margins,
      the ease of seed retrieval in pathology, and safe return of seeds for disposal
      were documented. Radiation dosimetry of staff was performed. RESULTS: All seeds
      were placed within 3.5 mm of the lesion. All lesions and seeds were removed. One
      participant needed re-excision for involved margins. Radiologists and surgeons
      both preferred ROLLIS. Surgeons were able to depend on the seed for localisation
      in all but one case. Sentinel node biopsy was successfully performed when
      required. Pathologists found seed retrieval quick and easy, with no detrimental
      effect on tissue processing. No radiation doses measurably above background were
      received by staff. CONCLUSION: ROLLIS is an easily learnt, safe and effective
      alternative technique to standard HWL.

PMID- 25871838
TI  - Differential Gene Expression in Diabetic Nephropathy in Individuals With Type 1
      Diabetes.
AB  - CONTEXT: Diabetic nephropathy (DN) is the leading cause of end-stage renal
      disease (ESRD) in the United States. OBJECTIVE: The aim of this study was to
      determine whether there were skin fibroblast gene expression differences between
      subjects with type 1 diabetes (T1D) with or without DN. SETTING: This was a cross
      sectional study conducted in the University of Minnesota. PATIENTS: Study
      volunteers were 100 former participants of Genetics of Kidneys in Diabetes: 40
      were diabetic nephropathy (DN) Controls, normoalbuminuric after >= 15 years of
      T1D; and 60 were DN Cases, 25 with proteinuria and 35 with ESRD. INTERVENTION(S):
      Skin fibroblasts were grown in high glucose (HG) for five passages (approximately
      6 weeks). MAIN OUTCOME MEASURE(S): SF gene expression was assessed by
      transcriptome sequencing using the Illumina HiSeq 2000 platform. Pathway analyses
      tested directionally consistent group differences within the Kyoto Encyclopedia
      of Genes and Genomes pathways. RESULTS: Eight pathways, all related to cell cycle
      and repair, were up-regulated in the DN Controls vs the DN Cases. These pathways
      markedly overlapped with the pathways up-regulated by HG in T1D monozygotic twins
      (MZT), but not in their non-T1D MZT. DN Cases showed statistical trends toward up
      regulation of these pathways vs non-T1D MZT, but much less so than the DN
      Controls. CONCLUSIONS: Together, these data suggest that SF from T1D patients
      undergo epigenetic modifications resulting in increased expression of genes in
      healing and repair pathways. These responses, much more robust in patients
      protected from DN, suggest that epigenetic factors are important in DN risk.

PMID- 25871839
TI  - Novel Lethal Form of Congenital Hypopituitarism Associated With the First
      Recessive LHX4 Mutation.
AB  - BACKGROUND: LHX4 encodes a member of the LIM-homeodomain family of transcription
      factors that is required for normal development of the pituitary gland. To date,
      only incompletely penetrant heterozygous mutations in LHX4 have been described in
      patients with variable combined pituitary hormone deficiencies.
      OBJECTIVE/HYPOTHESIS: To report a unique family with a novel recessive variant in
      LHX4 associated with a lethal form of congenital hypopituitarism that was
      identified through screening a total of 97 patients. METHOD: We screened 97
      unrelated patients with combined pituitary hormone deficiency, including 65% with
      an ectopic posterior pituitary, for variants in the LHX4 gene using Sanger
      sequencing. Control databases (1000 Genomes, dbSNP, Exome Variant Server, ExAC
      Browser) were consulted upon identification of variants. RESULTS: We identified
      the first novel homozygous missense variant (c.377C>T, p.T126M) in two deceased
      male patients of Pakistani origin with severe panhypopituitarism associated with
      anterior pituitary aplasia and posterior pituitary ectopia. Both were born small
      for gestational age with a small phallus, undescended testes, and mid-facial
      hypoplasia. The parents' first-born child was a female with mid-facial hypoplasia
      (DNA was unavailable). Despite rapid commencement of hydrocortisone and T4 in the
      brothers, all three children died within the first week of life. The
      LHX4(p.T126M) variant is located within the LIM2 domain, in a highly conserved
      location. The absence of homozygosity for the variant in over 65 000 controls
      suggests that it is likely to be responsible for the phenotype. CONCLUSION: We
      report, for the first time to our knowledge, a novel homozygous mutation in LHX4
      associated with a lethal phenotype, implying that recessive mutations in LHX4 may
      be incompatible with life.

PMID- 25871840
TI  - Gastric Emptying Is More Rapid in Adolescents With Type 1 Diabetes and Impacts on
      Postprandial Glycemia.
AB  - CONTEXT: Gastric emptying is a critical determinant of postprandial glycemic
      control in health and type 1 diabetes. There are few studies that assess the
      relationship between gastric emptying and postprandial glycaemia in adolescents
      with type 1 diabetes. OBJECTIVE: The objectives of the study were to quantify
      gastric emptying in adolescents with type 1 diabetes and examine its relationship
      to postprandial glycaemia and autonomic function. DESIGN: This was a case-control
      study. Gastric half-emptying time of a solid meal was measured by a (13)C
      octanoate breath test. Cardio-autonomic function was measured by heart rate
      variability. Chronic and postprandial gastrointestinal symptoms were evaluated by
      questionnaire and visual analog scales. Blood glucose concentrations were
      monitored frequently during the study. SETTING: The study was conducted at a
      tertiary pediatric hospital in South Australia. PARTICIPANTS: Thirty adolescents
      (aged 15 +/- 2.5 y) with type 1 diabetes and age- and sex-matched controls
      (gastric emptying, n = 20; heart rate variability, n = 135) participated in the
      study. MAIN OUTCOME: Gastric half-emptying time was the main outcome in the
      study. RESULTS: Gastric emptying was more rapid in subjects with type 1 diabetes
      than controls [median half emptying time 78 (interquartile range 61-99) vs 109
      (interquartile range 71-124) min, P = .02]. The postprandial rise in blood
      glucose at 60 minutes was strongly related to gastric half-emptying time (R = 
      0.65, P = .0001). Gastric emptying was slower in subjects with fasting
      hyperglycemia but was not related to heart rate variability. Nausea, bloating,
      and anxiety were related to fasting glycemia (P = .03). CONCLUSION: Rapid gastric
      emptying is a major determinant of postprandial glycemia in adolescents with type
      1 diabetes. This observation has significant implications for therapy.

PMID- 25871841
TI  - Template-directed assembly of metal-chalcogenide nanocrystals into ordered
      mesoporous networks.
AB  - Although great progress in the synthesis of porous networks of metal and metal
      oxide nanoparticles with highly accessible pore surface and ordered mesoscale
      pores has been achieved, synthesis of assembled 3D mesostructures of metal
      chalcogenide nanocrystals is still challenging. In this work we demonstrate that
      ordered mesoporous networks, which comprise well-defined interconnected metal
      sulfide nanocrystals, can be prepared through a polymer-templated oxidative
      polymerization process. The resulting self-assembled mesostructures that were
      obtained after solvent extraction of the polymer template impart the unique
      combination of light-emitting metal chalcogenide nanocrystals, three-dimensional
      open-pore structure, high surface area, and uniform pores. We show that the pore
      surface of these materials is active and accessible to incoming molecules,
      exhibiting high photocatalytic activity and stability, for instance, in oxidation
      of 1-phenylethanol into acetophenone. We demonstrate through appropriate
      selection of the synthetic components that this method is general to prepare
      ordered mesoporous materials from metal chalcogenide nanocrystals with various
      sizes and compositions. 

PMID- 25871842
TI  - Aberrant expression of miRNA and mRNAs in lesioned tissues of Graves' disease.
AB  - BACKGROUND AND AIMS: Abnormal microRNA (miRNA) expression is found in many
      diseases including autoimmune diseases. However, little is known about the role
      of miRNA regulation in Graves' disease (GD). Here, we simultaneously detected
      different expressions of miRNA and mRNAs in thyroid tissues via a high-throughput
      transcriptomics approach, known as microarray, in order to reveal the
      relationship between aberrant expression of miRNAs and mRNAs spectrum and GD.
      METHODS: Totally 7 specimens of thyroid tissue from 4 GD patients and 3 controls
      were obtained by surgery for microarray analysis. Then, 30 thyroid specimens (18
      GD and 12 controls) were also collected for further validation by quantitative
      real-time PCR ( qRT-PCR ). RESULTS: Statistical analysis showed that the
      expressions of 5 specific miRNA were increased significantly while those of other
      18 miRNA were decreased in thyroid tissue of GD patients (FC >= 1.3 or <= 0.77
      and p<0.05). In addition, the transcription of 1271 mRNAs was up-regulated, while
      the expression of 777 mRNAs transcripts was down-regulated (FC >= 2.0 or <= 0.5
      and p<0.05). Furthermore, integrated analysis of differentially expressed miRNA
      and their target mRNAs demonstrated that 2 miRNA (miR-22 and miR-183) were
      increased while their potential target mRNAs were decreased. 3 miRNA (miR-101,
      miR-197 and miR-660) were decreased while their potential target mRNAs were
      increased. The above findings from microarray screening were confirmed by qRT-PCR
      in more samples. The results were consistent with those observed in the
      microarray assays. CONCLUSION: Our study highlights the possibility that miRNA
      target gene network may be involved in the pathogenesis of GD and could provide
      new insights into understanding the pathophysiological mechanisms of GD.

PMID- 25871843
TI  - Nephrosclerosis: a term in quest of a disease.
AB  - For a century, nephrosclerosis was ascribed to nonmalignant hypertension and
      aging. However, it was intuitively perceived that hypertension may follow rather
      than explain this nephrovasculopathy. Hypertensive nephrosclerosis was long
      considered a major cause of end-stage renal failure (ESRD). This is especially
      true in blacks of African descent but not in other ethnic populations. The term
      'nephrosclerosis' is still an easy way out to classify a patient with renal
      insufficiency. This leads to neglect the possibility of an overlooked nephropathy
      complicated by hypertension and to believe that drastic blood pressure control
      may retard the progression to ESRD. Several clinical and experimental lines of
      evidence lead to the understanding that nephrosclerosis, especially in blacks, is
      a genetic renovasculopathy that precedes the rise in blood pressure. The
      identification of coding region variants in APOL1 encoding apolipoprotein L-1 in
      black but also white and Asians opens new lines of research on the genetics of
      nephroangiosclerosis and of FSGS. Metabolic derangements, such as obesity,
      oxidative stress, dyslipidemia and atherosclerosis may be considered confounding
      factors with regard to nephrosclerosis. Histomorphometric studies led to sorting
      out the lesions due to aging from those stemming from hypertension. They shed new
      light not only on glomerular lesions that comprise ischemic obsolescence but also
      on glomerulomegaly and focal-segmental sclerosis, the latter due to a loss of
      renal autoregulation. It appears that the control of hypertension is not credited
      with the expected benefit for slowing the decline of renal function.
      'Nephrosclerosis' can be considered an umbrella term of poor significance that
      should be replaced by its pathologic description, that is, arterionephrosclerosis
      and incite to elucidate the various genetic and metabolic factors that lead to a
      lesion in quest of a specific disease.

PMID- 25871844
TI  - Abortion law across Australia--A review of nine jurisdictions.
AB  - This article reviews the current legal status of abortion in Australia and its
      implications. Australian abortion law has been a matter for the states since
      before Federation. In the years since Federation there have been significant
      reforms and changes in the abortion laws of some jurisdictions, although not all.
      Across Australia there are now nine sets of laws, state and Commonwealth,
      concerned with abortion. The test of a lawful abortion varies greatly across
      jurisdictions. In a number of states and territories, it is necessary to
      establish a serious risk to the physical or mental health of the woman if the
      pregnancy was to continue. In some cases, the certification of two doctors is
      required, particularly for abortions at later gestations. There are also physical
      restrictions on access, such as in South Australia and the Northern Territory
      where abortion must take place in a hospital. Only in the ACT has abortion been
      removed from the criminal law altogether. Variations in the law and restrictions
      arising from these are not consistent with the aims and provision of the
      universal, accessible health care system aspired to in Australia. There is an
      urgent need for overall reform and the introduction of uniformity to Australia's
      abortion laws, including removal of abortion from the criminal law. 

PMID- 25871845
TI  - Adsorption on ordered and disordered duplex layers of porous anodic alumina.
AB  - We have carried out systematic experiments and numerical simulations of the
      adsorption on porous anodic aluminum oxide (AAO) duplex layers presenting either
      an ordered or a disordered interconnecting interface between the large (cavity)
      and small (constriction) sections of the structured pores. Selective blocking of
      the pore openings resulted in three different pore topologies: open structured
      pores, funnel pores, and ink-bottle pores. In the case of the structured pores
      having an ordered interface, the adsorption isotherms present a rich
      phenomenology characterized by the presence of two steps in the condensation
      branch and the opening of one (two) hysteresis loops during evaporation for the
      ink-bottle (open and funnel) pores. The isotherms can be obtained by summing the
      isotherms measured on uniform pores having the dimensions of the constrictions or
      of the cavities. The numerical analysis of the three different pore topologies
      indicates that the shape of the junction between the two pore sections is only
      important for the adsorption branch. In particular, a conic junction which
      resembles that of the AAO pores represents the experimental isotherms for the
      open and funnel pores better, but the shape of the junction in the ink bottle
      pores does not matter. The isotherms for the duplex layers with a disordered
      interface display the same general features found for the ordered duplex layers.
      In both cases, the adsorption branches coincide and have two steps which are
      shifted to lower relative pressures compared to those for the ordered duplex.
      Furthermore, the desorption branches comprise hysteresis loops much wider than
      those of the ordered duplex layers. Overall, this study highlights the important
      role played by morphologies where there are interconnections between large and
      small pores. 

PMID- 25871846
TI  - Additive effects on the energy barrier for synaptic vesicle fusion cause
      supralinear effects on the vesicle fusion rate.
AB  - The energy required to fuse synaptic vesicles with the plasma membrane
      ('activation energy') is considered a major determinant in synaptic efficacy.
      From reaction rate theory, we predict that a class of modulations exists, which
      utilize linear modulation of the energy barrier for fusion to achieve supralinear
      effects on the fusion rate. To test this prediction experimentally, we developed
      a method to assess the number of releasable vesicles, rate constants for vesicle
      priming, unpriming, and fusion, and the activation energy for fusion by fitting a
      vesicle state model to synaptic responses induced by hypertonic solutions. We
      show that complexinI/II deficiency or phorbol ester stimulation indeed affects
      responses to hypertonic solution in a supralinear manner. An additive vs
      multiplicative relationship between activation energy and fusion rate provides a
      novel explanation for previously observed non-linear effects of
      genetic/pharmacological perturbations on synaptic transmission and a novel
      interpretation of the cooperative nature of Ca(2+)-dependent release. 

PMID- 25871849
TI  - Asymmetric Synthesis of Dihydronaphthoquinones Containing Adjacent Stereocenters
      via a Sulfa-Michael Addition Triggered Ring-Expansion Approach.
AB  - A novel asymmetric synthetic approach for the construction of enantioenriched
      functionalized dihydroquinones incorporating adjacent quaternary and tertiary
      stereocenters has been reported, in which enantioenriched 3-allylic phthalides
      engaged in an unprecedented sulfa-Michael addition-triggered stereoselective ring
      expansion reaction, and furnished the desired sulfur-incoporated
      dihydronaphthoquinones with high stereoselectivity. 

PMID- 25871847
TI  - Reconstitution of a eukaryotic replisome reveals suppression mechanisms that
      define leading/lagging strand operation.
AB  - We have reconstituted a eukaryotic leading/lagging strand replisome comprising 31
      distinct polypeptides. This study identifies a process unprecedented in bacterial
      replisomes. While bacteria and phage simply recruit polymerases to the fork, we
      find that suppression mechanisms are used to position the distinct eukaryotic
      polymerases on their respective strands. Hence, Pol epsilon is active with CMG on
      the leading strand, but it is unable to function on the lagging strand, even when
      Pol delta is not present. Conversely, Pol delta-PCNA is the only enzyme capable
      of extending Okazaki fragments in the presence of Pols epsilon and alpha. We have
      shown earlier that Pol delta-PCNA is suppressed on the leading strand with CMG
      (Georgescu et al., 2014). We propose that CMG, the 11-subunit helicase, is
      responsible for one or both of these suppression mechanisms that spatially
      control polymerase occupancy at the fork. 

PMID- 25871848
TI  - Constraint and divergence of global gene expression in the mammalian embryo.
AB  - The effects of genetic variation on gene regulation in the developing mammalian
      embryo remain largely unexplored. To globally quantify these effects, we crossed
      two divergent mouse strains and asked how genotype of the mother or of the embryo
      drives gene expression phenotype genomewide. Embryonic expression of 331 genes
      depends on the genotype of the mother. Embryonic genotype controls allele
      specific expression of 1594 genes and a highly overlapping set of cis-expression
      quantitative trait loci (eQTL). A marked paucity of trans-eQTL suggests that the
      widespread expression differences do not propagate through the embryonic gene
      regulatory network. The cis-eQTL genes exhibit lower-than-average evolutionary
      conservation and are depleted for developmental regulators, consistent with
      purifying selection acting on expression phenotype of pattern formation genes.
      The widespread effect of maternal and embryonic genotype in conjunction with the
      purifying selection we uncovered suggests that embryogenesis is an important and
      understudied reservoir of phenotypic variation. 

PMID- 25871851
TI  - Magnetoelectric CoFe2O4/polyvinylidene fluoride electrospun nanofibres.
AB  - Magnetoelectric 0-1 composites comprising CoFe2O4 (CFO) nanoparticles in a
      polyvinylidene fluoride (PVDF) polymer-fibre matrix have been prepared by
      electrospinning. The average diameter of the electrospun composite fibres is ~325
      nm, independent of the nanoparticle content, and the amount of the crystalline
      polar beta phase is strongly enhanced when compared to pure PVDF polymer fibres.
      The piezoelectric response of these electroactive nanofibres is modified by an
      applied magnetic field, thus evidencing the magnetoelectric character of the
      CFO/PVDF 0-1 composites. 

PMID- 25871850
TI  - Inhibition of Sphingosine Kinase 1 Ameliorates Angiotensin II-Induced
      Hypertension and Inhibits Transmembrane Calcium Entry via Store-Operated Calcium
      Channel.
AB  - Angiotensin II (AngII) plays a critical role in the regulation of vascular tone
      and blood pressure mainly via regulation of Ca(2+) mobilization. Several reports
      have implicated sphingosine kinase 1 (SK1)/sphingosine 1-phosphate (S1P) in the
      mobilization of intracellular Ca(2+) through a yet-undefined mechanism. Here we
      demonstrate that AngII-induces biphasic calcium entry in vascular smooth muscle
      cells, consisting of an immediate peak due to inositol tris-phosphate-dependent
      release of intracellular calcium, followed by a sustained transmembrane Ca(2+)
      influx through store-operated calcium channels (SOCs). Inhibition of SK1
      attenuates the second phase of transmembrane Ca(2+) influx, suggesting a role for
      SK1 in AngII-dependent activation of SOC. Intracellular S1P triggers SOC
      dependent Ca(2+) influx independent of S1P receptors, whereas external
      application of S1P stimulated S1P receptor-dependent Ca(2+) influx that is
      insensitive to inhibitors of SOCs, suggesting that the SK1/S1P axis regulates
      store-operated calcium entry via intracellular rather than extracellular actions.
      Genetic deletion of SK1 significantly inhibits both the acute hypertensive
      response to AngII in anaesthetized SK1 knockout mice and the sustained
      hypertensive response to continuous infusion of AngII in conscious animals.
      Collectively these data implicate SK1 as the missing link that connects the
      angiotensin AT1A receptor to transmembrane Ca(2+) influx and identify SOCs as a
      potential intracellular target for SK1. 

PMID- 25871852
TI  - Remote chemotherapy supervision model for rural cancer care: perspectives of
      health professionals.
AB  - Townsville Cancer Centre (TCC), a tertiary cancer centre in North Queensland,
      Australia, provides chemotherapy services to surrounding small rural towns using
      the Queensland Remote Chemotherapy Supervision model (QReCS). Under this model,
      selected chemotherapy regimens are administered in rural hospitals by rural based
      generalist doctors and nurses, under the supervision of TCC-based medical
      oncologists and chemotherapy competent nurses through videoconferencing. We
      sought to explore the perspectives of health professionals participating in
      QReCS. This qualitative study used semi-structured interviews with 19
      participants, including nine nurses, eight doctors, one rural pharmacist and one
      administration officer. The interviews were recorded and transcribed. Transcripts
      were examined using iterative thematic analysis. Four major themes were
      identified from the data: (1) benefits of the model, (2) enablers of
      implementation, (3) operational requirements for optimal functioning and (4)
      disadvantages of the model. The reported benefits of the model were patient
      convenience, inter-professional communication across health district borders,
      expanded scope of practice, continuity of care and maintenance of patient safety
      and compliance with guidelines while delivering chemotherapy. Further
      improvements in the quality of training for rural nurses, coordination between
      urban and rural sites and between health professionals and documentation of
      clinical encounters would optimise the operation of the model. QReCS appears to
      provide many benefits to patients and health professionals and a framework for
      safe administration of chemotherapy in rural areas. Coordination of care, the
      quality of training for rural nurses as well as clinical documentation needs to
      improve to optimise the operation of the model. 

PMID- 25871853
TI  - Graphdiyne oxides as excellent substrate for electroless deposition of Pd
      clusters with high catalytic activity.
AB  - Graphdiyne (GDY), a novel kind of two-dimensional carbon allotrope consisting of
      sp- and sp(2)-hybridized carbon atoms, is found to be able to serve as the
      reducing agent and stabilizer for electroless deposition of highly dispersed Pd
      nanoparticles owing to its low reduction potential and highly conjugated
      electronic structure. Furthermore, we observe that graphdiyne oxide (GDYO), the
      oxidation form of GDY, can be used as an even excellent substrate for electroless
      deposition of ultrafine Pd clusters to form Pd/GDYO nanocomposite that exhibits a
      high catalytic performance toward the reduction of 4-nitrophenol. The high
      catalytic performance is considered to benefit from the rational design and
      electroless deposition of active metal catalysts with GDYO as the support. 

PMID- 25871854
TI  - To Pretreat or Not to Pretreat: Prophylactic Anticholinergic Administration
      Before Dexmedetomidine in Pediatric Imaging.
AB  - BACKGROUND: Dexmedetomidine (Dex) appears to be very effective as a sole sedative
      for pediatric imaging when used at high doses, but at an increased risk of
      transient hypertension, hypotension, and bradycardia. There are no clinical
      evidence/guidelines to guide anesthesia providers as to whether patients should
      be pretreated with an anticholinergic. The aim of this study was to demonstrate
      the changes in hemodynamic parameters after Dex sedation attributed to receiving
      or not receiving an anticholinergic pretreatment and compare for any differences
      or similarities. A subgroups analysis was performed in children with Down
      syndrome (DS). METHODS: In this retrospective descriptive study, we reviewed the
      records of 163 children receiving Dex anesthesia during MRI studies. Data
      analyzed included demographics, history of DS, and hemodynamics (heart rate [HR],
      systolic blood pressure [SBP], and diastolic blood pressure [DBP]) following Dex
      loading and infusion and the administration of an anticholinergic (atropine or
      glycopyrrolate). RESULTS: The mean age was 94.5 months, and 52 (32%) patients had
      DS. The generalized linear mixed-effects regression model showed a significant
      reduction in HR and SBP in all patients when no anticholinergic was administered
      compared with when it was administered. There was no significant change with DBP.
      During the scan period, the HR of the no-anticholinergic group decreased 26.6%,
      whereas that of the anticholinergic group decreased by only 16.7% from baseline
      (P < 0.01). The maximal SBP increased by a significantly greater percentage,
      compared with baseline, in the anticholinergic group in comparison with the no
      anticholinergic group (20.2% vs 10.4%, respectively; P = 0.02). In the DS group,
      the difference in the maximal SBP change during the scan period was exaggerated,
      with a percentage increase that was 36 times larger in the anticholinergic group
      compared with the no-anticholinergic group (22% vs 0.6%, respectively; P< 0.01).
      CONCLUSIONS: Administration of a prophylactic anticholinergic with Dex shows no
      advantage other than a transient clinically insignificant increase in HR and SBP,
      and it may precipitate transient exaggerated SBP in more patients compared with
      not using a prophylactic anticholinergic.

PMID- 25871855
TI  - Temporal Epidemiology of Sudden Oak Death in Oregon.
AB  - An effort to eradicate Phytophthora ramorum, causal agent of sudden oak death,
      has been underway since its discovery in Oregon forests. Using an information
      theoretical approach, we sought to model yearly variation in the size of newly
      infested areas and dispersal distance. Maximum dispersal distances were best
      modeled by spring and winter precipitation 2 years before detection, and
      infestation size the year prior. Infestation size was best modeled by infestation
      size and spring precipitation the year prior. In our interpretation, there is a 2
      year delay between the introduction of inoculum and onset of mortality for a
      majority of sites. The year-long gap in between allows ample time for the
      production of inoculum contributing to the spread of P. ramorum. This is
      supported by epidemic development following changes in eradication protocols
      precipitated by an outbreak in 2011, attributable to a 2009 treatment delay and
      an uncharacteristically wet spring in 2010. Posteradication, we have observed an
      increase in the total area of new outbreaks and increased frequency in dispersal
      distances greater than 4 km. Although the eradication program has not eliminated
      P. ramorum from Oregon forests, it has likely moderated this epidemic,
      emphasizing the need for prompt treatment of future invasive forest pathogens. 

PMID- 25871856
TI  - Inhibition of Phytophthora parasitica and P. capsici by Silver Nanoparticles
      Synthesized Using Aqueous Extract of Artemisia absinthium.
AB  - Application of nanoparticles for controlling plant pathogens is a rapidly
      emerging area in plant disease management, and nanoparticles synthesis methods
      that are economical and ecofriendly are extensively investigated. In this
      project, we investigated the potential of silver nanoparticles (AgNPs)
      synthesized with aqueous extract of Artemisia absinthium against several
      Phytophthora spp., which cause many economically important crop diseases. In in
      vitro dose-response tests conducted in microtiter plates, 10 ug ml-1 of AgNPs
      inhibited mycelial growth of P. parasitica, P. infestans, P. palmivora, P.
      cinnamomi, P. tropicalis, P. capsici, and P. katsurae. Detailed in vitro dose
      response analyses conducted with P. parasitica and P. capsici revealed that AgNPs
      synthesized with A. absinthium extract were highly potent (IC50: 2.1 to 8.3 ug ml
      1) and efficacious (100%) in inhibiting mycelial growth, zoospore germination,
      germ tube elongation, and zoospore production. Interestingly, AgNP treatment
      accelerated encystment of zoospores. Consistent with in vitro results, in planta
      experiments conducted in a greenhouse revealed that AgNP treatments prevented
      Phytophthora infection and improved plant survival. Moreover, AgNP in in planta
      experiments did not produce any adverse effects on plant growth. These
      investigations provide a simple and economical method for controlling
      Phytophthora with AgNP without affecting normal plant physiology.

PMID- 25871859
TI  - MILDEW LOCUS O Mutation Does Not Affect Resistance to Grain Infections with
      Fusarium spp. and Ramularia collo-cygni.
AB  - MILDEW LOCUS O defines a major susceptibility gene for powdery mildew, and
      recessive mlo resistance alleles are widely used in breeding for powdery mildew
      resistance in spring barley. Barley powdery mildew resistance, which is conferred
      by mlo genes, is considered to be costly in terms of spontaneous defense
      reactions and enhanced susceptibility to cell-death-inducing pathogens. We
      assessed fungal infestation of barley (Hordeum vulgare) grain by measuring fungal
      DNA after natural infection with Fusarium spp. and Ramularia collo-cygni or after
      inoculation with Fusarium spp. in the field. Powdery-mildew-resistant mlo5
      genotypes did not show enhanced Fusarium spp. or R. collo-cygni DNA content of
      grain over four consecutive years. Data add to our understanding of pleiotropic
      effects of mlo-mediated powdery mildew resistance and contributes to the
      discussion of whether or not application of barley mlo mutations may support
      pathogenesis of cell-death-inducing fungal pathogens under field conditions. 

PMID- 25871862
TI  - Local allergic nasal reactions convert to classic systemic allergic reactions: a
      long-term follow-up.
AB  - BACKGROUND: There is poor knowledge about the evolution of the negative skin test
      in local allergy over time. Does the negative skin test of patients with local
      allergies remain negative permanently or does it become positive? METHODS: We
      describe our long-term observation concerning the evolution of the negative skin
      test over time. This is a retrospective, follow-up study using data from the
      medical records of a group of patients with local allergy. A total of 42 patients
      aged between 3 and 70 years (median age: 31.5 years) were studied. The duration
      of follow-up varied from 1 to 27 years. Skin tests were performed using the skin
      prick test and intracutaneous techniques for pollen, molds, mites, feathers
      (goose and duck) and animal danders. Nasal provocation tests were conducted with
      the same allergens. Additionally, specific IgE in 17 patients was measured by
      enzyme allergosorbent test. RESULTS: During the period of observation, the
      negative skin test reactions converted into positive reactions in 17 patients
      (40%). In addition to the negative skin reactions, 55% of the patients also
      presented positive skin reactions. The conversion rate was higher in children and
      adolescents than in adults. In 4 patients, conversions occurred >7 years after
      the initial examination. Specific IgE was negative in all but 2 patients, in whom
      the conversion in the skin test was accompanied by a switch from negative to
      positive specific IgE. CONCLUSION: Conversions from local to classic systemic
      respiratory allergic reactions appear to be a common phenomenon.

PMID- 25871863
TI  - Predictors of Suicidality Among Patients with Psychotic Disorders in a Partial
      Hospital Treatment Program.
AB  - Individuals with psychotic disorders are at increased risk for suicidality.
      Demographic and clinical characteristics were compared in individuals with
      psychotic disorders reporting either high or low suicidality. Among this sample
      of 259 partial hospital patients, 116 (44.8%) were classified as high risk on the
      suicidality section of the Mini Neuropsychiatric Interview, and 143 (55.2%) were
      considered low risk. Bivariate analyses revealed that patients classified as high
      risk demonstrated greater depression severity, more relationship difficulties,
      greater emotional lability, and more substance use problems. A logistic
      regression model indicated that substance use was the most powerful predictor of
      higher levels of suicidality. Monitoring and intervention for substance use
      should be targeted as a particularly important aspect of treatment for acutely
      ill patients diagnosed with psychotic disorders. 

PMID- 25871860
TI  - Testing Taxonomic Predictivity of Foliar and Tuber Resistance to Phytophthora
      infestans in Wild Relatives of Potato.
AB  - Potato late blight, caused by the oomycete phytopathogen Phytophthora infestans,
      is a devastating disease found in potato-growing regions worldwide. Long-term
      management strategies to control late blight include the incorporation of host
      resistance to predominant strains. However, due to rapid genetic changes within
      pathogen populations, rapid and recurring identification and integration of novel
      host resistance traits is necessary. Wild relatives of potato offer a rich source
      of desirable traits, including late blight resistance, but screening methods can
      be time intensive. We tested the ability of taxonomy, ploidy, crossing group,
      breeding system, and geography to predict the presence of foliar and tuber late
      blight resistance in wild Solanum spp. Significant variation for resistance to
      both tuber and foliar late blight was found within and among species but there
      was no discernable predictive power based on taxonomic series, clade, ploidy,
      breeding system, elevation, or geographic location. We observed a moderate but
      significant correlation between tuber and foliar resistance within species.
      Although previously uncharacterized sources of both foliar and tuber resistance
      were identified, our study does not support an assumption that taxonomic or
      geographic data can be used to predict sources of late blight resistance in wild
      Solanum spp. 

PMID- 25871861
TI  - Effect of mirtazapine on rat bone tissue after orchidectomy.
AB  - OBJECTIVE: Our study aimed to investigate the effect of mirtazapine on bone
      metabolism in the orchidectomized rat model. METHODS: Rats were divided into
      three groups. A sham-operated control group (SHAM group) and a control group
      after orchidectomy (ORX group) received the standard laboratory diet (SLD). An
      experimental group after orchidectomy (ORX MIRTA group) received SLD enriched
      with mirtazapine for 12 weeks. Bone mineral density (BMD) was measured by dual
      energy X-ray absorptiometry. Bone marker concentrations of osteoprotegerin (OPG),
      amino-terminal propeptide of procollagen type I, bone alkaline phosphatase
      (BALP), sclerostin and bone morphogenetic protein 2 were examined in bone
      homogenate. The femurs were used for biomechanical testing. RESULTS: Compared
      with the control ORX group, we found a lower BMD in the ORX MIRTA group. The
      differences were statistically significant, although not in the lumbar vertebrae.
      BMD was lower in the MIRTA group, suggesting a preferential effect on cortical
      bone. However, although the thickness of the diaphyseal cortical bone was not
      different, the fragility in the femoral neck area was statistically significantly
      different between the groups in biomechanical testing. Regarding the bone
      metabolism markers, there was a significant decrease in OPG and BALP levels,
      suggesting a reduction in osteoid synthesis. CONCLUSIONS: The results suggest
      that prolonged use of mirtazapine may have a negative effect on the synthesis of
      bone and on its mechanical strength, especially in the femoral neck. Further
      studies are warranted to establish whether mirtazapine may have a clinically
      significant adverse effect on bone exclusively in the model of gonadectomized
      rats, or whether the effect occurs also in the model of gonadally intact animals
      and in respective human models.

PMID- 25871858
TI  - Molecular Mapping of YrSP and Its Relationship with Other Genes for Stripe Rust
      Resistance in Wheat Chromosome 2BL.
AB  - Stripe rust, caused by Puccinia striiformis f. sp. tritici, is an important
      disease of wheat worldwide. Resistance is the best way to control the disease.
      YrSP, a gene originally from 'Spaldings Prolific' wheat and providing resistance
      to a broad spectrum of races, is used for differentiating P. striiformis f. sp.
      tritici races but its chromosomal location is not clear. To map YrSP, a near
      isogenic line (AvSYrSPNIL) was backcrossed to the recurrent parent, Avocet S.
      Genetic analysis of the BC7F1, BC8, BC7F2, and BC7F3 progenies confirmed a single
      dominant gene for resistance. In total, 182 BC7F2 plants and their derived BC7F3
      lines were phenotyped with an avirulent P. striiformis f. sp. tritici race and
      genotyped with simple-sequence repeat (SSR), single-nucleotide polymorphism
      (SNP), and sequence-tagged site (STS) markers. A linkage map was constructed with
      3 SSR, 17 SNP, and 3 STS markers covering 23.3 centimorgans (cM). Markers IWA638
      and dp269 were 0.6 cM proximal and 1.5 cM distal, respectively, to YrSP. The gene
      was mapped in chromosome bin 2BL-C-0.5, physically within the proximal 50% of the
      chromosome 2BL arm. Allelism tests based on F2 phenotypes indicated that YrSP is
      closely linked to but not allelic with genes Yr5, Yr7, Yr43, Yr44, and Yr53.
      Infection type data from tests with 10 historical and currently predominant P.
      striiformis f. sp. tritici races in the United States also demonstrated
      differences in specificity between YrSP and the other genes. The specificity of
      YrSP is useful in differentiating P. striiformis f. sp. tritici races and
      studying the plant-pathogen interactions, and the information of chromosomal
      location of the gene and its tightly linked markers should be useful in
      developing resistant cultivars when combined with other genes for resistance to
      stripe rust. 

PMID- 25871864
TI  - Nursing ethics: what would you do?

PMID- 25871865
TI  - Innovations in subcutaneous infusions.
AB  - Parenteral drug delivery is an essential part of patient care. The subcutaneous
      (SC) route is easily accessed, is more cost-effective, and provides increased
      convenience for the patient than the other parenteral methods. The
      pharmacokinetic profile of medications delivered SC reflect bioavailabilities
      similar to intravenous (IV) delivery. The coadministration of human recombinant
      hyaluronidase with SC medications enhances the maximum concentration and time to
      maximum concentration to more closely mimic drugs delivered by the IV route.
      Pharmaceutical companies are studying and successfully developing new
      formulations of current medications for delivery via the SC route. 

PMID- 25871866
TI  - Accepted but unacceptable: peripheral IV catheter failure.
AB  - Peripheral intravenous (IV) catheter insertion, the most common invasive hospital
      procedure performed worldwide, is associated with a variety of complications and
      an unacceptably high overall failure rate of 35% to 50% in even the best of
      hands. Catheter failure is costly to patients, caregivers, and the health care
      system. Although advances have been made, analysis of the mechanisms underlying
      the persistent high rate of peripheral IV failure reveals opportunities for
      improvement. 

PMID- 25871867
TI  - Drug shortages and patient safety: an overview of essential information for the
      infusion nurse.
AB  - Drug shortages present a growing problem in the United States, with the majority
      of shortages occurring among sterile injectable medications. Although the impact
      of shortages has been shown to adversely affect patient care in a variety of
      settings, those who are dependent on outpatient or home infusion therapy are
      especially vulnerable. Legislative action and the efforts of the U.S. Food and
      Drug Administration have helped reduce the occurrence of new shortages; however,
      the problem is not likely to be eliminated in the short term and requires
      effective management strategies. 

PMID- 25871868
TI  - Renal dosing in high-risk populations.
AB  - In patients with diminished kidney function, the pharmacokinetics of many
      medications are altered. Alterations in absorption, distribution, and metabolism
      are observed in addition to altered elimination through the kidney. Classes of
      intravenous medications in which dose modifications are frequently required for
      patients with diminished kidney function include antibiotics, some
      anticoagulants, and chemotherapy agents. Failure to follow renal dose adjustment
      recommendations can lead to an increased risk of toxicity. Equations frequently
      used to estimate kidney function for the purpose of making renal dose adjustments
      include the Cockcroft-Gault, Modification of Diet in Renal Disease (MDRD), and
      Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. 

PMID- 25871870
TI  - Root cause analysis in infusion nursing: applying quality improvement tools for
      adverse events.
AB  - The application of root cause analysis (RCA) to health care began in the
      Veteran's Administration system and spread to Joint Commission-accredited
      organizations when it became a requirement for accreditation. The success of this
      valuable quality improvement tool relies on understanding the principles of
      patient safety, assembling a team, and producing and completing action items
      aimed at correcting root causes of adverse events. This article describes optimal
      RCA techniques based on published literature and expert opinion and then provides
      a sample RCA for a fictitious but common adverse event: catheter-associated
      bloodstream infection. 

PMID- 25871869
TI  - Supra-plasma expanders: the future of treating blood loss and anemia without red
      cell transfusions?
AB  - Oxygen delivery capacity during profoundly anemic conditions depends on blood's
      oxygen-carrying capacity and cardiac output. Oxygen-carrying blood substitutes
      and blood transfusion augment oxygen-carrying capacity, but both have given rise
      to safety concerns, and their efficacy remains unresolved. Anemia decreases
      oxygen-carrying capacity and blood viscosity. Present studies show that
      correcting the decrease of blood viscosity by increasing plasma viscosity with
      newly developed plasma expanders significantly improves tissue perfusion. These
      new plasma expanders promote tissue perfusion, increasing oxygen delivery
      capacity without increasing blood oxygen-carrying capacity, thus treating the
      effects of anemia while avoiding the transfusion of blood. 

PMID- 25871871
TI  - Corvis ST Tonometer for Measuring Postoperative IOP in LASIK Patients.
AB  - PURPOSE: To compare the postoperative measurements of intraocular pressure (IOP)
      using the Corvis ST Tonometer (CST), ocular response analyzer (ORA), and Goldmann
      applanation tonometry (GAT) in eyes undergoing laser in situ keratomileusis
      (LASIK), as well as to analyze the relationship between the corneal biomechanical
      parameters of the CST and the ORA. METHODS: Fifty participants who had undergone
      LASIK to treat myopia in the previous 3 months were enrolled. Postoperative IOP
      measurements of these participants were obtained using the CST, ORA (corneal
      compensated IOP [IOPcc], Goldmann-correlated IOP [IOPg]), and GAT. Device
      agreement was calculated by Bland-Altman analysis. The metrics of corneal
      biomechanical properties were recorded using the ORA and the CST. Corneal
      biomechanical parameters were compared. RESULTS: The Bland-Altman analysis
      revealed a significant bias between CST and GAT, between CST and IOPcc, and
      between CST and IOPg of 3.4, 1.0, and 3.8, mm Hg, respectively, with 95% limits
      of agreement of -0.7 to 7.5 mm Hg, -2.1 to 4.2 mm Hg, and -0.4 to 8.0 mm Hg. The
      ORA-derived IOP measurements, CST-derived IOP, and GAT IOP values showed good
      correlation with each other. The CST IOP and IOPcc were higher than the GAT IOP
      (all p < 0.05), whereas IOPg did not differ from the GAT IOP readings. Ocular
      response analyzer-derived corneal biomechanical parameters (corneal hysteresis
      and the corneal resistance factor) showed significant correlations with CST
      derived parameters, including the maximum deformation amplitude at the corneal
      apex and the time from start until the first applanation. CONCLUSIONS: The CST
      offers an alternative method for measuring postoperative IOP in LASIK patients,
      and it appears to obtain higher IOP values than other tonometry techniques. The
      technique may facilitate the investigation of corneal biomechanical property
      changes in LASIK-treated eyes.

PMID- 25871872
TI  - Characteristic OCT Pattern in Waldenstrom Macroglobulinemia.
AB  - PURPOSE: To report characteristic optical coherence tomography (OCT) patterns as
      a guide in diagnosis of Waldenstrom macroglobulinemia in a patient presenting
      with bilateral vision loss. CASE REPORT: A 60-year-old male patient presented
      with bilateral sudden-onset vision loss and low-grade fever. The patient had
      bilateral exudative retinal detachment involving the macula. Spectral domain OCT
      revealed neurosensory detachment along with a very regular and harmonious cystoid
      change in the outer retina as well as deposits around photoreceptors. The patient
      had lymphadenopathy and hepatosplenomegaly. Serum protein electrophoresis showed
      the presence of M band in the gamma globulin region, which, on immune fixation,
      showed a monoclonal band at the "IgM and K" region. Infiltration by
      lymphoplasmacytic proliferative cells with secondary myelofibrosis was seen in
      the bone marrow biopsy specimen. The immunophenotype scattergram of
      lymphoplasmacytic proliferative cells of bone marrow showed no light-chain
      expression, and the cells were brightly positive for CD19, CD5, and CD20.
      Quantitative assay of immunoglobulin M was 10,057 mg/dL. CONCLUSIONS: Spectral
      domain OCT showing a harmonious and regular cystoid pattern and deposits around
      photoreceptors was a guide in our diagnosis of this case of Waldenstrom
      macroglobulinemia presenting with retinal detachment and retinal deposits.

PMID- 25871873
TI  - Intravitreal aflibercept after bilateral bevacizumab-induced iritis.
AB  - PURPOSE: To present a case of neovascular age-related macular degeneration
      treated with aflibercept intravitreal injections after bilateral bevacizumab
      injections, administered on separate dates, resulted in bilateral iritis. CASE
      REPORT: A 73-year-old woman with a previous history of two episodes of
      nongranulomatous iritis in her right eye that was believed to be associated with
      her systemic diagnosis of rheumatoid arthritis was treated with intravitreal
      bevacizumab injections for bilaterally occurring neovascular age-related macular
      degeneration. Initial bevacizumab injections in each eye administered
      sequentially over a week's time resulted in immediate-onset nongranulomatous
      iritis in each eye. Subsequent intravitreal injections of aflibercept were
      administered, and therapeutic benefit was achieved without occurrence of iritis.
      CONCLUSIONS: In cases where intravitreal bevacizumab results in anterior uveitis,
      aflibercept may be a safe alternative therapeutic choice for the treatment of
      neovascular age-related macular degeneration.

PMID- 25871874
TI  - The readmissions obsession and magical numbers.

PMID- 25871875
TI  - Sonic hedgehog signaling mediates resveratrol to increase proliferation of neural
      stem cells after oxygen-glucose deprivation/reoxygenation injury in vitro.
AB  - BACKGROUND/AIMS: There is interest in drugs and rehabilitation methods to enhance
      neurogenesis and improve neurological function after brain injury or
      degeneration. Resveratrol may enhance hippocampal neurogenesis and improve
      hippocampal atrophy in chronic fatigue mice and prenatally stressed rats.
      However, its effect and mechanism of neurogenesis after stroke is less well
      understood. Sonic hedgehog (Shh) signaling is crucial for neurogenesis in the
      embryonic and adult brain, but relatively little is known about the role of Shh
      signaling in resveratrol-enhanced neurogenesis after stroke. METHODS: Neural stem
      cells (NSCs) before oxygen-glucose deprivation/reoxygenation (OGD/R) in vitro
      were pretreated with resveratrol with or without cyclopamine. Survival and
      proliferation of NSCs was assessed by the CCK8 assay and BrdU immunocytochemical
      staining. The expressions and activity of signaling proteins and mRNAs were
      detected by immunocytochemistry, Western blotting, and RT-PCR analysis. RESULTS:
      Resveratrol significantly increased NSCs survival and proliferation in a
      concentration-dependent manner after OGD/R injury in vitro. At the same time, the
      expression of Patched-1, Smoothened (Smo), and Gli-1 proteins and mRNAs was
      upregulated, and Gli-1 entered the nucleus, which was inhibited by cyclopamine, a
      Smo inhibitor. CONCLUSION: Shh signaling mediates resveratrol to increase NSCs
      proliferation after OGD/R injury in vitro.

PMID- 25871876
TI  - Response to Comment on "Enhanced Elimination of Perfluorooctane Sulfonic Acid by
      Menstruating Women: Evidence from Population-based Pharmacokinetic Modeling".

PMID- 25871878
TI  - Dynamic control of Th2 cell responses by STAT3 during allergic lung inflammation
      in mice.
AB  - Signal transducer and activator of transcription (STAT) family molecules play
      essential roles during the differentiation of helper T cells from naive
      precursors. Although the role of STAT3 in driving Th17 cell polarization has been
      well established, its role on Th2 responses to allergens remains incompletely
      understood. By employing T cell-specific STAT3 deficient mice, we demonstrate
      that STAT3 in T cells plays diverse role on Th2 cells depending on their
      locations in an animal model of allergic asthma. In the bronchial lymph nodes,
      STAT3-deficient T cells produced significantly reduced levels of Th2 cytokines.
      The frequencies of Th2 cells among CD4(+) T cells in the lung were comparable
      between STAT3-sufficient and STAT3-deficient T cells. By contrast, STAT3
      deficient T cells in the airway exhibited significantly enhanced production of
      Th2 cell cytokines compared to STAT3-sufficient T cells. Interestingly, a major
      population of IL-4/5 producers among STAT3-deficient T cells in the airway co
      produced IFNgamma. The frequency of Th17 cells was significantly diminished
      whereas that of Th1 cells was increased in all the lung-associated tissues. Our
      results demonstrate the dynamic and opposing roles of STAT3 during the
      development of Th2 cells from bronchial lymph nodes to the airway and propose the
      need of careful consideration on STAT3-targeting approaches for the treatment of
      lung diseases. 

PMID- 25871879
TI  - Flavonoids derived from liquorice suppress murine macrophage activation by up
      regulating heme oxygenase-1 independent of Nrf2 activation.
AB  - Liquiritigenin (LQG), isoliquiritin (ILQ) and isoliquiritigenin (ILG) are
      flavonoids derived from liquorice and all possess a similar chemical structural
      backbone. In the current study, we found that ILQ and ILG had suppressive effects
      on lipopolysaccharide (LPS)-induced inflammatory responses in murine macrophage
      by suppressing the iNOS and COX-2 proteins and mRNA expression. A mechanistic
      study indicated that the effect was associated with an induction of antioxidant
      and detoxification enzymes, including UGT1A1, NQO1, and heme oxygenase-1 (HO-1)
      mRNA expression. The regulator of these enzymes, nuclear factor-erythroid 2
      related factor 2 (Nrf2), which plays a critical role in LPS-induced inflammatory
      responses, could be activated by ILQ and ILG. Additionally, ILQ and ILG promoted
      Nrf2 signaling activation by inhibiting the Kelch-like ECH-associated protein 1
      (Keap1) and increasing Nrf2 translocation, inducing the expression of these
      antioxidant enzymes. We further found that ILQ and ILG induced HO-1 expression
      independent of Nrf2 expression. With respect to the effect of these compounds on
      NF-kappaB signaling, ILG was found to markedly inhibit IkappaBalpha degradation
      and phosphorylation, while LQG and ILQ had no significant effects. These results
      indicate that there are correlations between the anti-inflammatory responses and
      the chemical structural properties of these flavonoids. 

PMID- 25871877
TI  - APOE4 enhances age-dependent decline in cognitive function by down-regulating an
      NMDA receptor pathway in EFAD-Tg mice.
AB  - BACKGROUND: Alzheimer's disease (AD) causes progressive loss of memory and
      cognition, exacerbated by APOE4, the greatest genetic risk factor for AD. One
      proposed mechanism for apolipoprotein E (apoE) effects on cognition is via NMDAR
      dependent signaling. APOE genotype-specific effects on this pathway were
      dissected using EFAD-transgenic (Tg) mice (5xFAD mice, that over-express human
      amyloid-beta (Abeta) via 5 familial-AD (FAD) mutations, and express human apoE),
      and 5xFAD/APOE-knockout (KO) mice. Previous data from EFAD-Tg mice demonstrate
      age-dependent (2-6 months), apoE-specific effects on the development of Abeta
      pathology. This study tests the hypothesis that apoE4 impairs cognition via
      modulation of NMDAR-dependent signaling, specifically via a loss of function by
      comparison of E4FAD mice with 5xFAD/APOE-KO mice, E3FAD and E2FAD mice. RESULTS:
      Using female E2FAD, E3FAD, E4FAD and 5xFAD/APOE-KO mice aged 2-, 4-, and 6
      months, the Y-maze and Morris water maze behavioral tests were combined with
      synaptic protein levels as markers of synaptic viability. The results demonstrate
      a greater age-induced deficit in cognition and reduction in PSD95, drebrin and
      NMDAR subunits in the E4FAD and 5xFAD/APOE-KO mice compared with E2FAD and E3FAD
      mice, consistent with an apoE4 loss of function. Interestingly, for NMDAR
      mediated signaling, the levels of p-CaMK-II followed this same apoE-specific
      pattern as cognition, while the levels of p-CREB and BDNF demonstrate an apoE4
      toxic gain of function: E2FAD > E3FAD > 5xFAD/APOE-KO > E4FAD. CONCLUSION: These
      findings suggest that compared with E2FAD and E3FAD, E4FAD and 5xFAD/APOE-KO mice
      exhibit enhanced age-induced reductions in cognition and key synaptic proteins
      via down-regulation of an NMDAR signaling pathway, consistent with an apoE4 loss
      of function. However, levels of p-CREB and BDNF, signaling factors common to
      multiple pathways, suggest a gain of toxic function. Publications in this field
      present contradictory results as to whether APOE4 imparts a loss or gain of
      function. As with the results reported herein, the overall effect of APOE4 on a
      given CNS-specific measure will be the product of multiple overlapping
      mechanisms. Thus, caution remains critical in determining whether APOE gene
      inactivation or therapies that correct the loss of positive function related to
      apoE4, are the appropriate therapeutic response.

PMID- 25871880
TI  - Prevalence of rickets-like bone deformities in rural Gambian children.
AB  - The aim of this study was to estimate the burden of childhood rickets-like bone
      deformity in a rural region of West Africa where rickets has been reported in
      association with a low calcium intake. A population-based survey of children aged
      0.5-17.9 years living in the province of West Kiang, The Gambia was conducted in
      2007. 6221 children, 92% of those recorded in a recent census, were screened for
      physical signs of rickets by a trained survey team with clinical referral of
      suspected cases. Several objective measures were tested as potential screening
      tools. The prevalence of bone deformity in children <18.0 years was 3.3%. The
      prevalence was greater in males (M = 4.3%, F = 2.3%, p < 0.001) and in children
      <5.0 years (5.7%, M = 8.3%, F = 2.9%). Knock-knee was more common (58%) than bow
      leg (31%) or windswept deformity (9%). Of the 196 examined clinically, 36 were
      confirmed to have a deformity outside normal variation (47% knock-knee, 53% bow
      leg), resulting in more conservative prevalence estimates of bone deformity: 0.6%
      for children <18.0 years (M = 0.9%, F = 0.2%), 1.5% for children < 5.0 years (M =
      2.3%, F = 0.6%). Three of these children (9% of those with clinically-confirmed
      deformity, 0.05% of those screened) had active rickets on X-ray at the time of
      medical examination. This emphasises the difficulties in comparing prevalence
      estimates of rickets-like bone deformities from population surveys and clinic
      based studies. Interpopliteal distance showed promise as an objective screening
      measure for bow-leg deformity. In conclusion, this population survey in a rural
      region of West Africa with a low calcium diet has demonstrated a significant
      burden of rickets-like bone deformity, whether based on physical signs under
      survey conditions or after clinical examination, especially in boys < 5.0 years.

PMID- 25871881
TI  - Morphology of congenital portosystemic shunts involving the right gastric vein in
      dogs.
AB  - OBJECTIVE: To describe the anatomy of congenital portosystemic shunts involving
      the right gastric vein in dogs. MATERIALS AND METHODS: Retrospective review of a
      consecutive series of dogs managed for congenital portosystemic shunt. RESULTS:
      Twenty-two dogs met the inclusion criteria of a congenital portosystemic shunt
      involving the right gastric vein with recorded intraoperative mesenteric
      portovenography or computed tomography angiography and gross observations at the
      time of surgery. Of these, 20 (91%) had a shunt that entered the pre-hepatic
      caudal vena cava at the level of the epiploic foramen and two (9%) had a shunt
      that entered the post-hepatic caudal vena cava at the level of the diaphragm.
      Shunts entering the pre-hepatic caudal vena cava could be further classified into
      three consistent subdivisions. CLINICAL SIGNIFICANCE: The morphology of each
      shunt type described appeared to be a result of an abnormal communication between
      the left gastric vein and the caudal vena cava, the presence or absence of an
      abnormal communication between the splenic, left gastric and portal veins and the
      subsequent development of preferential blood flow through essentially normal
      portal vessels within the portal venous system. The abnormal communication
      (shunt) was through the left gastric vein and not the right gastric vein, as
      might have been expected. This information may help with surgical planning in
      cases undergoing shunt closure surgery.

PMID- 25871882
TI  - PLA-PEG Coated Multifunctional Imaging Probe for Targeted Drug Delivery.
AB  - Monitoring of drugs in vivo has been recognized as an urgent need for successful
      chemotherapy treatment. However, to find an appropriate tool for this purpose has
      been proved as a great challenge. Here, we report a PLA-PEG coated hollow X-ray
      and upconversion nanophosphor with folic acid as a tumor targeting ligand for a
      novel drug delivery system. In contrast with previously reported PLA-PEG based or
      PLA-PEG coated inorganic nanoparticles, our X-ray and upconversion nanophosphor
      based drug carriers can be used simultaneously as the drug delivery carrier and
      also serve as labels to track the loaded drugs (paclitaxel) by optical
      luminescence excited by X-ray, near-infrared light and magnetic resonance
      imaging. In addition, the hollow space created in our drug carriers dramatically
      increases the amount of loaded drug. Besides, folic acid on the surface of the
      drug loaded nanophosphors enhanced cellular uptake and significantly increased
      the drug efficacy compared with the free drug. We anticipate that these
      multifunctional nanocarriers will result in significant improvement and serve as
      a platform in the field of drug delivery. 

PMID- 25871883
TI  - Nitrogen-Enriched Porous Carbon Coating for Manganese Oxide Nanostructures toward
      High-Performance Lithium-Ion Batteries.
AB  - Manganese oxides are promising high-capacity anode materials for lithium-ion
      batteries (LIBs) yet suffer from short cycle life and poor rate capability.
      Herein, we demonstrate a facile in situ interfacial synthesis of core-shell
      heterostructures comprising nitrogen-enriched porous carbon (pN-C) nanocoating
      and manganese oxide (MnOx) nanotubes. When MnOx/pN-C serves as an anode material
      for LIBs, the pN-C coating plays multiple roles in substantially improving the
      lithium storage performance. In combination with the nanosized structure and
      nanotubular architecture, the MnOx/pN-C nanocomposites exhibit an impressive
      reversible capacity of 1068 mAh g(-1) at 100 mA g(-1), a high-rate delivery of
      361 mAh g(-1) at 8 A g(-1), and a stable cycling retention up to 300 cycles. The
      surface pN-C coating strategy can be extended to design and fabricate various
      metal oxide nanostructures for high-performance LIBs. 

PMID- 25871884
TI  - Effect of Clozapine and Other Antipsychotics on the Level of Platelet-Associated
      Autoantibodies in Children with Schizophrenia: A Longitudinal Follow-Up Study.
AB  - BACKGROUND: Previous studies have demonstrated significantly higher blood titers
      of platelet-associated autoantibodies (PAA) in adult schizophrenia patients
      compared to normal healthy subjects. In addition, young adult schizophrenia
      patients at their early stages of the disorder displayed higher PAA titers than
      older patients with longer duration of the disorder. AIM: To assess
      longitudinally the blood titers of PAA in inpatients with childhood-onset
      schizophrenia at admission, after short- and long-term follow-up, and the
      correlation of these titers with the response to clozapine and other
      antipsychotic treatments. METHODS: Thirty children, age range of 6-12 (mean +/-
      SD: 9.6 +/- 1.5 years), with DSM-IV TR schizophrenia in active psychotic state
      were assessed 3 times: at baseline, after short-term (8-17 weeks; n = 26) and
      after long-term follow-up (33-170 weeks; n = 19). The blood titers of PAA were
      analyzed using ELISA and expressed by a linear optical density (OD) scale. A test
      recording >1.4 OD units was predefined as the positive cutoff value. RESULTS: On
      long-term follow-up, 9 out of the 17 children who were PAA-positive at baseline
      became PAA-negative: 7 already after 2 months of clozapine treatment and 2
      following 3 years of risperidone treatment. Eight children remained PAA-positive
      during the entire study period. There was no significant correlation between the
      clinical improvement (as assessed by change in the Positive and Negative Syndrome
      Scale score) and the alteration in PAA levels (n = 19, r = -0.4, p = 0.088).
      CONCLUSIONS: High rates of positive PAA in COS patients may indicate an active
      autoimmune process in early-onset schizophrenia. It is concluded that PAA may
      serve as a biomarker for the diagnosis of COS, but does not predict the response
      to treatment. A transition to a PAA-negative status does not indicate an
      improvement in psychosis. (c) 2015 S. Karger AG, Basel.

PMID- 25871886
TI  - Synthesis and reactivity of iron complexes with a new pyrazine-based pincer
      ligand, and application in catalytic low-pressure hydrogenation of carbon
      dioxide.
AB  - A novel pincer ligand based on the pyrazine backbone (PNzP) has been synthesized,
      (2,6-bis(di(tert-butyl)phosphinomethyl)pyrazine), tBu-PNzP. It reacts with FeBr2
      to yield [Fe(Br)2(tBu-PNzP)], 1. Treatment of 1 with NaBH4 in MeCN/MeOH gives the
      hydride complex [Fe(H)(MeCN)2(tBu-PNzP)][X] (X = Br, BH4), 2.X. Counterion
      exchange and exposure to CO atmosphere yields the complex cis
      [Fe(H)(CO)(MeCN)(tBu-PNzP)][BPh4] 4.BPh4, which upon addition of Bu4NCl forms
      [Fe(H)(Cl)(CO)(tBu-PNzP)] 5. Complex 5, under basic conditions, catalyzes the
      hydrogenation of CO2 to formate salts at low H2 pressure. Treatment of complex 5
      with a base leads to aggregates, presumably of dearomatized species B, stabilized
      by bridging to another metal center by coordination of the nitrogen at the
      backbone of the pyrazine pincer ligand. Upon dissolution of compound B in EtOH
      the crystallographically characterized complex 7 is formed, comprised of six iron
      units forming a 6-membered ring. The dearomatized species can activate CO2 and H2
      by metal-ligand cooperation (MLC), leading to complex 8, trans-[Fe(PNzPtBu
      COO)(H)(CO)], and complex 9, trans-[Fe(H)2(CO)(tBu-PNzP)], respectively. Our
      results point at a very likely mechanism for CO2 hydrogenation involving MLC. 

PMID- 25871885
TI  - Bisphenol A Exposure during Oocyte Maturation in vitro Results in Spindle
      Abnormalities and Chromosome Misalignment in Bos taurus.
AB  - Bisphenol A (BPA) exposure in humans is widespread, and BPA has been detected in
      a variety of samples including follicular fluid. BPA levels have been found to
      negatively correlate with the developmental potential of oocytes in women
      undergoing in vitro fertilization and to induce meiotic abnormalities
      experimentally in human and mouse models. BPA may detrimentally affect oocyte
      maturation, and different concentrations of exposure can cause various outcomes.
      Because of the importance of oocyte maturation on developmental potential,
      disturbances during this time can significantly impact oocyte viability. Here,
      bovine oocytes were matured in vitro with and without BPA treatment of the media.
      The levels of BPA taken up by the oocytes were much lower than the initial
      exposure. Medium treatment with 30 ng/ml resulted in an average of 2.48 ng/ml BPA
      measured in mature oocytes. These oocytes exhibited decreased maturation and
      increased incidence of spindle abnormalities. Only 57.4% of oocytes exposed to 30
      ng/ml BPA reached maturity compared to 72.4% of controls (p < 0.05). Mature
      oocytes following BPA exposure displayed increased abnormal spindle morphology
      (67.9%) and chromosome dispersal (60%) compared to all other groups analyzed (p <
      0.05). Thus, exposure to BPA during in vitro oocyte maturation has the potential
      to decrease oocyte quality.

PMID- 25871887
TI  - TCF12 microdeletion in a 72-year-old woman with intellectual disability.
AB  - Heterozygous mutations in TCF12 were recently identified as an important cause of
      craniosynostosis. In the original series, 14% of patients with a mutation in
      TCF12 had significant developmental delay or learning disability. We report on
      the first case of TCF12 microdeletion, detected by array-comparative genomic
      hybridization, in a 72-year-old patient presenting with intellectual deficiency
      and dysmorphism. Multiplex ligation-dependent probe amplification analysis
      indicated that exon 19, encoding the functionally important basic helix-loop
      helix domain, was included in the deleted segment in addition to exon 20. We
      postulate that the TCF12 microdeletion is responsible for this patient's
      intellectual deficiency and facial phenotype.

PMID- 25871888
TI  - CRISPR-Cas9 Based Genome Engineering: Opportunities in Agri-Food-Nutrition and
      Healthcare.
AB  - Recently developed strategies and techniques that make use of the vast amount of
      genetic information to perform targeted perturbations in the genome of living
      organisms are collectively referred to as genome engineering. The wide array of
      applications made possible by the use of this technology range from agriculture
      to healthcare. This, along with the applications involving basic biological
      research, has made it a very dynamic and active field of research. This review
      focuses on the CRISPR system from its discovery and role in bacterial adaptive
      immunity to the most recent developments, and its possible applications in
      agriculture and modern medicine. 

PMID- 25871889
TI  - National study of chronic disease self-management: 6-month and 12-month findings
      among cancer survivors and non-cancer survivors.
AB  - OBJECTIVE: This study examined the applicability of the Stanford Chronic Disease
      Self-Management Program (CDSMP) for cancer survivors and compared outcomes among
      cancer survivors and participants with other chronic diseases (non-cancer
      survivors). METHODS: Participants were older adults (n = 1170) enrolled in the
      National Study of CDSMP. Detailed information about physical and psychosocial
      health status and health and healthcare behaviors was collected from participants
      (n = 116 cancer survivors and n = 1054 non-cancer survivors) via self-report
      before CDSMP participation and at 6-month and 12-month follow-ups. Linear and
      generalized linear mixed models were used to assess baseline-to-6-month and
      baseline-to-12-month changes. RESULTS: Among cancer survivors, general health,
      depression, and sleep significantly improved from baseline to 6 months. These
      significant changes were sustained at 12 months. Communication with physician,
      medication compliance, pain, days in poor physical health, days in poor mental
      health, and days kept from usual activities and physical activity also improved
      significantly from baseline to 12 months. Among non-cancer survivors, all
      outcomes except medication compliance and stress improved significantly from
      baseline to 6 months. At 12 months, medication compliance also improved
      significantly. CONCLUSIONS: Findings suggest that participation in CDSMP, an
      evidence-based chronic disease self-management intervention not specifically
      tailored for cancer survivorship, may significantly improve physical and
      psychosocial health status and key health and healthcare behaviors among cancer
      survivors. Additional research is needed to elucidate cancer survivors' unique
      needs and examine the benefits of tailored versions of CDSMP. Nevertheless,
      CDSMP, available at scale nationally and internationally, is a promising
      intervention for cancer survivors and should be considered a valuable component
      of survivorship care.

PMID- 25871890
TI  - Treatment with Recombinant Human Insulin-Like Growth Factor-1 in Severe Primary
      IGF Deficiency and Beyond.

PMID- 25871891
TI  - Cybervictimization of Young People With an Intellectual or Developmental
      Disability: Risks Specific to Sexual Solicitation.
AB  - BACKGROUND: Studies demonstrate that youth are vulnerable to online sexual
      solicitation. However, no study has estimated this risk for youth diagnosed with
      an intellectual or developmental disability (IDD). METHODS: A literature review
      of the risk factors associated with online sexual solicitation in youths was done
      using electronic databases, such as PsychInFO, ERIC, MEDLINE and Scopus. RESULTS:
      Fifty-seven published papers were found relevant. However, only two pertained to
      the population with IDD. Sexual and physical abuse, social isolation, loneliness,
      depression, and chatting were found to increase the risk of being prey to sexual
      solicitation on the Internet. Many of these risk factors are even more prevalent
      in youth with IDD than in the general population. CONCLUSION: Recommendations are
      made for future research to help understand and prevent sexual cybersolicitation.

PMID- 25871892
TI  - Live-Cell STED Microscopy with Genetically Encoded Biosensor.
AB  - Of the various super-resolution techniques, stimulated emission depletion (STED)
      microscopy achieves the best temporal resolution at high spatial resolution,
      enabling live-cell imaging beyond the diffraction limit. However, STED and most
      other super-resolution imaging methods utilize a particular type of information
      extractable from the raw data, namely the positions of fluorophores. To expand on
      the use of super-resolution techniques, we report here the live-cell STED
      microscopy of a dynamic biosensor. Using the fluorescent H2O2 sensor HyPer2 for
      subdiffraction imaging, we were able not only to image filaments with superior
      resolution by localizing emission but also to trace H2O2 produced within living
      cell by monitoring brightness of the probe. STED microscopy of HyPer2
      demonstrates potential utility of FP-based biosensors for super-resolution
      experiments in situ and in vivo. 

PMID- 25871893
TI  - Characteristics, expectations and needs of the dutch endometriosis society
      members.
AB  - BACKGROUND/AIM STUDY QUESTION: Endometriosis is associated with a significant
      reduction in the quality of life and higher depression and anxiety rates. The
      Dutch Endometriosis Society (ES) was founded to increase the recognition and
      knowledge in patients and health care professionals, stimulate research and
      improve care. This study was conducted to explore the characteristics of the
      members and evaluate their needs and expectations. METHODS: A descriptive
      questionnaire-based survey was conducted among all members of the ES. The
      response rate was 51% (n = 571). RESULTS: ES members appear to be highly educated
      women with a wide variety of endometriosis-related symptoms resulting in
      considerable restrictions in daily life. Information transmission was considered
      the main aim of ES (97%), whereas 56% expected social support, and 38% expected
      advocacy. The majority (71%) reported an improvement in their quality of life
      after contact with the ES. CONCLUSION: The results of this study underline
      patients' primary quest for information about endometriosis. Patient support
      groups such as ES can fulfil a useful role in disseminating knowledge from
      medical professionals to those suffering a chronic illness, resulting in a
      greater understanding and ultimately increasing their quality of life.

PMID- 25871896
TI  - Essential anatomy of the head and neck: the complete Delphi Panel list.

PMID- 25871894
TI  - Is the BFM Regimen Feasible for the Treatment of Adult Acute Lymphoblastic
      Leukemia? A Retrospective Analysis of the Outcomes of BFM and Hyper-CVAD
      Chemotherapy in Two Centers.
AB  - Multiple induction regimens have been developed for adult patients with acute
      lymphoblastic leukemia (ALL). However, there have been no prospective randomized
      trials that directly compare these regimens. In this study, we wanted to evaluate
      the outcome of 50 adult ALL patients treated with BFM (i.e. Berlin-Frankfurt
      Munster, n = 20) and hyper-CVAD (n = 30) protocols between March 2006 and October
      2012. The median age was 25 years in the BFM group and 30.5 years in the hyper
      CVAD group with a male/female ratio of 15:5 and 17:13, respectively. Forty-five
      percent of the patients in the BFM group and 30.3% in the hyper-CVAD group were
      <25 years old. The majority of cases were B cell in origin (80% in the BFM group
      and 70% in the hyper-CVAD group). Complete remission after induction therapy was
      achieved in 95 and 96% of the patients, respectively. The median follow-up time
      was 37 months. The 5-year survival rate was higher in the BFM group than in the
      hyper-CVAD group (59 vs. 34%). There were also no complications which could cause
      a delay during the hyper-CVAD regimen. Both chemotherapies were well tolerated.
      None of the patients died from drug-related toxicity. Only mild liver enzyme
      elevations were seen as toxicity in the BFM group; these did not cause any delay
      in therapy. The BFM regimen seems to be feasible for adult patients with ALL in
      terms of tolerability and efficacy, especially in young adults.

PMID- 25871898
TI  - A 5-Year Retrospective Review of Primary Palatoplasty Cases Utilizing an
      Acellular Collagen Interpositional Graft.
AB  - PURPOSE: Multiple palatoplasty techniques have been developed, but a technique
      involving a partial 2-layer soft tissue closure of the posterior hard palate and
      nasal floor and a 3-layer soft tissue closure of the soft palate with
      reorientation of the levator and tensor veli muscles across the midline has been
      the gold standard for cleft repair. This report describes a series of primary
      palatoplasties reconstructed with a middle layer of acellular collagen membrane
      that aided in maintaining closure between the oral and nasal cavities without the
      development of an oronasal fistula. MATERIALS AND METHODS: An acellular collagen
      membrane was placed between the muscular layer and the oral mucosa during primary
      palatoplasty. Six patients with primary cleft palatoplasty were identified and
      followed for 1 year (patient 1, a 10-month-old boy; patient 2, a 12-month-old
      girl; patient 3, a 12-month-old girl; patient 4, a 6-year-old boy; patient 5, a
      12-month-old girl; and patient 6, an 18-month-old girl). RESULTS: At 1 year, no
      oronasal fistulas had developed where augmentation with the acellular collagen
      membrane was used. CONCLUSIONS: The use of an acellular collagen graft to aid in
      the 3-layer closure of primary palatoplasty surgery is a very effective strategy
      in primary and secondary healing and in preventing oronasal fistulation. The risk
      associated with the use of acellular collagen membranes appears nonexistent.

PMID- 25871899
TI  - Life-Threatening Oral Bleed-A Rare Presentation of Hereditary Hemorrhagic
      Telangiectasia.
AB  - Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder of
      fibrovascular tissues. Patients with HHT often develop life-threatening bleeds
      from telangiectasias in the nasal or gastrointestinal mucosa or from visceral
      arteriovenous malformations. Recurrent oral bleeds are rare presentations in
      these patients and are seldom reported. This report describes a rare case of 72
      year-old man with a known history of HHT who presented with a recurrent life
      threatening oral bleed from telangiectasia of the palate and reviews the
      literature for current trends of medical and dental management. This study is an
      effort to draw the attention of oral physicians and surgeons to such drastic
      complications of the disease and various current treatment modalities. 

PMID- 25871900
TI  - Is There a Difference in Stability or Neurosensory Function Between Bilateral
      Sagittal Split Ramus Osteotomy and Intraoral Vertical Ramus Osteotomy for
      Mandibular Setback?
AB  - PURPOSE: Bilateral sagittal split ramus osteotomy (BSSO) and intraoral vertical
      ramus osteotomy (IVRO) are used for mandibular setbacks. The purpose of this
      study was to determine differences in skeletal stability and neurosensory
      disturbance (NSD) of the mental nerve after mandibular setback using these
      operations. MATERIALS AND METHODS: A systematic review and meta-analysis on these
      topics was performed. An electronic search of several databases with specific
      keywords, a reference search, and a manual search from database inception to
      December 2014 was performed with inclusion criteria of clinical human studies,
      randomized controlled trials (RCTs), controlled clinical trials (CCTs), and
      retrospective studies, with the predictor variable being BSSO or IVRO after
      mandibular setback surgery. The outcome variables of horizontal and vertical
      relapse using cephalometrics and NSD using trigeminal somatosensory-evoked
      potential and subjective tests were statistically analyzed. RESULTS: The initial
      PubMed search identified 716 studies of which 13 met the inclusion criteria-4
      RCTs, 3 CCTs, and 6 retrospective studies. No statistically significant
      difference was found between the 2 groups regarding horizontal skeletal
      stability, but the BSSO group had more stability in the vertical dimension (P =
      .02). There was a statistically significant difference between BSSO and IVRO with
      regard to NSD of the inferior alveolar nerve (IAN; P = .001). CONCLUSION: The
      results of this meta-analysis suggest that BSSO and IVRO have good stability when
      used to set back the mandible. Furthermore, the results showed that IVRO
      statistically decreased the incidence of NSD of the IAN after mandibular setback
      surgery compared with BSSO.

PMID- 25871901
TI  - Nodal Yield: Is it a Prognostic Factor for Head and Neck Squamous Cell Carcinoma?
AB  - PURPOSE: The prognostic value of lymph node yield (LNY) in head and neck squamous
      cell carcinoma (HNSCC) remains controversial. The aim of this study was to
      explore whether LNY influences locoregional recurrence risk and prognosis in
      patients with HNSCC. PATIENTS AND METHODS: This retrospective cohort study
      reviewed the records of 1,546 eligible patients with HNSCC who were treated at
      Beijing Stomatological Hospital, Capital Medical University, from July 1989 to
      October 2012. The predictor variable was LNY. The main outcome assessment
      parameters were 2-year neck recurrence rate (NRR) and 5-year disease-specific
      survival (DSS). All statistical analyses were performed using SPSS 19.0 for
      Windows. RESULTS: The mean and median LNY per neck dissection were 25.1 and 23.0,
      respectively. There was no significant association between LNY quartile and 2
      year NRR in the pN0 (P = .397) or pN(+) (P = .335) group. Univariate analysis of
      the pN0 group showed no significant association between LNY and 5-year DSS (P =
      .676). The analysis of patients with pN(+) who underwent only selective neck
      dissection showed a significantly higher prognostic risk with an increased LNY
      (LNY <19 vs >=34, 79.2% vs 59.4%; P = .014). Interestingly, in the comprehensive
      neck dissection subgroup, there was an obvious tendency for patients with a high
      LNY to have a better 5-year DSS than those with a low LNY (LNY <19 vs >=34, 55.6%
      vs 76.4%; P = .021). Multivariate analysis showed that LNY was not an independent
      predictive factor for 2-year NRR or 5-year DSS. CONCLUSIONS: LNY is statistically
      associated with the risk of lymph node metastasis, but does not predict neck
      recurrence. The exact prognostic value of LNY for patients with pN(+) remains
      unknown, and further study is needed to validate the present findings.

PMID- 25871902
TI  - Application of Thinned Anterolateral Thigh Flap for the Reconstruction of Head
      and Neck Defects.
AB  - PURPOSE: To evaluate the feasibility and reconstructive efficacy of the thinned
      anterolateral thigh (ALT) flap for the reconstruction of head and neck defects.
      PATIENTS AND METHODS: A retrospective review was performed of 43 patients who had
      undergone reconstruction of head and neck defects with a thinned ALT flap from
      January 2009 through December 2013 at the Second Xiangya Hospital. The methods
      for flap thinning and defect reconstruction and reconstructive efficacy are
      reported. RESULTS: The flaps were 5 cm * 7 cm to 9 cm * 14 cm, and all were
      harvested from a single cutaneous perforator. Postoperatively, 40 flaps survived
      completely and 3 flaps experienced partial necrosis. Venous compromise occurred
      in 2 cases, both of which were salvaged after operative exploration. Of the 43
      donor sites, 41 were closed directly and resulted in only linear scars, and 2
      were closed using full-thickness skin grafts because the defect was larger. All
      the patients were followed for approximately 6 to 36 months, and they were
      satisfied with the esthetic and functional results of the donor and recipient
      sites after reconstruction. CONCLUSION: With the high success rate of flap
      transplantation, satisfactory functional and esthetic results, and lower
      complication rates at the donor and recipient sites, the use of thinned ALT flaps
      can be a good choice for the reconstruction of head and neck defects in obese
      patients.

PMID- 25871903
TI  - Surgical Therapy for Bisphosphonate-Related Osteonecrosis of the Jaw: Six-Year
      Experience of a Single Institution.
AB  - PURPOSE: Bisphosphonates are drugs commonly used to treat osteoporosis,
      hypercalcemia of malignancy, and bone metastases. In some cases, its
      administration has been associated with osteonecrosis of the jaws. The management
      of medication-related osteonecrosis of the jaw (MRONJ) has not been completely
      elucidated, and its treatment can vary from no or limited surgery to more
      extensive surgery. The objective of the present study was to evaluate the
      efficacy of surgical therapy for patients presenting with MRONJ. PATIENTS AND
      METHODS: A retrospective study was conducted that evaluated all MRONJ cases
      resulting from bisphosphonate use and treated by surgery from 2006 to 2012. All
      patients underwent surgery under general anesthesia. RESULTS: A total of 33
      patients with 46 MRONJ sites were evaluated. Most of the patients were women,
      with an age range of 39 to 83 years (mean 65.6 +/- 10.6). Complete healing of the
      MRONJ region was observed in 40 of the 46 sites (87%), with partial improvement
      (symptom control and reduction of the exposed bone area) observed in 3 sites
      (6.5%), for a 93.5% clinical benefit rate. Of the remaining regions, 2 showed no
      significant changes, and 1 presented with a worse aspect compared with the
      patient's preoperative condition. Such cases were located in the posterior
      mandible region. The number of applications and type of bisphosphonate did not
      influence the treatment response. CONCLUSION: The surgical approach to treating
      MRONJ showed a high rate of clinical control. Therefore, surgery should be
      considered as a therapy for some cases of this condition.

PMID- 25871904
TI  - Dimensional Changes of the Upper Lip Using Dermis Fat Graft for Lip Augmentation.
AB  - PURPOSE: Lip augmentation is a facial cosmetic procedure used to augment a thin
      upper lip or correct a lip deficiency. The aim of this study was to evaluate
      dimensional changes 12 months after dermis fat grafting along the centerpiece of
      the upper lip. MATERIALS AND METHODS: In this prospective cohort study, a strip
      dermis fat graft was harvested from various sites, namely the presacral, pre
      abdominal, and suprapubic regions, and used for augmentation of the upper lip.
      Then, it was placed in a pocket prepared in the center of the upper lip near the
      border between the wet and dry areas using a cannula. Upper lip vermilion show
      and lip projection were evaluated before and 12 months after augmentation using
      preoperative and postoperative photographs and digital imaging software. Age and
      gender were variable factors of the study. Changes of vermilion show and lip
      projection were considered outcomes of the study. Paired t test was used to
      compare vermilion show and lip projection before and 12 months after grafting.
      RESULTS: Fifteen patients were studied. No serious complication arose during the
      study and all patients were satisfied. The mean change for vermilion show was
      1.73 +/- 0.74 mm and that for lip projection was 2.33 +/- 0.68 mm. Quantitative
      analysis showed that vermilion show and projection of the upper lip improved
      significantly (P < .001). CONCLUSION: Augmentation of the lip with dermis fat
      grafting can be a safe and reliable method to treat thin lips.

PMID- 25871905
TI  - Assessment of hepatoprotective potential of N. indicum leaf on haloalkane
      xenobiotic induced hepatic injury in Swiss albino mice.
AB  - CCl4 is a potent environmental toxin which cause liver damage through free
      radical mediated inflammatory processes. In this study, hepatoprotective capacity
      of Nerium indicum leaf extract (NILE) was evaluated on CCl4 induced acute
      hepatotoxicity in murine model. Animals were divided into 5 groups and treated as
      following: control group (received only normal saline), CCl4 group (received only
      CCl4), silymarin group (received CCl4 and 100mg/kg silymarin), NILE low group
      (received CCl4 and 50mg/kg NILE) and NILE high group (received CCl4 and 200mg/kg
      NILE). After 10 consecutive days of treatment, the levels of hepatic biochemical
      markers, malondialdehyde (MDA) content, peroxidase and catalase activities were
      measured as well as histopathological study was performed. Furthermore, liver
      explant cultures were set up as following: control (no treatment), CCl4 group
      (contained 25 MUl/ml CCl4), silymarin group (contained 25 MUl/ml CCl4 and 100
      MUg/ml silymarin), NILE low group (contained 25 MUl/ml CCl4 and 25 MUg/ml NILE)
      and NILE high group (contained 25 MUl/ml CCl4 and 100 MUg/ml NILE). Hepatic
      transaminases and phosphatases, tumor necrosis factor-alpha (TNF-alpha)
      expression, nitric oxide (NO) release and cell viability were studied on the
      explant cultures. Phytochemical fingerprinting of NILE was performed by gas
      chromatography-mass spectrometry (GC-MS). The results showed that the biochemical
      parameters were overexpressed due to CCl4 administration, which were
      significantly normalized by NILE treatment. The findings were further supported
      by histopathological evidences showing less hepatocellular necrosis, inflammation
      and fibrosis in NILE and silymarin treated groups, compared to CCl4 group. GC-MS
      analysis revealed presence of different bioactive phytochemicals with
      hepatoprotective and antioxidant properties. Therefore, the present study
      indicate that NILE possesses potent hepatoprotective capacity to ameliorate
      haloalkane xenobiotic induced injured liver in murine model.

PMID- 25871907
TI  - Octaethyl-1,3-oxazinochlorin: A beta-Octaethylchlorin Analogue Made by Pyrrole
      Expansion.
AB  - Treatment of the oxime of octaethyloxochlorin 4, available from
      octaethylporphyrin 3, under Beckmann conditions provided not the expected lactam,
      but octaethyl-1,3-oxazinochlorin 8, in which a pyrrole moiety of the parent
      oxochlorin was expanded by an oxygen atom to an 1,3-oxazinone moiety. Its
      mechanism of formation was demonstrated to occur along an "abnormal Beckmann"
      pathway, followed by intramolecular ring closure and hydrolysis. The work expands
      the methodologies known to convert octaethylporphyrin to pyrrole-modified
      porphyrin analogues. 

PMID- 25871906
TI  - A Sex-Specific MicroRNA-96/5-Hydroxytryptamine 1B Axis Influences Development of
      Pulmonary Hypertension.
AB  - RATIONALE: Females are predisposed to pulmonary arterial hypertension (PAH);
      evidence suggests that serotonin, mutations in the bone morphogenetic protein
      receptor (BMPR) II gene, and estrogens influence development of PAH. The 5
      hydroxytryptamine 1B receptor (5-HT1BR) mediates human pulmonary artery smooth
      muscle cell (hPASMC) proliferation. OBJECTIVES: We aimed to determine whether
      selected microRNAs (miRNAs) expressed in PASMCs are influenced by sex, BMPR-II
      mutations, and estrogens, and contribute to PASMC proliferation in PAH. METHODS:
      Expression levels of miRNAs targeting genes related to PAH, estrogen, and
      serotonin were determined by quantitative RT-PCR in hPASMCs and mouse PASMCs
      harboring a heterozygous mutation in BMPR-II (BMPR-II(R899X+/-) PASMCs). miRNA-96
      targets 5-HT1BR and was selected for further investigation. miRNA target
      validation was confirmed by luciferase reporter assay. Precursor miRNA-96 was
      transfected into hPASMCs to examine effects on proliferation and 5-HT1BR
      expression. The effect of a miRNA-96 mimic on the development of hypoxic
      pulmonary hypertension in mice was also assessed. MEASUREMENTS AND MAIN RESULTS:
      miRNA-96 expression was reduced in BMPR-II(R899X+/-) PASMCs from female mice and
      hPASMCs from female patients with PAH; this was associated with increased 5-HT1BR
      expression and serotonin-mediated proliferation. 5-HT1BR was validated as a
      target for miRNA-96. Transfection of precursor miRNA-96 into hPASMCs reduced 5
      HT1BR expression and inhibited serotonin-induced proliferation. Restoration of
      miRNA-96 expression in pulmonary arteries in vivo via administration of an miRNA
      96 mimic reduced the development of hypoxia-induced pulmonary hypertension in the
      mouse. CONCLUSIONS: Increased 5-HT1BR expression may be a consequence of
      decreased miRNA-96 expression in female patient PASMCs, and this may contribute
      to the development of PAH.

PMID- 25871908
TI  - Role of actin filaments in fusopod formation and osteoclastogenesis.
AB  - Cell fusion process is a critical, rate-limiting step in osteoclastogenesis but
      the mechanisms that regulate fusopod formation are not defined. We characterized
      fusopod generation in cultured pre-osteoclasts derived from cells stably
      transfected with a plasmid that expressed a short, actin filament binding peptide
      (Lifeact) fused to mEGFP that enables localization of actin filaments in living
      cells. Fusion was initiated at fusopods, which are cell extensions of width >2
      MUm and that are immunostained for myosin-X at the extension tips. Fusopods
      formed at the leading edge of larger migrating cells and from the tail of
      adjacent smaller cells, both of which migrated in the same direction. Staining
      for DC-STAMP was circumferential and did not localize to cell-cell fusion sites.
      Compared with wild-type cells, monocytes null for Rac1 exhibited 6-fold fewer
      fusopods and formed 4-fold fewer multinucleated osteoclasts. From time-lapse
      images we found that fusion was temporally related to the formation of coherent
      and spatially isolated bands of actin filaments that originated in cell bodies
      and extended into the fusopods. These bands of actin filaments were involved in
      cell fusion after approaching cells formed initial contacts. We conclude that the
      formation of fusopods is regulated by Rac1 to initiate intercellular contact
      during osteoclastogenesis. This step is followed by the tightly regulated
      assembly of bands of actin filaments in fusopods, which lead to closure of the
      intercellular gap and finally, cell fusion. These novel, actin-dependent
      processes are important for fusion processes in osteoclastogenesis.

PMID- 25871909
TI  - Atrial fibrillation: recent advances in understanding the role of microRNAs in
      atrial remodeling with an electrophysiological overview.
AB  - Atrial fibrillation (AF) is a highly prevalent condition associated with
      pronounced cardiovascular-related morbidity, mortality and socioeconomic burden.
      It accounts for more hospitalization days than does any other arrhythmia. This
      article reviews the basic electrophysiology of AF, electrical and structural
      remodeling in AF and recent advances in understanding the molecular mechanisms of
      AF in relation to specific microRNAs. This paper also reviews the potential role
      of microRNAs as novel therapeutic targets as well as biomarkers in the management
      of AF. AF shows characteristics typical of altered electrophysiology that promote
      ectopic activity and facilitate reentry, thereby contributing to the progression
      from short paroxysmal AF to a persistent, permanent form via atrial remodeling,
      even in the absence of progressive underlying heart disease. MicroRNAs have been
      suggested to influence the development of AF by regulating gene expression at the
      post-transcriptional level. Increasing evidence has identified various microRNA
      modifications and their impacts on AF initiation and maintenance through
      electrical and structural remodeling. The discovery of specific microRNAs as
      novel therapeutic targets and some experimental evidence implicating microRNAs as
      potential molecular diagnostic markers have had a significant impact on the
      diagnosis and management of AF and demand further research.

PMID- 25871910
TI  - Association between Blood Level of Plasma Oxytocin and Novelty Seeking among
      Methadone-Maintained Heroin Users.
AB  - BACKGROUND: Oxytocin interacts with the dopaminergic system, which plays a role
      in addiction behaviors. The association between oxytocin and addiction was
      confirmed in animal studies. Novelty seeking is one of the predictors and
      indicators of drug addiction. The aim of the present study was to probe the
      association between oxytocin and novelty seeking. METHODS: The study was
      conducted in a methadone maintenance therapy clinic of a medical center in
      Taiwan; 77 patients with heroin dependency were enrolled. Plasma oxytocin was
      measured using an ELISA kit. Novelty seeking was measured using an established
      instrument (the novelty seeking subscale of the Tridimensional Personality
      Questionnaire). RESULTS: A significant negative association (rho = -0.27, p =
      0.02; r = -0.34, p = 0.003) between the blood level of plasma oxytocin and
      novelty seeking was found. This association was significant after controlling the
      effects of perceived social support and the dosage of methadone (r = -0.32, p =
      0.006). CONCLUSION: The negative association between oxytocin and novelty seeking
      may provide insight into future treatments for addiction. (c) 2015 S. Karger AG,
      Basel.

PMID- 25871912
TI  - The presence of eye defects in patients with Turner syndrome is irrespective of
      their karyotype.
AB  - OBJECTIVE: Published data on eye disorders in patients with Turner syndrome (TS)
      are limited. We aimed to evaluate the prevalence of eye disorders in patients
      with TS and assess the association with patient karyotype. DESIGN: Cross
      sectional, observational study. PATIENTS: Eighty-two patients with TS.
      MEASUREMENTS: We evaluated visual acuity (distance and proximity), intraocular
      pressure, optic system refraction, orthoposition, frontal eye segment, the eye
      fundus and colour vision. For eye fundus abnormalities, we conducted ultrasound
      examinations, visual field evaluations and fluorescein angiography. We
      statistically tested the association between the prevalence of eye disorders and
      karyotype. RESULTS: 50 (61%) patients had monosomy X; 9 (11%) had mosaicism with
      a normal 46,XX line; 21 (26%) had structural aberrations; and 2 patients (2%) had
      other chromosomal abnormalities. Eye disorders were diagnosed in 43 (52%)
      patients, with 29 (35%) patients having multiple eye defects. Defects related to
      impaired vision were the most common (44%), followed by strabismus (21%), changes
      in the posterior eye segment (6%), red-green colour deficiency (5%), changes in
      the anterior eye segment (5%) and nystagmus (4%). Amblyopia was diagnosed in 13
      patients (16%). The most common combinations of ophthalmological defects were
      hypermetropia and astigmatism with or without other eye problems (12 patients).
      We found no association between the presence of eye defects and karyotype.
      CONCLUSIONS: Detection of eye abnormalities is necessary in all patients directly
      after being diagnosed with TS to prevent irreversible deterioration of eye
      function and permanent poor vision. All girls with TS, irrespective of their
      karyotype, should be referred to an ophthalmologist.

PMID- 25871913
TI  - Safety and efficacy of fondaparinux for prophylaxis of venous thromboembolism
      after colorectal cancer resection: a propensity score matched analysis.
AB  - BACKGROUND/AIMS: The aim of this study was to examine the safety and efficacy of
      fondaparinux (FPX) for venous thromboembolism (VTE) prophylaxis after colorectal
      cancer surgery. METHODS: Records of 953 patients with colorectal cancer who
      underwent resection between 2006 and 2013 were reviewed. Patients were divided
      into two groups: the FPX group (n = 362), treated with subcutaneous FPX plus
      intermittent pneumatic compression (IPC) and the IPC group (n = 591), treated
      with IPC alone. The incidence of symptomatic VTE, major bleeding, minor bleeding,
      and other postoperative complications were compared using propensity score
      matching. RESULTS: Symptomatic VTE occurred only in one patient (0.2%) in the IPC
      group. In the FPX group, the incidence of major and minor bleeding was 0.55% (2
      of 362) and 9.4% (34 of 362), respectively. After propensity score matching,
      there were no differences between the two groups in the incidence of symptomatic
      VTE, major bleeding, and other common postoperative complications. Only the
      incidence of minor bleeding was significantly higher in the FPX group compared to
      the IPC group. CONCLUSION: FPX is potentially an effective form of VTE
      prophylaxis; it is safe in terms of both postoperative bleeding and other common
      complications after colorectal cancer surgery.

PMID- 25871911
TI  - Genomic alterations in DNA repair and chromatin remodeling genes in estrogen
      receptor-positive metastatic breast cancer patients with exceptional responses to
      capecitabine.
AB  - We analyzed the genomic and phosphoproteomic profiles of breast cancer tissue
      obtained from six patients with estrogen receptor (ER)-positive, HER2-negative
      metastatic breast cancer who had highly durable (>= 5 years) and, in some cases,
      ongoing clinical responses with capecitabine. Formalin-fixed, paraffin-embedded
      tissue samples from patients' primary (n = 4) or metastatic (n = 2) breast
      cancers were utilized for targeted next-generation sequencing and reversed phase
      protein microarray. Two patients received capecitabine monotherapy. Four patients
      received capecitabine in combination with paclitaxel; three of these continued
      single-agent capecitabine after stopping paclitaxel. Capecitabine was
      discontinued for progressive disease after a mean of 66 months in four patients
      (range 54-86 months), and two patients remain on therapy, having received
      capecitabine for >91 months and >122 months, respectively. Three patients'
      cancers (50%) had likely functional alterations in DNA repair and chromatin
      remodeling genes, while three other patients' cancers had variants of unknown
      significance in these pathways. Mutations in PIK3CA, amplifications of FGFR1 or
      ZNF703, or phosphorylation of HER family receptors and their downstream proteins
      did not preclude exceptional responses to capecitabine. None of the patients'
      tumors harbored TP53 or PTEN mutations. Four of the patients had breast cancer
      tissue available for PTEN immunohistochemistry, and all four patients' cancers
      were positive for PTEN. These surprising findings in a group of phenotypically
      similar patients with ER-positive, endocrine therapy-pretreated, HER2-negative
      metastases, are supported by preclinical data showing that sensitivity to 5
      fluorouracil is enhanced by deficiencies in chromatin remodeling and homologous
      recombination genes. Our findings suggest that mutations that inactivate
      homologous recombination and/or chromatin remodeling genes within ER-positive,
      HER2-negative breast cancers may predict for highly durable responses to
      capecitabine.

PMID- 25871914
TI  - Multidimensional Effects in Nonadiabatic Statistical Theories of Spin-Forbidden
      Kinetics: A Case Study of (3)O + CO -> CO2.
AB  - The appropriateness of treating crossing seams of electronic states of different
      spins as nonadiabatic transition states in statistical calculations of spin
      forbidden reaction rates is considered. We show that the spin-forbidden reaction
      coordinate, the nuclear coordinate perpendicular to the crossing seam, is coupled
      to the remaining nuclear degrees of freedom. This coupling gives rise to
      multidimensional effects that are not typically included in statistical
      treatments of spin-forbidden kinetics. Three qualitative categories of
      multidimensional effects may be identified: static multidimensional effects due
      to the geometry-dependence of the local shape of the crossing seam and of the
      spin-orbit coupling, dynamical multidimensional effects due to energy exchange
      with the reaction coordinate during the seam crossing, and nonlocal (history
      dependent) multidimensional effects due to interference of the electronic
      variables at second, third, and later seam crossings. Nonlocal multidimensional
      effects are intimately related to electronic decoherence, where electronic
      dephasing acts to erase the history of the system. A semiclassical model based on
      short-time full-dimensional trajectories that includes all three multidimensional
      effects as well as a model for electronic decoherence is presented. The results
      of this multidimensional nonadiabatic statistical theory (MNST) for the (3)O + CO
      -> CO2 reaction are compared with the results of statistical theories employing
      one-dimensional (Landau-Zener and weak coupling) models for the transition
      probability and with those calculated previously using multistate trajectories.
      The MNST method is shown to accurately reproduce the multistate decay-of-mixing
      trajectory results, so long as consistent thresholds are used. The MNST approach
      has several advantages over multistate trajectory approaches and is more suitable
      in chemical kinetics calculations at low temperatures and for complex systems.
      The error in statistical calculations that neglect multidimensional effects is
      shown to be as large as a factor of 2 for this system, with static
      multidimensional effects identified as the largest source of error. 

PMID- 25871915
TI  - Serum sodium levels and patient outcomes in an ambulatory clinic-based chronic
      kidney disease cohort.
AB  - BACKGROUND: Chronic kidney disease (CKD) patients are prone to both hypo- and
      hypernatremia. Little has been published on the epidemiology of hypo- and
      hypernatremia in ambulatory patients with non-dialysis CKD. METHODS: Data
      collected in two contemporaneous CKD cohort studies, the Renal Research Institute
      (RRI)-CKD study (n = 834) and the Study of Treatment of Renal Insufficiency: Data
      and Evaluation (STRIDE) (n = 1,348) were combined and analyzed to study the
      association between serum sodium (Na(+)) and clinical outcomes. RESULTS: Baseline
      estimated glomerular filtration rate (eGFR) and Na(+) were 26 +/- 11 ml/min/1.73
      m(2) and 140.2 +/- 3.4 mEq/l, respectively. The prevalence of Na(+) <=135 mEq/l
      and >=144 mEq/l was 6 and 16%, respectively. Higher baseline Na(+) was
      significantly associated with male sex, older age, systolic blood pressure, BMI,
      serum albumin, presence of heart failure, and lower eGFR. The risk of end-stage
      renal disease (ESRD) was marginally significantly higher among patients with
      Na(+) <=135 mEq/l, compared with 140< Na(+) <144 mEq/l (referent), in time
      dependent models (adjusted hazard ratio, HR = 1.52, p = 0.06). Mortality risk was
      significantly greater at 135< Na(+) <=140 mEq/l (adjusted HR = 1.68, p = 0.02)
      and Na(+) >=144 mEq/l (adjusted HR = 2.01, p = 0.01). CONCLUSION: CKD patients
      with Na(+) <=135 mEq/l were at a higher risk for progression to ESRD, whereas
      both lower and higher Na(+) levels were associated with a higher risk of
      mortality. While caring for CKD patients, greater attention to serum sodium
      levels by clinicians is warranted and could potentially help improve patient
      outcomes.

PMID- 25871916
TI  - Hospital outcomes and economic costs from poisoning cases in Illinois.
AB  - CONTEXT: Since 2009, poisonings have been the leading cause of fatal injuries in
      the United States (US) and remain a continuing public health issue. Because of
      the varying definitions for what constitutes a poisoning case, there are
      inconsistencies in the annual number of cases reported among national health
      surveys. OBJECTIVES: The main objective of this study was to describe poisonings
      treated in Illinois hospitals by type of exposure, as well as to detail
      demographic characteristics, acute outcomes, and general cost estimates for those
      exposed to poisoning. We also compared a broad definition for poisoning used in
      our analysis with the definitions used by four national health surveys in order
      to assess the adequacy of various definitions in capturing poisonings for
      surveillance. MATERIAL AND METHODS: We conducted a comprehensive analysis of
      outpatients and inpatients treated in Illinois hospitals in 2010 using the
      Illinois hospital database. Age-adjusted incidence rates were calculated.
      RESULTS: In Illinois, 425,491 patients were treated in hospitals for poisoning in
      2010, of whom 222,339 were inpatients. The age-adjusted incidence rate was 3,189
      per 100,000 persons, with an average length of stay among inpatients of 5.5 days.
      The cumulative hospital charges were $7.9 billion. DISCUSSION AND CONCLUSION: The
      definitions used in national surveys miss 60-90% of poisoning cases. Poisoning is
      the leading cause of fatal injuries in the U.S., but as this study shows
      broadening the definition for poisoning may provide a more accurate
      representation of the direct and indirect effects of poisoning in the US.

PMID- 25871917
TI  - Nopaine no gain: recreational ethylphenidate toxicity.

PMID- 25871918
TI  - Cycloadditions in modern polymer chemistry.
AB  - Synthetic polymer chemistry has undergone two major developments in the last two
      decades. About 20 years ago, reversible-deactivation radical polymerization
      processes started to give access to a wide range of polymeric architectures made
      from an almost infinite reservoir of functional building blocks. A few years
      later, the concept of click chemistry revolutionized the way polymer chemists
      approached synthetic routes. Among the few reactions that could qualify as click,
      the copper-catalyzed azide-alkyne cycloaddition (CuAAC) initially stood out.
      Soon, many old and new reactions, including cycloadditions, would further enrich
      the synthetic macromolecular chemistry toolbox. Whether click or not,
      cycloadditions are in any case powerful tools for designing polymeric materials
      in a modular fashion, with a high level of functionality and, sometimes,
      responsiveness. Here, we wish to describe cycloaddition methodologies that have
      been reported in the last 10 years in the context of macromolecular engineering,
      with a focus on those developed in our laboratories. The overarching structure of
      this Account is based on the three most commonly encountered cycloaddition
      subclasses in organic and macromolecular chemistry: 1,3-dipolar cycloadditions,
      (hetero-)Diels-Alder cycloadditions ((H)DAC), and [2+2] cycloadditions. Our goal
      is to briefly describe the relevant reaction conditions, the advantages and
      disadvantages, and the realized polymer applications. Furthermore, the
      orthogonality of most of these reactions is highlighted because it has proven
      highly beneficial for generating unique, multifunctional polymers in a one-pot
      reaction. The overview on 1,3-dipolar cycloadditions is mostly centered on the
      application of CuAAC as the most travelled route, by far. Besides illustrating
      the capacity of CuAAC to generate complex polymeric architectures, alternative
      1,3-dipolar cycloadditions operating without the need for a catalyst are
      described. In the area of (H)DA cycloadditions, beyond the popular
      maleimide/furan couple, we present chemistries based on more reactive species,
      such as cyclopentadienyl or thiocarbonylthio moieties, particularly stressing the
      reversibility of these systems. In these two greater families, as well as in the
      last section on [2+2] cycloadditions, we highlight phototriggered chemistries as
      a powerful tool for spatially and temporally controlled materials synthesis.
      Clearly, cycloaddition chemistry already has and will continue to transform the
      field of polymer chemistry in the years to come. Applying this chemistry enables
      better control over polymer composition, the development of more complicated
      polymer architectures, the simplification of polymer library production, and the
      discovery of novel applications for all of these new polymers. 

PMID- 25871919
TI  - Discovery of a Previously Unrecognized Ribonuclease from Escherichia coli That
      Hydrolyzes 5'-Phosphorylated Fragments of RNA.
AB  - TrpH or YciV (locus tag b1266) from Escherichia coli is annotated as a protein of
      unknown function that belongs to the polymerase and histidinol phosphatase (PHP)
      family of proteins in the UniProt and NCBI databases. Enzymes from the PHP family
      have been shown to hydrolyze organophosphoesters using divalent metal ion
      cofactors at the active site. We found that TrpH is capable of hydrolyzing the 3'
      phosphate from 3',5'-bis-phosphonucleotides. The enzyme will also sequentially
      hydrolyze 5'-phosphomononucleotides from 5'-phosphorylated RNA and DNA
      oligonucleotides, with no specificity toward the identity of the nucleotide base.
      The enzyme will not hydrolyze RNA or DNA oligonucleotides that are
      unphosphorylated at the 5'-end of the substrate, but it makes no difference
      whether the 3'-end of the oligonucleotide is phosphorylated. These results are
      consistent with the sequential hydrolysis of 5'-phosphorylated mononucleotides
      from oligonucleotides in the 5' -> 3' direction. The catalytic efficiencies for
      hydrolysis of 3',5'-pAp, p(Ap)A, p(Ap)4A, and p(dAp)4dA were determined to be 1.8
      * 10(5), 9.0 * 10(4), 4.6 * 10(4), and 2.9 * 10(3) M(-1) s(-1), respectively.
      TrpH was found to be more efficient at hydrolyzing RNA oligonucleotides than DNA
      oligonucleotides. This enzyme can also hydrolyze annealed DNA duplexes, albeit at
      a catalytic efficiency approximately 10-fold lower than that of the corresponding
      single-stranded oligonucleotides. TrpH is the first enzyme from E. coli that has
      been found to possess 5' -> 3' exoribonuclease activity. We propose to name this
      enzyme RNase AM.

PMID- 25871920
TI  - Inference of cell-cell interactions from population density characteristics and
      cell trajectories on static and growing domains.
AB  - A key feature of cell migration is how cell movement is affected by cell-cell
      interactions. Furthermore, many cell migratory processes such as neural crest
      stem cell migration [Thomas and Erickson, 2008; McLennan et al., 2012] occur on
      growing domains or in the presence of a chemoattractant. Therefore, it is
      important to study interactions between migrating cells in the context of domain
      growth and directed motility. Here we compare discrete and continuum models
      describing the spatial and temporal evolution of a cell population for different
      types of cell-cell interactions on static and growing domains. We suggest that
      cell-cell interactions can be inferred from population density characteristics in
      the presence of motility bias, and these population density characteristics for
      different cell-cell interactions are conserved on both static and growing
      domains. We also study the expected displacement of a tagged cell, and show that
      different types of cell-cell interactions can give rise to cell trajectories with
      different characteristics. These characteristics are conserved in the presence of
      domain growth, however, they are diminished in the presence of motility bias. Our
      results are relevant for researchers who study the existence and role of cell
      cell interactions in biological systems, so far as we suggest that different
      types of cell-cell interactions could be identified from cell density and
      trajectory data. 

PMID- 25871921
TI  - How Formaldehyde Inhibits Hydrogen Evolution by [FeFe]-Hydrogenases:
      Determination by 13C ENDOR of Direct Fe-C Coordination and Order of Electron and
      Proton Transfers.
AB  - Formaldehyde (HCHO), a strong electrophile and a rapid and reversible inhibitor
      of hydrogen production by [FeFe]-hydrogenases, is used to identify the point in
      the catalytic cycle at which a highly reactive metal-hydrido species is formed.
      Investigations of the reaction of Chlamydomonas reinhardtii [FeFe]-hydrogenase
      with formaldehyde using pulsed-EPR techniques including electron-nuclear double
      resonance spectroscopy establish that formaldehyde binds close to the active
      site. Density functional theory calculations support an inhibited super-reduced
      state having a short Fe-(13)C bond in the 2Fe subsite. The adduct forms when HCHO
      is available to compete with H(+) transfer to a vacant, nucleophilic Fe site: had
      H(+) transfer already occurred, the reaction of HCHO with the Fe-hydrido species
      would lead to methanol, release of which is not detected. Instead, Fe-bound
      formaldehyde is a metal-hydrido mimic, a locked, inhibited form analogous to that
      in which two electrons and only one proton have transferred to the H-cluster. The
      results provide strong support for a mechanism in which the fastest pathway for
      H2 evolution involves two consecutive proton transfer steps to the H-cluster
      following transfer of a second electron to the active site. 

PMID- 25871922
TI  - High-resolution insights into the early stages of silver nucleation and growth.
AB  - Nucleation and growth of silver nanoparticles has already been investigated with
      various experimental and computational tools. However, owing to inherent problems
      associated with the analytical characterization of nucleation processes, there is
      a general lack of experimental data regarding the earliest precursors and
      smallest Ag(0) clusters. Here, we address this problem by the application of
      Synthetic Boundary Crystallization Ultracentrifugation, utilizing a
      multiwavelength detector for the first time, complemented by a specialized
      titration assay. These techniques shed new light on silver nanoparticle
      precursors existing in the pre-nucleation regime, and the initially nucleated
      ensemble of nanoclusters. For the first time, we present experimental data of UV
      Vis spectra for fractionated silver clusters. These allow for unsurpassed
      insights into the sequence of nucleation and early growth species as well as
      their optical properties. 

PMID- 25871923
TI  - Excessive range of statin dose in Western Australian primary care.
AB  - BACKGROUND: Statins are very effective in reducing coronary disease and ischaemic
      stroke but guidelines although evolving have not been clear on statin dose. AIM:
      To audit and review community statin prescribing. METHODS: A retrospective audit
      of the type and dose of statin dispensed was undertaken at five pharmacies in and
      around Perth, the capital city of Western Australia. Patients were de-identified.
      RESULTS: Statins made up 6.5% of all prescriptions. Statin dose when adjusted for
      different potency effectively varied 64-fold between patients. Rosuvastatin and
      atorvastatin accounted for 79% of prescriptions, at a mean dose of 10 times the
      effective dose 50. CONCLUSION: The extraordinarily wide variation in statin dose
      is at odds with the more consistent doses of other drugs used in the management
      of arterial disease. Unnecessarily high statin dosing increases side-effects and
      may not improve clinical outcomes appreciably. Rational prescribing of statins
      based on the pharmacodynamic evidence, with lower doses in most patients,
      combined with close attention to reduction of smoking, blood pressure and weight,
      is likely to reduce arterial disease most efficiently and safely.

PMID- 25871924
TI  - Phylogeny and evolutionary genetics of Frankia strains based on 16S rRNA and nifD
      K gene sequences.
AB  - 16S rRNA and nifD-nifK sequences were used to study the molecular phylogeny and
      evolutionary genetics of Frankia strains isolated from Hippophae salicifolia D.
      Don growing at different altitudes (ecologically classified as riverside and
      hillside isolates) of the Eastern Himalayan region of North Sikkim, India.
      Genetic information for the small subunit rRNA (16S rRNA) revealed that the
      riverside Frankia isolates markedly differed from the hillside isolates
      suggesting that the riverside isolates are genetically compact. Further, for
      enhanced resolutions, the partial sequence of nifD (3' end), nifK (5' end) and
      nifD-K IGS region have been investigated. The sequences obtained, failed to
      separate riverside isolates and hillside isolates, thus suggesting a possible
      role of genetic transfer events either from hillside to riverside or vice versa.
      The evolutionary genetic analyses using evogenomic extrapolations of gene
      sequence data obtained from 16S rRNA and nifD-K provided differing equations with
      the pace of evolution being more appropriately, intermediate. Values of
      recombination frequency (R), nucleotide diversity per site (Pi), and DNA
      divergence estimates supported the existence of an intermixed zone where spatial
      isolations occurred in sync with the temporal estimates. J. Basic Microbiol.
      2015, 54, 1-9. 

PMID- 25871925
TI  - A Dual-Catalysis Anion-Binding Approach to the Kinetic Resolution of Amines:
      Insights into the Mechanism via a Combined Experimental and Computational Study.
AB  - Racemic benzylic amines undergo kinetic resolution via benzoylation with benzoic
      anhydride in the presence of a dual catalyst system consisting of a readily
      available amide-thiourea catalyst and 4-dimethylaminopyridine (DMAP). An
      evaluation of various experimental parameters was performed in order to derive a
      more detailed understanding of what renders this process selective. The
      catalyst's aggregation behavior and anion-binding ability were evaluated in
      regard to their relevance for the catalytic process. Alternate scenarios, such as
      catalyst deprotonation or the in situ formation of a neutral chiral acylating
      reagent were ruled out. Detailed computational studies at the M06/6-31G(d,p)
      level of theory including solvent modeling utilizing a polarized continuum model
      provide additional insights into the nature of the ion pair and reveal a range of
      important secondary interactions that are responsible for efficient
      enantiodiscrimination. 

PMID- 25871926
TI  - Measurement of Proteasome Activity in Peripheral Blood Mononuclear Cells as an
      Indicator of Susceptibility to Bortezomib-Induced Severe Neurological Adverse
      Events in Patients with Multiple Myeloma.
AB  - AIMS: To explore the biomarker for predicting the occurrence of adverse events in
      myeloma patients treated by intravenous bortezomib, we measured proteasome
      activity in peripheral blood mononuclear cells. METHODS: Samples were obtained
      from 34 bortezomib-naive patients. Proteasome activity was measured at pre- and
      postchemotherapy phase by using a synthetic substrate. RESULTS: Bortezomib
      injection resulted in a dramatic decrease in proteasome activity, reaching 32.4
      +/- 18.79% (mean +/- SD) of the pretreatment level at 1 h, but it generally
      recovered at the end of the first course. In total, 6 patients manifested with
      severe bortezomib-induced peripheral neuropathy (sBIPN) in the second-third
      course. There was a nonsignificant trend for these patients to have lower levels
      of the relative proteasome activity at the end of the first course than those
      without sBIPN (median: 74.03 vs. 103.2%, p = 0.052). Moreover, in all of them,
      proteasome activity did not recover to the pretreatment level, whereas no
      patients with complete recovery manifested with sBIPN. Analysis with Fisher's
      exact test demonstrated that incomplete recovery of proteasome activity is a
      significant risk factor for sBIPN (p = 0.014). CONCLUSION: Patients with
      incomplete recovery of proteasome activity are at high risk for developing sBIPN,
      and the susceptible patients can be indicated by monitoring proteasome activity.

PMID- 25871927
TI  - Implementing a multifaceted intervention to decrease central line-associated
      bloodstream infections in SEHA (Abu Dhabi Health Services Company) intensive care
      units: the Abu Dhabi experience.
AB  - OBJECTIVE To determine whether implementation of a multifaceted intervention
      would significantly reduce the incidence of central line-associated bloodstream
      infections. DESIGN Prospective cohort collaborative. SETTING AND PARTICIPANTS
      Intensive care units of the Abu Dhabi Health Services Company hospitals in the
      Emirate of Abu Dhabi. INTERVENTIONS A bundled intervention consisting of 3
      components was implemented as part of the program. It consisted of a multifaceted
      approach that targeted clinician use of evidence-based infection prevention
      recommendations, tools that supported the identification of local barriers to
      these practices, and implementation ideas to help ensure patients received the
      practices. Comprehensive unit-based safety teams were created to improve safety
      culture and teamwork. Finally, the measurement and feedback of monthly infection
      rate data to safety teams, senior leaders, and staff in participating intensive
      care units was encouraged. The main outcome measure was the quarterly rate of
      central line-associated bloodstream infections. RESULTS Eighteen intensive care
      units from 7 hospitals in Abu Dhabi implemented the program and achieved an
      overall 38% reduction in their central line-associated bloodstream infection
      rate, adjusted at the hospital and unit level. The number of units with a
      quarterly central line-associated bloodstream infection rate of less than 1
      infection per 1,000 catheter-days increased by almost 40% between the baseline
      and postintervention periods. CONCLUSION A significant reduction in the global
      morbidity and mortality associated with central line-associated bloodstream
      infections is possible across intensive care units in disparate settings using a
      multifaceted intervention.

PMID- 25871928
TI  - Gene acquisition convergence between entomopoxviruses and baculoviruses.
AB  - Organisms from diverse phylogenetic origins can thrive within the same ecological
      niches. They might be induced to evolve convergent adaptations in response to a
      similar landscape of selective pressures. Their genomes should bear the signature
      of this process. The study of unrelated virus lineages infecting the same host
      panels guarantees a clear identification of phyletically independent convergent
      adaptation. Here, we investigate the evolutionary history of genes in the
      accessory genome shared by unrelated insect large dsDNA viruses: the
      entomopoxviruses (EPVs, Poxviridae) and the baculoviruses (BVs). EPVs and BVs
      have overlapping ecological niches and have independently evolved similar
      infection processes. They are, in theory, subjected to the same selective
      pressures from their host's immune responses. Their accessory genomes might,
      therefore, bear analogous genomic signatures of convergent adaption and could
      point out key genomic mechanisms of adaptation hitherto undetected in viruses. We
      uncovered 32 homologous, yet independent acquisitions of genes originating from
      insect hosts, different eukaryotes, bacteria and viruses. We showed different
      evolutionary levels of gene acquisition convergence in these viruses, underlining
      a continuous evolutionary process. We found both recent and ancient gene
      acquisitions possibly involved to the adaptation to both specific and distantly
      related hosts. Multidirectional and multipartite gene exchange networks appear to
      constantly drive exogenous gene assimilations, bringing key adaptive innovations
      and shaping the life histories of large DNA viruses. This evolutionary process
      might lead to genome level adaptive convergence. 

PMID- 25871929
TI  - Screening for Mutations in ABCC8 and KCNJ11 Genes in Saudi Persistent
      Hyperinsulinemic Hypoglycemia of Infancy (PHHI) Patients.
AB  - The autosomal recessive form of persistent hyperinsulinemic hypoglycemia of
      infancy (PHHI) is associated with mutations in either ABCC8 or KCNJ11 genes. In
      the present study, we describe the clinical features and results of genetic
      analysis of 13 Saudi Arabian patients with PHHI. Clinically, most patients
      presented with infantile seizures and/or developmental delay, with a subset of
      patients who were also found to have abnormal brain imaging and
      electrophysiological studies. Interestingly no coding pathogenic mutations were
      identified in these two genes by direct sequencing. However, two splice variants
      were identified in ABCC8 gene in two patients, and a large deletion of exons 1-22
      of the ABCC8 gene was identified in three patients. Our data shows that large
      deletions in ABCC8 gene are the common genetic mechanism in the Saudi population.

PMID- 25871930
TI  - Adolescents' experiences of using removable functional appliances.
AB  - OBJECTIVES: The aim of this qualitative study was to explore and describe
      adolescents' experiences of treatment with removable functional appliances.
      SETTING AND SAMPLE POPULATION: Public Dental Service, Gothenburg, Sweden.
      MATERIAL AND METHODS: Individual interviews focusing on adolescents' experiences
      of using a removable functional appliance were held with 21 adolescents (12 girls
      and nine boys). The mean age of the participants was 13.2 years (range 11-15, SD
      1.25) at the interview occasion. Interviews were transcribed verbatim and
      analysed according to a qualitative research approach, phenomenography. RESULTS:
      Outcomes of data analysis emerged in five categories with totally 12
      subcategories that describe the adolescents' various conceptions of the
      treatment. The adolescent's experiences of using removable functional appliance
      appeared to have a large variation, comprising of the individual approach,
      feelings and strategies, the dentist role and receiving external support.
      CONCLUSION: Participants developed their own strategies of measurement to see
      improvement. An active involvement of the adolescents' in the treatment seems to
      be needed, supported by the dentist at coming appointments, using overjet
      measurement as a tool for motivation. Furthermore, efforts should be made by
      clinicians to listen and understand adolescents' needs and requirement before the
      treatment start.

PMID- 25871931
TI  - Metatranscriptomes reveal functional variation in diatom communities from the
      Antarctic Peninsula.
AB  - Functional genomics of diatom-dominated communities from the Antarctic Peninsula
      was studied using comparative metatranscriptomics. Samples obtained from diatom
      rich communities in the Bransfield Strait, the western Weddell Sea and sea ice in
      the Bellingshausen Sea/Wilkins Ice Shelf yielded more than 500K pyrosequencing
      reads that were combined to produce a global metatranscriptome assembly. Multi
      gene phylogenies recovered three distinct communities, and diatom-assigned
      contigs further indicated little read-sharing between communities, validating an
      assembly-based annotation and analysis approach. Although functional analysis
      recovered a core of abundant shared annotations that were expressed across the
      three diatom communities, over 40% of annotations (but accounting for <10% of
      sequences) were community-specific. The two pelagic communities differed in their
      expression of N-metabolism and acquisition genes, which was almost absent in post
      bloom conditions in the Weddell Sea community, while enrichment of transporters
      for ammonia and urea in Bransfield Strait diatoms suggests a physiological stance
      towards acquisition of reduced N-sources. The depletion of carbohydrate and
      energy metabolism pathways in sea ice relative to pelagic communities, together
      with increased light energy dissipation (via LHCSR proteins), photorespiration,
      and NO3(-) uptake and utilization all pointed to irradiance stress and/or
      inorganic carbon limitation within sea ice. Ice-binding proteins and cold-shock
      transcription factors were also enriched in sea ice diatoms. Surprisingly, the
      abundance of gene transcripts for the translational machinery tracked decreasing
      environmental temperature across only a 4  degrees C range, possibly reflecting
      constraints on translational efficiency and protein production in cold
      environments. 

PMID- 25871934
TI  - Epidemiological and demographic HIV/AIDS projections: South Africa.
AB  - The Epidemic Projection Package (EPP) recently developed by the UNAIDS Reference
      Group on Estimates, Models and Projections and the Spectrum model program
      developed by the Futures Group were used to model the South African HIV epidemic,
      project future trends in HIV/AIDS and estimate the demographic impact of AIDS.
      The national HIV prevalence surveys among pregnant women from 1990-2001 and the
      first national, population-based HIV survey in 2002 served as the data sets used
      to calibrate the input HIV prevalence values for the model. The scenario created
      by the model showed that a dramatic rise in HIV prevalence during the 1990s has
      peaked in 2002 with 4.69 million infected people and it is projected that the
      epidemic in South Africa has now begun to level off. Adult (15-49 years)
      incidence rates have decreased substantially in the past five years since 1997
      (4.2%) and are expected to reach a level of 1.7% in 2003. The annual number of
      deaths due to AIDS is projected to peak with 487 320 AIDS deaths in the year
      2008. By 2020, the total population of South Africa is expected to be 23% smaller
      than it would be without AIDS, however, a negative population growth rate is not
      expected during the projection period. Life expectancy at birth is expected to
      hit a low of 45.6 years in the time period 2005-2010, which is 22 years less than
      it would have been in the absence of AIDS. Ten years from now over 2.5 million
      AIDS orphans are projected for South Africa. Models play an important role in
      estimating HIV variables that are difficult to measure. Projections of the future
      HIV/AIDS burden in South Africa underscore the importance of acting now to reduce
      the number of new infections and plan for medical and social care needs. 

PMID- 25871932
TI  - An active atmospheric methane sink in high Arctic mineral cryosols.
AB  - Methane (CH4) emission by carbon-rich cryosols at the high latitudes in Northern
      Hemisphere has been studied extensively. In contrast, data on the CH4 emission
      potential of carbon-poor cryosols is limited, despite their spatial predominance.
      This work employs CH4 flux measurements in the field and under laboratory
      conditions to show that the mineral cryosols at Axel Heiberg Island in the
      Canadian high Arctic consistently consume atmospheric CH4. Omics analyses present
      the first molecular evidence of active atmospheric CH4-oxidizing bacteria
      (atmMOB) in permafrost-affected cryosols, with the prevalent atmMOB genotype in
      our acidic mineral cryosols being closely related to Upland Soil Cluster alpha.
      The atmospheric (atm) CH4 uptake at the study site increases with ground
      temperature between 0  degrees C and 18  degrees C. Consequently, the atm CH4
      sink strength is predicted to increase by a factor of 5-30 as the Arctic warms by
      5-15  degrees C over a century. We demonstrate that acidic mineral cryosols are a
      previously unrecognized potential of CH4 sink that requires further investigation
      to determine its potential impact on larger scales. This study also calls
      attention to the poleward distribution of atmMOB, as well as to the potential
      influence of microbial atm CH4 oxidation, in the context of regional CH4 flux
      models and global warming. 

PMID- 25871933
TI  - Dominance of sulfur-fueled iron oxide reduction in low-sulfate freshwater
      sediments.
AB  - A central tenant in microbial biogeochemistry is that microbial metabolisms
      follow a predictable sequence of terminal electron acceptors based on the
      energetic yield for the reaction. It is thereby oftentimes assumed that microbial
      respiration of ferric iron outcompetes sulfate in all but high-sulfate systems,
      and thus sulfide has little influence on freshwater or terrestrial iron cycling.
      Observations of sulfate reduction in low-sulfate environments have been
      attributed to the presumed presence of highly crystalline iron oxides allowing
      sulfate reduction to be more energetically favored. Here we identified the iron
      reducing processes under low-sulfate conditions within columns containing
      freshwater sediments amended with structurally diverse iron oxides and
      fermentation products that fuel anaerobic respiration. We show that despite low
      sulfate concentrations and regardless of iron oxide substrate (ferrihydrite, Al
      ferrihydrite, goethite, hematite), sulfidization was a dominant pathway in iron
      reduction. This process was mediated by (re)cycling of sulfur upon reaction of
      sulfide and iron oxides to support continued sulfur-based respiration--a cryptic
      sulfur cycle involving generation and consumption of sulfur intermediates.
      Although canonical iron respiration was not observed in the sediments amended
      with the more crystalline iron oxides, iron respiration did become dominant in
      the presence of ferrihydrite once sulfate was consumed. Thus, despite more
      favorable energetics, ferrihydrite reduction did not precede sulfate reduction
      and instead an inverse redox zonation was observed. These findings indicate that
      sulfur (re)cycling is a dominant force in iron cycling even in low-sulfate
      systems and in a manner difficult to predict using the classical thermodynamic
      ladder.

PMID- 25871935
TI  - Behaviour and communication change in reducing HIV: is Uganda unique?
AB  - The clearest example of declines in HIV prevalence and changes in sexual
      behaviour comes from Uganda. Are there lessons to learn for other countries or is
      Uganda unique? In this paper, we assess the epidemiological and behavioural data
      on Uganda comparatively to other African countries and then analyse data from
      other populations where HIV has declined. In Uganda, HIV prevalence declined from
      21% to 9.8% from 1991-1998, there was a reduction in non-regular sexual partners
      by 65% and greater levels of communication about AIDS and people with AIDS
      through social networks, unlike the comparison countries. There is evidence of a
      basic population level response initiated at community level, to avoid risk,
      reduce risk behaviours and care for people with AIDS. The basic elements-a
      continuum of communication, behaviour change and care-were integrated at
      community level. They were also strongly supported by distinctive Ugandan
      policies from the 1980s. We identify a similar, early behaviour and communication
      response in other situations where HIV has declined: Thailand, Zambia and the US
      Gay community. In Thailand, visits to sex workers decreased by 55% and non
      regular partners declined from 28% to 15% (1990-1993): as important as the '100%
      condom use policy'. Similarly, in Zambia and Ethiopia risk behaviour has
      decreased and analysis of Sexually Transmitted Disease (STD) rates among Gay
      populations in the USA shows a decline from as early as 1985 in White Gay
      populations, with later declines in Hispanic and Black Gay populations. These
      responses preceded and exceeded HIV prevention. However, where they were built on
      by distinctive HIV policies, HIV prevention has been scaled and led to national
      level declines in HIV. It is not easy to transfer the lessons of these successes.
      They require real social and political capital in addition to financial capital.
      Nevertheless, similar characteristics are present in community responses in
      Africa, Asia and USA, and even in fragmented signs of HIV declines in other
      African cities. Only in a few situations has this behaviour and communication
      process been recognised, mobilised and built on by HIV prevention policy. Where
      this has occurred, HIV prevention success has been greater than biomedical
      approaches or methods introduced from outside. It represents a social vaccine for
      HIV from Africa, and is available now. 

PMID- 25871936
TI  - Investigating the interface between health system reform and HIV/AIDS in sub
      Saharan Africa: an approach for improving the fight against the epidemic.
AB  - During the period in which the HIV/AIDS epidemic has taken hold in sub-Saharan
      Africa, health system reforms have and continue to be introduced throughout the
      region. In spite of the multidisciplinary research undertaken, it can be
      questioned whether the relationships between processes of reform and some of the
      critical issues of HIV/AIDS response have been fully appreciated. This is
      particularly worrying since many countries in sub-Saharan Africa have already
      embarked on reform whilst concurrently and independently attempting to develop
      and manage effective responses to the overwhelming challenges posed by the
      HIV/AIDS epidemic. This paper explores the relationship between health system
      reform and HIV/AIDS, and argues that an interface approach is crucial for
      understanding the complexity of combating the epidemic whilst reforming health
      systems. The interface refers to the interacting processes between reform and the
      effects of the disease and attempts to respond to it. It includes the ways in
      which reforms, and such features as decentralisation and user fees, affect the
      capacity to fight HIV/AIDS, and conversely how the implications of the disease
      affect the performance of reformed health systems. Two sets of constraints in the
      interface are defined: internal and delivery constraints. The former are
      illustrated by deteriorating levels of human resources, poor integration of
      HIV/AIDS activities and problems faced by tiered health systems. The latter are
      illustrated by issues of access to relevant health services and rural-urban
      disparities. Issues in the interface need to be addressed by researchers and
      implementers in order to move forward in containing the epidemic. 

PMID- 25871937
TI  - Perceived social context of AIDS in a Black township in Cape Town.
AB  - AIDS is only one of several life threatening social problems facing people living
      in poverty. HIV/AIDS prevention messages and prevention programmes should be
      framed within the context of relevant social problems. The current study examined
      public perceptions of AIDS as a relative social problem and AIDS-related socio
      political beliefs among South African men and women living in a Black township of
      Cape Town. Participants (224 men and 276 women) completed surveys that assessed
      perceptions of HIV/AIDS relative to nine other social problems: lack of housing,
      transportation, poor sanitation, sufficient food, unemployment, discrimination,
      poor education, violence and crime. Participants also responded to six items
      assessing socio-political views of AIDS. Results showed that AIDS was perceived
      as a serious social problem in the township, but was perceived as less serious
      than crime and not different from violence and unemployment. Principal components
      factor analyses showed that AIDS was associated with multiple social problems and
      that AIDS was most closely associated with crime and violence, representing
      social problems that directly cause death. Although AIDS perceptions were similar
      to those expressed by the South African government, there was evidence for some
      mistrust about both what the government was doing and what it was saying about
      AIDS. HIV prevention messages in South Africa should be tailored to fit the
      perceived social context of AIDS. 

PMID- 25871938
TI  - Predicting the social consequences of orphanhood in South Africa.
AB  - This paper examines and questions the predictions found in the academic and
      policy literature of social breakdown in southern Africa in the wake of
      anticipated high rates of orphanhood caused by the AIDS epidemic. Analysis of the
      logic underlying these predictions reveals four causal relationships necessary to
      fulfil such dramatic and apocalyptic predictions: High AIDS mortality rates will
      produce high numbers of orphans. These orphans will become children who do not
      live in appropriate social environments to equip them for adult citizenship. Poor
      socialisation will mean that children orphaned by AIDS will not live within
      society's moral codes (becoming, for example, street children or juvenile
      delinquents). Large numbers of such 'asocial' or 'antisocial' children will
      precipitate a breakdown in the social fabric. Evidence for each of these steps in
      the argument is scrutinised using available data from southern Africa and other
      regions that have moved further through the epidemic's cycle. The paper finds
      strong evidence for the first step, although variable definitions of 'orphan'
      make it difficult to draw accurate comparisons over time and space. Evidence for
      the second step is found to be mixed in terms of outcomes of AIDS orphanhood for
      child well-being. Moreover the argument takes little account of the social and
      economic environments onto which AIDS is mapped, including the economic fragility
      of households and pervading socio-cultural patterns of child-rearing. Data to
      substantiate the third step are anecdotal at best and no research is able to
      demonstrate a link between the long term effects of AIDS orphanhood and rising
      rates of juvenile delinquency. Arguments made towards the fourth step are shown
      to be based heavily on notions of the 'correct' social and physical environments
      for children and on unsubstantiated fears of alternatives to these. There is no
      evidence from countries where numbers of AIDS orphans are already high to suggest
      that their presence is precipitating social breakdown. The paper argues-somewhat
      provocatively-that such apocalyptic predictions are unfounded and ill-considered.
      By misrepresenting the problems faced by children and their families, attention
      is distracted from the multiple layers of social, economic and psychological
      disadvantage that affect individual children, families and communities.
      Consequently, insufficient consideration is given to the multi-faceted supports
      necessary to assist children to cope with extremely difficult circumstances
      brought about over the long term by the HIV/AIDS epidemic. 

PMID- 25871939
TI  - Investigating attitudes towards caring for people with HIV/AIDS among hospital
      care workers in Ibadan, Nigeria: the role of self-efficacy.
AB  - Fear of HIV infection and its consequences may affect the willingness and
      capacity of health care workers to provide good quality care for people with
      HIV/AIDS (PWHAs). The study was founded on the proposition that self-efficacy may
      mediate the attitudinal disposition of health care workers related to provision
      of care to PWHAs. Two hundred and ten physicians (n = 103) and nurses (n = 107)
      sampled from the University College Hospital, Ibadan, Nigeria, responded (48%
      response rate) to a questionnaire which addressed self-efficacy relating to
      HIV/AIDS, knowledge about HIV/AIDS and treatment of and attitudes towards
      HIV/AIDS patients. Attitude questions included items on fear of HIV infection,
      futility in providing care for HIV patients, distress in caring for the patient
      who is likely to die and willingness to care for PWHAs. The major finding was a
      significant association between reported high selfefficacy and less fear of
      acquiring HIV, less futility in providing care for PWHAs and increased
      willingness to provide such care. More years of education was associated with
      higher willingness to care, less fear associated with care as well as lower
      perceived futility related to the care of PWHAs. Female gender was significantly
      related to the perception of futility related to the care of PWHAs. There was no
      significant relationship between self-efficacy and knowledge about HIV/AIDS. The
      findings have significant implications for hospital care for PWHAs and suggest
      that self-efficacy, rather than knowledge about HIV/AIDS may be important in
      mediating attitudes towards PWHAs and also in developing intervention programmes
      aimed at helping health care providers to reframe their attitudes. 

PMID- 25871940
TI  - Waging war: discourses of HIV/AIDS in South African media.
AB  - This paper explores a discourse of war against HIV/AIDS evident in the Daily
      Dispatch, a South African daily newspaper, from 1985 to 2000, and discusses the
      implications of this in terms of the way in which HIV/AIDS is constructed. The
      discursive framework of the war depends, fundamentally, on the personification of
      HIV/AIDS, in which agency is accorded to the virus, and which allows for its
      construction as the enemy. The war discourse positions different groups of
      subjects (the diseased body, the commanders, the experts, the ordinary citizens)
      in relations of power. The diseased body, which is the point of transmission, the
      polluter or infector, is cast as the 'Other', as a dark and threatening force.
      This takes on racialised overtones. The government takes on the role of
      commander, directing the war through policy and intervention strategies.
      Opposition to government is couched in a struggle discourse that dove-tails with
      the overall framework of war. Medical and scientific understandings pre-dominate
      in the investigative practices and expert commentary on the war, with alternative
      voices (such as those of people living with HIV/AIDS) being silenced. The
      ordinary citizen is incited to take on prevention and caring roles with a strong
      gendered overlay. 

PMID- 25871941
TI  - What's news: perspectives on HIV/AIDS advocacy in the South African print media.
AB  - This paper explores stakeholders' views regarding the question of whether
      HIV/AIDS coverage in the South African media should be the product of media
      advocacy and a proactive agenda for contributing to social change. Twenty-seven
      newspaper editors, journalists and other key stakeholders with a vested interest
      in HIV/AIDS coverage in the print media were interviewed during the course of
      2002. Two overriding issues were raised by informants for consideration. These
      were, firstly, the need to balance the journalistic objectives of (a) advocacy
      and (b) neutrality and, secondly, the need to balance the objectives of (a)
      advocacy and (b) news value and profitability. Findings suggest that reticence
      regarding the adoption of an explicit advocacy role regarding HIV/AIDS has much
      to do with the media's evolving relationship with the post-apartheid government
      and its controversial approach to HIV/AIDS. 

PMID- 25871942
TI  - Gradient Poly(styrene-co-polyglycidol) Grafts via Silicon Surface-Initiated AGET
      ATRP.
AB  - Gradient copolymer grafts of styrene and alpha-tert-butoxy-omega-vinylbenzyl
      poly(glycidol ethoxyethyl ether) (PGLet), a precursor of alpha-tert-butoxy-omega
      vinylbenzyl-polyglycidol macromonomer (PGL), were prepared on silicon wafers via
      a surface-initiated activator generated by electron transfer radical
      polymerization (AGET ATRP). Silicon plates with previously attached 2
      bromoisobutyrate served as a macroinitiator for the AGET ATRP (activator
      generated by electron transfer) of styrene and PGLet. The copolymers' gradient
      P(S-co-PPGL) of composition and thickness was obtained by a simple method where
      the plates were slowly removed from reaction mixture using a step motor. PGLet
      was added continuously (dropwise) into the reactor during withdrawal of the
      plates from solution in order to increase the relative concentration of PGLet in
      polymerization mixture. A range of strategies of making grafts was tested. The
      plates with copolymers grafts were analyzed by various techniques, like XPS,
      ellipsometry, and FTIR spectroscopy. The results indicate that the AGET ATRP
      process is dependent on the styrene/PGLet macromonomer ratio in the
      polymerization mixture. Under optimal conditions, the addition of PGLet during
      polymerization and subsequent deprotection of hydroxyl groups of PGLet permit to
      obtain plates with a novel copolymer layer with composition, thickness, and
      wettability gradient. Plates with chemical composition of copolymer grafts
      gradient served as versatile supports with controlled hydrophilic/hydrophobic
      area and were suitable for tailored deposition of particles. 

PMID- 25871943
TI  - Chronic portomesenteic venous thrombosis complicated by a high flow arteriovenous
      malformation presenting with gastrointestinal bleeding.
AB  - Portomesenteric venous thrombosis is a rare but potentially life-threatening
      condition. The presenting symptoms of chronic portomesenteric venous thrombosis
      are often non-specific but may present with variceal bleeding. We present the
      first reported case of chronic portomesenteric venous thrombosis causing a high
      flow arteriovenous malformation that resulted in extensive gastrointestinal
      bleeding. 

PMID- 25871944
TI  - Bioactive compounds in pindo palm (Butia capitata) juice and in pomace resulting
      of the extraction process.
AB  - BACKGROUND: Pindo palm (Butia capitata, Becc. 1916) is a tropical fruit native to
      South America and is relatively rich in bioactive compounds. It is often consumed
      as juice. The aim of this study was, first, to identify the degradation of these
      compounds by pasteurization and by cold storage (4  degrees C) of pindo palm
      juice. Physicochemical properties and concentrations of phenolic compounds,
      carotenoids and vitamin C have been evaluated on fresh and pasteurized juices.
      Moreover, another objective was to characterize the nutritional composition and
      the bioactive compounds of pindo palm pomace, the by-product of juice processing.
      RESULTS: The results demonstrated a degradation of carotenoids with
      pasteurization and a degradation of vitamin C with both pasteurization and cold
      storage of juices. Furthermore, the evaluation of pindo palm pomace showed that
      it is relatively rich in total phenols (20.06 g gallic acid equivalents kg(-1)
      dry matter) and in beta-carotene (0.22 g kg(-1) dry matter). CONCLUSION: Thus,
      from the nutrition viewpoint, it does not seem interesting to pasteurize juice.
      On the other hand, extraction of carotenoids and phenolic compounds from the
      pomace appears to be a relevant process.

PMID- 25871945
TI  - The behavioral economics of driving after drinking among college drinkers.
AB  - BACKGROUND: Driving after drinking (DAD) among college students is a significant
      public health concern, yet little is known about specific theoretical risk
      factors for DAD, beyond drinking level, among college student drinkers. This
      study had the following aims: (i) to examine the associations between elevated
      alcohol demand and DAD, (ii) to determine whether demand decreases in response to
      a hypothetical driving scenario, (iii) to determine whether drivers who report
      DAD in the past 3 months would show less of a reduction in demand in response to
      the hypothetical driving scenario, and (iv) to determine whether delayed reward
      discounting (DRD) is associated with DAD. METHOD: Participants were 419 college
      students who reported at least 1 day of past-month alcohol use. Participants
      completed 2 alcohol purchase tasks (APTs) that assessed hypothetical alcohol
      consumption across 17 drink prices with and without a driving scenario, a delay
      discounting task, and a series of questions regarding DAD. RESULTS: In logistic
      regression models that controlled for drinking level, demographics, and sensation
      seeking, participants reporting higher demand intensity (95% confidence interval
      [95% CI] [1.04, 2.34]), breakpoint (95% CI [1.23, 2.28]), Omax (95% CI [1.03,
      1.53]), and lower elasticity (95% CI [0.15, 1.02]) were more likely to report
      DAD. Additionally, in analyses of covariance, DAD(+) participants exhibited
      significantly less of a reduction in demand between the standard and the driving
      APT (intensity, p < 0.01, breakpoint, p = 0.05, and Omax , p < 0.01). A binary
      logistic regression model with identical covariates revealed that DRD is not
      associated with DAD. CONCLUSIONS: DAD is associated with elevated/inelastic
      demand and less sensitivity to a hypothetical driving scenario. Drinkers with
      elevated demand should be prioritized for DAD intervention efforts.

PMID- 25871946
TI  - Metal-organic framework composites: from fundamentals to applications.
AB  - Metal-organic frameworks (MOFs) are a class of crystallized porous polymeric
      materials consisting of metal ions or clusters linked together by organic
      bridging ligands. Due to their permanent porosity, rich surface chemistry and
      tuneable pore sizes, MOFs have emerged as one type of important porous solid and
      have attracted intensive interests in catalysis, gas adsorption, separation and
      storage over the past two decades. When compared with pure MOFs, the combination
      of MOFs with functional species or matrix materials not only shows enhanced
      properties, but also broadens the applications of MOFs in new fields, such as bio
      imaging, drug delivery and electrical catalysis, owing to the interactions of the
      functional species/matrix with the MOF structures. Although the synthesis,
      chemical modification and potential applications of MOFs have been reviewed
      previously, there is an increasing awareness on the synthesis and applications of
      their composites, which have rarely been reviewed. This review aims to fill this
      gap and discuss the fabrication, properties, and applications of MOF composites.
      The remaining challenges and future opportunities in this field, in terms of
      processing techniques, maximizing composite properties, and prospects for
      applications, have also been indicated. 

PMID- 25871947
TI  - The Relationship between Age-Related Macular Degeneration and Olfactory Function.
AB  - BACKGROUND: Olfactory dysfunction is a common symptom of many neurodegenerative
      diseases, and age-related macular degeneration (AMD) is a late-onset
      neurodegenerative disease. OBJECTIVE: Thus, the aim of this study was to
      investigate olfactory functions in patients with AMD. METHODS: A total of 69
      subjects with AMD and 69 age- and sex-matched healthy controls were enrolled.
      After a complete ophthalmic evaluation, the AMD patients were subclassified as
      early- and late-stage AMD. Psychophysical testing of olfactory function was
      performed using the validated Sniffin' Sticks test. RESULTS: This study was
      carried out in 138 subjects, with a mean age of 74.3 +/- 8.9 years (range 51-89).
      The current investigation showed the following two major findings: (1) patients
      with AMD had decreased olfactory abilities, especially in odor discrimination and
      odor identification, even at early stages compared to controls, whereas patients
      had decreased olfactory abilities in all subtasks of olfactory testings in
      advanced stages of AMD disease, and (2) as the visual acuity of AMD patients
      decreased, the olfactory abilities of these patients worsened. CONCLUSION: This
      study demonstrated that AMD had significant negative effects on all orthonasal
      olfactory tasks, particularly in advanced stages. Similar to other
      neurodegenerative diseases, odor discrimination and identification seemed to be
      more affected than odor detection threshold tasks.

PMID- 25871949
TI  - Aspirating during the intramuscular injection procedure: a systematic literature
      review.
AB  - AIMS AND OBJECTIVES: To review the available evidence on aspirating when
      administering intramuscular injections and suggest recommendations for practice.
      BACKGROUND: The process of aspiration has been ingrained in the intramuscular
      injection procedure, and whilst many policies no longer recommend this practice,
      it often continues to be taught and practiced. The result is a variation in this
      procedure not always consistent with an evidence-based approach. DESIGN: A
      systematic literature review. METHODS: A systematic approach to searching the
      literature was undertaken using identified academic databases from inception to
      May 2014. Citation searching identified additional data sources. Six studies met
      the search criteria. RESULTS: The majority of health professionals do not
      aspirate for the recommended 5-10 seconds. Administering an injection faster
      without aspiration is less painful than injecting slowly and aspirating. The main
      influences on the decision of whether or not to aspirate are based on what health
      professionals are taught and fear of injecting into a blood vessel. CONCLUSIONS:
      In the paediatric vaccination setting, the practice of aspirating during the
      administration of an intramuscular injection is unnecessary and there is no
      clinical reason to suggest that these principles may not be applied when using
      the deltoid, ventrogluteal and vastus lateralis sites in other settings. Owing to
      its proximity to the gluteal artery, aspiration when using the dorsogluteal site
      is recommended. Nurses must be supported in all settings, by clear guidance which
      rejects traditional practice and facilitates evidence-based practice. RELEVANCE
      TO CLINICAL PRACTICE: Educators need to ensure that their knowledge is up to date
      so that what they teach is based on evidence. This may be facilitated via regular
      educational updates. Further research and subsequent guidance are needed to
      support evidence-based practice in intramuscular injection techniques in all
      nursing settings.

PMID- 25871948
TI  - The human papillomavirus Test of Cure: A lesson on compliance with the NHMRC
      guidelines on screening to prevent cervical cancer.
AB  - BACKGROUND: In Australia, high-risk human papillomavirus (HR HPV) testing is
      recommended for follow-up of women treated for a high-grade squamous intra
      epithelial lesion (HSIL). The sensitivity of HR HPV testing is critical to
      identify women at risk of further high-grade cervical disease. In Australia, this
      management protocol is known as the 'Test of Cure' (ToC). AIM: To conduct a
      population-based study investigating practitioners' compliance with ToC.
      MATERIALS AND METHODS: Women treated for an HSIL between the five-year period 01
      Jan 2006 to 31 Dec 2010 were identified and followed up for at least a 27-month
      period. Proportions and relative odds were determined for women entering and
      completing the ToC management pathway within recommended time frames. RESULTS:
      There were 5,194 women identified as 'eligible' to enter the ToC management
      pathway. Of these, 1,916 (37%) were managed with annual Pap smears and never had
      a HR HPV test performed. There were 1,296 (25%) women who entered the ToC
      management pathway within recommended time frames, and a further 1,978 (38%)
      women entered outside of the recommended time frames. Overall, 961 women
      completed the ToC and were classified as 'cured' and were eligible to return to
      two-yearly Pap smears. Women's demographic information was significantly
      associated with ToC commencement, specifically, age and year of treatment, and
      Index of Relative Socioeconomic Disadvantage. CONCLUSION: Overall, a significant
      number of Australian women did not enter (~37%) and complete (~50%) the ToC
      management pathway. The challenge remains to advocate its use to practitioners to
      ensure women are returned to the population screening interval in a timely
      manner.

PMID- 25871950
TI  - Lipopolysaccharides-Induced Inflammatory Response in White Blood Cells Is
      Associated with Alterations in Senescence Mediators: Modulation by Metformin.
AB  - BACKGROUND: Sirtuin (SirT), a family of conserved histone deacetylases and
      transferases, has been proposed to function in inflammatory, cancer, and
      metabolic diseases. However, it is unclear how SirT modulates these processes. In
      this study, the effect of metformin on senescence and antisenescence mediators
      (SirT1-7, p53, and p16(INK4a)) mRNA expression in white blood cells (WBCs)
      following lipopolysaccharides (LPS)-induced inflammation in mice was examined.
      MATERIAL AND METHODS: C57BL/6 mice were treated with metformin in their drinking
      water (2 mg/mL) for 1 week followed by intraperitoneal injection of LPS from
      Escherichia coli serotype 0111:B4 at 2 mg/kg. Blood was collected at the basal
      level and 1, 2, and 3 hr after LPS injection. SirT1-7, p53, and p16(INK4a) mRNA
      expression in WBCs was measured by real-time quantitative polymerase chain
      reaction (RT-qPCR). RESULTS: SirT7 at 2 hr, SirT1 at 3 hr, and p16(INK4a) at 1 hr
      were inhibited significantly in WBCs following LPS injection. There were no
      significant changes in other SirT nor p53 mRNA expression in WBCs after LPS
      injection. Metformin inhibited SirT2 expression in WBCs significantly (P<0.05)
      and did not induce any significant changes in other SirT forms and p53, whereas
      it induced p16(INK4a) mRNA expression in WBCs (P<0.05) at the basal levels.
      Additionally, metformin treatment significantly inhibited SirT7, SirT1, and
      p16(INK4a) mRNA expression in WBCs at 1, 2, and 3 hr, whereas p53 was inhibited
      significantly at 2 hr after LPS injection. CONCLUSIONS: SirT7 and SirT1 are
      stress responsive proteins that may mediate inflammation. The data suggest that
      metformin may exert its potential antisenescence and anti-inflammatory effects by
      targeting SirT7 and SirT1 pathways. SirT7 inhibition may allow the healing
      process and prevention of tissue damage by enabling cells to survive through
      inhibition of cytokines and inflammatory mediators under severe stress
      conditions.

PMID- 25871951
TI  - Safety analysis of zolpidem in elderly subjects 80 years of age or older: adverse
      event monitoring in Japanese subjects.
AB  - OBJECTIVES: Prescriptions of non-benzodiazepine sedative hypnotics, e.g.
      zolpidem, for insomnia in elderly subjects 80 years of age or older have markedly
      increased in the USA. However, a meta-analysis of the risks and benefits of
      hypnotics in older people reported the benefits associated with hypnotics use are
      outweighed by the risks. This study aimed to investigate the safety of zolpidem
      administration in extremely old elderly. METHODS: The prevalence of adverse
      reactions to zolpidem was investigated in a subpopulation of participants in the
      Drug Event Monitoring project of the Japan Pharmaceutical Association. A total of
      1011 (316 males and 695 females) zolpidem users, including 261 (25.8%) subjects
      80 years of age or older without cognitive or mental complications, were eligible
      for the analysis. RESULTS: The elderly and female patients were prescribed
      significantly lower doses of zolpidem than their counterparts. Adverse symptoms
      after the last prescription were reported by 60 (5.9%) subjects. The most common
      symptoms were impaired balance and/or falls (1.8%) and morning drowsiness (1.3%).
      The multiple logistic regression analyses showed that subjects 80 years of age or
      older were at lower risk of adverse symptoms (odds ratio 0.39, 95% confidence
      intervals: 0.17-0.88). CONCLUSION: Our findings in a real-world clinical setting
      suggest that low-dose zolpidem can be safely prescribed to subjects 80 years of
      age or older without cognitive or mental complications.

PMID- 25871952
TI  - Isoindigo-based polymer field-effect transistors: effects of selenophene
      substitution on high charge carrier mobility.
AB  - We show that selenophene-substitution can be an efficient synthetic strategy
      toward high charge carrier mobility of isoindigo (IID)-based copolymers when
      their side chains are optimized. A high mobility of 5.8 cm(2) V(-1) s(-1) is
      demonstrated by a strategically designed IID-based polymer, with both side-chain
      adjustment and selenophene-substitution. 

PMID- 25871953
TI  - Lateral Growth of Composition Graded Atomic Layer MoS(2(1-x))Se(2x) Nanosheets.
AB  - Band gap engineering of transition-metal dichalcogenides is an important task for
      their applications in photonics, optoelectronics, and nanoelectronics. We report
      for the first time the continuous lateral growth of composition graded bilayer
      MoS(2(1-x))Se(2x) alloys along single triangular nanosheets by an improved
      chemical vapor deposition approach. From the center to the edge of the nanosheet,
      the composition can be gradually tuned from x = 0 (pure MoS2) to x = 0.68,
      leading to the corresponding bandgap being continuously modulated from 1.82 eV
      (680 nm) to 1.64 eV (755 nm). Local photoluminescence scanning from the center to
      the edge gives single band edge emission peaks, indicating high crystalline
      quality for the achieved alloy nanosheets, which was further demonstrated by the
      microstructure characterizations. These novel 2D structures offer an interesting
      system for probing the physical properties of layered materials and exploring new
      applications in functional nanoelectronic and optoelectronic devices.

PMID- 25871954
TI  - Adrenal adenomas, subclinical hypercortisolism, and cardiovascular outcomes.
AB  - PURPOSE OF REVIEW: Recent evidence has highlighted the link between
      cardiovascular outcomes and incidentally discovered adrenal masses. The purpose
      of this review is to summarize the most recent findings on the cardiovascular
      profile of patients with nonfunctional adrenal adenomas. RECENT FINDINGS:
      Nonsecreting adrenal tumors, defined mostly by cortisol levels after
      dexamethasone suppression test below 1.8 MUg/dl, are associated with impairment
      of markers of subclinical atherosclerosis such as intima-media thickness and flow
      mediated vasodilation. The presence of impaired indices of insulin resistance
      could represent an additional factor that contributes to the worsening of the
      cardiovascular profile of those patients. No evidence of increased cardiovascular
      outcomes was found in this group of patients. On the contrary, according to the
      findings of recent long-term retrospective studies, patients with subclinical
      hypercortisolism have an increased incidence of cardiovascular outcomes and
      related mortality with respect to nonsecreting adrenal masses and to the general
      population. SUMMARY: An impaired cardiovascular profile is a common finding in
      patients with apparently nonfunctional adrenal masses. However, the incidence of
      cardiovascular outcomes and related mortality seems to be increased only in
      patients with mild cortisol hypersecretion.

PMID- 25871956
TI  - Androgens and obesity in male adolescents.
AB  - PURPOSE OF REVIEW: Data on sex steroid levels and pubertal development in obese
      adolescent boys are scarce and contrasting. The present review summarizes the
      most recent results obtained with improved methodology to measure low sex steroid
      levels in children. RECENT FINDINGS: Obese pubertal boys have lower serum sex
      hormone-binding globulin and consequently lower total testosterone levels
      compared to normal-weight peers. However, during pubertal development, free
      testosterone levels in obese adolescents are not different from controls,
      indicating preserved androgen exposure as is additionally suggested by similar
      clinical genital staging (Tanner), serum gonadotropins levels, and serum prostate
      specific antigen concentrations compared to nonobese adolescents. In pre and
      early puberty, total testosterone levels is not decreased, notwithstanding low
      sex hormone-binding globulin, and free testosterone is slightly increased in
      obese boys. This may result from increased adrenal activity as revealed by
      elevated serum androstenedione and dehydroepiandrosterone sulfate. In obese
      adolescent boys, increased aromatization of testosterone to estradiol tends to
      accelerate skeletal maturation. SUMMARY: In obese adolescent boys, free
      testosterone is a better index than total testosterone levels of androgen status,
      which is not different from nonobese controls. Increased aromatization of
      testosterone to estradiol underlies the dissociation between normal clinical
      sexual maturation and advanced skeletal maturation in the obese adolescent.

PMID- 25871955
TI  - Cortisol dysregulation in obesity-related metabolic disorders.
AB  - PURPOSE OF REVIEW: The present review highlights recent investigations in the
      prior 18 months focusing on the role of dysregulated cortisol physiology in
      obesity as a potential modifiable mechanism in the pathogenesis of obesity
      related cardiometabolic disorders. RECENT FINDINGS: Given the clinical
      resemblance of obesity-related metabolic disorders with the Cushing's syndrome,
      new studies have investigated the intracellular regulation and metabolism of
      cortisol, new measurements of cortisol in scalp hair as a tool for long-term
      exposure to cortisol, and the cortisol-mineralocorticoid receptor pathway. Thus,
      current and future pharmacological interventions in obesity may include specific
      inhibition of steroidogenic and regulatory enzymes as well as antagonists of the
      mineralocorticoid and glucocorticoid receptors. SUMMARY: The understanding of how
      adrenal function is challenged by the interplay of our genetic and environmental
      milieu has highlighted the importance of inappropriate cortisol regulation in
      cardiometabolic disorders. Increased adipose tissue in obesity is associated with
      hypothalamic-pituitary-adrenal axis overactivation, increased cortisol production
      at the local tissue level, and probably higher mineralocorticoid receptor
      activation in certain tissues.

PMID- 25871957
TI  - Safety concerns regarding 5alpha reductase inhibitors for the treatment of
      androgenetic alopecia.
AB  - PURPOSE OF REVIEW: To examine the clinical and basic studies regarding persistent
      adverse effects associated with 5alpha reductase inhibitor treatment for
      androgenetic alopecia. RECENT FINDINGS: Recent postmarketing reports and a US
      Food and Drug Administration analysis have documented uncommon persistent sexual
      and nonsexual side-effects in a subset of younger men who have taken finasteride
      1 mg for androgenic alopecia. While the mechanisms of the sexual side-effects in
      humans is incompletely understood, one study found lower cerebrospinal fluid
      concentrations of dihydrotestosterone, progesterone, dihydroprogesterone and
      allopregnanolone, and higher levels of testosterone, 5alpha-androstane
      3alpha,17beta-diol and pregnenolone. Another study found up-regulation of the
      androgen receptor in the human foreskin with a mean of 5 years after finasteride
      discontinuation. Studies of erectile dysfunction in finasteride-treated rats
      showed fewer autophagosomes in smooth muscle on transmission electron microscopy,
      increased apoptosis, decreased smooth muscle, increased collagen deposition and
      decreased endothelial nitric oxide synthase. Finally, 5alpha reductase inhibitors
      have also been found to alter semen parameters in healthy men. SUMMARY: Multiple
      animal studies provide a biological basis for many of the persistent effects seen
      in humans such as erectile dysfunction, depression and decreased alcohol
      consumption. Prescribers of 5alpha reductase inhibitors should discuss the
      potential risks with their patients seeking treatment for androgenetic alopecia.

PMID- 25871958
TI  - Progress and prospects for fertility preservation in prepubertal boys with
      cancer.
AB  - PURPOSE OF REVIEW: In the past few years, options for fertility preservation in
      prepubescent boys have enlarged tremendously. RECENT FINDINGS: After a long
      period of studies on spermatogonial stem cell (SSC) transplantation in mice,
      recently successful use of rhesus monkey SSCs for autologous and allogeneic
      transplantation was demonstrated. Furthermore, newer protocols on transplantation
      of SSCs back into the testes and on how to mimic the niche environment have been
      described. Very importantly, a new multiparametric sorting strategy to eliminate
      cancer contamination from human testis cell suspension has been clarified.
      SUMMARY: While awaiting for more data on safety issues, retrieval and
      cryopreservation of testicular tissue prior to cancer therapy should be offered,
      within an experimental context, to prepubertal boys with cancer who are at high
      risk of fertility loss.

PMID- 25871959
TI  - Testicular function and fertility preservation after treatment for haematological
      cancer.
AB  - PURPOSE OF REVIEW: Treatment for high-risk or relapsed haematological malignancy
      with haematopoietic stem cell transplantation is known to cause infertility.
      Today, there are no established options for fertility preservation in pre
      pubertal boys. This review aims to describe how therapy for haematological
      malignancy in childhood affects male fertility, and to summarize recent
      developments for fertility preservation in these patients. RECENT FINDINGS:
      Eventual recovery of spermatogenesis is probable after chemotherapy-based
      conditioning for haematopoietic stem cell transplantation. However, conditioning
      with total body irradiation is associated with a very high risk of permanent
      infertility. For high-risk patients, auto-transplantation of cryopreserved
      testicular tissue or cells might represent an approach for fertility
      preservation; however, contamination of testis tissue with malignant cells may
      prevent their subsequent reintroduction into patients. Recent progress using in
      vitro differentiation of germ cells combined with assisted reproductive
      techniques may, in the future, represent a suitable alternative to
      retransplantation. SUMMARY: Particular care must be taken when assessing
      infertility risk in patients with haematological malignancy as reclassification
      to high risk may significantly increase the likelihood of treatment-related
      gonadotoxicity. Importantly, development of fertility preservation strategies in
      such high-risk patients must also take into account specific risks for
      haematological cancers including cancer cell contamination.

PMID- 25871960
TI  - Screening for Klinefelter syndrome.
AB  - PURPOSE OF REVIEW: To examine recently published evidence that may inform the
      need for population screening of Klinefelter syndrome; by far the most common
      chromosomal disorder in males, which most often escapes diagnosis throughout the
      lifespan. RECENT FINDINGS: Research regarding the prevalence and characteristics
      of developmental and learning difficulties in Klinefelter syndrome emphasize the
      importance of early intervention with likely subsequent psychosocial and other
      health benefits. Testosterone treatment will always need to be individualized,
      but there is growing evidence for the benefits of intervention from the time of
      puberty, and possibly in early childhood. Discussion of fertility options is now
      essential given the advent of surgical sperm retrieval and intracytoplasmic sperm
      injection. SUMMARY: Despite increasing knowledge of the natural history of the
      Klinefelter syndrome spectrum, beneficial interventions and when they should
      occur, most opportunities are missed due to nondiagnosis. Population screening is
      arguably the only way of ensuring timely detection of individuals with
      Klinefelter syndrome. The technologies and structures for such a program already
      exist. This field now requires a pilot program to further define the risks,
      benefits and psychosocial and ethical dimensions of screening.

PMID- 25871961
TI  - Subclinical hypercortisolism in adrenal incidentaloma.
AB  - PURPOSE OF REVIEW: The article aims to update the reader on current developments
      in the area of adrenal incidentaloma complicated by subclinical hypercortisolism.
      We will discuss different diagnostic strategies and complications associated with
      this disease, and address the conflicting opinions related to the treatment of
      these patients. RECENT FINDINGS: Depending on diagnostic criteria used, between
      30 and 50% of patients with adrenocortical incidentaloma have biochemical
      hypercortisolism, but lack classical external features of Cushing's syndrome. The
      challenge facing the clinician is that in the sixth and seventh decade of life
      hypertension, diabetes, osteoporosis and obesity are common and establishing
      whether these are directly related to the low-grade excess cortisol secretion in
      a given individual is not straightforward. Nevertheless, this subclinical
      hypercortisolism has been found to be associated with multiple cardiovascular
      risk factors, an increased predisposition to cardiovascular events and a higher
      mortality rate. The dilemma is that it is not established whether surgical
      excision of the adrenal adenoma in a given individual will improve these
      complications, and data demonstrate that surgical studies are conflicting.
      SUMMARY: Subclinical hypercortisolism is associated with multiple complications
      and definite guidelines for diagnosis are necessary. Prospective, randomized
      controlled studies are needed to ascertain whether medical or surgical
      interventions are justified, and in which patients.

PMID- 25871962
TI  - Next-generation sequencing for the diagnosis of hereditary pheochromocytoma and
      paraganglioma syndromes.
AB  - PURPOSE OF REVIEW: About 40% of the neuroendocrine tumors pheochromocytomas and
      paragangliomas (PPGLs) are caused by an inherited mutation. Diagnostic genetic
      screening is recommended for patients and their families. However, the number of
      susceptibility genes involved is high and continues to grow, making conventional
      sequencing costly and burdensome. Next-generation sequencing (NGS) enables
      accurate, thorough, and cost-effective identification of inherited mutations.
      Here we review recent successes, limitations, and the future of NGS for diagnosis
      of pheochromocytoma and paraganglioma syndromes. RECENT FINDINGS: NGS-based
      screen of genetic disorders in the clinical setting shows improved diagnostic
      rates over conventional tests. Both broad, whole-exome sequencing, and targeted
      NGS approaches have been tested for screening of PPGLs, with accurate mutation
      detection, higher speed, and reduced costs compared with current assays.
      Flexibility to expand the targeted gene set is immediate in whole-exome
      sequencing, and adjustable in targeted NGS, but both methods have limitations.
      SUMMARY: The high degree of genetic heterogeneity and heritability of PPGLs make
      NGS an ideal medium for their diagnostic screening. However, improved detection
      of large genomic defects and underrepresented gene areas are needed before NGS
      can fully realize its potential as the premier option for routine genetic testing
      of these syndromes.

PMID- 25871963
TI  - Protein kinase A defects and cortisol-producing adrenal tumors.
AB  - PURPOSE OF REVIEW: Cushing syndrome caused by cortisol-producing adrenal adenomas
      is a rare condition, associated with high morbidity due to weight gain, diabetes
      mellitus, osteoporosis, hypertension, muscle weakness, mood disturbance and
      others. The first gene to be identified as causative of Cushing syndrome was
      PRKAR1A. We present an update on protein kinase A (PKA) defects and Cushing
      syndrome. RECENT FINDINGS: The cyclic AMP-dependent PKA catalytic subunit alpha
      (PRKACA) hotspot point mutation (c.617A > C [p.Leu206Arg]), leading to an
      increase of basal PKA activity, and formation of cortisol-producing adenoma has
      been frequently shown to cause the most common form of adrenocorticotropic
      hormone-independent Cushing syndrome. SUMMARY: Somatic PRKACA mutations have been
      found in up to 50% of patients with adrenal adenomas. Germline PRKACA
      amplification was also seen in bilateral adrenal hyperplasias. PRKACA activation
      was associated with higher cortisol levels, smaller tumor size and overt Cushing
      syndrome. This breakthrough is expected to improve our understanding of how PKA
      defects lead to Cushing syndrome and may spearhead the development of new,
      molecularly designed therapies.

PMID- 25871964
TI  - Nuclear imaging in the diagnosis of primary aldosteronism.
AB  - PURPOSE OF REVIEW: Primary aldosteronism is increasingly recognized as a common
      secondary cause of hypertension. Successful demonstration of a unilateral cause
      (e.g. a classical 'Conn's adenoma') offers the potential for curative
      adrenalectomy. Adrenal vein sampling (AVS), in conjunction with cross-sectional
      imaging, remains the 'gold standard' for distinguishing unilateral and bilateral
      disease, but is technically demanding and frequently unsuccessful or
      inconclusive. As such, alternative strategies for lateralization, including
      nuclear medicine techniques, are being developed and brought into clinical
      practice. RECENT FINDINGS: Metomidate, a potent ligand of CYP11B1 and CYP11B2,
      can be C11H3-labelled as a PET tracer and has been shown to offer a rapid
      noninvasive alternative to AVS for localizing unilateral aldosterone-producing
      adenomas. SUMMARY: Increasing experience with 11C-metomidate PET-CT supports its
      use as an adjunct to AVS when this has failed, is ambiguous, or cannot be
      undertaken.

PMID- 25871965
TI  - Close Positive Correlation between the Lymphocyte Response to Hen Egg White and
      House Dust Mites in Infants with Atopic Dermatitis.
AB  - BACKGROUND: It was recently hypothesized that food allergens sensitize infants
      with atopic dermatitis (AD) via the skin. If this is the case, an intimate
      positive correlation should be observed between immune responses to both food and
      indoor allergens. METHODS: One hundred and seven infants with AD and 32 controls
      were enrolled. The proliferation of lymphocytes stimulated with hen egg white
      (EW) or house dust mite (HDM) allergens was measured by means of an allergen
      specific lymphocyte stimulation test (ALST). Cytokine production was measured in
      13 patients and 4 controls. RESULTS: ALST responses for EW (EW-ALST) were
      significantly higher in AD infants than in control subjects (stimulation index:
      7.98 vs. 2.54, p < 0.0001). HDM-ALST responses were also significantly higher in
      AD infants than in controls (stimulation index: 5.09 vs. 1.44, p < 0.0001). A
      significant positive correlation was seen between HDM-ALST and EW-ALST responses
      in AD infants aged 5-6 months (rs = 0.77, p < 0.000001). Serum levels of EW
      specific IgE (EW-IgE) were significantly correlated with both EW-ALST (rs = 0.43,
      p < 0.05) and HDM-ALST levels (rs = 0.47, p < 0.05) in AD patients aged 3-4
      months. Serum EW-IgE levels in AD infants were significantly correlated with the
      ratio of IL-4/IFN-gamma production from lymphocytes stimulated with EW (rs =
      0.62, p < 0.01) and with HDM (rs = 0.67, p < 0.005). CONCLUSIONS: This study
      describes the close positive correlation between EW- and HDM-specific immune
      responses in infants with AD. These results may support the hypothesis that both
      food and indoor allergens concurrently sensitize infants via the skin.

PMID- 25871967
TI  - MicroRNA-449a inhibits proliferation and induces apoptosis by directly repressing
      E2F3 in gastric cancer.
AB  - BACKGROUND: MicroRNA-449a is a tumor suppressor that is down-regulated in
      multiple tumors types. However, the role of miR-449a in gastric cancer (GC)
      remains largely unknown. METHODS: MiR-449a expression was up-regulated using miR
      449a mimics, and the role of miR-449a in GC was assessed using cell viability and
      apoptosis assays. miR-449a target genes were confirmed using luciferase activity,
      RT-PCR and western blot assays. RESULTS: miR-449a was downregulated in gastric
      cancer cell lines and gastric cancer tissues. Restoration of miR-449a expression
      inhibited gastric cancer cell proliferation and colony formation. Significant
      G0/G1 arrest was observed in gastric cancer cells transfected with miR-449a
      mimics. Furthermore, combination therapy with miR-449a with cisplatin displayed
      greater anti-tumor effects than treatment with cisplatin alone. We also
      identified E2F3 (E2F transcription factor 3), an important transcription factor
      involved in the proliferation and metastasis of tumor cells, as a direct target
      gene of miR-449a. Furthermore, silencing E2F3 elicits similar a repressive effect
      as overexpression of miR-449a in gastric cancer cells, and E2F3 overexpression
      rescued the repressing effects of miR-449a mimics. CONCLUSIONS: This study
      indicates that the miR-449a/E2F3 axis plays an important role in proliferation
      and apoptosis in gastric cancer. Therefore, miR-449a represents a novel target
      for gastric cancer therapy.

PMID- 25871966
TI  - Procoagulant microparticles in dogs with immune-mediated hemolytic anemia.
AB  - BACKGROUND: Studies of some human prothrombotic diseases suggest that
      phosphatidylserine-positive (PS+) and tissue factor-positive (TF+) microparticles
      (MPs) might play a role in the pathogenesis of thrombosis or serve as biomarkers
      of thrombotic risk. HYPOTHESIS/OBJECTIVES: To determine if circulating levels of
      PS+MP and procoagulant activity (PCA) associated with PS+MPs and TF+ MPs are
      increased in dogs with IMHA. ANIMALS: Fifteen dogs with primary or secondary IMHA
      and 17 clinically healthy dogs. METHODS: Prospective case-controlled
      observational study. Circulating PS+MPs were measured by flow cytometry. PCA
      associated with PS+MPs and TF+MPs was measured by thrombin and Factor Xa
      generating assays, respectively. RESULTS: Circulating numbers of PS+MPs were not
      significantly higher in dogs with IMHA [control median 251,000/MUL (36,992
      1,141,250/MUL); IMHA median 361,990/MUL (21,766-47,650,600/MUL) P = .30].
      However, PS+MP PCA [control median 2.2 (0.0-16.8) nM PS eq; IMHA median 8.596, (0
      49.33 nM PS eq) P = .01] and TF+MP PCA [control median 0.0, (0.0-0.0 pg/mL); IMHA
      median 0.0; (0-22.34 pg/mL], P = .04) were increased. Intravascular hemolysis,
      which we showed might increase PS+ and TF+MP PCA, was evident in 3 of 5 dogs with
      PS+MP PCA and 2 of 4 dogs with TF+MP PCA higher than controls. Underlying disease
      in addition to IMHA was detected in 1 of 5 dogs with PS+PCA and 3 of 4 dogs with
      TF+MP PCA higher than controls. CONCLUSIONS AND CLINICAL IMPORTANCE: TF+ and
      PS+MP PCA is increased in some dogs with IMHA. Further studies that determine if
      measuring TF+ and PS+ MP PCA can help identify dogs at risk for thrombosis are
      warranted.

PMID- 25871968
TI  - Comment on "enhanced elimination of perfluorooctanesulfonic Acid by menstruating
      women: evidence from population-based pharmacokinetic modeling".

PMID- 25871969
TI  - Experimental studies on the recovery processes from severe facial palsy and the
      development of its sequelae.
AB  - OBJECTIVE: To experimentally elucidate the pathogenesis of inappropriate co
      contraction of facially innervated muscles after severe facial palsy. METHODS:
      Twenty-two guinea pigs with severe facial palsy induced by the interruption of
      the petrosal artery were used to follow up behavioral facial movement, including
      the degree of facial palsy and abnormal hyperkinetic facial movement of
      synkinesis and mass contracture. At the end of the follow-up, the evoked facial
      compound muscle action potential (evoked FCMP) and antidromically evoked facial
      nerve response (AFNR) were examined in a few typical cases with complete recovery
      and with incomplete recovery accompanied by synkinesis. After the follow-up, all
      animals were sacrificed for morphological studies, which consisted of a light
      microscopic study (by Luxol fast blue and hematoxylin and eosin staining or
      toluidine blue staining) and/or an electron-microscopic study. RESULTS: The
      initial sign of recovery was mass contracture or spasm. This condition continued
      for 2 weeks or more. As voluntary facial movement recovered, the mass contracture
      became unnoticeable. It could not be distinguished when the so-called synkinesis
      developed. Synkinesis usually developed during the recovery process from severe
      to moderate palsy, and synkinesis persisted or progressed once it appeared.
      Histologically, unmyelinated fibers were intermingled with myelinated fibers in
      an early stage of recovery with mass contracture. In the late stage with the
      development of synkinesis, however, such an intermingling of unmyelinated and
      myelinated axons was not observed. In this stage, axons became well myelinated,
      but they were irregular in shape in cases with synkinesis. Especially, axons
      irregularly ran at the level of the G1 (at the region of the second genu)
      segment, and bifurcated axons were sporadically found. The axon count had a
      tendency to increase toward the periphery. AFNR was not detected, although evoked
      FCMP could be clearly detected in cases with synkinesis. CONCLUSION: Misguidance
      of regenerated axons is an important cause of facial synkinesis in the ischemia
      induced facial palsy model. Ephaptic transmission between unmyelinated and
      myelinated axons is also likely to be responsible for mass contracture manifested
      in the early stage of the recovery process.

PMID- 25871970
TI  - Sphingosylphosphorylcholine protects cardiomyocytes against ischemic apoptosis
      via lipid raft/PTEN/Akt1/mTOR mediated autophagy.
AB  - Autophagy, evoked by diverse stresses including myocardial ischemia/reperfusion
      (I/R), profoundly affects the development of heart failure. However, the specific
      molecular basis of autophagy remains to be elucidated. Here we report that
      sphingosylphosphorylcholine (SPC), a bioactive sphingolipid, significantly
      suppressed apoptosis and induced autophagy in cardiomyocytes. Blocking this SPC
      evoked autophagy by 3-methyladenine (3MA)-sensitized cardiomyocytes to serum
      deprivation-induced apoptosis. Subsequent studies revealed that SPC downregulated
      the phosphorylation of p70S6K and 4EBP1 (two substrates of mTOR) but enhanced
      that of JNK when inducing autophagy. We identified SPC as a switch for the
      activity of Akt1, a supposed upstream modulator of both mTOR and JNK.
      Furthermore, beta-cyclodextrin, which destroys membrane cholesterol, abolished
      the SPC-reduced phosphorylation of both Akt and PTEN, thus inhibiting SPC-induced
      autophagy. In conclusion, SPC is a novel molecule protecting cardiomyocytes
      against apoptosis by promoting autophagy. The lipid raft/PTEN/Akt1/mTOR signal
      pathway is the underlying mechanism and might provide novel targets for cardiac
      failure therapy. 

PMID- 25871971
TI  - Tryptase is involved in the development of early ventilator-induced pulmonary
      fibrosis in sepsis-induced lung injury.
AB  - INTRODUCTION: Most patients with sepsis and acute lung injury require mechanical
      ventilation to improve oxygenation and facilitate organ repair. Mast cells are
      important in response to infection and resolution of tissue injury. Since
      tryptase secreted from mast cells has been associated with tissue fibrosis, we
      hypothesized that tryptase would be involved in the early development of
      ventilator-induced pulmonary fibrosis in a clinically relevant model of sepsis
      induced lung injury. METHODS: Prospective, randomized, controlled animal study
      using Sprague-Dawley rats. Sepsis was induced by cecal ligation and perforation.
      Animals were randomized to spontaneous breathing or two ventilatory strategies
      for 4 h: protective ventilation with tidal volume (VT) = 6 ml/kg plus 10 cmH2O
      positive end-expiratory pressure (PEEP) or injurious ventilation with VT = 20
      ml/kg plus 2 cmH2O PEEP. Healthy, non-ventilated animals served as non-septic
      controls. We studied the following end points: histology, serum cytokine levels,
      hydroxyproline content, tryptase and proteinase-activated receptor-2 (PAR-2)
      protein level in lung homogenates, and tryptase and PAR-2 immunohistochemical
      localization in the lungs. RESULTS: All septic animals developed acute lung
      injury. Animals ventilated with high VT had a significant increase of pulmonary
      fibrosis, hydroxyproline content, tryptase and PAR-2 protein levels compared to
      septic controls (P <0.0001). However, protective ventilation attenuated sepsis
      induced lung injury and decreased lung tryptase and PAR-2 protein levels.
      Immunohistochemical staining confirmed the presence of tryptase and PAR-2 in the
      lungs. CONCLUSIONS: Mechanical ventilation modified tryptase and PAR-2 in injured
      lungs. Increased levels of these proteins were associated with development of
      sepsis and ventilator-induced pulmonary fibrosis early in the course of sepsis
      induced lung injury.

PMID- 25871972
TI  - No evidence for attenuated stress-induced extrastriatal dopamine signaling in
      psychotic disorder.
AB  - Stress is an important risk factor in the etiology of psychotic disorder.
      Preclinical work has shown that stress primarily increases dopamine (DA)
      transmission in the frontal cortex. Given that DA-mediated hypofrontality is
      hypothesized to be a cardinal feature of psychotic disorder, stress-related
      extrastriatal DA release may be altered in psychotic disorder. Here we quantified
      for the first time stress-induced extrastriatal DA release and the spatial extent
      of extrastriatal DA release in individuals with non-affective psychotic disorder
      (NAPD). Twelve healthy volunteers (HV) and 12 matched drug-free NAPD patients
      underwent a single infusion [(18)F]fallypride positron emission tomography scan
      during which they completed the control and stress condition of the Montreal
      Imaging Stress Task. HV and NAPD did not differ in stress-induced
      [(18)F]fallypride displacement and the spatial extent of stress-induced
      [(18)F]fallypride displacement in medial prefrontal cortex (mPFC) and temporal
      cortex (TC). In the whole sample, the spatial extent of stress-induced
      radioligand displacement in right ventro-mPFC, but not dorso-mPFC or TC, was
      positively associated with task-induced subjective stress. Psychotic symptoms
      during the scan or negative, positive and general subscales of the Positive and
      Negative Syndrome Scale were not associated with stress-induced [(18)F]fallypride
      displacement nor the spatial extent of stress-induced [(18)F]fallypride
      displacement in NAPD. Our results do not offer evidence for altered stress
      induced extrastriatal DA signaling in NAPD, nor altered functional relevance. The
      implications of these findings for the role of the DA system in NAPD and stress
      processing are discussed. 

PMID- 25871973
TI  - Alterations in frontal white matter neurochemistry and microstructure in
      schizophrenia: implications for neuroinflammation.
AB  - We investigated in vivo neurochemical markers reflective of neuronal health and
      glial activation to determine if these could yield clues regarding the reduced
      fractional anisotropy (FA) of white matter and accelerated decline of FA with age
      in schizophrenia. Participants with schizophrenia and healthy controls completed
      diffusion tensor imaging to assess FA and proton magnetic resonance spectroscopy
      to assess neurochemical metabolites in the same frontal region. Frontal FA was
      significantly lower in the schizophrenia and declined more rapidly with age
      compared with the healthy control group. In both groups, N-acetylaspartate (NAA),
      a putative marker of neuronal integrity, and glutamate declined with age, and
      this decline was stronger in patients. Myo-inositol, a marker of glial cells, was
      negatively related to FA in both groups. The relationship between FA and age
      remained significant in schizophrenia even when controlling for all metabolites.
      The relationships of FA, NAA and myo-inositol to age appear to be independent of
      one another. The relationship between FA and myo-inositol was independently
      present in both patients and controls, even after controlling for age, indicating
      a potential general effect of neuroinflammation on white matter microstructure.
      Further studies are warranted to determine the underlying mechanism driving the
      accelerated FA decline with age in schizophrenia. 

PMID- 25871974
TI  - Caffeine increases striatal dopamine D2/D3 receptor availability in the human
      brain.
AB  - Caffeine, the most widely consumed psychoactive substance in the world, is used
      to promote wakefulness and enhance alertness. Like other wake-promoting drugs
      (stimulants and modafinil), caffeine enhances dopamine (DA) signaling in the
      brain, which it does predominantly by antagonizing adenosine A2A receptors
      (A2AR). However, it is unclear if caffeine, at the doses consumed by humans,
      increases DA release or whether it modulates the functions of postsynaptic DA
      receptors through its interaction with adenosine receptors, which modulate them.
      We used positron emission tomography and [(11)C]raclopride (DA D2/D3 receptor
      radioligand sensitive to endogenous DA) to assess if caffeine increased DA
      release in striatum in 20 healthy controls. Caffeine (300 mg p.o.) significantly
      increased the availability of D2/D3 receptors in putamen and ventral striatum,
      but not in caudate, when compared with placebo. In addition, caffeine-induced
      increases in D2/D3 receptor availability in the ventral striatum were associated
      with caffeine-induced increases in alertness. Our findings indicate that in the
      human brain, caffeine, at doses typically consumed, increases the availability of
      DA D2/D3 receptors, which indicates that caffeine does not increase DA in the
      striatum for this would have decreased D2/D3 receptor availability. Instead, we
      interpret our findings to reflect an increase in D2/D3 receptor levels in
      striatum with caffeine (or changes in affinity). The association between
      increases in D2/D3 receptor availability in ventral striatum and alertness
      suggests that caffeine might enhance arousal, in part, by upregulating D2/D3
      receptors. 

PMID- 25871975
TI  - DEGS2 polymorphism associated with cognition in schizophrenia is associated with
      gene expression in brain.
AB  - A genome-wide association study of cognitive deficits in patients with
      schizophrenia in Japan found association with a missense genetic variant
      (rs7157599, Asn8Ser) in the delta(4)-desaturase, sphingolipid 2 (DEGS2) gene. A
      replication analysis using Caucasian samples showed a directionally consistent
      trend for cognitive association of a proxy single-nucleotide polymorphism (SNP),
      rs3783332. Although the DEGS2 gene is expressed in human brain, it is unknown how
      DEGS2 expression varies during human life and whether it is affected by
      psychiatric disorders and genetic variants. To address these questions, we
      examined DEGS2 messenger RNA using next-generation sequencing in postmortem
      dorsolateral prefrontal cortical tissue from a total of 418 Caucasian samples
      including patients with schizophrenia, bipolar disorder and major depressive
      disorder. DEGS2 is expressed at very low levels prenatally and increases
      gradually from birth to adolescence and consistently expressed across adulthood.
      Rs3783332 genotype was significantly associated with the expression across all
      subjects (F3,348=10.79, P=1.12 * 10(-)(3)), particularly in control subjects
      (F1,87=13.14, P=4.86 * 10(-4)). Similar results were found with rs715799
      genotype. The carriers of the risk-associated minor allele at both loci showed
      significantly lower expression compared with subjects homozygous for the non-risk
      major allele and this was a consistent finding across all diagnostic groups.
      DEGS2 expression showed no association with diagnostic status after correcting
      for multiple testing (P>0.05). Our findings demonstrate that a SNP showing genome
      wide association study significant association with cognition in schizophrenia is
      also associated with regulation of DEGS2 expression, implicating a molecular
      mechanism for the clinical association. 

PMID- 25871976
TI  - Novel insights into the behavioral analysis of mice subjected to the forced-swim
      test.
AB  - The forced-swim test (FST) is one of the most widely used rodent behavioral
      assays, in which the immobility of animals is used to assess the effectiveness of
      antidepressant drugs. However, the existing, and mostly arbitrary, criteria used
      for quantification could lead to biased results. Here we believe we uncovered new
      confounding factors, revealed new indices to interpret the behavior of mice and
      propose an unbiased means for quantification of the FST. 

PMID- 25871977
TI  - Spatial heterogeneity of plant-soil feedback affects root interactions and
      interspecific competition.
AB  - Plant-soil feedback is receiving increasing interest as a factor influencing
      plant competition and species coexistence in grasslands. However, we do not know
      how spatial distribution of plant-soil feedback affects plant below-ground
      interactions. We investigated the way in which spatial heterogeneity of soil
      biota affects competitive interactions in grassland plant species. We performed a
      pairwise competition experiment combined with heterogeneous distribution of soil
      biota using four grassland plant species and their soil biota. Patches were
      applied as quadrants of 'own' and 'foreign' soils from all plant species in all
      pairwise combinations. To evaluate interspecific root responses, species-specific
      root biomass was quantified using real-time PCR. All plant species suffered
      negative soil feedback, but strength was species-specific, reflected by a
      decrease in root growth in own compared with foreign soil. Reduction in root
      growth in own patches by the superior plant competitor provided opportunities for
      inferior competitors to increase root biomass in these patches. These patterns
      did not cascade into above-ground effects during our experiment. We show that
      root distributions can be determined by spatial heterogeneity of soil biota,
      affecting plant below-ground competitive interactions. Thus, spatial
      heterogeneity of soil biota may contribute to plant species coexistence in
      species-rich grasslands. 

PMID- 25871978
TI  - Description of a New Temnocephala Species (Platyhelminthes) from the Southern
      Neotropical Region.
AB  - The genus Temnocephala is endemic to the Neotropical region. Temnocephala
      mexicana and Temnocephala chilensis are the only 2 temnocephalans whose known
      distribution ranges extend to the south beyond Parallel 40 degrees S. No
      Temnocephala species has ever been recorded from the extensive area between
      Parallel 43 degrees S and the southern end of the South American continent, which
      makes the study of the southern limit of the distribution of the genus a topic of
      great interest. The southernmost report corresponds to T. chilensis from the
      Telsen River, Chubut Province, Argentina. In March 2000, several temnocephalans
      were found on the freshwater anomuran crustacean Aegla neuquensis from the same
      locality; the specimens were identified as belonging to a new species, which is
      described here. This species is characterized by possessing an unusually thin
      walled, narrow zone that has the appearance of a deep groove connecting the
      introvert to the shaft of the penial stylet; an introvert with 36 longitudinal
      rows of spines, each bearing 6-8 spines that are progressively smaller towards
      the distal end; a distal end of the introvert with a very thin, sclerotized wall
      without spines; a seminal vesicle that opens sub-polarly into the contractile
      vesicle; a pair of paranephrocytes at the level of the pharynx and a second pair
      at the level of the anterior portion of the anterior testes, and eggs with very
      long stalks. On the basis of their overall morphology, host preference, and
      geographical distribution, T. chilensis and the new species are closely related,
      so a diagnostic key for the southern species of Temnocephala is also included.
      The type locality of the new species is in the southern limit of the known
      distribution area of T. chilensis, so after this work there are 2 known species
      marking the southern limit of the distribution of the genus.

PMID- 25871979
TI  - Heat shock protein 90 associates with Toll-like receptors 7/9 and mediates self
      nucleic acid recognition in SLE.
AB  - Systemic lupus erythematosus (SLE) is a prototype systemic autoimmune disease,
      and disease activity is associated with serum IFN-alpha level. Plasmacytoid
      dendritic cells (pDCs) sense microbial as well as self-nucleic acids by TLRs 7
      and 9 and produce a large amount of IFN-alpha. Here, we show that heat shock
      protein 90 (Hsp90) associates with and delivers TLR7/9 from the ER to early
      endosomes for ligand recognition. Inhibition of Hsp90 by various approaches
      including the use of Hsp90 inhibitor, a geldanamycin derivative, suppressed the
      Hsp90 association with TLR7/9, which resulted in inhibition of IFN-alpha
      production, leading to improvement of SLE symptoms in mice. Notably, we observed
      that serum Hsp90 is clearly increased in patients with active SLE compared with
      that in patients with inactive disease. Furthermore, we demonstrated that serum
      Hsp90 detected in SLE patients binds to self-DNA and/or anti-DNA Ab, thus leading
      to stimulation of pDCs to produce IFN-alpha. Our data demonstrate that Hsp90
      plays a crucial role in the pathogenesis of SLE and that an Hsp90 inhibitor will
      therefore provide a new therapeutic approach to SLE and other nucleic acid
      related autoimmune diseases.

PMID- 25871980
TI  - Lymphoceles Post-Radical Retropubic Prostatectomy: A Retrospective Evaluation of
      Epidemiology, Risk Factors and Outcome.
AB  - INTRODUCTION: We aimed at evaluating the incidence of lymphoceles, a common
      complication after radical retropubic prostatectomy (RRP), at a high volume
      centre, define risk factors and assess the clinical outcome. MATERIALS AND
      METHODS: 454 patients receiving RRP and pelvic lymph node dissection were
      assessed for postoperative lymphoceles using the ultrasound method. Findings were
      correlated to clinical parameters from a database (age, BMI, initial PSA, number
      of lymph nodes removed, prostate weight, duration of surgery, hospital stay,
      duration of catheterisation) and possible unconventional risk factors using
      meteorological data. RESULTS: Overall, 15.4% developed a lymphocele, 2.6% had a
      symptomatic lymphocele requiring treatment. The mean size of the lymphoceles
      requiring treatment was significantly higher (400 vs. 115 ml). Patients with
      lymphocele stayed longer in hospital. No correlation could be found between the
      clinical parameters and the risk for lymphoceles. Functional results in terms of
      urinary continence were similar. The assessment of meteorological risk factors
      showed a correlation of lymphoceles with air humidity. CONCLUSION: Lymphoceles
      are common after RRP, but few cases require intervention. There is no reliable
      clinical predictor for the risk of lymphocele development. Data sets have been
      published suggesting several risk factors but may be subject to statistical error
      like in the case of the meteorological predictors in this study.

PMID- 25871981
TI  - The effect of expressive writing intervention on psychological and physical
      health outcomes in cancer patients--a systematic review and meta-analysis.
AB  - OBJECTIVE: This study aimed to evaluate the effectiveness of expressive writing
      intervention (EWI) for improving psychological and physical health in cancer
      patients and survivors. METHODS: We searched databases and existing reviews for
      randomized controlled studies published between 1986 and 2014 that evaluated the
      effects of EWI on psychological and physical health outcomes. We computed and
      combined effect sizes and examined the role of methodological characteristics.
      RESULTS: From 223 unique citations, we identified 16 independent randomized
      controlled trials published from 1999 to 2014, examining the effect of EWI on a
      range of psychological and physical health outcomes. No statistically significant
      effects were found for any of the individual or combined psychological (Hedges's
      g: 0.04; 95% CI, -0.06 to 0.14; p = 0.42), physical (0.08; 95% CI, -0.05 to 0.20;
      p = 0.22), or quality-of-life outcomes (0.09; 95% CI, -0.05 to 0.24; p = 0.22).
      The results were unaffected by differences in study characteristics, for example,
      type of control condition, study setting, cancer type, and overall study quality
      ratings. Results from a subset of studies indicated a possible moderating effect
      of social constraints, suggesting that participants experiencing low levels of
      emotional support may be more likely to benefit from EWI. CONCLUSIONS: Our
      results do not support the general effectiveness of EWI in cancer patients and
      survivors. However, given the practical and inexpensive intervention, it is
      possible that even small effects in subgroups of patients could be clinically
      relevant, and future studies are recommended to test the effects of potential
      moderators, including pre-intervention distress levels and context-dependent
      factors such as emotional support.

PMID- 25871982
TI  - Concerning Sichieri R, Cunha DB: Obes Facts 2014;7:221-232. The Assertion that
      Controlling for Baseline (Pre-Randomization) Covariates in Randomized Controlled
      Trials Leads to Bias is False.

PMID- 25871983
TI  - Paediatric intracranial anaplastic ependymoma: the role of multiple surgical
      resections for disease relapse in maintaining quality of life and prolonged
      survival.
AB  - INTRODUCTION: Ependymoma is the third most common intracranial glioma in
      children. The treatment of choice for these tumours remains gross total resection
      followed by radiotherapy. There are two principal histological subtypes, namely
      classic (~70%) and anaplastic (~30%) ependymoma. CASE: We present the case of a
      12-year-old girl with an anaplastic ependymoma of the left temporal lobe. She
      underwent initial image-guided resection following biopsy. A postoperative MRI
      showed a macroscopic resection. She subsequently relapsed and indeed had 11 local
      and distant relapses managed by 12 separate craniotomies and tumour resection, 4
      courses of radiotherapy and chemotherapy. CONCLUSION: For patients with multiple
      relapses, surgery should be considered primarily to re-resect any symptomatic
      lesion. This case demonstrates that multiple tumour resections can be undertaken
      with limited morbidity for the patient and with maintenance of quality of life.
      Repeated focal irradiation can also be used to control the disease with limited
      morbidity.

PMID- 25871984
TI  - To RIC or not to RIC: that is the question.

PMID- 25871985
TI  - Perceived discrimination in healthcare settings among Latinos with limited
      English proficiency in South Carolina.
AB  - OBJECTIVES: Perceived discrimination in healthcare settings is reported
      frequently by Latino adults and is associated with reductions in healthcare
      utilization and having a usual source of care. Little is known about
      discrimination perceived by Latino adults with limited English proficiency (LEP)
      who also frequently experience difficulties with healthcare access and
      utilization. The objective of this pilot study was to examine perceived
      discrimination in healthcare settings among Latino adults with LEP living in
      South Carolina. METHODS: Sixty-two Latino adults with LEP were surveyed to
      examine perceived discrimination in healthcare settings using the 10-question
      Behavioral Risk Factor Surveillance System Reactions to Race Module. RESULTS:
      Seventy percent of the sample reported thinking about race/ethnicity on a daily
      basis. Twenty-one percent reported experiencing physical symptoms and 26%
      reported feeling emotionally upset in the past 30 days based on how they were
      treated by others because of their race. When seeking healthcare services, only
      11.5% perceived discrimination in healthcare settings. CONCLUSIONS: Although a
      significant percentage of the sample reported thinking about race/ethnicity
      daily, only approximately 25% reported experiencing health symptoms based on how
      they were treated as a result of their race and few perceived discrimination in
      healthcare settings.

PMID- 25871986
TI  - A comparison of medical students' learning approaches between the first and
      fourth years.
AB  - OBJECTIVES: We hypothesized that medical students exposed to a case-based
      curriculum in years 1 and 2 and clinical cases in the year 3 clerkship would
      demonstrate a longitudinal increase in the deep approach to learning and a
      decrease in the surface apathetic approach. METHODS: A cohort of first-year
      medical students completed the Approaches and Study Skills Inventory for Students
      at the beginning of their first term and again at the beginning of their fourth
      year. Approaches and Study Skills Inventory for Students scores were aggregated
      into three main learning approach scales: deep, strategic, and surface apathetic.
      RESULTS: On average, deep and strategic scores did not significantly change
      between years 1 and 4, but the surface apathetic mean score decreased as a result
      of lower syllabus boundness and fear of failure subscale scores. Effect sizes
      were small (d = 0.30, 0.34, respectively). CONCLUSIONS: The deep approach to
      learning is a complex process and did not change in our students after 3 years of
      medical school, even though a case-based curriculum was believed to foster deeper
      learning. By the end of year 3, our students were, on average, less bound to
      syllabi and feared failure less.

PMID- 25871987
TI  - Commentary on "A comparison of medical students' learning approaches between the
      first and fourth years".

PMID- 25871988
TI  - Race, socioeconomic status, health-related quality of life, and self-care of type
      2 diabetes mellitus among adults in North Carolina.
AB  - OBJECTIVES: The objective of this study was to examine the associations among
      race, education, income, and health-related quality of life (HRQoL) in self-care
      of type 2 diabetes mellitus among adults in North Carolina. METHODS: A secondary
      analysis was conducted using data from the 2009 Behavioral Risk Factor
      Surveillance Survey (BRFSS), a large population-based survey (N = 432,607)
      conducted in the United States. The data were analyzed to account for the
      weighted complex multistage sampling design of the Behavioral Risk Factor
      Surveillance Survey. Parametric testing using univariate/bivariate/multivariate
      analysis was performed. RESULTS: The majority of participants reported taking a
      class/course on diabetes mellitus management and having checked their blood
      glucose levels at least once per day. The majority (61.26%) of the participants
      did not have good self-management skills, based on the education and blood
      glucose-monitoring criteria established for this study. Participants with poor
      HRQoL had significantly increased odds of good diabetes mellitus self-care
      practices. CONCLUSIONS: Individuals with poor HRQoL had significantly increased
      odds of good diabetes mellitus self-care practices. Although findings on race,
      education, and income were not statistically significant, they were consistent
      with previous research. In the future, individuals who are nonwhite, have less
      than a high school level of education, and have no health insurance should be
      targeted to improve diabetes mellitus self-care practices through educational and
      informational materials. Further investigation using more comprehensive measures
      of diabetes mellitus self-care is warranted.

PMID- 25871989
TI  - Commentary on "Race, socioeconomic status, health-related quality of life, and
      self-care of type 2 diabetes mellitus among adults in North Carolina".

PMID- 25871990
TI  - Advice on stroke provided by pharmacies in the United States: implications for
      treatment and care.
AB  - OBJECTIVES: Studies have found that some health lines and physician's offices
      have provided treatment advice other than "call 9-1-1 for an ambulance" to
      patients who present with a stroke scenario. We assessed the treatment advice
      given by selected pharmacies in the United States regarding stroke. METHODS: The
      investigators called 73 randomly selected pharmacies and informed respondents
      that the caller's mother had experienced stroke-like symptoms several days
      earlier. Respondents were asked what should be done if the symptoms returned in
      the future and then debriefed on the deception afterward. RESULTS: Seventy-one of
      the 73 pharmacies participated and only 20% (95% confidence interval 12-30) of
      respondents gave the ideal advice "call 9-1-1 for an ambulance." CONCLUSIONS: One
      out of every five pharmacy respondents across the United States recommended
      advice other than calling emergency medical services for a potential stroke
      scenario.

PMID- 25871991
TI  - Commentary on "Advice on stroke provided by pharmacies in the United States:
      implications for treatment and care".

PMID- 25871992
TI  - Beyond PSA: managing modern therapeutic options in metastatic castration
      resistant prostate cancer.
AB  - Prostate cancer remains a significant cause of cancer-related deaths in men in
      the United States. Significant advances in the treatment of metastatic castration
      resistant prostate cancer have been made in recent years with the arrival of new
      therapeutic targets and options. The definition of progression of disease must be
      thought of in the context of clinical symptoms and radiographic evidence rather
      than as changes in prostate-specific antigen (PSA). Ultimately, the use of PSA
      criteria alone should not be used to determine the progression of disease;
      instead, PSA should be evaluated in combination with other clinical data. 

PMID- 25871993
TI  - Commentary on "Beyond PSA: managing modern therapeutic options in metastatic
      castration-resistant prostate cancer".

PMID- 25871994
TI  - Outcomes of lobar and sublobar resections for non-small-cell lung cancer: a
      single-center experience.
AB  - OBJECTIVES: Lung cancer is the leading cause of cancer-related mortality in the
      United States. Kentucky has the highest age-adjusted lung cancer rate and has one
      of the highest death rates from lung cancer in the country. Lobectomy is
      considered the standard therapy for non-small-cell lung cancer (NSCLC), whereas
      sublobar resection remains an option for selected patients. We investigated
      outcomes in patients having standard resections for lung cancer (lobectomy)
      compared with those having sublobar resections in a population with high
      prevalence of, and with a high death rate from, lung cancer. METHODS: We studied
      patients having lung cancer resections at the University of Kentucky between 2002
      and 2007. We reviewed the records of 222 patients who had either lobar or
      sublobar resections for NSCLC. This retrospective review identified key outcome
      variables, as well as short- and long-term survival. Propensity analysis allowed
      outcome comparison between patients having lobar and sublobar resections matched
      for preoperative variables. RESULTS: Of the 222 study patients, 181 patients had
      lobectomies and 41 had sublobar resections. For all resections, lobectomy was
      associated with improved 1-, 3-, and 5-year survival rates compared with sublobar
      resections. Compared with patients having sublobar resections, lobectomy patients
      had significantly increased unadjusted perioperative morbidity (43.1% lobectomy
      vs 7.3% sublobar), but not mortality. After propensity analysis, sublobar
      resection predicted significantly reduced morbidity (6.3% vs 53.3%, P < 0.001),
      but not operative mortality (3.3% vs 3.3%, P = not significant), compared with
      lobectomy in patients matched for age, sex, cancer stage, and date of operation.
      Adjuvant chemotherapy combined with radiation therapy showed significantly
      improved long-term survival for either type of resection. Cox regression with
      adjustment for age, cancer stage, and postoperative complications suggested that
      neoadjuvant chemotherapy/radiotherapy increased long-term survival (P = 0.038,
      hazard ratio 0.49). CONCLUSIONS: Sublobar resections for NSCLC have less
      morbidity compared with lobectomy, but at the cost of decreased long-term
      survival. These results imply that surgeons select patients for lobar or sublobar
      resections based on physiologic and functional parameters, and that differences
      in outcomes between these two groups reflect this selection bias. We suspect that
      these results are typical of surgical treatment of NSCLC in a heterogeneous high
      risk population with a high penetration and prevalence of lung cancer.

PMID- 25871995
TI  - Effectiveness of a federal Healthy Start Program on HIV/AIDS risk reduction among
      women in Hillsborough County, Florida.
AB  - OBJECTIVES: To examine the impact of the Central Hillsborough Healthy Start
      Project (CHHS) on human immunodeficiency virus (HIV)/acquired immunodeficiency
      syndrome (AIDS) diagnosis rates in women in Hillsborough County, Florida.
      METHODS: Project records were linked to hospital discharge data and vital
      statistics (Florida, 1998-2007; N = 1,696,221). The chi(2) test was used to
      compare rates for HIV/AIDS and pregnancy-related complications for mothers within
      the CHHS service area with mothers in Hillsborough County and the rest of
      Florida. RESULTS: During a 10-year period, HIV/AIDS diagnosis rates among women
      in the CHHS service area declined by 56.3% (P = 0.01). The observed decline was
      most evident among black women. HIV/AIDS diagnosis rates in the rest of
      Hillsborough County and Florida remained unchanged (P = 0.48). CONCLUSIONS:
      Lessons learned from the CHHS Project can be used to develop effective and
      comprehensive models for addressing the HIV epidemic.

PMID- 25871996
TI  - Risks of sex hormone therapy in women: important lessons from the transgender
      woman literature.

PMID- 25871997
TI  - Authors' response.

PMID- 25871998
TI  - Sm(II)-Mediated Electron Transfer to Carboxylic Acid Derivatives: Development of
      Complexity-Generating Cascades.
AB  - Reductive electron transfer (ET) to organic compounds is a powerful method for
      the activation of substrates via the formation of radicals, radical anions,
      anions, and dianions that can be exploited in bond-cleaving and bond-forming
      processes. Since its introduction to the synthetic community in 1977 by Kagan,
      SmI2 has become one of the most important reducing agents available in the
      laboratory. Despite its widespread application in aldehyde and ketone reduction,
      it was widely accepted that carboxylic acid derivatives could not be reduced by
      SmI2; only recently has our work led to this dogma being overturned, and the
      reduction of carboxylic acid derivatives using SmI2 can now take its place
      alongside aldehyde/ketone reduction as a powerful activation mode for synthesis.
      In this Account, we set out our studies of the reduction of carboxylic acid
      derivatives using SmI2, SmI2-H2O, and SmI2-H2O-NR3 and the exploitation of the
      unusual radical anions that are now accessible in unprecedented carbon-carbon
      bond-forming processes. The Account begins with our serendipitous discovery that
      SmI2 mixed with H2O is able to reduce six-membered lactones to diols, a
      transformation previously thought to be impossible. After the successful
      development of selective monoreductions of Meldrum's acid and barbituric acid
      heterocyclic feedstocks, we then identified the SmI2-H2O-NR3 reagent system for
      the efficient reduction of a range of acyclic carboxylic acid derivatives that
      typically present a significant challenge for ET reductants. Mechanistic studies
      have led us to propose a common mechanism for the reduction of carboxylic acid
      derivatives using Sm(II), with only subtle changes observed as the carboxylic
      acid derivative and Sm(II) reagent system are varied. At the center of our
      postulated mechanism is the proposed reversibility of the first ET to the
      carbonyl of carboxylic acid derivatives, and this led us to devise several
      strategies that allow the radical anion intermediates to be exploited
      productively in efficient new processes. First, we have used internal directing
      groups in substrates to "switch on" productive ET to esters and amides and have
      exploited such an approach in tag-removal cyclization processes that deliver
      molecular scaffolds of significance in biology and materials science. Second, we
      have exploited external ligands to facilitate ET to carboxylic acid derivatives
      and have applied the strategy in telescoped reaction sequences. Finally, we have
      employed follow-up cyclizations with alkenes, alkynes, and allenes to intercept
      radical anion intermediates formed along the reaction path and have employed this
      strategy in complexity-generating cascade approaches to biologically significant
      molecular architectures. From our studies, it is now clear that Sm(II)-mediated
      ET to carboxylic acid derivatives constitutes a general strategy for inverting
      the polarity of the carbonyl, allowing nucleophilic carbon-centered radicals to
      be formed and exploited in novel chemical processes. 

PMID- 25871999
TI  - A high-performance liquid chromatography-tandem mass spectrometry-based targeted
      metabolomics kidney dysfunction marker panel in human urine.
AB  - BACKGROUND: Previous studies have examined and documented fluctuations in urine
      metabolites in response to disease processes and drug toxicity affecting
      glomerular filtration, tubule cell metabolism, reabsorption, oxidative stress,
      purine degradation, active secretion and kidney amino acylase activity
      representative of diminished renal function. However, a high-throughput assay
      that incorporates metabolites that are surrogate markers for such changes into a
      kidney dysfunction panel has yet to be described. METHODS: A high-performance
      liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) assay for the
      quantification of ten metabolites associated with the Krebs cycle, purine
      degradation, and oxidative stress in human urine was developed and validated.
      Normal values were assessed in healthy adult (n=120) and pediatric (n=36)
      individuals. In addition, 9 pediatric renal transplant recipients patients were
      evaluated before and after initial dosing of the immunosuppressant tacrolimus in
      a proof-of-concept study. RESULTS: The assay met all predefined acceptance
      criteria. The lower limit of quantification ranged from 0.1 to 1000 MUmol/l.
      Inter-day trueness and imprecisions ranged from 91.4-112.9% and 1.5-12.4%,
      respectively. The total assay run time was 5.5 minutes. Concentrations of
      glucose, sorbitol, and trimethylamine oxide (TMAO) were elevated in pediatric
      renal transplant patients (n=9) prior to transplantation as well as before and
      immediately after initial dosing of tacrolimus. One month post-transplant urine
      metabolite patterns matched those of healthy children (n=36). CONCLUSIONS: The LC
      MS/MS assay will provide the basis for further large-scale clinical studies to
      explore these analytes as molecular markers for the patients with renal
      insufficiency.

PMID- 25872002
TI  - Addition of eGFR and Age Improves the Prognostic Absolute Renal Risk-Model in
      1,134 Norwegian Patients with IgA Nephropathy.
AB  - BACKGROUND: Predicting outcome in individual patients with IgA nephropathy (IgAN)
      is difficult but important. For this purpose, the absolute renal risk (ARR) model
      has been developed in a French cohort to calculate the risk of end-stage renal
      disease (ESRD) and death. ARR (0-3) is scored in individual IgAN patients based
      on the presence of proteinuria >=1 g/24 h, hypertension, and severe
      histopathological lesions (1 point per risk factor). We have validated the ARR
      model in a Norwegian cohort of IgAN patients and tested whether adding data on
      initial estimated glomerular filtration rate (eGFR) and age improved prediction.
      METHODS: IgAN patients diagnosed between 1988 and 2012 were identified in the
      Norwegian Kidney Biopsy Registry, and endpoints were identified by record linkage
      with the Norwegian Renal Registry (ESRD) and the Population Registry (deaths).
      RESULTS: We identified 1,134 IgAN patients. The mean duration of follow-up was
      10.2 years (range 0.0 to 25.7 years). Two hundred and fifty one patients
      developed ESRD and there were 69 pre-ESRD deaths. The ARR model significantly
      stratified the IgAN cohort according to risk of ESRD/death. The inclusion of eGFR
      and age significantly improved the ARR prognostic model; in the receiver operator
      characteristics (ROC) analysis, area under the curve (AUC) at 10-years of follow
      up increased from 0.79 to 0.89, p < 0.001. CONCLUSIONS: ARR is a suitable
      prognostic model for stratifying IgAN patients according to the risk of ESRD or
      death. Including initial eGFR and age in the model substantially improved its
      accuracy in our nationwide cohort.

PMID- 25872003
TI  - Systematic review and meta-analysis of somatostatin analogues in the prevention
      of postoperative complication after pancreaticoduodenectomy.
AB  - BACKGROUND: The use of somatostatin analogues (SAs) following
      pancreaticoduodenectomy (PD) is controversial. METHOD: Literature databases were
      searched systematically for relevant articles. A meta-analysis of all randomized
      controlled trials (RCTs) evaluating prophylactic SAs in PD was performed.
      RESULTS: Fifteen RCTs involving 1,352 patients were included. There was a towards
      reduced incidences of pancreatic fistulas (p = 0.26), clinically significant
      pancreatic fistulas (p = 0.08), and bleeding (p = 0.05) in prophylactic SAs
      group. In subgroup analyses, prophylactic somatostatin significantly reduced the
      incidence of pancreatic fistulas(p = 0.02), with a nonsignificant trend toward
      reduced incidence of clinically significantly pancreatic fistulas (p =
      0.06).Pasireotide significantly reduced the incidence of clinically significantly
      pancreatic fistulas (p = 0.03). Octreotide had no influence on the incidence of
      pancreatic fistulas. CONCLUSION: The current best evidence suggests prophylactic
      treatment with somatostatin or pasireotide has a potential role in reducing the
      incidence of pancreatic fistulas, while octreotide had no influence on the
      incidence of pancreatic fistulas.High-quality RCTs assessing the role of
      somatostatin and pasireotide are required for further verification.

PMID- 25872004
TI  - Phosphatase activity and its relationship with physical and chemical parameters
      during vermicomposting of filter cake and cattle manure.
AB  - BACKGROUND: Recycling of phosphorus (P) from organic residues (ORs) is important
      to develop environmentally friendly agriculture. The use of this P source depends
      on phosphatase enzymes, which can be affected by a chain of parameters during
      maturation of ORs. In this study the phosphatase activity levels throughout
      vermicomposting of filter cake (FC) and cattle manure (CM) were correlated with
      different physical and chemical parameters in an effort to increase the knowledge
      about recycling of P from ORs. RESULTS: FC presented higher total nitrogen
      content (TNC), total organic carbon (TOC), humic acid (HA) content, water-soluble
      P (WSP), phosphatase activities and nanopore volume than CM during
      vermicomposting. Decreases in TOC of CM resulted from carbohydrate
      mineralization, which was not observed for FC. CM showed increased hydrophobic
      index during vermicomposting while FC showed a slight decrease. CONCLUSION:
      Phosphatase activities correlated positively with TOC, pH and WSP and negatively
      with HA content for both vermicomposts. Nanopore volume was negatively correlated
      with phosphatase activities for FC but not for CM. No correlations between
      hydrophobicity and phosphatase activities were found for FC. Increased
      hydrophobicity throughout vermicomposting of CM could be partially associated
      with decreases in phosphatase levels.

PMID- 25872005
TI  - Systemic Aldosterone, But Not Angiotensin II, Plays a Pivotal Role in the
      Pathogenesis of Renal Injury in Chronic Nitric Oxide-Deficient Male Rats.
AB  - Chronic inhibition of nitric oxide synthase by N(omega)-nitro-L-arginine methyl
      ester (L-NAME) causes progressive renal injury and systemic hypertension.
      Angiotensin II (Ang II) has been conventionally regarded as one of the primary
      causes of renal injury. We reported previously that such renal injury was almost
      completely suppressed by both an Ang II type I receptor blocker and an
      aldosterone antagonist. The aldosterone antagonist also inhibited the systemic
      Ang II elevation. Therefore, it remains to be elucidated whether Ang II or
      aldosterone directly affects the development of such renal injury. In the present
      study, we investigated the role of aldosterone in the pathogenesis of renal
      injury induced by L-NAME-mediated chronic nitric oxide synthase inhibition in
      male Wistar rats (aged 10 wk). Serial analyses demonstrated that the renal injury
      and inflammation in L-NAME-treated rats was associated with elevation of both Ang
      II and aldosterone. To investigate the direct effect of aldosterone on the renal
      injury, we conducted adrenalectomy (ADX) and aldosterone supplementation in L
      NAME-treated rats. In ADX rats, aldosterone was undetectable, and renal injury
      and inflammation were almost completely prevented by ADX, although systemic and
      local Ang II and blood pressure were still elevated. Aldosterone supplementation
      reversed the beneficial effect of ADX. The present study indicates that
      aldosterone rather than Ang II plays a central and direct role in the
      pathogenesis of renal injury by L-NAME through inflammation, independent of its
      systemic hemodynamic effects. 

PMID- 25872007
TI  - An Essential Role for Parathyroid Hormone in Gill Formation and Differentiation
      of Ion-Transporting Cells in Developing Zebrafish.
AB  - In vertebrates, parathyroid hormone (PTH) is important for skeletogenesis and
      Ca(2+) homeostasis. However, little is known about the molecular mechanisms by
      which PTH regulates skeleton formation and Ca(2+) balance during early
      development. Using larval zebrafish as an in vivo model system, we determined
      that PTH1 regulates the differentiation of epithelial cells and the development
      of craniofacial cartilage. We demonstrated that translational gene knockdown of
      PTH1 decreased Ca(2+) uptake at 4 days after fertilization. We also observed that
      PTH1-deficient fish exhibited reduced numbers of epithelial Ca(2+) channel (ecac)
      expressing cells, Na(+)/K(+)-ATPase-rich cells, and H(+)-ATPase-rich cells.
      Additionally, the density of epidermal stem cells was decreased substantially in
      the fish experiencing PTH1 knockdown. Knockdown of PTH1 caused a shortening of
      the jaw and impeded the development of branchial arches. Results from in situ
      hybridization suggested that the expression of collagen 2a1a (marker for
      proliferating chondrocytes) was substantially reduced in the cartilage that forms
      the jaw and branchial aches. Disorganization of chondrocytes in craniofacial
      cartilage also was observed in PTH1-deficient fish. The results of real-time PCR
      demonstrated that PTH1 morphants failed to express the transcription factor glial
      cell missing 2 (gcm2). Coinjection of PTH1 morpholino with gcm2 capped RNA
      rescued the phenotypes observed in the PTH1 morphants, suggesting that the
      defects in PTH1-deficient fish were caused, at least in part, by the suppression
      of gcm2. Taken together, the results of the present study reveal critical roles
      for PTH1 in promoting the differentiation of epidermal stem cells into mature
      ionocytes and cartilage formation during development. 

PMID- 25872006
TI  - Circadian Control of the Female Reproductive Axis Through Gated Responsiveness of
      the RFRP-3 System to VIP Signaling.
AB  - Throughout most of the ovulatory cycle, estrogen negative feedback restrains the
      GnRH neuronal system. Just before ovulation, however, estrogen negative feedback
      is removed to permit stimulation of the preovulatory GnRH/LH surge (positive
      feedback) by the circadian clock in the suprachiasmatic nucleus (SCN). The
      mammalian ortholog of avian gonadotropin-inhibitory hormone, RFamide-related
      peptide 3 (RFRP-3), participates in the circadian-timed removal of estrogen
      negative feedback to permit the LH surge. The present study examined the specific
      neurochemical means by which the SCN controls RFRP-3 activity and explored
      whether the RFRP-3 system exhibits time-dependent responsiveness to SCN signaling
      to precisely time the LH surge. We found that RFRP-3 cells in female Syrian
      hamsters (Mesocricetus auratus) receive close appositions from SCN-derived
      vasopressin-ergic and vasoactive intestinal peptide (VIP)-ergic terminal fibers.
      Central VIP administration markedly suppressed RFRP-3 cellular activity in the
      evening, but not the morning, relative to saline controls, whereas vasopressin
      was without effect at either time point. Double-label in situ hybridization for
      Rfrp-3 and the VIP receptors VPAC1 and VPAC2 revealed that the majority of RFRP-3
      cells do not coexpress either receptor in Syrian hamsters or mice, suggesting
      that SCN VIP-ergic signaling inhibits RFRP-3 cells indirectly. The timing of this
      VIP-mediated disinhibition is further coordinated via temporally gated
      responsiveness of RFRP-3 cells to circadian signaling. Together, these findings
      reveal a novel circadian hierarchy of control coordinating the preovulatory LH
      surge and ovulation. 

PMID- 25872009
TI  - Effect of Angiotensin receptor blockers on flow-mediated vasodilation: a meta
      analysis of randomized controlled trials.
AB  - BACKGROUND: In a meta-analysis, we investigated the effects of angiotensin
      receptor blockers (ARBs) in comparison to placebo or other classes of
      antihypertensive drugs on endothelial function, which was measured by brachial
      flow-mediated vasodilation (FMD). METHODS: We searched for randomized controlled
      trials that compared ARBs with placebo or other classes of antihypertensive drugs
      in improving FMD. A random-effect model was used to compute pooled estimates.
      RESULTS: In 13 trials (n = 529), ARBs were more efficacious in improving brachial
      FMD than placebo [pooled weighted mean change difference (WMD) 1.34%, 95% CI,
      0.93-1.75%, p<0.001]. In 15 trials (n = 918), treatment with ARBs had a
      significant effect on brachial FMD when compared with other antihypertensive
      drugs (pooled WMD 0.59%, 95% CI, 0.20-0.98%, p = 0.003 with significant
      heterogeneity). ARBs were also more efficacious in improving brachial FMD than
      calcium channel blockers (CCBs; pooled WMD 1.61%, 95% CI, 0.72-2.49%, p < 0.001)
      but not the other classes of drugs (p >= 0.072). CONCLUSIONS: This meta-analysis
      shows that ARBs improve brachial FMD, a marker of endothelial function, and that
      they are superior to placebo and CCBs. There was no significant difference in the
      effect on brachial FMD between ARBs and the other antihypertensive drugs.

PMID- 25872008
TI  - Magnetic Levitational Assembly for Living Material Fabrication.
AB  - Functional living materials with microscale compositional topographies are
      prevalent in nature. However, the creation of biomaterials composed of living
      micro building blocks, each programmed by composition, functionality, and shape,
      is still a challenge. A powerful yet simple approach to create living materials
      using a levitation-based magnetic method is presented. 

PMID- 25872010
TI  - Spontaneous eye movements and trait empathy predict vicarious learning of fear.
AB  - Learning to predict dangerous outcomes is important to survival. In humans, this
      kind of learning is often transmitted through the observation of others'
      emotional responses. We analyzed eye movements during an observational/vicarious
      fear learning procedure, in which healthy participants (N=33) watched another
      individual ('learning model') receiving aversive treatment (shocks) paired with a
      predictive conditioned stimulus (CS+), but not a control stimulus (CS-).
      Participants' gaze pattern towards the model differentiated as a function of
      whether the CS was predictive or not of a shock to the model. Consistent with our
      hypothesis that the face of a conspecific in distress can act as an unconditioned
      stimulus (US), we found that the total fixation time at a learning model's face
      increased when the CS+ was shown. Furthermore, we found that the total fixation
      time at the CS+ during learning predicted participants' conditioned responses
      (CRs) at a later test in the absence of the model. We also demonstrated that
      trait empathy was associated with stronger CRs, and that autistic traits were
      positively related to autonomic reactions to watching the model receiving the
      aversive treatment. Our results have implications for both healthy and
      dysfunctional socio-emotional learning. 

PMID- 25872011
TI  - Experimental and Computational Studies of the Kinetics of the Reaction of Atomic
      Hydrogen with Methanethiol.
AB  - The overall rate constant for H + CH3SH has been studied over 296-1007 K in an Ar
      bath gas using the laser flash photolysis method at 193 nm. H atoms were
      generated from CH3SH and in some cases NH3. They were detected via time-resolved
      resonance fluorescence. The results are summarized as k = (3.45 +/- 0.19) * 10(
      11) cm(3) molecule(-1) s(-1) exp(-6.92 +/- 0.16 kJ mol(-1)/RT) where the errors
      in the Arrhenius parameters are the statistical uncertainties at the 2sigma
      level. Overall error limits of +/-9% for k are proposed. In the overlapping
      temperature range there is very good agreement with the resonance fluorescence
      measurements of Wine et al. Ab initio data and transition state theory yield
      moderate accord with the total rate constant, but not with prior mass
      spectrometry measurements of the main product channels leading to CH3S + H2 and
      CH3 + H2S by Amano et al. 

PMID- 25872012
TI  - Rebound Thrombocytosis following Induction Chemotherapy is an Independent
      Predictor of a Good Prognosis in Acute Myeloid Leukemia Patients Attaining First
      Complete Remission.
AB  - There are very few data about the relationship between acute myeloid leukemia
      (AML) prognosis and bone marrow recovery kinetics following chemotherapy. In this
      study, we aimed to assess the prognostic importance and clinical associations of
      neutrophil and platelet recovery rates and rebound thrombocytosis (RT) or
      neutrophilia (RN) in the postchemotherapy period for newly diagnosed AML
      patients. De novo AML patients diagnosed between October 2002 and December 2013
      were evaluated retrospectively. One hundred patients were suitable for inclusion.
      Cox regression analysis using need for reinduction chemotherapy as a
      stratification parameter revealed RT as the only parameter predictive of OS, with
      borderline statistical significance (p = 0.06, OR = 7; 95% CI 0.92-53), and it
      was the only parameter predictive of DFS (p = 0.024, OR = 10; 95% CI 1.3-75). In
      order to understand whether RT or RN was related to a better marrow capacity or
      late consolidation, we considered neutrophil recovery time and platelet recovery
      time and nadir-first consolidation durations in all patients in the cohort. Both
      the marrow recovery duration and the time between marrow aplasia and first
      consolidation were shorter in RT and RN patients. To our knowledge, this is the
      first study to report a correlation between RT/RN and prognosis in AML.

PMID- 25872013
TI  - Let It "B"? The role of Hepatitis B universal vaccination among italian
      problematic drug users.
AB  - Hepatitis B virus (HBV) hepatitis is extremely common among problematic drug
      users (DUs). As of 2012, 47 of the 53 European countries had implemented a
      universal hepatitis B vaccination programme, a scenario that could radically
      change its spread. Even so, drug users are still one of the main groups at risk
      of being infected by HBV, exposing the fact that universal vaccination still has
      not managed to reach an optimal level of contagion protection. In order to
      evaluate the role of universal HBV vaccination in protecting against risk
      behaviour related to the use of illicit drugs, a group of 748 DUs, 511 male and
      237 female, was tested for HBV markers, at their first access to public addiction
      clinics in the metropolitan area of Bologna, Italy. 487 were born after 1981, so
      they were eligible to have received HBV vaccination in adolescence or at birth;
      in these subjects antibodies against HBV core antigen had the significant
      prevalence of 6.2%. Universal HBV vaccination has shown evidence of protecting
      against infection in the general population. These results, amongst the first to
      evaluate actual protection in DUs vaccinated at birth or during adolescence, show
      that compulsory universal vaccination does not solve the problem of HBV
      transmission in the most at risk groups and that additional strategies must be
      studied and implemented to address this issue. 

PMID- 25872014
TI  - Exposure to indoor pollutants and Wheeze and asthma development during early
      childhood.
AB  - BACKGROUND: This review aimed to summarize existing epidemiological evidence of
      the association between quantitative estimates of indoor air pollution with early
      childhood respiratory disease. METHODS: We carried out a systematic literature
      search of peer-reviewed epidemiological studies undertaken in "westernized"
      countries that have assessed exposure to indoor pollutants and asthma and wheeze
      from infancy up to the age of 5. RESULTS: The search, between January 2004 and
      February 2014 yielded 1840 studies for consideration. Following application of
      eligibility criteria to titles and abstracts 22 independent studies were deemed
      relevant for further review. Two additional studies were next identified through
      examination of the references' lists of these studies. Of these 24 selected
      studies, 16 adopted a prospective cohort design and 8 were case-control studies.
      Fourteen studies assessed exposure to bio-aerosols, 8 studies assessed exposure
      to specific air chemicals and two studies assessed exposure to bio-aerosols and
      air chemicals. Furthermore, 11 studies examined the association of exposure with
      asthma and 16 with wheeze. Findings indicate that existing studies have reported
      contradictory effects of indoor pollutants levels and occurrence of
      asthma/wheeze. CONCLUSION: Additional research to establish causality and
      evaluate interventions to prevent disease onset is needed.

PMID- 25872015
TI  - Evaluating physical and perceptual responses to exergames in Chinese children.
AB  - PURPOSE: The primary objective of this study was to examine whether exergames
      could help children reach the recommendations for PA and cardiorespiratory
      fitness regarding exercise intensity. Differences in perceived physical exertion,
      EE, VO2, and HR between normal weight (NW) and overweight (OW) children
      participating in exergames were also examined. METHODS: Twenty-one children (age:
      10.45 +/- 0.88) were assessed for EE, VO2 and HR during rest, in a maximal
      treadmill test, and while playing different exergames. Ratings of perceived
      exertion (RPE) (category range: 0 to 10) were also measured during exergaming.
      Three types of exergames were examined: running, table tennis, and dancing. These
      games were either performed on a Chinese game console, I-Dong, or another well
      developed Western game console (Sony PlayStation 3 or Nintendo Wii). RESULTS:
      Exergaming resulted in EE (kcal/min) from 2.05-5.14, VO2 (mL/kg/min) from 9.98
      25.54, and HR (beats per minute) from 98.05-149.66. Children reported RPE ranging
      from 1.29 to 5.29. The Chinese exergame, I-Dong Running, was the only game in
      which children reached a moderate intensity and met the recommended minimum
      VO2reserve (50%) for cardiorespiratory fitness. CONCLUSION: Exergames could
      provide alternative opportunities to enhance children's physical activity. They
      could be used as light-to-moderate PA, and with exergames, children can even
      reach the recommended intensity for developing and maintaining cardiorespiratory
      fitness.

PMID- 25872016
TI  - Chemical characterisation of the coarse and fine particulate matter in the
      environment of an underground railway system: cytotoxic effects and oxidative
      stress-a preliminary study.
AB  - BACKGROUND: Exposure to the particulate matter produced in underground railway
      systems is arousing increasing scientific interest because of its health effects.
      The aim of our study was to evaluate the airborne concentrations of PM10 and
      three sub-fractions of PM2.5 in an underground railway system environment in
      proximity to platforms and in underground commercial areas within the system, and
      to compare these with the outdoor airborne concentrations. We also evaluated the
      metal components, the cytotoxic properties of the various fractions of
      particulate matter (PM) and their capacity to induce oxidative stress. METHOD: We
      collected the coarse fraction (5-10 um) and the fine fractions (1-2.5 um; 0.5-1
      um; 0.25-0.5 um). Chemical characterisation was determined by means of
      spectrometry. Cytotoxicity and oxidative stress were evaluated by 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and Reactive
      Oxygen Species (ROS) assessment. RESULTS: The concentrations of both PM10 and
      PM2.5 proved to be similar at the three sampling sites. Iron and other transition
      metals displayed a greater concentration at the subway platform than at the other
      two sites. The 2.5-10 um and 1-2.5 um fractions of PM from all three sampling
      sites determined a greater increase in ROS; the intensity of oxidative stress
      progressively declined as particle diameter diminished. Moreover, ROS
      concentrations were correlated with the concentrations of some transition metals,
      namely Mn, Cr, Ti, Fe, Cu, Zn, Ni and Mo. All particulate matter fractions
      displayed lower or similar ROS values between platform level and the outdoor air.
      CONCLUSIONS: The present study revealed that the underground railway environment
      at platform level, although containing higher concentrations of some particularly
      reactive metallic species, did not display higher cytotoxicity and oxidative
      stress levels than the outdoor air.

PMID- 25872018
TI  - Health care workers' knowledge, attitudes and practices on tobacco use in
      economically disadvantaged dominican republic communities.
AB  - Tobacco use is increasing globally, particularly in low and middle-income
      countries like the Dominican Republic (DR) where data have been lacking. Health
      care worker (HCW) interventions improve quit rates; asking patients about tobacco
      use at each visit is an evidence-based first step. This study provides the first
      quantitative examination of knowledge, attitudes and practices of DR HCWs
      regarding tobacco use. All HCWs (N = 153) in 7 economically disadvantaged DR
      communities were targeted with anonymous surveys. Approximately 70% (N = 107)
      completed the primary outcome item, asking about tobacco use at each encounter.
      Despite >85% strongly agreeing that they should ask about tobacco use at each
      encounter, only 48.6% reported doing so. While most (94.39%) strongly agreed that
      smoking is harmful, knowledge of specific health consequences varied from 98.13%
      for lung cancer to 41.12% for otitis media. Few received training in tobacco
      intervention (38.32%). Exploratory analyses revealed that always asking even if
      patients are healthy, strongly agreeing that tobacco causes cardiac disease, and
      always advising smoke-free homes were associated with always asking. Overall,
      results demonstrate a disconnect between HCW belief and practice. Though most
      agreed that always asking about tobacco was important, fewer than half did so.
      Gaps in HCW knowledge and practices suggest a need for education and
      policy/infrastructure support. To our knowledge, this is the first reported
      survey of DR HCWs regarding tobacco, and provides a foundation for future tobacco
      control in the DR. 

PMID- 25872017
TI  - Emergency hospital visits in association with volcanic ash, dust storms and other
      sources of ambient particles: a time-series study in Reykjavik, Iceland.
AB  - Volcanic ash contributed significantly to particulate matter (PM) in Iceland
      following the eruptions in Eyjafjallajokull 2010 and Grimsvotn 2011. This study
      aimed to investigate the association between different PM sources and emergency
      hospital visits for cardiorespiratory causes from 2007 to 2012. Indicators of
      PM10 sources; "volcanic ash", "dust storms", or "other sources" (traffic,
      fireworks, and re-suspension) on days when PM10 exceeded the daily air quality
      guideline value of 50 ug/m3 were entered into generalized additive models,
      adjusted for weather, time trend and co-pollutants. The average number of daily
      emergency hospital visits was 10.5. PM10 exceeded the air quality guideline value
      115 out of 2191 days; 20 days due to volcanic ash, 14 due to dust storms (two
      days had both dust storm and ash contribution) and 83 due to other sources. High
      PM10 levels from volcanic ash tended to be significantly associated with the
      emergency hospital visits; estimates ranged from 4.8% (95% Confidence Interval
      (CI): 0.6, 9.2%) per day of exposure in unadjusted models to 7.3% (95% CI: -0.4,
      15.5%) in adjusted models. Dust storms were not consistently associated with
      daily emergency hospital visits and other sources tended to show a negative
      association. We found some evidence indicating that volcanic ash particles were
      more harmful than particles from other sources, but the results were inconclusive
      and should be interpreted with caution. 

PMID- 25872019
TI  - Community-based research as a mechanism to reduce environmental health
      disparities in american Indian and alaska native communities.
AB  - Racial and ethnic minority communities, including American Indian and Alaska
      Natives, have been disproportionately impacted by environmental pollution and
      contamination. This includes siting and location of point sources of pollution,
      legacies of contamination of drinking and recreational water, and mining,
      military and agricultural impacts. As a result, both quantity and quality of
      culturally important subsistence resources are diminished, contributing to poor
      nutrition and obesity, and overall reductions in quality of life and life
      expectancy. Climate change is adding to these impacts on Native American
      communities, variably causing drought, increased flooding and forced relocation
      affecting tribal water resources, traditional foods, forests and forest
      resources, and tribal health. This article will highlight several extramural
      research projects supported by the United States Environmental Protection Agency
      (USEPA) Science to Achieve Results (STAR) tribal environmental research grants as
      a mechanism to address the environmental health inequities and disparities faced
      by tribal communities. The tribal research portfolio has focused on addressing
      tribal environmental health risks through community based participatory research.
      Specifically, the STAR research program was developed under the premise that
      tribal populations may be at an increased risk for environmentally-induced
      diseases as a result of unique subsistence and traditional practices of the
      tribes and Alaska Native villages, community activities, occupations and customs,
      and/or environmental releases that significantly and disproportionately impact
      tribal lands. Through a series of case studies, this article will demonstrate how
      grantees-tribal community leaders and members and academic collaborators-have
      been addressing these complex environmental concerns by developing capacity,
      expertise and tools through community-engaged research. 

PMID- 25872020
TI  - Occupational exposure of diesel station workers to BTEX compounds at a bus depot.
AB  - Diesel fuel is known to emit pollutants that have a negative impact on
      environmental and human health. In developing countries like South Africa,
      attendants are employed to pump fuel for customers at service stations.
      Attendants refuel vehicles with various octane unleaded fuel, lead-replacement
      petrol and diesel fuel, on a daily basis. Attendants are at risk to adverse
      health effects associated with the inhalation of volatile organic compounds
      released from these fuels. The pollutants released include benzene, toluene,
      ethylbenzene and xylenes (BTEX), which are significant due to their high level of
      toxicity. In this study, a risk assessment of BTEX was conducted at a diesel
      service station for public buses. Using Radiello passive samplers, it was found
      that benzene concentrations were above recommended international standards. Due
      to poor ventilation and high exposure duration, the average benzene concentration
      over the sampling campaign exceeded the US Environmental Protection Agency's
      chronic inhalation exposure reference concentration. Lifetime cancer risk
      estimation showed that on average there is a 3.78 * 10-4 cancer risk,
      corresponding to an average chronic daily intake of 1.38 * 10-3 mg/kg/day of
      benzene exposure. Additionally, there were incidences where individuals were at
      potential hazard risk of benzene and toluene that may pose non-carcinogenic
      effects to employees. 

PMID- 25872021
TI  - Regarding the quantification of peripheral microcirculation--Comparing responses
      evoked in the in vivo human lower limb by postural changes, suprasystolic
      occlusion and oxygen breathing.
AB  - The human skin is an interesting model to explore microcirculation, particularly
      if using noninvasive technologies such as LDF (Laser Doppler Flowmetry) and tc
      (transcutaneous) gasimetry and methods as near as possible from the normal
      physiological state. In this study, we combined those technologies with three
      classical approaches--leg raising from supine, suprasystolic occlusion (in the
      ankle), and normobaric oxygen breathing to explore distal peripheral circulation
      in the foot. These methods are often cited, but a comparative assessment has not
      been done. The goal of this study was to identify relevant flow related
      descriptors, method-related advantages and pitfalls, and eventually, to find the
      best experimental approach. Volunteers (both genders, 22.1 +/- 3.7 years old)
      were subjected to these methods and variables registered during basal, challenge
      and stabilization phases. Descriptive and comparative statistics were obtained,
      adopting a 95% confidence level. All flow-related quantitative descriptors
      potentially useful for the analysis were identified and compared. As expected,
      male patients consistently showed higher LDF levels and transepidermal water loss
      (TEWL) and lower tcpO2 values. However, lower results were recorded in the supine
      position, suggesting a postural dependence. Both leg raising and suprasystolic
      occlusion produced a hyperemic response after provocation, although different in
      magnitude, significantly reducing LDF and tcpO2 during provocation. The oxygen
      breathing method provided the most patient-friendly protocol, consistently
      reducing LDF (potentially by the inhibition of production of local vasodilators).
      TEWL increased during the provocation phase in all protocols, although not
      significantly. Baseline tcpO2 was found to correlate positively with the peak
      tcpO2 during oxygen breathing and basal LDF with peak flow during leg raising and
      suprasystolic occlusion. No statistical correlation between TEWL and LDF could be
      demonstrated under the current experimental conditions. We conclude that although
      equally useful considering the purpose, these methods involve very different
      practicalities and do not provide the same information. Also noteworthy, LDF is a
      highly sensitive indicator that could be further explored to look deeper into
      blood flow regulating mechanisms.

PMID- 25872022
TI  - Advanced gastric cancer with liver and lymph node metastases successfully
      resected after induction chemotherapy with docetaxel, cisplatin and 5
      fluorouracil.
AB  - BACKGROUND: At diagnosis, about 35% of patients with gastric cancer present with
      distant metastases, and most patients with gastric cancer and liver metastases
      are excluded from curative surgery. CASE: We report a case of human epidermal
      growth factor receptor-2 (HER2)-negative gastric cancer with metastases to the
      liver and perigastric lymph nodes. The patient (a 60-year-old man) was considered
      unresectable at diagnosis and was treated with palliative chemotherapy (docetaxel
      plus cisplatin and 5-fluorouracil by continuous intravenous infusion over 5 days
      every 3 weeks). However, after 6 courses of chemotherapy, a computed tomography
      scan showed a reduction of the liver metastasis and the disappearance of the
      enlarged perigastric lymph nodes. The patient then underwent a curative
      gastrectomy, lymphadenectomy and liver resection. After surgery, the patient was
      treated with 6 courses of FOLFOX-4 regimen as adjuvant chemotherapy. With a
      follow-up of 26 months after surgery, the patient is alive and disease free.
      CONCLUSION: In patients with metastatic gastric cancer, the prognosis is poor
      with a median overall survival of 11 months since curative treatments are
      excluded; however, this case illustrated that a personalized treatment with
      chemotherapy and surgery can allow a curative strategy in selected patients with
      HER2-negative advanced gastric cancer.

PMID- 25872023
TI  - Platelet indices may be correlated with severity of vasospastic disorders.
AB  - BACKGROUND Vasospastic disorders are common worldwide. In daily practice, routine
      blood samples are used for several investigations. In this study we aimed to
      determine the possible correlations between lymphocyte count, platelet indices,
      and the severity of vasospastic disorders. MATERIAL AND METHODS Data of 102
      patients admitted to our department with vasospastic disorder symptomatology were
      retrospectively collected. Demographic data, symptoms, and blood test results
      were recorded. Patients were divided into 2 groups according to their rewarming
      time, which is determined by the cold stimulation test. Group 1 consisted of
      patients with rewarming time below 20 min and Group 2 consisted of patients with
      rewarming time above 21 min. Demographic data and blood test results were
      compared between groups. Results were analyzed with the SPSS for Mac 20.0 package
      program. RESULTS There was no statistically significant difference between the
      groups in demographic variables and symptomatology. In Group 2, mean platelet
      volume (MPV) and platelet distribution width (PDW) were higher than in Group 1,
      which was statistically significant (8.87 +/- 0.74 vs. 8.38 +/- 0.78, p=0.001 and
      15.91 +/- 1.92 vs. 14.7 +/- 1.99, p=0.002, respectively). Similar to MPV and PDW,
      lymphocyte count was also higher in Group 2 than in Group 1 (2.28 +/- 0.65 vs.
      1.90 +/- 0.68, p=0.002). CONCLUSIONS Diagnosis and grading the severity of VD is
      challenging, but it can be supported by the presence of increased PDW, MPV, and
      lymphocyte count.

PMID- 25872024
TI  - Quantitative anatomical analysis of facial expression using a 3D motion capture
      system: Application to cosmetic surgery and facial recognition technology.
AB  - The topography of the facial muscles differs between males and females and among
      individuals of the same gender. To explain the unique expressions that people can
      make, it is important to define the shapes of the muscle, their associations with
      the skin, and their relative functions. Three-dimensional (3D) motion-capture
      analysis, often used to study facial expression, was used in this study to
      identify characteristic skin movements in males and females when they made six
      representative basic expressions. The movements of 44 reflective markers (RMs)
      positioned on anatomical landmarks were measured. Their mean displacement was
      large in males [ranging from 14.31 mm (fear) to 41.15 mm (anger)], and 3.35-4.76
      mm smaller in females [ranging from 9.55 mm (fear) to 37.80 mm (anger)]. The
      percentages of RMs involved in the ten highest mean maximum displacement values
      in making at least one expression were 47.6% in males and 61.9% in females. The
      movements of the RMs were larger in males than females but were more limited.
      Expanding our understanding of facial expression requires morphological studies
      of facial muscles and studies of related complex functionality. Conducting these
      together with quantitative analyses, as in the present study, will yield data
      valuable for medicine, dentistry, and engineering, for example, for surgical
      operations on facial regions, software for predicting changes in facial features
      and expressions after corrective surgery, and the development of face-mimicking
      robots.

PMID- 25872025
TI  - Comparison of kinetics, kinematics, and electromyography during single-leg
      assisted and unassisted cycling.
AB  - To use single-leg cycling training for varying populations, it is important to
      understand whether a counterweight attached to the contralateral crank during
      single-leg cycling drills replicates the effects of the opposite leg in the
      ipsilateral leg. Therefore, we compared single-leg assisted cycling using a
      counterweight on the contralateral crank for joint kinetics, kinematics, and
      lower-limb muscle activation. Fourteen healthy nonathletes performed 2 bilateral
      cycling trials (240 +/- 23 W and 90 +/- 2 rpm) and 2 single-leg trials (120 +/-
      11 W and 90 +/- 2 rpm) for measurements of pedal force, joint kinematics, and
      muscle activation of their right lower limb. For 1 single-leg trial, a custom
      made adaptor was used to attach 10 kg of weight to the contralateral leg. Total
      force applied on the pedal, pedal force effectiveness, the mean joint angles and
      range of motion, mechanical work at the crank, hip, knee, and ankle joints,
      electromyography, pedaling cadence, and right crank mechanical work were
      assessed. Biceps femoris (87%), vastus lateralis (15%), rectus femoris (57%),
      tibialis anterior (57%), and gastrocnemius medialis (12%) activations were larger
      in the single-leg assisted trial compared with the bilateral trial. Lower total
      pedal force (17%) and increased index of effectiveness (16%) also indicate
      mechanical differences in single-leg cycling using a counterweight on the
      contralateral crank than conventional bilateral cycling. Single-leg assisted
      training should be used with caution because of potential differences in muscle
      recruitment and pedaling kinetics compared with bilateral cycling.

PMID- 25872026
TI  - FDG-PET/CT detection of very early breast cancer in women with breast
      microcalcification lesions found in mammography screening.
AB  - INTRODUCTION: To assess the efficacy of positron emission tomography/computed
      tomography with the glucose analogue 2-[(18) F]fluoro-2-deoxy-D-glucose (FDG
      PET/CT) in Taiwanese women with early breast cancer detected by mammography
      screening. METHODS: Dual-time-point imaging of whole-body supine and breast prone
      scans using FDG-PET/CT were performed sequentially in the pre-operative stage.
      RESULTS: A total of 11,849 patients underwent screening mammography, of whom
      1,209 (10.2%) displayed positive results. After further investigation, 54
      patients underwent FDG-PET/CT. Post-operative pathology examinations revealed
      malignancies in 26 lesions, including invasive breast cancer in 11 cases and non
      invasive breast cancer in 15 cases, as well as benign disease in 30 lesions. The
      FDG-PET/CT findings from the whole-body scans were positive for 9 of 11 invasive
      breast cancers (81.8%) and 3 of 15 non-invasive cancers (20%), and they were
      negative for all benign lesions. The sensitivity, specificity, positive
      predictive value (PPV) and negative predictive value (NPV) of FDG-PET/CT with
      whole-body supine imaging were 46.2%, 100%, 100% and 68.2%, respectively. Breast
      prone imaging revealed another patient with ductal carcinoma in situ, increasing
      the sensitivity to 50%. Importantly, positive PET findings were significantly
      correlated with tumour histology (P = 0.006), tumour size (P = 0.039) and Ki-67
      expression (P = 0.011). CONCLUSIONS: FDG-PET/CT with whole-body scanning
      demonstrated high sensitivity to invasive breast cancer, limited sensitivity to
      non-invasive breast cancer, and high specificity for breast cancer. FDG-PET/CT
      might be useful for differentiating tumour invasiveness. However, the good PPV
      but poor NPV do not allow the physician to discard the biopsy.

PMID- 25872028
TI  - Evaluation of cardiac electrophysiological properties in an experimental model of
      right ventricular hypertrophy and failure.
AB  - BACKGROUND: Malignant arrhythmias are a major cause of sudden cardiac death in
      adults with congenital heart disease. We developed a model to serially
      investigate electrophysiological properties in an animal model of right
      ventricular hypertrophy and failure. METHOD: We created models of compensated
      (cHF; n=11) and decompensated (dHF; n=11) right ventricular failure in Wistar
      rats by pulmonary trunk banding. Healthy controls underwent sham operation
      (Control; n=13). Surface electrocardiography was recorded from extremities, and
      inducibility of ventricular tachycardia was evaluated in vivo by programmed
      stimulation. Isolated right ventricular myocardium was analysed for mRNA
      expression of selected genes. RESULTS: Banding caused an increased mRNA
      expression of both connexin 43 and the voltage-gated sodium channel 1.5, as well
      as a prolongation of PQ, QRS and QTc intervals. Ventricular tachycardia was
      induced in the majority of banded animals compared with none in the healthy
      control group. No differences were found between the two degrees of failure in
      neither the electrophysiological parameters nor inducibility. CONCLUSIONS: The
      electrophysiological properties of rat hearts subjected to pulmonary trunk
      banding were significantly changed with increased susceptibility to ventricular
      tachycardia, but no differences were found between compensated and decompensated
      right ventricular failure. Furthermore, we demonstrate that in vivo
      electrophysiological evaluation is a sensitive method to characterise the cardiac
      electric phenotype in an experimental rat model.

PMID- 25872027
TI  - Open versus laparoscopic liver resection for colorectal liver metastases (the
      Oslo-CoMet Study): study protocol for a randomized controlled trial.
AB  - BACKGROUND: Laparoscopic liver resection is used in specialized centers all over
      the world. However, laparoscopic liver resection has never been compared with
      open liver resection in a prospective, randomized trial. METHODS/DESIGN: The Oslo
      CoMet Study is a randomized trial into laparoscopic versus open liver resection
      for the surgical management of hepatic colorectal metastases. The primary outcome
      is 30-day perioperative morbidity. Secondary outcomes include 5-year survival
      (overall, disease-free and recurrence-free), resection margins, recurrence
      pattern, postoperative pain, health-related quality of life, and evaluation of
      the inflammatory response. A cost-utility analysis of replacing open surgery with
      laparoscopic surgery will also be performed. The study includes all resections
      for colorectal liver metastases, except formal hemihepatectomies, resections
      where reconstruction of vessels/bile ducts is necessary and resections that need
      to be combined with ablation. All patients will participate in an enhanced
      recovery after surgery program. A biobank of liver and tumor tissue will be
      established and molecular analysis will be performed. DISCUSSION: After 35 months
      of recruitment, 200 patients have been included in the trial. Molecular and
      immunology data are being analyzed. Results for primary and secondary outcome
      measures will be presented following the conclusion of the study (late 2015). The
      Oslo-CoMet Study will provide the first level 1 evidence on the benefits of
      laparoscopic liver resection for colorectal liver metastases. TRIAL REGISTRATION:
      The trial was registered in ClinicalTrals.gov (NCT01516710) on 19 January 2012.

PMID- 25872029
TI  - Engineering Cellular Resistance to HIV-1 Infection In Vivo Using a Dual
      Therapeutic Lentiviral Vector.
AB  - We described earlier a dual-combination anti-HIV type 1 (HIV-1) lentiviral vector
      (LVsh5/C46) that downregulates CCR5 expression of transduced cells via RNAi and
      inhibits HIV-1 fusion via cell surface expression of cell membrane-anchored C46
      antiviral peptide. This combinatorial approach has two points of inhibition for
      R5-tropic HIV-1 and is also active against X4-tropic HIV-1. Here, we utilize the
      humanized bone marrow, liver, thymus (BLT) mouse model to characterize the in
      vivo efficacy of LVsh5/C46 (Cal-1) vector to engineer cellular resistance to HIV
      1 pathogenesis. Human CD34+ hematopoietic stem/progenitor cells (HSPC) either
      nonmodified or transduced with LVsh5/C46 vector were transplanted to generate
      control and treatment groups, respectively. Control and experimental groups
      displayed similar engraftment and multilineage hematopoietic differentiation that
      included robust CD4+ T-cell development. Splenocytes isolated from the treatment
      group were resistant to both R5- and X4-tropic HIV-1 during ex vivo challenge
      experiments. Treatment group animals challenged with R5-tropic HIV-1 displayed
      significant protection of CD4+ T-cells and reduced viral load within peripheral
      blood and lymphoid tissues up to 14 weeks postinfection. Gene-marking and
      transgene expression were confirmed stable at 26 weeks post-transplantation.
      These data strongly support the use of LVsh5/C46 lentiviral vector in gene and
      cell therapeutic applications for inhibition of HIV-1 infection. 

PMID- 25872031
TI  - Beam wander of partially coherent array beams through non-Kolmogorov turbulence.
AB  - Based on the theory of second moments and non-Kolmogorov spectrum, the beam
      wander theory is extend to non-Kolmogorov turbulence, the general analytical
      expression of beam wander in non-Kolmogorov turbulence is derived. Beam wander
      depends on the non-Kolmogorov turbulence parameters and the initial second
      moments of the laser beam at the input plane. Taking the Gaussian Schell model
      array beams as an example, the effects of the generalized exponent parameter,
      inner scale, and outer scale of non-Kolmogorov turbulence and the beam separation
      distance, beam number, and coherence degree on the beam wander are studied in
      detail. It has been shown that the beam wander varies non-monotonically with
      increasing generalized exponent parameter of the turbulence. Furthermore, it
      increases as the inner scale decreases or outer scale increases, and decreases as
      the beam separation distance and beam number increase and the coherence of the
      beam becomes weaker. Our results also indicate that the beam wander could be
      reduced by adjusting the beam parameters appropriately. 

PMID- 25872030
TI  - Targeted metagenomics: finding rare tryptophan dimer natural products in the
      environment.
AB  - Natural product discovery from environmental genomes (metagenomics) has largely
      been limited to the screening of existing environmental DNA (eDNA) libraries.
      Here, we have coupled a chemical-biogeographic survey of chromopyrrolic acid
      synthase (CPAS) gene diversity with targeted eDNA library production to more
      efficiently access rare tryptophan dimer (TD) biosynthetic gene clusters. A
      combination of traditional and synthetic biology-based heterologous expression
      efforts using eDNA-derived gene clusters led to the production of hydroxysporine
      (1) and reductasporine (2), two bioactive TDs. As suggested by our phylogenetic
      analysis of CPAS genes, identified in our survey of crude eDNA extracts,
      reductasporine (2) contains an unprecedented TD core structure: a pyrrolinium
      indolocarbazole core that is likely key to its unusual bioactivity profile. This
      work demonstrates the potential for the discovery of structurally rare and
      biologically interesting natural products using targeted metagenomics, where
      environmental samples are prescreened to identify the most phylogenetically
      unique gene sequences and molecules associated with these genes are accessed
      through targeted metagenomic library construction and heterologous expression. 

PMID- 25872032
TI  - Single-shot speckle reduction in numerical reconstruction of digitally recorded
      holograms.
AB  - A single-shot method to reduce the speckle noise in the numerical reconstructions
      of electronically recorded holograms is presented. A recorded hologram with the
      dimensions N*M is split into S=T*T sub-holograms. The uncorrelated superposition
      of the individually reconstructed sub-holograms leads to an image with the
      speckle noise reduced proportionally to the 1/S law. The experimental results are
      presented to support the proposed methodology. 

PMID- 25872033
TI  - 260-megahertz, megawatt-level thin-disk oscillator.
AB  - A Kerr-lens mode-locked (KLM) Yb:YAG thin-disk oscillator delivering 215-fs
      pulses with 75-W average power and 1.4-MW peak power at a repetition rate of 260
      MHz is presented. Self-starting KLM is demonstrated at an output power of 68 W.
      This is the highest repetition rate of any mode-locked thin-disk oscillators so
      far. Concepts for scaling the repetition rate up to 1 GHz are discussed. 

PMID- 25872034
TI  - Distributed MIMO chaotic radar based on wavelength-division multiplexing
      technology.
AB  - A distributed multiple-input multiple-output chaotic radar based on wavelength
      division multiplexing technology (WDM) is proposed and demonstrated. The wideband
      quasi-orthogonal chaotic signals generated by different optoelectronic
      oscillators (OEOs) are emitted by separated antennas to gain spatial diversity
      against the fluctuation of a target's radar cross section and enhance the
      detection capability. The received signals collected by the receive antennas and
      the reference signals from the OEOs are delivered to the central station for
      joint processing by exploiting WDM technology. The centralized signal processing
      avoids precise time synchronization of the distributed system and greatly
      simplifies the remote units, which improves the localization accuracy of the
      entire system. A proof-of-concept experiment for two-dimensional localization of
      a metal target is demonstrated. The maximum position error is less than 6.5 cm. 

PMID- 25872035
TI  - Discrete plasmonic Talbot effect in finite metal waveguide arrays.
AB  - We introduce supermode theory into the propagation of surface plasmon polaritons
      (SPPs) in nanoscale metal waveguide arrays (MWGAs). The SPP supermodes in finite
      MWGAs are analyzed and the coefficient of excited supermodes can be determined
      quantitatively. The field intensity distributions in finite MWGAs can be
      explained by the superposition of the excited SPP supermodes. The discrete
      plasmonic Talbot effect in a finite MWGA is achieved successfully by adjusting
      different intensity for each input field. We also find that the period condition
      of the input fields in MWGAs is not the same with conventional dielectric
      waveguides. The theory is verified by the finite difference time-domain (FDTD)
      method. 

PMID- 25872036
TI  - On the dual-cone nature of the conical refraction phenomenon.
AB  - In conical refraction (CR), a focused Gaussian input beam passing through a
      biaxial crystal and parallel to one of the optic axes is transformed into a pair
      of concentric bright rings split by a dark (Poggendorff) ring at the focal plane.
      Here, we show the generation of a CR transverse pattern that does not present the
      Poggendorff fine splitting at the focal plane, i.e., it forms a single light
      ring. This light ring is generated from a nonhomogeneously polarized input light
      beam obtained by using a spatially inhomogeneous polarizer that mimics the
      characteristic CR polarization distribution. This polarizer allows modulating the
      relative intensity between the two CR light cones in accordance with the recently
      proposed dual-cone model of the CR phenomenon. We show that the absence of
      interfering rings at the focal plane is caused by the selection of one of the two
      CR cones. 

PMID- 25872037
TI  - Micro-patterned photo-aligned ferroelectric liquid crystal Fresnel zone lens.
AB  - In this Letter, we disclose a fast switchable Fresnel zone lens (FZL) by
      confining the ferroelectric liquid crystals (FLCs) in multiple microscopically
      defined photo-aligned alignment domains. The photo-alignment (PA) offers good
      control on the anchoring energy (W) by mean of irradiation doses (ID) and thus
      excellent alignment for FLCs. Two operational modes of the FLCFZL, i.e.,
      FOCUS/OFF and FOCUS/DEFOCUS, were demonstrated. The proposed diffracting element
      provides fast response time, high diffraction efficiency (eta), with saturated
      electro-optical (EO) operations up to high frequency (~2  kHz). Thus, the
      proposed FLCFZLs with simple fabrication open several opportunities to improve
      the quality of existing devices and to find new applications. 

PMID- 25872038
TI  - Adsorption of cationic organic dyes in suspended-core fibers.
AB  - We report on the absorption measurements of the liquid-filled pure-silica
      microstructured optical fibers. The measurements concentrate on spectroscopic
      analysis of the water solutions of a cationic dye, oxazine 725 perchlorate which,
      when filling the fiber, demonstrates much stronger absorption signals than
      observed in bulk with regular cuvettes. The effect is also seen in another
      cationic dye, but not in anionic dyes. Our investigations reveal that the effect
      originates from the adsorption of the dye molecules on the fiber inner walls.
      This effect also significantly enhances the sensitivity of spectroscopic
      measurements enabling the detection of molecules at very low concentrations. In
      particular, the detection of a 1 nM concentration of oxazine 725 perchlorate was
      demonstrated. 

PMID- 25872039
TI  - Tunable deep-subwavelength superscattering using graphene monolayers.
AB  - In this Letter, we theoretically propose for the first time that graphene
      monolayers can be used for superscatterer designs. We show that the scattering
      cross-section of the bare deep-subwavelength dielectric cylinder is markedly
      enhanced by six orders of magnitude due to the excitation of the first-order
      resonance of graphene plamons. By utilizing the tunability of the plasmonic
      resonance through tuning graphene's chemical potential, the graphene
      superscatterer works in a wide range of frequencies from several terahertz to
      tens of terahertz. 

PMID- 25872040
TI  - x-y curvature wavefront sensor.
AB  - In this Letter, we propose a new curvature wavefront sensor based on the
      principles of optical differentiation. The theoretically modeled setup consists
      of a diffractive optical mask placed at the intermediate plane of a classical two
      lens coherent optical processor. The resulting image is composed of a number of
      local derivatives of the entrance pupil function whose proper combination
      provides the wavefront curvature. In contrast to the common radial curvature
      sensors, this one is able to provide the x and y wavefront curvature maps
      simultaneously. The sensor offers other additional advantages like having high
      spatial resolution, adjustable dynamic range, and not being sensitive to
      misalignment. 

PMID- 25872041
TI  - Enhancing Eu(3+) magnetic dipole emission by resonant plasmonic nanostructures.
AB  - We demonstrate the enhancement of magnetic dipole spontaneous emission from
      Eu<sup>3+</sup> ions by an engineered plasmonic nanostructure that controls the
      electromagnetic environment of the emitter. Using an optical microscope setup, an
      enhancement in the intensity of the Eu<sup>3+</sup> magnetic dipole emission was
      observed for emitters located in close vicinity to a gold nanohole array designed
      to support plasmonic resonances overlapping with the emission spectrum of the
      ions. 

PMID- 25872042
TI  - Six mode selective fiber optic spatial multiplexer.
AB  - Low-loss all-fiber photonic lantern (PL) mode multiplexers (MUXs) capable of
      selectively exciting the first six fiber modes of a multimode fiber
      (LP<sub>01</sub>, LP<sub>11a</sub>, LP<sub>11b</sub>, LP<sub>21a</sub>,
      LP<sub>21b</sub>, and LP<sub>02</sub>) are demonstrated. Fabrication of the
      spatial mode multiplexers was successfully achieved employing a combination of
      either six step or six graded index fibers of four different core sizes.
      Insertion losses of 0.2-0.3 dB and mode purities above 9 dB are achieved.
      Moreover, it is demonstrated that the use of graded index fibers in a PL eases
      the length requirements of the adiabatic tapered transition and could enable
      scaling to large numbers. 

PMID- 25872043
TI  - Focusing through turbid media by polarization modulation.
AB  - We demonstrate that polarization modulation of an illumination beam can
      effectively control the spatial profile of the light transmitted through turbid
      media. Since the transmitted electric fields are completely mingled in turbid
      media, polarization states of an illumination beam can be used effectively to
      control the propagation of light through turbid media. Numerical simulations were
      performed which agree with experimental results obtained using a commercial in
      plane switching liquid crystal display for modulating the input polarization
      states. 

PMID- 25872044
TI  - All-in-focus image reconstruction under severe defocus.
AB  - Limited depth-of-focus is a problem in many fields of optics, e.g., microscopy
      and macro-photography. We propose a new physically based method with a space
      variant point spread function (PSF) to accomplish all-in-focus reconstruction
      (image fusion) from a multi-focus image sequence in order to extend the depth-of
      field. The proposed method works well under strong defocus conditions for color
      image stacks of arbitrary length. Experimental results are provided to
      demonstrate that our method outperforms state-of-the-art image fusion algorithms
      for strong defocus on both synthetic as well as real data images. 

PMID- 25872045
TI  - Efficient generation of below-threshold harmonics for high-fidelity multi-photon
      physics in the VUV spectral range.
AB  - We demonstrate the generation of microjoule level, sub-20-fs, Ti:Sa fifth
      harmonic pulses utilizing a loose-focusing geometry in a long Ar gas cell. The
      VUV pulses centered at 161.8 nm reach pulse energies of 1.1 MUJ per pulse, while
      the corresponding pulse duration is measured with a second-order, fringe-resolved
      autocorrelation scheme to be 18+/-1  fs. Nonresonant, two-photon ionization of Kr
      and three-photon ionization of Ne verify the fifth-harmonic pulse high-intensity
      content and indicate the feasibility of multi-photon VUV pump-VUV probe studies
      of ultrafast atomic and molecular dynamics. 

PMID- 25872046
TI  - Optical vector network analyzer with improved accuracy based on polarization
      modulation and polarization pulling.
AB  - We report a novel optical vector network analyzer (OVNA) with improved accuracy
      based on polarization modulation and stimulated Brillouin scattering (SBS)
      assisted polarization pulling. The beating between adjacent higher-order optical
      sidebands which are generated because of the nonlinearity of an electro-optic
      modulator (EOM) introduces considerable error to the OVNA. In our scheme, the
      measurement error is significantly reduced by removing the even-order optical
      sidebands using polarization discrimination. The proposed approach is
      theoretically analyzed and experimentally verified. The experimental results show
      that the accuracy of the OVNA is greatly improved compared to a conventional
      OVNA. 

PMID- 25872047
TI  - Rapid super-resolution line-scanning microscopy through virtually structured
      detection.
AB  - Virtually structured detection (VSD) has been demonstrated to break the
      diffraction limit in scanning laser microscopy (SLM). VSD provides an easy, low
      cost, and phase-artifact-free strategy to achieve super-resolution imaging.
      However, practical application of this method is challenging due to a limited
      image acquisition speed. We report here the combination of VSD and line-scanning
      microscopy (LSM) to improve the image acquisition speed. A motorized dove prism
      was used to achieve automatic control of four-angle (i.e., 0 degrees , 45 degrees
      , 90 degrees , and 135 degrees ) scanning, thus ensuring isotropic resolution
      improvement. Both an optical resolution target and a living frog eyecup were used
      to verify resolution enhancement. 

PMID- 25872048
TI  - Flash-imprinting of intense femtosecond surface plasmons for advanced nanoantenna
      fabrication.
AB  - In this work, we demonstrate an all-laser method of fabrication of optical
      nanoantennas (ONAs) with an additional coupling/focusing diffractive element.
      This method is based on double-shot femtosecond laser nanoablation of a thin
      supported metallic film, inducing a sequence of electrodynamic (surface plasmon
      polariton [SPP] excitation and interference), thermal (melting, ablation and
      ultrafast cooling), and hydrodynamic processes. In particular, the thermal and
      hydrodynamic processes are important for ONA formation after the first laser
      shot, while second spatially shifted laser shot via an induced SPP wave results
      in a radial surface grating near the nanoantenna. Such gratings provide efficient
      coupling between incident laser radiation and SPP waves, thus significantly
      improving the ONA efficiency. 

PMID- 25872049
TI  - Mode-locked all-fiber laser producing radially polarized rectangular pulses.
AB  - We propose and demonstrate a radially polarized mode-locked fiber laser through
      the use of a figure-8 cavity in combination with cascade fiber Bragg gratings
      (FBGs). The mode-locked laser emits rectangular pulses with width tunable from
      2.8 to 23 ns under an increasing pump power at 1056.3 nm with 0.2-nm 30-dB
      linewidth. A polarization purity as high as 96% for the output transverse mode
      has been achieved simultaneously. 

PMID- 25872050
TI  - Conditions for stronger field enhancement of semiconductor bowtie nanoantennas.
AB  - A semiconductor bowtie nanoantenna acts as a high-quality cavity because a
      strongly enhanced field with a narrow spectral width appears at a nanogap region
      owing to exciton resonance. We theoretically investigate suitable antenna
      structures to obtain a strong field enhancement, and the following conditions are
      found: (i) the antenna structure is long in the direction of light polarization,
      and (ii) the tip structure near the nanogap is blunt. Condition (ii) is opposite
      to that for a metallic bowtie nanoantenna because the exciton wave function is
      distributed to avoid a narrow area near the sharp tip. These conditions are
      expected to be guidelines for designing efficient semiconductor nanoantennas for
      various applications. 

PMID- 25872051
TI  - Mid-infrared lasing from Ho(3+) in bulk InF(3) glass.
AB  - We report on an Ho<sup>3+</sup>:InF<sub>3</sub> glass laser pumped by a
      Cr<sup>3+</sup>:LiSAF laser emitting at 889 nm. Ho<sup>3+</sup>:InF<sub>3</sub>
      glass is a promising material for direct mid-infrared lasers around 4 MUm. To
      evaluate the performances of this new material, we compared it to an
      Ho<sup>3+</sup>:BYF crystalline laser pumped by the same source. At 650 mJ pump
      energy, 7.2 mJ (46 mJ) was obtained with Ho<sup>3+</sup>:InF<sub>3</sub>
      (Ho<sup>3+</sup>:BYF), respectively. This is, to the best of our knowledge, the
      first reported laser activity in this type of glass. 

PMID- 25872052
TI  - Structured film for compensation of anthropogenic radiative forcing.
AB  - A possible solution for the global warming problem consists of scattering the
      solar radiation by a cloud of screens, placed near the inner Lagrange point (L1),
      between the sun and the earth. The thin film material for such a screen should
      have a high longevity in space environment, low areal density, high on-axis
      scattering, very low integral reflectivity over the whole solar spectrum, and
      good handling properties such as foldability and robustness. We report on
      experimental fabrication of free-standing robust nitride films satisfying to most
      optical and mechanical requirements for such a screen. 

PMID- 25872053
TI  - Sensing earth's rotation with a helium-neon ring laser operating at 1.15  MUm.
AB  - We report on the operation of a 2.56  m<sup>2</sup> helium-neon based ring laser
      interferometer at a wavelength of 1.152276 MUm using crystalline coated
      intracavity supermirrors. This work represents the first implementation of
      crystalline coatings in an active laser system and expands the core application
      area of these low-thermal-noise cavity end mirrors to inertial sensing systems.
      Stable gyroscopic behavior can only be obtained with the addition of helium to
      the gain medium as this quenches the 1.152502 MUm (2s<sub>4</sub>
      >2p<sub>7</sub>) transition of the neon doublet which otherwise gives rise to
      mode competition. For the first time at this wavelength, the ring laser is
      observed to readily unlock on the bias provided by the earth's rotation alone,
      yielding a Sagnac frequency of approximately 59 Hz. 

PMID- 25872054
TI  - Can a sphere scatter light producing rectangular intensity patterns?
AB  - Random stationary media of a spherical shape, having well-chosen refractive index
      correlation properties are shown to scatter light to far fields with intensity
      patterns that possess rectangular symmetry. The analysis is valid under the first
      Born approximation. 

PMID- 25872055
TI  - Absolute near-infrared refractometry with a calibrated tilted fiber Bragg
      grating.
AB  - The absolute refractive indices (RIs) of water and other liquids are determined
      with an uncertainty of +/-0.001 at near-infrared wavelengths by using the tilted
      fiber Bragg grating (TFBG) cladding mode resonances of a standard single-mode
      fiber to measure the critical angle for total internal reflection at the
      interface between the fiber and its surroundings. The necessary condition to
      obtain absolute RIs (instead of measuring RI changes) is a thorough
      characterization of the dispersion of the core mode effective index of the TFBG
      across the full range of its cladding mode resonance spectrum. This technique is
      shown to be competitive with the best available measurements of the RIs of water
      and NaCl solutions at wavelengths in the vicinity of 1550 nm. 

PMID- 25872056
TI  - On the properties of circular beams: normalization, Laguerre-Gauss expansion, and
      free-space divergence.
AB  - Circular beams were introduced as a very general solution to the paraxial wave
      equation carrying orbital angular momentum. Here, we study their properties by
      looking at their normalization and their expansion in terms of Laguerre-Gauss
      modes. We also study their far-field divergence and, for particular cases of the
      beam parameters, their possible experimental generation. 

PMID- 25872058
TI  - Optical frequency domain reflectometry at maximum update rate using I/Q
      detection.
AB  - We introduce a new optical frequency domain reflectometry (OFDR) system and
      processing method that utilize negative beat frequencies for the first time. The
      new approach enables efficient use of the available system bandwidth and
      facilitates distributed sensing with the maximum allowable update rate for a
      given fiber length. This is achieved by using a coherent optical-communications
      type receiver that detects both the in-phase (I) and quadrature (Q) components of
      the backscatter field. The I and Q components are digitally combined to produce a
      complex backscatter signal whose Fourier transform is not necessarily symmetric.
      Judicious processing of the complex backscatter signal maps the reflection
      profile of one half of the sensing fiber to positive beat-frequencies and the
      profile of the other half to negative beat-frequencies. The new approach was
      tested via comprehensive computer simulations and experiment. 

PMID- 25872057
TI  - Bone assessment via thermal photo-acoustic measurements.
AB  - The feasibility of an innovative biomedical diagnostic technique, thermal photo
      acoustic (TPA) measurement, for non-ionizing and non-invasive assessment of bone
      health is investigated. Unlike conventional photo-acoustic PA methods that are
      mostly focused on the measurement of absolute signal intensity, TPA targets the
      change in PA signal intensity as a function of the sample temperature, i.e., the
      temperature-dependent Grueneisen parameter that is closely relevant to the
      chemical and molecular properties in the sample. Based on the differentiation
      measurement, the results from TPA technique are less susceptible to the
      variations associated with sample and system, and could be quantified with
      improved accurately. Due to the fact that the PA signal intensity from organic
      components such as blood changes faster than that from non-organic mineral under
      the same modulation of temperature, TPA measurement is able to objectively
      evaluate bone mineral density (BMD) and its loss as a result of osteoporosis. In
      an experiment on well-established rat models of bone loss and preservation, PA
      measurements of rat tibia bones were conducted over a temperature range from 37
      degrees C to 44 degrees C. The slope of PA signal intensity verses temperature
      was quantified for each specimen. The comparison among three groups of specimens
      with different BMD shows that bones with lower BMD have higher slopes,
      demonstrating the potential of the proposed TPA technique in future clinical
      management of osteoporosis. 

PMID- 25872059
TI  - Q-plates as higher order polarization controllers for orbital angular momentum
      modes of fiber.
AB  - We demonstrate that a |q|=1/2 plate, in conjunction with appropriate polarization
      optics, can selectively and switchably excite all linear combinations of the
      first radial mode order |l|=1 orbital angular momentum (OAM) fiber modes. This
      enables full mapping of free-space polarization states onto fiber vector modes,
      including the radially (TM) and azimuthally polarized (TE) modes. The setup
      requires few optical components and can yield mode purities as high as ~30  dB.
      Additionally, just as a conventional fiber polarization controller creates
      arbitrary elliptical polarization states to counteract fiber birefringence and
      yield desired polarizations at the output of a single-mode fiber, q-plates
      disentangle degenerate state mixing effects between fiber OAM states to yield
      pure states, even after long-length fiber propagation. We thus demonstrate the
      ability to switch dynamically, potentially at ~GHz rates, between OAM modes, or
      create desired linear combinations of them. We envision applications in fiber
      based lasers employing vector or OAM mode outputs, as well as communications
      networking schemes exploiting spatial modes for higher dimensional encoding. 

PMID- 25872060
TI  - Ultra-compact TE-pass polarizer with graphene multilayer embedded in a silicon
      slot waveguide.
AB  - A novel silicon slot waveguide TE-pass polarizer with graphene multilayer
      embedded in the slot is proposed and demonstrated by utilization of the fact that
      the variation of the modal characteristics for the TM mode is more than that for
      the TE mode. The designed polarizer is shown to have the ability to significantly
      suppress the transmission of the TM mode, while well guiding the TE mode. We
      numerically demonstrate a 7-MUm-long polarizer has an ultra-high insertion loss
      of 31.5 dB for the TM mode and as little insertion loss as 0.2 dB for the TE mode
      at 1.55 MUm. The presented polarizer offers the performance merits including high
      extinction ratio, ultra-low insertion loss, ultra-compactness, and easy
      integration with silicon slot waveguides without using any taper. 

PMID- 25872061
TI  - Combined "dual" absorption and fluorescence smartphone spectrometers.
AB  - A combined "dual" absorption and fluorescence smartphone spectrometer is
      demonstrated. The optical sources used in the system are the white flash LED of
      the smartphone and an orthogonally positioned and interchangeable UV
      (lambda<sub>ex</sub>=370  nm) and blue (lambda<sub>ex</sub>=450  nm) LED. The
      dispersive element is a low-cost, nano-imprinted diffraction grating coated with
      Au. Detection over a 300 nm span with 0.42 nm/pixel resolution was carried out
      with the camera CMOS chip. By integrating the blue and UV excitation sources into
      the white LED circuitry, the entire system is self-contained within a 3D printed
      case and powered from the smartphone battery; the design can be scaled to add
      further excitation sources. Using a customized app, acquisition of absorption and
      fluorescence spectra are demonstrated using a blue-absorbing and green-emitting
      pH-sensitive amino-naphthalimide-based fluorescent probe and a UV-absorbing and
      blue-emitting Zn<sup>2+</sup>-sensitive fluoro-ionophore. 

PMID- 25872062
TI  - Large-mode-area hybrid photonic crystal fiber amplifier at 1178  nm.
AB  - Amplification of 1178 nm light is demonstrated in a large-mode-area single-mode
      ytterbium-doped hybrid photonic crystal fiber, relying on distributed spectral
      filtering of spontaneous emission at shorter wavelengths. An output power of 53 W
      is achieved with 29 dB suppression of parasitic lasing. Further power scaling is
      limited by parasitic lasing. 

PMID- 25872063
TI  - Controllable near-field intensity and spot size of hybrid terahertz metamaterial.
AB  - We report controllable near fields around split-ring resonator (SRR) gaps of an
      active terahertz metamaterial. As extension of parallel-plate capacitors,
      patterned VO<sub>2</sub> is integrated into the metallic SRRs to manipulate the
      near-field intensity and hot spot size through its metal-insulator transition.
      This design enhances the device reliability by preventing VO<sub>2</sub>
      dielectric breakdown at a strongly enhanced near field. The near-field intensity
      and spot size are tunable in broad ranges, and the device is demonstrated to be
      capable of compensating resonant frequency drift arisen from different
      interactions due to near-field coupling. It provides an effective method to
      actively manipulate the light-matter interaction through the strongly enhanced
      and tunable near fields. 

PMID- 25872064
TI  - New experimental method for lidar overlap factor using a CCD side-scatter
      technique.
AB  - In theory, lidar overlap factor can be derived from the difference between the
      particle backscatter coefficient retrieved from lidar elastic signal without
      overlap correction and the actual particle backscatter coefficient, which can be
      obtained by other measured techniques. The side-scatter technique using a CCD
      camera is testified to be a powerful tool to detect the particle backscatter
      coefficient in near ground layer during night time. A new experiment approach to
      determine the overlap factor for vertically pointing lidar is presented in this
      study, which can be applied to Mie lidars. The effect of overlap factor on Mie
      lidar is corrected by an iteration algorithm combining the retrieved particle
      backscatter coefficient using CCD side-scatter method and Fernald method. This
      method has been successfully applied to Mie lidar measurements during a routine
      campaign, and the comparison of experimental results in different atmosphere
      conditions demonstrated that this method is available in practice. 

PMID- 25872065
TI  - Laser oscillation in Yb:YAG waveguide beam-splitters with variable splitting
      ratio.
AB  - In this Letter, we report on laser emission from Yb:YAG beam-splitters fabricated
      by direct femtosecond-laser inscription. These devices consist of two adjacent
      mirrored s-curved waveguides merged into a section allowing for multi-mode
      interference (MMI) and a straight waveguide. Nine-millimeter-long one-to-two beam
      splitters with radii of curvature between 10 and 80 mm have been fabricated
      resulting in separations between the two arms of up to 0.65 mm. Due to the MMI
      section, the splitting ratio was variable by slightly changing the incoupling
      conditions. Maximum laser output powers of 2.29 W and slope efficiencies of 52%
      were achieved with the best beam-splitter waveguide laser. For all radii of
      curvature exceeding 10 mm, similar efficiencies were demonstrated. 

PMID- 25872066
TI  - Single-mode master-oscillator power amplifier at 647  nm with more than 500 mW
      output power.
AB  - Using an AlGaInP-based truncated tapered power amplifier, it was possible to
      boost the output power of a 647-nm distributed Bragg reflector laser from 50 mW
      to more than 500 mW. The light source has the potential to replace bulky Kr ion
      lasers still in use at this wavelength. 

PMID- 25872067
TI  - Wavelength interrogation of fiber Bragg grating sensors based on crossed optical
      Gaussian filters.
AB  - Conventional intensity-modulated measurements require to be operated in linear
      range of filter or interferometric response to ensure a linear detection. Here,
      we present a wavelength interrogation system for fiber Bragg grating sensors
      where the linear transition is achieved with crossed Gaussian transmissions. This
      unique filtering characteristic makes the responses of the two branch detections
      follow Gaussian functions with the same parameters except for a delay. The
      substraction of these two delayed Gaussian responses (in dB) ultimately leads to
      a linear behavior, which is exploited for the sensor wavelength determination.
      Beside its flexibility and inherently power insensitivity, the proposal also
      shows a potential of a much wider operational range. Interrogation of a strain
      tuned grating was accomplished, with a wide sensitivity tuning range from 2.56 to
      8.7 dB/nm achieved. 

PMID- 25872068
TI  - Shaping optical beams with non-integer orbital-angular momentum: a generalized
      differential operator approach.
AB  - We introduce an analytical procedure to construct an optical beam with an
      arbitrary value of orbital-angular momentum (OAM) by keeping the flexibility of
      shaping its transverse intensity distribution without changing its OAM. We apply
      the general theory of fractional differential operators in Fourier domain to
      derive general expressions for the OAM content in the beam and find the relevant
      parameters that determine its OAM value and those that can be freely modified
      without affecting it. 

PMID- 25872069
TI  - Controlling attosecond angular streaking with second harmonic radiation.
AB  - High harmonic generation, which produces a coherent burst of radiation every half
      cycle of the driving field, has been combined with ultrafast wavefront rotation
      to create a series of spatially separated attosecond pulses, called the
      attosecond lighthouse. By adding a coherent second harmonic beam with
      polarization parallel to the fundamental, we decrease the generating frequency
      from twice per optical cycle to once. The increased temporal separation increases
      the pulse contrast. By scanning the carrier envelope phase, we see that the
      signal is 2pi periodic. 

PMID- 25872070
TI  - Diffraction-induced instability of coupled dark solitary waves.
AB  - We report on a novel instability arising from the propagation of coupled dark
      solitary beams governed by coupled defocusing nonlinear Schrodinger equations.
      Considering dark notches on backgrounds with different wavelengths, hence
      different diffraction coefficients, we find that the vector dark soliton solution
      is unstable to radiation modes. Using perturbation theory and numerical
      integration, we demonstrate that the component undergoing stronger diffraction
      radiates away, leaving a single dark soliton in the other mode/wavelength. 

PMID- 25872071
TI  - Generating polarization vortices by using helical beams and a Twyman Green
      interferometer.
AB  - A stable interferometric arrangement consisting of a polarizing beam splitter, a
      reflector, and a right-angle prism is designed to transform helical beams into
      polarization vortices. The computer-generated holograms are loaded on the liquid
      crystal spatial light modulator (LC-SLM) in order to generate different helical
      beams. Then the helical beams are transformed into polarization vortices with
      different kinds of intensity distribution successfully. 

PMID- 25872073
TI  - Intensity dynamics and statistical properties of random distributed feedback
      fiber laser.
AB  - We present first experimental investigation of fast-intensity dynamics of random
      distributed feedback (DFB) fiber lasers. We found that the laser dynamics are
      stochastic on a short time scale and exhibit pronounced fluctuations including
      generation of extreme events. We also experimentally characterize statistical
      properties of radiation of random DFB fiber lasers. We found that statistical
      properties deviate from Gaussian and depend on the pump power. 

PMID- 25872072
TI  - 4D optical coherence tomography-based micro-angiography achieved by 1.6-MHz FDML
      swept source.
AB  - We demonstrate the use of an ultra-high-speed swept-source optical coherence
      tomography (OCT) to achieve optical micro-angiography (OMAG) of microcirculatory
      tissue beds in vivo. The system is based on a 1310-nm Fourier domain mode-locking
      (FDML) laser with 1.6-MHz A-line rate, providing a frame rate of 3.415 KHz, an
      axial resolution of ~10  MUm and signal to noise ratio of 102 dB. Motion from
      blood flow causes change in OCT signals between consecutive B-frames acquired at
      the same location. Intensity-based inter-frame subtraction algorithm is applied
      to extract blood flow from tissue background without any motion correction. We
      demonstrate the capability of this 1.6-MHz OCT system for 4D OMAG of in vivo
      tissue at a volume rate of 4.7 volumes/s (volume size: 512*200*720 voxels). 

PMID- 25872074
TI  - Multi-stability and polariton solitons in microcavity wires.
AB  - Nonlinear polaritons in microcavity wires are demonstrated to exhibit multi
      stable behavior and rich dynamics, including filamentation and soliton formation.
      We find that the multi-stability originates from co-existence of different
      transverse cavity modes. Modulational stability and conditions for multi-mode
      polariton solitons are studied. Soliton propagation in tilted, relative to the
      pump momentum, microcavity wires is demonstrated, and a critical tilt angle for
      the soliton propagation is found. 

PMID- 25872075
TI  - Temperature-insensitivity gas pressure sensor based on inflated long period fiber
      grating inscribed in photonic crystal fiber.
AB  - We demonstrated an inflated long period fiber grating (I-LPFG) inscribed in a
      pure-silica photonic crystal fiber (PCF) for high-sensitivity gas pressure
      sensing applications. The I-LPFG was inscribed by use of the pressure-assisted
      CO<sub>2</sub> laser beam-scanning technique to inflate periodically air holes of
      a PCF along the fiber axis. Such an I-LPFG with periodic inflations exhibits a
      very high gas pressure sensitivity of 1.68 nm/MPa, which is one order of
      magnitude higher than that, i.e., 0.12 nm/Mpa, of the LPFG without periodic
      inflations. Moreover, the I-LPFG has a very low temperature sensitivity of 3.1
      pm/ degrees C due to the pure silica material in the PCF so that the pressure
      measurement error, resulting from the cross-sensitivity between temperature and
      gas pressure, is less than 1.8 Kpa/ degrees C in the case of no temperature
      compensation. So the I-LPFG could be used to develop a promising gas pressure
      sensor, and the achieved pressure measurement range is up to 10 MPa. 

PMID- 25872076
TI  - Monolithic 16-wavelength selector based on a chain of passband-flattened cyclic
      AWGs and optical switches.
AB  - An InP monolithically integrated wavelength selector based on combinations of
      integrated AWGs and SOAs selects one out of up to 16 input channels. Loss
      compensated, error-free WDM channel selection operation with <2.3  dB penalties
      is reported, with an OSNR of up to 32.5  dB/0.1  nm. 

PMID- 25872077
TI  - Optical driven electromechanical transistor based on tunneling effect.
AB  - A new electromechanical transistor based on an optical driven vibrational ring
      structure has been postulated. In the device, optical power excites the ring
      structure to vibrate, which acts as the shuttle transporting electrons from one
      electrode to the other forming the transistor. The electrical current of the
      transistor is adjusted by the optical power. Coupled opto-electro-mechanical
      simulation has been performed. It is shown from the dynamic analysis that the
      stable working range of the transistor is much wider than that of the optical
      wave inside the cavity, i.e., the optical resonance enters nonperiodic states
      while the mechanical vibration of the ring is still periodic. 

PMID- 25872078
TI  - Super-resolution using Barker-based array projected via spatial light modulator.
AB  - The use of a two-dimensional Barker-based array in the conventional time
      multiplexing super-resolution (TMSR) technique was recently presented [Opt.
      Lett.40, 163-165 (2015)OPLEDP0146-959210.1364/OL.40.000163]. It enables achieving
      a two-dimensional SR image using only a one-dimensional scan, by exploiting its
      unique auto-correlation property. In this Letter, we refine the method using a
      mismatched array for the decoding process. The cross-correlation between the
      Barker-based array and the mismatched array has a perfect peak-to-sidelobes
      ratio, making it ideal for the SR process. Also, we propose the projection of
      this array onto the object using a phase-only spatial light modulator. Projecting
      the array eliminates the need for printing it, mechanically shifting it, and
      having a direct contact with the object, which is not feasible in many imaging
      applications. 13 phase masks, which generate shifted Barker-based arrays, were
      designed using a revised Gerchberg-Saxton algorithm. A sequence of 13 low
      resolution images were captured using these phase masks, and were decoded using
      the mismatched arrays, resulting in a high-resolution image. The proposed
      mismatched array and the design process of the phase masks are presented, and the
      method is validated by a laboratory experiment. 

PMID- 25872079
TI  - Ultimate propulsion of wavelength-sized dielectric particles.
AB  - It is shown that a wavelength-sized dielectric particle can form a resonant state
      with the below-cutoff mode of a waveguide even for rather small values of the
      refractive index contrast between the particle and the background. The excitation
      of the resonant state creates the propelling force twice the momentum flow of the
      incident mode, and the particle is reliably trapped at the waveguide center.
      Since neither the particle nor the waveguide possesses individually any resonant
      properties, this operating regime can be applicable for the manipulation of
      particles of various materials, sizes, and shapes. 

PMID- 25872080
TI  - Smooth bridge between guided waves and spoof surface plasmon polaritons.
AB  - In this work, we build a smooth bridge between a coaxial waveguide and a
      plasmonic waveguide with subwavelength periodically cylindrical radial grooves,
      to realize high-efficiency mode conversion between conventional guided waves and
      spoof surface plasmon polaritons in broadband. This bridge consists of a flaring
      coaxial waveguide connected with a metal cylindrical wire corrugated with
      subwavelength gradient radial grooves. Experimental results of the transmission
      and reflection coefficients show excellent agreement with the numerical
      simulations. The proposed scheme can be extended readily to other bands and the
      bridge structure can find potential applications in the integration of
      conventional microwave or terahertz devices with plasmonic circuits. 

PMID- 25872081
TI  - Lensless three-dimensional integral imaging using variable and time multiplexed
      pinhole array.
AB  - We present a multivariable coded aperture (MVCA) for lensless three-dimensional
      integral imaging (3D II) systems. The new configuration is based on a time
      multiplexing method using a variable pinholes array design. The system provides
      higher resolution 3D images with improved light intensity and signal to noise
      ratio as compared to single-pinhole system. The MVCA 3D II system configuration
      can be designed to achieve high light intensity for practical use as
      microlenslets arrays. This new configuration preserves the advantages of pinhole
      optics while solving the resolution limitation problem and the long exposure time
      of such systems. The three-dimensional images are obtained with improved
      resolution, signal to noise ratio, and light efficiency. This integral imaging
      lensless system is characterized by large depth of focus, simplicity, and low
      cost. 

PMID- 25872082
TI  - Optical binding in white light.
AB  - We experimentally demonstrate, for the first time, binding of aerosols of various
      sizes and shapes in white light. The optomechancial interaction between particles
      is long range and is in the underdamped regime. Incoherency allows mitigation of
      interference fringes to enable monotonically changing the distance between
      particles from 60 MUm to contact, constituting a parametrically controlled
      testbed for transition studies at new scales. 

PMID- 25872083
TI  - Broadband, unpolarized repumping and clearout light sources for Sr(+) single-ion
      clocks.
AB  - Future transportable optical clocks require compact and reliable light sources.
      Here, broadband, unpolarized repumper and state clearout sources for
      Sr<sup>+</sup> single-ion optical clocks are reported. These turn-key devices
      require no frequency stabilization or external modulators. They are fiber based,
      inexpensive, and compact. Key characteristics for clock operation are presented,
      including optical spectra, induced light shifts, and required extinction ratios.
      Tests with an operating single-ion standard show a clearout efficiency of 100%.
      Compared to a laser-based repumper, the achievable fluorescence rates for ion
      detection are a few tens of percent lower. The resulting ion kinetic temperature
      is 1-1.5 mK, near the Doppler limit of the ion system. Similar repumper light
      sources could be made for Ca<sup>+</sup> (866 nm) and Ba<sup>+</sup> (650 nm)
      using semiconductor gain media. 

PMID- 25872084
TI  - Polarization nonreciprocity suppression of dual-polarization fiber-optic
      gyroscope under temperature variation.
AB  - Polarization nonreciprocity (PN) is one of the most critical factors that
      degrades the performance of interferometric fiber-optic gyroscopes (IFOGs),
      particularly under varying temperature. We present an experimental investigation
      of PN error suppression in a dual-polarization IFOG. Both experimental results
      and theoretical analysis indicate that the PN errors of the two orthogonally
      polarized light waves always have opposite signs that can be effectively
      compensated despite the temperature variation. As a result, the long-term
      stability of the IFOG has been significantly improved. This study is promising
      for reducing the temperature fragility of IFOGs. 

PMID- 25872085
TI  - Cladded self-written multimode step-index waveguides using a one-polymer
      approach.
AB  - Low-loss optical-coupling structures are highly relevant for applications in
      fields as diverse as information and communication technologies, integrated
      circuits, or flexible and highly-functional polymer sensor networks. For this
      suitable and reliable production methods are crucial. Self-written waveguides are
      an interesting solution. In this work, we present a simple and efficient one
      polymer approach for self-written optical connections between light-guiding
      structures such as single-mode and multi-mode optical fibers or waveguides that
      relies on self focusing of the light inside a photopolymerizing mixture. The
      optical connections are produced in a two-step process by writing into monomer
      resin using cw laser light in the blue wavelength range and subsequent UV curing.
      Since only one photopolymerizing resin is required, we reduced the fabrication
      complexity compared to previous approaches to obtain a waveguide embedded in a
      rigid cladding material. We discuss the production method, the results obtained
      as function of relevant process parameters such as writing speed or curing time,
      and evaluate optical properties and coupling efficiencies. 

PMID- 25872086
TI  - Coupled-mode-induced transparency in aerostatically tuned microbubble whispering
      gallery resonators.
AB  - Coupled-mode-induced transparency is realized in a single microbubble whispering
      gallery mode resonator. Using aerostatic tuning, we find that the pressure
      induced shifting rates are different for different radial order modes. A finite
      element simulation considering both the strain and stress effects shows a GHz/bar
      difference, and this is confirmed by experiments. A transparency spectrum is
      obtained when a first-order mode shifts across a higher order mode through
      precise pressure tuning. The resulting lineshapes are fitted with the theory.
      This work lays a foundation for future applications in microbubble sensing. 

PMID- 25872087
TI  - Theory of phonon-modified quantum dot photoluminescence intensity in structured
      photonic reservoirs.
AB  - The spontaneous emission rate of a quantum dot coupled to a structured photonic
      reservoir is determined by the frequency dependence of its local density of
      photon states. Through phonon-dressing, a breakdown of Fermi's golden rule can
      occur for certain photonic structures whose photon decay time becomes comparable
      to the longitudinal acoustic phonon decay times. We present a polaron master
      equation model to calculate the photoluminescence intensity from a coherently
      excited quantum dot coupled to a structured photonic reservoir. We consider
      examples of a semiconductor microcavity and a coupled cavity waveguide, and show
      clear photoluminescence intensity spectral features that contain unique
      signatures of the interplay between phonon and photon bath coupling. 

PMID- 25872088
TI  - Digital resampling diversity sparsity constrained-wavefield reconstruction using
      single-magnitude image.
AB  - Phase retrieval is a well-established method for the recovery of an object wave
      from its magnitude-only measurements, with applications in fields such as
      material science, biology, and astronomy. In order to guarantee a stable and
      global solution for phase retrieval, measurement diversity is frequently used.
      However, this process requires taking several measurements, which hinders some of
      the advantages of phase retrieval compared with interferometric techniques. Here
      we propose a novel diversity framework that we refer to as digital resampling
      diversity. The proposed resampling diversity along with sparsity-constrained
      object reconstruction enables improved object reconstruction from a single
      squared magnitude image, without using object support constraint. We demonstrate
      this framework with simulation and experimental results. 

PMID- 25872089
TI  - Correlations in pulsed resonance fluorescence.
AB  - We investigated the first and second-order correlations of the light scattered
      near-resonantly by a quantum dot under excitation by a frequency comb, i.e., a
      periodically pulsed laser source. In contrast to its monochromatic counterpart,
      the pulsed resonance fluorescence spectrum features a superposition of sidebands
      distributed around a central peak with maximal sideband intensity near the Rabi
      frequency. Distinguishing between the coherently and incoherently scattered light
      reveals pulse-area dependent Rabi oscillations evolving with different phase for
      each component. Our observations, which can be reproduced theoretically, may
      impact schemes for remote entanglement based on pulsed two-photon interference. 

PMID- 25872090
TI  - Simple fully reflective method of scatter reduction in 2D-IR spectroscopy.
AB  - A fully reflective two-dimensional IR (2D-IR) setup is described that enables
      efficient cancellation of scattered light from multiple pulses in the phase
      matched direction. The local oscillator pulse and the pulse that stimulates the
      vibrational echo signal are synchronously modulated (or fibrillated) in time
      maintaining their phase relationships with the echo wavepacket. The modification
      is cost-effective and can be easily implemented on existing 2D-IR instruments,
      and it avoids the addition of dispersive elements into the beam paths. The
      fibrillation results in a decrease of waiting-time resolution of only tens of
      femtoseconds and has no impact on the spectral lineshape, making it a general
      improvement for 2D-IR spectrometers even for weakly or non-scattering samples. 

PMID- 25872091
TI  - Complete trapping of electromagnetic radiation using surface magnetoplasmons.
AB  - Because the dispersion properties of surface magnetoplasmons (SMPs) in a
      magnetized plasmonic material closely depend on its cladding dielectric, it is
      possible to completely trap SMPs in a system consisting of a plasmonic material
      with cladding of a dielectric heterostructure. By using a semiconductor, our
      finite element simulation (performed using the software COMSOL) shows that
      terahertz one-way SMPs in such a system can be completely trapped at the
      interface of the heterostructure and hence, a focused subwavelength-scale hotspot
      with dramatically enhanced field is generated. Moreover, a one-way SMP pulse in
      this system can also be completely trapped, and the wave packet can be compressed
      into a stable hotspot on the subwavelength scale. 

PMID- 25872092
TI  - Moire pattern generation by dual shearing and its modulation by surface plasmon
      resonance.
AB  - A novel surface plasmon resonance (SPR)-mediated Moire fringe generation is
      theoretically and experimentally investigated using a birefringent lens (BL) and
      a Wollaston prism. Birefringent lens having two longitudinally shifted focal
      points provides radial shear, whereas Wollaston prism introduces lateral shear
      between the two radially sheared patterns for mutual orthogonal polarizations.
      Thus Moire-like pattern is produced at the overlapping region of those patterns.
      Brief theory and experimental demonstration of coherent and incoherent Moire
      fringe generation by such dual shearing is presented. The appearance and
      disappearance of Moire pattern with the rotation of the analyzer axis has also
      been demonstrated. A modified experimental setup has also been developed to
      observe the influence of plasmonic excitation on such patterns which can be
      further utilized for photonic applications such as sensing and imaging. 

PMID- 25872093
TI  - Multi-resonant optical parametric oscillator based on 2D-PPLT nonlinear photonic
      crystal.
AB  - The aim of this work is to achieve an optical parametric oscillator based on two
      dimensional periodically poled lithium tantalate (2D-PPLT) crystals that are
      designed to allow multiple reciprocal lattice-vector contribution to the quasi
      phase matching scheme. We are particularly interested in the effect of the multi
      wavelength parametric generation performed by the 2D nonlinear photonic crystal
      to achieve a multi-resonant optical parametric oscillator. The performances are
      studied in terms of generation efficiency and multi-wavelength generation. 

PMID- 25872094
TI  - Asymmetric dwell-time statistics of polarization chaos from free-running VCSEL.
AB  - We experimentally report on asymmetric dwell-time statistics of polarization
      chaos dynamics generated from free-running vertical-cavity surface-emitting
      lasers (VCSELs). Theoretically, we explain this behavior by introducing a
      misalignment between the phase and amplitude anisotropy within the spin-flip
      model for VCSELs. It induces an asymmetry in the VCSEL polarization behavior
      which is then responsible for significant changes in the statistics of the
      chaotic mode-hopping with an increase in the average residence time and an
      inversion of the dominant mode. 

PMID- 25872095
TI  - Limits to the information gain from lidar measurements.
AB  - Measurements over the return signal are an integral part of lidar remote sensing
      by which we gather information about the characteristics of specific targets. But
      how much information is gained by performing a given lidar measurement? By
      defining Shannon's mutual information of a lidar observation, here we consider
      the bits of information content on the measurement and describe mathematically
      the capacity of lidar estimates to represent a corresponding property in the
      target. For heterodyne Doppler lidars in particular, we have found simple
      analytical formulas that consider the information gain in mean-frequency
      estimates. 

PMID- 25872096
TI  - Flat-panel see-through three-dimensional display based on integral imaging.
AB  - This study proposes a technique to construct a flat-panel see-through three
      dimensional (3D) display based on integral imaging. This display consists of
      multiple lens arrays, a transparent flat-panel display, and a light-blocking wall
      (LBW). Rays behind the display are reconstructed in front of it by combination of
      the lens arrays and the LBW to provide the see-through function. The combination
      of one of the lens arrays and the transparent flat-panel display produces full
      parallax 3D images, which are superimposed on background images. The experimental
      system is constructed to verify the proposed technique. The see-through and
      superposition capabilities of the experimental system are demonstrated. 

PMID- 25872097
TI  - On the measurement of the Pockels effect in strained silicon.
AB  - We measure the voltage-dependent phase shift in silicon waveguides strained by a
      silicon nitride layer and show that, in our measurements, the phase shift is due
      to free carrier accumulation inside the waveguides. Nonetheless, inverting the
      applied voltage also inverts the applied phase shift-an effect due to a quasi
      static surface charge in the silicon nitride. Since the measured effect is on the
      same order as recently published second-order nonlinearities attributed to the
      Pockels effect, inclusion of these carrier-based effects in the analysis of
      experimental data is of paramount importance. 

PMID- 25872098
TI  - Tomographic phase microscopy with 180 degrees  rotation of live cells in
      suspension by holographic optical tweezers.
AB  - We present a new tomographic phase microscopy (TPM) approach that allows
      capturing the three-dimensional refractive index structure of single cells in
      suspension without labeling, using 180 degrees  rotation of the cells. This is
      obtained by integrating an external off-axis interferometer for wide-field wave
      front acquisition with holographic optical tweezers (HOTs) for trapping and micro
      rotation of the suspended cells. In contrast to existing TPM approaches for cell
      imaging, our approach does not require anchoring the sample to a rotating stage,
      nor is it limited in angular range as is the illumination rotation approach.
      Thus, it allows noninvasive TPM of suspended live cells in a wide angular range.
      The proposed technique is experimentally demonstrated by capturing the three
      dimensional refractive index map of yeast cells, while collecting interferometric
      projections at an angular range of 180 degrees  with 5 degrees  steps. The
      interferometric projections are processed by both the filtered back-projection
      method and the diffraction theory method. The experimental system is integrated
      with a spinning disk confocal fluorescent microscope for validation of the label
      free TPM results. 

PMID- 25872099
TI  - More than one genotype: how common is intracolonial genetic variability in
      scleractinian corals?
AB  - In recent years, a few colonial marine invertebrates have shown intracolonial
      genetic variability, a previously unreported phenomenon. Intracolonial genetic
      variability describes the occurrence of more than a single genotype within an
      individual colony. This variability can be traced back to two underlying
      processes: chimerism and mosaicism. Chimerism is the fusion of two or more
      individuals, whereas mosaicism mostly derives from somatic cell mutations. Until
      now, it remained unclear to what degree the ecologically important group of
      hermatypic (reef building) corals might be affected. We investigate the
      occurrence of intracolonial genetic variability in five scleractinian corals:
      Acropora florida, Acropora hyacinthus, Acropora sarmentosa, Pocillopora species
      complex and Porites australiensis. The main focus was to test different genera
      for the phenomenon via microsatellite markers and to distinguish which underlying
      process caused the genetic heterogeneity. Our results show that intracolonial
      genetic variability was common (between 46.6% for A. sarmentosa and 23.8% for P.
      species complex) in all tested corals. The main process was mosaicism (69 cases
      of 222 tested colonies), but at least one chimera existed in every species. This
      suggests that intracolonial genetic variability is widespread in scleractinian
      corals and could challenge the view of a coral colony as an individual and
      therefore a unit of selection. However, it might also hold potential for colony
      survival under rapidly changing environmental conditions. 

PMID- 25872100
TI  - The psychological impact of undergoing genetic-risk profiling in men with a
      family history of prostate cancer.
AB  - BACKGROUND: The ability to identify men at genetically high-risk of prostate
      cancer (PrCa) would enable screening to be targeted at those most in need. This
      study explored the psychological impact (in terms of general and PrCa-specific
      worry and risk perceptions) on men with a family history of PrCa, undergoing
      prostate screening and genetic-risk profiling, within a research study. METHODS:
      A prospective exploratory approach was adopted, incorporating a sequential mixed
      method design. Questionnaires were completed at two time points to measure the
      impact of undergoing screening and genetic-risk profiling. In-depth interviews
      were completed in a subgroup after all study procedures were completed and
      analysed using a framework approach. RESULTS: Ninety-five men completed both
      questionnaires, and 26 were interviewed. No measurable psychological distress was
      detectable in the group as a whole. The interview findings fell into two
      categories: 'feeling at risk' and 'living with risk'. The feeling of being at
      risk of PrCa is a part of men's lives, shaped by assumptions and information
      gathered over many years. Men used this information to communicate about PrCa
      risk to their peers. Men overestimate their risk of PrCa and have an innate
      assumption that they will develop PrCa. The interviews revealed that men
      experienced acute anxiety when waiting for screening results. CONCLUSIONS:
      Personalised genetic-risk assessments do not prevent men from overestimating
      their risk of PrCa. Screening anxiety is common, and timeframes for receiving
      results should be kept to a minimum. Methods of risk communication in men at risk
      of PrCa should be the subject of future research.

PMID- 25872101
TI  - Amelioration of radiation-induced hematopoietic syndrome by an antioxidant
      chlorophyllin through increased stem cell activity and modulation of
      hematopoiesis.
AB  - Hematopoietic stem cells and progenitor cells (HSPC) are low in abundance and
      exhibit high radiosensitivity and their ability to divide dramatically decreases
      following exposure to ionizing radiation. Our earlier studies have shown
      antiapoptotic, immune-stimulatory, and antioxidant effects of chlorophyllin, a
      constituent of the over the counter drug derifil. Here we describe the beneficial
      effects of chlorophyllin against radiation-induced hematopoietic syndrome.
      Chlorophyllin administration significantly enhanced the abundance of HSPC in
      vivo. It induced a transient cell cycle arrest in lineage-negative cells in the
      bone marrow. However, the chlorophyllin-treated mice exposed to whole body
      irradiation (WBI) had a significantly higher proportion of actively dividing HSPC
      in the bone marrow as compared to only WBI-exposed mice. It significantly
      increased the number of colony forming units (CFUs) by bone marrow cells in vitro
      and spleen CFUs in irradiated mice in vivo. Pharmacokinetic study showed that
      chlorophyllin had a serum half-life of 141.8 min in mice. Chlorophyllin
      upregulated antiapoptotic genes and antioxidant machinery via activation of
      prosurvival transcription factors Nrf-2 and NF-kappaB and increased the survival
      and recovery of bone marrow cells in mice exposed to WBI. Chlorophyllin
      stimulated granulocyte production in bone marrow and increased the abundance of
      peripheral blood neutrophils by enhancing serum levels of granulocyte-colony
      stimulation factor (GCSF). Most importantly, prophylactic treatment of mice with
      chlorophyllin significantly abrogated radiation-induced mortality. Chlorophyllin
      mitigates radiation-induced hematopoietic syndrome by increasing the abundance of
      hematopoietic stem cells, enhancing granulopoiesis, and stimulating prosurvival
      pathways in bone marrow cells and lymphocytes.

PMID- 25872103
TI  - Secrecy, stigma and HIV/AIDS: An introduction.
AB  - This paper situates the articles selected for this special issue of AJAR within
      the context of the Sex and Secrecy conference, from which they emerged and within
      the discourse of secrecy. Secrecy and silence which have characterised the
      HIV/AIDS epidemic in many societies, have been the focus of limited academic
      attention. Yet the power of the secret is evident in multiple spheres. This
      introduction uses the lens of secrecy to enhance our understanding of sexuality.
      One of the themes which ran throughout these papers was that of stigma and its
      links to secrecy and HIV/AIDS. The papers reviewed in this introduction highlight
      an alarming paradox. There is a high level of HIV awareness and unparalleled
      public attention around matters of sexuality and yet the authors in this special
      issue all point to the enormity of stigma and its consequences. 

PMID- 25872102
TI  - Modeling the self-assembly of silica-templated nanoparticles in the initial
      stages of zeolite formation.
AB  - The reaction ensemble Monte Carlo method was used to model the self-assembly and
      structure of silica nanoparticles found in the initial stages of the clear
      solution synthesis of the silicalite-1 zeolite. Such nanoparticles, which
      comprise both silica and organic structure-directing agents (OSDAs), are believed
      to play a crucial role in the formation of silica nanoporous materials, yet very
      limited atomic-level structural information is available for these nanoparticles.
      We have modeled silica monomers as flexible tetrahedra with spring constants
      fitted in previous work to silica bulk moduli and OSDAs as spheres attracted to
      anionic silica monomers. We have studied one-step and two-step formation
      mechanisms, the latter involving the initial association of silica species and
      OSDAs driven by physical solution forces, followed by silica
      condensation/hydrolysis reactions simulated with reaction ensemble Monte Carlo.
      The two-step process with preassociation was found to be crucial for generating
      nearly spherical nanoparticles; otherwise, without preassociation they exhibited
      jagged, ramified structures. The two-step nanoparticles were found to exhibit a
      core-shell structure with mostly silica in the core surrounded by a diffuse shell
      of OSDAs, in agreement with SANS and SAXS data. The Qn distribution, quantifying
      silicon atoms bound to n bridging oxygens, found in the simulated nanoparticles
      is in broad agreement with (29)Si solid-state NMR data on smaller, 2 nm
      nanoparticle populations. Ring-size distributions from the simulated
      nanoparticles show that five-membered rings are prevalent when considering
      OSDA/silica mole fractions (~0.2) that lead to silicalite-1, in agreement with a
      previous IR and modeling study. Nanoparticles simulated with higher OSDA
      concentrations show ring-size distributions shifted to smaller rings, with three
      membered silica rings dominating at an OSDA/silica mole fraction of 0.8. Our
      simulations show no evidence of long-range silicalite-1 order in these
      nanoparticles. 

PMID- 25872104
TI  - Contexts of vulnerability: Sex, secrecy and HIV/AIDS.
AB  - Written before the announcement of a national roll out of antiretroviral
      treatment in South Africa, this paper uses three illustrative vignettes to draw
      attention to some major areas of HIV/AIDS vulnerability related to the themes of
      sex and secrecy within households and families. The vulnerability, particularly
      of women and young girls, within domains traditionally regarded as 'safe', is
      noted. The dangers for the spread of the epidemic, of the typical 'silence'
      between generations around sex and the immersion of the younger generation in
      worlds which are essentially hidden from adults, is also commented upon. The
      silence of stigma and nondisclosure are, further, argued to be essentially
      inimical to sociability and what has been referred to by various sociologists as
      communitas, community and to the open expression of love, caring and recognition
      for basic humanity. Even the confidentiality enjoined by law and medical ethics
      is seen to have a negative side, when it comes to caring for and comforting AIDS
      infected and affected family and community members. The paper ends with a call
      for researchers to be aware that AIDS stigma may render the very act of research
      a source of danger to those affected by HIV and AIDS. 

PMID- 25872105
TI  - HIV/AIDS stigma: The latest dirty secret.
AB  - The rejection of HIV/AIDS stigma is based on the understanding that all acts of
      social exclusion relating to HIV/AIDS are not only morally wrong but also
      counterproductive to effective HIV/AIDS prevention and treatment. There is some
      survey evidence suggesting that HIV/AIDS stigma has already diminished
      substantially over time both in South Africa and worldwide. However, it is
      arguable that these surveys are failing to measure the changing face of stigma
      effectively. This paper describes some of the conceptual and methodological
      challenges that quantitative research measuring stigma needs to address. Foremost
      amongst these is the fact that HIV/AIDS stigma stems from multiple sources which
      cannot be conflated if stigma is to be properly identified, measured and most
      importantly, addressed. 

PMID- 25872106
TI  - 'Dear diary I saw an angel, she looked like heaven on earth': Sex talk and sex
      education.
AB  - In this paper we highlight and address some of the problems involved in teaching
      HIV/AIDS education in southern and eastern Africa, and especially in generating
      open discussion among pupils about sex and sexuality. The paper draws on the
      findings of a UNICEF-funded study, in which we were involved, as research
      consultants (2001). The study focused on 'young people, gender, sexuality and
      HIV/AIDS education' and was conducted in Botswana, Kenya, Rwanda, South Africa,
      Tanzania, Zambia and Zimbabwe. In Botswana, Rwanda and Kenya, teachers and young
      people were interviewed about their attitudes towards and experiences of
      teaching/learning HIV/AIDS education. Young people were also interviewed more
      generally, in all the countries, about what it was like being a boy or girl of
      their age. We argue that HIV/AIDS education, as it is commonly taught, as a
      series of moral injunctions (against pre marital sex) effectively silences young
      people, and means that sex 'becomes' naughty when they do talk about it. We
      propose HIV/AIDS pedagogies, which emulate the practices our researchers adopted
      when researching the identities and views of boys and girls, especially
      concerning gender and sexuality. By addressing young people as experts about
      themselves and in a holistic and non-judgemental way, our interviewees were able
      to speak about anxieties and pleasures, many of which related to sexuality. This,
      they had not been able to do with other adults, and even with other children. We
      focus on the regulation and production of gender identities through the ways boys
      and girls talked about sex in our interviews and also in their participation in
      HIV/AIDS classes. In particular we look at how boys and girls 'performed' gender
      when discussing sexuality with boys often very loud and girls quiet, with boys
      presenting themselves as sexual and girls presenting themselves as asexual. We
      argue for approaches to HIV/AIDS education which challenge gender power relations
      without alienating boys by problematising them, and without reproducing
      stereotypes of boys as subjects and girls as objects of sexual desire. We examine
      the implications of this for single sex and mixed group work and for addressing
      'sexual harassment'. Importantly, we found that both girls and boys described
      people of the opposite sex and heterosexual desire very differently in mixed-sex
      group interviews and in the diaries they kept. Rather than addressing girls and
      boys as unitary gendered subjects, we argue for approaches in HIV/AIDS education,
      which are responsive to the different and contradictory ways boys and girls
      present themselves and talk about sexual desire and the opposite sex in different
      contexts. 

PMID- 25872107
TI  - The [in]visibility of HIV/AIDS in the Malawi public sphere.
AB  - This paper argues that, far from being invisible, issues of sexuality are
      omnipresent in the African public sphere. However, this presence is not usually
      found in the medical nor overtly gender/sexual arenas but in general social
      contexts. Western derived research models have sought and continue to seek to
      situate gender and sexual discourse in overt forms, especially when emphasising
      public health aspects. Using qualitative and quantitative evidence from my PhD
      research of popular discourse in Malawi, and using some evidence from Zambia,
      Zimbabwe and South Africa, I argue that the perceived secrecy is allied to
      cultural, male/female and intra-female power relations. I found that significant
      issues of sexual and medical concerns were 'hidden' in the easy to decode public
      social sphere. Using a historical model of the colonial and postcolonial
      construction of this dominant social public sphere in Malawi I was able to
      demonstrate that key messages relating to sexuality and sexual behaviour can be
      easily found in social discourse, from where they can be exploited for health
      promotion purposes. 

PMID- 25872108
TI  - The young, the rich, and the beautiful: Secrecy, suspicion and discourses of AIDS
      in the South African lowveld.
AB  - This article investigates emic accounts of the AIDS deaths that have occurred in
      a village in the Bushbuckridge district of the South African lowveld. I argue
      that whilst AIDS was publicly hidden and shrouded in secrecy, private gossip
      created moral scripts about those suspected of having died of AIDS. Details of 47
      AIDS deaths revealed that young women and relatively wealthy, sometimes powerful
      men were vulnerable to AIDS. I suggest that AIDS constitutes a moral crisis;
      peoples' sexual secrets and desires for commodities and sex featured prominently
      in local AIDS discourses. The article explores the similarity between AIDS and
      witchcraft as a metaphorical analogy. Both were highly secretive, and subjective,
      and circumstantial evidence identified witches and AIDS victims. AIDS and
      witchcraft were also concerned with the problem of unnatural and uncontrolled
      desire. The article explores these themes with regard to men and women's
      experiences respectively. Young 'beautiful women' who used sex to acquire wealth
      were said to 'buy their own coffins' (die of AIDS), yet relationships with
      wealthy men ensured household survival. Relatively affluent men were labelled
      incorrigible 'womanisers' who spread AIDS. Discourses of masculine sexuality
      focussed on men's lack of agency in sexual decision making. The article points to
      the tendency to ignore men's vulnerability and its implications for AIDS
      prevention. 

PMID- 25872109
TI  - Challenging dominant norms of masculinity for HIV prevention.
AB  - Within South Africa there is a growing HIV epidemic, particularly among young
      heterosexual people. A recent report (NMF/HSRC, 2002) indicates that levels of
      HIV infection among young people aged 15-24 years are 9.3% although other studies
      in more specific locations have shown levels to be higher than this. One of the
      best means of developing successful and innovative HIV prevention programmes for
      young people is to enhance our understandings of youth sexuality and the manner
      in which dominant norms contribute to the spread of sexually transmitted
      diseases. Social norms of masculinity are particularly important in this regard,
      as the manner in which 'normal' men are defined such as through acquisition of
      multiple partners, power over women and negative attitudes towards condoms, are
      often in conflict with the true emotional vulnerabilities of young men. Given the
      strong influence of peer groups on young people and the belief that one of the
      solutions to behaviour change lies in peer renegotiation of dominant norms, there
      is the need to begin to investigate young men who challenge dominant norms of
      masculinity. It is in investigating their points of view that a platform for the
      deconstruction of stereotypical masculinities and the reconstruction of new norms
      can be formed. The paper begins to consider these counter normative ideas through
      highlighting the discussions of young South African men aged 13-25 years in focus
      groups and in-depth individual interviews conducted in Gauteng Province. It is
      apparent that among this group there are young men challenging normative views of
      masculinity in a manner that could be harnessed within HIV prevention
      initiatives. 

PMID- 25872110
TI  - Smoking is a predictor of adverse pathological features at radical prostatectomy:
      Results from the Shared Equal Access Regional Cancer Hospital database.
AB  - OBJECTIVE: To test the relationship of smoking and aggressive prostate cancer in
      men undergoing radical prostatectomy. METHODS: A retrospective analysis of 2290
      men who underwent radical prostatectomy from the Shared Equal Access Regional
      Cancer Hospital database from 2000 to 2013 was carried out. There were 1592 (70%)
      non-smokers and 698 (30%) smokers at radical prostatectomy. Logistic regression
      was used to examine whether smoking predicted Gleason score (>=4 + 3), margin
      status, extracapsular extension or seminal vesicle invasion. Linear regression
      was used to test the relationship between smoking and tumor volume. RESULTS:
      Smokers were younger, more likely to be black, had lower body mass index, higher
      pathological Gleason score, more positive margins and extracapsular extension
      (all P < 0.05) versus non-smokers. On crude analysis, smoking was associated with
      positive margins (odds ratio 1.32; P = 0.003) and extracapsular extension (odds
      ratio 1.26; P = 0.036). After adjusting for multiple clinical factors, smoking
      remained associated with a 19-35% increased risk of every adverse feature
      studied, though only the association with extracapsular extension reached
      significance. On multivariable analysis, a trend for smokers to have larger tumor
      volumes (geometric mean 5.8 vs 5.3 g; P = 0.062) was found. CONCLUSIONS: In
      patients undergoing radical prostatectomy, there seems to be a trend for smokers
      to have worse pathological features compared with non-/former smokers. If
      confirmed in future studies, smoking should be considered a modifiable risk
      factor for aggressive prostate cancer.

PMID- 25872111
TI  - A path forward for genomic nursing research.

PMID- 25872112
TI  - Vitamin D3 Treatment Decreases Frequencies of CD16-Positive and TNF-alpha
      Secreting Monocytes in Asthmatic Patients.
AB  - BACKGROUND: Previously, we demonstrated that glucocorticoid (GC) treatment of
      asthmatic patients resulted in decreasing frequencies of monocyte subsets
      expressing CD16 and capable of releasing TNF-alpha. Here, we wished to analyze
      whether the active form of vitamin D, i.e. vitamin D3, referred to as 1alpha,25
      dihydroxyvitamin D3 [1,25-(OH)2D3] can exert GC-like proapoptotic effects on CD16
      positive monocytes and thus decrease the proinflammatory potential of these
      cells. Finally, we set out to investigate whether the addition of 1,25-(OH)2D3
      would facilitate the use of lower doses of GC without decreasing their anti
      inflammatory properties. METHODS: Peripheral blood mononuclear cells collected
      from healthy individuals and asthmatic patients were cultured with 1,25-(OH)2D3
      and/or varying doses of GC in the presence or absence of caspase inhibition. The
      cells were either directly stained for extracellular markers or prestimulated
      with lipopolysaccharide for the assessment of intracellular cytokine production
      and then analyzed by flow cytometry. RESULTS: We found that 1,25-(OH)2D3 alone
      (and in combination with GC) decreased the frequency of CD14++CD16+ and
      CD14+CD16++ monocytes from asthmatic patients and significantly diminished TNF
      alpha production by the monocytes. With regard to the CD14+CD16++ subset, the
      monocyte-depleting effects of 1,25-(OH)2D3 were abrogated in the presence of pan
      caspase inhibitor, suggesting a proapoptotic mechanism of 1,25-(OH)2D3 action.
      Interestingly, we found that a combined treatment of 1,25-(OH)2D3 and GC allowed
      for a 5-fold reduction of the GC dose while maintaining their anti-inflammatory
      effects. CONCLUSIONS: This study has revealed novel immunomodulatory properties
      of 1,25-(OH)2D3 directed against monocyte subsets capable of TNF-alpha
      production. In addition, our data suggest that the introduction of 1,25-(OH)2D3
      to anti-inflammatory therapy would possibly allow for the use of lower doses of
      GC.

PMID- 25872113
TI  - Opioid-induced hyperalgesia: where are we now?
AB  - PURPOSE OF REVIEW: Patients receiving chronic opioid treatment who develop
      paradoxical pain sensations, as well as worsening existing pain, can be diagnosed
      as suffering from opioid-induced hyperalgesia (OIH). As the worldwide population
      expands so too does the proportion of patients who experience pain that requires
      a strong opioid. Recognizing the symptoms of OIH and optimizing the use of
      morphine in the hospital setting is imperative. This review focuses on clinical
      data relating to evidence of OIH at the bedside and the novel techniques employed
      by healthcare providers in order to improve the heightened pain sensations
      experienced by susceptible patients. RECENT FINDINGS: An increasing number of
      randomized prospective controlled trials report worsening patient pain following
      high-dose opioid treatment. Patient case reports support the premise that OIH is
      a clinical reality. According to recent literature, for those individuals who
      develop paradoxical pain sensations upon chronic opioid therapy, the most
      successful course of action involves a multidisciplinary attack that usually
      comprises early diagnosis, opioid switching and adjunct therapies. SUMMARY:
      Looking to the future, improved clinician-patient communication, advanced
      diagnostic techniques and a refinement of prescribed adjunct pharmacotherapies
      will offer the most successful multimodal pain management approach to the problem
      of OIH.

PMID- 25872114
TI  - Procalcitonin as a biomarker for infection-related mortality in cancer patients.
AB  - PURPOSE OF REVIEW: Infectious diseases are the second leading cause of death
      following direct cancer-related complications in the field of oncology. Clinical
      studies using the classic inflammatory biomarkers, C-reactive protein,
      erythrocyte sedimentation rate, leukocytosis, and thrombocytosis fail to show a
      significant correlation between these biomarkers and infection-related mortality.
      It is therefore crucial to define new biomarkers that are not affected by the
      primary cancer and precisely show the severity of the infection to help in the
      decision-making process. RECENT FINDINGS: A significant increase in the number of
      cancer patients in the past decades has created an exponential increase in the
      number of immunocompromised patients. Preemptive and typically unnecessary usage
      of broad-spectrum antibiotics is common during the treatment of these patients
      and may result in an increase in multidrug-resistant microbial strains. Recent
      clinical studies suggest that a significant reduction in antibiotic consumption
      may be achieved by procalcitonin-guided algorithms without sacrificing the
      outcome of patients with severe infection. SUMMARY: In this article, we focus on
      procalcitonin and its potential role in differentiating cancer and infection
      induced inflammation. Using this strategy may significantly reduce the usage of
      empirical broad-spectrum antibiotics and result in earlier discharge of patients.

PMID- 25872115
TI  - Is ginger beneficial for nausea and vomiting? An update of the literature.
AB  - PURPOSE OF REVIEW: Nausea and vomiting can pose a significant burden to patients
      in a variety of clinical settings. Previous evidence suggests that ginger may be
      an effective treatment for these symptoms; however, current evidence has been
      mixed. This article discusses recent clinical trials that have investigated
      ginger as a treatment for multiple types of nausea and vomiting. In addition, the
      potential mechanisms of action of ginger will be discussed. RECENT FINDINGS: This
      article identified nine studies and seven reviews that investigated ginger for
      morning sickness, postoperative nausea and vomiting, chemotherapy-induced, and
      antiretroviral-induced nausea and vomiting. All studies reported that ginger
      provided a significant reduction in nausea and vomiting; however, the clinical
      relevance of some studies is less certain. Common limitations within the
      literature include the lack of standardized extracts, poorly controlled or
      blinded studies, and limited sample size. In addition, recent evidence has
      provided further support for 5-HT3 receptor antagonism as a mechanism by which
      ginger may exert its potentially beneficial effect on nausea and vomiting.
      SUMMARY: The results of studies in this article suggest that ginger is a
      promising treatment for nausea and vomiting in a variety of clinical settings and
      possesses a clinically relevant mechanism. However, further studies are required
      to address the limitations in the current clinical literature before firm
      recommendations for its use can be made.

PMID- 25872117
TI  - Host-microbe cross talk in cancer therapy.
AB  - PURPOSE OF REVIEW: Microbiota secrete a multitude of factors that either confer
      virulence or promote colonization because they are continuously challenged by
      host immune responses. The dynamic interplay between the host's immune response
      and microbiota eventually determines the outcome for the host: health or disease.
      Toll-like receptors (TLRs) play a key role in this interplay as they can
      recognize both microbial and host-derived ligands on the basis of the context in
      which recognition occurs. RECENT FINDINGS: Evidence is accumulating that
      conventional cancer therapies alter interactions and cross talks between the host
      and microbiota. This has been shown for intestinal mucositis, a common side
      effect of various cancer therapies. Advances have been made in the development of
      new and less toxic cancer strategies. One promising field is immunotherapy on the
      basis of TLR activation through recognition of microbial-associated molecular
      patterns. SUMMARY: Evidence is emerging, indicating that existing cancer
      therapies have implications on the composition and functionality of the host
      microbiota environment. This may favor the colonization of pathogens and build up
      the overall toxicity of the drug. Exploitation of the host-microbiota cross talks
      mediated by TLRs is an emerging and promising field in the search for new, less
      toxic anticancer strategies.

PMID- 25872116
TI  - Probiotics to prevent gastrointestinal toxicity from cancer therapy: an
      interpretive review and call to action.
AB  - PURPOSE OF REVIEW: There is currently an unmet need for agents that can prevent
      the gastrointestinal toxicity (mucositis and enteritis) associated with
      chemotherapy and radiation therapy of abdominal and pelvic cancers. Herein we
      provide an overview of how manipulation of the gut microbiota by probiotic
      administration affects these gastrointestinal symptoms. We focus this review on
      published human trials and also provide suggestions on how the field can move
      forward. RECENT FINDINGS: Several clinical trials of varying design, patient
      populations and probiotic products have been reported. Lactobacillus probiotics
      of adequate dosage demonstrate a potential to reduce gastrointestinal toxicity
      when administered prophylactically. Common study limitations prevent the
      widespread adoption of this practice at this point but are informative for
      rational design of future trials. SUMMARY: No single probiotic strain or product
      has emerged from human clinical trials for this indication. Further human studies
      are required to address limitations in the current literature. Preclinical model
      data should be used to inform the rational design of these new clinical trials to
      adequately address this important question.

PMID- 25872118
TI  - Glucagon-like peptides 1 and 2: intestinal hormones implicated in the
      pathophysiology of mucositis.
AB  - PURPOSE OF REVIEW: Chemotherapy often causes adverse effects, including pain,
      bloating, diarrhea, and inflammation and ulceration of the mucous membranes
      lining the digestive tract, which are collectively referred to as mucositis.
      Unfortunately, no remedy has been found yet to manage these side-effects. RECENT
      FINDINGS: The intestinal glucagon-like peptide-2 (GLP-2) is secreted from the
      intestinal endocrine L cells after nutrient intake, but recent findings show that
      the peptide concentration in the plasma also rises after intestinal injury and
      that GLP-2 receptor activation is crucial for intestinal healing. The
      antidiabetic hormone GLP-1, cosecreted with GLP-2, diminished mucositis in an
      animal model of the condition. Therefore, both peptides could be involved in the
      pathophysiology of mucositis. SUMMARY: The intestinal GLPs have shown beneficial
      effects in experimental trials and have potential for therapeutic use. In type 2
      diabetic and obese patients, GLP secretion is impaired. Elucidating the role of
      these endogenous hormones could lead to the identification of mucositis risk
      factors and an alternative preventive therapy for these patients.

PMID- 25872119
TI  - Emerging potassium channel targets for the treatment of pain.
AB  - PURPOSE OF REVIEW: Poor management of chronic pain remains a significant cause of
      misery with huge socioeconomic costs. Accumulating research in potassium (K+)
      channel physiology has uncovered several promising leads for the development of
      novel analgesics. RECENT FINDINGS: We now recognize that certain K+ channel
      subunits are directly gated to pain-relevant stimuli (Kv1.1, K2P) whereas others
      are specifically modulated by inflammatory processes (Kv7, BKCA, K2P). Genetic
      analyses illustrate that K+ channel gene variation can predict pain sensitivity
      (KCNS1, GIRKs), risk for persistent pain (KCNS1, GIRKs, TRESK) and analgesic
      effectiveness (GIRK2). Importantly, preclinical studies confirm that K+ channel
      dysfunction can be a pain trigger in traumatic neuropathies (Kv9.1/Kv2.1, Kv7,
      Kv1.2) and migraine (TRESK). Finally, emerging data suggest that even pain in
      diabetes, bone cancer and autoimmune neuropathies may have K+ channel dysfunction
      constituents. SUMMARY: There is a long-sought need for superior pharmacotherapy
      of pain syndromes. Although universal enhancement of K+ channel function in the
      periphery can decrease nociceptive excitability irrespective of the underlying
      cause, a more refined targeting of subunits with dominant nociceptive roles could
      yield highly efficacious treatments with fewer side-effects. The ongoing
      characterization of molecular interactions linking K+ channel dysfunction to pain
      is instrumental for identifying candidates with the most therapeutic potential.

PMID- 25872120
TI  - Nausea and vomiting induced by gastrointestinal radiation therapy: current status
      and future directions.
AB  - PURPOSE OF REVIEW: Radiation therapy-induced nausea and vomiting (RINV) are
      common and troublesome symptoms among patients receiving radiation therapy for
      gastrointestinal cancers. Their impact on function, quality of life and,
      ultimately, cancer control warrant a review of their incidence, underlying
      mechanisms, treatments and research themes. RECENT FINDINGS: Research in RINV is
      underrepresented relative to that in chemotherapy-induced nausea and vomiting.
      The incidence of RINV among patients receiving modern day radiation therapy is
      questioned and supportive care practice patterns vary among radiation
      oncologists. Antiemetic guideline recommendations for prophylactic and rescue
      therapy are based solely on the anatomic region being irradiated and not other
      patient-related, radiation therapy-related, or organ-specific dosimetric factors
      that likely modulate the risk of RINV. Dosimetric predictors are likely the most
      attainable biomarker moving forward, but only early steps have been taken. The
      small bowel and stomach will be the best first candidates for study among
      patients with gastrointestinal cancers. Studies of the mechanisms underlying RINV
      are conspicuously lacking. A new generation of observational studies and
      therapeutic clinical trials is needed, and more attention must be given to the
      relative impact of nausea and vomiting on the function and quality of life among
      specific homogeneous patient populations. SUMMARY: Optimal supportive care
      strategies for RINV following radiation therapy for gastrointestinal cancers are
      lacking, and will not be known until future research answers the many open
      questions regarding the mechanisms underlying RINV, the true incidence and impact
      of these symptoms among patients and the best way to predict and mitigate them.

PMID- 25872121
TI  - Simultaneous targeting of multiple opioid receptor types.
AB  - PURPOSE OF REVIEW: This article aims to discuss the multitarget concept for
      opioid receptor ligands framed on early observations that activating MOP (mu:MU)
      receptor whilst simultaneously blocking DOP (delta:delta) receptors reduces the
      onset of morphine tolerance. The review period is ostensibly calendar year 2014
      but the new work in 2013 is also covered. RECENT FINDINGS: Two molecules of
      interest with MOP agonist/DOP agonist and MOP agonist/DOP antagonist profiles
      were described: Rv-Jim-C3 and 3-[(2R,6R,11R)-8-hydroxy-6,11-dimethyl-1,4,5,6
      tetrahydro-2,6-methano-3-benzazocin-3(2H)-yl]-N-phenylpropanamide (LP1),
      respectively. Both were effective in neuropathic pain (wherein classical single
      target opioids have low efficacy) with the latter having a predicted reduced
      tolerance profile. BU0807 is a buprenorphine derivative with mixed MOP/NOP
      agonist activity and this was shown to be effective in abdominal pain. SR16435
      and GRT6005 (cebranopadol) are mixed MOP/MOP agonists with varying degrees of
      partial agonism. Both displayed significant antinociceptive activity and reduced
      tolerance potential in preclinical models. SUMMARY: There is growing evidence for
      and interest in the design and evaluation of mixed opioids that extend beyond the
      MOP/DOP pairing to now include NOP. Indeed, a mixed MOP/NOP ligand is close to
      the clinic; this will reinvigorate the search for other mixed molecules with
      reduced side-effect profiles.

PMID- 25872122
TI  - Pain: nonmalignant disease.

PMID- 25872123
TI  - Gastrointestinal toxicities from targeted therapies: measurement, duration and
      impact.
AB  - PURPOSE OF REVIEW: Gastrointestinal toxicities deriving from targeted therapies
      are main issues in the oncologic setting, as they can negatively impair quality
      of life, reducing patient's adherence to treatment and dose intensity, so
      ultimately possibly affecting outcome. We reviewed some methodological questions
      linked to the assessment of this kind of toxicity, in terms of way of
      measurement, duration of the assessed toxicity and impact on the global treatment
      program. RECENT FINDINGS: The scale of toxicity assessment may influence the
      evaluation itself; reporting the adverse events by the physician is generally
      less accurate than by the patient, and these two modalities should be integrated
      in the analysis of gastrointestinal toxicities by targeted treatment. Moreover,
      the duration of the symptoms and the attention to the lower grade toxicities
      estimation are generally underreported in clinical trials. The factors that may
      affect treatment's adherence by the patient are discussed, as they are strictly
      linked to the appearance and intensity of gastrointestinal toxicities. SUMMARY:
      Methodological issues should be considered in designing new trials with targeted
      therapies and evaluating the way of assessment of adverse events, mainly
      gastrointestinal.

PMID- 25872124
TI  - Neuroimmune mechanisms in cancer pain.
AB  - PURPOSE OF REVIEW: The current review provides a summary of recent advances in
      our understanding of the neuroimmune interactions which influence the development
      of pain associated with cancer. RECENT FINDINGS: Common signalling pathways,
      mediators and immune cell types are involved in the generation of pain as a
      result of both cancer and its treatment. Distinct alterations in central and
      peripheral neuronal function occur in multiple forms of cancer pain. Other more
      unusual neuroimmune processes such as graft-versus-host disease may cause cancer
      pain. SUMMARY: Identification of the cellular processes which underlie the
      generation of cancer pain provide potential novel targets for drug development
      and may eventually lead to improved pain management for cancer patients.

PMID- 25872125
TI  - Editorial Comment: Does gut-derived inflammation enhance pain signaling following
      chemotherapy in a Toll-like receptor 4-dependent manner?

PMID- 25872126
TI  - Long-term effectiveness of a community-based model of care in Maori and Pacific
      patients with type 2 diabetes and chronic kidney disease: a 4-year follow up of
      the DElay Future End Stage Nephropathy due to Diabetes (DEFEND) study.
AB  - BACKGROUND/AIM: The Delay Future End Stage Nephropathy due to Diabetes study was
      a randomised controlled trial of Maori and Pacific patients with advanced
      diabetic nephropathy, comparing a community-based model of care with usual care.
      The intervention group achieved lower blood pressure (BP), proteinuria and less
      end-organ damage. After the intervention ended, all patients reverted to usual
      care, and were followed to review the sustainability of the intervention.
      METHODS: A retrospective observation of 65 patients (aged 47-75 years) with type
      2 diabetes, hypertension, chronic kidney disease 3/4 and proteinuria (>0.5 g/day)
      previously randomised to intervention/community care or usual care for 11-21
      months. Follow up thereafter was until death, end-stage renal disease (ESRD)
      (estimated glomerular filtration rate (eGFR) <= 10 mL/min/1.73 m(2) )/dialysis or
      1 February 2014. Primary end-points were death and ESRD/dialysis. Secondary
      outcomes were annualised glomerular filtration rate decline, non-fatal vascular
      events and hospitalisations. RESULTS: Median (interquartile ranges (IQR)) post
      trial follow up was 49 (21-81) months and similar in both groups. The median
      (IQR) eGFR decline was -3.1 (-5.5, -2.3) and -5.5 (-7.1, -3.0) mL/min/year in the
      intervention and usual care groups respectively (P = 0.11). Similar number of
      deaths, renal and vascular events were observed in both groups. At the end of
      follow up, the number of prescribed antihypertensive medications was similar (3.4
      +/- 1.0 vs 3.3 +/- 1.4; P = 0.78). There were fewer median (IQR) hospital days (8
      (3, 18) vs 15.5 (6, 49) days, P = 0.03) in the intervention group. CONCLUSIONS:
      Short-term intensive BP control followed by usual care did not translate into
      reduction in long-term mortality or ESRD rates, but was associated with reduced
      hospitalisations.

PMID- 25872127
TI  - FOLFIRINOX-based neoadjuvant therapy in borderline resectable or unresectable
      pancreatic cancer: a meta-analytical review of published studies.
AB  - OBJECTIVE: The use of neoadjuvant chemotherapy can enable surgical resection of
      borderline resectable or unresectable pancreatic cancer (PC). The aim of this
      study was to evaluate the effectiveness of the multiagent 5-fluorouracil +
      oxaliplatin + irinotecan + leucovorin (FOLFIRINOX) regimen as a neoadjuvant
      treatment for PC. METHODS: Studies in which FOLFIRINOX with or without
      radiotherapy was given before surgery to patients with borderline resectable or
      unresectable PC were analyzed using a meta-analytical approach. The primary
      outcomes were resection rate and radical (R0) resection rate. Data were expressed
      as weighted pooled proportions with 95% confidence intervals (CIs). RESULTS:
      Thirteen studies, with a total of 253 patients, were included in this meta
      analysis. After undergoing the treatment, 43% (95% CI, 32.8-53.8) of patients
      were resected and 39.4% (95% CI, 32.4-46.9) underwent R0 resection (85% of
      surgical specimens). In particular, among borderline resectable PCs, R0 resection
      was possible in 63.5% (95% CI, 49%-76%) of the cases. The rate of R0 resection in
      unresectable PCs was 22.5% (95% CI, 13.3-35.4). CONCLUSIONS: This meta-analysis
      shows that down-staging after neoadjuvant FOLFIRINOX-based therapy is noticeable
      in patients with borderline resectable/unresectable PC, with a total R0 resection
      rate of 40%.

PMID- 25872128
TI  - Pancreatic cancer disparities in African Americans.
AB  - OBJECTIVES: Pancreatic cancer is the fourth leading cause of cancer-related
      deaths in the United States. The incidence of pancreatic cancer in African
      Americans is 50% to 90% higher than the incidence in other racial groups. African
      Americans also have the worst prognosis. This is an evidence-based review of
      pancreatic cancer in African Americans with particular emphasis on baseline
      characteristics, treatment, and survival. METHODS: We queried PubMed in search
      for articles describing racial disparities in pancreatic cancer. Two categories
      of terms were "anded" together: pancreatic cancer terms and race terms. The last
      search was performed on November 14, 2013. RESULTS: We summarized the data on
      pancreatic cancer baseline characteristics, treatment, and survival for African
      Americans that we obtained from the following databases: (1) Surveillance,
      Epidemiology, and End Results, 1988-2008; (2) California Cancer Registry 1988
      1998; (3) Cancer Survivor Program of Orange County/San Diego Imperial
      Organization for Cancer Control, 1988-1998; and (4) Harris County, 1998-2010.
      CONCLUSIONS: Overall, pancreatic cancer survival of African Americans has not
      significantly improved over the past several decades despite advances in
      multimodality therapy; African Americans continue to face worse outcomes than
      whites. Although baseline characteristics, treatment, and biological factors
      offer some explanation, they do not completely explain the disparities in
      incidence and survival.

PMID- 25872129
TI  - The chemokine receptors CXCR4/CXCR7 and their primary heterodimeric ligands
      CXCL12 and CXCL12/high mobility group box 1 in pancreatic cancer growth and
      development: finding flow.
AB  - Novel therapies need to be developed for patients with pancreatic cancer because
      of the poor outcomes of current regimens. Pancreatic cancer cells respond to the
      C-X-C chemokine receptor type 4 (CXCR4)/C-X-C chemokine receptor type 7 (CXCR7)/C
      X-C motif chemokine 12 (CXCL12)/high-mobility group box 1 signaling axis and this
      axis presents a novel target for therapy. C-X-C motif chemokine 12 stimulates
      CXCR4/CXCR7-bearing cells in a paracrine manner. C-X-C chemokine receptor type 4
      and CXCR7 are transmembrane G protein-coupled receptors that, upon interaction
      with ligand CXCL12, activate downstream protein kinases that promote a more
      aggressive behavior. C-X-C chemokine receptor type 4 is expressed on most
      pancreatic cancer cells, whereas CXCR7 is primarily expressed on tumor-associated
      endothelium. High-mobility group box 1 promotes the CXCR4 and CXCL12 interaction,
      promoting angiogenesis and lymphangiogenesis. Hypoxia-inducible factor 1 is a
      potent stimulator of CXCR4 and CXCL12 expression, promoting more aggressive
      behavior. This receptor/ligand interaction can be disrupted by CXCR4 antagonists
      available and in clinical use to harvest bone marrow stem cells. Novel imaging
      strategies are now being developed at several centers to evaluate response to
      therapy and identify early recurrence. Thus, the CXCR4/CXCR7/CXCL12 interaction
      plays a critical role in cancer cell progression, proliferation, invasion, as
      well as metastasis and is a suitable target for therapy, imaging, as well as
      development of novel diagnostics. 

PMID- 25872130
TI  - The association of smoking and acute pancreatitis: a systematic review and meta
      analysis.
AB  - OBJECTIVES: Cigarette smoking is an independent risk factor for chronic
      pancreatitis. We conducted a systematic review of the literature assessing
      whether cigarette smoking is a risk factor for acute pancreatitis (AP) and
      recurrent AP (RAP). METHODS: MEDLINE, PubMed, Embase, and Cochrane Database of
      Systematic Reviews were searched for studies published from database inception
      through March 2013. Two investigators independently reviewed articles for
      eligibility; discordant decisions were resolved by a third investigator's review
      and consensus. When there were sufficient studies, random-effects meta-analyses
      were performed by estimating pooled hazards ratios (HRs) with 95% confidence
      intervals (CIs). RESULTS: Twelve studies met the eligibility criteria: 7 for AP,
      5 for RAP. Compared with never smokers, the risk for AP was significantly
      increased in current smokers (6 studies; HR, 1.75; 95% CI, 1.26-2.44) and former
      smokers (5 studies; HR, 1.63; 95% CI, 1.18-2.27). Compared with never smokers,
      ever smokers were at higher risk for developing RAP (5 studies; HR, 1.59; 95% CI,
      1.19-2.12). CONCLUSIONS: This meta-analysis provides supportive evidence for the
      association of smoking status and AP. This effect is most pronounced for current
      smokers, but the risk exists among the former smokers compared with never
      smokers. There was an increased risk for RAP among ever smokers compared with
      that among never smokers.

PMID- 25872131
TI  - Analysis of somatostatin receptor 2A immunohistochemistry, RT-qPCR, and in vivo
      PET/CT data in patients with pancreatic neuroendocrine neoplasm.
AB  - OBJECTIVE: Gallium 68 somatostatin receptor (SSTR) positron emission
      tomography/computed tomography (PET/CT) is one of the most sensitive imaging
      methods for pancreatic neuroendocrine tumors. The aim of the study was to
      correlate the receptor density generated from the static PET/CT (maximum standard
      uptake values [SUVmax], mean standard uptake values [SUVmean]) with subtype 2A
      SSTR (SSTR2A) immunohistochemistry and reverse transcriptase-quantitative
      polymerase chain reaction (RT-qPCR) gene-expression data. METHODS: Thirty-nine
      tumor specimens (17 primary pancreatic tumors [PTs], 22 metastases [MTS]) of 19
      patients with PET/CT scans preoperatively were evaluated. Subtype 2A SSTR
      expression was quantified immunohistochemically (immunoreactive score [IRS]) and
      on messenger RNA (mRNA) level by RT-qPCR. RESULTS: The PT and MTS did not differ
      significantly in their SUVmax (P = 0.07) but displayed a dissimilarity with
      respect to their SSTR2A expression (mean [SD] IRS PT, 8.8 [3.6] vs mean [SD] IRS
      MTS, 5.1 [4.5]; P = 0.02).The SUVmean was highly significantly correlated to
      SSTR2A mRNA expression (C = 0.85, P < 0.001) and moderately to SSTR2A protein
      expression (C = 0.53, P = 0.05). Moreover, the SUVmax correlated moderately with
      SSTR2A protein expression (C = 0.44, P = 0.03) and mRNA expression (C = 0.64, P =
      0.042). CONCLUSIONS: The SUVmax and SUVmean are reliable ex vivo parameters for
      in vivo quantification of SSTR expression in pancreatic neuroendocrine tumors.
      Both immunohistochemistry and RT-qPCR are comparable methods for SSTR2A
      quantification. The PT and MTS differ significantly in their SSTR2A expression.
      This fact should be taken into account when treating patients with somatostatin
      analogs or peptide receptor radionuclide therapy.

PMID- 25872132
TI  - Somatostatin receptor subtype 2 expression and somatostatin receptor scintigraphy
      positivity in pancreatic serous cystadenomas.

PMID- 25872133
TI  - Mucinous cystic neoplasm of the pancreas with increased IgG4+ plasma cells and
      histopathologic features of autoimmune pancreatitis/IgG4-related disease.

PMID- 25872134
TI  - HNPCC-associated pheochromocytoma: expanding the tumor spectrum.

PMID- 25872135
TI  - Serum markers of myocardial damage in acute pancreatitis: a prospective time
      course study.

PMID- 25872136
TI  - Proton pump inhibitors impact on post-endoscopic retrograde
      cholangiopancreatography pancreatitis.

PMID- 25872137
TI  - Below-ground abiotic and biotic heterogeneity shapes above-ground infection
      outcomes and spatial divergence in a host-parasite interaction.
AB  - We investigated the impact of below-ground and above-ground environmental
      heterogeneity on the ecology and evolution of a natural plant-pathogen
      interaction. We combined field measurements and a reciprocal inoculation
      experiment to investigate the potential for natural variation in abiotic and
      biotic factors to mediate infection outcomes in the association between the
      fungal pathogen Melampsora lini and its wild flax host, Linum marginale, where
      pathogen strains and plant lines originated from two ecologically distinct
      habitat types that occur in close proximity ('bog' and 'hill'). The two habitat
      types differed strikingly in soil moisture and soil microbiota. Infection
      outcomes for different host-pathogen combinations were strongly affected by the
      habitat of origin of the plant lines and pathogen strains, the soil environment
      and their interactions. Our results suggested that tradeoffs play a key role in
      explaining the evolutionary divergence in interaction traits among the two
      habitat types. Overall, we demonstrate that soil heterogeneity, by mediating
      infection outcomes and evolutionary divergence, can contribute to the maintenance
      of variation in resistance and pathogenicity within a natural host-pathogen
      metapopulation. 

PMID- 25872138
TI  - Characterization of the recognition specificity of BH2, a monoclonal antibody
      prepared against the HLA-B27 heavy chain.
AB  - BH2, a monoclonal antibody prepared against the denatured human leukocytic
      antigen-B27 heavy chain (HLA-B27 HC), can immunoprecipitate the misfolded HLA-B27
      HC complexed with Bip in the endoplasmic reticulum and recognize the
      homodimerized HLA-B27 HC that is often observed on the cell membrane of patients
      suffered from ankylosing spondylitis (AS). However, the recognition specificity
      of BH2 toward the other molecules of HLA-B type and toward the different types of
      HLA molecules remained uncharacterized. In this study, we carried out the HLA
      typing by using the Luminex Technology to characterize the recognition
      specificity of BH2 and analyzed the binding domain of HLA-B27 HC by BH2. Our
      results indicated that BH2 preferably binds to molecules of HLA-B and -C rather
      than HLA-A and the binding site is located within the alpha2 domain of HLA-B27
      HC. 

PMID- 25872139
TI  - From ELF to compressibility in solids.
AB  - Understanding the electronic nature of materials' compressibility has always been
      a major issue behind tabulation and rationalization of bulk moduli. This is
      especially because this understanding is one of the main approaches to the design
      and proposal of new materials with a desired (e.g., ultralow) compressibility. It
      is well recognized that the softest part of the solid will be the one responsible
      for its compression at the first place. In chemical terms, this means that the
      valence will suffer the main consequences of pressurization.It is desirable to
      understand this response to pressure in terms of the valence properties(charge,
      volume, etc.). One of the possible approaches is to consider models of electronic
      separability, such as the bond charge model (BCM), which provides insight into
      the cohesion of covalent crystals in analogy with the classical ionic model.
      However, this model relies on empirical parametrization of bond and lone pair
      properties. In this contribution, we have coupled electron localization function
      (ELF) ab initio data with the bond charge model developed by Parr in order to
      analyze solid state compressibility from first principles and moreover, to derive
      general trends and shed light upon superhard behavior.

PMID- 25872140
TI  - Quercetin improves postischemic recovery of heart function in doxorubicin-treated
      rats and prevents doxorubicin-induced matrix metalloproteinase-2 activation and
      apoptosis induction.
AB  - Quercetin (QCT) is flavonoid that possesses various biological functions
      including anti-oxidative and radical-scavenging activities. Moreover, QCT exerts
      some preventive actions in treatment of cardiovascular diseases. The aim of
      present study was to explore effects of prolonged administration of QCT on
      changes induced by repeated application of doxorubicin (DOX) in rat hearts. We
      focused on the ultrastructure of myocardium, matrix metalloproteinases (MMPs),
      biometric parameters, and apoptosis induction. Our aim was also to examine
      effects of QCT on ischemic tolerance in hearts exposed to chronic effects of DOX,
      and to determine possible mechanisms underlying effects of QCT. Our results
      showed that QCT prevented several negative chronic effects of DOX: (I) reversed
      DOX-induced blood pressure increase; (II) mediated improvement of deleterious
      effects of DOX on ultrastructure of left ventricle; (III) prevented DOX-induced
      effects on tissue MMP-2 activation; and (iv) reversed effects of DOX on apoptosis
      induction and superoxide dismutase inhibition. Moreover, we showed that rat
      hearts exposed to effects of QCT were more resistant to ischemia/reperfusion
      injury. Effects of QCT on modulation of ischemic tolerance were linked to Akt
      kinase activation and connexin-43 up-regulation. Taken together, these results
      demonstrate that prolonged treatment with QCT prevented negative chronic effects
      of DOX on blood pressure, cellular damage, MMP-2 activation, and apoptosis
      induction. Moreover, QCT influenced myocardial responses to acute ischemic
      stress. These facts bring new insights into mechanisms of QCT action on rat
      hearts exposed to the chronic effects of DOX. 

PMID- 25872141
TI  - Surface modification of ZnO nanorods with Hamilton receptors.
AB  - A new prototype of a Hamilton receptor suitable for the functionalization of
      inorganic nanoparticles was synthesized and characterized. The hydrogen bonding
      receptor was coupled to a catechol moiety, which served as anchor group for the
      functionalization of metal oxides, in particular zinc oxide. Synthesized zinc
      oxide nanorods [ZnO] were used for surface functionalization. The wet-chemical
      functionalization procedure towards monolayer-grafted particles [ZnO-HR] is
      described and a detailed characterization study is presented. In addition, the
      detection of specific cyanurate molecules is demonstrated. The hybrid structures
      [ZnO-HR-CA] were stable towards agglomeration and exhibited enhanced
      dispersability in apolar solvents. This observation, in combination with several
      spectroscopic experiments gave evidence of the highly directional supramolecular
      recognition at the surface of nanoparticles. 

PMID- 25872142
TI  - Mutation breeding of extracellular polysaccharide-producing microalga
      Crypthecodinium cohnii by a novel mutagenesis with atmospheric and room
      temperature plasma.
AB  - Extracellular polysaccharides (EPS) produced by marine microalgae have the
      potential to be used as antioxidants, antiviral agents, immunomodulators, and
      anti-inflammatory agents. Although the marine microalga Crypthecodinium cohnii
      releases EPS during the process of docosahexaenoic acid (DHA) production, the
      yield of EPS remains relatively low. To improve the EPS production, a novel
      mutagenesis of C. cohnii was conducted by atmospheric and room temperature plasma
      (ARTP). Of the 12 mutants obtained, 10 mutants exhibited significantly enhanced
      EPS yield on biomass as compared with the wild type strain. Among them, mutant M7
      was the best as it could produce an EPS volumetric yield of 1.02 g/L, EPS yield
      on biomass of 0.39 g/g and EPS yield on glucose of 94 mg/g, which were 33.85%,
      85.35% and 57.17% higher than that of the wild type strain, respectively. Results
      of the present study indicated that mutagenesis of the marine microalga C. cohnii
      by ARTP was highly effective leading to the high-yield production of EPS. 

PMID- 25872143
TI  - High insulin levels in KK-Ay diabetic mice cause increased cortical bone mass and
      impaired trabecular micro-structure.
AB  - Type 2 diabetes mellitus (T2DM) is a chronic disease characterized by
      hyperglycemia, hyperinsulinemia and complications, including obesity and
      osteoporosis. Rodents have been widely used to model human T2DM and investigate
      its effect on the skeleton. We aimed to investigate skeletal alterations in
      Yellow Kuo Kondo (KK-Ay) diabetic mice displaying high insulin and glucose
      levels. Bone mineral density (BMD), micro-architecture and bone metabolism
      related genes were analyzed. The total femoral areal BMD (aBMD), cortical
      volumetric BMD (vBMD) and thickness were significantly increased in KK-Ay mice,
      while the trabecular vBMD and mineralized bone volume/tissue volume (BV/TV),
      trabecular thickness and number were decreased compared to C57BL mice. The
      expression of both osteoblast-related genes, such as osteocalcin (OC), bone
      sialoprotein, Type I Collagen, osteonectin, RUNX2 and OSX, and osteoclast-related
      genes, such as TRAP and TCIRG, were up-regulated in KK-Ay mice. Correlation
      analyses showed that serum insulin levels were positively associated with aBMD,
      cortical vBMD and thickness and negatively associated with trabecular vBMD and
      micro-architecture. In addition, serum insulin levels were positively related to
      osteoblast-related and osteoclast-related gene expression. Our data suggest that
      high insulin levels in KK-Ay diabetic mice may increase cortical bone mass and
      impair trabecular micro-structure by up-regulating osteoblast-and osteoclast
      related gene expression. 

PMID- 25872145
TI  - Revisiting the formation and tunable dissociation of a [2]pseudorotaxane formed
      by slippage approach.
AB  - A new [2]pseudorotaxane DB24C8?1-H . PF6 with dibenzo[24]crown-8 (DB24C8) crown
      ether-dibenzylammonium (1-H . PF6) binding which was formed by slippage approach
      at different solvents and temperature, had been isolated and characterized by NMR
      spectroscopy and mass spectrometry. The [2]pseudorotaxane DB24C8?1-H . PF6 was
      stable at room temperature. The dissociation rate of [2]pseudorotaxane DB24C8?1-H
      . PF6 could be tuned by using different stimuli such as triethylamine
      (TEA)/diisopropylethylamine (DIPEA) and dimethyl sulfoxide (DMSO). In particular,
      the dissociation of [2]pseudorotaxane DB24C8?1-H . PF6 by an excess of TEA/DIPEA
      base mixture possessed a long and sustained, complete dissociation over 60 days.
      Other stimuli by DMSO possessed a relatively fast dissociation over 24 h.

PMID- 25872146
TI  - Electronic structures and current conductivities of B, C, N and F defects in
      amorphous titanium dioxide.
AB  - Although titanium dioxide (TiO2) has been extensively studied and widely used in
      energy and environmental areas, the amorphous form and its related defect
      properties are poorly understood. Recent studies, however, have emphasized the
      crucial role of amorphousness in producing competitively good performances in
      photochemical applications. In this work we have investigated for the first time
      the effects of various dopants (B, C, N and F) on charge carrier transport in
      amorphous titanium dioxide (a-TiO2), given that doping is a common technique used
      to tune the electronic properties of semiconductors, and that the existence of
      these impurities could also be unintentionally introduced during the synthesis
      process. The a-TiO2 model was obtained using a classical molecular dynamics
      method, followed by density-functional theory calculations (DFT + U, with Hubbard
      correction term U) on electronic structures and defect states. The formation of
      these impurity defects in a-TiO2 was found to be energetically more favorable by
      several eV than their crystal counterparts (in rutile). The contributions of
      these defect states to the charge transfer processes were examined by means of
      Marcus theory. 

PMID- 25872144
TI  - MicroRNAs regulate bone development and regeneration.
AB  - MicroRNAs (miRNAs) are endogenous small noncoding ~22-nt RNAs, which have been
      reported to play a crucial role in maintaining bone development and metabolism.
      Osteogenesis originates from mesenchymal stem cells (MSCs) differentiating into
      mature osteoblasts and each period of bone formation is inseparable from the
      delicate regulation of various miRNAs. Of note, apprehending the sophisticated
      circuit between miRNAs and osteogenic homeostasis is of great value for
      artificial skeletal regeneration for severe bone defects. In this review, we
      highlight how different miRNAs interact with diverse osteo-related genes and
      endeavor to sketch the contours of potential manipulations of miRNA-modulated
      bone repair. 

PMID- 25872147
TI  - A novel method for room temperature distribution and conservation of RNA and DNA
      reference materials for guaranteeing performance of molecular diagnostics in onco
      hematology: A GBMHM study.
AB  - OBJECTIVES: Performance of methods used for molecular diagnostics must be closely
      controlled by regular analysis of internal quality controls. However,
      conditioning, shipping and long lasting storage of nucleic acid controls remain
      problematic. Therefore, we evaluated the minicapsule-based innovative process
      developed by Imagene (Evry, France) for implementing DNA and RNA controls
      designed for clonality assessment of lymphoproliferations and BCR-ABL1 mRNA
      quantification, respectively. DESIGN & METHODS: DNA samples were extracted from
      12 cell lines selected for giving specific amplifications with most BIOMED-2 PCR
      tubes. RNA samples were extracted from 8 cell line mixtures expressing various
      BCR-ABL1 transcript levels. DNA and RNA were encapsulated by Imagene and shipped
      at room temperature to participating laboratories. Biologists were asked to
      report quality data of recovered nucleic acids as well as PCR results. RESULTS:
      Encapsulated nucleic acids samples were easily and efficiently recovered from
      minicapsules. The expected rearrangements at immunoglobulin, T-cell receptor and
      BCL2 loci were detected in DNA samples by all laboratories. Quality of RNA was
      consistent between laboratories and met the criteria requested for quantification
      of BCR-ABL1 transcripts. Expression levels measured by the 5 laboratories were
      within +/-2 fold interval from the corresponding pre-encapsulation reference
      value. Moreover aging studies of encapsulated RNA simulating up to 100 years
      storage at room temperature show no bias in quantitative outcome. CONCLUSIONS:
      Therefore, Imagene minicapsules are suitable for storage and distribution at room
      temperature of genetic material designed for proficiency control of molecular
      diagnostic methods based on end point or real-time quantitative PCR.

PMID- 25872148
TI  - Validation of the Ion Torrent PGM sequencing for the prospective routine
      molecular diagnostic of colorectal cancer.
AB  - OBJECTIVES: Treatment individualization based on specific molecular biomarkers is
      becoming increasingly important in oncology. In colorectal cancer (CRC), the
      molecular characterization of RAS and BRAF mutation status for prognostic and
      predictive purposes is commonly performed by different validated methods.
      However, as the number of clinically relevant mutations to be analyzed increases,
      the definition of new approaches for more sensitive, rapid and economic patient
      selection urges. To this aim, we evaluated the Ion Semiconductor sequencing using
      the Ion Torrent Personal Genome Machine (IT-PGM) in our routine molecular
      diagnostics for CRC in comparison with the gold standard direct Sanger
      sequencing. DESIGN AND METHODS: Formalin-fixed and paraffin-embedded tumor
      tissues obtained by surgery or biopsy of 66 CRCs were collected. DNA was
      extracted and sequenced by IT-PGM and Sanger method. RESULTS: The proposed IT-PGM
      sequencing strategy exceeded the 500 reads of coverage for all clinically
      relevant RAS/BRAF amplicons in most samples and thus guaranteed optimal
      determination. Indeed, the frequencies and the mutational spectrum of RAS and
      BRAF mutations were in agreement with literature data and revealed 100%
      concordance between the IT-PGM and routine Sanger sequencing approaches.
      Turnaround time and cost evaluation indicate that the IT-PGM sequencing permits
      the characterization of the clinically relevant mutational spots at lower cost
      and turnaround time compared to Sanger sequencing and allows inclusion of
      additional amplicons whose characterization may acquire significance in the very
      next future. CONCLUSION: The IT-PGM is a valid, flexible, sensitive and
      economical method alternative to the Sanger sequencing in routine diagnostics to
      select patients for anti-epidermal growth factor receptor therapy for metastatic
      CRC.

PMID- 25872149
TI  - Selecting appropriate dose regimens for AM-101 in the intratympanic treatment of
      acute inner ear tinnitus.
AB  - Inhibition of cochlear N-methyl-D-aspartate (NMDA) receptors with AM-101, a small
      molecule antagonist delivered by intratympanic injection, represents a novel
      approach to treat acute tinnitus triggered by glutamate excitotoxicity. An
      earlier double-blind, randomized, placebo-controlled phase II clinical trial
      (TACTT0) had demonstrated a significant and dose-dependent improvement in
      tinnitus triggered by acute acoustic trauma or otitis media from baseline to day
      90. A second phase II trial (TACTT1) now sought to evaluate the most appropriate
      dose regimen for this treatment. Outcomes from the TACTT1 trial showed no
      significant difference in tinnitus improvement between a single-dose treatment
      and a dose regimen comprising three doses over 2 weeks. Taken together, three
      injections over 3 consecutive days showed the best results in the two phase II
      trials, suggesting that repeated and concentrated inhibition of cochlear NMDA
      receptors provides best treatment effects, while keeping the procedural impact on
      patients short.

PMID- 25872150
TI  - Home is where the patient is: a ground-level perspective on the Patient-Centered
      Medical Home.

PMID- 25872151
TI  - Racial/Ethnic differences in health care visits made before suicide attempt
      across the United States.
AB  - BACKGROUND: Suicide is a public health concern, but little is known about the
      patterns of health care visits made before a suicide attempt, and whether those
      patterns differ by race/ethnicity. OBJECTIVES: To examine racial/ethnic variation
      in the types of health care visits made before a suicide attempt, when those
      visits occur, and whether mental health or substance use diagnoses were
      documented. RESEARCH DESIGN: Retrospective, longitudinal study, 2009-2011.
      PARTICIPANTS: 22,387 individuals who attempted suicide and were enrolled in the
      health plan across 10 health systems in the Mental Health Research Network.
      MEASURES: Cumulative percentage of different types of health care visits made in
      the 52 weeks before a suicide attempt, by self-reported racial/ethnicity and
      diagnosis. Data were from the Virtual Data Warehouse at each site. RESULTS: Over
      38% of the individuals made any health care visit within the week before their
      suicide attempt and ~95% within the preceding year; these percentages varied
      across racial/ethnic groups (P<0.001). White individuals had the highest
      percentage of visits (>41%) within 1 week of suicide attempt. Asian Americans
      were the least likely to make visits within 52 weeks. Hawaiian/Pacific Islanders
      had proportionally the most inpatient and emergency visits before an attempt, but
      were least likely to have a recorded mental health or substance use diagnosis.
      Overall, visits were most common in primary care and outpatient general medical
      settings. CONCLUSIONS: This study provides temporal evidence of racial/ethnic
      differences in health care visits made before suicide attempt. Health care
      systems can use this information to help focus the design and implementation of
      their suicide prevention initiatives.

PMID- 25872152
TI  - Directed molecular assembly into a biocompatible photosensitizing nanocomplex for
      locoregional photodynamic therapy.
AB  - Methylene blue (MB), a water-soluble cationic dye widely used in the clinic, is
      known to photosensitize the generation of cytotoxic singlet oxygen efficiently,
      and thus, has attracted interest as a potential drug for photodynamic therapy
      (PDT). However, its use for the in vivo PDT of cancer has been limited due to the
      inherently poor cell/tissue accumulation and low biological stability in the free
      molecular form. Here, we report a simple and biocompatible nanocomplex
      formulation of MB (NanoMB) that is useful for in vivo locoregional cancer
      treatment by PDT. NanoMB particles were constructed through the self-assembly of
      clinically usable molecules (MB, fatty acid and a clinically approved polymer
      surfactant) directed by the dual (electrostatic and hydrophobic) interactions
      between the ternary constituents. The nanocomplexed MB showed greatly enhanced
      cell internalization while keeping the photosensitization efficiency as high as
      free MB, leading to distinctive phototoxicity toward cancer cells. When
      administered to human breast cancer xenograft mice by peritumoral injection,
      NanoMB was capable of facile penetration into the tumor followed by cancer cell
      accumulation, as examined in vivo and histologically with the near-infrared
      fluorescence signal of MB. The quintuple PDT treatment by a combination of
      peritumorally injected NanoMB and selective laser irradiation suppressed the
      tumor volume efficaciously, demonstrating potential of NanoMB-based PDT as a
      biocompatible and safe method for adjuvant locoregional cancer treatment. 

PMID- 25872153
TI  - The Effect of Sphingosine 1-Phosphate/Sphingosine 1-Phosphate Receptor on
      Neutrophil Function and the Relevant Signaling Pathway.
AB  - BACKGROUND/AIMS: This study investigated the priming effect of sphingosine 1
      phosphate (S1P) on formyl-Met-Leu-Phe-OH (fMLP)-activated neutrophils, by
      specific analysis of the neutrophil respiratory burst and the signaling pathway
      involved in S1P activity. METHODS: The neutrophil respiratory burst was
      indirectly detected by the cytochrome c reduction method and the dihydrorhodamine
      123 staining method. The signal transduction pathways of neutrophil respiratory
      burst primed by S1P were detected by Western blotting. RESULTS: Our results
      showed that the S1P receptors (S1PRs) 1, 4 and 5 were the predominantly expressed
      neutrophil S1PRs at the cDNA level. After pretreatment with S1P, the fMLP
      activated neutrophils released increased levels of superoxide anions. PI3K and
      Akt proteins were involved in the signaling pathway of the neutrophil respiratory
      burst primed by S1P. CONCLUSION: The results indicate that S1P is a new priming
      reagent for neutrophils and primes the respiratory burst of fMLP-activated
      neutrophils. S1P interacts with its receptors on neutrophils, resulting in NADPH
      oxidase activation by the PI3K-Akt cell signaling pathway and induction of the
      neutrophil respiratory burst.

PMID- 25872155
TI  - Direct access to functionalized benzotropones, azepanes, and piperidines by
      reductive cross-coupling of alpha-bromo enones with alpha-bromo enamides.
AB  - The synthesis of functionalized azepenes and piperidines bearing an alpha
      cycloheptenone or benzotropone derivative has been accomplished through direct
      reductive cross-coupling of alpha-bromo eneformamides or enecarbamates with
      highly versatile alpha-bromo benzotropone derivatives, under cobalt catalysis.
      The coupling products have been further elaborated to other synthetically useful
      aza-heterocyclic frameworks. 

PMID- 25872156
TI  - Exercise reward induces appetitive 50-kHz calls in rats.
AB  - Rats express affective states by visible behaviors (like approach or flight) and
      through different kinds of ultrasonic vocalizations (USV). 50-kHz calls are
      thought to reflect positive affective states since they occur during rewarding
      situations like social play or palatable food. However, the effects of voluntary
      exercise on USV have not been investigated yet, although such exercise can serve
      as reward. To this aim, we gave young adult rats restricted daily access to a
      runway maze, where they could interact with either a movable (experimental group)
      or locked wheel (sedentary group) for 14days and we tested USV in anticipation of
      and during subsequent running. We also studied inter-individual differences in
      running, and relationships with USV, and rat-typical trait measures. The results
      showed that the experimental rats had to be separated into "runners" and
      "pseudorunners" since only runners performed true running, whereas pseudorunners
      hardly entered the wheel and turned it only with their forelimbs. This outcome
      seems to be related to subject-dependent differences in responding to novelty and
      in reward sensitivity, as indicated by pertinent screening tests, which we had
      performed prior to the 14days of wheel access. In the runway, our experimental
      and control groups did not differ in visible anticipatory behavior, like
      approach. Yet, only runners and sedentary rats displayed an increasing but
      similar amount of anticipatory USV, which is suggestive of a state of incentive
      anticipation of the coming wheel access. During exercise, only runners increased
      USV, probably indicating a highly positive emotional state. To conclude,
      voluntary exercise provides a promising tool to induce 50-kHz USV during and in
      anticipation of exercise. When performing such studies, possible individual
      differences between subjects have to be taken into account, and the actual wheel
      performance should carefully be controlled. 

PMID- 25872157
TI  - Flexible suspended gate organic thin-film transistors for ultra-sensitive
      pressure detection.
AB  - The utilization of organic devices as pressure-sensing elements in artificial
      intelligence and healthcare applications represents a fascinating opportunity for
      the next-generation electronic products. To satisfy the critical requirements of
      these promising applications, the low-cost construction of large-area ultra
      sensitive organic pressure devices with outstanding flexibility is highly
      desired. Here we present flexible suspended gate organic thin-film transistors
      (SGOTFTs) as a model platform that enables ultra-sensitive pressure detection.
      More importantly, the unique device geometry of SGOTFTs allows the fine-tuning of
      their sensitivity by the suspended gate. An unprecedented sensitivity of 192 kPa(
      1), a low limit-of-detection pressure of <0.5 Pa and a short response time of 10
      ms were successfully realized, allowing the real-time detection of acoustic
      waves. These excellent sensing properties of SGOTFTs, together with their
      advantages of facile large-area fabrication and versatility in detecting various
      pressure signals, make SGOTFTs a powerful strategy for spatial pressure mapping
      in practical applications. 

PMID- 25872158
TI  - The Non-carcinogenic Risk of Cadmium in Bottled Water in Different Age Groups
      Humans: Bandar Abbas City, Iran.
AB  - INTRODUCTION: The presence of heavy metals such as cadmium in drinking water
      resources can be dangerous for human because of toxicity and biological
      accumulation. The consumption of water which contains Cd in high concentration
      can lead to Bone and Kidney diseases. MATERIAL AND METHODS: In this present
      study, the researcher collected 432 samples of bottled water in the popular marks
      in summer and winter from the surface of Bandar Abbas. The cadmium concentration
      was measured by atomic absorption Spectrophotometer in model DR2800 through the
      Dithizone method. CDI, R and HQ which are caused by Cd for adult men, women and
      children, have been calculated and evaluated through the equations of EPA and
      WHO. RESULTS: Mean of 1.73+/-0.19 ug/l (M+/-SE) is lower than the standard of WHO
      and EPA. However, 33.2% of all the samples have concentrations more than the
      standard limit of WHO, and the concentrations of 22.4% of the samples are more
      than EPA's standard. The CDI for different age groups is as following manner;
      Children>adult women>adult men. The CDI in children is more than twice as much as
      in the CDI for adult men and women. The mean of HQ order for different age groups
      is children>adult men>adult women. Since HQ of adult men (34E-5), adult women
      (31E-5) and children (84E-5), is lower than 1. CONCLUSION: It can be said that
      the population of Bandar Abbas is in a safe area regarding the HQ of the bottled
      water's cadmium.

PMID- 25872159
TI  - Advances and challenges in PBPK modeling--Analysis of factors contributing to the
      oral absorption of atazanavir, a poorly soluble weak base.
AB  - Many active pharmaceutical ingredients (APIs) exhibit a highly variable
      pharmacokinetic (PK) profile. This behavior may be attributable to pre
      absorptive, absorptive and/or post-absorptive factors. Pre-absorptive factors are
      those related to dosage form disintegration, drug dissolution, supersaturation,
      precipitation and gastric emptying. Absorptive factors are involved with drug
      absorption and efflux mechanisms, while drug distribution and clearance are post
      absorptive factors. This study aimed to investigate the relative influence of the
      aforementioned parameters on the pharmacokinetic profile of atazanavir, a poorly
      soluble weakly basic compound with highly variable pharmacokinetics. The pre
      absorptive behavior of the drug was examined by applying biorelevant in vitro
      tests to reflect upper gastrointestinal behavior in the fasted and fed states.
      The in vitro results were implemented, along with permeability and post
      absorptive data obtained from the literature, into physiologically based
      pharmacokinetic (PBPK) models. Sensitivity analysis of the resulting plasma
      profiles revealed that the pharmacokinetic profile of atazanavir is affected by
      an array of factors rather than one standout factor. According to the in silico
      model, pre-absorptive and absorptive factors had less impact on atazanavir
      bioavailability compared to post-absorptive parameters, although active drug
      efflux and extraction appear to account for the sub-proportional pharmacokinetic
      response to lower atazanavir doses in the fasted state. From the PBPK models it
      was concluded that further enhancement of the formulation would bring little
      improvement in the pharmacokinetic response to atazanavir. This approach may
      prove useful in assessing the potential benefits of formulation enhancement of
      other existing drug products on the market. 

PMID- 25872160
TI  - Effect of carvedilol against myocardial injury due to ischemia-reperfusion of the
      brain in rats.
AB  - We have previously reported the mechanism behind the myocardial injury and the
      activation of autonomic nervous system during the ischemia-reperfusion (IR) of
      the rat brain. This study was planned to investigate the effect of carvedilol, a
      beta-blocker, in improving the myocardial injury caused by IR of the rat brain.
      We have used a whole cerebral IR model in rats by clamping both the right and
      left common carotid arteries. Rats were divided into five groups; Sham surgery
      group (Group-Sham), carvedilol treatment before ischemia group (Group-Is+C),
      vehicle control group (Group-Is+V), carvedilol treatment before reperfusion group
      (Group-Re+C) and the vehicle control group (Group-Re+V). We have measured the
      blood pressure and heart rate via a catheter, myocardial tissue beta1-adrenaline
      receptor (beta1-AR) levels, phosphor-p38 mitogen-activated protein kinase (p-p38
      MAPK) signaling factor, malondialdehyde (MDA), and apoptosis (TUNEL assay and
      expression of caspase-7 protein). The results indicated that the increased
      expressions of beta1-AR, p-p38 MAPK, caspase-7, apoptotic cells and MDA level in
      the myocardial tissue due to brain ischemia-reperfusion were significantly
      reduced by carvedilol treatment. From these observations we can suggest that,
      with the advantage of its antioxidant and beta blocking action, carvedilol had
      played the improvement of myocardial injury in ischemia-reperfusion of the brain.

PMID- 25872161
TI  - Breastfeeding and Autism Spectrum Disorder in the National Survey of Children's
      Health.
AB  - BACKGROUND: Breastfeeding is thought to promote healthy cognitive development. A
      small number of studies have also reported a protective association between
      breastfeeding and autism spectrum disorder (ASD). The National Survey of
      Children's Health (2007, 2011), a large nationally representative survey of US
      children, was examined to determine whether breastfeeding of infants is
      associated with later development of ASD. METHODS: Respondents with a child ages
      2-5 years (n = 37,901) were queried about whether their child was currently
      diagnosed with ASD and about their child's breastfeeding history. Additional
      information was available about child and family health history and family
      demographics. Survey-weighted logistic regressions were employed to examine ASD
      diagnosis as associated with several breastfeeding exposure metrics including a
      history of partial or exclusive breastfeeding for the first 3 or 6 months, and
      duration of partial or exclusive breastfeeding. RESULTS: Across models, a current
      diagnosis of ASD (n = 391) was unassociated with any measure of breastfeeding
      history. Adjusted odds ratios for categorical breastfeeding exposures ranged from
      0.68 (confidence interval [CI] = 0.4, 1.3) for any partial breastfeeding to 0.74
      (CI = 0.3, 1.7) for 6 months of exclusive breastfeeding. When exposure was
      measured continuously, adjusted odds ratios were 1.03 (CI = 0.97, 1.10) for each
      additional month of partial breastfeeding and 1.04 (CI = 0.96, 1.13) for each
      additional month of exclusive breastfeeding. CONCLUSION: These findings call into
      question the results from the small body of research that has examined this issue
      to date.

PMID- 25872162
TI  - Simulation Comparison of the Quality Effects and Random Effects Methods of Meta
      analysis.

PMID- 25872163
TI  - Sex differences in the role of NADPH oxidases in endothelium-dependent
      vasorelaxation in porcine isolated coronary arteries.
AB  - The present study examined whether vascular function, expression and activity of
      NADPH oxidases differ between sexes in porcine isolated coronary arteries (PCAs)
      using selective Nox inhibitors, ML-171 and VAS2870. Vascular responses of distal
      PCAs were examined under myographic conditions in the presence of a range of
      inhibitors. Nox activity in PCA homogenates was assessed using lucigenin-enhanced
      chemiluminescence. Protein expression of Nox1, Nox2 and Nox4 was compared using
      Western immunoblotting. The presence of ML-171 or DPI had no effect on the
      bradykinin-induced vasorelaxation in PCAs from females. In males, DPI shifted the
      EC50 2.8-fold to the right. In the presence of L-NAME and indomethacin, DPI and
      ML-171 had no effect in females, but enhanced the bradykinin-induced
      vasorelaxation in males. ML-171 had no effect on the forskolin-induced
      vasorelaxation but decreased the potency of U46619-induced tone in both sexes in
      the absence or presence of endothelium. VAS2870 had no effect on the bradykinin
      induced vasorelaxation in both sexes but reduces the EDH-type response in males
      only. Nox activity was reduced by DPI and ML-171, but not VAS2870 in PCAs from
      both sexes. Protein expression of Nox1 and Nox2 in PCAs was higher in males
      compared to females whereas Nox4 was higher in females. Inhibition of Nox with ML
      171 enhances while VAS2870 reduces the EDH-type response in PCAs from males but
      not females. This indicates that Nox-generated ROS play a role in the EDH-type
      response in males with differences attributed to the differential expression of
      Nox isoforms. This may underlie the greater oxidative stress observed in males. 

PMID- 25872164
TI  - Angiotensin type 1 receptor mediates chronic ethanol consumption-induced
      hypertension and vascular oxidative stress.
AB  - OBJECTIVES: We hypothesized that chronic ethanol intake enhances vascular
      oxidative stress and induces hypertension through renin-angiotensin system (RAS)
      activation. METHODS AND RESULTS: Male Wistar rats were treated with ethanol (20%
      v/v). The increase in blood pressure induced by ethanol was prevented by losartan
      (10mg/kg/day; p.o. gavage), a selective AT1 receptor antagonist. Chronic ethanol
      intake increased plasma renin activity (PRA), angiotensin converting enzyme (ACE)
      activity, plasma angiotensin I (ANG I) and angiotensin II (ANG II) levels and
      serum aldosterone levels. No differences on plasma osmolality and sodium or
      potassium levels were detected after treatment with ethanol. Ethanol consumption
      did not alter ACE activity, as well as the levels of ANG I and ANG II in the rat
      aorta or mesenteric arterial bed (MAB). Ethanol induced systemic and vascular
      oxidative stress (aorta and MAB) and these effects were prevented by losartan.
      The decrease on plasma and vascular nitrate/nitrite (NOx) levels induced by
      ethanol was prevented by losartan. Ethanol intake did not alter protein
      expression of ACE, AT1 or AT2 receptors in both aorta and MAB. Aortas from
      ethanol-treated rats displayed decreased ERK1/2 phosphorylation and increased
      protein expression of SAPK/JNK. These responses were prevented by losartan. MAB
      from ethanol-treated rats displayed reduced phosphorylation of p38MAPK and ERK1/2
      and losartan did not prevent these responses. CONCLUSIONS: Our study provides
      novel evidence that chronic ethanol intake increases blood pressure, induces
      vascular oxidative stress and decreases nitric oxide (NO) bioavailability through
      AT1-dependent mechanisms.

PMID- 25872165
TI  - Development and validation of a new assay for assessing clot integrity.
AB  - INTRODUCTION: Research and routine laboratory assessment of clot integrity can be
      time consuming, expensive, and cannot be batched as it is generally performed in
      real time. To address these issues, we developed and validated a micro-titre
      based assay to quantify thrombogenesis and fibrinolysis, the purpose being to
      assess patients at risk of cardiovascular events by virtue of hypercoagulability.
      In further validation, thrombogenesis results were compared to similar indices
      from the thrombelastograph (TEG). METHODS: Our assay determines three indices of
      thrombogenesis (lag time to the start of thrombus formation (LT), rate of clot
      formation (RCF), and maximum clot density (MCD)) and two of fibrinolysis (rate of
      clot dissolution (RCD) and time for 50% of the clot to lyse (T50)). Plasma was
      tested fresh and again after being frozen at -70 degrees C. Some samples were
      tested immediately, others after being left at room temperature for up to 24h.
      RESULTS: The intra-assay coefficients of variation (CVs) of the three
      thrombogenesis measures (LT, RCF, MCD) and two fibrinolysis measures (RCD, T50)
      varied between 2.7 and 12.0% in fresh plasma and between 1.3% and 10.8% in frozen
      plasma respectively. Similarly, the inter-assay coefficients of variation of the
      thrombogenesis and fibrinolysis measures were 4.9-10.8% in fresh plasma and 2.2
      6.5% in frozen plasma respectively. TEG assays intra- and inter assay CVs were
      around 25%. There were no significant differences in all plate assay indices up
      to 6h at room temperature. Certain plate assay thrombogenesis data were
      comparable to TEG indices after analysis by Pearson's correlation. The reagent
      processing cost per sample is L15 for TEG and L2 for the plate assays.
      CONCLUSION: Our micro-titre based assay assessing plasma thrombogenesis and
      fibrinolysis has good intra- and inter-assay CVs, can assess plasma up to 6h
      after venepuncture, is more efficient (in terms of throughput) and is more
      economical than that of the TEG.

PMID- 25872166
TI  - Severe acute kidney injury associated with non-steroidal anti-inflammatory drugs
      in cirrhosis: A case-control study.
AB  - BACKGROUND & AIMS: Non-steroidal anti-inflammatory drugs (NSAIDs) may cause
      impairment of kidney function in patients with cirrhosis. Investigational studies
      demonstrated reversibility of kidney dysfunction after drug withdrawal, but
      information based on clinical practice is lacking. The aim of the study was to
      investigate the characteristics and outcome of Acute Kidney Injury (AKI)
      developing in patients with cirrhosis treated with NSAIDs. METHODS: Prospective
      cohort study in a tertiary referral center of all patients with NSAIDs-associated
      AKI seen from 2002 to 2014. For comparison, three control groups of patients with
      hypovolemic-induced AKI, type-1 HRS and ATN, respectively, were also evaluated.
      Urinary excretion of neutrophil gelatinase-associated lipocalin (uNGAL) was
      measured in a subset of patients. RESULTS: Thirty patients with cirrhosis and
      NSAIDs-associated AKI were identified. In 19 patients (63%) AKI was transient and
      kidney function rapidly recovered (4+/-3 days) after NSAIDs withdrawal. In the
      remaining 11 patients (37%) AKI was more severe and persisted during
      hospitalization despite drug withdrawal. Patients with persistent AKI had
      remarkably higher uNGAL levels compared with those of patients with transient AKI
      (953+/-1,198 vs. 83+/-79 MUg/g of creatinine, respectively, p=0.008). Moreover,
      seven of the 11 patients with persistent AKI (64%) died within three months
      compared with only one of the 19 (5%) patients with transient AKI (p=0.001).
      Mortality of persistent AKI was similar in NSAIDs patients compared to control
      groups. The only independent predictive factor of three-month mortality was
      persistent AKI. CONCLUSIONS: Patients with cirrhosis treated with NSAIDs may
      develop severe AKI which may be irreversible and associated with poor short-term
      outcome.

PMID- 25872167
TI  - Laparoscopic versus open liver resection for hepatocellular carcinoma: Case
      matched study with propensity score matching.
AB  - BACKGROUND & AIMS: Laparoscopic liver resection has gained wide acceptance and is
      established as a safe alternative to open liver resection. Until now, there is no
      prospective randomized comparative study between laparoscopic and open liver
      resection. Previous comparative studies reported minor resections for peripheral
      tumors, and enrolled small numbers of patients. Moreover, few reported the long
      term outcomes. The aim of this study is to compare perioperative and long term
      outcomes of laparoscopic versus open liver resection for hepatocellular carcinoma
      between two matched groups. METHODS: 389 patients underwent liver resection for
      hepatocellular carcinoma during the period between 2004 and 2013. To overcome
      selection bias, we performed 1:1 match using propensity score matching between
      laparoscopic and open liver resection. RESULTS: After propensity score matching,
      88 patients were included in each group. Laparoscopic group had shorter hospital
      stay (8 vs. 10 days, p?0.001), and lower postoperative morbidity (12.5% vs.
      20.4%, p=0.042). The 1-, 3- and 5-year overall survivals were 91.6%, 87.5%, and
      76.4%, for laparoscopic group, and were 93.1%, 87.8%, and 73.2%, for open group
      (p=0.944). The 1-, 3- and 5-year disease free survivals were 69.7%, 52%, and
      44.2%, for laparoscopic group, and 74.7%, 49.5%, 41.2%, for open group (p=0.944).
      CONCLUSIONS: Our study showed comparative perioperative and long term outcomes
      between both groups, providing evidence regarding the safety and efficacy of
      laparoscopic liver resection for hepatocellular carcinoma.

PMID- 25872168
TI  - Hepatic cell proliferation plays a pivotal role in the prognosis of alcoholic
      hepatitis.
AB  - BACKGROUND & AIMS: The role of liver progenitor cell (LPC) expansion, known as a
      marker of disease severity, as well as the impact of macrophage activation on
      liver regeneration remains unclear in humans. We aimed to characterize the LPC
      and macrophage compartments in alcoholic hepatitis (AH), as well as gene
      expression patterns to identify predictors of a good prognosis in this setting.
      METHODS: Immunohistochemical studies for macrophages, proliferative hepatocytes,
      total and proliferative LPC, as well as whole liver microarray gene expression
      were performed on baseline liver biopsies of 58 AH patients early after
      admission. Abstinent cirrhotic patients were used as controls. Patients were
      qualified as "improvers" or "non-improvers" based on the change in MELD score
      three months after baseline. RESULTS: Compared to controls, AH patients
      demonstrated a significant expansion of macrophages, invasion of LPC and a higher
      number of proliferating hepatocytes and LPC. In AH patients, total LPC expansion
      (total Keratin7(+) cells) was associated with liver disease severity. The group
      of improvers (n=34) was characterized at baseline by a higher number of
      proliferating hepatocytes, proliferative LPC (double Keratin7(+)Ki67(+) cells)
      and liver macrophages as compared to non-improvers (n=24), despite similar
      clinical and biological variables. Upregulated genes in improvers were associated
      with cell cycle mitosis together with a major expression of SPINK1. CONCLUSIONS:
      Higher liver macrophage expansion, increased proliferative hepatocyte but also
      LPC number, as well as an upregulation of cell proliferation-related genes are
      associated with a favourable outcome. These new findings open novel therapeutic
      targets in AH.

PMID- 25872169
TI  - A THz/FTIR fingerprint of the solvated proton: evidence for Eigen structure and
      Zundel dynamics.
AB  - In continuation of earlier work on La(III), Ni(II) and Mn(II) halides, we present
      low frequency (30-400 cm(-1)) spectra of solvated HCl and HBr as a function of
      solute concentration. This frequency range provides direct access to water
      network modes and changes induced by solvated solutes. We were able to dissect
      the spectra into components associated to solvated ions and ion pairs using a
      chemical equilibrium model in combination with principal component analysis.
      While the Cl(-) rattling mode at 190 cm(-1) is found to be unchanged, the Br(-)
      resonance around 90 cm(-1) is decreased in intensity below the detection
      threshold when replacing the divalent or trivalent metal ions by a proton. The
      solvated proton shows two resonances: a solvation water mode around 140 cm(-1)
      and a high frequency resonance at 325 cm(-1) that we assign to the rattling
      motion of an Eigen structure H3O(+) in its solvation cage. This assignment is
      corroborated by isotopic substitution measurements which show a redshift of the
      high frequency peak when HCl/H2O is replaced by DCl/D2O. The linewidth of the
      H3O(+) rattling mode corresponds to a relaxation time of the oscillatory process
      of tau ~ 60 fs, considerably faster than the relaxation time of tau ~ 160 fs for
      Cl(-). In addition, we find a broad background that we attribute to fast non
      oscillatory motions of a proton in a Zundel-like complex. Our results are in
      agreement with an Eigen-Zundel-Eigen (EZE) model of proton transport. Upon ion
      pairing the broad background is strongly reduced indicating a reduction of fast
      proton transfer processes. The Cl(-) resonance blueshifts by 20 cm(-1) which
      indicates a transition from free ions to a solvent shared ion pair. Surprisingly,
      the center frequency of the Eigen complex does not change upon ion pairing. This
      can be rationalized in terms of an unchanged local solvation structure.

PMID- 25872170
TI  - Risk factors for the development of intra-abdominal fungal infections in acute
      pancreatitis.
AB  - OBJECTIVES: Intra-abdominal fungal infections (AFIs) complicating acute
      pancreatitis arise in the context of pancreatic necrosis. Our goal was to
      determine which risk factors contribute to AFI in patients with acute
      pancreatitis. METHODS: Records were reviewed from 479 nontransfer patients
      admitted to our medical center with acute pancreatitis from 1985 to 2009. Using
      multivariable regression models, we identified risk factors for AFI. RESULTS: Of
      479 patients admitted with acute pancreatitis, 17 patients were subsequently
      found to have an AFI and 3 of these patients died. The mean length of stay for
      patients with an AFI was 24 days, and 76% were admitted to the intensive care
      unit. The patients with AFI were more likely to have received prophylactic
      antibiotics on admission (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.2
      2.3) and total parenteral nutrition within 7 days of admission (OR, 1.4; 95% CI,
      1.1-1.7) or to have necrosis on CT scan within 7 days of admission (OR, 1.4; 95%
      CI, 1.1-1.7). Multivariable regression models identified admission antibiotic use
      (OR, 1.6; 95% CI, 1.4-1.8) as the strongest predictor of AFI. CONCLUSIONS:
      Admission antibiotics are the biggest risk factor for the development of intra
      AFIs in acute pancreatitis. Prophylactic antibiotics to prevent infected necrosis
      should therefore be discouraged.

PMID- 25872171
TI  - The effect of lornoxicam on TLR2 and TLR4 messenger RNA expression and tumor
      necrosis factor-alpha, interleukin-6, and interleukin-8 secretion in patients
      with systemic complications of acute pancreatitis.
AB  - OBJECTIVES: To assess the effects of the cyclooxygenase-1/cyclooxygenase-2
      inhibitor lornoxicam on systemic complications in patients with acute
      pancreatitis, Toll-like receptor (TLR)2 and TLR4 messenger RNA expression, and
      cytokine secretion (IL-6, IL-8, tumor necrosis factor-alpha). METHODS: Adult
      patients with acute pancreatitis were randomized to standard therapy or standard
      therapy plus lornoxicam. Standard therapy included analgesics, spasmolytics,
      octreotide, pantoprazole, and intravenous fluids. The TLR2 and TLR4 expression
      levels and TLR2- and TLR4-mediated cytokine production in peripheral blood
      mononuclear cells were assessed in patients with severe complications and in
      healthy volunteers (n = 15). RESULTS: A total of 334 patients received standard
      therapy (n = 246) or standard therapy plus lornoxicam (n = 88), 172 (51.5%) of
      whom developed systemic complications. Occurrence of complications was higher
      with standard therapy compared with lornoxicam (57.3% versus 35.2%; P = 0.00034),
      as was mortality (19.1% versus 6.8%; P = 0.006). The TLR2 and TLR4 expression and
      TLR2 and TLR4-mediated cytokine production were significantly higher in patients
      with systemic complications of acute pancreatitis compared with healthy
      volunteers. Relative TLR2 expression and cytokine production were significantly
      reduced in patients receiving lornoxicam versus standard therapy. CONCLUSIONS:
      The use of lornoxicam at the onset of acute pancreatitis decreased TLR2 and TLR4
      expression and the production of proinflammatory cytokines, thereby reducing the
      risk of systemic complications and mortality.

PMID- 25872172
TI  - Outcomes of systematic nutritional assessment and medical nutrition therapy in
      pancreatic cancer.
AB  - OBJECTIVES: We investigated the nutritional and survival outcomes of medical
      nutrition therapy by a registered dietitian, along with support from a dedicated
      nutrition and metabolic support team in pancreatic cancer patients requiring
      enteral or parenteral nutrition. METHODS: Subjective global assessment (SGA) was
      used to assess nutritional status in 304 pancreatic cancer patients. Using
      baseline and last SGA, patients were categorized into 3 groups: improved SGA,
      deteriorated SGA, and unchanged SGA. Kaplan-Meier and Cox regression were used to
      calculate survival after controlling for relevant confounders. RESULTS: One
      hundred twenty-five (41.1%) patients had their SGA unchanged, 87 (28.6%) patients
      had "improved SGA," whereas 92 (30.3%) patients had "deteriorated SGA." On
      univariate survival analysis, the median survival was 7.8, 11.2, and 12.6 months
      for deteriorated, unchanged, and improved SGA groups, respectively. On
      multivariate analysis, change in SGA was independently predictive of survival.
      Patients with deteriorated SGA had 1.5 times (95% confidence interval, 1.1-2.1)
      greater risk of mortality compared to those with improved SGA. CONCLUSIONS: The
      majority of pancreatic cancer patients (70%) in our study either maintained or
      improved their nutritional status during cancer treatment. Improvement in SGA
      correlated with a significantly decreased risk of mortality independent of sex,
      previous treatment history, and evidence of biological anticancer activity.

PMID- 25872173
TI  - Laparoscopic and Percutaneous Core Needle Biopsy Plays a Central Role for the
      Diagnosis of Autoimmune Pancreatitis in a Single-Center Study From Denmark.
AB  - OBJECTIVES: The aims of this study were to describe the diagnosis of autoimmune
      pancreatitis (AIP) in Denmark and to test the usefulness of the International
      Consensus Diagnostic Criteria (ICDC) on a geographically well-defined cohort.
      METHODS: All patients diagnosed with AIP at Odense University Hospital from 2007
      to 2013 were included (n = 30; mean follow-up, 26.2 months). Data from
      laparoscopic or percutaneous ultrasound-guided core needle biopsy (CNB),
      resection specimens, endoscopic ultrasound (EUS), EUS-guided CNB, computed
      tomography, serum immunoglobulin G4 (IgG4), and pancreatography were
      retrospectively analyzed according to ICDC. RESULTS: Twenty patients were
      diagnosed with type 1, 8 with type 2, and 2 with not otherwise specified AIP.
      Twenty-eight patients (93%) could correctly be classified when ICDC were
      retrospectively applied. Serum IgG4 was elevated in 44% of type 1 and 0% of type
      2. Other organ involvement was observed in 40% of type 1 and 13% of type 2, but
      inflammatory bowel disease only in type 2 (P = 0.001). One patient had IgG4
      related chronic perisplenitis as a hitherto undescribed manifestation of IgG4
      related disease. Nineteen (91%) of 21 biopsied patients had diagnostic CNB
      features of AIP. Computed tomography, EUS, and pancreatography showed features
      highly suggestive or supportive of AIP in 68%, 72%, and 71%, respectively.
      CONCLUSIONS: Laparoscopic or percutaneous ultrasound-guided CNB had the highest
      sensitivity for AIP. The ICDC could retrospectively correctly diagnose 93% of the
      patients.

PMID- 25872174
TI  - Biomechanical factors may explain why grasping violates Weber's law.
AB  - For grasping, Ganel, Chajut, and Algom (2008) demonstrated that the variability
      of the maximum grip aperture (MGA) does not increase with the size of the target
      object. This seems to violate Weber's law, a fundamental law of psychophysics.
      They concluded that the visual representations guiding grasping are distinct from
      representations used for perceptual judgments. Weber's law is however only
      relevant for one component of the measurable variability of MGA, namely the
      variability in the sensory system. We argue that when looking at the relationship
      between object size and grasping, the gain (often called slope) governing the
      relationship between target size and MGA can be used as an approximation to
      estimate the contribution of sensory noise to MGA variability. To test the idea
      that differences in gain modulate the relationship between target size and MGA
      variability, we examined grasping under a variety of conditions. We found that
      gain varied quite significantly across different tasks, but irrespective of gain
      Weber's law could not be found in any of the grasping tasks. Instead we
      repeatedly found an inverse relationship between variability and object size,
      i.e. variability decreased for bigger objects. This trend may reflect the reduced
      biomechanical freedom found for movements at the end an effector's effective
      range of motion. MGA variability may thus be dominated by non-sensory factors and
      therefore may constitute a poor choice to estimate the variability of the visual
      signals used by the brain to guide our grasping actions. 

PMID- 25872175
TI  - Investigating photoreceptor densities, potential visual acuity, and cone mosaics
      of shallow water, temperate fish species.
AB  - The eye is an important sense organ for teleost species but can vary greatly
      depending on the adaption to the habitat, environment during ontogeny and
      developmental stage of the fish. The eye and retinal morphology of eight commonly
      caught trawl bycatch species were described: Lepidotrigla mulhalli; Lophonectes
      gallus; Platycephalus bassensis; Sillago flindersi; Neoplatycephalus richardsoni;
      Thamnaconus degeni; Parequula melbournensis; and Trachurus declivis. The cone
      densities ranged from 38 cones per 0.01 mm(2) for S. flindersi to 235 cones per
      0.01 mm(2) for P. melbournensis. The rod densities ranged from 22800 cells per
      0.01 mm(2) for L. mulhalli to 76634 cells per 0.01 mm(2) for T. declivis and
      potential visual acuity (based on anatomical measures) ranged from 0.08 in L.
      gallus to 0.31 in P. melbournensis. Higher rod densities were correlated with
      maximum habitat depths. Six species had the regular pattern of four double cones
      arranged around a single cone in the photoreceptor mosaic, while T. declivis had
      only rows of double cones. P. melbournensis had the greatest potential ability
      for detecting fine detail based on eye anatomy. The potential visual acuity
      estimates and rod densities can be applied to suggest the relative detection
      ability of different species in a commercial fishing context, since vision is a
      critical sense in an illuminated environment for perceiving an oncoming trawl.

PMID- 25872176
TI  - Using the past to anticipate the future in human foraging behavior.
AB  - Humans engage in many tasks that involve gathering multiple targets from their
      environment (e.g., picking berries from a patch). Such foraging tasks raise
      questions about how observers maximize target collection - e.g., how long should
      one spend at one berry patch before moving to the next patch. Classic optimal
      foraging theories propose a simple decision rule: People move on when current
      intake drops below the average rate. Previous studies of foraging often assume
      this average is fixed and predict no strong relationship between the contents of
      the immediately preceding patch or patches and the current patch. In contrast to
      this prediction, we found evidence of temporal effects in a laboratory analog of
      a berry-picking task. Observers stayed longer when previous patches were better.
      This result is the opposite of what would be predicted by a model in which the
      assessment of the average rate is biased in favor of recent patches. This result
      was found when patch quality varied systematically over the course of the
      experiment (Experiment 1). Smaller effects were seen when patch quality was
      randomized (Experiment 2). Together, these results suggest that optimal foraging
      theories must account for the recent history to explain current behavior. 

PMID- 25872178
TI  - Preference for luminance histogram regularities in natural scenes.
AB  - Natural scene luminance distributions typically have positive skew, and for
      single objects, there is evidence that higher skew is a correlate (but not a
      guarantee) of glossiness. Skewness is also relevant to aesthetics: preference for
      glossy single objects (with high skew) has been shown even in infants, and
      skewness is a good predictor of fruit freshness. Given that primate vision
      appears to efficiently encode natural scene luminance variation, and given
      evidence that natural scene regularities may be a prerequisite for aesthetic
      perception in the spatial domain, here we ask whether humans in general prefer
      natural scenes with more positively skewed luminance distributions. If humans
      generally prefer images with the higher-order regularities typical of natural
      scenes and/or shiny objects, we would expect this to be the case. By manipulating
      luminance distribution skewness (holding mean and variance constant) for
      individual natural images, we show that in fact preference varies inversely with
      increasing positive skewness. This finding holds for: artistic landscape images
      and calibrated natural scenes; scenes with and without glossy surfaces; landscape
      scenes and close-up objects; and noise images with natural luminance histograms.
      Across conditions, humans prefer images with skew near zero over higher skew
      images, and they prefer skew lower than that of the unmodified scenes. These
      results suggest that humans prefer images with luminances that are distributed
      relatively evenly about the mean luminance, i.e., images with similar amounts of
      light and dark. We propose that our results reflect an efficient processing
      advantage of low-skew images over high-skew images, following evidence from prior
      brain imaging results. 

PMID- 25872177
TI  - Spatial distortions in localization and midline estimation in hemianopia and
      normal vision.
AB  - Studies have shown that individuals with hemianopia tend to bisect a line toward
      their blind, contralesional visual field, termed the hemianopic line bisection
      error (HLBE). One theory proposes that the HLBE is a perceptual distortion
      resulting from expansion of the central region of visual space. If true,
      perceptual expansions of the central regions in the intact hemifield should also
      be present and observable across different tasks. We tested this hypothesis using
      a peripheral localization task to assess localization and midpoint estimation
      along the horizontal axis of the visual field. In this task, participants judged
      the location of a target dot presented inside a Goldmann perimeter relative to
      their perceived visual field boundary. In Experiment 1, we tested neurologically
      healthy participants on the peripheral localization task as well as a novel
      midpoint assessment task in which participants reported their perceived midpoint
      along the horizontal axis of their left and right visual fields. The results
      revealed consistency in individual biases across the two tasks. We then used the
      peripheral localization task to test whether two patients with hemianopia showed
      a selective expansion of central visual space. For these patients, three axes
      were tested: the spared temporal horizontal axis and the upper and lower vertical
      axes. The results support the notion that the HLBE is due to expansion of
      perceived space along the spared temporal axis. Together, the results of both
      experiments validate the use of these novel paradigms for exploring perceptual
      asymmetries in both healthy individuals and patients with visual field loss. 

PMID- 25872179
TI  - Adults with dyslexia can use cues to orient and constrain attention but have a
      smaller and weaker attention spotlight.
AB  - We report results from two experiments assessing distribution of attention and
      cue use in adults with dyslexia (AwD) and in a group of typically reading
      controls. Experiment 1 showed normal effects of cueing in AwD, with faster
      responses when probes were presented within a cued area and normal effects of
      eccentricity and stimulus onset asynchrony (SOA). In addition, AwD showed
      stronger benefits of a longer SOA when they had to move attention farther, and
      stronger effects of inclusion on the left, suggesting that cueing is particularly
      important in more difficult conditions. Experiment 2 tested the use of cues in a
      texture detection task involving a wider range of eccentricities and a shorter
      SOA. In this paradigm, focused attention at the central location is actually
      detrimental and cueing further reduces performance. Thus, if AwD have a more
      distributed attention, they should show a reduced performance drop at central
      locations and, if they do not use cues, they should show less negative effects of
      cueing. In contrast, AwD showed a larger drop and a positive effect of cueing.
      These results are better accounted for by a smaller and weaker spotlight of
      attention. Performance does not decrease at central locations because the
      attentional spotlight is already deployed with maximum intensity, which cannot be
      further enhanced at central locations. Instead, use of cueing helps to focus
      limited resources. Cues orient attention to the right area without enhancing it
      to the point where this is detrimental for texture detection. Implications for
      reading are discussed. 

PMID- 25872180
TI  - Modeling spatiotemporal boundary formation.
AB  - Spatiotemporal boundary formation (SBF) refers to perception of continuous
      contours, shape, and global motion from sequential transformations of widely
      separated surface elements. How such minimal information in SBF can produce whole
      forms and the nature of the computational processes involved remain mysterious.
      Formally, it has been shown that orientations and motion directions of local edge
      fragments can be recovered from small sets of element changes (Shipley & Kellman,
      (1997). Vision Research, 37, 1281-1293). Little experimental work has examined
      SBF in simple situations, however, and no model has been able to predict human
      SBF performance. We measured orientation discrimination thresholds in simple SBF
      displays for thin, oriented bars as a function of element density, number of
      element transformations, and frame duration. Thresholds decreased with increasing
      density and number of transformations, and increased with frame duration. An
      ideal observer model implemented to give trial-by-trial responses in the same
      orientation discrimination task exceeded human performance. In a second group of
      experiments, we measured human precision in detecting inputs to the model
      (spatial, temporal, and angular inter-element separation). A model that modified
      the ideal observer by added encoding imprecision for these parameters, directly
      obtained from Exp. 2, and that included two integration constraints obtained from
      previous research, closely fit human SBF data with no additional free parameters.
      These results provide the first empirical support for an early stage in shape
      formation in SBF based on the recovery of local edge fragments from
      spatiotemporally sparse element transformation events.

PMID- 25872181
TI  - Two mechanisms that determine the Barber-Pole Illusion.
AB  - In the Barber-Pole Illusion (BPI), a diagonally moving grating is perceived as
      moving vertically because of the narrow, vertical, rectangular shape of the
      aperture window through which it is viewed. This strong shape-motion interaction
      persists through a wide range of parametric variations in the shape of the
      window, the spatial and temporal frequencies of the moving grating, the contrast
      of the moving grating, complex variations in the composition of the grating and
      window shape, and the duration of viewing. It is widely believed that end-stop
      feature (third-order) motion computations determine the BPI, and that Fourier
      motion-energy (first-order) computations determine failures of the BPI. Here we
      show that the BPI is more complex: (1) In a wide variety of conditions, weak
      feature stimuli (extremely fast, low contrast gratings, 21.5 Hz, 4% contrast)
      that stimulate only the Fourier (first-order) motion system actually produce a
      slightly better BPI illusion than classical strong-feature gratings (2.75 Hz, 32%
      contrast). (2) Reverse-phi barber-pole stimuli are seen exclusively in the
      feature (third-order) BPI direction when presented at 2.75 Hz and exclusively in
      the opposite (Fourier, first-order) BPI direction at 21.5Hz, indicating that both
      the first- and the third-order systems can produce the BPI. (3) The BPI in barber
      poles with scalloped aperture boundaries is much weaker than in normal straight
      edge barber poles for 2.75 Hz stimuli but not in 21.5 Hz stimuli. CONCLUSIONS:
      Both first-order and third-order stimuli produce strong BPIs. In some stimuli,
      local Fourier motion-energy (first-order) produces the BPI via a subsequent
      motion-path-integration computation (Journal of Vision (2014) 14, 1--27); in
      other stimuli, the BPI is determined by various feature (third-order) motion
      inputs; in most stimuli, the BPI involves combinations of both. High temporal
      frequency, low-contrast stimuli favor the first-order motion-path-integration
      computation; low temporal frequency, high-contrast stimuli favor third-order
      motion computations.

PMID- 25872183
TI  - Mutual antagonism of the paired-type homeobox genes, vsx2 and dmbx1, regulates
      retinal progenitor cell cycle exit upstream of ccnd1 expression.
AB  - Understanding the mechanisms that regulate the transition between the
      proliferative and a post-mitotic state of retinal progenitor cells (RPCs) is key
      to advancing our knowledge of retinal growth and maturation. In the present study
      we determined that during zebrafish embryonic retinal neurogenesis, two paired
      type homeobox genes - vsx2 and dmbx1 - function in a mutually antagonistic
      manner. We demonstrate that vsx2 gene expression requires active Fgf signaling
      and that this in turn suppresses dmbx1 expression and maintains cells in an
      undifferentiated, proliferative RPC state. This vsx2-dependent RPC state can be
      prolonged cell-autonomously by knockdown of dmbx1, or it can be suppressed
      prematurely by the over-expression of dmbx1, which we show can inhibit vsx2
      expression and lead to precocious neuronal differentiation. dmbx1 loss of
      function also results in altered expression of canonical cell cycle genes, and in
      particular up-regulation of ccnd1, which correlates with our previous finding of
      a prolonged RPC cell cycle. By knocking down ccnd1 and dmbx1 simultaneously, we
      show that RPCs can overcome this phenotype to exit the cell cycle on time and
      differentiate normally into retinal neurons. Collectively, our data provide novel
      insight into the mechanism that enables RPCs to exit the cell cycle through a
      previously unrecognized antagonistic interaction of two paired-type homeobox
      genes that are central regulators of an Fgf-vsx2-dmbx1-ccnd1 signaling axis. 

PMID- 25872184
TI  - Spen is required for pigment cell survival during pupal development in
      Drosophila.
AB  - Apoptosis is required during development to eliminate superfluous cells and
      sculpt tissues; spatial and timed control of apoptosis ensures that the necessary
      number of cells is eliminated at a precise time in a given tissue. The
      elimination of supernumerary pigment or inter-ommatidial cells (IOCs) depends on
      cell-cell communication and is necessary for the formation of the honeycomb-like
      structure of the Drosophila eye. However, the mechanisms occurring during pupal
      development and controlling apoptosis of superfluous IOC in space and time remain
      unclear. Here, we found that split-ends (spen) is required for IOC survival at
      the time of removal of superfluous IOCs. Loss of spen function leads to abnormal
      removal of IOCs by apoptosis. We show that spen is required non-autonomously in
      cone cells for the survival of IOCs by positively regulating the Spitz/EGFR
      pathway. We propose that Spen is an important survival factor that ensures
      spatial control of the apoptotic wave that is necessary for the correct
      patterning and formation of the Drosophila eye. 

PMID- 25872185
TI  - Network-constrained forest for regularized classification of omics data.
AB  - Contemporary molecular biology deals with wide and heterogeneous sets of
      measurements to model and understand underlying biological processes including
      complex diseases. Machine learning provides a frequent approach to build such
      models. However, the models built solely from measured data often suffer from
      overfitting, as the sample size is typically much smaller than the number of
      measured features. In this paper, we propose a random forest-based classifier
      that reduces this overfitting with the aid of prior knowledge in the form of a
      feature interaction network. We illustrate the proposed method in the task of
      disease classification based on measured mRNA and miRNA profiles complemented by
      the interaction network composed of the miRNA-mRNA target relations and mRNA-mRNA
      interactions corresponding to the interactions between their encoded proteins. We
      demonstrate that the proposed network-constrained forest employs prior knowledge
      to increase learning bias and consequently to improve classification accuracy,
      stability and comprehensibility of the resulting model. The experiments are
      carried out in the domain of myelodysplastic syndrome that we are concerned about
      in the long term. We validate our approach in the public domain of ovarian
      carcinoma, with the same data form. We believe that the idea of a network
      constrained forest can straightforwardly be generalized towards arbitrary omics
      data with an available and non-trivial feature interaction network. The proposed
      method is publicly available in terms of miXGENE system
      (http://mixgene.felk.cvut.cz), the workflow that implements the myelodysplastic
      syndrome experiments is presented as a dedicated case study. 

PMID- 25872186
TI  - Early free access to hypertonic NaCl solution induces a long-term effect on
      drinking, brain cell activity and gene expression of adult rat offspring.
AB  - Exposure to an altered osmotic environment during a pre/postnatal period can
      differentially program the fluid intake and excretion pattern profile in a way
      that persists until adulthood. However, knowledge about the programming effects
      on the underlying brain neurochemical circuits of thirst and hydroelectrolyte
      balance, and its relation with behavioral outputs, is limited. We evaluated
      whether early voluntary intake of hypertonic NaCl solution may program adult
      offspring fluid balance, plasma vasopressin, neural activity, and brain
      vasopressin and angiotensinergic receptor type 1a (AT1a)-receptor gene
      expression. The manipulation (M) period covered dams from 1 week before
      conception until offspring turned 1-month-old. The experimental groups were (i)
      Free access to hypertonic NaCl solution (0.45 M NaCl), food (0.18% NaCl) and
      water [M-Na]; and (ii) Free access to food and water only [M-Ctrol]. Male
      offspring (2-month-old) were subjected to iv infusion (0.15 ml/min) of hypertonic
      (1.5M NaCl), isotonic (0.15M NaCl) or sham infusion during 20 min. Cumulative
      water intake (140 min) and drinking latency to the first lick were recorded from
      the start of the infusion. Our results indicate that, after systemic sodium
      overload, the M-Na group had increased water intake, and diminished neuronal
      activity (Fos-immunoreactivity) in the subfornical organ (SFO) and nucleus of the
      solitary tract. They also showed reduced relative vasopressin (AVP)-mRNA and AT1a
      mRNA expression at the supraoptic nucleus and SFO, respectively. The data
      indicate that the availability of a rich source of sodium during the
      pre/postnatal period induces a long-term effect on drinking, neural activity, and
      brain gene expression implicated in the control of hydroelectrolyte balance.

PMID- 25872182
TI  - Genetic control of morphogenesis in Dictyostelium.
AB  - Cells grow, move, expand, shrink and die in the process of generating the
      characteristic shapes of organisms. Although the structures generated during
      development of the social amoeba Dictyostelium discoideum look nothing like the
      structures seen in metazoan embryogenesis, some of the morphogenetic processes
      used in their making are surprisingly similar. Recent advances in understanding
      the molecular basis for directed cell migration, cell type specific sorting,
      differential adhesion, secretion of matrix components, pattern formation,
      regulation and terminal differentiation are reviewed. Genes involved in
      Dictyostelium aggregation, slug formation, and culmination of fruiting bodies are
      discussed. 

PMID- 25872187
TI  - VEGF attenuated increase of outward delayed-rectifier potassium currents in
      hippocampal neurons induced by focal ischemia via PI3-K pathway.
AB  - We recently indicated that the vascular endothelial growth factor (VEGF) protects
      neurons against hypoxic death via enhancement of tyrosine phosphorylation of
      Kv1.2, an isoform of the delayed-rectifier potassium channels through activation
      of the phosphatidylinositol 3-kinase (PI3-K) signaling pathway. The present study
      investigated whether VEGF could attenuate ischemia-induced increase of the
      potassium currents in the hippocampal pyramidal neurons of rats after ischemic
      injury. Adult male Sprague-Dawley rats were subjected to transient middle
      cerebral artery occlusion (MCAO) to induce brain ischemia. The whole-cell patch
      clamp technique was used to record the potassium currents of hippocampal neurons
      in brain slices from the ischemically injured brains of the rats 24h after MCAO.
      We detected that transient MCAO caused a significant increase of voltage-gated
      potassium currents (Kv) and outward delayed-rectifier potassium currents (IK),
      but not outward transient potassium currents (IA), in the ipsilateral hippocampus
      compared with the sham. Moreover, we found that VEGF could acutely, reversibly
      and voltage-dependently inhibit the ischemia-induced IK increase. This inhibitory
      effect of VEGF could be completely abolished by wortmannin, an inhibitor of PI3
      K. Our data indicate that VEGF attenuates the ischemia-induced increase of IK via
      activation of the PI3-K signaling pathway. 

PMID- 25872188
TI  - ["The old doctor" devoted his life to children].

PMID- 25872189
TI  - [7 Articles on patient safety].

PMID- 25872190
TI  - [Worrying reading about the "production" of health care. "General restraint" is
      not enough].

PMID- 25872191
TI  - [Clobetasol primarily used for phimosis in children].

PMID- 25872192
TI  - [Antibiotics on loan. Even Alexander Fleming warned against drug resistance].

PMID- 25872193
TI  - [Right and wrong about the medical experts of the judicial system].

PMID- 25872194
TI  - [Not Available].

PMID- 25872195
TI  - [Not Available].

PMID- 25872196
TI  - [The intestinal microbiota affects health and disease. Dietary intake and genetic
      factors control the composition of the bacterial flora].

PMID- 25872197
TI  - [Not Available].

PMID- 25872198
TI  - [Too many blanks in the internship lottery].

PMID- 25872199
TI  - [Time for moderation and reflection regarding the AHT model].

PMID- 25872200
TI  - [Sweden needs a national strategy for nutrition and physical activity].

PMID- 25872201
TI  - [Welcome debate on costly drugs].

PMID- 25872202
TI  - [Swedish Surgical Society: "Start a dialogue with the profession about highly
      specialized care"].

PMID- 25872207
TI  - Compressed sensing for ultrasound computed tomography.
AB  - Ultrasound computed tomography (UCT) allows the reconstruction of quantitative
      tissue characteristics, such as speed of sound, mass density, and attenuation.
      Lowering its acquisition time would be beneficial; however, this is fundamentally
      limited by the physical time of flight and the number of transmission events. In
      this letter, we propose a compressed sensing solution for UCT. The adopted
      measurement scheme is based on compressed acquisitions, with concurrent
      randomised transmissions in a circular array configuration. Reconstruction of the
      image is then obtained by combining the born iterative method and total variation
      minimization, thereby exploiting variation sparsity in the image domain.
      Evaluation using simulated UCT scattering measurements shows that the proposed
      transmission scheme performs better than uniform undersampling, and is able to
      reduce acquisition time by almost one order of magnitude, while maintaining high
      spatial resolution. 

PMID- 25872206
TI  - Local Gradients in Electrotonic Loading Modulate the Local Effective Refractory
      Period: Implications for Arrhythmogenesis in the Infarct Border Zone.
AB  - Ectopic electrical activity that originates in the peri-infarct region can give
      rise to potentially lethal re-entrant arrhythmias. The spatial variation in
      electrotonic loading that results from structural remodelling in the infarct
      border zone may increase the probability that focal activity will trigger
      electrical capture, but this has not previously been investigated systematically.
      This study uses in-silico experiments to examine the structural modulation of
      effective refractory period on ectopic beat capture. Informed by 3-D
      reconstructions of myocyte organization in the infarct border zone, a region of
      rapid tissue expansion is abstracted to an idealized representation. A novel
      metric is introduced that defines the local electrotonic loading as a function of
      passive tissue properties and boundary conditions. The effective refractory
      period correlates closely with local electrotonic loading, while the action
      potential duration, conduction, and upstroke velocity reduce in regions of
      increasing electrotonic load. In the presence of focal ectopic stimuli, spatial
      variation in effective refractory period can cause unidirectional conduction
      block providing a substrate for reentrant arrhythmias. Consequently, based on the
      observed results, a possible novel mechanism for arrhythmogenesis in the infarct
      border zone is proposed. 

PMID- 25872208
TI  - Multiview matrix completion for multilabel image classification.
AB  - There is growing interest in multilabel image classification due to its critical
      role in web-based image analytics-based applications, such as large-scale image
      retrieval and browsing. Matrix completion (MC) has recently been introduced as a
      method for transductive (semisupervised) multilabel classification, and has
      several distinct advantages, including robustness to missing data and background
      noise in both feature and label space. However, it is limited by only considering
      data represented by a single-view feature, which cannot precisely characterize
      images containing several semantic concepts. To utilize multiple features taken
      from different views, we have to concatenate the different features as a long
      vector. However, this concatenation is prone to over-fitting and often leads to
      very high time complexity in MC-based image classification. Therefore, we propose
      to weightedly combine the MC outputs of different views, and present the
      multiview MC (MVMC) framework for transductive multilabel image classification.
      To learn the view combination weights effectively, we apply a cross-validation
      strategy on the labeled set. In particular, MVMC splits the labeled set into two
      parts, and predicts the labels of one part using the known labels of the other
      part. The predicted labels are then used to learn the view combination
      coefficients. In the learning process, we adopt the average precision (AP) loss,
      which is particular suitable for multilabel image classification, since the
      ranking-based criteria are critical for evaluating a multilabel classification
      system. A least squares loss formulation is also presented for the sake of
      efficiency, and the robustness of the algorithm based on the AP loss compared
      with the other losses is investigated. Experimental evaluation on two real-world
      data sets (PASCAL VOC' 07 and MIR Flickr) demonstrate the effectiveness of MVMC
      for transductive (semisupervised) multilabel image classification, and show that
      MVMC can exploit complementary properties of different features and output
      consistent labels for improved multilabel image classification. 

PMID- 25872209
TI  - Online space-variant background modeling with sparse coding.
AB  - In this paper, we propose a sparse coding approach to background modeling. The
      obtained model is based on dictionaries which we learn and keep up to date as new
      data are provided by a video camera. We observe that, without dynamic events,
      video frames may be seen as noisy data belonging to the background. Over time,
      such background is subject to local and global changes due to variable
      illumination conditions, camera jitter, stable scene changes, and intermittent
      motion of background objects. To capture the locality of some changes, we propose
      a space-variant analysis where we learn a dictionary of atoms for each image
      patch, the size of which depends on the background variability. At run time, each
      patch is represented by a linear combination of the atoms learnt online. A change
      is detected when the atoms are not sufficient to provide an appropriate
      representation, and stable changes over time trigger an update of the current
      dictionary. Even if the overall procedure is carried out at a coarse level, a
      pixel-wise segmentation can be obtained by comparing the atoms with the patch
      corresponding to the dynamic event. Experiments on benchmarks indicate that the
      proposed method achieves very good performances on a variety of scenarios. An
      assessment on long video streams confirms our method incorporates periodical
      changes, as the ones caused by variations in natural illumination. The model,
      fully data driven, is suitable as a main component of a change detection system. 

PMID- 25872210
TI  - Neutral face classification using personalized appearance models for fast and
      robust emotion detection.
AB  - Facial expression recognition is one of the open problems in computer vision.
      Robust neutral face recognition in real time is a major challenge for various
      supervised learning-based facial expression recognition methods. This is due to
      the fact that supervised methods cannot accommodate all appearance variability
      across the faces with respect to race, pose, lighting, facial biases, and so on,
      in the limited amount of training data. Moreover, processing each and every frame
      to classify emotions is not required, as user stays neutral for majority of the
      time in usual applications like video chat or photo album/web browsing. Detecting
      neutral state at an early stage, thereby bypassing those frames from emotion
      classification would save the computational power. In this paper, we propose a
      light-weight neutral versus emotion classification engine, which acts as a pre
      processer to the traditional supervised emotion classification approaches. It
      dynamically learns neutral appearance at key emotion (KE) points using a
      statistical texture model, constructed by a set of reference neutral frames for
      each user. The proposed method is made robust to various types of user head
      motions by accounting for affine distortions based on a statistical texture
      model. Robustness to dynamic shift of KE points is achieved by evaluating the
      similarities on a subset of neighborhood patches around each KE point using the
      prior information regarding the directionality of specific facial action units
      acting on the respective KE point. The proposed method, as a result, improves
      emotion recognition (ER) accuracy and simultaneously reduces computational
      complexity of the ER system, as validated on multiple databases. 

PMID- 25872211
TI  - Robust face alignment under occlusion via regional predictive power estimation.
AB  - Face alignment has been well studied in recent years, however, when a face
      alignment model is applied on facial images with heavy partial occlusion, the
      performance deteriorates significantly. In this paper, instead of training an
      occlusion-aware model with visibility annotation, we address this issue via a
      model adaptation scheme that uses the result of a local regression forest (RF)
      voting method. In the proposed scheme, the consistency of the votes of the local
      RF in each of several oversegmented regions is used to determine the reliability
      of predicting the location of the facial landmarks. The latter is what we call
      regional predictive power (RPP). Subsequently, we adapt a holistic voting method
      (cascaded pose regression based on random ferns) by putting weights on the votes
      of each fern according to the RPP of the regions used in the fern tests. The
      proposed method shows superior performance over existing face alignment models in
      the most challenging data sets (COFW and 300-W). Moreover, it can also estimate
      with high accuracy (72.4% overlap ratio) which image areas belong to the face or
      nonface objects, on the heavily occluded images of the COFW data set, without
      explicit occlusion modeling. 

PMID- 25872212
TI  - Classification on the monogenic scale space: application to target recognition in
      SAR image.
AB  - This paper introduces a novel classification strategy based on the monogenic
      scale space for target recognition in Synthetic Aperture Radar (SAR) image. The
      proposed method exploits monogenic signal theory, a multidimensional
      generalization of the analytic signal, to capture the characteristics of SAR
      image, e.g., broad spectral information and simultaneous spatial localization.
      The components derived from the monogenic signal at different scales are then
      applied into a recently developed framework, sparse representation-based
      classification (SRC). Moreover, to deal with the data set, whose target classes
      are not linearly separable, the classification via kernel combination is
      proposed, where the multiple components of the monogenic signal are jointly
      considered into a unifying framework for target recognition. The novelty of this
      paper comes from: the development of monogenic feature via uniformly
      downsampling, normalization, and concatenation of the components at various
      scales; the development of score-level fusion for SRCs; and the development of
      composite kernel learning for classification. In particular, the comparative
      experimental studies under nonliteral operating conditions, e.g., structural
      modifications, random noise corruption, and variations in depression angle, are
      performed. The comparative experimental studies of various algorithms, including
      the linear support vector machine and the kernel version, the SRC and the
      variants, kernel SRC, kernel linear representation, and sparse representation of
      monogenic signal, are performed too. The feasibility of the proposed method has
      been successfully verified using Moving and Stationary Target Acquiration and
      Recognition database. The experimental results demonstrate that significant
      improvement for recognition accuracy can be achieved by the proposed method in
      comparison with the baseline algorithms. 

PMID- 25872213
TI  - Distinguishing local and global edits for their simultaneous propagation in a
      uniform framework.
AB  - In propagating edits for image editing, some edits are intended to affect limited
      local regions, while others act globally over the entire image. However, the
      ambiguity problem in propagating edits is not adequately addressed in existing
      methods. Thus, tedious user input requirements remain since the user must densely
      or repeatedly input control samples to suppress ambiguity. In this paper, we
      address this challenge to propagate edits suitably by marking edits for local or
      global propagation and determining their reasonable propagation scopes
      automatically. Thus, our approach avoids propagation conflicts, effectively
      resolving the ambiguity problem. With the reduction of ambiguity, our method
      allows fewer and less-precise control samples than existing methods. Furthermore,
      we provide a uniform framework to propagate local and global edits
      simultaneously, helping the user to quickly obtain the intended results with
      reduced labor. With our unified framework, the potentially ambiguous interaction
      between local and global edits (evident in existing methods that propagate these
      two edit types in series) is resolved. We experimentally demonstrate the
      effectiveness of our method compared with existing methods. 

PMID- 25872214
TI  - Neighborhood Discriminant Hashing for  Large-Scale Image Retrieval.
AB  - With the proliferation of large-scale community-contributed images, hashing-based
      approximate nearest neighbor search in huge databases has aroused considerable
      interest from the fields of computer vision and multimedia in recent years
      because of its computational and memory efficiency. In this paper, we propose a
      novel hashing method named neighborhood discriminant hashing (NDH) (for short) to
      implement approximate similarity search. Different from the previous work, we
      propose to learn a discriminant hashing function by exploiting local
      discriminative information, i.e., the labels of a sample can be inherited from
      the neighbor samples it selects. The hashing function is expected to be
      orthogonal to avoid redundancy in the learned hashing bits as much as possible,
      while an information theoretic regularization is jointly exploited using maximum
      entropy principle. As a consequence, the learned hashing function is compact and
      nonredundant among bits, while each bit is highly informative. Extensive
      experiments are carried out on four publicly available data sets and the
      comparison results demonstrate the outperforming performance of the proposed NDH
      method over state-of-the-art hashing techniques.

PMID- 25872215
TI  - Burst-Modulated Waveforms Optimize Electrical Stimuli for Charge Efficiency and
      Fiber Selectivity.
AB  - We demonstrate an alternative method of designing electrical stimuli-termed burst
      modulation--for producing different patterns of nerve fiber recruitment. By
      delivering electrical charge in bursts of "pulsons"--miniature pulses-instead of
      as long continuous pulses, our method can optimize the waveform for stimulation
      efficiency and fiber selectivity. In our in vivo validation experiments, while
      maintaining C fibers of the rat vagus nerve at ~ 50% activation with different
      waveforms, the burst-modulated waveform produced 11% less A fiber activation than
      the standard rectangular pulse waveform (rectangular: 50.8+/-1.5% of maximal A
      response, mean +/- standard error of the mean; burst-modulated: 39.8 +/-1.3%),
      which equates to a 20% reduction in A fiber response magnitude. In addition, the
      burst-modulated waveform required 45% less stimulus charge per phase to maintain
      50% C fiber activation (rectangular: 20.7 +/-0.86 MUC; burst-modulated: 11.3 +/
      0.41 MUC ). Burst-modulated waveforms produced consistent patterns of fiber
      recruitment within and across animals, which indicate that our methods of
      stimulus design and response analysis provide a reliable way to study
      neurostimulation and deliver therapy.

PMID- 25872216
TI  - Unilateral Floor Stiffness Perturbations Systematically Evoke Contralateral Leg
      Muscle Responses: A New Approach to Robot-Assisted Gait Therapy.
AB  - A variety of robotic rehabilitation devices have been proposed for gait
      rehabilitation after stoke, but have only produced moderate results when compared
      to conventional physiotherapy. We suggest a novel approach to robotic
      interventions which takes advantage of mechanisms of inter-limb coordination. In
      order to test the viability of this approach, we apply unilateral floor stiffness
      perturbations via a unique robotic device and observe evoked contralateral leg
      responses in kinematics, as well as muscle activations, in healthy subjects. The
      real-time control of floor stiffness is utilized to uniquely differentiate force
      and kinematic feedback, creating novel sensory perturbations. We present results
      of repeatable and scalable evoked kinematic and muscular response of the
      unperturbed leg in healthy subjects. Moreover, we provide insight into the
      fundamental sensorimotor mechanisms of inter-leg coordination. We also lay the
      foundation for model-based rehabilitation strategies for impaired walkers by
      presenting a mathematical model that accurately describes the relationship
      between the magnitude of the stiffness perturbation and the evoked muscle
      activity. One of the most significant advantages of this approach over current
      practices is the safety of the patient, since this does not require any direct
      manipulation of the impaired leg. The novel methods and results presented in this
      paper set the foundation for a paradigm shift in robotic interventions for gait
      rehabilitation. 

PMID- 25872217
TI  - An Efficient Algorithm for Discovering Motifs in Large DNA Data Sets.
AB  - The planted (l,d) motif discovery has been successfully used to locate
      transcription factor binding sites in dozens of promoter sequences over the past
      decade. However, there has not been enough work done in identifying (l,d) motifs
      in the next-generation sequencing (ChIP-seq) data sets, which contain thousands
      of input sequences and thereby bring new challenge to make a good identification
      in reasonable time. To cater this need, we propose a new planted (l,d) motif
      discovery algorithm named MCES, which identifies motifs by mining and combining
      emerging substrings. Specially, to handle larger data sets, we design a MapReduce
      based strategy to mine emerging substrings distributedly. Experimental results on
      the simulated data show that i) MCES is able to identify (l,d) motifs efficiently
      and effectively in thousands to millions of input sequences, and runs faster than
      the state-of-the-art (l,d) motif discovery algorithms, such as F-motif and
      TraverStringsR; ii) MCES is able to identify motifs without known lengths, and
      has a better identification accuracy than the competing algorithm CisFinder.
      Also, the validity of MCES is tested on real data sets. MCES is freely available
      at http://sites.google.com/site/feqond/mces.

PMID- 25872218
TI  - Global Exponential Stability for Complex-Valued Recurrent Neural Networks With
      Asynchronous Time Delays.
AB  - In this paper, we investigate the global exponential stability for complex-valued
      recurrent neural networks with asynchronous time delays by decomposing complex
      valued networks to real and imaginary parts and construct an equivalent real
      valued system. The network model is described by a continuous-time equation.
      There are two main differences of this paper with previous works: 1) time delays
      can be asynchronous, i.e., delays between different nodes are different, which
      make our model more general and 2) we prove the exponential convergence directly,
      while the existence and uniqueness of the equilibrium point is just a direct
      consequence of the exponential convergence. Using three generalized norms, we
      present some sufficient conditions for the uniqueness and global exponential
      stability of the equilibrium point for delayed complex-valued neural networks.
      These conditions in our results are less restrictive because of our consideration
      of the excitatory and inhibitory effects between neurons; so previous works of
      other researchers can be extended. Finally, some numerical simulations are given
      to demonstrate the correctness of our obtained results. 

PMID- 25872219
TI  - Quantification of Nighttime Micturition With an Ambulatory Sensor-Based System.
AB  - Among elderly males, benign prostate syndrome (BPS) is the most common urinary
      disorder. Nocturia is one of the major symptoms of BPS and has a considerable
      influence on the quality of life. For assessment of BPS (including nocturia), the
      International Prostate Symptom Score is widely used, but questionnaires are prone
      to bias. To date, there is no objective measurement system available for
      nocturia. In this study, we present an unobtrusive and nonstigmatizing device for
      objective measurement of nighttime micturition. In a preliminary study of six
      males diagnosed with BPS and nighttime micturition >= 2*, we showed that the
      device is accurate, with an average misdetection rate of 0.32 events and a mean
      absolute deviation of 3.8% when comparing the average number of nighttime
      micturition occurrences. In this extended study, an additional nine males were
      recorded and data from an occupancy sensor were also included. The results of the
      preliminary study were confirmed with an average misdetection rate of 0.33 events
      and a mean absolute deviation of 9.1%. The system can, therefore, be used to
      objectively measure nighttime micturition and, thereby, provide the basis for
      treatment, e.g., medication efficacy assessment.

PMID- 25872220
TI  - Learning Receptive Fields and Quality Lookups for Blind Quality Assessment of
      Stereoscopic Images.
AB  - Blind quality assessment of 3D images encounters more new challenges than its 2D
      counterparts. In this paper, we propose a blind quality assessment for
      stereoscopic images by learning the characteristics of receptive fields (RFs)
      from perspective of dictionary learning, and constructing quality lookups to
      replace human opinion scores without performance loss. The important feature of
      the proposed method is that we do not need a large set of samples of distorted
      stereoscopic images and the corresponding human opinion scores to learn a
      regression model. To be more specific, in the training phase, we learn local RFs
      (LRFs) and global RFs (GRFs) from the reference and distorted stereoscopic
      images, respectively, and construct their corresponding local quality lookups
      (LQLs) and global quality lookups (GQLs). In the testing phase, blind quality
      pooling can be easily achieved by searching optimal GRF and LRF indexes from the
      learnt LQLs and GQLs, and the quality score is obtained by combining the LRF and
      GRF indexes together. Experimental results on three publicly 3D image quality
      assessment databases demonstrate that in comparison with the existing methods,
      the devised algorithm achieves high consistent alignment with subjective
      assessment. 

PMID- 25872221
TI  - Reinforcement-Learning-Based Robust Controller Design for Continuous-Time
      Uncertain Nonlinear Systems Subject to Input Constraints.
AB  - The design of stabilizing controller for uncertain nonlinear systems with control
      constraints is a challenging problem. The constrained-input coupled with the
      inability to identify accurately the uncertainties motivates the design of
      stabilizing controller based on reinforcement-learning (RL) methods. In this
      paper, a novel RL-based robust adaptive control algorithm is developed for a
      class of continuous-time uncertain nonlinear systems subject to input
      constraints. The robust control problem is converted to the constrained optimal
      control problem with appropriately selecting value functions for the nominal
      system. Distinct from typical action-critic dual networks employed in RL, only
      one critic neural network (NN) is constructed to derive the approximate optimal
      control. Meanwhile, unlike initial stabilizing control often indispensable in RL,
      there is no special requirement imposed on the initial control. By utilizing
      Lyapunov's direct method, the closed-loop optimal control system and the
      estimated weights of the critic NN are proved to be uniformly ultimately bounded.
      In addition, the derived approximate optimal control is verified to guarantee the
      uncertain nonlinear system to be stable in the sense of uniform ultimate
      boundedness. Two simulation examples are provided to illustrate the effectiveness
      and applicability of the present approach. 

PMID- 25872222
TI  - Coupled Dictionary Learning for the Detail-Enhanced Synthesis of 3-D Facial
      Expressions.
AB  - The desire to reconstruct 3-D face models with expressions from 2-D face images
      fosters increasing interest in addressing the problem of face modeling. This task
      is important and challenging in the field of computer animation. Facial contours
      and wrinkles are essential to generate a face with a certain expression; however,
      these details are generally ignored or are not seriously considered in previous
      studies on face model reconstruction. Thus, we employ coupled radius basis
      function networks to derive an intermediate 3-D face model from a single 2-D face
      image. To optimize the 3-D face model further through landmarks, a coupled
      dictionary that is related to 3-D face models and their corresponding 3-D
      landmarks is learned from the given training set through local coordinate coding.
      Another coupled dictionary is then constructed to bridge the 2-D and 3-D
      landmarks for the transfer of vertices on the face model. As a result, the final
      3-D face can be generated with the appropriate expression. In the testing phase,
      the 2-D input faces are converted into 3-D models that display different
      expressions. Experimental results indicate that the proposed approach to facial
      expression synthesis can obtain model details more effectively than previous
      methods can. 

PMID- 25872223
TI  - Ambient Coarse Particulate Matter and Hospital Admissions in the Medicare Cohort
      Air Pollution Study, 1999-2010.
AB  - BACKGROUND: In recent years a number of studies have examined the short-term
      association between coarse particulate matter (PM(10-2.5)) and mortality and
      morbidity outcomes. These studies, however, have produced inconsistent
      conclusions. OBJECTIVES: We estimated both the national- and regional-level
      associations between PM(10-2.5) and emergency hospitalizations for both
      cardiovascular and respiratory disease among Medicare enrollees >= 65 years of
      age during the 12-year period 1999 through 2010. METHODS: Using air pollution
      data obtained from the U.S. Environmental Protection Agency air quality
      monitoring network and daily emergency hospitalizations for 110 large urban U.S.
      counties assembled from the Medicare Cohort Air Pollution Study (MCAPS), we
      estimated the association between short-term exposure to PM(10-2.5) and
      hospitalizations using a two-stage Bayesian hierarchical model and Poisson log
      linear regression models. RESULTS: A 10-MUg/m3 increase in PM(10-2.5) was
      associated with a significant increase in same-day cardiovascular
      hospitalizations [0.69%; 95% posterior interval (PI): 0.45, 0.92]. After
      adjusting for PM2.5, this association remained significant (0.63%; 95% PI: 0.38,
      0.88). A 10-MUg/m3 increase in PM(10-2.5) was not associated with a significant
      increase in respiratory-related hospitalizations. CONCLUSIONS: We found
      statistically significant evidence that daily variation in PM(10-2.5) is
      associated with emergency hospitalizations for cardiovascular diseases among
      Medicare enrollees >= 65 years of age. This association was robust to adjustment
      for concentrations of PM2.5. CITATION: Powell H, Krall JR, Wang Y, Bell ML, Peng
      RD. 2015. Ambient coarse particulate matter and hospital admissions in the
      Medicare Cohort Air Pollution Study, 1999-2010. Environ Health Perspect 123:1152
      1158; http://dx.doi.org/10.1289/ehp.1408720.

PMID- 25872227
TI  - Understanding the Accuracy of Parental Perceptions of Child Physical Activity: A
      Mixed Methods Analysis.
AB  - BACKGROUND: Interventions to increase children's physical activity (PA) have
      achieved limited success. This may be attributed to inaccurate parental
      perceptions of their children's PA and a lack of recognition of a need to change
      activity levels. METHODS: Fifty-three parents participated in semistructured
      interviews to determine perceptions of child PA. Perceptions were compared with
      children's measured MVPA (classified as meeting or not meeting UK guidelines) to
      produce 3 categories: "accurate," "over-estimate," and "under-estimate."
      Deductive content analysis was performed to understand the accuracy of parental
      perceptions. RESULTS: All parents of children meeting the PA guidelines
      accurately perceived their child's PA; while the majority of parents whose child
      did not meet the guidelines overestimated their PA. Most parents were unconcerned
      about their child's PA level, viewing them as naturally active and willing to be
      active. Qualitative explanations for perceptions of insufficient activity
      included children having health problems and preferences for inactive pursuits,
      and parents having difficulty facilitating PA in poor weather and not always
      observing their child's PA level. Social comparisons also influenced parental
      perceptions. CONCLUSIONS: Strategies to improve parental awareness of child PA
      are needed. Perceptions of child PA may be informed by child "busyness," being
      unaware of activity levels, and social comparisons.

PMID- 25872230
TI  - The editor's offering.

PMID- 25872228
TI  - Alternating Sitting and Standing Increases the Workplace Energy Expenditure of
      Overweight Adults.
AB  - BACKGROUND: To determine whether alternating bouts of sitting and standing at
      work influences daily workplace energy expenditure (EE). METHODS: Twenty-three
      overweight/obese office workers (mean +/- SD; age: 48.2 +/- 7.9 y, body mass
      index: 29.6 +/- 4.0 kg/m2) undertook two 5-day experimental conditions in an
      equal, randomized order. Participants wore a "metabolic armband" (SenseWear
      Armband Mini) to estimate daily workplace EE (KJ/8 h) while working (1) in a
      seated work posture (SIT condition) or (2) alternating between a standing and
      seated work posture every 30 minutes using a sit-stand workstation (STAND-SIT
      condition). To assess the validity of the metabolic armband, a criterion measure
      of acute EE (KJ/min; indirect calorimetry) was performed on day 4 of each
      condition. RESULTS: Standing to work acutely increased EE by 0.7 [95% CI 0.3-1.0]
      KJ/min (13%), relative to sitting (P = .002). Compared with indirect calorimetry,
      the metabolic armband provided a valid estimate of EE while standing to work
      (mean bias: 0.1 [-0.3 to 0.4] KJ/min) but modestly overestimated EE while sitting
      (P = .005). Daily workplace EE was greatest during the STAND-SIT condition (mean
      condition difference [95% CI]: 76 [8-144] KJ/8-h workday, P = .03). CONCLUSIONS:
      Intermittent standing at work can modestly increase daily workplace EE compared
      with seated work in overweight/obese office workers.

PMID- 25872232
TI  - British sub-aqua club (BSAX) diving incidents report 2013.

PMID- 25872233
TI  - Thomas Richard Hennessy 1940-2014.

PMID- 25872234
TI  - Hydrophobicity: the link between bubbles, bubblers and autoimmunity?

PMID- 25872237
TI  - Reply from the author.

PMID- 25872238
TI  - New study highlights need to scale up violence prevention efforts globally.

PMID- 25872239
TI  - Health partners unite to build stronger systems for health in Ebola-affected
      countries.

PMID- 25872240
TI  - Jan Mikulicz-Radecki (1850-1905): his impact on modern medicine.
AB  - Abstract Jan Mikulicz-Radecki (1850-1905) was the cofounder of modern surgery,
      aseptic techniques,and the inventor of gastroscopy, but his professional
      accomplishments go far beyond the field of surgical treatment. Various medical
      achievements are named in his honor, including the name of the cells that he
      discovered in rhinoscleroma, the name of Mikulicz disease, and the name of an
      ointment that he developed and continues to be used in the treatment of wounds
      and ulcers in surgery and dermatology. Noteworthy are also his interdisciplinary
      approach towards diagnosis and treatment, and his cordial attitude towards his
      patients.

PMID- 25872242
TI  - In memoriam: George Dever Selfridge, 1924-2014.

PMID- 25872243
TI  - Xylooligosaccharides: an economical prebiotic from agroresidues and their health
      benefits.
AB  - Oligosaccharides and dietary fibres are non-digestible food ingredients that
      preferentially stimulate the growth of prebiotic Bifidobacterium and other lactic
      acid bacteria in the gastro-intestinal tract. Xylooligosaccharides (XOS) provide
      a plethora of health benefits and can be incorporated into several functional
      foods. In the recent times, there has been an over emphasis on the microbial
      conversion of agroresidues into various value added products. Xylan, the major
      hemicellulosic component of lignocellulosic materials (LCMs), represents an
      important structural component of plant biomass in agricultural residues and
      could be a potent bioresource for XOS. On an industrial scale, XOS can be
      produced by chemical, enzymatic or chemo-enzymatic hydrolysis of LCMs. Chemical
      methods generate XOS with a broad degree of polymerization (DP), while enzymatic
      processes will be beneficial for the manufacture of food grade and
      pharmaceutically important XOS. Xylooligomers exert several health benefits, and
      therefore, have been considered to provide relief from several ailments. This
      review provides a brief on production, purification and structural
      characterization of XOS and their health benefits.

PMID- 25872244
TI  - Synergic actions of polyphenols and cyanogens of peanut seed coat (Arachis
      hypogaea) on cytological, biochemical and functional changes in thyroid.
AB  - In animals, long-term feeding with peanut (Arachis hypogaea) seed coats causes
      hypertrophy and hyperplasia of the thyroid gland. However, to date there have
      been no detailed studies. Here, we explored the thyroidal effects of dietary
      peanut seed coats (PSC) in rats. The PSC has high levels of pro-goitrogenic
      substances including phenolic and other cyanogenic constituents. The PSC was
      mixed with a standard diet and fed to rats for 30 and 60 days, respectively.
      Animals fed with the PSC-supplemented diet showed a significant increase in
      urinary excretion of thiocyanate and iodine, thyroid enlargement, and hypertrophy
      and/or hyperplasia of thyroid follicles. In addition, there was inhibition of
      thyroid peroxidase (TPO) activity, 5'-deiodinase-I (DIO1) activity, and (Na+-K+)
      ATPase activity in the experimental groups of rats as compared to controls.
      Furthermore, the PSC fed animals exhibited decreased serum circulating total T4
      and T3 levels, severe in the group treated for longer duration. These data
      indicate that PSC could be a novel disruptor of thyroid function, due to
      synergistic actions of phenolic as well as cyanogenic constituents.

PMID- 25872245
TI  - Addition of citral controls ROS and reduces toxicity in 5-fluorouracil treated
      Schizosaccharomyces pombe cells.
AB  - In systemic therapy, chemotherapeutic drugs, often, cause considerable side
      effects; and combination of natural compounds lessen the extent of such effects.
      In the present study, combined effect of citral and 5-fluorouracil was studied in
      Schizosaccharomyces pombe cells. The antagonistic combination index found was at
      0.01 and 0.025 mM of citral with 40 MUg or higher concentration of 5
      fluorouracil. The combined treatment was so effective that higher number of cells
      underwent apoptosis compared to individual treatment of 5-fluorouracil. Citral
      controlled ROS levels and increased survival of normal cells. Several
      differentially expressed proteins observed in the citral treatment could further
      help understanding its mechanism of action.

PMID- 25872246
TI  - Evaluation of immunostimulatory activity of Chyawanprash using in vitro assays.
AB  - Chyawanprash is an ayurvedic formulation used in Indian traditional medicinal
      system for its beneficial effect on human health. We investigated the
      immunostimulatory effects of Chyawanprash (CHY) using in vitro assays evaluating
      the secretion of cytokines such as Tumor Necrosis Factor-alpha (TNF-alpha),
      Interleukin-1beta (IL-1beta) and Macrophage Inflammatory Protein-1-alpha (MIP-1
      alpha) from murine bone marrow derived Dendritic Cells (DC) which play pivotal
      role in immunostimulation. The effects of CHY on phagocytosis in murine
      macrophages (RAW264.7) and Natural Killer (NK) cell activity were also
      investigated. At non-cytotoxic concentrations (20-500 MUg/ml), CHY enhanced the
      secretion of all the three cytokines from DC. CHY also stimulated both,
      macrophage (RAW264.7) as well as NK cell activity, in vitro. In conclusion, the
      data substantiates the immunoprotective role of CHY at cellular level mediated by
      immunostimulation in key immune cells viz. dendritic Cells, macrophages and NK
      cells.

PMID- 25872247
TI  - Genetic characterization and authentication of Gardenia jasminoides in different
      regions of China by using improved RAPD analysis.
AB  - Gardenia jasminoides is a common garden medicinal plant known for its anticancer,
      anti-inflammatory, anti-thrombic, anti-fibrotic, antiviral, hepatoprotective,
      lung-protective, renal-protective, retina-protective and neuroprotective
      activities. It is found in several regions of the world, including China, but
      information about its genetic characteristics is limited. Here, we employed an
      improved method of random amplified polymorphic DNA (RAPD) analysis (with
      increased RAMP time) to investigate the genetic link between G. jasminoides
      samples collected from six different regions of Southern China. Total 26 RAPD
      primers were selected randomly, among which 23 primers generated reproducible
      polymorphic amplification bands. A total of 174 bands were obtained, where each
      primer had amplified 5-13 bands with an average of 7.56 bands per primer. The
      band size ranged approximately 150-2200 bp. Cluster dendrogram was obtained based
      on the improved RAPD amplification profiles, which showed that the similarity
      coefficients among six varieties of G. jasminoides ranged 0.67-0.88. To our
      knowledge, this is the first report of genetic characterization of G. jasminoides
      using improved RAPD analysis, which may be useful for the preservation of genetic
      diversity and identification of Gardenia population.

PMID- 25872248
TI  - Lipophilic metabolite profiling of maize and sorghum seeds and seedlings, and
      their pest spotted stem borer larvae: a standardized GC-MS based approach.
AB  - In order to better understand the biochemical interactions and to identify new
      biomarkers for plant resistance against insects, we proposed a suitable
      lipophilic profiling method for insects and their host plants. The critical
      components of GC-MS based analysis are: sample amount, extraction,
      derivatization, temperature gradient, run time, and identification of peaks. For
      lipophilic metabolite profiling of maize and sorghum, and their insect pest,
      spotted stem borer larvae, we recommend 100 mg sample weight for seeds and insect
      samples (whole insect body), and 200 mg for seedlings. Maize and sorghum seeds
      required less time for fat extraction in comparison to their seedlings and the
      pest fed on these seedlings. GC-MS was standardized for better separation and
      intensity of peaks using different temperature gradients in the range of 180-300
      C. A total of 48 lipophilic compounds encompassing various classes based on their
      functional groups such as fatty acids, fatty alcohols, hydrocarbons, sterols and
      terpenoids, vitamin derivative, etc. were separated in the seedlings (30), seeds
      (14), and the pest (26) in the retention time range of 3.22 to 29.41 min. This
      method could be useful to study nutritional aspects of different field crops in
      relation to various stresses apart from the analysis of lipophilic compounds for
      better understanding of insect-plant interactions.

PMID- 25872250
TI  - In vitro propagation of the Garden Heliotrope, Valeriana officinalis L.:
      influence of pre-chilling and light on seed germination.
AB  - Valeriana officinalis is an important medicinal herb commonly found in Kashmir
      valley. This study forms an important preliminary step for in-vitro micro
      propagation of V. officinalis from breaking the seed dormancy, inducing rapid
      seed germination and its subsequent micro propagation. We investigated the
      influence of pretreatment of V. officinalis seeds with reduced temperature and
      light on seed germination and in-vitro propagation. Culture of explants from
      cultivated seeds have demonstrated its potential for in vitro propagation and
      plantlet regeneration. Individual as well as combinations of treatments such as
      temperature and light availability influenced the germination of seeds variedly.
      Unchilled seeds of V. officinalis were given dip in GA3 (200 ppm) for 24, 48 and
      120 h. Seeds treated with GA3 for 24 h and kept in darkness showed the best
      results, i.e. 48%. Seeds pretreated with GA3 for 120 h and incubated in dark
      showed 40% germination. Pre-chilling up to 72 h and kept in light showed maximum
      germination of 60% followed by 40% kept in darkness. Pre-chilling for 48 h
      resulted in 40 and 25% seed germination in light and darkness, respectively. GA3
      pre-treatment for 72 h and 24 h pre chilling were most effective in inducing seed
      germination. Maximum shoot response was obtained on MS enriched with BAP (1 mg/L)
      + IAA (0.1 mg/L) combinations using shoot tips as explants. Multiple shoot
      regeneration from shoot apices was recorded on BAP (1 mg/L) and BAP (1 mg/L) +
      IAA (0.1 mg/L).

PMID- 25872249
TI  - Effect of carbon and nitrogen sources on in vitro flower and fruit formation and
      withanolides production in Withania somnifera (L.) Dunal.
AB  - We studied the influence of sucrose and nitrogen concentration on in vitro
      flowering and fruit setting in elongated shoots of Withania somnifera. BA (1.5
      mg/l) and IAA (0.3 mg/l) on MS medium supplemented with 4% sucrose showed 67% of
      in vitro flower induction frequency, 9 flowers/shoot, 4 fruits/shoot and 11
      seeds/fruit in elongated-shoots. Different concentrations of nitrogen sources (L
      glutamine, adenine sulphate, ammonium nitrate, potassium nitrate and sodium
      nitrate 5-25 mg/l) were tested in combination with 4% sucrose and BA at 1.5 mg/l
      and IAA at 0.3 mg/l. Highest number of flowers (20 flowers/shoot; 2.2-fold) and
      fruits (16 fruits/shoot; 3.39-fold), fruit setting (12 seeds/fruit; 1.08-fold) at
      a higher frequency (88%) were achieved on MS medium augmented with 15 mg/l
      adenine sulphate with same PGRs and sucrose concentration. The maximum production
      of withanolide A (0.68 mg/g DW) and withanolide B (0.77 mg/g DW) was recorded in
      in vitro fruits. Highest accumulation of withaferin A (2 mg/g DW) was quantified
      from in vitro flowers, whereas, it was low in in vitro fruits (0.49 mg/g DW
      withaferin A). However, withanone (0.23 mg/g DW) was found accumulated uniformly
      in both in vitro flowers and fruits compared to control.

PMID- 25872251
TI  - Suspected nosocomial infections with multi-drug resistant E. coli, including
      extended-spectrum beta-lactamase (ESBL)-producing strains, in an equine clinic.
AB  - Enterobacteriaceae such as Escherichia coli are common commensals as well as
      opportunistic and obligate pathogens. They cause a broad spectrum of infectious
      diseases in various hosts, including hospital-associated infections. In recent
      years, the rise of extended spectrum beta-lactamase (ESBL)-producing E. coli in
      companion animals (dogs, cats and horses) has been striking. However, reports on
      nosocomial infections are mostly anecdotic. Here we report on the suspected
      nosocomial spread of both ESBL-producing and non-ESBL-producing multi-drug
      resistant E. coli isolates in three equine patients within an equine clinic.
      Unlike easy-to-clean hospitalization opportunities available for small animal
      settings like boxes and cages made of ceramic floor tiles or stainless steel,
      clinical settings for horses are challenging environments for infection control
      programs due to unavoidable extraneous material including at least hay and
      materials used for horse bedding. The development of practice-orientated
      recommendations is needed to improve the possibilities for infection control to
      prevent nosocomial infections with multi-drug resistant and other transmissible
      pathogens in equine clinical settings.

PMID- 25872252
TI  - [Increase in antimicrobial resistance of Salmonella from food to fluoroquinolones
      and cephalosporins--a review of data from ten years].
AB  - Animal derived food is a relevant source of human infections with Salmonella
      enterica. In this paper we analyse the presence of Salmonella in meat with
      respect to the observed serovars and their resistance to the fluoroquinolone
      ciprofloxacin and 3rd generation cephalosporins in the years 2003 to 2012. Data
      originated from 8176 isolates that were isolated from meat, characterized in the
      National Reference Laboratory for Salmonella and tested for antimicrobial
      resistance in the National Reference Laboratory for antimicrobial resistance in
      this time period. The analysis reveals substantial differences in resistance
      patterns between isolates from different types of meat and different serovars.
      Frequent serovars were mostly associated with one type of meat, suggesting an
      additional influence of specific characteristics of the serovars besides the
      effect of selection pressure excerted by antimicrobial treatments. Results show a
      clear increase in resistance to fluoroquinolones and 3rd generation
      cephalosporins that was most prominent in isolates from poultry meat. Although
      the number of human infections with Salmonella in Germany decreased sharply in
      recent years, results indicate a substantial exposure of consumers to Salmonella
      that are resistant to important antimicrobials via meat.

PMID- 25872253
TI  - Multidrug resistant Acinetobacter baumannii in veterinary medicine--emergence of
      an underestimated pathogen?
AB  - The proportion of multidrug resistant bacteria causing infections in animals has
      continuously been increasing. While the relevance of ESBL (extended spectrum beta
      lactamase)-producing Enterobacteriaceae spp. and MRSA (methicillin resistant
      Staphylococcus aureus) is unquestionable, knowledge about multidrug resistant
      Acinetobacter baumannii in veterinary medicine is scarce. This is a worrisome
      situation, as A. baumannii are isolated from veterinary clinical specimens with
      rising frequency. The remarkable ability of A. baumannii to develop multidrug
      resistance and the high risk of transmission are known in human medicine for
      years. Despite this, data regarding A. baumannii isolates of animal origin are
      missing. Due to the changing role of companion animals with closer contact
      between animal and owner, veterinary intensive care medicine is steadily
      developing. It can be assumed that the number of "high risk" patients with an
      enhanced risk for hospital acquired infections will be rising simultaneously.
      Thus, development and spread of multidrug resistant pathogens is envisioned to
      rise. It is possible, that A. baumannii will evolve into a veterinary nosocomial
      pathogen similar to ESBL-producing Enterobacteriaceae and MRSA. The lack of
      attention paid to A. baumannii in veterinary medicine is even more worrying, as
      first reports indicate a transmission between humans and animals. Essential
      questions regarding the role of livestock, especially as a potential source of
      multidrug resistant isolates, remain unanswered. This review summarizes the
      current knowledge on A. baumannii in veterinary medicine for the first time. It
      underlines the utmost significance of further investigations of A. baumannii
      animal isolates, particularly concerning epidemiology and resistance mechanisms.

PMID- 25872254
TI  - [Epidemiology and clinical features of Acinetobacter baumannii infections in
      humans].
AB  - Over the past 30 years, Acinetobacter (A.) baumannii has been increasingly
      recognized as an important human pathogen. In contrast to the "non-baumannii"
      Acinetobacter spp. which rarely cause diseases in humans, the members of the A.
      baumannii-group (A. baumannii, A. pittii and A. nosocomialis) are important
      nosocomial pathogens. A. baumannii itself has been implicated as a causative
      agent in various severe infections such as bloodstream infections, pneumonia, or
      meningitis, mainly in immunocompromised patients in the intensive care unit
      setting. The combination of intrinsic and increasing acquired resistance to
      various antimicrobial agents often limits the therapeutic options. Currently,
      none of the available antimicrobial agents with potential activity against
      Acinetobacter spp. such as, carbapenems, tigecycline, and colistin can be
      considered uniformly active against all A. baumannii strains. In addition, the
      incidence of multi- or panresistant A. baumannii-strains is increasing worldwide.
      Due to the unique combination of high resistance to adverse environmental
      conditions, the propensity for clonal spread and the extensive resistance to
      antimicrobial agents, A. baumannii is one of the most important bacterial
      pathogens of our time.

PMID- 25872255
TI  - Resistance plasmids in ESBL-encoding Escherichia coli isolates from humans, dogs
      and cats.
AB  - We characterized ESBL-producing Escherichia coli isolates from diseased dog, cat
      and human sources for their plasmid content. Plasmids with different Inc groups
      and combinations of resistance genes were detected in these isolates. The pan
      genome of the plasmid-associated genes was found to be large, indicating
      diversity of the gene pool among the plasmids. No commonly occurring plasmids
      with similar gene content in isolates from dog, cats and humans were detected.

PMID- 25872256
TI  - [Estimation of the transfer of ESBL-producing Escherichia coli to humans in
      Germany].
AB  - In 2011 EFSA has evaluated the risk for the consumer caused by ESBL-/AmpC
      producing bacteria in food of animal origin and in livestock animals. Human-to
      human transfer in hospitals.and in the community was considered as the most
      relevant route of transmission for ESBL-producing E. coli. ESBL-/AmpC-producing
      E. coli are in Germany, as in many other Member States of the European Union,
      widely spread in food of animal origin and in livestock animals. In an assessment
      of the relevance of livestock animals as reservoir for ESBL-/AmpC-producing E.
      coli as well as for ESBL-coding resistance genes the heterogeneity of the
      resistance genes, plasmids and bacteria in animals, foods and humans needs to be
      considered. In this context, both, the clonal spread of bacteria as well as
      horizontal transfer of resistance genes, e. g. by plasmids, have to be analyzed.
      Whereas studies in The Netherlands identified poultry as the most relevant
      reservoir, the transfer of ESBL-gene carrying plasmids from pigs to the farmers
      was demonstrated in Denmark. First attempts to quantify the relevance of
      livestock animals as reservoir for ESBL-producing E. coli in Germany showed, that
      the proportions of the most frequent ESBL-resistance genes are quite different
      between animal and human derived E. coli isolates. If in addition properties of
      the bacterial cells, e.g. resistance to several antibiotic classes are
      considered, only a small proportion of human isolates showed the same patterns as
      animal isolates. The results achieved so far demonstrate that certain ESBL-types
      are prevalent in all livestock populations investigated. Currently, the majority
      of cases of colonizations with ESBL-producing E. coli among humans cannot be
      directly linked to livestock and food-producing animals as reservoirs. This
      reflects that transmission routes are more complex and other reservoirs and
      sources including human-human interactions have to be taken into consideration.

PMID- 25872257
TI  - Effects of carry-over of fluoroquinolones on the susceptibility of commensal
      Escherichia coli in the intestinal microbiota of poultry.
AB  - Due to the frequent use of antibacterials in veterinary medicine as well as in
      human medicine the occurrence of antibacterial resistance rises worldwide. But
      independent of the usage of antimicrobials the microbiota from animals as well as
      from humans already harbour a diversity of resistance genes. As a consequence of
      manufacturing animal production the treatment of livestock in case of illness is
      carried out via feed or drinking water. This automatically implies several risks.
      It has been demonstrated that an antibiotic treatment of livestock via feed or
      drinking water cause an accumulation of antibiotics and their metabolites in the
      direct environment of animals. This can lead to a carry-over or rather a
      resumption of the antimicrobials and their metabolites. Thus, the aim of this
      study was to determine the influence of carry-over of enrofloxacin as a
      representative of the fluoroquinolones on the development of bacterial resistance
      of commensal E. coli in the intestinal microbiota of poultry. Therefore four
      different treatment groups were provided and the minimal inhibitory
      concentrations (MICs) of commensal E. coli were measured: One group acted as
      untreated control, another one was therapeutically treated with the recommended
      dosage. The third and fourth group were exposed to different "carry-over dosages"
      for three weeks, 3% of the recommended dosage were applied to the third and 10%
      to the fourth group. To determine the influence of a therapeutic treatment on a
      prestressed microbiota, both groups were treated with the recommended dosage for
      five days. The present study demonstrates that every kind of exposure of the
      commensal microbiota of poultry with enrofloxacin leads to an amplification and
      selection of resistant E. coli, which persist in the commensal microbiota. A long
      term exposure of gut microbiota, which already harbour non-wild type E. coli,
      with high levels of carry-over of fluoroquinolones may lead to a development of
      high-level clinically resistant E. coli in the commensal microbiota. It has to be
      investigated to which extent antimicrobial leftovers occur in animal production.

PMID- 25872258
TI  - [Infection control and hygiene management in equine hospitals].
AB  - With the rising importance of nosocomial infections in equine hospitals,
      increased efforts with regard to biosecurity and infection control are necessary.
      This even more since nosocomial infections are often associated with multi-drug
      resistant pathogens. Consequently, the implementation of targeted prevention
      programs is essential. Since nosocomial infections are usually multifactorial
      events, realization of only a single measure is rarely effective to overcome
      nosocomial spread in clinical practice. Equine patients may be colonized at
      admission with multi-drug resistant pathogens such as methicillin resistant
      Staphylococcus aureus (MRSA) and/or extended spectrum beta lactamase-producing
      (ESBL-) Enterobacteriaceae. Regardless of their individual resistance properties,
      these bacteria are common and usually unnoticed colonizers of either the
      nasopharynx or the intestinal tract. Also viral diseases caused by equine
      herpesvirus 1 (EHV-1) and EHV-4 may reach a clinic by patients which are latently
      infected or in the incubation period. To prevent nosocomal outbreaks, achieve an
      interruption in the infection chain and to eradicate infectious agents from the
      hospital environment, a professional hospital management is necessary. This
      should be adapted to both the wide range of pathogens causing nosocomial
      infections and the individual needs of equine patients. Amongst others, this
      approach includes a risk classification of equine patients at admission and
      information/enlightenment of the animal owners at discharge. An efficient
      management of inpatients, a targeted hygiene management and clear
      responsibilities with respect to biosecurity together with a surveillance of
      nosocomial infections form the cornerstone of infection control in equine
      hospitals.

PMID- 25872259
TI  - [The search for novel antibiotics--strategies and current approaches].
AB  - The emergence and increasing prevalence of resistant pathogens primarily in
      intensive care units demand the discovery and development of new antimicrobial
      agents and new therapeutic approaches. This review provides an overview of new
      antibacterial agents that are currently in research and development pipelines.
      Data were collected from published literature, meeting abstracts, public
      government and company websites. Well-known antibacterial classes like beta
      lactams, quinolones, macrolides, tetracyclines, and pleuromutilins are
      represented by new molecules with enhanced antibacterial or pharmacological
      properties. Furthermore, compounds acting on targets not previously exploited are
      in various stages of research and development. Targeting bacterial virulence is
      an alternative approach to antibacterial therapy. Neutralizing bacterial toxins
      by using antibodies is an established anti-virulence strategy which encourages
      increased research into other virulence targets. Certain virulence factors have
      already been shown to be meaningful targets for small molecules.

PMID- 25872260
TI  - [The becoming of fatty cells, biological function of trophology, biological
      reactions of exo- and endotrophy in phylogenesis. The functional difference
      between visceral fatty cells and subcutaneous adipocytes].
AB  - The becoming of visceral fatty, cells in phylogenesis occurred many billions
      years before subcutaneous adipocytes. The pool of visceral fatty cells realizes
      biologic functions of trophology and homeostasis, endoecology, and adaptation
      from the early stages of phylogenesis. The subcutaneous adipocytes realize
      phylogenetically late biologic function of locomotion. The visceral fatty cells
      have no receptors to insulin and all subcutaneous adipocytes are insulin
      dependent. In biologic function of trophology, both visceral fatty cells and
      subcutaneous adipocytes realize biologic reaction of exotrophy, biologic reaction
      of depositing and biologic reaction of endotrophy. It is supposed that the most
      common cause of obesity is disorder of biologic reaction of depositing of fatty
      acids in form of triglycerides. It is considered as a basis of that dysfunction
      of visceral fatty cells (metabolic syndrome) and insulin-dependent adipocytes
      (obesity) takes so often a character of metabolic pandemic. The fatty cells
      absorb fatty acids in form of non-polar triglycerides, deposit them in lipid
      drops and free fatty acids into intercelluar medium in form of polar unesterified
      fatty acids. The visceral fatty cells had been formed in paracrin cenosis of
      enterocytes and in it microsome protein transferring triglycerides formed early
      type of chylomicrons. The visceral fatty cells and adipocytles are
      phylogenetically, regulatory, functionally and pathophysiologically different
      cells. Therefore, they are to be considered separately. Not only visceral fatty
      cells and adipocytes but all cells of areolar tissue at level of cenosis of cells
      secrete many humoral mediators of paracrin regulation. The other modes of
      regulation are unknown. Leptin is a specific mediator of visceral fatty cells and
      adiponectin is a mediator of subcutaneous adipocytes.

PMID- 25872261
TI  - [The fetal proteins in prognosis of development of pneumonia in patients with
      ischemic stroke].
AB  - The searching of laboratory predictors of pneumonia in patients with ischemic
      stroke is an actual issue. The fetal proteins can be such biomarkers. The study
      was carried out to determine significance of such fetal proteins as alpha
      fetoprotein, cancerous embryonic antigen, CA 19-9, CA 125, CA 15-3, CA 72-4,
      CYFRA 21-1 for prognosis of development of pneumonia in patients with ischemic
      stroke. The study included sampling of 216 patients in acute period of ischemic
      stroke. All patients were measured level of fetal proteins in first day from
      onset of disease using electrochemiluminescence immunoassay. It is demonstrated
      that CA 72-4 has the most significance for prognosis of development of pneumonia
      from all analyzed proteins and complications of ischemic stroke. The probability
      ratio relatively to other fetal proteins added up to 0.460 (CL 95% 0.267-0.791,
      p=0.011), to other complications--0.629 (CL 95% 0.433-0.913, p=0.015). The
      threshold value of CA 72-4 for development of pneumonia added up to 0.82 (CL 95%
      0.68-0.96, p=0.011) U/ml. Under lower level of CA 72-4 the risk of development of
      pneumonia increases. Under higher level of CA 72-4 there is statistical
      probability of absence of developmnent of pneumonia. The threshold value was
      lower than reference interval which in the study added up to 0.85-1.42 U/ml. The
      detection of level of CA 72-4 on first day after onset of stroke in patients can
      be recommended for establishing of group of high risk of development of pneumonia
      and implementation of therapeutic activities.

PMID- 25872262
TI  - [The laboratory evaluation of pathogenic factors under retarded consolidation of
      fractures of bones of lower extremities].
AB  - The study was carried out to comparatively analyze metabolic profile and content
      of growth factors in blood serum of patients with retarded consolidation of
      fractures of bones of lower extremities. The evaluation was applied to
      concentration of metabolites, growth factors and enzyme activity of blood serum
      in 13 patients with retarded consolidation of fractures of thigh and shank bones
      (main group). The comparative group included 14 patients with solid fractures of
      thigh and shank bones. The analysis established that as compared to patients with
      solid fractures of bones, in patients with retarded consolidation of fractures
      blood serum contained reliably higher concentration of triglycerides, products of
      glycolysis, epidermal growth factor and transforming growth factors TGF-alpha and
      TGF-beta2. The content of vitamin E and insullin-like growth factor (IGF-1) was
      decreased The given markers can be labeled as potential markers of diagnostic and
      prognosis of development of retarded consolidation of fractures.

PMID- 25872263
TI  - [The concentration of procalcitonin in blood andi enteric exudation in patients
      at early post-operation period].
AB  - The study sampling included 46 patients operated on the occasion of acute
      surgical pathology of abdominal organs. The concentration of procalcitonin was
      analyzed at 2-3 days after operation in simultaneously obtained samples of blood
      serum and exudation of small intestine. The level of procalcitonin was analyzed
      using enzyme-linked immunosorbent assay with test-systems with sensitivity 0.01
      ng/ml. The concentration of procalcitonin in content of small intestine was lower
      than in blood serum (p<0.001) and in most samples of enteric exudation (n=33) did
      not exceed 0.01 ng/ml. The analysis of correlation interdependences established
      that concentration of procalcitonin in intestinal exudation has no dependencies
      with its level in blood serum. The admixture of blood as a result of
      traumatization of mucous membrane under application of naso-jejunal probe is one
      of main causes of occurrence of procalcitonin in content of intestine.

PMID- 25872264
TI  - [The new diagnostic algorithms in early period of acute intoxications with
      psychotropic preparations].
AB  - The patients with acute intoxications with psychotropic preparations were
      analyzed for physical chemical characteristics of blood albumin at admission to
      hospital. The common level of reduced thiols in albumin fraction was analyzed
      too. The more frequent cases of unfavorable course of disease were noted at
      indicator rate less than 250 mkmol/l than at rates higher than 250 mkmol/l. This
      occurrence permits to consider this indicator as prognostically significant and
      to evaluate individual risk of unfavorable course of disease in the given
      category of patients. Under acute intoxications with psychotropic preparations
      appllying of fluorescent albumin test permits already at fist day of
      hospitalization to reveal a subgroup of patients with higher risk of subsequent
      development of pneumonia.

PMID- 25872265
TI  - [The evaluation of oxidative stress in women with sleep disturbances in post
      menopause conditions using integrated indicator].
AB  - The article presents results of individual evaluation of coefficient of oxidative
      stress as an integral indicator of balance of the system "lipids peroxidation
      antioxidant defense" in women with sleep disturbances in post menopause
      conditions. The condition of the system "lipids peroxidation-antioxidant defense"
      was evaluated using analysis of content of substrates of oxidation of processes
      of lipid peroxidation with conjugated double bonds, diene conjugates, ketodienes
      and conjugated trienes, TBC-active products of retinol alpha-tokoferol, reduced
      and oxidized glutathione, activity of superoxiddismutase in blood. The
      application of coefficient of oxidative stress permitted to demonstrate
      differences in processes of lipids peroxidation in women with the same diagnosis
      and use it as a justification of individual approach under prescription of
      antioxidant therapy.

PMID- 25872266
TI  - [The low content of apolipoprotein E as a risk factor of increasing of ratio
      apolipoprotein B/A-1 in healthy males with normal lipemia].
AB  - The relationship of ratio of apolipoprotein (apo) B/apoA-1 with other indicators
      of lipid metabolism in healthy people with normal lipemia was analyzed. The
      dependence of ratio of apolipoprotein (apo) B/apoA-1 from content of apoE
      (X2=8.20; p=0.042) was established. Under low indicators of apoE risk of
      detection of unfavorable ratio apolipoprotein (apo) B/apoA-1 (higher than 0.9)
      increases (probability ratio 0.61, CI 95% 0.41-0.88, p=0.009). It is possible
      that low content of apoE results in deceleration of elimination and accumulation
      of lipoproteins in blood. This occurrence is followed by alteration of balance
      between apoE and apoA-1. In general, among patients with unfavorable ratio
      apoB/apoA-1 in spite of normal lipemia were detected higher indicators of
      triglycerides and atherogenic index of plasma and lower values of ratio of
      cholesterol lipoproteins of low density and apoB. This observation indicates on
      increasing of quantity triglyceride-reach lipoproteins and little solid
      lipoproteins of low density. Therefore, low content of apoE in blood can be
      considered as a predictor of increasing of ratio apoB/apoA-1 in healthy persons.

PMID- 25872267
TI  - [The cytomorphologic characteristics of parathyroids under hyperparathyroidism].
AB  - The article presents the results of intravital studying of cytomorphologic
      characteristics of elements of tissue of parathyroids obtained under thin-needle
      aspiration biopsy in patients with hyperparathyroidism. The analysis was applied
      to 84 fragments of cell material from node formations in projection of anatomic
      localization of parathyroids and in projection of lobes and isthmus of thyroid
      gland. The cytologic preparations colored with Pappenheim azure-eosin staining
      were analyzed using light microscopy. The results were compared with data of
      histological study of post-operation material. The following cytomorphologic
      signs of tissue of parathyroids under hyperparathyroidism: heterogeneity of
      population of cells of glandular epithelium--presence of main (dark, light) and
      oxyphilous parathyrocytes with prevalence of main parathyrocytes; occurrence of
      expressed intracellular contacts in groupings of parathyrocytes with formation of
      rosette-strand like structures or compact assemblies as well as occurrence of
      dark polymorphic granules positioned in cytoplasm of epithelium cells and
      intercellular medium.

PMID- 25872268
TI  - [The support of immune safety of hemotransfusions under implementation of
      cardiosurgery operations].
AB  - The index and structure of allosensibilization of patients according transfusion
      dangerous antigens of erythrocytes were identified. The purpose of action was to
      evaluate risk of development of post-transfusion hemolytic complications under
      application of hemotransfusions during operative interventions on heart and
      vessels. The immune anti-erythrocytes antibodies were detected in 81 cases (1.7%)
      and their main percentage formed antibodies of Rhesus system (67.7%). The
      antibodies to antigens of other systems like anti-K (10%), anti-S (2.5%), anti
      Jka (1.2%), anti-Fya (1.2%), anti-Lea (3.7%) were more rarely detected. The
      estimated index of sensitization in patients made up to 1.7% that testifies
      higher degree of alloimmunization of examined patients and potential risk of
      development of post-transfusion complications of hemolytic type under
      hemotrasfusions. The received data was used as a background to develop and to
      implement algorithm of immune hematologic examination of patients of
      cardiosurgery profile. This approach permits minimizing risk of alloimmunization
      of recipients, to forecast and to prevent development of complications under
      transfusion of erythrocyte-containing components of donor blood that
      significantly enhances quality of transfusion therapy.

PMID- 25872269
TI  - [The molecular genetic characteristic of RNA of human enterovirus detected in bio
      test from child with serous meningitis].
AB  - The article considers molecular genetic characteristic of RNA of human
      enterovirus detected in bio-test from child with serous meningitis. The
      nucleotide sequence of genome DNA is analyzed. In 98% it is identical to
      corresponding nucleotide sequences of strains of human enterovirus A serotype 71
      detected in China.

PMID- 25872270
TI  - [Yhe pre-analytic stage in studies of surveillance of HIV strains resistant to
      anti-retrovirus preparations in the Privolzhskiy Federal Okrug].
AB  - The article presents analysis of activities concerning organization of pre
      analytic stage of monitoring of HIV resistance to anti- retrovirus preparations
      on territories of the Privolzhskiy Federal Okrug. The medical records of patients
      receiving anti-retrovirus therapy and appointment cards to detect drug resistance
      of HIV from territorial centers of prevention and control of AIDS and infectious
      diseases are analyzed. The results of testing of specialists of service of
      prevention of AIDS/HIV with questionnaire "Characteristics of pre-analytical
      stage under implementation of molecular genetic and immunologic analyses"
      developed in the Privolzhskiy okrug center of prevention and control ofAIDS and
      samples of bio-tests obtained during coming-outs in regions of okrug were
      included into analysis too. The failures in implementation of pre-analytical
      stage were established. Hence, the subsequent decreasing of informativeness of
      analyses or inexpediency or even impossibility of application of testing of AIDS
      drug resistance. The recommendations are proposed concerning main directions of
      work to enhance pre-analytical stage of analysis of AIDS resistance to anti
      retrovirus preparations.

PMID- 25872271
TI  - [The differentiation of specimiens of Vibrio parahaemolyticua and Vobrio
      alginolyticus].
AB  - Vibrio parahaemolyticua and Vobrio alginolyticus are phylogenetically closely
      related species. They have common ecological niches, same cultural features and
      similar biochemical characteristics. The phenotype variability and taxonomy
      similarity of strains of these species impedes differentiation of Vibrio
      parahaemolyticua and Vobrio alginolyticus according biochemical characteristics.
      To obtain reliable results of diagnostic application of additional methods of
      differentiation and identification these two species of bacteria are needed. The
      study was organized to comparatively evaluate effectiveness of biochemical
      testing, polymerase chain reaction analysis and mass-spectrometry technique in
      differentiation of species of Vibrio parahaemolyticua and Vibrio alginolyticus.
      The study implemented analysis of methods of differentiation of species of Vibrio
      parahaemolyticua and Vibrio alginolyticus using model of collection including
      atypical strains of these species. To substantiate species belonging of strains
      of Vibrio parahaemolyticua and Vobrio alginolyticus such techniques are to be
      additionally applied to biochemical methods of identification as polymerase chain
      reaction analysis with species-specific primers of genes of metalloproteinase
      (collagenase) vppC and vapC. The MALDI-TOFF method of mass-spectrometry can be
      used as additional effective method of identification and inter-species
      differentiation of species of Vibrio parahaemolyticua and Vibrio alginolyticus
      isolated from various sources.

PMID- 25872272
TI  - [The comparative evalution of informativeness of immunologic and molecular
      genetic methods and means during stages of specific indication of melioidosis
      agent].
AB  - The reference-center of monitoring of agents of glanders and melioidosis carried
      out testing of reagents kits for diagnostic of agent of melioidosis and other
      close-related species of Burkholderiae in vitro. At the stage of specific
      identification of pathogenic Burkholderiae the diagnostic possibilities of
      commercial and experimental kits of reagents for express- and rapid analysis were
      evaluated. The criteria of evaluation of diagnostic value of kits of reagents
      were sensitivity, specificity and time of implementation of studies. The analysis
      with application of mono- and multi-locus amplification systems, including real
      time polymerase chain reaction permitted during 5-6 hours to implement
      identification and differentiation of Burkholderia pseufomallei, B. thailandensis
      and B. cepacia.

PMID- 25872273
TI  - [The mode of differential diagnostic of and acute alcoholic gastroenteritis].
AB  - The study was carried out to develop mode of differential diagnostic of
      salmonella and acute alcoholic gastroenteritis on the basis of phospholipid
      specter of blood serum. The indicators of phospholipid fractions of blood serum
      were analyzed in 50 healthy persons, 50 patients with acute alcoholic
      gastroenteritis and 50 patients with salmonella gastroenteritis were analyzed.
      The relative content of following fractions of whole phospholipids were analyzed-
      total lysophospholipids, sphyngomiyelin, phosphatidcholine,
      phosphatidyletanolamin. The phospholipid spectrum of blood serum can be applied
      in differential diagnostic of salmonella gastroenteritis and acute alcoholic
      gastroenteritis. The disorders of metabolism of lipids under given pathological
      conditions have a multidirectional character. The salmonella gastroenteritis is
      characterized by decreasing of relative content of total lysophospholipids and
      increasing of phosphatidcholine as compared with standard conditions. The acute
      alcoholic gastroenteritis is characterized by increasing of relative content of
      total lysophospholipids and phosphatidcholine and decreasing of level of
      phosphatidcholine. The content of total Iysophospholipids in blood serum is lower
      on 35% or 30.0 mg% permits diagnosing acute alcoholic gastroenteritis. The
      content of phosphaltidcholine in blood serum higher than 40% or 50 mg% permits
      diagnosing salmonella gastroenteritis.

PMID- 25872274
TI  - [Influence of physico-chemical properties of materials on the postcompressional
      parameters of tablets].
AB  - The number of tablets marketed with a score line to aid divisibility is
      increasing. The subdivision of scored tablets in order to ensure dose flexibility
      may be an easier and cheaper solution from the aspect of production. However, to
      ensure the appropriate mechanical properties and divisibility of tablets so as to
      guarantee consequent dosing is a difficult problem, which is influenced by many
      properties of the applied materials, such as the physicochemical behaviour, the
      plasticity, the degree of elasticity, the mechanism of compression, etc. These
      exert a significant influence on the postcompressional properties of tablets, and
      hence on the subdivision of tablets. Despite the considerable difficulties, the
      increasing importance in paediatrics and the ever stricter requirements of the
      drug authorities, the subdivision of scored tablets is a poorly studied field.
      This paper deals with the influence of physico-chemical properties of materials
      on the postcompressional parameters of tablets, and especially on the subdivision
      of tablets. For measurement of the force required to break tablets into halves, a
      laboratory-constructed hardness tester was utilized.

PMID- 25872275
TI  - [Particle size reduction using acoustic cavitation].
AB  - Different pharmaceutical technological processes have been used for modification
      of the physico-chemical and biopharmaceutical properties of drugs. Changes of
      crystal size, distribution and morphology can open up new, alternative
      administration routes, e.g. intranasally and the pulmonary route, where the
      particle size is a determining factor. A wet grinding method based on acoustic
      cavitation (the collapse of bubbles or voids formed by sound waves) is a novel
      possibility for modification of the properties of particles. During our work this
      wet grinding technique was studied. The effect of this method was investigated on
      particle size reduction. The samples were treated with extreme sonication
      parameters. The effect of the concentration of the polymer was examined on the
      particle size reduction. Meloxicam was chosen as a model crystalline drug because
      of its poor aqueous solubility. The structural characterization and the
      morphological analysis of the dried products were carried out by DSC, XRPD and
      SEM. It was found that the acoustic cavitation resulted in crystalline micronized
      product.

PMID- 25872276
TI  - [Application of biosensors from the point of drug research].
AB  - With the increasing number of protein active agents produced by the
      biotechnological route, the suitable analytical methods will also be important.
      The detection of small changes of protein and the monitoring of the processes of
      the biotechnological procedure are important. Biosensors can be applied for the
      detection of very low concentrations with nearly 100% selectivity. The aims of
      our work are to give basic information about biosensors, about their grouping and
      potential field of application.

PMID- 25872277
TI  - [Recent results in research on oscillatory chemical reactions].
AB  - The mechanisms of the complicated periodical phenomenas in the nature (e.g.
      hearth beat, sleep cycle, circadian rhythms, etc) could be understood with using
      the laws of nonlinear chemical systems. In this article the newest result in the
      research of the subfield of nonlinear chemical dynamics aimed at constructing
      oscillatory chemical reactions, which are novel either in composition or in
      configuration, are presented. In the introductory part the concept of chemical
      periodicity is defined, then the forms as it can appear in time and space and the
      methods of their study are discussed. Detailed description of the experimental
      work that has resulted in two significant discoveries is provided. A method was
      developed to design pH-oscillators which are capable of operating under close
      conditions. The batch pH-oscillators are more convenient to use in some proposed
      applications than the equivalent CSTR variant. A redox oscillator that is new in
      composition was found. The permanganate oxidation of some amino acids was shown
      to take place according to oscillatory kinetics in a narrow range of the
      experimental parameters. The KMnO4 - glycine - Na2HPO4 system represents the
      first example in the family of manganese based oscillators where amino acids is
      involved. In the conclusion formal analogies between the simple chemical and some
      more complicated biological oscillatory phenomena are mentioned and the
      possibility of modeling periodic processes with the use of information gained
      from the studies of chemical oscillations is pointed out.

PMID- 25872279
TI  - Addressing patient complaints and perceptions through communication.

PMID- 25872280
TI  - Single-payer health care and Vermont: lessons.

PMID- 25872281
TI  - Presence of gingivitis and periodontitis significantly increases hospital charges
      in patients undergoing heart valve surgery.
AB  - OBJECTIVE: To examine the prevalence and impact of gingivitis and periodontitis
      in patients having heart valve surgical procedures. METHODS: Nationwide Inpatient
      Sample for the years 2004-2010 was used. All patients who had heart valve
      surgical procedures were selected. Prevalence of gingivitis/periodontitis was
      examined in these patients. Impact of gingivitis/periodontitis on hospital
      charges, length of stay, and infectious complications was examined. RESULTS:
      596,190 patients had heart valve surgical procedures. Gingivitis/periodontitis
      was present in 0.2 percent. Outcomes included: median hospital charges ($175,418
      with gingivitis/ periodontitis versus $149,353 without gingivitis/periodontitis)
      and median length of stay (14 days with gingivitis/periodontitis versus 8 days
      without gingivitis/periodontitis). After adjusting for the effects of patient-
      and hospital-level confounding factors, hospital charges and length of stay were
      significantly higher (p < 0.001) in those with gingivitis/periodontitis compared
      to their counterparts. Further, patients with gingivitis/periodontitis had
      significantly higher odds for having bacterial infections (OR = 3.41, 95% CI =
      2.33-4.98, p < 0.0001) when compared to those without gingivitis/periodontitis.
      CONCLUSION: Presence of gingivitis and periodontitis is associated with higher
      risk for bacterial infections and significant hospital resource utilization.

PMID- 25872282
TI  - Karen Rafeld: leader extraordinaire.

PMID- 25872283
TI  - What every dentist should know about subcutaneous emphysema.

PMID- 25872284
TI  - Self-mutilation during orthodontic treatment.

PMID- 25872285
TI  - Lack of dental insurance is correlated with edentulism.
AB  - PURPOSE: The correlation between insurance status and edentulism has not
      previously been reported in a population with known access to a dentist, and
      little is known about patient demographics in corporate dental settings. This
      study investigated patient demographics of a former dental franchise in Chicopee,
      Massachusetts, and examined a correlation between dental insurance and edentulism
      in this group. The correlation of edentulism with age, gender, and dental risk
      factors (diabetes, temporomandibular disorder, trouble with previous dental work,
      or oral sores and ulcers) was also examined. MATERIALS AND METHODS: This was a
      retrospective case study. Age, gender, and presence of dental risk factors were
      recorded from the patient medical history intake form. Dentate status was
      recorded from patient odontograms. Dental insurance status was obtained from
      billing records. Data was aggregated and deidentified. Descriptive and bivariate
      statistics and logistic regression models were used to identify associations (p
      value <= 0.05 significance). RESULTS: Of 1,123 records meeting inclusion
      criteria, 52.54 percent of patients had dental insurance, 26.27 percent had at
      least one dental risk factor, and 18.17 percent were edentulous. Age and
      insurance status were significantly correlated with edentulism. Correcting for
      age, individuals without insurance were 1.56 times as likely to be edentulous.
      CONCLUSION: This case study provides insight into patient demographics that might
      seek care in a corporate setting and suggests that access to a dentist alone may
      not be adequate in preserving the adult dentition; dental insurance may also be
      important to health. As the corporate dental practice model continues to grow,
      these topics deserve further study.

PMID- 25872286
TI  - A clinico-pathologic correlation: squamous cell carcinoma.

PMID- 25872287
TI  - Mixed-density pericoronal lesions.

PMID- 25872288
TI  - The dentist is coming! The dentist is coming!

PMID- 25872289
TI  - [Application of micro-power system in the surgery of tooth extraction].
AB  - Tooth extraction is a common operation in oral surgery. Traditional-extraction
      instruments, such as bone chisel, elevator, and bone hammer, lead to not only
      severe trauma but also unnecessary complications, and patients easily become
      nervous and apprehensive if tooth extraction is performed using these violent
      instruments. In recent years, with the develop- ment of minimally invasive
      concept and technology, various micro-power instruments have been used for tooth
      extraction. This innovative technology can reduce the iatrogenic trauma and
      complications of tooth extraction. Additionally, this technology can greatly
      decrease the patient's physical and mental pressure. The new equipment
      compensates for the deficiency of traditional tooth extraction equipment and
      facilitates the gradual replacement of the latter. Diverse micro-power systems
      have distinct strengths and weaknesses, so some auxiliary instruments are still
      needed during tooth extraction. This paper focuses on the various micro-power
      systems for tooth extraction and tries to compare the advantages and
      disadvantages of these systems. Selection and usage of auxiliary equipment are
      also introduced. Thus, this paper provides reference for the proper application
      of the micro-power systems in tooth extraction.

PMID- 25872290
TI  - [Effects of hirudin on the expression of basic fibroblast growth factor and
      transforming growth factor-beta1 in human gingival fibroblasts].
AB  - OBJECTIVE: This study aimed to investigate the effects of hirudin on the
      expression of transforming growth factor (TGF-beta1) and basic fibroblast growth
      factor (bFGF) in human gingival fibroblasts (HGFs) in vitro, as well to explore
      its func- tion in the mechanism of gingival remodeling. METHODS: After culturing
      was performed with classic tissue-explant method, HGFs were derived from normal
      gingival and gingival hyperplasia tissues followed by orthodontic treatments with
      different concentrations of hirudin. The mRNA and protein expression levels of
      TGF-beta1 and bFGF were respectively detected by real time quantity polymerase
      chain reaction and immunocytochemistry. RESULTS: Compared with normal HGFs, TGF
      beta1 expression promoted collagen synthesis of fibroblasts, whereas bFGF
      collagen synthesis was decreased in hyperplasia HGFs without hirudin (P < 0.05).
      Hirudin significantly upregulated the expression levels of bFGF but downregulated
      TGF-beta1 in hyperplasia HGFs (P < 0.05). CONCLUSION: Orthodontic force may
      influence the balance of collagen synthesis and degradation in HGFs. Hirudin may
      modulate the balance of HGF collagen metabolism, thereby promoting gingival
      remodeling.

PMID- 25872291
TI  - [Expression and clinical significance of nuclear factor kappaB/B cell lymphoma-2
      signal pathway and glycogen synthase kinase 3beta in oral squamous cell
      carcinoma].
AB  - OBJECTIVE: This study aims to examine the expression of nuclear factor kappaB (NF
      kappaB)/B cell lymphoma-2 (Bcl-2) signal pathway and glycogen synthase kinase
      3beta (GSK-3beta) in oral squamous cell carcinoma (OSCC) and provide references
      for the early diagnosis and prognosis evaluation of OSCC. METHODS: A total of 55
      cases of OSCC and 10 cases of paracan- cerous mucosa were examined in this study.
      Their expressions of GSK-3beta, NF-kappaB and Bcl-2 were detected using the SP me
      thod immunohistochemistry. The correlation between their expression in OSCC and
      the clinical and pathological peculiarity of OSCC was analyzed. RESULTS: The
      positive expression of GSK-3beta, NF-kappaB, and Bcl-2 in OSCC were significantly
      higher than that in paracancerous mucosa (P < 0.01). The expression of GSK-3beta,
      NF-kappaB, and Bcl-2 had no obvious relationship with patient's age, sex, and
      clinical stages of the disease (P > 0.05). The expression of Bcl-2 was
      significantly correlated with the degree of tumor differentiation (P < 0.05),
      whereas the expression of GSK-3beta and NF-kappaB in OSCC had no obvious relation
      ship with the degree of tumor differentiation (P > 0.05). Strong positive
      correlations were observed among the expressions of GSK-3beta, NF-kappaB, and Bcl
      2 (P < 0.05). CONCLUSION: The positive expression of GSK-3beta, NF-kappaB, and
      Bcl-2 in OSCC are sig- nificantly higher than that in paracancerous mucosa.
      Detecting GSK-3beta, NF-kappaB, and Bcl-2 in OSCC may have implications in the
      early diagnosis and prognosis evaluation of OSCC.

PMID- 25872292
TI  - [Changes in pain threshold and glial cell line-derived neurotrophic factor in rat
      model of trigeminal neuralgia].
AB  - OBJECTIVE: This research aims to study the changes in pain threshold and glial
      cell line-derived neurotrophic factor (GDNF) in a Sprague Dawley (SD) rat model
      oftrigeminal neuralgia. METHODS: A total of 36 male SD rats were randomly divided
      into three groups: operative, sham-operative, and control. In the operative
      group, a chronic constriction injury (CCI) was caused by placing loose chromic
      gut ligatures around the right infraorbital nerve (ION). In the sham-operative
      group, the right ION was subjected to the same procedure, but without ligation.
      In the control group, the right ION was not subjected to any treatment. The pain
      thresholds of the three groups were recorded at different times after the
      operation. The GDNF expression in each group was analyzed via immunohistochemical
      staining. RESULTS: An allodynia to mechanical stimulation in the region of the
      ligated ION was observed starting on the 2nd week after operation. Pain
      thresholds started to increase gradually from the 6th week and returned to the
      original level at the 10th to 12th week after operation. Cells that expressed the
      GDNF markedly increased in number in the operative group with changes observed at
      different times. CONCLUSION: We use chronic constriction injury to the
      infraorbital nerve (CCI-ION) to establish a trigeminal neuralgia-like animal
      model in SD rats. GDNF may play a role in regulating pain by promoting the
      restoration and regeneration of nerve fibers.

PMID- 25872293
TI  - [Effect of microRNA-17 on osteogenic differentiation of advanced glycation end
      products-stimulated human periodontal ligament stem cells].
AB  - OBJECTIVE: This study aims to detect microRNA-17(mir-17) expression on the
      osteogenic differentiation of advanced glycation end products (AGEs)-stimulated
      hunman periodontal ligament stem cells (HPDLSCs) and to analyze the influence of
      these cells on this process. METHODS: HPDLSCs were isolated using limited
      dilution technique. After osteogenic differentiation occurred, different time
      points of mir-17 expression in the experimental groups were detected by real time
      polymerase chain reaction (PCR). The mir-17 overexpression and inhibition were
      evaluated using cell transfection technique. Differences in gene expressions were
      detected by real time PCR; differences in protein expressions were analyzed by
      Western blot. RESULTS: The mir-17 expression was reduced after osteogenic
      differentiation occurred at 3, 7, and 14 d compared with that in the control
      group (P < 0.05). The expression levels of bone sialoprotein (BSP), Runt-related
      transcription factor-2 (Runx-2)and alkaline phosphatase (ALP) in the experimental
      groups were lower than those in the mimic control group when mir-17 expression
      increased. In addition, the protein expression levels of Runx-2 in the
      experimental groups were lower than those in the control group. The expression
      levels of BSP, Runx-2 and ALP in the experimental groups were higher than those
      in the inhibitor control group when mir-17 expression decreased. Likewise, the
      protein expression levels of Runx-2 in the experimental groups were higher than
      those in the control group. CONCLUSION: AGEs inhibit the osteogenic
      differentiation of HPDLSCs by affecting mir-17 expression.

PMID- 25872294
TI  - [Notch signaling promotes receptor activator of nuclear factor kappa B ligand
      induced ostoclastogenesis of RAW264.7 cells in vitro].
AB  - OBJECTIVE: This study aims to explore the effect of Notch signaling depression on
      the receptor activator of nuclear factor kappa B ligand (RANKL)-induced
      osteoclastogenesis of RAW264.7 cells. METHODS: Mice RAW264.7 cells were cultured
      and differentiated into osteoclasts with the induction of RANKL. The expressions
      of Notch1, Notch2, Deltal, Jagged1, Hes1, tartrate-resistant acid phosphatase
      (TRAP), and Cathepsin K genes during osteoclastogenesis were analyzed using real
      time polymerase chain reaction. Osteoclast formation was analyzed using TRAP
      assay with suppression of Notch receptors by a selective gamma-secretase
      inhibitor (GSI). RESULTS: Notch1, Notch2, Delta1, Jagged1, and Hes1 expressions
      in RAW264.7 cells were upregulated following 50 ng . mL-RANKL stimulation for 3
      d, concomitant with the expression of the osteoclast differentiation markers TRAP
      and Cathepsin K. Notch2 and Jagged1 had the most remarkable increase in the Notch
      family members. GSI inhibited RANKL-induced osteoclastogenesis of RAW264.7 cells
      and Hes1 expression dose-dependently. CONCLUSION: Notch signaling activation may
      promote RANKL-induced osteoclastogenesis of RAW264.7 cells.

PMID- 25872295
TI  - [Influence of 7-dehydrocholesterol reductase gene silencing on the fusion of
      mouse palatal shelves].
AB  - OBJECTIVE: RNA interference was applied to knockdown the Dhcr7 gene in mouse
      embryonic palatal shelves to facilitate understanding of the function of Dhcr7
      gene variants in the fusion of palatal shelves. METHODS: The pAdTrack-CMV-siDhcr7
      was constructed using the specific siRNA sequence of Dhcr7 from C57BL/6J mouse.
      The pAdTrack-CMV- siDhcr7 of positive clones was reconstructed in vitro, and the
      recombinant adenovirus pAdEasy-1-siDhcr7 of kanamycin resistance was screened.
      The adenovirus vector DNA was then prepared for transfecting the embryonic
      palatal shelves. Thirty pairs of embryonic palatal shelves at 13.5 d gestational
      age were harvested and then randomly divided into the following three groups:
      normal control group (n = 10), which included palatal shelves inculture medium
      without cholesterol; blank adenovirus control group (n = 10), which included
      palatal shelves in culture medium without cholesterol and blank adenovirus; and
      experimental group (n = 10), which included palatal shelves in culture medium
      without cholesterol and adenovirus encoding Dhcr7 siRNA. At 48 h after in vitro
      cultivation, the mRNA and protein of the palatal shelves were obtained for
      scanning electron microscopy (SEM), reverse transcription polymerase chain
      reaction (RT-PCR), and Western blot analyses. RESULTS: SEM showed that the
      palatal shelves of the normal control and blank adenovirus control groups fused
      and formed continuous palates, whereas those of the experimental group was almost
      undeveloped but exhibited large gaps between the two palatal shelves. RT-PCR and
      Western blot analyses showed that the mRNA and protein of Dhcr7 in the
      experimental group decreased compared with those in the normal control group with
      a significant difference (P < 0.05). CONCLUSION: Results indicate that Dhcr7 gene
      silencing affects the fusion of palatal shelves. Thus, Dhcr7 gene may serve a
      function in the normal development of palates.

PMID- 25872296
TI  - [Investigation of Wnt/beta-catenin signaling pathway on regulation of Runx2 in
      cementoblasts under mechanical stress in vitro].
AB  - OBJECTIVE: Periodontal tissue remodeling includes remodeling of alveolar bone,
      periodontal ligament, and cementum. Cementoblast plays a main role in repairing
      root resorption. Canonical Wnt/beta-catenin signaling can promote the odontogenic
      differentiation in osteoblast. However, the mechanism on how the orthodontic
      force influences the function of cementoblast and the relationship between the
      canonical Wnt/beta-catenin signaling and Runx2 of cementoblast are not yet known.
      The aim of this study is focus on this relationship. METHODS: OCCM30
      cementoblasts were subjected to mechanical strain by four-point bending system
      with tension stress for 0, 3, 6, and 12 h. They were pretreated with different
      concentrations of Dikkopf-1 (DKK1) for 48 h. Western blot analysis was performed
      to detect the beta-catenin levels in the nucleus. Runx2 mRNA was observed by real
      time quantitative polymerase chain reaction (RT-PCR). OCCM30 cementoblasts were
      then pretreated with 150 ng . mL(-1) DKK1 for 48 h and subjected to mechanical
      strain by FX4000T system with tension stress for 12 h. Western blot analysis was
      conducted to detect the beta-catenin levels in the nucleus, and Runx2 mRNA was
      observed by RT-PCR. RESULTS: OCCM30 cementoblasts had significantly higher Runx2
      mRNA and beta-catenin levels after being loaded with mechanical stress. The
      amount of Runx2 mRNA in OCCM30 cementoblasts was significantly decreased by DKK1.
      When OCCM30 cemento-blasts were pretreated with DKK1 without stress, their beta
      catenin level was significantly decreased by DKK1 and Wnt signaling was blocked.
      When they were not pretreated with stress, the beta-catenin level with DKK1 was
      lower than that without DKK1. Without DKK1, the beta-catenin level in OCCM30
      cemento- blasts increased afterbeing loaded with mechanical stress. With DKK1,
      the beta-catenin level in OCCM30 cementoblasts, which were loaded with mechanical
      stress, was higher than that without mechanical stress. CONCLUSION: Cementoblasts
      had higher Runx2 mRNA expression under mechanical stress because of the Wnt/beta
      catenin signaling pathway effect.

PMID- 25872297
TI  - [Contrast-enhanced CT for the diagnosis of mandibular invasion caused by oral
      cancers: a systematic review].
AB  - OBJECTIVE: To assess the diagnostic efficacy of contrast-enhanced CT in
      diagnosing mandibular invasion of oral cancers. METHODS: PubMed, Excerpta Medica
      Database (EMBASE), the European Grey Literature Database, Chinese Biomedical
      Literature Database (CBM), and CQVIP were searched electronically on January 03,
      2014. Hand-searching was also performed on 19 relevant Chinese journals. The
      methodological quality assessment, as suggested in Cochrane Handbook, and the
      data extraction of the studies included were performed by two reviewers in
      duplicate. Meta-analysis was conducted using the Meta Disc 1.4 software. RESULTS:
      Fourteen studies that involved 642 participants were included. Among the seven
      prospective studies, one had a low bias risk and the rest had unclear bias risks.
      When mandibular invasion was diagnosed the Meta-analysis results showed that the
      pooled sensitivity (SEN) was 0.718 [95% confidence interval (CI), 0.665-0.767],
      the pooled specificity (SPE) was 0.909 (95% CI, 0.872-0.938), the area under
      curve (AUC) was 0.906 1, and the Q* was 0.837 8. When mandibular medullary
      invasion was diagnosed, the SEN was 0.787 (0.643-0.893), the SPE was 0.904 (0.790
      0.968), the AUC was 0.949 6, and the Q* was 0.890 0. The Meta-regression results
      showed that the smaller slide thickness had a higher diagnosis efficacy.
      CONCLUSION: CT showed a high efficacy in diagnosing mandibular or medullary
      invasion caused by oral cancers. With a high SPE, contrast-enhanced CT can
      confirm the clinical diagnosis of bone invasion effectively. In addition,
      selecting a smaller slide thickness CT can increase diagnosis efficacy.

PMID- 25872298
TI  - [Three years follow-up observation and analysis of caries status of primary and
      permanent teeth among 652 6-year- old children in Sichuan Province].
AB  - OBJECTIVE: This longitudinal study aimed to investigate the caries status of
      primary and permanent teeth among 6-year-old children in Sichuan Province from
      2010 to 2012. METHODS: A sample that comprised 652 6-year-old children from six
      different elementary schools (three represented the urban areas, and the other
      three represented the rural areas) were examined according to a baseline, with
      follow-up examinations at 1, 2, and 3 years. Eruption and caries experience were
      re- corded using World Health Organization criteria. RESULTS: The prevalence
      rates of primary tooth caries of 6-year-old children in Sichuan Province for 3
      years were 74.23% (484/652), 75.61% (493/652), and 81.90% (534/652). The filling
      rate of the primary teeth was 5.87% (145/2,471) in 2012, with significant
      differences (P < 0.01) between the urban areas [10.84% (133/ 1,227)] and rural
      areas [0.96% (12/1,244)]. The total pit and fissure rate of the first molar was
      14.11% (92/652) in 2012, with significant differences between the two areas (P <
      0.01) [rural: 0.66% (2/303); urban: 25.79% (90/349)]. CONCLUSION: The pre-
      valence of caries in the primary and permanent teeth of 6-year-old children was
      high. An increasing prevalence tendency was observed as the age increased. The
      prevalence of first molar caries indicated that prevention and control of dental
      caries should be performed as early as possible.

PMID- 25872299
TI  - [Effect of repeated sintering on the color and translucency of dental lithium
      disilicate-based glass ceramic].
AB  - OBJECTIVE: To evaluate the effect of repeated sintering on the color and
      translucency of dental lithium disilicate-based glass ceramic. METHODS: Thirty
      disc specimens (10 mm in diameter, and 1.00 mm +/- 0.01 mm in thickness) were
      fabricated using an IPS e.max Press HT A2 ingot and then randomly divided into
      six groups (SO, S1, S2, S3, S4, and S5) (n = 5). Each group was sintered 0, 1, 2,
      3, 4, and 5 times individually according to the manufacturer's recommendation.
      After polishing, ultrasonic cleaning, and drying, the color parameters (L*, a*,
      and b* values) and transmittance (tau) of all the specimens were measured using a
      ShadeEye NCC dental colorimeter and a TM-2 spectrophotometer, respectively.
      Subsequently, C*ab and DeltaE were calculated. The results were statistically
      analyzed using SPSS 17.0 software for ANOVA and LSD. RESULTS: After repeated
      sintering, the L* value significantly decreased (P < 0.05), and the a*, b*, and
      C*ab values initially increased and then decreased (P < 0.05). The color
      parameters (L*, a*, and b*) and the C*ab values of group S3 were higher than
      those of the other groups. The tau values initially increased and then decreased
      (P < 0.05), and these values were optimal when sintered twice. In terms of
      transmittance (tau), statistical differences existed between the following
      groups: S0 and S2, S0 and S3,.S2 and S5, and S3 and S5 (P < 0.05). Compared with
      group S0, the color differences DeltaE were 0.89 minimally and 2.01 maximally
      after different sintering times, which can be clinically acceptable. CONCLUSION:
      Repeated sintering can affect the color and translucency of the IPS e.max Press
      lithium disilicate-based glass ceramic, but the color difference can be
      clinically acceptable.

PMID- 25872300
TI  - [Using Coben analysis to evaluate the therapeutic effect of maxillary protraction
      on maxillary maldevelopment].
AB  - OBJECTIVE: We aims to evaluate the therapeutic effect of maxillary protraction on
      maxillary maldevelopment using Coben analysis to illustrate the advantages of
      Coben analysis in identifying pathogenic mechanisms and in designing treatment
      plans for Class III malocclusions. METHODS: A total of 120 patients were
      diagnosed to have skeletal Class I maloc- clusions with maxillary maldevelopment.
      These patients were selected as the subjects of the present research. Maxillary
      protraction was exerted to promote maxilla growth. Cephalometric analysis was
      conducted by using Coben analysis and angle analyses of Beijing Medical
      University to collect data before and after maxillary protraction. RESULTS:
      According to Coben analysis measurements, the height of facies cranii increased
      after maxillary protraction. The depth of lower face decreased, whereas that of
      mid-face increased and the Ptm-A value increased significantly in the mid-face (P
      < 0.001). In the angle ana- lysis of Beijing Medical University, SNA, ANB, U1/NA,
      U1/SN, MP/SN, and Y-axis angles increased significantly (P < 0.001), whereas SNB,
      U1/L1 (P < 0.001), and L1/MP (P < 0.05) decreased. CONCLUSION: Maxillary
      protraction has a significant effect on growing skeletal Class III malocclusions
      withthe chief mechanism of Ptm-A value just diagnosed as minor by Coben analysis.
      Coben analysis is visual and clear in identifying pathogenic mechanisms of Class
      III malocclusions.

PMID- 25872301
TI  - [Comparison of treatment outcomes in patients with maxillary dentoalveolar
      protrusion by applying different anchorage methods: a three-dimensional model
      study].
AB  - OBJECTIVE: This study aims to compare the treatment outcomes in patients with
      maxillary dentoalveolar protrusion by applying different anchorage methods via
      three-dimensional model measurement. METHODS: A total of 46 patients with
      maxillary dentoalveolar protrusion treated with bilateral maxillary first
      premolar extractions and high anchorage were selected. The subjects were randomly
      divided into three groups according to the type of anchorage applied, which
      included implant, extraoral, and Nance arch anchorages. The maxillary dental
      models were made before treatment and after space closure of maxilla. The
      movements of the maxillary central incisors and first molars were measured via a
      three-dimensional model measurement, and the amounts of movement were compared
      among the three groups. RESULTS: The sagittal lingual movements of the maxillary
      central incisors were (-6.661 +/- 1.328), (-5.939 +/- 1.806), and (-5.788 +/-
      2.009) mm for the implant, extraoral, and Nance arch anchorage groups,
      respectively, with no significant difference among the three groups (P = 0.121).
      The corresponding vertical movements of the maxillary central incisors were
      (0.129 +/- 1.815) mm intrusion, and (-2.162 +/- 2.026), (-2.623 +/- 1.776) mm
      extrusion. Significant difference was found between the implant anchorage group
      and the other groups (P < 0.05). The corresponding sagittal mesial movements of
      the maxillary first molars were (0.608 +/- 1.045), (1.445 +/- 1.462), and (1.503
      +/- 0.945) mm. The corresponding vertical movements of the maxillary first molars
      were (0.720 +/- 0.805) mm intrusion, (0.076 +/- 0.986) mm intrusion, and (-0.072
      +/- 0.690) mm extrusion. Significant difference was found between the implant
      anchorage group and the other two groups (P < 0.05). In the transverse direction,
      the first molars all moved lingually with no significant difference among the
      three groups (P > 0.05). CONCLUSION: Implant anchorage may be superior in the
      vertical control of the maxillary incisors and in the sagittal, as well as in the
      vertical control of the maxillary molars, compared with the traditional
      anchorages during the treatment of patients with maxillary dentoalveolar
      protrusion.

PMID- 25872302
TI  - [Finite element analysis of periodontal tissue stress distribution of labial
      inverted impacted maxillary central incisor].
AB  - OBJECTIVE: This study aims to do the following: construct a three-dimensional
      finite element model of an labial inverted impacted maxillary central incisor and
      its supporting tissues, analyze stress distribution in the periodontal tissue
      when various tractions are exerted, and provide references for treating impacted
      maxillary central incisor. METHODS: A three-dimensional finite element model
      oflabial inverted impacted maxillary central incisor and its periodontal tissues
      was established using Mimics 10.01 and Ansys 14.0 software based on original cone
      beam computed tomography (CBCT) data. Various traction values (20, 30, 40, 50,
      60, and 70 g) were exerted on the incisal margin in the direction perpendicular
      to the impacted tooth. Different Von Mises stress values were determined.
      RESULTS: Stress distribution on the periodontal ligament increased with traction
      size. When 30 g traction was exerted on the labial inverted impacted maxillary
      central incisor, the Von Mises stress was 24 919.0 Pa, which was within the range
      of the optimum force and close to its maximum value. CONCLUSION: The optimum
      traction for early orthodontic treatment of labial inverted impacted maxillary
      central incisor is nearly 30 g.

PMID- 25872303
TI  - [Reconstruction and measurement of a digital dental model using grating
      projection and reverse engineering].
AB  - OBJECTIVE: This work lays the foundation for establishing a digital model
      database with normal occlusion. A digital dental cast is acquired through grating
      projection, and model features are measured through reverse engineering. METHODS:
      The grating projection system controlled by a computer was projected onto the
      surface of a normal dental model. Three-dimensional contour data were obtained
      through multi-angle shooting. A three-dimensional model was constructed, and the
      model features were analyzed by using reverse engineering. The digital model was
      compared with the plaster model to determine the accuracy of the measurement
      system. RESULTS: The structure of three-dimensional reconstruction model was
      clear. The digital models of two measurements exhibited no significant difference
      (P > 0.05). When digital and plaster models were measured, we found that the
      crown length and arch width were not statistically different (P > 0.05), whereas
      the difference between the crown width and arch length was statistically
      significant (P < 0.05). CONCLUSION: The reconstruction of a digital model by
      using the grating projection technique and reverse engineering can be used for
      dental model measurement in clinic al and scientific research and can provide a
      scientific method for establishing a digital model database with normal
      occlusion.

PMID- 25872304
TI  - [Effects of mineral trioxide aggregate on the proliferation and differentiation
      of human pulp cells from primary and permanent teeth].
AB  - OBJECTIVE: This study aims to investigate the effects of mineral trioxide
      aggregate (MTA) and calcium hydroxide on proliferation and differentiation of
      human pulp cells from primary and permanent teeth. METHODS: Cell proliferation
      was detected by methyl thiazolyl tetrazolium (MTT) assay. The mRNA expression
      levels of dentinogenesis-related factors, including alkaline phosphatase (ALP)
      and dentin sialophosphoprotein (DSPP), and odontoclastogenesis-related factors,
      such as osteo- protegerin (OPG) and receptor activator of NF-kappaB ligand
      (RANKL), were determined by real time polymerase chain reac- tion (PCR). RESULTS:
      Primary and permanent pulp cells treated with calcium hydroxide exhibited
      significantly lower proli- feration rates than the control cells (P<0.01). By
      contrast, the MTA-treated group showed significantly higher proliferation rates
      than the control group (P<0.01). Real time PCR results showed that calcium
      hydroxide-treated primary pulp cells exhi- bited significantly decreased ALP,
      DSPP, and OPG expression compared with the control group (P<0.01). Conversely,
      the MTA-treated group displayed significantly increased ALP, DSPP, and OPG
      expression (P<0.01). Calcium hydroxide-treated primary pulp cells also exhibited
      significantly upregulated RANKL expression (P < 0.01); by contrast, MTA-treated
      cells did not show any change in RANKL expression (P>0.05). Likewise, MTA-treated
      permanent pulp cells showed significantly upregulated ALP and DSPP expression (P
      < 0.01). However, the calcium hydroxide-treated group remained almost the same as
      the control group (P > 0.05). Neither MTA nor calcium hydroxide affected OPG and
      RANKL expression in per- manent pulp cells (P > 0.05). CONCLUSION: MTA is more
      suitable as a pulp-capping agent, particularly in primary teeth, than calcium
      hydroxide.

PMID- 25872305
TI  - [Effects of growth stages and pH value on the expression of autolytic enzyme atIS
      gene of Streptococcus gordonii].
AB  - OBJECTIVE: This study aimed to detect the difference in the expression levels of
      autolysin atIS gene of Streptococcus gordonii (S. gordonii) at different growth
      stages and pH values, as well as to analyze the factors regulating atlS gene
      expression in S. gordonii. METHODS: S. gordonii wild strains (ATCC 35105) were
      collected at different growth stages (early exponential phase, mid-exponential
      phase, late exponential stage, and platform stage) and pH values (pH 7 and pH
      5.5), and total RNA was extracted by using a conventional method. Fluorescence
      quantitative polymerase chain reaction (FQ-PCR) was used to measure the relative
      mRNA expression of atlS gene, with bacterial 16S rRNA as internal reference, for
      a comparison of the mRNA levels of atlS gene expression in S.gordonii at
      different growth stages and pH values. RESULTS: FQ-PCR results showed that atlS
      gene expression increased with gradually increasing growth stage under neutral
      conditions and was higher than that under acidic conditions (P < 0.05).
      CONCLUSION: The atlS gene expression in S. gordonii is influenced by growth stage
      and pH value factors.

PMID- 25872306
TI  - [Effects of concentrated growth factor extract on the proliferation and
      differentiation of MC3T3-E1 cells attached to titanium surfaces].
AB  - OBJECTIVE: To evaluate the effect of concentrated growth factor extract (CGFe) on
      the proliferation and differentiation of MC3T3-E1 osteoblasts attached to
      sandblasted and acid etched titanium surfaces. METHODS: Trials were divided into
      experimental and control groups. The experimental group used a-MEM that contained
      CGFe (10% FBS), whereas the control group only used a-MEM (10% FBS). MTT assay
      was employed to detect the number of osteoblasts on the first, third, and fifth
      days. Alkaline phosphatase (ALP) activity and scanning electron microscope (SEM)
      were used to detect the osteoblast differentiations on the third and fifth days
      and to observe the osteoblast extensions on titanium surfaces for 12 h,
      respectively. Meanwhile, the levels of the osteogenetic biomarkers Runt-related
      transcription factor-2 (Runx2) and Osterix (Osx) on the third and seventh days
      were quantified via real-time polymerase chain reaction (PCR). RESULTS: MTT assay
      indicated that on the first, third, and fifth days, the absorbance in the
      experimental group significantly increased than that in the control group (P <
      0.05). ALP activity: on the third and fifth days, the absorbance of the
      experimental group was significantly higher than that of the control group (P <
      0.05). SEM: at 12 h, the extension of the experimental group cells was larger
      than that of the control group. Real-time PCR: given the standardization in the
      group, the gene expression level of the control group on the third day was 1, and
      the Runx2 and Osx gene expressions in the experimental group were larger than
      those of the con- trol group. CONCLUSION: CGFe can efficiently stimulate the
      proliferation, differentiation and extension of MC3T3-E1 cells.

PMID- 25872307
TI  - [Colonization of Porphyromonas endodontalis in primary and secondary endodontic
      infections].
AB  - OBJECTIVE: This study aims to assess and compare the prevalence of Porphyromonas
      endodontalis (P. endodontalis) in root canals associated with primary and
      secondary endodontic infections by using 16s rDNA PCR and real-time fluorescence
      quantitative polymerase chain reaction (RTFQ-PCR). METHODS: A total of 120 adult
      patients with one radiographically documented periapical lesion were included.
      Sixty teeth presented with primary endodontic infections and 60 with secondary
      endodontic infections requiring retreatment. P. endodontalis was identified by
      using 16s rDNA PCR techniques. The positive DNA expression of P. endodontalis in
      two types of infected root canals were quantitatively compared by using SYBR
      GREEN I RTFQ-PCR. RESULTS: The prevalence of P. endodontalis in the root canals
      with primary endodontic infections was significantly higher than that in root
      canals with secondary endodontic infections (P = 0.001). However, RTFQ-PCR
      results showed no significant difference in DNA expression quantities between the
      primary and secondary endodontic infections root canals (P = 0.303). CONCLUSION:
      P. endodontalis is more highly associated with root canals having primary
      endodontic infections, although P. endodontalis colonize in both root canals with
      primary and secondary chronic apical periodontitis.

PMID- 25872308
TI  - [Research progress on the risk factors of geographic tongue].
AB  - Geographic tongue, also called benign migratory glossitis, is a common and
      superficial benign inflammatory disorder that affects the tongue epithelium. The
      majority of geographic tongue lesions typically manifest as irregular central
      erythematous patches. These lesions, which are caused by the loss of filiform
      papillae, are defined by an elevated whitish band-like border that can change
      location, size, and pattern over a period of time. Histological observations of
      the oral mucosa affected by geographic tongue revealed nonspecific inflammation.
      Some reports described cases of migratory stomatitis, wherein lesions
      simultaneously manifested on the extra lingual oral mucosa. This condition is
      also called ectopic geographic tongue, which is clinically and histologically
      similar to the type normally confined to the tongue. In most cases, patients are
      asymptomatic and do not require treatment. The condition may spontaneously
      exhibit periods of remission and exacerbation with good prognosis. The specific
      etiology of geographic tongue remains unknown. Geographic tongue is age-related
      and is prevalent among young individuals. Various etiological factors that have
      been suggested in literature include immunological factors, genetic factors,
      atopic or allergic tendency, emotional stress, tobacco consumption, hormonal
      disturbances, and zinc deficiency. Geographic tongue may coexist with other
      disorders, such as fissured tongue, psoriasis, diabetes mellitus, gastroin-
      testinal diseases, burning mouth syndrome, and Down syndrome. Experts currently
      disagree on whether geographic tongue is an oral manifestation of psoriasis.
      Moreover, some scholars suggest that geographic tongue is a prestage of fissured
      tongue. The objective of this review is to summarize current research on risk
      factors of geographic tongue.

PMID- 25872309
TI  - [Autophagy and its relationship with tumor proliferation, invasion, and
      treatment].
AB  - Autophagy is a highly conservative biological behavior in eukaryotic cells. This
      dynamic process involves "wrapping" cytoplasmic components and combining with
      lysosomes in cells for catabolism. The catabolic effect of autophagy can
      eliminate toxic substances in cells, maintain homeostasis in the intracellular
      environment, and produce small molecules, such as amino acids, which nourish
      cells, thereby allowing them to survive. Autophagy can inhibit the occurrence of
      tumors by maintaining homeostasis in the intracellular environment. However, it
      can promote the proliferation, invasion, and metastasis of malignant tumor cells.
      Autophagy can regulate the microenvironment of tumor cells and has an important
      role in a series of processes, such as anoikis, tumor dormancy, and epithelial
      mesenchymal transition.

PMID- 25872310
TI  - [Soft tissue chondrosarcoma occurred in the left parotid region: a case report].
AB  - Chondrosarcoma is extremely rare in maxillofacial soft tissue. A case diagnosed
      as well-differentiated chon- drosarcoma in the left parotid region was reported.
      The clinic pathological features, diagnosis, treatment, and prognosis were
      discussed with the literature review.

PMID- 25872311
TI  - [Myeloid sarcoma occurring in the gingiva: a case report].
AB  - Myeloid sarcoma (MS) is a localized extramedullary mass of immature granulocytic
      cells. MS may be found in any location, but intraoral occurrence is rare. This
      report presents a case of MS in the gingiva.

PMID- 25872312
TI  - [We are expanding the topic spectrum of the journal].

PMID- 25872313
TI  - [On the road to a new humanity: the reception of psychoanalysis in the early
      Kinderladen movement].
AB  - In the late 1960s a group of students in West Germany founded the so-called
      Kinderladen (day care centers) in order to experiment with new forms of early
      childhood education. Members of the early Kinderladen movement in particular
      pursued a radically utopian approach that, they hoped, would engender new human
      beings. With the aid of psychoanalytic writings, especially those of Wilhelm
      Reich, they sought to create subjects that would overcome repressive bourgeois
      norms and live out their sexuality freely. This reliance on Reich entailed a new
      interpretation of the "base", as psychoanalytic drive theory supplanted Marxist
      theory. As such, the early Kinderladen ac- tivists regarded the "basis" of
      society in biological, psychological, and pedagogic rather than economic terms.

PMID- 25872314
TI  - [Hedonism and revolution. The reception of psychoanalysis in the Berlin student
      movement in the 1960s].
AB  - The article takes hedonism and revolution as a vantage point to discuss the
      Kommune 2, an experiment in collective living, the anti-authoritarian
      kindergardens for the under-fives, and, last but not least, a speech in 1968 that
      spurred the women's movement in Western Germany. The author's interest is on the
      materials documenting how the Berlin student movement saw psychoanalysis: One
      point was that the pleasure principle should replace the reality principle for
      the sake of humankind, another that the authoritarian character structure has its
      roots in the denial of sexuality. Kindergarden children supposedly need "de
      individualized identification" to develop ego-strength, when boys and girls
      differ in their superego organization. An important accomplishment was a group
      analysis conducted without an analyst, an experiment that worked amazingly well
      in the Kommune 2. In all, these various experiments in emancipation, with
      psychoanalysis a guide to interpersonal understanding, may be deemed spectacular
      when their aftereffects on everyday life in Germany have been tremendous.

PMID- 25872315
TI  - [Psychoanalysis and the "Kinderladen" movement. A view on four projects].
AB  - Along with the reception of Critical Theory in the student movement of the 1960s,
      psychoanalytically influenced social criticism was spread by the SDS and the
      Argument-Club. This had prac tical consequences, especially for the development
      of antiauthoritarian education, often practiced by psychoanalytical autodidacts.
      The public outrage caused by antiauthoritarian education was overwhelming.
      Throughout the media excited reactions to "wild analysis" and "pedagogic
      experiments" were expressed. Conservative psychoanalysts, politicians and
      educationalists condemned each new approach to education and alleged oedipal
      acting-out and danger to the safety of the state and democracy. The emancipatory
      educational reform on the ground broke under the pressure of conservatism. Now is
      the time to draw a reasonable balance of the four year alliance between
      psychoanalysis and the student movement, especially as it seems that this
      alliance has not only a past but also a future.

PMID- 25872316
TI  - [Literary works play a great role in the "fiancee" letters].
AB  - Quoting from poems, novels, and dramas of the world literature, but also from
      popular or trivial contemporary works allowed Freud and Martha to express their
      own thoughts and feelings. They also at times identified with literary figures.
      The author describes which poets and writers they preferred and where they agreed
      or disagreed in their literary likings.

PMID- 25872317
TI  - [Eric D. Wittkower--a forgotten pioneer of psychosomatic medicine].
AB  - Eric D. Wittkower--a forgotten pioneer of psychosomatic medicine. Wittkower (1899
      1983) was not only a pioneer of psychosomatics, but also a psychoanalyst,
      psychiatrist, co-founder of the Canadian Psychoanalytic Society and major
      exponent of transcultural psychiatry. This article tries to retrace his early
      years and studies in Berlin by means of autobiographical notes and archival
      material in the Berlin university. Then it focuses on his research and
      specialisation as a doctor and lecturer of psychosomatic medicine until his
      forced emigration in 1933.

PMID- 25872318
TI  - [Letters to George Sylvester Viereck (1919-1936]. Published by Dominic Angeloch].

PMID- 25872319
TI  - ["Paper with sacred characters]." 2nd volume of bridal letters by Sigmund Freud
      and Martha Bernays].

PMID- 25872320
TI  - ["It is time for a new perspective on Abraham"].

PMID- 25872321
TI  - [The drama of psychoanalysis during the time of national socialism. On the
      Andreas Peglau book about Wilhelm Reich].

PMID- 25872322
TI  - Interaction between metabolic challenges and productivity in high yielding dairy
      cows.
AB  - The onset of lactation in modern dairy cows is characterized by a negative energy
      balance, due to a drastic increase in energy requirements for milk yield and a
      simultaneous depression in dry matter intake around parturition. Prioritization
      of milk yield over maternal body functions is a universal biological strategy in
      all lactating mammals to buffer the newborn's nutrition from fluctuations in the
      dam's energetic status. Consequently, in case of an energy deficiency, the dam
      will mobilize fat and protein reserves in order to safeguard milk yield. During
      decades of one-sided selection for milk yield, man has exploited the cow's
      potential to prioritize mammary energy supply without an equivalent progress in
      dry matter intake capacity. Consequently, genetic selection for milk yield has
      widened the gap between energy expenditure and energy intake, and has increased
      the cow's inclination to respond to energy deficiencies in the transition period
      by aggressive body tissue breakdown. Chronically elevated concentrations of non
      esterified fatty acids and ketone bodies have been demonstrated to affect
      multiple organ systems including the immune system, the reproductive axis and the
      liver and are, in contrast to absolute milk yield, closely and consistently
      related to the final incidence of reproductive disorders.

PMID- 25872323
TI  - Factors contributing to immunosuppression in the dairy cow during the
      periparturient period.
AB  - The transition from late gestation to early lactation results in dramatic
      physiological changes including metabolic changes and immunosuppression in the
      dairy cow. As a result, cows are at a high risk for disease during this time.
      Evidence supporting a link between metabolic status and naturally occurring
      immunosuppression is growing. This review focuses on the impacts of metabolic
      status, and the metabolites that characterize it, on the immune response of cows
      during the transition period. Glucose is the preferred fuel for immune cells and
      its low concentration during the transition period may partly explain the
      naturally occurring immunosuppression at this time. To our knowledge, ketones are
      not utilized by immune cells and primarily have been shown to inhibit the immune
      response when concentration is relatively high. The effect of fatty acids on the
      immune system response remains unclear. Evidence suggests that the type of fatty
      acid can either stimulate (i.e. saturated fatty acids) or inhibit (i.e.
      unsaturated fatty acids) the immune response. We have suggested that an index for
      physiological imbalance (PI), based on circulating metabolites that characterize
      metabolic status, directly relates to mechanisms associated with the development
      of disease and is superior to calculated energy balance and therefore is a better
      predictor of risk of disease. The usefulness of the PI index as a predictor of
      risk of disease and the mechanisms associated with the links between degree of PI
      and immunosuppression for dairy cows during the transition period warrants
      further investigation.

PMID- 25872324
TI  - Subacute ruminal acidosis (SARA) challenge, ruminal condition and cellular
      immunity in cattle.
AB  - Subacute ruminal acidosis (SARA) is characterized by repeated bouts of low
      ruminal pH. Cows with SARA often develop complications or other diseases, and
      associate physiologically with immunosuppression and inflammation. Ruminal free
      lipopolysaccharide (LPS) increases during SARA and translocates into the blood
      circulation activating an inflammatory response. Ruminal fermentation and
      cellular immunity are encouraged by supplementing hay with calf starter during
      weaning. SARA calves given a 5-day repeated administration of a bacteria-based
      probiotic had stable ruminal pH levels (6.6-6.8). The repeated administration of
      probiotics enhance cellular immune function and encourage recovery from diarrhea
      in pre-weaning calves. Furthermore, the ruminal fermentation could guard against
      acute and short-term feeding changes, and changes in the rumen microbial
      composition of SARA cattle might occur following changes in ruminal pH. The
      repeated bouts of low ruminal pH in SARA cattle might be associated with
      depression of cellular immunity.

PMID- 25872325
TI  - Genetic selection of cattle for improved immunity and health.
AB  - The immune system is a sensing structure composed of tissues and molecules that
      are well integrated with the neuroendocrine system. This integrate system ensures
      non-self from self-discrimination. In this capacity the immune system provides
      detection and protection from a wide range of pathogens. In mammals, the immune
      system is regulated by several thousand genes (8-9% of the genome) which indicate
      its high genetic priority as a critical fitness trait providing survival of the
      species. Identifying and selectively breeding livestock with the inherent ability
      to make superior immune responses can reduce disease occurrence, improve milk
      quality and increase farm profitability. Healthier animals also may be expected
      to demonstrate improvements in other traits, including reproductive fitness.
      Using the University of Guelph's patented High Immune Response technology it is
      possible to classify animals as high, average, or low responders based on their
      genetic estimated breeding value for immune responsiveness. High responders have
      the inherent ability to produce more balanced and robust immune responses
      compared with average or low responders. High responders dairy cattle essentially
      have about one-half the disease occurrence of low responders, and can pass their
      superior immune response genes on to future generations thereby accumulating
      health benefits within the dairy herd.

PMID- 25872326
TI  - Nerve sparing radical hysterectomy in early stage cervical cancer. Latest
      developments and review of the literature.
AB  - BACKGROUND: Cervical cancer is the second most common malignancy of the female
      genital tract worldwide. Radical hysterectomy with pelvic lymphadenectomy
      exemplifies the treatment of choice for early stage disease, whereas even if it
      is performed by gynaecologist-oncologist, still has the drawback of significant
      postoperative morbidity, especially for urinary bladder function. Nerve-sparing
      radical hysterectomy (NSRH) is a technique in which the neural part of the
      cardinal ligament which encloses the inferior hypogastric plexus, as well as the
      bladder branch (distal part of the plexus), remains intact. By this way, the
      bladder's innervation is safe and its functional recovery is more rapid. There is
      sufficient data to support the feasibility of the technique via laparotomy and
      laparoscopy, as well as the effectiveness related to the postoperative bladder
      dysfunction compared to conventional radical hysterectomy. On the other hand, the
      evidence related to survival outcomes is weak and derives from non-randomized
      trials. However, the low rate of local relapses after NSRH in early stage disease
      (IA2-IB1) with tumor diameter less than two cm makes the procedure suitable for
      this group of patients. CONCLUSION: According to the current evidence NSRH seems
      to be a suitable technique for gynaecologist-oncologist familiar with the method
      in early stage cervical cancer. It is a technique which improves significantly
      postoperative bladder recovery and the patients' quality of life (QoL), without
      compromising the oncological standard.

PMID- 25872327
TI  - Sentinel node mapping with radiotracer alone in vulvar cancer: a five year single
      centre experience and literature review.
AB  - PURPOSE OF INVESTIGATION: The pathologic status of lymph node represents the most
      important prognostic factor in vulvar cancer patients, but a complete groin
      dissection is associated with high post-operative morbidity. Sentinel lymph node
      (SLN) could be representative of the totality of regional lymph nodes and
      consequently its biopsy might have a significant impact on clinical management in
      vulvar cancer patients. MATERIALS AND METHODS: From January 2006 to December 2010
      45 patients with vulvar carcinoma are evaluated. Preoperative lymphatic mapping
      with technetium-99m-labeled nanocolloid was performed in all patients, followed
      by radioguided intraoperative detection. The detection rate is 100% of patients.
      All the SLNs were dissected separately for histopathological evaluation and a
      routine inguinofemoral lymphadenectomy was performed. RESULTS: Nine patients had
      positive SLNs. In the remaining 36 patients with negative SLNs, one of them
      showed positive non-SLNs at histological examination. It was the only false
      negative case in the present series. CONCLUSIONS: Based on literature review,
      lymphoscintigraphy and sentinel node biopsy under gamma-detecting probe guidance
      offer a reliable and careful method to identify sentinel node in early vulvar
      cancer. Taking certain guidelines, SLN biopsy seems to be a safe alternative to
      inguinofemoral node dissection in order to reduce morbidity of surgical
      treatment.

PMID- 25872328
TI  - MicroRNA signatures of platinum-resistance in ovarian cancer.
AB  - OBJECTIVES: The authors utilized a microRNA (miRNA) array to compare the
      differentially expressed miRNAs in platinum-resistant associated ovarian cancer
      cells. MATERIALS AND METHODS: The differential expression of microRNA between
      COC1 (DDP-sensitive) and platinum-resistant COC1/DDP (DDP-resistant) tumor cell
      lines was determined using microarray. Expression levels were further validated
      by real-time quantitive polymerase chain reaction (qRT-PCR). RESULTS: The authors
      identified that several miRNAs are altered in collected 86 samples of human
      ovarian cancer cell-lines, with four significantly deregulated miRNAs and 13
      upregulated miRNAs. Of which, miR-141-3p was the most differentially expressed
      miRNA between COC1 group (1.7833 +/- 0.7213) and COC1/DDP group (14.0433 +/-
      4.4895) (p < 0.05). Additionally, the product curve of PCR amplification
      indicated that miR-141-3p had a significant higher expression level in
      chemotherapy resistant group (n = 20) rather than in chemotherapy sensitive group
      (n = 20) (9.56 +/- 1.04 vs. 1.59 +/- 0.91, p < 0.05). CONCLUSIONS: The present
      results suggest that miR-141-3p might be used as a therapeutic target to modulate
      platinum-based chemotherapy and as a biomarker to predict chemotherapy response.

PMID- 25872329
TI  - Prevalence of endometriosis in epithelial ovarian cancer. Analysis of the
      associated clinical features and study on molecular mechanisms involved in the
      possible causality.
AB  - PURPOSE OF INVESTIGATION: To determine the prevalence of endometriosis in
      patients with epithelial ovarian cancer and explore the differences between women
      with endometrioid and clear-cell histologic subtypes with and without associated
      endometriosis. MATERIALS AND METHODS: The medical charts of 496 patients with
      epithelial ovarian cancer at the Hospital Virgin de la Arrixaca (Murcia, Spain)
      between 1971 and 2010 were reviewed. RESULTS: Endometriosis was present in 27
      (5.4%) of the 496 cases (p < 0001), and was associated with the endometrioid
      histotype in 13/45 cases (29%) and with the clear cell histotype in 7/22 (32%).
      The prevalence of an association with endometriosis according to histologic type
      was 28.8% (13/45) for endometrioid carcinoma and 31.8% (7/22) for clear-cell
      carcinoma. CONCLUSION: Both endometrioid and clear-cell ovarians tumours are
      associated with pelvic endometriosis. Patients with endometiosis associated
      ovarian cancer differ from non-endometiosis associated ovarian cancer in their
      clinical characteristics.

PMID- 25872330
TI  - Laparoscopic ovarian transposition in young women with cervical squamous cell
      carcinoma treated by primary pelvic irradiation.
AB  - OBJECTIVE: To report the authors' experience with laparoscopic ovarian
      transposition and ovarian function preservation in young women with cervical
      squamous cell carcinoma treated by primary pelvic irradiation. MATERIALS AND
      METHODS: Twenty-seven premenopausal patients were treated with radiotherapy for a
      cervical squamous cell carcinoma. Laparoscopic ovarian transposition to paracolic
      gutters with uterine conservation with pelvic common iliac lymph node and para
      aortic lymph node sampling were performed in ten patients at the same time of
      laparoscopic ovarian transposition. Preservation of ovarian function was assessed
      by patients' symptoms and serum follicle-stimulating hormone level. RESULTS:
      Bilateral or unilateral laparoscopic ovarian transposition was performed in 27
      patients: 22 cases Stage IIB, one case Stage IIIA, and four cases Stage IIIB. No
      immediate intraoperative or postoperative complications were observed. Two of the
      ten patients were confirmed by lymph node metastases. One patient was lost to
      follow-up. Ovarian preservation was achieved in 18 (69.2%) of 26 patients. No
      patient was detected with ovarian metastasis at follow-up. CONCLUSIONS:
      Laparoscopic ovarian transposition is a safe and effective procedure for
      preserving ovarian function. This procedure may be considered in premenopausal
      women who need to undergo pelvic irradiation for cervical squamous cell
      carcinoma, especially for those less than 40 years of age. Otherwise, para-aortic
      lymph node or common iliac lymph nods sampling at the same time of laparoscopic
      ovarian transposition may preferably guide radiation therapy.

PMID- 25872331
TI  - The prognostic significance of pretreatment [18F]FDG-PET/CT imaging in patients
      with uterine cervical cancer: preliminary results.
AB  - PURPOSE OF INVESTIGATION: To evaluate the prognostic significance of positron
      emission tomography/computed tomography (PET/CT) in patients diagnosed with
      cervical cancer. MATERIALS AND METHODS: Patients with cervical cancer in FIGO
      Stages IB1 to IVB were imaged with PET/CT prior to treatment during one of the
      staging work-ups. The patients were observed for a median of 31.4 months (range,
      six to 89 months) after the initial treatment. The standardized uptake value
      (SUV) max of the primary cervical tumor mass was compared with the prognostic
      factors. RESULTs: A total of 81 patients who were primarily treated with radical
      hysterectomy (RH, n = 45) or concurrent chemoradiation (CCRT, n = 36) were
      analyzed. Multivariate analysis indicated that larger tumor size (> 4 cm, OR
      8.694, 95% CI, 1.638-46.146), deep stromal invasion (>= 1 cm, OR 7.249, 95% CI,
      1.141-46.039) by the primary tumor, and pathologically confirmed pelvic lymph
      node involvement (positive, OR 14.586, 95% CI, 2.072-102.674) were significantly
      associated with recurrence after treatment. However, pretreatment SUVmax was not
      a significant independent predictor of disease recurrence (OR 1.058, 95% CI,
      0.255-4.398). CONCLUSION: [18F]Fluorodeoxyglucose (FDG) uptake by the primary
      tumor showed a significant association with several risk factors that have been
      identified as treatment predictors. However, a high pretreatment SUVmax was not
      predictive of recurrence in uter- ine cervical cancer patients.

PMID- 25872332
TI  - The role of mTOR signaling pathway in premalignant and malignant cervical
      lesions.
AB  - PURPOSE OF THE STUDY: Aberrant activation of the Akt/mTOR/pS6 signaling pathway
      has been identified in various types of cancer and is under investigation in
      cervical cancer. The purpose of this study was to assess the expression of the
      phosphorylated/activated forms of Akt (upstream molecule), 4E-BP1 and pS6
      (downstream molecules) in biopsy samples of cervical low grade squamous
      intraepithelial lesions (LSIL), high grade squamous intraepithelial lesions
      (HSIL), and squamous cell carcinoma (Ca) compared to normal cervical epithelium.
      MATERIAL AND METHODS: The study included 38 cases diagnosed as LSIL, 31 cases as
      HSIL, 29 cases as Ca, and eight control cases from normal cervix.
      Immunohistochemistry was used to assess the expression of pAkt, p4E-BP1 and pS6.
      RESULTS: Statistical analysis revealed significant differences between HSIL and
      Ca groups compared to controls regarding intensity, positivity, and total scores
      for all three molecules (p < 0.001). A trend for higher expression with
      increasing grade of dysplasia was demonstrated. CONCLUSION: These results
      strongly support the view that the mTOR signaling pathway is involved in cervical
      carcinogenesis.

PMID- 25872333
TI  - Effect of lentivirus mediated cyclooxygenase-2 gene shorthairpinRNA on
      invasiveness of endometrial carcinoma.
AB  - OBJECTIVE: This study aims to explore the effects of lentivirus mediated
      cyclooxygenase-2 gene shorthairpinRNA (COX-2-shRNA) on invasiveness of
      endometrial carcinoma HEC-1B cells. MATERIALS AND METHODS: Double-stranded DNA
      oligonucleotide of COX-2-shRNA was designed and synthesized, and the recombinant
      lentiviral vector COX-2-ShRNA (LV-COX-2-ShRNA) was constructed. LV-COX-2-ShRNA,
      pHelper 1, and pHelper 2 were transferred into 293T cells, followed by lentiviral
      packaging. The virus titer was tested according to expression level of GFP in
      293T cells. HEC-1B cells were infected with recombinant lentivirus. The silencing
      of COX-2 gene was assessed by real-time PCR and western-blot, and the in vivo
      invasiveness of HEC-1B cells was analyzed by transwell invasion assay. RESULTS:
      Recombinant lentiviral vector expressing siRNA targeting COX-2 gene was
      successfully constructed to harvest the recombinant lentivirus with the
      concentrated virus suspension titer of 5 x 10(7)Tu/ml. Compared with control
      group, the inhibitory rate of COX-2 expression in HEC-1B cells in siRNA group
      were 61.87% and 67.48% at mRNA and protein level, respectively. The mean number
      of cells penetrating matrigel was 16.6, which was significantly less than the
      control group 50.2 and non-specific siRNA infection group 47.2, the invasion
      inhibition rate being 64.8% (p < 0.01). CONCLUSION: RNA interference can inhibit
      the invasiveness of HEC-in cells.

PMID- 25872334
TI  - Primary peritoneal cancer: study of 14 cases and comparison with epithelial
      ovarian cancer.
AB  - PURPOSE OF INVESTIGATION: Primary peritoneal carcinoma (PPC) is histologically
      similar to ovarian serous carcinoma, but its biochemical features remain obscure.
      The authors investigated and compared clinical findings, treatments, and outcomes
      of patients with PPS and those with epithelial ovarian cancer (EOC) patients.
      MATERIALS AND METHODS: The authors retrospectively reviewed data from 14 patients
      with PPC and 219 patients with EOC treated at the present hospital from January
      2005 to December 2012, including demographic data, pathologic findings,
      treatments, and outcomes. RESULTS: Patients with PPC were significantly older
      (62.6 +/- 8.4 years) than those with EOC (56.3 +/- 11.3 years) (p = 0.045). There
      was no significant difference in serum CA-125 levels. The five-year survival
      rates did not differ significantly between patients with PPC (61.1%) and those
      with EOC (60.3%; p = 0.78); nor between patients with PPC and those with Stage
      III serous EOC (43.8%; p = 0.40). CONCLUSIONS: Treatment strategies for EOC
      applied to PPC apparently led to similar survival patterns among the two patient
      groups. Cytoreductive surgery combined with pre/postoperative platinum-containing
      chemotherapy may be effective for PPC patients.

PMID- 25872335
TI  - Combination therapy of liposomal paclitaxel and cisplatin as neoadjuvant
      chemotherapy in locally advanced cervical cancer.
AB  - OBJECTIVES: To investigate the efficacy and toxicities of combination therapy of
      liposomal paclitaxel and cisplatin as neoadjuvant chemotherapy (NACT) in locally
      advanced cervical cancer. MATERIALS AND METHODS: The authors retrospectively
      reviewed the clinical records of patients with cervical cancer who received NACT
      with liposomal paclitaxel and cisplatin at Sun Yat-sen University Cancer Center
      from April 1, 2008 to December 31, 2012. Liposomal paclitaxel and cisplatin was
      administrated intravenously at a dose of 175 mg/m2 and 75 mg/m2, respectively.
      RESULTS: The total response rate was 86.1% (62/72) including a complete response
      and partial response rate of 27.8% (20/72) and 58.3% (42/72), respectively.
      Stable disease was observed in 12.5% (9/72) of patients and progressive disease
      in 1.4% (1/72). Hematological toxicities were the major dose-limiting toxicities.
      Grade 3/4 neutropenia and anemia developed in 18.1% (13/72) and 6.9% (5/72) of
      patients, respectively. Peripheral neuropathy occurred in 6.9% (5/72) of patients
      (all grade 1). CONCLUSION: The study findings support further evaluation of
      liposomal paclitaxel with cisplatin as an additional chemotherapy regimen which
      may be efficacious and tolerable in the NACT of cervical cancer.

PMID- 25872336
TI  - Pyometra in elderly post-menopausal women: a sign of malignity.
AB  - PURPOSE: To describe the clinical and histopathological characteristics of 12
      patients with pyometra and highlight the increased incidence of gynecological
      malignancy in these patients. MATERIALS AND METHODS: The authors examined the
      medical records of 12 patients with pyometra, who were treated between 2009 and
      2013. RESULTS: All patients were post-menopausal, and their mean age was 70.83 +/
      6.978 years (min = 61, max = 82). To remove purulent fluid via dilation and
      because of the probability of malignancy, three patients (25%) underwent cervical
      biopsy and endometrial curettage; the other nine patients (75%) underwent
      curettage alone, with suitable antibiotic therapy. Of the 12 patients, nine (75%)
      had gynecologic malignancy [(endometrial cancer, n = 5, 41.6%), (cervical cancer,
      n = 3, 25%), (uterine leiomyosarcoma, n = 1, 8.3%)]. In three (25%) patients, the
      cause of pyometra was benign pathologies, among which the most common were
      leiomyomas (n = 2, 66.6%). CONCLUSION: Pyometra diagnosed during the post
      menopausal period should be considered a complication caused by gynecological
      malignancy until proven otherwise.

PMID- 25872337
TI  - Expressions of survivin, P16(INK4a), COX-2, and Ki-67 in cervical cancer
      progression reveal the potential clinical application.
AB  - PURPOSE OF INVESTIGATION: To explore the significance of survivin, P16(INK4a),
      COX-2, and Ki-67 expressions for prediction of cervical cancer progression.
      MATERIALS AND METHODS: A retrospective study was performed in 129 cases including
      24 squamous carcinoma of the cervix (SCC), 70 cervical intraepithelial neoplasias
      (CIN), 15 cervical condyloma acuminatum (CCA), ten chronic cervicitis (CC), and
      ten normal cervix (NC). Protein expressions were evaluated using
      immunohistochemistry. RESULTS: Survivin, P16(INK4a); COX-2, and Ki-67 were highly
      expressed in SCC and CIN compared with others. Their expression rates were
      gradually increased in CIN I, CIN II, CIN III, and SCC groups, showing 72.00%,
      88.00%, 90.00%, and 95.83% for P16(INK4a), 68.00%, 84.00%, 95.00% and 100.00% for
      COX-2, 76.00%, 96.00%, 100.00%, and 100.00 for Ki-67, respectively. There were
      significant correlations between survivin and P16(INK4a), COX-2, Ki-67, as well
      as P16(INK4a) and Ki-67. CONCLUSION: Survivin, P16(INK4a), COX-2 and Ki-67 play
      critical roles for development and progression of cervical cancer.

PMID- 25872338
TI  - Epidemiology of ovarian cancer in North Sardinia, Italy, during the period 1992
      2010.
AB  - INTRODUCTION: The aim of this study was to analyze and describe the incidence and
      mortality trends of ovarian cancer in North Sardinia, Italy, in the period 1992
      2010. MATERIALS AND METHODS: Data were obtained from the tumor registry of
      Sassari province which makes part of a wider registry web, coordinated today by
      the Italian Association for Tumor Registries. RESULTS: The overall number of
      ovarian cancer cases registered in the period under investigation was 600. The
      mean age of the patients was 62 years. The standardized incidence and mortality
      rates were 11.2/100,000 and 5.1/100,000 respectively. A substantially stable
      trend in incidence and mortality of ovarian cancer was evidenced. Relative
      survival at five years from diagnosis was 44.2%. CONCLUSIONS: The incidence and
      mortality trends of ovarian cancer in North Sardinia remained relatively stable
      in the last decades, while prognosis remains relatively poor.

PMID- 25872339
TI  - Prevalence of human papillomavirus and the correlation of HPV infection with
      cervical disease in Weihai, China.
AB  - OBJECTIVE: This study investigates the human papillomavirus (HPV) infection rate
      in female genital tracts, as well as the HPV genotype distribution and HPV
      correlation with cervical disease in Weihai, Shandong Province, China. MATERIALS
      AND METHODS: A random sample of 9,460 volunteers was simultaneously screened
      using gene chips and examined by ThinPrep liquid-based cytology test (TCT).
      Cervical biopsy samples were collected from women with positive HPV-DNA and
      abnormal TCT for pathological diagnosis. RESULTS: The overall HPV prevalence was
      6.93% (656 of 9,460). A total of 753 subjects were infected with HPV subtypes
      (including multiple HPV infections). Of those with infections, 688 were infected
      with high-risk (HR) types (91.37%), and 65 were infected with low-risk subtypes
      (8.63%). The single-infection rate was 63.1%.The prevalence rates of HPV in women
      aged 20 to 39 years and 40 to 59 years were 7.29% and 6.71%, respectively. The
      most common genotype was HPV16. The HR genotypes were associated with cervical
      diseases such as atypical squamous cells of undetermined significance (ASCUS)
      (37.9%), atypical squamous cells high grade (ASC-H) (42.5%), low grade squamous
      intraepithelial lesion (LSIL) (50%), and high grade squamous intraepithelial
      lesion HSIL (66.7%). Cervical biopsy results show that the HPV detection rate
      increased in the following biopsy samples: cervical intraepithelial neoplasia
      (CIN) I (74.11%), CIN II (84.31%), CIN III (90.32%), and squamous-cell carcinoma
      (SCC) (100%). CONCLUSIONS: The HPV infection rate with associated cervical
      disease in Weihai is equal to those in foreign countries but is lower than the
      average rate in China. The prevalence of HPV was higher in young people. The most
      common HPV genotype was 16, followed by 52 and 58. HR HPV is the most probable
      infection factor for cervical diseases.

PMID- 25872340
TI  - Correlation analysis of hormone receptors and the expressions of HER-2 and Ki-67
      in breast cancer.
AB  - OBJECTIVE: This study aims to investigate the correlation and clinical
      significance of hormone receptors and the expressions of HER-2 and Ki-67 in
      breast cancer primary lesions and lymph node metastatic tissues. METHODS: 83
      cases were studied, who were performed breast cancer surgeries and confirmed the
      ipsilateral axillary lymph node metastasis by the postoperative pathological
      diagnosis. Immunohistochemical method was used to simultaneously detect the
      expressions of ER, PR, HER-2 and Ki-67 in the primary lesions and lymph node
      metastases. RESULTS: ER exhibited the expression concordance rate as 85.5% in
      primary lesions and metastases, with significant difference (P = 0.039); the
      expression concordance rates of PR and HER-2 in primary lesions and metastases
      were 90.4% and 89.2%, respectively, without significant difference (P = 0.289,
      0.180); between the Ki-67-highly-expressed primary lesions and Ki-67-lowly
      expressed metastases, the expressions of ER in primary lesions and metastases
      exhibited statistical significance, with P as 0.031. CONCLUSIONS: The primary
      lesions and lymph node metastases had higher consistency, while there was still
      about 10% patients showed differentiated expression. The simultaneous detection
      of breast cancer primary lesions and lymph node metastases was still very
      necessary.

PMID- 25872341
TI  - Leiomyosarcoma: a rare malignant transformation of a uterine leiomyoma.
AB  - The malignant transformation of a uterine leiomyoma is still debated and, if it
      occurs, it is very rare. The case of a patient affected by one small leiomyoma is
      described. Diagnosis was made postoperatively on histopathological examination.
      The case reported here is meant to underline the need to keep all uterine myomas
      in check since the transition into leiomyosarcomas (LMSs) may occur with an
      evolution over a time period which has not been established so far. Specific
      receptors for luteinizing hormone/human chorionic gonadotropin (LH/hCG) have also
      been identified in the myometrium of several animal species, including humans.
      Conventional LMSs express estrogen receptors (ER), progesterone receptors (PR),
      and androgen receptors (AR) in 30-40% of cases. In comparison with other more
      common uterine malignancies, uterine LMSs bear some resemblance to type 2
      endometrial carcinomas and high-grade serous carcinomas of ovary/fallopian tube
      origin, based on their genetic instability, frequent p53 abnormalities,
      aggressive behavior, and resistance to chemotherapy. It could be useful to
      understand with further researches if hormonal stimulation could be a
      contributing factor of uterine leiomyoma transformation into LMS. Until today the
      oncogenic mechanisms underlying the development of uterine LMSs remain elusive.

PMID- 25872342
TI  - Small cell carcinoma of the ovary of the hypercalcemic type (SCCOHT)--case
      report.
AB  - Small cell carcinoma of the ovary of the hypercalcemic type (SCCOHT) is a very
      rare malignant disease, seen mostly in young women, with a very poor prognosis.
      There is no standard treatment for patients with this disease and most literature
      is limited to short series or case reports. This report describes the case of a
      34-year-old woman with aggressive course of SCCOHT and poor outcome. What proved
      difficult was the process of establishing the diagnosis due to non-specific first
      symptoms of disease and consequently the combined treatment of surgery and
      chemotherapy with concurrent side effects.

PMID- 25872343
TI  - Endometrial cancer in a patient with rheumatoid arthritis.
AB  - BACKGROUND: Rheumatoid arthritis is a chronic, systemic, and autoimmune disease.
      In patients with rheumatoid arthritis, there is increased risk for site-specific
      malignancies. The authors present a case of endometrial cancer in a patient with
      rheumatoid arthritis and a review of the current literature. CASE: The patient, a
      60-year-old, postmenopausal Greek woman suffering from rheumatoid arthritis,
      presented with a complaint of abnormal uterine bleeding. She underwent total
      abdominal hysterectomy, bilateral salpingo-oophorectomy, and pelvic and para
      aortic lymphadenectomy. Histopathology revealed endometrial cancer. The final
      diagnosis was Stage Ib endometrial cancer endometrioid type. She underwent
      postoperative adjuvant radiotherapy. She remains without evidence of disease, 16
      months after initial surgery. CONCLUSION: Although the present patient was
      diagnosed at early-stage disease and remains well 16 months after initial
      surgery, she needs a multidisciplinary treatment approach in order to achieve
      prolonged survival.

PMID- 25872344
TI  - [The progress of TRP channels in structural studies].
AB  - Transient receptor potential (TRP) channels are a super-family of nonselective
      cation channels that play critical roles in the responses to various
      environmental changes and stimuli. Over the past 10 years much progress has been
      made in the structural studies of TRP channels. To date, the structures of 5 full
      length TRP channels and their 11 cytoplasmic domains have been determined. These
      structural insights enhance our understanding of TRP channel gating, assembly and
      regulation. In this review, the structures of TRP channels are summarized with an
      emphasis on the progress made during the last two years.

PMID- 25872345
TI  - [The function of ERalpha in male reproductive system].
AB  - Estrogen receptors (ERs), including two sub-types ERalpha and ERbeta, belong to
      the steroid hormone superfamily of nuclear receptors. ERalpha distributes in the
      male reproductive system and plays a crucial role in the regulation of male
      reproduction through estrogen-dependent and -independent ways. In this article,
      we mainly reviewed the molecular structure, mode of action and location of
      ERalpha in the male reproductive system, and explored the mechanism of ERalpha in
      regulating the male reproductive system by analyzing different animal models of
      disrupted ERalpha.

PMID- 25872347
TI  - [Advance in research of the endomiRNAs and cardiovascular disease].

PMID- 25872346
TI  - [Transient receptor potential (TRP) channels and cardiac fibrosis].

PMID- 25872348
TI  - [The histone deacetylase sirtuins modulate cell autophagy in cardiovascular
      diseases].

PMID- 25872349
TI  - [The research progress of RNA binding motif protein 3 biological function].

PMID- 25872350
TI  - [Advance in the researches of cystine-glutamate antiporter].

PMID- 25872351
TI  - [Nesfatin-1 and reproduction].

PMID- 25872352
TI  - [Research progress on structure and function of schizophrenia-associated gene
      Disc1 and its encoding protein].

PMID- 25872353
TI  - [SIRT6 and energy metabolism].

PMID- 25872354
TI  - [The role and mechanism of cannabinoid receptor 2 in the inflammatory diseases of
      digestive system].

PMID- 25872355
TI  - [The pathogenesis and prospects for targeted therapy of HMGB1 in sepsisthe].

PMID- 25872356
TI  - [Interactions between ECM and HSC cells in hepatic fibrosis].

PMID- 25872357
TI  - [Neurobiological mechanisms on drug relapse].

PMID- 25872358
TI  - [T-tubule remodeling and new therapeutic strategy in myocardium].

PMID- 25872359
TI  - [Recent progress in the therapeutic potential of endogenous neural stem cells].

PMID- 25872360
TI  - [Non-genomic progesterone actions in sperm].

PMID- 25872361
TI  - [How to establish the positioning system within brain: introduction of Nobel
      Prize in Physiology or Medicine 2014].

PMID- 25872362
TI  - Hearing less.

PMID- 25872363
TI  - Age and wisdom 6 challenges to diabetes care as you grow older (and how to
      overcome them).

PMID- 25872364
TI  - Protect and serve. An FBI special agent with diabetes proves perseverance pays
      off.

PMID- 25872365
TI  - Salute to health. The VA's focus on veterans' diabetes care.
AB  - When diabetes advocates talk about groups of people at higher risk for the
      disease, they usually mention certain racial and ethnic groups. They might bring
      up age or obesity as risk factors. But veterans span all demographics and, as a
      group, nearly a quarter live with diabetes. The U.S. Department of Veterans
      Affairs (VA) reports that nearly one in four men and women (24 percent) who
      served their country have diabetes. That's much higher than the 9 percent of all
      Americans who have diabetes.

PMID- 25872366
TI  - Trial by science. The basics of clinical research.

PMID- 25872367
TI  - Medals of resilience. Awards honor those living with insulin-dependent diabetes
      for decades.

PMID- 25872368
TI  - Pots of gold.

PMID- 25872369
TI  - Young at heart. For people with type 2 diabetes, cardiovascular disease is enemy
      No. 1.

PMID- 25872370
TI  - [Effect of heat shock on cells of phytopathogenic mycoplasma Acholeplasma
      laidlawii PG-8A].
AB  - Heat shock caused a more active formation of the "dormant" forms (minibodies), as
      well as increased production of extracellular membrane vesicles by Acholeplasma
      laidlawii PG-8A cells. Raise of the amount of the minibodies that have increased
      resistance to biogenic and abiogenic stress factors and pathogenicity may lead to
      more successful persistence of mycoplasmas in their hosts. Increased production
      of the extracellular membrane vesicles containing virulence factors by
      Acholeplasma laidlawii cells during stress may be an additional burden for the
      infected organism. It has been recently revealed that the vesicles of A.
      laidlawii contain appreciable quantities of small heat shock protein IbpA
      (Hsp20). In this paper, using immune-electron microscopy, have shown that at
      elevated temperature IbpA is associated with A. laidlawii minibodies. Perhaps,
      IbpA contributes to increased resistance and pathogenicity of the minibodies,
      keeping their proteins and polypeptides, including protein virulence factors in
      the folding-competent state.

PMID- 25872371
TI  - [Tissue engineering in urology, new approaches for urinary bladder
      reconstruction].
AB  - Tissue engineering as applied to urologic pathology is covered extremely poor in
      the literature despite recently gaining popularity of regenerative medicine. The
      review reflects the current problems associated with reconstructive surgery of
      the urinary bladder, experience of the researchers from the United States in
      implementing cellular technologies for bladder replacement, the problems and
      prospects of this direction in case of such a severe pathology, as fibrous
      transformated bladder.

PMID- 25872372
TI  - [CRISPR/Cas system for genome editing in pluripotent stem cells].
AB  - Genome editing systems based on site-specific nucleases became very popular for
      genome editing in modern bioengineering. Human pluripotent stem cells provide a
      unique platform for genes function study, disease modeling, and drugs testing.
      Consequently, technology for fast, accurate and well controlled genome
      manipulation is required. CRISPR/Cas (clustered regularly interspaced short
      palindromic repeat/CRISPR-associated) system could be employed for these
      purposes. This system is based on site-specific programmable nuclease Cas9.
      Numerous advantages of the CRISPR/Cas system and its successful application to
      human stem cells provide wide opportunities for genome therapy and regeneration
      medicine. In this publication, we describe and compare the main genome editing
      systems based on site-specific programmable nucleases and discuss opportunities
      and perspectives of the CRISPR/Cas system for application to pluripotent stem
      cells.

PMID- 25872373
TI  - [Heterogeneity and possible structure of mesenchymal stromal cell population].
AB  - Mesenchymal stromal cells (MSC) represent a heterogeneous population of cells
      that differ in morphology, phenotype, ability to grow and differentiate, and
      other properties. Differences between MSC are related in part to the influence of
      their microenvironment. However, the heterogeneity of these cells also is due to
      their parent-progeny relationship. Hierarchical organization of the MSC
      population that comprises different categories of oligopotent and multipotent
      cells, is complicated and poorly understood. This review includes data on
      morphological, phenotypic and functional heterogeneity of MSC and its possible
      connection with the population structure.

PMID- 25872374
TI  - [Distribution in early mouse embryos of foreign mtDNA transmitted along the
      paternal lineage].
AB  - Transmission of foreign mtDNA along the paternal lineage founded by male mice
      (F0), and distribution of that mtDNA in their progeny at early stages of prenatal
      development were studied. Transmitochondrial males of F0 obtained after injection
      of human mitochondria into mouse zygotes has been shown to transmit foreign mtDNA
      to subsequent generations. Individual peculiarities among the males studied,
      concerning transmission of foreign mtDNA to the progeny, are likely to exist.
      Besides, the distribution of human mtDNA among blastomeres of transmitochondrial
      embryos under study differed from that observed in previous investogation of its
      inheritance along the maternal lineage.

PMID- 25872375
TI  - [Cohesion inside eu- and heterochromatin in human cells].
AB  - It is considered that sister chromatids are held together immediately after
      replication by special protein complex--cohesin that consists of Smc1--Smc3 core
      dimer and two additional subunits, Scc1 and Scc3. This process is called
      cohesion. We have characterized binding of cohesin complex to early- and late
      replicated chromatin at different stages of the cell cycle in human cells HeLa
      and HT1080 using superresolution microscopy (based on Structural ilumination
      microscopy--SIM) and immunoelectron microscopy. It has been shown that cohesins
      do not play important role in cohesion of heterochromatic domains, but they
      provide cohesion and organization of subdomains in euchromatic regions.

PMID- 25872376
TI  - [Expression of mRNA transcription factors RORC2 and FoxP3 in lymphocytes in
      patients with pulmonary tuberculosis].
AB  - Homeostasis of subpopulations Th17- and Treg-lymphocytes plays an important role
      in a holistic and coordinated process of eradication of pathogens and preventing
      the spread of infection in the body. Study of molecular mechanisms controlling
      the balance of these cells in the formation of immune deviation in the
      pathogenesis of infection are particularly relevant. The article presents the
      results of a study of mRNA expression of transcription factors Th17- and Treg
      lymphocytes--RORC2 and FoxP3, respectively, as well as the presence of these
      cells in peripheral blood in infectious disease (based on an example of infection
      caused by Mycobacterium tuberculosis). It was established that during the
      infiltrative (regardless of drug susceptibility testing) and disseminated drug
      susceptible pulmonary tuberculosis accompanied by Th17-polarized differentiation
      of T-lymphocytes, as evidenced by the increased number of CD4+CD161+IL17A+ cells
      in the blood in association with increased mRNA expression of the transcription
      factor RORC2 in lymphocytes. In disseminated drug-resistant pulmonary
      tuberculosis T-lymphocyte differentiation is carried out mainly in the direction
      of immunosuppressive Treg-cells, as evidenced by the increase in their number in
      the blood in association with elevated levels of mRNA expression of the
      transcription factor FoxP3 in lymphocytes.

PMID- 25872377
TI  - [Light- and electron-microscopic study of pelobiont Pelomyxa secunda (Gruber,
      1884) comb. nov. (Archamoebae, Pelobiontida)].
AB  - Morphology of a pelobiont Pelomyxa secunda (Gruber, 1884) comb. nov. was
      investigated at light- and electron-microscopical levels. Locomotive forms are
      elongated or cigar-shaped. The size of active forms varies from 200 to 300 MUm.
      Larger individuals (up to 400 MUm) are not able to directed movement. Organism
      can produce short, usually finger-shaped hyaline pseudopodia at the frontal side
      or laterally. The cell coat is represented by amorphous glycocalix, up to 300 nm
      in thickness. A thin periphery cytoplasmic zone is deprived of any organelles,
      vacuoles, endocytobionts and other inclusions and separated from main cytoplasm
      by a layer of arranged microfilaments. P. secunda is multinucleate organism;
      nuclei are of granular type. The nucleolar material is represented by two forms
      of discrete structures differing in size and electron density. Two or three
      layers of short microtubules organized in the parallel arrangement are associated
      with outer side of the nuclear envelop. P. secunda possess two types of obligate
      prokaryotic endocytobionts lying in individual symbiontophoric vacuoles.
      Undulipodia, kinetosomes and root microtubular derivatives are not observed in P.
      secunda cells as well as any developed cytoplasmic microtubular cytoskeleton.

PMID- 25872378
TI  - [Reason to split the genus Aurelia. Mesoglein from two populations differ].
AB  - The medusa, Aurelia aurita (Scyphozoa, Cnidaria), is considered to be a
      cosmopolitan species with a worldwide distribution in most seas from the poles to
      the tropics. Cnidarian is thought to possess two tissue layers: endoderm
      (gastroderm) and ectoderm, which are separated by huge mesoglea in medusa. The
      basic morphology of medusa is similar in different populations. Previously we
      have determined a new protein "mesoglein" as one of the main components of
      mesoglea. Deduced amino acid sequence of mesoglein contains Zona Pellucida (ZP)
      domain. In this paper, we have comparied of mesoglein and its gene in medusa from
      three habitats (White Sea (WsA), Black Sea (BsA), Japonic Sea (JsA)). The set of
      the mesoglea protein bands after SDS-PAGE is similar in all samples.
      Nevertheless, JsA mesogleins' M(r) is 53-55 kDa, while WsA and BsA mesogleins
      have M(r) of 47 kDa. Antibodies raised against WsA mesoglein recognize only
      mesogleins with M(r) of 47 kDa, but not 53-55 kDa, both on immunoblot and
      immunocytochemistry. Mesogleal cells and elastic fibrils are stained intensively
      in the mesoglea both from WsA and BsA but not from JsA. The possibility of gene
      divergency was checked by PCR with primers specific for WsA mesoglein gene. PCR
      products of expected length obtained on polyA-cDNA template from mesogleal cells
      of WsA and BsA medusa but not on cDNA of JsA medusa. Our results evidence that
      there are two different species in genus Aurelia: Aurelia aurita inhabits White
      and Black Seas while Aurelia sp. inhabits Japonic Sea. This is consistent with
      findings of other recept molecular biological studies.

PMID- 25872379
TI  - [Valve-like structures in motor cells of the leaf of Distichlis spicata "Yesen
      4A" (Poaceae)].
AB  - The salt gland of the leaf of Distichlis directly contacts the cells of
      interfascicular aquiferous parenchyma (motor cells). The cytoplasmic strand of
      motor cells produce deep invaginations, which form with the participation of
      mitochondria. The constriction of the cytoplasmic strand at the site of the
      localization of mitochondria leads to the fusion of the tonoplast and plasmalemma
      with mitochondrial membranes and the formation of a thin one-layer plate, a
      valve. At this locus, vacuolar and apoplast spaces are separated only by a valve.
      The cytoplasm of motor cells is filled with electron dense granules, which are
      considered as contractile elements. It is assumed that the cytoplasmic strand is
      involved in the reduction of the volume, which results in the generation of
      pressure on the valve. This leads to the direct throw-in of water into the
      apoplast space adjacent to the salt gland.

PMID- 25872380
TI  - [Choroidal nevi: clinical features].
AB  - The prevalence of choroidal nevi (CN) ranges from 1% to 10%. It may be hard to
      differentiate a small melanoma from an atypical ("malignatized") CN, which
      occupies an intermediate position between typical nevi and actual melanomas and
      can be referred to as "progressive" or "suspicious". The risk of malignant
      transformation of a CN ranges from 0.78% to 7%, thus necessitating the need for a
      detailed description of its clinical features. OBJECTIVE: To study clinical
      features of choroidal nevi in conjunction with their growth patterns. MATERIAL
      AND METHODS: A total of 80 patients (84 eyes) with choroidal nevi were studied,
      including 23 men and 57 women aged 65.33+/-3.26 years on average. The follow-up
      period was 12-48 months. In 26 cases (30.95%) age-related macular degeneration
      (AMD) was also present. RESULTS: Choroidal nevus is generally more common in
      women (71.25%). The right eye was involved in 36 cases, the left--in 48.
      Bilateral CN was diagnosed in 5% of cases. The follow-up period was 12-48 months.
      The nevi were mostly located in the juxtapapillary (11.9%) and macular (29.76%)
      regions. In 10 eyes they spread to the parafovea and foveola. The shape was
      typically round (73.8%), in the rest of cases--oval (26.2%). The size at
      presentation varied from 1 mm to 9 mm (2.93 mm on average). Diagnostic features
      of a stationary nevus (does not require a follow-up) have been identified. Nevus
      enlargement and changes in the overlying retina are indicative of progression.
      CONCLUSION: On the basis of clinical presentation all choroidal nevi can be
      classified as either stationary or progressing. If progression is suspected, a
      close follow-up is required. Progressive destruction of the overlying retina and
      early signs of visual impairment are risk factors for melanoma development.

PMID- 25872381
TI  - [Corneal examination in patients with bullous keratopathy before and after
      endothelial keratoplasty].
AB  - OBJECTIVE: To evaluate corneal status in patients with bullous keratopathy before
      and after endothelial keratoplasty. MATERIAL AND METHODS: A total of 16 patients
      (18 eyes) with bullous keratopathy were examined before and after DSAEK. Confocal
      microscopy ("Nidek", Japan) was used for corneal status evaluation. RESULTS:
      Follow-up examinations were performed 3, 6, and 24 months after the surgery. In
      all patients minor corneal opacity persisted for the whole follow-up period but
      tended to decrease. It is shown that visual acuity is most dependent on light
      scattering in the anterior stroma. CONCLUSION: Anterior stromal haze is shown to
      have greater impact on visual acuity than opacities, folds, and birefringent
      deposits within the host-donor interface. Duration of bullous keratopathy,
      patient's age, and comorbidity are the factors that influence anterior and deep
      stromal haze development and changes over time.

PMID- 25872382
TI  - [Intralamellar bandage keratoplasty for the treatment of progressive keratoconus
      (draft report)].
AB  - The article discusses surgical options currently available for different stages
      of keratoconus. Indications and possible complications of each method are
      described in detail. So called intralamellar bandage keratoplasty, a new surgical
      procedure developed in the Research Institute of Eye Diseases and aimed at
      stabilizing the disease, is presented. Preliminary results suggest that the
      procedure is a promissing method for corneal thickness restitution and early
      stabilization of progressive keratoconus.

PMID- 25872383
TI  - [Comparative evaluation of the effectiveness of various treatment modalities for
      accommodation disorders and acquired progressive myopia].
AB  - OBJECTIVE: To evaluate the effectiveness of non-surgical treatment of
      accommodation disorders and progressive myopia in children. MATERIAL AND METHODS:
      A total of 190 patients (380 eyes) with myopia aged from 6 to 18 years (10.79+/
      0.18 years on average) were enrolled and divided into 9 groups depending on the
      treatment prescribed. RESULTS: Comparative evaluation of different hardware-based
      treatment modalities for progressive myopia allowed to work out their optimal
      combination: "Visotronic", "MACDEL 09", and magnetophoresis of Taufon 4%. Such
      courses, provided twice a year, were associated with optimization of
      accommodative response and 1.9-2.8 times reduction of the rate of myopia
      progression. On the contrary, pleoptic therapy showed a negative effect on
      accommodative tonus and the rate of progression of acquired myopia. CONCLUSIONS:
      Comparative evaluation of different hardware-based treatment modalities for
      progressive myopia and accommodation disorders allowed to work out their optimal
      combination: "Visotronic", "MACDEL 09" and magnetophoresis of Taufon 4%. This
      treatment, provided twice a year, allows to increase accommodative reserves and
      volume, improve objective accommodative response, and reduce accommodative
      hypertonus as well as the rate of myopia progression (1.9-2.8 times over a 1.5
      year period). Under pleoptic therapy (specialized software, near field speckles,
      color pulse therapy, Ambliokor device), both accommodative tonus and the rate of
      myopia progression increased (1.3-1.5 and 1.6 times correspondingly).

PMID- 25872384
TI  - [Effect of surgery on quality of life in patients with epiretinal membrane].
AB  - OBJECTIVE: To study the effect of surgical treatment on quality of life (QOL) in
      patients with epiretinal membrane (EM). MATERIAL AND METHODS: A total of 48
      patients who underwent surgical treatment for EM were examined. QOL was assessed
      with the VFQ-25 questionnaire before and after the surgery (at 1 week and 6
      months). RESULTS: Before the surgery the total QOL index was significantly
      decreased by an average of 25% as compared with the controls (p<0.001). In the
      late postoperative period there was a progressive increase in the total index of
      QOL up to the level of the control group (p>0.05). CONCLUSION: Vitrectomy surgery
      improves visual functions and quality of life in patients with epiretinal
      membrane.

PMID- 25872385
TI  - [Topical cyclosporine for the treatment of ocular surface changes in contact lens
      wearers].
AB  - OBJECTIVE: To assess opportunities for the use of cyclosporine emulsion 0.05% for
      the treatment of dry eye syndrome in long-term contact lens wearers. MATERIAL AND
      METHODS: A total of 25 long-term contact lens wearers (50 eyes) with signs of dry
      eye syndrome and corneal epitheliopathy of different degree, unresponsive to
      conventional artificial tears therapy, were observed. All of them were prescribed
      cyclosporine emulsion 0.05% twice daily at 12-hour intervals 10 min before
      inserting contact lenses or after removing. Biomicroscopy with fluorescein eye
      stain test, determination of the tear film break-up time (Norn's test), optical
      coherence tomography of tear meniscus (OCT-meniscometry), Jones test, impression
      cytology, and corneal confocal microscopy (Confoscan-4, "Nidek", Japan) were used
      to evaluate the treatment effect. RESULTS: The treatment resulted in better
      contact lens tolerance, significantly increased mean values of tear film break-up
      time (by 13.2% at 1 month, 62% at 3 months, and 37.3% at 6 months as compared
      with the baseline) and basal tear secretion (by 29%, 32%, and 82.4% at 1, 3, and
      6 months correspondingly). Confocal microscopy revealed restitution of corneal
      superficial epithelial structure and cell density. Goblet cells were present in
      impression cytology specimens. CONCLUSION: Topical use of cyclosporine emulsion
      0.05% has a positive effect on morphofunctional parameters of ocular surface and
      promotes basal tear secretion and precorneal tear film stability.

PMID- 25872386
TI  - [Nanostructured bioplastic material for traumatic corneal injuries].
AB  - OBJECTIVE: To substantiate the use of nanostructured bioplastic material for the
      treatment of traumatic eye injuries. MATERIAL AND METHODS: The study enrolled 96
      eyes of 48 rabbits and was carried out in 3 series of experiments, different in
      the type of induced corneal trauma: mechanical erosion, alkaline or acid burn.
      The animals were clinically monitored and sacrificed for morphological
      investigation at days 3, 7, 14, 30, and 90. RESULTS: The size of mechanical
      corneal erosions was repeatedly evaluated with fluorescein eye stain test. In the
      experimental group, Hyamatrix biomaterial was topically administered according to
      an original technique. In the controls, soft contact lenses were inserted and
      sutured. Complete closure of the epithelial defect with no impact on corneal
      properties was achieved in 3 days in the experimental group and in4 days in the
      control group. As for alkaline and acid corneal burns, experimental and control
      groups received Hyamatrix biomaterial and Solcoseryl eye gel correspondingly. In
      the experimental group of alkaline burn the defect closed by day 7, in the
      controls--by day 10-11. Acid-induced corneal edema also resolved by day 7 in the
      experimental group and by day 14 in the control group. CONCLUSION: 1. The results
      of this experimental and morphological study prove the hyaluronic acid-derived
      nanostructured bioplastic material effective in accelerating corneal re
      epithelialization after mechanical erosions as compared with the controls. 2.
      Topical application of the hyaluronic acid-derived nanostructured bioplastic
      material shortens the exudative phase of inflammation, promotes corneal defect
      closure with formation of a more subtle opacification, and stimulates corneal
      restoration after chemical burns.

PMID- 25872387
TI  - [Role of Chlamydia trachomatis intraocular infection in the development of
      proliferative vitreoretinopathy (experimental study)].
AB  - OBJECTIVE: To study the influence of C. trachomatis infection on proliferative
      vitreoretinopathy (PVR) stimulation and development in an experimental model.
      MATERIAL AND METHODS: Intravitreal C. trachomatis injection was performed in 17
      rabbits (right eyes) out of which 8 developed minimal chlamydial damage (1 was
      further subjected to histopathological examination with pathogen detection in
      ocular structures and other 7 were included in the study group). The control
      group consisted of 7 rabbits with no laboratory evidence of chlamydial infection.
      PVR was induced by 4 peripheral retinal punctures with a 19 G needle. Follow-up
      methods included ophthalmoscopy, ultrasonography, and PVR grading according to
      the Fastenberg classification. Histopathological examination, supplemented with
      pathogen detection by direct immunofluorescence in the study group, was performed
      at weeks 7 and 20. RESULTS: PVR rate and severity were higher in the study group
      as compared with the controls (5 out of 7 rabbits, grade 2-4 vs. 2 out of 7
      rabbits, grade 0-1, p<0.01). In the study group, histopathological examination
      performed before and after the induction of PVR revealed a pronounced lymphocyte
      and macrophage infiltration, characteristic of infectious inflammation.
      Similarly, extra- and intracellular chlamydial inclusions could be found in the
      retina and/or zones of proliferation throughout the whole study period.
      Inflammation signs (including those of proliferation) were reliably less
      significant in the controls. CONCLUSION: C. trachomatis infection of the
      posterior segment contributes to PVR development due to associated chronic
      inflammation.

PMID- 25872388
TI  - [Ocular toxicity of intracamerally injected antibacterial and antifungal drugs
      (experimental and morphological study)].
AB  - OBJECTIVE: To study anterior eye segment toxicity of variously diluted brand name
      and generic antibiotic and antifungal drugs, including domestically produced
      generics (Moxifloxacin, asketin cefuroxime, amikacin, gentamicin, Diflucan, and
      amphotericin B), experimentally injected into the anterior chamber. MATERIAL AND
      METHODS: A total of 13 Chinchilla rabbits were included in the experiment. Group
      1 (6 rabbits) received sterile intracameral injections of 0.2 ml antibiotics and
      antifungals in concentrations suitable for intravenous administration
      (Moxifloxacin 1.6 mg/ml, Diflucan 2 mg/ml, and the following generics: asketin
      cefuroxime 125 mg/ml, amikacin 50 mg/ml, gentamicin 40 mg/ml, amphotericin B 50
      mg/m). BSS was injected into the fellow eye for control. Group 2 (7 rabbits) also
      received sterile intracameral injections of 0.2 ml antibiotics and antifungals,
      which were the same as for group 1 but highly diluted (Moxifloxacin 150 MUg/ml
      and 500 MUg/ml, Diflucan 10 MUg/ml, asketin cefuroxime 1 mg/ml, gentamicin 200
      MUg/ml, amikacin 400 MUg/ml, amphotericin B 10 MUg/ml). RESULTS: There were no
      toxic effects in group 1 after BSS and Moxifloxacin 1.6 mg/ml injections into the
      anterior chamber. However, high concentrations of other antibiotic and antifungal
      drugs were associated with changes in the corneal endothelium of various severity
      (from cytoplasmic swelling of the endothelial cells to their complete
      desquamation), as well as fibrin exudation in the posterior chamber. In group 2
      neither of injected drugs caused toxic, allergic, or inflammatory reactions
      according to histopathological examination. CONCLUSION: The experiment proved
      safety of the intracameral route of administration for highly diluted medications
      from the list and also demonstrated the absence of toxic reaction after
      intracameral injection of Moxifloxacin 1.6 mg/ml.

PMID- 25872389
TI  - [Histopathological study of experimental intrapalpebral injection of hyaluronic
      acid gel].
AB  - Hyaluronic acid gel (HAG) fillers are successfully used in the treatment of many
      eyelid disorders. It is considered that the effect of HAG injection lasts for 6
      months on average. However, in our experience volume augmentation persists
      longer, suggesting that the presence of the filler in the eyelid may be
      associated with certain tissue reactions. The objective of the study was to
      investigate morphological features of HAG biodegradation. MATERIAL AND METHODS:
      Seven adult Chinchilla rabbits (14 eyes) received a single 0.1 ml HAG (Restylane,
      Q-Med AB, Sweden) subcutaneous upper eyelid injection followed by contouring of
      the skin for 1.5 mm on average. Tissue samples containing HAG were collected for
      histopathological examination with morphometric analysis on day 0, week 2, months
      1, 2, 4, 6, and 9. RESULTS: HAG persisted subcutaneously in the eyelid during the
      9 months of the study in the form of a sponge-like structure with compartments of
      varying shape and size. Its total volume diminished gradually, nevertheless at
      the end of the study the filler could still be found in some compartments, mainly
      peripheral. In the central area of the depot residual HAG was surrounded by
      optically transparent spaces. CONCLUSION: After being injected subcutaneously
      into the eyelids of experimental animals HAG formed a sponge-like structure
      causing a significant increase in eyelids volume. Gradual biodegradation of HAG
      was accompanied by neocollagenogenesis and 9 months later the process was still
      ongoing.

PMID- 25872390
TI  - [Options for prolonging the hypotensive effect of trabeculectomy].
AB  - OBJECTIVE: To assess potential of preoperative therapy with local steroid and non
      steroid anti-inflammatory drugs (SAIDs and NSAIDs) for prolonging the hypotensive
      effect of trabeculectomy. MATERIAL AND METHODS: A total of 80 patients with
      primary open-angle glaucoma planed for trabeculectomy were randomized into 4
      groups of 20 each: 3 groups that differed in the studied drug (nepafenac,
      dexamethasone, or their non-fixed combination) and a control group with no
      preoperative therapy. The patients instilled 1 drop of either drug b.i.d. for 2
      weeks before the surgery and were examined each day of the first week and then at
      weeks 1, 2, 4 and months 3, 6, and 12. The rate of postoperative surgical and
      medical interventions (needling, needling revision, hypotensive therapy) was used
      for outcome evaluation. RESULTS: Postoperative needling was required in 50% of
      the controls, 35% of the NSAIDs and 30% of the SAIDs patients as well as 20% the
      combination-therapy patients. Needling revision had to be performed in 10% of
      patients from the control group and 5% of patients from the NSAIDs group.
      Patients from the steroid and combination-therapy groups had no need in needling
      procedure. Further hypotensive therapy was required in 50% of the control group,
      35% of the NSAIDs group, 25% of the SAIDs group and 20% of the combination
      therapy group. During the first postoperative year complete success of the
      treatment was achieved in 50% of the controls, 65% of the NSAIDs patients, 75% of
      the SAIDs patients, and 80% of those under combination therapy. Qualified success
      during the same period was achieved in 100% of cases. CONCLUSION: Preoperative
      local anti-inflammatory therapy helped to increase the one-year complete success
      rate after trabeculectomy as compared with the controls. The most significant
      hypotensive effect was noted in the combination-therapy group (80%), less
      significant--in the steroid and non-steroid monotherapy groups (75% and 65%
      correspondingly). A negative correlation was noted between the use of nepafenac
      and dexamethasone and other measures aimed at increasing the hypotensive effect
      of glaucoma surgery.

PMID- 25872391
TI  - [A case of bilateral cystoid macular edema (Irvine-Gass) after bilateral
      multifocal intraocular lens implantation].
AB  - OBJECTIVE: To evaluate clinical outcomes of cystoid macular edema (CME) developed
      after phacoemulsification with multifocal intraocular lens (IOL) implantation.
      MATERIAL AND METHODS: The article reports a favorable outcome of bilateral CME in
      a 66-year-old after bilateral phacoemulsification with Rayner M-flex Multifocal
      IOLs implantation. Optical coherent tomography (OCT) and multifocal
      electroretinography (mfERG) were used for follow-up. RESULTS: In the first eye
      CME developed 3 weeks after the surgery and required 1.5 years of treatment. In
      the fellow eye CME manifested 2 weeks after the surgery and resolved in six
      months under the treatment. The follow-up period was 5 and 2 years
      correspondingly. CONCLUSION: It is shown that retinal OCT is useful for
      distinguishing clinical forms of CME and is able to confirm positive effects of
      the treatment, whereas mfERG provides the opportunity to assess subtle mechanisms
      of retinal function recovery, which may take several years.

PMID- 25872392
TI  - [Prognostic factors for uveal melanoma].
AB  - Uveal melanoma is a malignant intraocular tumor associated with poor vital
      prognosis, process generalization, and death from metastatic disease. A number of
      factors are considered undesirable in the presence of a tumor. This paper
      provides a review of the literature on major prognostic factors for uveal
      melanoma development and their contribution to vital prognosis.

PMID- 25872394
TI  - [Opportunities for confocal and laser biomicroscopy of corneal nerves in diabetic
      polyneuropathy].
AB  - The review concerns corneal nerves involvement in diabetes mellitus (DM), a
      pressing issue for ophthalmology and endocrinology. The history of research in
      this field along with anatomical, physiological, and biochemical features of
      corneal nerves is provided. Corneal nerves anatomy is described in accordance
      with Soviet scientific school and contemporary foreign sources. The most part of
      the paper is devoted to technical description of a confocal microscope and
      Heidelberg Retina Tomograph with corneal module as well as the feasibility of
      corneal nerves visualization. Diabetic neuropathy, a threatening complication of
      DM that can result in lower limb amputations, is discussed. A number of authors
      suggest confocal biomicroscopy for early diagnosis of polyneuropathy, yet few
      relevant publications can be found. If effective, confocal biomicroscopy can be
      considered as a possible screening tool able to detect early signs of diabetes
      complications and thus to ensure the treatment initiated in a timely manner. The
      latter is crucial to prevent DM progression to its terminal stage--diabetic
      polyneuropathy, which is dangerous of lower limb amputations.

PMID- 25872393
TI  - [Ocular surface system integrity].
AB  - The interplay of different structures belonging to either the anterior segment of
      the eye or its accessory visual apparatus, which all share common embryological,
      anatomical, functional, and physiological features, is discussed. Explanation of
      such terms, as ocular surface, lacrimal functional unit, and ocular surface
      system, is provided.

PMID- 25872395
TI  - [Competence factors of retinal pigment epithelium cells for reprogramming in the
      neuronal direction during retinal regeneration in newts].
AB  - Retinal pigment epithelium (RPE) cells that have the unique ability to reprogram
      retinal cells @in vivo@ were analyzed in the adult newt. Our own data and that
      available in the literature on the peculiarities of the biology of these cells
      (from morphology to molecular profile, which can be associated with the
      capability of phenotype change) were summarized: It was established that the
      molecular traits of specialized and poorly differentiated cells are combined in
      RPE of the adult newt. It was registered that persistent (at a low level)
      proliferation and rapid change of specific cytoskeleton proteins can contribute
      to the success of RPE cell reprogramming in the neuronal direction. Each of the
      considered factors of competence for reprogramming can be found for animal RPE,
      whose cells are not able @in vivo@ to change the phenotype to a neuronal one;
      however, their totality (supported by the epigenetic state permissive for
      conversion) is probably an internal property of only newt RPE.

PMID- 25872396
TI  - [Perinatal stress in brain programming and pathogenesis of psychoneurological
      disorders].
AB  - We analyzed data from our studies and other author's works concerning the
      influence of stress stimuli on the development of neuroendocrine and immune
      systems. The results of our analysis suggest that "immunological stress" induced
      by viral or bacterial infection, an unhealthy diet, and the mother's behavior
      during pregnancy and lactation are significant risk factors for the developing
      offspring. The brain is the key target for these factors. The continuous effect
      of stress stimuli during critical periods of brain development induces
      hyperactivity and increased response of hypothalamic-pituitary-adrenal system.
      This can increase the risk of the development of psychoneurological, metabolic,
      immunological, and behavioral disorders and the suppression of reproduction in
      the offspring. The plasticity of physiological systems helps the developing
      organism to adapt to the changing environment.

PMID- 25872397
TI  - [Peculiarities of Proteus mirabilis extracellular metalloproteinase
      biosynthesis].
AB  - Biosynthesis of metalloproteinase by the Proteus mirabilis 5127-1 strain on
      different media and the influence of glucose and urea on biosynthesis were
      studied. It was found that the P. mirabilis 5127-1 bacteria secretes
      metalloproteinase in the medium in two isoforms (52 and 50 kDa). It was
      established that proteinase synthesis is completely suppressed during the growth
      of bacteria on synthetic media, as well as in the presence of LB glucose in the
      medium. It was demonstrated that addition of urea in the medium results in an
      increase of the culture productivity in the proteinase synthesis. Maximal culture
      productivity in the proteinase synthesis was found in the medium with natural
      urine. During the growth of bacteria on artificial urine, proteinase appeared in
      the medium only after 12 hours of growth as a single isoform.

PMID- 25872398
TI  - [The effect of salicylic and jasmonic acids on the activity and range of
      protective proteins during the infection of wheat by the septoriosis pathogen].
AB  - The influence of salicylic (SA) and jasmonic (JA) acids as signaling systems
      mediators on the generation of H2O2 and expression of genes encoding protective
      proteins was studied in the leaves of wheat Triticum aestivum L. upon infection
      with the pathogen of septoriosis Septoria nodorum Berk. It was found that
      presowing treatment of seeds with SA and JA decreased the development of the
      fungus on the leaves of wheat and had a stimulating effect on the production of
      H2O2 in the area of infection. An increased expression of genes encoding oxalate
      oxidase AJ556991.1 and anionic peroxidase TC 151917 was shown in infected tissues
      with the method of polymerase chain reaction.

PMID- 25872399
TI  - [Composition and distribution of the mitochondrial lineages of gray whales
      (Eschirichtius robustus) in the far eastern seas of Russia].
AB  - The frequency of occurrence of the mitotypes (control region, cytochrome b gene,
      and DN2 gene) has been studied for groups of gray whales feeding and growing
      along Chukotka Peninsula, Koryak Coast, eastern Kamchatka, and Sakhalin Island.
      The number of the mitotypes decreased dramatically from the northern waters
      southwards; however, the dominant mitotypes remained the same. Both mitochondrial
      lineages known for this species might be found for the whales gathering in the
      reproductive area along the Californian Coast in accordance with the comparison
      of the published and original data on the haplotypes of the control region.
      However, it has also been argued that similar sequences of the control region
      might be found in different mitochondrial genomes, and the analysis of only this
      site of mtDNA might lead to incorrect conclusions.

PMID- 25872400
TI  - [Downstream migration, behavior, and distribution of fish fry in the lower
      reaches of the Ozernaya River (southwestern Kamchatka)].
AB  - Fry of five species of salmonids are found in the lower reaches of the Ozernaya
      River. The most abundant are chum salmon and pink salmon which compose the bulk
      of fry which migrate downstream from the river to the sea. The dates and duration
      of migration of particular species differed according to the specific traits of
      their biology. Pink salmon is characterized by a simple migration strategy: it
      migrated downstream in a short time after emergence from theground. Chum salmon
      has two strategies of downstream migration: some fry start migration soon after
      emergence, and others remained in the river for several weeks. Downstream
      migration of pink salmon occurred mainly at night in contrast to that of chum
      salmon, over 24 h, the part of daytime increased with growth, of the fish.
      Migration of pink salmon was passive. Passive migration of chum salmon changed
      into active-passive with growth of the fish. The ratio of fish in the inshore
      zone and in the current was different in the course of 24 h. The number of fish
      in the inshore zone decreased in the period of intensive downstream migration.

PMID- 25872401
TI  - [Cranial features and feeding types of subspecies forms of Moschus moschiferus L.
      (Moschidae, Cetartiodactyla)].
AB  - The relationship between the cranial features and feeding types in the musk deer
      has been studied. According to the results of dispersion and cluster analyses,
      the six modern subspecies were divided into four trophic (mixed-feeders)
      subcategories--by the ratio of grass and leaves with a significant fraction of
      lichens (from 25 to 75%) in their diet. It was established that some
      morphological features of the skulls of subspecies forms correlate with their
      feeding specialization and habitat and can thus be useful in the reconstruction
      of adaptations of extinct Moschidae taxa.

PMID- 25872402
TI  - [The effect of magnetic fields on the activity of proteinases and glycosidases in
      the intestine of the crucian carp Carassius carassius].
AB  - It has been demonstrated by the example of the crucian carp (Carassius carassius)
      that a 1-hour stay of fish in a combined magnetic field with resonance parameters
      for calcium ions decreases the proteolytic and amylolytic activities of their
      intestinal enzymes. It has been found that a 1-hour exposure to a combined
      magnetic field with resonance parameters for potassium ions has almost no effect
      on the activity of proteinases, but it decreases the amylolytic activity. It has
      been noted that the activity of proteases and glycosidases is lower under
      hypomagnetic conditions. Upon the inversion of the vertical component of the
      geomagnetic field, the proteolytic activity of the intestinal mucosa in C.
      carassius decreases, while the amylolytic activity becomes higher compared to the
      control. Possible effects of magnetic fields on the activity of digestive
      hydrolases in fish are discussed.

PMID- 25872403
TI  - [Inhibitors of neuronal and inducible NO-syntases enhance the effect of short
      term adaptation to hypoxia in rats of Krushinsky-Molodkina strain].
AB  - We found that selective inhibitors of neuronal and inducible NOS (7-nitroindazole
      and aminoguanidine) significantly enhance the protective effect of short-term
      adaptation to hypoxia on the development of stress lesions in rats Krushinsky
      Molodkina.

PMID- 25872404
TI  - [In vitro lipid-lowering and fibrinolytic effects of regulatory leucine
      containing glyprolines in human blood].
AB  - The lipid-lowering, fibrinolytic, and anticoagulant effects of leucine-containing
      glyprolines, Pro-Gly-Pro-Leu and Leu-Pro-Gly-Pro, were studied in vitro in the
      blood of patients with disorders of lipid metabolism. The lipid-lowering impact
      of glyprolines and their ability to reduce the polymerization and to increase the
      depolymerization of fibrin in human blood were found. Possible mechanisms of
      lipolytic action of peptides by means of modulation of the lipid-dependent
      phospholipase A2 were proposed.

PMID- 25872405
TI  - [Diurnal dynamics of thyroid and sex steroid hormones in the blood of yearlings
      of the resident form of Black Sea trout Salmo trutta labrax].
AB  - The diurnal dynamics of the content of thyroid and sex steroid hormones is
      investigated in the blood of the resident form of Black Sea trout in summer. The
      maximums and minimums of concentration of the investigated hormones do not
      coincide over 24 h, except for the decrease in the level of T3 and testosterone
      before dawn. The dynamics of the investigated hormones is controlled to a high
      extent by the sex of fish in the morning and in the daytime.

PMID- 25872406
TI  - [All-Russia Conference with international participation on embryonic development,
      morphogenesis, and evolution dedicated to the 135th anniversary of P. P. Ivanov].

PMID- 25872407
TI  - Cost and Quality: The Duality of Efficiency.

PMID- 25872408
TI  - Is an Increase in Thyroid Nodule Volume a Risk Factor for Malignancy?
AB  - BACKGROUND: Most benign thyroid nodules found on fine-needle aspiration cytology
      (FNAC) can be followed with periodic ultrasonography. During follow-up, when
      nodules grow, re-aspiration or surgical resection for a histologic diagnosis is
      recommended. However, there is little evidence regarding the malignancy risk
      associated with nodule growth. METHOD: We retrospectively reviewed the records of
      542 patients with FNAC-diagnosed adenomatous nodules (ANs) who underwent surgery
      in 2011-2012 at Kuma Hospital. Among them, 196 patients had surgical resection
      because of nodule volume growth (median, 1.94 times; range, 1.21-27.60) during
      the observation period (mean, 45.9 months). Excluding nodule growth, the
      remaining 346 patients underwent surgery for various reasons including the large
      size of nodules or the appearance of undefined ultrasound features suspicious for
      malignancy during follow-up. For comparison, we reviewed 409 patients with FNAC
      diagnosed follicular neoplasms (FNs) operated on in 2011-2013. Most (n=327)
      underwent surgery shortly after the FNAC diagnosis, while 82 patients were
      observed for a period of time and had a late operation due to nodule volume
      growth (median, 2.70 times; range, 1.27-15.82). RESULTS: The histologic diagnoses
      of the 196 growing FNAC-diagnosed ANs were 158 ANs, 32 follicular adenomas (FAs),
      4 follicular tumors of uncertain malignant potential (FT-UMP; 2%), and 2
      malignancies (1%). The 346 patients who underwent surgery for reasons other than
      nodular growth had 16 FT-UMP (4.6%) and 16 malignancies (4.6%). This suggests
      that nodule growth itself is not a risk factor for malignancy. On the other hand,
      there were 23 FT-UMP (28%) and 15 malignancies (18.3%) in the 82 growing FNAC
      diagnosed FNs, while 44 FT-UMP (13.5%) and 54 malignancies (16.5%) in the 327
      FNAC-diagnosed FN patients who underwent immediate surgery. The malignant
      potential was significantly higher in the growing-FN group than the immediate
      surgery FN group (p<0.05). No significant difference was found in the volume
      change between the benign and the FT-UMP plus malignant group in the growing FNs,
      suggesting that a growth rate does not correlate with malignant potential.
      CONCLUSION: This is the first demonstration that the malignancy risk is low in
      FNAC-diagnosed ANs, even if the nodules grow significantly, whereas FNs have a
      higher risk when they grow.

PMID- 25872409
TI  - Single cusp replacement in patients with ventricular septal defect and aortic
      insufficiency.
AB  - OBJECTIVE: The aim of this study was to analyze the mid- and long-term outcome of
      single cusp replacement in patients with ventricular septal defect and aortic
      insufficiency. METHODS: From September 2005 through March 2014, 172 patients
      underwent single cusp replacement and ventricular septal defect (VSD) closure.
      The median age was 19.5 years (range, 9 months to 67 years). Additional
      techniques were used to repair associated anomalies including sinus of Valsalva
      aneurysm, patent ductus arteriosus, patent foramen ovale, subaortic membrane, and
      intramural coronary artery. RESULTS: One patient with large left ventricle
      (preoperative end-diastolic diameter: 9.8 cm) died after the procedure from
      incurable heart failure. Four patients required a second pump run for residual
      aortic insufficiency (AI) (two patients, 1.16%) and residual VSD (two patients,
      1.16%). Four patients required re-exploration for postoperative bleeding or
      cardiac tamponade. Mean follow-up was 53.27 +/- 25.37 months (median, 56.5
      months; range, 3 to 104 months). Redo aortic valve surgery was performed in three
      patients. Three patients had moderate-severe AI during the following period
      without reoperation. There was no post-operative endocarditis. CONCLUSION: Single
      cusp replacement can be safely used in patients with VSD-AI.

PMID- 25872410
TI  - Induction of MUC5AC mucin expression by histamine through the activation of its
      core promoter region.
AB  - CONCLUSION: This study provides evidence that histamine induced MUC5AC mRNA
      expression through the activation of the core region of its promoter. It may also
      help in approaching new therapeutic strategies in airway mucins hypersecretory
      diseases. OBJECTIVE: Mucin hypersecretion characterizes several respiratory
      diseases. Production of MUC5AC, a major gel forming mucin secreted by airway
      epithelia, can be induced by various inflammatory mediators. Histamine is
      associated with MUC5AC up-regulation during the early phase of allergic
      respiratory diseases. The goal of the present study was to identify whether
      histamine may induce MUC5AC gene expression both at mRNA and protein levels and
      to elucidate its mechanism. METHODS: Guinea pigs were sensitized and challenged
      with dermatophagoides farinae (Der f) extract. Human lung mucoepidermoid
      carcinoma cell line (NCI-H292) was used. The regulatory mechanism of MUC5AC by
      histamine and H1R was investigated using RT-PCR, immunofluorescence, and MUC5AC
      promoter-driven luciferase reporter assay. RESULTS: The MUC5AC expression levels
      were increased by histamine treatment in either nasal tissues of Der f challenged
      guinea pigs or NCI-H292 cells, whereas the MUC5AC protein over-production induced
      by histamine administration was significantly inhibited by H1R antagonist
      chlorpheniramine. It was found that histamine enhanced the activation of the
      proximal core region of the MUC5AC promoter, which was significantly blocked by
      chlorpheniramine, as indicated by luciferase reporter assays.

PMID- 25872411
TI  - Postoperative morbidity survey, mortality and length of stay following emergency
      laparotomy.
AB  - Thirty-day mortality following emergency laparotomy is high, and greater amongst
      elderly patients. Studies systematically describing peri-operative complications
      are sparse, and heterogeneous. We used the postoperative morbidity survey to
      describe the type and frequency of complications, and their relationship with
      outcomes for 144 patients: 114 < 80 years old, and 30 >= 80 years old. Cumulative
      postoperative morbidity survey scores and patterns of morbidity were similar (p =
      0.454); however, 28-day mortality was higher in the elderly (10/30 (33.3%) vs.
      11/114 (9.6%), p = 0.008), and hospital stay was longer (median (IQR [range]) 17
      (13-35 [6-62]) days vs. 11 (7-21 [2-159]) days, p = 0.006). Regression analysis
      indicated that cardiovascular, haematological, renal and wound complications were
      associated with longer hospital stay, and that cardiovascular complications
      predicted mortality. The postoperative morbidity survey system enabled structured
      mapping of the number and type of complications, and their relationship with
      outcome, following emergency laparotomy. These results indicate that rather than
      a greater propensity to complications following surgery, it was the failure to
      tolerate these that increased mortality in the elderly.

PMID- 25872413
TI  - Severe and fatal adverse events risk associated with rituximab addition to B-cell
      non-Hodgkin's lymphoma (B-NHL) chemotherapy: a meta-analysis.
AB  - PURPOSE: Rituximab is a monoclonal antibody targetting the CD20 antigen with the
      ability to increase overall remission (OR) in B-cell non-Hodgkin's lymphoma (B
      NHL). A systematic review and meta-analysis were conducted to determine the risk
      of the most clinically relevant severe and fatal adverse events (AEs) associated
      with the use of rituximab in the treatment of B-NHL. PATIENTS AND METHODS: We
      included phase III clinical trials that used chemotherapy in combination with
      rituximab or chemotherapy alone as for B-NHL. Statistical analyses were conducted
      to calculate summary risk ratio (RR) of the relevant severe and fatal AEs related
      with rituximab. RESULTS: Eight randomised controlled clinical trials were
      included in this meta-analysis. Summary RR obtained showed no statistically
      significant rituximab-associated increased risk in 13 severe adverse events
      (SAEs) (infection, fever, anaemia, thrombocytopaenia, granulocytopenia, liver
      toxicity, cardiac toxicity, neurologic toxicity, lung toxicity, mucositis,
      nausea/vomiting, diarrhoea, alopecia) except leukocytopenia (36.4% versus 31%; RR
      = 1.13; 95%CI, 1.01-1.27; P = 0.03). The incidences of fatal AEs showed
      noteworthy difference between rituximab group and control group (RR = 1.45; 95%
      CI, 1.04-2.02; P = 0.03). CONCLUSION: This meta-analysis indicates that there was
      no proof of statistically higher incidence of most SAEs in rituximab containing
      group compared with chemotherapy alone. However, fatal infections were more
      frequently observed in patients who received rituximab. Considering the low
      incidence infection-induced death during the treatment period, the effects of
      rituximab on infections need further investigation.

PMID- 25872412
TI  - Diverse supramolecular structures formed by self-assembling proteins of the
      Bacillus subtilis spore coat.
AB  - Bacterial spores (endospores), such as those of the pathogens Clostridium
      difficile and Bacillus anthracis, are uniquely stable cell forms, highly
      resistant to harsh environmental insults. Bacillus subtilis is the best studied
      spore-former and we have used it to address the question of how the spore coat is
      assembled from multiple components to form a robust, protective superstructure.
      B. subtilis coat proteins (CotY, CotE, CotV and CotW) expressed in Escherichia
      coli can arrange intracellularly into highly stable macro-structures through
      processes of self-assembly. Using electron microscopy, we demonstrate the
      capacity of these proteins to generate ordered one-dimensional fibres, two
      dimensional sheets and three-dimensional stacks. In one case (CotY), the high
      degree of order favours strong, cooperative intracellular disulfide cross
      linking. Assemblies of this kind could form exquisitely adapted building blocks
      for higher-order assembly across all spore-formers. These physically robust
      arrayed units could also have novel applications in nano-biotechnology processes.

PMID- 25872414
TI  - Gastrocele: a rare cause of pain abdomen after colonic bypass for corrosive
      stricture esophagus.

PMID- 25872415
TI  - Long-term cost-effectiveness of Oncotype DX(r) versus current clinical practice
      from a Dutch cost perspective.
AB  - INTRODUCTION: This study analyzes the incremental cost-effectiveness of Oncotype
      DX((r)) testing to support adjuvant chemotherapy recommendations, versus current
      clinical practice, for patients with estrogen receptor-positive (ER(+)), node
      negative or micrometastatic (pN1mic) early-stage breast cancer in The
      Netherlands. METHODS: Markov model projecting distant recurrence, survival,
      quality-adjusted life years (QALYs) and healthcare costs over a 30-year time
      horizon. RESULTS: Oncotype DX was projected to increase QALYs by 0.11 (0.07-0.58)
      and costs with ?1236 (range: -?142-?1236) resulting in an incremental cost
      effectiveness ratio of ?11,236/QALY under the most conservative scenario.
      CONCLUSION: Reallocation of adjuvant chemotherapy based on Oncotype DX testing is
      most likely a cost-effective use of scarce resources, improving long-term
      survival and QALYs at marginal or lower costs.

PMID- 25872416
TI  - CD24 Ala57Val polymorphism is associated with spontaneous viral clearance in the
      HCV-infected Chinese population.
AB  - BACKGROUND & AIMS: Host immune response to hepatitis C virus (HCV) is a vital
      factor involved in both viral clearance and liver disease pathogenesis. CD24
      plays an important role in inflammation and immune response and CD24
      polymorphisms are associated with risk and progression of chronic hepatitis B
      virus infection. Our study evaluated whether CD24 polymorphisms affect HCV
      clearance. METHODS: We genotyped 544 chronic hepatitis C (CHC) patients, 78
      spontaneous hepatitis C clearance (SHC) patients and 215 healthy controls for
      CD24 gene variants at positions -P534, P170, P1527 and IFNL3 rs12979860 by
      pyrosequencing. In CHC patients, 362 individuals were treated with a recombinant
      IFN-alpha2b/ribavirin combination for 48 weeks and were followed up for an
      additional 24 weeks. Lymphocyte CD24 expression was analysed by flow cytometry.
      RESULTS: We show that P170 CT and CT/TT genotypes were over-represented in the
      SHC group compared to CHC patients (62.8% vs. 47.2% and 75.6% vs. 60.3%, for
      respective polymorphisms). In multivariate logistic analysis, P170 (CD24
      Ala57Val) polymorphism was an independent predictor of SHC (adjusted OR = 2.11,
      95%CI = 1.19-3.73, P = 0.010 for CT genotype; OR = 2.01, 95%CI = 1.15-3.49, P =
      0.014 for CT/TT genotype). No significant associations were found between the
      CD24 polymorphisms and treatment-induced viral clearance in log-rank analysis and
      Cox regression analysis. Patients with the CT/TT genotype had greater T-cell CD24
      expression than patients with the CC genotype. CONCLUSIONS: Our findings suggest
      that CD24 Ala57Val polymorphism and associated variations in CD24 expression may
      be an important predictor for SHC, but have no effect on antiviral drug treatment
      response in Chinese CHC patients.

PMID- 25872417
TI  - Cytomegalovirus-related childhood mortality in Australia 1999-2011.
AB  - AIM: Cytomegalovirus (CMV) is an important cause of congenital infection, which
      can result in neonatal deaths or contribute to deaths in later childhood. Post
      natally acquired CMV is a less common cause of disease and mortality, and only in
      preterm infants or immunocompromised children. Here we sought to describe CMV as
      a direct or secondary contributor to childhood mortality in Australia. METHOD: We
      searched national mortality data sets between1999 and 2011 for cases <15 years
      with CMV recorded as an underlying or contributing cause of death. RESULTS:
      Eighty-three CMV-associated deaths in children <15 years were identified (0.2
      cases per 100 000 <15 years; 95% confidence interval 0.16-0.24). Childhood deaths
      associated with CMV were evenly distributed between males and females, and the
      majority (n = 57; 68%) occurred in children less than 12 months of age, with 22
      cases <1 month of age. Over the 13-year study period, the mortality rate remained
      stable and CMV resulted in an estimated age-adjusted 5925 years of potential life
      lost. CONCLUSIONS: CMV makes a small but important contribution to childhood
      mortality in Australia. Most CMV-related deaths occurred in infants <12 months of
      age. These infant deaths may be an indirect marker of the burden of severe
      intrauterine CMV disease given the natural history of this infection.

PMID- 25872418
TI  - Enhancing toxic metal removal from acidified sludge with nitrite addition.
AB  - The production of sludge (biosolids) during wastewater treatment is a major issue
      for water utilities. A main issue limiting its beneficial reuse on agricultural
      lands is the presence of toxic metals. The currently used metal reduction
      technologies achieve insufficient removal of metals that are bound to the organic
      fraction of the sludge. In this study, we propose and demonstrate a novel method
      that involves the addition of nitrite during sludge acidification to enhance
      metal removal. Using waste activated sludge collected from three full-scale
      wastewater treatment plants, we found that acidification to pH 2.0 achieved good
      Zn solubilization of around 70%, but only 3-7% of Cu was being dissolved. Nitrite
      addition to the acidified sludge at a concentration of 20 mg NO2(-)-N/L (equals
      to 19.2 mg HNO2-N/L), substantially enhanced Cu removal to 45-64%, while Zn
      removal was also increased to over 81%. Metal distribution analysis using
      sequential chemical extraction revealed that the improvement of Cu and Zn removal
      was mainly due to the release of the organically bound metal fraction. We
      hypothesize that free nitrous acid (HNO2, FNA) may assist in the (partial)
      disruption of extracellular polymeric substances (EPS) and the subsequent release
      and solubilization of fixed metals. 

PMID- 25872419
TI  - A novel platform based on immobilized histidine tagged olfactory receptors, for
      the amperometric detection of an odorant molecule characteristic of boar taint.
AB  - We report a dose-dependent detection of androstenone in solution, as one of the
      boar taint compounds, based on related OR7D4 olfactory receptors immobilized on a
      gold electrode through their 6-His tag and NTA-copper complex, as visualized
      through fluorescence microscopy. Square wave voltammetry (SWV) is for the first
      time, the method used to monitor the olfactory receptor/odorant recognition
      process. The relative variation of the Cu(I)-Cu(II) current peak increases
      linearly versus log (concentration of androstenone) from 10(-14)M to 10(-4)M, in
      buffer solution. Negative tests were performed, using an unrelated odorant,
      helional, itself a ligand of OR 1740. Cross-selectivity was also tested after
      immobilization of OR 1740.

PMID- 25872420
TI  - A molecular imprinted SPR biosensor for sensitive determination of citrinin in
      red yeast rice.
AB  - A novel and sensitive molecular imprinted surface plasmon resonance (SPR)
      biosensor was developed for selective determination of citrinin (CIT) in red
      yeast rice. Firstly, the gold surface of SPR chip was modified with allyl
      mercaptane. Then, CIT-imprinted poly(2-hydroxyethyl methacrylate
      methacryloylamidoglutamic acid) (p(HEMA-MAGA)) film was generated on the gold
      surface modified with allyl mercaptane. The unmodified and imprinted surfaces
      were characterized by Fourier transform infrared (FTIR) spectroscopy, atomic
      force microscopy (AFM) and contact angle measurements. The linearity range and
      the detection limit were obtained as 0.005-1.0 ng/mL and 0.0017 ng/mL,
      respectively. The SPR biosensor was applied to determination of CIT in red yeast
      rice sample.

PMID- 25872421
TI  - NMR approach for monitoring post-mortem changes in Atlantic salmon fillets stored
      at 0 and 4 degrees C.
AB  - High resolution NMR technique has been used to monitor post-mortem changes in
      salmon (Salmo salar) fillets upon storage at 4 and 0 degrees C. Thirty-one
      different fish metabolites influencing freshness and taste properties have been
      unequivocally assigned by NMR using either available standard compounds or ad hoc
      acquired 2D (1)H-(1)H TOCSY and (1)H-(13)S HSQC spectra. The monitored fish
      metabolites include amino acids, dipeptides, sugars, vitamins, biogenic amines,
      as well as different products of the ATP degradation. The detection and
      monitoring of biogenic amines by NMR, upon fish storage, is information of
      interest for consumers, since some of these compounds are toxic. The data from
      this study shows that NMR spectroscopy also provides the amount of all
      metabolites necessary for the calculation of the K-index used to express fish
      freshness. A good correlation was found between the K-index increase and the
      formation of the undesired biogenic amines. The metabolite concentrations and the
      K-index found in this work were compared and found coherent with literature data.
      The performed study reveals the strengths and the suitability of the NMR approach
      to monitor different biochemical processes occurring during fish storage and
      qualitatively and quantitatively characterise fish metabolites determining fish
      quality.

PMID- 25872422
TI  - An iPhone-based digital image colorimeter for detecting tetracycline in milk.
AB  - An iPhone-based digital image colorimeter (DIC) was fabricated as a portable tool
      for monitoring tetracycline (TC) in bovine milk. An application named ColorConc
      was developed for the iPhone that utilizes an image matching algorithm to
      determine the TC concentration in a solution. The color values; red (R), green
      (G), blue (B), hue (H), saturation (S), brightness (V), and gray (Gr) were
      measured from each pictures of the TC standard solutions. TC solution extracted
      from milk samples using solid phase extraction (SPE) was captured and the
      concentration was predicted by comparing color values with those collected in a
      database. The amount of TC could be determined in the concentration range of 0.5
      10 MUg mL(-1). The proposed DIC-iPhone is able to provide a limit of detection
      (LOD) of 0.5 MUg mL(-1) and limit of quantitation (LOQ) of 1.5 MUg mL(-1). The
      enrichment factor was 70 and color of the extracted milk sample was a strong
      yellow solution after SPE. Therefore, the SPE-DIC-iPhone could be used for the
      assay of TC residues in milk at the concentration lower than LOD and LOQ of the
      proposed technique.

PMID- 25872423
TI  - Chemometric classification of Chinese lager beers according to manufacturer based
      on data fusion of fluorescence, UV and visible spectroscopies.
AB  - We report an application of data fusion for chemometric classification of 135
      canned samples of Chinese lager beers by manufacturer based on the combination of
      fluorescence, UV and visible spectroscopies. Right-angle synchronous fluorescence
      spectra (SFS) at three wavelength difference Deltalambda=30, 60 and 80 nm and
      visible spectra in the range 380-700 nm of undiluted beers were recorded. UV
      spectra in the range 240-400 nm of diluted beers were measured. A classification
      model was built using principal component analysis (PCA) and linear discriminant
      analysis (LDA). LDA with cross-validation showed that the data fusion could
      achieve 78.5-86.7% correct classification (sensitivity), while those rates using
      individual spectroscopies ranged from 42.2% to 70.4%. The results demonstrated
      that the fluorescence, UV and visible spectroscopies complemented each other,
      yielding higher synergic effect.

PMID- 25872424
TI  - Effects of various protein- and polysaccharide-based clarification agents on
      antioxidative compounds and colour of pomegranate juice.
AB  - The effects of natural sedimentation and clarification agents [protein-based
      (albumin, casein and gelatin) and polysaccharide-based (chitosan and xanthan
      gum)] on total phenolics, hydrolysable tannins, anthocyanins and antioxidant
      activity of pomegranate juice were investigated. While protein-based agents led
      to higher reductions in the contents of total phenolics (7.2-17.2%), hydrolysable
      tannins (16.7-59.5%) and anthocyanins (11.7-23.7%) (p<0.05) than natural
      sedimentation, polysaccharide-based agents had similar effects on these
      compounds, like natural sedimentation (p>0.05). The stabilities of beta
      punicalagin and alpha-punicalagin (the major hydrolysable tannins) against
      clarification were similar. Moreover, antioxidant activities of the samples
      clarified with polysaccharide-based agents were higher (2.4-26.6%) than those of
      the protein-based agents. For both high total phenolic, hydrolysable tannin and
      anthocyanins contents, as well as high antioxidant activity, we suggest that
      polysaccharide-based agents be used for the clarification of pomegranate juice.
      In fact, chitosan is especially recommended for this purpose since chitosan
      (10.3NTU) led to lower turbidity as compared to xanthan gum (20.0 NTU).

PMID- 25872425
TI  - Development and validation of a triplex real-time PCR assay for the simultaneous
      detection of three mustard species and three celery varieties in food.
AB  - The paper presents a triplex real-time PCR assay allowing the simultaneous
      detection of three mustard species (white, black and brown mustard) and three
      celery varieties (celery roots, celery stalks and leaf celery) in foodstuffs. The
      triplex assay does not show cross-reactivity with other Brassicaceae. Low cross
      reactivities were observed with fenugreek, cumin, ginger, caraway, turmeric,
      lovage and rye, the DeltaCt values were, however, ? 12 compared to positive
      controls. The triplex assay allows the detection of traces of DNA of the
      allergenic components in spite of an excess of the other DNA templates. Analysis
      of extracts from model sausages containing defined concentrations of mustard and
      celery showed that the triplex assay is applicable to both raw and processed
      foods. It was found to allow the detection of 1 ppm black/brown mustard and 50
      ppm white mustard and celery in raw and brewed sausages with a probability ? 95%.

PMID- 25872426
TI  - The impact of beef steak thermal processing on lipid oxidation and postprandial
      inflammation related responses.
AB  - Oxidised lipid species, their bioavailability and impact on inflammatory
      responses from cooked beef steak are poorly characterised. Oxidised lipid species
      from pan-fried (PF) and sous-vide (SV) thermally processed beef were determined
      with UHPLC-ESI/MS. Twenty-three lipid oxidation products increased with thermal
      processing and differences between the PF and SV steaks were measured. Fifteen
      oxidised lipids were measured in post-meal plasma after a cross-over randomised
      clinical study. Postprandial plasma inflammatory markers tended to remain lower
      following the SV meal than the PF meal. High levels of conjugated dienes were
      measured in the HDL fraction, suggesting that the protective effect of HDL may
      extend to the reverse-transport of oxidised lipid species. Oxidised lipids in a
      single meal may influence postprandial oxidative stress and inflammation. Further
      studies are required to examine the lipid oxidative responses to increased
      dietary oxidative lipid load, including the reverse transport activity of HDL. 

PMID- 25871857
TI  - Eighteen New Candidate Effectors of the Phytonematode Heterodera glycines
      Produced Specifically in the Secretory Esophageal Gland Cells During Parasitism.
AB  - Heterodera glycines, the soybean cyst nematode, is the number one pathogen of
      soybean (Glycine max). This nematode infects soybean roots and forms an elaborate
      feeding site in the vascular cylinder. H. glycines produces an arsenal of
      effector proteins in the secretory esophageal gland cells. More than 60 H.
      glycines candidate effectors were identified in previous gland-cell-mining
      projects. However, it is likely that additional candidate effectors remained
      unidentified. With the goal of identifying remaining H. glycines candidate
      effectors, we constructed and sequenced a large gland cell cDNA library resulting
      in 11,814 expressed sequence tags. After bioinformatic filtering for candidate
      effectors using a number of criteria, in situ hybridizations were performed in H.
      glycines whole-mount specimens to identify candidate effectors whose mRNA
      exclusively accumulated in the esophageal gland cells, which is a hallmark of
      many nematode effectors. This approach resulted in the identification of 18 new
      H. glycines esophageal gland-cell-specific candidate effectors. Of these
      candidate effectors, 11 sequences were pioneers without similarities to known
      proteins while 7 sequences had similarities to functionally annotated proteins in
      databases. These putative homologies provided the bases for the development of
      hypotheses about potential functions in the parasitism process. 

PMID- 25872427
TI  - Effect of sodium chloride on the glass transition of condensed starch systems.
AB  - The present investigation deals with the structural properties of condensed
      potato starch-sodium chloride systems undergoing a thermally induced glass
      transition. Sample preparation included hot pressing at 120 degrees C for 7 min
      to produce extensive starch gelatinisation. Materials covered a range of moisture
      contents from 3.6% to 18.8%, which corresponded to relative humidity values of
      11% and 75%. Salt addition was up to 6.0% in formulations. Instrumental work was
      carried out with dynamic mechanical analysis in tension, modulated differential
      scanning calorimetry, Fourier transform infrared spectroscopy, scanning electron
      microscopy and wide angle X-ray diffraction. Experimental conditions ensured the
      development of amorphous matrices that exhibited thermally reversible glassy
      consistency. Both moisture content and addition of sodium chloride affected the
      mechanical strength and glass transition temperature of polymeric systems. Sodium
      ions interact with chemical moieties of the polysaccharide chain to alter
      considerably structural properties, as compared to the starch-water matrix.

PMID- 25872428
TI  - Sensitive detection of beta-agonists in pork tissue with novel molecularly
      imprinted polymer extraction followed liquid chromatography coupled tandem mass
      spectrometry detection.
AB  - A novel molecularly imprinted polymer micro-spheres (MIPMs) with
      phenylethanolamine A as the template and the p-vinylbenzoic acid as the
      functional monomer were synthesized for the selective absorption of clenbuterol
      and other beta-agonists including brombuterol, bromchlorbuterol, clorprenaline
      and ractopamine. The absorption performances of the MIPMs were studied and the
      experimental results demonstrated that the extraction capacities of five beta
      agonists with MIPMs were about from 2.7 to 3.4 times as much as that with non
      imprinted polymer micro-spheres. Based on the clean-up of five beta-agonists in
      pork tissues with MIPMs, a sensitive determination method for five beta-agonists
      coupled with ultra performance chromatography coupled tandem mass spectrometry
      detection has been developed. The limits of detection for five beta-agonists were
      <0.02 MUg/kg. The mean recoveries and repeatability of five beta-agonists in pork
      tissues varied from 70.0% to 116.0% and from 2.5% to 10.4%, respectively. The
      developed method was successfully applied to analysis of 22 real pork tissues
      samples.

PMID- 25872430
TI  - Influence of light exposure and oxidative status on the stability of vitamins A
      and D3 during the storage of fortified soybean oil.
AB  - Food fortification is implemented to address vitamins A and D deficiencies in
      numerous countries. The stability of vitamins A and D3 was assessed during a two
      month period reproducing the usual oil storage conditions before sale to
      consumers. Soybean oils with different oxidative status and vitamin E contents
      were stored in the dark, semi-dark, or exposed to natural light. Lipid
      peroxidation took place after 3 weeks of storage in dark conditions. After 2
      months, the vitamin A and D3 losses reached 60-68% and 61-68%, respectively, for
      oils exposed to natural light, and 32-39% and 24-44% in semi-dark conditions. The
      determining factors of vitamin A and D3 losses were (in decreasing order) the
      storage time, the exposure to light and the oxidative status of the oil, whereas
      vitamin E content had a protective role. Improving these parameters is thus
      essential to make vitamins A and D fortification in oils more efficient.

PMID- 25872429
TI  - Optimization of ultrasound-assisted extraction of antioxidant compounds from
      Tunisian Zizyphus lotus fruits using response surface methodology.
AB  - The optimization of antioxidant extraction conditions from a ripe edible fruits
      of Zizyphus lotus (L.) with an ultrasound-assisted system was achieved by
      response surface methodology. The central composite rotatable design was employed
      for optimization of extraction parameters in terms of total phenolic content and
      antioxidant activities using 2,2-diphenyl-1-picrylhydrazyl radical scavenging
      activity and phosphomolybdenum assay. The optimum operating conditions for
      extraction were as follows: ethanol concentration, 50%; extraction time, 25 min;
      extraction temperature, 63 degrees C and ratio of solvent to solid, 67 mL/g.
      Under these conditions, the obtained extract exhibited a high content of phenolic
      compounds (40.782 mg gallic acid equivalents/g dry matter) with significant
      antioxidant properties (the total antioxidant activity was 75.981 mg gallic acid
      equivalents/g dry matter and the 2,2-diphenyl-1-picrylhydrazyl radical scavenging
      activity was 0.289 mg/mL).

PMID- 25872432
TI  - Physicochemical properties of peanut oil-based diacylglycerol and their derived
      oil-in-water emulsions stabilized by sodium caseinate.
AB  - High purity peanut oil-based diacylglycerol (PO-DAG) (94.95 wt%) was prepared via
      enzymatic glycerolysis from peanut oil (PO). The resulting dominance of DAGs was
      proven to greatly influence the properties of corresponding fresh or frozen
      thawed emulsions. Stable fresh oil-in-water emulsions were produced using either
      PO-DAG or PO, with stability enhanced by increased concentrations of Na-CN. The
      lower equilibrium interfacial tension along with greater negative zeta-potential
      of PO revealed that Na-CN was preferentially adsorbed to the PO interface. Adding
      0.05 mol/L NaCl to the PO emulsions minimized depletion flocculation caused by
      the unadsorbed Na-CN, but further NaCl addition increased oil droplet size and
      concomitant coalescence. For the PO-DAG emulsions, adding 0.2 mol/L NaCl did not
      significantly (p>0.05) affect their zeta-potential but adding 0.05 or 0.1 mol/L
      NaCl lowered zeta-potential, although NaCl at these concentrations increased oil
      droplet size and coalescence. Freezing-thawing process considerably weakened the
      stability of PO-DAG emulsions.

PMID- 25872433
TI  - Effects of high-hydrostatic pressure and pH treatments on the emulsification
      properties of gum arabic.
AB  - This study investigated the emulsification properties of the native gums and
      those treated at high pressure (800 MPa) both at their "natural" pH (4.49 and
      4.58, respectively) and under "acidic and basic" pH (2.8 and 8.0) conditions. The
      emulsification behaviour of KLTA gum was found to be superior to that of the GCA
      gum. High pressure and pH treatment changed the emulsification properties of both
      gums. The acidic amino acids in gum arabic were shown to play an important role
      in their emulsification behaviour, and mechanisms of emulsification for the two
      gums were suggested to be different. The highly "branched" nature of the
      carbohydrate in GCA gum was also thought to be responsible for the "spreading" of
      droplet size distributions observed. Coomassie brilliant blue binding was used to
      indicate conformational changes in protein structure and Ellman's assay was used
      to estimate any changes in levels of free thiols present.

PMID- 25872431
TI  - Preparation and characterization of inclusion complex of benzyl isothiocyanate
      extracted from papaya seed with beta-cyclodextrin.
AB  - The inclusion complex of benzyl isothiocyanate (BITC), extracted from papaya seed
      with beta-cyclodextrin (beta-CD), was prepared. Different analytical techniques,
      such as Fourier transform infrared spectroscopy, thermal analysis, X-ray
      diffractometry, particle size distribution analysis and (1)H Nuclear magnetic
      resonance analysis, were used to investigate the characterization of the
      inclusion complex (BITC-beta-CD). All these approaches indicated that the
      inclusion complex was capable of being formed. The inclusion complex exhibited
      different spectroscopic and thermodynamic features and properties from BITC, and
      we deduced the possible inclusion modes for BITC-beta-CD. The calculated apparent
      stability constant of the BITC-beta-CD was 600.8l/mol, and the aqueous solubility
      of BITC was indistinctively improved by phase solubility studies. The results
      illustrated that beta-CD was a proper excipient for increasing the stability and
      controlled release of BITC. Thus, beta-CD complexation technology would be a
      promising approach, in expanding the application of BITC as a food antibacterial
      agent. 

PMID- 25872434
TI  - Effect of Stevia rebaudiana addition on bioaccessibility of bioactive compounds
      and antioxidant activity of beverages based on exotic fruits mixed with oat
      following simulated human digestion.
AB  - In order to determine the impact of Stevia rebaudiana (SR) addition on bioactive
      compounds bioaccessibility of a new developed functional beverage based on exotic
      fruits (mango juice, papaya juice and acai) mixed with orange juice and oat, an
      in vitro gastrointestinal digestion was performed. Ascorbic acid, total
      carotenoids, total phenolics, total anthocyanins, total antioxidant capacity and
      steviol glycosides were evaluated before and after a simulated gastrointestinal
      digestion. Salivary and gastric digestion had no substantial effect on any of the
      major phenolic compounds, ascorbic acid, total antioxidant capacity and steviol
      glycosides, whereas carotenoids and anthocyanins diminished significantly during
      the gastric step. All analysed compounds were significantly altered during the
      pancreatic-bile digestion and this effect was more marked for carotenoids and
      total anthocyanins. However, phenolic compounds, anthocyanins, total antioxidant
      capacity and steviol glycosides bioaccessibility increased as did SR
      concentration. Ascorbic acid bioaccessibility was negatively affected by the SR
      addition. 

PMID- 25872435
TI  - Accelerated solvent extraction of carotenoids from: Tunisian Kaki (Diospyros kaki
      L.), peach (Prunus persica L.) and apricot (Prunus armeniaca L.).
AB  - Extraction of carotenoids from biological matrices and quantifications remains a
      difficult task. Accelerated solvent extraction was used as an efficient
      extraction process for carotenoids extraction from three fruits cultivated in
      Tunisia: kaki (Diospyros kaki L.), peach (Prunus persica L.) and apricot (Prunus
      armeniaca L.). Based on a design of experiment (DoE) approach, and using a binary
      solvent consisting of methanol and tetrahydrofuran, we could identify the best
      extraction conditions as being 40 degrees C, 20:80 (v:v) methanol/tetrahydrofuran
      and 5 min of extraction time. Surprisingly and likely due to the high extraction
      pressure used (103 bars), these conditions appeared to be the best ones both for
      extracting xanthophylls such as lutein, zeaxanthin or beta-cryptoxanthin and
      carotenes such as beta-carotene, which present quite different polarities. Twelve
      surface responses were generated for lutein, zeaxanthin, beta-cryptoxanthin and
      beta-carotene in kaki, peach and apricot. Further LC-MS analysis allowed
      comparisons in carotenoids profiles between the fruits.

PMID- 25872436
TI  - Identification of short peptide sequences in complex milk protein hydrolysates.
AB  - Numerous low molecular mass bioactive peptides (BAPs) can be generated during the
      hydrolysis of bovine milk proteins. Low molecular mass BAP sequences are less
      likely to be broken down by digestive enzymes and are thus more likely to be
      active in vivo. However, the identification of short peptides remains a challenge
      during mass spectrometry (MS) analysis due to issues with the transfer and over
      fragmentation of low molecular mass ions. A method is described herein using time
      of-flight ESI-MS/MS to effectively fragment and identify short peptides. This
      includes (a) short synthetic peptides, (b) short peptides within a defined
      hydrolysate sample, i.e. a prolyl endoproteinase hydrolysate of beta-casein and
      (c) short peptides within a complex hydrolysate, i.e. a Corolase PP digest of
      sodium caseinate. The methodology may find widespread utilisation in the
      efficient identification of low molecular mass peptide sequences in food protein
      hydrolysates. 

PMID- 25872437
TI  - Rapid extraction and reverse phase-liquid chromatographic separation of
      mercury(II) and methylmercury in fish samples with inductively coupled plasma
      mass spectrometric detection applying oxygen addition into plasma.
AB  - A simple and sensitive procedure was developed for extraction and speciation of
      mercury in fish. Species separation was accomplished with reverse phase-high
      performance liquid chromatography (HPLC) hyphenated to inductively coupled plasma
      mass spectrometry (ICP-MS). Oxygen addition into plasma allowed use of organic
      rich mobile phase, achieving species separation in 4 min. Mercury species
      extraction was achieved by microwave exposure for 2 min at mild conditions (60
      degrees C, pH 2.0), avoiding necessity of neutralizing sample prior to injection
      in HPLC, and reducing number of sample preparation steps, analytical source of
      errors and inter conversion of species. Limit of detection for entire procedure
      was found to be 0.2 and 0.1 ng g(-1) for mercuric ion and methylmercury,
      respectively. The method was applied to certified reference materials (TORT-2 and
      DORM-2) and commercialized fish samples (Mullus barbatus, Sparus aurata,
      Trachurus mediterraneus, Mugil soiuy, Dicentrarchus labrax, and Pomatomus
      saltatrix) from Black Sea.

PMID- 25872438
TI  - A simple and practical control of the authenticity of organic sugarcane samples
      based on the use of machine-learning algorithms and trace elements determination
      by inductively coupled plasma mass spectrometry.
AB  - A practical and easy control of the authenticity of organic sugarcane samples
      based on the use of machine-learning algorithms and trace elements determination
      by inductively coupled plasma mass spectrometry is proposed. Reference ranges for
      32 chemical elements in 22 samples of sugarcane (13 organic and 9 non organic)
      were established and then two algorithms, Naive Bayes (NB) and Random Forest
      (RF), were evaluated to classify the samples. Accurate results (>90%) were
      obtained when using all variables (i.e., 32 elements). However, accuracy was
      improved (95.4% for NB) when only eight minerals (Rb, U, Al, Sr, Dy, Nb, Ta, Mo),
      chosen by a feature selection algorithm, were employed. Thus, the use of a
      fingerprint based on trace element levels associated with classification machine
      learning algorithms may be used as a simple alternative for authenticity
      evaluation of organic sugarcane samples. 

PMID- 25872439
TI  - Identification of novel allergen in edible insect, Gryllus bimaculatus and its
      cross-reactivity with Macrobrachium spp. allergens.
AB  - Edible insects have recently been promoted as a source of protein and have a high
      nutrition value. Identification of allergens and cross-reactivity between
      Macrobrachium spp. and the field cricket (Gryllus bimaculatus) is necessary for
      food safety control and to assist in the diagnosis and therapy of allergy
      symptoms. Denaturing polyacrylamide gel electrophoresis (SDS-PAGE) was used to
      separate proteins. Allergens were determined and identified by IgE-immunoblotting
      with pooled sera from prawn-allergic patients (n=16) and LC-MS/MS. Arginine
      kinase (AK) and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) were determined
      as the important allergens in muscle of Macrobrachium rosenbergii whereas,
      hemocyanin (HC) was identified as an allergen in Macrobrachium spp. The allergens
      in Macrobrachium lanchesteri were identified as AK and HC. In addition,
      hexamerin1B (HEX1B) was identified as a novel and specific allergen in G.
      bimaculatus. The important allergen in G. bimaculatus and Macrobrachium spp. is
      AK and was found to cross-react between both species. 

PMID- 25872440
TI  - Effects of electrospun chitosan wrapping for dry-ageing of beef, as studied by
      microbiological, physicochemical and low-field nuclear magnetic resonance
      analysis.
AB  - The effects of using electrospun chitosan fibres as a wrapping material for dry
      ageing beef was studied and compared to traditional dry-ageing and wet-ageing of
      beef for up to 21 days. The chitosan treatment showed improved results in terms
      of yield, reduction of microbial counts, yeasts and moulds, and lighter
      appearance compared to traditional dry-ageing. Weight and trimming losses were
      minimal in the wet-ageing beef. However, significant growth of lactic acid
      bacteria was observed in this group. Transverse relaxation times indicated a
      lower degree of muscle denaturation during ageing in the chitosan dry-ageing beef
      compared to the traditional dry-ageing meat. A principal component analysis
      furthermore indicated that 60.6% of the variation between samples and ageing
      treatments could be described by differences in the water content and
      distribution in the muscle. The study showed that electrospun chitosan fibre mats
      have potential as a wrapping material for improved quality during dry-ageing of
      beef.

PMID- 25872441
TI  - Synthesis and application of cephalexin imprinted polymer for solid phase
      extraction in milk.
AB  - Molecular imprinted polymer (MIP) against cephalexin was synthesized by co
      polymerization of functional monomer, cross-linker, radical initiator, along with
      target molecule (cephalexin) in a porogenic material. Binding of cephalexin
      towards prepared MIP was studied in different solvents (water, methanol, 1M NaCl,
      acetone and acetonitrile) and best binding was observed in methanol. Partition
      coefficient and selectivity of prepared imprint and non-imprint was also studied.
      Cross reactivity in terms of binding efficiency was also assessed with other
      antibiotics. Chromatographic study of MIP was carried out by packing prepared
      imprint into glass column. MIP was used as matrix in solid phase extraction (SPE)
      for recovery of cephalexin from spiked milk samples for further estimation by
      high performance liquid chromatography. No interference was observed from milk
      components after elution of cephalexin from MIP, indicating selectivity and
      affinity of MIP. On the other hand, interference was observed in eluate obtained
      from C18 SPE column. 

PMID- 25872442
TI  - Electrochemical assay for determination of gluten in flour samples.
AB  - Herein, an electrochemical assay developed by differential pulse voltammetry
      (DPV) in combination with the disposable pencil graphite electrode (PGE) was
      progressed for sensitive and selective detection of gluten. Under the optimum
      experimental conditions, a linear concentration range of gluten was obtained from
      20 to 100 MUg/mL and consequently the detection limit was found to be 7.11
      MUg/mL. In addition, this electrochemical assay was successfully employed for the
      detection of gluten in different flour samples. Applicability of our method was
      also tested in the commercial samples of vinegar and baker's yeast.

PMID- 25872443
TI  - Selective microextraction of mononucleotides from milk using alumina and stannia
      hollow fibers prior to their determination by hydrophilic interaction liquid
      chromatography-diode array detection.
AB  - Alumina- and stannia-based hollow fibers were synthesized via simple sol-gel
      procedures and characterized with respect to morphology, crystalline phase and
      specific surface area. Then, an optimization study was undertaken for the
      preconcentration of five 5'-mononucleotides using the hollow fibers. The
      separation and quantification of the analytes were carried out by HILIC with
      diode array detection, after proper optimization of the chromatographic
      conditions. The method demonstrated satisfactory linearities over a concentration
      range of 0.09-50 MUg mL(-1) with regression coefficients to range from 0.9993 to
      0.9997. A range of commercially available 5'-mononucleotide supplemented infant
      formulas and three human breast milk samples were used to apply alumina hollow
      fibers, as a proof of concept. Recoveries ranged from 84% to 104%, while the
      calculated RSDs were from 3.6% to 4.3%. The proposed preconcentration-clean-up
      method is environmentally friendly and convenient, indicating that alumina and
      stannia are suitable for the applications by immersing them into milk samples,
      after removal of proteins.

PMID- 25872444
TI  - Variation of bioactive compounds content of 14 oriental strawberry cultivars.
AB  - Variation in bioactive compounds content was assessed in antioxidant rich June
      bearing strawberry cultivars. Ascorbic acid, anthocyanin, and ellagic acid
      content were analyzed in ripe fruits of 14 cultivars. The bioactive content in
      strawberry fruit was found to vary significantly among cultivars and from year to
      year. The highest ascorbic acid content was found in 'Sugyeong'. The 'Red Pearl'
      and 'Sachinoka' had three to fourfold higher amounts of pelargonidin 3-glucoside
      than other cultivars. For cyanidin 3-glucoide and pelargonidin 3-rutinoside, two
      other characterized anthocyanins, 'Dahong' and 'Keumhyang' had the highest
      contents among all the tested cultivars. The ellagic acid content of 'Dahong' was
      generally all within the upper ranges. These results can be used for the
      validation of fruit antioxidant capacity and in addition, provide useful
      information for breeding programs looking to enhance the antioxidant capacity in
      strawberry fruit. 

PMID- 25872445
TI  - Halal authenticity of gelatin using species-specific PCR.
AB  - Consumption of food products derived from porcine sources is strictly prohibited
      in Islam. Gelatin, mostly derived from bovine and porcine sources, has many
      applications in the food and pharmaceutical industries. To ensure that food
      products comply with halal regulations, development of valid and reliable
      analytical methods is very much required. In this study, a species-specific
      polymerase chain reaction (PCR) assay using conserved regions of mitochondrial
      DNA (cytochrome b gene) was performed to evaluate the halal authenticity of
      gelatin. After isolation of DNA from gelatin powders with known origin,
      conventional PCR using species-specific primers was carried out on the extracted
      DNA. The amplified expected PCR products of 212 and 271 bp were observed for
      porcine and bovine gelatin, respectively. The sensitivity of the method was
      tested on binary gelatin mixtures containing 0.1%, 1%, 10%, and 100% (w/w) of
      porcine gelatin within bovine gelatin and vice versa. Although most of the DNA is
      degraded due to the severe processing steps of gelatin production, the minimum
      level of 0.1% w/w of both porcine and bovine gelatin was detected. Moreover,
      eight food products labeled as containing bovine gelatin and eight capsule shells
      were subjected to PCR examination. The results showed that all samples contained
      bovine gelatin, and the absence of porcine gelatin was verified. This method of
      species authenticity is very useful to verify whether gelatin and gelatin
      containing food products are derived from halal ingredients.

PMID- 25872446
TI  - Oxidative stability of n-3 fatty acids encapsulated in filled hydrogel particles
      and of pork meat systems containing them.
AB  - The effect of storage time (2 degrees C, 19 days) and heating (70 degrees C, 30
      min) on physical characteristics and oxidative stability of fish oil encapsulated
      in filled hydrogel particles was determined and compared with a conventional oil
      in-water (O/W) emulsion with the same oil content (8.5%). Subsequently they were
      used to enrich meat systems with n-3 LCPUFAs, and their lipid oxidation was
      evaluated and compared with two other meat systems: one containing all animal fat
      and another with fish oil added directly. Filled hydrogel particles were more
      effective in lowering the oxidation rate than O/W emulsion, even when thermal
      treatment was applied. Oxidative stability over the storage time was best in the
      n-3 LCPUFA-enriched meat system containing filled hydrogel particles, in which
      TBARS levels were up to 62% lower than other systems containing fish oil.
      Hydrogel particles offer a promising means of controlling lipid oxidation in n-3
      LCPUFA-enriched meat products.

PMID- 25872447
TI  - Modeling excitation-emission fluorescence matrices with pattern recognition
      algorithms for classification of Argentine white wines according grape variety.
AB  - This paper reports the modeling of excitation-emission matrices for
      classification of Argentinean white wines according to the grape variety
      employing chemometric tools for pattern recognition. The discriminative power of
      the data was first investigated using Principal Component Analysis (PCA) and
      Parallel Factor Analysis (PARAFAC). The score plots showed strong overlapping
      between classes. A forty-one samples set was partitioned into training and test
      sets by the Kennard-Stone algorithm. The algorithms evaluated were SIMCA, N- and
      U-PLS-DA and SPA-LDA. The fit of the implemented models was assessed by mean of
      accuracy, sensitivity and specificity. These models were then used to assign the
      type of grape of the wines corresponding to the twenty samples test set. The best
      results were obtained for U-PLS-DA and SPA-LDA with 76% and 80% accuracy. 

PMID- 25872448
TI  - Characterization of extra virgin olive oils produced with typical Italian
      varieties by their phenolic profile.
AB  - Evaluation of phenolic profile, antioxidant power, and protective capacity
      against oxidation of red blood cells (RBCs) of olive oil phenolic extracts
      (OOPEs) from several Italian varieties were studied. Phenolic profiles, and
      quantification of seven selected bioactive compounds were performed by RP-HPLC.
      OOPEs exhibited high antioxidant activity, and this capacity was positively
      related to their phenolic amount. In particular, OOPE5 (cv Gentile di Larino,
      Molise region) displayed the highest phenolic and ortho-diphenolic content as
      well as the strongest scavenging activity determined using 2,2'-diphenyl-1
      picrylhydrazyl (DPPH) (87% DPPH inhibition). Protective capacity against stressed
      RBCs was investigated through the evaluation of methemoglobin (MetHb) and
      malondialdehyde (MDA) levels. OOPE5 was the most active against methemoglobin
      production (53.7% reduction), whereas OOPE1 (cv Lavagnina, Liguria region) showed
      the highest protection toward malondialdehyde (83.3% reduction). Overall the
      selected oils showed qualitative and quantitative differences in phenol
      composition, and this variability influenced their protective effect against
      oxidative damages. 

PMID- 25872449
TI  - Modelling the Maillard reaction during the cooking of a model cheese.
AB  - During processing and storage of industrial processed cheese, odorous compounds
      are formed. Some of them are potentially unwanted for the flavour of the product.
      To reduce the appearance of these compounds, a methodological approach was
      employed. It consists of: (i) the identification of the key compounds or
      precursors responsible for the off-flavour observed, (ii) the monitoring of these
      markers during the heat treatments applied to the cheese medium, (iii) the
      establishment of an observable reaction scheme adapted from a literature survey
      to the compounds identified in the heated cheese medium (iv) the multi-responses
      stoichiokinetic modelling of these reaction markers. Systematic two-dimensional
      gas chromatography time-of-flight mass spectrometry was used for the semi
      quantitation of trace compounds. Precursors were quantitated by high-performance
      liquid chromatography. The experimental data obtained were fitted to the model
      with 14 elementary linked reactions forming a multi-response observable reaction
      scheme. 

PMID- 25872450
TI  - Comparative study of flavonoid production in lycopene-accumulated and blonde
      flesh sweet oranges (Citrus sinensis) during fruit development.
AB  - Four main flavanone glycosides (FGs) and four main polymethoxylated flavones
      (PMFs) were determined in fruits of 'Cara Cara' navel orange, 'Seike' navel
      orange, 'Anliu' and 'Honganliu' sweet orange (Citrus sinensis). No bitter
      neohesperidosides were detected in the FG profiles, indicating the functional
      inability of 1,2-rhamnosyltransferase, though relatively high transcription
      levels were detected in the fruit tissues of 'Anliu' and 'Honganliu' sweet
      oranges. Different to the FGs, the PMFs only exist abundantly in the peel and
      decreased gradually throughout fruit development of sweet oranges, suggesting the
      expression of methylation-related genes accounting for PMF biosynthesis have
      tissue-specificity. Significant changes in production of the eight flavonoids
      were found between red-flesh and blonde-flesh sweet oranges, indicating that
      lycopene accumulation might have direct or indirect effects on the modification
      of flavonoid biosynthesis in these citrus fruits.

PMID- 25872452
TI  - Endometrial ILKAP expression among patients with endometriosis and its
      association with clinical characteristics.
AB  - OBJECTIVE: To investigate expression of ILKAP among women with endometriosis and
      its association with clinical characteristics. METHODS: A retrospective study was
      conducted at a center in China in 2012, using samples of ectopic (n=55) and
      eutopic (n=33) endometrium from women with endometriosis, and control endometrium
      samples (n=33) from women without endometriosis. Information on clinical
      characteristics was obtained from records. The expression of ILKAP was tested by
      immunohistochemistry. RESULTS: The expression of ILKAP was higher in the
      secretory phase of the menstrual cycle than in the proliferative phase, and it
      was lower in eutopic and ectopic endometriosis tissue than in control endometrium
      (P<0.001 for both). A lower expression of ILKAP in ectopic endometrium was
      associated with moderate-to-severe dysmenorrhea, infertility for more than 1year,
      a cancer antigen 125 level of more than 35 U/mL, a disease duration of at least
      1year, and American Fertility Society grade IV disease (P<0.05 for all).
      CONCLUSION: A low level of ILKAP could facilitate the pathogenesis of
      endometriosis. Additionally, the level of ILKAP expression in ectopic endometrium
      might reflect the severity of endometriosis.

PMID- 25872451
TI  - miR-1269 promotes metastasis and forms a positive feedback loop with TGF-beta.
AB  - As patient survival drops precipitously from early-stage cancers to late-stage
      and metastatic cancers, microRNAs that promote relapse and metastasis can serve
      as prognostic and predictive markers as well as therapeutic targets for
      chemoprevention. Here we show that miR-1269a promotes colorectal cancer (CRC)
      metastasis and forms a positive feedback loop with TGF-beta signalling. miR-1269a
      is upregulated in late-stage CRCs, and long-term monitoring of 100 stage II CRC
      patients revealed that miR-1269a expression in their surgically removed primary
      tumours is strongly associated with risk of CRC relapse and metastasis.
      Consistent with clinical observations, miR-1269a significantly increases the
      ability of CRC cells to invade and metastasize in vivo. TGF-beta activates miR
      1269 via Sox4, while miR-1269a enhances TGF-beta signalling by targeting Smad7
      and HOXD10, hence forming a positive feedback loop. Our findings suggest that miR
      1269a is a potential marker to inform adjuvant chemotherapy decisions for CRC
      patients and a potential therapeutic target to deter metastasis. 

PMID- 25872453
TI  - Fetal and neonatal outcomes after term and preterm delivery following
      betamethasone administration.
AB  - OBJECTIVE: To determine the effects of betamethasone on fetal growth and neonatal
      outcomes. METHODS: A retrospective cohort study was performed of deliveries that
      occurred at Charite University Hospital Berlin, Germany, between January 1996 and
      December 2008. The betamethasone group included women with preterm labor and
      symptomatic contractions, cervical insufficiency, preterm premature rupture of
      membranes, or vaginal bleeding. Women in the control group were matched for
      gestational age at time of delivery and had not received betamethasone. Fetal
      growth changes and neonatal anthropometry were compared. RESULTS: Among 1799
      newborns in the betamethasone group and 42 240 in the control group,
      betamethasone was associated with significantly lower birth weight (154 g lower
      on average) after adjusting for confounders (e.g. hypertension, smoking, and
      maternal weight), sex, and gestational age at delivery (P<0.05). The higher the
      dose, the greater the difference in mean birth weight versus controls in births
      before 34(+0)weeks (<=16 mg -444 g; 24 mg -523 g; >24 mg -811 g), without a
      detectable improvement in neonatal morbidity or mortality. There was a dose
      dependent decline in expected fetal weight gain as estimated by serial
      ultrasonography examinations 6-8 weeks after betamethasone administration
      (P<0.05). CONCLUSION: Betamethasone exposure reduces fetal weight gain in a dose
      dependent manner without improving neonatal morbidity or mortality.

PMID- 25872454
TI  - One-process fabrication of metal hierarchical nanostructures with rich nanogaps
      for highly-sensitive surface-enhanced Raman scattering.
AB  - One-process fabrication of highly active and reproducible surface-enhanced Raman
      scattering (SERS) substrates via ion beam deposition is reported. The fabricated
      metal-dielectric-metal (MDM) hierarchical nanostructure possesses rich nanogaps
      and a tunable resonant cavity. Raman scattering signals of analytes are
      dramatically strengthened due to the strong near-field coupling of localized
      surface plasmon resonances (LSPRs) and the strong interaction of LSPRs of metal
      NPs with surface plasmon polaritons (SPPs) on the underlying metal film by
      crossing over the dielectric spacer. The maximum Raman enhancement for the
      highest Raman peak at 1650 cm(-1) is 13.5 times greater than that of a single
      metal nanoparticle (NP) array. Moreover, the SERS activity can be efficiently
      tailored by varying the size and number of voids between adjacent metal NPs and
      the thickness of the dielectric spacer. These findings may broaden the scope of
      SERS applications of MDM hierarchical nanostructures in biomedical and analytical
      chemistry. 

PMID- 25872455
TI  - Tailoring of interfacial mechanical shear strength by surface chemical
      modification of silicon microwires embedded in Nafion membranes.
AB  - The interfacial shear strength between Si microwires and a Nafion membrane has
      been tailored through surface functionalization of the Si. Acidic (-COOH
      terminated) or basic (-NH2-terminated) surface-bound functionality was introduced
      by hydrosilylation reactions to probe the interactions between the functionalized
      Si microwires and hydrophilic ionically charged sites in the Nafion polymeric
      side chains. Surfaces functionalized with SiOx, Si-H, or Si-CH3 were also
      synthesized and investigated. The interfacial shear strength between the
      functionalized Si microwire surfaces and the Nafion matrix was quantified by
      uniaxial wire pull-out experiments in an in situ nanomechanical instrument that
      allowed simultaneous collection of mechanical data and visualization of the
      deformation process. In this process, an axial load was applied to the custom
      shaped top portions of individual wires until debonding occurred from the Nafion
      matrix. The shear strength obtained from the nanomechanical measurements
      correlated with the chemical bond strength and the functionalization density of
      the molecular layer, with values ranging from 7 MPa for Si-CH3 surfaces to ~16-20
      MPa for oxygen-containing surface functionalities. Hence surface chemical control
      can be used to influence the mechanical adhesion forces at a Si-Nafion interface.

PMID- 25872456
TI  - What's left in language? Beyond the classical model.
AB  - Until recently it was widely held that language, and its left-hemispheric
      representation in the brain, were uniquely human, emerging abruptly after the
      emergence of Homo sapiens. Changing views of language suggest that it was not a
      recent and sudden development in human evolution, but was adapted from dual
      stream circuity long predating hominins, including a system in nonhuman primates
      specialized for intentional grasping. This system was gradually tailored for
      skilled manual operations (praxis) and communication. As processing requirements
      grew more demanding, the neural circuits were increasingly lateralized, with the
      left hemisphere assuming dominance, at least in the majority of individuals. The
      trend toward complexity and lateralization was probably accelerated in hominins
      when bipedalism freed the hands for more complex manufacture and tool use, and
      more expressive communication. The incorporation of facial and vocal gestures led
      to the emergence of speech as the dominant mode of language, although gestural
      communication may have led to generative language before speech became dominant.
      This scenario provides a more Darwinian perspective on language and its
      lateralization than has been commonly assumed. 

PMID- 25872457
TI  - Evaluation of DEM-DISC, customized e-advice on health and social support services
      for informal carers and case managers of people with dementia; a cluster
      randomized trial.
AB  - BACKGROUND: Few personalized e-interventions are available for informal and
      professional caregivers of people with dementia. The DEMentia Digital Interactive
      Social Chart (DEM-DISC) is an ICT tool to support customized disease management
      in dementia. The aim of this study was to improve and evaluate DEM-DISC, its user
      friendliness and usefulness and to investigate the future implementation.
      METHODS: A cluster randomized controlled trial (RCT) design was used with
      measurements at baseline, 6 and 12 months. A total of 73 informal caregivers of
      people with dementia, supported by 19 randomized case managers participated in
      the study. In the intervention group, both carers (n = 41) and case managers (n =
      13) could access DEM-DISC during twelve months. The control group, 32 carers and
      14 case managers, had no access to DEM-DISC. Semi-structured interviews were
      conducted with ten stakeholders. RESULTS: Informal caregivers who used DEM-DISC
      for twelve months reported an increased sense of competence than controls. A
      subgroup of users who frequently accessed DEM-DISC reported more met needs after
      six months than controls. Overall informal caregivers and case managers judged
      DEM-DISC as easy to learn and user-friendly. CONCLUSIONS: This study demonstrates
      that using DEM-DISC had a positive effect on the sense of competence and
      experienced (met) needs of informal carers. This shows the importance of user
      friendly ICT solutions to assist carers in finding appropriate care services
      tailored to their specific situation and needs. For further implementation of DEM
      DISC methods to keep the information updated is of great importance.

PMID- 25872458
TI  - Facile one-pot synthesis of multi-yolk-shell Bi@C nanostructures by the nanoscale
      Kirkendall effect.
AB  - Multi-yolk-shell Bi@C nanostructures were prepared via a facile one-pot template
      free hydrothermal approach. The prepared Bi@C nanostructures can act as a solid
      catalyst in the thermal decomposition of cyclotrimethylenetrinitramine (RDX) and
      display excellent catalytic activity, which highlights their application in the
      field of energetic materials. 

PMID- 25872459
TI  - Sulfasalazine disposition in a subject with 376C>T (nonsense mutation) and 421C>A
      variants in the ABCG2 gene.

PMID- 25872460
TI  - Learning Patient Safety in Academic Settings: A Comparative Study of Finnish and
      British Nursing Students' Perceptions.
AB  - BACKGROUND: Globalization of health care demands nursing education programs that
      equip students with evidence-based patient safety competences in the global
      context. Nursing students' entrance into clinical placements requires
      professional readiness. Thus, evidence-based learning activities about patient
      safety must be provided in academic settings prior to students' clinical
      placements. AIMS: To explore and compare Finnish and British nursing students'
      perceptions of learning about patient safety in academic settings to inform
      nursing educators about designing future education curriculum. METHODS: A purpose
      designed instrument, Patient Safety in Nursing Education Questionnaire (PaSNEQ)
      was used to examine the perceptions of Finnish (n = 195) and British (n = 158)
      nursing students prior to their final year of registration. Data were collected
      in two Finnish and two English nursing schools in 2012. Logistic regressions were
      used to analyze the differences. RESULTS: British students reported more
      inclusion (p < .001) of "gaining knowledge," "training skills," and "highlighting
      affirmative attitudes and motivation" related to patient safety in their
      programs. Both student groups considered patient safety education to be more
      valuable for their own learning than what their programs had provided. Training
      patient safety skills in the academic settings were the strongest predictors for
      differences (odds ratio [OR] = 34.69, 95% confidence interval [CI] 7.39-162.83),
      along with work experience in the healthcare sector (OR = 3.02, 95% CI 1.39
      6.58). LINKING EVIDENCE TO ACTION: To prepare nursing students for practical
      work, training related to clear communication, reporting errors, systems-based
      approaches, interprofessional teamwork, and use of simulation in academic
      settings requires comprehensive attention, especially in Finland. Overall,
      designing patient safety-affirming nursing curricula in collaboration with
      students may enhance their positive experiences on teaching and learning about
      patient safety. An international collaboration between educators could help to
      develop and harmonize patient safety education and to better prepare nurses for
      practice in the global context.

PMID- 25872461
TI  - Effect of compositional and antisite disorder on the electronic and magnetic
      properties of Ni-Mn-In Heusler alloy.
AB  - A systematic study has been done on the electronic and magnetic properties of
      metamagnetic Ni-Mn-In Heusler alloy with compositional and structural (anti-site)
      disorder at high temperature austenite phase. The electronic structure
      calculation shows an increasing Mn-Ni hybridization which occurs due to the
      decrease in Mn-Ni bond length as the system approaches martensite phase. The
      results obtained from magnetic moment calculations follow a similar trend to the
      previous experimental and theoretical results. The magnetic coupling parameters,
      Jij, obtained from the ab initio calculation explains the presence of competing
      ferromagnetic (FM) and antiferromagnetic (AFM) interactions in the system and the
      dominating AFM interactions nearer to the martensite phase. 

PMID- 25872463
TI  - Clinical news.

PMID- 25872462
TI  - Circulating endothelial progenitor cells and angiogenic factors in diabetes
      complicated diabetic foot and without foot complications.
AB  - INTRODUCTION: Data about angiogenic factors in diabetic foot syndrome (DFS) are
      insufficient. Therefore, in the present study we focus on circulating endothelial
      progenitor cells (EPCs) and two major angiogenic factors: vascular endothelial
      growth factor (VEGF-A) and fibroblast growth factor (FGF-2) in patients with DFS.
      MATERIALS AND METHODS: We included 75 subjects: 45 patients with type 2 diabetes
      and 30 controls. The study group was divided into 2 subgroups: 23 patients with
      diabetic foot and 22 patients without diabetic complications. The concentration
      of VEGF-A, soluble VEGF receptor 2 (sVEGF-R2) and FGF-2 were measured in plasma
      samples. The number of circulating EPCs was determined in peripheral venous
      blood. The number of endothelial progenitor cells was measured with FACSCalibur
      flow cytometer using monoclonal antibodies directed against antigens specific for
      EPCs. RESULTS: In our study we observed significant higher levels of VEGF-A and
      FGF-2 and lower sVEGF-R2 concentration in patients with T2DM compared to healthy
      subjects. The conducted analysis showed decreased levels of VEGF-A and elevated
      levels of FGF-2 in patients with DM complicated DFS compared to diabetic patients
      without DFS. Increased circulating EPCs number was reported in patients with DFS,
      and the difference was almost statistically significant. CONCLUSIONS: The high
      concentration of VEGF-A and FGF-2, and a positive correlation between them
      indicate their participation in the process of angiogenesis in T2DM. Decreased
      sVEGF-R2 may result from inactivation of VEGF-A during complexes formation.

PMID- 25872464
TI  - Phenotypic and functional characterization of long-term cryopreserved human
      adipose-derived stem cells.
AB  - Cryopreservation represents an effective technique to maintain the functional
      properties of human adipose-derived stem cells (ASCs) and allows pooling of cells
      via long-term storage for clinical applications, e.g., cell-based therapies. It
      is crucial to reduce freezing injury during the cryopreservation process by
      loading the ASCs with the optimum concentration of suitable cryoprotective agents
      (CPAs). In this study, human ASCs were preserved for 3 months in different
      combinations of CPAs, including 1) 0.25 M trehalose; 2) 5% dimethylsulfoxide
      (DMSO); 3) 10% DMSO; 4) 5% DMSO + 20% fetal bovine serum (FBS); 5) 10% DMSO + 20%
      FBS; 6) 10% DMSO + 90% FBS. Interestingly, even with a reduction of DMSO to 5%
      and without FBS, cryopreserved ASCs maintained high cell viability comparable
      with standard cryomedium (10% DMSO + 90% FBS), with normal cell phenotype and
      proliferation rate. Cryopreserved ASCs also maintained their differentiation
      capability (e.g., to adipocytes, osteocytes and chondrocytes) and showed an
      enhanced expression level of stemness markers (e.g., NANOG, OCT-4, SOX-2 and REX
      1). Our findings suggest that 5% DMSO without FBS may be an ideal CPA for an
      efficient long-term cryopreservation of human ASCs. These results aid in
      establishing standardized xeno-free long-term cryopreservation of human ASCs for
      clinical applications. 

PMID- 25872465
TI  - Does laterally rotated flap design influence the short-term periodontal status of
      second molars and postoperative discomfort after partially impacted third molar
      surgery?
AB  - PURPOSE: To assess the influence of the surgical removal of partially impacted
      third molars (3Ms) and compare the effects of a 3-cornered laterally rotated flap
      (LRF) with primary closure (flap 1) and an envelope flap with secondary closure
      (flap 2) on the short-term periodontal status of the adjacent second molars
      (2Ms). We also assessed the postoperative complications after removal of the
      partially impacted 3M. MATERIALS AND METHODS: A split mouth, randomized clinical
      study was designed. The study sample included patients with bilateral partially
      impacted 3Ms. The primary predictor variable was the type of flap design (flaps 1
      and 2). The primary outcome variable was periodontal status (gingival recession
      [GR], probing depth [PD], plaque index [PI], and gingival index) of the 2Ms
      measured preoperatively and 90 days postoperatively. The secondary outcome
      variables were postoperative complications, including pain, facial swelling,
      alveolitis, and local wound infection. The other variables included gender,
      position of the 3Ms, and surgical difficulty. We performed descriptive,
      comparative, correlation, and multivariate analyses. RESULTS: The sample included
      28 patients aged 18 to 28 years. The GR, PD, and PI values with the flap 2 design
      were greater than those with the flap 1 design (P < .05). Facial swelling with
      the flap 1 design was significantly greater than with the flap 2 design on the
      second postoperative day (P < .05). The pain levels with the flap 1 design were
      significantly greater than those with the flap 2 design on the first and second
      postoperative days (P < .05). According to the multivariate regression analyses,
      flap design was closely related to the periodontal status of the 2Ms and
      postoperative discomfort. CONCLUSION: The results of the present clinical study
      have shown that the flap design in partially impacted 3M surgery considerably
      influences the early periodontal health of the 2Ms and postoperative discomfort.
      However, although the 3-cornered LRF design might cause more pain and swelling,
      it could be the method of choice for partially impacted 3M surgery because of the
      early periodontal healing.

PMID- 25872466
TI  - Advantages and limitations of Raman spectroscopy for molecular diagnostics: an
      update.
AB  - Over the last decade, Raman spectroscopy has gained more and more interest in
      research as well as in clinical laboratories. As a vibrational spectroscopy
      technique, it is complementary to the also well-established infrared
      spectroscopy. Through specific spectral patterns, substances can be identified
      and molecular changes can be observed with high specificity. Because of a high
      spatial resolution due to an excitation wavelength in the visible and near
      infrared range, Raman spectroscopy combined with microscopy is very powerful for
      imaging biological samples. Individual cells can be imaged on the subcellular
      level. In vivo tissue examinations are becoming increasingly important for
      clinical applications. In this review, we present currently ongoing research in
      different fields of medical diagnostics involving linear Raman spectroscopy and
      imaging. We give a wide overview over applications for the detection of
      atherosclerosis, cancer, inflammatory diseases and pharmacology, with a focus on
      developments over the past 5 years. Conclusions drawn from Raman spectroscopy are
      often validated by standard methods, for example, histopathology or PCR. The
      future potential of Raman spectroscopy and its limitations are discussed in
      consideration of other non-linear Raman techniques. 

PMID- 25872467
TI  - A general proof of consistency of heuristic classification for cognitive
      diagnosis models.
AB  - The Asymptotic Classification Theory of Cognitive Diagnosis (Chiu et al., 2009,
      Psychometrika, 74, 633-665) determined the conditions that cognitive diagnosis
      models must satisfy so that the correct assignment of examinees to proficiency
      classes is guaranteed when non-parametric classification methods are used. These
      conditions have only been proven for the Deterministic Input Noisy Output AND
      gate model. For other cognitive diagnosis models, no theoretical legitimization
      exists for using non-parametric classification techniques for assigning examinees
      to proficiency classes. The specific statistical properties of different
      cognitive diagnosis models require tailored proofs of the conditions of the
      Asymptotic Classification Theory of Cognitive Diagnosis for each individual model
      - a tedious undertaking in light of the numerous models presented in the
      literature. In this paper a different way is presented to address this task. The
      unified mathematical framework of general cognitive diagnosis models is used as a
      theoretical basis for a general proof that under mild regularity conditions any
      cognitive diagnosis model is covered by the Asymptotic Classification Theory of
      Cognitive Diagnosis.

PMID- 25872468
TI  - Catalyst-controlled reverse selectivity in C-C bond formation: NHC-Cu-catalyzed
      alpha-selective allylic alkylation with organolithium reagents.
AB  - An efficient and highly alpha-selective copper-catalyzed allylic alkylation of
      allylic halides with organolithium reagents is presented. The use of N
      heterocyclic carbenes as ligands is key to reverse the common gamma-selectivity
      of this transformation and gives rise to the corresponding linear products with
      high levels of regioselectivity. 

PMID- 25872469
TI  - Production of DUSP1 protein using the baculovirus insect cell expression system
      and its in vitro effects on cancer cells.
AB  - The aim of the present study was to produce the human dual specificity
      phosphatase 1 (DUSP1) protein with biological activity and to investigate its in
      vitro effects on cancer cells. DUSP1 protein was expressed in the baculovirus
      expression system and purified by Ni-affinity chromatography followed by dialysis
      in PBS. The purified protein was verified by SDS-PAGE and western blot analysis.
      Six cancer cell lines were then cultured in the presence of DUSP1 for various
      periods of time, and the phosphorylated extracellular signal-regulated kinase (p
      ERK) content in each cell line was subsequently determined by western blot
      analysis. Compared to the beta-actin level, the amount of p-ERK markedly
      decreased after 1 h, indicating that DUSP1 suppressed the expression of p-ERK in
      6 cancer cell lines examined. Human cervical cancer cells were also collected and
      counted following co-culture with DUSP1 to examine its effect on the growth rate
      of cancer cells. A baculovirus expression system for the production of DUSP1
      protein was successfully constructed. The p-ERK content was found to be
      significantly decreased when the cancer cell lines were exposed to DUSP1. The
      capability of binary fission was reduced when the cells were examined under a
      microscope. The proliferation of human cervical cancer cells was also inhibited
      by DUSP1.

PMID- 25872470
TI  - Solar-Light-Driven Renewable Butanol Separation by Core-Shell Ag@ZIF-8 Nanowires.
AB  - Core-shell Ag@ZIF-8 nanowires, where single Ag nanowires are coated with uniform
      zeolitic-imidazolate-framework-8 (ZIF-8) shells, successfully realize renewable
      adsorptive separation of low concentrations of butanol from an aqueous medium
      under solar light irradiation by taking advantage of the exceptional adsorption
      capability of the ZIF-8 shells toward butanol and the unique plasmonic
      photothermal effect of the Ag nanowire cores. Impressively, the high separation
      efficiency is maintained as almost unchanged, even after 10 adsorption/desorption
      cycles. 

PMID- 25872471
TI  - Effect of treatment and mammography detection on breast cancer survival over
      time: 1990-2007.
AB  - BACKGROUND: The extent to which improvements over time in breast cancer survival
      are related to earlier detection by mammography or to more effective treatments
      is not known. METHODS: At a comprehensive cancer care center, the authors
      conducted a retrospective cohort study of women ages 50 to 69 years who were
      diagnosed with invasive breast cancer (stages I through III) and were followed
      over 3 periods (1990-1994, 1995-1999, and 2000-2007). Data were abstracted from
      patient charts and included detection method, diagnosis, treatment, and follow-up
      for vital status in the institutional breast cancer registry (n = 2998). The
      method of detection was categorized as patient or physician detected or
      mammography detected. Cox proportional hazards models were used to estimate
      adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for 5-year
      disease-specific survival in relation to detection method and treatment factors,
      and differences in survival were analyzed using the Kaplan-Meier method. RESULTS:
      Fifty-eight percent of breast cancers were mammography detected, and 42% were
      patient or physician detected; 56% of tumors were stage I, 31% were stage II, and
      13% were stage III. The average length of follow-up was 10.71 years. The combined
      5-year disease-specific survival rate was 89% from 1990 to 1994, 94% from 1995 to
      1999, and 96% from 2000 to 2007 (P < .001). In an adjusted model, mammography
      detection (HR, 0.43; 95% CI, 0.27-0.70), hormone therapy (HR, 0.47; 95% CI, 0.30
      0.75), and taxane-containing chemotherapy (HR, 0.61; 95% CI, 0.37-0.99) were
      significantly associated with a decreased risk of disease-specific mortality.
      CONCLUSIONS: Better breast cancer survival over time was related to mammography
      detection, hormone therapy, and taxane-containing chemotherapy. Treatment
      improvements alone are not sufficient to explain the observed survival
      improvements over time.

PMID- 25872472
TI  - Determination of organophosphate esters in water samples by mixed-mode liquid
      chromatography and tandem mass spectrometry.
AB  - A simple and sensitive method for the determination of organophosphate esters in
      water samples by mixed-mode liquid chromatography with electrospray ionization
      tandem mass spectrometry coupled with solid-phase extraction is developed. Using
      seven alkyl phosphates, three chlorinated alkyl phosphates, and four aryl
      phosphates as the targets, the developed method was systematically evaluated on
      the basis of the influence of the solid-phase extraction cartridge, eluting
      solvent, sample-loading volume, mobile phase condition, and the separation of
      reversed-phase chromatography and mixed-mode liquid chromatography. Under the
      optimal conditions, these organophosphate esters can be extracted by ENVI-18
      cartridge, eluted by 6 mL of 25% dichloromethane in acetonitrile, and then
      qualified and quantified by mixed-mode liquid chromatography with tandem mass
      spectrometry in the multiple reaction-monitoring mode. The application of mixed
      mode liquid chromatography endows the separation with reasonable retention for
      both hydrophilic and hydrophobic organophosphate esters regardless of their
      polarity, which is hardly achieved by reversed-phase chromatography. Good
      linearity (from 0.9877 to 0.9969), low quantification limits (1-35 ng/L after
      extraction of 100 mL of river water), and acceptable recovery rates (58.6-116.2%,
      with the relative standard deviation <18.0%) were obtained. Finally, the
      established method was used for analyzing surface water samples, and the good
      applicability of this method was demonstrated. 

PMID- 25872473
TI  - Enhanced magnetic properties in antiferromagnetic-core/ferrimagnetic-shell
      nanoparticles.
AB  - Bi-magnetic core/shell nanoparticles are gaining increasing interest due to their
      foreseen applications. Inverse antiferromagnetic(AFM)/ferrimagnetic(FiM)
      core/shell nanoparticles are particularly appealing since they may overcome some
      of the limitations of conventional FiM/AFM systems. However, virtually no
      simulations exist on this type of morphology. Here we present systematic
      Metropolis Monte Carlo simulations of the exchange bias properties of such
      nanoparticles. The coercivity, HC, and loop shift, Hex, present a non-monotonic
      dependence with the core diameter and the shell thickness, in excellent agreement
      with the available experimental data. Additionally, we demonstrate novel
      unconventional behavior in FiM/AFM particles. Namely, while HC and Hex decrease
      upon increasing FiM thickness for small AFM cores (as expected), they show the
      opposite trend for large cores. This presents a counterintuitive FiM size
      dependence for large AFM cores that is attributed to the competition between core
      and shell contributions, which expands over a wider range of core diameters
      leading to non-vanishing Hex even for very large cores. Moreover, the results
      also hint different possible ways to enhance the experimental performance of
      inverse core/shell nanoparticles for diverse applications. 

PMID- 25872474
TI  - Photoelectrochemical reaction for the efficient production of hydrogen and high
      value-added oxidation reagents.
AB  - A porous and thick photoelectrode of WO3 in the monoclinic phase was prepared to
      realize the recovery of H2 and high-value-added oxidation reagents with efficient
      solar energy conversion. The WO3 photoelectrode enabled the efficient production
      and accumulation of O2 , S2 O8 (2-) , Ce(4+) , and IO4 (-) as oxidation products.
      Most notably, S2 O8 (2-) , which possesses the highest oxidizability among all
      the peroxides, was generated with high applied bias photon-to-current efficiency
      (2.2 %) and faraday efficiency (~100 %) upon irradiation from the back side of
      the photoelectrode. The design of a tandem photoelectrode system combining a dye
      sensitized solar cell (DSSC) was also challenged for the realization of this
      photoelectrode system without external bias. A high solar energy conversion
      efficiency (5.2 %) was achieved in the tandem system comprising the WO3
      photoelectrode connected to two DSSCs with a near-IR-utilizing dye in series for
      the production of H2 and S2 O8 (2-) . 

PMID- 25872476
TI  - LSm1 binds to the Dengue virus RNA 3' UTR and is a positive regulator of Dengue
      virus replication.
AB  - Dengue virus (DENV) is a mosquito-transmitted flavivirus that can cause severe
      disease in humans. The DENV positive strand RNA genome contains 5' and 3'
      untranslated regions (UTRs) that have been shown to be required for virus
      replication and interaction with host cell proteins. In the present study LSm1
      was identified as a host cellular protein involved in DENV RNA replication. By
      using two independent methodologies, we demonstrated a critical interaction
      between LSm1 and the 3' UTR of DENV. Furthermore, the confocal immunofluorescence
      analysis showed that the interaction between LSm1 and viral RNA is located in P
      body around nucleoli in the cytoplasm. LSm1 knockdown by siRNA specifically
      reduced the levels of viral RNA in DENV-infected cells and infectious DENV
      particles in the supernatant. These results provide evidence that LSm1 binding to
      the DENV RNA 3' UTR positively regulates DENV RNA replication.

PMID- 25872477
TI  - A Novel Probe as Surface Glycan Marker of Pluripotent Stem Cells: Research
      Outcomes and Application to Regenerative Medicine.
AB  - Human pluripotent stem cells (hPSCs), represented by embryonic stem (hESCs) and
      induced pluripotent stem cells (hiPSCs), are attracting increasing attention in
      various research fields. However, their application in a clinical scenario must
      overcome an important hurdle given that these cells are potentially tumorigenic.
      This inherent problem becomes more significant as the number of transplanted
      cells becomes larger. In this Progress Report, recent findings concerning a novel
      glycan marker for hPSCs are described, as well as attempts made in relation to
      its practical application to regenerative medicine. In line with current thinking
      in the glycoscience field, it is assumed that cellular glycomes are closely
      related to cell functions. Based on this premise, hESCs and hiPSCs are analyzed
      by an advanced glycan profiling technology--the high-density lectin microarray.
      It is found that all human iPSCs derived from different tissular origins show
      essentially the same glycan profiles, which are typified by several
      characteristic structural features. In addition, a recombinant lectin probe,
      rBC2LCN, which shows rigorous specificity to H type 1 and 3 glycan structures, is
      found to serve as an excellent probe for hPSCs.

PMID- 25872475
TI  - Proteome mapping of epidermal growth factor induced hepatocellular carcinomas
      identifies novel cell metabolism targets and mitogen activated protein kinase
      signalling events.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is on the rise and the sixth most
      common cancer worldwide. To combat HCC effectively research is directed towards
      its early detection and the development of targeted therapies. Given the fact
      that epidermal growth factor (EGF) is an important mitogen for hepatocytes we
      searched for disease regulated proteins to improve an understanding of the
      molecular pathogenesis of EGF induced HCC. Disease regulated proteins were
      studied by 2DE MALDI-TOF/TOF and a transcriptomic approach, by
      immunohistochemistry and advanced bioinformatics. RESULTS: Mapping of EGF induced
      liver cancer in a transgenic mouse model identified n = 96 (p < 0.05)
      significantly regulated proteins of which n = 54 were tumour-specific. To unravel
      molecular circuits linked to aberrant EGFR signalling diverse computational
      approaches were employed and this defined n = 7 key nodes using n = 82 disease
      regulated proteins for network construction. STRING analysis revealed protein
      protein interactions of > 70% disease regulated proteins with individual proteins
      being validated by immunohistochemistry. The disease regulated network proteins
      were mapped to distinct pathways and bioinformatics provided novel insight into
      molecular circuits associated with significant changes in either glycolysis and
      gluconeogenesis, argine and proline metabolism, protein processing in endoplasmic
      reticulum, Hif- and MAPK signalling, lipoprotein metabolism, platelet activation
      and hemostatic control as a result of aberrant EGF signalling. The biological
      significance of the findings was corroborated with gene expression data derived
      from tumour tissues to evntually define a rationale by which tumours embark on
      intriguing changes in metabolism that is of utility for an understanding of
      tumour growth. Moreover, among the EGF tumour specific proteins n = 11 were
      likewise uniquely expressed in human HCC and for n = 49 proteins regulation in
      human HCC was confirmed using the publically available Human Protein Atlas
      depository, therefore demonstrating clinical significance. CONCLUSION: Novel
      insight into the molecular pathogenesis of EGF induced liver cancer was obtained
      and among the 37 newly identified proteins several are likely candidates for the
      development of molecularly targeted therapies and include the nucleoside
      diphosphate kinase A, bifunctional ATP-dependent dihydroyacetone kinase and
      phosphatidylethanolamine-binding protein1, the latter being an inhibitor of the
      Raf-1 kinase.

PMID- 25872478
TI  - Chloroquine exerts neuroprotection following traumatic brain injury via
      suppression of inflammation and neuronal autophagic death.
AB  - The antimalarial drug, chloroquine (CQ), has been reported as an autophagy
      inhibitor in a variety of disorders, including Alzheimer's disease and brain
      ischemia. To the best of our knowledge, no studies to date have examined the
      potential for CQ to provide neuroprotection in animal models of traumatic brain
      injury (TBI). The aim of this study was to investigate the neuroprotective
      actions of CQ in TBI and to determine the mechanisms underlying this effect. Rats
      were immediately subjected to a diffuse cortical impact injury caused by a
      modified weight-drop device and divided randomly into three groups: sham
      operated, CQ treatment and vehicle. The CQ treatment group was administered CQ
      (intraperitoneally, 3 mg/kg body weight) immediately following the induction of
      injury. The co-localization of neuron-specific nuclear protein (NeuN) and
      microtubule-associated protein 1 light chain 3 (LC3), was followed by
      immunofluorescent staining. The expression of LC3 and inflammatory cytokines was
      identified by western blot analysis. Wet-dry weight method was utilized to
      evaluate TBI-induced brain edema. Motor function was evaluated using the
      Neurological Severity Score (NSS) scale and the Morris water maze was employed to
      assess spatial learning ability. This study demonstrated that the administration
      of CQ attenuates TBI-induced cerebral edema, and the associated motor and
      cognitive functional deficits that occur post-injury. Following the induction of
      cerebral trauma, CQ treatment significantly suppressed neuronal autophagy and
      reduced expression levels of the inflammatory cytokines, interleukin-1beta (IL
      1beta) and tumor necrosis factor-alpha (TNF-alpha), in the rat hippocampus. Our
      results have provided in vivo evidence that CQ may exert neuroprotective effects
      following TBI, in attenuating brain edema and improving neurological functioning,
      by reducing the damaging consequences of neuronal autophagy and cerebral
      inflammation.

PMID- 25872479
TI  - Fangchinoline targets PI3K and suppresses PI3K/AKT signaling pathway in SGC7901
      cells.
AB  - Fangchinoline, an important compound in Stephania tetrandra S. Moore, as a novel
      antitumor agent, has been implicated in several types of cancers cells except
      gastric cancer. To investigate whether fangchinoline affects gastric cancer
      cells, we detected the signaling pathway by which fangchinoline plays a role in
      different human gastric cancer cells lines. We found that fangchinoline
      effectively suppressed proliferation and invasion of SGC7901 cell lines, but not
      MKN45 cell lines by inhibiting the expression of PI3K and its downstream pathway.
      All of the Akt/MMP2/MMP9 pathway, Akt/Bad pathway, and Akt/Gsk3beta/CDK2 pathway
      could be inhibited by fangchinoline through inhibition of PI3K. Taken together,
      these results suggest that fangchinoline targets PI3K in tumor cells that express
      PI3K abundantly and inhibits the growth and invasive ability of the tumor cells. 

PMID- 25872480
TI  - Immunization with Ty21a live oral typhoid vaccine elicits crossreactive
      multifunctional CD8+ T-cell responses against Salmonella enterica serovar Typhi,
      S. Paratyphi A, and S. Paratyphi B in humans.
AB  - Previously we have extensively characterized Salmonella enterica serovar Typhi
      (S. Typhi)-specific cell-mediated immune (CMI) responses in volunteers orally
      immunized with the licensed Ty21a typhoid vaccine. In this study we measured
      Salmonella-specific multifunctional (MF) CD8+ T-cell responses to further
      investigate whether Ty21a elicits crossreactive CMI against S. Paratyphi A and S.
      Paratyphi B that also cause enteric fever. Ty21a-elicited crossreactive CMI
      responses against all three Salmonella serotypes were predominantly observed in
      CD8+ T effector/memory (T(EM)) and, to a lesser extent, in CD8+CD45RA+ T(EM)
      (T(EMRA)) subsets. These CD8+ T-cell responses were largely mediated by MF cells
      coproducing interferon-gamma and macrophage inflammatory protein-1beta and
      expressing CD107a with or without tumor necrosis factor-alpha. Significant
      proportions of Salmonella-specific MF cells expressed the gut-homing molecule
      integrin alpha4beta7. In most subjects, similar MF responses were observed to S.
      Typhi and S. Paratyphi B, but not to S. Paratyphi A. These results suggest that
      Ty21a elicits MF CMI responses against Salmonella that could be critical in
      clearing the infection. Moreover, because S. Paratyphi A is a major public
      concern and Ty21a was shown in field studies not to afford cross-protection to S.
      Paratyphi A, these results will be important in developing a S. Typhi/S.
      Paratyphi A bivalent vaccine against enteric fevers.

PMID- 25872481
TI  - New developments in goblet cell mucus secretion and function.
AB  - Goblet cells and their main secretory product, mucus, have long been poorly
      appreciated; however, recent discoveries have changed this and placed these cells
      at the center stage of our understanding of mucosal biology and the immunology of
      the intestinal tract. The mucus system differs substantially between the small
      and large intestine, although it is built around MUC2 mucin polymers in both
      cases. Furthermore, that goblet cells and the regulation of their secretion also
      differ between these two parts of the intestine is of fundamental importance for
      a better understanding of mucosal immunology. There are several types of goblet
      cell that can be delineated based on their location and function. The surface
      colonic goblet cells secrete continuously to maintain the inner mucus layer,
      whereas goblet cells of the colonic and small intestinal crypts secrete upon
      stimulation, for example, after endocytosis or in response to acetyl choline.
      However, despite much progress in recent years, our understanding of goblet cell
      function and regulation is still in its infancy. 

PMID- 25872482
TI  - Identification of preferential CD4+ T-cell targets for HIV infection in the
      cervix.
AB  - A better understanding of the cellular targets of HIV infection in the female
      genital tract may inform HIV prevention efforts. Proposed correlates of cellular
      susceptibility include the HIV co-receptor CCR5, peripheral homing integrins, and
      immune activation. We used a CCR5-tropic pseudovirus to quantify HIV entry into
      unstimulated endocervical CD4(+) T cells collected by cytobrush. Virus entry was
      threefold higher into cervix-derived CD4(+) T cells than blood, but was strongly
      correlated between these two compartments. Cervix-derived CD4(+) T cells
      expressing CD69, alpha(4)beta(7), or alpha(4)beta(1) were preferential HIV
      targets; this enhanced susceptibility was strongly correlated with increased CCR5
      expression in alpha(4)beta(7)(+) and CD69(+) CD4(+) T cells, and to a lesser
      extent in alpha(4)beta(1)(+) CD4(+) T cells. Direct binding of gp140 to integrins
      was not observed, integrin inhibitors had no effect on virus entry, and
      pseudotypes with an env that preferentially binds alpha(4)beta(7) still
      demonstrated enhanced entry into alpha(4)beta(1)(+) cells. In summary, a rapid
      and sensitive HIV entry assay demonstrated enhanced susceptibility of activated
      endocervical CD4(+) T cells, and those expressing alpha(4)beta(7) or
      alpha(4)beta(1). This may relate to increased CCR5 expression by these cell
      subsets, but did not appear to be due to direct interaction of alpha(4)beta(7) or
      alpha(4)beta(1) with HIV envelope.

PMID- 25872484
TI  - miR-203 inhibits arecoline-induced epithelial-mesenchymal transition by
      regulating secreted frizzled-related protein 4 and transmembrane-4 L six family
      member 1 in oral submucous fibrosis.
AB  - Oral submucous fibrosis (OSF) is a potentially malignant disease predominantly
      found in Asian people. The areca nut has been implicated in this disease.
      Arecoline, one of the areca alkaloids, induces epithelial-mesenchymal transition
      (EMT)-related factors in primary human buccal mucosal fibroblasts. Yet, the
      mechanisms of the underlying arecoline-induced EMT in OSF remain unknown. In the
      present study, we aimed to investigate the role of microRNAs (miRNAs) in
      arecoline-induced EMT in HaCaT cells. We found that miR-203 was significantly
      downregulated in OSF tissues compared to that in normal buccal mucosa tissues,
      and that miR-203 negatively regulated secreted frizzled-related protein 4 (SFRP4)
      and positively regulated transmembrane-4 L six family member 1 (TM4SF1). We
      observed that upregulation of miR-203 significantly decreased the cell
      proliferation of HaCaT cells, and significantly upregulated the expression of
      cytokeratin 19 (CK19) and E-cadherin proteins, whereas it significantly
      downregulated the expression of N-cadherin and vimentin compared to these levels
      in the vehicle control cells. Thus, we provide evidence to illustrate that miR
      203 plays a role in the pathogenesis of OSF, which may be a target for OSF
      management.

PMID- 25872483
TI  - Novel chimpanzee adenovirus-vectored respiratory mucosal tuberculosis vaccine:
      overcoming local anti-human adenovirus immunity for potent TB protection.
AB  - Pulmonary tuberculosis (TB) remains to be a major global health problem despite
      many decades of parenteral use of Bacillus Calmette-Guerin (BCG) vaccine.
      Developing safe and effective respiratory mucosal TB vaccines represents a unique
      challenge. Over the past decade or so, the human serotype 5 adenovirus (AdHu5)
      based TB vaccine has emerged as one of the most promising candidates based on a
      plethora of preclinical and early clinical studies. However, anti-AdHu5 immunity
      widely present in the lung of humans poses a serious gap and limitation to its
      real-world applications. In this study we have developed a novel chimpanzee
      adenovirus 68 (AdCh68)-vectored TB vaccine amenable to the respiratory route of
      vaccination. We have evaluated AdCh68-based TB vaccine for its safety, T-cell
      immunogenicity, and protective efficacy in relevant animal models of human
      pulmonary TB with or without parenteral BCG priming. We have also compared AdCh68
      based TB vaccine with its AdHu5 counterpart in both naive animals and those with
      preexisting anti-AdHu5 immunity in the lung. We provide compelling evidence that
      AdCh68-based TB vaccine is not only safe when delivered to the respiratory tract
      but, importantly, is also superior to its AdHu5 counterpart in induction of T
      cell responses and immune protection, and limiting lung immunopathology in the
      presence of preexisting anti-AdHu5 immunity in the lung. Our findings thus
      suggest AdCh68-based TB vaccine to be an ideal candidate for respiratory mucosal
      immunization, endorsing its further clinical development in humans. 

PMID- 25872485
TI  - Long-term survival in patients with metastatic gastric and gastroesophageal
      cancer treated with surgery.
AB  - BACKGROUND: The purpose of this study was to determine the survival of patients
      with metastatic gastric cancer treated with surgery. METHODS: We reviewed the
      medical records of 7,404 patients with gastric or gastroesophageal cancer seen
      from January 1995 to August 2012 at MD Anderson Cancer Center and identified
      patients with stage IV disease treated with surgery. Kaplan-Meier curves were
      created to compare overall survival (OS) between groups. RESULTS: Of the 82
      patients who met inclusion criteria, sites of metastatic disease included
      peritoneum (N = 34, 42%), positive cytology only (N = 17, 21%), distant lymph
      nodes (N = 12, 15%), and distant organs (N = 19, 23%). The median time from
      initial cancer diagnosis to surgery for metastatic disease was 10 months (range,
      0-70). Surgery included exploratory surgery only (N = 16, 20%), primary tumor
      resection with or without resection of distant disease (N = 50, 61%), and distant
      disease resection only (N = 16, 20%). Median follow-up for living patients was 3
      years (range, 0.1-14). Median survival for all patients was 1.5 years (range, 0.1
      14). Five year OS for patients with peritoneal metastases, positive cytology
      only, distant lymph nodes, and distant organ involvement was 13, 42, 20, and 34%,
      respectively. CONCLUSIONS: Surgery in the setting of metastatic disease is an
      uncommon clinical scenario and has a considerable risk of exploration without
      resection, although long-term survival is possible.

PMID- 25872486
TI  - Cluster evolution during the early stages of heating explosives and its
      relationship to sensitivity: a comparative study of TATB, beta-HMX and PETN by
      molecular reactive force field simulations.
AB  - Clustering is experimentally and theoretically verified during the complicated
      processes involved in heating high explosives, and has been thought to influence
      their detonation properties. However, a detailed description of the clustering
      that occurs has not been fully elucidated. We used molecular dynamic simulations
      with an improved reactive force field, ReaxFF_lg, to carry out a comparative
      study of cluster evolution during the early stages of heating for three
      representative explosives: 1,3,5-triamino-2,4,6-trinitrobenzene (TATB), beta
      1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) and pentaerythritol tetranitrate
      (PETN). These representatives vary greatly in their oxygen balance (OB),
      molecular structure, stability and experimental sensitivity. We found that when
      heated, TATB, HMX and PETN differ in the size, amount, proportion and lifetime of
      their clusters. We also found that the clustering tendency of explosives
      decreases as their OB becomes less negative. We propose that the relationship
      between OB and clustering can be attributed to the role of clustering in
      detonation. That is, clusters can form more readily in a high explosive with a
      more negative OB, which retard its energy release, secondary decomposition,
      further decomposition to final small molecule products and widen its detonation
      reaction zone. Moreover, we found that the carbon content of the clusters
      increases during clustering, in accordance with the observed soot, which is
      mainly composed of carbon as the final product of detonation or deflagration. 

PMID- 25872488
TI  - Live long and prosper: the enterprise of understanding diseased epithelium.
AB  - The epithelium is a particularly complicated and dynamic tissue, and
      dysregulation of epithelial structure and function is a hallmark of several lung
      diseases. Motivated by the life and recent passing of Leonard Nimoy, we highlight
      several recent studies that explore the nuanced relationship between the
      epithelium and disease progression. Specifically, we focus on recent innovative
      and integrative approaches that shed new light on epithelial wounding, healing,
      and development.

PMID- 25872487
TI  - Comparing high-resolution microscopy techniques for potential intraoperative use
      in guiding low-grade glioma resections.
AB  - BACKGROUND AND OBJECTIVES: Fluorescence image-guided surgery (FIGS), with
      contrast provided by 5-ALA-induced PpIX, has been shown to enable a higher extent
      of resection of high-grade gliomas. However, conventional FIGS with low-power
      microscopy lacks the sensitivity to aid in low-grade glioma (LGG) resection
      because PpIX signal is weak and sparse in such tissues. Intraoperative high
      resolution microscopy of PpIX fluorescence has been proposed as a method to guide
      LGG resection, where sub-cellular resolution allows for the visualization of
      sparse and punctate mitochondrial PpIX production in tumor cells. Here, we assess
      the performance of three potentially portable high-resolution microscopy
      techniques that may be used for the intraoperative imaging of human LGG tissue
      samples with PpIX contrast: high-resolution fiber-optic microscopy (HRFM), high
      resolution wide-field microscopy (WFM), and dual-axis confocal (DAC) microscopy.
      MATERIALS AND METHODS: Thick unsectioned human LGG tissue samples (n = 7) with 5
      ALA-induced PpIX contrast were imaged using three imaging techniques (HRFM, WFM,
      DAC). The average signal-to-background ratio (SBR) was then calculated for each
      imaging modality (5 images per tissue, per modality). RESULTS: HRFM provides the
      ease of use and portability of a flexible fiber bundle, and is simple and
      inexpensive to build. However, in most cases (6/7), HRFM is not capable of
      detecting PpIX signal from LGGs due to high autofluorescence, generated by the
      fiber bundle under laser illumination at 405 nm, which overwhelms the PpIX signal
      and impedes its visualization. WFM is a camera-based method possessing high
      lateral resolution but poor axial resolution, resulting in sub-optimal image
      contrast. CONCLUSIONS: Consistent successful detection of PpIX signal throughout
      our human LGG tissue samples (n = 7), with an acceptable image contrast (SBR >2),
      was only achieved using DAC microscopy, which offers superior image resolution
      and contrast that is comparable to histology, but requires a laser-scanning
      mechanism to achieve optical sectioning.

PMID- 25872489
TI  - G-protein-coupled receptor 30-mediated antiapoptotic effect of estrogen on spinal
      motor neurons following injury and its underlying mechanisms.
AB  - Spinal cord injury (SCI) may result in severe dysfunction of motor neurons. G
      protein-coupled receptor 30 (GPR30) expression in the motor neurons of the
      ventral horn of the spinal cord mediates neuroprotection through estrogen
      signaling. The present study explored the antiapoptotic effect of estrogen,
      mediated by GPR30 following SCI, and the mechanisms underlying this effect.
      Spinal motor neurons from rats were cultured in vitro in order to establish cell
      models of oxygen and glucose deprivation (OGD). The effects of estrogen, the
      estrogen agonist, G1, and the estrogen inhibitor, G15, on motor neurons were
      observed using MTT assays. The effects of E2, G1 and G15 on spinal motor neuron
      apoptosis following OGD, were detected using flow cytometry. The role of the
      phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) inhibitor, LY294002,
      was also determined using flow cytometry. Rat SCI models were established. E2, G1
      and E2+LY294002 were administered in vivo. Motor function was scored at 3, 7, 14,
      21 and 28 d following injury, using Basso-Beattie-Bresnahan (BBB) standards. Cell
      activity in the estrogen and G1 groups was higher than that in the solvent group,
      whereas cell activity in the E2+G15 group was lower than that in the E2 group
      (P<0.05). Following OGD, the proportion of apoptotic cells significantly
      increased (P<0.05). The proportion in the estrogen group was significantly lower
      than that in the solvent group, whereas the proportion of apoptotic cells in the
      E2+G15 and E2+LY294002 groups was higher than that in the E2 group (P<0.05).
      Treatment with E2 and G1 led to upregulation of P-Akt expression in normal cells
      and post-OGD cells. The BBB scores of rats in the E2 and G1 groups were higher
      than those in the placebo group (P<0.05). The BBB scores of the E2+LY294002 group
      were lower than those of the E2 group (P<0.05). Estrogen thus appears to exert a
      protective effect on spinal motor neurons following OGD, via GPR30. The PI3K/Akt
      pathway may be one of those involved in the estrogen-related antiapoptotic
      effects mediated by GPR30.

PMID- 25872490
TI  - A ratiometric fluorescence sensor for Fe(3+) based on FRET and PET processes.
AB  - A rhodamine/coumarin-based ratiometric fluorescent Fe(3+) sensor has been
      designed and synthesized. The sensor exhibits a good response to Fe(3+) ions with
      high sensitivity, selectivity and a large shift in the emission spectra (>100
      nm), which shows Fe(3+) -induced FRET OFF-ON and PET ON-OFF behavior.

PMID- 25872491
TI  - Preoperative Cerebrovascular Evaluation in Patients With Infective Endocarditis.
AB  - Approximately 12% to 40% of infective endocarditis patients experience
      cerebrovascular complications. One of the major clinical challenges in
      cerebrovascular medicine is management of infective endocarditis patients with
      cerebrovascular complications who require valve operations. Cerebrovascular
      specialists are often summoned to address appropriate preoperative brain imaging,
      timing of surgery, and estimation of the risk of perioperative cerebral
      embolization and hemorrhage. This article addresses these issues based on the
      available evidence. 

PMID- 25872492
TI  - A Palladium(II)-Catalyzed C-H Activation Cascade Sequence for Polyheterocycle
      Formation.
AB  - Polyheterocycles are found in many natural products and are useful moieties in
      functional materials and drug design. As part of a program towards the synthesis
      of Stemona alkaloids, a novel palladium(II)-catalyzed C-H activation strategy for
      the construction of such systems has been developed. Starting from simple 1,3
      dienyl-substituted heterocycles, a large range of polycyclic systems containing
      pyrrole, indole, furan and thiophene moieties can be synthesized in a single
      step.

PMID- 25872493
TI  - Surface modification of nano-silica on the ligament advanced reinforcement system
      for accelerated bone formation: primary human osteoblasts testing in vitro and
      animal testing in vivo.
AB  - The Ligament Advanced Reinforcement System (LARS) has been considered as a
      promising graft for ligament reconstruction. To improve its biocompatibility and
      effectiveness on new bone formation, we modified the surface of a polyethylene
      terephthalate (PET) ligament with nanoscale silica using atom transfer radical
      polymerization (ATRP) and silica polymerization. The modified ligament is tested
      by both in vitro and in vivo experiments. Human osteoblast testing in vitro
      exhibits an ~21% higher value in cell viability for silica-modified grafts
      compared with original grafts. Animal testing in vivo shows that there is new
      formed bone in the case of a nanoscale silica-coated ligament. These results
      demonstrate that our approach for nanoscale silica surface modification on LARS
      could be potentially applied for ligament reconstruction. 

PMID- 25872494
TI  - miR-424/322 is downregulated in the semen of patients with severe DNA damage and
      may regulate sperm DNA damage.
AB  - Sperm DNA integrity is an essential factor for accurate transmission of genetic
      information. Human sperm DNA damage is a common cause of male infertility but the
      exact mechanism remains poorly understood. Considering the vital role of microRNA
      (miRNA) in multiple pathophysiological processes, we hypothesised that testicular
      miRNA is involved in sperm DNA damage during spermatogenesis. Infertile patients
      with high sperm DNA fragment index (DFI; n=94) were selected from 1090 infertile
      men and a total of 18 testis-specific seminal miRNAs previously identified from
      human seminal plasma were chosen and tested. miR-29c and miR-424 were
      downregulated in men with high DFI. The inhibition of these two miRNAs in mice
      confirmed the role of miR-424 (murine homologue miR-322) in sperm DNA damage
      during spermatogenesis; by contrast, miR-29c exhibited a negative result. Thus,
      miR-424/322 is involved in sperm DNA damage. Furthermore, the dysregulation of
      this miRNA can induce DNA double-strand breaks during spermatogenesis.

PMID- 25872495
TI  - Towards an ab initio description of the optical spectra of light-harvesting
      antennae: application to the CP29 complex of photosystem II.
AB  - Light-harvesting pigment-protein complexes (PPC) represent the fundamental units
      through which the photosynthetic organisms absorb sunlight and funnel the energy
      to the reaction centre for carrying out the primary energy conversion reactions
      of photosynthesis. Here we apply a multiscale computational strategy to a
      specific PPC present in the photosystem II of plants and algae (CP29) to
      investigate in what detail should the environment effects due to protein and
      membrane/solvent be included for an accurate description of optical spectra. We
      find that a refinement of the crystal structure is needed before any meaningful
      quantum chemical calculations of pigment transition energies can be performed.
      For this purpose we apply classical molecular dynamics simulations of the PPC
      within its natural environment and we perform ab initio computations of the
      exciton Hamiltonian of the complex, including the environment either implicitly
      by the polarizable continuum model (PCM) or explicitly using the polarizable
      QM/MM methodology (MMPol). However, PCM essentially leads to an unspecific
      redshift of all transition energies, and MMPol is able to reveal site-specific
      changes in the optical properties of the pigments. Based on the latter and the
      excitonic couplings obtained within a polarizable QM/MM methodology, optical
      spectra are calculated, which are in good qualitative agreement with experimental
      data. A weakness of the approach is however found in the overestimation of the
      fluctuations of the excitonic parameters of the pigments along the MD trajectory.
      An explanation for such a finding in terms of the limits of the force fields
      commonly used for protein cofactors is presented and discussed. 

PMID- 25872496
TI  - Managing superutilizers--staying patient centered is the solution.

PMID- 25872497
TI  - Strategy for Internal Labeling of Large RNAs with Minimal Perturbation by Using
      Fluorescent PNA.
AB  - Fluorescence techniques for the investigation of biomolecules and their folding
      pathways require an efficient labeling strategy. A common method to internally
      label large RNAs involves the introduction of long loops for hybridization of
      fluorophore-carrying DNA strands. Such loops often disturb the structure, and
      thus the functionality, of the RNA. Here we show, in a proof of concept study
      with a >600 nucleotide group II intron ribozyme, that the usage of the nucleic
      acid analogue peptide nucleic acid (PNA) is more efficient in several aspects,
      minimizing the required structural modifications of the RNA. We demonstrate by
      various methods, including smFRET, that much smaller concentrations and shorter
      PNAs can be applied, compared to DNA, for rapid and specific internal RNA
      labeling. The folding pathway and catalytic activity of this large ribozyme is
      only minimally affected by the PNA, but the background signal is significantly
      reduced. 

PMID- 25872498
TI  - Organization and Detailed Parcellation of Human Hippocampal Head and Body Regions
      Based on a Combined Analysis of Cyto- and Chemoarchitecture.
AB  - The hippocampal formation (HF) is one of the hottest regions in neuroscience
      because it is critical to learning, memory, and cognition, while being vulnerable
      to many neurological and mental disorders. With increasing high-resolution
      imaging techniques, many scientists have started to use distinct landmarks along
      the anterior-posterior axis of HF to allow segmentation into individual subfields
      in order to identify specific functions in both normal and diseased conditions.
      These studies urgently call for more reliable and accurate segmentation of the HF
      subfields DG, CA3, CA2, CA1, prosubiculum, subiculum, presubiculum, and
      parasubiculum. Unfortunately, very limited data are available on detailed
      parcellation of the HF subfields, especially in the complex, curved hippocampal
      head region. In this study we revealed detailed organization and parcellation of
      all subfields of the hippocampal head and body regions on the base of a combined
      analysis of multiple cyto- and chemoarchitectural stains and dense sequential
      section sampling. We also correlated these subfields to macro-anatomical
      landmarks, which are visible on magnetic resonance imaging (MRI) scans.
      Furthermore, we created three versions of the detailed anatomic atlas for the
      hippocampal head region to account for brains with four, three, or two
      hippocampal digitations. These results will provide a fundamental basis for
      understanding the organization, parcellation, and anterior-posterior difference
      of human HF, facilitating accurate segmentation and measurement of HF subfields
      in the human brain on MRI scans.

PMID- 25872500
TI  - Physical ACtivity facilitation for Elders (PACE): study protocol for a randomised
      controlled trial.
AB  - BACKGROUND: As people live longer, their risk of disability increases. Disability
      affects quality of life and increases health and social care costs. Preventing or
      delaying disability is therefore an important objective, and identifying an
      effective intervention could improve the lives of many older people.
      Observational and interventional evidence suggests that physical activity may
      reduce the risk of age-related disability, as assessed by physical performance
      measures. However it is unclear what approach is the most cost-effective
      intervention in changing long-term physical activity behaviour in older adults. A
      new theory-driven behavioural intervention has been developed, with the aim of
      increasing physical activity in the everyday lives of older adults at risk of
      disability. This pilot study tests the feasibility and acceptability of
      delivering this intervention to older adults. METHODS/DESIGN: A randomised
      controlled trial (RCT) design will be used in the pilot study. Sixty patients
      aged 65 years and older will be recruited from primary care practices. Patients
      will be eligible to participate if they are inactive, not disabled at baseline,
      are at risk of developing disability in the future (Short Physical Performance
      Battery score <10/12), and have no contraindications to physical activity.
      Following baseline measures, participants will be randomised in a 2:1 ratio to
      the intervention or to a control arm and all participants will be followed-up
      after 6 months. Those randomised to the intervention arm will receive sessions
      with a trained Physical Activity Facilitator, delivering an intervention based on
      self-determination theory. Control participants receive a booklet on healthy
      ageing. The main outcomes of interest are recruitment, adherence, retention and
      acceptability. Data will also be collected on: self-report and accelerometer
      recorded physical activity; physical performance; depression; wellbeing;
      cognitive function; social support; quality of life, healthcare use, and
      attitudes to physical activity. A mixed-methods process evaluation will run
      alongside the RCT. DISCUSSION: The intervention, if effective, has the potential
      to reduce disability and improve quality of life in older adults. Before
      proceeding to a full-scale trial a pilot trial is necessary to ensure
      intervention feasibility and acceptability, and that the intervention shows
      evidence of promise. TRIAL REGISTRATION: Current Controlled Trials ISRCTN80470273
      . Registered 25 October 2013.

PMID- 25872501
TI  - Evaluation of a point-of-care tuberculosis test-and-treat algorithm on early
      mortality in people with HIV accessing antiretroviral therapy (TB Fast Track
      study): study protocol for a cluster randomised controlled trial.
AB  - BACKGROUND: Early mortality for HIV-positive people starting antiretroviral
      therapy (ART) remains high in resource-limited settings, with tuberculosis the
      most important cause. Existing rapid diagnostic tests for tuberculosis lack
      sensitivity among HIV-positive people, and consequently, tuberculosis treatment
      is either delayed or started empirically (without bacteriological confirmation).
      We developed a management algorithm for ambulatory HIV-positive people, based on
      body mass index and point-of-care tests for haemoglobin and urine
      lipoarabinomannan (LAM), to identify those at high risk of tuberculosis and
      mortality. We designed a clinical trial to test whether implementation of this
      algorithm reduces six-month mortality among HIV-positive people with advanced
      immunosuppression. METHODS/DESIGN: The TB Fast Track study is an open, pragmatic,
      cluster randomised superiority trial, with 24 primary health clinics randomised
      to implement the intervention or standard of care. Adults (aged >=18 years) with
      a CD4 count of 150 cells/MUL or less, who have not received any tuberculosis
      treatment in the last three months, or ART in the last six months, are eligible.
      In intervention clinics, the study algorithm is used to classify individuals as
      at high, medium or low probability of tuberculosis. Those classified as high
      probability start tuberculosis treatment immediately, followed by ART after two
      weeks. Medium-probability patients follow the South African guidelines for test
      negative tuberculosis and are reviewed within a week, to be re-categorised as low
      or high probability. Low-probability patients start ART as soon as possible. The
      primary outcome is all-cause mortality at six months. Secondary outcomes include
      severe morbidity, time to ART start and cost-effectiveness. DISCUSSION: This
      trial will test whether a primary care-friendly management algorithm will enable
      nurses to identify HIV-positive patients at the highest risk of tuberculosis, to
      facilitate prompt treatment and reduce early mortality. There remains an urgent
      need for better diagnostic tests for tuberculosis, especially for people with
      advanced HIV disease, which may render empirical treatment unnecessary. TRIAL
      REGISTRATION: This trial was registered with Current Controlled Trials
      (identifier: ISRCTN35344604 ) on 12 September 2012.

PMID- 25872502
TI  - A pilot feasibility, safety and biological efficacy multicentre trial of
      therapeutic hypercapnia after cardiac arrest: study protocol for a randomized
      controlled trial.
AB  - BACKGROUND: Cardiac arrest causes ischaemic brain injury. Arterial carbon dioxide
      tension (PaCO2) is a major determinant of cerebral blood flow. Thus, mild
      hypercapnia in the 24 h following cardiac arrest may increase cerebral blood flow
      and attenuate such injury. We describe the Carbon Control and Cardiac Arrest
      (CCC) trial. METHODS/DESIGN: The CCC trial is a pilot multicentre feasibility,
      safety and biological efficacy randomized controlled trial recruiting adult
      cardiac arrest patients admitted to the intensive care unit after return of
      spontaneous circulation. At admission, using concealed allocation, participants
      are randomized to 24 h of either normocapnia (PaCO2 35 to 45 mmHg) or mild
      hypercapnia (PaCO2 50 to 55 mmHg). Key feasibility outcomes are recruitment rate
      and protocol compliance rate. The primary biological efficacy and biological
      safety measures are the between-groups difference in serum neuron-specific
      enolase and S100b protein levels at 24 h, 48 h and 72 h. Secondary outcome
      measure include adverse events, in-hospital mortality, and neurological
      assessment at 6 months. DISCUSSION: The trial commenced in December 2012 and,
      when completed, will provide clinical evidence as to whether targeting mild
      hypercapnia for 24 h following intensive care unit admission for cardiac arrest
      patients is feasible and safe and whether it results in decreased concentrations
      of neurological injury biomarkers compared with normocapnia. Trial results will
      also be used to determine whether a phase IIb study powered for survival at 90
      days is feasible and justified. TRIAL REGISTRATION: Australian New Zealand
      Clinical Trials Registry ACTRN12612000690853 .

PMID- 25872503
TI  - SMS-based smoking cessation intervention among university students: study
      protocol for a randomised controlled trial (NEXit trial).
AB  - BACKGROUND: Most smoking efforts targeting young people have so far been focused
      on prevention of initiation, whereas smoking cessation interventions have largely
      been targeted towards adult populations. Thus, there is limited evidence for
      effective smoking cessation interventions in young people, even though many young
      people want to quit smoking. Mobile communication technology has the potential to
      reach large numbers of young people and recent text-based smoking cessation
      interventions using phones have shown promising results. METHODS/DESIGN: The
      study aims to evaluate a newly developed text-based smoking cessation
      intervention for students in colleges and universities in Sweden. The design is a
      randomised controlled trial (RCT) with a delayed/waiting list intervention
      control condition. The trial will be performed simultaneously in all colleges and
      universities served by 25 student health care centres in Sweden. Outcomes will be
      evaluated after 4 months, with 2 cessation primary outcomes and 4 secondary
      outcomes. After outcome evaluation the control group will be given access to the
      intervention. DISCUSSION: The study will examine the effectiveness of a stand
      alone SMS text-based intervention. The intervention starts with a motivational
      phase in which the participants are given an opportunity to set a quit date
      within 4 weeks of randomisation. This first phase and the subsequent core
      intervention phase of 12 weeks are totally automated in order to easily integrate
      the intervention into the daily routines of student and other health care
      settings. As well as providing data for the effectiveness of the intervention,
      the study will also provide data for methodological analyses addressing a number
      issues commonly challenging in Internet-based RCTs. For example, an extensive
      follow-up strategy will be used in order to evaluate the use of repeated attempts
      in the analysis, and in particular to explore the validity of a possible missing
      not at random assumption that the odds ratio between the primary outcome and
      response is the same at every attempt. TRIAL REGISTRATION:  ISRCTN:
      ISRCTN75766527, dated assigned 4 November 2014. Protocol version: Version 1, and
      date 7 November 2014.

PMID- 25872504
TI  - WARRIOR-trial - is routine radiography following the 2-week initial follow-up in
      trauma patients with wrist and ankle fractures necessary: study protocol for a
      randomized controlled trial.
AB  - BACKGROUND: Extremity fractures such as wrist and ankle fractures are a common
      and costly healthcare problem. The management of these fractures depends on
      fracture type and loss of congruity of the joint, resulting in cast
      immobilization or operative treatment. Loss of congruity or displacement leading
      to uneven joint loading, osteoarthritis and an increased probability of a poor
      functional outcome should be identified within the first 2 weeks post-trauma,
      based upon radiographs to determine optimal treatment. After this period, routine
      radiographs are scheduled for monitoring the bone-healing process. Current
      protocols describe imaging at 1, 2, 6 and 12 weeks post-trauma. However, it is
      questionable whether routine radiography following the initial follow-up ( 2
      weeks post-trauma) is cost effective. The aim of this study is to determine
      whether a modification of the radiographic follow-up protocol can be conducted
      with no worse outcome and less cost than the current standard of care for
      patients with a wrist or ankle fracture. METHODS/DESIGN: In a multicenter
      randomized controlled trial, 697 patients aged 18 years or older will be
      included: 385 wrist fracture- and 312 ankle fracture patients. Patients will be
      randomized into two groups: Group 1 receives usual care, consisting of
      radiographs 1, 2, 6 and 12 weeks post-trauma; Group 2 receives radiographs beyond
      the initial follow-up only when clinically indicated. The primary outcome is the
      overall extremity-specific function. For wrist fractures, this includes the
      Disabilities of the Arm, Shoulder and Hand Score; for the ankle fractures, this
      includes the Olerud and Molander ankle score. Secondary outcomes include:
      healthcare cost, the specific function measured with the Patient Rated Wrist and
      Hand Evaluation for wrist fractures and American Academy of Orthopaedic Surgeons
      foot and ankle questionnaire for ankle fractures, pain-intensity, health-related
      quality of life, self-perceived recovery, and complications. Both groups will be
      monitored at 1, 2, and 6 weeks and 3, 6, and 12 months. DISCUSSION: This study
      will provide data on (cost) effectiveness of routine radiography in the follow-up
      of wrist and ankle fractures, and could pave the way for a change in
      (inter)national protocols. TRIAL REGISTRATION: Netherlands Trial Register NTR4610
      , registration date 22 June 2014.

PMID- 25872505
TI  - Enhancing inpatient psychotherapeutic treatment with online self-help: study
      protocol for a randomized controlled trial.
AB  - BACKGROUND: Depression is one of the most debilitating and costly mental
      disorders. There is increasing evidence for the efficacy of online self-help in
      alleviating depression. Knowledge regarding the options of combining online self
      help with inpatient psychotherapy is still limited. Therefore, we plan to
      evaluate an evidence-based self-help program (deprexis(r); Gaia AG, Hamburg,
      Germany) to improve the efficacy of inpatient psychotherapy and to maintain
      treatment effects in the aftercare period. METHODS/DESIGN: Depressed patients (n
      = 240) with private internet access aged between 18 and 65 are recruited during
      psychosomatic inpatient treatment. Participants are randomized to an intervention
      or control group at the beginning of inpatient treatment. The intervention group
      (n = 120) is offered an online self-help program with 12 weekly tasks, beginning
      during the inpatient treatment. The control group (n = 120) obtains access to an
      online platform with weekly updated information on depression for the same
      duration. Assessments are conducted at the beginning (T0) and the end of
      inpatient treatment (T1), at the end of intervention (T2) and 6 months after
      randomization (T3). The primary outcome is the depression score measured by the
      Beck Depression Inventory-II at T2. Secondary outcome measures include anxiety,
      self-esteem, quality of life, dysfunctional cognitions and work ability.
      DISCUSSION: We expect the intervention group to benefit from additional online
      self-help during inpatient psychotherapy and to maintain the benefits during
      follow-up. This could be an important approach to develop future concepts of
      inpatient psychotherapy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier:
      NCT02196896 (registered on 16 July 2014).

PMID- 25872506
TI  - Transcutaneous electrical stimulation at auricular acupoints innervated by
      auricular branch of vagus nerve pairing tone for tinnitus: study protocol for a
      randomized controlled clinical trial.
AB  - BACKGROUND: Subjective tinnitus is a phantom sensation experienced in the absence
      of any source of sound. Its mechanism remains unclear, and no approved drugs are
      available. Vagus nerve stimulation (VNS) is an exciting new method to treat
      tinnitus, but direct electrical stimulation of the cervical vagus has
      disadvantages. This randomized controlled clinical trial aims to overcome these
      limitations by stimulating the auricular branch of vagus nerve (ABVN) on the
      outer ear. Since the ABVN is the only peripheral branch of the vagus nerve
      distributed on the ear's surface, it should be possible to achieve analogous
      efficacy to VNS by activating the central vagal pathways. However, researches
      have indicated that the curative effect lies in a combination of auditory and
      vagal nerve stimulation. Moreover, from traditional Chinese theory, auricular
      acupoints used to treat tinnitus are mainly in the regions supplied by the ABVN.
      Whether stimulation at the auricular acupoints is due to unintentional
      stimulation of vagal afferent fibers also needs evidence. METHODS/DESIGN: A total
      of 120 subjects with subjective tinnitus are randomized equally into four groups:
      (1) electrical stimulation at auricular acupoints (CO10, CO11, CO12, and TF4)
      innervated by the ABVN; (2) electrical stimulation at auricular acupoints (CO10,
      CO11, CO12, and TF4) innervated by ABVN pairing tones; (3) electrical stimulation
      at auricular acupoints innervated by non-ABVN pairing tones; (4) electrical
      acupuncture. Patients will be treated for 30 minutes every other day for 8 weeks.
      The primary outcome measure is the Tinnitus Handicap Inventory. The secondary
      outcome measure combines a visual analogue scale to measure tinnitus disturbance
      and loudness with the Hospital Anxiety and Depression Scale. Assessment is
      planned at baseline (before treatment) and in the 4th and 8th week, with further
      follow-up visits after termination of the treatment at the 12th week. Any adverse
      events will be promptly documented. DISCUSSION: Completion of this trial will
      help to confirm whether ABVN or the combination of ABVN and sound stimulus plays
      a more important role in treating tinnitus. Moreover, the result of this clinical
      trial will enhance our understanding of specific auricular acupoints. TRIAL
      REGISTRATION: Chinese Clinical Trials Register ChiCTR-TRC-14004940.

PMID- 25872507
TI  - The quantity-effect relationship and physiological mechanisms of different
      acupuncture manipulations on posterior circulation ischemia with vertigo: study
      protocol for a randomized controlled trial.
AB  - BACKGROUND: Recent experiments have demonstrated that different needling
      manipulations may induce variable effects via diverse physiological mechanisms. A
      previous study indicated that needling at Fengchi (GB 20) improved cerebral blood
      flow in patients with vertigo induced by posterior circulation ischemia (PCI). In
      this study, we aim to explore the quantity-effect relationship and the
      physiological mechanisms underlying different acupuncture manipulations in PCI
      patients with vertigo. METHODS/DESIGN: We propose a pragmatic randomized and
      controlled trial. All participants, outcome assessors, and statisticians will be
      blinded. A total of 144 eligible participants will be randomized into one of four
      treatment groups receiving acupuncture at Fengchi (GB 20) with different one
      minute manipulation parameters. Group 1 will receive twirling at a frequency of
      60 times per minute toward the contralateral outer canthus at a depth of 0.5 to
      0.8 cun. Group 2 will receive twirling at a frequency of 60 times per minute
      toward the Adam's apple at a depth of 0.5 to 0.8 cun. Group 3 will receive
      twirling at a frequency of 120 times per minute toward the contralateral outer
      canthus at a depth of 0.5 to 0.8 cun. Group 4 will receive twirling at a
      frequency of120 times per minute toward the Adam's apple at a depth of 0.5 to 0.8
      cun. Additional points will be added based on individualized pattern diagnoses.
      The participants will receive 14 acupuncture sessions over 3 to 4 weeks. The
      subjects will be assessed at two time points: baseline and post-treatment. The
      primary outcome measurements will include subjective measurements
      (Vertebrobasilar System Ischemic Neurological Impairment Scale, UCLA Dizziness
      Questionnaire, Activities of Daily Living Scale, and Psychological and Social
      Adaptation Scale) and objective measurements (Transcranial Doppler, carotid
      ultrasonography and changes in cerebral oxygenation) to reduce bias arising from
      the placebo effect. We will use metabolomics to investigate the mechanisms
      underlying the different manipulation parameters. DISCUSSION: This trial aims to
      explore the quantity-effect relationship between different acupuncture
      manipulations and their clinical effects. The results from this study may help
      explain the contradictory results found in acupuncture studies that practice
      different manipulations. TRIAL REGISTRATION: Chinese Clinical Trial Registry:
      ChiCTR-RTRCC-12002675 (registered on 14 November 2012).

PMID- 25872508
TI  - Association between divorce and risks for acute myocardial infarction.
AB  - BACKGROUND: Divorce is a major life stressor that can have economic, emotional,
      and physical health consequences. However, the cumulative association between
      divorce and risks for acute myocardial infarction (AMI) is unknown. This study
      investigated the association between lifetime exposure to divorce and the
      incidence of AMI in US adults. METHODS AND RESULTS: We used nationally
      representative data from a prospective cohort of ever-married adults aged 45 to
      80 years (n=15,827) who were followed biennially from 1992 to 2010. Approximately
      14% of men and 19% of women were divorced at baseline and more than one third of
      the cohort had >=1 divorce in their lifetime. In 200,524 person-years of follow
      up, 8% (n=1211) of the cohort had an AMI and age-specific rates of AMI were
      consistently higher in those who were divorced compared with those who were
      continuously married (P<0.05). Results from competing-risk hazard models showed
      that AMI risks were significantly higher in women who had 1 divorce (hazard
      ratio, 1.24; 95% confidence interval, 1.01-1.55), >=2 divorces (hazard ratio,
      1.77; 95% confidence interval, 1.30-2.41), and among the remarried (hazard ratio,
      1.35; 95% confidence interval, 1.07-1.70) compared with continuously married
      women after adjusting for multiple risk factors. Multivariable-adjusted risks
      were elevated only in men with a history of >=2 divorces (hazard ratio, 1.30; 95%
      confidence interval, 1.02-1.66) compared with continuously married men. Men who
      remarried had no significant risk for AMI. Interaction terms for sex were not
      statistically significant. CONCLUSIONS: Divorce is a significant risk factor for
      AMI. The risks associated with multiple divorces are especially high in women and
      are not reduced with remarriage.

PMID- 25872509
TI  - The relationship between emotional recognition ability and challenging behaviour
      in adults with an intellectual disability: a systematic review.
AB  - This review questions whether a relationship exists between emotional recognition
      ability and challenging behaviour in people with an intellectual disability. A
      search was completed of a number of databases to identify relevant articles, and
      these were then evaluated against defined criteria. Eight articles were reviewed
      and their aims, study methodology, samples, measurement tools and findings are
      discussed and evaluated. Overall, studies found no significant deficit in the
      emotional recognition abilities of those with challenging behaviour when they
      were asked to identify the emotions of others. Two areas for further
      investigation were identified. Firstly, to ascertain whether a bias for
      identifying anger or sadness is found in those with challenging behaviour, and
      secondly, to understand the role of context in recognition of emotions and the
      degree to which this is different in those who present with challenging
      behaviour. A critique relating to the research is provided and suggested clinical
      and research implications are put forward. 

PMID- 25872510
TI  - Sperm bank failed to reveal donor's criminal record and schizophrenia, couple
      alleges.

PMID- 25872511
TI  - Relapse in multiple sclerosis.

PMID- 25872512
TI  - Seroprevalence of hepatitis C and correlates of seropositivity among men who have
      sex with men in Vancouver, Canada: a cross-sectional survey.
AB  - OBJECTIVES: We sought to determine the prevalence of hepatitis C virus (HCV)
      infection among men who have sex with men (MSM) in Vancouver, Canada, and
      associations of risk behaviours with HCV serostatus. METHODS: We used data from
      the ManCount Study, a cross-sectional survey of MSM selected through a venue
      based, time-location sampling method. Bivariate analyses and multivariate
      logistic regression modelling were used to determine correlates of HCV
      seropositivity. Bivariate analyses of participants who reported no history of
      injection drug use (IDU) were used to explore sexual behaviours associated with
      HCV seropositivity. RESULTS: HCV seroprevalence was 4.9% (56/1132). Among HCV
      seropositive participants who responded to the question, 22.4% (11/49) were
      unaware of their HCV-seropositive status, 84.9% (45/53) reported a history of IDU
      and 60.7% (34/56) were HIV positive by dried blood spot. Multivariate modelling
      found previous IDU (adjusted OR (AOR): 26.30, 95% CI 11.15 to 62.03), receiving
      goods, drugs or money for sex (AOR 4.98, 95% CI 2.43 to 10.20) and current
      smoking (AOR 3.46, 95% CI 1.47 to 8.16) were associated with HCV seropositivity.
      Among MSM who reported no history of IDU, HCV seropositivity was associated with
      bleeding after receptive anal sex (p=0.001) and a previous diagnosis of
      gonorrhoea (p=0.007). CONCLUSIONS: HCV seroprevalence among a sample of MSM is
      higher than the general population and associated with a history of IDU. Among
      those who did not report IDU, we found evidence that suggests sexual exposure
      could be the route of transmission.

PMID- 25872514
TI  - Total score or subscales in scoring the acromegaly quality of life questionnaire:
      using novel confirmatory methods to compare scoring options.
AB  - CONTEXT: Impaired quality of life (QoL) is common in patients after long-term
      remission of acromegaly. The acromegaly QoL (AcroQoL) is a disease-specific QoL
      questionnaire for patients diagnosed with acromegaly. The summed total score is
      the most frequently used scoring method of the AcroQoL. However, the total score
      does not capture all of the aspects of QoL that are outlined by the World Health
      Organization (WHO). OBJECTIVE: The aim of the present study was to use novel and
      sophisticated confirmatory methods to identify the optimal number of subscales
      for the AcroQoL. DESIGN AND PATIENTS: Patients in remission from acromegaly were
      recruited from the Leiden University Medical Center and were asked to complete
      the AcroQoL (Dutch version) questionnaire (n=72). RESULTS: The three-subscale
      version of the AcroQoL consisted of subscales reflecting Physical Complaints,
      Appearance Issues, and Personal Relations Issues related to QoL. Model fit
      indices (i.e., comparative fit index and root mean square error of approximation)
      indicated that the three-subscale version represented the data better than the
      total score and two-subscale models did. A chi(2) difference test indicated that
      the three-subscale model was a significantly better fit than the total score and
      two-subscale models were (P<0.05). CONCLUSION: Model fit and comparison
      statistics indicate that the three-subscale model is a better scoring method than
      the total score and two-subscale versions of the AcroQoL are. The three-subscale
      version also better reflected the WHO's recommendation of using a
      multidimensional measure of QoL than the total score and two-subscale methods
      did. Therefore, it is recommended that values from the three-subscales of the
      AcroQoL be reported in future research.

PMID- 25872513
TI  - Using visual rating to diagnose dementia: a critical evaluation of MRI atrophy
      scales.
AB  - Visual rating scales, developed to assess atrophy in patients with cognitive
      impairment, offer a cost-effective diagnostic tool that is ideally suited for
      implementation in clinical practice. By focusing attention on brain regions
      susceptible to change in dementia and enforcing structured reporting of these
      findings, visual rating can improve the sensitivity, reliability and diagnostic
      value of radiological image interpretation. Brain imaging is recommended in all
      current diagnostic guidelines relating to dementia, and recent guidelines have
      also recommended the application of medial temporal lobe atrophy rating. Despite
      these recommendations, and the ease with which rating scales can be applied,
      there is still relatively low uptake in routine clinical assessments. Careful
      consideration of atrophy rating scales is needed to verify their diagnostic
      potential and encourage uptake among clinicians. Determining the added value of
      combining scores from visual rating in different brain regions may also increase
      the diagnostic value of these tools. 

PMID- 25872515
TI  - MANAGEMENT OF ENDOCRINE DISEASE: Management of pregnant patients with Cushing's
      syndrome.
AB  - Progress in the diagnosis and treatment of endocrine diseases has turned
      pregnancy into a possibility for women with such medical disorders, including
      Cushing's syndrome (CS). Nevertheless, despite its rarity, pregnancy in patients
      with CS can be troublesome because of the risk of maternal-fetal complications.
      Therefore, hypercortisolism, if present, should be surgically or medically
      controlled in most cases. Moreover, changes in the hypothalamic-pituitary-adrenal
      axis during normal pregnancy may mislead the diagnosis of CS during this period,
      because many laboratory assessments suggestive of CS may be present in normal
      pregnancy, with clinical features mimicking those seen in patients with CS. The
      aim of the present review is to update the diagnostic approach to this medical
      condition, mainly for pregnant women without previous diagnosis of CS, and to
      describe the therapeutic strategies for CS during pregnancy in order to minimize
      complications for both mother and fetus. 

PMID- 25872516
TI  - Nanobrick wall multilayer thin films grown faster and stronger using
      electrophoretic deposition.
AB  - In an effort to speed up the layer-by-layer (LbL) deposition technique,
      electrophoretic deposition (EPD) is employed with weak polyelectrolytes and clay
      nanoplatelets. The introduction of an electric field results in nearly an order
      of magnitude increase in thickness relative to conventional LbL deposition for a
      given number of deposited layers. A higher clay concentration also results with
      the EPD-LbL process, which produces higher modulus and strength with fewer
      deposited layers. A 20 quadlayer (QL) assembly of linear polyethyleneimine
      (LPEI)/poly(acrylic acid)/LPEI/clay has an elastic modulus of 45 GPa, tensile
      strength of 70 MPa, and thickness of 4.4 MUm. Traditional LbL requires 40 QL to
      achieve the same thickness, with lower modulus and strength. This study reveals
      how these films grow and maintain a highly ordered nanobrick wall structure that
      is commonly associated with LbL deposition. Fewer layers required to achieve
      improved properties will open up many new opportunities for this multifunctional
      thin film deposition technique. 

PMID- 25872517
TI  - Aneurysm coil embolization: cost per volumetric filling analysis and strategy for
      cost reduction.
AB  - BACKGROUND: One of the primary device expenditures associated with the
      endovascular treatment of aneurysms is that of detachable coils. Analyzing the
      cost efficiency of detachable coils is difficult, given the differences in
      design, implantable volume, and the presence of additives. However, applying a
      volume per cost metric may provide an index analogous to unit price found in
      grocery stores. METHODS: The price information for 509 different coils belonging
      to 31 different coil lines, available as of September 2013, was obtained through
      the inventory management system at the study site, and normalized to the price of
      the least expensive coil. Values were used to calculate the logarithmic ratio of
      volume over cost. RESULTS: Operator choice among coil sizes can vary the material
      costs by five-fold in a hypothetical aneurysm. CONCLUSIONS: The difference in
      coil costs as a function of cost per volume of coil can vary tremendously. Using
      the present pricing algorithms, using the longest available length at a
      particular helical dimension and system yields improved efficiency.

PMID- 25872518
TI  - Stent retrievers and acute stroke treatment: a rapid learning curve for
      experienced neurointerventional surgeons.

PMID- 25872519
TI  - Cognitive motor intervention for gait and balance in Parkinson's disease:
      systematic review and meta-analysis.
AB  - OBJECTIVE: We performed a systematic review and meta-analysis to assess the
      effect of cognitive motor intervention (CMI) on gait and balance in Parkinson's
      disease. DATA SOURCES: PubMed, Embase, Cochrane Library, CINAHL, Web of Science,
      PEDro, and China Biology Medicine disc. METHODS: We included randomized
      controlled trials (RCTs) and non RCTs. Two reviewers independently evaluated
      articles for eligibility and quality and serially abstracted data. A standardized
      mean difference +/- standard error and 95% confidence interval (CI) was
      calculated for each study using Hedge's g to quantify the treatment effect.
      RESULTS: Nine trials with 181 subjects, four randomized controlled trials, and
      five single group intervention studies were included. The pooling revealed that
      cognitive motor intervention can improve gait speed (Hedge's g = 0.643 +/- 0.191;
      95% CI: 0.269 to 1.017, P = 0.001), stride time (Hedge's g = -0.536 +/- 0.167;
      95% CI: -0.862 to -0.209, P = 0.001), Berg Balance Scale (Hedge's g = 0.783 +/-
      0.289; 95% CI: 0.218 to 1.349, P = 0.007), Unipedal Stance Test (Hedge's g =
      0.440 +/- 0.189; 95% CI: 0.07 to 0.81, P =0.02). CONCLUSIONS: The systematic
      review demonstrates that cognitive motor intervention is effective for gait and
      balance in Parkinson's disease. However, the paper is limited by the quality of
      the included trials.

PMID- 25872520
TI  - Parents' expressed emotion and mood, rather than their physical disability are
      associated with adolescent adjustment: a longitudinal study of families with a
      parent with multiple sclerosis.
AB  - OBJECTIVE: This study investigated the impact of the severity of parental
      multiple sclerosis, parents' expressed emotion and psychological well-being on
      offspring's psychological difficulties. DESIGN: A longitudinal study including
      baseline and 6-month follow-up data collected from parents and children.
      SUBJECTS: Adolescents (n=75), their parents with multiple sclerosis (n=56) and
      the partner without multiple sclerosis (n=40). MAIN MEASURES: Parents completed
      the Hospital Anxiety and Depression Scale and the Five Minutes Speech Sample, a
      standardised interview of expressed emotion towards their child. Parents with
      multiple sclerosis also completed the Expanded Disability Status Scale, a measure
      of illness severity. Adolescents completed the Strength and Difficulties
      Questionnaire, a self-report measure of psychological difficulties. RESULTS:
      Higher depression scores of the parents with multiple sclerosis at baseline
      correlated with increased adolescents' internalising symptoms at 6-month follow
      up (gammadep=0.31, P=.004). Higher expressed emotion scores of parents with
      multiple sclerosis at baseline were associated with increased adolescent
      externalising symptoms at 6-month follow-up (gammaEE=4.35, P=.052). There was no
      direct effect of severity, duration or type of multiple sclerosis on adolescents'
      adjustment at baseline or follow-up. CONCLUSIONS: Emotional distress and
      expressed emotion in parents with multiple sclerosis, rather than the severity
      and type of multiple sclerosis had an impact on adolescents' psychological
      difficulties.

PMID- 25872521
TI  - Prevalence, incidence and risk factors for overuse injuries of the wrist in young
      athletes: a systematic review.
AB  - BACKGROUND: Overuse wrist injuries can cause long-term symptoms in young athletes
      performing wrist-loading sports. Information on the prevalence, incidence and
      associated risk factors is required. PURPOSE: We aimed to review the prevalence
      and incidence of overuse wrist injuries in young athletes and to identify
      associated risk factors. We focused on popular wrist-loading youth sports
      gymnastics, tennis, field hockey, volleyball, judo and rowing. STUDY DESIGN:
      Systematic review. METHODS: We conducted a literature search on athletes aged <18
      years performing wrist-loading focus sports. Prevalence, incidence and/or risk
      factor ORs for overuse wrist injuries were extracted directly or calculated from
      reported data. RESULTS: The search identified six studies on prevalence, five on
      incidence, and one on risk factors. Prevalence rates were 32-73% for wrist pain
      and 10-28% for overuse wrist injury. Incidence rates were 7-9% for wrist pain and
      0.02-26% for overuse wrist injury. The three criteria associated with wrist pain
      were (with OR): age of 10-14 years (11.5), training intensity (1.2), and earlier
      onset of gymnastics training (1.97). CONCLUSIONS: Prevalence and incidence of
      overuse wrist injuries was high in multiple studies of gymnasts, and largely
      unknown in other wrist-loading focus sports. Three key risk factors for wrist
      pain in gymnasts were age between 10 and 14 years, earlier training commencement,
      and training intensity. Using 'wrist pain' in defining overuse, and further
      investigating risk factors can aid in identifying overuse wrist injuries in young
      athletes.

PMID- 25872522
TI  - Forming norms: informing diagnosis and management in sports medicine.

PMID- 25872523
TI  - Prevalence and antithrombotic management of atrial fibrillation in hospitalised
      patients.
AB  - OBJECTIVES: The objective of this study was to determine the prevalence of atrial
      fibrillation (AF) in a tertiary care centre, to describe the comorbidity profile
      of hospitalised patients with AF, and to evaluate the appropriateness of their
      maintenance antithrombotic management. METHODS: In a cross-sectional, descriptive
      study, all consenting hospitalised patients from 36 wards in a University
      hospital (excluding critical care units, psychiatric, maternity and paediatric
      wards) received an ECG on a single day. Also their charts were reviewed for key
      demographic and clinical data. For patients with AF, all factors and
      comorbidities comprising thromboembolic (CHA2DS2-VASc) and bleeding risk (HAS
      BLED) were listed. The appropriateness of long-term anticoagulant therapy was
      assessed according to the 2010 international guidelines (CHA2DS2-VASc score
      0=aspirin or no antithrombotic treatment; 1=aspirin or oral anticoagulant
      treatment (OAC); >=2=OAC). The response rate was 79.7%, that is, an ECG was
      performed in 636 of 812 eligible hospitalised patients. RESULTS: AF was present
      on ECG in 58 patients reflecting a 9.1% hospital point prevalence (95% CI 6.9% to
      11.3%). Of the remaining 587 participants, 49 had a history of AF. Hence, 107 AF
      cases were identified, yielding a total prevalence of 16.8% (95% CI 13.9% to
      19.7%). Patients with AF were detected in every hospital zone, with highest
      prevalence rates in zone 'thorax' (29.3% (95% CI 22.2% to 36.4%)) and 'internal
      medicine' (21.7% (95%CI 14.8% to 28.6%)). Patients with AF were older than
      patients without AF (78.7+/-10.3 years versus 62.7+/-15.9 years; p<0.001). The
      most common associated comorbidities were hypertension (63.6%) and valvular heart
      disease (58.9%). Most patients with AF were at high risk for stroke (CHA2DS2-VASc
      score >=2 in 92.5%). Overall, only 51.3% of all patients did receive appropriate
      anticoagulant long-term management, while 31% were undertreated and 17.7% were
      possibly overtreated. CONCLUSIONS: This hospital-based study revealed high AF
      prevalence rates (16.8%). Patients with AF were present in all hospital zones and
      almost all patients were at high risk for stroke. Anticoagulation management was
      likely inappropriate in 48.7%, indicating the need for better guideline
      implementation initiatives to guarantee hospital-wide optimised care for patients
      with AF.

PMID- 25872524
TI  - Clinical benefit from pharmacological elevation of high-density lipoprotein
      cholesterol: meta-regression analysis.
AB  - CONTEXT: Epidemiological evidence that the risk of coronary heart disease is
      inversely associated with the level of high-density lipoprotein cholesterol (HDL
      C) has motivated several phase III programmes with cholesteryl ester transfer
      protein (CETP) inhibitors. OBJECTIVES: To assess alternative methods to predict
      clinical response of CETP inhibitors. METHODS: Meta-regression analysis on
      raising HDL-C drugs (statins, fibrates, niacin) in randomised controlled trials.
      RESULTS: 51 trials in secondary prevention with a total of 167,311 patients for a
      follow-up >1 year where HDL-C was measured at baseline and during treatment. The
      meta-regression analysis showed no significant association between change in HDL
      C (treatment vs comparator) and log risk ratio (RR) of clinical endpoint (non
      fatal myocardial infarction or cardiac death). CETP inhibitors data are
      consistent with this finding (RR: 1.03; P5-P95: 0.99-1.21). A prespecified
      sensitivity analysis by drug class suggested that the strength of relationship
      might differ between pharmacological groups. A significant association for both
      statins (p<0.02, log RR=-0.169-0.0499*HDL-C change, R(2)=0.21) and niacin
      (p=0.02, log RR=1.07-0.185*HDL-C change, R(2)=0.61) but not fibrates (p=0.18, log
      RR=-0.367+0.077*HDL-C change, R(2)=0.40) was shown. However, the association was
      no longer detectable after adjustment for low-density lipoprotein cholesterol for
      statins or exclusion of open trials for niacin. CONCLUSIONS: Meta-regression
      suggested that CETP inhibitors might not influence coronary risk. The relation
      between change in HDL-C level and clinical endpoint may be drug dependent, which
      limits the use of HDL-C as a surrogate marker of coronary events. Other markers
      of HDL function may be more relevant.

PMID- 25872525
TI  - Correlation between age and MMSE in schizophrenia.
AB  - BACKGROUND: The Mini-Mental State Examination (MMSE) is widely used in
      schizophrenia, although normative data are lacking in this population. This
      review and meta-regression analysis studies the effect of aging on MMSE scores in
      schizophrenic patients. METHODS: We entered the search terms schizophrenia and
      MMSE in PubMed and PsychInfo. Bibliographies of pertinent articles were also
      examined. We included every study presenting the MMSE scores in schizophrenic
      patients along with a corresponding mean age. We conducted our analyses using
      simple linear regression weighted for the inverse of within-trial variance of the
      age variable, thus conferring more importance to studies with narrower age
      groups. RESULTS: We identified 56 articles (n = 5,588) published between 1990 and
      2012. The MMSE scores of schizophrenic patients decline by approximately 1 point
      for every four years (y = 34.939-0.247x, 95% Confidence Interval (CI) [-0.304, 
      0.189], R 2 = 0,545), which is five times the rate in the general population.
      Institutionalized patients account for a large proportion of this decline (y =
      37.603-0.308x, 95% CI [-0.349, -0.267], R 2 = 0.622) whereas community-dwelling
      patients are relatively stable throughout aging (y = 27.591-0.026x, 95% CI [
      0.074, 0.023], R 2 = 0.037). CONCLUSIONS: Subgroup analyses show different
      trajectories between institutionalized and outpatients with schizophrenia. The
      deterioration observed in institutionalized patients may have to do with greater
      illness severity, heavier medication load, vascular risk factors, and lack of
      stimulation in institutional settings. Studies documenting the role of these
      variables would be useful. Cognitive screening tools that assess executive
      functions would be interesting to study in schizophrenics, as they may reveal
      more subtle age-related cognitive changes not measured by the MMSE.

PMID- 25872526
TI  - Effect of zinc on high glucose-induced epithelial-to-mesenchymal transition in
      renal tubular epithelial cells.
AB  - Zinc (Zn) as an essential dietary element has been indicated in a number of
      protein functions in the prevention of numerous types of epithelial-to
      mesenchymal transition (EMT)-driven fibrosis in vivo. However, relatively little
      is known regarding its effect in the EMT of the renal tubular epithelial cells,
      which play an important role in renal tubulointerstitial fibrosis and is an
      important component of the renal injury that is associated with diabetic
      nephropathy. The present study investigated the effect of Zn on the high glucose
      (HG)-induced EMT in a normal rat kidney tubular epithelial cell line (NRK-52E
      cells) and the underlying molecular mechanisms by immunofluorescence staining and
      western blot analysis. The present study identified that 10 uM of Zn
      supplementation prevented EMT changes, such as the loss of E-cadherin and the
      increase in alpha-smooth muscle actin and vimentin expression. Conversely,
      depletion of Zn with N,N,N',N'-tetrakis (2-pyridylmethyl)ethylenediamine in these
      cells aggravated changes in HG-induced EMT markers. Additionally, 10 uM Zn
      supplementation inhibited HG-induced transforming growth factor-beta1
      overexpression and reactive oxygen species production. Of note, HG increased
      phosphatidylinositol 3-kinase/Akt (PI3K/Akt) and mitogen-activated protein kinase
      (MAPK) pathways activation and Zn reversed HG-induced expression of PI3K/Akt,
      extracellular-signal-regulated kinase (ERK) and p38 MAPK, as well as EMT
      proteins. Finally, inhibitors of PI3K/Akt, ERK and p38 MAPK, and Zn
      supplementation blocked the HG-induced EMT in NRK-52E cells. These results
      indicate that physiologically optimal levels of Zn can inhibit HG-induced EMT of
      the NRK-52E cells possibly through several mechanisms, including abrogation of HG
      induced oxidative stress, and PI3K/Akt, p38 MAPK and ERK activation in NRK-52E
      cells.

PMID- 25872527
TI  - Separating different contributions to the crystal-field parameters using Wannier
      functions.
AB  - We discuss the calculation of crystal-field splittings using Wannier functions
      and show how contributions to the crystal-field splitting that are due to
      hybridization with different ligand states can be separated from the bare Coulomb
      contribution by constructing sets of Wannier functions incorporating different
      levels of hybridization. We demonstrate this method using SrVO3 as a generic
      example of a transition metal oxide. We then calculate trends in the crystal
      field splitting for two series of hypothetical tetragonally distorted perovskite
      oxides and discuss the relation between the calculated 'electrostatic'
      contribution to the crystal field and the simple point charge model. Finally, we
      apply our method to the charge disproportionated 5d electron system CsAuCl3. The
      proposed procedure elucidates the way in which the negative charge transfer
      energy in this material leads to a reversal of the p-d ligand contribution to the
      crystal-field splitting such that the eg states of the nominally Au(3+) cation
      are energetically lower than the corresponding t2g states. 

PMID- 25872528
TI  - A novel compound against oncogenic Aurora kinase A overcomes imatinib resistance
      in chronic myeloid leukemia cells.
AB  - Drug resistance still represents a major obstacle to successful chronic myeloid
      leukemia (CML) treatment and novel compounds or strategies to override this
      challenging problem are urgently required. Here, we evaluated a novel compound
      AKI603 against oncogenic Aurora kinase A (Aur-A) in imatinib-resistant CML cells.
      We found that Aur-A was highly activated in imatinib-resistant KBM5-T315I cells.
      AKI603 significantly inhibited the phosphorylation of Aur-A kinase at Thr288,
      while had little inhibitory effect on BCR-ABL kinase in both KBM5 and KBM5-T315I
      cells. AKI603 inhibited cell viability, and induced cell cycle arrest with
      polyploidy accumulation in KBM5 and KBM5-T315I cells. Moreover, inhibition of Aur
      A kinase by AKI603 suppressed colony formation capacity without promoting obvious
      apoptosis. Importantly, AKI603 promoted cell differentiation in both CML cell
      types. Thus, our study suggested the potential clinical use of small molecule
      Aurora kinase inhibitor AKI603 to overcome imatinib resistance in CML treatment.

PMID- 25872529
TI  - Evaluator-blinded trial evaluating nurse-led immunotherapy DEcision Coaching In
      persons with relapsing-remitting Multiple Sclerosis (DECIMS) and accompanying
      process evaluation: study protocol for a cluster randomised controlled trial.
AB  - BACKGROUND: Multiple sclerosis is a chronic neurological condition usually
      starting in early adulthood and regularly leading to severe disability.
      Immunotherapy options are growing in number and complexity, while costs of
      treatments are high and adherence rates remain low. Therefore, treatment decision
      making has become more complex for patients. Structured decision coaching, based
      on the principles of evidence-based patient information and shared decision
      making, has the potential to facilitate participation of individuals in the
      decision-making process. This cluster randomised controlled trial follows the
      assumption that decision coaching by trained nurses, using evidence-based patient
      information and preference elicitation, will facilitate informed choices and
      induce higher decision quality, as well as better decisional adherence.
      METHODS/DESIGN: The decision coaching programme will be evaluated through an
      evaluator-blinded superiority cluster randomised controlled trial, including 300
      patients with suspected or definite relapsing-remitting multiple sclerosis,
      facing an immunotherapy decision. The clusters are 12 multiple sclerosis
      outpatient clinics in Germany. Further, the trial will be accompanied by a mixed
      methods process evaluation and a cost-effectiveness study. Nurses in the
      intervention group will be trained in shared decision-making, coaching, and
      evidence-based patient information principles. Patients who meet the inclusion
      criteria will receive decision coaching (intervention group) with up to three
      face-to-face coaching sessions with a trained nurse (decision coach) or
      counselling as usual (control group). Patients in both groups will be given
      access to an evidence-based online information tool. The primary outcome is
      'informed choice' after six months, assessed with the multi-dimensional measure
      of informed choice including the sub-dimensions risk knowledge (questionnaire),
      attitude concerning immunotherapy (questionnaire), and immunotherapy uptake
      (telephone survey). Secondary outcomes include decisional conflict, adherence to
      immunotherapy decisions, autonomy preference, planned behaviour, coping self
      efficacy, and perceived involvement in coaching and decisional encounters. Safety
      outcomes are comprised of anxiety and depression and disease-specific quality of
      life. DISCUSSION: This trial will assess the effectiveness of a new model of
      patient decision support concerning MS-immunotherapy options. The delegation of
      treatment information provision from physicians to trained nurses bears the
      potential to change current doctor-focused practice in Germany. TRIAL
      REGISTRATION: Current Controlled Trials (identifier: ISRCTN37929939 ), May 27,
      2014.

PMID- 25872530
TI  - Quality of randomized controlled trials reporting in the treatment of melasma
      conducted in China.
AB  - BACKGROUND: There is no existing report on the quality of randomized controlled
      trials (RCTs) of melasma treatment currently conducted in China. This study aims
      to assess the quality of RCT- reporting in the treatment of melasma conducted in
      China. METHODS: Several databases were searched from their inception through to
      August 2014. In order to rate the report quality, we scored 1 for the item if it
      was reported in CONSORT 2010 and 0 for the item if it was not definitely stated
      or was not clear. For overall quality score (OQS), 13 items were scored and
      calculated with a range of 0 to 13. Five items ('randomization', 'allocation
      concealment', 'blinding', 'baseline characteristics' and 'intention-to-treat
      (ITT) analysis') were scored and a key methodological index score (MIS) was
      calculated with a range of 0 to 5 for each trial. RESULTS: A total of 246
      relevant RCTs were included in the final analysis. The median OQS was 7, with a
      minimum of 4 and a maximum of 11. Some items' information was insufficient,
      especially in the categories of 'trial design', 'sample size', 'recruitment' and
      'ancillary analyses' with a positive rate of less than 20%. The median MIS was 1
      with a minimum of 0 and a maximum of 3. Some items' reporting was poor,
      especially in the categories of 'randomization', 'allocation concealment and
      implementation', 'blinding' and 'ITT analysis' with a positive rate of less than
      10%. The mean OQS increased by about 0.52 for manuscripts published in the period
      of 5-year increments (95% CI: 0.32 to 0.72; P < 0.001). With regard to the MIS,
      no variable was statistically significant in the ordinal regression model.
      CONCLUSION: The reporting quality of RCTs in the treatment of melasma conducted
      in China is not satisfactory especially in key methodological items. Reporting of
      RCTs in this field should meet and keep up with the standards of the CONSORT
      statement.

PMID- 25872531
TI  - The role of pre-existing cross-reactive antibodies in determining the efficacy of
      vaccination in humans: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Epidemic viral diseases have become more prevalent.. Among the
      various strategies to prevent such epidemics, vaccination is the most cost
      effective. However, populations that are immunized are typically already exposed
      to multiple previous vaccinations or natural infections. Studies from this and
      other laboratories have revealed that pre-existing dengue antibodies can either
      inhibit or enhance subsequent dengue infection depending on the pre-existing
      antibody levels. While cross-reactive antibody is potentially pathogenic in
      dengue, how it impacts immune response to vaccination is unclear. Aggregated at
      the site of vaccination and the respective draining lymph nodes are antigen
      presenting and immune regulatory cells that express Fc receptors and play pivotal
      roles in determining the magnitude and polarity of the immune response. Vaccine
      uptake by these antigen-presenting cells may thus be either inhibited or enhanced
      when vaccines are opsonized with cross-reactive antibodies. DESIGN: In view of
      the limited knowledge on how cross-reactive antibodies affect vaccination
      outcome, we propose a study that exploits the known cross reactivity between
      Japanese encephalitis (JE) virus antibody and yellow fever (YF) vaccine. We
      hypothesize that cross-reactive antibodies impact antibody response to YF at the
      point vaccination in a concentration-dependent manner by altering both vaccine
      uptake and the innate immune response by antigen presenting cells. We will
      structure an open-label clinical trial on sequential vaccination with JE and YF
      vaccines, with different time intervals between vaccinations. This would test
      immune response to YF vaccination in subjects with different titer of cross
      reactive JE vaccine-derived antibodies. The clinical materials obtained in the
      trial will drive basic laboratory investigations directed at elucidating how
      heterologous antibody affect vaccination at the molecular level. YF neutralizing
      antibody titer will be measured using plaque reduction neutralization test
      against the vaccine strain YF17D. Innate immune response will be characterized
      genetically using either microarray or digital PCR (or both). The innate immune
      response will also be characterized at the protein and metabolite level using
      Luminex bead technology and lipidomic/metabolomic approaches. DISCUSSION: This
      proposed study represents one of the first to examine the role of cross-reactive
      antibodies in modulating immune responses to vaccines, the findings of which may
      re-shape vaccination strategy. TRIAL REGISTRATION: Clinical Trials.gov
      registration number: NCT01943305 (3 September 2013).

PMID- 25872533
TI  - Unusual Case of Papillary Thyroid Carcinoma with Choroidal Metastasis.
AB  - BACKGROUND: The choroid is a rare site of thyroid cancer metastases, and has been
      described in patients with evidence of advanced breast, lung, and prostate
      carcinomas. To the authors' knowledge, only seven reported cases exist with
      choroidal metastasis secondary to papillary thyroid carcinoma (PTC). This study
      describes an additional patient with metastatic PTC with simultaneous appearance
      of choroidal mass and cutaneous deposits while on systemic therapy with a
      tyrosine kinase inhibitor (TKI). These infrequent sites of metastasis are
      typically associated with a dismal prognosis following the diagnoses. However,
      this patient has not shown evidence of choroid or cutaneous recurrence one year
      following local targeted and systemic therapy. PATIENT FINDINGS: The case is
      presented of a 70-year-old male with widely metastatic PTC to the lymph nodes,
      lung, and mediastinum who was found to have choroidal metastasis six years after
      his initial diagnosis. SUMMARY: The patient was asymptomatic and was found to
      have an incidental right choroidal mass on routine ophthalmology exam. Magnetic
      resonance imaging of the orbit revealed an isolated right choroid lesion
      suspicious for melanoma or metastasis. Concurrent to this discovery, he was noted
      to have progression of the lung and mediastinal disease along with new dermal
      lesions on the chest wall suspicious for dermal metastasis. Both the choroid and
      dermal metastases occurred while being on a TKI. Given his previous history of
      male breast carcinoma, a biopsy of the choroid was performed, which confirmed
      PTC. The patient developed endophthalmitis and subsequently underwent enucleation
      of the right eye. The choroid mass was completely excised, measured 3.5 mm*9.5 mm
      with negative margins, and histopathology was consistent with metastatic PTC.
      Pulmonary, mediastinal, and cutaneous lesions regressed after external beam
      radiation therapy, following which systemic therapy was changed to a different
      multikinase inhibitor. CONCLUSION: A rare and unique case is reported of
      choroidal metastasis from PTC that presented with concurrent new dermal
      metastasis in addition to lung and mediastinal lymph node progression.
      Furthermore, the patient developed choroid and dermal lesions while on a TKI and
      remained stable without recurrence in these regions after switching to an
      alternate multikinase inhibitor.

PMID- 25872532
TI  - Thyroxine in acute myocardial infarction (ThyrAMI) - levothyroxine in subclinical
      hypothyroidism post-acute myocardial infarction: study protocol for a randomised
      controlled trial.
AB  - BACKGROUND: Cardiac disease is the most common cause of morbidity and mortality
      in the United Kingdom. Even minor changes in thyroid hormone concentration may
      impact adversely on the cardiovascular system. Subclinical hypothyroidism (SCH)
      after admission for an acute cardiac problem has been associated with an increase
      in cardiac mortality and overall death. We have designed protocols for a
      prospective observational study to assess the association of thyroid function at
      the time of acute myocardial infarction (AMI) with cardiovascular outcomes, and a
      double-blinded randomised placebo-controlled trial of levothyroxine to evaluate
      its effect on LV function and vascular health. METHODS/DESIGN: ThyrAMI 1: This
      will be a prospective longitudinal observational study of patients with AMI that
      will be followed for 24 months to study the association between thyroid status at
      the time of AMI (within 24 hours of diagnosis) with vascular outcomes. ThyrAMI 2:
      This will be a prospective double-blinded randomised placebo-controlled trial of
      levothyroxine of 12 months duration in patients with AMI and SCH. SETTING:
      Patients will be recruited from five hospitals in the North East of England.
      PARTICIPANTS: One hundred patients with thyroid function tests within the
      subclinical hypothyroid range upon admission with an AMI and no previous history
      of thyroid disease. INTERVENTION: Levothyroxine will be administered at a
      starting dose of 25 mcg once daily, which will be increased at intervals if
      needed to maintain a TSH level between 0.4 to 2.5 mU/L, versus a placebo.
      RANDOMISATION: Participants will be randomized with a computerised randomisation
      algorithm, stratified by type of MI (NSTEMI versus STEMI), in a 1:1 ratio to
      levothyroxine therapy or placebo (as container or bottle numbers), starting
      within 21 (+/- 7) days of AMI. BLINDING: Assignment to either the LT4 or placebo
      arm will be double-blinded. OUTCOMES: The outcome will be the effect of
      levothyroxine on ventricular function, endothelial function and blood
      coagulability and rheology. DISCUSSION: There is evidence to suggest that
      treatment of SCH can improve cardiovascular parameters. Therefore, ThyrAMI 1 and
      ThyrAMI 2 will be the first trials investigating SCH in AMI to give a better
      insight into whether thyroid hormone levels are a key target for improving
      cardiovascular outcomes. TRIAL REGISTRATION: ISRCTN number: ISRCTN52505169 . Date
      of registration: 09/01/2015.

PMID- 25872535
TI  - Effects of bee venom against Propionibacterium acnes-induced inflammation in
      human keratinocytes and monocytes.
AB  - Propionibacterium acnes (P. acnes) cause inflammatory acne and play an important
      role in the pathogenesis of acne by inducing inflammatory mediators. P. acnes
      contributes to the inflammatory responses of acne by activating inflammatory
      cells, keratinocytes and sebocytes to secrete pro-inflammatory cytokines such as
      tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta and IL-8. Bee
      venom has traditionally been used in the treatment of certain immune-related
      diseases. However, there has not yet been a robust trial to prove the therapeutic
      effect of bee venom in skin inflammation. The aim of the present study was to
      investigate anti-inflammatory properties of bee venom in skin inflammation
      induced by P. acnes using keratinocytes (HaCaT) and monocytes (THP-1). P. acnes
      is known to stimulate the production of pro-inflammatory cytokines such as IL-1,
      IL-8, IL-12 and TNF-alpha. In the present study, the production of interferon
      gamma (IFN-gamma), IL-1beta, IL-8 and TNF-alpha was increased by P. acnes
      treatment in HaCaT and THP-1 cells. By contrast, bee venom effectively inhibited
      the secretion of IFN-gamma, IL-1beta, IL-8 and TNF-alpha. Furthermore, P. acnes
      treatment activated the expression of IL-8 and toll-like receptor 2 (TLR2) in
      HaCaT cells. However, bee venom inhibited the expression of IL-8 and TLR2 in heat
      killed P. acnes. Based on these results, it is concluded that bee venom has an
      effective anti-inflammatory activity against P. acnes in HaCaT and THP-1 cells.
      Therefore, we suggest that bee venom is an alternative treatment to antibiotic
      therapy of acne.

PMID- 25872536
TI  - Diagnosis and treatment of unexplained anemia with iron deficiency without overt
      bleeding.
AB  - A general overview is given of the causes of anemia with iron deficiency as well
      as the pathogenesis of anemia and the para-clinical diagnosis of anemia. Anemia
      with iron deficiency but without overt GI bleeding is associated with a risk of
      malignant disease of the gastrointestinal tract; upper gastrointestinal cancer is
      1/7 as common as colon cancer. Benign gastrointestinal causes of anemia are iron
      malabsorption (atrophic gastritis, celiac disease, chronic inflammation, and
      bariatric surgery) and chronic blood loss due to gastrointestinal ulcerations.
      The following diagnostic strategy is recommended for unexplained anemia with iron
      deficiency: conduct serological celiac disease screening with transglutaminase
      antibody (IgA type) and IgA testing and perform bidirectional endoscopy
      (gastroscopy and colonoscopy). Bidirectional endoscopy is not required in
      premenopausal women < 40 years of age. Small intestine investigation (capsule
      endoscopy, CT, or MRI enterography) is not recommended routinely after negative
      bidirectional endoscopy but should be conducted if there are red flags indicating
      malignant or inflammatory small bowel disease (e.g., involuntary weight loss,
      abdominal pain or increased CRP). Targeted treatment of any cause of anemia with
      iron deficiency found on diagnostic assessment should be initiated. In addition,
      iron supplementation should be administered, with the goal of normalizing
      hemoglobin levels and replenishing iron stores. Oral treatment with a 100-200 mg
      daily dose of elemental iron is recommended (lower dose if side effects), but 3-6
      months of oral iron therapy is often required to achieve therapeutic goals.
      Intravenous iron therapy is used if oral treatment lacks efficacy or causes side
      effects or in the presence of intestinal malabsorption or prolonged inflammation.
      Three algorithms are given for the following conditions: a) the paraclinical
      diagnosis of anemia with iron deficiency; b) the diagnostic work-up for
      unexplained anemia with iron deficiency without overt bleeding; and c) how to
      proceed after negative bidirectional endoscopy of the gastrointestinal tract.

PMID- 25872534
TI  - Orally active alphavbeta3 integrin inhibitor MK-0429 reduces melanoma metastasis.
AB  - Melanoma remains one of the most aggressive types of cancer with a historically
      low survival rate. The alphavbeta3 integrin is involved in the progression of
      malignant melanoma. In the present study, the efficacy of MK-0429, a selective
      inhibitor of the alphavbeta3 integrin, was evaluated for its potential in the
      prevention of melanoma metastasis. Female B6D2F1 mice injected via the tail vein
      with murine B16F10 melanoma developed lung metastases within ~10 days. In the
      first experiment, the prevention of lung metastasis was assessed in the model
      treated with either vehicle, MK-0429 at 100 and 300 mg/kg orally twice daily or
      cyclophosphamide at 300 mg/kg, i.p. once daily. Study endpoints included
      determination of the study time period to achieve metastasis in lungs in this
      model, evaluation of the health effects on the study animals, the total number of
      lung colonies identified and lung tumor area. Unlike cyclophosphamide, the MK
      0429 treatment did not lead to a significant weight reduction in mice. MK-0429 at
      100 and 300 mg/kg reduced the number of metastatic tumor colonies by 64 and 57%,
      respectively, and the high dose also reduced the tumor area by 60% as compared to
      the vehicle. The second experiment employed B16F10 luciferase-expressing cells to
      examine the de novo progression of melanoma metastasis over 15 days with
      bioluminescent imaging of mice treated with MK-0429 at 300 mg/kg as compared to
      the vehicle. Tumor burden progressively advanced in the lungs of the B16F10
      treated animals. However, MK-0429 reduced the progression of ventral and dorsal
      lung metastases by 22 and 38%, respectively, as compared to the vehicle, by study
      completion. Quantification of ex vivo tumor burden showed a 30-40% reduction in
      lung colonies by MK-0429. The two studies collectively demonstrated that MK-0429
      was safe and efficacious in significantly decreasing melanoma metastasis in the
      lungs. The results emphasized the potential of MK-0429 as a novel, therapeutic
      agent for the prevention of metastatic melanoma.

PMID- 25872537
TI  - Celiac disease: diagnosis and treatment.
AB  - This national clinical guideline approved by the Danish Society for
      Gastroenterology and Hepatology describes the diagnosis and treatment of celiac
      disease (CD) in adults. CD is a chronic immune-mediated enteropathy of the small
      intestine triggered by the ingestion of gluten-containing proteins, which are
      found in wheat, rye, and barley. The disease prevalence is 0.5-1.0%, but CD
      remains under-diagnosed. The diagnosis relies on the demonstration of lymphocyte
      infiltration, crypt hyperplasia, and villous atrophy in duodenal biopsies.
      Serology, malabsorption, biochemical markers, and identification of specific HLA
      haplotypes may contribute to CD diagnosis. Classical CD presents with diarrhoea
      and weight loss, but non-classical CD with vague or extraintestinal symptoms is
      common. The treatment for CD is a lifelong gluten-free diet (GFD), which, in the
      majority of patients, normalises the small intestinal mucosa and absorption.
      Adherence to a GFD usually requires dietary advice from a clinical dietician. The
      monitoring of antibody levels and malabsorption markers is crucial during follow
      up and allows for early treatment of disease complications. Important
      complications include osteoporosis, iron and vitamin deficiencies, and
      enteropathy-associated T-cell lymphoma.

PMID- 25872538
TI  - Danish national sedation strategy. Targeted therapy of discomfort associated with
      critical illness. Danish Society of Intensive Care Medicine (DSIT) and the Danish
      Society of Anesthesiology and Intensive Care Medicine (DASAIM).
AB  - Sedation of critically ill patients undergoing mechanical ventilation should be
      minimized or completely avoided. Only in selected situations is sedation
      indicated as first line therapy (increased intracranial pressure or therapeutic
      hypothermia). The critical care physicians primary objective should be to focus
      on the reversible causes of agitation, such as: pain, anxiety, delirium, dyspnea,
      withdrawal symptoms, sleep or gastrointestinal symptoms. If sedation is used a
      validated sedation scale is recommended. On a daily basis sedation should be
      interrupted and only restarted after a thorough search for reversible causes of
      discomfort and stress.

PMID- 25872539
TI  - Migration and health: exploring the role of migrant status through register-based
      studies.
AB  - This thesis aims to explore migrant status as a determinant in register-based
      studies on migrant health. It is based on eight studies that investigate the
      following three main issues: 1) What is the importance of migrant status for
      morbidity patterns among migrants compared with Native Danes? 2) Do migrant
      status and ethnicity affect clinical indicators of access among migrants compared
      with native Danes? 3) What is the importance of migrant status for mortality
      patterns among migrants compared with Native Danes? The thesis builds on a
      register-based historical prospective cohort design. Through Statistics Denmark,
      all refugees (n = 29,174) and family reunification immigrants (n = 33,287) who
      received residence permits in Denmark from 1 January 1993 to 31 December 1999
      were included and matched 4:1 on age and sex with Native Danes. Register linkage
      was obtained twice during follow-ups in 2004 and 2008 respectively. Personal
      identification numbers were cross-linked to the Danish Psychiatric Central
      Register, the National Patient Registry, the Registry of Coercive Measures in
      Psychiatric Treatment, the Register of Causes of Death, and the Danish Cancer
      Registry. Migrant status defined by legal grounds for obtaining a residence
      permit was dichotomised into refugees and family reunification immigrants and
      used as the determinant in most studies. Analyses involved both Poisson and Cox
      regression analysis. Most analyses were stratified by ethnicity and adjusted for
      age and sex. Some were also stratified for individual income. Three sub-themes
      were investigated: morbidity, clinical indicators of access, and mortality. The
      first sub-theme (Papers I-III) showed that refugees had a consistently higher
      morbidity from several mental health disorders in contrast to family
      reunification immigrants, whose morbidity from mental disorders was lower than or
      similar to native Danes. The cancer incidence study did not find an effect of
      migrant status but found, rather, that migrants from the Middle East and North
      Africa had a lower cancer risk and that Eastern European migrants had a similar
      cancer risk compared with native Danes. The second sub-theme (Papers IV-VI)
      focused on different proxy measures of clinical indicators of access. Use of
      coercion was generally higher among migrants - especially refugee men and
      immigrant women - compared with native Danes. For cancer stage at diagnosis,
      migrants in general showed an unfavourable tendency towards more non-local versus
      local stages and more unknown versus known stages. No consistent patterns were
      found according to migrant status.The third sub-theme on mortality (Papers VI
      VIII) found that refugees - especially family reunification immigrants - had
      lower all-cause mortality and lower mortality from cancer, cardiovascular
      disease, and injuries. In contrast, refugees in particular and migrants in
      general had a higher mortality from infectious disease. The thesis demonstrates
      the unique opportunities for performing register-based research in Denmark,
      particularly in relation to migrants. It also demonstrates the role of migrant
      status as a useful variable in migrant studies in addition to ethnicity. Across
      all three sub-themes, inequalities in morbidity patterns were sometimes in favour
      of migrants and sometimes in favour of native Danes. Finally, inequalities in
      health were more pronounced for the refugee group, which was consistently more at
      risk compared with native Danes or which apparently benefited less from the
      protective factors of being a migrant compared with family reunification
      immigrants.

PMID- 25872540
TI  - Oxidative and inflammatory biomarkers of ischemia and reperfusion injuries.
AB  - Ischemia-reperfusion injuries occur when the blood supply to an organ or tissue
      is temporarily cut-off and then restored. Even though the restoration of blood
      flow is absolutely essential in preventing tissue death, the reperfusion of
      oxygenated blood to the oxygen-deprived areas may in itself augment the tissue
      damage in excess of that produced by the ischemia alone. The process of ischemia
      reperfusion is multifactorial and there are several mechanisms involved in the
      pathogenesis. Ample evidence shows that the injury is in part caused by an
      excessive generation of reactive oxygen species or free radicals. The free
      radicals consequently initiate an inflammatory response, which in some cases may
      affect distant organs, thus causing remote organ injuries. Ischemia-reperfusion
      injuries are a common complication in many diseases (acute myocardial
      infarctions, stroke) or surgical settings (transplantations, tourniquet-related
      surgery) and they have potential detrimental and disabling consequences. The
      tolerance of ischemia-reperfusion has proven to be time-of-day-dependent and the
      size of myocardial infarctions has proven to be significantly higher when
      occurring in the dark-to-light period. This period is characterized by and
      coincides with a rapid decrease in the plasma levels of the hormone melatonin.
      Melatonin is the body's most potent antioxidant and is capable of both direct
      free radical scavenging and indirect optimization of other anti-oxidant enzymes.
      It also possesses anti-inflammatory properties and is known to inhibit the
      mitochondrial permeability transition pore during reperfusion. This inhibiting
      property has been shown to be of great importance in reducing ischemia
      reperfusion injuries. Furthermore, melatonin is a relatively non-toxic molecule,
      which has proven to be safe for use in clinical trials. Thus, there is compelling
      evidence of melatonin's effect in reducing ischemia-reperfusion injuries in many
      experimental studies, but the number of human clinical trials is very limited. In
      this PhD thesis we set out to explore the oxidative and inflammatory biochemical
      markers of ischemia and reperfusion injuries and the possible effect of melatonin
      on these markers. We have reviewed the literature on the tourniquet-related
      oxidative damage and found that ischemic preconditioning and the use of propofol
      could significantly reduce the release of such markers. However, the relevance of
      this reduction in terms of clinical outcomes is still to be investigated (paper
      1). We undertook the characterization of a human ischemia-reperfusion model
      without the influencing factors of surgery and anesthesia, and subsequently found
      ways to improve this model (paper 2). In order to apply an intracoronary
      melatonin administration, we investigated whether melatonin could be dissolved in
      non-ethanol based buffers and still activate the melatonin receptors (paper 3).
      We found this to be possible, and in a porcine closed-chest model of acute
      myocardial infarction (AMI) we randomized the pigs to intracoronary and systemic
      melatonin or placebo in order to test whether melatonin could attenuate the
      oxidative and inflammatory biomarkers following reperfusion (paper 4). The
      outcomes were not optimal for this model, and the effect of melatonin still
      remains to be explored in a large animal model. We are currently still awaiting
      the results of the IMPACT-trial - a randomized, placebo-controlled, clinical
      trial exploring the effect of intracoronary and systemic melatonin given to
      patients suffering from AMI and undergoing primary percutaneous coronary
      intervention (pPCI) (paper 5). Though pPCI is undisputedly life-saving, it holds
      a built-in consequence of aggravating the ischemic injury, paradoxically due to
      the reperfusion. The optimization of existing treatments and the exploring of new
      suitable interventions, such as melatonin, for minimizing the ischemia
      reperfusion injuries is therefore of great interest. 

PMID- 25872541
TI  - Mechanisms of improved glycaemic control after Roux-en-Y gastric bypass.
AB  - Roux-en-Y gastric bypass (RYGB) surgery induces weight loss of 20-30% that is
      maintained for 20 years. In patients with type 2 diabetes, the glucose-lowering
      effect of RYGB is superior to conventional antidiabetic therapy and often occurs
      within days after surgery. The aim of the thesis was to investigate the
      physiological mechanisms responsible for improved glycaemic control with special
      focus on the early postoperative period. We therefore investigated insulin
      sensitivity, insulin clearance and pancreatic islet-cell function in patients
      with type 2 diabetes and in glucose tolerant subjects prior to and at 1 week, 3
      months and 1 year after RYGB. Hepatic insulin sensitivity measured with a glucose
      tracer increased already 1 week after RYGB, whereas peripheral insulin
      sensitivity estimated with the hyperinsulinaemic euglycaemic clamp was unchanged.
      Concomitant increases in insulin clearance at 1 week further highlights the liver
      as an important organ responsible for the early effects on glucose metabolism
      after surgery since insulin predominantly is cleared by the liver. Rapid
      improvements in hepatic insulin sensitivity is a common observation after calorie
      restriction in obese patients and has been observed as early as after 48 hours in
      absence of major weight loss and changes in peripheral insulin sensitivity. Thus,
      calorie restriction is a likely explanation for our findings of early
      improvements in hepatic insulin sensitivity and insulin clearance after RYGB.
      Peripheral insulin sensitivity increased along with weight loss at 3 months and 1
      year after RYGB. Beta-cell function increased after RYGB in patients with type 2
      diabetes in response to oral glucose, whereas insulin secretion was unchanged in
      response to an intravenous (iv) glucose-glucagon test throughout the first year
      after surgery. In glucose tolerant subjects, the insulin response to iv glucose
      glucagon declined after RYGB likely as an adaptation to increased insulin
      sensitivity. The secretion of glucagon-like peptide 1 (GLP-1) increased
      substantially in both groups in response to oral glucose, whereas the secretion
      of glucose-dependent insulinotropic poly-peptide (GIP) was largely unchanged
      postoperatively. The insulinotropic effects of the incretin hormones were
      preserved after surgery during iv infusion in glucose tolerant subjects.
      Increased insulin secretion postoperatively was thus linked to the oral and not
      the iv route of administration highlighting the importance of the changed
      gastrointestinal anatomy and the exaggerated GLP-1 secretion and not supporting
      major changes in intrinsic beta-cell function after RYGB. Changes in alpha-cell
      function did not seem to contribute substantially to the improved glycaemic
      control after RYGB, as glucagon secretion increased paradoxically after oral
      glucose, and suppression of glucagon in response to iv infusions of glucose, GIP,
      GLP-1 and insulin was largely unchanged postoperatively. In conclusion, improved
      glycaemic control after Roux-en-Y gastric bypass can be explained by early
      enhancements of hepatic insulin sensitivity and later improvements in peripheral
      insulin sensitivity in combination with increased postprandial insulin secretion
      linked to exaggerated postprandial GLP-1 secretion. Surgical changes in gut
      anatomy are likely to explain the increased GLP-1 secretion and hence the
      increased postprandial insulin secretion, whereas calorie restriction and
      subsequent weight loss may be the major cause of improved insulin sensitivity.

PMID- 25872542
TI  - The role of fibrinogen and haemostatic assessment in postpartum haemorrhage:
      preparations for a randomised controlled trial.
AB  - Pregnancy is a state of hypercoagulobility that might be an evolutionary way of
      protecting parturients from exsanguination following child birth. Observational
      studies suggest an association between a low level of fibrinogen (coagulation
      factor I) at the start of postpartum haemorrhage (PPH) and subsequent severity of
      bleeding. Fibrinogen concentrate may be prescribed to correct acquired
      hypofibrinogenaemia, but evidence is lacking regarding the treatment efficacy.
      This thesis assesses the current evidence for the use of fibrinogen concentrate
      and haemostatic assessment in bleeding patients with special attention to the
      obstetrical population. It includes five papers: In Paper I the benefits or harms
      of fibrinogen concentrate in bleeding patients in general was evaluated using a
      systematic Cochrane review methodology with metaanalysis of all published
      randomized controlled trials (RCTs). Six trials with high risk of bias were
      included (248 patients). Fibrinogen appeared to reduce the need of allogenic
      transfusions by 53%. However, the included trials were conducted only in an
      elective surgical setting with a population of mainly cardiac surgical patients.
      Paper II was also a systematic review based on Cochrane methodology evaluating
      the use of viscoelastic haemostatic assays to guide haemostatic transfusion in
      bleeding patients. Nine RCTs (776 patients) with high risk of bias were included
      primarily in elective cardiac surgical patients and none were specific for the
      obstetric subpopulation. Viscoelastic haemostatic assay guided transfusion
      algorithm reduced blood loss and the proportion of patients exposed to fresh
      frozen plasma (FFP) or platelets. In both studies, we were unable to make firm
      conclusion on our primary outcome, "all cause mortality" due to lack of adequate
      data. Paper III was based on two national Danish registries evaluating the
      predictability of postpartum blood transfusion. Prediction was found difficult.
      However, retained placental parts seemed to be the strongest predictor. Since
      this diagnosis is made very late and often in association with the onset of
      bleeding, tools to perform an early diagnosis is highly warranted. Paper IV
      includes recommendations of the European Society of Anaesthesiology regarding the
      use of fibrinogen concentrate in PPH, and is based on very weak (GRADE 2)
      evidence and low confidence in estimates of effect (GRADE C). Paper V describes
      the protocol for a RCT of early fibrinogen supplementation in women with severe
      postpartum haemorrhage. Several practical, ethical and trial management
      challenges need to be addressed when conducting independent clinical research
      involving parturients with severe bleeding, placebo-controlled and blinded
      administration of a drug in a multicenter set-up with enrolments during the
      entire day and with many personnel involved. 

PMID- 25872543
TI  - Aspirin in coronary artery disease: an appraisal of functions and limitations.
AB  - Aspirin (acetylsalicylic acid) is an antiplatelet drug used to treat and prevent
      coronary artery disease. Aspirin is used more frequently than any other drug in
      the world, however it does not inhibit platelet function equally well in all
      patients. The risk of platelet-dependent cardiovascular events is increased in
      patients, in whom aspirin inhibits platelet function suboptimally. Platelet
      inhibition with aspirin can be evaluated by use of modern whole blood platelet
      function tests. The overall aim of this dissertation was to identify and describe
      functions and limitations of aspirin. We used whole blood platelet aggregometry
      (Multiplate(r) Analyzer and VerifyNow(r) Aspirin) as the primary measure of
      platelet function. To identify biological mechanisms explaining our findings we
      also measured a number of biological markers, including markers of cyclooxygenase
      1 activity, platelet activation, and platelet turnover. All participants (except
      healthy individuals in study 1) were treated with non-enteric coated aspirin 75
      mg once daily during study participation and received no other drugs affecting
      platelet function. We used serum TXB2 measurements to verify that all patients
      were adherent to aspirin. In study 1, we investigated the association between
      platelet aggregometry results and platelet count, red blood cell count, and white
      blood cell count. The study population consisted of 417 aspirin-treated patients
      with stable coronary artery disease and 21 drug-naive healthy individuals. We
      found consistent associations between aggregation and platelet count, red blood
      cell count, and white blood cell count. In particular, platelet count was an
      independent predictor of platelet aggregation, although generally associations
      were rather weak. In study 2, we focused on patients previously suffering
      definite stent thrombosis because these patients may be at a prothrombotic state.
      We compared levels of platelet aggregation and platelet turnover in 39 patients
      with previous definite stent thrombosis with levels in 78 patients with stable
      coronary artery disease. We found that patients with previous definite stent
      thrombosis displayed increased platelet aggregation and had a tendency towards
      increased platelet turnover. In study 3, we investigated if the antiplatelet
      effect of aspirin is sustained through the standard 24-hour dosing interval. We
      included 50 patients with previous definite stent thrombosis, 100 patients with
      stable coronary artery disease, and 50 healthy individuals. We found that
      platelet aggregation increased significantly through the 24-hour dosing interval,
      and so did cyclooxygenase-1 activity and platelet activation. The increase in
      platelet aggregation did not differ between groups, but patients with previous
      definite stent thrombosis had higher levels of platelet turnover indices and
      thrombopoietin. In study 4, we addressed an ongoing debate concerning potential
      interactions between antiplatelet drugs and proton pump inhibitors. In patients
      with coronary artery disease, we investigated if the antiplatelet effect of
      aspirin was reduced in 54 patients treated with aspirin and a proton pump
      inhibitor compared to 364 patients treated with aspirin only. We found increased
      levels of platelet aggregation and platelet activation in patients treated with
      aspirin and a proton pump inhibitor.

PMID- 25872544
TI  - A cohort study of Danish patients with interstitial lung diseases: burden,
      severity, treatment and survival.
AB  - Interstitial lung diseases (ILDs) form a heterogeneous group of rare diseases
      characterised by varying degrees of pulmonary inflammation and fibrosis. We
      hypothesised that IPF and unclassifiable ILD were common in a Danish ILD cohort
      and that prognostic factors based on disease characteristics and comorbidities
      could be identified The aims of the PhD study were to describe the demographics
      of ILD in Central Denmark, to characterise the distribution of ILD diagnoses, and
      to assess prognostic factors in IPF and unclassifiable ILD. The study is based on
      a cohort of 431 ILD patients referred to our department during a 6-year period.
      All ILD diagnoses were re-evaluated according to current diagnostic criteria.
      Patients were followed from the time of first visit on suspicion of an ILD to the
      last visit to the centre, death, transplantation, or discharge from follow-up.
      The incidence of ILD was 4.1 per 100,000 inhabitants, and the incidence of IPF
      was 1.3 per 100,000 inhabitants in Central Den-mark. The most frequently
      occurring ILDs were IPF (28%), unclassifiable ILDs (extensive fibrotic disease
      and other unclassifiable ILDs) (24%), connective tissue disease-related ILD
      (14%), hyper-sensitivity pneumonitis (7%) and NSIP (7%). Cardiovascular dis-ease
      was present in 21% of the patients. The presence of cardio-vascular disease at
      the time of IPF diagnosis did not lead to increased mortality, whereas
      cardiovascular disease diagnosed during the course of IPF was a statistically
      significant predictor of mortality. Our study also showed that diabetes and
      concomitant anticoagulant therapy were associated with worse outcome in IPF, and
      that a simple HRCT scoring system could be used in the prediction of outcome in
      fibrotic ILDs. The study of unclassifiable ILD revealed two disease categories:
      one group characterised by extensive fibrotic disease and one characterised by
      more inflammatory features. The latter group was characterised by younger age and
      significantly better prognosis. We evaluated the pragmatic disease classification
      based on the clinical disease pattern included in the 2013 revision of the
      guidelines of diagnosis and treatment of interstitial lung diseases. We found
      that it was able to separate patients with unclassifiable ILD into categories
      with highly significant differences in survival. We also evaluated the ILD-GAP
      model, which is based on gender, age and pulmonary function (physiology), and
      found that it was a valuable predictor of survival in unclassifiable ILD. In a
      multivariate model, the two prediction scores showed significant individual
      contribution to the prognostic assessment. The present study has provided the
      first estimate of ILD and IPF incidence in the Danish population and has shown
      that demographics and survival of IPF in this cohort were comparable to what has
      been reported in other studies. Comorbidities were common among patients with
      IPF, and the results of the study have led us to believe that careful diagnosis
      and treatment of comorbidities are important in order to optimise outcome in
      patients with IPF, although our findings need to be confirmed in larger studies.
      Unclassifiable ILD is frequent in daily clinical practice but has not been
      characterised in detail. Our study showed that it was possible to identify
      predictors of outcome and to validate the ILD-GAP model in this cohort. The study
      also showed that the Disease Behaviour Classification can be used in the
      management of patients with unclassifiable ILD.

PMID- 25872545
TI  - Municipality-based physical rehabilitation after acute hip fracture surgery in
      Denmark.
AB  - INTRODUCTION: Patients who are surgically treated for an acute hip fracture in
      Denmark commence early in-hospital physical rehabilitation (PR) with more than
      95% of patients referred to further PR following discharge. However, the
      specifics of the PR services after discharge are unknown. Thus, the aim of the
      present paper was to describe the specifics of PR provided to patients following
      discharge after hip fracture (HF) surgery in Denmark to evaluate the need for
      future interventions or guidelines. METHODS: This was a national, cross-sectional
      questionnaire survey including 56 randomly selected municipalities out of 98.
      Information was gathered on PR and categorised into outpatient PR (including one
      to-one and group), home-based PR, 24-hour in-patient PR units and nursing homes.
      RESULTS: Sixty PR centres (97%) within 51 municipalities (91%) participated. The
      PR was initiated within 1-2 weeks after the municipality had received a referral
      from the hospital in 97% of the participating centres. The duration of PR was 8
      12 weeks or 4-7 weeks in 85% of the centres, and most often comprised 1-2
      training sessions per week. In all, 72% out of 56 municipalities returned a
      specific PR programme of which only 14% provided specific information regarding
      the intensity and the progression of training. CONCLUSION: PR after hip fracture
      in Denmark is initiated shortly after referral, for a variable duration of time
      and with poorly described exercise intensity and progression. This calls for a
      national description and implementation of an optimised PR programme according to
      the best available evidence. FUNDING: The study was supported by grants from The
      IMK Foundation, The Research Foundation of the Capital Region, The Research
      Foundation of the Danish Physical Therapy Organization, The Research Foundation
      of Hvidovre Hospital and The UCSF Lundbeck Foundation. The funding agencies had
      no influence on the study design, methods, subjects, data collection, analyses or
      on the manuscript. TRIAL REGISTRATION: not relevant.

PMID- 25872546
TI  - Knowledge and opinions on oncoplastic surgery among breast and plastic surgeons.
AB  - INTRODUCTION: More than 4,000 Danish women are diagnosed with operable breast
      cancer annually, and 70% receive breast conserving surgery. Without the use of
      oncoplastic surgery (OPS), 20-30% will get an unsatisfactory cosmetic result. The
      aim of this study was to illustrate the level of implementation of OPS in
      Denmark. METHODS: An electronic questionnaire was sent to breast and plastic
      surgeons performing breast cancer treatment. The questionnaire included
      demographics, education, experience with operative procedures and opinions on
      OPS. RESULTS: The questionnaire was sent to 50 breast surgeons and 22 plastic
      surgeons; the response rate was 67%. All breast surgery units had an established
      cooperation with plastic surgeons. Most breast surgeons used unilateral
      displacement techniques; plastic surgeons also included breast reduction
      techniques and replacement with local flaps. Almost all symmetrisation procedures
      were performed by plastic surgeons. Breast surgeons had sought more specific
      education, both international observerships and specific courses. In both groups
      of surgeons, the majority expressed that both tumour removal and reconstruction
      should be performed by doctors of their own specialty. CONCLUSION: OPS has become
      integrated in all breast centres, but has not yet been fully implemented. For
      optimal results in all patients, this study underlines the importance of the
      inclusion of a dedicated plastic surgeon within the multidisciplinary team for
      optimal initial evaluation of all breast cancer patients. FUNDING: not relevant.
      TRIAL REGISTRATION: not relevant.

PMID- 25872547
TI  - Outbreak of Pseudomonas aeruginosa bacteraemia in a haematology department.
AB  - INTRODUCTION: Infection by Pseudomonas aeruginosa represents a major cause of
      morbidity and mortality among immunocompromised patients. In Denmark, an increase
      in P. aeruginosa isolates from blood cultures from a haematology department
      prompted a hygienic audit in 2007. METHODS: Blood cultures that tested positive
      for P. aeruginosa were collected from the laboratory information system (MADS,
      Skejby Hospital, Aarhus, Denmark). Environmental samples were obtained from
      shower heads in the department. The genotype was established by pulse field gel
      electrophoresis (PFGE). An audit was conducted during the outbreak and 12 months
      later. The audits were conducted by the method of direct observation. RESULTS:
      Several PFGE types were involved with no clear association to isolates from
      environmental samples. The audit revealed poor hygiene related to the handling of
      central venous catheters. After optimising catheter hygiene, the number of P.
      aeruginosa bacteraemia cases fell significantly. CONCLUSION: Since no clear
      association between patient and environmental genotype was established, it was
      suspected that central venous catheters were the main portal of entry. This was
      further supported by a simultaneous decline in bacteraemia cases with coagulase
      negative staphylococci. Though several hygienic precautions were taken, the
      increased focus on disinfection of hubs and injection ports was presumably the
      more important element. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.

PMID- 25872548
TI  - Incidence and survival from lung cancer in Greenland is comparable to survival in
      the Nordic countries.
AB  - INTRODUCTION: Oncological treatment of lung cancer has been available in
      Greenland since 2004. We evaluated patient characteristics and survival rates for
      the first six years of local lung cancer treatment. METHODS: From September 2004
      to August 2010, a total of 173 patients with lung cancer were referred to
      treatment at Queen Ingrid's Hospital. On 1 February 2014, treatment results,
      survival, and prognostic variables were analysed. RESULTS: The mean age at
      diagnosis was 63 years. Non-small cell lung cancer (NSCLC) was diagnosed in 145
      patients (84%); 56% had squamous cell carcinoma, 34% had adenocarcinoma, 2% had
      large cell carcinoma and 8% had NSCLC not otherwise specified (NOS). In all, 28
      (16%) had small cell lung cancer. A total of 142 patients (82%) received
      treatment; 20 underwent surgery (ten stage Ib, one stage IIa, five stage IIb,
      four stage IIIa); palliative chemotherapy was given to 122 of the 142 treated
      patients (86%). Of these, 36 patients (30%) received second-line chemotherapy.The
      median survival of patients undergoing primary lobectomy/pneumonectomy,
      palliative chemotherapy, and no treatment was 76.3 months, 11.8 months, and 2.0
      months, respectively (p < 0.0001). CONCLUSION: Evaluation of the first six years
      of lung cancer treatment in Greenland revealed a disease incidence and survival
      comparable to those found in the Nordic countries. To further decrease mortality
      from lung cancer, health-care resources should continue to be allocated to the
      prevention and treatment of lung cancer in Greenland. FUNDING: not relevant.
      TRIAL REGISTRATION: not relevant.

PMID- 25872549
TI  - Suspected side effects to the quadrivalent human papilloma vaccine.
AB  - INTRODUCTION: The quadrivalent vaccine that protects against human papilloma
      virus types 6, 11, 16 and 18 (Q-HPV vaccine, Gardasil) was included into the
      Danish childhood vaccination programme in 2009. During the past years, a
      collection of symptoms primarily consistent with sympathetic nervous system
      dysfunction have been described as suspected side effects to the Q-HPV vaccine.
      METHODS: We present a description of suspected side effects to the Q-HPV vaccine
      in 53 patients referred to our Syncope Unit for tilt table test and evaluation of
      autonomic nervous system function. RESULTS: All patients had symptoms consistent
      with pronounced autonomic dysfunction including different degrees of orthostatic
      intolerance, severe non-migraine-like headache, excessive fatigue, cognitive
      dysfunction, gastrointestinal discomfort and widespread pain of a neuropathic
      character. CONCLUSION: We found consistency in the reported symptoms as well as
      between our findings and those described by others. Our findings neither confirm
      nor dismiss a causal link to the Q-HPV vaccine, but they suggest that further
      research is urgently warranted to clarify the pathophysiology behind the symptoms
      experienced in these patients and to evaluate the possibility and the nature of
      any causal link and hopefully establish targeted treatment options. FUNDING: not
      relevant. TRIAL REGISTRATION: not relevant.

PMID- 25872550
TI  - Treatment of hypoglycaemic diabetics in a prehospital setting is safe.
AB  - INTRODUCTION: Patients with diabetes suffering from hypoglycaemia may be treated
      by a Mobile Emergency Care Unit (MECU) and are often released at the scene
      following treatment. Some of these patients experience secondary hypoglycaemia
      and require renewed treatment or admission to hospital. The present study was
      initiated in order to investigate the extent of secondary hypoglycaemia, to
      evaluate the appropriateness of the current treatment practice, and to provide
      practical suggestions for the hand-ing of prehospital hypoglycaemia. METHODS: All
      MECU runs are registered in a database by the attending physician who states the
      patients' identity, treatment, outcome and diagnosis. Over a period of four years
      (1 May 2006-30 April 2010), all missions related to hypo-glycaemia were reviewed.
      Each entry was cross-referenced with the patient's hospital files to detect any
      recurrent hypoglycaemic episodes within 24 hours from initial contact. RESULTS:
      The MECU treated 138 hypoglycaemic cases of whom 50% were released at home
      following treatment. Four of these patients experienced secondary hypoglycaemia.
      Two were treated by the MECU and two were admitted through the emergency
      department without contact to the MECU. CONCLUSION: The number of patients
      suffering from secondary hypoglycaemia following treatment by the MECU is
      acceptable and in line with numbers reported by similar organisations. FUNDING:
      not relevant. TRIAL REGISTRATION: not relevant.

PMID- 25872551
TI  - Need for strengthened focus on cancer rehabilitation in Danish municipalities.
AB  - INTRODUCTION: Danish municipalities have recently been given a mandate to
      organise cancer rehabilitation services. Knowledge is therefore needed about the
      services provided and their utilisation. The aim of this national Danish baseline
      survey was to explore the availability, utilisation, content and organisation of
      municipal cancer rehabilitation services. METHODS: Electronic questionnaires were
      sent to all 98 Danish municipalities in January 2013. The questionnaire consisted
      of closed-ended and open-ended questions. Descriptive statistics and contents
      analysis were used. RESULTS: A total of 91 municipalities responded (93% response
      rate). Of these, 75% reported that they provided cancer rehabilitation services.
      The number of patients enrolled was below the estimated proportion of patients
      needing rehabilitation services. Services consisted predominantly of physical
      training in groups, followed by "stop smoking" courses, dietary advice, physical
      training guidance, patient education and individual physical training. Inequality
      in referral by ethnicity, age and gender was reported. Challenges encountered
      included low patient numbers, inadequate collaboration within and across sectors
      and lack of evidence-based models for cancer rehabilitation. CONCLUSION: There is
      a need for increased capacity and improved alignment between patients'
      rehabilitation needs and the available services. FUNDING: This study was funded
      by grants from The Centre for Integrated Rehabilitation of Cancer Patients
      (CIRE), and received support from The Danish Cancer Society and The Novo Nordisk
      Foundation. TRIAL REGISTRATION: not relevant.

PMID- 25872552
TI  - Higher rate of compensation after surgical treatment versus conservative
      treatment for acute Achilles tendon rupture.
AB  - INTRODUCTION: Acute Achilles tendon rupture (ATR) can be treated either
      surgically or non-surgically. High-quality meta-analyses show a lower re-rupture
      rate, but a higher overall complication rate among surgically treated patients.
      No studies have evaluated the socio-economic impact of different complications.
      The aim of this study was to investigate: 1) the socio-economic impact of
      complications after ATR through the utilisation of the Danish Patient Insurance
      Association (DPIA) database, 2) correlations between treatment and complications.
      METHODS: A total of 324 patients with ATR reported in the period from 1992 to
      2010 in the DPIA database were identified and patient records were reviewed
      manually. RESULTS: The compensation awarded for the 18-year period totalled
      18,147,202 DKK with 41% of patient claims being recognised. Out of 180 surgically
      treated patients, 79 received a total compensation of 14,051,377 DKK, median
      47,637 (range: 5,000-3,577,043). Of 114 non-surgically treated patients, 40
      received 3,715,224 DKK in compensation, with a median amount of 35,788 DKK
      (range: 5,000-830,073). CONCLUSION: Compensation after surgical treatment was 3.8
      times higher than compensation after non-surgical treatment. It is noteworthy
      that 34.5% of patients had an overlooked diagnosis which underlines the
      importance of a correct primary diagnosis. FUNDING: not relevant. TRIAL
      REGISTRATION: not relevant.

PMID- 25872553
TI  - Methicillin-resistant Staphylococcus aureus transmission: unrecognised patient
      MRSA carriage.
AB  - INTRODUCTION: Even though methicillin-resistant Staphylococcus aureus (MRSA) is a
      common cause of nosocomial infections, it may often be difficult to evaluate the
      exact route of transmission. METHODS: In this study, we describe four cases of
      nosocomial transmission of MRSA in a hospital with a low MRSA incidence. RESULTS:
      In one case, a multi-traumatic patient arrived from a hospital in a foreign
      country and the primary surveillance swaps were negative for MRSA. The second
      case was a child with burn wounds who was referred from a Danish hospital. The
      third case was a multi-traumatic patient from Denmark. The fourth case was a new
      born child in the neonate unit. CONCLUSION: In none of the cases, the index
      patient was known to have MRSA on admission and no specific precautions were
      taken to prevent transmission. In all cases there was intensive contact between
      the patient and the staff which may increase the risk of contaminating hands,
      arms and the front of the uniform. Hand hygiene is therefore essential, but the
      use of protection gowns with long sleeves is also important in order to prevent
      transmission of MRSA. After culture of MRSA and implementation of specific
      precautions to prevent transmission of MRSA, no further transmissions were
      observed. FUNDING: not relevant. TRIAL REGISTRATION: The data in this study are
      included in the routine surveillance of MRSA at Rigshospitalet and do not form
      part of a trial.

PMID- 25872554
TI  - Moderate and deep nurse-administered propofol sedation is safe.
AB  - INTRODUCTION: Non-anaesthesiologist-administered propofol sedation (NAPS/NAAP) is
      increasingly used in many countries. Most regimens aim for light or moderate
      sedation. Little evidence on safety of deep NAPS sedation is available. The aim
      of this study was to explore the safety of intermittent deep sedation with NAPS
      in patients undergoing gastroenterologic endoscopic procedures. METHODS: This was
      a retrospective case-control study. All patients sedated with NAPS for
      colonoscopies, sigmoidoscopies and oesophagogastroduodenoscopies from May 2007
      through December 2012 were included. Cases were defined as patients developing an
      adverse event (oxygen saturation < 92%, a drop in mean arterial pressure of > 30%
      or a drop in systolic blood pressure of > 50 mmHg). The remaining patients served
      as controls. RESULTS: A total of 6,840 consecutive patients undergoing 7,364
      procedures were included. The mean propofol dose was 331.6 mg (standard deviation
      = 179.4 mg). The overall rate of hypoxia was 3.2%, and the rate of hypotension
      was 3.1%. Assisted ventilation was needed in 0.5%. Age (p < 0.001), American
      Society of Anesthesiologists (ASA) class 3 (p = 0.017) and total propofol dose (p
      = 0.001) were associated with a higher rate of adverse events. CONCLUSION: Safety
      during intermittent deep sedation with NAPS was good. Age, ASA class 3 and total
      propofol dose were correlated with a higher rate of adverse events. Patients aged
      60 years or more needed more handling during adverse events. FUNDING: Arvid
      Nilsson's Foundation provided funding for this study. The founders did not have
      any influence on the design or the presentation of the study. TRIAL REGISTRATION:
      not relevant.

PMID- 25872555
TI  - Elevated costs and high one-year mortality in patients with diabetic foot ulcers
      after surgery.
AB  - INTRODUCTION: In Denmark, approximately 300,000 patients have a diabetes mellitus
      diagnosis. Recently published guidelines emphasise that health-care professionals
      who are in direct contact with citizens should be aware of the importance of
      prevention and early detection of diabetic foot ulcers. The objective of this
      study was to evaluate the mortality, length of hospital stay and economic impact
      on health care in patients with acute diabetic foot ulcers who were hospitalised
      in the Department of Orthopaedic Surgery, Aalborg University Hospital, Denmark.
      METHODS: This was a prospective cohort study including all patients admitted with
      a diagnosis of acute foot ulcer to the Department of Orthopaedic Surgery,
      Aalborg, Denmark, from September 2011 to February 2012. RESULTS: A total of 48
      patients were referred for surgical treatment of a diabetic foot ulcer. The
      average age on admission was 64 years (35-87 years). The median length of
      hospital stay was 17 days (3-150 days), and 14 patients were readmitted within
      the first year. Within the first year of enrolment, 13 patients died,
      corresponding to a 36% mortality rate. Based on the Danish Diagnosis-Related
      Groups rates, the median cost associated with a case in the study population was
      133,867 DKK. CONCLUSION: Patients referred for surgical revision of diabetic foot
      ulcers are often severely ill, and the condition is associated with a high one
      year mortality rate. Furthermore, the cost of these cases is considerable.
      Preventive interventions, early diagnosis and treatment and multidisciplinary
      interventions - before and during hospitalisation - should be implemented.
      FUNDING: not relevant. TRIAL REGISTRATION: The Danish Data Protection Agency (J.
      No. 2008-58-0028) approved the study.

PMID- 25872556
TI  - Factors affecting post-operative sleep in patients undergoing colorectal surgery 
      a systematic review.
AB  - INTRODUCTION: Understanding factors affecting post-operative recovery is of great
      importance to efforts at reducing morbidity and mortality after general surgery.
      Post-operatively, most patients suffer from objectively and subjectively
      measurable reduced sleep quality. We aimed to review the available literature on
      post-operative sleep in patients undergoing colorectal surgery. METHODS: This
      systematic review was conducted according to the PRISMA guidelines, searching the
      electronic data-bases PubMed, Embase and the Cochrane Library. All articles were
      evaluated according to pre-defined inclusion criteria. RESULTS: Five studies were
      included in the review. Sleep quality was affected by type of surgery (open or
      laparoscopic), the administration/mode of application of analgesics (epidural
      analgesia or continuous wound infusion) and the level of pain. Patients who
      listened to new age music and a "relaxing text" had better quality of post
      operative sleep than controls. Overall, pain interfered with subjective, post
      operative sleep quality and adequate treatment of pain improved subjective sleep
      quality. CONCLUSION: Sleep quality is sensitive to various factors in the
      perioperative period, and impairment of sleep quality can be prevented by simple
      improvements in perioperative care.

PMID- 25872557
TI  - Influenza vaccination in pediatric age.
AB  - To increase the protective efficacy against influenza in pediatric populations,
      several attempts to modify the composition or the route of administration of an
      inactivated influenza vaccine have been made. Adjuvants have been added, vaccines
      with higher antigen content have been developed and intradermal administration of
      inactivated influenza vaccine with a variety of devices has been considered. Such
      attempts to develop universal influenza vaccines will continue to be made. For
      some time, the knowledge that the licensed influenza vaccines induce strain
      specific immunity and may have low efficacy in unexpected outbreaks of new
      epidemic strains has motivated the development of preparations with broader and
      longer-lasting protection. Ideally, children would be included early in the
      evaluation of the efficacy of new vaccines to avoid lengthy delays in making the
      protection available to this vulnerable population. Moreover, further studies to
      clarify definitively whether protection of infants <6 months of age can be
      obtained through vaccination of the pregnant woman have to be performed. 

PMID- 25872558
TI  - The surprising activities of APOBEC3B and 5-fluorouracil.
AB  - In this mini-special issue on cancer, we learn how DNA editing enzymes can
      accelerate the development of cancer and we discover some remarkable effects of
      the chemotherapeutic agent, 5-fluorouracil, on the immune system. We also discuss
      a study revealing the continuing problem of vitamin B deficiencies in children in
      developing countries, and we determine how to distinguish two near-identical
      forms of necrotizing fasciitis. 

PMID- 25872559
TI  - Introduction to miniseries on DNA and cancer.

PMID- 25872560
TI  - The Surgeon's View: Comparison of Two Digital Video Recording Systems in
      Veterinary Surgery.
AB  - Video recording and photography during surgical procedures are useful in
      veterinary medicine for several reasons, including legal, educational, and
      archival purposes. Many systems are available, such as hand cameras, light
      mounted cameras, and head cameras. We chose a reasonably priced head camera that
      is among the smallest video cameras available. To best describe its possible uses
      and advantages, we recorded video and images of eight different surgical cases
      and procedures, both in hospital and field settings. All procedures were recorded
      both with a head-mounted camera and a commercial hand-held photo camera. Then
      sixteen volunteers (eight senior clinicians and eight final-year students)
      completed an evaluation questionnaire. Both cameras produced high-quality
      photographs and videos, but observers rated the head camera significantly better
      regarding point of view and their understanding of the surgical operation. The
      head camera was considered significantly more useful in teaching surgical
      procedures. Interestingly, senior clinicians tended to assign generally lower
      scores compared to students. The head camera we tested is an effective, easy-to
      use tool for recording surgeries and various veterinary procedures in all
      situations, with no need for assistance from a dedicated operator. It can be a
      valuable aid for veterinarians working in all fields of the profession and a
      useful tool for veterinary surgical education. 

PMID- 25872561
TI  - Veterinary School Applicants: Financial Literacy and Behaviors.
AB  - Each year the Association of American Veterinary Medical Colleges (AAVMC)
      conducts a survey after the close of the Veterinary Medical College Application
      Service (VMCAS) application. The survey provides a glimpse into applicant
      behavior surrounding the veterinary school application process. Additional survey
      questions probe into applicant financial behaviors, use of financial products and
      services, and pet ownership. This article examines the 2013 survey data from
      applicants who successfully completed the application, with a focus on applicant
      financial literacy and behaviors. Data from the study revealed a disconnect
      between applicants' perception of their ability to deal with day-to-day finances
      and their actual financial behaviors, particularly for first-generation college
      student applicants and applicants who are racially/ethnically underrepresented in
      veterinary medicine (URVM). Many applicants were not able to accurately report
      the average veterinary school graduate's student debt level, which suggests the
      potential need for better education about the costs associated with attending
      veterinary school. 

PMID- 25872562
TI  - Structural parameters effect on the electrical and electroluminescence properties
      of silicon nanocrystals/SiO2 superlattices.
AB  - The effect of the oxide barrier thickness (tSiO2) reduction and the Si excess
      ([Si]exc) increase on the electrical and electroluminescence (EL) properties of
      Si-rich oxynitride (SRON)/SiO2 superlattices (SLs) is investigated. The active
      layers of the metal-oxide-semiconductor devices were fabricated by alternated
      deposition of SRON and SiO2 layers on top of a Si substrate. The precipitation of
      the Si excess and thus formation of Si nanocrystals (NCs) within the SRON layers
      was achieved after an annealing treatment at 1150  degrees C. A structural
      characterization revealed a high crystalline quality of the SLs for all devices,
      and the evaluated NC crystalline size is in agreement with a good deposition and
      annealing control. We found a dramatic conductivity enhancement when the Si
      content is increased or the SiO2 barrier thickness is decreased, due to a larger
      interaction of the carrier wavefunctions from adjacent layers. EL recombination
      dynamics were studied, revealing radiative recombination decay times of the order
      of tens of microseconds. Lower lifetimes were found at higher [Si]exc, attributed
      to exciton confinement delocalization, whereas intermediate barrier thicknesses
      present the slowest decay. The electrical-to-light conversion efficiency
      increases monotonously at thicker barriers and smaller Si contents. We ascribe
      these effects mainly to free carriers, which enhance carrier transport through
      the SLs while strongly quenching light emission. Finally, the combination of the
      different results led us to conclude that tSiO2 ~ 2 nm and [Si]exc from 12 to 15
      at% are the ideal structure parameters for a balanced electro-optical response of
      Si NC-based SLs. 

PMID- 25872564
TI  - Sudden hearing loss due to oxaliplatin use in a patient with colon cancer.
AB  - Oxaliplatin is used to treat advanced colorectal cancer. Platinum-containing
      chemotherapeutic agents are known to be ototoxic. However, ototoxicity is rare
      with newer generation platinum-derived agents, such as oxaliplatin. This case
      report presents a rare case of sudden unilateral sensorineural hearing loss
      following intravenous (IV) infusion of oxaliplatin in a 64-year-old woman with
      advanced colon cancer. The hearing loss was severe and did not respond to
      treatment. To the best of our knowledge, this is the fifth reported case of
      oxaliplatin ototoxicity. Although oxaliplatin ototoxicity is rare, physicians
      must be aware of this important adverse effect, and an audiometric evaluation
      must be performed when necessary. Patients treated with oxaliplatin should be
      followed closely for early signs and symptoms of hearing loss, and if hearing
      loss is detected, treatment should be stopped immediately. 

PMID- 25872563
TI  - Sustained Aeration of Infant Lungs (SAIL) trial: study protocol for a randomized
      controlled trial.
AB  - BACKGROUND: Extremely preterm infants require assistance recruiting the lung to
      establish a functional residual capacity after birth. Sustained inflation (SI)
      combined with positive end expiratory pressure (PEEP) may be a superior method of
      aerating the lung compared with intermittent positive pressure ventilation (IPPV)
      with PEEP in extremely preterm infants. The Sustained Aeration of Infant Lungs
      (SAIL) trial was designed to study this question. METHODS/DESIGN: This multisite
      prospective randomized controlled unblinded trial will recruit 600 infants of 23
      to 26 weeks gestational age who require respiratory support at birth. Infants in
      both arms will be treated with PEEP 5 to 7 cm H2O throughout the resuscitation.
      The study intervention consists of performing an initial SI (20 cm H20 for 15
      seconds) followed by a second SI (25 cm H2O for 15 seconds), and then PEEP with
      or without IPPV, as needed. The control group will be treated with initial IPPV
      with PEEP. The primary outcome is the combined endpoint of bronchopulmonary
      dysplasia or death at 36 weeks post-menstrual age. TRIAL REGISTRATION:
      www.clinicaltrials.gov , Trial identifier NCT02139800 , Registered 13 May 2014.

PMID- 25872565
TI  - Effectiveness of rotavirus vaccines, licensed but not funded, against rotavirus
      hospitalizations in the Valencia Region, Spain.
AB  - BACKGROUND: Although rotavirus vaccines have been licensed in Spain for over 8
      years, they are not funded by its public health systems. The analysis of their
      effectiveness in the Valencia Region could better inform decisions about
      potential inclusion in the official immunization schedule. Our aim was to assess
      the effectiveness of Rotarix(r) (RV1) and RotaTeq(r) (RV5) against rotavirus
      hospitalizations. METHODS: We conducted a retrospective cohort study using the
      region's health care databases, among resident children aged <3 years covered by
      the National Health System, during January 2007-June 2012. We compared two
      cohorts of vaccinated children: the first included children who received at least
      one dose of a rotavirus vaccine, and the second included children who were not
      vaccinated with rotavirus vaccines but received at least one dose of a
      pneumococcal vaccine, another licensed but non-funded vaccine. The main outcome
      was rotavirus hospitalization, either laboratory-confirmed (confirmed) or
      codified as rotavirus (probable). Rotavirus vaccine effectiveness (RVE) by
      vaccine brand was assessed using Cox proportional hazards models. RESULTS: The
      study included 78,281 rotavirus and 96,643 pneumococcal vaccinees. Adjusted RVE
      against probable or confirmed rotavirus hospitalizations was 86% (95% CI: 78-91%)
      and 88% (95% CI: 81-92%) for a complete series of RV1 and RV5 respectively.
      CONCLUSIONS: Both rotavirus vaccines were over 85% effective against rotavirus
      hospitalization among young children. The high effectiveness shown argues in
      favor of their inclusion in the official schedule. Additional information on
      rotavirus vaccine safety, duration of protection, and benefit-risk will also be
      needed to inform such deliberations.

PMID- 25872566
TI  - Exploring open innovation with a patient focus in drug discovery: an evolving
      paradigm of patient engagement.
AB  - It is suggested in this article that patient engagement should occur further
      upstream during the drug discovery stage. 'Lead patients', namely those patients
      who are proactive with respect to their health, possess knowledge of their
      disease and resulting symptoms. They are also well informed about the
      conventional as well as non-conventional treatments for disease management; and
      so can provide a nuanced perspective to drug design. Understanding how patients
      view the management of their diseases and how they view the use of conventional
      versus non-conventional interventions is of imperative importance to researchers.
      Indeed, this can provide insight into how conventional treatments might be
      designed from the outset to encourage compliance and positive health outcomes.
      Consequently, a continuum of lead patient engagement is employed that focuses on
      drug discovery processes ranging from participative, informative to collaborative
      engagement. This article looks at a variety of open innovation models that are
      currently employed across this engagement spectrum. It is no longer sufficient
      for industry stakeholders to consider conventional therapies as the only
      mechanisms being sought after by patients. Without patient engagement, the
      industry risks being re-prioritized in terms of its role in the patient journey
      towards not only recovery of health, but also sustained health and wellness
      before disease onset. 

PMID- 25872567
TI  - Combining curcumin (C3-complex, Sabinsa) with standard care FOLFOX chemotherapy
      in patients with inoperable colorectal cancer (CUFOX): study protocol for a
      randomised control trial.
AB  - BACKGROUND: The need for low toxicity adjuncts to standard care chemotherapy in
      inoperable colorectal cancer, with potential to improve outcomes and decrease the
      side-effect burden, is well recognised. Addition of the low toxicity diet-derived
      agent, curcumin (the active ingredient of turmeric), to standard oxaliplatin
      based therapy has shown promise in numerous pre-clinical studies. METHODS/DESIGN:
      This study is the first to combine daily oral curcumin with standard care FOLFOX
      based (5-fluorouracil, folinic acid and oxaliplatin) chemotherapy in colorectal
      cancer patients with inoperable liver metastases: the CUFOX trial. CUFOX
      comprises a Phase 1 dose-escalation study (3 + 3 + 3 design) to determine an
      acceptable target dose of curcumin with which to safely proceed to a Phase IIa
      open-labelled randomised controlled trial. Thirty three participants with
      histological or cytological confirmation of inoperable colorectal cancer will
      then be randomised to oxaliplatin-based chemotherapy with the addition of daily
      oral curcumin at the target dose determined in Phase I, or to standard care
      oxaliplatin-based chemotherapy alone (recruiting at a ratio of 2:1). DISCUSSION:
      Primary outcome measures will be the determination of a target dose which is both
      safe and tolerable for long-term administration to individuals in receipt of
      first-line oxaliplatin-based chemotherapy for inoperable colorectal cancer.
      Secondary outcome measures will include observation of any changes in neuropathic
      side-effects of chemotherapy, improvement to progression-free or overall survival
      and identification of putative efficacy biomarkers in plasma. The results will be
      disseminated via presentation at national and international conferences, via
      publication in appropriate peer-reviewed journals and via the Cancer Research
      UK/Department of Health Experimental Cancer Medicine Centre Network. This trial
      has full ethical and institutional approval, and commenced recruitment in
      February 2012. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT01490996 , registered
      7(th) December 2011), European Drug Regulating Authorities (EudraCT 2011-002289
      19, registered 13(th) May 2011), UKCRN ID#10672.

PMID- 25872568
TI  - Acylglycerol kinase promotes the proliferation and cell cycle progression of oral
      squamous cell carcinoma.
AB  - Cell proliferation is a major underlying cause of mortality amongst patients with
      oral squamous cell carcinoma (OSCC); however, the underlying mechanisms have
      remained to be elucidated. Acylglycerol kinase (AGK) is a multisubstrate lipid
      kinase, which is known to be associated with the progression of various types of
      human cancer. The present study aimed to investigate the role of AGK in cell
      proliferation and cell cycle progression in OSCC. The expression levels of AGK
      were detected in cancerous and adjacent normal tissue samples from four patients
      with OSCC undergoing surgical resection, and in OSCC cell lines, using the
      polymerase chain reaction (PCR) and western blot analysis. The effects of AGK on
      the proliferation and cell cycle progression of OSCC cells were assessed using a
      short hairpin RNA lentivirus or expressed-plasmid transfection. In addition, the
      expression levels of cyclin D1 and p21, as well as cell proliferation- and cell
      cycle-associated proteins were detected by PCR and western blotting. The results
      of the present study demonstrated that the expression levels of AGK were
      significantly higher in the cancerous tissues and OSCC cell lines, compared with
      the adjacent normal tissues and control cells, respectively. Furthermore, MTT and
      colony formation assays, in addition to flow cytometric analysis were conducted,
      in order to assess the role of AGK in cell proliferation and cell cycle
      progression. The cell proliferation and cell cycle progression of an established
      OSCC cell line were demonstrated to be decreased following AGK knockdown, and
      enhanced by AGK overexpression in vitro. Aberrant AGK expression in OSCC was
      shown to be associated with cell proliferation and cell cycle progression. The
      results of the present study provide evidence that AGK may promote cell
      proliferation and cell cycle progression in OSCC.

PMID- 25872569
TI  - The German version of the Camberwell Assessment of Need for the Elderly (CANE):
      evaluation of content validity and adaptation to the German-speaking context.
AB  - BACKGROUND: The Camberwell Assessment of Need for the Elderly (CANE) was
      developed for the assessment of physical-, psychological-, and environment
      related needs in the elderly. The aim of this study was to revise and adapt the
      German version of the CANE with regard to the content validity of the instrument.
      METHODS: Following a multistage approach, face-to-face interviews using the CANE,
      an expert survey and a multidisciplinary consensus conference were conducted in
      order to evaluate the frequency and relevance of met and unmet needs in the
      German elderly population, and to modify the content of the CANE for the German
      speaking countries. RESULTS: In Germany, unmet physical needs including physical
      health, medication, eyesight/hearing/communication, mobility/falls, self-care,
      and continence were found to have top priority closely followed by social needs
      (company, intimate relationships, daytime activities, information, and
      abuse/neglect). Psychological needs were the lowest ranked care category.
      Experts' proposals for the improvement of the German version of the CANE were
      collected. All findings were discussed and integrated in the multidisciplinary
      consensus conference with the result of a revised and adapted CANE that is
      applicable in the German-speaking context. CONCLUSIONS: The provision of an
      adapted and improved German version of the CANE may substantially contribute to a
      comprehensive and valid assessment of needs in the elderly population. The
      results of this study represent an important basis for comprehensive needs
      assessment in the elderly in the theoretical and practical field of healthcare
      and health services research.

PMID- 25872571
TI  - Genotype-Associated Arginase 1 Expression in Rat Peritoneal Macrophages Induced
      by Toxoplasma gondii.
AB  - Toxoplasma gondii induces polarization of mouse macrophages, including both
      classically activated macrophages (M1) and alternatively activated macrophages
      (M2) in a genotype-related manner. Here we present a novel result that the Wh6
      strain with type Chinese 1, which is predominantly prevalent in China, induces
      Arg1 expression in a STAT6-dependent manner in primary rat peritoneal macrophages
      as compared to the PRU stain with type II, which elicited a high expression of
      Arg1 in a C/EBPbeta-dependent manner. In addition, dexamethasone inhibited Arg1
      expression in rat macrophages in both treatments. Our data suggest that Arg1
      expression, which is abundant in polarized M2 cells, is associated with
      strain/genotype differences from different pathways. 

PMID- 25872570
TI  - Immune Function and Muscle Adaptations to Resistance exercise in Older Adults:
      Study Protocol for a Randomized Controlled Trial of a Nutritional Supplement.
AB  - BACKGROUND: Immune function may influence the ability of older adults to maintain
      or improve muscle mass, strength, and function during aging. Thus, nutritional
      supplementation that supports the immune system could complement resistance
      exercise as an intervention for age-associated muscle loss. The current study
      will determine the relationship between immune function and exercise training
      outcomes for older adults who consume a nutritional supplement or placebo during
      resistance training and post-training follow-up. The supplement was chosen due to
      evidence suggesting its ingredients [arginine (Arg), glutamine (Gln), and beta
      hydroxy beta-methylbutyrate (HMB)] can improve immune function, promote muscle
      growth, and counteract muscle loss. METHODS/DESIGN: Veterans (age 60 to 80 yrs, N
      = 50) of the United States military will participate in a randomized double-blind
      placebo-controlled trial of consumption of a nutritional supplement or placebo
      during completion of three study objectives: 1) determine if 2 weeks of
      supplementation improve immune function measured as the response to vaccination
      and systemic and cellular responses to acute resistance exercise; 2) determine if
      supplementation during 36 sessions of resistance training boosts gains in muscle
      size, strength, and function; and 3) determine if continued supplementation for
      26 weeks post-training promotes retention of training-induced gains in muscle
      size, strength, and function. Analyses of the results for these objectives will
      determine the relationship between immune function and the training outcomes.
      Participants will undergo nine blood draws and five muscle (vastus lateralis)
      biopsies so that the effects of the supplement on immune function and the
      systemic and cellular responses to exercise can be measured. DISCUSSION: Exercise
      has known effects on immune function. However, the study will attempt to modulate
      immune function using a nutritional supplement and determine the effects on
      training outcomes. The study will also examine post-training benefit retention,
      an important issue for older adults, usually omitted from exercise studies. The
      study will potentially advance our understanding of the mechanisms of muscle gain
      and loss in older adults, but more importantly, a nutritional intervention will
      be evaluated as a complement to exercise for supporting muscle health during
      aging. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02261961,
      registration date 10 June 2014, recruitment active.

PMID- 25872572
TI  - Hypoxia-induced miR-181b enhances angiogenesis of retinoblastoma cells by
      targeting PDCD10 and GATA6.
AB  - Previous findings showed that miR-181b is upregulated under hypoxic conditions in
      retinoblastoma cells. Since hypoxia is a common feature of retinoblastoma that
      affects tumor progression as well as tumor therapy, in the present study, we
      investigated the regulatory mechanism of miR-181b under hypoxic conditions, and
      examined the role of miR-181b in retinoblastoma responses to hypoxia
      (chemoresistance and angiogenesis) and possible downstream genes. The level of
      hypoxia-inducible factor-1alpha (HIF-1alpha) and miR-181b was detected to examine
      the link between them. Tube formation and cell cytotoxicity assays were used to
      clarify the effects of miR-181b on hypoxic responses of retinoblastoma cells.
      Bioinformatics analysis was performed to predict potential targets of miR-181b
      and western blotting was used to verify these targets. The results showed a
      significantly increased expression of HIF-1alpha in hypoxia-treated
      retinoblastoma cells. Downregulation of HIF-1alpha using a small-interfering RNA
      (siRNA) knockdown technology did not decrease the expression of miR-181b. Through
      gain- and loss-of-function studies, miR-181b was demonstrated to significantly
      stimulate the ability of capillary tube formation of endothelial cells.
      Programmed cell death-10 (PDCD10) and GATA binding protein 6 (GATA6) were
      identified as the target genes of miR-181b. To the best of our knowledge, results
      of the present study provide the first evidence that miR-181b was upregulated by
      hypoxia in retinoblastoma in an HIF-1alpha-independent manner. miR-181b increased
      tumor angiogenesis of retinoblastoma cells. Additionally, miR-181b exerts its
      angiogenic function, at least in part, by inhibiting PDCD10 and GATA6. Thus, it
      is a new potentially useful therapeutic target for retinoblastoma.

PMID- 25872573
TI  - Ischemic preconditioning protects neurons from damage and maintains the
      immunoreactivity of kynurenic acid in the gerbil hippocampal CA1 region following
      transient cerebral ischemia.
AB  - Pyramidal neurons in region I of hippocampus proper (CA1) are particularly
      vulnerable to excitotoxic processes following transient forebrain ischemia.
      Kynurenic acid (KYNA) is a small molecule derived from tryptophan when this amino
      acid is metabolized through the kynurenine pathway. In the present study, we
      examined the effects of ischemic preconditioning (IPC) on the immunoreactivity
      and protein levels of KYNA following 5 min of transient forebrain ischemia in
      gerbils. The animals were randomly assigned to 4 groups (sham-operated group,
      ischemia-operated group, IPC + sham-operated group and IPC + ischemia-operated
      group). IPC was induced by subjecting the gerbils to 2 min of ischemia followed
      by 1 day of recovery. In the ischemia-operated group, we observed a significant
      loss of pyramidal neurons in the CA1 stratum pyramidale (SP) at 5 days post
      ischemia; however, in the IPC + ischemia-operated group, the pyramidal neurons
      were well protected. KYNA immunoreactivity in the SP of the ischemia-operated
      group was significantly altered following ischemia-reperfusion and was very low 5
      days following ischemia-reperfusion. In the IPC + ischemia-operated group,
      however, KYNA immunoreactivity was constitutively detected in the SP of the CA1
      region after the ischemic insult. We also found that the alteration pattern of
      the KYNA protein level in the CA1 region following ischemia was generally similar
      to the immunohistochemical changes observed. In brief, our findings demonstrated
      that IPC maintained and even increased KYNA immunoreactivity in the SP of the CA1
      region following ischemia-reperfusion. The data from the present study thus
      indicate that the enhancement of KYNA expression by IPC may be necessary for
      neuronal survival following transient ischemic injury.

PMID- 25872574
TI  - Prospective evaluation of postoperative penile rehabilitation: penile
      length/girth maintenance 1 year following Coloplast Titan inflatable penile
      prosthesis.
AB  - INTRODUCTION: The most prevalent long-term complaint after successful inflatable
      penile prosthesis (IPP) surgery is reduction of penile length. The purpose of
      this study was to evaluate penile measurements in patients whose implantation
      experience included the aggressive new length measurement technique (NLMT)
      coupled with postoperative IPP rehabilitation (daily inflation) of the implant
      for 1 year. Moreover, we aimed to document objective data concerning dimensional
      changes of the phallus over time. Postoperative IPP rehabilitation has been
      discussed and presented at meetings, but no multi-institutional prospective data
      have been published. AIM: Our goal was to assess results using the Coloplast
      Titan IPP, with NLMT, and postoperative rehabilitation. METHODS: After IRB
      approval, we conducted a prospective, three-center study of 40 patients who
      underwent IPP placement, with NLMT for end organ failure erectile dysfunction
      with the Coloplast Titan IPP. The patient was instructed to inflate daily for 6
      months and then inflate maximally for 1-2 hours daily for 6-12 months. Fifteen
      penile measurements were taken before and immediately after surgery and at follow
      up visits. MAIN OUTCOME MEASURE: Penile length measurements after implantation
      compared with 12 months postimplantation. RESULTS: Penile measurement changes
      were statistically significantly improved at 12 months as compared with
      immediately postoperative and at 6 months. A total of 64.5% of subjects were
      satisfied with their length at 1 year, and 74.2% had perceived penile length that
      was longer (29%) or the same (45.2%) as prior to the surgery; 61.3% and 16.1% of
      subjects had increased and unchanged satisfaction, respectively, with penile
      length as compared with prior to IPP surgery. All but two subjects (93.4%) were
      satisfied with the overall function and dimensions of their IPP. CONCLUSION: This
      study suggests using the Coloplast Titan IPP with aggressive cylinder sizing, and
      a postoperative penile rehabilitation inflation protocol may help optimize
      patient satisfaction and erectile penile measurements.

PMID- 25872576
TI  - Nickel oxide particles catalyze photochemical hydrogen evolution from water-
      nanoscaling promotes p-type character and minority carrier extraction.
AB  - Nickel(II) oxide (NiO) is an important wide gap p-type semiconductor used as a
      hole transport material for dye sensitized solar cells and as a water oxidation
      electrocatalyst. Here we demonstrate that nanocrystals of the material have
      increased p-type character and improved photocatalytic activity for hydrogen
      evolution from water in the presence of methanol as sacrificial electron donor.
      NiO nanocrystals were synthesized by hydrolysis of Ni(II) nitrate under
      hydrothermal conditions followed by calcination in air. The crystals have the
      rock salt structure type and adopt a plate-like morphology (50-90 nm * 10-15 nm).
      Diffuse reflectance absorbance spectra indicate a band gap of 3.45 eV, similar to
      bulk NiO. Photoelectrochemical measurements were performed at neutral pH with
      methylviologen as electron acceptor, revealing photo-onset potentials (Fermi
      energies) of 0.2 and 0.05 eV (NHE) for nanoscale and bulk NiO, respectively. Nano
      NiO and NiO-Pt composites obtained by photodepositon of H2PtCl6 catalyze hydrogen
      evolution from aqueous methanol at rates of 0.8 and 4.5 MUmol H2 h(-1),
      respectively, compared to 0.5 and 2.1 MUmol H2 h(-1) for bulk-NiO and NiO-Pt (20
      mg of catalyst, 300 W Xe lamp). Surface photovoltage spectroscopy of NiO and NiO
      Pt films on Au substrates indicate a metal Pt-NiO junction with 30 mV
      photovoltage that promotes carrier separation. The increased photocatalytic and
      photoelectrochemical performance of nano-NiO is due to improved minority carrier
      extraction and increased p-type character, as deduced from Mott-Schottky plots,
      optical absorbance, and X-ray photoelectron spectroscopy data. 

PMID- 25872575
TI  - Dopamine physiology in the basal ganglia of male zebra finches during social
      stimulation.
AB  - Accumulating evidence suggests that dopamine (DA) is involved in altering neural
      activity and gene expression in a zebra finch cortical-basal ganglia circuit
      specialized for singing, upon the shift between solitary singing and singing as a
      part of courtship. Our objective here was to sample changes in the extracellular
      concentrations of DA in Area X of adult and juvenile birds, to test the
      hypothesis that DA levels would change similarly during presentation of a
      socially salient stimulus in both age groups. We used microdialysis to sample the
      extracellular milieu of Area X in awake, behaving adult and juvenile male zebra
      finches, and analysed the dialysate using high-performance liquid chromatography
      coupled with electrochemical detection. The extracellular levels of DA in Area X
      increased significantly during both female presentation to adult males and tutor
      presentation to juvenile males. DA levels were not correlated with the time spent
      singing. We also reverse-dialysed Area X with pharmacologic agents that act
      either on DA systems directly or on norepinephrine, and found that all of these
      agents significantly increased DA levels (3- to 10-fold) in Area X. These
      findings suggest that changes in extracellular DA levels can be stimulated
      similarly by very different social contexts (courtship and interaction with
      tutor), and influenced potently by dopaminergic and noradrenergic drugs. These
      results raise the possibility that the arousal level or attentional state of the
      subject (rather than singing behavior) is the common feature eliciting changes in
      extracellular DA concentration. 

PMID- 25872577
TI  - Aligned carbon nanotube film enables thermally induced state transformations in
      layered polymeric materials.
AB  - The energy losses and geometric constraints associated with conventional curing
      techniques of polymeric systems motivate the study of a highly scalable out-of
      oven curing method using a nanostructured resistive heater comprised of aligned
      carbon nanotubes (A-CNT). The experimental results indicate that, when compared
      to conventional oven based techniques, the use of an "out-of-oven" A-CNT
      integrated heater leads to orders of magnitude reductions in the energy required
      to process polymeric layered structures such as composites. Integration of this
      technology into structural systems enables the in situ curing of large-scale
      polymeric systems at high efficiencies, while adding sensing and control
      capabilities. 

PMID- 25872579
TI  - Dopant incorporation site in sodium cobaltate's host lattice: a critical factor
      for thermoelectric performance.
AB  - NaxCoO2 that comprises alternating Na and CoO layers has exotic magnetic and
      thermoelectric properties that could favorably be manipulated by adding dopants
      or varying Na concentration. In this work, we investigated the structural and
      electronic properties of Sr and Sb doped NaxCoO2 (x = 0.50, 0.625, 0.75 and
      0.875) through comprehensive density functional calculations. We found that Sr
      dopants always occupy a site in the Na layer while Sb dopants always substitute a
      Co ion in the host lattice regardless of Na concentration. This conclusion
      withstood when either generalized gradient approximation (GGA) or GGA + U method
      was used. By residing on the Na layer, Sr dopants create charge and mass inertia
      against the liquid-like Na layer and, therefore, improve the crystallinity and
      decrease the electrical resistivity through better carrier mobility. On the other
      hand, by substituting Co ions, Sb dopants reduce the electrical conductivity and
      therefore decrease the Seebeck coefficient. 

PMID- 25872580
TI  - MicroRNA-155 modulates the proliferation of vascular smooth muscle cells by
      targeting endothelial nitric oxide synthase.
AB  - A variety of microRNAs (miRNAs) have been reported to be significantly be
      involved in the regulation of vascular smooth muscle cell (VSMC) proliferation,
      which is an essential process for the formation of atherosclerotic plaque. The
      objective of the present study was to explore the role of microRNA-155 (miR-155)
      in the regulation of VSMC growth and migration. A total of 12 atherosclerotic
      plaque samples and 9 control samples were collected, and the expression levels of
      miR-155/endothelial nitric oxide synthase (eNOS) were determined in those samples
      by RT-qPCR and western blot analysis. The results revealed that the relative
      expression levels of miR-155 in the atherosclerotic plaque samples were
      significantly upregulated compared with those in the normal control samples. We
      further found eNOS to be an effective target of miR-155 in the VSMCs by
      luciferase assay, which was confirmed by the observation that VSMCs transfected
      with miR-155 mimics exhibited a significantly lower protein expression level of
      eNOS. We also demonstrated that the exogenous overexpression of miR-155
      significantly enhanced cell proliferation by inhibiting apoptosis in human aortic
      SMCs (HASMCs), and it also promoted the migratory ability of the cells. In
      conclusion, our data demonstrate that miR-155 is significantly upregulated in
      atherosclerotic plaque, functioning to accelerate the proliferation and migration
      of VSMCs by targeting eNOS.

PMID- 25872578
TI  - Open-label, randomized, comparative, phase III study on effects of reducing
      steroid use in combination with Palonosetron.
AB  - The purpose of this study is to compare the efficacy of a single administration
      of dexamethasone (DEX) on day 1 against DEX administration on days 1-3 in
      combination with palonosetron (PALO), a second-generation 5-HT3 receptor
      antagonist, for chemotherapy-induced nausea and vomiting (CINV) in non
      anthracycline and cyclophosphamide (AC) moderately-emetogenic chemotherapy (MEC).
      This phase III trial was conducted with a multi-center, randomized, open-label,
      non-inferiority design. Patients who received non-AC MEC as an initial
      chemotherapy were randomly assigned to either a group administered PALO (0.75 mg,
      i.v.) and DEX (9.9 mg, i.v.) prior to chemotherapy (study treatment group), or a
      group administered additional DEX (8 mg, i.v. or p.o.) on days 2-3 (control
      group). The primary endpoint was complete response (CR) rate. The CR rate
      difference was estimated by logistic regression with allocation factors as
      covariates. The non-inferiority margin was set at -15% (study treatment group -
      control group). From April 2011 to March 2013, 305 patients who received non-AC
      MEC were randomly allocated to one of two study groups. Overall, the CR rate was
      66.2% in the study treatment group (N = 151) and 63.6% in the control group (N =
      154). PALO plus DEX day 1 was non-inferior to PALO plus DEX days 1-3 (difference,
      2.5%; 95% confidence interval [CI]: -7.8%-12.8%; P-value for non-inferiority test
      = 0.0004). There were no differences between the two groups in terms of complete
      control rate (64.9 vs 61.7%) and total control rate (49.7% vs 47.4%). Anti-emetic
      DEX administration on days 2-3 may be eliminated when used in combination with
      PALO in patients receiving non-AC MEC. 

PMID- 25872582
TI  - Food science needs for 2050.

PMID- 25872584
TI  - Assessment of the Stoichiometry of Multicomponent Crystals Using Only X-ray
      Powder Diffraction Data.
AB  - Knowledge of the unit cell volume of a crystalline form and the expected space
      filling requirements of an API molecule can be used to determine if a crystalline
      material is likely to be multicomponent, such as a solvate, hydrate, salt, or a
      co-crystal. The unit cell information can be readily accessed from powder
      diffraction data alone utilizing powder indexing methodology. If the unit cell
      has additional space not likely attributable to the API entity, then there is
      either a void or another component within the crystal lattice. This "leftover"
      space can be used to determine the likely stoichiometry of the additional
      component. A simple approach for calculating the expected required volume for a
      given molecule within a crystal using an atom based additive approach will be
      discussed. Coupling this estimation with the actual unit cell volumes and space
      group information obtained from powder indexing allows for the rapid evaluation
      of the likely stoichiometry of multicomponent crystals using diffraction data
      alone. This approach is particularly useful for the early assessment of new
      phases during salt, co-crystal, and polymorph screening, and also for the
      characterization of stable and unstable solvates. 

PMID- 25872585
TI  - Normative data for the Strengths and Difficulties Questionnaire for young
      children in Australia.
AB  - AIM: The aim of this study was to report normative data for the parent-reported
      Strengths and Difficulties Questionnaire (SDQ) from a large population cohort of
      young children aged 4-6 years from Victoria, Australia, to establish age- and sex
      specific cut-off values for future use, and to determine the scale reliability of
      the SDQ for children aged 4-6 years. METHODS: Parents of children (n = 53 372)
      entering their first year of school in Victoria in 2010 completed a survey via a
      15-page School Entrant Health Questionnaire reporting on the physical and
      emotional well-being of their child (including the SDQ), use of child health and
      other support services, and a range of socio-demographic variables. Reliability
      was assessed and norms generated. Appropriate cut-off values for each SDQ scale
      and total difficulties scale were generated for each age group separately for
      each sex. RESULTS: The five scales of the SDQ and total difficulties scale
      generally had acceptable internal reliability. Mean SDQ scale scores differed for
      both sex and age, although only a narrow age range is examined in this study. Cut
      off values were marginally higher for girls (lower for prosocial) and generally
      increased with age. CONCLUSIONS: This study has utilised a large Australian
      population sample of children to generate age- and sex-specific cut-off values
      that define SDQ scores as 'normal', 'borderline' or 'abnormal' for Australian
      children aged 4-6 years.

PMID- 25872586
TI  - The novel inhibitor BRM270 downregulates tumorigenesis by suppression of NF
      kappaB signaling cascade in MDR-induced stem like cancer-initiating cells.
AB  - The nuclear factor kappaB (NF-kappaB) and interleukin-6 (IL-6) contribute to
      multidrug resistance (MDR) in tumor chemotherapy. The essential phenomenon of
      oncogenic activation of NF-kappaB in cancer-initiating cells showing MDR
      resulting from increased IL-6 expression is still unclear. Cancer stem cells
      (CSCs) have been the objective of intensive study. The aim of this study was to
      investigate the selective and potential efficacy of BRM270 against stem-like
      cancer-initiating cells (SLCICs) via the molecular mechanisms of its anticancer
      effects. Co-regulation of NF-kappaB and Cdk6 might be new arena to mitigate
      tumorigenesis. In the present study phyto-drug based approach provides a new
      avenue in understanding the amelioration and regulatory mechanisms in CSCs. In
      the present study, an in vivo tumor metastasis model of osteosarcoma was
      established by injecting Cal72 and SaOS-2 SLCICs into the right lower flank of
      nude mice. Later the development of tumor was analyzed by LICOR Biosciences
      (Pearl image analyzer). Significant suppression of activation of NF-kappaB and
      LPS-induced gene expression and apoptosis by BRM270 was confirmed by FACS,
      western blotting and qPCR. Further, both p65 and Cdk6 were significantly (P<0.05)
      overexpressed in BRM270 non-treated Cal72 SLCICs compared to treated group.
      BRM270 directly dephosphorylated RelA and selectively inhibited NF-kappaB
      transcriptional activity, resulting in decreased expression of interleukin-6, a
      cytokine implicated in cancer metastasis. BRM270-mediated cell shrinkage,
      pyknosis, karyorrhexis and programmed cell death (PCD) were observed by Hoechst
      33342 staining while flow cytometry analysis showed significant (P<0.05) decrease
      in cell population from G0-G1 phases. These findings suggest that activation of
      the oncogenic Cdk6-NF-kappaB pathway, resulting from increased IL-6 expression,
      plays a central role in CD133 expressing SLCICs augmented MDR and neoplasia. This
      study proposes targeting of NF-kappaB, and Cdk6 with IL-6 as potential targets
      for PCD and treatment of chemotherapeutic resistance of CSCs to design novel
      therapies for their elimination.

PMID- 25872587
TI  - Luminescent Coordination Glass: Remarkable Morphological Strategy for Assembled
      Eu(III) Complexes.
AB  - Syntheses of novel luminescent Eu(III) coordination glasses 1 ([Eu(hfa)3(o
      dpeb)]2), 2 ([Eu(hfa)3(m-dpeb)]3), and 3 ([Eu(hfa)3(p-dpeb)]n) are reported. They
      are composed of Eu(III) ions, hexafluoroacetylacetonato (hfa) ligands, and unique
      bent-angled phosphine oxide (o-, m-, p-dpeb) ligands with ethynyl groups. Their
      coordination structures and glass formability are dependent on the regiochemistry
      of substitution in regard to the internal benzene core. Single-crystal X-ray
      analyses and DFT calculation reveals dinuclear, trinuclear, and polymer
      structures for Eu(III) coordination glasses 1, 2, and 3, respectively. Those
      compounds show characteristic glass-transition (Tg = 25-96  degrees C) and strong
      luminescence properties (PhiLn = 72-94%). 

PMID- 25872589
TI  - Treatment outcomes for eosinophilic esophagitis in children with esophageal
      atresia.
AB  - Eosinophilic esophagitis (EoE) has been reported to be more prevalent in patients
      with esophageal atresia/tracheoesophageal fistula (EA-TEF). To date, there is
      limited data on the management of EoE in this group of patients. The aim of this
      study is to evaluate the treatment outcomes of EoE in children with EA-TEF. A
      retrospective chart review was performed on all EA-TEF children who were
      diagnosed with and treated for EoE between January 2000 and September 2013 at the
      Sydney Children's Hospital. Data collected included details of the patient's
      treatment, post-treatment endoscopy, symptoms and nutrition. Twenty patients were
      included in the study. Median age at diagnosis was 26 months (8-103 months), and
      median time from diagnosis to last follow-up was 23 months (2-132 months).
      Patients were treated with budesonide slurry, swallowed fluticasone, elimination
      diet alone or in combination. All patients were on proton pump inhibitors at time
      of diagnosis of EoE which was continued. Six out of seven patients who had
      furrowing/exudate in endoscopy at diagnosis had complete resolution at a median
      follow-up period of 26 months (P = 0.031). Median peak intraepithelial eosinophil
      count reduced significantly from 30/high-powered field (HPF) (19-80/HPF) to 8/HPF
      (0-85/HPF) (median time for improvement = 24 months) (P = 0.015). There was a
      significant reduction in symptoms of dysphagia and reflux post-treatment (P <
      0.001). Prevalence of strictures significantly decreased (P = 0.016), as did need
      for dilatations (P = 0.004). In four out of six patients with gastrostomies at
      baseline, the feeding improved on treatment of EoE and the gastrostomy could be
      closed. There was also a nonsignificant trend towards improvement in weight and
      height 'z scores' of the patients. Treatment of EoE in children with EA-TEF was
      found to significantly reduce intraepithelial eosinophil count, symptoms,
      strictures and need for dilatations. 

PMID- 25872588
TI  - The role of a structured exercise training program on cardiac structure and
      function after acute myocardial infarction: study protocol for a randomized
      controlled trial.
AB  - BACKGROUND: Exercise training is effective in improving functional capacity and
      quality of life in patients with coronary artery disease, but its effects on left
      ventricular systolic and diastolic function are controversial. Diastolic
      dysfunction is a major determinant of adverse outcome after myocardial infarction
      and, contrary to systolic function, no therapy or intervention has proved to
      significantly improve diastolic function. Data from animal studies and from
      patients with diastolic heart failure has suggested that exercise training can
      have a positive effect on diastolic function parameters. This trial aims to
      evaluate if a structured exercise training program can improve resting left
      ventricular diastolic and systolic function in patients who have had an acute
      myocardial infarction. METHODS/DESIGN: This is a phase II, prospective,
      randomized, open-label, blinded-endpoint trial that will include at least 96
      consecutive patients who have had an acute myocardial infarction one month
      previously. Patients will be randomized (1:1) to an exercise training program or
      a control group, receiving standard of care. At enrolment, and at the end of the
      follow-up period, patients will be submitted to an echocardiography (with
      detailed assessment of diastolic and systolic function using recent consensus
      guidelines), cardiopulmonary exercise testing, an anthropometric assessment,
      blood testing, and clinical evaluation. Patients randomized to the intervention
      group will be submitted to an eight-week outpatient exercise program, combining
      endurance and resistance training, for three sessions per week. The primary
      endpoint will be the change in lateral E' velocity immediately after the eight
      week exercise training program. Secondary endpoints will include other
      echocardiographic parameters of left ventricular diastolic and systolic function,
      cardiac structure, metabolic and inflammation biomarkers (high-sensitivity C
      reactive protein and pro-BNP), functional capacity (peak oxygen consumption and
      anaerobic threshold) and anthropometric measurements. DISCUSSION: New strategies
      that can improve left ventricular diastolic function are clinically needed. This
      will be the first trial to evaluate, in patients who have had an acute myocardial
      infarction, the effects of a structured program of exercise training on diastolic
      and systolic function, assessed by novel echocardiographic parameters. TRIAL
      REGISTRATION: Registered with ClinicalTrials.gov (reference: NCT02224495 ) on 21
      August 2014.

PMID- 25872591
TI  - Progress and Milestones in Scientific Communication--a 150 years perspective.

PMID- 25872590
TI  - Laser therapy for onychomycosis in patients with diabetes at risk for foot
      complications: study protocol for a randomized, double-blind, controlled trial
      (LASER-1).
AB  - BACKGROUND: In a sham-controlled double-blind trial, we aim to establish the
      efficacy and safety of the local application of laser therapy in patients with
      diabetes, onychomycosis and risk factors for diabetes-related foot complications.
      Onychomycosis leads to thickened and distorted nails, which in turn lead to
      increased local pressure. The combination of onychomycosis and neuropathy or
      peripheral arterial disease (PAD) increases the risk of developing diabetes
      related foot complications. Usual care for high-risk patients with diabetes and
      onychomycosis is completely symptomatic with frequent shaving and clipping of the
      nails. No effective curative local therapies exist, and systemic agents are often
      withheld due to concerns for side effects and interactions. METHODS/DESIGN: The
      primary aim is to evaluate the efficacy of four sessions of Nd:YAG 1064 nM laser
      application on the one-year clinical and microbiological cure rate in a
      randomized, double-blind, sham-controlled design with blinded outcome assessment.
      Mandatory inclusion criteria are diagnosis of diabetes, risk factors for
      developing foot ulcers defined as a modified Simm's classification score 1 or 2
      and either neuropathy or PAD. A total of 64 patients are randomized to
      intervention or sham treatment performed by a podiatrist. DISCUSSION: This study
      will be the first double-blind study that investigates the effects of local laser
      therapy on onychomycosis, specifically performed in patients with diabetes with
      additional risk factors for foot complications. TRIAL REGISTRATION: Clinical
      trials.gov as NCT01996995 , first received 22 November 2013.

PMID- 25872592
TI  - Propranolol represses infantile hemangioma cell growth through the beta2
      adrenergic receptor in a HIF-1alpha-dependent manner.
AB  - Propranolol, as a non-selective blocker of the beta-adrenergic receptor (AR), is
      utilised as the first-line treatment for infantile hemangiomas. However, the
      underlying mechanism remains poorly understood. The present study was designed to
      investigate the molecular basis of propranolol on the regression of infantile
      hemangiomas using a proliferating infantile hemangioma-derived endothelial cell
      line. In infantile hemangioma patients, we found that propranolol significantly
      decreased the expression levels of the hypoxia inducible factor (HIF)-1alpha in
      serum and urine, as well as in hemangioma tissues. In vitro analysis revealed
      that propranolol reduces the expression of HIF-1alpha in hemangioma cells in a
      dose- and time-dependent manner, mainly by acting on beta2-AR. Interestingly, it
      was observed that overexpression of HIF-1alpha apparently abrogated the
      inhibitory effects of propranolol on vascular endothelial growth factor (VEGF)
      expression and cell growth. Our data further demonstrated that propranolol
      inhibited the signal transducer and activator of transcription 3 (STAT3), a
      critical oncogenic signaling molecule, and the anti-apoptotic protein Bcl-2.
      Additionally, overexpression of HIF-1alpha significantly reversed the inhibitory
      effects of propranolol on STAT3 signaling. In a mouse xenograft hemangioma model,
      overexpression of HIF-1alpha significantly attenuated the therapeutic effects of
      propranolol and inhibited propranolol-induced hemangioma cell apoptosis.
      Moreover, the protein levels of VEGF, phosphorylated STAT3, total STAT3 and Bcl-2
      were significantly upregulated by HIF-1alpha overexpression in propranolol
      treated nude mice bearing hemangiomas. Collectively, our data provide evidence
      that propranolol may regress infantile hemangiomas by suppressing VEGF and STAT3
      signaling pathways in an HIF-1alpha-dependent manner.

PMID- 25872594
TI  - Expression of CYP2E1 and CYP2U1 proteins in amygdala and prefrontal cortex:
      influence of alcoholism and smoking.
AB  - BACKGROUND: The tissue-specific expression of cytochrome P450 enzymes (CYP, P450)
      in the human brain may influence the therapeutic response to, and side effects
      of, neuroactive drugs including alcohol. However, the distribution of many P450s,
      especially poorly characterized CYP2 forms, within specific regions of the brain
      remains obscure, partly due to the paucity of available tissue and difficulty in
      discriminating between related P450s with available antibodies. METHODS: In this
      study, we analyzed the expression of CYP2A6, CYP2B6, CYP2D6, CYP2E1, CYP2J2,
      CYP2S1, CYP2U1, and CYP2W1 proteins in human prefrontal cortex (PFC) and amygdala
      (AMG) by immunoblotting with antibodies for which the P450 form specificity had
      been enhanced by affinity purification. These brain regions were selected as they
      mediate the addictive effects of cigarette smoking and alcohol consumption,
      substances known to modulate P450 expression in other tissues. PFC and AMG
      samples from alcoholic smokers, alcoholic nonsmokers, nonalcoholic smokers, and
      nonalcoholic nonsmokers were studied to assess the effect of alcohol use and
      smoking on the expression of these proteins. RESULTS: Of the P450s studied,
      CYP2E1 and CYP2U1 were expressed in all samples analyzed (n = 26 and 22 for
      CYP2E1 and CYP2U1, respectively), and elevated in alcoholics. CYP2U1 expression
      was also slightly increased in smokers. Expression of both P450s was increased in
      AMG compared to PFC of the same individuals. CONCLUSIONS: This is the first
      report of CYP2E1 and CYP2U1 protein expression in human AMG. Our results suggest
      that CYP2U1 expression may be modulated by alcohol and tobacco, with potential
      consequent effects on the metabolism of drugs and endogenous chemicals by this
      enzyme.

PMID- 25872593
TI  - Alcoholic liver disease: the gut microbiome and liver cross talk.
AB  - Alcoholic liver disease (ALD) is a leading cause of morbidity and mortality
      worldwide. Alcoholic fatty liver disease can progress to steatohepatitis,
      alcoholic hepatitis, fibrosis, and cirrhosis. Patients with alcohol abuse show
      quantitative and qualitative changes in the composition of the intestinal
      microbiome. Furthermore, patients with ALD have increased intestinal permeability
      and elevated systemic levels of gut-derived microbial products. Maintaining
      eubiosis, stabilizing the mucosal gut barrier, or preventing cellular responses
      to microbial products protect from experimental ALD. Therefore, intestinal
      dysbiosis and pathological bacterial translocation appear fundamental for the
      pathogenesis of ALD. This review highlights causes for intestinal dysbiosis and
      pathological bacterial translocation, their relationship, and consequences for
      ALD. We also discuss how the liver affects the intestinal microbiota. 

PMID- 25872595
TI  - Brief report: genetics of alcoholic cirrhosis-GenomALC multinational study.
AB  - BACKGROUND: The risk of alcohol-related liver cirrhosis increases with increasing
      alcohol consumption, but many people with very high intake escape from liver
      disease. We postulate that susceptibility to alcoholic cirrhosis has a complex
      genetic component and propose that this can be dissected through a large and
      sufficiently powered genomewide association study (GWAS). METHODS: The GenomALC
      Consortium comprises researchers from Australia, France, Germany, Switzerland,
      United Kingdom, and United States, with a joint aim of exploring the genetic and
      genomic basis of alcoholic cirrhosis. For this National Institutes of
      Health/National Institute on Alcohol Abuse and Alcoholism funded study, we are
      recruiting high-risk drinkers who are either cases (with alcoholic cirrhosis) or
      controls (drinking comparable amounts over similar time, but free of significant
      liver disease). Extensive phenotypic data are obtained using semistructured
      interviews and patient records, and blood samples are collected. RESULTS: We have
      successfully recruited 859 participants including 538 matched case-control
      samples as of September 2014, using study-specific inclusion-exclusion criteria
      and data collection protocols. Of these, 580 are cases (442 men and 138 women)
      and 279 are controls (205 men and 74 women). Duration of excessive drinking was
      slightly greater in cases than controls and was significantly less in women than
      men. Cases had significantly lower lifetime alcohol intake than controls. Both
      cases and controls had a high prevalence of reported parental alcohol problems,
      but cases were significantly more likely to report that a father with alcohol
      problems had died from liver disease (odds ratio 2.53, 95% confidence interval
      1.31 to 4.87, p = 0.0055). CONCLUSIONS: Recruitment of participants for a GWAS of
      alcoholic cirrhosis has proved feasible across countries with multiple sites.
      Affected patients often consume less alcohol than unaffected ones, emphasizing
      the existence of individual vulnerability factors. Cases are more likely to
      report liver disease in a father with alcohol problems than controls, consistent
      with a potential genetic component to the risk of alcoholic cirrhosis.

PMID- 25872596
TI  - Simultaneous versus concurrent use of alcohol and cannabis in the National
      Alcohol Survey.
AB  - BACKGROUND: Cannabis is the most commonly used drug among those who drink, yet no
      study has directly compared those who use cannabis and alcohol simultaneously
      versus concurrently (i.e., separately) in the adult general population. Here, we
      assess differences in demographics, alcohol-related social consequences, harms to
      self, and drunk driving across simultaneous, concurrent, and alcohol-only using
      groups. METHODS: Secondary analyses of the 2005 and 2010 National Alcohol Survey
      (N = 8,626; 4,522 female, 4,104 male), a Computer Assisted Telephone Interview
      survey of individuals aged 18 and older from all 50 states and DC. Blacks and
      Hispanics are over-sampled. Data were collected using list-assisted Random Digit
      Dialing. Multinomial and multivariable logistic regressions were used for
      analyses. RESULTS: The prevalence of simultaneous use was almost twice as high as
      concurrent use, implying that individuals who use both cannabis and alcohol tend
      to use them at the same time. Furthermore, simultaneous use was associated with
      increased frequency and quantity of alcohol use. Simultaneous use was also the
      most detrimental: compared to alcohol only, simultaneous use approximately
      doubled the odds of drunk driving, social consequences, and harms to self. The
      magnitudes of differences in problems remained when comparing drunk driving among
      simultaneous users to concurrent users. CONCLUSIONS: The overall set of results
      is particularly important to bear in mind when studying and/or treating problems
      among alcohol/cannabis co-users because they demonstrate that in the general
      population, co-users are a heterogeneous group who experience different
      likelihoods of problems relative to co-use patterns.

PMID- 25872597
TI  - Alcohol cues impair learning inhibitory signals in beer drinkers.
AB  - BACKGROUND: Models of drug addiction emphasize the reciprocal influence of
      incentive-motivational properties of drug-related cues and poor impulse control
      resulting in drug use. Recent studies have shown that alcohol-related cues can
      impair response inhibition. What is unknown is whether these cues also disrupt
      learning of inhibitory associations. METHODS: Participants performed a
      conditioned inhibition (CI) task and were required to learn that a neutral image
      was a conditioned inhibitor when presented in the context of either an alcohol
      image intended to draw their attention away from the to-be-trained inhibitor, or
      a control condition in which the alcohol image was absent. After training,
      subjects in each condition rated the likelihood that the neutral image would
      signal the outcome. Eye tracking was used to verify that attention to the neutral
      image was in fact reduced when the alcohol image was present. RESULTS: Compared
      with controls those trained in the alcohol image condition reported a greater
      likelihood that the presence of the inhibitor would be followed by the outcome
      and thus were less able to acquire CI. Measures of eye tracking verified that
      attention to the alcohol cue was associated with this maladaptive behavior.
      CONCLUSIONS: When alcohol cues are present, there is a reduced ability to learn
      that such information is irrelevant to an outcome, and this impairs ones' ability
      to inhibit perseveration of a response. This has implications for persistence of
      a drinking episode.

PMID- 25872598
TI  - Social anxiety and peer helping in adolescent addiction treatment.
AB  - BACKGROUND: The developmental need to fit in may lead to higher alcohol and other
      drug use among socially anxious youths which exacerbates the drink/trouble cycle.
      In treatment, youths with social anxiety disorder (SAD) may avoid participating
      in therapeutic activities with risk of negative peer appraisal. Peer-helping is a
      low-intensity, social activity in the 12-step program associated with greater
      abstinence among treatment-seeking adults. This study examined the influence of
      SAD on clinical severity at intake, peer-helping during treatment, and outcomes
      in a large sample of adolescents court-referred to residential treatment.
      METHODS: Adolescents (N = 195; 52% female, 30% Black) aged 14 to 18 were
      prospectively assessed at treatment admission, treatment discharge, and 6 months
      after treatment discharge. Data were collected using rater-administered
      assessments, youth reports, clinician reports, medical charts, and electronic
      court records. The influence of SAD on peer-helping and outcomes was examined
      using hierarchical linear regression and event history methods. RESULTS: Forty
      two percent of youths reported a persistent fear of being humiliated or
      scrutinized in social situations, and 15% met current diagnostic criteria for
      SAD. SAD onset preceded initial use for two-thirds of youths with SAD and
      substance dependency. SAD youths presented for treatment with greater clinical
      severity in terms of earlier age of first use (p < 0.01), greater lifetime use of
      heroin and polysubstance use (p < 0.05), incarceration history (p < 0.01), and
      lifetime trauma (p < 0.001). Twelve-step participation patterns during treatment
      did not differ between youths with and without SAD except for peer-helping, which
      was associated with reduced risk of relapse (p < 0.01) and incarceration (p <
      0.05) in the 6 months posttreatment. CONCLUSIONS: This study found evidence of an
      association between SAD and earlier age of first use, greater lifetime use of
      heroin, incarceration history, and lifetime trauma. SAD was associated with
      higher service participation during treatment, which was associated with reduced
      risk of relapse and incarceration in the 6 months posttreatment. Findings
      indicate the benefits of service participation for juveniles with SAD which
      provides a nonjudgmental, task-focused venue for developing sober networks in the
      transition back into the community.

PMID- 25872599
TI  - Brief motivational interventions for college student drinking may not be as
      powerful as we think: an individual participant-level data meta-analysis.
AB  - BACKGROUND: For over 2 decades, brief motivational interventions (BMIs) have been
      implemented on college campuses to reduce heavy drinking and related negative
      consequences. Such interventions include in-person motivational interviews (MIs),
      often incorporating personalized feedback (PF), and stand-alone PF interventions
      delivered via mail, computer, or the Web. Both narrative and meta-analytic
      reviews using aggregate data from published studies suggest at least short-term
      efficacy of BMIs, although overall effect sizes have been small. METHODS: This
      study was an individual participant-level data (IPD) meta-analysis of 17
      randomized clinical trials evaluating BMIs. Unlike typical meta-analysis based on
      summary data, IPD meta-analysis allows for an analysis that correctly
      accommodates the sampling, sample characteristics, and distributions of the
      pooled data. In particular, highly skewed distributions with many zeroes are
      typical for drinking outcomes, but have not been adequately accounted for in
      existing studies. Data are from Project INTEGRATE, one of the largest IPD meta
      analysis projects to date in alcohol intervention research, representing 6,713
      individuals each with 2 to 5 repeated measures up to 12 months postbaseline.
      RESULTS: We used Bayesian multilevel over dispersed Poisson hurdle models to
      estimate intervention effects on drinks per week and peak drinking, and Gaussian
      models for alcohol problems. Estimates of overall intervention effects were very
      small and not statistically significant for any of the outcomes. We further
      conducted post hoc comparisons of 3 intervention types (individual MI with PF, PF
      only, and group MI) versus control. There was a small, statistically significant
      reduction in alcohol problems among participants who received an individual MI
      with PF. Short-term and long-term results were similar. CONCLUSIONS: This study
      questions the efficacy and magnitude of effects of BMIs for college drinking
      prevention and intervention and suggests a need for the development of more
      effective intervention strategies.

PMID- 25872600
TI  - Incidence and Risk Factors for Tuberculosis After Liver Transplantation in an
      Endemic Area: A Nationwide Population-Based Matched Cohort Study.
AB  - Morbidity and mortality from tuberculosis (TB) are high in Taiwan. We conducted a
      nationwide population-based matched cohort study using data retrieved from the
      Taiwan's National Health Insurance Research Database to determine the impact of
      TB after liver transplantation (LT). During 2000-2011, we identified 3202 liver
      transplant recipients and selected subjects from the general population matched
      for age, sex, and comorbidities on the same index date of recognition of LT with
      a 1:10 ratio. The data were analyzed using Cox proportional hazards models.
      Compared to the matched cohort, liver transplant patients had a higher risk for
      TB (adjusted HR 2.25, 95% CI 1.65-3.05, p < 0.001), and those with TB showed
      higher mortality (HR 2.27, 95% CI 1.30-3.97, p = 0.004). Old age (HR 2.64, 95% CI
      1.25-5.54, p = 0.011) and mammalian target of rapamycin inhibitors (mTORis) (HR
      3.09, 95% CI 1.68-5.69, p < 0.001) were significant risk factors for TB in LT;
      mTORis were also associated with mortality after adjusting for confounders (HR
      2.13, 95% CI 1.73-2.62, p < 0.001). Therefore, regular surveillance of TB and
      treatment of latent TB infection in high-risk patients after LT are important,
      especially in TB-endemic areas. 

PMID- 25872601
TI  - The effect of terminal groups of viologens on their binding behaviors and
      thermodynamics upon complexation with sulfonated calixarenes.
AB  - The binding modes, inclusion abilities, and thermodynamic parameters for the
      intermolecular complexation of p-sulfonatocalix[4]arene (SC4A), p
      sulfonatocalix[5]arene (SC5A), and p-sulfonatothiacalix[4]arene (STC4A), with
      methyl viologen (MV(2+)), ethyl viologen (EV(2+)), propyl viologen (PV(2+)),
      butyl viologen (BV(2+)), and benzyl viologen (BnV(2+)), were systematically
      investigated by NMR spectroscopy, molecular mechanics calculation, and
      microcalorimetry in neutral aqueous solutions. The obtained results show that all
      the sulfonated calixarene hosts can form stable inclusion complexes with viologen
      guests driven by much favorable enthalpy changes. All the viologen guests are
      encapsulated into the smaller SC4A cavity in their axial orientation. The larger
      SC5A cavity can accommodate all the viologen guests at its upper-rim midsection
      in the latitudinal orientation. The binding modes of more flexible STC4A with the
      smaller MV(2+) and EV(2+) guests are similar to those of SC5A with the two
      guests, while the binding modes of STC4A with the larger PV(2+) and BV(2+) guests
      are similar to those of SC4A with the two guests. The host selectivity for all
      the investigated viologen guests is the same: SC5A > SC4A > STC4A. The magnitude
      of the host selectivity is associated with the size of the guest. Moreover, the
      thermodynamic origin of the host selectivity for these viologen guests can be
      explained well by host-guest binding modes. 

PMID- 25872602
TI  - [Anaphylactic reaction to intravenous glucocorticoid in a patient with chronic
      obstructive pulmonary disease].
AB  - Serious anaphylactic reactions to systemic glucocorticoids are rare and have
      previously mainly been reported in patients with asthma or aspirin allergy. We
      report a case of severe anaphylactic reaction to an intravenous (IV)
      glucocorticoid in a patient with chronic obstructive pulmonary disease. A 61-year
      old male developed severe bronchospasm within seconds after IV injection of
      methylprednisolone sodium succinate. The condition was immediately treated with
      adrenaline and the patient recovered quickly. Clinicians should be aware of the
      possibility of anaphylactic reactions to glucocorticoids. 

PMID- 25872603
TI  - [Breast carcinoma metastasis to the gastrointestinal tract and tumour-to-tumour
      metastasis to renal cell carcinoma].
AB  - Breast carcinoma metastasis to the gastrointestinal tract and tumour-to-tumour
      metastasis is rare. We describe a case of a 71-year-old woman with previous
      breast cancer presenting with dyspepsia, nausea and weight-loss. Biopsies from
      the pylorus revealed what appeared to be a gastric carcinoma. A CT scan showed
      large kidney mass and biopsies revealed clear cell renal cell carcinoma with
      areas of poorly differentiated adenocarcinoma. Subsequent immunohistochemical
      analysis revealed the presence of breast carcinoma in both locations. 

PMID- 25872604
TI  - [IgG4-related disease is a rare differential diagnosis of malignant and
      autoimmune diseases].
AB  - Immunoglobulin G4-related disease (IgG4-RD) is an inflammatory and fibrotic
      disease with the potential to produce diffuse enlargement, massforming lesions or
      stenoses in a wide range of organs. Elevation of serum IgG4 concentration and
      high levels of IgG4-positive cells in the inflamed tissue are common
      denominators. Type 1 autoimmune pancreatitis is one of the main manifestations,
      and its recognition preceded the definition of IgG4-RD as a novel clinical
      entity. The aetiology, pathophysiology, epidemiology and clinical long-term
      outcome of IgG4-RD are not fully elucidated. Steroids are effective in most
      patients, sometimes combined with other antiinflammatory drugs. 

PMID- 25872605
TI  - [Fatal outcome for a patient in treatment with dabigatran suffering a
      subtrochanteric femoral fracture].
AB  - An 82-year-old woman in treatment with the thrombin inhibitor dabigatran
      etexilate (a new oral anticoagulant (NOAC)) was admitted with a subtrochanteric
      femoral fracture and surgery was initiated 15 hours after admittance. She had a
      blood loss of 6,000 ml and died the next morning from multi-organ failure. In
      2013 1.8% of hip fracture patients in Funen received NOACs. Surgery is
      recommended within 24 hours for hip fracture patients to reduce mortality, but
      patients in treatment with NOACs should wait at least 48 hours before major
      surgery. Care should be taken when prescribing NOACs to patients with high risk
      of falling. 

PMID- 25872606
TI  - [Infrequent arrhythmia episodes diagnosed by a smartphone-based event recorder].
AB  - Smartphone-based ECG monitor devices are a new promising tool for rhythm
      detection in patients with palpitations. We present a case where a young patient
      with infrequent arrhythmia episodes was diagnosed with atrial fibrillation using
      this novel smartphone-based event recorder. 

PMID- 25872607
TI  - [Inverted papilloma of the middle ear can cause pain, intermittent facial palsy
      and hearing loss].
AB  - Inverted papilloma of the middle ear is extremely rare and so far only 25 cases
      have been published in medical literature. It is a benign, rapidly growing tumour
      with higher incidence of malignancy and recurrence compared with sinonasal
      papillomas. The aetiology remains unknown. Typical clinical presentation includes
      hearing loss, otorrhoea and otalgia. Treatment is surgical radical resection of
      the lesion and radiotherapy in selected cases. Long-term follow-up, including MRI
      is recommended, due to the risk of recurrence and malignant degeneration. 

PMID- 25872608
TI  - [The effect of lifestyle modification on chronic constipation].
AB  - First-line treatment of constipation includes dietary fibre, fluid and exercise.
      The evidence for these recommendations is, however, scarce. Increased intake of
      fibre will reduce colonic transit time and improve the frequency and consistency
      of stools in 50% of patients. Bloating and flatulence are common side effects to
      highly fermentable fibres. Daily intake of 2 l of water enhances the positive
      effects of fibre and 30 min. exercise per day also alleviates symptoms.
      Conservative treatment is usually insufficient and should be supplemented with
      laxatives or motility enhancing drugs. 

PMID- 25872609
TI  - The impact of epidemics of vaccine-preventable disease on vaccine uptake: lessons
      from the 2011-2012 US pertussis epidemic.
AB  - Conventional wisdom suggests that if there is a vaccine that is effective in
      preventing a disease, vaccine uptake will increase when the disease risk is high.
      Recent evidence, however, suggests that this may not always be the case. In a
      study we conducted in Washington State, we found no population-level increase in
      pertussis vaccination of infants during a pertussis epidemic. In this paper, we
      aim to review what is known about the history of vaccine uptake during epidemics
      of vaccine-preventable disease, the challenges facing public health campaigns
      responding to these epidemics, and how the effect of a vaccine-preventable
      disease epidemic on vaccine uptake can be studied. 

PMID- 25872611
TI  - Oxidative N-heterocyclic carbene catalyzed stereoselective annulation of simple
      aldehydes and 5-alkenyl thiazolones.
AB  - A highly diastereoselective annulation of simple aldehydes and 5-alkenyl
      thiazolones, via oxidative NHC catalysis has been developed. This strategy
      provides facile access to a diverse library of functionalized chiral thiazolo
      pyrones. Aerobic oxygen can also be applied as a secondary oxidant to avoid the
      use of stoichiometric organic or inorganic oxidants. 

PMID- 25872610
TI  - The renal protective effect of angiotensin receptor blockers depends on intra
      individual response variation in multiple risk markers.
AB  - AIMS: Angiotensin receptor blockers (ARBs) are renoprotective and targeted to
      blood pressure. However, ARBs have multiple other (off-target) effects which may
      affect renal outcome. It is unknown whether on-target and off-target effects are
      congruent within individuals. If not, this variation in short term effects may
      have important implications for the prediction of individual long term renal
      outcomes. Our aim was to assess intra-individual variability in multiple
      parameters in response to ARBs in type 2 diabetes. METHODS: Changes in systolic
      blood pressure (SBP), albuminuria, potassium, haemoglobin, cholesterol and uric
      acid after 6 months of losartan treatment were assessed in the RENAAL database.
      Improvement in predictive performance of renal outcomes (ESRD or doubling serum
      creatinine) for each individual using ARB-induced changes in all risk markers was
      assessed by the relative integrative discrimination index (RIDI). RESULTS: SBP
      response showed high variability (mean -5.7 mmHg, 5(th) to 95(th) percentile 
      36.5 to +24.0 mmHg) between individuals. Changes in off-target parameters also
      showed high variability between individuals. No congruency was observed between
      responses to losartan in multiple parameters within individuals. Using individual
      responses in all risk markers significantly improved renal risk prediction (RIDI
      30.4%, P < 0.01) compared with using only SBP changes. Results were successfully
      replicated in two independent trials with irbesartan, IDNT and IRMA-2.
      CONCLUSIONS: In this post hoc analysis we showed that ARBs have multiple off
      target effects which vary between and within individuals. Combining all ARB
      induced responses beyond SBP provides a more accurate prediction of who will
      benefit from ARB therapy. Prospective trials are required to validate these
      findings.

PMID- 25872613
TI  - Spin glasses: redux: an updated experimental/materials survey.
AB  - This article reviews the 40+ year old spin-glass field and one of its earliest
      model interpretations as a spin density wave. Our description is from an
      experimental phenomenological point of view with emphasis on new spin glass
      materials and their relation to topical problems and strongly correlated
      materials in condensed matter physics. We first simply define a spin glass (SG),
      give its basic ingredients and explain how the spin glasses enter into the
      statistical mechanics of classical phase transitions. We then consider the four
      basic experimental properties to solidly characterize canonical spin glass
      behavior and introduce the early theories and models. Here the spin density wave
      (SDW) concept is used to explain the difference between a short-range SDW, i.e. a
      SG and, in contrast, a long-range SDW, i.e. a conventional magnetic phase
      transition. We continue with the present state of SG, its massive computer
      simulations and recent proposals of chiral glasses and quantum SG. We then
      collect and mention the various SG 'spin-off's'. A major section uncovers the
      fashionable unconventional materials that display SG-like freezing and glassy
      ground states, such as (high temperature) superconductors, heavy fermions,
      intermetallics and Heuslers, pyrochlor and spinels, oxides and chalogenides and
      exotics, e.g. quasicrystals. Some conclusions and future directions complete the
      review. 

PMID- 25872614
TI  - Revealing the binding mode between respiratory syncytial virus fusion protein and
      benzimidazole-based inhibitors.
AB  - Human respiratory syncytial virus (HRSV) is a major respiratory pathogen in
      newborn infants and young children and can also be a threat to some elderly and
      high-risk adults with chronic pulmonary disease and the severely
      immunocompromised. The RSV fusion (RSVF) protein has been an attractive target
      for vaccine and drug development. Experimental results indicate a series of
      benzimidazole-based inhibitors which target RSVF protein to inhibit the viral
      entry of RSV. To reveal the binding mode between these inhibitors and RSVF
      protein, molecular docking and molecular dynamics simulations were used to
      investigate the interactions between the inhibitors and the core domain of RSVF
      protein. MD results suggest that the active molecules have stronger pi-pi
      stacking, cation-pi, and other interactions than less active inhibitors. The
      binding free energy between the active inhibitor and RSVF protein is also found
      to be significantly lower than that of the less active one using MM/GBSA. Then,
      Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity
      Indices Analysis (CoMSIA) methods were used to construct three dimensional
      quantitative structure-activity (3D-QSAR) models. The cross-validated q(2) values
      are found to be 0.821 and 0.795 for CoMFA and CoMSIA, respectively. And the non
      cross-validated r(2) values are 0.973 and 0.961. Ninety-two test set compounds
      validated these models. The results suggest that these models are robust with
      good prediction abilities. Furthermore, these models reveal possible methods to
      improve the bioactivity of inhibitors. 

PMID- 25872612
TI  - Effectiveness of dual-task functional power training for preventing falls in
      older people: study protocol for a cluster randomised controlled trial.
AB  - BACKGROUND: Falls are a major public health concern with at least one third of
      people aged 65 years and over falling at least once per year, and half of these
      will fall repeatedly, which can lead to injury, pain, loss of function and
      independence, reduced quality of life and even death. Although the causes of
      falls are varied and complex, the age-related loss in muscle power has emerged as
      a useful predictor of disability and falls in older people. In this population,
      the requirements to produce explosive and rapid movements often occurs whilst
      simultaneously performing other attention-demanding cognitive or motor tasks,
      such as walking while talking or carrying an object. The primary aim of this
      study is to determine whether dual-task functional power training (DT-FPT) can
      reduce the rate of falls in community-dwelling older people. METHODS/DESIGN: The
      study design is an 18-month cluster randomised controlled trial in which 280
      adults aged >=65 years residing in retirement villages, who are at increased risk
      of falling, will be randomly allocated to: 1) an exercise programme involving DT
      FPT, or 2) a usual care control group. The intervention is divided into 3
      distinct phases: 6 months of supervised DT-FPT, a 6-month 'step down' maintenance
      programme, and a 6-month follow-up. The primary outcome will be the number of
      falls after 6, 12 and 18 months. Secondary outcomes will include: lower extremity
      muscle power and strength, grip strength, functional assessments of gait,
      reaction time and dynamic balance under single- and dual-task conditions,
      activities of daily living, quality of life, cognitive function and falls-related
      self-efficacy. We will also evaluate the cost-effectiveness of the programme for
      preventing falls. DISCUSSION: The study offers a novel approach that may guide
      the development and implementation of future community-based falls prevention
      programmes that specifically focus on optimising muscle power and dual-task
      performance to reduce falls risk under 'real life' conditions in older adults. In
      addition, the 'step down' programme will provide new information about the
      efficacy of a less intensive maintenance programme for reducing the risk of falls
      over an extended period. TRIAL REGISTRATION: Australian New Zealand Clinical
      Trials Registry: ACTRN12613001161718 . Date registered 23 October 2013.

PMID- 25872615
TI  - Competitive excited-state single or double proton transfer mechanisms for bis-2,5
      (2-benzoxazolyl)-hydroquinone and its derivatives.
AB  - The excited state intramolecular proton transfer (ESIPT) mechanisms of 2-(2
      hydroxyphenyl)benzoxazole (HBO), bis-2,5-(2-benzoxazolyl)-hydroquinone (BBHQ) and
      2,5-bis(5'-tert-butyl-benzoxazol-2'-yl)hydroquinone (DHBO) have been investigated
      using time-dependent density functional theory (TDDFT). The calculated vertical
      excitation energies based on the TDDFT method reproduced the experimental
      absorption and emission spectra well. Three kinds of stable structures were found
      on the S1 state potential energy surface (PES). A new ESIPT mechanism that
      differs from the one proposed previously (Mordzinski et al., Chem. Phys. Lett.,
      1983, 101, 291. and Lim et al., J. Am. Chem. Soc., 2006, 128, 14542.) is
      proposed. The new mechanism includes the possibility of simultaneous double
      proton transfer, or successive single transfers, in addition to the accepted
      single proton transfer mechanism. Hydrogen bond strengthening in the excited
      state was based on primary bond lengths, angles, IR vibrational spectra and
      hydrogen bond energy. Intramolecular charge transfer based on the frontier
      molecular orbitals (MOs) also supports the proposed mechanism of the ESIPT
      reaction. To further elucidate the proposed mechanism, reduced dimensionality
      PESs of the S0 and S1 states were constructed by keeping the O-H distance fixed
      at a series of values. The potential barrier heights among the local minima on
      the S1 surface imply competitive single and double proton transfer branches in
      the mechanism. Based on the new ESIPT mechanism, the observed fluorescence
      quenching can be satisfactorily explained. 

PMID- 25872616
TI  - Septic abortion caused by Campylobacter jejuni bacteraemia.
AB  - A 20-year-old female patient, 14 weeks pregnant, was admitted to hospital with
      anamnestic and clinical features of acute pyelonephritis. Clinical signs of
      septic abortion developed and after obstetric examination the therapy was changed
      to ampicillin, gentamicin and clindamycin. Campylobacter jejuni was isolated from
      blood cultures. Pathohistological findings confirmed diagnosis of purulent
      chorioamnionitis. After 2 weeks of ciprofloxacin administration the patient fully
      recovered. Campylobacter jejuni was not isolated from stool culture and no signs
      of acute enteritis were registered during the illness. Invasive forms of
      Campylobacter disease without enteritis are not unusual in immunocompromised
      hosts but they are restricted to C. fetus rather than C. jejuni isolates. 

PMID- 25872618
TI  - A Cu(2+) specific metallohydrogel: preparation, multi-responsiveness and
      pillar[5]arene-induced morphology transformation.
AB  - A Cu(2+) specific metallohydrogel was constructed from a terpyridine-based low
      molecular weight ligand. The metallohydrogel showed multi-responsive gel-to-sol
      transitions and pillar[5]arene-induced nanofiber-to-vesicle transformation at the
      nanoscale. 

PMID- 25872617
TI  - Uncontrolled Web-based administration of surveys on factual health-related
      knowledge: a randomized study of untimed versus timed quizzing.
AB  - BACKGROUND: Health knowledge and literacy are among the main determinants of
      health. Assessment of these issues via Web-based surveys is growing continuously.
      Research has suggested that approximately one-fifth of respondents submit cribbed
      answers, or cheat, on factual knowledge items, which may lead to measurement
      error. However, little is known about methods of discouraging cheating in Web
      based surveys on health knowledge. OBJECTIVE: This study aimed at exploring the
      usefulness of imposing a survey time limit to prevent help-seeking and cheating.
      METHODS: On the basis of sample size estimation, 94 undergraduate students were
      randomly assigned in a 1:1 ratio to complete a Web-based survey on nutrition
      knowledge, with or without a time limit of 15 minutes (30 seconds per item); the
      topic of nutrition was chosen because of its particular relevance to public
      health. The questionnaire consisted of two parts. The first was the validated
      consumer-oriented nutrition knowledge scale (CoNKS) consisting of 20 true/false
      items; the second was an ad hoc questionnaire (AHQ) containing 10 questions that
      would be very difficult for people without health care qualifications to answer
      correctly. It therefore aimed at measuring cribbing and not nutrition knowledge.
      AHQ items were somewhat encyclopedic and amenable to Web searching, while CoNKS
      items had more complex wording, so that simple copying/pasting of a question in a
      search string would not produce an immediate correct answer. RESULTS: A total of
      72 of the 94 subjects started the survey. Dropout rates were similar in both
      groups (11%, 4/35 and 14%, 5/37 in the untimed and timed groups, respectively).
      Most participants completed the survey from portable devices, such as mobile
      phones and tablets. To complete the survey, participants in the untimed group
      took a median 2.3 minutes longer than those in the timed group; the effect size
      was small (Cohen's r=.29). Subjects in the untimed group scored significantly
      higher on CoNKS (mean difference of 1.2 points, P=.008) and the effect size was
      medium (Cohen's d=0.67). By contrast, no significant between-group difference in
      AHQ scores was documented. Unexpectedly high AHQ scores were recorded in 23%
      (7/31) and 19% (6/32) untimed and timed respondents, respectively, very probably
      owing to "e-cheating". CONCLUSIONS: Cribbing answers to health knowledge items in
      researcher-uncontrolled conditions is likely to lead to overestimation of
      people's knowledge; this should be considered during the design and
      implementation of Web-based surveys. Setting a time limit alone may not
      completely prevent cheating, as some cheats may be very fast in Web searching.
      More complex and contextualized wording of items and checking for the
      "findability" properties of items before implementing a Web-based health
      knowledge survey may discourage help-seeking, thus reducing measurement error.
      Studies with larger sample sizes and diverse populations are needed to confirm
      our results.

PMID- 25872619
TI  - Attention placebo control in randomized controlled trials of psychosocial
      interventions: theory and practice.
AB  - Attention placebo control (APC) is considered a highly valid control condition
      when conducting trials of social interventions. Unfortunately, an appropriate APC
      condition is rarely used. This letter discusses the tension between
      methodological and ethical requirements of an APC group in psychosocial
      interventions based on our experiences with a randomized controlled efficacy
      study of a parent training program. To prevent negative side effects and high
      drop-out rates, feasible and accepted attention control conditions are discussed.
      The paradigms of placebo research must be adapted to the special challenges of
      psychosocial intervention research. TRIAL REGISTRATION: Clinicaltrials.gov
      NCT02313493 : registered 10 December 2014.

PMID- 25872620
TI  - 14th Annual Meeting of the Safety Pharmacology Society: threading through
      scientific sessions for originality and novelty.
AB  - INTRODUCTION: The Annual Meeting of the Safety Pharmacology (SP) Society is a
      yearly event designed to keep attendees abreast of how to best identify and
      mitigate organ function liabilities of candidate drugs selected for clinical
      assessment. AREAS COVERED: Heart rate (HR) and blood pressure (BP) effects of
      candidate drugs in dogs/monkeys have satisfactory human translation. Mechanism
      designed assays offer opportunities for innovative approaches to identify
      chemotherapeutic-induced peripheral neuropathy (PN). SP has a large array of
      methodologies to determine safety on eye functions. Video-tracking analysis of
      zebrafish swimming behavior accurately profiles drugs for high-level brain
      function liabilities. Available in vitro and in vivo assays can identify, and
      determine physiological and pharmacological mechanisms of, candidate drug-induced
      emesis. Ad hoc Working Groups have already finalized protocols for testing the
      comprehensive in vitro arrhythmia assay (CiPA), an innovative paradigm for
      assessing mechanisms conferring candidate drug proarrhythmic liabilities. EXPERT
      OPINION: The good concordance of non-clinical and clinical Phase I BP and HR
      effects of candidate drugs support the use of dog/monkey models for clinical
      outcome. Drug liabilities (e.g., PN, nausea, vomiting, etc.) affecting non-vital
      organs/systems require the same degree of SP attention given to vital functions
      as they can dramatically reduce patient quality of life.

PMID- 25872622
TI  - Universities!

PMID- 25872621
TI  - Clinical outcome of patients with pancreatic metastases from renal cell cancer.
AB  - BACKGROUND: Renal cell cancer (RCC) is one of the most frequent primary sites for
      metastatic pancreatic tumors although metastatic tumors are rare among pancreatic
      malignant tumors. The purpose of this study is to disclose the characterization
      and treatment outcomes of pancreatic metastases from RCC. METHODS: Of 262
      patients with metastatic RCC treated at our hospital between 1999 and 2013, the
      data of 20 (7.6%) who simultaneously developed or subsequently acquired
      pancreatic metastases were retrospectively reviewed and statistically analyzed.
      RESULTS: The median follow-up period from RCC diagnosis and pancreatic metastases
      was 13.4 years (inter-quartile range: IQR, 7.8-15.5 years) and 3.8 years (IQR,
      2.1-5.5 years), respectively. Median duration from diagnosis of RCC to pancreatic
      metastasis was 7.8 years (IQR, 4.2-12.7 years). During this observation period,
      the estimated median overall survival (OS) time from the diagnosis of RCC to
      death or from pancreatic metastasis to death was not reached. The probability of
      patients surviving after pancreatic metastasis at 1, 3, and 5 years was 100,
      87.7, and 78.9%, respectively. The estimated OS period from the diagnosis of
      metastases to death of the patients with pancreatic metastasis was significantly
      longer than that of the patients with non-pancreatic metastasis (median OS 2.7
      years) (P < 0.0001). Surgical management for pancreatic metastasis was performed
      in 15 patients (75%). When the median follow-up period for these surgeries was
      3.5 years (IQR, 1.9-5.2 years), the estimated median recurrence-free survival was
      1.8 years. For the patients with multiple metastatic sites, molecularly targeted
      therapies were given to six (30%) patients. When the median follow-up period was
      4.1 years (IQR, 3.0-4.4 years), no disease progression was observed. CONCLUSIONS:
      The pancreas is frequently the only metastatic site and metastasis typically
      occurs a long time after nephrectomy. The OS period of these patients is long and
      both surgical and medical treatment resulted in good outcomes.

PMID- 25872623
TI  - Family related factors associated with caries prevalence in the primary dentition
      of five-year-old children.
AB  - BACKGROUND: Habits formed in childhood dictate lifestyle choices made as adults.
      These encompass both oral hygiene and dietary habits which in turn affect dental
      caries status. Children largely acquire these habits from modeling/observing
      parents and other family members. AIM: The purpose of this study was to assess
      the caries status of 5-year-olds, and evaluate associations between dental caries
      and family-related factors. MATERIALS AND METHODS: A cohort of 400 children were
      examined for dental caries using the WHO criteria. Parents were interviewed using
      a self-structured questionnaire to collect data with regard to variables under
      evaluation. STATISTICAL ANALYSIS: Collected data was subjected to descriptive
      analysis using the SPSS 12.0 version. Risk factor association with dental caries
      was investigated using a stepwise logistic regression analysis with P-values <
      0.05 considered significant. RESULTS: Fifty nine percent of children suffered
      from dental caries. Statistically significant risk indicators for a child having
      dmft > 0 were: Mother with low basic education (OR = 1.3), higher number of
      siblings (OR = 1.4), high snacking frequency (OR = 2.0), parental inability to
      control sugar consumption (OR = 1.0) parental laxness about the child's tooth
      brushing (OR = 1.5), parents brushing their own teeth less than twice daily (OR=
      2.0) and unassisted brushing by the child (OR = 1.8). CONCLUSION: It is thus
      mandatory to focus on parents' education level, attitudes and family-structure
      when planning preventive programs for young children.

PMID- 25872624
TI  - Personality and psychological factors: effects on dental beliefs.
AB  - BACKGROUND: Dental treatment can be highly unpleasant for anxious patients.
      Despite all advancements, dental anxiety continues to upset the dentist-patient
      relationship. The psychological factors like individual personality and familial
      and peer influence may alter the dental beliefs of a patient. AIM: A cross
      sectional questionnaire study was conducted among young adolescents to
      investigate the relationship among various psychological factors and the dental
      beliefs of an individual. MATERIALS AND METHODS: A self-administered
      questionnaire was distributed among higher secondary school children, aged 15-17
      years in Udupi district. The dental anxiety of the participants was measured
      using Modified Dental Beliefs scale and the personality traits were assessed
      using the Ten-Item Personality Inventory. Pearson's correlation and chi-square
      analysis were performed among these scales. Independent t-test was performed to
      compare dental anxiety scores with different socio-demographic and psychological
      characteristics. RESULTS: In all 198 students, with a mean age of 16.6 years,
      completed the questionnaire. A majority of the participants had lower MDBS
      scores. The personality traits like Emotional Stability and Openness to New
      Experiences showed a negative correlation with the Dental Belief scores. Apart
      from these, the experience at first dental visit and peer support also affected
      the dental beliefs of the adolescents. CONCLUSION: Various psychological traits
      of adolescents influence their dental anxiety.

PMID- 25872625
TI  - Assessment of the changes in the stress-related salivary cortisol levels to the
      various dental procedures in children.
AB  - BACKGROUND: Fear and pain are the factors producing stress and there is evidence
      that dental fear acquired in childhood may persist to influence adult behavior.
      Dental treatment is often considered as anxiety producing and stressful. AIM: To
      assess the levels of stress displayed by the healthy children undergoing routine
      dental procedures like oral examination, restoration, and extraction by analyzing
      salivary levels of cortisol before, during, and after the procedures. MATERIALS
      AND METHODS: Twenty healthy children aged between 4 and 8 years having their
      first dental visit and requiring at least one restoration and one extraction were
      selected. In each patient, three procedures were carried out: (i) Routine dental
      examination, (ii) restoration, and (iii) extraction. Unstimulated salivary
      samples were collected 10 min before, during the procedure, and 30 min after each
      procedure at three different visits for comparison of cortisol production in
      response to anxiety and stress over time. Total 180 samples were collected to
      determine salivary cortisol levels using UBI-MAGIWEL TM kit and the readings were
      noted. STATISTICAL ANALYSIS USED: Statistical Package for Social Sciences (SPSS)
      software with paired t-test, two independent sample t-tests, and analysis of
      variance (ANOVA) were used to analyze the findings. RESULTS: A correlation
      between salivary cortisol and stress in dental procedure was noticed. Cavity
      preparation is more stressful procedure in children, so alternative methods can
      be used in anxious children. Stress associated with extraction persists to a
      postoperative period. No correlation exists in between Corah's anxiety scale and
      salivary cortisol.

PMID- 25872626
TI  - Predictors of missing data when asking parents about their children's diet based
      on "Oral Health Situation of Iranian Children" Survey.
AB  - BACKGROUND: The predictors of missing data when parents fill out questionnaire
      about their children's diet are not defined. The aim of this study was to
      evaluate predictors which affect unresponsiveness to diet questions based on "
      Oral Health Situation of Iranian Children" Survey carried out in 1998. MATERIALS
      AND METHODS: A dummy variable was created as dependent variable according to
      responding eight questions relating to diet. Then predictors of missing data were
      defined using multivariable logistic regression and classification tree method.
      To evaluate goodness of fit of logistic regression model, sensitivity and
      specificity were assessed. Classification tree analysis was done by Quest growing
      method. Significance level was set at 0.05 in logistic regression analysis.
      OBSERVATIONS AND RESULTS: "Missing data" variable was marked as missing in 616
      (7.2%) of questionnaires. In logistic regression model revealed that, gender,
      mother's education level and father's education level didn't affect "missing
      data" variable (P > 0.05). But, dmf index (OR = 0.94), Area of living (OR =
      0.49), number of children in the family (OR = 1.19), sibling order (OR = 0.85),
      brushing (OR = 0.84) and visiting dentist (OR = 0.59) had statistically
      significant association with dependent variable (P < 0.05). Classification tree
      analysis showed that questionnaires related to children in urban area whose dmf
      index is under 5 and haven't visited dentist are predicted to have missing data
      more than other groups. CONCLUSIONS: Area of living, dmf index, number of
      children in the family, sibling order, brushing and visiting dentist are
      significant variables for predicting the risk of missing data when asking parents
      about their children's diet.

PMID- 25872627
TI  - Clinical and radiographic evaluation of indirect pulp treatment with MTA and
      calcium hydroxide in primary teeth (in-vivo study).
AB  - OBJECTIVES: Clinical and radiographic effects of mineral trioxide aggregate
      (white MTA) and calcium hydroxide (Dycal) in indirect pulp treatment (IPT) of
      primary teeth over a period of 6 months. MATERIALS AND METHODS: A clinical trial
      with sample size of 40 primary molars between the age group of 5-9 years, of
      which, 20 teeth were considered, each for MTA and Dycal. Measurements on the
      digitized radiographs were performed at baseline, third and sixth month, increase
      in dentin was then measured using Corel Draw software. RESULT: Independent t-test
      had indicated that at the end of 3 months and 6 months, a statistically
      significant increase in dentin thickness with both MTA and Dycal (P-value <=
      0.001) was found. Within the MTA group, the thickness of dentin formed was 0.089
      mm +/- 0.031 mm at first 3 months and 0.055 +/- 0.022 mm at the second 3 months,
      (P <= 0.001) evaluated using paired t-test. In the Dycal group, increment in
      dentin deposited was 0.068 mm at the first 3 months and second 3 months, it was
      0.030 mm (P-value <= 0.001). CONCLUSION: Clinically and radiographically, MTA is
      superior to Dycal as a good IPT medicament in primary teeth.

PMID- 25872628
TI  - Dental anomalies of the deciduous dentition among Indian children: a survey from
      Jodhpur, Rajasthan, India.
AB  - BACKGROUND: Anomalies and enamel hypoplasia of deciduous dentition are routinely
      encountered by dental professionals and early detection and careful management of
      such conditions facilitates may help in customary occlusal development.
      OBJECTIVE: The aim of this study was to determine the prevalence of hypodontia,
      microdontia, double teeth, and hyperdontia of deciduous teeth among Indian
      children. MATERIALS AND METHODS: The study group comprised 1,398 children (735
      boys, 633 girls). The children were examined in department of Pedodontics and
      Preventive Dentistry in Jodhpur Dental College General Hospital, Jodhpur,
      Rajasthan, India. Clinical data were collected by single dentist according to
      Kreiborg criteria, which includes double teeth, hypodontia, microdontia, and
      supernumerary teeth. Statistical analysis of the data was performed using the
      descriptive analysis and chi-square test. RESULTS: Dental anomalies were found in
      4% of children. The distribution of dental anomalies were significantly more
      frequent (P = 0.001) in girls (5.8%, n = 38) than in boys (2.7%, n = 18). In
      relation to anomaly frequencies at different ages, significant difference was
      found between 2 and 3 years (P = 0.001). CONCLUSION: Double teeth were the most
      frequently (2.3%) observed anomaly. The other anomalies followed as 0.3%
      supernumerary teeth, 0.6% microdontia, 0.6% hypodontia. Identification of dental
      anomalies at an early age is of great importance as it prevents malocclusions,
      functional and certain psychological problems.

PMID- 25872629
TI  - Comparison of shear bond strength and micro-leakage of three commercially
      available seventh generation bonding agents in primary anterior teeth: an in
      vitro study.
AB  - PURPOSE: The study was conducted with the aim of comparing the shear bond
      strength (SBS) and microleakage of Tetric N-Bond, G-bond, and Xeno V (seventh
      generation dentin adhesives) in primary anterior teeth. MATERIALS AND METHODS:
      For the shear bond strength, 45 teeth were randomly divided in to three groups
      namely group A, B, C (n = 15). Samples were mounted horizontally on acrylic block
      exposing the facial surface and bonded with different adhesives according to
      manufacturer instructions. A split Teflon mold was used to build the composite
      resin cylinder and light cured. Shear bond strength was tested using a universal
      testing machine. The values were statistically analysed. For microleakage,
      another 45 teeth were similarly grouped. Two class V cavities were prepared on
      the labial surface and treated with different dentine bonding agents and restored
      with resin composite (Ivoclar vivadent) A2 shade. The restorations were
      subsequently thermally stressed for 200 cycles and were subjected to dye
      penetration test, followed by sectioning through the center of the restoration
      labiolingually. Each section was examined using stereomicroscope at * 40
      magnification to asses dye penetration at the margins of the restoration.
      RESULTS: The SBS varied between 22.12-23.77 N/mm 2 (P-value = 0.231). The
      microleakage scores varied between 0.6-1.2 (P-value = 0.03; Post-hoc test A vs B
      (0.007)).There was a statistically higher degree of microleakage observed in
      group A when compared to group B. CONCLUSION: Among the three commercially
      available bonding agents, there were no statistically significant differences in
      SBS. G bond had higher microleakage when compared to the others.

PMID- 25872630
TI  - Impact of perinatal oral health care education programme on the knowledge,
      attitude and practice behavior amongst gynaecologists of Vadodara City.
AB  - CONTEXT: Gynecologists the Primary Health Care providers, for pregnant mothers
      bear the unique responsibility to detect and diagnose oral health problems for
      timely and effective interventions. AIM: The aim of the study was to assess the
      impact of Perinatal Oral Health Care (POHC) education program on the knowledge,
      attitude and practice behavior amongst Gynaecologists of Vadodara City. SETTINGS
      AND DESIGN: An analytical cross sectional study was conducted amongst
      Gynecologists practicing in Vadodara city, registered under Indian Medical
      Association (IMA), Baroda, Gujarat. MATERIALS AND METHODS: A validated
      questionnaire survey was conducted to establish a baseline level of knowledge,
      attitude and practice behavior of 46 Gynecologists. After that education and
      awareness regarding POHC to Gynecologists was provided with the help of flip
      charts and resource brochures. To determine the impact of recent provision of
      education and awareness a post-test was conducted. STATISTICAL ANALYSIS USED:
      Data was analyzed by paired t-test using the SPSS Version 20. RESULTS: The
      results after evaluating the data from pretest and posttest showed a mean
      increase of correct answers in knowledge (from 7.304-9.891; P = 0.00), Attitude
      (from 3.978-4.108; P = 0.49) and practice behavior (from 4.130-5.521; P = 0.00)
      in POHC amongst Gynecologists following the education program. CONCLUSIONS: It
      can be concluded that there is a need for provision of education and awareness to
      the primary health care providers which would help in improving pregnant women
      and infant's oral health status along with establishment of dental home.

PMID- 25872631
TI  - Effect of high-molecular-weight component of Cranberry on plaque and salivary
      Streptococcus mutans counts in children: an in vivo study.
AB  - BACKGROUND: Previous investigations showed that a high-molecular-weight,
      nondialyzable material (NDM) from cranberries inhibits the adhesion of a number
      of bacterial species and prevents the coaggregation of many oral bacterial pairs.
      AIM: In the present study, the effect of mouthrinse containing high-molecular
      weight component of cranberry was evaluated on colonization of Streptococcus
      mutans in children and compared it with a control mouthrinse without high
      molecular-weight component on Streptococcus mutans counts. MATERIALS AND METHODS:
      A high-molecular-weight NDM was isolated from cranberry juice concentrate after
      the dialysis of the cranberry concentrate; followed by lyophilization. A
      mouthwash was prepared especially for the study having NDM in the concentration
      of 3 mg/ml. Following 4 weeks of daily usage of cranberry-containing mouthwash by
      the children of an experimental group (n = 20), the Streptococcus mutans counts
      in plaque and saliva were compared with that in control group using placebo
      mouthwash (n = 20) with the help of Dentocult SM strips. RESULTS: There was a
      highlysignificant reduction in Streptococcus mutans counts in saliva and plaque
      of children using mouthwash containing cranberry NDM (P < 0.05) compared to
      control. CONCLUSION: The data suggest that the high-molecular-weight cranberry
      extract in mouthwash has a significant potential in reducing the Streptococcus
      counts in the oral environment.

PMID- 25872632
TI  - The significance of gtf genes in caries expression: a rapid identification of
      Streptococcus mutans from dental plaque of child patients.
AB  - AIM: Rapid phylogenetic and functional gene (gtfB) identification of S. mutans
      from the dental plaque derived from children. MATERIAL AND METHODS: Dental plaque
      collected from fifteen patients of age group 7-12 underwent centrifugation
      followed by genomic DNA extraction for S. mutans. Genomic DNA was processed with
      S. mutans specific primers in suitable PCR condtions for phylogenetic and
      functional gene (gtfB) identification. The yield and results were confirmed by
      agarose gel electrophoresis. RESULTS: 1% agarose gel electrophoresis depicts the
      positive PCR amplification at 1,485 bp when compared with standard 1 kbp
      indicating the presence of S. mutans in the test sample. Another PCR reaction was
      set using gtfB primers specific for S. mutans for functional gene identification.
      1.2% agarose gel electrophoresis was done and a positive amplication was observed
      at 192 bp when compared to 100 bp standards. CONCLUSION: With the advancement in
      molecular biology techniques, PCR based identification and quantification of the
      bacterial load can be done within hours using species-specific primers and DNA
      probes. Thus, this technique may reduce the laboratory time spend in conventional
      culture methods, reduces the possibility of colony identification errors and is
      more sensitive to culture techniques.

PMID- 25872633
TI  - Appropriate electrode placement site of electric pulp tester for the premolars: a
      clinical study.
AB  - CONTEXT: Electric pulp testers (EPTs) are widely used as diagnostic aid in
      dentistry for dental pulp. This delivers enough current to overcome enamel and
      dentin resistance and to stimulate the myelinated sensory fibers at the junction
      of pulp and dentin. Such testing requires the electrode to be in contact with the
      surface of the tooth, with optimal positions identified for anterior teeth,
      premolars, and molars. AIMS: To determine the best site position of EPT on
      premolars. The objective of electric pulp testing was to determine the
      sensibility of each premolar at the lowest sensory response threshold. SETTINGS
      AND DESIGN: Clinical study Materials and Methods: The premolars of 20 patients
      between 13 and 15 years accompanied with parents, free of restorations, and
      caries were selected. Five sites on the crown were tested with EPT for minimum of
      four times. STATISTICAL ANALYSIS USED: One-way analysis of variance test and the
      Tukey's honestly significant difference test. RESULTS: The lowest threshold
      response was noted at the incisal edge of the tooth; the middle third had a
      higher threshold among all the different placement of electrode. Statistically
      significant difference was observed for occlusal surface in terms of region of
      placement of electrode. CONCLUSIONS: This experiment found the best electrode
      site for pulp testing in premolars. The appropriate EPT site was on the occlusal
      surface of maxillary and mandibular premolars.

PMID- 25872635
TI  - Autologous reattachment of complicated crown fractures using intra canal
      anchorage: report of two cases.
AB  - Crown fractures are most common form of dental trauma sustained by children and
      adolescents. Major portion of these crown fractures are uncomplicated.
      Complicated crown fractures though infrequent and account only 4-16%, is an
      enigma to any clinician. Autologus reattachment of the tooth fragment is a simple
      and conservative procedure in managing such crown fractures. The present article
      intends to report the successful clinical management of Autologus tooth fragment
      reattachment in two complicated crown fractures. 

PMID- 25872634
TI  - An in vitro analysis of the cariogenic and erosive potential of pediatric liquid
      analgesics.
AB  - BACKGROUND: Analgesics such as Ibuprofen and Paracetamol, which are clinically
      used for the treatment of fever and/or pain, are among the most frequently used
      pediatric medicines. However, the properties of these preparations determine
      their cariogenic and erosive potential. AIMS: The main objective of this study
      was to analyze the pH, viscosity and total sugar content in a variety of Syrian
      pediatric liquid analgesics (PLA). SETTING AND DESIGN: A total of 16 available
      liquid analgesics that belong to the Paracetamol and Ibuprofen group were
      analysed. MATERIALS AND METHODS: The endogenous pH was measured using a digital
      pH meter, the viscosity was measured using a digital rotational viscometer and
      the total sugar content was performed according to Fehling method. STATISTICAL
      ANALYSIS: Data were presented by means of descriptive statistics (mean, standard
      deviation, minimum and maximum values). RESULTS: The mean endogenous pH of PLA
      was 4.63 +/- 0.57 ranging between 3.93 and 5.68, and almost all of analgesics
      (93.8%) had pH values <=5.5. The mean viscosity of PLA was 243.56 +/- 186.6 cP
      and varied between 20.5 cP and 640.5 cP. Sugars were detected in 11 (68.75%)
      analgesics, and varied considerably among sugar-containing analgesics from 5.38
      to 69.4 (g/100 mL) with a mean concentration of 24.97 +/- 23.24 g/100 mL.
      CONCLUSION: PLA are potentially cariogenic and erosive because of low pH, high
      viscosity and high total sugar content. This may increase our concerns about the
      dental health of children who take liquid analgesics frequently or when long-term
      treatment is indicated.

PMID- 25872636
TI  - Molar incisor hypomineralization: considerations about treatment in a controlled
      longitudinal case.
AB  - Molar incisor hypomineralization (MIH) is a defect in the tooth enamel of
      systemic origin and may affect one or all four first permanent molars frequently
      associated with the permanent incisors. This case reports a 7-year-old child with
      severe MIH in the permanent molars associated with tooth decay and intense pain.
      In the first stage of treatment, therapy was performed with fluoride varnish and
      restoration with glass ionomer cement (GIC). After 6 years of clinical and
      radiographic follow-up, the restorations presented wear and fractures on the
      margins, indicating their replacement with composite resin. Severe cases of MIH
      in the early permanent molars can be treated with varnish and GIC to restore the
      patient's comfort and strengthen the hypomineralized dental structures. The
      clinical and radiographic monitoring frequently indicated when the restoration
      with composite resin should be performed. 

PMID- 25872637
TI  - Congenital infiltrating lipomatosis of face: case report and review of
      literature.
AB  - Hemifacial hyperplasia is a rare condition causing unilateral enlargement of all
      tissues. We report a case of progressive facial asymmetry caused by congenital
      infiltrating lipomatosis of the face in a 6-year-old boy. The approach to
      diagnosis in our case is discussed along with a review of cases reported in the
      literature. 

PMID- 25872638
TI  - Clinical efficacy of open reduction and semirigid internal fixation in management
      of displaced pediatric mandibular fractures: a series of 10 cases and surgical
      guidelines.
AB  - AIM: To evaluate the efficacy of open reduction and semirigid internal fixation
      in the management of displaced pediatric mandibular fractures. METHOD: Ten
      patients with displaced mandibular fractures treated with 1.5 mm four holed
      titanium mini-plate and 4 mm screws which were removed within four month after
      surgery. RESULTS: All cases showed satisfactory bone healing without any growth
      disturbance. CONCLUSION: Open reduction and rigid internal fixation (ORIF) with
      1.5 mm titanium mini- plates and 4 mm screws is a reliable and safe method in
      treatment of displaced paediatric mandibular fractures.

PMID- 25872639
TI  - Temporomandibular joint ankylosis in child: a case report.
AB  - BACKGROUND: Ankylosis of the temporomandibular joint (TMJ) is an intracapsular
      union of the disc-condyle complex to the temporal articular surface that
      restricts mandibular movements, including the fibrous adhesions or bony fusion
      between condyle, disc, glenoid fossa, and eminence. It is a serious and disabling
      condition that may cause problems in mastication, digestion, speech, appearance,
      and hygiene. CASE REPORT: This report describes a case of a 12-year-old girl with
      inability to open her mouth, diagnosed with unilateral right bony TMJ ankylosis.
      The surgical approach consisted of gap arthroplasty with interpositional
      temporalis muscle flap followed by vigorous physiotherapy. CONCLUSION: The
      treatment of TMJ ankylosis poses a significant challenge because of technical
      difficulties and a high incidence of recurrence. Its treatment includes the
      orthodontist, oral and maxillofacial surgeon, pediatric dentist, and psychologist
      and physical therapist as part of the healthcare team.

PMID- 25872640
TI  - Epigallocatechin-3-gallate and zinc provide anti-apoptotic protection against
      hypoxia/reoxygenation injury in H9c2 rat cardiac myoblast cells.
AB  - It has previously been demonstrated that phosphatidylinositol-3-kinase (PI3K)/Akt
      and cleaved caspase-3 serve critical roles in the apoptosis of cardiac myocytes
      following ischemia/reperfusion injury. Epigallocatechin-3-gallate (EGCG), the
      predominant catechin component of green tea, has been reported to have potential
      cardioprotective effects in primary cultures of cardiac myocytes exposed to I/R
      injury, mediated through inhibition of signal transducers and activators of
      transcription-1 activity. In addition, it is also known that the biological
      behavior of EGCG may be influenced by metal ions, for example the
      hepatoprotective activity of EGCG has been reported to be enhanced by zinc. In
      the present study, the protective effects of EGCG with zinc were assessed on
      cultures of rat cardiac myoblasts exposed to hypoxia/reoxygenation (H/R) injury.
      H9c2 cells were subjected to 3-h hypoxia, followed by 1-h reperfusion. EGCG
      and/or zinc were perfused prior to induced hypoxic stress. It was demonstrated
      that when EGCG interacted with zinc, the anti-apoptotic activity was
      significantly enhanced. To the best of our knowledge, the current study was the
      first to demonstrate that EGCG + Zn(2+) protects H9c2 cells against H/R injury
      through activation of the PI3K/Akt pathway, as determined by western blotting.
      Since EGCG + Zn(2+) may, at least in part, protect cardiac myocytes against H/R
      induced apoptotic cell death, the PI3K/Akt pathway of EGCG may be enhanced by its
      interactions with zinc during H/R injury. Furthermore, it was suggested that a
      similar procedure may be implemented in a clinical setting, in order to maximize
      PI3K/Akt activation levels in patients with acute coronary artery disease. EGCG
      and zinc may therefore represent effective agents for use in the prevention of
      I/R injury in clinical practice.

PMID- 25872641
TI  - Effect of a nutrition education programme on clinical status and dietary
      behaviours of adults with type 2 diabetes in a resource-limited setting in South
      Africa: a randomised controlled trial.
AB  - OBJECTIVE: To evaluate the effect of a participant-customised nutrition education
      programme on glycated Hb (HbA(1c)), blood lipids, blood pressure, BMI and dietary
      behaviours in patients with type 2 diabetes mellitus. DESIGN: A randomised
      controlled trial. The control group (n 41) received education materials. The
      intervention group (n 41) received the same education materials and participated
      in eight weekly (2-2.5 h) group nutrition education sessions and follow-up
      sessions. Outcomes were assessed at 6 and 12 months. An intention-to-treat
      analysis was conducted. ANCOVA compared the groups (adjustments for baseline
      values, age, sex and clinic). SETTING: Two community health centres, Moretele sub
      district (North West Province), South Africa. SUBJECTS: Adults (aged 40-70 years)
      with type 2 diabetes, HbA(1c) >=8 %. RESULTS: Differences in HbA(1c) (primary
      outcome) were -0.64 % (P=0.15) at 6 months and -0.63 % (P=0.16) at 12 months in
      favour of the intervention group. Starchy-food intake was significantly lower in
      the intervention group, 9.3 v. 10.8 servings/d (P=0.005) at 6 months and 9.9 v.
      11.9 servings/d (P=0.017) at 12 months. Median energy intake was significantly
      lower in the intervention group at 12 months (5988 v. 6946 kJ/d, P=0.017). No
      significant group differences in BMI, lipid profile, blood pressure and intakes
      of macronutrients, vegetables and fruits were observed. CONCLUSIONS: Nutrition
      education was not efficacious on HbA(1c); however, it improved specific dietary
      behaviours. Group education and hands-on activities appeared to contribute to the
      improvement. Optimal goal setting and self-efficacy training/assessment could
      benefit future nutrition education programmes for people with type 2 diabetes
      mellitus in resource-limited settings.

PMID- 25872642
TI  - Arabidopsis FHY3/CPD45 regulates far-red light signaling and chloroplast division
      in parallel.
AB  - CPD45 (chloroplast division45),which is also known as FHY3 (far-red elongated
      hypocotyl3), is a key factor in the far-red light signaling pathway in
      Arabidopsis. We previously showed that FHY3/CPD45 also regulates chloroplast
      division. Because light is also a regulator of chloroplast development and
      division, we sought to clarify the relationship between far-red light signaling
      and chloroplast division pathways. We found that the chloroplast division mutant
      arc5-3 had no defect in far-red light sensing, and that constitutive
      overexpression of ARC5 rescued the chloroplast division defect, but not the
      defect in far-red light signaling, of cpd45. fhy1, which is defective in far-red
      light signaling, exhibited normal chloroplast division. Constitutive
      overexpression of FHY1 rescued the far-red light signaling defect, but not the
      chloroplast division defect, of cpd45. Moreover, ARC5 and FHY1 expression were
      not affected in fhy1 and arc5-3, respectively. Based on these results, we propose
      that FHY3/CPD45 regulates far-red light signaling and chloroplast division in
      parallel by activating the expression of FHY1 and ARC5 independently. This work
      demonstrates how relationships between different pathways in a gene regulatory
      network can be explored. 

PMID- 25872643
TI  - High-throughput and quantitative assessment of enhancer activity in mammals by
      CapStarr-seq.
AB  - Cell-type specific regulation of gene expression requires the activation of
      promoters by distal genomic elements defined as enhancers. The identification and
      the characterization of enhancers are challenging in mammals due to their genome
      complexity. Here we develop CapStarr-Seq, a novel high-throughput strategy to
      quantitatively assess enhancer activity in mammals. This approach couples capture
      of regions of interest to previously developed Starr-seq technique. Extensive
      assessment of CapStarr-seq demonstrates accurate quantification of enhancer
      activity. Furthermore, we find that enhancer strength is associated with binding
      complexity of tissue-specific transcription factors and super-enhancers, while
      additive enhancer activity isolates key genes involved in cell identity and
      function. The CapStarr-Seq thus provides a fast and cost-effective approach to
      assess the activity of potential enhancers for a given cell type and will be
      helpful in decrypting transcription regulation mechanisms. 

PMID- 25872644
TI  - Is there a role for ADORA2A polymorphisms in levodopa-induced dyskinesia in
      Parkinson's disease patients?
AB  - AIM: Levodopa is first line treatment of Parkinson's disease (PD). However, its
      use is associated with the presence of motor fluctuations and dyskinesias. In
      recent years, adenosine A2A receptor (A2AR) is rising as a therapeutic target for
      PD. The aim of the present study was to investigate whether ADORA2A is associated
      with levodopa adverse effects. PATIENTS & METHODS: Two hundred and eight PD
      patients on levodopa therapy were investigated. rs2298383 and rs3761422 at the
      ADORA2A gene were genotyped by allelic discrimination assays. RESULTS: A trend
      for association was observed for both polymorphism and diplotypes with
      dyskinesia. CONCLUSION: The present results should be considered as positive
      preliminary evidence. Further studies are needed to determine the association
      between ADORA2A and dyskinesia. Original submitted 3 December 2014; Revision
      submitted 13 February 2015.

PMID- 25872645
TI  - Hedgehog signaling is involved in the BMP9-induced osteogenic differentiation of
      mesenchymal stem cells.
AB  - Nonunion is a serious complication of a bone fracture that may occur in any bone
      of the skeletal system. It occurs when a broken bone fails to heal. Mesenchymal
      stem cell (MSC)-based tissue engineering technology has been considered an
      efficient method to improve the healing rate of nonunions. Although previous
      studies have demonstrated that bone morphogenetic protein 9 (BMP9) is highly
      capable of promoting the osteogenic differentiation of MSCs, the mechanisms
      involved remain largely unclear. In the present study, we investigated the
      possible involvement and the detailed role of Hedgehog (Hh) signaling in the BMP9
      induced osteogenic differentiation of MSCs. It was found that BMP9 exerts an
      effect on Hh signaling in MSCs. The expression levels of early markers of BMP9
      induced osteogenic differentiation, such as alkaline phosphatase (ALP) activity,
      and late markers of osteogenic differentiation, such as matrix mineralization, as
      well as the expression levels of osteopontin (OPN) and osteocalcin (OCN) were
      decreased by the Hh signaling inhibitor, cyclopamine, whereas these levels were
      increased by the Hh signaling agonist, purmorphamine. Furthermore, the BMP9
      induced transcriptional activity of Smad1/5/8 and the expression of pivotal
      osteogenic transcription factors were reduced by cyclopamine, and were increased
      by purmorphamine. Taken together, our results demonstrate that BMP9 exerts an
      effect on Hh signaling in MSCs. What is most noteworthy, however, is that the
      inhibition or enhancement of Hh signaling resulted in the reduction and
      augmentation of the BMP9-induced osteogenic differentiation of MSCs,
      respectively, suggesting that Hh signaling is involved and plays a regulatory
      role in the osteogenic differentiation of MSCs induced by BMP9.

PMID- 25872646
TI  - Whole-exome sequencing implicates UBE3D in age-related macular degeneration in
      East Asian populations.
AB  - Age-related macular degeneration (AMD) is a leading cause of irreversible central
      blindness among the elderly worldwide. We use exome sequencing to analyse
      nonsynonymous single-nucleotide variants (SNVs) across the whole genome of 216
      neovascular AMD cases and 1,553 controls. As a follow-up validation, we evaluate
      3,772 neovascular AMD cases and 6,942 controls from five independent cohorts in
      the East Asian population. Here we show strong evidence of an association at a
      novel, missense SNV, rs7739323, which is located in the ubiquitin protein ligase
      E3D (UBE3D) gene (Pmeta=1.46 * 10(-9), odds ratio (OR)=0.74, 95% confidence
      interval (CI): 0.63-0.88). Furthermore, ablation of the UBE3D protein lead to an
      abnormal amount of pigment granules deposited in retinal pigment epithelium
      microvilli area and an abnormal response on electroretinography (ERG) in UBE3D(+/
      ) heterozygous mice. Our findings indicate that the ubiquitin-proteasome system
      may play a role in the pathogenesis of neovascular AMD. 

PMID- 25872647
TI  - Recombinant Salmonella-based CEACAM6 and 4-1BBL vaccine enhances T-cell immunity
      and inhibits the development of colorectal cancer in rats: In vivo effects of
      vaccine containing 4-1BBL and CEACAM6.
AB  - The present study aimed to determine the effect of recombinant Salmonella
      (SL3261)-based CEACAM6 and 4-1BB ligand (4-1BBL) vaccine on the development of
      colorectal cancer in rats and the potential immune mechanisms involved.
      Attenuated Salmonella typhimurium (vaccine strain)-carrying plasmids pIRES
      CEACAM6, pIRES-4-1BBL and pIRES-CEACAM6-4-1BBL were constructed. The rats were
      administered subcutaneous injections of 1,2-dimethyl-hydrazine (DMH) once a week
      for 18 weeks. Eight weeks after the first injection, the rats were divided into
      the pIRES/SL3261, pIRES-4-1BBL/SL3261, pIRES-CEACAM6/SL3261 and pIRES-CEACAM6-4
      1BBL/SL3261 groups, and fed with corresponding vaccine strains. The rats were
      then sacrificed, the number of colon tumors were recorded, and the Dukes' stage
      were evaluated. CD3, CD4, CD8, CD56, FOXP3 and CEACAM6 expression in tumor
      tissues was determined by immunohistochemical staining. Compared with the
      expression levels in the pIRES/SL3261 group, similar levels of CD3+, CD8+ and
      CD56+ expression were identified for the pIRES-CEACAM6/SL3261 group of rats.
      Additionally, a comparable number of tumors was detected in the pIRES-4
      1BBL/SL3261 and pIRES-CEACAM6/SL3261 groups. By contrast, a significantly fewer
      number of tumors, albeit with a higher density of CD3+CD8+, CD56+ and a lower
      density of Foxp3+ tumor-infiltrating lymphocyte (TIL) cells was detected in the
      pIRES-CEACAM6-4-1BBL/SL3261 group of rats. The results indicated that vaccination
      with recombinant attenuated Salmonella harboring the CEACAM6 and 4-1BBL gene
      efficiently increased the number of CD3+CD8+ TIL and NK cells, decreased the
      number of FOXP3 cells and inhibited the development of DMH-induced colorectal
      cancer in rats. 

PMID- 25872648
TI  - The relationship between metabolic syndrome, its components, and erectile
      dysfunction: a systematic review and a meta-analysis of observational studies.
AB  - INTRODUCTION: The studies examining the association between metabolic syndrome
      (MetS), its components, and erectile dysfunction (ED) should be reevaluated to
      arrive at comprehensive results in this field. AIM: Our aim was to gather
      individual studies in order to achieve a more reliable conclusion regarding the
      relationship between MetS, its components, and ED. METHODS: Three investigators
      searched the Pubmed-Medline and Embase databases using the key words "metabolic
      syndrome" and "erectile dysfunction." The individual studies were evaluated for
      selection of suitable studies. MAIN OUTCOME MEASURES: Eight studies that met all
      inclusion criteria were chosen, and a pooled analysis of odds ratio (ORs) between
      MetS and ED was calculated. The components of MetS to ED were also estimated.
      RESULTS: Eight observational studies with a total of 12,067 participants were
      examined. The overall analysis revealed a 2.6-fold increase in patients with MetS
      having ED (2.67[1.79-3.96]; P < 0.0001). All individual components of MetS except
      high-density lipoprotein level were also found to correlate with an increased
      prevalence of ED. Of those, fasting blood sugar was detected highest rate for ED
      with OR of 2.07 ([1.49-2.87]; P < 0.0001). CONCLUSIONS: Metabolic syndrome is
      associated with a high risk rate of ED, and patients with MetS should be informed
      about this association and encouraged to make lifestyle modifications to improve
      their general health and to limit cardiovascular risk as well as ED prevalence.
      However, manuscripts included in meta-analysis were observational studies that
      prohibits ascertainment of temporal associations and necessitates further
      prospective studies.

PMID- 25872650
TI  - Pro-Opiomelanocortin (POMC) Neurones, POMC-Derived Peptides, Melanocortin
      Receptors and Obesity: How Understanding of this System has Changed Over the Last
      Decade.
AB  - Following the cloning of the melanocortin receptor and agouti protein genes, a
      model was developed for the central melanocortin system with respect to the
      regulation of energy and glucose homeostasis. This model comprised leptin
      regulation of melanocortin peptides and agouti-related peptide (AgRP) produced
      from central pro-opiomelanocortin (POMC) and AgRP neurones, respectively, as well
      as AgRP competitive antagonism of melanocortin peptides activating melanocortin 4
      receptor (MC4R) to Galphas and the cAMP signalling pathway. In the last decade,
      there have been paradigm shifts in our understanding of the central melanocortin
      system as a result of the application of advanced new technologies, including Cre
      LoxP transgenic mouse technology, pharmacogenetics and optogenetics. During this
      period, our understanding of G protein coupled receptor signal transduction has
      also dramatically changed, such that these receptors are now known to exist in
      the plasma membrane oscillating between various inactive and active
      conformational states, and the active states signal through G protein-dependent
      and G protein-independent pathways. The present review focuses on evidence
      obtained over the past decade that has changed our understanding of POMC gene
      expression and regulation in the central nervous system, POMC and AgRP neuronal
      circuitry, neuroanatomical functions of melanocortin receptors, melanocortin 3
      receptor (MC3R) and MC4R, and signal transduction through MC3R and MC4R. 

PMID- 25872649
TI  - Pain reduction with oral methotrexate in knee osteoarthritis, a pragmatic phase
      iii trial of treatment effectiveness (PROMOTE): study protocol for a randomized
      controlled trial.
AB  - BACKGROUND: Osteoarthritis (OA) is the fastest growing cause of disability
      worldwide. Current treatments for OA are severely limited and a large proportion
      of people with OA live in constant, debilitating pain. There is therefore an
      urgent need for novel treatments to reduce pain. Synovitis is highly prevalent in
      OA and is associated with pain. In inflammatory arthritides such as rheumatoid
      arthritis, methotrexate (MTX) is the gold standard treatment for synovitis and
      has a well-known, acceptable toxicity profile. We propose that using MTX to treat
      patients with symptomatic knee OA will be a practical and safe treatment to
      reduce synovitis and, consequently, pain. METHODS/DESIGN: Pain Reduction with
      Oral Methotrexate in knee Osteoarthritis, a pragmatic phase III trial of
      Treatment Effectiveness (PROMOTE) is an investigator-initiated, multi-centre,
      randomized, double-blind, pragmatic placebo-controlled trial. A total of 160
      participants with symptomatic knee OA will be recruited across primary and
      secondary care sites in the United Kingdom and randomized on a 1:1 basis to
      active treatment or placebo, in addition to usual care, for 12 months. As is
      usual practice for MTX, dosing will be escalated over six weeks to 25 mg (or
      maximum tolerated dose) weekly for the remainder of the study. The primary
      endpoint is change in average knee pain during the past week (measured on an 11
      point numerical rating scale) between baseline and six months. Secondary
      endpoints include other self-reported pain, function and quality-of-life
      measures. A health economics analysis will also be performed. A magnetic
      resonance imaging substudy will be conducted to provide an explanatory mechanism
      for associated symptom change by examining whether MTX reduces synovitis and
      whether this is related to symptom change. Linear and logistic regression will be
      used to compare changes between groups using univariable and multivariable
      modelling analyses. All analyses will be conducted on an intention-to-treat
      basis. DISCUSSION: The PROMOTE trial is designed to examine whether MTX is an
      effective analgesic treatment for OA. The MRI substudy will address the
      relationship between synovitis and symptom change. This will potentially provide
      a much needed new treatment for knee OA. TRIAL REGISTRATION: Current Controlled
      Trials identifier: ISRCTN77854383 (registered: 25 October 2013).

PMID- 25872651
TI  - Effects of study design and allocation on self-reported alcohol consumption:
      randomized trial.
AB  - BACKGROUND: What participants think about the nature of a study might affect
      their behaviour and bias findings. We tested two hypotheses: (1) participants
      told they were in an intervention trial would report lower alcohol consumption at
      follow-up than those told they were in a cohort study; (2) participants told they
      were in the intervention group in a trial would have lower alcohol consumption at
      follow-up than those told they were in the control group. METHODS: Students from
      four universities (N = 72,903) were invited to participate in a 'research project
      on student drinking'. Of 10,415 respondents, 6,788 were moderate to heavy
      drinkers and were randomized. Group A ('cohort') were informed their drinking
      would be assessed at baseline and again in one month. Group B ('control') were
      told the study was an intervention trial and they were in the control group.
      Group C ('intervention') were told the study was an intervention trial and they
      were to receive the intervention. All were assessed and directed to read
      identical online alcohol education material. Whether and how long they accessed
      the material were recorded. One month later, alcohol intake was reassessed.
      RESULTS: In relation to hypothesis 1, there were no differences between the
      groups on the prespecified outcome measures. In relation to hypothesis 2, there
      were no differences though all point estimates were in the hypothesized direction
      (that is, 'intervention' < 'control'). The 'cohort' and 'control' groups accessed
      the material to a similar extent (59% versus 57%) while the 'intervention' group
      were more likely to access it (78%) and to read it for longer (median 35 s (25th
      and 75th percentiles: 6, 97) versus medians of 7 s (0, 28) and 8 s (4, 42) for
      the 'cohort' and 'control' groups, respectively). CONCLUSIONS: Although the
      context given to the research participants significantly influenced access to the
      online information and reading time, this did not translate into any effect on
      drinking behaviour, for either hypothesis. This might be because of failure in
      the experimental paradigm or the possibility of weaker effects using the online
      approach. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry
      ACTRN12610000846022.

PMID- 25872652
TI  - Electrochemical Interrogation of Kinetically-Controlled Dendritic DNA/PNA
      Assembly for Immobilization-Free and Enzyme-Free Nucleic Acids Sensing.
AB  - We present an immobilization-free and enzyme-free electrochemical nucleic acid
      sensing strategy, which uses kinetically controlled dendritic assembly of DNA and
      peptide nucleic acid (PNA). In the presence of a target sequence, ferrocene
      labeled PNA probes (Fc-PNAs) and specially designed DNA strands are autonomously
      assembled into dendritic nanostructures through a cascade of toehold-mediated
      strand displacement reactions. The consumption of freely diffusible Fc-PNAs
      (neutrally charged), due to incorporation to DNA/PNA dendrimer, results in a
      significant electrochemical signal reduction of Fc on a negatively charged
      electrode from which the hyperbranched and negatively charged dendrimer of
      DNA/PNA would be electrostatically repelled. The cascade-like assembly process
      and large electrostatic affinity difference between Fc-PNAs and DNA/PNA dendrimer
      toward the sensing electrode offer a detection limit down to 100 fM and an
      inherently high specificity for detecting single nucleotide polymorphisms. The
      target-triggered mechanism was examined by PAGE analysis, and morphologies of the
      assembled dendrimers were verified by AFM imaging. 

PMID- 25872654
TI  - Novel ultra-incompressible phases of Ru2C.
AB  - The crystal structures of Ru2C were extensively investigated using the structure
      searching method coupled with first-principles calculations. In contrast to the
      previously proposed P-3m1 phase, two energetically more favorable structures with
      space groups P-31m and P63/mmc were found, which are stable at pressure ranges of
      0-32 GPa and 32-50 GPa, respectively. The dynamical stabilities of both phases at
      ambient and high pressures are confirmed by the phonon dispersions. Further
      calculations indicate that the two new predicted phases are ultra-incompressible
      metals due to a strong covalent Ru-C bond. 

PMID- 25872653
TI  - Trauma-focused cognitive behaviour therapy versus treatment as usual for post
      traumatic stress disorder (PTSD) in young children aged 3 to 8 years: study
      protocol for a randomised controlled trial.
AB  - BACKGROUND: Following horrific or life-threatening events approximately 10 to 15%
      of young children develop post traumatic stress disorder (PTSD). The symptoms of
      this disorder are distressing - nightmares, flashbacks, anger outbursts and
      disturbed play. These symptoms cause major disruption to a child's functioning
      and, if left untreated, can persist for many years. As yet, there are no
      established empirically-validated treatments for PTSD in young children. Trauma
      focused cognitive behaviour therapy (TF-CBT) is a psychological intervention that
      is effective in treating the disorder in older children (8 to 12 years),
      adolescents and adults. This study examines TF-CBT adapted for children aged
      between 3 and 8 years. METHODS/DESIGN: This protocol describes a two-arm
      exploratory randomised controlled trial comparing TF-CBT to treatment as usual
      (TAU) in children aged 3 to 8 years with a principal diagnosis of PTSD following
      a single-event discrete trauma. Using a half-crossover design, 44 participants
      will be randomly allocated to receive the intervention or to receive TAU. Those
      allocated to TAU will be offered TF-CBT at the end of the 'treatment' period
      (approximately 12 weeks) if still indicated. The primary outcome is PTSD
      diagnosis according to DSM-5 criteria for children 6 years and younger at post
      treatment. Secondary outcomes include effects on co-morbid diagnoses and changes
      in emotion and trauma symptoms at each of the follow-up points (post-treatment, 3
      months, 12-months). Additionally, broader efficacy will be considered with regard
      to treatment feasibility, acceptability and service utilisation. The key targets
      of the intervention are trauma memory, the interpretation of the meaning of the
      event, and the management of symptoms. DISCUSSION: This is the first European
      trial to examine the efficacy of TF-CBT in alleviating PTSD in very young
      children. As well as providing much-needed data on the utility of the
      intervention, this exploratory trial will also allow us to gather important
      information about the feasibility of delivering the treatment in UK National
      Health Service (NHS) settings, and its acceptability to the children and their
      families. This study will highlight aspects of the intervention that need
      improvement or modification in preparation for a full-scale evaluation in a
      larger sample. TRIAL REGISTRATION: ISRCTN35018680 , registered on 18 November
      2013.

PMID- 25872655
TI  - Melia azedarach extract stimulates melanogenesis through increase of tyrosinase
      related protein 1 expression in B16F10 mouse melanoma cells.
AB  - Melia azedarach (MA) has been used in folk medicine in Asia for the treatment of
      several diseases. Several constituents from MA possess anti-herpetic, anti
      angiogenic and anticancer properties. The aim of the present study was to
      investigate the effect of a 70% ethanol extract of MA on melanogenesis and the
      underlying mechanisms involved. A B16F10 mouse melanoma cell line was used in our
      experiments. Treatment of B16F10 cells with the MA extract (10, 20 and 40 ug/ml)
      increased melanin content in a concentration-dependent manner without
      cytotoxicity at 24 h. Further experiments indicated that the MA extract (20
      ug/ml) increased melanin content as early as at 4 h after treatment.
      Additionally, although the MA extract did not affect intracellular tyrosinase
      activity and the protein levels of tyrosinase and tyrosinase-related protein-2
      (TRP-2) at 2 and 4 h after treatment, the MA extract increased TRP-1 protein
      expression at both time points. However, no significant effect of the MA extract
      treatment on TRP-1 mRNA level at the time points measured was observed. In
      conclusion, the results from the present study demonstrate that the MA extract
      increases melanogenesis through the upregulation of TRP-1 protein expression by
      post-transcriptional control in B16F10 cells and suggest that the MA extract can
      be viewed as a rapid inducer of melanogenesis, thus rendering it a potential
      treatment for hypopigmentation diseases including vitiligo.

PMID- 25872656
TI  - Effect of pretreatments and air-frying, a novel technology, on acrylamide
      generation in fried potatoes.
AB  - This paper investigated the effect of air-frying technology, in combination with
      a pretreatment based of soaking the samples in different chemical agent solutions
      (citric acid, glycine, calcium lactate, sodium chloride, or nicotinic acid
      [vitamin B3]), on the generation of acrylamide in fried potatoes. The influence
      of reducing sugars on the development of surface's color was also analyzed. The
      experiments were conducted at 180  degrees C by means of air-frying and deep-oil
      frying, as a reference technology. Based on the evolution of color crust with
      frying time, it could be concluded that the rate of Maillard reaction decreased
      as the initial reducing sugars content increased in the raw material, and was
      also lower for deep-oil-frying than for air-frying regardless of pretreatments
      applied. Air-frying reduced acrylamide content by about 90% compared with
      conventional deep-oil-frying without being necessary the application of a
      pretreatment. However, deep-oil fried potatoes pretreated with solutions of
      nicotinic acid, citric acid, glycine at 1%, and NaCl at 2% presented much lower
      acrylamide levels (up to 80% to 90% reduction) than nonpretreated samples.

PMID- 25872657
TI  - B7-H3 silencing inhibits tumor progression of mantle cell lymphoma and enhances
      chemosensitivity.
AB  - B7-H3 (CD276), known as a member of B7 immunoregulatory family, is a type I
      transmembrane glycoprotein aberrantly expressed in numerous types of cancer and
      associated with poor prognosis. However, the role of B7-H3 in oncogenesis and
      chemosensitivity of mantle cell lymphoma (MCL) remains unknown. We determined the
      effects of downregulating B7-H3 expression on tumor progression and the
      sensitivity of chemotherapeutic drug in mantle cell lymphoma. B7-H3 knockdown was
      performed using lentivirus transduction in the Maver and Z138 mantle cell
      lymphoma cell lines, respectively. The effects of B7-H3 on cell proliferation,
      cycle, migration and invasion were investigated by CCK-8 assay, methyl cellulose
      colony forming assay, PI staining, and Transwell assays in vitro. By establishing
      Maver and Z138 xenograft models, the effects of B7-H3 on tumorigenicity were
      observed, and Ki-67 and PCNA was detected by immunohistochemistry. The
      downregulation of B7-H3 significantly decreased tumor proliferation in MCL in
      vitro and in vivo. In the B7-H3 knockdown groups of Maver and Z138 xenograft
      models, the mean inhibition rate of tumor growth was 59.1 and 65.0% (p=0.010 and
      0.003), and the expression of both Ki-67 and PCNA were significantly lower,
      respectively. After B7-H3 silencing, the cell cycles of Maver and Z138 were both
      arrested at G0/G1 phase, and the cell migration rates and invasion capacity were
      decreased as well. Moreover, the impacts of B7-H3 RNAi on the antitumor effect of
      chemotherapy drugs were determined with CCK-8 and Annexin V-FITC/PI assays in
      vitro and with xenograft models in vivo. The silencing of B7-H3 increased the
      sensitivity of Maver and Z138 cells to rituximab and bendamustine and enhanced
      the drug-induced apoptosis, respectively. Our study demonstrates for the first
      time that B7-H3 promotes mantle cell lymphoma progression and B7-H3 knockdown
      significantly enhances the chemosensitivity. This may provide a new therapeutic
      approach to mantle cell lymphoma.

PMID- 25872658
TI  - Monitoring the Dissolution Mechanisms of Amorphous Bicalutamide Solid Dispersions
      via Real-Time Raman Mapping.
AB  - Real-time in situ Raman mapping has been employed to monitor, during dissolution,
      the crystallization transitions of amorphous bicalutamide formulated as a
      molecular dispersion in a copovidone VA64 matrix. The dissolution performance was
      also investigated using the rotating disc dissolution rate methodology, which
      allows simultaneous determination of the dissolution rate of both active
      ingredient and polymer. The dissolution behavior of two bicalutamide:copovidone
      VA64 dispersion formulations, containing 5% (w/w) and 50% (w/w) bicalutamide,
      respectively, was investigated, with the aim of exploring the effect of
      increasing the bicalutamide loading on the dissolution performance. Spatially
      time-resolved Raman maps generated using multivariate curve resolution indicated
      the simultaneous transformation of amorphous bicalutamide present in the 50% drug
      loaded extrudate into metastable polymorphic form II and low-energy polymorphic
      form I. Fitting a kinetic model and spatially correlating the data extracted from
      the Raman maps also allowed us to understand the re-crystallization mechanisms by
      which the low-energy form I appears. Form I was shown to crystallize mainly
      directly from the amorphous solid dispersion, with crystallization from the
      metastable form II being a minor contribution. 

PMID- 25872659
TI  - Complementary and alternative medicine use among paediatric emergency department
      patients.
AB  - AIM: To determine the period prevalence and nature of complementary and
      alternative medicine (CAM) use among paediatric emergency department (ED)
      patients and the perceptions of CAM among the CAM administrators. METHODS: A
      survey was undertaken in four Victorian EDs (January to September 2013). A
      convenience sample of parents/carers accompanying paediatric patients completed a
      self-administered questionnaire. The main outcome measures were CAM use and
      perceptions of CAM. RESULTS: The parents/carers of 883 patients participated.
      Three hundred eighty-eight (43.9%, 95% confidence interval (CI) 40.6-47.3) and 53
      (6.0%, 95% CI 4.6-7.8) patients had taken a CAM within the previous 12 months and
      on the day of presentation, respectively. There were no gender differences
      between CAM users and non-users (P = 0.83). The use of CAM was significantly more
      common among older patients (P < 0.001), those with European ethnicity (P =
      0.046) and among those with chronic disease (P < 0.01). Fish oil, garlic,
      chamomile and acidophilus were the most commonly used CAM. Only 4.4% of CAM use
      was reported to the ED doctor. There were reports of potentially dangerous CAM
      use (St John's wort, ginseng). Parents/carers who had administered CAM were more
      likely to report that CAMs are safe, drug free and could prevent illness (P <
      0.01). In addition, a number of this group reported that CAMs are more effective
      than prescription medicines and safe when taken with prescription medicines.
      CONCLUSION: CAM use is common among paediatric ED patients although rarely
      reported to the ED doctor. Parents/carers who administer CAM have differing
      perceptions of CAM safety from those who do not.

PMID- 25872661
TI  - Elevated serum creatinine in a patient with normal renal function: the value of
      Cystatin C.

PMID- 25872660
TI  - Insights into the Proton Transfer Mechanism of a Bilin Reductase PcyA Following
      Neutron Crystallography.
AB  - Phycocyanobilin, a light-harvesting and photoreceptor pigment in higher plants,
      algae, and cyanobacteria, is synthesized from biliverdin IXalpha (BV) by
      phycocyanobilin:ferredoxin oxidoreductase (PcyA) via two steps of two-proton
      coupled two-electron reduction. We determined the neutron structure of PcyA from
      cyanobacteria complexed with BV, revealing the exact location of the hydrogen
      atoms involved in catalysis. Notably, approximately half of the BV bound to PcyA
      was BVH(+), a state in which all four pyrrole nitrogen atoms were protonated. The
      protonation states of BV complemented the protonation of adjacent Asp105. The
      "axial" water molecule that interacts with the neutral pyrrole nitrogen of the A
      ring was identified. His88 Ndelta was protonated to form a hydrogen bond with the
      lactam O atom of the BV A-ring. His88 and His74 were linked by hydrogen bonds via
      H3O(+). These results imply that Asp105, His88, and the axial water molecule
      contribute to proton transfer during PcyA catalysis. 

PMID- 25872662
TI  - Chronic nephrotoxicity limits successful use of Tacrolimus in the management of
      adult steroid-dependent minimal change disease.

PMID- 25872663
TI  - Operating in an era of impact factor mania.

PMID- 25872664
TI  - Evaluating renal biopsy-associated hemorrhage complications by the equation and
      providing an early intervention: a single-center experience.
AB  - BACKGROUND: The aim was to evaluate the risk for major hemorrhage complications
      (MHC) prior to percutaneous renal biopsy and apply a specific procedure in high
      risk patients to decrease their incidence. Hemorrhage complications that required
      blood transfusion or other interventions were diagnosed as MHC. METHODS: One
      retrospective (Group A, n = 1314) and two prospective cohorts (Group B, n = 249
      and Group C, n = 422) were involved in the study. Group A was used to establish a
      risk equation for MHC, Group B to test its performance, and Group C to evaluate
      the efficacy of the proposed procedure to reduce MHC incidence. Group C was
      classified, based on the equation, into high-risk (C1) and low-risk (C2)
      patients, who received different interventions. The intervention in Group C1
      consisted of use of 18-gauge needles, a 12-h rest period post-operation, and
      reptilase injection; in Group C2, 16-gauge needles were used, with a 6-h rest,
      and no reptilase injection. Group B was also divided into B1 (high-risk) and B2
      (low-risk) using the same cut-off, for further comparison. RESULTS: (1) In Group
      A, 4.8% of patients experienced MHC and the equation: Logit (PMHC) = 0.022 * mean
      arterial pressure (mmHg) + 0.216 * bleeding time (min) - 0.011 * eGFR [ml/(min
      1.73 m(2))] - 0.894 * kidney length (cm) - 2.100 * renal cortical thickness (cm)
      + 6.225 (cutoff = -1.664) was established. (2) The area under the receiver
      operating characteristic curve was 0.848 (95 % CI 0.797-0.890) for Group B. (3)
      MHC occurred in 4.8 and 2.8% of patients in Group B and C, respectively; Group B1
      suffered significantly more frequent gross hematuria, hematoma and MHC than Group
      C1; however, no significant difference except for large hematoma was found
      between Groups B2 and C2 for all complications. CONCLUSIONS: The equation is
      reliable to predict the risk for MHC; the interventions proposed can decrease the
      incidence of MHC in high-risk patients.

PMID- 25872665
TI  - Clinical effectiveness and micro-perfusion alteration of Jingui external lotion
      in patients with knee osteoarthritis: study protocol for a randomized controlled
      trial.
AB  - BACKGROUND: Knee osteoarthritis is a major cause of disability in the aging
      population. Based on pathological, magnetic resonance imaging (MRI) and
      arthroscopy studies, progressive osteoarthritis involves all tissues of the joint
      and includes bone marrow lesions, synovial proliferation, fat pad inflammation,
      and high subchondral bone turnover. Recent research suggests that abnormal
      perfusion in bone marrow lesions, fat pads, and subchondral bone is associated
      with pain in knee osteoarthritis, and that dynamic contrast-enhanced MRI is a
      promising method for studying micro-perfusion alteration in knee osteoarthritis.
      Traditional Chinese Medicine approaches have been employed for thousands of years
      to relieve knee osteoarthritis pain. Among herbal medicines, the Jingui external
      lotion is the preferred and most commonly used method in China to reduce pain in
      patients with knee osteoarthritis; however, there is a lack of validated evidence
      for its effectiveness. The purpose of this study is to explore the effectiveness
      of Jingui external lotion for the management of painful knee osteoarthritis in a
      short-term study. In addition, we will assess micro-perfusion alteration in the
      patellar fat pad as well as the femur and tibia subchondral bone via dynamic
      contrast-enhanced MRI. METHODS/DESIGN: This trial is a randomized, controlled
      study. A total of 168 patients will be randomized into the following two groups:
      1) the Jingui external lotion group (treatment group); and 2) the placebo lotion
      group (control group). In both groups, lotion fumigation and external washing of
      the patients' knees will be administered twice a day for 14 consecutive days.
      Follow-up will be at regular intervals during a 4-week period with a visual
      analog scale to assess pain, and additional characterization with the Western
      Ontario and McMaster Universities Index score; rescue medication will be recorded
      as the extent and time pattern. In addition, micro-perfusion alteration in the
      patellar fat pad, femur and tibia subchondral bone will be assessed via dynamic
      contrast-enhanced MRI. DISCUSSION: This study will provide clinical evidence of
      the efficacy of Jingui external lotion in treating knee osteoarthritis, and it
      will be the first randomized controlled trial to investigate micro-perfusion
      alteration of knee osteoarthritis with Traditional Chinese Medicine external
      lotion via dynamic contrast-enhanced MRI. TRIAL REGISTRATION: ClinicalTrials.gov
      identifier: ChiCTR-TRC-14004727 ; 31 May 2014.

PMID- 25872666
TI  - Pit excision with phenolisation of the sinus tract versus radical excision in
      sacrococcygeal pilonidal sinus disease: study protocol for a single centre
      randomized controlled trial.
AB  - BACKGROUND: Excision of the pit of the sinus with phenolisation of the sinus
      tract and surgical excision are two treatment modalities for patients with
      sacrococcygeal pilonidal sinus disease. Phenolisation seems to have advantages
      over local sinus excision as it is performed under local anaesthesia with a
      relatively small surgical procedure, less postoperative pain, minor risk of
      surgical site infection (8.7%), and only a few days being unable to perform
      normal activity (mean of 2.3 days). The disadvantage may be the higher risk of
      recurrence (13%) and the necessity to perform a second phenolisation in a
      subgroup of patients. Wide surgical excision of sacrococcygeal pilonidal sinus
      disease has a recurrence rate of 4 to 11%. The disadvantages, however, are
      postoperative pain, high risk of surgical site infection, and a longer period
      being unable to perform normal activity (mean of 10 days). The objective of this
      study is to show that excision of the pit of the sinus of sacrococcygeal
      pilonidal sinus disease with phenolisation of the sinus tract is a successful
      first-time treatment modality for sacrococcygeal pilonidal sinus disease
      accompanied by a quicker return to normal daily activity compared to local
      excision of the sinus. METHODS/DESIGN: Patients with sacrococcygeal pilonidal
      sinus disease will be randomly allocated to excision of the pit of the sinus
      followed by phenol applications of the sinus tract or radical surgical excision
      of the sinus. Patients are recruited from a single Dutch teaching, non-university
      hospital. The primary endpoint is loss of days of normal activity/working days.
      Secondary endpoints are anatomic recurrence rate, symptomatic recurrence rate,
      quality of life, surgical site infection, time to wound closure, symptoms related
      to treatment, pain, usage of pain medication and total treatment time. To
      demonstrate a reduction of return to normal activity from 7.5 days in the
      excision group to 4 days in the phenolisation group, with 80% power at 5% alpha,
      a total sample size of 100 is required. DISCUSSION: This study is a randomised
      controlled trial to provide evidence that phenolisation of the sinus tract
      compared to radical excision reduces the total number of days unable to perform
      normal activity. TRIAL REGISTRATION: Dutch trial register NTR4043 , registered on
      24 June 2013.

PMID- 25872667
TI  - Evaluation of the immediate effect of acupuncture on pain, cervical range of
      motion and electromyographic activity of the upper trapezius muscle in patients
      with nonspecific neck pain: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Nonspecific neck pain can cause considerable suffering, possible
      disability and reductions in quality of life and productivity. The aim of the
      proposed study is to evaluate the immediate effect of acupuncture on pain,
      cervical range of motion and electromyographic activity of the upper trapezius
      muscle in patients with nonspecific neck pain. METHODS/DESIGN: A total of 12
      patients with nonspecific neck pain and 12 healthy subjects will be enrolled in a
      randomized, single-blind crossover study. Each subject will receive two forms of
      treatment in random order: a single session of traditional acupuncture
      (acupoints: triple energizer 5, 'Wai-guan' and large intestine 11, 'Qu-chi') and
      sham acupuncture. To eliminate carry-over treatment effects, a one-week wash-out
      period will be respected between sessions. Surface electromyography will be used
      to determine motor control in the upper trapezius muscle before and after
      treatment. The outcome measures in the group with neck pain will be a numerical
      pain rating scale (range: 0 (no pain) to 10 (maximum pain)), documentation of the
      pain area on a body chart and cervical range of motion. Comparisons before and
      after acupuncture treatment will demonstrate whether acupoints affect the
      activity of the upper trapezius muscle, pain and cervical range of motion.
      DISCUSSION: The purpose of this randomized clinical trial is to evaluate the
      immediate effect of acupuncture on pain, cervical range of motion and
      electromyographic activity of the upper trapezius muscle in patients with
      nonspecific neck pain. Data will be published after the study is completed. The
      study will support the practice of evidence-based physical therapy for
      individuals with nonspecific neck pain. TRIAL REGISTRATION: This trial was
      registered with Clinicaltrials.gov (identifier: NCT0984021 ) on 7 November 2013 (
      https://clinicaltrials.gov/ct2/show/NCT01984021 ).

PMID- 25872668
TI  - The cornea has "the nerve" to encourage immune rejection.

PMID- 25872669
TI  - [In Process Citation].

PMID- 25872670
TI  - [In Process Citation].

PMID- 25872671
TI  - [In Process Citation].

PMID- 25872672
TI  - [Atherectomy for peripheral arterial disease].
AB  - Symptomatic peripheral arterial disease is managed according to national and
      international guidelines and the number of vascular reconstructions performed
      each year has increased over the past decade mainly due to an increasing
      frequency of endovascular procedures. Atherectomy as an alternative to the
      established treatment of symptomatic peripheral arterial disease has recently
      been analysed in a Cochrane review. In Denmark, atherectomy is not performed and
      so far the evidence is poor as the method is not an alternative to the
      established treatment in this country. 

PMID- 25872673
TI  - [In Process Citation].

PMID- 25872674
TI  - [No evidence that diet has any influence on the aetiology of rheumatoid
      arthritis].
AB  - Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease affecting
      0,5-1% of the population. Several genetic and environmental factors are
      implicated in the aetiology of RA. The only well-established environmental risk
      factor is tobacco smoking. In this review we examine data linking intake of fatty
      acids, meat, antioxidants and vitamin D with the risk of RA. Although there is
      some tendency to show a protective effect of fatty acids from fish on RA,
      generally, evidence on dietary risk factors is scarce with a lack of statistical
      significance and reproducibility. 

PMID- 25872675
TI  - [Hypoglycaemia and hypocalcaemia in a gastric bypass-operated patient with high
      alcohol consumption and colectomia].
AB  - The combination of gastric bypass, colectomia, lack of substitution with minerals
      and vitamins, and alcohol consumption led to severe complications in a 57-year
      old man. He was submitted to different hospitals 25 times and seen in polyclinics
      39 times with no improvement in symptoms of postprandial neurohypoglycaemia,
      ortostatic hypotension and pronounced hypocalcaemia. The importance of frequent
      controls after gastric bypass in centres with specialists knowing the common
      complications after the operation and the need for nutritionel supplements is
      hereby emphasised. 

PMID- 25872676
TI  - [Chronic cough in children].
AB  - Cough in children is a common problem of various aetiologies. In the presence of
      specific findings diagnostics may be easy, but often the symptoms are few and
      unclear. Management involves specific diagnosing and it should be considered if
      the cough is acute, prolonged or chronic. The diagnosis depends on the quality of
      the cough evaluated as dry cough or wet, productive cough. Trials of treatment
      are often used to make a diagnosis, and any trial should be time-limited because
      natural resolution of cough is so common. Finally, giving thorough information to
      parents is crucial. 

PMID- 25872677
TI  - [Penile implants is a good last treatment option in erectile dysfunction].
AB  - When other treatments fail, penile implants represent the last treatment option
      in erectile dysfunction. The most commonly used implant is the inflatable three
      piece device, which allows the penis to be rigid for sexual intercourse and
      flaccid during the remaining time. Earlier penile implants were associated with
      high rates of infection and mechanical malfunction. However, technical
      improvements have greatly reduced these problems. This has resulted in a patient
      satisfaction rate of 80-90% in most studies. Thus, penile implants are a valid
      option in motivated patients with erectile dysfunction. 

PMID- 25872679
TI  - Microbiology review series: CF microbiology - -Towards 2020 and beyond.

PMID- 25872678
TI  - Clonal evolution of multidrug resistant hepatitis B virus during entecavir rescue
      therapy.
AB  - BACKGROUND & AIMS: Analysing the mutation pattern of multidrug resistance (MDR)
      is important in the treatment of chronic hepatitis B (CHB). In this study, the
      evolutionary pattern of MDR mutations was investigated in patients receiving
      entecavir (ETV) rescue therapy. METHODS: Eight CHB patients with lamivudine (LAM)
      and adefovir (ADV)-resistant mutations showing suboptimal response to ETV and to
      subsequent ETV-plus-ADV therapy were enrolled. The clonal evolution of the
      mutation pattern was investigated through direct sequencing, multiplex
      restriction fragment mass polymorphism (RFMP), and clonal analysis and the
      utility of these methods was compared. RESULTS: Among 160 clones at baseline,
      wild-type hepatitis B virus (HBV) was present in 62 (38.8%), LAM-resistant
      mutations in 92 (57.6%) and ADV-resistant mutations in 55 (34.4%). LAM-resistant
      mutations increased to 70.6% at the end of ETV therapy and increased to 74.4% at
      the 12th month of ETV-plus-ADV therapy. During the same time periods, ETV
      resistant mutations were present in 46.3% and 38.8%, and ADV-resistant mutations
      were present in 3.1% and 9.4% respectively. When 256 nucleotides from 32 samples
      were examined for mutations, clonal analysis detected 93 mutations (36.3%),
      direct sequencing detected 36 mutations (14.1%) and RFMP detected 73 mutations
      (28.5%). The sensitivity (73.1%, 95% CI; 64.1-82.1%) and specificity (96.9%, 95%
      CI; 94.4-99.4%) of RFMP were high, showing a concordance rate of 88.3% with the
      results from clonal analysis. All mutations exceeding 40% of the total clones
      detected by clonal analysis were also detected by RFMP. CONCLUSIONS: The clonal
      evolution of the mutation pattern in MDR HBV showed the selection of LAM
      resistant (+/-ETV-resistant) HBV during ETV rescue therapy, which may be the
      primary reason for patients' suboptimal response. Multiplex RFMP is a useful
      method for detecting MDR mutations in clinical practice.

PMID- 25872680
TI  - Children weigh the number of informants and perceptual uncertainty when
      identifying objects.
AB  - The aim of this study was to evaluate how 3- to 5-year-old children (N = 150)
      identify an object when they are confronted with conflicting evidence, notably
      when the available perceptual evidence is contradicted by the testimony of either
      a lone informant or a three-informant consensus. Results showed that (a) 5-year
      olds were more likely than 3- or 4-year-olds to rely on the perceptual evidence,
      ignoring claims made by the informants; (b) the three-informant consensus had
      more impact than a single informant for all age groups; and (c) children were
      more likely to make a perception-based response if the stimulus was perceptually
      unambiguous rather than equivocal with respect to its identity. Moreover, when
      children's task was to identify equivocal stimuli, they endorsed the three
      informant consensus more than the lone informant. In contrast, when they needed
      to identify unambiguous stimuli, the number of informants did not influence
      children's responses. Taken together, the results show that the tendency to
      resist testimony on the basis of perceptual evidence increases with age.
      Moreover, preschoolers monitor both the characteristics of their informants and
      the relative ambiguity of the perceptual stimuli when they need to weigh verbal
      testimony against perceptual evidence.

PMID- 25872681
TI  - Antibiotic activity of iron-sequestering polymers.
AB  - Increasing antibiotic resistance has compelled the development of novel
      antibiotics and adjuvant therapies that enhance the efficacy of existing
      antibiotics. Iron plays a critical role in bacterial infections, yet the use of
      iron chelators as adjuvant therapy with antibiotics has yielded highly variable
      outcomes. Multivalent polymeric materials offer an alternative approach to bind
      and sequester iron via high avidity interactions. Here, a biomimetic iron
      sequestering polymer (PAI-DHBA) was synthesized by modifying side chains of cross
      linked polyallylamine (cPAI) with 2,3-dihydroxybenzoic acid (DHBA). PAI-DHBA
      polymer gels with various DHBA contents showed high iron affinity indices and
      high selectivity for iron. The polymers showed mild antibiotic properties when
      used to treat established bacterial cultures. Pretreating culture media with PAI
      DHBA polymer, however, removed all detectable iron from media and effectively
      inhibited the growth of Pseudomonas aeruginosa. In addition, bacterial growth was
      more susceptible to antibiotics combined with PAI-DHBA. Multivalent polymers that
      bind and sequester iron, such as PAI-DHBA, offer a promising early intervention
      or adjuvant to antibiotics. 

PMID- 25872682
TI  - Pd(II)-catalyzed C(sp(3))-H arylation of amino acid derivatives with click
      triazoles as removable directing groups.
AB  - By using click-triazoles as conveniently approachable and removable directing
      groups, the direct palladium-catalyzed C(sp(3))-H arylation of amino acid
      derivatives with various aryl iodides bearing different electronic properties has
      been achieved. Notably, the desired amino acid molecule can be obtained by the
      cleavage of the tethered click-triazoles after the catalytic reaction, which aims
      to provide a practical protocol for the accessibility of both natural and
      synthetic amino acids. 

PMID- 25872683
TI  - Clustering, climate and dengue transmission.
AB  - Dengue is currently the most rapidly spreading vector-borne disease, with an
      increasing burden over recent decades. Currently, neither a licensed vaccine nor
      an effective anti-viral therapy is available, and treatment largely remains
      supportive. Current vector control strategies to prevent and reduce dengue
      transmission are neither efficient nor sustainable as long-term interventions.
      Increased globalization and climate change have been reported to influence dengue
      transmission. In this article, we reviewed the non-climatic and climatic risk
      factors which facilitate dengue transmission. Sustainable and effective
      interventions to reduce the increasing threat from dengue would require the
      integration of these risk factors into current and future prevention strategies,
      including dengue vaccination, as well as the continuous support and commitment
      from the political and environmental stakeholders. 

PMID- 25872684
TI  - Donor Age-Based Analysis of Liver Transplantation Outcomes: Short- and Long-Term
      Outcomes Are Similar Regardless of Donor Age.
AB  - BACKGROUND: The shortage of donor organs has led to increasing use of extended
      criteria donors, including older donors. The upper limit of donor age that
      produces acceptable outcomes continues to be explored. In liver transplantation,
      with appropriate selection, graft survival and patient outcomes would be
      comparable regardless of age. STUDY DESIGN: We performed a retrospective analysis
      of 1,036 adult orthotopic liver transplantations (OLT) from a prospectively
      maintained database performed between January 1, 2000 and December 31, 2013. The
      study focus group was liver transplantations performed using grafts from older
      (older than 60 years) deceased donors. Deceased donor liver transplantations done
      during the same time period using grafts from younger donors (younger than 60
      years) were analyzed for comparison. Both groups were further divided based on
      recipient age (less than 60 years and 60 years or older). Donor age was the
      primary variable. Recipient variables included were demographics, indication for
      transplantation, Model for End-Stage Liver Disease (MELD), graft survival, and
      patient survival. Operative details and postoperative complications were
      analyzed. RESULTS: Patient demographics and perioperative details were similar
      between groups. Patient and graft survival rates were similar in the 4 groups.
      Rates of rejection (p = 0.07), bile leak (p = 0.17), and hepatic artery
      thrombosis were comparable across all groups (p = 0.84). Hepatitis C virus
      recurrence was similar across all groups (p = 0.10). Thirty-one young recipients
      (less than 60 years) received grafts from donors aged 70 or older. Their survival
      and other complication rates were comparable to those in the young donor to young
      recipient group. CONCLUSIONS: Comparable outcomes in graft and patient survivals
      were achieved using older donors (60 years or more), regardless of recipient age,
      without increased rate of complications.

PMID- 25872685
TI  - Is Liver Transplantation Appropriate for Patients with Potentially Resectable De
      Novo Hilar Cholangiocarcinoma?
AB  - BACKGROUND: Liver transplantation (LTX) is curative for selected patients with
      hilar cholangiocarcinoma (HC) in the setting of sclerosing cholangitis. However,
      the outcome of LTX vs liver resection (RTX) for patients with de novo HC remains
      unclear. STUDY DESIGN: Patients with de novo HC treated by protocol LTX (n = 90)
      or RTX (n = 124) between 1993 and 2013 were reviewed. Based on preoperative
      imaging, RTX was pursued for Bismuth type III HC and LTX for unresectable Bismuth
      type IV. RESULTS: Unadjusted analysis showed that overall survival after
      operation was greater for LTX than RTX (p = 0.003). One-, 3-, and 5-year overall
      survival rates, respectively, were 90%, 71%, and 59% for LTX and 81%, 53%, and
      36% for RTX. Survival was not different between LTX and RTX after adjusting for
      patient age, lymph node metastases, and tumor size. After postoperative
      pathologic review, HC after RTX was reclassified as Bismuth-Corlette (B-C) IV,
      based on the necessity of multiple biliary anastomoses in 40 patients to more
      accurately compare treatment outcomes. Overall survival was greater after LTX
      than RTX (p = 0.039) for patients with Bismuth-Corlette IV HC. CONCLUSIONS:
      Patients with clearly resectable de novo HC should be treated with resection
      because there is no evidence that they would fare better with LTX. Patients with
      locally unresectable de novo HC, meeting criteria for our protocol, should be
      treated with LTX. The decision to proceed with RTX or LTX for patients with
      borderline resectable de novo HC remains difficult, but our results suggest that
      patients with B-C type IV HC might be best treated with transplantation, if they
      are excellent transplant candidates.

PMID- 25872686
TI  - Which Patients Require More Care after Hospital Discharge? An Analysis of Post
      Acute Care Use among Elderly Patients Undergoing Elective Surgery.
AB  - BACKGROUND: The use of post-acute care is common among the elderly and accounts
      for $62 billion in annual Medicare expenditures. However, little is known about
      post-acute care use after surgery. STUDY DESIGN: Data were merged between the
      American College of Surgeons National Surgical Quality Improvement Program (ACS
      NSQIP) and Medicare claims for 2005 to 2008. Post-acute care use, including
      skilled nursing facilities (SNF), inpatient rehabilitation facilities (IRF), and
      home health care (HHC) were analyzed for 3 operations: colectomy, pancreatectomy,
      and open abdominal aortic aneurysm repair. Controlling for both preoperative risk
      factors and the occurrence of postoperative complications, we used multinomial
      logistic regression to estimate the odds of use for each type of post-acute care
      after elective surgery compared with home discharge. RESULTS: Post-acute care was
      used frequently for patients undergoing colectomy (40.0%; total n=10,932),
      pancreatectomy (46.0%; total n=2,144), and open abdominal aortic aneurysm (AAA)
      repair (44.9%; total n=1,736). Home health was the most frequently reported post
      acute care service for each operation (range 23.2% to 31.5%) followed by SNF
      (range 12.0% to 15.0%), and then by IRF (range 2.5% to 5.4%). The majority of
      patients with at least 1 inpatient complication were discharged to post-acute
      care (range 58.6% for open AAA repair to 64.4% for colectomy). In multivariable
      analysis, specific preoperative risk factors, including advanced age, poor
      functional status, and inpatient complications were significantly associated with
      increased risk-adjusted odds of discharge to post-acute care for each operation
      studied. CONCLUSIONS: Among elderly patients, post-acute care use is frequent
      after surgery and is significantly associated with several preoperative risk
      factors and postoperative inpatient complications. Further work is needed to
      ensure that post-acute care services are used appropriately and cost-effectively.

PMID- 25872687
TI  - Surgical drainage of a small tissue volume with butterfly infusion and vacuum
      phlebotomy tube sets.

PMID- 25872688
TI  - Outcomes of Thoracic Endovascular Aortic Repair and Subclavian Revascularization
      Techniques.
AB  - BACKGROUND: Practice guidelines for management of the left subclavian artery
      (LSA) during thoracic endovascular aortic repair (TEVAR) are based on low-quality
      evidence, and there is limited literature that addresses optimal
      revascularization techniques. The purpose of this study was to compare outcomes
      of LSA coverage during TEVAR and revascularization techniques. STUDY DESIGN: We
      performed a single-center retrospective cohort study from 2001 to 2013. Patients
      were categorized by LSA revascularization and by revascularization technique,
      carotid-subclavian bypass (CSB), or subclavian-carotid transposition (SCT).
      Thirty-day and mid-term stroke, spinal cord ischemia, vocal cord paralysis, upper
      extremity ischemia, primary patency of revascularization, and mortality were
      compared. RESULTS: Eighty patients underwent TEVAR with LSA coverage, 25% (n =
      20) were unrevascularized and the remaining patients underwent CSB (n = 22
      [27.5%]) or SCT (n = 38 [47.5%]). Mean follow-up time was 24.9 months.
      Comparisons between unrevascularized and revascularized patients were significant
      for a higher rate of 30-day stroke (25% vs 2%; p = 0.003) and upper extremity
      ischemia (15% vs 0%; p = 0.014). However, there was no difference in 30-day or
      mid-term rates of spinal cord ischemia, vocal cord paralysis, or mortality. There
      were no statistically significant differences in 30-day or midterm outcomes for
      CSB vs SCT. Primary patency of revascularizations was 100%. Survival analysis
      comparing unrevascularized vs revascularized LSA was statistically significant
      for freedom from stroke and upper extremity ischemia (p = 0.02 and p = 0.003,
      respectively). After adjustment for advanced age, urgency, and coronary artery
      disease, LSA revascularization was associated with lower rates of perioperative
      adverse events (odds ratio = 0.23; p = 0.034). CONCLUSIONS: During TEVAR, LSA
      coverage without revascularization is associated with an increased risk of stroke
      and upper extremity ischemia. When LSA coverage is required during TEVAR, CSB and
      SCT are equally acceptable options.

PMID- 25872689
TI  - Surgeons in Difficulty: An Exploration of Differences in Assistance-Seeking
      Behaviors between Male and Female Surgeons.
AB  - BACKGROUND: Physician burnout is associated with diminished ability to practice
      with requisite skill and safety. Physicians are often reluctant to seek help for
      an impaired colleague or for impairment that affects their own ability to
      practice. To better support surgeons in difficulty, we explored sex differences
      in assistance-seeking behaviors under stress. STUDY DESIGN: Surgeons in 3
      national societies completed an IRB-approved anonymous multiple-choice and free
      text response survey. Responses were explored with the general linear model using
      item-specific continuous and categorical methods. STUDY DESIGN: Two hundred and
      twelve surgeons (n = 79 [37.3%] male, n = 133 [63%] female) responded. Although
      men and women worked similar hours (p > 0.05), women worked more clinical (p <
      0.01) and fewer administrative hours (p < 0.01) in later age (F = 7.88; degrees
      of freedom [df] 4/145; p < 0.01). Women were less satisfied with work-life
      balance, as identified by aggregate variables related to emotional/decisional
      partnership, non-work-related chore support, and personal fulfillment (F = 15.29;
      df 3/16; p < 0.01), but change jobs less frequently (F = 4.23; df 1/201; p <
      0.05). Males are more likely to seek help from colleagues (chi-square 107.5; p <
      0.01) or friends (chi-square 123.8; p < 0.01) and women are more likely to seek
      support from professional counselors (chi-square 146.8; p < 0.01). Almost one
      third of surgeons would ignore behaviors that adversely impact well being and
      could result in potential personal or patient safety. CONCLUSIONS: The
      differences between the assistance-seeking and reporting behaviors of male and
      female surgeons in distress could have implications for identification and
      treatment of this population. These findings can be used to develop educational
      activities to teach surgeons how to effectively handle these challenging
      situations.

PMID- 25872690
TI  - Is CT Angiography of the Head Useful in the Management of Traumatic Brain Injury?
AB  - BACKGROUND: Computed tomography angiography (CTA) has been increasingly used in
      traumatic brain injury (TBI) patients to uncover vascular lesions that might have
      preceded the trauma and caused the bleed. This study aims to evaluate the
      usefulness of head CTA in the initial care of blunt TBI patients. STUDY DESIGN:
      We conducted a retrospective case-control analysis of adult TBI patients,
      admitted to our Level I trauma center from January 1, 2012 to December 31, 2012.
      The patients were grouped as those with and without a CTA of the head. The
      primary outcomes included a change in management after the findings of head CTA
      and secondary outcomes included rate of admission to the ICU, ICU length of stay,
      hospital length of stay, discharge disposition, and mortality. RESULTS: Six
      hundred adult patients had blunt TBI and underwent head CT as a part of their
      evaluation. Of these 600 patients, 132 (22%) underwent head CTA in addition to
      CT. Only one patient had altered management after the CTA results; the patient
      had a diagnostic angiogram that was negative. Ninety-eight patients did not have
      any additional findings on CTA. Of the remaining 33 patients with additional CTA
      findings, 12 had incidental vascular malformations, which showed no acute
      pathology and were not related to the injury. In the matched comparisons,
      patients with CTA had a longer hospital stay, higher rate of ICU admission, and
      longer ICU stay. There was no significant difference in mortality and discharge
      disposition between the 2 groups. CONCLUSIONS: Head CTA is commonly used after
      blunt TBI but does not alter management and should be abandoned in the absence of
      clear indications.

PMID- 25872691
TI  - Diazoxide Cardioprotection Is Independent of Adenosine Triphosphate-Sensitive
      Potassium Channel Kir6.1 Subunit in Response to Stress.
AB  - BACKGROUND: The sarcolemmal adenosine triphosphate-sensitive potassium channel
      (sK(ATP)), composed primarily of potassium inward rectifier (Kir) 6.2 and
      sulfonylurea receptor 2A subunits, has been implicated in cardiac myocyte volume
      regulation during stress; however, it is not involved in cardioprotection by the
      adenosine triphosphate-sensitive potassium channel (K(ATP)) channel opener
      diazoxide (7-chloro-3-methyl-1,2,4-benzothiadiazine-1,1-dioxide [DZX]).
      Paradoxically, the sK(ATP) channel subunit Kir6.2 is necessary for detrimental
      myocyte swelling secondary to stress. The Kir6.1 subunit can also contribute to
      K(ATP) channels in the heart, and we hypothesized that this subunit might play a
      role in myocyte volume regulation in response to stress. STUDY DESIGN: Isolated
      cardiac myocytes from either wild-type mice or mice lacking the Kir6.1 subunit
      (Kir6.1[-/-]) were exposed to control Tyrode's solution (TYR) for 20 minutes,
      test solution (TYR, hypothermic hyperkalemic cardioplegia [CPG], or CPG + K(ATP)
      channel opener DZX [CPG + DZX]) for 20 minutes, followed by TYR for 20 minutes.
      Myocyte volume and contractility were measured and analyzed. RESULTS: Both wild
      type and Kir6.1(-/-) myocytes demonstrated substantial swelling during exposure
      to stress (CPG), which was prevented by DZX. Wild-type myocytes also demonstrated
      reduced contractility during stress of CPG that was prevented by DZX. However,
      Kir6.1(-/-) myocytes did not show reduced contractility during stress.
      CONCLUSIONS: These data indicate that K(ATP) channel subunit Kir6.1 is not
      necessary for DZX's maintenance of cell volume during the stress of CPG. The
      absence of Kir6.1 does not affect the contractile properties of myocytes during
      stress, suggesting the absence of Kir6.1 improves myocyte tolerance to stress via
      an unknown mechanism.

PMID- 25872692
TI  - Ventral Slit Scrotal Flap: A New Outpatient Surgical Option for Reconstruction of
      Adult Buried Penis Syndrome.
AB  - INTRODUCTION: We present a novel technique using ventral slit with scrotal skin
      flaps (VSSF) for the reconstruction of adult buried penis without skin grafting.
      TECHNICAL CONSIDERATIONS: An initial ventral slit is made in the phimotic ring,
      and the penis is exposed. To cover the defect in the ventral shaft skin, local
      flaps are created by making a ventral midline scrotal incision with horizontal
      relaxing incisions. The scrotal flaps are rotated to resurface the ventral shaft.
      Clinical data analyzed included preoperative diagnoses, length of stay, blood
      loss, and operative outcomes. Complications were also recorded. Fifteen
      consecutive patients with a penis trapped due to lichen sclerosus (LS) or
      phimosis underwent repair with VSSF. Each was treated in the outpatient setting
      with no perioperative complications. Mean age was 51 years (range, 26-75 years),
      and mean body mass index was 42.6 kg/m(2) (range, 29.8-53.9 kg/m(2)). The
      majority of patients (13 of 15, 87%) had a pathologic diagnosis of LS. Mean
      estimated blood loss was 57 cc (range, 25-200 cc), mean operative time was 83
      minutes (range, 35-145 minutes), and all patients were discharged on the day of
      surgery. The majority of patients (11 of 15, 73.3%) remain satisfied with their
      results and have required no further intervention. Recurrences in 3 of 15 (20.0%)
      were due to LS, panniculus migration, and concealment by edematous groin tissue;
      2 of these patients underwent subsequent successful skin grafting. CONCLUSION:
      VSSF is a versatile, safe, and effective reconstructive option in appropriately
      selected patients with buried penis, which enables reconstruction of penile shaft
      skin defects without requiring complex skin grafting.

PMID- 25872693
TI  - Does Routine Pathology Analysis of Adult Circumcision Tissue Identify Penile
      Cancer?
AB  - OBJECTIVE: To assess the utility of foreskin pathology analysis, we evaluated the
      outcomes and the costs of this practice in patients for whom penile cancer was
      not suspected. Adult circumcision specimens are routinely sent for pathologic
      analysis even when penile cancer is not suspected, increasing costs with little
      benefit. MATERIALS AND METHODS: All adult patients who underwent circumcision
      between January 2000 and August 2013 at a single institution were evaluated by
      retrospective chart review. Cases of suspected penile cancer (n = 6) were
      excluded. We identified cases where foreskin specimens were sent for pathologic
      analysis and reviewed pathology reports. Our Department of Pathology estimated
      the cost for evaluation of specimens at $311 per case. RESULTS: A total of 147
      circumcisions were performed in patients with no suspicious findings. Pathologic
      analysis was obtained in 69% (101 of 147) of the cases. Inflammation (58%) was
      the most common finding. One unsuspected instance of squamous cell carcinoma
      (Tis) was identified in a patient with human immunodeficiency virus (1 of 147 =
      0.7%). The overall cost of pathologic analysis in this study was $31,411.
      CONCLUSION: In individuals without predisposing immunodeficiency and where cancer
      was not suspected, we found that pathologic analysis of circumcision specimens
      identified no additional malignancies. Our data suggest that in this normal risk
      population, pathologic analysis may not be required. Additionally, forgoing
      pathology on foreskin specimens in lower risk cases may reduce costs to the
      health care system.

PMID- 25872694
TI  - Reply: To PMID 25872693.

PMID- 25872695
TI  - A Case of High-grade Transitional Cell Carcinoma of the Bladder in a Pediatric
      Patient With Turner Syndrome.
AB  - Transitional cell carcinoma is a rare entity in children, especially in the first
      decade of life. The majority of these tumors are of low grade and noninvasive. We
      report an interesting case of a high-grade superficial transitional cell
      carcinoma in a 3-year-old girl with Turner syndrome. 

PMID- 25872696
TI  - Partial and Radical Nephrectomy for Unilateral Synchronous Multifocal Renal
      Cortical Tumors.
AB  - OBJECTIVE: To evaluate clinicopathologic characteristics and treatment outcomes
      of patients undergoing partial nephrectomy (PN) or radical nephrectomy (RN) for
      unilateral synchronous multifocal renal tumors. METHODS: We retrospectively
      reviewed medical records for 128 patients with nonmetastatic, unilateral,
      synchronous, multifocal renal tumors who underwent surgical resection at our
      institution from 1995 to 2012. Five patients with hereditary renal cell carcinoma
      were excluded. Differences between patient and tumor characteristics from the 2
      nephrectomy groups were evaluated. Outcomes in terms of recurrence-free survival,
      overall survival, and chronic kidney disease upstaging were estimated using
      Kaplan-Meier methods. The log-rank test was used for group comparisons. RESULTS:
      The study cohort included 78 PN patients (63%) and 45 RN patients (37%); 17 of 95
      planned PN (18%) were converted to RN. Tumor diameter and RENAL nephrometry
      scores were greater in RN patients (P <.0001 and P = .0002, respectively).
      Pathologic stage T3 was seen in 40% of RN patients and 10% of PN patients (P =
      .0002). Histologic concordance was apparent in 60 of 123 patients (49%). Median
      follow-up for patients alive without a recurrence was 4 years. Five-year
      recurrence-free survival was 98% for PN and 85% for RN. Five-year overall
      survival was 96% for PN and 86% for RN (P = .5). Five-year freedom from chronic
      kidney disease upstaging was 74% for PN and 55% for RN (P = .11). CONCLUSION:
      Partial nephrectomy for the treatment of unilateral, synchronous, multifocal,
      renal tumors with favorable characteristics was associated with a low recurrence
      rate. These findings suggest PN is an appropriate management strategy for this
      group of carefully selected patients.

PMID- 25872697
TI  - Semen Quality Assessment in Fertile Men in Madrid During the Last 3 Decades.
AB  - OBJECTIVE: To evaluate semen quality of men with proven fertility in Spain over
      the last 3 decades. METHODS: We conduct a retrospective analysis of ejaculate
      samples of 992 men between 1985 and 2009. All patients had proven fertility as
      demonstrated by fathering at least 2 children and a semen analysis performed
      before they underwent vasectomy. A standardized procedure was used for the semen
      analysis. Semen volume, total sperm count, sperm concentration, motility, and
      percentage of morphologically normal spermatozoa were assessed. Mean values were
      calculated by examining microscopic fields of 100 spermatozoa. RESULTS:
      Statistically significant differences were found in all semen parameters
      analyzed. For the periods 1985-1990, 1990-2000, and 2000-2009, the mean (standard
      deviation [SD]) sperm concentration was 27.7 (22.97), 20.73 (14.79), and 20.18
      (20.79) * 10(6) (P <.0001). The mean (SD) progressive motility for each period
      was 53.19 (20.35), 47.22 (15.84), and 40.57 (15.15; P <.0001). The mean (SD)
      normal-shaped spermatozoa for each period was 67.69 (10.24), 58.87 (14.67), and
      51.02 (15.76; P <.0001). Multivariate analysis using a logistic regression model
      showed that age had no significant effect in the variation of semen parameters at
      the cut-points analyzed, except for normal forms at percentile 25 (P = .001).
      Multivariate analysis revealed a trend for decline of semen in sperm
      concentration, progressive and nonprogressive motility, and the percentage of
      morphologically normal spermatozoa (P = .001-.002). CONCLUSION: Over the last 3
      decades, a decline in semen quality was found in all the parameters analyzed in
      Spanish men with proven fertility.

PMID- 25872698
TI  - The Biocompatibility of a Cellulose Exopolysaccharide Implant in the Rabbit
      Bladder When Compared With Dextranomer Microspheres Plus Hyaluronic Acid.
AB  - OBJECTIVE: To evaluate biocompatibility of a cellulosic exopolysaccharide (CEC)
      as bulking agent in rabbit urinary bladder. MATERIALS AND METHODS: The
      experimental study was developed at the Nucleus for Experimental Surgery or UFPE.
      The new agent was injected into the bladder of the adult rabbits using a small
      abdominal incision. Animals were injected with 0.2 mL of dextranomer microspheres
      (Dx) plus hyaluronic acid and CEC. The animals were studied after 3 days (G1), 90
      days (G2), and 11 months (G3). The biocompatibility was evaluated according to
      the histologic parameters (presence of blood vessels, inflammatory reaction, and
      collagen deposition) by a quantitative analysis. The Student paired t test was
      used for continuous variables, and the scores were compared through the chi
      square test. RESULTS: Both materials were structurally homogeneous and free from
      inflammatory cells or blood vessels (G1). In 3-month samples (G2), CEC areas were
      densely invaded by fibroblasts and blood vessels. Dx areas were fragmented but
      still homogeneous and free from cells or blood vessels. Samples from 3 and 11
      months showed a significant difference in favor of CEC especially concerning
      preservation of material in the implant site, as well as the presence of
      neovascularization. This experimental study represents a positive outcome in
      terms of reflux resolution in the long term. Further studies may be necessary to
      confirm its efficacy when in clinical use. CONCLUSION: The CEC exhibited low
      inflammatory response and integrated with the host tissue better than Dx in the
      long-term follow-up.

PMID- 25872699
TI  - A Rare Case of Neonatal Alloimmune Thrombocytopenia Causing Prolonged
      Postcircumcision Bleeding.
AB  - Postcircumcision bleeding can be the presenting symptom of a coagulopathy. A
      blood dyscrasia that is known but not documented in association with circumcision
      is neonatal alloimmune thrombocytopenia (NAIT). A 2-day-old male infant presented
      with postcircumcision bleeding. Platelet count was 5000 per microliter of blood.
      The child was treated conservatively with hematoma improvement. Few studies exist
      involving patients with coagulopathies who undergo circumcision. Our patient is
      the first to present with prolonged postcircumcision bleeding as the initial
      presentation of NAIT. NAIT and other coagulopathies that present as prolonged
      postcircumcision bleeding can often be managed successfully with conservative
      management. 

PMID- 25872700
TI  - Editorial Comment.

PMID- 25872701
TI  - A rare case of cutaneous collagenous vasculopathy.
AB  - Cutaneous collagenous vasculopathy is a rare microangiopathy first described by
      Salama and Rosenthal in 2000. Several cases have been reported to date,
      describing distinct histological findings of thick hyaline collagenous blood
      vessel walls in the superficial dermis. Clinical confusion can arise with
      generalised essential telangiectasia. We report a case occurring in a 76-year-old
      woman who presented with a 2-year history of a telangiectatic rash progressing
      from her knees upwards. The diagnosis was confirmed on skin biopsy and treatment
      with pulsed dye laser was later initiated at the patient's request. 

PMID- 25872702
TI  - Development and cognitive functions in Saudi pre-school children with feeding
      problems without underlying medical disorders.
AB  - AIM: This study was conducted to assess development and cognitive functions in
      relation to growth in Saudi pre-school children with feeding problems (FPs)
      without underlying medical disorders. METHODS: Three hundred fifteen pre-school
      children with FPs (221 with normal growth (FP-N), 62 with failure to thrive (FTT)
      (FP-FTT), 32 with overweight (FP-OW)) and 100 healthy children (Ref group)
      underwent in-depth assessment by anthropometric measurements, dietetic history,
      Behavioral Pediatrics Feeding Assessment Scale, Denver Developmental Screening
      test (DDST) and Stanford Binet fifth edition intelligence scales (SB-5). RESULTS:
      The main FPs detected in Saudi children were picky eating in 85.5% of FP-N group,
      infantile anorexia and poor eating in more than 90% of FP-FTT group and
      overeating in 53% of FP-OW group. FPs were not due to evident psychosocial
      factors but were mostly related to unhealthy feeding behaviours. FP-N children
      were still having normal growth parameters, but they had significantly lower
      growth parameters than healthy children. Failed screening with DDST was only more
      significantly recorded in FP-FTT children than in Ref children (P = 0.04). The
      overall IQ value by SB-5 was significantly lower in FP-FTT group compared with FP
      N group (P = 0.01), in FP-FTT group compared with Ref group (P < 0.001) as well
      as in FP-OW group compared with Ref group (P < 0.001). CONCLUSIONS: Persistent
      FPs resulted in significant negative impact not only on growth status but also on
      developmental milestones and cognitive functions of pre-school children. Healthy
      feeding habits are mandatory to prevent serious consequences of FPs on growth and
      development of Saudi pre-school children.

PMID- 25872703
TI  - The Impact of an ECV Service is Limited by Antenatal Breech Detection: A
      Retrospective Cohort Study.
AB  - BACKGROUND: External cephalic version (ECV) reduces the chance of breech
      presentation at term birth and lowers the chance of a cesarean delivery. ECV
      services are now in place in many units in the United Kingdom but their
      effectiveness is unknown. The aim of this study was to investigate the reasons
      for breech presentation at term birth. METHODS: We performed a retrospective
      cohort study of 394 consecutive babies who were in breech presentation at term
      birth in a large United Kingdom maternity unit that offers ECV. The cohort was
      analyzed over two time periods 10 years apart: 1998-1999 and 2008-2009. RESULTS:
      Only 33.8 percent of women had undergone a (failed) ECV attempt. This low
      proportion was mainly because breech presentation was not diagnosed antenatally
      (27.9%). Other contributing factors were: ECV not offered by clinicians (12.2%),
      ECV declined by women (14%), and contraindications to ECV (10.7%). Over the 10
      year period, the proportion of breech presentations that were not diagnosed
      antenatally increased from 23.2 to 32.5 percent (p = 0.04), which constituted
      52.8 percent of women who had not undergone an ECV attempt in 2008-2009. Failure
      of clinicians to offer ECV reduced from 21.6 to 3.0 percent (p = 0.0001) and the
      proportion of women declining ECV decreased from 19.1 to 9.0 percent (p = 0.005).
      Overall, ECV attempts increased from 28.9 to 38.5 percent (p = 0.05).
      CONCLUSIONS: Although ECV counseling, referral, and attempt rates have increased,
      failure to detect breech presentation antenatally is the principal barrier to
      successful ECV. Improved breech detection would have a greater impact than
      methods to increase ECV success rates.

PMID- 25872704
TI  - Effects of temperature and composite alumina on pyrolysis of sewage sludge.
AB  - An interactive dual-circulating fluidized bed system has been proposed in which
      the pyrolysis of sewage sludge (SS) and incineration of biomass proceed
      simultaneously, and alumina is used as the bed material and heat carrier. The
      alumina coated with biomass ash would mix with sewage sludge in the pyrolysis
      reactor of this device. It is important to know the influence of composite
      alumina (CA) on the pyrolysis progress. Sewage sludge was pyrolyzed in a fixed
      bed reactor from 400 to 600 degrees C using CA as catalyst. The effects of
      temperature and CA additive ratio on the products were investigated. The product
      yields and component distribution of non-condensable gas were more sensitive to
      the change of temperature, and the maximum liquid yield of 48.44 wt.% and maximum
      Useable Energy of Liquid of 3871 kJ/kg sludge were observed at 500 degrees C with
      1/5 CA/SS (mass ratio). The gas chromatography-mass spectrometry results showed
      that the increase of temperature enhanced devolatilization of organic matter and
      promoted cyclization and aromatization of aliphatics. The presence of CA could
      strengthen secondary cracking and interaction among primary products from
      different organic compounds, such as acid-amine condensation, and reduce the
      content of oxygenated compounds. When the CA additive amount exceeded a certain
      proportion, the aromatization was clearly strengthened. The effects of CA on
      decomposition of fatty acids and formation of aromatics were similar to that of
      temperature. This means that the reaction temperature could be lowered by
      introducing CA, which has a positive effect on reducing energy consumption.

PMID- 25872705
TI  - Numerical study of the effects of local atmospheric circulations on a pollution
      event over Beijing-Tianjin-Hebei, China.
AB  - Currently, the Chinese central government is considering plans to build a
      trilateral economic sphere in the Bohai Bay area, including Beijing, Tianjin and
      Hebei (BTH), where haze pollution frequently occurs. To achieve sustainable
      development, it is necessary to understand the physical mechanism of the haze
      pollution there. Therefore, the pollutant transport mechanisms of a haze event
      over the BTH region from 23 to 24 September 2011 were studied using the Weather
      Research and Forecasting model and the FLEXible-PARTicle dispersion model to
      understand the effects of the local atmospheric circulations and atmospheric
      boundary layer structure. Results suggested that the penetration by sea-breeze
      could strengthen the vertical dispersion by lifting up the planetary boundary
      layer height (PBLH) and carry the local pollutants to the downstream areas; in
      the early night, two elevated pollution layers (EPLs) may be generated over the
      mountain areas: the pollutants in the upper EPL at the altitude of 2-2.5 km were
      favored to disperse by long-range transport, while the lower EPL at the altitude
      of 1 km may serve as a reservoir, and the pollutants there could be transported
      downward and contribute to the surface air pollution. The intensity of the sea
      land and mountain-valley breeze circulations played an important role in the
      vertical transport and distribution of pollutants. It was also found that the
      diurnal evolution of the PBLH is important for the vertical dispersion of the
      pollutants, which is strongly affected by the local atmospheric circulations and
      the distribution of urban areas.

PMID- 25872706
TI  - Removal kinetics of phosphorus from synthetic wastewater using basic oxygen
      furnace slag.
AB  - Removal kinetics of phosphorus through use of basic oxygen furnace slag (BOF
      slag) was investigated through batch experiments. Effects of several parameters
      such as initial phosphorus concentration, temperature, BOF-slag size, initial pH,
      and BOF-slag dosage on phosphorus removal kinetics were measured in detail. It
      was demonstrated that the removal process of phosphorus through BOF-slag followed
      pseudo-first-order reaction kinetics. The apparent rate constant (kobs)
      significantly decreased with increasing initial phosphorus concentration, BOF
      slag size, and initial pH, whereas it exhibited an opposite trend with increasing
      reaction temperature and BOF-slag dosage. A linear dependence of kobs on total
      removed phosphorus (TRP) was established with kobs=(3.51+/-0.11)*10(-4)*TRP.
      Finally, it was suggested that the Langmuir-Rideal (L-R) or Langmuir-Hinshelwood
      (L-H) mechanism may be used to describe the removal process of phosphorus using
      BOF-slag. 

PMID- 25872707
TI  - Application of constructed wetlands for wastewater treatment in tropical and
      subtropical regions (2000-2013).
AB  - Constructed wetlands (CWs) have been successfully used for treating various
      wastewaters for decades and have been identified as a sustainable wastewater
      management option for developing countries. With the goal of promoting
      sustainable engineered systems that support human well-being but are also
      compatible with sustaining natural (environmental) systems, the application of
      CWs has become more relevant. Such application is especially significant for
      developing countries with tropical climates, which are very conducive to higher
      biological activity and productivity, resulting in higher treatment efficiencies
      compared to those in temperate climates. This paper therefore highlights the
      practice, applications, and research of treatment wetlands under tropical and
      subtropical conditions since 2000. In the present review, removal of biochemical
      oxygen demand (BOD) and total suspended solid (TSS) was shown to be very
      efficient and consistent across all types of treatment wetlands. Hybrid systems
      appeared more efficient in the removal of total suspended solid (TSS) (91.3%),
      chemical oxygen demand (COD) (84.3%), and nitrogen (i.e., 80.7% for ammonium
      (NH)4-N, 80.8% for nitrate (NO)3-N, and 75.4% for total nitrogen (TN)) as
      compared to other wetland systems. Vertical subsurface flow (VSSF) CWs removed
      TSS (84.9%), BOD (87.6%), and nitrogen (i.e., 66.2% for NH4-N, 73.3% for NO3-N,
      and 53.3% for TN) more efficiently than horizontal subsurface flow (HSSF) CWs,
      while HSSF CWs (69.8%) showed better total phosphorus (TP) removal compared to
      VSSF CWs (60.1%). Floating treatment wetlands (FTWs) showed comparable removal
      efficiencies for BOD (70.7%), NH4-N (63.6%), and TP (44.8%) to free water surface
      (FWS) CW systems. 

PMID- 25872708
TI  - Stepwise multiple regression method of greenhouse gas emission modeling in the
      energy sector in Poland.
AB  - The energy sector in Poland is the source of 81% of greenhouse gas (GHG)
      emissions. Poland, among other European Union countries, occupies a leading
      position with regard to coal consumption. Polish energy sector actively
      participates in efforts to reduce GHG emissions to the atmosphere, through a
      gradual decrease of the share of coal in the fuel mix and development of
      renewable energy sources. All evidence which completes the knowledge about issues
      related to GHG emissions is a valuable source of information. The article
      presents the results of modeling of GHG emissions which are generated by the
      energy sector in Poland. For a better understanding of the quantitative
      relationship between total consumption of primary energy and greenhouse gas
      emission, multiple stepwise regression model was applied. The modeling results of
      CO2 emissions demonstrate a high relationship (0.97) with the hard coal
      consumption variable. Adjustment coefficient of the model to actual data is high
      and equal to 95%. The backward step regression model, in the case of CH4
      emission, indicated the presence of hard coal (0.66), peat and fuel wood (0.34),
      solid waste fuels, as well as other sources (-0.64) as the most important
      variables. The adjusted coefficient is suitable and equals R2=0.90. For N2O
      emission modeling the obtained coefficient of determination is low and equal to
      43%. A significant variable influencing the amount of N2O emission is the peat
      and wood fuel consumption.

PMID- 25872709
TI  - Abatement of SO2-NOx binary gas mixtures using a ferruginous active absorbent:
      Part I. Synergistic effects and mechanism.
AB  - A novel ferruginous active absorbent, prepared by fly ash, industrial lime and
      the additive Fe(VI), was introduced for synchronous abatement of binary mixtures
      of SO2-NOx from simulated coal-fired flue gas. The synergistic action of various
      factors on the absorption of SO2 and NOx was investigated. The results show that
      a strong synergistic effect exists between Fe(VI) dose and reaction temperature
      for the desulfurization. It was observed that in the denitration process, the
      synergy of Fe(VI) dose and Ca/(S+N) had the most significant impact on the
      removal of NO, followed by the synergy of Fe(VI) and reaction temperature, and
      then the synergy of reaction temperature and flue gas humidity. A scanning
      electron microscope (SEM) and an accessory X-ray energy spectrometer (EDS) were
      used to observe the surface characteristics of the raw and spent absorbent as
      well as fly ash. A reaction mechanism was proposed based on chemical analysis of
      sulfur and nitrogen species concentrations in the spent absorbent. The Gibbs free
      energy, equilibrium constants and partial pressures of the SO2-NOx binary system
      were determined by thermodynamics. 

PMID- 25872710
TI  - Adsorption of benzene, cyclohexane and hexane on ordered mesoporous carbon.
AB  - Ordered mesoporous carbon (OMC) with high specific surface area and large pore
      volume was synthesized and tested for use as an adsorbent for volatile organic
      compound (VOC) disposal. Benzene, cyclohexane and hexane were selected as typical
      adsorbates due to their different molecular sizes and extensive utilization in
      industrial processes. In spite of their structural differences, high adsorption
      amounts were achieved for all three adsorbates, as the pore size of OMC is large
      enough for the access of these VOCs. In addition, the unusual bimodal-like pore
      size distribution gives the adsorbates a higher diffusion rate compared with
      conventional adsorbents such as activated carbon and carbon molecular sieve.
      Kinetic analysis suggests that the adsorption barriers mainly originated from the
      difficulty of VOC vapor molecules entering the pore channels of adsorbents.
      Therefore, its superior adsorption ability toward VOCs, together with a high
      diffusion rate, makes the ordered mesoporous carbon a promising potential
      adsorbent for VOC disposal. 

PMID- 25872711
TI  - Flux characteristics of total dissolved iron and its species during extreme
      rainfall event in the midstream of the Heilongjiang River.
AB  - The occurrence of extreme rainfall events and associated flooding has been
      enhanced due to climate changes, and is thought to influence the flux of total
      dissolved iron (TDI) in rivers considerably. Since TDI is a controlling factor in
      primary productivity in marine ecosystems, alteration of riverine TDI input to
      the ocean may lead to climate change via its effect on biological productivity.
      During an extreme rainfall event that arose in northeastern China in 2013, water
      samples were collected in the midstream of the Heilongjiang River to analyze the
      concentration and species of TDI as well as other basic parameters. The
      speciation of TDI was surveyed by filtration and ultrafiltration methods.
      Compared with data monitored from 2007 to 2012, the concentration of TDI
      increased significantly during this event, with an average concentration of 1.11
      mg/L, and the estimated TDI flux reached 1.2*10(5) tons, equaling the average
      annual TDI flux level. Species analysis revealed that low-molecular-weight
      complexed iron was the dominant species, and the impulse of TDI flux could
      probably be attributed to the hydrological connection to riparian wetlands and
      iron-rich terrestrial runoff. Moreover, dissolved organic matter played a key
      role in the flux, species and bioavailability of TDI. In addition, there is a
      possibility that the rising TDI flux could further influence the transport and
      cycling of nutrients and related ecological processes in the river, estuary
      coupled with the coastal ecosystems, which merits closer attention in the future.

PMID- 25872712
TI  - Sodium fluoride induces apoptosis through reactive oxygen species-mediated
      endoplasmic reticulum stress pathway in Sertoli cells.
AB  - Excessive fluoride exposure is known to contribute to reproductive system
      dysfunction, ultimately leading to pathological damage and apoptosis in cells.
      Although both oxidative and endoplasmic reticulum (ER) stresses have been
      implicated in fluorosis, the signaling pathways and their roles in sodium
      fluoride (NaF)-induced apoptosis of Sertoli cells have been sparsely described.
      In this study, oxidative damage, ER stress, and apoptosis were analyzed after
      Sertoli cells were treated with varying doses of NaF for 24hr. Moreover, the
      antioxidant N-acetylcysteine (NAC) and pro-apoptotic transcription factor CHOP
      knockdown were used to clarify the precise interplay between reactive oxygen
      species (ROS), ER stress and their roles in NaF-induced apoptosis in Sertoli
      cells. The present study indicated that NaF significantly decreased cell
      viability and induced apoptosis in Sertoli cells. In addition, NaF exposure
      facilitated the accumulation of ROS and increased nuclear translocation of
      nuclear factor erythroid 2-related factor 2 (Nrf2) in Sertoli cells. Treatment
      with NAC caused remarkable recovery from these NaF-induced responses. Meanwhile,
      excessive NaF triggered ER stress as evidenced by up-regulated glucose-regulated
      protein 78 kDa (GRP78), PKR-like ER kinase (PERK), phosphorylation of eukaryotic
      translation initiation factor 2alpha (p-eIF2alpha) and CCAAT/enhancer-binding
      protein-homologous protein (CHOP), without affecting total eukaryotic translation
      initiation factor 2alpha (eIF2alpha). NAC effectively blocked the activation of
      ER stress, suggesting that NaF-induced ROS is an early event that triggers ER
      stress. Taken together, the results demonstrate that the ROS-mediated ER stress
      pathway is the crucial mechanistic event involved in NaF-induced apoptosis of
      Sertoli cells.

PMID- 25872713
TI  - Roles of SO2 oxidation in new particle formation events.
AB  - The oxidation of SO2 is commonly regarded as a major driver for new particle
      formation (NPF) in the atmosphere. In this study, we explored the connection
      between measured mixing ratio of SO2 and observed long-term (duration>3 hr) and
      short-term (duration<1.5 hr) NPF events at a semi-urban site in Toronto. Apparent
      NPF rates (J30) showed a moderate correlation with the concentration of sulfuric
      acid ([H2SO4]) calculated from the measured mixing ratio of SO2 in long-term NPF
      events and some short-term NPF events (Category I) (R2=0.66). The exponent in the
      fitting line of J30~[H2SO4]n in these events was 1.6. It was also found that SO2
      mixing ratios varied a lot during long-term NPF events, leading to a significant
      variation of new particle counts. In the SO2-unexplained short-term NPF events
      (Category II), analysis showed that new particles were formed aloft and then
      mixed down to the ground level. Further calculation results showed that sulfuric
      acid oxidized from SO2 probably made a negligible contribution to the growth of
      >10 nm new particles.

PMID- 25872714
TI  - Biological treatment of fish processing wastewater: A case study from Sfax City
      (Southeastern Tunisia).
AB  - The present work presents a study of the biological treatment of fish processing
      wastewater at salt concentration of 55 g/L. Wastewater was treated by both
      continuous stirred-tank reactor (CSTR) and membrane bioreactor (MBR) during 50
      and 100 days, respectively. These biological processes involved salt-tolerant
      bacteria from natural hypersaline environments at different organic loading rates
      (OLRs). The phylogenetic analysis of the corresponding excised DGGE bands has
      demonstrated that the taxonomic affiliation of the most dominant species includes
      Halomonadaceae and Flavobacteriaceae families of the Proteobacteria (Gamma
      proteobacteria class) and the Bacteroidetes phyla, respectively. The results of
      MBR were better than those of CSTR in the removal of total organic carbon with
      efficiencies from 97.9% to 98.6%. Nevertheless, salinity with increasing OLR
      aggravates fouling that requires more cleaning for a membrane in MBR while leads
      to deterioration of sludge settleability and effluent quality in CSTR.

PMID- 25872715
TI  - Mini-review on river eutrophication and bottom improvement techniques, with
      special emphasis on the Nakdong River.
AB  - Water quality in rivers is vital to humans and to maintenance of biotic and
      ecological integrity. During the Four Major Rivers restoration of South Korea,
      remarkable attempts have been made to decrease external nutrient loads and
      moveable weirs were designed to discharge silt that may deposit in pools.
      However, recently eutrophication of the Nakdong River, which was limited to the
      lower reaches, is seen to be spreading upstream. The reduction of external
      nutrient loads to rivers is a long-term goal that is unlikely to lead to
      reductions in algal blooms for many years because of the time required to
      implement effective land management strategies. It would therefore be desirable
      to implement complementary strategies. Regulating the amount of water released is
      effective at preventing algae blooms in weir pools; so, the relationship between
      discharge, stratification and bloom formation should be understood in this
      regard. However, pollutants are likely to accumulate in the riverbed upstream
      from release points. Thus, to control phosphorus levels, total phosphorus density
      should be lowered by applying in-river techniques as well. As many ecosystem
      properties are controlled by multiple processes, simultaneous river bottom
      improvement techniques, such as combined dissolved oxygen supply and nutrient
      inactivation, are likely to be effective. The purpose of this review is to
      present a series of technological approaches that can be used to improve the
      river bottom area and hence sediment nutrient release, and to illustrate the
      application of these techniques to the Nakdong River. 

PMID- 25872716
TI  - Bioreduction of vanadium (V) in groundwater by autohydrogentrophic bacteria:
      Mechanisms and microorganisms.
AB  - As one of the transition metals, vanadium (V) (V(V)) in trace amounts represents
      an essential element for normal cell growth, but becomes toxic when its
      concentration is above 1mg/L. V(V) can alter cellular differentiation, gene
      expression, and other biochemical and metabolic phenomena. A feasible method to
      detoxify V(V) is to reduce it to V(IV), which precipitates and can be readily
      removed from the water. The bioreduction of V(V) in a contaminated groundwater
      was investigated using autohydrogentrophic bacteria and hydrogen gas as the
      electron donor. Compared with the previous organic donors, H2 shows the
      advantages as an ideal electron donor, including nontoxicity and less production
      of excess biomass. V(V) was 95.5% removed by biochemical reduction when
      autohydrogentrophic bacteria and hydrogen were both present, and the reduced
      V(IV) precipitated, leading to total-V removal. Reduction kinetics could be
      described by a first-order model and were sensitive to pH and temperature, with
      the optimum ranges of pH7.5-8.0 and 35-40 degrees C, respectively. Phylogenetic
      analysis by clone library showed that the dominant species in the experiments
      with V(V) bioreduction belonged to the beta-Proteobacteria. Previously known V(V)
      reducing species were absent, suggesting that V(V) reduction was carried out by
      novel species. Their selective enrichment during V(V) bioreduction suggests that
      Rhodocyclus, a denitrifying bacterium, and Clostridium, a fermenter known to
      carry out metal reduction, were responsible for V(V) bioreduction. 

PMID- 25872717
TI  - Rice: Reducing arsenic content by controlling water irrigation.

PMID- 25872718
TI  - Apportioning aldehydes: Quantifying industrial sources of carbonyls.

PMID- 25872719
TI  - Laccase-catalyzed bisphenol A oxidation in the presence of 10-propyl sulfonic
      acid phenoxazine.
AB  - The kinetics of the Coriolopsis byrsina laccase-catalyzed bisphenol A (BisA)
      oxidation was investigated in the absence and presence of electron-transfer
      mediator 3-phenoxazin-10-yl-propane-1-sulfonic acid (PPSA) at pH5.5 and 25
      degrees C. It was shown that oxidation rate of the hardly degrading compound BisA
      increased in the presence of the highly reactive substrate PPSA. The increase of
      reaction rate depends on PPSA and BisA concentrations as well on their ratio,
      e.g., at 0.2 mmol/L of BisA and 2 MUmol/L of PPSA the rate increased 2 times. The
      kinetic data were analyzed using a scheme of synergistic laccase-catalyzed BisA
      oxidation. The calculated constant, characterizing reactivity of PPSA with
      laccase, is almost 1000 times higher than the constant, characterizing reactivity
      of BisA with laccase. This means that mediator-assisted BisA oxidation rate can
      be 1000 times higher in comparison to non-mediator reaction if compounds
      concentration is equal but very low.

PMID- 25872720
TI  - Spatial heterogeneity of lake eutrophication caused by physiogeographic
      conditions: An analysis of 143 lakes in China.
AB  - In order to identify the effect of geographic characteristics on the variations
      of nutrient concentrations and the utilization efficiency of nutrients by
      phytoplankton, data from 143 lakes, from 2008 to 2010, including three very
      different types of topography, i.e., the first topography ladder (FTL), second
      topography ladder (STL), and third topography ladder (TTL), were statistically
      analyzed. Lakes in the FTL and STL, located at high elevation (above 1000 m) and
      low longitudes (lower than 105 degrees  E), were sporadically oligotrophic,
      whereas lakes in the TTL were almost all mesotrophic and eutrophic. The trophic
      level index (TLI) became higher with the rise of longitude. Two turning points (5
      and 15 degrees C) on the curve of TLI as function of the average annual
      temperature (AAT) corresponded with the AAT in different lake regions in the STL
      and TTL. Because the responses of TLI to AAT differ significantly, there were
      variations of nutrient and algal biomass concentrations in different lake regions
      in the same type of topography ladder. According to the differences in
      utilization efficiency of total nitrogen or total phosphorus by phytoplankton,
      China could be partitioned into six lake regions. Scientific nutrient criteria
      for each lake region shall be established considering these differences in China.

PMID- 25872721
TI  - Anaerobic biodegradation of PAHs in mangrove sediment with amendment of NaHCO3.
AB  - Mangrove sediment is unique in chemical and biological properties. Many of them
      suffer polycyclic aromatic hydrocarbon (PAH) contamination. However, the study on
      PAH biological remediation for mangrove sediment is deficient. Enriched PAH
      degrading microbial consortium and electron acceptor amendment are considered as
      two effective measures. Compared to other electron acceptors, the study on CO2,
      which is used by methanogens, is still seldom. This study investigated the effect
      of NaHCO3 amendment on the anaerobic biodegradation of four mixed PAHs, namely
      fluorene (Fl), phenanthrene (Phe), fluoranthene (Flua) and pyrene (Pyr), with or
      without enriched PAH-degrading microbial consortium in mangrove sediment slurry.
      The trends of various parameters, including PAH concentrations, microbial
      population size, electron-transport system activities, electron acceptor and
      anaerobic gas production were monitored. The results revealed that the
      inoculation of enriched PAH-degrading consortium had a significant effect with
      half lives shortened by 7-13 days for 3-ring PAHs and 11-24 days for 4-ring PAHs.
      While NaHCO3 amendment did not have a significant effect on the biodegradation of
      PAHs and other parameters, except that CO2 gas in the headspace of experimental
      flasks was increased. One of the possible reasons is that mangrove sediment
      contains high concentrations of other electron acceptors which are easier to be
      utilized by anaerobic bacteria, the other one is that the anaerobes in mangrove
      sediment can produce enough CO2 gas even without adding NaHCO3.

PMID- 25872722
TI  - Achieving nitritation at low temperatures using free ammonia inhibition on
      Nitrobacter and real-time control in an SBR treating landfill leachate.
AB  - Free ammonia (FA) inhibition on nitrite-oxidized bacteria (NOB) and real-time
      control are used to achieve nitrogen removal from landfill leachate via nitrite
      pathway at low temperatures in sequencing batch reactor. The inhibition of FA on
      NOB activity during the aerobic period was prolonged using real-time control. The
      degree of nitrite accumulation was monitored along with variations of the ammonia
      oxidizing bacteria and NOB population using fluorescence in situ hybridization
      techniques. It is demonstrated that the end-point of ammonia oxidization is
      detected from the on-line measured dissolved oxygen, oxidization-reduction
      potential, and pH signals, which could avoid the loss the FA inhibition on NOB
      caused by excess aeration. At low temperature (13.0-17.6 degrees C), the level of
      nitrite pathway rapidly increased from 19.8% to 90%, suggesting that nitritation
      was successfully started up at low temperature by applying syntrophic association
      of the FA inhibition and real-time control, and then this high level of nitrite
      pathway was stably maintained for as long as 233 days. Mechanism analysis shows
      that the establishment of nitritation was primarily the result of predominant
      ammonia-oxidizing bacteria developed in the nitrifying bacteria population
      compared to NOB. This was mainly due to a gradual reduction of nitrite amount
      that is available to provide energy for the growth of NOB, eventually leading to
      the elimination of NOB from the bacterial clusters in sequencing batch reactor
      sludge system.

PMID- 25872723
TI  - Kinetics of Solvent Blue and Reactive Yellow removal using microwave radiation in
      combination with nanoscale zero-valent iron.
AB  - We investigated the efficiency and kinetics of the degradation of soluble dyes
      over the pH range 5.0-9.0 using a method employing microwave radiation in
      combination with nanoscale zero-valent iron (MW-nZVI). The nZVI particles (40-70
      nm in diameter) were prepared by a liquid-phase chemical reduction method
      employing starch as a dispersant. Compared to the removal of Solvent Blue 36 and
      Reactive Yellow K-RN using only nZVI, more rapid and efficient dye removal and
      total organic carbon removal were achieved using MW-nZVI. The dye removal
      efficiency increased significantly with decreasing pH, but was negligibly
      affected by variation in the microwave power. The kinetics of dye removal by MW
      nZVI followed both an empirical equation and the pseudo first-order model, while
      the kinetics of dye removal using nZVI could only be described by an empirical
      equation. It was also concluded that microwave heating of the dye solutions as
      well as acceleration of corrosion of nZVI and consumption of Fe(II) were possible
      reasons behind the enhanced dye degradation.

PMID- 25872724
TI  - Environmental impacts of a large-scale incinerator with mixed MSW of high water
      content from a LCA perspective.
AB  - Large-scale incinerators are applied widely as a result of the heavy burden of
      municipal solid waste (MSW) generated, while strong opposition is arising from
      the public living nearby. A large-scale working incineration plant of 1500
      ton/day was chosen for evaluation using life cycle assessment. It was found that
      the corresponding human toxicity impacts via soil (HTs), human toxicity impacts
      via water (HTw) and human toxicity impacts via air (HTa) categories are 0.213,
      2.171, and 0.012 personal equivalents (PE), and global warming (GW100) and
      nutrient enrichment (NE) impacts are 0.002 and 0.001 PE per ton of waste burned
      for this plant. Heavy metals in flue gas, such as Hg and Pb, are the two dominant
      contributors to the toxicity impact categories, and energy recovery could reduce
      the GW100 and NE greatly. The corresponding HTs, HTw and HTa decrease to 0.087,
      0.911 and 0.008 PE, and GW100 turns into savings of -0.007 PE due to the increase
      of the heating value from 3935 to 5811 kJ/kg, if a trommel screener of 40 mm mesh
      size is used to pre-separate MSW. MSW sorting and the reduction of water content
      by physical pressure might be two promising pre-treatment methods to improve the
      combustion performance, and the application of stricter standards for leachate
      discharge and the flue gas purification process are two critical factors for
      improvement of the environmental profile identified in this work.

PMID- 25872725
TI  - Quantitative structure-biodegradability relationships for biokinetic parameter of
      polycyclic aromatic hydrocarbons.
AB  - Prediction of the biodegradability of organic pollutants is an ecologically
      desirable and economically feasible tool for estimating the environmental fate of
      chemicals. In this paper, stepwise multiple linear regression analysis method was
      applied to establish quantitative structure biodegradability relationship (QSBR)
      between the chemical structure and a novel biodegradation activity index (qmax)
      of 20 polycyclic aromatic hydrocarbons (PAHs). The frequency B3LYP/6-311+G(2df,p)
      calculations showed no imaginary values, implying that all the structures are
      minima on the potential energy surface. After eliminating the parameters which
      had low related coefficient with qmax, the major descriptors influencing the
      biodegradation activity were screened to be Freq, D, MR, EHOMO and ToIE. The
      evaluation of the developed QSBR mode, using a leave-one-out cross-validation
      procedure, showed that the relationships are significant and the model had good
      robustness and predictive ability. The results would be helpful for understanding
      the mechanisms governing biodegradation at the molecular level. 

PMID- 25872726
TI  - Serious BTEX pollution in rural area of the North China Plain during winter
      season.
AB  - Atmospheric BTEX compounds (benzene, toluene, ethylbenzene and xylenes) in a
      rural site of the North China Plain (NCP) were preliminarily investigated in
      winter, and the outdoor concentrations (25.8-236.0 MUg/m3) were found to be much
      higher than those reported in urban regions. The pollution of BTEX inside a
      farmer's house was even more serious, with combined concentrations of 254.5
      1552.9 MUg/m3. Based on the ratio of benzene to toluene (1.17+/-0.34) measured,
      the serious BTEX pollution in the rural site was mainly ascribed to domestic coal
      combustion for heating during the winter season. With the enhancement of farmers'
      incomes in recent years, coal consumption by farmers in the NCP is rapidly
      increasing to keep their houses warm, and hence the serious air pollution in
      rural areas of the NCP during winter, including BTEX, should be paid great
      attention.

PMID- 25872727
TI  - Chemical composition and physical properties of filter fly ashes from eight grate
      fired biomass combustion plants.
AB  - For the handling, treatment and utilization of fly ash from biomass combustion
      its chemical composition and physical properties are important. In this study
      eight filter fly ashes from different grate-fired biomass combustion plants were
      investigated. In fly ash from straw combustion high concentrations of (K) were
      found, whereas in the fly ash from wood combustion the concentrations of Ca and
      Mg were higher. The average concentration of PO4(3-) was similar in both types of
      fly ashes. In all wood fly ashes some measured heavy metal concentrations were
      above the limits for utilization. The straw fly ashes were much less contaminated
      and can be utilized. For wood fly ash most parameters showed little variation,
      except from one fly ash where the dust pre-separator is in poor condition. The
      average values were: mass median diameter 4.3+/-0.8 MUm, spread of particle size
      distribution 19+/-11, particle density 2620+/-80 kg/m3 and angle of repose 50
      degrees +/-1 degrees . The density of the straw fly ashes is lower (2260+/-80
      kg/m3) and the spread of the size distribution is higher (72+/-24). For one straw
      combustion fly ash the values of the mass median diameter and the angle of repose
      were similar to the values of wood combustion fly ash, for the other straw fly
      ash the values differed considerably. While the particle size of this fly ash was
      much smaller, surprisingly the angle of repose was also lower. This can be
      attributed to the formation of small agglomerates in this fly ash, which were not
      disintegrated without a certain stress.

PMID- 25872728
TI  - Assessment of the sources and transformations of nitrogen in a plain river
      network region using a stable isotope approach.
AB  - The great spatial and temporal variability in hydrological conditions and
      nitrogen (N) processing introduces large uncertainties to the identification of N
      sources and quantifying N cycles in plain river network regions. By combining
      isotopic data with chemical and hydrologic measurements, we determined the
      relative importance of N sources and biogeochemical N processes in the Taige
      River in the East Plain Region of China. The river was polluted more seriously by
      anthropogenic inputs in winter than in summer. Manure and urban sewage effluent
      were the main nitrate (NO3-) sources, with the nitrification of N-containing
      organic materials serving as another important source of NO3-. In the downstream,
      with minor variations in hydrological conditions, nitrification played a more
      important role than assimilation for the decreasing ammonium (NH4+-N)
      concentrations. The N isotopic enrichment factors (epsilon) during NH4+
      utilization ranged from -13.880/00 in March to -29.000/00 in July. The ratio of
      the increase in delta18O and delta15N of river NO3- in the downstream was 1.04 in
      January and 0.92 in March. This ratio indicated that NO3- assimilation by
      phytoplankton was responsible for the increasing delta15N and delta18O values of
      NO3- in winter. The relationships between delta15N of particulate organic
      nitrogen and isotopic compositions of dissolved inorganic nitrogen indicated that
      the phytoplankton in the Taige River probably utilized NH4+ preferentially and
      mainly in summer, while in winter, NO3- assimilation by phytoplankton was
      dominant.

PMID- 25872729
TI  - The performance of a combined nitritation-anammox reactor treating anaerobic
      digestion supernatant under various C/N ratios.
AB  - A combined nitritation-anammox reactor was developed to treat the digestion
      supernatant under various C/N ratios. Due to the difficulties for heterotroph to
      utilize the refractory organics, the reactor presented relatively stable
      performance with increasing supernatant addition. Nevertheless, the adverse
      effects of supernatant would accumulate during the long-term operation and thus
      weakened the activity and shock resistance of microbes, which further led to the
      gradual decrease of reactor performance after 92 days' operation. Under this
      circumstance, supernatant with volatile fatty acids (VFAs) residuals was further
      introduced into the reactor to investigate the performance of combined
      nitritation-anammox process with VFA addition. With the appearance of VFAs, the
      nitrogen removal performance gradually restored and the reactor finally achieved
      stable and efficient performance with C/N ratio of 0.35. The VFA residuals within
      150 mg/L in the supernatant served as the extra electron donors and stimulated
      the heterotrophic denitrification process, which was vital for the enhancement of
      reactor. The nitrogen removal rate and total nitrogen removal efficiency reached
      0.49 kg N/(m3.day) and 88.8% after 140 days' operation, respectively. The
      combined nitritation-anammox reactor was proved suitable to treat digestion
      supernatant.

PMID- 25872730
TI  - Coagulation behavior and floc properties of compound bioflocculant-polyaluminum
      chloride dual-coagulants and polymeric aluminum in low temperature surface water
      treatment.
AB  - This study was intended to compare coagulation behavior and floc properties of
      two dual-coagulants polyaluminum chloride-compound bioflocculant (PAC-CBF) (PAC
      dose first) and compound bioflocculant-polyaluminum chloride (CBF-PAC) (CBF dose
      first) with those of PAC alone in low temperature drinking water treatment.
      Results showed that dual-coagulants could improve DOC removal efficiency from 30%
      up to 34%. Moreover, CBF contributed to the increase of floc size and growth
      rate, especially those of PAC-CBF were almost twice bigger than those of PAC.
      However, dual-coagulants formed looser and weaker flocs with lower breakage
      factors in which fractal dimension of PAC-CBF flocs was low which indicates a
      looser floc structure. The floc recovery ability was in the following order: PAC
      CBF>PAC alone>CBF-PAC. The flocculation mechanism of PAC was charge
      neutralization and enmeshment, meanwhile the negatively charged CBF added
      absorption and bridging effect.

PMID- 25872731
TI  - Accumulation and elimination of iron oxide nanomaterials in zebrafish (Danio
      rerio) upon chronic aqueous exposure.
AB  - A 52-day continuous semi-static waterborne exposure (test media renewed daily)
      regimen was employed to investigate the accumulation and elimination profiles of
      two iron oxide nanomaterials (nano-Fe2O3 and nano-Fe3O4) in zebrafish (Danio
      rerio). Adult zebrafish were exposed to nanomaterial suspensions with initial
      concentrations of 4.0 and 10.0 mg/L for 28 days and then were moved to clean
      water for 24 days to perform the elimination experiment. Fe content was measured
      in fish body and feces to provide data on accumulation and elimination of the two
      iron oxide nanomaterials in zebrafish. The experiment revealed that: (1) high
      accumulation of nano-Fe2O3 and nano-Fe3O4 were found in zebrafish, with maximum
      Fe contents, respectively, of 1.32 and 1.25 mg/g for 4.0 mg/L treatment groups
      and 1.15 and 0.90 mg/g for 10.0 mg/L treatment groups; (2) accumulated
      nanoparticles in zebrafish can be eliminated efficiently (the decrease of body
      burden of Fe conforms to a first-order decay equation) when fish were moved to
      nanoparticle-free water, and the elimination rates ranged from 86% to 100% by 24
      days post-exposure; and (3) according to analysis of Fe content in fish excrement
      in the elimination phase, iron oxide nanomaterials may be adsorbed via the
      gastrointestinal tract, and stored for more than 12days.

PMID- 25872732
TI  - Impact of industrial effluent on growth and yield of rice (Oryza sativa L.) in
      silty clay loam soil.
AB  - Degradation of soil and water from discharge of untreated industrial effluent is
      alarming in Bangladesh. Therefore, buildup of heavy metals in soil from
      contaminated effluent, their entry into the food chain and effects on rice yield
      were quantified in a pot experiment. The treatments were comprised of 0, 25%,
      50%, 75% and 100% industrial effluents applied as irrigation water. Effluents,
      initial soil, different parts of rice plants and post-harvest pot soil were
      analyzed for various elements, including heavy metals. Application of elevated
      levels of effluent contributed to increased heavy metals in pot soils and rice
      roots due to translocation effects, which were transferred to rice straw and
      grain. The results indicated that heavy metal toxicity may develop in soil
      because of contaminated effluent application. Heavy metals are not biodegradable,
      rather they accumulate in soils, and transfer of these metals from effluent to
      soil and plant cells was found to reduce the growth and development of rice
      plants and thereby contributed to lower yield. Moreover, a higher concentration
      of effluent caused heavy metal toxicity as well as reduction of growth and yield
      of rice, and in the long run a more aggravated situation may threaten human
      lives, which emphasizes the obligatory adoption of effluent treatment before its
      release to the environment, and regular monitoring by government agencies needs
      to be ensured. 

PMID- 25872733
TI  - Molecular characterization of microbial communities in bioaerosols of a coal mine
      by 454 pyrosequencing and real-time PCR.
AB  - Microbial diversity and abundance in bioaerosols of a coal mine were analyzed
      based on 454 pyrosequencing and real-time polymerase chain reaction (PCR). A
      total of 37,191 high quality sequences were obtained and could be classified into
      531, 1730 and 448 operational taxonomic units respectively for archaea, bacteria
      and fungi at 97% sequence similarity. The Shannon diversity index for archaea,
      bacteria and fungi was respectively 4.71, 6.29 and 3.86, indicating a high
      diversity in coal mine bioaerosols. Crenarchaeota, Proteobacteria and Ascomycota
      were the dominant phyla for archaea, bacteria and fungi, respectively. The
      concentrations of total archaea, bacteria and fungi were 1.44*10(8), 1.02*10(8)
      and 9.60*10(4) cells/m3, respectively. Methanotrophs observed in bioaerosols
      suggested possible methane oxidation in the coal mine. The identified potential
      pathogens to coal miners, such as Acinetobacter schindleri, Aeromonas
      cavernicola, Alternaria alternata, Aspergillus penicillioides, Cladosporium
      cladosporioides, and Penicillium brevicompactum were also observed. This was the
      first investigation of microbial diversity and abundance in coal mine
      bioaerosols. The investigation of microbial communities would be favorable in
      promoting the progress of methane control based on microbial technique and
      concern on coal miners' health.

PMID- 25872734
TI  - Risk assessment of Giardia from a full scale MBR sewage treatment plant caused by
      membrane integrity failure.
AB  - Membrane bioreactors (MBR) are highly efficient at intercepting particles and
      microbes and have become an important technology for wastewater reclamation.
      However, many pathogens can accumulate in activated sludge due to the long
      residence time usually adopted in MBR, and thus may pose health risks when
      membrane integrity problems occur. This study presents data from a survey on the
      occurrence of water-borne Giardia pathogens in reclaimed water from a full-scale
      wastewater treatment plant with MBR experiencing membrane integrity failure, and
      assessed the associated risk for green space irrigation. Due to membrane
      integrity failure, the MBR effluent turbidity varied between 0.23 and 1.90 NTU
      over a period of eight months. Though this turbidity level still met reclaimed
      water quality standards (<=5 NTU), Giardia were detected at concentrations of 0.3
      to 95 cysts/10 L, with a close correlation between effluent turbidity and Giardia
      concentration. All beta-giardin gene sequences of Giardia in the WWTP influents
      were genotyped as Assemblages A and B, both of which are known to infect humans.
      An exponential dose-response model was applied to assess the risk of infection by
      Giardia. The risk in the MBR effluent with chlorination was 9.83*10(-3), higher
      than the acceptable annual risk of 1.0*10(-4). This study suggested that membrane
      integrity is very important for keeping a low pathogen level, and multiple
      barriers are needed to ensure the biological safety of MBR effluent.

PMID- 25872735
TI  - "Sandwich Technique" via a Right Ventricle Incision to Repair Postinfarction
      Ventricular Septal Defects.
AB  - BACKGROUND: Residual shunting and mortality are problems associated with the
      current surgical repair techniques for postinfarction ventricular septal defects
      (VSD). We developed the "sandwich technique" via a right ventricle incision and
      assessed the surgical outcome of 13 years of experience with this technique.
      METHODS: Between June 2001 and March 2013, 25 consecutive patients with
      postinfarction VSD underwent surgical repair using this technique. This technique
      includes the following: Application of direct ultrasonography to the right
      ventricular (RV) wall enables the surgeon to visualize the lesion, perform an
      appropriate incision into the RV, and perform a trabecular resection. One patch
      is placed on the left ventricular (LV) side and the other on the RV side of the
      VSD. The VSD is sealed with gelatin-resorcin-formalin (GRF) glue between the two
      patches. RESULTS: Thirty-day mortality was 0% (0/25 case). A postoperative major
      shunt occurred in three patients (12%, 3/25) and two of them required reoperation
      (8%, 2/25). Hospital mortality was 28% (seven patients). Mean follow-up period
      was 4.2 +/- 3.7 years. The overall survival at one, five, and 10 years was 71 +/-
      9%, 65 +/- 10%, and 56 +/- 12%, respectively. There was no cardiac death during
      follow-up in the patients who survived for six months after the surgery. No
      tissue degeneration related to GRF glue was noted. CONCLUSION: The "sandwich
      technique" via a right ventricle incision results in a low incidence of
      postoperative leak and good short- and mid-term survival.

PMID- 25872736
TI  - Turn-on and label-free fluorescence detection of lead ions based on target
      induced G-quadruplex formation.
AB  - Using a guanine-rich sequence (AGRO100) and N-methyl mesoporphyrin IX (NMM), a
      turn-on and label-free fluorescent Pb(2+) sensor with high sensitivity and low
      background fluorescence was presented as a representative of five turn-on sensing
      systems. 

PMID- 25872737
TI  - Local strain effect on the thermal transport of graphene nanoribbons: a molecular
      dynamics investigation.
AB  - Strain engineering of the thermal conductivity of graphene is highly desirable
      for various nanoscale thermal devices. Previous investigations have been focused
      mainly on the uniform strain applied uniaxially or biaxially. In this work we
      investigated, by non-equilibrium molecular dynamics simulations, the thermal
      transport behavior of graphene nanoribbons under local, nonuniform strain. A
      capped carbon nanotube (CNT) is used as a representative tip to indent the
      graphene, which creates a local stress field similar to those induced by
      nanoindentation or molecular adsorption. The relationship among structural
      deformations, phonon transport, and stress field was analyzed, and the effects of
      indentation depth and tip-surface interaction strength were discussed. More than
      50% reduction of thermal conductance can be observed for a 20 nm * 5 nm graphene
      nanoribbon upon indentation. Our study revealed that the thermal transport of
      graphene responds flexibly and sensitively to the local strain, which can be
      exploited for new functional nanodevices across various disciplines such as
      position sensing or molecular sensing. Thermal sensors based on graphene can then
      be constructed. 

PMID- 25872738
TI  - Synthetic small molecules that induce neuronal differentiation in neuroblastoma
      and fibroblast cells.
AB  - An investigation was conducted to demonstrate that neurodazine (Nz) and
      neurodazole (Nzl), two imidazole-based small molecules, promote neuronal
      differentiation in both neuroblastoma and fibroblast cells. The results show that
      differentiated cells generated by treatment with Nz and Nzl express neuron
      specific markers. The ability of Nz and Nzl to induce neurogenesis of
      neuroblastoma and fibroblast cells was found to be comparable to those of the
      known neurogenic factors, retinoic acid and trichostatin A. In addition, the
      cells differentiated by Nz and Nzl are observed to express different isoforms of
      glutamate receptors. The results of signaling pathway studies reveal that two
      substances enhance neurogenesis in neuroblastoma cells by activating Wnt and Shh
      signaling pathways and neurogenesis in fibroblast cells by mainly activating the
      Wnt signaling pathway. Observations made in the present study suggest that Nz and
      Nzl will serve as chemical tools to generate specific populations of neuronal
      cells from readily available and simply manageable cells. 

PMID- 25872739
TI  - Chikungunya virus fusion properties elucidated by single-particle and bulk
      approaches.
AB  - Chikungunya virus (CHIKV) is a rapidly spreading, enveloped alphavirus causing
      fever, rash and debilitating polyarthritis. No specific treatment or vaccines are
      available to treat or prevent infection. For the rational design of vaccines and
      antiviral drugs, it is imperative to understand the molecular mechanisms involved
      in CHIKV infection. A critical step in the life cycle of CHIKV is fusion of the
      viral membrane with a host cell membrane. Here, we elucidate this process using
      ensemble-averaging liposome-virus fusion studies, in which the fusion behaviour
      of a large virus population is measured, and a newly developed microscopy-based
      single-particle assay, in which the fusion kinetics of an individual particle can
      be visualised. The combination of these approaches allowed us to obtain detailed
      insight into the kinetics, lipid dependency and pH dependency of hemifusion. We
      found that CHIKV fusion is strictly dependent on low pH, with a threshold of pH
      6.2 and optimal fusion efficiency below pH 5.6. At this pH, CHIKV fuses rapidly
      with target membranes, with typically half of the fusion occurring within 2 s
      after acidification. Cholesterol and sphingomyelin in the target membrane were
      found to strongly enhance the fusion process. By analysing our single-particle
      data using kinetic models, we were able to deduce that the number of rate
      limiting steps occurring before hemifusion equals about three. To explain these
      data, we propose a mechanistic model in which multiple E1 fusion trimers are
      involved in initiating the fusion process.

PMID- 25872740
TI  - Development of a Newcastle disease virus vector expressing a foreign gene through
      an internal ribosomal entry site provides direct proof for a sequential
      transcription mechanism.
AB  - In the present study, we developed a novel approach for foreign gene expression
      by Newcastle disease virus (NDV) from a second ORF through an internal ribosomal
      entry site (IRES). Six NDV LaSota strain-based recombinant viruses vectoring the
      IRES and a red fluorescence protein (RFP) gene behind the nucleocapsid (NP),
      phosphoprotein (P), matrix (M), fusion (F), haemagglutinin-neuraminidase (HN) or
      large polymerase (L) gene ORF were generated using reverse genetics technology.
      The insertion of the second ORF slightly attenuated virus pathogenicity, but did
      not affect ability of the virus to grow. Quantitative measurements of RFP
      expression in virus-infected DF-1 cells revealed that the abundance of viral
      mRNAs and red fluorescence intensity were positively correlated with the gene
      order of NDV, 3'-NP-P-M-F-HN-L-5', proving the sequential transcription mechanism
      for NDV. The results herein suggest that the level of foreign gene expression
      could be regulated by selecting the second ORF insertion site to maximize the
      efficacy of vaccine and gene therapy. 

PMID- 25872741
TI  - Hepatitis C virus NS5A protein blocks epidermal growth factor receptor
      degradation via a proline motif- dependent interaction.
AB  - Hepatitis C virus (HCV) establishes a persistent infection that in many cases
      leads to cirrhosis and hepatocellular carcinoma. The non-structural 5A protein
      (NS5A) has been implicated in this process as it contains a C-terminal
      polyproline motif (termed P2) that binds to Src homology 3 (SH3) domains to
      regulate cellular signalling and trafficking pathways. We have shown previously
      that NS5A impaired epidermal growth factor (EGF) receptor (EGFR) endocytosis,
      thereby inhibiting EGF-stimulated EGFR degradation by a mechanism that remained
      unclear. As EGFR has been implicated in HCV cell entry and trafficking of the
      receptor involves several SH3-domain containing proteins, we investigated in more
      detail the mechanisms by which NS5A perturbs EGFR trafficking. We demonstrated
      that the P2 motif was required for the NS5A-mediated disruption to EGFR
      trafficking. We further demonstrated that the P2 motif was required for an
      interaction between NS5A and CMS, a homologue of CIN85 that has previously been
      implicated in EGFR endocytosis. We provided evidence that CMS was involved in the
      NS5A-mediated perturbation of EGFR trafficking. We also showed that NS5A effected
      a loss of EGFR ubiquitination in a P2-motif-dependent fashion. These data provide
      clues to the mechanism by which NS5A regulates the trafficking of a key cellular
      receptor and demonstrate for the first time the ability of NS5A to regulate host
      cell ubiquitination pathways. 

PMID- 25872742
TI  - Subcapsular sinus macrophages limit acute gammaherpesvirus dissemination.
AB  - Lymphocyte proliferation, mobility and longevity make them prime targets for
      virus infection. Myeloid cells that process and present environmental antigens to
      lymphocytes are consequently an important line of defence. Subcapsular sinus
      macrophages (SSMs) filter the afferent lymph and communicate with B-cells. How
      they interact with B-cell-tropic viruses is unknown. We analysed their encounter
      with murid herpesvirus-4 (MuHV-4), an experimentally accessible gammaherpesvirus
      related to Kaposi's sarcoma-associated herpesvirus. MuHV-4 disseminated via lymph
      nodes, and intranasally or subcutaneously inoculated virions readily infected
      SSMs. However, this infection was poorly productive. SSM depletion with
      clodronate-loaded liposomes or with diphtheria toxin in CD169-diphtheria toxin
      receptor transgenic mice increased B-cell infection and hastened virus spread to
      the spleen. Dendritic cells provided the main route to B-cells, and SSMs slowed
      host colonization, apparently by absorbing virions non-productively from the
      afferent lymph. 

PMID- 25872743
TI  - Proteomic analysis of the occlusion-derived virus of Clostera anachoreta
      granulovirus.
AB  - To date, proteomic studies have been performed on occlusion-derived viruses
      (ODVs) from five members of the family Baculoviridae, genus Alphabaculovirus, but
      only a single member of the genus Betabaculovirus (Pieris rapae granulovirus). In
      this study, LC-MS/MS was used to analyse the ODV proteins of Clostera anachoreta
      granulovirus (ClanGV), another member of the genus Betabaculovirus. The results
      indicated that 73 proteins, including the products of 27 baculovirus core genes,
      were present in ClanGV ODVs. This is the largest number of ODV proteins
      identified in baculoviruses to date. To the best of our knowledge, 24 of these
      proteins were newly identified as ODV-associated proteins. Twelve of the proteins
      were shared by all seven of the other baculoviruses that have been analysed by
      proteomic techniques, including P49, PIF-2, ODV-EC43, P74, P6.9, P33, VP39, ODV
      EC27, VP91, GP41, VLF-1 and VP1054. ClanGV shared between 20 and 36 ODV proteins
      with each of the other six baculoviruses that have been analysed by proteomics.
      Ten proteins were identified only as ODV components of ClanGV and PrGV: Clan22,
      Clan27, Clan69, Clan83, Clan84, Clan90, Clan116, Clan94, FGF-3 and ME53, the
      first seven of which were encoded by betabaculovirus-specific genes. These
      findings may provide novel insights into baculovirus structure as well as reveal
      similarities and differences between alphabaculoviruses and betabaculoviruses.

PMID- 25872744
TI  - Viral evolution in HLA-B27-restricted CTL epitopes in human immunodeficiency
      virus type 1-infected individuals.
AB  - The HLA-B27 allele is over-represented among human immunodeficiency virus type 1
      infected long-term non-progressors. In these patients, strong CTL responses
      targeting HLA-B27-restricted viral epitopes have been associated with long-term
      asymptomatic survival. Indeed, loss of control of viraemia in HLA-B27 patients
      has been associated with CTL escape at position 264 in the immunodominant KK10
      epitope. This CTL escape mutation in the viral Gag protein has been associated
      with severe viral attenuation and may require the presence of compensatory
      mutations before emerging. Here, we studied sequence evolution within HLA-B27
      restricted CTL epitopes in the viral Gag protein during the course of infection
      of seven HLA-B27-positive patients. Longitudinal gag sequences obtained at
      different time points around the time of AIDS diagnosis were obtained and
      analysed for the presence of mutations in epitopes restricted by HLA-B27, and for
      potential compensatory mutations. Sequence variations were observed in the HLA
      B27-restricted CTL epitopes IK9 and DR11, and the immunodominant KK10 epitope.
      However, the presence of sequence variations in the HLA-B27-restricted CTL
      epitopes could not be associated with an increase in viraemia in the majority of
      the patients studied. Furthermore, we observed low genetic diversity in the gag
      region of the viral variants throughout the course of infection, which is
      indicative of low viral replication and corresponds to the low viral load
      observed in the HLA-B27-positive patients. These data indicated that control of
      viral replication can be maintained in HLA-B27-positive patients despite the
      emergence of viral mutations in HLA-B27-restricted epitopes. 

PMID- 25872745
TI  - Hepatitis B virus X protein activates the ATM-Chk2 pathway and delays cell cycle
      progression.
AB  - Genetic instability is intimately associated with tumour development. In
      particular, liver cancers associated with hepatitis B virus (HBV) exhibit high
      genetic instability; however, our understanding of the underlying molecular
      mechanisms remains limited. In this study, we found that gamma-H2AX, a marker of
      DNA double-strand breaks (DSBs), and the levels of phospho-Chk2 (p-Chk2, the
      activated form) were significantly elevated in HBV-associated hepatocellular
      carcinomas and neighbouring regenerating nodules. Likewise, introduction of the
      pHBV or pMyc-HBx plasmids into cells induced accumulation of gamma-H2AX foci and
      increased the p-Chk2 level. In these cells, inhibitory phosphorylation of Cdc25C
      phosphatase (Ser(216)) and CDK1 (Tyr(15)) was elevated; consequently, cell-cycle
      progression was delayed at G2/M phase, suggesting that activation of the ATM-Chk2
      pathway by the HBV X protein (HBx) induces cell-cycle delay. Accordingly,
      inhibition of ataxia telangiectasia mutated (ATM) by caffeine or siRNA abolished
      the increase in the p-Chk2 level and restored the delayed CDK1 kinase activity in
      ChangX cells. We also found that cytoplasmic HBx, but not nuclear HBx, induced
      reactive oxygen species (ROS) production and led to the accumulation of gamma
      H2AX foci and the increased p-Chk2 level. Together, these data indicate that HBx
      induced ROS accumulation induces DNA damage that activates the ATM-Chk2 pathway.
      Our findings provide insight into the mechanisms of HBV pathogenesis.

PMID- 25872748
TI  - Mix and print: fast optimization of mesoporous CuCeZrO(w) for catalytic oxidation
      of n-hexane.
AB  - Fast optimization of mesoporous ternary metal oxide (CuCeZrO(w)) catalysts for n
      hexane oxidation is achieved via a newly developed combinatorial approach based
      on ink-jet printing assisted synthesis and multi-dimensional group testing.

PMID- 25872747
TI  - Assessing site performance in the Altair study, a multinational clinical trial.
AB  - BACKGROUND: Reviewing clinical trial site performance identifies strategies to
      control outcomes. Performance across 5 geographical regions (36 sites across
      Asia, Australia, Europe, North America and Latin America) was investigated in a
      study that randomised 322 HIV-infected individuals. METHODS: Regional performance
      was compared using descriptive analysis for time to site opening, recruitment,
      quality of data and laboratory samples. Follow-up consisted of 10 visits (96
      weeks), electronic data collection (EDC) within 7 days of a visit and serious
      adverse events (SAEs) reported within 24 hours of site awareness. RESULTS: Median
      days to site opening was 250 (188 to 266), ranging from 177 (158 to 200)
      (Australia) to 265 (205 to 270) (Europe). Median days to ethics and regulatory
      approval was 182 (120 to 241) and 218 (182 to 341) days, respectively. Within
      regions, time to approval ranged from 187 (91 to 205) days (Australia) to 276
      (175 to 384) days (Europe). Time to first randomisation ranged from 282 (250 to
      313) days (Australia) to 426 (420 to 433) days (North America). Recruitment was
      lower than forecasted in Asia, Australia, Europe and North America at 89%, 77%,
      91% and 43%, respectively. The converse was true in Latin America where despite
      ethics, regulatory and contractual delays, recruitment was 104% of predicted.
      Median days to EDC was 7 (3 to 16), ranging from 3 (1 to 16) (Asia) to 13 (8 to
      14) days (North America). Median days for initial SAE submission to sponsor was 6
      (2 to 20), ranging from 4 (2 to 18) (Latin America) to 24 (5 to 46) days
      (Australia). Sites took longer to submit final reports, overall median of 28 (7
      to 91) days, ranging from 7 days (Australia) to 67 (23 to 103) days (Europe).
      CONCLUSIONS: Population availability and time to ethics and regulatory approvals
      influence recruitment; therefore accurate feasibility assessments are critical to
      site selection. Time to ethics and regulatory approval may not limit site
      inclusion if compensated by rapid recruitment. Identifying potential delays and
      methods for reduction can decrease time and costs for sponsors. TRIAL
      REGISTRATION: Clinical Trials.Gov identifier: NCT00335322. Date of registration:
      8 June 2006.

PMID- 25872749
TI  - Ranolazine for the treatment of atrial fibrillation.
AB  - INTRODUCTION: Atrial fibrillation (AF) is a frequent occurrence with advancing
      age and is associated with increased morbidity and mortality. Unfortunately, the
      currently available AF therapies have a great deal of side effects. AREAS
      COVERED: In this review, the authors discuss the evidence upon which the use of
      Ranolazine as an anti-arrhythmic drug is based. Specifically, the authors review
      the Phase I-III trials that studied ranolazine as potential treatment for AF.
      They also discuss the efficacy, safety, tolerability and side effects and compare
      the MERLIN TIMI 36, HARMONY and ROLE trials. EXPERT OPINION: Although ranolazine
      is considered an anti-angina drug, it may also be, according to the available
      data, used in patients with AF. Ranolazine has anti-AF efficacy, both alone or in
      combination with other drugs such as amiodarone and dronedarone. Indeed, its
      efficacy has been demonstrated in various settings such as the termination of
      paroxysmal AF, the facilitation of AF electrical cardioversion, and postoperative
      AF prevention. Although there is a great deal of evidence from pioneering
      experimental studies, the clinical evidence of the AF-suppressing effect of
      ranolazine is derived from studies with small sample size or from secondary
      analyses. A better understanding of the role of ranolazine as an anti-AF drug
      will be obtained through larger, prospective, placebo-controlled clinical trials
      in different populations.

PMID- 25872750
TI  - Capillary electrophoresis with electrochemiluminescence detection for the
      simultaneous determination of cisatracurium besylate and its degradation products
      in pharmaceutical preparations.
AB  - Capillary electrophoresis with electrochemiluminescence detection for the
      simultaneous analysis of cisatracurium besylate and its degradation products
      (laudanosine, quaternary monoacrylate) in pharmaceutical preparation was
      developed and fully validated. The significant parameters that influence
      capillary electrophoresis separation and electrochemiluminescence detection were
      optimized. The total analysis time of the analytes was 15 min. The linearities of
      the method were 0.1~40.0 MUg/mL for cisatracurium besylate and 0.04~8.00 MUg/mL
      for laudanosine, with correlation coefficients (r) of 0.999 and 0.998,
      respectively. The detection limits (S/N = 3) were 83.0 ng/mL for cisatracurium
      besylate and 32.0 ng/mL for laudanosine. The intraday relative standard
      deviations of the analytes were <3.0%, and the interday relative standard
      deviations were <8.0%. The developed method was cost-effective, sensitive, fast,
      and resource-saving, which was suitable for the ingredient analysis in
      pharmaceutical preparation. 

PMID- 25872751
TI  - Leveraging prognostic baseline variables to gain precision in randomized trials.
AB  - We focus on estimating the average treatment effect in a randomized trial. If
      baseline variables are correlated with the outcome, then appropriately adjusting
      for these variables can improve precision. An example is the analysis of
      covariance (ANCOVA) estimator, which applies when the outcome is continuous, the
      quantity of interest is the difference in mean outcomes comparing treatment
      versus control, and a linear model with only main effects is used. ANCOVA is
      guaranteed to be at least as precise as the standard unadjusted estimator,
      asymptotically, under no parametric model assumptions and also is locally
      semiparametric efficient. Recently, several estimators have been developed that
      extend these desirable properties to more general settings that allow any real
      valued outcome (e.g., binary or count), contrasts other than the difference in
      mean outcomes (such as the relative risk), and estimators based on a large class
      of generalized linear models (including logistic regression). To the best of our
      knowledge, we give the first simulation study in the context of randomized trials
      that compares these estimators. Furthermore, our simulations are not based on
      parametric models; instead, our simulations are based on resampling data from
      completed randomized trials in stroke and HIV in order to assess estimator
      performance in realistic scenarios. We provide practical guidance on when these
      estimators are likely to provide substantial precision gains and describe a quick
      assessment method that allows clinical investigators to determine whether these
      estimators could be useful in their specific trial contexts.

PMID- 25872753
TI  - Accuracy of EUS and CT imaging in preoperative gastric cancer staging.
AB  - BACKGROUND: Neoadjuvant therapy is recommended for locally advanced gastric
      cancer patients (stage IB-IIIC). The objective of this study is to evaluate the
      accuracy of endoscopic ultrasound (EUS) and computed tomography (CT) in
      identifying patients with locally advanced gastric cancer. METHODS: Patients with
      gastric adenocarcinoma who underwent gastrectomy at our institution were
      reviewed. Preoperative EUS and CT staging were compared with pathologic staging
      to determine accuracy. RESULTS: Between 2001 and 2013, 280 patients were
      identified. Forty-nine patients (18%) who underwent preoperative staging by EUS
      were analyzed. The accuracy of EUS in identifying individual T stage and N stage
      was 41.0% and 42.9%, respectively. EUS had moderate accuracy in differentiating
      locally advanced from early (stage 0-IA) disease (75.5%, area under curve (AUC)
      0.772). For individual T stage and N stage, the accuracy of CT was 4.0% and 56%,
      respectively. CT had relatively poor accuracy in differentiating locally advanced
      from early disease (60.0%, AUC 0.649). CONCLUSIONS: EUS and CT had poor
      performance in identifying individual T and N stage although EUS demonstrated
      moderate accuracy in identifying patients with locally advanced disease. A
      combined staging approach, in addition to further optimization of staging
      modalities, is required for accurate staging for patients with gastric cancer.

PMID- 25872752
TI  - Epidemiology of meningiomas post-Public Law 107-206: The Benign Brain Tumor
      Cancer Registries Amendment Act.
AB  - BACKGROUND: The current analysis follows the implementation of Public Law 107
      260, the Benign Brain Tumor Cancer Registries Amendment Act, which mandated the
      collection of nonmalignant brain tumors. METHODS: Meningiomas were selected from
      the Surveillance, Epidemiology, and End Results (SEER) Program database for the
      years 2004 to 2011. Demographic and clinical characteristics, initial treatment
      patterns, and survival outcomes were evaluated using surveillance epidemiology
      statistical methods. RESULTS: The average annual age-adjusted incidence rate per
      100,000 population was 7.62 (95 % confidence interval [CI], 7.55-7.68) for all
      meningiomas, 7.18 (95% CI, 7.12-7.25) for benign meningiomas, 0.32 (95% CI, 0.31
      0.33) for borderline malignant meningiomas, and 0.12 (95% CI, 0.11-0.12) for
      malignant meningiomas. The annual rates increased for benign and borderline
      malignant tumors but decreased for malignant tumors. The rates for women exceeded
      those for men, especially for those with benign meningiomas. Black race was
      associated with significantly higher rates as was advancing age. Greater than 80%
      of tumors were located in cerebral meninges. Diagnostic confirmation through
      pathology occurred for approximately 50% of benign tumors, 90% of borderline
      malignant tumors, and 80% of malignant tumors. No initial treatment was reported
      for greater than 60% of benign tumors, 29% of borderline malignant tumors, or 31%
      of malignant tumors. The 5-year relative survival estimates for benign tumors,
      borderline malignant tumors, and malignant tumors were 85.6% (95% confidence
      interval [CI], 85%-86.2%), 82.3% (95% CI, 79.3%-84.8%), and 66% (95% CI, 60.6%
      70.9%), respectively. Predictors of poorer survival were advanced age, being male
      gender, black race, no initial treatment, and malignant tumor behavior.
      CONCLUSIONS: The current analysis demonstrates that there is an increasing
      incidence of nonmalignant meningiomas, probably because of reporting learning
      curves associated with the implementation of Public Law 107-260. The high
      proportion of cases who receive no initial treatment is a survival outcome
      concern, especially for patients with malignant meningiomas.

PMID- 25872754
TI  - Identifying Factors Associated With Dropout During Prerandomization Run-in Period
      From an mHealth Physical Activity Education Study: The mPED Trial.
AB  - BACKGROUND: The mobile phone-based physical activity education (mPED) trial is a
      randomized controlled trial (RCT) evaluating a mobile phone-delivered physical
      activity intervention for women. The study includes a run-in period to maximize
      the internal validity of the intervention trial, but little is known about
      factors related to successful run-in completion, and thus about potential threats
      to external validity. OBJECTIVE: Objectives of this study are (1) to determine
      the timing of dropout during the run-in period, reasons for dropout, optimum run
      in duration, and relevant run-in components, and (2) to identify predictors of
      failure to complete the run-in period. METHODS: A total of 318 physically
      inactive women met preliminary eligibility criteria and were enrolled in the
      study between May 2011 and April 2014. A 3-week run-in period was required prior
      to randomization and included using a mobile phone app and wearing a pedometer.
      Cross-sectional analysis identified predictors of dropout. RESULTS: Out of 318
      participants, 108 (34.0%) dropped out prior to randomization, with poor adherence
      using the study equipment being the most common reason. Median failure time was
      17 days into the run-in period. In univariate analyses, nonrandomized
      participants were younger, had lower income, were less likely to drive regularly,
      were less likely to have used a pedometer prior to the study, were generally less
      healthy, had less self-efficacy for physical activity, and reported more
      depressive symptoms than randomized participants. In multivariate competing risks
      models, not driving regularly in the past month and not having used a pedometer
      prior to the study were significantly associated with failure to be randomized
      (P=.04 and .006, respectively), controlling for age, race/ethnicity, education,
      shift work, and use of a study-provided mobile phone. CONCLUSIONS: Regular
      driving and past pedometer use were associated with reduced dropout during the
      prerandomization run-in period. Understanding these characteristics is important
      for identifying higher-risk participants, and implementing additional help
      strategies may be useful for reducing dropout. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT01280812; https://clinicaltrials.gov/ct2/show/NCT01280812
      (Archived by WebCite at http://www.webcitation.org/6XFC5wvrP).

PMID- 25872755
TI  - Retrospective correction of involuntary microscopic head movement using highly
      accelerated fat image navigators (3D FatNavs) at 7T.
AB  - PURPOSE: The goal of the present study was to use a three-dimensional (3D)
      gradient echo volume in combination with a fat-selective excitation as a 3D
      motion navigator (3D FatNav) for retrospective correction of microscopic head
      motion during high-resolution 3D structural scans of extended duration. The fat
      excitation leads to a 3D image that is itself sparse, allowing high parallel
      imaging acceleration factors--with the additional advantage of a minimal
      disturbance of the water signal used for the host sequence. METHODS: A 3D FatNav
      was inserted into two structural protocols: an inversion-prepared gradient echo
      at 0.33 * 0.33 * 1.00 mm resolution and a turbo spin echo at 600 MUm isotropic
      resolution. RESULTS: Motion estimation was possible with high precision, allowing
      retrospective motion correction to yield clear improvements in image quality,
      especially in the conspicuity of very small blood vessels. CONCLUSION: The highly
      accelerated 3D FatNav allowed motion correction with noticeable improvements in
      image quality, even for head motion which was small compared with the voxel
      dimensions of the host sequence.

PMID- 25872756
TI  - Beta oscillations reflect memory and motor aspects of spoken word production.
AB  - Two major components form the basis of spoken word production: the access of
      conceptual and lexical/phonological information in long-term memory, and motor
      preparation and execution of an articulatory program. Whereas the motor aspects
      of word production have been well characterized as reflected in alpha-beta
      desynchronization, the memory aspects have remained poorly understood. Using
      magnetoencephalography, we investigated the neurophysiological signature of not
      only motor but also memory aspects of spoken-word production. Participants named
      or judged pictures after reading sentences. To probe the involvement of the
      memory component, we manipulated sentence context. Sentence contexts were either
      constraining or nonconstraining toward the final word, presented as a picture. In
      the judgment task, participants indicated with a left-hand button press whether
      the picture was expected given the sentence. In the naming task, they named the
      picture. Naming and judgment were faster with constraining than nonconstraining
      contexts. Alpha-beta desynchronization was found for constraining relative to
      nonconstraining contexts pre-picture presentation. For the judgment task, beta
      desynchronization was observed in left posterior brain areas associated with
      conceptual processing and in right motor cortex. For the naming task, in addition
      to the same left posterior brain areas, beta desynchronization was found in left
      anterior and posterior temporal cortex (associated with memory aspects), left
      inferior frontal cortex, and bilateral ventral premotor cortex (associated with
      motor aspects). These results suggest that memory and motor components of spoken
      word production are reflected in overlapping brain oscillations in the beta band.

PMID- 25872757
TI  - A critical view on catalytic pyrolysis of biomass.
AB  - The rapid heating of biomass in an oxygen-free environment optimizes the yield of
      fast-pyrolysis liquids. This liquid comprises a mix of acids, (dehydrated)
      carbohydrates, aldehydes, ketones, lignin fragments, aromatics, and alcohols,
      limiting its use. Deoxygenation of these liquids to replace hydrocarbons
      represents significant challenges. Catalytic pyrolysis is seen as a promising
      route to yield liquids with a higher quality. In this paper, literature data on
      catalytic fast pyrolysis of biomass are reviewed and deoxygenation results
      correlated with the overall carbon yield. Evidence is given that in an initial
      stage of the catalytic process reactive components are converted to coke, gas,
      and water, and only to a limited extent to a liquid product. Catalysts are not
      yet good enough, and an appropriate combination of pyrolysis conditions, reactive
      products formed, and different reactions to take place to yield improved quality
      liquids may be practically impossible. 

PMID- 25872758
TI  - Efficient Photocatalytic H2 Evolution: Controlled Dewetting-Dealloying to
      Fabricate Site-Selective High-Activity Nanoporous Au Particles on Highly Ordered
      TiO2 Nanotube Arrays.
AB  - Anodic self-organized TiO2 nanostumps are formed and exploited for self-ordering
      dewetting of Au-Ag sputtered films. This forms ordered particle configurations at
      the tube top (crown position) or bottom (ground position). By dealloying from a
      minimal amount of noble metal, porous Au nanoparticles are then formed, which,
      when in the crown position, allow for a drastically improved photocatalytic H2
      production compared with nanoparticles produced by conventional dewetting
      processes. 

PMID- 25872759
TI  - Collateral damage to the ureter and Nitinol stone baskets during thulium fiber
      laser lithotripsy.
AB  - BACKGROUND: The experimental Thulium fiber laser (TFL) is currently being studied
      as a potential alternative lithotripter to the clinical gold standard Holmium:YAG
      laser. Safety studies characterizing undesirable Holmium:YAG laser-induced damage
      to ureter tissue and stone baskets have been previously reported. Similarly, this
      study characterizes TFL induced ureter and stone basket damage. METHODS: A TFL
      beam with energy of 35 mJ per pulse, pulse duration of 500 us, and variable pulse
      rates of 50-500 Hz, was delivered through 100-um-core optical fibers, to either
      porcine ureter wall, in vitro, or a standard 1.9-Fr Nitinol stone basket wire.
      Ureter perforation times were measured and gross, histological, and optical
      coherence tomography images of the ablation area were acquired. Stone basket
      damage was graded as a function of pulse rate, number of pulses, and working
      distance. RESULTS: TFL operation at 150, 300, and 500 Hz produced mean ureter
      perforation times of 7.9, 3.8, and 1.8 seconds, respectively. Collateral damage
      widths averaged 510, 370, and 310 um. Nitinol wire damage decreased with working
      distance and was non-existent at distances greater than 1.0 mm. In contact mode,
      500 pulses delivered at pulse rates >=300 Hz (<=1.5 seconds) were sufficient to
      cut Nitinol wires. CONCLUSIONS: The TFL, operated in low pulse energy and high
      pulse rate mode, may provide a greater safety margin than the standard
      Holmium:YAG laser for lithotripsy, as evidenced by longer TFL ureter perforation
      times and shorter non-contact working distances for stone basket damage than
      previously reported with Holmium:YAG laser.

PMID- 25872760
TI  - The granule porosity controls the loss of compactibility for both dry- and wet
      processed cellulose granules but at different rate.
AB  - The aim of this study was to investigate the role of porosity on the compression
      behavior and tablet tensile strength for granules produced by a dry granulation
      procedure. Microcrystalline cellulose was used as a typical pharmaceutical
      excipient and a comparison was made with the effect of granule porosity on the
      compression behavior and tablet tensile strength of wet-processed granules of the
      same composition. Both the wet and dry granulation process caused a loss in
      compactibility of the material that was controlled by the granule porosity up to
      a critical point of porosity and friability. Above this threshold value of
      porosity, the granules nearly collapsed completely into primary particles during
      compression. In these cases, the micro-structure and tensile strength of the
      formed tablets resembled that of tablets formed from the original ungranulated
      powder.

PMID- 25872761
TI  - Theoretical Studies of the Reactions CFx H3-x COOR+Cl and CF3 COOCH3 +OH.
AB  - The mechanism and kinetics of the reactions of CF(3)COOCH(2)CH(3),
      CF(2)HCOOCH(3), and CF(3)COOCH(3) with Cl and OH radicals are studied using the
      B3LYP, MP2, BHandHLYP, and M06-2X methods with the 6-311G(d,p) basis set. The
      study is further refined by using the CCSD(T) and QCISD(T)/6-311++G(d,p) methods.
      Seven hydrogen-abstraction channels are found. All the rate constants, computed
      by a dual-level direct method with a small-curvature tunneling correction, are in
      good agreement with the experimental data. The tunneling effect is found to be
      important for the calculated rate constants in the low-temperature range. For the
      reaction of CF(3)COOCH(2)CH(3) +Cl, H-abstraction from the CH(2) group is found
      to be the dominant reaction channel. The standard enthalpies of formation for the
      species are also calculated. The Arrhenius expressions are fitted within 200-1000
      K as kT(1) =8.4*10(-20) T (2.63) exp(381.28/T), kT(2) =2.95*10(-21) T (3.13) exp(
      103.21/T), kT(3) =1.25*10(-23) T (3.37) exp(791.98/T), and kT(4) =4.53*10(-22) T
      (3.07) exp(465.00/T).

PMID- 25872762
TI  - The significance of the co-existence of osteopontin and tumor-associated
      macrophages in gastric cancer progression.
AB  - BACKGROUND: Osteopontin (OPN) can recruit macrophages to the site of inflammation
      and promote tumorigenesis. M2 tumor-associated macrophages (M2-TAMs) also play an
      important role in cancer progression. This study aimed to clarify the role of OPN
      and M2-TAMs co-existence in gastric cancer. METHODS: The levels of OPN and M2
      TAMs were evaluated by immunohistochemical staining in 170 resected gastric
      cancer specimens that were collected from 1998 to 2012. M2-TAMs were identified
      by staining for an M2 marker, CD204. The prognostic significance and correlation
      between OPN and CD204 expression were analyzed. A co-culture system of OPN+-AGS
      and U937 cells was designed to study the effect of OPN on the skewing of
      macrophages toward M2-TAMs for gastric cancer progression in vitro and in vivo.
      RESULTS: Patients with high expression (>50%) of OPN or CD204 exhibited poor 5
      year overall survival rates (48.61%, p = 0.0055, and 52.14%, p = 0.0498,
      respectively). A positive correlation was observed between OPN and CD204
      expression and high co-expression of OPN and CD204 demonstrated poor 5-year
      overall survival rates (48.90%, p = 0.0131). In the co-culture study, OPN was
      able to attract U937 cells and skew them toward M2-TAMs through paracrine action.
      The M2-TAMs could increase the invasiveness of OPN+-AGS cells and the growth rate
      of xenograft of a mixture of co-cultured OPN+-AGS and U937 cells. CONCLUSION: OPN
      can skew macrophages toward M2-TAMs during gastric cancer progression. The co
      existence of OPN and infiltrating M2-TAMs correlates with disease progression and
      poor survival and thus can serve as a prognostic marker in gastric cancer.

PMID- 25872763
TI  - Prevalence of impaired memory in hospitalized adults and associations with in
      hospital sleep loss.
AB  - BACKGROUND: Effective inpatient teaching requires intact patient memory, but
      studies suggest hospitalized adults may have memory deficits. Sleep loss among
      inpatients could contribute to memory impairment. OBJECTIVE: To assess memory in
      older hospitalized adults, and to test the association between sleep quantity,
      sleep quality, and memory, in order to identify a possible contributor to memory
      deficits in these patients. DESIGN: Prospective cohort study. SETTING: General
      medicine and hematology/oncology inpatient wards. PATIENTS: Fifty-nine
      hospitalized adults at least 50 years of age with no diagnosed sleep disorder.
      MEASUREMENTS: Immediate memory and memory after a 24-hour delay were assessed
      using a word recall and word recognition task from the University of Southern
      California Repeatable Episodic Memory Test. A vignette-based memory task was
      piloted as an alternative test more closely resembling discharge instructions.
      Sleep duration and efficiency overnight in the hospital were measured using
      actigraphy. RESULTS: Mean immediate recall was 3.8 words out of 15 (standard
      deviation = 2.1). Forty-nine percent of subjects had poor memory, defined as
      immediate recall score of 3 or lower. Median immediate recognition was 11 words
      out of 15 (interquartile range [IQR] = 9-13). Median delayed recall score was 1
      word, and median delayed recognition was 10 words (IQR = 8-12). In-hospital sleep
      duration and efficiency were not significantly associated with memory. The
      medical vignette score was correlated with immediate recall (r = 0.49, P < 0.01).
      CONCLUSIONS: About half of the inpatients studied had poor memory while in the
      hospital, signaling that hospitalization might not be an ideal teachable moment.
      In-hospital sleep was not associated with memory scores.

PMID- 25872764
TI  - A study of the mechanism of fluoride adsorption from aqueous solutions onto Fe
      impregnated chitosan.
AB  - The adsorption of fluoride from aqueous solutions onto an Fe-impregnated chitosan
      (Fe-CTS) granular adsorbent was studied, and the adsorption capacity was
      determined to be 1.9736 mg g(-1) at an initial fluoride concentration of 10 mg L(
      1). The effects of the initial fluoride concentration, dosage, and temperature
      were investigated using factorial design and analysis. The results indicated that
      high initial fluoride concentrations, low dosages, and low temperatures could
      enhance the fluoride adsorption capacity. In addition, Fe-CTS exhibited high
      selectivity for fluoride removal in the presence of high levels of several
      coexisting anions (nitrate, chloride, bicarbonate, and phosphate), except
      carbonate and sulfate. The adsorption process followed the Langmuir model at low
      fluoride concentrations and the Freundlich model at high initial fluoride
      concentrations. The data also fit the pseudo-second-order model. Scanning
      electron microscopy (SEM), Fourier-transform infrared (FTIR) spectroscopy, and
      extended X-ray absorption fine-structure (EXAFS) spectroscopy were used to
      elucidate the adsorption mechanism. The FTIR and EXAFS analyses revealed that Fe
      was chelated with -NH2 and -OH groups on the CTS, and fluoride adsorption on the
      Fe-CTS occurred due to ion exchange between chloride and fluoride. HIGHLIGHTS: a
      granular Fe-impregnated chitosan (Fe-CTS) adsorbent was synthesized via chelation
      of Fe ions to -OH and -NH2 groups of CTS. The Fe-CTS granular adsorbent exhibited
      high performance for the adsorption of fluoride. The mechanism of fluoride
      adsorption on Fe-CTS was elucidated using EXAFS and FTIR analyses. Fluoride
      adsorption on Fe-CTS occurred via ion exchange between chloride and fluoride.

PMID- 25872766
TI  - Objections to the use of cost-effectiveness analysis in the US: reflecting on
      'Has the time come for cost-effectiveness analysis in US health care?'.

PMID- 25872765
TI  - PARP-1 promotes autophagy via the AMPK/mTOR pathway in CNE-2 human nasopharyngeal
      carcinoma cells following ionizing radiation, while inhibition of autophagy
      contributes to the radiation sensitization of CNE-2 cells.
AB  - It was previously reported that poly-(adenosine diphosphate-ribose) polymerase-1
      (PARP-1) regulated ionizing radiation (IR)-induced autophagy in CNE-2 human
      nasopharyngeal carcinoma cells. The present study aimed to investigate whether
      PARP-1-mediated IR-induced autophagy occurred via activation of the liver kinase
      B1 (LKB1)/adenosine monophosphate-activated protein kinase (AMPK)/mammalian
      target of rapamycin (mTOR) signaling pathway in CNE-2 cells. In addition, the
      effect of PARP-1 and AMPK inhibition on the radiation sensitization of CNE-2
      cells was investigated. CNE-2 cells were treated with 10 Gy IR in the presence or
      absence of the AMPK activator 5-amino-1-beta-D-ribofuranosyl-1H-imid-azole-4
      carboxamide (AICAR). In addition, IR-treated CNE-2 cells were transfected with
      lentivirus-delivered small-hairpin RNA or treated with the AMPK inhibitor
      Compound C. Western blot analysis was used to assess the protein expression of
      PARP-1, phosphorylated (p)-AMPK, microtubule-associated protein 1 light chain 3
      (LC3)-II and p-P70S6K. Cell viability and clone formation assays were performed
      to determine the effect of PARP-1 silencing and AMPK inhibition on the radiation
      sensitization of CNE-2 cells. The results showed that IR promoted PARP-1, p-AMPK
      and LC3-II protein expression as well as decreased p-P70S6K expression compared
      with that of the untreated cells. In addition, AICAR increased the expression of
      p-AMPK and LC3-II as well as decreased p-P70S6K expression compared with that of
      the IR-only group; however, AICAR did not increase PARP-1 expression.
      Furthermore, PARP-1 gene silencing decreased the expression of PARP-1, p-AMPK and
      LC3-II as well as increased p-P70S6K expression. Compound C decreased p-AMPK and
      LC3-II expression as well as increased p-P70S6K expression; however, Compound C
      did not increase PARP-1 expression. Western blot analysis detected limited
      expression of p-LKB1 in all treatment groups. Cell viability and clone formation
      assays revealed that PARP-1 or AMPK inhibition reduced the proliferation of CNE-2
      cells following IR. In conclusion, the present study demonstrated that PARP-1
      promoted autophagy via the AMPK/mTOR pathway; in addition, PARP-1 or AMPK
      inhibition contributed to the radiation sensitization of CNE-2 cells following
      IR. However, it remains to be elucidated whether PARP-1 is an upstream mediator
      of the LKB1 pathway in CNE-2 cells following IR.

PMID- 25872767
TI  - Serum and synovial fluid nesfatin-1 concentration is associated with radiographic
      severity of knee osteoarthritis.
AB  - BACKGROUND: Nesfatin-1, a member of the adipokine family, has been detected in
      synovial fluid (SF) from OA patients. This study aimed to determine whether there
      is a marked correlation of nesfatin-1 levels in serum and SF of knee OA patients
      with the disease severity of OA. MATERIAL AND METHODS: This cross-sectional
      research enrolled 202 knee OA subjects. The Kellgren-Lawrence grading system was
      utilized to evaluate the severity of knee OA. RESULTS: Elevated nesfatin-1
      concentrations in serum were found in knee OA patients compared with the
      controls. Nesfatin-1 concentrations were markedly elevated with increased KL
      grades. Serum and SF nesfatin-1 concentrations were both significantly associated
      with the disease severity evaluated by KL grading criteria. CONCLUSIONS: Our
      investigation indicates a marked association of serum and SF nesfatin-1
      concentrations with OA disease severity.

PMID- 25872770
TI  - Photooxidizing chromium catalysts for promoting radical cation cycloadditions.
AB  - The photooxidizing capabilities of selected Cr(III) complexes for promoting
      radical cation cycloadditions are described. These complexes have sufficiently
      long-lived excited states to oxidize electron-rich alkenes, thereby initiating
      [4+2] processes. These metal species augment the spectrum of catalysts explored
      in photoredox systems, as they feature unique properties that can result in
      differential reactivity from the more commonly employed ruthenium or iridium
      catalysts. 

PMID- 25872769
TI  - Experimentally manipulated sleep duration in adolescents with asthma: Feasibility
      and preliminary findings.
AB  - OBJECTIVE: To examine the impact of sleep duration on lung function and asthma
      symptoms in adolescents. METHODS: Ten adolescents with asthma (60% female, 60%
      Caucasian, mean age = 13.7 years, range 12-17) completed a 3-week randomized,
      cross-over sleep manipulation protocol. Following a week of self-selected sleep
      duration, adolescents were randomized to a five-night deficient sleep opportunity
      (6.5 hr in bed) or a healthy sleep opportunity (10 hr in bed) obtained by
      systematically changing bedtimes. Wake time remained consistent across all 3
      weeks (including weekends). Daily reports of sleep patterns and asthma symptoms,
      actigraphy, and daily peak expiratory flow rates (PEFR), as well as weekly
      spirometry and exhaled nitric oxide were collected. RESULTS: Participants
      averaged 3.2 hr less sleep (P < 0.001) per night in the short sleep condition
      versus the long sleep condition. Further, they had an 8.4% decrease overnight in
      PEFR (P = 0.007), and reported more asthma symptoms interfering with activities
      in the past 24 hr (P = 0.02) in the short sleep condition than the long sleep
      condition. No significant differences between experimental weeks were found for
      weekly spirometry or exhaled nitric oxide. CONCLUSIONS: This pilot study
      demonstrated the feasibility of a cross-over sleep manipulation protocol in
      adolescents with asthma. Since overnight decrease in PEFR is a marker of
      nocturnal asthma, and has been associated with the severity of daytime airflow
      limitation, these early-stage results suggest that shortened sleep duration may
      exacerbate adolescent asthma and associated functional impairments.

PMID- 25872771
TI  - Ryanodine receptors are targeted by anti-apoptotic Bcl-XL involving its BH4
      domain and Lys87 from its BH3 domain.
AB  - Anti-apoptotic B-cell lymphoma 2 (Bcl-2) family members target several
      intracellular Ca(2+)-transport systems. Bcl-2, via its N-terminal Bcl-2 homology
      (BH) 4 domain, inhibits both inositol 1,4,5-trisphosphate receptors (IP3Rs) and
      ryanodine receptors (RyRs), while Bcl-XL, likely independently of its BH4 domain,
      sensitizes IP3Rs. It remains elusive whether Bcl-XL can also target and modulate
      RyRs. Here, Bcl-XL co-immunoprecipitated with RyR3 expressed in HEK293 cells.
      Mammalian protein-protein interaction trap (MAPPIT) and surface plasmon resonance
      (SPR) showed that Bcl-XL bound to the central domain of RyR3 via its BH4 domain,
      although to a lesser extent compared to the BH4 domain of Bcl-2. Consistent with
      the ability of the BH4 domain of Bcl-XL to bind to RyRs, loading the BH4-Bcl-XL
      peptide into RyR3-overexpressing HEK293 cells or in rat hippocampal neurons
      suppressed RyR-mediated Ca(2+) release. In silico superposition of the 3D
      structures of Bcl-2 and Bcl-XL indicated that Lys87 of the BH3 domain of Bcl-XL
      could be important for interacting with RyRs. In contrast to Bcl-XL, the Bcl
      XL(K87D) mutant displayed lower binding affinity for RyR3 and a reduced
      inhibition of RyR-mediated Ca(2+) release. These data suggest that Bcl-XL binds
      to RyR channels via its BH4 domain, but also its BH3 domain, more specific Lys87,
      contributes to the interaction. 

PMID- 25872772
TI  - Comparison of the predictive abilities of pharmacogenetics-based warfarin dosing
      algorithms using seven mathematical models in Chinese patients.
AB  - AIM: This study is aimed to find the best predictive model for warfarin stable
      dosage. MATERIALS & METHODS: Seven models, namely multiple linear regression
      (MLR), artificial neural network, regression tree, boosted regression tree,
      support vector regression, multivariate adaptive regression spines and random
      forest regression, as well as the genetic and clinical data of two Chinese
      samples were employed. RESULTS: The average predicted achievement ratio and mean
      absolute error of the algorithms were ranging from 52.31 to 58.08% and 4.25 to
      4.84 mg/week in validation samples, respectively. The algorithm based on MLR
      showed the highest predicted achievement ratio and the lowest mean absolute
      error. CONCLUSION: At present, MLR may be still the best model for warfarin
      stable dosage prediction in Chinese population. Original submitted 10 November
      2014; Revision submitted 18 February 2015.

PMID- 25872775
TI  - Even Superdoc can't fix patients' homes.

PMID- 25872773
TI  - Online parent-targeted cognitive-behavioural therapy intervention to improve
      quality of life in families of young cancer survivors: study protocol for a
      randomised controlled trial.
AB  - BACKGROUND: Due to advances in multimodal therapies, most children survive
      cancer. In addition to the stresses of diagnosis and treatment, many families are
      now navigating the challenges of survivorship. Without sufficient support, the
      ongoing distress that parents experience after their child's cancer treatment can
      negatively impact the quality of life and psychological wellbeing of all family
      members. METHODS/DESIGN: The 'Cascade' (Cope, Adapt, Survive: Life after C AncEr)
      study is a three-arm randomised controlled trial to evaluate the feasibility and
      efficacy of a new intervention to improve the quality of life of parents of young
      cancer survivors. Cascade will be compared to a peer-support group control and a
      6-month waitlist control. Parents (n = 120) whose child (under 16 years of age)
      has completed cancer treatment in the past 1 to 12 months will be recruited from
      hospitals across Australia. Those randomised to receive Cascade will participate
      in four, weekly, 90-minute online group sessions led live by a psychologist.
      Cascade involves peer discussion on cognitive-behavioural coping skills,
      including behavioural activation, thought challenging, mindfulness and
      acceptance, communication and assertiveness skills training, problem-solving and
      goal-setting. Participants randomised to peer support will receive four, weekly,
      90-minute, live, sessions of non-directive peer support. Participants will
      complete measures at baseline, directly post-intervention, one month post
      intervention, and 6 months post-intervention. The primary outcome will be
      parents' quality of life. Secondary outcomes include parent depression, anxiety,
      parenting self-agency, and the quality of life of children in the family. The
      child cancer survivor and all siblings aged 7 to 15 years will be invited to
      complete self-report quality of life measures covering physical, emotional,
      social and school-related domains. DISCUSSION: This article reviews the empirical
      rationale for group-based, online cognitive-behavioural therapy in parents of
      children who have recently finished cancer treatment. The potential challenges of
      delivering skills-based programs online are highlighted. Cascade's
      videoconferencing technology has the potential to address the geographic and
      psychological isolation of families after cancer treatment. Teaching parents
      coping skills as they resume their normal lives after their child's cancer may
      see long-term benefits for the quality of life of the family as a whole. TRIAL
      REGISTRATION: ACTRN12613000270718 (registered 6 March 2013).

PMID- 25872774
TI  - Expression of Ca2+-permeable two-pore channels rescues NAADP signalling in TPC
      deficient cells.
AB  - The second messenger NAADP triggers Ca(2+) release from endo-lysosomes. Although
      two-pore channels (TPCs) have been proposed to be regulated by NAADP, recent
      studies have challenged this. By generating the first mouse line with
      demonstrable absence of both Tpcn1 and Tpcn2 expression (Tpcn1/2(-/-)), we show
      that the loss of endogenous TPCs abolished NAADP-dependent Ca(2+) responses as
      assessed by single-cell Ca(2+) imaging or patch-clamp of single endo-lysosomes.
      In contrast, currents stimulated by PI(3,5)P2 were only partially dependent on
      TPCs. In Tpcn1/2(-/-) cells, NAADP sensitivity was restored by re-expressing wild
      type TPCs, but not by mutant versions with impaired Ca(2+)-permeability, nor by
      TRPML1. Another mouse line formerly reported as TPC-null likely expresses
      truncated TPCs, but we now show that these truncated proteins still support NAADP
      induced Ca(2+) release. High-affinity [(32)P]NAADP binding still occurs in
      Tpcn1/2(-/-) tissue, suggesting that NAADP regulation is conferred by an
      accessory protein. Altogether, our data establish TPCs as Ca(2+)-permeable
      channels indispensable for NAADP signalling. 

PMID- 25872776
TI  - Persistent Occiput Posterior position - OUTcomes following manual rotation (POP
      OUT): study protocol for a randomised controlled trial.
AB  - BACKGROUND: Occiput posterior position is the most common malpresentation in
      labour, contributes to about 18% of emergency caesarean sections and is
      associated with a high risk of assisted delivery. Caesarean section is now a
      major contributing factor to maternal mortality and morbidity following
      childbirth in developed countries. Obstetric intervention by forceps and ventouse
      delivery is associated with complications to the maternal genital tract and to
      the neonate, respectively. There is level 2 evidence that prophylactic manual
      rotation reduces the caesarean section rate and assisted vaginal delivery. But
      there has been no adequately powered randomised controlled trial. This is a
      protocol for a double-blinded, multicentre, randomised controlled clinical trial
      to define whether this intervention decreases the operative delivery (caesarean
      section, forceps or vacuum delivery) rate. METHODS/DESIGN: Eligible participants
      will be (greater than or equal to) 37 weeks' with a singleton pregnancy and a
      cephalic presentation in the occiput posterior position on transabdominal
      ultrasound early in the second stage of labour. Based on a background risk of
      operative delivery of 68%, then for a reduction to 50%, an alpha value of 0.05
      and a beta value of 0.2, 254 participants will need to be enrolled. This study
      has been approved by the Ethics Review Committee (RPAH Zone) of the Sydney Local
      Health District, Sydney, Australia, and protocol number X110410. Participants
      with written consent will be randomised to either prophylactic manual rotation or
      a sham procedure. The primary outcome will be operative delivery (defined as
      vacuum, forceps and/or caesarean section deliveries). Secondary outcomes will be
      caesarean section, significant maternal mortality/morbidity and significant
      perinatal mortality/morbidity. Analysis will be by intention-to-treat. Primary
      and secondary outcomes will be compared using a chi-squared test. A logistic
      regression for the primary outcome will be undertaken to account for potential
      confounders. The results of the trial will be presented at one or more medical
      conferences. The trial will be submitted to peer review journals for
      consideration for publication. There will be potential to incorporate the results
      into professional guidelines for obstetricians and midwives. TRIAL REGISTRATION:
      The Australian New Zealand Clinical Trials Registry ACTRN12612001312831 . Trial
      registered 12 December 2012.

PMID- 25872777
TI  - Mortality of a cohort of workers in Great Britain with blood lead measurements.
AB  - OBJECTIVES: We examined the mortality of a historic cohort of workers in Great
      Britain with measured blood lead levels (BLLs). METHODS: SMRs were calculated
      with the population of Great Britain as the external comparator. Trends in
      mortality with mean and maximum BLLs and assessed lead exposure were examined
      using Cox regression. RESULTS: Mean follow-up length among the 9122 study
      participants was 29.2 years and 3466 deaths occurred. For all causes and all
      malignant neoplasms, the SMRs were statistically significantly raised. For
      disease groups of a priori interest, the SMR was significantly raised for lung
      cancer but not for stomach, brain, kidney, bladder or oesophageal cancers. The
      SMR was not increased for non-malignant kidney disease but was borderline
      significantly increased for circulatory diseases, for ischaemic heart disease
      (IHD) and cerebrovascular disease (CVD). No significant trends with exposure were
      observed for the cancers of interest, but for circulatory diseases and IHD, there
      was a statistically significant trend for increasing HR with mean and maximum
      BLLs. CONCLUSIONS: This study found an excess of lung cancer, although the risk
      was not clearly associated with increasing BLLs. It also found marginally
      significant excesses of IHD and CVD, the former being related to mean and maximum
      BLLs. The finding for IHD may have been due to lead, but could also have been due
      to other dust exposure associated with lead exposure and possibly tobacco
      smoking. Further work is required to clarify this and the carcinogenicity of
      lead.

PMID- 25872779
TI  - Faith healers, myths and deaths.
AB  - Science and myth have been closely linked and argued upon by philosophers,
      educationalists, scientists, enthusiasts and the general public. Faith healing,
      when added as an adjuvant or alternative aid to medical science, will not
      necessarily be confined to mere arguments and debates but may also give rise to
      series of complications, medical emergencies and even result in death. We present
      an unusual case where reliance on faith healing led to the death of a young man. 

PMID- 25872778
TI  - Fbxl10 overexpression in murine hematopoietic stem cells induces leukemia
      involving metabolic activation and upregulation of Nsg2.
AB  - We previously reported that deficiency for Samd9L, which was cloned as a
      candidate gene for -7/7q- syndrome, accelerated leukemia cooperatively with
      enhanced expression of a histone demethylase: F-box and leucine-rich repeat
      protein 10 (Fbxl10, also known as Jhdm1b, Kdm2b, and Ndy1). To further
      investigate the role of Fbxl10 in leukemogenesis, we generated transgenic (Tg)
      mice that overexpress Fbxl10 in hematopoietic stem cells (HSCs). Interestingly,
      Fbxl10 Tg mice developed myeloid or B-lymphoid leukemia with complete penetrance.
      HSCs from the Tg mice exhibited an accelerated G0/G1-to-S transition with a
      normal G0 to G1 entry, resulting in pleiotropic progenitor cell expansion. Fbxl10
      Tg HSCs displayed enhanced expression of neuron-specific gene family member 2
      (Nsg2), and forced expression of Nsg2 in primary bone marrow cells resulted in
      expansion of immature cells. In addition, the genes involved in mitochondrial
      oxidative phosphorylation were markedly enriched in Fbxl10 Tg HSCs, coupled with
      increased cellular adenosine 5'-triphosphate levels. Moreover, chromatin
      immunoprecipitation followed by sequencing analysis demonstrated that Fbxl10
      directly binds to the regulatory regions of Nsg2 and oxidative phosphorylation
      genes. These findings define Fbxl10 as a bona fide oncogene, whose deregulated
      expression contributes to the development of leukemia involving metabolic
      proliferative advantage and Nsg2-mediated impaired differentiation. 

PMID- 25872780
TI  - Frequency of pneumothorax and haemothorax after primary open versus closed
      implantation strategies for insertion of a totally implantable venous access port
      in oncological patients: study protocol for a randomised controlled trial.
AB  - BACKGROUND: The insertion of central venous access devices, such as totally
      implantable venous access ports (TIVAPs), is routine in patients who need a safe
      and permanent venous access. The number of port implantations is increasing due
      to the development of innovative adjuvant and neo-adjuvant therapies. Currently,
      two different strategies are being routinely used: surgical cut-down of the
      cephalic vein (vena section) and direct puncture of the subclavian vein. The aim
      of this trial is to identify the strategy for the implantation of TIVAPs with the
      lowest risk of pneumothorax and haemothorax. METHODS/DESIGN: The PORTAS-3 trial
      is designed as a multicentre, randomised controlled trial to compare two
      implantation strategies. A total of 1,154 patients will be randomised after
      giving written informed consent. Patients must be over 18 years of age and
      scheduled for primary implantation of a TIVAP on the designated side. The primary
      endpoint will be the frequency of pneumothorax and haemothorax after insertion of
      a TIVAP by one of two different strategies. The experimental intervention is as
      follows: open strategy, defined as surgical cut-down of the cephalic vein,
      supported by a rescue technique if necessary, and in the case of failure, direct
      puncture of the subclavian vein. The control intervention is as follows: direct
      puncture of the subclavian vein using the Seldinger technique guided by
      sonography, fluoroscopy or landmark technique. The trial duration is
      approximately 36 months, with a recruitment period of 18 months and a follow-up
      period of 30 days. DISCUSSION: The PORTAS-3 trial will compare two different
      TIVAP implantation strategies with regard to their individual risk of
      postoperative pneumothorax and haemothorax. Since TIVAP implantation is one of
      the most common procedures in general surgery, the results will be of interest
      for a large community of surgeons as well as oncologists and general
      practitioners. The pragmatic trial design ensures that the results will be
      generalizable to a wide range of patients. TRIAL REGISTRATION: The trial protocol
      was registered on 28 August 2014 with the German Clinical Trials Register
      (DRKS00004900) . The World Health Organization's Universal Trial Number is U1111
      1142-4420.

PMID- 25872781
TI  - Twisting phonons in complex crystals with quasi-one-dimensional substructures.
AB  - A variety of crystals contain quasi-one-dimensional substructures, which yield
      distinctive electronic, spintronic, optical and thermoelectric properties. There
      is a lack of understanding of the lattice dynamics that influences the properties
      of such complex crystals. Here we employ inelastic neutron scatting measurements
      and density functional theory calculations to show that numerous low-energy
      optical vibrational modes exist in higher manganese silicides, an example of such
      crystals. These optical modes, including unusually low-frequency twisting motions
      of the Si ladders inside the Mn chimneys, provide a large phase space for
      scattering acoustic phonons. A hybrid phonon and diffuson model is proposed to
      explain the low and anisotropic thermal conductivity of higher manganese
      silicides and to evaluate nanostructuring as an approach to further suppress the
      thermal conductivity and enhance the thermoelectric energy conversion efficiency.
      This discovery offers new insights into the structure-property relationships of a
      broad class of materials with quasi-one-dimensional substructures for various
      applications. 

PMID- 25872782
TI  - Electromagnetic guided bedside or endoscopic placement of nasoenteral feeding
      tubes in surgical patients (CORE trial): study protocol for a randomized
      controlled trial.
AB  - BACKGROUND: Gastroparesis is common in surgical patients and frequently leads to
      the need for enteral tube feeding. Nasoenteral feeding tubes are usually placed
      endoscopically by gastroenterologists, but this procedure is relatively
      cumbersome for patients and labor-intensive for hospital staff. Electromagnetic
      (EM) guided bedside placement of nasoenteral feeding tubes by nurses may reduce
      patient discomfort, workload and costs, but randomized studies are lacking,
      especially in surgical patients. We hypothesize that EM guided bedside placement
      of nasoenteral feeding tubes is at least as effective as endoscopic placement in
      surgical patients, at lower costs. METHODS/DESIGN: The CORE trial is an
      investigator-initiated, parallel-group, pragmatic, multicenter randomized
      controlled non-inferiority trial. A total of 154 patients admitted to
      gastrointestinal surgical wards in five hospitals, requiring nasoenteral feeding,
      will be randomly allocated to undergo EM guided or endoscopic nasoenteral feeding
      tube placement. Primary outcome is reinsertion of the feeding tube, defined as
      the insertion of an endoscope or tube in the nose/mouth and esophagus for
      (re)placement of the feeding tube (e.g. after failed initial placement or
      dislodgement or blockage of the tube). Secondary outcomes include patient
      reported outcomes, costs and tube (placement) related complications. DISCUSSION:
      The CORE trial is designed to generate evidence on the effectiveness of EM guided
      placement of nasoenteral feeding tubes in surgical patients and the impact on
      costs as compared to endoscopic placement. The trial potentially offers a strong
      argument for wider implementation of this technique as method of choice for
      placement of nasoenteral feeding tubes. TRIAL REGISTRATION: Dutch Trial Register:
      NTR4420 , date registered 5-feb-2014.

PMID- 25872783
TI  - Ferromagnetism in layered metastable 1T-CrTe2.
AB  - We have synthesized for the first time the metastable compound 1T-CrTe2. We have
      done its complete structural characterization and measured its magnetization,
      specific heat and electrical resistivity between 4 and 330 K. We have also
      performed detailed band structure calculations. We have found that it
      crystallizes in the CdI2 structure type and that its electrical resistance
      follows a metallic behaviour below room temperature. Its magnetization and
      specific heat curves show that the compound has a transition to a ferromagnetic
      state at TC = 310 K, with the magnetic moments ordered parallel to the basal
      plane. From the specific heat measurements and the ferromagnetic solutions
      obtained from our DFT calculations, we conclude that the ferromagnetism is of
      itinerant nature. 

PMID- 25872784
TI  - Activating transcription factor 3 is overexpressed in human glioma and its
      knockdown in glioblastoma cells causes growth inhibition both in vitro and in
      vivo.
AB  - Glioblastomas are highly malignant gliomas that are extremely invasive with high
      rates of recurrence and mortality. It has been reported that activating
      transcription factor 3 (ATF3) is expressed in elevated levels in multiple
      malignant tumors. The purpose of this study was to investigate the function of
      ATF3 in the development of glioma and its clinical significance.
      Immunohistochemical staining, western blot analysis and RT-qPCR revealed that the
      mRNA and protein levels of ATF3 and matrix metalloproteinase 2 (MMP2) were higher
      in the glioma than in the normal human brain tissues, and that their levels were
      proportional to the pathological grades. By contrast, the mRNA and protein levels
      of mammary serine protease inhibitor (maspin; SERPINB5) were significantly lower
      in the glioma than in the normal brain tissue, and maspin expression was
      inversely proportional to the glioma pathological grade. The transfection of
      U373MG glioblastoma cells with ATF3-siRNA induced a number of changes in cell
      behavior; the cell proliferative activity was decreased and flow cytometry
      revealed an increased proportion of cells arrested in the G0/G1 phase of the cell
      cycle. In addition, TUNEL staining indicated an increased proportion of cells
      undergoing apoptosis and Transwell assays revealed impaired cell mobility. The
      sizes of the tumors grown as xenografts in nude mice were also significantly
      reduced by treatment of host mice with ATF3-siRNA. Taken together, these results
      suggest that ATF3 promotes the progression of human gliomas.

PMID- 25872785
TI  - Inhibition of TMEM45A suppresses proliferation, induces cell cycle arrest and
      reduces cell invasion in human ovarian cancer cells.
AB  - The association of TMEM45A with various cancers has been recently reported.
      However, the biological function of TMEM45A in ovarian cancer remains unclear.
      The present study aimed to elucidate the role of TMEM45A in regulating the
      biological behavior of ovarian cancer cells. We compared the expression of
      TMEM45A between ovarian cancer tissues and normal tissues based on RNA-sequencing
      data of the ovarian cancer cohort from The Cancer Genome Atlas (TCGA) project and
      our real-time PCR data from 25 pairs of ovarian cancer and their matched non
      cancerous tissue samples. The expression of TMEM45A was then suppressed in two
      ovarian cancer cell lines, HO-8910 and A2780, by RNA interference. Cell
      proliferation, cell cycle distribution, adhesion and invasive ability were then
      detected using the Cell Counting Kit-8 assay (CCK-8), propidium iodide (PI)
      staining, and cell adhesion and Transwell assays, respectively. In addition, the
      mRNA and protein levels of transforming growth factor-beta (TGF-beta1 and TGF
      beta2), Ras homolog family member A (RhoA) and Rho-associated kinase 2 (ROCK2)
      were detected with real-time PCR and western blotting, respectively. TCGA data
      and our real-time PCR results demonstrated the overexpression of TMEM45A in
      ovarian cancer. Silencing of TMEM45A significantly inhibited cell proliferation
      and significantly increased the cell population in the G1 phase. Moreover,
      knockdown of TMEM45A also inhibited cell adhesion as well as cell invasion. More
      importantly, suppression of TMEM45A notably downregulated the expression of TGF
      beta1, TGF-beta2, RhoA and ROCK2. In conclusion, TMEM45A may function as an
      oncogene for ovarian cancer, and inhibition of TMEM45A may be a therapeutic
      strategy for ovarian cancer.

PMID- 25872786
TI  - A comparison of service use by people with dementia in two samples a decade
      apart.
AB  - Investment in improving community-based dementia care is underway in the United
      Kingdom, but we do not know how well it meets the needs of people with dementia
      and those who care for them. The aim of this study was to explore the service use
      and reported unmet needs of people with dementia in two samples recruited a
      decade apart. We interviewed 122 carers from Central Scotland and London in 2000
      2001 and 84 carers from South-East England in 2010-2011 using the same interview
      schedule. The two samples of carers had similar demographics. The later groups
      were more likely to be spouses, slightly older, not working, ethnically diverse,
      have better perceived health and better access to a car. The people with dementia
      in each sample had similar characteristics and levels of disability. Carers in
      the later sample reported more met need for activities of daily living, although
      up to a third were still not getting sufficient help with some activities. Nearly
      half of both samples reported verbal aggression and nearly a fifth physical
      aggression, yet most have not received advice on how to manage this. There is a
      more evident role of the practice nurse ( p = 0.01) and less evident use of
      community nurses ( p = 0.0005), psychiatric nurses ( p = 0.006) and health
      visitors ( p = 0.0003) in the more recent sample.

PMID- 25872787
TI  - Tafamidis in transthyretin amyloid cardiomyopathy: effects on transthyretin
      stabilization and clinical outcomes.
AB  - BACKGROUND: Transthyretin (TTR) amyloidosis is a progressive systemic disorder
      caused by misfolded TTR monomers that cumulatively deposit in the heart and
      systemically as amyloid. METHODS AND RESULTS: This phase 2 open-label trial
      evaluated the stabilization of TTR tetramers using 20 mg of tafamidis daily at
      week 6 (primary end point), month 6, and month 12, as well as safety of tafamidis
      treatment and efficacy with respect to progression of TTR amyloid cardiomyopathy.
      Thirty-one wild-type patients (median age, 76.7 years; 93.5% men) with a median
      disease duration of 55.6 months and mild to moderate heart failure (96.8%; New
      York Heart Association, classes I-II) were enrolled. Thirty of 31 patients
      (96.8%) achieved TTR stabilization after 6 weeks and 25 of 28 patients (89.3%)
      after 12 months. After 12 months of treatment, 3 patients discontinued
      prematurely, 2 patients died, 7 patients were hospitalized because of
      cardiovascular events, 20 of 28 patients demonstrated preserved New York Heart
      Association classification status, but 15 of 31 (48.4%) patients had clinical
      progression (eg, admission for cardiac failure, atrial fibrillation, and
      syncope). N-terminal prohormone brain natriuretic peptide levels did not increase
      significantly over time, troponin I and troponin T increased moderately, and no
      consistent clinically relevant changes were seen in echocardiographic cardiac
      assessments. Tafamidis treatment was generally well tolerated although 7 of 31
      patients had bouts of diarrhea. CONCLUSIONS: Tafamidis treatment effectively
      achieved and maintained TTR stabilization and was well tolerated. The absence of
      significant changes in most biochemical and echocardiographic parameters suggests
      that further evaluation of tafamidis in TTR amyloid cardiomyopathy is warranted.
      CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique
      identifier: NCT00694161.

PMID- 25872788
TI  - Alcohol and incident heart failure among middle-aged and elderly men: cohort of
      Swedish men.
AB  - BACKGROUND: Compared with no alcohol consumption, heavy alcohol intake is
      associated with a higher rate of heart failure (HF) whereas light-to-moderate
      intake may be associated with a lower rate. However, several prior studies did
      not exclude former drinkers, who may have changed alcohol consumption in response
      to diagnosis. This study aimed to investigate the association between alcohol
      intake and incident HF. METHODS AND RESULTS: We conducted a prospective cohort
      study of 33 760 men aged 45 to 79 years with no HF, diabetes mellitus, or
      myocardial infarction at baseline participating in the Cohort of Swedish Men
      Study. We excluded former drinkers. At baseline, participants completed a food
      frequency questionnaire and reported other characteristics. HF was defined as
      hospitalization for or death from HF, ascertained by Swedish inpatient and cause
      of-death records from January 1, 1998, through December 31, 2011. We constructed
      Cox proportional hazards models to estimate multivariable-adjusted incidence rate
      ratios. During follow-up, 2916 men were hospitalized for (n=2139) or died (n=777)
      of incident HF. There was a U-shaped relationship between total alcohol intake
      and incident HF (P=0.0004). There was a nadir at light-to-moderate alcohol
      intake: consuming 7 to <14 standard drinks per week was associated with a 19%
      lower multivariable-adjusted rate of HF compared with never drinking (incidence
      rate ratio, 0.81; 95% confidence interval, 0.69-0.96). CONCLUSIONS: In this
      cohort of Swedish men, there was a U-shaped relationship between alcohol
      consumption and HF incidence, with a nadir at light-to-moderate intake. Heavy
      intake did not seem protective.

PMID- 25872789
TI  - SMART: physical activity and cerebral metabolism in older people: study protocol
      for a randomised controlled trial.
AB  - BACKGROUND: Physical activity exerts a variety of long-term health benefits in
      older adults. In particular, it is assumed to be a protective factor against
      cognitive decline and dementia. METHODS/DESIGN: Randomised controlled assessor
      blinded 2-armed trial (n = 60) to explore the exercise- induced neuroprotective
      and metabolic effects on the brain in cognitively healthy older adults.
      Participants (age >= 65), recruited within the setting of assisted living
      facilities and newspaper advertisements are allocated to a 12-week individualised
      aerobic exercise programme intervention or a 12-week waiting control group. Total
      follow-up is 24 weeks. The main outcome is the change in cerebral metabolism as
      assessed with Magnetic Resonance Spectroscopic Imaging reflecting changes of
      cerebral N-acetyl-aspartate and of markers of neuronal energy reserve. Imaging
      also measures changes in cortical grey matter volume. Secondary outcomes include
      a broad range of psychometric (cognition) and movement-related parameters such as
      nutrition, history of physical activity, history of pain and functional
      diagnostics. Participants are allocated to either the intervention or control
      group using a computer-generated randomisation sequence. The exercise
      physiologist in charge of training opens sealed and opaque envelopes and informs
      participants about group allocation. For organisational reasons, he schedules the
      participants for upcoming assessments and exercise in groups of five. All
      assessors and study personal other than exercise physiologists are blinded.
      DISCUSSION: Magnetic Resonance Spectroscopic Imaging gives a deeper insight into
      mechanisms of exercise-induced changes in brain metabolism. As follow-up lasts
      for 6 months, this study is able to explore the mid-term cerebral metabolic
      effects of physical activity assuming that an individually tailored aerobic
      ergometer training has the potential to counteract brain ageing. TRIAL
      REGISTRATION: NCT02343029 (clinicaltrials.gov; 12 January 2015).

PMID- 25872790
TI  - Safety and efficacy of colistin versus meropenem in the empirical treatment of
      ventilator-associated pneumonia as part of a macro-project funded by the Seventh
      Framework Program of the European Commission studying off-patent antibiotics:
      study protocol for a randomized controlled trial.
AB  - BACKGROUND: Ventilator-associated pneumonia (VAP) is one of the most common and
      severe hospital-adquired infections, and multidrugresistant gram-negative bacilli
      (MDR-GNB) constitute the main etiology in many countries. Inappropriate empiric
      antimicrobial treatment is associated with increased mortality. In this context,
      the empirical treatment of choice for VAP is unknown. Colistin, is now the
      antimicrobial with greatest in vitro activity against MDR-GNB. METHODS/DESIGN:
      The MagicBullet clinical trial is an investigator-driven clinical study, funded
      by the Seventh Framework Program of the European Commission. This is designed as
      a phase IV, randomized, controlled, open label, non-inferiority and international
      trial to assess the safety and efficacy of colistin versus meropenem in late
      onset VAP. The study is conducted in a total of 32 centers in three European
      countries (Spain, Italy and Greece) with specific high incidences of infections
      caused by MDR-GNB. Patients older than 18 years who develop VAP with both
      clinical and radiological signs, and are on mechanical ventilation for more than
      96 hours, or less than 96 hours but with previous antibiotic treatment plus one
      week of hospitalization, are candidates for inclusion in the study. A total
      sample size of 496 patients will be randomized according to a severity clinical
      score (at the time of VAP diagnosis in a 1:1 ratio to receive either colistin 4.5
      MU as a loading dose, followed by 3 MU every eight hours (experimental arm), or
      meropenem 2 g every eight hours (control arm), both combined with levofloxacin.
      Mortality from any cause at 28 days will be considered as the main outcome.
      Clinical and microbiological cure will be evaluated at 72 hours, eight days, the
      finalization of antibiotic treatment, and 28 days of follow-up. The efficacy
      evaluation will be performed in every patient who receives at least one study
      treatment drug, and with etiologic diagnosis of VAP, intention-to-treat
      population and per protocol analysis will be performed. DISCUSSION: Currently,
      there is no study being undertaken which analyzes empiric treatment of (VAP) with
      a suspicion of multi-resistance. Colistin, an off-patent antibiotic
      commercialized for more than 60 years, could widen the antibiotic alternatives
      for a high-mortality illness aggravated by antibiotic resistance. TRIAL
      REGISTRATION: This trial is registered with ClinicalTrials.gov (identifier:
      NCT01292031 ; registered on 29 June 2012) and EudraCT (identifier: 2010-023310
      31; registered on 7 February 2011).

PMID- 25872791
TI  - Antiprotozoal Nitazoxanide Derivatives: Synthesis, Bioassays and QSAR Study
      Combined with Docking for Mechanistic Insight.
AB  - In view of the serious health problems concerning infectious diseases in heavily
      populated areas, we followed the strategy of lead compound diversification to
      evaluate the near-by chemical space for new organic compounds. To this end,
      twenty derivatives of nitazoxanide (NTZ) were synthesized and tested for activity
      against Entamoeba histolytica parasites. To ensure drug-likeliness and activity
      relatedness of the new compounds, the synthetic work was assisted by a
      quantitative structure-activity relationships study (QSAR). Many of the inherent
      downsides - well-known to QSAR practitioners - we circumvented thanks to
      workarounds which we proposed in prior QSAR publication. To gain further
      mechanistic insight on a molecular level, ligand-enzyme docking simulations were
      carried out since NTZ is known to inhibit the protozoal pyruvate ferredoxin
      oxidoreductase (PFOR) enzyme as its biomolecular target. 

PMID- 25872792
TI  - Novel graphene foam composite with adjustable sensitivity for sensor
      applications.
AB  - In this study, free-standing graphene foam (GF) was developed by a three-step
      method: (1) vacuum-assisted dip-coating of nickel foam (Ni-F) with graphene oxide
      (GO), (2) reduction of GO to reduced graphene oxide (rGO), and then (3) etching
      out the nickel scaffold. Pure GF samples were tested for their morphology,
      chemistry, and mechanical integrity. GF mimics the microstructure of Ni-F while
      individual bones of GF were hollow, because of the complete removal of nickel.
      The GF-PDMS composites were tested for their ability to sense both compressive
      and bending strains in the form of change in electrical resistance. The composite
      showed different sensitivity to bending and compression. Upon applying a 30%
      compressive strain on the GF-PDMS composite, its resistance increased to ~120% of
      its original value. Similarly, bending a sample to a radius of 1 mm caused the
      composite to change its resistance to ~52% of its original resistance value. The
      relative change in resistance of the composite by an applied pressure/strain can
      be tuned to considerably different values by heat-treating the GF at different
      temperatures prior to infusing PDMS into its scaffold. Upon heat treating the GF
      at 800  degrees C prior to PDMS infusion, the GF-PDMS demonstrated ~10 times
      better sensitivity than the untreated sample for a compressive strain of 20%. The
      composite was also tested for its ability to retain a change in electrical
      resistance when a brief load/strain is applied. The GF-PDMS composite was tested
      for at least 500 cycles under compressive cyclic loading and showed good
      electromechanical durability. Finally, it was demonstrated that the composite can
      be used to measure human blood pressure when attached to human skin. 

PMID- 25872793
TI  - Mice lacking glutamate carboxypeptidase II develop normally, but are less
      susceptible to traumatic brain injury.
AB  - Glutamate carboxypeptidase II (GCPII) is a transmembrane zinc metallopeptidase
      found mainly in the nervous system, prostate and small intestine. In the nervous
      system, glia-bound GCPII mediates the hydrolysis of the neurotransmitter N
      acetylaspartylglutamate (NAAG) into glutamate and N-acetylaspartate. Inhibition
      of GCPII has been shown to attenuate excitotoxicity associated with enhanced
      glutamate transmission under pathological conditions. However, different strains
      of mice lacking the GCPII gene are reported to exhibit striking phenotypic
      differences. In this study, a GCPII gene knockout (KO) strategy involved removing
      exons 3-5 of GCPII. This generated a new GCPII KO mice line with no overt
      differences in standard neurological behavior compared to their wild-type (WT)
      littermates. However, GCPII KO mice were significantly less susceptible to
      moderate traumatic brain injury (TBI). GCPII gene KO significantly lessened
      neuronal degeneration and astrocyte damage in the CA2 and CA3 regions of the
      hippocampus 24 h after moderate TBI. In addition, GCPII gene KO reduced TBI
      induced deficits in long-term spatial learning/memory tested in the Morris water
      maze and motor balance tested via beam walking. Knockout of the GCPII gene is not
      embryonic lethal and affords histopathological protection with improved long-term
      behavioral outcomes after TBI, a result that further validates GCPII as a target
      for drug development consistent with results from studies using GCPII peptidase
      inhibitors.

PMID- 25872796
TI  - Preschoolers use phrasal prosody online to constrain syntactic analysis.
AB  - Two experiments were conducted to investigate whether young children are able to
      take into account phrasal prosody when computing the syntactic structure of a
      sentence. Pairs of French noun/verb homophones were selected to create locally
      ambiguous sentences ([la petite ferme] [est tres jolie] 'the small farm is very
      nice' vs. [la petite] [ferme la fenetre] 'the little girl closes the window'-
      brackets indicate prosodic boundaries). Although these sentences start with the
      same three words, ferme is a noun (farm) in the former but a verb (to close) in
      the latter case. The only difference between these sentence beginnings is the
      prosodic structure, that reflects the syntactic structure (with a prosodic
      boundary just before the critical word when it is a verb, and just after it when
      it is a noun). Crucially, all words following the homophone were masked, such
      that prosodic cues were the only disambiguating information. Children
      successfully exploited prosodic information to assign the appropriate syntactic
      category to the target word, in both an oral completion task (4.5-year-olds,
      Experiment 1) and in a preferential looking paradigm with an eye-tracker (3.5
      year-olds and 4.5-year-olds, Experiment 2). These results show that both groups
      of children exploit the position of a word within the prosodic structure when
      computing its syntactic category. In other words, even younger children of 3.5
      years old exploit phrasal prosody online to constrain their syntactic analysis.
      This ability to exploit phrasal prosody to compute syntactic structure may help
      children parse sentences containing unknown words, and facilitate the acquisition
      of word meanings.

PMID- 25872794
TI  - Early warning scoring systems versus standard observations charts for wards in
      South Africa: a cluster randomized controlled trial.
AB  - BACKGROUND: On South African public hospital wards, observation charts do not
      incorporate early warning scoring (EWS) systems to inform nurses when to summon
      assistance. The aim of this trial was to test the impact of a new chart
      incorporating a modified EWS (MEWS) system and a linked training program on
      nurses' responses to clinical deterioration (primary outcome). Secondary outcomes
      were: numbers of patients with vital signs recordings in the first eight
      postoperative hours; number of times each vital sign was recorded; and nurses'
      knowledge. METHODS/DESIGN: A pragmatic, parallel-group, cluster randomized,
      controlled clinical trial of intervention versus standard care was conducted in
      three intervention and three control adult surgical wards in an 867-bed public
      hospital in Cape Town, between March and July 2010; thereafter the MEWS chart was
      withdrawn. A total of 50 out of 122 nurses in full-time employment participated.
      From 1,427 case notes, 114 were selected by randomization for assessment. The
      MEWS chart was implemented in intervention wards. Control wards delivered
      standard care, without training. Case notes were reviewed two weeks after the
      trial's completion. Knowledge was assessed in both trial arms by blinded
      independent marking of written tests before and after training of nurses in
      intervention wards. Analyses were undertaken with IBM SPSS software on an
      intention-to-treat basis. RESULTS: Patients in trial arms were similar.
      Introduction of the MEWS was not associated with statistically significant
      changes in responses to clinical deterioration (50 of 57 received no assistance
      versus 55 of 57, odds ratio (OR): 0.26, 95% confidence interval (CI): 0.05 to
      1.31), despite improvement in nurses' knowledge in intervention wards. More
      patients in intervention than control wards had recordings of respiratory rate
      (27 of 57 versus 2 of 57, OR: 24.75, 95% CI: 5.5 to 111.3) and recordings of all
      seven parameters (5 of 57 versus 0 of 57 patients, risk estimate: 1.10, 95% CI:
      1.01 to 1.2). CONCLUSIONS: A MEWS chart and training program enhanced recording
      of respiratory rate and of all parameters, and nurses' knowledge, but not nurses'
      responses to patients who triggered the MEWS reporting algorithm. TRIAL
      REGISTRATION: This trial was registered with the Pan African Clinical Trials
      Registry (identifier: PACTR201309000626545 ) on 9 September 2013.

PMID- 25872797
TI  - Hydrogen sulfide attenuates IL-1beta-induced inflammatory signaling and
      dysfunction of osteoarthritic chondrocytes.
AB  - Inflammatory cytokines are crucial factors in the onset of osteoarthritis (OA).
      The pro-inflammatory cytokine, interleukin-1beta (IL-1beta), is capable of
      stimulating a few cartilage degradation mediators and is of importance to the
      pathogenesis of OA. It has been demonstrated that hydrogen sulfide (H2S) exerts
      an inhibitory effect on inflammation. Thus, in the present study, we aimed to
      investigate the therapeutic effects of H2S in OA. For this purpose, an in vitro
      model of cartilage inflammation was created. Human OA chondrocytes were cultured
      and pre-treated with H2S (0.06-1.5 mM) with or without IL-1beta (10 ng/ml) and
      then Griess reagent was used to quantify the production of nitric oxide (NO).
      Using enzyme-linked immunosorbent assay, we quantified the production of
      prostaglandin E2 (PGE2) and matrix metalloproteinase-13 (MMP-13). In addition, we
      determined the gene expression of inducible nitric oxide synthase (iNOS),
      cyclooxygenase-2 (COX-2) and MMP-13 using reverse transcription-quantitative
      polymerase chain reaction and the expression of signaling molecules related to
      mitogen-activated protein kinases (MAPKs) and nuclear factor-kappaB (NF-kappaB)
      by western blot analysis. Our results revealed that H2S markedly reversed the
      effects of IL-1beta on the gene expression of COX-2, MMP-13 and iNOS and on the
      production of MMP-13, PGE2 and NO. In addition, H2S inhibited the activation of
      the extracellular signal-regulated kinase (ERK)/IkappaBalpha/NF-kappaB pathway
      which was induced by IL-1beta. On the whole, the results of the present study
      suggest that H2S exerts chondroprotective effects. Thus, H2S may have potential
      for use in the treatment of patients suffering from OA.

PMID- 25872798
TI  - Identification of Low-Risk Adult Congenital LQTS Patients.
AB  - INTRODUCTION: To date, most risk stratification studies in long-QT syndrome
      (LQTS) have focused on identification of high-risk subjects. Current data on the
      long-term clinical course of low-risk adult LQTS patients are limited. METHODS
      AND RESULTS: Patients in this study were from the Rochester-based LQTS Registry.
      We hypothesized that long-term survival of LQT1-2 patients with QTc <500
      milliseconds and no cardiac symptoms before age 20 (n = 523) would be similar to
      that of their unaffected genotype-negative family members (n = 1,134). Kaplan
      Meier survival analysis and multivariate Cox proportional hazards regression
      models were used to evaluate the incidence and risk of all-cause mortality in the
      study population. The low-risk LQTS study group comprised 27% (523/1,919) of
      genetically confirmed LQTS Registry patients alive at age 20. The cumulative
      probability of all-cause mortality between age 20 and 65 was similar in the low
      risk LQTS group and the genotype-negative control group (4.3% and 4.4%,
      respectively at age 65; P = 0.49 for overall difference). Multivariate analysis
      showed no significant difference in the risk of all-cause mortality between the 2
      groups (HR = 0.89; 95% CI 0.33-2.43, P = 0.82). Consistent results were revealed
      in subgroup analyses in female and male LQTS patients and in patients with
      genetically identified LQT1 and LQT2 mutations. CONCLUSIONS: We identified a
      sizeable proportion of low-risk, adult LQTS patients with no cardiac symptoms
      before age 20 and QTc<500 milliseconds who had 45-year survival similar to
      unaffected family members.

PMID- 25872799
TI  - Transabdominal ultrasound measurement of rectal diameter is dependent on time to
      defecation in constipated children.
AB  - AIM: To study whether diurnal variations and time in relation to defecation has
      to be taken into account when measurements of rectal diameter are used to
      determine faecal impaction in constipated children. METHODS: Repeated ultrasound
      measures of rectal diameter were performed in 28 children (14 constipated/14
      healthy, aged between 4 and 12 years) every third hour during 24 h. After
      defecation, three additional scans were performed at 1-h intervals. RESULTS: No
      diurnal variation in rectal diameter was found in the healthy group. In the
      constipated group, mean rectal diameter was significantly larger at 2 pm (P =
      0.038) and 5 pm (P = 0.006). There were significant differences between rectal
      diameter in the healthy group and the constipated group at 2 pm (P = 0.016) and 5
      pm (P = 0.027). When we omitted the rectal diameter of five constipated children
      who had their first bowel movement after 5 pm, there were no difference between
      groups (2 pm (P = 0.103)/5 pm (P = 0.644) ). Only in the constipated group,
      rectal diameter exceeded 3 cm without the patients feeling the urge to defecate.
      CONCLUSION: We found no independent daily variation in either group without
      relation to defecation. There was a relation between defecation and changes in
      rectal diameter in both healthy children and constipated children during
      maintenance treatment.Asking for defecation signals before scanning should be
      considered a routine question, and a positive answer should cause postponement of
      the scan.

PMID- 25872800
TI  - Successful Semi-Ambulatory Veno-Arterial Extracorporeal Membrane Oxygenation
      Bridge to Heart-Lung Transplantation in a Very Small Child.
AB  - Lung transplantation (LTx) may be denied for children on extracorporeal membrane
      oxygenation (ECMO) due to high risk of cerebral hemorrhage. Rarely has successful
      LTx been reported in children over 10 years of age receiving awake or ambulatory
      veno-venous ECMO. LTx following support with ambulatory veno-arterial ECMO (VA
      ECMO) in children has never been reported to our knowledge. We present the case
      of a 4-year-old, 12-kg child with heritable pulmonary artery hypertension and
      refractory right ventricular failure. She was successfully bridged to heart-lung
      transplantation (HLTx) using ambulatory VA ECMO. Initial resuscitation with
      standard VA ECMO was converted to an ambulatory circuit using Berlin heart
      cannulae. She was extubated and ambulating around her bed while on VA ECMO for 40
      days. She received an HLTx from an oversized marginal lung donor. Despite a
      cardiac arrest and Grade 3 primary graft dysfunction, she made a full recovery
      without neurological deficits. She achieved 104% force expiratory volume in 1 s
      33 months post-HLTx. Ambulatory VA ECMO may be a useful strategy to bridge very
      young children to LTx or HLTx. Patient tailored ECMO cannulation, minimization of
      hemorrhage, and thrombosis risks while on ECMO contributed to a successful HLTx
      in our patient. 

PMID- 25872801
TI  - Infusion of endothelial progenitor cells ameliorates liver injury in mice after
      haematopoietic stem cell transplantation.
AB  - BACKGROUND & AIMS: Injury to liver sinusoidal endothelial cells (LSECs) is
      thought to be the initial factor for Hepatic veno-occlusive disease, a severe
      complication after haematopoietic stem cell transplantation (HSCT). Endothelial
      progenitor cells (EPCs) have the capacity to differentiate into endothelial cells
      and play a critical role in vasculogenesis, tissue regeneration and repair.
      Whether EPCs infusion ameliorates LSECs injury remains unclear. The aim of this
      study was to evaluate the effects of EPCs on liver injury in mice after HSCT.
      METHODS: Mice received HSCT without or with EPCs infusion (HSCT + EPCs).
      Untreated mice were used as control. Liver and whole blood were collected post
      HSCT and used for the analysis of pathology of liver sinusoidal endothelial cells
      (LSECs) and hepatocytes, liver ultrastructure, function, level of IL-6, TNF-alpha
      and platelet activation. RESULTS: Severe LSECs injury, hepatocyte damage,
      abnormal liver function was observed in HSCT group. In addition, increased P
      selectin expression and secretion of IL-6, TNF-alpha was also found. However, all
      the above changes were alleviated in HSCT + EPCs at all the time points and
      normalized at the endpoint. Meanwhile, EPCs-induced repair of LSECs and
      hepatocytes was totally inhibited by the addition of anti-VE-cadherin antibody.
      CONCLUSIONS: EPCs infusion ameliorated the damage to LSECs and hepatocytes as
      well as reduced secretion of IL-6, TNF-alpha and inhibited platelet activation
      after HSCT, leading to improved liver function, suggesting EPCs might be a new
      therapeutic strategy in the prophylaxis of liver injury after HSCT.

PMID- 25872802
TI  - The effect of postpartum vitamin A supplementation on breast milk immune
      regulators and infant immune functions: study protocol of a randomized,
      controlled trial.
AB  - BACKGROUND: Because of limited impact on infant morbidity, mortality, and vitamin
      A status, the new guideline of the World Health Organization (WHO) does not
      recommend postpartum vitamin A supplementation (VAS) as a public health
      intervention in developing countries. However, breast milk contains numerous
      immune-protective components that are important for infant immune development,
      and several of these components are regulated by vitamin A. METHODS/DESIGN:
      Postpartum women are being enrolled within 3 days (d) of delivery at a maternity
      clinic located in a slum area of Dhaka city and randomized to one of four
      postpartum VAS regimens (32/group, total 128). The regimens are as follows: Group
      1: 200,000 IU VAS at <3 d and placebo at 6 weeks postpartum; Group 2: placebo at
      <3 d and 200,000 IU VAS at 6 weeks postpartum; Group 3: 200,000 IU VAS, both at
      <3 d and 6 weeks postpartum; Group 4: placebo, both at <3 d and 6 weeks
      postpartum. Breast milk samples at <3 d (before supplementation) and 4 months
      postpartum will be used to measure vitamin A and bioactive compounds. Infant
      blood samples at 2 and 4 months of age will be used to measure vitamin A, as well
      as innate and vaccine-specific immune responses. Dietary, anthropometric, and
      morbidity data are also being collected. DISCUSSION: This is the first placebo
      controlled randomized clinical trial of postnatal vitamin A supplementation to
      investigate the key bioactive compounds in breast milk, important for infant
      immunity, in relation to dose and time point of postpartum supplementation and
      whether such maternal supplementation improves infant immune status during the
      critical period of early infancy. TRIAL REGISTRATION: ClinicalTrials.gov:
      NCT02043223 , 5 December 2013.

PMID- 25872803
TI  - Force spectroscopy of multivalent binding of riboflavin-conjugated dendrimers to
      riboflavin binding protein.
AB  - Putative riboflavin receptors are considered as biomarkers due to their
      overexpression in breast and prostate cancers. Hence, these receptors can be
      potentially exploited for use in targeted drug delivery systems where dendrimer
      nanoparticles with multivalent ligand attachments can lead to greater specificity
      in cellular interactions. In this study, the single molecule force spectroscopy
      technique was used to assess the physical strength of multivalent interactions by
      employing a riboflavin (RF)-conjugated generation 5 PAMAM dendrimer G5(RF)n
      nanoparticle. By varying the average RF ligand valency (n = 0, 3, 5), the rupture
      force was measured between G5(RF)n and the riboflavin binding protein (RFBP). The
      rupture force increased when the valency of RF increased. We observed at the
      higher valency (n = 5) three binding events that increased in rupture force with
      increasing loading rate. Assuming a single energy barrier, the Bell-Evans model
      was used to determine the kinetic off-rate and barrier width for all binding
      interactions. The analysis of our results appears to indicate that multivalent
      interactions are resulting in changes to rupture force and kinetic off-rates. 

PMID- 25872804
TI  - Nucleic Acid Therapeutics Using Polyplexes: A Journey of 50 Years (and Beyond).

PMID- 25872805
TI  - The role of probiotics on each component of the metabolic syndrome and other
      cardiovascular risks.
AB  - INTRODUCTION: Probiotics are defined as live microorganisms that when
      administered in adequate amounts confer health benefits to the host. The
      consumption of probiotics has gained increasing recognition from the scientific
      community due to the promising effects on metabolic health through gut microbiota
      modulation. AREAS COVERED: This article presents a review of scientific studies
      investigating probiotic species and their effects on different risk factors of
      the metabolic syndrome (MetS). This article also presents a summary of the major
      mechanisms involved with gut microbiota and the components of the MetS and raises
      the key issues to be considered by scientists in search of probiotics species for
      treatment of patients suffering from this metabolic disorder. EXPERT OPINION:
      Probiotics may confer numerous health benefits to the host through positive gut
      microbiota modulation. The strain selection is the most important factor for
      determining health effects. Further studies may consider gut microbiota as a
      novel target for prevention and management of MetS components and other
      cardiovascular risks.

PMID- 25872807
TI  - We have more front line nurses, but at what cost?

PMID- 25872806
TI  - Relationships among ketosis, serum metabolites, body condition, and reproductive
      outcomes in dairy cows.
AB  - We determined the relationships among ketosis, serum metabolites, body condition,
      and reproductive disorders and performance in dairy cows. Blood samples from 213
      dairy cows were collected at 4 and 2 weeks prepartum, just after calving, and at
      1, 2, 4, 6, and 8 weeks postpartum to measure serum beta-hydroxybutyrate,
      nonesterified fatty acids (NEFAs), glucose, total cholesterol, urea nitrogen,
      aspartate aminotransferase, gamma-glutamyltransferase, and progesterone
      concentrations. Cows were grouped on the basis of the beta-hydroxybutyrate
      concentration at 1 and/or 2 weeks postpartum into two groups: the ketotic group
      (>=1200 MUmol/L, n = 59) and the nonketotic group (<1200 MUmol/L, n = 154). The
      body condition score (BCS) was assessed simultaneously with blood collection.
      Clinical endometritis was diagnosed by observation of vaginal discharges (>50%
      pus), and subclinical endometritis was diagnosed by evaluation of uterine
      cytology (>18% neutrophils) at 4 weeks postpartum. Ovarian cysts were diagnosed
      by ultrasonography, and resumption of postpartum cyclicity was evaluated by
      progesterone concentrations (>=1 ng/mL) at 4, 6, and 8 weeks postpartum. In the
      ketotic group, NEFA levels were higher (P <= 0.0005), whereas glucose (P < 0.05
      0.0005) and urea nitrogen levels (P < 0.05-0.01) were lower than those in the
      nonketotic group during the postpartum period. Aspartate aminotransferase levels
      were higher (P < 0.01) in the ketotic group than those in the nonketotic group at
      2 weeks postpartum. The BCS of the ketotic group was higher than the nonketotic
      group during the prepartum (P < 0.001) and postpartum (P < 0.05-0.001) periods.
      The probabilities of clinical endometritis (odds ratio = 2.55) and ovarian cysts
      (odds ratio = 2.80) were higher (P < 0.05) in the ketotic group than those in the
      nonketotic group. The hazards of resumption of postpartum cyclicity by 8 weeks
      postpartum (hazard ratio = 0.67) and pregnancy by 360 days postpartum (hazard
      ratio = 0.68) were lower (P < 0.05) in the ketotic group. In conclusion, a higher
      BCS during prepartum and postpartum period and increased NEFA and aspartate
      aminotransferase levels, along with decreased glucose and urea nitrogen levels
      during postpartum, were associated with ketosis, increased reproductive
      disorders, and decreased reproductive performance in dairy cows.

PMID- 25872808
TI  - Nightingale's table lamp set for auction.

PMID- 25872809
TI  - 'Spot test' survey reveals persistent concerns about low staffing levels.

PMID- 25872810
TI  - College vows to fight employers over pay refunds.

PMID- 25872811
TI  - Culture tool helps spot barriers to giving good care.

PMID- 25872812
TI  - Employers should offer mixed rotas, says Unison, amid 12-hour shifts row.

PMID- 25872813
TI  - Failed applications to nursing soar while staff face burnout, says RCN.

PMID- 25872814
TI  - 'Trixie' takes a trip to birthing unit.

PMID- 25872815
TI  - Pre-loading insulin syringe guidance updated by RCN.

PMID- 25872816
TI  - A safety alert for device connectors.

PMID- 25872818
TI  - Jobs fair travels to Glasgow.

PMID- 25872819
TI  - Patients 'confused' by dual charity and district nurse palliative care.

PMID- 25872820
TI  - NHS on the right road to achieving post-Francis change in its culture.

PMID- 25872826
TI  - Medicines in care homes.

PMID- 25872827
TI  - Delegation - a question of safety.
AB  - The NMC's revised Code strengthens considerably the regulator's standard on
      delegation. It underlines that registrants remain accountable for the tasks they
      delegate. They must ensure anyone to whom they delegate is competent, adequately
      supervised and properly supported.

PMID- 25872828
TI  - Raising the standard of brain cancer care.
AB  - Survival rates for people with brain cancer are poor, and some patients do not
      receive the specialist support they need. Nurse specialist Ingela Oberg calls for
      earlier diagnosis and improved access to nurse-led clinics and rehabilitation
      services.

PMID- 25872829
TI  - Best of both worlds at a hospital hospice.
AB  - An innovative nurse-led hospice has opened in an acute hospital in Lincolnshire.
      Staffed by the hospital's nurses, and supported by community palliative care
      specialists and GPs, the hospice is a model of integrated care. Patients benefit
      from the hospice ethos and easy access to the hospital.

PMID- 25872842
TI  - Why every vote must count if the government is to listen to nurses.

PMID- 25872843
TI  - Give maternity services robust racial equality protections.

PMID- 25872844
TI  - Training is needed but not at the cost of staff competition.

PMID- 25872845
TI  - What format should feedback for revalidation be taking?

PMID- 25872846
TI  - Compare like with like when analysing staffing levels.

PMID- 25872850
TI  - Medicines management.
AB  - All newly registered graduate nurses are required to have the appropriate
      knowledge and understanding to perform the skills required for patient care,
      specifically the competencies identified in the Nursing and Midwifery Council's
      essential skills clusters. This article focuses on the fifth essential skills
      cluster - medicines management. Nursing students should work to attain the
      knowledge and skills required for effective medicines management throughout their
      pre-registration education. The roles and responsibilities of the newly
      registered graduate nurse in the area of medicines management are discussed in
      this the final article of the essential skills cluster series.

PMID- 25872851
TI  - Systematic reviews.
AB  - Despite the increasing popularity of systematic reviews, there remains a need to
      ensure that they are conducted rigorously and provide an objective critical
      summary of research findings. The strength of a systematic review is its rigorous
      methodological approach to interrogating a body of literature. Both authors and
      readers should be familiar with the methodology used to conduct and evaluate
      systematic reviews. By way of introduction, this article explains and explores
      the steps that make up the systematic review process. 

PMID- 25872852
TI  - Chronic obstructive pulmonary disease part 1: smoking cessation.
AB  - Chronic obstructive pulmonary disease (COPD) is common in the UK and causes a
      significant burden to patients and the NHS. Healthcare provision for COPD is
      largely focused on biomedical treatment, yet research suggests the complexity of
      factors contributing to this disease requires a deeper understanding of the
      patient experience and a more holistic approach to the provision of care. Smoking
      cessation is the single most cost-effective and significant way to slow the
      disease progress and improve outcomes for patients. However, barriers to smoking
      cessation are higher in patients with COPD than in other groups, requiring
      different approaches. This is part one of a two-part article, which focuses on
      patients with COPD caused by smoking. The second part will focus on non
      pharmacological therapy. 

PMID- 25872853
TI  - Cardiovascular disease.

PMID- 25872854
TI  - Everyone's business.

PMID- 25872855
TI  - Happy to go the extra mile.

PMID- 25872857
TI  - Getting to grips with the bigger NHS picture.

PMID- 25872858
TI  - Application of optically active chiral bis(imidazolium) salts as potential
      receptors of chiral dicarboxylate salts of biological relevance.
AB  - A family of chiral bis(imidazolium) salts derived from natural amino acids has
      been synthesized by a simple synthetic approach and the corresponding
      bis(trifluoromethylsulfonyl)imide salts have been shown to be room temperature
      chiral ionic liquids (RTCILs). The structures and self-assembling properties of
      the resulting salts have been studied by (1)HNMR, ATR-FTIR, DSC, SEM and
      theoretical calculations. Moreover, these receptors have been applied to the
      enantiomeric recognition of dicarboxylic amino acids. The supramolecular
      complexes formed have been studied by (1)HNMR titration experiments, ATR-FTIR and
      DSC. 

PMID- 25872859
TI  - Are you dense?

PMID- 25872860
TI  - Seventy-Peak Kilovoltage High-Pitch Thoracic Aortic CT Angiography without ECG
      Gating: Evaluation of Image Quality and Radiation Dose.
AB  - RATIONALE AND OBJECTIVES: To assess the feasibility of 70-kVp high-pitch non-ECG
      gated thoracic aortic computed tomography angiography (CTA) with 40-mL contrast
      agent compared to 100-kVp standard-pitch CTA with 60-mL contrast agent. MATERIALS
      AND METHODS: Sixty-seven patients (51 men and 16 women; mean age, 55 +/- 14
      years) received non-ECG-gated aortic CTA at 70 kVp, high pitch of 3.4, and 40-mL
      contrast agent (group A, n = 31) or CTA at 100-kVp, pitch of 1.2, and 60-mL
      contrast agent (group B, n = 36). Iterative reconstruction was used in all
      patients. For image quality assessment, CTA images were evaluated on a three
      point scale and signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR)
      were calculated and compared. Furthermore, computed tomography (CT) dose index
      was recorded. RESULTS: Mean CT values and noise levels were higher in group A
      compared to group B (all P < .001), whereas SNR and CNR were lower than those in
      group B (all P < .001). Furthermore, the image quality of the aorta at the level
      of the diaphragm was lower in group A than that in group B (P < .05). However,
      image quality was graded as diagnostic in all patients, and motion artifacts of
      the aortic arch were significantly decreased in group A (P <.05). Interreader
      agreement was good or excellent for image quality assessment (k = 0.625-0.835).
      The 70-kVp CTA protocol, which allows dose reduction of 85%, was considered
      diagnostic in all instances by two readers. CONCLUSIONS: Our proposed thoracic
      aortic CTA protocol provides diagnostic information with substantial reduction of
      both radiation and contrast agent doses compared to standard-pitch CTA at 100
      kVp.

PMID- 25872861
TI  - Reducing the Radiation Dose for CT Colonography: Effect of Low Tube Voltage and
      Iterative Reconstruction.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study was to assess the effect of a
      low-tube-voltage technique and iterative reconstruction (IR) on the radiation
      dose and image quality of computed tomography colonography (CTC). MATERIALS AND
      METHODS: We studied 30 patients (14 women and 16 men; mean age, 64.5 +/- 13.1
      years; range, 39-90 years) with colorectal cancer referred for surgical
      treatment. All underwent CTC with fecal tagging under a standard 120-kVp protocol
      in the supine position and a 100-kVp protocol in the prone position. The 120-kVp
      images were reconstructed with filtered back projection (FBP). The 100-kVp images
      were postprocessed using FBP and a hybrid type of IR (adaptive iterative dose
      reduction 3D). The effective radiation dose (ED), image noise, and contrast-to
      noise ratio (CNR) were compared among the three protocols. The visual image
      quality was scored on a four-point scale. RESULTS: The mean ED was significantly
      lower under the 100-kVp protocol than the 120-kVp protocol, resulting in a 27%
      radiation dose decrease (3.5 +/- 2.0 vs 2.5 +/- 1.5 mSv; P < .01). Image noise
      decreased by 48%, and the mean attenuation of tagged fluid increased from 452 to
      558 HU on images acquired at 100 kVp with IR compared to that in the 120-kVp
      protocol; these differences were significant. The mean CNR was significantly
      higher under the 100 kVp with IR than the other two protocols. We found no
      significant differences in the visual scores for diagnostic utility between the
      100 kVp with IR and the 120 kVp with FBP protocol (P = .10). CONCLUSIONS: Low
      tube-voltage CTC reduced the radiation dose by approximately 27% while
      maintaining the image quality.

PMID- 25872862
TI  - Whole Breast Ultrasound: Comparison of the Visibility of Suspicious Lesions with
      Automated Breast Volumetric Scanning Versus Hand-Held Breast Ultrasound.
AB  - RATIONALE AND OBJECTIVES: To assess how well radiologists visualize relevant
      features of lesions seen with automated breast volumetric scanning (ABVS) in
      comparison to hand-held breast ultrasound in women going to breast biopsy.
      MATERIALS AND METHODS: Twenty-five subjects were recruited from women who were
      scheduled to undergo a breast biopsy for at least one Breast Imaging-Reporting
      and Data System four or five lesion identified in a diagnostic setting. In this
      institutional review board-approved study, the subjects underwent imaging of the
      breast(s) of concern using a dedicated system that allowed both hand-held breast
      ultrasound and ABVS. Five experienced breast radiologists reviewed the 30 lesions
      in 25 subjects in a reader study. Each reader was asked to specify the lesion
      type, size, imaging features, Breast Imaging-Reporting and Data System, and
      suspicion of malignancy and to compare the lesion characteristics of shape and
      margins between the two modalities. RESULTS: Seven (23.3%) masses were malignant
      and 23 (76.4%) were benign. Across all lesions regardless of size or final
      pathology, there was no significant difference in sensitivity or specificity (P >
      .15) between the two modalities. For malignant lesions, the reader visualization
      confidence scores between the two ultrasound modalities were not significantly
      different (P > .1). However, analysis for nonmalignant cases showed a
      statistically significant increase in reader visualization confidence in lesion
      shape and margins (P < .001). CONCLUSIONS: Radiologists showed increased
      confidence in visualization of benign masses and equal confidence in suspicious
      masses with ABVS imaging. This information could help decrease the need for
      additional hand-held imaging after automated whole breast ultrasound.

PMID- 25872863
TI  - PAHs content of sewage sludge in Europe and its use as soil fertilizer.
AB  - The European Commission has been planning limits for organic pollutants in sewage
      sludge for 14years; however no legislation has been implemented. This is mainly
      due to lack of data on sewage sludge contamination by organic pollutants, and
      possible negative effects to the environment. However, waste management has
      become an acute problem in many countries. Management options require extensive
      waste characterization, since many of them may contain compounds which could be
      harmful to the ecosystem, such as heavy metals, organic pollutants. The present
      study aims to show the true European position, regarding the polycyclic aromatic
      hydrocarbons (PAHs) content of sewage sludge, by comparing the Italian PAHs
      content with European Union countries, and at assessing the suitability of sewage
      sludge as soil fertilizer. The FOCUS Pearl model was used to estimate the
      concentration of benzo [a] pyrene (B(a)Pyr), the most toxic PAH in soil, and its
      exposure to organisms was then evaluated. The simulated B(a)Pyr and PAHs,
      expressed as B(a)Pyr, concentrations in soil were much lower than the B(a)Pyr's
      most conservative lowest observable effect concentration (LOEC) for soil
      organisms. Furthermore, the results obtained indicate that it is more appropriate
      to apply 5tha(-1) sewage sludge annually than 15tha(-1) triennially. Results
      suggest, the EU maximum recommended limit of 6mgkg(-)(1) PAHs in sewage sludge,
      should be conservative enough to avoid groundwater contamination and negative
      effects on soil organisms. 

PMID- 25872864
TI  - Feasibility study of biodiesel production using lipids of Hermetia illucens larva
      fed with organic waste.
AB  - Hermetia illucens larvae by nature are a decomposer which fed on organic wastes.
      This study explores the potential of producing biodiesel using lipids from H.
      illucens larvae. Three types of organic wastes (sewage sludge, fruit waste and
      palm decanter cake from oil palm mill) were selected based on considerable
      generation and disposal concern in the area of study as well as lack of
      investigations as feed for Hermetia illucens larvae in current literatures.
      Growth rate of the larvae was determined with studying the changes in the biomass
      per day. H. illucens larvae fed with fruit waste and palm decanter cake have
      shown growth rates of 0.52+/-0.02 and 0.23+/-0.09 g d(-1), respectively. No
      positive sign of growth were observed in the larvae fed with treated sewage
      sludge (-0.04+/-0.01 g d(-1)). Biodiesel as fatty acid methyl ester (FAME) was
      synthesized by transesterification of the larvae lipid using sulphuric acid as
      catalyst in methanol. FAME produced was ascertained using ATR-FTIR spectroscopy
      and GC-MS. The main compositions of fatty acid were found to be C12:0, C16:0 and
      C18:1n9c. Fatty acid composition of C12:0 fed with fruit waste, sewage sludge and
      palm decanter was found to be most abundant in the larvae lipid. The amount of
      C12:0 obtained was 76.13%, 58.31% and 48.06%, respectively. In addition, fatty
      acid of C16:0 was attained at 16.48% and 25.48% fed with sewage sludge and palm
      decanter, respectively. Based on the findings, FAME derived from larvae lipids is
      feasible to be used for biodiesel production.

PMID- 25872865
TI  - Nitroarene reduction: a trusted model reaction to test nanoparticle catalysts.
AB  - Nitrophenol reduction to aminophenol with a reducing agent is conveniently
      carried out in aqueous medium mainly with a metal or metal oxide catalyst. This
      reduction is presently considered as a benchmark reaction to test a catalyst
      nanoparticle. Thousands of original reports have enriched this field of
      nanoparticle catalyzed reaction. Synthesis of different metal and metal oxide
      nanoparticles and their composites along with their role as catalysts for
      nitrophenol reduction with varying reducing agents have been elucidated here. The
      progress of the reaction is conveniently monitored by UV-visible
      spectrophotometry and hence it becomes a universally accepted model reaction. In
      this review we have discussed the reaction kinetics considering its elegance and
      importance enlightening the long known Langmuir-Hinshelwood mechanism and Eley
      Rideal mechanism at length, along with a few other mechanisms recently reported.
      A brief description of the synthetic procedures of various nanoparticles and
      their respective catalytic behaviour towards nitroarene reduction has also been
      accounted here. 

PMID- 25872866
TI  - Lower weight loss expectations and healthier eating attitudes in older overweight
      and obese women attempting weight loss.
AB  - Weight loss outcomes in overweight and obese individuals may be influenced by
      individual weight loss expectations (WLEs). Research on these phenomena in older
      women is lacking. This cross-sectional study compared groups of younger and older
      women on their WLEs and related attitudes (body dissatisfaction and disordered
      eating). Twenty-six younger (18-38 years) and 33 older (60-78 years) overweight
      and obese women were recruited from a weight loss clinic, prior to treatment.
      Disordered eating attitudes and body dissatisfaction were assessed using
      validated questionnaires and a pictorial figure-choice scale. Participants
      reported 10 WLEs categorized according to personal, lifestyle and social factors.
      Overall, women with a higher body mass index had greater WLEs. Older women
      reported lower WLEs than younger women (-14.5 kg vs. -22.4 kg) in all categories
      except past weight. Older women perceived that career success would necessitate
      the greatest level of weight loss (-18.5 kg), whereas younger women derived their
      greatest WLEs from mass media (-28.5 kg). Both older and younger groups perceived
      that their families would be supportive of the smallest amount of weight loss (
      8.4 and -17.6 kg, respectively). The groups did not differ on body
      dissatisfaction, but younger women's disordered eating attitudes were
      significantly higher (p < .001). Older overweight and obese women have lower WLEs
      than younger women but experience similar levels of body dissatisfaction and
      healthier eating attitudes. The attitudinal constructs underlying these
      differences may be useful in clinical practice to tailor age-specific weight loss
      interventions.

PMID- 25872867
TI  - Ultrafine sodium titanate nanowires with extraordinary Sr ion-exchange
      properties.
AB  - Ultrafine sodium titanate nanowires are produced from TiAl alloy precursors via a
      nonthermal process where Al leaching and Ti oxidation occur simultaneously in an
      alkaline medium. The obtained nanowires demonstrate a layered crystal structure
      with a diameter of a few nanometers and exhibit remarkable Sr ion-exchange
      properties. 

PMID- 25872868
TI  - Amino acid uptake in erythropoiesis.
AB  - Erythroblasts produce huge amounts of hemoglobin, for which they must incorporate
      vast stores of iron and amino acids. In the 14 April issue of Science Signaling,
      Chung et al. describe the complex mechanism linking neutral amino acid uptake to
      hemoglobin production in these hungry cells. 

PMID- 25872871
TI  - Constitutive production of c-di-GMP is associated with mutations in a variant of
      Pseudomonas aeruginosa with altered membrane composition.
AB  - Most bacteria can form multicellular communities called biofilms on biotic and
      abiotic surfaces. This multicellular response to surface contact correlates with
      an increased resistance to various adverse environmental conditions, including
      those encountered during infections of the human host and exposure to
      antimicrobial compounds. Biofilm formation occurs when freely swimming
      (planktonic) cells encounter a surface, which stimulates the chemosensory-like,
      surface-sensing system Wsp and leads to generation of the intracellular second
      messenger 3',5'-cyclic-di-guanosine monophosphate (c-di-GMP). We identified
      adaptive mutations in a clinical small colony variant (SCV) of Pseudomonas
      aeruginosa and correlated their presence with self-aggregating growth behavior
      and an enhanced capacity to form biofilms. We present evidence that a point
      mutation in the 5' untranslated region of the accBC gene cluster, which encodes
      components of an enzyme responsible for fatty acid biosynthesis, was responsible
      for a stabilized mRNA structure that resulted in reduced translational efficiency
      and an increase in the proportion of short-chain fatty acids in the plasma
      membrane. We propose a model in which these changes in P. aeruginosa serve as a
      signal for the Wsp system to constitutively produce increased amounts of c-di-GMP
      and thus play a role in the regulation of adhesion-stimulated bacterial
      responses. 

PMID- 25872870
TI  - Casein kinase 2 (CK2) phosphorylates the deubiquitylase OTUB1 at Ser16 to trigger
      its nuclear localization.
AB  - The deubiquitylating enzyme OTUB1 is present in all tissues and targets many
      substrates, in both the cytosol and nucleus. We found that casein kinase 2 (CK2)
      phosphorylated OTUB1 at Ser(16) to promote its nuclear accumulation in cells.
      Pharmacological inhibition or genetic ablation of CK2 blocked the phosphorylation
      of OTUB1 at Ser(16), causing its nuclear exclusion in various cell types. Whereas
      we detected unphosphorylated OTUB1 mainly in the cytosol, we detected Ser(16)
      phosphorylated OTUB1 only in the nucleus. In vitro, Ser(16)-phosphorylated OTUB1
      and nonphosphorylated OTUB1 exhibited similar catalytic activity, bound K63
      linked ubiquitin chains, and interacted with the E2 enzyme UBE2N. CK2-mediated
      phosphorylation and subsequent nuclear localization of OTUB1 promoted the
      formation of 53BP1 (p53-binding protein 1) DNA repair foci in the nucleus of
      osteosarcoma cells exposed to ionizing radiation. Our findings indicate that the
      activity of CK2 is necessary for the nuclear translocation and subsequent
      function of OTUB1 in DNA damage repair. 

PMID- 25872872
TI  - Exploiting anthracene photodimerization within peptides: light induced sequence
      selective DNA binding.
AB  - The unprecedented use of anthracene photodimerization within a protein or peptide
      system is explored through its incorporation into a DNA-binding peptide, derived
      from the GCN4 transcription factor. This study demonstrates an effective and
      dynamic interplay between a photoreaction and a peptide-DNA assembly, with each
      process able to exert control over the other. 

PMID- 25872869
TI  - The mTORC1/4E-BP pathway coordinates hemoglobin production with L-leucine
      availability.
AB  - In multicellular organisms, the mechanisms by which diverse cell types acquire
      distinct amino acids and how cellular function adapts to their availability are
      fundamental questions in biology. We found that increased neutral essential amino
      acid (NEAA) uptake was a critical component of erythropoiesis. As red blood cells
      matured, expression of the amino acid transporter gene Lat3 increased, which
      increased NEAA import. Inadequate NEAA uptake by pharmacologic inhibition or RNAi
      mediated knockdown of LAT3 triggered a specific reduction in hemoglobin
      production in zebrafish embryos and murine erythroid cells through the mTORC1
      (mammalian target of rapamycin complex 1)/4E-BP (eukaryotic translation
      initiation factor 4E-binding protein) pathway. CRISPR-mediated deletion of
      members of the 4E-BP family in murine erythroid cells rendered them resistant to
      mTORC1 and LAT3 inhibition and restored hemoglobin production. These results
      identify a developmental role for LAT3 in red blood cells and demonstrate that
      mTORC1 serves as a homeostatic sensor that couples hemoglobin production at the
      translational level to sufficient uptake of NEAAs, particularly L-leucine.

PMID- 25872873
TI  - Recurrent Aphthous Stomatitis in Childhood and Adolescence: A Single-Center
      Experience.
AB  - BACKGROUND: Recurrent aphthous stomatitis (RAS) is a common oral ulcerative
      condition in children. The objective was to describe the clinical features of RAS
      in children with accompanying clinical and laboratory findings. METHODS: The
      study included 120 patients younger than 18 years of age (mean age 9.6 +/- 4.3
      years) with three or more oral aphthous ulcers per year between August 2008 and
      February 2014. Demographic characteristics of the patients, clinical features of
      the ulcers, and associated clinical and laboratory findings were evaluated.
      RESULTS: The mean number of aphthae per year was 12.8 +/- 8.5 and the mean
      duration of the disease was 3.6 +/- 2.9 years. Minor aphthae were the most common
      type (87%), papulopustules were the most common accompanying cutaneous lesions
      (13.3%), and family history of RAS was the most common associated factor (35.8%).
      Genital scarring (p = 0.04) and pathergy (p = 0.01) were significantly more
      common in the adolescent group. Pathergy was significantly related to genital
      scarring (p = 0.04) and Behcet's disease (p = 0.02). There was no association
      between the number of aphthae per year and the duration of the disease and
      hematologic and immunologic abnormalities. CONCLUSION: Our study is consistent
      with previous reports in terms of clinical features of aphthous ulcers, related
      diseases, and family history of RAS, but no associated laboratory abnormalities
      were noted.

PMID- 25872874
TI  - Real-time dielectrophoretic signaling and image quantification methods for
      evaluating electrokinetic properties of nanoparticles.
AB  - Real-time image signaling and quantification methods are described that allow
      easy-to-use, fast extraction of the electrical properties of nanoparticles.
      Positive dielectrophoretic (pDEP) collection rate analysis enables the dielectric
      properties of very small samples of nanoparticles to be accurately quantified.
      Advancing earlier work involving dual-cycle pulsed pDEP collection experiments,
      we report the development of a statistical image quantification method that
      significantly advances the evaluation of nanoparticle dielectric properties.
      Compared with traditional methods that require information about the geometry of
      the electrode array to be entered for semiautomated quantification , the new
      statistical approach described does not require a priori knowledge of device
      geometry. The efficacy of the statistical method is experimentally demonstrated
      using 200 nm diameter latex nanospheres, suspended in low conductivity medium,
      that are attracted by pDEP onto planar castellated electrode arrays with 5-micron
      sized features. The method is shown to yield estimates for the nanoparticle
      conductivity and surface conductance, sigmap=25.8 mS/m and KS=1.29 nS, that
      concur closely with those obtained using traditional geometric methods previously
      reported . Consequently, the statistical method is accurate, fast, robust,
      supervisor-free, and useful for determining nanoparticle electrokinetic
      parameters. 

PMID- 25872875
TI  - Relationship Between Prior PCI and Subsequent CABG.

PMID- 25872876
TI  - Troglitazone suppresses glutamine metabolism through a PPAR-independent
      mechanism.
AB  - Enhanced glutamine metabolism is required for tumor cell growth and survival,
      which suggests that agents targeting glutaminolysis may have utility within anti
      cancer therapies. Troglitazone, a PPARgamma agonist, exhibits significant anti
      tumor activity and can alter glutamine metabolism in multiple cell types.
      Therefore, we examined whether troglitazone would disrupt glutamine metabolism in
      tumor cells and whether its action was reliant on PPARgamma activity. We found
      that troglitazone treatment suppressed glutamine uptake and the expression of the
      glutamine transporter, ASCT2, and glutaminase. In addition, troglitazone reduced
      13C-glutamine incorporation into the TCA cycle, decreased [ATP], and resulted in
      an increase in reactive oxygen species (ROS). Further, troglitazone treatment
      decreased tumor cell growth, which was partially rescued with the addition of the
      TCA-intermediate, alpha-ketoglutarate, or the antioxidant N-acetylcysteine.
      Importantly, troglitazone's effects on glutamine uptake or viable cell number
      were found to be PPARgamma-independent. In contrast, troglitazone caused a
      decrease in c-Myc levels, while the proteasomal inhibitor, MG132, rescued c-Myc,
      ASCT2 and GLS1 expression, as well as glutamine uptake and cell number. Lastly,
      combinatorial treatment of troglitazone and metformin resulted in a synergistic
      decrease in cell number. Therefore, characterizing new anti-tumor properties of
      previously approved FDA therapies supports the potential for repurposing of these
      agents. 

PMID- 25872877
TI  - Cathepsin S: therapeutic, diagnostic, and prognostic potential.
AB  - Cathepsin S is a member of the cysteine cathepsin protease family. It is a
      lysosomal protease which can promote degradation of damaged or unwanted proteins
      in the endo-lysosomal pathway. Additionally, it has more specific roles such as
      MHC class II antigen presentation, where it is important in the degradation of
      the invariant chain. Unsurprisingly, mis-regulation has implicated cathepsin S in
      a variety of pathological processes including arthritis, cancer, and
      cardiovascular disease, where it becomes secreted and can act on extracellular
      substrates. In comparison to many other cysteine cathepsin family members,
      cathepsin S has uniquely restricted tissue expression and is more stable at a
      neutral pH, which supports its involvement and importance in localised disease
      microenvironments. In this review, we examine the known involvement of cathepsin
      S in disease, particularly with respect to recent work indicating its role in
      mediating pain, diabetes, and cystic fibrosis. We provide an overview of current
      literature with regards cathepsin S as a therapeutic target, as well as its role
      and potential as a predictive diagnostic and/or prognostic marker in these
      diseases. 

PMID- 25872879
TI  - A perspective on complementary/alternative medicine use among survivors of
      hematopoietic stem cell transplant: Benefits and uncertainties.
AB  - The widespread use of complementary and alternative medicine (CAM) in cancer
      survivors is well known despite a paucity of scientific evidence to support its
      use. The number of survivors of hematopoietic stem cell transplant (HCT) is
      growing rapidly and HCT clinicians are aware that many of their patients use CAM
      therapies consistently. However, due to a paucity of data regarding the benefits
      and harms of CAM therapies in these survivors, clinicians are reluctant to
      provide specific recommendations for or against particular CAM therapies. A
      systematic literature review was conducted with a search using PubMed, the
      Cochrane Database of Systematic Reviews, and Ovid online for each CAM therapy as
      defined by the National Center of Complementary and Alternative Medicine. The
      search generated 462 references, of which 26 articles were deemed to be relevant
      for the review. Due to extensive heterogeneity in data and limited randomized
      trials, a meta-analysis could not be performed but a comprehensive systematic
      review was conducted with specified outcomes for each CAM therapy. In randomized
      controlled trials, certain mind and body interventions such as relaxation were
      observed to be effective in alleviating psychological symptoms in patients
      undergoing HCT, whereas the majority of the other CAM treatments were found to
      have mixed results. CAM use is an understudied area in HCT survivorship and
      clinicians should convey the benefits and uncertainties concerning the role of
      CAM therapies to their patients.

PMID- 25872878
TI  - The abscopal effect of local radiotherapy: using immunotherapy to make a rare
      event clinically relevant.
AB  - BACKGROUND: Recently, immunologic responses to localized irradiation are proposed
      as mediator of systemic effects after localized radiotherapy (called the abscopal
      effect). Here, we give an overview of both preclinical and clinical data about
      the abscopal effect in particular and link them with the immunogenic properties
      of radiotherapy. METHODS: We searched Medline and Embase with the search term
      "abscopal", "(non-targeted irradiation) OR (non-targeted radiotherapy)" and
      "distant bystander" from 1960 until July, 2014. Only papers that cover
      radiotherapy in an oncological setting were selected and only if no concurrent
      cytotoxic treatment was given. Targeted immune therapy was allowed. RESULTS:
      Twenty-three case reports, one retrospective study and 13 preclinical papers were
      selected. Eleven preclinical papers used a combination of immune modification and
      radiotherapy to achieve abscopal effects. Patient age range (28-83years) and
      radiation dose (median total dose 32Gy) varied. Fractionation size ranged from
      1.2Gy to 26Gy. Time to documented abscopal response ranged between less than one
      and 24months, with a median reported time of 5months. Once an abscopal response
      was achieved, a median time of 13months went by before disease progression
      occurred or the reported follow-up ended (range 3-39months). CONCLUSION:
      Preclinical data points heavily toward a strong synergy between radiotherapy and
      immune treatments. Recent case reports already illustrate that such a systemic
      effect of radiotherapy is possible when enhanced by targeted immune treatments.
      However, several issues concerning dosage, timing, patient selection and toxicity
      need to be resolved before the abscopal effect can become clinically relevant.

PMID- 25872880
TI  - Exact and asymptotic inference in clinical trials with small event rates under
      inverse sampling.
AB  - In this paper, we discuss statistical inference for a 2 * 2 table under inverse
      sampling, where the total number of cases is fixed by design. We demonstrate that
      the exact unconditional distributions of some relevant statistics differ from the
      distributions under conventional sampling, where the sample size is fixed by
      design. This permits us to define a simple unconditional alternative to Fisher's
      exact test. We provide an asymptotic argument including simulations to
      demonstrate that there is little power loss associated with the alternative test
      when the expected event rates are very small. We then apply the method to design
      a clinical trial in cataract surgery, where a rare side effect occurs in one in
      1000 patients. The objective of the trial is to demonstrate that adjuvant
      treatment with an antibiotic will reduce this risk to one in 2000. We use an
      inverse sampling design and demonstrate how to set this up in a sequential
      manner. Particularly simple stopping rules can be defined when using the
      unconditional alternative to Fisher's exact test.

PMID- 25872881
TI  - Porous cobalt-based thin film as a bifunctional catalyst for hydrogen generation
      and oxygen generation.
AB  - A mixed-phased Co-based catalyst composed of Co phosphide and Co phosphate is
      successfully fabricated for bifunctional water electrolysis. The highly porous
      morphology in this anodized film enables efficient catalytic activity toward
      water splitting in an extremely low loading mass. The mixed phases in the porous
      film afford an ability to generate both H2 and O2 in a single electrolyzer. 

PMID- 25872882
TI  - 2ME2 increase radiation-induced apoptosis of keloid fibroblasts by targeting HIF
      1alpha in vitro.
AB  - BACKGROUND: Radiation therapy is considered to be a treatment for keloid
      scarring; however, radioresistance has been shown to be a serious impediment to
      treatment efficacy. There is therefore a need for the discovery of novel critical
      molecular targets whose inhibition might enhance the radiotherapeutic response.
      An elevated level of hypoxia inducible factor (HIF)-1alpha expression after
      radiation therapy in keloid fibroblasts has been demonstrated in our recent
      experiments. Therefore, we suggested there was a possible close relationship
      between HIF-1alpha and keloid radioresistance. The current study aimed to
      investigate whether target HIF-1alpha may enhance the radiotherapeutic efficacy
      of keloids. METHODS: 2-methoxyestradiol (2ME2) was applied to inhibit HIF-1alpha
      expression, and the treatment results were assessed by cell proliferation,
      apoptosis and radiosensitivity. A lentivirus-mediated small interfering RNA
      (siRNA) transduction method was used to block the expression of HIF-1alpha gene.
      RESULTS: Both mRNA and protein levels can be effectively inhibited after the
      knockdown of HIF-1alpha, leading to a significant increase of radiation-induced
      apoptosis in keloid fibroblasts. Our experiment also demonstrated that 2ME2 could
      effectively inhibit the protein expression of HIF-1alpha, which significantly
      increased the late stage of radiation-induced apoptosis of keloid fibroblasts.
      CONCLUSIONS: The present study indicates that HIF-1alpha might serve as a
      therapeutic target for keloids. Furthermore, suppression of HIF-1alpha by 2ME2
      may be a promising therapeutic adjuvant in radiation therapy for keloids.

PMID- 25872883
TI  - (Hollow Au-Ag nanoparticles)-TiO2 composites for improved photocatalytic activity
      prepared from block copolymer-stabilized bimetallic nanoparticles.
AB  - Composite nanoparticles (NPs) containing a TiO2 outer shell and an inner core of
      hollow AuAg NPs (H-AuAg-NPs) were prepared using hollow AuAg NPs with block
      copolymer shells as templates, and their photocatalytic activities were
      investigated by the decomposition of methylene blue dye under UV irradiation. It
      was found that the H-AuAg-NP-TiO2 composite NPs showed higher photocatalytic
      activity than AuAg alloy-TiO2 composite NPs, Ag/TiO2 NPs and TiO2 NPs. In
      addition, the photocatalytic activity first increases with increasing the TiO2
      content from 2.5% to 5.0% and then decreases with a further increase in TiO2
      content from 10.0% to 15.0%. 

PMID- 25872884
TI  - Reflecting on 'Supporting health systems in Europe: added value of EU actions?'.

PMID- 25872885
TI  - Percutaneous cholecystostomy in acute cholecystitis; a retrospective analysis of
      a large series of 104 patients.
AB  - BACKGROUND: The purpose of this study was to evaluate the clinical course and
      possible benefit of a percutaneous cholecystostomy in patients with acute
      cholecystitis. METHODS: Retrospective study of 104 patients with severe
      cholecystitis or cholecystitis not responding to antibiotic therapy treated with
      percutaneous drainage of the gall bladder (PC) during the period 2007 - 2013.
      Primary outcome was relief of cholecystitis, complications following the
      procedure and need for later cholecystectomy. RESULTS: There were 57 men and 47
      women with a median age of 73,5 years (range 22 - 96). 43% of the patients were
      ASA III or IV and 91% had cholecystitis Grade 2 or 3. About 60% of the patients
      had severe comorbidity (cardiovascular disease or active cancer). Drain insertion
      was successful in all but one patient and complications were mild, apart from two
      patients that needed percutaneous drainage of intraabdominal fluid collection due
      to bile leakage. The drain was left in place for 1 - 75 days (median 6,5). When
      evaluated clinically and by blood tests (CRP and white blood cell counts) we
      found resolution of symptoms in 101 patients (97,2%), whereas 2 patients had no
      obvious effect of drainage. Four patients died within 30 days, no deaths were
      related to the drainage procedure. Follow-up after drainage was median 12 months
      (range 0 - 78). During that time cholecystectomy was performed in 30 patients and
      24 patients had died. Following cholecystectomy, two had died, both from cancer
      and more than one year after the operation. CONCLUSION: Patients with acute
      cholecystitis were promptly relieved from their symptoms following PC. There were
      only minor complications following the procedure and only about 30% of the
      patients had a later cholecystectomy.

PMID- 25872886
TI  - Clinical presentations of 23 half-siblings from a mosaic neurofibromatosis type 1
      sperm donor.
AB  - The Danish sperm donor number 7042 has fathered several offspring with
      neurofibromatosis type 1 (NF1) worldwide. NF1 is caused by loss-of-function
      mutations in the NF1 gene and more than 1000 NF1 mutations are identified.
      Analysis of the donor sperm demonstrated gonosomal mosaicism with an intragenic
      deletion involving exons 15-29 in the NF1 gene. At the two Danish reference
      centres for NF1 patients, we evaluated 23 half-siblings from the donor. Nine were
      diagnosed with NF1. The severity grade of NF1 progressed from minimal to
      mild/moderate within 3 years of follow-up. The NF1 phenotype shows great
      variability in intra- and inter-family expressivity and to date only two NF1
      genotype-phenotype correlations have been established. This rare possibility of a
      long-term follow-up of a cohort of half-siblings with NF1 makes further studies
      including phenotypic variability and search for modifier genes possible. To
      achieve this goal, we have initiated The International Donor 7042 NF1 Offspring
      Registry. Research facilitated via this registry may reveal important new
      knowledge of clinical characteristics and prognostics for the specific NF1
      genotype and thereby contribute to future individualised targeted clinical follow
      up and treatment.

PMID- 25872887
TI  - Nerve-sparing radical hysterectomy: time for a new standard of care for cervical
      cancer?

PMID- 25872888
TI  - Ovarian cancer risk reduction through opportunistic salpingectomy.

PMID- 25872889
TI  - FIGO's staging classification for cancer of the ovary, fallopian tube, and
      peritoneum: abridged republication.

PMID- 25872890
TI  - Efficacy and oncologic safety of nerve-sparing radical hysterectomy for cervical
      cancer: a randomized controlled trial.
AB  - OBJECTIVE: A prospective, randomized controlled trial was conducted to evaluate
      the efficacy of nerve-sparing radical hysterectomy (NSRH) in preserving bladder
      function and its oncologic safety in the treatment of cervical cancer. METHODS:
      From March 2003 to November 2005, 92 patients with cervical cancer stage IA2 to
      IIA were randomly assigned for surgical treatment with conventional radical
      hysterectomy (CRH) or NSRH, and 86 patients finally included in the analysis.
      Adequacy of nerve sparing, radicality, bladder function, and oncologic safety
      were assessed by quantifying the nerve fibers in the paracervix, measuring the
      extent of paracervix and harvested lymph nodes (LNs), urodynamic study (UDS) with
      International Prostate Symptom Score (IPSS), and 10-year disease-free survival
      (DFS), respectively. RESULTS: There were no differences in clinicopathologic
      characteristics between two groups. The median number of nerve fiber was 12
      (range, 6 to 21) and 30 (range, 17 to 45) in the NSRH and CRH, respectively
      (p<0.001). The extent of resected paracervix and number of LNs were not different
      between the two groups. Volume of residual urine and bladder compliance were
      significantly deteriorated at 12 months after CRH. On the contrary, all
      parameters of UDS were recovered no later than 3 months after NSRH. Evaluation of
      the IPSS showed that the frequency of long-term urinary symptom was higher in CRH
      than in the NSRH group. The median duration before the postvoid residual urine
      volume became less than 50 mL was 11 days (range, 7 to 26 days) in NSRH group and
      was 18 days (range, 10 to 85 days) in CRH group (p<0.001). No significant
      difference was observed in the 10-year DFS between two groups. CONCLUSION: NSRH
      appears to be effective in preserving bladder function without sacrificing
      oncologic safety.

PMID- 25872891
TI  - Conventional versus nerve-sparing radical surgery for cervical cancer: a meta
      analysis.
AB  - OBJECTIVE: Although nerve-sparing radical surgery (NSRS) is an emerging technique
      for reducing surgery-related dysfunctions, its efficacy is controversial in
      patients with cervical cancer. Thus, we performed a meta-analysis to compare
      clinical outcomes, and urinary, anorectal, and sexual dysfunctions between
      conventional radical surgery (CRS) and NSRS. METHODS: After searching PubMed,
      Embase, and the Cochrane Library, two randomized controlled trials, seven
      prospective and eleven retrospective cohort studies were included with 2,253
      patients from January 2000 to February 2014. We performed crude analyses and then
      conducted subgroup analyses according to study design, quality of study, surgical
      approach, radicality, and adjustment for potential confounding factors. RESULTS:
      Crude analyses showed decreases in blood loss, hospital stay, frequency of
      intraoperative complications, length of the resected vagina, duration of
      postoperative catheterization (DPC), urinary frequency, and abnormal sensation in
      NSRS, whereas there were no significant differences in other clinical parameters
      and dysfunctions between CRS and NSRS. In subgroup analyses, operative time was
      longer (standardized difference in means, 0.948; 95% confidence interval [CI],
      0.642 to 1.253), while intraoperative complications were less common (odds ratio,
      0.147; 95% CI, 0.035 to 0.621) in NSRS. Furthermore, subgroup analyses showed
      that DPC was shorter, urinary incontinence or frequency, and constipation were
      less frequent in NSRS without adverse effects on survival and sexual functions.
      CONCLUSION: NSRS may not affect prognosis and sexual dysfunctions in patients
      with cervical cancer, whereas it may decrease intraoperative complications, and
      urinary and anorectal dysfunctions despite long operative time and short length
      of the resected vagina when compared with CRS.

PMID- 25872892
TI  - Low initial human papillomavirus viral load may indicate worse prognosis in
      patients with cervical carcinoma treated with surgery.
AB  - OBJECTIVE: To evaluate the prognostic implication of human papillomavirus (HPV)
      viral load in cervical cancer patients who underwent radical hysterectomy.
      METHODS: We conducted a retrospective review of patients with stage IA2 through
      stage IIIA cervical carcinoma who underwent radical hysterectomy at Sun Yat-sen
      University Cancer Center between January 2005 and December 2009. Patients who had
      undergone preoperative hybrid capture 2 testing to detect HPV DNA were included.
      A total of 346 patients positive for HPV DNA were enrolled and stratified into
      two groups according to the median HPV viral load. RESULTS: HPV viral load was
      significantly correlated with lymphovascular space invasion (p=0.026) and deep
      stromal invasion (p=0.024). However, other factors, such as age, stage,
      histologic grade, histologic type, lymph node metastasis, and tumor size, were
      not significantly associated with viral load. Low HPV viral load was correlated
      with poor disease-free survival in univariate analysis (p=0.037) and multivariate
      analysis (p=0.027). There was no significant difference in overall survival with
      regard to initial HPV viral load. CONCLUSION: Low initial HPV viral load may be a
      poor prognostic factor for cervical cancer patients who have undergone radical
      hysterectomy.

PMID- 25872893
TI  - Implications of a two-step procedure in surgical management of patients with
      early-stage endometrioid endometrial cancer.
AB  - OBJECTIVE: Since European Society for Medical Oncology (ESMO) recommendations and
      French guidelines, pelvic lymphadenectomy should not be systematically performed
      for women with early-stage endometrioid endometrial cancer (EEC) preoperatively
      assessed at presumed low- or intermediate-risk. The aim of our study was to
      evaluate the change of our surgical practices after ESMO recommendations, and to
      evaluate the rate and morbidity of second surgical procedure in case of
      understaging after the first surgery. METHODS: This retrospective single-center
      study included women with EEC preoperatively assessed at presumed low- or
      intermediate-risk who had surgery between 2006 and 2013. Two periods were defined
      the times before and after ESMO recommendations. Demographics characteristics,
      surgical management, operative morbidity, and rate of understaging were compared.
      The rate of second surgical procedure required for lymph node resection during
      the second period and its morbidity were also studied. RESULTS: Sixty-one and
      sixty-two patients were operated for EEC preoperatively assessed at presumed low
      or intermediate-risk before and after ESMO recommendations, respectively.
      Although immediate pelvic lymphadenectomy was performed more frequently during
      the first period than the second period (88.5% vs. 19.4%; p<0.001), the rate of
      postoperative risk-elevating or upstaging were comparable between the two periods
      (31.1% vs. 27.4%; p=0.71). Among the patients requiring second surgical procedure
      during the second period (21.0%), 30.8% did not undergo the second surgery due to
      their comorbidity or old age. For the patients who underwent second surgical
      procedure, mean operative time of the second procedure was 246.1+/-117.8 minutes.
      Third operation was required in 33.3% of them because of postoperative
      complications. CONCLUSION: Since ESMO recommendations, second surgical procedure
      for lymph node resection is often required for women with EEC presumed at low- or
      intermediate-risk. This reoperation is not always performed due to
      age/comorbidity of the patients, and presents a significant morbidity.

PMID- 25872894
TI  - Physical activity for an ethnically diverse sample of endometrial cancer
      survivors: a needs assessment and pilot intervention.
AB  - OBJECTIVE: To determine the physical activity (PA) behavior, needs and
      preferences for underserved, ethnically diverse women with a history of
      endometrial cancer (EC). METHODS: Women with a history of EC (41 non-Hispanic
      black, 40 non-Hispanic white, and 18 Hispanic) completed a needs assessment
      during their regular follow-up appointments at Montefiore Medical Center in
      Bronx, NY, USA. An 8-week pilot PA intervention based on the results of the needs
      assessment was conducted with 5 EC survivors. RESULTS: Mean body mass index (BMI)
      among the 99 respondents was 34.1+/-7.6 kg/m2, and 66% did not exercise
      regularly. Self-described weight status was significantly lower than actual BMI
      category (p<0.001). Of the 86% who were interested in joining an exercise
      program, 95% were willing to attend at least once weekly. The primary motivations
      were improving health, losing weight, and feeling better physically. Despite the
      high interest in participation, volunteer rate was very low (8%). However,
      adherence to the 8-week pilot PA intervention was high (83%), and there were no
      adverse events. Body weight decreased in all pilot participants. CONCLUSION:
      These data show that ethnically diverse EC survivors have a great need for, and
      are highly interested in, PA interventions. However, greater care needs to be
      taken to assess and identify barriers to increase participation in such programs.

PMID- 25872895
TI  - Surgical technique of en bloc pelvic resection for advanced ovarian cancer.
AB  - OBJECTIVE: The aim of this paper was to describe the operative details for en
      bloc removal of the adnexal tumor, uterus, pelvic peritoneum, and rectosigmoid
      colon with colorectal anastomosis in advanced epithelial ovarian cancer patients
      with widespread pelvic involvement. METHODS: The patient presented with good
      performance status and huge pelvic tumor extensively infiltrating into adjacent
      pelvic organs and obliterating the cul-de-sac. The patient underwent en bloc
      pelvic resection as primary cytoreductive surgery. En bloc pelvic resection
      procedure is initiated by carrying a circumscribing peritoneal incision to
      include all pan-pelvic disease within this incision. After retroperitoneal pelvic
      dissection, the round ligaments and infundibulopelvic ligaments are divided. The
      ureters are dissected and mobilized from the peritoneum. After dissecting off the
      anterior pelvic peritoneum overlying the bladder with its tumor nodules, the
      bladder is mobilized caudally and the vesicovaginal space is developed. The
      uterine vessels are divided at the level of the ureters, and the paracervical
      tissues (or parametria) are divided. The proximal sigmoid colon is divided above
      the most proximal extent of gross tumor using a ligating and dividing stapling
      device. The sigmoid mesentery is ligated and divided including the superior
      rectal vessels. The pararectal and retrorectal spaces are further developed and
      dissected down to the level of the pelvic floor. The posterior dissection is
      progressed and moves to the right and then to the left of the rectum. The rectal
      pillars including the middle rectal vessels are ligated and divided. Hysterectomy
      is completed in a retrograde fashion. The distal rectum is divided using a linear
      stapler. The specimen is removed en bloc with the uterus, adnexa, pelvic
      peritoneum, rectosigmoid colon, and tumor masses leaving a macroscopically tumor
      free pelvis. Colorectal anastomosis was completed using stapling device. RESULTS:
      En bloc pelvic resection was performed by total abdominal hysterectomy, bilateral
      salpingo-oophorectomy, pelvic peritonectomy, and rectosigmoid colectomy with
      colorectal anastomosis using a stapling device. Complete clearance of pelvic
      disease leaving no gross residual disease was possible using en bloc pelvic
      resection. CONCLUSION: En bloc pelvic resection is effective for achieving
      maximal cytoreduction with the elimination of the pelvic disease in advanced
      primary ovarian cancer patients with extensive pelvic organ involvement.

PMID- 25872896
TI  - Major clinical research advances in gynecologic cancer in 2014.
AB  - In 2014, 9 topics were selected as major advances in clinical research for
      gynecologic oncology: 2 each in cervical and corpus cancer, 4 in ovarian cancer,
      and 1 in breast cancer. For cervical cancer, several therapeutic agents showed
      viable antitumor clinical response in recurrent and metastatic disease:
      bevacizumab, cediranib, and immunotherapies including human papillomavirus (HPV)
      tumor infiltrating lymphocytes and Z-100. The HPV test received FDA approval as
      the primary screening tool of cervical cancer in women aged 25 and older, based
      on the results of the ATHENA trial, which suggested that the HPV test was a more
      sensitive and efficient strategy for cervical cancer screening than methods based
      solely on cytology. For corpus cancers, results of a phase III Gynecologic
      Oncology Group (GOG) 249 study of early-stage endometrial cancer with high
      intermediate risk factors are followed by the controversial topic of uterine
      power morcellation in minimally invasive gynecologic surgery. Promising results
      of phase II studies regarding the effectiveness of olaparib in various ovarian
      cancer settings are summarized. After a brief review of results from a phase III
      study on pazopanib maintenance therapy in advanced ovarian cancer, 2 outstanding
      2014 ASCO presentations cover the topic of using molecular subtypes in predicting
      response to bevacizumab. A review of the use of opportunistic bilateral
      salpingectomy as an ovarian cancer preventive strategy in the general population
      is presented. Two remarkable studies that discussed the effectiveness of adjuvant
      ovarian suppression in premenopausal early breast cancer have been selected as
      the last topics covered in this review. 

PMID- 25872897
TI  - The utility of the 3D imaging software in the macroscopic rendering of complex
      gynecologic specimens.

PMID- 25872898
TI  - The genetic aspects of berries: from field to health.
AB  - Berries are a relevant source of micronutrients and nonessential phytochemicals,
      such as polyphenol compounds, that play a synergistic and cumulative role in
      human health promotion. Several systematic analyses showed that berry phenolics
      are able to detoxify reactive oxygen and nitrogen species, blocking their
      production, to intervene in the cell cycle, participating in the transduction and
      expression of genes involved in apoptosis, and to repair oxidative DNA damage. As
      a consequence, the improvement of the nutritional quality of berries has become a
      new quality target of breeding and biotechnological strategies, to control or to
      increase the content of specific health-related compounds in fruits. This work
      reviews, on the basis of the in vitro and in vivo evidence, the main berries'
      phytochemical compounds and their possible mechanisms of action on pathways
      involved in several type of diseases, with particular attention to cancer,
      inflammation, neurodegeneration, diabetes and cardiovascular diseases.

PMID- 25872899
TI  - The neural basis of the abnormal self-referential processing and its impact on
      cognitive control in depressed patients.
AB  - Persistent pondering over negative self-related thoughts is a central feature of
      depressive psychopathology. In this study, we sought to investigate the neural
      correlates of abnormal negative self-referential processing (SRP) in patients
      with Major Depressive Disorder and its impact on subsequent cognitive control
      related neuronal activation. We hypothesized aberrant activation dynamics during
      the period of negative and neutral SRP in the rostral anterior cingulate cortex
      (rACC) and in the amygdala in patients with major depressive disorder.
      Additionally, we assumed abnormal activation in the fronto-cingulate network
      during Stroop task execution. 19 depressed patients and 20 healthy controls
      participated in the study. Using an event-related functional magnetic resonance
      imaging (fMRI) design, negative, positive and neutral self-referential statements
      were displayed for 6.5 s and followed by incongruent or congruent Stroop
      conditions. The data were analyzed with SPM8. In contrast to controls, patients
      exhibited no significant valence-dependent rACC activation differences during
      SRP. A novel finding was the significant activation of the amygdala and the
      reward-processing network during presentation of neutral self-referential stimuli
      relative to baseline and to affective stimuli in patients. The fMRI analysis of
      the Stroop task revealed a reduced BOLD activation in the right fronto-parietal
      network of patients in the incongruent condition after negative SRP only. Thus,
      the inflexible activation in the rACC may correspond to the inability of
      depressed patients to shift their attention away from negative self-related
      stimuli. The accompanying negative affect and task-irrelevant emotional
      processing may compete for neuronal resources with cognitive control processes
      and lead thereby to deficient cognitive performance associated with decreased
      fronto-parietal activation.

PMID- 25872900
TI  - Applications of physiologically based pharmacokinetic modeling for the
      optimization of anti-infective therapies.
AB  - INTRODUCTION: The pharmacokinetic properties of anti-infective drugs are a
      determinant part of treatment success. Pathogen replication is inhibited if
      adequate drug levels are achieved in target sites, whereas excessive drug
      concentrations linked to toxicity are to be avoided. Anti-infective distribution
      can be predicted by integrating in vitro drug properties and mathematical
      descriptions of human anatomy in physiologically based pharmacokinetic models.
      This method reduces the need for animal and human studies and is used
      increasingly in drug development and simulation of clinical scenario such as, for
      instance, drug-drug interactions, dose optimization, novel formulations and
      pharmacokinetics in special populations. AREAS COVERED: We have assessed the
      relevance of physiologically based pharmacokinetic modeling in the anti-infective
      research field, giving an overview of mechanisms involved in model design and
      have suggested strategies for future applications of physiologically based
      pharmacokinetic models. EXPERT OPINION: Physiologically based pharmacokinetic
      modeling provides a powerful tool in anti-infective optimization, and there is
      now no doubt that both industry and regulatory bodies have recognized the
      importance of this technology. It should be acknowledged, however, that major
      challenges remain to be addressed and that information detailing disease group
      physiology and anti-infective pharmacodynamics is required if a personalized
      medicine approach is to be achieved.

PMID- 25872901
TI  - Pregnancy continuation and organizational religious activity following prenatal
      diagnosis of a lethal fetal defect are associated with improved psychological
      outcome.
AB  - OBJECTIVE: The aim of the article is to examine the psychological impact,
      specifically symptoms of grief, post-traumatic stress and depression, in women
      and men who either terminated or continued a pregnancy following prenatal
      diagnosis of a lethal fetal defect. METHOD: This project investigated a
      diagnostically homogeneous group composed of 158 women and 109 men who lost a
      pregnancy to anencephaly, a lethal neural tube defect. Participants completed the
      Perinatal Grief Scale, Impact of Event Scale - Revised and Beck Depression
      Inventory-II, which measure symptoms of grief, post-traumatic stress and
      depression, respectively. Demographics, religiosity and pregnancy choices were
      also collected. Gender-specific analysis of variance was performed for instrument
      total scores and subscales. RESULTS: Women who terminated reported significantly
      more despair (p = 0.02), avoidance (p = 0.008) and depression (p = 0.04) than
      women who continued the pregnancy. Organizational religious activity was
      associated with a reduction in grief (Perinatal Grief Scale subscales) in both
      women (p = 0.02, p = 0.04 and p = 0.03) and men (p = 0.047). CONCLUSION: There
      appears to be a psychological benefit to women to continue the pregnancy
      following a lethal fetal diagnosis. Following a lethal fetal diagnosis, the risks
      and benefits, including psychological effects, of termination and continuation of
      pregnancy should be discussed in detail with an effort to be as nondirective as
      possible.

PMID- 25872902
TI  - Use of smartphones and mobile devices in hospitalized patients: Untapped
      opportunities for inpatient engagement.

PMID- 25872903
TI  - Study of Electronic, Optical Absorption and Emission in Pure and Metal-Decorated
      Graphene Nanoribbons (C29 H14 -X; X=Ni, Fe, Ti, Co(+) , Al(+) , Cu(+) ): First
      Principles Calculations.
AB  - Density functional theory (DFT) and time-dependent density functional theory
      (TDDFT) calculations were performed with the basis sets 6-31G for DFT and 6
      31G(d), 6-31+G(d,p) for TDDFT on pure graphene nanoribbon (GNR) C30 H14 and metal
      decorated C29 H14 -X (MGNRs; X=Ni, Fe, Ti, Co(+) , Al(+) , and Cu(+) ). The
      metal/carbon ratio (X:C 3.45 %) and the doping site were fixed. Electronic
      properties, that is, the dipole moment, binding energy, and HOMO-LUMO gaps, were
      calculated. The absorption and emission properties in the visible range
      (lambda=400-720 nm) were determined. Optical gaps, absorption and emission
      wavelengths, oscillator strengths, and dominant transitions were calculated. Pure
      graphene was found to be the most stable form. However, of the MGNRs, C29 H14
      ?Co(+) and C29 H14 ?Al(+) were found to be the most and least stable,
      respectively. All GNRs were found to have semiconducting nature. The optical
      absorption of pure graphene undergoes a shift on metal doping. Emission from the
      pure graphene followed Kasha's rule, unlike the metal-doped GNRs. 

PMID- 25872904
TI  - Comparison of the usefulness of heart rate variability versus exercise stress
      testing for the detection of myocardial ischemia in patients without known
      coronary artery disease.
AB  - Heart rate variability (HRV) has been shown to be attenuated in patients with
      coronary artery disease (CAD) and may, therefore, be possibly used for the early
      detection of myocardial ischemia. We aimed to evaluate the diagnostic yield of a
      novel short-term HRV algorithm for the detection of myocardial ischemia in
      subjects without known CAD. We prospectively enrolled 450 subjects without known
      CAD who were referred to tertiary medical centers for exercise stress testing
      (EST) with single-photon emission computed tomography myocardial perfusion
      imaging (MPI). All subjects underwent 1-hour Holter testing with subsequent HRV
      analysis before EST with MPI. The diagnostic yield of HRV analysis was compared
      with EST, using MPI as the gold standard for the noninvasive detection of
      myocardial ischemia. All subjects had intermediate pretest probability for CAD.
      Mean age was 62 years, 38% were women, 51% had hypertension, and 25% diabetes
      mellitus. HRV analysis showed superior sensitivity (77%) compared with standard
      EST (27%). After multivariate adjustment, HRV was independently associated with
      an 8.4-fold (p <0.001) increased likelihood for the detection of myocardial
      ischemia by MPI, whereas EST did not show a statistically significant association
      with a positive MPI (odds ratio 2.1; p = 0.12). Of subjects who were referred for
      subsequent coronary angiography, the respective sensitivities of HRV and EST for
      the detection of significant CAD were 73% versus 26%. Our data suggest that HRV
      can be used as an important noninvasive technique for the detection of myocardial
      ischemia in subjects without known CAD, providing superior sensitivity to
      conventional EST in this population. 

PMID- 25872906
TI  - Recyclable Bifunctional Polystyrene and Silica Gel-Supported Organocatalyst for
      the Coupling of CO2 with Epoxides.
AB  - A bifunctional ammonium salt covalently bound to a polystyrene or silica support
      proved to be an efficient and recyclable catalyst for the solvent-free synthesis
      of cyclic carbonates from epoxides and CO2 . The catalyst can be easily recovered
      by simple filtration after the reaction and reused in up to 13 consecutive runs
      with retention of high activity and selectivity even at 90  degrees C. The scope
      and limitations of the reaction has been evaluated in terms of reaction
      conditions and substrate scope.

PMID- 25872907
TI  - The effect of structure directing agents on the ordering of fluoride ions in pure
      silica MFI zeolites.
AB  - The effect of different sizes of structure directing agents on the ordering of
      the fluoride ions in pure silica MFI zeolites has been determined using magic
      angle spinning solid state NMR. By synthesizing fluoride containing pure silica
      MFI zeolites using methyltributylammonium cations as the structure directing
      agent, it has been possible to change the type of ordering seen for the fluoride
      ions at room temperature from the previously reported dynamic to static disorder.
      An initial mechanism for how this fluoride ordering occurs is suggested based
      upon the coulombic interaction between the positive charge on the nitrogen and
      the negative fluoride ion, within the zeolite framework, with different sizes of
      tetraalkylammonium cations. 

PMID- 25872909
TI  - A cross-kingdom history.

PMID- 25872908
TI  - Involvement of a C-terminal motif in the interference of primate lentiviral Vpu
      proteins with CD1d-mediated antigen presentation.
AB  - The HIV-1 accessory protein Vpu is emerging as a critical factor for viral
      evasion from innate immunity. We have previously shown that the Vpu proteins of
      two HIV-1 group M subtype B strains (NL4-3 and BaL) down-regulate CD1d from the
      surface of infected dendritic cells (DCs) and inhibit their crosstalk with the
      innate invariant natural killer T (iNKT) cells. In the present study, we have
      investigated the ability of a comprehensive set of primate lentiviral Vpu
      proteins to interfere with CD1d-mediated immunity. We found that CD1d down
      regulation is a conserved function of Vpu proteins from HIV-1 groups M, O and P
      as well as their direct precursors SIVcpzPtt and SIVgor. At the group M subtype
      level, subtype C Vpu proteins were significantly weaker CD1d antagonists than
      subtype B Vpu proteins. Functional characterization of different mutants and
      chimeras derived from active subtype B and inactive subtype C Vpu proteins
      revealed that residues in the cytoplasmic domain are important for CD1d down
      regulation. Specifically, we identified a C-terminal APW motif characteristic for
      group M subtype B Vpu proteins necessary for interference with CD1d surface
      expression. These findings support the notion that Vpu plays an important role in
      lentiviral evasion from innate immunity. 

PMID- 25872910
TI  - Length and weight of very low birth weight infants in Germany at 2 years of age:
      does it matter at what age they start complementary food?
AB  - BACKGROUND/OBJECTIVES: We analysed at what age parents start complementary food
      in very low birth weight infants, determined risk factors for early introduction
      of complementary food (post-term age) and analysed whether the age at
      introduction of complementary food influences height or weight at 2 years of age.
      SUBJECTS/METHODS: Parents of premature infants born in 2009-2011 answered
      questionnaires regarding introduction of complementary food in the first year of
      life (N=2262) and were followed up at a post-term age of 2 years (N=981). Length
      and weight were compared with full-term infants from the KiGGs study. Logistic
      and linear regression analyses were conducted to study predictors for early
      introduction of complementary food and the influence of age at introduction of
      complementary food on later height and weight. RESULTS: Average age at
      introduction of complementary food was 3.5 months post-term age. The lower the
      gestational age at birth, the earlier (post-term age) vegetables and meat were
      introduced. Age at introduction of complementary food was influenced by
      intrauterine growth restriction, gestational age at birth, maternal education and
      a developmental delay perceived by the parents. Length and weight at a post-term
      age of 2 years was not negatively influenced by early introduction of
      complementary food. CONCLUSIONS: VLBW infants are introduced to complementary
      food on average before a post-term age of 4 months. There was no negative effect
      of early introduction of complementary food on height and weight at 2 years of
      age.

PMID- 25872912
TI  - Rhodium(III)-Catalyzed [3+2]/[5+2] Annulation of 4-Aryl 1,2,3-Triazoles with
      Internal Alkynes through Dual C(sp2)-H Functionalization.
AB  - A rhodium(III)-catalyzed [3+2]/[5+2] annulation of 4-aryl 1-tosyl-1,2,3-triazoles
      with internal alkynes is presented. This transformation provides straightforward
      access to indeno[1,7-cd]azepine architectures through a sequence involving the
      formation of a rhodium(III) azavinyl carbene, dual C(sp(2))-H functionalization,
      and [3+2]/[5+2] annulation.

PMID- 25872911
TI  - Association between dietary patterns in the remote past and telomere length.
AB  - BACKGROUND/OBJECTIVES: There are limited data on the association between dietary
      information and leukocyte telomere length (LTL), which is considered an indicator
      of biological aging. In this study, we aimed at determining the association
      between dietary patterns or consumption of specific foods and LTL in Korean
      adults. SUBJECT/METHODS: A total of 1958 middle-aged and older Korean adults from
      a population-based cohort were included in the study. Dietary data were collected
      from a semi-quantitative food frequency questionnaire at baseline (June 2001 to
      January 2003). LTL was assessed using real-time PCR during the 10-year follow-up
      period (February 2011 to November 2012). RESULTS: We identified two major factors
      and generated factor scores using factor analysis. The first factor labeled
      'prudent dietary pattern' was characterized by high intake of whole grains,
      seafood, legumes, vegetables and seaweed, whereas the second factor labeled
      'Western dietary pattern' was characterized by high intake of refined grain, red
      meat or processed meat and sweetened carbonated beverages. In a multiple linear
      regression model adjusted for age, sex, body mass index and other potential
      confounding variables, the prudent dietary pattern was positively associated with
      LTL. In the analysis of particular food items, higher consumption of legumes,
      nuts, seaweed, fruits and dairy products and lower consumption of red meat or
      processed meat and sweetened carbonated beverages were associated with longer
      LTL. CONCLUSIONS: Our findings suggest that diet in the remote past, that is, 10
      years earlier, may affect the degree of biological aging in middle-aged and older
      adults.

PMID- 25872913
TI  - Identification of two novel Darier disease-associated mutations in the ATP2A2
      gene.
AB  - Darier disease (DD) is an autosomal dominant inherited skin disorder,
      characterized by abnormal keratinization, loss of adhesion between epidermal
      cells, termed acantholysis, and the development of warty papules and plaques on
      the central trunk, forehead, scalp and flexures. These symptoms are often
      exacerbated by heat, sweating, sunburn and stress. Mutations in the ATP2A2 gene,
      encoding SERCA2, a calcium pump of the sarco/endoplasmic reticulum, are
      responsible for the disease. The aim of the present study was to investigate two
      pedigrees of DD and to examine the genetic mutations. DNA was extracted from
      peripheral blood, which was obtained from four patients with DD, 10 healthy
      individuals from the two families and 100 ethnicity-matched control individuals,
      on which subsequent polymerase chain reaction amplification and direct automated
      DNA sequencing were performed. The results identified two novel missense
      mutations, p.R603I and p.G749 V. These mutations were not identified in the
      remaining ten healthy individuals in the same families or in any of the 100
      controls. These mutations may contribute to the expanding database of ATP2A2 gene
      mutations in patients with DD.

PMID- 25872914
TI  - Minimal packing duration in close reduction for nasal bone fracture treatment.
AB  - PURPOSE: Nasal bone fracture is the most common type of facial bone fracture. The
      optimal duration of the packing after closed reduction has been a controversial
      issue. The packing has several disadvantages such as blocking the nasal airway,
      causing infection and a headache, which is the most common immediate
      complication. The present study investigated the minimal and optimal duration of
      the nasal packing following reduction surgery of nasal bone fracture. METHODS: A
      prospective study was performed for the patients undergoing reduction surgery
      following nasal bone fracture between July 2010 and June 2012. The patients were
      categorised into three groups according to the duration of nasal packing. For the
      patients treated between July 2010 and June 2011, nasal packing was maintained
      for 5 days. For those between July 2011 and December 2011, packing was maintained
      for 3 days. For those between January 2012 and June 2012, the packing was removed
      after 1 day. The computed tomography scan and the cephalolateral X-ray were
      checked at immediate postoperative period after packing removal and 6 months
      postoperatively. The alteration of heights, deviations, and nasal bone contours
      with time passage were compared among three groups. The patient satisfaction
      survey was also performed and compared. RESULTS: A total of 530 patients
      including 322 of the 5-days packing group, 102 of the 3-days group, and 106 of
      the 1-day group were enrolled. There was no statistically significant difference
      between the groups in terms of heights, deviations, and nasal bone contours (p
      value >= 0.05). In the patient satisfaction survey, the 1-day packing group
      complained of discomfort related to nasal packing and headache symptoms much
      less, compared to the other two groups. CONCLUSION: The present study
      demonstrated that 1-day packing had comparable postoperative outcome with
      reducing the patients' discomfort. As such, a longer packing duration was not
      needed to achieve stable results one day is a reasonable packing time for most
      nasal bone fractures.

PMID- 25872915
TI  - Antibody glycosylation and its impact on the pharmacokinetics and
      pharmacodynamics of monoclonal antibodies and Fc-fusion proteins.
AB  - Understanding the impact of glycosylation and keeping a close control on
      glycosylation of product candidates are required for both novel and biosimilar
      monoclonal antibodies (mAbs) and Fc-fusion protein development to ensure proper
      safety and efficacy profiles. Most therapeutic mAbs are of IgG class and contain
      a glycosylation site in the Fc region at amino acid position 297 and, in some
      cases, in the Fab region. For Fc-fusion proteins, glycosylation also frequently
      occurs in the fusion partners. Depending on the expression host, glycosylation
      patterns in mAb or Fc-fusions can be significantly different, thus significantly
      impacting the pharmacokinetics (PK) and pharmacodynamics (PD) of mAbs. Glycans
      that have a major impact on PK and PD of mAb or Fc-fusion proteins include
      mannose, sialic acids, fucose (Fuc), and galactose (Gal). Mannosylated glycans
      can impact the PK of the molecule, leading to reduced exposure and potentially
      lower efficacy. The level of sialic acid, N-acetylneuraminic acid (NANA), can
      also have a significant impact on the PK of Fc-fusion molecules. Core Fuc in the
      glycan structure reduces IgG antibody binding to IgG Fc receptor IIIa relative to
      IgG lacking Fuc, resulting in decreased antibody-dependent cell-mediated
      cytotoxicity (ADCC) activities. Glycoengineered Chinese hamster ovary (CHO)
      expression systems can produce afucosylated mAbs that have increased ADCC
      activities. Terminal Gal in a mAb is important in the complement-dependent
      cytotoxicity (CDC) in that lower levels of Gal reduce CDC activity. Glycans can
      also have impacts on the safety of mAb. mAbs produced in murine myeloma cells
      such as NS0 and SP2/0 contain glycans such as Galalpha1-3Galbeta1-4N
      acetylglucosamine-R and N-glycolylneuraminic acid (NGNA) that are not naturally
      present in humans and can be immunogenic when used as therapeutics.

PMID- 25872916
TI  - Altered Corticostriatal Connectivity and Exploration/Exploitation Imbalance
      Emerge as Intermediate Phenotypes for a Neonatal Dopamine Dysfunction.
AB  - Findings showing that neonatal lesions of the forebrain dopaminergic system in
      rodents lead to juvenile locomotor hyperactivity and learning deficits have been
      taken as evidence of face validity for the attention deficit hyperactivity
      disorder. However, the core cognitive and physiological intermediate phenotypes
      underlying this rodent syndrome remain unknown. Here we show that early postnatal
      dopaminergic lesions cause long-lasting deficits in exploitation of shelter,
      social and nutritional resources, and an imbalanced exploratory behavior, where
      nondirected local exploration is exacerbated, whereas sophisticated search
      behaviors involving sequences of goal directed actions are degraded. Importantly,
      some behavioral deficits do not diminish after adolescence but instead worsen or
      mutate, particularly those related to the exploration of wide and spatially
      complex environments. The in vivo electrophysiological recordings and
      morphological reconstructions of striatal medium spiny neurons reveal
      corticostriatal alterations associated to the behavioral phenotype. More
      specifically, an attenuation of corticostriatal functional connectivity,
      affecting medial prefrontal inputs more markedly than cingulate and motor inputs,
      is accompanied by a contraction of the dendritic arbor of striatal projection
      neurons in this animal model. Thus, dopaminergic neurons are essential during
      postnatal development for the functional and structural maturation of
      corticostriatal connections. From a bottom-up viewpoint, our findings suggest
      that neuropsychiatric conditions presumably linked to developmental alterations
      of the dopaminergic system should be evaluated for deficits in foraging decision
      making, alterations in the recruitment of corticostriatal circuits during
      foraging tasks, and structural disorganization of the frontostriatal connections.

PMID- 25872917
TI  - Nucleus Accumbens and Posterior Amygdala Mediate Cue-Triggered Alcohol Seeking
      and Suppress Behavior During the Omission of Alcohol-Predictive Cues.
AB  - Neurobiological mechanisms that influence behavior in the presence of alcohol
      associated stimuli involve processes that organize behavior during the presence
      of these cues, and separately, regulation of behavior in their absence. However,
      little is known about anatomical structures that might mediate this regulation.
      Here we examined nucleus accumbens shell (AcbSh) as a possible neural substrate
      mediating behavior modulation triggered by the presence and absence of alcohol
      associated environmental cues and contexts. We also examined subregions of basal
      amygdala nuclei- rostral basolateral (BLA) and basal posterior (BAP)- as they
      provide a major source of glutamatergic input to the AcbSh. Animals were trained
      to associate an auditory conditioning stimulus with alcohol in a discriminative
      context and then subsequently tested for conditioned port-entries across contexts
      either previously associated or not associated with alcohol. We found that, on
      test to the alcohol cue alone, AcbSh inactivation prevented conditioned port
      entries in contexts that either were associated with alcohol or were novel, while
      also increasing unconditioned port-entries during the intertrial intervals. When
      tested to alcohol-reinforced cues, AcbSh inactivation produced more cue-trial
      omissions and elevated unconditioned port-entries. Interestingly, BLA and BAP
      inactivation produced dissociable effects. BAP but not BLA increased
      unconditioned port-entries, while both manipulations prevented conditioned port
      entries during the alcohol-cue. We conclude that AcbSh is necessary for
      modulating control over behavior otherwise guided by the presence of alcohol
      predictive environmental stimuli and contexts. Moreover, this role may involve
      integration of functionally segregated inputs from rostral and posterior portions
      of basal amygdala nuclei.

PMID- 25872918
TI  - Dissociation of the Role of Infralimbic Cortex in Learning and Consolidation of
      Extinction of Recent and Remote Aversion Memory.
AB  - Medial prefrontal circuits have been reported to undergo a major reorganization
      over time and gradually take a more important role for remote emotional memories
      such as contextual fear memory or food aversion memory. The medial prefrontal
      cortex, and specifically its ventral subregion, the infralimbic cortex (IL), was
      also reported to be critical for recent memory extinction of contextual fear
      conditioning and conditioned odor aversion. However, its exact role in the
      extinction of remotely acquired information is still not clear. Using
      postretrieval blockade of protein synthesis or inactivation of the IL, we showed
      that the IL is similarly required for extinction consolidation of recent and
      remote fear memory. However, in odor aversion memory, the IL was only involved in
      extinction consolidation of recent, but not remote, memory. In contrast, only
      remote retrieval of aversion memory induced c-Fos activation in the IL and
      preretrieval inactivation of the IL with lidocaine impaired subsequent extinction
      of remote but not recent memory, indicating IL is necessary for extinction
      learning of remote aversion memory. In contrast to the effects in odor aversion,
      our data show that the involvement of the IL in the consolidation of fear
      extinction does not depend on the memory age. More importantly, our data indicate
      that the IL is implicated in the extinction of fear and nonfear-based
      associations and suggest dissociation in the engagement of the IL in the learning
      and consolidation of food aversion extinction over time. 

PMID- 25872920
TI  - The unusual magnetism of nanoparticle LaCoO3.
AB  - Bulk and nanoparticle powders of LaCoO3 (LCO) were synthesized and their magnetic
      and structural properties were studied using SQUID magnetometry and neutron
      diffraction. The bulk and large nanoparticles exhibit weak ferromagnetism (FM)
      below T ~ 85 K and a crossover from strong to weak antiferromagnetic (AFM)
      correlations near a transition expressed in the lattice parameters, To~40 K. This
      crossover does not occur in the smallest nanoparticles; instead, the magnetic
      behavior is predominantly ferromagnetic. The amount of FM in the nanoparticles
      depends on the amount of Co3O4 impurity phase, which induces tensile strain on
      the LCO lattice. A core-interface model is introduced, with the core region
      exhibiting the AFM crossover and with FM in the interface region near surfaces
      and impurity phases. 

PMID- 25872919
TI  - Efficient light emission from inorganic and organic semiconductor hybrid
      structures by energy-level tuning.
AB  - The fundamental limits of inorganic semiconductors for light emitting
      applications, such as holographic displays, biomedical imaging and ultrafast data
      processing and communication, might be overcome by hybridization with their
      organic counterparts, which feature enhanced frequency response and colour range.
      Innovative hybrid inorganic/organic structures exploit efficient electrical
      injection and high excitation density of inorganic semiconductors and subsequent
      energy transfer to the organic semiconductor, provided that the radiative
      emission yield is high. An inherent obstacle to that end is the unfavourable
      energy level offset at hybrid inorganic/organic structures, which rather
      facilitates charge transfer that quenches light emission. Here, we introduce a
      technologically relevant method to optimize the hybrid structure's energy levels,
      here comprising ZnO and a tailored ladder-type oligophenylene. The ZnO work
      function is substantially lowered with an organometallic donor monolayer,
      aligning the frontier levels of the inorganic and organic semiconductors. This
      increases the hybrid structure's radiative emission yield sevenfold, validating
      the relevance of our approach. 

PMID- 25872922
TI  - The European stroke organisation - annual conference, glasgow, 17th - 19th april,
      2015.

PMID- 25872921
TI  - Low resting heart rates are associated with new-onset atrial fibrillation in
      patients with vascular disease: results of the ONTARGET/TRANSCEND studies.
AB  - BACKGROUND: Elevated systolic blood pressure (SBP) and high resting heart rate
      (HR) are associated with cardiovascular end-points. Although the association
      between atrial fibrillation (AF) and SBP is well established, the relation
      between AF and HR remains unclear. METHODS: In patients from the ONTARGET and
      TRANSCEND studies with high cardiovascular disease risk (n = 27 064), new-onset
      AF was evaluated in relation to mean SBP, visit-to-visit variation in SBP (SBP
      CV; i.e. SD/mean * 100%), mean HR and visit-to-visit variation in HR (HR-CV).
      RESULTS: Low mean HR (P < 0.0001) and high SBP (P = 0.0021) were associated with
      incident AF. High SBP-CV (P = 0.031) and HR-CV (P < 0.0001) were also associated
      with incident AF. After adjustment for confounders, SBP and SBP-CV were no longer
      significantly associated with AF. The detrimental effect of low HR was
      particularly evident in subjects who were not receiving treatment with beta
      blockers (P = 0.014 for interaction between beta-blocker use and mean HR). In
      addition to low HR, high HR-CV and high SBP had additive effects on incident AF.
      CONCLUSIONS: Low mean HR (<60 beats min(-1) ) is independently associated with
      incident AF, and low HR-CV and high SBP further increase the incidence of new
      onset AF in patients at high risk of cardiovascular disease.

PMID- 25872923
TI  - MAGE-A expression clusters and antineoplastic treatment in head and neck cancer.
AB  - The nonsurgical treatment of head and neck squamous cell carcinoma (HNSCC)
      usually consists of radiation and chemotherapy. In general, the treatment
      efficacy of chemotherapy in head and neck cancer is limited. Apart from the
      placenta, testis and fetal keratinocytes, melanoma-associated antigens-A (MAGE-A)
      are only found in malignancies. Even though their molecular role remains unclear,
      several subgroups have been found to contribute to resistance to different
      chemotherapeutic agents. In the present study, established human squamous cell
      carcinoma cell lines were incubated with various concentrations of cisplatin, 5
      fluorouracil, paclitaxel, docetaxel, cetuximab and panitumumab for 5, 10, 20 and
      40 h. The treatment efficacy was measured dynamically by real-time cell analysis
      (RTCA). In addition, we determined the expression of all known MAGE-A subgroups
      (MAGE-A1 to MAGE-A12, excluding pseudogene MAGE-A7) by reverse transcription
      quantitative polymerase chain reaction. Of note, one cell line showed only a
      marginal expression of MAGE-A antigens, whereas another cell line showed a
      distinct expression of almost all the MAGE-A subgroups. The expression pattern
      varied in the other cell lines. MAGE-A4 was the most highly expressed of all the
      subgroups, and MAGE-A8 could not be detected. With the exception of MAGE-A6, -A8,
      -A9 and -A10, the expression levels differed significantly between the cell
      lines. Factor analysis suggested simplifying the MAGE-A expression level into two
      groups. Spearman's rank correlation revealed a significant association between
      MAGE-A expression and treatment efficacy for 20.8% (25/120) of the experiments.
      In 100% of these cases (25/25), Spearman's Rho revealed a positive correlation
      between clustered MAGE-A expression and poor treatment efficacy. Our data
      highlight the fact that higher a MAGE-A expression correlates with a poorer
      outcome of antineoplastic treatment. Clustered MAGE-A expression analysis may
      help to identify patients who are at a higher risk of antineoplastic treatment
      failure.

PMID- 25872924
TI  - Versican silencing improves the antitumor efficacy of endostatin by alleviating
      its induced inflammatory and immunosuppressive changes in the tumor
      microenvironment.
AB  - The systematic application of antiangiogenic therapy remains an issue of concern,
      mainly due to the hypoxic and inflammatory changes in the tumor microenvironment
      elicited by antiangiogenic therapy. Versican, a 'bridge' connecting inflammation
      with tumor progression as well as playing a central role in the generation of an
      inflammatory tumor microenvironment is a promising candidate for the intervention
      of inflammatory changes in the tumor microenvironment elicited by antiangiogenic
      therapy. To examine this hypothesis, a short-hairpin RNA targeting versican
      (shVCAN) was designed and shVCAN stable-transfected B16F1 and Lewis lung
      carcinoma (LLC) cell lines were established. Simultaneously, the established
      B16F1 and LLC tumor models were used to investigate the effect of versican
      silencing on the tumor burden of mice. The results showed that, versican
      silencing exerted an inhibitory effect on the proliferative and migratory ability
      of B16F1 cells, but did not affect LLC cells. Endostatin exhibited modest
      inhibition of tumor growth in tumor-bearing mice. Versican silencing alone
      effectively suppressed orthotopic tumor growth and significantly prolonged
      survival time of mice more effectively when combined with endostatin. Endostatin
      elicited inflammatory and immunosuppressive changes in the tumor
      microenvironment, including an accumulation of myeloid-derived suppressor cells
      (MDSCs), tumor-associated macrophages (TAMs) and inflammatory cytokines. In
      addition, NF-kappaB and HIF-1alpha were overexpressed in the tumor. Versican
      silencing improved the antitumor efficacy of endostatin by alleviating its
      induced changes in the tumor microenvironment. Thus, versican silencing in the
      tumor microenvironment offers a promising approach to reverse the tumor
      refractoriness to antiangiogenic therapies.

PMID- 25872926
TI  - Ebola remains an international health emergency, WHO warns.

PMID- 25872925
TI  - Investigating the non-specific effects of BCG vaccination on the innate immune
      system in Ugandan neonates: study protocol for a randomised controlled trial.
AB  - BACKGROUND: The potential for Bacillus Calmette-Guerin (BCG) vaccination to
      protect infants against non-mycobacterial disease has been suggested by a
      randomised controlled trial conducted in low birth-weight infants in West Africa.
      Trials to confirm these findings in healthy term infants, and in a non-West
      African setting, have not yet been carried out. In addition, a biological
      mechanism to explain such heterologous effects of BCG in the neonatal period has
      not been confirmed. This trial aims to address these issues by evaluating whether
      BCG non-specifically enhances the innate immune system in term Ugandan neonates,
      leading to increased protection from a variety of infectious diseases. METHODS:
      This trial will be an investigator-blinded, randomised controlled trial of 560
      Ugandan neonates, comparing those receiving BCG at birth with those receiving BCG
      at 6 weeks of age. This design allows comparison of outcomes between BCG
      vaccinated and -naive infants until 6 weeks of age, and between early and delayed
      BCG-vaccinated infants from 6 weeks of age onwards. The primary outcomes of the
      study will be a panel of innate immune parameters. Secondary outcomes will
      include clinical illness measures. DISCUSSION: Investigation of the possible
      broadly protective effects of neonatal BCG immunisation, and the optimal
      vaccination timing to produce these effects, could have profound implications for
      public healthcare policy. Evidence of protection against heterologous pathogens
      would underscore the importance of prioritising BCG administration in a timely
      manner for all infants, provide advocacy against the termination of BCG's use and
      support novel anti-tuberculous vaccine strategies that would safeguard such
      beneficial effects. TRIAL REGISTRATION: ISRCTN59683017 : registration date: 15
      January 2014.

PMID- 25872927
TI  - Sharing data from clinical trials: the rationale for a controlled access
      approach.
AB  - BACKGROUND: The move towards increased transparency around clinical trials is
      welcome. Much focus has been on under-reporting of trials and access to
      individual patient data to allow independent verification of findings. There are
      many other good reasons for data sharing from clinical trials. We describe some
      key issues in data sharing, including the challenges of open access to data.
      These include issues in consent and disclosure; risks in identification,
      including self-identification; risks in distorting data to prevent self
      identification; and risks in analysis. These risks have led us to develop a
      controlled access policy, which safeguards the rights of patients entered in our
      trials, guards the intellectual property rights of the original researchers who
      designed the trial and collected the data, provides a barrier against unnecessary
      duplication, and ensures that researchers have the necessary resources and skills
      to analyse the data. METHODS: We briefly discuss the practicalities of our
      current approach to data sharing, including ensuring that data are discoverable
      and how to deal with old studies. We describe data sharing activities at the MRC
      Clinical Trials Unit. RESULTS: One hundred and three data sharing activities were
      logged from 2012 to 2014 from external and internal applicants. The motivations
      are varied, but none have been for replication of the primary results.
      CONCLUSIONS: For any request to share data, we note the important role of
      independent reviewers as well as reviewers who know the study well, and present
      some of the key questions that all reviewers should ask when deciding whether a
      request is reasonable. We consider the responsibilities of all parties. We
      highlight the potential for opportunity costs. Clinical trial data should be
      shared for reasonable requests but there are many practical issues that must be
      explicitly considered.

PMID- 25872928
TI  - A study protocol for a pilot randomised trial of a structured education programme
      for the self-management of type 2 diabetes for adults with intellectual
      disabilities.
AB  - BACKGROUND: The need for structured education programmes for type 2 diabetes is a
      high priority for many governments around the world. One such national education
      programme in the United Kingdom is the DESMOND Programme, which has been shown to
      be robust and effective for patients in general. However, these programmes are
      not generally targeted to people with intellectual disabilities (ID), and robust
      evidence on their effects for this population is lacking. We have adapted the
      DESMOND Programme for people with ID and type 2 diabetes to produce an amended
      programme known as DESMOND-ID. This protocol is for a pilot trial to determine
      whether a large-scale randomised trial is feasible, to test if DESMOND-ID is more
      effective than usual care in adults with ID for self-management of their type 2
      diabetes, in particular as a means to reduce glycated haemoglobin (Hb1Ac),
      improve psychological wellbeing and quality of life and promote a healthier
      lifestyle. This protocol describes the rationale, methods, proposed analysis plan
      and organisational and administrative details. METHODS/DESIGN: This trial is a
      two arm, individually randomised, pilot trial for adults with ID and type 2
      diabetes, and their family and/or paid carers. It compares the DESMOND-ID
      programme with usual care. Approximately 36 adults with mild to moderate ID will
      be recruited from three countries in the United Kingdom. Family and/or paid
      carers may also participate in the study. Participants will be randomly assigned
      to one of two conditions using a secure computerised system with robust
      allocation concealment. A range of data will be collected from the adults with ID
      (biomedical, psychosocial and self-management strategies) and from their carers.
      Focus groups with all the participants will assess the acceptability of the
      intervention and the trial. DISCUSSION: The lack of appropriate structured
      education programmes and educational materials for this population leads to
      secondary health conditions and may lead to premature deaths. There are
      significant benefits to be gained globally, if structured education programmes
      are adapted and shown to be successful for people with ID and other cognitive
      impairments. TRIAL REGISTRATION: Registered with International Standard
      Randomised Controlled Trial (identifier: ISRCTN93185560 ) on 10 November 2014.

PMID- 25872930
TI  - Zoledronic acid increases bone density but does not reduce fractures in frail
      elderly people, study finds.

PMID- 25872929
TI  - Short-term study on risk-benefit outcomes of two spinal manipulative therapies in
      the treatment of acute radiculopathy caused by lumbar disc herniation: study
      protocol for a randomized controlled trial.
AB  - BACKGROUND: That patients with acute radiculopathy caused by lumbar disc
      herniation (LDH) will benefit from spinal manipulation (SM) treatment has been
      taken for granted, despite no solid evidence to support that claim. There is a
      demand for a win-win SM treatment that is both effective and less risky, and we
      attempt to use this trial to demonstrate such a treatment. In this study, Feng's
      Spinal Manipulative Therapy (FSM) is selected as the observational SM. FSM can be
      performed with either manipulation or mobilization, and also can be easily
      mimicked as a sham SM. METHODS/DESIGN: Two hundred and sixteen qualified
      hospitalized participants will be randomly allocated to one of the three
      following groups: sham SM, mobilization, or manipulation, according to a ratio of
      1:1:1. Participants in each group will receive specific FSM treatments four
      times, along with basic therapies over a course of 2 weeks. Two days after each
      SM appointment, risk outcomes will be assessed using a questionnaire developed to
      identify accompanying unpleasant reactions (AUR). The pain pressure threshold
      (PPT) will be measured paraspinally on the tender spot beside the involved joint
      before and immediately after each SM treatment. Relative risk (RR) of AUR, number
      needed to harm (NNH) and the 95% confidence intervals of each group will be
      calculated and compared. Benefit outcomes will be assessed by analyzing the
      following data recordings: the Numerical Rating Scale (NRS), Oswestry Disability
      Index (ODI), and Global Perceived Effect (GPE) before enrollment and at the 7th,
      and 15th day after the treatment. Analyses will include comparisons of NRS, ODI
      and changes at the different visit times among the three groups by Repeated
      Measures Data ANOVA, an evaluation of reduced scores of NRS and ODI after the
      therapy to determine if they meet the minimum acceptable outcome (MAO), and the
      determination of the minimal clinically important difference (MCID) by the
      average improvement in NRS and ODI scores of all participants who have been
      allocated to the category 'improved' on the GPE assessment. TRIAL REGISTRATION:
      This trial is registered in Chinese Clinical Trial Register (ChiCTR) on 19 August
      2013 ( ChiCTR-TRC-13003496 ).

PMID- 25872931
TI  - Effect and mechanism of poly (ADP-ribose) polymerase-1 in aldosterone-induced
      apoptosis.
AB  - The present study aimed to investigate the effects of aldosterone on vascular
      endothelial cells and the viability of poly (ADP-ribose) polymerase 1 (PARP1) in
      cells, and to examine the molecular mechanisms underlying the effects of
      aldosterone on vascular endothelial cell injury. Cultured endothelial cells were
      treated either with different concentrations of aldosterone for the same duration
      or with the same concentrations of aldosterone for different durations, and the
      levels of apoptosis and activity of PARP1 in the cells were detected,
      respectively. Aldosterone receptor antagonists or PARP1 inhibitors were added to
      cells during treatment with aldosterone and the levels of apoptosis and activity
      of PARP1 were detected. As the concentration of aldosterone increased or the
      treatment time increased, the number of apoptotic cells and the activity of PARP1
      increased. The aldosterone receptor antagonists and PARP1 inhibitors inhibited
      the increase of apoptosis and PARP1 activity caused by aldosterone treatment.
      Aldosterone activated the activity of PARP1 via the aldosterone receptor,
      inhibiting cell proliferation and inducing apoptosis. Treatment with PARP1 may be
      used as a target for vascular diseases caused by aldosterone at high
      concentrations.

PMID- 25872932
TI  - Antenatal screening for Down's syndrome, trisomy 18, and trisomy 13: Reporting a
      single screening result for all three.
AB  - OBJECTIVE: To compare the performance of antenatal screening for Down's syndrome
      (DS), trisomy 18 (T18), and trisomy 13 (T13) using a single risk of being
      affected by one of the three disorders, with the performance using separate risks
      for each disorder. METHODS: Screening performance was estimated using Monte Carlo
      simulation based on published parameters for the Integrated, Combined, and
      Quadruple tests. Detection rates (DRs) were calculated using a single risk and
      separate risks for each disorder at given false-positive rates (FPRs). RESULTS:
      With separate risks, using a 3% DS test FPR and 0.2% FPRs for the T18 and T13
      tests, the overall FPRs for the Integrated and Combined tests are both 3.3%. For
      the same overall FPR (3.3%), the use of a single risk with the Integrated test
      increases the T13 DR from 76% to 82%, with unchanged DS and T18 DRs (94% and 92%
      respectively). With the Combined test, it increases the T13 and T18 DRs (from 89%
      to 91% and 77% to 81% respectively), with unchanged DS DR (85%). With separate
      risks, using a 5% DS test FPR and 0.2% FPRs for the T18 and T13 tests, the
      overall FPR for the Quadruple test is 5.4%. For the same overall FPR (5.4%), the
      use of a single risk increases the T18 DR from 61% to 67% with unchanged DS and
      T13 DRs (87% and 33% respectively). CONCLUSIONS: Reporting a single risk estimate
      for the three disorders is less confusing than reporting separate risks and can
      yield the same or better screening performance.

PMID- 25872933
TI  - Highly Stable and Tunable n-Type Graphene Field-Effect Transistors with
      Poly(vinyl alcohol) Films.
AB  - The intrinsic p-type behavior of graphene field-effect transistors (FETs) under
      ambient conditions poses a fundamental challenge for the assembly of complex
      electronic devices, such as integrated circuits. In this work, we present a
      protocol for tunable n-type doping of graphene FETs via poly(vinyl alcohol) (PVA)
      coating. Using graphene grown by alcohol catalytic chemical vapor deposition,
      functionalization of the surface by this hydroxyl anion-rich polymer results in
      an evolution of the FETs from p-type to ambipolar or n-type even under ambient
      air conditions. The doping level of graphene is strongly related to the PVA film
      coating parameters, such as solution concentration, hardening temperature, and
      hardening time. This PVA coating proves to be a simple and stable approach to
      tuning the Dirac point and doping level of graphene, which is highly desirable
      and of great significance for the future of graphene-based electronic devices. 

PMID- 25872934
TI  - Could enteral nutrition improve the outcome of patients with haematological
      malignancies undergoing allogeneic haematopoietic stem cell transplantation? A
      study protocol for a randomized controlled trial (the NEPHA study).
AB  - BACKGROUND: Myeloablative allogeneic haematopoietic stem cell transplantation
      (allo-HSCT) is a major procedure usually accompanied by multifactorial
      malnutrition, prompting the recommendation of systematic artificial nutritional
      support. Parenteral nutrition (PN) is usually administered during allo-HSCT,
      essentially for practical reasons. Recently published data suggest that enteral
      nutrition (EN), given as systematic artificial nutrition support, could decrease
      grade III-IV graft-versus-host disease (GVHD) and infectious events, which are
      associated with early toxicity after allo-HSCT and then have an impact on early
      transplant-related mortality (D100 mortality). METHODS/DESIGN: We report on the
      NEPHA trial: an open-label, prospective, randomised, multi-centre study on two
      parallel groups, which has been designed to evaluate the effect of EN compared to
      PN on early toxicity after an allo-HSCT procedure. Two hundred forty patients
      treated with allo-HSCT for a haematological malignancy will be randomly assigned
      to two groups to receive either EN or PN. The primary endpoint will assess the
      effect of EN on D100 mortality. Secondary endpoints will compare EN and PN with
      regards to the main haematological, infectious and nutritional outcomes.
      DISCUSSION: The impacts of nutritional support should exceed the limits of
      nutritional status improvement: EN may directly reduce immunological and
      infectious events, as well as decrease early transplant-related morbidity and
      mortality. EN and PN need to be prospectively compared in order to assess their
      impacts and to provide treatment guidelines. (Clinical trials gov number:
      NCT01955772; registration: July 19th, 2013).

PMID- 25872935
TI  - Anaemia prevalence and associated factors among lactating mothers in Ethiopia:
      evidence from the 2005 and 2011 demographic and health surveys.
AB  - OBJECTIVE: To identify factors associated with anaemia in lactating mothers in
      Ethiopia. DESIGN: A cross-sectional secondary analysis of data pooled from two
      rounds of the 2005 and 2011 Ethiopian Demographic and Health Survey (EDHS) was
      used. A multivariate logistic regression model was applied to determine the
      factors associated with anaemia. POPULATION: A total of 7332 lactating mothers
      (2285 from EDHS 2005 and 5047 from EDHS 2011) were included from 11
      administrative states of Ethiopia. MAIN OUTCOME MEASURES: Lactating mothers
      considered anaemic if haemoglobin level <12 g/dL. RESULTS: The overall prevalence
      of anaemia among lactating mothers was 22.1% (95% CI 21.13% to 23.03%). The
      highest prevalence was 48.7% (95% CI 40.80% to 56.62%) found in the Somali
      region, followed by 43.8% (95% CI 31.83% to 56.87%) in the Afar region. The
      multivariate statistical model showed that having a husband who had attended
      primary education (adjusted OR (AOR) 0.79; 95% CI 0.68 to 0.91), working during
      the 12 months preceding the survey (AOR 0.71; 95% CI 0.63 to 0.80), having a
      normal maternal body mass index (18.5-24.99 kg/m(2)) (AOR 0.78; 95% CI 0.68 to
      0.89), being in the middle wealth quintile (AOR 0.83; 95% CI 0.71 to 0.98) or
      rich wealth quintile (AOR 0.83; 95% CI 0.70 to 0.98), having ever used family
      planning (AOR 0.68; 95% CI 0.57 to 0.80), having attended antenatal care (ANC)
      for the indexed pregnancy four times or more (AOR 0.73; 95% CI 0.59 to 0.91),
      having experienced time variation between the two surveys (AOR 0.73; 95% CI 0.64
      to 0.85), and breastfeeding for 2 years (AOR 0.76; 95% CI 0.66 to 0.87) were
      factors associated with lower odds of having anaemia in lactating mothers.
      CONCLUSIONS: Anaemia is highly prevalent among lactating mothers, particularly in
      the pastoralist communities of Somali and Afar. Promoting partner education,
      improving maternal nutritional status, and creating behavioural change to use
      family planning and ANC services at health facilities are recommended
      interventions to reduce the prevalence of anaemia among lactating mothers in
      Ethiopia.

PMID- 25872936
TI  - Evaluation of tumour vaccine immunotherapy for the treatment of advanced non
      small cell lung cancer: a systematic meta-analysis.
AB  - OBJECTIVES: Our meta-analysis performed a systematic evaluation on the
      therapeutic efficacy and safety of tumour vaccines for the treatment of advanced
      non-small cell lung cancer (NSCLC). DESIGN: Systematic review and meta-analysis
      of randomised controlled trials (RCT). DATA SOURCES: PubMed, the Cochrane Center
      Register of Controlled Trials, Science Direct and EMBASE were searched from
      January 1980 until January 2015. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: RCT
      were included; the control arm had to receive either placebo or chemotherapy or
      no treatment. MAIN OUTCOME MEASURES: The quality of the data from individual
      papers was assessed for overall survival (OS), clinical response rate and side
      effects. RESULTS: Overall, 11 RCT of advanced NSCLC with a total of 3986 patients
      were conducted for meta-analysis. The results showed that the vaccine arm
      significantly extended primary endpoint median overall survival compared with
      control group (p<0.00001) (HR 0.760; 95% CI 0.644 to 0.896; p=0.001). Three
      subgroup patients with tumour vaccine at 1-year, 2-year and 3-year survival rates
      also gained significant benefits compared with their corresponding control group
      (p=0.0004, 0.03 and 0.19, respectively). Besides, a significant improvement in
      median time to progression (TTP), median progression-free survival (PFS) and a
      trend of improvement in objective response rate were observed after tumour
      vaccine treatment (p=0.001, 0.005 and 0.05, respectively; median PFS HR 0.842;
      95% CI 0.744 to 0.954; p=0.007). A few severe adverse effects occurred in the
      tumour vaccine group, but fewer side effects were observed in the vaccine group
      compared with the control group (p<0.00001). CONCLUSIONS: Taken together, NSCLC
      tumour vaccines markedly prolong median OS (p<0.00001), median TTP (p=0.001) and
      median PFS (p=0.005), improve clinical response rate (p=0.05) and lessen adverse
      side effects (p<0.00001). Our meta-analysis suggests tumour vaccines improve the
      efficacy of the treatment, and also provide superiority in treatment of patients
      with advanced NSCLC among a variety of immunotherapy strategies.

PMID- 25872937
TI  - Validity of self-reported diabetes among middle-aged and older Chinese adults:
      the China Health and Retirement Longitudinal Study.
AB  - BACKGROUND: Self-reported diabetes has been found to be valid to evaluate
      people's diabetes status in the population of several countries. However, no such
      study has been conducted to assess the validity of self-reported diabetes in the
      Chinese population, the largest population with the highest rate of diabetes. The
      aim of our study is to evaluate the validity of self-reported diabetes among the
      middle-aged and older Chinese population. METHODS: Data from 11 601 participants,
      aged >=45, of the China Health and Retirement Longitudinal Study (CHARLS) during
      2011-2012, were analysed. Prevalent self-reported diabetes was compared with
      reference definition defined by fasting glucose, glycated haemoglobin and
      medication use. Sensitivity, specificity, positive predicted value, negative
      predicted value and kappa value were calculated overall, by 5-year age groups, by
      education levels and by living areas. RESULTS: The sensitivity of prevalent self
      reported diabetes was 41.5%, and the specificity was 98.6%. The sensitivity of
      self-reported diabetes increased with education levels, and was much higher among
      urban residents than rural residents (58.2% vs 35.0%). The specificity was above
      98% among all age groups, in different education levels, and in rural and urban
      areas. Self-reported diabetes had substantial agreement with reference definition
      among participants with above vocational school education or those living in
      urban areas (kappa=0.658 and 0.646, respectively). CONCLUSIONS: Although the
      sensitivity of self-reported diabetes was poor among middle-aged and older
      Chinese adults, the specificity and positive predictive values were fairly good.
      Furthermore, self-reported diabetes performed well among those with more than
      vocational school educations or those living in urban areas.

PMID- 25872938
TI  - Inner conflict in patients receiving oral anticancer agents: a qualitative study.
AB  - OBJECTIVES: To explore the experiences of patients receiving oral anticancer
      agents. DESIGN: A qualitative study using semistructured interviews with a
      grounded theory approach. SETTING: A university hospital in Japan. PARTICIPANTS:
      14 patients with gastric cancer who managed their cancer with oral anticancer
      agents. RESULTS: Patients with cancer experienced inner conflict between rational
      belief and emotional resistance to taking medication due to confrontation with
      cancer, doubt regarding efficacy and concerns over potential harm attached to use
      of the agent. Although they perceived themselves as being adherent to medication,
      they reported partial non-adherent behaviours. The patients reassessed their
      lives through the experience of inner conflict and, ultimately, they recognised
      their role in medication therapy. CONCLUSIONS: Patients with cancer experienced
      inner conflict, in which considerable emotional resistance to taking their
      medication affected their occasional non-adherent behaviours. In patient-centred
      care, it is imperative that healthcare providers understand patients' inner
      conflict and inconsistency between their subjective view and behaviour to support
      patient adherence.

PMID- 25872939
TI  - Usefulness of natriuretic peptide for the diagnosis of Kawasaki disease: a
      systematic review and meta-analysis.
AB  - OBJECTIVE: To examine the diagnostic value of serum B-type natriuretic peptide
      (BNP) in acute Kawasaki disease (KD). DESIGN: Systematic review and meta
      analysis. DATA SOURCES: A systematic literature search strategy was designed and
      carried out using MEDLINE, EMBASE and the Cochrane Library from inception to
      December 2013. We also performed manual screening of the bibliographies of
      primary studies and review articles, and contacted authors for additional data.
      STUDY ELIGIBILITY CRITERIA: We included all BNP and NT-pro (N-terminal
      prohormone) BNP assay studies that compared paediatric patients with KD to
      patients with febrile illness unrelated to KD. We excluded case reports, case
      series, review articles, editorials, congress abstracts, clinical guidelines and
      all studies that compared healthy controls. PRIMARY AND SECONDARY OUTCOME
      MEASURES: The performance characteristics of BNP were summarised using forest
      plots, hierarchical summary receiver operating characteristic (ROC) curves and
      bivariate random effects models. RESULTS: We found six eligible studies including
      279 cases of patients with KD and 203 febrile controls. Six studies examined NT
      proBNP and one examined BNP. In general, NT-proBNP is a specific and moderately
      sensitive test for identifying KD. The pooled sensitivity was 0.89 (95% CI 0.78
      to 0.95) and the pooled specificity was 0.72 (95% CI 0.58 to 0.82). The area
      under the summary ROC curve was 0.87 (95% CI 0.83 to 0.89). The positive
      likelihood ratio (LR+ 3.20, 95% CI 2.10 to 4.80) was sufficiently high to be
      qualified as a rule-in diagnostic tool in the context of high pre-test
      probability and compatible clinical symptoms. A high degree of heterogeneity was
      found using the Cochran Q statistic. CONCLUSIONS: Current evidence suggests that
      NT-proBNP may be used as a diagnostic tool for KD. NT-proBNP has high diagnostic
      value for identifying KD in patients with protracted undifferentiated febrile
      illness. Prospective large cohort studies are needed to help determine best cut
      off values and further clarify the role of NT-proBNP in the diagnosis process of
      KD.

PMID- 25872940
TI  - Use of the SONET score to evaluate Urgent Care Center overcrowding: a prospective
      pilot study.
AB  - OBJECTIVES: To derive a tool to determine Urgent Care Center (UCC) crowding and
      investigate the association between different levels of UCC overcrowding and
      negative patient care outcomes. DESIGN: Prospective pilot study. SETTING: Single
      centre study in the USA. PARTICIPANTS: 3565 patients who registered at UCC during
      the 21-day study period were included. Patients who had no overcrowding statuses
      estimated due to incomplete collection of operational variables at the time of
      registration were excluded in this study. 3139 patients were enrolled in the
      final data analysis. PRIMARY AND SECONDARY OUTCOME MEASURES: A crowding
      estimation tool (SONET: Severely overcrowded, Overcrowded and Not overcrowded
      Estimation Tool) was derived using the linear regression analysis. The average
      length of stay (LOS) in UCC patients and the number of left without being seen
      (LWBS) patients were calculated and compared under the three different levels of
      UCC crowding. RESULTS: Four independent operational variables could affect the
      UCC overcrowding score including the total number of patients, the number of
      results pending for patients, the number of patients in the waiting room and the
      longest time a patient was stationed in the waiting room. In addition, UCC
      overcrowding was associated with longer average LOS (not overcrowded: 133+/-76
      min, overcrowded: 169+/-79 min, and severely overcrowded: 196+/-87 min, p<0.001)
      and an increased number of LWBS patients (not overcrowded: 0.28+/-0.69 patients,
      overcrowded: 0.64+/-0.98, and severely overcrowded: 1.00+/-0.97). CONCLUSIONS:
      The overcrowding estimation tool (SONET) derived in this study might be used to
      determine different levels of crowding in a high volume UCC setting. It also
      showed that UCC overcrowding might be associated with negative patient care
      outcomes.

PMID- 25872941
TI  - ZEB1-associated drug resistance in cancer cells is reversed by the class I HDAC
      inhibitor mocetinostat.
AB  - Therapy resistance is a major clinical problem in cancer medicine and crucial for
      disease relapse and progression. Therefore, the clinical need to overcome it,
      particularly for aggressive tumors such as pancreatic cancer, is very high.
      Aberrant activation of an epithelial-mesenchymal transition (EMT) and an
      associated cancer stem cell phenotype are considered a major cause of therapy
      resistance. Particularly, the EMT-activator ZEB1 was shown to confer stemness and
      resistance. We applied a systematic, stepwise strategy to interfere with ZEB1
      function, aiming to overcome drug resistance. This led to the identification of
      both its target gene miR-203 as a major drug sensitizer and subsequently the
      class I HDAC inhibitor mocetinostat as epigenetic drug to interfere with ZEB1
      function, restore miR-203 expression, repress stemness properties, and induce
      sensitivity against chemotherapy. Thereby, mocetinostat turned out to be more
      effective than other HDAC inhibitors, such as SAHA, indicating the relevance of
      the screening strategy. Our data encourage the application of mechanism-based
      combinations of selected epigenetic drugs with standard chemotherapy for the
      rational treatment of aggressive solid tumors, such as pancreatic cancer. 

PMID- 25872942
TI  - A nonsense mutation of human XRCC4 is associated with adult-onset progressive
      encephalocardiomyopathy.
AB  - We studied two monozygotic twins, born to first cousins, affected by a
      multisystem disease. At birth, they both presented with bilateral cryptorchidism
      and malformations. Since early adulthood, they developed a slowly progressive
      neurological syndrome, with cerebellar and pyramidal signs, cognitive impairment,
      and depression. Dilating cardiomyopathy is also present in both. By whole-exome
      sequencing, we found a homozygous nucleotide change in XRCC4 (c.673C>T),
      predicted to introduce a premature stop codon (p.R225*). XRCC4 transcript levels
      were profoundly reduced, and the protein was undetectable in patients' skin
      fibroblasts. XRCC4 plays an important role in non-homologous end joining of DNA
      double-strand breaks (DSB), a system that is involved in repairing DNA damage
      from, for example, ionizing radiations. Gamma-irradiated mutant cells
      demonstrated reduction, but not abolition, of DSB repair. In contrast with
      embryonic lethality of the Xrcc4 KO mouse, nonsense mutations in human XRCC4 have
      recently been associated with primordial dwarfism and, in our cases, with adult
      onset neurological impairment, suggesting an important role for DNA repair in the
      brain. Surprisingly, neither immunodeficiency nor predisposition to malignancy
      was reported in these patients. 

PMID- 25872943
TI  - Osteopathic manipulative treatment and pain in preterms: study protocol for a
      randomised controlled trial.
AB  - BACKGROUND: Recent evidence proved the necessity to improve health care and pain
      management in newborns. Osteopathic manipulative treatment (OMT) has been largely
      used to treat painful syndromes as well as term and preterm newborns. Recent
      studies have demonstrated positive results of osteopathy in reducing length of
      stay and costs. However, no trials were carried out on pain in newborns. The aim
      of the present clinical trial is to explore the effectiveness of osteopathic
      treatment in reducing pain in a sample of preterms. METHODS/DESIGN: A three-armed
      single blinded placebo-control randomised controlled trial protocol has been
      designed to primarily evaluate the extent to which OMT is effective in reducing
      pain in preterms. One hundred and twenty newborns will be enrolled from one
      tertiary neonatal intensive care unit in central Italy and randomised in three
      groups: study, sham and control. The study group will be further prospectively
      randomised in two subgroups: experienced osteopaths and students. All preterms
      will receive standard medical care. Osteopathic treatment will be applied to the
      study group only whilst 'soft touch' will be administer to the sham group only.
      Newborns will undergo manual sessions once a week for the entire period of
      hospitalisation. Blinding will be assured for neonatal staff and outcome
      assessor. Primary outcome will be the mean difference in baseline score changes
      of PIPP questionnaire between discharge and entry among the three groups.
      Secondary outcomes will be: mean difference in length of stay and costs between
      groups. Statistical analyses will use per-protocol analysis method. Missing data
      will be handled using last observation carried forward imputation technique.
      DISCUSSION: The present single blinded randomised controlled trial has been
      designed to explore potential advantages of OMT in the management of newborns'
      pain. Currently, based on a patient-centred need-based approach, this research
      will be looking at the benefit of osteopathic care rather than the efficacy of a
      specific technique or a pre-determined protocol. TRIAL REGISTRATION: The protocol
      has been registered on ClinicalTrials.gov ( NCT02146677 ) on 20 May 2014.

PMID- 25872944
TI  - Virtual screening and synthesis of novel antitubercular agents through
      interaction-based pharmacophore and molecular docking studies.
AB  - Tuberculosis continues to become a major threat and wide spreading disease though
      out the world. Therefore it is required to identify the new drugs for the
      treatment of tuberculosis with better activity profile than the prevalent
      compounds. In present study we have screened and modified the antitubercular
      compounds from commercial chemical database using the interaction-based
      pharmacophore and molecular docking studies. In the first step different
      pharmacophores of cocrystal structures of enyol acyl carrier reductase (also
      known as InhA) proteins (2B36 and 3FNG) were generated and employed for screening
      of ChemDiv database. Four different pharmacophore hypothesis retrieved 3456 hits
      from approximately 0.67 million compounds. In the second filter, these hit
      molecules were subjected to the molecular docking studies in 2NSD and 3FNG
      crystal structures. On the basis of high fit values, GScore, structural diversity
      and visual inspection, one hundred compounds were selected, purchased and
      subjected to experimental validation for antitubercular activity against H37Rv
      Mycobacterium tuberculosis (MTB) strain. Three compounds showed the minimal
      inhibitory concentration (MIC) value at 16 MUg/mL and one compound VH04 showed
      the value at 1 MUg/mL. Then a more active amidoethylamine compound was developed
      by chemical modifications of the virtual hit VH04 against the MTB strain. We
      believe that this newly identified scaffold could be useful for the optimization
      of lead from hit compounds of new antitubercular agents.

PMID- 25872945
TI  - Development of a composite outcome score for a complex intervention - measuring
      the impact of Community Health Workers.
AB  - BACKGROUND: In health services research, composite scores to measure changes in
      health-seeking behaviour and uptake of services do not exist. We describe the
      rationale and analytical considerations for a composite primary outcome for
      primary care research. We simulate its use in a large hypothetical population and
      use it to calculate sample sizes. We apply it within the context of a proposed
      cluster randomised controlled trial (RCT) of a Community Health Worker (CHW)
      intervention. METHODS: We define the outcome as the proportion of the services
      (immunizations, screening tests, stop-smoking clinics) received by household
      members, of those that they were eligible to receive. First, we simulated a
      population household structure (by age and sex), based on household composition
      data from the 2011 England and Wales census. The ratio of eligible to received
      services was calculated for each simulated household based on published
      eligibility criteria and service uptake rates, and was used to calculate sample
      size scenarios for a cluster RCT of a CHW intervention. We assume varying
      intervention percentage effects and varying levels of clustering. RESULTS:
      Assuming no disease risk factor clustering at the household level, 11.7% of
      households in the hypothetical population of 20,000 households were eligible for
      no services, 26.4% for 1, 20.7% for 2, 15.3% for 3 and 25.8% for 4 or more. To
      demonstrate a small CHW intervention percentage effect (10% improvement in uptake
      of services out of those who would not otherwise have taken them up, and
      additionally assuming intra-class correlation of 0.01 between households served
      by different CHWs), around 4,000 households would be needed in each of the
      intervention and control arms. This equates to 40 CHWs (each servicing 100
      households) needed in the intervention arm. If the CHWs were more effective
      (20%), then only 170 households would be needed in each of the intervention and
      control arms. CONCLUSIONS: This is a useful first step towards a process-centred
      composite score of practical value in complex community-based interventions.
      Firstly, it is likely to result in increased statistical power compared with
      multiple outcomes. Second, it avoids over-emphasis of any single outcome from a
      complex intervention.

PMID- 25872947
TI  - Differences in Healing Patterns of the Bone-Implant Interface between Immediately
      and Delayed-Placed Titanium Implants in Mouse Maxillae.
AB  - BACKGROUND: There are no available data on the healing process at the bone
      implant interface after immediate implant placement. PURPOSE: This study aimed to
      establish an animal experimental model of titanium implants placed in mouse
      maxillae and compare the healing pattern of the bone-implant interface after
      immediate implant placement with that after delayed implant placement. MATERIALS
      AND METHODS: Maxillary first molars (M1) from 4-week-old mice were extracted and
      replaced with the implant following drilling (immediate-placement group). In
      contrast, M1 from 2-week-old mice were extracted, followed by drilling and
      implantation after 4 weeks (delayed-placement group). The decalcified samples at
      0-28 days after implantation were processed by immunohistochemistry, terminal
      deoxynucleotidyl transferase-mediated dUTP nick end labeling assay, and tartrate
      resistant acid phosphatase histochemistry. The elements and bone volume of
      undecalcified samples were quantitatively analyzed by an electron probe
      microanalyzer. RESULTS: Osseointegration was completed by 28 days after the
      procedure in both groups. There were no differences in contact area, bone loss at
      the cervical area, or rate of calcification at the bone-implant interface between
      the two groups. CONCLUSIONS: This study found no significant differences in the
      chronological healing process at the bone-implant interface between the two
      groups at the cellular level.

PMID- 25872946
TI  - C/EBP-Homologous Protein (CHOP) in Vascular Smooth Muscle Cells Regulates Their
      Proliferation in Aortic Explants and Atherosclerotic Lesions.
AB  - RATIONALE: Myeloid-derived C/EBP-homologous protein (CHOP), an effector of the
      endoplasmic reticulum stress-induced unfolded protein response, promotes
      macrophage apoptosis in advanced atherosclerosis, but the role of CHOP in
      vascular smooth muscle cells (VSMCs) in atherosclerosis is not known. OBJECTIVE:
      To investigate the role of CHOP in SM22alpha(+) VSMCs in atherosclerosis. METHODS
      AND RESULTS: Chop(fl/fl) mice were generated and crossed into the Apoe(-/-) and
      SM22alpha-CreKI(+) backgrounds. SM22alpha-CreKI causes deletion of floxed genes
      in adult SMCs. After 12 weeks of Western-type diet feeding, the content of alpha
      actin-positive cells in aortic root lesions was decreased in Chop(fl/fl)SM22alpha
      CreKI(+)Apoe(-/-) versus control Chop(fl/fl)Apoe(-/-) mice, and aortic explant
      derived VSMCs from the VSMC-CHOP-deficient mice displayed reduced proliferation.
      Kruppel-like factor 4 (KLF4), a key suppressor of VSMC proliferation, was
      increased in lesions and aortic VSMCs from Chop(fl/fl)SM22alpha-CreKI(+)Apoe(-/-)
      mice, and silencing Klf4 in CHOP-deficient VSMCs restored proliferation. CHOP
      deficiency in aortic VSMCs increased KLF4 through 2 mechanisms mediated by the
      endoplasmic reticulum stress effector activating transcription factor 4:
      transcriptional induction of Klf4 mRNA and decreased proteasomal degradation of
      KLF4 protein. CONCLUSIONS: These findings in SM22alpha-CHOP-deficient mice imply
      that CHOP expression in SM22alpha(+) VSMCs promotes cell proliferation by
      downregulating KLF4. The mechanisms involve newly discovered roles of CHOP in the
      transcriptional and post-translational regulation of KLF4.

PMID- 25872949
TI  - Quantum-Chemical Characterization of the Properties and Reactivities of Metal
      Organic Frameworks.

PMID- 25872948
TI  - Clinical manifestations, diagnosis, and treatment of hereditary angioedema:
      survey data from 94 physicians in Japan.
AB  - BACKGROUND: Hereditary angioedema (HAE) is a rare and potentially life
      threatening condition that results from mutations in the C1 inhibitor (C1-INH).
      Awareness of HAE among physicians in Japan is increasing, but real-world data are
      lacking. OBJECTIVE: To explore the clinical manifestations, diagnosis, quality of
      life (QOL), and treatment of Japanese patients with HAE. METHODS: A 14-point
      survey was developed and sent to 387 physicians in Japan (March to May 2014) to
      gather clinical data on their HAE patients' family history, severity and
      frequency of attacks, QOL, and therapy use. RESULTS: Data on 171 HAE patients
      were collected from 94 physicians (24.3% response rate). Of the patients, 76.6%
      had a family history of angioedema (AE), and 11.7% had experienced a death in the
      family due to an AE attack. HAE type I occurred in 99 patients (57.9%), HAE type
      II occurred in 9 patients (5.3%), HAE with normal C1-INH occurred in 3 patients
      (1.8%), and an additional 60 patients were unclassified. Mean time from initial
      symptoms to diagnosis was 13.8 years. Attacks that required airway management and
      abdominal surgery with uncertain diagnosis were observed in 9.5% and 2.9% of
      patients, respectively. In the past year, 21.0% of patients presented with more
      than 10 attacks, 21.1% were admitted to the hospital for more than 1 day, and
      28.7% were absent from work or school. On-demand C1-INH concentrate and
      prophylactic tranexamic acid were used in approximately half of the patients
      (47.4% and 39.2%, respectively). CONCLUSION: HAE is a severe condition
      characterized by recurrent AE attacks. In Japan, delayed patient diagnosis and
      limited use of HAE-specific therapies exacerbate the burden on HAE patients.

PMID- 25872950
TI  - A phase II study in advanced cancer patients to evaluate the early transition to
      palliative care (the PREPArE trial): protocol study for a randomized controlled
      trial.
AB  - BACKGROUND: Previous studies have demonstrated the benefit of early integration
      of palliative care (PC) in oncology. However, patients continue to receive late
      referrals to PC even in comprehensive cancer centers. Patients and health
      professionals may perceive PC as 'a place to die,' and this stigma is a barrier
      to timely referrals and to patient acceptance of treatment. METHODS/DESIGN: The
      primary objective is to evaluate the feasibility of psychosocial intervention and
      PC in patients with advanced cancer. The patients will be submitted to a series
      of brief psychosocial interventions that are based on cognitive behavioral
      therapy, and patient acceptance and satisfaction will be assessed. In addition,
      the impact of these interventions on depressive symptoms will be evaluated. A
      randomized, open-label, phase II trial with two intervention arms and a control
      group will be conducted. Patients who are started on palliative chemotherapy and
      who meet the inclusion criteria will be enrolled. The study participants will be
      recruited from the outpatient oncology clinics at Barretos Cancer Hospital and
      will be randomized into one of the following three treatment arms: Arm A, which
      will include five weekly psychosocial interventions based on CBT in combination
      with early PC; Arm B, which will include early PC only; and Arm C, which will
      include standard oncologic care. The Hospital Anxiety and Depression Scale
      (HADS), the Patient Health Questionnaire (PHQ-9), the Edmonton Symptom Assessment
      System (ESAS-br), the Family Satisfaction with End-of-Life Care (FAMCARE)-Patient
      scale, and the Disease Understanding Protocol will be used for data collection.
      The patients will answer these questionnaires at baseline and 45, 90, 120 and 180
      days after randomization. DISCUSSION: Despite evidence of the positive impact of
      early PC, it is often provided to patients only at later stages. The inadequate
      awareness and stigmatization of PC as a place to die are barriers that complicate
      the early referral. Patients with advanced cancer may benefit from a psychosocial
      and educational strategy that adequately prepares them for initial PC
      appointments after an early referral to PC. We anticipate that benefits of
      psychological intervention shall be synergistic to secondary emotional benefits
      from the early integration of PC. TRIAL REGISTRATION: This trial was registered
      on 6 May 2014 with ClinicalTrials.gov (identifier: NCT02133274).

PMID- 25872951
TI  - Hiatal hernias are correlated with increased severity of non-cystic fibrosis
      bronchiectasis.
AB  - BACKGROUND AND OBJECTIVE: Hiatal hernias (HH) are associated with gastro
      oesophageal reflux and may contribute to lung disease severity. We aimed to
      evaluate the prevalence of HH among stable non-cystic fibrosis bronchiectasis
      (NCFB) patients and determine associations with disease severity. METHODS: A
      retrospective cross-sectional cohort study of 100 consecutive NCFB patients in
      our institution was performed. Data were collected on baseline variables,
      microbiology, lung function and radiology, according to the modified Bhalla
      score. Disease severity was assessed using the Bronchiectasis Severity Index
      (BSI) and FACED severity scores. RESULTS: Following expert radiological review,
      81 patients were deemed suitable for study inclusion (mean age (SD) 62.6 (12.4),
      females 55 (67.9%), body mass index (BMI) 26.9 (5.7)); 29 (35.8%) were HH
      positive (HH+). HH+ patients had a trend towards higher BMI (P = 0.07), and a
      significantly higher proportion had reflux symptoms (HH+ 62.1% vs HH- 28.8%, P <
      0.01). The presence of HH+ was associated with cystic bronchiectasis (HH+ 30.1%,
      HH- 11.5%; P = 0.03), increased number of lobes involved (HH+ 2.62 (1.54), HH-
      2.17 (1.42); P = 0.03), increased extent of bronchiectasis, (HH+ 6.2 (4.7), HH-
      4.5 (3.1); P = 0.04), decreased parenchymal attenuation (HH+ 1.0 (1.8), HH- 0.2
      (0.5); P = 0.03) and reduced per cent predicted forced expiratory volume in 1 s
      (HH+ 75.4% (24.5), HH- 90.4% (25.5); P = 0.02). There was no lobar predilection.
      HH+ was associated with increased disease severity scores: BSI (HH+ 4.93 (1.65),
      HH- 3.25 (2.13); P < 0.001) and FACED (HH+ 2.21 (1.52), HH- 1.35 (1.43); P <
      0.01). CONCLUSIONS: HH+ was associated with worse disease severity in NCFB
      patients, characterized by decreased lung function, increased extent and severity
      of radiological disease, and increased composite disease severity scores.

PMID- 25872952
TI  - Young children with a positive reputation to maintain are less likely to cheat.
AB  - The present study examined whether having a positive reputation to maintain makes
      young children less likely to cheat. Cheating was assessed through a temptation
      resistance paradigm in which participants were instructed not to cheat in a
      guessing game. Across three studies (total N = 361), preschool-aged participants
      were randomly assigned to either a reputation condition, in which an experimenter
      told them that she had learned of their positive reputation from classmates, or
      to a control condition in which they received no such information. By age 5,
      children in the reputation condition cheated less often than those in the control
      condition even though nobody was watching and choosing not to cheat conflicted
      with their personal interest. These findings are the first to show that informing
      children that they have a positive reputation to maintain can influence their
      moral behavior. 

PMID- 25872953
TI  - Nutritional status, adiposity and asthma severity and control in children.
AB  - AIM: To investigate association between nutritional status, adiposity and asthma
      severity and control in children. METHODS: We conducted a case control study at
      two teaching hospitals in Brazil. Cases were children (3-12 years) with
      persistent asthma and age-matched controls were those with intermittent asthma.
      Nutritional status was assessed by body mass index (BMI). Adiposity was assessed
      by sum of skinfolds and waist circumference (WC). Crude and adjusted odds ratios
      (ORs) and 95% confidence intervals (95% CIs) were calculated using conditional
      logistic regression or multinomial logistic regression as appropriate. RESULTS:
      Two hundred sixty-eight cases and 126 controls were included. Obesity (>2 BMI z
      score for age) was significantly associated with persistent asthma (adjusted OR
      2.62; 95% CI 1.39-4.95). There was a significant linear relationship between BMI
      z-scores (<=1, >1 to <=2, >2) and risk of having persistent asthma (P = 0.003 for
      linear trend). Children with WC >90th percentile had a higher risk of persistent
      asthma when compared with those with WC <=90th percentile (adjusted OR 3.38; 95%
      CI 1.26-9.06). No significant difference was found in terms of nutritional status
      and adiposity between children whose asthma was controlled by inhaled
      corticosteroids and those requiring inhaled corticosteroids plus other
      medications for asthma control. CONCLUSIONS: Obesity measured by BMI and
      increased abdominal adiposity are significantly associated with risk of
      persistent asthma but not type of controller medications.

PMID- 25872954
TI  - Draconibacterium sediminis sp. nov., isolated from river sediment.
AB  - A Gram-reaction-negative, facultatively anaerobic and rod-shaped bacterium,
      designated strain JN14CK-3(T), was isolated from surface sediment of the Jiulong
      River of China and was characterized phenotypically and phylogenetically.
      Phylogenetic analysis of the 16S rRNA gene sequences indicated that strain JN14CK
      3(T) belonged to the genus Draconibacterium, with the highest sequence similarity
      (98.3%) to Draconibacterium orientale FH5(T). By contrast, strain JN14CK-3(T)
      shared low 16S rRNA gene sequence similarities ( < 91.0%) with other type
      strains. The sole respiratory quinone was MK-7. The polar lipids were
      phosphatidylethanolamine and several unidentified phospholipids and lipids. The
      major fatty acids were iso-C15:0, iso-C16:0, anteiso-C15:0, C17:0 2-OH, iso-C16:0
      3-OH and iso-C17:0 3-OH. The G + C content of the genomic DNA was 40.9 mol%. The
      digital DNA-DNA hybridization value and average nucleotide identity (ANI) between
      strain JN14CK-3(T) and D. orientale FH5(T) were 34.2 +/- 2.5% and 87.1%,
      respectively. The combined genotypic and phenotypic data showed that strain
      JN14CK-3(T) represents a novel species of the genus Draconibacterium, for which
      the name Draconibacteriumsediminis sp. nov. is proposed, with the type strain
      JN14CK-3(T) ( = MCCC 1A00734(T) = KCTC 42152(T)).

PMID- 25872955
TI  - Morphology and morphogenesis of a novel mangrove ciliate, Sterkiella subtropica
      sp. nov. (Protozoa, Ciliophora, Hypotrichia), with phylogenetic analyses based on
      small-subunit rDNA sequence data.
AB  - A novel marine hypotrichous ciliate, Sterkiella subtropica sp. nov., was recently
      isolated from a mangrove wetland in Hong Kong. Its morphology, morphogenesis and
      systematic position have been investigated. The novel species is diagnosed by
      combined features of morphology, ciliature and nuclear apparatus, while its
      ontogenetic events present a stable pattern: (i) the six streaks of the
      undulating membrane (UM) and cirral anlagen are segmented in a 1 : 3 : 3 : 3 : 4
      : 4 pattern from left to right, and form three frontal, four frontoventral, one
      buccal, five ventral and five transverse cirri; (ii) the dorsal structure is
      similar to most other oxytrichids; that is, in a '4+2' pattern with three caudal
      cirri being formed. Based on the small-subunit rDNA sequence, the novel species
      is different from its congeners by between 21 and 35 bp, with sequence identities
      from 0.978 to 0.987. All molecular trees exhibited a similar topology: the
      monophyly of species of the genus Sterkiella is not completely supported in our
      analyses, and approximately unbiased tests (both including and excluding the
      novel species) also reject the possibility that Sterkiella is a monophyletic
      lineage, as indicated by the morphology-based classification.

PMID- 25872956
TI  - Herbinix hemicellulosilytica gen. nov., sp. nov., a thermophilic cellulose
      degrading bacterium isolated from a thermophilic biogas reactor.
AB  - Phenotypic and phylogenetic studies were performed on new isolates of a novel
      Gram-stain-positive, anaerobic, non-sporulating, rod-shaped bacterium isolated
      from a thermophilic biogas plant. The novel organisms were able to degrade
      crystalline cellulose. 16S rRNA gene comparative sequence analysis demonstrated
      that the isolates formed a hitherto unknown subline within the family
      Lachnospiraceae. As a representative of the whole group of isolates, strain
      T3/55T was further characterized. The closest relative of T3/55T among the taxa
      with validly published names is Mobilitalea sibirica, sharing 93.9% 16S rRNA gene
      sequence similarity. Strain T3/55T was catalase-negative, indole-negative, and
      produced acetate, ethanol and propionic acid as major end products from cellulose
      metabolism. The major cellular fatty acids (>1%) were 16 : 0 dimethyl acetal, 16
      : 0 fatty acid methyl ester and 16 : 0 aldehyde. The DNA G+C content was 36.6
      mol%. A novel genus and species, Herbinix hemicellulosilytica gen. nov., sp.
      nov., is proposed based on phylogenetic analysis and physiological properties of
      the novel isolate. Strain T3/55T ( = DSM 29228T = CECT 8801T), represents the
      type strain of Herbinix hemicellulosilytica gen. nov., sp. nov.

PMID- 25872957
TI  - Phaeobacterium nitratireducens gen. nov., sp. nov., a phototrophic
      gammaproteobacterium isolated from a mangrove forest sediment sample.
AB  - A novel brown-coloured, Gram-negative-staining, rod-shaped, motile, phototrophic,
      purple sulfur bacterium, designated strain AK40T, was isolated in pure culture
      from a sediment sample collected from Coringa mangrove forest, India. Strain
      AK40T contained bacteriochlorophyll a and carotenoids of the rhodopin series as
      major photosynthetic pigments. Strain AK40T was able to grow
      photoheterotrophically and could utilize a number of organic substrates. It was
      unable to grow photoautotrophically and did not utilize sulfide or thiosulfate as
      electron donors. Thiamine and riboflavin were required for growth. The dominant
      fatty acids were C12 : 0, C16 : 0, C18 : 1omega7c and summed feature 3 (C16 :
      1omega7c and/or iso-C15 : 0 2-OH). The polar lipid profile of strain AK40T was
      found to contain diphosphatidylglycerol, phosphatidylethanolamine,
      phosphatidylglycerol and eight unidentified lipids. Q-10 was the predominant
      respiratory quinone. The DNA G+C content of strain AK40T was 65.5 mol%. 16S rRNA
      gene sequence comparisons indicated that the isolate represented a member of the
      family Chromatiaceae within the class Gammaproteobacteria. 16S rRNA gene sequence
      analysis indicated that strain AK40T was closely related to Phaeochromatium
      fluminis, with 95.2% pairwise sequence similarity to the type strain; sequence
      similarity to strains of other species of the family was 90.8-94.8%. Based on the
      sequence comparison data, strain AK40T was positioned distinctly outside the
      group formed by the genera Phaeochromatium, Marichromatium, Halochromatium,
      Thiohalocapsa, Rhabdochromatium and Thiorhodovibrio. Distinct morphological,
      physiological and genotypic differences from previously described taxa supported
      the classification of this isolate as a representative of a novel species in a
      new genus, for which the name Phaeobacterium nitratireducens gen. nov., sp. nov.
      is proposed. The type strain of Phaeobacterium nitratireducens is AK40T ( = JCM
      19219T = MTCC 11824T).

PMID- 25872958
TI  - Roseovarius antarcticus sp. nov., isolated from a decayed whale bone.
AB  - A pale yellow, ovoid- to rod-shaped and budding bacterium, designated strain M
      S13-148(T), was isolated from a decayed bone of whale from the eastern coast of
      King George Island, South Shetlands, Antarctica. Strain M-S13-148(T) exhibited
      motility, aerobic growth and was Gram-stain-negative. Strain M-S13-148(T) was
      positive for catalase and oxidase. Growth was observed at pH 6.0-9.0, at 4-42 
      degrees C and with 0-14% (w/v) NaCl. The novel strain contained
      diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine,
      phosphatidylethanolamine and an unknown phospholipid as the major polar lipids.
      The dominant cellular fatty acids were summed feature 8 (C18 : 1omega7c and/or
      C18 : 1omega6c), (58.8%) and C16 : 0 (11.7%). The respiratory quinone was Q-10
      and the DNA G + C content was 60.9 mol%. Neighbour-joining, maximum-likelihood
      and minimum-evolution phylogenetic trees, based on 16S rRNA gene sequences,
      indicated that strain M-S13-148(T) belonged to the genus Roseovarius and was most
      closely related to Roseovarius nanhaiticus CCTCC AB 208317(T) (93.72% 16S rRNA
      gene sequence similarity). The 16S rRNA gene sequence similarity with respect to
      members of the genus Roseovarius ranged from 91.81 to 93.94%. On the basis of
      phenotypic, molecular and chemotaxonomic characteristics, strain M-S13-148 is
      considered to represent a novel species of the genus Roseovarius, for which the
      name Roseovarius antarcticus sp. nov., is proposed. The type strain is M-S13
      148(T) ( = CCTCC AB2014072(T) = LMG 28420(T)).

PMID- 25872959
TI  - Phycicoccus soli sp. nov., isolated from soil.
AB  - A Gram-stain-positive, non-motile, coccus-shaped bacterium, strain THG-a14T, was
      isolated from soil of Gyeyang mountain in Incheon, Republic of Korea. The isolate
      grew optimally at 28  degrees C, at pH 6.5-7.5 and with 0-3 % (w/v) NaCl. Based
      on 16S rRNA gene sequence comparisons, strain THG-a14T was closely related to
      Phycicoccus aerophilus 5516T-20T (97.7 %), P. ginsenosidimutans BXN5-13T (97.6
      %), 'P. ochangensis' L1b-b9 (97.4 %) and P. bigeumensis MSL-03 (97.2 %). The DNA
      G+C content of strain THG-a14T was 71.6 mol%. In DNA-DNA hybridization, the DNA
      DNA relatedness between strain THG-a14T and its closest phylogenetically
      neighbours was below 50.0 %. Strain THG-a14T was characterized chemotaxonomically
      as having meso-diaminopimelic acid in the cell-wall peptidoglycan. Strain THG
      a14T contained glucose and ribose as whole-cell-wall sugars and menaquinone MK
      8(H4) as the major isoprenoid quinone. Polar lipids in strain THG-a14T consisted
      of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol,
      phosphoaminoglycolipids, unidentified phospholipids and unidentified lipids. The
      major fatty acids were iso-C16:0, iso-C15:0 and C17:1omega8c. On the basis of our
      polyphasic taxonomy study, strain THG-a14T represents a novel species within the
      genus Phycicoccus, for which the name Phycicoccussoli sp. nov. is proposed. The
      type strain is THG-a14T ( = KACC 17892T = JCM 19837T). 

PMID- 25872960
TI  - Burkholderia stagnalis sp. nov. and Burkholderia territorii sp. nov., two novel
      Burkholderia cepacia complex species from environmental and human sources.
AB  - Nine Burkholderia cepacia complex (Bcc) bacteria were isolated during
      environmental surveys for the ecological niche of Burkholderia pseudomallei, the
      aetiological agent of melioidosis, in the Northern Territory of Australia. They
      represented two multi-locus sequence analysis-based clusters, referred to as Bcc
      B and Bcc L. Three additional environmental and clinical Bcc B isolates were
      identified upon deposition of the sequences in the PubMLST database. Analysis of
      the concatenated nucleotide sequence divergence levels within both groups (1.4
      and 1.9%, respectively) and towards established Bcc species (4.0 and 3.9%,
      respectively) demonstrated that the two taxa represented novel Bcc species. All
      12 isolates were further characterized using 16S rRNA and recA gene sequence
      analysis, RAPD analysis, DNA base content determination, fatty acid methyl ester
      analysis and biochemical profiling. Analysis of recA gene sequences revealed a
      remarkable diversity within each of these taxa, but, together, the results
      supported the affiliation of the two taxa to the Bcc. Bcc B strains can be
      differentiated from most other Bcc members by the assimilation of maltose. Bcc L
      strains can be differentiated from other Bcc members by the absence of
      assimilation of N-acetylglucosamine. The names Burkholderia stagnalis sp. nov.
      with type strain LMG 28156(T) ( = CCUG 65686(T)) and Burkholderia territorii sp.
      nov. with type strain LMG 28158(T) ( = CCUG 65687(T)) are proposed for Bcc B and
      Bcc L bacteria, respectively.

PMID- 25872961
TI  - Application of multiplex ligation-dependent probe amplification, and
      identification of a heterozygous Alu-associated deletion and a uniparental disomy
      of chromosome 1 in two patients with 3-hydroxy-3-methylglutaryl-CoA lyase
      deficiency.
AB  - Mitochondrial 3-hydroxy-3-methylglutaryl-CoA lyase (HMGCL) deficiency is an
      autosomal recessive disorder affecting the leucine catabolic pathway and ketone
      body synthesis, and is clinically characterized by metabolic crises with
      hypoketotic hypoglycemia, metabolic acidosis and hyperammonemia. In the present
      study, we initially used PCR with genomic followed by direct sequencing to
      investigate the molecular genetic basis of HMGCL deficiency in two patients
      clinically diagnosed with the condition. Although we identified a mutation in
      each patient, the inheritance patterns of these mutations were not consistent
      with disease causation. Therefore, we investigated HMGCL using multiplex ligation
      dependent probe amplification (MLPA) to determine the copy numbers of all exons.
      A heterozygous deletion that included exons 2-4 was identified in one of the
      patients. MLPA revealed that the other patient had two copies for all HMGCL
      exons. Paternal uniparental isodisomy of chromosome 1 was confirmed in this
      patient by microarray analysis. These findings indicate that MLPA is useful for
      the identification of genomic aberrations and mutations other than small-scale
      nucleotide alterations. To the best of our knowledge, this is the first study
      describing HMGCL deficiency caused by uniparental disomy.

PMID- 25872962
TI  - Posttraumatic midshaft clavicular shortening does not result in relevant
      functional outcome changes.
AB  - BACKGROUND AND PURPOSE: Shoulder function may be changed after healing of a
      nonoperatively treated clavicular fracture, especially in cases of clavicular
      shortening or mal-union. We investigated scapular orientations and functional
      outcome in healed clavicular fractures with and without clavicular shortening.
      PATIENTS AND METHODS: 32 participants with a healed nonoperatively treated
      midshaft clavicular fracture were investigated. Motions of the thorax, arm, and
      shoulder were recorded by standardized electromagnetic 3D motion tracking. The
      DASH score and Constant-Murley score were used to evaluate functional outcome.
      Orientation of the scapula and humerus at rest and during standardized tasks, and
      strength and function of the affected shoulders were compared with corresponding
      values for the uninjured contralateral shoulders. RESULTS: Mean clavicular
      shortening was 25 mm (SD 16). Scapula protraction had increased by mean 4.4
      degrees  in rest position in the affected shoulders. During abduction, slightly
      more protraction, slightly more lateral rotation, and slightly less backward tilt
      was found for the affected shoulders. For anteflexion, the scapular orientations
      of the affected shoulders also showed slightly increased protraction, slightly
      increased lateral rotation, and slightly reduced backward tilt. Scapulohumeral
      kinematics, maximum humerus angles, and strength were not associated with the
      degree of clavicular shortening. All participants had excellent performance on
      the Constant-Murley score and DASH score. INTERPRETATION: Scapulohumeral
      kinematics in shoulders with a healed clavicular fracture differ from those in
      uninjured shoulders, but these changes are small, do not result in clinically
      relevant changes in outcome, and do not relate to the amount of clavicular
      shortening. These findings do not support routine operative reduction and
      fixation of shortened midshaft clavicular fractures based on the argument of
      functional outcome.

PMID- 25872963
TI  - Accuracy of predictive equations for estimating resting energy expenditure in
      obese adolescents.
AB  - OBJECTIVE: To compare resting energy expenditure (REE) measured by indirect
      calorimetry with REE predicted using different equations in obese adolescents.
      STUDY DESIGN: We recruited 264 obese patients (body mass index ranging from 30.0
      70.0 kg/m(2)) between 14 and 18 years of age. Data were obtained comparing
      measured and predicted REE derived from published equations for normal weight and
      obese adolescents. The average differences between measured and predicted REE, as
      well as the accuracy at +/- 10% level, were evaluated. RESULTS: Evaluating the
      mean REE in 109 males (1938 +/- 271 kcal/d) and 155 females (2569 +/- 459
      kcal/d), we found that the Lazzer equation in males had the smallest difference
      between measured and predicted REE; in females the Henry-1, Food and Agriculture
      Organization/World Health Organization/United Nations University, Schmelze, and
      Lazzer equations were the most accurate. The prediction accuracy was considered
      adequate within +/- 10%. CONCLUSIONS: REE predictive equations developed in obese
      patients and for specific age groups are more suitable than those for the general
      population. Inaccuracy of predicted REE could affect dietary prescription
      appropriateness and, consequently, dietary compliance in this age group.

PMID- 25872964
TI  - THE EFFECT OF ANGLE SLICE ACQUISITION ON COMPUTED TOMOGRAPHIC CERVICAL VERTEBRAL
      COLUMN MORPHOMETRY IN GREAT DANES.
AB  - Computed tomography (CT) scans can be acquired with the transverse images aligned
      either parallel to the endplates or perpendicular to the vertebral canal. The
      purpose of this prospective cross-sectional study was to determine the effect of
      angle acquisition on CT morphometric evaluation of the cervical vertebral column
      of Great Danes with and without cervical spondylomyelopathy. Twenty-eight Great
      Danes (13 normal, 15 affected) were sampled. For each dog, a set of CT images was
      acquired with the transverse slices aligned parallel to the endplates and another
      one with the transverse images aligned perpendicular to the vertebral canal. For
      each different set, transverse slices from the cranial, middle, and caudal
      aspects of the individual vertebral bodies C2-C7 were measured. Height, width,
      transverse area, right dorsal to left ventral height (RDLV), and left dorsal to
      right ventral height (LDRV) were recorded by a single observer at each location.
      For both affected and control dogs, significant differences between the
      measurements obtained from the two sets of transverse images were found only at
      the cranial aspect of the vertebrae (P = 0.005, P < 0.001, P < 0.001, P = 0.005,
      and P = 0.010 for height, width, area, RDLV, and LDRV, respectively).
      Measurements for the middle and caudal aspects did not differ. The funnel-shape
      morphology of the cervical vertebral foramina in Great Danes with stenosis of
      their cranial aspect may be responsible for the significant differences found.
      Considering that the morphometric parameters were significantly affected by CT
      slice angle in the current study, authors recommend that a standardized scanning
      protocol be followed when morphometric evaluations using CT are planned. 

PMID- 25872965
TI  - Analytical Performance Requirements for Systems for Self-Monitoring of Blood
      Glucose With Focus on System Accuracy: Relevant Differences Among ISO 15197:2003,
      ISO 15197:2013, and Current FDA Recommendations.
AB  - In the European Union (EU), the ISO (International Organization for
      Standardization) 15197 standard is applicable for the evaluation of systems for
      self-monitoring of blood glucose (SMBG) before the market approval. In 2013, a
      revised version of this standard was published. Relevant revisions in the
      analytical performance requirements are the inclusion of the evaluation of
      influence quantities, for example, hematocrit, and some changes in the testing
      procedures for measurement precision and system accuracy evaluation, for example,
      number of test strip lots. Regarding system accuracy evaluation, the most
      important change is the inclusion of more stringent accuracy criteria. In 2014,
      the Food and Drug Administration (FDA) in the United States published their own
      guidance document for the premarket evaluation of SMBG systems with even more
      stringent system accuracy criteria than stipulated by ISO 15197:2013. The
      establishment of strict accuracy criteria applicable for the premarket evaluation
      is a possible approach to further improve the measurement quality of SMBG
      systems. However, the system accuracy testing procedure is quite complex, and
      some critical aspects, for example, systematic measurement difference between the
      reference measurement procedure and a higher-order procedure, may potentially
      limit the apparent accuracy of a given system. Therefore, the implementation of a
      harmonized reference measurement procedure for which traceability to standards of
      higher order is verified through an unbroken, documented chain of calibrations is
      desirable. In addition, the establishment of regular and standardized post
      marketing evaluations of distributed test strip lots should be considered as an
      approach toward an improved measurement quality of available SMBG systems. 

PMID- 25872966
TI  - Trends in FDA regulation of software to control insulin dosing.

PMID- 25872967
TI  - System Accuracy Evaluation of Four Systems for Self-Monitoring of Blood Glucose
      Following ISO 15197 Using a Glucose Oxidase and a Hexokinase-Based Comparison
      Method.
AB  - BACKGROUND: The standard ISO (International Organization for Standardization)
      15197 is widely accepted for the accuracy evaluation of systems for self
      monitoring of blood glucose (SMBG). Accuracy evaluation was performed for 4 SMBG
      systems (Accu-Chek Aviva, ContourXT, GlucoCheck XL, GlucoMen LX PLUS) with 3 test
      strip lots each. To investigate a possible impact of the comparison method on
      system accuracy data, 2 different established methods were used. METHODS: The
      evaluation was performed in a standardized manner following test procedures
      described in ISO 15197:2003 (section 7.3). System accuracy was assessed by
      applying ISO 15197:2003 and in addition ISO 15197:2013 criteria (section 6.3.3).
      For each system, comparison measurements were performed with a glucose oxidase
      (YSI 2300 STAT Plus glucose analyzer) and a hexokinase (cobas c111) method.
      RESULTS: All 4 systems fulfilled the accuracy requirements of ISO 15197:2003 with
      the tested lots. More stringent accuracy criteria of ISO 15197:2013 were
      fulfilled by 3 systems (Accu-Chek Aviva, ContourXT, GlucoMen LX PLUS) when
      compared to the manufacturer's comparison method and by 2 systems (Accu-Chek
      Aviva, ContourXT) when compared to the alternative comparison method. All systems
      showed lot-to-lot variability to a certain degree; 2 systems (Accu-Chek Aviva,
      ContourXT), however, showed only minimal differences in relative bias between the
      3 evaluated lots. CONCLUSIONS: In this study, all 4 systems complied with the
      evaluated test strip lots with accuracy criteria of ISO 15197:2003. Applying ISO
      15197:2013 accuracy limits, differences in the accuracy of the tested systems
      were observed, also demonstrating that the applied comparison method/system and
      the lot-to-lot variability can have a decisive influence on accuracy data
      obtained for a SMBG system.

PMID- 25872968
TI  - Rhodium-catalyzed annulation between 2-arylimidazo[1,2-a]pyridines and alkynes
      leading to pyrido[1,2-a]benzimidazole derivatives.
AB  - A rhodium-catalyzed annulation between 2-arylimidazo[1,2-a]pyridines and alkynes
      was developed, leading to pyrido[1,2-a]benzimidazole derivatives in moderate to
      excellent yields. Notably, the ring C in pyrido[1,2-a]benzimidazole and the
      naphthalene framework were constructed consecutively, which provided a potential
      pathway leading to such a structure. This procedure tolerated chloro, bromo,
      cyano and methoxycarbonyl groups. 

PMID- 25872969
TI  - Are Interprofessional Roundtable Debriefings Useful in Decreasing ED Fall Rates?
      Findings From a Quality-Improvement Project.
AB  - There are more than 1 million patient falls each year in the United States. Falls
      are known to be a sign of poor health, are a marker of decline in function, and
      are associated with high morbidity. The objective of this study was to determine
      the effectiveness of a Falls Roundtable intervention for reducing the rates of
      patient falls in an urban academic trauma center emergency department. METHODS:
      We implemented a Falls Roundtable performance-improvement debriefing intervention
      in a single urban academic emergency department. To evaluate this intervention,
      we conducted a retrospective analysis of patient fall events 13 months before and
      14 months after implementation. We evaluated pre- and post-intervention
      differences in the total number of assisted falls, unassisted falls, and rate of
      falls. RESULTS: Despite a slowly improving trend in falls after the intervention,
      there was no statistically significant improvement in the number of assisted
      falls, number of unassisted falls, or rate of falls. The Falls Roundtable
      intervention was helpful in identifying many additional actionable improvement
      opportunities in the emergency department. IMPLICATIONS FOR PRACTICE: The Falls
      Roundtable incident debriefing intervention alone does not appear to be an
      effective tool for falls prevention in the ED setting but may serve as an
      integral component of a multifaceted fall-reduction strategy.

PMID- 25872970
TI  - Emergency Department Placement and Management of Indwelling Urinary Catheters in
      Older Adults: Knowledge, Attitudes, and Practice.
AB  - Indwelling urinary catheters (IUCs) are placed frequently in older adults in the
      emergency department (ED). Though often a critical intervention, IUCs carry
      significant risks. Our objective was to examine current knowledge, attitudes, and
      practice of emergency nurses and other providers regarding IUC placement and
      management in older adults. METHODS: We surveyed ED providers at a large, urban,
      academic medical center. We developed questionnaires using items from previously
      validated instruments and questions created for this study. We also assessed
      providers' management of 25 unique clinical scenarios, each representing an
      established appropriate or inappropriate indication for IUC placement. RESULTS:
      129 ED providers participated: 43 nurses and 86 other providers. Ninety-one
      percent of nurses and 87% of other providers reported comfort with appropriate
      indications for IUC placement. Despite this, on the clinical vignettes, nurses
      correctly identified the appropriate approach for IUC placement in only 40% of
      cases and other providers in only 37%. Practice varied widely between individual
      providers, with the nurse participants reporting appropriate practice in 16%-64%
      of clinical scenarios and other providers in 8%-68%. Few nurses or other
      providers reported reassessing their patients for IUC removal at transfer to the
      hospital (28% of nurses and 7% of other providers), admission (24% and 14%), or
      shift change (14% and 8%). DISCUSSION: Although emergency nurses and other
      providers report comfort with appropriate indications for IUC placement, reported
      practice patterns showed inconsistencies with established guidelines. Wide
      practice variation exists between individual providers. Moreover, nurses and
      other providers infrequently consider IUC removal after placement.

PMID- 25872971
TI  - The role of solvent heterogeneity in determining the dispersion interaction
      between nanoassemblies.
AB  - Understanding fundamental nanoassembly processes on intermediate scales between
      molecular and continuum scales requires an in-depth analysis of the coupling
      between particle interactions and molecular details. This is because the discrete
      nature of the solvent becomes comparable to the characteristic length scales of
      assembly. Utilizing the spatial density response of a solvent to a surface in
      conjunction with the Clausius-Mossotti equation, we present a simple theory
      relating the discrete nature of solvent to dispersion interactions. Our study
      reveals that dispersion interactions are indeed sensitive to the spatial
      variation of solvent density, manifesting in dramatic deviations in van der Waals
      forces from the conventional formulation (e.g., with uniform solvent density).
      This study provides the first steps toward relating molecular scale principles,
      namely the detailed nature of solvent response to an interface, to the underlying
      hydration forces between surfaces. 

PMID- 25872972
TI  - Differential skeletal impact of tenofovir disoproxil fumarate in young versus old
      HIV-infected adults.
AB  - BACKGROUND: Lower peak bone mass in early adulthood predicts subsequent fragility
      fractures. Antiretroviral toxicity could contribute to young HIV-infected
      individuals not achieving adequate peak bone mass. OBJECTIVE: To determine if
      tenofovir disoproxil fumarate's (TDF) effect on bone mineral density (BMD)
      differs by age. METHODS: We examined BMD data at the lumbar spine and hip from
      AIDS Clinical Trials Group (ACTG) A5224s and ASSERT and randomized treatment
      naive studies comparing TDF/emtricitabine versus abacavir/lamivudine (with
      efavirenz or atazanavir/ritonavir). In this post hoc analysis, we defined the TDF
      effect as the difference between mean 48-week BMD per cent changes for lumbar
      spine and hip in individuals randomized to TDF versus abacavir. We used
      multivariable linear regression to compare the TDF effect in individuals younger
      and older than 30 years. If TDF effect by age did not differ significantly
      between studies, we pooled study populations. Otherwise, analyses were conducted
      separately within each study population. RESULTS: Among 652 subjects, 21% were
      below age 30 years. The relationship between age and TDF effect significantly
      differed between A5224s and ASSERT (P = 0.008 for lumbar spine; P = 0.007 for
      hip). In A5224s, there was more bone loss with TDF at lumbar spine and hip in
      subjects under 30 years old versus in older subjects ( - 4.5% vs - 1.4%; P =
      0.045; - 4.3% vs - 1.6%; P = 0.026, respectively). There was no significant
      evidence for this age-associated TDF effect in ASSERT. CONCLUSIONS: There was
      heterogeneity in the observed effect of TDF on bone density in young adults
      compared to older adults, suggesting that further investigation is required to
      understand the impact of age on BMD decline with TDF.

PMID- 25872973
TI  - Characteristics of patients with false- ST-segment elevation myocardial
      infarction diagnoses.
AB  - BACKGROUND: A subgroup of patients presenting with suspected ST-elevation
      myocardial infarction (STEMI) have no culprit lesion during coronary angiography
      (false-positive STEMI). Little is known about patient- and system-related factors
      that are associated with false-positive STEMI. We evaluated the incidence,
      correlates, delay, final diagnosis, and outcome of patients with false-positive
      STEMI. METHODS: We studied 827 consecutive patients presenting with suspected
      STEMI between January 2011-September 2012. RESULTS: A false positive STEMI
      activation was identified in 68 patients (8.2%). Patients with false-positive
      STEMI were younger (57 vs 63 year; p=0.020), less often had hypercholesterolemia
      (19 vs 43%; p=0.001), and had a higher heart rate (82 vs 75 bpm; p=0.014). The
      association between these factors and false-positive STEMI activation persisted
      in multivariate analysis. The duration of symptoms to call was longer in false
      positive STEMI patients (128 vs 83 min; p=0.030), although this did not reach
      statistical significance in multivariate analysis. Final diagnosis in patients
      with false-positive STEMI activation was particularly from unknown origin (41%).
      There were no significant differences in mortality at 30 days and one year
      between patients with STEMI and false-positive STEMI. CONCLUSION: The incidence
      of false-positive STEMI was 8.2% in patients suspected of STEMI. Patients with
      false-positive STEMI differ from STEMI patients in certain baseline
      characteristics and in patient delay. Interestingly, absence of coronary disease
      did not translate into better clinical outcome.

PMID- 25872974
TI  - A tetranuclear copper cluster-based MOF with sulfonate-carboxylate ligands
      exhibiting high proton conduction properties.
AB  - A tetranuclear copper cluster-based MOF with sulfonate-carboxylate ligands has
      been synthesized. It possesses one-dimensional irregular channels lined with
      sulfonate, carboxylate, and DMF molecules, which show a high proton conductivity
      of 7.4 * 10(-4) S cm(-1) at 95  degrees C and 95% relative humidity. 

PMID- 25872975
TI  - Adaptations to a diet-based weight-reducing programme in obese women resistant to
      weight loss.
AB  - The aim of this study was to assess energy intake, resting metabolic rate (RMR),
      appetite sensations, eating behaviours and sleep duration and quality in obese
      women resistant to body weight loss when subjected to a diet-based weight
      reducing programme. A pooled cohort of obese women (n = 75; aged 39 +/- 8 years;
      body mass index: 33 +/- 4 kg m(-2)) participated in a 12-16-week diet-based
      weight loss programme targeting a daily energy deficit of 500-700 kcal d(-1).
      Women were classified in tertiles a posteriori based on the response of their
      body weight to dietary supervision (high, moderate and low responders). Post
      intervention, mean weight loss was 3.3 +/- 2.8 kg and explained by the 2.9 +/-
      2.6 kg reduction in fat mass. Mean weight loss was 6.2 +/- 1.6, 3.4 +/- 0.6 and
      0.2 +/- 1.4 kg in participants classified in the high, middle and low tertiles,
      respectively. Women in the low tertile reduced their daily energy intake and
      susceptibility to hunger during the programme to a lesser extent than those in
      the high tertile and had higher fasting hunger in response to the dietary
      intervention. Women in the high tertile maintained their RMR, which was in
      contrast to the significant decrease predicted by their weight loss. They also
      reported a significant improvement in sleep quality and an increase in sleep
      duration compared with other tertiles. The differences in the response of body
      weight to dietary supervision may be explained, in part, by variations in energy
      intake, eating behaviours, appetite sensations and sleep duration and quality.

PMID- 25872976
TI  - High Relapse Rates Despite Early Intervention with Intravenous Methylprednisolone
      Pulse Therapy for Severe Childhood Alopecia Areata.
AB  - BACKGROUND: Previous data suggest that early application of intravenous
      methylprednisolone pulse therapy (IV-MPPT) may improve the disease course of
      alopecia areata. The objective of this study was to investigate the outcome of IV
      MPPT in severe childhood alopecia areata, predominantly with short disease
      duration. METHODS: Eighteen children (10 girls, 8 boys) younger than 17 years old
      (median age 7.7 yrs, range 2.1-16.5 yrs) treated with IV-MPPT for severe
      childhood alopecia areata in a referral center for pediatric dermatology over 3
      years (median disease duration 4 mos, range 1-12 mos) were retrospectively
      evaluated. Five patients had alopecia areata totalis or universalis and 13 had
      alopecia multilocularis. The median scalp area affected by alopecia was 60%
      (range 30%-100%). All patients underwent two or three cycles of IV-MPPT at
      monthly intervals (maximum 500 mg/day on three consecutive days). RESULTS: Within
      7 months after the last IV-MPPT session, 10 of 18 children had good response
      (>=75% of hair regrowth), with eight showing improvement within the first 4
      months. Of the remaining eight patients, one had moderate response (50%-74%
      regrowth), three had poor response (1%-49% regrowth), and four (all with alopecia
      areata universalis or totalis) had no response. Seven of the initial 10 good
      responders experienced relapses, with marked hair loss after the last IV-MPPT
      session. The estimated median time to relapse was 8 months (95% confidence
      interval 7, 9 mos). CONCLUSION: IV-MPPT, even early in the course of disease, did
      not affect long-term outcome of alopecia areata in our group of severely affected
      patients.

PMID- 25872979
TI  - Automated growth of metal-organic framework coatings on flow-through functional
      supports.
AB  - A fully automated method for the controlled growth of metal-organic framework
      coatings on flow-through functional supports is reported. The obtained hybrid
      flow-through supports show high performance for the automated extraction of water
      pollutants. 

PMID- 25872977
TI  - Severing corneal nerves in one eye induces sympathetic loss of immune privilege
      and promotes rejection of future corneal allografts placed in either eye.
AB  - Less than 10% of corneal allografts undergo rejection even though HLA matching is
      not performed. However, second corneal transplants experience a threefold
      increase in rejection, which is not due to prior sensitization to
      histocompatibility antigens shared by the first and second transplants since
      corneal grafts are selected at random without histocompatibility matching. Using
      a mouse model of penetrating keratoplasty, we found that 50% of the initial
      corneal transplants survived, yet 100% of the subsequent corneal allografts
      (unrelated to the first graft) placed in the opposite eye underwent rejection.
      The severing of corneal nerves that occurs during surgery induced substance P
      (SP) secretion in both eyes, which disabled T regulatory cells that are required
      for allograft survival. Administration of an SP antagonist restored immune
      privilege and promoted graft survival. Thus, corneal surgery produces a
      sympathetic response that permanently abolishes immune privilege of subsequent
      corneal allografts, even those placed in the opposite eye and expressing a
      completely different array of foreign histocompatibility antigens from the first
      corneal graft. 

PMID- 25872980
TI  - TR-FRET binding assay targeting unactivated form of Bruton's tyrosine kinase.
AB  - Bruton's Tyrosine Kinase (BTK) is one of the crucial kinases for the B cell
      maturation and mast cell activation, and specific inhibitors of BTK are
      considered to be attractive targets in drug discovery research. In this Letter,
      we have designed and synthesized a new fluorescent probe for TR-FRET-based high
      throughput screening, to identify compounds that preferentially bind to an
      inactive conformation of BTK which has a unique structural feature. A set of
      kinase-focused compound library was screened using this assay method, and
      compound 31 was successfully identified as a potent inhibitor which
      preferentially bind to the inactive conformation of BTK. These results suggest
      that this screening method has a great potential for the discovery of novel
      selective BTK inhibitors. 

PMID- 25872978
TI  - Comparative effectiveness of gemcitabine plus cisplatin versus methotrexate,
      vinblastine, doxorubicin, plus cisplatin as neoadjuvant therapy for muscle
      invasive bladder cancer.
AB  - BACKGROUND: Gemcitabine plus cisplatin (GC) has been adopted as a neoadjuvant
      regimen for muscle-invasive bladder cancer despite the lack of Level I evidence
      in this setting. METHODS: Data were collected using an electronic data-capture
      platform from 28 international centers. Eligible patients had clinical T
      classification 2 (cT2) through cT4aN0M0 urothelial cancer of the bladder and
      received neoadjuvant GC or methotrexate, vinblastine, doxorubicin, plus cisplatin
      (MVAC) before undergoing cystectomy. Logistic regression was used to compute
      propensity scores as the predicted probabilities of patients being assigned to
      MVAC versus GC given their baseline characteristics. These propensity scores were
      then included in a new logistic regression model to estimate an adjusted odds
      ratio comparing the odds of attaining a pathologic complete response (pCR)
      between patients who received MVAC and those who received GC. RESULTS: In total,
      212 patients (146 patients in the GC cohort and 66 patients in the MVAC cohort)
      met criteria for inclusion in the analysis. The majority of patients in the MVAC
      cohort (77%) received dose-dense MVAC. The median age of patients was 63 years,
      they were predominantly men (74%), and they received a median of 3 cycles of
      neoadjuvant chemotherapy. The pCR rate was 29% in the MVAC cohort and 31% in the
      GC cohort. There was no significant difference in the pCR rate when adjusted for
      propensity scores between the 2 regimens (odds ratio, 0.91; 95% confidence
      interval, 0.48-1.72; P = .77). In an exploratory analysis evaluating survival,
      the hazard ratio comparing hazard rates for MVAC versus GC adjusted for
      propensity scores was not statistically significant (hazard ratio, 0.78; 95%
      confidence interval, 0.40-1.54; P = .48). CONCLUSIONS: Patients who received
      neoadjuvant GC and MVAC achieved comparable pCR rates in the current analysis,
      providing evidence to support what has become routine practice.

PMID- 25872981
TI  - Syntheses of natural 1,3-polyol/alpha-pyrone and its all stereoisomers to
      estimate antifungal activities against plant pathogenic fungi.
AB  - All stereoisomers of 1,3-polyol/alpha-pyrone 1-8 with more than 99% ee were
      synthesized to estimate the effect of stereochemistry on the antifungal activity.
      The absolute configuration of natural compound was determined as (6R,2'S,4'R)-2.
      The eight stereoisomers showed the antifungal activity against plant pathogenic
      Alternaria alternata Japanese pear pathotype and Colletotrichum lagenarium. The
      large difference of activity level was not observed between stereoisomers,
      showing 43-72% of growth ratio against control at 0.5mM. The most potent
      stereoisomer was (6S,2'S,4'S)-8 and the activity of (6R,2'S,4'S)-1 was weakest
      against both fungi. 

PMID- 25872982
TI  - Application of cultured human mast cells (CHMC) for the design and structure
      activity relationship of IgE-mediated mast cell activation inhibitors.
AB  - Here we report the optimization of small molecule inhibitors of human mast cell
      degranulation via anti-IgE-mediated tryptase release following cross-linking and
      activation of IgE-loaded FcepsilonR1 receptors. The compounds are selective
      upstream inhibitors of FcepsilonR1-dependent human mast cell degranulation and
      proved to be devoid of activity in downstream ionomycin mediated degranulation.
      Structure-activity relationship (SAR) leading to compound 26 is outlined. 

PMID- 25872983
TI  - Design and synthesis of novel 1,2-dithiolan-4-yl benzoate derivatives as PTP1B
      inhibitors.
AB  - A series of novel 1,2-dithiolan-4-yl benzoate compounds were synthesized and
      evaluated for in vitro PTP1B inhibitory activity. Some derivatives exhibited
      improved PTP1B inhibitory activity and selectivity compared to hit 6a, a compound
      from in-house library screening inspired by marine cyclic disulfide. The
      preliminary SAR analysis with assistance of molecular modeling approach revealed
      6j (IC50=0.59MUM) as the most potent PTP1B inhibitor among all derivatives. 

PMID- 25872984
TI  - Synthesis and activities towards resistant cancer cells of sulfone and sulfoxide
      griseofulvin derivatives.
AB  - Griseofulvin, an antifungal drug, has been shown in recent years to have anti
      proliferative activities. We report here the synthesis of new analogs of
      griseofulvin, substituted in 2' by a sulfonyl group or in 3' by a sulfinyl or
      sulfonyl group. These compounds exhibit good anti-proliferative activities
      against SCC114 cells, an oral squamous carcinoma cell line showing pronounced
      centrosome amplification, and unexpected cytotoxic activities on HCC1937 cells, a
      triple negative breast cancer cell line resistant to microtubule inhibitors. 

PMID- 25872985
TI  - Synthesis of benzoxazole derivatives of honokiol as insecticidal agents against
      Mythimna separata Walker.
AB  - A series of novel benzoxazole compounds derived from a naturally occurring
      neolignan honokiol were prepared. Their insecticidal activity was tested against
      the pre-third-instar larvae of oriental armyworm (Mythimna separata Walker) in
      vivo. Most of the tested derivatives exhibited more potential insecticidal
      activity than their precursor honokiol at the concentration of 1mg/mL. Especially
      compound 6e, containing 4-acetyloxyphenyl groups at the C8 and C8' positions,
      displayed the most potent insecticidal activity with the final mortality rate of
      62.1%. 

PMID- 25872986
TI  - Screening for an ivermectin slow-release formulation suitable for malaria vector
      control.
AB  - BACKGROUND: The prospect of eliminating malaria is challenged by emerging
      insecticide resistance and vectors with outdoor and/or crepuscular activity.
      Ivermectin can simultaneously tackle these issues by killing mosquitoes feeding
      on treated animals and humans. A single oral dose, however, confers only short
      lived mosquitocidal plasma levels. METHODS: Three different slow-release
      formulations of ivermectin were screened for their capacity to sustain mosquito
      killing levels of ivermectin for months. Thirty rabbits received a dose of one,
      two or three silicone implants containing different proportions of ivermectin,
      deoxycholate and sucrose. Animals were checked for toxicity and ivermectin was
      quantified periodically in blood. Potential impact of corresponding long-lasting
      formulation was mathematically modelled. RESULTS: All combinations of formulation
      and dose released ivermectin for more than 12 weeks; four combinations sustained
      plasma levels capable of killing 50% of Anopheles gambiae feeding on a treated
      subject for up to 24 weeks. No major adverse effects attributable to the drug
      were found. Modelling predicts a 98% reduction in infectious vector density by
      using an ivermectin formulation with a 12-week duration. CONCLUSIONS: These
      results indicate that relatively stable mosquitocidal plasma levels of ivermectin
      can be safely sustained in rabbits for up to six months using a silicone-based
      subcutaneous formulation. Modifying the formulation of ivermectin promises to be
      a suitable strategy for malaria vector control.

PMID- 25872987
TI  - New and treatment-relevant risk stratification for thrombosis in essential
      thrombocythemia and polycythemia vera.

PMID- 25872988
TI  - Three-dimensional honeycomb-like networks of birnessite manganese oxide assembled
      by ultrathin two-dimensional nanosheets with enhanced Li-ion battery
      performances.
AB  - Three-dimensional (3D) honeycomb-like birnessite networks composed of ultrathin
      two-dimensional (2D) nanosheets were firstly synthesized through a facile and low
      cost synthetic route. By using carbon microspheres as a template instead of
      graphene, hierarchical birnessite structures assembled by ultrathin nanosheets
      including york-shell and hollow structures were obtained besides the ultrathin
      birnessite nanosheets with a thickness of about 0.7 nm. By assembling carbon
      spheres into an ordered 3D array, novel 3D honeycomb-like birnessite structures
      assembled by ultrathin nanosheets were firstly prepared. When evaluated as an
      anode material for Li-ion batteries, the 3D honeycomb-like networks show enhanced
      electrochemical performances with high capacities, excellent cycling stability
      and good rate capability, which can be ascribed to the novel 3D honeycomb-like
      macroporous structure with a 3D inverse opal structure, well-ordered macropores,
      interconnected walls and a regular periodicity. 

PMID- 25872989
TI  - [Macrolide resistance in Treponema pallidum subsp. pallidum in the Czech Republic
      and in other countries].
AB  - Treponema pallidum subsp. pallidum (TPA) is the causative agent of the sexually
      transmitted disease syphilis. In the Czech Republic, several hundred cases of
      syphilis are reported annually; e.g. in 2012, 696 syphilis cases were documented.
      In the last decades, an increasing prevalence of macrolide resistant TPA strains
      harboring A2058G or A2059G mutations in the 23S rRNA gene has been reported.
      Macrolides were used (and rarely are still being used) in the Czech Republic for
      the treatment of syphilis in patients allergic to penicillin. While 37% of TPA
      strains were resistant to macrolides between 2004 and 2010, this rate increased
      to 67% between 2011-2013. High prevalence of A2058G or A2059G mutations and
      increasing rates of macrolide resistant TPA strains have also been documented in
      other developed countries. Therefore, macrolides should not be used in the
      treatment of syphilis.

PMID- 25872990
TI  - Minimum inhibitory concentrations of erythromycin and other antibiotics for Czech
      strains of Bordetella pertussis.
AB  - AIM OF THE STUDY: To test the susceptibility to first-line and alternative
      antibiotics of 70 Bordetella pertussis (B. pertussis) strains recovered from
      patients with whooping cough through national pertussis surveillance in the Czech
      Republic (CR) in 1967-2010. MATERIAL AND METHODS: The minimum inhibitory
      concentrations (MICs) of erythromycin, clarithromycin, azithromycin,
      ciprofloxacin, and co-trimoxazole were tested by the reference agar dilution
      method on Bordet-Gengou agar with 15 % defibrinated sheep blood. RESULTS: Each of
      the 70 study strains was inhibited by two concentrations of erythromycin and
      azithromycin (0.06 and 0.12 mg/l) and by three concentrations of clarithromycin
      (0.03, 0.06, and 0.12 mg/l), with the highest concentration of the MIC range
      being 0.12 mg/l for all these similar antibiotics. Tested in a 2-fold geometric
      dilution series, the concentration of erythromycin required to inhibit 90 % of
      the study strains (MIC90) was one dilution step lower (0.06 mg/l) than those of
      clarithromycin and azithromycin (0.12 mg/l). All study strains were inhibited by
      a single concentration of ciprofloxacin (0.06 mg/l) and two concentrations of co
      trimoxazole (0.12 and 0.25 mg/l). CONCLUSION: The panel of 70 Czech strains of B.
      pertussis appears to be homogeneous in terms of the MICs of the antibiotics
      tested, with two to three low concentrations being effective against all strains.
      To be inhibited, no strain required a higher concentration of erythromycin,
      clarithromycin, azithromycin, ciprofloxacin, or co-trimoxazole.

PMID- 25872991
TI  - [Contribution of the detection of IgA antibodies to the laboratory diagnosis of
      mumps in the population with a high vaccination coverage].
AB  - STUDY OBJECTIVE: Serological diagnosis of epidemic mumps can be difficult in
      vaccinated persons, particularly due to the absence of specific IgM antibodies.
      The aim was to find whether adding the detection of IgA antibodies to the
      currently used routine serological diagnosis of mumps (detection of IgM and IgG
      antibodies in an acute serum sample) would make the serological diagnosis of
      mumps more effective in a population with a high vaccination coverage. At the
      same time, ELISA kits for the detection of early IgA and IgM antibodies against
      the mumps virus were compared and statistical analysis of the results was
      performed. MATERIAL AND METHODS: Sixty-four acute sera from patients with
      laboratory confirmed diagnosis of mumps were included in the study. Clinical
      specimens were collected at the onset of clinical symptoms. To test the sera, the
      MASTAZYME ELISA Mumps IgA kit (MAST DIAGNOSTICA, Germany) with the MASTSORB
      sorbent (RF and IgG) and Enzygnost Anti-Parotitis-Virus/IgM kit (Siemens,
      Germany) were used. A panel of 121 acute sera with no epidemiological link to
      mumps virus served as specificity controls for the IgA assay. The epidemiological
      data were derived from the EPIDAT system. The level of agreement was assessed
      using the McNemara test and Cohen's coefficient kappa. The Stata 9.2 software
      (Stata Corp LP, College Station, USA) was used for statistical analysis. RESULTS:
      The detection of IgA and IgM antibodies against the mumps virus yielded
      concordant results in 50/64 acute sera, 32 positive and 18 negative, i.e. an
      agreement of 78.12 %. Of the remaining 14 samples, 13 were only IgA positive and
      one was only IgM positive. The controls showed non-specific IgA positivity in
      5/121 samples which indicates a 96% specificity. CONCLUSION: The absence of
      specific IgM antibodies against mumps virus is relatively often seen in
      vaccinated indivi-duals; nevertheless, the test is routinely used in patients
      with suspected active infection. The test for IgA antibodies, which is not
      routinely performed, significantly increased the detection rate of the disease.
      Based on the results of the present study, it can be concluded that the
      combination of the anti-mumps IgM and IgA assays increased the effectiveness of
      the serological diagnosis at the onset of clinical symptoms from less than 52% to
      nearly 72%.

PMID- 25872992
TI  - [A case of tuberculous meningitis associated with persistently reduced CD4+ T
      lymphocyte counts].
AB  - A case history is presented of a 35-year-old man admitted to the hospital with
      tuberculous meningitis complicated by caseous necrosis of cervical lymph nodes
      and thrombosis of the left jugular vein. Another complication, malignant brain
      edema, appeared more than one year after discharge from hospital and was managed
      at the neurosurgery department. The most probable cause was a post-inflammatory
      obstruction of the cerebrospinal fluid pathways. A challenging finding, observed
      repeatedly while in hospital and at follow ups after discharge, was medium
      significant CD4+ T cell lymphopenia, with the lowest CD4+ T cell count of 308
      cells/MUl of peripheral blood. For this reason, the patient was screened several
      times for anti-HIV antibodies, but always with a negative result. Active
      tuberculous infection was considered as another possible reason behind persistent
      CD4+ T cell lymphopenia. However, imaging and laboratory analyses were not
      suggestive of tuberculosis. The patient is currently in good condition and his
      CD4+ T lymphocyte counts returned to normal at seven years of follow-up. It is
      underlined that patients after tuberculous meningitis need a long-term follow-up.

PMID- 25872993
TI  - [Impact of climate changes on the incidence of tick-borne encephalitis in the
      Czech Republic in 1982-2011].
AB  - STUDY OBJECTIVE: To analyse the impact of climate changes on the increase in
      human cases of tick-borne encephalitis (TBE) in three high-incidence regions of
      the Czech Republic over the period 1982 to 2011. MATERIAL AND METHODS: Data on
      TBE cases were derived from the national reporting system EPIDAT. TBE is a
      reportable infectious disease in the Czech Republic. This study analysed data on
      TBE cases from three high-incidence regions that vary relatively widely in the
      average altitude and biotope types. The meteorological data for the study period,
      obtained from 26 stations of the Czech Hydrometeorological Institute (CHMI) which
      make standard meteorological measurements, were checked for correctness. The
      average altitude was determined for each study region. The STATISTICA 6 software
      was used for the basic statistical analysis (lit.). Pearsons correlation
      coefficient was used to assess the strength of the relationship between the
      variables and the 5% level was set as the criterion of statistical significance.
      The impact of the time lag between the epidemiological and meteorological
      quantities was also tested. RESULTS: The impact of the meteorological quantities
      temperature and precipitation rate on the occurrence of 6,229 TBE cases in three
      administrative regions varying in biotopes, altitude, and epidemiological
      characteristics of TBE infection was assessed. When evaluating the 30-year period
      1982-2011 year by year in three regions, a significant correlation was found
      between TBE onset and average air temperature in 100%, 90%, and 80% of years,
      with 11-20-day intervals to the onset of the disease. A significant correlation
      between the incidence of TBE cases and the precipitation rate was observed for
      40%, 43%, and 40% of years. When considering the summary results for the overall
      study period divided into three seasons (March-April, May-June, July-November), a
      significant correlation was identified between TBE incidence and temperature in
      all three seasons, with 0-30-day intervals to the onset, in all three regions.
      When considering the relationships between TBE incidence, air temperature, and
      precipitation rate for the overall study period divided into three seasons (March
      April, May-June, July-November), a significant correlation was identified between
      TBE incidence and temperature in all three regions. A correlation between TBE
      incidence and precipitation rate was only found for the period May-November.
      Moreover, the impact of air temperature and precipitation rate in the second half
      of the previous year on TBE incidence in the first half of the following year was
      tested. A positive correlation between air temperature and TBE incidence in the
      first half of the following year was found in three regions for 79.3%, 62.1%, and
      48.3% of years of the study period. A positive correlation between precipitation
      rate and TBE incidence was only found in these regions for 3.4%, 17.2%, and 6.9%
      of years of the study period. CONCLUSIONS: From the study results, it follows
      that air temperature had a major impact on TBE incidence in the regions studied.
      A correlation between TBE incidence and precipitation rate was found clearly less
      often, mostly in summer and autumn months. Air temperature and precipitation rate
      in the second half of the previous year did not have a major impact on TBE
      incidence in the first half of the following year.

PMID- 25872994
TI  - [A multifactor epidemiological analysis of risk factors for pancreatic cancer in
      women].
AB  - STUDY OBJECTIVE: A multifactor analysis of risk factors for pancreas cancer in
      women. MATERIAL AND METHODS: A case-control study was conducted in three centres
      in the Czech Republic (Olomouc, Ostrava, and Ceske Budejovice) in 2006-2009. In
      total, 226 women (129 pancreas cancer cases, 97 controls) were included in the
      study. Statistical analysis was performed, the crude odds ratio (OR) was
      calculated, and logistic regression analysis was used at a 5% level of
      statistical significance. RESULTS: A statistically significant inverse
      association was found between pancreatic cancer and oral contraceptives (OR 0.21;
      95% CI: 0.07-0.69). Pregnancy and number of pregnancies or gynecological surgical
      procedures did not show any association with pancreatic cancer. No significant
      difference in the first menstrual period was found between pancreatic cancer
      patients and controls. CONCLUSIONS: The study results showed inverse association
      between pancreatic cancer and oral contraceptives (OR 0.21; 95% CI: 0.07-0.69),
      controlled alcohol consumption (OR 0.26; 95% CI: 0.12-0.55), and anti-inflamatory
      drug use (OR 0.10; 95% CI: 0.02-0.41).

PMID- 25872995
TI  - [The populations attitudes to colorectal cancer screening in the Czech Republic].
AB  - BACKGROUND: The mortality of colorectal cancer (CRC) is significant worldwide.
      There is good evidence for benefits of the CRC screening in mortality reduction.
      Since 2009, the population of the Czech Republic have had two CRC screening
      options from which to choose: a faecal occult blood test (FOBT) at the age of 50
      to be repeated every two years or primary screening colonoscopy (PSC) at the age
      of 55. General practitioners play a crucial role in the CRC screening programme.
      The CRC screening adherence of the Czech population is poor and does not exceed
      25%. MATERIAL AND METHODS: The aims of the study were to analyse the reasons
      behind the low CRC screening adherence of the Czech population, to classify the
      populations attitudes, and to identify the barriers. A questionnaire survey was
      conducted in a Czech energy company with 13,000 employees in 2011-2012. The
      questionnaire was administered electronically by e-mail or directly at the
      workplace. RESULTS: The questionnaire response rate was 31.3% (4070). The pool of
      respondents consisted of 2804 (68.9%) females and 1266 (31.1%) males. Of the
      respondents, 1345 (33.1%) were aged over 50 years (73.5% women and 26.5% men). Of
      the cohort aged over 50, 68.65% of women and 63.2% of men took a FOBT. Ten
      percent of respondents aged over 50 years have never heard of CRC screening and
      32.8% of this age category have never participated in CRC screening. The main
      reasons for not taking a FOBT were feeling well and having no health problems
      (38.8%) or FOBT not offered the by the general practitioner (27.8%). Other
      reasons were no time to do so, fear of the result, unsure of the procedure,
      unawareness of what FOBT is, or uncomfortable about the test procedure. On the
      other hand, 8.37% of the participants aged between 15 and 39 years and 20.7% of
      those aged between 40 and 49 years have already taken a FOBT. Overall, 15.4% of
      respondents prefer the new alternative, PSC, as the CRC screening option.
      Significant differences in CRC screening adherence are seen between
      administrative regions of the Czech Republic and between education levels.
      CONCLUSIONS: From the results, it follows that a considerable proportion of the
      population of the Czech Republic do not understand the principle of CRC screening
      and its methods. Enough room has been left to promote education on CRC screening
      for both the public and general practitioners. On the other hand, a large part of
      proactive individuals participate in CRC screening before the age of 50.

PMID- 25872996
TI  - [Prevalence of selected congenital anomalies in the Czech Republic: congenital
      anomalies of the central nervous system and gastrointestinal tract].
AB  - OBJECTIVE: Analysis of the prevalence of selected congenital anomalies in the
      Czech Republic in 1994-2009. DESIGN: Retrospective epidemiological analysis of
      the postnatal and overall (including prenatally diagnosed cases) prevalence of
      congenital anomalies from the database of the National Registry of Congenital
      Anomalies of the Czech Republic. MATERIAL AND METHODS: Data from the National
      Registry of Congenital Anomalies (NRCA) maintained by the Institute of Health
      Information and Statistics of the Czech Republic (IHIS CR) were used. The
      analysis was carried out for the entire Czech Republic, based on the data from
      1994 to 2009. Additional data on prenatally diagnosed anomalies were obtained
      from medical genetics centres and laboratories in the Czech Republic. This study
      analyzed the postnatal and overall (including prenatally diagnosed cases)
      prevalence of congenital anomalies. More detailed analysis was carried out for
      the following diagnoses: anencephaly, spina bifida, encephalocoele, congenital
      hydrocephalus, omphalocoele, gastroschisis, oesophageal atresia and stenosis,
      anorectal anomalies, and diaphragmatic hernia. Prevalence trends were analysed
      using Poisson regression. RESULTS: In 2009, a total of 118 348 live births were
      recorded in the Czech Republic, 60 368 boys and 57 980 girls. Of this total, 4
      653, i.e. 2 745 boys and 1 908 girls, were diagnosed with congenital anomalies.
      In 2007-2009, the total of life births with congenital anomalies ranged between
      4.6 and 4.8 thousand per year. The respective ranges in this three-year period
      were in the order of 2.7 and 2.8 thousand per year for boys and 1.9 thousand per
      year for girls. The prevalence of postnatally diagnosed anencephaly was minimal,
      as most cases were diagnosed prenatally, and the data did not vary significantly.
      The prevalence of postnatally diagnosed cases remained at the same level. The
      effectiveness of the prenatal diagnosis of spina bifida increased and thus the
      prevalence of postnatally diagnosed cases decreased. The prevalence of prenatally
      diagnosed encephalocoele increased and that of postnatally diagnosed cases varied
      between years, with no clear trend. The prevalence of omphalocoele varied for
      both prenatally and postnatally diagnosed cases; nevertheless, the effectiveness
      of prenatal diagnosis of this defect increases. The prevalence of gastroschisis
      remained unchanged, but the number of live births with this diagnosis showed a
      non-significant upward trend. If the trend reflects the real situation, it could
      be a result of a changed approach to prenatal diagnosis due to advances in
      corrective surgery of this defect. The prevalence of live births with congenital
      hydrocephalus showed a downward trend in the second half of the period 1994-2009
      thanks to the improved diagnosis. The prevalence rates of live births with
      congenital esophageal and anorectal anomalies were slightly increasing. The
      prevalence of congenital diaphragmatic hernia varied between years but the
      overall prevalence appeared to be slightly increasing. CONCLUSION: The prevalence
      of some congenital anomalies (spina bifida, omphalocoele, and congenital
      hydrocephalus) showed a downward trend over the study period 1994-2009, mainly as
      a result of effective prenatal diagnosis. The prevalence of other congenital
      anomalies such as anencephaly or encephalocoele remained unchanged in live
      births. As for anencephaly, postnatally diagnosed cases were rare as the prenatal
      diagnosis was close to 100 %. The trend in encephalocoele is explained by the low
      incidence of this diagnosis in the population. The third group of postnatally
      diagnosed congenital anomalies such as gastroschisis or esophageal and anorectal
      anomalies were on the rise. As for gastroschisis, the reason was the changed
      approach to prenatal diagnosis due to good prognosis of this operable defect. The
      prevalence of congenital esophageal and anorectal anomalies varied between years,
      with a slowly increasing trend, similarly to diaphragmatic hernia.

PMID- 25873000
TI  - A novel splicing mutation of TMPRSS6 in a Chinese child with iron-refractory iron
      deficiency anaemia.

PMID- 25873003
TI  - Autism and inborn errors of metabolism: how much is enough?

PMID- 25873004
TI  - Abdominal aorta as an alternative access route for transcatheter aortic valve
      replacement.
AB  - A variety of access routes have been employed for transcatheter aortic valve
      replacement (TAVR). We report a TAVR case using the abdominal aorta as the direct
      access route when other approaches are not feasible.

PMID- 25873005
TI  - Self-Assembly of an Amphiphilic pi-Conjugated Dyad into Fibers: Ultrafast and
      Ultrasensitive Humidity Sensor.
AB  - The self-assembly of an amphiphilic monomolecular electron acceptor-donor dyad
      into electroactive pi-pi stacked fibrillar structures can be triggered by
      irradiation with visible light. These fibers, exposing hydrophilic ethylene
      glycol in their external shell, show unique characteristics as resistive humidity
      sensors that exhibit high sensitivity and ultrafast response. 

PMID- 25873006
TI  - Immediate Nephroureterectomy or After Attempting Conservative Treatment, on
      Elective Indications, for Upper Urinary Tract Urothelial Carcinoma: Comparison of
      the Pathology Reports on a Retrospective Monocentric Study.
AB  - OBJECTIVE: Conservative treatment (CT) with flexible ureteroscopy and laser
      ablation is an alternative to radical nephroureterectomy (RNU) for the treatment
      of the upper urinary tract urothelial carcinoma (UTUC). The purpose of this study
      was to compare the pathology results obtained after immediate RNU or after
      attempt of CT for elective indication. PATIENTS AND METHODS: A retrospective
      study was conducted in a single tertiary center. All patients who had an RNU for
      urothelial carcinoma between 2007 and 2012 have been included. The patients were
      classified into two groups: group 1 is immediate RNU, and group 2 is RNU after CT
      (only elective indications). Preoperative data collected were as follows: age,
      sex, chronic kidney failure, radiological classification for cancer staging
      (TNM), tumor size, localization, and multifocal indication of CT. The
      pathological RNU data collected were tumor stage and grade. The T stage was
      divided into two groups (primary endpoint): pTa-T1-T2 and pT3-T4. The chi(2) test
      and Mann-Whitney was performed to compare the independent qualitative and
      quantitative variables, respectively. RESULTS: A total of 51 patients were
      included (40 patients in the immediate RNU group and 11 patients in the delayed
      RNU group after CT). Patients in both groups had comparable characteristics
      regarding age, sex, location, T stage, and preoperative tumor grade. On final
      pathology, 23 tumors were classified as pTa-T1-T2 in the immediate RNU group
      compared with 6 in the delayed RNU group. Seventeen and five tumors were
      classified as T3 in group 1 and group 2, respectively. These results were not
      significantly different between both groups (p=0.866). The pathological RNU grade
      was not significantly different between the groups. CONCLUSION: Within the limits
      of this retrospective study, the pathological RNU data showed no significant
      difference when RNU was done immediately or after CT for UTUC.

PMID- 25873007
TI  - One-step Conversion of Furfural into 2-Methyltetrahydrofuran under Mild
      Conditions.
AB  - One-step direct conversion of biomass-derived furfural to 2-methyltetrahydrofuran
      was realized under atmospheric pressure over a dual solid catalyst based on two
      stage-packed Cu-Pd in a reactor; this is the first report that one-step
      conversion of furfural resulted in high yield of 2-methyltetrahydrofuran (97.1 %)
      under atmospheric pressure. This strategy provided a successive hydrogenation
      process, which avoids high H2 pressure, uses the reactor efficiently, and
      eliminates the product-separation step. Therefore, it could enhance the overall
      efficiency as a result of low cost and high yield. 

PMID- 25873008
TI  - Effect of fermented medicinal plants on growth performance, nutrient
      digestibility, fecal noxious gas emissions, and diarrhea score in weanling pigs.
AB  - BACKGROUND: Antibiotics used as growth promoters in livestock have been banned in
      the European Union since 2006. Alternatives of antibiotics have focused on
      phytogenic plants, such as herbs and medicinal plants. No studies have evaluated
      the use of fermented medicinal plants (FMP) made up of Gynura procumbens,
      Rehmannia glutinosa and Scutellaria baicalensis in weanling pigs. Therefore, an
      experiment was conducted to determine the effects of FMP on growth performance,
      nutrient digestibility, fecal noxious gas emissions and diarrhea score in
      weanling pigs. RESULTS: FMP supplementation increased (P < 0.05) average daily
      gain, average daily feed intake, gain:feed, apparent total tract digestibility of
      dry matter, nitrogen and gross energy compared with NC treatment, while a linear
      effect (P < 0.05) was observed on those criteria. Ammonia, total mercaptans and
      hydrogen sulfide concentrations were decreased (P < 0.05) by the supplementation
      of FMP compared with NC. Additionally, diarrhea score was lower (P < 0.05) by FMP
      addition compared with NC during days 0-7 and days 8-14. CONCLUSION: These
      results suggested that FMP could be used as an alternative to antibiotics by
      enhancing growth performance and nutrient digestibility, and decreasing fecal
      noxious gas emission and early diarrhea score of weanling pigs.

PMID- 25873009
TI  - Characterizing the Intermediates Compound I and II in the Cytochrome P450
      Catalytic Cycle with Nonlinear X-ray Spectroscopy: A Simulation Study.
AB  - Cytochrome P450 enzymes are an important family of biocatalysts that oxidize
      chemically inert C?H bonds. There are many unresolved questions regarding the
      catalytic reaction intermediates, in particular P450 Compound I (Cpd-I) and II
      (Cpd-II). By using simple molecular models, we simulate various X-ray
      spectroscopy signals, including X-ray absorption near-edge structure (XANES),
      resonant inelastic X-ray scattering (RIXS), and stimulated X-ray Raman
      spectroscopy (SXRS) of the low- and high-spin states of Cpd-I and II.
      Characteristic peak patterns are presented and connected to the corresponding
      electronic structures. These X-ray spectroscopy techniques are complementary to
      more conventional infrared and optical spectroscopy and they help to elucidate
      the evolving electronic structures of transient species along the reaction path. 

PMID- 25873011
TI  - Association of mutations in FLNA with craniosynostosis.
AB  - Mutations of FLNA, an X-linked gene that encodes the cytoskeletal protein filamin
      A, cause diverse and distinct phenotypes including periventricular nodular
      heterotopia and otopalatodigital spectrum disorders (OPDS). Craniofacial
      abnormalities associated with OPDS include supraorbital hyperostosis, down
      slanting palpebral fissures and micrognathia; craniosynostosis was previously
      described in association with FLNA mutations in two individual case reports. Here
      we present four further OPDS subjects who have pathological FLNA variants and
      craniosynostosis, supporting a causal link. Together with the previously reported
      patients, frontometaphyseal dysplasia was the most common clinical diagnosis
      (four of six cases overall); five patients had multiple suture synostosis with
      the sagittal suture being the most frequently involved (also five patients). No
      genotype-phenotype correlation was evident in the distribution of FLNA mutations.
      This report highlights the need to consider a filaminopathy in the differential
      diagnosis of craniosynostosis, especially in the presence of atypical cranial or
      skeletal features. 

PMID- 25873010
TI  - Clinical relevance of 8q23, 15q13 and 18q21 SNP genotyping to evaluate colorectal
      cancer risk.
AB  - To determine if the at-risk single-nucleotide polymorphism (SNP) alleles for
      colorectal cancer (CRC) could contribute to clinical situations suggestive of an
      increased genetic risk for CRC, we performed a prospective national case-control
      study based on highly selected patients (CRC in two first-degree relatives, one
      before 61 years of age; or CRC diagnosed before 51 years of age; or multiple
      primary CRCs, the first before 61 years of age; exclusion of Lynch syndrome and
      polyposes) and controls without personal or familial history of CRC. SNPs were
      genotyped using SNaPshot, and statistical analyses were performed using Pearson's
      chi(2) test, Cochran-Armitage test of trend and logistic regression. We included
      1029 patients and 350 controls. We confirmed the association of CRC risk with
      four SNPs, with odds ratio (OR) higher than previously reported: rs16892766 on
      8q23.3 (OR: 1.88, 95% confidence interval (CI): 1.30-2.72; P=0.0007); rs4779584
      on 15q13.3 (OR: 1.42, CI: 1.11-1.83; P=0.0061) and rs4939827 and rs58920878/Novel
      1 on 18q21.1 (OR: 1.49, CI: 1.13-1.98; P=0.007 and OR: 1.49, CI: 1.14-1.95;
      P=0.0035). We found a significant (P<0.0001) cumulative effect of the at-risk
      alleles or genotypes with OR at 1.62 (CI: 1.10-2.37), 2.09 (CI: 1.43-3.07), 2.87
      (CI: 1.76-4.70) and 3.88 (CI: 1.72-8.76) for 1, 2, 3 and at least 4 at-risk
      alleles, respectively, and OR at 1.71 (CI: 1.18-2.46), 2.29 (CI: 1.55-3.38) and
      6.21 (CI: 2.67-14.42) for 1, 2 and 3 at-risk genotypes, respectively. Combination
      of SNPs may therefore explain a fraction of clinical situations suggestive of an
      increased risk for CRC. 

PMID- 25873012
TI  - Pathogenic mitochondrial mt-tRNA(Ala) variants are uniquely associated with
      isolated myopathy.
AB  - Pathogenic mitochondrial DNA (mtDNA) point mutations are associated with a wide
      range of clinical phenotypes, often involving multiple organ systems. We report
      two patients with isolated myopathy owing to novel mt-tRNA(Ala) variants. Muscle
      biopsy revealed extensive histopathological findings including cytochrome c
      oxidase (COX)-deficient fibres. Pyrosequencing confirmed mtDNA heteroplasmy for
      both mutations (m.5631G>A and m.5610G>A) whilst single-muscle fibre segregation
      studies (revealing statistically significant higher mutation loads in COX
      deficient fibres than in COX-positive fibres), hierarchical mutation segregation
      within patient tissues and decreased steady-state mt-tRNA(Ala) levels all provide
      compelling evidence of pathogenicity. Interestingly, both patients showed very
      high-mutation levels in all tissues, inferring that the threshold for impairment
      of oxidative phosphorylation, as evidenced by COX deficiency, appears to be
      extremely high for these mt-tRNA(Ala) variants. Previously described mt-tRNA(Ala)
      mutations are also associated with a pure myopathic phenotype and demonstrate
      very high mtDNA heteroplasmy thresholds, inferring at least some
      genotype:phenotype correlation for mutations within this particular mt-tRNA gene.

PMID- 25873013
TI  - Collapsed haplotype pattern method for linkage analysis of next-generation
      sequence data.
AB  - Recent advances in next-generation sequencing (NGS) make it possible to directly
      sequence genomes and exomes of individuals with Mendelian diseases and screen
      sequence data for causal variants. With the reduction in cost of NGS, DNA samples
      from entire families can be sequenced and linkage analysis can be performed
      directly using NGS data. Inspired by 'burden' tests, which are used for complex
      trait rare variant association studies, we developed the collapsed haplotype
      pattern (CHP) method for linkage analysis. Using data from several deafness genes
      we demonstrate that the CHP method is substantially more powerful than analyzing
      individual variants. Unlike applying NGS data filtering approaches, the CHP
      method provides statistical evidence of a gene's involvement in disease etiology
      and is also less likely to exclude causal variants in the presence of phenocopies
      and/or reduced penetrance. The CHP method was implemented in the SEQLinkage
      software package, which can perform linkage analysis on NGS data or can generate
      data compatible with many linkage analysis programs, reviving them for use in NGS
      era. 

PMID- 25873014
TI  - Clinical Utility Gene Card for: autosomal recessive cone-rod dystrophy.

PMID- 25873016
TI  - Topiramate: a review of analytical approaches for biological matrices.
AB  - Topiramate is an anticonvulsant drug and it has been used worldwide for a wide
      range of applications. It is mainly indicated for the treatment of partial and
      generalized seizures, including Lennox Gastant Syndrome and generalized tonic
      clonic seizures, and prophylactic treatment of migraine. Different analytical
      approaches by high-performance liquid chromatography have been described to
      analyze topiramate because of its lack of chromophore groups, including
      derivatization with UV-absorbing moieties, derivatization with fluorescent
      moieties, refractive index detection, conductivity detection, chemiluminescent
      nitrogen detection, evaporative light scattering detection and MS detection. In
      addition, some methods for determination of topiramate by capillary
      electrophoresis have been published as well as by gas chromatography. Thus, it is
      beneficial to evaluate and compare these papers before selecting the most
      suitable method/detector to analyze this drug. This systematic review provides a
      description of the main analytical methods available for the analysis of
      topiramate in biological matrices. Each of these methods is briefly discussed
      considering the detector used with HPLC. HPLC coupled with MS is the main
      technique used for topiramate analysis in biological matrices, mainly in the
      electrospray ionization-negative mode.

PMID- 25873015
TI  - Regulating biobanking with children's tissue: a legal analysis and the experts'
      view.
AB  - Many current paediatric studies concern relationships between genes and
      environment and discuss aetiology, treatment and prevention of Mendelian and
      multifactorial diseases. Many of these studies depend on collection and long-term
      storage of data and biological material from affected children in biobanks.
      Stored material is a source of personal information of the donor and his family
      and could be used in an undesirable context, potentially leading to
      discrimination and interfering with a child's right to an open future. Here, we
      address the normative framework regarding biobanking with residual tissue of
      children, protecting the privacy interests of young biobank donors (0-12 years).
      We analyse relevant legal documents concerning storage and use of children's
      material for research purposes. We explore the views of 17 Dutch experts involved
      in paediatric biobank research and focus on informed consent for donation of
      leftover tissue as well as disclosure of individual research findings resulting
      from biobank research. The results of this analysis show that experts have no
      clear consensus about the appropriate rules for storage of and research with
      children's material in biobanks. Development of a framework that provides a fair
      balance between fundamental paediatric research and privacy protection is
      necessary. 

PMID- 25873017
TI  - Integrity of white matter microstructure in alcoholics with and without
      Korsakoff's syndrome.
AB  - Alcohol dependence results in two different clinical forms: "uncomplicated"
      alcoholism (UA) and Korsakoff's syndrome (KS). Certain brain networks are
      especially affected in UA and KS: the frontocerebellar circuit (FCC) and the
      Papez circuit (PC). Our aims were (1) to describe the profile of white matter
      (WM) microstructure in FCC and PC in the two clinical forms, (2) to identify
      those UA patients at risk of developing KS using their WM microstructural
      integrity as a biomarker. Tract-based spatial statistics and nonparametric voxel
      based permutation tests were used to compare diffusion tensor imaging (DTI) data
      in 7 KS, 20 UA, and 14 healthy controls. The two patient groups were also pooled
      together and compared to controls. k-means classifications were then performed on
      mean fractional anisotropy values of significant clusters across all subjects for
      two fiber tracts from the FCC (the middle cerebellar peduncle and superior
      cerebellar peduncle) and two tracts from the PC (fornix and cingulum). We found
      graded effects of WM microstructural abnormalities in the PC of UA and KS. UA
      patients classified at risk of developing KS using fiber tracts of the PC from
      DTI data also had the lowest scores of episodic memory. That finding suggests
      that WM microstructure could be used as a biomarker for early detection of UA
      patients at risk of developing KS.

PMID- 25873018
TI  - Joint skewness and its application in unsupervised band selection for small
      target detection.
AB  - Few band selection methods are specially designed for small target detection. It
      is well known that the information of small targets is most likely contained in
      non-Gaussian bands, where small targets are more easily separated from the
      background. On the other hand, correlation of band set also plays an important
      role in the small target detection. When the selected bands are highly
      correlated, it will be unbeneficial for the subsequent detection. However, the
      existing non-Gaussianity-based band selection methods have not taken the
      correlation of bands into account, which generally result in high correlation of
      obtained bands. In this paper, combining the third-order (third-order tensor) and
      second-order (correlation) statistics of bands, we define a new concept, named
      joint skewness, for multivariate data. Moreover, we also propose an easy-to
      implement approach to estimate this index based on high-order singular value
      decomposition (HOSVD). Based on the definition of joint skewness, we present an
      unsupervised band selection for small target detection for hyperspectral data,
      named joint skewness band selection (JSBS). The evaluation results demonstrate
      that the bands selected by JSBS are very effective in terms of small target
      detection. 

PMID- 25873019
TI  - Quality by design coupled with near infrared in formulation of transdermal
      glimepiride liposomal films.
AB  - This study is aimed at developing glimepiride (GMD) liposomal films using quality
      by design (QbD) and process analytical technology (PAT) principles. Risk analysis
      and Plackett-Burman design were utilized to evaluate formulation variables in two
      paths. Internal path included liposomal parameters (phosphatidylserine,
      cholesterol and drug concentrations, and pH of hydration medium). External path
      constituted films parameters, namely, polymer, plasticizer, and permeation
      enhancer percentages. As a PAT tool, near infrared (NIR)-based chemometric
      analysis was used in quantifying GMD contents. Liposomal formulations showed
      maximum GMD entrapment capacity of 41.9% with vesicular size of 0.51 MUm at
      phospholipid to cholesterol to drug weight ratio of 2:1:0.8. Its transdermal
      films showed elongation ratio of 75%, folding endurance of 700-fold, 16.6% and
      26.8% drug release after 1 and 12 h, respectively. Moreover, 3D response spaces
      for GMD entrapment and release characteristics were established. Regarding NIR
      analysis, partial-least-square regression model was accurate in quantifying drug
      content as indicated by the low root-mean-squared error of calibrations and
      prediction of 0.031 and 0.032, and bias values of 0.0015 and 0.0021,
      respectively. In conclusion, this study highlights the level of understanding
      that can be accomplished through a well-designed research based on QbD and PAT
      paradigms.

PMID- 25873020
TI  - Effect of secondary hyperparathyroidism serum on endothelial cells and
      intervention with Klotho.
AB  - The aim of the present study was to investigate the effect of the serum of
      patients with secondary hyperparathyroidism (SHPT) on endothelial cells and to
      examine the protective effect and the possible mechanism of Klotho. A total of
      three types of mixed serum from 15 patients with SHPT scheduled for
      parathyroidectomy, 10 chronic kidney disease (CKD) patients at stage 5 without
      SHPT and 15 healthy volunteers were collected. Initially, human umbilical vein
      endothelial cells (HUVECs) were incubated in vitro with the three types of serum
      and levels of proliferation were compared by assessing viable cell numbers with
      cell counting kit-8 (CCK-8). Subsequently, HUVECs were divided into three groups:
      Control group (healthy serum medium), SHPT group (SHPT serum) and Klotho
      treatment group (SHPT serum and Klotho). The proliferative and apoptotic levels
      of endothelial cells were evaluated by CCK-8 and flow cytometry, respectively.
      The levels of extracellular signal-regulated kinase (ERK1/2) and phosphorylated
      forms of ERK1/2 (p-ERK1/2) were detected using western blotting (with or without
      ERK1/2 inhibitor PD98059). The synthesis of nitric oxide (NO) was measured using
      the nitrate reduction method. The proliferation of HUVECs was inhibited by the
      serum from SHPT patients and CKD-5 patients without SHPT and the inhibitory
      effects of the SHPT serum were the most marked (P<0.05). Inhibition of HUVEC
      proliferation by SHPT serum occurred in a concentration-dependent manner within a
      specific range (5-20%; P<0.05) and also in a time-dependent manner within 6-24 h.
      Proliferation was partly restored and apoptosis was inhibited when 50-100 ng/ml
      Klotho was added into 10% SHPT serum (P<0.05). At the same time, the expression
      of p-ERK1/2 was upregulated, which may be inhibited by PD98059. The synthesis of
      NO was decreased in the SHPT group (P<0.05) and increased following treatment
      with Klotho (P<0.05). The results of the present study indicated that the
      proliferation of HUVECs was inhibited by the serum from SHPT patients. Klotho may
      partly antagonize this effect due to its inhibition of HUVEC apoptosis and
      upregulation of p-ERK1/2.

PMID- 25873021
TI  - Problems With Using Patient Retention in the Evaluation of Mental Health
      Providers: Differences in Type of Dropout.
AB  - OBJECTIVE: Retention, or its opposite, dropout, is a common metric of
      psychotherapy quality, but using it to assess provider performance can be
      problematic. Differences among providers in numbers of general dropouts, "good"
      dropouts (patients report positive treatment experiences and outcome), and "bad"
      dropouts (patients report negative treatment experiences and outcome) were
      evaluated. METHODS: Patient records were paired with satisfaction surveys
      (N=3,054). Binomial mixed-effects models were used to examine differences among
      providers by dropout type. RESULTS: Thirty-four percent of treatment episodes
      resulted in dropout. Of these, 14% were bad dropouts and 27% were good dropouts.
      Providers accounted for approximately 17% of the variance in general dropout and
      10% of the variance in both bad dropout and good dropout. The ranking of
      providers fluctuated by type of dropout. CONCLUSIONS: Provider assessments based
      on patient retention should offer a way to isolate dropout type, given that
      nonspecific metrics may lead to biased estimates of performance.

PMID- 25873022
TI  - Depression Treatment Uptake in Integrated Primary Care: How a "Warm Handoff" and
      Other Factors Affect Decision Making by Latinos.
AB  - OBJECTIVE: Integrated behavioral health care has the potential to reduce barriers
      to mental health treatment among low-income and minority populations. This study
      aimed to identify predictors of Latino patients' decision to follow through with
      referrals to depression treatment in an integrated primary care setting,
      including type of referral (a "warm handoff" from a primary care provider [PCP]
      to a behavioral health care provider or a prescribed referral). METHODS: The
      authors conducted a sequential medical record review of 431 patients referred for
      depression treatment in integrated behavioral health services followed by
      qualitative semistructured interviews with a subsample of 16 patients. RESULTS:
      English-speaking Latinos were four times less likely to attend an initial visit
      within two months of a referral if they received a warm handoff rather than a
      prescribed referral. The strength of the patient-provider relationship and the
      quality of the referral experience, including whether the PCP addressed patients'
      health literacy and expectations for depression care, affected patients' decision
      to engage in depression treatment. CONCLUSIONS: Engaging Latinos in needed mental
      health treatment is a challenge, even when treatment is provided in primary care
      settings. Warm handoffs are considered effective components of engagement, but
      this study suggests that the effectiveness of warm handoffs may vary depending on
      the patient's primary language. The following factors seem important to engaging
      Latinos into care: patient-provider relationship, quality of the referral
      process, addressing expectations about depression care, and reducing
      communication barriers, including health literacy and linguistic barriers. Future
      studies of engagement strategies should explore these factors.

PMID- 25873023
TI  - Pathways to Care for First Psychiatric Admissions in Lisbon.
AB  - OBJECTIVES: This report characterizes pathways to first psychiatric admission and
      describes their relationship to patients' sociodemographic and clinical features.
      METHODS: Eighty-four patients consecutively admitted for the first time in 2009
      2010 to a Lisbon district psychiatric department were interviewed. Associations
      between pathways and clinical and sociodemographic variables were explored
      through univariate and multivariate analysis. RESULTS: Most patients (N=49, 58%)
      went directly to the psychiatric emergency department and were admitted, without
      contacting any other care providers. This pathway was significantly associated
      with male gender, involuntary admission, referral by a family member, fewer
      people per room in the household, and lower probability of previous contact with
      mental health services. CONCLUSIONS: The most striking feature was the high
      prevalence of direct access to the psychiatric emergency department with
      subsequent admission. Use of this direct pathway suggests that these patients
      were bypassing care filters, with negative consequences. Specific
      sociodemographic variables, but not diagnosis, were associated with filter
      bypass.

PMID- 25873024
TI  - Service Use and Self-Reported Symptoms Among Persons With Positive PTSD Screens
      and Serious Mental Illness.
AB  - OBJECTIVE: Although many studies have reported higher rates of trauma exposure
      and posttraumatic stress disorder (PTSD) among persons with severe mental
      illness, the screening, diagnosis, and treatment of PTSD in public mental health
      centers remain at a suboptimal level and PTSD is often overlooked and untreated.
      This study used routine PTSD screening and service use data in electronic medical
      records to determine the association of PTSD, psychiatric symptoms, and service
      use in a sample of individuals with serious mental illness in a community-based
      treatment setting. METHODS: The sample included 1,834 active clients between
      January 2007 and November 2010 who were screened for PTSD and who completed the
      24-item Behavior and Symptom Identification Scale (BASIS-24). Service data
      included services provided a year before and a year after the screening date.
      RESULTS: PTSD was associated with more severe psychiatric symptoms and increased
      no-show rates but not with increased service use or use of high-intensity
      services. PTSD likelihood interacted with race in accounting for elevated scores
      among African Americans on the psychosis domain of the BASIS-24. CONCLUSIONS:
      PTSD screening is feasible and recommended in service environments and may
      contribute significantly to better understanding of racial-ethnic and other
      differences in service use and diagnostic practices.

PMID- 25873025
TI  - Quality of Life and Functioning One Year After Experiencing Accumulated Coercive
      Events During Psychiatric Admission.
AB  - OBJECTIVES: The study aimed to determine the number of accumulated coercive
      events experienced by patients during inpatient admission, the patients'
      functioning and quality of life (QOL) one year after discharge, and associations
      between these variables and patient characteristics and between follow-up
      outcomes and number of accumulated coercive events. METHODS: A prospective cohort
      study was undertaken at three community services and an independent hospital in
      Ireland (N=162). Accumulated coercive events scores were based on patients' legal
      status, perceived coercion, and exposure to physical restraint, seclusion, or
      forced medication. RESULTS: Most (68%) experienced at least one coercive event.
      Lower functioning predicted more coercive events. At follow-up, the mean
      subjective QOL score was 63% of the highest possible score, objective QOL
      improved for 15% of participants, and functioning improved for 70%. Accumulated
      coercive events did not predict these outcomes. CONCLUSIONS: Coercive events
      during psychiatric admission appeared unrelated to functioning and QOL at follow
      up.

PMID- 25873026
TI  - Emergency Psychiatry Experience, Resident Burnout, and Future Plans to Treat
      Publicly Funded Patients.
AB  - OBJECTIVE: This study examined psychiatry resident burnout in emergency
      departments and its association with residents' posttraining plans to care for
      Medicaid patients and others publicly insured. METHODS: Between November and
      December 2013, psychiatry residents in North Carolina were recruited for a cross
      sectional, Internet-based survey concerning emergency department experiences,
      attitudes about their roles, feelings of burnout, and posttraining intentions to
      treat Medicaid patients. The completion rate was 51% (N=91). RESULTS: In
      bivariate analyses (N=82 with an emergency psychiatry rotation), burnout was
      positively associated with frequent exhaustion (p<.001) and perceived suboptimal
      supervision by the attending physician (p<.01). Compared with other residents,
      residents planning to accept Medicaid after training had significantly lower
      burnout scores (p<.05). Experiencing assault in the emergency department
      indicated decreased likelihood of treating publicly insured patients after
      training (Medicaid, odds ratio=.09, p<.05). CONCLUSIONS: Adverse experiences with
      patient care in the emergency department during psychiatry residency appear to be
      linked to professional burnout and threaten to shape long-term plans regarding
      care for publicly insured patients.

PMID- 25873027
TI  - Housing Programs for Homeless Individuals With Mental Illness: Effects on Housing
      and Mental Health Outcomes.
AB  - OBJECTIVE: This systematic review analyzed the best available research in the
      United States on permanent supportive housing programs for homeless individuals
      with mental illness and the effect of these programs on housing status and mental
      health. It updates older and broader reviews that included weaker studies or
      those that did not analyze permanent housing as an input and housing and mental
      health as primary outcomes. METHODS: The literature search (1980-2013) yielded 14
      studies (randomized controlled trials and quasi-experimental studies). RESULTS:
      The studies found that a majority of participants placed in experimental housing
      programs with case management support remained in housing for at least one year
      or experienced more days housed than homeless relative to a comparison group.
      Although this finding is in line with previous literature reviews on permanent
      supportive housing, this analysis found limitations in each of the 14 reviewed
      studies, such as attrition, selection and response bias, imprecise definitions
      and implementation of housing programs, and a lack of appropriate controls. Only
      three of the reviewed studies reported using a housing fidelity assessment tool
      to test whether the housing intervention was faithful to theoretical standards,
      and conceptions and implementation of housing varied widely across studies,
      threatening internal and external validity. CONCLUSIONS: Pitfalls in the best
      available studies on permanent supportive housing programs in the United States
      limit the ability of research to inform the policy goal of ending chronic
      homelessness and demonstrate a need for further experimental research upon which
      to make funding and policy decisions, especially in light of prioritized federal
      funds.

PMID- 25873028
TI  - Measuring Performance in Psychiatry: A Call to Action.
AB  - Many recent public and private strategies aimed at improving the quality and
      efficiency of the U.S. health care system focus on measuring, reporting on, and
      providing incentives for improving quality. In behavioral health care, despite
      recent efforts, quality measurement for even the more common conditions is less
      well developed than for comparable general medical conditions. The absence of a
      comprehensive set of well-accepted measures capable of demonstrating the value of
      behavioral health treatment makes building a case for devoting resources to
      treatment more difficult. This Open Forum reviews the current state of behavioral
      health quality measurement, describes the criteria relevant to assessing
      measures, and provides a case for encouraging the development, collection, and
      routine use of functional outcome measures in behavioral health care. 

PMID- 25873030
TI  - Mental Health Service Use Among Lesbian, Gay, and Bisexual Older Adults.
AB  - OBJECTIVE: Empirical efforts to measure use of mental health services among
      lesbian, gay, and bisexual (LGB) older adults have been notably lacking. Thus
      this study assessed associations between sexual orientation and mental health
      service use among older adults and determined the mediating role of nonspecific
      psychological distress, excessive alcohol use, and self-perceived poor general
      medical health. METHODS: Data from the 2011 New York City Community Health Survey
      were analyzed. The analytic sample comprised 5,138 adults ages 50 and over.
      Logistic regression modeling was used to examine associations between sexual
      orientation (LGB versus heterosexual) and past-year mental health service use
      (counseling or medication), adjusting for sociodemographic and clinical
      characteristics. Mediation analyses using bootstrapping were conducted. RESULTS:
      Among LGB older adults, 23.9% reported receiving counseling, and 23.4% reported
      taking psychiatric medication in the past year. LGB respondents were
      significantly more likely than heterosexuals to have received counseling
      (adjusted odds ratio [AOR]=2.16, 95% confidence interval [CI]=1.49-3.13) and
      psychiatric medication (AOR=1.97, CI=1.36-2.86). Psychological distress,
      excessive alcohol use, and self-perceived poor general medical health did not
      mediate the association between sexual orientation and mental health service use.
      CONCLUSIONS: LGB older adults were more likely than heterosexuals to utilize
      mental health services, and this association was not explained by indicators of
      general medical, mental, or behavioral health.

PMID- 25873029
TI  - Client Views of Engagement in the RAISE Connection Program for Early Psychosis
      Recovery.
AB  - OBJECTIVE: This study assessed factors that facilitated or impeded clients'
      engagement in services offered by the Recovery After an Initial Schizophrenia
      Episode (RAISE) Connection Program for youths and young adults experiencing early
      psychosis. It was part of the larger RAISE Implementation and Engagement Study.
      METHODS: Thematic qualitative analyses of data from in-person, semistructured
      interviews with 32 clients were used to examine experiences of program services,
      staff practices, clients' engagement behaviors, and related factors, such as
      expectations, family involvement, illness, and setting. Eighteen clients were
      well engaged with services, and 14 were not. Thirteen were interviewed early in
      their program involvement (two to nine months after enrollment) and 18 others
      later (12 to 24 months after enrollment). RESULTS: Four domains of factors
      influenced engagement: individualized care, program attributes, family member
      engagement, and personal attributes. A central factor was the program's focus on
      clients' life goals. For many interviewees, engagement hinged substantially on
      receiving what could be considered nonclinical services, such as supported
      education and employment. Other key factors were individualized services and
      staff interactions that were respectful, warm, and flexible; engagement of family
      members; and a focus on shared decision making. CONCLUSIONS: The findings help
      explain the Connection Program's effectiveness regarding client engagement and
      deepen understanding of treatment engagement for youths and young adults
      experiencing early psychosis. The individualized, flexible, recovery-focused, and
      assertive model of services and client-staff interaction, incorporating shared
      decision making and a focus on client life goals, should be implemented and
      sustained in services for this population.

PMID- 25873031
TI  - Improving As(III) adsorption on graphene based surfaces: impact of chemical
      doping.
AB  - On the basis of quantum chemistry calculations, the adsorption of As(III) onto
      graphene based adsorbents has been studied. The energetic and molecular
      properties that characterize the adsorption have been analyzed, and new
      adsorbents were proposed. The experimentally reported inefficient adsorption of
      As(III) by intrinsic graphene is theoretically characterized by a low adsorption
      energy (~0.3 eV), which is decreased by solvent effects. Two stable conformations
      were found for the adsorbent-adsorbate systems. The As(III) removal by unmodified
      oxidized graphene (GO) reaches a medium size adsorption strength (<~0.8 eV),
      while still remaining low for high removal efficiency from a water environment.
      While As(III) adsorption onto boron, nitrogen and phosphorous doped graphene is
      not favored with respect to the pristine adsorbent, aluminium, silicon and iron
      embedded graphene can adsorb As(III) by both chemical and physical interactions
      with high adsorption energies (>~1 eV), even stable considering a solvent
      environment. The efficiency of the adsorbents for As(III) removal is sorted as Al
      G > Fe-G ? Si-G ? GO ? G. Therefore, Al, Si and Fe doped graphene are considered
      as potential materials for efficient As(III) removal.

PMID- 25873032
TI  - Targeting matriptase in breast cancer abrogates tumour progression via impairment
      of stromal-epithelial growth factor signalling.
AB  - Matriptase is an epithelia-specific membrane-anchored serine protease that has
      received considerable attention in recent years because of its consistent
      dysregulation in human epithelial tumours, including breast cancer. Mice with
      reduced levels of matriptase display a significant delay in oncogene-induced
      mammary tumour formation and blunted tumour growth. The abated tumour growth is
      associated with a decrease in cancer cell proliferation. Here we demonstrate by
      genetic deletion and silencing that the proliferation impairment in matriptase
      deficient breast cancer cells is caused by their inability to initiate activation
      of the c-Met signalling pathway in response to fibroblast-secreted pro-HGF.
      Similarly, inhibition of matriptase catalytic activity using a selective small
      molecule inhibitor abrogates the activation of c-Met, Gab1 and AKT, in response
      to pro-HGF, which functionally leads to attenuated proliferation in breast
      carcinoma cells. We conclude that matriptase is critically involved in breast
      cancer progression and represents a potential therapeutic target in breast
      cancer. 

PMID- 25873034
TI  - Changes in the osmolarity of the embryonic microenvironment induce neural tube
      defects.
AB  - Many maternal disorders that modify the embryonic microenvironment, such as a
      change in osmolarity, can affect development, but how these changes influence the
      early embryo remains obscure. Neural tube defects, for example, are common
      congenital disorders found in fetus and neonates. In this study, we investigated
      the impact of anisotonic osmolarity (unequal osmotic pressures) on neural tube
      development in the early chick embryo, finding that neuronal cell differentiation
      was impaired in the neural tube due to enhanced apoptosis and repressed cell
      proliferation. Anisotonic osmolarity also affected normal development of the
      neural crest, which in turn influenced abnormal development of the neural tube.
      As neural tube development is highly dependent on the proper expression of bone
      morphogenetic protein 4 (BMP4), paired box 7 (PAX7), and sonic hedgehog (SHH)
      genes in the dorsal and ventral regions along the tube, we investigated the
      impact of anisotonic osmolarity on their expression. Indeed, small changes in
      osmolarity could positively and negatively impact the expression of these
      regulatory genes, which profoundly affected neural tube development. Thus, both
      the central and peripheral nervous systems were perturbed by anisotonic
      consitions as a consequence of the abnormal expression of key genes within the
      developing neural tube.

PMID- 25873033
TI  - Plant defense phenotypes determine the consequences of volatile emission for
      individuals and neighbors.
AB  - Plants are at the trophic base of terrestrial ecosystems, and the diversity of
      plant species in an ecosystem is a principle determinant of community structure.
      This may arise from diverse functional traits among species. In fact, genetic
      diversity within species can have similarly large effects. However, studies of
      intraspecific genetic diversity have used genotypes varying in several complex
      traits, obscuring the specific phenotypic variation responsible for community
      level effects. Using lines of the wild tobacco Nicotiana attenuata genetically
      altered in specific well-characterized defense traits and planted into
      experimental populations in their native habitat, we investigated community-level
      effects of trait diversity in populations of otherwise isogenic plants. We
      conclude that the frequency of defense traits in a population can determine the
      outcomes of these traits for individuals. Furthermore, our results suggest that
      some ecosystem-level services afforded by genetically diverse plant populations
      could be recaptured in intensive monocultures engineered to be functionally
      diverse. 

PMID- 25873035
TI  - The association of patient complexities with antibiotic ordering.
AB  - BACKGROUND: Antibiotic treatment decisions for medically complex patients are
      complicated, as the risk of undertreatment may be severe, whereas overtreatment
      may be associated with adverse effects and the emergence of antibiotic resistant
      pathogens. OBJECTIVE: To determine the influence of patient complexities on
      providers' decisions to prescribe antibiotics in 3 common hospital-based clinical
      vignettes. DESIGN: A physician survey. SETTING: Three urban medical centers in
      Los Angeles County, California. PARTICIPANTS: Hospital-based physicians.
      MEASUREMENTS: Physicians were presented 3 clinical vignettes, with variations by
      patient age, comorbidity burden, functional status, and follow-up, and asked to
      choose the best antibiotic regimen. We described the association of additional
      patient complexity on the proportion of guideline-adherent antibiotic choices.
      RESULTS: In the survey, 28% to 49% of physicians recommended antibiotics that
      were inconsistent with national guidelines. This percentage increased to 48% to
      63% for medically complex patients, defined as those with either older age, high
      medical comorbidity burden, poor functional status, or limited follow-up after
      hospital discharge (P < 0.01). CONCLUSIONS: In 3 vignettes depicting common
      clinical scenarios among hospitalized adults, inappropriate antibiotic use was
      prevalent and occurred more often for patients with medical complexities.
      Treatment guidelines should consider addressing medically complex patients in the
      context of infection management.

PMID- 25873036
TI  - Regioselective syntheses of 1,2-benzothiazines by rhodium-catalyzed annulation
      reactions.
AB  - Rhodium-catalyzed directed carbene insertions into aromatic C?H bonds of S-aryl
      sulfoximines lead to intermediates, which upon dehydration provide 1,2
      benzothiazines in excellent yields. The domino-type process is regioselective and
      shows a high functional-group tolerance. It is scalable, and the only by-products
      are dinitrogen and water. Three illustrative transformations underscore the
      synthetic value of the products. 

PMID- 25873042
TI  - The dopamine theory of addiction: 40 years of highs and lows.
AB  - For several decades, addiction has come to be viewed as a disorder of the
      dopamine neurotransmitter system; however, this view has not led to new
      treatments. In this Opinion article, we review the origins of the dopamine theory
      of addiction and discuss the ability of addictive drugs to elicit the release of
      dopamine in the human striatum. There is robust evidence that stimulants increase
      striatal dopamine levels and some evidence that alcohol may have such an effect,
      but little evidence, if any, that cannabis and opiates increase dopamine levels.
      Moreover, there is good evidence that striatal dopamine receptor availability and
      dopamine release are diminished in individuals with stimulant or alcohol
      dependence but not in individuals with opiate, nicotine or cannabis dependence.
      These observations have implications for understanding reward and treatment
      responses in various addictions. 

PMID- 25873043
TI  - Double layer lift-off nanofabrication controlled gaps of nanoelectrodes with sub
      100 nm by nanoimprint lithography.
AB  - Basic research on nanoelectronics is often limited by the high cost and large
      scale methods to fabricate electrodes with controlled gap size in nanometer
      scales. Here nanoelectrodes with a controlled gap size of sub-100 nm were
      fabricated by modified nanoimprint lithography (NIL) via a double-layer lift-off
      process utilizing polymethylmethacrylate (PMMA) and polydimethylglutarimide
      (PMGI) as the lift-off resist. Firstly the patterns of the electrode mold were
      transferred onto the upper PMMA layer by NIL techniques and then through
      controlling the developing time and concentration of developer of the PMGI under
      layer, regulating the exact gap size of the transferred metal nanoelectrode. The
      result indicated that the 'undercut' phenomenon was observed of the PMGI transfer
      layer during the developing process; through controlling the feature size of the
      undercut length, the gap size of the transferred metal nanoelectrode was
      precisely controlled, which showed shrinkage behavior. The nanoelectrodes with
      gap sizes of 800, 400, 200, and 100 nm can be reduced to about 440, 120, 80, and
      70 nm. Our result provides a low-cost and large-scale route to prepare
      nanoelectrodes with controlled gap size, which can be valuable for current
      efforts in nanoelectronics. 

PMID- 25873038
TI  - Decision making in the ageing brain: changes in affective and motivational
      circuits.
AB  - As the global population ages, older decision makers will be required to take
      greater responsibility for their own physical, psychological and financial well
      being. With this in mind, researchers have begun to examine the effects of ageing
      on decision making and associated neural circuits. A new 'affect-integration
      motivation' (AIM) framework may help to clarify how affective and motivational
      circuits support decision making. Recent research has shed light on whether and
      how ageing influences these circuits, providing an interdisciplinary account of
      how ageing can alter decision making. 

PMID- 25873044
TI  - Comparative effectiveness of home blood pressure telemonitoring (HBPTM) plus
      nurse case management versus HBPTM alone among Black and Hispanic stroke
      survivors: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Black and Hispanic stroke survivors experience higher rates of
      recurrent stroke than whites. This disparity is partly explained by
      disproportionately higher rates of uncontrolled hypertension in these
      populations. Home blood pressure telemonitoring (HBPTM) and nurse case management
      (NCM) have proven efficacy in addressing the multilevel barriers to blood
      pressure (BP) control and reducing BP. However, the effectiveness of these
      interventions has not been evaluated in stroke patients. This study is designed
      to evaluate the comparative effectiveness, cost-effectiveness and sustainability
      of these two telehealth interventions in reducing BP and recurrent stroke among
      high-risk Black and Hispanic stroke survivors with uncontrolled hypertension.
      METHODS/DESIGN: A total of 450 Black and Hispanic patients with recent
      nondisabling stroke and uncontrolled hypertension are randomly assigned to one of
      two 12-month interventions: 1) HBPTM with wireless feedback to primary care
      providers or 2) HBPTM plus individualized, culturally-tailored, telephone-based
      NCM. Patients are recruited from stroke centers and primary care practices within
      the Health and Hospital Corporations (HHC) Network in New York City. Study visits
      occur at baseline, 6, 12 and 24 months. The primary outcomes are within-patient
      change in systolic BP at 12 months, and the rate of stroke recurrence at 24
      months. The secondary outcome is the comparative cost-effectiveness of the
      interventions at 12 and 24 months; and exploratory outcomes include changes in
      stroke risk factors, health behaviors and treatment intensification. Recruitment
      for the stroke telemonitoring hypertension trial is currently ongoing.
      DISCUSSION: The combination of two established and effective interventions along
      with the utilization of health information technology supports the sustainability
      of the HBPTM + NCM intervention and feasibility of its widespread implementation.
      Results of this trial will provide strong empirical evidence to inform clinical
      guidelines for management of stroke in minority stroke survivors with
      uncontrolled hypertension. If effective among Black and Hispanic stroke
      survivors, these interventions have the potential to substantially mitigate
      racial and ethnic disparities in stroke recurrence. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT02011685 . Registered 10 December 2013.

PMID- 25873045
TI  - Fuzheng Kang'ai decoction combined with gefitinib in advanced non-small cell lung
      cancer patients with epidermal growth factor receptor mutations: study protocol
      for a randomized controlled trial.
AB  - BACKGROUND: Patients with advanced non-small cell lung cancer (NSCLC) harboring
      mutations of the epidermal growth factor receptor (EGFR) gene respond well to the
      EGFR tyrosine kinase inhibitor (TKI) gefitinib. Chinese herbal medicine (CHM) has
      been used as a complementary therapy for cancer for decades in China. CHM was
      proved to be effective in improving the quality of life (QOL) and reducing the
      toxicity associated with chemotherapy in patients with NSCLC. The purpose of the
      present trial is to determine whether CHM (Fuzheng Kang'ai decoction (FZKA), a
      CHM formula) combined with gefitinib results in longer progression-free survival
      with less toxicity than gefitinib alone. METHODS/DESIGN: This is a randomized,
      placebo-controlled, double-blind trial. This trial is designed to determine if
      CHM (FZKA) combined with gefitinib results in longer progression-free survival
      with less toxicity than gefitinib alone. A total of 70 NSCLC patients with EGFR
      mutations will be randomly assigned to treatment group (gefitinib plus FZKA
      granules) or control group (gefitinib plus placebo). The primary endpoint is
      progression-free survival. Secondary endpoints are: (1) overall survival; (2)
      disease control rate; (3) QOL, measured with the questionnaire of Functional
      Assessment of Cancer Therapy-lung (FACT-L 4.0) and Lung Cancer Symptom Scale and
      (4) safety. DISCUSSION: In previous clinical practice, we found that CHM (FZKA)
      could improve the therapeutic efficacy of gefitinib. This study will provide
      objective evidence to evaluate the efficiency of CHM combined with gefitinib in
      NSCLC patients with EGFR mutations, and may provide a novel regimen for patients
      with NSCLC. TRIAL REGISTRATION: Chinese Clinical Trial Registry ( www.chictr.org
      ): ChiCTR-IOR-14005679 , registered 17 December 2014.

PMID- 25873047
TI  - From "special measures" to "good" in less than a year.

PMID- 25873046
TI  - Efficacy and safety of Ban-Lan-Gen granules in the treatment of seasonal
      influenza: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Ban-Lan-Gen (BLG) is a traditional Chinese herbal medicine. It has
      been used for the prevention and treatment of virus-related respiratory diseases
      such as influenza virus infection. BLG contains some antiviral compounds, but few
      evidence-based clinical studies have been conducted to assess its efficacy
      against influenza. We assessed the effects of BLG (including efficacy and safety)
      on the treatment of seasonal influenza in an evidence-based clinical trial.
      METHODS/DESIGN: We conducted a randomized, double-blinded, oseltamivir- and
      placebo-controlled, parallel-design clinical trial. A total of 177 subjects are
      going to be recruited after satisfying the criteria: (i) 18 to 65 years of age;
      (ii) illness onset within 36 h; (3) axillary temperature >=38.0 degrees C; and
      (iv) positive influenza (type A/B) virus test. Subjects will be assigned randomly
      into three groups in equal proportions: oseltamivir treatment, BLG granule
      treatment, and placebo treatment. Each group receives 5-day treatment and is
      followed up 1, 3, 5, 7 and 21 days later. Symptoms and patient compliance are
      recorded, and virus/serum viral antibodies tested. We will use the primary
      outcome, secondary outcome, and safety indicators to evaluate the efficacy and
      safety of BLG granules in the treatment of seasonal influenza. DISCUSSION: We
      have described the first clinical trial for treatment using a single herb against
      influenza A and B viruses in China. We will hold a large-scale clinical trial to
      comprehensively evaluate the effectiveness and safety of BLG against influenza
      infection based on the results of this pilot study. And this clinical trial will
      serve as an example for the study of other traditional herbal medicines in
      evidence-based clinical trials. TRIAL REGISTRATION: This study has been
      registered at ClinicalTrials.gov: NCT02232945 (3 September 2014).

PMID- 25873048
TI  - Immunolocalization of thymidylate synthase as a favorable prognostic marker in
      estrogen receptor-positive breast carcinoma.
AB  - BACKGROUND: Thymidylate synthase (TS) is an enzyme involved in DNA synthesis, and
      it is a target for 5-fluorouracil. Previous studies have demonstrated that TS is
      a potent estrogen-induced gene in breast carcinoma cells, suggesting the
      importance of TS in estrogen-receptor (ER)-positive breast carcinoma. TS
      immunolocalization has been reported previously, but the clinicopathological
      significance of TS in ER-positive breast carcinoma still remains unclear.
      PATIENTS AND METHODS: We immunolocalized TS in 178 breast carcinoma tissues in
      total, and examined its significance according to the ER-status. RESULTS: TS
      status was positive in 58% of ER-positive ductal carcinoma in situ (DCIS) cases,
      and it was significantly associated with the Ki-67 and progesterone receptor
      (PR). Moreover, in ER-positive DCIS patients who received aromatase inhibitor
      (AI) before surgery, TS immunoreactivity was significantly decreased after AI
      treatment. In ER-positive invasive ductal carcinoma (IDC) cases, TS status was
      significantly associated with PR, and it turned out an independent favorable
      prognostic factor for recurrence of the patients by multivariate analysis. On the
      other hand, TS status was positively correlated with pathological T factor in ER
      negative IDC cases, and tended to have a worse prognosis for disease-free
      survival of the patients. CONCLUSION: These results suggest that TS expression is
      mainly regulated by estrogen in ER-positive breast carcinoma and is associated
      with estrogen-mediated proliferation. TS status is a favorable prognostic factor
      in ER-positive IDC patients, which is different from the ER-negative cases.

PMID- 25873049
TI  - The emerging landscape of circular RNA ciRS-7 in cancer (Review).
AB  - Circular RNAs (circRNAs) are a novel class of non-coding RNA molecules
      ubiquitously present in the cytoplasm of eukaryotic cells. CircRNAs are generated
      from exons or introns via multiple mechanisms. A recently identified circRNA,
      ciRS-7, can regulate the activities of miRNAs, mRNAs, and RBP to exert specific
      biological effects. Also, ciRS-7 acts as a natural competing endogenous RNA,
      a.k.a. 'super sponge' of microRNA-7 (miR-7) that sequesters and competitively
      inhibits the activity of miR-7. This competition between ciRS-7 and miR-7 may
      have profound effects on oncogenesis. This review will summarize the origin and
      functions of ciRS-7 and discuss the relationship among ciRS-7, its target
      molecules and cancer.

PMID- 25873051
TI  - Testing for changes in troponin over first hour speeds up detection of acute
      myocardial infarction.

PMID- 25873050
TI  - Optimizing early child development for young children with non-anemic iron
      deficiency in the primary care practice setting (OptEC): study protocol for a
      randomized controlled trial.
AB  - BACKGROUND: Three decades of research suggests that prevention of iron deficiency
      anemia (IDA) in the primary care setting may be an unrealized and unique
      opportunity to prevent poor developmental outcomes in children. A longitudinal
      study of infants with IDA showed that the developmental disadvantage persists
      long term despite iron therapy. Early stages of iron deficiency, termed non
      anemic iron deficiency (NAID), provide an opportunity for early detection and
      treatment before progression to IDA. There is little research regarding NAID,
      which may be associated with delayed development in young children. The aim of
      this study is to compare the effectiveness of four months of oral iron treatment
      plus dietary advice, with placebo plus dietary advice, in improving developmental
      outcomes in children with NAID and to conduct an internal pilot study.
      METHODS/DESIGN: From a screening cohort, those identified with NAID (hemoglobin
      >=110 g/L and serum ferritin <14 MUg/L) are invited to participate in a
      pragmatic, multi-site, placebo controlled, blinded, parallel group, superiority
      randomized trial. Participating physicians are part of a primary healthcare
      research network called TARGet Kids! Children between 12 and 40 months of age and
      identified with NAID are randomized to receive four months of oral iron treatment
      at 6 mg/kg/day plus dietary advice, or placebo plus dietary advice (75 per
      group). The primary outcome, child developmental score, is assessed using the
      Mullen Scales of Early Learning at baseline and at four months after
      randomization. Secondary outcomes include an age appropriate behavior measure
      (Children's Behavior Questionnaire) and two laboratory measures (hemoglobin and
      serum ferritin levels). Change in developmental and laboratory measures from
      baseline to the end of the four-month follow-up period will be analyzed using
      linear regression (analysis of covariance method). DISCUSSION: This trial will
      provide evidence regarding the association between child development and NAID,
      and the effectiveness of oral iron to improve developmental outcomes in children
      with NAID. The sample size of the trial will be recalculated using estimates
      taken from an internal pilot study. TRIAL REGISTRATION: This trial was registered
      with Clinicaltrials.gov (identifier: NCT01481766 ) on 22 November 2011.

PMID- 25873052
TI  - A living document: reincarnating the research article.
AB  - The limitations of the traditional research paper are well known and widely
      discussed; however, rather than seeking solutions to the problems created by this
      model of publication, it is time to do away with a print era anachronism and
      design a new model of publication, with modern technology embedded at its heart.
      Instead of the current system with multiple publications, across multiple
      journals, publication could move towards a single, evolving document that begins
      with trial registration and then extends to include the full protocol and results
      as they become available, underpinned by the raw clinical data and all code used
      to obtain the result. This model would lead to research being evaluated
      prospectively, based on its hypothesis and methodology as stated in the study
      protocol, and move away from considering serendipitous results to be synonymous
      with quality, while also presenting readers with the opportunity to reliably
      evaluate bias or selective reporting in the published literature. 

PMID- 25873053
TI  - Protective effects of Semen Crotonis Pulveratum on trinitrobenzene sulphonic acid
      induced colitis in rats and H2O2-induced intestinal cell apoptosis in vitro.
AB  - Ulcerative colitis (UC) is a chronic inflammatory bowel disease. Semen Crotonis
      Pulveratum (SCP) has been used as a traditional medicine for the treatment of UC.
      However, its molecular mechanisms of action have not yet been elucidated. In the
      present study, we aimed to investigate the preliminary mechanisms of the role of
      SCP on trinitrobenzene sulphonic acid (TNBS)-induced UC in rats and hydrogen
      peroxide (H2O2)-induced intestinal cell apoptosis in vitro. Wistar rats (n=9 per
      group) were randomly divided into 4 groups: the normal control group, the UC
      group, the UC + SCP group and the UC + sulfasalazine group as a positive control.
      The proportion of CD4+CD25+ T cells and CD4+CD25+Foxp3+ Tregs, and the expression
      levels of interleukin (IL)-6 and IL-10 in the peripheral blood, as well as the
      expression levels of cyclooxygenase-2 (COX-2) and intercellular adhesion molecule
      1 (ICAM-1) in the colon tissues were determined by flow cytometry, ELISA and
      immunohistochemical staining, respectively. Rat intestinal epithelial (IEC-6)
      cell apoptosis induced by H2O2 was determined by TUNEL assay, flow cytometry
      using Annexin V/propidium iodide (PI) staining and western blot analysis of
      caspase-3 activation, respectively. Significantly higher proportions of
      circulating CD4+CD25+ T cells and CD4+CD25+Foxp3+ Tregs were present in the UC +
      SCP group compared with the UC group. A significantly decreased expression of IL
      6 and an increased expression of IL-10 were also observed in the UC + SCP group
      compared with UC group. SCP significantly reduced the UC-induced increase in the
      expression of COX-2 and ICAM-1 in the colon tissues. SCP inhibited cell apoptosis
      and caspase-3 activation induced by H2O2 in the ICE-6 cells. Our data thus
      indicate that SCP inhibits inflammation in UC by increasing the proportion of
      circulating Tregs, altering cytokine production and decreasing COX-2 and ICAM-1
      expression. In addition it protects against H2O2-induced intestinal cell
      apoptosis in vitro.

PMID- 25873054
TI  - Erratum to: disappointment and adherence among parents of newborns allocated to
      the control group: a qualitative study of a randomized clinical trial.

PMID- 25873057
TI  - Improving adherence with oral antiemetic agents in patients with breast cancer
      receiving chemotherapy.
AB  - PURPOSE: In this small breast cancer-dedicated solo practice, a retrospective
      medical record review disclosed the following: significant rate of chemotherapy
      related nausea and vomiting and discordance between patient-reported compliance
      with prescribed antiemetics and medical record documentation of compliance. As
      part of the curriculum for the American Society of Clinical Oncology (ASCO)
      Quality Training Program, a quality improvement project was developed to improve
      adherence to oral antiemetics in our patients with breast cancer receiving highly
      emetogenic chemotherapy. PATIENTS AND METHODS: The following steps were
      undertaken in plan-do-study-act cycles to improve adherence: enhanced patient
      education at time of chemotherapy consent, implementation of standardized in
      person or e-mail contact with our patients receiving chemotherapy, and
      improvement of our electronic health record documentation of adherence to oral
      antiemetics. A run chart was generated to analyze our data. RESULTS: After our
      interventions, the percentage of patients who took their antiemetics as
      prescribed rose from a baseline of 49% to 79%. CONCLUSION: Significant
      improvement in adherence to oral antiemetics among patients with breast cancer
      receiving chemotherapy was achieved and sustained in this small-practice setting
      using the framework provided by participation in the ASCO Quality Training
      Program.

PMID- 25873056
TI  - Reviewing cancer care team effectiveness.
AB  - PURPOSE: The management of cancer varies across its type, stage, and natural
      history. This necessitates involvement of a variety of individuals and groups
      across a number of provider types. Evidence from other fields suggests that a
      team-based approach helps organize and optimize tasks that involve individuals
      and groups, but team effectiveness has not been fully evaluated in oncology
      related care. METHODS: We undertook a systematic review of literature published
      between 2009 and 2014 to identify studies of all teams with clear membership, a
      comparator group, and patient-level metrics of cancer care. When those teams
      included two or more people with specialty training relevant to the care of
      patients with cancer, we called them multidisciplinary care teams (MDTs). After
      reviews and exclusions, 16 studies were thoroughly evaluated: two addressing
      screening and diagnosis, 11 addressing treatment, two addressing palliative care,
      and one addressing end-of-life care. The studies included a variety of end points
      (eg, adherence to quality indicators, patient satisfaction with care, mortality).
      RESULTS: Teams for screening and its follow-up improved screening use and reduced
      time to follow-up colonoscopy after an abnormal screen. Discussion of cases
      within MDTs improved the planning of therapy, adherence to recommended
      preoperative assessment, pain control, and adherence to medications. We did not
      see convincing evidence that MDTs affect patient survival or cost of care, or
      studies of how or which MDT processes and structures were associated with
      success. CONCLUSION: Further research should focus on the association between
      team processes and structures, efficiency in delivery of care, and mortality.

PMID- 25873055
TI  - Short-term vagal nerve stimulation improves left ventricular function following
      chronic heart failure in rats.
AB  - Increasing numbers of animal and clinical investigations have demonstrated the
      effectiveness of long-term electrical vagal nerve stimulation (VNS) on chronic
      heart failure (CHF). The present study investigated the effects of short-term VNS
      on the hemodynamics of cardiac remodeling and cardiac excitation-contraction
      coupling (ECP) in an animal model of CHF following a large myocardial infarction.
      At 3 weeks subsequent to ligation of the left coronary artery, the surviving rats
      were randomized into vagal and sham-stimulated groups. The right vagal nerve of
      the CHF rats was stimulated for 72 h. The vagal nerve was stimulated with
      rectangular pulses of 40 ms duration at 1 Hz, 5 V. The treated rats, compared
      with the untreated rats, had significantly higher left ventricular ejection
      fraction (54.86 +/- 9.73, vs. 45.60 +/- 5.51%; P=0.025) and left ventricular
      fractional shortening (25.31 +/- 6.30, vs. 15.42 +/- 8.49%; P=0.013), and lower
      levels of brain natriuretic peptide (10.07 +/- 2.63, vs. 19.95 +/- 5.22 ng/ml;
      P=0.001). The improvement in cardiac pumping function was accompanied by a
      decrease in left ventricular end diastolic volume (1.11 +/- 0.50, vs. 1.54 +/-
      0.57 cm(3); P=0.032) and left ventricular end systolic volume (0.50 +/- 0.28, vs.
      0.87 +/- 0.36 cm(3); P=0.007). Furthermore, the expression levels of ryanodine
      receptor type 2 (RyR2) and sarcoplasmic reticulum calcium adenosine
      triphosphatase (SERCA2) were significantly higher in the treated rats compared
      with the untreated rats (P=0.011 and P=0.001 for RyR2 and SERCA2, respectively).
      Therefore, VNS was beneficial to the CHF rats through the prevention of cardiac
      remodeling and improvement of cardiac ECP.

PMID- 25873058
TI  - Big data infrastructure for cancer outcomes research: implications for the
      practicing oncologist.

PMID- 25873059
TI  - Teams and teamwork during a cancer diagnosis: interdependency within and between
      teams.
AB  - This article discusses the care process among three groups (primary care,
      radiology, and surgery) aiding a 57-year-old woman during her screening
      mammography and diagnosis of breast cancer. This is the first in a series of
      articles exploring principles and topics relevant to teams guiding clinicians
      involved in cancer care. The challenges demonstrated in this case illustrate how
      clinicians work within and between groups to deliver this first phase of cancer
      care. The case helps demonstrate the differences between groups and teams.
      Focusing on the patient and the overall process of care coordination can help
      move groups toward becoming teams who deliver better care by identifying and
      managing goals, roles, and interdependent care tasks. Care providers and
      researchers can use the case to consider their own work and essential aspects of
      teamwork needed to improve care, patient outcomes, and the evidence that supports
      each. 

PMID- 25873060
TI  - Cancer Treatment in Patients With HIV Infection and Non-AIDS-Defining Cancers: A
      Survey of US Oncologists.
AB  - PURPOSE: HIV-infected individuals with non-AIDS-defining cancers are less likely
      to receive cancer treatment compared with uninfected individuals. We sought to
      identify provider-level factors influencing the delivery of oncology care to HIV
      infected patients. METHODS: A survey was mailed to 500 randomly selected US
      medical and radiation oncologists. The primary outcome was delivery of standard
      treatment, assessed by responses to three specialty-specific management
      questions. We used the chi(2) test to evaluate associations between delivery of
      standard treatment, provider demographics, and perceptions of HIV-infected
      individuals. Multivariable logistic regression identified associations using
      factor analysis to combine several correlated survey questions. RESULTS: Our
      response rate was 60%; 69% of respondents felt that available cancer management
      guidelines were insufficient for the care of HIV-infected patients with cancer;
      45% never or rarely discussed their cancer management plan with an HIV
      specialist; 20% and 15% of providers were not comfortable discussing cancer
      treatment adverse effects and prognosis with their HIV-infected patients with
      cancer, respectively; 79% indicated that they would provide standard cancer
      treatment to HIV-infected patients. In multivariable analysis, physicians
      comfortable discussing adverse effects and prognosis were more likely to provide
      standard cancer treatment (adjusted odds ratio, 1.52; 95% CI, 1.12 to 2.07).
      Physicians with concerns about toxicity and efficacy of treatment were
      significantly less likely to provide standard cancer treatment (adjusted odds
      ratio, 0.67; 95% CI, 0.53 to 0.85). CONCLUSION: Provider-level factors are
      associated with delivery of nonstandard cancer treatment to HIV-infected
      patients. Policy change, provider education, and multidisciplinary collaboration
      are needed to improve access to cancer treatment.

PMID- 25873061
TI  - Venous thromboembolism prophylaxis and treatment in patients with cancer:
      American Society of Clinical Oncology clinical practice guideline update.

PMID- 25873062
TI  - Incorporating patient-reported outcomes to improve emotional distress screening
      and assessment in an ambulatory oncology clinic.
AB  - PURPOSE: Assessment of distress and well-being of patients with cancer is not
      always documented or addressed in a clinical visit, reflecting a need for
      improved psychosocial screening. METHODS: A multidisciplinary team completed
      process mapping for emotional distress assessment in two clinics. Barriers were
      identified through cause-and-effect analysis, and an intervention was chosen.
      Patient-reported outcomes were collected over 6 months using the validated
      National Comprehensive Cancer Network Emotional Distress Thermometer (EDT) paper
      tool. The American Society of Clinical Oncology Quality Oncology Practice
      Initiative (QOPI) measures were compared before and after intervention. RESULTS:
      During 6 months, a total of 864 tools were collected from 1,344 patients in two
      ambulatory clinics (64%). Electronic medical record documentation of distress
      increased from 19.2% to 34% during the 6 months before and after intervention.
      QOPI measures showed an increase in emotional well-being documentation. Of 29 new
      and 835 return patients, 62% indicated mild distress (EDT, 0 to 3), 18% moderate
      (EDT, 4 to 6), and 11% severe (EDT, 7 to 10). The average distress score of new
      patients was significantly higher than that of return patients (5.39 [n = 26] v
      2.52 [n = 754]; P < .001). The top problems for patients with moderate and severe
      distress were worry, fatigue, pain, and nervousness; depression and sadness were
      particularly noted in patients reporting severe distress. Eleven percent of
      patients were referred to the social worker on site. CONCLUSION: A pilot
      intervention collecting Patient-reported outcomes in two ambulatory clinics led
      to increase in psychosocial distress screening followed by sustained improvement,
      indicated by both process and QOPI measures.

PMID- 25873064
TI  - Evaluating the efficacy, safety and evolution of renal function with early
      initiation of everolimus-facilitated tacrolimus reduction in de novo liver
      transplant recipients: Study protocol for a randomized controlled trial.
AB  - BACKGROUND: Introduction of calcineurin inhibitors had led to improved survival
      rates in liver transplant recipients. However, long-term use of calcineurin
      inhibitors is associated with a higher risk of chronic renal failure,
      neurotoxicity, de novo malignancies, recurrence of hepatitis C viral (HCV)
      infection and hepatocellular carcinoma. Several studies have shown that
      everolimus has the potential to provide protection against viral replication,
      malignancy, and progression of fibrosis, as well as preventing nephrotoxicity by
      facilitating calcineurin inhibitor reduction without compromising efficacy. The
      Hephaistos study evaluates the beneficial effects of early initiation of
      everolimus in de novo liver transplant recipients. METHODS/DESIGN: Hephaistos is
      an ongoing 12-month, multi-center, open-label, controlled study aiming to enroll
      330 de novo liver transplant recipients from 15 centers across Germany. Patients
      are randomized in a 1:1 ratio (7-21 days post-transplantation) to receive
      everolimus (trough levels 3-8 ng/mL) with reduced tacrolimus (trough levels <5
      ng/mL), or standard tacrolimus (trough levels 6-10 ng/mL) after entering a run-in
      period (3-5 days post-transplantation). In the run-in period, patients are
      treated with induction therapy, mycophenolate mofetil, tacrolimus, and
      corticosteroids according to local practice. Randomization is stratified by HCV
      status and model of end-stage liver disease scores at transplantation. The
      primary objective of the study is to exhibit superior renal function (estimated
      glomerular filtration rate assessed by the Modification of Diet in Renal Disease
      (MDRD)-4 formula) with everolimus plus reduced tacrolimus compared to standard
      tacrolimus at Month 12. Other objectives are: to assess the incidence of treated
      biopsy-proven acute rejection, graft loss, or death; the incidences of components
      of the composite efficacy endpoint; renal function via estimated glomerular
      filtration rate using various formulae (MDRD-4, Nankivell, Cockcroft-Gault,
      chronic kidney disease epidemiology collaboration and Hoek formulae); the
      incidence of proteinuria; the incidence of adverse events and serious adverse
      events; the incidence and severity of cytomegalovirus and HCV infections and HCV
      related fibrosis. DISCUSSION: This study aims to demonstrate superior renal
      function, comparable efficacy, and safety in de novo liver transplant recipients
      receiving everolimus with reduced tacrolimus compared with standard tacrolimus.
      This study also evaluates the antiviral benefit by early initiation of
      everolimus. TRIAL REGISTRATION: NCT01551212 .

PMID- 25873065
TI  - Loss of alpha1,6-fucosyltransferase inhibits chemical-induced hepatocellular
      carcinoma and tumorigenesis by down-regulating several cell signaling pathways.
AB  - Up-regulation of core fucosylation catalyzed by alpha1,6-fucosyltransferase
      (Fut8) has been observed in hepatocellular carcinoma (HCC). Here, to explore the
      role of Fut8 expression in hepatocarcinogensis, we established the chemical
      induced HCC models in the male wild-type (WT; Fut8(+/+)), hetero (Fut8(+/-)), and
      knockout (KO; Fut8(-/-)) mice by use of diethylnitrosamine (DEN) and
      pentobarbital (PB). In the Fut8(+/+) and Fut8(+/-) mice, multiple large and
      vascularized nodules were induced with an increased expression of Fut8 after DEN
      and PB treatment. However, the formation of HCC in Fut8(-/-) mice was suppressed
      almost completely. This potent inhibitory effect of Fut8 deficiency on
      tumorigenesis was also confirmed by the abolished tumor formation of Fut8 KO
      human hepatoma cell line cells by use of a xenograft tumor model. Furthermore,
      loss of the Fut8 gene resulted in attenuated responses to epidermal growth factor
      (EGF) and hepatocyte growth factor (HGF) in the HepG2 cell line, which provides
      the possible mechanisms for the contribution of Fut8 to hepatocarcinogensis.
      Taken together, our study clearly demonstrated that core fucosylation acts as a
      critical functional modulator in the liver and implicated Fut8 as a prognostic
      marker, as well as a novel, therapeutic target for HCC.

PMID- 25873063
TI  - Collaboration Between Surgeons and Medical Oncologists and Outcomes for Patients
      With Stage III Colon Cancer.
AB  - PURPOSE: Collaboration between specialists is essential for achieving high-value
      care in patients with complex cancer needs. We explore how collaboration between
      oncologists and surgeons affects mortality and cost for patients requiring
      multispecialty cancer care. PATIENTS AND METHODS: This was a retrospective cohort
      study of patients with stage III colon cancer from SEER-Medicare diagnosed
      between 2000 and 2009. Patients were assigned to a primary treating surgeon and
      oncologist. Collaboration between surgeon and oncologist was measured as the
      number of patients shared between them; this has been shown to reflect advice
      seeking and referral relationships between physicians. Outcomes included hazards
      for all-cause mortality, subhazards for colon cancer-specific mortality, and cost
      of care at 12 months. RESULTS: A total of 9,329 patients received care from 3,623
      different surgeons and 2,319 medical oncologists, representing 6,827 unique
      surgeon-medical oncologist pairs. As the number of patients shared between
      specialists increased from to one to five (25th to 75th percentile), patients
      experienced an approximately 20% improved survival benefit from all-cause and
      colon cancer-specific mortalities. Specifically, for each additional patient
      shared between oncologist and surgeon, all-cause mortality improved by 5% (hazard
      ratio, 0.95; 95%CI, 0.92 to 0.97), and colon cancer-specific mortality improved
      by 5% (subhazard ratio, 0.95; 95% CI, 0.91 to 0.97). There was no association
      with cost. CONCLUSION: Specialist collaboration is associated with lower
      mortality without increased cost among patients with stage III colon cancer.
      Facilitating formal and informal collaboration between specialists may be an
      important strategy for improving the care of patients with complex cancers.

PMID- 25873066
TI  - Tissue proteomics of splenic marginal zone lymphoma.
AB  - Splenic marginal zone lymphoma (SMZL) is a rare chronic B lymphoproliferative
      disease, whose molecular pathogenesis has still not been well established. For
      the first time, a proteomic approach was undertaken to analyse the protein
      profiles of SMZL tissue. 1D and 2D Western blot, immunohistochemical analysis,
      and functional data mining were also performed in order to validate results,
      investigate protein species specific regulation, classify proteins, and explore
      their potential relationships. We demonstrated that SMZL is characterized by
      modulation of protein species related to energetic metabolism and apoptosis
      pathways. We also reported specific protein species (such as biliverdin reductase
      A, manganese superoxide dismutase, beta-2 microglobulin, growth factor receptor
      bound protein 2, acidic leucine-rich nuclear phosphoprotein 32 family member A,
      and Set nuclear oncogene) directly involved in NF-kB and BCR pathways, as well as
      in chromatin remodelling and cytoskeleton. Our findings shed new light on SMZL
      pathogenesis and provide a basis for the future development of novel biomarkers.
      The mass spectrometry proteomics data have been deposited to the ProteomeXchange
      Consortium with the dataset identifier PXD001124. 

PMID- 25873068
TI  - Lateral Bone Window Closing Technique with Poly-L-Lactic Acid (PLLA) Membrane in
      the Augmentation of the Maxillary Sinus without Grafting Material: Evaluation of
      Bone Healing in a Rabbit Model.
AB  - BACKGROUND: When augmenting the maxillary sinus without grafting material, the
      method used to cover the bony window is a subject of debate. PURPOSE: The purpose
      of this study was to evaluate the poly-L-lactic acid (PLLA) membrane as closing
      material of the lateral window in a maxillary sinus augmentation without bone
      grafting. MATERIALS AND METHODS: Augmentation of the maxillary sinus without
      grafting material and installation of titanium screws that fix the Schneiderian
      membrane were performed in 18 Japanese male white rabbits. The bony window was
      covered with a collagen membrane or PLLA membrane or no membrane. The animals
      were sacrificed at 4 or 8 weeks. New bone volume was calculated radiologically
      using microcomputed tomography (micro-CT). The samples were analyzed
      histologically after toluidine blue staining. RESULTS: No significant differences
      were observed in the new bone volume, as measured by micro-CT. However,
      histomorphometric analysis demonstrated the superiority of the PLLA membrane in
      new bone formation compared with the collagen membrane. CONCLUSION: The PLLA
      membrane is a suitable material to be applied for tissue regeneration in this
      animal model.

PMID- 25873067
TI  - The POSE study - panic control treatment versus panic-focused psychodynamic
      psychotherapy under randomized and self-selection conditions: study protocol for
      a randomized controlled trial.
AB  - BACKGROUND: Panic disorder with or without agoraphobia is a commonly occurring
      disorder affecting 2 to 3% of the population in Sweden. Untreated, panic disorder
      is a chronic condition that significantly increases the risk for psychiatric
      comorbidity, morbidity and mortality, employment difficulties, and healthcare
      utilization. Cognitive behavioral approaches are the recommended first-line
      treatment for panic disorder; however, many patients in routine care receive
      another evidence-based psychotherapy, including psychodynamic therapy. Allowing
      patients to choose among evidence-based approaches to panic disorder may improve
      outcomes and reduce overall health costs. Trials comparing the 'gold standard'
      treatment for panic disorder to other evidence-based psychotherapies are needed,
      and also trials that can separate patient preferences for treatment from
      randomization effects on outcome, disability and healthcare utilization in the
      longer term. METHODS/DESIGN: A phase 2/3 doubly-randomized controlled trial
      carried out in routine care with 216 adults (aged 18 to 70 years) with a primary
      diagnosis of DSM-IV Panic Disorder (with or without Agoraphobia). Within each
      clinic, patients are randomized to self-selection, random assignment of
      treatment, or wait-list. Patients choose or are randomly assigned to either Panic
      Control Treatment or Panic-Focused Psychodynamic Psychotherapy. Primary outcomes
      are changes in panic symptom severity, occupational status, and sickness-related
      absences from work at post-treatment and 6, 12 and 24 months post-treatment.
      Secondary outcomes include changes in agoraphobic avoidance, psychiatric
      comorbidity, disability, and healthcare utilization. The study also employs
      elements of an effectiveness trial as therapist and service-related effects on
      outcome will be estimated. Putative change mechanisms for the two treatments are
      also assessed. DISCUSSION: Cognitive behavioral and psychodynamic therapies are
      both evidence-based approaches that are routinely offered to panic disordered
      patients in Sweden. However, little is known about the relative effectiveness of
      these two approaches for panic/agoraphobia, work-related disability and
      healthcare utilization over the longer term. The current trial (POSE) also
      addresses the important but understudied issue of whether patient preference for
      a particular psychotherapeutic approach moderates outcome. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT01606592 (registered 19 March 2012).

PMID- 25873069
TI  - Regulation of Hypoxia-inducible Factor-1alpha and Vascular Endothelial Growth
      Factor Signaling by Plant Flavonoids.
AB  - Discovery of novel drugs that are able to prevent angiogenesis is a fast growing
      branch of cancer research. Current approaches to cancer chemotherapy include the
      use of alkylating agents, antimetabolites, antitumor antibiotics, platinum
      analogs and drugs derived from natural compounds. However, most of the currently
      used chemotherapeutic drugs have adverse side effects on normal healthy cells. In
      addition to the classical targets of cancer chemotherapy, prevention of
      angiogenesis through the regulation of indigenous angiogenic factors is a leading
      approach of developing selective novel anticancer drugs. Because of their low
      toxicity, there is increasing interest in exploring specific dietary
      phytochemicals as possible antiangiogenic agents. In this mini-review, selected
      flavonoids (e.g., apigenin, luteolin, quercetin and epigallocatechin-3-gallate,
      which are a group of plant polyphenols) that are able to regulate angiogenesis in
      in vitro and in vivo systems are discussed in the light of their potential to be
      exploited as novel anticancer drugs.

PMID- 25873070
TI  - Antitumor activity of pamidronate in breast cancer cells transformed by low doses
      of alpha-particles and estrogen in vitro.
AB  - Human breast cancer is a major cause of global morbidity and mortality in women
      and it is a process that involves numerous molecular and cellular alterations
      attributed to environmental substances and agents such as hormones.
      Bisphosphonates, such as pamidronate, are potent antiresorptive drugs used to the
      treatment of metabolic bone disease, exerting anti-proliferative, anti-migratory
      and apoptotic effects. The aim of this study was to evaluate gene and protein
      expression involved in these processes. An in vitro model was developed with the
      MCF-10F immortalized breast epithelial cell line exposed to low radiation doses
      of high LET (linear energy transfer) alpha-particles (150 keV/um) and cultured in
      the presence of 17beta-estradiol (estrogen). This model consisted of the
      following cell lines: i) MCF-10F, normal; ii) Alpha3, non-malignant; iii) Alpha5,
      pre-tumorigenic, and iv) Tumor2, derived from Alpha5 injected into the nude mice.
      Our previous results have shown that Alpha5 and Tumor2 increased cell
      proliferation, anchorage independency, invasive capabilities and tumor formation
      in nude mice in comparison to control. Expression of the gene (RT-qPCR) and
      protein (western blotting, flow cyto-metry) was measured. The results indicated
      that pamidronate decreased invasion, migration and Rho-A, c-Ha-ras, p53, Serpin
      1, Caveolin-1, Bcl-xL and NFkappaB gene and protein expression. Thus, it seems
      that pamidronate may impinge upon cellular proliferation, invasion, metastasis
      and apoptosis and it may exert antitumor activity in breast cancer cells
      transformed by low doses of alpha-particles and estrogen in vitro.

PMID- 25873071
TI  - Use of non-pharmaceutical interventions to reduce the transmission of influenza
      in adults: A systematic review.
AB  - During seasonal influenza epidemics and pandemics, virus transmission causes
      significant public health concern. Reduction of viral transmission by non
      pharmaceutical interventions (NPI) has a significant appeal and is often
      recommended. However, the efficacy of such interventions is unclear. A systematic
      literature review was undertaken to identify and evaluate the published
      literature on NPI efficacy to prevent human transmission of influenza virus in
      adults. Reviewers assessed the quality of eligible studies utilizing the Critical
      Appraisal Skills Programme for bias and the Scottish Intercollegiate Guidelines
      Network for methodological quality. Studies were assessed for risk of bias
      domains of random sequence generation, allocation concealment, attribution bias,
      selective reporting and blinding. Relevant citations of 2247 were reduced to 100
      for full-text evaluation. Only seven met all selection criteria and pooled
      analysis was not feasible. Of the seven studies, two were randomized controlled
      trials (RCT) and five were cluster RCT. The main NPI studied were disinfection
      and hygiene; barriers; and combined NPI. However, these seven RCT had significant
      design flaws. Only two studies used laboratory confirmed influenza and poor
      statistical power was a major problem. Positive significant interventions
      included professional oral hygiene intervention in the elderly and hand washing.
      Despite the potential for NPI in preventing influenza transmission, there is very
      limited data available. Hand washing and dental hygiene may be useful, but other
      interventions have not been fully assessed. Properly designed studies evaluating
      large populations including 'at risk' patients and in a variety of communities
      are needed. 

PMID- 25873072
TI  - Persuasion to use personal protective equipment in constructing subway stations:
      application of social marketing.
AB  - To study the effects of an intervention based on social marketing to persuade
      workers to use personal protective equipment (PPE) in constructing subway
      stations in Isfahan, Iran. This was a quasi-experimental study. Two stations were
      selected as intervention and control groups. Intervention was designed based on
      results of a formative research. A free package containing a safety helmet with a
      tailored message affixed to it, mask and gloves and an educational pamphlet was
      delivered to the intervention group. After 6 weeks, behaviours in the
      intervention and control stations were measured using an observational checklist.
      After the intervention, the percentage of workers who used PPE at the
      intervention station increased significantly. OR for helmet and mask usage was
      7.009 and 2.235, respectively, in the intervention group. Social marketing can be
      used to persuade workers to use PPE in the workplace. 

PMID- 25873074
TI  - Development of Online Spectroscopic pH Monitoring for Nuclear Fuel Reprocessing
      Plants: Weak Acid Schemes.
AB  - In nuclear fuel reprocessing, separating trivalent minor actinides and lanthanide
      fission products is extremely challenging and often necessitates tight pH control
      in TALSPEAK (Trivalent Actinide-Lanthanide Separation by Phosphorus reagent
      Extraction from Aqueous Komplexes) separations. In TALSPEAK and similar advanced
      processes, aqueous pH is one of the most important factors governing the
      partitioning of lanthanides and actinides between an aqueous phase containing a
      polyaminopolycarboxylate complexing agent and a weak carboxylic acid buffer and
      an organic phase containing an acidic organophosphorus extractant. Real-time pH
      monitoring would significantly increase confidence in the separation performance.
      Our research is focused on developing a general method for online determination
      of the pH of aqueous solutions through chemometric analysis of Raman spectra.
      Spectroscopic process-monitoring capabilities, incorporated in a counter-current
      centrifugal contactor bank, provide a pathway for online, real-time measurement
      of solution pH. The spectroscopic techniques are process-friendly and can be
      easily configured for online applications, whereas classic potentiometric pH
      measurements require frequent calibration/maintenance and have poor long-term
      stability in aggressive chemical and radiation environments. Raman spectroscopy
      discriminates between the protonated and deprotonated forms of the carboxylic
      acid buffer, and the chemometric processing of the Raman spectral data with PLS
      (partial least-squares) regression provides a means to quantify their respective
      abundances and therefore determine the solution pH. Interpretive quantitative
      models have been developed and validated under a range of chemical composition
      and pH conditions using a lactic acid/lactate buffer system. The developed model
      was applied to new spectra obtained from online spectral measurements during a
      solvent extraction experiment using a counter-current centrifugal contactor bank.
      The model predicted the pH of this validation data set within 11% for pH > 2,
      thus demonstrating that this technique could provide the capability of monitoring
      pH online in applications such as nuclear fuel reprocessing. 

PMID- 25873073
TI  - How strict is galactose restriction in adults with galactosaemia? International
      practice.
AB  - Dietary management of 418 adult patients with galactosaemia (from 39 centres/12
      countries) was compared. All centres advised lactose restriction, 6 restricted
      galactose from galactosides +/- fruits and vegetables and 12 offal. 38% (n=15)
      relaxed diet by: 1) allowing traces of lactose in manufactured foods (n=13) or 2)
      giving fruits, vegetables and galactosides (n=2). Only 15% (n=6) calculated
      dietary galactose. 32% of patients were lost to dietetic follow-up. In adult
      galactosaemia, there is limited diet relaxation.

PMID- 25873075
TI  - Cu(I)/TF-BiphamPhos-catalyzed asymmetric Michael addition of cyclic ketimino
      esters to alkylidene malonates.
AB  - Cu(I)-catalyzed asymmetric Michael addition of cyclic ketimino esters with
      alkylidene malonates has been developed for efficient construction of beta
      branched alpha-amino acids containing adjacent quaternary and tertiary
      stereogenic centers in good yields with excellent diastereo
      /enantioselectivities. The generated Michael adduct was further converted to the
      biologically important pyrrolizidine analogues via one-pot sequential
      reduction/lactamization.

PMID- 25873076
TI  - Few comply with clinical trials reporting law.
AB  - The Food and Drug Administration Amendments Act requires researchers to submit
      clinical trial results to ClinicalTrials.gov within a year of completion.
      However, a new study indicates that only 13.4% of trials comply. 

PMID- 25873077
TI  - Germline Mutations in the CDKN2B Tumor Suppressor Gene Predispose to Renal Cell
      Carcinoma.
AB  - Familial renal cell carcinoma (RCC) is genetically heterogeneous and may be
      caused by mutations in multiple genes, including VHL, MET, SDHB, FH, FLCN, PTEN,
      and BAP1. However, most individuals with inherited RCC do not have a detectable
      germline mutation. To identify novel inherited RCC genes, we undertook exome
      resequencing studies in a familial RCC kindred and identified a CDKN2B nonsense
      mutation that segregated with familial RCC status. Targeted resequencing of
      CDKN2B in individuals (n = 82) with features of inherited RCC then revealed three
      candidate CDKN2B missense mutations (p.Pro40Thr, p.Ala23Glu, and p.Asp86Asn). In
      silico analysis of the three-dimensional structures indicated that each missense
      substitution was likely pathogenic through reduced stability of the mutant or
      reduced affinity for cyclin-dependent kinases 4 and 6, and in vitro studies
      demonstrated that each of the mutations impaired CDKN2B-induced suppression of
      proliferation in an RCC cell line. These findings identify germline CDKN2B
      mutations as a novel cause of familial RCC. SIGNIFICANCE: Germline loss-of
      function CDKN2B mutations were identified in a subset of patients with features
      of inherited RCC. Detection of germline CDKN2B mutations will have an impact on
      familial cancer screening and might prove to influence the management of
      disseminated disease.

PMID- 25873079
TI  - Bioinformatics, interaction network analysis, and neural networks to characterize
      gene expression of radicular cyst and periapical granuloma.
AB  - INTRODUCTION: Bioinformatics has emerged as an important tool to analyze the
      large amount of data generated by research in different diseases. In this study,
      gene expression for radicular cysts (RCs) and periapical granulomas (PGs) was
      characterized based on a leader gene approach. METHODS: A validated
      bioinformatics algorithm was applied to identify leader genes for RCs and PGs.
      Genes related to RCs and PGs were first identified in PubMed, GenBank, GeneAtlas,
      and GeneCards databases. The Web-available STRING software (The European
      Molecular Biology Laboratory [EMBL], Heidelberg, Baden-Wurttemberg, Germany) was
      used in order to build the interaction map among the identified genes by a
      significance score named weighted number of links. Based on the weighted number
      of links, genes were clustered using k-means. The genes in the highest cluster
      were considered leader genes. Multilayer perceptron neural network analysis was
      used as a complementary supplement for gene classification. RESULTS: For RCs, the
      suggested leader genes were TP53 and EP300, whereas PGs were associated with
      IL2RG, CCL2, CCL4, CCL5, CCR1, CCR3, and CCR5 genes. CONCLUSIONS: Our data
      revealed different gene expression for RCs and PGs, suggesting that not only the
      inflammatory nature but also other biological processes might differentiate RCs
      and PGs.

PMID- 25873080
TI  - Inter-Institutional Pathology Consultation: The Importance of Breast Pathology
      Subspecialization in a Setting of Tertiary Cancer Center.
AB  - Inter-institutional pathology consultation (IPC) has shown to be significant in
      patient care. The purpose of the study was to evaluate the impact of IPC for
      breast biopsies in our institution. A total of 502 consecutive consult cases of
      breast core needle biopsies were reviewed. The original pathology reports from
      the referring institutions and our reports were compared for all cases. All cases
      were reviewed by specialized breast pathologists. Discordance was divided into
      minor and major based on the impact on patient care. We reviewed the subsequent
      excisional biopsy for all discordant cases. Discordance was seen in 104 (20.7%)
      cases; 40 (8%) had a major discordance and 64 (13%) had a minor discordance.
      Subsequent surgical excision was available for 25 (62.5%) cases with major
      discordance and for 13 (20.3%) with minor discordance. Our interpretation changed
      management in 15 (3%) patients, while 25 (5%) had a potential of management
      change. The cases with major discordance could be subcategorized into five
      groups, malignant 5 (12.5%), premalignant 16 (40%), biomarkers 10 (25%),
      fibroepithelial lesions 6 (15%), and others 3 (7.5%). Our findings support the
      value of IPC review in decreasing the likelihood of diagnostic errors that may
      lead to significant impact on patient care. It is necessary that outside
      pathology material in the referral settings been reviewed by a specialized breast
      pathologist. 

PMID- 25873078
TI  - Nonalcoholic fatty liver disease: update on pathogenesis, diagnosis, treatment
      and the role of S-adenosylmethionine.
AB  - Nonalcoholic fatty liver disease (NAFLD) is currently the most common liver
      disease worldwide affecting over one-third of the population in the U.S. It has
      been associated with obesity, type 2 diabetes, hyperlipidemia, and insulin
      resistance and is initiated by the accumulation of triglycerides in hepatocytes.
      Isolated hepatic steatosis (IHS) remains a benign process, while a subset
      develops superimposed inflammatory activity and progression to nonalcoholic
      steatohepatitis (NASH) with or without fibrosis. However, the molecular
      mechanisms underlying NAFLD progression are not completely understood. Liver
      biopsy is still required to differentiate IHS from NASH as easily accessible
      noninvasive biomarkers are lacking. In terms of treatments for NASH,
      pioglitazone, vitamin E, and obeticholic acid have shown some benefit. All of
      these agents have potential complications associated with long-term use.
      Nowadays, a complex hypothesis suggests that multiple parallel hits are involved
      in NASH development. However, the 'key switch' between IHS and NASH remains to be
      discovered. We have recently shown that knocking out enzymes involved in S
      adenosylmethionine (SAMe) metabolism, the main biological methyl donor in humans
      that is abundant in the liver, will lead to NASH development in mice. This could
      be due to the fact that a normal SAMe level is required to establish the proper
      ratio of phosphatidylethanolamine to phosphatidylcholine that has been found to
      be important in NAFLD progression. New data from humans have also suggested that
      these enzymes play a role in the pathogenesis of NAFLD and that some of SAMe
      cycle metabolites may serve as noninvasive biomarkers of NASH. In this review, we
      discuss the evidence of the role of SAMe in animal models and humans with NAFLD
      and how studying this area may lead to the discovery of new noninvasive
      biomarkers and possibly personalized treatment for NASH.

PMID- 25873082
TI  - Promotion of Proapoptotic Signals by Lysosomal Photodamage.
AB  - We previously reported that low-level lysosomal photodamage enhanced the efficacy
      of subsequent mitochondrial photodamage, resulting in a substantial promotion of
      apoptotic cell death. We now extend our analysis of the sequential PDT protocol
      to include two additional lysosomal-targeting photosensitizers. These agents,
      because of enhanced permeability, are more potent than the agent (N-aspartyl
      chlorin E6, NPe6) used in the initial study. Addition of the cell-permeable
      cysteine protease inhibitor E-64d and calcium chelator BAPTA-AM almost completely
      suppressed sequential PDT-induced loss of mitochondrial membrane potential and
      activation of procaspases-3 and -7. These inhibitors did not, however, suppress
      the proapoptotic effect of a BH3 mimetic or mitochondrial photodamage. Knockdowns
      of ATG7 or ATG5, proteins normally associated with autophagy, suppressed
      photodamage induced by the sequential PDT protocol. These effects appear to be
      independent of the autophagic process as pharmacological inhibition of autophagy
      offered no such protection. Effects of ATG7 and ATG5 knockdowns may reflect the
      role that ATG7 plays in regulating lysosome permeability, and the likelihood that
      a proteolytic fragment of ATG5 amplifies mitochondrial proapoptotic processes.
      Our results suggest that low-dose photodamage that sequentially targets lysosomes
      and mitochondria may offer significant advantages over the use of single
      photosensitizers. 

PMID- 25873083
TI  - Declining newborn intramuscular vitamin K prophylaxis predicts subsequent
      immunisation refusal: A retrospective cohort study.
AB  - AIM: Low rates of childhood immunisation are linked to outbreaks of infectious
      disease. Identifying and addressing barriers to immunisation may lead to improved
      immunisation rates. Immunisation and newborn vitamin K prophylaxis have many
      similarities. We aimed to investigate whether parents who decline newborn vitamin
      K are also more likely to decline subsequent childhood immunisations. METHODS: We
      undertook a retrospective cohort study, examining the relationship between
      vitamin K administration and immunisation uptake by parents of babies born over a
      2-year period (January 2010-December 2011) in Dunedin, New Zealand (NZ). Both
      written and electronic data from a single birthing unit and the NZ National
      Immunisation Register (NIR) were analysed to ascertain the relationship between
      declining newborn vitamin K prophylaxis and subsequent immunisation uptake.
      RESULTS: Records for 3575 babies were examined. Ninety-two per cent of infants
      received intramuscular, and 5% received oral vitamin K. An increased risk ratio
      for non-immunisation of 14.1 (95% confidence interval 7.8-25.9) for babies whose
      parents declined vitamin K was identified. Receiving oral vitamin K was also
      associated with subsequent non-immunisation, with a risk ratio of 3.5 (95%
      confidence interval 1.7-7.3). CONCLUSIONS: Parents who decline newborn vitamin K
      are more likely to decline immunisation for their child. These parents, as well
      as those that elect for oral vitamin K, are a small but easily identifiable group
      to whom additional education about the benefits of immunisation could be offered.
      This is especially pertinent at a time when there is a resurgence of immunisation
      preventable diseases.

PMID- 25873084
TI  - Animal, but not human, faces engage the distributed face network in adolescents
      with autism.
AB  - Multiple hypotheses have been offered to explain the impaired face-processing
      behavior and the accompanying underlying disruptions in neural circuitry among
      individuals with autism. We explored the specificity of atypical face-processing
      activation and potential alterations to fusiform gyrus (FG) morphology as
      potential underlying mechanisms. Adolescents with high functioning autism (HFA)
      and age-matched typically developing (TD) adolescents were scanned with sMRI and
      fMRI as they observed human and animal faces. In spite of exhibiting comparable
      face recognition behavior, the HFA adolescents evinced hypo-activation throughout
      the face-processing system in response to unfamiliar human, but not animal,
      faces. They also exhibited greater activation in affective regions of the face
      processing network in response to animal, but not human, faces. Importantly, this
      atypical pattern of activation in response to human faces was not related to
      atypical structural properties of the FG. This atypical neural response to human
      faces in autism may stem from abnormalities in the ability to represent the
      reward value of social (i.e. conspecific) stimuli. 

PMID- 25873085
TI  - Cisplatin binding to human serum albumin: a structural study.
AB  - The reaction between cisplatin and human serum albumin (HSA) was investigated by
      X-ray crystallography and crystal structures of the cisplatin/HSA adduct were
      eventually solved for the first time. Structural data unambiguously prove that
      cisplatin mainly binds to His105 and Met329 side chains; additional binding sites
      are detected at His288, Met298, and Met548 and at His535, His67 and His247. 

PMID- 25873086
TI  - Superiority of [68Ga]-DOTATATE PET/CT to Other Functional Imaging Modalities in
      the Localization of SDHB-Associated Metastatic Pheochromocytoma and
      Paraganglioma.
AB  - PURPOSE: Patients with succinate dehydrogenase subunit B(SDHB) mutation-related
      pheochromocytoma/paraganglioma (PHEO/PGL) are at a higher risk for metastatic
      disease than other hereditary PHEOs/PGLs. Current therapeutic approaches are
      limited, but the best outcomes are based on the early and proper detection of as
      many lesions as possible. Because PHEOs/PGLs overexpress somatostatin receptor 2
      (SSTR2), the goal of our study was to assess the clinical utility of [(68)Ga]
      DOTA(0)-Tyr(3)-octreotate ([(68)Ga]-DOTATATE) positron emission
      tomography/computed tomography (PET/CT) and to evaluate its diagnostic utility in
      comparison with the currently recommended functional imaging modalities [(18)F]
      fluorodopamine ([(18)F]-FDA), [(18)F]-fluorodihydroxyphenylalanine ([(18)F]
      FDOPA), [(18)F]-fluoro-2-deoxy-d-glucose ([(18)F]- FDG) PET/CT as well as CT/MRI.
      EXPERIMENTAL DESIGN: [(68)Ga]-DOTATATE PET/CT was prospectively performed in 17
      patients with SDHB-related metastatic PHEOs/PGLs. All patients also underwent
      [(18)F]-FDG PET/CT and CT/MRI, with 16 of the 17 patients also receiving [(18)F]
      FDOPA and [(18)F]-FDA PET/CT scans. Detection rates of metastatic lesions were
      compared between all these functional imaging studies. A composite synthesis of
      all used functional and anatomical imaging studies served as the imaging
      comparator. RESULTS: [(68)Ga]-DOTATATE PET/CT demonstrated a lesion-based
      detection rate of 98.6% [95% confidence interval (CI), 96.5%-99.5%], [(18)F]-FDG,
      [(18)F]-FDOPA, [(18)F]-FDA PET/CT, and CT/MRI showed detection rates of 85.8%
      (CI, 81.3%-89.4%; P < 0.01), 61.4% (CI, 55.6%-66.9%; P < 0.01), 51.9% (CI, 46.1%
      57.7%; P < 0.01), and 84.8% (CI, 80.0%-88.5%; P < 0.01), respectively.
      CONCLUSIONS: [(68)Ga]-DOTATATE PET/CT showed a significantly superior detection
      rate to all other functional and anatomical imaging modalities and may represent
      the preferred future imaging modality in the evaluation of SDHB-related
      metastatic PHEO/PGL.

PMID- 25873088
TI  - PPARD +294C overrepresentation in general and long-lived population in China Bama
      longevity area and unique relationships between PPARD +294T/C polymorphism and
      serum lipid profiles.
AB  - BACKGROUND: The +294T/C polymorphism in the peroxisome proliferator-activated
      receptor delta (PPARD) gene is associated with hyperlipidemia in several younger
      populations, but results are still inconsistence across ethnic groups and its
      possible impact on the lipid profiles of long-lived individuals remains
      unexploited. Here, we aimed to evaluate the possible correlation between PPARD
      +294T/C and serum lipid levels in a long-lived population in Bama, a region known
      for longevity situated in Guangxi, China. METHODS: Genotyping of PPARD +294T/C
      polymorphism was conducted in 505 long-lived inhabitants (aged 90 and above, long
      lived group, LG) and 468 healthy controls (aged 60-75, non-long-lived group, non
      LG) recruited from Bama area. RESULTS: No difference in allelic and genotypic
      frequencies was found between the two groups (P>0.05). However, C-allele and C
      genotype (TC and CC) were significantly more frequent in the females of non-LG
      than were LG after sex stratification. CC carriers exhibited higher LDL-C level
      in LG (P<0.05) but lower TC, TG and LDL-C in non-LG (P<0.05 for each) than TT
      carriers; C allele carriers (TC/CC) in LG exhibited higher TC, TG, and LDL-C
      levels as compared with the same genotype and the same lipid parameter in non-LG
      (P<0.05 for each). LDL-C in LG was correlated with genotypes while TC, TG, and
      LDL-C in non-LG were correlated with genotypes (P<0.05-0.001). CONCLUSION: Our
      results suggest that there were different impact patterns of PPARD +294T/C
      polymorphism on lipid profiles between long-lived cohort and average population
      in Bama area and this may be one of the genetic bases of its longevity.

PMID- 25873087
TI  - Analyses of 7,635 Patients with Colorectal Cancer Using Independent Training and
      Validation Cohorts Show That rs9929218 in CDH1 Is a Prognostic Marker of
      Survival.
AB  - PURPOSE: Genome-wide association studies have identified numerous loci associated
      with colorectal cancer risk. Several of these have also been associated with
      patient survival, although none have been validated. Here, we used large
      independent training and validation cohorts to identify robust prognostic
      biomarkers for colorectal cancer. EXPERIMENTAL DESIGN: In our training phase, we
      analyzed 20 colorectal cancer-risk SNPs from 14 genome-wide associated loci, for
      their effects on survival in 2,083 patients with advanced colorectal cancer. A
      Cox survival model was used, stratified for treatment, adjusted for known
      prognostic factors, and corrected for multiple testing. Three SNPs were
      subsequently analyzed in an independent validation cohort of 5,552 colorectal
      cancer patients. A validated SNP was analyzed by disease stage and response to
      treatment. RESULTS: Three variants associated with survival in the training
      phase; however, only rs9929218 at 16q22 (intron 2 of CDH1, encoding E-cadherin)
      was significant in the validation phase. Patients homozygous for the minor allele
      (AA genotype) had worse survival (training phase HR, 1.43; 95% confidence
      intervals; CI, 1.20-1.71, P = 5.8 * 10(-5); validation phase HR, 1.18; 95% CI,
      1.01-1.37, P = 3.2 * 10(-2); combined HR, 1.28; 95% CI, 1.14-1.43, P = 2.2 * 10(
      5)). This effect was independent of known prognostic factors, and was significant
      amongst patients with stage IV disease (P = 2.7 * 10(-5)). rs9929218 was also
      associated with poor response to chemotherapy (P = 3.9 * 10(-4)). CONCLUSIONS: We
      demonstrate the potential of common inherited genetic variants to inform patient
      outcome and show that rs9929218 identifies approximately 8% of colorectal cancer
      patients with poor prognosis. rs9929218 may affect CDH1 expression and E-cadherin
      plays a role in epithelial-to-mesenchymal transition providing a mechanism
      underlying its prognostic potential. Clin Cancer Res; 21(15); 3453-61. (c)2015
      AACR.

PMID- 25873089
TI  - The AvecNet Trial to assess whether addition of pyriproxyfen, an insect juvenile
      hormone mimic, to long-lasting insecticidal mosquito nets provides additional
      protection against clinical malaria over current best practice in an area with
      pyrethroid-resistant vectors in rural Burkina Faso: study protocol for a
      randomised controlled trial.
AB  - BACKGROUND: Recent reductions in malaria in sub-Saharan Africa have been
      associated with increased coverage with long-lasting insecticidal nets (LLINs).
      Pyrethroids are currently the only insecticide class used for treating nets, and
      the rapid increase in resistance to pyrethroids in vector mosquitoes may
      jeopardise future vector control. Nets containing a novel combination of
      permethrin, a pyrethroid, and pyriproxyfen, an insect juvenile hormone mimic,
      (PPF-LLIN) may enhance malaria control, as well as reducing the spread of
      pyrethroid-resistant mosquitoes. This trial will determine whether PPF-LLINs
      provide incremental protection against malaria over current best practice of
      LLINs and prompt treatment in an area with pyrethroid-resistant vectors. METHODS:
      A 2 armed cluster-randomised controlled trial will be conducted in Burkina Faso
      to assess whether PPF-LLIN (containing 2% permethrin and 1% pyriproxyfen w/w)
      provide better protection against clinical malaria in children than 2% permethrin
      treated LLINs. Study subjects will be recruited and provided with LLINs at the
      start of the study. The LLINs will be exchanged for PPF-LLIN by cluster in a step
      wedge fashion so 3 months before the end of the 2 year trial all participants
      will have a PPF-LLIN. The primary endpoint will be clinical malaria incidence
      measured by passive case detection in a cohort of children, aged 6 months to 5
      years. Anaemia and parasite prevalence will also be measured in children during
      cross-sectional surveys. Exposure to malaria parasites will be assessed using
      light traps followed by identification of common vector species and their
      sporozoite infection rates. Safety evaluation will include recording of adverse
      events and pregnancy outcomes. The main endpoint analysis will include adjusting
      for distance between village clusters with different types of nets, as the impact
      of PPF-LLIN is likely to increase as larger areas are dominated by PPF-LLIN,
      reducing the spill over of mosquitoes from villages with LLINs. DISCUSSION: The
      step-wedge design is to measure the impact of an incrementally delivered
      environmental intervention where we expect the degree of control to be improved
      as more people use PPF-LLIN over a larger area. Trial findings will help inform
      policy makers on the effectiveness of PPF-LLIN nets for malaria control in areas
      of pyrethroid resistance. TRIAL REGISTRATION: ISRCTN21853394 - AvecNet,
      registered on 3 April 2013.

PMID- 25873091
TI  - Results of all clinical trials should be posted within a year, says WHO.

PMID- 25873090
TI  - Cognitive behavioral therapy for adults with attention-deficit hyperactivity
      disorder: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is a mental disorder
      beginning in childhood, and about half of patients have symptoms lasting into
      adulthood. Adult ADHD causes various impairments of emotional, self-esteem, and
      executive function and life quality aspects. Furthermore, adverse outcomes
      include academic and occupational failures, traffic accidents and substance
      abuse, which would be a family and social burden. A combination of medication and
      psychotherapy is recommended as the treatment for adult ADHD, and cognitive
      behavioral therapy (CBT) has been validated mostly with evidence-based
      researches. However, there has been a lack of randomized controlled trials of CBT
      for patients in China. Moreover, booster sessions of CBT for other disorders have
      proven effective in reducing recurrence and improving long-term outcomes, which
      has not been investigated for adult ADHD. This study will testify to the effect
      of CBT and explore the efficacy of subsequent booster sessions on adult ADHD.
      METHODS/DESIGN: It is a three-armed randomized controlled trial to evaluate the
      efficacy of 12 weeks of CBT based on the published and validated manual and its
      booster sessions. The 12 weeks of CBT will be conducted weekly and will end at
      the 12th week, and then the booster sessions will be conducted monthly and end at
      the 24th week. There are three randomized groups, including a CBT with booster
      sessions group, a CBT group and a waiting group. Participants are outpatients of
      the Peking University Sixth Hospital who are diagnosed as having adult ADHD. The
      Primary efficacy endpoints are the scores of ADHD core symptoms at 12 and 24
      weeks. Secondary endpoints include emotion, executive function, self-esteem, life
      quality and functional magnetic resonance imaging (fMRI) data at different time
      points, and the change within every group will also be analyzed. DISCUSSION: This
      is the first study to explore the efficacy of booster sessions of CBT in adult
      ADHD as far as we know. The results might increase proof of efficacy of CBT for
      adult ADHD in China, and the results showing efficacy of the booster sessions
      would also benefit our clinical practice. TRIAL REGISTRATION: Current Controlled
      Trials: NCT02062411, date of registration: 12 February 2014.

PMID- 25873092
TI  - Electroacupuncture inhibits chronification of the acute pain of knee
      osteoarthritis: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Previous studies have shown that electroacupuncture (EA) has a
      significant effect on acute pain, but it has not solved the clinical problem of
      the chronification of acute pain. Diffuse noxious inhibitory controls (DNIC)
      function as a reliable indicator to predict the risk of chronic pain events. DNIC
      function in knee osteoarthritis (KOA) patients has been demonstrated to gradually
      decrease during the development of chronic pain. The purpose of this study is to
      conduct a randomized, controlled clinical trial to determine if EA can repair
      impaired DNIC function and thus prevent chronification of the acute pain of KOA.
      METHODS/DESIGN: This is a multicenter, single blind, randomized, controlled,
      three-arm, large-scale clinical trial. A total of 450 KOA patients will be
      randomly assigned to three groups. The strong EA group will receive EA with high
      intensity current (2 mA < current < 5 mA) at the ipsilateral 'Neixiyan' (EX-LE5),
      'Dubi'(ST35), 'Liangqiu'(ST34) and 'Xuehai' (SP10). The weak EA group will
      receive EA with low-intensity current (0 mA < current < 0.5 mA) on the same
      acupoints. The sham EA group will receive EA with low-intensity current (0 mA <
      current < 0.5 mA) with fine needles inserted superficially into the sites 2 cm
      lateral to the above acupoints. The patients will be treated with EA once a day,
      30 minutes per session, in 5 sessions per week, for 2 weeks. In order to
      determine the best stage of KOA for effective EA intervention, patients within
      the treatment groups also will be divided into four stages. The primary outcomes
      are Visual Analog Scale (VAS), DNIC function and the Western Ontario and McMaster
      Universities Osteoarthritis Index (WOMAC). Clinical assessments will be evaluated
      at baseline (before treatment) and after 5 to 10 sessions of treatment.
      DISCUSSION: This trial will be helpful in identifying whether strong EA is more
      effective than weak EA in reversing chronification of acute pain through
      repairing the impaired DNIC function and in screening for the best stage of KOA
      for effective EA intervention. TRIAL REGISTRATION: Chinese Clinical Trial
      Registry Number: ChiCTR-ICR-14005411. The date of registration is 31 October
      2014.

PMID- 25873093
TI  - Evaluating the effect of innovative motivation and supervision approaches on
      community health worker performance and retention in Uganda and Mozambique: study
      protocol for a randomised controlled trial.
AB  - BACKGROUND: If trained, equipped and utilised, community health workers (CHWs)
      delivering integrated community case management for sick children can potentially
      reduce child deaths by 60%. However, it is essential to maintain CHW motivation
      and performance. The inSCALE project aims to evaluate, using a cluster randomised
      controlled trial, the effect of interventions to increase CHW supervision and
      performance on the coverage of appropriate treatment for children with diarrhoea,
      pneumonia and malaria. METHODS/DESIGN: Participatory methods were used to
      identify best practices and innovative solutions. Quantitative community based
      baseline surveys were conducted to allow restricted randomisation of clusters
      into intervention and control arms. Individual informed consent was obtained from
      all respondents. Following formative research and stakeholder consultations, two
      intervention packages were developed in Uganda and one in Mozambique. In Uganda,
      approximately 3,500 CHWs in 39 clusters were randomised into a mobile health
      (mHealth) arm, a participatory community engagement arm and a control arm. In
      Mozambique, 275 CHWs in 12 clusters were randomised into a mHealth arm and a
      control arm. The mHealth interventions encompass three components: 1) free phone
      communication between users; 2) data submission using phones with automated
      feedback, messages to supervisors for targeted supervision, and online data
      access for district statisticians; and 3) motivational messages. The community
      engagement arm in Uganda established village health clubs seeking to 1) improve
      the status and standing of CHWs, 2) increase demand for health services and 3)
      communicate that CHWs' work is important. Process evaluation was conducted after
      10 months and end-line surveys will establish impact after 12 months in Uganda
      and 18 months in Mozambique. Main outcomes include proportion of sick children
      appropriately treated, CHW performance and motivation, and cost effectiveness of
      interventions. DISCUSSION: Study strengths include a user-centred design to the
      innovations, while weaknesses include the lack of a robust measurement of
      coverage of appropriate treatment. Evidence of cost-effective innovations that
      increase motivation and performance of CHWs can potentially increase sustainable
      coverage of iCCM at scale. TRIAL REGISTRATION: (identifier NCT01972321 ) on 22
      April 22 2013.

PMID- 25873094
TI  - Changing prognostic significance of tumor stage and nodal stage in patients with
      squamous cell carcinoma of the oropharynx in the human papillomavirus era.
AB  - BACKGROUND: Although human papillomavirus (HPV)-associated oropharyngeal squamous
      cell carcinoma (OPSCC) tends to present at an advanced nodal stage (N stage), the
      prognosis is generally better than that for HPV-negative OPSCC. Prior work has
      demonstrated the increasing incidence of HPV-related OPSCC in the United States.
      This study was designed to determine whether the changing epidemiology of OPSCC
      is reflected in changes in the prognostic significance of the tumor stage (T
      stage) and the N stage in a population-based cohort. METHODS: The Surveillance,
      Epidemiology, and End Results program was used to identify 13,328 patients who
      were 18 years old or older and were diagnosed with OPSCC from 1997 to 2008. The
      Kaplan-Meier method was used to estimate head and neck cancer-specific survival.
      Cox proportional hazards models were used to evaluate the associations between
      head and neck cancer-specific mortality (HNCSM) and T and N stages and the
      interaction of variables with the year of diagnosis. RESULTS: With a median
      follow-up of 67 months, there were 4099 head and neck cancer deaths. There was a
      significant interaction between the T stage and time (P for interaction = .01),
      with the effect of the T stage on HNCSM increasing from 1997 to 2008. The T stage
      retained a linear relationship with HNCSM. The effect of the N stage on HNCSM
      declined over time (P for interaction = .0004). The current American Joint
      Committee on Cancer (AJCC) staging system did not subdivide distinct prognostic
      subgroups for HNCSM by overall stage. CONCLUSIONS: In this population-based study
      of OPSCC, the effect of the N stage on cancer-specific mortality decreased over
      time as the impact of the T stage increased. The current AJCC staging system did
      not distinguish prognostic subgroups. These changes may reflect the increasing
      prevalence of HPV-related OPSCC. Further study in HPV-defined cohorts is needed
      to tailor the AJCC staging system to better reflect HNCSM risk. Cancer
      2015;121:2594-2602. (c) 2015 American Cancer Society.

PMID- 25873095
TI  - Staff's views on delivering patient-led therapy during inpatient stroke
      rehabilitation: a focus group study with lessons for trial fidelity.
AB  - BACKGROUND: Fidelity to the treatment protocol is key to successful trials but
      often problematic. This article reports the staff's views on delivering a complex
      rehabilitation intervention: patient-led therapy during inpatient stroke care.
      METHODS: An exploratory qualitative study using focus groups with staff involved
      in a multicenter (n = 12) feasibility trial of patient-led therapy (the MAESTRO
      trial) was undertaken as part of the evaluation process. Purposive sampling
      ensured that participants represented all recruiting sites, relevant professions
      and levels of seniority. Data analysis used a Framework Approach. RESULTS: Five
      focus groups were held involving 30 participants. Five main themes emerged: the
      effect of the interventions, practical problems, patient-related factors,
      professional dilemmas, and skills. Staff felt the main effect of the therapies
      was on patients' autonomy and occupation; the main practical problems were the
      patients' difficulties in achieving the correct position and a lack of space.
      Staff clearly identified characteristics that made patient-led therapy unsuitable
      for some patients. Most staff experienced dilemmas over how to prioritize the
      trial interventions compared to their usual therapy and other clinical demands.
      Staff also lacked confidence about how to deliver the interventions, particularly
      when adapting the interventions to individual needs. For each barrier to
      implementation, possible solutions were identified. Of these, involving other
      people and establishing a routine were the most common. CONCLUSIONS: Delivering
      rehabilitation interventions within a trial is complex. Staff require time and
      support to develop the skills, strategies and confidence to identify suitable
      patients, deliver new treatments, adapt the new treatments to individuals' needs
      and balance the demands of delivering the trial intervention according to the
      treatment protocol with other clinical and professional priorities. TRIAL
      REGISTRATION:  ISRCTN: ISRCTN29533052 . October 2011.

PMID- 25873096
TI  - A simple technique to identify key recruitment issues in randomised controlled
      trials: Q-QAT - Quanti-Qualitative Appointment Timing.
AB  - BACKGROUND: Recruitment to pragmatic randomised controlled trials (RCTs) is
      acknowledged to be difficult, and few interventions have proved to be effective.
      Previous qualitative research has consistently revealed that recruiters provide
      imbalanced information about RCT treatments. However, qualitative research can be
      time-consuming to apply. Within a programme of research to optimise recruitment
      and informed consent in challenging RCTs, we developed a simple technique, Q-QAT
      (Quanti-Qualitative Appointment Timing), to systematically investigate and
      quantify the imbalance to help identify and address recruitment difficulties.
      METHODS: The Q-QAT technique comprised: 1) quantification of time spent
      discussing the RCT and its treatments using transcripts of audio-recorded
      recruitment appointments, 2) targeted qualitative research to understand the
      obstacles to recruitment and 3) feedback to recruiters on opportunities for
      improvement. This was applied to two RCTs with different clinical contexts and
      recruitment processes. Comparisons were made across clinical centres, recruiters
      and specialties. RESULTS: In both RCTs, the Q-QAT technique first identified
      considerable variations in the time spent by recruiters discussing the RCT and
      its treatments. The patterns emerging from this initial quantification of
      recruitment appointments then enabled targeted qualitative research to understand
      the issues and make suggestions to improve recruitment. In RCT1, presentation of
      the treatments was balanced, but little time was devoted to describing the RCT.
      Qualitative research revealed patients would have considered participation, but
      lacked awareness of the RCT. In RCT2, the balance of treatment presentation
      varied by specialists and centres. Qualitative research revealed difficulties
      with equipoise and confidence among recruiters presenting the RCT. The
      quantitative and qualitative findings were well-received by recruiters and
      opportunities to improve information provision were discussed. A blind coding
      exercise across three researchers led to the development of guidelines that can
      be used to apply the Q-QAT technique to other difficult RCTs. CONCLUSION: The Q
      QAT technique was easy to apply and rapidly identified obstacles to recruitment
      that could be understood through targeted qualitative research and addressed
      through feedback. The technique's combination of quantitative and qualitative
      findings enabled the presentation of a holistic picture of recruitment challenges
      and added credibility to the feedback process. Note: both RCTs in this manuscript
      asked to be anonymised, so no trial registration details are provided.

PMID- 25873097
TI  - Hypertension management in primary care: study protocol for a cluster randomized
      controlled trial.
AB  - BACKGROUND: Studies worldwide show insufficient blood pressure control rates, and
      effective management of hypertension remains a challenge in general practice.
      Although structured forms of care improved blood pressure in randomized
      controlled trials, little is known about their effects under routine primary
      care. This cluster randomized trial (CRT) evaluates the effects of a modern
      interactive medical education series for general practitioners on hypertension
      management, including practice redesign strategies. METHODS/DESIGN: For this CRT,
      24 primary care academic teaching practices of the University of Duisburg-Essen,
      Germany, are randomized into two study arms. With the objective of improving
      hypertension control, general practitioners of the intervention group participate
      in a three-session medical education program on structured hypertension
      management. The program aims at changing physician awareness and practice design.
      Various practice tools are provided: for example, checklists on valid blood
      pressure readings, medication selection, detection of secondary hypertension, and
      patient education. General practitioners of both study groups include
      hypertensive patients with and without hypertension-related diseases such as
      angiographically proven coronary disease, and peripheral or cerebral vascular
      disease. Blood pressure is measured by 24-hour readings. Analyses will focus on
      differences in blood pressure control and changes of practice management between
      intervention and control group. DISCUSSION: The study will determine the
      effectiveness of our practice redesign intervention on hypertension control. The
      intervention addresses general practitioners and practice assistants, while
      aiming at benefits on the patient level. Therefore, the cluster design is used to
      evaluate the effects. TRIAL REGISTRATION: DRKS00006315 (date of registration: 14
      July 2014).

PMID- 25873098
TI  - From imported to an endemic disease: impact of Chikungunya virus disease in the
      hospital epidemiology, Tolima, Colombia, 2014-2015.

PMID- 25873099
TI  - Leptospirosis in an urban setting: cases diagnosed at a private medical center of
      Western Colombia, 2008-2012.
AB  - INTRODUCTION: Leptospirosis has reemerged as significant threat particularly in
      developing countries, including those in Latin America. Data from Colombia is
      still limited and there are no published studies in the Western area of the
      country. METHODS: Data on suspected cases were collected over the study period
      (2008- 2012). Cases were diagnosed clinically and confirmed by ELISA IgG and
      microscopic agglutination test (MAT) (titers >=1:400). RESULTS: During the study
      period 264 suspected cases of leptospirosis were found. From those, 8.33% (22
      cases) were microbiologically confirmed. Number of suspected cases increased in
      the period from 20 (2008) (40 cases/100,000 consultations) to 58 (2012) (120
      cases/100,000 consultations). Regard sex distribution, 62.5% were males, 14% in
      the age group 21-30 y-old, from confirmed cases 95% live in urban areas of
      Pereira, 25.7% own dogs and 13.2% cats, 32.3% reporting rats at home as well
      22.7% at work places. From confirmed cases 72.7% were hospitalized. Clinical
      findings found were: fever (60.2%), myalgias (47%), and headache (41.9%), among
      others. All the cases corresponded to Leptospira interrogans. Regard the
      serovars, in these patients 6 were identified: Australis (54.5%),
      Icterohaemorrhagiae (45.5%), Canicola (45.5%), Panama (45.5%), Pomona (36.3) and
      Grippotyphosa (1%). Thirty nine percent of the patients received antimicrobial
      therapy, 50% ceftriaxone. No deaths occurred. CONCLUSION: Leptospirosis is an
      emerging infectious disease that has changed from an occupational disease of
      veterinarians, farmers, butchers, and other animal handlers to a cause of
      epidemics in poor and decayed urban communities in developing countries,
      including those in Latin America such as Colombia.

PMID- 25873102
TI  - Car parking is a clinical quality issue.

PMID- 25873100
TI  - Donor CD4 T Cell Diversity Determines Virus Reactivation in Patients After HLA
      Matched Allogeneic Stem Cell Transplantation.
AB  - Delayed reconstitution of the T cell compartment in recipients of allogeneic stem
      cell grafts is associated with an increase of reactivation of latent viruses.
      Thereby, the transplanted T cell repertoire appears to be one of the factors that
      affect T cell reconstitution. Therefore, we studied the T cell receptor beta
      (TCRbeta) gene rearrangements of flow cytometry-sorted CD4(+) and CD8(+) T cells
      from the peripheral blood of 23 allogeneic donors before G-CSF administration and
      on the day of apheresis. For this purpose, TCRbeta rearrangements were amplified
      by multiplex PCR followed by high-throughput amplicon sequencing. Overall, CD4(+)
      T cells displayed a significantly higher TCRbeta diversity compared to CD8(+) T
      cells irrespective of G-CSF administration. In line, no significant impact of G
      CSF treatment on the TCR Vbeta repertoire usage was found. However, correlation
      of the donor T cell repertoire with clinical outcomes of the recipient revealed
      that a higher CD4(+) TCRbeta diversity after G-CSF treatment is associated with
      lower reactivation of cytomegalovirus and Epstein-Barr virus. By contrast, no
      protecting correlation was observed for CD8(+) T cells. In essence, our deep
      TCRbeta analysis identifies the importance of the CD4(+) T cell compartment for
      the control of latent viruses after allogeneic stem cell transplantation. 

PMID- 25873101
TI  - Acupuncture for the treatment of phantom limb pain in lower limb amputees: study
      protocol for a randomized controlled feasibility trial.
AB  - BACKGROUND: Phantom limb pain is a prevalent condition that is difficult to
      manage, with a lack of robust evidence to support the use of many adjunctive
      treatments. Acupuncture can be effective in the management of many painful
      conditions but little is known about its effectiveness in treating phantom limb
      pain. The aim of this study is to explore the feasibility of conducting a
      randomized controlled trial comparing acupuncture and routine care in a group of
      lower limb amputees with phantom limb pain. METHODS/DESIGN: An unstratified,
      pragmatic, randomized, two-armed, controlled trial of parallel design comparing
      acupuncture and usual care control will be conducted. A total of 20 participants
      will be randomly assigned to receive either usual care or usual care plus
      acupuncture. Acupuncture will include eight 1 hour treatments delivered
      pragmatically over 4 weeks by practitioners trained in traditional Chinese
      medicine. As outcome measures, the Numerical Pain Rating Scale, short-form McGill
      Pain Questionnaire 2, EQ-5D-5 L, Hospital Anxiety and Depression Scale, 10-Item
      Perceived Stress Scale, Insomnia Severity Index, and Patient Global Impression of
      Change will be completed at baseline, weekly for the duration of the study and at
      1 month after completion of the study. After completion of the trial,
      participants will provide feedback though semi-structured interviews. Feasibility
      will be determined through the ability to recruit to the study, success of the
      randomization process, completion of acupuncture intervention, acceptability of
      random allocation and completion of outcome measures. Acceptability of the
      acupuncture intervention will be determined through semi-structured interviews
      with participants. The appropriateness of outcome measures for a future trial
      will be addressed through completion rates of questionnaires and participant
      feedback. DISCUSSION: Data generated on effect size will be used for future
      sample size calculations and will inform the development of an appropriate and
      feasible protocol for use in a definitive multicentre randomized controlled
      trial. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02126436.

PMID- 25873103
TI  - Is Patch Testing with Food Additives Useful in Children with Atopic Eczema?
AB  - BACKGROUND: Atopy patch testing is a useful way to determine delayed-type
      hypersensitivity reactions to foods and aeroallergens. Although food additives
      have been accused of worsening atopic eczema symptoms, according to recent
      studies the role of food additives in atopic eczema remains unclear. The purpose
      of our study was to investigate food additive hypersensitivity in a group of
      children with atopic eczema by using standardized atopy patch testing and to
      determine the role of food additive hypersensitivity in atopic eczema. METHODS:
      Thirty-four children with atopic eczema and 33 healthy children were enrolled in
      the study. Children who consumed foods containing additives and did not use
      either antihistamines or local or systemic corticosteroids for at least 7 days
      prior to admission were enrolled in the study. All children were subjected to
      atopy patch testing and after 48 and 72 hours their skin reactions were evaluated
      by using the guidelines. RESULTS: Positive atopy patch test results were
      significantly higher in the atopic eczema group. Forty-one percent of the atopic
      eczema group (n = 14) and 15.2% (n = 5) of the control group had positive atopy
      patch test results with food additives (p = 0.036) (estimated relative risk 1.68,
      case odds 0.7, control odds 0.17). Carmine hypersensitivity and the consumption
      of foods containing carmine, such as gumdrops, salami, and sausage, were
      significantly higher in the children with atopic eczema. CONCLUSION: This is the
      first study investigating hypersensitivity to food additives in children with
      atopic eczema. Our results indicate that carmine may play a role in atopic
      eczema.

PMID- 25873104
TI  - Beneficial effects of Xuebijing injection on random skin flap survival in rats.
AB  - BACKGROUND: Improving survival of random skin flaps has important implications of
      reconstruction, and various kinds of agents have been tested for this purpose. In
      this study, the effects of Xuebijing (XBJ) injection on random skin flap survival
      in rats were evaluated. MATERIALS AND METHODS: McFarlane flaps were established
      in 40 rats divided into two groups. XBJ was injected into the test group, and the
      same concentration of saline was injected into controls. Tissues were stained
      with hematoxylin and eosin stain and immunohistochemically evaluated, and the
      survival area of the flaps, superoxide dismutase, and malondialdehyde contents
      were examined. RESULTS: Compared with the control group, we found the mean
      survival area of the flaps in the test group was significantly larger, expression
      of vascular endothelial growth factor and superoxide dismutase activity increased
      markedly in the test group, malondialdehyde level in the test group was
      significantly lower, and the hematoxylin and eosin-stained slices showed that
      inflammation was clearly inhibited in the test group. CONCLUSIONS: In summary,
      XBJ improved survival of random skin flaps.

PMID- 25873105
TI  - Extreme Flexibility in a Zeolitic Imidazolate Framework: Porous to Dense Phase
      Transition in Desolvated ZIF-4.
AB  - Desolvated zeolitic imidazolate framework ZIF-4(Zn) undergoes a discontinuous
      porous to dense phase transition on cooling through 140 K, with a 23 %
      contraction in unit cell volume. The structure of the non-porous, low temperature
      phase was determined from synchrotron X-ray powder diffraction data and its
      density was found to be slightly less than that of the densest ZIF phase, ZIF
      zni. The mechanism of the phase transition involves a cooperative rotation of
      imidazolate linkers resulting in isotropic framework contraction and pore space
      minimization. DFT calculations established the energy of the new structure
      relative to those of the room temperature phase and ZIF-zni, while DSC
      measurements indicate the entropic stabilization of the porous room temperature
      phase at temperatures above 140 K.

PMID- 25873106
TI  - A reversible and selective chemosensor based on intramolecular NH...NH2 hydrogen
      bonding for cyanide and pH detection.
AB  - A highly selective and reversible chemosensor for cyanide and pH detection was
      developed based on intramolecular NH...NH2 hydrogen bonding.

PMID- 25873107
TI  - CaV3.2 KO mice have altered retinal waves but normal direction selectivity.
AB  - Early in development, before the onset of vision, the retina establishes
      direction-selective responses. During this time period, the retina spontaneously
      generates bursts of action potentials that propagate across its extent. The
      precise spatial and temporal properties of these "retinal waves" have been
      implicated in the formation of retinal projections to the brain. However, their
      role in the development of direction selective circuits within the retina has not
      yet been determined. We addressed this issue by combining multielectrode array
      and cell-attached recordings to examine mice that lack the CaV3.2 subunit of T
      type Ca2+ channels (CaV3.2 KO) because these mice exhibit disrupted waves during
      the period that direction selective circuits are established. We found that the
      spontaneous activity of these mice displays wave-associated bursts of action
      potentials that are altered from that of control mice: the frequency of these
      bursts is significantly decreased and the firing rate within each burst is
      reduced. Moreover, the projection patterns of the retina demonstrate decreased
      eye-specific segregation in the dorsal lateral geniculate nucleus (dLGN).
      However, after eye-opening, the direction selective responses of CaV3.2 KO
      direction selective ganglion cells (DSGCs) are indistinguishable from those of
      wild-type DSGCs. Our data indicate that although the temporal properties of the
      action potential bursts associated with retinal waves are important for activity
      dependent refining of retinal projections to central targets, they are not
      critical for establishing direction selectivity in the retina. 

PMID- 25873108
TI  - Effective targeting of primitive AML CD34+ cells by the second-generation
      proteasome inhibitor carfilzomib.

PMID- 25873110
TI  - [Hormonal therapy in transsexual patients].

PMID- 25873111
TI  - [The most recent aspects of diagnosis and therapy of hyponatraemia].

PMID- 25873112
TI  - [Non-celiac gluten sensitivity].

PMID- 25873113
TI  - [Non-celiac gluten sensitivity].

PMID- 25873114
TI  - [Our experience with hormonal therapy in transsexual patients].
AB  - Hormonal therapy in transsexual patients (TS) includes sexagens administration:
      androgens in female-to-male transsexual patients (FtM) and oestrogens and
      antiandrogens in male-to-female transsexual patients (MtF). Duration of hormonal
      therapy should continue at least 1 year before gender reassignment surgery.
      Hormonal therapy supresses former gender and induces partially new gender
      changes. Hormonal therapy continues subsequently after surgery during life.
      Hormonal therapy in MtF TS includes oestrogens and antiandrogens application. In
      very young persons in both groups blocking gonadoliberin analogues can be used.
      In FtM TS testosterone oneself is given (orally and/or parenterally). Authors
      describe their own experiences with hormonal treatment in 282 TS (163 FtM and 119
      MtF). During hormonal therapy statistically significant weight increasing was
      found in both groups. Total cholesterol increased in FtM. In MtF during hormonal
      therapy average prolactin level increased from 350.1 to 570.5 mU/l without
      clinical significance. Total average hormonal therapy duration was 6.73 years in
      FtM and 4.64 years in MtF and so overall therapy safety assessment is not
      possible. Any endocrinopathy occurence in the beginning of surveillance was found
      in 35 persons (12.4 %): simple goiter, autoimmune thyreoiditis, hypothyroidism,
      hyperthyroidism, gynecomastia, DM type 1, congenital adrenal hyperplasia (CAH),
      Klinefelter syndrome and nonfunctional pituitary adenoma. It is appropriate as
      well as in other rare medicine conditions to manage diagnosing and therapy in
      centers with experience with these issues.

PMID- 25873115
TI  - [Does body height affect the severity of chronic venous disease in lower
      extremities?].
AB  - INTRODUCTION: The effect of obesity on chronic venous disease has been known. The
      effect of body height has not been studied until now, although venous pressure is
      clearly influenced by hydrostatic pressure in the vertical position. METHODS: We
      have examined 1026 lower extremities in 124 men and 392 women with suspected
      chronic venous disease. Their clinical condition was evaluated using CEAP
      classification. Duplex sonography was used to exclude deep venous occlusion and
      to evaluate any present reflux. Venous functions were evaluated based on venous
      pump performance during exercise and according to venous refilling time. RESULTS:
      We confirmed the known, statistically highly significant relationship between age
      and weight, and severity of clinical condition and presence of reflux. We
      provided evidence of significant relationships between the clinical condition and
      plethysmographic parameters. We did not demonstrate a statistically significant
      relationship between body weight and clinical condition, venous refilling time
      after exercise and presence of reflux, and only a weak relationship with respect
      to the performance of venous muscle pump in the right lower extremities.
      CONCLUSION: We did not demonstrate an effect of body height on the severity of
      chronic venous disease.

PMID- 25873116
TI  - [Experiences with biosimilar drugs in therapy].
AB  - Biosimilar drugs or drugs which are similar to reference biological drugs
      represent a new treatment option within the biological treatment. They are
      already the standard biotherapeutics option in some fields of medicine, in others
      as in diabetology, remain to be evaluated. The article presents the definition of
      biosimilar drugs and summarizes the therapeutic benefits and attitudes of
      agencies for drug control in the United States and Europe.

PMID- 25873117
TI  - [The most recent aspects of diagnosis and therapy of hyponatraemia].
AB  - Hyponatraemia is the most common electrolyte disbalance in clinical practice,
      which is associated with increased patients morbidity and mortality. At present
      the pathophysiology of hyponatraemia is explored in more details, antidiuretic
      hormone and osmoregulation play the major roles. This article informs about
      relatively new classification of hyponatraemia for clinical practice based on the
      severity of clinical symptoms and based on the effective serum osmolality. It
      also offers diagnostic and treatment guidelines of hyponatraemia, which are based
      on current recommendations of the world experts and on the evidence based
      medicine.

PMID- 25873118
TI  - [Non-celiac gluten sensitivity].
AB  - Non-celiac gluten sensitivity has recently been recognized by the scientific
      community as a part of gluten-related disorders, and is defined as a condition
      with gastrointestinal and/or extra-intestinal symptoms triggered by gluten
      ingestion in the absence of celiac disease and wheat allergy. Currently, there is
      no specific serological marker and non-celiac gluten sensitivity remains a
      diagnosis of exclusion: testing for celiac disease and wheat allergy must be
      negative, symptoms must improve with a gluten-free diet, and diagnosis must be
      confirmed by the gluten challenge. In this article, we discuss current knowledge
      of pathophysiology, clinical and epidemilogical spectrum, diagnosis, and
      treatment of NCGS. 

PMID- 25873120
TI  - [New ESC guidelines on the diagnosis and management of acute pulmonary embolism].

PMID- 25873119
TI  - [Chronic thromboembolic pulmonary hypertension].
AB  - In recent years, we have witnessed a growing interest in diseases of pulmonary
      circulation. It is due to the development of specific drug therapy for pulmonary
      hypertension (PH), improving the availability and performance of endarterectomy
      techniques of pulmonary artery. This technique has been established as method of
      choice for patients with chronic thromboembolic pulmonary hypertension (CTEPH).
      However, the crucial issue is early indication of treatment, right diagnosis and
      determination of exact type of pulmonary hypertension. Modern therapeutic
      approaches provide better prognosis, quality of life and even possibility to cure
      the patients, especially suffering from CTEPH. This article discusses the issue
      of CTEPH.

PMID- 25873121
TI  - [Pelvic venous congestion syndrome - diagnosis and management. Guidelines of the
      angiology section of slovak medical chamber (2015)].
AB  - Pelvic congestion syndrome: chronic symptoms, which may include pelvic pain,
      perineal heaviness, urgency of micturition, and post-coital pain, caused by
      ovarian and/or pelvic vein reflux and/or obstruction, and which may be associated
      with vulvar, perineal, and/or lower extremity varices. The VEIN-TERM consensus
      document was developed by a transatlantic interdisciplinary faculty of experts
      under the auspices of the American Venous Forum (AVF), the European Venous Forum
      (EVF), the International Union of Phlebology (IUP), the American College of
      Phlebology (ACP), and the International Union of Angiology (IUA). It provides
      recommendations for fundamental venous terminology. Project Vessels of AS SMC.

PMID- 25873122
TI  - [PET-CT documented remission of multicentric Castleman disease after treatment
      with rituximab: case report and review].
AB  - We describe a case of multicentric Castleman disease with generalized
      lymphadenopathy and splenomegaly, accompanied by typical B symptoms - loss of 15
      kg, fever of non-infectious origin, night sweats, symptoms of anemia.
      Histological examination of the nodes with the highest accumulation of
      fluorodeoxyglucose, taken from mediastinum by thoracoscopy, revealed
      plasmocellular type of Castleman disease. Tests for HIV and human herpesvirus 8
      (HHV-8) were negative. Three recurrences of herpes zoster indicating an
      alteration of immunity preceded the dia-gnosis of disease. Treatment was
      initiated with combination of thalidomide, dexamethasone, and cyclophosphamide.
      The response after 2 months therapy was not clear and patient doesn't tolerated
      the therapy well. Therefore, this treatment was terminated and R-CHOP (Mabthera -
      rituximab, cyclophosphamide, adriamycin, vincristine, and prednisone) was
      selected as a second-line therapy. Lymphadenopathy and splenomegaly were reduced
      during the 2 cycles of treatment, however, serious infectious complications
      accompanied the therapy. Therefore, only use of Mabthera monotherapy 375 mg /m2
      was administered in 28-day intervals. This treatment has shown efficacy and
      tolerability. PET-CT scan has demonstrated disappearance of lymphadenopathy and
      splenomegaly, in addition, normalized accumulation of fluorodeoxyglucose.
      Monotherapy with Mabthera has proved to be effective and well tolerated drug in
      this case. Currently, there are more effective therapeutic alternatives in
      multicentric Castleman disease: treatment with monotherapy of rituximab or in
      combination therapy with immunomodulatory drugs (thalidomide or lenalidomide,
      treatment with anti-IL-6 (siltuximab) or against its receptor (tocilizumab). In
      the case of ineffectiveness of one treatment option must be tested other
      alternative. In this case the therapy based on thalidomide wasn't successful,
      whereas the treatment with Mabthera has achieved disappearance of disease
      symptoms.

PMID- 25873123
TI  - [Hypersensitive reaction after application of heparin with activation heparin
      induced trombocytopenia in initiation of intermittent haemodialysis].
AB  - Our report describes the case of patient with hypersensitive reaction regularly
      arising early after initiation of haemodialysis. This characteristic reaction
      with pletoric face coloration, bronchospasm, increase of blood pressure, anxiety
      and decrease of blood oxygen saturation at the consequence and central cyanosis
      was regularly present without dependence on type of dialysis membrane, drug
      premedication or prophylactic flushing haemodialysis system by isotonic natrium
      chloride solution. Low platelet value and trouble-free haemodialysis realized
      without heparin showed real cause of patients problem. Resolution of this state
      was regional citrate anticoagulation during intermitent haemodialysis.

PMID- 25873124
TI  - [Selected legal aspects of compulsory confidentiality].

PMID- 25873125
TI  - [Mild hypoglycaemia is common in type 2 diabetic patients treated with insulin
      analogues in the Czech Republic and the patients are concerned about it: results
      of a GAPP2TM survey (Global Attitudes of Physicians and Patient)].
AB  - OBJECTIVE: Mild hypoglycaemia affects diabetes management, productivity and
      quality of life of patients. Data are scarce about the incidence of mild
      hypoglycaemia in daily life of type 2 diabetic patients treated with insulin
      analogues. The aim was to focus on the incidence of mild hypoglycaemia and its
      consequences in the international GAPP2 survey (Global Attitudes of Patient and
      Physicians) conducted also in the Czech Republic. METHODS: The GAPP2 project -
      Global Attitudes of Patients and Physicians is an international cross-sectional
      study conducted online via Internet in a questionnaire form dedicated to type 2
      diabetic patients treated with insulin analogues and physicians who treat these
      patients. The survey was realized in two steps including 17 countries. The first
      step was completed by six countries in 2012. The second step was terminated by
      additional eleven countries including the Czech Republic in 2014. The survey was
      designed to obtain data on some aspects of insulin therapy and persistent issues
      in daily practice from the views of patients and physicians. One part of survey
      was dedicated to mild hypoglycaemia occurring in treatment with insulin
      analogues. The incidence of mild hypoglycaemia and the reaction of patients and
      physicians on hypoglycaemia (including modification of therapy, self-monitoring)
      were investigated. Moreover, there was investigated the impact of mild
      hypoglycaemia on quality of life from the view of patients and physicians.
      RESULTS: The results of the survey have shown that mild hypoglycaemia is common
      in patients with insulin analogues in the Czech Republic. In addition, patients
      in the Czech Republic are more afraid from hypoglycaemia and feel more limited in
      daily life in comparison to other countries in GAPP2 survey. Patients try to
      avoid nocturnal hypoglycaemia through reduction or omission of prescribed dose of
      insulin. Furthermore, research has observed that physicians are poorly informed
      by patients about incidence and severity of hypoglycaemia. CONCLUSION: The
      incidence of mild hypoglycaemia is in the Czech Republic as common as in other
      countries involved in the GAPP2 survey. However, the Czech patients are more
      afraid and this fact is often hidden before physicians. Increased fear of
      hypoglycaemia suggests inadequate education in terms of how to avoid and manage
      hypoglycaemia. Particular emphasis should be placed on nocturnal hypoglycaemia.
      Physicians should discuss more with patients about issue of hypoglycaemia. It is
      important to motivate patients to share the information with physicians about
      incidence and severity of hypoglycaemia.

PMID- 25873126
TI  - Telmisartan treatment targets inflammatory cytokines to suppress the pathogenesis
      of acute colitis induced by dextran sulphate sodium.
AB  - The renin angiotensin system (RAS) is essential for the regulation of
      cardiovascular and renal functions to maintain the fluid and electrolyte
      homeostasis. Recent studies have demonstrated a locally expressed RAS in various
      tissues of mammals, which is having pathophysiological roles in those organ
      system. Interestingly, local RAS has important role during the inflammatory bowel
      disease pathogenesis. Further to delineate its role and also to identify the
      potential effects of telmisartan, an angiotensin receptor blocker, we have used a
      mouse model of acute colitis induced by dextran sulphate sodium. We have used
      0.01 and 5mg/kg body weight doses of telmisartan and administered as enema to
      facilitate the on-site action and to reduce the systemic adverse effects.
      Telmisartan high dose treatment significantly reduced the disease activity index
      score when compared with the colitis control mice. In addition, oxidative stress
      and endoplasmic reticulum stress markers expression were also significantly
      reduced when compared with the colitis control mice. Subsequent experiments were
      carried out to investigate some of the mechanisms underlying its anti
      inflammatory effects and identified that the mRNA levels of pro-inflammatory
      cytokines such as tumour necrosis factor alpha, interleukin 1beta, interleukin 6
      and monocyte chemoattractant protein 1 as well as cellular DNA damage were
      significantly suppressed when compared with the colitis control mice. Similarly
      the apoptosis marker proteins such as cleaved caspase 3 and 7 levels were down
      regulated and anti-apoptotic protein Bcl2 level was significantly upregulated by
      telmisartan treatment. These results indicate that blockade of RAS by telmisartan
      can be an effective therapeutic option against acute colitis. 

PMID- 25873127
TI  - P2Y12 receptor inhibitors for secondary prevention of ischemic stroke.
AB  - INTRODUCTION: Ischemic stroke (IS) is a major cause of death and disability
      worldwide. The P2Y12 receptor plays a critical role in the formation of a stable
      thrombus leading to ischemic complications. Therefore, P2Y12 receptor inhibitors
      constitute a major antiplatelet strategy in the secondary prevention of IS. AREAS
      COVERED: We searched articles about P2Y12 receptor inhibitors and stroke in
      PubMed published until December 2014. This is a comprehensive review of the role
      of P2Y12 receptor inhibitors alone and in combination with aspirin in the
      secondary prevention of noncardioembolic stroke. EXPERT OPINION: The potential
      benefit of more potent antiplatelet therapy for secondary stroke prevention must
      be weighed against the risk of bleeding in patients with IS. Short-term (<= 3
      months) dual antiplatelet therapy with clopidogrel and aspirin that is initiated
      early after IS or transient ischemic attack due to large artery atherosclerosis
      appears most efficient.

PMID- 25873128
TI  - Direct imaging of the magnetic polarity and reversal mechanism in individual Fe(3
      x)O4 nanoparticles.
AB  - This work reports on the experimental characterization of the magnetic domain
      configurations in cubic, isolated Fe3-xO4 nanoparticles with a lateral size of 25
      30 nm. The magnetic polarity at remanence of single domain ferrimagnetic Fe3-xO4
      nanoparticles deposited onto a carbon-silicon wafer is observed by magnetic force
      microscopy. The orientations of these domains provide a direct observation of the
      magneto-crystalline easy axes in each individual nanoparticle. Furthermore, the
      change in the domain orientation with an external magnetic field gives evidence
      of particle magnetization reversal mediated by a coherent rotation process that
      is also theoretically predicted by micromagnetic calculations. 

PMID- 25873129
TI  - The bilobed flap as a lifeboat flap for a forearm soft tissue defect.

PMID- 25873130
TI  - Theoretical Characterisation of Phosphinyl Radicals and Their Magnetic
      Properties: g Matrix.
AB  - The g matrices (g tensors) of various phosphinyl radicals (R2 P(.) ) were
      calculated using the DFT and multireference configuration interaction (MRCI)
      methods. The g matrices were distinctly dependent on the molecular structure of
      the radical. To thoroughly examine this dependence, the contributions from
      individual atoms and excited states were calculated. The former revealed the gain
      from the phosphorus atom to be preeminent unless P?O or P?S bonds are present in
      the radical molecule. The contributions owing to excited states arising from
      electronic transitions between doubly occupied molecular orbitals and the SOMO
      were clearly positive, as in the case of semiquinone and niroxide radicals. The
      transitions from the phosphorus lone pair were of paramount importance.
      Surprisingly, unlike for semiquinones and nitroxides, a significant negative
      contribution was observed from excitations from the SOMO to unoccupied molecular
      orbitals. For radicals with P?O bonds, this contribution to the g2 component was
      dominant. 

PMID- 25873131
TI  - Treatment strategies for prosthetic valve thrombosis in pregnant patients.

PMID- 25873133
TI  - Neuroprotective effects of brilliant blue G on the brain following traumatic
      brain injury in rats.
AB  - The P2X7 inhibitor, brilliant blue G (BBG), has been reported as a
      neuroprotective drug against a variety of disorders, including neuropathic pain
      and brain ischemia. Currently, no studies have examined the potential for BBG to
      provide neuroprotection in animal models of TBI. The aim of the present study was
      to investigate the neuroprotective effect of BBG on TBI and to determine the
      underlying mechanisms. The rats were subjected to a diffuse cortical impact
      injury caused by a modified weight-drop device, and then divided randomly into
      three groups: the sham-operated, BBG treatment and vehicle groups. In the BBG
      treatment group, 50 mg/kg brilliant blue G (BBG; 100% pure), a highly specific
      and clinically useful P2X7 antagonist, was administered via the tail vein 15 min
      prior to or up to 8 h following TBI. The co-localization of NeuN and protein
      kinase Cgamma (PKCgamma) was followed with immunofluorescent staining. The
      expression of P2X7, PKCgamma and inflammatory cytokines was identified by western
      blot analysis. Wet-dry weight method was used to evaluate brain edema, and motor
      function outcome was examined using the neurological severity score. The present
      study demonstrated that the administration of BBG attenuated TBI-induced cerebral
      edema and the associated motor deficits. Following trauma, BBG treatment
      significantly reduced the levels of PKCgamma and interleukin-1beta in the cortex.
      The results provide in vivo evidence that BBG exerted neuroprotective effects by
      attenuating brain edema and improving neurological functions via reducing
      PKCgamma and interleukin-1beta levels following TBI.

PMID- 25873132
TI  - Aspiration sclerotherapy combined with pasireotide to improve reduction of large
      symptomatic hepatic cysts (SCLEROCYST): study protocol for a randomized
      controlled trial.
AB  - BACKGROUND: Aspiration sclerotherapy is an effective therapeutic option for large
      symptomatic hepatic cysts. However, incomplete cyst reduction following
      aspiration sclerotherapy is frequently reported. Strong post-procedural cyst
      fluid secretion by cholangiocytes, which line the epithelium of the hepatic cyst,
      seems to be associated with lower reduction rates. Previous studies showed that
      somatostatin analogues curtail hepatic cyst fluid production. This trial will
      evaluate the effect of aspiration sclerotherapy combined with the somatostatin
      analogue pasireotide on cyst reduction. By combining treatment modalities we aim
      to improve cyst reduction leading to greater symptomatic relief and reduced rates
      of cyst recurrence. METHODS/DESIGN: This single center, randomized, double-blind,
      placebo-controlled clinical trial evaluates the additional effect of pasireotide
      when combined with aspiration sclerotherapy in patients with a large (>5 cm)
      symptomatic hepatic cyst. A total of 34 participants will be randomized in a 1:1
      ratio. In the active arm, patients will receive pasireotide (long-acting release,
      60 mg injection) two weeks prior to and two weeks following aspiration
      sclerotherapy. Patients in the control arm will receive placebo injections at
      corresponding intervals. The primary outcome is proportional cyst diameter
      reduction four weeks after aspiration sclerotherapy compared to baseline
      measurements, obtained by ultrasonography. As secondary outcomes, proportional
      volume reduction, recurrence, symptomatic relief and improvement of health
      related quality of life will be assessed. Furthermore, safety and tolerability of
      the combination of pasireotide and aspiration sclerotherapy will be evaluated.
      DISCUSSION: This trial aims to improve efficacy of aspiration sclerotherapy by a
      combined approach of two treatment modalities. We hypothesize that pasireotide
      will decrease fluid re-accumulation after aspiration sclerotherapy, leading to
      effective hepatic cyst reduction and symptomatic relief. TRIALS REGISTRATION:
      This trial is registered with ClinicalTrials.gov (identifier: NCT02048319 ;
      registered on 6 January 2014) and EudraCT (identifier: 2013-003168-29; registered
      on 16 August 2013).

PMID- 25873134
TI  - Cis-[RuCl(BzCN)(N-N)(P-P)]PF6 complexes: Synthesis and in vitro antitumor
      activity: (BzCN=benzonitrile; N-N=2,2'-bipyridine; 1,10-phenanthroline; P-P=1,4
      bis(diphenylphosphino) butane, 1,2-bis(diphenylphosphino)ethane, or 1,1'
      (diphenylphosphino)ferrocene).
AB  - The motivation to use ruthenium complexes in cancer treatment has led our
      research group to synthesize complexes with this metal and test them against
      several types of tumor cells, yielding promising results. In this paper the
      results of biological tests, assessed by the MTT (3-(4,5-dimethylthiazol-2-yl)
      2,5-diphenyltetrazolium bromide) assay, were carried out on the complexes cis
      [RuCl(BzCN)(bipy)(dppe)]PF6 (1), cis-[RuCl(BzCN)(bipy)(dppb)]PF6 (2), cis
      [RuCl(BzCN)(bipy)(dppf)]PF6 (3) and cis-[RuCl(BzCN)(phen)(dppb)]PF6 (4) which are
      described [BzCN = b enzonitrile; bipy = 2,2'-bipyridine; phen = 1,10
      phenanthroline; dppe = 1,2-bis(diphenylphosphino) ethane; dppb = 1,4-bis
      (diphenylphosphino)butane; dppf = 1,1'-bis(diphenylphosphino)ferrocene]. The
      present study is focused on the cytotoxic activity of complexes (1)-(4) against
      four tumor cell lines and on the apoptosis and changes in the cell cycle and gene
      expression observed in the sarcoma 180 (S180) tumor cell line treated with
      complex (1). The results demonstrated that this complex inhibits S180 cell
      growth, with an IC50 of 17.02 +/- 8.21 MUM, while exhibiting lower cytotoxicity
      (IC50 = 53.73 +/- 5.71 MUM) towards lymphocytes (normal cells). Flow cytometry
      revealed that the complex inhibits the growth of tumor cells by inducing
      apoptosis as evidenced by an increase in the proportion of cells positive for
      annexin V staining and G0/G1 phase cell-cycle arrest. Further investigation
      showed that complex (1) induces a drop in the mitochondrial membrane potential
      and provokes a decrease in Bcl-2 protein expression and increase in caspase 3
      activation, while the increased activation of caspase 8 caused a decrease in the
      gene expression in caspases 3 and 9. Increases in Tp53 and Bax expressions were
      also observed.

PMID- 25873135
TI  - On Speech Problems with Fixed Restorations on Implants in the Edentulous Maxilla:
      Introduction of a Novel Management Concept.
AB  - BACKGROUND: Little attention has been paid to the effect of implant restorations
      on speech. PURPOSE: The aim of this study was threefold: (1) to find out if
      speech problems occur after inserting a fixed provisional restoration in the
      edentulous maxilla; (2) to explore speech adaptation in case articulation
      problems arise after rehabilitation; and (3) to describe the effect of changing
      the shape of the restoration on improving speech. MATERIALS AND METHODS: Ten
      patients with an edentulous maxilla were treated with fixed rehabilitation on
      implants. Speech evaluation was performed at four occasions: before implant
      surgery, immediately after restoration, and 3 weeks later before and after
      managing the speech problem by changing the shape of the restoration if speech
      problems occurred. Comparative three-dimensional-analysis of casts of the
      restoration before and after changing the shape of the restoration was carried
      out. RESULTS: The majority of patients (n = 7) experienced speech problems
      immediately after rehabilitation. Three weeks later, none of the seven patients
      with deteriorated speech returned to baseline speech. Then, volumetric reduction
      of the palatal aspects of the (pre)molars was performed, which allowed speech to
      return to baseline levels in five out of seven patients. In the two remaining
      patients, the intervention resulted in an improvement of speech without reaching
      their baseline levels. Three-dimensional-analysis showed that reducing the
      palatal volume of the premolars was effective in correcting speech. CONCLUSIONS:
      Speech problems may frequently occur after fixed rehabilitation of the completely
      edentulous maxilla. A novel speech management concept, consisting of reducing the
      palatal volume of the (pre)molars, is introduced, demonstrating to solve speech
      problems in most cases.

PMID- 25873137
TI  - Treatment of depression and anxiety with internet-based cognitive behavior
      therapy in patients with a recent myocardial infarction (U-CARE Heart): study
      protocol for a randomized controlled trial.
AB  - BACKGROUND: Major depression and depressive symptoms are common in patients with
      a recent myocardial infarction (MI), and depression is associated with adverse
      cardiovascular outcomes. Anxiety post-MI is less studied, but occurs commonly in
      patients with heart disease, and is also considered a risk factor for recurrence
      of cardiac events. Cognitive behavior therapy (CBT) is an established therapy for
      depression and anxiety disorders. To the best of our knowledge, there have not
      been any studies to determine if internet-based CBT (iCBT) can reduce the
      symptoms of depression and anxiety in patients with a recent MI. The main aim of
      the U-CARE Heart trial is to evaluate an iCBT intervention for patients with a
      recent MI. METHODS/DESIGN: This is a randomized, controlled, prospective study
      with a multicenter design. A total of 500 participants will be randomized at a
      1:1 ratio, around two months after an acute MI, to either iCBT or to a control
      group. Both groups will receive an optimal standard of care according to
      guidelines. The intervention consists of a self-help program delivered via the
      internet with individual online support from a psychologist. Treatment duration
      is 14 weeks. The primary outcome is change in patients' self-rated anxiety and
      depression symptoms from baseline to end of treatment. An internal pilot study
      was conducted indicating sufficient levels of study acceptability and engagement
      in treatment. DISCUSSION: The present study is designed to evaluate an iCBT
      intervention targeting symptoms of depression and anxiety in a post-MI
      population. If effective, iCBT has several advantages, and will potentially be
      implemented as an easily accessible treatment option added to modern standard of
      care. TRIAL REGISTRATION: This trial was registered with Clinicaltrials.gov
      (identifier: NCT01504191 ) on 19 December 2011.

PMID- 25873138
TI  - Synthesis of molecularly imprinted polypyrrole as an adsorbent for solid-phase
      extraction of warfarin from human plasma and urine.
AB  - The aim of this work was to develop a method for the clean-up and
      preconcentration of warfarin from biological sample employing a new molecularly
      imprinted polymer (MIP) as a selective adsorbent for solid-phase extraction
      (SPE). This MIP was synthesized using warfarin as a template, pyrrole as a
      functional monomer and vinyl triethoxysilane as a cross-linker. The molar ratio
      of 1:4:20 (template-functional monomer-cross-linker) showed the best results.
      Nonimprinted polymers (NIPs) were prepared and treated with the same method, but
      in the absence of warfarin. The prepared polymer was characterized by Fourier
      transmission infrared spectrometry and scanning electron microscopy. An
      adsorption process (SPE) for the removal of warfarin using the fabricated MIPs
      and NIPs was evaluated under various conditions. Effective parameters on warfarin
      extraction, for example, type and volume of elution solvent, pH of sample
      solution, breakthrough volume and maximum loading capacity, were studied. The
      limits of detection were in the range of 0.0035-0.0050 ug mL(-1). Linearity of
      the method was determined in the range of 0.0165-10.0000 ug mL(-1) for plasma and
      0.0115-10.0000 ug mL(-1) for urine with coefficients of determination (R(2))
      ranging from 0.9975 to 0.9985. The recoveries for plasma and urine samples were
      >95%.

PMID- 25873139
TI  - The personal shopper--a pilot randomized trial of grocery store-based dietary
      advice.
AB  - The objective of this study was to test the feasibility and preliminary efficacy
      of a store-based dietary education intervention against traditional clinic-based
      advice. Patients with obesity (n = 55, mean [standard deviation, SD] age
      44.3[9.2] years, 64% women, 87% non-Hispanic Black) were randomized to receive
      dietary counselling either in a grocery store or a clinic. Change between groups
      (analysis of covariance) was assessed for outcomes including: dietary quality
      (Healthy Eating Index--2005 [0-100 points]), and nutritional knowledge (0-65
      point knowledge scale). Both groups reported improved diet quality at the end of
      the study. Grocery participants had greater increases in knowledge (mean [SD]
      change = 5.7 [6.1] points) than clinic participants (mean [SD] change = 3.2 [4.0]
      points) (P = 0.04). Participants enjoyed the store-based sessions. Grocery store
      based visits offer a promising approach for dietary counselling.

PMID- 25873140
TI  - Small Iminocoumarin Derivatives as Red Emitters: From Biological Imaging to
      Highly Photoluminescent Non-doped Micro- and Nanofibres.
AB  - The fluorescence properties of four derivatives of 3-thienyl-2-(N
      dicyanovinyl)iminocoumarin, bearing a diethylamino group in the 7-position or a
      methoxy group in the 6, 7 and 8 positions, were compared in solution and in the
      solid state. The 7-diethylamino derivative was strongly fluorescent in various
      solvents, with marked solvatochromism. Its fluorescence was quenched by
      aggregation. In contrast, the methoxy derivatives were only moderately or weakly
      fluorescent in solution, but two of them were strongly photoluminescent in the
      crystalline state, owing to favourable molecular packing. The 6-methoxy
      derivative even exhibited spectacular crystallization-enhanced emission, examples
      of which are particularly rare for this type of dyes. Dyes were tested for
      biological use. The 7-diethylamino derivative led to particularly strong
      fluorescence staining of the cytoplasm of HCT-116 colon cancer cells. No fading
      was observed over prolonged illumination by the microscope light beam, but a
      phototoxic effect was detected. The use of the dyes as red-emitting materials was
      also investigated. Using easy-to-implement preparation methods, the compounds
      self- assembled to give one-dimensional nano- and microsized particles, including
      millimeter-long microfibres that exhibited clear wave-guiding properties. This
      study shows the value of these low molecular-weight molecules for the preparation
      of new orange and red-emitting fluorescent materials based on totally pure dye. 

PMID- 25873141
TI  - Cell Injury-Induced Release of Fibroblast Growth Factor 2: Relevance to
      Intracerebral Mesenchymal Stromal Cell Transplantations.
AB  - Beneficial effects of intracerebral transplantation of mesenchymal stromal cells
      (MSC) and their derivatives are believed to be mediated mostly by factors
      produced by engrafted cells. However, the mesenchymal cell engraftment rate is
      low, and the majority of grafted cells disappear within a short post
      transplantation period. Here, we hypothesize that dying transplanted cells can
      affect surrounding tissues by releasing their active intracellular components. To
      elucidate the type, amounts, and potency of these putative intracellular factors,
      freeze/thaw extracts of MSC or their derivatives were tested in enzyme-linked
      immunosorbent assays and bioassays. We found that fibroblast growth factor (FGF)2
      and FGF1, but not vascular endothelial growth factor and monocyte chemoattractant
      protein 1 levels were high in extracts despite being low in conditioned media.
      Extracts induced concentration-dependent proliferation of rat cortical neural
      progenitor cells and human umbilical vein endothelial cells; these proliferative
      responses were specifically blocked by FGF2-neutralizing antibody. In the
      neuropoiesis assay with rat cortical cells, both MSC extracts and killed cells
      induced expression of nestin, but not astrocyte differentiation. However,
      suspensions of killed cells strongly potentiated the astrogenic effects of live
      MSC. In transplantation-relevant MSC injury models (peripheral blood cell
      mediated cytotoxicity and high cell density plating), MSC death coincided with
      the release of intracellular FGF2. The data showed that MSC contain a major depot
      of active FGF2 that is released upon cell injury and is capable of acutely
      stimulating neuropoiesis and angiogenesis. We therefore propose that both dying
      and surviving grafted MSC contribute to tissue regeneration. 

PMID- 25873143
TI  - Off-pump Skeletonized Versus Pedicled Left Internal Mammary Artery Grafting: Mid
      term Results.
AB  - BACKGROUND: Skeletonization of the internal mammary artery for single left
      internal mammary artery (LIMA) use remains controversial. We sought to elucidate
      the effect of different harvesting techniques applied in single LIMA grafting.
      METHOD: Between January 2006 and January 2012, 982 patients undergoing off-pump
      coronary artery bypass with pedicled LIMA conduits (P Group) and 928 patients
      undergoing the same operation with skeletonized LIMA conduits (S Group) were
      enrolled. The length and blood flow of the conduits, and in-hospital and mid-term
      outcomes with one-year postoperative graft angiographic results were analyzed and
      compared between groups. RESULTS: Twenty-five (2.7%) patients in the S group died
      in hospital, compared with 26 (2.6%) in the P group, with similar rates of
      sternal wound infection, chest wall pain, and low-output syndrome. Although the
      length and blood flow of conduits were increased in the S Group, postoperative
      conduit patency was similar between groups (p = 0.470). During a median follow-up
      of 32.2 months, the groups showed similar total survival (88.3 +/- 3.2%, S Group;
      85.5 +/- 2.0%, P Group; p = 0.118) and cardiac event-free survival (82.7 +/-
      3.3%, S Group; 80.3 +/- 2.0%; P Group; p = 0.129), with similar postoperative
      complications. CONCLUSIONS: Skeletonization of single LIMA has no extra benefit
      in early or mid-term outcomes, suggesting no advantage over the pedicled
      technique.

PMID- 25873142
TI  - Advancing Survivors' Knowledge (ASK) about skin cancer study: study protocol for
      a randomized controlled trial.
AB  - BACKGROUND: Advances in treatment have increased childhood cancer 5-year survival
      rates to greater than 80%. However, children previously treated with radiation
      are at significantly increased risk of developing subsequent neoplasms, the most
      common of which are skin cancers. The National Cancer Institute and Children's
      Oncology Group have issued recommendations for survivors treated with radiation
      to perform monthly skin self-examinations and receive a physician skin
      examination at least annually, as early detection has demonstrated markedly
      improved outcomes in the diagnosis and treatment of skin cancers. The goal of the
      present study is to increase rates of skin self-examinations and clinical skin
      examinations among adult survivors of childhood cancer treated with radiation.
      METHODS/DESIGN: This randomized controlled trial uses a 3-group comparative
      effectiveness design comparing: (1) Patient Activation and Education (PAE)
      including text messaging, print and web-based tutorials over 12 months; (2) PAE
      plus physician activation (PAE + MD) adding physician activation/educational
      materials about survivors' increased skin cancer risk and conducting full-body
      skin exams; and (3) PAE plus physician activation, plus teledermoscopy (PAE + MD
      + TD) adding participant receipt of a dermatoscope intended to empower them to
      photograph suspect moles or lesions for review by the study dermatologist.
      DISCUSSION: The current study addresses barriers to screening in this population
      by providing educational and motivational information for both survivors and
      physicians regarding the value of periodic skin examinations. It also utilizes
      innovative mobile health technology to encourage and motivate (that is activate)
      survivors to conduct skin self-examinations, request physician exams, and obtain
      treatment when worrisome lesions are found. Finally, as a comparative
      effectiveness trial, this study isolates the effects of adding specific
      components to the patient activation intervention to test the most effective
      intervention for enhancing skin examination vigilance among this high-risk group.
      TRIAL REGISTRATION: Clinicaltrials.gov: NCT02046811 ; Registration date: 22
      January 2014.

PMID- 25873145
TI  - On the consequences of ignoring purging on genetic recommendations for minimum
      viable population rules.

PMID- 25873144
TI  - Study protocol for a randomised controlled trial of insulin delivery by
      continuous subcutaneous infusion compared to multiple daily injections.
AB  - BACKGROUND: Intensive insulin therapy with continuous subcutaneous insulin
      infusion (CSII) devices or multiple daily injections (MDI) reduces the risk of
      long-term vascular complications of type I diabetes (TID). Both treatments are
      used routinely, but there is little evidence to demonstrate superiority of either
      treatment. If CSII treatment reduces the risk of long-term complications or is
      associated with an improved quality of life (QoL), the additional cost of this
      therapy may be compensated for by a reduction in long-term health expenditure. If
      there is no demonstrable difference between treatments, health-care resources may
      be better invested elsewhere. This study aims to address this gap in knowledge.
      METHODS/DESIGN: This is a pragmatic, randomised controlled trial (RCT). Fifteen
      centres, selected to represent a population with a broad demographic, will
      recruit 316 patients, newly diagnosed with TID, aged between 7 months and 15
      years. Exclusion criteria include additional pathologies or treatments likely to
      affect glycaemic control and a first-degree relative with TID. Randomisation to
      CSII or MDI is stratified for age, gender and recruiting centre. The randomised
      treatment starts within 15 days of diagnosis. Patients will be trained to adjust
      their insulin dose according to carbohydrate intake and blood glucose level.
      Study visits coincide with routine clinic appointments at 3, 6, 9 and 12 months
      when data relating to routine clinical assessments, adverse events and
      concomitant medications are collected. Health utilities questionnaires are
      completed at each visit and a diabetes-specific QoL questionnaire (PedsQL) at
      diagnosis, 6 and 12 months. The primary outcome is glycaemic control (HbA1c) at
      12 months. Secondary outcome measures include QoL, insulin use, growth and weight
      gain, adverse events and a health economics appraisal. DISCUSSION: This is the
      first adequately powered RCT comparing CSII and MDI in a non-selected population,
      treated according to standard practice guidelines. It will produce data that are
      meaningful to individual patients and local and national policymakers. TRIAL
      REGISTRATION: The study was registered with the European Clinical Trials Database
      on 4 November 2010, reference 2010-023792-25.

PMID- 25873146
TI  - High Y-chromosomal diversity and low relatedness between paternal lineages on a
      communal scale in the Western European Low Countries during the surname
      establishment.
AB  - There is limited knowledge on the biological relatedness between citizens and on
      the demographical dynamics within villages, towns and cities in pre-17th century
      Western Europe. By combining Y-chromosomal genotypes, in-depth genealogies and
      surname data in a strict genetic genealogical approach, it is possible to provide
      insights into the genetic diversity and the relatedness between indigenous
      paternal lineages within a particular community at the time of the surname
      adoption. To obtain these insights, six Flemish communities were selected in this
      study based on the differences in geography and historical development. After
      rigorous selection of appropriate DNA donors, low relatedness between Y
      chromosomes of different surnames was found within each community, although there
      is co-occurrence of these surnames in each community since the start of the
      surname adoption between the 14th and 15th century. Next, the high communal
      diversity in Y-chromosomal lineages was comparable with the regional diversity
      across Flanders at that time. Moreover, clinal distributions of particular Y
      chromosomal lineages between the communities were observed according to the
      clinal distributions earlier observed across the Flemish regions and Western
      Europe. No significant indication for genetic differences between communities
      with distinct historical development was found in the analysis. These genetic
      results provide relevant information for studies in historical sciences,
      archaeology, forensic genetics and genealogy. 

PMID- 25873147
TI  - Joint prediction of multiple quantitative traits using a Bayesian multivariate
      antedependence model.
AB  - Predicting organismal phenotypes from genotype data is important for preventive
      and personalized medicine as well as plant and animal breeding. Although genome
      wide association studies (GWAS) for complex traits have discovered a large number
      of trait- and disease-associated variants, phenotype prediction based on
      associated variants is usually in low accuracy even for a high-heritability trait
      because these variants can typically account for a limited fraction of total
      genetic variance. In comparison with GWAS, the whole-genome prediction (WGP)
      methods can increase prediction accuracy by making use of a huge number of
      variants simultaneously. Among various statistical methods for WGP, multiple
      trait model and antedependence model show their respective advantages. To take
      advantage of both strategies within a unified framework, we proposed a novel
      multivariate antedependence-based method for joint prediction of multiple
      quantitative traits using a Bayesian algorithm via modeling a linear relationship
      of effect vector between each pair of adjacent markers. Through both simulation
      and real-data analyses, our studies demonstrated that the proposed antedependence
      based multiple-trait WGP method is more accurate and robust than corresponding
      traditional counterparts (Bayes A and multi-trait Bayes A) under various
      scenarios. Our method can be readily extended to deal with missing phenotypes and
      resequence data with rare variants, offering a feasible way to jointly predict
      phenotypes for multiple complex traits in human genetic epidemiology as well as
      plant and livestock breeding. 

PMID- 25873148
TI  - Contrasting patterns of clonality and fine-scale genetic structure in two rare
      sedges with differing geographic distributions.
AB  - For plants with mixed reproductive capabilities, asexual reproduction is more
      frequent in rare species and is considered a strategy for persistence when sexual
      recruitment is limited. We investigate whether asexual reproduction contributes
      to the persistence of two co-occurring, rare sedges that both experience
      irregular seed set and if their differing geographic distributions have a role in
      the relative contribution of clonality. Genotypic richness was high (R=0.889+/
      0.02) across the clustered populations of Lepidosperma sp. Mt Caudan and, where
      detected, clonal patches were small, both in ramet numbers (?3 ramets/genet) and
      physical size (1.3+/-0.1 m). In contrast, genotypic richness was lower in the
      isolated L. sp. Parker Range populations, albeit more variable (R=0.437+/-0.13),
      with genets as large as 17 ramets and up to 5.8 m in size. Aggregated clonal
      growth generated significant fine-scale genetic structure in both species but to
      a greater spatial extent and with additional genet-level structure in L. sp.
      Parker Range that is likely due to restricted seed dispersal. Despite both
      species being rare, asexual reproduction clearly has a more important role in the
      persistence of L. sp. Parker Range than L. sp. Mt Caudan. This is consistent with
      our prediction that limitations to sexual reproduction, via geographic isolation
      to effective gene exchange, can lead to greater contributions of asexual
      reproduction. These results demonstrate the role of population isolation in
      affecting the balance of alternate reproductive modes and the contextual nature
      of asexual reproduction in rare species. 

PMID- 25873149
TI  - High-density linkage mapping aided by transcriptomics documents ZW sex
      determination system in the Chinese mitten crab Eriocheir sinensis.
AB  - The sex determination system in crabs is believed to be XY-XX from karyotypy, but
      centromeres could not be identified in some chromosomes and their morphology is
      not completely clear. Using quantitative trait locus mapping of the gender
      phenotype, we revealed a ZW-ZZ sex determination system in Eriocheir sinensis and
      presented a high-density linkage map covering ~98.5% of the genome, with 73
      linkage groups corresponding to the haploid chromosome number. All sex-linked
      markers in the family we used were located on a single linkage group, LG60, and
      sex linkage was confirmed by genome-wide association studies (GWAS). Forty-six
      markers detected by GWAS were heterozygous and segregated only in the female
      parent. The female LG60 was thus the putative W chromosome, with the homologous
      male LG60 as the Z chromosome. The putative Z and W sex chromosomes were
      identical in size and carried many homologous loci. Sex ratio (5:1) skewing
      towards females in induced triploids using unrelated animals also supported a ZW
      ZZ system. Transcriptome data were used to search for candidate sex-determining
      loci, but only one LG60 gene was identified as an ankyrin-2 gene. Double sex- and
      mab3-related transcription factor 1 (Dmrt1), a Z-linked gene in birds, was
      located on a putative autosome. With complete genome sequencing and
      transcriptomic data, more genes on putative sex chromosomes will be
      characterised, thus leading towards a comprehensive understanding of the sex
      determination and differentiation mechanisms of E. sinensis, and decapod
      crustaceans in general. 

PMID- 25873150
TI  - Contemporary and historic factors influence differently genetic differentiation
      and diversity in a tropical palm.
AB  - Population genetics theory predicts loss in genetic variability because of drift
      and inbreeding in isolated plant populations; however, it has been argued that
      long-distance pollination and seed dispersal may be able to maintain gene flow,
      even in highly fragmented landscapes. We tested how historical effective
      population size, historical migration and contemporary landscape structure, such
      as forest cover, patch isolation and matrix resistance, affect genetic
      variability and differentiation of seedlings in a tropical palm (Euterpe edulis)
      in a human-modified rainforest. We sampled 16 sites within five landscapes in the
      Brazilian Atlantic forest and assessed genetic variability and differentiation
      using eight microsatellite loci. Using a model selection approach, none of the
      covariates explained the variation observed in inbreeding coefficients among
      populations. The variation in genetic diversity among sites was best explained by
      historical effective population size. Allelic richness was best explained by
      historical effective population size and matrix resistance, whereas genetic
      differentiation was explained by matrix resistance. Coalescence analysis revealed
      high historical migration between sites within landscapes and constant historical
      population sizes, showing that the genetic differentiation is most likely due to
      recent changes caused by habitat loss and fragmentation. Overall, recent
      landscape changes have a greater influence on among-population genetic variation
      than historical gene flow process. As immediate restoration actions in landscapes
      with low forest amount, the development of more permeable matrices to allow the
      movement of pollinators and seed dispersers may be an effective strategy to
      maintain microevolutionary processes. 

PMID- 25873151
TI  - Effect of cycle ergometer and conventional exercises on rehabilitation of older
      patients with total hip arthroplasty: study protocol for randomized controlled
      trial.
AB  - BACKGROUND: Total hip arthroplasty (THA) is an increasingly common treatment for
      older patients with hip osteoarthritis. The best strategy for a physiotherapy
      intervention for older people after THA is not clear in the literature. The
      purpose of this protocol study is to test the feasibility of undertaking a full
      trial clinical to evaluate the effect of ergometer cycling-associated
      conventional exercises on functional results and health-related quality of life
      (HRQOL) of older patients with THA. METHODS/DESIGN: This study protocol is a
      prospective, single center, randomized controlled pilot clinical trial. Older
      patients (>=60 years) in the postoperative phase after primary unilateral THA for
      hip osteoarthritis will be consecutively recruited for this study and randomly
      allocated to 2 treatment groups. Group I will perform cycle ergometer and
      conventional exercises, and group II will perform only conventional exercises.
      The sessions will be conducted twice a week for 8 weeks. Assessments will be made
      at baseline (2 weeks postoperatively: the moment that the patients receive a
      referral for physical therapy, which will start after suture removal), after
      intervention (10 weeks postoperatively), and at 6 months of follow-up (24 weeks
      postoperatively). The primary outcomes are the function, evaluated using the
      Harris Hip Score (HHS) and the Short Physical Performance Battery (SPPB). The
      secondary outcome is HRQOL, measured using 2 evaluation instruments: the Medical
      Outcomes Study 36-Item Short-Form Health Survey (SF-36) and the Western Ontario
      and McMaster Universities Osteoarthritis Index (WOMAC). Data collectors will be
      blinded and will not have contact with participants during the interventions.
      DISCUSSION: This randomized controlled trial will provide evidence regarding the
      effect of this exercise therapy on physical function and quality of life in older
      patients after THA. If our hypothesis is correct, both interventions will be
      effective, but the exercises on the cycle ergometer conferring better results in
      function, physical performance and quality of life. The study follows
      Consolidated Standards of Reporting Trials (CONSORT) guidelines, and the approval
      of the local ethics committee has been obtained. TRIAL REGISTRATION:
      ClinicalTrials.gov: NCT01622465 (14 June 2012).

PMID- 25873152
TI  - Short-stretch inelastic compression bandage in knee swelling following total knee
      arthroplasty study (STICKS): study protocol for a randomised controlled
      feasibility study.
AB  - BACKGROUND: Enhanced recovery programmes in total knee arthroplasty are well
      established. Post-operative knee swelling is common and impairs early post
      operative function. The use of a short-stretch, inelastic compression bandage is
      hypothesised to reduce knee swelling and improve pain and early function. A study
      was designed to test feasibility with a view to informing a larger, future trial
      and to provide preliminary data. METHODS/DESIGN: This is a randomised controlled
      feasibility study. Fifty consecutive patients selected for primary total knee
      arthroplasty will be enrolled in the trial. Patients with a BMI >35, latex
      allergy or neurological or peripheral vascular disease are excluded. Patients are
      randomised by distance randomisation to receive a compression bandage for 24
      hours after surgery or a standard wool and crepe bandage. The bandages are
      applied by one of two consultant surgeons who have had training with their
      application. Knee swelling, range of motion and pain scores will be compared pre
      operatively and at day 1, day 2 and at 6 weeks between groups. The Oxford knee
      score and EQ-5D health status will be compared pre-operatively and at 6 months
      between groups. Recruitment rates, retention rates, resource allocation,
      completeness of data collection, and tolerance and complications with the
      compression bandage are recorded. Descriptive statistics are used to calculate a
      standard deviation for post-operative knee swelling in the groups and to perform
      a power calculation incorporating anticipated patient retention rates to inform a
      future trial. Preliminary data will be analysed using the independent samples t
      test for equal distributions and the Mann-Whitney U for unequal distributions
      with the significance denoted at P <0.05. DISCUSSION: Enhanced recovery
      programmes have revolutionized the management of total knee arthroplasty. There
      is a paucity of clinical data regarding the efficacy of compression bandages.
      Large, randomised controlled trials are uncommon in orthopaedic surgery. The
      results of this study will provide feasibility and preliminary data prior to the
      construction of a larger, multicentre study. TRIAL REGISTRATION: The study was
      registered with Current Controlled Trials ( ISRCTN86903140 ) on 30 May 2013.

PMID- 25873153
TI  - All-photonic quantum repeaters.
AB  - Quantum communication holds promise for unconditionally secure transmission of
      secret messages and faithful transfer of unknown quantum states. Photons appear
      to be the medium of choice for quantum communication. Owing to photon losses,
      robust quantum communication over long lossy channels requires quantum repeaters.
      It is widely believed that a necessary and highly demanding requirement for
      quantum repeaters is the existence of matter quantum memories. Here we show that
      such a requirement is, in fact, unnecessary by introducing the concept of all
      photonic quantum repeaters based on flying qubits. In particular, we present a
      protocol based on photonic cluster-state machine guns and a loss-tolerant
      measurement equipped with local high-speed active feedforwards. We show that,
      with such all-photonic quantum repeaters, the communication efficiency scales
      polynomially with the channel distance. Our result paves a new route towards
      quantum repeaters with efficient single-photon sources rather than matter quantum
      memories. 

PMID- 25873154
TI  - Proteomic profiling of 16 cereal grains and the application of targeted
      proteomics to detect wheat contamination.
AB  - Global proteomic analysis utilizing SDS-PAGE, Western blotting and LC-MS/MS of
      total protein and gluten-enriched extracts derived from 16 economically important
      cereals was undertaken, providing a foundation for the development of MS-based
      quantitative methodologies that would enable the detection of wheat contamination
      in foods. The number of proteins identified in each grain correlated with the
      number of entries in publicly available databases, highlighting the importance of
      continued advances in genome sequencing to facilitate accurate protein
      identification. Subsequently, candidate wheat-specific peptide markers were
      evaluated by multiple-reaction monitoring MS. The selected markers were unique to
      wheat, yet present in a wide range of wheat varieties that represent up to 80% of
      the bread wheat genome. The final analytical method was rapid (15 min) and robust
      (CV < 10%), showed linearity (R(2) > 0.98) spanning over 3 orders of magnitude,
      and was highly selective and sensitive with detection down to 15 mg/kg in
      intentionally contaminated soy flour. Furthermore, application of this technology
      revealed wheat contamination in commercially sourced flours, including rye,
      millet, oats, sorghum, buckwheat and three varieties of soy. 

PMID- 25873155
TI  - Mixed methods feasibility study for a trial of blood pressure telemonitoring for
      people who have had stroke/transient ischaemic attack (TIA).
AB  - BACKGROUND: Good blood pressure (BP) control reduces the risk of recurrence of
      stroke/transient ischaemic attack (TIA). Although there is strong evidence that
      BP telemonitoring helps achieve good control, none of the major trials have
      considered the effectiveness in stroke/TIA survivors. We therefore conducted a
      feasibility study for a trial of BP telemonitoring for stroke/TIA survivors with
      uncontrolled BP in primary care. METHOD: Phase 1 was a pilot trial involving 55
      patients stratified by stroke/TIA randomised 3:1 to BP telemonitoring for 6
      months or usual care. Phase 2 was a qualitative evaluation and comprised semi
      structured interviews with 16 trial participants who received telemonitoring and
      3 focus groups with 23 members of stroke support groups and 7 carers. RESULTS:
      Overall, 125 patients (60 stroke patients, 65 TIA patients) were approached and
      55 (44%) patients were randomised including 27 stroke patients and 28 TIA
      patients. Fifty-two participants (95%) attended the 6-month follow-up
      appointment, but one declined the second daytime ambulatory blood pressure
      monitoring (ABPM) measurement resulting in a 93% completion rate for ABPM - the
      proposed primary outcome measure for a full trial. Adherence to telemonitoring
      was good; of the 40 participants who were telemonitoring, 38 continued to provide
      readings throughout the 6 months. There was a mean reduction of 10.1 mmHg in
      systolic ABPM in the telemonitoring group compared with 3.8 mmHg in the control
      group, which suggested the potential for a substantial effect from
      telemonitoring. Our qualitative analysis found that many stroke patients were
      concerned about their BP and telemonitoring increased their engagement, was easy,
      convenient and reassuring. CONCLUSIONS: A full-scale trial is feasible, likely to
      recruit well and have good rates of compliance and follow-up. TRIAL REGISTRATION:
      ISRCTN61528726 15/12/2011.

PMID- 25873157
TI  - The Soret absorption band of isolated chlorophyll a and b tagged with quaternary
      ammonium ions.
AB  - We have performed gas-phase absorption spectroscopy in the Soret-band region of
      chlorophyll (Chl) a and b tagged by quaternary ammonium ions together with time
      dependent density functional theory (TD-DFT) calculations. This band is the
      strongest in the visible region of metalloporphyrins and an important reporter on
      the microenvironment. The cationic charge tags were tetramethylammonium,
      tetrabutylammonium, and acetylcholine, and the dominant dissociation channel in
      all cases was breakage of the complex to give neutral Chl and the charge tag as
      determined by photoinduced dissociation mass spectroscopy. Two photons were
      required to induce fragmentation on the time scale of the experiment
      (microseconds). Action spectra were recorded where the yield of the tag as a
      function of excitation wavelength was sampled. These spectra are taken to
      represent the corresponding absorption spectra. In the case of Chl a we find that
      the tag hardly influences the band maximum which for all three tags is at 403 +/-
      5 nm. A smaller band with maximum at 365 +/- 10 nm was also measured for all
      three complexes. The spectral quality is worse in the case of Chl b due to lower
      ion beam currents; however, there is clear evidence for the absorption being to
      the red of that of Chl a (most intense peak at 409 +/- 5 nm) and also a more
      split band. Our results demonstrate that the change in the Soret-band spectrum
      when one peripheral substituent (CH3) is replaced by another (CHO) is an
      intrinsic effect. First principles TD-DFT calculations agree with our
      experiments, supporting the intrinsic nature of the difference between Chl a and
      b and also displaying minimal spectral changes when different charge tags are
      employed. The deviations between theory and experiment have allowed us to
      estimate that the Soret-band absorption maxima in vacuo for the neutral Chl a and
      Chl b should occur at 405 nm and 413 nm, respectively. Importantly, the Soret
      bands of the isolated species are significantly blueshifted compared to those of
      solvated Chl and Chl-proteins. The protein microenvironment is certainly not
      innocent of perturbing the electronic structure of Chls. 

PMID- 25873156
TI  - Copy number variants and genetic polymorphisms in TBX21, GATA3, Rorc, Foxp3 and
      susceptibility to Behcet's disease and Vogt-Koyanagi-Harada syndrome.
AB  - This study aimed to investigate the role of genetic variants including single
      nucleotide polymorphisms (SNPs) and copy number variants (CNVs) of TBX21, GATA3,
      Rorc and Foxp3 genes in Behcet's disease (BD) and Vogt-Koyanagi-Harada (VKH)
      syndrome in a Chinese Han population. Genotyping of 25 SNPs was performed by
      iPLEX system (Sequenom) or polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP). TaqMan real time PCR was used to assess CNVs. The
      expression of Rorc and Foxp3 were examined by real-time PCR and cytokine
      production was measured by ELISA. High Rorc CNV was associated with the
      susceptibility to BD (P = 8.99 * 10(-8), OR = 3.0), and low Foxp3 CNV predisposed
      to BD in female patients (P = 1.92 * 10(-5), OR = 3.1). CNVs for the investigated
      genes were not altered in VKH syndrome. Further functional studies demonstrated
      that the relative mRNA expression levels of Rorc were increased in individuals
      with high Rorc copy number, but not for Foxp3. Increased production of IL-1beta
      and IL-6 was found in individuals carrying a high CNV of Rorc. Our study showed
      that high CNVs of Rorc and low CNVs of Foxp3 confer risk for BD but not for VKH
      syndrome. The tested 25 SNPs in TBX21, GATA3, Rorc and Foxp3 did not associate
      with BD and VKH syndrome. 

PMID- 25873158
TI  - Nano-LED array fabrication suitable for future single photon lithography.
AB  - We report on an alternative illumination concept for a future lithography based
      on single-photon emitters and important technological steps towards its
      implementation. Nano light-emitting diodes (LEDs) are chosen as the photon
      emitters. First, the development of their fabrication and their integration
      technology is presented, then their optical characteristics assessed. Last, size
      controlled nano-LEDs, well positioned in an array, are electrically driven and
      utilized for illumination. Nanostructures are lithographically formed,
      demonstrating the feasibility of the approach. The potential of single-photon
      lithography to reach the ultimate scale limits in mass production is discussed. 

PMID- 25873159
TI  - E. coli OxyS non-coding RNA does not trigger RNAi in C. elegans.
AB  - The discovery of RNA interference (RNAi) in C. elegans has had a major impact on
      scientific research, led to the rapid development of RNAi tools and has inspired
      RNA-based therapeutics. Astonishingly, nematodes, planaria and many insects take
      up double-stranded RNA (dsRNA) from their environment to elicit RNAi; the
      biological function of this mechanism is unclear. Recently, the E. coli OxyS non
      coding RNA was shown to regulate gene expression in C. elegans when E. coli is
      offered as food. This was surprising given that C. elegans is unlikely to
      encounter E. coli in nature. To directly test the hypothesis that the E. coli
      OxyS non-coding RNA triggers the C. elegans RNAi pathway, we sequenced small RNAs
      from C. elegans after feeding with bacteria. We clearly demonstrate that the OxyS
      non-coding RNA does not trigger an RNAi response in C. elegans. We conclude that
      the biology of environmental RNAi remains to be discovered. 

PMID- 25873160
TI  - Hydrogen sulfide attenuates cytokine production through the modulation of
      chromatin remodeling.
AB  - Hydrogen sulfide (H2S) is an endogenous gaseous biological mediator, which
      regulates, among others, the oxidative balance of cells under normal
      physiological conditions, as well as in various diseases. Several previous
      studies have reported that H2S attenuates inflammatory mediator production. In
      this study, we investigated the role of H2S in chromatin modulation in an in
      vitro model of lipopolysaccharide (LPS)-induced inflammation and evaluated its
      effects on inflammatory cytokine production. Tamm-Horsfall protein 1 (THP-1)
      differentiated macrophages were pre-treated with sodium hydrosulfide (NaHS) (an
      H2S donor) at 0.01, 0.1, 0.5 or 1 mM for 30 min. To stimulate cytokine
      production, the cells were challenged with bacterial LPS (1 ug/ml) for 1, 4, 8 or
      24 h. Histone H3 acetylation was analyzed by chromatin immunoprecipitation
      (ChIP), cytokine production was measured by ELISA and histone deacetylase (HDAC)
      activity was analyzed using a standard biochemical assay. H2S inhibited the
      production of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in
      a concentration-dependent manner; it was most effective at the two highest
      concentrations used. This effect was associated with a decrease in histone H3
      acetylation at the IL-6 and TNF-alpha promoters in the cells exposed to H2S or
      H2S + LPS. The findings of the present study suggest that H2S suppresses histone
      acetylation, which, in turn, inhibits chromatin openness, leading to a decrease
      in the gene transcription of various pro-inflammatory cytokines. Therefore, this
      mechanism may contribute to the previously demonstrated anti-inflammatory effects
      of H2S and various H2S donors.

PMID- 25873161
TI  - Learning curve for laparoscopic major hepatectomy.
AB  - BACKGROUND: Laparoscopic major hepatectomy (LMH) is evolving as an important
      surgical approach in hepatopancreatobiliary surgery. The present study aimed to
      evaluate the learning curve for LMH at a single centre. METHODS: Data for all
      patients undergoing LMH between January 1998 and September 2013 were recorded in
      a prospective database and analysed. The learning curve for operating time (OT)
      was evaluated using the cumulative sum (CUSUM) method. RESULTS: Of 173 patients
      undergoing major hepatectomy, left hepatectomy was performed in 28 (16.2 per
      cent), left trisectionectomy in nine (5.2 per cent), right hepatectomy in 115
      (66.5 per cent), right trisectionectomy in 13 (7.5 per cent) and central
      hepatectomy in eight (4.6 per cent). Median duration of surgery was 270 (range
      100-540) min and median blood loss was 300 (10-4500) ml. There were 20
      conversions to an open procedure (11.6 per cent). Vascular clamping was
      independently associated with conversion on multivariable analysis (hazard ratio
      5.95, 95 per cent c.i. 1.24 to 28.56; P = 0.026). The CUSUMOT learning curve was
      modelled as a parabola (CUSUMOT  = 0.2149 * patient number(2)  - 30.586 * patient
      number - 1118.3; R(2)  = 0.7356). The learning curve comprised three phases:
      phase 1 (45 initial patients), phase 2 (30 intermediate patients) and phase 3
      (the subsequent 98 patients). Although right hepatectomy was most common in phase
      1, a significant decrease was observed from phase 1 to 3 (P = 0.007) in favour of
      more complex procedures. CONCLUSION: The learning curve for LMH consisted of
      three characteristic phases identified by CUSUM analysis. The data suggest that
      the learning phase of LMH included 45 to 75 patients.

PMID- 25873162
TI  - Errors upstream and downstream to the Universal Protocol associated with wrong
      surgery events in the Veterans Health Administration.
AB  - BACKGROUND: The Universal Protocol has been associated with the prevention of
      wrong surgery procedures; however, such events still occur. This article explores
      wrong surgery events, defined as those incorrect procedures (wrong site, wrong
      side, wrong procedure, wrong patient, wrong level, wrong implant) that would have
      occurred despite the Universal Protocol including the performance of a time-out
      by the surgical team. Understanding why some of these events are not caught by
      the steps of the Universal Protocol, culminating in the time-out, can help the
      field to add upstream and downstream safeguards to help prevent these never
      events. METHODS: The Veterans Health Administration database of root cause
      analyses was queried for all cases involving an incorrect surgical procedure
      between 2004 and 2013 to determine the relative frequency and characteristics of
      wrong surgery events because of errors upstream and downstream to the Universal
      Protocol. This subgroup of wrong surgery events was selected from among all the
      wrong surgery events by 2 clinicians with expertise in patient safety (Kappa =
      .91). RESULTS: Forty-eight cases of wrong surgery events because of
      upstream/downstream errors were analyzed, representing 16% of the 308 root cause
      analyses for wrong surgery events reported during this period. Upstream errors
      included mislabeling of specimens, while downstream errors were associated with
      ineffective intraoperative process. Surgical procedures that were particularly
      vulnerable included wrong level spine operations, wrong patient prostatectomies,
      wrong implant cataract procedures, and wrong site skin lesion excisions.
      CONCLUSIONS: Wrong surgery events can and do occur despite adherence to Universal
      Protocol including a time-out. The prevention of incorrect procedures requires
      complementary safety behaviors and technologies to address errors that occur
      upstream and downstream to the Universal Protocol and the time-out.

PMID- 25873163
TI  - Phyllodes tumors in African American women.
AB  - BACKGROUND: Phyllodes is a rare tumor accounting for less than 1% of all breast
      neoplasms. Studies defining clinical predictors of malignant phyllodes (MP) are
      rare and inconsistent. Furthermore, MP occurrence in African American (AA) women
      has never been analyzed. This study will delineate clinical and pathologic
      features in AA patients that may reasonably predict the probability of
      malignancy. METHODS: A retrospective study of clinical records was carried out
      for 50 AA patients diagnosed with phyllodes tumors (PT) and treated between 1982
      and 2012. Patients' charts were analyzed regarding demographics, pathology
      findings, and treatment. RESULTS: The diagnosis of benign disease was made in 40
      (78%), borderline in 3 (6%), and malignancy in 7 (14%) patients; however, 1
      patient (2%) had mixed phyllodes with ductal carcinoma in situ. The mean age was
      significantly different for patients with benign disease (33 years) compared with
      those with malignancy (54 years; P < .001). The average tumor size was twice as
      large (11.8 vs 4.1 cm; P = .029) and mitoses were higher with 50% of MPs having
      greater than 5 per 10 high power fields. Although rare, nodal metastasis,
      ulceration, and multicentric disease occurred only in MP. CONCLUSIONS: Among AA
      patients with phyllodes tumors, those with malignant tumors were older and had
      larger tumors and higher mitotic indices than those with benign disease. AA
      patients also displayed some of the more rare features of advanced disease and
      presented with malignancy near the highest reported frequency.

PMID- 25873164
TI  - Altered expression and loss of heterozygosity of the migration and invasion
      inhibitory protein (MIIP) gene in breast cancer.
AB  - Previous studies have characterized the migration and invasion inhibitory protein
      (MIIP) as a novel putative tumor-suppressor gene that regulates cell migration
      and invasion as well as the mitotic checkpoint. The MIIP gene is located on
      chromosome 1p36.22, a common site for deletion in many solid tumors including
      breast cancer. In the present study, we evaluated MIIP expression and allelic
      deletion to gain insight into the role of the MIIP gene in breast cancer. MIIP
      gene mRNA and protein expression was assessed in 86 matched breast cancer and
      adjacent normal tissues. Loss of heterogeneity (LOH) of the MIIP gene was
      determined using single-nucleotide polymorphism (SNP) and microsatellite (MS)
      markers in 149 breast carcinomas and the corresponding normal lymphocytes. The
      analysis revealed that the expression levels of MIIP mRNA and protein were
      downregulated in tumor specimens compared to those in corresponding adjacent
      tissues. Advanced clinical stage and tumor size >2 cm were associated with a
      decreased MIIP expression level. Twenty-six percent (37/142) of tumors were shown
      to have LOH at the MIIP locus by MS and SNP markers. Breast cancer patients with
      LOH at the SNP marker rs2295283 experienced shorter survival time. The attenuated
      expression and LOH of the MIIP gene may contribute to the poor prognosis of
      breast cancer, supporting a tumor-suppressing role of MIIP gene in the
      pathogenesis of this disease.

PMID- 25873165
TI  - Releasing the brakes: targeting FcgammaRIIB on B cells to enhance antibody
      dependent lymphoma immunotherapy.
AB  - The inhibitory Fcgamma receptor modulates therapeutic antibody activity by
      setting a threshold for effector cell activation and removing antibodies from the
      tumor cell surface. In this issue of Cancer Cell, Roghanian and colleagues
      demonstrate that antibodies blocking inhibitory Fcgamma receptor function can
      enhance therapeutic antibody activity to allow optimal tumor cell depletion. 

PMID- 25873166
TI  - FAK to the rescue: activated stroma promotes a "safe haven" for BRAF-mutant
      melanoma cells by inducing FAK signaling.
AB  - Perhaps the most pressing need in cancer therapeutics is to understand drug
      resistance. In this issue of Cancer Cell, Hirata and colleagues show that
      melanoma-associated fibroblasts can drive resistance to the BRAF inhibitor
      PLX4720 by stimulating matrix production/remodeling, and, consequently, survival
      signaling in melanoma cells via beta1-integrin, Src, and FAK. 

PMID- 25873167
TI  - Designed to kill: novel menin-MLL inhibitors target MLL-rearranged leukemia.
AB  - The interaction between menin and oncogenic mixed lineage leukemia (MLL) fusion
      proteins is required for leukemic transformation and may represent a therapeutic
      opportunity. In this issue of Cancer Cell, Borkin and colleagues describe the
      development of highly potent small-molecule inhibitors of this interaction that
      reverse the leukemic phenotype and prolong survival in murine models of MLL
      rearranged leukemia. 

PMID- 25873168
TI  - When one mutation is all it takes.
AB  - In a recent issue of Nature Genetics, Andersson and colleagues report that MLL
      fusion alone may be sufficient to spawn an aggressive leukemia in infants. Some
      other pediatric cancers may share a similar, single, "big-hit" origin, possibly
      reflecting a critical developmental window of stem cell vulnerability. 

PMID- 25873169
TI  - Something in the air: hyperoxic conditioning of the tumor microenvironment for
      enhanced immunotherapy.
AB  - Recent clinical trials in cancer therapy have demonstrated unprecedented
      responses through blockade of CTLA-4 and PD-1 immune checkpoint pathways. In a
      provocative recent paper in Science Translational Medicine, Hatfield and
      colleagues demonstrate the ability of supplemental oxygen to act as a novel
      immune checkpoint inhibitor by disrupting the hypoxia-adenosine-A2aR pathway. 

PMID- 25873170
TI  - Radiotherapy complements immune checkpoint blockade.
AB  - Adaptive immune resistance ablates effective anti-tumor immune responses. In a
      recent issue of Nature, Victor and colleagues describe that anti-PD-L1 combats
      adaptive immune resistance upon localized radiation plus anti-CTLA-4 therapy. The
      superior activity of radiation and dual immune checkpoint blockade is mediated by
      non-redundant immune mechanisms in cancer. 

PMID- 25873171
TI  - Antagonistic human FcgammaRIIB (CD32B) antibodies have anti-tumor activity and
      overcome resistance to antibody therapy in vivo.
AB  - Therapeutic antibodies have transformed cancer therapy, unlocking mechanisms of
      action by engaging the immune system. Unfortunately, cures rarely occur and
      patients display intrinsic or acquired resistance. Here, we demonstrate the
      therapeutic potential of targeting human (h) FcgammaRIIB (CD32B), a receptor
      implicated in immune cell desensitization and tumor cell resistance. FcgammaRIIB
      blocking antibodies prevented internalization of the CD20-specific antibody
      rituximab, thereby maximizing cell surface accessibility and immune effector cell
      mediated antitumor activity. In hFcgammaRIIB-transgenic (Tg) mice, FcgammaRIIB
      blocking antibodies effectively deleted target cells in combination with
      rituximab, and other therapeutic antibodies, from resistance-prone stromal
      compartments. Similar efficacy was seen in primary human tumor xenografts,
      including with cells from patients with relapsed/refractory disease. These data
      support the further development of hFcgammaRIIB antibodies for clinical
      assessment. 

PMID- 25873172
TI  - Synergistic innate and adaptive immune response to combination immunotherapy with
      anti-tumor antigen antibodies and extended serum half-life IL-2.
AB  - Cancer immunotherapies under development have generally focused on either
      stimulating T cell immunity or driving antibody-directed effector functions of
      the innate immune system such as antibody-dependent cell-mediated cytotoxicity
      (ADCC). We find that a combination of an anti-tumor antigen antibody and an
      untargeted IL-2 fusion protein with delayed systemic clearance induces
      significant tumor control in aggressive isogenic tumor models via a concerted
      innate and adaptive response involving neutrophils, NK cells, macrophages, and
      CD8(+) T cells. This combination therapy induces an intratumoral "cytokine storm"
      and extensive lymphocyte infiltration. Adoptive transfer of anti-tumor T cells
      together with this combination therapy leads to robust cures of established
      tumors and development of immunological memory. 

PMID- 25873173
TI  - Mutational cooperativity linked to combinatorial epigenetic gain of function in
      acute myeloid leukemia.
AB  - Specific combinations of acute myeloid leukemia (AML) disease alleles, including
      FLT3 and TET2 mutations, confer distinct biologic features and adverse outcome.
      We generated mice with mutations in Tet2 and Flt3, which resulted in fully
      penetrant, lethal AML. Multipotent Tet2(-/-);Flt3(ITD) progenitors (LSK
      CD48(+)CD150(-)) propagate disease in secondary recipients and were refractory to
      standard AML chemotherapy and FLT3-targeted therapy. Flt3(ITD) mutations and Tet2
      loss cooperatively remodeled DNA methylation and gene expression to an extent not
      seen with either mutant allele alone, including at the Gata2 locus. Re-expression
      of Gata2 induced differentiation in AML stem cells and attenuated leukemogenesis.
      TET2 and FLT3 mutations cooperatively induce AML, with a defined leukemia stem
      cell population characterized by site-specific changes in DNA methylation and
      gene expression. 

PMID- 25873174
TI  - Convergent mutations and kinase fusions lead to oncogenic STAT3 activation in
      anaplastic large cell lymphoma.
AB  - A systematic characterization of the genetic alterations driving ALCLs has not
      been performed. By integrating massive sequencing strategies, we provide a
      comprehensive characterization of driver genetic alterations (somatic point
      mutations, copy number alterations, and gene fusions) in ALK(-) ALCLs. We
      identified activating mutations of JAK1 and/or STAT3 genes in ~20% of 88
      [corrected] ALK(-) ALCLs and demonstrated that 38% of systemic ALK(-) ALCLs
      displayed double lesions. Recurrent chimeras combining a transcription factor
      (NFkB2 or NCOR2) with a tyrosine kinase (ROS1 or TYK2) were also discovered in WT
      JAK1/STAT3 ALK(-) ALCL. All these aberrations lead to the constitutive activation
      of the JAK/STAT3 pathway, which was proved oncogenic. Consistently, JAK/STAT3
      pathway inhibition impaired cell growth in vitro and in vivo.

PMID- 25873175
TI  - AXL mediates resistance to PI3Kalpha inhibition by activating the EGFR/PKC/mTOR
      axis in head and neck and esophageal squamous cell carcinomas.
AB  - Phosphoinositide-3-kinase (PI3K)-alpha inhibitors have shown clinical activity in
      squamous cell carcinomas (SCCs) of head and neck (H&N) bearing PIK3CA mutations
      or amplification. Studying models of therapeutic resistance, we have observed
      that SCC cells that become refractory to PI3Kalpha inhibition maintain PI3K
      independent activation of the mammalian target of rapamycin (mTOR). This
      persistent mTOR activation is mediated by the tyrosine kinase receptor AXL. AXL
      is overexpressed in resistant tumors from both laboratory models and patients
      treated with the PI3Kalpha inhibitor BYL719. AXL dimerizes with and
      phosphorylates epidermal growth factor receptor (EGFR), resulting in activation
      of phospholipase Cgamma (PLCgamma)-protein kinase C (PKC), which, in turn,
      activates mTOR. Combined treatment with PI3Kalpha and either EGFR, AXL, or PKC
      inhibitors reverts this resistance. 

PMID- 25873176
TI  - TGIF governs a feed-forward network that empowers Wnt signaling to drive mammary
      tumorigenesis.
AB  - Many types of human cancers having hyperactivated Wnt signaling display no
      causative alterations in known effectors of this pathway. Here, we report a
      function of TGIF in Wnt signaling. TGIF associates with and diverts Axin1 and
      Axin2 from the beta-catenin destruction complex, therefore allowing beta-catenin
      accrual. Intriguingly, activation of Wnt signaling induces the expression of
      TGIF, which unveils a feed-forward loop that ensures effective integration of Wnt
      signaling. In triple-negative breast cancers (TNBC), elevated levels of TGIF
      correlate with high Wnt signaling and poor survival of patients. Moreover,
      genetic experiments revealed that Tgif1 ablation impeded mammary tumor
      development in MMTV-Wnt1 mice, further underscoring a requirement of TGIF for
      oncogenic Wnt signaling. 

PMID- 25873177
TI  - Intravital imaging reveals how BRAF inhibition generates drug-tolerant
      microenvironments with high integrin beta1/FAK signaling.
AB  - Intravital imaging of BRAF-mutant melanoma cells containing an ERK/MAPK biosensor
      reveals how the tumor microenvironment affects response to BRAF inhibition by
      PLX4720. Initially, melanoma cells respond to PLX4720, but rapid reactivation of
      ERK/MAPK is observed in areas of high stromal density. This is linked to
      "paradoxical" activation of melanoma-associated fibroblasts by PLX4720 and the
      promotion of matrix production and remodeling leading to elevated integrin
      beta1/FAK/Src signaling in melanoma cells. Fibronectin-rich matrices with 3-12
      kPa elastic modulus are sufficient to provide PLX4720 tolerance. Co-inhibition of
      BRAF and FAK abolished ERK reactivation and led to more effective control of BRAF
      mutant melanoma. We propose that paradoxically activated MAFs provide a "safe
      haven" for melanoma cells to tolerate BRAF inhibition. 

PMID- 25873179
TI  - Geometrically unprecedented 3-, 5- and 7-membered Hg(II)-Cu(I) and Hg(II)-Ag(I)
      thiolate clusters: precursors to intermetallics.
AB  - The syntheses of three polynuclear heterobimetallic complexes through the use of
      a homoleptic mercuric thiolate anion as a template for the assembly of coinage
      metal are presented. The complexes, [(PPh3)3Ag3(MU-SPh)7Hg2] (1), [Hg(MU
      SPh)4{Cu(PPh3)2}2] (2) and [(dppe)2Cu5(MU-SPh)7Hg2(SPh)2] (3) were utilized as
      precursors for the fabrication of Hg-Ag and Hg-Cu intermetallics.

PMID- 25873178
TI  - Behavioural effects of fetal antidepressant exposure in a Norwegian cohort of
      discordant siblings.
AB  - OBJECTIVE: Potential adverse effects of prenatal antidepressant exposure on child
      development are still debated. The possibility that associations are due to
      genetic or familial environmental risk factors rather than antidepressant use per
      se cannot easily be ruled out in conventional studies. Our objective was
      therefore to evaluate the association between prenatal antidepressant exposure
      and behavioural problems in a sibling controlled study. METHOD: This study used
      data on 20 180 siblings identified from the population-based Norwegian Mother and
      Child Cohort Study recruited between 1999 and 2008. The mothers were asked to
      report antidepressant use at gestational weeks 17 and 30 and 6 months post
      partum. Child Behavioral Checklist syndrome scales were used to assess
      externalizing and internalizing behavioural problems by questionnaires sent to
      mothers at 18 and 36 months postpartum. We performed unmatched and matched
      sibling analyses using both random- and fixed-effects linear models,
      respectively, to determine potential behavioural effects of antidepressant
      exposure. RESULTS: Prenatal exposure to antidepressants was associated with
      increased levels of anxiety symptoms in 3 year old children after adjusting for
      maternal familial effects and confounding by indication (i.e. maternal
      depression). Effect of prenatal exposure to antidepressants was specific to
      anxiety, and not associated with emotional reactivity, somatic complaints, sleep
      problems, attention problems or aggression. CONCLUSION: Using a sibling design,
      we showed that prenatal antidepressant use was specifically associated with
      increased anxiety symptoms after adjusting for maternal familial factors and
      confounding by indication.

PMID- 25873180
TI  - Epilepsy and deprivation, a data linkage study.
AB  - OBJECTIVE: To investigate whether the link between epilepsy and deprivation is
      due to factors associated with deprivation (social causation) or factors
      associated with a diagnosis of epilepsy (social drift). METHODS: We reviewed
      electronic primary health care records from 2004 to 2010, identifying prevalent
      and incident cases of epilepsy and recording linked deprivation scores. Logistic
      and Poisson regression models were used to calculate odds ratios and incidence
      rate ratios. The change in deprivation was measured 10 years after the initial
      diagnosis of epilepsy for a cohort of people. RESULTS: Between 2004 and 2010, 8.1
      million patient-years of records were reviewed. Epilepsy prevalence and incidence
      were significantly associated with deprivation. Epilepsy prevalence ranged from
      1.13% (1.07-1.19%) in the most deprived decile to 0.49% (0.45-0.53%) in the least
      deprived decile (adjusted odds ratio 0.92, p < 0.001). Epilepsy incidence ranged
      from 40/100,000 per year in the most deprived decile to 19/100,000 per year in
      the least deprived decile (adjusted incidence rate ratio 0.94, p < 0.001). There
      was no statistically significant change in deprivation index decile 10 years
      after a new diagnosis of epilepsy (mean difference -0.04, p = 0.85).
      SIGNIFICANCE: Epilepsy prevalence and incidence are strongly associated with
      deprivation; the deprivation score remains unchanged 10 years after a diagnosis
      of epilepsy. These findings suggest that increasing rates of epilepsy in deprived
      areas are more likely explained by social causation than by social drift. The
      nature of the association between incident epilepsy and social deprivation needs
      further exploration.

PMID- 25873181
TI  - Hot executive function following moderate-to-late preterm birth: altered delay
      discounting at 4 years of age.
AB  - Interest in monitoring long-term neurodevelopmental outcomes of children born
      moderate-to-late preterm (32-36 weeks gestation) is increasing. Moderate-to-late
      preterm birth has a negative impact on academic achievement, which may relate to
      differential development of executive function (EF). Prior studies reporting
      deficits in EF in preterm children have almost exclusively assessed EF in
      affectively neutral contexts in high-risk preterm children (< 32 weeks
      gestation). Disrupted function in motivational or emotionally charged contexts
      (hot EF) following preterm birth remains uninvestigated, despite evidence that
      preterm children show differential development of neural circuitry subserving hot
      EF, including reduced orbitofrontal cortex volume. The present study is the first
      to examine whether low-risk, healthy children born moderate-to-late preterm
      exhibit impairments in the development of hot EF. Preterm children at age 4.5
      years were less likely to choose larger, delayed rewards across all levels of
      reward magnitude on a delay discounting task using tangible rewards, but
      performed more similarly to their full-term peers on a delay aversion task
      involving abstract rewards and on measures of cool EF. The relationship between
      gestational age at birth and selection of delayed rewards extended across the
      entire gestational age range of the sample (32-42 weeks), and remained
      significant after controlling for intelligence and processing speed. Results
      imply that there is not a finite cut-off point at which children are spared from
      potential long-term neurodevelopmental effects of PT birth. Further investigation
      of reward processing and hot EF in individuals with a history of PT birth is
      warranted given the susceptibility of prefrontal cortex development to early
      environmental variations.

PMID- 25873182
TI  - Clinical and audiological findings in children with acute otitis media.
AB  - CONCLUSION: It is recommended to perform follow-up tympanometry and if necessary
      tonal audiometry in children who have normal plain otoscopy findings after
      recovering from acute otitis media (AOM). Children with Type B tympanogram, 3
      months following the onset of AOM, are very likely to have a conductive hearing
      loss. Type B tympanogram is a much better indicator of effusion in the middle ear
      compared to plain otoscopy. OBJECTIVE: This study was undertaken to investigate
      the frequency and duration of middle ear effusion in children following an
      episode of acute otitis media, to track changes in tonal audiometry and
      tympanometry findings in the post-AOM period, and recognize the optimal timing
      for performing both tests. METHODS: In this study, 125 children aged 5-7 years
      with bilateral AOM were randomly selected and separately followed up for 3
      months. The children underwent six ear, nose, and throat (ENT 1-6) examinations,
      six tympanometries (TM 1-6), and three tonal audiometries (TA 1-3). Evaluation of
      nasopharynx was done at the ENT 1 examination. Children who received ventilation
      tubes were followed for 21 month altogether. RESULTS: At the first otoscopy,
      pathological findings were recorded in 250 ears/125 children (100.0%). The number
      of pathological otoscopy findings decreased at each subsequent examination. At
      ENT 6 all children had normal otoscopy findings. Type B tympanogram was detected
      in 49/250 (19.6%) ears at TM 6, performed 3 months following the onset of the
      disease. At the TA 1 conductive hearing impairment was recorded in 158/250
      (63.2%) ears, at TA 2 in 66/250 (26.4%), and at TA 3 in 39/250 (15.6%). Most of
      them were associated with Type B tympanogram.

PMID- 25873183
TI  - Electromagnetohydrodynamic (EMHD) flow between two transversely wavy
      microparallel plates.
AB  - In this paper, 2D electromagnetohydrodynamic (EMHD) flow in a microparallel
      channel with slightly transverse corrugated walls is investigated using
      perturbation method. The corrugations of the two walls are presented by periodic
      sinusoidal waves with small amplitudes. The perturbation solutions of the stream
      function and a relation between flow rate and roughness are obtained. It is shown
      that the flow rate always decreases due to the wall corrugations irrespective of
      the phase difference. For prescribed Hartmann number and wave number of the wavy
      walls, the flow resistance increases as the phase difference between the wall
      corrugations increases. The effect of corrugation on the flow rate decreases with
      Hartmann number. With the increase of wave number, the effects of corrugations on
      the flow rate increase. The phase difference of wall corrugations becomes
      unimportant when the wave number is greater than 4. The obtained results for the
      flow rates as a function of the applied current are in qualitative agreement with
      the existing experimental results. 

PMID- 25873185
TI  - Gold(I)-catalyzed hydroindolylation of allenyl ethers.
AB  - The gold(i)-catalyzed reaction/rearrangement of allenyl ethers has been
      investigated in the presence of indoles. Either hydroindolylation or alkylation
      of an indole with the pendant group of allenyl ether has been observed. The
      reaction outcome seems to be decided mainly by the nature of the pendant group of
      the allenyl ether. Control experiments are indicative of an inner sphere
      mechanism for the hydroindolylation reaction. 

PMID- 25873186
TI  - Postsynthetic Improvement of the Physical Properties in a Metal-Organic Framework
      through a Single Crystal to Single Crystal Transmetallation.
AB  - A single crystal to single crystal transmetallation process takes place in the
      three-dimensional (3D) metal-organic framework (MOF) of formula Mg(II) 2 {Mg(II)
      4 [Cu(II) 2 (Me3 mpba)2 ]3 }?45 H2 O (1; Me3 mpba(4-) =N,N'-2,4,6-trimethyl-1,3
      phenylenebis(oxamate)). After complete replacement of the Mg(II) ions within the
      coordination network and those hosted in the channels by either Co(II) or Ni(II)
      ions, 1 is transmetallated to yield two novel MOFs of formulae Co2 (II) {Co(II) 4
      [Cu(II) 2 (Me3 mpba)2 ]3 }?56 H2 O (2) and Ni2 (II) {Ni(II) 4 [Cu(II) 2 (Me3
      mpba)2 ]3 }? 54 H2 O (3). This unique postsynthetic metal substitution affords
      materials with higher structural stability leading to enhanced gas sorption and
      magnetic properties. 

PMID- 25873187
TI  - Maternal folic acid supplementation trends 2009-2013.
AB  - OBJECTIVE: We analyzed trends in folic acid supplementation among women booking
      for antenatal care between 2009 and 2013. DESIGN: Prospective observational
      study. SETTING: Large university teaching hospital. POPULATION: We included all
      women who delivered an infant >=500 g from 1 January 2009 to 31 December 2013.
      METHODS: Body mass index was calculated using early pregnancy weight and height
      measured at first antenatal visits. Sociodemographic and clinical data were
      gathered prospectively. Multivariate logistic regression analyses were applied to
      determine the correlates of periconceptional folic acid supplementation. MAIN
      OUTCOME MEASURES: Rates and correlates of folic acid supplementation. RESULTS: Of
      42 362 women, 99.2% (n = 42 042) were suitable for analysis. The mean age was
      30.7 years and mean body mass index was 25.6 kg/m(2) , 40.7% (n = 17 054) were
      primigravidas and 70.6% (n = 29 741) were Irish-born. Overall, 43.9% (n = 18 473)
      took periconceptional (preconceptional and postconceptional) folic acid, 49.4% (n
      = 20 782) took postconceptional folic acid only, and 6.6% (n = 2787) took no
      folic acid. The women most likely to take folic acid were those who planned their
      pregnancy and were >30 years old, non-obese, Irish-born and employed
      professionally. The periconceptional folic acid rate decreased from 45.1% in 2009
      to 43.1% in 2013 (p = 0.01). Over five years, periconceptional folic acid
      supplementation decreased among women who were multiparous (43.8-41.6%, p =
      0.02), aged 30-39 years (58.9-55.0%, p < 0.001), Irish-born (50.1-47.1%, p <
      0.001) and obese (38.6-36.9%, p = 0.02). CONCLUSION: Overall, the rate of
      periconceptional folic acid supplementation decreased in the five years 2009
      2013, particularly among women who were multiparous, aged 30-39 years, Irish-born
      and obese.

PMID- 25873188
TI  - Example of retrospective dataset publication through Dryad.

PMID- 25873190
TI  - Portable and visual electrochemical sensor based on the bipolar light emitting
      diode electrode.
AB  - Here we report a novel sensing strategy based on the closed bipolar system, in
      which we utilize a light emitting diode (LED) to connect a split bipolar
      electrode (BPE) and generate the luminescent signal in the presence of the
      target. With this design, we have constructed a BPE array for the quick and high
      throughput determination of various electroactive substances with naked eyes. Due
      to the ultrahigh current efficiency of the closed bipolar system, the sample
      concentration can be reported by the luminous intensity of the inserted LED
      without the expensive luminescent agent and instruments. Besides, the stability
      of the signal is improved because of the electroluminescent property of the LED.
      To demonstrate the promising applications of the bipolar LED electrode (BP-LED
      E), the rapid quantification of four model targets (H2O2, ascorbic acid (AA),
      glucose, and blood sugar) has been achieved based on different principles. 

PMID- 25873191
TI  - 2014 global prescription medication statistics: strong growth and CNS well
      represented.

PMID- 25873189
TI  - Cardiac rehabilitation versus standard care after aortic aneurysm repair
      (Aneurysm CaRe): study protocol for a randomised controlled trial.
AB  - BACKGROUND: Abdominal and thoracic aortic aneurysms (A/TAA) are an important
      cause of mortality amongst the older population. Although A/TAA repair can be
      performed with low peri-operative risk, overall life expectancy remains poor in
      the years that follow surgery. The majority of deaths are caused by heart attack
      or stroke, which can both be prevented by cardiac rehabilitation (CR) in patients
      with clinically-manifest coronary artery disease. A Cochrane review has urged
      researchers to widen the use of CR to other populations with severe
      cardiovascular risk, and patients surviving A/TAA repair appear ideal candidates.
      However, it is unknown whether CR is feasible or acceptable to A/TAA patients,
      who are a decade older than those currently enrolling in CR. Aneurysm-CaRe is a
      feasibility randomised controlled trial (RCT) that will address these issues.
      METHODS AND DESIGN: Aneurysm-CaRe is a pilot RCT of CR versus standard care after
      A/TAA repair, with the primary objectives of estimating enrolment to a trial of
      CR after A/TAA repair and estimating compliance with CR amongst patients with
      A/TAA. Aneurysm-CaRe will randomise 84 patients at two sites. Patients discharged
      from hospital after elective A/TAA repair will be randomised to standard care or
      enrolment in their local CR programme with a protocolised approach to medical
      cardiovascular risk reduction. The primary outcome measures are enrolment in the
      RCT and compliance with CR. Secondary outcomes will include phenotypic markers of
      cardiovascular risk and smoking cessation, alongside disease-specific and generic
      quality-of-life measures. TRIAL REGISTRATION: ISRCTN 65746249 5 June 2014.

PMID- 25873193
TI  - Tuned red NIR phosphorescence of polyurethane hybrid composites embedding
      metallic nanoclusters for oxygen sensing.
AB  - Polyurethane nanocomposites with high content of red NIR luminescent transition
      metal clusters are presented. The gas permeability of the hybrid material is
      controlled by adjusting the hard/soft segment ratio of the organic matrix
      structure leading to a drastic and reversible enhancement of cluster luminescence
      depending on the molecular oxygen concentration in its surrounding atmosphere. 

PMID- 25873194
TI  - Connectivity-based parcellation of the thalamus in multiple sclerosis and its
      implications for cognitive impairment: A multicenter study.
AB  - In this multicenter study, we performed a tractography-based parcellation of the
      thalamus and its white matter connections to investigate the relationship between
      thalamic connectivity abnormalities and cognitive impairment in multiple
      sclerosis (MS). Dual-echo, morphological and diffusion tensor (DT) magnetic
      resonance imaging (MRI) scans were collected from 52 relapsing-remitting MS
      patients and 57 healthy controls from six European centers. Patients underwent an
      extensive neuropsychological assessment. Thalamic connectivity defined regions
      (CDRs) were segmented based on their cortical connectivity using diffusion
      tractography-based parcellation. Between-group differences of CDRs and cortico
      thalamic tracts DT MRI indices were assessed. A vertex analysis of thalamic shape
      was also performed. A random forest analysis was run to identify the best imaging
      predictor of global cognitive impairment and deficits of specific cognitive
      domains. Twenty-two (43%) MS patients were cognitively impaired (CI). Compared to
      cognitively preserved, CI MS patients had increased fractional anisotropy of
      frontal, motor, postcentral and occipital connected CDRs (0.002<P<0.02). They
      also experienced more pronounced atrophy in anterior thalamic regions and
      abnormal DT MRI indices of all cortico-thalamic tracts. Damage of specific
      cortico-thalamic tracts explained global cognitive dysfunction and impairment of
      selected cognitive domains better than all other MRI variables. Thalamic CDR DT
      MRI abnormalities were correlated with abnormalities of the corresponding cortico
      thalamic tracts. Cortico-thalamic disconnection is, at various levels, implicated
      in cognitive dysfunction in MS. Thalamic involvement in CI MS patients is likely
      related to gray matter rather than white matter damage of thalamic subregions.

PMID- 25873195
TI  - Monte Carlo-based assessment of the trade-off between spatial resolution, field
      of-view and scattered radiation in the variable resolution X-ray CT scanner.
AB  - OBJECTIVE: The purpose of this work is to evaluate the impact of optimization of
      magnification on performance parameters of the variable resolution X-ray (VRX) CT
      scanner. METHODS: A realistic model based on an actual VRX CT scanner was
      implemented in the GATE Monte Carlo simulation platform. To evaluate the
      influence of system magnification, spatial resolution, field-of-view (FOV) and
      scatter-to-primary ratio of the scanner were estimated for both fixed and optimum
      object magnification at each detector rotation angle. Comparison and inference
      between these performance parameters were performed angle by angle to determine
      appropriate object position at each opening half angle. RESULTS: Optimization of
      magnification resulted in a trade-off between spatial resolution and FOV of the
      scanner at opening half angles of 90 degrees -12 degrees , where the spatial
      resolution increased up to 50% and the scatter-to-primary ratio decreased from
      4.8% to 3.8% at a detector angle of about 90 degrees  for the same FOV and X-ray
      energy spectrum. The disadvantage of magnification optimization at these angles
      is the significant reduction of the FOV (up to 50%). Moreover, magnification
      optimization was definitely beneficial for opening half angles below 12 degrees 
      improving the spatial resolution from 7.5 cy/mm to 20 cy/mm. Meanwhile, the FOV
      increased by more than 50% at these angles. CONCLUSION: It can be concluded that
      optimization of magnification is essential for opening half angles below 12
      degrees . For opening half angles between 90 degrees  and 12 degrees , the VRX CT
      scanner magnification should be set according to the desired spatial resolution
      and FOV.

PMID- 25873196
TI  - Investigating in-field and out-of-field neutron contamination in high-energy
      medical linear accelerators based on the treatment factors of field size, depth,
      beam modifiers, and beam type.
AB  - PURPOSE: We analysed the effects of field size, depth, beam modifier and beam
      type on the amount of in-field and out-of-field neutron contamination for medical
      linear accelerators (linacs). METHODS: Measurements were carried out for three
      high-energy medical linacs of Elekta Synergy Platform, Varian Clinac DHX High
      Performance and Philips SL25 using bubble detectors. The photo-neutron
      measurements were taken in the first two linacs with 18 MV nominal energy,
      whereas the electro-neutrons were measured in the three linacs with 9 MeV, 10
      MeV, 15 MeV and 18 MeV. RESULTS: The central neutron doses increased with larger
      field sizes as a dramatic drop off was observed in peripheral areas. Comparing
      with the jaws-shaped open-field of 10 * 10 cm, the motorised and physical wedges
      contributed to neutron contamination at central axis by 60% and 18%,
      respectively. The similar dose increment was observed in MLC-shaped fields. The
      contributions of MLCs were in the range of 55-59% and 19-22% in Elekta and Varian
      linacs comparing with 10 * 10 and 20 * 20 cm open fields shaped by the jaws,
      respectively. The neutron doses at shallow depths were found to be higher than
      the doses found at deeper regions. The electro-neutron dose at the 18 MeV energy
      was higher than the doses at the electron energies of 15 MeV and 9 MeV by a
      factor of 3 and 50, respectively. CONCLUSION: The photo- and electro-neutron dose
      should be taken into consideration in the radiation treatment with high photon
      and electron energies.

PMID- 25873198
TI  - Reporting Organ Trafficking Networks: A Survey-Based Plea to Breach the Secrecy
      Oath.
AB  - Patients travel worldwide to purchase kidneys. Transplant professionals can play
      a role in identifying kidney purchase. However, due to the tension between their
      rights and obligations, a lack of understanding and knowledge exists on how to
      prevent and report purchase. We present the results of a national survey that
      describes transplant professionals' experiences, attitudes, behaviors, conflicts
      of duties, legal knowledge and needs for guidelines toward patients who purchase
      kidneys abroad. Second, we clarify professionals' rights and obligations
      regarding organ purchase and propose actions that they can take to report
      purchase. Of the 100/241 (42%) professionals who treated patients who traveled to
      a country outside the European Union for a kidney transplant, 31 (31%) were
      certain that patients purchased kidneys. Sixty-five (65%) had suspicions that
      patients had bought kidneys. The majority reported a conflict of duties. Eighty
      percent reported a need for guidelines. Professionals can help prevent organ
      purchase by disclosing information about organ trafficking networks to law
      enforcement. Such disclosure can support the investigation and prosecution of
      networks. We offer key components for guidelines on disclosure of these networks.

PMID- 25873197
TI  - Endocannabinoids mediate bidirectional striatal spike-timing-dependent
      plasticity.
AB  - KEY POINTS: Although learning can arise from few or even a single trial, synaptic
      plasticity is commonly assessed under prolonged activation. Here, we explored the
      existence of rapid responsiveness of synaptic plasticity at corticostriatal
      synapses in a major synaptic learning rule, spike-timing-dependent plasticity
      (STDP). We found that spike-timing-dependent depression (tLTD) progressively
      disappears when the number of paired stimulations (below 50 pairings) is
      decreased whereas spike-timing-dependent potentiation (tLTP) displays a biphasic
      profile: tLTP is observed for 75-100 pairings, is absent for 25-50 pairings and
      re-emerges for 5-10 pairings. This tLTP induced by low numbers of pairings (5-10)
      depends on activation of the endocannabinoid system, type-1 cannabinoid receptor
      and the transient receptor potential vanilloid type-1. Endocannabinoid-tLTP may
      represent a physiological mechanism operating during the rapid learning of new
      associative memories and behavioural rules characterizing the flexible behaviour
      of mammals or during the initial stages of habit learning. ABSTRACT: Synaptic
      plasticity, a main substrate for learning and memory, is commonly assessed with
      prolonged stimulations. Since learning can arise from few or even a single trial,
      synaptic strength is expected to adapt rapidly. However, whether synaptic
      plasticity occurs in response to limited event occurrences remains elusive. To
      answer this question, we investigated whether a low number of paired stimulations
      can induce plasticity in a major synaptic learning rule, spike-timing-dependent
      plasticity (STDP). It is known that 100 pairings induce bidirectional STDP, i.e.
      spike-timing-dependent potentiation (tLTP) and depression (tLTD) at most central
      synapses. In rodent striatum, we found that tLTD progressively disappears when
      the number of paired stimulations is decreased (below 50 pairings) whereas tLTP
      displays a biphasic profile: tLTP is observed for 75-100 pairings, absent for 25
      50 pairings and re-emerges for 5-10 pairings. This tLTP, induced by very few
      pairings (~5-10) depends on the endocannabinoid (eCB) system. This eCB-dependent
      tLTP (eCB-tLTP) involves postsynaptic endocannabinoid synthesis, requires paired
      activity (post- and presynaptic) and the activation of type-1 cannabinoid
      receptor (CB1R) and transient receptor potential vanilloid type-1 (TRPV1). eCB
      tLTP occurs in both striatopallidal and striatonigral medium-sized spiny neurons
      (MSNs) and is dopamine dependent. Lastly, we show that eCB-LTP and eCB-LTD can be
      induced sequentially in the same neuron, depending on the cellular conditioning
      protocol. Thus, while endocannabinoids are usually thought simply to depress
      synaptic function, they also constitute a versatile system underlying
      bidirectional plasticity. Our results reveal a novel form of synaptic plasticity,
      eCB-tLTP, which may underlie rapid learning capabilities characterizing
      behavioural flexibility.

PMID- 25873199
TI  - Assessment of the embryotoxicity of four Chinese herbal extracts using the
      embryonic stem cell test.
AB  - Rhizoma Atractylodes macrocephala, Radix Isatidis, Coptis chinensis and Flos
      Genkwa are common herbal remedies used by pregnant woman in China. In this study,
      their potential embryotoxicity was assessed using the embryonic stem cell test
      (EST) and a prediction model. The potential embryotoxicity of the herbs was based
      on three endpoints: the concentrations of the compounds that inhibited the
      proliferation of 50% of embryonic stem cells (ESCs) (IC50ES), the concentrations
      that inhibited 50% of 3T3 cells (IC503T3), and the concentrations that inhibited
      the differentiation of 50% of ESCs (ID50ES). The results revealed that Rhizoma
      Atractylodes macrocephala and Radix Isatidis are non-embryotoxic compounds.
      Coptis chinensis extracts appeared to demonstrated weak embryotoxicity, and Flos
      Genkwa exhibited strong embryotoxicity. These results may be useful in guiding
      the clinical use of these herbs and in expanding the application of the EST to
      the field of traditional Chinese medicine.

PMID- 25873200
TI  - Effects of short RNA structural analogues against hepatitis C virus genotypes 2,
      3 and 4 in replicon cells.
AB  - OBJECTIVE: To determine whether computer-predicted short RNA structural analogues
      could inhibit hepatitis C virus (HCV) genotype 2a, 3a and 4a replication in
      cultured cells. METHODS: Short RNA sequences, X12, X12a and X12b, designed to be
      identical in secondary structure to the X region in the 3'-untranslated region
      (3'-UTR) of the HCV 1b genome, as well as shorter stem-loop components of X
      region, were inserted into a plasmid and transfected into separate Huh7.5 human
      hepatoma cells stably transfected with subgenomic replicons for genotypes 2a, 3a
      and 4a. All replicons included a firefly luciferase reporter gene. After 48 h of
      plasmid transfection, the inhibition of HCV replication was determined by HCV RNA
      isolation and quantification by real-time polymerase chain reaction and
      luciferase assays. RESULTS: All the secondary structural analogues to genotype 1b
      X region cross-inhibited genotype 2a, 3a and 4a replicons. The maximum inhibition
      by genotype 1b X region structural analogues was obtained against genotype 2a
      cells in which X12, X12a and X12b inhibited replication by 30%, 63% and 72%,
      respectively (P < 0.05 for all), compared to an unrelated hepatitis B viral
      analogue. CONCLUSIONS: Despite substantial sequence dissimilarity, HCV RNA
      genotype 1b X region analogues cross-inhibited the replication of HCV genotypes
      2a, 3a and 4a. Particular conformations and not the sequence of the stem-loops of
      the X region are involved in HCV replication.

PMID- 25873201
TI  - TTF-1 and napsin A on cell blocks and supernatants of pleural fluids for labeling
      malignant effusions.
AB  - In this retrospective study of 80 pleural effusions, the combination of thyroid
      transcription factor 1 (TTF-1) and napsin A immunostaining on fluid cell blocks
      was positive in 80% of lung adenocarcinomas. Although measuring TTF-1 pleural
      fluid concentrations was of no value, quantification of napsin A levels allowed
      the identification of one third of the double-negative stained lung
      adenocarcinomas, with an overall accuracy similar to classical tumour markers for
      malignant-benign discrimination (sensitivity 40%, specificity 100%). 

PMID- 25873202
TI  - Expression of hMOF, but not HDAC4, is responsible for the global histone H4K16
      acetylation in gastric carcinoma.
AB  - Increasing evidence suggests that the alteration of global histone H4K16
      acetylation (H4K16ac) may be involved in several types of cancer. It is known
      that the global histone H4K16ac level in cells is controlled by several enzymes
      including histone acetyltransferases (HATs) and histone deacetylases (HDACs). We
      report in detail which particular enzyme is responsible for global reduction of
      histone H4K16ac in gastric cancer. Our study included 156 frozen tissue samples
      of primary diagnosed gastric cancer tissues and matched adjacent or normal
      tissues, and the gastric cancer cells SGC-7901 and MGC-803. The reverse
      transcription polymerase chain reaction (RT-PCR), western blot, transient
      transfection and siRNA knockdown approaches were used. Statistical analysis of
      the qRT-PCR data revealed that a significant reduction (>2-fold decreased) of
      hMOF expression in gastric cancer tissues in 81% (42/52) of patients. In patients
      with gastric cancer, downregulation of hMOF was connected to gastric cancer and
      tissues with pT2-T4 tumor status, lymph node metastasis and distant metastasis.
      Overall survival rates revealed a significant difference between the low- and
      high-hMOF expression groups. However, there was no significant difference by age,
      gender and cell differentiation. In SGC-7901 and MGC-803 gastric cancer cells, as
      expected, low expression of hMOF and decreased global histone H4K16ac were
      observed. Although we did not obtained a statistically significant high-level of
      HDAC4 in tumor tissues, increased HDAC4 in both gastric cancer cell lines was
      detected. Therefore, overexpression of hMOF and knockdown of HDAC4 experiments
      were carried out to investigate the potential coordinating role between hMOF and
      HDAC4 on global histone H4K16ac in gastric cancer. Overexpression of hMOF
      increased global H4K16ac in cells, however, no obvious increase of global H4K16ac
      in HDAC4 knockdown MGC-803 cells was observed. Histone acetyltransferase hMOF and
      global histone H4K16ac status might be involved in gastric cancer tumorigenic
      pathways. hMOF, but not HDAC4, is mainly responsible for global histone H4K16ac
      acetylation in gastric cancer cells.

PMID- 25873203
TI  - Clinical audit results in earlier nutritional intervention in malnourished
      children with cystic fibrosis with improved outcome.
AB  - AIM: The association between nutritional status, pulmonary function and survival
      in cystic fibrosis (CF) is well established. A previous case series from the
      Royal Children's Hospital, Melbourne (RCH), demonstrated suboptimal referral
      practices and highlighted the importance of early nutritional interventions in
      children with CF. Various qualitative changes were made to our CF service, and
      this study assesses the effects of these practice changes timing of gastrostomy
      and clinical outcome in patients who underwent gastrostomy insertion. METHOD:
      Clinical audit of all CF patients who had undergone gastrostomy insertion from
      2002 to 2010 at Royal Children's Hospital. Clinical data, including nutritional
      parameters, respiratory function and survival, were collected at 2 years prior
      and 2 years post gastrostomy insertion. Data were compared with the previous
      study from 1989 to 1997. RESULTS: Patients with CF who underwent gastrostomy
      insertion between 2002 and 2010 (n = 22) had higher weight-for-age scores (-1.5
      +/- 0.68 vs. -2.67 +/- 1.06; P = 0.0001) and higher forced expiratory volume in 1
      s (68% +/- 22 vs. 52% +/- 18.5; P = 0.006), compared with the cohort from 1989 to
      1997 (n = 37). These differences were maintained at 2-year follow-up. Pseudomonas
      aeruginosa colonisation rate was 100% in 1989-1997 vs. 41% in 2002-2010; P =
      0.0001. The 2-year survival post-gastrostomy insertion improved from 70% to 100%;
      P = 0.004. CONCLUSION: Earlier referral of patients in the recent cohort resulted
      in sustained improvements in weight-for-age and lung function. Survival at 2
      years post-procedure was significantly improved. This study confirms the value of
      clinical audits and subsequent re-evaluation of clinical services.

PMID- 25873204
TI  - High-performance graphene/sulphur electrodes for flexible Li-ion batteries using
      the low-temperature spraying method.
AB  - Elementary sulphur (S) has been shown to be an excellent cathode material in
      energy storage devices such as Li-S batteries owing to its very high capacity.
      The major challenges associated with the sulphur cathodes are structural
      degradation, poor cycling performance and instability of the solid-electrolyte
      interphase caused by the dissolution of polysulfides during cycling. Tremendous
      efforts made by others have demonstrated that encapsulation of S materials
      improves their cycling performance. To make this approach practical for large
      scale applications, the use of low-cost technology and materials has become a
      crucial and new focus of S-based Li-ion batteries. Herein, we propose to use a
      low temperature spraying process to fabricate graphene/S electrode material,
      where the ink is composed of graphene flakes and the micron-sized S particles
      prepared by grinding of low-cost S powders. The S particles are found to be well
      hosted by highly conductive graphene flakes and consequently superior cyclability
      (~70% capacity retention after 250 cycles), good coulombic efficiency (~98%) and
      high capacity (~1500 mA h g(-1)) are obtained. The proposed approach does not
      require high temperature annealing or baking; hence, another great advantage is
      to make flexible Li-ion batteries. We have also demonstrated two types of
      flexible batteries using sprayed graphene/S electrodes. 

PMID- 25873205
TI  - Serum brain-derived neurotrophic factor levels in relation to comorbid depression
      and cytokine levels in Nepalese men with alcohol-use disorders.
AB  - Neurodegenerative and inflammatory processes are involved separately in major
      depression (MD) and alcohol-use disorders (AUD). Little is known about the nature
      of this relationship in the context of comorbid AUD and depression disorders. In
      this study, we determined brain-derived neurotrophic factor (BDNF) serum levels
      in patients with AUD and tested whether BDNF levels were related to history of
      major depression, recent depressive symptoms, AUD severity, and TNF-alpha and IL
      6 levels. Nepalese male AUD inpatients (N=152) abstinent from alcohol for an
      average of 34 days were administered structured interviews to assess depression
      symptoms and pattern and extent of alcohol use, and to generate research
      diagnoses for AUD and MD. AUD severity was assessed by scores on the Alcohol Use
      Disorder Identification Test. Serum BDNF and cytokines were measured using ELISA
      and multiplex technology, respectively. Although serum BDNF levels were unrelated
      to MD history, patients with recent depressive symptoms (n=42) had lower (mean+/
      SD) BDNF serum levels compared to those without (n=110) (21.6+/-8.1 ng/mL vs.
      26.0+/-9.6 ng/mL; p=0.010), and patients with higher AUD severity and binge
      drinking patterns had higher mean serum BDNF levels compared to lower AUD
      severity and non-binging (25.9+/-9.7 ng/mL vs. 22.1+/-8.7 ng/mL; p=0.022 and
      25.7+/-9.3 vs. 21.8+/-9.7 ng/mL; p=0.029, respectively). Positive correlations
      were present between BDNF and TNF-alpha (r=0.39, p<0.001) and IL-6 (r=0.2,
      p=0.027). In particular, TNF-alpha levels were predictive of BDNF levels after
      controlling for confounders (B=0.3 [95% CI=0.2-0.5], p<0.001). These findings
      show that in alcohol-using populations, peripheral BDNF levels are related to
      severity of AUD as well as presence of depressive symptoms. The significant
      associations between inflammatory and neurotrophic factors may have implications
      for neuroadaptive changes during recovery from AUD.

PMID- 25873206
TI  - Studies on the regulation of transient lower esophageal sphincter relaxations
      (TLESRs) by acid in the esophagus and stomach.
AB  - Transient lower esophageal sphincter relaxation (TLESR) is the major mechanism of
      gastroesophageal reflux, but the regulation of TLESR by stimuli in the esophagus
      is incompletely understood. We have recently reported that acid infusion in the
      esophagus substantially (by 75%) increased the number of meal-induced TLESR in
      healthy subjects. We concluded that the TLESR reflex triggered by gastric
      distention with meal was enhanced by the stimulation of esophageal nerves by
      acid. However, the possibilities that the acid infused into the esophagus acts
      after passing though lower esophageal sphincter in stomach to enhance TLESR, or
      that the acid directly initiates TLESR from the esophagus were not addressed.
      Here, we evaluated the effect of acid infusion into the proximal stomach on meal
      induced TLESR (study 1) and the ability of acid infusion into the esophagus to
      initiate TLESR without prior meal (study 2). We analyzed TLESRs by using high
      resolution manometry in healthy subjects in paired randomized studies. In study
      1, we found that acid infusion into the proximal stomach did not affect TLESRs
      induced by standard meal. The number of meal-induced TLESRs following the acid
      infusion into the proximal stomach was similar to the number of meal-induced
      TLESRs following the control infusion. In study 2, we found that acid infusion
      into the esophagus without prior meal did not initiate TLESRs. We conclude that
      the increase in the meal-induced TLESRs by acid in the esophagus demonstrated in
      our previous study is not attributable to the action of acid in the stomach or to
      direct initiation of TLESR from the esophagus by acid. Our studies are consistent
      with the concept that the stimuli in the esophagus can influence TLESRs. The
      enhancement of TLESR by acid in the esophagus may contribute to pathogenesis of
      gastroesophageal reflux in some patients. 

PMID- 25873208
TI  - Diffusion kurtosis imaging predicts neoadjuvant chemotherapy responses within 4
      days in advanced nasopharyngeal carcinoma patients.
AB  - PURPOSE: To explore the clinical value of diffusion kurtosis imaging (DKI) and
      monoexponential diffusion-weighted imaging (DWI) for predicting early response to
      neoadjuvant chemotherapy (NAC) in patients with nasopharyngeal carcinoma (NPC).
      MATERIALS AND METHODS: Fifty-nine patients with stage III-IVb NPC underwent four
      3.0T MR scans: prior to, and on the 4th, 21st, 42nd days after NAC initiation.
      The parameters of DKI (corrected diffusion coefficient, D; excess diffusion
      kurtosis coefficient, K) and monoexponential DWI (apparent diffusion coefficient,
      ADC) were obtained at the first three scans. Statistical methods included
      Student's t-test or Mann-Whitney U-test, receiver operating characteristic (ROC)
      curve analyses and paired X(2) test. RESULTS: D(pre) in responders group (RG) was
      significantly lower than nonresponders group (NRG) (1.029 +/- 0.033 vs. 1.184 +/-
      0.055, *10(-3) mm(2) /s, P = 0.020). ADC(day4) and DeltaD(day4) were the most
      useful parameters of the two diffusional models to distinguish RG from NRG,
      respectively (area under the curve, 0.761 vs. 0.895). DeltaD(day4) was more
      sensitive than ADC(day4) to predict treatment response to NAC (P = 0.006).
      CONCLUSION: Both DKI and monoexponential DWI showed potential to predict
      treatment response to NAC prior to morphological change. DKI may be superior to
      monoexponential DWI for predicting early response to NAC in patients with locally
      advanced NPC.

PMID- 25873207
TI  - Comparative diagnostic accuracy of magnetic resonance elastography vs. eight
      clinical prediction rules for non-invasive diagnosis of advanced fibrosis in
      biopsy-proven non-alcoholic fatty liver disease: a prospective study.
AB  - BACKGROUND: Two-dimensional magnetic resonance elastography (2D-MRE) is an
      advanced magnetic resonance method with high diagnostic accuracy for predicting
      advanced fibrosis in non-alcoholic fatty liver disease (NAFLD) patients. However,
      no prospective, head-to-head comparisons between 2D-MRE and clinical prediction
      rules (CPRs) have been performed in patients with biopsy-proven NAFLD. AIM: To
      compare the diagnostic utility of 2D-MRE against that of eight CPRs (AST:ALT
      ratio, APRI, BARD, FIB-4, NAFLD Fibrosis Score, Bonacini cirrhosis discriminant
      score, Lok Index and NASH CRN model) for predicting advanced fibrosis in a
      prospective cohort with paired liver biopsy as the gold standard. METHODS: This
      is a cross-sectional analysis of a prospective study of 102 patients (58.8%
      women) with biopsy-proven NAFLD, 2D-MRE and clinical research assessment within
      90 days of biopsy. Receiver operating characteristic (ROC) analysis was performed
      to assess the performance of 2D-MRE and CPRs for predicting advanced fibrosis.
      RESULTS: The mean (+/-s.d.) age and BMI were 51.3 (+/-14.0) years and 31.7 (+/
      5.5) kg/m(2) respectively. 48, 26, 9, 13 and 6 patients had stage 0, 1, 2, 3 and
      4 fibrosis respectively. The area under ROC curve (AUROC) was 0.957 for 2D-MRE
      and between 0.796 and 0.861 for the CPRs. FIB-4 was the best-performing CPR at
      predicting advanced fibrosis with AUROC of 0.861. In head-to-head comparisons
      using the DeLong test, 2D-MRE had significantly better AUROC (P < 0.05) than each
      CPR for predicting advanced fibrosis. CONCLUSION: Compared to clinical prediction
      rules, 2D-MRE provides significantly higher accuracy for the diagnosis of
      advanced fibrosis in NAFLD patients.

PMID- 25873209
TI  - Acylsulfonamide-Functionalized Zwitterionic Gold Nanoparticles for Enhanced
      Cellular Uptake at Tumor pH.
AB  - A nanoparticle design featuring pH-responsive alkoxyphenyl acylsulfonamide
      ligands is reported herein. As a result of ligand structure, this nanoparticle is
      neutral at pH 7.4, becoming positively charged at tumor pH (<6.5). The particle
      uptake and cytotoxicity increase over this pH range. This pH-controlled uptake
      and toxicity makes this particle a promising tool for tumor selective therapy. 

PMID- 25873211
TI  - New Look at BTEX: Are Ambient Levels a Problem?
AB  - Benzene, toluene, ethylbenzene, and xylene (BTEX) are retrieved during fossil
      fuel extraction and used as solvents in consumer and industrial products, as
      gasoline additives, and as intermediates in the synthesis of organic compounds
      for many consumer products. Emissions from the combustion of gasoline and diesel
      fuels are the largest contributors to atmospheric BTEX concentrations. However,
      levels indoors (where people spend greater than 83% of their time) can be many
      times greater than outdoors. In this review we identified epidemiological studies
      assessing the noncancer health impacts of ambient level BTEX exposure (i.e.,
      nonoccupational) and discussed how the health conditions may be hormonally
      mediated. Health effects significantly associated with ambient level exposure
      included sperm abnormalities, reduced fetal growth, cardiovascular disease,
      respiratory dysfunction, asthma, sensitization to common antigens, and more.
      Several hormones including estrogens, androgens, glucocorticoids, insulin, and
      serotonin may be involved in these health outcomes. This analysis suggests that
      all four chemicals may have endocrine disrupting properties at exposure levels
      below reference concentrations (i.e., safe levels) issued by the U.S.
      Environmental Protection Agency. These data should be considered when evaluating
      the use of BTEX in consumer and industrial products and indicates a need to
      change how chemicals present at low concentrations are assessed and regulated. 

PMID- 25873210
TI  - Two families with novel missense mutations in COL4A1: When diagnosis can be
      missed.
AB  - Mutations in COL4A1, encoding one of the six collagen type IV proteins, cover a
      wide spectrum of autosomal dominant overlapping phenotypes including
      porencephaly, small-vessel disease and hemorrhagic stroke, leukoencephalopathy,
      hereditary angiopathy with nephropathy, aneurysms and muscle cramp (HANAC)
      syndrome, and Walker-Warburg syndrome. Over 50 mutations are known, mainly being
      missense changes. Intra- and inter-familial variability has been reported. We
      studied two Italian families in which the proband had a clinical diagnosis of
      COL4A1-related disorder. We found two novel mutations (c.1249G>C; p.Gly417Arg and
      c.2662G>C; p.Gly888Arg). Both involved highly conserved amino acids and were
      predicted as being deleterious by bioinformatics tools. The c.1249G>C
      (p.Gly417Arg) segregated in four subjects with variable neurological phenotypes,
      namely leukoencephalopathy with muscle symptoms, brain small-vessel disease, and
      mild infantile encephalopathy. A fourth case was a carrier of the mutation
      without any neurological symptoms and an MRI with a specific white matter
      anomaly. The c.2662G>C (p.Gly888Arg) mutation was de novo in the proband. After a
      temporary motor impairment at age 14, the subject complained of mild imbalance at
      age 30, during the third trimester of her twin pregnancy, when an anomaly of the
      left brain hemisphere was documented in one fetus. Both her male dizygotic twins
      presented a severe motor delay, early convulsions, and leukoencephalopathy, and
      were carriers of the mutation. In summary, we confirm that high intra-familial
      variability of COL4A1 mutations with very mild phenotypes, the apparent
      incomplete penetrance, and de novo changes may become a "dilemma" for clinicians
      and genetic counselors.

PMID- 25873212
TI  - Linking extremely low birth weight and internalizing behaviors in adult
      survivors: Influences of neuroendocrine dysregulation.
AB  - Young adult survivors of extremely low birth weight (ELBW; <1000 g) are known to
      be at elevated risk for internalizing problems, though little is known about the
      mechanisms that may lead to higher levels of psychopathology in this vulnerable
      group. We examined the moderating influence of neuroendocrine functioning on the
      link between being born at ELBW and internalizing behaviors at age 30-35.
      Salivary cortisol was collected 20 min after completion of a social stress task
      in 83 ELBW adult survivors and 89 normal birth weight (NBW; >2500 g) controls.
      Using a median split, participants were separated into two groups (high or low
      afternoon cortisol levels). ELBW survivors with "high" afternoon cortisol levels
      self-reported significantly higher levels of internalizing behaviors compared to
      those with "low" afternoon cortisol levels. This association between afternoon
      cortisol and internalizing symptoms did not exist among NBW controls. These
      results are suggestive of a differential susceptibility for internalizing
      behaviors among ELBW survivors, depending on their ability to regulate
      neuroendocrine responses.

PMID- 25873214
TI  - Randomized Controlled Clinical Trial of All-Ceramic Single Tooth Implant
      Reconstructions Using Modified Zirconia Abutments: Radiographic and Prosthetic
      Results at 1 Year of Loading.
AB  - PURPOSE: This study aims to test whether or not veneering of the submucosal part
      of zirconia abutments with pink dental ceramic affects radiographic and technical
      outcomes of implant-supported single crowns (ISSC). MATERIALS AND METHODS: Single
      tooth implants were randomly restored with either pink-veneered zirconia
      abutments (test; n = 10) or non-veneered zirconia abutments (control group; n =
      10) and all-ceramic crowns. At baseline (crown insertion), and 6- and 12-month
      radiographic and technical evaluations were performed including standardized x
      rays and modified United States Public Health Service criteria (technical).
      Survival and complication rates were assessed for implants and restorations.
      Robust linear mixed model analysis was performed to investigate the effect of
      group and time-point on radiographic outcomes. RESULTS: At 1 year, the survival
      rate for implants was 100% and 95% for ISSC. Most of the implants were placed
      subcrestally. Therefore, mean marginal bone levels decreased in both groups
      between implant insertion and baseline (p < .05), but then remained stable up to
      1 year (test: 0.15 mm +/- 0.42 mm; control 0.23 mm +/- 0.63 mm) (p > .005). At 6
      months, one minor chipping occurred in the test group. At 1 year, three crowns
      (control) exhibited occlusal roughness. In addition, one abutment fracture
      occurred (test). The differences between test and control group were not
      statistically significantly different for any of the evaluated outcome measures
      (p > .05). CONCLUSIONS: Veneering of the submucosal part of zirconia abutments
      did not affect biological and technical outcomes of ISSCs. Technical
      complications of the reconstructions, however, were frequent, resulting in a rate
      of 75% of the crowns being complication free.

PMID- 25873213
TI  - Comparing different dosing regimens of bevacizumab in the treatment of
      neovascular macular degeneration: study protocol for a randomised controlled
      trial.
AB  - BACKGROUND: Bevacizumab (Avastin(r)) is as effective as ranibizumab (Lucentis(r))
      in the treatment of neovascular age-related macular degeneration (nAMD). However
      it has two important structural differences. First, it has two active sites
      instead of one; second, it retains the Fc portion of the antibody which would be
      expected to confer a significantly longer half-life. These agents have been
      associated with systemic complications including strokes, so it is desirable to
      use the smallest effective dose. Furthermore, the standard dosing regimen
      requires monthly hospital visits, which present a significant challenge both to
      the hospital services and to the patients (who are elderly). METHODS/DESIGN:
      Patients >=50 years who are eligible for anti-vascular endothelial growth factor
      (VEGF) treatment of nAMD in the NHS, who are either newly referred for treatment
      or have reactivation of nAMD and who have not received treatment to either eye
      for the previous six months. We have designed a factorial multi-centre masked
      randomised controlled trial using bevacizumab as the intervention, with patients
      randomised to one of four arms: to standard or low dose and to monthly or two
      monthly patient review. The aim is to recruit sufficient patients (around 1,000)
      to obtain 304 patients meeting the endpoint over a four-year period. The primary
      endpoint is time to treatment failure to be analysed using Cox regression.
      DISCUSSION: This randomised control trial will show if half dose and two monthly
      as required is as effective as full dose and monthly regimes. A two monthly as
      required regimen of Bevacizumab would significantly reduce both the cost and the
      service delivery burden for the treatment of nAMD while a reduced dose would be
      expected to enhance the safety profile of this treatment regime. TRIAL
      REGISTRATION: International Standard Randomised Controlled Trial Number:
      ISRCTN95654194 , registered on 22 September 2009.

PMID- 25873215
TI  - Anagrelide hydrochloride and ruxolitinib for treatment of polycythemia vera.
AB  - INTRODUCTION: New treatment options for polycythemia vera (PV) have recently
      become available. This article reviews current treatment strategies for PV with a
      focus on anagrelide and ruxolitinib. AREAS COVERED: The current treatment of PV
      is directed towards reducing the risk of additional thrombotic events. In
      addition to phlebotomy and aspirin, patients who are believed to have high-risk
      disease also receive cytoreductive therapy. Hydroxyurea (HU) and PEG-IFN are most
      commonly used first-line treatments. The use of anagrelide in PV is limited to
      situations where patient develops thrombohemorrhagic episodes in the setting of
      extreme thrombocytosis. The role of ruxolitinib in treatment of PV has not been
      fully established but based on a recently completed Phase III trial it will
      likely serve as a second-line option for patients with systemic symptoms. EXPERT
      OPINION: HU and PEG-IFN are frontline therapies for patients with high-risk PV.
      Anagrelide use should be restricted to patients with clinical consequences of
      extreme thrombocytosis. Ruxolitinib is a treatment option for patients who fail
      frontline therapies. However, long-term effects and toxicities are not yet fully
      known.

PMID- 25873217
TI  - [Fatal encephalitis caused by a parasite].
AB  - BACKGROUND: Encephalitis caused by a free-living amoeba is relatively rare and
      usually fatal. This is because the diagnosis is often made late and treatment is
      difficult. CASE DESCRIPTION: A 41-year-old patient with a previous history
      including kidney transplant was admitted with clinical symptoms of encephalitis.
      Brain imaging showed a number of hypodense regions, which were possibly
      abscesses. Although an infectious cause seemed probable, even the most extensive
      antimicrobial treatment was ineffective. The cause was not found until 2 months
      after the patient's death: infection with Balamuthia mandrillaris. A PCR test was
      used to detect this amoeba. CONCLUSION: This case study describes the first
      patient in the Netherlands to be diagnosed with granulomatous amoebic
      encephalitis caused by B. mandrillaris. An amoeba may be the cause of
      encephalitis with either a fulminant course or with a gradual increase of
      symptoms, without conventional anti-infective therapy being effective.

PMID- 25873216
TI  - Salicylate-induced changes in immediate-early genes in the hippocampal CA1 area.
AB  - Studies have suggested that salicylate affects neuronal function via interactions
      with specific membrane channels/receptors. However, the effect of salicylate on
      activity and synaptic morphology of the hippocampal Cornu Ammonis (CA) 1 area
      remains to be elucidated. The activation of immediate-early genes (IEGs) was
      reported to correlate with neuronal activity, in particular activity-regulated
      cytoskeleton-associated protein and early growth response gene 1. The aim of the
      present study was to evaluate the expression of these IEGs, as well that of N
      methyl D-aspartate (NMDA) receptor subunit 2B in rats following acute and chronic
      salicylate treatment. Protein and messenger RNA levels of all three genes were
      increased in rats following chronic administration of salicylate (300 mg/kg for
      10 days), returning to baseline levels 14 days post-cessation of treatment. The
      transient upregulation of gene expression following treatment was accompanied by
      ultrastructural alterations in hippocampal CA1 area synapses. An increase in
      synaptic interface curvature was observed as well as an increased number of
      presynaptic vesicles; in addition, postsynaptic densities thickened and
      lengthened. In conclusion, the results of the present study indicated that
      chronic exposure to salicylate may lead to structural alteration of hippocampal
      CA1 neurons, and it was suggested that this process occurs through induced
      expression of IEGs via NMDA receptor activation.

PMID- 25873218
TI  - [Spontaneous, atraumatic rupture of the spleen in a young man].
AB  - BACKGROUND: A spontaneous, atraumatic splenic rupture is a splenic rupture
      without a history of trauma. Rupture of this type may occur in a healthy patient
      but may also be seen in the context of an underlying neoplastic, haematological,
      infectious or local inflammatory condition. CASE DESCRIPTION: A 30-year-old man
      presented to the emergency department with acute pain in the left shoulder,
      thorax and upper abdomen, accompanied by signs of haemodynamic instability. No
      history of trauma was reported. Because the clinical symptoms could fit various
      abdominal and thoracic conditions, he was sent for a CT scan. This revealed a
      splenic rupture with haemoperitoneum. Emergency laparotomy and splenectomy were
      performed. Anamnestic, histopathological and other supplementary investigations
      revealed no indications of underlying pathology so that a diagnosis of
      "atraumatic idiopathic splenic rupture" was made. CONCLUSION: It is clinically
      difficult to diagnose a spontaneous, atraumatic rupture of the spleen due to the
      overlap in presentation with other, more common abdominal and thoracic
      conditions. A CT scan is essential to detect such a rupture promptly in order to
      provide appropriate surgical intervention.

PMID- 25873219
TI  - [Resumption of antithrombotic treatment after an intracerebral haemorrhage].
AB  - There is no evidence from randomised clinical trials with regard to the question
      if and when to resume antithrombotic medication in patients who have suffered an
      intracerebral haemorrhage and in whom medication continues to be indicated. It is
      unknown whether new oral anticoagulants are more suitable than vitamin K
      antagonists in this group of patients. Oral anticoagulants should probably not be
      resumed in patients with a lobar intracerebral haemorrhage caused by cerebral
      amyloid angiopathy. They can be considered in patients with a haemorrhage in
      subcortical regions of the brain, the brain stem or the cerebellum, provided that
      blood pressure levels are under control. Depending on the risk of a cardiac
      embolus, antithrombotic medication can be resumed from 1 to 10 weeks after the
      intracerebral haemorrhage. In patients with atrial fibrillation this risk can be
      calculated using the CHA2DS2-VASc score. In patients with a cardiac indication
      for antithrombotic medication the decision whether or not to resume medication
      should be made by a cardiologist and a neurologist in collaboration.

PMID- 25873220
TI  - [An infant with a suspicious lesion on her abdomen].
AB  - A six-month-old female girl presented with a lesion on her right hemi-abdomen.
      The lesion occurred after she visited her father, who just came out of prison.
      Therefore, child abuse was suspected. A skin culture showed Staphylococcus
      aureus. The diagnosis was 'impetigo vulgaris'. Treatment with local antibiotics
      was successful. 

PMID- 25873221
TI  - [The introduction of new medical devices].
AB  - Regulation of the introduction of new or improved medical devices is
      fundamentally different from that of new drugs and is inadequate in its current
      form. This was recently demonstrated by large-scale problems with medical devices
      in various specialist fields. Steps have been taken by scientific professional
      associations, regulating authorities and industry to prevent these problems from
      happening in the future. However, these steps have not yet been implemented or
      have not been sufficiently well implemented, and have not been completely
      coordinated. The practitioner therefore needs to remain extremely critical when
      using new medical devices. 

PMID- 25873222
TI  - [Diagnostic guideline and treatment of dementia].
AB  - - The Dutch dementia guideline has been extended to include recommendations in
      the area of psychosocial interventions for patients, caregivers and
      professionals.- The diagnostic recommendations in the revised directive are based
      on a stepwise work-up with the aim of establishing the cause of the dementia.
      This is guided by the recent diagnostic criteria, evidence of the diagnostic
      value of additional investigations, and the patient's wishes.- Although there
      have been no major breakthroughs in the treatment of patients with Alzheimer's
      disease in recent years, the revised guideline also contains important new
      recommendations in this area. For example, it includes recommendations on
      administration routes (first-choice use of patches or preparations with slow
      release of cholinesterase inhibitors), the use of combination therapy (not
      prescribing memantine in combination with cholinesterase inhibitors) and regular
      monitoring of the effectiveness of antipsychotics and cholinesterase inhibitors.-
      The guideline (in Dutch) can be found at www.richtlijnendatabase.nl (search for
      'dementie') and will be actively implemented. 

PMID- 25873223
TI  - [Overtreatment in couples with unexplained subfertility].
AB  - OBJECTIVE: To assess adherence to expectant management of 6-12 months in couples
      with unexplained subfertility, as recommended by the Dutch Networkguideline
      Subfertility. DESIGN: A retrospective cohort study in 25 clinics. METHOD: Couples
      were eligible to participate if they were diagnosed with unexplained subfertility
      and had a good prognosis of natural conception within one year (>30%), for these
      couples the network guideline recommends an expectant management. Outcomes
      measures are overtreatment, i.e. couples that started treatment within six
      months, and three quality indicators: 1) prognosis not calculated, 2) no correct
      expectant management advised, 3) starting treatment too soon despite a correct
      advise. Data collection was obtained from medical records. Multilevel regression
      analyses were performed to investigate associations of overtreatment with patient
      and clinic characteristics. RESULTS: We included 544 couples. Overtreatment
      occurred in 36% (N=198). In 34% (N=186) of all couples no prognosis was
      calculated (1), and in 42% (N=230) of all couples expectant management was not
      advised correctly (2). When a correct expectant management of six to twelve
      months was advised, 16% (N=51) started treatment too soon anyway. Overtreatment
      occurred more frequently in childless couples, a higher female age, and a longer
      duration of infertility. CONCLUSION: Our findings show that developing and
      publishing guideline recommendations on expectant management is not enough and
      that overtreatment still occurs frequently. To improve future care the next step
      is to evaluate a tailored implementation strategy to improve adherence to the
      recommendations on expectant management by the Dutch Networkguideline
      Subfertility.

PMID- 25873224
TI  - [Intensive care patients who want to die at home: how can we fulfil this last
      wish?].
AB  - OBJECTIVE: To make an inventory of the number of intensive care (ICU) patients
      per year in the Netherlands who have been discharged home to die, and the
      conditions under which this does or should take place. DESIGN: Descriptive,
      survey study. METHOD: A survey was conducted across all ICU departments in the
      Netherlands in the spring of 2012. They were approached in writing and requested
      to answer a few questions about the possibility of immediate discharge home for
      ICU patients with a short life expectancy and receiving palliative care. RESULTS:
      A total of 46 surveys (52%) was returned from the 89 ICUs approached. Of these,
      21 (46%) had discharged patients home at the request of the patient or their
      family so that the anticipated death could take place at home. Of the
      respondents, 39 (85%), supported discharge home for these patients, and 7 (15%)
      were opposed to it. These opinions were equally divided across all three ICU
      levels in the Netherlands. Higher-level ICUs had discharged patients home more
      often in comparison with lower-level ICUs (19%, 43% and 75% for levels 1, 2 and
      3, respectively). The preconditions for transfer can be subdivided into patient
      conditions, care conditions and general conditions. CONCLUSION: ICU patients do
      sometimes want to die at home. It does not happen every day, but the wish is
      often granted in the Netherlands. There are certain general and patient-related
      conditions that have to be fulfilled. This article suggests a national guideline
      that could provide support on this subject.

PMID- 25873225
TI  - [Anticoagulants after intracerebral haemorrhage in frail elderly].
AB  - Restarting anticoagulants in frail older patients who have had an intracerebral
      haemorrhage as an adverse reaction to anticoagulant therapy is a major dilemma,
      and one which is not specifically addressed in the state-of-the-art paper on
      restarting anticoagulants elsewhere in this issue. Frail older persons have the
      highest risk of recurrent bleeding, but, in theory, also have the most benefit
      from anticoagulants due to the high absolute risk for ischemic events in atrial
      fibrillation, which is the major indication. However, frail older persons are
      largely excluded from trials with anticoagulants, which makes it impossible to
      solve this dilemma in an evidence-based way. Therefore, we argue that sound
      decision making cannot only be based on neurological or cardiological expertise,
      as proposed by others, but should include an overall comprehensive geriatric
      assessment, and, most importantly, patients and caregivers should be included in
      shared goal setting and shared decision making. 

PMID- 25873226
TI  - [Updated Dementia guideline: reflections from primary care].
AB  - The updated Dementia guideline of the Dutch Geriatrics Society (NVKG) recommends
      additional testing (e.g. EEG, cerebrospinal fluid, CT/MRI or SPECT scans) only in
      cases of persisting significant diagnostic uncertainty. This more parsimonious
      use of tests appears to contrast with the current trend for specialist memory
      assessment services to favour full test batteries for all patients, and may be
      more efficient and less burdensome for patients. However, unlike the benchmark
      Dementia guideline of the Dutch College of General Practitioners (NHG), the NVKG
      guideline recommends treatment of Alzheimer's disease patients with
      cholinesterase inhibitors or memantine. Although meta-analyses yield significant
      beneficial treatment effects, in our opinion these are not clinically relevant
      and are mostly short-lived and counterbalanced by the burden of adverse effects.
      Nevertheless, the NVKG guideline also devotes considerable attention to
      psychosocial interventions that are valuable for the quality of life of both
      patients and their carers. 

PMID- 25873227
TI  - Molecular modeling of bioorganometallic compounds: thermodynamic properties of
      molybdocene-glutathione complexes and mechanism of Peptide hydrolysis.
AB  - The computational study of bioinorganic complexes between transition metals and
      flexible ligands is still challenging, given that, besides requiring extensive
      conformational searches, the treatment of metal-ligand bonds demands the
      application of quantum chemical methods. Herein, the adducts formed between
      molybdocene, which exhibits antitumor activity and reacts with thiol groups to
      give stable water-soluble complexes, and the tripeptide glutathione, which is a
      major source of biological thiols, are studied. Conformational searches are
      performed using the semiempirical PM6 method followed by geometry optimizations
      and single-point calculations using density functional theory methods. In
      addition, molecular dynamics simulations of the molybdocene-glutathione complex
      involved in the regioselective hydrolysis of the Cys-Gly linkage are performed in
      explicit solvent. The reactive process is also studied theoretically on cluster
      models of both the molybdocene-bound and the free peptide. 

PMID- 25873228
TI  - Nitrogen-doped carbon nanotubes with metal nanoparticles as counter electrode
      materials for dye-sensitized solar cells.
AB  - Nitrogen-doped carbon nanotubes decorated with Co and Ni metal nanoparticles were
      assessed as counter electrodes (CEs) of dye-sensitized solar cells (DSSCs). These
      composites show good electrocatalytic activity toward the counter electrode
      reduction reaction (I3(-)-> I(-)) in DSSCs. The resulting devices using these
      composites as CEs display photovoltaic performance as good as, or even better
      than Pt-based devices, indicating their potential for application in DSSCs. 

PMID- 25873229
TI  - Graphomotor skills in children with developmental coordination disorder (DCD):
      Handwriting and learning a new letter.
AB  - The aim of the present study was to analyze handwriting difficulties in children
      with developmental coordination disorder (DCD) and investigate the hypothesis
      that a deficit in procedural learning could help to explain them. The
      experimental set-up was designed to compare the performances of children with DCD
      with those of a non-DCD group on tasks that rely on motor learning in different
      ways, namely handwriting and learning a new letter. Ten children with DCD and 10
      non-DCD children, aged 8-10 years, were asked to perform handwriting tasks
      (letter/word/sentence; normal/fast), and a learning task (new letter) on a
      graphic tablet. The BHK concise assessment scale for children's handwriting was
      used to evaluate their handwriting quality. Results showed that both the
      handwriting and learning tasks differentiated between the groups. Furthermore,
      when speed or length constraints were added, handwriting was more impaired in
      children with DCD than in non-DCD children. Greater intra-individual variability
      was observed in the group of children with DCD, arguing in favor of a deficit in
      motor pattern stabilization. The results of this study could support both the
      hypothesis of a deficit in procedural learning and the hypothesis of neuromotor
      noise in DCD.

PMID- 25873230
TI  - Serological evaluation of possible exposure to Ljungan virus and related
      parechovirus in autoimmune (type 1) diabetes in children.
AB  - Exposure to Ljungan virus (LV) is implicated in the risk of autoimmune (type 1)
      diabetes but possible contribution by other parechoviruses is not ruled out. The
      aim was to compare children diagnosed with type 1 diabetes in 2005-2011 (n = 69)
      with healthy controls (n = 294), all from the Jamtland County in Sweden, using an
      exploratory suspension multiplex immunoassay for IgM and IgG against 26 peptides
      of LV, human parechoviruses (HPeV), Aichi virus and poliovirus in relation to a
      radiobinding assay (RBA) for antibodies against LV and InfluenzaA/H1N1pdm09.
      Islet autoantibodies and HLA-DQ genotypes were also determined. 1) All five LV
      peptide antibodies correlated to each other (P < 0.001) in the suspension
      multiplex IgM- and IgG-antibody assay; 2) The LV-VP1_31-60-IgG correlated with
      insulin autoantibodies alone (P = 0.007) and in combination with HLA-DQ8 overall
      (P = 0.022) as well as with HLA-DQ 8/8 and 8/X subjects (P = 0.013); 3) RBA
      detected LV antibodies correlated with young age at diagnosis (P < 0.001) and
      with insulin autoantibodies (P < 0.001) especially in young HLA-DQ8 subjects (P =
      0.004); 4) LV-peptide-VP1_31-60-IgG correlated to RBA LV antibodies (P = 0.009);
      5) HPeV3-peptide-IgM and -IgG showed inter-peptide correlations (P < 0.001) but
      only HPeV3-VP1_1-30-IgG (P < 0.001) and VP1_95-124-IgG (P = 0.009) were related
      to RBA LV antibodies without relation to insulin autoantibody positivity (P =
      0.072 and P = 0.486, respectively). Both exploratory suspension multiplex IgG to
      LV-peptide VP1_31-60 and RBA detected LV antibodies correlated with insulin
      autoantibodies and HLA-DQ8 suggesting possible role in type 1 diabetes. It
      remains to be determined if cross-reactivity or concomitant exposure to LV and
      HPeV3 contributes to the seroprevalence.

PMID- 25873231
TI  - Rapid prototyping-assisted maxillofacial reconstruction.
AB  - Rapid prototyping (RP) technologies have found many uses in dentistry, and
      especially oral and maxillofacial surgery, due to its ability to promote product
      development while at the same time reducing cost and depositing a part of any
      degree of complexity theoretically. This paper provides an overview of RP
      technologies for maxillofacial reconstruction covering both fundamentals and
      applications of the technologies. Key fundamentals of RP technologies involving
      the history, characteristics, and principles are reviewed. A number of RP
      applications to the main fields of oral and maxillofacial surgery, including
      restoration of maxillofacial deformities and defects, reduction of functional
      bone tissues, correction of dento-maxillofacial deformities, and fabrication of
      maxillofacial prostheses, are discussed. The most remarkable challenges for
      development of RP-assisted maxillofacial surgery and promising solutions are also
      elaborated. 

PMID- 25873232
TI  - Cavity ring-up spectroscopy for ultrafast sensing with optical microresonators.
AB  - Spectroscopy of whispering-gallery mode microresonators has become a powerful
      scientific tool, enabling the detection of single viruses, nanoparticles and even
      single molecules. Yet the demonstrated timescale of these schemes has been
      limited so far to milliseconds or more. Here we introduce a scheme that is orders
      of magnitude faster, capable of capturing complete spectral snapshots at
      nanosecond timescales-cavity ring-up spectroscopy. Based on sharply rising
      detuned probe pulses, cavity ring-up spectroscopy combines the sensitivity of
      heterodyne measurements with the highest-possible, transform-limited acquisition
      rate. As a demonstration, we capture spectra of microtoroid resonators at time
      intervals as short as 16 ns, directly monitoring submicrosecond dynamics of their
      optomechanical vibrations, thermorefractive response and Kerr nonlinearity.
      Cavity ring-up spectroscopy holds promise for the study of fast biological
      processes such as enzyme kinetics, protein folding and light harvesting, with
      applications in other fields such as cavity quantum electrodynamics and pulsed
      optomechanics. 

PMID- 25873233
TI  - Surgeon, staff, and patient radiation exposure in minimally invasive
      transforaminal lumbar interbody fusion: impact of 3D fluoroscopy-based navigation
      partially replacing conventional fluoroscopy: study protocol for a randomized
      controlled trial.
AB  - BACKGROUND: Some symptomatic degenerative conditions of the lumbar spine may be
      treated with spinal fusion if conservative treatment has failed. The minimally
      invasive technique of transforaminal lumbar interbody fusion (MIS TLIF) is
      increasingly used but has been found to generate increased radiation exposure to
      the patient and staff. Modern three-dimensional (3D) C-arm devices are capable of
      providing conventional two-dimensional fluoroscopic images (x-rays) as well as 3D
      image sets for intraoperative navigation. This study was designed to compare the
      radiation exposure between these two intraoperative imaging techniques in MIS
      TLIF procedures. METHODS: This study is a randomized controlled trial. Forty
      participants scheduled to undergo monosegmental MIS TLIF will be recruited and
      randomly allocated to one of two groups with respect to the applied
      intraoperative imaging technique: conventional fluoroscopy (FLUORO group) and 3D
      fluoroscopy-based navigation combined with conventional fluoroscopy (NAV group).
      Furthermore, patients scheduled to undergo bisegmental MIS TLIF during the
      recruitment period for monosegmental MIS TLIF will be assessed for eligibility
      and will be randomly assigned separately. The primary endpoint is the radiation
      exposure to the surgeon and is measured by dosimeter readings. Secondary
      endpoints are the radiation exposure to the assistant surgeon, scrub nurse,
      anesthetist, patient, and C-arm as well as radiation exposure in relation to the
      body mass index of the patient. DISCUSSION: Results of this randomized study will
      help to compare the radiation exposure to the operating staff and patient during
      MIS TLIF procedures using conventional fluoroscopy versus 3D fluoroscopy-based
      navigation combined with conventional fluoroscopy. Furthermore, recommendations
      regarding the appropriate use of the investigated intraoperative imaging
      techniques will be made to improve radiation protection and to reduce radiation
      exposure. TRIAL REGISTRATION: Registration number of the German Clinical Trials
      Register: DRKS00004514 . Registration date: 11 August 2012.

PMID- 25873234
TI  - Impact of metabolic disorders on the relation between overweight/obesity and
      incident myocardial infarction and ischaemic stroke in fertile women: a
      nationwide cohort study.
AB  - AIMS: Whether overweight is a risk factor for cardiovascular disease in the
      absence of metabolic disorders remains under debate and is largely unexamined in
      young women. We evaluated the risk of myocardial infarction and ischaemic stroke
      in fertile women conditional on time-dependent presence of metabolic disorders.
      MATERIALS AND METHODS: From nationwide registers we identified all normal weight
      (body mass index [BMI] >= 18.5 to <25 kg m(-2) and overweight (BMI >= 25 kg m(
      2)) Danish women giving birth from 2004 to 2009. Using multivariable Poisson
      regression models adjusted for age, calendar year and smoking, the risk of the
      composite outcome of myocardial infarction and ischaemic stroke was assessed with
      metabolic disorders (i.e. hypertensive conditions, abnormal glucose metabolism
      and/or dyslipidaemia) included as time-dependent variables. RESULTS: The
      population comprised 261,489 women with median age of 30.5 years (interquartile
      range = [27.3, 33.8]). Median follow-up was 5.6 years (interquartile range =
      [4.0, 6.8]). Compared with normal weight women without metabolic disorders (with
      an incidence rate [IR] of 17.0 [95% confidence interval {CI} = 14.5-20.0] events
      per 100,000 person-years), overweight women without metabolic disorders had no
      significantly increased risk, IR 22.6 (CI = 18.3-27.8), adjusted incidence rate
      ratio (IRR), 1.26 (CI = 0.97-1.65). For women with metabolic disorders, IR was
      30.2 (CI = 18.8-48.6) and adjusted IRR 1.77 (CI = 1.07-2.93) in normal weight,
      while IR was 87.1 (CI = 67.6-112.2) and IRR 4.24 (CI = 5 3.11-5.79) in
      overweight. CONCLUSIONS: The risk of myocardial infarction and ischaemic stroke
      was more strongly associated with the presence of metabolic disorders than with
      overweight per se in fertile women. Targeting prevention of metabolic disorders
      might be beneficial to reduce cardiovascular disease in overweight/obese young
      women.

PMID- 25873235
TI  - Synthesis of a tricyclic bisguanidine compound structurally related to saxitoxin
      and its identification in paralytic shellfish toxin-producing microorganisms.
AB  - We recently reported the chemical synthesis and identification of the genetically
      predicted biosynthetic intermediates of saxitoxin (STX), including a 2
      aminoimidazole-bearing monoguanidine compound (Int-C'2) in two paralytic
      shellfish toxin (PST)-producing microorganisms. In this study, we achieved the
      direct conversion of Int-C'2 into a tricyclic bisguanidine compound (called
      Cyclic-C'), which is structurally related to STX, through oxidative
      intramolecular guanidine transfer to 2-aminoimidazole catalyzed by Pd/C under
      basic conditions in air. By using HPLC-MS analysis, Cyclic-C' was also identified
      in the PST-producing microorganisms, suggesting that Cyclic-C' is either another
      biosynthetic intermediate or a shunt product of PSTs. In addition, a weak
      inhibitory activity of Cyclic-C' to the voltage-gated sodium channels was
      detected by using a cell-based assay. 

PMID- 25873236
TI  - The Effects of Naproxen on Chondrogenesis of Human Mesenchymal Stem Cells.
AB  - Currently, there are no established treatments to prevent, stop, or even retard
      the degeneration of articular cartilage in osteoarthritis (OA). Biological repair
      of the degenerating articular cartilage would be preferable to surgery. There is
      no benign site where autologous chondrocytes can be harvested and used as a cell
      source for cartilage repair, leaving mesenchymal stem cells (MSCs) as an
      attractive option. However, MSCs from OA patients have been shown to
      constitutively express collagen type X (COL-X), a marker of late-stage
      chondrocyte hypertrophy. We recently found that naproxen (Npx), but not other
      nonsteroidal anti-inflammatory drugs, can induce collagen type X alpha 1
      (COL10A1) gene expression in bone marrow-derived MSCs from healthy and OA donors.
      In this study, we determined the effect of Npx on COL10A1 expression and
      investigated the intracellular signaling pathways that mediate such effect in
      normal human MSCs during chondrogenesis. MSCs were cultured in standard
      chondrogenic differentiation media supplemented with or without Npx. Our results
      show that Npx can regulate chondrogenic differentiation by affecting the gene
      expression of both Indian hedgehog and parathyroid hormone/parathyroid hormone
      related protein signaling pathways in a time-dependent manner, suggesting a
      complex interaction of different signaling pathways during the process. 

PMID- 25873237
TI  - Next-generation sequencing propels environmental genomics to the front line of
      research.

PMID- 25873238
TI  - C-Type natriuretic peptide maintains domestic cat oocytes in meiotic arrest.
AB  - Recent studies have shown that C-type natriuretic peptide (CNP; encoded by the
      natriuretic peptide C (NPPC) gene) plays an essential role in maintaining meiotic
      arrest of mouse and porcine oocytes. However, whether CNP inhibits feline meiotic
      resumption is not known. In the present study we used a domestic cat model to
      explore the role played by CNP in feline oocyte meiotic resumption. We determined
      mRNA expression of genes encoding CNP and its cognate receptor natriuretic
      peptide receptor 2 (NPR2) in antral follicles. NPPC mRNA was primarily expressed
      in mural granulosa cells, whereas NPR2 mRNA was predominantly expressed in
      cumulus cells. Following in vitro culture for 24h, 100nM CNP increased cGMP
      levels, and maintained meiotic arrest of oocytes associated with cumulus cells.
      When the duration of in vitro culture increased from 24h to 36h, the ability of
      CNP to maintain meiotic arrest decreased, and this was accompanied by a decrease
      in the steady state levels of NPR2 mRNA in cumulus cells. In addition, CNP
      decreased the rate of degeneration of oocytes. These results indicate that CNP is
      required to maintain meiotic arrest and prevent degeneration in domestic cat
      oocytes.

PMID- 25873239
TI  - Feasibility and efficacy of dose-dense and dose-intense ABVD for high-risk
      patients with advanced Hodgkin lymphoma.

PMID- 25873240
TI  - Improving effectiveness of systematic conservation planning with density data.
AB  - Systematic conservation planning aims to design networks of protected areas that
      meet conservation goals across large landscapes. The optimal design of these
      conservation networks is most frequently based on the modeled habitat suitability
      or probability of occurrence of species, despite evidence that model predictions
      may not be highly correlated with species density. We hypothesized that
      conservation networks designed using species density distributions more
      efficiently conserve populations of all species considered than networks designed
      using probability of occurrence models. To test this hypothesis, we used the
      Zonation conservation prioritization algorithm to evaluate conservation network
      designs based on probability of occurrence versus density models for 26 land bird
      species in the U.S. Pacific Northwest. We assessed the efficacy of each
      conservation network based on predicted species densities and predicted species
      diversity. High-density model Zonation rankings protected more individuals per
      species when networks protected the highest priority 10-40% of the landscape.
      Compared with density-based models, the occurrence-based models protected more
      individuals in the lowest 50% priority areas of the landscape. The 2 approaches
      conserved species diversity in similar ways: predicted diversity was higher in
      higher priority locations in both conservation networks. We conclude that both
      density and probability of occurrence models can be useful for setting
      conservation priorities but that density-based models are best suited for
      identifying the highest priority areas. Developing methods to aggregate species
      count data from unrelated monitoring efforts and making these data widely
      available through ecoinformatics portals such as the Avian Knowledge Network will
      enable species count data to be more widely incorporated into systematic
      conservation planning efforts. 

PMID- 25873242
TI  - 3-Dimensional bioprinting makes its mark: new tissue and organ printing methods
      are yielding critical new tools for the laboratory and clinic.

PMID- 25873241
TI  - Quantification of taraxasterol in rat plasma by LC/MS/MS: application to a
      pharmacokinetic study.
AB  - Taraxasterol, a pentacyclic triterpene from Taraxacum officinale, is one of the
      main active constituents of the herb. This study developed and validated a highly
      selective and sensitive liquid chromatography/tandem mass spectrometry for the
      determination of taraxasterol in rat plasma over the range of 9.0-5000 ng/mL.
      Chromatographic separation was achieved on a C18 (4.6 * 50 mm, 5.0 um) column
      with methanol-isopropanol-water-formic acid (80:10:10:0.1, v/v/v/v) as mobile
      phase with an isocratic elution. The flow rate was 0.7 mL/min. After adding
      cucurbitacin IIa as an internal standard (IS), liquid-liquid extraction was used
      for sample preparation using ethyl acetate. The atmospheric pressure chemical
      ionization source was applied and operated in positive ion mode. Selected
      reaction monitoring mode was used for the quantification of transition ions m/z
      409.4 -> 137.1 for taraxasterol and m/z 503.4 -> 113.1 for IS. The mean
      recoveries of taraxasterol in rat plasma ranged from 85.3 to 87.2%. The matrix
      effects for taraxasterol were between 98.5 and 104.0%. Intra- and inter-day
      precision were both <11.8%, and the accuracy of the method ranged from -7.0 to
      12.9%. The method was successfully applied to a pharmacokinetic study of
      taraxasterol after oral administration of 7.75, 15.5 and 31.0 mg/kg in rats.

PMID- 25873244
TI  - The CPTAC Data Portal: A Resource for Cancer Proteomics Research.
AB  - The Clinical Proteomic Tumor Analysis Consortium (CPTAC), under the auspices of
      the National Cancer Institute's Office of Cancer Clinical Proteomics Research, is
      a comprehensive and coordinated effort to accelerate the understanding of the
      molecular basis of cancer through the application of proteomic technologies and
      workflows to clinical tumor samples with characterized genomic and transcript
      profiles. The consortium analyzes cancer biospecimens using mass spectrometry,
      identifying and quantifying the constituent proteins and characterizing each
      tumor sample's proteome. Mass spectrometry enables highly specific identification
      of proteins and their isoforms, accurate relative quantitation of protein
      abundance in contrasting biospecimens, and localization of post-translational
      protein modifications, such as phosphorylation, on a protein's sequence. The
      combination of proteomics, transcriptomics, and genomics data from the same
      clinical tumor samples provides an unprecedented opportunity for tumor
      proteogenomics. The CPTAC Data Portal is the centralized data repository for the
      dissemination of proteomic data collected by Proteome Characterization Centers
      (PCCs) in the consortium. The portal currently hosts 6.3 TB of data and includes
      proteomic investigations of breast, colorectal, and ovarian tumor tissues from
      The Cancer Genome Atlas (TCGA). The data collected by the consortium is made
      freely available to the public through the data portal. 

PMID- 25873245
TI  - Thermal degradation of sucralose: a combination of analytical methods to
      determine stability and chlorinated byproducts.
AB  - In the late years, much attention has been brought to the scientific community
      regarding the safety of sucralose and its industrial applications. Although it is
      the most used artificial sweetener in foods and pharmaceuticals, many questions
      still arise on its potential to form chlorinated byproducts in high temperatures,
      as demonstrated by several recent studies. In the present contribution, we use a
      combination of differential scanning calorimetry and thermogravimetric analysis
      coupled with infrared spectroscopy (DSC/TGA/IR), Hot-stage microscopy (HSM) and
      high-resolution mass spectrometry (HRMS) on samples submitted to water bath at
      mild temperatures to evaluate a broad spectrum of hazardous compounds formed in
      the degradation of this product. TGA/IR has revealed that there is effective
      decomposition in form of CO2 along with the formation of hydrogen chloride and
      other minor compounds. HSM results have provided accurate information, where the
      melting of the crystals was observed, followed by decomposition. Chlorinated
      derivatives, including polychlorinated aromatic hydrocarbons (PCAHs) were also
      confirmed by HRMS. These findings not only corroborate the suspected instability
      of sucralose to high temperatures, but also indicate that even exposed to mild
      conditions the formation of hazardous polychlorinated compounds is observed. 

PMID- 25873246
TI  - Reducing the porosity and reflection loss of silicon nanowires by a sticky tape.
AB  - Engineering the porosity of silicon nanowires (SiNWs) is of fundamental
      importance, and this work introduces a new method for doing so. Metal-assisted
      chemical etching (MACE) of heavily doped Si(100) creates mesoporous silicon
      nanowires (mp-SiNWs). mp-SiNWs are transferred from the MACE-treated wafer to a
      sticky tape, leaving residues composed of broken mp-SiNWs and a mesoporous Si
      layer on the wafer. Then the taped wafer is re-treated by MACE, without changing
      the etching conditions. The second MACE treatment generates mp-SiNWs that are
      less porous and longer than those generated by the first MACE treatment, which
      can be attributed to the difference in the surface topography at the beginning of
      the etching process. Less porous mp-SiNWs reduce optical scattering from the
      porous Si skeletons, and vertically protrude on the wafer without aggregation to
      facilitate optical trapping. Consequently, less porous mp-SiNWs effectively
      reduce ultraviolet-visible reflection loss. 

PMID- 25873247
TI  - The effects of interfacial potential on antimicrobial propensity of ZnO
      nanoparticle.
AB  - The work investigates the role of interfacial potential in defining antimicrobial
      propensity of ZnO nanoparticle (ZnONP) against different Gram positive and Gram
      negative bacteria. ZnONPs with positive and negative surface potential are tested
      against different bacteria with varying surface potentials, ranging -14.7 to 
      23.6 mV. Chemically synthesized ZnONPs with positive surface potential show very
      high antimicrobial propensity with minimum inhibitory concentration of 50 and 100
      MUg/mL for Gram negative and positive bacterium, respectively. On other hand,
      ZnONPs of the same size but with negative surface potential show insignificant
      antimicrobial propensity against the studied bacteria. Unlike the positively
      charged nanoparticles, neither Zn(2+) ion nor negatively charged ZnONP shows any
      significant inhibition in growth or morphology of the bacterium. Potential
      neutralization and colony forming unit studies together proved adverse effect of
      the resultant nano-bacterial interfacial potential on bacterial viability. Thus,
      ZnONP with positive surface potential upon interaction with negative surface
      potential of bacterial membrane enhances production of the reactive oxygen
      species and exerts mechanical stress on the membrane, resulting in the membrane
      depolarization. Our results show that the antimicrobial propensity of metal oxide
      nanoparticle mainly depends upon the interfacial potential, the potential
      resulting upon interaction of nanoparticle surface with bacterial membrane. 

PMID- 25873248
TI  - Fibromyalgia, milnacipran and experimental pain modulation: study protocol for a
      double blind randomized controlled trial.
AB  - BACKGROUND: The prevalence of fibromyalgia increases worldwide and is
      characterized by widespread and chronic pain. Treatment is difficult and includes
      both drug and non-drug approaches. Milnacipran, an antidepressant, is used for
      fibromyalgia, with a possible beneficial effect on central pain modulation. Our
      hypothesis is that the efficacy of milnacipran in fibromyalgia depends on the
      performance of pain inhibitory controls. METHODS/DESIGN: A randomized, double
      blind, clinical trial (NCT01747044) with two parallel groups, in 48 women with
      fibromyalgia, is planned in the Clinical Pharmacology Center, University
      Hospital, Clermont-Ferrand, France. Conditioned pain modulation (estimated with
      thermal stimuli using a numeric pain rating scale), the primary endpoint measure,
      is evaluated before and one month after treatment with milnacipran or placebo.
      Secondary outcome measures include the predictability of pain descending pathways
      performance for milnacipran efficacy, tolerance and cognitive function. Data
      analysis is performed using mixed models; the tests are two-sided, with a type I
      error set at alpha = 0.05. Not only will this trial allow estimation of the
      beneficial effect of milnacipran on pain and on descending pain pathways but it
      will also evaluate whether the performance of this modulatory system could be
      predictive of its efficacy in alleviating pain. DISCUSSION: This method would
      allow clinicians to take a pro-active attitude by performing a rapid
      psychophysical test before starting milnacipran treatment and would avoid
      unnecessary prescription while preventing therapeutic failure in patients who
      often face this recurrent problem. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT01747044 .

PMID- 25873249
TI  - Surgical techniques, open versus minimally invasive gastrectomy after
      chemotherapy (STOMACH trial): study protocol for a randomized controlled trial.
AB  - BACKGROUND: Laparoscopic surgery has been shown to provide important advantages
      in comparison with open procedures in the treatment of several malignant
      diseases, such as less perioperative blood loss and faster patient recovery. It
      also maintains similar results with regard to tumor resection margins and
      oncological long-term survival. In gastric cancer the role of laparoscopic
      surgery remains unclear. Current recommended treatment for gastric cancer
      consists of radical resection of the stomach, with a free margin of 5 to 6 cm
      from the tumor, combined with a lymphadenectomy. The extent of the
      lymphadenectomy is considered a marker for radicality of surgery and quality of
      care. Therefore, it is imperative that a novel surgical technique, such as
      minimally invasive total gastrectomy, should be non-inferior with regard to
      radicality of surgery and lymph node yield. METHODS/DESIGN: The Surgical
      Techniques, Open versus Minimally invasive gastrectomy After CHemotherapy
      (STOMACH) study is a randomized, clinical multicenter trial. All adult patients
      with primary carcinoma of the stomach, in which the tumor is considered
      surgically resectable (T1-3, N0-1, M0) after neo-adjuvant chemotherapy, are
      eligible for inclusion and randomization. The primary endpoint is quality of
      oncological resection, measured by radicality of surgery and number of retrieved
      lymph nodes. The pathologist is blinded towards patient allocation. Secondary
      outcomes include patient-reported outcomes measures (PROMs) regarding quality of
      life, postoperative complications and cost-effectiveness. Based on a non
      inferiority model for lymph node yield, with an average lymph node yield of 20, a
      non-inferiority margin of -4 and a 90% power to detect non-inferiority, a total
      of 168 patients are to be included. DISCUSSION: The STOMACH trial is a
      prospective, multicenter, parallel randomized study to define the optimal
      surgical strategy in patients with proximal or central gastric cancer after neo
      adjuvant therapy: the conventional 'open' approach or minimally invasive total
      gastrectomy. TRIAL REGISTRATION: This trial was registered on 28 April 2014 at
      Clinicaltrials.gov with the identifier NCT02130726 .

PMID- 25873250
TI  - Study protocol for two randomized controlled trials examining the effectiveness
      and safety of current weekend allied health services and a new stakeholder-driven
      model for acute medical/surgical patients versus no weekend allied health
      services.
AB  - BACKGROUND: Disinvestment from inefficient or ineffective health services is a
      growing priority for health care systems. Provision of allied health services
      over the weekend is now commonplace despite a relative paucity of evidence
      supporting their provision. The relatively high cost of providing this service
      combined with the paucity of evidence supporting its provision makes this a
      potential candidate for disinvestment so that resources consumed can be used in
      other areas. This study aims to determine the effectiveness, cost-effectiveness
      and safety of the current model of weekend allied health service and a new
      stakeholder-driven model of weekend allied health service delivery on acute
      medical and surgical wards compared to having no weekend allied health service.
      METHODS/DESIGN: Two stepped wedge, cluster randomised trials of weekend allied
      health services will be conducted in six acute medical/surgical wards across two
      public metropolitan hospitals in Melbourne (Australia). Wards have been chosen to
      participate by management teams at each hospital. The allied health services to
      be investigated will include physiotherapy, occupational therapy, speech therapy,
      dietetics, social work and allied health assistants. At baseline, all wards will
      be receiving weekend allied health services. Study 1 intervention will be the
      sequential disinvestment (roll-in) of the current weekend allied health service
      model from each participating ward in monthly intervals and study 2 will be the
      roll-out of a new stakeholder-driven model of weekend allied health service
      delivery. The order in which weekend allied health services will be rolled in and
      out amongst participating wards will be determined randomly. This trial will be
      conducted in each of the two participating hospitals at a different time
      interval. Primary outcomes will be length of stay, rate of unplanned hospital
      readmission within 28 days and rate of adverse events. Secondary outcomes will be
      number of complaints and compliments, staff absenteeism, and patient discharge
      destination, satisfaction, and functional independence at discharge. DISCUSSION:
      This is the world's first application of the recently described non-inferiority
      (roll-in) stepped wedge trial design, and the largest investigation of the
      effectiveness of weekend allied health services on acute medical surgical wards
      to date. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry.
      REGISTRATION NUMBER: ACTRN12613001231730 (first study) and ACTRN12613001361796
      (second study). Was this trial prospectively registered?: Yes. Date registered: 8
      November 2013 (first study), 12 December 2013 (second study). Anticipated
      completion: June 2015. Protocol version: 1. Role of trial sponsor: KP and DL are
      directly employed by one of the trial sponsors, their roles were: KP assisted
      with overall development of research design and assisted with overall project
      management; DL contributed to project management, administration and
      communications strategy.

PMID- 25873252
TI  - Silencing of the TPM1 gene induces radioresistance of glioma U251 cells.
AB  - The present study was designed to investigate the relationship between
      tropomyosin 1 (TPM1) and radioresistance in human U251 cells. Radioresistant U251
      (RR-U251) cells were established by repeated small irradiating injury. TPM1
      levels in the U251 and RR-U251 cells were inhibited by transfection with TPM1
      short hairpin RNA (shRNA) while overexpression was induced by treatment with
      pcDNA3.1-TPM1. The radiosensitivity of the U251 and RR-U251 cells and the plasmid
      transfected cells was evaluated by cell viability, migration and invasion assays.
      Cell apoptosis was also examined in vitro. The radiosensitivity of U251
      xenografts was observed by tumor growth curve after radiotherapy in an in vivo
      experiment. Western blotting and immunohistochemistry were used to detect the
      level of TPM1 in vivo. The expression of TPM1 was significantly decreased in the
      RR-U251 cells, which may be correlated with the radioresistance of the glioma
      U251 cells. In the TPM1-silenced RR-U251 and TPM1-silenced U251 cells, cell
      viability, migration and invasion ability were significantly increased, and the
      rate of cell apoptosis was decreased. Consistent with these results, in the TPM1
      overexpressing U251 and RR-U251 cells, cell viability, migration and invasion
      abilities were markedly decreased, and increased apoptosis was noted when
      compared to the control group. Tumor growth of the U251 xenografts was
      significantly inhibited following treatment with pcDNA3.1-TPM1 combined with
      radiotherapy. Taken together, these results indicate that TPM1 may be one
      mechanism underlying radiation resistance, and TPM1 may be a potential target for
      overcoming the radiation resistance in glioma.

PMID- 25873251
TI  - Silencing of uncoupling protein 2 by small interfering RNA aggravates
      mitochondrial dysfunction in cardiomyocytes under septic conditions.
AB  - Uncoupling protein 2 (UCP2) regulates the production of mitochondrial reactive
      oxygen species (ROS) and cellular energy transduction under physiological or
      pathological conditions. In this study, we aimed to determine whether
      mitochondrial UCP2 plays a protective role in cardiomyocytes under septic
      conditions. In order to mimic the septic condition, rat embryonic cardiomyoblast
      derived H9C2 cells were cultured in the presence of lipopolysaccharide (LPS) plus
      peptidoglycan G (PepG) and small interfering RNA (siRNA) against UCP2 (siUCP2)
      was used to suppress UCP2 expression. Reverse transcription quantitative
      polymerase chain reaction (RT-qPCR), western blot analysis, transmission electron
      microscopy (TEM), confocal microscopy and flow cytometry (FCM) were used to
      detect the mRNA levels, protein levels, mitochondrial morphology and
      mitochondrial membrane potential (MMP or DeltaPsim) in qualitative and
      quantitative analyses, respectively. Indicators of cell damage [lactate
      dehydrogenase (LDH), creatine kinase (CK), interleukin (IL)-6 and tumor necrosis
      factor (TNF)-alpha in the culture supernatant] and mitochondrial function [ROS,
      adenosine triphosphate (ATP) and mitochondrial DNA (mtDNA)] were detected. Sepsis
      enhanced the mRNA and protein expression of UCP2 in the H9C2 cells, damaged the
      mitochondrial ultrastructure, increased the forward scatter (FSC)/side scatter
      (SSC) ratio, increased the CK, LDH, TNF-alpha and IL-6 levels, and lead to the
      dissipation of MMP, as well as the overproduction of ROS; in addition, the
      induction of sepsis led to a decrease in ATP levels and the deletion of mtDNA.
      The silencing of UCP2 aggravated H9C2 cell damage and mitochondrial dysfunction.
      In conclusion, our data demonstrate that mitochondrial morphology and funtion are
      damaged in cardiomyocytes under septic conditions, while the silencing of UCP2
      using siRNA aggravated this process, indicating that UCP2 may play a protective
      role in cardiomyocytes under septic conditions.

PMID- 25873253
TI  - Practical communication guidance to improve phase 1 informed consent
      conversations and decision-making in pediatric oncology.
AB  - BACKGROUND: It can be difficult to explain pediatric phase 1 oncology trials to
      families of children with refractory cancer. Parents may misunderstand the
      information presented to them, and physicians may assume that certain topics are
      covered in the informed consent document and need not be discussed. Communication
      models can help to ensure effective discussions. METHODS: Suggestions for
      improving the informed consent process were first solicited from phase 1 study
      clinicians via questionnaire. Eight parents who had enrolled their child on a
      phase 1 pediatric oncology trial were recruited for an advisory group designed to
      assess the clinicians' suggestions and make additional recommendations for
      improving informed consent for pediatric phase 1 trials. RESULTS: A phase 1
      communication model was designed to incorporate the suggestions of clinicians and
      families. It focused on educating parents/families about phase 1 trials at
      specific time points during a child's illness, but specifically at the point of
      disease recurrence. An informative phase 1 fact sheet that can be distributed to
      families was also presented. CONCLUSIONS: Families who will be offered
      information regarding phase 1 clinical trials can first receive a standardized
      fact sheet explaining the general purpose of these early-phase clinical trials.
      Parental understanding may be enhanced further when oncologists address key
      themes, beginning at the time of diagnosis and continuing through important
      decision points during the child's illness. This model should be prospectively
      evaluated.

PMID- 25873254
TI  - Action seniors! - secondary falls prevention in community-dwelling senior
      fallers: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Falls are a 'geriatric giant' and are the third leading cause of
      chronic disability worldwide. About 30% of community-dwellers over the age of 65
      experience one or more falls every year leading to significant risk for
      hospitalization, institutionalization, and even death. As the proportion of older
      adults increases, falls will place an increasing demand and cost on the health
      care system. Exercise can effectively and efficiently reduce falls. Specifically,
      the Otago Exercise Program has demonstrated benefit and cost-effectiveness for
      the primary prevention of falls in four randomized trials of community-dwelling
      seniors. Although evidence is mounting, few studies have evaluated exercise for
      secondary falls prevention (that is, preventing falls among those with a
      significant history of falls). Hence, we propose a randomized controlled trial
      powered for falls that will, for the first time, assess the efficacy and
      efficiency of the Otago Exercise Program for secondary falls prevention.
      METHODS/DESIGN: A randomized controlled trial among 344 community-dwelling
      seniors aged 70 years and older who attend a falls prevention clinic to assess
      the efficacy and the cost-effectiveness of a 12-month Otago Exercise Program
      intervention as a secondary falls prevention strategy. Participants randomized to
      the control group will continue to behave as they did prior to study enrolment.
      The economic evaluation will examine the incremental costs and benefits generated
      by using the Otago Exercise Program intervention versus the control. DISCUSSION:
      The burden of falls is significant. The challenge is to make a difference - to
      discover effective, ideally cost-effective, interventions that prevent injurious
      falls that can be readily translated to the population. Our proposal is very
      practical - the exercise program requires minimal equipment, the physical
      therapist expertise is widely available, and seniors in Canada and elsewhere have
      adopted the program and complied with it. Our innovation includes applying the
      intervention to a targeted high-risk population, aiming to provide the best value
      for money. Given society's limited financial resources and the known and
      increasing burden of falls, there is an urgent need to test this feasible
      intervention which would be eminently ready for roll out. TRIAL REGISTRATION:
      ClinicalTrials.gov Protocol Registration System: NCT01029171; registered 7
      December 2009.

PMID- 25873255
TI  - Extended brief intervention to address alcohol misuse in people with mild to
      moderate intellectual disabilities living in the community (EBI-ID): study
      protocol for a randomised controlled trial.
AB  - BACKGROUND: There is some evidence that people with intellectual disabilities who
      live in the community are exposed to the same risks of alcohol use as the rest of
      the population. Various interventions have been evaluated in the general
      population to tackle hazardous or harmful drinking and alcohol dependence, but
      the literature evaluating interventions is very limited regarding intellectual
      disabilities. The National Institute for Health and Clinical Excellence
      recommends that brief and extended brief interventions be used to help young
      persons and adults who have screened as positive for hazardous and harmful
      drinking. The objective of this trial is to investigate the feasibility of
      adapting and delivering an extended brief intervention (EBI) to persons with
      mild/moderate intellectual disability who live in the community and whose level
      of drinking is harmful or hazardous. METHODS/DESIGN: The study has three stages,
      which include the adaptation of the Extended Brief Intervention (EBI) for people
      with intellectual disability, a single blind, randomised controlled trial of an
      individual Extended Brief Intervention to test the feasibility of the
      intervention, and a qualitative study that will assess the perceived
      acceptability and usefulness of the intervention. Fifty participants in total
      will be recruited from community intellectual disability services and social care
      or third sector organisations. The main outcome is a reduction in alcohol
      consumption measured by the Alcohol Use Disorders Identification Test.
      DISCUSSION: Alcohol misuse is a relatively under-researched mental health problem
      in people with intellectual disabilities. Therefore, the study addresses both
      diagnostic issues and the delivery of a simple first stage intervention, which is
      available to the population of average intelligence and young persons in
      particular. The findings from the study will guide the preparation of a large
      scale study to test whether this treatment is clinically and cost-effective in
      this population. TRIAL REGISTRATION: ISRCTN58783633 (19 December 2013).

PMID- 25873256
TI  - Identification of Azole Resistance Markers in Clinical Isolates of Candida
      tropicalis Using cDNA-AFLP Method.
AB  - BACKGROUND: Global reports have highlighted the increasing prevalence of Candida
      tropicalis infections as well as organism(') s drug resistance. This study aimed
      at identifying azole resistance markers in clinical isolates of C. tropicalis,
      which will be a great resource for developing new drugs. METHODS: Two susceptible
      and resistant isolates of C. tropicalis were recovered from an epidemiological
      investigation of candidiasis in immunocompromised patients. C. tropicalis ATCC
      750 was used as reference strain. Antifungal susceptibility to fluconazole and
      itraconazole was determined using Clinical and Laboratory Standards Institute
      (CLSI) method. Complementary DNA-amplified fragment length polymorphism (cDNA
      AFLP) technology and real-time reverse-transcriptase (RT) PCR were used for
      identification of potential genes involved in azole resistance of C. tropicalis
      clinical isolates. RESULTS: Five genes encoding the following enzymes were
      identified as superoxide dismutase (SOD) implicated in antioxidant defense,
      ornithine aminotransferase (OAT), acetyl ornithine aminotransferase (ACOAT),
      adenosylmethionine-8-amino-7-oxononanoate aminotransferase (DAPA AT), and 4
      aminobutyrate aminotransferase (ABAT)-belonging to pyridoxal phosphate (PLP)
      dependent enzymes and acting in an important physiological role in many fungal
      cell cycles. Real-time RT-PCR confirmed mRNA level of the aforementioned genes.
      CONCLUSION: Our findings showed that factors such as PLP-dependent enzymes and
      SOD might be implicated in drug resistance in C. tropicalis clinical isolate.
      Therefore, further studies are required to explore the accurate biological
      functions of the mentioned genes that would be helpful for effective drug
      development.

PMID- 25873257
TI  - Antihyperlipidemic bioactivity of Alpinia officinarum (Hance) Farw Zingiberaceae
      can be attributed to the coexistance of curcumin, polyphenolics, dietary fibers
      and phytosterols.
AB  - Rhizoma A. officinarum (Hance) Farw, synonymously is called rhizoma galangae or
      smaller galangal (hereafter abbreviated as AO). Numerous studies reported that AO
      possesses anti-inflammatory, anticancer, chemoprotective, antibacterial,
      antifungal and diuretic properties. To understand whether AO exhibits
      antihyperlipidemic bioactivity and what is the mechanism of action, we performed
      chemical and animal studies using hamsters (age: 4 weeks, body weight: 45 +/- 4
      g). The grouping of the animals was as follows: control, high fat (HF) diet, HF +
      AO2%, HF + AO4%, HF + AO6%, HF + AO8% and HF + AO10%. AO contained curcumin 5.67
      mg g(-1) (on wet basis), crude fiber 1.3% +/- 0.0%, soluble diet fiber 92 +/- 2
      mg g(-1), insoluble diet fiber 502 +/- 5 mg g(-1), and phytosterols 63.9 +/- 1.6
      mg/100 g. Its methanolic extract consisted of high polyphenolics 4927.8 +/- 101.1
      mgGAE/100 g and flavonoids 593.2 +/- 22.2 mgQE/100 g. The enlarged organs,
      including liver, kidney, and spleen, which were elicited by HF were completely
      alleviated by AO supplement diets. Levels of serum cholesterol, triglyceride, LDL
      C, HDL-C and LDL-C/HDL-C ratio for the control originally were 138 +/- 6, 98 +/-
      4, 40 +/- 5, 168 +/- 7 mg dL(-1) and 0.24, which were elevated by HF to 319 +/-
      12, 223 +/- 13, 108 +/- 11, 194 +/- 6 mg dL(-1) and 0.05, and alleviated
      completely by HF + AO8% and HF + AO10%. In vitro, AO extracts showed potent DPPH
      free radical-scavenging and superoxide anion scavenging capabilities. In vivo, AO
      (at dose >=8%) dose-dependently alleviated levels of superoxide dismutase,
      catalase, GSH, and MDA to 117 +/- 6.9 U mL(-1), 32.9 +/- 3.7 U mL(-1), 7.0 +/-
      1.7 MUmol mL(-1) and 1.8 +/- 0.4 nmol L(-1), respectively, exhibiting the
      remarkable antioxidative and antihyperlipidemic effects of AO. Conclusively, we
      are the first to report the occurrence of curcumin in rhizoma A. officinarum.
      Curcumin synergistically elicits promising anti-dyslipidemic bioactivity with
      coexisting total polyphenolics, dietary fibers and phytosterols. 

PMID- 25873259
TI  - How I use health apps.

PMID- 25873258
TI  - Reproductive character displacement shapes a spatially structured petal color
      polymorphism in Leavenworthia stylosa.
AB  - Character displacement is a potentially important process driving trait evolution
      and species diversification. Floral traits may experience character displacement
      in response to pollinator-mediated competition (ecological character
      displacement) or the risk of forming hybrids with reduced fitness (reproductive
      character displacement). We test these and alternative hypotheses to explain a
      yellow-white petal color polymorphism in Leavenworthia stylosa, where yellow
      morphs are spatially associated with a white-petaled congener (Leavenworthia
      exigua) that produces hybrids with complete pollen sterility. A reciprocal
      transplant experiment found limited evidence of local adaptation of yellow color
      morphs via increased survival and seed set. Pollinator observations revealed that
      Leavenworthia attract various pollinators that generally favor white petals and
      exhibit color constancy. Pollen limitation experiments showed that yellow petals
      do not alleviate competition for pollination. Interspecific pollinator movements
      were infrequent and low hybridization rates (~0.40-0.85%) were found in each
      morph, with natural rates likely being lower. Regardless, hybridization rates
      were significantly higher in white morphs of L. stylosa, yielding a small
      selection coefficient of s = 0.0042 against this phenotype in sympatry with L.
      exigua. These results provide support for RCD as a mechanism contributing to the
      pattern of petal color polymorphism in L. stylosa.

PMID- 25873261
TI  - A cosolvency effect on tunable thermosensitive core-shell nanoparticle gels.
AB  - The influence of co-solvents on the swelling behavior of tunable thermosensitive
      core-shell nanoparticle gels was investigated. The poly(methyl methacrylate)
      (PMMA) core and poly(2-hydroxyethyl methacrylate) (PHEMA) shell network in 1
      propanol reacted differently upon the addition of three co-solvents (cyclohexane
      (CHX), 1,3-propanediol (PDO), and water), resulting in highly controllable
      swelling properties of the core-shell gels. In particular, a strongly enhanced
      solvation effect, called the cosolvency phenomenon, occurred even with a very
      small amount of water (1-3 wt%). To examine the tunability, thermo-optical
      analysis (TOA) and photon correlation spectroscopy (PCS) were employed. The
      results show that a small addition of CHX, PDO, or water induced the
      "lower/upper," "even/upper," and "lower/lower" volume transition temperatures
      (VTTs) of the core-shell networks, respectively. For theoretical treatment, a
      multi-component lattice theory of mixing was combined with the Flory-Rehner (F-R)
      chain model to calculate the net free energy of mixing. The required interaction
      parameters were obtained from the binary and ternary phase diagrams of the linear
      polymer solutions and were applied directly to the swelling calculation of the
      cross-linked core-shell network solutions. The calculated results corresponded
      well with the experimental swelling data without further adjustment. 

PMID- 25873260
TI  - Divergent expression of alpha-ENaC in middle ear mucosa in the course of otitis
      media with effusion induced by barotrauma.
AB  - CONCLUSION: Gene transcription and protein expression of alpha-ENaC showed a
      divergent expression in association with the development of OME induced by
      barotrauma. OBJECTIVES: ENaC was identified to mediate the fluid absorption
      through epithelia of the middle ear. This study was designed to investigate the
      involvement of ENaC in otitis media with effusion (OME) induced by barotrauma.
      METHODS: A rat model of otitis media with effusion was established using a
      pressure cabin. The dynamic expression of alpha-ENaC was detected by Real time
      PCR and western blot in the course of otitis media. RESULTS: Compared with the
      control, the volume of alpha-ENaC mRNA and protein increased significantly by
      3.18-fold and 2.8-fold on the 3(rd) day, respectively, while decreased by 0.54
      fold and 0.32-fold on the 7(th) day, respectively.

PMID- 25873262
TI  - Field-amplified sample injection in capillary electrophoresis with amperometric
      detection for the ultratrace analysis of diastereomeric ephedrine alkaloids.
AB  - A coupling method of field-amplified sample injection (FASI) CE with amperometric
      detection is developed for ultratrace analysis of ephedrine alkaloids
      stereoisomers. FASI was introduced by injecting electrokinetically the sample
      solution for 10 s into the capillary filled with highly conductive background
      electrolyte (BGE). The diastereomeric selectivity and the detection sensitivity
      were improved by using borate buffer of high ionic strength as BGE. Parameters
      affecting FASI and CE separation were investigated to achieve the optimal
      conditions. Four analytes were separated within 15 min using 200 mmol/L borate
      buffer (pH 9.5) and separation voltage of +18 kV, with detection potential at
      +1.0 V (vs. Ag/AgCl) and carbon disc electrode as working electrode. Excellent
      linearity was observed between peak current and concentration of analytes in the
      range of 0.1-100 ng/mL. The LODs (S/N = 3) for (-)-ephedrine, (+)
      pseudoephedrine, (-)-N-methylephedrine and (+)-N-methylpseudoephedrine were 39.3,
      54.9, 30.8, and 44.1 pg/mL, respectively. The proposed method was successfully
      applied to the determination of alkaloids in Ephedra sinica, with results agreed
      well with HPLC method. Mean recoveries of 102.1-109.7% and RSDs less than 6% were
      found. And the merits of high sensitivity and selectivity, as well as a simple
      and stable operation, have been demonstrated. 

PMID- 25873263
TI  - Bioresponsive probes for molecular imaging: concepts and in vivo applications.
AB  - Molecular imaging is a powerful tool to visualize and characterize biological
      processes at the cellular and molecular level in vivo. In most molecular imaging
      approaches, probes are used to bind to disease-specific biomarkers highlighting
      disease target sites. In recent years, a new subset of molecular imaging probes,
      known as bioresponsive molecular probes, has been developed. These probes
      generally benefit from signal enhancement at the site of interaction with its
      target. There are mainly two classes of bioresponsive imaging probes. The first
      class consists of probes that show direct activation of the imaging label (from
      "off" to "on" state) and have been applied in optical imaging and magnetic
      resonance imaging (MRI). The other class consists of probes that show specific
      retention of the imaging label at the site of target interaction and these probes
      have found application in all different imaging modalities, including
      photoacoustic imaging and nuclear imaging. In this review, we present a
      comprehensive overview of bioresponsive imaging probes in order to discuss the
      various molecular imaging strategies. The focus of the present article is the
      rationale behind the design of bioresponsive molecular imaging probes and their
      potential in vivo application for the detection of endogenous molecular targets
      in pathologies such as cancer and cardiovascular disease.

PMID- 25873264
TI  - Metallophthalocyanine-based conjugated microporous polymers as highly efficient
      photosensitizers for singlet oxygen generation.
AB  - Singlet oxygen ((1) O2 ) is of great interest because of its potential
      applications in photodynamic therapy, photooxidation of toxic molecules, and
      photochemical synthesis. Herein, we report novel metallophthalocyanine (MPc)
      based conjugated microporous polymers (MPc-CMPs) as photosensitizers for the
      generation of (1) O2 . The rigid microporous structure efficiently improves the
      exposure of the majority of the MPc units to oxygen. The MPc-CMPs also exhibit an
      enhanced light-harvesting capability in the far-red region through their extended
      pi-conjugation systems. Their microporous structure and excellent absorption
      capability for long-wavelength photons result in the MPc-CMPs showing high
      efficiency for (1) O2 generation upon irradiation with 700 nm light, as evident
      by using 1,3-diphenylisobenzofuran as an (1) O2 trap. These results indicate that
      MPc-CMPs can be considered as promising photosensitizers for the generation of
      (1) O2 . 

PMID- 25873265
TI  - Leukocyte Cell-Derived Chemotaxin 2-Associated Amyloidosis: A Recently Recognized
      Disease with Distinct Clinicopathologic Characteristics.
AB  - Amyloidosis derived from leukocyte cell-derived chemotaxin 2 is a recently
      recognized form of amyloidosis, and it has already been established as a frequent
      form of systemic amyloidosis in the United States, with predominant involvement
      of kidney and liver. The disease has a strong ethnic bias, affecting mainly
      Hispanics (particularly Mexicans). Additional ethnic groups prone to develop
      amyloidosis derived from leukocyte cell-derived chemotaxin 2 include Punjabis,
      First Nations people in British Columbia, and Native Americans. Most patients are
      elderly who present with chronic renal insufficiency and bland urinary sediment.
      Proteinuria is variable, being absent altogether in about one third of patients.
      Liver involvement is frequently an incidental finding. Amyloidosis derived from
      leukocyte cell-derived chemotaxin 2 deposits shows a characteristic distribution:
      in the kidney, there is consistent involvement of cortical interstitium, whereas
      in the liver, there is a preferential involvement of periportal and pericentral
      vein regions. Concurrent renal disease is frequent, with diabetic nephropathy and
      IgA nephropathy being the most common. Patient survival is excellent, likely
      because of the rarity of cardiac involvement, whereas renal survival is guarded,
      with a median renal survival of 62 months in those without concurrent renal
      disease. There is currently no efficacious therapy for amyloidosis derived from
      leukocyte cell-derived chemotaxin 2 amyloidosis. Renal transplantation seems to
      be a reasonable treatment for patients with advanced renal failure, although the
      disease may recur in the allograft. The pathogenesis of amyloidosis derived from
      leukocyte cell-derived chemotaxin 2 amyloidosis has not yet been elucidated. It
      could be a result of leukocyte cell-derived chemotaxin 2 overexpression by
      hepatocytes either constitutively (controlled by yet-uncharacterized genetic
      defects) or secondary to hepatocellular damage. It is critical not to misdiagnose
      amyloidosis derived from leukocyte cell-derived chemotaxin 2 amyloidosis as Ig
      light chain-derived amyloidosis to avoid harmful chemotherapy. 

PMID- 25873266
TI  - The Ethics of Chronic Dialysis for the Older Patient: Time to Reevaluate the
      Norms.
AB  - Recent research highlights the potential burdens of hemodialysis for older
      patients with significant comorbidities, for whom there is clinical equipoise
      regarding the net benefits. With the advent of accountable care and bundled
      payment, previous incentives to offer hemodialysis to as many patients as
      possible are being replaced with a disincentive to dialyze high-risk patients.
      While this may offset the harm of overtreatment for some elderly patients, some
      voice concerns that the pendulum will swing too far back, with a return to ageist
      rationing of hemodialysis. Nephrologists should ensure that the patient's rights
      to be informed about the potential benefits and burdens of hemodialysis are
      respected, particularly because age, functional status, nutritional status, and
      comorbidities affect the net balance between benefits and burdens. Nephrologists
      are also called on to help patients make a decision, for which the patient's
      goals of care guide determination of potential benefit from hemodialysis. This
      article addresses concerns about present overtreatment and future risk of
      undertreatment of older adults with ESRD. It also discusses ways in which
      providers can ethically approach the question of initiation of hemodialysis in
      the elderly patient by including patient-specific estimates of prognosis, shared
      decision-making, and the use of specialist palliative care clinicians or ethics
      consultants for complex cases. 

PMID- 25873268
TI  - Chemically and electrochemically induced expansion and contraction of a ferrocene
      rotor.
AB  - A 2,2'-bipyridine-appended ferrocene rotor, 1,1'-di(5-yl-ethynyl-2,2'
      bipyridine)ferrocene, can be switched from a folded/stacked (syn) conformation to
      an extended/unstacked (anti) conformation by the addition of [Cu(CH3CN)4](PF6)
      and 6,6'-dimesityl-2,2'-bipyridine. This extension and contraction process was
      completely reversible and could be triggered either chemically or
      electrochemically. 

PMID- 25873267
TI  - Effect of Cinacalcet and Vitamin D Analogs on Fibroblast Growth Factor-23 during
      the Treatment of Secondary Hyperparathyroidism.
AB  - BACKGROUND AND OBJECTIVES: Cinacalcet and vitamin D are often combined to treat
      secondary hyperparathyroidism (SHPT) in patients on dialysis. Independent effects
      on fibroblast growth factor-23 (FGF-23) concentrations in patients on
      hemodialysis administered cinacalcet or vitamin D analogs as monotherapies during
      treatment of SHPT are evaluated. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A
      multicenter, randomized, open-label study to compare the efficacy of cinacalcet
      versus traditional vitamin D therapy for management of secondary
      hyperparathyroidism among subjects undergoing hemodialysis (PARADIGM) was a
      prospective, phase 4, multicenter, randomized, open-label study conducted
      globally. Participants (n=312) were randomized 1:1 to cinacalcet (n=155) or
      vitamin D analog (n=157) for 52 weeks. Levels of FGF-23 were measured at baseline
      and weeks 20 and 52. The absolute and percentage changes from baseline in plasma
      FGF-23, parathyroid hormone (PTH), calcium (Ca), phosphorus (P), and calcium
      phosphorus product (Ca*P) were assessed. Correlations and logistic regression
      were used to explore relationships between changes in FGF-23 and changes in PTH,
      Ca, P, and Ca*P from baseline to week 52 by treatment arm. RESULTS: Median
      (quartiles 1, 3) decrease in FGF-23 concentrations was observed in the cinacalcet
      arm (-40%; -63%, 16%) compared with median increase in the vitamin D analog arm
      (47%; 0%, 132%) at week 52 (P<0.001). Changes in FGF-23 in both arms were
      unrelated to changes in PTH (cinacalcet: r=0.17, P=0.11; vitamin D analog: r=
      0.04, P=0.70). Changes in FGF-23 in the vitamin D analog but not the cinacalcet
      arm were correlated with changes in Ca (cinacalcet: r=0.11, P=0.30; vitamin D
      analog: r=0.32, P<0.01) and P (cinacalcet: r=0.19, P=0.07; vitamin D analog:
      r=0.49, P<0.001). Changes in FGF-23 were correlated with changes in Ca*P in both
      arms (cinacalcet: r=0.26, P=0.01; vitamin D analog: r=0.57, P<0.001). Independent
      of treatment arm, participants with reductions in P or Ca*P were significantly
      more likely to show reductions in FGF-23. CONCLUSIONS: During treatment of SHPT,
      cinacalcet use was associated with a decrease in FGF-23 concentrations, whereas
      vitamin D analogs were associated with an increase. The divergent effects of
      these treatments on FGF-23 seem to be independent of modification of PTH. It is
      possible that effects of cinacalcet and vitamin D analogs on FGF-23 may be
      mediated indirectly by other effects on bone and mineral metabolism.

PMID- 25873270
TI  - Effects of prenatal stress on anxiety-like behavior and nociceptive response in
      rats.
AB  - We assess the anxiety-like behavior in the open field and elevated plus maze
      tests and measure the nociceptive response in the tail flick test following
      prenatal stress exposure in adult male and female Wistar rats. In both behavioral
      anxiety tests, prenatal stress increased the anxiety-like behavior in male PS
      rats, but not in females suggesting a strong sex-dependent anxiogenic effect. The
      tail flick results showed a hypersensitivity to pain in male and female PS rats
      with a subtle gender difference. These findings suggest that prenatal stress is
      an important risk factor for multiple mental disorders. 

PMID- 25873269
TI  - Concise Review: Targeting Cancer Stem Cells Using Immunologic Approaches.
AB  - Cancer stem cells (CSCs) represent a small subset of tumor cells which have the
      ability to self-renew and generate the diverse cells that comprise the tumor
      bulk. They are responsible for local tumor recurrence and distant metastasis.
      However, they are resistant to conventional radiotherapy and chemotherapy. Novel
      immunotherapeutic strategies that specifically target CSCs may improve the
      efficacy of cancer therapy. To immunologically target CSC phenotypes, innate
      immune responses to CSCs have been reported using Natural killer cells and
      gammadelta T cells. To target CSC specifically, in vitro CSC-primed T cells have
      been successfully generated and shown targeting of CSCs in vivo after adoptive
      transfer. Recently, CSC-based dendritic cell vaccine has demonstrated significant
      induction of anti-CSC immunity both in vivo in immunocompetent hosts and in vitro
      as evident by CSC reactivity of CSC vaccine-primed antibodies and T cells. In
      addition, identification of specific antigens or genetic alterations in CSCs may
      provide more specific targets for immunotherapy. ALDH, CD44, CD133, and HER2 have
      served as markers to isolate CSCs from a number of tumor types in animal models
      and human tumors. They might serve as useful targets for CSC immunotherapy.
      Finally, since CSCs are regulated by interactions with the CSC niche, these
      interactions may serve as additional targets for CSC immunotherapy. Targeting the
      tumor microenvironment, such as interrupting the immune cell, for example,
      myeloid-derived suppressor cells, and cytokines, for example, IL-6 and IL-8, as
      well as the immune checkpoint (PD1/PDL1, etc.) may provide additional novel
      strategies to enhance the immunological targeting of CSCs.

PMID- 25873271
TI  - Phenotype consequences of myophosphorylase dysfunction: insights from the McArdle
      mouse model.
AB  - KEY POINTS: This is the first study to analyse the effect of muscle glycogen
      phosphorylase depletion in metabolically different muscle types. In McArdle mice,
      muscle glycogen phosphorylase is absent in both oxidative and glycolytic muscles.
      In McArdle mice, the glycogen debranching enzyme (catabolic) is increased in
      oxidative muscles, whereas the glycogen branching enzyme (anabolic) is increased
      in glycolytic muscles. In McArdle mice, total glycogen synthase is decreased in
      both oxidative and glycolytic muscles, whereas the phosphorylated inactive form
      of the enzyme is increased in both oxidative and glycolytic enzymes. In McArdle
      mice, glycogen content is higher in glycolytic muscles than in oxidative muscles.
      Additionally, in all muscles analysed, the glycogen content is higher in males
      than in females. The maximal endurance capacity of the McArdle mice is
      significantly lower compared to heterozygous and wild-type mice. ABSTRACT:
      McArdle disease, caused by inherited deficiency of the enzyme muscle glycogen
      phosphorylase (GP-MM), is arguably the paradigm of exercise intolerance. The
      recent knock-in (p.R50X/p.R50X) mouse disease model allows an investigation of
      the phenotypic consequences of muscle glycogen unavailability and the
      physiopathology of exercise intolerance. We analysed, in 2-month-old mice [wild
      type (wt/wt), heterozygous (p.R50X/wt) and p.R50X/p.R50X)], maximal endurance
      exercise capacity and the molecular consequences of an absence of GP-MM in the
      main glycogen metabolism regulatory enzymes: glycogen synthase, glycogen
      branching enzyme and glycogen debranching enzyme, as well as glycogen content in
      slow-twitch (soleus), intermediate (gastrocnemius) and glycolytic/fast-twitch
      (extensor digitorum longus; EDL) muscles. Compared with wt/wt, exercise capacity
      (measured in a treadmill test) was impaired in p.R50X/p.R50X (~48%) and p.R50X/wt
      mice (~18%). p.R50X/p.R50X mice showed an absence of GP-MM in the three muscles.
      GP-MM was reduced in p.R50X/wt mice, especially in the soleus, suggesting that
      the function of 'slow-twitch' muscles is less dependent on glycogen catabolism.
      p.R50X/p.R50X mice showed increased glycogen debranching enzyme in the soleus,
      increased glycogen branching enzyme in the gastrocnemius and EDL, as well as
      reduced levels of mucle glycogen synthase protein in the three muscles (mean
      ~70%), reflecting a protective mechanism for preventing deleterious glycogen
      accumulation. Additionally, glycogen content was highest in the EDL of
      p.R50X/p.R50X mice. Amongst other findings, the present study shows that the
      expression of the main muscle glycogen regulatory enzymes differs depending on
      the muscle phenotype (slow- vs. fast-twitch) and that even partial GP-MM
      deficiency affects maximal endurance capacity. Our knock-in model might help to
      provide insights into the importance of glycogen on muscle function.

PMID- 25873272
TI  - Uncontrolled Donation After Circulatory Determination of Death Donors (uDCDDs) as
      a Source of Lungs for Transplant.
AB  - In April 2014, the American Journal of Transplantation published a report on the
      first lung transplant in the United States recovered from an uncontrolled
      donation after circulatory determination of death donor (uDCDD), assessed by ex
      vivo lung perfusion (EVLP). The article identified logistical and ethical issues
      related to introduction of lung transplant from uDCDDs. In an open clinical
      trial, we have Food and Drug Administration and Institutional Review Board
      approval to transplant lungs recovered from uDCDDs judged suitable after EVLP.
      Through this project and other experiences with lung recovery from uDCDDs, we
      have identified solutions to many logistical challenges and have addressed
      ethical issues surrounding lung transplant from uDCDDs that were mentioned in
      this case report. Here, we discuss those challenges, including issues related to
      recovery of other solid organs from uDCDDs. Despite logistical challenges, uDCDDs
      could solve the critical shortage of lungs for transplant. Furthermore, by
      avoiding the deleterious impact of brain death and days of positive pressure
      ventilation, and by using opportunities to treat lungs in the decedent or during
      EVLP, lungs recovered from uDCDDs may ultimately prove to be better than lungs
      currently being transplanted from conventional brain-dead organ donors. 

PMID- 25873273
TI  - Effects of ghrelin, leptin and melatonin on the levels of reactive oxygen
      species, antioxidant enzyme activity and viability of the HCT 116 human
      colorectal carcinoma cell line.
AB  - Obesity is associated with an increased risk of certain types of cancer,
      including colon cancer. Adipose tissue is an endocrine organ that produces
      biologically active substances, such as leptin and ghrelin. Recent research has
      suggested that adipose-derived hormones may be associated with mechanisms linked
      to tumorigenesis and cancer progression. Furthermore, previous studies have
      demonstrated that pineal gland-derived melatonin possesses important oncostatic
      and antioxidant properties. The present study aimed to determine the effects of
      the adipokines ghrelin and leptin, and the melatonin on intracellular levels of
      reactive oxygen species (ROS) and the activity of selected antioxidant enzymes,
      such as superoxide dismutase, catalase (CAT) and glutathione peroxidase. The
      effects of these compounds were also determined on the viability of HCT 116 human
      colorectal carcinoma cells in vitro. The pro-oxidant and growth inhibitory
      effects of melatonin resulted in an accumulation of ROS and decreased antioxidant
      capacity in melatonin-treated cells. Ghrelin administration alone caused a
      significant decrease in the levels of ROS, due to an increased activity of CAT in
      the HCT 116 cells. In addition, the present study observed increased lipid
      peroxidation following melatonin treatment, and decreased levels of
      malondialdehyde following ghrelin or leptin treatment. In conclusion, ghrelin,
      leptin and melatonin have various influences on the antioxidant capacity of HCT
      116 cells. Compared with the adipokines, treatment with melatonin increased ROS
      levels and decreased cellular viability.

PMID- 25873275
TI  - Sepsis kills, antimicrobial resistance is real.

PMID- 25873274
TI  - Vertebroplasty for acute painful osteoporotic fractures (VAPOUR): study protocol
      for a randomized controlled trial.
AB  - BACKGROUND: With increasing human longevity there is increasing prevalence of
      osteoporosis and of osteoporotic vertebral fractures. Most vertebral fractures do
      not require medical therapy for pain, but a minority are associated with severe
      pain and disability. Vertebroplasty has been used increasingly for painful acute
      osteoporotic fractures. The best available evidence for vertebroplasty is
      provided by two placebo controlled trials which showed no significant clinical
      benefit of vertebroplasty over placebo. These were not acute fracture trials with
      the majority of fractures in both trials being well beyond the acute time frame
      of 6 weeks. There is evidence from an open label randomized controlled trial of
      vertebroplasty versus conservative therapy in acute fractures suggesting clinical
      efficacy in acute vertebral fractures. METHODS: This is a blinded trial of
      Vertebroplasty for Acute Painful Osteoporotic fractURes - the VAPOUR trial.
      Patients greater than 60 years in age with new severe onset of back pain and
      osteoporotic vertebral fractures of less than 6 weeks duration will be enrolled.
      They will be randomized to receive either vertebroplasty or a placebo procedure.
      Data regarding pain, disability, and quality of life will be collected over a 6
      month period. The enrolled patients and the outcome assessors will remain blinded
      for the duration of the trial. DISCUSSION: The VAPOUR trial will apply similar
      methodology to the previous blinded trials but in a patient group with
      exclusively acute fractures and the most severe pain. TRIAL REGISTRATION:
      ClinicalTrials.gov trial identifier: NCT01482793 registered on 28 November 2011.

PMID- 25873278
TI  - Correlation of the KISA% index and Scheimpflug tomography in 'normal',
      'subclinical', 'keratoconus-suspect' and 'clinically manifest' keratoconus eyes.
AB  - PURPOSE: To analyse tomographic changes in eyes classified as 'normal',
      'keratoconus-suspect' and 'clinically manifest keratoconus' based on the
      established KISA% definition of Rabinowitz and Rasheed and to develop the
      category of 'subclinical keratoconus eyes' to expand the classification into a
      'subtopographic' range. METHODS: Tomographic and topographic analyses of 670 eyes
      performed with a rotating Scheimpflug imaging system (Pentacam((r)), Oculus Inc.,
      Wetzlar, Germany) were retrospectively analysed. Based on the KISA% keratoconus
      classification system, eyes were assigned to a 'normal', 'keratoconus-suspect' or
      'manifest keratoconus' group. In addition, a new group of 'subclinical
      keratoconus eyes' was analysed, comprising unsuspicious fellow eyes of patients
      with keratoconus. T-tests, Wilcoxon rank-sum test, receiver operating
      characteristics (ROC) and robust regression analyses were performed to correlate
      tomographic parameters with the increasing KISA% index. RESULTS: KISA%-grouped
      keratoconus eyes showed robust tomographic changes. By adding the subclinical
      group, although the concurrent topography was unchanged, we were able to
      demonstrate statistically significant changes for almost all tomographic
      parameters (parameters with highest sensitivity/specificity: ART_max,
      [0.69/0.69], BAD_D [0.66/0.66]). The highest coefficient of determination (R(2))
      with the KISA% index was demonstrated for Ele_f_max (R(2) = 0.70), Ele_f_TP (R(2)
      = 0.69), Ele_b_TP (R(2) = 0.69) and BAD_D (R(2) = 0.68). CONCLUSION: We recommend
      the use of the expanded KISA% index (eKISA% index) as the basis for the
      definition of keratoconus and normal groups in future keratoconus research
      projects.

PMID- 25873279
TI  - Simpler compression suture for controlling atonic post-partum hemorrhage.

PMID- 25873280
TI  - Abnormal expression of Forkhead Box J2 (FOXJ2) suppresses migration and invasion
      in extrahepatic cholangiocarcinoma and is associated with prognosis.
AB  - Extrahepatic cholangiocarcinoma (CC) is an aggressive malignancy with dismal
      prognosis and characterized by early invasion, metastasis and postoperative
      recurrence. Therefore, understanding the main molecular mechanisms of this
      malignancy is the key for the development of novel and effective therapeutic
      strategies for extrahepatic CC. Foxj2 is a novel forkhead factor. Several FOX
      family members have been reported to play an important role in tumorigenesis and
      the progression of certain cancers. In this study, real-time quantitative RT-PCR
      (qRT-PCR), western blotting, and immunohistochemical staining were used to
      examine FOXJ2 expression in extrahepatic CC tissues and adjacent normal bile duct
      tissues. The molecular mechanisms of FOXJ2 expression and its effects on cell
      proliferation, migration and invasion were also explored by MTT assay, wound
      healing assay and Transwell assay. The relationships between the FOXJ2 expression
      levels, the clinicopathological factors, and patient survival were investigated.
      FOXJ2 mRNA and protein levels were downregulated in extrahepatic CC tissues
      compared to adjacent normal bile duct tissues. In addition, decreased FOXJ2 was
      associated disease progression in extrahepatic CC samples. Overexpression FOXJ2
      expression markedly inhibited cell proliferation, migration and invasion in
      vitro. FOXJ2 is a transcription factor that has been reported to induce
      epithelial-mesenchymal transition (EMT). These findings indicated that FOXJ2 gene
      played a tumor suppressor role in extrahepatic CC, which proposed this gene as a
      new therapeutic target for extrahepatic CC patients.

PMID- 25873281
TI  - High-temperature stable field emission of B-doped SiC nanoneedle arrays.
AB  - Current emission stability is one of the key issues for field emitters for them
      to be practically applied as electron sources. In the present work, large-scale
      and well-aligned B-doped SiC nanoneedle arrays have been grown on 6H-SiC wafer
      substrates via pyrolysis of polymeric precursors. The measured field emission
      (FE) characteristics suggest that the turn-on fields of the as-synthesized SiC
      nanoneedle arrays are reduced from 1.92 to 0.98 V MUm(-1) with temperature
      increasing from room temperature (RT) to 500  degrees C, suggesting their
      excellent FE performances. The slightly changed current fluctuations (only ~1.3%)
      between RT and 200  degrees C confirm that the present SiC nanoarrays with B
      dopants could be highly stable field emitters to be used in service under harsh
      conditions of high temperatures. 

PMID- 25873282
TI  - A Useful Anatomical Reference Guide for Stem Anteversion during Total Hip
      Arthroplasty in the Dysplastic Hip.
AB  - Computed tomography scans of 50 dysplastic hips were obtained and reconstructed
      using preoperative planning software for total hip arthroplasty. The anteversion
      of the stem implanted parallel to the line connecting the trochanteric fossa and
      the middle of the medial cortex of the femoral neck (T line) was measured. The
      cutting heights of 5mm and 10mm above the lesser trochanter were simulated. The
      mean difference of the anteversion of the stem using the T line and the native
      femoral anteversion was 2.7 degrees  (95% CI: 1.0 degrees -4.5 degrees ) and 3.5
      degrees  (95% CI: 1.5 degrees -5.5 degrees ) at cutting heights of 5mm and 10mm
      respectively. An anteversion using a T line is compatible with native femoral
      anteversion even in developmental dysplasia of the hip. 

PMID- 25873283
TI  - Radiation Exposure during Fluoroscopic Guided Direct Anterior Approach for Total
      Hip Arthroplasty.
AB  - Fluoroscopic guidance is commonly utilized during direct anterior total hip
      arthroplasty (DA THA). The purpose of this study was to measure patient and
      surgeon exposure utilizing this technique. Fifty-one consecutive patients who
      underwent primary DA THA by a single surgeon were prospectively studied.
      Fluoroscopic guidance was utilized according to an established protocol. Dose
      area product (DAP) (Gy-cm(2)) and fluoroscopy time were recorded for each case.
      Surgeon exposure was recorded by a dosimeter. The median DAP was 0.716 Gy-cm(2)
      (range 0.251-1.81). Mean fluoroscopy time was 0.59 minutes. Dosimeter results
      were 10 mrem for all procedures combined. DAP and fluoroscopy times were
      comparable to published values for other fluoroscopically guided hip procedures.
      This information may aid in setting reference dose levels for this procedure.

PMID- 25873284
TI  - The current role of ipratropium bromide in an acute exacerbation of asthma.

PMID- 25873285
TI  - Esophagectomy in elderly patients: which is the best prognostic score?
AB  - Our study aimed to identify the best prognostic score for fitness for surgery and
      postoperative morbidity in elderly patients. A prospectively collected database
      of a consecutive series of patients with esophageal cancer evaluated for possible
      esophagectomy at our unit was analyzed. Fitness for surgery and postoperative
      morbidity were used as measures of outcome. The performances of the Physiological
      and Operative Severity Score for the enUmeration of Mortality and morbidity
      (POSSUM) score, the Charlson Comorbidity Index, the age-related Charlson
      Comorbidity Index (ACCI), the American Society of Anesthesiologists scale and the
      prognostic nutritional index (PNI) were evaluated in elderly patients.
      Discrimination was measured with receiver operating characteristics curve
      analysis; calibration was assessed by the Hosmer-Lemeshow goodness-of-fit test.
      Age did not result a significant predictor for postoperative complications. In
      elderly patients, ACCI predicted the judgment of the multidisciplinary team about
      fitness for surgery with the best discrimination (C-index = 0.94). PNI had the
      best discrimination for postoperative complications (C-index = 0.71) in the
      elderly group. ACCI best predicted the fitness for surgery in elderly patients.
      In elderly patients, the most discriminative prognostic score for postoperative
      complication was PNI, which could be used at admission for surgery to correctly
      inform patients about their risk and, possibly, to take extra precaution in case
      of high risk. 

PMID- 25873286
TI  - Noninvasive fetal genotyping of human platelet antigen-1a using targeted
      massively parallel sequencing.
AB  - BACKGROUND: Fetal human platelet antigen (HPA) genotyping is required to
      determine whether the fetus is at risk and whether prenatal interventions to
      prevent fetal bleeding are required in pregnant women with a history of fetal and
      neonatal alloimmune thrombocytopenia (FNAIT). Methods for noninvasive genotyping
      of HPA alleles with the use of maternal plasma cell-free DNA were published
      recently but do lack internal controls to exclude false-negative results. STUDY
      DESIGN AND METHODS: Cell-free DNA was isolated from plasma of four pregnant women
      with a history of FNAIT caused by anti-HPA-1a and controls. A primer panel was
      designed to target sequences flanking single-nucleotide polymorphisms
      (SNPs)/exonic regions of ITGB3 (HPA-1), ITGA2B (HPA-3), ITGA2 (HPA-5), CD109 (HPA
      15), RHD, RHCE, KEL, DARC, SLC14A1, GYPA, GYPB, and SRY. These regions and eight
      anonymous SNPs were massively parallel sequenced by semiconductor technology.
      RESULTS: The mean (+/-SD) number of reads for targeted SNPs was 5255 (+/-2838).
      Fetal DNA was detected at a median of 4.5 (range, 2-8) polymorphic loci. The mean
      fractional fetal DNA concentration in cell-free maternal plasma was 8.36% (range,
      4.79%-15.9%). For HPA-1, nonmaternal ITGB3 sequences (c.176T, HPA-1a) were
      detected in all HPA-1ab fetuses. One HPA-1bb fetus was unequivocally identified,
      showing the pregnancy was not at risk of FNAIT. CONCLUSION: We have successfully
      established massively parallel sequencing as a novel reliable method for
      noninvasive genotyping of fetal HPA-1a alleles. This technique may also allow the
      safe detection of other fetal blood group polymorphisms frequently involved in
      FNAIT and hemolytic disease of the newborn.

PMID- 25873287
TI  - Automated removal of spurious intermediate cerebral blood flow volumes improves
      image quality among older patients: A clinical arterial spin labeling
      investigation.
AB  - PURPOSE: To evaluate the impact of rejecting intermediate cerebral blood flow
      (CBF) images that are adversely affected by head motion during an arterial spin
      labeling (ASL) acquisition. MATERIALS AND METHODS: Eighty participants were
      recruited, representing a wide age range (14-90 years) and heterogeneous
      cerebrovascular health conditions including bipolar disorder, chronic stroke, and
      moderate to severe white matter hyperintensities of presumed vascular origin.
      Pseudocontinuous ASL and T1 -weigthed anatomical images were acquired on a 3T
      scanner. ASL intermediate CBF images were included based on their contribution to
      the mean estimate, with the goal to maximize CBF detectability in gray matter
      (GM). Simulations were conducted to evaluate the performance of the proposed
      optimization procedure relative to other ASL postprocessing approaches. Clinical
      CBF images were also assessed visually by two experienced neuroradiologists.
      RESULTS: Optimized CBF images (CBFopt ) had significantly greater agreement with
      a synthetic ground truth CBF image and greater CBF detectability relative to the
      other ASL analysis methods (P < 0.05). Moreover, empirical CBFopt images showed a
      significantly improved signal-to-noise ratio relative to CBF images obtained from
      other postprocessing approaches (mean: 12.6%; range 1% to 56%; P < 0.001), and
      this improvement was age-dependent (P = 0.03). Differences between CBF images
      from different analysis procedures were not perceptible by visual inspection,
      while there was a moderate agreement between the ratings (kappa = 0.44, P <
      0.001). CONCLUSION: This study developed an automated head motion threshold-free
      procedure to improve the detection of CBF in GM. The improvement in CBF image
      quality was larger when considering older participants.

PMID- 25873288
TI  - Socioeconomic disparities in preterm birth.

PMID- 25873289
TI  - Early pregnancy maternal vitamin D concentrations and risk of gestational
      diabetes mellitus.

PMID- 25873290
TI  - Visible-light-mediated chan-lam coupling reactions of aryl boronic acids and
      aniline derivatives.
AB  - The copper(II)-catalyzed aerobic oxidative coupling reaction between aryl boronic
      acids and aniline derivatives was found to be improved significantly under
      visible-light-mediated photoredox catalysis. The substrate scope of this
      oxidative Chan-Lam reaction was thus expanded to include electron-deficient aryl
      boronic acids as viable starting materials. 

PMID- 25873291
TI  - Stentless aortic reoperation: New surgical strategy with rapid deployment valves.

PMID- 25873292
TI  - Impact of Acute Intermittent Exercise on Natural Killer Cells in Breast Cancer
      Survivors.
AB  - BACKGROUND: Current research examining the effect of exercise on immune responses
      in cancer survivors is limited. OBJECTIVE: The aim of this pilot study was to
      examine the effect of 1 bout of intermittent exercise on natural killer (NK) cell
      numbers in breast cancer survivors. METHODS: A total of 9 women with stage I to
      III invasive breast cancer who were 3 to 6 months posttreatment and 9 sedentary
      women without a history of cancer completed 10 three-minute intervals of aerobic
      exercise on the cycle ergometer at 60% of VO2peak (peak oxygen uptake). Whole
      blood samples were taken pre-exercise, immediately postexercise, and at 2 hours
      and 24 hours postexercise. NK cell counts were assessed using flow cytometry.
      RESULTS: In both groups, NK cell counts significantly increased immediately
      postexercise compared with pre-exercise (P = .004-.008) and returned to near pre
      exercise levels during recovery (P = .129-.547). Absolute NK cell counts were
      significantly lower in breast cancer survivors immediately postexercise when
      compared with controls (P = .046). CONCLUSIONS: The breast cancer survivor group
      exhibited NK cell responses to 30 minutes of moderate-intensity intermittent
      aerobic exercise that were comparable with that in the group of physically
      similar women without a history of cancer. Immune changes related to cancer
      treatments may be related to the lower absolute NK cell counts observed in the
      breast cancer survivor group. Although the results of this study are preliminary
      in nature, they suggest that this type of exercise does not disrupt this aspect
      of innate immunity in recent breast cancer survivors, thereby supporting current
      exercise recommendations for this population.

PMID- 25873293
TI  - Complementary and Alternative Medicine Use in Cancer Patients in Rural Australia.
AB  - AIM: Numerous studies have demonstrated the high prevalence of complementary and
      alternative medicine (CAM) use in metropolitan cancer cohorts but few have been
      conducted in regional and remote populations. This study aimed to investigate the
      trends and regional variations in CAM use by cancer patients at a regional cancer
      care center in Toowoomba, South East Queensland, Australia. METHODS: All English
      speaking adult cancer patients attending the regional cancer care center were
      invited to participate. Eligible patients were provided a self-administered
      questionnaire that was developed based on published surveys. Ethics approval was
      obtained. RESULTS: Overall 142 patients completed the questionnaire and 68% were
      currently or had previously used at least one form of CAM. CAM users and nonusers
      did not differ significantly by region, age, gender, time since diagnosis,
      income, town size, treatment intent, or metastases. CAM users were more likely to
      have a higher level of education. Concurrent CAM use with conventional treatment
      was reported by approximately half of respondents. The most common reason for CAM
      use was "to improve general physical well-being." The most common sources of CAM
      information were family (31%) and friends (29%). Disclosure of CAM use to either
      the general practitioner or specialist was reported by 46% and 33% of patients,
      respectively. The most common reason for nondisclosure was "doctor never asked."
      CONCLUSION: This study supports previous research that CAM use is as common in
      regional and remote areas as metropolitan areas. Nondisclosure of CAM use to
      health professionals was common. Future research needs to focus on strategies to
      improve communication between patients and health professionals about the use of
      CAM.

PMID- 25873294
TI  - Sleep Quality Improves During Treatment With Bryophyllum pinnatum: An
      Observational Study on Cancer Patients.
AB  - HYPOTHESIS: Cancer patients frequently suffer from poor sleep quality.
      Bryophyllum pinnatum is a herbal medication used in anthroposophic medicine,
      which has been shown to be associated with improvements in sleep quality during
      pregnancy with only few and minor or moderate side-effects reported. In this
      study, the sleep quality of cancer patients during treatment with B pinnatum was
      investigated. STUDY DESIGN: In this prospective, observational study, cancer
      patients suffering from sleep problems were treated with B pinnatum (350 mg
      tablets, corresponding to 50% of leaf pressed juice [Weleda AG, Arlesheim,
      Switzerland], dosage at physician's consideration, but most frequently 2 tablets
      with evening meal and 2 before going to bed). METHODS: Sleep quality (Pittsburgh
      Sleep Quality Index [PSQI]), daily sleepiness (Epworth Sleeping Scale [ESS]), and
      fatigue (Fatigue Severity Scale [FSS]) were assessed at the beginning of the
      treatment and after 3 weeks. Possible adverse drug reactions perceived by the
      patients during the treatment were recorded. From the 28 recruited patients, 20
      completed both questionnaires and were considered in the present analysis. Data
      are expressed as mean +/- standard deviation. RESULTS: Patients were 61 +/- 10.4
      years old and the majority were female (17 out of 20). During treatment with B
      pinnatum, the PSQI decreased from 12.2 +/- 3.62 to 9.1 +/- 3.61 (P < .01), and
      ESS changed from 8.4 +/- 3.18 to 7.1 +/- 3.98 (P < .05). There was no change in
      FSS. The treatment was well tolerated by the majority of patients, with only 6
      patients reporting discomfort that might have been caused by B pinnatum (fatigue
      n = 3, dry throat n = 1, agitation n = 1, difficult digestion n = 1). No serious
      adverse drug reactions were detected. CONCLUSION: B pinnatum may be a suitable
      treatment for sleep problems of cancer patients. Controlled, randomized clinical
      trials of the use of B pinnatum in sleep disorders are urgently needed.

PMID- 25873295
TI  - An Exploratory Study of the Effects of Mind-Body Interventions Targeting Sleep on
      Salivary Oxytocin Levels in Cancer Survivors.
AB  - Cancer survivors experience high levels of distress, associated with a host of
      negative psychological states, including anxiety, depression, and fear of
      recurrence, which often lead to sleep problems and reduction in quality of life
      (QOL) and well-being. As a neuropeptide hormone associated with affiliation,
      calmness, and well-being, oxytocin may be a useful biological measure of changes
      in health outcomes in cancer survivors. In this exploratory study, which
      comprised a subset of participants from a larger study, we evaluated (a) the
      feasibility and reliability of salivary oxytocin (sOT) levels in cancer survivors
      and (b) the effects of 2 sleep-focused mind-body interventions, mind-body
      bridging (MBB) and mindfulness meditation (MM), compared with a sleep hygiene
      education (SHE) control, on changes in sOT levels in 30 cancer survivors with
      self-reported sleep disturbance. Interventions were conducted in 3 sessions, once
      per week for 3 weeks. Saliva samples were collected at baseline, postintervention
      (~1 week after the last session), and at the 2-month follow-up. In this cancer
      survivor group, we found that intra-individual sOT levels were fairly stable
      across the 3 time points, of about 3 months' duration, and mean baseline sOT
      levels did not differ between females and males and were not correlated with age.
      Correlations between baseline sOT and self-report measures were weak; however,
      several of these relationships were in the predicted direction, in which sOT
      levels were negatively associated with sleep problems and depression and
      positively associated with cancer-related QOL and well-being. Regarding
      intervention effects on sOT, baseline-subtracted sOT levels were significantly
      larger at postintervention in the MBB group as compared with those in SHE. In
      this sample of cancer survivors assessed for sOT, at postintervention, greater
      reductions in sleep problems were noted for MBB and MM compared with that of SHE,
      and increases in mindfulness and self-compassion were observed in the MBB group
      compared with those in SHE. The findings in this exploratory study suggest that
      sOT may be a reliable biological measure over time that may provide insight into
      the effects of mind-body interventions on health outcomes in cancer survivors. 

PMID- 25873296
TI  - High-Dose Asian Ginseng (Panax Ginseng) for Cancer-Related Fatigue: A Preliminary
      Report.
AB  - INTRODUCTION AND OBJECTIVE: Cancer-related fatigue (CRF) is the most common and
      severe symptom in patients with cancer. The number and efficacy of available
      treatments for CRF are limited. The objective of this preliminary study was to
      assess the safety of high-dose Panax ginseng (PG) for CRF. METHODS: In this
      prospective, open-label study, 30 patients with CRF (>=4/10) received high-dose
      PG at 800 mg orally daily for 29 days. Frequency and type of side effects were
      determined by the National Cancer Institute's Common Terminology Criteria for
      Adverse Events, version 4.0. Scores on the Functional Assessment of Chronic
      Illness Therapy-Fatigue (FACIT-F) scale, Edmonton Symptom Assessment System
      (ESAS), and Hospital Anxiety and Depression Scale (HADS) were assessed at
      baseline, day 15, and day 29. Global Symptom Evaluation (GSE) was assessed at day
      29. RESULTS: Of the 30 patients enrolled, 24 (80%) were evaluable. The median age
      was 58 years; 50% were females, and 84% were white. No severe (>=grade 3) adverse
      events related to the study drug were reported. Of the 24 evaluable patients, 21
      (87%) had an improved (by >=3 points) FACIT-F score by day 15. The mean ESAS
      score (standard deviation) for well-being improved from 4.67 (2.04) to 3.50
      (2.34) (P = .01374), and mean score for appetite improved from 4.29 (2.79) to
      2.96 (2.46) (P = .0097). GSE score of PG for fatigue was >=3 in 15/24 patients
      (63%) with median improvement of 5. CONCLUSION: PG is safe and improves CRF
      fatigue as well as overall quality of life, appetite, and sleep at night.
      Randomized controlled trials of PG for CRF are justified.

PMID- 25873298
TI  - Contributing factors to the development of childhood asthma: working toward risk
      minimization.
AB  - Asthma is the most common chronic disease in childhood, and considerable research
      has been undertaken to find ways to prevent its development and reduce its
      prevalence. For such interventions to be successful, risk factors for asthma
      emergence should be identified and clearly defined. Data are robust for some of
      them, including atopy, viral infections and exposure to airborne irritants,
      whereas it is less conclusive for others, such as aeroallergen exposure and
      bacterial infections. Several interventions for asthma prevention, including
      avoidance and pharmacotherapy, have been attempted. However, most of them have
      furnished equivocal results. Various issues hinder the establishment of risk
      factors for asthma development and reduce the effectiveness of interventions,
      including the complexity of the disease and the fluidity of the developing
      systems in childhood. In this review, we revisit the evidence on pediatric asthma
      risk factors and prevention and discuss issues that perplex this field. 

PMID- 25873297
TI  - Empathy, culture and self-humanising: Empathising reduces the attribution of
      greater humanness to the self more in Japan than Australia.
AB  - People tend to ascribe greater humanness to themselves than to others. Previous
      research has indicated that this "self-humanising" bias is independent of self
      enhancement and robust across cultures. The present study examined the possible
      role of empathy in reducing this bias in Japan (N = 80) and Australia (N = 80).
      Results showed that unlike Australians, Japanese participants who recalled
      personal experiences of empathising with others were less likely to self-humanise
      than those in a neutral condition. The effect of the empathy manipulation was not
      observed in Australia. The findings suggest that empathy may reduce self-focus
      and enable perceivers to appreciate the full humanness of others, but this effect
      may be culturally contingent. 

PMID- 25873299
TI  - Health, Maintenance, and Recovery of Soft Tissues around Implants.
AB  - BACKGROUND: The health of peri-implant soft tissues is one of the most important
      aspects of osseointegration necessary for the long-term survival of dental
      implants. PURPOSE: To review the process of soft tissue healing around
      osseointegrated implants and discuss the maintenance requirements as well as the
      possible short-comings of peri-implant soft tissue integration. MATERIALS AND
      METHODS: Literature search on the process involved in osseointegration, soft
      tissue healing and currently available treatment modalities was performed and a
      brief description of each process was provided. RESULTS: The peri-implant
      interface has been shown to be less effective than natural teeth in resisting
      bacterial invasion because gingival fiber alignment and reduced vascular supply
      make it more vulnerable to subsequent peri-implant disease and future bone loss
      around implants. And we summarized common procedures which have been shown to be
      effective in preventing peri-implantitis disease progression as well as clinical
      techniques utilized to regenerate soft tissues with bone loss in advanced cases
      of peri-implantitis. CONCLUSION: Due to the difference between peri-implant
      interface and natural teeth, clinicians and patients should pay more attention in
      the maintenance and recovery of soft tissues around implants.

PMID- 25873300
TI  - Regulation of connexin 43 and microRNA expression via beta2-adrenoceptor
      signaling in 1321N1 astrocytoma cells.
AB  - Connexin 43 (Cx43) is the main gap junction protein in astrocytes and exerts the
      same effects on growth inhibition in astrocytoma and glioma as microRNA-146a (miR
      146a) in glioma. beta2-adrenergic receptor (AR) signaling modulates Cx43
      expression in myocytes via components downstream of protein kinase A (PKA) and
      exchange protein directly activated by cAMP (Epac). However, it remains to be
      elucidated how expression of Cx43 is modulated in astrocytes. In the present
      study, 1321N1 astrocytoma cells were treated with beta2-AR signaling agents in
      order to evaluate the expression of Cx43 and miRNAs. RNA and protein were
      extracted from the cells for use in reverse transcription-quantitative polymerase
      chain reaction and western blot analysis, respectively. The results revealed that
      clenbuterol increased miR-146a level and upregulated Cx43 expression via cAMP/PKA
      at the mRNA and protein level. Pre-inhibition of adenyl cyclase decreased
      expression of Cx43 and miR-146a. PKA activation and overexpression of miR-146a in
      A-1321N1 cells increased the expression of Cx43. beta2-AR stimulation and 6Bnz, a
      PKA activator, suppressed oncomiRs miR-155 and miR-27a, while 8-(4
      chlorophenylthio)-2'-O-methyladenosine-3',5'-cyclic monophosphate, an Epac
      activator, increased their levels. The current findings demonstrated that beta2
      AR signaling has growth inhibitory effects via modulation of the cAMP/PKA pathway
      in A-1321N1 cells through increasing the expression level of Cx43 and miR-146a as
      well as decreasing miR-155 and miR-27a levels. Thus, stimulation of the beta2-AR
      and PKA signaling pathway may be a useful approach for astrocytoma therapy.

PMID- 25873301
TI  - Use of the Dietary Guideline Index to assess cardiometabolic risk in adolescents.
AB  - The long-term adherence to the dietary guidelines has not been evaluated against
      emergence of cardiometabolic risks in adolescents with increasing rates of
      obesity. The present study aimed to (1) determine the level of adherence to the
      guidelines using the Australian Dietary Guideline Index for Children and
      Adolescents (DGI-CA) in adolescents of age 14 and 17 years and to (2) examine the
      relationship between their assessed diet quality and concurrently measured
      cardiometabolic risk factors over time. Data were analysed from the Western
      Australian Pregnancy Cohort (Raine) Study. The DGI-CA was determined from a FFQ.
      Anthropometry and fasting biochemical measures were taken using standard
      procedures. Hierarchical linear mixed models examined associations between
      cardiometabolic risk factors and DGI-CA, adjusting for socio-economic status,
      physical activity, BMI, and sex, and examining for interactions. The mean DGI-CA
      scores were 47.1 (SD 10.2) at 14 years (n 1419) and 47.7 (SD 11.0) at 17 years (n
      843), and were not different between sex. There was a significant inverse
      association between DGI-CA and insulin, homeostasis model assessment score and
      heart rate. The DGI-CA was positively associated with BMI (P= 0.029) but
      negatively with waist:hip ratio (P= 0.026). It was not associated with lipids or
      blood pressure, with the exception of a negative association with TAG (P= 0.011).
      The degree of adherence in the Raine Study adolescents was suboptimal but similar
      to the Australian Children's Nutrition and Physical Activity Survey. The present
      study shows that, at any particular time, better diet quality was associated with
      better insulin sensitivity and TAG levels and decreased abdominal fatness.

PMID- 25873302
TI  - MAPK pathway mediates epithelial-mesenchymal transition induced by paraquat in
      alveolar epithelial cells.
AB  - Epithelial-mesenchymal transition (EMT) is believed to be involved in lung
      fibrosis process induced by paraquat (PQ); however, the molecular mechanism of
      this process has not been clearly established. The present study investigated the
      potential involvement of EMT after PQ poisoning. The expressions of EMT markers,
      such as E-cadherin and alpha-smooth muscle actin (alpha-SMA), at multiple time
      points after exposure to different concentrations of PQ were evaluated by western
      blot analysis. Following PQ treatment, EMT induction was observed under
      microscopy. Related fibrosis genes, including Matrix metalloproteinase 2 (MMP-2),
      Matrix metalloproteinase 9 (MMP-9), collagens type I (COL I), and type III (COL
      III), were also evaluated by measuring their mRNA levels using RT-PCR analysis.
      Signaling pathways were analyzed using selective pharmacological inhibitors for
      MAPK. Cell migration ability was evaluated by scratch wound and Transwell assays.
      The data showed that PQ-induced epithelial RLE-6NT cells to develop mesenchymal
      cell characteristics, as indicated by a significant decrease in the epithelial
      marker E-cadherin and a significant increase in the extracellular matrix (ECM)
      marker alpha-smooth muscle actin in a dose and time-dependent manner. Moreover,
      PQ-treated RLE-6NT cells had an EMT-like phenotype with elevated expression of
      MMP-2, MMP-9, and COL I and COL III and enhanced migration ability. Signal
      pathway analysis revealed that PQ-induced EMT led to ERK-1 and Smad2
      phosphorylation through activation of the MAPK pathway. The results of the
      current study indicate that PQ-induced pulmonary fibrosis occurs via EMT, which
      is mediated by the MAPK pathway. This implies that the MAPK pathway is a
      promising therapeutic target in alveolar epithelial cells. (c) 2015 Wiley
      Periodicals, Inc. Environ Toxicol 31: 1407-1414, 2016.

PMID- 25873303
TI  - Vitamin C as an adjuvant for treating major depressive disorder and suicidal
      behavior, a randomized placebo-controlled clinical trial.
AB  - BACKGROUND: There are some animal studies suggesting the possible role of vitamin
      C for treating depression. However, the efficacy of vitamin C for treating adult
      patients with major depressive disorder (MDD) has never been examined. METHODS:
      This 8-week randomized double-blind placebo-controlled clinical trial included
      adult patients with major depressive disorder according to DSM-IV diagnostic
      criteria. Twenty-one patients in the treatment group received citalopram plus
      vitamin C and the 22 patients in the control group received citalopram plus
      placebo. The Hamilton Depression Rating Scale was used to measure depressive
      symptoms at baseline, week 2, week 4, and week 8. We also checked for the
      presence of adverse effects. RESULTS: While depression symptoms decreased in both
      groups during this trial, there was no statistically significant difference
      between the 2 groups (P = .5). The rate of remission, partial response, and
      complete response was not different between the two groups. The rate of adverse
      effects were not different between the two groups. CONCLUSION: Adding vitamin C
      to citalopram did not increase the efficacy of citalopram in MDD patients.
      Vitamin C plus citalopram is as effective as placebo plus citalopram for treating
      adult patients with suicidal behavior. No serious adverse effect for this
      combination was identified during this trial. TRIAL REGISTRATION: This trial was
      registered at http://www.irct.ir . The registration number of this trial was:
      IRCT201312263930N31 . Date registered: 5 July 2014.

PMID- 25873304
TI  - Cystathionine beta-synthase inhibition is a potential therapeutic approach to
      treatment of ischemic injury.
AB  - Hydrogen sulfide (H2S) has been reported to exacerbate stroke outcome in
      experimental models. Cystathionine beta-synthase (CBS) has been implicated as the
      predominant H2S-producing enzyme in central nervous system. When SH-SY5Y cells
      were transfected to overexpress CBS, these cells were able to synthesize H2S when
      exposed to high levels of enzyme substrates but not substrate concentrations that
      may reflect normal physiological conditions. At the same time, these cells
      demonstrated exacerbated cell death when subjected to oxygen and glucose
      deprivation (OGD) together with high substrate concentrations, indicating that
      H2S production has a detrimental effect on cell survival. This effect could be
      abolished by CBS inhibition. The same effect was observed with primary astrocytes
      exposed to OGD and high substrates or sodium hydrosulfide. In addition, CBS was
      upregulated and activated by truncation in primary astrocytes subjected to OGD.
      When rats were subjected to permanent middle cerebral artery occlusion, CBS
      activation was also observed. These results imply that in acute ischemic
      conditions, CBS is upregulated and activated by truncation causing an increased
      production of H2S, which exacerbate the ischemic injuries. Therefore, CBS
      inhibition may be a viable approach to stroke treatment. 

PMID- 25873305
TI  - Divergence in endothelin-1- and bradykinin-activated store-operated calcium entry
      in afferent sensory neurons.
AB  - Endothelin-1 (ET-1) and bradykinin (BK) are endogenous peptides that signal
      through Galphaq/11-protein coupled receptors (GPCRs) to produce nociceptor
      sensitization and pain. Both peptides activate phospholipase C to stimulate
      Ca(2+) accumulation, diacylglycerol production, and protein kinase C activation
      and are rapidly desensitized via a G-protein receptor kinase 2-dependent
      mechanism. However, ET-1 produces a greater response and longer lasting
      nocifensive behavior than BK in multiple models, indicating a potentially
      divergent signaling mechanism in primary afferent sensory neurons. Using cultured
      sensory neurons, we demonstrate significant differences in both Ca(2+) influx and
      Ca(2+) release from intracellular stores following ET-1 and BK treatments. As
      intracellular store depletion may contribute to the regulation of other signaling
      cascades downstream of GPCRs, we concentrated our investigation on store-operated
      Ca(2+) channels. Using pharmacological approaches, we identified transient
      receptor potential canonical channel 3 (TRPC3) as a dominant contributor to
      Ca(2+) influx subsequent to ET-1 treatment. On the other hand, BK treatment
      stimulated Orai1 activation, with only minor input from TRPC3. Taken together,
      data presented here suggest that ET-1 signaling targets TRPC3, generating a
      prolonged Ca(2+) signal that perpetuates nocifensive responses. In contrast,
      Orai1 dominates as the downstream target of BK receptor activation and results in
      transient intracellular Ca(2+) increases and abridged nocifensive responses. 

PMID- 25873306
TI  - AAV-mediated gene delivery in a feline model of Sandhoff disease corrects
      lysosomal storage in the central nervous system.
AB  - Sandhoff disease (SD) is an autosomal recessive neurodegenerative disease caused
      by a mutation in the gene for the beta-subunit of beta-N-acetylhexosaminidase
      (Hex), resulting in the inability to catabolize ganglioside GM2 within the
      lysosomes. SD presents with an accumulation of GM2 and its asialo derivative GA2,
      primarily in the central nervous system. Myelin-enriched glycolipids,
      cerebrosides and sulfatides, are also decreased in SD corresponding with
      dysmyelination. At present, no treatment exists for SD. Previous studies have
      shown the therapeutic benefit of adeno-associated virus (AAV) vector-mediated
      gene therapy in the treatment of SD in murine and feline models. In this study,
      we treated presymptomatic SD cats with AAVrh8 vectors expressing feline Hex in
      the thalamus combined with intracerebroventricular (Thal/ICV) injections. Treated
      animals showed clearly improved neurologic function and quality of life,
      manifested in part by prevention or attenuation of whole-body tremors
      characteristic of untreated animals. Hex activity was significantly elevated,
      whereas storage of GM2 and GA2 was significantly decreased in tissue samples
      taken from the cortex, cerebellum, thalamus, and cervical spinal cord. Treatment
      also increased levels of myelin-enriched cerebrosides and sulfatides in the
      cortex and thalamus. This study demonstrates the therapeutic potential of AAV for
      feline SD and suggests a similar potential for human SD patients. 

PMID- 25873307
TI  - Low-dose sevoflurane promotes hippocampal neurogenesis and facilitates the
      development of dentate gyrus-dependent learning in neonatal rats.
AB  - Huge body of evidences demonstrated that volatile anesthetics affect the
      hippocampal neurogenesis and neurocognitive functions, and most of them showed
      impairment at anesthetic dose. Here, we investigated the effect of low dose
      (1.8%) sevoflurane on hippocampal neurogenesis and dentate gyrus-dependent
      learning. Neonatal rats at postnatal day 4 to 6 (P4-6) were treated with 1.8%
      sevoflurane for 6 hours. Neurogenesis was quantified by bromodeoxyuridine
      labeling and electrophysiology recording. Four and seven weeks after treatment,
      the Morris water maze and contextual-fear discrimination learning tests were
      performed to determine the influence on spatial learning and pattern separation.
      A 6-hour treatment with 1.8% sevoflurane promoted hippocampal neurogenesis and
      increased the survival of newborn cells and the proportion of immature granular
      cells in the dentate gyrus of neonatal rats. Sevoflurane-treated rats performed
      better during the training days of the Morris water maze test and in contextual
      fear discrimination learning test. These results suggest that a subanesthetic
      dose of sevoflurane promotes hippocampal neurogenesis in neonatal rats and
      facilitates their performance in dentate gyrus-dependent learning tasks. 

PMID- 25873308
TI  - Prostaglandin E2 EP2 receptor deletion attenuates intracerebral hemorrhage
      induced brain injury and improves functional recovery.
AB  - Intracerebral hemorrhage (ICH) is a devastating type of stroke characterized by
      bleeding into the brain parenchyma and secondary brain injury resulting from
      strong neuroinflammatory responses to blood components. Production of
      prostaglandin E2 (PGE2) is significantly upregulated following ICH and
      contributes to this inflammatory response in part through its E prostanoid
      receptor subtype 2 (EP2). Signaling through the EP2 receptor has been shown to
      affect outcomes of many acute and chronic neurological disorders; although, not
      yet explored in the context of ICH. Wildtype (WT) and EP2 receptor knockout (EP2(
      /-)) mice were subjected to ICH, and various anatomical and functional outcomes
      were assessed by histology and neurobehavioral testing, respectively. When
      compared with age-matched WT controls, EP2(-/-) mice had 41.9 +/- 4.7% smaller
      ICH-induced brain lesions and displayed significantly less ipsilateral
      hemispheric enlargement and incidence of intraventricular hemorrhage. Anatomical
      outcomes correlated with improved functional recovery as identified by
      neurological deficit scoring. Histological staining was performed to begin
      investigating the mechanisms involved in EP2-mediated neurotoxicity after ICH.
      EP2(-/-) mice exhibited 45.5 +/- 5.8% and 41.4 +/- 8.1% less blood and ferric
      iron accumulation, respectively. Furthermore, significantly less striatal and
      cortical microgliosis, striatal and cortical astrogliosis, blood-brain barrier
      breakdown, and peripheral neutrophil infiltration were seen in EP2(-/-) mice.
      This study is the first to suggest a deleterious role for the PGE2-EP2 signaling
      axis in modulating brain injury, inflammation, and functional recovery following
      ICH. Targeting the EP2 G protein-coupled receptor may represent a new therapeutic
      avenue for the treatment of hemorrhagic stroke.

PMID- 25873310
TI  - Emergence of clusters of CRF02_AG and B human immunodeficiency viral strains
      among men having sex with men exhibiting HIV primary infection in southeastern
      France.
AB  - The number of new HIV diagnoses is increasing in the western world and
      transmission clusters have been recently identified among men having sex with men
      despite Highly Active Antiretroviral Therapy efficacy. The objective of this
      study was to assess temporal trends, epidemiological, clinical and virological
      characteristics of primary HIV infections. A retrospective analysis of 79
      patients presenting primary HIV infections from 2005 to 2012 was performed in
      Marseille University Hospitals, southeastern France. Clinical, epidemiological
      and immunovirological data including phylogeny based on the polymerase gene were
      collected. 65 males and 14 females were enrolled. The main transmission route was
      homosexual contact (60.8%). Patients were mostly infected with subtype B (73.4%)
      and CRF02_AG (21.5%) HIV-1 strains. An increase in the annual number of HIV
      seroconversions among new HIV diagnoses from 5% in 2005 to 11.2% in 2012 (P =
      0.06) and of the proportion of CRF02_AG HIV strains among primary HIV infections
      in 2011-2012 as compared to 2005-2010 (P = 0.055) was observed. Phylogenetic
      analysis revealed four transmission clusters including three transmission
      clusters among men having sex with men: two large clusters of nine CRF02_AG, six
      B HIV strains; and one small cluster of three B HIV strains. Clusters involved
      more frequently men (P = 0.01) belonging to caucasian ethicity (P = 0.05), with a
      higher HIV RNA load at inclusion (P = 0.03). These data highlight the importance
      of improving epidemiological surveillance and of implementing suitable prevention
      strategies to control the spread of HIV transmission among men having sex with
      men.

PMID- 25873312
TI  - Functional membranes via nanoparticle self-assembly.
AB  - This article summarizes a recently developed approach for the preparation of
      membrane materials by the self-assembly of inorganic, polymeric or hybrid
      nanoparticles, with the focus on functional membranes possessing permselectivity.
      Two types of such membranes are discussed, those possessing size and charge
      selectivity suitable for ultra- and nanofiltration and chemoselective separation,
      and those possessing proton or lithium transport properties suitable for fuel
      cell and lithium battery applications, respectively. This article describes the
      preparation methods of nanoparticle membranes, as well as their mechanical,
      molecular, and ionic transport properties. 

PMID- 25873309
TI  - ROS produced by NOX2 control in vitro development of cerebellar granule neurons
      development.
AB  - Reactive oxygen species (ROS) act as signaling molecules that regulate nervous
      system physiology. ROS have been related to neural differentiation,
      neuritogenesis, and programmed cell death. Nevertheless, little is known about
      the mechanisms involved in the regulation of ROS during neuronal development. In
      this study, we evaluated the mechanisms by which ROS are regulated during
      neuronal development and the implications of these molecules in this process.
      Primary cultures of cerebellar granule neurons (CGN) were used to address these
      issues. Our results show that during the first 3 days of CGN development in vitro
      (days in vitro; DIV), the levels of ROS increased, reaching a peak at 2 and 3 DIV
      under depolarizing (25 mM KCl) and nondepolarizing (5 mM KCl) conditions.
      Subsequently, under depolarizing conditions, the ROS levels markedly decreased,
      but in nondepolarizing conditions, the ROS levels increased gradually. This
      correlated with the extent of CGN maturation. Also, antioxidants and NADPH
      oxidases (NOX) inhibitors reduced the expression of Tau and MAP2. On the other
      hand, the levels of glutathione markedly increased at 1 DIV. We inferred that the
      ROS increase at this time is critical for cell survival because glutathione
      depletion leads to axonal degeneration and CGN death only at 2 DIV. During the
      first 3 DIV, NOX2 was upregulated and expressed in filopodia and growth cones,
      which correlated with the hydrogen peroxide (H2O2) distribution in the cell.
      Finally, NOX2 KO CGN showed shorter neurites than wild-type CGN. Taken together,
      these results suggest that the regulation of ROS is critical during the early
      stages of CGN development.

PMID- 25873311
TI  - LRH-1 mediates anti-inflammatory and antifungal phenotype of IL-13-activated
      macrophages through the PPARgamma ligand synthesis.
AB  - Liver receptor homologue-1 (LRH-1) is a nuclear receptor involved in the
      repression of inflammatory processes in the hepatointestinal tract. Here we
      report that LRH-1 is expressed in macrophages and induced by the Th2 cytokine IL
      13 via a mechanism involving STAT6. We show that loss-of-function of LRH-1 in
      macrophages impedes IL-13-induced macrophage polarization due to impaired
      generation of 15-HETE PPARgamma ligands. The incapacity to generate 15-HETE
      metabolites is at least partially caused by the compromised regulation of CYP1A1
      and CYP1B1. Mice with LRH-1-deficient macrophages are, furthermore, highly
      susceptible to gastrointestinal and systemic Candida albicans infection.
      Altogether, these results identify LRH-1 as a critical component of the anti
      inflammatory and fungicidal response of alternatively activated macrophages that
      acts upstream from the IL-13-induced 15-HETE/PPARgamma axis. 

PMID- 25873313
TI  - Electrical Stimulation Modulates the Expression of Multiple Wound Healing Genes
      in Primary Human Dermal Fibroblasts.
AB  - This study profiled multiple human dermal fibroblast wound-healing genes in
      response to electrical stimulation (ES) by using an RT(2) profiler PCR-Array
      system. Primary human skin fibroblasts were seeded on heparin (HE)-bioactivated
      polypyrrole (PPy)/poly(l-lactic acid) (PLLA) conductive membranes, cultured, and
      subsequently exposed to ES of 50 or 200 mV/mm for 6 h. Following ES, the cells
      were used to extract RNA for gene profiling, and culture supernatants were used
      to measure the level of the different wound healing mediators. A total of 57
      genes were affected (activated/repressed) by ES; among these, 49 were upregulated
      and 8 were downregulated. ES intensities at 50 and 200 mV/mm activated/repressed
      different genes. The ES-modulated genes are involved in cell adhesion, remodeling
      and spreading, cytoskeletal activity, extracellular matrix metabolism, production
      of inflammatory cytokines/chemokines and growth factors, as well as signal
      transduction. The expression of several genes was supported by protein
      production. Protein analyses showed that ES increased CCL7, KGF, and TIMP2, but
      reduced MMP2. This study demonstrated that ES modulates the expression of a
      variety of genes involved in the wound healing process, confirming that ES is a
      useful tool in regenerative medicine.

PMID- 25873314
TI  - Potential effects of interferon regulatory factor 4 in a murine model of
      polyinosinic-polycytidylic acid-induced embryo resorption.
AB  - Interferon regulatory factor (IRF) 4 has been reported to modulate Toll-like
      receptor (TLR) signalling. Polyinosinic-polycytidylic acid (poly(I:C)) can be
      specifically recognised by TLR3, triggering the innate immune response and
      subsequently resulting in pregnancy loss. In the present study, poly(I:C) was
      administered to mice with or without TLR3 blockade. Chemokine (C-X-C motif)
      receptor 4 (CXCR4) expression was measured with or without chemokine (C-X-C
      motif) ligand 12 (CXCL12) inhibition. In cultured murine splenic mononuclear
      cells, IRF4 was knocked down by a specific short interference (si) RNA. IRF4 mRNA
      and protein levels and T helper (Th) 17 cell frequencies in the poly(I:C)-treated
      group were significantly higher than in the phosphate-buffered saline (PBS)
      treated control group, and were correlated with a significantly higher embryo
      resorption rate. Interleukin (IL)-17A and IL-21 levels were markedly lower in the
      IRF4 siRNA-treated group than in the non-specific siRNA- or vehicle control
      treated groups. The CXCR4+ cell frequency was significantly higher among IRF4+
      uterine mononuclear and granular cells (UMGCs) compared with IRF4- cells.
      Inhibition of CXCL12 significantly abrogated poly(I:C)-induced increases in the
      frequency of IRF4+CXCR4+ cells in UMGCs. IRF4 might play a critical role in TLR3
      signalling, which mediates Th17 cell activation and upregulates the expression of
      IL-17A and IL-21, which results in pregnancy loss. CXCL12 may modulate
      IRF4+CXCR4+ cell migration at the fetomaternal interface. TLR3 and IRF4 blockade
      could potentially prevent spontaneous abortion under certain conditions.

PMID- 25873315
TI  - Solvent-induced secondary building unit (SBU) variations in a series of Cu(II)
      metal-organic frameworks derived from a bifunctional ligand.
AB  - The role of auxiliary solvents in the formation of metal-organic frameworks
      (MOFs) has been studied for a series of copper-based framework systems. Herein we
      show the formation of three different 3D ordered frameworks with the formulae
      {[Cu4(cpt)4Cl4].2DMF.dioxane.3H2O}n (1), {[Cu8(cpt)4(Hcpt)2Cl7(MU3
      OH)2(H2O)4]Cl3.4CH3CN}n (2), and {[Cu8(cpt)4Cl4(MU3-OH)2(MU4
      O)2]Cl2.4H2O.2CH3CN.3MeOH}n (3) [Hcpt = 4-(4-carboxyphenyl)-1,2,4-triazole],
      respectively, from the same reaction mixture through varying auxiliary solvents
      of the medium. These MOFs were fully characterized by single-crystal X-ray
      diffraction, showing interesting secondary building unit (SBU) variations. The
      varied SBUs not only bring different framework architectures to these MOFs, but
      also affect their framework stability. Gas sorption studies of MOF 3 reveal high
      CO2-N2 selectivity at 298 K and 0.16 bar (a typical partial pressure of CO2 in an
      industrial flue gas). A high isosteric heat of adsorption (Qst) at zero loading
      (53 kJ mol(-1)) was also observed in MOF 3.

PMID- 25873317
TI  - Optical cavity-assisted broadband optical transparency of a plasmonic metal film.
AB  - We theoretically present a powerful method to achieve a continuous metal film
      structure with broadband optical transparency via introducing a dielectric Fabry
      Perot (FP) cavity. An incident optical field could be efficiently coupled and
      confined with the strong localized plasmons by the non-close-packed plasmonic
      crystal at the input part and could then become re-radiated output via the
      transmission channel supported by the dielectric cavity. The formed photonic
      plasmonic system could therefore make the seamless metal film structure have a
      superior near-unity transparency (up to 97%) response and a broadband transparent
      spectrum with bandwidth >245 nm (with transmittance >90%) in the optical regime.
      The observed optical properties of the proposed structure can be highly tuned via
      varying the structural parameters. Based on the colloidal assembly method, the
      proposed plasmonic crystal can be fabricated in a large area. In addition, the
      achieved optical transparency can be retained in the extremely roughed metal film
      structure. Thereby, the findings could offer a feasible way to achieve a
      broadband transparent metal film structure and hold potential applications in
      transparent electrodes, touch screens and interactive electronics. 

PMID- 25873316
TI  - Determination of trimethylamine-N-oxide in combination with L-carnitine and gamma
      butyrobetaine in human plasma by UPLC/MS/MS.
AB  - An ultra-high-performance liquid chromatography-mass spectrometry (UPLC/MS/MS)
      method was developed and validated for the quantification of trimethylamine-N
      oxide (TMAO) simultaneously with TMAO-related molecules L-carnitine and gamma
      butyrobetaine (GBB) in human blood plasma. The separation of analytes was
      achieved using a Hydrophilic interaction liquid chromatography (HILIC)-type
      column with ammonium acetate-acetonitrile as the mobile phase. TMAO determination
      was validated according to valid US Food and Drug Administration guidelines. The
      developed method was successfully applied to plasma samples from healthy
      volunteers.

PMID- 25873318
TI  - Reactivation of antibiosis in the entomogenous fungus Chrysoporthe sp. SNB-CN74.
AB  - Chrysoporthe sp. SNB-CN74 was isolated from a Nasutitermes corniger nest, and its
      ethyl acetate extract was found to exhibit very strong antibacterial activity.
      Two antibacterial metabolites were isolated, (-)-R-skyrin (2) and (+)-rugulosin A
      (3). Eventually, the fungus lost its antibiotic potential when subcultured, and
      the use of yeast extract induced the re-expression of these two antibiotics.
      Yeast extract possibly activated a cryptic pathway by mimicking the presence of
      an ecological competitor. 

PMID- 25873319
TI  - Two new anthraquinones from the soil fungus Penicillium purpurogenum SC0070.

PMID- 25873320
TI  - Liamocin oil from Aureobasidium pullulans has antibacterial activity with
      specificity for species of Streptococcus.

PMID- 25873321
TI  - Structural biological study of self-resistance determinants in antibiotic
      producing actinomycetes.
AB  - As antibiotics act to inhibit the growth of bacteria, the drugs are useful for
      treating bacterial infectious diseases. However, microorganisms that produce
      antibiotics must be protected from the lethal effect of their own antibiotic
      product. In this review, the fruit of our group's current research on self
      protection mechanisms of Streptomyces producing antibiotics that inhibit DNA,
      protein and bacterial cell wall syntheses will be described. 

PMID- 25873322
TI  - Investigation of the molecular epidemiology of Acinetobacter baumannii isolated
      from patients and environmental contamination.
AB  - The objective of this work was to investigate correlations between Acinetobacter
      baumannii isolates from neurosurgical intensive care unit patients and its
      environment. This is a prospective, observational study. The minimal inhibitory
      concentrations of antimicrobial agents against 27 clinical and 28 environmental
      isolates were determined by the agar dilution method. Molecular genotyping was
      performed by enterobacterial repetitive intergenic consensus PCR (ERIC-PCR),
      pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST).
      The presence of carbapenemase and metallo-beta-lactamase genes were analyzed by
      specific PCRs and DNA sequencing. From the clinical A. baumannii isolates, 25.9%
      were found resistant to minocycline, 51.9% to cefoperazone-sulbactam, 59.3% to
      imipenem and 70% resistant to other antimicrobial agents. Environmental isolates
      were more sensitive compared with clinical isolates (P<0.05). Twenty-seven
      clinical isolates comprised three ERIC-PCR genotypes, four major PFGE pulsotypes
      and five distinct MLST sequence types (STs) (ST208, ST368, ST191, ST195, ST540),
      all belonging to CC92 with only one locus (gpi) difference among them. Twenty
      eight environmental isolates showed more diverse genetic types than clinical
      isolates and comprised six ERIC-PCR groups, nine PFGE groups and two main STs
      (ST208, ST229). Four clinical and 15 environmental isolates could not be
      identified by MLST and were assigned to non-clonal STs. We identified the
      presence of the blaOXA-23 carbapenemase encoding gene in most of the clinical
      (21/27) but fewer in the environmental isolates (3/28). The A. baumannii strains
      isolated from patients were genetically similar to the environmental strains,
      with CC92 members as the major fraction but with different antibiotic
      susceptibilities. 

PMID- 25873323
TI  - Independent controls of differently-polarized reflected waves by anisotropic
      metasurfaces.
AB  - We propose a kind of anisotropic planar metasurface, which has capacity to
      manipulate the orthogonally-polarized electromagnetic waves independently in the
      reflection mode. The metasurface is composed of orthogonally I-shaped structures
      and a metal-grounded plane spaced by a dielectric isolator, with the thickness of
      about 1/15 wavelength. The normally incident linear-polarized waves will be
      totally reflected by the metal plane, but the reflected phases of x- and y
      polarized waves can be controlled independently by the orthogonally I-shaped
      structures. Based on this principle, we design four functional devices using the
      anisotropic metasurfaces to realize polarization beam splitting, beam deflection,
      and linear-to-circular polarization conversion with a deflection angle,
      respectively. Good performances have been observed from both simulation and
      measurement results, which show good capacity of the anisotropic metasurfaces to
      manipulate the x- and y-polarized reflected waves independently. 

PMID- 25873324
TI  - False positive cervical smear in a patient with pernicious anaemia.

PMID- 25873325
TI  - When is a nodule more than a nodule?

PMID- 25873326
TI  - Test purchase, synthesis, and characterization of 2-methoxydiphenidine (MXP) and
      differentiation from its meta- and para-substituted isomers.
AB  - The structurally diverse nature of the 1,2-diphenylethylamine template provides
      access to a range of substances for drug discovery work but some have attracted
      attention as 'research chemicals'. The most recent examples include diphenidine,
      i.e. 1-(1,2-diphenylethyl)piperidine and 2-methoxydiphenidine, i.e. 1-[1-(2
      methoxyphenyl)-2-phenylethyl]piperidine (MXP, methoxyphenidine, 2-MXP) that have
      been associated with uncompetitive N-methyl-D-aspartate (NMDA) receptor
      antagonist activity. Analytical challenges encountered during chemical analysis
      include the presence of positional isomers. Three powdered samples suspected to
      contain 2-MXP were obtained from three Internet retailers in the United Kingdom
      and subjected to analytical characterization by gas chromatography (GC) and high
      performance liquid chromatography (HPLC) coupled to various forms of mass
      spectrometry (MS). Nuclear magnetic resonance spectroscopy, infrared spectroscopy
      and thin layer chromatography were also employed. This was supported by the
      synthesis of all three isomers (2-, 3- and 4-MXP) by two different synthetic
      routes. The analytical data obtained for the three purchased samples were
      consistent with the synthesized 2-MXP standard and the differentiation between
      the isomers was possible. Distinct stability differences were observed for all
      three isomers during in-source collision-induced dissociation of the protonated
      molecule when employing detection under HPLC selected-ion monitoring detection,
      which added to the ability to differentiate between them. Furthermore, the
      analysis of a 2-MXP tablet by matrix assisted inlet ionization Orbitrap mass
      spectrometry confirmed that it was possible to detect the protonated molecule of
      2-MXP directly from the tablet surface following addition of 3-nitrobenzonitrile
      as the matrix.

PMID- 25873327
TI  - On the importance of cavity-length and heat dissipation in GaN-based vertical
      cavity surface-emitting lasers.
AB  - Cavity-length dependence of the property of optically pumped GaN-based vertical
      cavity surface-emitting lasers (VCSELs) with two dielectric distributed Bragg
      reflectors was investigated. The cavity lengths were well controlled by employing
      etching with inductively coupled plasma and chemical mechanical polishing. It was
      found that the lasing characteristics including threshold, slope efficiency and
      spontaneous emission coupling factor were substantially improved with reducing
      the cavity length. In comparison with the device pumped by a 400 nm pulsed laser,
      the lasing spectrum was featured by a red shift and simultaneous broadening with
      increasing the pumping energy of a 355 nm pulsed laser. Moreover, the lasing
      threshold was much higher when pumped by a 355 nm pulsed laser. These were
      explained by taking into account of the significant heating effect under 355 nm
      pumping. Our results demonstrate that a short cavity length and good heat
      dissipation are essential to GaN-based VCSELs. 

PMID- 25873328
TI  - GATA4 transgenic mice as an in vivo model of congenital heart disease.
AB  - Our previous study indicated that 8 patients from a family with a history of
      congenital heart disease had simple atrial septal defect (ASD) and carried the
      same mutation at codon 310 in the GATA4 gene. In the present study, to identify
      the functional defects caused by this mutation in an in vivo model, the transgene
      DNA constructs were microinjected into mice to generate a transgenic mouse model.
      The mice were genotyped using PCR and DNA sequencing. Protein expression was
      measured by western blot analysis. qPCR was used to determine the copy number of
      the transgenes. The heart tissue was fixed and sectioned by conventional
      procedures. The Vevo 2000 system was used to perform echocardiography on the
      mice. The expression of GATA4 target genes was measured using the real-time PCR
      system. The incidence of ASD in the heterozygous transgenic mice was found to be
      greater than that in the wild-type control mice (P<0.05). In addition, the
      expression of alpha-myosin heavy chain (alpha-MHC) in the heart tissues from the
      homozygous mice was lower than that in the heart tissues from their wild-type
      littermates (P<0.05). In conclusion, these results suggest that the introduction
      of GATA4 M310V negatively affects the normal expression of alpha-MHC. In
      accordance with previous findings on GATA4 mutation screening and in vitro
      experiments, this study confirms that GATA4 M310V mutation may lead to the
      development of the congenital heart defect, ASD.

PMID- 25873329
TI  - Aberrant alternative splicing pattern of ADAR2 downregulates adenosine-to-inosine
      editing in glioma.
AB  - Adenosine-to-inosine (A-to-I) RNA editing is the most common type of RNA editing
      in mammals, and is catalyzed by adenosine deaminases acting on RNA (ADARs). ADAR2
      is the main enzyme responsible for A-to-I editing in humans, and A-to-I
      underediting at the glutamine (Q)/arginine (R) site of the glutamate receptor
      subunit B (GluR-B) is associated with the pathogenesis and invasiveness of
      glioma. The level of ADAR2 mRNA expression and the alternative splicing of the
      ADAR2 pre-mRNA both affect the catalytic activity of ADAR2. However, reports of
      ADAR2 mRNA expression in glioma are inconsistent. The mechanism regulating ADAR2
      pre-mRNA splicing is also unknown. In this study, we explored the deregulation of
      A-to-I RNA editing in glioma. We confirmed the underediting at the Q/R site of
      GluR-B mRNA in the glioma cell lines U87, U251 and A172 compared with that in
      normal human astrocytes (NHAs) HA1800. However, we demonstrated with reverse
      transcription (RT-PCR) and quantitative PCR (qPCR) that the expression of ADAR2
      mRNA was not significantly altered in the glioma cell lines. Three alternative
      splicing sites are utilized in the glioma cell lines and NHAs: the first, located
      between exons -1 and 1, causes the inclusion of exon 1a; the second causes the
      removal of exon 2, which encodes two double-stranded RNA-binding domains; and the
      third, located between exons 4 and 6, causes the inclusion of alternative exon
      5a, introducing a 120-nucleotide coding Alu-repeat sequence in frame. However,
      the expression ratio of two types of transcripts (with and without exon 5a) was
      altered in the glioma cells. Transcripts with exon 5a, which generate an ADAR2
      isoform with ~50% reduced activity, were predominantly expressed in the glioma
      cell lines, whereas transcripts without exon 5a were predominantly expressed in
      the NHAs. From these results, we conclude that this aberrant alternative splicing
      pattern of ADAR2 downregulates A-to-I editing in glioma.

PMID- 25873330
TI  - Effect of age on the efficacy of adjuvant chemotherapy for resected non-small
      cell lung cancer.
AB  - BACKGROUND: Adjuvant chemotherapy after surgical resection improves outcomes for
      patients with early-stage non-small cell lung cancer (NSCLC). To the authors'
      knowledge, there are no published prospective trials to date of adjuvant
      chemotherapy after surgical resection administered exclusively in older patients.
      In the current study, the authors sought to evaluate the efficacy of adjuvant
      chemotherapy in older patients in a Veterans Health Administration cohort.
      METHODS: Patients who underwent surgical resection for American Joint Committee
      on Cancer stages IB to III NSCLC between 2001 and 2011 were analyzed. Data
      regarding patient demographics and comorbidities, tumor characteristics, and
      primary treatment were collected. Patients were divided into 2 groups based on
      age at diagnosis: those aged <70 years and those aged >=70 years. The primary
      exposure was use of adjuvant chemotherapy. A Cox proportional hazards model was
      used to estimate the significance of patient characteristics. Survival curves
      were estimated using the Kaplan-Meier method and group comparisons were performed
      using the log-rank test. RESULTS: The analysis included 7593 patients who
      underwent surgical resection for stage IB to stage III NSCLC. Among these, 2897
      patients (38%) were aged >=70 years. The percentage of older patients who
      received adjuvant chemotherapy was approximately one-half that of younger
      patients who did so (15.3% vs 31.6%; P<.0001). Carboplatin-based doublets were
      used most often in all patients (64.6%). Both younger patients (hazard ratio,
      0.79; 95% confidence interval, 0.72-0.86) and older patients (hazard ratio, 0.81;
      95% confidence interval, 0.71-0.92) were found to have a lower risk of death with
      receipt of adjuvant chemotherapy. CONCLUSIONS: Older patients derive a similar
      magnitude of benefit from adjuvant chemotherapy as younger patients and therefore
      adjuvant chemotherapy should not be withheld based on age alone.

PMID- 25873331
TI  - Evaluation of gene expression changes in human primary lung epithelial cells
      following 24-hr exposures to inorganic arsenic and its methylated metabolites and
      to arsenic trioxide.
AB  - The concentration response for altered gene expression in primary lung epithelial
      cells was determined following two treatments with arsenicals: (1) a mixture of
      trivalent arsenic compounds representative of urinary arsenic concentrations in
      exposed human populations, and (2) arsenite (As2 O3 ) a common form of inhaled
      arsenic dust that is frequently used in both in vivo and in vitro experimental
      exposures. Biochemical assays did not detect any evidence of cytotoxicity at the
      concentrations used, apart from a concentration-related increase in cellular heme
      oxygenase that was also indicated by the genomic analysis. Cell signal pathway
      enrichment analysis indicated similar responses to both treatments, with
      concentration-related responses in pathways related to cell adhesion,
      cytoskeleton remodeling, development (morphogenesis), cell cycle control, and to
      a lesser extent inflammatory responses. These cellular responses to arsenic were
      consistent with those observed in a previous study with primary uroepithelial
      cells. Benchmark dose analysis also demonstrated similar potency of the two
      treatments as well as comparable sensitivity of the two cell types. A number of
      genes showing similar concentration-dependent expression across individuals in
      both bladder and lung cells were identified, including heme oxygenase 1,
      thioredoxin reductase, DNA damage binding protein 2, and thrombomodulin. The data
      on human primary lung cells from this study, together with the data from human
      primary uroepithelial cells, support a conclusion that biological responses to
      arsenic by human cells under study conditions are unlikely to occur at
      concentrations below 0.1 uM. Environ. Mol. Mutagen. 56:477-490, 2015. (c) 2015
      Wiley Periodicals, Inc.

PMID- 25873332
TI  - Colloidal synthesis and optical properties of type-II CdSe-CdTe and inverted CdTe
      CdSe core-wing heteronanoplatelets.
AB  - We developed colloidal synthesis to investigate the structural and electronic
      properties of CdSe-CdTe and inverted CdTe-CdSe heteronanoplatelets and
      experimentally demonstrate that the overgrowth of cadmium selenide or cadmium
      telluride core nanoplatelets with counterpartner chalcogenide wings leads to type
      II heteronanoplatelets with emission energies defined by the bandgaps of the CdSe
      and CdTe platelets and the characteristic band offsets. The observed conduction
      and valence band offsets of 0.36 eV and 0.56 eV are in line with theoretical
      predictions. The presented type-II heteronanoplatelets exhibit efficient
      spatially indirect radiative exciton recombination with a quantum yield as high
      as 23%. While the exciton lifetime is strongly prolonged in the investigated type
      II 2D systems with respect to 2D type-I systems, the occurring 2D giant
      oscillator strength (GOST) effect still leads to a fast and efficient exciton
      recombination. This makes type-II heteronanoplatelets interesting candidates for
      low threshold lasing applications and photovoltaics. 

PMID- 25873333
TI  - Mating system as a barrier to gene flow.
AB  - Understanding mating system as one of reproductive isolating barriers remains
      important although this barrier is classified in a different sense from
      behavioral, ecological, and mechanical isolating barriers. Selfing enhances
      incipient speciation while outcrossing facilitates species integrity. Here, I
      study how mating system affects gene exchanges between genetically diverging
      species in a hybrid zone. Results show that a predominant selfing species has a
      greater barrier to selective gene flow than does a predominant outcrossing
      species. Barrier to neutral gene flow convexly changes with the selfing rate due
      to linkage disequilibrium, with a maximum at around intermediate selfing rate.
      Asymmetric transient or steady-state barriers to neutral gene flow occur between
      two sides of a hybrid zone when the neutral gene is affected by its linked
      selective gene whose alternative alleles are adaptive to heterogeneous habitats.
      Selfing interacts with both a physical barrier and a density-dependent ecological
      regulation (a logarithmic model) to strengthen the barriers to neutral and
      selective gene flow. This theory helps to interpret incipient speciation driven
      by selfing or to explain the asymmetric gene flow or unequal genomic mixtures
      between closely related species caused by their asymmetric mating systems in
      natural hybrid zones. 

PMID- 25873335
TI  - Assessment of the vestibuloocular reflex in fighter pilots with the video head
      impulse test.
AB  - CONCLUSION: There were no changes in the function of the six semicircular canals
      in active fighter pilots, through the use of the video head impulse test (vHIT).
      These results suggest that the vestibuloocular reflex (VOR) works well at the
      high frequencies related to the natural head movements in this population.
      OBJECTIVES/HYPOTHESIS: The vestibular function in pilots has been reported as
      being different from that of other normal subjects. These differences are
      attributed to adaptation of the vestibuloocular reflex (VOR) or by habituation.
      These studies were conducted with caloric and/or rotatory tests and were limited
      to the lateral semicircular canals. The aim of the present study was to verify
      the occurrence of high frequency changes in the function of the six semicircular
      canals in active fighter pilots, through the use of the video head impulse test
      (vHIT). STUDY DESIGN: Cross-sectional design. METHODS: The subjects participating
      in this study were divided in three groups, according to their flight experience.
      The control group (Group 1) consisted of 20 soldiers with no experience of in
      flight training. For the test subjects 14 fighter pilots were selected and
      divided into two groups. Group 2 included the pilots with 1000-2000 hours of
      flight experience and Group 3 included pilots with 2001-3000 hours of flight
      experience. They were all submitted to a video head impulse test and the gains of
      the six semicircular canals were analysed. RESULTS: There were significantly low
      gain values (p < 0,013) only in the left posterior semicircular canal in the
      control group as compared with the subject groups. However, there were no
      significant differences in gain values between the two groups of the active
      pilots.

PMID- 25873334
TI  - The effectiveness of Tai Chi for patients with Parkinson's disease: study
      protocol for a randomized controlled trial.
AB  - BACKGROUND: Parkinson's disease (PD) is a common degenerative neurological
      disorder that causes loss of independence and decreased quality of life. The
      prevalence of PD tends to increase with age. In China, the morbidity rate of PD
      among people aged more than 65 years old is 1.70%. As an important component of
      traditional Chinese Qigong exercises, Tai Chi is a popular and safe exercise,
      especially for older adults in China. And it may result in promising gains for PD
      patients. However, current evidence is insufficient to inform the use of Tai Chi
      in the management of PD. Therefore, the aim of this trial is to systematically
      evaluate the effect of Tai Chi on PD and determine whether Tai Chi is an eligible
      exercise program for Chinese PD patients. METHODS/DESIGN: A single-blind,
      parallel randomized controlled trial will be conducted. One hundred and forty-two
      patients with PD will be randomly assigned to a Tai Chi group (n = 71) or routine
      exercise group (n = 71). Subjects will participate in supervised study programs 3
      times per week for 2 months and will be followed for an additional 6 months after
      formal training stops. The primary outcome measures include Berg Balance Scale,
      Timed Up and Go Test and Six-Minute Walk Test, which are known to be valid and
      reliable clinical instruments. The Unified Parkinson's Disease Rating Scale Motor
      Section and Parkinson's Disease Questionnaire-39 will be used as the secondary
      outcome measure. All outcomes will be measured at baseline, 2 and 8 months. The
      sample for this trial (N = 142) will provide relevant information to detect the
      improvement of balance, gait and quality of life in either of the 2 exercise
      groups. DISCUSSION: Findings from this study will provide insights into the
      effects of Tai Chi in people with PD. The information gained from this project
      has the potential to influence the clinical decisions of Chinese doctors, and
      will provide clear evidence as to whether Tai Chi should be advocated in people
      with PD. TRIAL REGISTRATION: The trial was registered at ( ChiCTR-TRC-14004549 )
      on 22 April 2014.

PMID- 25873336
TI  - The role of solvent swelling in the self-assembly of squalene based
      nanomedicines.
AB  - Squalene based nanoparticles obtained via nanoprecipitation are promising
      candidates as efficient anti-cancer drugs. In order to highlight their
      preparation process and to facilitate further clinical translation, the present
      study enlightens the paramount role of the solvent in the formation of these
      nanomedicines. Three different squalene-based nanoparticles, i.e. squalenic acid,
      deoxycytidine squalene and gemcitabine squalene, have been investigated before
      and after organic solvent evaporation. Size and structural analysis by Small
      Angle Neutron Scattering revealed that droplets' size was uniquely controlled by
      the solvent composition (ethanol-water), which evolved during their gradual
      formation. The particles were preferably swollen by water and the swelling
      increased when less ethanol was present. Either coalescence or fragmentation was
      observed depending on the increase or decrease of the ethanol content, supporting
      an equilibrium control of the size. Moreover, a high water swelling was observed
      for the three local organization of the nanodroplets (hexagonal for gemcitabine
      squalene, cubic for deoxycytidine and not structured for squalenic acid) and
      could be the source of the previously reported efficiency of related anti-cancer
      squalene based nanomedicines. 

PMID- 25873337
TI  - Quantification of nanomaterial bioconjugation based on electrophoretic mobility
      shift.
AB  - Electrophoretic mobility shift assay (EMSA) is a well-established technique to
      monitor interactions between biomolecules particularly DNA and proteins. Even
      though numerous variations of this method have been presented, challenges in the
      form of detection sensitivity and/or variations in the stability of the formed
      complex still remain. With advances in the area of nanomaterials improvements in
      EMSA have been also suggested. Recently, Zhang and Wang (Electrophoresis 2015,
      36, 1011-1015) presented electrophoretic mobility shift method for determination
      of number of DNA molecules conjugated to quantum dots (QDs), which was further
      utilized for calculation of enzymatic activity, sequence specific DNA detection,
      and neutral molecule quantification. 

PMID- 25873339
TI  - A modular approach to the total synthesis of tunicamycins.
AB  - The tunicamycins constitute a delicate mimic of the bisubstrate intermediates of
      N-acetyl-D-hexosamine-1-phosphate translocases and thus inhibit bacterial cell
      wall synthesis and the N glycosylation of eukaryotic proteins. An efficient
      approach to the synthesis of this unique type of nucleoside antibiotics is now
      reported and features the assembly of five modules in a highly stereoselective
      and robust manner. A Mukaiyama aldol reaction, intramolecular acetal formation,
      gold(I)-catalyzed O and N glycosylation, and final N acylation were used as the
      key steps. 

PMID- 25873338
TI  - Comparison between the standard and a new alternative format of the Summary-of
      Findings tables in Cochrane review users: study protocol for a randomized
      controlled trial.
AB  - BACKGROUND: Systematic reviews represent one of the most important tools for
      knowledge translation but users often struggle with understanding and
      interpreting their results. GRADE Summary-of-Findings tables have been developed
      to display results of systematic reviews in a concise and transparent manner. The
      current format of the Summary-of-Findings tables for presenting risks and quality
      of evidence improves understanding and assists users with finding key information
      from the systematic review. However, it has been suggested that additional
      methods to present risks and display results in the Summary-of-Findings tables
      are needed. METHODS/DESIGN: We will conduct a non-inferiority parallel-armed
      randomized controlled trial to determine whether an alternative format to present
      risks and display Summary-of-Findings tables is not inferior compared to the
      current standard format. We will measure participant understanding, accessibility
      of the information, satisfaction, and preference for both formats. We will invite
      systematic review users to participate (that is clinicians, guideline developers,
      and researchers). The data collection process will be undertaken using the online
      'Survey Monkey' system. For the primary outcome understanding, non-inferiority of
      the alternative format (Table A) to the current standard format (Table C) of
      Summary-of-Findings tables will be claimed if the upper limit of a 1-sided 95%
      confidence interval (for the difference of proportion of participants answering
      correctly a given question) excluded a difference in favor of the current format
      of more than 10%. DISCUSSION: This study represents an effort to provide
      systematic reviewers with additional options to display review results using
      Summary-of-Findings tables. In this way, review authors will have a variety of
      methods to present risks and more flexibility to choose the most appropriate
      table features to display (that is optional columns, risks expressions,
      complementary methods to display continuous outcomes, and so on). TRIALS
      REGISTRATION: NCT02022631 (21 December 2013).

PMID- 25873340
TI  - Raman Imaging from Microscopy to Nanoscopy, and to Macroscopy.
AB  - Raman spectroscopy can not only provide intrinsic fingerprint information about a
      sample, but also utilize the merits of the narrow bandwidth and low background of
      Raman spectra, offering itself as a promising multiplex analytical technique.
      Raman microscopy has become particularly attractive recently because it has
      demonstrated itself as an important imaging technique for various samples, from
      biological samples and chemical systems to industrially important silicon-based
      wafers. In this Concept article, some of the most recent advances in Raman
      imaging techniques are critically reviewed, and the advantages and problems
      associated with the current techniques are discussed. Particular emphasis is
      placed on its future directions, from both the technical and application sides. 

PMID- 25873341
TI  - Blocking the passage: C60 geometrically clogs K(+) channels.
AB  - Classical molecular dynamics (MD) simulations combined with docking calculations,
      potential of mean force estimates with the umbrella sampling method, and
      molecular mechanic/Poisson-Boltzmann surface area (MM-PBSA) energy calculations
      reveal that C60 may block K(+) channels with two mechanisms: a low affinity
      blockage from the extracellular side, and an open-channel block from the
      intracellular side. The presence of a low affinity binding-site at the
      extracellular entrance of the channel is in agreement with the experimental
      results showing a fast and reversible block without use-dependence, from the
      extracellular compartment. Our simulation protocol suggests the existence of
      another binding site for C60 located in the channel cavity at the intracellular
      entrance of the selectivity filter. The escape barrier from this binding site is
      ~21 kcal/mol making the corresponding kinetic rate of the order of minutes. The
      analysis of the change in solvent accessible surface area upon C60 binding shows
      that binding at this site is governed purely by shape complementarity, and that
      the molecular determinants of binding are conserved in the entire family of K(+)
      channels. The presence of this high-affinity binding site conserved among
      different K(+) channels may have serious implications for the toxicity of carbon
      nanomaterials. 

PMID- 25873342
TI  - Fluorine-modified bisbenzimide derivative as a molecular probe for bimodal and
      simultaneous detection of DNAs by (19)F NMR and fluorescence.
AB  - 3,5-Bis(trifluoromethyl)benzene modified bisbenzimide H 33258 was synthesized as
      a (19)F magnetic resonance-based DNA detection probe. The chemical shift and
      fluorescence of the probe were significantly changed by the addition of hairpin
      DNAs having an AATT sequence. The probe enables (19)F NMR/fluorescence bimodal
      detection of the model DNA double strands simultaneously. 

PMID- 25873343
TI  - Endostar combined with irinotecan/calcium folinate/5-fluorouracil (FOLFIRI) for
      treating advanced colorectal cancer: A clinical study.
AB  - PURPOSE: The current study aimed to evaluate the short-term efficacy and safety
      of endostar plus irinotecan/calcium folinate/5-fluorouracil (FOLFIRI) in
      treatment of advanced colorectal cancer (CRC). METHODS: Forty patients with
      advanced CRC were enrolled in this study and randomly assigned to two groups. The
      control group (n = 18) and tested group (n = 22) were received FOLFIRI alone and
      FOLFIRI plus endostar, respectively. The end points were overall response rate,
      progression-free survival (PFS) and toxicity. RESULTS: A total of 38 patients (17
      in control group and 21 in tested group) completed two cycles of treatment and
      were deemed assessable for response. Patients treated with FOLFIRI plus endostar
      experienced a obviously higher overall response rate (42.9%) compared with
      patients who received FOLFIRI alone (29.4%) and a statistically significant
      improvement in median PFS (14.5 vs. 11.0  months). The toxicity of
      FOLFIRI/endostar was comparative to that of FOLFIRI with regard to
      gastrointestinal reactions, haematologic toxicity, peripheral neuropathy and
      cholinergic syndrome. Cardiovascular adverse reactions including
      electrocardiogram abnormality and hypertension, which might be ascribed to
      endostar treatment, were reversible and manageable. CONCLUSION: The addition of
      endostar to FOLFIRI resulted in a higher overall response rate and longer PFS and
      did not increase unacceptable adverse responses in patients with advanced CRC.
      Future randomised controlled clinical trials with a larger group of patients are
      warranted to further investigate the value of FOLFIRI plus endostar in CRC
      treatment.

PMID- 25873344
TI  - Concise Review: Energy Metabolites: Key Mediators of the Epigenetic State of
      Pluripotency.
AB  - Recent studies suggest that the metabolic network is an important part of the
      molecular circuitry that underlies pluripotency. Of the metabolic pathways that
      were implicated in the pluripotency balance, "energy" metabolism is particularly
      notable. Its mechanism of action on pluripotency-regulating genes has been
      partially elucidated when three metabolites, namely acetate, S
      adenosylmethionine, and O-linked beta-N-acetylglucosamine were recently shown to
      link cytosolic signals to pluripotent gene expression. The cytosolic levels of
      these metabolites are the result of environmental perturbations, making them
      sensitive messengers, which are assumed to diffuse through the nuclear pores,
      being small molecules. Recent work also suggests that the modulation of the
      levels of these metabolites in pluripotent cells controls the balance between
      pluripotency and early commitment via epigenetic modifications. Here, we review
      recent studies that link metabolism and pluripotency via epigenetic modifications
      that occur through these three metabolites.

PMID- 25873345
TI  - Can healthy people benefit from health apps?

PMID- 25873346
TI  - Effects of high power ultrasound on all-E-beta-carotene, newly formed compounds
      analysis by ultra-high-performance liquid chromatography-tandem mass
      spectrometry.
AB  - To study effects of high power ultrasound treatment (20 kHz) on beta-carotene
      degradation, a second-order central composite design (CCD) was performed to
      investigate maximum beta-carotene loss with three independent factors (ultrasonic
      intensity, sonication time, and temperature). Results based on variance analysis
      and Pareto chart have shown that sonication time is the most important factor,
      followed by ultrasonic intensity level. The evolved degradation products have
      been tentatively identified using ultra high performance liquid chromatography
      coupled to both diode array detector and a mass spectrometer (UHPLC-DAD-MS). The
      main degradation products, tentatively identified, are three Z-isomers of beta
      carotene and seven beta-apo-carotenals/ones. Hypothesis on the degradation
      mechanism of carotenoids are presented.

PMID- 25873347
TI  - In colon cancer, normal colon tissue and blood cells have altered telomere
      lengths.
AB  - BACKGROUND: Telomere length (TL) shortened occurs in colorectal carcinogenetic
      process. Our objective is to determine if it is only a local fact or there are
      alterations in normal colon cells and in other body cells. METHODS: TL of tumoral
      and normal mucosa and leukocytes of 40 patients operated of colorectal cancer
      (CRC) and 40 control patients with normal colonoscopy were measured by Southern
      blot. Groups were matched by the same localization as tumors, sex, and age.
      RESULTS: In CRC patients, TRFL (Telomere Repeat Factor Length) leukocytes mean
      was 8.84 kpb, normal colonic mucosa 7.97 kpb, and tumoral mucosa 7.33 kpb (P <
      0.001). In the 40 normal control patients, mean TRFL of colonic mucosa was 7.76
      kpb, while in blood cells was 7.01 kpb (P < 0.001). We observed an inverse
      correlation between leukocytes TRFL and age (r(2)  = 0.17, P = 0.008). Mucosa
      TRFL correlates significantly with patient's age (r(2)  = 0.138, P = 0.018). TRFL
      of controls colonic mucosa correlates with TRFL of their blood cells (r(2)  =
      0.354, P < 0.001). CONCLUSIONS: Normal colonic mucosa and leukocytes in CCR
      patients presents telomere altered in respect to normal patients. Telomere length
      in normal leukocytes could be an initial marker for colorectal cancer.

PMID- 25873348
TI  - Aryl Hydrocarbon Receptor Activity of Tryptophan Metabolites in Young Adult Mouse
      Colonocytes.
AB  - The tryptophan microbiota metabolites indole-3-acetate, indole-3-aldehyde,
      indole, and tryptamine are aryl hydrocarbon receptor (AhR) ligands, and in this
      study we investigated their AhR agonist and antagonist activities in
      nontransformed young adult mouse colonocyte (YAMC) cells. Using Cyp1a1 mRNA as an
      Ah-responsive end point, we observed that the tryptophan metabolites were weak
      AhR agonists and partial antagonists in YAMC cells, and the pattern of activity
      was different from that previously observed in CaCo2 colon cancer cells. However,
      expansion of the end points to other Ah-responsive genes including the Cyp1b1,
      the AhR repressor (Ahrr), and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)
      inducible poly(ADP-ribose) polymerase (TiParp) revealed a highly complex pattern
      of AhR agonist/antagonist activities that were both ligand- and gene-dependent.
      For example, the magnitude of induction of Cyp1b1 mRNA was similar for TCDD,
      tryptamine, and indole-3-acetate, whereas lower induction was observed for indole
      and indole-3-aldehyde was inactive. These results suggest that the tryptophan
      metabolites identified in microbiota are selective AhR modulators.

PMID- 25873349
TI  - Effectiveness and feasibility of a software tool to help patients communicate
      with doctors about problems they face with their medication regimen (EMPATHy):
      study protocol for a randomized controlled trial.
AB  - BACKGROUND: Low-income, Mexican-American patients with diabetes exhibit high
      rates of medication nonadherence, poor blood sugar control and serious
      complications, and often have difficulty communicating their concerns about the
      medication regimen to physicians. Interventions led by community health workers,
      non-professional community members who are trained to work with patients to
      improve engagement and communication during the medical visit, have had mixed
      success in improving outcomes. The primary objective of this project is to pilot
      test a prototype software toolkit called "EMPATHy" that a community health worker
      can administer to help patients identify the most important barriers to adherence
      that they face and discuss these barriers with their doctor. METHODS/DESIGN: The
      EMPATHy toolkit will be piloted in an ongoing intervention (Coached Care) in
      which community health workers are trained to be "coaches" to meet with patients
      before the medical visit and help them prepare a list of important questions for
      the doctor. A total of 190 Mexican-American patients with poorly controlled type
      2 diabetes will be recruited from December 2014 through June 2015 and will be
      randomly assigned to complete either a single Coached Care intervention visit
      with no software tools or a Coached Care visit incorporating the EMPATHy software
      toolkit. The primary endpoints are (1) the development of a "contextualized plan
      of care" (i.e., a plan of care that addresses a barrier to medication adherence
      in the patient's daily life) with the doctor, determined from an audio recording
      of the medical visit, and (2) attainment of a concrete behavioral goal set during
      the intervention session, assessed in a 2-week follow-up phone call to the
      patient. The statistical analysis will include logistic regression models and is
      powered to detect a 50% increase in the primary endpoints. DISCUSSION: The study
      will provide evidence regarding the effectiveness and feasibility of a software
      tool to help patients communicate with doctors about problems they face with
      their medications. TRIAL REGISTRATION: ClinicalTrials.gov NCT02324036 Registered
      16 December 2014.

PMID- 25873351
TI  - mRNA and microRNA expression profiles of radioresistant NCI-H520 non-small cell
      lung cancer cells.
AB  - To elucidate the mechanism of radioresistance in non-small cell lung cancer
      (NSCLC) cells and to identify key molecules conferring radioresistance, the
      radioresistant subclone NCI-H520/R, derived from the NCI-H520 NSCLC cell line,
      was established with eight rounds of sublethal irradiation. The radioresistant
      features were subsequently assessed using a clonogenic assay, analysis of
      apoptosis and an MTT assay, the gene expression levels were examined using an
      Agilent Whole Human Genome 4 x 44 k Oligo microarray and Agilent Human
      miRCURY(TM) LNA array, and confirmed by reverse transcription-quantitative
      polymerase chain reaction. Pathway analysis and Gene Ontology (GO) analysis were
      performed to determine the biological functions of the subset of differentially
      expressed genes. miRNA-mRNA correlation analysis between the expression levels of
      each miRNA and all its predicted target genes was performed to further understand
      the radioresistance in the NCI-H520 cells. Following eight rounds of sublethal
      irradiation, a total of 2,862 mRNAs were significantly differentially expressed
      in the NCI-H520/R cells, including 893 upregulated genes and 1,969 downregulated
      genes. A total of 162 upregulated miRNAs and 274 downregulated miRNAs were
      significantly deregulated in the NCI-H520/R cells. Multiple core regulatory
      processes and signaling pathways were identified as being of likely relevance to
      radioresistance in NCI-H520/R cells, including the mitogen-activated protein
      kinase signaling pathway and neurotrophin signaling pathway. The expression of
      genes associated with radioresistance reflects the complex biological processes
      involved in clinical cancer cell eradication and requires further investigation
      for future enhancement of therapy.

PMID- 25873352
TI  - Dickkopf-1 induces apoptosis in the JEG3 and BeWo trophoblast tumor cell lines
      through the mitochondrial apoptosis pathway.
AB  - Gestational choriocarcinoma is a high-grade malignant tumor. In this study, the
      effects of Dickkopf-1 (DKK1) on a human trophoblast cell line was examined by
      using both in vitro and in vivo assays. DKK1 was observed to induce apoptosis and
      inhibit proliferation in JEG3 and BeWo cells. Moreover, DKK1 suppressed tumor
      growth in established xenograft tumor models. In western blot assays, DKK1 was
      found to inhibit the Wnt/beta-catenin signaling pathway and active the
      mitochondrial apoptosis pathway. Overall, our study demonstrated the antitumor
      activity of DKK1 towards the JEG3 and BeWo cells. Valuable insight into the
      mechanisms mediated by DKK1 was obtained, potentially leading to the
      identification of novel treatments for gestational choriocarcinoma.

PMID- 25873353
TI  - Thrombocytopenia associated with Mycoplasma pneumonia during pregnancy: case
      presentation and approach for differential diagnosis.
AB  - Thrombocytopenia during pregnancy has many different causes, but Mycoplasma
      pneumoniae is not usually considered one of the several pathogens that induce
      thrombocytopenia. Herein, we present a case of severe thrombocytopenia that was
      associated with M. pneumoniae during pregnancy. The patient experienced fever,
      cough, and cytopenia with M. pneumoniae-specific IgM antibody increasing from 40
      fold to 160-fold during the 2 weeks of illness. A diagnosis was made after
      excluding other diseases that cause thrombocytopenia. The patient was
      successfully treated with azithromycin hydrate, and she delivered a healthy
      newborn without any complications. Pregnant women who are infected with M.
      pneumoniae during pregnancy may develop severe and fatal thrombocytopenia. Prompt
      diagnosis and initiation of treatment lead to early recovery.

PMID- 25873355
TI  - Cognitive and Motivational Biases in Decision and Risk Analysis.
AB  - Behavioral decision research has demonstrated that judgments and decisions of
      ordinary people and experts are subject to numerous biases. Decision and risk
      analysis were designed to improve judgments and decisions and to overcome many of
      these biases. However, when eliciting model components and parameters from
      decisionmakers or experts, analysts often face the very biases they are trying to
      help overcome. When these inputs are biased they can seriously reduce the quality
      of the model and resulting analysis. Some of these biases are due to faulty
      cognitive processes; some are due to motivations for preferred analysis outcomes.
      This article identifies the cognitive and motivational biases that are relevant
      for decision and risk analysis because they can distort analysis inputs and are
      difficult to correct. We also review and provide guidance about the existing
      debiasing techniques to overcome these biases. In addition, we describe some
      biases that are less relevant because they can be corrected by using logic or
      decomposing the elicitation task. We conclude the article with an agenda for
      future research. 

PMID- 25873354
TI  - Shared genetic diversity across the global invasive range of the monk parakeet
      suggests a common restricted geographic origin and the possibility of convergent
      selection.
AB  - While genetic diversity is hypothesized to be an important factor explaining
      invasion success, there is no consensus yet on how variation in source
      populations or demographic processes affects invasiveness. We used mitochondrial
      DNA haplotypic and microsatellite genotypic data to investigate levels of genetic
      variation and reconstruct the history of replicate invasions on three continents
      in a globally invasive bird, the monk parakeet (Myiopsitta monachus). We
      evaluated whether genetic diversity at invasive sites could be explained by (i)
      the native source populations from which they were derived and (ii) demographic
      bottlenecks during introduction. Genetic data indicated a localized source area
      for most sampled invasive populations, with limited evidence for admixing of
      native source populations. This pattern largely coincides with historical data on
      pet trade exports. However, the invasive populations are genetically more similar
      than predicted from the export data alone. The extent of bottleneck effects
      varied among invasive populations. The observed low genetic diversity, evidence
      of demographic contraction and restricted source area do not support the
      hypothesis that invasion is favoured by the mixing and recombining of genetic
      variation from multiple source populations. Instead, they suggest that reduced
      genetic variation through random processes may not inhibit successful
      establishment and invasion in this species. However, convergent selection across
      invasive sites could also explain the observed patterns of reduction and
      similarity in genetic variation and/or the restricted source area. In general,
      the alternative explanation of intraspecific variation in invasive potential
      among genotypes or geographic areas is neglected, but warrants more attention as
      it could inform comparative studies and management of biological invaders.

PMID- 25873356
TI  - The cost of long-term follow-up of high-risk infants for research studies.
AB  - AIMS: Neonatal intensive care is expensive, and thus it is essential that its
      long-term outcomes are measured. The costs of follow-up studies for high-risk
      children who survive are unknown. This study aims to determine current costs for
      the assessment of health and development of children followed up in our research
      programme. METHODS: Costs were determined for children involved in the research
      follow-up programme at the Royal Women's Hospital, Melbourne, over the 6-month
      period between 1st January 2012 and 30th June 2012. The time required for health
      professionals involved in assessments in early and later childhood was estimated,
      and converted into dollar costs. Costs for equipment and data management were
      added. Estimated costs were compared with actual costs of running the research
      follow-up programme. RESULTS: A total of 134 children were assessed over the 6
      month period. The estimated average cost per child assessed was $1184, much
      higher than was expected. The estimated cost to assess a toddler was $1149,
      whereas for an 11-year-old it was $1443, the difference attributable to the
      longer psychological and paediatric assessments. The actual average cost per
      child assessed was $1623. The shortfall of $439 between the actual and estimated
      average costs per child arose chiefly because of the need to pay staff even when
      participants were late or failed to attend. CONCLUSIONS: The average costs of
      assessing children at each age for research studies are much higher than
      expected. These data are useful for planning similar long-term follow-up
      assessments for high-risk children.

PMID- 25873357
TI  - Making test results more easily understood by patients.

PMID- 25873358
TI  - Association between positive murine double minute 2 expression and
      clinicopathological characteristics of esophageal squamous cell carcinoma: a meta
      analysis.
AB  - The correlations of murine double minute 2 (MDM2) T309G and esophageal cancer
      were elucidated because the association between MDM2 expression states and
      clinicopathological parameters of esophageal squamous cell carcinoma (ESCC) is
      controversial. We conducted a meta-analysis on studies screened from PubMed, Web
      of Science, Embase, the Cochrane Library, and the Chinese Biomedical Literature
      Databases that were published before October 2014. All studies describing the
      association between MDM2 and ESCC were traced. Meta-analysis was performed using
      the STATA software (Stata Corp., College Station, TX, USA). A total of 9 studies
      with 707 cases and 324 controls were included. MDM2 expression was higher in ESCC
      than in normal esophageal epithelium (odds ratio [OR] 10.38, 95% confidence
      interval [CI] 6.42-16.78, P < 0.001). High MDM2 expression was associated with
      early primary tumor stage (T1/T2 vs. T3/T4, OR 0.59, 95% CI 0.38-0.92, P = 0.018)
      and increased risk of regional lymph node metastasis (N0 vs. N1, OR 1.66, 95% CI
      1.03-2.67, P = 0.039). However, no relationship was observed between MDM2
      expression and the risk of distant metastasis (OR = 2.09, 95% CI 1.00-4.36, P =
      0.050), and MDM2 was not significantly correlated with TP53 expression (OR 1.22,
      95% CI 0.53-2.77, P = 0.643). Our analysis suggests that MDM2 acts as a potent
      marker of early primary tumor stage but higher risk of regional lymph node
      metastasis in ESCC. However, because of the limited number of studies included,
      the result should be further clarified by well-designed prospective studies.

PMID- 25873359
TI  - Scaling of graphene integrated circuits.
AB  - The influence of transistor size reduction (scaling) on the speed of realistic
      multi-stage integrated circuits (ICs) represents the main performance metric of a
      given transistor technology. Despite extensive interest in graphene electronics,
      scaling efforts have so far focused on individual transistors rather than multi
      stage ICs. Here we study the scaling of graphene ICs based on transistors from
      3.3 to 0.5 MUm gate lengths and with different channel widths, access lengths,
      and lead thicknesses. The shortest gate delay of 31 ps per stage was obtained in
      sub-micron graphene ROs oscillating at 4.3 GHz, which is the highest oscillation
      frequency obtained in any strictly low-dimensional material to date. We also
      derived the fundamental Johnson limit, showing that scaled graphene ICs could be
      used at high frequencies in applications with small voltage swing. 

PMID- 25873360
TI  - How do patients with uveal melanoma experience and manage uncertainty? A
      qualitative study.
AB  - OBJECTIVES: Cancer survivors experience uncertainty about the future, which can
      be distressing. A prognostication tool is available for uveal melanoma survivors,
      which can provide accurate estimates of life expectancy - a key source of
      uncertainty. Accurate prognostic information has not previously been available
      for healthy cancer survivors. The aims of this study were to identify how
      patients experience prognostic information and how it affects their experience of
      uncertainty. METHODS: Semi-structured interviews were conducted with 25 healthy
      survivors of uveal melanoma 6-60 months after treatment (approximately 8-62
      months after receiving prognostic information). Data were analysed qualitatively.
      RESULTS: Patients did not feel that the prognostic information relieved
      uncertainty, which still overshadowed their lives. Different prognoses engendered
      different experiences of uncertainty. Those receiving poor life expectancy
      estimates reported uncertainties regarding the timing and form of metastases that
      they were likely to experience, but they also used uncertainty to justify feeling
      hopeful. Those receiving good prognoses were often unable wholly to accept these.
      Patients whose test results failed or were intermediate retained their original
      uncertainties. Patients managed their uncertainties by suppressing thoughts about
      them and by trusting in the care of clinicians and the health-care system.
      CONCLUSIONS: Uncertainty in the context of uveal melanoma is a complex and
      multifaceted experience that is not easily resolved by prognostication.
      Additional approaches are needed to help patients with the uncertainty that
      persists despite prognostication.

PMID- 25873361
TI  - In vitro study of platelet function confirms the contribution of the ultraviolet
      B (UVB) radiation in the lesions observed in riboflavin/UVB-treated platelet
      concentrates.
AB  - BACKGROUND: Platelet inactivation technologies (PITs) have been shown to increase
      platelet storage lesions (PSLs). This study investigates amotosalen/ultraviolet
      (UV)A- and riboflavin/UVB-induced platelet (PLT) lesions in vitro. Particular
      attention is given to the effect of UVB alone on PLTs. STUDY DESIGN AND METHODS:
      Buffy coat-derived PLT concentrates (PCs) were treated with amotosalen/UVA,
      riboflavin/UVB, or UVB alone and compared to untreated PCs throughout storage. In
      vitro PLT function was assessed by blood gas and metabolite analyses, flow
      cytometry-based assays (CD62P, JC-1, annexin V, PAC-1), hypotonic shock response,
      and static adhesion to fibrinogen-coated wells. RESULTS: In our experimental
      conditions, riboflavin/UVB-treated PCs showed the most pronounced differences
      compared to untreated and amotosalen/UVA-treated PCs. The riboflavin/UVB
      treatment led to a significant increase of anaerobic glycolysis rate despite
      functional mitochondria, a significant increase of CD62P on Day 2, and a decrease
      of JC-1 aggregates and increase of annexin V on Day 7. The expression of active
      GPIIbIIIa (PAC-1) and the adhesion to fibrinogen was significantly increased from
      Day 2 of storage in riboflavin/UVB-treated PCs. Importantly, we showed that these
      lesions were caused by the UVB radiation alone, independently of the presence of
      riboflavin. CONCLUSION: The amotosalen/UVA-treated PCs confirmed previously
      published results with a slight increase of PSLs compared to untreated PCs.
      Riboflavin/UVB-treated PCs present significant in vitro PSLs compared to
      untreated PCs. These lesions are caused by the UVB radiation alone and probably
      involve the generation of reactive oxygen species. The impact of these
      observations on clinical use must be investigated.

PMID- 25873362
TI  - Replication and extension of a check-in procedure to increase activity engagement
      among people with severe dementia.
AB  - Engelman, Altus, and Mathews (1999) evaluated a procedure to ensure that staff
      checked in with elderly residents in a nursing home and offered activity choices.
      We report findings of a replication, with some additional components, to increase
      appropriate activity engagement among 5 residents (aged 77 to 83 years) with
      severe dementia. Evaluated in a concurrent multiple baseline design across
      participants that incorporated partial withdrawal phases, activity engagement
      increased for 3 participants, with modest improvement for 1 other participant.
      The 4 responders all engaged in a wider variety of activities during
      intervention. 

PMID- 25873363
TI  - Targeted Histone Peptides: Insights into the Spatial Regulation of the
      Methyltransferase PRC2 by using a Surrogate of Heterotypic Chromatin.
AB  - Eukaryotic genomes are dynamically regulated through a host of epigenetic
      stimuli. The substrate for these epigenetic transactions, chromatin, is a polymer
      of nucleosome building blocks. In native chromatin, each nucleosome can differ
      from its neighbors as a result of covalent modifications to both the DNA and the
      histone packaging proteins. The heterotypic nature of chromatin presents a
      formidable obstacle to biochemical studies seeking to understand the role of
      context on epigenetic regulation. A chemical approach to the production of
      heterotypic chromatin that can be used in such studies is introduced. This method
      involves the attachment of a user-defined modified histone peptide to a
      designated nucleosome within the polymer by using a peptide nucleic acid (PNA)
      targeting compound. This strategy was applied to dissect the effect of chromatin
      context on the activity of the histone methyltransferase PRC2. The results show
      that PRC2 can be stimulated to produce histone H3 methylation from a defined
      nucleation site. 

PMID- 25873364
TI  - Gender-specific association between urinary sodium excretion and body
      composition: Analysis of the 2008-2010 Korean National Health and Nutrition
      Examination Surveys.
AB  - OBJECTIVE: Few studies have reported the relationship between sarcopenia and the
      estimated amount of sodium excreted in 24 h, as measured by the spot urine test
      (E24UNA), in a community-dwelling cohort. We investigated the gender specific
      association between E24UNA values and body composition indices. MATERIALS AND
      METHODS: Data from a total of 7162 participants (3545 men and 3617 postmenopausal
      women) aged 45 years or older were obtained from multiple Korea National Health
      and Nutrition Examination Surveys (2008-2010) and analyzed. The total amount of
      sodium excreted in the urine in a 24-h period was estimated with spot urine
      specimens. Sarcopenia was defined as an appendicular skeletal muscle mass divided
      by body weight (ASM/Wt) that was less than 1 standard deviation below the sex
      specific mean for young adults. RESULTS: E24UNA values were positively correlated
      with body mass index, waist circumference, total fat mass, and blood pressure; in
      contrast, E24UNA values were negatively correlated with ASM/Wt in both sexes.
      Compared with those in the lowest E24UNA tertile, participants in the highest
      E24UNA tertile were at higher risk for sarcopenia (men: odds ratio (OR)=1.3 [95%
      confidence interval (CI)=1.07-1.59]; women: OR=1.41 [95% CI=1.16-1.73]). Further
      classification of subjects with sarcopenia into sarcopenic obese and sarcopenic
      nonobese groups revealed that the highest E24UNA values were found in the
      sarcopenic obese group; this difference was statistically significant. The next
      highest levels were found in the sarcopenic nonobese group, followed by the
      nonsarcopenic group. This trend was observed in both sexes. CONCLUSION: High
      E24UNA values were independently associated with both sarcopenia and obesity in
      Korean individuals older than 45 years. These results suggest that high salt
      intake may have a deleterious effect on body composition.

PMID- 25873365
TI  - Psoriasis during pregnancy: characteristics and important management
      recommendations.
AB  - The treatment of psoriasis in pregnant women can be challenging. Psoriasis
      generally improves during pregnancy; however, many pregnant patients still
      require treatment. In treating pregnant patients, the benefits of treatment and
      risks to the mother and the fetus must be considered. For localized psoriasis,
      topical corticosteroids are the treatment of choice. Other topical agents that
      are approved for the treatment of psoriasis, such as topical tar products and
      topical tazarotene, should be avoided during pregnancy because of unclear risks
      of teratogenicity. For moderate-to-severe psoriasis, ultraviolet B phototherapy
      is preferred. Despite limited safety data, biologics are favored over other
      systemic medications when needed. While there are new treatment options for
      psoriasis, there is limited information on the safety of medications during
      pregnancy. 

PMID- 25873366
TI  - Efficacy of Gutta-Percha and Polytetrafluoroethylene Tape to Microbiologically
      Seal the Screw Access Channel of Different Prosthetic Implant Abutments.
AB  - PURPOSE: To evaluate in vitro, the efficacy of gutta-percha (GP) and
      polytetrafluoroethylene (PTFE) tape to act as a seal against the penetration of
      Escherichia coli through prosthetic implant abutments (PIA) with external hexagon
      (EH) and morse taper (MT) connections. MATERIALS AND METHODS: 120 sets of implant
      analogs with their respective PIA were used. 60 sets from each system were
      divided into four groups (n = 15): I - GP sealing; II - PTFE tape sealing; III -
      no sealing (NS) and IV - negative control. Microbiological challenge was
      performed by placing bacterial colonies inside the titanium PIA before screwing
      them into their respective analogs. Each set was immersed in 5 mL of BHI and
      incubated for 14 days with daily checks for contamination, according to the
      nutrient medium turbidity. RESULTS: The type of seal used influenced microbial
      penetration at all evaluation times (p < 0.05). Compared to GP, PTFE led to an
      increase in turbidity and its effectiveness against microbial penetration was
      equivalent to group NS. When the sealing efficacy of each group was compared in
      terms of time, Cochran's Q test revealed that in the two groups sealed with PTFE,
      there was a progressive increase in the number of turbid nutrient media (p <
      0.0001), while in the group sealed with GP, this was only observed in the MT
      system (p = 0.0310). CONCLUSIONS: Sealing the PIA channel with GP was a
      significantly superior approach to sealing it with PTFE tape. PTFE tape or NS led
      to a progressive increase in microbiological leakage over time in PIA channels,
      however, this only occurred with GP in the MT system.

PMID- 25873368
TI  - LLPi: Liverpool Lung Project Risk Prediction Model for Lung Cancer Incidence.
AB  - Identification of high-risk individuals will facilitate early diagnosis, reduce
      overall costs, and also improve the current poor survival from lung cancer. The
      Liverpool Lung Project prospective cohort of 8,760 participants ages 45 to 79
      years, recruited between 1998 and 2008, was followed annually through the
      hospital episode statistics until January 31, 2013. Cox proportional hazards
      models were used to identify risk predictors of lung cancer incidence. C
      statistic was used to assess the discriminatory accuracy of the models. Models
      were internally validated using the bootstrap method. During mean follow-up of
      8.7 years, 237 participants developed lung cancer. Age [hazard ratio (HR), 1.04;
      95% confidence interval (CI), 1.02-1.06], male gender (HR, 1.48; 95% CI, 1.10
      1.98), smoking duration (HR, 1.04; 95% CI, 1.03-1.05), chronic obstructive
      pulmonary disease (HR, 2.43; 95% CI, 1.79-3.30), prior diagnosis of malignant
      tumor (HR, 2.84; 95% CI, 2.08-3.89), and early onset of family history of lung
      cancer (HR, 1.68; 95% CI, 1.04-2.72) were associated with the incidence of lung
      cancer. The LLPi risk model had a good calibration (goodness-of-fit chi(2) 7.58,
      P = 0.371). The apparent C-statistic was 0.852 (95% CI, 0.831-0.873) and the
      optimism-corrected bootstrap resampling C-statistic was 0.849 (95% CI, 0.829
      0.873). The LLPi risk model may assist in identifying individuals at high risk of
      developing lung cancer in population-based screening programs.

PMID- 25873367
TI  - Regulation of VDR Expression in Apc-Mutant Mice, Human Colon Cancers and
      Adenomas.
AB  - One variable that may affect the ability of vitamin D to reduce colon cancer risk
      is the expression of its high-affinity receptor, VDR. Here, we show that vitamin
      D does not reduce tumor formation in Apc(Delta14/+) mice and that VDR expression
      is lost in the majority of the colon tumor cells. The extent of VDR loss
      corresponded inversely to the level of beta-catenin nuclear localization and
      could be observed in early lesions composed of just a few crypts. Analysis of
      reported VDR regulators showed that the repressing class I histone deacetylases
      (HDAC) were significantly elevated in the tumors (up to 4-fold), whereas the VDR
      activating retinoid X receptors (RXR) were downregulated (~50%). Expression of
      the Slug repressor was also increased, but was found primarily in stromal cells.
      Analysis of epigenetically active compounds on colon cell lines and intestinal
      organoids showed that HDAC inhibitors were particularly adept at stimulating VDR
      expression. Treatment of tumor-bearing Apc(Delta14/+) mice with the HDAC
      inhibitor panobinostat increased VDR expression in the tumors and normal mucosa.
      The RXR agonist bexarotene failed to activate VDR expression, indicating that RXR
      ligands were not limiting. Analysis of human microarray data indicated that VDR
      mRNA is frequently downregulated in colon adenomas, which correlated positively
      with RXRA expression and inversely with HDAC 2 and 8 expression. Human adenomas
      showed variable VDR protein expression levels, both between and within individual
      lesions. Determining the mechanisms of VDR regulation in colon neoplasms may
      significantly enhance our ability to use vitamin D as a cancer prevention agent.

PMID- 25873369
TI  - Anti-Mullerian hormone concentrations in premenopausal women and breast cancer
      risk.
AB  - Laboratory models support an inverse association between anti-Mullerian hormone
      (AMH) and breast tumor development. Human studies are lacking; one study (N = 105
      cases, 204 controls) with prospectively collected serum reported the opposite-an
      approximate 10-fold increase in breast cancer risk comparing fourth with first
      quartile AMH levels. We investigated the relation between serum AMH levels and
      breast cancer risk in a case-control (N = 452 cases, 902 controls) study nested
      within the prospective Sister Study cohort of 50,884 women. At enrollment,
      participants were ages 35 to 54, premenopausal, and completed questionnaires on
      medical and family history, lifestyle factors, and demographics. AMH (ng/mL) was
      measured by ultrasensitive ELISA in serum collected at enrollment and log
      transformed for analysis. Multivariate conditional logistic regression was used
      to calculate ORs and 95% confidence intervals (CI) to account for matching on age
      and enrollment year. Mean age at enrollment was 46.8 years with an average 2.9
      years from blood draw to breast cancer diagnosis (SD = 1.9). AMH concentrations
      were below the limit of detection (0.003 ng/mL) for approximately 25% of samples.
      Compared with samples below the LOD, women with AMH >2.84 ng/mL (90th percentile
      among controls) had a 2-fold increase in breast cancer odds (OR, 2.25; 95% CI,
      1.26-4.02). For each 1-unit increase in lnAMH, overall breast cancer odds
      increased by 8% (OR, 1.08; 95% CI, 1.02-1.15) and odds of estrogen receptor
      positive, invasive disease increased by 15% (OR, 1.15; 95% CI, 1.05-1.25). Our
      findings demonstrate an overall positive relation between AMH and breast cancer.

PMID- 25873370
TI  - Randomized, Placebo-Controlled Trial of Green Tea Catechins for Prostate Cancer
      Prevention.
AB  - Preclinical, epidemiologic, and prior clinical trial data suggest that green tea
      catechins (GTC) may reduce prostate cancer risk. We conducted a placebo
      controlled, randomized clinical trial of Polyphenon E (PolyE), a proprietary
      mixture of GTCs, containing 400 mg (-)-epigallocatechin-3-gallate (EGCG) per day,
      in 97 men with high-grade prostatic intraepithelial neoplasia (HGPIN) and/or
      atypical small acinar proliferation (ASAP). The primary study endpoint was a
      comparison of the cumulative one-year prostate cancer rates on the two study
      arms. No differences in the number of prostate cancer cases were observed: 5 of
      49 (PolyE) versus 9 of 48 (placebo), P = 0.25. A secondary endpoint comparing the
      cumulative rate of prostate cancer plus ASAP among men with HGPIN without ASAP at
      baseline, revealed a decrease in this composite endpoint: 3 of 26 (PolyE) versus
      10 of 25 (placebo), P < 0.024. This finding was driven by a decrease in ASAP
      diagnoses on the Poly E (0/26) compared with the placebo arm (5/25). A decrease
      in serum prostate-specific antigen (PSA) was observed on the PolyE arm [-0.87
      ng/mL; 95% confidence intervals (CI), -1.66 to -0.09]. Adverse events related to
      the study agent did not significantly differ between the two study groups. Daily
      intake of a standardized, decaffeinated catechin mixture containing 400 mg EGCG
      per day for 1 year accumulated in plasma and was well tolerated but did not
      reduce the likelihood of prostate cancer in men with baseline HGPIN or ASAP.

PMID- 25873371
TI  - Phylogenomic identification of regulatory sequences in bacteria: an analysis of
      statistical power and an application to Borrelia burgdorferi sensu lato.
AB  - Phylogenomic footprinting is an approach for ab initio identification of genome
      wide regulatory elements in bacterial species based on sequence conservation. The
      statistical power of the phylogenomic approach depends on the degree of sequence
      conservation, the length of regulatory elements, and the level of phylogenetic
      divergence among genomes. Building on an earlier model, we propose a binomial
      model that uses synonymous tree lengths as neutral expectations for determining
      the statistical significance of conserved intergenic spacer (IGS) sequences.
      Simulations show that the binomial model is robust to variations in the value of
      evolutionary parameters, including base frequencies and the transition-to
      transversion ratio. We used the model to search for regulatory sequences in the
      Lyme disease species group (Borrelia burgdorferi sensu lato) using 23 genomes.
      The model indicates that the currently available set of Borrelia genomes would
      not yield regulatory sequences shorter than five bases, suggesting that genome
      sequences of additional B. burgdorferi sensu lato species are needed.
      Nevertheless, we show that previously known regulatory elements are indeed
      strongly conserved in sequence or structure across these Borrelia species.
      Further, we predict with sufficient confidence two new RpoS binding sites, 39
      promoters, 19 transcription terminators, 28 noncoding RNAs, and four sets of
      coregulated genes. These putative cis- and trans-regulatory elements suggest
      novel, Borrelia-specific mechanisms regulating the transition between the tick
      and host environments, a key adaptation and virulence mechanism of B.
      burgdorferi. Alignments of IGS sequences are available on BorreliaBase.org, an
      online database of orthologous open reading frame (ORF) and IGS sequences in
      Borrelia. IMPORTANCE: While bacterial genomes contain mostly protein-coding
      genes, they also house DNA sequences regulating the expression of these genes.
      Gene regulatory sequences tend to be conserved during evolution. By sequencing
      and comparing related genomes, one can therefore identify regulatory sequences in
      bacteria based on sequence conservation. Here, we describe a statistical
      framework by which one may determine how many genomes need to be sequenced and at
      what level of evolutionary relatedness in order to achieve a high level of
      statistical significance. We applied the framework to Borrelia burgdorferi, the
      Lyme disease agent, and identified a large number of candidate regulatory
      sequences, many of which are known to be involved in regulating the phase
      transition between the tick vector and mammalian hosts.

PMID- 25873372
TI  - Characterization and detection of a widely distributed gene cluster that predicts
      anaerobic choline utilization by human gut bacteria.
AB  - Elucidation of the molecular mechanisms underlying the human gut microbiota's
      effects on health and disease has been complicated by difficulties in linking
      metabolic functions associated with the gut community as a whole to individual
      microorganisms and activities. Anaerobic microbial choline metabolism, a disease
      associated metabolic pathway, exemplifies this challenge, as the specific human
      gut microorganisms responsible for this transformation have not yet been clearly
      identified. In this study, we established the link between a bacterial gene
      cluster, the choline utilization (cut) cluster, and anaerobic choline metabolism
      in human gut isolates by combining transcriptional, biochemical, bioinformatic,
      and cultivation-based approaches. Quantitative reverse transcription-PCR analysis
      and in vitro biochemical characterization of two cut gene products linked the
      entire cluster to growth on choline and supported a model for this pathway.
      Analyses of sequenced bacterial genomes revealed that the cut cluster is present
      in many human gut bacteria, is predictive of choline utilization in sequenced
      isolates, and is widely but discontinuously distributed across multiple bacterial
      phyla. Given that bacterial phylogeny is a poor marker for choline utilization,
      we were prompted to develop a degenerate PCR-based method for detecting the key
      functional gene choline TMA-lyase (cutC) in genomic and metagenomic DNA. Using
      this tool, we found that new choline-metabolizing gut isolates universally
      possessed cutC. We also demonstrated that this gene is widespread in stool
      metagenomic data sets. Overall, this work represents a crucial step toward
      understanding anaerobic choline metabolism in the human gut microbiota and
      underscores the importance of examining this microbial community from a function
      oriented perspective. IMPORTANCE: Anaerobic choline utilization is a bacterial
      metabolic activity that occurs in the human gut and is linked to multiple
      diseases. While bacterial genes responsible for choline fermentation (the cut
      gene cluster) have been recently identified, there has been no characterization
      of these genes in human gut isolates and microbial communities. In this work, we
      use multiple approaches to demonstrate that the pathway encoded by the cut genes
      is present and functional in a diverse range of human gut bacteria and is also
      widespread in stool metagenomes. We also developed a PCR-based strategy to detect
      a key functional gene (cutC) involved in this pathway and applied it to
      characterize newly isolated choline-utilizing strains. Both our analyses of the
      cut gene cluster and this molecular tool will aid efforts to further understand
      the role of choline metabolism in the human gut microbiota and its link to
      disease.

PMID- 25873373
TI  - Metabolic signatures of bacterial vaginosis.
AB  - Bacterial vaginosis (BV) is characterized by shifts in the vaginal microbiota
      from Lactobacillus dominant to a microbiota with diverse anaerobic bacteria. Few
      studies have linked specific metabolites with bacteria found in the human vagina.
      Here, we report dramatic differences in metabolite compositions and
      concentrations associated with BV using a global metabolomics approach. We
      further validated important metabolites using samples from a second cohort of
      women and a different platform to measure metabolites. In the primary study, we
      compared metabolite profiles in cervicovaginal lavage fluid from 40 women with BV
      and 20 women without BV. Vaginal bacterial representation was determined using
      broad-range PCR with pyrosequencing and concentrations of bacteria by
      quantitative PCR. We detected 279 named biochemicals; levels of 62% of
      metabolites were significantly different in women with BV. Unsupervised
      clustering of metabolites separated women with and without BV. Women with BV have
      metabolite profiles marked by lower concentrations of amino acids and dipeptides,
      concomitant with higher levels of amino acid catabolites and polyamines. Higher
      levels of the signaling eicosanoid 12-hydroxyeicosatetraenoic acid (12-HETE), a
      biomarker for inflammation, were noted in BV. Lactobacillus crispatus and
      Lactobacillus jensenii exhibited similar metabolite correlation patterns, which
      were distinct from correlation patterns exhibited by BV-associated bacteria.
      Several metabolites were significantly associated with clinical signs and
      symptoms (Amsel criteria) used to diagnose BV, and no metabolite was associated
      with all four clinical criteria. BV has strong metabolic signatures across
      multiple metabolic pathways, and these signatures are associated with the
      presence and concentrations of particular bacteria. IMPORTANCE: Bacterial
      vaginosis (BV) is a common but highly enigmatic condition that is associated with
      adverse outcomes for women and their neonates. Small molecule metabolites in the
      vagina may influence host physiology, affect microbial community composition, and
      impact risk of adverse health outcomes, but few studies have comprehensively
      studied the metabolomics profile of BV. Here, we used mass spectrometry to link
      specific metabolites with particular bacteria detected in the human vagina by
      PCR. BV was associated with strong metabolic signatures across multiple pathways
      affecting amino acid, carbohydrate, and lipid metabolism, highlighting the
      profound metabolic changes in BV. These signatures were associated with the
      presence and concentrations of particular vaginal bacteria, including some
      bacteria yet to be cultivated, thereby providing clues as to the microbial origin
      of many metabolites. Insights from this study provide opportunities for
      developing new diagnostic markers of BV and novel approaches for treatment or
      prevention of BV.

PMID- 25873374
TI  - Functional dynamics of the gut microbiome in elderly people during probiotic
      consumption.
AB  - A mechanistic understanding of the purported health benefits conferred by
      consumption of probiotic bacteria has been limited by our knowledge of the
      resident gut microbiota and its interaction with the host. Here, we detail the
      impact of a single-organism probiotic, Lactobacillus rhamnosus GG ATCC 53103
      (LGG), on the structure and functional dynamics (gene expression) of the gut
      microbiota in a study of 12 healthy individuals, 65 to 80 years old. The analysis
      revealed that while the overall community composition was stable as assessed by
      16S rRNA profiling, the transcriptional response of the gut microbiota was
      modulated by probiotic treatment. Comparison of transcriptional profiles based on
      taxonomic composition yielded three distinct transcriptome groups that displayed
      considerable differences in functional dynamics. The transcriptional profile of
      LGG in vivo was remarkably concordant across study subjects despite the
      considerable interindividual nature of the gut microbiota. However, we identified
      genes involved in flagellar motility, chemotaxis, and adhesion from
      Bifidobacterium and the dominant butyrate producers Roseburia and Eubacterium
      whose expression was increased during probiotic consumption, suggesting that LGG
      may promote interactions between key constituents of the microbiota and the host
      epithelium. These results provide evidence for the discrete functional effects
      imparted by a specific single-organism probiotic and challenge the prevailing
      notion that probiotics substantially modify the resident microbiota within
      nondiseased individuals in an appreciable fashion. IMPORTANCE: Probiotic bacteria
      have been used for over a century to promote digestive health. Many individuals
      report that probiotics alleviate a number of digestive issues, yet little
      evidence links how probiotic microbes influence human health. Here, we show how
      the resident microbes that inhabit the healthy human gut respond to a probiotic.
      The well-studied probiotic Lactobacillus rhamnosus GG ATCC 53103 (LGG) was
      administered in a clinical trial, and a suite of measurements of the resident
      microbes were taken to evaluate potential changes over the course of probiotic
      consumption. We found that LGG transiently enriches for functions to potentially
      promote anti-inflammatory pathways in the resident microbes.

PMID- 25873376
TI  - Comments on Fouchier's calculation of risk and elapsed time for escape of a
      laboratory-acquired infection from his laboratory.

PMID- 25873375
TI  - Efficiency of conditionally attenuated Salmonella enterica serovar Typhimurium in
      bacterium-mediated tumor therapy.
AB  - Increasing numbers of cancer cases generate a great urge for new treatment
      options. Applying bacteria like Salmonella enterica serovar Typhimurium for
      cancer therapy represents an intensively explored option. These bacteria have
      been shown not only to colonize solid tumors but also to exhibit an intrinsic
      antitumor effect. In addition, they could serve as tumor-targeting vectors for
      therapeutic molecules. However, the pathogenic S. Typhimurium strains used for
      tumor therapy need to be attenuated for safe application. Here,
      lipopolysaccharide (LPS) deletion mutants (DeltarfaL, DeltarfaG, DeltarfaH,
      DeltarfaD, DeltarfaP, and DeltamsbB mutants) of Salmonella were investigated for
      efficiency in tumor therapy. Of such variants, the DeltarfaD and DeltarfaG deep
      rough mutants exhibited the best tumor specificity and lowest pathogenicity.
      However, the intrinsic antitumor effect was found to be weak. To overcome this
      limitation, conditional attenuation was tested by complementing the mutants with
      an inducible arabinose promoter. The chromosomal integration of the respective
      LPS biosynthesis genes into the araBAD locus exhibited the best balance of
      attenuation and therapeutic benefit. Thus, the present study establishes a basis
      for the development of an applicably cancer therapeutic bacterium. IMPORTANCE:
      Cancer has become the second most frequent cause of death in industrialized
      countries. This and the drawbacks of routine therapies generate an urgent need
      for novel treatment options. Applying appropriately modified S. Typhimurium for
      therapy represents the major challenge of bacterium-mediated tumor therapy. In
      the present study, we demonstrated that Salmonella bacteria conditionally
      modified in their LPS phenotype exhibit a safe tumor-targeting phenotype.
      Moreover, they could represent a suitable vehicle to shuttle therapeutic
      compounds directly into cancerous tissue without harming the host.

PMID- 25873377
TI  - Insights into hydrocarbon formation by nitrogenase cofactor homologs.
AB  - The L-cluster is an all-iron homolog of nitrogenase cofactors. Driven by
      europium(II) diethylenetriaminepentaacetate [Eu(II)-DTPA], the isolated L-cluster
      is capable of ATP-independent reduction of CO and CN(-) to C1 to C4 and C1 to C6
      hydrocarbons, respectively. Compared to its cofactor homologs, the L-cluster
      generates considerably more CH4 from the reduction of CO and CN(-), which could
      be explained by the presence of a "free" Fe atom that is "unmasked" by
      homocitrate as an additional site for methanation. Moreover, the elevated CH4
      formation is accompanied by a decrease in the amount of longer hydrocarbons
      and/or the lengths of the hydrocarbon products, illustrating a competition
      between CH4 formation/release and C-C coupling/chain extension. These
      observations suggest the possibility of designing simpler synthetic clusters for
      hydrocarbon formation while establishing the L-cluster as a platform for
      mechanistic investigations of CO and CN(-) reduction without complications
      originating from the heterometal and homocitrate components. IMPORTANCE:
      Nitrogenase is a metalloenzyme that is highly complex in structure and uniquely
      versatile in function. It catalyzes two reactions that parallel two important
      industrial processes: the reduction of nitrogen to ammonia, which parallels the
      Haber-Bosch process in ammonia production, and the reduction of carbon monoxide
      to hydrocarbons, which parallels the Fischer-Tropsch process in fuel production.
      Thus, the significance of nitrogenase can be appreciated from the perspective of
      the useful products it generates: (i) ammonia, the "fixed" nitrogen that is
      essential for the existence of the entire human population; and (ii)
      hydrocarbons, the "recycled" carbon fuel that could be used to directly address
      the worldwide energy shortage. This article provides initial insights into the
      catalytic characteristics of various nitrogenase cofactors in hydrocarbon
      formation. The reported assay system provides a useful tool for mechanistic
      investigations of this reaction while suggesting the possibility of designing
      bioinspired catalysts based on nitrogenase cofactors.

PMID- 25873378
TI  - Phylogenomic analysis and predicted physiological role of the proton
      translocating NADH:quinone oxidoreductase (complex I) across bacteria.
AB  - The proton-translocating NADH:quinone oxidoreductase (complex I) is a
      multisubunit integral membrane enzyme found in the respiratory chains of both
      bacteria and eukaryotic organelles. Although much research has focused on the
      enzyme's central role in the mitochondrial respiratory chain, comparatively
      little is known about its role in the diverse energetic lifestyles of different
      bacteria. Here, we used a phylogenomic approach to better understand the
      distribution of complex I across bacteria, the evolution of this enzyme, and its
      potential roles in shaping the physiology of different bacterial groups. By
      surveying 970 representative bacterial genomes, we predict complex I to be
      present in ~50% of bacteria. While this includes bacteria with a wide range of
      energetic schemes, the presence of complex I is associated with specific
      lifestyles, including aerobic respiration and specific types of phototrophy
      (bacteria with only a type II reaction center). A phylogeny of bacterial complex
      I revealed five main clades of enzymes whose evolution is largely congruent with
      the evolution of the bacterial groups that encode complex I. A notable exception
      includes the gammaproteobacteria, whose members encode one of two distantly
      related complex I enzymes predicted to participate in different types of
      respiratory chains (aerobic versus anaerobic). Comparative genomic analyses
      suggest a broad role for complex I in reoxidizing NADH produced from various
      catabolic reactions, including the tricarboxylic acid (TCA) cycle and fatty acid
      beta-oxidation. Together, these findings suggest diverse roles for complex I
      across bacteria and highlight the importance of this enzyme in shaping diverse
      physiologies across the bacterial domain. IMPORTANCE: Living systems use
      conserved energy currencies, including a proton motive force (PMF), NADH, and
      ATP. The respiratory chain enzyme, complex I, connects these energy currencies by
      using NADH produced during nutrient breakdown to generate a PMF, which is
      subsequently used for ATP synthesis. Our goal is to better understand the role of
      complex I in bacteria, whose energetic diversity allows us to view its function
      in a range of biological contexts. We analyzed sequenced bacterial genomes to
      predict the presence, evolution, and function of complex I in bacteria. We
      identified five main classes of bacterial complex I and predict that different
      classes participate in different types of respiratory chains (aerobic and
      anaerobic). We also predict that complex I helps maintain a cellular redox state
      by reoxidizing NADH produced from central metabolism. Our findings suggest
      diverse roles for complex I in bacterial physiology, highlighting the need for
      future laboratory-based studies.

PMID- 25873379
TI  - Reply to "Comments on Fouchier's calculation of risk and elapsed time for escape
      of a laboratory-acquired infection from his laboratory".

PMID- 25873381
TI  - Changes in expression induced by Epstein-Barr Virus LMP1-CTAR1: potential role of
      bcl3.
AB  - The Epstein-Barr virus protein latent membrane protein 1 (LMP1) has two NF-kappaB
      activating domains within its intracellular carboxy terminus (carboxy-terminal
      activating region 1 [CTAR1] and CTAR2). LMP1-CTAR1 is required for B-lymphocyte
      transformation, is capable of transforming rodent fibroblasts, and uniquely
      activates phosphoinositol (PI3) kinase, the noncanonical NF-kappaB pathway, and
      expression of the epidermal growth factor receptor (EGFR). In this study, the
      effects of LMP1-CTAR1 on cellular gene expression were determined by high
      throughput sequencing. Additionally, the binding of bcl3 was determined using
      chromatin immunoprecipitation (ChIP) and sequencing. LMP1-CTAR1 induced few
      changes in transcription with more genes showing decreased expression. Ingenuity
      pathway analysis indicated significant enrichment for genes involved in cancer
      and cellular movement, survival, growth, and proliferation pathways. ChIP in
      combination with high-throughput sequencing (ChIP-Seq) identified bcl3 binding
      for more than 2,000 genes in LMP1-CTAR1-expressing cells with more than 90% of
      the peaks at genes detected within the probable promoter region. Only a small
      subset of the genes with significant changes in expression had corresponding
      peaks in the bcl3 ChIP. However, both NFKB2 and PI3 kinase were identified in the
      bcl3 ChIP. Additionally, many of the predicted upstream regulators for the
      changes in expression were identified in the bcl3 ChIP. Analysis of the proteins
      in the NF-kappaB pathway revealed many changes identified by the high-throughput
      RNA sequencing (RNA-Seq) and bcl3 ChIP that would likely activate noncanonical NF
      kappaB signaling and possibly inhibit canonical NF-kappaB signaling. These
      findings suggest that the two LMP1 signaling domains modulate their combined
      activity and that the bcl3 transcription factor is likely responsible for some of
      the unique effects of CTAR1 on cellular expression. IMPORTANCE: The Epstein-Barr
      virus protein latent membrane protein 1 (LMP1) has potent effects on cell growth.
      LMP1 has two regions, carboxy-terminal activating region 1 (CTAR1) and CTAR2,
      that distinctly activate NF-kappaB, a transcription factor complex involved in
      activation of important host genes. In this study, analysis of the effects on
      cellular gene expression revealed that CTAR1 significantly affected cellular
      expression in part through effects on a specific form of NF-kappaB. The data
      suggest that LMP1 can activate a distinct subset of host gene expression through
      its CTAR1 domain which in combination with other signaling effects induced by the
      CTAR2 domain likely affects cell movement, survival, and growth.

PMID- 25873380
TI  - Molecular mechanism of flocculation self-recognition in yeast and its role in
      mating and survival.
AB  - We studied the flocculation mechanism at the molecular level by determining the
      atomic structures of N-Flo1p and N-Lg-Flo1p in complex with their ligands. We
      show that they have similar ligand binding mechanisms but distinct carbohydrate
      specificities and affinities, which are determined by the compactness of the
      binding site. We characterized the glycans of Flo1p and their role in this
      binding process and demonstrate that glycan-glycan interactions significantly
      contribute to the cell-cell adhesion mechanism. Therefore, the extended
      flocculation mechanism is based on the self-interaction of Flo proteins and this
      interaction is established in two stages, involving both glycan-glycan and
      protein-glycan interactions. The crucial role of calcium in both types of
      interaction was demonstrated: Ca(2+) takes part in the binding of the
      carbohydrate to the protein, and the glycans aggregate only in the presence of
      Ca(2+). These results unify the generally accepted lectin hypothesis with the
      historically first-proposed "Ca(2+)-bridge" hypothesis. Additionally, a new role
      of cell flocculation is demonstrated; i.e., flocculation is linked to cell
      conjugation and mating, and survival chances consequently increase significantly
      by spore formation and by introduction of genetic variability. The role of Flo1p
      in mating was demonstrated by showing that mating efficiency is increased when
      cells flocculate and by differential transcriptome analysis of flocculating
      versus nonflocculating cells in a low-shear environment (microgravity). The
      results show that a multicellular clump (floc) provides a uniquely organized
      multicellular ultrastructure that provides a suitable microenvironment to induce
      and perform cell conjugation and mating. IMPORTANCE: Yeast cells can form
      multicellular clumps under adverse growth conditions that protect cells from
      harsh environmental stresses. The floc formation is based on the self-interaction
      of Flo proteins via an N-terminal PA14 lectin domain. We have focused on the
      flocculation mechanism and its role. We found that carbohydrate specificity and
      affinity are determined by the accessibility of the binding site of the Flo
      proteins where the external loops in the ligand-binding domains are involved in
      glycan recognition specificity. We demonstrated that, in addition to the Flo
      lectin-glycan interaction, glycan-glycan interactions also contribute
      significantly to cell-cell recognition and interaction. Additionally, we show
      that flocculation provides a uniquely organized multicellular ultrastructure that
      is suitable to induce and accomplish cell mating. Therefore, flocculation is an
      important mechanism to enhance long-term yeast survival.

PMID- 25873382
TI  - Meteorin is upregulated in reactive astrocytes and functions as a negative
      feedback effector in reactive gliosis.
AB  - Reactive gliosis is a glial response to a wide range of central nervous system
      insults, which results in cellular and molecular changes to resting glial cells.
      Despite its fundamental effect on neuropathologies, the identification and
      characterization of the molecular mechanisms underlying this process remain to be
      fully elucidated. The aim of the present study was to analyze the expression
      profile and functions of the astrocytic neurotrophic factor, meteorin, in the
      progression of reactive gliosis. A mouse model of photothrombotic ischemia, and a
      primary astrocyte culture were used in the present study. Reverse transcription
      quantitative polymerase chain reaction, western blotting and immunofluorescence
      staining were performed to examine the expression levels of meteorin and reactive
      gliosis markers. Increased expression levels of meteorin were observed in
      reactive astrocytes in a photothrombotic ischemia mouse model, as well as in
      cultured astrocytes, which were stimulated by transforming growth factor-beta1.
      Exogenous treatment of the astrocytes with meteorin did not induce janus kinase
      signal transducer and activator of transcription 3 signaling, however, silencing
      the expression of meteorin in the astrocytes resulted in an upregulation of
      reactive astrocyte markers, including glial fibrillary acidic protein and
      S100beta, indicating that endogenous meteorin is required for the maintenance of
      astrocytic homeostasis. These results suggested a novel role for meteorin as a
      negative feedback effector in reactive gliosis.

PMID- 25873383
TI  - Patterns of leisure-time physical activity using multivariate finite mixture
      modeling and cardiovascular risk factors in the Northern Manhattan Study.
AB  - PURPOSE: Physical activity is currently commonly summarized by simple composite
      scores of total activity, such as total metabolic equivalent score (METS),
      without further information about the many specific aspects of activities. We
      sought to identify more comprehensive physical activity patterns, and their
      association with cardiovascular disease risk factors. METHODS: The Northern
      Manhattan Study is a multiethnic cohort of stroke-free individuals.
      Questionnaires were used to capture multiple dimensions of leisure-time physical
      activity. Participants were grouped into METS categories and also into clusters
      by multivariate mixture modeling of activity frequency, duration, energy
      expenditure, and number of activity types. Associations between clusters and risk
      factors were assessed using chi(2) tests. RESULTS: Using data available in 3293
      participants, we identified six model-based clusters that were differentiated by
      frequency and diversity of activities, rather than activity duration. High
      activity clusters had lower prevalence of the risk factors compared with those
      with lower activity; associations with obesity and hypertension remained
      significant after adjusting for METS (P = .027, .043). METS and risk factors were
      not significantly associated after adjusting for the clusters. CONCLUSIONS: Data
      driven clustering method is a principled, generalizable approach to depict
      physical activity and form subgroups associated with cardiovascular risk factors
      independently of METS.

PMID- 25873384
TI  - Connecting the oxidation of soot to its redox cycling abilities.
AB  - Although it is known that soot particles are emitted in large quantities to the
      atmosphere, our understanding of their environmental effects is limited by our
      knowledge of how their composition is subsequently altered through atmospheric
      processing. Here we present an on-line mass spectrometric study of the changing
      chemical composition of hydrocarbon soot particles as they are oxidized by gas
      phase ozone, and we show that the surface-mediated loss rates of adsorbed
      polycyclic aromatic hydrocarbons in soot are directly connected to a significant
      increase in the particle redox cycling abilities. With redox cycling implicated
      as an oxidative stress mechanism that arises after inhalation of atmospheric
      particles, this work draws a quantitative connection between the detailed
      heterogeneous chemistry occurring on atmospheric particles and a potential toxic
      mechanism attributable to that aerosol. 

PMID- 25873385
TI  - Arabidopsis ROOT PHOTOTROPISM2 Contributes to the Adaptation to High-Intensity
      Light in Phototropic Responses.
AB  - Living organisms adapt to changing light environments via mechanisms that enhance
      photosensitivity under darkness and attenuate photosensitivity under bright light
      conditions. In hypocotyl phototropism, phototropin1 (phot1) blue light
      photoreceptors mediate both the pulse light-induced, first positive phototropism
      and the continuous light-induced, second positive phototropism, suggesting the
      existence of a mechanism that alters their photosensitivity. Here, we show that
      light induction of ROOT PHOTOTROPISM2 (RPT2) underlies photosensory adaptation in
      hypocotyl phototropism of Arabidopsis thaliana. rpt2 loss-of-function mutants
      exhibited increased photosensitivity to very low fluence blue light but were
      insensitive to low fluence blue light. Expression of RPT2 prior to phototropic
      stimulation in etiolated seedlings reduced photosensitivity during first positive
      phototropism and accelerated second positive phototropism. Our microscopy and
      biochemical analyses indicated that blue light irradiation causes
      dephosphorylation of NONPHOTOTROPIC HYPOCOTYL3 (NPH3) proteins and mediates their
      release from the plasma membrane. These phenomena correlate closely with the
      desensitization of phot1 signaling during the transition period from first
      positive phototropism to second positive phototropism. RPT2 modulated the
      phosphorylation of NPH3 and promoted reconstruction of the phot1-NPH3 complex on
      the plasma membrane. We conclude that photosensitivity is increased in the
      absence of RPT2 and that this results in the desensitization of phot1. Light
      mediated induction of RPT2 then reduces the photosensitivity of phot1, which is
      required for second positive phototropism under bright light conditions. 

PMID- 25873386
TI  - Exploiting Differential Gene Expression and Epistasis to Discover Candidate Genes
      for Drought-Associated QTLs in Arabidopsis thaliana.
AB  - Soil water availability represents one of the most important selective agents for
      plants in nature and the single greatest abiotic determinant of agricultural
      productivity, yet the genetic bases of drought acclimation responses remain
      poorly understood. Here, we developed a systems-genetic approach to characterize
      quantitative trait loci (QTLs), physiological traits and genes that affect
      responses to soil moisture deficit in the TSUxKAS mapping population of
      Arabidopsis thaliana. To determine the effects of candidate genes underlying
      QTLs, we analyzed gene expression as a covariate within the QTL model in an
      effort to mechanistically link markers, RNA expression, and the phenotype. This
      strategy produced ranked lists of candidate genes for several drought-associated
      traits, including water use efficiency, growth, abscisic acid concentration
      (ABA), and proline concentration. As a proof of concept, we recovered known
      causal loci for several QTLs. For other traits, including ABA, we identified
      novel loci not previously associated with drought. Furthermore, we documented
      natural variation at two key steps in proline metabolism and demonstrated that
      the mitochondrial genome differentially affects genomic QTLs to influence proline
      accumulation. These findings demonstrate that linking genome, transcriptome, and
      phenotype data holds great promise to extend the utility of genetic mapping, even
      when QTL effects are modest or complex. 

PMID- 25873387
TI  - The Solanum commersonii Genome Sequence Provides Insights into Adaptation to
      Stress Conditions and Genome Evolution of Wild Potato Relatives.
AB  - Here, we report the draft genome sequence of Solanum commersonii, which consists
      of ~830 megabases with an N50 of 44,303 bp anchored to 12 chromosomes, using the
      potato (Solanum tuberosum) genome sequence as a reference. Compared with potato,
      S. commersonii shows a striking reduction in heterozygosity (1.5% versus 53 to
      59%), and differences in genome sizes were mainly due to variations in intergenic
      sequence length. Gene annotation by ab initio prediction supported by RNA-seq
      data produced a catalog of 1703 predicted microRNAs, 18,882 long noncoding RNAs
      of which 20% are shown to target cold-responsive genes, and 39,290 protein-coding
      genes with a significant repertoire of nonredundant nucleotide binding site
      encoding genes and 126 cold-related genes that are lacking in S. tuberosum.
      Phylogenetic analyses indicate that domesticated potato and S. commersonii
      lineages diverged ~2.3 million years ago. Three duplication periods corresponding
      to genome enrichment for particular gene families related to response to salt
      stress, water transport, growth, and defense response were discovered. The draft
      genome sequence of S. commersonii substantially increases our understanding of
      the domesticated germplasm, facilitating translation of acquired knowledge into
      advances in crop stability in light of global climate and environmental changes. 

PMID- 25873388
TI  - Site-specific fluorescence spectrum detection and characterization of hASIC1a
      channels upon toxin mambalgin-1 binding in live mammalian cells.
AB  - The synthesis of fluorescent unnatural amino-acid Anap was optimized and the Anap
      was incorporated into four sites in an acid-pocket or a transmembrane region of
      human acid-sensing ion channel-1a (hASIC1a). Combinational Anap fluorescence
      spectra and patch-clamp electrophysiology data illustrated site-specific
      conformational responses upon toxin mambalgin-1 binding. This combinational
      approach can be used to analyse conformational properties of many different
      eukaryotic proteins in their functional states, in a site-specific manner in live
      mammalian cells. 

PMID- 25873389
TI  - Novel Interaction of Class IIb Histone Deacetylase 6 (HDAC6) with Class IIa HDAC9
      Controls Gonadotropin Releasing Hormone (GnRH) Neuronal Cell Survival and
      Movement.
AB  - The impact of histone deacetylases (HDACs) in the control of gonadotropin
      releasing hormone (GnRH) neuronal development is unknown. We identified an
      increase in many HDACs in GT1-7 (differentiated) compared with NLT
      (undifferentiated) GnRH neuronal cell lines. Increased HDAC9 mRNA and protein and
      specific deacetylase activity in GT1-7 cells suggested a functional role.
      Introduction of HDAC9 in NLT cells protected from serum withdrawal induced
      apoptosis and impaired basal neuronal cell movement. Conversely, silencing of
      endogenous HDAC9 in GT1-7 cells increased apoptosis and cell movement. Comparison
      of WT and mutant HDAC9 constructs demonstrated that the HDAC9 pro-survival
      effects required combined cytoplasmic and nuclear localization, whereas the
      effects on cell movement required a cytoplasmic site of action. Co
      immunoprecipitation demonstrated a novel interaction of HDAC9 selectively with
      the Class IIb HDAC6. HDAC6 was also up-regulated at the mRNA and protein levels,
      and HDAC6 catalytic activity was significantly increased in GT1-7 compared with
      NLT cells. HDAC9 interacted with HDAC6 through its second catalytic domain.
      Silencing of HDAC6, HDAC9, or both, in GT1-7 cells augmented apoptosis compared
      with controls. HDAC6 and -9 had additive effects to promote cell survival via
      modulating the BAX/BCL2 pathway. Silencing of HDAC6 resulted in an activation of
      movement of GT1-7 cells with induction in acetylation of alpha-tubulin.
      Inhibition of HDAC6 and HDAC9 together resulted in an additive effect to increase
      cell movement but did not alter the acetylation of alphatubulin. Together, these
      studies identify a novel interaction of Class IIa HDAC9 with Class IIb HDAC6 to
      modulate cell movement and survival in GnRH neurons. 

PMID- 25873390
TI  - Autocrine/Paracrine Human Growth Hormone-stimulated MicroRNA 96-182-183 Cluster
      Promotes Epithelial-Mesenchymal Transition and Invasion in Breast Cancer.
AB  - Human growth hormone (hGH) plays critical roles in pubertal mammary gland growth,
      development, and sexual maturation. Accumulated studies have reported that
      autocrine/paracrine hGH is an orthotopically expressed oncoprotein that promotes
      normal mammary epithelial cell oncogenic transformation. Autocrine/paracrine hGH
      has also been reported to promote mammary epithelial cell epithelial-mesenchymal
      transition (EMT) and invasion. However, the underlying mechanism remains largely
      obscure. MicroRNAs (miRNAs) are reported to be involved in regulation of multiple
      cellular functions of cancer. To determine whether autocrine/paracrine hGH
      promotes EMT and invasion through modulation of miRNA expression, we performed
      microarray profiling using MCF-7 cells stably expressing wild type or a
      translation-deficient hGH gene and identified miR-96-182-183 as an
      autocrine/paracrine hGH-regulated miRNA cluster. Forced expression of miR-96-182
      183 conferred on epithelioid MCF-7 cells a mesenchymal phenotype and promoted
      invasive behavior in vitro and dissemination in vivo. Moreover, we observed that
      miR-96-182-183 promoted EMT and invasion by directly and simultaneously
      suppressing BRMS1L (breast cancer metastasis suppressor 1-like) gene expression.
      miR-96 and miR-182 also targeted GHR, providing a potential negative feedback
      loop in the hGH-GHR signaling pathway. We further demonstrated that
      autocrine/paracrine hGH stimulated miR-96-182-183 expression and facilitated EMT
      and invasion via STAT3 and STAT5 signaling. Consistent with elevated expression
      of autocrine/paracrine hGH in metastatic breast cancer tissue, miR-96-182-183
      expression was also remarkably enhanced. Hence, we delineate the roles of the
      miRNA-96-182-183 cluster and elucidate a novel hGH-GHR-STAT3/STAT5-miR-96-182-183
      BRMS1L-ZEB1/E47-EMT/invasion axis, which provides further understanding of the
      mechanism of autocrine/paracrine hGH-stimulated EMT and invasion in breast
      cancer. 

PMID- 25873391
TI  - MicroRNA-155 Reinforces HIV Latency.
AB  - The presence of a small number of infected but transcriptionally dormant cells
      currently thwarts a cure for the more than 35 million individuals infected with
      HIV. Reactivation of these latently infected cells may result in three fates: 1)
      cell death due to a viral cytopathic effect, 2) cell death due to immune
      clearance, or 3) a retreat into latency. Uncovering the dynamics of HIV gene
      expression and silencing in the latent reservoir will be crucial for developing
      an HIV-1 cure. Here we identify and characterize an intracellular circuit
      involving TRIM32, an HIV activator, and miR-155, a microRNA that may promote a
      return to latency in these transiently activated reservoir cells. Notably, we
      demonstrate that TRIM32, an E3 ubiquitin ligase, promotes reactivation from
      latency by directly modifying IkappaBalpha, leading to a novel mechanism of NF
      kappaB induction not involving IkappaB kinase activation. 

PMID- 25873392
TI  - The tRNA A76 Hydroxyl Groups Control Partitioning of the tRNA-dependent Pre- and
      Post-transfer Editing Pathways in Class I tRNA Synthetase.
AB  - Aminoacyl-tRNA synthetases catalyze ATP-dependent covalent coupling of cognate
      amino acids and tRNAs for ribosomal protein synthesis. Escherichia coli isoleucyl
      tRNA synthetase (IleRS) exploits both the tRNA-dependent pre- and post-transfer
      editing pathways to minimize errors in translation. However, the molecular
      mechanisms by which tRNA(Ile) organizes the synthetic site to enhance pre
      transfer editing, an idiosyncratic feature of IleRS, remains elusive. Here we
      show that tRNA(Ile) affects both the synthetic and editing reactions localized
      within the IleRS synthetic site. In a complex with cognate tRNA, IleRS exhibits a
      10-fold faster aminoacyl-AMP hydrolysis and a 10-fold drop in amino acid affinity
      relative to the free enzyme. Remarkably, the specificity against non-cognate
      valine was not improved by the presence of tRNA in either of these processes.
      Instead, amino acid specificity is determined by the protein component per se,
      whereas the tRNA promotes catalytic performance of the synthetic site, bringing
      about less error-prone and kinetically optimized isoleucyl-tRNA(Ile) synthesis
      under cellular conditions. Finally, the extent to which tRNA(Ile) modulates
      activation and pre-transfer editing is independent of the intactness of its 3'
      end. This finding decouples aminoacylation and pre-transfer editing within the
      IleRS synthetic site and further demonstrates that the A76 hydroxyl groups
      participate in post-transfer editing only. The data are consistent with a model
      whereby the 3'-end of the tRNA remains free to sample different positions within
      the IleRS.tRNA complex, whereas the fine-tuning of the synthetic site is attained
      via conformational rearrangement of the enzyme through the interactions with the
      remaining parts of the tRNA body. 

PMID- 25873393
TI  - Subtle Change in the Charge Distribution of Surface Residues May Affect the
      Secondary Functions of Cytochrome c.
AB  - Although the primary function of cytochrome c (cyt c) is electron transfer, the
      protein caries out an additional secondary function involving its interaction
      with membrane cardiolipin (CDL), its peroxidase activity, and the initiation of
      apoptosis. Whereas the primary function of cyt c is essentially conserved, its
      secondary function varies depending on the source of the protein. We report here
      a detailed experimental and computational study, which aims to understand, at the
      molecular level, the difference in the secondary functions of cyt c obtained from
      horse heart (mammalian) and Saccharomyces cerevisiae (yeast). The conformational
      landscape of cyt c has been found to be heterogeneous, consisting of an
      equilibrium between the compact and extended conformers as well as the oligomeric
      species. Because the determination of relative populations of these conformers is
      difficult to obtain by ensemble measurements, we used fluorescence correlation
      spectroscopy (FCS), a method that offers single-molecule resolution. The
      population of different species is found to depend on multiple factors, including
      the protein source, the presence of CDL and urea, and their concentrations. The
      complex interplay between the conformational distribution and oligomerization
      plays a crucial role in the variation of the pre-apoptotic regulation of cyt c
      observed from different sources. Finally, computational studies reveal that the
      variation in the charge distribution at the surface and the charge reversal sites
      may be the key determinant of the conformational stability of cyt c. 

PMID- 25873394
TI  - Phosphatase and Tensin Homolog (PTEN) Represses Colon Cancer Progression through
      Inhibiting Paxillin Transcription via PI3K/AKT/NF-kappaB Pathway.
AB  - The tumor suppressor gene phosphatase and tensin homolog (PTEN) is frequently
      mutated in colon cancer. However, the potential contribution of loss of PTEN to
      colon cancer progression remains unclear. In this study, we demonstrated that
      PTEN overexpression or knockdown in Lovo colon cancer cells decreased or
      increased paxillin expression, respectively. Moreover, paxillin reversed PTEN
      mediated inhibition of Lovo cell invasion and migration. Overexpression of PTEN
      in an orthotropic colon cancer nude mice model inhibited tumor formation and
      progression. In addition, PTEN protein level was negatively correlated with that
      of paxillin in human colon cancer tissues. Mechanistically, we identified three
      NF-kappaB binding sites on paxillin promoter and confirmed that paxillin was a
      direct transcriptional target of NF-kappaB. Our findings reveal a novel mechanism
      by which PTEN inhibits the progression of colon cancer by inhibiting paxillin
      expression downstream of PI3K/AKT/NF-kappaB pathway. Thereby, PTEN/PI3K/AKT/NF
      kappaB/paxillin signaling cascade is an attractive therapeutic target for colon
      cancer progression. 

PMID- 25873395
TI  - Evidence for Two Distinct Binding Sites for Lipoprotein Lipase on
      Glycosylphosphatidylinositol-anchored High Density Lipoprotein-binding Protein 1
      (GPIHBP1).
AB  - GPIHBP1 is an endothelial membrane protein that transports lipoprotein lipase
      (LPL) from the subendothelial space to the luminal side of the capillary
      endothelium. Here, we provide evidence that two regions of GPIHBP1, the acidic N
      terminal domain and the central Ly6 domain, interact with LPL as two distinct
      binding sites. This conclusion is based on comparative binding studies performed
      with a peptide corresponding to the N-terminal domain of GPIHBP1, the Ly6 domain
      of GPIHBP1, wild type GPIHBP1, and the Ly6 domain mutant GPIHBP1 Q114P. Although
      LPL and the N-terminal domain formed a tight but short lived complex,
      characterized by fast on- and off-rates, the complex between LPL and the Ly6
      domain formed more slowly and persisted for a longer time. Unlike the interaction
      of LPL with the Ly6 domain, the interaction of LPL with the N-terminal domain was
      significantly weakened by salt. The Q114P mutant bound LPL similarly to the N
      terminal domain of GPIHBP1. Heparin dissociated LPL from the N-terminal domain,
      and partially from wild type GPIHBP1, but was unable to elute the enzyme from the
      Ly6 domain. When LPL was in complex with the acidic peptide corresponding to the
      N-terminal domain of GPIHBP1, the enzyme retained its affinity for the Ly6
      domain. Furthermore, LPL that was bound to the N-terminal domain interacted with
      lipoproteins, whereas LPL bound to the Ly6 domain did not. In summary, our data
      suggest that the two domains of GPIHBP1 interact independently with LPL and that
      the functionality of LPL depends on its localization on GPIHBP1. 

PMID- 25873396
TI  - Pathogenesis of selective insulin resistance in isolated hepatocytes.
AB  - The development of insulin resistance (IR) in the liver is a key pathophysiologic
      event in the development of type 2 diabetes. Although insulin loses its ability
      to suppress glucose production, it largely retains its capacity to drive
      lipogenesis. This selective IR results in the characteristic hyperglycemia and
      dyslipidemia of type 2 diabetes. The delineation of two branched pathways of
      insulin receptor (InsR) signaling to glucose versus triglyceride production, one
      through FoxO and the other through SREBP-1c, provides a mechanism to account for
      this pathophysiological abnormality. We tested the complementary hypothesis that
      selective IR arises due to different intrinsic sensitivities of glucose
      production versus de novo lipogenesis to insulin as a result of cell-autonomous
      down-regulation of InsR number in response to chronic hyperinsulinemia. We
      demonstrate in mouse primary hepatocytes that chronic hyperinsulinemia abrogates
      insulin's inhibition of glucose production, but not its stimulation of de novo
      lipogenesis. Using a competitive inhibitor of InsR, we show that there is a 4
      fold difference between levels of InsR inhibition required to cause resistance of
      glucose production versus lipogenesis to the actions of insulin. Our data support
      a parsimonious model in which differential InsR activation underlies the
      selective IR of glucose production relative to lipogenesis, but both processes
      require signaling through Akt1/2. 

PMID- 25873397
TI  - Cyclic AMP Response Element-binding Protein H (CREBH) Mediates the Inhibitory
      Actions of Tumor Necrosis Factor alpha in Osteoblast Differentiation by
      Stimulating Smad1 Degradation.
AB  - Endoplasmic reticulum (ER) stress transducers, such as old astrocyte specifically
      induced substance (OASIS) and activating transcription factor 6 (ATF6), which are
      induced by bone morphogenetic protein 2 (BMP2), regulate bone formation and
      osteoblast differentiation. Here, we examined the role of cAMP response element
      binding protein H (CREBH), a member of the same family of ER membrane-bound basic
      leucine zipper (bZIP) transcription factors as OASIS and ATF6, in osteoblast
      differentiation and bone formation. Proinflammatory cytokine TNFalpha increased
      CREBH expression by up-regulating the nuclear factor-kappaB (NF-kappaB) signaling
      pathway in osteoblasts, increased the level of N-terminal fragment of CREBH in
      the nucleus, and inhibited BMP2 induction of osteoblast specific gene expression.
      Overexpression of CREBH suppressed BMP2-induced up-regulation of the osteogenic
      markers runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP),
      and osteocalcin (OC) in MC3T3-E1 cells and primary osteoblasts, as well as BMP2
      induced ALP activity and OC protein production. In contrast, knockdown of CREBH
      attenuated the inhibitory effect of TNFalpha on BMP2-induced osteoblast
      differentiation. Mechanistic studies revealed that CREBH increased the expression
      of Smad ubiquitination regulatory factor 1 (Smurf1), leading to ubiquitin
      dependent degradation of Smad1, whereas knockdown of CREBH inhibited TNFalpha
      mediated degradation of Smad1 by Smurf1. Consistent with these in vitro findings,
      administration of Ad-CREBH inhibited BMP2-induced ectopic and orthotopic bone
      formation in vivo. Taken together, these results suggest that CREBH is a novel
      negative regulator of osteoblast differentiation and bone formation. 

PMID- 25873398
TI  - National Trends and Factors Associated with Hospital Costs Following Thyroid
      Surgery.
AB  - BACKGROUND: Medical costs in the United States have been increasing
      disproportionally to gross domestic product, raising concerns about the
      sustainability of U.S. healthcare expenditures. Care of patients with thyroid
      disease has been identified as an area of medicine where cost increases have been
      pronounced. OBJECTIVES: The goals of this study were to identify potential
      drivers of the cost of hospitalization following thyroid surgery, and to
      understand which of these factors may be contributing to observed increases in
      cost from 2003 to 2011. METHODS: A retrospective cross-sectional analysis of
      discharge data from the Nationwide Inpatient Sample (NIS) database for all
      admissions following thyroid lobectomy or total thyroidectomy in the years 2003,
      2007, and 2011 was performed. Multiple regression analysis via a weighted
      generalized linear model was used to identify factors that were independently
      associated with high cost of hospitalization. Trend as well as subgroup analyses
      were then performed to identify which of these factors could be contributing to
      increasing costs. RESULTS: There were 47,854 hospital admissions following total
      thyroidectomy or thyroid lobectomy identified in the years 2003, 2007, and 2011.
      The aggregate national cost of hospitalization increased from $198 million in
      2003 to $373 million in 2011 in inflation-adjusted 2011 dollars. The weighted
      mean cost of hospitalization following thyroid surgery increased from $6154 to
      $8982 from 2003 to 2011 in inflation-adjusted 2011 dollars. Higher comorbidity
      score, total thyroidectomy, lymphadenectomy, western region, rural region, and
      certain postoperative complications were the factors most highly associated with
      increased hospital costs. Of these, an increasing proportion of patients with
      higher severity of illness score and an increasing proportion of patients
      undergoing total thyroidectomy and lymphadenectomy were implicated as the most
      likely contributors to the cost increases. The rate of total thyroidectomy and
      lymphadenectomy was found to be increasing for patients with both benign and
      malignant thyroid disease. CONCLUSIONS: According to the NIS data set, costs
      associated with hospitalization after thyroid surgery increased markedly from
      2003 to 2011. This increase could be in part due to a growing proportion of
      sicker patients undergoing more extensive surgery, but a number of confounders in
      this study limit the conclusions. Further analysis of factors that could be
      associated with the rising costs of inpatient thyroid surgery should be
      undertaken.

PMID- 25873399
TI  - Inpatient management of gout in a New Zealand hospital: a retrospective audit.
AB  - AIM: To review inpatient management of acute gout in a New Zealand hospital.
      METHODS: A retrospective file review of all acute episodes of gout at Hutt
      Hospital, Wellington, New Zealand over a 1 year period. RESULTS: In the course of
      a year, there were 90 admissions for, or complicated by, acute gout. In 31 cases,
      gout was the primary diagnosis. Median length of stay was 5 days and readmissions
      were common. The majority of patients (87%) were known to have gout before
      admission, yet only 50% of these patients were on uric acid lowering treatment.
      Serum urate was measured in only 60% of patients with a mean level of 0.471
      mmol/L. Treatment for the acute attack was evenly split between monotherapy (49%)
      and polytherapy (49%). Treatment modalities used were: prednisone (61%), non
      steroidal anti-inflammatories (40%), colchicine (40%), adrenocorticotrophic
      hormone (ACTH) (15%) and intrarticular steroids (7%). Patients were generally
      treated in a timely manner with few patients experiencing delays. Patients seen
      by the Rheumatology Department were more likely to receive polytherapy, be
      treated with intra-articular steroids or ACTH and to start allopurinol. The
      'treat-to-target' approach to the management of elevated serum urate was
      mentioned in only 9% of cases. CONCLUSION: There was considerable variability in
      the investigation and management of acute gout, with significant deviation from
      published protocols. The 'treat-to-target' approach to the management of elevated
      urate has not yet been widely adopted by the physicians in this New Zealand
      hospital.

PMID- 25873400
TI  - Seamless Rim-Functionalization of h-BN with Silica-Experiment and Theoretical
      Modeling.
AB  - Boron nitride contains six-ring layers, which are isostructural to graphene, and
      it exhibits similar extraordinary mechanical strength. Unlike graphene, hexagonal
      boron nitride (h-BN) is an insulator and has some polar features that make it a
      perfect material for those applications graphene is not suitable for, for
      example, purely ionic conductors, insulating membranes, transparent coatings,
      composite ceramics, high oxidation resistance materials. We report here a
      selective rim-functionalization of h-BN with SiO2 by using the Stober process. A
      closed, protruding ring of SiO2 is formed covering all edges perpendicular to the
      [001] zones of the h-BN stacks and thus shield the most reactive centers of BN
      layers. SEM and HAADF-STEM images, X-ray spectroscopy, and atomic force
      microscopy confirm the rim-functionalization by SiO2 . XRD demonstrates the
      absence of any intercalation phenomenon of BN and reveals the glassy nature of
      the SiO2 rims. Selected variations of synthesis and theoretical modeling both
      confirm that rim activation by water prior to the Stober condensation is crucial.
      First-principles calculations also confirm that dangling bonds of clean BN edges
      merge to give interlayer bonds that make further functionalization much more
      difficult. The reported reaction pathway should allow for other new
      functionalizations of pure BN and of the rimmed SiO2 /h-BN composites. 

PMID- 25873401
TI  - Centromere-associated meiotic drive and female fitness variation in Mimulus.
AB  - Female meiotic drive, in which chromosomal variants preferentially segregate to
      the egg pole during asymmetric female meiosis, is a theoretically pervasive but
      still mysterious form of selfish evolution. Like other selfish genetic elements,
      driving chromosomes may be maintained as balanced polymorphisms by pleiotropic or
      linked fitness costs. A centromere-associated driver (D) with a ~58:42 female
      specific transmission advantage occurs at intermediate frequency (32-40%) in the
      Iron Mountain population of the yellow monkeyflower, Mimulus guttatus. Previously
      determined male fertility costs are sufficient to prevent the fixation of D, but
      predict a higher equilibrium frequency. To better understand the dynamics and
      effects of D, we developed a new population genetic model and measured genotype
      specific lifetime female fitness in the wild. In three of four years, and across
      all years, D imposed significant recessive seedset costs, most likely due to
      hitchhiking by deleterious mutations. With both male and female costs as
      measured, and 58:42 drive, our model predicts an equilibrium frequency of D (38%)
      very close to the observed value. Thus, D represents a rare selfish genetic
      element whose local population genetic dynamics have been fully parameterized,
      and the observation of equilibrium sets the stage for investigations of
      coevolution with suppressors.

PMID- 25873402
TI  - MicroRNA-494 sensitizes colon cancer cells to fluorouracil through regulation of
      DPYD.
AB  - Chemoresistance of colon cancer cells to the chemotherapeutics is still a main
      obstacle in treatment of this malignancy. The microRNA (miRNA) mediated
      chemosensitivity regulation in colon cancer cells is still largely unknown. Here
      we constructed a fluorouracil (5-Fu) resistant SW480 cell line (SW480/5-Fu) and
      discovered that miRNA miR-494 was down-regulated in the drug resistant cells
      compared with the parental cells. miR-494 level was found to be correlated with 5
      Fu sensitivity in colon cancer cells, and artificial alteration of miR-494
      affects the sensitivity of colon cancer cell lines to 5-Fu. miR-494 also promoted
      apoptosis of colon cancer cells at present of 5-Fu. Importantly, as a regulatory
      enzyme in the 5-Fu catabolic pathway, DPYD was confirmed to be a direct target of
      miR-494 through the interaction of miR-494 and its binding site within DPYD 3'
      untranslated region (3'UTR). miR-494 also negatively regulated endogenous DPYD
      expression in SW480 cells. Overexpression or knockdown of DPYD could attenuate
      miR-494 mediated 5-Fu sensitivity regulation, suggesting the dependence of DPYD
      regulation in miR-494 activity. miR-494 inhibited SW480/5-Fu derived xenograft
      tumors growth in vivo at present of 5-Fu. Thus, we concluded that in colon cancer
      cells, tumor suppressor miR-494 enhanced 5-Fu sensitivity via regulation of DPYD
      expression.

PMID- 25873403
TI  - Synthesis of a novel organic-inorganic hybrid of polyaniline/titanium phosphate
      for Re(VII) removal.
AB  - The organic-inorganic hybrid material of polyaniline/titanium(IV)
      (PANI/Ti(HPO4)2) was synthesized by an oxidative polymerization reaction. The
      PANI/Ti(HPO4)2 was applied to remove Re(VII). The size of Ti(HPO4)2 nanoplates
      has no obvious effect on the sorption capacity. The effects of various
      environmental factors (such as pH, extra anions (NO3(-) and MO4(2-)) and
      temperature) on Re(VII) sorption to PANI/Ti(HPO4)2 were investigated by batch
      experiments. The sorption kinetics followed a pseudo-second-order model. The
      nitrogen-containing functional groups of PANI promoted Re(VII) sorption. The
      PANI/Ti(HPO4)2 exhibited excellent maximum sorption capacity to Re(VII) (47.62 mg
      g(-1)), which was superior to that of PANI (10.75 mg g(-1)) and much higher than
      that of many other sorbents. The sorption isotherms of Re(VII) can be well fitted
      with the Langmuir model. Re(VII) sorption decreased with increasing solution pH
      at pH > 4.0, which implied that Re(VII) sorption on PANI/Ti(HPO4)2 might be
      attributed to the outer-sphere complexation between amine and imine groups on the
      surface of PANI/Ti(HPO4)2 and Re(VII). This study implies that the hybrid
      material of PANI/Ti(HPO4)2 can be regarded as a potential sorbent to remove
      Re(VII) and its analogues from large volumes of aqueous solutions.

PMID- 25873404
TI  - Asymmetric palladium-catalyzed umpolung cyclization of allylic acetate-aldehyde
      using formate as a reductant.
AB  - Palladium/chiral diphosphine-catalyzed umpolung cyclization of allylic acetate
      aldehyde using formate as a terminal reductant affords cis-disubstituted
      pyrrolidine, tetrahydrofuran, and spiro carbocycle in high enantioselectivity.
      The formate does not cause allylpalladium reduction under the catalysis. The
      highly stereoselective cyclization would proceed through a cationic eta(1)
      allylpalladium ligated by diphosphine. 

PMID- 25873406
TI  - Updating SIDS risk reduction advice has the potential to further reduce infant
      deaths in Sweden.

PMID- 25873407
TI  - The potential for harm from alarm fatigue in single-room NICUs.

PMID- 25873408
TI  - Commentary on regional differences in postneonatal childhood mortality in
      Finland, 1985-2004.

PMID- 25873409
TI  - Successes and challenges in infant mortality.

PMID- 25873410
TI  - Robert B. Cotton recalled as devoted teacher, mentor, and scientist.

PMID- 25873411
TI  - Anatomoclinical study of 30 cases of sclerosing sweat duct carcinomas
      (microcystic adnexal carcinoma, syringomatous carcinoma and squamoid eccrine
      ductal carcinoma).
AB  - BACKGROUND: Microcystic adnexal carcinoma (MAC), syringomatous carcinoma (SC) and
      "Squamoid eccrine ductal carcinoma" (SEDC) are rare sclerosing adnexal tumours.
      OBJECTIVE: To understand the histogenesis of these tumours and possible clinical
      implications. METHODS: We conducted a retrospective study of 30 cases, 18 MAC, 5
      SC and 7 SEDC reviewed and classified by a panel of dermatopathology experts,
      with immunohistochemical analysis of keratins, including K77, a new keratin
      specific of eccrine ducts, and PHLDA1 expressed in adnexal structures. RESULTS:
      There was a strong female predominance, with only five cases occurring in men.
      Patients with MAC and SC were younger (mean age 56 and 47 years) than those with
      SEDC (mean age 81 years). The most common localization was the cheek in SC and
      SEDC and the periocular area in MAC. Two cases of SEDC were found in organ
      transplant patients. No recurrence or metastases were observed after complete
      surgery of MAC, or SC (mean follow-up 7.2 years and 4.7 years), whereas one case
      of SEDC recurred and another could not be fully excised. MAC and SC had similar
      histological features, except for cysts. In MAC, calcifications, granulomas,
      connection to follicles, keratin expression pattern, PHLDA1 positivity and K77
      negativity indicated a follicular histogenesis, whereas in SC, K77 positivity and
      keratin expression pattern were consistent with a differentiation towards eccrine
      apparatus. SEDC was composed of strands centred by ducts and nests with squamous
      differentiation and displayed K77 ductal positivity in all cases, a finding
      consistent with an eccrine origin. CONCLUSION: Our study demonstrated that MAC
      and SC have similar clinical characteristics, although histogenesis differs and
      show arguments for the individualization of SEDC.

PMID- 25873412
TI  - Detection of serum anti-NV-F antibodies in the convalescent phase of severe
      hepatitis in patients positive for tissue NV-F antigen and novel virus-like
      particles.
AB  - Previously, a non-human DNA fragment named NV-F was isolated from a patient with
      non-A-E fulminant hepatitis. This sequence encoded an incomplete open reading
      frame (the NV-F antigen). In this study, we developed a western blot assay to
      detect serum anti-NV-F antibodies. Serum samples from 347 patients with severe
      hepatitis (ALT > fivefold ULN) were analyzed to understand the prevalence and
      distribution of the NV-F associated virus (HnFV) infection. Of these patients,
      acute HnFV infection was diagnosed (by positive serum NV-F DNA) in 34 patients
      (9.8%). However, none of these 34 serum samples were positive for serum anti-NV-F
      antibodies. In the remaining patients negative for serum NV-F DNA, 62 (17.9%)
      were positive for serum anti-NV-F antibodies. Liver biopsy samples from 35 severe
      hepatitis patients were submitted for immunohistochemistry and electron
      microscopy examination. Of them, seven were positive for hepatic NV-F antigen
      expression. Electron microscopy identified a novel virus-like particle in all of
      the seven NV-F antigen-positive liver tissues but not in the remaining 28 NV-F
      antigen-negative liver tissues. Longitudinal serum sample analysis revealed
      transient positivity of serum NV-F DNA in three of the seven patients during the
      clinical courses. Seroconversion of anti-NV-F antibody from negative to positive
      was found in four of the seven patients and all positive anti-NV-F antibodies
      were detected in the convalescent phases. In conclusion, in patients with severe
      hepatitis, a novel hepatotropic virus, temporarily named HnFV, was found in liver
      tissues expressing the NV-F antigen. Serum anti-NV-F antibodies were detected in
      the convalescent serum samples.

PMID- 25873413
TI  - Drug users should be able to get heroin from the health system.

PMID- 25873414
TI  - Non-invasive differentiation of kidney stone types using X-ray dark-field
      radiography.
AB  - Treatment of renal calculi is highly dependent on the chemical composition of the
      stone in question, which is difficult to determine using standard imaging
      techniques. The objective of this study is to evaluate the potential of scatter
      sensitive X-ray dark-field radiography to differentiate between the most common
      types of kidney stones in clinical practice. Here, we examine the absorption-to
      scattering ratio of 118 extracted kidney stones with a laboratory Talbot-Lau
      Interferometer. Depending on their chemical composition, microscopic growth
      structure and morphology the various types of kidney stones show strongly
      varying, partially opposite contrasts in absorption and dark-field imaging. By
      assessing the microscopic calculi morphology with high resolution micro-computed
      tomography measurements, we illustrate the dependence of dark-field signal
      strength on the respective stone type. Finally, we utilize X-ray dark-field
      radiography as a non-invasive, highly sensitive (100%) and specific (97%) tool
      for the differentiation of calcium oxalate, uric acid and mixed types of stones,
      while additionally improving the detectability of radio-lucent calculi. We prove
      clinical feasibility of the here proposed method by accurately classifying renal
      stones, embedded within a fresh pig kidney, using dose-compatible measurements
      and a quick and simple visual inspection. 

PMID- 25873415
TI  - Synthesis of centimeter-scale monolayer tungsten disulfide film on gold foils.
AB  - We report the synthesis of centimeter-scale monolayer WS2 on gold foil by
      chemical vapor deposition. The limited tungsten and sulfur solubility in gold
      foil allows monolayer WS2 film growth on gold surface. To ensure the coverage
      uniformity of monolayer WS2 film, the tungsten source-coated substrate was placed
      in parallel with Au foil under hydrogen sulfide atmosphere. The high growth
      temperature near 935  degrees C helps to increase a domain size up to 420 MUm.
      Gold foil is reused for the repeatable growth after bubbling transfer. The WS2
      based field effect transistor reveals an electron mobility of 20 cm(2) V(-1) s(
      1) with high on-off ratio of ~10(8) at room temperature, which is the highest
      reported value from previous reports of CVD-grown WS2 samples. The on-off ratio
      of integrated multiple FETs on the large area WS2 film on SiO2 (300 nm)/Si
      substrate shows within the same order, implying reasonable uniformity of WS2 FET
      device characteristics over a large area of 3 * 1.5 cm(2). 

PMID- 25873416
TI  - Anatomy of the hip capsule and pericapsular structures: A cadaveric study.
AB  - The anatomical literature contains relatively little qualitative or quantitative
      information regarding the anatomy of the hip joint capsule and its relationship
      to the surrounding pericapsular structures. We aimed to provide a detailed
      description of the anatomy of these relationships in a cadaveric study.
      Dissections of 11 nonpaired, fresh-frozen cadaveric hips were performed,
      documenting capsular dimensions and attachments to pericapsular structures
      including the rectus femoris, gluteus minimus, iliocapsularis, and piriformis and
      short external rotator muscles. Tendon footprints of these pericapsular muscles
      were measured, as well as their distance from reproducible bony landmarks. The
      thickest portion of the hip capsule is posterosuperiorly and superiorly near its
      acetabular origin, while the thinnest portion is posteriorly and
      posteroinferiorly near its femoral insertion. The piriformis has no capsular
      contribution; however, the reflected head of the rectus femoris, gluteus minimus,
      iliocapsularis, and external rotator tendons all demonstrate consistent capsular
      adhesions. There are complex associations among these structures, yet the
      surrounding layers of the capsule are confluent in predictable relationships.
      Knowledge of the intricate relationship between the hip capsule and pericapsular
      structures presented here will be useful for surgeons as they perform the precise
      and specific capsular releases required by various operative procedures. This
      study also provides information that can lead to further biomechanical,
      radiographic, and clinical studies on these structures.

PMID- 25873417
TI  - Positive Effect of Water in Asymmetric Direct Aldol Reactions with Primary Amine
      Organocatalyst: Experimental and Computational Studies.
AB  - The origin of higher reactivity in water-accelerated asymmetric aldol reactions
      with our designed primary amine organocatalyst was elucidated by both
      computational and experimental methods. As suggested by the calculated transition
      state structures for water-promoted imine-enamine isomerization, anti-selective
      aldol reaction and hemiaminal formation, the rate of this aldol reaction was
      found experimentally to be even more accelerated by the addition of cis-2-butene
      1,4-diol as additive. 

PMID- 25873418
TI  - Intrinsically impaired platelet production in some patients with persistent or
      chronic immune thrombocytopenia.
AB  - Persistent or chronic immune thrombocytopenias (P/C-ITP) are acquired blood
      disorders lasting more than 3 months or 1 year, respectively. The pathogenesis of
      these disorders is thought to be immunological. We hypothesized that some
      patients with P/C-ITP might have an intrinsic megakaryopoiesis defect. We
      identified a group of P/C-ITP patients with acquired isolated mild
      thrombocytopenia (30-100 * 10(9) /l), undetectable anti-platelet antibodies,
      negative autoimmune investigations and no need for treatment. We examined in
      vitro megakaryocyte differentiation and compared these patients' results with
      those of acute-ITP patients and healthy controls. No difference in proliferation,
      ploidy or expression of surface markers was found. In contrast, P/C-ITP patients
      had significantly fewer proplatelet-forming megakaryocytes. This novel
      observation demonstrated that some patients diagnosed with P/C-ITP have an
      intrinsic megakaryopoiesis defect independent of the bone-marrow environment.
      Further investigations are needed to dissect mechanisms underlying this impaired
      proplatelet formation in these patients. 

PMID- 25873419
TI  - A novel method to determine the elastic modulus of extremely soft materials.
AB  - Determination of the elastic moduli of extremely soft materials that may deform
      under their own weight is a rather difficult experimental task. A new method has
      been elaborated by means of which the elastic modulus of such materials can be
      determined. This method is generally applicable to all soft materials with purely
      neo-Hookean elastic deformation behaviour with elastic moduli lower than 1 kPa.
      Our novel method utilises the self-deformation of pendent gel cylinders under
      gravity. When suspended, the material at the very top bears the weight of the
      entire gel cylinder, but that at the bottom carries no load at all. Due to the
      non-uniform stress distribution along the gel sample both the stress and the
      resulting strain show position dependence. The cross-sectional area of the
      material is lowest at the top of the sample and gradually increases towards its
      bottom. The equilibrium geometry of the pendant gel is used to evaluate the
      elastic modulus. Experimental data obtained by the proposed new method were
      compared to the results obtained from underwater measurements. The parameters
      affecting the measurement uncertainty were studied by a Pareto analysis of a
      series of adaptive Monte Carlo simulations. It has been shown that our method
      provides an easily achievable method to provide an accurate determination of the
      elastic modulus of extremely soft matter typically applicable for moduli below 1
      kPa. 

PMID- 25873420
TI  - Conservation of resources theory and the 'strength' model of self-control:
      conceptual overlap and commonalities.

PMID- 25873421
TI  - The commerce and crossover of resources: resource conservation in the service of
      resilience.
AB  - Conservation of resources (COR) theory was originally introduced as a framework
      for understanding and predicting the consequences of major and traumatic stress,
      but following the work of Hobfoll and Shirom (1993), COR theory has been adopted
      to understanding and predicting work-related stress and both the stress and
      resilience that occur within work settings and work culture. COR theory
      underscores the critical role of resource possession, lack, loss and gain and
      depicts personal, social and material resources co-travelling in resource
      caravans, rather than piecemeal. We briefly review the principles of COR theory
      and integrate it in the crossover model, which provides a key mechanism for multi
      person exchange of emotions, experiences and resources. Understanding the impact
      of resource reservoirs, resource passageways and crossover provides a framework
      for research and intervention promoting resilience to employees as well as to
      organizations. It emphasizes that the creation and maintenance of resource
      caravan passageways promote resource gain climates through resource crossover
      processes.

PMID- 25873423
TI  - Chronological protein synthesis in regenerating rat liver.
AB  - Liver regeneration has been studied for decades; however, its regulation remains
      unclear. In this study, we report a dynamic tracing of protein synthesis in rat
      regenerating liver with a new proteomic technique, (35) S in vivo labeling
      analysis for dynamic proteomics (SiLAD). Conventional proteomic techniques
      typically measure protein alteration in accumulated amounts. The SiLAD technique
      specifically detects protein synthesis velocity instead of accumulated amounts of
      protein through (35) S pulse labeling of newly synthesized proteins, providing a
      direct way for analyzing protein synthesis variations. Consequently, protein
      synthesis within short as 30 min was visualized and protein regulations in the
      first 8 h of regenerating liver were dynamically traced. Further, the 3.5-5 h
      post partial hepatectomy (PHx) was shown to be an important regulatory turning
      point by acute regulation of many proteins in the initiation of liver
      regeneration. 

PMID- 25873424
TI  - Improved models for plasma radiometabolite correction and their impact on kinetic
      quantification in PET studies.
AB  - The quantification of dynamic positron emission tomography studies performed with
      arterial sampling usually requires correcting the input function for the presence
      of radiometabolites by using a model of the plasma parent fraction (PPf). Here,
      we show how to include the duration of radioligand injection in the PPf model
      formulations to achieve a more physiologic description of the plasma
      measurements. This formulation (here called convoluted model) was tested on
      simulated data and on three datasets with different parent kinetics: [(11)C]NOP
      1A, [(11)C]MePPEP, and [(11)C](R)-rolipram. Results showed that convoluted PPf
      models better described the fraction of unchanged parent in the plasma compared
      with standard models for all three datasets (weighted residuals sum of squares up
      to 25% lower). When considering the effect on tissue quantification, the overall
      impact on the total volume of distribution (VT) was low. However, the impact was
      significant and radioligand-dependent on the binding potential (BP) and the
      microparameters (K1, k2, k3, and k4). Simulated data confirmed that
      quantification is sensitive to different degrees to PPf model misspecification.
      Including the injection duration allows obtaining a more accurate correction of
      the input function for the presence of radiometabolites and this yields a more
      reliable quantification of the tissue parameters. 

PMID- 25873425
TI  - Quantification of blood flow-dependent component in estimates of beta-amyloid
      load obtained using quasi-steady-state standardized uptake value ratio.
AB  - Longitudinal positron emission tomography (PET) imaging of beta-amyloid is used
      in basic research and in drug efficacy trials in Alzheimer's disease (AD).
      However, the extent of amyloid accumulation after clinical onset is not fully
      known. Importantly, regional PET data are typically quantified using the
      standardized uptake value ratio (SUVR), which according to simulations is
      sensitive to changes in regional cerebral blood flow (rCBF). We aimed to better
      understand the potentials of longitudinal amyloid imaging by disentangling the
      influence of blood flow on SUVR using experimental data. [18F]AV-45 PET data from
      101 subjects, ranging from cognitively normal to AD patients, in the Alzheimer's
      Disease Neuroimaging Initiative were extracted. The relationship between global
      cortical distribution volume ratio, indicator of rCBF (R1), and SUVR was examined
      using multilinear regression. There was a significant effect of rCBF on SUVR. The
      effect increased by disease severity. Results suggest that changes in rCBF can
      produce apparent changes in SUVR in AD. Therefore, future longitudinal studies
      should measure amyloid changes in a way not sensitive to this effect, ideally
      using quantitative PET imaging. Furthermore, the results suggest no true
      accumulation beyond clinical onset and highlight the risks of longitudinal
      amyloid imaging in drug trials in AD. 

PMID- 25873426
TI  - Aberrant white matter networks mediate cognitive impairment in patients with
      silent lacunar infarcts in basal ganglia territory.
AB  - Silent lacunar infarcts, which are present in over 20% of healthy elderly
      individuals, are associated with subtle deficits in cognitive functions. However,
      it remains largely unclear how these silent brain infarcts lead to cognitive
      deficits and even dementia. Here, we used diffusion tensor imaging tractography
      and graph theory to examine the topological organization of white matter networks
      in 27 patients with silent lacunar infarcts in the basal ganglia territory and 30
      healthy controls. A whole-brain white matter network was constructed for each
      subject, where the graph nodes represented brain regions and the edges
      represented interregional white matter tracts. Compared with the controls, the
      patients exhibited a significant reduction in local efficiency and global
      efficiency. In addition, a total of eighteen brain regions showed significantly
      reduced nodal efficiency in patients. Intriguingly, nodal efficiency-behavior
      associations were significantly different between the two groups. The present
      findings provide new aspects into our understanding of silent infarcts that even
      small lesions in subcortical brain regions may affect large-scale cortical white
      matter network, as such may be the link between subcortical silent infarcts and
      the associated cognitive impairments. Our findings highlight the need for network
      level neuroimaging assessment and more medical care for individuals with silent
      subcortical infarcts. 

PMID- 25873427
TI  - Model-free quantification of dynamic PET data using nonparametric deconvolution.
AB  - Dynamic positron emission tomography (PET) data are usually quantified using
      compartment models (CMs) or derived graphical approaches. Often, however, CMs
      either do not properly describe the tracer kinetics, or are not identifiable,
      leading to nonphysiologic estimates of the tracer binding. The PET data are
      modeled as the convolution of the metabolite-corrected input function and the
      tracer impulse response function (IRF) in the tissue. Using nonparametric
      deconvolution methods, it is possible to obtain model-free estimates of the IRF,
      from which functionals related to tracer volume of distribution and binding may
      be computed, but this approach has rarely been applied in PET. Here, we apply
      nonparametric deconvolution using singular value decomposition to simulated and
      test-retest clinical PET data with four reversible tracers well characterized by
      CMs ([(11)C]CUMI-101, [(11)C]DASB, [(11)C]PE2I, and [(11)C]WAY-100635), and
      systematically compare reproducibility, reliability, and identifiability of
      various IRF-derived functionals with that of traditional CMs outcomes. Results
      show that nonparametric deconvolution, completely free of any model assumptions,
      allows for estimates of tracer volume of distribution and binding that are very
      close to the estimates obtained with CMs and, in some cases, show better test
      retest performance than CMs outcomes. 

PMID- 25873428
TI  - Carbon dioxide induced changes in cerebral blood flow and flow velocity: role of
      cerebrovascular resistance and effective cerebral perfusion pressure.
AB  - In addition to cerebrovascular resistance (CVR) zero flow pressure (ZFP),
      effective cerebral perfusion pressure (CPPe) and the resistance area product
      (RAP) are supplemental determinants of cerebral blood flow (CBF). Until now, the
      interrelationship of PaCO2-induced changes in CBF, CVR, CPPe, ZFP, and RAP is not
      fully understood. In a controlled crossover trial, we investigated 10
      anesthetized patients aiming at PaCO2 levels of 30, 37, 43, and 50 mm Hg.
      Cerebral blood flow was measured with a modified Kety-Schmidt-technique. Zero
      flow pressure and RAP was estimated by linear regression analysis of pressure
      flow velocity relationships of the middle cerebral artery. Effective cerebral
      perfusion pressure was calculated as the difference between mean arterial
      pressure and ZFP, CVR as the ratio CPPe/CBF. Statistical analysis was performed
      by one-way RM-ANOVA. When comparing hypocapnia with hypercapnia, CBF showed a
      significant exponential reduction by 55% and mean VMCA by 41%. Effective cerebral
      perfusion pressure linearly decreased by 17% while ZFP increased from 14 to 29 mm
      Hg. Cerebrovascular resistance increased by 96% and RAP by 39%; despite these
      concordant changes in mean CVR and Doppler-derived RAP correlation between these
      variables was weak (r=0.43). In conclusion, under general anesthesia hypocapnia
      induced reduction in CBF is caused by both an increase in CVR and a decrease in
      CPPe, as a consequence of an increase in ZFP. 

PMID- 25873429
TI  - Protective effects of low-intensity pulsed ultrasound on aluminum-induced
      cerebral damage in Alzheimer's disease rat model.
AB  - The protein expressions of neurotrophic factors can be enhanced by low-intensity
      pulsed ultrasound (LIPUS) stimulation in the brain. The purpose of this study was
      to demonstrate the protective effect of LIPUS stimulation against aluminum
      induced cerebral damage in Alzheimer's disease rat model. LIPUS was administered
      7 days before each aluminum chloride (AlCl3) administration, and concomitantly
      given with AlCl3 daily for a period of 6 weeks. Neurotrophic factors in
      hippocampus were measured by western blot analysis. Behavioral changes in the
      Morris water maze and elevated plus maze were examined in rats after
      administration of AlCl3. Various biochemical analyses were performed to evaluate
      the extent of brain damages. LIPUS is capable of prompting levels of brain
      derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor
      (GDNF), and vascular endothelial growth factor (VEGF) in rat brain. AlCl3
      administration resulted in a significant increase in the aluminum concentration,
      acetylcholinesterase activity and beta-amyloid (Abeta) deposition in AlCl3
      treated rats. LIPUS stimulation significantly attenuated aluminum concentration,
      acetylcholinesterase activity, Abeta deposition and karyopyknosis in AlCl3
      treated rats. Furthermore, LIPUS significantly improved memory retention in AlCl3
      induced memory impairment. These experimental results indicate that LIPUS has
      neuroprotective effects against AlCl3-induced cerebral damages and cognitive
      dysfunction. 

PMID- 25873430
TI  - Cocaine-related stimuli impair inhibitory control in cocaine users following
      short stimulus onset asynchronies.
AB  - BACKGROUND AND AIMS: Cocaine users display a significant increase in inhibitory
      failures following cocaine-related images compared with neutral images in a
      modified cued Go/No-Go task, the Attentional Bias-Behavioral Activation (ABBA)
      task. The aim of this study was to demonstrate that stimulus onset asynchrony
      (SOA) impacts inhibitory failures on the ABBA task. DESIGN: A between-subjects
      experiment. SETTING: An out-patient research unit in the United States.
      PARTICIPANTS: Ninety-one cocaine users recruited from the community.
      MEASUREMENTS: Participants were assigned to groups in which they saw either
      cocaine (n=46) or neutral (n=45) images as the go condition. Cues were presented
      for one of five SOAs (i.e. 100, 200, 300, 400 or 500 ms) before a go or no-go
      target was displayed. FINDINGS: Participants in the cocaine go condition had a
      significantly higher proportion of inhibitory failures to no-go targets
      (F4,356=2.50, P=0.04) with significantly more inhibitory failures following all
      SOAs (P<0.05) than those in the neutral go condition. Within the cocaine go
      condition, significantly more inhibitory failures were observed following the 100
      and 200 ms SOAs than after the 300, 400 or 500 ms SOAs (P<0.05). CONCLUSIONS:
      Cocaine-related stimuli appear to decrease inhibitory control in cocaine users at
      short (100 and 200 ms) stimulus onset asynchronies (SOAs: the amount of time
      between the start of one stimulus and the start of another stimulus), but not at
      longer (300, 400 and 500 ms) SOAs.

PMID- 25873431
TI  - Acidified bile acids increase hTERT expression via c-myc activation in human
      gastric cancer cells.
AB  - Human telomerase reverse transcriptase (hTERT) is upregulated in most cancer cell
      types as well in immortalized cells. The underlying mechanism for such
      upregulation, however, remains largely unknown. We report here that bile acids
      under acidified media increase hTERT expression via c-myc activation in primary
      human gastric cancer cell lines. Human gastric cancer MKN28, MGC803 and SGC7901
      cells were treated with 100 uM deoxycholic acid (DCA) or chenodeoxycholic acid
      (CDCA) with or without acidified media in the presence or absence of the c-myc
      inhibitor 10058-F4 for 24 h. hTERT and c-myc protein levels were determined by
      western blot analysis. hTERT and c-myc mRNA levels were determined by RT-PCR. The
      promoter activities of hTERT and c-myc transcription were determined using
      promoter reporter luciferase assays for both. Telomerase enzyme activity was
      analyzed by stretch PCR. hTERT mRNA and protein levels were significantly
      increased by bile acids in acidified media and were accompanied with enhanced
      telomerase activity. No changes were found at a pH of 7.0 or with acidified media
      alone. Similarly, the mRNA and protein levels of c-myc were also increased by
      bile acids in acidified media but not at a pH of 7.0 or with acidified media
      alone. Importantly, pharmacologic inhibition of c-myc using 10058-F4 prevented
      hTERT induction by DCA or CDCA in gastric cancer cells under acidic conditions.
      Bile acids (DCA and CDCA) under acidic conditions increased hTERT expression in
      human gastric cancer cells by activation of c-myc transcription. This suggests
      that acidified bile acids may promote tumorigenesis and affect cell ageing via
      telomerase activation.

PMID- 25873432
TI  - Testing the main hypotheses of the interpersonal-psychological theory of suicidal
      behavior in a large diverse sample of United States military personnel.
AB  - BACKGROUND: Preliminary data indicate the suicide rate in the United States
      military decreased in 2013, but the National Guard saw a continued increase.
      METHOD: We examined the utility of the interpersonal-psychological theory of
      suicidal behavior (IPTS) in a sample of US military personnel drawn largely from
      the National Guard (n=934; 77.7% male; 59.5% white). RESULTS: Results indicated
      the interaction of thwarted belongingness and perceived burdensomeness predicted
      suicidal ideation and resolved plans and preparations for suicide. In each case,
      risk was greatest at higher levels of both predictors. Furthermore, results
      indicated the interaction of thwarted belongingness, perceived burdensomeness,
      and acquired capability for suicide predicted prior suicide attempts. In this
      interaction term, the relationship between suicidal desire (thwarted
      belongingness and perceived burdensomeness) and suicide attempts was significant
      and positive only at high levels of acquired capability. All analyses were cross
      sectional. CONCLUSIONS: Results indicate the IPTS may be useful for
      conceptualizing suicide risk in the National Guard.

PMID- 25873433
TI  - Assessing the effectiveness of decision aids for decision making in prostate
      cancer testing: a systematic review.
AB  - BACKGROUND: Prostate cancer is a leading disease affecting men worldwide.
      Conflicting evidence within the literature provides little guidance to men
      contemplating whether or not to be screened for prostate cancer. This systematic
      review aimed to determine whether decision aids about early detection of prostate
      cancer improve patient knowledge and decision making about whether to undergo
      prostate-specific antigen testing. METHODS: Medline, EMBASE, CINAHL, PsychINFO,
      Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of
      Effects and Health Technology Assessment databases up until March 2014 were
      searched. All included randomised controlled trials were assessed for
      methodological quality. Clinical selection and assessment heterogeneity among
      studies prevented the pooling of data for meta-analyses. Descriptive analyses of
      all included studies and comparison were performed. RESULTS: A total of 13
      randomised controlled trials met the inclusion criteria. Significant
      heterogeneity was present for the design and implementation of decision aids
      including comparative interventions and outcomes. Eight studies were of a low
      methodological quality, with the remaining five of medium quality. Improvements
      in patient knowledge following use of a decision aid were demonstrated by 11 of
      the 13 included studies. Seven of 10 studies demonstrated a reduction in
      decisional conflict/distress. Three of four studies demonstrated no difference
      between a decision aid and information only in reducing decisional uncertainty.
      Three of five studies demonstrated an increase in decisional satisfaction with
      use of a decision aid. CONCLUSIONS: Decision aids increase patient knowledge and
      confidence in decision making about prostate cancer testing. Further research
      into effective methods of implementation is needed. Copyright (c) 2015 John Wiley
      & Sons, Ltd.

PMID- 25873434
TI  - Designed enclosure enables guest binding within the 4200 a(3) cavity of a self
      assembled cube.
AB  - Metal-organic self-assembly has proven to be of great use in constructing
      structures of increasing size and intricacy, but the largest assemblies lack the
      functions associated with the ability to bind guests. Here we demonstrate the
      self-assembly of two simple organic molecules with Cd(II) and Pt(II) into a giant
      heterometallic supramolecular cube which is capable of binding a variety of mono-
      and dianionic guests within an enclosed cavity greater than 4200 A(3) . Its
      structure was established by X-ray crystallography and cryogenic transmission
      electron microscopy. This cube is the largest discrete abiological assembly that
      has been observed to bind guests in solution; cavity enclosure and coulombic
      effects appear to be crucial drivers of host-guest chemistry at this scale. The
      degree of cavity occupancy, however, appears less important: the largest guest
      studied, bound the most weakly, occupying only 11 % of the host cavity.

PMID- 25873435
TI  - Estimating phylogenetic trees from genome-scale data.
AB  - The heterogeneity of signals in the genomes of diverse organisms poses challenges
      for traditional phylogenetic analysis. Phylogenetic methods known as "species
      tree" methods have been proposed to directly address one important source of gene
      tree heterogeneity, namely the incomplete lineage sorting that occurs when
      evolving lineages radiate rapidly, resulting in a diversity of gene trees from a
      single underlying species tree. Here we review theory and empirical examples that
      help clarify conflicts between species tree and concatenation methods, and
      misconceptions in the literature about the performance of species tree methods.
      Considering concatenation as a special case of the multispecies coalescent model
      helps explain differences in the behavior of the two methods on phylogenomic data
      sets. Recent work suggests that species tree methods are more robust than
      concatenation approaches to some of the classic challenges of phylogenetic
      analysis, including rapidly evolving sites in DNA sequences and long-branch
      attraction. We show that approaches, such as binning, designed to augment the
      signal in species tree analyses can distort the distribution of gene trees and
      are inconsistent. Computationally efficient species tree methods incorporating
      biological realism are a key to phylogenetic analysis of whole-genome data. 

PMID- 25873436
TI  - Prognostic effect of comorbidity indices in elderly patients with multiple
      myeloma.
AB  - BACKGROUND: Consideration of comorbidity, disability, and frailty represents a
      significant part of the treatment of elderly multiple myeloma (MM) patients. The
      aim of study was to analyze the effect of the Charlson Comorbidity Index (CCI)
      and scale of Instrumental Activities of Daily Living (IADL) on the course of
      disease. PATIENTS AND METHODS: The study included 110 newly diagnosed MM patients
      older than 65 years of age. According to the CCI most patients had at least 1
      comorbidity (CCI score of 1) and most of them (51 of 110 patients; 46.4%) had an
      age-adjusted CCI (aaCCI) score of 5 to 6. Most of our patients were capable of
      performing routine daily activities (IADL >= 6). Patients were treated with
      thalidomide- and bortezomib- based combinations, or with conventional
      chemotherapy. RESULTS: International Staging System (ISS) score 3 correlated with
      high scores of CCI or aaCCI (R = 0.314, P < .003; R = .317, P < .002,
      respectively), and lower IADL (R = 0.259, P < .007). The probability of adverse
      events was 70% greater for CCI score >= 2 (odds ratio [OR], 1.72); 28% for aaCCI
      >= 5 (OR, 1.28) and 22% higher for IADL < 3 (OR, 2.25). The patients with a CCI
      score of 0 to 1 had significantly longer overall survival (OS; log rank, 6.538; P
      < .011). The patients with aaCCI >= 5 had significantly shorter OS (log rank,
      4.209; P < .040), and the patients with IADL > 3 had significantly longer OS (log
      rank, 6.62; P < .001). In the proposed model, aaCCI >= 5 and IADL > 3 scores had
      a major effect on the OS (chi(2), 8.46; P = .037). CONCLUSION: CCI, aaCCI, and
      IADL scale are clinical parameters of prognostic significance. A proposed model
      for a personalized treatment approach is based on variables such as scores for
      aaCCI >= 5 and IADL > 3.

PMID- 25873438
TI  - Google search behavior for status epilepticus.
AB  - BACKGROUND: Millions of people surf the Internet every day as a source of health
      care information looking for materials about symptoms, diagnosis, treatments and
      their possible adverse effects, or diagnostic procedures. Google is the most
      popular search engine and is used by patients and physicians to search for online
      health-related information. This study aimed to evaluate changes in Google search
      behavior occurring in English-speaking countries over time for the term "status
      epilepticus" (SE). METHODS: Using Google Trends, data on global search queries
      for the term SE between the 1st of January 2004 and 31st of December 2014 were
      analyzed. Search volume numbers over time (downloaded as CSV datasets) were
      analyzed by applying the "health" category filter. RESULTS: The research trends
      for the term SE remained fairly constant over time. The greatest search volume
      for the term SE was reported in the United States, followed by India, Australia,
      the United Kingdom, Canada, the Netherlands, Thailand, and Germany. Most terms
      associated with the search queries were related to SE definition, symptoms,
      subtypes, and treatment. The volume of searches for some queries (nonconvulsive,
      focal, and refractory SE; SE definition; SE guidelines; SE symptoms; SE
      management; SE treatment) was enormously increased over time (search popularity
      has exceeded a 5000% growth since 2004). CONCLUSIONS: Most people use search
      engines to look for the term SE to obtain information on its definition,
      subtypes, and management. The greatest search volume occurred not only in
      developed countries but also in developing countries where raising awareness
      about SE still remains a challenging task and where there is reduced public
      knowledge of epilepsy. Health information seeking (the extent to which people
      search for health information online) reflects the health-related information
      needs of Internet users for a specific disease. Google Trends shows that Internet
      users have a great demand for information concerning some aspects of SE
      (definition, subtypes, symptoms, treatment, and guidelines). Policy makers and
      neurological scientific societies have the responsibility to try to meet these
      information needs and to better target public information campaigns on SE to the
      general population. This article is part of a Special Issue entitled "Status
      Epilepticus".

PMID- 25873437
TI  - Functional connectivity homogeneity correlates with duration of temporal lobe
      epilepsy.
AB  - Temporal lobe epilepsy (TLE) is often associated with progressive changes to
      seizures, memory, and mood during its clinical course. However, the cerebral
      changes related to this progression are not well understood. Because the changes
      may be related to changes in brain networks, we used functional connectivity MRI
      (fcMRI) to determine whether brain network parameters relate to the duration of
      TLE. Graph theory-based analysis of the sites of reported regions of TLE
      abnormality was performed on resting-state fMRI data in 48 subjects: 24 controls,
      13 patients with left TLE, and 11 patients with right TLE. Various network
      parameters were analyzed including betweenness centrality (BC), clustering
      coefficient (CC), path length (PL), small-world index (SWI), global efficiency
      (GE), connectivity strength (CS), and connectivity diversity (CD). These were
      compared for patients with TLE as a group, compared to controls, and for patients
      with left and right TLE separately. The association of changes in network
      parameters with epilepsy duration was also evaluated. We found that CC, CS, and
      CD decreased in subjects with TLE compared to control subjects. Analyzed
      according to epilepsy duration, patients with TLE showed a progressive reduction
      in CD. In conclusion, we found that several network parameters decreased in
      patients with TLE compared to controls, which suggested reduced connectivity in
      TLE. Reduction in CD associated with epilepsy duration suggests a homogenization
      of connections over time in TLE, indicating a reduction of the normal repertoire
      of stronger and weaker connections to other brain regions. 

PMID- 25873439
TI  - A career in nursing research: A personal journey.

PMID- 25873440
TI  - Theoretical studies on the kinetics of hydrogen abstraction reactions of H and
      CH3 radicals from CH3OCH3 and some of their H/D isotopologues.
AB  - The hydrogen abstraction reactions by H and CH3 radicals from CH3OCH3 and some of
      their H/D isotopologues are studied by semiclassical transition state theory.
      Many high-level density functional, ab initio, and combinatory quantum chemical
      methods, including B3LYP, BB1K, MP2, MP4, CCSD(T), CBS-Q, and G4 methods, are
      employed to compute the energies and rovibrational properties of the stationary
      points for the title reactions. Xij vibrational anharmonicity coefficients, used
      in semiclassical transition state theory, are computed at the B3LYP, BB1K, and
      MP2 levels of theory. Thermal rate coefficients and kinetic isotope effects are
      computed over the temperature range from 200 to 2500 K and compared with
      available experimental data. The computed rate constants for the title reactions
      are represented as the equation k(T) = ATn exp[-E(T + T0)/(T2 + T02)].

PMID- 25873441
TI  - Function discovery and structural characterization of a methylphosphonate
      esterase.
AB  - Pmi1525, an enzyme of unknown function from Proteus mirabilis HI4320 and the
      amidohydrolase superfamily, was cloned, purified to homogeneity, and functionally
      characterized. The three-dimensional structure of Pmi1525 was determined with
      zinc and cacodylate bound in the active site (PDB id: 3RHG ). The structure was
      also determined with manganese and butyrate in the active site (PDB id: 4QSF ).
      Pmi1525 folds as a distorted (beta/alpha)8-barrel that is typical for members of
      the amidohydrolase superfamily and cog1735. The substrate profile for Pmi1525 was
      determined via a strategy that marshaled the utilization of bioinformatics,
      structural characterization, and focused library screening. The protein was found
      to efficiently catalyze the hydrolysis of organophosphonate and carboxylate
      esters. The best substrates identified for Pmi1525 are ethyl 4-nitrophenylmethyl
      phosphonate (kcat and kcat/Km values of 580 s(-1) and 1.2 * 10(5) M(-1) s(-1),
      respectively) and 4-nitrophenyl butyrate (kcat and kcat/Km values of 140 s(-1)
      and 1.4 * 10(5) M(-1) s(-1), respectively). Pmi1525 is stereoselective for the
      hydrolysis of chiral methylphosphonate esters. The enzyme hydrolyzes the (SP)
      enantiomer of isobutyl 4-nitrophenyl methylphosphonate 14 times faster than the
      corresponding (RP)-enantiomer. The catalytic properties of this enzyme make it an
      attractive template for the evolution of novel enzymes for the detection,
      destruction, and detoxification of organophosphonate nerve agents.

PMID- 25873442
TI  - Relations among suicidality, recent/frequent alcohol use, and gender in a black
      american adolescent sample: a longitudinal investigation.
AB  - OBJECTIVE: Examine longitudinally select factors that may contribute to suicide
      ideations and attempts in adolescents. METHOD: Using a multiple cohort research
      design, surveys were administered to a longitudinal sample of Black American
      adolescents aged 11-18 years. RESULTS: Two logistic growth models were tested
      with the probability of a suicide ideation (n = 977) and identified suicide
      attempt (n = 457) as the outcome variables and the recency and frequency of
      alcohol use and gender as the predictor variables. The recency and frequency of
      alcohol use was significantly related to suicide ideations and identified
      attempts in both females and males. These findings were differentiated based on
      the age effects for recency and frequency of alcohol use. More recent and
      frequent alcohol use among younger adolescents exacerbated probabilities of
      suicide ideations and identified suicide attempts compared to older adolescents.
      CONCLUSION: Results indicate that early systematic assessment of suicidal
      behavior and alcohol use in Black American adolescents can inform developmentally
      and culturally responsive prevention and intervention efforts.

PMID- 25873443
TI  - Helicobacter pylori-related ApoE 4 polymorphism may be associated with dysphagic
      symptoms in older adults.

PMID- 25873444
TI  - Stereotactic radiosurgery in the management of vestibular schwannoma and glomus
      jugulare: indications, techniques, and results.
AB  - Gamma Knife stereotactic radiosurgery (GKS) has become an important management
      strategy for an increasing number of patients with skull base tumors. For select
      patients with lateral skull base disorders, given the proximity to sensitive
      critical structures such as the brainstem, cranial nerves, and cochlea, this
      technology has emerged as a first-line treatment to achieve the paramount goals
      of long-term tumor control and maintenance of existing neurologic function. This
      article reviews the indications, technique, and results of GKS for the treatment
      of vestibular schwannoma and glomus jugulare tumors, and highlights our
      experience in treating these tumors at the Mayo Clinic. 

PMID- 25873445
TI  - Sampling of Glycan-Bound Conformers by the Anti-HIV Lectin Oscillatoria agardhii
      agglutinin in the Absence of Sugar.
AB  - Lectins from different sources have been shown to interfere with HIV infection by
      binding to the sugars of viral-envelope glycoproteins. Three-dimensional atomic
      structures of a number of HIV-inactivating lectins have been determined, both as
      free proteins and in glycan-bound forms. However, details on the mechanism of
      recognition and binding to sugars are elusive. Herein we focus on the anti-HIV
      lectin OAA from Oscillatoria agardhii: We show that in the absence of sugars in
      solution, both the sugar-free and sugar-bound protein conformations that were
      observed in the X-ray crystal structures exist as conformational substates. Our
      results suggest that glycan recognition occurs by conformational selection within
      the ground state; this model differs from the popular "excited-state" model. Our
      findings provide further insight into molecular recognition of the major receptor
      on the HIV virus by OAA. These details can potentially be used for the
      optimization and/or development of preventive anti-HIV therapeutics. 

PMID- 25873447
TI  - Abstracts of the RCOG World Congress 2015, 12-15 April, Brisbane, Queensland,
      Australia.

PMID- 25873446
TI  - Feasibility study: Assessing the influence of macronutrient intakes on preterm
      body composition, using air displacement plethysmography.
AB  - AIM: Preterm nutrition guidelines target nutrient accretion and growth at
      intrauterine rates, yet at term equivalent age, the phenotype of the preterm
      infant differs from that of term infants. Monitoring early changes in preterm
      body composition (BC) in response to macronutrient intakes may facilitate our
      understanding of how best to meet preterm nutrition and growth targets. METHOD:
      Macronutrient intakes based on milk analysis were calculated from birth for
      infants born <33 weeks gestation. BC was measured in the PEA POD when infants
      were thermodynamically stable, free of intravenous lines and independent of
      respiratory support. Subsequent BC measurements were taken at least fortnightly
      until term age. Regression analysis was used to assess macronutrient influences
      on changes in BC. RESULTS: Median (range) gestation and birthweight of preterm
      infants (n = 27) were 29 (25-32) weeks and 1395 (560-2148) g, respectively. The
      youngest corrected gestational and postnatal ages that infants qualified for a
      PEA POD measurement were 31.86 and 1.43 weeks, respectively. Fat and total energy
      intakes were positively associated with increasing fat mass. Protein (with
      carbohydrate) intake was positively associated with increasing fat-free mass.
      CONCLUSION: Preterm infants can be measured in the PEA POD as early as 31 weeks
      corrected gestational age and the method appears sufficiently sensitive to detect
      influences of macronutrient intake on changes in BC.

PMID- 25873448
TI  - Disparities in health-related quality of life among healthy adolescents in a
      developing country - the impact of gender, ethnicity, socio-economic status and
      weight status.
AB  - BACKGROUND: Physical functioning and psychological resilience in adulthood is
      shaped during adolescence. Self-reported health-related quality of life (HRQoL)
      assessments during this life phase are important first-hand accounts of their
      well-being. This study aimed, firstly, to identify differences in HRQoL according
      to gender, ethnicity, socio-economic status and weight status; and secondly, to
      examine associations between weight status and HRQoL among an urban sample of
      multi-ethnic adolescents in Kuala Lumpur, Malaysia. METHODS: A cross-sectional
      study involving 652 adolescents (aged 13 years) was conducted in Kuala Lumpur.
      Weight and height were measured. Body mass index z-scores were categorized
      according to the International Obesity Task Force criteria. HRQoL was assessed
      using the Malay version of the Pediatric Quality of Life Inventory 4.0 Generic
      Core Scales. Univariate analyses of differences in HRQoL according to gender,
      ethnicity (Malays, Chinese and Indians), maternal education level and weight
      status were performed. Complex samples general linear model was used to examine
      the associations between HRQoL and weight status, adjusted for confounders.
      RESULTS: Female adolescents reported significantly lower emotional functioning
      scores (mean, 95% confidence interval: 59.25, 57.33-61.17). When the three main
      ethnic groups were studied, Malay adolescents scored significantly lower
      emotional functioning scores (59.00, 57.13-60.87) compared with their Chinese
      peers. Adolescents with tertiary-educated mothers reported lower emotional
      functioning scores (57.45, 53.85-61.06) compared with those with primary-educated
      mothers. Obese adolescents reported poorer HRQoL scores with significantly
      impaired physical and social functioning after controlling for confounders.
      CONCLUSIONS: These findings detected disparities in HRQoL among the adolescents
      when gender, ethnicity, maternal education level and weight status were
      considered. Further studies should address these health inequalities by
      implementing gender-specific and culturally appropriate measures to attain
      optimal well-being and avoid potential burden of disease.

PMID- 25873449
TI  - Anti-Biofilm Efficacy of Dual-Action Nitric Oxide-Releasing Alkyl Chain Modified
      Poly(amidoamine) Dendrimers.
AB  - Herein, we describe the synthesis of nitric oxide (NO)-releasing alkyl chain
      modified poly(amidoamine) (PAMAM) dendrimers of various sizes (i.e.,
      generations). Generation 1 (G1) through generation 4 (G4) dendrimers were
      modified with either short (i.e., butyl) or medium (i.e., hexyl) alkyl chains via
      a ring-opening reaction. The resulting secondary amines were subsequently
      modified with N-diazeniumdiolate NO donors to establish NO payloads of ~1.0
      MUmol/mg. The bactericidal efficacy of these dendrimers was evaluated against
      Gram-negative and Gram-positive biofilms, including antibiotic-resistant strains.
      The anti-biofilm action of the dendrimer biocides was found to be dependent on
      dendrimer generation, bacterial Gram class, and alkyl chain length, with the most
      effective biofilm eradication occurring when antibacterial agents were capable of
      efficient biofilm infiltration. The addition of NO release markedly enhanced anti
      biofilm activity of dendrimers incapable of effective biofilm penetration. 

PMID- 25873450
TI  - Self-assembly and characterization of transferrin-gold nanoconstructs and their
      interaction with bio-interfaces.
AB  - Transferrin (Tf) conjugated to gold nanoparticles and clusters combine the
      protein's site-specific receptor targeting capabilities with the optical
      properties imparted by the nano-sized gold. We have described two different
      synthesis protocols, one yielding fluorescent Tf-stabilized gold nanoclusters
      (AuNCs) and one yielding Tf-stabilized gold nanoparticles that exhibit localized
      surface plasmon resonance. We demonstrate that the synthetic route employed has a
      large influence both on the gold nanostructure formed, and also on the structural
      integrity of the protein. A slight protein unfolding allows stronger interaction
      with lipids, and was found to significantly perturb lipid monolayers.
      Interactions between the protein-gold nanostructures and three different cell
      types were also assessed, indicating that the enhanced membrane affinity may be
      attributed to intercellular membrane differences. 

PMID- 25873451
TI  - The Case for Individualized Goal Attainment Scaling Measurement in Elder Abuse
      Interventions.
AB  - Research available to inform the development of effective community-based elder
      abuse protective response interventions is severely limited. Elder abuse
      intervention research is constrained by a lack of research capacity, including
      sensitive and responsive outcome measures that can assess change in case status
      over the course of intervention. Given the heterogeneous nature of elder abuse,
      standard scales can lack the flexibility necessary to capture the diverse range
      of individually relevant issues across cases. In this paper, we seek to address
      this gap by proposing the adaptation and use of an innovative measurement
      strategy-goal attainment scaling-in the context of elder protection. Goal
      attainment scaling is an individualized, client-centered outcome measurement
      approach that has the potential to address existing measurement challenges
      constraining progress in elder abuse intervention research.

PMID- 25873452
TI  - Compensatory Strategies: Prevalence of Use and Relationship to Physical Function
      and Well-Being.
AB  - We examine prevalence of four compensatory strategies (assistive devices,
      receiving help, changing frequency, or method of performance) and their immediate
      and long-term relationship to well-being. A total of 319 older adults (>70 years)
      with functional difficulties at home provided baseline data; 285 (89%) provided
      12-month data. For 17 everyday activities, the most frequently used strategy was
      changing method of performance ( M = 10.27 activities), followed by changing
      frequency ( M = 6.17), assistive devices ( M = 5.38), and receiving help ( M =
      3.37; p = .001). Using each strategy type was associated with functional
      difficulties at baseline ( ps < .0001), whereas each strategy type except
      changing method predicted functional decline 12 months later ( ps < .0001).
      Changing frequency of performing activities was associated with depressed mood (
      p < .0001) and poor mastery ( p < .0001) at both baseline and 12 months ( ps <
      .02). Findings suggest that strategy type may be differentially associated with
      functional decline and well-being although reciprocal causality and the role of
      other factors in these outcomes cannot be determined from this study.

PMID- 25873453
TI  - Older Adult Strategies for Community Wayfinding.
AB  - Community wayfinding becomes more challenging with age and decrements in
      functioning. Given the growth in numbers of older adults, we need to understand
      features that facilitate or inhibit wayfinding in outdoor settings to enhance
      mobility and community engagement. This exploratory study of 35 short- ( n = 14)
      and long-term ( n = 21) residents in an ethnically diverse neighborhood
      identified relevant wayfinding factors. Data collection included an interview,
      map-drawing task, and walk along a previously audited, prescribed route to
      identify key wayfinding strategies. Most participants sought information from
      other people as a primary method of route planning. Street signs and landmarks
      were overwhelming favorites as helpful wayfinding features. When asked to recall
      the route following the walk, only half of participants gave completely correct
      directions. Findings reinforce the importance of landmarks and legible,
      systematic, and consistently available signage, as well as trustworthy person-to
      person information sources. Findings also underscore the need for wayfinding
      research in diverse environments.

PMID- 25873454
TI  - Adopting Evidence-Based Caregiver Training Programs in the Real World: Outcomes
      and Lessons Learned From the STAR-C Oregon Translation Study.
AB  - OBJECTIVES: This article describes the translation and evaluation of STAR
      Community Consultants program (STAR-C), an evidence-based dementia caregiver
      training program, within the Oregon Department of Human Services. METHOD: Staff
      from two regional Area Agencies on Aging (AAAs) were trained to implement all
      aspects of STAR-C, including screening, recruitment of caregiver/care-receiver
      dyads, and treatment delivery. Mailed assessments of caregiver depression,
      burden, and care-receiver mood, behavior, and quality of life were collected at
      pre-treatment, post-treatment, and 6-month follow-up. RESULTS: One hundred fifty
      one dyads entered the program; 96 completed the 8-week intervention. Significant
      positive post-treatment effects were obtained for caregiver depression, burden,
      and reactivity to behavior problems, and care-receiver depression and quality of
      life. At 6-month follow-up, improvements in caregiver reactivity and care
      receiver depression were maintained. Caregivers reported high levels of
      satisfaction with the program. DISCUSSION: STAR-C was successfully and
      effectively implemented by participating AAAs. Recommendations for replication,
      including training, recruitment, and assessment procedures are provided.

PMID- 25873455
TI  - Phase I trial of active specific immunotherapy with autologous dendritic cells
      pulsed with autologous irradiated tumor stem cells in hepatitis B-positive
      patients with hepatocellular carcinoma.
AB  - BACKGROUND AND OBJECTIVES: Hepatocellular carcinoma (HCC) is often associated
      with chronic hepatitis due to hepatitis-B or -C viruses. Active specific
      immunotherapy (ASI) with autologous dendritic cells (DC) presenting antigens from
      autologous tumor stem cell (TC) lines is associated with promising long-term
      survival in metastatic cancer, but hepatitis patients were excluded. ASI might
      benefit high-risk primary HCC patients following surgical resection, but first it
      is important to show that ASI does not exacerbate hepatitis. METHODS: Previously
      untreated HCC patients with a solitary lesion > 5 cm, or three lesions with at
      least one > 3 cm, or more than three lesions, underwent surgical resection from
      which autologous TC lines were established. Irradiated TC were incubated with
      autologous DC to create DC-TC. After one course of trans-arterial
      chemoembolization therapy (TACE), three weekly subcutaneous injections of DC-TC
      suspended in granulocyte-macrophage colony stimulating factor were administered.
      Patients were monitored for eight weeks. RESULTS: HCC cell lines were established
      within five weeks for 15/15 patients. Eight patients, all with chronic hepatitis
      B, were treated. There was no increase in hepatic transaminases, hepatitis B
      antigens, or viral DNA. CONCLUSION: Autologous DC-TC did not exacerbate HBV in
      these HCC patients. A phase II efficacy trial is being planned.

PMID- 25873456
TI  - Potential metabolic strategies of widely distributed holobionts in the oceanic
      archipelago of St Peter and St Paul (Brazil).
AB  - Sponges are one of the most complex symbiotic communities and while the taxonomic
      composition of associated microbes has been determined, the biggest challenge now
      is to uncover their functional role in symbiosis. We investigated the microbiota
      of two widely distributed sponge species, regarding both their taxonomic
      composition and their functional roles. Samples of Didiscus oxeata and Scopalina
      ruetzleri were collected in the oceanic archipelago of St Peter and St Paul and
      analysed through metagenomics. Sequences generated by 454 pyrosequencing and Ion
      Torrent were taxonomically and functionally annotated on the MG-RAST server using
      the GenBank and SEED databases, respectively. Both communities exhibit
      equivalence in core functions, interestingly played by the most abundant taxa in
      each community. Conversely, the microbial communities differ in composition,
      taxonomic diversity and potential metabolic strategies. Functional annotation
      indirectly suggests differences in preferential pathways of carbon, nitrogen and
      sulphur metabolisms, which may indicate different metabolic strategies.

PMID- 25873457
TI  - Measuring bacterial activity and community composition at high hydrostatic
      pressure using a novel experimental approach: a pilot study.
AB  - In this pilot study, we describe a high-pressure incubation system allowing
      multiple subsampling of a pressurized culture without decompression. The system
      was tested using one piezophilic (Photobacterium profundum), one piezotolerant
      (Colwellia maris) bacterial strain and a decompressed sample from the
      Mediterranean deep sea (3044 m) determining bacterial community composition,
      protein production (BPP) and cell multiplication rates (BCM) up to 27 MPa. The
      results showed elevation of BPP at high pressure was by a factor of 1.5 +/- 1.4
      and 3.9 +/- 2.3 for P. profundum and C. maris, respectively, compared to ambient
      pressure treatments and by a factor of 6.9 +/- 3.8 fold in the field samples. In
      P. profundum and C. maris, BCM at high pressure was elevated (3.1 +/- 1.5 and 2.9
      +/- 1.7 fold, respectively) compared to the ambient-pressure treatments. After 3
      days of incubation at 27 MPa, the natural bacterial deep-sea community was
      dominated by one phylum of the genus Exiguobacterium, indicating the rapid
      selection of piezotolerant bacteria. In future studies, our novel incubation
      system could be part of an isopiestic pressure chain, allowing more accurate
      measurement of bacterial activity rates which is important both for modeling and
      for predicting the efficiency of the oceanic carbon pump. 

PMID- 25873459
TI  - Changes of soil bacterial communities in bamboo plantations at different
      elevations.
AB  - The effect of altitude on the distribution of plants and animals has been well
      studied. In contrast, the response of microbes to elevation is poorly understood.
      To determine whether soil bacterial communities respond to altitudinal gradients,
      moso bamboo forest soils along a gradient of six elevations from 600 to 1800 m
      were investigated using the barcoded pyrosequencing method. The results revealed
      that Acidobacteria and Proteobacteria predominated in the six communities,
      although the relative abundances were different. Non-metric multidimensional
      scaling analysis with the abundant OTUs showed that the community composition
      possessed a complex relationship with elevation. The communities at 1000 and 1200
      m were similar and possessed higher levels of diversity than the communities at
      both lower and higher elevations, giving the diversity a hump-backed trend with
      elevation. By contrast, the soil C and N and microbial biomass properties
      increased linearly with elevation. Thus, the complex response of the bacterial
      community composition and diversity across elevation could not be explained as a
      simple response to elevation and presumably results from interactions between
      multiple factors such as soil organic matter content and temperature. 

PMID- 25873460
TI  - Seasonal variations of marine protist community structure based on taxon-specific
      traits using the eastern English Channel as a model coastal system.
AB  - Previous microscopy-based studies in the eastern English Channel have revealed it
      to be a productive meso-eutrophic coastal ecosystem, characterized by strong
      repeating patterns in microplankton succession. The present study examines the
      seasonal structure of the entire protistan community from March 2011 to July
      2013, using tag pyrosequencing of the V2-V3 hypervariable region of the 18S rRNA
      gene. A total of 1242 OTUs and 28 high-level taxonomic groups, which included
      previously undetected taxa in the area, were identified. The detected OTUs were
      considered according to taxon-specific traits, which included their trophic role,
      abundance and specialization level. Taxa differentiation based on specialization
      level rather than abundance was more informative in describing community
      organization. While generalists were always abundant, numerous specialists that
      were either rare or absent in most samples, increased in abundance for short
      periods, appearing to be overall abundant. Statistical and network analyses
      showed that the protistan seasonal organization was influenced by environmental
      parameters. It also highlighted that in addition to grazers, fungi and parasites
      played potentially significant roles during phytoplankton blooms. Overall, while
      the protistan succession was mainly shaped by environmental variations, biotic
      interactions among co-occurring taxa were the main structural drivers of the
      temporal assemblages. 

PMID- 25873458
TI  - Linking fungal communities to wood density loss after 12 years of log decay.
AB  - Changes in biodiversity might alter decomposition processes and, consequently,
      carbon and nutrient cycling. We examined fungal diversity and density loss in
      experimental Norway spruce logs after 12 years of decay in a hemiboreal forest.
      Between 28 and 50% of the original wood biomass remained, depending on the fungal
      community composition in the log, operational taxonomic unit (OTU) richness had
      only a minor effect on the log biomass. Although the communities were OTU rich
      (190-340 OTUs per log), the majority of OTUs were infrequent or rare; wood
      degradation therefore depended mostly on the most abundant OTUs and their
      decomposing abilities. The least decayed logs were characterized by continuous
      dominance of an earlier colonizer and by high within-log community diversity,
      which was significantly related to sample variables (position in log, density and
      moisture). In the most decayed logs, the earlier colonizers were generally
      replaced by white-rot species able to exploit the highly decomposed wood. The
      communities were relatively spatially uniform within whole logs, independent of
      the sample variables, whereas among-log diversity was high. Importance of fungal
      community composition in decomposition processes should be taken into account
      when studying and modeling carbon dynamics in forest ecosystems. 

PMID- 25873461
TI  - Anaerobic alkane biodegradation by cultures enriched from oil sands tailings
      ponds involves multiple species capable of fumarate addition.
AB  - A methanogenic short-chain alkane-degrading culture (SCADC) was enriched from oil
      sands tailings and transferred several times with a mixture of C6, C7, C8 and C10
      n-alkanes as the predominant organic carbon source, plus 2-methylpentane, 3
      methylpentane and methylcyclopentane as minor components. Cultures produced ~40%
      of the maximum theoretical methane during 18 months incubation while depleting
      the n-alkanes, 2-methylpentane and methylcyclopentane. Substrate depletion
      correlated with detection of metabolites characteristic of fumarate activation of
      2-methylpentane and methylcyclopentane, but not n-alkane metabolites. During
      active methanogenesis with the mixed alkanes, reverse-transcription PCR confirmed
      the expression of functional genes (assA and bssA) associated with hydrocarbon
      addition to fumarate. Pyrosequencing of 16S rRNA genes amplified during active
      alkane degradation revealed enrichment of Clostridia (particularly
      Peptococcaceae) and methanogenic Archaea (Methanosaetaceae and
      Methanomicrobiaceae). Methanogenic cultures transferred into medium containing
      sulphate produced sulphide, depleted n-alkanes and produced the corresponding
      succinylated alkane metabolites, but were slow to degrade 2-methylpentane and
      methylcyclopentane; these cultures were enriched in Deltaproteobacteria rather
      than Clostridia. 3-Methylpentane was not degraded by any cultures. Thus,
      nominally methanogenic oil sands tailings harbour dynamic and versatile
      hydrocarbon-degrading fermentative syntrophs and sulphate reducers capable of
      degrading n-, iso- and cyclo-alkanes by addition to fumarate. 

PMID- 25873462
TI  - Community priming--effects of sequential stressors on microbial assemblages.
AB  - Microbes in nature are exposed to complex environmental stressors which challenge
      their functioning or survival. Priming is the improved reaction of an organism to
      an environmental stressor following a preceding, often milder stress event. This
      phenomenon, also known as cross-protection, predictive response strategy or
      acquired stress resistance, is becoming an increasingly well-established research
      topic in microbiology, which has so far been examined from the perspective of a
      single organism or population. However, microbes in nature occur as part of
      communities; thus it is timely to highlight the need to also include this level
      beyond the individual species in studies of priming effects. We here introduce a
      conceptual framework for such studies at the level of the microbial assemblage
      and also chart a way forward for empirical and theoretical study. We illustrate
      some of the elements of our framework with a simple simulation model. Given the
      dynamic habitat of many microbes, incorporating priming is important for a more
      complete understanding of microbial community responses to stress. 

PMID- 25873463
TI  - Iron supply constrains producer communities in stream ecosystems.
AB  - The current paradigm that stream producers are under exclusive macronutrient
      control was recently challenged by continental studies, demonstrating that iron
      supply constrained diatom biodiversity and energy flows. Using algal abundance
      and water chemistry data from the National Water-Quality Assessment Program, we
      determined for the first time community thresholds along iron gradients in non
      acidic running waters, i.e. 30-79.5 MUg L(-1) and 70-120 MUg L(-1) in
      oligotrophic and eutrophic streams, respectively. Given that Fe concentrations
      fell below both thresholds in 50% of US streams, and below the eutrophic
      threshold in 75% of US streams, we suggest that Fe limitation is potentially
      widespread and attribute it to the restricted distribution of wetlands. We also
      report results from the first laboratory experiments on algal-iron interactions
      in streams, revealing that iron supplementation leads to significant biovolume
      and biodiversity increase in both nitrogen fixing and non-nitrogen fixing algae.
      Therefore, the progressive brownification of freshwaters due to rising dissolved
      organic carbon and iron levels can have a stimulating influence on microbial
      producers with cascading effects along the trophic hierarchy. Future research in
      running waters should focus on the role of iron in algal physiology and biofilm
      functions, including accumulation of biomass, fixing atmospheric nitrogen and
      improving water quality. 

PMID- 25873464
TI  - Gene expression profiles of Vibrio parahaemolyticus in viable but non-culturable
      state.
AB  - Viable but non-culturable (VBNC) state is referred to as a dormant state of non
      sporulating bacteria enhancing the survival in adverse environments. To our
      knowledge, only few studies have been conducted on whole genomic expression of
      Vibrio parahaemolyticus VBNC state. Since a degradation of nucleic acids in V.
      vulnificus non-culturable state has been detected, we hypothesize that gene
      regulation of VBNC cells is highly reduced, downregulation of gene expression is
      dominant and only metabolic functions crucial for survival are kept on a
      sustained basis. Hence, we performed the whole transcriptomic profiles of V.
      parahaemolyticus in three phases (exponential, early stationary phase and VBNC
      state). Compared with exponential and early stationary phase, in V.
      parahaemolyticus VBNC cells we found 509 induced genes and 309 repressed by more
      than 4-fold among 4820 investigated genes. Upregulation was dominant in most of
      non-metabolism functional categories, while five metabolism-related functional
      categories revealed downregulation in VBNC state. To our knowledge, this is the
      first study of comprehensive transcriptomic analyses of three phases of V.
      parahaemolyticus RIMD2210633. Although the mechanism of VBNC state is not yet
      clear, massive regulation of gene expression occurs in VBNC state compared with
      expression in other two phases, indicating VBNC cells are active. 

PMID- 25873465
TI  - Physiological and evolutionary potential of microorganisms from the Canterbury
      Basin subseafloor, a metagenomic approach.
AB  - Subseafloor sediments represent a large reservoir of organic matter and are
      inhabited by microbial groups of the three domains of life. Besides impacting the
      planetary geochemical cycles, the subsurface biosphere remains poorly understood,
      notably questions related to possible metabolic pathways and selective advantages
      that may be deployed by buried microorganisms (sporulation, response to stress,
      dormancy). In order to better understand physiological potentials and possible
      lifestyles of subseafloor microbial communities, we analyzed two metagenomes from
      subseafloor sediments collected at 31 mbsf (meters below the sea floor) and 136
      mbsf in the Canterbury Basin. Metagenomic phylogenetic and functional diversities
      were very similar. Phylogenetic diversity was mostly represented by Chloroflexi,
      Firmicutes and Proteobacteria for Bacteria and by Thaumarchaeota and
      Euryarchaeota for Archaea. Predicted anaerobic metabolisms encompassed
      fermentation, methanogenesis and utilization of fatty acids, aromatic and
      halogenated substrates. Potential processes that may confer selective advantages
      for subsurface microorganisms included sporulation, detoxication equipment or
      osmolyte accumulation. Annotation of genomic fragments described the metabolic
      versatility of Chloroflexi, Miscellaneous Crenarchaeotic Group and Euryarchaeota
      and showed frequent recombination events within subsurface taxa. This study
      confirmed that the subseafloor habitat is unique compared to other habitats at
      the (meta)-genomic level and described physiological potential of still
      uncultured groups. 

PMID- 25873466
TI  - DNA stable-isotope probing of oil sands tailings pond enrichment cultures reveals
      different key players for toluene degradation under methanogenic and sulfidogenic
      conditions.
AB  - Oil sands tailings ponds are anaerobic repositories of fluid wastes produced by
      extraction of bitumen from oil sands ores. Diverse indigenous microbiota
      biodegrade hydrocarbons (including toluene) in situ, producing methane, carbon
      dioxide and/or hydrogen sulfide, depending on electron acceptor availability.
      Stable-isotope probing of cultures enriched from tailings associated specific
      taxa and functional genes to (13)C6- and (12)C7-toluene degradation under
      methanogenic and sulfate-reducing conditions. Total DNA was subjected to
      isopycnic ultracentrifugation followed by gradient fraction analysis using
      terminal restriction fragment length polymorphism (T-RFLP) and construction of
      16S rRNA, benzylsuccinate synthase (bssA) and dissimilatory sulfite reductase
      (dsrB) gene clone libraries. T-RFLP analysis plus sequencing and in silico
      digestion of cloned taxonomic and functional genes revealed that Clostridiales,
      particularly Desulfosporosinus (136 bp T-RF) contained bssA genes and were key
      toluene degraders during methanogenesis dominated by Methanosaeta.
      Deltaproteobacterial Desulfobulbaceae (157 bp T-RF) became dominant under
      sulfidogenic conditions, likely because the Desulfosporosinus T-RF 136 apparently
      lacks dsrB and therefore, unlike its close relatives, is presumed incapable of
      dissimilatory sulfate reduction. We infer incomplete oxidation of toluene by
      Desulfosporosinus in syntrophic association with Methanosaeta under methanogenic
      conditions, and complete toluene oxidation by Desulfobulbaceae during sulfate
      reduction. 

PMID- 25873467
TI  - Resilience and adjustments of surface sediment bacterial communities in an
      enclosed shallow coastal lagoon, Magdalen Islands, Gulf of St. Lawrence, Canada.
AB  - Bacteria regulate global biogeochemical cycles and much of this activity occurs
      in shallow coastal sediments; however, little is known of the seasonality or how
      changes in environmental conditions influence the active sediment bacterial
      communities. Havre-aux-Maisons (Magdalen Islands, Canada), a relatively pristine
      enclosed shallow coastal lagoon, is of particular biological interest since it
      has no inflowing rivers and provides an opportunity to investigate non-estuarine
      shallow marine sediments. Potentially active taxa in surface sediments were
      identified over a 15-month period using high-throughput rRNA amplicon sequencing.
      Sediment bacterial communities were diverse at the species level, with high Beta
      diversity. Throughout most of the sampling period, communities consisted of taxa
      that were closely related to each other, suggesting that specific environmental
      conditions at a given time point favored taxa with similar ecological traits.
      However, bacterial phyla and proteobacterial classes were remarkably similar over
      time with a predominantly sulfur cycling community composed of sulfur-oxidizing
      Gammaproteobacteria and sulfate-reducing Deltaproteobacteria persisting over much
      of the sampling period, despite the oxygenated water column. This community was
      disrupted after a storm and less common phyla became relatively more abundant.
      Following this disruption, a high proportion of benthic Cyanobacteria colonized
      the sediment before the reestablishment of the sulfur-cycle-dominated community. 

PMID- 25873468
TI  - Size-fractionated diversity of eukaryotic microbial communities in the Eastern
      Tropical North Pacific oxygen minimum zone.
AB  - Oxygen minimum zones (OMZs) caused by water column stratification appear to
      expand in parts of the world's ocean, with consequences for marine biogeochemical
      cycles. OMZ formation is often fueled by high surface primary production, and
      sinking organic particles can be hotspots of interactions and activity within
      microbial communities. This study investigated the diversity of OMZ protist
      communities in two biomass size fractions (>30 and 30-1.6 MUm filters) from the
      world's largest permanent OMZ in the Eastern Tropical North Pacific. Diversity
      was quantified via Illumina MiSeq sequencing of V4 region of 18S SSU rRNA genes
      in samples spanning oxygen gradients at two stations. Alveolata and Rhizaria
      dominated the two size fractions at both sites along the oxygen gradient.
      Community composition at finer taxonomic levels was partially shaped by oxygen
      concentration, as communities associated with versus anoxic waters shared only
      ~32% of operational taxonomic unit (OTU) (97% sequence identity) composition.
      Overall, only 9.7% of total OTUs were recovered at both stations and under all
      oxygen conditions sampled, implying structuring of the eukaryotic community in
      this area. Size-fractionated communities exhibited different taxonomical features
      (e.g. Syndiniales Group I in the 1.6-30 MUm fraction) that could be explained by
      the microniches created on the surface-originated sinking particles. 

PMID- 25873469
TI  - Phylogenetic structure of soil bacterial communities predicts ecosystem
      functioning.
AB  - Quantifying diversity with phylogeny-informed metrics helps understand the
      effects of diversity on ecosystem functioning (EF). The sign of these effects
      remains controversial because phylogenetic diversity and taxonomic identity may
      interactively influence EF. Positive relationships, traditionally attributed to
      complementarity effects, seem unimportant in natural soil bacterial communities.
      Negative relationships could be attributed to fitness differences leading to the
      overrepresentation of few productive clades, a mechanism recently invoked to
      assemble soil bacteria communities. We tested in two ecosystems contrasting in
      terms of environmental heterogeneity whether two metrics of phylogenetic
      community structure, a simpler measure of phylogenetic diversity (NRI) and a more
      complex metric incorporating taxonomic identity (PCPS), correctly predict
      microbially mediated EF. We show that the relationship between phylogenetic
      diversity and EF depends on the taxonomic identity of the main coexisting
      lineages. Phylogenetic diversity was negatively related to EF in soils where a
      marked fertility gradient exists and a single and productive clade
      (Proteobacteria) outcompete other clades in the most fertile plots. However,
      phylogenetic diversity was unrelated to EF in soils where the fertility gradient
      is less marked and Proteobacteria coexist with other abundant lineages. Including
      the taxonomic identity of bacterial lineages in metrics of phylogenetic community
      structure allows the prediction of EF in both ecosystems. 

PMID- 25873470
TI  - Increased prevalence of EPAS1 variant in cattle with high-altitude pulmonary
      hypertension.
AB  - High-altitude pulmonary hypertension (HAPH) has heritable features and is a major
      cause of death in cattle in the Rocky Mountains, USA. Although multiple genes are
      likely involved in the genesis of HAPH, to date no major gene variant has been
      identified. Using whole-exome sequencing, we report the high association of an
      EPAS1 (HIF2alpha) double variant in the oxygen degradation domain of EPAS1 in
      Angus cattle with HAPH, mean pulmonary artery pressure >50 mm Hg in two
      independent herds. Expression analysis shows upregulation of 26 of 27 HIF2alpha
      target genes in EPAS1 carriers with HAPH. Of interest, this variant appears to be
      prevalent in lowland cattle, in which 41% of a herd of 32 are carriers, but the
      variant may only have a phenotype when the animal is hypoxemic at altitude. The
      EPAS1 variant will be a tool to determine the cells and signalling pathways
      leading to HAPH. 

PMID- 25873471
TI  - X-ray Angiography Perfusion Analysis for the Balloon Occlusion Test of the
      Internal Carotid Artery.
AB  - BACKGROUND: A perfusion study should be performed during the balloon occlusion
      test (BOT) to prevent ischemic events after therapeutic carotid occlusion. We
      evaluated the efficacy of X-ray angiography perfusion analysis during the BOT.
      METHODS: Twenty-one consecutive patients who underwent the BOT of the internal
      carotid artery were included. Patients who had a venous phase delay of less than
      .5 seconds and a mean stump pressure of more than 50 mm Hg without any neurologic
      symptoms were considered tolerant, and other patients were considered intolerant.
      A time-density curve was constructed for each hemisphere using X-ray angiography
      perfusion software (2D-Perfusion). The mean transit time and area under the
      curve, which correspond to cerebral blood volume, were calculated from the curve.
      Differences in these parameters between the occluded and nonoccluded hemispheres
      and the perfusion index were compared between the tolerant and intolerant groups.
      RESULTS: In the intolerant group, the mean transit time was significantly longer
      (1.31 +/- .72 seconds versus .44 +/- .21 seconds, P = .001) and the perfusion
      index was significantly lower (.72 +/- .16 versus .94 +/- .08, P = .001) compared
      with those in the tolerant group. The area under the curve was not different
      between the groups. CONCLUSIONS: Parameters obtained by X-ray angiography
      perfusion analysis were significantly different between the tolerant and
      intolerant groups. The X-ray angiography perfusion analysis could be a safe and
      effective method for assessing ischemic tolerance before therapeutic carotid
      occlusion.

PMID- 25873472
TI  - Blood Pressure Variability and Clinical Outcome in Patients with Acute
      Intracerebral Hemorrhage.
AB  - BACKGROUND: The aim of this study was to evaluate whether fluctuations of blood
      pressure (BP) levels occurring in the acute stage of spontaneous intracerebral
      hemorrhage (ICH) affect the 3-month clinical outcome. METHODS: We retrospectively
      identified consecutive patients hospitalized for acute spontaneous ICH. BP
      measurements over the first 72 hours from the onset of symptoms were recorded,
      and standard deviation (SD), coefficient of variation (CV), and maximum-minimum
      difference (max-min) were determined to characterize both systolic and diastolic
      BP variability (BPV). The measure of outcome was the 3-month functional status
      assessed by the modified Rankin Scale following a baseline severity-adjusted
      analysis. RESULTS: Among the 138 enrolled patients with ICH, 67 (48.6%) were
      classified as having a poor 3-month functional recovery. A dose-response
      relationship with poor outcome was found for each measure of systolic BPV-
      adjusted odds ratios (ORs) for the highest thirds of SD 7.95 (95% confidence
      interval [CI], 2.88-21.90), CV 7.74 (95% CI, 2.88-20.80), and max-min 8.36 (95%
      CI, 2.72-25.62; P < .001). The strength of association with diastolic BPV turned
      out to be weaker and significant only for the higher values (adjusted ORs for the
      highest thirds of SD 6.74 [95% CI, 2.52-18.04], CV 4.57 [95% CI, 1.77-11.81], and
      max-min 4.34 [95% CI, 1.72-10.93]). CONCLUSIONS: In patients with acute ICH, BPV
      was a strong predictor of the 3-month clinical outcome and may represent a still
      neglected potential therapeutic target.

PMID- 25873474
TI  - Laser induced SERS switching using plasmonic heating of PNIPAM coated HGNs.
AB  - This is the first report of SERS switching 'on and off' using laser induced
      plasmonic heating of poly(N-isopropylacrylamide) (PNIPAM) coated hollow gold
      nanoshells (HGNs). The degree of Raman enhancement for these thermosensitive SERS
      nanotags was controlled by plasmonic tuning of the properties of the HGNs. 

PMID- 25873473
TI  - Telemedical Brain Computed Tomography Misinterpretation by Stroke Neurologists Is
      Not Associated with Thrombolysis-Related Intracranial Hemorrhage.
AB  - BACKGROUND: The Stroke Eastern Saxony Network (SOS-NET) provides telecare for
      acute stroke patients. Stroke neurologists recommend intravenous thrombolysis
      based on clinical assessment and cerebral computed tomography (CT) evaluation
      using Alberta Stroke Program Early CT score (ASPECTS). We sought to assess
      whether ASPECTS misinterpretation by stroke neurologists was associated with
      thrombolysis-related symptomatic intracranial hemorrhage (sICH). METHODS: We
      retrospectively analyzed consecutive SOS-NET patients treated with thrombolytics
      from July 2007 to July 2012. Experienced neuroradiologists re-evaluated CT scans
      blinded to clinical information providing reference standard. We defined ASPECTS
      underestimation as ASPECTS stroke neurologist--ASPECTS neuroradiologist more than
      1 point. Primary outcome was sICH by European Cooperative Acute Stroke Study II
      criteria. Secondary outcome was unfavorable outcome at discharge defined as
      modified Rankin Scale scores 3 or more. RESULTS: Of 1659 patients with acute
      ischemic stroke, thrombolysis was performed in 657 patients. Complete primary
      outcome and imaging data were available for 432 patients (median age, 75;
      interquartile range [IQR], 12 years; National Institutes of Health Stroke Scale
      score, 12 [IQR, 11]; 52.8% women). Nineteen patients (4.4%) had sICH, and 259
      patients (60.0%) had an unfavorable outcome at discharge. Interobserver agreement
      between ASPECTS assessment was fair (kappa = .51). ASPECTS underestimation was
      neither associated with sICH (adjusted odds ratio (OR), 1.32; 95% confidence
      interval (CI), .36-4.83, P = .68) nor unfavorable outcome (adjusted OR, 1.10; 95%
      CI, .47-2.54; P = .83). CONCLUSIONS: Despite fair interrater agreement between
      stroke neurologists and expert neuroradiologists, underestimation of ASPECTS by
      the former was not associated with thrombolysis-related sICH in our telestroke
      network.

PMID- 25873475
TI  - Reliable simultaneous zymographic method of characterization of cellulolytic
      enzymes from fungal cellulase complex.
AB  - A method for zymographic detection of specific cellulases in a complex
      (endocellulase, exocellulase, and cellobiase) from crude fermentation extracts,
      after a single electrophoretic separation, is described in this paper. Cellulases
      were printed onto a membrane and, subsequently, substrate gel. Cellobiase
      isoforms were detected on the membrane using esculine as substrate, endocellulase
      isoforms on substrate gel with copolymerized carboxymethyl cellulose (CMC), while
      exocellulase isoforms were detected in electrophoresis gel with 4
      methylumbelliferyl-beta-d-cellobioside (MUC). This can be a useful additional
      tool for monitoring and control of fungal cellulase production in industrial
      processes and fundamental research, screening for particular cellulase producers,
      or testing of new lignocellulose substrates. 

PMID- 25873477
TI  - Surfactant-free synthesis of plasmonic tungsten oxide nanowires with visible
      light-enhanced hydrogen generation from ammonia borane.
AB  - WO3-x nanowires were successfully synthesized through a simple surfactant-free
      solvothermal method. These nanowires exhibit strong plasmonic absorption in the
      visible and near-infrared region owing to the abundant oxygen vacancies. The
      plasmon excitation of these WO3-x nanowires provide five times enhancement on the
      hydrogen generation from ammonia borane. 

PMID- 25873476
TI  - Feasibility of extended ambulatory electrocardiogram monitoring to identify
      silent atrial fibrillation in high-risk patients: the Screening Study for
      Undiagnosed Atrial Fibrillation (STUDY-AF).
AB  - BACKGROUND: Identification of silent atrial fibrillation (AF) could prevent
      stroke and other sequelae. HYPOTHESIS: Screening for AF using continuous
      ambulatory electrocardiographic (ECG) monitoring can detect silent AF in
      asymptomatic in patients with known risk factors. METHODS: We performed a single
      center prospective screening study using a wearable patch-based device that
      provides up to 2 weeks of continuous ambulatory ECG monitoring (iRhythm
      Technologies, Inc.). Inclusion criteria were age >=55 years and >=2 of the
      following risk factors: coronary disease, heart failure, hypertension, diabetes,
      sleep apnea. We excluded patients with prior AF, stroke, transient ischemic
      attack, implantable pacemaker or defibrillator, or with palpitations or syncope
      in the prior year. RESULTS: Out of 75 subjects (all male, age 69 +/- 8.0 years;
      ejection fraction 57% +/- 8.7%), AF was detected in 4 subjects (5.3%; AF burden
      28% +/- 48%). Atrial tachycardia (AT) was present in 67% (>=4 beats), 44% (>=8
      beats), and 6.7% (>=60 seconds) of subjects. The combined diagnostic yield of
      sustained AT/AF was 11%. In subjects without sustained AT/AF, 11 (16%) had >=30
      supraventricular ectopic complexes per hour. CONCLUSIONS: Outpatient extended ECG
      screening for asymptomatic AF is feasible, with AF identified in 1 in 20 subjects
      and sustained AT/AF identified in 1 in 9 subjects, respectively. We also found a
      high prevalence of asymptomatic AT and frequent supraventricular ectopic
      complexes, which may be relevant to development of AF or stroke. If confirmed in
      a larger study, primary screening for AF could have a significant impact on
      public health.

PMID- 25873478
TI  - Nursing students' perceptions of factors influencing their learning environment
      in a clinical skills laboratory: A qualitative study.
AB  - BACKGROUND: The mastery of clinical skills learning is required to become a
      trained nurse. Due to limited opportunities for clinical skills training in
      clinical practice, undergraduate training at clinical skills laboratories (CSLs)
      is an essential part of nursing education. In a sociocultural learning
      perspective learning is situated in an environment. Growing student cohorts,
      rapid introduction of technology-based teaching methods and a shift from a
      teaching- to a learning-centered education all influence the environment of the
      students. These changes also affect CSLs and therefore compel nursing faculties
      to adapt to the changing learning environment. OBJECTIVES: This study aimed to
      explore students' perceptions of their learning environment in a clinical skills
      laboratory, and to increase the knowledge base for improving CSL learning
      conditions identifying the most important environmental factors according to the
      students. DESIGN: An exploratory qualitative methodology was used. PARTICIPANTS:
      Nineteen second-year students enrolled in an undergraduate nursing program in
      Norway participated in the study. They took the same clinical skills course.
      Eight were part-time students (group A) and 11 were full-time students (group B).
      METHODS: Focus group interviews and content analysis were conducted to capture
      the students' perception of the CSL learning environment. RESULTS: The study
      documents students' experience of the physical (facilities, material equipment,
      learning tools, standard procedures), psychosocial (expectations, feedback,
      relations) and organizational (faculty resources, course structure) factors that
      affect the CSL learning environment. CONCLUSION: Creating an authentic
      environment, facilitating motivation, and providing resources for multiple
      methods and repetitions within clinical skills training are all important for
      improving CSL learning environments from the student perspective.

PMID- 25873479
TI  - Switching bipolar hepatic radiofrequency ablation using internally cooled wet
      electrodes: comparison with consecutive monopolar and switching monopolar modes.
AB  - OBJECTIVE: To evaluate whether switching bipolar radiofrequency ablation (SB-RFA)
      using three internally cooled wet (ICW) electrodes can induce coagulations >5 cm
      in porcine livers with better efficiency than consecutive monopolar (CM) or
      switching monopolar (SM) modes. METHODS: A total of 60 coagulations were made in
      15 in vivo porcine livers using three 17-gauge ICW electrodes and a multichannel
      radiofrequency (RF) generator. RF energy (approximately 200 W) was applied in CM
      mode (Group A, n = 20) for 24 min, SM mode for 12 min (Group B, n = 20) or
      switching bipolar (SB) mode for 12 min (Group C, n = 20) in in vivo porcine
      livers. Thereafter, the delivered RFA energy, as well as the shape and dimension
      of coagulations were compared among the groups. RESULTS: Spherical- or oval
      shaped ablations were created in 30% (6/20), 85% (17/20) and 90% (18/20) of
      coagulations in the CM, SM and SB groups, respectively (p = 0.003). SB-RFA
      created ablations >5 cm in minimum diameter (Dmin) in 65% (13/20) of porcine
      livers, whereas SM- or CM-RFA created ablations >5 cm in only 25% (5/20) and 20%
      (4/20) of porcine livers, respectively (p = 0.03). The mean Dmin of coagulations
      was significantly larger in Group C than in Groups A and B (5.1 +/- 0.9, 3.9 +/-
      1.2 and 4.4 +/- 1.0 cm, respectively, p = 0.002) at a lower delivered RF energy
      level (76.8 +/- 14.3, 120.9 +/- 24.5 and 114.2 +/- 18.3 kJ, respectively, p <
      0.001). CONCLUSION: SB-RFA using three ICW electrodes can create coagulations >5
      cm in diameter with better efficiency than do SM- or CM-RFA. ADVANCES IN
      KNOWLEDGE: SB-RFA can create large, regular ablation zones with better time
      energy efficiency than do CM- or SM-RFA.

PMID- 25873480
TI  - Acute anal toxicity after whole pelvic radiotherapy in patients with asymptomatic
      haemorrhoids: identification of dosimetric and patient factors.
AB  - OBJECTIVE: Patients with asymptomatic haemorrhoids are known to be less tolerant
      of radiation doses lower than known tolerance doses. In the present study, the
      authors sought to identify the risk factors of acute haemorrhoid aggravation
      after whole pelvic radiotherapy (WPRT). METHODS: The records of 33 patients with
      cervical, rectal or prostate cancer with asymptomatic haemorrhoids, which were
      confirmed by colonoscopy before the start of radiotherapy (RT), were reviewed.
      Acute anal symptoms, such as anal pain and bleeding, were observed up to 1 month
      after RT completion. Dosimetric and patient factors were analysed, and subgroup
      analyses were performed. RESULTS: The median induction dose for acute anal
      symptoms was 34.1 Gy (range, 28.8-50.4 Gy). Post-operative treatment intent
      showed more acute anal toxicity of patient factors (p = 0.04). In subgroup
      analysis, post-operative treatment intent and concurrent chemoradiotherapy were
      found to be related to acute anal symptoms (p < 0.01). Of the dosimetric factors,
      V10 tended to be related to acute anal symptoms (p = 0.08). CONCLUSION: This
      study indicates that asymptomatic haemorrhoid may deteriorate after low-dose
      radiation and that patient factors, such as treatment intent and concurrent
      chemotherapy, probably influence anal toxicity. In patients with asymptomatic
      haemorrhoids, WPRT requires careful dosimetry and clinical attention. ADVANCES IN
      KNOWLEDGE: The tolerance of anal canal tends to be ignored in patients with
      pelvic cancer who are undergoing WPRT. However, patients with asymptomatic
      haemorrhoids may be troubled by low radiation doses, and further studies are
      required.

PMID- 25873481
TI  - LungTech, an EORTC Phase II trial of stereotactic body radiotherapy for centrally
      located lung tumours: a clinical perspective.
AB  - Evidence supports stereotactic body radiotherapy (SBRT) as a curative treatment
      option for inoperable early stage non-small-cell lung cancer (NSCLC) resulting in
      high rates of tumour control and low risk of toxicity. However, promising results
      are mainly derived from SBRT of peripheral pulmonary lesions, whereas SBRT for
      the central tumours can lead to severe radiation sequelae owing to the spatial
      proximity to the serial organs at risk. Robust data on the tolerance of
      mediastinal structures to high-dose hypofractionated radiation are limited;
      furthermore, there are many open questions regarding the efficiency, safety and
      response assessment of SBRT in inoperable, centrally located early stage NSCLC,
      which are addressed in a prospective multicentre study [sponsored by the European
      Organization for Research and Treatment of Cancer (EORTC 22113-08113-LungTech)].
      In this review, we summarize the current status regarding SBRT for centrally
      located early stage NSCLC that leads to the rationale of the LungTech trial.
      Outline and some essential features of the study with focus on a summary of
      current experiences in dose/fraction-toxicity coherences after SBRT to the
      mediastinal structures that lead to LungTech normal tissue constraints are
      provided. 

PMID- 25873483
TI  - Plasticity of the malleobactin pathway and its impact on siderophore action in
      human pathogenic bacteria.
AB  - The human pathogenic bacteria Burkholderia mallei, Burkholderia pseudomallei, and
      Burkholderia thailandensis harbor a highly conserved gene cluster coding for the
      biosynthesis of the long sought-after malleobactins. Four new, unexpected
      congeners of the malleobactin family that were isolated and fully characterized
      in this study feature unusual deviations from the parent, ornibactin-like
      architecture. Thus, the malleobactin non-ribosomal peptide synthetase (NRPS) has
      a rare flexibility that yields diverse peptide backbones, of which one candidate
      confers pronounced siderophore activity (EC50: 8.4 MUM, CAS assay). These
      findings not only unveil a highly diverse assembly line but also are an important
      addition to the knowledgebase of the pathogens' metabolomes.

PMID- 25873484
TI  - Focusing on infection prevention to slow antimicrobial resistance rates.

PMID- 25873482
TI  - Quantitative Proteomics of Human Fibroblasts with I1061T Mutation in Niemann-Pick
      C1 (NPC1) Protein Provides Insights into the Disease Pathogenesis.
AB  - Niemann-Pick type C (NPC) disease is a fatal neurodegenerative disorder
      characterized by the accumulation of unesterified cholesterol in the late
      endosomal/lysosomal compartments. Mutations in the NPC1 protein are implicated in
      95% of patients with NPC disease. The most prevalent mutation is the missense
      mutation I1061T that occurs in ~ 15-20% of the disease alleles. In our study, an
      isobaric labeling-based quantitative analysis of proteome of NPC1(I1061T) primary
      fibroblasts when compared with wild-type cells identified 281 differentially
      expressed proteins based on stringent data analysis criteria. Gene ontology
      enrichment analysis revealed that these proteins play important roles in diverse
      cellular processes such as protein maturation, energy metabolism, metabolism of
      reactive oxygen species, antioxidant activity, steroid metabolism, lipid
      localization, and apoptosis. The relative expression level of a subset of
      differentially expressed proteins (TOR4A, DHCR24, CLGN, SOD2, CHORDC1, HSPB7, and
      GAA) was independently and successfully substantiated by Western blotting. We
      observed that treating NPC1(I1061T) cells with four classes of seven different
      compounds that are potential NPC drugs increased the expression level of SOD2 and
      DHCR24. We have also shown an abnormal accumulation of glycogen in NPC1(I1061T)
      fibroblasts possibly triggered by defective processing of lysosomal alpha
      glucosidase. Our study provides a starting point for future more focused
      investigations to better understand the mechanisms by which the reported
      dysregulated proteins triggers the pathological cascade in NPC, and furthermore,
      their effect upon therapeutic interventions.

PMID- 25873485
TI  - NHANES 2009-2012 Findings: Association of Sexual Behaviors with Higher Prevalence
      of Oral Oncogenic Human Papillomavirus Infections in U.S. Men.
AB  - The incidence of human papillomavirus (HPV)-positive oropharyngeal cancers is
      higher and increasing more rapidly among men than women in the United States for
      unknown reasons. We compared the epidemiology of oral oncogenic HPV infection
      between men and women ages 14 to 69 years (N = 9,480) within the U.S. National
      Health and Nutritional Examination Surveys (NHANES) 2009-2012. HPV presence was
      detected in oral DNA by PCR. Analyses were stratified by gender and used NHANES
      sample weights. Oral oncogenic HPV prevalence was higher among men than women
      (6.6% vs. 1.5%, P < 0.001), corresponding to 7.07 million men versus 1.54 million
      women with prevalent infection at any point in time during 2009-2012. Prevalence
      increased significantly with age, current smoking, and lifetime number of sexual
      partners for both genders (adjusted Ptrend < 0.02). However, men had more
      partners than women (mean = 18 vs. 7, P < 0.001). Although oncogenic HPV
      prevalence was similar for men and women with 0 to 1 lifetime partners, the male
      female difference in prevalence significantly increased with number of lifetime
      partners (adjusted prevalence differences for none, 1, 2-5, 6-10, 11-20, and 20+
      partners = 1.0%, 0.5%, 3.0%, 5.7%, 4.6%, and 9.3%, respectively). Importantly,
      the per-sexual partner increase in prevalence was significantly stronger among
      men than among women (adjusted synergy index = 3.3; 95% confidence interval, 1.1
      9.7), and this increase plateaued at 25 lifetime partners among men versus 10
      partners among women. Our data suggest that the higher burden of oral oncogenic
      HPV infections and HPV-positive oropharyngeal cancers among men than women arises
      in part from higher number of lifetime sexual partners and stronger associations
      with sexual behaviors among men.

PMID- 25873487
TI  - A mixture hierarchical model for response times and response accuracy.
AB  - In real testing, examinees may manifest different types of test-taking
      behaviours. In this paper we focus on two types that appear to be among the more
      frequently occurring behaviours - solution behaviour and rapid guessing
      behaviour. Rapid guessing usually happens in high-stakes tests when there is
      insufficient time, and in low-stakes tests when there is lack of effort. These
      two qualitatively different test-taking behaviours, if ignored, will lead to
      violation of the local independence assumption and, as a result, yield biased
      item/person parameter estimation. We propose a mixture hierarchical model to
      account for differences among item responses and response time patterns arising
      from these two behaviours. The model is also able to identify the specific
      behaviour an examinee engages in when answering an item. A Monte Carlo
      expectation maximization algorithm is proposed for model calibration. A
      simulation study shows that the new model yields more accurate item and person
      parameter estimates than a non-mixture model when the data indeed come from two
      types of behaviour. The model also fits real, high-stakes test data better than a
      non-mixture model, and therefore the new model can better identify the underlying
      test-taking behaviour an examinee engages in on a certain item.

PMID- 25873486
TI  - Association between exposure to nonactionable physiologic monitor alarms and
      response time in a children's hospital.
AB  - BACKGROUND: Alarm fatigue is reported to be a major threat to patient safety, yet
      little empirical data support its existence in the hospital. OBJECTIVE: To
      determine if nurses exposed to high rates of nonactionable physiologic monitor
      alarms respond more slowly to subsequent alarms that could represent life
      threatening conditions. DESIGN: Observational study using video. SETTING:
      Freestanding children's hospital. PATIENTS: Pediatric intensive care unit (PICU)
      patients requiring inotropic support and/or mechanical ventilation, and medical
      ward patients. INTERVENTION: None. MEASUREMENTS: Actionable alarms were defined
      as correctly identifying physiologic status and warranting clinical intervention
      or consultation. We measured response time to alarms occurring while there were
      no clinicians in the patient's room. We evaluated the association between the
      number of nonactionable alarms the patient had in the preceding 120 minutes
      (categorized as 0-29, 30-79, or 80+ alarms) and response time to subsequent
      alarms in the same patient using a log-rank test that accounts for within-nurse
      clustering. RESULTS: We observed 36 nurses for 210 hours with 5070 alarms; 87.1%
      of PICU and 99.0% of ward clinical alarms were nonactionable. Kaplan-Meier plots
      showed incremental increases in response time as the number of nonactionable
      alarms in the preceding 120 minutes increased (log-rank test stratified by nurse
      P < 0.001 in PICU, P = 0.009 in the ward). CONCLUSIONS: Most alarms were
      nonactionable, and response time increased as nonactionable alarm exposure
      increased. Alarm fatigue could explain these findings. Future studies should
      evaluate the simultaneous influence of workload and other factors that can impact
      response time.

PMID- 25873488
TI  - Direct-S: a directed mass spectrometry method for biomarker verification in
      native serum.
AB  - Serum has been the logical choice and most-used bio-specimen for monitoring
      biomarkers. However, direct analysis of low-abundance biomarkers in serum is
      still a problem. Here, we have established a directed mass spectrometry
      (inclusion list driven MS) method, Direct-S, for direct quantification of protein
      biomarkers in native serum samples without high-abundance protein depletion or
      pre-fractionation. In Direct-S, an (18)O-labeling technique was used to produce
      internal standards of the targeted peptides, and only targeted peptides were
      selected for tandem mass spectrometry (MS/MS) fragmentation to increase
      sensitivity and efficiency. The (16)O/(18)O ion pairs of target peptides and the
      elution time/fragmental pattern of the internal standards were used to facilitate
      the identification of the low-abundance peptides. Using Direct-S, three candidate
      biomarkers, alpha1-antitrypsin (A1AT), galectin-3 binding protein (LG3BP) and
      cathepsin D (CTSD), which represent different abundance levels, were quantified
      in serum samples of colorectal cancer (CRC) patients and healthy candidates.
      Direct-S exhibited good linearity of response from 20 fmol to 0.5 nmol (r >
      0.9845). Reliable quantification across five orders of magnitude and as low as 71
      pg MUL(-1) was achieved in serum samples. In conclusion, Direct-S is a low cost,
      convenient and accurate method for verifying serum biomarkers. 

PMID- 25873489
TI  - Mate competition and evolutionary outcomes in genetically modified zebrafish
      (Danio rerio).
AB  - Demonstrating relationships between sexual selection mechanisms and trait
      evolution is central to testing evolutionary theory. Using zebrafish, we found
      that wild-type males possessed a significant advantage in mate competition over
      transgenic RFP Glofish(r) males. In mating trials, wild-type males were
      aggressively superior to transgenic males in male-male chases and male-female
      chases; as a result, wild-type males sired 2.5* as many young as did transgenic
      males. In contrast, an earlier study demonstrated that female zebrafish preferred
      transgenic males as mates when mate competition was excluded experimentally. We
      tested the evolutionary consequence of this conflict between sexual selection
      mechanisms in a long-term study. The predicted loss of the transgenic phenotype
      was confirmed. More than 18,500 adults collected from 18 populations across 15
      generations revealed that the frequency of the transgenic phenotype declined
      rapidly and was eliminated entirely in all but one population. Fitness component
      data for both sexes indicated that only male mating success differed between wild
      type and transgenic individuals. Our predictive demographic model based on
      fitness components closely matched the rate of transgenic phenotype loss observed
      in the long-term study, thereby supporting its utility for studies assessing
      evolutionary outcomes of escaped or released genetically modified animals.

PMID- 25873490
TI  - Academic laboratory medicine at 50 years and getting stronger.

PMID- 25873491
TI  - Decreasing inappropriate laboratory test utilization: controlling costs and
      improving quality of care.

PMID- 25873492
TI  - Searching for CALRity in myeloproliferative neoplasms.

PMID- 25873493
TI  - Positive surgical margins in renal cell carcinoma: translating tumor biology into
      clinical outcomes.

PMID- 25873494
TI  - Reducing duplicate testing: a comparison of two clinical decision support tools.
AB  - OBJECTIVES: Unnecessary duplicate laboratory testing is common and costly.
      Systems-based means to avert unnecessary testing should be investigated and
      employed. METHODS: We compared the effectiveness and cost savings associated with
      two clinical decision support tools to stop duplicate testing. The Hard Stop
      required telephone contact with the laboratory and justification to have the
      duplicate test performed, whereas the Smart Alert allowed the provider to bypass
      the alert at the point of order entry without justification. RESULTS: The Hard
      Stop alert was significantly more effective than the Smart Alert (92.3% vs 42.6%,
      respectively; P < .0001). The cost savings realized per alert activation was
      $16.08/alert for the Hard Stop alert vs $3.52/alert for the Smart Alert.
      CONCLUSIONS: Structural and process changes that require laboratory contact and
      justification for duplicate testing are more effective than interventions that
      allow providers to bypass alerts without justification at point of computerized
      physician order entry.

PMID- 25873495
TI  - Impact of a prospective review program for reference laboratory testing requests.
AB  - OBJECTIVES: To control the cost of reference laboratory testing, to ensure that
      its usage is medically appropriate, and to review the contribution of reference
      testing to patient care at our institution. METHODS: A multidisciplinary
      institutional committee was convened to manage the utilization of reference
      testing. A subset of tests was designated to be reviewed in real time by a team
      of clinical pathologists in consultation with clinical subject matter experts.
      RESULTS: Twelve percent of testing requests, accounting for approximately 18% of
      send-out costs, were determined to be clinically unnecessary or would not produce
      actionable results at that point during that patient's care and were therefore
      not performed. This intervention, combined with insourcing of frequently
      requested tests, resulted in a reduction in the costs of reference testing to
      less than half of that predicted by the rate of growth from 2005 to 2009.
      Molecular diagnostic tests displayed a higher cost per test than other forms of
      testing but had a similar degree of clinical impact. CONCLUSIONS: Formal
      prospective review of reference laboratory testing requests resulted in
      substantial cost containment and improved the efficiency of patient care.

PMID- 25873496
TI  - CALR, JAK2, and MPL mutation profiles in patients with four different subtypes of
      myeloproliferative neoplasms: primary myelofibrosis, essential thrombocythemia,
      polycythemia vera, and myeloproliferative neoplasm, unclassifiable.
AB  - OBJECTIVES: We investigated mutation profiles of CALR, JAK2, and MPL in 199
      Korean patients with myeloproliferative neoplasms (MPNs). METHODS: In total, 199
      patients with MPN (54 primary myelofibrosis [PMF], 79 essential thrombocythemia
      [ET], 58 polycythemia vera [PV], and eight MPN-unclassifiable [MPN-U]) and 4
      patients with acute panmyelosis with myelofibrosis (APMF) were retrospectively
      subjected to Sanger sequencing for CALR, JAK2, and MPL. RESULTS: The overall
      frequency of CALR mutations was 12.6% (type 1 mutation, 16 patients; type 2
      mutation, nine patients): most frequent in MPN-U (37.5%), followed by ET (17.7%)
      and PMF (14.8%). CALR mutations were not found in PV or APMF. CALR and JAK2 or
      MPL mutations were mutually exclusive. In PMF, the CALR mutations were associated
      with lower levels of leukocytes, lower bone marrow cellularity, and higher number
      of megakaryocytes. Patients with CALR-mutated ET more frequently progressed to
      the accelerated or blast phases compared with patients with JAK2 mutations. CALR
      mutations were frequently observed in the JAK2-negative MPNs, most frequently in
      MPN-U. CONCLUSIONS: The prognostic significance of CALR mutations likely differs
      among the MPN subtypes.

PMID- 25873497
TI  - Partial nephrectomy for renal tumors: lack of correlation between margin status
      and local recurrence.
AB  - OBJECTIVES: To evaluate the relationship between a positive resection margin in
      partial nephrectomy (PN) and local recurrence. METHODS: From January 2005 through
      December 2012, there were 473 PNs in 466 patients at the University of Chicago. A
      positive margin was defined as tumor extending to the inked specimen edge, either
      the parenchymal interface or the peripheral fibroadipose tissue. A local
      recurrence was defined as an ipsilateral tumor of identical histologic type.
      RESULTS: Renal cell carcinoma (RCC) accounted for 406 tumors: 243 clear cell RCCs
      (CRCCs), 77 papillary RCCs (PRCCs), and 47 chromophobe RCCs (CHRCCs). Sixty-one
      RCCs had positive margins: 43 CRCCs, six PRCCs, nine CHRCCs, and three
      miscellaneous cell types. Of the 61 positive margins, four CRCCs (all originally
      multifocal) had a local recurrence, two of which occurred in the same patient.
      One translocation RCC also recurred. Six cases with negative resection margins
      had a recurrence. CONCLUSIONS: A literature review of 3,803 cases, including our
      study, shows positive margins in 173, of which 13 recurred; however, 39 with
      negative margins also recurred. A positive margin in PN seldom correlates with a
      local recurrence. However, protection from recurrence is not ensured by a
      negative margin.

PMID- 25873498
TI  - Evaluation of multiple real-time PCR tests on nasal samples in a large MRSA
      surveillance program.
AB  - OBJECTIVES: We evaluated the LightCycler MRSA Advanced Test (Roche Molecular
      Diagnostics, Pleasanton, CA), the BD MAX MRSA assay (Becton Dickinson, Franklin
      Lakes, NJ), and the Xpert MRSA assay (Cepheid, Sunnyvale, CA) on nasal samples
      using the same population. METHODS: Admission and discharge nasal swabs were
      collected from inpatients using a double-headed swab. One swab was plated onto
      CHROMagar MRSA (CMA; Becton Dickinson, Sparks, MD) and then broken off into
      tryptic soy broth (TSB) for enrichment. TSB was incubated for 24 hours and then
      plated to CMA. The molecular tests were performed on the second swab. We analyzed
      the cost benefit of testing to evaluate what parameters affect hospital
      resources. RESULTS: A total of 27,647 specimens were enrolled. The
      sensitivity/specificity was 98.3%/98.9% for the LightCycler MRSA Advanced Test
      and 95.7%/98.8% for the Xpert MRSA assay, but the difference was not significant.
      The positive predictive value was 86.7% for the LightCycler MRSA Advanced Test,
      82.7% for the Xpert MRSA assay (P > .1), and 72.2% and for the BD MAX MRSA test
      (P < .001 compared with the LightCycler MRSA Advanced Test). All three assays
      were cost-effective, with the LightCycler MRSA Advanced Test having the highest
      economic return. CONCLUSIONS: Our results suggest that the performance of the
      three commercial assays is similar. When assessing economic cost benefit of
      methicillin-resistant Staphylococcus aureus screening, the two measures with the
      most impact are the cost of the test and the specificity of the assay results.

PMID- 25873499
TI  - Ewing sarcoma with extensive neural differentiation: a clinicopathologic,
      immunohistochemical, and molecular analysis of three cases.
AB  - OBJECTIVES: Three patients with Ewing sarcomas showing extensive neural
      differentiation are presented. METHODS: The patients were two women and one man
      between the ages of 15 and 35 years. Anatomically, one tumor was in the lung, one
      in the testis, and one in the cervix uteri. The symptoms were determined by the
      location of the neoplasm and included respiratory symptoms, testicular pain, and
      pelvic manifestations, respectively. Complete surgical resection of the tumors
      was performed. RESULTS: Histologically, all neoplasms showed similar
      characteristics-namely, a neoplastic cellular proliferation arranged in sheets
      and composed of small blue cells with round to oval nuclei and inconspicuous
      nucleoli typical for Ewing sarcoma. In addition, in two cases, there were areas
      characterized by the presence of neuropil, ganglion cells, and small cells most
      compatible with ganglioneuroblastoma, while in one tumor, the neural component
      was characterized by the presence of small cells with prominent perivascular
      pseudorosettes more closely resembling ependymoma. Immunohistochemical studies in
      all cases and molecular analysis in two tumors were in keeping with a diagnosis
      of Ewing sarcoma. CONCLUSIONS: The recognition of such histologic variants is
      important in the diagnostic assessment of these tumors to avoid
      misinterpretation, especially in small biopsy specimens.

PMID- 25873500
TI  - Significance of paneth cell metaplasia in Barrett esophagus: a morphologic and
      clinicopathologic study.
AB  - OBJECTIVES: The metaplastic intestinal epithelium in Barrett esophagus (BE)
      occasionally contains Paneth cells; however, little is known regarding the
      prevalence and significance of Paneth cell metaplasia (PCM) in BE. METHODS: We
      evaluated 757 esophageal biopsy specimens with intestinal metaplasia (IM) for
      PCM. Outcome analysis was performed in 299 cases with complete clinical data
      using multinomial logistic regression. RESULTS: Thirty-one percent (234/757) of
      the IM cases showed PCM. Paneth cells are decreased when BE epithelium becomes
      increasingly dysplastic. Long-segment BE shows significantly more PCM than short
      segment BE. On follow-up biopsies, patients without PCM (NPCM) are three times
      more likely to regress than patients with PCM, regardless of dysplasia, BE
      segment length, age, or sex. However, there is no significant difference in terms
      of progression to dysplasia/adenocarcinoma between the PCM and NPCM groups.
      CONCLUSIONS: The presence of PCM is associated with less disease regression and
      is not associated with more disease progression.

PMID- 25873502
TI  - Indirect estimation of pediatric between-individual biological variation data for
      22 common serum biochemistries.
AB  - OBJECTIVES: Derivation of between-individual biological variation (CVg) data
      requires repeat sampling of the same subject, which is undesirable and
      challenging in children. We describe an indirect sampling (data mining) approach
      to obtain these data in children. METHODS: Twenty-two serum biochemistry results
      from 6,989 children, who visited their primary care physician in Queensland,
      Australia, and were tested only twice within a year were included. The CVg and
      index of individuality of the boys and girls were estimated by year of age,
      according to the procedures recommended by Fraser and Harris. RESULTS: The CVg
      was generally higher during the first year of life and declined to reach a
      constant level by age 4 to 6 years, except for aspartate aminotransferase,
      alanine aminotransferase, gamma-glutamyltransferase, and phosphate. The CVg for
      these tended to increase after age 10 years. Most of the serum biochemistries
      examined in this study had indices of individuality 0.6 or less, except sodium,
      anion gap, bicarbonate, and chloride, which ranged from 0.6 to 1.4. The indices
      of individuality were very stable across all ages. CONCLUSIONS: These data are
      comparable to those reported by the Canadian Laboratory Initiative on Pediatric
      Reference Intervals study and the Ricos database for adults. This study reports
      the CVg trends and data for boys and girls by year of age, which have not been
      described previously.

PMID- 25873501
TI  - Extensive survey of STAT6 expression in a large series of mesenchymal tumors.
AB  - OBJECTIVES: Expression of strong nuclear STAT6 is thought to be a specific marker
      for solitary fibrous tumors (SFTs). Little is known about subtle expression
      patterns in other mesenchymal lesions. METHODS: We performed immunohistochemical
      studies against the C-terminus of STAT6 in tissue microarrays and whole sections,
      comprising 2366 mesenchymal lesions. RESULTS: Strong nuclear STAT6 was expressed
      in 285 of 2,021 tumors, including 206 of 240 SFTs, 49 of 408 well
      differentiated/dedifferentiated liposarcomas, eight of 65 unclassified sarcomas,
      and 14 of 184 desmoid tumors, among others. Expression in SFTs was predominately
      limited to the nucleus. Other positive tumors typically expressed both nuclear
      and cytoplasmic STAT6. Complete absence of STAT6 was most common in pleomorphic
      liposarcoma and alveolar soft part sarcoma (60% and 72% cases negative,
      respectively). CONCLUSIONS: Strong nuclear STAT6 is largely specific for SFTs.
      Physiologic low-level cytoplasmic/nuclear expression is common in mesenchymal
      neoplasia and is of uncertain significance.

PMID- 25873503
TI  - Detection and genotype of high-risk human papillomavirus in fine-needle aspirates
      of patients with metastatic squamous cell carcinoma is helpful in determining
      tumor origin.
AB  - OBJECTIVES: Recent studies have shown that human papillomavirus (HPV) is
      associated with a certain subset of head and neck squamous cell carcinoma (HNSCC)
      namely, those arising in the oropharynx. The objective of this study is to
      determine the efficacy, detection, and genotype of high-risk (HR) HPV using the
      Roche cobas 4800 system (Roche Molecular System, Pleasanton, CA). METHODS: Forty
      two fine-needle aspirate (FNA) specimens from 37 patients with cervical (n = 36)
      or mediastinal (n = 5) lymphadenopathy or a left parapharyngeal mass (n =1) were
      included in this prospective study. HR-HPV testing was performed on residual FNA
      material after direct smear preparation and, if positive, was further delineated
      into HPV 16/18 genotypes using the Roche cobas 4800 system. Follow-up included
      review of histologic material and/or electronic health records. RESULTS: Among
      those HNSCCs that were positive for HR-HPV, 18 (100%) of 18 originated from the
      oropharynx, whereas only two (13%) of 15 HR-HPV-negative HNSCCs originated from
      the oropharynx (chi(2) test, P < .05). p16 immunohistochemical assay and HPV 16
      in situ hybridization on corresponding histologic specimens were concordant with
      cytologic HR-HPV results. CONCLUSIONS: HR-HPV detection and genotyping can be
      performed on lymph node FNAs with metastatic squamous cell carcinoma using the
      Roche cobas 4800 system. The presence of HR-HPV and/or HPV 16 is a reliable
      indicator of the metastatic squamous cell carcinoma originating from the
      oropharynx.

PMID- 25873504
TI  - Pathologists' staging of multiple foci of lung cancer: poor concordance in
      absence of dramatic histologic or molecular differences.
AB  - OBJECTIVES: A long-standing problem in lung cancer pathology has been to
      determine whether two anatomically distinct foci of lung carcinoma are
      independent primaries or intrapulmonary metastases. While several proposals exist
      with respect to this problem, it is not known how pathologists use these
      proposals in actual practice. METHODS: We performed a voluntary survey of the
      Pulmonary Pathology Society, a self-selected group of pathologists with a
      specialty interest in pulmonary pathology, to determine their opinion on staging
      various specific scenarios of multiple foci of lung cancer. RESULTS: We found
      that there was a great deal of disagreement and uncertainty in the approach to
      these scenarios unless there were also unambiguous molecular markers or a
      dramatic difference in histology. CONCLUSIONS: Pathologists have a high degree of
      uncertainty and disagreement on staging multiple lung carcinomas. An improved
      pathologic method is required to distinguish separate primary tumors from
      intrapulmonary metastases. Until that is available, improved nomenclature is
      needed to convey the intrinsic uncertainty of the situation.

PMID- 25873505
TI  - Malignant effusions correlate with poorer prognosis in patients with diffuse
      large B-cell lymphoma.
AB  - OBJECTIVES: Serous effusions are a common manifestation of diffuse large B-cell
      lymphoma (DLBCL). However, their prognostic significance is controversial.
      METHODS: We searched for consecutive patients who had DLBCL with effusions from
      1999 through 2007. Primary effusion lymphoma was excluded. The presence of tumor
      cells in effusions (malignant effusions) was determined by cytology supplemented
      by flow cytometry, cell blocks with special studies, polymerase chain reaction
      for clonality, or conventional cytogenetics. RESULTS: Forty-one (18.4%) patients
      had effusions, with 24 (58.5%) developing at diagnosis and 17 (41.5%) during
      tumor course. Nineteen patients (46.0%) had malignant effusions, with six (31.6%)
      from local extension and 13 (68.4%) through wide dissemination. Interestingly,
      malignant effusion correlated with a high International Prognostic Index (IPI)
      score (r = 0.490, P = .002) and high tumor stage (r = 0.342, P = .031) and was a
      poor prognosticator (P < .001, log-rank test), even worse than stage IV disease
      (P = .036). In the multivariate analysis, malignant effusion (P = .056) and
      supportive care (P = .014) retained significance and were more powerful than IPI
      score and stage. CONCLUSIONS: Patients who have DLBCL with lymphomatous effusions
      have a poor prognosis and should be treated as having stage IV disease. The
      analysis of effusions for tumor cells would be a useful addition to the routine
      workup.

PMID- 25873506
TI  - B-ALL minimal residual disease flow cytometry: an application of a novel method
      for optimization of a single-tube model.
AB  - OBJECTIVES: Optimizing a clinical flow cytometry panel can be a subjective
      process dependent on experience. We develop a quantitative method to make this
      process more rigorous and apply it to B lymphoblastic leukemia/lymphoma (B-ALL)
      minimal residual disease (MRD) testing. METHODS: We retrospectively analyzed our
      existing three-tube, seven-color B-ALL MRD panel and used our novel method to
      develop an optimized one-tube, eight-color panel, which was tested prospectively.
      RESULTS: The optimized one-tube, eight-color panel resulted in greater efficiency
      of time and resources with no loss in diagnostic power. CONCLUSIONS: Constructing
      a flow cytometry panel using a rigorous, objective, quantitative method permits
      optimization and avoids problems of interdependence and redundancy in a large,
      multiantigen panel.

PMID- 25873507
TI  - Increased levels of tumor necrosis factor-alpha involved in rituximab-related
      acute pulmonary fibrosis in diffuse large B-cell lymphoma.
AB  - OBJECTIVES: Rituximab is a chimeric anti-CD20 monoclonal antibody with murine
      variable regions and human IgG1 constant regions that depletes B lymphocytes. It
      is used with increasing frequency in the treatment of patients with other
      hematologic malignancies and nonhematologic diseases for its safety and efficacy.
      Its major adverse effects are infusion related and most commonly consist of
      fever, chills, dyspnea, and hypotension. Rituximab-induced lung injury, such as
      interstitial pneumonitis and pulmonary fibrosis, is a rare complication but has
      been reported. METHODS: We herein report a patient with diffuse large B-cell non
      Hodgkin lymphoma who developed acute pulmonary fibrosis after treatment with
      rituximab. RESULTS: Simultaneous tumor necrosis factor (TNF)-alpha levels were
      significantly increased. The patient had a dramatic recovery that was confirmed
      by a repeated computed tomography scan, and the levels of TNF-alpha returned to
      normal after 2 weeks of methylprednisolone treatment. CONCLUSIONS: We observe
      that increased TNF-alpha levels may be involved in rituximab-related acute
      pulmonary fibrosis.

PMID- 25873508
TI  - Primary rhabdomyosarcoma of the pineal gland.
AB  - OBJECTIVES: To report a case of primary rhabdomyosarcoma (RMS) of the pineal
      gland in an adult, as well as review the literature on this rare entity. METHODS:
      The case is compared with previous reports of similar entities, with emphasis on
      this patient's characteristics and clinical presentation, investigations, and
      management. RESULTS: Diagnosis of primary RMS of the pineal gland was based on
      the presence of strap cells and multinucleated myotube-like structures, as well
      as tumor cell expression of skeletal muscle markers consistent with myogenic
      differentiation. Multimodality treatment was initiated based on pediatric
      protocols. Unfortunately, the disease progressed on treatment, and the patient
      survived only 5 months from diagnosis. CONCLUSIONS: Pineal RMS is a rare disease
      with poor prognosis. Optimal management is unknown but likely to involve
      aggressive multimodality therapy.

PMID- 25873509
TI  - Myocardial changes in a patient with anorexia nervosa: a case report and review
      of literature.
AB  - OBJECTIVES: Anorexia nervosa (AN) is an eating disorder with high mortality and
      morbidity. Much of the mortality is related to cardiovascular complications
      manifesting with electrocardiogram abnormalities and morphologic abnormalities
      documented on ultrasound. However, gross and histologic abnormalities in the
      heart have been rarely described in association with this eating disorder.
      METHODS: We present an autopsy case of an adult patient with AN. We describe the
      clinical presentation of this patient, as well as significant gross and
      histologic abnormalities of the heart, and discuss their implications. RESULTS:
      At autopsy, the heart was small with mainly a small left ventricle.
      Histologically, we found endocardial and interstitial fibrosis, areas of myxoid
      material deposition with mast cells in the background, and increased cytoplasmic
      lipofuscin. CONCLUSIONS: The gross findings in the heart correlate with the
      previously described anomalies on cardiac ultrasound of patients with AN. The
      fibrosis and myxoid material deposition might be a direct consequence of
      starvation and the mechanism of death in some patients with AN.

PMID- 25873510
TI  - Myeloid and lymphoid neoplasm with abnormalities of FGFR1 presenting with
      trilineage blasts and RUNX1 rearrangement: a case report and review of
      literature.
AB  - OBJECTIVES: Myeloid and lymphoid neoplasms with abnormalities of fibroblast
      growth factor receptor 1 gene (FGFR1) are a rare and aggressive disease group
      that harbors translocations of FGFR1 with at least 14 recognized partner genes.
      We report a case of a patient with a novel t(17;21)(p13;q22) with RUNX1
      rearrangement and trilineage blasts. METHODS: A 29-year-old man with relapsed T
      lymphoblastic lymphoma in the cervical nodes showed a myeloproliferative neoplasm
      in his bone marrow with three separate populations of immunophenotypically
      aberrant myeloid, T-lymphoid, and B-lymphoid blasts by flow cytometry.
      Cytogenetic and fluorescent in situ hybridization studies showed unique dual
      translocations of t(8;13)(p11.2;q12) and t(17;21)(p13;q22) with RUNX1
      rearrangement. RESULTS: The patient was initiated on a mitoxantrone, etoposide,
      and cytarabine chemotherapy regimen and died of complications of disease 1 month
      later. CONCLUSIONS: To our knowledge, this is the first reported case of a
      myeloid and lymphoid neoplasm with abnormalities of FGFR1 with t(17;21)(p13;q22)
      and trilineage blasts.

PMID- 25873511
TI  - Clinicocytopathologic correlation in an atypical presentation of lymphadenopathy
      with review of literature.
AB  - OBJECTIVES: To present a clinicocytopathologic correlation of an atypical case of
      cat scratch disease (CSD) involving retroperitoneal lymph nodes, with emphasis on
      communication between service teams for managing lymphadenopathy of unknown
      origin. We consider clinical and cytologic differential diagnoses and review the
      literature on atypical cases of CSD, with emphasis on abdominal presentation and
      cytologic findings. METHODS: Clinical services met with the cytology service to
      review clinical and pathologic features. Literature was reviewed via PubMed
      search (Harbor-UCLA subscriptions). Immunohistochemistry and Steiner silver
      stains were performed by Harbor-UCLA Department of Pathology. Enzyme-linked
      immunosorbent assay IgG and IgM Bartonella henselae titers were carried out by
      Quest Nichols Institute. RESULTS: Fine-needle aspirate Diff-Quik and Papanicolaou
      smears and H&E-stained cell block showed abundant histiocytes, monocytoid B
      cells, and numerous neutrophils associated with necrosis corresponding to a late
      stage of CSD infection. Silver stain was positive for clumps of pleomorphic
      organisms. IgM and IgG antibody titers were elevated. CONCLUSIONS: The cytologic
      findings of CSD in an atypical abdominal presentation are similar to those of a
      classic presentation. Laboratory workup for atypical CSD should include at least
      two other modalities aside from cytomorphologic features. Close clinical and
      cytologic correlation avoided potentially unnecessary and harmful surgery and
      enabled timely treatment.

PMID- 25873514
TI  - Correction.

PMID- 25873512
TI  - Paradoxical bleeding and thrombosis in a patient with afibrinogenemia and
      fibrinogen Mumbai mutation.
AB  - OBJECTIVES: Thrombosis is rarely reported in cases of afibrinogenemia and is
      generally associated with thrombophilia or replacement therapy. Often, it is
      difficult to predict whether the patients will bleed or whether they are exposed
      to the risk of thrombosis. METHODS: We report a patient with afibrinogenemia who
      presented with complete thrombosis of right hepatic, portal, and splenic veins
      and who described a lifelong history of bleeding. Direct sequencing of the three
      fibrinogen genes was performed to identify the mutation. RESULTS: DNA sequencing
      showed the presence of a homozygous for G8017A substitution in exon 8 of the
      fibrinogen beta-chain gene, resulting in a G434D missense mutation (Fibrinogen
      Mumbai). CONCLUSIONS: Presence of both bleeding and thrombotic manifestations in
      a patient with afibrinogenemia in the presence of other associated risk factors
      warrants a very careful individualized approach in the management of patients
      with afibrinogenemia.

PMID- 25873515
TI  - Effect of dietary excess of branched-chain amino acids on performance and serum
      concentrations of amino acids in growing pigs.
AB  - Depressed performance and availability of some amino acids (AA) in pigs fed
      excess Leu diets appear to be related to lower feed intake. Surplus Ile and Val
      may help to overcome this effect. An experiment was conducted with 24 pigs (31.8
      +/- 1.2 kg initial BW) to evaluate the effect of dietary excess of either Leu
      alone or with surplus Ile and Val on performance and serum concentration (SC) of
      essential AA. Treatments were as follows: T1, basal diet; T2, basal plus 0.43% L
      Leu (excess Leu); T3, basal added with 0.43% L-Leu, plus 0.20% L-Ile and 0.25% L
      Val (excess LIV). The basal diet was formulated to contain 0.90% standardized
      ileal digestible Lys and added with crystalline L-Lys, L-Thr, DL-Met, L-Trp, L
      Leu, L-Ile, L-His and L-Val to create essential AA:Lys ratios close to an ideal
      protein for growing pigs. All pigs were fed the same amount of feed twice a day
      (average, 3.42* the requirement of NEm). Blood samples were collected at 2.5
      (absorptive) and 11.0 h (post-absorptive) post-prandial to analyse SC of AA.
      Excess of either Leu or LIV did not affect growth rate nor feed conversion.
      Excess Leu increased Leu SC and decreased Ile and Val SC (p < 0.05) at both
      absorptive and post-absorptive phases, but excess LIV restored the SC of Ile and
      Val. The SC of other essential AA was not affected by excess of either Leu or
      LIV. The SC of all AA during absorptive, on average, was about two times higher
      than that of post-absorptive phase. These results suggest that the reduced
      availability (SC) of Ile and Val in pigs consuming excess Leu diets is attributed
      to a reduced absorption and increased cellular degradation rates of them.

PMID- 25873516
TI  - A note from history: Landmarks in history of cancer, part 7.
AB  - In the 2 and half decades reviewed (1970-1995), research established that
      chromosomal translocation, deletion, and DNA amplification are prerequisites to
      cancerogenesis and that oncogenes, tumor-suppressor genes, growth factors, and
      cytokines play crucial roles in the pathomechanism of cancer. Human
      papillomavirus, human immunodeficiency virus, herpes virus, and hepatitis B virus
      were identified as cancer-causing viruses. Several laboratory tests were
      developed for the detection of primary and recurrent cancers, and cancer
      prevention by screening methods was popularized. Sonography, computerized
      tomography, magnetic resonance imaging, positron emission tomography, excision of
      sentinel lymph nodes, and immunohistochemical techniques became routine
      procedures. Clinicopathologic staging and classification of tumors were
      standardized. Limited surgery, adjuvant and neoadjuvant chemoradiation, and the
      therapeutic use of monoclonal antibodies, tumor vaccines, and targeted
      chemotherapy became routine practice. The decline in cancer incidence and
      mortality demonstrated that cancer prevention and advancement in oncology are
      pivotal to success in the crusade against cancer. Above all, it was clearly
      established that the care of patients with cancer can be accomplished best in a
      multidisciplinary setting involving surgical oncologists, radiologists, radiation
      therapists, medical oncologists, surgical pathologists, and laboratory
      scientists. In conclusion, the 25 years from 1970 and 1995 are the high-water
      mark in clinical oncology, and this is the period when oncology turned from art
      to science.

PMID- 25873517
TI  - Free amino acids analysis by liquid chromatography with tandem mass spectrometry
      in several botanicals with antioxidant character.
AB  - A novel method based on liquid chromatography with tandem mass spectrometry for
      the analysis of 19 amino acids in plant materials is described. For the analysis,
      the plant material is extracted with 0.1 N hydrochloric acid with internal
      standards present in the extraction solution. The filtered extracts are injected
      using no clean-up into the liquid chromatographic system coupled with a triple
      quadrupole tandem mass spectrometer with an electrospray ionization source. The
      analytes are separated using ion pair chromatography on a reversed-phase column.
      The detection is performed in multiple-reaction monitoring positive-ion mode.
      Quantitation is obtained using calibrations. The validated procedure has been
      applied for the analysis of amino acids in 18 samples of plant material including
      botanicals with antioxidant character. The analysis requires 16 min separation
      time, has excellent precision and accuracy allowing amino acid analysis in a wide
      range of concentrations. 

PMID- 25873519
TI  - Refining reef-coral refugia.

PMID- 25873518
TI  - Intronic deletions of tva receptor gene decrease the susceptibility to infection
      by avian sarcoma and leukosis virus subgroup A.
AB  - The group of avian sarcoma and leukosis virus (ASLV) in chickens contains six
      highly related subgroups, A to E and J. Four genetic loci, tva, tvb, tvc and tvj,
      encode for corresponding receptors that determine the susceptibility to the ASLV
      subgroups. The prevalence of ASLV in hosts may have imposed strong selection
      pressure toward resistance to ASLV infection, and the resistant alleles in all
      four receptor genes have been identified. In this study, two new alleles of the
      tva receptor gene, tva(r5) and tva(r6), with similar intronic deletions were
      identified in Chinese commercial broilers. These natural mutations delete the
      deduced branch point signal within the first intron, disrupting mRNA splicing of
      the tva receptor gene and leading to the retention of intron 1 and introduction
      of premature TGA stop codons in both the longer and shorter tva isoforms. As a
      result, decreased susceptibility to subgroup A ASLV in vitro and in vivo was
      observed in the subsequent analysis. In addition, we identified two groups of
      heterozygous allele pairs which exhibited quantitative differences in host
      susceptibility to ASLV-A. This study demonstrated that defective splicing of the
      tva receptor gene can confer genetic resistance to ASLV subgroup A in the host. 

PMID- 25873520
TI  - Examples of Molecular Self-Assembly at Surfaces.
AB  - The self-assembly of molecules at surfaces can be caused by a range of physical
      mechanisms. Assembly can be driven by intermolecular forces, or molecule-surface
      forces, or both; it can result in structures that are in equilibrium or that are
      kinetically trapped. Here we review examples of self-assembly at surfaces
      focusing on a physical understanding of what causes patterns seen in experiment.
      Some apparently disparate systems can be described in similar physical terms,
      indicating that simple factors - such as the geometry and energy scale of
      intermolecular binding - are key to understanding the self-assembly of those
      systems. 

PMID- 25873521
TI  - Can hepatitis B virus DNA in semen be predicted by serum levels of hepatitis B
      virus DNA, HBeAg, and HBsAg in chronically infected men from infertile couples?
AB  - Hepatitis B virus (HBV) in semen is important for father-to-child transmission of
      HBV and has adverse effects on sperm quality. However, risk factors associated
      with HBV in semen remain unclear. Serum HBV DNA and hepatitis B e antigen (HBeAg)
      levels may pose a risk on HBV in semen. This study aims to examine whether serum
      HBV DNA, HBeAg, and hepatitis B surface antigen (HBsAg) level were associated
      with HBV DNA in semen. 151 male patients chronically infected with HBV from
      infertile couples were included. Serum HBsAg and HBeAg were determined using an
      electrochemiluminescence immune assay (ECLIA). Serum and seminal plasma HBV DNA
      were detected by the QIAGEN Real-Time HBV DNA assay. Of 151 patients, 143 (94.7%)
      were serum HBV DNA-positive and 65 (43.0%) were seminal plasma HBV DNA-positive.
      Serum HBV DNA and HBeAg level of seminal plasma HBV DNA-positive patients were
      significantly higher (p < 0.001) as compared with those of seminal plasma HBV DNA
      negative patients, HBsAg level of seminal plasma HBV DNA-positive patients was
      significantly lower (p < 0.001) compared with that of seminal plasma HBV DNA
      negative patients. The best serum HBV DNA, HBeAg, and HBsAg value for
      discriminating between seminal plasma HBV DNA-positive and HBV DNA-negative
      patients were >=6.9 log10 IU/mL (sensitivity 100.0%, specificity 90.7%), >14.8
      S/CO (sensitivity 96.9%, specificity 81.5%), and <1791.5 S/CO (sensitivity 81.5%,
      specificity 81.2%), respectively. The combination of serum HBV DNA and HBeAg had
      high diagnostic sensitivity (100.0%) and specificity (95.4%) for the presence of
      HBV DNA in semen. As such, these serum markers especially the combination of HBV
      DNA and HBeAg are useful predictors of the presence of HBV DNA in semen in HBV
      chronically infected men from infertile couples.

PMID- 25873522
TI  - Self-association of organic solutes in solution: a NEXAFS study of aqueous
      imidazole.
AB  - N K-edge near-edge X-ray absorption fine-structure (NEXAFS) spectra of imidazole
      in concentrated aqueous solutions have been acquired. The NEXAFS spectra of the
      solution species differ significantly from those of imidazole monomers in the gas
      phase and in the solid state of imidazole, demonstrating the strong sensitivity
      of NEXAFS to the local chemical and structural environment. In a concentration
      range from 0.5 to 8.2 mol L(-1) the NEXAFS spectrum of aqueous imidazole does not
      change strongly, confirming previous suggestions that imidazole self-associates
      are already present at concentrations more dilute than the range investigated
      here. We show that various types of electronic structure calculations (Gaussian,
      StoBe, CASTEP) provide a consistent and complete interpretation of all features
      in the gas phase and solid state spectra based on ground state electronic
      structure. This suggests that such computational modelling of experimental NEXAFS
      will permit an incisive analysis of the molecular interactions of organic solutes
      in solutions. It is confirmed that microhydrated clusters with a single imidazole
      molecule are poor models of imidazole in aqueous solution. Our analysis indicates
      that models including both a hydrogen-bonded network of hydrate molecules, and
      imidazole-imidazole interactions, are necessary to explain the electronic
      structure evident in the NEXAFS spectra. 

PMID- 25873523
TI  - High-order localized spoof surface plasmon resonances and experimental
      verifications.
AB  - We theoretically demonstrated and experimentally verified high-order radial spoof
      localized surface plasmon resonances supported by textured metal particles.
      Through an effective medium theory and exact numerical simulations, we show the
      emergence of these geometrically-originated electromagnetic modes at microwave
      frequencies. The occurrence of high-order radial spoof plasmon resonances is
      experimentally verified in ultrathin disks. Their spectral and near-field
      properties are characterized experimentally, showing an excellent agreement with
      theoretical predictions. Our findings shed light into the nature of spoof
      localized surface plasmons, and open the way to the design of broadband plasmonic
      devices able to operate at very different frequency regimes. 

PMID- 25873524
TI  - Synthesis of fluorescent and low cytotoxicity phenol formaldehyde resin (PFR)@Ag
      composites for cell imaging and antibacterial activity.
AB  - Ag nanoparticles (NPs) were loaded onto the surface of phenol formaldehyde resin
      (PFR) NPs without any reducing agent. The as-synthesized PFR@Ag composites have
      low cytotoxicity, which makes them promising antibacterial agents. Furthermore,
      the good fluorescence of PFR could be used for cell imaging.

PMID- 25873525
TI  - Assessing the utility of a telephonically delivered psychoeducational
      intervention to improve health-related quality of life in African American breast
      cancer survivors: a pilot trial.

PMID- 25873526
TI  - Palladium(0)/PAr3 -Catalyzed Intermolecular Amination of C(sp(3) )?H Bonds:
      Synthesis of beta-Amino Acids.
AB  - An intermolecular C(sp(3))-H amination using a Pd(0) /PAr3 catalyst was
      developed. The reaction begins with oxidative addition of R2 N-OBz to a Pd(0)
      /PAr3 catalyst and subsequent cleavage of a C(sp(3))-H bond by the generated Pd
      NR2 intermediate. The catalytic cycle proceeds without the need for external
      oxidants in a similar manner to the extensively studied palladium(0)-catalyzed C
      H arylation reactions. The electron-deficient triarylphosphine ligand is crucial
      for this C(sp(3))-H amination reaction to occur.

PMID- 25873527
TI  - General theory of frictional heating with application to rubber friction.
AB  - The energy dissipation in the contact regions between solids in sliding contact
      can result in high local temperatures which may strongly effect friction and
      wear. This is the case for rubber sliding on road surfaces at speeds above 1 mm
      s(-1). We derive equations which describe the frictional heating for solids with
      arbitrary thermal properties. The theory is applied to rubber friction on road
      surfaces and we take into account that the frictional energy is partly produced
      inside the rubber due to the internal friction of rubber and in a thin
      (nanometer) interfacial layer at the rubber-road contact region. The heat
      transfer between the rubber and the road surface is described by a heat transfer
      coefficient which depends on the sliding speed. Numerical results are presented
      and compared to experimental data. We find that frictional heating results in a
      kinetic friction force which depends on the orientation of the sliding block,
      thus violating one of the two basic Leonardo da Vinci 'laws' of friction. 

PMID- 25873529
TI  - Clinical trial to evaluate the performance of a flexible self-adherent absorbent
      dressing coated with a soft silicone layer compared to a standard wound dressing
      after orthopedic or spinal surgery: study protocol for a randomized controlled
      trial.
AB  - BACKGROUND: Postoperative wound infection is a preventable risk. One potential
      postoperative complication is blistering, which leads to increased pain, delayed
      healing, and higher care costs. The incidence of wound blisters has been reported
      to be between 6 and 24%. The aim of this study is to assess whether the risks of
      postoperative blistering and wound infections within the first 6 days postsurgery
      will be reduced using a special dressing compared to a standard one.
      METHODS/DESIGN: This is a randomized clinical trial in a University hospital.
      Patients presenting for knee or hip arthroplasty or spine procedures will be
      assessed against study inclusion and exclusion criteria. After giving written
      informed consent, patients will be randomized to participate in the 7-day study
      during hospitalization. One hundred patients will be randomized per group. The
      primary outcome measure is blistering incidence from day 0 to day 6 postsurgery.
      Photo documentation will be evaluated in a blinded manner by the Clinical
      Evaluation Committee (CEC). DISCUSSION: A new dressing will be compared to the
      standard wound dressing regarding the risk of postoperative blistering, wound
      infection, and patient comfort. This study will assess the potential advantages
      of a modern wound dressing. TRIAL REGISTRATION: ClinicalTrials.gov identifier
      NCT01988818 (Entered 13 November 2011).

PMID- 25873531
TI  - Positive empathy: a therapeutic skill inspired by positive psychology.
AB  - OBJECTIVE: Positive empathy (PE), a type of empathy response that focuses on a
      client's hidden message of desire for a better life, was hypothesized to increase
      the expression of positive emotions, approach goals, and strengths, and to
      communicate equivalent understanding when compared to traditional empathy (TE).
      METHOD: We examined 4 hypotheses in 2 studies. In study 1, college participants
      read therapy session vignettes incorporating PE or TE and then listed the
      client's strengths and goals and rated the therapist and how well they imagined
      themselves as the client in the vignettes. In study 2, therapist-client dyads
      attended 6 weekly sessions that incorporated both PE and TE, after which clients
      rated therapists' level of empathic understanding and session observers rated
      clients' emotional responses, revelations of strengths, and goals in response to
      empathy. RESULTS: In both studies, the results of PE and TE were similar, while
      PE elicited a greater number of approach goals. In study 2, clients expressed
      more strengths and positive emotions after PE responses than TE. CONCLUSION: Our
      results support PE for enhancing client growth (i.e., when a client pursues
      approach goals, enlists strengths, and experiences positive emotions), which is
      consistent with the process of positive psychology-informed psychotherapy.

PMID- 25873532
TI  - Using metformin in the presence of renal disease.

PMID- 25873528
TI  - The roles of chromatin-remodelers and epigenetic modifiers in kidney cancer.
AB  - Clear cell renal cell carcinoma (ccRCC) is the major subtype of kidney cancer
      that is characterized by frequent inactivation of the von Hippel-Lindau (VHL)
      gene in 80-90% of the tumors. Recent reports using massive parallel sequencing
      technologies have discovered additional cancer driver genes. PBRM1 was found to
      be mutated in about 40% of ccRCC tumors, whereas BAP1 and SETD2 were each mutated
      in about 10-15% of ccRCC tumors. JARID1C and UTX, two histone H3 demethylases,
      were also found to harbor mutations in ccRCC, albeit at lower rates. ccRCC tumors
      display a high degree of intra-tumoral heterogeneity, with some mutations present
      in all cancer cells (ubiquitous), whereas others are subclonal. The VHL mutations
      were always ubiquitous in the tumors; PBRM1 mutations were also ubiquitous but to
      a lesser extent. On the contrary, mutations in BAP1, SETD2, JARID1C, and UTX were
      all subclonal, meaning that they were present in a subset of cancer cells in a
      tumor. The prognostic value of PBRM1 mutations in ccRCC is still controversial,
      whereas BAP1 mutations were tightly linked to worse clinical outcomes in multiple
      studies. The molecular functions of these newly identified cancer driver genes
      are discussed, and they were known readers, writers, or erasers of histone marks
      on histone H2 and H3 tails that are very close to each other, suggesting that
      these factors might functionally interact and affect common pathways. The studies
      on these newly identified tumor suppressors will shed light on ccRCC
      tumorigenesis and development, and will likely lead to development of novel
      therapeutic interventions for ccRCC patients. 

PMID- 25873530
TI  - Effects of weight management program on postural stability and neuromuscular
      function among obese children: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Childhood obesity is one of the most critical public health problems
      in the world. It is associated with low neuromuscular function and postural
      deformities. Whether weight loss can improve postural stability and neuromuscular
      control, benefit daily activities, or prevent injury is unknown. Therefore, this
      study attempts to investigate the effect of a 6 month weight management program
      on postural stability and neuromuscular control among obese children.
      METHODS/DESIGN: We will conduct a prospective, single-blind, randomized
      controlled trial with 120 prepubescent obese children. Participants will be
      randomly assigned to a weight management group or a control group. The weight
      management group will participate in a dietary and exercise program. The control
      group will receive health education. After the intervention, participants will be
      followed for 6 months with no active intervention. The primary and secondary
      outcomes will be assessed at the baseline, and after 6 months and 12 months.
      Primary outcome measures will include body weight, body height, body mass index,
      waist circumference, hip circumference, and body fat percentage. Secondary
      outcome measures will include three-dimensional functional biomechanics in
      different tasks, proprioception tests of the knee and ankle, neuromuscular
      response of the leg muscles, and muscle strength tests of the knee and ankle.
      Furthermore, adverse events will be recorded and analyzed. An intention-to-treat
      analysis will be performed if any participants withdraw from the trial.
      DISCUSSION: The important features of this trial include the randomization
      procedures and large sample size. This study attempts to estimate the effect of
      weight loss intervention on outcomes, including daily life function, postural
      stability, and neuromuscular control in prepubescent obese children. Therefore,
      our results can be useful for obese children, medical staff, and healthcare
      decision makers. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-IOB
      15005874.

PMID- 25873533
TI  - CRH knockout inhibits the murine innate immune responses in association with
      endoplasmic reticulum stress after thermal injury.
AB  - BACKGROUND: Previous studies in our laboratory have demonstrated the hypothalamus
      destruction and adrenalectomy could blunt the innate immunity while boosting the
      excessive inflammation after injury. We aimed to investigate the effects of
      corticotrophin-releasing hormone knockout (CRH KO) on the innate immune responses
      in macrophages as well as to elucidate the underlying mechanism. METHODS: The
      chemotaxis and phagocytosis activities of macrophages, bacteria translocation,
      plasma tumor necrosis factor (TNF)-alpha secretion, and intestinal injury were
      observed in the presence of the endoplasmic reticulum stress after thermal injury
      in CRH KO mice. Meanwhile, the messenger RNA (mRNA) and protein expression of
      glucose response protein 78 (GRP78), X-box binding protein 1 (XBP1), and
      activating transcription factor 6 (ATF6) in macrophages was also determined.
      RESULTS: After thermal injury, the chemotaxis and phagocytosis of peritoneal
      macrophages were increased, which were both reversed by CRH gene deficiency. The
      gut-derived bacteria translocation to liver tissues, lung tissues and mesenteric
      lymph nodes was significantly strengthened in CRH KO mice compared with CRH wild
      type littermates. Circulating TNF-alpha level was increased markedly in response
      to thermal injury and CRH KO further increased its secretion. Furthermore, the
      mRNA and protein levels of GRP78, XBP1, and ATF6 in peritoneal macrophages
      increased, while their expressions in CRH KO mice all decreased significantly.
      CRH KO mice showed enhancement of inflammatory responses and severe tissue
      injuries after thermal injury. CONCLUSION: CRH exerted immune defensive actions
      on immune cells and organs in the early phase of injury, suggesting that the
      underlying mechanisms are related to endoplasmic reticulum stress.

PMID- 25873534
TI  - Impact of variant pancreatic arterial anatomy and overlap in regional perfusion
      on the interpretation of selective arterial calcium stimulation with hepatic
      venous sampling for preoperative localization of occult insulinoma.
AB  - BACKGROUND: To determine the impact of variant pancreatic arterial anatomy and
      overlap in regional perfusion on the interpretation of selective arterial calcium
      stimulation (SACST) with hepatic venous sampling for preoperative localization of
      occult insulinoma. METHODS: An institutional review board-approved retrospective
      review was undertaken of 42 patients with surgically confirmed, occult insulinoma
      who underwent SACST from January 1996 to March 2014. Location of the insulinoma
      was predicted initially based on the biochemical results of SACST alone according
      to Doppman's criteria. Pancreatic arteriograms were reviewed blinded to the
      biochemical results and the regional perfusion of each artery assessed. The
      anatomic and perfusion data were combined with the biochemical results to make a
      second prediction and compared with the surgical findings. RESULTS: The
      biochemical results were positive in 1, 2, and 3 arterial distributions in 73.8%,
      21.4%, and 4.8% of patients, respectively. The celiac trunk and superior
      mesenteric artery (SMA) anatomy were aberrant in 38.1% and 35.7% of patients,
      respectively. Clinically significant variations included dorsal pancreatic artery
      replaced to SMA (21.4%) and celiac stenosis (4.8%). Significant variation and
      overlap in regional pancreatic perfusion was observed, particularly for the SMA.
      Sensitivity for insulinoma localization was 54.8% (diagnostic arteriography),
      73.8% (biochemical data), 88.1% (biochemical, anatomic, perfusion data), and
      92.8% (arteriographic, biochemical, anatomic, perfusion data). CONCLUSION:
      Careful review of the pancreatic arterial anatomy and regional perfusion is
      critical for correct interpretation of the biochemical results of SACST and
      improves the sensitivity of localization for occult insulinoma, particularly in
      the presence of pancreatic arterial variants or overlap in regional perfusion.

PMID- 25873535
TI  - Induction of immunogenic cell death by chemotherapeutic platinum complexes.
AB  - There is compelling evidence suggesting that the immune-modulating effects of
      many conventional chemotherapeutics, including platinum-based agents, play a
      crucial role in achieving clinical response. One way in which chemotherapeutics
      can engage a tumor-specific immune response is by triggering an immunogenic mode
      of tumor cell death (ICD), which then acts as an "anticancer vaccine". In spite
      of being a mainstay of chemotherapy, there has not been a systematic attempt to
      screen both existing and upcoming Pt agents for their ICD ability. A library of
      chemotherapeutically active Pt agents was evaluated in an in vitro phagocytosis
      assay, and no correlation between cytotoxicity and phagocytosis was observed. A
      Pt(II) N-heterocyclic carbene complex was found to display the characteristic
      hallmarks of a type II ICD inducer, namely focused oxidative endoplasmic
      reticulum (ER) stress, calreticulin exposure, and both HMGB1 and ATP release, and
      thus identified as the first small-molecule immuno-chemotherapeutic agent.

PMID- 25873536
TI  - Collaborative care interventions: a solution to the treatment of depression in
      the oncology setting.

PMID- 25873537
TI  - Reduced cortical folding is a heritable feature of non-affective psychosis.

PMID- 25873538
TI  - Beyond the impact factor?

PMID- 25873539
TI  - Statistics for clinicians: An introduction to logistic regression.

PMID- 25873540
TI  - Biological redox cycling of iron in nontronite and its potential application in
      nitrate removal.
AB  - Biological redox cycling of structural Fe in phyllosilicates is an important but
      poorly understood process. The objective of this research was to study
      microbially mediated redox cycles of Fe in nontronite (NAu-2). During the
      reduction phase, structural Fe(III) in NAu-2 served as electron acceptor, lactate
      as electron donor, AQDS as electron shuttle, and dissimilatory Fe(III)-reducing
      bacterium Shewanella putrefaciens CN32 as mediator in bicarbonate- and PIPES
      buffered media. During the oxidation phase, biogenic Fe(II) served as electron
      donor and nitrate as electron acceptor. Nitrate-dependent Fe(II)-oxidizing
      bacterium Pseudogulbenkiania sp. strain 2002 was added as mediator in the same
      media. For all three cycles, structural Fe in NAu-2 was able to reversibly
      undergo three redox cycles without significant dissolution. Fe(II) in bioreduced
      samples occurred in two distinct environments, at edges and in the interior of
      the NAu-2 structure. Nitrate reduction to nitrogen gas was coupled with oxidation
      of edge-Fe(II) and part of interior-Fe(II) under both buffer conditions, and its
      extent and rate did not change with Fe redox cycles. These results suggest that
      biological redox cycling of structural Fe in phyllosilicates is a reversible
      process and has important implications for biogeochemical cycles of carbon,
      nitrogen, and other nutrients in natural environments. 

PMID- 25873541
TI  - Time-Dependent Pressure and Flow Behavior of a Self-oscillating Laryngeal Model
      With Ventricular Folds.
AB  - OBJECTIVE: The purpose of the study was to better understand the pressure-flow
      behavior of a self-oscillating vocal fold model at various stages of the glottal
      cycle. METHODS: An established self-oscillating vocal fold model was extended to
      include the false vocal folds (FVFs) and was used to study time-dependent
      pressure and velocity distributions through the larynx (including the true vocal
      folds [TVFs] and FVFs). Vocal fold vibration was modeled with a finite element
      method, laryngeal flow was simulated with the solution of unsteady Navier-Stokes
      equations, and the acoustics of the vocal tract was modeled with a wave
      reflection method. RESULTS: The results demonstrate realistic phonatory behaviors
      and therefore may be considered as a pedagogical tool for showing detailed
      aerodynamic, kinematic, and acoustic characteristics. The TVFs self-oscillated
      regularly with reasonable amplitude and mucosal waves. There were large pressure
      gradients in the glottal region. The centerline velocity was highest during
      glottal closing and sharply dropped near the center of the flow vortex. The
      average centerline velocity was about 25 m/second in the glottal region. The
      transglottal pressure was higher during glottal closing when the glottal shape
      was divergent and pressure recovery was present within the glottis. The
      centerline velocity increased as expected throughout the convergent glottis,
      tended to decrease throughout the divergent glottis, and decreased past the TVFs
      within the ventricle-FVF region. CONCLUSIONS: This model produces realistic
      results and demonstrates interactions among phonation variables of a highly
      instructive nature, including the influence of the FVFs.

PMID- 25873542
TI  - Does Cervical Muscular Contraction Affect the Measurement for
      Electroglottographic Perturbation Parameters?
AB  - OBJECTIVES: The purpose was to assess whether cervical muscular contraction
      during phonation influences the period and amplitude perturbation quotients (PPQ
      and APQ, respectively) of electroglottographic (EGG) signals, and whether high
      pass filtering can attenuate these effects. STUDY DESIGN: Prospective. METHODS:
      We included 19 nondysphonic speakers and 21 patients with muscle tension
      dysphonia. During the recording of acoustic and EGG signals, each participant was
      instructed to naturally phonate sustained vowels /i:/ and /a:/ (NP tasks), and
      additionally, each nondysphonic participant was asked to phonate the same vowels
      in a nondysphonic voice quality while contracting the cervical muscles (muscular
      contracted phonation [MCP] tasks). To confirm the contraction, surface and needle
      electromyography (EMG) was performed. The EGG signals were high-pass filtered at
      different cutoff frequencies from 0 to 90 Hz and were subsequently analyzed for
      the PPQ and APQ. RESULTS: Compared with the NP tasks, the MCP tasks enhanced the
      cervical EMG activities ranging from 0 to more than 1000 Hz, but conferred only
      low-frequency noise to the EGG signals under 50 Hz and increased the values for
      EGG-APQ, but not EGG-PPQ. These EGG-APQ values exhibited gradual decreases after
      high-pass filtering with an increase in the cutoff frequency ranging from 0 to 50
      Hz in both groups, followed by plateaus during the MCP tasks in the nondysphonic
      group. CONCLUSIONS: The present results demonstrate that cervical muscular
      contraction seriously affects the EGG-APQ values for unfiltered EGG signals
      independent of the EMG activities and that appropriate high-pass filtering over
      50 Hz can attenuate these effects.

PMID- 25873543
TI  - Describing Speech Usage in Daily Activities in Typical Adults.
AB  - OBJECTIVES: "Speech usage" refers to what people want or need to do with their
      speech to meet communication demands in life roles. The purpose of this study was
      to contribute to validation of the Levels of Speech Usage scale by providing
      descriptive data from a sample of adults without communication disorders,
      comparing this scale to a published Occupational Voice Demands scale and
      examining predictors of speech usage levels. STUDY DESIGN: This is a survey
      design. METHODS: Adults aged >=25 years without reported communication disorders
      were recruited nationally to complete an online questionnaire. The questionnaire
      included the Levels of Speech Usage scale, questions about relevant occupational
      and nonoccupational activities (eg, socializing, hobbies, childcare, and so
      forth), and demographic information. Participants were also categorized according
      to Koufman and Isaacson occupational voice demands scale. RESULTS: A total of 276
      participants completed the questionnaires. People who worked for pay tended to
      report higher levels of speech usage than those who do not work for pay.
      Regression analyses showed employment to be the major contributor to speech
      usage; however, considerable variance left unaccounted for suggests that
      determinants of speech usage and the relationship between speech usage,
      employment, and other life activities are not yet fully defined. CONCLUSIONS: The
      Levels of Speech Usage may be a viable instrument to systematically rate speech
      usage because it captures both occupational and nonoccupational speech demands.
      These data from a sample of typical adults may provide a reference to help in
      interpreting the impact of communication disorders on speech usage patterns.

PMID- 25873544
TI  - Performing Lieder: Expert Perspectives and Comparison of Vibrato and Singer's
      Formant With Opera Singers.
AB  - This article reports three studies about performance of lieder, and in particular
      in comparison with opera performance. In study 1, 21 participants with experience
      in music performance and teaching completed a survey concerning various
      characteristics of lieder performance. The results showed that there was
      consensus between the literature and the assessment of an expert panel-that a
      "natural" and "unoperatic" vibrato was favored, and that diction, text, and
      variation of tone are all important aspects of lieder performance. Two acoustic
      analyses were conducted to investigate genre-specific differences of the singer's
      formant and vibrato parameters. The first analysis (study 2) used 18 single quasi
      unaccompanied notes from commercial recordings of two lieder, and, for
      comparison, 20 single unaccompanied notes from an opera. Vibrato rate was
      statistically identical between the two genres at ~6.4 Hz; however, lieder
      featured a longer delay in vibrato onset. Vibrato extent was smaller for lieder
      (~112 cents) compared with opera (~138 cents). The singer's formant, which is
      generally associated with opera, was at times observed in the lieder recordings;
      however, this was at an overall significantly weaker intensity than in the opera
      recordings. The results were replicated in study 3, where recordings using only
      singers who performed in both lied and opera were analyzed. This direct
      comparison used 45 lieder notes and 55 opera notes and also investigated three
      different methods of analyzing the singer's formant. A number of consistencies
      and inconsistencies were identified between acoustic parameters reported in
      studies 2 and 3, and the beliefs of singing teachers and scholars in the
      literature and study 1.

PMID- 25873545
TI  - An Acoustic and Electroglottographic Study of the Aging Voice With and Without an
      Open Jaw Posture.
AB  - OBJECTIVES: This study aimed to determine if the use of an "open jaw" posture in
      healthy aging adults would result in voice improvement detectable through
      acoustic and electroglottographic measurements. STUDY DESIGN: A convenience
      sampling strategy was used to recruit 85 participants, with at least five females
      and five males in each of four age groups, between age 35 and 50 years (35+),
      above 50 (50+), 60+, and 70+ years. METHODS: Participants sustained the vowel /a/
      at three pitch levels (normal, low, and high) and repeated the test sentence "We
      saw two cars" in both a normal and an open jaw postures. A selection of acoustic
      and electroglottographic measures were derived from the steady midportion of the
      vowel segments extracted from the sustained and embedded vowels to identify
      measures sensitive to the effects of jaw posture, age group, gender, and pitch.
      RESULTS: Results from a four-way (two jaw postures * four age groups * two
      genders * three pitch levels) Mixed Model Multivariate Analysis of Variance
      showed a significant four-way interaction effect. For both genders, an open jaw
      posture led to an increase of fundamental frequency (F0), formant one frequency,
      and vowel space area and a decrease of the amplitude difference of the first two
      harmonics and %Jitter. With an open jaw posture, speed quotient decreased for
      females and open quotient increased for females but decreased for males.
      CONCLUSIONS: An open jaw posture was generally associated with positive changes
      in vocal behaviors, including higher F0, improved phonatory stability, and voice
      clarity.

PMID- 25873546
TI  - The Flow and Pressure Relationships in Different Tubes Commonly Used for Semi
      occluded Vocal Tract Exercises.
AB  - This experimental study investigated the back pressure (P(back)) versus flow (U)
      relationship for 10 different tubes commonly used for semi-occluded vocal tract
      exercises, that is, eight straws of different lengths and diameters, a resonance
      tube, and a silicone tube similar to a Lax Vox tube. All tubes were assessed with
      the free end in air. The resonance tube and silicone tube were further assessed
      with the free end under water at the depths from 1 to 7 cm in steps of 1 cm. The
      results showed that relative changes in the diameter of straws affect P(back)
      considerably more compared with the same amount of relative change in length.
      Additionally, once tubes are submerged into water, P(back) needs to overcome the
      pressure generated by the water depth before flow can start. Under this
      condition, only a small increase in P(back) was observed as the flow was
      increased. Therefore, the wider tubes submerged into water produced an almost
      constant P(back) determined by the water depth, whereas the thinner straws in air
      produced relatively large changes to P(back) as flow was changed. These
      differences may be taken advantage of when customizing exercises for different
      users and diagnoses and optimizing the therapy outcome.

PMID- 25873547
TI  - Diagnostic Delays in Spasmodic Dysphonia: A Call for Clinician Education.
AB  - PURPOSE: Spasmodic dysphonia (SD) is a rare but often debilitating disease. Due
      to lack of awareness among practitioners and lack of well-defined diagnostic
      criteria, it can be difficult for patients with SD to receive a diagnosis and
      subsequent treatment. There is currently no literature documenting the efficacy
      of the medical community in recognizing and diagnosing this disorder. We aimed to
      quantify the patients' experiences with obtaining a diagnosis of SD. METHODS: One
      hundred seven consecutive patients with SD completed questionnaires about their
      experiences with SD. Patients were recruited either during outpatient laryngology
      visits or during participation in a National Institutes of Health funded study
      investigating SD. RESULTS: It took patients an average of 4.43 years (53.21
      months) to be diagnosed with SD after first going to a physician with vocal
      symptoms. Patients had to see an average of 3.95 physicians to receive a
      diagnosis of SD. Patients (31.4%) had been prescribed medications other than
      botulinum toxin to treat their symptoms. Patients (30%) attempted alternative
      therapies for treatment of SD, such as chiropractor or dietary modification.
      CONCLUSIONS: Despite advances in diagnostic modalities in medicine, the diagnosis
      of SD still remains elusive. Objective criteria for the diagnosis of SD and
      increased clinician education are warranted to address this diagnostic delay.

PMID- 25873548
TI  - Children's Subjective Ratings and Opinions of Typical and Dysphonic Voice After
      Performing a Language Comprehension Task in Background Noise.
AB  - OBJECTIVE: Previous studies suggest that dysphonic voices are perceived more
      negatively than typical voices, and it is possible that vocal perception
      influences academic achievement and comprehension. This study assessed children's
      subjective ratings and opinions of a typical and dysphonic voice after performing
      a language comprehension task in background noise. It also explored if subjective
      ratings were related to performance in the comprehension task. STUDY DESIGN:
      Ninety-three 8-year-old children participated and were randomly allocated to two
      groups. METHODS: A digital version of the Test for Reception of Grammar, version
      2 (TROG-2) was used. In TROG-2, the child listens to a sentence and then, out of
      four possible pictures, selects the picture that corresponds to the sentence
      content. Each sentence assesses a specific grammatical construction. Test
      instructions were recorded using one speaker with two different voice qualities
      (typical voice and provoked dysphonic voice). One group of children performed
      TROG-2 with the typical voice and the other with the dysphonic voice, both
      presented in a multitalker babble noise using earphones. All children rated their
      subjective perception of the voice. RESULTS: The dysphonic voice received poorer
      ratings than the typical voice. Children making more positive ratings of the
      voice performed better on earlier blocks in TROG-2, but only in the typical voice
      group. CONCLUSIONS: Children perceived the dysphonic voice more negatively even
      when listening to the same speaker. Performance is related to the perception of
      the voice, but only when the perceptual load of the task-relevant stimuli is
      sufficiently low.

PMID- 25873549
TI  - Atypical Presentation of a Common Disease: Shingles of the Larynx.
AB  - OBJECTIVE: Herpes zoster is a neurocutaneous disease resulting from the
      reactivation of endogenous varicella-zoster virus (VZV) in dorsal sensory or
      cranial nerve ganglia. Rarely, this infection manifests without the
      characteristic dermatomal rash, a condition termed zoster sine herpete. Viral
      spreading of herpes zoster in the head and neck may manifest as various signs and
      symptoms because of the multiple possible combinations of cranial neuropathies.
      With only six cases reported in the English literature up to now, isolated
      neuropathies of the vagus nerve in the absence of cutaneous lesions tend to be
      misdiagnosed as idiopathic laryngeal paralysis. METHODS: We report a case of
      herpes zoster of the larynx in an 80-year-old man presenting with sore throat,
      dysphagia, and hoarseness. RESULTS: Endoscopic examination revealed unilateral
      vocal fold paralysis, pooling of secretions, and mucosal vesicles of the
      hemilarynx. After the diagnosis of VZV infection with polymerase chain reaction
      (PCR) testing, the patient was treated with valacyclovir and corticosteroids,
      leading to complete recovery after 2 months. CONCLUSIONS: Herpes zoster of the
      larynx is an uncommon condition that should be included in the differential
      diagnosis of laryngeal paralysis of idiopathic cause. We recommend performing a
      thorough examination of the pharyngolaryngeal structures and ordering PCR testing
      as the diagnostic method of choice.

PMID- 25873550
TI  - Esophageal anastomotic leak does not affect ability to receive adjuvant
      treatment.
AB  - BACKGROUND: Esophageal anastomotic leak is associated with high morbidity and
      mortality and potentially lethal if not recognized promptly and treated
      aggressively. While many studies have attempted to delineate the surgical
      techniques associated with lower rates of anastomotic leak, few have attempted to
      determine its long term effects on adjuvant therapy and patient quality of life.
      METHODS: We reviewed our prospective 350 patient esophageal-gastric database and
      found 194 esophageal anastomoses performed from 1994 to 2013. Leaks were
      classified based on timing, severity, and location. We then compared their
      postoperative courses of adjuvant treatment, morbidity/mortality, and quality of
      life measured by Karnofsky performance status and EORTC score. Statistical
      correlations were calculated with chi(2) , T-test, Kaplain-Meier, ANOVA, and Cox
      Regression analyses as appropriate. RESULTS: Of 194 patients receiving esophageal
      anastomoses for cancer, 35 (18%) developed clinically diagnosed anastomotic leak
      27 from esophagogastric and 8 from esophagojejunal. These groups were similar in
      preoperative history, preoperative staging, and type of tumor. Type of operation
      and variations in operative technique did not significantly affect leak rate.
      Patients with a leak were more likely to require intraoperative transfusion
      (47.1% vs. 24.1%, P = 0.013). As expected, they had a greater prevalence of
      perioperative complications to include pneumonia (38.6% vs. 16.3%, P = 0.001),
      pulmonary embolus (11.3% vs. 4.3%, P = 0.043), ileus (11.4% vs. 1.6%, P =
      0.006%), empyema (11.4% vs. 0%, P > 0.001), and catheter related blood stream
      infections (8.6% vs. 0%, P = 0.001). Despite this increase in perioperative
      morbidity, there was no statistically significant difference in 90 day peri
      operative mortality (2.8% vs. 2.3%) with similar ability to receive adjuvant
      therapy (38.6% vs. 48.0%, P = 0.303), quality of life scores (93.2 vs. 93.1, P =
      0.9), and survival at 12 months (93% vs. 94%, P = 0.3). CONCLUSION: Anastomotic
      leak after oncologic resection does not preclude adjuvant therapy and, when
      managed appropriately, does not affect long term performance status or survival.

PMID- 25873551
TI  - Root hair development in the grasses: what we already know and what we still need
      to know.
AB  - A priority in many crop improvement programs for a long time has been to enhance
      the tolerance level of plants to both abiotic and biotic stress. Recognition that
      the root system is the prime determinant of a plant's ability to extract both
      water and minerals from the soil implies that its architecture is an important
      variable underlying a cultivar's adaptation. The density and/or length of the
      root hairs (RHs) that are formed are thought to have a major bearing on the
      plant's performance under stressful conditions. Any attempt to improve a crop's
      root system will require a detailed understanding of the processes of RH
      differentiation. Recent progress in uncovering the molecular basis of root
      epidermis specialization has been recorded in the grasses. This review seeks to
      present the current view of RH differentiation in grass species. It combines what
      has been learned from molecular-based analyses, histological studies, and
      observation of the phenotypes of both laboratory- and field-grown plants. 

PMID- 25873553
TI  - Large Doses of Vitamin D Fail to Increase 25-Hydroxyvitamin D Levels or to Alter
      Cardiovascular Risk Factors in Obese Adolescents: A Pilot Study.
AB  - PURPOSE: Vitamin D deficiency and cardiometabolic risk factors are common in
      obese adolescents. Observational studies demonstrate an inverse relationship
      among serum 25-hydroxyvitamin D (25OHD) and obesity, insulin resistance, and
      inflammatory cytokines. This pilot study explores if vitamin D supplementation
      could reduce serum concentrations of inflammatory cytokines (interleukin [IL] 6,
      IL-10, tumor necrosis factor alpha), adiponectin, lipids, hemoglobin A1C, and
      high-sensitivity C-reactive protein (hs-CRP). A secondary aim was to determine
      the associations between baseline serum 25OHD concentrations and body mass index
      (BMI), hs-CRP, inflammatory cytokines, and lipids. METHODS: Overweight and obese
      adolescents enrolled in this 24-week, randomized, double-blind study were given
      150,000 IU ergocalciferol or placebo at baseline and 12 weeks. Outcome
      measurements included serum 25OHD, inflammatory cytokines, adiponectin, hs-CRP,
      lipids, hemoglobin A1C, and BMI at baseline, 12, and 24 weeks. RESULTS: Of 40
      participants, 31 (78%) completed the study. Mean +/- standard error 25OHD levels
      were similar in vitamin D and placebo groups at baseline (19.6 +/- 5.3 vs. 25.8
      +/- 10.8 ng/mL) and 24 weeks (20.1 +/- 3.4 vs. 24.6 +/- 8.4 ng/mL). Inflammatory
      and cardiovascular markers were not significantly different between groups at 24
      weeks. Serum 25OHD at baseline was associated with BMI (r = -.44 [95% confidence
      interval, -.66 to -.15]) but not with other outcome measures. CONCLUSIONS:
      Supplementation with vitamin D at 150,000 IU every 3 months failed to increase
      serum 25OHD or alter inflammatory markers and lipids in overweight and obese
      youth. Further studies are needed to establish the dose of vitamin D required to
      increase 25OHD and determine potential effects on metabolic risk factors in obese
      teens.

PMID- 25873552
TI  - Subunit Q Is Required to Stabilize the Large Complex of NADPH Dehydrogenase in
      Synechocystis sp. Strain PCC 6803.
AB  - Two major complexes of NADPH dehydrogenase (NDH-1) have been identified in
      cyanobacteria. A large complex (NDH-1L) contains NdhD1, NdhF1, and NdhP, which
      are absent in a medium size complex (NDH-1M). They play important roles in
      respiration, NDH-1-dependent cyclic electron transport around photosystem I, and
      CO2 uptake. Two mutants sensitive to high light for growth and impaired in cyclic
      electron transport around photosystem I were isolated from the cyanobacterium
      Synechocystis sp. strain PCC 6803 transformed with a transposon-bearing library.
      Both mutants had a tag in an open reading frame encoding a product highly
      homologous to NdhQ, a single-transmembrane small subunit of the NDH-1L complex,
      identified in Thermosynechococcus elongatus by proteomics strategy. Deletion of
      ndhQ disassembled about one-half of the NDH-1L to NDH-1M and consequently
      impaired respiration, but not CO2 uptake. During prolonged incubation of the
      thylakoid membrane with n-dodecyl-beta-D-maltoside at room temperature, the rest
      of the NDH-1L in DeltandhQ was disassembled completely to NDH-1M and was much
      faster than in the wild type. In the ndhP-deletion mutant (DeltandhP) background,
      absence of NdhQ almost completely disassembled the NDH-1L to NDH-1M, similar to
      the results observed in the DeltandhD1/DeltandhD2 mutant. We therefore conclude
      that both NdhQ and NdhP are essential to stabilize the NDH-1L complex.

PMID- 25873554
TI  - Quantitation of sunitinib, an oral multitarget tyrosine kinase inhibitor, and its
      metabolite in urine samples by nonaqueous capillary electrophoresis time of
      flight mass spectrometry.
AB  - A rapid, sensitive, and specific method was developed and validated using a
      nonaqueous-capillary electrophoresis method with TOF-MS for determination of
      sunitinib and N-desethyl sunitinib in human urine. In order to avoid ionic
      suppression a urine samples dilution with methanol 1:10 previous step was used.
      This was the only treatment step to urine samples before the injection. Despite
      this dilution of the urine, the detection limit was as low as 0.07 mg/L for
      sunitinib and 0.15 mg/L for N-desethyl sunitinib. Separation of compounds was
      achieved with a mixture of 5 mM ammonium formate in methanol. The calibration
      curves were linear over the range of 0.5-50.0 mg/L for the two analyzed
      compounds. The within-run and between-run precisions were within 5%, while the
      accuracy ranged from 96.0 to 100.4%. This method can be used in routine clinical
      practice to monitor sunitinib and N-desethyl sunitinib drugs in the urine of
      cancer patients treated with once daily administration. 

PMID- 25873555
TI  - Reducing Cardiovascular and Cancer Risk: How to Address Global Primary Prevention
      in Clinical Practice.
AB  - Emerging evidence suggesting the possibility that interventions able to prevent
      cardiovascular disease (CVD) may also be effective in the prevention of cancer
      have recently stimulated great interest in the medical community. In particular,
      data from both experimental and observational studies have demonstrated that
      aspirin may play a role in preventing different types of cancer. Although the use
      of aspirin in the secondary prevention of CVD is well established, aspirin in
      primary prevention is not systematically recommended because the absolute
      cardiovascular event reduction is similar to the absolute excess in major
      bleedings. By adding to its cardiovascular prevention benefits, the potential
      beneficial effect of aspirin in reducing the incidence of mortality and cancer
      could tip the balance between risks and benefits of aspirin therapy in primary
      prevention in favor of the latter and broaden the indication for treatment with
      aspirin in populations at average risk. Prospective and randomized studies are
      currently investigating the effect of aspirin in prevention of both cancer and
      CVD; however, clinical efforts at the individual level to promote the use of
      aspirin in global (or total) primary prevention already could be made on the
      basis of a balanced evaluation of the benefit/risk ratio. 

PMID- 25873556
TI  - In Situ Catalytic Hydrogenation of Biomass-Derived Methyl Levulinate to gamma
      Valerolactone in Methanol.
AB  - In this work, the hydrocyclization of methyl levulinate (ML) to gamma
      valerolactone (GVL) was performed in MeOH over an in situ prepared nanocopper
      catalyst without external H2 . This nanocopper catalyst served as a dual
      functional catalyst for both hydrogen production by MeOH reforming and
      hydrogenation of ML. Nearly quantitative ML conversion with a GVL selectivity of
      87.6 % was achieved at 240  degrees C in 1 h in MeOH under a nitrogen atmosphere.
      ML in the methanolysis products of cellulose also could be hydrogenated
      effectively to GVL over this nanocopper catalyst even in the presence of humins
      to give an ML conversion of 94.1 % and a GVL selectivity of 73.2 % at 240 
      degrees C in 4 h. The absorption behavior of humins on the surface of the
      nanocopper catalyst was observed, which resulted in a pronounced increase in the
      acidic sites of the nanocopper catalyst that facilitate ring-opening and the
      hydrocarboxylation/alkoxycarbonylation of GVL to byproducts. 

PMID- 25873557
TI  - Transition-metal-free trifluoromethylthiolation of N-heteroarenes.
AB  - A general and efficient methodology for the direct transition metal free
      trifluoromethylthiolation of a broad range of biologically relevant N
      heteroarenes is reported employing abundant sodium chloride as the catalyst. This
      method is operationally simple, exhibits high functional group tolerance, and
      does not require protecting groups. 

PMID- 25873558
TI  - Versatile Viral Vector Strategies for Postscreening Target Validation and RNAi ON
      Target Control.
AB  - Our approach aims to optimize postscreening target validation strategies using
      viral vector-driven RNA interference (RNAi) cell models. The RNAiONE validation
      platform is an array of plasmid-based expression vectors that each drives tandem
      expression of the gene of interest (GOI) with one small hairpin RNA (shRNA) from
      a set of computed candidate sequences. The best-performing shRNA (>85% silencing
      efficiency) is then integrated in an inducible, all-in-one lentiviral vector to
      transduce pharmacologically relevant cell types that endogenously express the
      GOI. VariCHECK is used subsequently to combine the inducible knockdown with an
      equally inducible rescue of the GOI for ON-target phenotype verification. The
      complete RNAiONE-VariCHECK system relies on three key elements to ensure high
      predictability: (1) maximized silencing efficiencies by a focused shRNA
      validation process, (2) homogeneity of the RNAi cell pools by application of
      sophisticated viral vector technologies, and (3) exploiting the advantages of
      inducible expression systems. By using a reversible expression system, our
      strategy adds critical information to hot candidates from RNAi screens and avoids
      potential side effects that may be caused by other, irreversible genomic
      manipulation methods such as transcription activator-like effector nucleases
      (TALEN) or clustered regularly interspaced short palindromic repeats/Cas9
      (CRISPR/Cas). This approach will add credibility to top-hit screening candidates
      and protect researchers from costly misinterpretations early in the preclinical
      drug development process. 

PMID- 25873559
TI  - Making progress with code status documentation.

PMID- 25873560
TI  - Prognostic Value of C-met Expression in Cholangiocarcinoma.
AB  - AIM: To explore the relationship of clinicopathological features and the proteins
      of C-met expression in the prognosis of cholangiocarcinoma. METHODS: Clinical
      data and the completed follow-up information of patients with cholangiocarcinoma
      who underwent cholangiocarcinoma operation from January 2004 to December 2010
      were analyzed retrospectively. The relationship of clinicopathological features
      and C-met in the prognosis of the patients was analyzed. RESULTS: Patients with
      high expression of C-met had significantly shorter overall survival than those
      with low expression of C-met, the difference being statistically significant (P =
      .003). Patients with high C-met expression had significantly shorter disease-free
      survival time than those with low expression of C-met, the difference being
      statistically significant (P = .009). By COX multivariate analysis, high C-met
      expression in tumor tissues was an independent risk factor in predicting overall
      survival and disease-free survival for patients with cholangiocarcinoma (P =
      .038, .048, relative risk = 1.390, 1.427). CONCLUSION: Patients with high C-met
      expression in cancer tissues had shorter disease-free survival and overall
      survival. High expression of C-met is an independent risk factor for overall
      survival and disease-free survival.

PMID- 25873561
TI  - Spanish children are most affected by the economic crisis, says the Spanish
      Society of Public Health (SESPAS).

PMID- 25873562
TI  - Flutamide alters the distribution of c-Src and affects the N-cadherin-beta
      catenin complex in the seminiferous epithelium of adult rat.
AB  - This study was undertaken to explore interactions between c-Src kinase and the N
      cadherin-beta-catenin complex in seminiferous tubules of flutamide-treated rats.
      An anti-androgen flutamide (50 mg/kg bw) was injected daily into adult rats from
      postnatal days 82 to 88. Testes from 90-day-old control and flutamide-treated
      rats were used for experiments. Flutamide did not affect testis morphology, but
      impaired connexin43 immunoexpression between Sertoli cells at the blood-testis
      barrier (BTB) region, indicating the BTB as a sensitive target for flutamide.
      Real-time RT-PCR and western blot analyses revealed upregulation of N-cadherin at
      the mRNA and protein level after flutamide exposure (p < 0.05), whereas no
      changes in beta-catenin and c-Src expression were observed. Notably, membranous
      beta-catenin immunolocalization indicated its involvement in the cell adhesion
      complex rather than its contribution to the Wnt signaling pathway. As we used an
      exposure regime which avoided germ cell loss, it is likely that changes in the N
      cadherin-beta-catenin complex are a primary effect of androgen signaling
      disruption by flutamide. Immunohistochemistry revealed a diffusion of N-cadherin
      and beta-catenin signals away from the BTB with concomitant disruption of c-Src
      staining pattern. As detected by immunofluorescence and coimmunoprecipitation,
      flutamide promoted disassembly of the N-cadherin-beta-catenin complex, induced N
      cadherin to dissociate from c-Src at the BTB site, and altered interactions
      between the cell junction proteins and/or c-Src. Equally important, increased
      levels of p-N-cadherin-Tyr860 and p-beta-catenin-Tyr654 (p < 0.05) pointed to a
      mechanism related to adhesion complex disassembly and suggested a potential role
      of c-Src in the control of the protein-protein dynamics. Overall, for the first
      time we have shown that flutamide alters the distribution of c-Src and affects N
      cadherin-beta-catenin interactions at the BTB. Understanding mechanism(s) by
      which anti-androgens can affect intercellular adhesion within the testis is
      relevant for predicting and preventing reproductive disorders affecting male
      fertility.

PMID- 25873563
TI  - Successional and seasonal variations in soil and litter microbial community
      structure and function during tropical postagricultural forest regeneration: a
      multiyear study.
AB  - Soil microorganisms regulate fundamental biochemical processes in plant litter
      decomposition and soil organic matter (SOM) transformations. Understanding how
      microbial communities respond to changes in vegetation is critical for improving
      predictions of how land-cover change affects belowground carbon storage and
      nutrient availability. We measured intra- and interannual variability in soil and
      forest litter microbial community composition and activity via phospholipid fatty
      acid analysis (PLFA) and extracellular enzyme activity across a well-replicated,
      long-term chronosequence of secondary forests growing on abandoned pastures in
      the wet subtropical forest life zone of Puerto Rico. Microbial community PLFA
      structure differed between young secondary forests and older secondary and
      primary forests, following successional shifts in tree species composition. These
      successional patterns held across seasons, but the microbial groups driving these
      patterns differed over time. Microbial community composition from the forest
      litter differed greatly from those in the soil, but did not show the same
      successional trends. Extracellular enzyme activity did not differ with forest
      succession, but varied by season with greater rates of potential activity in the
      dry seasons. We found few robust significant relationships among microbial
      community parameters and soil pH, moisture, carbon, and nitrogen concentrations.
      Observed inter- and intrannual variability in microbial community structure and
      activity reveal the importance of a multiple, temporal sampling strategy when
      investigating microbial community dynamics with land-use change. Successional
      control over microbial composition with forest recovery suggests strong links
      between above and belowground communities.

PMID- 25873564
TI  - Kinetics and equilibria of the chromatographic separation of maltose and
      trehalose.
AB  - Trehalose, a nonreducing disaccharide, has been extensively applied to food,
      cosmetics, and pharmaceutical goods. The resultant solution of trehalose prepared
      by enzymatic methods includes high amounts of maltose. However, it is quite
      difficult to separate maltose and trehalose on an industrial scale because of
      their similar properties. In this paper, a high-performance resin was selected as
      a stationary phase to separate trehalose and maltose, and the resolution of these
      sugars was 0.59. The potential of a cation exchange resin was investigated as the
      stationary phase in separating trehalose and maltose using deionized water as the
      mobile phase. Based on the equilibrium dispersive model, the axial dispersion
      coefficients and overall mass transfer coefficients of maltose and trehalose were
      determined by moment analysis at two different temperatures, 50 and 70 degrees C.
      Other parameters, including the column void and the adsorption isotherms, were
      also determined and applied to simulate the elution curves of trehalose and
      maltose. The simulated results matched the experimental data, validating the
      parameters. The optimized parameters are critical to the chromatographic
      separation of trehalose and maltose on an industrial scale. 

PMID- 25873565
TI  - Utility of gold nanoparticles in luminescence determination of trovafloxacin:
      comparison of chemiluminescence and fluorescence detection.
AB  - Two novel sensitive sequential injection chemiluminescence analysis and
      fluorescence methods for trovafloxacin mesylate detection have been developed.
      The methods were based on the enhancement effect of gold nanoparticles on luminol
      ferricyanide-trovafloxacin and europium(III)-trovafloxacin complex systems. The
      optimum conditions for both detection methods were investigated. The
      chemiluminescence signal was emitted due to the enhanced effect of gold
      nanoparticles on the reaction of luminol-ferricyanide-trovafloxacin in an
      alkaline medium. The response was linear over a concentration range of 1.0 * 10(
      9) to 1.0 * 10(-2) mol/L (%RSD = 1.3), (n = 9, r = 0.9991) with a detection limit
      of 1.7 * 10(-10) mol/L (S/N = 3). The weak fluorescence intensity signal of the
      oxidation complex of europium(III)-trovafloxacin was strongly enhanced by gold
      nanoparticles and detected at lambdaex = 330 and lambdaem = 540 nm. Fluorescence
      detection enabled the determination of trovafloxacin mesylate over a linear range
      of 1.0 * 10(-8) to 1.0 * 10(-3) mol/L (%RSD = 1.2), (n = 6, r = 0.9993) with a
      detection limit of 3.3 * 10(-9) mol/L. The proposed methods were successfully
      applied to the determination of the studied drug in its bulk form and in
      pharmaceutical preparations. The results were treated statistically and compared
      with those obtained from other reported methods.

PMID- 25873566
TI  - Anion-dipole interactions make the homopolymers self-assemble into multiple
      nanostructures.
AB  - Anion-dipole interactions can make homopolymers self-assemble like an amphiphilic
      block copolymer. Generally, common homopolymers cannot self-assemble into
      multiple nanostructures. Here, it is reported that anion-dipole interactions can
      enable a number of homopolymers to achieve a variety of self-assembly behaviors
      in aqueous solution. Such interactions and self-assembly features have been
      exclusively reserved for amphiphilic (block) polymers until now. 

PMID- 25873567
TI  - Enzymatic transformations involved in the biosynthesis of microbial exo
      polysaccharides based on the assembly of repeat units.
AB  - Microbial exo-polysaccharides can serve as valuable biopolymers in medicine, food
      and the feed industry as well as in various technical applications as substitutes
      of petro-based polymers or with unusual performance. Due to their different
      natural functions, they have vastly diverse structures, which lead to a very
      different properties. This structural diversity is brought about by complex
      biosyntheses based on enzymes whose genes are mostly encoded in clusters within
      the genomes of the different microbial species. The organisation of the genes and
      the chemical structures of the corresponding polysaccharides are closely related.
      Here, we will mainly focus on the genetics and biosynthesis of some major
      bacterial hetero-polysaccharides that are based on repeat unit assembly and will
      present specific examples of enzymatic transformation steps. Finally, a short
      outlook will be given on how in vivo modifications based on enzymatic
      transformations could be used to engineer these polymers.

PMID- 25873568
TI  - Electron-phonon interaction and thermal boundary resistance at the interfaces of
      Ge2Sb2Te5 with metals and dielectrics.
AB  - The Ge2Sb2Te5 compound is of interest for applications in phase change non
      volatile memories. First-principles calculations of phonon dispersion relations
      and electron-phonon coupling constant provide an estimate of the electron-phonon
      contribution to the thermal boundary resistance at the interfaces of Ge2Sb2Te5
      with dielectrics (silica) and metal electrodes (Al and TiN). The diffuse mismatch
      model including full phononic dispersion has been used to compute the phononic
      contribution to the thermal boundary resistance. The calculated value of the
      electron-phonon contribution to the TBR at 300 K of about 14 m(2)K GW(-1) would
      dominate the TBR at the interfaces of hexagonal Ge2Sb2Te5 with the surrounding
      dielectrics and metals considered here once interdiffusion at the boundaries
      could be minimized. 

PMID- 25873570
TI  - Metabolic syndrome in adult survivors of childhood cancer: the intersection of
      oncology, endocrinology, and cardiology.

PMID- 25873571
TI  - Cancer treatment and gonadal function: experimental and established strategies
      for fertility preservation in children and young adults.
AB  - Preservation of gonadal function is an important priority for the long-term
      health of cancer survivors of both sexes and all ages at treatment. Loss of
      opportunity for fertility is a prime concern in both male and female cancer
      survivors, but endocrine effects of gonadal damage are likewise central to long
      term health and wellbeing. Some fertility preservation techniques, such as semen
      and embryo cryopreservation, are established and successful in adults, and
      development of oocyte vitrification has greatly improved the potential to
      cryopreserve unfertilised oocytes. Despite being recommended for all pubertal
      male patients, sperm banking is not universally practised in paediatric oncology
      centres, and very few adolescent-friendly facilities exist. All approaches to
      fertility preservation have specific challenges in children and teenagers,
      including ethical, practical, and scientific issues. For young women,
      cryopreservation of ovarian cortical tissue with later replacement has resulted
      in at least 40 livebirths, but is still regarded as experimental in most
      countries. For prepubertal boys, testicular biopsy cryopreservation is offered in
      some centres, but how that tissue might be used in the future is unclear, and so
      far no evidence suggests that fertility can be restored. For both sexes, these
      approaches involve an invasive procedure and have an uncertain risk of tissue
      contamination in haematological and other malignancies. Decision making for all
      these approaches needs assessment of the individual's risk of fertility loss, and
      is made at a time of emotional distress. Development of this specialty needs
      better provision of information for patients and their medical teams, and
      improvements in service provision, to match technical and scientific advances. 

PMID- 25873569
TI  - Screening and management of adverse endocrine outcomes in adult survivors of
      childhood and adolescent cancer.
AB  - 5 year survival for childhood and adolescent cancer in developed countries is now
      in excess of 80% and the number of survivors of cancer continues to increase
      worldwide. After completion of therapy, many of these survivors will face a
      lifelong risk of endocrine late effects. We summarise the available evidence
      related to the prevalence and risk factors for endocrine late effects among adult
      survivors of childhood and adolescent cancer. Present screening, surveillance,
      and treatment recommendations differ by country and region, so we also highlight
      the continued effort to harmonise the international guidelines for this
      population. 

PMID- 25873572
TI  - Effect of cancer treatment on hypothalamic-pituitary function.
AB  - The past 30 years have seen a great improvement in survival of children and young
      adults treated for cancer. Cancer treatment can put patients at risk of health
      problems that can develop many years later, most commonly affecting the endocrine
      system. Patients treated with cranial radiotherapy often develop dysfunction of
      the hypothalamic-pituitary axis. A characteristic pattern of hormone deficiencies
      develops over several years. Growth hormone is disrupted most often, followed by
      gonadal, adrenal, and thyroid hormones, leading to abnormal growth and puberty in
      children, and affecting general wellbeing and fertility in adults. The severity
      and rate of development of hypopituitarism is determined by the dose of
      radiotherapy delivered to the hypothalamic-pituitary axis. Individual growth
      hormone deficiencies can develop after a dose as low as 10 Gy, whereas multiple
      hormone deficiencies are common after 60 Gy. New techniques in radiotherapy aim
      to reduce the effect on the hypothalamic-pituitary axis by minimising the dose
      received. Patients taking cytotoxic drugs do not often develop overt
      hypopituitarism, although the effect of radiotherapy might be enhanced. The
      exception is adrenal insufficiency caused by glucocorticosteroids which, although
      transient, can be life-threatening. New biological drugs to treat cancer can
      cause autoimmune hypophysitis and hypopituitarism; therefore, oncologists and
      endocrinologists should be vigilant and work together to optimise patient
      outcomes. 

PMID- 25873573
TI  - Bone health in survivors of childhood cancer.

PMID- 25873575
TI  - Legal system distorts reality by focusing on a single error in untoward
      incidents, conference hears.

PMID- 25873574
TI  - Variability in surgical quality in a phase III clinical trial of radical
      cystectomy in patients with organ-confined, node-negative urothelial carcinoma of
      the bladder.
AB  - BACKGROUND AND OBJECTIVES: Previous studies have shown that variability in
      surgical technique can affect the outcomes of cooperative group trials. We
      analyzed measures of surgical quality and clinical outcomes in patients enrolled
      in the p53-MVAC trial. METHODS: We performed a post-hoc analysis of patients with
      pT1-T2N0M0 urothelial carcinoma of the bladder following radical cystectomy (RC)
      and bilateral pelvic and iliac lymphadenectomy (LND). Measures of surgical
      quality were examined for associations with time to recurrence (TTR) and overall
      survival (OS). RESULTS: We reviewed operative and/or pathology reports for 440
      patients from 35 sites. We found that only 31% of patients met all suggested
      trial eligibility criteria of having >=15 lymph nodes identified in the
      pathologic specimen (LN#) and having undergone both extended and presacral LND.
      There was no association between extent of LND, LN#, or presacral LND and TTR or
      OS after adjustment for confounders and multiple testing. CONCLUSIONS: We
      demonstrated that there was substantial variability in surgical technique within
      a cooperative group trial. Despite explicit entry criteria, many patients did not
      undergo per-protocol LNDs. While outcomes were not apparently affected, it is
      nonetheless evident that careful attention to study design and quality monitoring
      will be critical to successful future trials.

PMID- 25873576
TI  - Cases of Ebola virus disease predicted to rise from hundreds to thousands per
      week unless control measures improve.

PMID- 25873577
TI  - African Americans and Hispanics Remain at Lower Risk of Ovarian Cancer Than Non
      Hispanic Whites after Considering Nongenetic Risk Factors and Oophorectomy Rates.
AB  - BACKGROUND: Risk factors for invasive epithelial ovarian cancer (IEOC) among
      Hispanics and African Americans are understudied despite notable differences in
      incidence relative to non-Hispanic whites. METHODS: We used multivariate logistic
      regression to examine parity, oral contraceptive use, tubal ligation,
      endometriosis, family history of ovarian cancer, and talc use and risk of IEOC
      among Hispanics (308 cases and 380 controls), African Americans (128 cases and
      143 controls), and non-Hispanic whites (1,265 cases and 1,868 controls) using
      four case-control studies we conducted in Los Angeles County. We expressed each
      of these factors in the form of increasing risk and calculated population
      attributable risk percentage (PAR%) estimates for the six risk factors separately
      and jointly in the three groups. RESULTS: The risk associations with these six
      well-accepted factors were comparable in the three groups. The significant
      racial/ethnic differences in the prevalence of these factors and differences in
      their oophorectomy rates explained 31% of the lower incidence in African
      Americans compared with non-Hispanic whites, but only 13% of the lower incidence
      in Hispanics. The PAR%s ranged from 27.5% to 31.0% for no tubal ligation, 15.9%
      to 22.2% for not using oral contraceptives, and 12.2% to 15.1% for using talc in
      the three groups. CONCLUSIONS: All six risk factors are comparably important in
      the three groups. Differences in the prevalence of these factors and their
      oophorectomy rates explained approximately one third of the difference in
      incidence between African Americans and non-Hispanic whites. IMPACT: Devising
      strategies to lessen the burden of IEOC will be applicable to all three
      racial/ethnic groups.

PMID- 25873578
TI  - Carotenoid Intake from Natural Sources and Head and Neck Cancer: A Systematic
      Review and Meta-analysis of Epidemiological Studies.
AB  - Because of their role as antioxidants, the intake of carotenoids has been
      hypothesized to reduce the risk of head and neck cancer (HNC). We conducted a
      systematic review and meta-analysis of the epidemiological studies to investigate
      whether the intake of specific carotenoids from dietary sources, as well as
      combined carotenoids, is associated with the risk of HNC according to cancer
      subsites. A comprehensive literature search of the Medline and Scopus databases
      was conducted. Sixteen articles were identified from the literature search, of
      which 15 were case-control studies and one prospective cohort study. The risk
      reduction associated with beta-carotene equivalents intake was 46% (95% CI, 20%
      63%) for cancer of oral cavity and 57% (95% CI, 23%-76%) for laryngeal cancer.
      Lycopene and beta-cryptoxanthin also reduced the risk for laryngeal cancer; the
      ORs for the highest category compared with the lowest one of carotenoid intake
      were 50% (95% CI, 11%-72%) and 59% (95% CI, 49%-67%), respectively. Lycopene,
      alpha-carotene, and beta-cryptoxanthin were associated with at least 26%
      reduction in the rate of oral and pharyngeal cancer (95% CI, 2%-44%). Our
      systematic review and meta-analysis on dietary carotenoids intake and HNC showed
      carotenoids to act protectively against HNC, in relation to most of single
      nutrients and subsites.

PMID- 25873579
TI  - Identification of culturable vaginal Lactobacillus species among reproductive age
      women in Mysore, India.
AB  - A healthy vaginal environment is predominated by certain Lactobacillus species,
      which lead to the prevention of infections of the reproductive tract. This study
      examined the characteristics of cultivable Lactobacillus species in both healthy
      women and women with bacterial vaginosis (BV). Between November 2011 and
      September 2013, 139 women attending a women's clinic in Mysore, India, were
      evaluated for BV in a cross-sectional study. BV was diagnosed using Amsel's
      criteria: homogeneous vaginal discharge, vaginal pH >4.5, production of amines,
      and presence of "clue" cells. Those with three or more of the characteristics
      were considered to have BV. Vaginal swabs were then cultured in Rogosa agar and
      de Man-Rogosa-Sharpe broth. Gram-positive lactobacilli generating 600-800 bp
      amplicons by 16 sRNA were further characterized by sequencing. Cultivable vaginal
      samples were obtained from 132 women (94.9%). According to the Amsel criteria, 83
      women (62.1%) were healthy, and 49 (37.1%) had BV. Eleven different Lactobacillus
      species were isolated from 47 women. The common lactobacilli species found in
      this sample included L. crispatus (39.6%), L. gasseri (45.8%), and L. jensenii
      (14.6%). Lactobacilli were isolated from 39 healthy women and eight with BV. L.
      gasseri was cultured from 18.8% of healthy women and 6.1% with BV. The presence
      of L. reuteri was significantly associated with normal vaginal microbiota (P
      value = 0.026). These results further our understanding of vaginal lactobacilli
      colonization and richness in this particular population. Our findings showed that
      lactobacilli species present in the vaginas of healthy women in India do not
      differ from those reported from other countries.

PMID- 25873580
TI  - Accuracy of in vitro susceptibility tests for carbapenemase-producing Gram
      negative bacteria.
AB  - Accurate susceptibility results on antibiotic-resistant bacteria are essential
      for proper treatment of infections. In this study, 100 metallo-beta-lactamase
      (MBL)-producing strains and 95 isolates with Klebsiella pneumoniae carbapenemase
      (KPC) were tested for carbapenem susceptibility using two automated platforms,
      the Phoenix and Vitek-2 systems, and a manual Etest. Phoenix showed higher
      categorical agreements (97% for imipenem and 94% for meropenem) compared with
      those from Vitek-2 (92 and 74%) and Etest (89 and 96%), respectively, when
      testing MBL strains. Categorical agreement for imipenem tests with KPC-producing
      strains was 88.4% with the Phoenix system, 83.2% with the Vitek 2 system and
      90.5% with the Etest. Categorical agreement was 100% for all tests with
      ertapenem. In conclusion, the Phoenix system demonstrated a higher accuracy than
      Vitek-2 in testing carbapenemase-producing strains, particularly in MBL strains.

PMID- 25873581
TI  - Prevalence of eight resistance-nodulation-division efflux pump genes in
      epidemiologically characterized Acinetobacter baumannii of worldwide origin.
AB  - The increasing emergence of multidrug-resistant Acinetobacter baumannii
      constitutes a worldwide threat in hospital settings. Efflux-mediated resistance,
      particularly the resistance-nodulation-division (RND)-type efflux pumps,
      contributes significantly to decreased susceptibility to multiple antibiotics
      when overexpressed. Using PCR-based detection, the prevalence of genes encoding
      the RND efflux pumps AdeB, AdeJ and AdeG was investigated amongst 144
      epidemiologically characterized and geographically diverse A. baumannii isolates
      of worldwide origin, representing International Clones 1-8 and genotypically
      unique isolates. Furthermore, five putative RND-type efflux genes identified via
      an in silico approach were included. Five of the eight investigated efflux pump
      genes were present in all isolates, including adeJ and adeG; the prevalence of
      the others varied between 65 and 97%. No association between the presence of one
      or multiple pumps to a specific clonal lineage was detected. The high prevalence
      of the efflux pump genes supports a fixed function of each individual pump that
      is not yet fully understood.

PMID- 25873582
TI  - Clinical and laboratory features parameters of human granulocytic anaplasmosis
      (HGA) in patients admitted to hospital in Guangdong Province, China.
AB  - BACKGROUND: Human granulocytic anaplasmosis (HGA) is an acute tick-borne
      infectious disease with increasing morbidity and mortality, but is rarely
      considered in clinical practice. Because human-to-human transfusion or nosocomial
      transmission can occur, diagnosis is difficult when the history of tick bites is
      not clear. METHODS: We present clinical features and laboratory data of HGA
      patients who had no clear tick bite history. RESULTS: All patients in the study
      presented with a high fever, petechiae, purpura, nose bleeding and leukopenia,
      and patients had abnormally high levels of serum ferritin and C-reactive protein.
      Morulae in leukocytes were observed in three patients. Foamy histiocytes and
      slight erythrophagocytic activity were only found in severely ill patients.
      CONCLUSION: In patients with fever and thrombocytopenia in whom no other
      diagnosis is evident on clinical assessment, HGA should be considered in the
      differential diagnosis, and tested for serologically if possible. For patients in
      whom the diagnosis of HGA is possible, and to whom tetracyclines can safely be
      given, it is apparent that these drugs hasten recovery and improve the prognosis.

PMID- 25873584
TI  - Diversity of metabolic profiles of cystic fibrosis Pseudomonas aeruginosa during
      the early stages of lung infection.
AB  - Pseudomonas aeruginosa is the dominant pathogen infecting the airways of cystic
      fibrosis (CF) patients. During the intermittent colonization phase, P. aeruginosa
      resembles environmental strains but later evolves to the chronic adapted
      phenotype characterized by resistance to antibiotics and mutations in the global
      regulator genes mucA, lasR and rpoN. Our aim was to understand the metabolic
      changes occurring over time and between niches of the CF airways. By applying
      Phenotype MicroArrays, we investigated changes in the carbon and nitrogen
      catabolism of subsequently clonally related mucoid and non-mucoid (NM) lung and
      sinus P. aeruginosa isolates from 10 CF patients (five intermittently
      colonized/five chronically infected). We found the most pronounced catabolic
      changes for the early/late NM isolate comparisons, with respiratory reduction
      seen for all chronically infecting isolates and two intermittently colonizing
      isolates. Fewer differences were observed between sinus and lung isolates,
      showing a higher degree of isolate similarity between these two niches. Modest
      respiratory changes were seen for the early isolate/PAO1 comparisons, indicating
      colonization with environmental isolates. Assignment of metabolic pathways via
      the KEGG database showed a prevalence of substrates involved in the metabolism of
      Ala, Asp and Glu, d-Ala, and Arg and Pro. In conclusion, extensive heterogeneity
      in the metabolic profiles of the P. aeruginosa isolates was observed from the
      initial stages of the infection, showing a rapid diversification of the bacteria
      in the heterogeneous environment of the lung. Metabolic reduction seems to be a
      common trait and therefore an adaptive phenotype, though it can be reached via
      multiple metabolic pathways. 

PMID- 25873583
TI  - Sensor-response regulator interactions in a cross-regulated signal transduction
      network.
AB  - Two-component signal transduction involves phosphoryl transfer between a
      histidine kinase sensor and a response regulator effector. The nitrate-responsive
      two-component signal transduction systems in Escherichia coli represent a
      paradigm for a cross-regulation network, in which the paralogous sensor-response
      regulator pairs, NarX-NarL and NarQ-NarP, exhibit both cognate (e.g. NarX-NarL)
      and non-cognate (e.g. NarQ-NarL) interactions to control output. Here, we
      describe results from bacterial adenylate cyclase two-hybrid (BACTH) analysis to
      examine sensor dimerization as well as interaction between sensor-response
      regulator cognate and non-cognate pairs. Although results from BACTH analysis
      indicated that the NarX and NarQ sensors interact with each other, results from
      intragenic complementation tests demonstrate that they do not form functional
      heterodimers. Additionally, intragenic complementation shows that both NarX and
      NarQ undergo intermolecular autophosphorylation, deviating from the previously
      reported correlation between DHp (dimerization and histidyl phosphotransfer)
      domain loop handedness and autophosphorylation mode. Results from BACTH analysis
      revealed robust interactions for the NarX-NarL, NarQ-NarL and NarQ-NarP pairs but
      a much weaker interaction for the NarX-NarP pair. This demonstrates that
      asymmetrical cross-regulation results from differential binding affinities
      between different sensor-regulator pairs. Finally, results indicate that the NarL
      effector (DNA-binding) domain inhibits NarX-NarL interaction. Missense
      substitutions at receiver domain residue Ser-80 enhanced NarX-NarL interaction,
      apparently by destabilizing the NarL receiver-effector domain interface. 

PMID- 25873585
TI  - Adrenergic antagonists restrict replication of Legionella.
AB  - Legionella pneumophila is a facultative intracellular bacterium, which upon
      inhalation can cause a potentially fatal pneumonia termed Legionnaires' disease.
      The opportunistic pathogen grows in environmental amoebae and mammalian
      macrophages within a unique membrane-bound compartment, the 'Legionella
      containing vacuole'. Bacteria are exposed to many environmental cues including
      small signalling molecules from eukaryotic cells. A number of pathogenic bacteria
      sense and respond to catecholamine hormones, such as adrenalin and noradrenalin,
      a process mediated via the QseBC two-component system in some bacteria. In this
      study, we examined the effect of adrenergic compounds on L. pneumophila, and
      discovered that the adrenergic receptor antagonists benoxathian, naftopidil,
      propranolol and labetalol, as well as the QseC sensor kinase inhibitor LED209,
      reduced the growth of L. pneumophila in broth or amoebae, while replication in
      macrophages was enhanced. Growth restriction was common to members of the genus
      Legionella and Mycobacterium, and was observed for L. pneumophila in the
      replicative but not stationary phase of the biphasic life cycle. Deletion of the
      L. pneumophila qseBC genes indicated that growth inhibition by adrenergics or
      LED209 is mediated only to a minor extent by this two-component system, implying
      the presence of other adrenergic sensing systems. This study identifies
      adrenergic molecules as novel inhibitors of extra- and intracellular growth of
      Legionella and reveals LED209 as a potential lead compound to combat infections
      with Legionella or Mycobacterium spp. 

PMID- 25873586
TI  - The Emerging Molecular Foundations of Pediatric Brain Tumors.
AB  - Recent years have witnessed extensive molecular characterization of several
      pediatric brain tumor variants. These studies have dramatically shifted notions
      of disease classification and are likely to have similarly profound effects on
      patient management in the near future. In this review, we cover the molecular
      foundations of low-grade glial and glioneuronal neoplasms, high-grade glioma,
      ependymoma, and medulloblastoma, the details of which have only been recently
      elucidated in many cases. In doing so, we describe an array of biomarkers likely
      to play a major role in clinically relevant molecular stratification moving
      forward. We also discuss strategies for robust and efficient biomarker assessment
      in the clinical environment. 

PMID- 25873587
TI  - The Relationship Among Genetic Heritability, Environmental Effects, and Autism
      Spectrum Disorders: 37 Pairs of Ascertained Twin Study.
AB  - Autism spectrum disorders (ASD) comprise a heterogeneous group of
      neurodevelopmental disorders that have strong heritability. To better understand
      the heritable factors in twins with clinically diagnosed ASD and to discuss the
      relationship between social impairments and genetic and environmental factors. In
      last 13 years, over 12,000 cases of ASD were diagnosed in the children's
      development and behavior center, the authors review 37 pairs of these twins, in
      each pair, and at least 1 twin had been diagnosed with an ASD, and found that the
      concordance rate was 80% [95% confidence interval (CI) 51.9-95.7%] for
      monozygotic twins and 13.6% (95% CI: 2.9-34.9%) for dizygotic twins. The
      heritability of social impairments for ASD was 60.9% (95% CI: 47.3-74.5%). In
      addition, the rate of nonshared environmental factors was 39.1% (95% CI: 25.5
      52.7%), and there were no shared environmental effects. Genetics and special
      environmental effect play an important role on ASD social impairments. 

PMID- 25873589
TI  - A Phylogenetic Analysis of 34 Chloroplast Genomes Elucidates the Relationships
      between Wild and Domestic Species within the Genus Citrus.
AB  - Citrus genus includes some of the most important cultivated fruit trees
      worldwide. Despite being extensively studied because of its commercial relevance,
      the origin of cultivated citrus species and the history of its domestication
      still remain an open question. Here, we present a phylogenetic analysis of the
      chloroplast genomes of 34 citrus genotypes which constitutes the most
      comprehensive and detailed study to date on the evolution and variability of the
      genus Citrus. A statistical model was used to estimate divergence times between
      the major citrus groups. Additionally, a complete map of the variability across
      the genome of different citrus species was produced, including single nucleotide
      variants, heteroplasmic positions, indels (insertions and deletions), and large
      structural variants. The distribution of all these variants provided further
      independent support to the phylogeny obtained. An unexpected finding was the high
      level of heteroplasmy found in several of the analyzed genomes. The use of the
      complete chloroplast DNA not only paves the way for a better understanding of the
      phylogenetic relationships within the Citrus genus but also provides original
      insights into other elusive evolutionary processes, such as chloroplast
      inheritance, heteroplasmy, and gene selection. 

PMID- 25873590
TI  - The dJ/dS Ratio Test Reveals Hundreds of Novel Putative Cancer Drivers.
AB  - Computational tools with a balanced sensitivity and specificity in identification
      of candidate cancer drivers are highly desired. In this study, we propose a new
      statistical test, namely the dJ/dS ratio test, to compute the relative mutation
      rate of exon/intron junction sites (dJ) to synonymous sites (dS); observation of
      dJ/dS ratio larger than 1 in cancer indicates positive selection for splicing
      deregulation, a signature of cancer driver genes. Using this method, we analyzed
      the data from The Cancer Genome Atlas and identified hundreds of novel putative
      cancer drivers. Interestingly, these genes are highly enriched in biological
      processes related to the development and maintenance of multicellularity,
      paralleling a previous finding that cancer evolves back to be unicellular by
      knocking down the multicellularity-associated genetic network. 

PMID- 25873591
TI  - Migraine phenotype in patients with a dual versus single parent history.

PMID- 25873593
TI  - Sexual Violence Experienced in the Sport Context by a Representative Sample of
      Quebec Adolescents.
AB  - This is the first study to report the prevalence of sexual violence perpetrated
      by a sport coach within a representative sample of the general population of
      adolescents aged between 14 and 17 years (N = 6,450). The questionnaire
      administered in high schools includes self-reported measures on a variety of
      dimensions relevant to the study of victimization, including sexual abuse, sexual
      contacts perceived as consensual, sexual harassment, and involvement in an
      organized sport context. Descriptive and chi-square analyses were performed. The
      results show that 0.5% of adolescents experienced sexual abuse involving a coach.
      When considering all adolescents who experienced sexual abuse in their lifetime
      (10.2%), it appears that 5.3% of them were victims of sexual abuse by a coach.
      Participants also reported experiencing sexual harassment from a coach (0.4%) and
      consensual sexual contacts (1.2%) with a coach in the 12 months preceding the
      study. Questions are raised on the overrepresentation of boys in situations of
      sexual victimization experiences in an organized sport context.

PMID- 25873592
TI  - The Novel ATP-Competitive MEK/Aurora Kinase Inhibitor BI-847325 Overcomes
      Acquired BRAF Inhibitor Resistance through Suppression of Mcl-1 and MEK
      Expression.
AB  - Resistance to BRAF inhibitors is a major clinical problem. Here, we evaluate BI
      847325, an ATP-competitive inhibitor of MEK and Aurora kinases, in treatment
      naive and drug-resistant BRAF-mutant melanoma models. BI-847325 potently
      inhibited growth and survival of melanoma cell lines that were both BRAF
      inhibitor naive and resistant in 2D culture, 3D cell culture conditions, and in
      colony formation assays. Western blot studies showed BI-847325 to reduce
      expression of phospho-ERK and phospho-histone 3 in multiple models of vemurafenib
      resistance. Mechanistically, BI-847325 decreased the expression of MEK and Mcl-1
      while increasing the expression of the proapoptotic protein BIM. Strong
      suppression of MEK expression was observed after 48 hours of treatment, with no
      recovery following >72 hours of washout. siRNA-mediated knockdown of Mcl-1
      enhanced the effects of BI-847325, whereas Mcl-1 overexpression reversed this in
      both 2D cell culture and 3D spheroid melanoma models. In vivo, once weekly BI
      847325 (70 mg/kg) led to durable regression of BRAF-inhibitor naive xenografts
      with no regrowth seen (>65 days of treatment). In contrast, treatment with the
      vemurafenib analog PLX4720 was associated with tumor relapse at >30 days. BI
      847325 also suppressed the long-term growth of xenografts with acquired PLX4720
      resistance. Analysis of tumor samples revealed BI-847325 to induce apoptosis
      associated with suppression of phospho-ERK, total MEK, phospho-Histone3, and Mcl
      1 expression. Our studies indicate that BI-847325 is effective in overcoming BRAF
      inhibitor resistance and has long-term inhibitory effects upon BRAF-mutant
      melanoma in vivo, through a mechanism associated with the decreased expression of
      both MEK and Mcl-1.

PMID- 25873594
TI  - Ligand Selectivity among the Dopamine and Serotonin Transporters Specified by the
      Forward Binding Reaction.
AB  - The membrane transporters for the monoamines serotonin (SERT) and dopamine (DAT)
      are prominent targets of various psychoactive substances, including competitive
      inhibitors, such as tricyclic antidepressants, methylphenidate, and cocaine. Upon
      rapid application of a substrate, SERT and DAT display an inwardly directed
      current comprised of a peak and a steady-state component. Binding of a
      competitive inhibitor to the transporter leads to reduction of the peak current
      amplitude because occupancy of the transporter by an inhibitor prevents the
      induction of the peak current by the substrate. We show that the inhibitory
      effect on the peak current can be used to study the association rate constant
      (k(on)), dissociation rate constant (k(off)), and equilibrium dissociation
      constant (K(D)) of chemically distinct SERT and DAT inhibitors, with high
      temporal precision and without the need of high-affinity radioligands as
      surrogates. We exemplify our approach by measuring the kinetics of cocaine,
      methylphenidate, and desipramine binding to SERT and DAT. Our analysis revealed
      that the selectivity of methylphenidate and desipramine for DAT and SERT,
      respectively, can be accounted for by their rate of association and not by the
      residence time in their respective binding sites.

PMID- 25873595
TI  - Evidence-base for Fever interventions following stroke.

PMID- 25873596
TI  - Organizational update: the world health organization global status report on
      noncommunicable diseases 2014; one more landmark step in the combat against
      stroke and vascular disease.

PMID- 25873597
TI  - Hypoxic viable tissue in human chronic cerebral ischemia because of unilateral
      major cerebral artery steno-occlusive disease.
AB  - BACKGROUND AND PURPOSE: Positron emission tomography (PET) with radiolabeled 2
      nitroimidazoles directly detects hypoxic but viable tissue present in an acute
      ischemic area in the human brain. This study using PET with 1-(2-(18)F-fluoro-1
      [hydroxymethyl]ethoxy) methyl-2-nitroimidazole ((18)F-FRP170) aimed to determine
      whether tissue with an abnormally elevated uptake of (18)F-FRP170 exists in human
      chronic cerebral ischemia because of unilateral atherosclerotic major cerebral
      artery steno-occlusive disease. METHODS: (18)F-FRP170 PET was performed, and
      cerebral blood flow and metabolism were assessed using (15)O-gas PET in 20
      healthy subjects and 52 patients. A region of interest (ROI) was automatically
      placed in 3 segments of the middle cerebral artery territory in both cerebral
      hemispheres with a 3-dimensional stereotaxic ROI template using SPM2, and each
      PET value was determined in each ROI. The ratio of values in the affected versus
      contralateral hemispheres was calculated for the (18)F-FRP170 PET image. RESULTS:
      A significant correlation was observed between oxygen extraction fraction and
      (18)F-FRP170 ratios (rho=0.509; P<0.0001) in a total of 156 ROIs in 52 patients.
      The specificity and positive-predictive value for a combination of an elevated
      oxygen extraction fraction and a moderately reduced cerebral oxygen metabolism
      for detection of an abnormally elevated (18)F-FRP170 ratio (19 ROIs: 12%) were
      significantly greater than those for the individual categories (elevated oxygen
      extraction fraction, moderately reduced cerebral oxygen metabolism, or reduced
      cerebral blood flow). CONCLUSIONS: Tissues with abnormally elevated uptake of
      (18)F-FRP170 exist in human chronic cerebral ischemia characterized by a
      combination of misery perfusion and moderately reduced oxygen metabolism because
      of unilateral atherosclerotic major cerebral artery steno-occlusive disease.

PMID- 25873599
TI  - Letter by Bosche and Macdonald regarding article, "relevance of blood-brain
      barrier disruption after endovascular treatment of ischemic stroke: dual-energy
      computed tomographic study".

PMID- 25873600
TI  - Prehospital reversal of warfarin-related coagulopathy in intracerebral hemorrhage
      in a mobile stroke treatment unit.

PMID- 25873601
TI  - Acupuncture efficacy on ischemic stroke recovery: multicenter randomized
      controlled trial in China.
AB  - BACKGROUND AND PURPOSE: Acupuncture is a frequently used complementary treatment
      for ischemic stroke in China but the evidence available from previous randomized
      trials is inconclusive. The objective of this study was to assess the efficacy
      and safety of acupuncture in a more robustly designed larger scale trial.
      METHODS: This is a multicenter, single-blinded, randomized controlled trial.
      Eight hundred sixty-two hospitalized patients with limb paralysis between 3 to 10
      days after ischemic stroke onset were allocated acupuncture plus standard care or
      standard care alone. The acupuncture was applied 5 times per week for 3 to 4
      weeks. The primary outcomes were defined as follows: (1) death/disability
      according to Barthel index and (2) death/institutional care at 6 months. RESULTS:
      There was a tendency of fewer patients being dead or dependent in acupuncture
      group (80/385, 20.7%) than in control group (102/396, 25.8%) at 6 months (odds
      ratio, 0.75; 95% confidence interval, 0.54-1.05). The benefit was noted in
      subgroup receiving >=10 sessions of acupuncture (odds ratio, 0.68; 95% confidence
      interval, 0.47-0.98). There was no statistical difference in death or
      institutional care between the 2 groups (odds ratio, 1.06; 95% confidence
      interval, 0.63-1.79). Severe adverse events occurred in 7.6% and 8.3% of patients
      in the 2 groups, respectively. CONCLUSIONS: Acupuncture seemed to be safe in the
      subacute phase of ischemic stroke. If the potential benefits observed are
      confirmed in future larger study, the health gain from wider use of the treatment
      could be substantial. CLINICAL TRIAL REGISTRATION: URL:
      http://www.chictr.org/en/. Unique identifier: ChiCTR-TRC-11001353.

PMID- 25873603
TI  - An update on heart failure and peripheral arterial disease.

PMID- 25873602
TI  - Premature ventricular complexes on screening electrocardiogram and risk of
      ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Premature ventricular complexes (PVCs) detected from long
      term ECG recordings have been associated with an increased risk of ischemic
      stroke. Whether PVCs seen on routine ECG, commonly used in clinical practice, are
      associated with an increased risk of ischemic stroke remains unstudied. METHODS:
      This analysis included 24 460 participants (aged, 64.5+9.3 years; 55.1% women;
      40.0% blacks) from the Reasons for Geographic and Racial Differences in Stroke
      (REGARDS) study who were free of stroke at the time of enrollment. PVCs were
      ascertained from baseline ECG (2003-2007), and incident stroke cases through 2011
      were confirmed by an adjudication committee. RESULTS: A total of 1415 (5.8%)
      participants had at least 1 PVC at baseline, and 591 developed incident ischemic
      stroke during an average (SD) follow-up of 6.0 (2.0) years. In a cox proportional
      hazards model adjusted for age, sex, race, geographic region, education, previous
      heart disease, systolic blood pressure, blood pressure-lowering medications,
      current smoking, diabetes mellitus, left ventricular hypertrophy by ECG, and
      aspirin use and warfarin use, the presence of PVCs was associated with 38%
      increased risk of ischemic stroke (hazard ratio [95% confidence interval], 1.38
      [1.05-1.81]). CONCLUSIONS: PVCs are common on routine screening ECGs and are
      associated with an increased risk of ischemic stroke.

PMID- 25873605
TI  - Microbial community structure and functional diversity of nitrogen-fixing
      bacteria associated with Colophospermum mopane.
AB  - Colophospermum mopane is an indigenous legume tree that grows in Southern Africa
      and is one of the predominant trees of the woodland vegetation. In order to
      increase knowledge about its ecology, especially how C. mopane thrives in the
      nitrogen-poor soils of the region, we analyzed the root-associated bacteria to
      assess the active diazotrophic diversity and total microbial diversity by culture
      dependent and independent techniques. Root nodules were not detected but in some
      samples the lateral roots showed an outgrowth-like protuberance, that were not
      likely to have functions related to legume root nodules. The bacterial isolates
      recovered were related to Actinobacteria, Firmicutes and Proteobacteria. The
      total microbial diversity was dominated by Actinobacteria-related phylotypes,
      while the active diazotrophic diversity showed that the majority of the sequences
      were related to the order Rhizobiales but also to Spirochaetes, Firmicutes,
      Bacteroidetes and Deltaproteobacteria. Several isolates showed characteristics of
      plant growth-promoting bacteria. These findings increase the spectrum of possible
      phylotypes that can be found in legume trees that are typically nodulated by
      Alpha- and Betaproteobacteria, and reveal for the first time a surprising
      diversity of nitrogen-fixing bacteria active in legume tree roots. 

PMID- 25873606
TI  - Monitoring the dynamics of syntrophic beta-oxidizing bacteria during anaerobic
      degradation of oleic acid by quantitative PCR.
AB  - The ecophysiology of long-chain fatty acid-degrading syntrophic beta-oxidizing
      bacteria has been poorly understood due to a lack of quantitative abundance data.
      Here, TaqMan quantitative PCR (qPCR) assays targeting the 16S rRNA gene of the
      known mesophilic syntrophic beta-oxidizing bacterial genera Syntrophomonas and
      Syntrophus were developed and validated. Microbial community dynamics were
      followed using qPCR and Illumina-based high-throughput amplicon sequencing in
      triplicate methanogenic bioreactors subjected to five consecutive batch feedings
      of oleic acid. With repeated oleic acid feeding, the initial specific methane
      production rate significantly increased along with the relative abundances of
      Syntrophomonas and methanogenic archaea in the bioreactor communities. The novel
      qPCR assays showed that Syntrophomonas increased from 7 to 31% of the bacterial
      community 16S rRNA gene concentration, whereas that of Syntrophus decreased from
      0.02 to less than 0.005%. High-throughput amplicon sequencing also revealed that
      Syntrophomonas became the dominant genus within the bioreactor microbiomes. These
      results suggest that increased specific mineralization rates of oleic acid were
      attributed to quantitative shifts within the microbial communities toward higher
      abundances of syntrophic beta-oxidizing bacteria and methanogenic archaea. The
      novel qPCR assays targeting syntrophic beta-oxidizing bacteria may thus serve as
      monitoring tools to indicate the fatty acid beta-oxidization potential of
      anaerobic digester communities. 

PMID- 25873607
TI  - Hospitals partner with SNFs to reduce readmissions.

PMID- 25873608
TI  - Consider standard ACS pharmacotherapies for patients with CKD, experts suggest.

PMID- 25873610
TI  - Timing critical in hypertension treatment, study finds.

PMID- 25873611
TI  - Importance of ethnicity and smoking status in EGFR gene testing in lung cancers.

PMID- 25873612
TI  - Importance of ethnicity and smoking status in EGFR gene testing in lung cancers.

PMID- 25873613
TI  - Discussion of learning assessments in postgraduate teaching and learning
      curricula.

PMID- 25873614
TI  - Discussion of learning assessments in postgraduate teaching and learning
      curricula.

PMID- 25873615
TI  - Medication reconciliation to facilitate transitions of care after
      hospitalization.

PMID- 25873616
TI  - Specialty pharmacy and the medication access dilemma.

PMID- 25873617
TI  - Past and present of antiobesity agents: focus on monoamine modulators.
AB  - PURPOSE: A review of recently approved antiobesity medications, including their
      neuropharmacology, efficacy data from clinical trials, and important patient
      safety considerations, is presented. SUMMARY: Obesity affects roughly 34% of
      Americans and is associated with increased risks of type 2 diabetes,
      hypertension, and coronary artery disease, as well as increased mortality and
      healthcare costs. Most pharmacologic agents used to treat obesity work by
      modulating monoamine neurotransmitters such as serotonin, norepinephrine, and
      dopamine. Since the U.S. market withdrawal of agents such as fenfluramine,
      dexfenfluramine, and sibutramine due to safety concerns, the Food and Drug
      Administration (FDA) has approved three monoamine modulators for long-term
      obesity management: the serotonergic agent lorcaserin (approved by FDA in 2012),
      a combination product containing phentermine and extended-release (ER) topiramate
      (also approved in 2012), and another combination product consisting of ER
      naltrexone and ER bupropion (approved in late 2014). In Phase III trials of the
      three products, mean weight reductions ranging from 4.7 to 10.2 kg over periods
      of one and two years were reported, with substantial percentages of patients
      achieving weight loss of >=5%. Adverse effects reported among clinical trial
      participants were generally mild; however, as the trials excluded patients with
      significant cardiovascular risks (e.g., uncontrolled hypertension, valvular heart
      disease), cautious patient selection and monitoring are advised. CONCLUSION:
      Recently approved medications for long-term management of obesity include
      lorcaserin, phentermine-topiramate, and naltrexone-bupropion. When these drugs
      are used to facilitate weight loss, pharmacists can play an important role in
      helping to ensure appropriate patient selection and monitoring.

PMID- 25873618
TI  - Catheter-directed thrombolysis with alteplase and bivalirudin in a patient with
      heparin-induced thrombocytopenia.
AB  - PURPOSE: The case of a patient with confirmed heparin-induced thrombocytopenia
      (HIT) and anticoagulation failure undergoing catheter-directed thrombolysis (CDT)
      with alteplase and bivalirudin for extensive thrombosis is reported. SUMMARY: A
      48-year-old, morbidly obese Caucasian woman was admitted to a trauma-surgical
      intensive care unit (TSICU) after a motor vehicle accident. The patient suffered
      aortic and renal lacerations, multiple rib and spinal fractures, pleural
      effusion, bilateral subdural hematomas, and cerebral edema. An inferior vena cava
      (IVC) filter was placed on hospital day 3, and prophylactic enoxaparin was
      initiated. The patient was diagnosed with HIT on hospital day 10. Systemic
      bivalirudin was initiated, and the patient was transitioned to therapeutic
      fondaparinux on hospital day 13. The patient continued to improve and was
      transferred from the TSICU to a step-down unit a few days later; the IVC filter
      remained in place. On hospital day 20, the patient developed respiratory distress
      and was transferred back to the TSICU. Computed tomography angiography was
      performed and revealed a questionable pulmonary embolism and distended IVC and
      iliac veins. Lower-extremity Doppler ultrasound revealed extensive thrombosis. On
      hospital day 21, the patient underwent CDT with alteplase and bivalirudin
      infusions through two CDT sheaths for approximately 36 hours, after which most of
      the thrombus had dissipated. The IVC filter and drug administration sheaths were
      removed. After the procedure, the patient received bivalirudin and was later
      transitioned to warfarin. CONCLUSION: A 48-year-old woman with HIT and
      anticoagulation failure possibly due to the presence of an IVC filter was
      successfully treated with CDT using alteplase and bivalirudin.

PMID- 25873619
TI  - The intersection of public policy and professional responsibility.

PMID- 25873620
TI  - National trends in prescription drug expenditures and projections for 2015.
AB  - PURPOSE: An analysis of trends in U.S. pharmaceutical spending is presented,
      including projections for drug expenditures in nonfederal hospital and clinic
      settings in 2015. METHODS: Prescription drug expenditure data through September
      2014 were obtained from the IMS Health National Sales Perspectives database and
      were analyzed descriptively. Other factors that may influence prescription
      spending in hospitals and clinics in 2015, including new drug approvals and
      patent expirations, were analyzed. Expenditure projections were based on a
      combination of quantitative and qualitative analyses and expert opinion. RESULTS:
      Total prescription sales for the 12 months ending September 30, 2014, were $360.7
      billion, 12.2% higher than during the previous 12 months. With $6.6 billion in
      expenditures in the first 9 months of 2014, sofosbuvir topped the overall list of
      drugs based on sales, followed by aripiprazole and insulin glargine.
      Pharmaceutical spending by clinics and nonfederal hospitals rose by 13.3% and
      4.0%, respectively. For the first 9 months of 2014, the top drugs based on
      expenditures were infliximab, pegfilgrastim, and epoetin alfa in clinics and
      infliximab, rituximab, and pegfilgrastim in hospitals. Specialty drugs continued
      to constitute an increasing portion of drug expenditures and will contribute to
      higher expenditures in 2015. CONCLUSION: Growth in U.S. prescription drug
      expenditures is expected to continue to increase in 2015. The projected increases
      in total drug expenditures are 7-9% across all settings, 12-14% in clinics, and 5
      7% in hospitals. Health-system pharmacy leaders should carefully examine their
      own local drug utilization patterns to determine their own organization's
      anticipated spending in 2015.

PMID- 25873621
TI  - Implementation of transitions-of-care services through acute care and outpatient
      pharmacy collaboration.
AB  - PURPOSE: The implementation of a practice model designed to reduce hospital
      readmissions through optimal deployment of pharmacy staff on multidisciplinary
      care collaboration teams is described. SUMMARY: In response to Affordable Care
      Act provisions aimed at reducing preventable hospital readmissions, the pharmacy
      department at The Johns Hopkins Hospital (JHH) led the implementation of a new
      pharmacy services model spanning both inpatient and outpatient settings. Key
      components of the model include (1) increased pharmacist participation in
      multidisciplinary rounds, (2) targeted medication reconciliation and patient
      education, (3) postdischarge phone monitoring of selected patients, and (4)
      bedside discharge medication delivery performed by a "transitions pharmacist
      extender." Incorporation of care coordination activities into the daily workflow
      has increased the rate of patient education on high-risk medications and allowed
      for affordable and effective medication regimens to be designed and prescriptions
      to be filled prior to patient discharge. The ultimate goal is enhanced
      multidisciplinary collaboration to decrease hospital readmissions by increasing
      medication adherence and patients' understanding of medications. CONCLUSION: The
      inpatient and outpatient pharmacy teams at JHH collaborated to improve their
      understanding of patients' medication use prior to admission through targeted
      medication reconciliation, education of patients on high-risk medications
      initiated during admission, and development of affordable and practical
      medication regimens that patients would receive in hand on discharge. A pharmacy
      team model was developed to ensure that these services are adequately provided
      and enhance patient understanding of the importance of medications for acute and
      chronic disease state management.

PMID- 25873622
TI  - Integration of pharmacists into team-based ambulatory care practice models.

PMID- 25873623
TI  - Importance of specialty pharmacy to your health system.

PMID- 25873624
TI  - NMD3 regulates both mRNA and rRNA nuclear export in African trypanosomes via an
      XPOI-linked pathway.
AB  - Trypanosomes mostly regulate gene expression through post-transcriptional
      mechanisms, particularly mRNA stability. However, much mRNA degradation is
      cytoplasmic such that mRNA nuclear export must represent an important level of
      regulation. Ribosomal RNAs must also be exported from the nucleus and the
      trypanosome orthologue of NMD3 has been confirmed to be involved in rRNA
      processing and export, matching its function in other organisms. Surprisingly, we
      found that TbNMD3 depletion also generates mRNA accumulation of procyclin
      associated genes (PAGs), these being co-transcribed by RNA polymerase I with the
      procyclin surface antigen genes expressed on trypanosome insect forms. By whole
      transcriptome RNA-seq analysis of TbNMD3-depleted cells we confirm the regulation
      of the PAG transcripts by TbNMD3 and using reporter constructs reveal that PAG1
      regulation is mediated by its 5'UTR. Dissection of the mechanism of regulation
      demonstrates that it is not dependent upon translational inhibition mediated by
      TbNMD3 depletion nor enhanced transcription. However, depletion of the nuclear
      export factors XPO1 or MEX67 recapitulates the effects of TbNMD3 depletion on PAG
      mRNAs and mRNAs accumulated in the nucleus of TbNMD3-depleted cells. These
      results invoke a novel RNA regulatory mechanism involving the NMD3-dependent
      nuclear export of mRNA cargos, suggesting a shared platform for mRNA and rRNA
      export. 

PMID- 25873625
TI  - Regulation of NEIL1 protein abundance by RAD9 is important for efficient base
      excision repair.
AB  - RAD9 participates in DNA damage-induced cell cycle checkpoints and DNA repair. As
      a member of the RAD9-HUS1-RAD1 (9-1-1) complex, it can sense DNA damage and
      recruit ATR to damage sites. RAD9 binding can enhance activities of members of
      different DNA repair pathways, including NEIL1 DNA glycosylase, which initiates
      base excision repair (BER) by removing damaged DNA bases. Moreover, RAD9 can act
      independently of 9-1-1 as a gene-specific transcription factor. Herein, we show
      that mouse Rad9(-/-) relative to Rad9(+/+) embryonic stem (ES) cells have reduced
      levels of Neil1 protein. Also, human prostate cancer cells, DU145 and PC-3,
      knocked down for RAD9 demonstrate reduced NEIL1 abundance relative to controls.
      We found that Rad9 is required for Neil1 protein stability in mouse ES cells,
      whereas it regulates NEIL1 transcription in the human cells. RAD9 depletion
      enhances sensitivity to UV, gamma rays and menadione, but ectopic expression of
      RAD9 or NEIL1 restores resistance. Glycosylase/apurinic lyase activity was
      reduced in Rad9(-/-) mouse ES and RAD9 knocked-down human prostate cancer whole
      cell extracts, relative to controls. Neil1 or Rad9 addition restored this
      incision activity. Thus, we demonstrate that RAD9 regulates BER by controlling
      NEIL1 protein levels, albeit by different mechanisms in human prostate cancer
      versus mouse ES cells. 

PMID- 25873626
TI  - cMonkey2: Automated, systematic, integrated detection of co-regulated gene
      modules for any organism.
AB  - The cMonkey integrated biclustering algorithm identifies conditionally co
      regulated modules of genes (biclusters). cMonkey integrates various orthogonal
      pieces of information which support evidence of gene co-regulation, and optimizes
      biclusters to be supported simultaneously by one or more of these prior
      constraints. The algorithm served as the cornerstone for constructing the first
      global, predictive Environmental Gene Regulatory Influence Network (EGRIN) model
      for a free-living cell, and has now been applied to many more organisms. However,
      due to its computational inefficiencies, long run-time and complexity of various
      input data types, cMonkey was not readily usable by the wider community. To
      address these primary concerns, we have significantly updated the cMonkey
      algorithm and refactored its implementation, improving its usability and
      extendibility. These improvements provide a fully functioning and user-friendly
      platform for building co-regulated gene modules and the tools necessary for their
      exploration and interpretation. We show, via three separate analyses of data for
      E. coli, M. tuberculosis and H. sapiens, that the updated algorithm and inclusion
      of novel scoring functions for new data types (e.g. ChIP-seq and transcription
      factor over-expression [TFOE]) improve discovery of biologically informative co
      regulated modules. The complete cMonkey2 software package, including source code,
      is available at https://github.com/baliga-lab/cmonkey2. 

PMID- 25873628
TI  - PLIP: fully automated protein-ligand interaction profiler.
AB  - The characterization of interactions in protein-ligand complexes is essential for
      research in structural bioinformatics, drug discovery and biology. However,
      comprehensive tools are not freely available to the research community. Here, we
      present the protein-ligand interaction profiler (PLIP), a novel web service for
      fully automated detection and visualization of relevant non-covalent protein
      ligand contacts in 3D structures, freely available at projects.biotec.tu
      dresden.de/plip-web. The input is either a Protein Data Bank structure, a protein
      or ligand name, or a custom protein-ligand complex (e.g. from docking). In
      contrast to other tools, the rule-based PLIP algorithm does not require any
      structure preparation. It returns a list of detected interactions on single atom
      level, covering seven interaction types (hydrogen bonds, hydrophobic contacts, pi
      stacking, pi-cation interactions, salt bridges, water bridges and halogen bonds).
      PLIP stands out by offering publication-ready images, PyMOL session files to
      generate custom images and parsable result files to facilitate successive data
      processing. The full python source code is available for download on the website.
      PLIP's command-line mode allows for high-throughput interaction profiling. 

PMID- 25873627
TI  - Assessing the translational landscape of myogenic differentiation by ribosome
      profiling.
AB  - The formation of skeletal muscles is associated with drastic changes in protein
      requirements known to be safeguarded by tight control of gene transcription and
      mRNA processing. The contribution of regulation of mRNA translation during
      myogenesis has not been studied so far. We monitored translation during myogenic
      differentiation of C2C12 myoblasts, using a simplified protocol for ribosome
      footprint profiling. Comparison of ribosome footprints to total RNA showed that
      gene expression is mostly regulated at the transcriptional level. However, a
      subset of transcripts, enriched for mRNAs encoding for ribosomal proteins, was
      regulated at the level of translation. Enrichment was also found for specific
      pathways known to regulate muscle biology. We developed a dedicated pipeline to
      identify translation initiation sites (TISs) and discovered 5333 unannotated
      TISs, providing a catalog of upstream and alternative open reading frames used
      during myogenesis. We identified 298 transcripts with a significant switch in TIS
      usage during myogenesis, which was not explained by alternative promoter usage,
      as profiled by DeepCAGE. Also these transcripts were enriched for ribosomal
      protein genes. This study demonstrates that differential mRNA translation
      controls protein expression of specific subsets of genes during myogenesis.
      Experimental protocols, analytical workflows, tools and data are available
      through public repositories (http://lumc.github.io/ribosome-profiling-analysis
      framework/). 

PMID- 25873630
TI  - Coronary heart disease prediction: Apolipoprotein B shows its might again--but
      still in vain?

PMID- 25873629
TI  - Microfluidic droplet enrichment for targeted sequencing.
AB  - Targeted sequence enrichment enables better identification of genetic variation
      by providing increased sequencing coverage for genomic regions of interest. Here,
      we report the development of a new target enrichment technology that is highly
      differentiated from other approaches currently in use. Our method, MESA
      (Microfluidic droplet Enrichment for Sequence Analysis), isolates genomic DNA
      fragments in microfluidic droplets and performs TaqMan PCR reactions to identify
      droplets containing a desired target sequence. The TaqMan positive droplets are
      subsequently recovered via dielectrophoretic sorting, and the TaqMan amplicons
      are removed enzymatically prior to sequencing. We demonstrated the utility of
      this approach by generating an average 31.6-fold sequence enrichment across 250
      kb of targeted genomic DNA from five unique genomic loci. Significantly, this
      enrichment enabled a more comprehensive identification of genetic polymorphisms
      within the targeted loci. MESA requires low amounts of input DNA, minimal prior
      locus sequence information and enriches the target region without PCR bias or
      artifacts. These features make it well suited for the study of genetic variation
      in a number of research and diagnostic applications. 

PMID- 25873631
TI  - Ancestral Relationships Using Metafounders: Finite Ancestral Populations and
      Across Population Relationships.
AB  - Recent use of genomic (marker-based) relationships shows that relationships exist
      within and across base population (breeds or lines). However, current treatment
      of pedigree relationships is unable to consider relationships within or across
      base populations, although such relationships must exist due to finite size of
      the ancestral population and connections between populations. This complicates
      the conciliation of both approaches and, in particular, combining pedigree with
      genomic relationships. We present a coherent theoretical framework to consider
      base population in pedigree relationships. We suggest a conceptual framework that
      considers each ancestral population as a finite-sized pool of gametes. This
      generates across-individual relationships and contrasts with the classical view
      which each population is considered as an infinite, unrelated pool. Several
      ancestral populations may be connected and therefore related. Each ancestral
      population can be represented as a "metafounder," a pseudo-individual included as
      founder of the pedigree and similar to an "unknown parent group." Metafounders
      have self- and across relationships according to a set of parameters, which
      measure ancestral relationships, i.e., homozygozities within populations and
      relationships across populations. These parameters can be estimated from existing
      pedigree and marker genotypes using maximum likelihood or a method based on
      summary statistics, for arbitrarily complex pedigrees. Equivalences of genetic
      variance and variance components between the classical and this new
      parameterization are shown. Segregation variance on crosses of populations is
      modeled. Efficient algorithms for computation of relationship matrices, their
      inverses, and inbreeding coefficients are presented. Use of metafounders leads to
      compatibility of genomic and pedigree relationship matrices and to simple
      computing algorithms. Examples and code are given. 

PMID- 25873632
TI  - Cortical Folding of the Primate Brain: An Interdisciplinary Examination of the
      Genetic Architecture, Modularity, and Evolvability of a Significant Neurological
      Trait in Pedigreed Baboons (Genus Papio).
AB  - Folding of the primate brain cortex allows for improved neural processing power
      by increasing cortical surface area for the allocation of neurons. The
      arrangement of folds (sulci) and ridges (gyri) across the cerebral cortex is
      thought to reflect the underlying neural network. Gyrification, an adaptive trait
      with a unique evolutionary history, is affected by genetic factors different from
      those affecting brain volume. Using a large pedigreed population of ~1000 Papio
      baboons, we address critical questions about the genetic architecture of primate
      brain folding, the interplay between genetics, brain anatomy, development,
      patterns of cortical-cortical connectivity, and gyrification's potential for
      future evolution. Through Mantel testing and cluster analyses, we find that the
      baboon cortex is quite evolvable, with high integration between the genotype and
      phenotype. We further find significantly similar partitioning of variation
      between cortical development, anatomy, and connectivity, supporting the
      predictions of tension-based models for sulcal development. We identify a
      significant, moderate degree of genetic control over variation in sulcal length,
      with gyrus-shape features being more susceptible to environmental effects.
      Finally, through QTL mapping, we identify novel chromosomal regions affecting
      variation in brain folding. The most significant QTL contain compelling candidate
      genes, including gene clusters associated with Williams and Down syndromes. The
      QTL distribution suggests a complex genetic architecture for gyrification with
      both polygeny and pleiotropy. Our results provide a solid preliminary
      characterization of the genetic basis of primate brain folding, a unique and
      biomedically relevant phenotype with significant implications in primate brain
      evolution. 

PMID- 25873633
TI  - Transition Densities and Sample Frequency Spectra of Diffusion Processes with
      Selection and Variable Population Size.
AB  - Advances in empirical population genetics have made apparent the need for models
      that simultaneously account for selection and demography. To address this need,
      we here study the Wright-Fisher diffusion under selection and variable effective
      population size. In the case of genic selection and piecewise-constant effective
      population sizes, we obtain the transition density by extending a recently
      developed method for computing an accurate spectral representation for a constant
      population size. Utilizing this extension, we show how to compute the sample
      frequency spectrum in the presence of genic selection and an arbitrary number of
      instantaneous changes in the effective population size. We also develop an
      alternate, efficient algorithm for computing the sample frequency spectrum using
      a moment-based approach. We apply these methods to answer the following
      questions: If neutrality is incorrectly assumed when there is selection, what
      effects does it have on demographic parameter estimation? Can the impact of
      negative selection be observed in populations that undergo strong exponential
      growth? 

PMID- 25873634
TI  - Full dose, reduced dose or discontinuation of etanercept in rheumatoid arthritis.
AB  - BACKGROUND: The aim of the Dose Reduction or Discontinuation of Etanercept in
      Methotrexate-Treated Rheumatoid Arthritis Patients Who Have Achieved a Stable Low
      Disease Activity-State study was to investigate the effect of etanercept (ETN)
      dose maintenance, reduction or withdrawal on patients with rheumatoid arthritis
      (RA) who had already achieved stable low disease activity (LDA) on ETN 50
      mg+methotrexate (MTX). METHODS: Patients with RA (n=91) and stable LDA with ETN
      50 mg once weekly (QW)+MTX were included. After 8 weeks with unchanged treatment,
      73 patients were randomised in a double-blind design to ETN 50 mg QW+MTX (ETN50),
      ETN 25 mg QW+MTX (ETN25) or placebo QW+MTX (PBO) for 48 weeks. Patients who
      flared were declared failures and treated with open-label ETN50 until week 48.
      The primary outcome was the proportion of patients on ETN50 versus PBO who were
      non-failures after 48 weeks. RESULTS: The proportion of non-failure patients was
      significantly lower with ETN50 (52%; p=0.007) and ETN25 (44%; p=0.044) versus PBO
      (13%). Median time to failure was significantly shorter with PBO (6 weeks)
      compared with ETN50 (48 weeks; p=0.001) and ETN25 (36 weeks; p<0.001). The
      majority of patients who flared regained LDA with open-label ETN50 quickly.
      Adverse events were consistent with the known side effect profiles of these
      medications. CONCLUSIONS: In patients with established RA who have achieved
      stable LDA on ETN50+MTX, continuing both is superior to PBO+MTX. Reduced dose ETN
      was also more effective than PBO in maintaining a favourable response, suggesting
      that a maintenance strategy with reduced dose ETN may be possible in a number of
      patients with established RA. TRIAL REGISTRATION NUMBER: NCT00858780.

PMID- 25873635
TI  - Efficacy and safety of tabalumab, an anti-B-cell-activating factor monoclonal
      antibody, in patients with rheumatoid arthritis who had an inadequate response to
      methotrexate therapy: results from a phase III multicentre, randomised, double
      blind study.
AB  - OBJECTIVES: Randomised, double-blind, placebo-controlled study to evaluate
      efficacy and safety of tabalumab in patients with rheumatoid arthritis (RA) with
      inadequate responses to methotrexate (MTX-IR). METHODS: 1041 patients with
      moderate-severe RA despite ongoing MTX enrolled in a 52-week study evaluating
      subcutaneous tabalumab 120 mg every four weeks (120/Q4W) or 90 mg every two weeks
      (90/Q2W) versus placebo. Primary endpoints were American College of Rheumatology
      20% (ACR20) response rate and Health Assessment Questionnaire-Disability Index
      change from baseline at 24 weeks and modified Total Sharp Score (mTSS) change at
      52 weeks. RESULTS: There were no significant differences in ACR20 responses at
      week 24 or mTSS change from baseline at week 52 among treatment groups. Declines
      were seen in CD20+ B cells and immunoglobulin levels in tabalumab groups, but not
      placebo: B cells (-15.0%, -18.8%, 5.3%, in the 120/Q4W, 90/Q2W, and placebo
      groups, respectively); IgM (-16.3%, -19.4%, -0.1%), IgA (-11.4%, -4.7%, 1.2%) and
      IgG (-8.6%, -7.8%, 0.1%). Discontinuations due to adverse events were similar
      between groups. Numerically more serious infections were reported in tabalumab
      groups (1.7%, 0.6%, 0.3%); numerically more injection-site reactions were
      reported in the 90/Q2W group (2.3%, 4.3%, 2.3%). CONCLUSIONS: Neither clinical
      efficacy nor significant safety signals were observed with tabalumab despite
      evidence of biological activity. This study was terminated early due to
      insufficient efficacy. TRIAL REGISTRATION NUMBER: NCT01198002.

PMID- 25873636
TI  - Caenorhabditis elegans TBX-2 Directly Regulates Its Own Expression in a Negative
      Autoregulatory Loop.
AB  - T-box genes often exhibit dynamic expression patterns, and their expression
      levels can be crucial for normal function. Despite the importance of these genes,
      there is little known about T-box gene regulation. We have focused on the
      Caenorhabditis elegans gene tbx-2 to understand how T-box gene expression is
      regulated, and here we demonstrate TBX-2 itself directly represses its own
      expression in a negative autoregulatory loop. tbx-2 is essential for normal
      pharyngeal muscle development, and a tbx-2 promoter gfp fusion (Ptbx-2::gfp) is
      transiently expressed in the pharynx during embryogenesis and in a small number
      of head neurons in larvae and adults. Reduced tbx-2 function resulted in ectopic
      Ptbx-2::gfp expression in the seam cells and gut in larvae and adults. Mutation
      of potential T-box binding sites within the tbx-2 promoter resulted in a similar
      pattern of ectopic Ptbx-2::gfp expression, and chromatin immunoprecipitation
      analyses show TBX-2 binds these sites in vivo. This pattern of ectopic Ptbx
      2::gfp expression in tbx-2 mutants was very similar to that observed in mutants
      affecting the NF-Y complex, and our results comparing tbx-2 and nfyb-1 single-
      and double mutants suggest TBX-2 and NF-Y function in a single pathway to repress
      the tbx-2 promoter. The tbx-2 promoter is the first direct target identified for
      TBX-2, and we used it to ask whether SUMOylation is essential for TBX-2
      repression. RNAi knockdown of SUMOylation pathway components led to ectopic Ptbx
      2::gfp expression in the seam cells and gut. Ectopic Ptbx-2::gfp also was
      observed in the syncytial hypodermis, suggesting either the tbx-2 promoter is
      repressed by other SUMOylation dependent mechanisms, or that decreased
      SUMOylation leads to stable changes in seam cell nuclei as they fuse with the
      syncytial hypodermis. We suggest negative autoregulation is an important
      mechanism that allows precise control of tbx-2 expression levels and may allow
      rapid changes in gene expression during development. 

PMID- 25873637
TI  - The Mosaic Mutants of Cucumber: A Method to Produce Knock-Downs of Mitochondrial
      Transcripts.
AB  - Cytoplasmic effects on plant performance are well-documented and result from the
      intimate interaction between organellar and nuclear gene products. In plants,
      deletions, mutations, or chimerism of mitochondrial genes are often associated
      with deleterious phenotypes, as well as economically important traits such as
      cytoplasmic male sterility used to produce hybrid seed. Presently, genetic
      analyses of mitochondrial function and nuclear interactions are limited because
      there is no method to efficiently produce mitochondrial mutants. Cucumber
      (Cucumis sativus L.) possesses unique attributes useful for organellar genetics,
      including differential transmission of the three plant genomes (maternal for
      plastid, paternal for mitochondrial, and bi-parental for nuclear), a relatively
      large mitochondrial DNA in which recombination among repetitive motifs produces
      rearrangements, and the existence of strongly mosaic (MSC) paternally transmitted
      phenotypes that appear after passage of wild-type plants through cell cultures
      and possess unique rearrangements in the mitochondrial DNA. We sequenced the
      mitochondrial DNA from three independently produced MSC lines and revealed under
      represented regions and reduced transcription of mitochondrial genes carried in
      these regions relative to the wild-type parental line. Mass spectrometry and
      Western blots did not corroborate transcriptional differences in the
      mitochondrial proteome of the MSC mutant lines, indicating that post
      transcriptional events, such as protein longevity, may compensate for reduced
      transcription in MSC mitochondria. Our results support cucumber as a model system
      to produce transcriptional "knock-downs" of mitochondrial genes useful to study
      mitochondrial responses and nuclear interactions important for plant performance.

PMID- 25873640
TI  - Reliability and agreement studies: a guide for clinical investigators.

PMID- 25873639
TI  - Screening diabetic patients for non-alcoholic fatty liver disease with controlled
      attenuation parameter and liver stiffness measurements: a prospective cohort
      study.
AB  - OBJECTIVE: Type 2 diabetes is an important risk factor for non-alcoholic fatty
      liver disease (NAFLD), but current guidelines provide conflicting recommendations
      on whether diabetic patients should be screened for NAFLD. We therefore studied
      the strategy of screening diabetic patients by FibroScan. DESIGN: Liver fat and
      fibrosis were assessed by controlled attenuation parameter (CAP) and liver
      stiffness measurements (LSM) by FibroScan at a diabetic centre for patients from
      primary care and hospital clinics. Probe-specific LSM cut-offs were used to
      detect advanced fibrosis. RESULTS: Of 1918 patients examined, 1799 (93.8%) had
      valid CAP and 1884 (98.2%) had reliable LSM (1770 with the M probe and 114 with
      the XL probe). The proportion of patients with increased CAP and LSM was 72.8%
      (95% CI 70.7% to 74.8%) and 17.7% (95% CI 16.0% to 19.5%), respectively. By
      multivariable analysis, female gender, higher body mass index, triglycerides,
      fasting plasma glucose and alanine aminotransferase (ALT) and non-insulin use
      were associated with increased CAP. Longer duration of diabetes, higher body mass
      index, increased ALT and spot urine albumin:creatinine ratio and lower high
      density lipoprotein-cholesterol were associated with increased LSM. Ninety-four
      patients (80% had increased LSM) underwent liver biopsy: 56% had steatohepatitis
      and 50% had F3-4 disease. CONCLUSIONS: Diabetic patients have a high prevalence
      of NAFLD and advanced fibrosis. Those with obesity and dyslipidaemia are at
      particularly high risk and may be the target for liver assessment. Our data
      support screening for NAFLD and/or advanced fibrosis in patients with type 2
      diabetes.

PMID- 25873641
TI  - Efficacy of mesalazine in IBS.

PMID- 25873638
TI  - Functional Analysis of Developmentally Regulated Genes chs7 and sec22 in the
      Ascomycete Sordaria macrospora.
AB  - During sexual development, filamentous ascomycetes form complex, three
      dimensional fruiting bodies for the generation and dispersal of spores. In
      previous studies, we identified genes with evolutionary conserved expression
      patterns during fruiting body formation in several fungal species. Here, we
      present the functional analysis of two developmentally up-regulated genes, chs7
      and sec22, in the ascomycete Sordaria macrospora. The genes encode a class VII
      (division III) chitin synthase and a soluble N-ethylmaleimide-sensitive-factor
      attachment protein receptor (SNARE) protein, respectively. Deletion mutants of
      chs7 had normal vegetative growth and were fully fertile but showed sensitivity
      toward cell wall stress. Deletion of sec22 resulted in a reduced number of
      ascospores and in defects in ascospore pigmentation and germination, whereas
      vegetative growth was normal in the mutant. A SEC22-EGFP fusion construct under
      control of the native sec22 promoter and terminator regions was expressed during
      different stages of sexual development. Expression of several development-related
      genes was deregulated in the sec22 mutant, including three genes involved in
      melanin biosynthesis. Our data indicate that chs7 is dispensable for fruiting
      body formation in S. macrospora, whereas sec22 is required for ascospore
      maturation and germination and thus involved in late stages of sexual
      development. 

PMID- 25873646
TI  - An intervention to reduce the number of convenience stores selling tobacco:
      feasibility study.
AB  - BACKGROUND: Reduction of the availability of tobacco has been proposed as a means
      of reducing and denormalising tobacco use. Some retailers have stopped selling
      tobacco. Therefore, we investigated how willing New Zealand convenience store
      owners were to stop selling tobacco or sell nicotine replacement therapy.
      Promotion of their stores was offered as an incentive to stop selling tobacco.
      METHODS: We asked convenience store owners in the Auckland metropolitan region of
      New Zealand to choose one of three actions. The first was to stop selling tobacco
      for a short period of time; the second was to restrict the hours that they sold
      tobacco; the third was to display and sell nicotine replacement therapy. All
      participating retailers completed a short interview about selling tobacco. We
      also surveyed customers about nicotine replacement and cessation. RESULTS: One
      third of eligible retailers agreed to participate. Most who participated (93%)
      were unwilling to stop or restrict tobacco sales and 2 (7%) had already stopped
      selling tobacco. Tobacco was perceived as a key product for their businesses.
      Very few customers who purchased cigarettes noticed nicotine replacement therapy
      or obtained it from convenience stores. CONCLUSIONS: Substantially reducing the
      availability of tobacco in communities is likely to require legislative
      approaches, underpinned by sustained community pressure and support for
      convenience store owners who are willing to change their business model.

PMID- 25873647
TI  - Educational differences in the impact of pictorial cigarette warning labels on
      smokers: findings from the International Tobacco Control (ITC) Europe surveys.
AB  - OBJECTIVE: To examine (1) the impact of pictorial cigarette warning labels on
      changes in self-reported warning label responses: warning salience, cognitive
      responses, forgoing cigarettes and avoiding warnings, and (2) whether these
      changes differed by smokers' educational level. METHODS: Longitudinal data of
      smokers from two survey waves of the International Tobacco Control (ITC) Europe
      Surveys were used. In France and the UK, pictorial warning labels were
      implemented on the back of cigarette packages between the two survey waves. In
      Germany and the Netherlands, the text warning labels did not change. FINDINGS:
      Warning salience decreased between the surveys in France (OR=0.81, p=0.046) and
      showed a non-significant increase in the UK (OR=1.30, p=0.058), cognitive
      responses increased in the UK (OR=1.34, p<0.001) and decreased in France
      (OR=0.70, p=0.002), forgoing cigarettes increased in the UK (OR=1.65, p<0.001)
      and decreased in France (OR=0.83, p=0.047), and avoiding warnings increased in
      France (OR=2.93, p<0.001) and the UK (OR=2.19, p<0.001). Warning salience and
      cognitive responses decreased in Germany and the Netherlands, forgoing did not
      change in these countries and avoidance increased in Germany. In general, these
      changes in warning label responses did not differ by education. However, in the
      UK, avoidance increased especially among low (OR=2.25, p=0.001) and moderate
      educated smokers (OR=3.21, p<0.001). CONCLUSIONS: The warning labels implemented
      in France in 2010 and in the UK in 2008 with pictures on one side of the
      cigarette package did not succeed in increasing warning salience, but did
      increase avoidance. The labels did not increase educational inequalities among
      continuing smokers.

PMID- 25873648
TI  - Comparison of high-risk histopathological features in eyes with primary or
      secondary enucleation for retinoblastoma.
AB  - AIMS: To compare high-risk histopathology of eyes with primary versus secondary
      enucleation from patients with retinoblastoma. PATIENTS AND METHODS: A
      retrospective histopathology review identified 207 eyes enucleated from 202
      patients between March 1997 and August 2013. Our review considered high-risk
      histopathological features to include extraocular disease or invasion of the
      anterior chamber, iris, ciliary body, choroid (massive), postlaminar optic nerve
      or sclera. RESULTS: Most eyes (144, 70%) were primarily enucleated; 63 (30%) were
      secondarily enucleated after neoadjuvant therapy. The primary enucleation group
      had more advanced disease (Reese-Ellsworth group V: 95% vs 59%; International
      Classification Group D/E: 97% vs 59%; p<0.001). The incidence of high-risk
      histopathology features was similar between groups (32% vs 21%, n=59; p=0.132).
      The type of prior therapy was not associated with high-risk histopathology
      features. Time to enucleation was longer for secondarily enucleated eyes with
      high-risk features. Choroid and postlaminar optic nerve invasion were more
      frequent in eyes primarily enucleated (p<0.001). Forty-six of the 59 (78%)
      patients with high-risk features received adjuvant chemotherapy and/or external
      beam radiation therapy. Three patients who received primary enucleation and
      adjuvant therapy died of metastatic recurrence. CONCLUSIONS: Despite the more
      favourable classification of eyes treated with neoadjuvant therapy, the risk of
      high-risk histopathology features at enucleation was comparable with eyes
      undergoing primary enucleation. Delayed enucleation was associated with these
      features, and the majority of patients required further adjuvant therapy. Caution
      must be exercised in treating recalcitrant intraocular retinoblastoma to promptly
      pursue definitive enucleation in an effort to minimise further treatment
      exposures and metastases.

PMID- 25873649
TI  - The survival of an angled extended Jones' tube.
AB  - AIM: To analyse the long-term outcome of lacrimal bypass surgery with an angled
      extended Jones' tube. DESIGN: Retrospective, non-comparative, non-interventional
      case series. METHODS: Seventy-one patients who underwent transcaruncular
      insertion of an angled extended Jones' tube between 1995 and 2005 were followed
      up over a median period of 8.7 years (range 11 days-17 years). MAIN OUTCOME
      MEASURES: Patency and anatomic position of the tube, type and time lapse of the
      complications and subjective relief of epiphora. RESULTS: Overall, complications
      occurred in 39% of the tubes (35/90) at a median of 25 days (range 3 days-6
      years) after the insertion. The major complications, that is, tube displacement
      or obstruction, were observed in 31% (28/90), with an incidence rate of 8% per
      year. The minor complications, that is, conjunctival overgrowth or granuloma at
      the lateral end, were encountered in 8% (seven of 90). The 10-year tube survival
      rate was 60%, with complete relief of epiphora in 88% of the patients.
      CONCLUSIONS: The long-term outcome with the angled extended Jones' tube inserted
      transcaruncularly remains relatively good, with most of the complications
      occurring in the early postoperative period.

PMID- 25873650
TI  - Visual outcomes in eyes with a distance-dominant diffractive multifocal
      intraocular lens with low near addition power.
AB  - AIM: To compare monocular and binocular visual function between eyes with a
      distance-dominant diffractive multifocal intraocular lens (IOL) with low addition
      power (+2.5 dioptres (D)) and eyes with a monofocal IOL. METHODS: Sixty-four eyes
      of 32 patients undergoing implantation of a diffractive multifocal IOL (Alcon
      ReSTOR +2.5 D, SN6AD2) with a +2.5 D addition and 64 eyes of 32 age-matched
      patients undergoing implantation of a monofocal IOL (SN60WF) were recruited. At 3
      months postoperatively, visual acuity (VA) from far to near distances, contrast
      VA and that with glare (glare VA), glare disability and glare and halo symptoms
      were evaluated. RESULTS: For monocular and binocular VA, mean uncorrected and
      distance-corrected near VA at 0.3 m and intermediate VA at 0.5 m were
      significantly better in the multifocal group than in the monofocal group (p <=
      0.0412). VA at other distances did not differ significantly between groups.
      Photopic and mesopic contrast VA and glare VA and glare disability were similar
      between groups. The percentage of patients who reported glare symptoms did not
      differ significantly between groups, while the percentage of patients who
      reported halo symptoms was greater in the multifocal group (p = 0.0009).
      CONCLUSIONS: A distance-dominant diffractive multifocal IOL with +2.5 D near
      addition provided useful VA at far and intermediate distances. Contrast
      sensitivity with and without glare and glare symptom with this multifocal IOL
      were comparable between the multifocal and monofocal IOLs, although halo symptoms
      were more prominent with the multifocal IOL.

PMID- 25873651
TI  - Eight-flap anastomosis in external dacryocystorhinostomy.
AB  - AIMS: To examine the surgical outcome of external dacryocystorhinostomy (DCR)
      with eight-flap anastomosis (8-flap ex-DCR). METHODS: A retrospective chart
      review was performed for 55 sides of 51 patients with nasolacrimal duct
      obstruction who underwent 8-flap ex-DCR. The patients were followed up
      postoperatively at 1, 2, 4, 8 and 12 weeks, and evaluations were continued with
      12-week follow-ups until postoperative 12 months. Anatomical success was defined
      as no reflux on lacrimal irrigation at 12 months. Functional success was defined
      as no epiphora at postoperative 12 months. The presence of epistaxis and
      postoperative surgical site infections were checked in all patients. The presence
      of granulation tissue around the ostium, under nasal endoscopy, was also examined
      on 14 sides of 14 patients, at each visit. RESULTS: Anatomical success was
      demonstrated on all sides, and functional success was obtained from 54 sides
      (98.2%) of 50 patients. One patient experienced postoperative intermittent
      epiphora on one side. The patients did not show granulation tissue, epistaxis or
      surgical site infection throughout the observation period. CONCLUSIONS: The 8
      flap ex-DCR showed complete anatomical success and favourable functional success
      with no postoperative complications.

PMID- 25873652
TI  - No association between Bach2 gene polymorphisms with Vogt-Koyanagi-Harada
      syndrome (VKH) and Behcet's disease (BD) in a Chinese Han population.
AB  - BACKGROUND: Bach2 was reported to play a key role in T lymphocyte development and
      maturation to mediate immunological homeostasis. Several autoimmune and immune
      related diseases were shown to be associated with Bach2 gene polymorphisms. The
      current study was designed to explore the association between Bach2 gene
      polymorphism with Vogt-Koyanagi-Harada (VKH) syndrome and Behcet's disease (BD)
      in a Chinese Han population. METHODS: -427 patients with BD, 422 patients with
      VKH and 623 controls were recruited for the first stage from a Chinese Han
      population. The second stage included another set of 388 patients with BD and 460
      healthy subjects. PCR fragment length polymorphism methodology was used for
      genotyping. Frequencies of genotypes and alleles were measured by direct counting
      and compared between cases and controls by chi(2) test. RESULTS: No difference
      could be detected between patients suffering from BD or VKH with healthy controls
      concerning allele and genotype frequencies of rs11755527, rs3757247, rs12212193
      and rs2474619. Although in the first stage the frequencies of genotype CC and AC
      of rs2474619 showed a weak statistical difference between BD and the control
      group (Pc=0.02), the difference was lost after the second stage and combined
      stage experiment. CONCLUSIONS: The investigated Bach2 gene polymorphisms
      (rs11755527, rs3757247, rs12212193 and rs2474619) are not related to the
      susceptibility to either VKH or BD in our investigated Chinese Han population.
      CLINICAL TRIAL REGISTRY: This project was registered in the Chinese Clinical
      Trial Registry (registration number: ChiCTR-CCC-12002184).

PMID- 25873653
TI  - The dominant negative ARM domain uncovers multiple functions of PUB13 in
      Arabidopsis immunity, flowering, and senescence.
AB  - Regulating the intensity and duration of immune responses is crucial to combat
      infections without deleterious side effects. Arabidopsis FLS2, the receptor for
      bacterial flagellin, activates immune signalling by association with its partner
      BAK1. Upon flagellin (flg22) perception, the plant U-box E3 ubiquitin ligases
      PUB12 and PUB13 complex with FLS2 in a BAK1-dependent manner, and ubiquitinate
      FLS2 for protein degradation, thereby down-regulating flagellin signalling.
      Domain deletion analysis indicates that the ARM domain of PUB13 interacts with
      the FLS2-BAK1 complex and is phosphorylated by BAK1. Overexpression of the PUB13
      ARM domain alone inhibits flg22-induced FLS2-PUB13 association and PUB12/13
      mediated FLS2 ubiquitination and degradation in Arabidopsis, suggesting that
      ectopic expression of the ARM domain in planta generates a dominant negative
      effect via blocking the ubiquitination activity. Similar to the pub12pub13 double
      mutant, transgenic plants expressing the PUB13 ARM domain display enhanced immune
      responses compared with wild-type plants. Moreover, PUB13ARM transgenic plants
      and the pub12pub13 mutant are more sensitive to stress-induced leaf senescence
      accompanied by elevated expression of stress-induced senescence marker genes. The
      resemblance between PUB13ARM transgenic plants and the pub12pub13 mutant provides
      genetic evidence that ectopic expression of the PUB ARM domain serves as an
      alternative approach to dissect the overlapping functions of closely related PUB
      genes. 

PMID- 25873654
TI  - Understanding developmental and adaptive cues in pine through metabolite
      profiling and co-expression network analysis.
AB  - Conifers include long-lived evergreen trees of great economic and ecological
      importance, including pines and spruces. During their long lives conifers must
      respond to seasonal environmental changes, adapt to unpredictable environmental
      stresses, and co-ordinate their adaptive adjustments with internal developmental
      programmes. To gain insights into these responses, we examined metabolite and
      transcriptomic profiles of needles from naturally growing 25-year-old maritime
      pine (Pinus pinaster L. Aiton) trees over a year. The effect of environmental
      parameters such as temperature and rain on needle development were studied. Our
      results show that seasonal changes in the metabolite profiles were mainly
      affected by the needles' age and acclimation for winter, but changes in
      transcript profiles were mainly dependent on climatic factors. The relative
      abundance of most transcripts correlated well with temperature, particularly for
      genes involved in photosynthesis or winter acclimation. Gene network analysis
      revealed relationships between 14 co-expressed gene modules and development and
      adaptation to environmental stimuli. Novel Myb transcription factors were
      identified as candidate regulators during needle development. Our systems-based
      analysis provides integrated data of the seasonal regulation of maritime pine
      growth, opening new perspectives for understanding the complex regulatory
      mechanisms underlying conifers' adaptive responses. Taken together, our results
      suggest that the environment regulates the transcriptome for fine tuning of the
      metabolome during development. 

PMID- 25873655
TI  - Metabolomic profiling in tomato reveals diel compositional changes in fruit
      affected by source-sink relationships.
AB  - A detailed study of the diurnal compositional changes was performed in tomato
      (Solanum lycopersicum cv. Moneymaker) leaves and fruits. Plants were cultivated
      in a commercial greenhouse under two growth conditions: control and shaded.
      Expanding fruits and the closest mature leaves were harvested during two
      different day/night cycles (cloudy or sunny day). High-throughput robotized
      biochemical phenotyping of major compounds, as well as proton nuclear magnetic
      resonance and mass spectrometry metabolomic profiling, were used to measure the
      contents of about 70 metabolites in the leaves and 60 metabolites in the fruits,
      in parallel with ecophysiological measurements. Metabolite data were processed
      using multivariate, univariate, or clustering analyses and correlation networks.
      The shaded carbon-limited plants adjusted their leaf area, decreased their sink
      carbon demand and showed subtle compositional modifications. For source leaves,
      several metabolites varied along a diel cycle, including those directly linked to
      photosynthesis and photorespiration. These metabolites peaked at midday in both
      conditions and diel cycles as expected. However, transitory carbon storage was
      limited in tomato leaves. In fruits, fewer metabolites showed diel fluctuations,
      which were also of lower amplitude. Several organic acids were among the
      fluctuating metabolites. Diel patterns observed in leaves and especially in
      fruits differed between the cloudy and sunny days, and between the two
      conditions. Relationships between compositional changes in leaves and fruits are
      in agreement with the fact that several metabolic processes of the fruit appeared
      linked to its momentary supply of sucrose. 

PMID- 25873656
TI  - Post-head-emergence frost in wheat and barley: defining the problem, assessing
      the damage, and identifying resistance.
AB  - Radiant frost is a significant production constraint to wheat (Triticum aestivum)
      and barley (Hordeum vulgare), particularly in regions where spring-habit cereals
      are grown through winter, maturing in spring. However, damage to winter-habit
      cereals in reproductive stages is also reported. Crops are particularly
      susceptible to frost once awns or spikes emerge from the protection of the flag
      leaf sheath. Post-head-emergence frost (PHEF) is a problem distinct from other
      cold-mediated production constraints. To date, useful increased PHEF resistance
      in cereals has not been identified. Given the renewed interest in reproductive
      frost damage in cereals, it is timely to review the problem. Here we update the
      extent and impacts of PHEF and document current management options to combat this
      challenge. We clarify terminology useful for discussing PHEF in relation to
      chilling and other freezing stresses. We discuss problems characterizing radiant
      frost, the environmental conditions leading to PHEF damage, and the effects of
      frost at different growth stages. PHEF resistant cultivars would be highly
      desirable, to both reduce the incidence of direct frost damage and to allow the
      timing of crop maturity to be managed to maximize yield potential. A framework of
      potential adaptation mechanisms is outlined. Clarification of these critical
      issues will sharpen research focus, improving opportunities to identify genetic
      sources for improved PHEF resistance. 

PMID- 25873657
TI  - The thioredoxin/peroxiredoxin/sulfiredoxin system: current overview on its redox
      function in plants and regulation by reactive oxygen and nitrogen species.
AB  - In plants, the presence of thioredoxin (Trx), peroxiredoxin (Prx), and
      sulfiredoxin (Srx) has been reported as a component of a redox system involved in
      the control of dithiol-disulfide exchanges of target proteins, which modulate
      redox signalling during development and stress adaptation. Plant thiols, and
      specifically redox state and regulation of thiol groups of cysteinyl residues in
      proteins and transcription factors, are emerging as key components in the plant
      response to almost all stress conditions. They function in both redox sensing and
      signal transduction pathways. Scarce information exists on the transcriptional
      regulation of genes encoding Trx/Prx and on the transcriptional and post
      transcriptional control exercised by these proteins on their putative targets. As
      another point of control, post-translational regulation of the proteins, such as
      S-nitrosylation and S-oxidation, is of increasing interest for its effect on
      protein structure and function. Special attention is given to the involvement of
      the Trx/Prx/Srx system and its redox state in plant signalling under stress, more
      specifically under abiotic stress conditions, as an important cue that influences
      plant yield and growth. This review focuses on the regulation of Trx and Prx
      through cysteine S-oxidation and/or S-nitrosylation, which affects their
      functionality. Some examples of redox regulation of transcription factors and Trx
      and Prx-related genes are also presented.

PMID- 25873658
TI  - C4 bioenergy crops for cool climates, with special emphasis on perennial C4
      grasses.
AB  - There is much interest in cultivating C4 perennial plants in northern climates
      where there is an abundance of land and a potential large market for biofuels. C4
      feedstocks can exhibit superior yields to C3 alternatives during the long warm
      days of summer at high latitude, but their summer success depends on an ability
      to tolerate deep winter cold, spring frosts, and early growth-season chill. Here,
      we review cold tolerance limits in C4 perennial grasses. Dozens of C4 species are
      known from high latitudes to 63  degrees N and elevations up to 5200 m,
      demonstrating that C4 plants can adapt to cold climates. Of the three leading C4
      grasses being considered for bioenergy production in cold climates--Miscanthus
      spp., switchgrass (Panicum virgatum), and prairie cordgrass (Spartina pectinata)-
      all are tolerant of cool temperatures (10-15  degrees C), but only cordgrass
      tolerates hard spring frosts. All three species overwinter as dormant rhizomes.
      In the productive Miscanthus*giganteus hybrids, exposure to temperatures below -3
      degrees C to -7  degrees C will kill overwintering rhizomes, while for upland
      switchgrass and cordgrass, rhizomes survive exposure to temperatures above -20 
      degrees C to -24  degrees C. Cordgrass emerges earlier than switchgrass and M.
      giganteus genotypes, but lacks the Miscanthus growth potential once warmer days
      of late spring arrive. To enable C4-based bioenergy production in colder
      climates, breeding priorities should emphasize improved cold tolerance of
      M.*giganteus, and enhanced productivity of switchgrass and cordgrass. This should
      be feasible in the near future, because wild populations of each species exhibit
      a diverse range of cold tolerance and growth capabilities.

PMID- 25873659
TI  - CaWRKY6 transcriptionally activates CaWRKY40, regulates Ralstonia solanacearum
      resistance, and confers high-temperature and high-humidity tolerance in pepper.
AB  - High temperature (HT), high humidity (HH), and pathogen infection often co-occur
      and negatively affect plant growth. However, these stress factors and plant
      responses are generally studied in isolation. The mechanisms of synergistic
      responses to combined stresses are poorly understood. We isolated the subgroup
      IIb WRKY family member CaWRKY6 from Capsicum annuum and performed quantitative
      real-time PCR analysis. CaWRKY6 expression was upregulated by individual or
      simultaneous treatment with HT, HH, combined HT and HH (HTHH), and Ralstonia
      solanacearum inoculation, and responded to exogenous application of jasmonic acid
      (JA), ethephon, and abscisic acid (ABA). Virus-induced gene silencing of CaWRKY6
      enhanced pepper plant susceptibility to R. solanacearum and HTHH, and
      downregulated the hypersensitive response (HR), JA-, ethylene (ET)-, and ABA
      induced marker gene expression, and thermotolerance-associated expression of
      CaHSP24, ER-small CaSHP, and Chl-small CaHSP. CaWRKY6 overexpression in pepper
      attenuated the HTHH-induced suppression of resistance to R. solanacearum
      infection. CaWRKY6 bound to and activated the CaWRKY40 promoter in planta, which
      is a pepper WRKY that regulates heat-stress tolerance and R. solanacearum
      resistance. CaWRKY40 silencing significantly blocked HR-induced cell death and
      reduced transcriptional expression of CaWRKY40. These data suggest that CaWRKY6
      is a positive regulator of R. solanacearum resistance and heat-stress tolerance,
      which occurs in part by activating CaWRKY40. 

PMID- 25873660
TI  - A genetic relationship between nitrogen use efficiency and seedling root traits
      in maize as revealed by QTL analysis.
AB  - That root system architecture (RSA) has an essential role in nitrogen acquisition
      is expected in maize, but the genetic relationship between RSA and nitrogen use
      efficiency (NUE) traits remains to be elucidated. Here, the genetic basis of RSA
      and NUE traits was investigated in maize using a recombination inbred line
      population that was derived from two lines contrasted for both traits. Under high
      nitrogen and low-nitrogen conditions, 10 NUE- and 9 RSA-related traits were
      evaluated in four field environments and three hydroponic experiments,
      respectively. In contrast to nitrogen utilization efficiency (NutE), nitrogen
      uptake efficiency (NupE) had significant phenotypic correlations with RSA,
      particularly the traits of seminal roots (r = 0.15-0.31) and crown roots (r =
      0.15-0.18). A total of 331 quantitative trait loci (QTLs) were detected,
      including 184 and 147 QTLs for NUE- and RSA-related traits, respectively. These
      QTLs were assigned into 64 distinct QTL clusters, and ~70% of QTLs for nitrogen
      efficiency (NUE, NupE, and NutE) coincided in clusters with those for RSA. Five
      important QTLs clusters at the chromosomal regions bin1.04, 2.04, 3.04,
      3.05/3.06, and 6.07/6.08 were found in which QTLs for both traits had favourable
      effects from alleles coming from the large-rooted and high-NupE parent.
      Introgression of these QTL clusters in the advanced backcross-derived lines
      conferred mean increases in grain yield of ~14.8% for the line per se and ~15.9%
      in the testcross. These results reveal a significant genetic relationship between
      RSA and NUE traits, and uncover the most promising genomic regions for marker
      assisted selection of RSA to improve NUE in maize. 

PMID- 25873661
TI  - Characterizing visible and invisible cell wall mutant phenotypes.
AB  - About 10% of a plant's genome is devoted to generating the protein machinery to
      synthesize, remodel, and deconstruct the cell wall. High-throughput genome
      sequencing technologies have enabled a reasonably complete inventory of wall
      related genes that can be assembled into families of common evolutionary origin.
      Assigning function to each gene family member has been aided immensely by
      identification of mutants with visible phenotypes or by chemical and
      spectroscopic analysis of mutants with 'invisible' phenotypes of modified cell
      wall composition and architecture that do not otherwise affect plant growth or
      development. This review connects the inference of gene function on the basis of
      deviation from the wild type in genetic functional analyses to insights provided
      by modern analytical techniques that have brought us ever closer to elucidating
      the sequence structures of the major polysaccharide components of the plant cell
      wall. 

PMID- 25873662
TI  - ROS and RNS in plant physiology: an overview.
AB  - The production of reactive oxygen species (ROS) is the unavoidable consequence of
      aerobic life. ROS is a collective term that includes both oxygen radicals, like
      superoxide (O 2. -) and hydroxyl (.OH) radicals, and other non-radicals such as
      hydrogen peroxide (H2O2), singlet oxygen ((1)O2 or (1)Deltag), etc. In plants,
      ROS are produced in different cell compartments and are oxidizing species,
      particularly hydroxyl radicals and singlet oxygen, that can produce serious
      damage in biological systems (oxidative stress). However, plant cells also have
      an array of antioxidants which, normally, can scavenge the excess oxidants
      produced and so avoid deleterious effects on the plant cell bio-molecules. The
      concept of 'oxidative stress' was re-evaluated in recent years and the term
      'oxidative signalling' was created. This means that ROS production, apart from
      being a potentially harmful process, is also an important component of the
      signalling network that plants use for their development and for responding to
      environmental challenges. It is known that ROS play an important role regulating
      numerous biological processes such as growth, development, response to biotic and
      environmental stresses, and programmed cell death. The term reactive nitrogen
      species (RNS) includes radicals like nitric oxide (NO. ) and nitric dioxide
      (NO2.), as well as non-radicals such as nitrous acid (HNO2) and dinitrogen
      tetroxide (N2O4), among others. RNS are also produced in plants although the
      generating systems have still not been fully characterized. Nitric oxide (NO.)
      has an important function as a key signalling molecule in plant growth,
      development, and senescence, and RNS, like ROS, also play an important role as
      signalling molecules in the response to environmental (abiotic) stress.
      Similarly, NO. is a key mediator, in co-operation with ROS, in the defence
      response to pathogen attacks in plants. ROS and RNS have been demonstrated to
      have an increasingly important role in biology and medicine.

PMID- 25873663
TI  - Measuring the mechanical properties of plant cells by combining micro-indentation
      with osmotic treatments.
AB  - Growth in plants results from the interaction between genetic and signalling
      networks and the mechanical properties of cells and tissues. There has been a
      recent resurgence in research directed at understanding the mechanical aspects of
      growth, and their feedback on genetic regulation. This has been driven in part by
      the development of new micro-indentation techniques to measure the mechanical
      properties of plant cells in vivo. However, the interpretation of indentation
      experiments remains a challenge, since the force measures results from a
      combination of turgor pressure, cell wall stiffness, and cell and indenter
      geometry. In order to interpret the measurements, an accurate mechanical model of
      the experiment is required. Here, we used a plant cell system with a simple
      geometry, Nicotiana tabacum Bright Yellow-2 (BY-2) cells, to examine the
      sensitivity of micro-indentation to a variety of mechanical and experimental
      parameters. Using a finite-element mechanical model, we found that, for
      indentations of a few microns on turgid cells, the measurements were mostly
      sensitive to turgor pressure and the radius of the cell, and not to the exact
      indenter shape or elastic properties of the cell wall. By complementing
      indentation experiments with osmotic experiments to measure the elastic strain in
      turgid cells, we could fit the model to both turgor pressure and cell wall
      elasticity. This allowed us to interpret apparent stiffness values in terms of
      meaningful physical parameters that are relevant for morphogenesis. 

PMID- 25873664
TI  - Deficit irrigation and sustainable water-resource strategies in agriculture for
      China's food security.
AB  - More than 70% of fresh water is used in agriculture in many parts of the world,
      but competition for domestic and industrial water use is intense. For future
      global food security, water use in agriculture must become sustainable.
      Agricultural water-use efficiency and water productivity can be improved at
      different points from the stomatal to the regional scale. A promising approach is
      the use of deficit irrigation, which can both save water and induce plant
      physiological regulations such as stomatal opening and reproductive and
      vegetative growth. At the scales of the irrigation district, the catchment, and
      the region, there can be many other components to a sustainable water-resources
      strategy. There is much interest in whether crop water use can be regulated as a
      function of understanding of physiological responses. If this is the case, then
      agricultural water resources can be reallocated to the benefit of the broader
      community. We summarize the extent of use and impact of deficit irrigation within
      China. A sustainable strategy for allocation of agricultural water resources for
      food security is proposed. Our intention is to build an integrative system to
      control crop water use during different cropping stages and actively regulate the
      plant's growth, productivity, and development based on physiological responses.
      This is done with a view to improving the allocation of limited agricultural
      water resources. 

PMID- 25873665
TI  - U-box E3 ubiquitin ligase PUB17 acts in the nucleus to promote specific immune
      pathways triggered by Phytophthora infestans.
AB  - Ubiquitination regulates many processes in plants, including immunity. The E3
      ubiquitin ligase PUB17 is a positive regulator of programmed cell death (PCD)
      triggered by resistance proteins CF4/9 in tomato. Its role in immunity to the
      potato late blight pathogen, Phytophthora infestans, was investigated here.
      Silencing StPUB17 in potato by RNAi and NbPUB17 in Nicotiana benthamiana by virus
      induced gene silencing (VIGS) each enhanced P. infestans leaf colonization. PAMP
      triggered immunity (PTI) transcriptional responses activated by flg22, and
      CF4/Avr4-mediated PCD were attenuated by silencing PUB17. However, silencing
      PUB17 did not compromise PCD triggered by P. infestans PAMP INF1, or co
      expression of R3a/AVR3a, demonstrating that not all PTI- and PCD-associated
      responses require PUB17. PUB17 localizes to the plant nucleus and especially in
      the nucleolus. Transient over-expression of a dominant-negative
      StPUB17(V314I,V316I) mutant, which retained nucleolar localization, suppressed
      CF4-mediated cell death and enhanced P. infestans colonization. Exclusion of the
      StPUB17(V314I,V316I) mutant from the nucleus abolished its dominant-negative
      activity, demonstrating that StPUB17 functions in the nucleus. PUB17 is a
      positive regulator of immunity to late blight that acts in the nucleus to promote
      specific PTI and PCD pathways. 

PMID- 25873666
TI  - Increased tolerance to salt stress in OPDA-deficient rice ALLENE OXIDE CYCLASE
      mutants is linked to an increased ROS-scavenging activity.
AB  - Salinity stress represents a global constraint for rice, the most important
      staple food worldwide. Therefore the role of the central stress signal jasmonate
      for the salt response was analysed in rice comparing the responses to salt stress
      for two jasmonic acid (JA) biosynthesis rice mutants (cpm2 and hebiba) impaired
      in the function of ALLENE OXIDE CYCLASE (AOC) and their wild type. The aoc
      mutants were less sensitive to salt stress. Interestingly, both mutants
      accumulated smaller amounts of Na(+) ions in their leaves, and showed better
      scavenging of reactive oxygen species (ROS) under salt stress. Leaves of the wild
      type and JA mutants accumulated similar levels of abscisic acid (ABA) under
      stress conditions, and the levels of JA and its amino acid conjugate, JA
      isoleucine (JA-Ile), showed only subtle alterations in the wild type. In
      contrast, the wild type responded to salt stress by strong induction of the JA
      precursor 12-oxophytodienoic acid (OPDA), which was not observed in the mutants.
      Transcript levels of representative salinity-induced genes were induced less in
      the JA mutants. The absence of 12-OPDA in the mutants correlated not only with a
      generally increased ROS-scavenging activity, but also with the higher activity of
      specific enzymes in the antioxidative pathway, such as glutathione S-transferase,
      and fewer symptoms of damage as, for example, indicated by lower levels of
      malondialdehyde. The data are interpreted in a model where the absence of OPDA
      enhanced the antioxidative power in mutant leaves. 

PMID- 25873667
TI  - First insights into the genotype-phenotype map of phenotypic stability in rye.
AB  - Improving phenotypic stability of crops is pivotal for coping with the
      detrimental impacts of climate change. The goal of this study was to gain first
      insights into the genetic architecture of phenotypic stability in cereals. To
      this end, we determined grain yield, thousand kernel weight, test weight, falling
      number, and both protein and soluble pentosan content for two large bi-parental
      rye populations connected through one common parent and grown in multi
      environmental field trials involving more than 15 000 yield plots. Based on these
      extensive phenotypic data, we calculated parameters for static and dynamic
      phenotypic stability of the different traits and applied linkage mapping using
      whole-genome molecular marker profiles. While we observed an absence of large
      effect quantitative trait loci (QTLs) underlying yield stability, large and
      stable QTLs were found for phenotypic stability of test weight, soluble pentosan
      content, and falling number. Applying genome-wide selection, which in contrast to
      marker-assisted selection also takes into account loci with small-effect sizes,
      considerably increased the accuracy of prediction of phenotypic stability for all
      traits by exploiting both genetic relatedness and linkage between single
      nucleotide polymorphisms and QTLs. We conclude that breeding for crop phenotypic
      stability can be improved in related populations using genomic selection
      approaches established upon extensive phenotypic data. 

PMID- 25873668
TI  - Pepper aldehyde dehydrogenase CaALDH1 interacts with Xanthomonas effector AvrBsT
      and promotes effector-triggered cell death and defence responses.
AB  - Xanthomonas type III effector AvrBsT induces hypersensitive cell death and
      defence responses in pepper (Capsicum annuum) and Nicotiana benthamiana. Little
      is known about the host factors that interact with AvrBsT. Here, we identified
      pepper aldehyde dehydrogenase 1 (CaALDH1) as an AvrBsT-interacting protein.
      Bimolecular fluorescence complementation and co-immunoprecipitation assays
      confirmed the interaction between CaALDH1 and AvrBsT in planta. CaALDH1:smGFP
      fluorescence was detected in the cytoplasm. CaALDH1 expression in pepper was
      rapidly and strongly induced by avirulent Xanthomonas campestris pv. vesicatoria
      (Xcv) Ds1 (avrBsT) infection. Transient co-expression of CaALDH1 with avrBsT
      significantly enhanced avrBsT-triggered cell death in N. benthamiana leaves.
      Aldehyde dehydrogenase activity was higher in leaves transiently expressing
      CaALDH1, suggesting that CaALDH1 acts as a cell death enhancer, independently of
      AvrBsT. CaALDH1 silencing disrupted phenolic compound accumulation, H2O2
      production, defence response gene expression, and cell death during avirulent Xcv
      Ds1 (avrBsT) infection. Transgenic Arabidopsis thaliana overexpressing CaALDH1
      exhibited enhanced defence response to Pseudomonas syringae pv. tomato and
      Hyaloperonospora arabidopsidis infection. These results indicate that cytoplasmic
      CaALDH1 interacts with AvrBsT and promotes plant cell death and defence
      responses. 

PMID- 25873669
TI  - Genetic diversity of stilbene metabolism in Vitis sylvestris.
AB  - Stilbenes, as important secondary metabolites of grapevine, represent central
      phytoalexins and therefore constitute an important element of basal immunity. In
      this study, potential genetic variation in Vitis vinifera ssp. sylvestris, the
      ancestor of cultivated grapevine, was sought with respect to their output of
      stilbenes and potential use for resistance breeding. Considerable variation in
      stilbene inducibility was identified in V. vinifera ssp. sylvestris. Genotypic
      differences in abundance and profiles of stilbenes that are induced in response
      to a UV-C pulse are shown. Two clusters of stilbene 'chemovars' emerged: one
      cluster showed quick and strong accumulation of stilbenes, almost exclusively in
      the form of non-glycosylated resveratrol and viniferin, while the second cluster
      accumulated fewer stilbenes and relatively high proportions of piceatannol and
      the glycosylated piceid. For all 86 genotypes, a time dependence of the stilbene
      pattern was observed: piceid, resveratrol, and piceatannol accumulated earlier,
      whereas the viniferins were found later. It was further observed that the
      genotypic differences in stilbene accumulation were preceded by differential
      accumulation of the transcripts for chalcone synthase (CHS) and stilbene-related
      genes: phenylalanine ammonium lyase (PAL), stilbene synthase (StSy), and
      resveratrol synthase (RS). A screen of the population with respect to
      susceptibility to downy mildew of grapevine (Plasmopara viticola) revealed
      considerable variability. The subpopulation of genotypes with high stilbene
      inducibility was significantly less susceptible as compared with low-stilbene
      genotypes, and for representative genotypes it could be shown that the
      inducibility of stilbene synthase by UV correlated with the inducibility by the
      pathogen. 

PMID- 25873670
TI  - ICE1 of Poncirus trifoliata functions in cold tolerance by modulating polyamine
      levels through interacting with arginine decarboxylase.
AB  - ICE1 (Inducer of CBF Expression 1) encodes a MYC-like basic helix-loop-helix
      transcription factor that acts as a central regulator of cold response. In this
      study, we elucidated the function and underlying mechanisms of PtrICE1 from
      trifoliate orange [Poncirus trifoliata (L.) Raf.]. PtrICE1 was upregulated by
      cold, dehydration, and salt, with the greatest induction under cold conditions.
      PtrICE1 was localized in the nucleus and could bind to a MYC-recognizing
      sequence. Ectopic expression of PtrICE1 in tobacco and lemon conferred enhanced
      tolerance to cold stresses at either chilling or freezing temperatures. Yeast two
      hybrid screening revealed that 21 proteins belonged to the PtrICE1 interactome,
      in which PtADC (arginine decarboxylase) was confirmed as a bona fide protein
      interacting with PtrICE1. Transcript levels of ADC genes in the transgenic lines
      were slightly elevated under normal growth condition but substantially increased
      under cold conditions, consistent with changes in free polyamine levels. By
      contrast, accumulation of the reactive oxygen species, H2O2 and O2 (-), was
      appreciably alleviated in the transgenic lines under cold stress. Higher
      activities of antioxidant enzymes, such as superoxide dismutase and catalase,
      were detected in the transgenic lines under cold conditions. Taken together,
      these results demonstrated that PtrICE1 plays a positive role in cold tolerance,
      which may be due to modulation of polyamine levels through interacting with the
      ADC gene. 

PMID- 25873671
TI  - Involvement of 14-3-3 protein GRF9 in root growth and response under polyethylene
      glycol-induced water stress.
AB  - Plant 14-3-3 proteins are phosphoserine-binding proteins that regulate a wide
      array of targets via direct protein-protein interactions. In this study, the role
      of a 14-3-3 protein, GRF9, in plant response to water stress was investigated.
      Arabidopsis wild-type, GRF9-deficient mutant (grf9), and GRF9-overexpressing (OE)
      plants were treated with polyethylene glycol (PEG) to induce mild water stress.
      OE plant showed better whole-plant growth and root growth than the wild type
      under normal or water stress conditions while the grf9 mutant showed worse
      growth. In OE plants, GRF9 favours the allocation of shoot carbon to roots. In
      addition, GRF9 enhanced proton extrusion, mainly in the root elongation zone and
      root hair zone, and maintained root growth under mild water stress. Grafting
      among the wild type, OE, and grf9 plants showed that when OE plants were used as
      the scion and GRF9 was overexpressed in the shoot, it enhanced sucrose transport
      into the root, and when OE plants were used as rootstock and GRF9 was
      overexpressed in the root, it caused more release of protons into the root
      surface under water stress. Taken together, the results suggest that under PEG
      induced water stress, GRF9 is involved in allocating more carbon from the shoot
      to the root and enhancing proton secretion in the root growing zone, and this
      process is important for root response to mild water stress. 

PMID- 25873672
TI  - Development and use of bioenergy feedstocks for semi-arid and arid lands.
AB  - Global climate change is predicted to increase heat, drought, and soil-drying
      conditions, and thereby increase crop sensitivity to water vapour pressure
      deficit, resulting in productivity losses. Increasing competition between
      agricultural freshwater use and municipal or industrial uses suggest that crops
      with greater heat and drought durability and greater water-use efficiency will be
      crucial for sustainable biomass production systems in the future. Agave
      (Agavaceae) and Opuntia (Cactaceae) represent highly water-use efficient
      bioenergy crops that could diversify bioenergy feedstock supply yet preserve or
      expand feedstock production into semi-arid, abandoned, or degraded agricultural
      lands, and reclaim drylands. Agave and Opuntia are crassulacean acid metabolism
      species that can achieve high water-use efficiencies and grow in water-limited
      areas with insufficient precipitation to support traditional C3 or C4 bioenergy
      crops. Both Agave and Opuntia have the potential to produce above-ground biomass
      rivalling that of C3 and C4 crops under optimal growing conditions. The low
      lignin and high amorphous cellulose contents of Agave and Opuntia lignocellulosic
      biomass will be less recalcitrant to deconstruction than traditional feedstocks,
      as confirmed by pretreatments that improve saccharification of Agave. Refined
      environmental productivity indices and geographical information systems modelling
      have provided estimates of Agave and Opuntia biomass productivity and terrestrial
      sequestration of atmospheric CO2; however, the accuracy of such modelling efforts
      can be improved through the expansion of field trials in diverse geographical
      settings. Lastly, life cycle analysis indicates that Agave would have
      productivity, life cycle energy, and greenhouse gas balances comparable or
      superior to those of traditional bioenergy feedstocks, but would be far more
      water-use efficient. 

PMID- 25873674
TI  - Preventing lodging in bioenergy crops: a biomechanical analysis of maize stalks
      suggests a new approach.
AB  - The hypothetical ideal for maize (Zea mays) bioenergy production would be a no
      waste plant: high-yielding, with silage that is easily digestible for conversion
      to biofuel. However, increased digestibility is typically associated with low
      structural strength and a propensity for lodging. The solution to this dilemma
      may lie in our ability to optimize maize morphology using tools from structural
      engineering. To investigate how material (tissue) and geometric (morphological)
      factors influence stalk strength, detailed structural models of the maize stalk
      were created using finite-element software. Model geometry was obtained from high
      resolution x-ray computed tomography (CT) scans, and scan intensity information
      was integrated into the models to infer inhomogeneous material properties. A
      sensitivity analysis was performed by systematically varying material properties
      over broad ranges, and by modifying stalk geometry. Computational models
      exhibited realistic stress and deformation patterns. In agreement with natural
      failure patterns, maximum stresses were predicted near the node. Maximum stresses
      were observed to be much more sensitive to changes in dimensions of the stalk
      cross section than they were to changes in material properties of stalk
      components. The average sensitivity to geometry was found to be more than 10-fold
      higher than the average sensitivity to material properties. These results suggest
      a new strategy for the breeding and development of bioenergy maize varieties in
      which tissue weaknesses are counterbalanced by relatively small increases (e.g.
      5%) in stalk diameter that reduce structural stresses. 

PMID- 25873673
TI  - Magnetic resonance imaging of sugar beet taproots in soil reveals growth
      reduction and morphological changes during foliar Cercospora beticola
      infestation.
AB  - Cercospora leaf spot (CLS) infection can cause severe yield loss in sugar beet.
      Introduction of Cercospora-resistant varieties in breeding programmes is
      important for plant protection to reduce both fungicide applications and the risk
      of the development of fungal resistance. However, in vivo monitoring of the sugar
      containing taproots at early stages of foliar symptoms and the characterization
      of the temporal development of disease progression has proven difficult. Non
      invasive magnetic resonance imaging (MRI) measurements were conducted to quantify
      taproot development of genotypes with high (HS) and low (LS) levels of
      susceptibility after foliar Cercospora inoculation. Fourteen days post
      inoculation (dpi) the ratio of infected leaf area was still low (~7%) in both the
      HS and LS genotypes. However, during this period, the volumetric growth of the
      taproot had already started to decrease. Additionally, inoculated plants showed a
      reduction of the increase in width of inner cambial rings while the width of
      outer rings increased slightly compared with non-inoculated plants. This response
      partly compensated for the reduced development of inner rings that had a vascular
      connection with Cercospora-inoculated leaves. Hence, alterations in taproot
      anatomical features such as volume and cambial ring development can be non
      invasively detected already at 14 dpi, providing information on the early impact
      of the infection on whole-plant performance. All these findings show that MRI is
      a suitable tool to identify promising candidate parent lines with improved
      resistance to Cercospora, for example with comparatively lower taproot growth
      reduction at early stages of canopy infection, for future introduction into
      breeing programmes. 

PMID- 25873675
TI  - Differential effects of lesion mimic mutants in barley on disease development by
      facultative pathogens.
AB  - Lesion mimic mutants display spontaneous necrotic spots and chlorotic leaves as a
      result of mis-regulated cell death programmes. Typically these mutants have
      increased resistance to biotrophic pathogens but their response to facultative
      fungi that cause necrotrophic diseases is less well studied. The effect of
      altered cell death regulation on the development of disease caused by Ramularia
      collo-cygni, Fusarium culmorum and Oculimacula yallundae was explored using a
      collection of barley necrotic (nec) lesion mimic mutants. nec8 mutants displayed
      lower levels of all three diseases compared to nec9 mutants, which had increased
      R. collo-cygni but decreased F. culmorum disease symptoms. nec1 mutants reduced
      disease development caused by both R. collo-cygni and F. culmorum. The severity
      of the nec1-induced lesion mimic phenotype and F. culmorum symptom development
      was reduced by mutation of the negative cell death regulator MLO. The significant
      reduction in R. collo-cygni symptoms caused by nec1 was completely abolished in
      the presence of the mlo-5 allele and both symptoms and fungal biomass were
      greater than in the wild-type. These results indicate that physiological pathways
      involved in regulation of cell death interact with one another in their effects
      on different fungal pathogens. 

PMID- 25873676
TI  - Evidence of various mechanisms of Cd sequestration in the hyperaccumulator
      Arabidopsis halleri, the non-accumulator Arabidopsis lyrata, and their progenies
      by combined synchrotron-based techniques.
AB  - Arabidopsis halleri is a model plant for Zn and Cd hyperaccumulation. The
      objective of this study was to determine the relationship between the chemical
      forms of Cd, its distribution in leaves, and Cd accumulation and tolerance. An
      interspecific cross was carried out between A. halleri and the non-tolerant and
      non-hyperaccumulating relative A. lyrata providing progenies segregating for Cd
      tolerance and accumulation. Cd speciation and distribution were investigated
      using X-ray absorption spectroscopy and microfocused X-ray fluorescence. In A.
      lyrata and non-tolerant progenies, Cd was coordinated by S atoms only or with a
      small contribution of O groups. Interestingly, the proportion of O ligands
      increased in A. halleri and tolerant progenies, and they were predominant in most
      of them, while S ligands were still present. Therefore, the binding of Cd with O
      ligands was associated with Cd tolerance. In A. halleri, Cd was mainly located in
      the xylem, phloem, and mesophyll tissue, suggesting a reallocation process for Cd
      within the plant. The distribution of the metal at the cell level was further
      discussed. In A. lyrata, the vascular bundles were also Cd enriched, but the
      epidermis was richer in Cd as compared with the mesophyll. Cd was identified in
      trichomes of both species. This work demonstrated that both Cd speciation and
      localization were related to the tolerance character of the plant. 

PMID- 25873677
TI  - Intraspecific variability of cadmium tolerance and accumulation, and cadmium
      induced cell wall modifications in the metal hyperaccumulator Arabidopsis
      halleri.
AB  - Certain molecular mechanisms of Cd tolerance and accumulation have been
      identified in the model species Arabidopsis halleri, while intraspecific
      variability of these traits and the mechanisms of shoot detoxification were
      little addressed. The Cd tolerance and accumulation of metallicolous and non
      metallicolous A. halleri populations from different genetic units were tested in
      controlled conditions. In addition, changes in shoot cell wall composition were
      investigated using Fourier transform infrared spectroscopy. Indeed, recent works
      on A. halleri suggest Cd sequestration both inside cells and in the cell
      wall/apoplast. All A. halleri populations tested were hypertolerant to Cd, and
      the metallicolous populations were on average the most tolerant. Accumulation was
      highly variable between and within populations, and populations that were non
      accumulators of Cd were identified. The effect of Cd on the cell wall composition
      was quite similar in the sensitive species A. lyrata and in A. halleri
      individuals; the pectin/polysaccharide content of cell walls seems to increase
      after Cd treatment. Nevertheless, the changes induced by Cd were more pronounced
      in the less tolerant individuals, leading to a correlation between the level of
      tolerance and the extent of modifications. This work demonstrated that Cd
      tolerance and accumulation are highly variable traits in A. halleri, suggesting
      adaptation at the local scale and involvement of various molecular mechanisms.
      While in non-metallicolous populations drastic modifications of the cell wall
      occur due to higher Cd toxicity and/or Cd immobilization in this compartment, the
      increased tolerance of metallicolous populations probably involves other
      mechanisms such as vacuolar sequestration. 

PMID- 25873678
TI  - Sucrose phosphate synthase and sucrose phosphate phosphatase interact in planta
      and promote plant growth and biomass accumulation.
AB  - Bioinformatic analysis indicates that sucrose phosphate synthase (SPS) contains a
      putative C-terminal sucrose phosphate phosphatase (SPP)-like domain that may
      facilitates the binding of SPP. If an SPS-SPP enzyme complex exists, it may
      provide sucrose biosynthesis with an additional level of regulation, forming a
      direct metabolic channel for sucrose-6-phosphate between these two enzymes.
      Herein, the formation of an enzyme complex between SPS and SPP was examined, and
      the results from yeast two-hybrid experiments suggest that there is indeed an
      association between these proteins. In addition, in planta bioluminescence
      resonance energy transfer (BRET) was observed in Arabidopsis seedlings, providing
      physical evidence for a protein interaction in live cells and in real time.
      Finally, bimolecular fluorescence complementation (BiFC) was employed in an
      attempt to detect SPS-SPP interactions visually. The findings clearly
      demonstrated that SPS interacts with SPP and that this interaction impacts
      soluble carbohydrate pools and affects carbon partitioning to starch. Moreover, a
      fusion construct between the two genes promotes plant growth in both transgenic
      Arabidopsis and hybrid poplar. 

PMID- 25873679
TI  - Sucrose is an early modulator of the key hormonal mechanisms controlling bud
      outgrowth in Rosa hybrida.
AB  - Sugar has only recently been identified as a key player in triggering bud
      outgrowth, while hormonal control of bud outgrowth is already well established.
      To get a better understanding of sugar control, the present study investigated
      how sugar availability modulates the hormonal network during bud outgrowth in
      Rosa hybrida. Other plant models, for which mutants are available, were used when
      necessary. Buds were grown in vitro to manipulate available sugars. The temporal
      patterns of the hormonal regulatory network were assessed in parallel with bud
      outgrowth dynamics. Sucrose determined bud entrance into sustained growth in a
      concentration-dependent manner. Sustained growth was accompanied by sustained
      auxin production in buds, and sustained auxin export in a DR5::GUS-expressing pea
      line. Several events occurred ahead of sucrose-stimulated bud outgrowth. Sucrose
      upregulated early auxin synthesis genes (RhTAR1, RhYUC1) and the auxin efflux
      carrier gene RhPIN1, and promoted PIN1 abundance at the plasma membrane in a
      pPIN1::PIN1-GFP-expressing tomato line. Sucrose downregulated both RwMAX2,
      involved in the strigolactone-transduction pathway, and RhBRC1, a repressor of
      branching, at an early stage. The presence of sucrose also increased stem
      cytokinin content, but sucrose-promoted bud outgrowth was not related to that
      pathway. In these processes, several non-metabolizable sucrose analogues induced
      sustained bud outgrowth in R. hybrida, Pisum sativum, and Arabidopsis thaliana,
      suggesting that sucrose was involved in a signalling pathway. In conclusion, we
      identified potential hormonal candidates for bud outgrowth control by sugar. They
      are central to future investigations aimed at disentangling the processes that
      underlie regulation of bud outgrowth by sugar. 

PMID- 25873680
TI  - Sub-zero cold tolerance of Spartina pectinata (prairie cordgrass) and Miscanthus
      * giganteus: candidate bioenergy crops for cool temperate climates.
AB  - Miscanthus * giganteus grown in cool temperate regions of North America and
      Europe can exhibit severe mortality in the year after planting, and poor frost
      tolerance of leaves. Spartina pectinata (prairie cordgrass), a productive C4
      perennial grass native to North America, has been suggested as an alternative
      biofuel feedstock for colder regions; however, its cold tolerance relative to M.
      * giganteus is uncertain. Here, we compare the cold tolerance thresholds for
      winter-dormant rhizomes and spring/summer leaves of M. * giganteus and three
      accessions of S. pectinata. All genotypes were planted at a field site in
      Ontario, Canada. In November and February, the temperatures corresponding to 50%
      rhizome mortality (LT(50)) were near -24 degrees C for S. pectinata and -4
      degrees C for M. * giganteus. In late April, the LT50 of rhizomes rose to -10
      degrees C for S. pectinata but remained near -4 degrees C for M. * giganteus.
      Twenty percent of the M. * giganteus rhizomes collected in late April were dead
      while S. pectinata rhizomes showed no signs of winter injury. Photosynthesis and
      electrolyte leakage measurements in spring and summer demonstrate that S.
      pectinata leaves have greater frost tolerance in the field. For example, S.
      pectinata leaves remained viable above -9 degrees C while the mortality threshold
      was near -5 degrees C for M. * giganteus. These results indicate M. * giganteus
      will be unsuitable for production in continental interiors of cool-temperate
      climate zones unless freezing and frost tolerance are improved. By contrast, S.
      pectinata has the freezing and frost tolerance required for a higher-latitude
      bioenergy crop. 

PMID- 25873681
TI  - Variation and impact of drought-stress patterns across upland rice target
      population of environments in Brazil.
AB  - The upland rice (UR) cropped area in Brazil has decreased in the last decade.
      Importantly, a portion of this decrease can be attributed to the current UR
      breeding programme strategy, according to which direct grain yield selection is
      targeted primarily to the most favourable areas. New strategies for more
      efficient crop breeding under non-optimal conditions are needed for Brazil's UR
      regions. Such strategies should include a classification of spatio-temporal yield
      variations in environmental groups, as well as a determination of prevalent
      drought types and their characteristics (duration, intensity, phenological
      timing, and physiological effects) within those environmental groups. This study
      used a process-based crop model to support the Brazilian UR breeding programme in
      their efforts to adopt a new strategy that accounts for the varying range of
      environments where UR is currently cultivated. Crop simulations based on a
      commonly grown cultivar (BRS Primavera) and statistical analyses of simulated
      yield suggested that the target population of environments can be divided into
      three groups of environments: a highly favorable environment (HFE, 19% of area),
      a favorable environment (FE, 44%), and least favourable environment (LFE, 37%).
      Stress-free conditions dominated the HFE group (69% likelihood) and reproductive
      stress dominated the LFE group (68% likelihood), whereas reproductive and
      terminal drought stress were found to be almost equally likely to occur in the FE
      group. For the best and worst environments, we propose specific adaptation
      focused on the representative stress, while for the FE, wide adaptation to
      drought is suggested. 'Weighted selection' is also a possible strategy for the FE
      and LFE environment groups. 

PMID- 25873682
TI  - Autumnal leaf senescence in Miscanthus * giganteus and leaf [N] differ by stand
      age.
AB  - Poor first winter survival in Miscanthus * giganteus has been anecdotally
      attributed to incomplete first autumn senescence, but these assessments never
      paired first-year with older M. * giganteus in side-by-side trials to separate
      the effect of weather from stand age. Here CO2 assimilation rate (A), photosystem
      II efficiency (PhiPSII), and leaf N concentration ([N]) were used to directly
      compare senescence in first, second, and third-year stands of M. * giganteus.
      Three M. * giganteus fields were planted with eight plots, one field each in
      2009, 2010, and 2011. To quantify autumnal leaf senescence of plants within each
      stand age, photosynthetic and leaf [N] measurements were made twice weekly from
      early September until a killing frost. Following chilling events (daily
      temperature averages below 10  degrees C), photosynthetic rates in first year
      plants rebounded to a greater degree than those in second- and third-year plants.
      By the end of the growing season, first-year M. * giganteus had A and PhiPSII
      rates up to 4 times greater than third-year M. * giganteus, while leaf [N] was up
      to 2.4 times greater. The increased photosynthetic capability and leaf N status
      in first-year M. * giganteus suggests that the photosynthetic apparatus was not
      dismantled before a killing frost, thus potentially limiting nutrient
      translocation, and may explain why young M. * giganteus stands do not survive
      winter when older stands do. Because previous senescence research has primarily
      focused on annual or woody species, our results suggest that M. * giganteus may
      be an interesting herbaceous perennial system to investigate the interactive
      effects of plant ageing and nutrient status on senescence and may highlight
      management strategies that could potentially increase winter survival rates in
      first-year stands. 

PMID- 25873683
TI  - Microalgae for economic applications: advantages and perspectives for bioethanol.
AB  - Renewable energy has attracted significant interest in recent years as a result
      of sustainability, environmental impact, and socio-economic considerations. Given
      existing technological knowledge and based on projections relating to biofuels
      derived from microalgae, microalgal feedstock is considered to be one of the most
      important renewable energy sources potentially available for industrial
      production. Therefore, this review examines microalgal bioethanol technology,
      which converts biomass from microalgae to fuel, the chemical processes involved,
      and possible ways of increasing the bioethanol yield, such as abiotic factors and
      genetic manipulation of fermenting organisms. 

PMID- 25873684
TI  - Regulation of chloroplast development and function by cytokinin.
AB  - A role of the plant hormone cytokinin in regulating the development and activity
      of chloroplasts was described soon after its discovery as a plant growth
      regulator more than 50 years ago. Its promoting action on chloroplast
      ultrastructure and chlorophyll synthesis has been reported repeatedly, especially
      during etioplast-to-chloroplast transition. Recently, a protective role of the
      hormone for the photosynthetic apparatus during high light stress was shown.
      Details about the molecular mechanisms of cytokinin action on plastids are
      accumulating from genetic and transcriptomic studies. The cytokinin receptors
      AHK2 and AHK3 are mainly responsible for the transduction of the cytokinin signal
      to B-type response regulators, in particular ARR1, ARR10, and ARR12, which are
      transcription factors of the two-component system mediating cytokinin functions.
      Additional transcription factors linking cytokinin and chloroplast development
      include CGA1, GNC, HY5, GLK2, and CRF2. In this review, we summarize early and
      more recent findings of the long-known relationship between the hormone and the
      organelle and describe crosstalk between cytokinin, light, and other hormones
      during chloroplast development. 

PMID- 25873686
TI  - On the relationship between endoreduplication and collet hair initiation and tip
      growth, as determined using six Arabidopsis thaliana root-hair mutants.
AB  - A positive correlation between nuclear DNA content and cell size, as postulated
      by the karyoplasmic theory, has been confirmed in many plant tissues. However,
      there is also evidence suggesting that there are exceptions. While in previous
      reports the cell size:ploidy relationship was studied in intact tissues
      containing cells of different sizes, here simultaneously developing single cells
      of collet hairs were used to study endoreduplication in Arabidopsis thaliana
      mutants that produce hairs of variable size and morphology. Endoreduplication in
      the root and collet zones of six different root-hair mutants was analysed before
      and after collet hair development using flow cytometry and confocal microscopy.
      Additionally, the changes in nuclear size (ploidy), shape, and movement in
      developing collet hairs of a hybrid between Arabidopsis transgenic line NLS-GFP
      GUS and the rhd3 (root hair defective3) mutant were followed using time-lapse
      confocal microscopy. In this hybrid endoreduplication in the collet hairs was
      disturbed. However, based on the analyses of all mutants, no correlation was
      found between hair length and the ploidy of the cells in the collet and root
      regions. The results indicate that the karyoplasmic ratio is maintained at the
      beginning of collet-hair development, but tip growth proceeds in a DNA-amount
      independent manner. The final size of a collet hair appears to be dependent more
      on genetic modifiers governing general cell physiology than on its DNA content. 

PMID- 25873685
TI  - Expression patterns of Brassica napus genes implicate IPT, CKX, sucrose
      transporter, cell wall invertase, and amino acid permease gene family members in
      leaf, flower, silique, and seed development.
AB  - Forage brassica (Brassica napus cv. Greenland) is bred for vegetative growth and
      biomass production, while its seed yield remains to be improved for seed
      producers without affecting forage yield and quality. Cytokinins affect seed
      yield by influencing flower, silique and seed number, and seed size. To identify
      specific cytokinin gene family members as targets for breeding, as well as genes
      associated with yield and/or quality, a B. napus transcriptome was obtained from
      a mixed sample including leaves, flower buds and siliques of various stages. Gene
      families for cytokinin biosynthesis (BnIPT1, 2, 3, 5, 7, 8 and 9), cytokinin
      degradation (BnCKX1 to BnCKX7), cell wall invertase (BnCWINV1 to BnCWINV6), sugar
      transporter (BnSUT1 to BnSUT6) and amino acid permease (BnAAP1 to BnAAP8) were
      identified. As B. napus is tetraploid, homoeologues of each gene family member
      were sought. Using multiple alignments and phylogenetic analysis, the parental
      genomes of the two B. napus homoeologues could be differentiated. RT-qPCR was
      then used to determine the expression of gene family members and their
      homoeologues in leaves, flowers, siliques and seeds of different developmental
      stages. The expression analysis showed both temporal and organ-specific
      expression profiles among members of these multi-gene families. Several pairs of
      homoeologues showed differential expression, both in terms of level of expression
      and differences in temporal or organ-specificity. BnCKX2 and 4 were identified as
      targets for TILLING, EcoTILLING and MAS. 

PMID- 25873687
TI  - Polyphenol oxidase in leaves: is there any significance to the chloroplastic
      localization?
AB  - Polyphenol oxidase (PPO) catalyses the oxidation of monophenols and/or o
      diphenols to o-quinones with the concomitant reduction of oxygen to water which
      results in protein complexing and the formation of brown melanin pigments. The
      most frequently suggested role for PPO in plants has been in defence against
      herbivores and pathogens, based on the physical separation of the chloroplast
      localized enzyme from the vacuole-localized substrates. The o-quinone-protein
      complexes, formed as a consequence of cell damage, may reduce the nutritional
      value of the tissue and thereby reduce predation but can also participate in the
      formation of structural barriers against invading pathogens. However, since a
      sufficient level of compartmentation-based regulation could be accomplished if
      PPO was targeted to the cytosol, the benefit derived by some plant species in
      having PPO present in the chloroplast lumen remains an intriguing question. So is
      there more to the chloroplastic location of PPO? An interaction between PPO
      activity and photosynthesis has been proposed on more than one occasion but, to
      date, evidence either for or against direct involvement has been equivocal, and
      the lack of identified chloroplastic substrates remains an issue. Similarly, PPO
      has been suggested to have both pro- and anti-oxidant functions. Nevertheless,
      several independent lines of evidence suggest that PPO responds to environmental
      conditions and could be involved in the response of plants to abiotic stress.
      This review highlights our current understanding of the in vivo functions of PPO
      and considers the potential opportunities it presents for exploitation to
      increase stress tolerance in food crops. 

PMID- 25873688
TI  - Thou shalt not kill.

PMID- 25873690
TI  - Evolving ideas in primary care.

PMID- 25873692
TI  - Is physician-assisted death in anyone's best interest? Yes.

PMID- 25873693
TI  - Is physician-assisted death in anyone's best interest? No.

PMID- 25873696
TI  - Resiliency training.

PMID- 25873697
TI  - Resident speaks about mental health.

PMID- 25873698
TI  - Job-sharing story.

PMID- 25873699
TI  - Geography aside.

PMID- 25873700
TI  - End-of-life issues in advanced dementia: Part 1: goals of care, decision-making
      process, and family education.
AB  - OBJECTIVE: To review the issues with setting goals of care for patients with
      advanced dementia, describe the respective roles of the physician and the
      patient's family in the decision-making process, and suggest ways to support
      families who need more information about the care options. SOURCES OF
      INFORMATION: Ovid MEDLINE was searched for relevant articles that were published
      before March 7, 2014. There were no level I studies identified; most articles
      provided level III evidence. MAIN MESSAGE: For patients with advanced dementia,
      their families have an important role in medical decision making. Families should
      receive timely information about the course of dementia and the care options.
      They need to understand that a palliative approach to care might be appropriate
      and does not mean abandonment of the patient. They might also want clarification
      about their role in the decision-making process, especially if withholding or
      withdrawing life-prolonging measures are considered. CONCLUSION: Physicians
      should consider advanced dementia as a terminal disease for which there is a
      continuum of care that goes from palliative care with life-extending measures to
      symptomatic interventions only. Clarification of goals of care and family
      education are of paramount importance to avoid unwanted and burdensome
      interventions.

PMID- 25873701
TI  - End-of-life issues in advanced dementia: Part 2: management of poor nutritional
      intake, dehydration, and pneumonia.
AB  - OBJECTIVE: To answer frequently asked questions about management of end-stage
      pneumonia, poor nutritional intake, and dehydration in advanced dementia. SOURCES
      OF INFORMATION: Ovid MEDLINE was searched for relevant articles published until
      February 2015. No level I studies were identified; most articles provided level
      III evidence. The symptom management suggestions are partially based on recent
      participation in a Delphi procedure to develop a guideline for optimal symptom
      relief for patients with pneumonia and dementia. MAIN MESSAGE: Feeding tubes are
      not recommended for patients with end-stage dementia. Comfort feeding by hand is
      preferable. Use of parenteral hydration might be helpful but can also contribute
      to discomfort at the end of life. Withholding or withdrawing artificial nutrition
      and hydration is generally not associated with manifestations of discomfort if
      mouth care is adequate. Because pneumonia usually causes considerable discomfort,
      clinicians should pay attention to symptom control. Sedation for agitation is
      often useful in patients with dementia in the terminal phase. CONCLUSION:
      Symptomatic care is an appropriate option for end-stage manifestations of
      advanced dementia. The proposed symptom management guidelines are based on a
      literature review and expert consensus.

PMID- 25873702
TI  - How much did you take? Reviewing acetaminophen toxicity.

PMID- 25873703
TI  - Antiviral medications for influenza.

PMID- 25873705
TI  - Uncertainty in the age of answers.

PMID- 25873704
TI  - Advance directives: survey of primary care patients.
AB  - OBJECTIVE: To establish the prevalence of patients with advance directives in a
      family practice, and to describe patients' perspectives on a family doctor's role
      in initiating discussions about advance directives. DESIGN: A self-administered
      patient questionnaire. SETTING: A busy urban family medicine teaching clinic in
      Hamilton, Ont. PARTICIPANTS: A convenience sample of adult patients attending the
      clinic over the course of a typical business week. MAIN OUTCOME MEASURES: The
      prevalence of advance directives in the patient population was determined, and
      the patients' expectations regarding the role of their family doctors were
      elucidated. RESULTS: The survey population consisted of 800 participants (a
      response rate of 72.5%) well distributed across age groups; 19.7% had written
      advance directives and 43.8% had previously discussed the topic of advance
      directives, but only 4.3% of these discussions had occurred with family doctors.
      In 5.7% of cases, a family physician had raised the issue; 72.3% of respondents
      believed patients should initiate the discussion. Patients who considered advance
      directives extremely important were significantly more likely to want their
      family doctors to start the conversation (odds ratio 3.98; P < .05). CONCLUSION:
      Advance directives were not routinely addressed in the family practice. Most
      patients preferred to initiate the discussion of advance directives. However,
      patients who considered the subject extremely important wanted their family
      doctors to initiate the discussion.

PMID- 25873706
TI  - Zaharo Katsios MD CCFP.

PMID- 25873707
TI  - Patients with multiple comorbidities: simple teaching strategy.

PMID- 25873709
TI  - Linking health databases for research.

PMID- 25873711
TI  - Patient and public engagement.

PMID- 25873712
TI  - Rebuttal: Is physician-assisted death in anyone's best interest? Yes.

PMID- 25873713
TI  - Rebuttal: Is physician-assisted death in anyone's best interest? No.

PMID- 25873716
TI  - Dying at home: experience of the Verdun local community service centre.
AB  - OBJECTIVE: To demonstrate that it is possible for a team of palliative care
      nurses in an urban centre to care for more than 50% of their terminally ill
      patients at home until they die, and that medical care delivered in the home is a
      determining factor in death at home versus death in a hospital. DESIGN: Analysis
      of place of death of terminally ill patients who died in 2012 and 2013 (N = 212)
      and who had been cared for by palliative care nurses, by type of medical care.
      SETTING: The centre local de services communautaires (CLSC) in Verdun, Que, an
      urban neighbourhood in southwest Montreal. PARTICIPANTS: A total of 212
      terminally ill patients. MAIN OUTCOME MEASURES: Rate of deaths at home. RESULTS:
      Of the 212 patients cared for at home by palliative care nurses, 56.6% died at
      home; 62.6% received medical home care from CLSC physicians, compared with 5.0%
      who did not receive medical home care from any physician. CONCLUSION: Combined
      with a straightforward restructuring of the nursing care delivered by CLSCs,
      development of medical services delivered in the home would enable the more than
      50% of terminally ill patients in Quebec who are cared for by CLSCs to die at
      home--something that most of them wish for.

PMID- 25873718
TI  - Quantitative analysis of localized sources identified by focal impulse and rotor
      modulation mapping in atrial fibrillation.
AB  - BACKGROUND: New approaches to ablation of atrial fibrillation (AF) include focal
      impulse and rotor modulation (FIRM) mapping, and initial results reported with
      this technique have been favorable. We sought to independently evaluate the
      approach by analyzing quantitative characteristics of atrial electrograms used to
      identify rotors and describe acute procedural outcomes of FIRM-guided ablation.
      METHODS AND RESULTS: All FIRM-guided ablation procedures (n=24; 50% paroxysmal)
      at University of California, Los Angeles Medical Center were included for
      analysis. During AF, unipolar atrial electrograms collected from a 64-pole basket
      catheter were used to construct phase maps and identify putative AF sources.
      These sites were targeted for ablation, in conjunction with pulmonary vein
      isolation in most patients (n=19; 79%). All patients had rotors identified (mean,
      2.3+/-0.9 per patient; 72% in left atrium). Prespecified acute procedural end
      point was achieved in 12 of 24 (50%) patients: AF termination (n=1), organization
      (n=3), or >10% slowing of AF cycle length (n=8). Basket electrodes were within 1
      cm of 54% of left atrial surface area, and a mean of 31 electrodes per patient
      showed interpretable atrial electrograms. Offline analysis revealed no
      differences between rotor and distant sites in dominant frequency or Shannon
      entropy. Electroanatomic mapping showed no rotational activation at FIRM
      identified rotor sites in 23 of 24 patients (96%). CONCLUSIONS: FIRM-identified
      rotor sites did not exhibit quantitative atrial electrogram characteristics
      expected from rotors and did not differ quantitatively from surrounding tissue.
      Catheter ablation at these sites, in conjunction with pulmonary vein isolation,
      resulted in AF termination or organization in a minority of patients (4/24; 17%).
      Further validation of this approach is necessary.

PMID- 25873719
TI  - Catheter ablation of ventricular tachycardia and mortality in patients with
      nonischemic dilated cardiomyopathy: can noninducibility after ablation be a
      predictor for reduced mortality?
AB  - BACKGROUND: Data on outcomes after catheter ablation of ventricular tachycardia
      (VT) in patients with nonischemic dilated cardiomyopathy (NIDCM) are
      insufficient. We aimed to investigate the effects of successful catheter ablation
      of VT on cardiac mortality in patients with NIDCM. METHODS AND RESULTS: One
      hundred two patients with NIDCM (86 men; mean age, 58.8+/-15.2 years; mean
      ejection fraction, 33.3+/-11.9%) underwent VT ablation. After catheter ablation,
      a programmed ventricular stimulation to test for success was performed. Complete
      VT noninducibility was achieved in 62 (61%) patients and partial success or
      failure in 32 (31%) patients. During 2 years of follow-up, VT recurrence was
      observed in 33 patients (53%) without inducible VTs and in 24 patients (75%) with
      inducible VT inducible (P=0.041). VT inducibility was associated with higher VT
      recurrence (adjusted hazard ratio, 1.84; 95% confidence interval, 1.08-3.13;
      P=0.025). The primary end point of all-cause mortality was reached in 9 patients
      (15%) with noninducible VTs versus 11 patients (34%) with inducible sustained VTs
      (P=0.026). VT inducibility was associated with all-cause mortality (adjusted
      hazard ratio, 2.73; 95% confidence interval, 1.003-7.43; P=0.049). CONCLUSIONS:
      In patients with NIDCM and recurrent sustained VTs, a complete ablation of all
      inducible VTs may be achieved in 60% of the cases. The complete noninducibility
      may be a preferable end point of ablation because it was associated with better
      long-term success. Importantly, if possible to achieve through ablation, a
      complete VT noninducibility was associated with reduction of the likelihood for
      all-cause mortality in patients with NIDCM.

PMID- 25873720
TI  - Monitoring vascular permeability and remodeling after endothelial injury in a
      murine model using a magnetic resonance albumin-binding contrast agent.
AB  - BACKGROUND: Despite the beneficial effects of vascular interventions, these
      procedures may damage the endothelium leading to increased vascular permeability
      and remodeling. Re-endothelialization of the vessel wall, with functionally and
      structurally intact cells, is controlled by endothelial nitric oxide synthase
      (NOS3) and is crucial for attenuating adverse effects after injury. We
      investigated the applicability of the albumin-binding MR contrast agent,
      gadofosveset, to noninvasively monitor focal changes in vascular permeability and
      remodeling, after injury, in NOS3-knockout (NOS3(-/-)) and wild-type (WT) mice in
      vivo. METHODS AND RESULTS: WT and NOS3(-/-) mice were imaged at 7, 15, and 30
      days after aortic denudation or sham-surgery. T1 mapping (R1=1/T1, s(-1)) and
      delayed-enhanced MRI were used as measurements of vascular permeability (R1) and
      remodeling (vessel wall enhancement, mm(2)) after gadofosveset injection,
      respectively. Denudation resulted in higher vascular permeability and vessel wall
      enhancement 7 days after injury in both strains compared with sham-operated
      animals. However, impaired re-endothelialization and increased neovascularization
      in NOS3(-/-) mice resulted in significantly higher R1 at 15 and 30 days post
      injury compared with WT mice that showed re-endothelialization and lack of
      neovascularization (R1 [s(-1)]=15 days: NOS3 (-/-)4.02 [interquartile range, IQR,
      3.77-4.41] versus WT2.39 [IQR, 2.35-2.92]; 30 days: NOS3 (-/-)4.23 [IQR, 3.94
      4.68] versus WT2.64 [IQR, 2.33-2.80]). Similarly, vessel wall enhancement was
      higher in NOS3(-/-) but recovered in WT mice (area [mm(2)]=15 days: NOS3 (-/
      )5.20 [IQR, 4.68-6.80] versus WT2.13 [IQR, 0.97-3.31]; 30 days: NOS3 (-/-)7.35
      [IQR, 5.66-8.61] versus WT1.60 [IQR, 1.40-3.18]). Ex vivo histological studies
      corroborated the MRI findings. CONCLUSIONS: We demonstrate that increased
      vascular permeability and remodeling, after injury, can be assessed noninvasively
      using an albumin-binding MR contrast agent and may be used as surrogate markers
      for evaluating the healing response of the vessel wall after injury.

PMID- 25873721
TI  - Myocardial adaptation to high-intensity (interval) training in previously
      untrained men with a longitudinal cardiovascular magnetic resonance imaging study
      (Running Study and Heart Trial).
AB  - BACKGROUND: To prospectively evaluate whether short-term high-intensity
      (interval) training (HI(I)T) induces detectable morphological cardiac changes in
      previously untrained men in cardiovascular magnetic resonance imaging. METHODS
      AND RESULTS: Eighty-four untrained volunteers were randomly assigned to a HI(I)T
      group (n=42; 44.1+/-4.7 years) or an inactive control group (n=42; 42.3+/-5.6
      years). HI(I)T focused on interval runs (intensity: 95%-105% of individually
      calculated heart rate at the anaerobic threshold). Before and after 16 weeks, all
      subjects underwent physiological examination, stepwise treadmill test with blood
      lactate analysis, and contrast-enhanced cardiovascular magnetic resonance imaging
      (cine, tagging, and delayed enhancement). Indexed left ventricular (LV) and right
      ventricular (RV) volume (LV, 77.1+/-8.5-83.9+/-8.6; RV, 80.5+/-8.5-86.6+/-8.1)
      and mass (LV, 58.2+/-6.4-63.4+/-8.1; RV, 14.8+/-1.7-16.1+/-2.1) significantly
      increased with HI(I)T. Changes in LV and RV morphological parameters with HI(I)T
      were highly correlated with an increase in maximal aerobic capacity (VO2max) and
      a decrease in blood lactate concentration at the anaerobic threshold. Mean LV and
      RV remodeling index of HI(I)T group did not alter with training (0.76 +/-0.09 and
      0.24+/-0.10 g/mL, respectively [P=0.97 and P=0.72]), indicating balanced cardiac
      adaptation. Myocardial circumferential strain decreased after HI(I)T within all 6
      basal segments (anteroseptal, P=0.01 and anterolateral, P<0.001). There was no
      late gadolinium enhancement in any of the participants before or post HI(I)T.
      CONCLUSIONS: Sixteen weeks of HI(I)T lead to measurable changes in cardiac atrial
      and ventricular morphology and function in previously untrained men. This
      correlates with improvements in parameters of endurance capacity. CLINICAL TRIAL
      REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01406730.

PMID- 25873723
TI  - Longitudinal changes in left ventricular diastolic function in a general
      population.
AB  - BACKGROUND: Data on changes in left ventricular diastolic function (LVDF) over
      time in the general population are sparse. We, therefore, investigated in the
      population cohort clinical correlates of longitudinal changes in Doppler
      diastolic indexes analyzed as continuous measures and assessed factors predictive
      of the changes in LVDF grades over time. METHODS AND RESULTS: We measured early
      and late diastolic peak velocities of mitral inflow (E and A) by conventional
      Doppler, and the mitral annular velocities (e' and a') by tissue Doppler imaging
      in 650 participants (mean age, 50.7 years) at baseline and after 4.7 years (5th
      to 95th percentile, 3.7-5.4). In stepwise regression, the multivariable-adjusted
      correlates of the change in the transmitral and tissue Doppler imaging diastolic
      indexes included sex, age, baseline serum insulin, blood pressure, and heart
      rate. During follow-up, LVDF grades remained unchanged in 87.2% (95% confidence
      interval, 84.6%-89.8%), improved in 3.7% (95% confidence interval, 2.25%-5.15%),
      and worsened in 9.1% (95% confidence interval, 6.9%-11.3%). Baseline age was a
      strong predictor of worsening of LVDF from normal/mild grade to more advanced
      grade (odds ratio, 3.22; P<0.0001). A doubling of baseline insulin was associated
      with a 184% increase in the odds of worsening of LVDF (P<0.0001). Moreover,
      baseline diastolic blood pressure and the change in systolic blood pressure over
      time predicted worsening of LVDF (P<=0.014). CONCLUSIONS: The key findings of
      this study are that LVDF tended to worsen over time and was associated with
      advanced age, higher baseline insulin level, and hemodynamic parameters, such as
      heart rate and blood pressure.

PMID- 25873722
TI  - Multiparametric assessment of vascular function in peripheral artery disease:
      dynamic measurement of skeletal muscle perfusion, blood-oxygen-level dependent
      signal, and venous oxygen saturation.
AB  - BACKGROUND: Endothelial dysfunction present in patients with peripheral artery
      disease may be better understood by measuring the temporal dynamics of blood flow
      and oxygen saturation during reactive hyperemia than by conventional static
      measurements. METHODS AND RESULTS: Perfusion, Intravascular Venous Oxygen
      saturation, and T2* (PIVOT), a recently developed MRI technique, was used to
      measure the response to an ischemia-reperfusion paradigm in 96 patients with
      peripheral artery disease of varying severity and 10 healthy controls. Perfusion,
      venous oxygen saturation SvO2, and T2* were each quantified in the calf at 2-s
      temporal resolution, yielding a dynamic time course for each variable. Compared
      with healthy controls, patients had a blunted and delayed hyperemic response.
      Moreover, patients with lower ankle-brachial index had (1) a more delayed
      reactive hyperemia response time, manifesting as an increase in time to peak
      perfusion in the gastrocnemius, soleus, and peroneus muscles, and in the anterior
      compartment, (2) an increase in the time to peak T2* measured in the soleus
      muscle, and (3) a prolongation of the posterior tibial vein SvO2 washout time.
      Intrasession and intersession repeatability were also assessed. Results indicated
      that time to peak perfusion and time to peak T2* were the most reliable extracted
      time course metrics. CONCLUSIONS: Perfusion, dynamic SvO2, and T2* response times
      after induced ischemia are highly correlated with peripheral artery disease
      severity. Combined imaging of peripheral microvascular blood flow and dynamics of
      oxygen saturation with Perfusion, intravascular SvO2, and T2* may be a useful
      tool to investigate the pathophysiology of peripheral artery disease.

PMID- 25873724
TI  - Serial changes in diastolic function: lessons from the growing field of echo
      epidemiology.

PMID- 25873725
TI  - Novel magnetic resonance imaging end points for physiologic studies in peripheral
      arterial disease: elegance versus practicality.

PMID- 25873726
TI  - Early aortic transcatheter heart valve thrombosis: diagnostic value of contrast
      enhanced multidetector computed tomography.
AB  - BACKGROUND: Early stent valve thrombosis after transcatheter aortic valve
      implantation (TAVI) is a rare complication, which is diagnosed based on the
      appearance of clinical symptoms of heart failure and echocardiographic findings.
      After TAVI, transthoracic echocardiography is performed to assess transcatheter
      heart valve (THV) function. However, preliminary reports indicate the potential
      additive clinical value of multidetector computed tomography (MDCT) for the
      diagnosis of THV thrombosis. We sought to determine the value of MDCT for the
      diagnosis of THV thrombosis and the frequency of this complication after balloon
      expandable TAVI. METHODS AND RESULTS: MDCT was performed in 140 patients within 1
      to 3 months after TAVI with the Edwards Sapien XT THV to assess the presence of
      THV thrombosis and THV stent geometry. Post-TAVI MDCT identified THV thrombosis
      in 5 patients (4%). Of note, 4 of these patients were asymptomatic and had a
      normal transthoracic echocardiographic examination without signs of thrombus
      formation or flow obstruction. In patients with THV thrombosis, a left
      ventricular ejection fraction of <35% was present in 3 (60%), whereas 2 (40%) did
      not receive standard post-TAVI dual-antiplatelet therapy. Neither THV
      underexpansion nor THV noncircularity was detected in patients with THV
      thrombosis. CONCLUSIONS: Post-TAVI MDCT is a valuable tool for the diagnosis of
      THV thrombosis, and this complication seems to be more common than previously
      anticipated. Larger studies are required to identify specific risk factors of THV
      thrombosis.

PMID- 25873727
TI  - Treatment and clinical outcomes of transcatheter heart valve thrombosis.
AB  - BACKGROUND: Valve thrombosis has yet to be fully evaluated after transcatheter
      aortic valve implantation. This study aimed to report the prevalence, timing, and
      treatment of transcatheter heart valve (THV) thrombosis. METHODS AND RESULTS: THV
      thrombosis was defined as follows (1) THV dysfunction secondary to thrombosis
      diagnosed based on response to anticoagulation therapy, imaging modality or
      histopathology findings, or (2) mobile mass detected on THV suspicious of
      thrombus, irrespective of dysfunction and in absence of infection. Between
      January 2008 and September 2013, 26 (0.61%) THV thromboses were reported out of
      4266 patients undergoing transcatheter aortic valve implantation in 12 centers.
      Of the 26 cases detected, 20 were detected in the Edwards Sapien/Sapien XT cohort
      and 6 in the Medtronic CoreValve cohort. In patients diagnosed with THV
      thrombosis, the median time to THV thrombosis post-transcatheter aortic valve
      implantation was 181 days (interquartile range, 45-313). The most common clinical
      presentation was exertional dyspnea (n=17; 65%), whereas 8 (31%) patients had no
      worsening symptoms. Echocardiographic findings included a markedly elevated mean
      aortic valve pressure gradient (40.5+/-14.0 mm Hg), presence of thickened
      leaflets or thrombotic apposition of leaflets in 20 (77%) and a thrombotic mass
      on the leaflets in the remaining 6 (23%) patients. In 23 (88%) patients,
      anticoagulation resulted in a significant decrease of the aortic valve pressure
      gradient within 2 months. CONCLUSIONS: THV thrombosis is a rare phenomenon that
      was detected within the first 2 years after transcatheter aortic valve
      implantation and usually presented with dyspnea and increased gradients.
      Anticoagulation seems to have been effective and should be considered even in
      patients without visible thrombus on echocardiography.

PMID- 25873728
TI  - Prosthetic valve endocarditis after transcatheter aortic valve implantation.
AB  - BACKGROUND: Transcatheter aortic valve implantation (TAVI) is an advancing mode
      of treatment for inoperable or high-risk patients with aortic stenosis.
      Prosthetic valve endocarditis (PVE) after TAVI is a serious complication, but
      only limited data exist on its incidence, outcome, and procedural risk factors.
      METHODS AND RESULTS: Observational single-center study of 509 consecutive
      patients treated with a transcatheter implanted self-expandable aortic valve
      prosthesis (Medtronic CoreValve). We identified 18 patients diagnosed with TAVI
      PVE during a median follow-up period of 1.4 years (interquartile range, 0.5-2.5
      years; longest follow-up was 6.3 years). TAVI-PVE was most frequent in the first
      year after implantation (first-year incidence, 3.1% [confidence interval, 1.4%
      4.8%]); the overall annualized rate was 2.1% per patient-year (confidence
      interval, 1.2%-3.3%). Seventeen patients (94%) were treated conservatively and 1
      with surgery. Four patients (22%) died from endocarditis or complications to
      treatment, 2 of those (11%) during initial hospitalization for PVE. An increased
      risk of TAVI-PVE was seen in patients with low implanted valve position (hazard
      ratio, 2.8 [1.1-7.2]), moderate or worse postprocedural paravalvular
      regurgitation (hazard ratio, 4.0 [1.5-11]), implantation of >1 prosthesis (hazard
      ratio, 5.2 [1.5-18]), and any vascular complication (hazard ratio, 3.8 [1.5
      9.8]). CONCLUSIONS: TAVI-PVE occurred at a slightly higher rate than reported for
      surgically implanted valves. Conservative treatment was associated with an
      acceptable outcome. Suboptimal valve deployment and vascular complications were
      associated with an increased risk of TAVI-PVE.

PMID- 25873729
TI  - Activated clotting time and outcomes during percutaneous coronary intervention
      for non-ST-segment-elevation myocardial infarction: insights from the
      FUTURA/OASIS-8 Trial.
AB  - BACKGROUND: Activated clotting time (ACT) is widely used to guide unfractionated
      heparin dosing during percutaneous coronary intervention. However, its value in
      predicting complications is controversial in the modern era. We sought to examine
      the relationship between ACT and outcomes in non-ST-segment-elevation acute
      coronary syndrome patients. METHODS AND RESULTS: In the Fondaparinux With
      Unfractionated Heparin During Revascularization in Acute Coronary Syndromes
      (FUTURA/OASIS-8) trial, 2026 patients with non-ST-segment-elevation acute
      coronary syndrome treated with fondaparinux 2.5 mg/d and undergoing percutaneous
      coronary intervention were randomized to low-dose unfractionated heparin (50
      U/kg) or standard-dose unfractionated heparin (85 U/kg or 60 U/kg with
      glycoprotein IIb/IIIa inhibitors, with ACT guidance). No difference was shown for
      major bleeding and there was a trend toward a reduction in ischemic events with
      standard-dose unfractionated heparin. To clarify the additional value of ACT
      guidance, we analyzed with logistic modeling peri-percutaneous coronary
      intervention outcomes according to peak ACT as a linear function. A threshold
      effect was then investigated. No linear correlation was found between ACT and
      thrombotic or bleeding events. In patients not receiving planned glycoprotein
      IIb/IIIa inhibitors, a significant increase in rates of death, myocardial
      infarction, and target vessel revascularization was identified in patients with
      an ACT<=300 s (4.86% versus 2.78%; adjusted odds ratio, 1.84; 95% confidence
      interval, 1.06-3.21; P=0.03). No threshold was found for hemorrhagic
      complications in patients with or without glycoprotein IIb/IIIa inhibitors.
      CONCLUSIONS: Non-ST-segment-elevation acute coronary syndrome patients undergoing
      percutaneous coronary intervention with an ACT<=300 s are at increased risk of
      thrombotic complications. ACT, however, does not predict hemorrhagic
      complications. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov.
      Unique identifier: NCT00790907.

PMID- 25873730
TI  - Complete versus culprit-only revascularization for ST-segment-elevation
      myocardial infarction and multivessel disease: a meta-analysis and trial
      sequential analysis of randomized trials.
AB  - BACKGROUND: The 2013 American College of Cardiology Foundation/American Heart
      Association guidelines for patients with ST-segment-elevation myocardial
      infarction gives a class III indication for nonculprit artery percutaneous
      coronary intervention at the time of primary percutaneous coronary intervention,
      driven by data from observational studies. However, more recent trials suggest
      otherwise. METHODS AND RESULTS: We conducted PUBMED, EMBASE, and CENTRAL searches
      for randomized trials comparing complete versus culprit-only revascularization in
      patients with ST-segment-elevation myocardial infarction. Efficacy outcomes were
      major adverse cardiovascular events, as well as death, cardiovascular death,
      myocardial infarction, and repeat revascularization. Safety outcomes were
      contrast-induced nephropathy, contrast volume used, and procedure time. Five
      trials with 1165 patients fulfilled the inclusion criteria. Complete
      revascularization (68% during index percutaneous coronary intervention) was
      associated with significant reduction in major adverse cardiovascular events
      (rate ratio =0.48; 95% confidence interval =0.37-0.61), death (rate ratio =0.60;
      95% confidence interval =0.38-0.97), cardiovascular death (rate ratio =0.38, 95%
      confidence interval =0.20-0.73), and repeat revascularization (rate ratio =0.42;
      95% confidence interval =0.31-0.57) when compared with culprit-only
      revascularization. However, trial sequential analyses (similar to interim
      analysis of a randomized trial) powered for a 25% relative reduction showed firm
      evidence (cumulative z-curve crossed the monitoring boundary) only for major
      adverse cardiovascular events driven by a decrease in repeat revascularization
      with no firm evidence for reduction in death and myocardial infarction. Moreover,
      there was a significant increase in contrast volume use (mean difference 85.12
      [70.41-83.00] ml) and procedure time (mean difference 16.42 [13.22-19.63] mins)
      with complete revascularization without increase in contrast-induced nephropathy.
      CONCLUSIONS: In patients with ST-segment-elevation myocardial infarction,
      immediate or staged complete revascularization results in significant reduction
      in major adverse cardiovascular events driven largely by reduction in repeat
      revascularization with no firm evidence for the reduction in death or myocardial
      infarction when compared with culprit-only revascularization.

PMID- 25873731
TI  - Percutaneous tricuspid valve implantation: two-center experience with midterm
      results.
AB  - BACKGROUND: Severe tricuspid valve (TV) dysfunction may lead to surgical TV
      replacement with a biological valve prosthesis in patients with congenital heart
      disease. To expand the lifetime of this valve and reduce the number of surgeries,
      percutaneous TV implantation (PTVI) may be an effective alternative to repeated
      surgery. We report on our 2-center experience with PTVI. METHODS AND RESULTS:
      Between 2008 and 2014, 17 percutaneous valves were implanted in 16 patients with
      TV bioprosthesis dysfunction (9 females) from 2 centers. Median age and weight
      were 31.3 years (5-77.2) and 65.2 kg (17.7-107); 14 patients had congenital heart
      disease (univentricular heart with a right atrial to right ventricle
      bioprosthesis in 3, Ebstein's anomaly of the TV in 5, and other in 6), and 2 had
      acquired TV dysfunction. All procedures were successful (Melody n=7, Sapien 26 mm
      valve n=4, Sapien XT 29 mm valve n=6). One valve showed early dysfunction. It was
      replaced surgically and shortly after that a repeated PTVI was performed. The
      median duration of follow-up was 2.1 years (3 days to 6.3 years). The
      percutaneous valve was performing well in 15 of 16 patients. CONCLUSIONS: PTVI
      was safe and effectively improved TV function in all but 1 patient at midterm
      follow-up. We think that PTVI is a good alternative to repeated surgical TV
      replacements and that it may reduce the total number of open heart surgeries in
      these patients.

PMID- 25873732
TI  - Transcatheter aortic valve replacement failure: deja vu ou jamais vu?

PMID- 25873733
TI  - Activated clotting time during percutaneous coronary intervention: a test for all
      seasons or a mind tranquilizer?

PMID- 25873734
TI  - Minichromosome maintenance complex component 8 (MCM8) gene mutations result in
      primary gonadal failure.
AB  - BACKGROUND: Primary gonadal failure is characterised by primary amenorrhoea or
      early menopause in females, and oligospermia or azoospermia in males. Variants of
      the minichromosome maintenance complex component 8 gene (MCM8) have recently been
      shown to be significantly associated with women's menopausal age in genome-wide
      association studies. Furthermore, MCM8-knockout mice are sterile. The objective
      of this study was to elucidate the genetic aetiology of gonadal failure in two
      consanguineous families presenting as primary amenorrhoea in the females and as
      small testes and azoospermia in a male. METHODS AND RESULTS: Using whole exome
      sequencing, we identified two novel homozygous mutations in the MCM8 gene: a
      splice (c.1954-1G>A) and a frameshift (c.1469-1470insTA). In each consanguineous
      family the mutation segregated with the disease and both mutations were absent in
      100 ethnically matched controls. The splice mutation led to lack of the wild-type
      transcript and three different aberrant transcripts predicted to result in either
      truncated or significantly shorter proteins. Quantitative analysis of the
      aberrantly spliced transcripts showed a significant decrease in total MCM8
      message in affected homozygotes for the mutation, and an intermediate decrease in
      heterozygous family members. Chromosomal breakage following exposure to mitomcyin
      C was significantly increased in cells from homozygous individuals for c.1954
      1G>A, as well as c.1469-1470insTA. CONCLUSIONS: MCM8, a component of the pre
      replication complex, is crucial for gonadal development and maintenance in humans
      both males and females. These findings provide new insights into the genetic
      disorders of infertility and premature menopause in women.

PMID- 25873735
TI  - Nonsense mutation in the WDR73 gene is associated with Galloway-Mowat syndrome.
AB  - BACKGROUND: Neuroanatomical defects are often present in children with severe
      developmental delay and intellectual disabilities. Few genetic loci have been
      associated with disorders of neurodevelopment. Our objective of the present study
      was to analyse a consanguineous Arab family showing some of the hallmark signs of
      a rare cerebellar hypoplasia-related neurodevelopmental syndrome as a strategy
      for discovering a causative genetic mutation. METHODS: We used whole exome
      sequencing to identify the causative mutation in two female siblings of a
      consanguineous Arab family showing some of the hallmark signs of a cerebellar
      hypoplasia-related neurodevelopmental disorder. Direct Sanger sequencing was used
      to validate the candidate mutations that cosegregated with the phenotype. Gene
      expression and loss of function studies were carried out in the zebrafish model
      system to examine the role of the candidate gene in neurodevelopment. RESULTS:
      Patients presented with severe global developmental delay, intellectual
      disability, hypoplasia of the cerebellum and biochemical findings suggestive of
      nephrotic disease. Whole exome sequencing of the two patients revealed a shared
      nonsense homozygous variant in WDR73 (p.Q235X (c.703C>T)) resulting in loss of
      the last 144 amino acids of the protein. The variant segregated according to a
      recessive mode of inheritance in this family and was absent from public and our
      inhouse databases. We examined the developmental role of WDR73 using a loss-of
      function paradigm in zebrafish. There was a significant brain growth and
      morphogenesis defect in wdr73 knockdown embryos resulting in a poorly
      differentiated midbrain and cerebellum. CONCLUSIONS: The results provide new
      insight into the functional role of WDR73 in brain development and show that
      perturbation of its function in an inherited disorder in humans is associated
      with cerebellar hypoplasia as well as nephrotic disease, consistent with Galloway
      Mowat Syndrome.

PMID- 25873737
TI  - News feature: Capturing cancer's complexity.

PMID- 25873739
TI  - Reply to Gonsamo and Chen: Yield findings independent of cause of climate trends.

PMID- 25873740
TI  - Winter teleconnections can predict the ensuing summer European crop productivity.

PMID- 25873741
TI  - Pulmonary-Specific Intermountain Risk Score Predicts All-Cause Mortality via
      Spirometry, the Red Cell Distribution Width, and Other Laboratory Parameters.
AB  - BACKGROUND: Pulmonary function testing parameters predict cardiovascular and
      mortality outcomes. Previously, risk scores were created using the basic
      metabolic profile and complete blood count, including the Intermountain Risk
      Score (IMRS). This study sought to develop similar pulmonary-specific risk scores
      for mortality prediction. METHODS: Subjects evaluated by spirometry at 5
      Intermountain Healthcare hospitals (females: n = 2,943; males: n = 2,495) were
      randomly assigned to risk score derivation (70% of subjects) or an independent
      validation set (the remaining 30%). Sex-specific scores used spirometry, age, and
      metabolic and blood count laboratory data. Cox regression beta-coefficients
      formed the basis of risk score weightings. RESULTS: Among females, pulmonary IMRS
      was strongly associated with 5-y mortality in the validation set (hazard ratio =
      1.24 per +1 risk score, CI 1.16-1.33, P trend < .001), with C-statistics of C =
      0.835 and C = 0.757 for derivation and validation, respectively. Among males,
      validation results were similarly significant (hazard ratio = 1.20 per +1 risk
      score value, CI 1.11-1.28, P trend < .001), with C = 0.755 and C = 0.699 in
      derivation and validation sets, respectively. Results were stronger for pulmonary
      basic metabolic profile risk score, with females having C = 0.815 (derivation)
      and C = 0.806 (validation), whereas males had C = 0.734 and C = 0.731.
      CONCLUSIONS: Pulmonary-specific IMRS and pulmonary-specific basic metabolic
      profile risk score provided excellent discrimination of mortality among pulmonary
      subjects. These risk stratification tools combine familiar, relatively
      inexpensive, commonly-measured, standardized laboratory parameters with
      spirometry data. They may be electronically calculated and delivered at the point
      of care, providing meaningful risk information to assist clinicians in patient
      evaluations.

PMID- 25873736
TI  - CHRNA5 risk variant predicts delayed smoking cessation and earlier lung cancer
      diagnosis--a meta-analysis.
AB  - BACKGROUND: Recent meta-analyses show strong evidence of associations among
      genetic variants in CHRNA5 on chromosome 15q25, smoking quantity, and lung
      cancer. This meta-analysis tests whether the CHRNA5 variant rs16969968 predicts
      age of smoking cessation and age of lung cancer diagnosis. METHODS: Meta-analyses
      examined associations between rs16969968, age of quitting smoking, and age of
      lung cancer diagnosis in 24 studies of European ancestry (n = 29 072). In each
      dataset, we used Cox regression models to evaluate the association between
      rs16969968 and the two primary phenotypes (age of smoking cessation among ever
      smokers and age of lung cancer diagnosis among lung cancer case patients) and the
      secondary phenotype of smoking duration. Heterogeneity across studies was
      assessed with the Cochran Q test. All statistical tests were two-sided. RESULTS:
      The rs16969968 allele (A) was associated with a lower likelihood of smoking
      cessation (hazard ratio [HR] = 0.95, 95% confidence interval [CI] = 0.91 to 0.98,
      P = .0042), and the AA genotype was associated with a four-year delay in median
      age of quitting compared with the GG genotype. Among smokers with lung cancer
      diagnoses, the rs16969968 genotype (AA) was associated with a four-year earlier
      median age of diagnosis compared with the low-risk genotype (GG) (HR = 1.08, 95%
      CI = 1.04 to 1.12, P = 1.1*10(-5)). CONCLUSION: These data support the clinical
      significance of the CHRNA5 variant rs16969968. It predicts delayed smoking
      cessation and an earlier age of lung cancer diagnosis in this meta-analysis.
      Given the existing evidence that this CHRNA5 variant predicts favorable response
      to cessation pharmacotherapy, these findings underscore the potential clinical
      and public health importance of rs16969968 in CHRNA5 in relation to smoking
      cessation success and lung cancer risk.

PMID- 25873742
TI  - Effect of CPAP on Endothelial Function in Subjects With Obstructive Sleep Apnea:
      A Meta-Analysis.
AB  - Obstructive sleep apnea (OSA) is related to endothelial dysfunction. CPAP is the
      first-line treatment for OSA. We conducted a meta-analysis to evaluate the effect
      of CPAP on endothelial function in subjects with OSA. The PubMed, Embase, and
      Cochrane Library databases were searched. The overall effects were measured by
      the weighted mean difference with a 95% CI. Subgroup and meta-regression analyses
      were used to explore the sources of between-study heterogeneity. Eleven studies
      were eligible for the meta-analysis. A random-effects model revealed that CPAP
      significantly improved endothelial function as assessed by flow-mediated dilation
      (weighted mean difference of 2.92, 95% CI 2.21-3.63, P < .001), whereas there was
      no significant improvement in endothelial function in response to nitroglycerin
      mediated dilation (weighted mean difference of 0.90, 95% CI -1.63 to 3.43, P =
      .48). Age, sex, CPAP compliance and duration, and sleep-related variables had no
      effect on reduction in arterial stiffness after CPAP. Sensitivity analyses
      indicated that the protective effect of CPAP on endothelial function was robust.
      CPAP significantly improved flow-mediated dilation in subjects with OSA. Long
      term randomized controlled trials with larger sample sizes are needed to confirm
      the positive effect of CPAP on endothelial function in subjects with OSA. 

PMID- 25873743
TI  - Year in review 2014: asthma.
AB  - Asthma continues to be recognized as a well-known respiratory disease requiring
      complex management. Asthma is assessed and treated by clinicians across the
      continuum. The interest in evidence-based recommendations for diagnosis,
      treatment, and long-term management is ongoing and essential for aligning
      clinical practice with its changes. The purpose of this review is to provide
      updates from recent literature on asthma for clinicians. 

PMID- 25873744
TI  - COMETARY SCIENCE. The nonmagnetic nucleus of comet 67P/Churyumov-Gerasimenko.
AB  - Knowledge of the magnetization of planetary bodies constrains their origin and
      evolution, as well as the conditions in the solar nebular at that time. On the
      basis of magnetic field measurements during the descent and subsequent multiple
      touchdown of the Rosetta lander Philae on the comet 67P/Churyumov-Gerasimenko
      (67P), we show that no global magnetic field was detected within the limitations
      of analysis. The Rosetta Magnetometer and Plasma Monitor (ROMAP) suite of sensors
      measured an upper magnetic field magnitude of less than 2 nanotesla at the
      cometary surface at multiple locations, with the upper specific magnetic moment
      being <3.1 * 10(-5) ampere-square meters per kilogram for meter-size homogeneous
      magnetized boulders. The maximum dipole moment of 67P is 1.6 * 10(8) ampere
      square meters. We conclude that on the meter scale, magnetic alignment in the
      preplanetary nebula is of minor importance. 

PMID- 25873745
TI  - The appendix as a viable source of neural progenitor cells to functionally
      innervate bioengineered gastrointestinal smooth muscle tissues.
AB  - Appendix-derived neural progenitor cells (NPCs) have both neurogenic and
      gliogenic potential, but use of these cells for enteric neural cell therapy has
      not been addressed. The objective of this study was to determine whether NPCs
      obtained from the appendix would differentiate into enteric neural subsets
      capable of inducing neurotransmitter-mediated smooth muscle cell (SMC)
      contraction and relaxation. NPCs were isolated from the appendix and small
      intestine (SI) of rabbits. Bioengineered internal anal sphincter constructs were
      developed using the same source of smooth muscle and innervated with NPCs derived
      from either the appendix or SI. Innervated constructs were assessed for neuronal
      differentiation markers through Western blots and immunohistochemistry, and
      functionality was assessed through force-generation studies. Expression of neural
      and glial differentiation markers was observed in constructs containing appendix-
      and SI-derived NPCs. The addition of acetylcholine to both appendix and SI
      constructs caused a robust contraction that was decreased by pretreatment with
      the neural inhibitor tetrodotoxin (TTX). Electrical field stimulation caused
      relaxation of constructs that was completely abolished in the presence of TTX and
      significantly reduced on pretreatment with nitric oxide synthase inhibitor
      (Nomega-nitro-l-arginine methyl ester hydrochloride [l-NAME]). These data
      indicate that in the presence of identical soluble factors arising from
      intestinal SMCs, enteric NPCs derived from the appendix and SI differentiate in a
      similar manner and are capable of responding to physiological stimuli. This
      coculture paradigm could be used to explore the nature of the soluble factors
      derived from SMCs and NPCs in generating specific functional innervations.
      SIGNIFICANCE: This study demonstrates the ability of neural stem cells isolated
      from the appendix to differentiate into mature functional enteric neurons. The
      differentiation of neural stem cells from the appendix is similar to
      differentiation of neural stem cells derived from the gastrointestinal tract. The
      appendix is a vestigial organ that can be removed with minimal clinical
      consequence through laparoscopy. Results presented in this paper indicate that
      the appendix is a potential source of autologous neural stem cells required for
      cell therapy for the gastrointestinal tract.

PMID- 25873746
TI  - Productive Infection of Human Embryonic Stem Cell-Derived NKX2.1+ Respiratory
      Progenitors with Human Rhinovirus.
AB  - Airway epithelial cells generated from pluripotent stem cells (PSCs) represent a
      resource for research into a variety of human respiratory conditions, including
      those resulting from infection with common human pathogens. Using an NKX2.1-GFP
      reporter human embryonic stem cell line, we developed a serum-free protocol for
      the generation of NKX2.1(+) endoderm that, when transplanted into immunodeficient
      mice, matured into respiratory cell types identified by expression of CC10,
      MUC5AC, and surfactant proteins. Gene profiling experiments indicated that day 10
      NKX2.1(+) endoderm expressed markers indicative of early foregut but lacked genes
      associated with later stages of respiratory epithelial cell differentiation.
      Nevertheless, NKX2.1(+) endoderm supported the infection and replication of the
      common respiratory pathogen human rhinovirus HRV1b. Moreover, NKX2.1(+) endoderm
      upregulated expression of IL-6, IL-8, and IL-1B in response to infection, a
      characteristic of human airway epithelial cells. Our experiments provide proof of
      principle for the use of PSC-derived respiratory epithelial cells in the study of
      cell-virus interactions. SIGNIFICANCE: This report provides proof-of-principle
      experiments demonstrating, for the first time, that human respiratory progenitor
      cells derived from stem cells in the laboratory can be productively infected with
      human rhinovirus, the predominant cause of the common cold.

PMID- 25873747
TI  - Role of hepatocyte growth factor in the immunomodulation potential of amniotic
      fluid stem cells.
AB  - Human amniotic fluid stem cells (hAFSCs) may be useful for regenerative medicine
      because of their potential to differentiate into all three germ layers and to
      modulate immune response with different types of secretion molecules. This last
      issue has not been completely elucidated. The aim of this study was to
      investigate the secretome profile of the hAFSC, focusing on the role of
      hepatocyte growth factor (HGF) in immunoregulation through short and long
      cocultures with human peripheral blood mononuclear cells. We found that HGF
      produced by hAFSCs exerts a cytoprotective role, inducing an increase in caspase
      dependent apoptosis in human immune cells. This study provides evidence
      supporting the hypothesis that amniotic fluid is an ideal source of stem cells
      for expansion and banking properties for therapeutic use. hAFSCs not only are
      less immunogenic but also can secrete immunoregulatory factors that may be useful
      in autoimmune diseases or allogenic implants. SIGNIFICANCE: New information about
      the secretome pattern is reported in this paper. Human amniotic fluid stem cells
      (hAFSCs) possess immunomodulatory properties involving hepatocyte growth factor
      production. hAFSCs could be used in immunotherapies and might be able to avoid
      allogenic rejection.

PMID- 25873748
TI  - The diagnostic accuracy of HE4 in lung cancer: a meta-analysis.
AB  - The diagnostic value of serum HE4 in patients with lung cancer remains
      controversial. Thus, we performed a systematic review and meta-analysis to assess
      the diagnostic accuracy of serum HE4 for lung cancer. We conducted a
      comprehensive literature search in PubMed, EMBASE, Chinese National Knowledge
      Infrastructure (CNKI), and WANFANG databases between Jan. 1966 and Nov. 2014. The
      diagnostic sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR),
      negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and summary
      receiver operating characteristic curve (SROC) were pooled by Meta-DiSc 1.4
      software. A total of seven articles including 715 cases and 549 controls were
      included for analysis. The summary estimates for serum HE4 in the diagnosis of
      lung cancer in these studies were pooled SEN 0.72 (95% CI: 0.68-0.75), SPE 0.85
      (95% CI: 0.81-0.88), PLR 4.68 (95% CI: 3.23-6.78), NLR 0.31 (95% CI: 0.24-0.39),
      and DOR 17.14 (95% CI: 9.72-30.20), and the area under the curve (AUC) was
      0.8557. This meta-analysis indicated that serum HE4 is a potential tool in the
      diagnosis of lung cancer. In addition, considering the high heterogeneity and
      potential publication bias, further studies with rigorous design and large sample
      size are needed in the future. 

PMID- 25873749
TI  - Circulating soluble neuropilin-1 in patients with early cervical cancer and
      cervical intraepithelial neoplasia can be used as a valuable diagnostic
      biomarker.
AB  - OBJECTIVE: To investigate soluble neuropilin-1 (sNRP-1) in circulating and NRP-1
      protein in cervical tissues from patients with cervical cancer or cervical
      intraepithelial neoplasia (CIN). METHODS: sNRP-1 was measured in 64 preoperative
      patients and 20 controls. NRP-1 protein in cervical tissue was detected in 56
      patients and 20 controls. RESULTS: Both sNRP-1 and NRP-1 proteins were correlated
      with stage. sNRP-1 presented a high diagnostic ability of cervical cancer and
      CIN, with a sensitivity of 70.97% and a specificity of 73.68%. CONCLUSIONS: sNRP
      1 in circulating can serve as a possible valuable diagnostic biomarker for
      cervical cancer and CIN.

PMID- 25873750
TI  - Genetic basis for the lack of N-glycolylneuraminic acid expression in human
      tissues and its implication to human evolution.
AB  - Sialic acid is a family of acidic monosaccharides and consists of over 30
      derivatives. Two major derivatives are N-acetylneuraminic acid (NeuAc) and N
      glycolylneuraminic acid (NeuGc), and the hydroxylation of CMP-NeuAc is the rate
      limiting reaction for the production of NeuGc. The hydroxylation was carried out
      by a complex formed with hydroxylase, cytochrome b5, and NADH-cytochrome b5
      reductase. Mouse hydroxylase was purified from the cytosolic fraction of the
      liver and its cDNA was cloned. Normal human tissues do not contain NeuGc. Human
      hydroxylase cDNA was also cloned and the sequence revealed that human hydroxylase
      has 92 bp deletion. The deletion is the cause of defective expression of NeuGc in
      human. Chimpanzee has intact hydroxylase gene and the 92 bp deletion occurred
      after the divergence of human ancestor from chimpanzee ancestor. Biochemical and
      molecular biological studies on the biosynthesis of NeuGc and biological
      functions of NeuGc are reviewed. 

PMID- 25873752
TI  - The 1969-1985 Pozzuoli event and active volcanisms.
AB  - Pozzuoli is located at the center of the Campi Flegrei caldera, near Naples and
      is famous for its anomalous subsidence and upheaval documented since the Roman
      period. Its secular and gradual subsidence can be interpreted as self-loading
      compaction of the caldera fills while abrupt upheavals are geologically suspected
      to be caused by magmagenic movements or steam forces. In order to interpret the
      origin and the process of the Pozzuoli upheavals, they are compared with active
      volcanisms represented by the 1977-1982 eruption of Usu volcano in Hokkaido. Usu
      volcano outburst in 1977 in major pumice eruptions and repeated magmatic and
      phreatomagmatic eruptions, and manifested remarkable ground deformations
      accompanying earthquake swarms. In 1969, the ground of Pozzuoli began to upheave
      with increases in seismicity but finally failed to cause any eruptive phenomena
      at the surface; nevertheless there are common characteristics of their motives
      and processes between the two events. The motive of the Usu deformation is
      clearly due to magma movements while that of the Pozzuoli upheaval has not been
      completely settled. A quantitative relationship between seismicity and
      deformation gives a clue for discussing the motive of the Pozzuoli deformations.
      The discharge rates of seismic energy and the deformation rates are compared
      between the two events and a certain similarity is found. This suggests that the
      origin of the Pozzuoli event may be partly magmatic as well as the Usu eruption,
      but its behavior largely depends on the property of the caldera deposits. When
      their deformation volumes are taken into consideration, their characteristics
      become quantitatively conspicuous. The ground at Pozzuoli is much more easily
      deformed by the upward motive force than Usu volcano. This is due to the
      rheological property of the caldera deposits of Campi Flegrei, and agrees to the
      theory that interprets the secular subsidence observed in historical times, as
      self-loading compaction. It is interesting that there is a point of contact
      between anomalous movements of the ground along the seashore in Italy and
      remarkable magmatic movements at the active volcano in Japan. 

PMID- 25873753
TI  - Surgery for cystic pancreatic lesions in the post-sendai era: a single
      institution experience.
AB  - Introduction. The management of cystic pancreatic lesions has changed in recent
      years as a result of increasing knowledge of their biological behaviour, better
      diagnostic options, and international guidelines. Methods. Retrospective analysis
      of a cohort of 86 patients operated for cystic pancreatic lesions during a seven
      year period (2007-2014). Results. Final histopathology revealed 53 intraductal
      papillary mucinous neoplasms (19 branch duct IPMNs, 15 mixed type IPMNs, and 19
      main duct IPMNs), 14 serous and 13 mucinous cystic neoplasms, 3 solid
      pseudopapillary neoplasms, and 3 other lesions. 4 cases displayed high grade
      intraepithelial neoplasia and 2 cases displayed invasive cancer. A pylorus
      preserving partial duodenopancreatectomy was carried out in 27 patients, a total
      pancreatectomy was carried out in 9 patients, a left resection was carried out in
      42 patients, and segmental resections and enucleations were carried out in 4
      patients each. Overall postoperative morbidity and mortality were 40% and 2.3%,
      respectively. The preoperative diagnosis of a specific cystic tumor was accurate
      in 79% of patients and 9 patients (10%) could have avoided surgery with the
      correct preoperative diagnosis. Conclusion. Cystic pancreatic lesions are still a
      diagnostic challenge, requiring a dedicated multidisciplinary approach. The rate
      of malignancy is relatively small, whereas postoperative morbidity is
      substantial, underscoring the importance of adequate patient selection
      considering both the risk of surgery and the long term risk of malignancy. 

PMID- 25873751
TI  - AID to overcome the limitations of genomic information by introducing somatic DNA
      alterations.
AB  - The immune system has adopted somatic DNA alterations to overcome the limitations
      of the genomic information. Activation induced cytidine deaminase (AID) is an
      essential enzyme to regulate class switch recombination (CSR), somatic
      hypermutation (SHM) and gene conversion (GC) of the immunoglobulin gene. AID is
      known to be required for DNA cleavage of S regions in CSR and V regions in SHM.
      However, its molecular mechanism is a focus of extensive debate. RNA editing
      hypothesis postulates that AID edits yet unknown mRNA, to generate specific
      endonucleases for CSR and SHM. By contrast, DNA deamination hypothesis assumes
      that AID deaminates cytosine in DNA, followed by DNA cleavage by base excision
      repair enzymes. We summarize the basic knowledge for molecular mechanisms for CSR
      and SHM and then discuss the importance of AID not only in the immune regulation
      but also in the genome instability. 

PMID- 25873754
TI  - Improved fracture healing in patients with concomitant traumatic brain injury:
      proven or not?
AB  - Over the last 3 decades, scientific evidence advocates an association between
      traumatic brain injury (TBI) and accelerated fracture healing. Multiple clinical
      and preclinical studies have shown an enhanced callus formation and an increased
      callus volume in patients, respectively, rats with concomitant TBI. Over time,
      different substances (cytokines, hormones, etc.) were in focus to elucidate the
      relationship between TBI and fracture healing. Until now, the mechanism behind
      this relationship is not fully clarified and a consensus on which substance plays
      the key role could not be attained in the literature. In this review, we will
      give an overview of current concepts and opinions on this topic published in the
      last decade and both clinical and pathophysiological theories will be discussed. 

PMID- 25873755
TI  - Interleukin-18 increases TLR4 and mannose receptor expression and modulates
      cytokine production in human monocytes.
AB  - Interleukin-18 is a proinflammatory cytokine belonging to the interleukin-1
      family of cytokines. This cytokine exerts many unique biological and
      immunological effects. To explore the role of IL-18 in inflammatory innate immune
      responses, we investigated its impact on expression of two toll-like receptors
      (TLR2 and TLR4) and mannose receptor (MR) by human peripheral blood monocytes and
      its effect on TNF-alpha, IL-12, IL-15, and IL-10 production. Monocytes from
      healthy donors were stimulated or not with IL-18 for 18 h, and then the TLR2,
      TLR4, and MR expression and intracellular TNF-alpha, IL-12, and IL-10 production
      were assessed by flow cytometry and the levels of TNF-alpha, IL-12, IL-15, and IL
      10 in culture supernatants were measured by ELISA. IL-18 treatment was able to
      increase TLR4 and MR expression by monocytes. The production of TNF-alpha and IL
      10 was also increased by cytokine treatment. However, IL-18 was unable to induce
      neither IL-12 nor IL-15 production by these cells. Taken together, these results
      show an important role of IL-18 on the early phase of inflammatory response by
      promoting the expression of some pattern recognition receptors (PRRs) that are
      important during the microbe recognition phase and by inducing some important
      cytokines such as TNF-alpha and IL-10. 

PMID- 25873756
TI  - Fas/FasL pathway participates in regulation of antiviral and inflammatory
      response during mousepox infection of lungs.
AB  - Fas receptor-Fas ligand (FasL) signalling is involved in apoptosis of immune
      cells as well as of the virus infected target cells but increasing evidence
      accumulates on Fas as a mediator of apoptosis-independent processes such as
      induction of activating and proinflammatory signals. In this study, we examined
      the role of Fas/FasL pathway in inflammatory and antiviral response in lungs
      using a mousepox model applied to C57BL6/J, B6. MRL-Faslpr/J, and B6Smn.C3
      Faslgld/J mice. Ectromelia virus (ECTV) infection of Fas- and FasL-deficient mice
      led to increased virus titers in lungs and decreased migration of IFN-gamma
      expressing NK cells, CD4+ T cells, CD8+ T cells, and decreased IL-15 expression.
      The lungs of ECTV-infected Fas- and FasL-deficient mice showed significant
      inflammation during later phases of infection accompanied by decreased expression
      of anti-inflammatory IL-10 and TGF-beta1 cytokines and disturbances in CXCL1 and
      CXCL9 expression. Experiments in vitro demonstrated that ECTV-infected cultures
      of epithelial cells, but not macrophages, upregulate Fas and FasL and are
      susceptible to Fas-induced apoptosis. Our study demonstrates that Fas/FasL
      pathway during ECTV infection of the lungs plays an important role in controlling
      local inflammatory response and mounting of antiviral response. 

PMID- 25873757
TI  - Hydrogen-rich saline protects against ischemia/reperfusion injury in grafts after
      pancreas transplantations by reducing oxidative stress in rats.
AB  - PURPOSE: This study aimed to investigate the therapeutic potential of hydrogen
      rich saline on pancreatic ischemia/reperfusion (I/R) injury in rats. METHODS:
      Eighty heterotopic pancreas transplantations (HPT) were performed in syngenic
      rats. The receptors were randomized blindly into the following three groups: the
      HPT group and two groups that underwent transplantation and administration of
      hydrogen-rich saline (HS, >0.6 mM, 6 mL/kg) or normal saline (NS, 6 mL/kg) via
      the tail vein at the beginning of reperfusion (HPT + HS group, HPT + NS group).
      Samples from the pancreas and blood were taken at 12 hours after reperfusion. The
      protective effects of hydrogen-rich saline against I/R injury were evaluated by
      determining the changes in histopathology and measuring serological parameters,
      oxidative stress-associated molecules, and proinflammatory cytokines. RESULTS:
      Administration of hydrogen-rich saline produced notable protection against
      pancreatic I/R injury in rats. Histopathological improvements and recovery of
      impaired pancreatic function were observed. In addition, TNF-alpha, IL-1beta, and
      IL-6 were reduced markedly in the HPT + HS group. Additionally, there were
      noticeable inhibitory effects on the pancreatic malondialdehyde level and
      considerable recruitment of SOD and GPx, which are antioxidants. CONCLUSION:
      Hydrogen-rich saline treatment significantly attenuated the severity of
      pancreatic I/R injury in rats, possibly by reducing oxidative stress and
      inflammation.

PMID- 25873758
TI  - Pantoprazole decreases cell viability and function of human osteoclasts in vitro.
AB  - Proton pump inhibitors (PPIs) are commonly prescribed drugs that decrease stomach
      acidity and are thus often used to treat gastroesophageal reflux disease and as a
      preventative agent for the adverse effects of nonsteroidal anti-inflammatory
      drugs on the stomach mucosa. In recently published literature, an association
      between proton pump inhibitor administration and increased fracture risk has been
      stated. In order to reveal the underlying pathomechanisms of these observations,
      the effects of pantoprazole, a representative of the proton pump inhibitors, on
      human osteoclasts in vitro were evaluated in this study. Osteoclasts were
      stimulated with increasing concentrations of pantoprazole ranging from 0 MUg/mL
      to 10 MUg/mL over a period of seven days. Cell viability and tartrate-resistant
      acid phosphatase (TRAP) activity assays were performed after 1 day, 3 days, and 7
      days, respectively. Here, stimulated osteoclasts presented a significantly lower
      viability and TRAP activity than the negative controls. Osteoclast-specific gene
      expression was evaluated after seven days and revealed no significant differences
      between all samples. Overall, the bone degrading and resorptive function of
      osteoclasts is inhibited by the administration of proton pump inhibitors. While
      PPI-related fractures through "basic multicellular unit" dysfunction are
      unlikely, the underlying pathomechanism remains unknown. 

PMID- 25873759
TI  - Comment on "the effect of a community-based, primary health care exercise program
      on inflammatory biomarkers and hormone levels".

PMID- 25873760
TI  - Thiopurines induce oxidative stress in T-lymphocytes: a proteomic approach.
AB  - Thiopurines are extensively used immunosuppressants for the treatment of
      inflammatory bowel disease (IBD). The polymorphism of thiopurine S
      methyltransferase (TPMT) influences thiopurine metabolism and therapy outcome. We
      used a TPMT knockdown (kd) model of human Jurkat T-lymphocytes cells to study the
      effects of treatment with 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) on
      proteome and phosphoproteome. We identified thirteen proteins with altered
      expression and nine proteins with altered phosphorylation signals. Three proteins
      (THIO, TXD17, and GSTM3) with putative functions in cellular oxidative stress
      responses were altered by 6-TG treatment and another protein PRDX3 was
      differentially phosphorylated in TPMT kd cells. Furthermore, reactive oxygen
      species (ROS) assay results were consistent with a significant induction of
      oxidative stress by both TPMT knockdown and thiopurine treatments. Immunoblot
      analyses showed treatment altered expression of key antioxidant enzymes (i.e.,
      SOD2 and catalase) in both wt and kd groups, while SOD1 was downregulated by 6-TG
      treatment and TPMT knockdown. Collectively, increased oxidative stress might be a
      mechanism involved in thiopurine induced cytotoxicity and adverse effects (i.e.,
      hepatotoxicity) and an antioxidant cotherapy might help to combat this. Results
      highlight the significance of oxidative stress in thiopurines' actions and could
      have important implications for the treatment of IBD patients. 

PMID- 25873762
TI  - Immunology and infection by protozoan parasites.

PMID- 25873761
TI  - Effect of Helicobacter pylori eradication on TLR2 and TLR4 expression in patients
      with gastric lesions.
AB  - OBJECTIVE: Helicobacter pylori (Hp) is recognized by TLR4 and TLR2 receptors,
      which trigger the activation of genes involved in the host immune response. Thus,
      we evaluated the effect of eradication therapy on TLR2 and TLR4 mRNA and protein
      expression in H. pylori-infected chronic gastritis patients (CG-Hp+) and 3 months
      after treatment. METHODS: A total of 37 patients CG-Hp+ were evaluated. The
      relative quantification (RQ) of mRNA was assessed by TaqMan assay and protein
      expression by immunohistochemistry. RESULTS: Before treatment both TLR2 and TLR4
      mRNA in CG-Hp+ patients were slightly increased (TLR2 = 1.32; TLR4 = 1.26) in
      relation to Hp-negative normal gastric mucosa (P <= 0.05). After successful
      eradication therapy no significant change was observed (TLR2 = 1.47; TLR4 = 1.53;
      P > 0.05). In addition, the cagA and vacA bacterial genotypes did not influence
      the gene expression levels, and we observed a positive correlation between the RQ
      values of TLR2 and TLR4, both before and after treatment. Immunoexpression of the
      TLR2 and TLR4 proteins confirmed the gene expression results. CONCLUSION: In
      conclusion, the expression of both TLR2 and TLR4 is increased in CG-Hp+ patients
      regardless of cagA and vacA status and this expression pattern is not
      significantly changed after eradication of bacteria, at least for the short
      period of time evaluated.

PMID- 25873763
TI  - 5'-adenosine monophosphate-induced hypothermia attenuates brain
      ischemia/reperfusion injury in a rat model by inhibiting the inflammatory
      response.
AB  - Hypothermia treatment is a promising therapeutic strategy for brain injury. We
      previously demonstrated that 5'-adenosine monophosphate (5'-AMP), a ribonucleic
      acid nucleotide, produces reversible deep hypothermia in rats when the ambient
      temperature is appropriately controlled. Thus, we hypothesized that 5'-AMP
      induced hypothermia (AIH) may attenuate brain ischemia/reperfusion injury.
      Transient cerebral ischemia was induced by using the middle cerebral artery
      occlusion (MCAO) model in rats. Rats that underwent AIH treatment exhibited a
      significant reduction in neutrophil elastase infiltration into neuronal cells and
      matrix metalloproteinase 9 (MMP-9), interleukin-1 receptor (IL-1R), tumor
      necrosis factor receptor (TNFR), and Toll-like receptor (TLR) protein expression
      in the infarcted area compared to euthermic controls. AIH treatment also
      decreased the number of terminal deoxynucleotidyl transferase dUTP nick end
      labeling- (TUNEL-) positive neuronal cells. The overall infarct volume was
      significantly smaller in AIH-treated rats, and neurological function was
      improved. By contrast, rats with ischemic brain injury that were administered 5'
      AMP without inducing hypothermia had ischemia/reperfusion injuries similar to
      those in euthermic controls. Thus, the neuroprotective effects of AIH were
      primarily related to hypothermia. 

PMID- 25873764
TI  - Excessive daytime sleepiness is associated with changes in salivary inflammatory
      genes transcripts.
AB  - Excessive daytime sleepiness (EDS) is a ubiquitous problem that affects public
      health and safety. A test that can reliably identify individuals that suffer from
      EDS is needed. In contrast to other methods, salivary biomarkers are an
      objective, inexpensive, and noninvasive method to identify individuals with
      inadequate sleep. Although we have previously shown that inflammatory genes are
      elevated in saliva samples taken from sleep deprived individuals, it is unclear
      if inflammatory genes will be elevated in clinical populations with EDS. In this
      study, salivary samples from individuals with sleep apnea were evaluated using
      the Taqman low density inflammation array. Transcript levels for 3 genes,
      including prostaglandin-endoperoxide synthase 2 (PTGS2), were elevated in
      patients with sleep apnea. Interestingly, PTGS2 was also elevated in patients
      with EDS but who did not have sleep apnea. These data demonstrate the feasibility
      of using salivary transcript levels to identify individuals that self-report
      excessive daytime sleepiness. 

PMID- 25873765
TI  - Blockade of the JNK signalling as a rational therapeutic approach to modulate the
      early and late steps of the inflammatory cascade in polymicrobial sepsis.
AB  - Cecal ligation and puncture (CLP) is an experimental polymicrobial sepsis induced
      systemic inflammation that leads to acute organ failure. Aim of our study was to
      evaluate the effects of SP600125, a specific c-Jun NH2-terminal kinase (JNK)
      inhibitor, to modulate the early and late steps of the inflammatory cascade in a
      murine model of CLP-induced sepsis. CB57BL/6J mice were subjected to CLP or sham
      operation. Animals were randomized to receive either SP600125 (15 mg/kg) or its
      vehicle intraperitoneally 1 hour after surgery and repeat treatment every 24
      hours. To evaluate survival, a group of animals was monitored every 24 hours for
      120 hours. Two other animals were sacrificed 4 or 18 hours after surgical
      procedures; lung and liver samples were collected for biomolecular and
      histopathologic analysis. The expression of p-JNK, p-ERK, TNF-alpha, HMGB-1, NF
      kappaB, Ras, Rho, Caspase 3, Bcl-2, and Bax was evaluated in lung and liver
      samples; SP600125 improved survival, reduced CLP induced activation of JNK, NF
      kappaB, TNF-alpha, and HMGB-1, inhibited proapoptotic pathway, preserved Bcl-2
      expression, and reduced histologic damage in both lung and liver of septic mice.
      SP600125 protects against CLP induced sepsis by blocking JNK signalling;
      therefore, it can be considered a therapeutic approach in human sepsis. 

PMID- 25873766
TI  - Toll-like receptor-4 mediated inflammation is involved in the cardiometabolic
      alterations induced by intermittent hypoxia.
AB  - OBJECTIVE: Intermittent hypoxia (IH) is a major component of sleep apnea syndrome
      as its cardiometabolic complications have been mainly attributed to IH. The
      pathophysiology is still poorly understood but there are some similarities with
      the obesity-associated cardiometabolic complications. As the latter results from
      inflammation involving toll-like receptor-4 (TLR4) signaling, we assessed this
      pathway in the cardiometabolic consequences of IH. METHODS: Lean adult male TLR4
      deficient (TLR4(-/-)) mice and their controls (C57BL/6 mice) were exposed to
      either IH (FiO2 21-5%, 1 min cycle, 8 h/day) or air (normoxic mice) for 4 weeks.
      Animals were assessed at 1-week exposure for insulin tolerance test and after 4
      week exposure for morphological and inflammatory changes of the epididymal fat
      and thoracic aorta. RESULTS: IH induced insulin resistance, morphological and
      inflammatory changes of the epididymal fat (smaller pads and adipocytes, higher
      release of TNF-alpha and IL-6) and aorta (larger intima-media thickness and
      higher NFkappaB-p50 activity). All these alterations were prevented by TLR4
      deletion. CONCLUSION: IH induces metabolic and vascular alterations that involve
      TLR4 mediated inflammation. These results confirm the important role of
      inflammation in the cardiometabolic consequences of IH and suggest that targeting
      TLR4/NFkappaB pathway could represent a further therapeutic option for sleep
      apnea patients.

PMID- 25873767
TI  - Relationship between gingival inflammation and pregnancy.
AB  - An increase in the prevalence and severity of gingival inflammation during
      pregnancy has been reported since the 1960s. Though the etiology is not fully
      known, it is believed that increasing plasma sex steroid hormone levels during
      pregnancy have a dramatic effect on the periodontium. Current works of research
      have shown that estrogen and progesterone increasing during pregnancy are
      supposed to be responsible for gingivitis progression. This review is focused not
      only on epidemiological studies, but also on the effects of progesterone and
      estrogen on the change of subgingival microbiota and immunologic physiological
      mediators in periodontal tissue (gingiva and periodontal ligament), which
      provides current information about the effects of pregnancy on gingival
      inflammation. 

PMID- 25873769
TI  - Inflammatory and antioxidant pattern unbalance in "clopidogrel-resistant"
      patients during acute coronary syndrome.
AB  - BACKGROUND: In acute coronary syndrome (ACS), inflammation and redox response are
      associated with increased residual platelet reactivity (RPR) on clopidogrel
      therapy. We investigated whether clopidogrel interaction affects platelet
      function and modulates factors related to inflammation and oxidation in ACS
      patients differently responding to clopidogrel. MATERIAL AND METHODS: Platelet
      aggregation was measured in 29 ACS patients on dual (aspirin/clopidogrel)
      antiplatelet therapy. Nonresponders (NR) were defined as RPR >=70% by ADP.
      Several inflammatory and redox parameters were assayed and platelet proteome was
      determined. RESULTS: Eight (28%) out of 29 ACS patients resulted NR to
      clopidogrel. At 24 hours, the levels of Th2-type cytokines IL-4, IFNgamma, and
      MCP-1 were higher in NR, while blood GSH (r-GSHbl) levels were lower in NR than
      responders (R). Proteomic analysis evidenced an upregulated level of platelet
      adhesion molecule, CD226, and a downregulation of the antioxidant peroxiredoxin
      4. In R patients the proinflammatory cytokine IL-6 decreased, while the anti
      inflammatory cytokine IL-1Ra increased. CONCLUSIONS: In patients with high RPR on
      clopidogrel therapy, an unbalance of inflammatory factors, platelet adhesion
      molecules, and circulatory and platelet antioxidant molecules was observed during
      the acute phase. Proinflammatory milieu persists in nonresponders for a long time
      after the acute event while antioxidant blood factors tend to conform to normal
      responsiveness.

PMID- 25873768
TI  - Contribution of microglia-mediated neuroinflammation to retinal degenerative
      diseases.
AB  - Retinal degenerative diseases are major causes of vision loss and blindness
      worldwide and are characterized by chronic and progressive neuronal loss. One
      common feature of retinal degenerative diseases and brain neurodegenerative
      diseases is chronic neuroinflammation. There is growing evidence that retinal
      microglia, as in the brain, become activated in the course of retinal
      degenerative diseases, having a pivotal role in the initiation and propagation of
      the neurodegenerative process. A better understanding of the events elicited and
      mediated by retinal microglia will contribute to the clarification of disease
      etiology and might open new avenues for potential therapeutic interventions. This
      review aims at giving an overview of the roles of microglia-mediated
      neuroinflammation in major retinal degenerative diseases like glaucoma, age
      related macular degeneration, and diabetic retinopathy. 

PMID- 25873770
TI  - Acute necrotizing encephalopathy: an underrecognized clinicoradiologic disorder.
AB  - Acute necrotizing encephalopathy (ANE) is a rare but distinctive type of acute
      encephalopathy with global distribution. Occurrence of ANE is usually preceded by
      a virus-associated febrile illness and ensued by rapid deterioration. However,
      the causal relationship between viral infections and ANE and the exact
      pathogenesis of ANE remain unclear; both environmental and host factors might be
      involved. Most cases of ANE are sporadic and nonrecurrent, namely, isolated or
      sporadic ANE; however, few cases are recurrent and with familial episodes. The
      recurrent and familial forms of ANE were found to be incompletely autosomal
      dominant. Further the missense mutations in the gene encoding the nuclear pore
      protein Ran Binding Protein 2 (RANBP2) were identified. Although the clinical
      course and the prognosis of ANE are diverse, the hallmark of neuroradiologic
      manifestation of ANE is multifocal symmetric brain lesions which are demonstrated
      by computed tomography (CT) or magnetic resonance imaging (MRI). The treatment of
      ANE is still under investigation. We summarize the up-to-date knowledge on ANE,
      with emphasis on prompt diagnosis and better treatment of this rare but fatal
      disease. 

PMID- 25873771
TI  - Infliximab preferentially induces clinical remission and mucosal healing in short
      course Crohn's disease with luminal lesions through balancing abnormal immune
      response in gut mucosa.
AB  - This study was undertaken to evaluate the efficacy of infliximab (IFX) in
      treatment of Crohn's disease (CD) patients. 106 CD patients were undergoing
      treatment with IFX from five hospitals in Shanghai, China. Clinical remission to
      IFX induction therapy was defined as Crohn's disease activity index (CDAI) < 150.
      Clinical response was assessed by a decrease in CDAI >= 70, and the failure as a
      CDAI was not significantly changed or increased. Ten weeks after therapy, 61
      (57.5%) patients achieved clinical remission, 17 (16.0%) had clinical response,
      and the remaining 28 (26.4%) were failed. In remission group, significant changes
      were observed in CDAI, the Simple Endoscopic Score for Crohn's Disease (SES-CD),
      and serum indexes. Patients with short disease duration (22.2 +/- 23.2 months)
      and luminal lesions showed better effects compared to those with long disease
      duration (71.0 +/- 58.2 months) or stricturing and penetrating lesions. IFX
      markedly downregulated Th1/Th17-mediated immune response but promoted IL-25
      production in intestinal mucosa from remission group. No serious adverse events
      occurred to terminate treatment. Taken together, our studies demonstrated that
      IFX is efficacious and safe in inducing clinical remission, promoting mucosal
      healing, and downregulating Th1/Th17-mediated immune response in short course CD
      patients with luminal lesions. 

PMID- 25873772
TI  - Role of IL-38 and its related cytokines in inflammation.
AB  - Interleukin- (IL-) 38 is a recently discovered cytokine and is the tenth member
      of the IL-1 cytokine family. IL-38 shares structural features with IL-1 receptor
      antagonist (IL-1Ra) and IL-36Ra. IL-36R is the specific receptor of IL-38, a
      partial receptor antagonist of IL-36. IL-38 inhibits the production of T-cell
      cytokines IL-17 and IL-22. IL-38 also inhibits the production of IL-8 induced by
      IL-36gamma, thus inhibiting inflammatory responses. IL-38-related cytokines,
      including IL-1Ra and IL-36Ra, are involved in the regulation of inflammation and
      immune responses. The study of IL-38 and IL-38-related cytokines might provide
      new insights for developing anti-inflammatory treatments in the near future. 

PMID- 25873773
TI  - OSAS-related inflammatory mechanisms of liver injury in nonalcoholic fatty liver
      disease.
AB  - Obstructive sleep apnoea syndrome (OSAS) is a common sleep disorder, affecting
      over 4% of the general population, and is associated with metabolic syndrome and
      cardiovascular disease, independent of obesity and traditional risk factors. OSAS
      has been recently connected to nonalcoholic fatty liver disease (NAFLD), the most
      common chronic liver disease in the world, which can be found in 30% of the
      general adult population. Several studies suggest that the chronic intermittent
      hypoxia (CIH) of OSAS patients may per se trigger liver injury, inflammation, and
      fibrogenesis, promoting NAFLD development and the progression from steatosis to
      steatohepatitis, cirrhosis, and hepatocellular carcinoma. In NAFLD patients,
      liver disease may be caused by hypoxia both indirectly by promoting inflammation
      and insulin resistance and directly by enhancing proinflammatory cytokine
      production and metabolic dysregulation in liver cells. In this review, we focus
      on molecular mechanisms linking OSAS to NAFLD, including hypoxia inducible factor
      (HIF), nuclear factor kappa B (NF-kappaB), YKL-40, unfolded protein response, and
      hypoxic adipose tissue inflammation, which all could provide novel potential
      therapeutic approaches for the management of NAFLD patients with OSAS. 

PMID- 25873775
TI  - Methadone-Associated Prolongation of the QTc Interval at Doses Used for Chronic
      Pain.
AB  - PURPOSE: Methadone HCl is used for the management of opioid addiction and chronic
      pain. Published reports indicate that methadone can be associated with a
      prolonged corrected QT (QTc) interval, especially at daily doses greater than 100
      mg. The risk of this adverse effect is not always considered by health care pain
      specialists, who sometimes use lower doses. The objectives of this case series
      were to evaluate the effects of methadone on the QTc interval in patients being
      treated for chronic pain and to determine whether there was a correlation between
      dosing and the degree of QTc prolongation. METHODS: A computerized list was
      generated for patients who had active methadone prescriptions between December
      2007 and November 2008. We performed a retrospective chart review to evaluate
      methadone dosing, potential drug interactions, electrocardiograms (ECGs), and the
      QTc interval. An emphasis was placed on patients with QTc intervals greater than
      500 milliseconds (msec). RESULTS: Of the 51 patients reviewed, seven had QTc
      intervals greater than 500 msec. Methadone doses ranged from 5 to 180 mg/day;
      three patients received daily doses greater than 100 mg. Six of the seven
      patients were taking at least one other drug that had the ability to prolong the
      QTc interval. CONCLUSION: Our case series suggested that QTc intervals should be
      routinely monitored in patients receiving methadone and that patients should be
      screened before therapy is initiated. Ideally, the QTc interval should be
      monitored before treatment begins and during repeated intervals thereafter. On
      the basis of the analysis, a protocol was developed at our facility for
      monitoring ECGs in patients being treated with methadone for chronic pain.

PMID- 25873776
TI  - Pharmaceutical approval update.
AB  - Nivolumab (Opdivo) for unresectable or metastatic melanoma;
      ombitasvir/paritaprevir/ritonavir with dasabuvir (Viekira Pak) for hepatitis C
      virus infection; and olaparib (Lynparza) for ovarian cancer. 

PMID- 25873774
TI  - The role of the immune system in triplet repeat expansion diseases.
AB  - Trinucleotide repeat expansion disorders (TREDs) are a group of dominantly
      inherited neurological diseases caused by the expansion of unstable repeats in
      specific regions of the associated genes. Expansion of CAG repeat tracts in
      translated regions of the respective genes results in polyglutamine- (polyQ-)
      rich proteins that form intracellular aggregates that affect numerous cellular
      activities. Recent evidence suggests the involvement of an RNA toxicity component
      in polyQ expansion disorders, thus increasing the complexity of the pathogenic
      processes. Neurodegeneration, accompanied by reactive gliosis and astrocytosis is
      the common feature of most TREDs, which may suggest involvement of inflammation
      in pathogenesis. Indeed, a number of immune response markers have been observed
      in the blood and CNS of patients and mouse models, and the activation of these
      markers was even observed in the premanifest stage of the disease. Although
      inflammation is not an initiating factor of TREDs, growing evidence indicates
      that inflammatory responses involving astrocytes, microglia, and the peripheral
      immune system may contribute to disease progression. Herein, we review the
      involvement of the immune system in the pathogenesis of triplet repeat expansion
      diseases, with particular emphasis on polyglutamine disorders. We also present
      various therapeutic approaches targeting the dysregulated inflammation pathways
      in these diseases. 

PMID- 25873777
TI  - MiRNA-21 promotes fibrosis in orbital fibroblasts from thyroid-associated
      ophthalmopathy.
AB  - PURPOSE: This study aimed to determine the role of miR-21 in orbital fibroblasts
      obtained from donors with thyroid-associated ophthalmopathy (TAO) and to
      elucidate the regulation of fibrosis by miR-21 in the pathological process of
      TAO. METHODS: The expression of miR-21 was investigated in orbital tissues from
      26 donors with TAO and 10 donors without TAO. Human orbital fibroblasts were
      cultivated from TAO donors, and the role of miR-21 in orbital fibroblast
      proliferation, apoptosis, and differentiation was analyzed. Moreover, the effect
      of transforming growth factor-beta1 (TGF-beta1) on miR-21 expression was also
      analyzed. In addition, the regulation of miR-21 in TGF-beta1-induced collagen
      production was determined. RESULTS: The expression of miR-21 in orbital
      fibroblasts from TAO was higher than in donors without TAO. Additional
      experiments demonstrated that miR-21 enhanced proliferation, decreased apoptosis,
      and promoted differentiation in TAO orbital fibroblasts. Moreover, this study
      also showed that TGF-beta1 induced miR-21 expression in a time- and dose
      dependent manner and miR-21 promoted collagen I mRNA expression and total
      collagen production induced by TGF-beta1. Additionally, miR-21 activated the TGF
      beta1/Smad signaling pathway by enhancing Smad3 phosphorylation. CONCLUSIONS: The
      present study shows that miR-21 regulates cell proliferation, apoptosis, and
      differentiation in orbital fibroblasts from TAO, and acts as a mediator in TGF
      beta1-induced collagen production. These data predict a close association between
      miR-21 and orbital muscle fibrosis, and provide a novel therapeutic target for
      TAO.

PMID- 25873779
TI  - Understanding Regeneration of Arsenate-Loaded Ferric Hydroxide-Based Adsorbents.
AB  - Adsorbents comprising ferric hydroxide loaded on a variety of support materials
      are commonly used to remove arsenic from potable water. Although several studies
      have investigated the effects of support properties on arsenic adsorption, there
      have been no investigations of their effects on adsorbent regeneration.
      Furthermore, the effect of regenerant solution composition and the kinetics of
      regeneration have not been investigated. This research investigated the effects
      of adsorbent and regenerant solution properties on the kinetics and efficiency of
      regeneration of arsenate-loaded ferric hydroxide-based adsorbents. Solutions
      containing only 0.10-5.0 M NaOH or 0.10-1.0 M NaCl, as well as solutions
      containing both compounds, were used as regenerants. On all media, >99% of
      arsenate was adsorbed through complexation with ferric hydroxide. Arsenate
      recovery was controlled by both equilibrium and kinetic limitations. Adsorbents
      containing support material with weak base anion-exchange functionality or no
      anion-exchange functionality could be regenerated with NaOH solutions alone.
      Regeneration of media containing strong base anion (SBA)-exchange functionality
      was greatly enhanced by addition of 0.10 M NaCl to the NaOH regenerant solutions.
      Adsorbed silica had a significant effect on NaOH regeneration of media containing
      type I SBA-exchange functionality, but on other media, adsorbed silica had little
      impact on regeneration. On all media, 5-25% of arsenate was resistant to
      desorption in 1.0 M NaOH solutions. However, the use of 2.5-5.0 M NaOH solutions
      significantly reduced the desorption-resistant fraction.

PMID- 25873778
TI  - XRCC1 and XPD genetic polymorphisms and susceptibility to age-related cataract: a
      meta-analysis.
AB  - OBJECTIVE: This meta-analysis aimed to determine the relationships between XRCC1
      Arg399Gln (rs25487 G>A) and XPD Lys751Gln (rs1052559 A>C) polymorphisms and
      susceptibility to age-related cataract. METHODS: Medline (1966-2013), the
      Cochrane Library Database (Issue 12, 2013), EMBASE (1980-2013), CINAHL (1982
      2013), Web of Science (1945-2013) and the Chinese Biomedical Database (CBM; 1982
      2013) were searched without language restrictions. Various combinations of the
      keywords and MeSH terms were used to screen for potentially relevant studies,
      specifically "genetic polymorphisms" or "SNPs" or "variation" or "single
      nucleotide polymorphism" or "polymorphism" or "mutation" or "variant"; "X-ray
      repair cross complementing protein 1" or "Xeroderma Pigmentosum Group D Protein"
      or "X-ray repair cross complementing protein 1" or "Xeroderma Pigmentosum Group D
      Protein" or "XPD" or "Xeroderma Pigmentosum Complementation Group D Protein" or
      "ERCC2" or "XRCC1" or "XRCC1 DNA repair protein"; and "Cataract" or " Membranous
      Cataract" or " Pseudoaphakia." Meta-analyses were conducted using Stata 12.0
      software. Crude odds ratios (ORs) and their corresponding 95% confidence
      intervals (95% CI) were calculated. RESULTS: Six independent case-control studies
      were included in the meta-analysis. Our results indicated that the association
      between the genetic polymorphisms of XRCC1 Arg399Gln G>A and XPD Lys751Gln A>C
      and increased susceptibility to age-related cataracts was statistically
      significant (XRCC1 Arg399Gln: OR=1.30, 95% CI=1.17-1.44, p<0.001; XPD Lys751Gln:
      OR=1.25, 95% CI=1.12-1.40, p<0.001, respectively). Ethnicity-stratified analysis
      indicated that the XRCC1 Arg399Gln G>A polymorphism was correlated with the
      development and progression of age-related cataract in China, India, and Turkey
      in the allele model and the dominant model. For the XPD Lys751Gln A>C variant,
      the association with the pathogenesis of age-related cataract in China and Turkey
      in the allele model and the dominant model was investigated. CONCLUSIONS: The
      association of XRCC1 Arg399Gln and XPD Lys751Gln polymorphisms with age-related
      cataract susceptibility observed in our meta-analyses supports the view that
      XRCC1 and XPD may play important roles in susceptibility to age-related cataract.

PMID- 25873780
TI  - Muscle fatigue, nNOS and muscle fiber atrophy in limb girdle muscular dystrophy.
AB  - Muscle fatigability and atrophy are frequent clinical signs in limb girdle
      muscular dystrophy (LGMD), but their pathogenetic mechanisms are still poorly
      understood. We review a series of different factors that may be connected in
      causing fatigue and atrophy, particularly considering the role of neuronal nitric
      oxide synthase (nNOS) and additional factors such as gender in different forms of
      LGMD (both recessive and dominant) underlying different pathogenetic mechanisms.
      In sarcoglycanopathies, the sarcolemmal nNOS reactivity varied from absent to
      reduced, depending on the residual level of sarcoglycan complex: in cases with
      complete sarcoglycan complex deficiency (mostly in beta-sarcoglycanopathy), the
      sarcolemmal nNOS reaction was absent and it was always associated with early
      severe clinical phenotype and cardiomyopathy. Calpainopathy, dysferlinopathy, and
      caveolinopathy present gradual onset of fatigability and had normal sarcolemmal
      nNOS reactivity. Notably, as compared with caveolinopathy and
      sarcoglycanopathies, calpainopathy and dysferlinopathy showed a higher degree of
      muscle fiber atrophy. Males with calpainopathy and dysferlinopathy showed
      significantly higher fiber atrophy than control males, whereas female patients
      have similar values than female controls, suggesting a gender difference in
      muscle fiber atrophy with a relative protection in females. In female patients,
      the smaller initial muscle fiber size associated to endocrine factors and less
      physical effort might attenuate gender-specific muscle loss and atrophy. 

PMID- 25873781
TI  - The effect of atrial preference pacing on atrial fibrillation
      electrophysiological substrate in Myotonic Dystrophy type 1 population.
AB  - P-wave dispersion is a non invasive indicator of intra-atrial conduction
      heterogeneity producing substrate for reentry, which is a pathophysiological
      mechanism of atrial fibrillation. The relationship between P-wave dispersion (PD)
      and atrial fibrillation (AF) in Myotonic dystrophy type 1 (DM1) patients is still
      unclear. Atrial Preference Pacing (APP) is an efficient algorithm to prevent
      paroxysmal AF in patients implanted with dual-chamber pacemaker. Aim of our study
      was to evaluate the possible correlation between atrial preference pacing
      algorithm, P-wave dispersion and AF burden in DM1 patients with normal cardiac
      function underwent permanent dual-chamber pacemaker implantation. We enrolled 50
      patients with DM1 (age 50.3 +/- 7.3; 11 F) underwent dual-chamber pacemaker
      implantation for various degree of atrioventricula block. The study population
      was randomized following 1 months stabilization period to APP algorithm features
      programmed OFF or ON. Patients were assessed every 3 months for the first year,
      and every 6 months thereafter up to 3 years. At each follow-up visit, we counted:
      the number of premature atrial beats, the number and the mean duration of AF
      episodes, AF burden and the percentage of atrial and ventricular pacing. APP ON
      Group showed lower number of AF episodes (117 +/- 25 vs. 143 +/- 37; p = 0.03)
      and AF burden (3059 +/- 275 vs. 9010 +/- 630 min; p < 0.04) than APP OFF Group.
      Atrial premature beats count (44903 +/- 30689 vs. 13720 +/- 7717 beats; p =
      0.005) and Pwave dispersion values (42,1 +/- 11 ms vs. 29,1 +/- 4,2 ms, p =
      0,003) were decreased in APP ON Group. We found a significant positive
      correlation between PD and AF burden (R = 0,8, p = 0.007). Atrial preference
      pacing algorithm, decreasing the number of atrial premature beats and the P-wave
      dispersion, reduces the onset and perpetuator factors of AF episodes and
      decreases the AF burden in DM1 patients underwent dual chamber pacemaker
      implantation for various degree of atrioventricular blocks and documented atrial
      fibrillation. 

PMID- 25873782
TI  - Psychological and practical difficulties among parents and healthy siblings of
      children with Duchenne vs. Becker muscular dystrophy: an Italian comparative
      study.
AB  - This study explored the burden in parents and healthy siblings of 4-17 year-old
      patients with Duchenne (DMD) and Becker (BMD) muscular dystrophies, and whether
      the burden varied according to clinical aspects and social resources. Data on
      socio-demographic characteristics, patient's clinical history, parent and healthy
      children burden, and on parent's social resources were collected using self
      reported questionnaires administered to 336 parents of patients with DMD (246)
      and BMD (90). Parents of patients with DMD reported higher burden than those of
      patients with BMD, especially concerning feeling of loss (84.3% DMD vs. 57.4%
      BMD), stigma (44.2% DMD vs. 5.5% BMD) and neglect of hobbies (69.0% DMD vs. 32.5%
      BMD). Despite the burden, 66% DMD and 62.4% BMD parents stated the caregiving
      experience had a positive impact on their lives. A minority of parents believed
      MD has a negative influence on the psychological well-being (31.0% DMD vs. 12.8%
      BMD), and social life of unaffected children (25.7% vs. 18.4%). In the DMD group,
      burden correlated with duration of illness and parent age, and burden was higher
      among parents with lower social contacts and support in emergencies. In DMD,
      difficulties among healthy children were reported as higher by parents who were
      older, had higher burden and lower social contacts. In both groups, burden
      increased in relation to patient disability. These findings underline that the
      psychological support to be provided to parents of patients with MD, should take
      into account clinical features of the disease. 

PMID- 25873783
TI  - Charcot-Marie-Tooth 4B2 caused by a novel mutation in the MTMR13/SBF2 gene in two
      related Portuguese families.
AB  - INTRODUCTION: CMT4B2 is a rare subtype of CMT caused by pathogenic mutations in
      the myotubularin-related protein-13/set binding factor 2 (MTMR13/SBF2) gene.
      Nerve conduction velocities are markedly reduced and focally folded myelin
      sheaths are present on nerve biopsies. We presented two patients from two related
      Portuguese families with peripheral neuropathy caused by a novel mutation in the
      MTMR13/SBF2 gene. CASE REPORT: Family 1: Patient 1: A 30-year-old woman, with
      disease onset in early childhood presented pes cavus and hammertoes and walked
      with a steppage gait. Muscle weakness was present distally, myotactic reflexes
      were abolished and sensory examination revealed a stocking and glove pattern of
      hypoesthesia to all sensory modalities. Family 2: Patient 2: A 43-year-old man,
      second degree cousin of patient 1, born of a consanguineous marriage. At the age
      of 9 months, he was diagnosed with congenital glaucoma on the left eye, with
      progressive visual loss up to total blindness. He presented bilateral claw hand
      deformity, pes cavus and hammertoes and walked with a steppage gait. Myotactic
      reflexes were abolished and muscle weakness was severe distally in the upper and
      lower limbs. Sensory examination revealed a stocking and glove pattern of
      hypoesthesia to all modalities. In both patients electrodiagnostic studies
      evidenced an uniform and generalized sensorimotor demyelinating polyneuropathy
      and the molecular study found a frameshift/truncating homozygous novel mutation
      c.5073_5074del (p.Ser1692Tyrfs*42) in the MTMR13/SBF2 gene. CONCLUSIONS: We
      report a novel mutation in the MTMR13/SBF2 gene associated with a classical CMT
      phenotype. Congenital glaucoma associated with a frameshift/truncating mutation
      in CMT4B2 is reported for the first time.

PMID- 25873784
TI  - Ventricular fibrillation induced by coagulating mode bipolar electrocautery
      during pacemaker implantation in Myotonic Dystrophy type 1 patient.
AB  - The occurrence of ventricular fibrillation, induced by bipolar electrocautery
      during elective dual chamber pacemaker implantation, is reported in a patient
      affected by Myotonic Distrophy type 1 with normal left ventricular ejection
      fraction. 

PMID- 25873785
TI  - Facio-scapulo-humeral muscular dystrophy and its connection with facio
      scapuloperoneal muscular dystrophy 4q35-linked: some historical remarks.

PMID- 25873786
TI  - Effect of positive end-expiratory pressure on porcine right ventricle function
      assessed by speckle tracking echocardiography.
AB  - BACKGROUND: Right ventricle (RV) dysfunction and hypotension can be induced by
      high levels of positive end-expiratory pressure (PEEP). We sought to determine in
      an animal model if a novel ultrasound analysis technique: speckle tracking
      echocardiography (STE), could determine deterioration in RV function induced by
      PEEP and to compare this to a conventional method of RV analysis: fractional area
      change (FAC). STE is a sensitive, angle-independent method for describing cardiac
      deformation ('strain') and is particularly useful in analyzing RV function as has
      been shown in pulmonary hypertension cohorts. METHODS: Ten pigs, 40-90 kg,
      anaesthetized, fully mechanically ventilated at 6 ml/kg were subject to step-wise
      escalating levels of PEEP at two-minute intervals (0, 5, 10, 15, 20, 25 and 30
      cmH20). Intracardiac echocardiography was used to image the RV as transthoracic
      and transesophageal echocardiography did not give sufficient image quality or
      flexibility. Off-line STE analysis was performed using Syngo Velocity Vector
      Imaging (Seimens Medical Solutions Inc., USA). STE systolic parameters are RV
      free wall strain (RVfwS) and strain rate (RVfwSR) and the diastolic parameter RV
      free wall strain rate early relaxation (RVfwSRe). RESULTS: With escalating levels
      of PEEP there was a clear trend of reduction in STE parameters (RVfwS, RVfwSR,
      RVfwSRe) and FAC. Significant hypotension (fall in mean arterial blood pressure
      of 20 mmHg) occurred at approximately PEEP 15 cmH2O. Comparing RVfwS, RVfwSR and
      RVfwSRe values at different PEEP levels showed a significant difference at PEEP 0
      cmH2O vs PEEP 10 cmH2O and above. FAC only showed a significant difference at
      PEEP 0 cmH2O vs PEEP 20 cmH2O and above. 30% of pigs displayed dyssychronous RV
      free wall contraction at the highest PEEP level reached. CONCLUSIONS: STE is a
      sensitive method for determining RV dysfunction induced by PEEP and deteriorated
      ahead of a conventional assessment method: FAC. RVfwS decreased to greater extent
      compared to baseline than FAC, earlier in the PEEP escalation process and showed
      a significant decrease before there was a clinical relevant decrease in mean
      arterial blood pressure. Studies in ICU patients using transthoracic
      echocardiography are warranted to further investigate the most sensitive
      echocardiography method for detecting RV dysfunction induced by mechanical
      ventilation.

PMID- 25873787
TI  - Health research priority setting in selected high income countries: a narrative
      review of methods used and recommendations for future practice.
AB  - Research priority setting aims to gain consensus about areas where research
      effort will have wide benefits to society. While general principles for setting
      health research priorities have been suggested, there has been no critical review
      of the different approaches used. This review aims to: (i) examine methods,
      models and frameworks used to set health research priorities; (ii) identify
      barriers and facilitators to priority setting processes; and (iii) determine the
      outcomes of priority setting processes in relation to their objectives and impact
      on policy and practice. Medline, Cochrane, and PsycINFO databases were searched
      for relevant peer-reviewed studies published from 1990 to March 2012. A review of
      grey literature was also conducted. Priority setting exercises that aimed to
      develop population health and health services research priorities conducted in
      Australia, New Zealand, North America, Europe and the UK were included. Two
      authors extracted data from identified studies. Eleven diverse priority setting
      exercises across a range of health areas were identified. Strategies including
      calls for submission, stakeholder surveys, questionnaires, interviews, workshops,
      focus groups, roundtables, the Nominal Group and Delphi technique were used to
      generate research priorities. Nine priority setting exercises used a core
      steering or advisory group to oversee and supervise the priority setting process.
      None of the models conducted a systematic assessment of the outcomes of the
      priority setting processes, or assessed the impact of the generated priorities on
      policy or practice. A number of barriers and facilitators to undertaking research
      priority setting were identified. The methods used to undertake research priority
      setting should be selected based upon the context of the priority setting process
      and time and resource constraints. Ideally, priority setting should be overseen
      by a multi-disciplinary advisory group, involve a broad representation of
      stakeholders, utilise objective and clearly defined criteria for generating
      priorities, and be evaluated. 

PMID- 25873788
TI  - Comparing the cost effectiveness of harm reduction strategies: a case study of
      the Ukraine.
AB  - BACKGROUND: Harm reduction strategies commonly include needle and syringe
      programmes (NSP), opioid substitution therapy (OST) and interventions combining
      these two strategies. Despite the proven effectiveness of harm-reduction
      strategies in reducing human immunodeficiency virus (HIV) infection among
      injecting drug users (IDUs), no study has compared the cost-effectiveness of
      these interventions, nor the incremental cost effectiveness of combined therapy.
      Using data from the Global Fund, this study compares the cost-effectiveness of
      harm reduction strategies in Eastern Europe and Central Asia, using the Ukraine
      as a case study. METHODS: A Markov Monte Carlo simulation is carried out using
      parameters from the literature and cost data from the Global Fund. Effectiveness
      is presented as both QALYs and infections averted. Costs are measured in 2011 US
      dollars. RESULTS: The Markov Monte Carlo simulation estimates the cost
      effectiveness ratio per infection averted as $487.4 [95% CI: 488.47-486.35] in
      NSP and $1145.9 [95% CI: 1143.39-1148.43] in OST. Combined intervention is more
      costly but more effective than the alternative strategies with a cost
      effectiveness ratio of $851.6[95% CI: 849.82-853.55]. The ICER of the combined
      strategy is $1086.9/QALY [95% CI: 1077.76:1096.24] compared with NSP, and
      $461.0/infection averted [95% CI: 452.98:469.04] compared with OST. These results
      are consistent with previous studies. CONCLUSIONS: Despite the inherent
      limitations of retrospective data, this study provides evidence that harm
      reduction interventions are a cost-effective way to reduce HIV prevalence. More
      research on into cost effectiveness in different settings, and the availability
      of fiscal space for government uptake of programmes, is required.

PMID- 25873789
TI  - Taking the risk: the other side of the story.

PMID- 25873790
TI  - Texas heart institute medal and the Ray C. Fish award for scientific achievement
      in cardiovascular diseases.

PMID- 25873791
TI  - Locked in and locked out.

PMID- 25873792
TI  - Meta-analysis of CHADS2 versus CHA2DS2-VASc for predicting stroke and
      thromboembolism in atrial fibrillation patients independent of anticoagulation.
AB  - Two validated scoring systems for predicting embolic risk, CHADS2 and CHA2DS2
      VASc, contribute to optimizing antithrombotic prescription practices in patients
      who have atrial fibrillation. However, data about anticoagulated patients are
      sparse. We compared CHADS2 and CHA2DS2-VASc, in terms of their predictive risk
      evaluation, in patients with atrial fibrillation who were and were not taking
      anticoagulants. We systematically searched the Cochrane Library, PubMed, and
      Embase databases for studies of the comparative diagnostic performance of CHADS2
      and CHA2DS2-VASc. We identified 12 cohort studies for meta-analysis. With regard
      to the occurrence of cardiovascular events individually, patients with CHA2DS2
      VASc scores >=2 have a greater risk of stroke (risk ratio [RR]=5.15; 95%
      confidence interval [CI], 3.85-6.88; P <0.00001) and thromboembolism (RR=5.96;
      95% CI, 5.50-6.45; P <0.00001) (P diff=0.34) than do patients with CHA2DS2-VASc
      scores <2, independent of anticoagulation therapy (RR=5.76; 95% CI, 5.23-6.35; P
      <0.00001 in anticoagulated patients; and RR=6.12; 95% CI, 5.40-6.93; P <0.00001
      in patients not taking anticoagulants; P diff=0.45). The pooled RR estimates
      indicate an approximate 6-fold increase in the risk of endpoint events in
      patients with CHA2DS2-VASc scores >=2 (RR=5.90; 95% CI, 5.46-6.37; P <0.0001).
      These results clearly indicate the discriminative capacity of the CHA2DS2-VASc
      score for stroke, thromboembolic events, or both, independent of optimal
      anticoagulation. The CHA2DS2-VASc score enables the identification of patients
      who are at genuinely high risk and can direct the selection of appropriate
      therapeutic approaches. 

PMID- 25873793
TI  - Impact and predictors of noncircular left ventricular outflow tract shapes on
      estimating aortic stenosis severity by means of continuity equations.
AB  - Determining aortic stenosis (AS) severity is clinically important. Calculating
      aortic valve (AV) area by means of the continuity equation assumes a circular
      left ventricular outflow tract (LVOT). The full impact of this assumption in
      calculating AV area is unknown. Predictors of noncircular LVOT shape in patients
      with AS are undefined. In 109 adult patients with AS who underwent multiplanar
      transesophageal echocardiography, we calculated AV area by means of the standard
      continuity method and by a modified method involving planimetric LVOT area. We
      found 54 circular, 37 horizontal-oval, 8 vertical-oval, and 10 irregular LVOTs.
      Area derived by direct planimetry correlated better with the modified than the
      standard continuity method (r=0.89 vs r=0.85; both P=0.0001). Valve areas of
      patients with mild, moderate, or severe AS by planimetry were more often
      mischaracterized with use of the standard than modified method (29 vs 18; P
      <0.0001). Horizontal-oval AV area derived by planimetry (1.28 +/- 0.55 cm(2)) was
      underestimated by the standard method (1.05 +/- 0.47 cm(2); P=0.001), but not by
      the modified method. Congenital AV morphology and low cardiac index were the only
      multivariate predictors of horizontal-oval shape. Low cardiac index was the only
      predictor of noncircular shape. More than half our patients with AS had
      noncircular LVOTs. Using the modified method reduces mischaracterizations of AS
      severity. Congenital AV morphology and low cardiac index predict horizontal-oval
      or noncircular shape. These data suggest the value of direct LVOT measurement to
      calculate AS severity in patients who have congenital AV or a low cardiac index. 

PMID- 25873794
TI  - Acute surgical pulmonary embolectomy: a 9-year retrospective analysis.
AB  - Acute pulmonary embolism is a substantial cause of morbidity and death. Although
      the American College of Chest Physicians Evidence-Based Clinical Practice
      Guidelines recommend surgical pulmonary embolectomy in patients with acute
      pulmonary embolism associated with hypotension, there are few reports of 30-day
      mortality rates. We performed a retrospective review of acute pulmonary
      embolectomy procedures performed in 96 consecutive patients who had severe,
      globally hypokinetic right ventricular dysfunction as determined by transthoracic
      echocardiography. Data on patients who were treated from January 2003 through
      December 2011 were derived from health system databases of the New York State
      Cardiac Surgery Reporting System and the Society of Thoracic Surgeons. The data
      represent procedures performed at 3 tertiary care facilities within a large
      health system operating in the New York City metropolitan area. The overall 30
      day mortality rate was 4.2%. Most patients (68 [73.9%]) were discharged home or
      to rehabilitation facilities (23 [25%]). Hemodynamically stable patients with
      severe, globally hypokinetic right ventricular dysfunction had a 30-day mortality
      rate of 1.4%, with a postoperative mean length of stay of 9.1 days. Comparable
      findings for hemodynamically unstable patients were 12.5% and 13.4 days,
      respectively. Acute pulmonary embolectomy can be a viable procedure for patients
      with severe, globally hypokinetic right ventricular dysfunction, with or without
      hemodynamic compromise; however, caution is warranted. Our outcomes might be
      dependent upon institutional capability, experience, surgical ability, and
      careful patient selection. 

PMID- 25873795
TI  - Echocardiographic versus histologic findings in Marfan syndrome.
AB  - This retrospective study attempted to establish the prevalence of multiple-valve
      involvement in Marfan syndrome and to compare echocardiographic with
      histopathologic findings in Marfan patients undergoing valvular or aortic
      surgery. We reviewed echocardiograms of 73 Marfan patients who underwent
      cardiovascular surgery from January 2004 through October 2009. Tissue histology
      was available for comparison in 29 patients. Among the 73 patients, 66 underwent
      aortic valve replacement or the Bentall procedure. Histologic findings were
      available in 29 patients, all of whom had myxomatous degeneration. Of 63 patients
      with moderate or severe aortic regurgitation as determined by echocardiography, 4
      had thickened aortic valves. The echocardiographic findings in 18 patients with
      mitral involvement included mitral prolapse in 15. Of 11 patients with moderate
      or severe mitral regurgitation as determined by echocardiography, 4 underwent
      mitral valve repair and 7 mitral valve replacement. Histologic findings among
      mitral valve replacement patients showed thickened valve tissue and myxomatous
      degeneration. Tricuspid involvement was seen echocardiographically in 8 patients,
      all of whom had tricuspid prolapse. Two patients had severe tricuspid
      regurgitation, and both underwent repair. Both mitral and tricuspid involvement
      were seen echocardiographically in 7 patients. Among the 73 patients undergoing
      cardiac surgery for Marfan syndrome, 66 had moderate or severe aortic
      regurgitation, although their valves manifested few histologic changes. Eighteen
      patients had mitral involvement (moderate or severe mitral regurgitation,
      prolapse, or both), and 8 had tricuspid involvement. Mitral valves were most
      frequently found to have histologic changes, but the tricuspid valve was
      invariably involved. 

PMID- 25873796
TI  - Innovative chimney-graft technique for endovascular repair of a pararenal
      abdominal aortic aneurysm.
AB  - After abdominal aortic aneurysm repair, progressive degeneration of the aneurysm
      can be challenging to treat. Multiple comorbidities and previous operations place
      such patients at high risk for repeat surgery. Endovascular repair is a possible
      alternative; however, challenging anatomy can push the limits of available
      technology. We describe the case of a 71-year-old man who presented with a 5.3-cm
      pararenal aneurysm 4 years after undergoing open abdominal aortic aneurysm
      repair. To avoid reoperation, we excluded the aneurysm by endovascular means,
      using visceral-artery stenting, a chimney-graft technique. Low-profile balloons
      on a monorail system enabled the rapid exchange of coronary wires via a buddy
      wire technique. This novel approach facilitated stenting and simultaneous
      angioplasty of multiple visceral vessels and the abdominal aorta. 

PMID- 25873797
TI  - Improved systemic saturation after ventricular assist device implantation in a
      patient with decompensated dextro-transposition of the great arteries after the
      Fontan procedure.
AB  - We report the successful implantation of a HeartMate II left ventricular assist
      device after a failed Fontan procedure in a patient with dextro-transposition of
      the great arteries. The patient had developed significant intrapulmonary
      arteriovenous shunting. Despite the theoretical risk of worsening intrapulmonary
      shunting due to the decrease in systemic vascular resistance after device
      implantation, our patient did well. He was discharged from the hospital in stable
      condition and had better oxygen saturation than before the device was implanted.
      To our knowledge, ours is the 2nd report of the use of a ventricular assist
      device after the failure of a Fontan procedure, and the first report concerning
      the effect of ventricular assist device implantation on intrapulmonary shunting. 

PMID- 25873798
TI  - Actinomycotic endocarditis of the eustachian valve: a rare case and a review of
      the literature.
AB  - Eustachian valve endocarditis caused by Actinomyces species is extremely rare. A
      literature review revealed only one reported case-caused by Actinomyces israelii
      in an intravenous drug abuser. Our patient, a 30-year-old woman who at first
      appeared to be in good health, presented with fever, a large mobile mass on the
      eustachian valve, and extensive intra-abdominal and pelvic masses that looked
      malignant. Histopathologic examination of tissue found in association with an
      intrauterine contraceptive device revealed filamentous, branching microorganisms
      consistent with Actinomyces turicensis. This patient was treated successfully
      with antibiotic agents. In addition to presenting a new case of a rare condition,
      we discuss cardiac actinomycotic infections in general and eustachian valve
      endocarditis in particular: its predisposing factors, clinical course, sequelae,
      and our approaches to its management. 

PMID- 25873799
TI  - Exercise-induced pulmonary artery hypertension in a patient with compensated
      cardiac disease: hemodynamic and functional response to sildenafil therapy.
AB  - We describe the case of a 54-year-old man who presented with exertional dyspnea
      and fatigue that had worsened over the preceding 2 years, despite a normally
      functioning bioprosthetic aortic valve and stable, mild left ventricular
      dysfunction (left ventricular ejection fraction, 0.45). His symptoms could not be
      explained by physical examination, an extensive biochemical profile, or multiple
      cardiac and pulmonary investigations. However, abnormal cardiopulmonary exercise
      test results and a right heart catheterization-combined with the use of a symptom
      limited, bedside bicycle ergometer-revealed that the patient's exercise-induced
      pulmonary artery hypertension was out of proportion to his compensated left heart
      disease. A trial of sildenafil therapy resulted in objective improvements in
      hemodynamic values and functional class. 

PMID- 25873800
TI  - Bacterial pancarditis with myocardial abscess: successful surgical intervention
      in a 14-month-old boy.
AB  - A 14-month-old boy with a structurally normal heart presented with signs of
      cardiac tamponade caused by purulent pericarditis. During his hospital stay,
      mitral and tricuspid valve endocarditis developed, and a ventricular septal
      abscess expanded despite appropriate, prolonged antibiotic therapy for
      methicillin-resistant Staphylococcus aureus. The day before scheduled surgical
      correction, the abscess ruptured, creating a septal aneurysm. Surgical
      intervention resulted in an excellent outcome. Throughout the patient's 67-day
      hospitalization, the use of echocardiography was crucial in monitoring and
      diagnosis. In addition to reporting this case, we discuss our diagnostic and
      treatment considerations. To our knowledge, this is only the 4th report of S.
      aureus bacterial pancarditis with myocardial abscess. 

PMID- 25873801
TI  - Incidental left atrial blood cyst in a patient undergoing transcatheter aortic
      valve replacement.
AB  - Blood cysts of the heart are benign cardiovascular tumors found incidentally in
      approximately 50% of infants who undergo autopsy at less than 2 months of age.
      These congenital cysts, frequently present on the atrioventricular valves of
      infants, are exceedingly rare in adults. Nonetheless, in adults, cardiac blood
      cysts have been found on the mitral valve, papillary muscles, right atrium, right
      ventricle, left ventricle, and aortic, pulmonic, and tricuspid valves. Reported
      complications include left ventricular outflow obstruction, occlusion of the
      coronary arteries, valvular stenosis or regurgitation, and embolic stroke. In
      high-risk patients with severe aortic stenosis, transcatheter aortic valve
      replacement has emerged as an alternative to surgical replacement.
      Transesophageal echocardiography plays a fundamental role in evaluating the
      feasibility of intraprocedural transcatheter aortic valve replacement, in
      measuring aortic annular size, in guiding placement of the prosthetic device, and
      in looking for possible complications. The embolic risk of rapid pacing and
      transcatheter aortic valve replacement in a patient with an intracardiac blood
      cyst is unknown, and such a case has not, to our knowledge, been reported
      heretofore. We present the case of a 78-year-old woman with severe aortic
      stenosis, in whom a blood cyst was incidentally found in the left atrium upon
      transesophageal echocardiography. She underwent successful transcatheter aortic
      valve replacement without embolic complication. 

PMID- 25873802
TI  - Iliac artery aneurysm repair with preservation of a single ectopic pelvic kidney.
AB  - An ultrasonographic study in a 60-year-old man incidentally detected an iliac
      artery aneurysm that gave rise to the renal artery of a single ectopic pelvic
      kidney. Renal-preservation solution could not be used during surgery, because the
      unclamped renal vein would have enabled the solution to enter the systemic
      circulation. Therefore, cold saline solution was infused through the renal
      ostium, and the kidney was maintained under cold saline immersion. We performed
      aortoiliac bypass and then implanted the renal artery into the bypass graft.
      Postoperatively, the patient's serum creatinine level increased; after one year,
      his renal function was normal. We discuss our use of cold saline solution for
      renal preservation. 

PMID- 25873803
TI  - Cardiomyopathy induced by pulmonary sequestration in a 50-year-old man.
AB  - A 50-year-old black man presented at the emergency department with midsternal,
      nonradiating chest pressure and chronic dyspnea on exertion. Four years before
      the current admission, he had been diagnosed with nonischemic cardiomyopathy at
      another facility. After our complete evaluation, we suspected that his symptoms
      arose from left-to-left shunting in association with pulmonary sequestration, a
      congenital malformation. Our preliminary diagnosis of secondary dilated
      cardiomyopathy was confirmed by normalization of the patient's ventricular size
      and function after lobectomy. To our knowledge, this patient is the oldest on
      record to present with cardiomyopathy consequent to pulmonary sequestration. His
      case is highly unusual because of his age and the rapid resolution of his
      symptoms after lobectomy. We believe that pulmonary sequestration should be
      included in the differential diagnosis of dilated cardiomyopathy. 

PMID- 25873804
TI  - Early detection of a cavopulmonary tumor embolus with the use of transesophageal
      echocardiography.
AB  - Pulmonary tumor embolization from renal cell carcinoma is associated with severe
      cardiopulmonary morbidity and high perioperative mortality rates. We report the
      case of a 71-year-old woman who presented with right-sided abdominal pain.
      Magnetic resonance images revealed a mass originating from the upper pole of the
      right kidney and extending into the infrahepatic portion of the inferior vena
      cava. Transesophageal echocardiography was continuously used to monitor the mass
      during intended radical nephrectomy and tumor resection. When the right kidney
      was mobilized, intracaval thrombus detached and migrated to the patient's right
      atrium, causing severe hemodynamic instability. After emergent sternotomy and
      during the initiation of cardiopulmonary bypass, the mass was no longer
      echocardiographically detectable in the heart; it was soon removed completely
      from the left pulmonary artery. The mass was a renal cell carcinoma. We recommend
      the use of transesophageal echocardiography as an efficient diagnostic tool in
      the early detection of pulmonary tumor embolization during the resection of renal
      cell carcinoma that involves the inferior vena cava. 

PMID- 25873805
TI  - Lambl's excrescence, migrainous headaches, and "tiger stripes": puzzling findings
      in one patient.
AB  - Lambl's excrescences are mobile, thin, filiform structures that occur at sites of
      valve closure. Even though many clinicians consider them to be part of the normal
      aging process, evidence suggests an association between Lambl's excrescences and
      ischemic stroke, migrainous headaches, and acute coronary syndromes. As a thin
      filamentous structure, a Lambl's excrescence is better detected and characterized
      with transesophageal than with transthoracic echocardiography. Intracardiac
      oscillatory structures can also be seen as "tiger stripes" on spectral pulsed
      Doppler echocardiographic recordings. Herein, we present the case of a 68-year
      old woman who had 3 concurrent enigmatic findings with unclear correlation:
      migrainous headaches, Lambl's excrescences, and the uncommon finding of "tiger
      stripes" on spectral Doppler echocardiography. We discuss the possible
      correlation between these 3 findings and review the available literature on
      Lambl's excrescences and tiger stripes. 

PMID- 25873807
TI  - Hemodynamic evaluation of suspected severe aortic stenosis leads to a diagnosis
      of renal cell carcinoma.
AB  - The evaluation of aortic stenosis is not always straightforward. When symptoms of
      severe aortic stenosis are present with supporting Doppler echocardiographic or
      cardiac catheterization data, replacement of the aortic valve is recommended.
      Occasionally, Doppler- and catheter-derived data are discordant; appropriate
      treatment in such cases becomes less clear. We report a case in which a 66-year
      old man's symptoms and Doppler data suggested severe aortic stenosis. However,
      heart catheterization data suggested otherwise, and ultimately it led to the
      diagnosis of a highly vascular renal tumor. Shunting within the tumor resulted in
      high cardiac output, which, in combination with a small aortic root, masqueraded
      as severe aortic stenosis. 

PMID- 25873806
TI  - Left ventricular noncompaction in a family with lamin A/C gene mutation.
AB  - Left ventricular noncompaction is a rare type of cardiomyopathy, the genetics of
      which are poorly understood to date. Lamin A/C gene mutations have been
      associated with dilated cardiomyopathy and diseases of the conduction system, but
      rarely in left ventricular noncompaction cardiomyopathy. This report describes
      the cases of 4 family members with a lamin A/C gene mutation, 3 of whom had
      phenotypic expression of left ventricular noncompaction. 

PMID- 25873808
TI  - Restoration of renal allograft function via reduced-contrast percutaneous
      revascularization of transplant renal artery stenosis.
AB  - Transplant renal artery stenosis (TRAS), the most common vascular complication of
      kidney transplantation, can lead to heart failure, uncontrolled hypertension, and
      irreversible dysfunction of the transplanted kidney. Percutaneous
      revascularization can improve outcomes in well-selected patients with symptomatic
      TRAS, but the intervention itself poses risk to the transplanted kidney because
      of the quantities of nephrotoxic contrast solution that often are used. We report
      the case of a patient with TRAS who, 5 months after undergoing a kidney
      transplant, developed allograft dysfunction and heart failure that required
      hemodialysis. We performed angioplasty and stenting of the TRAS, using
      intravascular ultrasonography and fluoroscopy as our primary imaging methods. To
      minimize further damage to a potentially viable kidney, the volume of
      intravascular contrast medium used was trivial (a total of 9 cc).
      Revascularization of the patient's TRAS restored his renal function: within 4
      weeks of the procedure, he no longer needed hemodialysis, and his heart failure
      symptoms had resolved. This case emphasizes the value of early definitive
      treatment of TRAS and the usefulness of intravascular ultrasonography to minimize
      the amount of contrast medium used in endovascular procedures. 

PMID- 25873809
TI  - Ochronotic involvement of the aortic and mitral valves in a 72-year-old man.
AB  - Ochronosis, an autosomal recessive metabolic disorder, causes an excess of
      homogentisic acid that results in adverse pigmentation, calcification, and
      inflammation of cartilaginous and other tissues. Cardiovascular abnormalities are
      less frequently reported than are other manifestations. In rare cases, ochronosis
      can cause valvular heart disease. We report the case of a 72-year-old man with
      aortic stenosis and mitral insufficiency who was diagnosed with ochronosis while
      undergoing surgical aortic and mitral valve replacement. We discuss the history
      and surgical management of alkaptonuric ochronosis. 

PMID- 25873810
TI  - Right ventricular free wall strain: a predictor of successful left ventricular
      assist device implantation.

PMID- 25873811
TI  - Abdominal aortic aneurysm and sarcoidosis: rare presentation of an uncommon
      disease.

PMID- 25873812
TI  - Persistent 5th aortic arch with coexisting discontinuous pulmonary arteries,
      double-outlet right ventricle, and complete atrioventricular septal defect.

PMID- 25873813
TI  - Methylprednisolone-induced transient ventricular dysfunction.

PMID- 25873814
TI  - Single coronary artery.

PMID- 25873816
TI  - Erratum.

PMID- 25873815
TI  - Giant coronary artery aneurysms.

PMID- 25873817
TI  - When the chief complaint tells it all.

PMID- 25873818
TI  - Overcoming indignities with dignity.

PMID- 25873819
TI  - Pathways involved in interleukin-1beta-mediated murine cardiomyocyte apoptosis.
AB  - Accumulating evidence suggests that interleukin-1 (IL-1) signaling plays an
      essential role in the pathogenesis of heart failure by inducing cardiomyocyte
      apoptosis, but the mechanisms of this process are poorly defined. We further
      explored these molecular pathways. We isolated cardiomyocytes from neonatal mice
      and then cultured and stimulated them with murine IL-1beta in vitro. Cell
      apoptotic ratios were measured by means of flow cytometry. Expression of effector
      molecules was analyzed by means of enzyme-linked immunosorbent assay, Western
      blotting, and real-time quantitative polymerase chain reaction. The results
      showed that IL-1beta induced murine cardiomyocyte apoptosis through a release of
      cytochrome c into cytoplasm and through caspase 3 activation. Simultaneously, IL
      1beta signaling promoted expression of endonuclease G and high-temperature
      requirement protein A2 messenger RNA. Survivin and X-linked inhibitors of
      apoptosis protein (IAP), members of the IAP family, were inhibited on the
      messenger RNA level during IL-1beta-mediated cardiomyocyte apoptosis. We found
      that IL-1beta signaling during cardiomyocyte apoptosis in vitro induced the
      activation of caspase-dependent and caspase-independent pathways, and inhibited
      IAPs. Understanding the molecular mechanisms involved in IL-1beta-mediated
      cardiomyocyte apoptosis might assist in the design of therapeutic approaches to
      protect cardiomyocyte function and prevent heart failure. 

PMID- 25873820
TI  - Regression of left ventricular mass after implantation of the sutureless 3f
      Enable aortic bioprosthesis.
AB  - Left ventricular hypertrophy in aortic stenosis is considered a compensatory
      response for the maintenance of systolic function but a risk factor for cardiac
      morbidity and death. We investigated the degree of left ventricular mass
      regression after implantation of the sutureless Medtronic 3f Enable Aortic
      Bioprosthesis. We studied 19 patients who, from May 2010 through July 2011,
      underwent isolated aortic valve replacement with the 3f Enable bioprosthetic
      valve, with clinical and echocardiographic follow-up at 6 months. The mean age
      was 77.1 +/- 5.1 years (range, 68-86 yr); 14 patients were women (73.7%); and the
      mean logistic EuroSCORE was 15.4% +/- 11.8%. Echocardiography was performed
      preoperatively, at discharge, and at 6 months' follow-up. The left ventricular
      mass was calculated by means of the Devereux formula and indexed to body surface
      area. The left ventricular mass index decreased from 146.1 +/- 47.6 g/m(2) at
      baseline to 118.1 +/- 39.8 g/m(2) at follow-up (P=0.003). The left ventricular
      ejection fraction did not change significantly. The mean transaortic gradient
      decreased from 57.3 +/- 14.2 mmHg at baseline to 12.3 +/- 4.6 mmHg at discharge
      and 12.2 +/- 5.3 mmHg at follow-up (P <0.001), and these decreases were
      accompanied by substantial clinical improvement. No moderate or severe
      paravalvular leakage was present at discharge or at follow-up. In isolated aortic
      stenosis, aortic valve replacement with the 3f Enable bioprosthesis results in
      significant regression of left ventricular mass at 6 months' follow-up. However,
      this regression needs to be verified by long-term echocardiographic follow-up.

PMID- 25873821
TI  - Anthracycline treatment and ventricular remodeling in left ventricular assist
      device patients.
AB  - Nonischemic cardiomyopathy can complicate antineoplastic therapy and lead to
      irreversible heart failure. We evaluated structural changes at the time of left
      ventricular assist device implantation in heart failure patients who had been
      exposed to anthracycline, and we correlated those changes with clinical
      presentation. We retrospectively studied left ventricular core samples taken at
      implantation of the HeartMate II left ventricular assist device in 12 heart
      failure patients (mean age, 46 +/- 16 yr) who had histories of anthracycline
      exposure. We evaluated those samples for hypertrophy, myocytolysis, and fibrosis.
      Histopathologic findings showed moderate-to-severe myocyte hypertrophy, moderate
      myocytolysis, and perivascular and interstitial fibrosis with areas of
      replacement fibrosis. Ultrastructural studies revealed marked decreases in
      myofibrils, diffuse mitochondrial swelling, and disorganization of the
      sarcoplasmic reticulum. The interval between anthracycline therapy and heart
      failure was a mean of 6.8 +/- 5.7 years; duration of heart failure symptoms, 38
      +/- 47 months; and duration of device support, 414 +/- 266 days. Four patients
      are continuing on device support, 3 have undergone transplantation, 3 have
      undergone device explantation, and 2 have died. The time of heart failure onset
      and the duration of symptoms did not correlate with the severity and extent of
      the histopathologic changes. The histopathologic findings and the clinical course
      varied in heart failure patients with anthracycline exposure. No correlation was
      observed between anthracycline therapy and the development or duration of heart
      failure symptoms, severity of histopathologic changes, or outcomes. 

PMID- 25873822
TI  - Papillary fibroelastoma of the aortic valve: analysis of 21 cases, including a
      presentation with cardiac arrest.
AB  - Cardiac papillary fibroelastoma is a rare, benign tumor, arising predominantly
      from cardiac valves. This tumor can cause a variety of symptoms due to
      thromboembolism. We describe our single-center surgical experience with papillary
      fibroelastoma of the aortic valve. From April 2004 through June 2013, 6,530
      patients underwent cardiac surgery. Of those, 6,098 patients were included in the
      final analysis. Twenty-one patients (0.34%) underwent surgical resection of 30
      papillary fibroelastomas of the aortic valve. Most patients (67%) were
      incidentally diagnosed to have cardiac papillary fibroelastoma. The usual symptom
      was cerebral infarction (in 5 of 7 symptomatic patients). A rare presentation of
      papillary fibroelastoma in one patient was cardiac arrest caused by left main
      coronary artery ostial obstruction. Tumor size was not related to patient age
      (Pearson correlation coefficient, 0.34; P=0.13). Neither the number of tumors
      (1.43 +/- 0.72 vs 1.43 +/- 0.62) nor tumor size (8.14 +/- 2.42 vs 8.07 +/- 3.31
      mm) was significantly different between symptomatic and asymptomatic patients.
      All lesions were resected by means of the simple shave technique. There were no
      operative or 30-day deaths. Follow-up echocardiograms showed no tumor recurrence
      (mean follow-up duration, 17 +/- 14 mo). We identified no significant
      relationship among tumor size, number of tumors, symptoms, or patient age.
      Because simple shave excision of the tumor can be safely achieved without
      evidence of tumor recurrence, we conclude that surgical resection can be
      reasonable in asymptomatic patients. 

PMID- 25873823
TI  - Prolonged chest compressions during cardiopulmonary resuscitation for in-hospital
      cardiac arrest due to acute pulmonary embolism.
AB  - Patients with hemodynamic collapse due to acute pulmonary embolism have a dismal
      prognosis if not treated rapidly. Therapeutic options include systemic
      thrombolytic therapy, rheolytic thrombectomy, and surgical embolectomy. However,
      the efficacy of thrombolytic therapy is diminished because the low-output state
      hinders effective delivery of the lytic agent to the thrombus. In the absence of
      any form of mechanical circulatory support, such as extracorporeal membrane
      oxygenation or cardiac surgery on site, we think that prolonged vigorous manual
      compressions might be the only way to support the circulation during the initial
      critical state, when thrombolytic therapy has been administered. We report the
      results of prolonged manual chest compressions (exceeding 30 minutes) on 6
      patients who received tenecteplase in treatment of acute pulmonary embolism that
      induced in-hospital cardiopulmonary arrest. Four of 6 patients survived and were
      discharged from the hospital. In an era of increasing technologic complexity for
      patients with hemodynamic instability, we emphasize the importance of prolonged
      chest compressions, which can improve systemic perfusion, counteract the
      prothrombotic state associated with cardiopulmonary arrest, and give the lytic
      agent time to act. 

PMID- 25873824
TI  - Subcutaneous implantable cardioverter-defibrillators: expanding the scope of
      technology.

PMID- 25873825
TI  - Subcutaneous implantable cardioverter-defibrillator implantation in a patient
      with a left ventricular assist device already in place.
AB  - A 56-year-old man with ischemic cardiomyopathy, a biventricular implantable
      cardioverter-defibrillator (ICD), and a left ventricular assist device (LVAD)
      developed a pocket hematoma and infection after an ICD generator change. The
      biventricular ICD was extracted, and the patient was given a full course of
      antibiotics. Because he had no indications for bradycardia pacing or
      biventricular pacing, he was implanted with a subcutaneous ICD under full
      anticoagulation. There was no interference in sensing or shock delivery from the
      ICD. The LVAD readings were unchanged during and after the procedure. The patient
      had an uneventful postoperative course, and both devices were functioning
      normally. To our knowledge, this is the first reported case of the implantation
      of a subcutaneous ICD in the presence of an LVAD. This report illustrates that
      both devices can be implanted successfully in the same patient. In addition, the
      subcutaneous ICD minimizes the risk of bloodstream infections, which can be fatal
      in patients who have life-supporting devices such as an LVAD. 

PMID- 25873826
TI  - Transcatheter aortic valve implantation despite challenging vascular access.
AB  - We describe transcatheter aortic valve implantation in a patient who had severe
      peripheral artery disease. The patient's vascular condition required additional
      preliminary peripheral intervention to enable adequate vascular access. A 78-year
      old man with severe aortic stenosis, substantial comorbidities, and severe heart
      failure symptoms was referred for aortic valve replacement. The patient's 20-mm
      aortic annulus necessitated the use of a 23-mm Edwards Sapien valve inserted
      through a 22F sheath, which itself needed a vessel diameter of at least 7 mm for
      percutaneous delivery. The left common femoral artery was selected for valve
      delivery. The left iliac artery and infrarenal aorta underwent extensive
      intervention to achieve an intraluminal diameter larger than 7 mm. After aortic
      valvuloplasty, valve deployment was successful, and the transaortic gradient
      decreased from 40 mmHg to less than 5 mmHg. The patient was discharged from the
      hospital 4 days postoperatively. We conclude that transcatheter aortic valve
      implantation can be successfully performed in patients with obstructed vascular
      access, including stenosis of the infrarenal aorta and the subclavian and
      coronary arteries. 

PMID- 25873827
TI  - Conservative management of chylothorax after coronary artery bypass grafting.
AB  - Chylothorax is a rare sequela to cardiac surgery, associated with high rates of
      morbidity and mortality. There are various medical and surgical options for its
      management. We describe 2 cases of chylothorax that developed after coronary
      artery bypass grafting and were managed successfully with medical therapy alone.
      Conservative treatment such as we describe aims to reduce chyle flow, to drain
      the pleural cavity in an effective manner, and to prevent chronic sequelae.
      Optimal conservative treatment, consisting of nothing by mouth and the
      administration of a pleurodetic agent, should be started immediately upon
      diagnosis. In most cases, it reduces the need for reoperation and long-term
      hospitalization. Prospective randomized controlled trials are nonetheless needed
      to confirm these assumptions. 

PMID- 25873828
TI  - Minimal use of fluoroscopy to reduce fetal radiation exposure during
      radiofrequency catheter ablation of maternal supraventricular tachycardia.
AB  - Electrophysiologic procedures in the young engender concern about the potential
      long-term effects of radiation exposure. This concern is manifold if such
      procedures are contemplated during pregnancy. Catheter ablations in pregnancy are
      indicated only in the presence of an unstable tachycardia that cannot be
      controlled by antiarrhythmic agents. This report describes the case of an 18-year
      old pregnant woman and our stratagem to minimize irradiation of the mother and
      the fetus. 

PMID- 25873829
TI  - Clozapine-induced myocarditis: recognizing a potentially fatal adverse reaction.
AB  - A 46-year-old man with a history of paranoid schizophrenia was admitted with a
      recurrence of psychotic symptoms. Improvement was noted after the initiation of
      clozapine. After 2 weeks of clozapine therapy, chest pressure and abnormal
      cardiac biomarkers (in the presence of a normal coronary angiogram) raised
      suspicion of myocarditis. That diagnosis was confirmed by means of cardiac
      magnetic resonance imaging. Discontinuation of the clozapine led to resolution of
      the cardiac symptoms. Clozapine-induced myocarditis is rare and can be missed for
      lack of specific clinical findings. In order to prevent disease progression and a
      possibly fatal outcome, early recognition of the condition and prompt
      discontinuation of clozapine are necessary. 

PMID- 25873830
TI  - Primary percutaneous coronary intervention for ST-segment-elevation myocardial
      infarction in a patient taking dabigatran for chronic anticoagulation.
AB  - Interventional cardiologists have few data on which to base clinical decisions
      regarding optimal care for ST-segment-elevation myocardial infarction patients
      who are taking therapeutic chronic oral anticoagulation. We present what we
      believe to be the first reported case of emergency coronary angiography and
      primary percutaneous coronary intervention in an ST-segment-elevation myocardial
      infarction patient who was on a dabigatran regimen for atrial fibrillation. The
      patient tolerated the procedures well and had no observable bleeding sequelae. In
      addition to the patient's case, we discuss the current evidence regarding the
      periprocedural management of oral anticoagulation in patients who need coronary
      angiography and percutaneous coronary intervention. 

PMID- 25873831
TI  - Free internal mammary artery graft reimplantation on the same vessel in repeat
      coronary revascularization.
AB  - We describe the case of a 62-year-old man who needed a 3-vessel coronary artery
      bypass reoperation and mitral valve replacement. The patient's existing free left
      internal mammary artery graft was not functioning because of a critical stenosis
      in the native vessel just after the distal anastomosis. The free graft itself was
      in perfect condition, and we decided to reuse it. Because the course of the graft
      was so tortuous, we concluded that skeletonization would yield the extra length
      needed for reimplantation. After reimplanting the graft, we performed venous
      grafting and mitral valve replacement. The patient was well and had no signs of
      ischemia at 29 months postoperatively. There have been few reports on recycling
      internal mammary artery grafts in repeat coronary artery bypass grafting. To our
      knowledge, ours is the first report of the reimplantation of a free internal
      mammary artery graft on the same vessel. We describe the procedure and our
      decision-making process. 

PMID- 25873832
TI  - Complete atrioventricular septal defect and pulmonary stenosis diagnosed in a 49
      year-old woman after 10 uneventful births.
AB  - Atrioventricular septal defects constitute 4% of all congenital cardiac
      malformations. Patients with complete atrioventricular septal defect rarely
      survive for decades without surgical treatment. Pulmonary stenosis can provide a
      delicate balance between the pulmonary and systemic circulations and thereby
      increase longevity. We present the case of a 49-year-old woman whose complete
      atrioventricular septal defect and associated pulmonary stenosis were diagnosed
      only after she had given birth to 10 live children through uneventful spontaneous
      delivery. We discuss her successful surgical treatment in terms of the available
      medical literature. 

PMID- 25873833
TI  - Prenatal diagnosis of left pulmonary artery-to-pulmonary vein fistula and its
      successful surgical repair in a neonate.
AB  - Pulmonary arteriovenous fistula is a rare disease. To the best of our knowledge,
      prenatal diagnosis of a fistula between the left pulmonary artery and the left
      pulmonary vein has not been described in the medical literature. We report a case
      of the prenatal diagnosis of a left pulmonary artery-to-pulmonary vein fistula,
      followed by successful neonatal surgical repair. 

PMID- 25873834
TI  - Prosthetic valve endocarditis with valvular obstruction after transcatheter
      aortic valve replacement.
AB  - Patients with severe aortic stenosis who are at high risk for open-heart surgery
      might be candidates for transcatheter aortic valve replacement (TAVR). To our
      knowledge, this is the first report of Streptococcus viridans endocarditis that
      caused prosthetic valve obstruction after TAVR. A 77-year-old man who had
      undergone TAVR 17 months earlier was admitted because of evidence of prosthetic
      valve endocarditis. A transthoracic echocardiogram revealed a substantial
      increase in the transvalvular peak gradient and mean gradient in comparison with
      an echocardiogram of 7 months earlier. A transesophageal echocardiogram showed a
      1.5-cm vegetation obstructing the valve. Blood cultures yielded penicillin
      sensitive S. viridans. The patient was hemodynamically stable and was initially
      treated with vancomycin because of his previous penicillin allergy. Subsequent
      therapy with levofloxacin, oral penicillin (after a negative penicillin skin
      test), and intravenous penicillin eliminated the symptoms of the infection.
      Transcatheter aortic valve replacement is a relatively new procedure, and
      sequelae are still being discovered. We recommend that physicians consider
      obstructive endocarditis as one of these. 

PMID- 25873835
TI  - Dazed, confused, and asystolic: possible signs of anti-N-methyl-D-aspartate
      receptor encephalitis.
AB  - Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is a rare panencephalitis
      that can present with severe cardiac dysrhythmias. We present a case of a 19-year
      old woman with no significant medical history who presented with progressive
      changes in mental status and profound ictal asystole that necessitated the
      placement of an external temporary pacemaker. She was diagnosed with and treated
      for anti-NMDA receptor encephalitis, and she recovered after a prolonged and
      complicated hospitalization. We review the pathophysiology and management of anti
      NMDA receptor encephalitis, as well as its cardiac manifestations. 

PMID- 25873836
TI  - Left atrial wall dissection: a rare sequela of native-valve endocarditis.
AB  - Left atrial wall dissection is a rare condition; most cases are iatrogenic after
      mitral valve surgery. A few have been reported as sequelae of blunt chest trauma,
      acute myocardial infarction, and invasive cardiac procedures. On occasion,
      infective endocarditis causes left atrial wall dissection. We report a highly
      unusual case in which a 41-year-old man presented with native mitral valve
      infective endocarditis that had caused left atrial free-wall dissection. Although
      our patient died within an hour of presentation, we obtained what we consider to
      be a definitive diagnosis of a rare sequela, documented by transthoracic and
      transesophageal echocardiography. 

PMID- 25873837
TI  - Fractured inferior vena cava filter strut presenting with ST-segment elevation
      and cardiac tamponade.
AB  - The fracture of an inferior vena cava filter strut and its migration to the heart
      is a rare sequela of implanted inferior vena cava filters. Perforation through
      the right ventricle into the pericardium with resultant cardiopulmonary
      compromise is even less frequent. We report the case of a 53-year-old man who
      presented with chest pain and hypotension consequent to cardiac tamponade. A
      fractured inferior vena cava filter strut had migrated and perforated his right
      ventricle. The fractured strut was successfully removed by means of cardiac
      surgery. Inferior vena cava filters should be placed when necessary to minimize
      the risk of pulmonary embolism, and regular radiologic monitoring should be
      performed; however, the eventual extraction of retrievable filters should be
      considered. In addition to discussing the patient's case, we briefly review the
      relevant medical literature. 

PMID- 25873838
TI  - Regression of a large congenital hepatic arteriovenous malformation.
AB  - Congenital hepatic arteriovenous malformations are rarely seen in association
      with persistent neonatal pulmonary hypertension. We report the case of a full
      term female newborn who presented with heart failure and respiratory distress
      soon after birth. Echocardiographic investigation revealed severe persistent
      pulmonary hypertension and patent ductus arteriosus. Here we report spontaneous
      regression in size of both the feeder vessel and the vascular bed of the
      congenital hepatic arteriovenous malformation. We postulate that our conservative
      use of oral heart failure therapy, in the form of diuretic agents and captopril,
      decreased the congestion and diameter of the affected vessels. 

PMID- 25873839
TI  - Vertebral erosion due to spontaneous thoracic aortic false aneurysm.

PMID- 25873840
TI  - Takotsubo Syndrome as a Comorbidity, and the Need for a Change in our Mindset.

PMID- 25873841
TI  - Acceptability and practicality of a Spanish translation of paediatric Gait Arms
      Legs and Spine (pGALS) in Peruvian children.
AB  - BACKGROUND: The paediatric Gait, Arms, Legs and Spine (pGALS) musculoskeletal
      examination tool is validated for use in school-aged English Speaking children
      and shown to be practical and effective in acute paediatric practice in the UK
      and Malawi. Our aim was to assess the acceptability and practicality of a Spanish
      translation of pGALS in an acute paediatric setting in Peru. FINDINGS: Fifty
      three school-aged children presenting to Hospital Regional de Loreto, Peru were
      recruited to undergo a pGALS examination using a Spanish translation of the
      instructions. The pGALS examination was completed in 92.5% (49/53), with the time
      taken (median 4.42 minutes) being acceptable to most parents (98.1%, 52/53). Most
      children (88.7%, 47/53), found the pGALS examination caused 'little' or 'no
      additional discomfort'. Using pGALS, significant findings were observed in 18/53
      (34%) children; these related to fractures (4/18), hypermobility (4/18),
      infectious causes (5/18) and soft tissue trauma (5/18). CONCLUSION: Using this
      Spanish translation, pGALS assessment was practical, acceptable and effective in
      detecting musculoskeletal changes in many children.

PMID- 25873842
TI  - Physical and chemical mechanisms in oxide-based resistance random access memory.
AB  - In this review, we provide an overview of our work in resistive switching
      mechanisms on oxide-based resistance random access memory (RRAM) devices. Based
      on the investigation of physical and chemical mechanisms, we focus on its
      materials, device structures, and treatment methods so as to provide an in-depth
      perspective of state-of-the-art oxide-based RRAM. The critical voltage and
      constant reaction energy properties were found, which can be used to
      prospectively modulate voltage and operation time to control RRAM device working
      performance and forecast material composition. The quantized switching phenomena
      in RRAM devices were demonstrated at ultra-cryogenic temperature (4K), which is
      attributed to the atomic-level reaction in metallic filament. In the aspect of
      chemical mechanisms, we use the Coulomb Faraday theorem to investigate the
      chemical reaction equations of RRAM for the first time. We can clearly observe
      that the first-order reaction series is the basis for chemical reaction during
      reset process in the study. Furthermore, the activation energy of chemical
      reactions can be extracted by changing temperature during the reset process, from
      which the oxygen ion reaction process can be found in the RRAM device. As for its
      materials, silicon oxide is compatible to semiconductor fabrication lines. It is
      especially promising for the silicon oxide-doped metal technology to be
      introduced into the industry. Based on that, double-ended graphene oxide-doped
      silicon oxide based via-structure RRAM with filament self-aligning formation, and
      self-current limiting operation ability is demonstrated. The outstanding device
      characteristics are attributed to the oxidation and reduction of graphene oxide
      flakes formed during the sputter process. Besides, we have also adopted a new
      concept of supercritical CO2 fluid treatment to efficiently reduce the operation
      current of RRAM devices for portable electronic applications. 

PMID- 25873843
TI  - Application of silicalite-modified electrode for the development of sucrose
      biosensor with improved characteristics.
AB  - The application of silicalite for improvement of working characteristics of
      conductometric enzyme biosensors for determination of sucrose was studied in this
      research. Biosensors based on different types of silicalite-modified electrodes
      were studied and compared according to their analytical characteristics.
      Polyethylenimine/glutaraldehyde/silicalite-modified biosensors showed higher
      sensitivity compared with others type of biosensors. Moreover, the
      polyethylenimine/glutaraldehyde/silicalite sucrose biosensors were characterized
      by high selectivity and signal reproducibility (relative standard deviation (RSD)
      = 2.78% for glucose measurements and RSD = 3.2% for sucrose measurements).
      Proposed biosensors were used for determination of sucrose in different samples
      of beverages. The obtained results had good correlation with results obtained by
      HPLC. Thus, polyethylenimine/glutaraldehyde/silicalite-modified biosensors have
      shown perspective characteristics for the development of effective conductometric
      enzyme biosensors. 

PMID- 25873845
TI  - Editor's Introduction to This Issue.

PMID- 25873844
TI  - Integrating mental and physical health care: lessons from the Second World
      Congress on Integrated Care in Sydney.

PMID- 25873846
TI  - Genes Involved in the Biosynthesis and Transport of Acinetobactin in
      Acinetobacter baumannii.
AB  - Pathogenic bacteria survive in iron-limited host environments by using several
      iron acquisition mechanisms. Acinetobacter baumannii, causing serious infections
      in compromised patients, produces an iron-chelating molecule, called
      acinetobactin, which is composed of equimolar quantities of 2,3-dihydroxybenzoic
      acid (DHBA), L-threonine, and N-hydroxyhistamine, to compete with host cells for
      iron. Genes that are involved in the production and transport of acinetobactin
      are clustered within the genome of A. baumannii. A recent study showed that entA,
      located outside of the acinetobactin gene cluster, plays important roles in the
      biosynthesis of the acinetobactin precursor DHBA and in bacterial pathogenesis.
      Therefore, understanding the genes that are associated with the biosynthesis and
      transport of acinetobactin in the bacterial genome is required. This review is
      intended to provide a general overview of the genes in the genome of A. baumannii
      that are required for acinetobactin biosynthesis and transport. 

PMID- 25873847
TI  - An Ontology-Based GIS for Genomic Data Management of Rumen Microbes.
AB  - During recent years, there has been exponential growth in biological information.
      With the emergence of large datasets in biology, life scientists are encountering
      bottlenecks in handling the biological data. This study presents an integrated
      geographic information system (GIS)-ontology application for handling microbial
      genome data. The application uses a linear referencing technique as one of the
      GIS functionalities to represent genes as linear events on the genome layer,
      where users can define/change the attributes of genes in an event table and
      interactively see the gene events on a genome layer. Our application adopted
      ontology to portray and store genomic data in a semantic framework, which
      facilitates data-sharing among biology domains, applications, and experts. The
      application was developed in two steps. In the first step, the genome annotated
      data were prepared and stored in a MySQL database. The second step involved the
      connection of the database to both ArcGIS and Protege as the GIS engine and
      ontology platform, respectively. We have designed this application specifically
      to manage the genome-annotated data of rumen microbial populations. Such a GIS
      ontology application offers powerful capabilities for visualizing, managing,
      reusing, sharing, and querying genome-related data. 

PMID- 25873848
TI  - Comparative Modeling and Molecular Dynamics Simulation of Substrate Binding in
      Human Fatty Acid Synthase: Enoyl Reductase and beta-Ketoacyl Reductase Catalytic
      Domains.
AB  - Fatty acid synthase (FASN, EC 2.3.1.85), is a multi-enzyme dimer complex that
      plays a critical role in lipogenesis. This lipogenic enzyme has gained importance
      beyond its physiological role due to its implications in several clinical
      conditions-cancers, obesity, and diabetes. This has made FASN an attractive
      pharmacological target. Here, we have attempted to predict the theoretical models
      for the human enoyl reductase (ER) and beta-ketoacyl reductase (KR) domains based
      on the porcine FASN crystal structure, which was the structurally closest
      template available at the time of this study. Comparative modeling methods were
      used for studying the structure-function relationships. Different validation
      studies revealed the predicted structures to be highly plausible. The respective
      substrates of ER and KR domains-namely, trans-butenoyl and beta-ketobutyryl-were
      computationally docked into active sites using Glide in order to understand the
      probable binding mode. The molecular dynamics simulations of the apo and holo
      states of ER and KR showed stable backbone root mean square deviation
      trajectories with minimal deviation. Ramachandran plot analysis showed 96.0% of
      residues in the most favorable region for ER and 90.3% for the KR domain,
      respectively. Thus, the predicted models yielded significant insights into the
      substrate binding modes of the ER and KR catalytic domains and will aid in
      identifying novel chemical inhibitors of human FASN that target these domains. 

PMID- 25873849
TI  - Mallory-Weiss Tear during Esophagogastroduodenoscopy.
AB  - Mallory-Weiss tears (MWTs) are mucosal lacerations caused by forceful retching
      and are typically located at the gastroesophageal junction. Reported cases of MWT
      with serious complications seen in esophagogastroduodenoscopy are limited. We
      report MWT in an 81-year-old woman who presented with gastric perforation by
      esophagogastroduodenoscopy. We discuss and indicate that hiatal hernia, atrophic
      gastritis and old age may be associated with the gastric perforation in
      comparison to typical tears occurring at the gastroesophageal junction. 

PMID- 25873850
TI  - Spontaneous hepaticoduodenal and choledochoduodenal fistula mimicking duodenal
      ulcer perforation, a very rare complication of transarterial chemoembolization.
AB  - Spontaneous bilo-enteric fistula is a rare complication following surgery or some
      therapeutic interventions such as transarterial chemoembolization (TACE). The
      present case was a young man, a known case of chronic hepatitis B with multiple
      recurrent hepatocellular carcinoma, who presented with clinical sepsis and
      jaundice. Computed tomography showed dilated proximal left intrahepatic ducts
      which suspected anastomotic stricture. He underwent endoscopic retrograde
      cholangiopancreatography, but the endoscopic view showed a deep ulcer covered by
      yellowish debris tissue. After re-evaluation it was found to be
      hepaticoduodenostomy and choledochoduodenostomy tracts. In the present case the
      fistula was suspected to be related to a previous TACE procedure. 

PMID- 25873851
TI  - Environmental insults in early life and submissiveness later in life in mouse
      models.
AB  - Dominant and subordinate dispositions are not only determined genetically but
      also nurtured by environmental stimuli during neuroendocrine development.
      However, the relationship between early life environment and dominance behavior
      remains elusive. Using the IntelliCage-based competition task for group-housed
      mice, we have previously described two cases in which environmental insults
      during the developmental period altered the outcome of dominance behavior later
      in life. First, mice that were repeatedly isolated from their mother and their
      littermates (early deprivation; ED), and second, mice perinatally exposed to an
      environmental pollutant, dioxin, both exhibited subordinate phenotypes, defined
      by decreased occupancy of limited resource sites under highly competitive
      circumstances. Similar alterations found in the cortex and limbic area of these
      two models are suggestive of the presence of neural systems shared across
      generalized dominance behavior. 

PMID- 25873852
TI  - The role of simulation in intertemporal choices.
AB  - One route to understanding the thoughts and feelings of others is by mentally
      putting one's self in their shoes and seeing the world from their perspective,
      i.e., by simulation. Simulation is potentially used not only for inferring how
      others feel, but also for predicting how we ourselves will feel in the future.
      For instance, one might judge the worth of a future reward by simulating how much
      it will eventually be enjoyed. In intertemporal choices between smaller immediate
      and larger delayed rewards, it is observed that as the length of delay increases,
      delayed rewards lose subjective value; a phenomenon known as temporal
      discounting. In this article, we develop a theoretical framework for the
      proposition that simulation mechanisms involved in empathizing with others also
      underlie intertemporal choices. This framework yields a testable psychological
      account of temporal discounting based on simulation. Such an account, if
      experimentally validated, could have important implications for how simulation
      mechanisms are investigated, and makes predictions about special populations
      characterized by putative deficits in simulating others. 

PMID- 25873853
TI  - Enhanced disease characterization through multi network functional normalization
      in fMRI.
AB  - Conventionally, structural topology is used for spatial normalization during the
      pre-processing of fMRI. The co-existence of multiple intrinsic networks which can
      be detected in the resting brain are well-studied. Also, these networks exhibit
      temporal and spatial modulation during cognitive task vs. rest which shows the
      existence of common spatial excitation patterns between these identified
      networks. Previous work (Khullar et al., 2011) has shown that structural and
      functional data may not have direct one-to-one correspondence and functional
      activation patterns in a well-defined structural region can vary across subjects
      even for a well-defined functional task. The results of this study and the
      existence of the neural activity patterns in multiple networks motivates us to
      investigate multiple resting-state networks as a single fusion template for
      functional normalization for multi groups of subjects. We extend the previous
      approach (Khullar et al., 2011) by co-registering multi group of subjects
      (healthy control and schizophrenia patients) and by utilizing multiple resting
      state networks (instead of just one) as a single fusion template for functional
      normalization. In this paper we describe the initial steps toward using multiple
      resting-state networks as a single fusion template for functional normalization.
      A simple wavelet-based image fusion approach is presented in order to evaluate
      the feasibility of combining multiple functional networks. Our results showed
      improvements in both the significance of group statistics (healthy control and
      schizophrenia patients) and the spatial extent of activation when a multiple
      resting-state network applied as a single fusion template for functional
      normalization after the conventional structural normalization. Also, our results
      provided evidence that the improvement in significance of group statistics lead
      to better accuracy results for classification of healthy controls and
      schizophrenia patients. 

PMID- 25873854
TI  - Morphological alterations in the caudate, putamen, pallidum, and thalamus in
      Parkinson's disease.
AB  - Like many neurodegenerative diseases, the clinical symptoms of Parkinsons disease
      (PD) do not manifest until significant progression of the disease has already
      taken place, motivating the need for sensitive biomarkers of the disease. While
      structural imaging is a potentially attractive method due to its widespread
      availability and non-invasive nature, global morphometric measures (e.g., volume)
      have proven insensitive to subtle disease change. Here we use individual surface
      displacements from deformations of an average surface model to capture disease
      related changes in shape of the subcortical structures in PD. Data were obtained
      from both the University of British Columbia (UBC) [n = 54 healthy controls (HC)
      and n = 55 Parkinsons disease (PD) patients] and the publicly available
      Parkinsons Progression Markers Initiative (PPMI) [n = 137 (HC) and n = 189 (PD)]
      database. A high dimensional non-rigid registration algorithm was used to
      register target segmentation labels (caudate, putamen, pallidum, and thalamus) to
      a set of segmentation labels defined on the average-template. The vertex-wise
      surface displacements were significantly different between PD and HC in thalamic
      and caudate structures. However, overall displacements did not correlate with
      disease severity, as assessed by the Unified Parkinson's Disease Rating Scale
      (UPDRS). The results from this study suggest disease-relevant shape abnormalities
      can be robustly detected in subcortical structures in PD. Future studies will be
      required to determine if shape changes in subcortical structures are seen in the
      prodromal phases of the disease. 

PMID- 25873855
TI  - Transfer of conflict and cooperation from experienced games to new games: a
      connectionist model of learning.
AB  - The question of whether, and if so how, learning can be transfered from
      previously experienced games to novel games has recently attracted the attention
      of the experimental game theory literature. Existing research presumes that
      learning operates over actions, beliefs or decision rules. This study instead
      uses a connectionist approach that learns a direct mapping from game payoffs to a
      probability distribution over own actions. Learning is operationalized as a
      backpropagation rule that adjusts the weights of feedforward neural networks in
      the direction of increasing the probability of an agent playing a myopic best
      response to the last game played. One advantage of this approach is that it
      expands the scope of the model to any possible n * n normal-form game allowing
      for a comprehensive model of transfer of learning. Agents are exposed to games
      drawn from one of seven classes of games with significantly different strategic
      characteristics and then forced to play games from previously unseen classes. I
      find significant transfer of learning, i.e., behavior that is path-dependent, or
      conditional on the previously seen games. Cooperation is more pronounced in new
      games when agents are previously exposed to games where the incentive to
      cooperate is stronger than the incentive to compete, i.e., when individual
      incentives are aligned. Prior exposure to Prisoner's dilemma, zero-sum and
      discoordination games led to a significant decrease in realized payoffs for all
      the game classes under investigation. A distinction is made between superficial
      and deep transfer of learning both-the former is driven by superficial payoff
      similarities between games, the latter by differences in the incentive structures
      or strategic implications of the games. I examine whether agents learn to play
      the Nash equilibria of games, how they select amongst multiple equilibria, and
      whether they transfer Nash equilibrium behavior to unseen games. Sufficient
      exposure to a strategically heterogeneous set of games is found to be a necessary
      condition for deep learning (and transfer) across game classes. Paradoxically,
      superficial transfer of learning is shown to lead to better outcomes than deep
      transfer for a wide range of game classes. The simulation results corroborate
      important experimental findings with human subjects, and make several novel
      predictions that can be tested experimentally. 

PMID- 25873856
TI  - The neural milieu of the developing choroid plexus: neural stem cells, neurons
      and innervation.
AB  - The choroid plexus produces cerebrospinal fluid and plays an important role in
      brain homeostasis both pre and postnatally. In vitro studies have suggested that
      cells from adult choroid plexus have stem/progenitor cell-like properties. Our
      initial aim was to investigate whether such a cell population is present in vivo
      during development of the choroid plexus, focusing mainly on the chick choroid
      plexus. Cells expressing neural markers were indeed present in the choroid plexus
      of chick and also those of rodent and human embryos, both within their epithelium
      and mesenchyme. beta3-tubulin-positive cells with neuronal morphology could be
      detected as early as at E8 in chick choroid plexus and their morphological
      complexity increased with development. Whole mount immunochemistry demonstrated
      the presence of neurons throughout choroid plexus development and they appeared
      to be mainly catecholaminergic, as indicated by tyrosine-hydroxylase reactivity.
      The presence of cells co-labeling for BrdU and the neuroblast marker,
      doublecortin, in organotypic choroid plexus cultures supported the hypothesis
      that neurogenesis can occur from neural precursors within the developing choroid
      plexus. Furthermore, we found that extrinsic innervation is present in the
      developing choroid plexus, unlike previously suggested. Altogether, our data are
      consistent with the presence of neural progenitors within the choroid plexus,
      suggest that at least some of the choroid plexus neurons are born locally, and
      show for the first time that choroid plexus innervation occurs prenatally. Hence,
      we propose the existence of a complex neural regulatory network within the
      developing choroid plexus that may play a crucial role in modulating its function
      during development as well as throughout life. 

PMID- 25873857
TI  - Event-driven contrastive divergence: neural sampling foundations.

PMID- 25873858
TI  - Functional role of delta and theta band oscillations for auditory feedback
      processing during vocal pitch motor control.
AB  - The answer to the question of how the brain incorporates sensory feedback and
      links it with motor function to achieve goal-directed movement during
      vocalization remains unclear. We investigated the mechanisms of voice pitch motor
      control by examining the spectro-temporal dynamics of EEG signals when non
      musicians (NM), relative pitch (RP), and absolute pitch (AP) musicians maintained
      vocalizations of a vowel sound and received randomized +/- 100 cents pitch-shift
      stimuli in their auditory feedback. We identified a phase-synchronized (evoked)
      fronto-central activation within the theta band (5-8 Hz) that temporally
      overlapped with compensatory vocal responses to pitch-shifted auditory feedback
      and was significantly stronger in RP and AP musicians compared with non
      musicians. A second component involved a non-phase-synchronized (induced) frontal
      activation within the delta band (1-4 Hz) that emerged at approximately 1 s after
      the stimulus onset. The delta activation was significantly stronger in the NM
      compared with RP and AP groups and correlated with the pitch rebound error (PRE),
      indicating the degree to which subjects failed to re-adjust their voice pitch to
      baseline after the stimulus offset. We propose that the evoked theta is a
      neurophysiological marker of enhanced pitch processing in musicians and reflects
      mechanisms by which humans incorporate auditory feedback to control their voice
      pitch. We also suggest that the delta activation reflects adaptive neural
      processes by which vocal production errors are monitored and used to update the
      state of sensory-motor networks for driving subsequent vocal behaviors. This
      notion is corroborated by our findings showing that larger PREs were associated
      with greater delta band activity in the NM compared with RP and AP groups. These
      findings provide new insights into the neural mechanisms of auditory feedback
      processing for vocal pitch motor control. 

PMID- 25873859
TI  - Inflammation and neuronal plasticity: a link between childhood trauma and
      depression pathogenesis.
AB  - During the past two decades, there has been increasing interest in understanding
      and characterizing the role of inflammation in major depressive disorder (MDD).
      Indeed, several are the evidences linking alterations in the inflammatory system
      to Major Depression, including the presence of elevated levels of pro
      inflammatory cytokines, together with other mediators of inflammation. However,
      it is still not clear whether inflammation represents a cause or whether other
      factors related to depression result in these immunological effects. Regardless,
      exposure to early life stressful events, which represent a vulnerability factor
      for the development of psychiatric disorders, act through the modulation of
      inflammatory responses, but also of neuroplastic mechanisms over the entire life
      span. Indeed, early life stressful events can cause, possibly through epigenetic
      changes that persist over time, up to adulthood. Such alterations may concur to
      increase the vulnerability to develop psychopathologies. In this review we will
      discuss the role of inflammation and neuronal plasticity as relevant processes
      underlying depression development. Moreover, we will discuss the role of
      epigenetics in inducing alterations in inflammation-immune systems as well as
      dysfunction in neuronal plasticity, thus contributing to the long-lasting
      negative effects of stressful life events early in life and the consequent
      enhanced risk for depression. Finally we will provide an overview on the
      potential role of inflammatory system to aid diagnosis, predict treatment
      response, enhance treatment matching, and prevent the onset or relapse of Major
      Depression. 

PMID- 25873861
TI  - Human pluripotent stem cell derived midbrain PITX3(eGFP/w) neurons: a versatile
      tool for pharmacological screening and neurodegenerative modeling.
AB  - PITX3 expression is confined to adult midbrain dopaminergic (mDA) neurons. In
      this study we describe the generation and basic functional characteristics of mDA
      neurons derived from a human pluripotent stem cell (hPSC) line expressing eGFP
      under the control of the PITX3 promoter. Flow cytometry showed that eGFP was
      evident in 15% of the neuron population at day 12 of differentiation and this
      level was maintained until at least day 80. From days 20 to 80 of differentiation
      intracellular chloride decreased and throughout this period around ~20% of
      PITX3(eGFP/w) neurons exhibited spontaneous Ca(2+) transients (from 3.3 +/- 0.3
      to 5.0 +/- 0.1 min(-1), respectively). These neurons also responded to any of
      ATP, glutamate, acetylcholine, or noradrenaline with elevations of intracellular
      calcium. As neuronal cultures matured more dopamine was released and single
      PITX3(eGFP/w) neurons began to respond to more than one neurotransmitter. MPP(+)
      and tumor necrosis factor (TNF), but not prostaglandin E2, caused death of the
      ~50% of PITX3(eGFP/w) neurons (day 80). Tracking eGFP using time lapse confocal
      microscopy over 24 h demonstrated significant TNF-mediated neurite retraction
      over time. This work now shows that these PITX3(eGFP/w) neurons are amenable to
      flow cytometry, release dopamine and respond to multiple neurotransmitters with
      elevations of intracellular calcium, we believe that they represent a versatile
      system for neuropharmacological and neurotoxicological studies. 

PMID- 25873860
TI  - Molecular regulation of auditory hair cell death and approaches to protect
      sensory receptor cells and/or stimulate repair following acoustic trauma.
AB  - Loss of auditory sensory hair cells (HCs) is the most common cause of hearing
      loss. This review addresses the signaling pathways that are involved in the
      programmed and necrotic cell death of auditory HCs that occur in response to
      ototoxic and traumatic stressor events. The roles of inflammatory processes,
      oxidative stress, mitochondrial damage, cell death receptors, members of the
      mitogen-activated protein kinase (MAPK) signal pathway and pro- and anti-cell
      death members of the Bcl-2 family are explored. The molecular interaction of
      these signal pathways that initiates the loss of auditory HCs following acoustic
      trauma is covered and possible therapeutic interventions that may protect these
      sensory HCs from loss via apoptotic or non-apoptotic cell death are explored. 

PMID- 25873862
TI  - Changes in the regulation of the Notch signaling pathway are temporally
      correlated with regenerative failure in the mouse cochlea.
AB  - Sensorineural hearing loss is most commonly caused by the death of hair cells in
      the organ of Corti, and once lost, mammalian hair cells do not regenerate. In
      contrast, other vertebrates such as birds can regenerate hair cells by
      stimulating division and differentiation of neighboring supporting cells. We
      currently know little of the genetic networks which become active in supporting
      cells when hair cells die and that are activated in experimental models of hair
      cell regeneration. Several studies have shown that neonatal mammalian cochlear
      supporting cells are able to trans-differentiate into hair cells when cultured in
      conditions in which the Notch signaling pathway is blocked. We now show that the
      ability of cochlear supporting cells to trans-differentiate declines
      precipitously after birth, such that supporting cells from six-day-old mouse
      cochlea are entirely unresponsive to a blockade of the Notch pathway. We show
      that this trend is seen regardless of whether the Notch pathway is blocked with
      gamma secretase inhibitors, or by antibodies against the Notch1 receptor,
      suggesting that the action of gamma secretase inhibitors on neonatal supporting
      cells is likely to be by inhibiting Notch receptor cleavage. The loss of
      responsiveness to inhibition of the Notch pathway in the first postnatal week is
      due in part to a down-regulation of Notch receptors and ligands, and we show that
      this down-regulation persists in the adult animal, even under conditions of noise
      damage. Our data suggest that the Notch pathway is used to establish the
      repeating pattern of hair cells and supporting cells in the organ of Corti, but
      is not required to maintain this cellular mosaic once the production of hair
      cells and supporting cells is completed. Our results have implications for the
      proposed used of Notch pathway inhibitors in hearing restoration therapies. 

PMID- 25873863
TI  - Defective microglial development in the hippocampus of Cx3cr1 deficient mice.
AB  - Microglial cells participate in brain development and influence neuronal loss and
      synaptic maturation. Fractalkine is an important neuronal chemokine whose
      expression increases during development and that can influence microglia function
      via the fractalkine receptor, CX3CR1. Mice lacking Cx3cr1 show a variety of
      neuronal defects thought to be the result of deficient microglia function.
      Activation of CX3CR1 is important for the proper migration of microglia to sites
      of injury and into the brain during development. However, little is known about
      how fractalkine modulates microglial properties during development. Here we
      examined microglial morphology, response to ATP, and K(+) current properties in
      acute brain slices from Cx3cr1 knockout mice across postnatal hippocampal
      development. We found that fractalkine signaling is necessary for the development
      of several morphological and physiological features of microglia. Specifically,
      we found that the occurrence of an outward rectifying K(+) current, typical of
      activated microglia, that peaked during the second and third postnatal week, was
      reduced in Cx3cr1 knockout mice. Fractalkine signaling also influenced microglial
      morphology and ability to extend processes in response to ATP following its focal
      application to the slice. Our results reveal the developmental profile of several
      morphological and physiological properties of microglia and demonstrate that
      these processes are modulated by fractalkine signaling. 

PMID- 25873864
TI  - Inhibitory properties underlying non-monotonic input-output relationship in low
      frequency spherical bushy neurons of the gerbil.
AB  - Spherical bushy cells (SBCs) of the anteroventral cochlear nucleus (AVCN) receive
      input from large excitatory auditory nerve (AN) terminals, the endbulbs of Held,
      and mixed glycinergic/GABAergic inhibitory inputs. The latter have sufficient
      potency to block action potential firing in vivo and in slice recordings.
      However, it is not clear how well the data from slice recordings match the
      inhibition in the intact brain and how it contributes to complex phenomena such
      as non-monotonic rate-level functions (RLF). Therefore, we determined the input
      output relationship of a model SBC with simulated endbulb inputs and a dynamic
      inhibitory conductance constrained by recordings in brain slice preparations of
      hearing gerbils. Event arrival times from in vivo single-unit recordings in
      gerbils, where 70% of SBC showed non-monotonic RLF, were used as input for the
      model. Model output RLFs systematically changed from monotonic to non-monotonic
      shape with increasing strength of tonic inhibition. A limited range of inhibitory
      synaptic properties consistent with the slice data generated a good match between
      the model and recorded RLF. Moreover, tonic inhibition elevated the action
      potentials (AP) threshold and improved the temporal precision of output functions
      in a SBC model with phase-dependent input conductance. We conclude that activity
      dependent, summating inhibition contributes to high temporal precision of SBC
      spiking by filtering out weak and poorly timed EPSP. Moreover, inhibitory
      parameters determined in slice recordings provide a good estimate of inhibitory
      mechanisms apparently active in vivo. 

PMID- 25873865
TI  - Yes, there is a medial nucleus of the trapezoid body in humans.
AB  - The medial nucleus of the trapezoid body (MNTB) is a collection of brainstem
      neurons that function within the ascending auditory pathway. MNTB neurons are
      associated with a number of anatomical and physiological specializations which
      make these cells especially well-equipped to provide extremely fast and precise
      glycinergic inhibition to its target neurons in the superior olivary complex and
      ventral nucleus of the lateral lemniscus. The inhibitory influence of MNTB
      neurons plays essentials roles in the localization of sound sources and encoding
      temporal features of complex sounds. The morphology, afferent and efferent
      connections and physiological response properties of MNTB neurons have been well
      characterized in a number of laboratory rodents and some carnivores. Furthermore,
      the MNTB has been positively identified in all mammals examined, ranging from
      opossum and mice to chimpanzees. From the early 1970s through 2009, a number of
      studies denied the existence of the MNTB in humans and consequentially, the
      existence of this nucleus in the human brain has been debated for nearly 50
      years. The absence of the MNTB from the human brain would negate current
      principles of sound localization and would require a number of novel adaptations,
      entirely unique to humans. However, a number of recent studies of human post
      mortem tissue have provided evidence supporting the existence of the MNTB in
      humans. It therefore seems timely to review the structure and function of the
      MNTB, critically review the literature which led to the denial of the human MNTB
      and then review recent investigations supporting the existence of the MNTB in the
      human brain. 

PMID- 25873868
TI  - Comparison of haptic guidance and error amplification robotic trainings for the
      learning of a timing-based motor task by healthy seniors.
AB  - With age, a decline in the temporal aspect of movement is observed such as a
      longer movement execution time and a decreased timing accuracy. Robotic training
      can represent an interesting approach to help improve movement timing among the
      elderly. Two types of robotic training-haptic guidance (HG; demonstrating the
      correct movement for a better movement planning and improved execution of
      movement) and error amplification (EA; exaggerating movement errors to have a
      more rapid and complete learning) have been positively used in young healthy
      subjects to boost timing accuracy. For healthy seniors, only HG training has been
      used so far where significant and positive timing gains have been obtained. The
      goal of the study was to evaluate and compare the impact of both HG and EA
      robotic trainings on the improvement of seniors' movement timing. Thirty-two
      healthy seniors (mean age 68 +/- 4 years) learned to play a pinball-like game by
      triggering a one-degree-of-freedom hand robot at the proper time to make a
      flipper move and direct a falling ball toward a randomly positioned target.
      During HG and EA robotic trainings, the subjects' timing errors were decreased
      and increased, respectively, based on the subjects' timing errors in initiating a
      movement. Results showed that only HG training benefited learning, but the
      improvement did not generalize to untrained targets. Also, age had no influence
      on the efficacy of HG robotic training, meaning that the oldest subjects did not
      benefit more from HG training than the younger senior subjects. Using HG to teach
      the correct timing of movement seems to be a good strategy to improve motor
      learning for the elderly as for younger people. However, more studies are needed
      to assess the long-term impact of HG robotic training on improvement in movement
      timing. 

PMID- 25873866
TI  - Hydration and beyond: neuropeptides as mediators of hydromineral balance, anxiety
      and stress-responsiveness.
AB  - Challenges to body fluid homeostasis can have a profound impact on hypothalamic
      regulation of stress responsiveness. Deficiencies in blood volume or sodium
      concentration leads to the generation of neural and humoral signals relayed
      through the hindbrain and circumventricular organs that apprise the
      paraventricular nucleus of the hypothalamus (PVH) of hydromineral imbalance.
      Collectively, these neural and humoral signals converge onto PVH neurons,
      including those that express corticotrophin-releasing factor (CRF), oxytocin
      (OT), and vasopressin, to influence their activity and initiate compensatory
      responses that alleviate hydromineral imbalance. Interestingly, following
      exposure to perceived threats to homeostasis, select limbic brain regions mediate
      behavioral and physiological responses to psychogenic stressors, in part, by
      influencing activation of the same PVH neurons that are known to maintain body
      fluid homeostasis. Here, we review past and present research examining
      interactions between hypothalamic circuits regulating body fluid homeostasis and
      those mediating behavioral and physiological responses to psychogenic stress. 

PMID- 25873867
TI  - Augmented brain function by coordinated reset stimulation with slowly varying
      sequences.
AB  - Several brain disorders are characterized by abnormally strong neuronal
      synchrony. Coordinated Reset (CR) stimulation was developed to selectively
      counteract abnormal neuronal synchrony by desynchronization. For this, phase
      resetting stimuli are delivered to different subpopulations in a timely
      coordinated way. In neural networks with spike timing-dependent plasticity CR
      stimulation may eventually lead to an anti-kindling, i.e., an unlearning of
      abnormal synaptic connectivity and abnormal synchrony. The spatiotemporal
      sequence by which all stimulation sites are stimulated exactly once is called the
      stimulation site sequence, or briefly sequence. So far, in simulations, pre
      clinical and clinical applications CR was applied either with fixed sequences or
      rapidly varying sequences (RVS). In this computational study we show that
      appropriate repetition of the sequence with occasional random switching to the
      next sequence may significantly improve the anti-kindling effect of CR. To this
      end, a sequence is applied many times before randomly switching to the next
      sequence. This new method is called SVS CR stimulation, i.e., CR with slowly
      varying sequences. In a neuronal network with strong short-range excitatory and
      weak long-range inhibitory dynamic couplings SVS CR stimulation turns out to be
      superior to CR stimulation with fixed sequences or RVS. 

PMID- 25873869
TI  - Audiovisual associations alter the perception of low-level visual motion.
AB  - Motion perception is a pervasive nature of vision and is affected by both
      immediate pattern of sensory inputs and prior experiences acquired through
      associations. Recently, several studies reported that an association can be
      established quickly between directions of visual motion and static sounds of
      distinct frequencies. After the association is formed, sounds are able to change
      the perceived direction of visual motion. To determine whether such rapidly
      acquired audiovisual associations and their subsequent influences on visual
      motion perception are dependent on the involvement of higher-order attentive
      tracking mechanisms, we designed psychophysical experiments using regular and
      reverse-phi random dot motions isolating low-level pre-attentive motion
      processing. Our results show that an association between the directions of low
      level visual motion and static sounds can be formed and this audiovisual
      association alters the subsequent perception of low-level visual motion. These
      findings support the view that audiovisual associations are not restricted to
      high-level attention based motion system and early-level visual motion processing
      has some potential role. 

PMID- 25873870
TI  - Nigral proteasome inhibition in mice leads to motor and non-motor deficits and
      increased expression of Ser129 phosphorylated alpha-synuclein.
AB  - Parkinson's disease is a neurodegenerative disorder characterized by motor and
      non-motor disturbances. Various pathogenic pathways drive disease progression
      including oxidative stress, mitochondrial dysfunction, alpha-synuclein
      aggregation and impairment of protein degradation systems. Dysfunction of the
      ubiquitin-proteasome system in the substantia nigra of Parkinson's disease
      patients is believed to be one of the causes of protein aggregation and cell
      death associated with this disorder. Lactacystin, a potent inhibitor of the
      proteasome, was previously delivered to the nigrostriatal pathway of rodents to
      model nigrostriatal degeneration. Although lactacystin-treated animals develop
      parkinsonian motor impairment, it is currently unknown whether they also develop
      non-motor symptoms characteristic of this disorder. In order to further describe
      the proteasome inhibition model of Parkinson's disease, we characterized the
      unilateral lactacystin model, performed by stereotaxic injection of the toxin in
      the substantia nigra of mice. We studied the degree of neurodegeneration and the
      behavioral phenotype 1 and 3 weeks after lactacystin lesion both in terms of
      motor impairment, as well as non-motor symptoms. We report that unilateral
      administration of 3 MUg lactacystin to the substantia nigra of mice leads to
      partial (~40%) dopaminergic cell loss and concurrent striatal dopamine depletion,
      accompanied by increased expression of Ser129-phosphorylated alpha-synuclein.
      Behavioral characterization of the model revealed parkinsonian motor impairment,
      as well as signs of non-motor disturbances resembling early stage Parkinson's
      disease including sensitive and somatosensory deficits, anxiety-like behavior,
      and perseverative behavior. The consistent finding of good face validity,
      together with relevant construct validity, warrant a further evaluation of
      proteasome inhibition models of Parkinson's disease in pre-clinical research and
      validation of therapeutic targets. 

PMID- 25873872
TI  - Two dopamine receptors play different roles in phase change of the migratory
      locust.
AB  - The migratory locust, Locusta migratoria, shows remarkable phenotypic plasticity
      at behavioral, physiological, and morphological levels in response to fluctuation
      in population density. Our previous studies demonstrated that dopamine (DA) and
      the genes in the dopamine metabolic pathway mediate phase change in Locusta.
      However, the functions of different dopamine receptors in modulating locust phase
      change have not been fully explored. In the present study, DA concentration in
      the brain increased during crowding and decreased during isolation. The
      expression level of dopamine receptor 1 (Dop1) increased from 1 to 4 h of
      crowding, but remained unchanged during isolation. Injection of Dop1 agonist
      SKF38393 into the brains of solitary locusts promoted gregarization, induced
      conspecific attraction-response and increased locomotion. RNAi knockdown of Dop1
      and injection of antagonist SCH23390 in gregarious locusts induced solitary
      behavior, promoted the shift to repulsion-response and reduced locomotion. By
      contrast, the expression level of dopamine receptor 2 (Dop2) gradually increased
      during isolation, but remained stable during crowding. During the isolation of
      gregarious locusts, injection of Dop2 antagonist S(-)-sulpiride or RNAi knockdown
      of Dop2 inhibited solitarization, maintained conspecific attraction-response and
      increased locomotion; by comparison, the isolated controls displayed conspecific
      repulsion-response and weaker motility. Activation of Dop2 in solitary locusts
      through injection of agonist, R(-)-TNPA, did not affect their behavioral state.
      Thus, DA-Dop1 signaling in the brain of Locusta induced the gregariousness,
      whereas DA-Dop2 signaling mediated the solitariness. Our study demonstrated that
      Dop1 and Dop2 modulated locust phase change in two different directions. Further
      investigation of Locusta Dop1 and Dop2 functions in modulating phase change will
      improve our understanding of the molecular mechanism underlying phenotypic
      plasticity in locusts. 

PMID- 25873871
TI  - Combined neuromodulatory interventions in acute experimental pain: assessment of
      melatonin and non-invasive brain stimulation.
AB  - Transcranial direct current stimulation (tDCS) and melatonin can effectively
      treat pain. Given their potentially complementary mechanisms of action, their
      combination could have a synergistic effect. Thus, we tested the hypothesis that
      compared to the control condition and melatonin alone, tDCS combined with
      melatonin would have a greater effect on pain modulatory effect, as assessed by
      quantitative sensory testing (QST) and by the pain level during the Conditioned
      Pain Modulation (CPM)-task. Furthermore, the combined treatment would have a
      greater cortical excitability effect as indicated by the transcranial magnetic
      stimulation (TMS) and on the serum BDNF level. Healthy males (n = 20), (aged 18
      40 years), in a blinded, placebo-controlled, crossover, clinical trial, were
      randomized into three groups: sublingual melatonin (0.25 mg/kg) + a-tDCS,
      melatonin (0.25 mg/kg) + sham-(s)-tDCS, or sublingual placebo+sham-(s)-tDCS.
      Anodal stimulation (2 mA, 20 min) was applied over the primary motor cortex.
      There was a significant difference in the heat pain threshold ( degrees C) for
      melatonin+a-tDCS vs. placebo+s-tDCS (mean difference: 4.86, 95% confidence
      interval [CI]: 0.9 to 8.63) and melatonin+s-tDCS vs. placebo+s-tDCS (mean: 5.16,
      95% CI: 0.84 to 8.36). There was no difference between melatonin+s-tDCS and
      melatonin+a-tDCS (mean difference: 0.29, 95% CI: -3.72 to 4.23). The mean change
      from the baseline on amplitude of motor evocate potential (MEP) was significantly
      higher in the melatonin+a-tDCS (-19.96% +/- 5.2) compared with melatonin+s-tDCS
      group (-1.36% +/- 5.35) and with placebo+s-tDCS group (3.61% +/- 10.48),
      respectively (p < 0.05 for both comparisons). While melatonin alone or combined
      with a-tDCS did not significantly affect CPM task result, and serum BDNF level.
      The melatonin effectively reduced pain; however, its association with a-tDCS did
      not present an additional modulatory effect on acute induced pain. 

PMID- 25873874
TI  - Tinea pedis presenting as asymmetric purpuric papules on the sole of the foot: a
      case report.
AB  - In this report we describe a unique case of tinea pedis. A 29-year-old man
      presented with a 3-day history of asymptomatic purpuric papules predominantly on
      his left foot. Potassium hydroxide preparation demonstrated fungal hyphae and
      culture yielded Trichophyton mentagrophytes. This patient presented unusually
      with purpuric papules, unlike the three commonly described types of tinea pedis.
      Given the morphology, positive potassium hydroxide slide preparation, T.
      mentagrophytes on fungal culture and clinical response to ketoconazole cream, we
      conclude that this represents a unique variant of tinea pedis. We recognize that
      even common dermatological diagnoses can have unique presentations, and it is
      important for clinicians to maintain a broad differential for new dermatologic
      cases. 

PMID- 25873873
TI  - A critical review of the neuroimaging literature on synesthesia.
AB  - Synesthesia refers to additional sensations experienced by some people for
      specific stimulations, such as the systematic arbitrary association of colors to
      letters for the most studied type. Here, we review all the studies (based mostly
      on functional and structural magnetic resonance imaging) that have searched for
      the neural correlates of this subjective experience, as well as structural
      differences related to synesthesia. Most differences claimed for synesthetes are
      unsupported, due mainly to low statistical power, statistical errors, and
      methodological limitations. Our critical review therefore casts some doubts on
      whether any neural correlate of the synesthetic experience has been established
      yet. Rather than being a neurological condition (i.e., a structural or functional
      brain anomaly), synesthesia could be reconsidered as a special kind of childhood
      memory, whose signature in the brain may be out of reach with present brain
      imaging techniques. 

PMID- 25873875
TI  - Immunohistochemical Similarities between Lichen Sclerosus et Atrophicus and
      Morphea: A Case Study.
AB  - Both morphea and lichen sclerosus et atrophicus (LSA) are connective tissue
      diseases that mainly affect the skin. A recent report suggested that a
      substantial portion of morphea coexists with LSA. In this report, we describe a
      case of LSA on the abdomen accompanied by morphea; we employed
      immunohistochemical staining for periostin as well as MMP-7 and MMP-28, both of
      which are reported to facilitate fibrosis in the development of various organs,
      including skin. To our knowledge, this is first English language paper that
      demonstrates the immunohistochemical staining of periostin, MMP-7 and MMP-28 for
      morphea and LSA. Our present case might suggest possible mechanisms for the
      coexistence of two different sclerotic skin disorders. 

PMID- 25873876
TI  - Dose-reduced trastuzumab emtansine: active and safe in acute hepatic dysfunction.
AB  - Breast cancer is the most common cancer in women worldwide. The majority of
      deaths attributed to breast cancer are a result of metastatic disease, and 30% of
      early breast cancers (EBC) will develop distant disease. The 5-year survival of
      patients with metastatic disease is estimated at 23%. Breast cancer subtypes
      continue to be stratified histologically on oestrogen, progesterone and human
      epidermal growth factor-2 (HER2) receptor expression. HER2-positive breast
      cancers represent 25% of all breast cancer diagnoses. The therapies available for
      metastatic breast cancer (MBC) are expanding, in particular within the field of
      HER2-positive disease, with the approval of trastuzumab, pertuzumab, lapatinib
      and trastuzumab emtansine (TDM-1). Recently, TDM-1 has been shown to improve
      progression-free survival in HER2 MBC when compared to capecitabine and lapatinib
      in clinical studies. Its main toxicities are deranged liver function tests and
      thrombocytopenia. There have also been cases of acute liver failure. Therefore,
      its use in acute hepatic dysfunction, to our knowledge, has been neither studied
      nor reported. We report a patient with progressive HER2-positive MBC who had
      previously responded to multiple HER2-targeted therapies that presented with
      acute hepatic dysfunction. She was treated with dose-reduced TDM-1 safely, with
      clear evidence of rapid biochemical, clinical and radiological response. This
      allowed dose escalation of TDM-1, and the patient maintains an ongoing response. 

PMID- 25873877
TI  - Successful nilotinib treatment in a child with chronic myeloid leukemia.
AB  - A 16-year-old female was diagnosed incedentally with chronic myeloid leukemia
      (CML) in the chronic phase. She showed complete remission after 3 months of
      nilotinib treatment. CML is a rare malignant neoplasm in pediatric age. It is
      characterized by a Philadelphia chromosome, which comes from a genetic
      translocation between chromosomes 9 and 22. This translocation results in an
      abnormal fusion called BCR-ABL oncogene which encodes a chimeric BCR-ABL protein.
      This protein is the underlying cause of CML. Nilotinib is a newly licensed drug
      for CML in adults. Structurally, it is similar to imatinib (the older tyrosine
      kinase inhibitor), but it is much more potent in inhibiting BCR-ABL due to its
      much increased affinity for its binding site. Specific guidelines for CML
      treatment in children have yet to be determined. In our patient, nilotinib was
      used as an off-label drug because it is not licensed for children. According to
      the pharmacokinetic response to drugs, children cannot be considered small adults
      irrespective of their weight. Off-label drug use based on evidence that it is the
      best treatment available is an important tool in the hands of expert treating
      physicians. 

PMID- 25873878
TI  - Primary synovial cell sarcoma of the kidney: case report and review of the
      literature.
AB  - Synovial cell sarcoma (SCS) of the kidney is a rare tumor entity with a poor
      prognosis. Morphologic and immunohistochemical characteristics may overlap with
      other more common neoplasms of the kidney. Therefore, the diagnosis of primary
      renal SCS not only requires the exclusion of similar tumor types, but also a
      confirmation of SYT-SSX gene fusion using molecular techniques. The treatment
      comprises radical surgery, and, depending on age and health status, adjuvant
      chemotherapy in selected patients. Here, we present an elderly SCS patient in
      whom straightforward radical surgical treatment resulted in a sustained complete
      remission; it allowed us to perform a literature survey focusing on current
      diagnostic tools for SCS. 

PMID- 25873879
TI  - Testicular metastasis in a case of squamous cell carcinoma of the lung.
AB  - Testicular metastases are a rare finding. Typically, a testicular metastasis will
      present as a complication of progressive disease or as a primary sign of
      malignancy. Excluding lymphoma and leukemia, prostate cancer is the most common
      primary site that metastasizes to the testes. Testicular metastases resulting
      from squamous cell carcinoma of the lung have rarely been reported in previous
      literature. Here, we report a case of stage IV squamous cell carcinoma of the
      lung with metastases to the brain and multiple bilateral lung lesions. Following
      palliative systemic chemotherapy, this patient was found to have a right
      testicular mass. Pathology reports confirmed that this was a testicular
      metastasis of squamous cell lung carcinoma origin. 

PMID- 25873880
TI  - Severe Generalized Weakness, Paralysis, and Aphasia following Administration of
      Irinotecan and Oxaliplatin during FOLFIRINOX Chemotherapy.
AB  - BACKGROUND: Irinotecan is commonly used in combination with oxaliplatin as a
      component of FOLFIRINOX chemotherapy for several gastrointestinal malignancies.
      The purpose of this case report is to describe a patient who developed acute
      paralysis and aphasia while receiving her initial infusion of irinotecan. CASE
      REPORT: A 67-year-old woman with newly diagnosed metastatic pancreatic
      adenocarcinoma presented for her first cycle of FOLFIRINOX chemotherapy. During
      her infusion of irinotecan, she developed acute onset of generalized weakness,
      paralysis of all extremities, and nonfluent aphasia with complete inability to
      communicate. This episode was self-limited and resolved within 2 h. Prior to
      subsequent infusions she received intravenous repletion of potassium and had no
      recurrence of symptoms. DISCUSSION: In selected cases, coadministration of
      irinotecan and oxaliplatin may result in severe generalized weakness and aphasia,
      which may be triggered by underlying electrolyte disturbances. Careful monitoring
      and correction of potassium may help prevent this reaction.

PMID- 25873881
TI  - Squamous carcinoma of the lung presenting as migraine-type headache: a case
      report.
AB  - INTRODUCTION: Orthostatic hypotension has long been recognised as a
      paraneoplastic effect of lung cancer. Lung cancer presenting with orthostatic
      hypotension and migraine-type headaches has not been previously described in the
      literature. CASE REPORT: A 62-year-old Caucasian male presented with headaches,
      typical of his migraine, after a 30-year migraine-free period. An examination
      revealed a significant postural drop in BP with reflex tachycardia and no other
      features of dysautonomia. Investigations showed a metastatic squamous cell lung
      cancer. Pharmacological treatment of orthostatic hypotension resolved the
      migraine-type headaches. DISCUSSION: Orthostatic hypotension is associated with
      lung cancer. Prompt pharmacological treatment in patients not responding to non
      pharmacological therapy can provide relief from disabling symptoms of orthostatic
      hypotension. In this patient, this included symptoms consistent with migraine
      type headaches.

PMID- 25873882
TI  - Elevated erythropoietin and multicystic neoplasm of the pancreas.
AB  - Cystic lesions of the pancreas are more frequently recognized due to the
      widespread use of improved imaging techniques. There are a variety of pancreatic
      cystic lesions with different clinical presentations and malignant potentials,
      and their management depends on the type of the cysts. Although the early
      recognition of a cystic neoplasm with malignant potential provides an opportunity
      of early surgical treatment, the precise diagnosis of the cystic neoplasm can be
      a challenge, largely due to the lack of reliable biomarkers of malignant
      transformation. We report a case of a large, multicystic neoplasm within the body
      and tail of the pancreas complicated by elevated erythropoietin, which is likely
      related to the malignant transformation of the pancreatic neoplasm. 

PMID- 25873883
TI  - Large cell neuroendocrine carcinoma of the lung with cancer-associated
      retinopathy.
AB  - We report a rare case of large cell neuroendocrine carcinoma (LCNEC) of the lung
      with cancer-associated retinopathy (CAR). To our knowledge, only two cases of
      LCNEC with CAR have been reported, one in 1995 and another in 2013. CAR,
      typically associated with small cell lung cancer (SCLC), is one of the
      paraneoplastic syndromes with deterioration of visual acuity, visual field
      constriction, and photophobia. CAR is caused by an autoimmune system reaction
      against the same antigen in the tumor and retinal photoreceptor cells. To
      diagnose CAR, genetic retinal dystrophies or any other medical causes of
      retinopathy should be excluded, but there are no standard diagnostic criteria.
      Anti-retinal antibodies are known to be positive in CAR patients, and anti
      recoverin antibodies are thought to be sensitive and specific to CAR. In our
      case, anti-recoverin antibodies were not detected by serum tests, but CAR could
      be diagnosed on the basis of ophthalmological findings including clinical
      symptoms, electroretinographic findings, and visual field tests. CAR with
      clinical features of rapid visual disorder should be considered in LCNEC patients
      as well as in SCLC patients. 

PMID- 25873884
TI  - Supratentorial tanycytic ependymoma in an adult male: case report and review of
      literature.
AB  - Ependymomas, tumors of the ependymal cells, are very rare and usually present in
      the pediatric population. Furthermore, there are even rarer variants of
      ependymomas that can include cellular, papillary, clear cell, and tanycytic
      subtypes. We present a case of a supratentorial tanycytic ependymoma in an adult
      male and review the literature in regard to this rare primary central nervous
      system neoplasm. 

PMID- 25873885
TI  - EGFR-Mutated Breast Metastasis of Lung Adenocarcinoma: A Case Report.
AB  - Breast metastasis from other primary carcinoma is very rare and could be
      difficult to identify despite immunohistochemistry analysis. Breast metastasis
      from lung adenocarcinoma can mimic triple-negative breast cancer. Given the
      prognosis and therapeutic challenges, a correct diagnosis appears essential, and
      molecular biomarkers could be useful. We report the case of a 52-year-old woman
      with a breast mass initially diagnosed as primary breast cancer and secondarily
      attached to breast metastasis from an EGFR-mutated lung adenocarcinoma. The same
      activating EGFR mutations were identified in both the primary lung carcinoma and
      the breast metastasis. 

PMID- 25873886
TI  - Aspergillosis superinfection as a cause of death of crizotinib-induced
      interstitial lung disease successfully treated with high-dose corticosteroid
      therapy.
AB  - Crizotinib is an efficacious and well-tolerated drug in the management of ALK
      positive lung cancer. Crizotinib treatment, however, is rarely complicated by the
      occurrence of acute interstitial lung disease (ILD) that is often fatal. There is
      no treatment for this serious adverse event. We report a female non-small cell
      lung cancer patient who developed ILD after a few days of crizotinib therapy. She
      showed a significant improvement after a high dose of pulse corticosteroid
      therapy, both radiologically and clinically. Unfortunately, the patient
      subsequently developed an aspergillosis superinfection leading to death. Our
      experience suggests that high-dose steroid therapy may be efficacious in the
      management of a severe complication of crizotinib therapy. However, potent
      antifungal therapy should be considered to prevent the risk of severe
      aspergillosis. 

PMID- 25873887
TI  - Langerhans cell histiocytosis in an adult with involvement of the calvarium,
      cerebral cortex and brainstem: discussion of pathophysiology and rationale for
      the use of intravenous immune globulin.
AB  - We report a case of Langerhans cell histiocytosis in a 64-year-old male who
      presented with symptoms and signs of brain involvement, including seizures and
      hypopituitarism. The diagnosis was confirmed with a biopsy of a lytic skull
      lesion. The disease affecting the bone showed no sign of progression following a
      short course of cladribine. Signs of temporal lobe involvement led to an
      additional biopsy, which showed signs of nonspecific neurodegeneration and which
      triggered status epilepticus. Lesions noted in the brainstem were typical for the
      paraneoplastic inflammation reported in this condition. These lesions improved
      after treatment with cladribine. They remained stable while on treatment with
      intravenous immune globulin. 

PMID- 25873888
TI  - Balo's Concentric Sclerosis with Acute Presentation and Co-Existing Multiple
      Sclerosis-Typical Lesions on MRI.
AB  - Balo's disease also known as Balo's concentric sclerosis (BCS) is a rare
      demyelinating disorder which is characterized pathologically and radiologically
      by concentric rings of demyelinated and relatively myelin-preserved white matter.
      We describe the case of a 25-year-old female presenting with stroke-like symptoms
      who was diagnosed with BCS on MRI. At clinical onset, she also showed co-existing
      multiple sclerosis (MS)-typical lesions in the brain. This report extends the
      recent concept that BCS may share similar pathogenesis and radiological
      progression as MS lesions, that they may occur simultaneously in the same patient
      and that they may represent different manifestations of the same disease process.
      Also, BCS needs not be a fulminant disease and may often show a benign self
      limiting course as in our case. 

PMID- 25873889
TI  - Basilar artery territory stroke secondary to invasive fungal sphenoid sinusitis:
      a case report and review of the literature.
AB  - BACKGROUND: Mucormycosis is a fungal infection with the following 5 classic
      forms: cutaneous, pulmonary, gastrointestinal, disseminated, and rhinocerebral.
      The rhinocerebral form can be rapidly progressive and invasive with a high
      mortality rate. We present a case of a 38-year-old man with invasive mucormycosis
      that led to a basilar artery territory stroke. Rhinocerebral mucormycosis is an
      unusual cause of stroke. CASE REPORT: A 38-year-old man with a past medical
      history of diabetes mellitus presented with altered mental status. A lumbar
      puncture revealed eosinophilic pleocytosis with a mildly elevated total protein
      and borderline low glucose level. CT revealed a left medullary and cerebellar
      infarct confirmed by MRI. MRI also displayed a diffuse marrow signal abnormality
      in the clivus with contiguous sinus disease. Endoscopic sinus surgery confirmed
      that the fungal sinusitis was mucormycosis of the Rhizopus genus, which had
      affected the left sphenoid sinus, invaded through the skull base, and involved
      the basilar artery. He was given liposomal amphotericin (500 mg i.v.) with
      posaconazole (400 mg i.v. twice daily). Due to the severity of the invasion and
      poor prognosis, the patient was discharged with comfort care measures.
      DISCUSSION: Clinicians should be aware of invasive sinusitis as a rare cause of
      stroke in diabetics. Once the subarachnoid space and basal arteries of the brain
      have been invaded, the prognosis is very poor. The key to improvement of outcomes
      is early recognition and treatment, and examination of the sinuses on
      neuroimaging in all cases of stroke is vital.

PMID- 25873890
TI  - Low dose of clonazepam is effective in the treatment of painless legs and moving
      toes syndrome: a case report.
AB  - INTRODUCTION: Painless legs and moving toes syndrome (PoLMT) is a rare movement
      disorder characterized by flexion, extension, abduction, adduction, and torsion
      of toes in the absence of pain. It is considered a variant of painful legs and
      moving toes syndrome, which is characterized by similar movements but is
      accompanied by pain. Although neuropathy, spinal cord compression, brain tumor,
      cerebral infarction, and Wilson's disease have been reported to be associated
      with PoLMT, the actual cause, trigger, and mechanism remain unclear. Therefore, a
      standardized treatment for PoLMT is not established yet. CASE PRESENTATION: We
      describe a 64-year-old Japanese woman with no past medical history who presented
      with nonrhythmic repetitive involuntary toe movement of the left foot in the
      absence of pain. She was diagnosed with idiopathic PoLMT and treated with a low
      dose of clonazepam (0.5 mg/day). The involuntary movement disappeared completely
      several days after treatment. CONCLUSION: A low dose of clonazepam is effective
      in the treatment of PoLMT.

PMID- 25873891
TI  - Dexamethasone implant (ozurdex) in a case with unilateral simultaneous central
      retinal vein and branch retinal artery occlusion.
AB  - Simultaneous branch retinal artery and vein occlusion is a rare condition that
      may cause severe visual loss, and its treatment is often unrewarding. Herein, we
      report a case with simultaneous central retinal vein and branch retinal artery
      occlusion; it was successfully treated with a single dexamethasone intravitreal
      implant. The affected eye attained a visual acuity level of 20/25 from the visual
      acuity of hand motions at presentation with a residual, but relatively
      diminished, altitudinal scotoma during a follow-up period of 6 months. 

PMID- 25873892
TI  - Corneal Chromoblastomycosis Caused by Fonsecaea pedrosoi.
AB  - PURPOSE: To report 2 unusual cases of fungal keratitis due to Fonsecaea pedrosoi.
      METHODS: Two patients were diagnosed with Fonsecaea pedrosoi keratitis. Their
      files were reviewed for predisposing factors, clinical characteristics,
      microbiological study, treatment, and outcome. RESULTS: Two consecutive patients
      presented with brownish pigmented corneal ulcers in their eyes after sustaining
      eye trauma from vegetative matter. In both cases, corneal scrapings were
      collected for microscopic examination and culture. Dematiaceous hyphae were seen
      on the smears, and dark pigmented colonies grew on the culture media, identified
      as F. pedrosoi. Both patients were treated and cured with combined topical
      antifungal agents and oral itraconazole. The first patient required an amniotic
      membrane patch, while the second received an intracameral amphotericin B
      injection. CONCLUSIONS: Pigmented infiltrates can be an important diagnostic
      clue, but a microscopic evaluation and culture are required to obtain an accurate
      diagnosis of Fonsecaea keratitis. The prompt diagnosis and combined antifungal
      treatment can prevent morbidity associated with this fungal infection.

PMID- 25873893
TI  - Valsalva-like retinopathy spontaneously occurred after ocular massage.
AB  - PURPOSE: The aim of this study is to describe a case of Valsalva-like retinopathy
      that occurred after ocular massage. CASE PRESENTATION: A healthy 44-year-old
      Japanese female had massaged her eye with strong pressure several times.
      Subsequently, she noticed a loss in the left central vision. A left-eye fundus
      examination showed a dense preretinal hemorrhage located under the internal
      limiting membrane at the posterior pole and a mild vitreous hemorrhage. We
      performed a neodymium-doped yttrium-aluminium-garnet laser membranotomy to
      perforate the internal limiting membrane. Her best-corrected visual acuity
      improved from 0.01 to 1.0. No retinal vascular abnormalities in the macular area
      were found. CONCLUSION: Ocular massage can cause Valsalva-like retinopathy.

PMID- 25873894
TI  - Angioarchitectural evolution of clival dural arteriovenous fistulas in two
      patients.
AB  - Dural arteriovenous fistulas (dAVFs) may present in a variety of ways, including
      as carotid-cavernous sinus fistulas. The ophthalmologic sequelae of carotid
      cavernous sinus fistulas are known and recognizable, but less commonly seen is
      the rare clival fistula. Clival dAVFs may have a variety of potential anatomical
      configurations but are defined by the involvement of the venous plexus just
      overlying the bony clivus. Here we present two cases of clival dAVFs that most
      likely evolved from carotid-cavernous sinus fistulas. 

PMID- 25873895
TI  - Urinary beta2-Microglobulin Testing in Pediatric Uveitis: A Case Report of a 9
      Year-Old Boy with Renal and Ocular Sarcoidosis.
AB  - We present here a case of a 9-year-old boy with bilateral anterior uveitis and an
      extremely elevated urinary beta2-microglobulin level (25,400 MUg/l). The normal
      range for urinary excretion of beta2-microglobulin is 0-300 MUg/l. In patients
      with tubulointerstitial nephritis and uveitis syndrome (TINU), elevations
      typically range from 1,260 to 5,160 MUg/l. Renal biopsy was pursued, and
      significant granulomatous interstitial nephritis consistent with sarcoidosis was
      identified. Systemic immune modulation was required for control of ocular
      inflammation. This case highlights the importance of urinary beta2-microglobulin
      testing in the pediatric patient uveitis population, and additionally the need to
      pursue kidney biopsy in the presence of extreme elevations in urinary beta2
      microglobulin to differentiate between TINU and sarcoidosis. 

PMID- 25873896
TI  - A pretargeting system for tumor PET imaging and radioimmunotherapy.
AB  - Labeled antibodies, as well as their fragments and antibody-derived recombinant
      constructs, have long been proposed as general vectors to target radionuclides to
      tumor lesions for imaging and therapy. They have indeed shown promise in both
      imaging and therapeutic applications, but they have not fulfilled the original
      expectations of achieving sufficient image contrast for tumor detection or
      sufficient radiation dose delivered to tumors for therapy. Pretargeting was
      originally developed for tumor immunoscintigraphy. It was assumed that directly
      radiolabled antibodies could be replaced by an unlabeled immunoconjugate capable
      of binding both a tumor-specific antigen and a small molecular weight molecule.
      The small molecular weight molecule would carry the radioactive payload and would
      be injected after the bispecific immunoconjugate. It has been demonstrated that
      this approach does allow for both antibody-specific recognition and fast
      clearance of the radioactive molecule, thus resulting in improved tumor-to-normal
      tissue contrast ratios. It was subsequently shown that pretargeting also held
      promise for tumor therapy, translating improved tumor-to-normal tissue contrast
      ratios into more specific delivery of absorbed radiation doses. Many technical
      approaches have been proposed to implement pretargeting, and two have been
      extensively documented. One is based on the avidin-biotin system, and the other
      on bispecific antibodies binding a tumor-specific antigen and a hapten. Both have
      been studied in preclinical models, as well as in several clinical studies, and
      have shown improved targeting efficiency. This article reviews the historical and
      recent preclinical and clinical advances in the use of bispecific-antibody-based
      pretargeting for radioimmunodetection and radioimmunotherapy of cancer. The
      results of recent evaluation of pretargeting in PET imaging also are discussed. 

PMID- 25873897
TI  - The histamine H4 receptor: from orphan to the clinic.
AB  - The histamine H4 receptor (H4R) was first noted as a sequence in genomic
      databases that had features of a class A G-protein coupled receptor. This
      putative receptor was found to bind histamine consistent with its homology to
      other histamine receptors and thus became the fourth member of the histamine
      receptor family. Due to the previous success of drugs that target the H1 and H2
      receptors, an effort was made to understand the function of this new receptor and
      determine if it represented a viable drug target. Taking advantage of the vast
      literature on the function of histamine, a search for histamine activity that did
      not appear to be mediated by the other three histamine receptors was undertaken.
      From this asthma and pruritus emerged as areas of particular interest. Histamine
      has long been suspected to play a role in the pathogenesis of asthma, but
      antihistamines that target the H1 and H2 receptors have not been shown to be
      effective for this condition. The use of selective ligands in animal models of
      asthma has now potentially filled this gap by showing a role for the H4R in
      mediating lung function and inflammation. A similar story exists for chronic
      pruritus associated with conditions such as atopic dermatitis. Antihistamines
      that target the H1 receptor are effective in reducing acute pruritus, but are
      ineffective in pruritus experienced by patients with atopic dermatitis. As for
      asthma, animal models have now suggested a role for the H4R in mediating pruritic
      responses, with antagonists of the H4R reducing pruritus in a number of different
      conditions. The anti-pruritic effect of H4R antagonists has recently been shown
      in human clinical studies, validating the preclinical findings in the animal
      models. A selective H4R antagonist inhibited histamine-induced pruritus in health
      volunteers and reduced pruritus in patients with atopic dermatitis. The history
      to date of the H4R provides an excellent example of the deorphanization of a
      novel receptor and the translation of this into clinical efficacy in humans. 

PMID- 25873899
TI  - A method to control phosphoinositides and to analyze PTEN function in living
      cells using voltage sensitive phosphatases.
AB  - Voltage sensitive phosphatases (VSPs), including engineered voltage sensitive
      PTEN, are excellent tools to rapidly and reversibly alter the phosphoinositide
      (PI) content of the plasma membrane in vivo and study the tumor suppressor PTEN.
      However, widespread adoption of these tools is hampered by the requirement for
      electrophysiological instrumentation to control the activity of VSPs.
      Additionally, monitoring and quantifying the PI changes in living cells requires
      sophisticated microscopy equipment and image analysis. Here we present methods
      that bypass these obstacles. First, we explore technically simple means for
      activation of VSPs via extracellularly applied agents or light. Secondly, we
      characterize methods to monitor PI(4,5)P2 and PI(3,4,5)P3 levels using
      fluorescence microscopy or photometry in conjunction with translocation or FRET
      based PI probes, respectively. We then demonstrate the application of these
      techniques by characterizing the effect of known PTEN mutations on its enzymatic
      activity, analyzing the effect of PTEN inhibitors, and detecting in real time
      rapid inhibition of protein kinase B following depletion of PI(3,4,5)P3. Thus, we
      established an approach that does not only allow for rapidly manipulating and
      monitoring PI(4,5)P2 and PI(3,4,5)P3 levels in a population of cells, but also
      facilitates the study of PTEN mutants and pharmacological targeting in mammalian
      cells. 

PMID- 25873901
TI  - Midgut serine proteases and alternative host plant utilization in Pieris
      brassicae L.
AB  - Pieris brassicae L. is a serious pest of cultivated crucifers in several parts of
      the world. Larvae of P. brassicae also feed prolifically on garden nasturtium
      (Tropaeolum majus L., of the family Tropaeolaceae). Proteolytic digestion was
      studied in larvae feeding on multiple hosts. Fourth instars were collected from
      cauliflower fields before transfer onto detached, aerial tissues of selected host
      plants in the lab. Variable levels of midgut proteases were detected in larvae
      fed on different hosts using protein substrates (casein and recombinant RBCL
      cloned from cauliflower) and diagnostic, synthetic substrates. Qualitative
      changes in midgut trypsin activities and quantitative changes in midgut
      chymotrypsin activities were implicated in physiological adaptation of larvae
      transferred to T. majus. Midgut proteolytic activities were inhibited to
      different extents by serine protease inhibitors, including putative trypsin
      inhibitors isolated from herbivore-attacked and herbivore-free leaves of
      cauliflower (CfTI) and T. majus (TpTI). Transfer of larvae to T. majus
      significantly influenced feeding parameters but not necessarily when transferred
      to different tissues of the same host. Results obtained are relevant for devising
      sustainable pest management strategies, including transgenic approaches using
      genes encoding plant protease inhibitors. 

PMID- 25873900
TI  - The casein kinase 2 inhibitor, CX-4945, as an anti-cancer drug in treatment of
      human hematological malignancies.
AB  - The casein kinase 2 (CK2) protein kinase is a pro-survival kinase and therapeutic
      target in treatment of various human cancers. CK2 overexpression has been
      demonstrated in hematological malignancies, including chronic lymphocytic
      leukemia, chronic myeloid leukemia, acute lymphoblastic leukemia, acute myeloid
      leukemia, and multiple myeloma. CX-4945, also known as Silmitasertib, is an
      orally administered, highly specific, ATP-competitive inhibitor of CK2. CX-4945
      induces cytotoxicity and apoptosis and is currently being evaluated in clinical
      trials for treatment of many cancer types. In the past 2 years, the focus on the
      therapeutic potential of CX-4945 has shifted from solid tumors to hematological
      malignancies. CX-4945 exerts anti-proliferative effects in hematological tumors
      by downregulating CK2 expression and suppressing activation of CK2-mediated
      PI3K/Akt/mTOR signaling pathways. Furthermore, combination of CX-4945 with other
      inhibitors yielded synergistic effects in cell death induction. These new
      findings demonstrate that CK2 overexpression contributes to blood cancer cell
      survival and resistance to chemotherapy. Combinatorial use of CX-4945 is a
      promising therapeutic tool for treatment of hematological malignancies. 

PMID- 25873903
TI  - Teacher enthusiasm: a potential cure of academic cheating.
AB  - In this research we claim that teachers' enthusiasm matters regarding student
      engagement in terms of academic cheating. Previous studies found that perceived
      enthusiasm of teachers is positively related to the intrinsic motivation of the
      students. However, it was less investigated how perceived enthusiasm is related
      to cheating. In the first exploratory questionnaire study (N = 244) we found that
      during the exams of those teachers who are perceived to be enthusiastic students
      tend to cheat less. In the second questionnaire study (N = 266) we took academic
      motivations into consideration and we found that the more teachers seem
      enthusiastic the cheating rate will be lower among university students.
      Aggregated teacher enthusiasm was positively related to intrinsic motivation,
      negatively related to amotivation, and not related to extrinsic motivation.
      Aggregated teacher enthusiasm was directly and negatively linked to cheating and
      it explained more variance in cheating than academic motivations together. These
      results suggest that teachers' perceived enthusiasm can be a yet unexplored
      interpersonal factor which could effectively prevent academic cheating. 

PMID- 25873898
TI  - Large-scale production and protein engineering of G protein-coupled receptors for
      structural studies.
AB  - Structural studies of G protein-coupled receptors (GPCRs) gave insights into
      molecular mechanisms of their action and contributed significantly to molecular
      pharmacology. This is primarily due to technical advances in protein engineering,
      production and crystallization of these important receptor targets. On the other
      hand, NMR spectroscopy of GPCRs, which can provide information about their
      dynamics, still remains challenging due to difficulties in preparation of
      isotopically labeled receptors and their low long-term stabilities. In this
      review, we discuss methods used for expression and purification of GPCRs for
      crystallographic and NMR studies. We also summarize protein engineering methods
      that played a crucial role in obtaining GPCR crystal structures. 

PMID- 25873902
TI  - Mitochondrial BKCa channel.
AB  - Since its discovery in a glioma cell line 15 years ago, mitochondrial BKCa
      channel (mitoBKCa) has been studied in brain cells and cardiomyocytes sharing
      general biophysical properties such as high K(+) conductance (~300 pS), voltage
      dependency and Ca(2+)-sensitivity. Main advances in deciphering the molecular
      composition of mitoBKCa have included establishing that it is encoded by the
      Kcnma1 gene, that a C-terminal splice insert confers mitoBKCa ability to be
      targeted to cardiac mitochondria, and evidence for its potential coassembly with
      beta subunits. Notoriously, beta1 subunit directly interacts with cytochrome c
      oxidase and mitoBKCa can be modulated by substrates of the respiratory chain.
      mitoBKCa channel has a central role in protecting the heart from ischemia, where
      pharmacological activation of the channel impacts the generation of reactive
      oxygen species and mitochondrial Ca(2+) preventing cell death likely by impeding
      uncontrolled opening of the mitochondrial transition pore. Supporting this view,
      inhibition of mitoBKCa with Iberiotoxin, enhances cytochrome c release from
      glioma mitochondria. Many tantalizing questions remain open. Some of them are:
      how is mitoBKCa coupled to the respiratory chain? Does mitoBKCa play non
      conduction roles in mitochondria physiology? Which are the functional partners of
      mitoBKCa? What are the roles of mitoBKCa in other cell types? Answers to these
      questions are essential to define the impact of mitoBKCa channel in mitochondria
      biology and disease. 

PMID- 25873904
TI  - Good fences make for good neighbors but bad science: a review of what improves
      Bayesian reasoning and why.
AB  - Bayesian reasoning, defined here as the updating of a posterior probability
      following new information, has historically been problematic for humans. Classic
      psychology experiments have tested human Bayesian reasoning through the use of
      word problems and have evaluated each participant's performance against the
      normatively correct answer provided by Bayes' theorem. The standard finding is of
      generally poor performance. Over the past two decades, though, progress has been
      made on how to improve Bayesian reasoning. Most notably, research has
      demonstrated that the use of frequencies in a natural sampling framework-as
      opposed to single-event probabilities-can improve participants' Bayesian
      estimates. Furthermore, pictorial aids and certain individual difference factors
      also can play significant roles in Bayesian reasoning success. The mechanics of
      how to build tasks which show these improvements is not under much debate. The
      explanations for why naturally sampled frequencies and pictures help Bayesian
      reasoning remain hotly contested, however, with many researchers falling into
      ingrained "camps" organized around two dominant theoretical perspectives. The
      present paper evaluates the merits of these theoretical perspectives, including
      the weight of empirical evidence, theoretical coherence, and predictive power. By
      these criteria, the ecological rationality approach is clearly better than the
      heuristics and biases view. Progress in the study of Bayesian reasoning will
      depend on continued research that honestly, vigorously, and consistently engages
      across these different theoretical accounts rather than staying "siloed" within
      one particular perspective. The process of science requires an understanding of
      competing points of view, with the ultimate goal being integration. 

PMID- 25873905
TI  - Being moved as one of the major aesthetic emotional states: A commentary on
      "Being moved: linguistic representation and conceptual structure".

PMID- 25873906
TI  - Reasoning and choice in the Monty Hall Dilemma (MHD): implications for improving
      Bayesian reasoning.
AB  - The Monty Hall Dilemma (MHD) is a two-step decision problem involving
      counterintuitive conditional probabilities. The first choice is made among three
      equally probable options, whereas the second choice takes place after the
      elimination of one of the non-selected options which does not hide the prize.
      Differing from most Bayesian problems, statistical information in the MHD has to
      be inferred, either by learning outcome probabilities or by reasoning from the
      presented sequence of events. This often leads to suboptimal decisions and
      erroneous probability judgments. Specifically, decision makers commonly develop a
      wrong intuition that final probabilities are equally distributed, together with a
      preference for their first choice. Several studies have shown that repeated
      practice enhances sensitivity to the different reward probabilities, but does not
      facilitate correct Bayesian reasoning. However, modest improvements in
      probability judgments have been observed after guided explanations. To explain
      these dissociations, the present review focuses on two types of causes producing
      the observed biases: Emotional-based choice biases and cognitive limitations in
      understanding probabilistic information. Among the latter, we identify a crucial
      cause for the universal difficulty in overcoming the equiprobability illusion:
      Incomplete representation of prior and conditional probabilities. We conclude
      that repeated practice and/or high incentives can be effective for overcoming
      choice biases, but promoting an adequate partitioning of possibilities seems to
      be necessary for overcoming cognitive illusions and improving Bayesian reasoning.

PMID- 25873907
TI  - The stream of experience when watching artistic movies. Dynamic aesthetic effects
      revealed by the Continuous Evaluation Procedure (CEP).
AB  - Research in perception and appreciation is often focused on snapshots, stills of
      experience. Static approaches allow for multidimensional assessment, but are
      unable to catch the crucial dynamics of affective and perceptual processes; for
      instance, aesthetic phenomena such as the "Aesthetic-Aha" (the increase in liking
      after the sudden detection of Gestalt), effects of expectation, or Berlyne's idea
      that "disorientation" with a "promise of success" elicits interest. We conducted
      empirical studies on indeterminate artistic movies depicting the evolution and
      metamorphosis of Gestalt and investigated (i) the effects of sudden perceptual
      insights on liking; that is, "Aesthetic Aha"-effects, (ii) the dynamics of
      interest before moments of insight, and (iii) the dynamics of complexity before
      and after moments of insight. Via the so-called Continuous Evaluation Procedure
      (CEP) enabling analogous evaluation in a continuous way, participants assessed
      the material on two aesthetic dimensions blockwise either in a gallery or a
      laboratory. The material's inherent dynamics were described via assessments of
      liking, interest, determinacy, and surprise along with a computational analysis
      on the variable complexity. We identified moments of insight as peaks in
      determinacy and surprise. Statistically significant changes in liking and
      interest demonstrated that: (i) insights increase liking, (ii) interest already
      increases 1500 ms before such moments of insight, supporting the idea that it is
      evoked by an expectation of understanding, and (iii) insights occur during
      increasing complexity. We propose a preliminary model of dynamics in liking and
      interest with regard to complexity and perceptual insight and discuss
      descriptions of participants' experiences of insight. Our results point to the
      importance of systematic analyses of dynamics in art perception and appreciation.

PMID- 25873908
TI  - Commentary on: "Evidence of weak conscious experiences in the exclusion task".

PMID- 25873909
TI  - Intentional and automatic numerical processing as predictors of mathematical
      abilities in primary school children.
AB  - Previous studies have suggested that numerical processing relates to mathematical
      performance, but it seems that such relationship is more evident for intentional
      than for automatic numerical processing. In the present study we assessed the
      relationship between the two types of numerical processing and specific
      mathematical abilities in a sample of 109 children in grades 1-6. Participants
      were tested in an ample range of mathematical tests and also performed both a
      numerical and a size comparison task. The results showed that numerical
      processing related to mathematical performance only when inhibitory control was
      involved in the comparison tasks. Concretely, we found that intentional numerical
      processing, as indexed by the numerical distance effect in the numerical
      comparison task, was related to mathematical reasoning skills only when the task
      irrelevant dimension (the physical size) was incongruent; whereas automatic
      numerical processing, indexed by the congruency effect in the size comparison
      task, was related to mathematical calculation skills only when digits were
      separated by small distance. The observed double dissociation highlights the
      relevance of both intentional and automatic numerical processing in mathematical
      skills, but when inhibitory control is also involved. 

PMID- 25873910
TI  - Rational pharmacological approaches for cognitive dysfunction and depression in
      Parkinson's disease.
AB  - Parkinson's disease (PD) is not a single entity but rather a heterogeneous
      neurodegenerative disorder. The present study aims to conduct a critical
      systematic review of the literature to describe the main pharmacological
      strategies to treat cognitive dysfunction and major depressive disorder in PD
      patients. We performed a search of articles cited in PubMed from 2004 to 2014
      using the following MeSH terms (Medical subject headings) "Parkinson disease";
      "Delirium," "Dementia," "Amnestic," "Cognitive disorders," and "Parkinson
      disease"; "depression," "major depressive disorder," "drug therapy." We found a
      total of 71 studies related to pharmacological treatment in cognitive dysfunction
      and 279 studies for pharmacological treatment in major depressive disorder. After
      fulfillment of all the inclusion and exclusion criteria, 13 articles remained for
      cognitive dysfunction and 11 for major depressive disorder, which are presented
      and discussed in this study. Further research into non-motor symptoms of PD may
      provide insights into mechanisms of neurodegeneration, and provide better quality
      of life by using rational drugs. 

PMID- 25873911
TI  - Analysis of microbial communities in the oil reservoir subjected to CO2-flooding
      by using functional genes as molecular biomarkers for microbial CO2
      sequestration.
AB  - Sequestration of CO2 in oil reservoirs is considered to be one of the feasible
      options for mitigating atmospheric CO2 building up and also for the in situ
      potential bioconversion of stored CO2 to methane. However, the information on
      these functional microbial communities and the impact of CO2 storage on them is
      hardly available. In this paper a comprehensive molecular survey was performed on
      microbial communities in production water samples from oil reservoirs experienced
      CO2-flooding by analysis of functional genes involved in the process, including
      cbbM, cbbL, fthfs, [FeFe]-hydrogenase, and mcrA. As a comparison, these
      functional genes in the production water samples from oil reservoir only
      experienced water-flooding in areas of the same oil bearing bed were also
      analyzed. It showed that these functional genes were all of rich diversity in
      these samples, and the functional microbial communities and their diversity were
      strongly affected by a long-term exposure to injected CO2. More interestingly,
      microorganisms affiliated with members of the genera Methanothemobacter,
      Acetobacterium, and Halothiobacillus as well as hydrogen producers in CO2
      injected area either increased or remained unchanged in relative abundance
      compared to that in water-flooded area, which implied that these microorganisms
      could adapt to CO2 injection and, if so, demonstrated the potential for microbial
      fixation and conversion of CO2 into methane in subsurface oil reservoirs. 

PMID- 25873912
TI  - Friends or foes: can we make a distinction between beneficial and harmful strains
      of the Stenotrophomonas maltophilia complex?
AB  - Stenotrophomonas maltophilia is an emerging multi-drug-resistant global
      opportunistic pathogen of environmental, mainly plant-associated origin. It is
      also used as a biocontrol or stress protecting agent for crops in sustainable
      agricultural as well as in bioremediation strategies. In order to establish
      effective protocols to distinguish harmless from harmful strains, our discussion
      must take into consideration the current data available surrounding the ecology,
      evolution and pathogenicity of the species complex. The mutation rate was
      identified as one of several possible criteria for strain plasticity, but it is
      currently impossible to distinguish beneficial from harmful S. maltophilia
      strains. This may compromise the possibility of the release and application for
      environmental biotechnology of this bacterial species. The close relative S.
      rhizophila, which can be clearly differentiated from S. maltophilia, provides a
      harmless alternative for biotechnological applications without human health
      risks. This is mainly because it is unable to growth at the human body
      temperature, 37(?)C due to the absence of heat shock genes and a potentially
      temperature-regulated suicide mechanism. 

PMID- 25873914
TI  - Fluorescence in situ hybridization and sequential catalyzed reporter deposition
      (2C-FISH) for the flow cytometric sorting of freshwater ultramicrobacteria.
AB  - Flow cytometric sorting is a powerful tool to physically separate cells within
      mixed microbial communities. If combined with phylogenetic staining (fluorescence
      in situ hybridization, FISH) it allows to specifically sort defined genotypic
      microbial populations from complex natural samples. However, the targeted
      enrichment of freshwater ultramicrobacteria, such as members of the LD12 clade of
      Alphaproteobacteria (SAR11-IIIb), is still challenging. Current FISH protocols,
      even in combination with signal amplification by catalyzed reporter deposition
      (CARD), are not sufficiently sensitive for the distinction of these bacteria from
      background noise by flow cytometry, presumably due to their low ribosome content
      and small cell sizes. We, therefore, modified a CARD based flow sorting protocol
      with the aim of increasing its sensitivity to a level sufficient for
      ultramicrobacteria. This was achieved by a second signal amplification step
      mediated by horseradish peroxidase labeled antibodies targeted to the
      fluorophores that were previously deposited by CARD-FISH staining. The protocol
      was tested on samples from an oligo-mesotrophic lake. Ultramicrobacteria
      affiliated with LD12 Alphaproteobacteria could be successfully sorted to high
      purity by flow cytometry. The ratios of median fluorescence signal to background
      ranged around 20, and hybridization rates determined by flow cytometry were
      comparable to those obtained by fluorescence microscopy. Potential downstream
      applications of our modified cell staining approach range from the analysis of
      microdiversity within 16S rRNA-defined populations to that of functional
      properties, such as the taxon-specific incorporation rates of organic substrates.

PMID- 25873913
TI  - Genomics of microbial plasmids: classification and identification based on
      replication and transfer systems and host taxonomy.
AB  - Plasmids are important "vehicles" for the communication of genetic information
      between bacteria. The exchange of plasmids transmits pathogenically and
      environmentally relevant traits to the host bacteria, promoting their rapid
      evolution and adaptation to various environments. Over the past six decades, a
      large number of plasmids have been identified and isolated from different
      microbes. With the revolution of sequencing technology, more than 4600 complete
      sequences of plasmids found in bacteria, archaea, and eukaryotes have been
      determined. The classification of a wide variety of plasmids is not only
      important to understand their features, host ranges, and microbial evolution but
      is also necessary to effectively use them as genetic tools for microbial
      engineering. This review summarizes the current situation of the classification
      of fully sequenced plasmids based on their host taxonomy and their features of
      replication and conjugative transfer. The majority of the fully sequenced
      plasmids are found in bacteria in the Proteobacteria, Firmicutes, Spirochaetes,
      Actinobacteria, Cyanobacteria and Euryarcheota phyla, and key features of each
      phylum are included. Recent advances in the identification of novel types of
      plasmids and plasmid transfer by culture-independent methods using samples from
      natural environments are also discussed. 

PMID- 25873915
TI  - Phosphoproteome of the cyanobacterium Synechocystis sp. PCC 6803 and its dynamics
      during nitrogen starvation.
AB  - Cyanobacteria have shaped the earth's biosphere as the first oxygenic
      photoautotrophs and still play an important role in many ecosystems. The ability
      to adapt to changing environmental conditions is an essential characteristic in
      order to ensure survival. To this end, numerous studies have shown that bacteria
      use protein post-translational modifications such as Ser/Thr/Tyr phosphorylation
      in cell signaling, adaptation, and regulation. Nevertheless, our knowledge of
      cyanobacterial phosphoproteomes and their dynamic response to environmental
      stimuli is relatively limited. In this study, we applied gel-free methods and
      high accuracy mass spectrometry toward the detection of Ser/Thr/Tyr
      phosphorylation events in the model cyanobacterium Synechocystis sp. PCC 6803. We
      could identify over 300 phosphorylation events in cultures grown on nitrate as
      exclusive nitrogen source. Chemical dimethylation labeling was applied to
      investigate proteome and phosphoproteome dynamics during nitrogen starvation. Our
      dataset describes the most comprehensive (phospho)proteome of Synechocystis to
      date, identifying 2382 proteins and 183 phosphorylation events and quantifying
      2111 proteins and 148 phosphorylation events during nitrogen starvation. Global
      protein phosphorylation levels were increased in response to nitrogen depletion
      after 24 h. Among the proteins with increased phosphorylation, the PII signaling
      protein showed the highest fold-change, serving as positive control. Other
      proteins with increased phosphorylation levels comprised functions in
      photosynthesis and in carbon and nitrogen metabolism. This study reveals dynamics
      of Synechocystis phosphoproteome in response to environmental stimuli and
      suggests an important role of protein Ser/Thr/Tyr phosphorylation in fundamental
      mechanisms of homeostatic control in cyanobacteria. 

PMID- 25873916
TI  - Isolating the effects of storm events on arctic aquatic bacteria: temperature,
      nutrients, and community composition as controls on bacterial productivity.
AB  - Storm events can pulse nutrients and carbon from soils and provide an important
      subsidy to food webs in oligotrophic streams and lakes. Bacterial nutrient
      limitation and the potential response of stream aquatic bacteria to storm events
      was investigated in arctic tundra environments by manipulating both water
      temperature and inorganic nutrient concentrations in short (up to 4 days) and
      long duration (up to 2 weeks) laboratory mesocosm experiments. Inorganic N and P
      additions increased bacterial production ((14)C-labeled leucine uptake) up to
      seven times over controls, and warmer incubation temperatures increased the speed
      of this response to added nutrients. Bacterial cell numbers also increased in
      response to temperature and nutrient additions with cell-specific carbon uptake
      initially increasing and then declining after 2 days. Bacterial community
      composition (BCC; determined by means of 16S denaturing gradient gel
      electrophoresis fingerprinting) shifted rapidly in response to changes in
      incubation temperature and the addition of nutrients, within 2 days in some
      cases. While the bacteria in these habitats responded to nutrient additions with
      rapid changes in productivity and community composition, water temperature
      controlled the speed of the metabolic response and affected the resultant change
      in bacterial community structure, constraining the potential responses to pulsed
      nutrient subsidies associated with storm events. In all cases, at higher nutrient
      levels and temperatures the effect of initial BCC on bacterial activity was
      muted, suggesting a consistent, robust interaction of temperature, and nutrients
      controlling activity in these aquatic systems. 

PMID- 25873917
TI  - TLR-4 cooperates with Dectin-1 and mannose receptor to expand Th17 and Tc17 cells
      induced by Paracoccidioides brasiliensis stimulated dendritic cells.
AB  - The concomitant use of diverse pattern recognition receptors (PRRs) by innate
      immune cells can result in synergistic or inhibitory activities that profoundly
      influence anti-microbial immunity. Dectin-1 and the mannose receptor (MR) are C
      type lectin receptors (CLRs) previously reported to cooperate with toll-like
      receptors (TLRs) signaling in the initial inflammatory response and in the
      induction of adaptive Th17 and Tc17 immunity mediated by CD4(+) and CD8(+) T
      cells, respectively. The protective immunity against paracoccidioidomycosis, the
      most prevalent fungal infection of Latin America, was previously shown to be
      influenced by these T cell subsets motivating us to study the contribution of
      TLRs, Dectin-1, and MR to the development of Th17/Tc17 immunity. First, curdlan a
      specific Dectin-1 agonist was used to characterize the influence of this receptor
      in the proliferative response and Th17/Tc17 differentiation of naive lymphocytes
      induced by Paracoccidioides brasiliensis activated dendritic cells (DCs) from
      C57BL/6 mice. Then, wild type (WT), Dectin-1(-/-), TLR-2(-/-), and TLR-4(-/-) DCs
      treated or untreated with anti-Dectin-1 and anti-MR antibodies were used to
      investigate the contribution of these receptors in lymphocyte activation and
      differentiation. We verified that curdlan induces an enhanced lymphocyte
      proliferation and development of IL-17 producing CD4(+) and CD8(+) T cells. In
      addition, treatment of WT, TLR-2(-/-), and TLR-4(-/-) DCs by anti-Dectin-1
      antibodies or antigen presentation by Dectin-1(-/-) DCs led to decreased
      lymphoproliferation and impaired Th17 and Tc17 expansion. These responses were
      also inhibited by anti-MR treatment of DCs, but a synergistic action on Th17/Tc17
      differentiation was mediated by TLR-4 and MR. Taken together, our results
      indicate that diverse TLRs and CLRs are involved in the induction of lymphocyte
      proliferation and Th17/Tc17 differentiation mediated by P. brasiliensis activated
      DCs, but a synergist action was restricted to Dectin-1, TLR-4, and MR. 

PMID- 25873918
TI  - Multidrug resistance found in extended-spectrum beta-lactamase-producing
      Enterobacteriaceae from rural water reservoirs in Guantao, China.
AB  - Extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae have been
      isolated from humans and animals across the world. However, data on prevalence of
      ESBL-producing Enterobacteriaceae from rural water reservoirs is limited. This
      study aimed to isolate and characterize ESBL-producing Enterobacteriaceae in
      rural water reservoirs in Guantao, China. ESBL-producing Enterobacteriaceae were
      found in 5 (16.7%) of 30 sampled rural water reservoirs. Sixty-six individual
      isolates expressing an ESBL phenotype were obtained in the present study. Species
      identification showed that 42 representatives of Escherichia coli, 17 Klebsiella
      pneumoniae, 4 Raoultella planticola, and 3 Enterobacter cloacae. Twenty isolates
      contained a single bla gene, including CTX-M (17 strains), TEM (2 strains), and
      SHV (1 strain). Forty-six isolates contained more than one type of beta-lactamase
      genes. ESBL-producing Enterobacteriaceae isolated in this study were all
      multidrug resistant. These findings indicated that the serious contamination of
      ESBL-producing Enterobacteriaceae in rural water reservoirs existed in Guantao,
      China. 

PMID- 25873919
TI  - An Emerging Role for SNARE Proteins in Dendritic Cell Function.
AB  - Dendritic cells (DCs) provide an essential link between innate and adaptive
      immunity. At the site of infection, antigens recognized by DCs via pattern
      recognition receptors, such as Toll-like receptors (TLRs), initiate a specific
      immune response. Depending on the nature of the antigen, DCs secrete distinct
      cytokines with which they orchestrate homeostasis and pathogen clearance.
      Dysregulation of this process can lead to unnecessary inflammation, which can
      result in a plethora of inflammatory diseases. Therefore, the secretion of
      cytokines from DCs is tightly regulated and this regulation is facilitated by
      highly conserved trafficking protein families. These proteins control the
      transport of vesicles from the Golgi complex to the cell surface and between
      organelles. In this review, we will discuss the role of soluble n-ethylmaleimide
      sensitive factor attachment protein receptor proteins (SNAREs) in DCs, both as
      facilitators of secretion and as useful tools to determine the pathways of
      secretion through their definite locations within the cells and inherent
      specificity in opposing binding partners on vesicles and target membranes. The
      role of SNAREs in DC function may present an opportunity to explore these
      proteins as novel targets in inflammatory disease. 

PMID- 25873921
TI  - Identification of Rubisco rbcL and rbcS in Camellia oleifera and their potential
      as molecular markers for selection of high tea oil cultivars.
AB  - Tea oil derived from seeds of Camellia oleifera Abel. is high-quality edible oil
      in China. This study isolated full-length cDNAs of Rubisco subunits rbcL and rbcS
      from C. oleifera. The rbcL has 1,522 bp with a 1,425 bp coding region, encoding
      475 amino acids; and the rbcS has 615 bp containing a 528 bp coding region,
      encoding 176 amino acids. The expression level of the two genes, designated as Co
      rbcL and Co-rbcS, was determined in three C. oleifera cultivars: Hengchong 89,
      Xianglin 1, and Xianglin 14 whose annual oil yields were 546.9, 591.4, and 657.7
      kg ha(-1), respectively. The Co-rbcL expression in 'Xianglin 14' was
      significantly higher than 'Xianglin 1', and 'Xianglin 1' was greater than
      'Hengchong 89'. The expression levels of Co-rbcS in 'Xianglin 1' and 'Xianglin
      14' were similar but were significantly greater than in 'Hengchong 89'. The net
      photosynthetic rate of 'Xianglin 14' was significantly higher than 'Xianglin 1',
      and 'Xianglin 1' was higher than 'Hengchong 89'. Pearson's correlation analysis
      showed that seed yields and oil yields were highly correlated with the expression
      level of Co-rbcL at P < 0.001 level; and the expression of Co-rbcS was correlated
      with oil yield at P < 0.01 level. Net photosynthetic rate was also correlated
      with oil yields and seed yields at P < 0.001 and P < 0.01 levels, respectively.
      Our results suggest that Co-rbcS and Co-rbcL in particular could potentially be
      molecular markers for early selection of high oil yield cultivars. In combination
      with the measurement of net photosynthetic rates, the early identification of
      potential high oil production cultivars would significantly shorten plant
      breeding time and increase breeding efficiency. 

PMID- 25873920
TI  - Employing genome-wide SNP discovery and genotyping strategy to extrapolate the
      natural allelic diversity and domestication patterns in chickpea.
AB  - The genome-wide discovery and high-throughput genotyping of SNPs in chickpea
      natural germplasm lines is indispensable to extrapolate their natural allelic
      diversity, domestication, and linkage disequilibrium (LD) patterns leading to the
      genetic enhancement of this vital legume crop. We discovered 44,844 high-quality
      SNPs by sequencing of 93 diverse cultivated desi, kabuli, and wild chickpea
      accessions using reference genome- and de novo-based GBS (genotyping-by
      sequencing) assays that were physically mapped across eight chromosomes of desi
      and kabuli. Of these, 22,542 SNPs were structurally annotated in different coding
      and non-coding sequence components of genes. Genes with 3296 non-synonymous and
      269 regulatory SNPs could functionally differentiate accessions based on their
      contrasting agronomic traits. A high experimental validation success rate (92%)
      and reproducibility (100%) along with strong sensitivity (93-96%) and specificity
      (99%) of GBS-based SNPs was observed. This infers the robustness of GBS as a high
      throughput assay for rapid large-scale mining and genotyping of genome-wide SNPs
      in chickpea with sub-optimal use of resources. With 23,798 genome-wide SNPs, a
      relatively high intra-specific polymorphic potential (49.5%) and broader
      molecular diversity (13-89%)/functional allelic diversity (18-77%) was apparent
      among 93 chickpea accessions, suggesting their tremendous applicability in rapid
      selection of desirable diverse accessions/inter-specific hybrids in chickpea
      crossbred varietal improvement program. The genome-wide SNPs revealed complex
      admixed domestication pattern, extensive LD estimates (0.54-0.68) and extended LD
      decay (400-500 kb) in a structured population inclusive of 93 accessions. These
      findings reflect the utility of our identified SNPs for subsequent genome-wide
      association study (GWAS) and selective sweep-based domestication trait dissection
      analysis to identify potential genomic loci (gene-associated targets)
      specifically regulating important complex quantitative agronomic traits in
      chickpea. The numerous informative genome-wide SNPs, natural allelic diversity
      led domestication pattern, and LD-based information generated in our study have
      got multidimensional applicability with respect to chickpea genomics-assisted
      breeding. 

PMID- 25873922
TI  - Patterns in hydraulic architecture from roots to branches in six tropical tree
      species from cacao agroforestry and their relation to wood density and stem
      growth.
AB  - For decades it has been assumed that the largest vessels are generally found in
      roots and that vessel size and corresponding sapwood area-specific hydraulic
      conductivity are acropetally decreasing toward the distal twigs. However, recent
      studies from the perhumid tropics revealed a hump-shaped vessel size
      distribution. Worldwide tropical perhumid forests are extensively replaced by
      agroforestry systems often using introduced species of various biogeographical
      and climatic origins. Nonetheless, it is unknown so far what kind of hydraulic
      architectural patterns are developed in those agroforestry tree species and which
      impact this exerts regarding important tree functional traits, such as stem
      growth, hydraulic efficiency and wood density (WD). We investigated wood
      anatomical and hydraulic properties of the root, stem and branch wood in
      Theobroma cacao and five common shade tree species in agroforestry systems on
      Sulawesi (Indonesia); three of these were strictly perhumid tree species, and the
      other three tree species are tolerating seasonal drought. The overall goal of our
      study was to relate these properties to stem growth and other tree functional
      traits such as foliar nitrogen content and sapwood to leaf area ratio. Our
      results confirmed a hump-shaped vessel size distribution in nearly all species.
      Drought-adapted species showed divergent patterns of hydraulic conductivity,
      vessel density, and relative vessel lumen area between root, stem and branch wood
      compared to wet forest species. Confirming findings from natural old-growth
      forests in the same region, WD showed no relationship to specific conductivity.
      Overall, aboveground growth performance was better predicted by specific
      hydraulic conductivity than by foliar traits and WD. Our study results suggest
      that future research on conceptual trade-offs of tree hydraulic architecture
      should consider biogeographical patterns underlining the importance of anatomical
      adaptation mechanisms to environment. 

PMID- 25873924
TI  - Transcriptome-based gene profiling provides novel insights into the
      characteristics of radish root response to Cr stress with next-generation
      sequencing.
AB  - Radish (Raphanus sativus L.) is an important worldwide root vegetable crop with
      high nutrient values and is adversely affected by non-essential heavy metals
      including chromium (Cr). Little is known about the molecular mechanism underlying
      Cr stress response in radish. In this study, RNA-Seq technique was employed to
      identify differentially expressed genes (DEGs) under Cr stress. Based on de novo
      transcriptome assembly, there were 30,676 unigenes representing 60,881
      transcripts isolated from radish root under Cr stress. Differential gene analysis
      revealed that 2985 uingenes were significantly differentially expressed between
      Cr-free (CK) and Cr-treated (Cr600) libraries, among which 1424 were up-regulated
      and 1561 down-regulated. Gene ontology (GO) analysis revealed that these DEGs
      were mainly involved in primary metabolic process, response to abiotic stimulus,
      cellular metabolic process and small molecule metabolic process. Kyoto
      encyclopedia of genes and genomes (KEGG) enrichment analysis showed that the DEGs
      were mainly involved in protein processing in endoplasmic reticulum, starch and
      sucrose metabolism, amino acid metabolism, glutathione metabolism, drug and
      xenobiotics by cytochrome P450 metabolism. RT-qPCR analysis showed that the
      expression patterns of 12 randomly selected DEGs were highly accordant with the
      results from RNA-seq. Furthermore, many candidate genes including signaling
      protein kinases, transcription factors and metal transporters, chelate compound
      biosynthesis and antioxidant system, were involved in defense and detoxification
      mechanisms of Cr stress response regulatory networks. These results would provide
      novel insight into molecular mechanism underlying plant responsiveness to Cr
      stress and facilitate further genetic manipulation on Cr uptake and accumulation
      in radish. 

PMID- 25873925
TI  - How plants manage food reserves at night: quantitative models and open questions.
AB  - In order to cope with night-time darkness, plants during the day allocate part of
      their photosynthate for storage, often as starch. This stored reserve is then
      degraded at night to sustain metabolism and growth. However, night-time starch
      degradation must be tightly controlled, as over-rapid turnover results in
      premature depletion of starch before dawn, leading to starvation. Recent
      experiments in Arabidopsis have shown that starch degradation proceeds at a
      constant rate during the night and is set such that starch reserves are exhausted
      almost precisely at dawn. Intriguingly, this pattern is robust with the
      degradation rate being adjusted to compensate for unexpected changes in the time
      of darkness onset. While a fundamental role for the circadian clock is well
      established, the underlying mechanisms controlling starch degradation remain
      poorly characterized. Here, we discuss recent quantitative models that have been
      proposed to explain how plants can compute the appropriate starch degradation
      rate, a process that requires an effective arithmetic division calculation. We
      review experimental confirmation of the models, and describe aspects that require
      further investigation. Overall, the process of night-time starch degradation
      necessitates a fundamental metabolic role for the circadian clock and, more
      generally, highlights how cells process information in order to optimally manage
      their resources. 

PMID- 25873926
TI  - In vitro shoot proliferation and in vitro and ex vitro root formation of Pyrus
      elaeagrifolia Pallas.
AB  - Shoot-tip cultures of Pyrus elaeagrifolia Pallas, an important gene source for
      drought and chlorosis resistance in pear rootstock breeding, were established
      from a wild mature tree originated from seed. Murashige and Skoog basal medium
      supplemented with different concentrations of benzyladenine (BA) singly or in
      combination with auxin was used in the study. In the initial culture, the highest
      percentages (>80%) of shoot proliferation were obtained in the mediums
      supplemented with 9.0 MUM BA and 0.5 MUM indole-3-acetic acid. In the
      subcultures, the highest shoot proliferation rates were obtained in the medium
      containing 4.5 and 9.0 MUM BA. The shoot proliferation rates ranged from 91.1 +/-
      2.4 to 96.4 +/- 2.0% in the second subculture and from 76.7 +/- 7.8 to 89.4 +/-
      3.3% in the third subculture. In the second subculture, the shoots grown on 9.0
      MUM BA without auxin produced the best proliferation (10.6 +/- 1.6). For the in
      vitro rooting experiments, the highest rooting rate (54.2 +/- 10.4%), root length
      (10.5 +/- 2.4 mm), and root number (2.5 +/- 0.6) were obtained from 10 days dark
      treatment on the medium containing half strength of macronutrients supplemented
      with 5 MUM indole-3-butyric acid (IBA). For the ex vitro rooting experiments,
      shoot rooting was significantly influenced by 10 mM IBA applied as quick-dip
      method. The percentage of rooting was 55 +/- 9.6% and root number was 1.8 +/- 0.3
      at this concentration. 

PMID- 25873923
TI  - Unmasking host and microbial strategies in the Agrobacterium-plant defense tango.
AB  - Coevolutionary forces drive adaptation of both plant-associated microbes and
      their hosts. Eloquently captured in the Red Queen Hypothesis, the complexity of
      each plant-pathogen relationship reflects escalating adversarial strategies, but
      also external biotic and abiotic pressures on both partners. Innate immune
      responses are triggered by highly conserved pathogen-associated molecular
      patterns, or PAMPs, that are harbingers of microbial presence. Upon cell surface
      receptor-mediated recognition of these pathogen-derived molecules, host plants
      mount a variety of physiological responses to limit pathogen survival and/or
      invasion. Successful pathogens often rely on secretion systems to translocate
      host-modulating effectors that subvert plant defenses, thereby increasing
      virulence. Host plants, in turn, have evolved to recognize these effectors,
      activating what has typically been characterized as a pathogen-specific form of
      immunity. Recent data support the notion that PAMP-triggered and effector
      triggered defenses are complementary facets of a convergent, albeit
      differentially regulated, set of immune responses. This review highlights the key
      players in the plant's recognition and signal transduction pathways, with a focus
      on the aspects that may limit Agrobacterium tumefaciens infection and the ways it
      might overcome those defenses. Recent advances in the field include a growing
      appreciation for the contributions of cytoskeletal dynamics and membrane
      trafficking to the regulation of these exquisitely tuned defenses. Pathogen
      counter-defenses frequently manipulate the interwoven hormonal pathways that
      mediate host responses. Emerging systems-level analyses include host
      physiological factors such as circadian cycling. The existing literature
      indicates that varying or even conflicting results from different labs may well
      be attributable to environmental factors including time of day of infection,
      temperature, and/or developmental stage of the host plant. 

PMID- 25873927
TI  - Association of mild kidney dysfunction with silent brain lesions in
      neurologically normal subjects.
AB  - BACKGROUND: Chronic kidney disease (CKD) has been closely associated with stroke.
      Although a large number of studies reported the relationship between CKD and
      different types of asymptomatic brain lesions, few comprehensive analyses have
      been performed for all types of silent brain lesions. METHODS: We performed a
      cross-sectional study involving 1,937 neurologically normal subjects (mean age
      59.4 years). Mild CKD was defined as an estimated glomerular filtration rate
      between 30 and 60 ml/min/1.73 m(2) or positive proteinuria. RESULTS: The
      prevalence of mild CKD was 8.7%. Univariate analysis revealed an association
      between CKD and all silent brain lesions, including silent brain infarction,
      periventricular hyperintensity, subcortical white matter lesion, and microbleeds,
      in addition to hypertension and diabetes mellitus after adjusting for age and
      sex. In binary logistic regression analysis, the presence of CKD was a
      significant risk factor for all types of silent brain lesions, independent of
      other risk factors. CONCLUSIONS: These results suggest that mild CKD is
      independently associated with all types of silent brain lesions, even in
      neurologically normal subjects.

PMID- 25873928
TI  - Association between DNA Methylation of the BDNF Promoter Region and Clinical
      Presentation in Alzheimer's Disease.
AB  - BACKGROUND/AIMS: In the present study, we examined whether DNA methylation of the
      brain-derived neurotrophic factor (BDNF) promoter is associated with the
      manifestation and clinical presentation of Alzheimer's disease (AD). METHODS: Of
      20 patients with AD and 20 age-matched normal controls (NCs), the DNA methylation
      of the BDNF promoter (measured using peripheral blood samples) was completely
      analyzed in 12 patients with AD and 6 NCs. The resulting methylation levels were
      compared statistically. Next, we investigated the correlation between the DNA
      methylation levels and the clinical presentation of AD. RESULTS: The total
      methylation ratio (in %) of the 20 CpG sites was significantly higher in the AD
      patients (5.08 +/- 5.52%) than in the NCs (2.09 +/- 0.81%; p < 0.05). Of the 20
      CpG sites, the methylation level at the CpG4 site was significantly higher in the
      AD subjects than in the NCs (p < 0.05). Moreover, the methylation level was
      significantly and negatively correlated with some neuropsychological test
      subscores (registration, recall, and prehension behavior scores; p < 0.05).
      CONCLUSION: These results suggest that the DNA methylation of the BDNF promoter
      may significantly influence the manifestation of AD and might be associated with
      its neurocognitive presentation.

PMID- 25873929
TI  - A Direct Performance Test for Assessing Activities of Daily Living in Patients
      with Mild Degenerative Dementia: The Development of the ETAM and Preliminary
      Results.
AB  - BACKGROUND: There are currently only a few performance tests that assess the
      capacity to perform activities of daily living. These measures frequently require
      a long time to administer, are strongly cognition oriented, or have not been
      adequately validated. METHODS: The Erlangen Test of Activities of Daily Living in
      Mild Dementia (ETAM) was developed in a 4-phase process that was based on the
      International Classification of Functioning, Disability, and Health (ICF). A
      pilot study was conducted on 30 subjects with mild dementia with a mean age of 80
      years. The subjects' mean score on the MMSE was 21.5. Twenty-one of the 30
      subjects were women. RESULTS: Ten items were developed and tested in the pilot
      study. The mean time required to complete the test was 26 min. The item analysis
      showed difficulties that ranged primarily from r = 0.28 to r = 0.79. The ETAM had
      a moderate correlation with the MMSE (rMMSE = 0.310) and a low correlation with
      the Geriatric Depression Scale-15 (GDS-15; rGDS-15 = 0.149). CONCLUSION: The
      preliminary version of the ETAM is quick and easy to use and has predominantly
      satisfactory item characteristics. There still is the need to revise the items
      'giving directions' and 'making tea' with regard to standardisation.

PMID- 25873930
TI  - Use of the MoCA in Detecting Early Alzheimer's Disease in a Spanish-Speaking
      Population with Varied Levels of Education.
AB  - BACKGROUND/AIMS: Performance on the Montreal Cognitive Assessment (MoCA) has been
      demonstrated to be dependent on the educational level. The purpose of this study
      was to identify how to best adjust MoCA scores and to identify MoCA items most
      sensitive to cognitive decline in incipient Alzheimer's disease (AD) in a Spanish
      speaking population with varied levels of education. METHODS: We analyzed data
      from 50 Spanish-speaking participants. We examined the pattern of diagnosis
      adjusted MoCA residuals in relation to education and compared four alternative
      score adjustments using bootstrap sampling. Sensitivity and specificity analyses
      were performed for the raw and each adjusted score. The interval reliability of
      the MoCA as well as item discrimination and item validity were examined. RESULTS:
      We found that with progressive compensation added for those with lower education,
      unexplained residuals decreased and education-residual association moved to zero,
      suggesting that more compensation was necessary to better adjust MoCA scores in
      those with a lower educational level. Cube copying, sentence repetition, delayed
      recall, and orientation were most sensitive to cognitive impairment due to AD.
      CONCLUSION: A compensation of 3-4 points was needed for <6 years of education.
      Overall, the Spanish version of the MoCA maintained adequate psychometric
      properties in this population.

PMID- 25873931
TI  - Effectiveness and Safety of MLC601 in the Treatment of Mild to Moderate
      Alzheimer's Disease: A Multicenter, Randomized Controlled Trial.
AB  - BACKGROUND: MLC601 is a possible modulator of amyloid precursor protein
      processing, and in a clinical trial study MLC601 showed some effectiveness in
      cognitive function in Alzheimer's disease (AD) patients. We aimed to evaluate the
      effectiveness and safety of MLC601 in the treatment of mild to moderate AD as
      compared to 3 approved cholinesterase inhibitors (ChEIs) including donepezil,
      rivastigmine and galantamine. METHODS: In a multicenter, nonblinded, randomized
      controlled trial, 264 volunteers with AD were randomly divided into 4 groups of
      66; groups 1, 2, 3 and 4 received donepezil, rivastigmine, MLC601 and
      galantamine, respectively. Subjects underwent a clinical diagnostic interview and
      a cognitive/functional battery including the Mini-Mental State Examination (MMSE)
      and Alzheimer's Disease Assessment Scale - Cognitive subscale (ADAS-Cog).
      Patients were visited every 4 months, and the score of cognition was recorded by
      the neurologists. RESULTS: There were no significant differences in age, sex,
      marital status and baseline score of cognition among the 4 groups. In total, 39
      patients (14.7%) left the study. Trend of cognition changes based on the
      modifications over the time for MMSE and ADAS-cog scores did not differ
      significantly among groups (p = 0.92 for MMSE and p = 0.87 for ADAS-Cog).
      CONCLUSION: MLC601 showed a promising safety profile and also efficacy compared
      to 3 FDA-approved ChEIs.

PMID- 25873932
TI  - Reduced sympathetic response to head-up tilt in subjects with mild cognitive
      impairment or mild Alzheimer's dementia.
AB  - BACKGROUND: Hemodynamic control was compared in patients with mild cognitive
      impairment (MCI) or mild Alzheimer's dementia (AD) as well as in healthy elderly
      subjects. METHODS: Noninvasive, continuous hemodynamic recordings were obtained
      from 14 patients and 48 controls during supine rest (tilt of 30 and 70 degrees ).
      Cardiac output, end-diastolic volume, total peripheral resistance, heart rate
      variability (HRV), systolic blood pressure variability (SBPV), and baroreceptor
      sensitivity were calculated. RESULTS: At 70 degrees  tilt, the HRV indices
      differed significantly, with higher high-frequency (HF) variability as well as
      lower low-frequency (LF) variability and LF/HF ratios in the patients. The
      patients had significantly lower SBPV in the LF range at 30 degrees  tilt.
      CONCLUSIONS: The results indicate a poorer sympathetic response to orthostatic
      stress in MCI and mild AD. (c) 2015 S. Karger AG, Basel.

PMID- 25873933
TI  - A case of fibrillary glomerulonephritis associated with thrombotic
      microangiopathy and anti-glomerular basement membrane antibody.
AB  - We present the first report of a case of fibrillary glomerulonephritis (FGN)
      associated with thrombotic microangiopathy (TMA) and anti-glomerular basement
      membrane antibody (anti-GBM antibody). A 54-year-old man was admitted to our
      hospital for high fever and anuria. On the first hospital day, we initiated
      hemodialysis for renal dysfunction. Laboratory data revealed normocytic
      normochromic anemia with schistocytes in the peripheral smear, thrombocytopenia,
      increased serum lactate dehydrogenase, decreased serum haptoglobin, and negative
      results for both direct and indirect Coombs tests. Based on these results, we
      diagnosed TMA. Assays conducted several days later indicated a disintegrin-like
      and metalloprotease with a thrombospondin motif 13 (ADAMTS13) activity of 31.6%,
      and ADAMTS13 inhibitors were negative. We started plasma exchange using fresh
      frozen plasma and steroid pulse therapy. Anti-GBM antibody was found to be
      positive. Renal biopsy showed FGN. Blood pressure rose on the 46th hospital day,
      and mild convulsions developed. Based on magnetic resonance imaging of the head,
      the patient was diagnosed with reversible posterior leukoencephalopathy syndrome.
      Hypertension persisted despite administration of multiple antihypertensive
      agents, and the patient experienced a sudden generalized seizure. Computed
      tomography of the head showed multiple cerebral hemorrhages. However, his blood
      pressure subsequently decreased and the platelet count increased. TMA remitted
      following 36 plasma exchange sessions, but renal function was not restored, and
      maintenance hemodialysis was continued. The patient was discharged on the 119th
      day of hospitalization. In conclusion, it was shown that TMA, FGN and anti-GBM
      antibody were closely related. 

PMID- 25873934
TI  - Research on potential biomarkers in hereditary hemorrhagic telangiectasia.
AB  - Hereditary hemorrhagic telangiectasia (HHT) is a genetically heterogeneous
      disorder, involving mutations in two predominant genes known as Endoglin (ENG;
      HHT1) and activin receptor-like kinase 1 (ACVRL1/ALK1; HHT2), as well as in some
      less frequent genes, such as MADH4/SMAD4 (JP-HHT) or BMP9/GDF2 (HHT5). The
      diagnosis of HHT patients currently remains at the clinical level, according to
      the "Curacao criteria," whereas the molecular diagnosis is used to confirm or
      rule out suspected HHT cases, especially when a well characterized index case is
      present in the family or in an isolated population. Unfortunately, many suspected
      patients do not present a clear HHT diagnosis or do not show pathogenic mutations
      in HHT genes, prompting the need to investigate additional biomarkers of the
      disease. Here, several HHT biomarkers and novel methodological approaches
      developed during the last years will be reviewed. On one hand, products detected
      in plasma or serum samples: soluble proteins (vascular endothelial growth factor,
      transforming growth factor beta1, soluble endoglin, angiopoietin-2) and microRNA
      variants (miR-27a, miR-205, miR-210). On the other hand, differential HHT gene
      expression fingerprinting, next generation sequencing of a panel of genes
      involved in HHT, and infrared spectroscopy combined with artificial neural
      network patterns will also be reviewed. All these biomarkers might help to
      improve and refine HHT diagnosis by distinguishing from the non-HHT population. 

PMID- 25873935
TI  - Annotation and curation of uncharacterized proteins- challenges.
AB  - Hypothetical proteins (HPs) are the proteins predicted to be expressed from an
      open reading frame, making a substantial fraction of proteomes in both
      prokaryotes and eukaryotes. Genome projects have led to the identification of
      many therapeutic targets, the putative function of the protein, and their
      interactions. In this review we enlist various methods linking annotation to
      structural and functional prediction of HPs that assist in the discovery of new
      structures and functions serving as markers and pharmacological targets for drug
      designing, discovery, and screening. Further we give an overview of how mass
      spectrometry as an analytical technique is used to validate protein
      characterisation. We discuss how microarrays and protein expression profiles help
      understanding the biological systems through a systems-wide study of proteins and
      their interactions with other proteins and non-proteinaceous molecules to control
      complex processes in cells. Finally, we articulate challenges on how next
      generation sequencing methods have accelerated multiple areas of genomics with
      special focus on uncharacterized proteins. 

PMID- 25873937
TI  - Scorpionism in Brazil in the years 2000 to 2012.
AB  - BACKGROUND: Scorpionism is a serious public health problem in Brazil. Nationwide
      epidemiological analyses of scorpion stings are scarce. In this context, the
      present study aims to provide an epidemiological analysis of accidents involving
      scorpions in Brazil. METHODS: An analytical epidemiological study of the scorpion
      accidents reported in the Information System for Notifiable Diseases (SINAN) was
      conducted from 2000 to 2012 in Brazil. RESULTS: During this period, 482,616
      accidents and 728 deaths were reported. The annual average incidence and
      mortality rates per 100,000 inhabitants were 19.6 and 0.030, respectively, with
      annual average lethality rate of 0.16%. The highest accident frequency was
      recorded in male subjects, aged 20-49 years, from September to December and in
      urban areas, except in the northern region of the country, where accidents were
      most frequent in June and July, and in rural areas. Males up to age 9 and rural
      areas were defined as an age group and area for greatest death risk,
      respectively. CONCLUSIONS: Scorpionism in Brazil is a predominantly urban health
      problem that mostly affects people at an economically active age. The Northeast
      and Southeast hold the majority of cases and deaths, as well as the highest
      annual incidence and mortality averages, but the Central West and North presented
      the highest average annual lethality rates. The epidemiological changes described
      in this study highlight the need for intensifying health surveillance actions to
      prevent scorpion accidents in Brazil.

PMID- 25873936
TI  - A re-formulation of generalized linear mixed models to fit family data in genetic
      association studies.
AB  - The generalized linear mixed model (GLMM) is a useful tool for modeling genetic
      correlation among family data in genetic association studies. However, when
      dealing with families of varied sizes and diverse genetic relatedness, the GLMM
      has a special correlation structure which often makes it difficult to be
      specified using standard statistical software. In this study, we propose a
      Cholesky decomposition based re-formulation of the GLMM so that the re-formulated
      GLMM can be specified conveniently via "proc nlmixed" and "proc glimmix" in SAS,
      or OpenBUGS via R package BRugs. Performances of these procedures in fitting the
      re-formulated GLMM are examined through simulation studies. We also apply this re
      formulated GLMM to analyze a real data set from Type 1 Diabetes Genetics
      Consortium (T1DGC). 

PMID- 25873938
TI  - Infiltrated plaques resulting from an injury caused by the common octopus
      (Octopus vulgaris): a case report.
AB  - Several species of octopus are considered venomous due to toxins present in the
      glands connected to their "beak", which may be associated with hunt and kill of
      prey. Herein, we report an accident involving a common octopus (Octopus vulgaris)
      that injured an instructor during a practical biology lesson and provoked an
      inflamed infiltrated plaque on the hand of the victim. The lesion was present for
      about three weeks and was treated with cold compresses and anti-inflammatory
      drugs. It was healed ten days after leaving a hyperchromic macule at the bite
      site. The probable cause of the severe inflammation was the digestive enzymes of
      the glands and not the neurotoxins of the venom. 

PMID- 25873939
TI  - Antileishmanial and antitrypanosomal activity of the cutaneous secretion of
      Siphonops annulatus.
AB  - BACKGROUND: Among the tropical parasitic diseases, those caused by protozoans are
      considered a challenge to public health, being represented by leishmaniasis and
      Chagas disease. In view of the low effectiveness and toxicity of the current
      therapy, animal venoms such as amphibian secretions have been used as a promising
      source of new drug prototypes. The present work aimed to achieve bioguided
      fractionation of metabolites present in a cutaneous secretion of the caecilian
      Siphonops annulatus (Amphibia: Gymnophiona: Siphonopidae) with antileishmanial
      and antitrypanosomal activity. METHODS: Through liquid-liquid partition and
      chromatographic techniques, the secretion was fractionated using bioguided
      assays. The 50% inhibitory concentration (IC50) of the main fraction (SaFr1) was
      studied against Leishmania (L.) infantum promastigotes and intracellular
      amastigotes, trypomastigotes of Trypanosoma cruzi and mammalian cells; viability
      was detected by the colorimetric MTT assay. By using a spectrofluorimetric assay
      with the probe SYTOX(r) Green and transmission electron microscopy (TEM), we also
      investigated the potential damage caused by SaFr1 in the plasma membrane and
      mitochondria of Leishmania. RESULTS: The bioguided assay enabled isolation of a
      highly purified fraction (SaFr1) with an IC50 of 0.065 MUg/mL against
      promastigotes and 2.75 MUg/mL against trypomastigotes. Due to its high toxicity
      to peritoneal macrophages, SaFr1 showed no selectivity towards the intracellular
      forms of Leishmania. Ultrastructural studies with Leishmania demonstrated severe
      mitochondrial damage and the formation of large cytoplasmic vacuoles, leading to
      the parasite's death within a few hours. Nevertheless, it caused no alteration in
      the plasma membrane permeability as detected by the fluorescent probe and TEM.
      CONCLUSIONS: The present study demonstrated for the first time the antiparasitic
      activity of the skin secretion of the caecilian S. annulatus against Leishmania
      and T. cruzi, confirming that skin secretions of these amphibians, similarly to
      those of anurans and salamanders, are also potential tools for the development of
      new drug candidates against neglected diseases.

PMID- 25873940
TI  - Virulence factors and antibiotic resistance of Helicobacter pylori isolated from
      raw milk and unpasteurized dairy products in Iran.
AB  - BACKGROUND: Despite the high importance of Helicobacter pylori, the origin and
      transmission of this bacterium has not been clearly determined. According to
      controversial theories and results of previous studies, animal source foods -
      especially milk - play an important role in the transmission of H. pylori to
      humans. The aim of the present study was to determine the distribution of vacA,
      cagA, iceA and oipA virulence factors in H. pylori strains isolated from milk and
      dairy products and study their antimicrobial resistance properties. METHODS: A
      total of 520 raw milk and 400 traditional dairy product samples were cultured and
      tested. Those that were H. pylori-positive were analyzed for the presence of
      vacA, cagA, iceA and oipA virulence factors. Antimicrobial susceptibility testing
      was performed by the disk diffusion method. RESULTS: One hundred and three out of
      520 milk samples (19.8%) and 77 out of 400 dairy products samples (19.2%) were
      contaminated with H. pylori. The most frequently contaminated samples were ovine
      milk (35%) and traditional cheese (30%). Total prevalence of vacA, cagA, iceA and
      oipA factors were 75%, 76.6%, 41.6% and 25%, respectively. H. pylori strains of
      milk and dairy products harbored high levels of resistance to ampicillin (84.4%),
      tetracycline (76.6%), erythromycin (70.5%) and metronidazole (70%). CONCLUSIONS:
      High presence of antibiotic-resistant strains of H. pylori suggest that milk and
      dairy samples may be the sources of bacteria that can cause severe infection. Our
      findings should raise awareness about antibiotic resistance in H. pylori strains
      in Iran.

PMID- 25873941
TI  - Envenomation caused by Rhopalurus amazonicus Lourenco, 1986 (Scorpiones,
      Buthidae) in Para State, Brazil.
AB  - Scorpions, mainly those belonging to the genus Tityus cause many deaths and
      injuries in Brazil, with tens of thousands of envenomations notified every year.
      However, injuries involving other scorpion species are scarcely registered. Among
      the sixteen species of the genus Rhopalurus, Thorell, 1876, described up to date,
      nine are found in this country, with only a confirmed case of human envenomation
      provoked by R. agamemnon Koch, 1839. The present case reports, for the first
      time, a case of scorpion sting in a human victim involving Rhopalurus amazonicus,
      endemic species of the west region of the Para state, Amazon, Brazil. The
      symptoms of envenomation were local pain and paresthesia. This study contributes
      to develop the knowledge on venomous scorpions, particularly those that may cause
      envenomations in this region.

PMID- 25873942
TI  - Multiple correspondence analysis as a tool for analysis of large health surveys
      in African settings.
AB  - BACKGROUND: More than two thirds of the total population of Ethiopia is estimated
      to be at risk of malaria. Therefore, malaria is the leading public health problem
      in Ethiopia. OBJECTIVE: To investigate the determinants of malaria Rapid
      Diagnosis Test (RDT) result and the association between socio-economic,
      demographic and geographic factors. METHOD: The study used data from household
      cluster malaria survey which was conducted from December 2006 to January 2007. A
      total of 224 clusters of about 25 households each were selected from the Amhara,
      Oromiya and Southern Nation Nationalities and People (SNNP) regions of Ethiopia.
      A multiple correspondence analysis was used to jointly analyse malaria RDT
      result, socio-economic, demographic and geographic factors. RESULTS: The result
      from multiple correspondence analysis shows that there is association between
      malaria RDT result and different socio-economic, demographic and geographic
      variables. CONCLUSION: There is an indication that some socio-economic,
      demographic and geographic factors have joint effects. It is important to confirm
      the association between socio-economic, demographic and geographic factors using
      advanced statistical techniques.

PMID- 25873943
TI  - Classifying dementia using local binary patterns from different regions in
      magnetic resonance images.
AB  - Dementia is an evolving challenge in society, and no disease-modifying treatment
      exists. Diagnosis can be demanding and MR imaging may aid as a noninvasive method
      to increase prediction accuracy. We explored the use of 2D local binary pattern
      (LBP) extracted from FLAIR and T1 MR images of the brain combined with a Random
      Forest classifier in an attempt to discern patients with Alzheimer's disease
      (AD), Lewy body dementia (LBD), and normal controls (NC). Analysis was conducted
      in areas with white matter lesions (WML) and all of white matter (WM). Results
      from 10-fold nested cross validation are reported as mean accuracy, precision,
      and recall with standard deviation in brackets. The best result we achieved was
      in the two-class problem NC versus AD + LBD with total accuracy of 0.98 (0.04).
      In the three-class problem AD versus LBD versus NC and the two-class problem AD
      versus LBD, we achieved 0.87 (0.08) and 0.74 (0.16), respectively. The
      performance using 3DT1 images was notably better than when using FLAIR images.
      The results from the WM region gave similar results as in the WML region. Our
      study demonstrates that LBP texture analysis in brain MR images can be
      successfully used for computer based dementia diagnosis. 

PMID- 25873944
TI  - Clustering molecular dynamics trajectories for optimizing docking experiments.
AB  - Molecular dynamics simulations of protein receptors have become an attractive
      tool for rational drug discovery. However, the high computational cost of
      employing molecular dynamics trajectories in virtual screening of large
      repositories threats the feasibility of this task. Computational intelligence
      techniques have been applied in this context, with the ultimate goal of reducing
      the overall computational cost so the task can become feasible. Particularly,
      clustering algorithms have been widely used as a means to reduce the
      dimensionality of molecular dynamics trajectories. In this paper, we develop a
      novel methodology for clustering entire trajectories using structural features
      from the substrate-binding cavity of the receptor in order to optimize docking
      experiments on a cloud-based environment. The resulting partition was selected
      based on three clustering validity criteria, and it was further validated by
      analyzing the interactions between 20 ligands and a fully flexible receptor (FFR)
      model containing a 20 ns molecular dynamics simulation trajectory. Our proposed
      methodology shows that taking into account features of the substrate-binding
      cavity as input for the k-means algorithm is a promising technique for accurately
      selecting ensembles of representative structures tailored to a specific ligand. 

PMID- 25873945
TI  - Comparison of a 4-Day versus 2-Day Low Fiber Diet Regimen in Barium Tagging CT
      Colonography in Incomplete Colonoscopy Patients.
AB  - Our aim was to compare the amount of residual feces, residual fluid, the tagging
      quality, and patient compliance using 4-day versus 2-day low fiber diet regimen
      in barium tagging CT colonography in incomplete colonoscopy patients. Methods. A
      total of 101 patients who underwent CT colonography were assigned to 2-day diet
      group (n = 56) and 4-day diet group (n = 45). Fecal tagging was achieved with
      barium sulphate while bisacodyl and sennoside B were used for bowel preparation.
      Residual solid stool was divided into two groups measuring <6 mm and >=6 mm. We
      graded the residual fluid, tagging quality for solid stool, and fluid per bowel
      segment. We performed a questionnaire to assess patient compliance. Results. 604
      bowel segments were evaluated. There was no significant difference between 2-day
      and 4-day diet groups with respect to residual solid stool, residual fluid,
      tagging quality for stool, and fluid observed in fecal tag CT colonography (P >
      0.05). The prevalence of moderate discomfort was significantly higher in 4-day
      group (P < 0.001). Conclusion. Our study shows that 2-day limited bowel
      preparation regimen for fecal tag CT colonography is a safe and reasonable
      technique to evaluate the entire colon, particularly in incomplete conventional
      colonoscopy patients. 

PMID- 25873946
TI  - Urinary angiopoietin-2 is associated with albuminuria in patients with type 2
      diabetes mellitus.
AB  - Aims. To evaluate the levels of angiopoietin-1 (Ang-1), Ang-2, and vascular
      endothelial growth factor (VEGF) in serum and urine, and their association with
      albuminuria in patients with type 2 diabetes mellitus. Methods. In 113 type 2
      diabetic patients with normoalbuminuria, microalbuminuria, and macroalbuminuria
      and 30 healthy controls, the levels of Ang-1, Ang-2, and VEGF in serum and urine
      were measured by enzyme-linked immunosorbent assay (ELISA). Results. Urinary and
      serum levels of Ang-2 were significantly higher in diabetic patients with
      normoalbuminuria than in healthy controls. Increased urinary Ang-2 level was
      positively associated with the degree of albuminuria. Urinary Ang-1 levels were
      significantly higher in normoalbuminuria patients and lower in macroalbuminuria
      patients than in controls. The levels of urinary VEGF increased in the
      albuminuria subgroup, though serum levels of Ang-1 and VEGF did not change.
      Urinary Ang-2 levels were correlated positively with albuminuria and negatively
      with glomerular filtration rate (GFR). Stepwise multiple regression analysis
      identified albuminuria (P < 0.001) and GFR (P = 0.001) as significant predictors
      of urinary Ang-2. Conclusions. Our data suggest that urinary Ang-2 is stepwise
      increased with renal damage in patients with type 2 diabetes mellitus and is
      associated with albuminuria. 

PMID- 25873947
TI  - The endocrine role of estrogens on human male skeleton.
AB  - Before the characterization of human and animal models of estrogen deficiency,
      estrogen action was confined in the context of the female bone. These interesting
      models uncovered a wide spectrum of unexpected estrogen actions on bone in males,
      allowing the formulation of an estrogen-centric theory useful to explain how sex
      steroids act on bone in men. Most of the principal physiological events that take
      place in the developing and mature male bone are now considered to be under the
      control of estrogen. Estrogen determines the acceleration of bone elongation at
      puberty, epiphyseal closure, harmonic skeletal proportions, the achievement of
      peak bone mass, and the maintenance of bone mass. Furthermore, it seems to
      crosstalk with androgen even in the determination of bone size, a more androgen
      dependent phenomenon. At puberty, epiphyseal closure and growth arrest occur when
      a critical number of estrogens is reached. The same mechanism based on a critical
      threshold of serum estradiol seems to operate in men during adulthood for bone
      mass maintenance via the modulation of bone formation and resorption in men. This
      threshold should be better identified in-between the ranges of 15 and 25 pg/mL.
      Future basic and clinical research will optimize strategies for the management of
      bone diseases related to estrogen deficiency in men. 

PMID- 25873948
TI  - Pituitary disorders and osteoporosis.
AB  - Various hormonal disorders can influence bone metabolism and cause secondary
      osteoporosis. The consequence of this is a significant increase of fracture risk.
      Among pituitary disorders such effects are observed in patients with Cushing's
      disease, hyperprolactinemia, acromegaly, and hypopituitarism. Severe osteoporosis
      is the result of the coexistence of some of these disorders and hypogonadism at
      the same time, which is quite often. 

PMID- 25873949
TI  - Liver Injury Indicating Fatty Liver but Not Serologic NASH Marker Improves under
      Metformin Treatment in Polycystic Ovary Syndrome.
AB  - Objective. Polycystic ovary syndrome (PCOS) is associated with obesity and
      insulin resistance (IR), key features of nonalcoholic steatohepatitis (NASH).
      Cytokeratin 18 fragments (M30) have been established as a serum marker for NASH.
      The insulin sensitizer metformin improves hepatic IR. This study evaluates the
      influence of MF on serologic NASH (sNASH) in patients with PCOS. Patients and
      Methods. In 89 patients, metabolic parameters, liver injury indicating fatty
      liver (LIFL), and M30 were assessed at baseline and after metformin treatment.
      Patients with initial IR were subdivided into dissolved (PCOS-exIR) and
      persistent IR (PCOS-PIR) after treatment and compared to an initially insulin
      sensitive PCOS group (PCOS-C). Results. Improvement of LIFL prevalence could be
      seen in PCOS-C and PCOS-exIR compared to PCOS-PIR (-19.4, resp., -12.0% versus
      7.2%, Chi(2) = 29.5, P < 0.001) without change in sNASH prevalence. In PCOS-PIR,
      ALT levels increased significantly accompanied by a nominal, nonsignificant M30
      increase. Conclusions. Metformin improves LIFL in subgroups of patients with PCOS
      without influencing sNASH. This could either indicate a missing effect of
      metformin on NAFLD or slowed disease progression. Further studies are needed to
      elucidate NAFLD in the context of PCOS and potential therapeutic options. 

PMID- 25873950
TI  - Iodine Supplementation: Usage "with a Grain of Salt".
AB  - Iodine supplementation through salt iodization is a worldwide, effective strategy
      for preventing iodine deficiency-related problems. Its safety and efficacy
      profile has been extensively investigated, and benefits far outweigh the
      potential iodine-induced risks. Moreover, iodine supplementation during pregnancy
      in order to avoid brain damage in the newborn is considered a mainstay of
      preventive medicine. Exposure to high amounts of iodine is actually well
      tolerated in most cases and can be unrecognized. Nevertheless, at-risk
      individuals may develop thyroid dysfunction even when they are exposed to
      increases in iodine intake universally considered as safe. Iodine-induced thyroid
      disorders include thyroid autoimmunity, thyrotoxicosis, iodine-induced goiter,
      and hypothyroidism. Moreover, a relationship between iodine intake and histotype
      distribution of differentiated thyroid cancer has been observed, with a
      progressive shift from follicular to papillary thyroid cancer. To date,
      evaluating iodine status in a clinical setting has limitations, and assessing the
      actual risk for each individual can be challenging, since it is influenced by
      personal history, genetics, and environmental factors. In conclusion, iodine
      supplementation programs need to be continued and strengthened, but iodine should
      be used "with a grain of salt," because a growing number of susceptible
      individuals will be exposed to the risk of developing iodine-induced thyroid
      disorders. 

PMID- 25873951
TI  - Hidden metabolic disturbances in women with normal glucose tolerance five years
      after gestational diabetes.
AB  - Background. The study aimed to assess whether women with prior gestational
      diabetes (pGDM), despite maintenance of normal glucose tolerance (NGT) five years
      after delivery, display metabolic disturbances compared to healthy controls.
      Methods. 45 pGDM with NGT were compared to 18 women without a history of GDM
      (CON), matched for age (37.0 +/- 4.1 versus 35.2 +/- 5.3, P = ns) and BMI (24.3
      +/- 3.1 versus 23.3 +/- 3.3, P = ns). Metabolic parameters were derived from oral
      and intravenous glucose tolerance tests; furthermore lipid profile, C-reactive
      protein (CRP), adiponectin, leptin, and glucagon were assessed. Results. Five
      years postpartum, pGDM had increased glucose concentrations during the OGTT (AUC:
      1.12 +/- 0.15 versus 1.0 +/- 0.12 mol/L * min, P = 0.003) and insulin sensitivity
      was decreased compared to CON (OGIS: 467.2 +/- 64.1 versus 510.6 +/- 53.1 mL/min
      * m(2), P = 0.01). pGDM had lower adiponectin (8.1 +/- 2.6 versus 12.6 +/- 5.3, P
      < 0.008) but increased waist circumference and CRP compared to CON. Conclusions.
      Despite diagnosis of normal glucose tolerance, pGDM are characterized by
      hyperglycemia and insulin resistance compared to healthy controls, accompanied by
      decreased adiponectin and increased CRP concentrations, thus linking metabolic
      disturbances to an increased cardiovascular risk in pGDM. 

PMID- 25873952
TI  - A Single 60 mg Dose of Denosumab Might Improve Hepatic Insulin Sensitivity in
      Postmenopausal Nondiabetic Severe Osteoporotic Women.
AB  - Background. The RANKL/RANK/OPG signaling pathway is crucial for the regulation of
      osteoclast activity and bone resorption being activated in osteoporosis. The
      pathway has been also suggested to influence glucose metabolism as observed in
      chronic low inflammation. Aim. To test whether systemic blockage of RANKL by the
      monoclonal antibody denosumab influences glucose metabolism in osteoporotic
      women. Study Design. This is a prospective study on the effect of a
      subcutaneously injected single 60 mg dose of denosumab in 14 postmenopausal
      severe osteoporotic nondiabetic women evaluated at baseline and 4 and 12 weeks
      after their first injection by an oral glucose tolerance test. Results. A single
      60 mg dose of denosumab efficiently inhibited serum alkaline phosphatase while it
      did not exert any significant variation in fasting glucose, insulin, or HOMA-IR
      at both 4 and 12 weeks. No changes could be detected in glucose response to the
      glucose load, Matsuda Index, or insulinogenic index. Nonetheless, 60 mg denosumab
      induced a significant reduction in the hepatic insulin resistance index at 4
      weeks and in HbA1c levels at 12 weeks. Conclusions. A single 60 mg dose of
      denosumab might positively affect hepatic insulin sensitivity though it does not
      induce clinical evident glucose metabolic disruption in nondiabetic patients. 

PMID- 25873953
TI  - Osteopetrosis and its relevance for the discovery of new functions associated
      with the skeleton.
AB  - Osteopetrosis is a rare genetic disorder characterized by an increase of bone
      mass due to defective osteoclast function. Patients typically displayed
      spontaneous fractures, anemia, and in the most severe forms hepatosplenomegaly
      and compression of cranial facial nerves leading to deafness and blindness.
      Osteopetrosis comprises a heterogeneous group of diseases as several forms are
      known with different models of inheritance and severity from asymptomatic to
      lethal. This review summarizes the genetic and clinical features of
      osteopetrosis, emphasizing how recent studies of this disease have contributed to
      understanding the central role of the skeleton in the whole body physiology. In
      particular, the interplay of bone with the stomach, insulin metabolism, male
      fertility, the immune system, bone marrow, and fat is described. 

PMID- 25873954
TI  - The association of metabolic syndrome and urolithiasis.
AB  - There has been an increasing prevalence of kidney stones over the last 2 decades
      worldwide. Many studies have indicated a possible association between metabolic
      syndrome and kidney stone disease, particularly in overweight and obese patients.
      Many different definitions of metabolic syndrome have been suggested by various
      organizations, although the definition by the International Diabetes Federation
      (IDF) is universally considered as the most acceptable definition. The IDF
      definition revolves around 4 core components: obesity, dyslipidemia,
      hypertension, and diabetes mellitus. Several hypotheses have been proposed to
      explain the pathophysiology of urolithiasis resulting from metabolic syndrome,
      amongst which are the insulin resistance and Randall's plaque hypothesis.
      Similarly the pathophysiology of calcium and uric acid stone formation has been
      investigated to determine a connection between the two conditions. Studies have
      found many factors contributing to urolithiasis in patients suffering from
      metabolic syndrome, out of which obesity, overweight, and sedentary lifestyles
      have been identified as major etiological factors. Primary and secondary
      prevention methods therefore tend to revolve mainly around lifestyle
      improvements, including dietary and other preventive measures. 

PMID- 25873955
TI  - Sex, Prescribing Practices and Guideline Recommended, Blood Pressure, and LDL
      Cholesterol Targets at Baseline in the BARI 2D Trial.
AB  - Background. Research has shown less aggressive treatment and poorer control of
      cardiovascular disease (CVD) risk factors in women than men. Methods. We analyzed
      sex differences in pharmacotherapy strategies and attainment of goals for
      hemoglobin A1c (HbA1c), blood pressure (BP), and low density lipoprotein
      cholesterol (LDL-C) in patients with type 2 diabetes and established coronary
      artery disease enrolled into the BARI 2D trial. Results. Similar numbers of drugs
      were prescribed in both women and men. Women were less frequent on metformin or
      sulfonylurea and more likely to take insulin and to be on higher doses of
      hydroxymethylglutaryl-CoA reductase inhibitors (statins) than men. After
      adjusting for baseline differences and treatment prescribed, women were less
      likely to achieve goals for HbA1c (OR = 0.71, 95% CI 0.57, 0.88) and LDL-C (OR =
      0.64, 95% CI 0.53, 0.78). More antihypertensives were prescribed to women, and
      yet BP <= 130/80 mmHg did not differ by sex. Conclusions. Women entering the BARI
      2D trial were as aggressively treated with drugs as men. Despite equivalent
      treatment, women less frequently met targets for HbA1c and LDL-C. Our findings
      suggest that there may be sex differences in response to drug therapies used to
      treat diabetes, hypertension, and hyperlipidemia.

PMID- 25873956
TI  - Functional diversity of fibroblast growth factors in bone formation.
AB  - The functional significance of fibroblast growth factor (FGF) signaling in bone
      formation has been demonstrated through genetic loss-of-function and gain-of
      function approaches. FGFs, comprising 22 family members, are classified into
      three subfamilies: canonical, hormone-like, and intracellular. The former two
      subfamilies activate their signaling pathways through FGF receptors (FGFRs).
      Currently, intracellular FGFs appear to be primarily involved in the nervous
      system. Canonical FGFs such as FGF2 play significant roles in bone formation, and
      precise spatiotemporal control of FGFs and FGFRs at the transcriptional and
      posttranscriptional levels may allow for the functional diversity of FGFs during
      bone formation. Recently, several research groups, including ours, have shown
      that FGF23, a member of the hormone-like FGF subfamily, is primarily expressed in
      osteocytes/osteoblasts. This polypeptide decreases serum phosphate levels by
      inhibiting renal phosphate reabsorption and vitamin D3 activation, resulting in
      mineralization defects in the bone. Thus, FGFs are involved in the positive and
      negative regulation of bone formation. In this review, we focus on the reciprocal
      roles of FGFs in bone formation in relation to their local versus systemic
      effects. 

PMID- 25873958
TI  - Soluble alpha -Klotho Serum Levels in Chronic Kidney Disease.
AB  - Transmembrane alpha-Klotho (TM-Klotho), expressed in renal tubules, is a cofactor
      for FGF23-receptor. Circulating soluble-alpha-Klotho (s-Klotho) results from TM
      Klotho shedding and acts on Phosphate (P) and Calcium (Ca) tubular transport.
      Decreased TM-Klotho, described in experimental chronic kidney disease (CKD),
      prevents actions of FGF23 and lessens circulating s-Klotho. Thus, levels of s
      Klotho could represent a marker of CKD-MBD. To evaluate the clinical significance
      of s-Klotho in CKD we assayed serum s-Klotho and serum FGF23 in 68 patients (age
      58 +/- 15; eGFR 45 +/- 21 mL/min). s-Klotho was lower than normal (519 +/- 183
      versus 845 +/- 330 pg/mL, P < .0001) in renal patients and its reduction was
      detectable since CKD stage 2 (P < .01). s-Klotho correlated positively with eGFR
      and serum calcium (Cas) and negatively with serum phosphate (Ps), PTH and FGF23.
      FGF23 was higher than normal (73 +/- 51 versus 36 +/- 11, P < .0002) with
      significantly increased levels since CKD stage 2 (P < .001). Our data indicate a
      negative effect of renal disease on circulating s-Klotho starting very early in
      CKD. Assuming that s-Klotho mirrors TM-Klotho synthesis, low circulating s-Klotho
      seems to reflect the ensuing of tubular resistance to FGF23, which, accordingly,
      is increased. We endorse s-Klotho as an early marker of CKD-MBD. 

PMID- 25873957
TI  - Skeleton and glucose metabolism: a bone-pancreas loop.
AB  - Bone has been considered a structure essential for mobility, calcium homeostasis,
      and hematopoietic function. Recent advances in bone biology have highlighted the
      importance of skeleton as an endocrine organ which regulates some metabolic
      pathways, in particular, insulin signaling and glucose tolerance. This review
      will point out the role of bone as an endocrine "gland" and, specifically, of
      bone-specific proteins, as the osteocalcin (Ocn), and proteins involved in bone
      remodeling, as osteoprotegerin, in the regulation of insulin function and glucose
      metabolism. 

PMID- 25873959
TI  - Sex differences in cardiovascular mortality in diabetics and nondiabetic
      subjects: a population-based study (Italy).
AB  - The objective of this study is to assess the impact of diabetes on cardiovascular
      mortality, focusing on sex differences. The inhabitants of Reggio Emilia province
      on December 31, 2009, aged 20-84 were followed up for three years for mortality.
      The exposure was determined using Reggio Emilia diabetes register. The age
      adjusted death rates were estimated as well as the incidence rate ratios using
      Poisson regression model. Interaction terms for diabetes and sex were tested by
      the Wald test. People with diabetes had an excess of mortality, compared with
      nondiabetic subjects (all cause: IRR = 1.68; 95%CI 1.60-1.78; CVD: IRR = 1.61;
      95%CI 1.47-1.76; AMI: IRR = 1.59; 95%CI 1.27-1.99; renal causes: IRR = 1.71;
      95%CI 1.22-2.38). The impact of diabetes is greater in females than males for all
      causes (P = 0.0321) and for CVD, IMA, and renal causes. Further studies are
      needed to investigate whether the difference in cardiovascular risk profile or in
      the quality of care delivered justifies the higher excess of mortality in females
      with diabetes compared to males. 

PMID- 25873960
TI  - Age- and Gender-Related Differences in LDL-Cholesterol Management in Outpatients
      with Type 2 Diabetes Mellitus.
AB  - Background. Dyslipidemia contribute to the excess of coronary heart disease (CHD)
      risk observed in women with type 2 diabetes (T2DM). Low density lipoprotein
      cholesterol (LDL-C) is the major target for CHD prevention, and T2DM women seem
      to reach LDL-C targets less frequently than men. Aim. To explore age- and gender
      related differences in LDL-C management in a large sample of outpatients with
      T2DM. Results. Overall, 415.294 patients (45.3% women) from 236 diabetes centers
      in Italy were included. Women were older and more obese, with longer diabetes
      duration, higher total-cholesterol, LDL-C, and HDL-C serum levels compared to men
      (P < 0.0001). Lipid profile was monitored in ~75% of subjects, women being
      monitored less frequently than men, irrespective of age. More women did not reach
      the LDL-C target as compared to men, particularly in the subgroup treated with
      lipid-lowering medications. The between-genders gap in reaching LDL-C targets
      increased with age and diabetes duration, favouring men in all groups.
      Conclusions. LDL-C management is worst in women with T2DM, who are monitored and
      reach targets less frequently than T2DM men. Similarly to men, they do not
      receive medications despite high LDL-C. These gender discrepancies increase with
      age and diabetes duration, exposing older women to higher CHD risk. 

PMID- 25873962
TI  - Arsenic, Antimony, Chromium, and Thallium Speciation in Water and Sediment
      Samples with the LC-ICP-MS Technique.
AB  - Chemical speciation is a very important subject in the environmental protection,
      toxicology, and chemical analytics due to the fact that toxicity, availability,
      and reactivity of trace elements depend on the chemical forms in which these
      elements occur. Research on low analyte levels, particularly in complex matrix
      samples, requires more and more advanced and sophisticated analytical methods and
      techniques. The latest trends in this field concern the so-called hyphenated
      techniques. Arsenic, antimony, chromium, and (underestimated) thallium attract
      the closest attention of toxicologists and analysts. The properties of those
      elements depend on the oxidation state in which they occur. The aim of the
      following paper is to answer the question why the speciation analytics is so
      important. The paper also provides numerous examples of the hyphenated technique
      usage (e.g., the LC-ICP-MS application in the speciation analysis of chromium,
      antimony, arsenic, or thallium in water and bottom sediment samples). An
      important issue addressed is the preparation of environmental samples for
      speciation analysis. 

PMID- 25873961
TI  - Bone Regulates Glucose Metabolism as an Endocrine Organ through Osteocalcin.
AB  - Skeleton was considered as a dynamic connective tissue, which was essential for
      mobility, calcium homeostasis, and hematopoietic niche. However more and more
      evidences indicate that skeleton works not only as a structural scaffold but also
      as an endocrine organ, which regulates several metabolic processes. Besides
      osteoprotegerin (OPG), sclerostin (SOST), and Dickopf (DKK) which play essential
      roles in bone formation, modelling, remodelling, and homeostasis, bone can also
      secret hormones, such as osteocalcin (OCN), which promotes proliferation of beta
      cells, insulin secretion, and insulin sensitivity. Additionally OCN can also
      regulate the fat cells and male gonad endocrine activity and be regulated by
      insulin and the neural system. In summary, skeleton has endocrine function via
      OCN and plays an important role in energy metabolism, especially in glucose
      metabolism. 

PMID- 25873963
TI  - A Rapid and Accurate Extraction Procedure for Analysing Free Amino Acids in Meat
      Samples by GC-MS.
AB  - This study evaluated the use of a mixer mill as the homogenization tool for the
      extraction of free amino acids in meat samples, with the main goal of analyzing a
      large number of samples in the shortest time and minimizing sample amount and
      solvent volume. Ground samples (0.2 g) were mixed with 1.5 mL HCl 0.1 M and
      homogenized in the mixer mill. The final biphasic system was separated by
      centrifugation. The supernatant was deproteinized, derivatized and analyzed by
      gas chromatography. This procedure showed a high extracting ability, especially
      in samples with high free amino acid content (recovery = 88.73-104.94%). It also
      showed a low limit of detection and quantification (3.8 . 10(-4)-6.6 . 10(-4) MUg
      MUL(-1) and 1.3 . 10(-3)-2.2 . 10(-2) MUg MUL(-1), resp.) for most amino acids,
      an adequate precision (2.15-20.15% for run-to-run), and a linear response for all
      amino acids (R (2) = 0.741-0.998) in the range of 1-100 ug mL(-1). Moreover, it
      takes less time and requires lower amount of sample and solvent than conventional
      techniques. Thus, this is a cost and time efficient tool for homogenizing in the
      extraction procedure of free amino acids from meat samples, being an adequate
      option for routine analysis. 

PMID- 25873964
TI  - Pregabalin and tranexamic Acid evaluation by two simple and sensitive
      spectrophotometric methods.
AB  - This paper demonstrates colorimetric visible spectrophotometric quantification
      methods for amino acid, namely, tranexamic acid and pregabalin. Both drugs
      contain the amino group, and when they are reacted with 2,4-dinitrophenol and
      2,4,6-trinitrophenol, they give rise to yellow colored complexes showing
      absorption maximum at 418 nm and 425 nm, respectively, based on the Lewis acid
      base reaction. Detailed optimization process and stoichiometric studies were
      conducted along with investigation of thermodynamic features, that is,
      association constant and standard free energy changes. The method was linear over
      the concentration range of 0.02-200 ugmL(-1) with correlation coefficient of more
      than 0.9990 in all of the cases. Limit of detection was in range from 0.0041 to
      0.0094 ugmL(-1) and limit of quantification was in the range from 0.0137 to
      0.0302 ugmL(-1). Excellent recovery in Placebo spiked samples indicated that
      there is no interference from common excipients. The analytical methods under
      proposal were successfully applied to determine tranexamic acid and pregabalin in
      commercial products. t-test and F ratio were evaluated without noticeable
      difference between the proposed and reference methods. 

PMID- 25873965
TI  - Application of an activated carbon-based support for magnetic solid phase
      extraction followed by spectrophotometric determination of tartrazine in
      commercial beverages.
AB  - A method is presented for magnetic solid phase extraction of tartrazine from
      nonalcoholic beverages. The method involves the extraction and clean-up by
      activated carbon covered with magnetite dispersed in the sample, followed by the
      magnetic isolation and desorption of the analyte by basified methanol. The
      tartrazine eluted from the magnetic support was determined by spectrophotometry.
      Under optimal conditions, the linear range of the calibration curve ranges from 3
      to 30 mg L(-1), with a limit of detection of 1 mg L(-1). The method was validated
      by comparing the results with those obtained by HPLC. A precision of <5.0% was
      obtained in all cases and no significant differences were observed (P < 0.05). 

PMID- 25873966
TI  - QuEChERS Method Followed by Solid Phase Extraction Method for Gas Chromatographic
      Mass Spectrometric Determination of Polycyclic Aromatic Hydrocarbons in Fish.
AB  - A gas chromatography equipped with mass spectrometer (GCMS) method was developed
      and validated for determination of 16 polycyclic aromatic hydrocarbons (PAHs) in
      fish using modified quick, easy, cheap, effective, rugged, and safe (QuEChERS)
      method for extraction and solid phase extraction for sample cleanup to remove
      most of the coextract combined with GCMS for determination of low concentration
      of selected group of PAHs in homogenized fish samples. PAHs were separated on a
      GCMS with HP-5ms Ultra Inert GC Column (30 m, 0.25 mm, and 0.25 um). Mean
      recovery ranged from 56 to 115%. The extraction efficiency was consistent over
      the entire range where indeno(1,2,3-cd)pyrene and benzo(g,h,i)perylene showed
      recovery (65, 69%), respectively, at 2 ug/kg. No significant dispersion of
      results was observed for the other remaining PAHs and recovery did not differ
      substantially, and at the lowest and the highest concentrations mean recovery and
      RSD% showed that most of PAHs were between 70% and 120% with RSD less than 10%.
      The measurement uncertainty is expressed as expanded uncertainty and in terms of
      relative standard deviation (at 95% confidence level) is +/-12%. This method is
      suitable for laboratories engaged daily in routine analysis of a large number of
      samples. 

PMID- 25873967
TI  - A High Throughput Method for Measuring Polycyclic Aromatic Hydrocarbons in
      Seafood Using QuEChERS Extraction and SBSE.
AB  - National Oceanic and Atmospheric Administration (NOAA) Method NMFS-NWFSC-59 2004
      is currently used to quantitatively analyze seafood for polycyclic aromatic
      hydrocarbon (PAH) contamination, especially following events such as the
      Deepwater Horizon oil rig explosion that released millions of barrels of crude
      oil into the Gulf of Mexico. This method has limited throughput capacity; hence,
      alternative methods are necessary to meet analytical demands after such events.
      Stir bar sorptive extraction (SBSE) is an effective technique to extract trace
      PAHs in water and the quick, easy, cheap, effective, rugged, and safe (QuEChERS)
      extraction strategy effectively extracts PAHs from complex food matrices. This
      study uses SBSE to concentrate PAHs and eliminate matrix interference from
      QuEChERS extracts of seafood, specifically oysters, fish, and shrimp. This method
      provides acceptable recovery (65-138%) linear calibrations and is sensitive (LOD
      = 0.02 ppb, LOQ = 0.06 ppb) while providing higher throughput and maintaining
      equivalency between NOAA 2004 as determined by analysis of NIST SRM 1974b mussel
      tissue. 

PMID- 25873968
TI  - Extraction of HCV-RNA from Plasma Samples: Development towards Semiautomation.
AB  - A semiautomated extraction protocol of HCV-RNA using Favorgen RNA extraction kit
      has been developed. The kit provided protocol was modified by replacing manual
      spin steps with vacuum filtration. The assay performance was evaluated by real
      time qPCR based on Taqman technology. Assay linearity was confirmed with the
      serial dilutions of RTA (Turkey) containing 1 * (10(6), 10(5), 10(4), and 10(3))
      IU mL(-1). Comparison of test results obtained by two extraction methods showed a
      good correlation (r = 0.95, n = 30) with detection limit of 10(2) IU mL(-1). The
      semiautomated vacuum filtration based protocol demonstrated high throughput: 35
      minutes for the extraction of a batch of 30 samples (150 uL each) with reduced
      labor, time, waste, and cost. Performance characteristics of semiautomated system
      make it suitable for use in diagnostic purpose and viral load determinations. 

PMID- 25873969
TI  - An Optimized High Throughput Clean-Up Method Using Mixed-Mode SPE Plate for the
      Analysis of Free Arachidonic Acid in Plasma by LC-MS/MS.
AB  - A high throughput sample preparation method was developed utilizing mixed-mode
      solid phase extraction (SPE) in 96-well plate format for the determination of
      free arachidonic acid in plasma by LC-MS/MS. Plasma was mixed with 3% aqueous
      ammonia and loaded into each well of 96-well plate. After washing with water and
      methanol sequentially, 3% of formic acid in acetonitrile was used to elute
      arachidonic acid. The collected fraction was injected onto a reversed phase
      column at 30 degrees C with mobile phase of acetonitrile/water (70 : 30, v/v) and
      detected by LC-MS/MS coupled with electrospray ionization (ESI) in multiple
      reaction monitoring (MRM) mode. The calibration curve ranged from 10 to 2500
      ng/mL with sufficient linearity (r (2) = 0.9999). The recoveries were in the
      range of 99.38% to 103.21% with RSD less than 6%. The limit of detection is 3
      ng/mL. 

PMID- 25873970
TI  - Comparison of electrospray ionization and atmospheric chemical ionization coupled
      with the liquid chromatography-tandem mass spectrometry for the analysis of
      cholesteryl esters.
AB  - The approach of two different ionization techniques including electrospray
      ionization (ESI) and atmospheric pressure chemical ionization (APCI) coupled with
      liquid chromatography-tandem mass spectrometry (LC-MS/MS) was tested for the
      analysis of cholesteryl esters (CEs). The retention time (RT), signal intensity,
      protonated ion, and product ion of CEs were compared between ESI and APCI. RT of
      CEs from both ionizations decreased with increasing double bonds, while it
      increased with longer carbon chain length. The ESI process generated strong
      signal intensity of precursor ions corresponding to [M+Na](+) and [M+NH4](+)
      regardless of the number of carbon chains and double bonds in CEs. On the other
      hand, the APCI process produced a protonated ion of CEs [M+H](+) with a weak
      signal intensity, and it is selectively sensitive to detect precursor ions of CEs
      with unsaturated fatty acids. The ESI technique proved to be effective in
      ionizing more kinds of CEs than the APCI technique. 

PMID- 25873971
TI  - Dramatic improvement of proteomic analysis of zebrafish liver tumor by effective
      protein extraction with sodium deoxycholate and heat denaturation.
AB  - Majority of the proteomic studies on tissue samples involve the use of gel-based
      approach for profiling and digestion. The laborious gel-based approach is slowly
      being replaced by the advancing in-solution digestion approach. However, there
      are still several difficulties such as difficult-to-solubilize proteins, poor
      proteomic analysis in complex tissue samples, and the presence of sample
      impurities. Henceforth, there is a great demand to formulate a highly efficient
      protein extraction buffer with high protein extraction efficiency from tissue
      samples, high compatibility with in-solution digestion, reduced number of sample
      handling steps to reduce sample loss, low time consumption, low cost, and ease of
      usage. Here, we evaluated various existing protein extraction buffers with
      zebrafish liver tumor samples and found that sodium deoxycholate- (DOC-) based
      extraction buffer with heat denaturation was the most effective approach for
      highly efficient extraction of proteins from complex tissues such as the
      zebrafish liver tumor. A total of 4,790 proteins have been identified using
      shotgun proteomics approach with 2D LC, which to our knowledge is the most
      comprehensive study for zebrafish liver tumor proteome. 

PMID- 25873972
TI  - Sample Preparation and Extraction in Small Sample Volumes Suitable for Pediatric
      Clinical Studies: Challenges, Advances, and Experiences of a Bioanalytical HPLC
      MS/MS Method Validation Using Enalapril and Enalaprilat.
AB  - In USA and Europe, medicines agencies force the development of child-appropriate
      medications and intend to increase the availability of information on the
      pediatric use. This asks for bioanalytical methods which are able to deal with
      small sample volumes as the trial-related blood lost is very restricted in
      children. Broadly used HPLC-MS/MS, being able to cope with small volumes, is
      susceptible to matrix effects. The latter restrains the precise drug
      quantification through, for example, causing signal suppression. Sophisticated
      sample preparation and purification utilizing solid-phase extraction was applied
      to reduce and control matrix effects. A scale-up from vacuum manifold to positive
      pressure manifold was conducted to meet the demands of high-throughput within a
      clinical setting. Faced challenges, advances, and experiences in solid-phase
      extraction are exemplarily presented on the basis of the bioanalytical method
      development and validation of low-volume samples (50 MUL serum). Enalapril,
      enalaprilat, and benazepril served as sample drugs. The applied sample
      preparation and extraction successfully reduced the absolute and relative matrix
      effect to comply with international guidelines. Recoveries ranged from 77 to 104%
      for enalapril and from 93 to 118% for enalaprilat. The bioanalytical method
      comprising sample extraction by solid-phase extraction was fully validated
      according to FDA and EMA bioanalytical guidelines and was used in a Phase I study
      in 24 volunteers. 

PMID- 25873973
TI  - Antibacterial, Antifungal, and Insecticidal Potentials of Oxalis corniculata and
      Its Isolated Compounds.
AB  - Oxalis corniculata is a common medicinal plant widely used against numerous
      infectious diseases. The agrochemical potential of methanolic extract, n-hexane,
      chloroform, ethyl acetate, and n-butanol fractions were assessed to measure the
      antibacterial, antifungal, and insecticidal activities of the plant. The crude,
      chloroform, and n-butanol soluble fractions showed excellent activities against
      Escherichia coli, Shigella dysenteriae, Salmonella typhi, and Bacillus subtilis
      but have no activity against Staphylococcus aureus. Similarly the crude, n
      hexane, and chloroform fractions were also found to have significant activity
      against fungal strains including Fusarium solani, Aspergillus flexneri, and
      Aspergillus flavus and have no activity against Aspergillus niger. Chemical
      pesticides have shown very good results at the beginning, but with the passage of
      time the need was realized to use the natural plant sources for the safe control
      of insects. The current study will provide minor contribution towards it. High
      mortality rate was recorded for the crude extract and chloroform fraction against
      Tribolium castaneum. The two isolated compounds 5-hydroxy-6,7,8,4'
      tetramethoxyflavone (1) and 5,7,4'-trihydroxy-6,8-dimethoxyflavone (2) were
      evaluated for antibacterial, antifungal, and insecticidal activities. The results
      showed that compound 2 was more active than compound 1 against the tested
      bacterial strains and insects. 

PMID- 25873974
TI  - Alternate sequential suture tightening: a novel technique for uncontrolled
      postpartum hemorrhage.
AB  - Objective. The most commonly described technique of modified B-Lynch suture may
      not be suitable for all the patients presenting with flabby, atonic uterus. Study
      Design. A retrospective analysis of twelve patients with uncontrolled postpartum
      haemorrhage, who underwent this procedure from March 2007 to September 2012, was
      conducted. In this novel technique, sutures are passed in the lower uterine
      segment and are tightened alternately to control uterine bleeding. Results.
      Average duration of the procedure was 4 minutes (range 2-7 minutes). Average
      blood loss was 1625 mL (range 1300-1900 mL). Eleven patients (91.66%) were seen
      to have a successful outcome with only this technique. No patient required
      hysterectomy and one patient (8.33%) required additional bilateral internal iliac
      artery ligation. All the patients had a minimum follow-up of 2 yrs and none of
      them reported any infertility problems. Conclusion. This technique is simple,
      quick, and effective. There was no adverse effect on the fertility potential for
      the observed 2 years; however, a long-term follow-up is required to comment on
      its actual rate. This technique cannot replace the standard modified B-Lynch
      technique for uncontrolled postpartum haemorrhage but can be used for
      unresponsive, flabby, and atonic uterus. 

PMID- 25873975
TI  - Balloon Dilatation of a Case of Tuberculous Tracheobronchial Stenoses during the
      Course of Antituberculous Treatment.
AB  - We report a case of posttuberculosis (TB) tracheobronchial stenoses presented
      with progressive exertional dyspnea during the course of anti-TB treatment. An 83
      year-old Japanese man was admitted for progressive dyspnea; chest X-ray and CT
      showed stenosis of distal trachea and left main bronchus. Pulmonary function test
      revealed reduction of FEV1. Balloon dilatation without stent insertion was the
      choice for this patient for multiple reasons with marked improvement of symptoms.

PMID- 25873976
TI  - A new family with an activating mutation (G431S) in the TSH receptor gene: a
      phenotype discussion and review of the literature.
AB  - Germline nonautoimmune hyperthyroidism due to an activating mutation in the
      thyroid stimulating hormone receptor gene is an uncommon disease. To date 32
      different mutations have been described. The severity of the hyperthyroid
      symptoms is variable and phenotype differences have been described in subjects
      harboring the same mutation. This paper describes a family with a mutation in
      codon 431 of the thyroid stimulating hormone receptor gene. This is the most
      common activating mutation in the thyroid stimulating hormone receptor gene with
      total of 13 patients harboring the mutation in four families. The similarities
      and differences among patients with the mutation in codon 431 are discussed.
      Furthermore all previously reported activating mutations in the thyroid
      stimulating hormone receptor gene are reviewed. 

PMID- 25873977
TI  - Sensitization to workplace respiratory allergens among bakery workers in Douala,
      Cameroon: a cross-sectional study.
AB  - BACKGROUND: Sensitization to flour or fungal alpha-amylase is a prerequisite for
      the development of respiratory allergy in bakers. The knowledge of occupational
      allergen sensitization among bakery workers will facilitate the implementation of
      preventive measures for respiratory allergies in bakeries. The objective of this
      study was to determine the prevalence and factors associated with sensitization
      to wheat flour and alpha-amylase in bakers in Douala. METHODS: A cross-sectional
      study was conducted in 42 of the 151 bakeries that are present in the city of
      Douala. Demographics, clinical data, as well as results of skin prick tests to
      wheat flour, alpha-amylase and common aeroallergens were collected from all
      participants. A logistic regression model of the SPSS.20 software was used to
      identify factors associated with sensitization to wheat flour and alpha-amylase.
      RESULTS: Of the 229 participants included in the study, 222 (96.9%) were male.
      The mean age was 36.3 +/- 8.9 years. The prevalence of sensitization to flour and
      alpha-amylase were 16.6% and 8.3% respectively. After multivariate analysis,
      factors associated with sensitization to flour were work seniority and
      sensitization to storage mites while an age of 30 years and above was the only
      factor associated with sensitization to alpha-amylase. CONCLUSION: Bakers in
      Douala are at risk of sensitization to occupational allergens. The environmental
      hygiene in bakeries, health surveillance and the use of personal protective
      equipment could reduce the risk of respiratory allergies among bakers.

PMID- 25873980
TI  - Acupuncture and oxidative stress.

PMID- 25873979
TI  - Alterations in Salivary Proteome following Single Twenty-Minute Session of Yogic
      Breathing.
AB  - Yogic breathing (YB) has been suggested to reduce stress and blood pressure and
      increase cognitive processes. However, alterations after YB at the molecular
      level are not well established. Twenty healthy volunteers were randomized into
      two groups (N = 10 per group): YB or attention controls (AC). The YB group
      performed two YB exercises, each for ten minutes, for a total of twenty minutes
      in a single session. AC group read a text of their choice for 20 minutes. Saliva
      was collected at baseline and at 5, 10, 15, and 20 minutes. Using Mass
      Spectrometry (MS), we initially found that 22 proteins were differentially
      expressed and then validated deleted in malignant brain tumor-1 (DMBT1) and Ig
      lambda-2 chain C region (IGLC2) using Western Blotting. DMBT1 was elevated in 7
      of YB group by 10-fold and 11-fold at 10 and 15 minutes, respectively, whereas it
      was undetectable in the time-matched AC group (P < 0.05). There was a significant
      interaction between groups and time assessed by two-way ANOVA (P < 0.001). IGLC2
      also showed a significant increase in YB group as measured by Western Blotting.
      These data are the first to demonstrate the feasibility of stimulating and
      detecting salivary protein biomarkers in response to an acute Yoga exercise. This
      trial is registered with ClincalTrials.gov NCT02108769. 

PMID- 25873978
TI  - Antifungal and antibacterial metabolites from a French poplar type propolis.
AB  - During this study, the in vitro antifungal and antibacterial activities of
      different extracts (aqueous and organic) obtained from a French propolis batch
      were evaluated. Antifungal activity was evaluated by broth microdilution on three
      pathogenic strains: Candida albicans, C. glabrata, and Aspergillus fumigatus.
      Antibacterial activity was assayed using agar dilution method on 36 Gram-negative
      and Gram-positive strains including Staphylococcus aureus. Organic extracts
      showed a significant antifungal activity against C. albicans and C. glabrata
      (MIC80 between 16 and 31 ug/mL) but only a weak activity towards A. fumigatus
      (MIC80 = 250 ug/mL). DCM based extracts exhibited a selective Gram-positive
      antibacterial activity, especially against S. aureus (SA) and several of its
      methicillin-resistant (MRSA) and methicillin-susceptible (MSSA) strains (MIC100
      30-97 ug/mL). A new and active derivative of catechin was also identified whereas
      a synergistic antimicrobial effect was noticed during this study. 

PMID- 25873981
TI  - Medicinal plants in management of type 2 diabetes and neurodegenerative
      disorders.

PMID- 25873983
TI  - Different Proportions of Huangqi (Radix Astragali Mongolici) and Honghua (Flos
      Carthami) Injection on alpha-Glucosidase and alpha-Amylase Activities.
AB  - Objective. To study the effect of different proportions of Huangqi (Radix
      Astragali Mongolici) and Honghua (Flos Carthami) injection on alpha-glucosidase
      and alpha-amylase activity simultaneously. Methods. The injections were prepared
      according to the standards of the China Food and Drug Administration. The assay
      for potential alpha-glucosidase inhibitors was based on the hydrolysis of 4
      methylumbelliferyl-alpha-D-glucopyranoside (4-MUG). The alpha-amylase EnzChek
      assay kit was used to determine potential alpha-amylase inhibitors. Acarbose was
      the positive control. Results. The half maximal (50%) inhibitory concentration
      (IC50) of acarbose against alpha-glucosidase and alpha-amylase was (1.8 +/- 0.4)
      MUg/mL and (227 +/- 32) MUg/mL, respectively. Honghua showed significant
      inhibition of alpha-glucosidase activity compared with Huangqi (P < 0.01).
      Honghua inhibited alpha-amylase activity, but Huangqi did not. IC50s for alpha
      glucosidase inhibition by mixtures at 10 : 1, 5 : 1, and 2 : 1 were significantly
      lower than those at the 20 : 1 mixture (P < 0.01). alpha-Amylase inhibition by
      the 2 : 1 mixture was significantly higher than that by the 20 : 1, 10 : 1, and 5
      : 1 mixtures at 500 MUg/mL and 1000 MUg/mL (P < 0.01), with 5 : 1 significantly
      higher than 20 : 1 and 10 : 1 at 1000 MUg/mL (P < 0.01). Conclusion. Honghua
      significantly inhibited alpha-glucosidase activity compared with Huangqi (P <
      0.01). For simultaneous inhibition of alpha-glucosidase and alpha-amylase
      activities, the mixtures at 2 : 1 and 5 : 1 exhibited significant effects
      compared with those at 20 : 1 (P < 0.01). 

PMID- 25873982
TI  - alpha-Mangostin Improves Glucose Uptake and Inhibits Adipocytes Differentiation
      in 3T3-L1 Cells via PPARgamma, GLUT4, and Leptin Expressions.
AB  - Obesity has been often associated with the occurrence of cardiovascular diseases,
      type 2 diabetes, and cancer. The development of obesity is also accompanied by
      significant differentiation of preadipocytes into adipocytes. In this study, we
      investigated the activity of alpha-mangostin, a major xanthone component isolated
      from the stem bark of G. malaccensis, on glucose uptake and adipocyte
      differentiation of 3T3-L1 cells focusing on PPARgamma, GLUT4, and leptin
      expressions. alpha-Mangostin was found to inhibit cytoplasmic lipid accumulation
      and adipogenic differentiation. Cells treated with 50 MUM of alpha-mangostin
      reduced intracellular fat accumulation dose-dependently up to 44.4% relative to
      MDI-treated cells. Analyses of 2-deoxy-D-[(3)H] glucose uptake activity showed
      that alpha-mangostin significantly improved the glucose uptake (P < 0.05) with
      highest activity found at 25 MUM. In addition, alpha-mangostin increased the
      amount of free fatty acids (FFA) released. The highest glycerol release level was
      observed at 50 MUM of alpha-mangostin. qRT-PCR analysis showed reduced lipid
      accumulation via inhibition of PPARgamma gene expression. Induction of glucose
      uptake and free fatty acid release by alpha-mangostin were accompanied by
      increasing mRNA expression of GLUT4 and leptin. These evidences propose that
      alpha-mangostin might be possible candidate for the effective management of
      obesity in future. 

PMID- 25873984
TI  - Risky HIV sexual behaviour and depression among University of Nairobi students.
AB  - BACKGROUND: Prevalence rates of human immunodeficiency virus (HIV) infection
      among the youth are disproportionately high compared to that of other age groups
      in Kenya. Poor mental health has been linked to risky HIV behaviour, yet few
      local studies have explored these aspects. This study sought to determine
      associations between HIV risky sexual behaviour and depression among
      undergraduate students at the University of Nairobi. METHOD: A random sample of
      923 (525 males and 365 females) undergraduate students was interviewed using a
      questionnaire to record sociodemographic variables and risky sexual behaviour
      including having multiple sexual partners, inconsistent condom use and engaging
      in sex after drinking. Depressive symptoms were measured using the Centre for
      Epidemiological Studies Short Depression Scale (CES-D 10). RESULTS: The students'
      mean age was 23 years (s.d.4.0). Overall, 41.33% of the students scored above the
      cut-off point of 10 on the CES-D 10 scale, with 35.71% having moderate symptoms
      and 5.62% having severe depressive symptoms. The percentage of those who had ever
      been diagnosed with sexually transmitted infections (STIs) was 9.71% (males
      8.65%; females 11.01%); and for HIV 3.04% (males 2.02%; females 4.05%). Nearly
      30% reported having had multiple partners in the previous 12 months, 27.4% of the
      students did not use condoms with sexual partners and 21% had engaged in sex
      after drinking within the previous 3 months. In multivariable-bivariate logistic
      regression, being older, having depressive symptoms, alcohol use/binge drinking,
      tobacco use, sex after drinking, previous diagnosis of STI, physical abuse,
      sexual coercion and history of sexual abuse as a child were significantly
      associated with having multiple partners. Further, younger age, being female,
      tobacco use and previous diagnosis of STI were significantly associated with
      inconsistent condom use. CONCLUSION: The prevalence of HIV rate infection is low
      compared to the national average but risky sexual behaviour is common among the
      students and is positively linked to depressive symptoms among other factors.
      Programmes aimed at HIV prevention should be integrated with mental health
      interventions.

PMID- 25873985
TI  - Investing in breastfeeding - the world breastfeeding costing initiative.
AB  - BACKGROUND: Despite scientific evidence substantiating the importance of
      breastfeeding in child survival and development and its economic benefits,
      assessments show gaps in many countries' implementation of the 2003 WHO and
      UNICEF Global Strategy for Infant and Young Child Feeding (Global Strategy).
      Optimal breastfeeding is a particular example: initiation of breastfeeding within
      the first hour of birth, exclusive breastfeeding for the first six months; and
      continued breastfeeding for two years or more, together with safe, adequate,
      appropriate, responsive complementary feeding starting in the sixth month. While
      the understanding of "optimal" may vary among countries, there is a need for
      governments to facilitate an enabling environment for women to achieve optimal
      breastfeeding. Lack of financial resources for key programs is a major
      impediment, making economic perspectives important for implementation. Globally,
      while achieving optimal breastfeeding could prevent more than 800,000 under five
      deaths annually, in 2013, US$58 billion was spent on commercial baby food
      including milk formula. Support for improved breastfeeding is inadequately
      prioritized by policy and practice internationally. METHODS: The World
      Breastfeeding Costing Initiative (WBCi) launched in 2013, attempts to determine
      the financial investment that is necessary to implement the Global Strategy, and
      to introduce a tool to estimate the costs for individual countries. The article
      presents detailed cost estimates for implementing the Global Strategy, and
      outlines the WBCi Financial Planning Tool. Estimates use demographic data from
      UNICEF's State of the World's Children 2013. RESULTS: The WBCi takes a
      programmatic approach to scaling up interventions, including policy and planning,
      health and nutrition care systems, community services and mother support, media
      promotion, maternity protection, WHO International Code of Marketing of
      Breastmilk Substitutes implementation, monitoring and research, for optimal
      breastfeeding practices. The financial cost of a program to implement the Global
      Strategy in 214 countries is estimated at US $17.5 billion ($130 per live birth).
      The major recurring cost is maternity entitlements. CONCLUSIONS: WBCi is a policy
      advocacy initiative to encourage integrated actions that enable breastfeeding.
      WBCi will help countries plan and prioritize actions and budget them accurately.
      International agencies and donors can also use the tool to calculate or track
      investments in breastfeeding.

PMID- 25873987
TI  - Motion estimation using the firefly algorithm in ultrasonic image sequence of
      soft tissue.
AB  - Ultrasonic image sequence of the soft tissue is widely used in disease diagnosis;
      however, the speckle noises usually influenced the image quality. These images
      usually have a low signal-to-noise ratio presentation. The phenomenon gives rise
      to traditional motion estimation algorithms that are not suitable to measure the
      motion vectors. In this paper, a new motion estimation algorithm is developed for
      assessing the velocity field of soft tissue in a sequence of ultrasonic B-mode
      images. The proposed iterative firefly algorithm (IFA) searches for few candidate
      points to obtain the optimal motion vector, and then compares it to the
      traditional iterative full search algorithm (IFSA) via a series of experiments of
      in vivo ultrasonic image sequences. The experimental results show that the IFA
      can assess the vector with better efficiency and almost equal estimation quality
      compared to the traditional IFSA method. 

PMID- 25873986
TI  - Effects of early feeding on growth velocity and overweight/obesity in a cohort of
      HIV unexposed South African infants and children.
AB  - BACKGROUND: South Africa has the highest prevalence of overweight/obesity in Sub
      Saharan Africa. Assessing the effect of modifiable factors such as early infant
      feeding on growth velocity and overweight/obesity is therefore important. This
      paper aimed to assess the effect of infant feeding in the transitional period (12
      weeks) on 12-24 week growth velocity amongst HIV unexposed children using WHO
      growth velocity standards and on the age and sex adjusted body mass index (BMI) Z
      score distribution at 2 years. METHODS: Data were from 3 sites in South Africa
      participating in the PROMISE-EBF trial. We calculated growth velocity Z-scores
      using the WHO growth standards and assessed feeding practices using 24-hour and 7
      day recall data. We used quantile regression to study the associations between 12
      week infant feeding and 12-24 week weight velocity (WVZ) with BMI-for-age Z-score
      at 2 years. We included the internal sample quantiles (70th and 90th centiles)
      that approximated the reference cut-offs of +2 (corresponding to overweight) and
      +3 (corresponding to obesity) of the 2 year BMI-for-age Z-scores. RESULTS: At the
      2-year visit, 641 children were analysed (median age 22 months, IQR: 17-26
      months). Thirty percent were overweight while 8.7% were obese. Children not
      breastfed at 12 weeks had higher 12-24 week mean WVZ and were more overweight and
      obese at 2 years. In the quantile regression, children not breastfed at 12 weeks
      had a 0.37 (95% CI 0.07, 0.66) increment in BMI-for-age Z-score at the 50th
      sample quantile compared to breast-fed children. This difference in BMI-for-age Z
      score increased to 0.46 (95% CI 0.18, 0.74) at the 70th quantile and 0.68 (95% CI
      0.41, 0.94) at the 90th quantile . The 12-24 week WVZ had a uniform independent
      effect across the same quantiles. CONCLUSIONS: This study demonstrates that the
      first 6 months of life is a critical period in the development of childhood
      overweight and obesity. Interventions targeted at modifiable factors such as
      early infant feeding practices may reduce the risks of rapid weight gain and
      subsequent childhood overweight/obesity.

PMID- 25873988
TI  - Identifying odd/even-order binary kernel slices for a nonlinear system using
      inverse repeat m-sequences.
AB  - The study of various living complex systems by system identification method is
      important, and the identification of the problem is even more challenging when
      dealing with a dynamic nonlinear system of discrete time. A well-established
      model based on kernel functions for input of the maximum length sequence (m
      sequence) can be used to estimate nonlinear binary kernel slices using cross
      correlation method. In this study, we examine the relevant mathematical
      properties of kernel slices, particularly their shift-and-product property and
      overlap distortion problem caused by the irregular shifting of the estimated
      kernel slices in the cross-correlation function between the input m-sequence and
      the system output. We then derive the properties of the inverse repeat (IR) m
      sequence and propose a method of using IR m-sequence as an input to separately
      estimate odd- and even-order kernel slices to reduce the chance of kernel-slice
      overlapping. An instance of third-order Wiener nonlinear model is simulated to
      justify the proposed method.

PMID- 25873989
TI  - A fingerprint encryption scheme based on irreversible function and secure
      authentication.
AB  - A fingerprint encryption scheme based on irreversible function has been designed
      in this paper. Since the fingerprint template includes almost the entire
      information of users' fingerprints, the personal authentication can be determined
      only by the fingerprint features. This paper proposes an irreversible
      transforming function (using the improved SHA1 algorithm) to transform the
      original minutiae which are extracted from the thinned fingerprint image. Then,
      Chinese remainder theorem is used to obtain the biokey from the integration of
      the transformed minutiae and the private key. The result shows that the scheme
      has better performance on security and efficiency comparing with other
      irreversible function schemes. 

PMID- 25873990
TI  - The prediction in computer color matching of dentistry based on GA+BP neural
      network.
AB  - Although the use of computer color matching can reduce the influence of
      subjective factors by technicians, matching the color of a natural tooth with a
      ceramic restoration is still one of the most challenging topics in esthetic
      prosthodontics. Back propagation neural network (BPNN) has already been
      introduced into the computer color matching in dentistry, but it has
      disadvantages such as unstable and low accuracy. In our study, we adopt genetic
      algorithm (GA) to optimize the initial weights and threshold values in BPNN for
      improving the matching precision. To our knowledge, we firstly combine the BPNN
      with GA in computer color matching in dentistry. Extensive experiments
      demonstrate that the proposed method improves the precision and prediction
      robustness of the color matching in restorative dentistry. 

PMID- 25873991
TI  - Feature quantification and abnormal detection on cervical squamous epithelial
      cells.
AB  - Feature analysis and classification detection of abnormal cells from images for
      pathological analysis are an important issue for the realization of computer
      assisted disease diagnosis. This paper studies a method for cervical squamous
      epithelial cells. Based on cervical cytological classification standard and
      expert diagnostic experience, expressive descriptors are extracted according to
      morphology, color, and texture features of cervical scales epithelial cells.
      Further, quantificational descriptors related to cytopathology are derived as
      well, including morphological difference degree, cell hyperkeratosis, and deeply
      stained degree. The relationship between quantified value and pathological
      feature can be established by these descriptors. Finally, an effective method is
      proposed for detecting abnormal cells based on feature quantification. Integrated
      with clinical experience, the method can realize fast abnormal cell detection and
      preliminary cell classification. 

PMID- 25873992
TI  - Predictive factors of Osaka Medical College (OMC) brace treatment in patients
      with adolescent idiopathic scoliosis.
AB  - BACKGROUND: Factors influencing clinical course of brace treatment apply to
      adolescent idiopathic scoliosis (AIS) patients remain unclear. By making clear
      them, we may select suitable patients for brace treatment and alleviate
      overtreatment. The purpose of this study was to explore predictive factors of
      Osaka Medical College (OMC) brace treatment for AIS patients in accordance with
      the modified standardized criteria proposed by the Scoliosis Research Society
      (SRS) committee on bracing and non-operative management. METHODS: From 1999
      through 2010, 31 consecutive patients with AIS who were newly prescribed the OMC
      brace and met the modified SRS criteria were studied. The study included 2 boys
      and 29 girls with a mean age of 12 years and 0 month. We investigated the
      clinical course and evaluated the impacts of compliance, initial brace correction
      rate, curve flexibility, curve pattern, Cobb angle, chronological age, and Risser
      stage to clinical outcomes. The clinical course of the brace treatment was
      considered progression if >=6 degrees  curvature increase occurred and
      improvement if >=6 degrees  curvature decrease occurred according to SRS judgment
      criteria. RESULTS: The curve progressed in 10 cases, the curve improved in 6
      cases, and the curve remained unchanged in 15 cases (success rate: 67.7%). The
      success rate was statistically higher in the patient group whose instruction
      adherence rate was greater than 50% as compared with in those 50% or less.
      Initial brace correction rate, curve flexibility, curve pattern, the magnitude of
      Cobb angle, chronological age, and Risser stage did not have any significant
      effect for clinical courses. However, success rate was insignificantly higher in
      the cases whose Cobb angle in brace was smaller than that in hanging position.
      CONCLUSIONS: OMC brace treatment could alter the natural history of AIS, however,
      that was significantly affected by compliance of brace wear.

PMID- 25873993
TI  - A tool to improve competence in the management of emergency patients by rural
      clinic health workers: a pilot assessment on the Thai-Myanmar border.
AB  - BACKGROUND: Shoklo Malaria Research Unit has been providing health care in remote
      clinics on the Thai-Myanmar border to refugee and migrant populations since 1986
      and 1995, respectively. Clinics are staffed by local health workers with a
      variety of training and experience. The need for a tool to improve the competence
      of local health workers in basic emergency assessment and management was
      recognised by medical faculty after observing the case mix seen at the clinic and
      reviewing the teaching programme that had been delivered in the past year (Jan-13
      to March-14). AIMS: To pilot the development and evaluation of a simple teaching
      tool to improve competence in the assessment and management of acutely unwell
      patients by local health workers that can be delivered onsite with minimal
      resources. METHODS: A structured approach to common emergencies presenting to
      rural clinics and utilizing equipment available in the clinics was developed. A
      prospective repeated-measures observed structured clinical examination (OSCE)
      assessment design was used to score participants in their competence to assess
      and manage a scenario based 'emergency patient' at baseline, immediately post
      course, and 8 weeks after the delivery of the teaching course. The assessment was
      conducted at 3 clinic sites and staff participation was voluntary. Participants
      filled out questionnaires on their confidence with different scenario based
      emergency patients. RESULTS: All staff who underwent the baseline assessment
      failed to carry out the essential steps in initial emergency assessment and
      management of an unconscious patient scenario. Following delivery of the teaching
      session, all groups showed improved competence in both objective assessment and
      subjective confidence levels. CONCLUSIONS: Structured and practical teaching and
      learning with minimal theory in this resource limited setting had a positive
      short-term effect on the competence of individual staff to carry out an initial
      assessment and manage an acutely unwell patient. Health-worker confidence
      likewise improved. Workplace assessments are needed to determine if this type of
      skills training impacts upon mortality or near miss mortality patients at the
      clinic.

PMID- 25873994
TI  - Differential systemic exposure to galangin after oral and intravenous
      administration to rats.
AB  - BACKGROUND: Galangin (3,5,7-trihydroxyflavone) is present in high concentrations
      in herbal medicine such as Alpinia officinarum Hance. Galangin shows multifaceted
      in vitro and in vivo biological activities. The number and position of hydroxyl
      groups in this molecule play an important role in these biological activities.
      However, these hydroxyl groups undergo glucuronidation and sulfation in in vitro
      assay system. However, the systemic exposure to galangin after dosing in animals
      and/or humans remains largely unknown. Thus it is not clear whether the galangin
      exists in the body at concentrations high enough for the biological effects.
      Furthermore, the metabolite identification and the corresponding plasma
      pharmacokinetics need to be characterized. RESULTS: Two LC-MS/MS methods were
      developed and validated and successfully applied to analyze the parent drug
      molecules and aglycones liberated from plasma samples via beta-glucuronidase
      hydrolysis. Our major findings were as follows: (1) The routes of administration
      showed significant influences on the systemic exposure of galangin and its
      metabolites. (2) Galangin was preferentially glucuronidated after p.o. dosing but
      sulfated after i.v. medication. (3) Kaempferol conjugates were detected
      demonstrating that oxidation reaction occurred; however, both glucuronidation and
      sulfation were more efficient. (4) Oral bioavailability of free parent galangin
      was very low. CONCLUSIONS: Systemic exposure to galangin and its metabolites was
      different in rat plasma between oral and intravenous administration. Further
      research is needed to characterize the structures of galangin conjugates and to
      evaluate the biological activities of these metabolites. Graphical
      abstractGalangin was preferentially glucuronidated after p.o. dosing but sulfated
      after i.v. medication.

PMID- 25873995
TI  - Two years of gender identity service for minors: overrepresentation of natal
      girls with severe problems in adolescent development.
AB  - BACKGROUND: Increasing numbers of adolescents present in adolescent gender
      identity services, desiring sex reassignment (SR). The aim of this study is to
      describe the adolescent applicants for legal and medical sex reassignment during
      the first two years of adolescent gender identity team in Finland, in terms of
      sociodemographic, psychiatric and gender identity related factors and adolescent
      development. METHODS: Structured quantitative retrospective chart review and
      qualitative analysis of case files of all adolescent SR applicants who entered
      the assessment by the end of 2013. RESULTS: The number of referrals exceeded
      expectations in light of epidemiological knowledge. Natal girls were markedly
      overrepresented among applicants. Severe psychopathology preceding onset of
      gender dysphoria was common. Autism spectrum problems were very common.
      CONCLUSION: The findings do not fit the commonly accepted image of a gender
      dysphoric minor. Treatment guidelines need to consider gender dysphoria in minors
      in the context of severe psychopathology and developmental difficulties.

PMID- 25873996
TI  - Highly efficient enzymatic biodiesel production promoted by particle-induced
      emulsification.
AB  - BACKGROUND: At present, the conversion of oils to biodiesel is predominantly
      carried out using chemical catalysts. However, the corresponding lipase-catalysed
      process has important advantages, which include mild reaction conditions and the
      possibility of using cheap, low quality feedstocks with a high free fatty acid
      content. Further increases in the efficiency of the enzymatic process are desired
      to make it even more attractive and suitable for large-scale applications.
      RESULTS: Herein, we present a simple and efficient two-phase lipase-catalysed
      system for the preparation of biodiesel in which different parameters
      (biocatalyst composition, ethanol concentration and the presence of additives)
      were optimised in order to obtain the maximum productivity starting from triolein
      with a high free oleic acid content. In the two-phase system, the enzyme
      tolerated high-ethanol concentrations, which made it possible to reach high
      conversions. The addition of silica particles increased the reaction rate
      substantially. It was suggested that such particles can catalyse acyl migration
      as a step to the full conversion to glycerol and biodiesel. However, in the
      system studied here, the effect of the particles was shown to be due to the
      formation of smaller and more uniform emulsion droplets leading to better mass
      transfer between the two phases. Particles of widely different size had positive
      effects, and the highest rate was obtained with silica particles derivatised with
      phenyl groups. The optimal conditions were applied to the solvent-free
      ethanolysis of rapeseed oil, and a yield of 96% was reached in 5 h. Under the
      mild conditions used, chemical catalysts were inefficient. CONCLUSIONS:
      Triacylglycerol oils with a high free fatty acid content can be efficiently
      converted to ethyl esters using Thermomyces lanuginosus lipase as the catalyst in
      an aqueous/organic two-phase system. Fast mass transfer can be achieved using
      silica particles, which helped to decrease the size of the emulsion droplets and
      thus led to a more efficient process. The high-ethanol concentration tolerated by
      the lipase in this system made it possible to reach almost quantitative yields.

PMID- 25873997
TI  - Exploitation of algal-bacterial associations in a two-stage biohydrogen and
      biogas generation process.
AB  - BACKGROUND: The growing concern regarding the use of agricultural land for the
      production of biomass for food/feed or energy is dictating the search for
      alternative biomass sources. Photosynthetic microorganisms grown on marginal or
      deserted land present a promising alternative to the cultivation of energy plants
      and thereby may dampen the 'food or fuel' dispute. Microalgae offer diverse
      utilization routes. RESULTS: A two-stage energetic utilization, using a natural
      mixed population of algae (Chlamydomonas sp. and Scenedesmus sp.) and mutualistic
      bacteria (primarily Rhizobium sp.), was tested for coupled biohydrogen and biogas
      production. The microalgal-bacterial biomass generated hydrogen without sulfur
      deprivation. Algal hydrogen production in the mixed population started earlier
      but lasted for a shorter period relative to the benchmark approach. The residual
      biomass after hydrogen production was used for biogas generation and was compared
      with the biogas production from maize silage. The gas evolved from the microbial
      biomass was enriched in methane, but the specific gas production was lower than
      that of maize silage. Sustainable biogas production from the microbial biomass
      proceeded without noticeable difficulties in continuously stirred fed-batch
      laboratory-size reactors for an extended period of time. Co-fermentation of the
      microbial biomass and maize silage improved the biogas production: The
      metagenomic results indicated that pronounced changes took place in the domain
      Bacteria, primarily due to the introduction of a considerable bacterial biomass
      into the system with the substrate; this effect was partially compensated in the
      case of co-fermentation. The bacteria living in syntrophy with the algae
      apparently persisted in the anaerobic reactor and predominated in the bacterial
      population. The Archaea community remained virtually unaffected by the changes in
      the substrate biomass composition. CONCLUSION: Through elimination of cost- and
      labor-demanding sulfur deprivation, sustainable biohydrogen production can be
      carried out by using microalgae and their mutualistic bacterial partners. The
      beneficial effect of the mutualistic mixed bacteria in O2 quenching is that the
      spent algal-bacterial biomass can be further exploited for biogas production.
      Anaerobic fermentation of the microbial biomass depends on the composition of the
      biogas-producing microbial community. Co-fermentation of the mixed microbial
      biomass with maize silage improved the biogas productivity.

PMID- 25873998
TI  - Uniconazole-induced starch accumulation in the bioenergy crop duckweed (Landoltia
      punctata) II: transcriptome alterations of pathways involved in carbohydrate
      metabolism and endogenous hormone crosstalk.
AB  - BACKGROUND: Landoltia punctata is a widely distributed duckweed species with
      great potential to accumulate enormous amounts of starch for bioethanol
      production. We found that L. punctata can accumulate starch rapidly accompanied
      by alterations in endogenous hormone levels after uniconazole application, but
      the relationship between endogenous hormones and starch accumulation is still
      unclear. RESULTS: After spraying fronds with 800 mg/L uniconazole, L. punctata
      can accumulate starch quickly, with a dry weight starch content of up to 48%
      after 240 h of growth compared to 15.7% in the control group. Electron microscopy
      showed that the starch granule content was elevated after uniconazole
      application. The activities of key enzymes involved in starch synthesis were also
      significantly increased. Moreover, the expression of regulatory elements of the
      cytokinin (CK), abscisic acid (ABA) and gibberellin (GA) signaling pathways that
      are involved in chlorophyll and starch metabolism also changed correspondingly.
      Importantly, the expression levels of key enzymes involved in starch biosynthesis
      were up-regulated, while transcript-encoding enzymes involved in starch
      degradation and other carbohydrate metabolic branches were down-regulated.
      CONCLUSION: The increase of endogenous ABA and CK levels positively promoted the
      activity of ADP-glucose pyrophosphorylase (AGPase) and chlorophyll content, while
      the decrease in endogenous GA levels inactivated alpha-amylase. Thus, the
      alterations of endogenous hormone levels resulted in starch accumulation due to
      regulation of the expression of genes involved in the starch metabolism pathway.

PMID- 25873999
TI  - Integrated analysis reveals microRNA networks coordinately expressed with key
      proteins in breast cancer.
AB  - BACKGROUND: The role played by microRNAs in the deregulation of protein
      expression in breast cancer is only partly understood. To gain insight, the
      combined effect of microRNA and mRNA expression on protein expression was
      investigated in three independent data sets. METHODS: Protein expression was
      modeled as a multilinear function of powers of mRNA and microRNA expression. The
      model was first applied to mRNA and protein expression for 105 selected cancer
      associated genes and to genome-wide microRNA expression from 283 breast tumors.
      The model considered both the effect of one microRNA at a time and all microRNAs
      combined. In the latter case the Lasso penalized regression method was applied to
      detect the simultaneous effect of multiple microRNAs. RESULTS: An interactome map
      for breast cancer representing all direct and indirect associations between the
      expression of microRNAs and proteins was derived. A pattern of extensive
      coordination between microRNA and protein expression in breast cancer emerges,
      with multiple clusters of microRNAs being associated with multiple clusters of
      proteins. Results were subsequently validated in two independent breast cancer
      data sets. A number of the microRNA-protein associations were functionally
      validated in a breast cancer cell line. CONCLUSIONS: A comprehensive map is
      derived for the co-expression in breast cancer of microRNAs and 105 proteins with
      known roles in cancer, after filtering out the in-cis effect of mRNA expression.
      The analysis suggests that group action by several microRNAs to deregulate the
      expression of proteins is a common modus operandi in breast cancer.

PMID- 25874000
TI  - Ultradeep analysis of tumor heterogeneity in regions of somatic hypermutation.
AB  - Tumor heterogeneity is of growing importance in the treatment of cancers.
      Mutational hot spots are prime locations for determining number and proportions
      of low variant allele frequency (VAF) tumor subclones by next generation
      sequencing. Low VAF detection is complicated by poor mapping efficiency in
      regions with high mutation density. Our Deep-Drilling with iterative Mapping
      (DDiMAP) method retains variant allele patterns to aid in single nucleotide
      variation detection and generation of additional reference alleles, with
      remapping increasing coverage of highly mutated regions to capture data critical
      to heterogeneity analysis and enhancing sensitivity. DDiMAP outputs variant
      patterns with frequencies, enabling rapid phylogenetic analysis of ongoing
      mutation. 

PMID- 25874002
TI  - Multiplex Ligation-dependent Probe Amplification Can Clarify HER2 Status in
      Gastric Cancers with "Polysomy 17".
AB  - Therapy with trastuzumab confers a survival benefit in HER2 positive advanced
      gastric and gastroesophageal adenocarcinoma. HER2 status is evaluated by
      immunohistochemistry (IHC) and in situ hybridization (ISH). An ISH ratio of HER2
      to centromere 17 (CEP17) >=2.0 is considered amplified. This assumes that CEP17
      reflects chromosomal copy number. Cases where CEP17 exceeds 3 are classified as
      polysomic, but it's unknown if they represent true polysomy or centromeric
      amplification. This has implications on the validity of current ISH criteria.
      Multiplex ligation-dependent probe amplification (MLPA) allows simultaneous
      quantification of multiple loci and can distinguish between true polysomy and
      centromeric amplification. We selected 13 gastric cancers with CEP17 counts >=3.0
      (polyCEP17), and 8 non-polyCEP17 gastric cancer controls. Silver ISH for HER2 and
      CEP17 were performed and scored by manufacturer guidelines. We also performed an
      MLPA HER2 assay that evaluates 22 genes on chromosome 17. MLPA identified HER2
      amplification in 7 polyCEP17 cases compared to 2 identified by ISH. Overall, 9 of
      13 polyCEP17 cases had amplification of the peri-centromeric gene WSB1, compared
      to 1 of 8 non-polyCEP17 controls (p=0.02). This could account for ISH CEP17
      counts >=3.0. MLPA did not show any cases of complete chromosome 17 duplication
      and peri-centromeric amplification can explain most cases of ISH polyCEP17.
      Current ISH criteria may under-diagnose HER2 amplification in polyCEP17 cases due
      to flawed assumptions about polysomy. MLPA can detect HER2 amplification missed
      by IHC and ISH, and thus may be an effective ancillary technique in evaluating
      HER2 status. 

PMID- 25874001
TI  - A phase Ib multiple ascending dose study of the safety, tolerability, and central
      nervous system availability of AZD0530 (saracatinib) in Alzheimer's disease.
AB  - INTRODUCTION: Despite significant progress, a disease-modifying therapy for
      Alzheimer's disease (AD) has not yet been developed. Recent findings implicate
      soluble oligomeric amyloid beta as the most relevant protein conformation in AD
      pathogenesis. We recently described a signaling cascade whereby oligomeric
      amyloid beta binds to cellular prion protein on the neuronal cell surface,
      activating intracellular Fyn kinase to mediate synaptotoxicity. Fyn kinase has
      been implicated in AD pathophysiology both in in vitro models and in human
      subjects, and is a promising new therapeutic target for AD. Herein, we present a
      Phase Ib trial of the repurposed investigational drug AZD0530, a Src family
      kinase inhibitor specific for Fyn and Src kinase, for the treatment of patients
      with mild-to-moderate AD. METHODS: The study was a 4-week Phase Ib multiple
      ascending dose, randomized, double-blind, placebo-controlled trial of AZD0530 in
      AD patients with Mini-Mental State Examination (MMSE) scores ranging from 16 to
      26. A total of 24 subjects were recruited in three sequential groups, with each
      randomized to receive oral AZD0530 at doses of 50 mg, 100 mg, 125 mg, or placebo
      daily for 4 weeks. The drug:placebo ratio was 3:1. Primary endpoints were safety,
      tolerability, and cerebrospinal fluid (CSF) penetration of AZD0530. Secondary
      endpoints included changes in clinical efficacy measures (Alzheimer's Disease
      Assessment Scale - cognitive subscale, MMSE, Alzheimer's Disease Cooperative
      Study - Activities of Daily Living Inventory, Neuropsychiatric Inventory, and
      Clinical Dementia Rating Scale - Sum of Boxes) and regional cerebral glucose
      metabolism measured by fluorodeoxyglucose positron emission tomography. RESULTS:
      AZD0530 was generally safe and well tolerated across doses. One subject receiving
      125 mg of AZD0530 was discontinued from the study due to the development of
      congestive heart failure and atypical pneumonia, which were considered possibly
      related to the study drug. Plasma/CSF ratio of AZD0530 was 0.4. The 100 mg and
      125 mg doses achieved CSF drug levels corresponding to brain levels that rescued
      memory deficits in transgenic mouse models. One-month treatment with AZD0530 had
      no significant effect on clinical efficacy measures or regional cerebral glucose
      metabolism. CONCLUSIONS: AZD0530 is reasonably safe and well tolerated in
      patients with mild-to-moderate AD, achieving substantial central nervous system
      penetration with oral dosing at 100-125 mg. Targeting Fyn kinase may be a
      promising therapeutic approach in AD, and a larger Phase IIa clinical trial of
      AZD0530 for the treatment of patients with AD has recently launched. TRIAL
      REGISTRATION: ClinicalTrials.gov: NCT01864655. Registered 12 June 2014.

PMID- 25874003
TI  - Synonymous Polymorphisms in HOXB13 as a Protective Factor for Prostate Cancer.
AB  - BACKGROUND: Genomic association and linkage studies, as well as epidemiological
      data have implicated both the HOXB13 gene and single nucleotide polymorphisms
      (SNPs) in the development of prostate cancer (PCa). The recent association
      between the G84E polymorphism in the HOXB13 gene and PCa has been shown to result
      in a more aggressive cancer with an earlier onset of the disease. We examined the
      frequency of this mutation and other recurrent HOXB13 SNPs in patients with PCa
      and those with benign prostatic hyperplasia (BPH) or no cancer. METHODS: Reverse
      transcriptase-polymerase chain reaction (RT-PCR) was performed on exons 1 and 2
      of HOXB13 gene, followed by bidirectional Sanger Sequencing on peripheral blood
      from 232 PCa (age 46-92) and 110 BPH (age 45-84) patients. Statistical analysis
      was used to correlate between recurrent SNPs and PCa. RESULTS: The G84E mutation
      was found at a low frequency in randomly selected PCa and BPH (both 0.9%). Two
      recurrent, synonymous SNPs, rs8556 and rs900627, were also detected. rs8556 was
      detected in 48 PCa (20.7%) and 26 BPH (23.6%) subjects; rs9900627was detected in
      27 PCa (11.6%) and 19 BPH (17.3%) subjects. Having both rs8556 and rs9900627 or
      being homozygous for either one was associated with being 2.9 times less likely
      to develop PCa (p=0.05). CONCLUSIONS: Although a larger study in order to confirm
      our findings, our data suggests a significant negative correlation between two
      SNPs, rs8556 and rs9900627, and the presence of PCa.

PMID- 25874004
TI  - Prognostic significance of lymphovascular space invasion in epithelial ovarian
      cancer.
AB  - OBJECT: To assess the effects of lymphovascular space invasion (LVSI) on cancer
      recurrence and survival in patients with primary epithelial ovarian cancer.
      METHODS: A retrospective study was conducted of patients with stage I-IV primary
      epithelial ovarian cancer who underwent cytoreductive surgery. LVSI is defined as
      the presence of tumor cells within an endothelium-lined space, and the patients'
      pathologic slides were reevaluated by gynecological pathologists. Survival
      analysis was performed to compare risk factors. RESULTS: A total of 492 patients
      were included in the analysis. The incidence of LVSI was 58.5% in our cohort (288
      cases), and it was significantly associated with advanced stage, high-grade
      serous histology, high grade, and lymph node metastasis (P<0.001). Kaplan-Meier
      analysis demonstrated that LVSI was only correlated with decreased PFS (5-year
      rate, 39% vs. 66%, P<0.001) and OS (5-year rate, 44% vs. 78%, P<0.001) in
      patients at early stage but not at advanced stage (5-year rate, PFS: 14% vs. 11%,
      P<0.001; OS: 29% vs. 29%, P=0.141). Multivariate analysis showed that LVSI
      remained a significant variable with PFS and OS in early-stage ovarian cancer
      (PFS: HR 2.29, 95% CI 1.45-3.57; OS: HR 2.20, 95% CI 1.59-3.44, both P<0.001).
      CONCLUSION: LVSI is an independent predictor of progression and survival in
      patients with primary epithelial ovarian cancer at early stage but not at
      advanced stage.

PMID- 25874005
TI  - Increased Expression of GOLPH3 is Associated with the Proliferation of Prostate
      Cancer.
AB  - BACKGROUND: Golgi phosphoprotein 3 (GOLPH3) is a metastasis-associated gene,
      however its role in cell proliferation of prostate cancer (PCa) has not yet been
      elucidated. METHODS: The level of expression of GOLPH3 and other genes was
      examined by quantitative real-time PCR (QPCR) and western blot analysis.
      Furthermore, we performed a comprehensive analysis of the expression of GOLPH3 in
      PCa using a tissue microarray (TMA) and correlated our findings with pathological
      parameters of PCa. RNA interference (RNAi) was used to silence the expression of
      GOLPH3 in PC-3 cells and to measure the effects on proliferation and cell cycle
      using the CCK-8 assay and flow cytometry. Western blots were also employed to
      assess AKT-mTOR and cell cycle-related proteins. RESULTS: We showed that the
      expression of GOLPH3 was located at the trans-Golgi membranes in PCa cells. We
      found that GOLPH3 was expressed in all PCa cells and was significantly higher in
      two androgen-independent cell lines, DU145 and PC-3. TMA immunohistochemistry
      showed that GOLPH3 was positive in 64% of cancer tissue samples compared with 20%
      in normal and 30% in benign samples (P<0.05). In vitro, silencing GOLPH3
      expression inhibited cell proliferation and arrested the cell cycle at the G2/M
      phase. Silencing GOLPH3 also activated P21 expression but suppressed the
      expression of CDK1/2 and cyclinB1 protein together with the phosphorylation of
      AKT and mTOR. CONCLUSIONS: The expression of the GOLPH3 protein was significantly
      elevated in PCa. GOLPH3 can promote cell proliferation by enhancing the activity
      of AKT-mTOR signaling. Altogether, these findings suggest that GOLPH3 play
      important roles in proliferation and cell cycle regulation in PCa and might serve
      as promising biomarkers for PCa progression as well as potential therapeutic
      targets.

PMID- 25874006
TI  - Effects of Hypoxia, Surrounding Fibroblasts, and p16 Expression on Breast Cancer
      Cell Migration and Invasion.
AB  - Cancer cell migration and invasion play essential roles in the metastatic cascade
      that transforms the local, noninvasive confined tumor cells to the motile,
      metastatic cancer cells moving through the extracellular matrix and basement into
      the circulation. Accumulated evidences suggest that intratumoral hypoxia, a
      characteristic of fast-growing solid tumors, promotes cancer cell motile and
      invasive abilities. In this study, we investigated the effects of hypoxia,
      surrounding fibroblasts, and p16 expression on the migration and invasion of
      breast cancer cells. We found that hypoxia promoted breast cancer cell migration
      and invasion, and cocultured fibroblasts stimulated invasiveness of breast cancer
      cells. Moreover, by using a Tet-on inducible system, we found that p16 is capable
      of inhibiting hypoxia-induced cell migration and invasion of breast cancer cells,
      and suppressing cocultured fibroblast-stimulated invasiveness of breast cancer
      cells. These results suggest that p16, in addition to its well-known anti-tumor
      proliferation function, has novel anti-cancer properties capable of suppressing
      hypoxia-mediated cancer cell migration and invasion. This study may provide
      important validation for p16-mediated cancer therapy either by gene therapy or
      pharmacological activation of internal p16 gene that is usually inactive due to
      hypermethylation in the tumor cells. 

PMID- 25874007
TI  - Problems of Long Survival Following Surgery in Patients with NonBNonC-HCC:
      Comparison with HBV and HCV Related-HCC.
AB  - BACKGROUND: The number of patients with hepatocellular carcinoma (HCC) in the
      absence of both hepatitis B virus surface antigen (HBsAg) and hepatitis C virus
      antibody (HCVAb) (NBNC-HCC) has been rapidly increasing in Japan. The objective
      of this study was to compare the clinical and pathological characteristics
      between patients with the NBNC-HCC, those with HBsAg positive HCC (B-related HCC)
      and HCVAb positive HCC (C-related HCC). A better understanding will facilitate
      the development of postoperative strategies to better manage patients with NBNC
      HCC. METHODS: Consecutive 219 patients with primary HCC: (B-related, n=35; C
      related, n = 104; NBNC, n = 80) were treated by hepatic resection or ablation.
      Clinicopathological characteristics including postoperative course were
      retrospectively compared between the three groups. RESULTS: When comparing within
      stage I and II, the NBNC-HCC group had improved recurrence free survival (RFS)
      compared to the C-related HCC (p = 0.013) but had not been good overall survival
      (OS). Moreover, the NBNC-HCC group showed higher rate of death due to other
      cancers and cardiovascular disease (p = 0.011) compared to the C-related HCC.
      Multivariate analysis revealed that the only prognostic factor for RFS in the
      NBNC-HCC group was high serum total bilirubin. CONCLUSIONS: In the patients with
      the NBNC-HCC, elevated serum bilirubin could predict poor RFS after surgery.
      Furthermore, patients must be carefully followed-up not only for HCC but also for
      the occurrence of other critical diseases including multiple other cancers.

PMID- 25874008
TI  - Anti-Gastrins Antiserum Combined with Lowered Dosage Cytotoxic Drugs to Inhibit
      the Growth of Human Gastric Cancer SGC7901 Cells in Nude Mice.
AB  - The objective of this study was to determine the effect of anti-gastrin antiserum
      in combination with varied dosages of cytotoxic drugs (5-Fluorouracil (5FU) +
      Cisplatin (CDDP)) in vivo growth of the human gastric cancer cell-line, SGC-7901,
      which expressed cholecystokininB/gastrin receptors and secreted gastrin. The anti
      gastrin antiserum was obtained by immunizing rabbits using a novel immunogen
      vaccine, which was composed of the common amino-terminal portion of human carboxy
      amidated gastrin-17 (G17) and glycine-extended gastrin-17 (gly-G17) and the
      common carboxy-terminal portion of progastrin (in a 50:50 mixture) all covalently
      linked to tetanus toxoid (TT) by specific peptide spacers. The antiserum
      neutralized both G17 and gly-G17 by enzyme-linked immunosorbent assay (ELISA),
      and a synthetic progastrin peptide, as well, using an E. coli expressed his
      tagged progastrin. The tumor was implanted subcutaneously into the backside of
      BALB/c nude mice, and the combination antibody-drug treatment using low dose
      combination chemotherapy had significantly reduced median tumor volumes (62%
      reduction; p =0.0018) and tumor weights (53% reduction; p =0.0062) when compared
      to the conventional high dose chemotherapy treated control mice that had a
      corresponding similar reductive effect, using just the two standard cytotoxic
      drugs alone; namely by reducing the tumor volumes (65%; p =0.0016) and tumor
      weights (59% reduction; p=0.0033). Importantly, the immunological treatment had
      little of the toxicities and side-effects of the full chemotherapy doses alone,
      which was effected by using a significant decrease in the dosage of
      chemotherapeutic drugs, while maintaining the same level of efficacy at reduction
      of tumor growth. 

PMID- 25874009
TI  - Hypotheses of cancer weakening and origin.
AB  - Approximately 2.7 billion years ago, cyanobacteria began producing oxygen by
      photosynthesis. Any free oxygen they produced was chemically captured by
      dissolved iron or organic matter. There was no ozone layer to protect living
      species against the radiation from space. Eukaryotic cells lived in water, under
      hypoxic environments, and metabolized glucose by fermentation. The Great
      Oxygenation Event (GOE) describes the point when oxygen sinks became saturated.
      This massive oxygenation of the Earth occurred approximately half a billion years
      ago. Species that evolved after the GOE are characterized by aerobic metabolism.
      Mammals evolved approximately a few hundred million years ago, with the ancient
      eukaryotic genes deeply embedded in their genome. Many genes have been exchanged
      by horizontal gene transfer (HGT) throughout the history of cellular evolution.
      Mammals have been invaded by viruses, and while viral genetic relics are embedded
      in mammalian junk genes, not all junk genes are genetic relics of viruses. These
      viral relics have been inactivated through evolution and have little impact on
      mammalian life. However, there is evidence to suggest that these viral genetic
      relics are linked to cancer. This hypothesis states that cancer develops when
      cell reproduction becomes defective because of the active involvement of viral
      genes, in a process similar to genetic engineering. Cancer cells are
      amalgamations of genetically modified organisms (GMOs). There are two main groups
      in cancer development. One group of cells arises by genetic engineering of a
      viral genetic relic, such as endogenous retroviruses (ERVs), which evolved after
      oxygenation of the atmosphere. This group is referred to here as genetically
      modified organisms from viral genes (GMOV). GMOVs may be inhibited by anticancer
      drugs. The second group arises by engineering of the genes of ancient eukaryotes,
      which existed prior to the oxygenation of the Earth. This second group is
      referred to as genetically modified organisms from ancient eukaryotic genes
      (GMOE). The GMOE group lives in hypoxic environments and metabolizes glucose by
      fermentation. GMOEs represent advanced cancer, which proliferate aggressively and
      are resistant to DNA damage. It has been demonstrated that as an ERV becomes more
      prevalent in a mammalian genome, the possibility that the mammal will develop
      cancer increases. The hypothesis also states that most cancers have their origins
      in GMOV by the incorporation of viral genes from junk genes. As the cancer
      progresses, further subgroups of cancer GMOs will develop. If the cancer advances
      even further, the GMOE could eventually develop prior to late-stage cancer.
      Because the genes of ancient eukaryotes have enhanced innate immunity, GMOE will
      eventually prevail over the weaker GMOV during cancer subgroup competition.
      Hence, cancer development is mainly determined by genes in the mammalian genome.
      An inherent weakness of cancer cells is their dependence on glucose and iron.
      Furthermore, they cannot tolerate physical disturbance. Ancient gene GMOs can be
      treated with a combination of mechanical vibration using glucose-coated magnetic
      nanoparticles and strengthening of the immune system. Herein, I suggest trials
      for verifying this hypothesis. 

PMID- 25874010
TI  - Risk factors for discontinuation of s-1 adjuvant chemotherapy for gastric cancer.
AB  - PURPOSE: The aim of this study was to clarify the risk factors for discontinuing
      tegafur/gimeracil/oteracil potassium (S-1) adjuvant chemotherapy following
      gastrectomy in patients with gastric cancer. METHODS: We retrospectively
      investigated patients with curatively-resected gastric cancer who received S-1
      adjuvant chemotherapy. S-1 was administered orally at 80-120 mg/day, depending on
      body surface area, on days 1-28 every 6 weeks for 1 year. The dose and treatment
      schedule were modified at the clinicians' discretion, according to toxicity.
      RESULTS: Seventy-one patients were included in the study, 26 of whom discontinued
      S-1 therapy. The relapse-free survival rates in the S-1-completed and S-1
      discontinuation groups at 5 years post-surgery were 88.1% and 55.8%,
      respectively. The overall survival rates in the S-1-completed and S-1
      discontinuation groups at 5 years post-surgery were 89.4% and 59.8%,
      respectively. The hazard ratios for relapse and death were significantly lower in
      the S-1-completed group compared with those in the S-1-discontinuation group
      (0.18; p<0.001 and 0.19; p=0.002, respectively). Multivariate logistic regression
      analysis revealed that S-1 discontinuation was significantly associated with an
      initial overdose of S-1, having stage I cancer, creatinine clearance <66 mL/min,
      and a side effect of nausea. CONCLUSIONS: These results suggest that assessing
      renal function to avoid initial overdose of S-1, together with the early
      management of side effects, may support the continuation of S-1 adjuvant
      chemotherapy in patients with gastric cancer.

PMID- 25874011
TI  - Role of mitochondrial network stabilisation by a human small heat shock protein
      in tumour malignancy.
AB  - Previously, we found that the unconventional small human heat-shock protein
      HSPB11 inhibits cell death by HSP90 mediated cholesterol-rich membrane
      microdomain dependent activation of phosphatidylinositol-3 kinase/protein kinase
      B pathway and by stabilising the mitochondrial membrane systems. Also,
      progressive cytoplasmic expression of HSPB11 correlated with brain tumor
      malignancy. In the present study we investigated how cytoplasmic abundance of
      HSPB11 augments tumor malignancy. We up- and downregulated the cytoplasmic level
      of HSPB11 before paclitaxel exposure in NIH3T3 and HeLa cells, which normally
      express low and high levels, respectively, of the HSPB11 protein. We examined the
      paclitaxel-mediated induction of cell death, mitochondrial fission, HSPB11
      mitochondrial translocation and inhibitory phosphorylation of dynamin-like
      protein-1 (DLP1). We found that increasing cytoplasmic abundance of HSPB11 in
      NIH3T3 cells protected against paclitaxel-induced apoptosis, while suppressing
      HSPB11 in HeLa cells sensitised the cells toward paclitaxel. Also, paclitaxel
      enhanced mitochondrial translocation of HSPB11 in wild type HeLa but not in
      NIH3T3 cells. More importantly, increased cytoplasmic level of HSPB11 in NIH3T3
      cells enhanced the inhibitory phosphorylation of DLP1 and attenuated paclitaxel
      induced mitochondrial fission. All these results suggest that increased
      cytoplasmic abundance of HSPB11 augments inhibitory phosphorylation of DLP1
      thereby reduces mitochondrial fission that eventually leads to decreased
      apoptosis. This novel mechanism may explain the resistance to apoptosis and
      increased malignancy of HSPB11-overexpressing tumours. The clinical significance
      of this mechanism has already been highlighted by the finding that the kinase
      inhibitor tyrphostin A9 induces cancer cell death by DLP1-mediated mitochondrial
      fragmentation. 

PMID- 25874012
TI  - Association of BTBD7 with Metastasis and Poor Prognosis in Non-Small-Cell Lung
      Cancer Patients.
AB  - Metastasis in lung cancer portends a poor prognosis, and the epithelial
      mesenchymal transition (EMT) in lung cancer cells is considered a prerequisite to
      achieve metastatic potential. Recent studies indicate that BTB/POZ domain
      containing protein 7 (BTBD7) regulates EMT-associated proteins in human
      malignancies and however, the role of BTBD7 in lung cancer have not been
      identified. In present study, we examined BTBD7 expression status and its
      association with unfavorable clinical features in non-small-cell lung cancer
      (NSCLC). Firstly, we studied the fresh specimens, and found that both mRNA and
      protein expression levels of BTBD7 in NSCLC tissue were significantly increased
      compared with the adjacent nontumorous lung tissue. Then, we determined BTBD7
      protein expressions in the paraffin-embedded samples from NSCLC patients, and
      analyzed the relations of BTBD7 expression with clinicopathologic features of the
      patients. The results showed that incidence of metastasis in patients with
      positive BTBD7 expression was significantly higher than that in those with
      negative BTBD7 expression, and the positive BTBD7 expression rate in metastatic
      cases was significantly higher than that in non-metastatic ones; furthermore, Cox
      regression analyses revealed that BTBD7 was an independent risk factor for either
      metastasis or survival in NSCLC patients. Thus, we conclude that BTBD7
      contributes to metastasis of NSCLC and BTBD7-positive NSCLC may have a high
      potential for metastasis and thereby a poor prognosis. 

PMID- 25874013
TI  - Hyponatremia in hepatocellular carcinoma complicating with cirrhosis.
AB  - BACKGROUND AND AIMS: We aimed to investigate the effect of serum sodium level on
      survival in hepatocellular carcinoma (HCC) patients complicating with liver
      cirrhosis (LC). METHODS: A total of 1170 HCC patients with LC were analysed. We
      classified these patients into three groups according to serum sodium level at
      HCC diagnosis: group A (n=96); serum sodium <=135 mmol/L, group B (n=520); 135
      mmol/L < serum sodium <=140 mmol/L, group C (n=554); serum sodium >140 mmol/L. We
      compared the baseline characteristics and overall survival (OS) among these three
      groups. Furthermore, we examined the factors linked to OS using univariate and
      multivariate analyses. RESULTS: In our results, decreased baseline serum sodium
      level was significantly associated with Child-Pugh classification and HCC stage
      along with several laboratory parameters in groups A, B and C. The median follow
      up period was 1.1 years in group A, 2.4 years in group B and 3.3 years in group
      C. The 1-, 3- and 5-year cumulative OS rates in groups A, B and C were 64.8%,
      46.9% and 25.7%, respectively, in group A, 85.5%, 60.5% and 41.1%, respectively,
      in group B and 90.7%, 66.6% and 48.2%, respectively, in group C (P<0.001). The
      multivariate analyses showed that Child-Pugh classification (P<0.001), HCC stage
      (P<0.001), serum sodium (P<0.001), aspartate aminotransferase >=57 IU/L
      (P=0.002), alkaline phosphatase >=348 IU/L (P<0.001), alpha-fetoprotein >=29.2
      ng/mL (P=0.019) and des-gamma-carboxy prothrombin >=55 mAU/mL (P<0.001) were
      significant independent predictors linked to OS. CONCLUSION: Lower serum sodium
      concentration is a useful predictor in HCC patients complicating with LC.

PMID- 25874014
TI  - Genetic Variability of MicroRNA Genes in 15 Animal Species.
AB  - MicroRNAs (miRNA) are a class of non-coding RNAs important in posttranscriptional
      regulation of target genes. Previous studies have proven that genetic variability
      of miRNA genes (miR-SNP) has an impact on phenotypic variation and disease
      susceptibility in human, mice and some livestock species. MicroRNA gene
      polymorphisms could therefore represent biomarkers for phenotypic traits also in
      other animal species. We upgraded our previously developed tool miRNA SNiPer to
      the version 4.0 which enables the search of miRNA genetic variability in 15
      animal genomes: http://www.integratomics-time.com/miRNA-SNiPer. Genome-wide in
      silico screening (GWISS) of 15 genomes revealed that based on the current
      database releases, miRNA genes are most polymorphic in cattle, followed by human,
      fruitfly, mouse, chicken, pig, horse, and sheep. The difference in the number of
      miRNA gene polymorphisms between species is most probably not due to a biological
      reason and lack of genetic variability in some species, but to different stage of
      sequencing projects and differences in development of genomic resource databases
      in different species. Genome screening revealed several interesting genomic
      hotspots. For instance, several multiple nucleotide polymorphisms (MNPs) are
      present within mature seed region in cattle. Among miR-SNPs 46 are present on
      commercial whole-genome SNP chips: 16 in cattle, 26 in chicken, two in sheep and
      two in pig. The update of the miRNA SNiPer tool and the generated catalogs will
      serve researchers as a starting point in designing projects dealing with the
      effects of genetic variability of miRNA genes. 

PMID- 25874015
TI  - Draft Genome Sequence of Multidrug Resistant Salmonella enterica serovar
      Weltevreden Isolated from Seafood.
AB  - Salmonella enterica subsp. enterica serovar Weltevereden is the most frequent
      serovar isolated from Asia. Here, we report a draft genome sequence of multidrug
      resistant Salmonella Weltevreden 9 isolated from seafood. Whole-genome of this
      isolate and annotation will help enhance the understanding of this pathogenic
      multidrug-resistant serovar. 

PMID- 25874016
TI  - Map-based comparative genomic analysis of virulent haemophilus parasuis serovars
      4 and 5.
AB  - Haemophilus parasuis is a commensal bacterium of the upper respiratory tract of
      healthy pigs. However, in conjunction with viral infections in immunocompromised
      animals H. parasuis can transform into a pathogen that is responsible for causing
      Glasser's disease which is typically characterized by fibrinous polyserositis,
      polyarthritis, meningitis and sometimes acute pneumonia and septicemia in pigs.
      Haemophilus parasuis serovar 5 is highly virulent and more frequently isolated
      from respiratory and systemic infection in pigs. Recently a highly virulent H.
      parasuis serovar 4 was isolated from the tissues of diseased pigs. To understand
      the differences in virulence and virulence-associated genes between H. parasuis
      serovar 5 and highly virulent H. parasuis serovar 4 strains, a genomic library
      was generated by TruSeq preparation and sequenced on Illumina HiSeq 2000
      obtaining 50 bp PE reads. A three-way comparative genomic analysis was conducted
      between two highly virulent H. parasuis serovar 4 strains and H. parasuis serovar
      5. Haemophilus parasuis serovar 5 GenBank isolate SH0165 (GenBank accession
      number CP001321.1) was used as reference strain for assembly. Results of these
      analysis revealed the highly virulent H. parasuis serovar 4 lacks genes encoding
      for, glycosyl transferases, polysaccharide biosynthesis protein capD, spore coat
      polysaccharide biosynthesis protein C, polysaccharide export protein and
      sialyltransferase which can modify the lipopolysaccharide forming a short-chain
      LPS lacking O-specific polysaccharide chains often referred to as
      lipooligosaccharide (LOS). In addition, it can modify the outer membrane protein
      (OMP) structure. The lack of sialyltransferase significantly reduced the amount
      of sialic acid incorporated into LOS, a major and essential component of the cell
      wall and an important virulence determinant. These molecules may be involved in
      various stages of pathogenesis through molecular mimicry and by causing host cell
      cytotoxicity, reduced inflammatory and immunological response to infection with
      this organism. The mechanism by which sialyation of LPS contributes to virulence
      is a key to understanding the pathogenesis of this highly virulent H. parasuis
      serovar 4. This analysis also revealed the presence of virulence associated genes
      similar to the MerR family transcriptional regulators, macrophage infectivity
      potentiator protein, hemolysin, opacity associated protein, toxin antitoxin
      system, and virulence associated protein D and colicins. Haemophilus parasuis
      serovar 4 variants also possess extensive metal ion uptake and regulation
      mechanism which controls various virulence and virulence associated genes. A
      combination of virulence associated factors and/or genes and proteins with
      overlapping functions may be responsible for the apparent enhanced virulence of
      this organism. The extensive structural modification of LOS and OMP of variant H.
      parasuis serovar 4 strains appear to aid in nasal colonization, are associated
      with the organisms' ability to evade the host immune response and provide serum
      resistance. In addition, the combination of capsule modification and phase
      variation due to LOS substitutions could help variant H. parasuis serovar 4
      transform into a highly virulent pathogen. Based on these results, the variant H.
      parasuis serovar 4 strains harbor a diverse repertoire of virulence associated
      genes which have not been previously reported. 

PMID- 25874017
TI  - Age-associated DNA methylation changes in immune genes, histone modifiers and
      chromatin remodeling factors within 5 years after birth in human blood
      leukocytes.
AB  - BACKGROUND: Age-related changes in DNA methylation occurring in blood leukocytes
      during early childhood may reflect epigenetic maturation. We hypothesized that
      some of these changes involve gene networks of critical relevance in leukocyte
      biology and conducted a prospective study to elucidate the dynamics of DNA
      methylation. Serial blood samples were collected at 3, 6, 12, 24, 36, 48 and 60
      months after birth in ten healthy girls born in Finland and participating in the
      Type 1 Diabetes Prediction and Prevention Study. DNA methylation was measured
      using the HumanMethylation450 BeadChip. RESULTS: After filtering for the presence
      of polymorphisms and cell-lineage-specific signatures, 794 CpG sites showed
      significant DNA methylation differences as a function of age in all children
      (41.6% age-methylated and 58.4% age-demethylated, Bonferroni-corrected P value
      <0.01). Age-methylated CpGs were more frequently located in gene bodies and
      within +5 to +50 kilobases (kb) of transcription start sites (TSS) and enriched
      in developmental, neuronal and plasma membrane genes. Age-demethylated CpGs were
      associated to promoters and DNAse-I hypersensitivity sites, located within -5 to
      +5 kb of the nearest TSS and enriched in genes related to immunity, antigen
      presentation, the polycomb-group protein complex and cytoplasm. CONCLUSIONS: This
      study reveals that susceptibility loci for complex inflammatory diseases (for
      example, IRF5, NOD2, and PTGER4) and genes encoding histone modifiers and
      chromatin remodeling factors (for example, HDAC4, KDM2A, KDM2B, JARID2, ARID3A,
      and SMARCD3) undergo DNA methylation changes in leukocytes during early
      childhood. These results open new perspectives to understand leukocyte maturation
      and provide a catalogue of CpG sites that may need to be corrected for age
      effects when performing DNA methylation studies in children.

PMID- 25874018
TI  - Interest in genomic SNP testing for prostate cancer risk: a pilot survey.
AB  - BACKGROUND: Advancements in genomic testing have led to the identification of
      single nucleotide polymorphisms (SNPs) associated with prostate cancer. The
      clinical utility of SNP tests to evaluate prostate cancer risk is unclear.
      Studies have not examined predictors of interest in novel genomic SNP tests for
      prostate cancer risk in a diverse population. METHODS: Consecutive participants
      in the Fox Chase Prostate Cancer Risk Assessment Program (PRAP) (n = 40) and
      unselected men from surgical urology clinics (n = 40) completed a one-time
      survey. Items examined interest in genomic SNP testing for prostate cancer risk,
      knowledge, impact of unsolicited findings, and psychosocial factors including
      health literacy. RESULTS: Knowledge of genomic SNP tests was low in both groups,
      but interest was higher among PRAP men (p < 0.001). The prospect of receiving
      unsolicited results about ancestral genomic markers increased interest in testing
      in both groups. Multivariable modeling identified several predictors of higher
      interest in a genomic SNP test including higher perceived risk (p = 0.025),
      indicating zero reasons for not wanting testing (vs >=1 reason) (p = 0.013), and
      higher health literacy (p = 0.016). CONCLUSIONS: Knowledge of genomic SNP testing
      was low in this sample, but higher among high-risk men. High-risk status may
      increase interest in novel genomic tests, while low literacy may lessen interest.

PMID- 25874019
TI  - Assessment of eccentric exercise-induced oxidative stress using oxidation
      reduction potential markers.
AB  - The aim of the present study was to investigate the use of static (sORP) and
      capacity ORP (cORP) oxidation-reduction potential markers as measured by the
      RedoxSYS Diagnostic System in plasma, for assessing eccentric exercise-induced
      oxidative stress. Nineteen volunteers performed eccentric exercise with the knee
      extensors. Blood was collected before, immediately after exercise, and 24, 48,
      and 72 h after exercise. Moreover, common redox biomarkers were measured, which
      were protein carbonyls, thiobarbituric acid-reactive substances, total
      antioxidant capacity in plasma, and catalase activity and glutathione levels in
      erythrocytes. When the participants were examined as one group, there were not
      significant differences in any marker after exercise. However, in 11 participants
      there was a high increase in cORP after exercise, while in 8 participants there
      was a high decrease. Thus, the participants were divided in low cORP group
      exhibiting significant decrease in cORP after exercise and in high cORP group
      exhibiting significant increase. Moreover, only in the low cORP group there was a
      significant increase in lipid peroxidation after exercise suggesting induction of
      oxidative stress. The results suggested that high decreases in cORP values after
      exercise may indicate induction of oxidative stress by eccentric exercise, while
      high increases in cORP values after exercise may indicate no existence of
      oxidative stress.

PMID- 25874020
TI  - Acute exercise induced mitochondrial H2O2 production in mouse skeletal muscle:
      association with p(66Shc) and FOXO3a signaling and antioxidant enzymes.
AB  - Exercise induced skeletal muscle phenotype change involves a complex interplay
      between signaling pathways and downstream regulators. This study aims to
      investigate the effect of acute exercise on mitochondrial H2O2 production and its
      association with p(66Shc), FOXO3a, and antioxidant enzymes. Male ICR/CD-1 mice
      were subjected to an acute exercise. Muscle tissues (gastrocnemius and quadriceps
      femoris) were taken after exercise to measure mitochondrial H2O2 content,
      expression of p(66Shc) and FOXO3a, and the activity of antioxidant enzymes. The
      results showed that acute exercise significantly increased mitochondrial H2O2
      content and expressions of p(66Shc) and FOXO3a in a time-dependent manner, with a
      linear correlation between the increase in H2O2 content and p(66Shc) or FOXO3a
      expression. The activity of mitochondrial catalase was slightly reduced in the 90
      min exercise group, but it was significantly higher in groups with 120 and 150
      min exercise compared to that of 90 min exercise group. The activity of SOD was
      not significantly affected. The results indicate that acute exercise increases
      mitochondrial H2O2 production in the skeletal muscle, which is associated with
      the upregulation of p(66Shc) and FOXO3a. The association of p(66Shc) and FOXO3a
      signaling with exercise induced H2O2 generation may play a role in regulating
      cellular oxidative stress during acute exercise. 

PMID- 25874021
TI  - Dietary supplementation with the microalga Galdieria sulphuraria (Rhodophyta)
      reduces prolonged exercise-induced oxidative stress in rat tissues.
AB  - We studied the effects of ten-day 1% Galdieria sulphuraria dietary
      supplementation on oxidative damage and metabolic changes elicited by acute
      exercise (6-hour swimming) determining oxygen consumption, lipid hydroperoxides,
      protein bound carbonyls in rat tissue (liver, heart, and muscle) homogenates and
      mitochondria, tissue glutathione peroxidase and glutathione reductase activities,
      glutathione content, and rates of H2O2 mitochondrial release. Exercise increased
      oxidative damage in tissues and mitochondria and decreased tissue content of
      reduced glutathione. Moreover, it increased State 4 and decreased State 3
      respiration in tissues and mitochondria. G. sulphuraria supplementation reduced
      the above exercise-induced variations. Conversely, alga supplementation was not
      able to modify the exercise-induced increase in mitochondrial release rate of
      hydrogen peroxide and in liver and heart antioxidant enzyme activities. The alga
      capacity to reduce lipid oxidative damage without reducing mitochondrial H2O2
      release can be due to its high content of C-phycocyanin and glutathione, which
      are able to scavenge peroxyl radicals and contribute to phospholipid
      hydroperoxide metabolism, respectively. In conclusion, G. sulphuraria ability to
      reduce exercise-linked oxidative damage and mitochondrial dysfunction makes it
      potentially useful even in other conditions leading to oxidative stress,
      including hyperthyroidism, chronic inflammation, and ischemia/reperfusion. 

PMID- 25874022
TI  - Exercise training and calorie restriction influence the metabolic parameters in
      ovariectomized female rats.
AB  - The estrogen deficiency after menopause leads to overweight or obesity, and
      physical exercise is one of the important modulators of this body weight gain.
      Female Wistar rats underwent ovariectomy surgery (OVX) or sham operation (SO).
      OVX and SO groups were randomized into new groups based on the voluntary physical
      activity (with or without running) and the type of diet for 12 weeks. Rats were
      fed standard chow (CTRL), high triglyceride diet (HT), or restricted diet (CR).
      The metabolic syndrome was assessed by measuring the body weight gain, the
      glucose sensitivity, and the levels of insulin, triglyceride, leptin, and
      aspartate aminotransferase transaminase (AST) and alanine aminotransferase (ALT).
      The exercise training combined with the CR resulted in improvements in the
      glucose tolerance and the insulin sensitivity. Plasma TG, AST, and ALT levels
      were significantly higher in OVX rats fed with HT but these high values were
      suppressed by exercise and CR. Compared to SO animals, estrogen deprivation with
      HT caused a significant increase in leptin level. Our data provide evidence that
      CR combined with voluntary physical exercise can be a very effective strategy to
      prevent the development of a metabolic syndrome induced by high calorie diet. 

PMID- 25874023
TI  - Relationship between inflammation and oxidative stress and cognitive decline in
      the institutionalized elderly.
AB  - OBJECTIVE: Cognitive impairment reduces quality of life and is related to
      vascular and neurodegenerative disorders. However, there is also a close
      relationship between these diseases and oxidative stress. Thus, the purpose of
      this study was to assess whether inflammation and oxidative damage are associated
      with low cognitive performance in the elderly with different housing conditions.
      METHODS: The study groups consisted of 32 institutionalized and 25
      noninstitutionalized Brazilian elderly subjects. Oxidative damage, inflammation
      markers, and cognitive function were evaluated. RESULTS: The results demonstrated
      pronounced oxidative stress in the institutionalized elderly group, which also
      had a lower antioxidant status compared to noninstitutionalized subjects. High
      levels of proinflammatory cytokines were also observed in the institutionalized
      elderly. Furthermore, the raised levels of inflammatory markers were correlated
      with increased oxidative stress, and both were associated with low cognitive
      performance. However, based on multiple linear regression analysis, oxidative
      stress appears to be the main factor responsible for the cognitive decline.
      CONCLUSIONS: The findings suggest that individuals with lower antioxidant status
      are more vulnerable to oxidative stress, which is associated with cognitive
      function, leading to reduced life quality and expectancy.

PMID- 25874024
TI  - Training effects on ROS production determined by electron paramagnetic resonance
      in master swimmers.
AB  - Acute exercise induces an increase in Reactive Oxygen Species (ROS) production
      dependent on exercise intensity with highest ROS amount generated by strenuous
      exercise. However, chronic repetition of exercise, that is, exercise training,
      may reduce exercise-induced oxidative stress. Aim of this study was to evaluate
      the effects of 6-weeks high-intensity discontinuous training (HIDT),
      characterized by repeated variations of intensity and changes of redox potential,
      on ROS production and antioxidant capacity in sixteen master swimmers. Time
      course changes of ROS generation were assessed by Electron Paramagnetic Resonance
      in capillary blood by a microinvasive approach. An incremental arm-ergometer
      exercise (IE) until exhaustion was carried out at both before (PRE) and after
      (POST) training (Trg) period. A significant (P < 0.01) increase of ROS production
      from REST to the END of IE in PRE Trg (2.82 +/- 0.66 versus 3.28 +/- 0.66
      umol.min(-1)) was observed. HIDT increased peak oxygen consumption (36.1 +/- 4.3
      versus 40.6 +/- 5.7 mL.kg(-1).min(-1) PRE and POST Trg, resp.) and the
      antioxidant capacity (+13%) while it significantly decreased the ROS production
      both at REST (-20%) and after IE (-25%). The observed link between ROS
      production, adaptive antioxidant defense mechanisms, and peak oxygen consumption
      provides new insight into the correlation between ROS response pathways and
      muscle metabolic function. 

PMID- 25874025
TI  - Cardioprotective effects of voluntary exercise in a rat model: role of matrix
      metalloproteinase-2.
AB  - BACKGROUND: Regular exercise at moderate intensity reduces cardiovascular risks.
      Matrix metalloproteinases (MMPs) play a major role in cardiac remodeling,
      facilitating physiological adaptation to exercise. The aim of this study was to
      examine the influence of voluntary physical exercise on the MMP-2 enzyme activity
      and to investigate the cardiac performance by measurement of angina
      susceptibility of the heart, the basal blood pressure, the surviving aorta ring
      contraction, and the cardiac infarct size after I/R-induced injury. METHODS: Male
      Wistar rats were divided into control and exercising groups. After a 6-week
      period, the serum level of MMP-2, basal blood pressure, cardiac angina
      susceptibility (the ST segment depression provoked by epinephrine and 30 s later
      phentolamine), AVP-induced heart perfusion and aorta ring contraction, infarct
      size following 30 min ischemia and 120 min reperfusion, and coronary effluent MMP
      2 activity were measured. RESULTS: Voluntary wheel-running exercise decreased
      both the sera (64 kDa and 72 kDa) and the coronary effluent (64 kDa) MMP-2 level,
      reduced the development of ST depression, improved the isolated heart perfusion,
      and decreased the ratio of infarct size. CONCLUSION: 6 weeks of voluntary
      exercise training preserved the heart against cardiac injury. This protective
      mechanism might be associated with the decreased activity of MMP-2.

PMID- 25874026
TI  - 3-(3-pyridylmethylidene)-2-indolinone reduces the severity of colonic injury in a
      murine model of experimental colitis.
AB  - Nrf2 is the key transcription factor regulating the antioxidant response which is
      crucial for cytoprotection against extracellular stresses. Numerous in vivo
      studies indicate that Nrf2 plays a protective role in anti-inflammatory response.
      3-(3-Pyridylmethylidene)-2-indolinone (PMID) is a synthesized derivative of 2
      indolinone compounds. Our previous study suggested that PMID induces the
      activation of Nrf2/ARE pathway, then protecting against oxidative stress-mediated
      cell death. However, little is known regarding the anti-inflammatory properties
      of PMID in severe inflammatory phenotypes. In the present study we determined if
      PMID treatment protects mice from dextran sodium sulphate- (DSS-) induced
      colitis. The result suggests that treatment with PMID prior to colitis induction
      significantly reduced body weight loss, shortened colon length, and decreased
      disease activity index compared to control mice. Histopathological analysis of
      the colon revealed attenuated inflammation in PMID pretreated animals. The levels
      of inflammatory markers in colon tissue and serum were reduced associated with
      inhibition of NF-kappaB activation. The expression levels of Nrf2-dependent genes
      such as HO-1, NQO1, and Nrf2 were increased in PMID pretreated mice. However,
      PMID pretreatment did not prevent DSS-induced colitis in Nrf2 knockout mice.
      These data indicate that PMID pretreatment in mice confers protection against DSS
      induced colitis in Nrf2-dependent manner, suggesting a potential role of PMID in
      anti-inflammatory response. 

PMID- 25874027
TI  - Influence of toxicologically relevant metals on human epigenetic regulation.
AB  - Environmental toxicants such as toxic metals can alter epigenetic regulatory
      features such as DNA methylation, histone modification, and non-coding RNA
      expression. Heavy metals influence gene expression by epigenetic mechanisms and
      by directly binding to various metal response elements in the target gene
      promoters. Given the role of epigenetic alterations in regulating genes, there is
      potential for the integration of toxic metal-induced epigenetic alterations as
      informative factors in the risk assessment process. Here, we focus on recent
      advances in understanding epigenetic changes, gene expression, and biological
      effects induced by toxic metals. 

PMID- 25874028
TI  - Gambogic Acid Disrupts Toll-like Receptor4 Activation by Blocking
      Lipopolysaccharides Binding to Myeloid Differentiation Factor 2.
AB  - Our body's immune system has defense mechanisms against pathogens such as viruses
      and bacteria. Immune responses are primarily initiated by the activation of toll
      like receptors (TLRs). In particular, TLR4 is well-characterized and is known to
      be activated by gram-negative bacteria and tissue damage signals. TLR4 requires
      myeloid differentiation factor 2 (MD2) as a co-receptor to recognize its ligand,
      lipopolysaccharides (LPS), which is an extracellular membrane component of gram
      negative bacteria. Gambogic acid is a xanthonoid isolated from brownish or orange
      resin extracted from Garcinia hanburyi. Its primary effect is tumor suppression.
      Since inflammatory responses are related to the development of cancer, we
      hypothesized that gambogic acid may regulate TLR4 activation. Our results
      demonstrated that gambogic acid decreased the expression of pro-inflammatory
      cytokines (TNF-alpha, IL-6, IL-12, and IL-1beta) in both mRNA and protein levels
      in bone marrow-derived primary macrophages after stimulation with LPS. Gambogic
      acid did not inhibit the activation of Interferon regulatory factor 3 (IRF3)
      induced by TBK1 overexpression in a luciferase reporter gene assay using IFN-beta
      PRD III-I-luc. An in vitro kinase assay using recombinant TBK1 revealed that
      gambogic acid did not directly inhibit TBK1 kinase activity, and instead
      suppressed the binding of LPS to MD2, as determined by an in vitro binding assay
      and confocal microscopy analysis. Together, our results demonstrate that gambogic
      acid disrupts LPS interaction with the TLR4/MD2 complex, the novel mechanism by
      which it suppresses TLR4 activation. 

PMID- 25874029
TI  - Loss of hfe function reverses impaired recognition memory caused by olfactory
      manganese exposure in mice.
AB  - Excessive manganese (Mn) in the brain promotes a variety of abnormal behaviors,
      including memory deficits, decreased motor skills and psychotic behavior
      resembling Parkinson's disease. Hereditary hemochromatosis (HH) is a prevalent
      genetic iron overload disorder worldwide. Dysfunction in HFE gene is the major
      cause of HH. Our previous study has demonstrated that olfactory Mn uptake is
      altered by HFE deficiency, suggesting that loss of HFE function could alter
      manganese-associated neurotoxicity. To test this hypothesis, Hfe-knockout (Hfe (
      /-)) and wild-type (Hfe (+/+)) mice mice were intranasally-instilled with
      manganese chloride (MnCl2 5 mg/kg) or water daily for 3 weeks and examined for
      memory function. Olfactory Mn diminished both short-term recognition and spatial
      memory in Hfe (+/+) mice, as examined by novel object recognition task and Barnes
      maze test, respectively. Interestingly, Hfe (-/-) mice did not show impaired
      recognition memory caused by Mn exposure, suggesting a potential protective
      effect of Hfe deficiency against Mn-induced memory deficits. Since many of the
      neurotoxic effects of manganese are thought to result from increased oxidative
      stress, we quantified activities of anti-oxidant enzymes in the prefrontal cortex
      (PFC). Mn instillation decreased superoxide dismutase 1 (SOD1) activity in Hfe
      (+/+) mice, but not in Hfe (-/-) mice. In addition, Hfe deficiency up-regulated
      SOD1 and glutathione peroxidase activities. These results suggest a beneficial
      role of Hfe deficiency in attenuating Mn-induced oxidative stress in the PFC.
      Furthermore, Mn exposure reduced nicotinic acetylcholine receptor levels in the
      PFC, indicating that blunted acetylcholine signaling could contribute to impaired
      memory associated with intranasal manganese. Together, our model suggests that
      disrupted cholinergic system in the brain is involved in airborne Mn-induced
      memory deficits and loss of HFE function could in part prevent memory loss via a
      potential up-regulation of anti-oxidant enzymes in the PFC. 

PMID- 25874030
TI  - Ethnic Differences in the Metabolism of Toluene: Comparisons between Korean and
      Foreign Workers Exposed to Toluene.
AB  - The objectives of this study were to investigate the individual characteristics,
      lifestyle habits, exposure levels, and genetic diversity of xenobiotic
      metabolizing enzymes involved in toluene metabolism in Korean and foreign workers
      exposed to toluene at a manufacturing plant. This study was conducted to
      determine the effects of culture or ethnicity on toluene metabolism. The results
      showed that blood and urinary toluene concentrations were dependent on the level
      of exposure to toluene. We analyzed the correlation between toluene metabolism
      and genetic diversity in glutathione S-transferase (GST) (M1), GSTT1, and
      cytochrome p-450 (CYP) 2E1*5 as well as lifestyle habits (smoking, drinking, and
      exercise habits). The results revealed significant correlations between toluene
      metabolism and GSTM1 and GSTT1 genetic diversity, as well as smoking and
      exercise. 

PMID- 25874031
TI  - Improved Therapeutic Profiles of PLA2-Free Bee Venom Prepared by Ultrafiltration
      Method.
AB  - Bee venom (BV) has long been used in traditional Eastern and Western medicine for
      chronic inflammation, pain and skin therapy. Human exposure to BV, however, often
      causes unwanted adverse effects and is even fatal in some cases. Phospholipase A2
      (PLA2) of BV is now suspected to play a key role in these adverse effects. We
      investigated the potential use of PLA2-free bee venom (PBV) as a replacement for
      BV in cosmetic products. PBV prepared by molecular weight cut-off ultrafiltration
      exhibits a superior profile in comparison with regular BV, by inhibiting elastase
      activity and suppressing the induction of nitric oxide (NO) and metalloproteinase
      9 (MMP-9), while retaining the effects of cell proliferation and protection
      against ultraviolet B (UVB)-induced damage in human dermal fibroblast cells. PBV
      thus appears to be more promising than BV as a cosmetic ingredient with a reduced
      potential for adverse reactions in the recipient. 

PMID- 25874032
TI  - Safety assessment of mainstream smoke of herbal cigarette.
AB  - Owing to the increase in price of cigarettes in Korea, herbal cigarettes have
      received increasing attention as a non-smoking aid; however, its safety has
      hardly been studied. We analyzed some of the toxic components in the mainstream
      smoke of herbal cigarettes, performed a mutagenicity test on smoke condensates
      for safety assessment, and compared the results with the corresponding values of
      a general cigarette with the same tar content. Herbal cigarette "A" was smoked
      using automatic smoking machine under ISO conditions in a manner similar to
      general cigarette "T". The tar content measured was higher than that inscribed on
      the outside of a package. The mainstream smoke of herbal cigarette "A" did not
      contain detectable levels of tobacco-specific nitrosamines and nicotine. Carbon
      monoxide and benzo(alpha)pyrene contents in herbal cigarette "A" were higher than
      those in the general cigarette "T". The phenolic contents such as hydroquinone,
      resorcinol, and catechol in herbal cigarette "A" were higher than those in the
      general cigarette "T", but cresol contents in herbal cigarette "A" were lower
      than those in the general cigarette "T". The content of aromatic amines such as 4
      aminobiphenyl in herbal cigarette "A" was higher than that in the general
      cigarette "T"; however, this difference was not statistically significant. On the
      other hand, 1-aminonaphthalene, 2-aminonaphthalene, and 3-aminobiphenyl contents
      in herbal cigarette "A" were lower than those in the general cigarette "T". The
      smoke condensates of herbal cigarette "A" exhibited a higher mutagenic potential
      than the condensates from the general cigarette "T" at the same concentration. We
      concluded that the mainstream smoke of herbal cigarette contains some toxic
      components, the smoke condensates of herbal cigarettes are mutagenic similar to
      general cigarette because of combustion products, and that the evaluation of the
      chemical and biological safety of all types of herbal cigarettes available on the
      market. 

PMID- 25874033
TI  - Assessing the systemic toxicity in rabbits after sub acute exposure to ocular
      irritant chemicals.
AB  - Eye is a highly vascularised organ. There are chances that a foreign substance
      can enter the systemic circulation through the eye and cause oxidative stress and
      evoke immune response. Here the eyes of rabbits were exposed, for a period of 7
      days, to 5 known ocular irritants: Cetyl pyridinium chloride (CPC), sodium
      salicylate (SS), imidazole (IMI), acetaminophen (ACT) and nicotinamide (NIC). The
      eyes were scored according to the draize scoring. Blood collected from the
      treated rabbit were analyzed for haematological and biochemical parameters. After
      sacrifice, histological analysis of the eye and analysis of pro-inflammatory
      biomarkers (IL-1alpha, IL-1beta, IL-8 and TNF-alpha) in the cornea using ELISA
      was carried out. Spleen was collected and the proliferation capacities of
      spleenocytes were analyzed. Liver and brain were collected and assessed for
      oxidative stress. The eye irritation potential of the chemicals was evident from
      the redness and swelling of the conjunctiva and cornea. Histopathological
      analysis and ELISA assay showed signs of inflammation in the eye. However, the
      haematological and biochemical parameters showed no change. Spleenocyte
      proliferations showed only slight alterations which were not significant. Also
      oxidative stress in the brain and liver were negligible. In conclusion, chemicals
      which cause ocular irritation and inflammation did not show any systemic side
      effects in the present scenario. 

PMID- 25874034
TI  - Single oral dose toxicity test of blue honeysuckle concentrate in mice.
AB  - The objective of this study was to obtain single oral dose toxicity information
      for concentrated and lyophilized powder of blue honeysuckle (Lonicera caerulea
      L., Caprifoliaceae; BHcL) in female and male ICR mice to aid in the process of
      developing natural origin medicinal ingredients or foods following proximate
      analysis and phytochemical profile measurement. The proximate analysis revealed
      that BHcL had an energy value of 3.80 kcal/g and contained 0.93 g/g of
      carbohydrate, 0.41 g/g of sugar, 0.02 g/g of protein, and 0.20 mg/g of sodium.
      BHcL did not contain lipids, including saturated lipids, trans fats, or
      cholesterols. Further, BHcL contained 4.54% of betaine, 210.63 mg/g of total
      phenols, 159.30 mg/g of total flavonoids, and 133.57 mg/g of total anthocyanins.
      Following administration of a single oral BHcL treatment, there were no treatment
      related mortalities, changes in body weight (bw) or organ weight, clinical signs,
      necropsy or histopathological findings up to 2,000 mg/kg bw, the limited dosage
      for rodents of both sexes. We concluded that BHcL is a practically non-toxic
      material in toxicity potency. 

PMID- 25874035
TI  - Subchronic Oral Dose Toxicity of Freeze-dried Powder of Allomyrina dichotoma
      Larvae.
AB  - The objective of this study was to investigate the toxicological information of
      freeze-dried powder from Allomyrina dichotoma (A. dichotoma) larvae as a food
      ingredient. The powder, suspended in distilled water, was administered once daily
      by oral gavage to four groups of Sprague-Dawley (SD) rats at dose levels of 0
      (vehicle control), 250, 850, and 2500 mg/kg/day. After 13 wks of repeated
      administration, the standard toxicological parameters such as mortality, clinical
      signs, body weight, food consumption, ophthalmologic examination, clinical
      pathology, organ weights and macro/microscopic examination were applied for
      assessment of general toxicity. In addition, serum IgE and histamine levels were
      determined to evaluate allergenicity. The freeze-dried powder from A. dichotoma
      larvae did not produce treatmentrelated changes or findings in any toxicological
      parameters in either sex of any dosed groups except for slight increases in serum
      histamine levels at 2500 mg/kg/day. The changes were considered not to be adverse
      since the magnitude was minimal. In conclusion, the NOAEL (No Observed Adverse
      Effect Level) of the freeze-dried powder from A. dichotoma larvae was determined
      to be 2500 mg/kg/day or more in both sexes of SD rats and it is considered a
      candidate to be edible material. 

PMID- 25874036
TI  - Single- and Repeat-dose Oral Toxicity Studies of Lithospermum erythrorhizon
      Extract in Dogs.
AB  - Lithospermum erythrorhizon has long been used in traditional Asian medicine for
      the treatment of diseases, including skin cancer. The oral toxicity of a hexane
      extract of Lithospermum erythrorhizon root (LEH) was investigated in Beagle dogs
      by using single escalating doses, two-week dose range-finding, and 4-week oral
      repeat dosing. In the single dose-escalating oral toxicity study, no animal died,
      showed adverse clinical signs, or changes in body weight gain at LEH doses of up
      to 2,000 mg/kg. In a 2 week dose range-finding study, no treatment-related
      adverse effects were detected by urinalysis, hematology, blood biochemistry,
      organ weights, or gross and histopathological examinations at doses of up to 500
      mg LEH/kg/day. In the 4 week repeat-dose toxicity study, a weight loss or
      decreased weight gain was observed at 300 mg/kg/day. Although levels of serum
      triglyceride and total bilirubin were increased in a dose dependent manner, there
      were no related morphological changes. Based on these findings, the sub-acute no
      observable adverse effect level for 4-week oral administration of LEH in Beagles
      was 100 mg/kg/day. 

PMID- 25874037
TI  - Pediatric urology in the KJU.

PMID- 25874038
TI  - Prospects of stem cell treatment in benign urological diseases.
AB  - Stem cells (SCs) are undifferentiated cells that are capable of self-renewal and
      differentiation and that therefore contribute to the renewal and repair of
      tissues. Their capacity for division, differentiation, and tissue regeneration is
      highly dependent on the surrounding environment. Several preclinical and clinical
      studies have utilized SCs in urological disorders. In this article, we review the
      current status of SC use in benign urological diseases (erectile dysfunction,
      Peyronie disease, infertility, and urinary incontinence), and we summarize the
      results of the preclinical and clinical trials that have been conducted. 

PMID- 25874040
TI  - How much progress has been made in journal metrics two years after the citation
      analysis of the Korean Journal of Urology?
AB  - PURPOSE: In April 2013, the journal metrics of the Korean Journal of Urology
      (KJU) were reported. That report showed tremendous improvement from the point of
      view of journal metrics. Two years later, the same metrics were reanalyzed to
      determine the present position of the KJU among the international journals in the
      Web of Science. MATERIALS AND METHODS: I analyzed journal metrics of the KJU such
      as impact factor, total citations, and h-index by use of the same methods as in
      the previous report. RESULTS: Total citations in the Web of Science were 332 in
      2012, 439 in 2013, and 578 in 2014. Manually calculated impact factors from 2012
      to 2014 were 0.770, 0.824, and 0.751, respectively. There was an increase in the
      h-index from 8 in 2012 to 11 in February 2015. Editorial board members were from
      15 countries in 2014. Authors of KJU articles were from 21 countries in 2014.
      CONCLUSIONS: During 2 years, remarkable progress was made in KJU's citation
      indicators and in the diversity of the authors' and editorial board members'
      countries.

PMID- 25874039
TI  - A current perspective on geriatric lower urinary tract dysfunction.
AB  - Lower urinary tract dysfunction-such as urinary incontinence (UI), detrusor
      overactivity, and benign prostatic hyperplasia-is prevalent in elderly persons.
      These conditions can interfere with daily life and normal functioning and lead to
      negative effects on health-related quality of life. UI is one of the most common
      urologic conditions but is poorly understood elderly persons. The overall
      prevalence of UI increases with age in both men and women. Elderly persons often
      neglect UI or dismiss it as part of the normal aging process. However, UI can
      have significant negative effects on self-esteem and has been associated with
      increased rates of depression. UI also affects quality of life and activities of
      daily living. Although UI is more common in elderly than in younger persons, it
      should not be considered a normal part of aging. UI is abnormal at any age. The
      goal of this review is to provide an overview of the cause, classification,
      evaluation, and management of geriatric lower urinary tract dysfunction. 

PMID- 25874041
TI  - Use of nanoparticles to monitor human mesenchymal stem cells transplanted into
      penile cavernosum of rats with erectile dysfunction.
AB  - PURPOSE: This study was performed to examine the treatment of erectile
      dysfunction by use of superparamagnetic iron oxide nanoparticles-labeled human
      mesenchymal stem cells (SPION-MSCs) transplanted into the cavernous nerve injured
      cavernosa of rats as monitored by molecular magnetic resonance imaging (MRI).
      MATERIALS AND METHODS: Eight-week-old male Sprague-Dawley rats were divided into
      three groups of 10 rats each: group 1, sham operation; group 2, cavernous nerve
      injury; group 3, SPION-MSC treatment after cavernous nerve injury. Immediately
      after the cavernous nerve injury in group 3, SPION-MSCs were injected into the
      cavernous nerve injured cavernosa. Serial T2-weighted MRI was done immediately
      after injection and at 2 and 4 weeks. Erectile response was assessed by cavernous
      nerve stimulation at 2 and 4 weeks. RESULTS: Prussian blue staining of SPION-MSCs
      revealed abundant uptake of SPION in the cytoplasm. After injection of 1*10(6)
      SPION-MSCs into the cavernosa of rats, T2-weighted MRI showed a clear hypointense
      signal induced by the injection. The presence of SPION in the corpora cavernosa
      was confirmed with Prussian blue staining. At 2 and 4 weeks, rats with cavernous
      nerve injury had significantly lower erectile function than did rats without
      cavernous nerve injury (p<0.05). The group transplanted with SPION-MSCs showed
      higher erectile function than did the group without SPION-MSCs (p<0.05). The
      presence of SPION-MSCs for up to 4 weeks was confirmed by MRI imaging and
      Prussian blue staining in the corpus cavernosa. CONCLUSIONS: Transplanted SPION
      MSCs existed for up to 4 weeks in the cavernous nerve injured cavernosa of rats.
      Erectile dysfunction recovered and could be monitored by MRI.

PMID- 25874042
TI  - Prevalence and clinical significance of incidental (18)F-fluoro-2-deoxyglucose
      uptake in prostate.
AB  - PURPOSE: To investigate the prevalence and clinical significance of incidental
      prostate fluoro-2-deoxyglucose (FDG) uptake and to evaluate its impact on patient
      management. MATERIALS AND METHODS: Of 47,109 men who underwent FDG positron
      emission tomography between 2004 and 2014, 1,335 (2.83%) demonstrated incidental
      FDG uptake in the prostate, with 99 of the latter undergoing prostate biopsy. The
      primary end point was the histological presence of prostate adenocarcinoma in the
      biopsy specimen. Outcomes, including treatment methods, survival, and causes of
      death, were also assessed. Factors associated with the diagnosis of prostate
      cancer were evaluated by using logistic regression analysis. RESULTS: Patients
      with prostate cancer were more likely to have higher serum prostate-specific
      antigen (PSA) (p=0.001) and focal FDG uptake (p=0.036) than were those without.
      Prostate cancer occurred in 1 of 26 patients (3.8%) with serum PSA<2.5 ng/mL,
      compared with 40 of 67 patients (59.7%) with serum PSA>=2.5 ng/mL. Multivariable
      analysis showed that focal lesions (odds ratio [OR], 5.50; p=0.038), age (OR,
      1.06; p=0.031), and serum PSA (OR, 1.28; p=0.001) were independent predictors of
      prostate cancer diagnosis. Most patients with prostate cancer had organ-confined
      tumors. Of these, 12 (29.3%) underwent radical prostatectomy and 25 (60.9%)
      received hormone therapy. Of the 11 patients who died, 9 died of primary cancer
      progression, with only 1 patient dying from prostate cancer. CONCLUSIONS: The
      prevalence of incidental FDG uptake in the prostate was not high, although
      patients with elevated serum PSA had a higher incidence of prostate cancer.
      Patients with FDG uptake in the prostate should be secondarily evaluated by
      measuring serum PSA, with those having high serum PSA undergoing prostate biopsy.

PMID- 25874043
TI  - The prognostic impact of perioperative blood transfusion on survival in patients
      with bladder urothelial carcinoma treated with radical cystectomy.
AB  - PURPOSE: The aim of our study was to assess the influence of perioperative blood
      transfusion (PBT) on survival outcomes following radical cystectomy (RC) and
      pelvic lymph node dissection (PLND). MATERIALS AND METHODS: We reviewed and
      analyzed the clinical data of 432 patients who underwent RC for bladder cancer
      from 1991 to 2012. PBT was defined as the transfusion of allogeneic red blood
      cells during RC or postoperative hospitalization. RESULTS: Of all patients, 315
      patients (72.9%) received PBT. On multivariate logistic regression analysis,
      female gender (p=0.015), a lower preoperative hemoglobin level (p=0.003),
      estimated blood loss>800 mL (p<0.001), and performance of neoadjuvant
      chemotherapy (p<0.001) were independent risk factors related to requiring
      perioperative transfusions. The receipt of PBT was associated with increased
      overall mortality (hazard ratio, 1.91; 95% confidence interval, 1.25-2.94;
      p=0.003) on univariate analysis, but its association was not confirmed by
      multivariate analysis (p=0.058). In transfused patients, a transfusion of >4
      packed red blood cell units was an independent predictor of overall survival
      (p=0.007), but not in cancer specific survival. CONCLUSIONS: Our study was not
      conclusive to detect a clear association between PBT and survival after RC.
      However, the efforts should be made to continue limiting the overuse of
      transfusion especially in patients who are expected to have a high probability of
      PBT, such as females and those with a low preoperative hemoglobin level and
      history of neoadjuvant chemotherapy.

PMID- 25874044
TI  - Significance of intraprostatic architecture and regrowth velocity for considering
      discontinuation of dutasteride after combination therapy with an alpha blocker: a
      prospective, pilot study.
AB  - PURPOSE: We conducted a prospective single-center study to evaluate the
      possibility of discontinuation of dutasteride after combination therapy with an
      alpha blocker for benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: We
      prospectively treated BPH patients with an alpha blocker and dutasteride (0.5
      mg/d). Patients who had been treated with alpha blockers against BPH for more
      than 2 months were eligible, and 20 patients were included in the study. After 6
      months of combination therapy, dutasteride was discontinued. Patients were
      followed for 12 months after cessation. Prostate volume, intraprostatic
      architecture determined by transrectal ultrasound, peak urinary flow rate,
      postvoid residual urine volume, and the serum prostate-specific antigen level
      were evaluated every 6 months, and the International Prostate Symptom Score and
      overactive bladder symptom score (OABSS) every 3 months. Patients were allowed to
      restart dutasteride during the follow-up period according to their desire.
      RESULTS: Twelve patients (12/20, 60%) restarted the combination therapy from 6 to
      12 months into the follow-up period. For patients who restarted dutasteride, the
      prostate volume and OABSS had increased and worsened after discontinuation,
      respectively. A visible transition zone with a clear border on transrectal
      ultrasound at baseline and regrowth of the prostate after discontinuation of
      dutasteride were risk factors for restarting the therapy (Mann-Whitney U test:
      p=0.008, p=0.017). CONCLUSIONS: Prostatic enlargement after discontinuation of
      dutasteride differs among patients. Rapid regrowth of the prostate leads to
      deterioration of storage symptoms and a tendency to restart dutasteride. Baseline
      intraprostatic architecture may be a predictive factor for whether the patient is
      a good candidate for discontinuation.

PMID- 25874045
TI  - Elderly men over 65 years of age with late-onset hypogonadism benefit as much
      from testosterone treatment as do younger men.
AB  - PURPOSE: To investigate the potential benefits of testosterone administration to
      elderly men (>65 years) with late-onset hypogonadism (LOH) in comparison with
      younger men and to assess the safety of testosterone administration to elderly
      men. MATERIALS AND METHODS: A total of 561 hypogonadal men from two registry
      studies were divided into age groups of <=65 years (group Y, n=450; range, 32-65
      years) and >65 years (group O, n=111; range, 66-84 years). Following an initial 6
      week interval, all men were treated with 3-month injections of parenteral
      testosterone undecanoate for up to 6 years. RESULTS: Over the 6 years, there was
      a progressive decrease of body weight and waist circumference. Beneficial effects
      on lipids and other metabolic factors and on psychological and sexual functioning
      progressed over the first 24 to 42 months and were sustained. Rather than a
      deterioration, there was an improvement of urinary parameters. Prostate volume
      and prostate-specific antigen increased moderately. Hematocrit levels increased
      but remained within safe margins. CONCLUSIONS: The benefits of restoring serum
      testosterone in men with LOH were not significantly different between men older
      than 65 years of age and younger men. There were no indications that side effects
      were more severe in elderly men. The effects on prostate and urinary function and
      hematocrit were within safe margins. Age itself need not be a contraindication to
      testosterone treatment of elderly men with LOH.

PMID- 25874046
TI  - Changes of calcific density in pediatric patients with testicular microlithiasis.
AB  - PURPOSE: Testicular microlithiasis (TM) is a relatively rare clinical entity of
      controversial significance characterized by the existence of hydroxyapatite
      microliths located in the seminiferous tubules. The aim of this study was to
      observe the natural course of changes in the calcific density of pediatric TM.
      MATERIALS AND METHODS: We included a total of 23 TM patients undergoing scrotal
      ultrasound (US) on at least two occasions from July 1997 to August 2014. We
      retrospectively analyzed the patient characteristics, clinical manifestations,
      specific pathological features, and clinical outcomes. We measured the calcified
      area and compared the calcific density between the initial and final USs.
      RESULTS: The mean age at diagnosis was 11.3+/-4.6 years, and the follow-up period
      was 79.1+/-38.8 months (range, 25.4-152.9 months). During the follow-up period,
      no patients developed testicular cancer. Calcific density on US was increased in
      the last versus the initial US, but not to a statistically significant degree
      (3.74%+/-6.0% vs. 3.06%+/-4.38%, respectively, p=0.147). When we defined groups
      with increased and decreased calcification, we found that diffuse TM was
      categorized into the increased group to a greater degree than focal TM (10/20 vs.
      4/23, respectively, p=0.049). In addition, five of eight cases of cryptorchidism
      (including two cases of bilateral cryptorchidism) were categorized in the
      increased calcification group. CONCLUSIONS: Diffuse TM and cryptorchidism tend to
      increase calcific density. Close observation is therefore recommended for cases
      of TM combined with cryptorchidism and cases of diffuse TM.

PMID- 25874047
TI  - Predictive role of hematologic parameters in testicular torsion.
AB  - PURPOSE: To evaluate the predictive role of the neutrophil to lymphocyte ratio
      (NLR), platelet to lymphocyte ratio (PLR), mean platelet volume (MPV), and
      platelet count (PLT) in the diagnosis of testicular torsion (TT) and testicular
      viability following TT. MATERIALS AND METHODS: We analyzed two study groups in
      this retrospective study: 75 patients with a diagnosis of TT (group 1) and 56 age
      matched healthy subjects (group 2). We performed a complete blood count as a part
      of the diagnostic procedure, and NLR, PLR, MPV, and PLT values were recorded. We
      compared the patient and control groups in terms of these parameters. Then, TT
      patients were divided into two subgroups according to the time elapsed since the
      onset of symptoms. Subsequently, we evaluated the relationship between the
      duration of symptoms and these parameters. RESULTS: There were significant
      differences between groups 1 and 2 in NLR, PLR, and PLT (p<0.001 for all). There
      was no predictive role of MPV in the diagnosis of TT (p=0.328). We determined
      significantly high sensitivity and specificity levels for NLR in the prediction
      of TT diagnosis (84% and 92%, respectively). Furthermore, NLR was significantly
      related to the duration of symptoms in TT patients (p=0.01). CONCLUSIONS: NLR may
      be a useful parameter in the diagnosis of TT. Furthermore, NLR may be used as a
      predictive factor for testicular viability following TT.

PMID- 25874048
TI  - Right sided double inferior vena cava with obstructed retrocaval ureter: Managed
      with single incision multiple port laparoscopic technique using "Santosh
      Postgraduate Institute tacking ureteric fixation technique".
AB  - Right double inferior vena cava with obstructed retrocaval ureter is an extremely
      rare anomaly with only a few reported cases in the literature. To the best of our
      knowledge, this is the first case report describing ureteric repair by use of a
      single-incision laparoscopic technique. In addition, this report addresses the
      underlying surgical challenges of this repair and provides a brief review of the
      embryology of this anomaly. The "Santosh Postgraduate Institute ureteric tacking
      fixation technique" provides ease of end-to-end uretero-ureteric anastomosis in a
      single-incision laparoscopic surgery. 

PMID- 25874050
TI  - The prevalence of female sexual dysfunction among migraine patients.
AB  - BACKGROUND: Female sexual dysfunction (FSD) defines as any disorder in the
      process of sexual contact including 6 main domains, desire, arousal, lubrication,
      orgasm, orgasm satisfaction and pain. This study was conducted to evaluate
      prevalence of sexual dysfunction disorder in women with migraine headache and
      also find the associated factors related to migraine characteristics. METHODS: A
      total of 69 eligible woman patients fulfilling criteria for migraine participated
      in this study. The Female Sexual Function Index (FSFI), a multi-dimensional self
      report implement for appraisal of Female Sexual Function during the past month
      were utilized in this study. The information related to migraine including
      frequency, duration of headache attack, severity of headache according to visual
      analog scale (VAS) score and headache impact test (HIT) score were obtained using
      a self-administrated questionnaire. RESULTS: About 68.4% of patients had an FSFI
      score < 28. In domains of desire 73.7%, arousal 64.9%, lubrication 21.1%, orgasm
      33.3%, satisfaction 17.5%, and pain 40.4% of patients reported some degree of
      dysfunction. Among variables related to migraine characteristics, only a
      significant association between frequency and sexual dysfunction were recorded (P
      < 0.05). CONCLUSION: FSD is prevalent among migraine patients. The frequency of a
      migraine attack is associated with FSD. Serotonin mechanisms such as 5HT2, 5HT3
      agonist have been hypothesized as a shared etiology for migraine and sexual
      dysfunction.

PMID- 25874049
TI  - Epileptic syndromes: From clinic to genetic.
AB  - Epilepsy is one of the most common neurological disorders. Studies have
      demonstrated that genetic factors have a strong role in etiology of epilepsy.
      Mutations in genes encoding ion channels, neurotransmitters and other proteins
      involved in the neuronal biology have been recognized in different types of this
      disease. Moreover, some chromosomal aberration including ring chromosomes will
      result in epilepsy. In this review, we intend to highlight the role of molecular
      genetic in etiology of epilepsy syndromes, inspect the most recent classification
      of International League against Epilepsy and discuss the role of genetic
      counseling and genetic testing in management of epilepsy syndromes. Furthermore,
      we emphasize on collaboration of neurologists and geneticists to improve
      diagnosis and management. 

PMID- 25874051
TI  - A novel effect of Noscapine on patients with massive ischemic stroke: A pseudo
      randomized clinical trial.
AB  - BACKGROUND: Massive ischemic stroke causes significant mortality and morbidity in
      stroke patients. The main treatments for massive ischemic stroke are recombinant
      tissue plasminogen activator (rtPA), craniotomy, and endovascular interventions.
      Due to destructive effects of bradykinin on the nervous system in ischemic
      stroke, it seems reasonable that using Noscapine as a Bradykinin antagonist may
      improve patients' outcome after ischemic stroke. The effect of Noscapine on
      massive ischemic stroke was shown by the previous pilot study by our group. This
      pseudo-randomized clinical trial study was designed to assess the result of the
      pilot study. METHODS: Patients who had clinical symptoms or computed tomography
      scan indicative of massive stroke (in full middle cerebral artery territory) were
      entered to the study. The cases received the drugs according to their turns in
      emergency ward (pseudo-randomized). The patient group received Noscapine, and the
      control group received common supportive treatments. The patients and data
      analyzer were blinded about the data. At the end of the study, to adjust
      confounding variables we used logistic regression. RESULTS: After 1-month follow
      up, 16 patients in the control group and 11 patients in the case group expired (P
      = 0.193). Analyzing the data extracted from Rankin scale and Barthel index check
      lists, revealed no significant differences in the two groups. CONCLUSION: Despite
      the absence of significant statistical results in our study, the reduction rate
      of 16% for mortality rate in Noscapine recipients is clinically remarkable and
      motivates future studies with larger sample sizes.

PMID- 25874052
TI  - Serum 25(OH) Vitamin D levels is not associated with disability in multiple
      sclerosis patients: A case-control study.
AB  - BACKGROUND: It seems that serum vitamin D levels are one of the potential
      environmental factors affecting the severity of multiple sclerosis (MS). In this
      study, we aim to evaluate vitamin D levels in MS patients and healthy subjects
      and assess the relationship between vitamin D level and disability. METHODS: In
      this case-control study, 168 rapid relapsing MS patients and 168 matched healthy
      controls were randomly included in this study. Demographic characteristics and
      serum vitamin D levels for patients and controls, as well as expanded disability
      status scale (EDSS), duration of disease and diagnostic lag for patients were
      evaluated. We followed up patients for 6 months and relapses were recorded.
      RESULTS: The mean serum vitamin D levels were 19.16 +/- 17.37 inpatients and
      25.39 +/- 19.67 in controls (P = 0.560). The mean serum vitamin D levels were
      12.65 +/- 13.3 in patients with relapses and 22.08 +/- 18.22 in patients without
      any relapses (P < 0.001). There was no significant correlation between EDSS score
      and serum vitamin D levels (r = -0.08, P = 0.280). There was a significant
      positive correlation between EDSS score and disease duration (r = 0.52, P <
      0.001). CONCLUSION: In conclusion, vitamin D level in patients with MS was
      significantly lower than the healthy subjects, but no significant relationship
      was found between vitamin D levels and disability. Our findings did not suggest a
      protective role for serum vitamin D levels against disability.

PMID- 25874053
TI  - Comparison of endovascular coiling and surgical clipping for the treatment of
      intracranial aneurysms: A prospective study.
AB  - BACKGROUND: Management of intracranial aneurysms has made debates about the best
      treatment modality in recent years. The aim of this study was to compare the
      interventional outcomes between two groups of patients, one treated with
      endovascular coiling and the other treated with surgical clipping. METHODS: This
      prospective study included 48 patients with intracranial aneurysms who underwent
      endovascular coiling (27 patients) or surgical clipping (21 patients) from July
      2011 to August 2013. A neurologist examined patients in admission and followed
      them by phone call 1-year after intervention. RESULTS: Mean modified Rankin Scale
      (MRS) score at the time of admission in endovascular group was 2.86 +/- 0.974
      whereas it was 3.81 +/- 1.078 in surgical clipping group (P = 0.0040). Focal
      neurologic signs were higher in clipping during procedures (P = 0.0310). Of 37
      patients who followed up for a year, 19 were in endovascular group and 18 in
      surgical clipping group. At 1 year follow-up, MRS improvement was statistically
      significant in coiling group (P = 0.0090), but not in clipping group (P =
      0.8750). Mean difference of MRS score at the time of admission and at one year
      later, was 0.947 +/- 1.224 in endovascular group and 0.111 +/- 2.083 in surgical
      group (P = 0.3000). CONCLUSION: There was no statistically significant difference
      at 1 year outcome between two groups. We recommend further interventional studies
      with larger sample sizes for better evaluation of the modalities.

PMID- 25874054
TI  - Accuracy of magnetic resonance spectroscopy in distinction between radiation
      necrosis and recurrence of brain tumors.
AB  - BACKGROUND: Distinction between radiation necrosis and recurrence of
      intraparenchymal tumors is necessary to select the appropriate treatment, but it
      is often difficult based on imaging features alone. We developed an algorithm for
      analyzing magnetic resonance spectroscopy (MRS) findings and studied its accuracy
      in differentiation between radiation necrosis and tumor recurrence. METHODS:
      Thirty-three patients with a history of intraparenchymal brain tumor resection
      and radiotherapy, which had developed new enhancing lesion were evaluated by MRS
      and subsequently underwent reoperation. Lesions with Choline (Cho)/N-acetyl
      aspartate (NAA) > 1.8 or Cho/Lipid > 1 were considered as tumor recurrence and
      the remaining as radiation necrosis. Finally, pre-perative MRS diagnoses were
      compared with histopathological report. RESULTS: The histological diagnosis was
      recurrence in 25 patients and necrosis in 8 patients. Mean Cho/NAA in recurrent
      tumors was 2.72, but it was 1.46 in radiation necrosis (P < 0.01). Furthermore,
      Cho/Lipid was significantly higher in recurrent tumors (P < 0.01) with the mean
      of 2.78 in recurrent tumors and 0.6 in radiation necrosis. Sensitivity,
      specificity, and diagnostic accuracy of the algorithm for detecting tumor
      recurrence were 84%, 75% and 81%, respectively. CONCLUSION: MRS is a safe and
      informative tool for differentiating between tumor recurrence and radiation
      necrosis.

PMID- 25874055
TI  - Elevated troponin T after acute ischemic stroke: Association with severity and
      location of infarction.
AB  - BACKGROUND: Serum troponin elevation, characteristic of ischemic myocardial
      injury, has been observed in some acute ischemic stroke (AIS) patients. Its cause
      and significance are still controversial. The purpose of this study is to find
      determinants of troponin elevation and its relationship with stroke severity and
      location. METHODS: Between January 2013 and August 2013, 114 consecutive AIS
      patients confirmed by diffusion-weighted magnetic resonance imaging were
      recruited in this study. Serum troponin T level was measured as part of routine
      laboratory testing on admission. Ten lead standard electrocardiogram (ECG) was
      performed and stoke severity was assessed based on National Institutes of Health
      Stroke Scale (NIHSS). RESULTS: Troponin T was elevated in 20 (17.6%) of 114
      patients. Patients with elevated troponin were more likely to have higher age,
      higher serum creatinine and ischemic ECG changes. Troponin levels were higher in
      patients with more severe stroke measured by NIHSS [7.96 (6.49-9.78) vs. 13.59
      (10.28-18.00)]. There was no association between troponin and locations of stroke
      and atrial fibrillation. There were 6 (5%) patients with elevated troponin in the
      presence of normal creatinine and ECG. CONCLUSION: Stroke severity, not its
      location, was associated with higher troponin levels. Abnormal troponin levels
      are more likely, but not exclusively, to be due to cardiac and renal causes than
      cerebral ones.

PMID- 25874056
TI  - Proposed equation between flexor carpi radialis H-reflex latency and upper limb
      length.
AB  - BACKGROUND: H-reflex is a valuable electrophysiological technique for assessing
      nerve conduction through entire length of afferent and efferent pathways,
      especially nerve roots and proximal segments of peripheral nerves. The aim of
      this study was to investigate the relation between normal values of flexor carpi
      radialis (FCR) H-reflex latency, upper limb length and age in normal subjects,
      and to determine whether there is any regression equation between them. METHODS:
      By considering the criteria of inclusion and exclusion, 120 upper limbs of 69
      normal volunteers (68 hands of 39 men and 52 hands of 30 women) with the mean age
      of 39.8 +/- 11.2 years participated in this study. FCR H-reflex was obtained by
      standard electrodiagnostic techniques, and its onset latency was recorded. Upper
      limb length and arm length were measured in defined position. The degree of
      association between these variables was determined with Pearson correlation and
      linear regression was used for obtaining the proposed relations. RESULTS: Mean
      FCR H-reflex latency was found to be 15.88 +/- 1.27 ms. There was a direct linear
      correlation between FCR H-reflex latency and upper limb length (r = 0.647) and
      also arm length (r = 0.574), but there was no significant correlation between age
      and FCR H-reflex latency (P = 0.260). Finally, based on our findings, we tried to
      formulate these relations by statistical methods. CONCLUSION: We found that upper
      limb length and arm length are good predictive values for estimation of normal
      FCR H-reflex latency but age, in the range of 20-60 years old, has no correlation
      with its latency. This estimation could have practical indications in pathologic
      conditions.

PMID- 25874057
TI  - Mixed movement disorders revealing an atypical form of creatine deficiency
      syndrome.

PMID- 25874058
TI  - Patent foramen ovale and stroke: Does presence of a migraine headache or any
      character of patent foramen ovale increase the risk of stroke?

PMID- 25874059
TI  - Eating dystonia in a case of neuroacanthocytosis.

PMID- 25874060
TI  - Neurolaw: A brief introduction.
AB  - Neurolaw, as an interdisciplinary field which links the brain to law, facilitates
      the pathway to better understanding of human behavior in order to regulate it
      accurately through incorporating neuroscience achievements in legal studies.
      Since 1990's, this emerging field, by study on human nervous system as a new
      dimension of legal phenomena, leads to a more precise explanation for human
      behavior to revise legal rules and decision-makings. This paper strives to bring
      about significantly a brief introduction to neurolaw so as to take effective
      steps toward exploring and expanding the scope of law and more thorough
      understanding of legal issues in the field at hand. 

PMID- 25874061
TI  - Fungal periprosthetic joint infection in total knee arthroplasty: a systematic
      review.
AB  - Fungal periprosthetic joint infection (PJI) is a rare but devastating
      complication following total knee arthroplasty (TKA). A standardized procedure
      regarding an accurate treatment of this serious complication of knee arthroplasty
      is lacking. In this systematic review, we collected data from 36 studies with a
      total of 45 reported cases of a TKA complicated by a fungal PJI. Subsequently, an
      analysis focusing on diagnostic, medicaments and surgical procedures in the pre-,
      intra- and postoperative period was performed. Candida spp. accounts for about
      80% (36 out of 45 cases) of fungal PJIs and is therefore the most frequently
      reported pathogen. A systemic antifungal therapy was administered in all but one
      patient whereas a local antifungal therapy, e.g. the use of an impregnated
      spacer, is of inferior relevance. Resection arthroplasty with delayed re
      implantation (two-stage revision) was the surgical treatment of choice. However,
      in 50% of all reported cases the surgical therapy was heterogeneous. The outcome
      under a combined therapy was moderate with recurrent fungal PJI in 11 patients
      and subsequent bacterial PJI as a main complication in 5 patients. In summary,
      this systematic review integrates data from up to date 45 reported cases of a
      fungal PJI of a TKA. On the basis of the current literature strategies for the
      treatment of this devastating complication after TKA are discussed. 

PMID- 25874062
TI  - Minimally invasive mini open split-muscular percutaneous pedicle screw fixation
      of the thoracolumbar spine.
AB  - We prospectively assessed the feasibility and safety of a new percutaneous
      pedicle screw (PPS) fixation technique for instrumentation of the thoracic and
      lumbar spine in this study. All patients were operated in the prone position
      under general anesthesia. A 6 to 8 cm midline skin incision was made and wide
      subcutaneous dissection was performed. The paravertebral muscles were first
      dissected subperiosteally into the midline incision of the fascia for lumbar
      microdiscectomy with transforaminal lumbar interbody fusion cage implantation.
      After the secondary paramedian incisions on the fascia, the PPSs were inserted
      via cleavage of the multifidus muscles directly into the pedicles under
      fluoroscopy visualization. A total of 35 patients underwent surgery with this new
      surgical technique. The control group for operative time, blood loss and
      analgesic usage consisted of 35 randomly selected cases from our department. The
      control group underwent surgery via conventional pedicle screw instrumentation
      with paramedian fusion. All patients in the minimal invasive surgery series were
      ambulatory with minimal pain on the first postoperative day. The operation time
      and blood loss and the postoperative analgesic consumption were significantly
      less with this new technique. In conclusion, the minimal invasive mini open split
      muscular percutaneous pedicle screw fixation technique is safe and feasible. It
      can be performed via a short midline skin incision and can also be combined with
      interbody fusion, causing minimal pain without severe muscle damage. 

PMID- 25874063
TI  - Fungal periprosthetic joint infection of the hip: a systematic review.
AB  - Periprosthetic joint infection (PJI) is a severe complication of total joint
      arthroplasty with an incidence of approximately 1%. Due to the high risk of
      persisting infection, successful treatment of fungal PJI is challenging. The
      purpose of this study was to gain insight into the current management of fungal
      PJI of the hip and, by systematically reviewing the cases published so far, to
      further improve the medical treatment of this serious complication of total hip
      arthroplasty. Thus, we conducted a systematic review of the available literature
      concerning fungal PJI in total hip arthroplasty, including 45 cases of fungal
      PJI. At the moment a two-stage revision procedure is favorable and there is an
      ongoing discussion on the therapeutic effect of antifungal drug loaded cement
      spacers on fungal periprosthetic infections of the hip. Due to the fact that
      there is rare experience with it, there is urgent need to establish guidelines
      for the treatment of fungal infections of total hip arthroplasty. 

PMID- 25874064
TI  - The TROJAN Project: Creating a Customized International Orthopedic Training
      Program for Junior Doctors.
AB  - Musculoskeletal problems account for a vast proportion of presentations
      encountered by doctors globally, with figures ranging from 15-36%. However, the
      time medical schools allocate to learning orthopedics is by no means proportional
      to this. This study aims to bridge this gap by developing an international
      orthopedic teaching program tailored to the specific knowledge and skills
      required by junior doctors in different countries. This prospective study asked
      fifty junior doctors, who had recently completed an orthopedics job, what three
      orthopedic teaching topics taught retrospectively would have benefitted their
      clinical practice. The most requested topics were used to design educational
      workshops for junior doctors and these consequently comprised the TROJAN
      (Teaching Requested by Orthopaedic Juniors And Novices) training program. Data
      was collected from twenty-five junior doctors in KwaZulu-Natale State, South
      Africa, and twenty-five in London, UK. It is therefore in these two countries
      that the TROJAN program was subsequently made available. Participants who
      selected topics were within two years of graduating medical school and had worked
      an orthopedic or Accident and Emergency job within the last year. 49% of topics
      chosen by SA doctors were practical skills such as wrist and ankle fracture
      reduction techniques, and management of open fractures. The most requested topic
      by UK doctors (11 out of 25) was management of neck of femur fractures. This is
      rationalized by the fact South African doctors require more hands-on
      responsibility in their daily practice whereas in the UK greater emphasis is
      placed on optimizing patients for theatre and making sound management plans.
      TROJAN currently develops orthopedic skills and knowledge in junior doctors in
      South Africa and United Kingdom with teaching customized based upon location.
      Feedback has been exceptionally positive with every candidate thus far rating the
      usefulness of TROJAN as the highest option, very useful. 

PMID- 25874065
TI  - Can visual aides influence rehabilitation and length of stay following knee
      replacement? A randomized controlled study.
AB  - Arthroplasty is increasingly performed within Australia, with a 2.7% rate
      increase of total knee arthroplasty (TKR) over the last year. With an increasing
      burden on the public health system and increasing waiting lists, all efforts are
      being made to decrease length of stay and improve the post operative
      rehabilitation process. There is currently insufficient evidence to make a
      conclusive statement about visual aids and improved goal attainment post TKR. The
      purpose of this study is to evaluate one such visual aid clinical photographs of
      patients knee range of motion (ROM) pre-and post-operatively and their effect on
      length of stay. Photographs of knee range of motion were obtained pre and post
      operatively while the patient was anesthetized. In this study, a randomized,
      single blinded design allocated patients to either be shown or not shown their
      photographs on day 1 post operatively. Primary outcome measures were the number
      of days the patient remained in hospital. Secondary measures were Western Ontario
      and McMaster Universities Arthritis Index scores, Oxford Knee Scores, American
      Society of Anesthesiologists Score and knee ROM. Thirty-two patients (3
      exclusions) were randomized to the photo group and 27 patients (4 exclusions)
      were randomized to the no photo group. The median length of stay between groups
      was not significantly different. Currently there is not enough evidence to
      conclude that visual aids effect length of stay or rehabilitation pathways.
      Further assessment with larger cohort groups is needed. Preoperative targeting
      and rehabilitation for patients with lower functional status may shorten post
      operative length of patient stay in our institution. 

PMID- 25874066
TI  - Distal femoral complications following antegrade intramedullary nail placement.
AB  - While antegrade nailing for proximal and diaphyseal femur fractures is a commonly
      utilized fixation method with benefits including early mobilization and high
      rates of fracture union, both intraoperative and postoperative complications may
      occur. Intraoperative errors include leg length discrepancy, anterior cortical
      perforation, malreduction of the fracture, and neurovascular injury, and
      postoperative complications include nonunion, malunion, infection, and hardware
      failure. This case series reviews complications affecting the distal femur after
      intramedullary nailing including fracture surrounding a distal femoral
      interlocking screw (Case #1), nonunion after dynamization with nail penetration
      into the knee joint (Case #2), and anterior cortical perforation (Case #3).
      Prevention of intraoperative and postoperative complications surrounding
      intramedullary nailing requires careful study of the femoral anatomy and nail
      design specifications (radius of curvature), consideration of the necessity of
      distal interlocking screws, the need for close radiographic follow-up after nail
      placement with X-rays of the entire length of the nail, and awareness of possible
      nail penetration into the knee joint after dynamization. 

PMID- 25874067
TI  - Mycoplasmal upper respiratory infection presenting as leukocytoclastic
      vasculitis.
AB  - Mycoplasma is a virulent organism that is known to primarily infect the
      respiratory tract; however, affection of the skin, nervous system, kidneys, heart
      and bloodstream has been observed in various forms, which include Stevens Johnson
      syndrome, erythema multiforme, toxic epidermal necrolysis, encephalitis, renal
      failure, conduction system abnormalities and hemolytic anemia. Small vessel
      vasculitis is a lesser-known complication of mycoplasma pneumonia infection. We
      report a case of mycoplasmal upper respiratory tract infection with striking
      cutaneous lesions as the presenting symptom. Mycoplasmal infection was confirmed
      by serology testing, skin biopsy was suggestive of leukocytoclastic vasculitis.
      This case brings forth an uncommon manifestation of mycoplasmal infection with
      extra-pulmonary affection, namely small vessel vasculitis. 

PMID- 25874068
TI  - First detection of human dirofilariasis in South Africa.
AB  - Humans are occasionally inadvertently infected with dirofilariae, the zoonotic
      nematodes. We report two cases of human dirofilariasis in South Africa, an area
      apparently non-endemic for this infection. Dirofilariasis is frequently
      misdiagnosed, so increased awareness of this entity in areas that are non-endemic
      is essential for prevention of inappropriate investigations and invasive therapy.

PMID- 25874069
TI  - Intracellular Pathogens within Alveolar Macrophages in a Patient with HIV
      Infection: Diagnostic Challenge.
AB  - In HIV-infected individuals, macrophages, the key defense effector cells,
      manifest defective activity in their interactions with a wide variety of
      opportunistic pathogens, including fungi and protozoa. Understanding the
      morphological characteristics of intracellular opportunistic pathogens in
      addition to their pathogenesis is of critical importance to provide optimal
      therapy, thereby decreasing morbidity and mortality in HIV-infected patients. We
      herein present a case of disseminated histoplasmosis confused with disseminated
      visceral leishmaniasis in an HIV-infected individual from Guyana who developed
      intracellular organisms within alveolar macrophages. 

PMID- 25874070
TI  - Multi-drug resistant helcococcus-like organism isolated from a chest abscess.
AB  - We report a case of multi-drug resistant Helcococcus-like organism isolated in
      pure culture from a chest abscess in a 31-year-old pregnant woman. 

PMID- 25874071
TI  - Splenic abscesses in a returning traveler.
AB  - Burkholderia, an aerobic gram-negative rod, is the causative organism behind
      melioidosis and is a common soil and water organism found predominantly in South
      East Asia. We report the case of a 68 year-old man returning from an extended
      trip to the Philippines, with splenic hypodense lesions on abdominal computer
      tomography scan, later confirmed to be culture-positive for Burkholderia
      pseudomallei. The patient was treated with a course of intravenous ceftazidime
      followed by eradication therapy with oral doxycycline and trimethoprim
      sulfamethoxazole. He recovered with complete resolution of symptoms at follow up.
      In a returning traveler from an endemic area, melioidosis should be considered as
      part of the differential for any febrile illness with abscesses. 

PMID- 25874072
TI  - Sildenafil and bosentan plasma concentrations in a human immunodeficiency virus-
      infected patient with pulmonary arterial hypertension treated with ritonavir
      boosted protease inhibitor.
AB  - Sildenafil and bosentan are increasingly used for the treatment of pulmonary
      arterial hypertension (PAH) in HIV-infected patients. However, concerns exist
      about pharmacokinetic interactions among sildenafil, bosentan and antiretroviral
      drugs, including protease inhibitors (PI). We describe here the case of an HIV
      infected patient with PAH, who was co-administered bosentan 125 mg twice daily
      and sildenafil 40 mg three times per day, together with a ritonavir-boosted PI
      based antiretroviral therapy; plasma levels of bosentan, sildenafil, N
      desmethylsildenafil, and PI were measured. The patient had a sildenafil Cthrough
      and Cmax of 276.94 ng/mL and 1733.19 ng/mL, respectively. The Cthrough and the
      Cmax of bosentan were 1546.53 ng/mL and 3365.99 ng/mL, respectively. The patient
      was able to tolerate as high sildenafil blood concentrations as 10 times those
      usually requested and did not report any significant adverse reaction to
      sildenafil during the follow-up period. Therapeutic drug monitoring should be
      considered during sildenafil therapy in patients concomitantly treated with
      ritonavir-boosted PI. 

PMID- 25874073
TI  - Mapk/Erk activation in an animal model of social deficits shows a possible link
      to autism.
AB  - BACKGROUND: There is converging preclinical and clinical evidence to suggest that
      the extracellular signal-regulated kinase (ERK) signaling pathway may be
      dysregulated in autism spectrum disorders. METHOD: We evaluated Mapk/Erk1/2,
      cellular proliferation and apoptosis in BTBR mice, as a preclinical model of
      Autism. We had previously generated 410 F2 mice from the cross of BTBR with B6.
      At that time, six different social behaviors in all F2 mice were evaluated and
      scored. In this study, eight mice at each extreme of the social behavioral
      spectrum were selected and the expression and activity levels of Mapk/Erk in the
      prefrontal cortex and cerebellum of these mice were compared. Finally, we
      compared the Mapk/Erk signaling pathway in brain and lymphocytes of the same
      mice, testing for correlation in the degree of kinase activation across these
      separate tissues. RESULTS: Levels of phosphorylated Erk (p-Erk) were
      significantly increased in the brains of BTBR versus control mice. We also
      observed a significant association between juvenile social behavior and
      phosphorylated mitogen-activated protein kinase kinase (p-Mek) and p-Erk levels
      in the prefrontal cortex but not in the cerebellum. In contrast, we did not find
      a significant association between social behavior and total protein levels of
      either Mek or Erk. We also tested whether steady-state levels of Erk activation
      in the cerebral cortex in individual animals correlated with levels of Erk
      activation in lymphocytes, finding a significant relationship for this signaling
      pathway. CONCLUSION: These observations suggest that dysregulation of the ERK
      signaling pathway may be an important mediator of social behavior, and that
      measuring activation of this pathway in peripheral lymphocytes may serve as a
      surrogate marker for central nervous system (CNS) ERK activity, and possibly
      autistic behavior.

PMID- 25874074
TI  - Measuring autistic traits in the general population: a systematic review of the
      Autism-Spectrum Quotient (AQ) in a nonclinical population sample of 6,900 typical
      adult males and females.
AB  - The Autism-Spectrum Quotient (AQ) is a self-report measure of autistic traits. It
      is frequently cited in diverse fields and has been administered to adults of at
      least average intelligence with autism and to nonclinical controls, as well as to
      clinical control groups such as those with schizophrenia, prosopagnosia,
      anorexia, and depression. However, there has been no empirical systematic review
      of the AQ since its inception in 2001. The present study reports a comprehensive
      systematic review of the literature to estimate a reliable mean AQ score in
      individuals without a diagnosis of an autism spectrum condition (ASC), in order
      to establish a reference norm for future studies. A systematic search of
      computerized databases was performed to identify studies that administered the AQ
      to nonclinical participant samples representing the adult male and female general
      population. Inclusion was based on a set of formalized criteria that evaluated
      the quality of the study, the usage of the AQ, and the population being assessed.
      After selection, 73 articles, detailing 6,934 nonclinical participants, as well
      as 1,963 matched clinical cases of ASC (from available cohorts within each
      individual study), were analyzed. Mean AQ score for the nonclinical population
      was 16.94 (95% CI 11.6, 20.0), while mean AQ score for the clinical population
      with ASC was found to be 35.19 (95% CI 27.6, 41.1). In addition, in the
      nonclinical population, a sex difference in autistic traits was found, although
      no sex difference in AQ score was seen in the clinical ASC population. These
      findings have implications for the study of autistic traits in the general
      population. Here, we confirm previous norms with more rigorous data and for the
      first time establish average AQ scores based on a systematic review, for
      populations of adult males and females with and without ASC. Finally, we advise
      future researchers to avoid risk of bias by carefully considering the recruitment
      strategy for both clinical and nonclinical groups and to demonstrate transparency
      by reporting recruitment methods for all participants. 

PMID- 25874075
TI  - Autism spectrum disorder and low vitamin D at birth: a sibling control study.
AB  - BACKGROUND: Insufficient vitamin D activity has attracted increasing interest as
      a possible underlying risk factor in disorders of the central nervous system,
      including autism. METHODS: In this study, 25-hydroxyvitamin D (25(OH)D) was
      analysed in 58 Sweden-born sibling pairs, in which one child had autism spectrum
      disorder (ASD) and the other did not. The study group consisted of two
      representative samples; 47 Gothenburg sibling pairs with mixed ethnicities and 11
      Stockholm sibling pairs with Somali background. 25(OH)D levels were analysed in
      the stored dried blood spots taken in the neonatal period for metabolic
      screening. RESULTS: The collapsed group of children with ASD had significantly
      lower vitamin D levels (M = 24.0 nM, SD = 19.6) as compared with their siblings
      (M = 31.9 nM, SD = 27.7), according to a paired samples t-test (P = 0.013). The
      difference was - most likely - not only accounted for by a difference in season
      of birth between ASD and non-ASD siblings since the mean 25(OH)D levels differed
      with similar effect size between the sibling pairs born during winter and summer,
      respectively. All children with African/Middle East background, both the children
      with ASD and their non-ASD siblings, had vitamin D deficiency. CONCLUSIONS: The
      findings suggest that low prenatal vitamin D may act as a risk factor for ASD,
      however, there is a need for replication with larger samples. Future research
      should study whether or not adequate supplementation of vitamin D to pregnant
      women might lower the risk for ASD in the offspring.

PMID- 25874077
TI  - Automated concept and relationship extraction for the semi-automated ontology
      management (SEAM) system.
AB  - BACKGROUND: We develop medical-specialty specific ontologies that contain the
      settled science and common term usage. We leverage current practices in
      information and relationship extraction to streamline the ontology development
      process. Our system combines different text types with information and
      relationship extraction techniques in a low overhead modifiable system. Our SEmi
      Automated ontology Maintenance (SEAM) system features a natural language
      processing pipeline for information extraction. Synonym and hierarchical groups
      are identified using corpus-based semantics and lexico-syntactic patterns. The
      semantic vectors we use are term frequency by inverse document frequency and
      context vectors. Clinical documents contain the terms we want in an ontology.
      They also contain idiosyncratic usage and are unlikely to contain the linguistic
      constructs associated with synonym and hierarchy identification. By including
      both clinical and biomedical texts, SEAM can recommend terms from those appearing
      in both document types. The set of recommended terms is then used to filter the
      synonyms and hierarchical relationships extracted from the biomedical corpus. We
      demonstrate the generality of the system across three use cases: ontologies for
      acute changes in mental status, Medically Unexplained Syndromes, and
      echocardiogram summary statements. RESULTS: Across the three uses cases, we held
      the number of recommended terms relatively constant by changing SEAM's
      parameters. Experts seem to find more than 300 recommended terms to be
      overwhelming. The approval rate of recommended terms increased as the number and
      specificity of clinical documents in the corpus increased. It was 60% when there
      were 199 clinical documents that were not specific to the ontology domain and 90%
      when there were 2879 documents very specific to the target domain. We found that
      fewer than 100 recommended synonym groups were also preferred. Approval rates for
      synonym recommendations remained low varying from 43% to 25% as the number of
      journal articles increased from 19 to 47. Overall the number of recommended
      hierarchical relationships was very low although approval was good. It varied
      between 67% and 31%. CONCLUSION: SEAM produced a concise list of recommended
      clinical terms, synonyms and hierarchical relationships regardless of medical
      domain.

PMID- 25874076
TI  - Constrained spherical deconvolution-based tractography and tract-based spatial
      statistics show abnormal microstructural organization in Asperger syndrome.
AB  - BACKGROUND: The aim of this study was to investigate potential differences in
      neural structure in individuals with Asperger syndrome (AS), high-functioning
      individuals with autism spectrum disorder (ASD). The main symptoms of AS are
      severe impairments in social interactions and restricted or repetitive patterns
      of behaviors, interests or activities. METHODS: Diffusion weighted magnetic
      resonance imaging data were acquired for 14 adult males with AS and 19 age, sex
      and IQ-matched controls. Voxelwise group differences in fractional anisotropy
      (FA) were studied with tract-based spatial statistics (TBSS). Based on the
      results of TBSS, a tract-level comparison was performed with constrained
      spherical deconvolution (CSD)-based tractography, which is able to detect complex
      (for example, crossing) fiber configurations. In addition, to investigate the
      relationship between the microstructural changes and the severity of symptoms, we
      looked for correlations between FA and the Autism Spectrum Quotient (AQ), Empathy
      Quotient and Systemizing Quotient. RESULTS: TBSS revealed widely distributed
      local increases in FA bilaterally in individuals with AS, most prominent in the
      temporal part of the superior longitudinal fasciculus, corticospinal tract,
      splenium of corpus callosum, anterior thalamic radiation, inferior fronto
      occipital fasciculus (IFO), posterior thalamic radiation, uncinate fasciculus and
      inferior longitudinal fasciculus (ILF). CSD-based tractography also showed
      increases in the FA in multiple tracts. However, only the difference in the left
      ILF was significant after a Bonferroni correction. These results were not
      explained by the complexity of microstructural organization, measured using the
      planar diffusion coefficient. In addition, we found a correlation between AQ and
      FA in the right IFO in the whole group. CONCLUSIONS: Our results suggest that
      there are local and tract-level abnormalities in white matter (WM) microstructure
      in our homogenous and carefully characterized group of adults with AS, most
      prominent in the left ILF.

PMID- 25874078
TI  - Identification of the orphan gene Prod 1 in basal and other salamander families.
AB  - BACKGROUND: The urodele amphibians (salamanders) are the only adult tetrapods
      able to regenerate the limb. It is unclear if this is an ancestral property that
      is retained in salamanders but lost in other tetrapods or if it evolved in
      salamanders. The three-finger protein Prod 1 is implicated in the mechanism of
      newt limb regeneration, and no orthologs have been found in other vertebrates,
      thus providing evidence for the second viewpoint. It has also been suggested that
      this protein could play a role in salamander-specific aspects of limb
      development. There are ten families of extant salamanders, and Prod 1 has only
      been identified in two of them to date. It is important to determine if it is
      present in other families and, particularly, the basal group of two families
      which diverged approximately 200 MYA. FINDINGS: We have used polymerase chain
      reaction (PCR) to identify Prod 1 in a Chinese hynobiid species Batrachuperus
      longdongensis. We obtained an intestinal transcriptome of the plethodontid
      Aneides lugubris and, from this, identified a primer which allowed PCR of two
      Prod 1 genes from this species. All known Prod 1 sequences from nine species in
      four families have been aligned, and a phylogenetic tree has been derived.
      CONCLUSIONS: Prod 1 is found in basal salamanders of the family Hynobiidae, and
      in at least three other families, so it may be present in all extant salamanders.
      It remains a plausible candidate to have been involved in the origins of limb
      regeneration, as well as the apomorphic aspects of limb development.

PMID- 25874079
TI  - In the digital world of the EMR, Open Notes change everything.
AB  - EMR use during medical visits has been found to distract physicians and
      negatively influence their ability to deliver patient-centered care. In this
      issue, Assis-Hassid and colleagues propose a redress of this effect by creating a
      23-item inventory of communication-related best practices regarding EMR use
      during medical visits with relevance for medical student training and enhanced
      clinical practice. This paper and recent initiatives to share physicians' EMR
      notes with patients through secure portals raise questions regarding the future
      role of the EMR and its implication for the patient-physician relationship. The
      purpose of this commentary is to provide a perspective on the EMR as part of the
      rapidly evolving digital environment and to discuss how the growing movement to
      provide patients full access to their EMR can act as a catalyst for the forging
      of a new model of patient-physician collaboration and partnership. 

PMID- 25874081
TI  - Vitamin D: something new under the sun.

PMID- 25309731
TI  - An evolutionarily significant unicellular strategy in response to starvation in
      Dictyostelium social amoebae.
AB  - The social amoeba Dictyostelium discoideum is widely studied for its
      multicellular development program as a response to starvation. Aggregates of up
      to 10 (6) cells form fruiting bodies containing (i) dormant spores (~80%) that
      can persist for months in the absence of nutrients, and (ii) dead stalk cells
      (~20%) that promote the dispersion of the spores towards nutrient-rich areas. It
      is often overlooked that not all cells aggregate upon starvation. Using a new
      quantitative approach based on time-lapse fluorescence microscopy and a low ratio
      of reporting cells, we have quantified this fraction of non-aggregating cells. In
      realistic starvation conditions, up to 15% of cells do not aggregate, which makes
      this third cell fate a significant component of the population-level response of
      social amoebae to starvation. Non-aggregating cells have an advantage over cells
      in aggregates since they resume growth earlier upon arrival of new nutrients, but
      have a shorter lifespan under prolonged starvation. We find that phenotypic
      heterogeneities linked to cell nutritional state bias the representation of cells
      in the aggregating vs. non-aggregating fractions, and thus affect population
      partitioning. Next, we report that the fraction of non-aggregating cells depends
      on genetic factors that regulate the timing of starvation, signal sensing
      efficiency and aggregation efficiency. In addition, interactions between clones
      in mixtures of non-isogenic cells affect the partitioning of each clone into both
      fractions. We further build a numerical model to test the evolutionary
      significance of the non-aggregating cell fraction. The partitioning of cells into
      aggregating and non-aggregating fractions is optimal in fluctuating environments
      with an unpredictable duration of starvation periods. Our study highlights the
      unicellular component of the response of social amoebae to starvation, and thus
      extends its evolutionary and ecological framework. 

PMID- 25874082
TI  - Hypercalcemic crisis induced by calcium carbonate.
AB  - We report a rare case of drug-induced hypercalcemic crisis in an elderly male
      resulting from calcium-containing supplements facilitated by thiazide diuretic
      and angiotensin-converting enzyme inhibitor. A 61-year-old male presented with
      hypercalcemic crisis along with renal insufficiency and metabolic alkalosis,
      mimicking the 'calcium-alkali syndrome'. The patient responded to aggressive
      intravenous hydration along with emergent hemodialysis and salmon calcitonin. He
      did not have hyperparathyroidism or malignancy. History revealed an average daily
      intake of only 1200 mg of calcium carbonate along with vitamin D 1000 U/day over
      an extended period of time. The patient completely recovered in 3 days and had
      normal serum calcium, parathyroid hormone and phosphorous level at 3-month follow
      up. The case highlights the life-threatening perils of indiscriminate and often
      excessive intake of calcium-containing supplements in an appropriate clinical
      setting. We also briefly discuss the epidemiology, clinical and laboratory
      features along with the recent advances in the understanding of the
      pathophysiology of calcium-alkali syndrome. 

PMID- 25874083
TI  - Intraglomerular micrometastasis of squamous cell carcinoma.
AB  - Intraglomerular metastasis is a rare manifestation of disseminated malignancies.
      We present here a case of intraglomerular metastatic carcinoma diagnosed as an
      incidental finding on a kidney biopsy in a 62-year-old male presenting with acute
      renal failure and metastatic penile squamous cell carcinoma. A proliferative
      lesion composed of highly atypical epithelial cells was found within a capillary
      loop and adjacent urinary space of an isolated glomerulus, which was
      immunoreactive for markers of squamous cell carcinoma. This case is a reminder
      that circulating cancer cells can occasionally lodge in glomeruli and appear as
      micrometastasis in kidney biopsies performed for the evaluation of renal
      dysfunction. 

PMID- 25874084
TI  - Long-term outcomes of survivors of ICU acute kidney injury requiring renal
      replacement therapy: a 10-year prospective cohort study.
AB  - BACKGROUND: Acute kidney injury (AKI) requiring renal replacement therapy (RRT)
      is associated with high in-hospital morbidity and mortality in critically ill
      patients. Long-term outcomes have received little attention. METHODS: The aim of
      this study was to characterize AKI-chronic kidney disease (CKD) nexus in
      critically ill patients with AKI (RIFLE class F). We performed a single-centre
      prospective observational study of 425 consecutive critically ill patients with
      AKI requiring RRT. None of these patients had pre-existing kidney disease.
      Primary outcomes were vital status and renal function at hospital discharge and
      at 5 and 10 years of follow-up. RESULTS: The overall in-hospital mortality of the
      study cohort was 47%, the mortality rates at 1, 5 and 10 years were 65, 75 and
      80%, respectively. At hospital discharge, recovery of renal function was complete
      in 56% of survivors. None of these patients developed CKD during follow-up.
      Ninety percent of the 100 survivors with partial recovery of renal function had
      ongoing CKD during long-term follow-up. CKD progressed to end-stage renal disease
      (ESRD) in 12 patients (3% of the cohort or 5% of survivors). The patients with
      post-AKICKD had a higher prevalence of hypertension, a higher rate of fatal
      cardiac diseases and a higher all-cause death rate. CONCLUSION: Long-term
      survival of critically ill patients with AKI requiring RRT is poor and determined
      by the development of de novo CKD. There is a need for close follow-up of
      patients surviving AKI to prevent progressive CKD and to reduce associated lethal
      cardiac events.

PMID- 25874085
TI  - Clinical and demographic predictors for vitamin D deficiency in multiethnic Asian
      patients with chronic kidney disease.
AB  - BACKGROUND: Vitamin D deficiency is common in patients with chronic kidney
      disease (CKD) and can cause skeletal and extraskeletal complications. The purpose
      of this study is to determine the clinical and demographic risk factors for
      vitamin D deficiency in multiethnic CKD patients in Singapore, a sun-rich
      country, so that patients at risk can be identified and treated early. METHODS:
      Pre-dialysis CKD patients from the National University Hospital (NUH), Singapore,
      Outpatient Renal Clinic who had their serum 25-hydroxyvitamin D [25(OH)D] levels
      measured between January 2008 and October 2010 were included. Their clinical and
      demographic parameters were collected from hospital databases and medical charts.
      Logistic regression was used to identify potential predictors for vitamin D
      deficiency in these patients. Two models, Mt30 and Mt16, were built using
      threshold serum 25(OH)D levels of <=30 and <16 ng/mL, respectively. RESULTS: Of
      the 219 patients included, 82.7 and 25.6% had serum 25(OH)D levels <=30 and <16
      ng/mL, respectively. Predictors identified for vitamin D deficiency include
      absence of vitamin D supplementation, type 2 diabetes mellitus (DM), non-cancer
      diagnosis, younger age, Malay race, treatment with calcitriol and higher serum
      bicarbonate (CO2) levels. Common predictors for the two models were lack of
      vitamin D supplementation and DM. The areas under the receiver-operating
      characteristic (ROC) curve for the validation sets were 0.697 and 0.687 for the
      Mt30 and Mt16 models, respectively. CONCLUSIONS: Vitamin D deficiency is common
      among multiethnic CKD patients in Singapore. Risk factors identified in this
      study include absence of vitamin D supplementation, DM, non-cancer diagnosis,
      young age, Malay race, calcitriol treatment and higher serum CO2. The knowledge
      of these risk factors is useful for predicting vitamin D deficiency in CKD
      patients in Singapore.

PMID- 25874086
TI  - Decreasing trends in incidence and prevalence of renal replacement therapy in
      Croatia from 2000 to 2009.
AB  - BACKGROUND: Recent studies have indicated stabilization in the incidence rates of
      renal replacement therapy (RRT) for end-stage renal disease (ESRD) in a number of
      European countries, the USA, and Japan. The aim of this study was to provide an
      update on the incidence and prevalence trends of RRT in Croatia over the past
      decade. METHODS: Data from the Croatian Registry of Renal Replacement therapy
      from 2000 to 2009 were analysed. Trends in incidence and prevalence were examined
      using the Poisson regression and Joinpoint regression analysis. RESULTS: The
      total adjusted incidence rate of RRT for ESRD increased from 106.1 per million
      population (pmp) in 2000 to 140.4 pmp in 2004, at annual percentage change (APC)
      7.0% [95% confidence interval (CI) 1.8, 12.6]. From 2004 to 2009, there was no
      rise in incidence [APC -1.0 (95% CI -4.5, 2.6)]. Continuous growth in incidence
      was present only in males [APC 2.6 (95% CI 0.9, 4.4)], in patients 65 years and
      older [APC 5.5 (95% CI 3.4, 7.6)], in patients with diabetes [APC 2.4 (95% CI
      0.5, 4.4)], hypertension/renovascular disease [APC 6.1 (95% CI 1.6, 10.8)] and
      unknown/missing diagnosis [APC13.8 (95% CI 9.0, 18.8)]. The total adjusted
      prevalence rate rose from 598.7 pmp in 2000 to 785.6 pmp in 2004, at an annual
      rise of 7.5% (95% CI 5.8, 9.3). In the 2004-09 period, the growth of RRT slowed
      to APC 2.4 (95% CI 1.2, 3.5), and reached 890.8 pmp in 2009. CONCLUSIONS: After a
      rapid increase in the incidence of RRT in Croatia from 2000 to 2004, the
      incidence rate has stabilized during the 2004-09 period. The stabilization of
      incidence is followed by a reduction in the growth in prevalence rate. The
      stabilization of RRT incidence could be attributed to the successful prevention
      and treatment of cardiovascular diseases that simultaneously improved renal
      survival.

PMID- 25874087
TI  - Relationship of missed and shortened hemodialysis treatments to hospitalization
      and mortality: observations from a US dialysis network.
AB  - BACKGROUND: The relationship of missed and shortened hemodialysis (HD) to
      clinical outcomes has not been well characterized in HD patients in the USA. Here
      we explored the frequency of missed and shortened treatments and their impact on
      mortality and hospitalization. METHODS: A retrospective review of data from a
      cohort of 15 340 HD patients treated in facilities operated by Dialysis Clinics,
      Inc. We compared the frequency of missed and shortened treatments by gender,
      race, age and treatment schedules [Mondays, Wednesdays, Fridays (MWF) versus
      Tuesdays, Thursdays, Saturdays (TTS)]. RESULTS: Of the 15 340 patients, 48% were
      non-Hispanic whites (NHWs), 41% African Americans (AAs), 6% Hispanics, 2% Native
      American (NA), 2% Asians and 1% other races. The median number of years on HD was
      1.8 years and the median follow-up was 12.4 months. The odds of missing at least
      one treatment in a month were higher in: patients aged <55 years, odds ratio (OR)
      1.33 (P<0.0001); in AAs, OR 1.51 (P < 0.0001); in NAs, OR 1.50 (P = 0.0003); and
      in Hispanics, OR 1.33 (P = 0.0003) compared with NHWs and in patients who
      dialyzed on TTS compared with MWF, OR 1.33 (P < 0.0001). Similar findings were
      observed for treatments shortened by at least 10 min per month. Missed and
      shortened treatments were most prevalent on Saturdays and were also associated
      with progressive increases in hospitalization and mortality. CONCLUSION: Missed
      and shortened HD treatments pose a challenge to providers. Improved adherence to
      prescribed dialysis may decrease the morbidity and mortality.

PMID- 25874088
TI  - Acute Epstein-Barr virus infection-associated collapsing glomerulopathy.
AB  - A 21-year-old woman presenting with acute Epstein-Barr virus (EBV) infection
      (infectious mononucleosis) was noted to have renal involvement. She had
      proteinuria, leukocyturia and microscopic hematuria, and 10 days after admission
      became nephrotic (23 g of protein per g of creatinine). Renal biopsy revealed
      glomerular tuft collapse, visceral epithelial cell proliferation and
      vacuolization consistent with collapsing glomerulopathy. She had only transient
      deterioration in renal function, attributed to contrast nephropathy, but after
      recovery remained proteinuric. Renal disease is well described in EBV infection,
      but collapsing glomerulopathy has not been reported previously. 

PMID- 25874089
TI  - Late onset tacrolimus-induced life-threatening polyneuropathy in a kidney
      transplant recipient patient.
AB  - A 59-year-old kidney recipient was diagnosed with a late onset of severe chronic
      inflammatory demyelinating polyradiculoneuropathy and almost fully recovered
      after stopping tacrolimus and one course of intravenous immunoglobulin treatment.
      Unique features of this patient are the unusually long time lapse between
      initiation of tacrolimus and the adverse effect (10 years), a strong causality
      link and several arguments pointing toward an inflammatory etiology. When facing
      new neurological signs and symptoms in graft recipients, it is important to bear
      in mind the possibility of a drug-induced adverse event. Discontinuation of the
      suspect drug and immunomodulation are useful treatment options. 

PMID- 25874090
TI  - Hypertension and a missing kidney.
AB  - Standard initial assessment via ultrasound of a 4-year-old girl with hypertension
      revealed the absence of one kidney. Instead of cross-sectional imaging of the
      retroperitoneal space, a functional (nuclear) study was performed. This revealed
      a malformed kidney within the chest. Though systemic levels of renin and
      aldosterone were not elevated, removal of the malformed kidney normalized the
      blood pressure. The presence of prominent smooth muscle nodules surrounding the
      arteries was seen in the malformed kidney. Initial attempts to avert surgery by
      pharmacologically reducing blood flow to the malformed kidney were unsuccessful.
      The review of the literature offers little evidence to support such a strategy. 

PMID- 25874091
TI  - Lanthanum, constipation, bafflying X-rays and a perforated colonic diverticulum.
AB  - Lanthanum carbonate (LC) is used as a phosphate binder in dialysed patients.
      Abdominal pain and constipation are known side effects of its use. Furthermore,
      in radiological studies, LC tablets are seen as intense radio-opaque deposits
      within the entire gastrointestinal tract-findings which can lead to diagnostic
      misinterpretations. An elderly patient on peritoneal dialysis and taking LC
      presented with peritonitis, secondary to a perforated colonic diverticulum. The
      possible association between the use of LC, worsening constipation and
      complications arising from colonic diverticular disease, are discussed. 

PMID- 25874092
TI  - Serum sickness following rabbit anti-thymocyte globulin for acute vascular renal
      allograft rejection.
AB  - A simultaneous pancreas-kidney transplant recipient developed serum sickness
      manifesting with severe upper limb allodynia, arthralgia and myalgia 17 days
      following rabbit anti-thymocyte globulin (rATG) infusion for biopsy-proven
      vascular rejection. Rapid resolution of symptoms followed treatment with high
      dose glucocorticoids. rATG is increasingly favoured over equine ATG in solid
      organ transplantation, and although rATG has a superior safety profile, it is
      important to maintain a high index of suspicion for serum sickness. 

PMID- 25874093
TI  - Promise and challenges of anticoagulation with dabigatran.
AB  - Dabigatran, marketed as Pradaxa (Boehringer Ingelheim) in the USA, is a direct
      thrombin inhibitor that holds great promise. It has been shown to reduce the risk
      of stroke and venous thromboembolism with similar if not greater efficacy than
      warfarin and with far fewer side effects. However, like other anticoagulants, it
      can cause severe bleeding complications and lacks a specific antidote with proven
      efficacy. The patient presented here was on dabigatran and sustained a traumatic
      intracranial hemorrhage (ICH). The ICH continued to progress despite prompt
      initiation of 3h of hemodialysis in an effort to remove the offending drug from
      the circulation. Through this case report, we highlight the challenges of
      anticoagulation with dabigatran including the lack of routine testing for
      monitoring its effect and of a specific antidote. We also discuss the potential
      role of dialysis in treating patients with life-threatening bleeding on
      dabigatran. 

PMID- 25874095
TI  - Reversible pulmonary hypertension in a kidney transplant with patent A-V fistula.
AB  - Pulmonary hypertension (PH) occurs in end-stage renal disease (ESRD) patients on
      long-term haemodialysis (HD) using an arterio-venous (A-V) access and can be
      attenuated by either kidney transplantation per se or surgical fistula
      ligation/revision. We report an exceptional case with severe PH after kidney
      transplantation due to ESRD and prior chronic intermittent HD via a patent A-V
      fistula. Gold-standard right heart catheterization findings have-for the first
      time-proven that following surgical shunt ligation of the A-V fistula,
      haemodynamics normalized completely in this patient. 

PMID- 25874094
TI  - The outcome of the primary vascular access and its translation into prevalent
      access use rates in chronic haemodialysis patients.
AB  - BACKGROUND: The American Fistula First Breakthrough Initiative currently aims for
      a 66% arterio-venous fistula (AVF) rate, while in the UK, best practice tariffs
      target AVF and arterio-venous graft (AVG) rates of 85%. The present study aims to
      assess whether these goals can be achieved. METHODS: We conducted a retrospective
      cohort study on patients who initiated haemodialysis from 1995 to 2006. Outcomes
      were the final failure-free survival of the first permanent access and the type
      of second access created. Prevalent use rates for the access types were
      calculated on the 1st January of each year for the second half of the study
      period. RESULTS: Two hundred and eleven out of 246 patients (86%) received an
      AVF, 16 (6%) an AVG and 19 (8%) a permanent catheter (PC) as the first permanent
      access. Eighty-six (35%) patients had final failure of the primary access. One-
      and 3-year final failure-free survival rates were 73 and 65% for AVF compared
      with 40 and 20% for AVG and 62 and 0% for PC, respectively. In patients with
      primary AVF, female sex {hazard ratio (HR) 2.20 [confidence interval (CI) 1.29
      3.73]} and vascular disease [HR 2.24 (CI 1.26-3.97)] were associated with a
      poorer outcome. A similar trend was observed for autoimmune disease [HR 2.14 (CI
      0.99-4.65)]. As second accesses AVF, AVG and PC were created in 47% (n = 40), 38%
      (n = 33) and 15% (n = 13). The median prevalent use rate was 80.5% for AVF, 14%
      for AVG and 5.5% for PC. CONCLUSIONS: The vascular access targets set by
      initiatives from the USA and UK are feasible in unselected haemodialysis
      patients. High primary AVF rates, the superior survival rates of AVFs even in
      patient groups at higher risk of access failure and the high rate of creation of
      secondary AVFs contributed to these promising results.

PMID- 25874096
TI  - Daptomycin for a complicated urinary tract infection with vancomycin-resistant
      Enterococcus faecium in a renal transplant recipient.
AB  - There is an increasing prevalence of urinary tract infection (UTI) caused by
      multiresistant gram-negative enteric bacilli such as extended-spectrum beta
      lactamase as well as Gram-positive enterococci whose vancomycin-resistance can be
      as high as 25%. We report on a 68-year-old Caucasian female with a UTI caused by
      a vancomycin-resistant Enterococcus faecium, only tested to be susceptible to
      gentamycin, linezolid and daptomycin. Within a day after administration of the
      bactericidal daptomycin clinical and laboratory signs of infection regressed and
      graft function recovered. Our case suggests that daptomycin might be an effective
      alternative for UTI caused by vancomycin-resistant enterococci. 

PMID- 25874097
TI  - Impact of chronic kidney disease on the natural history of alkaptonuria.
AB  - In alkaptonuria, deficiency of homogentisate 1,2-dioxygenase leads to the
      accumulation of homogentisic acid (HGA) and its metabolites in the body,
      resulting in ochronosis. Reports of patients with alkaptonuria who have decreased
      kidney function are rare, but this seems to play an important role in the natural
      history of the disease. We describe a 68-year-old female with chronic kidney
      disease (CKD) of unknown etiology who started peritoneal dialysis (PD) after 5
      years of follow-up and who was diagnosed with alkaptonuria at this time.
      Progressive exacerbation of ochronotic manifestations had been noted during these
      last few years, as kidney function worsened. After PD initiation, the disease
      continued to progress, and death occurred after one year and a half, due to
      severe aortic stenosis-related complications. Her 70-year-old sister was
      evaluated and also diagnosed with alkaptonuria. She had no renal dysfunction.
      Higher HGA excretion and significantly milder ochronosis than that of her sister
      were found. We present two alkaptonuric sisters with similar comorbidities except
      for the presence of CKD, who turned out to have totally different evolutions of
      their disease. This report confirms that kidney dysfunction may be an important
      factor in determining the natural history of alkaptonuria. 

PMID- 25874098
TI  - Acute pre-renal failure: acquired chloride diarrhea after bowel resection.
AB  - A 58-year old male with a history of small bowel resection and ileostomy
      presented with severe dehydration and high ostomy output. Laboratory
      investigation indicated hypochloremia, hypokalemia, hyponatremia, metabolic
      alkalosis, chloride-rich diarrhea, acute renal failure, and low urinary chloride
      excretion. Due to striking similarities to congenital chloridorrhea (CCD)
      reported in neonates, we empirically diagnosed acquired chloridorrhea (ACD,
      chloride diarrhea). This is a rare disorder resulting in profuse chloride-rich
      diarrhea and classic metabolic derangements affecting adults with chronic
      intestinal inflammation, often in association with bowel surgery. In this report,
      we review the relevant literature and discuss the genetic defects likely
      contributing to both the congenital and acquired forms of chloridorrhea. 

PMID- 25874099
TI  - Allograft dysfunction in a patient with an odd-looking kidney: case of renal
      lipomatosis and review of literature.
AB  - Renal lipomatosis was diagnosed in a kidney transplant recipient who presented
      with acute kidney injury (AKI) several years after transplantation. The patient
      had an odd-looking kidney transplant on ultrasound and computed tomography (CT)
      scan, showing a medullary mass with resultant compression of the surrounding
      renal parenchyma. A biopsy of the renal medulla confirmed fatty infiltration of
      the renal parenchyma. The patient underwent percutaneous nephrostomy and AKI
      resolved with relief of the obstruction. Renal lipomatosis is a rare condition
      that should be differentiated from other neoplasms of the kidney. When it occurs
      in a functioning transplant kidney, the treatment approach proves to be very
      challenging. 

PMID- 25874101
TI  - Tuberculosis, acute kidney injury and pancreatitis--what is the underlying cause?

PMID- 25874100
TI  - Hypertensive crisis precipitated by insulin-induced hypoglycemia with end-stage
      renal failure.

PMID- 25874102
TI  - Multifocal skeletal tuberculosis.

PMID- 25874103
TI  - Tuberculous pyomyositis in a renal transplant recipient.

PMID- 25874104
TI  - Kidney infiltration due to malignant lymphoma.

PMID- 25874105
TI  - Home remedies in peritoneal dialysis: genius or madness.

PMID- 25874106
TI  - Oral administration of Bifidobacterium longum in a gastro-resistant seamless
      capsule decreases serum phosphate levels in patients receiving haemodialysis.

PMID- 25874107
TI  - Effects of intermittent and continuous resistance training on proteinuria and
      hematuria in trained young women.

PMID- 25874108
TI  - Forty years on haemodialysis with the original arteriovenous fistula.

PMID- 25874109
TI  - Xylo-oligosaccharides and virginiamycin differentially modulate gut microbial
      composition in chickens.
AB  - BACKGROUND: The emergence and spread of antibiotic resistance in pathogens have
      led to a restriction on the use of antibiotic growth promoters (AGPs) in animal
      feed in some countries. The potential negative after-effects of a ban on AGPs
      could be mitigated by improving animal intestinal health with prebiotic dietary
      fibers such as xylo-oligosaccharides (XOS). However, the mechanism(s) by which an
      antibiotic or prebiotic contributes to the health and growth of animals are not
      well understood. Here, we evaluated XOS and virginiamycin (VIRG)-mediated changes
      in gut microbiota of broiler chickens using pyrosequencing of the 16S rRNA gene.
      RESULTS: There was a significant change in the relative abundance of certain
      bacteria, but the overall microbial diversity was not affected by treatment with
      either XOS or VIRG. Supplementation of HXOS (2 g XOS/kg diet) increased the
      proportion of Lactobacillus genus in the cecum, whereas Propionibacterium and
      Corynebacterium genera were enriched in the ileum of VIRG (16 mg/kg) treated
      birds. Furthermore, an increase in the cecal concentrations of acetate and
      propionate was observed in HXOS- and VIRG-fed chickens, respectively. These two
      groups of birds had better feed conversion efficiencies in comparison with the
      control group from day 7 to 21. In addition, temporal variations in the gut
      microbiota were evident in the chickens of different ages. CONCLUSIONS:
      Treatments with XOS or VIRG modified the relative abundance but not the presence
      or absence of specific microbial genus. The increase in both Lactobacillus spp.
      and acetate production in the cecum of HXOS-treated chickens may promote
      intestinal health.

PMID- 25874110
TI  - Non invasive ventilation as an additional tool for exercise training.
AB  - Recently, there has been increasing interest in the use of non invasive
      ventilation (NIV) to increase exercise capacity. In individuals with COPD, NIV
      during exercise reduces dyspnoea and increases exercise tolerance. Different
      modalities of mechanical ventilation have been used non-invasively as a tool to
      increase exercise tolerance in COPD, heart failure and lung and thoracic
      restrictive diseases. Inspiratory support provides symptomatic benefit by
      unloading the ventilatory muscles, whereas Continuous Positive Airway Pressure
      (CPAP) counterbalances the intrinsic positive end-expiratory pressure in COPD
      patients. Severe stable COPD patients undergoing home nocturnal NIV and daytime
      exercise training showed some benefits. Furthermore, it has been reported that in
      chronic hypercapnic COPD under long-term ventilatory support, NIV can also be
      administered during walking. Despite these results, the role of NIV as a routine
      component of pulmonary rehabilitation is still to be defined. 

PMID- 25874111
TI  - Does anxiety improve during weight restoration in anorexia nervosa? A systematic
      review.
AB  - Weight restoration is considered a principal outcome for treatment of Anorexia
      Nervosa (AN) due to the significant physiological disturbances resultant from
      acute states of malnutrition. Treatment outcomes for populations with AN are
      relatively poor, with increasing evidence suggesting that weight restoration
      alone is insufficient for long-term recovery. Research aimed at understanding the
      psychological sequaele of AN, in particular during weight restoration,
      nevertheless remain scarce. This systematic review aimed to evaluate existing
      research regarding anxiety symptoms during treatment for AN, and the relationship
      of anxiety symptomology and weight restoration. Twelve articles were identified
      from a systematic search of three electronic databases (PsycINFO, MEDLINE, and
      Web of Science), and were eligible for inclusion. Study methodology, results and
      quality were reviewed. Results regarding change in anxiety symptomology were
      inconsistent, though evidence did not support a relationship between anxiety
      change and weight restoration. Reasons for these inconsistencies and limitations
      of included studies were reviewed. Further research is warranted to elucidate the
      role of anxiety in AN and its implications for treatment and longer-term outcome.

PMID- 25874112
TI  - Treatments of medical complications of anorexia nervosa and bulimia nervosa.
AB  - Inherent to anorexia nervosa and bulimia nervosa are a plethora of medical
      complications which correlate with the severity of weight loss or the frequency
      and mode of purging. Yet, the encouraging fact is that most of these medical
      complications are treatable and reversible with definitive care and cessation of
      the eating-disordered behaviours. Herein, these treatments are described for both
      the medical complications of anorexia nervosa and those which are a result of
      bulimia nervosa. 

PMID- 25874113
TI  - Quality of MR thermometry during palliative MR-guided high-intensity focused
      ultrasound (MR-HIFU) treatment of bone metastases.
AB  - BACKGROUND: Magnetic resonance (MR)-guided high-intensity focused ultrasound has
      emerged as a clinical option for palliative treatment of painful bone metastases,
      with MR thermometry (MRT) used for treatment monitoring. In this study, the
      general image quality of the MRT was assessed in terms of signal-to-noise ratio
      (SNR) and apparent temperature variation. Also, MRT artifacts were scored for
      their occurrence and hampering of the treatment monitoring. METHODS: Analyses
      were performed on 224 MRT datasets retrieved from 13 treatments. The SNR was
      measured per voxel over time in magnitude images, in the target lesion and
      surrounding muscle, and was averaged per treatment. The standard deviation over
      time of the measured temperature per voxel in MRT images, in the muscle outside
      the heated region, was defined as the apparent temperature variation and was
      averaged per treatment. The scored MRT artifacts originated from the following
      sources: respiratory and non-respiratory time-varying field inhomogeneities,
      arterial ghosting, and patient motion by muscle contraction and by gross body
      movement. Distinction was made between lesion type, location, and procedural
      sedation and analgesic (PSA). RESULTS: The average SNR was highest in and around
      osteolytic lesions (21 in lesions, 27 in surrounding muscle, n = 4) and lowest in
      the upper body (9 in lesions, 16 in surrounding muscle, n = 4). The average
      apparent temperature variation was lowest in osteolytic lesions (1.2 degrees C, n
      = 4) and the highest in the upper body (1.7 degrees C, n = 4). Respiratory time
      varying field inhomogeneity MRT artifacts occurred in 85% of the datasets and
      hampered treatment monitoring in 81%. Non-respiratory time-varying field
      inhomogeneities and arterial ghosting MRT artifacts were most frequent (94% and
      95%) but occurred only locally. Patient motion artifacts were highly variable and
      occurred less in treatments of osteolytic lesions and using propofol and
      esketamine as PSA. CONCLUSIONS: In this study, the general image quality of MRT
      was observed to be higher in osteolytic lesions and lower in the upper body.
      Respiratory time-varying field inhomogeneity was the most prominent MRT artifact.
      Patient motion occurrence varied between treatments and seemed to be related to
      lesion type and type of PSA. Clinicians should be aware of these observed
      characteristics when interpreting MRT images.

PMID- 25874114
TI  - Analysis and visualisation of movement: an interdisciplinary review.
AB  - The processes that cause and influence movement are one of the main points of
      enquiry in movement ecology. However, ecology is not the only discipline
      interested in movement: a number of information sciences are specialising in
      analysis and visualisation of movement data. The recent explosion in availability
      and complexity of movement data has resulted in a call in ecology for new
      appropriate methods that would be able to take full advantage of the increasingly
      complex and growing data volume. One way in which this could be done is to form
      interdisciplinary collaborations between ecologists and experts from information
      sciences that analyse movement. In this paper we present an overview of new
      movement analysis and visualisation methodologies resulting from such an
      interdisciplinary research network: the European COST Action "MOVE - Knowledge
      Discovery from Moving Objects" (http://www.move-cost.info). This international
      network evolved over four years and brought together some 140 researchers from
      different disciplines: those that collect movement data (out of which the
      movement ecology was the largest represented group) and those that specialise in
      developing methods for analysis and visualisation of such data (represented in
      MOVE by computational geometry, geographic information science, visualisation and
      visual analytics). We present MOVE achievements and at the same time put them in
      ecological context by exploring relevant ecological themes to which MOVE studies
      do or potentially could contribute. 

PMID- 25874115
TI  - The impact of unilateral or bilateral cataract surgery on visual acuity and life
      quality of elderly patients.
AB  - In the current study, the CLVQOL was used to assess VRQOL before unilateral or
      bilateral cataract surgery and at the end of the follow-up period in order to
      determine the greater beneficial mode of surgery for patients, if one of the two
      surgical methods is more beneficial over the other. The patients were classified
      as receiving unilateral (group A) and bilateral cataract surgery (group B). There
      were no significant differences between groups A and B before the operation in
      terms of life quality scores, binocular weighted average LogMAR BCVA, age,
      educational level, gender, systematic and ocular comorbidities, and the
      complications of the operation. It was shown that visual acuity improved more
      significantly with bilateral cataract surgery than with unilateral surgery in
      elderly patients with a high preoperative disease burden in Shanghai city.
      However, the improvement in life quality was not different in patients receiving
      either bilateral or unilateral cataract surgery. 

PMID- 25874116
TI  - Safety and Visual Outcome of Visian Toric ICL Implantation after Corneal Collagen
      Cross-Linking in Keratoconus: Up to 2 Years of Follow-Up.
AB  - Purpose. To evaluate the long-term safety and clinical outcome of phakic Visian
      toric implantable collamer lens (ICL) insertion after corneal collagen cross
      linking (CXL) in progressive keratoconus. Methods. This was a retrospective study
      of 30 eyes (19 patients), with progressive keratoconus, who underwent sequential
      CXL followed by Visian toric ICL implantation after 6 months. Results. At
      baseline, 6 eyes had stage I, 14 eyes stage II, and 10 eyes stage III keratoconus
      graded by Amsler-Krumeich classification. At 6 months after CXL, only K (steep)
      and K (max) decreased significantly from baseline, with no change in visual
      acuity or refraction. Flattening in keratometric readings was stable thereafter.
      There was significant improvement in mean uncorrected distance visual acuity
      (1.57 +/- 0.56 to 0.17 +/- 0.06 logMAR, P < 0.001) and mean corrected distance
      visual acuity (0.17 +/- 0.08 to 0.11 +/- 0.05 logMAR, P < 0.001) at 12 months
      after ICL implantation that was maintained at the 2-year follow-up. Mean cylinder
      power and mean spherical equivalent (SE) also decreased significantly after ICL
      implantation. A small hyperopic shift in SE (+0.25 D) was observed at 2 years
      that did not alter visual outcomes. Conclusions. Visian toric ICL implantation
      following CXL is an effective option for improving visual acuity in patients with
      keratoconus up to 2 years. 

PMID- 25874117
TI  - Association between Ophthalmic Timolol and Hospitalisation for Bradycardia.
AB  - Introduction. Ophthalmic timolol, a topical nonselective beta-blocker, has the
      potential to be absorbed systemically which may cause adverse cardiovascular
      effects. This study was conducted to determine whether initiation of ophthalmic
      timolol was associated with an increased risk of hospitalisation for bradycardia.
      Materials and Methods. A self-controlled case-series study was undertaken in
      patients who were hospitalised for bradycardia and were exposed to timolol.
      Person-time after timolol initiation was partitioned into risk periods: 1-30
      days, 31-180 days, and >180 days. A 30-day risk period prior to initiating
      timolol was also included. All remaining time was considered unexposed. Results.
      There were 6,373 patients with at least one hospitalisation for bradycardia
      during the study period; 267 were exposed to timolol. Risk of bradycardia was
      significantly increased in the 31-180 days after timolol initiation (incidence
      rate ratio (IRR) = 1.93; 95% confidence interval (CI) 1.00-1.87). No increased
      risk was observed in the first 30 days or beyond 180 days of continuous exposure
      (IRR = 1.40; 95% CI 0.87-2.26 and IRR = 1.21; 95% CI 0.64-2.31, resp.).
      Conclusion. Bradycardia is a potential adverse event following timolol
      initiation. Practitioners should consider patient history before choosing a
      glaucoma regime and closely monitor patients after treatment initiation with
      topical nonselective beta-blocker eye drops. 

PMID- 25874118
TI  - Rate of corneal collagen crosslinking redo in private practice: risk factors and
      safety.
AB  - Objective. To report the rate of progression of keratectasia after primary
      crosslinking (CXL) and evaluate the safety and efficiency of CXL redo. Materials
      and Methods. We conducted a retrospective analysis of the patients who underwent
      CXL between 2010 and 2013 at the Beirut Eye Specialist Hospital, Lebanon.
      Progression of keratectasia was based on the presence of an increase in maximum
      keratometry of 1.00 D, a change in the map difference between two consecutive
      topographies of 1.00 D, a deterioration of visual acuity, or any change in the
      refraction. Primary and redo CXL were done using the same protocol. Results.
      Among the 221 eyes of 130 patients who underwent CXL, 7 eyes (3.17%) of five
      patients met the criteria of progression. All patients reported a history of
      allergic conjunctivitis and eye rubbing and progressed within 9 to 48 months. No
      complications were noted and all patients were stable 1 year after CXL redo.
      Conclusion. Allergic conjunctivitis and eye rubbing were the only risk factors
      associated with keratoconus progression after CXL. A close followup is thus
      mandatory, even years after the procedure. CXL redo seems to be a safe and
      efficient technique to halt the progression after a primary CXL. 

PMID- 25874119
TI  - Blending better beverage options: a nutrition education and experiential workshop
      for youths.
AB  - OBJECTIVE: To reduce intake of sugar-sweetened beverages (SSBs) in youths as a
      means to reduce obesity risk. METHODS: Youths 5-14 years old attending a summer
      program were given a two-hour workshop addressing the sugar content in SSBs, the
      health risks from drinking SSBs, and hands-on preparation as well as tastings of
      low-sugar beverage alternatives. Data on usual intake of SSBs was obtained at
      baseline, and pre- and postprogram surveys were conducted to gauge change in
      knowledge and/or attitudes regarding SSBs. RESULTS: There were 128 participants
      (63% male) in the program. SSBs were commonly consumed with over 80% reporting
      regular consumption (mean daily intake 17.9 ounces). Significant increase in
      knowledge regarding the sugar content of commonly consumed SSBs was achieved;
      however change in attitudes was not significant. The large majority of youths
      reported enjoying the workshop and intention to reduce intake of SSBs following
      program participation. CONCLUSION: SSBs are commonly consumed by youths.
      Knowledge regarding the sugar content of SSBs is easier to impart to youths than
      influencing attitudes held about these beverages. Long-term interventions that
      reach out to parents and address the widespread availability of SSBs are needed
      to influence resistant attitudes and beverage choosing behaviors in youths.

PMID- 25874120
TI  - Latino family childcare providers' beliefs, attitudes, and practices related to
      promotion of healthy behaviors among preschool children: a qualitative study.
AB  - BACKGROUND: The continuing rise of obesity among Latinos is a public health
      concern with an immediate need for early prevention. Changes in family structures
      have increased demand and reliance for child care for young children. Latino
      children are the fastest-growing segment of the child population in the United
      States, and research shows that Latino families use preschools and day care
      centers much less than those of other ethnic groups, apparently because of
      cultural preferences for family-like care. OBJECTIVES: Given that many low income
      Latino children attend family child care homes (FCCHs), there is a need to
      explore the role that FCCH providers may play in establishing and reinforcing
      children's early healthful eating and physical activity behaviors and
      consequently in the prevention of childhood obesity. DESIGN: Using purposive
      sampling, six focus groups were conducted in Spanish with licensed Latino FCCH
      providers (n = 44). Data was analyzed to identify recurrent themes. RESULTS:
      Latino FCCH providers described how they play an influential role in promoting
      healthful eating and physical activity behaviors of preschool children in their
      care. They also identified many barriers and challenges in establishing and
      maintaining healthful nutrition and physical activity behaviors, including high
      cost of healthy foods, cold weather, and physical environment of FCCH.
      CONCLUSIONS: Latino FCCH providers can have a strong impact in promoting
      healthful behaviors in low-income, Latino communities. They may be able to
      effectively deliver interventions targeting low-income, minority families to
      promote healthful eating and physical activity behaviors and prevent child
      obesity.

PMID- 25874121
TI  - Calorie labeling in a rural middle school influences food selection: findings
      from community-based participatory research.
AB  - BACKGROUND: Calorie labeling at the point-of-purchase in chain restaurants has
      been shown to reduce energy intake. OBJECTIVE: To investigate the impact of point
      of-purchase calorie information at one rural middle school. METHODS: With a
      community-based participatory research framework a mixed method approach was used
      to evaluate the impact of point-of-purchase calorie information. Students in
      grades 6-8, dining at the school cafeteria January and February 2010,
      participated for 17 school days each month; in January a menu was offered in the
      usual manner without calorie labels; the same menu was prepared in February with
      the addition of calorie labels at point-of-purchase. Gross calories served per
      student were measured each day allowing for matched comparison by menu. In
      March/April of 2010, 32 students who ate in the cafeteria 3 or more times per
      week were interviewed regarding their views on menu labeling. RESULTS: Calorie
      consumption decreased by an average of 47 calories/day; fat intake reduced by 2.1
      grams/day. Five main themes were consistent throughout the interviews.
      CONCLUSION: Point-of-purchase calorie labels can play a role in reducing the
      number of calories consumed by middle school age children at the lunch. The
      majority of students interviewed found the calorie labels helped them choose
      healthier food.

PMID- 25874122
TI  - Early life cognitive abilities and body weight: cross-sectional study of the
      association of inhibitory control, cognitive flexibility, and sustained attention
      with BMI percentiles in primary school children.
AB  - The objective of this study was to investigate the association of different
      cognitive abilities with children's body weight adjusted for further weight
      influencing sociodemographic, family, and lifestyle factors. Cross-sectional data
      of 498 primary school children (7.0 +/- 0.6 years; 49.8% boys) participating in a
      health promotion programme in southwest Germany were used. Children performed a
      computer-based test battery (KiTAP) including an inhibitory control task (Go-Nogo
      paradigm), a cognitive flexibility task, and a sustained attention task. Height
      and weight were measured in a standardized manner and converted to BMI
      percentiles based on national standards. Sociodemographic features (migration
      background and parental education), family characteristics (parental body
      weight), and children's lifestyle (TV consumption, physical activity, consumption
      of sugar-sweetened beverages and breakfast habits) were assessed via parental
      questionnaire. A hierarchical regression analysis revealed inhibitory control and
      cognitive flexibility to be significant cognitive predictors for children's body
      weight. There was no association concerning sustained attention. The findings
      suggest that especially cognitive abilities known as executive functions
      (inhibitory control and cognitive flexibility) are associated with children's
      body weight. Future longitudinal and intervention studies are necessary to
      investigate the directionality of the association and the potential of
      integrating cognitive training in obesity prevention strategies. This trial is
      registered with ClinicalTrials.gov DRKS00000494. 

PMID- 25874123
TI  - Associations of parental influences with physical activity and screen time among
      young children: a systematic review.
AB  - Parents play a critical role in developing and shaping their children's physical
      activity (PA) and sedentary behaviours, particularly in the early years of life.
      The aim of this systematic review is to identify current literature investigating
      associations of parental influences with both PA and screen time in young
      children. This systematic review was conducted in November 2013 using 6
      electronic databases covering research literature from January 1998 to November
      2013. Thirty articles that met inclusion criteria were identified. These studies
      covered five important aspects of parenting: (1) parenting practices; (2)
      parents' role modelling; (3) parental perceptions of children's PA and screen
      viewing behaviours; (4) parental self-efficacy; and (5) general parenting style.
      Findings suggest that parents' encouragement and support can increase children's
      PA, and reducing parents' own screen time can lead to decreased child screen
      time. Improving parenting practices, parental self-efficacy or changing parenting
      style may also be promising approaches to increasing PA time and decreasing
      screen time of young children. 

PMID- 25874124
TI  - Prenatal stress due to a natural disaster predicts adiposity in childhood: the
      Iowa Flood Study.
AB  - Prenatal stress can affect lifelong physical growth, including increased obesity
      risk. However, human studies remain limited. Natural disasters provide models of
      independent stressors unrelated to confounding maternal characteristics. We
      assessed degree of objective hardship and subjective distress in women pregnant
      during severe flooding. At ages 2.5 and 4 years we assessed body mass index
      (BMI), subscapular plus triceps skinfolds (SS + TR, an index of total adiposity),
      and SS : TR ratio (an index of central adiposity) in their children (n = 106).
      Hierarchical regressions controlled first for several potential confounds.
      Controlling for these, flood exposure during early gestation predicted greater
      BMI increase from age 2.5 to 4, as well as total adiposity at 2.5. Greater
      maternal hardship and distress due to the floods, as well as other nonflood life
      events during pregnancy, independently predicted greater increase in total
      adiposity between 2.5 and 4 years. These results support the hypothesis that
      prenatal stress increases adiposity beginning in childhood and suggest that early
      gestation is a sensitive period. Results further highlight the additive effects
      of maternal objective and subjective stress, life events, and depression,
      emphasizing the importance of continued studies on multiple, detailed measures of
      maternal mental health and experience in pregnancy and child growth. 

PMID- 25874125
TI  - The intrauterine and nursing period is a window of susceptibility for development
      of obesity and intestinal tumorigenesis by a high fat diet in Min/+ mice as
      adults.
AB  - We studied how obesogenic conditions during various life periods affected obesity
      and intestinal tumorigenesis in adult C57BL/6J-Min (multiple intestinal
      neoplasia)/+ mice. The mice were given a 10% fat diet throughout life (negative
      control) or a 45% fat diet in utero, during nursing, during both in utero and
      nursing, during adult life, or during their whole life-span, and terminated at 11
      weeks for tumorigenesis (Min/+) or 23 weeks for obesogenic effect (wild-type).
      Body weight at 11 weeks was increased after a 45% fat diet during nursing, during
      both in utero and nursing, and throughout life, but had normalized at 23 weeks.
      In the glucose tolerance test, the early exposure to a 45% fat diet in utero,
      during nursing, or during both in utero and nursing, did not affect blood
      glucose, whereas a 45% fat diet given to adults or throughout life did. However,
      a 45% fat diet during nursing or during in utero and nursing increased the number
      of small intestinal tumors. So did exposures to a 45% fat diet in adult life or
      throughout life, but without increasing the tumor numbers further. The
      intrauterine and nursing period is a window of susceptibility for dietary fat
      induced obesity and intestinal tumor development. 

PMID- 25874127
TI  - Reducing Hispanic children's obesity risk factors in the first 1000 days of life:
      a qualitative analysis.
AB  - OBJECTIVES: Modifiable behaviors during the first 1000 days (conception age 24
      months) mediate Hispanic children's obesity disparities. We aimed to examine
      underlying reasons for early life obesity risk factors and identify potential
      early life intervention strategies. METHODS: We conducted 7 focus groups with 49
      Hispanic women who were pregnant or had children < age 24 months. Domains
      included influences on childhood obesity risk factors and future intervention
      ideas. We analyzed data with immersion-crystallization methods until no new
      themes emerged. RESULTS: Themes included coping with pregnancy may trump healthy
      eating and physical activity; early life weight gain is unrelated to later life
      obesity; fear of infant hunger drives bottle and early solids introduction;
      beliefs about infant taste promote early solids and sugary beverage introduction;
      and belief that screen time promotes infant development. Mothers identified
      physicians, nutritionists, and relatives as important health information sources
      and expressed interest in mobile technology and group or home visits for
      interventions. CONCLUSION: Opportunities exist in the first 1000 days to improve
      Hispanic mothers' understanding of the role of early life weight gain in
      childhood obesity and other obesity risk factors. Interventions that link health
      care and public health systems and include extended family may prevent obesity
      among Hispanic children.

PMID- 25874126
TI  - Birth weight, current anthropometric markers, and high sensitivity C-reactive
      protein in Brazilian school children.
AB  - Studies have shown associations of birth weight with increased concentrations of
      high sensitivity C-reactive protein. This study assessed the relationship between
      birth weight, anthropometric and metabolic parameters during childhood, and high
      sensitivity C-reactive protein. A total of 612 Brazilian school children aged 5
      13 years were included in the study. High sensitivity C-reactive protein was
      measured by particle-enhanced immunonephelometry. Nutritional status was assessed
      by body mass index, waist circumference, and skinfolds. Total cholesterol and
      fractions, triglycerides, and glucose were measured by enzymatic methods. Insulin
      sensitivity was determined by the homeostasis model assessment method.
      Statistical analysis included chi-square test, General Linear Model, and General
      Linear Model for Gamma Distribution. Body mass index, waist circumference, and
      skinfolds were directly associated with birth weight (P < 0.001, P = 0.001, and P
      = 0.015, resp.). Large for gestational age children showed higher high
      sensitivity C-reactive protein levels (P < 0.001) than small for gestational age.
      High birth weight is associated with higher levels of high sensitivity C-reactive
      protein, body mass index, waist circumference, and skinfolds. Large for
      gestational age altered high sensitivity C-reactive protein and promoted
      additional risk factor for atherosclerosis in these school children, independent
      of current nutritional status. 

PMID- 25874128
TI  - Optic nerve sonography in the diagnostic evaluation of pseudopapilledema and
      raised intracranial pressure: a cross-sectional study.
AB  - Introduction. Differentiating pseudopapilledema from papilledema which is optic
      disk edema and a result of increased ICP (intracranial pressure) is important and
      can be done with noninvasive methods like orbital ultrasound examination. Method.
      This was a cross-sectional study in which patients with optic nerve head swelling
      were referred for LP exam after optic nerve head swelling diagnosis confirmation
      and having normal brain imaging (CT scan). Before LP (lumbar puncture) exam the
      patients were referred for optic nerve ultrasound test of both eyes. Results.
      Considering 5.7 mm as the upper limit for normal ONSD (optic nerve sheath
      diameter), sensitivity and negative predictive value of optic sonography in
      diagnosis of pseudopapilledema are 100% for both eyes. Calculated accuracy
      validity of ONSD measurement in detecting pseudopapilledema is 90% for the right
      eye and 87% for the left eye. Conclusion. Our study demonstrated a close
      correlation between optic nerve sheath dilation on ocular ultrasound and evidence
      of elevated ICP with optic disk swelling. With the aid of noninvasive diagnostic
      tests we can avoid unnecessary concerns along with expensive and invasive
      neurological investigations while targeting the correct diagnosis in bilateral
      optic disk swelling. Our study showed optic nerve sonography as a reliable
      diagnostic method for further usage. 

PMID- 25874129
TI  - Effect of pentoxifylline on microalbuminuria in diabetic patients: a randomized
      controlled trial.
AB  - Background. Pentoxifylline is a nonspecific phosphodiesterase inhibitor with anti
      inflammatory properties. Human studies have proved its antiproteinuric effect in
      patients with glomerular diseases, but this study was designed to assess the
      effects of add-on pentoxifylline to available treatment on reduction of
      microalbuminuria in diabetic patients without glomerular diseases. Methods. In a
      double-blind placebo-controlled, randomized study we evaluated the influence of
      pentoxifylline on microalbuminuria in type 2 diabetic patients. 40 diabetic
      patients with estimated glomerular filtration rate (eGFR) of more than 60
      mL/min/1.73 m(2) in eight weeks and microalbuminuria were randomized to two
      groups which will receive pentoxifylline 1200 mg/day or placebo added to regular
      medications for 6 months. albuminuria; eGFR was evaluated at three- and six-month
      follow-up period. Results. Baseline characteristics were similar between the two
      groups. At six months, the mean estimated GFR and albuminuria were not different
      between two groups at 3- and 6-month follow-up. Trend of albumin to creatinine
      ratio, systolic and diastolic blood pressure, and eGFR in both groups were
      decreased, but no significant differences were noted between two groups (P value
      > 0.05). Conclusion. Pentoxifylline has not a significant additive
      antimicroalbuminuric effect compared with placebo in patients with type 2
      diabetes with early stage of kidney disease; however, further clinical
      investigations are necessary to be done. 

PMID- 25874130
TI  - Clinicopathological correlation in asian patients with biopsy-proven lupus
      nephritis.
AB  - A total of 244 patients with lupus nephritis (219 women (89.8%) with a female to
      male ratio of 9 : 1) were included in the study. Clinical and laboratory findings
      at renal biopsy are clinically valuable in identifying different renal
      classifications of lupus pathology, activity, and chronicity index. Patients with
      class IVG had significantly higher proportions of microscopic hematuria,
      proteinuria, hypertension, impaired renal function, anemia, hypoalbuminuria, and
      positive anti-DNA antibody. All of these findings correlated well with high
      activity index and chronicity index of lupus pathology. Considering these
      correlations may help to determine the clinicopathologic status of lupus
      patients. 

PMID- 25874131
TI  - Comparing Two Types of Rabbit ATG prior to Reduced Intensity Conditioning
      Allogeneic Hematopoietic SCT for Hematologic Malignancies.
AB  - Different rabbit polyclonal antilymphocyte globulins (ATGs) are used in
      allogeneic hematopoietic stem cell transplantation (alloHSCT) to prevent graft
      versus-host disease (GvHD). We compared 2 different ATGs in alloHSCT after
      reduced intensity conditioning (RIC) for hematological malignancies. We reviewed
      30 alloHSCT for hematologic malignancies performed between 2007 and 2010 with
      fludarabine and i.v. busulfan as conditioning regimen. Patients alternatingly
      received Thymoglobulin or ATG-F. Median followup was 3.3 (2.5-4.5) years. Adverse
      events appeared to occur more frequently during Thymoglobulin infusion than
      during ATG-F infusion but without statistical significance (P = 0.14). There were
      also no differences in 3-year overall survival (OS), disease-free survival (DFS),
      relapse incidence, and transplant related mortality (TRM) in the Thymoglobulin
      versus ATG-F group: 45.7% versus 46.7%, 40% versus 33.7%, 40% versus 33.3%, and
      20% versus 33.3%. The same held for graft failure, rejection, infectious
      complications, immune reconstitution, and acute or chronic GvHD. In patients
      transplanted for hematologic malignancies after RIC, the use of Thymoglobulin is
      comparable to that of ATG-F in all the aspects evaluated in the study. However
      due to the small number of patients in each group we cannot exclude a possible
      difference that may exist. 

PMID- 25874132
TI  - Importance of genetic diversity assessment in crop plants and its recent
      advances: an overview of its analytical perspectives.
AB  - The importance of plant genetic diversity (PGD) is now being recognized as a
      specific area since exploding population with urbanization and decreasing
      cultivable lands are the critical factors contributing to food insecurity in
      developing world. Agricultural scientists realized that PGD can be captured and
      stored in the form of plant genetic resources (PGR) such as gene bank, DNA
      library, and so forth, in the biorepository which preserve genetic material for
      long period. However, conserved PGR must be utilized for crop improvement in
      order to meet future global challenges in relation to food and nutritional
      security. This paper comprehensively reviews four important areas; (i) the
      significance of plant genetic diversity (PGD) and PGR especially on
      agriculturally important crops (mostly field crops); (ii) risk associated with
      narrowing the genetic base of current commercial cultivars and climate change;
      (iii) analysis of existing PGD analytical methods in pregenomic and genomic era;
      and (iv) modern tools available for PGD analysis in postgenomic era. This
      discussion benefits the plant scientist community in order to use the new methods
      and technology for better and rapid assessment, for utilization of germplasm from
      gene banks to their applied breeding programs. With the advent of new
      biotechnological techniques, this process of genetic manipulation is now being
      accelerated and carried out with more precision (neglecting environmental
      effects) and fast-track manner than the classical breeding techniques. It is also
      to note that gene banks look into several issues in order to improve levels of
      germplasm distribution and its utilization, duplication of plant identity, and
      access to database, for prebreeding activities. Since plant breeding research and
      cultivar development are integral components of improving food production,
      therefore, availability of and access to diverse genetic sources will ensure that
      the global food production network becomes more sustainable. The pros and cons of
      the basic and advanced statistical tools available for measuring genetic
      diversity are briefly discussed and their source links (mostly) were provided to
      get easy access; thus, it improves the understanding of tools and its practical
      applicability to the researchers. 

PMID- 25874134
TI  - Recurrent febrile neutropenia and thrombocytopenia in a chronic cocaine user: a
      case of levamisole induced complications.
AB  - Cocaine is used by approximately 1.5 million Americans each month and up to 69%
      of the cocaine seized contains levamisole. The real incidence of cocaine
      levamisole induced neutropenia is unclear but probably underestimated. Associated
      complications include fever, thrombocytopenia, skin-vasculitis disorders, and
      rarely kidney injury. We present a young male, with chronic active cocaine use
      presenting with recurrent episodes of febrile neutropenia and thrombocytopenia.
      He underwent extensive work-up and was treated with many antibiotics and we
      suspect that his neutropenia and thrombocytopenia were caused by recurrent
      cocaine-levamisole use. 

PMID- 25874133
TI  - Unlimited Thirst for Genome Sequencing, Data Interpretation, and Database Usage
      in Genomic Era: The Road towards Fast-Track Crop Plant Improvement.
AB  - The number of sequenced crop genomes and associated genomic resources is growing
      rapidly with the advent of inexpensive next generation sequencing methods.
      Databases have become an integral part of all aspects of science research,
      including basic and applied plant and animal sciences. The importance of
      databases keeps increasing as the volume of datasets from direct and indirect
      genomics, as well as other omics approaches, keeps expanding in recent years. The
      databases and associated web portals provide at a minimum a uniform set of tools
      and automated analysis across a wide range of crop plant genomes. This paper
      reviews some basic terms and considerations in dealing with crop plant databases
      utilization in advancing genomic era. The utilization of databases for variation
      analysis with other comparative genomics tools, and data interpretation platforms
      are well described. The major focus of this review is to provide knowledge on
      platforms and databases for genome-based investigations of agriculturally
      important crop plants. The utilization of these databases in applied crop
      improvement program is still being achieved widely; otherwise, the end for
      sequencing is not far away. 

PMID- 25874135
TI  - Elastic band causing exfoliation of the upper permanent central incisors.
AB  - Objective. This study reports a case in which elastic band use culminated in the
      loss of the incisors. Case Report. An 11-year-old white girl was seen complaining
      of pain, with purulent discharge and severe tooth mobility. The bone destruction
      detected radiographically in the region, despite its single location and absence
      in posterior quadrants of the maxilla and/or mandible, was similar to that
      observed in Langerhans cell disease. To our surprise, an elastic band involving
      the midportion of the roots of the two upper central incisors was found during
      biopsy. The debris was removed and a metal wire was placed in permanent maxillary
      right and left incisors. The patient was followed up, but no improvement in tooth
      mobility was observed. Bone loss increased, and internal resorption and root
      exposure occurred, which culminated in the extraction of permanent maxillary
      right and left incisors. Conclusion. The present case highlights the fact that
      professionals sometimes are confronted by anamnestic reports never seen before. 

PMID- 25874136
TI  - Lipoid proteinosis: a rare encounter in dental office.
AB  - Lipoid proteinosis is a sporadic congenital metabolic disorder which is
      characterized by deposition of hyaline material in dermis, submucosal connective
      tissue, and various internal organs. It has an extremely low prevalence rate with
      less than 300 cases reported so far. This progressive disease has a vast spectrum
      of manifestations ranging from asymptomatic lesions to fatal seizures and
      respiratory obstruction making timely diagnosis of this rare disorder an
      imperative task for oral health care practitioners. We report a case of
      characteristic oral manifestations of lipoid proteinosis in a 28-year-old male
      patient along with a review of relevant prevailing literature. 

PMID- 25874137
TI  - An Atypical Case of Methemoglobinemia due to Self-Administered Benzocaine.
AB  - Acquired methemoglobinemia is an uncommon hemoglobinopathy that results from
      exposure to oxidizing agents, such as chemicals or medications. Although, as
      reported in the adult population, it happens most often due to prescribed
      medication or procedural anesthesia and not due to easily accessed over-the
      counter medications, the authors will describe an otherwise healthy male adult
      with no known medical history and no prescribed medications, who presented to the
      emergency department reporting generalized weakness, shortness of breath,
      headache, dizziness, and pale gray skin. In addition, the patient reported that
      he also had a severe toothache for several days, which he had been self-treating
      with an over-the-counter oral benzocaine gel. Ultimately, the diagnosis of
      methemoglobinemia was made by clinical history, physical examination, and the
      appearance of chocolate-colored blood and arterial blood gas (ABG) with
      cooximetry. After 2 mg/kg of intravenous methylene blue was administered, the
      patient had complete resolution of all signs and symptoms. This case illustrates
      that emergency physicians should be keenly aware of the potential of toxic
      hemoglobinopathy secondary to over-the-counter, nonprescribed medications.
      Discussion with patients regarding the dangers of inappropriate use of these
      medicines is imperative, as such warnings are typically not evident on product
      labels. 

PMID- 25874138
TI  - Acute Cholangitis following Intraductal Migration of Surgical Clips 10 Years
      after Laparoscopic Cholecystectomy.
AB  - Background. Laparoscopic cholecystectomy represents the gold standard approach
      for treatment of symptomatic gallstones. Surgery-associated complications include
      bleeding, bile duct injury, and retained stones. Migration of surgical clips
      after cholecystectomy is a rare complication and may result in gallstone
      formation "clip cholelithiasis". Case Report. We report a case of a 55-year-old
      female patient who presented with right upper quadrant pain and severe sepsis
      having undergone an uncomplicated laparoscopic cholecystectomy 10 years earlier.
      Computed tomography (CT) imaging revealed hyperdense material in the common bile
      duct (CBD) compatible with retained calculus. Endoscopic retrograde
      cholangiopancreatography (ERCP) revealed appearances in keeping with a migrated
      surgical clip within the CBD. Balloon trawl successfully extracted this,
      alleviating the patient's jaundice and sepsis. Conclusion. Intraductal clip
      migration is a rarely encountered complication after laparoscopic cholecystectomy
      which may lead to choledocholithiasis. Appropriate management requires timely
      identification and ERCP. 

PMID- 25874139
TI  - Osteogenesis imperfecta, pseudoachalasia, and gastric cancer.
AB  - Osteogenesis imperfecta (OI) is a rare, inherited skeletal disorder characterized
      by abnormalities of type 1 collagen. Malignancy is rarely reported in patients
      with OI and it was suggested that this disease can protect against cancer. Here,
      we report a 41-year-old woman with symptoms of achalasia where repeated treatment
      of pneumatic dilation and stent replacement was unsuccessful; therefore, surgery
      was performed. Pathology showed gastric adenocarcinoma unexpectedly. Chemotherapy
      was given after assessing dihydropyrimidine dehydrogenase (DPD) enzyme activity,
      which can be deficient in OI patients. This is the first report of gastric cancer
      mimicking achalasia in a patient with OI. 

PMID- 25874140
TI  - Hepatorenal syndrome with cirrhotic cardiomyopathy: case report and literature
      review.
AB  - The hepatorenal syndrome (HRS) is defined as a potentially reversible kidney
      failure in patients with cirrhosis and ascites. An association of HRS and
      cirrhotic cardiomyopathy has been reported recently, but there are no result
      studies about the use of positive inotropes as part of the acute phase treatment.
      We report the case of a patient diagnosed with HRS, with high levels of NT pro
      BNP, but with normal ejection fraction of the left ventricle, which showed
      abnormalities in systolic function through speckle tracking in echocardiography,
      reversible after the infusion of dobutamine. The patient showed clinical and
      laboratory improvement of his renal function after the infusion of dobutamine.
      Clinical studies are needed on HRS therapeutic approach taking into account the
      myocardial dysfunction as a major contributing factor to renal dysfunction. 

PMID- 25874141
TI  - Fever of unknown origin: an unusual presentation of kikuchi-fujimoto disease.
AB  - Kikuchi-Fujimoto disease is a rare, benign, and self-limiting condition that
      mostly affects young females. Cervical lymphadenopathy with fever is the most
      common presentation of the disease. It may have unusual presentations that can
      lead to diagnostic dilemma and delay in diagnosis. We report a case of a 25-year
      old female who presented with relapsing fever and cervical lymphadenopathy.
      Because of atypical presentation, there was a delay in diagnosis and increase in
      morbidity. High index of suspicion with collaboration between clinicians and
      pathologists is essential for early and accurate diagnosis of the disease. 

PMID- 25874142
TI  - Case report of a patient with left ventricular assistance device undergoing
      chemotherapy for a new diagnosis of lung cancer.
AB  - The optimal management of cancer in patients with severe heart failure is not
      defined. This issue is particularly challenging when a diagnosis of limited-stage
      small cell lung cancer (SCLC) is made incidentally in the context of evaluating
      patient for candidacy for cardiac transplantation. Limited-stage SCLC is
      typically managed on a curative therapeutic paradigm with combined modality
      approach involving chemotherapy and radiation. Even with excellent performance
      status and good organ function, the presence of severe cardiomyopathy poses
      significant challenges to the delivery of even single modality approach with
      chemotherapy or radiotherapy, let alone the typical curative combined modality
      approach. With mechanical left ventricular devices to provide cardiac support,
      treatment options for cancer in the setting of advanced heart failure may be
      improved. Here we discuss the therapeutic dilemma involving a patient with severe
      cardiomyopathy and left ventricular assistant device (LVAD) who was found to have
      limited-stage SCLC during the evaluation process for cardiac transplantation. 

PMID- 25874143
TI  - The Case of an Elderly Male Patient with Unknown Primary Mucinous Adenocarcinoma
      within Presacral Teratoma (Teratoma with Malignant Transformation).
AB  - Teratomas are rarely seen in adults, and presacral region is an area where they
      rarely settle in. Similarly, only about 1% of teratomas show malignant
      transformation. Malignant transformation is often associated with the area where
      teratoma settles in. Malignant transformation of mediastinal teratomas is more
      frequent than the ones located in retroperitoneal area and gonad. They most
      commonly show rhabdomyosarcoma, primitive neuroectodermal tumor, enteric
      adenocarcinoma, and leukemia transformation. In teratomas showing malignant
      transformation, the clinical course is aggressive; and survival of patients with
      metastatic disease is very low. The primary treatment of teratomas with malignant
      transformations is surgical. Effect of radiotherapy and chemotherapy is not clear
      in patients, to whom surgical operation cannot be applied, or those who are with
      residual tumor, even if surgical operation can be applied to them, or those who
      are at metastatic stage. In this paper, we presented a 76-year-old male patient
      due to the histologic diagnosis of mucinous adenocarcinoma within teratoma, in
      whom approximately 7 cm presacral mass was found during the radiographic
      examination made by the reason of low back pain and pelvic pain. 

PMID- 25874144
TI  - Metastasis of ciliary body melanoma to the contralateral eye: a case report and
      review of uveal melanoma literature.
AB  - Many types of cancers metastasize to the eye. However, uveal melanoma
      metastasizing to the contralateral choroid is very rare. We report the case of a
      68-year-old man with history of treated uveal melanoma of the right eye that
      developed metastasis to the liver and the choroid of the left eye. Ten years
      earlier, he was diagnosed to have uveal melanoma of the right eye and was
      initially treated with plaque radiotherapy. Two years later, upon progression of
      the disease in the right eye he had enucleation of the eye. We describe the
      patient's clinical history, the diagnosis of recurrent disease in the
      contralateral eye, therapy of the left eye, and systemic metastasis. In addition,
      we reviewed the published medical literature and described the recent advances in
      the management of uveal melanoma. 

PMID- 25874145
TI  - Long-Term Outcomes of Radial Keratotomy, Laser In Situ Keratomileusis, and
      Astigmatic Keratotomy Performed Consecutively over a Period of 21 Years.
AB  - Purpose. To describe a case of 3 refractive procedures performed in one eye over
      2 decades. Methods. CASE REPORT: Results. A 41-year-old patient presented for
      refractive surgery evaluation. His ocular history includes bilateral radial
      keratotomy performed 21 years ago for moderate myopia: spherical equivalence of 
      4.25 D bilaterally. Postoperative uncorrected visual acuity (UCVA) was 20/30;
      however, over time he developed a hyperopic shift and UCVA decreased to 20/40 in
      the right eye. Thus, laser-assisted in situ keratomileusis (LASIK) was performed
      at an outside institution 6.5 years later, and the patient had initial
      improvement of UCVA to 20/25. Due to a change in refractive error, the patient
      underwent uneventful astigmatic keratotomy 13 years after LASIK in the right eye,
      and 1.5 years after surgery best-corrected visual acuity was 20/25 with manifest
      refraction of -1.00 + 5.50 * 134 degrees .  Conclusion. We report the outcomes
      and natural refractive progression in a patient who underwent three corneal
      refractive procedures over two decades. This case underlines the difficulties of
      long-term management of post-RK hyperopia and astigmatism.

PMID- 25874146
TI  - Irreducible dislocation of the great toe interphalangeal joint secondary to an
      incarcerated sesamoid.
AB  - Irreducible dorsal dislocation of the interphalangeal (IP) joint of the great toe
      is rare. We report a case of a 29-year-old gentleman who presented to the
      Orthopaedic Surgery Specialist Outpatient Clinic with an irreducible IP joint of
      the great toe that had been untreated for 4 weeks. The mechanism of injury is
      believed to be a combination of axial loading with a hyperdorsiflexion force when
      the patient fell foot first into a drain. As the patient did not report severe
      symptoms and a true lateral radiograph was not ordered, the dislocation was
      missed initially at the emergency department. The patient had continued to run
      and play field hockey prior to visiting us. Incarceration of the sesamoid became
      a block to manipulation and reduction at the specialist outpatient clinic 3 weeks
      later. The patient was treated with open surgical exploration, resection of the
      interposed sesamoid, and Kirschner-wire fixation of the IP joint followed by
      occupational therapy for mobilization exercises. The operative course was
      uneventful. At 6 months after surgery, the patient could walk, run, and return to
      sports. 

PMID- 25874147
TI  - Traumatic hip dislocation with associated femoral head fracture.
AB  - Dislocation of the hip is a critical injury that results from high-energy trauma.
      This paper describes a case of posterior dislocation of the right hip in a 35
      year-old woman with associated ipsilateral femoral head fracture. Initial
      treatment included reduction of the right hip through posterior approach and
      fixation of the femoral head fracture with three absorbable screws. After 15
      month follow-up, a full range of motion has been achieved and there are no signs
      of avascular necrosis, hip instability, or limping. The authors describe their
      method of surgery. 

PMID- 25874148
TI  - Endoscopic endonasal approach of congenital meningoencephalocele surgery: first
      reported case in lithuania.
AB  - Meningoencephalocele is a rare condition that usually occurs in children and is
      treated by neurosurgeons with occasional help from ENT doctors. The symptoms of
      meningoencephalocele might not develop until adulthood, but usually they are
      apparent immediately after birth. The case of small anterior basal transethmoidal
      meningoencephalocele in a 24-year-old patient who had headaches and runny nose
      since childhood is presented. Endonasal endoscopic approach for
      meningoencephalocele removal and skull base defect reconstruction was used. It
      was concluded that endoscopic endonasal approach is less invasive and provides an
      acceptable operative outcome with short recovery time and less postoperative
      complications in comparison with other external microsurgical approaches. 

PMID- 25874149
TI  - Treatment for retinopathy of prematurity in an infant with adenoviral
      conjunctivitis.
AB  - Retinopathy of prematurity (ROP) has been a major problematic disorder during
      childhood. Laser photocoagulation (LPC) has been proven to be effective in most
      of the ROP cases. Adenoviral conjunctivitis (AVC) is responsible for epidemics
      among adult and pediatric population. It has also been reported to be a cause of
      outbreaks in neonatal intensive care units (NICU) several times. We herein
      demonstrate a case with AVC who underwent LPC for ROP. And we discuss the
      treatment methodology in such cases. 

PMID- 25874150
TI  - Primary antiphospholipid syndrome associated with pneumonia: a case report of a
      16-year-old male patient.
AB  - Antiphospholipid syndrome (APS) is an autoimmune disease characterised by
      arterial and/or venous thrombosis and/or recurrent pregnancy loss in the presence
      of antiphospholipid (APL) antibodies. It is evaluated as APS when it develops
      associated with other systemic autoimmune diseases or primary APS if there is no
      concomitant disorder. In this study, we present a case of a 16-year-old male
      patient with primary APS. The patient was admitted with presumptive diagnosis of
      pneumonia, but multiple pulmonary thromboembolism (PTE) was observed on
      computerized tomography (CT) pulmonary angiography. APL antibodies positivity and
      thrombocytopenia developed in our patient. The patient was evaluated as primary
      APS since another etiology that could explain PTE was not found. Primary APS is a
      rare disease in children along with adolescents, compared with APS associated
      with other systemic autoimmune diseases. We present here a young male patient
      with primary APS and PTE to contribute to the literature. The patient initially
      had pneumonia but later developed PTE and thrombocytopenia. 

PMID- 25874151
TI  - Transarterial coil embolization of a symptomatic posttraumatic plantar
      pseudoaneurysm.
AB  - Posttraumatic pseudoaneurysms of the lateral plantar artery are rare. We report
      the case of a 31-year-old woman with a painful pseudoaneurysm of the lateral
      plantar artery resulting from a deep plantar cut injury. The pseudoaneurysm was
      successfully treated by performing a transarterial "frontdoor-backdoor" coil
      embolization technique, which is a minimally invasive alternative to conventional
      ligature of the artery. 

PMID- 25874152
TI  - A primary retroperitoneal mucinous tumor.
AB  - A twenty-five-year-old female presented with a large retroperitoneal mass. Workup
      included history and physical exam, imaging, biopsy, colonoscopy, and gynecologic
      exam. After surgical resection, the mass was determined to be a primary
      retroperitoneal mucinous tumor (PRMT). Clinically and histologically, these
      tumors are similar pancreatic and ovarian mucinous neoplasms. PRMTs are rare and
      few case reports have been published. PRMTs are divided into mucinous
      cystadenomas, mucinous borderline tumors of low malignant potential, and mucinous
      carcinoma. These tumors have malignant potential so resection is indicated and in
      some cases adjuvant chemotherapy and/or surveillance imaging. 

PMID- 25874153
TI  - Intramyocardial Dissection following Postinfarction Ventricular Wall Rupture
      Contained by Surrounding Postoperative Adhesions.
AB  - Introduction. Dissection of the myocardium is a rare form of cardiac rupture,
      caused by a hemorrhagic dissection among the spiral myocardial fibers, its
      diagnosis is rarely established before the operation or death, and extremely few
      cases have been reported in the literature and none of these cases seem to have a
      history of previous cardiac surgery which makes our report unique. Case
      Presentation. A 61-year-old female patient was admitted into the emergency room
      with complaints of progressive chest pain for 2 days. She had a history of second
      time prosthetic aortic valve replacement and was under anticoagulation therapy.
      She was diagnosed with an acute inferoposterior myocardial infarction and
      underwent emergency coronary angiography revealing spontaneous recanalization of
      the right coronary artery. During the follow-up, she developed cardiogenic shock
      and a new occurring systolic ejection murmur. Transthoracic echocardiography
      showed a left ventricular free wall rupture; then, she was taken in for emergency
      surgery. During the operation, a rupture zone and a wide intramyocardial
      dissecting area were detected. Intraventricular patch repair technic with
      autologous pericardial patch was used to exclude the ruptured area. Following the
      warming period, despite adequate hemostasis, hemorrhage around suture lines
      progressively increased, leading to the patient's death. Conclusion. Pericardial
      adhesions might contain left ventricular rupture leading to intramyocardial
      dissection. 

PMID- 25874155
TI  - Corrigendum to "Antitumor Molecular Mechanism of Chlorogenic Acid on Inducting
      Genes GSK-3beta and APC and Inhibiting Gene beta-Catenin".
AB  - [This corrects the article DOI: 10.1155/2013/951319.]. 

PMID- 25874154
TI  - Type 1 diabetes and osteoporosis: from molecular pathways to bone phenotype.
AB  - The link between type 1 diabetes mellitus (DM1) and osteoporosis, identified
      decades ago, has gained attention in recent years. While a number of cellular
      mechanisms have been postulated to mediate this association, it is now
      established that defects in osteoblast differentiation and activity are the main
      culprits underlying bone fragility in DM1. Other contributing factors include an
      accumulation of advanced glycation end products (AGEs) and the development of
      diabetes complications (such as neuropathy and hypoglycemia), which cause further
      decline in bone mineral density (BMD), worsening geometric properties within
      bone, and increased fall risk. As a result, patients with DM1 have a 6.9-fold
      increased incidence of hip fracture compared to controls. Despite this increased
      fracture risk, bone fragility remains an underappreciated complication of DM1 and
      is not addressed in most diabetes guidelines. There is also a lack of data
      regarding the efficacy of therapeutic strategies to treat osteoporosis in this
      patient population. Together, our current understanding of bone fragility in DM1
      calls for an update of diabetes guidelines, better screening tools, and further
      research into the use of therapeutic strategies in this patient population. 

PMID- 25874156
TI  - Generalizing thermodynamic properties of bulk single-walled carbon nanotubes.
AB  - The enthalpy and Gibbs free energy thermodynamical potentials of single walled
      carbon nanotubes were studied of all types (armchairs, zig-zags, chirals (n>m),
      and chiral (n<m)). Bulk values of these thermodynamic potentials were obtained
      using a previously demonstrated robust method based on semi-empirical PM3
      calculations and an extrapolated cluster approach. Those values were used to
      study the relationship between the thermodynamic potentials and the diameter of
      the nanotube. Results of this study led to the proposal of a single equation for
      the thermodynamical potential of [Formula: see text] or [Formula: see text]
      (assembly of nanotubes from atoms) versus the chiral vector indexes n and m for
      any given nanotube. The equations show a good level of accuracy in predicting
      thermodynamic potentials for practical applications.

PMID- 25874157
TI  - Autoinhibitory mechanisms of ERG studied by molecular dynamics simulations.
AB  - ERG, an ETS-family transcription factor, acts as a regulator of differentiation
      of early hematopoietic cells. It contains an autoinhibitory domain, which
      negatively regulates DNA-binding. The mechanism of autoinhibitory is still
      illusive. To understand the mechanism, we study the dynamical properties of ERG
      protein by molecular dynamics simulations. These simulations suggest that DNA
      binding autoinhibition associates with the internal dynamics of ERG.
      Specifically, we find that (1), The N-C terminal correlation in the inhibited ERG
      is larger than that in uninhibited ERG that contributes to the autoinhibition of
      DNA-binding. (2), DNA-binding changes the property of the N-C terminal
      correlation from being anti-correlated to correlated, that is, changing the
      relative direction of the correlated motions and (3), For the Ets-domain
      specifically, the inhibited and uninhibited forms exhibit essentially the same
      dynamics, but the binding of the DNA decreases the fluctuation of the Ets-domain.
      We also find from PCA analysis that the three systems, even with quite different
      dynamics, do have highly similar free energy surfaces, indicating that they share
      similar conformations.

PMID- 25874158
TI  - Investigation of CuGaSe2/CuInSe2 double heterojunction interfaces grown by
      molecular beam epitaxy.
AB  - In-situ reflection high-energy electron diffraction (RHEED) observation and X-ray
      diffraction measurements were performed on heterojunction interfaces of
      CuGaSe2/CnInSe2/CuGaSe2 grown on GaAs (001) using migration-enhanced epitaxy. The
      streaky RHEED pattern and persistent RHEED intensity oscillations caused by the
      alternate deposition of migration-enhanced epitaxy sequence are observed and the
      growths of smooth surfaces are confirmed. RHEED observation results also
      confirmed constituent material interdiffusion at the heterointerface. Cross
      sectional transmission electron microscopy showed a flat and abrupt
      heterointerface when the substrate temperature is as low as 400  degrees C. These
      have been confirmed even by X-ray diffraction and photoluminescence measurements.

PMID- 25874159
TI  - Novel type-II material system for laser applications in the near-infrared regime.
AB  - The design and experimental realization of a type-II "W"-multiple quantum well
      heterostructure for emission in the lambda > 1.2 MUm range is presented. The
      experimental photoluminescence spectra for different excitation intensities are
      analyzed using microscopic quantum theory. On the basis of the good theory
      experiment agreement, the gain properties of the system are computed using the
      semiconductor Bloch equations. Gain values comparable to those of type-I systems
      are obtained.

PMID- 25874161
TI  - Pain in multiple system atrophy and progressive supranuclear palsy compared to
      Parkinson's disease.
AB  - BACKGROUND: Pain is a common nonmotor symptom in Parkinson's disease (PD). The
      pathophysiology of pain in PD is not well understood. Pain characteristics have
      rarely been studied in atypical parkinsonian disorders such as Multiple System
      Atrophy (MSA) and Progressive Supranuclear Palsy (PSP). AIM OF THE STUDY: We
      aimed to evaluate pain intensity, location, and associated symptoms in atypical
      parkinsonian disorders compared to PD. METHODS: Twenty-one patients with MSA, 16
      patients with PSP, and 65 patients with PD were screened for pain using question
      1.9 of the MDS-UPDRS. Pain intensity was quantified using the short form McGill
      Pain Questionnaire (SFMPQ). Pain locations were documented. Motor disability was
      measured using UPDRS-III. Affective symptoms were assessed using the Hospital
      Anxiety and Depression Scale (HADS). RESULTS: Pain was significantly more common
      and more severe in PD and MSA compared to PSP (P < 0.01). Pain locations were
      similar with limb pain being the most common followed by neck and back pain. Pain
      intensity correlated with HADS scores but not motor severity. CONCLUSIONS: Pain
      is more common and more intense in PD and MSA than PSP. Differences in
      distribution of neurodegenerative pathologies may underlie these differential
      pain profiles.

PMID- 25874160
TI  - Non-descanned multifocal multiphoton microscopy with a multianode photomultiplier
      tube.
AB  - Multifocal multiphoton microscopy (MMM) improves imaging speed over a point
      scanning approach by parallelizing the excitation process. Early versions of MMM
      relied on imaging detectors to record emission signals from multiple foci
      simultaneously. For many turbid biological specimens, the scattering of emission
      photons results in blurred images and degrades the signal-to-noise ratio (SNR).
      We have recently demonstrated that a multianode photomultiplier tube (MAPMT)
      placed in a descanned configuration can effectively collect scattered emission
      photons from each focus into their corresponding anodes significantly improving
      image SNR for highly scattering specimens. Unfortunately, a descanned MMM has a
      longer detection path resulting in substantial emission photon loss. Optical
      design constraints in a descanned geometry further results in significant optical
      aberrations especially for large field-of-view (FOV), high NA objectives. Here,
      we introduce a non-descanned MMM based on MAPMT that substantially overcomes most
      of these drawbacks. We show that we improve signal efficiency up to fourfold with
      limited image SNR degradation due to scattered emission photons. The excitation
      foci can also be spaced wider to cover the full FOV of the objective with minimal
      aberrations. The performance of this system is demonstrated by imaging
      interneuron morphological structures deep in the brains of living mice.

PMID- 25874162
TI  - Functional network mediates age-related differences in reaction time: a
      replication and extension study.
AB  - INTRODUCTION: A functional activation (i.e., ordinal trend) pattern was
      previously identified in both young and older adults during task-switching
      performance, the expression of which correlated with reaction time. The current
      study aimed to (1) replicate this functional activation pattern in a new group of
      fMRI activation data, and (2) extend the previous study by specifically examining
      whether the effect of aging on reaction time can be explained by differences in
      the activation of the functional activation pattern. METHOD: A total of 47 young
      and 50 older participants were included in the extension analysis. Participants
      performed task-switching as the activation task and were cued by the color of the
      stimulus for the task to be performed in each block. To test for replication, two
      approaches were implemented. The first approach tested the replicability of the
      predictive power of the previously identified functional activation pattern by
      forward applying the pattern to the Study II data and the second approach was
      rederivation of the activation pattern in the Study II data. RESULTS: Both
      approaches showed successful replication in the new data set. Using mediation
      analysis, expression of the pattern from the first approach was found to
      partially mediate age-related effects on reaction time such that older age was
      associated with greater activation of the brain pattern and longer reaction time,
      suggesting that brain activation efficiency (defined as "the rate of activation
      increase with increasing task difficulty" in Neuropsychologia 47, 2009, 2015) of
      the regions in the Ordinal trend pattern directly accounts for age-related
      differences in task performance. DISCUSSION: The successful replication of the
      functional activation pattern demonstrates the versatility of the Ordinal Trend
      Canonical Variates Analysis, and the ability to summarize each participant's
      brain activation map into one number provides a useful metric in multimodal
      analysis as well as cross-study comparisons.

PMID- 25874163
TI  - Modulation of the ?20-Hz motor-cortex rhythm to passive movement and tactile
      stimulation.
AB  - BACKGROUND: Integration of afferent somatosensory input with motor-cortex output
      is essential for accurate movements. Prior studies have shown that tactile input
      modulates motor-cortex excitability, which is reflected in the reactivity of the
      ? 20-Hz motor-cortex rhythm. ? 20-Hz rebound is connected to inhibition or
      deactivation of motor cortex whereas suppression has been associated with
      increased motor cortex activity. Although tactile sense carries important
      information for controlling voluntary actions, proprioception likely provides the
      most essential feedback for motor control. METHODS: To clarify how passive
      movement modulates motor-cortex excitability, we studied with
      magnetoencephalography (MEG) the amplitudes and peak latencies of suppression and
      rebound of the ? 20-Hz rhythm elicited by tactile stimulation and passive
      movement of right and left index fingers in 22 healthy volunteers. RESULTS:
      Passive movement elicited a stronger and more robust ? 20-Hz rebound than tactile
      stimulation. In contrast, the suppression amplitudes did not differ between the
      two stimulus types. CONCLUSION: Our findings suggest that suppression and rebound
      represent activity of two functionally distinct neuronal populations. The ? 20-Hz
      rebound to passive movement could be a suitable tool to study the functional
      state of the motor cortex both in healthy subjects and in patients with motor
      disorders.

PMID- 25874164
TI  - The neural correlates of subjectively perceived and passively matched loudness
      perception in auditory phantom perception.
AB  - INTRODUCTION: A fundamental question in phantom perception is determining whether
      the brain creates a network that represents the sound intensity of the auditory
      phantom as measured by tinnitus matching (in dB), or whether the phantom
      perception is actually only a representation of the subjectively perceived
      loudness. METHODS: In tinnitus patients, tinnitus loudness was tested in two
      ways, by a numeric rating scale for subjectively perceived loudness and a more
      objective tinnitus-matching test, albeit it is still a subjective measure.
      RESULTS: Passively matched tinnitus does not correlate with subjective numeric
      rating scale, and has no electrophysiological correlates. Subjective loudness, in
      a whole-brain analysis, is correlated with activity in the left anterior insula
      (alpha), the rostral/dorsal anterior cingulate cortex (beta), and the left
      parahippocampus (gamma). A ROI analysis finds correlations with the auditory
      cortex (high beta and gamma) as well. The theta band links gamma band activity in
      the auditory cortex and parahippocampus via theta-gamma nesting. CONCLUSIONS:
      Apparently the brain generates a network that represents subjectively perceived
      tinnitus loudness only, which is context dependent. The subjective loudness
      network consists of the anterior cingulate/insula, the parahippocampus, and the
      auditory cortex. The gamma band activity in the parahippocampus and the auditory
      cortex is functionally linked via theta-gamma nested lagged phase
      synchronization.

PMID- 25874165
TI  - The impact of transcranial direct current stimulation on inhibitory control in
      young adults.
AB  - BACKGROUND: There is increasing evidence that the dorso-lateral prefrontal cortex
      (DLPFC), a brain region related to reward and motivational processes, is involved
      in effective response inhibition and that decreased activity in this region
      coincides with reduced inhibitory capacity. Using transcranial direct current
      stimulation (tDCS) to manipulate cortical activation, this study examined whether
      cross-hemispheric tDCS over the DLPFC affected performance on an inhibitory
      control task. METHODS: Neurologically intact participants performed a modified
      Stroop color-word matching task before and after completing one of two tDCS
      conditions; (1) anodal stimulation over the left DLPFC or (2) sham tDCS. RESULTS:
      There was a statistically significant effect of tDCS condition on Stroop reaction
      time (RT) pre-post tDCS change scores. Participants who received anodal
      stimulation over the left DLPFC demonstrated statistically significant faster RT
      change scores on the Stroop items compared to participants in the sham condition.
      Although errors on Stroop incongruent items decreased before and after receiving
      the tDCS treatment, there were no significant differences in errors on Stroop
      items between the anodal stimulation over left DLPFC and sham tDCS conditions.
      Anodal tDCS, which is known to elevate neural excitation, may have enhanced
      activation levels in the left DLPFC and minimized impairment of inhibitory
      control, resulting in better task performance. CONCLUSIONS: Current findings
      provide preliminary evidence that increased excitation of the left DLPFC improves
      inhibitory control and are a step toward understanding the potential of tDCS for
      moderating deficits in inhibitory control.

PMID- 25874166
TI  - Functional connectivity of the striatum in experts of stenography.
AB  - INTRODUCTION: Stenography, or shorthand, is a unique set of skills that involves
      intensive training which is nearly life-long and orchestrating various brain
      functional modules, including auditory, linguistic, cognitive, mnemonic, and
      motor. Stenography provides cognitive neuroscientists with a unique opportunity
      to investigate the neural mechanisms underlying the neural plasticity that
      enables such a high degree of expertise. However, shorthand is quickly being
      replaced with voice recognition technology. We took this nearly final opportunity
      to scan the brains of the last alive shorthand experts of the Japanese language.
      METHODS: Thirteen right-handed stenographers and fourteen right-handed controls
      participated in the functional magnetic resonance imaging (fMRI) study. RESULTS:
      The fMRI data revealed plastic reorganization of the neural circuits around the
      putamen. The acquisition of expert skills was accompanied by structural and
      functional changes in the area. The posterior putamen is known as the execution
      center of acquired sensorimotor skills. Compared to nonexperts, the posterior
      putamen in stenographers had high covariation with the cerebellum and
      midbrain.The stenographers' brain developed different neural circuits from those
      of the nonexpert brain. CONCLUSIONS: The current data illustrate the vigorous
      plasticity in the putamen and in its connectivity to other relevant areas in the
      expert brain. This is a case of vigorous neural plastic reorganization in
      response to massive overtraining, which is rare especially considering that it
      occurred in adulthood.

PMID- 25874168
TI  - Current status of assisted reproductive technology in Korea, 2010.
AB  - OBJECTIVE: Great advances have been made in the field of assisted reproductive
      technology (ART) since the first in vitro fertilization (IVF) baby was born in
      Korea. This study was designed to report on the current status of ART therapy in
      South Korea between January 1 and December 31 of 2010. METHODS: A revised survey,
      originally developed by the International Committee Monitoring Assisted
      Reproductive Technologies, was sent to all available ART centers via email in
      2013. Fresh embryo transfer (FET) cases were categorized into standard IVF or
      intracytoplasmic sperm injections. These cases, the thawing embryo transfer (TET)
      cases, and other related procedures were surveyed. RESULTS: Data from 30,785 ART
      procedures were provided by 78 clinics. Of the 28,200 cycles in which oocytes
      were retrieved, 92.2% of these cycles were completely transferred. In addition,
      8,075 cycles were confirmed to be clinical pregnancies in the FET cycles, which
      represent a pregnancy rate of 28.6% per oocyte pick-up and 31.1% per embryo
      transfer. The most common number of embryos transferred in the FET was three
      embryos (37.3%) followed by two embryos (36.3%) and one embryo (14.0%). Of the
      6,648 TET cycles transferred, 2,356 clinical pregnancies were confirmed by
      ultrasonography. The most common number of embryos in the TET group was two
      embryos (43.4%) followed by three embryos (25.4%) and one embryo (18.9%).
      CONCLUSION: The clinical pregnancy rate per transfer in the FET cycles was
      similar in 2009 and 2010. Among the FET cycles where one or two embryos were
      transferred, the clinical pregnancy rate per transfer slightly increased from
      2009 (28.7%) to 2010 (32.9%).

PMID- 25874167
TI  - Endoplasmic reticulum stress in periimplantation embryos.
AB  - Stress coping mechanisms are critical to minimize or overcome damage caused by
      ever changing environmental conditions. They are designed to promote cell
      survival. The unfolded protein response (UPR) pathway is mobilized in response to
      the accumulation of unfolded proteins, ultimately in order to regain endoplasmic
      reticulum (ER) homeostasis. Various elements of coping responses to ER stress
      including Perk, Ask1, Bip, Chop, Gadd34, Ire1, Atf4, Atf6, and Xbp1 have been
      identified and were found to be inducible in oocytes and preimplantation embryos,
      suggesting that, as a normal part of the cellular adaptive mechanism, these
      coping responses, including the UPR, play a pivotal role in the development of
      preimplantation embryos. As such, the UPR-associated molecules and pathways may
      become useful markers for the potential diagnosis of stress conditions for
      preimplantation embryos. After implantation, ER stress-induced coping responses
      become physiologically important for a normal decidual response, placentation,
      and early organogenesis. Attenuation of ER stress coping responses by
      tauroursodeoxycholate and salubrinal was effective for prevention of cell death
      of cultured embryos. Further elucidation of new and relevant ER stress coping
      responses in periimplantation embryos might contribute to a comprehensive
      understanding of the regulation of normal development of embryonic development
      and potentiation of embryonic development in vitro. 

PMID- 25874169
TI  - The parental origin correlates with the karyotype of human embryos developing
      from tripronuclear zygotes.
AB  - OBJECTIVE: It has previously been suggested that embryos developing from
      intracytoplasmic sperm-injected (ICSI) zygotes with three pronuclei (3PN) are
      endowed with a mechanism for self-correction of triploidy to diploidy. 3PN are
      also observed in zygotes after conventional in vitro fertilization (IVF). The
      parental origin, however, differs between the two fertilization methods. Whereas
      the vast majority of 3PN IVF zygotes are of dispermic origin and thus more likely
      to have two centrioles, the 3PN ICSI zygotes are digynic in origin and therefore,
      more likely to have one centriole. In the present study, we examine whether the
      parental origin of 3PN embryos correlates with the karyotype. METHODS: The
      karyotype of each nucleus was estimated using four sequential fluorescence in
      situ hybridizations-each with two probes-resulting in quantitative information of
      8 different chromosomes. The karyotypes were then compared and correlated to the
      parental origin. RESULTS: 3PN ICSI embryos displayed a significantly larger and
      more coordinated reduction from the assumed initial 3 sets of chromosomes than
      3PN IVF embryos. CONCLUSION: The differences in the parental origin-and hence the
      number of centrioles-between the 3PN IVF and the 3PN ICSI zygotes are likely to
      be the cause of the differences in karyotypes.

PMID- 25874171
TI  - Acknowledgment to reviewers for 2014.

PMID- 25874170
TI  - Comparison of the effect of different media on the clinical outcomes of the
      density-gradient centrifugation/swim-up and swim-up methods.
AB  - OBJECTIVE: Sperm must be properly prepared in in vitro fertilization (IVF)-embryo
      transfer (ET) programs in order to control the fertilization rate and ensure that
      embryos are of high quality and have appropriate developmental abilities. The
      objective of this study was to determine the most optimal sperm preparation
      method for IVF. METHODS: Patients less than 40 years of age who participated in a
      fresh IVF-ET cycle from November 2012 to March 2013 were included in this study.
      Poor responders with less than three mature oocytes were excluded. Ham's F-10
      medium or sperm-washing medium (SWM) was used in combination with the density
      gradient centrifugation/swim-up (DGC-SUP) or SUP methods for sperm preparation. A
      total of 429 fresh IVF-ET cycles were grouped according to the media and methods
      used for sperm preparation and retrospectively analyzed (DGC-SUP/Ham's F-10,
      n=82; DGC-SUP/SWM, n=43; SUP/Ham's F-10, n=181; SUP/SWM, n=123). RESULTS: There
      were no significant differences among these four groups with respect to the mean
      age of the female partners, duration of infertility, number of previous IVF
      cycles, and retrieved oocytes. We determined that both the DGC-SUP and SUP
      methods for sperm preparation from whole semen, using either Ham's F-10 or SWM
      media, result in comparable clinical outcomes, including fertilization and
      pregnancy rates. CONCLUSION: We suggest that both media and both methods for
      sperm preparation can be used for selecting high-quality sperm for assistive
      reproductive technology programs.

PMID- 25874172
TI  - Contemporary treatment with radiosurgery for spine metastasis and spinal cord
      compression in 2015.
AB  - With the progress of image-guided localization, body immobilization system, and
      computerized delivery of intensity-modulated radiation delivery, it became
      possible to perform spine radiosurgery. The next question is how to translate the
      high technology treatment to the clinical application. Clinical trials have been
      performed to demonstrate the feasibility of spine radiosurgery and efficacy of
      the treatment in the setting of spine metastasis, leading to the randomized
      trials by a cooperative group. Radiosurgery has also demonstrated its efficacy to
      decompress the spinal cord compression in selected group of patients. The
      experience indicates that spine radiosurgery has a potential to change the
      clinical practice in the management of spine metastasis and spinal cord
      compression. 

PMID- 25874173
TI  - Treatment outcomes of neoadjuvant concurrent chemoradiotherapy followed by
      esophagectomy for patients with esophageal cancer.
AB  - PURPOSE: To evaluate treatment outcomes and determine prognostic factors in
      patients with esophageal cancer treated with esophagectomy after neoadjuvant
      chemoradiotherapy (NCRT). MATERIALS AND METHODS: We retrospectively evaluated 39
      patients with esophageal cancer who underwent concurrent chemoradiotherapy
      followed by esophagectomy between 2002 and 2012. Initial clinical stages of
      patients were stage IB in 1 patient (2.6%), stage II in 5 patients (12.9%), and
      stage III in 33 patients (84.6%). RESULTS: The median age of all the patients was
      62 years, and the median follow-up period was 17 months. The 3-year overall
      survival (OS) rate was 33.6% in all the patients. The 3-year locoregional
      recurrence-free survival (LRFS) rate was 33.7%. In multivariate analysis with
      covariates of age, the Eastern Cooperative Oncology Group performance status,
      hypertension, diabetes mellitus, tumor length, clinical response, clinical stage,
      pathological response, pathological stage, lymphovascular invasion, surgical
      type, and radiotherapy to surgery interval, only pathological stage was an
      independent significant prognostic factor affecting both OS and LRFS. The
      complications in postoperative day 90 were pneumonia in 9 patients, anastomotic
      site leakage in 3 patients, and anastomotic site stricture in 2 patients.
      Postoperative 30-day mortality rate was 10.3% (4/39); the cause of death among
      these 4 patients was respiratory failure in 3 patients and myocardial infarction
      in one patient. CONCLUSION: Only pathological stage was an independent prognostic
      factor for both OS and LRFS in patients with esophageal cancer treated with
      esophagectomy after NCRT. We could confirm the significant role of NCRT in
      downstaging the initial tumor bulk and thus resulting in better survival of
      patients who gained earlier pathological stage after NCRT.

PMID- 25874174
TI  - Clinical and biochemical outcomes of men undergoing radical prostatectomy or
      radiation therapy for localized prostate cancer.
AB  - PURPOSE: We analyzed outcomes of patients with prostate cancer undergoing either
      radical retropubic prostatectomy (RRP) +/- salvage radiation or definitive
      radiation therapy (RT) +/- androgen deprivation. MATERIALS AND METHODS: From 2003
      2010 there were 251 patients who underwent RRP and 469 patients who received RT
      (>=7,560 cGy) for prostate cancer. Kaplan-Meier analysis was performed with the
      log-rank test to compare biochemical control (bCR), distant metastatic-free
      survival (DMPFS), and prostate cancer-specific survival (PCSS) between the two
      groups. RESULTS: The median follow-up was 70 months and 61.3% of the men were
      African American. For low risk disease the 6-year bCR were 90.3% for RT and 85.6%
      for RRP (p = 0.23) and the 6-year post-salvage bCR were 90.3% vs. 90.9%,
      respectively (p = 0.84). For intermediate risk disease the 6-year bCR were 82.6%
      for RT and 59.7% for RRP (p < 0.001) and 82.6% vs. 74.0%, respectively, after
      including those salvaged with RT (p = 0.06). For high risk disease, the 6-year
      bCR were 67.4% for RT and 41.3% for RRP (p < 0.001) and after including those
      salvaged with RT was 67.4% vs. 43.1%, respectively (p < 0.001). However, there
      were no significant differences between the two groups in regards to DMPFS or
      PCSS. CONCLUSION: Treatment approaches utilizing RRP +/- salvage radiation or RT
      +/- androgen deprivation yielded equivalent DMPFS and PCSS outcomes. Biochemical
      control rates, using their respective definitions, appeared equivalent or better
      in those who received treatment with RT.

PMID- 25874176
TI  - Post-treatment intracranial hemorrhage of brain metastases from hepatocellular
      carcinoma.
AB  - PURPOSE: To evaluate the incidence and risk factors of post-treatment
      intracranial hemorrhage of brain metastases from hepatocellular carcinoma (HCC).
      MATERIALS AND METHODS: Medical records of 81 patients who have been diagnosed of
      brain metastases from HCC and underwent surgery, radiosurgery and/or whole brain
      radiotherapy (WBRT) between January 2000 and December 2013 were retrospectively
      reviewed. RESULTS: Intracranial hemorrhage was present in 64 patients (79%) at
      the time of diagnosis. Median value of alpha-fetoprotein (AFP) level was 1,700
      ng/mL. The Eastern Cooperative Oncology Group (ECOG) performance status for 20
      patients was greater than 2. Fifty-seven patients underwent WBRT and the others
      were treated with surgery and/or radiosurgery without WBRT. During follow-up, 12
      events of intracranial hemorrhage after treatment were identified. Three-month
      post-treatment hemorrhage rate was 16.1%. Multivariate analyses revealed that
      ECOG performance status, AFP, and WBRT were associated with post-treatment
      hemorrhage (p = 0.013, 0.013, and 0.003, respectively). Kaplan-Meier analysis
      showed that 3-month post-treatment hemorrhage rate of new lesion was higher in
      patients treated without WBRT, although statistical significance was not reached.
      (18.6% vs. 4.6%; p = 0.104). Ten of 12 patients with post-treatment hemorrhage
      died with neurologic cause. CONCLUSION: WBRT should be considered to prevent post
      treatment hemorrhage in the treatment of brain metastases from HCC.

PMID- 25874175
TI  - Outcome analysis in patients with uterine sarcoma.
AB  - PURPOSE: To analyze the prognostic factors for survivals and to evaluate the
      impact of postoperative whole pelvic radiotherapy (WPRT) on pelvic failure in
      patients with uterine sarcoma treated with radical surgery. MATERIALS AND
      METHODS: We retrospectively analyzed 75 patients with uterine sarcoma who
      underwent radical surgery with (n = 22) or without (n = 53) radiotherapy between
      1990 and 2010. There were 23 and 52 patients with carcinosarcoma and non
      carcinosarcoma (leiomyosarcoma, 22; endometrial stromal sarcoma, 25; others, 5),
      respectively. The median follow-up period was 64 months (range, 17 to 269
      months). RESULTS: The 5-year overall survival (OS) and pelvic failure-free
      survival (PFFS) of total patients was 64.2% and 83.4%, respectively. Multivariate
      analysis revealed that mitotic count (p = 0.006) was a significant predictor of
      OS. However, factors were not found to be associated with PFFS. On analyzing each
      of the histologic subtypes separately, postoperative WPRT significantly reduced
      pelvic failure in patients with carcinosarcoma (10.0% vs. 53.7%; p = 0.046), but
      not in patients with non-carcinosarcoma (12.5% vs. 9.9%; p = 0.866). Among the
      patients with carcinosarcoma, 4 patients (17%) had recurrence within the pelvis
      and 3 patients (13%) had recurrence in other sites as an initial failure, whereas
      among the patients with non-carcinosarcoma, 3 patients (6%) experienced pelvic
      failure and 13 patients (25%) experienced distant failure. CONCLUSION: The most
      significant predictor of OS was mitotic count. Based on the improved PFFS after
      postoperative WPRT only in patients with carcinosarcoma and the difference in
      patterns of failure between histologic subtypes, optimal adjuvant treatment
      options should be offered to patients based on the risk of recurrence patterns.

PMID- 25874177
TI  - New methods for optical distance indicator and gantry angle quality control tests
      in medical linear accelerators: image processing by using a 3D phantom.
AB  - PURPOSE: In order to keep the acceptable level of the radiation oncology linear
      accelerators, it is necessary to apply a reliable quality assurance (QA) program.
      MATERIALS AND METHODS: The QA protocols, published by authoritative
      organizations, such as the American Association of Physicists in Medicine (AAPM),
      determine the quality control (QC) tests which should be performed on the medical
      linear accelerators and the threshold levels for each test. The purpose of this
      study is to increase the accuracy and precision of the selected QC tests in order
      to increase the quality of treatment and also increase the speed of the tests to
      convince the crowded centers to start a reliable QA program. A new method has
      been developed for two of the QC tests; optical distance indicator (ODI) QC test
      as a daily test and gantry angle QC test as a monthly test. This method uses an
      image processing approach utilizing the snapshots taken by the CCD camera to
      measure the source to surface distance (SSD) and gantry angle. RESULTS: The new
      method of ODI QC test has an accuracy of 99.95% with a standard deviation of
      0.061 cm and the new method for gantry angle QC has a precision of 0.43 degrees .
      The automated proposed method which is used for both ODI and gantry angle QC
      tests, contains highly accurate and precise results which are objective and the
      human-caused errors have no effect on the results. CONCLUSION: The results show
      that they are in the acceptable range for both of the QC tests, according to AAPM
      task group 142.

PMID- 25874178
TI  - Virtual lymph node analysis to evaluate axillary lymph node coverage provided by
      tangential breast irradiation.
AB  - PURPOSE: To investigate the coverage of axillary lymph node with tangential
      breast irradiation fields by using virtual lymph node (LN) analysis. MATERIALS
      AND METHODS: Forty-eight women who were treated with whole breast irradiation
      after breast-conserving surgery were analyzed. The axillary and breast volumes
      were delineated according to the Radiation Therapy Oncology Group (RTOG)
      contouring atlas. To generate virtual LN contours, preoperative
      fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT)
      scans with identifiable LN were fused with the CT scans, and the virtual LN
      contour were delineated on the CT. RESULTS: The median level I and II axillary
      volume coverage percentages at the VD95% line were 33.5% (range, 5.3% to 90.4%)
      and 0.6% (range, 0.0% to 14.6%), respectively. Thirty-one LNs in 18 patients were
      delineated (26 in level I and 5 in level II). In the level I axilla, 84.6% of
      virtual LNs were encompassed by the 95% isodose line. In the level II axilla, by
      contrast, none of the virtual LNs were encompassed by the 95% isodose volumes.
      There was a substantial discrepancy between the RTOG contouring atlas-based
      axillary volume analysis and the virtual LN analysis, especially for the level I
      axillary coverage. The axillary volume coverage was associated with the body mass
      index (BMI) and breast volume. CONCLUSION: The tangential breast irradiation did
      not deliver adequate therapeutic doses to the axillary region, particularly those
      in the level II axilla. Patients with small breast volumes or lower BMI showed
      reduced axillary coverage from the tangential breast fields. For axillary LN
      irradiation, individualized anatomy-based radiation fields for patients would be
      necessary.

PMID- 25874179
TI  - CT Fluoroscopy-guided Aspiration of Intracerebral Hematomas: Technique and
      Outcomes.
AB  - OBJECTIVE: The authors evaluated the feasibility and targeting accuracy of CT
      fluoroscopy (CTF)-guided catheter placement and aspiration of intracerebral
      hematoma (ICH)s. MATERIALS AND METHODS: Nine patients (mean age, 63.3 +/- 15.3
      years) were treated by CTF-guided hematoma aspiration under local anesthesia. The
      targeting errors in the lesion center, volume of the aspirated hematoma, accuracy
      of the final catheter position, procedure time, and clinical outcomes were
      evaluated. RESULTS: All catheters were successfully placed in the center of the
      hematoma. The mean volume of the aspirated hematoma was 20.6 +/- 8.8 mL (pre
      treatment, 44.7 +/- 20.1 mL; post-treatment, 24.1 +/- 13.8 mL). The average
      procedure time was 25.1 minutes (range, 18-32 minutes). In one case with a scanty
      residual hematoma, the catheter was removed at the end of the procedure. In the
      remaining eight cases, the catheter was left in the residual hematoma for
      drainage and all catheter tips were accurately located in the final position.
      There were no procedure-related complications, including rebleeding and
      infection. CONCLUSION: CTF-guided ICH aspiration is a feasible, quick, and
      accurate procedure which could substitute for stereotactic methods. The accurate
      catheter position provided by real-time observation enables an effective
      aspiration and drainage of hematomas.

PMID- 25874180
TI  - A suction thrombectomy technique: a rapid and effective method for intra-arterial
      thrombolysis.
AB  - OBJECTIVE: During mechanical thrombolysis, to reduce procedure-related
      complications and time, the authors have performed a simple suction thrombectomy
      technique. In this article, the authors describe the technical details and
      clinical outcomes of this technique. MATERIALS AND METHODS: From January 2013 to
      December 2013, 14 consecutive acute ischemic stroke (AIS) patients with large
      cerebral arterial occlusions in the middle cerebral artery (MCA; n = 7), internal
      cerebral artery (ICA; n = 5), basilar artery (BA; n = 1), and a tandem lesion
      (ICA and MCA; n = 1) were treated using this technique. The proximal part of the
      occluding clot was aspirated or captured and retrieved as one piece using a large
      bored microcatheter by applying negative suction pressure using a 50 mL syringe.
      RESULTS: Overall recanalization rate was 85.7% (12 patients). In the 8 patients
      in whom this technique was used alone, the recanalization rate was 87.5% (7
      patients). The median procedural duration was 30 minutes (range 17-112) in these
      7 patients. Distal embolism did not occur. Two patients developed post-procedural
      intracerebral hemorrhages and one was symptomatic. His modified Rankin Scale
      (mRS) score at 90 days was 4. CONCLUSION: This technique is a feasible, fast, and
      safe method for treatment of AIS.

PMID- 25874181
TI  - Contrast extravasation on computed tomography angiography imitating a basilar
      artery trunk aneurysm in subsequent conventional angiogram-negative subarachnoid
      hemorrhage: report of two cases with different clinical courses.
AB  - Contrast extravasation on computed tomography angiography (CTA) is rare but
      becoming more common, with increasing use of CTA for various cerebral vascular
      diseases. We report on two cases of spontaneous subarachnoid hemorrhage (SAH) in
      which the CTA showed a saccular lesion of the upper basilar trunk suggesting a
      ruptured aneurysm. However, no vascular lesion was observed on immediate
      subsequent digital subtraction angiography (DSA). In one case, repeated follow up
      DSA was also negative. The patient was treated conservatively and discharged with
      no neurologic deficit. In the other case, the patient showed sudden mental
      deterioration on the third hospital day and her brain CT showed rebleeding. The
      immediate follow up DSA showed contrast stagnation in the vicinity of the upper
      basilar artery, suggestive of pseudoaneurysm. Double stent deployment at the
      disease segment was performed. Due to the frequent use of CTA, contrast
      extravasation is an increasingly common observation. Physicians should be aware
      that basilar artery extravasation can mimic the appearance of an aneurysm. 

PMID- 25874182
TI  - Endovascular Stenting under Cardiac and Cerebral Protection for Subclavian Steal
      after Coronary Artery Bypass Grafting Due to Right Subclavian Artery Origin
      Stenosis.
AB  - Coronary-subclavian steal (CSS) can occur after coronary artery bypass grafting
      (CABG) using the internal thoracic artery (ITA). Subclavian artery (SA) stenosis
      proximal to the ITA graft causes CSS. We describe a technique for cardiac and
      cerebral protection during endovascular stenting for CSS due to right SA origin
      stenosis after CABG. A 64-year-old man with a history of CABG using the right ITA
      presented with exertional right arm claudication. Angiogram showed a CSS and
      retrograde blood flow in the right vertebral artery (VA) due to severe stenosis
      of the right SA origin. Endovascular treatment of the right SA stenosis was
      planned. For cardiac and cerebral protection, distal balloon protection by
      inflating a 5.2-F occlusion balloon catheter in the SA proximal to the origin of
      the right VA and ITA through the right brachial artery approach and distal filter
      protection of the right internal carotid artery (ICA) through the left femoral
      artery (FA) approach were performed. Endovascular stenting for SA stenosis from
      the right FA approach was performed under cardiac and cerebral protection by
      filter-protection of the ICA and balloon-protection of the VA and ITA. Successful
      treatment of SA severe stenosis was achieved with no complications. 

PMID- 25874183
TI  - Two cases of cavernous malformation presenting with unusual and large
      intracerebral hemorrhages.
AB  - Cavernous malformations (CMs), characterized by the presence of a hemosiderin rim
      and intralesional hemorrhage, are relatively common intracranial vascular
      malformations. Extralesional hemorrhages arising from CMs are seen in a minority
      of cases, but most of them show typical CM findings on magnetic resonance
      imaging. Here, the authors report two cases of pathologically confirmed CM
      presenting with unusual and large intracerebral hemorrhages, which were not
      surrounded by the typical hemosiderin rim. CMs presenting with large
      intracerebral hemorrhage should be considered in the differential diagnosis of
      massive intracerebral hemorrhages. 

PMID- 25874184
TI  - Delayed Perilesional Ischemic Stroke after Gamma-knife Radiosurgery for
      Unruptured Deep Arteriovenous Malformation: Two Case Reports of Radiation-induced
      Small Artery Injury as Possible Cause.
AB  - Radiation-induced vasculopathy is a rare occurrence, however, it is one of the
      most serious complications that can occur after gamma-knife radiosurgery (GKRS).
      The authors present two cases of incidentally found deep cerebral arteriovenous
      malformation (AVM), which were treated by GKRS, where subsequently there occurred
      delayed-onset cerebral infarction (11 and 17 months after GKRS) at an area
      adjacent to the AVM. In both cases, perforators of the M1 segment of the middle
      cerebral artery were included in the radiation field and delayed injury to these
      is suggested to be the mechanism of the ischemic event. 

PMID- 25874185
TI  - Iatrogenic carotid-cavernous fistula after stent assisted coil embolization of
      posterior communicating artery aneurysm.
AB  - Stent assisted coiling (SAC) is a useful technique for the treatment of wide
      necked complex aneurysm. As the frequency of SAC increases, stent-related
      complications such as thromboembolism, aneurysm rupture, and vessel rupture have
      been reported. However, to the best of our knowledge, carotid-cavernous fistula
      (CCF) after SAC has never been reported. The authors experienced a case of direct
      CCF after a SAC procedure for treatment of a complex posterior communicating
      artery (PCoA) aneurysm regrowth, which was treated by clip ligation 12 years
      before. The patient was managed conservatively and angiograms performed three
      months after the procedure showed the complete obliteration of the left PcoA
      aneurysm and the spontaneous disappearance of CCF. Navigation of Solitaire stent
      lumen with microcatheter can cause unexpected arterial injury, especially when
      the proximal tip is placed in the curved portion. It seems to be desirable to
      place the proximal tip of Solitaire stent in the straight portion whenever
      possible to reduce the risk of inadvertent arterial injury which might be caused
      by future navigation of stent lumen. 

PMID- 25874186
TI  - Superficial temporal artery pseudoaneurysm treated with manual compression alone.
AB  - Traumatic pseudoaneurysm of the superficial temporal artery (STA) is an uncommon
      lesion and resection of the lesion is the treatment of choice. Three patients
      with traumatic pseudoaneurysm of the STA treated with only manual compression of
      the lesions were examined for this study. We report on an effective and safe
      minimally invasive technique for treatment of traumatic pseudoaneurysm of the
      STA. 

PMID- 25874187
TI  - Ventriculoperitoneal shunt in a patient with ruptured blister aneurysm treated
      with pipeline embolization device.
AB  - Cerebral spinal fluid (CSF) diversion is frequently required in patients with
      aneurysmal subarachnoid hemorrhage who develop subsequent hydrocephalus.
      Procedures such as external ventricular drain (EVD) and ventriculoperitoneal
      shunt (VPS) usually carry a very low rate of complications. However, as flow
      diverting stents such as Pipeline Embolization Device (PED) become more widely
      available, flow diverters are being used in treatment of some ruptured complex
      aneurysms. EVD and VPS placement in the setting of dual antiplatelet therapy
      (DAT) in these patients are associated with a significant risk of intracranial
      hemorrhage. We describe a management strategy and surgical technique that can
      minimize hemorrhagic complications associated with VPS in patients on DAT after
      treatment with flow diverting stents. 

PMID- 25874188
TI  - Stereotactic Body Radiation Therapy for Prostate Cancer: What is the Appropriate
      Patient-Reported Outcome for Clinical Trial Design?
AB  - PURPOSE: Stereotactic body radiation therapy (SBRT) is increasingly utilized as
      primary treatment for clinically localized prostate cancer. Consensus regarding
      the appropriate patient-reported outcome (PRO) endpoints for clinical trials
      evaluating radiation modalities for early stage prostate cancer is lacking. To
      aid in clinical trial design, this study presents PROs over a 36-month period
      following SBRT for clinically localized prostate cancer. METHODS: Between
      February 2008 and September 2010, 174 hormone-naive patients with clinically
      localized prostate cancer were treated with 35-36.25 Gy SBRT (CyberKnife,
      Accuray) delivered in 5 fractions. Patients completed the validated Expanded
      Prostate Cancer Index Composite (EPIC)-26 questionnaire at baseline and all
      follow-ups. The proportion of patients developing a clinically significant
      decline in each EPIC domain score was determined. The minimally important
      difference (MID) was defined as a change of one-half the standard deviation from
      the baseline. Per Radiation Therapy Oncology Group (RTOG) 0938, we also examined
      the patients who experienced a decline in EPIC urinary domain summary score of >2
      points (unacceptable toxicity defined as >=60% of all patients reporting this
      degree of decline) and EPIC bowel domain summary score of >5 points (unacceptable
      toxicity defined as >55% of all patients reporting this degree of decline) from
      baseline to 1 year. RESULTS: A total of 174 patients at a median age of 69 years
      received SBRT with a minimum follow-up of 36 months. The proportion of patients
      reporting a clinically significant decline (MID for urinary/bowel are 5.5/4.4) in
      EPIC urinary/bowel domain scores was 34%/30% at 6 months, 40%/32.2% at 12 months,
      and 32.8%/21.5% at 36 months. The patients reporting a decrease in the EPIC
      urinary domain summary score of >2 points was 43.2% (CI: 33.7%, 54.6%) at 6
      months, 51.6% (CI: 43.4%, 59.7%) at 12 months, and 41.8% (CI: 33.3%, 50.6%) at 36
      months. The patients reporting a decrease in the EPIC bowel domain summary score
      of >5 points was 29.6% (CI: 21.9%, 39.3%) at 6 months, 29% (CI: 22%, 36.8%) at 12
      months, and 22.4% (CI: 15.7%, 30.4%) at 36 months. CONCLUSION: Following prostate
      SBRT, clinically significant urinary symptoms are more common than bowel
      symptoms. Our prostate SBRT treatment protocol meets the RTOG 0938 criteria for
      moving forward to a Phase III trial comparing it to conventionally fractionated
      radiation therapy. Notably, between 12 and 36 months, the proportion of patients
      reporting a significant decrease in both EPIC urinary and bowel domain scores
      declined, suggesting a late improvement in these symptom domains. Further
      investigation is needed to elucidate (1) which EPIC domains bear the greatest
      influence on post-treatment quality of life and (2) at what time point PRO
      endpoint(s) should be assessed.

PMID- 25874189
TI  - Association of hyperglycemia in a general Japanese population with late-night
      dinner eating alone, but not breakfast skipping alone.
AB  - The unhealthy habit of late-night-dinner eating (LNDE) is often observed in
      adults. Since LNDE can lead to breakfast skipping (BS) the next morning, we
      examined the associations of LNDE and BS with hyperglycemia (HbA1c >= 5.7% and/or
      pharmacotherapy for diabetes), separately and in combination, in 61,364
      apparently healthy Japanese adults aged 30-70 years. Although LNDE alone was
      significantly associated with hyperglycemia, even after adjustment for body mass
      index, BS alone was not. Our results indicate that hyperglycemia in the general
      Japanese population is associated with LNDE alone, but not BS alone. 

PMID- 25874190
TI  - Insulin initiation: bringing objectivity to choice.
AB  - The choice of initial insulin is often dictated by subjective criteria: the
      "severity" of diabetes, the ability of the person with diabetes to self inject,
      at specific times of the day, and the physician's personal experience. No
      objective criteria have been evolved by any expert body so far to help guide
      clinicians make an appropriate, and accurate, choice of initiating insulin.
      Neither have large studies been able to shed light on the preferred type of
      insulin regime for a particular individual. This communication suggests various
      objective parameters which may be used to inform this decision. 

PMID- 25874191
TI  - Safety of intravenous insulin aspart compared to regular human insulin in
      patients undergoing ICU monitoring post cardiac surgery: an Indian experience.
AB  - BACKGROUND: Poor perioperative glycemic control increases risk of infection,
      cardiovascular accidents and mortality in patients undergoing surgery. Tight
      glycemic control by insulin therapy is known to yield better outcomes in such
      patients. Intravenous (IV) insulin therapy with or without adjunctive
      subcutaneous insulin therapy is the mainstay of managing hyperglycemia in
      perioperative period. This observational study assessed the safety of IV Insulin
      Aspart (IAsp) as compared to Regular Human Insulin (RHI) in patients undergone
      cardiac surgery at a tertiary care hospital. METHODS: 203 patients received IV
      IAsp (n = 103) and RHI (n = 100) respectively. Safety was assessed by frequency
      and severity of adverse events (AEs) & serious adverse events (SAEs) during
      hospitalization. RESULTS: IAsp effectively controlled mean blood glucose levels
      to 159.87 +/- 41.41 mg/dl similar to RHI (160.77 +/- 44.39 mg/dl). No serious
      adverse event was reported. The incidence of hypoglycemia was similar in both the
      groups. The insulin infusion rate, time for which insulin infusion was withheld
      and mean blood glucose during hypoglycemia was significantly high in RHI group.
      CONCLUSION: This study has shown similar safety of IV IAsp as compared to IV RHI
      in the post cardiac surgery patients. However physicians preferred IAsp as it
      offers advantage during transition. IV IAsp offers an effective and safe option
      for managing hyperglycemia in patients in ICU post cardiac procedures.

PMID- 25874192
TI  - Blood pressure profile in school children (6-16 years) of southern India: a
      prospective observational study.
AB  - AIMS AND OBJECTIVE: To determine normal blood pressure (BP) in apparently
      healthy, asymptomatic school children in the age group of 6-16 years and to
      determine the correlation of BP values with different sex, weight, height, and
      body mass index (BMI) and also to find out prevalence of hypertension in school
      going population. MATERIALS AND METHODS: This prospective, observational study
      enrolled 3,302 urban children (1,658 boys and 1,644 girls) in the age group of 6
      16 years. These were analyzed to study the distribution pattern of systolic blood
      pressure (SBP) and diastolic blood pressure (DBP) at different ages, sex, weight,
      height, and BMI. The SBP and DBP were noted as per age and sex. The association
      was seen between mean SBP and mean DBP with weight, height, and BMI. Information
      was collected about the family history of hypertension and was correlated with
      the obtained SBP and DBP readings. RESULTS: The mean SBP in males at 6 years was
      99.69 +/- 3.62 mm of Hg, at 10 years was 102.20 +/- 2.16 mm of Hg, and at 16
      years was 115.33 +/- 1.26 mm of Hg. The mean SBP in females at 6 years was 96.55
      +/- 2.86 mm of Hg, at 10 years was 101.16 +/- 2.12 mm of Hg, and at 16 years was
      112.41 +/- 1.06 mm of Hg. The correlation coefficient for relationship between
      age and SBP in males and females was 0.89 and 0.91, respectively, and for DBP was
      0.92 and 0.90, respectively. The correlation coefficient for relationship between
      height and SBP in males and females was 0.91 and 0.93, respectively, and for DBP
      was 0.92 and 0.88, respectively. The correlation coefficient for relationship
      between weight and SBP in males and females was 0.92 and 0.92, respectively, and
      for DBP was 0.94 and 0.91, respectively. In the nomogram obtained in the study,
      95% of study population fall between mean +2SD and -2SD. CONCLUSION: The blood
      pressure (BP) (SBP and DBP) tends to increase with age, weight, height, and BMI.
      The BP values (SBP and DBP) increases grossly after 11 years of age. The students
      with positive family history of hypertension had higher valve when compared to
      other student. The BP of children and adolescents can be evaluated using the
      reference table according to age. The table provided helps to classify as
      "normal" or "hypertension" (>+2SD).

PMID- 25874193
TI  - Examining the Correlation between Objective Injury Parameters, Personality
      Traits, and Adjustment Measures among Burn Victims.
AB  - BACKGROUND: Burn victims experience immense physical and mental hardship during
      their process of rehabilitation and regaining functionality. We examined
      different objective burn-related factors as well as psychological ones, in the
      form of personality traits that may affect the rehabilitation process and its
      outcome. OBJECTIVE: To assess the influence and correlation of specific
      personality traits and objective injury-related parameters on the adjustment of
      burn victims post-injury. METHODS: Sixty-two male patients admitted to our burn
      unit due to burn injuries were compared with 36 healthy male individuals by use
      of questionnaires to assess each group's psychological adjustment parameters.
      Multivariate and hierarchical regression analysis was conducted to identify
      differences between the groups. RESULTS: A significant negative correlation was
      found between the objective burn injury severity (e.g., total body surface area
      and burn depth) and the adjustment of burn victims (p < 0.05, p < 0.001, Table
      3). Moreover, patients more severely injured tend to be more neurotic (p <
      0.001), and less extroverted and agreeable (p < 0.01, Table 4). CONCLUSION:
      Extroverted burn victims tend to adjust better to their post-injury life while
      the neurotic patients tend to have difficulties adjusting. This finding may
      suggest new tools for early identification of maladjustment-prone patients and
      therefore provide them with better psychological support in a more dedicated
      manner.

PMID- 25874194
TI  - Landscape and regional environmental analysis of the spatial distribution of
      hantavirus human cases in europe.
AB  - BACKGROUND: In Europe, the most prevalent hantavirus, Puumala virus, is
      transmitted by bank voles and causes nephropathia epidemica in human. The
      European spatial distribution of nephropathia epidemica is investigated here for
      the first time with a rich set of environmental variables. METHODS: The influence
      of variables at the landscape and regional level is studied through multilevel
      logistic regression, and further information on their effects across the
      different European ecoregions is obtained by comparing an overall niche model
      (boosted regression trees) with regressions by ecoregion. RESULTS: The presence
      of nephropathia epidemica is likely in populated regions with well-connected
      forests, more intense vegetation activity, low soil water content, mild summers,
      and cold winters. In these regions, landscapes with a higher proportion of built
      up areas in forest ecotones and lower minimum temperature in winter are expected
      to be more at risk. Climate and forest connectivity have a stronger effect at the
      regional level. If variables are staying at their current values, the models
      predict that nephropathia epidemica may know intensification but should not
      spread (although southern Sweden, the Norwegian coast, and the Netherlands should
      be kept under watch). CONCLUSION: Models indicate that large-scale modeling can
      lead to a very high predictive power. At large scale, the effect of one variable
      on disease may follow three response scenarios: the effect may be the same across
      the entire study area, the effect can change according to the variable value, and
      the effect can change depending on local specificities. Each of these scenarios
      impacts large-scale modeling differently.

PMID- 25874195
TI  - Improvement of resistant hypertension by nocturnal hemodialysis in a patient with
      end-stage kidney disease.
AB  - Resistant hypertension is a common and refractory complication of hemodialysis
      (HD) patients and is associated with a higher risk of cardiovascular morbidity
      and mortality. Here we present a case of resistant hypertension treated
      successfully by nocturnal HD. A 63-year-old female with end-stage kidney disease
      was hospitalized for severe headache, objective vertigo and persistent vomiting
      for 1 month on February 6, 2012. She had been on intermittent HD for 3 months,
      and her blood pressure maintained 200-240/100-130 mm Hg even after using 7 kinds
      of antihypertensive drugs including olmesartan, benazepril, nitrendipine,
      arotinolol, terazosin, clonidine and torasemide. A CT of the abdomen revealed a
      mild hyperplasia of the left adrenal gland (fig. 1). However, plasma renin,
      angiotensin and aldosterone were all within the normal range. Nocturnal extended
      HD was initiated with a blood flow rate of 150 ml/min and a dialysis time of 7 h.
      After 3 months of nocturnal HD, all symptoms were relieved and her systolic blood
      pressure started to decrease by 10-20 mm Hg. Six months later, the predialysis
      blood pressure was decreased to 140-160/90-100 mm Hg and the antihypertensive
      drugs were reduced to 4 kinds. Meanwhile, the blood biochemical parameters
      including hemoglobin, serum calcium, phosphate and parathyroid hormone were all
      controlled well during 2 years of treatment. This case indicates that nocturnal
      extended HD is probably a promising and effective choice for resistant
      hypertension in HD patients. 

PMID- 25874196
TI  - Surgical intervention after catheter removal in a case of refractory peritoneal
      dialysis-related peritonitis.
AB  - Peritonitis is the most common infection in peritoneal dialysis (PD) and has been
      noted to be not only a cause of mortality but also the leading cause of technique
      failure in patients maintained on PD. Appropriate management of peritonitis to
      improve patient outcome has been the focus of clinical practice. We report a case
      of refractory PD-related peritonitis with surgical intervention intending to
      control ongoing peritoneal infection despite aggressive antibiotics and timely
      catheter removal. Exploratory laparotomy was performed in this case, and an
      encapsulated abscess in the peritoneal and pelvic cavity was obliterated.
      Adhesiolysis was done simultaneously. Continuous postoperative peritoneal lavage
      and drainage were implemented. Symptoms dramatically improved after operation,
      and indwelling tubes were removed several days later. Finally, the patient
      recovered and switched to permanent hemodialysis without intra-abdominal
      complications. Our case suggested that appropriate and timely surgical
      intervention in refractory peritonitis is necessary for saving lives in certain
      subgroups of patients. Clearly, well-designed studies with large samples are
      warranted to explore this issue in more detail. 

PMID- 25874197
TI  - Formation of abnormal fistula on arteriovenous fistula in a patient with
      buttonhole cannulation: a case report.
AB  - Buttonhole cannulation has been suggested as a technique that may lead to a
      reduction in many complications when compared with other techniques such as rope
      ladder cannulation. Despite all above, some complications still continue, which
      may lead to a dysfunction of the arteriovenous fistula (AVF) and inadequate
      dialysis, having an impact on the quality of life of the patients or eventually
      making the vascular access unusable. We report a 47-year-old Chinese male with
      end-stage renal disease who had maintenance hemodialysis three times a week for 5
      years. The AVF on the left wrist was operated 5 years ago and proved to be
      functionally effective with some monitoring and surveillance measures in the
      fourth year of hemodialysis. Two months later, the buttonhole cannulation
      technique was applied due to fistula punctuation difficulty by previous
      aneurysmal dilatation. After 10 times of buttonhole cannulation, the edema on the
      left forearm of the patient indicated a dysfunction of the AVF. This was further
      confirmed by the HD02 hemodialysis monitor and a vascular ultrasound, revealing a
      recirculation of 87%, an abnormal fistula between the AVF and the vein together
      with thrombus, and aneurysmal dilatation near the anastomosis. The site of
      cannulation was changed to avoid heavy recirculation (reduced to 25%), and a new
      AVF on the left wrist was successfully operated. Abnormal fistula on the AVF and
      vein during buttonhole cannulation is rarely reported, which reminds us that
      vascular access surveillance should be done regularly before and during the
      process of construction to find a possible dysfunction of the AVF in patients
      undergoing buttonhole cannulation. 

PMID- 25874198
TI  - Sodium thiosulfate: an emerging treatment for calciphylaxis in dialysis patients.
AB  - Calciphylaxis is a rare but life-threatening complication seen in dialysis
      patients. We report a case with calciphylaxis and severe secondary
      hyperparathyroidism. Sodium thiosulfate (STS) was used for treatment in this
      case. The painful skin ulcers improved significantly soon after treatment, with a
      slight reduction in the calcium-phosphorus product. Total parathyroidectomy was
      carried out 6 months after the STS therapy, which successfully solved
      hyperparathyroidism and the high calcium-phosphorus profiles. Until now, no
      recurrence of calciphylaxis has been observed during the more than 7 years of
      follow-up. STS, as a chelating agent for calcium and iron, is an emerging
      treatment option for calciphylaxis; however, the mechanisms of STS in treating
      calciphylaxis are not clear. Our case demonstrates that STS treatment did not
      work through normalizing calcium-phosphorus profiles, although to optimize
      hyperparathyroidism and to control calcium and phosphorus levels is clearly part
      of the general treatment of calciphylaxis. The literature on STS treatment for
      calciphylaxis in dialysis patients was also reviewed. 

PMID- 25874199
TI  - The Relations between EGFR R521K Polymorphism and Risk of Cancer: Need for
      Clarification of Data in a Recent Meta-Analysis.

PMID- 25874200
TI  - Gene knockout identification using an extension of Bees Hill Flux Balance
      Analysis.
AB  - Microbial strain optimisation for the overproduction of a desired phenotype has
      been a popular topic in recent years. Gene knockout is a genetic engineering
      technique that can modify the metabolism of microbial cells to obtain desirable
      phenotypes. Optimisation algorithms have been developed to identify the effects
      of gene knockout. However, the complexities of metabolic networks have made the
      process of identifying the effects of genetic modification on desirable
      phenotypes challenging. Furthermore, a vast number of reactions in cellular
      metabolism often lead to a combinatorial problem in obtaining optimal gene
      knockout. The computational time increases exponentially as the size of the
      problem increases. This work reports an extension of Bees Hill Flux Balance
      Analysis (BHFBA) to identify optimal gene knockouts to maximise the production
      yield of desired phenotypes while sustaining the growth rate. This proposed
      method functions by integrating OptKnock into BHFBA for validating the results
      automatically. The results show that the extension of BHFBA is suitable,
      reliable, and applicable in predicting gene knockout. Through several experiments
      conducted on Escherichia coli, Bacillus subtilis, and Clostridium thermocellum as
      model organisms, extension of BHFBA has shown better performance in terms of
      computational time, stability, growth rate, and production yield of desired
      phenotypes. 

PMID- 25874202
TI  - A distributed multiagent system architecture for body area networks applied to
      healthcare monitoring.
AB  - In the last years the area of health monitoring has grown significantly,
      attracting the attention of both academia and commercial sectors. At the same
      time, the availability of new biomedical sensors and suitable network protocols
      has led to the appearance of a new generation of wireless sensor networks, the so
      called wireless body area networks. Nowadays, these networks are routinely used
      for continuous monitoring of vital parameters, movement, and the surrounding
      environment of people, but the large volume of data generated in different
      locations represents a major obstacle for the appropriate design, development,
      and deployment of more elaborated intelligent systems. In this context, we
      present an open and distributed architecture based on a multiagent system for
      recognizing human movements, identifying human postures, and detecting harmful
      activities. The proposed system evolved from a single node for fall detection to
      a multisensor hardware solution capable of identifying unhampered falls and
      analyzing the users' movement. The experiments carried out contemplate two
      different scenarios and demonstrate the accuracy of our proposal as a real
      distributed movement monitoring and accident detection system. Moreover, we also
      characterize its performance, enabling future analyses and comparisons with
      similar approaches. 

PMID- 25874203
TI  - aCGH-MAS: analysis of aCGH by means of multiagent system.
AB  - There are currently different techniques, such as CGH arrays, to study genetic
      variations in patients. CGH arrays analyze gains and losses in different regions
      in the chromosome. Regions with gains or losses in pathologies are important for
      selecting relevant genes or CNVs (copy-number variations) associated with the
      variations detected within chromosomes. Information corresponding to mutations,
      genes, proteins, variations, CNVs, and diseases can be found in different
      databases and it would be of interest to incorporate information of different
      sources to extract relevant information. This work proposes a multiagent system
      to manage the information of aCGH arrays, with the aim of providing an intuitive
      and extensible system to analyze and interpret the results. The agent roles
      integrate statistical techniques to select relevant variations and visualization
      techniques for the interpretation of the final results and to extract relevant
      information from different sources of information by applying a CBR system. 

PMID- 25874204
TI  - The advances in research on the pharmacological effects of Fructus Ligustri
      Lucidi.
AB  - Fructus Ligustri Lucidi is a well-known invigorator in Chinese materia medica
      with hepatoprotective effect, anticancer activity, antioxidant activity, and so
      on. And oleanolic acids are the major pharmacologically active components in
      Fructus Ligustri Lucidi. So it has great value in medical health, and may be
      developed to a complementary and alternative medicine through further research.
      In this paper, the advances in research on pharmacological effects of Fructus
      Ligustri Lucidi were summarized by reviewing the recent related literature. 

PMID- 25874201
TI  - MicroRNAs as potential biomarkers in cancer: opportunities and challenges.
AB  - MicroRNAs (miRNAs) are a group of small noncoding RNAs (ncRNAs) that
      posttranscriptionally regulate gene expression by targeting their corresponding
      messenger RNAs (mRNAs). Dysregulated miRNAs have been considered as a new type of
      ''oncomiRs" or ''tumor suppressors," playing essential roles in cancer initiation
      and progression. Using genome-wide detection methods, ubiquitously aberrant
      expression profiles of miRNAs have been identified in a broad array of human
      cancers, showing great potential as novel diagnostic and prognostic biomarkers of
      cancer with high specificity and sensitivity. The detectable miRNAs in tissue,
      blood, and other body fluids with high stability provide an abundant source for
      miRNA-based biomarkers in human cancers. Despite the fact that an increasing
      number of potential miRNA biomarkers have been reported, the transition of miRNAs
      based biomarkers from bench to bedside still necessitates addressing several
      challenges. In this review, we will summarize our current understanding of miRNAs
      as potential biomarkers in human cancers. 

PMID- 25874206
TI  - Analysis of environmental stress factors using an artificial growth system and
      plant fitness optimization.
AB  - The environment promotes evolution. Evolutionary processes represent
      environmental adaptations over long time scales; evolution of crop genomes is not
      inducible within the relatively short time span of a human generation. Extreme
      environmental conditions can accelerate evolution, but such conditions are often
      stress inducing and disruptive. Artificial growth systems can be used to induce
      and select genomic variation by changing external environmental conditions, thus,
      accelerating evolution. By using cloud computing and big-data analysis, we
      analyzed environmental stress factors for Pleurotus ostreatus by assessing,
      evaluating, and predicting information of the growth environment. Through the
      indexing of environmental stress, the growth environment can be precisely
      controlled and developed into a technology for improving crop quality and
      production. 

PMID- 25874205
TI  - Production and characterization of biodiesel using nonedible castor oil by
      immobilized lipase from Bacillus aerius.
AB  - A novel thermotolerant lipase from Bacillus aerius was immobilized on inexpensive
      silica gel matrix. The immobilized lipase was used for the synthesis of biodiesel
      using castor oil as a substrate in a solvent free system at 55 degrees C under
      shaking in a chemical reactor. Several crucial parameters affecting biodiesel
      yield such as incubation time, temperature, substrate molar ratio, and amount of
      lipase were optimized. Under the optimized conditions, the highest biodiesel
      yield was up to 78.13%. The characterization of synthesized biodiesel was done
      through FTIR spectroscopy, (1)H NMR spectra, and gas chromatography. 

PMID- 25874207
TI  - Measurement of liver iron concentration by MRI is reproducible.
AB  - PURPOSE: The objectives were (i) construction of a phantom to reproduce the
      behavior of iron overload in the liver by MRI and (ii) assessment of the
      variability of a previously validated method to quantify liver iron concentration
      between different MRI devices using the phantom and patients. MATERIALS AND
      METHODS: A phantom reproducing the liver/muscle ratios of two patients with
      intermediate and high iron overload. Nine patients with different levels of iron
      overload were studied in 4 multivendor devices and 8 of them were studied twice
      in the machine where the model was developed. The phantom was analysed in the
      same equipment and 14 times in the reference machine. RESULTS: FeCl3 solutions
      containing 0.3, 0.5, 0.6, and 1.2 mg Fe/mL were chosen to generate the phantom.
      The average of the intramachine variability for patients was 10% and for the
      intermachines 8%. For the phantom the intramachine coefficient of variation was
      always below 0.1 and the average of intermachine variability was 10% for moderate
      and 5% for high iron overload. CONCLUSION: The phantom reproduces the behavior of
      patients with moderate or high iron overload. The proposed method of calculating
      liver iron concentration is reproducible in several different 1.5 T systems.

PMID- 25874208
TI  - Biological effects of listeriolysin O: implications for vaccination.
AB  - Listeriolysin O (LLO) is a thiol-activated cholesterol-dependent pore-forming
      toxin and the major virulence factor of Listeria monocytogenes (LM). Extensive
      research in recent years has revealed that LLO exerts a wide array of biological
      activities, during the infection by LM or by itself as recombinant antigen. The
      spectrum of biological activities induced by LLO includes cytotoxicity, apoptosis
      induction, endoplasmic reticulum stress response, modulation of gene expression,
      intracellular calcium oscillations, and proinflammatory activity. In addition,
      LLO is a highly immunogenic toxin and the major target for innate and adaptive
      immune responses in different animal models and humans. Recently, the crystal
      structure of LLO has been published in detail. Here, we review the structure
      function relationship for this fascinating microbial molecule, highlighting the
      potential uses of LLO in the fields of biomedicine and biotechnology,
      particularly in vaccination. 

PMID- 25874210
TI  - Catalysis of rice straw hydrolysis by the combination of immobilized cellulase
      from Aspergillus niger on beta-cyclodextrin-Fe3O4 nanoparticles and ionic liquid.
AB  - Cellulase from Aspergillus niger was immobilized onto beta-cyclodextrin
      conjugated magnetic particles by silanization and reductive amidation. The
      immobilized cellulase gained supermagnetism due to the magnetic nanoparticles.
      Ninety percent of cellulase was immobilized, but the activity of immobilized
      cellulase decreased by 10%. In this study, ionic liquid (1-butyl-3
      methylimidazolium chloride) was introduced into the hydrolytic process because
      the original reaction was a solid-solid reaction. The activity of immobilized
      cellulase was improved from 54.87 to 59.11 U g immobilized cellulase(-1) at an
      ionic liquid concentration of 200 mM. Using immobilized cellulase and ionic
      liquid in the hydrolysis of rice straw, the initial reaction rate was increased
      from 1.629 to 2.739 g h(-1) L(-1). One of the advantages of immobilized cellulase
      is high reusability--it was usable for a total of 16 times in this study.
      Compared with free cellulase, magnetized cellulase can be recycled by magnetic
      field and the activity of immobilized cellulase was shown to remain at 85% of
      free cellulase without denaturation under a high concentration of glucose (15 g
      L(-1)). Therefore, immobilized cellulase can hydrolyze rice straw continuously
      compared with free cellulase. The amount of harvested glucose can be up to
      twentyfold higher than that from the hydrolysis by free cellulase.

PMID- 25874209
TI  - Utility of microRNAs and siRNAs in cervical carcinogenesis.
AB  - MicroRNAs and siRNAs belong to a family of small noncoding RNAs which bind
      through partial sequence complementarity to 3'-UTR regions of mRNA from target
      genes, resulting in the regulation of gene expression. MicroRNAs have become an
      attractive target for genetic and pharmacological modulation due to the critical
      function of their target proteins in several signaling pathways, and their
      expression profiles have been found to be altered in various cancers. A promising
      technology platform for selective silencing of cell and/or viral gene expression
      using siRNAs is currently in development. Cervical cancer is the most common
      cancer in women in the developing world and sexually transmitted infection with
      HPV is the cause of this malignancy. Therefore, a cascade of abnormal events is
      induced during cervical carcinogenesis, including the induction of genomic
      instability, reprogramming of cellular metabolic pathways, deregulation of cell
      proliferation, inhibition of apoptotic mechanisms, disruption of cell cycle
      control mechanisms, and alteration of gene expression. Thus, in the present
      review article, we highlight new research on microRNA expression profiles which
      may be utilized as biomarkers for cervical cancer. Furthermore, we discuss
      selective silencing of HPV E6 and E7 with siRNAs which represents a potential
      gene therapy strategy against cervical cancer. 

PMID- 25874211
TI  - Osteoprotective effect of cordycepin on estrogen deficiency-induced osteoporosis
      in vitro and in vivo.
AB  - The purpose of this study was to verify the effect of cordycepin on
      ovariectomized osteopenic rats. Fifty Wistar female rats used were divided into 5
      groups: (1) sham-operation rats (control), (2) ovariectomized (OVX) rats with
      osteopenia, and (3) OVX'd rats with osteopenia treated with cordycepin (5 mg, 10
      mg, and 20 mg) for 8 weeks. After the rats were treated orally with cordycepin,
      serum alkaline phosphatase (ALP), tartrate resistant acid phosphatase (TRAP),
      serum osteocalcin (OC), homocysteine (HCY) , C-terminal crosslinked telopeptides
      of collagen type I (CTX) level, and oxidative stress were examined, respectively.
      The femoral neck was used for mechanical compression testing. At the same time,
      we further investigated the effect of cordycepin in vitro assay. The beneficial
      effects of cordycepin on improvement of osteoporosis in rats were attributable
      mainly to decrease ALP activity, TRAP activity, and CTX level. At the same time,
      cordycepin also increases the OC level in ovariectomized osteopenic rats. The
      histological examination clearly showed that dietary cordycepin can prevent bone
      loss caused by estrogen deficiency. These experimental results suggest that
      complement cordycepin is protective after ovariectomized osteopenic in specific
      way. 

PMID- 25874212
TI  - Evolution of genetic techniques: past, present, and beyond.
AB  - Genetics is the study of heredity, which means the study of genes and factors
      related to all aspects of genes. The scientific history of genetics began with
      the works of Gregor Mendel in the mid-19th century. Prior to Mendel, genetics was
      primarily theoretical whilst, after Mendel, the science of genetics was broadened
      to include experimental genetics. Developments in all fields of genetics and
      genetic technology in the first half of the 20th century provided a basis for the
      later developments. In the second half of the 20th century, the molecular
      background of genetics has become more understandable. Rapid technological
      advancements, followed by the completion of Human Genome Project, have
      contributed a great deal to the knowledge of genetic factors and their impact on
      human life and diseases. Currently, more than 1800 disease genes have been
      identified, more than 2000 genetic tests have become available, and in
      conjunction with this at least 350 biotechnology-based products have been
      released onto the market. Novel technologies, particularly next generation
      sequencing, have dramatically accelerated the pace of biological research, while
      at the same time increasing expectations. In this paper, a brief summary of
      genetic history with short explanations of most popular genetic techniques is
      given. 

PMID- 25874213
TI  - Ultrafast cone-beam computed tomography: a comparative study of imaging protocols
      during image-guided therapy procedure.
AB  - OBJECTIVE: To evaluate two ultrafast cone-beam CT (UF-CBCT) imaging protocols
      with different acquisition and injection parameters regarding image quality and
      required contrast media during image-guided hepatic transarterial
      chemoembolization (TACE). METHODS: In 80 patients (male: 46, female: 34; mean
      age: 56.8 years; range: 33-83) UF-CBCT was performed during TACE for
      intraprocedural guidance. Imaging was performed using two ultrafast CBCT
      acquisition protocols with different acquisition and injection parameters
      (imaging protocol 1: acquisition time 2.54 s, and contrast 6 mL with 3 s delay;
      imaging protocol 2: acquisition time 2.72 s, and contrast 7 mL with 6 s delay).
      Image evaluation was performed with both qualitative and quantitative methods.
      Contrast injection volume and dose parameters were compared using values from the
      literature. RESULTS: Imaging protocol 2 provided significantly better (P < 0.05)
      image quality than protocol 1 at the cost of slightly higher contrast load and
      patient dose. Imaging protocol 1 provided good contrast perfusion but it mostly
      failed to delineate the tumors (P < 0.05). On the contrary, imaging protocol 2
      showed excellent enhancement of hepatic parenchyma, tumor, and feeding vessels.
      CONCLUSION: Tumor delineation, visualization of hepatic parenchyma, and feeding
      vessels are clearly possible using imaging protocol 2 with ultrafast CBCT
      imaging. A reduction of required contrast volume and patient dose were achieved
      due to the ultrafast CBCT imaging.

PMID- 25874214
TI  - Identification of subtype specific miRNA-mRNA functional regulatory modules in
      matched miRNA-mRNA expression data: multiple myeloma as a case.
AB  - Identification of miRNA-mRNA modules is an important step to elucidate their
      combinatorial effect on the pathogenesis and mechanisms underlying complex
      diseases. Current identification methods primarily are based upon miRNA-target
      information and matched miRNA and mRNA expression profiles. However, for
      heterogeneous diseases, the miRNA-mRNA regulatory mechanisms may differ between
      subtypes, leading to differences in clinical behavior. In order to explore the
      pathogenesis of each subtype, it is important to identify subtype specific miRNA
      mRNA modules. In this study, we integrated the Ping-Pong algorithm and
      multiobjective genetic algorithm to identify subtype specific miRNA-mRNA
      functional regulatory modules (MFRMs) through integrative analysis of three
      biological data sets: GO biological processes, miRNA target information, and
      matched miRNA and mRNA expression data. We applied our method on a heterogeneous
      disease, multiple myeloma (MM), to identify MM subtype specific MFRMs. The
      constructed miRNA-mRNA regulatory networks provide modular outlook at subtype
      specific miRNA-mRNA interactions. Furthermore, clustering analysis demonstrated
      that heterogeneous MFRMs were able to separate corresponding MM subtypes. These
      subtype specific MFRMs may aid in the further elucidation of the pathogenesis of
      each subtype and may serve to guide MM subtype diagnosis and treatment. 

PMID- 25874215
TI  - Sialic acid expression in the mosquito Aedes aegypti and its possible role in
      dengue virus-vector interactions.
AB  - Dengue fever (DF) is the most prevalent arthropod-borne viral disease which
      affects humans. DF is caused by the four dengue virus (DENV) serotypes, which are
      transmitted to the host by the mosquito Aedes aegypti that has key roles in DENV
      infection, replication, and viral transmission (vector competence). Mosquito
      saliva also plays an important role during DENV transmission. In this study, we
      detected the presence of sialic acid (Sia) in Aedes aegypti tissues, which may
      have an important role during DENV-vector competence. We also identified genome
      sequences encoding enzymes involved in Sia pathways. The cDNA for Aedes aegypti
      CMP-Sia synthase (CSAS) was amplified, cloned, and functionally evaluated via the
      complementation of LEC29.Lec32 CSAS-deficient CHO cells. AedesCSAS-transfected
      LEC29.Lec32 cells were able to express Sia moieties on the cell surface.
      Sequences related to alpha-2,6-sialyltransferase were detected in the Aedes
      aegypti genome. Likewise, we identified Sia-alpha-2,6-DENV interactions in
      different mosquito tissues. In addition, we evaluated the possible role of
      sialylated molecules in a salivary gland extract during DENV internalization in
      mammalian cells. The knowledge of early DENV-host interactions could facilitate a
      better understanding of viral tropism and pathogenesis to allow the development
      of new strategies for controlling DENV transmission. 

PMID- 25874216
TI  - Microalgae as sustainable renewable energy feedstock for biofuel production.
AB  - The world energy crisis and increased greenhouse gas emissions have driven the
      search for alternative and environmentally friendly renewable energy sources.
      According to life cycle analysis, microalgae biofuel is identified as one of the
      major renewable energy sources for sustainable development, with potential to
      replace the fossil-based fuels. Microalgae biofuel was devoid of the major
      drawbacks associated with oil crops and lignocelluloses-based biofuels. Algae
      based biofuels are technically and economically viable and cost competitive,
      require no additional lands, require minimal water use, and mitigate atmospheric
      CO2. However, commercial production of microalgae biodiesel is still not feasible
      due to the low biomass concentration and costly downstream processes. The
      viability of microalgae biodiesel production can be achieved by designing
      advanced photobioreactors, developing low cost technologies for biomass
      harvesting, drying, and oil extraction. Commercial production can also be
      accomplished by improving the genetic engineering strategies to control
      environmental stress conditions and by engineering metabolic pathways for high
      lipid production. In addition, new emerging technologies such as algal-bacterial
      interactions for enhancement of microalgae growth and lipid production are also
      explored. This review focuses mainly on the problems encountered in the
      commercial production of microalgae biofuels and the possible techniques to
      overcome these difficulties. 

PMID- 25874218
TI  - A comparative study of almond biodiesel-diesel blends for diesel engine in terms
      of performance and emissions.
AB  - This paper investigates the opportunity of using almond oil as a renewable and
      alternative fuel source. Different fuel blends containing 10, 30, and 50% almond
      biodiesel (B10, B30, and B50) with diesel fuel (B0) were prepared and the
      influence of these blends on emissions and some performance parameters under
      various load conditions were inspected using a diesel engine. Measured engine
      performance parameters have generally shown a slight increase in exhaust gas
      temperature and in brake specific fuel consumption and a slight decrease in brake
      thermal efficiency. Gases investigated were carbon monoxide (CO) and oxides of
      nitrogen (NOx). Furthermore, the concentration of the total particulate and the
      unburned fuel emissions in the exhaust gas were tested. A blend of almond
      biodiesel with diesel fuel gradually reduced the engine CO and total particulate
      emissions compared to diesel fuel alone. This reduction increased with more
      almond biodiesel blended into the fuel. Finally, a slight increase in engine NO x
      using blends of almond biodiesel was measured.

PMID- 25874217
TI  - Ureteral involvement and diabetes increase the risk of subsequent bladder
      recurrence after nephroureterectomy for upper urinary tract urothelial carcinoma.
AB  - OBJECTIVES: To investigate the prognostic factors for bladder recurrence after
      radical nephroureterectomy (RNU) in patients with upper urinary tract urothelial
      carcinoma (UUT-UC). METHODS: From 1994 to 2012, 695 patients with UUT-UC treated
      with RNU were enrolled in National Taiwan University Medical Center. Among them,
      532 patients with no prior bladder UC history were recruited for analysis. We
      assessed the impact of potentially prognostic factors on bladder recurrence after
      RNU. RESULTS: The median follow-up period was 47.8 months. In the Cox model,
      ureteral involvement and diabetes mellitus (DM) were significantly associated
      with a higher bladder recurrence rate in the multivariate analysis (hazard ratio
      [HR]: 1.838; P = 0.003 and HR: 1.821; P = 0.010, resp.). In the Kaplan-Meier
      analysis, DM patients with concomitant ureteral UC experienced about a threefold
      increased risk of bladder recurrence as compared to those without both factors
      (HR: 3.222; P < 0.001). Patients with either of the two risk factors experienced
      about a twofold increased risk as compared to those without both factors (with
      DM, HR: 2.184, P = 0.024; with ureteral involvement, HR: 2.006, P = 0.003).
      CONCLUSIONS: Ureteral involvement and DM are significantly related to bladder
      recurrence after RNU in patients with UUT-UC.

PMID- 25874219
TI  - Using the eServices platform for detecting behavior patterns deviation in the
      elderly assisted living: a case study.
AB  - World's aging population is rising and the elderly are increasingly isolated
      socially and geographically. As a consequence, in many situations, they need
      assistance that is not granted in time. In this paper, we present a solution that
      follows the CRISP-DM methodology to detect the elderly's behavior pattern
      deviations that may indicate possible risk situations. To obtain these patterns,
      many variables are aggregated to ensure the alert system reliability and minimize
      eventual false positive alert situations. These variables comprehend information
      provided by body area network (BAN), by environment sensors, and also by the
      elderly's interaction in a service provider platform, called eServices--Elderly
      Support Service Platform. eServices is a scalable platform aggregating a service
      ecosystem developed specially for elderly people. This pattern recognition will
      further activate the adequate response. With the system evolution, it will learn
      to predict potential danger situations for a specified user, acting preventively
      and ensuring the elderly's safety and well-being. As the eServices platform is
      still in development, synthetic data, based on real data sample and empiric
      knowledge, is being used to populate the initial dataset. The presented work is a
      proof of concept of knowledge extraction using the eServices platform
      information. Regardless of not using real data, this work proves to be an asset,
      achieving a good performance in preventing alert situations.

PMID- 25874220
TI  - A meta-analysis strategy for gene prioritization using gene expression, SNP
      genotype, and eQTL data.
AB  - In order to understand disease pathogenesis, improve medical diagnosis, or
      discover effective drug targets, it is important to identify significant genes
      deeply involved in human disease. For this purpose, many earlier approaches
      attempted to prioritize candidate genes using gene expression profiles or SNP
      genotype data, but they often suffer from producing many false-positive results.
      To address this issue, in this paper, we propose a meta-analysis strategy for
      gene prioritization that employs three different genetic resources--gene
      expression data, single nucleotide polymorphism (SNP) genotype data, and
      expression quantitative trait loci (eQTL) data--in an integrative manner. For
      integration, we utilized an improved technique for the order of preference by
      similarity to ideal solution (TOPSIS) to combine scores from distinct resources.
      This method was evaluated on two publicly available datasets regarding prostate
      cancer and lung cancer to identify disease-related genes. Consequently, our
      proposed strategy for gene prioritization showed its superiority to conventional
      methods in discovering significant disease-related genes with several types of
      genetic resources, while making good use of potential complementarities among
      available resources.

PMID- 25874221
TI  - Recent advances in molecular magnetic resonance imaging of liver fibrosis.
AB  - Liver fibrosis is a life-threatening disease with high morbidity and mortality
      owing to its diverse causes. Liver biopsy, as the current gold standard for
      diagnosing and staging liver fibrosis, has a number of limitations, including
      sample variability, relatively high cost, an invasive nature, and the potential
      of complications. Most importantly, in clinical practice, patients often reject
      additional liver biopsies after initiating treatment despite their being
      necessary for long-term follow-up. To resolve these problems, a number of
      different noninvasive imaging-based methods have been developed for accurate
      diagnosis of liver fibrosis. However, these techniques only reflect morphological
      or perfusion-related alterations in the liver, and thus they are generally only
      useful for the diagnosis of late-stage liver fibrosis (liver cirrhosis), which is
      already characterized by "irreversible" anatomic and hemodynamic changes. Thus,
      it is essential that new approaches are developed for accurately diagnosing early
      stage liver fibrosis as at this stage the disease may be "reversed" by active
      treatment. The development of molecular MR imaging technology has potential in
      this regard, as it facilitates noninvasive, target-specific imaging of liver
      fibrosis. We provide an overview of recent advances in molecular MR imaging for
      the diagnosis and staging of liver fibrosis and we compare novel technologies
      with conventional MR imaging techniques. 

PMID- 25874222
TI  - Reactive oxygen species, apoptosis, and mitochondrial dysfunction in hearing
      loss.
AB  - Reactive oxygen species (ROS) production is involved in several apoptotic and
      necrotic cell death pathways in auditory tissues. These pathways are the major
      causes of most types of sensorineural hearing loss, including age-related hearing
      loss, hereditary hearing loss, ototoxic drug-induced hearing loss, and noise
      induced hearing loss. ROS production can be triggered by dysfunctional
      mitochondrial oxidative phosphorylation and increases or decreases in ROS-related
      enzymes. Although apoptotic cell death pathways are mostly activated by ROS
      production, there are other pathways involved in hearing loss that do not depend
      on ROS production. Further studies of other pathways, such as endoplasmic
      reticulum stress and necrotic cell death, are required. 

PMID- 25874223
TI  - Preservation of cognitive performance with age during exertional heat stress
      under low and high air velocity.
AB  - Older adults may be at greater risk for occupational injuries given their reduced
      capacity to dissipate heat, leading to greater thermal strain and potentially
      cognitive decrements. PURPOSE: To examine the effects of age and increased air
      velocity, during exercise in humid heat, on information processing and attention.
      METHODS: Nine young (24 +/- 1 years) and 9 older (59 +/- 1 years) males cycled 4
      * 15 min (separated by 15 min rest) at a fixed rate of heat production (400 W) in
      humid heat (35 degrees C, 60% relative humidity) under 0.5 (low) and 3.0 (high)
      m.s(-1) air velocity wearing coveralls. At rest, immediately following exercise
      (end exercise), and after the final recovery, participants performed an
      abbreviated paced auditory serial addition task (PASAT, 2 sec pace). RESULTS:
      PASAT numbers of correct responses at end exercise were similar for young (low =
      49 +/- 3; high = 51 +/- 3) and older (low = 46 +/- 5; high = 47 +/- 4) males and
      across air velocity conditions, and when scored relative to age norms.
      Psychological sweating, or an increased sweat rate with the administration of the
      PASAT, was observed in both age groups in the high condition. CONCLUSION: No
      significant decrements in attention and speeded information processing were
      observed, with age or altered air velocity, following intermittent exercise in
      humid heat.

PMID- 25874224
TI  - Vector borne infections in Italy: results of the integrated surveillance system
      for West Nile disease in 2013.
AB  - The epidemiology of West Nile disease (WND) is influenced by multiple ecological
      factors and, therefore, integrated surveillance systems are needed for early
      detecting the infection and activating consequent control actions. As different
      animal species have different importance in the maintenance and in the spread of
      the infection, a multispecies surveillance approach is required. An integrated
      and comprehensive surveillance system is in place in Italy aiming at early
      detecting the virus introduction, monitoring the possible infection spread, and
      implementing preventive measures for human health. This paper describes the
      integrated surveillance system for WND in Italy, which incorporates data from
      veterinary and human side in order to evaluate the burden of infection in animals
      and humans and provide the public health authorities at regional and national
      levels with the information needed for a fine tune response. 

PMID- 25874225
TI  - Probabilistic inference of biological networks via data integration.
AB  - There is significant interest in inferring the structure of subcellular networks
      of interaction. Here we consider supervised interactive network inference in
      which a reference set of known network links and nonlinks is used to train a
      classifier for predicting new links. Many types of data are relevant to inferring
      functional links between genes, motivating the use of data integration. We use
      pairwise kernels to predict novel links, along with multiple kernel learning to
      integrate distinct sources of data into a decision function. We evaluate various
      pairwise kernels to establish which are most informative and compare individual
      kernel accuracies with accuracies for weighted combinations. By associating a
      probability measure with classifier predictions, we enable cautious
      classification, which can increase accuracy by restricting predictions to high
      confidence instances, and data cleaning that can mitigate the influence of
      mislabeled training instances. Although one pairwise kernel (the tensor product
      pairwise kernel) appears to work best, different kernels may contribute
      complimentary information about interactions: experiments in S. cerevisiae
      (yeast) reveal that a weighted combination of pairwise kernels applied to
      different types of data yields the highest predictive accuracy. Combined with
      cautious classification and data cleaning, we can achieve predictive accuracies
      of up to 99.6%. 

PMID- 25874227
TI  - RecRWR: a recursive random walk method for improved identification of diseases.
AB  - High-throughput methods such as next-generation sequencing or DNA microarrays
      lack precision, as they return hundreds of genes for a single disease profile.
      Several computational methods applied to physical interaction of protein networks
      have been successfully used in identification of the best disease candidates for
      each expression profile. An open problem for these methods is the ability to
      combine and take advantage of the wealth of biomedical data publicly available.
      We propose an enhanced method to improve selection of the best disease targets
      for a multilayer biomedical network that integrates PPI data annotated with
      stable knowledge from OMIM diseases and GO biological processes. We present a
      comprehensive validation that demonstrates the advantage of the proposed
      approach, Recursive Random Walk with Restarts (RecRWR). The obtained results
      outline the superiority of the proposed approach, RecRWR, in identifying disease
      candidates, especially with high levels of biological noise and benefiting from
      all data available. 

PMID- 25874226
TI  - Challenges in using circulating miRNAs as cancer biomarkers.
AB  - In the last years, circulating miRNAs have emerged as a new class of promising
      cancer biomarkers. Independent studies have shown the feasibility of using these
      small RNAs as tools for the diagnosis and prognosis of different types of
      malignancies as well as for predicting and possibly monitoring treatment
      response. However, despite an initial enthusiasm for their possible clinical
      application, widespread inconsistencies have been observed among the studies, and
      miRNA-based tools still represent the object of research within clinical
      diagnostic or treatment protocols. The poor overlap of results could be
      explained, at least in part, by preanalytical and analytical variables and donor
      related factors that could generate artefacts, impairing an accurate
      quantification of circulating miRNAs. In fact, critical issues are represented by
      nonuniform sample choice, handling, and processing, as well as by blood cell
      contamination in sample preparation and lack of consensus for data normalization.
      In this review, we address the potential technical biases and individual-related
      parameters that can influence circulating miRNA studies' outcome. The exciting
      potential of circulating miRNAs as cancer biomarkers could confer an important
      advance in the disease management, but their clinical significance might not be
      proven without a global consensus of procedures and standardized protocols for
      their accurate detection. 

PMID- 25874228
TI  - Agent-based spatiotemporal simulation of biomolecular systems within the open
      source MASON framework.
AB  - Agent-based modelling is being used to represent biological systems with
      increasing frequency and success. This paper presents the implementation of a new
      tool for biomolecular reaction modelling in the open source Multiagent Simulator
      of Neighborhoods framework. The rationale behind this new tool is the necessity
      to describe interactions at the molecular level to be able to grasp emergent and
      meaningful biological behaviour. We are particularly interested in characterising
      and quantifying the various effects that facilitate biocatalysis. Enzymes may
      display high specificity for their substrates and this information is crucial to
      the engineering and optimisation of bioprocesses. Simulation results demonstrate
      that molecule distributions, reaction rate parameters, and structural parameters
      can be adjusted separately in the simulation allowing a comprehensive study of
      individual effects in the context of realistic cell environments. While higher
      percentage of collisions with occurrence of reaction increases the affinity of
      the enzyme to the substrate, a faster reaction (i.e., turnover number) leads to a
      smaller number of time steps. Slower diffusion rates and molecular crowding
      (physical hurdles) decrease the collision rate of reactants, hence reducing the
      reaction rate, as expected. Also, the random distribution of molecules affects
      the results significantly. 

PMID- 25874229
TI  - Current status and future potential of energy derived from Chinese agricultural
      land: a review.
AB  - Energy crisis is receiving attention with regard to the global economy and
      environmental sustainable development. Developing new energy resources to
      optimize the energy supply structure has become an important measure to prevent
      energy shortage as well as achieving energy conservation and emission reduction
      in China. This study proposed the concept of energy agriculture and constructed
      an energy agricultural technical support system based on the analysis of energy
      supply and demand and China's foreign dependence on energy resources, combined
      with the function of agriculture in the energy field. Manufacturing technology
      equipment and agricultural and forestry energy, including crop or forestry plants
      and animal feces, were used in the system. The current status and future
      potential of China's marginal land resources, energy crop germplasm resources,
      and agricultural and forestry waste energy-oriented resources were analyzed.
      Developing the function of traditional agriculture in food production may promote
      China's social, economic, and environmental sustainable development and achieve
      energy saving and emission reduction. 

PMID- 25874230
TI  - Crocetin downregulates the proinflammatory cytokines in methylcholanthrene
      induced rodent tumor model and inhibits COX-2 expression in cervical cancer
      cells.
AB  - The effect of crocetin (C20H24O4) on methylcholanthrene- (MCA-) induced uterine
      cervical cancer in mice was studied in this paper. After the mice were treated
      orally with crocetin, maleic dialdehyde (MDA), polymorphonuclear cells (PMN),
      interleukin-1beta (IL-1beta), and tumor necrosis factor-alpha (TNF-alpha) were
      examined by ELISA or immunohistochemistry. The inducible nitric oxide synthase
      (iNOS) activation in HeLa cells was analyzed using fluorescence microscopy for
      light microscopic examination. The MCA mice showed a significant increase in
      plasma MDA, PMN, IL-1beta, TNF-alpha, and nitrates levels. At the same time, the
      mRNA level of COX-2 in HeLa cells was also significantly increased. These changes
      were attenuated by crocetin supplementation in the MCA mice. Crocetin
      supplementation in the MCA mice also showed protection against cervical cancer.
      These results suggest that crocetin may act as a chemopreventive and an anti
      inflammatory agent. 

PMID- 25874231
TI  - Human monocyte heat shock protein 72 responses to acute hypoxic exercise after 3
      days of exercise heat acclimation.
AB  - The aim of this study was to determine whether short-term heat acclimation (STHA)
      could confer increased cellular tolerance to acute hypoxic exercise in humans as
      determined via monocyte HSP72 (mHSP72) expression. Sixteen males were separated
      into two matched groups. The STHA group completed 3 days of exercise heat
      acclimation; 60 minutes cycling at 50% VO2peak in 40 degrees C 20% relative
      humidity (RH). The control group (CON) completed 3 days of exercise training in
      20 degrees C, 40% RH. Each group completed a hypoxic stress test (HST) one week
      before and 48 hours following the final day of CON or STHA. Percentage changes in
      HSP72 concentrations were similar between STHA and CON following HST1 (P = 0.97).
      STHA induced an increase in basal HSP72 (P = 0.03) with no change observed in CON
      (P = 0.218). Basal mHSP72 remained elevated before HST2 for the STHA group (P <
      0.05) and was unchanged from HST1 in CON (P > 0.05). Percent change in mHSP72 was
      lower after HST2 in STHA compared to CON (P = 0.02). The mHSP72 response to
      hypoxic exercise was attenuated following 3 days of heat acclimation. This is
      indicative of improved tolerance and ability to cope with the hypoxic insult,
      potentially mediated in part by increased basal reserves of HSP72.

PMID- 25874232
TI  - Delay of morphine tolerance by palmitoylethanolamide.
AB  - In spite of the potency and efficacy of morphine, its clinical application for
      chronic persistent pain is limited by the development of tolerance to the
      antinociceptive effect. The cellular and molecular mechanisms underlying morphine
      tolerance are complex and still unclear. Recently, the activation of glial cells
      and the release of glia-derived proinflammatory mediators have been suggested to
      play a role in the phenomenon. N-palmitoylethanolamine (PEA) is an endogenous
      compound with antinociceptive effects able to reduce the glial activation. On
      this basis, 30 mg kg(-1) PEA was subcutaneously daily administered in morphine
      treated rats (10 mg kg(-1) intraperitoneally, daily). PEA treatment significantly
      attenuated the development of tolerance doubling the number of days of morphine
      antinociceptive efficacy in comparison to the vehicle + morphine group. PEA
      prevented both microglia and astrocyte cell number increase induced by morphine
      in the dorsal horn; on the contrary, the morphine-dependent increase of spinal
      TNF-alpha levels was not modified by PEA. Nevertheless, the immunohistochemical
      analysis revealed significantly higher TNF-alpha immunoreactivity in astrocytes
      of PEA-protected rats suggesting a PEA-mediated decrease of cytokine release from
      astrocyte. PEA intervenes in the nervous alterations that lead to the lack of
      morphine antinociceptive effects; a possible application of this endogenous
      compound in opioid-based therapies is suggested.

PMID- 25874234
TI  - Identification of novel thyroid cancer-related genes and chemicals using shortest
      path algorithm.
AB  - Thyroid cancer is a typical endocrine malignancy. In the past three decades, the
      continued growth of its incidence has made it urgent to design effective
      treatments to treat this disease. To this end, it is necessary to uncover the
      mechanism underlying this disease. Identification of thyroid cancer-related genes
      and chemicals is helpful to understand the mechanism of thyroid cancer. In this
      study, we generalized some previous methods to discover both disease genes and
      chemicals. The method was based on shortest path algorithm and applied to
      discover novel thyroid cancer-related genes and chemicals. The analysis of the
      final obtained genes and chemicals suggests that some of them are crucial to the
      formation and development of thyroid cancer. It is indicated that the proposed
      method is effective for the discovery of novel disease genes and chemicals. 

PMID- 25874233
TI  - Biologic roles of estrogen receptor-beta and insulin-like growth factor-2 in
      triple-negative breast cancer.
AB  - Triple-negative breast cancer (TNBC) occurs in 10-15% of patients yet accounts
      for almost half of all breast cancer deaths. TNBCs lack expression of estrogen
      and progesterone receptors and HER-2 overexpression and cannot be treated with
      current targeted therapies. TNBCs often occur in African American and younger
      women. Although initially responsive to some chemotherapies, TNBCs tend to
      relapse and metastasize. Thus, it is critical to find new therapeutic targets. A
      second ER gene product, termed ERbeta, in the absence of ERalpha may be such a
      target. Using human TNBC specimens with known clinical outcomes to assess ERbeta
      expression, we find that ERbeta1 associates with significantly worse 5-year
      overall survival. Further, a panel of TNBC cell lines exhibit significant levels
      of ERbeta protein. To assess ERbeta effects on proliferation, ERbeta expression
      in TNBC cells was silenced using shRNA, resulting in a significant reduction in
      TNBC proliferation. ERbeta-specific antagonists similarly suppressed TNBC growth.
      Growth-stimulating effects of ERbeta may be due in part to downstream actions
      that promote VEGF, amphiregulin, and Wnt-10b secretion, other factors associated
      with tumor promotion. In vivo, insulin-like growth factor-2 (IGF-2), along with
      ERbeta1, is significantly expressed in TNBC and stimulates high ERbeta mRNA in
      TNBC cells. This work may help elucidate the interplay of metabolic and growth
      factors in TNBC. 

PMID- 25874235
TI  - Proteases and protease inhibitors of urinary extracellular vesicles in diabetic
      nephropathy.
AB  - Diabetic nephropathy (DN) is one of the major complications of diabetes mellitus
      (DM), leads to chronic kidney disease (CKD), and, ultimately, is the main cause
      for end-stage kidney disease (ESKD). Beyond urinary albumin, no reliable
      biomarkers are available for accurate early diagnostics. Urinary extracellular
      vesicles (UEVs) have recently emerged as an interesting source of diagnostic and
      prognostic disease biomarkers. Here we used a protease and respective protease
      inhibitor array to profile urines of type 1 diabetes patients at different stages
      of kidney involvement. Urine samples were divided into groups based on the level
      of albuminuria and UEVs isolated by hydrostatic dialysis and screened for
      relative changes of 34 different proteases and 32 protease inhibitors,
      respectively. Interestingly, myeloblastin and its natural inhibitor elafin showed
      an increase in the normo- and microalbuminuric groups. Similarly, a
      characteristic pattern was observed in the array of protease inhibitors, with a
      marked increase of cystatin B, natural inhibitor of cathepsins L, H, and B as
      well as of neutrophil gelatinase-associated Lipocalin (NGAL) in the
      normoalbuminuric group. This study shows for the first time the distinctive
      alterations in comprehensive protease profiles of UEVs in diabetic nephropathy
      and uncovers intriguing mechanistic, prognostic, and diagnostic features of
      kidney damage in diabetes. 

PMID- 25874236
TI  - Metformin treatment in type 2 diabetes in pregnancy: an active controlled,
      parallel-group, randomized, open label study in patients with type 2 diabetes in
      pregnancy.
AB  - AIMS: To assess the effect of metformin and to compare it with insulin treatment
      in patients with type 2 diabetes in pregnancy in terms of perinatal outcome,
      maternal complications, additional insulin requirement, and treatment
      acceptability. METHODS: In this randomized, open label study, 206 patients with
      type 2 diabetes in pregnancy who met the eligibility criteria were selected from
      the antenatal clinics. Insulin was added to metformin treatment when required, to
      maintain the target glycemic control. The patients were followed up till
      delivery. Maternal, and perinatal outcomes and pharmacotherapeutic
      characteristics were recorded on a proforma. RESULTS: Maternal characteristics
      were comparable in metformin and insulin treated group. 84.9% patients in
      metformin group required add-on insulin therapy at mean gestational age of 26.58
      +/- 3.85 weeks. Less maternal weight gain (P < 0.001) and pregnancy induced
      hypertension (P = 0.029) were observed in metformin treated group. Small for date
      babies were more in metformin group (P < 0.01). Neonatal hypoglycemia was
      significantly less and so was NICU stay of >24 hours in metformin group (P <
      0.01). Significant reduction in cost of treatment was found in metformin group.
      CONCLUSION: Metformin alone or with add-on insulin is an effective and cheap
      treatment option for patients with type 2 diabetes in pregnancy. This trial is
      registered with clinical trial registration number: Clinical trials.gov
      NCT01855763.

PMID- 25874237
TI  - Changes in plasma levels of N-arachidonoyl ethanolamine and N
      palmitoylethanolamine following bariatric surgery in morbidly obese females with
      impaired glucose homeostasis.
AB  - AIM: We examined endocannabinoids (ECs) in relation to bariatric surgery and the
      association between plasma ECs and markers of insulin resistance. METHODS: A
      study of 20 participants undergoing bariatric surgery. Fasting and 2-hour plasma
      glucose, lipids, insulin, and C-peptide were recorded preoperatively and 6 months
      postoperatively with plasma ECs (AEA, 2-AG) and endocannabinoid-related lipids
      (PEA, OEA). RESULTS: Gender-specific analysis showed differences in AEA, OEA, and
      PEA preoperatively with reductions in AEA and PEA in females postoperatively.
      Preoperatively, AEA was correlated with 2-hour glucose (r = 0.55, P = 0.01), HOMA
      IR (r = 0.61, P = 0.009), and HOMA %S (r = -0.71, P = 0.002). OEA was correlated
      with weight (r = 0.49, P = 0.03), waist circumference (r = 0.52, P = 0.02),
      fasting insulin (r = 0.49, P = 0.04), and HOMA-IR (r = 0.48, P = 0.05). PEA was
      correlated with fasting insulin (r = 0.49, P = 0.04). 2-AG had a negative
      correlation with fasting glucose (r = -0.59, P = 0.04). CONCLUSION: Gender
      differences exist in circulating ECs in obese subjects. Females show changes in
      AEA and PEA after bariatric surgery. Specific correlations exist between
      different ECs and markers of obesity and insulin and glucose homeostasis.

PMID- 25874240
TI  - An unjustified prognosis of the number of asbestos-related lung cancer cases
      caused by an increase in airborne asbestos concentrations as a result of removing
      of asbestos-cement products.

PMID- 25874241
TI  - Integrating reconfigurable hardware-based grid for high performance computing.
AB  - FPGAs have shown several characteristics that make them very attractive for high
      performance computing (HPC). The impressive speed-up factors that they are able
      to achieve, the reduced power consumption, and the easiness and flexibility of
      the design process with fast iterations between consecutive versions are examples
      of benefits obtained with their use. However, there are still some difficulties
      when using reconfigurable platforms as accelerator that need to be addressed: the
      need of an in-depth application study to identify potential acceleration, the
      lack of tools for the deployment of computational problems in distributed
      hardware platforms, and the low portability of components, among others. This
      work proposes a complete grid infrastructure for distributed high performance
      computing based on dynamically reconfigurable FPGAs. Besides, a set of services
      designed to facilitate the application deployment is described. An example
      application and a comparison with other hardware and software implementations are
      shown. Experimental results show that the proposed architecture offers
      encouraging advantages for deployment of high performance distributed
      applications simplifying development process. 

PMID- 25874239
TI  - Iodine-131 metaiodobenzylguanidine therapy for neuroblastoma: reports so far and
      future perspective.
AB  - Neuroblastoma, which derives from neural crest, is the most common extracranial
      solid cancer in childhood. The tumors express the norepinephrine (NE)
      transporters on their cell membrane and take in metaiodobenzylguanidine (MIBG)
      via a NE transporter. Since iodine-131 (I-131) MIBG therapy was firstly reported,
      many trails of MIBG therapy in patients with neuroblastoma were performed. Though
      monotherapy with a low dose of I-131 MIBG could achieve high-probability pain
      reduction, the objective response was poor. In contrast, more than 12 mCi/kg I
      131 MIBG administrations with or without hematopoietic cell transplantation (HCT)
      obtain relatively good responses in patients with refractory or relapsed
      neuroblastoma. The combination therapy with I-131 MIBG and other modalities such
      as nonmyeloablative chemotherapy and myeloablative chemotherapy with HCT improved
      the therapeutic response in patients with refractory or relapsed neuroblastoma.
      In addition, I-131 MIBG therapy incorporated in the induction therapy was proved
      to be feasible in patients with newly diagnosed neuroblastoma. To expand more the
      use of MIBG therapy for neuroblastoma, further studies will be needed especially
      in the use at an earlier stage from diagnosis, in the use with other radionuclide
      formations of MIBG, and in combined use with other therapeutic agents. 

PMID- 25874242
TI  - Ubiquitous systems towards green, sustainable, and secured smart environment.

PMID- 25874238
TI  - "New" antigenic targets and methodological approaches for refining laboratory
      diagnosis of antiphospholipid syndrome.
AB  - Antiphospholipid antibodies (aPLs) are a heterogeneous group of antibodies
      directed against phospholipids or protein/phospholipid complexes. Currently, aPLs
      are assessed using either "solid-phase" assays that identify anticardiolipin
      antibodies and anti-beta2-glycoprotein I antibodies or "liquid-phase" assay that
      identifies lupus anticoagulant. However, in the last few years, "new" antigenic
      targets and methodological approaches have been employed for refining laboratory
      diagnosis of antiphospholipid syndrome (APS). In this review the potential
      diagnostic value of antibodies to domains of beta2-GPI,
      prothrombin/phosphatidylserine, vimentin/cardiolipin, protein S, protein C,
      annexin A2, annexin A5, and phospholipid antigens is discussed. Moreover, new
      technical approaches, including chemiluminescence, multiline dot assay, and thin
      layer chromatography (TLC) immunostaining, which utilize different supports for
      detection of aPL, have been developed. A special focus has been dedicated on
      "seronegative" APS, that is, those patients with a clinical profile suggestive of
      APS (thromboses, recurrent miscarriages, or foetal loss), who are persistently
      negative for the routinely used aPL. Recent findings suggest that, in sera from
      patients with SN-APS, antibodies may be detected using "new" antigenic targets
      (mainly vimentin/cardiolipin) or methodological approaches different from
      traditional techniques (TLC immunostaining). Thus, APS represents a mosaic, in
      which antibodies against different antigenic targets may be detected thanks to
      the continuously evolving new technologies. 

PMID- 25874243
TI  - Analgesia evaluation of 2 NSAID drugs as adjuvant in management of chronic
      temporomandibular disorders.
AB  - The aim of this triple-blind full-randomized clinical trial was to quantify
      analgesia in masticatory muscles and temporomandibular joints after occlusal
      splint therapy associated with the adjuvant administration of nonsteroidal anti
      inflammatory drugs (NSAID) isolated or associated with other therapeutic agents.
      Pain relief was also recorded. Eighteen volunteers who had been suffering from
      chronic pain in masticatory muscles due to temporomandibular disorders were
      selected after anamnesis and assessment using RDC/TMD translated to Portuguese.
      The 3 proposed treatments were NSAID (sodium diclofenac), panacea (sodium
      diclofenac + carisoprodol + acetaminophen + caffeine), and a placebo. The total
      treatment duration was 10 days, preceded and succeeded by patients' pain
      assessment. A washout interval of 11 days was established between each therapy.
      All participants received all treatments in different moments, in a full
      randomized crossover methodology. The assessment of drug therapies was performed
      using visual analogue scale for pain on palpation followed by 11-point numerical
      scale to quantify pain during treatment. Statistical analysis has shown that,
      after 10 days of treatment, all therapies were effective for pain relief. NSAID
      therapy promoted analgesia on the third day, while placebo only promoted
      analgesia in the eighth day. It has been concluded that sodium diclofenac used as
      splint adjuvant therapy, promotes significant analgesia in a shorter time. 

PMID- 25874245
TI  - Primary path reservation using enhanced slot assignment in TDMA for session
      admission.
AB  - Mobile ad hoc networks (MANET) is a self-organized collection of nodes that
      communicates without any infrastructure. Providing quality of service (QoS) in
      such networks is a competitive task due to unreliable wireless link, mobility,
      lack of centralized coordination, and channel contention. The success of many
      real time applications is purely based on the QoS, which can be achieved by
      quality aware routing (QAR) and admission control (AC). Recently proposed QoS
      mechanisms do focus completely on either reservation or admission control but are
      not better enough. In MANET, high mobility causes frequent path break due to the
      fact that every time the source node must find the route. In such cases the QoS
      session is affected. To admit a QoS session, admission control protocols must
      ensure the bandwidth of the relaying path before transmission starts; reservation
      of such bandwidth noticeably improves the admission control performance. Many
      TDMA based reservation mechanisms are proposed but need some improvement over
      slot reservation procedures. In order to overcome this specific issue, we propose
      a framework-PRAC (primary path reservation admission control protocol), which
      achieves improved QoS by making use of backup route combined with resource
      reservation. A network topology has been simulated and our approach proves to be
      a mechanism that admits the session effectively. 

PMID- 25874244
TI  - Influence of the Nd:YAG laser pulse duration on the temperature of primary
      enamel.
AB  - The aim of this study is to evaluate the temperature change on specimens of
      primary enamel irradiated with different pulse duration of Nd:YAG laser. Fifteen
      sound primary molars were sectioned mesiodistally, resulting in 30 specimens (3.5
      * 3.5 * 2.0 mm). Two small holes were made on the dentin surface in which K-type
      thermocouples were installed to evaluate thermal changes. Specimens were randomly
      assigned in 3 groups (n = 10): A = EL (extra long pulse, 10.000 MUs), B = LP
      (long pulse, 700 MUs), and C = SP (short pulse, 350 MUs). Nd:YAG laser (lambda =
      1.064 MUm) was applied at contact mode (10 Hz, 0.8 W, 80 mJ) and energy density
      of 0.637 mJ/mm(2). Analysis of variance (ANOVA) was performed for the statistical
      analysis (P = 0.46). Nd:YAG laser pulse duration provided no difference on the
      temperature changes on primary enamel, in which the following means were
      observed: A = EL (23.15 degrees C +/- 7.75), B = LP (27.33 degrees C +/- 11.32),
      and C = SP (26.91 degrees C +/- 12.85). It can be concluded that the duration of
      the laser pulse Nd:YAG increased the temperature of the primary enamel but was
      not influenced by different pulse durations used in the irradiation. 

PMID- 25874246
TI  - A novel multiobjective evolutionary algorithm based on regression analysis.
AB  - As is known, the Pareto set of a continuous multiobjective optimization problem
      with m objective functions is a piecewise continuous (m - 1)-dimensional manifold
      in the decision space under some mild conditions. However, how to utilize the
      regularity to design multiobjective optimization algorithms has become the
      research focus. In this paper, based on this regularity, a model-based
      multiobjective evolutionary algorithm with regression analysis (MMEA-RA) is put
      forward to solve continuous multiobjective optimization problems with variable
      linkages. In the algorithm, the optimization problem is modelled as a promising
      area in the decision space by a probability distribution, and the centroid of the
      probability distribution is (m - 1)-dimensional piecewise continuous manifold.
      The least squares method is used to construct such a model. A selection strategy
      based on the nondominated sorting is used to choose the individuals to the next
      generation. The new algorithm is tested and compared with NSGA-II and RM-MEDA.
      The result shows that MMEA-RA outperforms RM-MEDA and NSGA-II on the test
      instances with variable linkages. At the same time, MMEA-RA has higher efficiency
      than the other two algorithms. A few shortcomings of MMEA-RA have also been
      identified and discussed in this paper. 

PMID- 25874247
TI  - Composition of web services using Markov decision processes and dynamic
      programming.
AB  - We propose a Markov decision process model for solving the Web service
      composition (WSC) problem. Iterative policy evaluation, value iteration, and
      policy iteration algorithms are used to experimentally validate our approach,
      with artificial and real data. The experimental results show the reliability of
      the model and the methods employed, with policy iteration being the best one in
      terms of the minimum number of iterations needed to estimate an optimal policy,
      with the highest Quality of Service attributes. Our experimental work shows how
      the solution of a WSC problem involving a set of 100,000 individual Web services
      and where a valid composition requiring the selection of 1,000 services from the
      available set can be computed in the worst case in less than 200 seconds, using
      an Intel Core i5 computer with 6 GB RAM. Moreover, a real WSC problem involving
      only 7 individual Web services requires less than 0.08 seconds, using the same
      computational power. Finally, a comparison with two popular reinforcement
      learning algorithms, sarsa and Q-learning, shows that these algorithms require
      one or two orders of magnitude and more time than policy iteration, iterative
      policy evaluation, and value iteration to handle WSC problems of the same
      complexity. 

PMID- 25874249
TI  - Chaos time series prediction based on membrane optimization algorithms.
AB  - This paper puts forward a prediction model based on membrane computing
      optimization algorithm for chaos time series; the model optimizes simultaneously
      the parameters of phase space reconstruction (tau, m) and least squares support
      vector machine (LS-SVM) (gamma, sigma) by using membrane computing optimization
      algorithm. It is an important basis for spectrum management to predict accurately
      the change trend of parameters in the electromagnetic environment, which can help
      decision makers to adopt an optimal action. Then, the model presented in this
      paper is used to forecast band occupancy rate of frequency modulation (FM)
      broadcasting band and interphone band. To show the applicability and superiority
      of the proposed model, this paper will compare the forecast model presented in it
      with conventional similar models. The experimental results show that whether
      single-step prediction or multistep prediction, the proposed model performs best
      based on three error measures, namely, normalized mean square error (NMSE), root
      mean square error (RMSE), and mean absolute percentage error (MAPE). 

PMID- 25874248
TI  - CO2 laser and topical fluoride therapy in the control of caries lesions on
      demineralized primary enamel.
AB  - This study evaluated the effect of CO2 laser irradiation and topical fluoride
      therapy in the control of caries progression on primary teeth enamel. 30
      fragments (3 * 3 * 2 mm) from primary canines were submitted to an initial
      cariogenic challenge that consisted of immersion on demineralizing solution for 3
      hours and remineralizing solution for 21 hours for 5 days. Fragments were
      randomly assigned into three groups (n = 10): L: CO2 laser (lambda = 10.6 MUm),
      APF: 1.23% acidulated phosphate fluoride, and C: no treatment (control). CO2
      laser was applied with 0.5 W power and 0.44 J/cm(2) energy density. Fluoride
      application was performed with 0.1 g for 1 minute. Cariogenic challenge was
      conducted for 5 days following protocol previously described. Subsurface Knoop
      microhardness was measured at 30 MUm from the edge. Obtained data were subjected
      to analysis the variance (ANOVA) and Duncan test with significance of 5%. It was
      found that the L group showed greater control of deciduous enamel
      demineralization and were similar to those of APF group, while being
      statistically different from C group (P <= 0.05) that showed the lowest
      microhardness values. It was concluded that CO2 laser can be an additional
      resource in caries control progression on primary teeth enamel.

PMID- 25874250
TI  - A double-sided linear primary permanent magnet vernier machine.
AB  - The purpose of this paper is to present a new double-sided linear primary
      permanent magnet (PM) vernier (DSLPPMV) machine, which can offer high thrust
      force, low detent force, and improved power factor. Both PMs and windings of the
      proposed machine are on the short translator, while the long stator is designed
      as a double-sided simple iron core with salient teeth so that it is very robust
      to transmit high thrust force. The key of this new machine is the introduction of
      double stator and the elimination of translator yoke, so that the inductance and
      the volume of the machine can be reduced. Hence, the proposed machine offers
      improved power factor and thrust force density. The electromagnetic performances
      of the proposed machine are analyzed including flux, no-load EMF, thrust force
      density, and inductance. Based on using the finite element analysis, the
      characteristics and performances of the proposed machine are assessed. 

PMID- 25874252
TI  - Optimal pipe size design for looped irrigation water supply system using harmony
      search: Saemangeum project area.
AB  - Water supply systems are mainly classified into branched and looped network
      systems. The main difference between these two systems is that, in a branched
      network system, the flow within each pipe is a known value, whereas in a looped
      network system, the flow in each pipe is considered an unknown value. Therefore,
      an analysis of a looped network system is a more complex task. This study aims to
      develop a technique for estimating the optimal pipe diameter for a looped
      agricultural irrigation water supply system using a harmony search algorithm,
      which is an optimization technique. This study mainly serves two purposes. The
      first is to develop an algorithm and a program for estimating a cost-effective
      pipe diameter for agricultural irrigation water supply systems using optimization
      techniques. The second is to validate the developed program by applying the
      proposed optimized cost-effective pipe diameter to an actual study region
      (Saemangeum project area, zone 6). The results suggest that the optimal design
      program, which applies an optimization theory and enhances user convenience, can
      be effectively applied for the real systems of a looped agricultural irrigation
      water supply. 

PMID- 25874251
TI  - Insight in the chemistry of laser-activated dental bleaching.
AB  - The use of optical radiation for the activation of bleaching products has not yet
      been completely elucidated. Laser light is suggested to enhance the oxidizing
      effect of hydrogen peroxide. Different methods of enhancing hydrogen peroxide
      based bleaching are possible. They can be classified into six groups: alkaline pH
      environment, thermal enhancement and photothermal effect, photooxidation effect
      and direct photobleaching, photolysis effect and photodissociation, Fenton
      reaction and photocatalysis, and photodynamic effect. 

PMID- 25874253
TI  - A new fuzzy system based on rectangular pyramid.
AB  - A new fuzzy system is proposed in this paper. The novelty of the proposed system
      is mainly in the compound of the antecedents, which is based on the proposed
      rectangular pyramid membership function instead of t-norm. It is proved that the
      system is capable of approximating any continuous function of two variables to
      arbitrary degree on a compact domain. Moreover, this paper provides one
      sufficient condition of approximating function so that the new fuzzy system can
      approximate any continuous function of two variables with bounded partial
      derivatives. Finally, simulation examples are given to show how the proposed
      fuzzy system can be effectively used for function approximation. 

PMID- 25874254
TI  - Evaluation of marginal integrity of four bulk-fill dental composite materials: in
      vitro study.
AB  - OBJECTIVE: The aim of the study was to compare under in vitro conditions marginal
      sealing of 4 different bulk-fill materials composite restorations of class II.
      METHODS: Comparative evaluation concerned 4 composites of a bulk-fill type:
      SonicFill, Tetric EvoCeram Bulk Fill, Filtek Bulk Fill, and SDR. The study used
      30 third molars without caries. In each tooth 4 cavities of class II were
      prepared. The prepared tooth samples were placed in a 1% methylene blue solution
      for 24 h, and after that in each restoration the depth of dye penetration along
      the side walls was evaluated. RESULTS: The highest rating (score 0, no dye
      penetration) was achieved by 93.33% of the restorations made of the SDR material,
      90% of restorations of SonicFill system, 86.66% of restorations of the composite
      Filtek Bulk Fill, and 73.33% of restorations of the Tetric EvoCeram Bulk Fill.
      CONCLUSION: The performed study showed that bulk-fill flowable or sonic-activated
      flowable composite restorations have better marginal sealing (lack of
      discoloration) in comparison with bulk-fill paste-like composite.

PMID- 25874255
TI  - Herbal mouthwash containing extracts of Baccharis dracunculifolia as agent for
      the control of biofilm: clinical evaluation in humans.
AB  - Baccharis dracunculifolia DC (Asteraceae), popularly known as "alecrim-do-campo,"
      is largely distributed in South America, is shown to exhibit protective actions
      against gastric ulcers, has anti-inflammatory properties, and is
      hepatoprotective. Several essential oils obtained from Baccharis species possess
      biological activities, such as antimicrobial and antivirus activities. This
      randomized controlled trial evaluated the efficacy of B. dracunculifolia in the
      reduction of dental biofilm, comparing this natural product with other
      mouthwashes already known in the dental market. In measuring the time after use
      of mouthwash (t = 1), there was no difference between products (P = 0.602); that
      is, subjects in the study had a similar PI after the first use. After one week (t
      = 2), there was no difference between the four products evaluated (P = 0.674),
      so, all research individuals completed the study with a similar reduction in
      dental biofilm between themselves but it was different from initial state
      (Friedman test). It is possible to conclude that B. dracunculifolia had the same
      efficiency of the materials used to oral hygiene in reduction of dental plaque
      and, consequently, prevention of dental caries. Thus, we can consider B.
      dracunculifolia as a good candidate for new material to be implemented in dental
      care. 

PMID- 25874257
TI  - A novel psychovisual threshold on large DCT for image compression.
AB  - A psychovisual experiment prescribes the quantization values in image
      compression. The quantization process is used as a threshold of the human visual
      system tolerance to reduce the amount of encoded transform coefficients. It is
      very challenging to generate an optimal quantization value based on the
      contribution of the transform coefficient at each frequency order. The
      psychovisual threshold represents the sensitivity of the human visual perception
      at each frequency order to the image reconstruction. An ideal contribution of the
      transform at each frequency order will be the primitive of the psychovisual
      threshold in image compression. This research study proposes a psychovisual
      threshold on the large discrete cosine transform (DCT) image block which will be
      used to automatically generate the much needed quantization tables. The proposed
      psychovisual threshold will be used to prescribe the quantization values at each
      frequency order. The psychovisual threshold on the large image block provides
      significant improvement in the quality of output images. The experimental results
      on large quantization tables from psychovisual threshold produce largely free
      artifacts in the visual output image. Besides, the experimental results show that
      the concept of psychovisual threshold produces better quality image at the higher
      compression rate than JPEG image compression. 

PMID- 25874256
TI  - Development of PET and SPECT probes for glutamate receptors.
AB  - L-glutamate and its receptors (GluRs) play a key role in excitatory
      neurotransmission within the mammalian central nervous system (CNS). Impaired
      regulation of GluRs has also been implicated in various neurological disorders.
      GluRs are classified into two major groups: ionotropic GluRs (iGluRs), which are
      ligand-gated ion channels, and metabotropic GluRs (mGluRs), which are coupled to
      heterotrimeric guanosine nucleotide binding proteins (G-proteins). Positron
      emission tomography (PET) and single photon emission computed tomography (SPECT)
      imaging of GluRs could provide a novel view of CNS function and of a range of
      brain disorders, potentially leading to the development of new drug therapies.
      Although no satisfactory imaging agents have yet been developed for iGluRs,
      several PET ligands for mGluRs have been successfully employed in clinical
      studies. This paper reviews current progress towards the development of PET and
      SPECT probes for GluRs.

PMID- 25874258
TI  - Laser teeth bleaching: evaluation of eventual side effects on enamel and the pulp
      and the efficiency in vitro and in vivo.
AB  - Light and heat increase the reactivity of hydrogen peroxide. There is no evidence
      that light activation (power bleaching with high-intensity light) results in a
      more effective bleaching with a longer lasting effect with high concentrated
      hydrogen peroxide bleaching gels. Laser light differs from conventional light as
      it requires a laser-target interaction. The interaction takes place in the first
      instance in the bleaching gel. The second interaction has to be induced in the
      tooth, more specifically in the dentine. There is evidence that interaction
      exists with the bleaching gel: photothermal, photocatalytical, and photochemical
      interactions are described. The reactivity of the gel is increased by adding
      photocatalyst of photosensitizers. Direct and effective photobleaching, that is,
      a direct interaction with the colour molecules in the dentine, however, is only
      possible with the argon (488 and 415 nm) and KTP laser (532 nm). A number of
      risks have been described such as heat generation. Nd:YAG and especially high
      power diode lasers present a risk with intrapulpal temperature elevation up to 22
      degrees C. Hypersensitivity is regularly encountered, being it of temporary
      occurrence except for a number of diode wavelengths and the Nd:YAG. The tooth
      surface remains intact after laser bleaching. At present, KTP laser is the most
      efficient dental bleaching wavelength. 

PMID- 25874259
TI  - Theragnostic imaging using radiolabeled antibodies and tyrosine kinase
      inhibitors.
AB  - During the past decade, the efficacy of new molecular targeted drugs such as
      tyrosine kinase inhibitors (TKIs) and monoclonal antibodies has been proven
      worldwide, and molecular targeted therapies have become the mainstream in cancer
      therapy. However, clinical use of these new drugs presents unexpected adverse
      effects or poor therapeutic effects. Therefore, we require diagnostic tools to
      estimate the target molecule status in cancer tissues and predict therapeutic
      efficacy and adverse effects. Although immunohistochemical, polymerase chain
      reaction (PCR) and fluorescence in situ hybridization (FISH) analyses of biopsy
      samples are conventional and popular for this diagnostic purpose, molecular
      imaging modalities such as positron emission tomography (PET) and single photon
      emission computed tomography (SPECT) are also useful for noninvasive estimation
      of gene and protein expression and drug pharmacokinetics. In this review, we
      introduce new radiolabeled TKIs, antibodies, and their clinical application in
      molecular targeted therapy and discuss the issues of these imaging probes. 

PMID- 25874260
TI  - Evaluation of the esthetic properties of developmental defects of enamel: a
      spectrophotometric clinical study.
AB  - OBJECTIVES: Detailed clinical quantification of optical properties of
      developmental defect of enamel is possible with spectrophotometric evaluation.
      Developmental defects of enamel (DDE) are daily encountered in clinical practice.
      DDE are an alteration in quality and quantity of the enamel, caused by disruption
      and/or damage to the enamel organ during amelogenesis. METHODS: Several clinical
      indices have been developed to categorize enamel defects based on their nature,
      appearance, microscopic features, or cause. A sample of 39 permanent teeth
      presenting DDE on labial surface was examined using the DDE Modified Index and
      SpectroShade evaluation. The spectrophotometric approach quantifies L*
      (luminosity), a* (quantity of green-red), and b* (quantity of blue-yellow) of
      different DDE. CONCLUSIONS: SpectroShade evaluation of the optical properties of
      the enamel defect enhances clinical understanding of severity and extent of the
      defect and characterizes the enamel alteration in terms of color discrepancy and
      surface characterization.

PMID- 25874261
TI  - Synthesis of novel peptide dendrimers PDL-GB2 and PDL-G2.
AB  - Peptide dendrimers are a novel type of macromolecules with precise structure,
      which can be used as drug target vector and controlled-release carrier. So it is
      valuable to study. In this paper, novel peptide dendrimers PDL-GB2 and PDL-G2
      were prepared according to divergent procedure with four-orientation molecule as
      the core and L-lysine as the branch unit. And the structures were identified by
      1HNMR, 13CNMR, MS, and elemental analysis.

PMID- 25874262
TI  - Accurate simulation of MPPT methods performance when applied to commercial
      photovoltaic panels.
AB  - A new, simple, and quick-calculation methodology to obtain a solar panel model,
      based on the manufacturers' datasheet, to perform MPPT simulations, is described.
      The method takes into account variations on the ambient conditions (sun
      irradiation and solar cells temperature) and allows fast MPPT methods comparison
      or their performance prediction when applied to a particular solar panel. The
      feasibility of the described methodology is checked with four different MPPT
      methods applied to a commercial solar panel, within a day, and under realistic
      ambient conditions. 

PMID- 25874263
TI  - An approach to model based testing of multiagent systems.
AB  - Autonomous agents perform on behalf of the user to achieve defined goals or
      objectives. They are situated in dynamic environment and are able to operate
      autonomously to achieve their goals. In a multiagent system, agents cooperate
      with each other to achieve a common goal. Testing of multiagent systems is a
      challenging task due to the autonomous and proactive behavior of agents. However,
      testing is required to build confidence into the working of a multiagent system.
      Prometheus methodology is a commonly used approach to design multiagents systems.
      Systematic and thorough testing of each interaction is necessary. This paper
      proposes a novel approach to testing of multiagent systems based on Prometheus
      design artifacts. In the proposed approach, different interactions between the
      agent and actors are considered to test the multiagent system. These interactions
      include percepts and actions along with messages between the agents which can be
      modeled in a protocol diagram. The protocol diagram is converted into a protocol
      graph, on which different coverage criteria are applied to generate test paths
      that cover interactions between the agents. A prototype tool has been developed
      to generate test paths from protocol graph according to the specified coverage
      criterion. 

PMID- 25874264
TI  - A novel clustering algorithm inspired by membrane computing.
AB  - P systems are a class of distributed parallel computing models; this paper
      presents a novel clustering algorithm, which is inspired from mechanism of a
      tissue-like P system with a loop structure of cells, called membrane clustering
      algorithm. The objects of the cells express the candidate centers of clusters and
      are evolved by the evolution rules. Based on the loop membrane structure, the
      communication rules realize a local neighborhood topology, which helps the
      coevolution of the objects and improves the diversity of objects in the system.
      The tissue-like P system can effectively search for the optimal partitioning with
      the help of its parallel computing advantage. The proposed clustering algorithm
      is evaluated on four artificial data sets and six real-life data sets.
      Experimental results show that the proposed clustering algorithm is superior or
      competitive to k-means algorithm and several evolutionary clustering algorithms
      recently reported in the literature. 

PMID- 25874265
TI  - Conceptual comparison of population based metaheuristics for engineering
      problems.
AB  - Metaheuristic algorithms are well-known optimization tools which have been
      employed for solving a wide range of optimization problems. Several extensions of
      differential evolution have been adopted in solving constrained and
      nonconstrained multiobjective optimization problems, but in this study, the third
      version of generalized differential evolution (GDE) is used for solving practical
      engineering problems. GDE3 metaheuristic modifies the selection process of the
      basic differential evolution and extends DE/rand/1/bin strategy in solving
      practical applications. The performance of the metaheuristic is investigated
      through engineering design optimization problems and the results are reported.
      The comparison of the numerical results with those of other metaheuristic
      techniques demonstrates the promising performance of the algorithm as a robust
      optimization tool for practical purposes. 

PMID- 25874266
TI  - Measuring efficiency and productivity growth of new technology-based firms in
      business incubators: the Portuguese case study of Madan Parque.
AB  - Business incubators can play a major role in helping to turn a business idea into
      a technology-based organization that is economically efficient. However, there is
      a shortage in the literature regarding the efficiency evaluation and productivity
      evolution of the new technology-based firms (NTBFs) in the incubation scope. This
      study develops a model based on the data envelopment analysis (DEA) methodology,
      which allows the incubated NTBFs to evaluate and improve the efficiency of their
      management. Moreover, the Malmquist index is used to examine productivity change.
      The index is decomposed into multiple components to give insights into the root
      sources of productivity change. The proposed model was applied in a case study
      with 13 NTBFs incubated. From that study, we conclude that inefficient firms
      invest excessively in research and development (R&D), and, on average, firms have
      a productivity growth in the period of study. 

PMID- 25874268
TI  - Editorial: Share me and Like me!

PMID- 25874267
TI  - Stochastic control of inertial sea wave energy converter.
AB  - The ISWEC (inertial sea wave energy converter) is presented, its control problems
      are stated, and an optimal control strategy is introduced. As the aim of the
      device is energy conversion, the mean absorbed power by ISWEC is calculated for a
      plane 2D irregular sea state. The response of the WEC (wave energy converter) is
      driven by the sea-surface elevation, which is modeled by a stationary and
      homogeneous zero mean Gaussian stochastic process. System equations are
      linearized thus simplifying the numerical model of the device. The resulting
      response is obtained as the output of the coupled mechanic-hydrodynamic model of
      the device. A stochastic suboptimal controller, derived from optimal control
      theory, is defined and applied to ISWEC. Results of this approach have been
      compared with the ones obtained with a linear spring-damper controller,
      highlighting the capability to obtain a higher value of mean extracted power
      despite higher power peaks. 

PMID- 25874269
TI  - The "hybrid abutment": a new design for implant cemented restorations in the
      esthetic zones.
AB  - Cemented implant restorations are widely used by many dentists. The traditional
      abutment design resembles a natural tooth prepared for a crown with a similar
      taper and a chamfer finish line. A frequent complication associated with implant
      restorations in the esthetic zones is the recession of buccal gingiva over time.
      Abutment morphology, among several other prosthetic factors, may play an
      important role in the stability of the gingival margin in esthetically sensitive
      areas, but this has never been thoroughly analyzed. Recently, a prosthetic
      technique called biologically oriented preparation technique (BOPT) has been
      proposed, which utilizes a feather-edge preparation on natural abutments, and it
      has been claimed that applying the concepts of this technique to implant
      abutments could improve long-term gingival margin stability. At present, there is
      no available evidence to confirm this claim. Moreover, some concerns may arise if
      this particular design is implemented in every clinical situation. With these
      considerations in mind, this article proposes the "hybrid abutment" design (HAD),
      a new design that includes a combination of the two types of features--a feather
      edge on the buccal side, and a chamfer finish line on the lingual side. The
      article also presents a rationale for the use of different abutment designs for
      different situations.

PMID- 25874270
TI  - Evidence-based concepts and procedures for bonded inlays and onlays. Part I.
      Historical perspectives and clinical rationale for a biosubstitutive approach.
AB  - This first article in the series (Part I) aims to present an updated rationale
      and treatment approach for indirect adhesive posterior restorations based on the
      best scientific and long-term clinical evidence available. The proposed treatment
      concept relies on the basic ideas of (1) the placement of an adhesive base/liner
      (Dual Bonding [DB] and Cavity Design Optimization [CDO]) and, when needed, (2) a
      simultaneous relocation of deep cervical margins (Cervical Margin Relocation
      [CMR]), prior to (3) impression taking to ensure a more conservative preparation
      and easier-to-follow clinical steps, and the use of (4) a highly filled, light
      curing restorative material for the cementation (Controlled Adhesive Cementation
      [CAC]), together with restoration insertion facilitation, the application of
      sonic/ultrasonic energy, and/or material heating. The suggested clinical protocol
      will help the practitioner to eliminate the most frequently experienced
      difficulties relating to the preparation, isolation, impression taking and
      cementation of tooth-colored inlays and onlays. This protocol can be applied to
      both ceramics and composites as no material has been proven to be the most
      feasible or reliable in all clinical indications regarding its physicochemical
      and handling characteristics. For the time being, however, we have to regard such
      indirect restorations as a biosubstitution due to the monolithic nature of the
      restoration, with still very imperfect replication of the specific natural dentin
      enamel assemblage.

PMID- 25874271
TI  - The scalpel finishing technique: a tooth-friendly way to finish dental composites
      in anterior teeth.
AB  - Optimal results can be obtained on direct restorations by the application of
      layering procedures that combine the accurate morphological insertion of
      restorative materials with the knowledge of the optical and mechanical properties
      of both composite resin and natural hard dental tissue. Even if the finishing
      procedures on restorations, such as margination (the trimming of margins), are
      minimized by anatomical layering techniques, finishing can still be highly
      complicated due to a number of pre-finishing sequences using specific instruments
      proposed in the literature, which include finishing burs and abrasive discs.
      Finishing procedures performed with a scalpel on polymerized direct composite
      restorations can improve the quality of the final sculptured surface by
      developing natural contours and characteristics and by removing the excess
      restorative material at the tooth-structure margin. Enhanced movement control and
      fine fingertip perception of the surface texture while moving the scalpel blade
      allow the operator to detect and cut the excess composite material during the
      margination procedure and to refine the final anatomy. Avoiding the use of
      finishing burs during finishing procedures on direct composite restorations may
      save adjacent enamel surfaces from abrasive damage. The composite surface and
      margins may also benefit from using the scalpel finishing technique, considering
      the potential risk of excess removal and surface crazing that the improper use of
      finishing burs could cause to composite material. The purpose of this article is
      to propose and describe the scalpel finishing technique step by step, as well as
      to briefly discuss the advantages of its application within the limits of a
      clinical case report. 

PMID- 25874272
TI  - Retrospective survival analysis of 110 lithium disilicate crowns with feather
      edge marginal preparation.
AB  - PURPOSE: To evaluate the clinical performance of lithium disilicate (LiDiSi)
      crowns with a feather-edge finish line margin over a 9-year period. MATERIALS AND
      METHODS: In total, 110 lithium disilicate crowns, 40 anterior (36.3%) and 70
      posterior (63.7%), were cemented with resin cement after fluoridric acid and
      silane surface treatment and observed by a different clinician. The data were
      analyzed using the Kaplan-Meier method. The clinical evaluation used the
      California Dental Association (CDA) modified criteria after recalling all
      patients between January and April 2013. RESULTS: Two crowns had failed and were
      replaced due to core fractures. One chipping occurred on a first molar and the
      ceramic surface was polished. The overall survival probability was 96.1% up to 9
      years, with a failure rate of 1.8%. CONCLUSION: In this retrospective analysis,
      lithium disilicate with a vertical finish line used in single-crown restorations
      had a low clinical failure rate up to 9 years.

PMID- 25874273
TI  - Modified double papillae flap technique: a new surgical approach for the
      treatment of isolated gingival recession defects. A case series.
AB  - AIM: There have been no modifications made to the original double papillae flap
      surgical technique introduced by Cohen and Ross in 1968. The aim of the present
      case series is to evaluate the effectiveness of a modified surgical approach to
      the double papillae flap design in the treatment of isolated gingival recession.
      MATERIALS AND METHODS: A total of 12 healthy, young patients (age range 20 to 28
      years) with isolated gingival recession were enrolled in this study. The gingival
      recession had the following characteristics: isolated defect, Miller Class I or
      II defect, visible cementoenamel junction (CEJ), and well represented interdental
      papillae. The following clinical measurements were taken before the surgery and
      at the 1-year follow-up examination: probing depth (PD) at the treated tooth,
      clinical attachment level (CAL), amount of keratinized tissue (KT) at the treated
      site, and recession depth (RD). All measurements were taken at baseline and after
      12 months by means of a manual probe and were rounded up to the nearest
      millimeter. RESULTS: At the 1-year follow-up examination, the same clinical
      parameters taken at baseline were rerecorded. No statistical differences were
      noted for the PD (P=0.54). The mean increase for the CAL was statistically
      significant (P=0.04). Furthermore, the mean amount of KT increased by 2.5+/-0.4
      mm (P<0.001). Finally, the mean RD decreased to 0.5+/-0.6 mm, corresponding to a
      root coverage of 3.8+/-0.8 mm (P<0.001). In terms of mean root coverage (MRC),
      88.4% of exposed root surface was covered with soft tissue, and 9 of the 12
      treated teeth (75%) showed complete coverage of the root surface. CONCLUSION: The
      results of the present case series show that the modified double papillae flap
      technique is effective in obtaining root coverage of isolated gingival recession
      defects. These rootcoverage outcomes were associated with clinically and
      statistically highly significant clinical attachment gain, with no noticeable
      change in either the PD values or the height of KT on the buccal aspect of the
      treated teeth.

PMID- 25874274
TI  - Surgical-prosthetic management of facial soft tissue defects on anterior single
      implant-supported restorations: a clinical report.
AB  - The surgical correction of soft tissue defects on the facial aspects of dental
      implants is documented as an unpredictable procedure. Since the customization of
      the prosthetic emergence profile contributes significantly to the final esthetic
      outcome of the soft tissue, a combined surgical-prosthetic approach has been
      described in the literature. In the case presented in this article, a
      multidisciplinary approach was used to treat a patient's anterior sextant. It
      included the treatment of a previously placed implant, perfectly osseointegrated,
      with a 2 mm recession of the facial soft tissue. Two connective tissue grafting
      procedures were performed, in conjunction with the modification of the prosthetic
      profile of the provisional restoration and the definitive abutment. The final
      esthetic outcome satisfied the patient and resolved the main complaint, and is
      documented to have been stable for 5 years. 

PMID- 25874275
TI  - Ethnicity and perception of dental shade esthetics.
AB  - AIM AND OBJECTIVES: To determine whether or not people from different ethnic
      backgrounds have different attitudes towards dental esthetics and chose different
      dental appearances in terms of tooth shade, and to determine whether the dental
      professional's choice and the individual's own choice have any relationship with
      what the individual ideally perceives as esthetically pleasing. METHODOLOGY: For
      this cross-sectional analytical study, 120 volunteer students from the University
      of Sheffield (excepting dental students) from various ethnic backgrounds, of
      different ages, of both genders, and with varying degree/educational levels were
      recruited from the campus. The volunteers were asked to complete a questionnaire
      containing 9 adapted attitudinal statements regarding positive or negative dental
      esthetic perceptions in terms of tooth shade, with responses on a 5-point Likert
      scale from "Entirely agree" to "Entirely disagree". Scores for all attitudinal
      statements were summed up to give an attitudinal score. The participants' ideal,
      perceived, and actual (self-assessed and investigatorassessed) tooth shade was
      also determined using a shade guide and a facial mirror. RESULTS: No association
      between ethnicity and attitudinal score was found. However, statistically
      significant associations were found between the participants' degree/educational
      level (P=0.004, 95% Confidence Interval (CI)=-4.18 to -0.82) and their ideal
      tooth shade value (P=0.038, 95% CI=-3.53 to -0.11). There were strong
      correlations between self-assessed and professionally assessed tooth shade value
      in all ethnic groups, with Spearman's rank correlation coefficient (rho) being
      rho>0.6. Regarding ideally desired and perceived tooth shade value, weak
      correlations were found in all ethnic groups (Spearman's rho being rho<0.4).
      CONCLUSION: Although no significant association was found in this sample between
      ethnicity and attitude towards dental esthetics with regard to tooth shade, both
      ethnicity and dental esthetics are very diverse terms with multiple dimensions,
      each of which needs further investigation with regard to their mutual
      association.

PMID- 25874276
TI  - Proceedings of the 10th Closed Meeting of the European Academy of Esthetic
      Dentistry (EAED), Barcelona, October 24-25, 2014.

PMID- 25874277
TI  - Interdisciplinary collaboration: an approach to optimize outcomes for patients
      with compromised dental esthetics.

PMID- 25874280
TI  - Coherent resonance of quantum plasmons in the graphene-gold cluster hybrid
      system.
AB  - Noble metal nanoparticles can modify the optical properties of graphene. Here we
      present a detailed theoretical analysis of the coherent resonance of quantum
      plasmons in the graphene-gold cluster hybrid system by using time dependent
      density functional theory (TDDFT). This plasmon coherent effect is mainly
      attributed to the electromagnetic field coupling between the graphene and the
      gold cluster. As a result, the optical response of the hybrid system exhibits a
      remarkably strong, selectable tuning and polarization dependent plasmon resonance
      enhanced in wide frequency regions. This investigation provides an improved
      understanding of the plasmon enhancement effect in a graphene-based photoelectric
      device. 

PMID- 25874281
TI  - Gas-phase reaction of two unsaturated ketones with atomic Cl and O3: kinetics and
      products.
AB  - The rate constants and products for the reactions of atomic Cl and O3 molecule
      with 3-methyl-3-buten-2-one (MBO332) and 3-methyl-3-penten-2-one (MPO332) were
      determined in a 100 L Teflon chamber at 293 +/- 1 K and atmospheric pressure. For
      MBO332 and MPO332, the rate constants measured with atomic Cl were (2.38 +/-
      0.26) * 10(-10) and (3.00 +/- 0.34) * 10(-10) cm(3) molecule(-1) s(-1) using the
      relative rate method. Using the absolute rate method, the rate constants with O3
      measured were (1.18 +/- 0.21) * 10(-17) and (4.07 +/- 0.45) * 10(-17) cm(3)
      molecule(-1) s(-1). The products of these reactions were investigated by the
      proton-transfer-reaction mass spectrum (PTR-MS). The results indicated that the
      major products observed in the atomic Cl reaction were formaldehyde together with
      chloroacetone for MBO332, and acetaldehyde and CH3C(O)C(O)Cl for MPO332. For O3
      reactions, butanedione and formaldehyde were the main products of MBO332, while
      butanedione and acetaldehyde were the main products of MPO332. Possible reaction
      mechanisms were proposed and discussed and the atmospheric implications of these
      reactions were also discussed. 

PMID- 25874282
TI  - Imprisonment of opioid-dependent people in New South Wales, Australia, 2000-2012:
      a retrospective linkage study.
AB  - There are few data about the incarceration of opioid-dependent people involving
      large representative cohorts. We aimed to determine the prevalence and duration
      of incarceration in a large cohort of opioid-dependent people in Australia using
      data linkage methods, and estimate the costs associated with their
      incarceration.Method: Retrospective linkage study of all entrants to opioid
      substitution therapy (OST) for the treatment of opioid dependence in NSW, 1985
      2010, with data on incarceration, 2000-2012. The number and duration of
      incarcerations were calculated. The average daily cost of incarceration was
      applied to days of incarceration in the cohort.Results: Among 47,196 opioid
      dependent people, 37% (43% of men and 24% of women) had at least one episode of
      incarceration lasting one or more days. Men had a median of three(ranging between
      1-47) incarcerations, and women, two (1-35). Indigenous men spent 23% of follow
      up time incarcerated, compared with 8% for non-Indigenous men; similarly,
      Indigenous women spent a substantially greater proportion of time incarcerated
      than non-Indigenous women (8% vs. 2%). Costs of incarceration of this cohort
      between 2000 and 2012 totalled nearly AUD $3 billion.Conclusions: This is the
      first study to examine incarceration of opioid-dependent people across an entire
      population of such users. Our findings suggest that a substantial minority of
      opioid-dependent people experience incarceration, usually on multiple occasions
      and at significant cost. Treatment for opioid dependence, inside and outside
      prisons, may help reduce incarceration of this cohort.

PMID- 25874283
TI  - Interfaces against pollution 2014: from fundamental to applied environmental
      physical chemistry.

PMID- 25874284
TI  - Bertram E. Bromberg, D.D.S., M.D. 1918 to 2014.

PMID- 25874285
TI  - Psychiatric nursing: an unpopular choice.
AB  - Research studies in the United States, the United Kingdom, New Zealand and
      Australia suggest that students do not consider psychiatric nursing as a popular
      career option. According to this research, there is a widespread concern about
      the nursing shortages in psychiatry. The demand for mental health services
      continues to grow and there is a need for strategies to recruit nurses for this
      specialized field. The purpose of this study was to identify the factors
      preventing undergraduate nursing students in South Africa (SA) from choosing
      psychiatric nursing as a career. A qualitative research design that aimed to
      explore and describe was used. Data were collected through the Nominal Group
      Technique. A sample of convenience of 27 final year nursing students from the
      School of Nursing at the University of the Free State as well as the Free State
      School of Nursing, situated in Bloemfontein (SA), voluntarily participated in
      this research. The following categories emerged from the content analysis of the
      data: personal factors, working environment, unprofessional behaviour, learning
      environment and the unclassified category. Psychiatric nursing as a career choice
      is in a predicament and nursing schools need to implement practical strategies to
      recruit future nurses for this field.

PMID- 25874286
TI  - [In vivo "editing'' of cellular genome: one more step toward animals models
      mimicking tumorigenesis].

PMID- 25874287
TI  - [Carfilzomib in multiple myeloma relapses].

PMID- 25874288
TI  - [Endoscopy in general and visceral surgery - swansong or prospect for the
      future?].

PMID- 25874289
TI  - [Scoliotic spine deformity in children and adolescents associated with the
      craniovertebral junction pathology].
AB  - This literature review is devoted to the clinical and pathogenic aspects of the
      relationship between Chiari type I malformation (CMT) and scoliosis. The view of
      the clinical presentation development in CMT associated with scoliosis is
      considered on the basis of both the CSF dynamics disturbances and vascular
      pathology of the craniovertebral junction. The role of the posterior atlanto
      occipital membrane is evaluated. Case reports of the risk factors for scoliosis
      progression in patients with CMT are presented.

PMID- 25874290
TI  - New guideline for the reporting of studies developing, validating, or updating a
      prediction model.

PMID- 25874291
TI  - [Modern molecular approaches to diagnosis and treatment of high-grade brain
      gliomas].
AB  - The review analyzes the current state of the problem of diagnosis and therapy of
      high-grade gliomas on the basis of the most promising present-day approaches. The
      diagnostic and treatment perspectives of the molecular genetic analysis of
      glioblastoma markers located on the tumor cell surface are considered. Gene
      therapy and the use of dendritic cells and oncolytic viruses are considered as
      the most interesting approaches to therapy of high-grade gliomas.

PMID- 25874292
TI  - [Penetrating head and brain injuries with nonmetal foreign bodies].
AB  - Penetrating brain injuries (PBI) are common in neurosurgical practice. Most of
      them are civil or war-time missile and blast injuries. This type of trauma is
      widely presented in neurosurgical publication, textbooks and clinical evidence
      based guidelines. At the same time, PBI by non-metallic foreign bodies are very
      rare. All the data are limited to case reports and small series of cases.
      Moreover, there are no clinical consideration on diagnosis, treatment,
      complication, outcome and prognosis of PBI by non-metallic penetrating brain
      injuries. In this review all the data are summarized to provide recommendations
      on the diagnosis and treatment of PBI by non-metallic foreign bodies.

PMID- 25874293
TI  - Genome editing as a tool toward better functional understanding of variants
      identified by next-generation sequencing.

PMID- 25874294
TI  - [Physician malpractice - "minor fault" or "gross error?"? Deciding factors].

PMID- 25874295
TI  - [Prevalence of late complications and survival of patients undergoing cardiac
      transplantation: a single-center experience].
AB  - INTRODUCTION: Heart transplantation is the treatment of choice in severe heart
      failure despite maximal medical therapy, which has no other surgical alternatives
      and exhibiting no contraindications. The aim of this study was to analyze the
      prevalence of late complications and survival of patients undergoing cardiac
      transplantation at our Hospital Center. METHODS: We evaluated 78 patients (mean
      age 43 +/- 15 years) transplanted at our center between February 1987 and
      December 2011, with a mean follow-up of 6 years. RESULTS: Of late complications
      after heart transplantation, allograft vascular disease was detected in 10
      patients ( 12.8%), was the one with impact on mortality, being responsible for
      four deaths. The most frequent complication was hypertension in 54.6% of cases,
      followed by dyslipidemia (47.4%), renal failure (47.4%), diabetes mellitus
      (21.8%) and neoplasms (11.5%). Atrial tachyarrhythmias was observed in eight
      patients (10.3%). The overall survival of our population at first and tenth year
      after heart transplantation was 81% and 69%, respectively. The mean survival of
      patients was 15.6 years (Cl 95%: [12,6-18,7]).. There were 23 deaths (29.5%),
      nine (11.5%) of which occurred within the first 30 days after transplantation.
      CONCLUSION: Cardiac transplantation remains a valid therapeutic option for
      patients with end-stage heart disease. Our center had a heart transplant survival
      rate and incidence of late complications similar to those seen in international
      registries.

PMID- 25874296
TI  - [The experience of applying system of continuous monitoring of content of glucose
      in children with glycogen disease].
AB  - The sampling included 23 children with glycogen disease. All patients were
      examined using system of continuous monitoring of content of glucose applied
      during 72 hours. It was established that hypoglycemia was detected in 19 (82.6%)
      children. At that, in 7 (30.4%) children the level of glucose was below detected
      range (< 2.2 mmol/l). In patients ignoring proposed recommendations (lack of
      compliance) expression of hypoglycemia was reliably higher than in children being
      on a diet and following recommendations of physician. In primary patients as
      compared with secondary patients rate and duration of hypoglycemia in blood serum
      activity of aspartate aminotransferase also was reliably higher. Independently of
      all that, the more frequently hypoglycemia developed the more expressed
      hypoglycemia was. Therefore, continuous monitoring of content of glucose in
      intercellular fluid is an effective instrument for detecting degree of
      compensation of carbohydrate metabolism in patients with glycogen disease. The
      day continuous monitoring of level of glucose permits to provide the most
      complete picture of fluctuations of glycaemia during a day. The obtained data can
      be used as a basis for composing an optimal algorithm of diet therapy.

PMID- 25874297
TI  - [The titration of double bonds in fatty acids of blood plasma in patients in
      testing of glucose tolerance].
AB  - The article deals with per oral glucose tolerance test applied to 20 patients
      with arterial hypertension. The blood plasma was analyzed to detect content of
      individual fatty acids, double bounds, glucose, insulin and metabolites of fatty
      acids. In patients with different resistance to insulin content of non-etherized
      fatty acids decreased approximatively up to 3 times. Without insulin resistance
      secretion of insulin in 2 hours after glucose load increased up to 3 times and
      content of individual fatty acids decreases in greater extent. Under insulin
      resistance secretion of insulin increases up to 8 times and decreasing of content
      of fatty acids is less expressed. The decrease in blood plasma of content of
      oleic and linoleic fatty acids and double bounds reflects effectiveness of effect
      of insulin--blockade of hydrolysis of triglycerides in subcutaneous adipocytes.
      The concentration of insulin positively correlates with initial content of
      palmitic fatty acid in the pool of lipids of blood plasma.

PMID- 25874298
TI  - [The lipid peroxidation processes in males with chronic mono trichomonal
      infection against the background of intake of triethanolammonium salt of 2-methyl
      phenoxiacetic acid].
AB  - The research center of problems of family health and human reproduction, Irkutsk,
      Russia The article presents the results of evaluation of processes of lipid
      peroxidation and anti-oxidant defense in males with chronic mono trichomonal
      infection against the background of intake of triethanolammonium salt of methyl
      phenoxiacetic acid, pharmaceutical of phytohormones class with anti-oxidant
      characteristics. The sampling for examination consisted of 61 males with chronic
      urogenital trichomoniasis. The blood plasma and hemolysate prepared from
      erythrocytes were used as material for biochemical analysis. The modern
      spectrophotometric, fluorometric and statistical method of analysis were applied.
      In examined patients the parameters characterizing significant disorders of
      metabolic homeostasis were analyzed. The condition of lipids peroxidation was
      judged by blood concentration of substrates with saturated double bounds, diene
      conjugates, tiobarbituric acid active products expressed in micromol per 1 liter.
      The intensity of processes of anti-oxidant defense was evaluated by content of
      concentrations of alpha-tokopherol and retinol, oxidated and reduced glutathione
      and by activity of super oxide dismutase too. The common anti-oxidant activity of
      blood was measured as indicator characterizing sum total of inhibitors of lipid
      peroxidation and determining its buffer capacity. The reduction of balance in the
      system pro-oxidant-anti-oxidant in direction to anti-oxidant components is marked
      in group of patients with chronic mono trichomonal infection after complex
      treatment including as add-on to common therapy triethanolammonium salt of 2
      methyl phenoxiacetic acid. The effectiveness of complex therapy in many instances
      depends on degree of defense of structure and function of cellular membranes.
      Therefore, application of this pharmaceutical is appropriate because of
      decreasing of level of lipid peroxidation, increasing of anti-oxidant defense of
      organism and normalizing of particular parameters of spermatogenesis.

PMID- 25874299
TI  - [The informative laboratory biomarkers for detection of negative impact of
      vibration on organism of workers].
AB  - The analysis was carried out concerning new characteristics of diagnostic
      informativeness of particular biochemical, immunologic, cytochemical and
      hematologic indicators under impact of vibration on human organism. It is
      established that high diagnostic informativeness is typical for indicators of
      oxidation metabolism (alpha-superoxide dismutase, myeloperoxidase in neutrophils,
      alpha-tokopherol), humoral immunity (IgA, IgG), hematologic indicators
      (corpuscular volume, peroxide hemolysis of erythrocytes, thrombocytes aggregation
      velocity) and level of creatinine in urine reflecting damages of muscular tissue.
      The levels of biomarkers mentioned above begin to alter in healthy workers and in
      individuals under suspicion of vibration disease. These indicators are
      characterized by high diagnostic sensitivity and pathognomonicity and can be
      recommended for early diagnostic of vibration disease.

PMID- 25874300
TI  - [The pharmacokinetics of colistin under parenteral injection of sodium
      colistimitate in children with chemically induced neutropenia].
AB  - The prevalence of hospital strains of P. aeruginosa, A. baumannii and K.
      pneumoniae characterizing by multiple drug resistance to overwhelming majority of
      antibiotics anew evoked an increased interest to colistin. However, until now
      there is not enough information concerning pharmacokinetics of colistin to
      optimize dosage of this pharmaceutical. The study was carried out to analyze
      pharmacokinetics of both colistin and sodium colistimitate in children with
      chemically induced neutropenia. To quantitatively detect colistin in blood serum
      the technique of highly effective fluid chromatography with mass spectrometry was
      applied. The concentration of colistin was detected in 21 children with
      chemically induced neutropenia (13 patients with septicemia, 8 children of
      control group) after intravenous injection of sodium colistimitate. The
      significant variability of pharmacokinetic parameters of colistin was established
      both in patients with septicemia and in control group. The technique of highly
      effective fluid chromatography with mass spectrometry can be applied for
      therapeutic medicinal monitoring and optimization regimen of dosage.

PMID- 25874301
TI  - [The contamination under polymerase chain reaction studies: problems and
      solutions].
AB  - The study was carried out to determine risk factors of false positive and false
      negative results under polymerase chain reaction-analysis of clinical material.
      The samples with high viral load can be the source of false positive results. The
      contamination with nucleic acids can occur at any section of polymerase chain
      reaction analysis. The study data permitted to establish that the most sensitive
      stage is isolation and purification of nucleic acids especially under manual mode
      of operation. The detection of positive signal in most samples of one setting
      indicates total contamination. The cases when only several samples are polluted
      are special challenge. The presence of sample with high concentration of viral
      nucleic acid and several samples with low concentration in one setting means
      necessity of repeated analysis beginning with stage of isolation of nucleic acid.
      The analysis of curves of accumulation of products of amplification, their forms
      and positioning on chart is the obligatory stage of polymerase chain reaction
      study in real time regimen. These actions permit to exclude the readouts of false
      negative testing results to departments. The study conclusions are equipotent for
      polymerase chain reaction testing of any nucleic acid targets.

PMID- 25874302
TI  - [The alternative view on diagnostic of hyperlipoproteinemia, cholesterol
      lipoproteins of low density and effect of statins: a lecture].
AB  - The effect of statins occur in several stages: 1) inhibition in hepatocytes of
      synthesis of functionally specific pool of spirit cholesterol, polar mono-layer
      of lipoproteins of very low density; 2) activation of hydrolysis of triglycerides
      in lipoproteins of very low density, formation of apoE/B-100-ligand and
      absorption of lipoproteins of very low density by insulin-depended cells; 3)
      decreasing of content of and spirit cholesterol-lipoproteins of very low density
      in blood plasma; 4) activation of hydrolysis of triglycerides in lipoproteins of
      low density, formation of apoB-100-ligand and absorption of lipoproteins of low
      density by insulin-independent cells; 5) decreasing of level of and increasing of
      content of lipoproteins of high density. During first weeks of effect of statins
      occurs decreasing of concentration of triglycerides and unesterified spirit
      cholesterol-lipoproteins of very low density in blood plasma. Then, slower and
      more durational decreasing of level of spirit cholesterol-lipoproteins of low
      density occurs. The value of spirit cholesterol-lipoproteins of low density is
      primarily determined by content of palmitic saturated fatty acid in food, its
      endogenous synthesis from glucose and concentration of palmitic triglycerides and
      lipoproteins of very low density of the same name in blood plasma. The effect of
      preparations is biologically valid and corresponds to alternative hypolipidemic
      preparations. All these preparations have an effect following a common algorithm:
      they activate, using different mechanisms, receptor absorption of lipoproteins of
      very low density or lipoproteins of low density by cells. The level of spirit
      cholesterol-lipoproteins of low density in full measure depends on content of
      triglycerides in blood. The concentration of spirit cholesterol in blood plasma
      has a reliable diagnostic significance only under physiological content of
      triglycerides. The main criterion of diagnostic and control of hypolipidemic
      therapy biologically is content of triglycerides. The comprehension of
      differences in effect of hypolipidemic preparations within framework of common
      algorithm permits rationally combine them under treatment of both primary
      inheritable phenotypes of glucolipoproteins and secondary symptomatic types of
      glucolipoproteins under obligatory observation of strict dietary treatment.

PMID- 25874303
TI  - [The organization of centralized testing of donor blood for infection in the
      Irkutskaia oblast].
AB  - The article presents the results of changes of concentration of DNA of viral
      hepatitis B under conservation in frozen conditions. The optimal scheme of
      preparing and delivering samples of donor blood stored up in institutions of
      blood service of the Irkutskaia oblast for molecular biological testing was
      elaborated.

PMID- 25874304
TI  - [The identification of clinical strains Pseudomonas fulva using techniques of
      MALDI-TOF mass spectrometry and common analysis].
AB  - The technique MALDI-TOF mass spectrometry was applied using device Microflex with
      database MALDI Biotyper (Bruckeer Daltonics Inc.) to identify with high level of
      reliability 8 strains P. fulva from collection of pseudo monads isolated from
      clinical material in St. Petersburg. When analyzing the same strains applying
      technique MALDI TOF mass spectrometry using device Vitek MS (bioMerieux) these
      starins were wrongly identifies as P. putida. The complex of tests of common
      analysis was approved and proposed for control differentiation of P. fulva and P.
      putida. The medical significance of P. fulva was approved.

PMID- 25874305
TI  - [The problems of laboratory diagnostic of rickettsiosis of group spotted tick
      bite fever in Russia].
AB  - The article presents analysis of modern techniques of laboratory diagnostic of
      rickettsiosis of spotted tick-bite fever group. Owing to drastic shortage of list
      of produced preparations and increasing of specter of detected types of
      rickettsia in Russia the new approaches to laboratory verification of diagnoses
      are needed. To detect antibodies to rickettsia of spotted tick-bite fever group
      can be recommended such techniques as reaction of indirect immune fluorescence
      and immune enzyme assay with antigens of corresponding types of rickettsia. The
      most acceptable techniques for detecting and identifying rickettsia of spotted
      tick-bite fever group are polymerase chain reaction restricting analysis and
      polymerase chain reaction sequence analysis. The biological methods of analysis
      are needed to study pathogenic types of rickettsia.

PMID- 25874306
TI  - [The detection of occurrence rate of genes coding capability to form pili binding
      in auto-strains of Escherichia coli].
AB  - E. coli is a commensal of intestine of the vertebrata. The exchange of genetic
      material of different types of bacteria between themselves and with other
      representatives of family of Enterobacteriaceae in intestinal ecosystem results
      in development of types of normal colibacillus with genetic characteristics of
      pathogenicity that can serve as a theoretical substantiation to attribute such
      strains to pathobionts. The entero-pathogenic colibacillus continues be an
      important cause of diarrhea in children in developing countries. The gene
      responsible for formation of pili binding is a necessary condition for virulence
      of entero-pathogenic colibacillus. The polymerase chain reaction was applied to
      examine 316 strains of different types of E. coli (normal, with weak enzyme
      activity and hemolytic activity) isolated from healthy children and children with
      functional disorders of gastro-intestinal tract for presence of genes coding
      capability to form pill binding. The presence of this gene in different
      biochemical types of E. coli permits to establish the fact of formation of
      reservoir of pathogenicity in indigent microbiota of intestinal biocenosis.

PMID- 25874307
TI  - [The detection of activity of components and factors of complement according its
      effect on infusorians].
AB  - The article considers the developed techniques of detection of functional
      activity of components C1, C2, C3, C4 and membrane attacking complex of classical
      pathway and also factors B and D of alternative pathway of human complement using
      automated device measurement of immobilizing effect on infusorians Tetrahymena
      pyriformis. The techniques are based on application of artificially produced
      reagents containing all necessary components of compliment besides testing one.
      The mathematical mode of activities calculation is developed. The linear
      dependency of velocity of infusorians immobilizing from functional activities of
      testing component. The relevance of techniques is demonstrated by correlation of
      results derived using the proposed mode with the developed earlier hemolytic
      mode.

PMID- 25874308
TI  - [The analytical quality and comparability value of four glucometers from
      different manufacturers].
AB  - The modern laboratory medicine provides observation of requirements to
      glucometers in line with standard DIN EN ISO 15197-2:2013 for self-control under
      treatment of patients with diabetes mellitus and registration of biologic types
      data. The study compared functioning of diagnostic devices in point-of-care of
      four manufacturers. The samples of whole blood taken from two patients were
      analyzed in three lots of test-strips with concentration of glucose 4.5 and 11.8
      mmol/l using glucometers Accu-Chek Active, One Touch Select, Sattelite Express
      and Contour TS and reference analyzer Olympus AU 400. The results of measurements
      were analyzed using technique of separated test of patient. The results
      demonstrated that precision indicators of measurement of blood glucose on
      glucometers Accu-Chek Active and One Touch Select were within the scope of
      quality criteria DIN EN ISO 15197-2:2013. The results of testing of glucometer
      Sattelite Express exceeded the given criteria under measurement of normoglycemic
      level of concentration and for Contour TS in all range of measured values.

PMID- 25874309
TI  - [Memory of Alexandra Sergeevna Petrova].

PMID- 25874310
TI  - [The definition of a failure to render assistance to the patient in the forensic
      medical practice].
AB  - The authors consider the necessity of determining the severity of harm inflicted
      to human health by the inaction of the officials and other persons responsible
      for rendering assistance to a patient in accordance with article 124 of the
      Criminal Code of the Russian Federation. The absence of the normative formulation
      of the forensic medical criteria for the assessment of the degree of the harm to
      human health as a result of inaction of the subjects responsible for rendering
      medical aid creates difficulties for the enforcement of article 124 of the
      Criminal Code of the Russian Federation in its present wording. This problem
      awaits further studies for the possible adoption of the uniform normative and
      regulatory documents for the consistent application of the definition of inaction
      with reference to the assessment of not rendering medical assistance.

PMID- 25874311
TI  - [The classifying criteria for the evaluation of the severity of the harm to
      health in the case of development of psychic health problems associated with HIV
      infection].
AB  - The objective of the present study was to develop the classifying criteria for
      the evaluation of the severity of the harm inflicted to human health that
      resulted in the development of mental disorders in response to subsequent HIV
      infection. The analysis of the available information about a rise in the
      prevalence of HIV infection and the high frequency of associated psychic
      disorders among the infected subjects gave evidence of the importance of this
      problem and the necessity to improve the existing statutory and legislative basis
      underlying the regulation of activities in this field. The scientifically
      substantiated criteria for the expert assessment of the severity of the harm to
      human health are proposed taking into consideration the clinical manifestations
      of psychic disorders.

PMID- 25874312
TI  - [About the possibility to detect the fact of corpse transportation from the sea
      coastline with the subsequent burial].
AB  - The objective of the present work was to detect and describe the new features
      characterizing the long-term stay of a corpse in seawater followed by its burial
      on earth. The bones of the skeletonized corpse were found to be covered with
      mussels and petrified sea worms that can serve as the indicators of staying the
      corps in seawater and its subsequent transportation from the sea coastline to the
      inland. These findings can be used to clarify the circumstances of death of the
      people found in the illegal burial places at the seacoast of maritime areas.

PMID- 25874313
TI  - [Some histological criteria for the renal and hepatic lesions in the case of
      death from acute intoxication with ethyl alcohol].
AB  - The objective of the present study was to evaluate the results of the microscopic
      studies of acute intoxication with ethyl alcohol at the territory of the
      Udmurtian Republic during the period from 2003 till 2013. A total of 5941 cases
      of death caused by acute intoxication with ethyl alcohol were documented among
      both men and women, largely able-bodied ones. Concentration of ethyl alcohol in
      their blood corresponded to the one known to result in severe or lethal
      intoxication, The forensic histological study of the available tissue samples
      gave evidence of vascular disturbances, enhanced permeability of the vascular
      walls, dystrophic changes in the internal organs, the signs of necronephrosis,
      and concomitant disorders. Epithelium of renal tubules obtained from 0.4% of the
      corpses contained the pigment particles of different structure and colour; other
      pathological changes included cholestasis, necrosis of hepatocytes, various
      lesions and injuries. Similar alterations were identified in the detoxificating
      organs of the subjects who had died from causes other than acute intoxication
      with ethyl alcohol. These findings suggest disturbances of pigment metabolism and
      make it possible to elucidate the peculiar features of patho- and tanatogenesis.

PMID- 25874314
TI  - [The role of surrogate alcoholic beverages in the development of hemorrhage in
      the patients presenting with Mallory-Weiss syndrome].
AB  - The objective of the present work was to study the pathological changes in
      various organs and tanatogenesis associated with Mallory-Weiss syndrome making
      use of the forensic medical and clinical materials. It was shown that the main
      cause of unrestrained vomiting resulting from alcoholic intoxication and leading
      to perfusive bleeding is not only the direct action of ethanol and surrogate
      alcohol on gastroesophageal mucosa and induced thrombocytopenia. Another cause
      may be brain oedema with subsequent cerebral herniation and irritation of the
      pseudobulbar centres responsible for the initiation of the vomiting reflex. The
      authors propose recommendations for forensic medical diagnostics of the cases of
      such hemorrhage.

PMID- 25874315
TI  - [The modern non-invasive methods for the evaluation of the age-specific changes
      in the skin].
AB  - The present review article is designed to analyse the current state-of-the-art in
      the field of diagnostics of the main morphological and functional parameters
      characterizing the involutional processes in the facial skin. The possibilities
      of the practical application of the available non-invasive methods for the
      evaluation of the age of the living people in the framework of the forensic
      medical identification expertise are considered. The main problems and vectors of
      the further development of methodological approaches to the determination of the
      biological age based on the results of the studies of skin and its appendages are
      discussed.

PMID- 25874316
TI  - [The determination of amitriptyline and its metabolite, nortriptyline, in the
      biological objects of the corpse by the high-performance liquid chromatography
      technique].
AB  - Tricyclic antidepressants are among the preparations that most frequently cause
      intoxication in adults and children; moreover, poisoning with these substances
      not infrequently has a fatal outcome. Medications belonging to this group, such
      as amitriptyline, are extensively used to manage manifestations of depression,
      anxiety, migraine, neuropathic pain, and hyperactivity syndrome. Amitriptyline
      overdosage causes non-specific symptoms of intoxication, and its clinical picture
      does not allow to identify the nature of a psychotropic xenobiotic. Of primary
      importance in connection with this is to establish the cause of intoxication or
      death by the clinical toxicological and forensic medical methods based on the
      results of the fast identification and quantitation of amitriptyline in
      biological materials including blood, urine, hepatic tissues, etc. The authors
      describe the method for the determination of amitriptyline and its principal
      physiological metabolite nortriptyline in biological objects with the help of
      high performance liquid chromatography (HPLC).

PMID- 25874317
TI  - [Lethal intoxication with baclofen].
AB  - The objective of the present study was to select and develop simpler methods for
      the quantitative determination of baclofen in blood with the use of HPLC and
      tandem MS (MS-MS) techniques and its qualitative determination in cadaveric
      organs by the GC/MS technique. These mathods were shown to be suitable for the
      purpose of forensic medical analysis, clinical, toxicological, and therapeutic
      monitoring. The special emphasis is laid on the methods used to investigate the
      biological materials obtained from the subjects who died from baclofen
      intoxication.

PMID- 25874318
TI  - [The investigation into specific features of the distribution of carbofuran in
      the body of the warm-blooded animals].
AB  - The objective of the present study was to estimate the distribution of the
      carbamate pesticide carfbofuran in the organism of the warm-blooded animals
      (rats) after its intragastric administration. It was shown that large amounts of
      unmetabolized carbofuran were present in the internal organs and biological
      fluids. The highest content of carbofuran was recorded in the stomach, large and
      small intestines, testicles, urinary bladder, ureters, and heart.

PMID- 25874319
TI  - [The application of the Bayes-Wald-Gubler method for differential diagnostics of
      the causes of death at low environmental temperature].
AB  - The authors propose a modification of the Bayes-Wald-Gubler mathematical method
      designed for differential diagnostics that extends the possibilities of computer
      assisted calculations and simplifies their performance. The practical application
      of the proposed modification is illustrated by differential diagnostics of the
      causes of death at low environmental temperature including lethal hypothermia,
      sudden death from cardiac diseases, mechanical asphyxia, mechanical injury, and
      acute alcoholic intoxication. The most informative histological features are
      described and diagnostic coefficients are presented. The method of calculations
      in the framework of the Microsoft Excel software package are proposed. The
      results obtained with the help of the standard and modified Bayes-Wald-Gubler
      mathematical method are compared, their effectiveness for the purpose of combined
      diagnostics of the causes of death is demonstrated.

PMID- 25874320
TI  - [The method for the postmortem verification of ventricular fibrillation as a
      mechanism of death from myocardial infarction and post-infarction
      cardiosclerosis].
AB  - The objective of the present study was to develop the objective method for the
      verification of death from ventricular fibrillation (VF) as a complication of
      myocardial infarction and post-infarction cardiosclerosis (PICS). A total of 20
      cases of death during different periods after myocardial infarction and PICS were
      available for the analysis in which EGC-confirmed ventricular fibrillation was
      the immediate cause of the fatal outcome. The control group was comprised of 29
      cases of death from other complications. The special emphasis was laid on the
      investigation of the affected region, the boundary areas, and intact zones of the
      heart. The size of cardiac cell populations surrounding capillaries was
      determined. The statistical treatment of the results of the study revealed the
      difference in the cellular infiltrate composition between the groups of patients
      who had died from ventricular fibrillation and other causes. The differences were
      largely reduced to the number of lymphocytes, neutrophils, and leukocytes. The
      data thus obtained provided a basis for the development of the method for the
      objective postmortem verification of the complication being considered.

PMID- 25874321
TI  - [Building questions in forensic medicine and their logical basis].
AB  - The authors characterize in brief the requirements to the correct formulation of
      the questions posed to forensic medical experts with special reference to the
      mistakes made in building the questions and the ways to avoid them. This article
      actually continues the series of publications of the authors concerned with the
      major logical errors encountered in expert conclusions. Further publications will
      be dedicated to the results of the in-depth analysis of the logical errors
      contained in the questions posed to forensic medical experts and encountered in
      the expert conclusions.

PMID- 25874322
TI  - [Forensic medical diagnosis and conclusions in the case of nose bone fracture
      with blood aspiration into the respiratory tract].
AB  - The authors consider the variants of the formulation of forensic medical
      diagnosis and expert conclusions in the cases of death among the victims of nasal
      bone fractures and blood aspiration proposed by different researchers. They
      emphasize the inadmissibility of the formal logical approach in such situations
      and the necessity of pathogenetic analysis of each concrete case for the
      elucidation of nosological forms and syndromes responsible for the fatal outcome.

PMID- 25874323
TI  - [Evgenii Ventseslavovich Pelikan. On the occasion of the 150th anniversary of the
      journal "Arkhiv sudebnoy meditsiny and obshchestvennoy gigieny (Archive of
      forensic medicine and public hygiene)"].
AB  - This article is devoted to the life and multi-faceted activities of Evgeniy
      Ventseslavovich Pelikan, a physician, administrator, and the founder of the first
      Russian journal of forensic medicine.

PMID- 25874324
TI  - [In memory of Oksana Yur'evna Skrebkova].

PMID- 25874325
TI  - [Scientific and practical conference of the young scientists--forensic medical
      experts and pathologoanatomists of the Central federal district "The modern
      methods of laboratory and instrumental diagnostics of the injuries and diseases.
      Prophylaxis of occupational pathology in specialists". Moscow, October 24, 2014].

PMID- 25874326
TI  - Discovery and preliminary evaluation of 2-aminobenzamide and hydroxamate
      derivatives containing 1,2,4-oxadiazole moiety as potent histone deacetylase
      inhibitors.
AB  - Using Entinostat as a lead compound, 2-aminobenzamide and hydroxamate derivatives
      have been designed and synthesized. The entire target compounds were investigated
      for their in vitro antiproliferative activities using the MTT-based assay against
      five human cancer cell lines including U937, A549, NCI-H661, MDA-MB-231 and
      HCT116. 2-Aminobenzamide series of compounds (10a-10j) demonstrated the most
      significant inhibition against human acute monocytic myeloid leukemia cell line
      U937, but no or poor activities against two human lung cancer cell lines.
      Furthermore, the target compounds were screened for their inhibitory activities
      against HDAC 1, 2, and 8. 2-Aminobenzamide derivatives (10) manifested a higher
      selectivity for HDAC 1 over HDAC 2, but were not active against HDAC 8. In
      contrast, most hydroxamate derivatives (11) inhibit HDAC 8 with lower IC50 values
      than SAHA and Entinostat. Docking study with selected compounds 10f and 11a
      revealed that the compounds might bind tightly to the binding pockets in HDAC 2
      and HDAC 8, respectively. The results suggest that they may be promising lead
      compounds for the development of novel anti-tumor drug potentially via inhibiting
      HDACs.

PMID- 25874327
TI  - Exploring the chemical space of ureidothiophene-2-carboxylic acids as inhibitors
      of the quorum sensing enzyme PqsD from Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa employs a quorum sensing (QS) communication system that
      makes use of small diffusible molecules. Among other effects, the QS system
      coordinates the formation of biofilm which decisively contributes to difficulties
      in the therapy of Pseudomonas infections. The present work deals with the
      structure-activity exploration of ureidothiophene-2-carboxylic acids as
      inhibitors of PqsD, a key enzyme in the biosynthetic pathway of signal molecules
      in the Pseudomonas QS system. We describe an improvement of the inhibitory
      activity by successfully combining features from two different PqsD inhibitor
      classes. Furthermore the functional groups, which are responsible for the
      inhibitory potency, were identified. Moreover, the inability of the new
      inhibitors, to prevent signal molecule formation in whole cell assays, is
      discussed. 

PMID- 25874328
TI  - Design and synthesis of 3-(3-((9H-carbazol-4-yl)oxy)-2-hydroxypropyl)-2
      phenylquinazolin-4(3H)-one derivatives to induce ACE inhibitory activity.
AB  - In an attempt to develop a new class of cardiovascular drugs, a series of novel
      carbazolyloxy phenylquinazoline derivatives 9a-g have been synthesized and
      evaluated as angiotensin converting enzyme (ACE) inhibitors. Most of these
      compounds exhibited activity as significant ACE inhibitors and three compounds
      (9b, 9c & 9e) showed maximum inhibitory potency in enzyme based assays. To render
      support to the experimental results, a series of quinazolinone derivatives were
      docked into active site of ACE and identified the probable binding modes compared
      to Lisinopril. Also we have identified common pharmacophore hypothesis (AAADDRR)
      among the best docked conformers of most potent compounds in a series of
      compounds. The most potent 9b, 9c, 9e compounds shared common active site with
      the Lisinopril binding site and retained the key active site residue
      interactions. The obtained results from pharmacological and molecular modeling
      studies can be utilized for further optimization of identified hits for selective
      inhibition of ACE.

PMID- 25874329
TI  - Development of selective DprE1 inhibitors: Design, synthesis, crystal structure
      and antitubercular activity of benzothiazolylpyrimidine-5-carboxamides.
AB  - Decaprenylphosphoryl-b-D-ribose 20-epimerase (DprE1) is a potential drug target
      for development of antitubercular agents. Structure based drug discovery approach
      yielded twenty novel derivatives of benzothiazolylpyrimidine-5-carboxamides (7a
      t) which were synthesised by three component one pot reaction involving
      benzothiazolyl oxobutanamide, thiourea and substituted aromatic benzaldehydes.
      These derivatives were evaluated for antitubercular activity to determine MIC and
      compound 7a, 7e, 7f and 7o were found to be potentially active against
      Mycobacterium tuberculosis (H37Rv). Log P of these compounds was found to be
      between 2.0 and 3.0 making them suitable for oral dosing. DprE1 selectivity and
      pharmacokinetic studies were carried out for these compounds of which 7a and 7o
      were found to be highly selective and bioavailability was found to be above 52%
      by oral dose. Crystal structure of 7a was studied and molecular packing was
      determined, it exhibited a triclinic crystal lattice arrangement having hydrogen
      bonded dimeric arrangement. Drug receptor interactions were studied which
      exhibited docking in the active site of receptor with hydrogen bonding,
      hydrophobic interactions, vdW interactions with amino acid residues such as
      Cys387, Asn385, Lys418, Tyr314, Gln334 and Lys367 respectively. 3D QSAR analysis
      was carried out by kNN-MFA method to determine and develop theoretical model,
      best suitable model was found to be based on Simulated Annealing k-Neariest
      Neighbour Molecular Field Analysis (SA kNN-MFA). The model provided with
      hydrophobic descriptors in positive side indicating the need of bulky groups,
      steric and electronegative descriptors in negative coordinates hints with
      contribution by the electronegative substitutions as favourable and desirable
      moieties for enhancing the activity. The q(2), q(2)_se and Pred_r(2)se were found
      to be 0.5000, 0.6404 and 1.0094 respectively. A pharmacophore model was generated
      which suggested for necessity of aromatic, aliphatic carbon centre and hydrogen
      bond donor for development of newer DprE1 selective inhibitors.

PMID- 25874330
TI  - Regioselective chemical and rapid enzymatic synthesis of a novel redox -
      Antiproliferative molecular hybrid.
AB  - Recent science evidenced the interlinkage of oxidative stress and cancer. Due to
      the inherent complexity of cancer and its accompanying effect of oxidative
      stress, novel molecules, containing combinatorial functionalities should be
      targeted. Herein, we synthesized gemcitabine-5'-O-lipoate derived from a
      regioselective coupling of the chemotherapeutic drug gemcitabine (GEM), a first
      line agent for cancer therapy and alpha-lipoic acid (LA), a potent antioxidant.
      gemcitabine-5'-O-lipoate was obtained in 4 chemical steps. To avoid the tedious
      and laborious chemical steps we also utilized biocatalysis using immobilized
      Candida antarctica lipase B (CALB), and the optimum conditions for the
      regioselective and one-pot synthesis of gemcitabine-5'-O-lipoate were established
      by exploiting different solvents (organic solvents and ionic liquids) and enzyme
      immobilization (acrylic resin and carbon nanotubes). Cytotoxic activity of co
      administrating GEM and LA was proven to be synergistic against non-small cell
      lung cancer cells whereas antagonistic for bladder cancer cells. In contrast, the
      gemcitabine-5'-O-lipoate hybrid was found to be superior to the parent compounds
      against both non-small cell lung cancer and bladder cancer cells as also was
      found to preserve the redox activity of the parent compound LA. The
      regioselective biotransformation mediated synthesis of the anticancer-antioxidant
      hybrid illustrates the capacity of biocatalysis to act as an asset in molecular
      hybridization techniques.

PMID- 25874331
TI  - Synthesis and biological evaluation of betulonic acid derivatives as antitumor
      agents.
AB  - Structural modification was performed at the C-28 position of betulonic acid
      (BetA). Twenty-five BetA derivatives were synthesized, and evaluated for their
      antitumor activities against MGC-803, PC3, Bcap-37, A375, and MCF-7 human cancer
      cell lines by MTT assay. Among the derivatives, most of the derivatives had
      significant antiproliferative ability (IC50 < 19 MUM). Compound 3k, the most
      active compound, showed IC50 values of 3.6, 5.6, 4.2, 7.8, and 5.2 MUM on the
      five cancer cell lines respectively, and was selected to investigate cell
      apoptosis by subsequent florescence staining and flow cytometry analysis. The
      results revealed that compound 3k could induce apoptosis in MGC-803 cell lines,
      and the apoptosis ratios reached 28.33% after 36 h of treatment at 10 MUM. In
      addition, the study of cancer cell apoptotic signaling pathway indicated that the
      apoptosis of MGC-803 cells induced by compound 3k could be through the
      mitochondrial intrinsic pathway.

PMID- 25874332
TI  - A mononuclear Cu(II) complex with 5,6-diphenyl-3-(2-pyridyl)-1,2,4-triazine:
      Synthesis, crystal structure, DNA- and BSA-binding, molecular modeling, and
      anticancer activity against MCF-7, A-549, and HT-29 cell lines.
AB  - The copper(II) complex of 1,2,4-triazine derivatives, [Cu(dppt)2(H2O)](PF6)2(dppt
      is 5,6-diphenyl-3-(2-pyridyl)-1,2,4-triazine), has been synthesized and fully
      characterized by spectroscopic methods and single crystal X-ray diffraction. The
      in vitro DNA-binding studies of the complex have been investigated by several
      methods. The results showed that the complex intercalates into the base pairs of
      DNA. The complex also indicated good binding propensity to BSA. The results of
      molecular docking and molecular dynamic simulation methods confirm the
      experimental results. Finally, the in vitro cytotoxicity indicate that the
      complex has excellent anticancer activity against the three human carcinoma cell
      lines, MCF-7, A-549, and HT-29, with IC50 values of 9.8, 7.80, and 4.50 MUM,
      respectively. The microscopic analyses of the cancer cells demonstrate that the
      Cu(II) complex apparently induced apoptosis.

PMID- 25874333
TI  - Novel naftopidil-related derivatives and their biological effects as alpha1
      adrenoceptors antagonists and antiproliferative agents.
AB  - Eleven novel naftopidil-related compounds that contain amide and indole groups
      were designed and synthesized. The biological effects of these compounds on three
      alpha1-adrenoceptor subtypes and cancerous human prostate cell lines (PC-3, DU
      145, and LNCaP) were determined. Compounds 2, 3, 5, 11, and 12 exhibited an
      alpha1-adrenoceptor antagonistic activity, whereas compounds 9, 10, and 12
      displayed moderate antiproliferative activities. Compound 3 exhibited a
      significant alpha(1D/1A) blocking activity in isolated rat tissues (97.7- and
      64.6-fold selective for alpha(1D) and alpha(1A) compared with alpha(1B)) but not
      a relevant cytotoxic activity. Compound 12 demonstrated a potent and selective
      alpha(1D/1A) antagonistic activity (47.9- and 19.1-fold for alpha(1D) and
      alpha(1A) compared with alpha1B) and a potent antiproliferative activity in PC-3
      cells (IC50 = 15.70 MUM). Further testing confirmed that compound 12 inhibited
      the growth of PC-3 cells by inducing apoptosis and G0/G1 cell cycle arrest, which
      was mediated by alpha1-adrenoceptor. Therefore, compound 12 is a potential
      multipotent agent that can act as an effective alpha1-adrenoceptor subtype
      antagonist for treating benign prostatic hyperplasia and a preventive medication
      against human prostate cancer.

PMID- 25874334
TI  - Synthesis of selenazolopyridine derivatives with capability to induce apoptosis
      in human breast carcinoma MCF-7 cells through scavenge of intracellular ROS.
AB  - A series of selenazolopyridine derivatives have been synthesized and
      characterized by X-ray diffraction, high resolution NMR and Mass spectrum. The in
      vitro anticancer activities of the synthetic compounds were screened against a
      panel of human cancer cell lines, human breast carcinoma MCF-7 cells, human liver
      carcinoma HepG2 cells and L02 normal cell line by MTT assay. By analyzing the
      structure-activity relationship among the synthetic compounds, it was found that
      2-(phenylamino) selenazolo [5,4-b] pyridine, (PSeD, 7) had higher growth
      inhibitory effect on MCF-7 cells. The intracellular mechanism of cell death was
      evaluated by flow cytometric analysis and ROS assay, which revealed that PSeD
      could induce MCF-7 cells apoptosis by scavenging intracellular ROS. Taken
      together, we regard PSeD as an antioxidant which could inhibit cancer cell growth
      through induction of apoptosis.

PMID- 25874335
TI  - Synthesis and antiproliferative activity of 3-(2-chloroethyl)-5-methyl-6-phenyl-8
      (trifluoromethyl)-5,6-dihydropyrazolo[3,4-f][1,2,3,5]tetrazepin-4-(3H)-one.
AB  - Based on the encouraging results found for 3,5-dimethyl-6-phenyl-8
      (trifluoromethyl)-5,6-dihydropyrazolo[3,4-f][1,2,3,5]tetrazepin-4-(3H)-one 7
      previously tested by us, as well as the consideration that heterocycle fused
      tetrazepinones bearing the 2-chloroethyl substituent show a better cytotoxic
      profile than temozolomide and mitozolomide against human cancer cell lines which
      express the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT), in
      this paper we report the multistep synthesis and the biological study of 3-(2
      chloroethyl)-5-methyl-6-phenyl-8-(trifluoromethyl)-5,6-dihydropyrazolo[3,4
      f][1,2,3,5]tetrazepin-4-(3H)-one 10. Like compound 7, it was active on P
      glycoprotein expressing cells (MDR) HL60 and on K562 cell line that are resistant
      to apoptosis induced by different stimuli, showing GI50 values of 14 and 18 MUM
      respectively. As an antiproliferative agent against the above cells compound 10
      was about 2.2 times more active than compound 7. Compound 10 was also tested
      against WiDR cells which are overexpressing the DNA repair protein MGMT, showing
      a GI50 value of 2.3 MUM. Finally, concerning the effect on cell cycle we observed
      an evident difference between compounds 7 and 10. In fact, compound 7 induces a
      block of cell cycle in G0-G1, therefore acting as phase-specific drug, in
      contrast, compound 10 is a not phase-specific agent. Both the compounds are able
      to increase the apoptotic sub G0-G1 peak of cell cycle.

PMID- 25874336
TI  - Exploring the 7-oxo-thiazolo[5,4-d]pyrimidine core for the design of new human
      adenosine A3 receptor antagonists. Synthesis, molecular modeling studies and
      pharmacological evaluation.
AB  - A new series of 5-methyl-thiazolo[5,4-d]pyrimidine-7-ones bearing different
      substituents at position 2 (aryl, heteroaryl and arylamino groups) was
      synthesized and evaluated in radioligand binding assays to determine their
      affinities at the human (h) A1, A2A, and A3 adenosine receptors (ARs). Efficacy
      at the hA(2B) and antagonism of selected ligands at the hA3 were also assessed
      through cAMP experiments. Some of the new derivatives exhibited good to high
      hA3AR affinity and selectivity versus all the other AR subtypes. Compound 2-(4
      chlorophenyl)-5-methyl-thiazolo[5,4-d]pyrimidine-7-one 4 was found to be the most
      potent and selective ligand of the series (K(I) hA3 = 18 nM). Molecular docking
      studies of the reported derivatives were carried out to depict their hypothetical
      binding mode in our hA3 receptor model.

PMID- 25874337
TI  - Design, synthesis and structural exploration of novel fluorinated dabigatran
      derivatives as direct thrombin inhibitors.
AB  - Twenty-one fluorinated dabigatran derivatives were designed based on the
      bioisosteric principle. All derivatives were synthesised and evaluated for their
      thrombin inhibitory activity in vitro. Among these compounds, 14h, 14m, 14s and
      14t were potent and the activity was in the range of reference drug, dabigatran.
      Three structural changes were introduced in these 21 compounds to elucidate the
      structure-activity relationship of the drugs. In addition, prodrugs of compounds
      14h and 14s were developed to investigate their anticoagulant activities in vivo.
      In these experiments, compound 16 showed a fairly strong inhibitory effect on
      thrombin-induced platelet aggregation, and demonstrated potent activity for
      inhibiting arteriovenous thrombosis with an inhibition rate of (73 +/- 6) %,
      which was comparable to that of dabigatran etexilate (76 +/- 2) %. Moreover,
      molecular docking studies were performed to understand the binding interactions
      of active compounds 14h, 14s and 14t with thrombin protein (PDB ID:1KTS). Contour
      maps obtained from the 3D-QSAR model are meaningful in designing more active
      molecules to act as direct inhibitors of thrombin.

PMID- 25874338
TI  - Identification of 4-(4-nitro-2-phenethoxyphenyl)pyridine as a promising new lead
      for discovering inhibitors of both human and rat 11beta-Hydroxylase.
AB  - The inhibition of 11beta-hydroxylase is a promising strategy for the treatment of
      Cushing's syndrome, in particular for the recurrent and subclinical cases. To
      achieve proof of concept in rats, efforts were paid to identify novel lead
      compounds inhibiting both human and rat CYP11B1. Modifications on a potent
      promiscuous inhibitor of hCYP11B1, hCYP11B2 and hCYP19 (compound IV) that
      exhibited moderate rCYP11B1 inhibition led to compound 8 as a new promising lead
      compound. Significant improvements compared to starting point IV were achieved
      regarding inhibitory potency against both human and rat CYP11B1 (IC50 values of 2
      and 163 nM, respectively) as well as selectivity over hCYP19 (IC50 = 1900 nM).
      Accordingly, compound 8 was around 7- and 28-fold more potent than metyrapone
      regarding the inhibition of human and rat CYP11B1 and exhibited a comparable
      selectivity over hCYP11B2 (SF of 3.5 vs 4.9). With further optimizations on this
      new lead compound 8, drug candidates with satisfying profiles are expected to be
      discovered.

PMID- 25874339
TI  - Synthesis of a novel class of substituted benzothiophene or benzofuran
      derivatives as BMP-2 up-regulators and evaluation of the BMP-2-up-regulating
      effects in vitro and the effects on glucocorticoid-induced osteoporosis in rats.
AB  - The BMP pathway is a promising new target for the design of therapeutic agents
      for the treatment of low bone mass. To enrich our understanding of SAR and based
      on our previously concluded structure-effect relationship, 23 derivatives were
      prepared in this work. The synthesis, up-regulating activities on BMP-2
      expression, and bone loss prevention efficacies of these compounds in rats with
      glucocorticoid-induced osteoporosis are presented. The bone histology of the
      tested rats assessed through light microscopy showed that compounds 1, 21, 35,
      and 38 significantly increased the trabecula compared with the model group, and
      the trabecula of the groups treated with 8a was similar to that obtained with
      raloxifene and alfacalcidol. The compounds exhibited potential for development as
      anabolic agents. 

PMID- 25874341
TI  - Design, synthesis, biological evaluation and preliminary mechanism study of novel
      benzothiazole derivatives bearing indole-based moiety as potent antitumor agents.
AB  - Through a structure-based molecular hybridization approach, a series of novel
      benzothiazole derivatives bearing indole-based moiety were designed, synthesized
      and screened for in vitro antitumor activity against four cancer cell lines
      (HT29, H460, A549 and MDA-MB-231). Most of them showed moderate to excellent
      activity against all the tested cell lines. Among them, compounds 20a-w with
      substituted benzyl-1H-indole moiety showed better selectivity against HT29 cancer
      cell line than other compounds. Compound 20d exhibited excellent antitumor
      activity with IC50 values of 0.024, 0.29, 0.84 and 0.88 MUM against HT29, H460,
      A549 and MDA-MB-231, respectively. Further mechanism studies indicated that the
      marked pharmacological activity of compound 20d might be ascribed to activation
      of procaspase-3 (apoptosis-inducing) and cell cycle arrest, which had emerged as
      a lead for further structural modifications. Furthermore, 3D-QSAR model (training
      set: q(2) = 0.850, r(2) = 0.987, test set: r(2) = 0.811) was built to provide a
      comprehensive guide for further structural modification and optimization.

PMID- 25874340
TI  - Novel imidazole derivatives as heme oxygenase-1 (HO-1) and heme oxygenase-2 (HO
      2) inhibitors and their cytotoxic activity in human-derived cancer cell lines.
AB  - Heme oxygenase (HO) is a cytoprotective enzyme that can be overexpressed in some
      pathological conditions, including certain cancers. In this work, novel imidazole
      derivatives were designed and synthesized as inhibitors of heme oxygenase-1 (HO
      1) and heme oxygenase-2 (HO-2). In these compounds the imidazole ring, crucial
      for the activity, is connected to a hydrophobic group, represented by aryloxy,
      benzothiazole, or benzoxazole moieties, by means of alkyl or thioalkyl chains of
      different length. Many of the tested compounds were potent and/or selective
      against one of the two isoforms of HO. Furthermore, most of the pentyl
      derivatives showed to be better inhibitors of HO-2 with respect to HO-1,
      revealing a critical role of the alkyl chain in discriminating between the two
      isoenzymes. Compounds which showed the better profile of HO inhibition were
      selected and tested to evaluate their cytotoxic properties in prostate and breast
      cancer cell lines (DU-145, PC3, LnCap, MDA-MB-231, and MCF-7). In these assays,
      aryloxyalkyl derivatives resulted more cytotoxic than benzothiazolethioalkyl
      ones; in particular compound 31 was active against all the cell lines tested,
      confirming the anti-proliferative properties of HO inhibitors and their potential
      use in the treatment of specific cancers.

PMID- 25874342
TI  - Cytotoxicity profile of novel sterically hindered platinum(II) complexes with
      (1R,2R)-N(1),N(2)-dibutyl-1,2-diaminocyclohexane.
AB  - Four Pt(II) complexes of (1R,2R)-N(1),N(2)-dibutyl-1,2-diaminocyclohexane with
      two alkyl branches as steric hindrance have been designed and synthesized. In
      vitro cytotoxicity of these compounds indicated complex 4 is a cytotoxic agent
      more potent than its parent molecule, oxaliplatin, against almost all the tested
      cell lines. Agarose gel electrophoresis study showed that the kinetic reactivity
      of complex 4 with DNA is slow down due to the sterically hindered effect,
      demonstrating that it may possess a different mechanism of action from cisplatin.
      Flow cytometry results revealed that complex 4 induced apoptosis of tumor cells
      by blocking the cell-cycle progression in the G2/M phase. Western blot analysis
      showed it had a similar apoptotic mechanism to cisplatin which could induce
      apoptosis via a mitochondrial-dependent pathway.

PMID- 25874343
TI  - Synthesis, molecular modeling, and biological evaluation of novel RAD51
      inhibitors.
AB  - RAD51 recombinase plays a critical role for cancer cell proliferation and
      survival. Targeting RAD51 is therefore an attractive strategy for treating
      difficult-to-treat cancers, e.g. triple negative breast cancers which are often
      resistant to existing therapeutics. To this end, we have designed, synthesized
      and evaluated a panel of new RAD51 inhibitors, denoted IBR compounds. Among these
      compounds, we have identified a novel small molecule RAD51 inhibitor, IBR120,
      which exhibited a 4.8-fold improved growth inhibition activity in triple negative
      human breast cancer cell line MBA-MD-468. IBR120 also inhibited the proliferation
      of a broad spectrum of other cancer cell types. Approximately 10-fold difference
      between the IC50 values in normal and cancer cells were observed. Moreover,
      IBR120 was capable of disrupting RAD51 multimerization, impairing homologous
      recombination repair, and inducing apoptotic cell death. Therefore, these novel
      RAD51 inhibitors may serve as potential candidates for the development of
      pharmaceutical strategies against difficult-to-treat cancers. 

PMID- 25874344
TI  - Progress testing in undergraduate dental education: the Peninsula experience and
      future opportunities.
AB  - BACKGROUND: Progress testing is well established as a longitudinal form of
      assessment in undergraduate medical programmes to measure growth in knowledge.
      Peninsula Dental School is the first school to use progress testing and remains
      the only one to do so. AIMS: To share the experience of developing progress
      testing in an undergraduate dental programme as a major summative assessment tool
      at a newly established dental school in the United Kingdom. METHODS: Data were
      collected for progress tests conducted from 2007 to 14. The tests were formative
      in the first 2 years of the programme and summative in subsequent years. Each
      test was based on 100 single best answer multiple-choice items with an
      appropriate vignette. The students chose their answer from 5 options. A score 1
      mark is awarded for each correct answer, minus 0.25 for an incorrect answer and 0
      for 'don't know' (DK). The standard setting for each sitting was carried out
      using Angoff and Hofstee methods. RESULTS: There were two tests per year with
      each cohort undertaking eight tests in their 4 years of study providing a total
      14 test occasions. The reliability of each test for each student cohort tests was
      measured using Cronbach's alpha. The average reliability over 42 test/cohort
      combinations was 0.753 (+/-SD 0.08). Data analyses show growth in knowledge of
      dental students across successive years with the largest increase in knowledge
      observed between tests 1 and 5 and concomitant reduction in DK responses.
      CONCLUSION: This is the first study to report the establishment and use of
      progress testing as the principle form of written summative testing in an
      undergraduate dental curriculum. Progress testing is a valid and reliable tool to
      assess growth in knowledge longitudinally over the duration of a dental
      programme. Although a labour-intensive process, progress testing merits more
      widespread use in dental programmes.

PMID- 25874345
TI  - New ACR EULAR guidelines for systemic sclerosis classification.
AB  - The American College of Rheumatology and European League Against Rheumatism
      classification criteria for systemic sclerosis are a significant advancement in
      the field. This article describes the innovative, rigorous, criteria development
      strategy that was used. The new criteria build upon previous criteria by
      incorporating important elements (proximal scleroderma, sclerodactyly, digital
      pits, pulmonary fibrosis, Raynaud's phenomenon, and scleroderma specific
      autoantibodies). The new criteria add emphasis to the vasculopathic
      manifestations, and include the early manifestation of puffy fingers. Together,
      these enhancements have resulted in a shift in the conceptual framework of the
      disease for the next generation. The new criteria have improved sensitivity and
      specifically, particularly among cases with early disease, mild disease, or
      limited disease. The ability to classify more cases, at an earlier stage, may
      confer the opportunity to intervene and prevent disease progression. Undoubtedly,
      this will lead to a paradigm shift in the conduct of clinical trials in systemic
      sclerosis. 

PMID- 25874346
TI  - IL-23 responsive innate-like T cells in spondyloarthritis: the less frequent they
      are, the more vital they appear.
AB  - A key role for the IL-23/IL-17 immune axis in spondyloarthritis (SpA) is
      supported by cumulative evidence from genetic and translational studies and was
      recently confirmed in clinical trials. Although initially linked to T helper 17
      cells, it is now clear that additional unconventional T cell subpopulations
      respond towards IL-23, including RORgammat(+) CD3(+)CD4(-)CD8(-) T cells,
      TCRgammadelta17 cells, KIR3DL2(+)CD4(+) T cells and iNKT17 cells. Although these
      innate-like T cells are present only at low frequencies and often with a specific
      tissue distribution, it is proposed that they could play a vital function in the
      development or progression of SpA-related pathology. In this review, we highlight
      the emerging knowledge on these specialized IL-23 responsive T cells with regard
      to their relevance in SpA. Finally, we will discuss these findings in light of
      novel drugs targeting the IL-23/IL-17 axis, currently being tested in SpA
      patients. 

PMID- 25874347
TI  - The humanistic and economic burden of juvenile idiopathic arthritis in the era of
      biologic medication.
AB  - Juvenile idiopathic arthritis (JIA) is a poorly understood, heterogeneous,
      incurable, inflammatory syndrome. Long-term outcomes are uncertain, and this
      painful condition can result in lifelong disability. JIA is associated with
      considerable financial and humanistic burden for those affected and the
      healthcare system. Early diagnosis and effective treatment are indicated to
      optimise outcomes. Modern treatment aims to achieve remission and preserve joint
      function by using disease-modifying antirheumatic drugs (DMARDs) early. DMARDs
      can be classified as conventional/traditional or biologic. Biologic medications
      may be more effective but cost approximately ten times more than traditional
      DMARDs. Decision-makers in healthcare are increasingly comparing the cost and
      consequences of alternative treatment strategies to guide resource allocation
      decisions. There have been few economic evaluations to date to guide medicines
      optimisation in JIA. This systematic review highlights the lack of existing
      evidence relating to the humanistic and economic burden of JIA in the era of
      biologic medication. 

PMID- 25874349
TI  - NPR1-dependent salicylic acid signaling is not involved in elevated CO2-induced
      heat stress tolerance in Arabidopsis thaliana.
AB  - Elevated CO2 can protect plants from heat stress (HS); however, the underlying
      mechanisms are largely unknown. Here, we used a set of Arabidopsis mutants such
      as salicylic acid (SA) signaling mutants nonexpressor of pathogenesis-related
      gene 1 (npr1-1 and npr1-5) and heat-shock proteins (HSPs) mutants (hsp21 and
      hsp70-1) to understand the requirement of SA signaling and HSPs in elevated CO2
      induced HS tolerance. Under ambient CO2 (380 umol mol(-1)) conditions, HS (42
      degrees C, 24 h) drastically decreased maximum photochemical efficiency of PSII
      (Fv/Fm) in all studied plant groups. Enrichment of CO2 (800 umol mol(-1)) with HS
      remarkably increased the Fv/Fm value in all plant groups except hsp70-1,
      indicating that NPR1-dependent SA signaling is not involved in the elevated CO2
      induced HS tolerance. These results also suggest an essentiality of HSP70-1, but
      not HSP21 in elevated CO2-induced HS mitigation. 

PMID- 25874348
TI  - Cystine growth inhibition through molecular mimicry: a new paradigm for the
      prevention of crystal diseases.
AB  - Cystinuria is a genetic disease marked by recurrent kidney stone formation,
      usually at a young age. It frequently leads to chronic kidney disease. Treatment
      options for cystinuria have been limited despite comprehensive understanding of
      its genetic pathophysiology. Currently available therapies suffer from either
      poor clinical adherence to the regimen or potentially serious adverse effects.
      Recently, we employed atomic force miscopy (AFM) to identify L-cystine
      dimethylester (CDME) as an effective molecular imposter of L-cystine, capable of
      inhibiting crystal growth in vitro. More recently, we demonstrated CDME's
      efficacy in inhibiting L-cystine crystal growth in vivo utilizing a murine model
      of cystinuria. The application of AFM to discover inhibitors of crystal growth
      through structural mimicry suggests a novel approach to preventing and treating
      crystal diseases. 

PMID- 25874350
TI  - Anhedonia in depressed patients on treatment with selective serotonin reuptake
      inhibitor anti-depressant--A two-centered study in Malaysia.
AB  - OBJECTIVE: Anhedonia is the reduced ability to experience pleasure. It is a core
      symptom of depression and is particularly difficult to treat. This study aims to
      compare the level of anhedonia between depressed patients on anti-depressants and
      healthy subjects. METHOD: A total of 111 depressed patients on selective
      serotonin reuptake inhibitor (SSRI) and 82 healthy subjects were recruited from
      the outpatient psychiatric services at two major general hospitals in a cross
      sectional study. Subjects were assessed using the Mini International
      Neuropsychiatric Interview 5.0.0 or MINI, Beck's Depression Index (BDI), and
      Snaith-Hamilton Pleasure Scale (SHAPS). Relevant personal and sociodemographic
      information were also collected. RESULTS: There was a significant association
      between educational level and SHAPS-M scores (P < 0.01) among the participants.
      Most items in the SHAPS scores were significantly different (P < 0.01) in the
      depressed subjects treated with anti-depressant compared with the healthy
      subjects, after adjusting the confounding factors, BDI score, and educational
      level. CONCLUSION: Anhedonia often persists in depressed patients despite on SSRI
      anti-depressant treatment.

PMID- 25874351
TI  - Strontium and osteoblast function.

PMID- 25874352
TI  - Strontium: friend or foe of bone formation?

PMID- 25874353
TI  - Use of artificial dermal substitute as a bridge in complex finger reconstruction.
AB  - Few reports exist regarding the use of an artificial dermal substitute ([ADS]
      IntegraTM) in the treatment of finger injuries. This retrospective case series
      evaluated the use of ADS as a bridge for finger reconstruction following complex
      injuries. The authors' facility treated 26 complex finger injury patients using
      ADS. Graft take was 92.3% (22/26), with most patients experiencing satisfactory
      range of motion (88.5% or 23/26). The authors conclude that ADS, as a bridge for
      reconstruction of complex finger injuries, offers advantages, such as improved
      contour, functionality, and decreased need for native flaps. 

PMID- 25874354
TI  - Sleep Quality Among Patients With Venous Ulcers: A Cross-sectional Study in a
      Health Care Setting in Sao Paulo, Brazil.
AB  - This was an exploratory, descriptive, cross-sectional study to assess sleep
      quality in 100 patients with venous ulcers using the Pittsburgh Sleep Quality
      Index (PSQI). Thirty-six (36%) patients had a global PSQI score < 5, indicating
      that they were good sleepers, while 64 (64%) patients were considered poor
      sleepers. Fifty-three (53%) patients reported going to bed between 9:00 pm and
      11:00 pm, 63 (63%) taking from 16 to 30 minutes to fall asleep, and 41 (41%)
      waking up after 4 to 5 hours of sleep. Sixty (60%) patients regarded sleeping as
      a necessity. Most patients with venous ulcers experienced poor sleep quality.   
      . 

PMID- 25874355
TI  - The effect of a hydroconductive dressing on the suppression of wound biofilm.
AB  - Although excessive exudate has been associated with poor wound healing outcomes,
      exudate is still not well understood in the pathophysiology of chronic wounds.
      Wound exudate is believed to be the result of wounds that are trapped in a
      persistent, hyper inflammatory state. Biofilm, bacteria of multiple species
      living in community, has multiple well-defined molecular pathways that produce
      hyper inflammation. The exudate that is produced in wounds is a potentially
      important nutrient source for biofilm; therefore, rapidly removing exudate may
      rob the biofilm of important nutrients and suppress its negative effects.
      METHODS: A hydroconductive fiber dressing that possesses excellent capillary
      action properties was utilized to rapidly remove wound exudate in 10 patients.
      RESULTS: The data demonstrate an average 62% reduction in wound volume for these
      10 wounds over a 4-week period. Two wounds completely closed during the 2 weeks,
      and all but 1 wound significantly improved. Only 6 of the 10 wounds showed fewer
      bacteria at the end of the 4-week study period, suggesting there is not a 1:1
      correlation with reduction in the number of bacteria in the wound and wound
      healing. CONCLUSION: Rapid removal of the nutrient source from wound biofilm,
      while not diminishing the number of bacteria, may suppress a biofilm's negative
      effects on wound healing.  .

PMID- 25874356
TI  - Physical therapy in the treatment of venous leg ulcers: biophysical mechanisms.
AB  - The present study sought to estimate the hemodynamic effects inside wounds after
      applying infrared thermography. Clinical results were analyzed to evaluate any
      correspondence with hemodynamic events occurring inside the wounds. METHODS:
      Group 1 consisted of 20 patients with venous leg ulcers (12 women, 8 men).
      Patients from group 1 received 1 high-voltage stimulation (HVS) procedure. Group
      2 consisted of 23 patients (16 women, 7 men). Patients from group 2 received 1
      ultrasound (US) procedure. Group 3 consisted of 21 patients (13 women, 8 men).
      Patients from group 3 received 1 low-level laser therapy (LLLT) procedure. Group
      4 consisted of 23 patients (15 women, 8 men). Patients from group 4 received 1
      compression therapy (CT) procedure. Group 5 consisted of 19 patients (11 women, 8
      men). Patients from group 5 received 1 quasi-CT procedure. Infrared thermography
      was used to monitor arterial hemodynamic effects for each ulcer. Infrared
      thermography, based on analysis of wound surface temperatures, was used to
      reflect normal or abnormal arterial circulation in capillaries. The average and
      maximal temperatures before and after each physical procedure were measured 5,
      10, 15, and 30 minutes afterward. RESULTS: The application of HVS and LLLT did
      not change the temperature inside the wounds. A significant temperature increase
      was noted after application of US and CT. The quasi-CT induced a thermal effect
      (only for a few minutes), but was not as intense as the effect of the compression
      stockings. The measurements showed a prolonged and steady thermal effect.
      CONCLUSION: The hemodynamic effect (improvement of arterial microcirculation
      inside the venous leg ulcer) is one of the most significant biophysical
      mechanisms of healing after clinically efficient compression therapy. Hemodynamic
      reactions are not basic mechanisms of high voltage stimulation and ultrasound
      therapy during the healing of venous leg ulcers. Computed thermography is a
      simple and useful tool to measure hemodynamic effects in wound healing.    .

PMID- 25874357
TI  - Involvement of reactive persulfides in biological bismethylmercury sulfide
      formation.
AB  - Bismethylmercury sulfide (MeHg)2S has been found to be a detoxified metabolite of
      methylmercury (MeHg) that is produced by SH-SY5Y cells and in livers of rats
      exposed to MeHg. (MeHg)2S could be formed through the interactions between MeHg
      and sulfur species such as hydrogen sulfide (H2S or HS(-)), but the origin of its
      sulfur has not been fully identified. We herein examined the formation of
      (MeHg)2S through interactions between MeHg and persulfides, polysulfides, and
      protein preparations. Investigations using HPLC/atomic absorption
      spectrophotometry and EI-MS revealed that NaHS and Na2S4 react readily with MeHg
      to give (MeHg)2S, and similar results were found using GSH persulfide (GSSH)
      formed endogenously or generated enzymatically in vitro. (MeHg)2S was also formed
      by incubation of MeHg with liver and heart cytosolic fractions prepared from wild
      type mice but not with those from mice lacking cystathionine gamma-lyase (CSE)
      that catalyzes the formation of cysteine persulfide. Consistent with this,
      (MeHg)2S was detected in a variety of tissues taken from wild-type mice
      intraperitoneally injected with MeHg in vivo but not in those from MeHg-injected
      CSE knockout mice. By separating liver fractions by column chromatography, we
      found numerous proteins that contain persulfides: one of the proteins was
      identified as being glutathione S-transferase pi 1. These results indicate that
      the formation of (MeHg)2S can be attributed to interactions between MeHg and
      endogenous free persulfide species, as well as protein-bound cysteine persulfide.

PMID- 25874358
TI  - Dysbiosis of gut microbiota induced the disorder of helper T cells in influenza
      virus-infected mice.
AB  - It is widely understood that commensal microbiota contributes to the maintenance
      of intestinal homeostasis through dynamic interactions with a body's immunity.
      And the immune regulation is important for the influenza vaccine's effectiveness
      after body injection, however, the mechanism between commensal microbiota and
      vaccine's effectiveness remains unknown. The impact that individual bacteria
      species have on the balance of the systemic immune system beyond the local
      intestinal mucosal tissues also remains less clear, and the related mechanism is
      still unknown. In this study, through the administration of various antibiotics,
      we examined the balance of helper T cell subsets in mice after inoculating them
      with the influenza virus and then, attempted to imitate the clinical practice in
      which patients are always prescribed with an antibiotic treatment in flu season.
      The data indicates that the mice in each group present differential immune
      responses in terms of the makeup of helper T cell subsets, although the Th17 cell
      activity seems to not be involved in the systemic immune modulation in the mice
      that are susceptible to the intervention of antibiotic. Th1, Th2, and anti
      inflammatory regulatory T cells have been implicated in the contribution to the
      systemic immune response influenced by the antibiotic-induced dysbiosis. Thus we
      believe that the normal intestinal flora could maintain the immune balance and
      inhibit the inflammatory responses, which may be useful for clinical application
      to take intestinal flora into consideration when influenza vaccination was used. 

PMID- 25874359
TI  - "Scientific proofs" and their interpretation.

PMID- 25874360
TI  - Excision of apocrine glands with preservation of axillary superficial fascia for
      the treatment of axillary bromhidrosis.
AB  - BACKGROUND: Axillary bromhidrosis is a distressing problem, which has a strong
      negative effect on one's social life. OBJECTIVE: To evaluate the effects and
      complications of the surgical modality for the treatment of axillary
      bromhidrosis. METHODS: One hundred fifteen patients with axillary bromhidrosis
      were treated. Two incisions were made transversely along the marked lines on the
      axillary crease. Subdermal undermining of the marked area with a depth of 0.3 to
      0.5 cm and transverse detachment were performed, allowing the exposure of the
      skin flaps. Skin flaps were carefully separated from the skin. The apocrine
      glands, follicles, and fats were dissected, and the axillary superficial fascia
      was maintained. RESULTS: All patients achieved good results in terms of malodor
      elimination during the follow-up period. All patients reported reduction in
      axillary sweating. Postoperative complications were minor, including small
      hematoma (3 cases), delayed wound healing (5 cases), pressure blister (5 cases),
      and slightly wound scar (2 cases). No infection, skin necrosis, malodor, or
      recurrence was observed. One hundred eleven patients (96.5%) were very satisfied
      and 4 (3.5%) patients satisfied with the procedure, with none regretful.
      CONCLUSION: The procedure has the advantage of a high success rate in radical
      elimination of the malodor with minor complications.

PMID- 25874361
TI  - An alar rim defect.

PMID- 25874363
TI  - Benzo[a]carbazole-Based Donor-pi-Acceptor Type Organic Dyes for Highly Efficient
      Dye-Sensitized Solar Cells.
AB  - A novel class of metal-free organic dyes based on benzo[a]carbazole have been
      designed, synthesized, and used in dye-sensitized solar cells for the first time.
      These types of dyes consisted of a cyanoacrylic acid moiety as the electron
      acceptor/anchoring group and different electron-rich spacers such as thiophene
      (JY21), furan (JY22), and oligothiophene (JY23) as the pi-linkers. The
      photophysical, electrochemical, and photovoltaic properties, as well as
      theoretical calculations of these dyes were investigated. The photovoltaic
      performances of these dyes were found to be highly relevant to the pi-conjugated
      linkers. In particular, dye JY23 exhibited a broad IPCE response with a
      photocurrent signal up to about 740 nm covering the most region of the UV-visible
      light. A DSSC based on JY23 showed the best photovoltaic performance with a Jsc
      of 14.8 mA cm(-2), a Voc of 744 mV, and a FF of 0.68, achieving a power
      conversion efficiency of 7.54% under standard AM 1.5 G irradiation. 

PMID- 25874364
TI  - Niche suitability affects development: skull asymmetry increases in less suitable
      areas.
AB  - For conservation purposes, it is important to take into account the suitability
      of a species to particular habitats; this information may predict the long-term
      survival of a species. In this sense, morphological measures of developmental
      stress, such as fluctuating asymmetry, can be proxies for an individual's
      performance in different regions. In this study, we conducted tests to determine
      whether areas with different levels of suitability for a species (generated by
      ecological niche models) were congruent with morphological markers that reflect
      environmental stress and morphological variance. We generated a Maxent niche
      model and compared the suitability assessments of several areas with the skull
      morphology data (fluctuating asymmetry and morphological disparity) of
      populations of the Atlantic forest endemic to Brazil rodent Akodon cursor. Our
      analyses showed a significant negative relationship between suitability levels
      and fluctuating asymmetry levels, which indicates that in less suitable areas,
      the individuals experience numerous disturbances during skull ontogeny. We have
      not found an association between morphological variance and environmental
      suitability. As expected, these results suggest that in environments with a lower
      suitability, developmental stress is increased. Such information is helpful in
      the understanding of the species evolution and in the selection of priority areas
      for the conservation of species. 

PMID- 25874365
TI  - Diagnostic and Therapeutic Challenges.

PMID- 25874366
TI  - ASSOCIATION OF PREVASCULAR VITREOUS FISSURES AND CISTERNS WITH VITREOUS
      DEGENERATION AS ASSESSED BY SWEPT SOURCE OPTICAL COHERENCE TOMOGRAPHY.
AB  - PURPOSE: To demonstrate the presence of prevascular vitreous fissures (PVF) and
      posterior vitreous cisterns in vivo and correlate with the degree of vitreous
      degeneration (VD). METHODS: This was a cross-sectional study using Topcon Deep
      Range Imaging OCT-1 Atlantis 3D swept source optical coherence tomography for
      acquiring scans of posterior vitreous covering an 18 * 18-mm area in 104 eyes of
      52 healthy volunteers without posterior vitreous detachment. RESULTS: We observed
      that increasing age was associated with higher VD grades (P < 0.05). Prevascular
      vitreous fissures, characterized by areas of lower optical density overlying the
      retinal blood vessels, were identified in 93 (89%) eyes, and the presence of PVF
      correlated with lower VD grades (P < 0.05). Presence of cisterns correlated with
      higher VD grades (P < 0.05). All eyes with absence of PVF were found to have
      established cisterns. Prevascular vitreous fissures were connected with cisterns
      in 44 of the 71 (62%) eyes with cisterns, while the base of the cistern was
      directly above retinal blood vessels in 38 (54%) eyes, which suggests that the
      cisterns could be derived from PVF. CONCLUSION: Swept source optical coherence
      tomography imaging can identify PVF and cisterns occurring in the context of age
      related VD, and PVF appeared to be possible precursors of cisterns.

PMID- 25874367
TI  - PARS PLANA VITRECTOMY FOR SYMPTOMATIC EPIRETINAL MEMBRANES IN EYES WITH 20/50 OR
      BETTER PREOPERATIVE VISUAL ACUITY.
AB  - PURPOSE: To evaluate pars plana vitrectomy with membrane peel for symptomatic
      epiretinal membranes in eyes with preoperative best-corrected visual acuity of
      20/50 or better. METHODS: Patients with symptomatic epiretinal membrane and 20/50
      or better vision who underwent pars plana vitrectomy with membrane peel by a
      single surgeon at our institution between January 2007 and January 2014 were
      identified. The principal outcomes measured were best-corrected visual acuity and
      central subfield macular thickness at 1, 6, and 12 months of follow-up.
      Subjective improvement in patient symptoms and complications were also
      documented. RESULTS: Thirty-three eyes of 33 consecutive patients were included
      in this retrospective case series. Mean preoperative best-corrected visual acuity
      was 20/40 and improved to 20/28 (P = 0.00008) at Month 12. Mean central subfield
      macular thickness improved from 437 MUm preoperatively to 391 MUm by Month 1 (P =
      0.00006) and 388 MUm at 12 months (P = 0.00142). Seventy-three percent (24 of 33)
      of patients (95% confidence interval: 55.6-85.1%) reported improvement of visual
      symptoms during the follow-up period. Of the 13 patients who were phakic
      preoperatively, 6 patients (46.1%, 95% confidence interval: 23.2-70.9%) underwent
      phacoemulsification surgery within 1 year of vitrectomy. CONCLUSION: Patients
      experienced a gradual gain in acuity and improvement of symptoms after pars plana
      vitrectomy with membrane peel. Cataract progression necessitating cataract
      surgery is common in phakic patients.

PMID- 25874368
TI  - PERIPAPILLARY CHOROIDAL THICKNESS IN CENTRAL SEROUS CHORIORETINOPATHY: Is Choroid
      Outside the Macula Also Thick?
AB  - PURPOSE: To investigate peripapillary choroidal thickness (CT) outside the macula
      in central serous chorioretinopathy (CSC). METHODS: We reviewed the medical
      records of 34 patients with unilaterally symptomatic idiopathic CSC and 34 age
      matched controls. Subfoveal and peripapillary CT were measured from images
      obtained by spectral domain optical coherence tomography. The nasal peripapillary
      CT of the choroid outside the macula was determined. RESULTS: The subfoveal CT of
      CSC (369.74 +/- 54.17 MUm) and fellow eyes (316.18 +/- 54.68 MUm) of the patient
      group were thicker than those of the normal controls (281.90 +/- 40.97 MUm, all P
      < 0.05). The subfoveal CT in CSC was significantly thicker than those in the
      fellow eyes. Nasal CT was also thicker in CSC (217.59 +/- 62.03 MUm) and fellow
      eyes (206.66 +/- 59.35 MUm) of the patient group compared with the normal
      controls (179.52 +/- 39.64 MUm, all P < 0.05). However, there was no difference
      in nasal CT between CSC and fellow eyes (P = 0.150). CONCLUSION: This result may
      suggest that manifest CSC occurs in patients with thick choroids both within and
      outside the macula, especially when subfoveal CT is increased.

PMID- 25874369
TI  - Purple pitcher plant (Sarracenia rosea) Dieback and partial community disassembly
      following experimental storm surge in a coastal pitcher plant bog.
AB  - Sea-level rise and frequent intense hurricanes associated with climate change
      will result in recurrent flooding of inland systems such as Gulf Coastal pitcher
      plant bogs by storm surges. These surges can transport salt water and sediment to
      freshwater bogs, greatly affecting their biological integrity. Purple pitcher
      plants (Sarracenia rosea) are Gulf Coast pitcher plant bog inhabitants that could
      be at a disadvantage under this scenario because their pitcher morphology may
      leave them prone to collection of saline water and sediment after a surge. We
      investigated the effects of storm surge water salinity and sediment type on S.
      rosea vitality, plant community structure, and bog soil-water conductivity. Plots
      (containing >=1 ramet of S. rosea) were experimentally flooded with fresh or
      saline water crossed with one of three sediment types (local, foreign, or no
      sediment). There were no treatment effects on soil-water conductivity;
      nevertheless, direct exposure to saline water resulted in significantly lower S.
      rosea cover until the following season when a prescribed fire and regional
      drought contributed to the decline of all the S. rosea to near zero percent
      cover. There were also significant differences in plant community structure
      between treatments over time, reflecting how numerous species increased in
      abundance and a few species decreased in abundance. However, in contrast to S.
      rosea, most of the other species in the community appeared resilient to the
      effects of storm surge. Thus, although the community may be somewhat affected by
      storm surge, those few species that are particularly sensitive to the storm surge
      disturbance will likely drop out of the community and be replaced by more
      resilient species. Depending on the longevity of these biological legacies, Gulf
      Coastal pitcher plant bogs may be incapable of fully recovering if they become
      exposed to storm surge more frequently due to climate change. 

PMID- 25874370
TI  - A Single Bout of Aerobic Exercise Reduces Anxiety Sensitivity But Not Intolerance
      of Uncertainty or Distress Tolerance: A Randomized Controlled Trial.
AB  - Several mechanisms have been posited for the anxiolytic effects of exercise,
      including reductions in anxiety sensitivity through interoceptive exposure.
      Studies on aerobic exercise lend support to this hypothesis; however, research
      investigating aerobic exercise in comparison to placebo, the dose-response
      relationship between aerobic exercise anxiety sensitivity, the efficacy of
      aerobic exercise on the spectrum of anxiety sensitivity and the effect of aerobic
      exercise on other related constructs (e.g. intolerance of uncertainty, distress
      tolerance) is lacking. We explored reductions in anxiety sensitivity and related
      constructs following a single session of exercise in a community sample using a
      randomized controlled trial design. Forty-one participants completed 30 min of
      aerobic exercise or a placebo stretching control. Anxiety sensitivity,
      intolerance of uncertainty and distress tolerance were measured at baseline, post
      intervention and 3-day and 7-day follow-ups. Individuals in the aerobic exercise
      group, but not the control group, experienced significant reductions with
      moderate effect sizes in all dimensions of anxiety sensitivity. Intolerance of
      uncertainty and distress tolerance remained unchanged in both groups. Our trial
      supports the efficacy of aerobic exercise in uniquely reducing anxiety
      sensitivity in individuals with varying levels of the trait and highlights the
      importance of empirically validating the use of aerobic exercise to address
      specific mental health vulnerabilities. Aerobic exercise may have potential as a
      temporary substitute for psychotherapy aimed at reducing anxiety-related
      psychopathology.

PMID- 25874371
TI  - Correction: reactivation of latent tuberculosis in cynomolgus macaques infected
      with SIV is associated with early peripheral T cell depletion and not virus load.

PMID- 25874372
TI  - Statin-conferred enhanced cellular resistance against bacterial pore-forming
      toxins in airway epithelial cells.
AB  - Statins are widely used to prevent cardiovascular disease. In addition to their
      inhibitory effects on cholesterol synthesis, statins have beneficial effects in
      patients with sepsis and pneumonia, although molecular mechanisms have mostly
      remained unclear. Using human airway epithelial cells as a proper in vitro model,
      we show that prior exposure to physiological nanomolar serum concentrations of
      simvastatin (ranging from 10-1,000 nM) confers significant cellular resistance to
      the cytotoxicity of pneumolysin, a pore-forming toxin and the main virulence
      factor of Streptococcus pneumoniae. This protection could be demonstrated with a
      different statin, pravastatin, or on a different toxin, alpha-hemolysin.
      Furthermore, through the use of gene silencing, pharmacological inhibitors,
      immunofluorescence microscopy, and biochemical and metabolic rescue approaches,
      we demonstrate that the mechanism of protection conferred by simvastatin at
      physiological nanomolar concentrations could be different from the canonical
      mevalonate pathways seen in most other mechanistic studies conducted with statins
      at micromolar levels. All of these data are integrated into a protein synthesis
      dependent, calcium-dependent model showing the interconnected pathways used by
      statins in airway epithelial cells to elicit an increased resistance to pore
      forming toxins. This research fills large gaps in our understanding of how
      statins may confer host cellular protection against bacterial infections in the
      context of airway epithelial cells without the confounding effect from the
      presence of immune cells. In addition, our discovery could be potentially
      developed into a host-centric strategy for the adjuvant treatment of pore-forming
      toxin associated bacterial infections. 

PMID- 25874374
TI  - Further tests of belief-importance theory.
AB  - Belief-importance (belimp) theory hypothesizes that personality traits confer a
      propensity to perceive convergences or divergences between the belief that we can
      attain certain goals and the importance that we place on these goals. Belief and
      importance are conceptualized as two coordinates, together defining the belimp
      plane. We tested fundamental aspects of the theory using four different planes
      based on the life domains of appearance, family, financial security, and
      friendship as well as a global plane combining these four domains. The criteria
      were from the areas of personality (Big Five and trait emotional intelligence)
      and learning styles. Two hundred and fifty eight participants were allocated into
      the four quadrants of the belimp plane (Hubris, Motivation, Depression, and
      Apathy) according to their scores on four reliable instruments. Most hypotheses
      were supported by the data. Results are discussed with reference to the stability
      of the belimp classifications under different life domains and the relationship
      of the quadrants with the personality traits that are hypothesized to underpin
      them. 

PMID- 25874373
TI  - Heart failure in a cohort of patients with chronic kidney disease: the GCKD
      study.
AB  - BACKGROUND AND AIMS: Chronic kidney disease (CKD) is a risk factor for
      development and progression of heart failure (HF). CKD and HF share common risk
      factors, but few data exist on the prevalence, signs and symptoms as well as
      correlates of HF in populations with CKD of moderate severity. We therefore aimed
      to examine the prevalence and correlates of HF in the German Chronic Kidney
      Disease (GCKD) study, a large observational prospective study. METHODS AND
      RESULTS: We analyzed data from 5,015 GCKD patients aged 18-74 years with an
      estimated glomerular filtration rate (eGFR) of <60 ml/min/1.73m2 or with an eGFR
      >=60 and overt proteinuria (>500 mg/d). We evaluated a definition of HF based on
      the Gothenburg score, a clinical HF score used in epidemiological studies
      (Gothenburg HF), and self-reported HF. Factors associated with HF were identified
      using multivariable adjusted logistic regression. The prevalence of Gothenburg HF
      was 43% (ranging from 24% in those with eGFR >90 to 59% in those with eGFR<30
      ml/min/1.73m2). The corresponding estimate for self-reported HF was 18% (range 5%
      24%). Lower eGFR was significantly and independently associated with the
      Gothenburg definition of HF (p-trend <0.001). Additional significantly associated
      correlates included older age, female gender, higher BMI, hypertension, diabetes
      mellitus, valvular heart disease, anemia, sleep apnea, and lower educational
      status. CONCLUSIONS: The burden of self-reported and Gothenburg HF among patients
      with CKD is high. The proportion of patients who meet the criteria for Gothenburg
      HF in a European cohort of patients with moderate CKD is more than twice as high
      as the prevalence of self-reported HF. However, because of the shared signs,
      symptoms and medications of HF and CKD, the Gothenburg score cannot be used to
      reliably define HF in CKD patients. Our results emphasize the need for early
      screening for HF in patients with CKD.

PMID- 25874375
TI  - Source apportionment and risk assessment of emerging contaminants: an approach of
      pharmaco-signature in water systems.
AB  - This paper presents a methodology based on multivariate data analysis for
      characterizing potential source contributions of emerging contaminants (ECs)
      detected in 26 river water samples across multi-scape regions during dry and wet
      seasons. Based on this methodology, we unveil an approach toward potential source
      contributions of ECs, a concept we refer to as the "Pharmaco-signature."
      Exploratory analysis of data points has been carried out by unsupervised pattern
      recognition (hierarchical cluster analysis, HCA) and receptor model (principal
      component analysis-multiple linear regression, PCA-MLR) in an attempt to
      demonstrate significant source contributions of ECs in different land-use zone.
      Robust cluster solutions grouped the database according to different EC profiles.
      PCA-MLR identified that 58.9% of the mean summed ECs were contributed by domestic
      impact, 9.7% by antibiotics application, and 31.4% by drug abuse. Diclofenac,
      ibuprofen, codeine, ampicillin, tetracycline, and erythromycin-H2O have
      significant pollution risk quotients (RQ>1), indicating potentially high risk to
      aquatic organisms in Taiwan. 

PMID- 25874376
TI  - Platelet parameters and (1, 3)-beta-D-glucan as a diagnostic and prognostic
      marker of invasive fungal disease in preterm infants.
AB  - The diagnosis of neonatal invasive fungal disease (IFD) is difficult and often
      delayed. The platelet parameters and (1, 3)-beta-D-Glucan (BG) may be useful for
      diagnosing IFD, but their diagnostic performance are not well characterized in
      neonates. We studied 63 preterm infants with IFD, 160 preterm infants without
      sepsis (preterm control), and 41 preterm infants with bacterial sepsis. Platelet
      parameters at the first day of onset of IFD and at the fourteenth day after
      antifungal treatment were evaluated. Serum BG was measured. Platelet count (PC),
      plateletcrit (PCT), and platelet distribution width (PDW) values were
      significantly lower, and mean platelet volume (MPV) values significantly higher
      in the IFD versus preterm control infants. PC and PCT values were much lower in
      infants with IFD versus bacterial sepsis, and there were significant differences
      in BG value between the two groups. After 14 days of antifungal treatment,
      significant elevations in PC, PCT, PDW and reductions in MPV levels in IFD group
      were observed. Receiver operating characteristic (ROC) curves showed that PC and
      PCT were strong predictors of IFD. The PC and PCT cut-offs for predicting IFD
      were 119.5 (sensitivity 78%, specificity 95%) and 0.21 (sensitivity 83%,
      specificity 85%), respectively. There were significant differences in PC and PCT
      levels between deceased and survived patients. The PC and PCT cut-offs for
      predicting deceased IFD were 39 (sensitivity 62%, specificity 86%) and 0.04
      (sensitivity 50%, specificity 95%), respectively. The sensitivity in diagnosing
      IFD by a BG cutoff of >=10 pg/ml was 68.3% and specificity was 75.6%. PC and PCT
      levels in the BG >=400 pg/ml group were significantly lower compared to the
      BG<400 pg/ml group. Platelet parameters and BG could be useful biomarkers for the
      diagnosis and prognosis of neonatal IFD.

PMID- 25874379
TI  - Axial growth and fusion of liposome regulated by macromolecular crowding and
      confinement.
AB  - The endomembrane system, including the endoplasmic reticulum, Golgi apparatus,
      lysosomes, and endosomes, is located in the crowded intracellular environment. An
      understanding of the cellular structure and functions requires knowledge of how
      macromolecular crowding and confinement affect the activity of membrane and its
      proteins. Using negatively charged liposome and the peptide K3L8K3 as a model
      system, we studied the aggregation behavior of liposome in a matrix of
      polyacrylamide and hyaluronic acid. Without matrix, the liposomes form spherical
      aggregates in the presence of K3L8K3. However, they orient in one dimension and
      fuse into a tube up to 40 MUm long in the matrix. The growth of the tube is via
      end-to-end connection. This anisotropic growth is mainly due to the
      macromolecular confinement provided by the polymer network. The study of the
      interactions between liposome and peptide in the crowded environment helps to
      reveal the mechanism of membrane-related processes in vivo. 

PMID- 25874377
TI  - A meiotic mystery: How sister kinetochores avoid being pulled in opposite
      directions during the first division.
AB  - We now take for granted that despite the disproportionate contribution of females
      to initial growth of their progeny, there is little or no asymmetry in the
      contribution of males and females to the eventual character of their shared
      offspring. In fact, this key insight was only established towards the end of the
      eighteenth century by Joseph Koelreuter's pioneering plant breeding experiments.
      If males and females supply equal amounts of hereditary material, then the latter
      must double each time an embryo is conceived. How then does the amount of this
      mysterious stuff not multiply exponentially from generation to generation? A
      compensatory mechanism for diluting the hereditary material must exist, one that
      ensures that if each parent contributes one half, each grandparent contributes a
      quarter, and each great grandparent merely an eighth. An important piece of the
      puzzle of how hereditary material is diluted at each generation has been
      elucidated over the past ten years. 

PMID- 25874378
TI  - The hyperornithinemia-hyperammonemia-homocitrullinuria syndrome.
AB  - BACKGROUND: Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome is
      a rare autosomal recessive disorder of the urea cycle. HHH has a panethnic
      distribution, with a major prevalence in Canada, Italy and Japan. Acute clinical
      signs include intermittent episodes of vomiting, confusion or coma and hepatitis
      like attacks. Alternatively, patients show a chronic course with aversion for
      protein rich foods, developmental delay/intellectual disability, myoclonic
      seizures, ataxia and pyramidal dysfunction. HHH syndrome is caused by impaired
      ornithine transport across the inner mitochondrial membrane due to mutations in
      SLC25A15 gene, which encodes for the mitochondrial ornithine carrier ORC1. The
      diagnosis relies on clinical signs and the peculiar metabolic triad of
      hyperammonemia, hyperornithinemia, and urinary excretion of homocitrulline. HHH
      syndrome enters in the differential diagnosis with other inherited or acquired
      conditions presenting with hyperammonemia. METHODS: A systematic review of
      publications reporting patients with HHH syndrome was performed. RESULTS: We
      retrospectively evaluated the clinical, biochemical and genetic profile of 111
      HHH syndrome patients, 109 reported in 61 published articles, and two unpublished
      cases. Lethargy and coma are frequent at disease onset, whereas pyramidal
      dysfunction and cognitive/behavioural abnormalities represent the most common
      clinical features in late-onset cases or during the disease course. Two common
      mutations, F188del and R179* account respectively for about 30% and 15% of
      patients with the HHH syndrome. Interestingly, the majority of mutations are
      located in residues that have side chains protruding into the internal pore of
      ORC1, suggesting their possible interference with substrate translocation. Acute
      and chronic management consists in the control of hyperammonemia with protein
      restricted diet supplemented with citrulline/arginine and ammonia scavengers.
      Prognosis of HHH syndrome is variable, ranging from a severe course with
      disabling manifestations to milder variants compatible with an almost normal
      life. CONCLUSIONS: This paper provides detailed information on the clinical,
      metabolic and genetic profiles of all HHH syndrome patients published to date.
      The clinical phenotype is extremely variable and its severity does not correlate
      with the genotype or with recorded ammonium/ornithine plasma levels. Early
      intervention allows almost normal life span but the prognosis is variable,
      suggesting the need for a better understanding of the still unsolved
      pathophysiology of the disease.

PMID- 25874380
TI  - Circulating endothelial progenitor cells and the risk of vascular events after
      ischemic stroke.
AB  - BACKGROUND AND PURPOSE: We evaluated the hypothesis that the number of
      circulating EPC could be associated with the risk of stroke recurrence (SR) or
      vascular events (VE) after an ischemic stroke. METHODS: We studied prospectively
      consecutive patients with cerebral infarction within the first 48 hours after the
      onset. We recorded demographic factors, vascular risk factors, previous Rankin
      scale (RS) score, and etiology. We analyzed EPC counts by flow cytometry in blood
      collected at day 7 and defined EPC as CD34+/CD133+/KDR+ cells. Mean follow-up was
      29.3 +/- 16 months. We evaluated SR as well as VE. Patients were classified as to
      the presence or absence of EPC in the circulation (either EPC+ or EPC-).
      Bivariate analyses, Kaplan-Meier survival curves and Cox regression models were
      used. RESULTS: We included 121 patients (mean age 70.1+/-12.6 years; 65% were
      men). The percentage of EPC+ patients was 47.1%. SR occurred in 12 (9.9%) and VE
      in 18 (14.9%) patients. SR was associated significantly with a worse prior RS
      score, previous stroke and etiology, but not with EPC count. VE were associated
      significantly with EPC-, worse prior RS score, previous stroke, high age,
      peripheral artery disease and etiology. Cox regression model showed that EPC- (HR
      7.07, p=0.003), age (HR 1.08, p=0.004) and a worse prior RS score (HR 5.8,
      p=0.004) were associated significantly with an increased risk of VE. CONCLUSIONS:
      The absence of circulating EPC is not associated with the risk of stroke
      recurrence, but is associated with an increased risk of future vascular events.

PMID- 25874381
TI  - Has Madagascar lost its exceptional leptospirosis free-like status?
AB  - BACKGROUND: Leptospirosis is a widespread but underreported cause of morbidity
      and mortality. It has rarely been reported in either humans or animals in
      Madagascar. METHODS: We conducted a cross-sectional survey of the inhabitants in
      Moramanga, Madagascar, in June 2011, to estimate the prevalence of human
      infection using the microscopic agglutination test (MAT). This activity was
      carried out as part of a workshop implemented by the Pasteur Institute of
      Madagascar, focusing on surveillance with a one week field study and targeting
      the health staff of the district level. RESULTS: In total, we sampled 678
      inhabitants from 263 households. The sex ratio (M/F) was 0.65 and the mean age
      26.7 years. We obtained a value of 2.9% for the first recorded seroprevalence of
      this disease in the human community of Moramanga. Questionnaire responses
      revealed frequent contacts between humans and rodents in Moramanga. However,
      activities involving cattle were identified as a risk factor significantly
      associated with seropositivity (OR=3). CONCLUSION: Leptospirosis remains a
      neglected disease in Madagascar. This study highlights the need to quantify the
      public health impact of this neglected disease in a more large scale, in all the
      country and to establish point-of-care laboratories in remote areas.

PMID- 25874382
TI  - Two Stepwise Synthetic Routes toward a Hetero[4]rotaxane.
AB  - Heterorotaxanes have been emerging as an important class of mechanically
      interlocked molecules and have attracted much attention in recent years. Driven
      by the distinguishable host-guest interactions between crown ether macrocycles
      and ammonium with different sizes, a novel hetero[4]rotaxane was successfully
      prepared by employing the combination of copper-catalyzed "click" reaction and
      P(n-Bu)3-catalyzed esterification reaction as stoppering reactions. The
      hetero[4]rotaxane contains an interlocked species in which a dibenzo[24]crown-8
      ring threaded by a dibenzylammonium-containing component with two benzo[21]crown
      7 macrocycles at both ends to act as stoppers, and each of the two benzo[21]crown
      7 rings is also threaded with a benzylalkylammonium unit to form the second
      interlocked species. The hetero[4]rotaxane was prepared through two different
      stepwise synthetic routes, and the complicated chemical structure of the
      hetero[4]rotaxane was well-characterized by (1)H NMR spectroscopy and high
      resolution electrospray ionization (HR-ESI) mass spectrometry. The investigation
      shows that the construction of complicated topological heterorotaxane can be
      achieved via distinct approaches with high efficiencies, which may provide a
      foundation for the construction of more sophisticated heterorotaxane systems or
      functional supermolecules. 

PMID- 25874384
TI  - Meta-Analysis of Theory of Mind and Peer Popularity in the Preschool and Early
      School Years.
AB  - It has been argued that children who possess an advanced theory of mind (ToM) are
      viewed positively by their peers, but the empirical findings are mixed. This meta
      analysis of 20 studies including 2,096 children (aged from 2 years, 8 months to
      10 years) revealed a significant overall association (r = .19) indicating that
      children with higher ToM scores were also more popular in their peer group. The
      effect did not vary with age. The effect was weaker for boys (r = .12) compared
      to girls (r = .30). ToM was more strongly associated with popularity (r = .23)
      than with rejection (r = .13). These findings confirm that ToM development has
      significant implications for children's peer relationships.

PMID- 25874383
TI  - Metaproteomics of complex microbial communities in biogas plants.
AB  - Production of biogas from agricultural biomass or organic wastes is an important
      source of renewable energy. Although thousands of biogas plants (BGPs) are
      operating in Germany, there is still a significant potential to improve yields,
      e.g. from fibrous substrates. In addition, process stability should be optimized.
      Besides evaluating technical measures, improving our understanding of microbial
      communities involved into the biogas process is considered as key issue to
      achieve both goals. Microscopic and genetic approaches to analyse community
      composition provide valuable experimental data, but fail to detect presence of
      enzymes and overall metabolic activity of microbial communities. Therefore,
      metaproteomics can significantly contribute to elucidate critical steps in the
      conversion of biomass to methane as it delivers combined functional and
      phylogenetic data. Although metaproteomics analyses are challenged by sample
      impurities, sample complexity and redundant protein identification, and are still
      limited by the availability of genome sequences, recent studies have shown
      promising results. In the following, the workflow and potential pitfalls for
      metaproteomics of samples from full-scale BGP are discussed. In addition, the
      value of metaproteomics to contribute to the further advancement of microbial
      ecology is evaluated. Finally, synergistic effects expected when metaproteomics
      is combined with advanced imaging techniques, metagenomics, metatranscriptomics
      and metabolomics are addressed. 

PMID- 25874385
TI  - Cardioprotective effects of fucoidan against hypoxia-induced apoptosis in H9c2
      cardiomyoblast cells.
AB  - CONTEXT: Cardiomyocyte apoptosis plays a critical role in the progress of heart
      diseases. Fucoidan, a complex-sulfated polysaccharide, has been reported to
      possess potential cardioprotective efficacy in vivo. OBJECTIVE: The present study
      determines whether fucoidan could provide cardioprotection on hypoxia-induced
      cardiomyocyte apoptosis. MATERIALS AND METHODS: H9c2 cardiomyoblast cells were
      incubated with various concentrations (15, 30, and 60 MUg/ml) of fucoidan in a
      humidified incubator at 37  degrees C with 95% O2 and 5% CO2. After 6 h, hypoxia
      was processed and the cardioprotective effects of fucoidan were evaluated by
      applying MTT, ELISA, Hoechst 33258 nucleus staining, and western blot. RESULTS:
      Following a 6 h exposure of H9c2 to hypoxic condition, significant reduction was
      found in cell survival (0.57-fold) and superoxide dismutase (SOD) activity (0.56
      fold), which were associated with the increase of malondialdehyde (MDA) level
      (2.58-fold), creatine phosphokinase (CK, 3.57-fold), and lactate dehydrogenase
      (LDH) activities (2.39-fold). Moreover, hypoxia-induced apoptosis was confirmed
      by Hoechst 33258 nuclear staining, and these changes were accompanied by the
      increase of Bcl-2 (1.27-fold) and Bax expression (2.6-fold). However,
      preincubation of the cells with fucoidan prior to hypoxia exposure elevated the
      cell viability (30 MUg/ml, 1.18-fold; 60 MUg/ml, 1.32-fold) and SOD activity (30
      MUg/ml, 1.12-fold; 60 MUg/ml, 1.25-fold), but decreased the MDA level (30 MUg/ml,
      0.70-fold; 60 MUg/ml, 0.80-fold), CK (30 MUg/ml, 0.69-fold; 60 MUg/ml, 0.76
      fold), and LDH (30 MUg/ml, 0.67-fold; 60 MUg/ml, 0.86-fold) leakages. Hoechst
      33258 nuclear staining observations demonstrated the same protective effect of
      fucoidan on hypoxia-induced myocardial injury. Also, cardioprotective effects of
      fucoidan were reflected by increasing Bcl-2 (60 MUg/ml, 1.84-fold), as well as
      decreasing Bax (60 MUg/ml, 0.6-fold). CONCLUSION: Fucoidan had protective effect
      against hypoxia-induced cardiomyocytes apoptosis, and the mechanism might involve
      protections of the cell from oxidative injury.

PMID- 25874386
TI  - Rosmarinic acid exerts a neuroprotective effect in the kainate rat model of
      temporal lobe epilepsy: Underlying mechanisms.
AB  - CONTEXT: Temporal lobe epilepsy (TLE) is an intractable neurological disorder.
      Rosmarinic acid (RA) is a natural polyphenol with antioxidant, anti-apoptotic,
      and anti-inflammatory properties. OBJECTIVE: This study evaluates beneficial
      effect of RA in intrahippocampal kainate-induced model of TLE. MATERIALS AND
      METHODS: Rats were divided into sham, RA-pretreated sham, kainate, and sodium
      valproate (VA) or RA-pretreated kainate groups. Rats received RA or VA p.o. at
      doses of 10 or 300 mg/kg/d, respectively, starting 1 week before the surgery.
      After 6 weeks, seizure intensity, apoptosis, and oxidative stress markers were
      evaluated in addition to determination of Timm index as an indicator of mossy
      fiber sprouting (MFS) and the number of Nissl-stained neurons. RESULTS: All rats
      in the kainate group had seizure and 24.3% of rats in the kainate + VA group and
      36.7% of rats in the kainate + RA group showed seizure. The kainate group had a
      significant elevation of malondialdehyde (MDA) (p < 0.05) and nitrite (p < 0.01)
      and reduction of glutathione (GSH) and catalase activity (p < 0.05) and
      pretreatment of kainate-lesioned rats with RA or VA significantly lowered MDA and
      nitrite content (p < 0.05) and raised activity of catalase (p < 0.05). The
      kainate group also had a significant reduction of neurons in CA1 and CA3 regions
      and an elevation of Timm index (p < 0.05-0.001) and RA or VA significantly (p <
      0.05-0.01) prevented these changes. DISCUSSION AND CONCLUSION: RA could attenuate
      seizure, mitigates oxidative stress, augments the activity of defensive systems,
      and prevent hippocampal neuronal loss and MFS in the kainate model of TLE.

PMID- 25874387
TI  - Biological activities and DNA interactions of Amanita ovoidea.
AB  - CONTEXT: Amanita ovoidea (Bull.) Link (Amanitaceae) is a well-known species due
      to its pleasant aroma and flavor since ancient times in the worldwide. This
      species is also known in Turkey and people consume it extensively. OBJECTIVE: To
      evaluate medicinal importance of A. ovoidea for human health, to explain the
      effect of mushroom extracts on bacterial DNA, and to find preventive role on
      bacterial disease. MATERIALS AND METHODS: Chloroform, acetone, and methanol
      extracts of A. ovoidea were tested for the antimicrobial activities against four
      Gram-positive bacteria, five Gram-negative bacteria, and yeast using a micro
      dilution method. In addition, DNA binding, DNA cleavage activity, and restriction
      enzyme digestion of the methanol extract of A. ovoidea were examined at different
      concentrations (40.000-78.125 ug/mL). RESULTS: The highest minimum inhibitory
      concentration (MIC) value observed against the test micro-organisms was with the
      chloroform extract (MIC 19.5 ug/mL concentration) against Candida albicans. Other
      highest antimicrobial effects observed against the test micro-organisms were with
      the methanol extracts against Bacillus subtilis, Staphylococcus aureus, Listeria
      monocytogenes, Streptococcus pyogenes, Candida albicans, Klebsiella pneumoniae,
      Proteus vulgaris, and Salmonella enteritidis (MICs, 78 ug/mL concentrations). All
      concentrations reduced the mobility of plasmid DNA. BamHI and HindIII targeted
      specially to supercoils and cut them. Amanita ovoidea extract prevented cutting
      with HindIII by binding especially to the AA region in open circular DNA.
      DISCUSSION AND CONCLUSION: Present results demonstrated that A. ovoidea has
      excellent antimicrobial and antifungal activities by its DNA interaction activity
      on pBR322.

PMID- 25874389
TI  - [Pertrochanteric femur fracture - our technique and results].
AB  - BACKGROUND: In patients over 65 years, pertrochanteric proximal femur fractures
      are very common, with an incidence of 966/100,000. Treatment of choice is nailing
      or dynamic hip screws. The operative approaches are standardised and easy to
      learn. PURPOSE: We want to demonstrate the operation technique by video and our
      own results of the last two years. PATIENTS: From 1 January 2012 until 31
      December 2013, 210 patients with an average age of 80.7 years and pertrochanteric
      fractures underwent treatment. RESULTS: Preoperative delay averaged one day. Skin
      to skin operative time averaged 48 minutes. There were 6 misplaced implants and
      cutouts (2.8 %), one infection (0.5 %), and 6 operative revisions because of
      hematoma or seroma (2.8 %). Four patients (1.9 %) died of cardiovascular failure
      with ASA 3 and 4 during the inpatient stay. CONCLUSION: Internal fixation with
      nailing in pertrochanteric femur fractures is a standard operative approach. It
      is quickly learnt and easily performed.

PMID- 25874390
TI  - [Quality in arthroplasty].

PMID- 25874388
TI  - In vivo and in vitro characterization of a Plasmodium liver stage-specific
      promoter.
AB  - Little is known about stage-specific gene regulation in Plasmodium parasites, in
      particular the liver stage of development. We have previously described in the
      Plasmodium berghei rodent model, a liver stage-specific (lisp2) gene promoter
      region, in vitro. Using a dual luminescence system, we now confirm the stage
      specificity of this promoter region also in vivo. Furthermore, by substitution
      and deletion analyses we have extended our in vitro characterization of important
      elements within the promoter region. Importantly, the dual luminescence system
      allows analyzing promoter constructs avoiding mouse-consuming cloning procedures
      of transgenic parasites. This makes extensive mutation and deletion studies a
      reasonable approach also in the malaria mouse model. Stage-specific expression
      constructs and parasite lines are extremely valuable tools for research on
      Plasmodium liver stage biology. Such reporter lines offer a promising opportunity
      for assessment of liver stage drugs, characterization of genetically attenuated
      parasites and liver stage-specific vaccines both in vivo and in vitro, and may be
      key for the generation of inducible systems. 

PMID- 25874391
TI  - [Taking the anamnesis with a questionnaire - safe and effective].
AB  - INTRODUCTION: The anamnesis is essential for the treatment of any patient. On the
      other hand, the data are often of poor quality. The aim of the study was to work
      out whether a questionnaire which is filled out by the patient him-/herself is a
      reasonable tool for data acquisition. METHODS: In a level-IV trauma centre the
      data acquisition of 50 consecutive patients was performed with a questionnaire
      which was checked by a doctor. Excluding criteria were an age < 18 years,
      previous treatment in the clinic, a transfer from an external clinic or a caring
      institution and a dementia. The results were compared with the data of the 50
      patients prior to the study start. RESULTS: We collected data about the general
      doctor, diseases, allergies, tobacco usage, drugs, operations and the familial
      situation. In all 7 fields the questionnaire raised more data than the oral
      survey; in 4 sections the difference was significant, in 3 (p > 0.05).
      DISCUSSION: A questionnaire is a reasonable, time-sparing tool for data
      acquisition of the individual anamnesis in a surgical clinic.

PMID- 25874392
TI  - [Bone cement adhesion on ceramic surfaces - surface activation of retention
      surfaces of knee prostheses by atmospheric plasma versus thermal surface
      treatment].
AB  - AIM: CoCrMo alloys are contraindicated for allergy sufferers. For these patients,
      uncemented and cemented prostheses made of titanium alloy are indicated. Knee
      prostheses machined from that alloy, however, may have poor tribological
      behaviour, especially in relation to UHMWPE inlays. Therefore, for knee
      replacement cemented high-strength oxide ceramic prostheses are suitable for
      allergy sufferers and in cases of particle-induced aseptic loosening. For
      adhesion of bone cement, the ceramic surface, however, only exposes inefficient
      mechanical retention spots as compared with a textured metal surface. Undercuts
      generated by corundum blasting which in the short-term are highly efficient on a
      CoCrMo surface are not possible on a ceramic surface due to the brittleness of
      ceramics. Textures due to blasting may initiate cracks which will weaken the
      strength of a ceramic prosthesis. Due to the lack of textures mechanical
      retention is poor or even not existent. Micromotions are promoted and early
      aseptic loosening is predictable. Instead silicoating of the ceramic surface will
      allow specific adhesion and result in better hydrolytic stability of bonding
      thereby preventing early aseptic loosening. Silicoating, however, presupposes a
      clean and chemically active surface which can be achieved by atmospheric plasma
      or thermal surface treatment. METHOD: In order to evaluate the effectiveness of
      silicoating the bond strengths of atmospheric plasma versus thermal surface
      treated and silicate layered ZPTA surfaces were compared with "as-fired" surfaces
      by utilising TiAlV probes (diameter 6 mm) for traction-adhesive strength tests.
      After preparing samples for traction-adhesive strength tests (sequence: ceramic
      substrate, silicate and silane, protective lacquer [PolyMA], bone cement, TiAlV
      probe) they were aged for up to 150 days at 37  degrees C in Ringer's solution.
      RESULTS: The bond strengths observed for all ageing intervals were well above 20
      MPa and much higher and more hydrolytically stable for silicate layered compared
      with "as-fired" ZPTA samples. CONCLUSION: Silicoating may be effective for
      achieving high initial bond strength of bone cement on surfaces of oxide ceramics
      and also suitable to stabilise bond strength under hydrolytic conditions as
      present in the human body in the long-term. Activation by atmospheric plasma or
      thermal surface treatment seems to be effective for activation prior to
      silicoating. Due the proposed silicate layer migration, micromotions and
      debonding should be widely reduced or even eliminated.

PMID- 25874393
TI  - [Suprapectoral mini-open biceps tenodesis - functional and sonographic results].
AB  - BACKGROUND: Aim of this study was to evaluate the effectiveness of a
      suprapectoral mini-open tenodesis of the long head of the biceps (LHB) tendon
      with ultrasound assessment. Secondary aim was to compare the results of an
      extraosseous fixation (group I) to those of an intraosseous fixation technique
      (group II). PATIENTS AND METHODS: 25 patients (10 female, 15 male) aged 54 +/- 8
      (36 to 68) years were followed-up 21 +/- 4.7 (13 to 32) months postoperatively.
      Tenodesis fixation was extraosseous in 12 (group I) and intraosseous in 13
      patients (group II). Preoperative shoulder function and intraoperative findings
      were recorded. At the time of follow-up the fixation of the biceps tendon was
      evaluated by ultrasound examination. Furthermore, the shoulder function, the
      simple shoulder test (SST), the Constant-Murley score (CMS) and the "long head of
      the biceps (LHB) score" were assessed. RESULTS: Failure of tenodesis fixation was
      observed in 3/12 cases (25 %) of group I and 1/13 cases (8 %) of group II.
      Shoulder flexion (p < 0.001), abduction (p < 0.001), external rotation (p <
      0.001) and the pain level (p < 0.001) improved significantly compared to the
      preoperative status. At time of follow-up the CMS averaged 79.4 +/- 13 points,
      the age and gender related CMS averaged 95.7 +/- 16.4 %. Mean SST was 10.6 +/-
      2.1 points. No significant difference (p = 0.064) could be observed between the
      LHB of the affected (88.1 +/- 9.7) versus the non-affected shoulder (92.7 +/-
      13.6 points). Age and gender related CMS (p = 0.96), LHB score (p = 0.16) and SST
      (p = 0.94) of both groups revealed no significant differences. CONCLUSION: The
      intraosseous fixation technique seems favourable with less fixation failure
      compared to the extraosseous suspension technique. The suprapectoral mini-open
      tenodesis of the LHB is a valuable alternative tenodesis technique with good to
      excellent clinical results.

PMID- 25874394
TI  - [Comparison of stability of plate fixateurs with parallel and oblique screw
      directions].
AB  - INTRODUCTION: One of the main failure mechanisms of modern plate fixateurs is the
      tearing of the whole plate-screw construct out of the osteoporotic bone. The aim
      of this study was to show whether an oblique screw placement can improve the
      fixation of the plate to the bone. METHODS: A steel probe was fixed to a
      synthetic bone (Fa. Sawbones) with standard titanium fixed-angle screws in
      parallel and 55 degrees  oblique positioning. We tested the static tear force and
      the dynamic stability (force distance 1.4 or 1.6 mm, 610 and 900 N, frequency of
      force shift of 560 or 380/min). Endpoint was a visible tear of the artificial
      bone. In addition we performed a morphological analysis of the torn fragments.
      RESULTS: The maximal tear force was 2.04 kN (1.95-2.13) for oblique and 2.66 kN
      (2.55-2.77) for parallel placement (p < 0.05). With a parallel positioning a
      higher number of force shifts were performed before a visual tear appeared. With
      parallel positioning the screw canal was torn with an intact surrounding
      corticalis; in oblique positioning the threads remained intact, the corticalis
      was torn out with a wedge. DISCUSSION: An oblique screw positioning does not
      result in a higher tear force in modern plate fixateurs.

PMID- 25874395
TI  - [Adjuvant systemic antibiotic therapy for surgically treated spondylodiscitis].
AB  - Recognised methods for the treatment of spondylodiscitis in correspondence to the
      immobilisation are systemic antibiotic therapy. However, the available data for
      recommendations of specific antibiotic therapy are very heterogeneous. The aim of
      this study was to focus on the adjuvant antibiotic therapy in surgical treated
      cases of spondylodiscitis and to reach a guideline regarding its application in
      patients' spondylodiscitis. Between 01.10.1998 and 31.12.2011 276 inpatient cases
      of spondylodiscitis were surgically treated, documented and included in the
      study. The study involved medical history, germ status, localisation and extent
      of spondylodiscitis and antibiotic treatment. Between 01.01.2012 and 31.12.2013 a
      further 20 cases of spondylodiscitis were treated according to a standardised
      treatment regimen of antibiotic therapy and included in the study. The age
      distribution shows a marked prominence of 60 to 80 year-olds, with a leading
      localisation of spondylodiscitis in the lumbar spine with 55 % followed by the
      thoracic spine (33 %) and the cervical spine (12 %). A constant observation
      during the study periods was the delayed diagnosis of more than 1 month of
      spondylodiscitis, so that about 60 % of the patients were not receiving any
      treatment for their disease at the time of hospitalisation. The aetiology of
      spondylodiscitis is very heterogeneous and remained unknown in 34 % of cases.
      However, diabetes mellitus appeared as a disease favouring the occurrence of
      spondylodiscitis since it was concomitant with almost 50 % of patients with
      spondylodiscitis. The bacterial spectrum is limited in our area to staphylococci,
      with a predominance of Staphylococcus aureus. At least about 10 % of the germs
      are multi-drug resistant. In 45 % of cases, pathogen detection was unsuccessful.
      Clindamycin is the most commonly used antibiotic in the treatment of
      spondylodiscitis and is used in 26.8 % in combinations with other antibiotics.
      The antibiotic therapy is administered for at least for 3 months. The significant
      decrease in inflammatory markers in the course of treatment shows the positive
      response of patients to therapy. The recommendations for antibiotic treatment of
      spondylodiscitis are very heterogeneous, so our goal is to standardise the
      therapy without reducing the quality and effectiveness of treatment. The results
      show that the calculated antibiotic therapy (CAT) with clindamycin is reasonable
      in the treatment of spondylodiscitis especially with the predominance of
      Staphylococcus aureus as pathogen. In addition, suitable antibiotic therapy
      should be administered in correspondence to a culture and sensitivity testing and
      should be maintained for at least 12 weeks, even when a reduction of inflammatory
      markers by 50 % after 2 weeks has already been achieved. It is noteworthy to
      point out the high probability of coexistence of spondylodiscitis with diabetes
      mellitus, so that spondylodiscitis should always be considered in diabetic
      patients with back pain and increased levels of inflammatory markers. A
      significant reduction in the very long time until reaching a definitive diagnosis
      should be achieved. 

PMID- 25874396
TI  - [Is it possible to enhance our expert knowledge from Wikipedia?].
AB  - BACKGROUND: The so-called new media are always a kind of challenge for training
      supervisors, medical students and doctors-in-training. Especially Wikipedia has a
      significant position for obtaining important medical information on the internet.
      Beside many advantages of Wikipedia, there is always the doubt about the
      correctness of published articles by unknown authors. Therefore the aim of our
      survey was to investigate the relevance of Wikipedia articles about orthopaedic
      and traumatological issues in the daily clinical routine. MATERIALS AND METHODS:
      In September 2013 two different questionnaires about medical issues were given to
      medical students, resident physicians and one medical specialist. The questioning
      was about diseases/symptoms, examinations/classifications and conservative
      therapy/surgery of the department of orthopaedics and traumatology. A total of
      211 Wikipedia articles were evaluated. Additionally, the participants gave an
      subjective estimation about these articles. RESULTS: Overall 134 of 211 separate
      medical items appeared on Wikipedia. The survey has proven the up-to-dateness of
      Wikipedia articles and their listing on the first or second position on Google.
      Wikipedia contains a lot of bibliographical references, high-quality images and
      video material. Almost half (42,5 %) of all evaluated articles are appropriate
      for use in medical exams and in the daily clinical work. CONCLUSION: First and
      foremost young resident physicians, the so-called web 2.0 generation, are using
      the internet for daily work. Maybe the process of learning is developing and
      changing at the same time. Wikipedia gives the opportunity for everyone to
      acquire information for free and all over the place. The collaboration of
      everyone is necessary to improve the quality of medical issues on Wikipedia.

PMID- 25874397
TI  - [Prevention of bicycle accidents].
AB  - For a very precise analysis of all injured bicyclists in Germany it would be
      important to have definitions for "severely injured", "seriously injured" and
      "critically injured". By this, e.g., two-thirds of surgically treated bicyclists
      who are not registered by the police could become available for a general
      analysis. Elderly bicyclists (> 60 years) are a minority (10 %) but represent a
      majority (50 %) of all fatalities. They profit most by wearing a helmet and would
      be less injured by using special bicycle bags, switching on their hearing aids
      and following all traffic rules. E-bikes are used more and more (145 % more in
      2012 vs. 2011) with 600,000 at the end of 2011 and are increasingly involved in
      accidents but still have a lack of legislation. So even for pedelecs 45 with 500
      W and a possible speed of 45 km/h there is still no legislative demand for the
      use of a protecting helmet. 96 % of all injured cyclists in Germany had more than
      0.5 0/00 alcohol in their blood, 86 % more than 1.1 0/00 and 59 % more than 1.7
      0/00. Fatalities are seen in 24.2 % of cases without any collision partner.
      Therefore the ADFC calls for a limit of 1.1 0/00. Some virtual studies conclude
      that integrated sensors in bicycle helmets which would interact with sensors in
      cars could prevent collisions or reduce the severity of injury by stopping the
      cars automatically. Integrated sensors in cars with opening angles of 180 degrees
      enable about 93 % of all bicyclists to be detected leading to a high rate of
      injury avoidance and/or mitigation. Hanging lamps reduce with 35 % significantly
      bicycle accidents for children, traffic education for children and special
      trainings for elderly bicyclists are also recommended as prevention tools. As
      long as helmet use for bicyclists in Germany rates only 9 % on average and
      legislative orders for using a helmet will not be in force in the near future,
      coming up campaigns seem to be necessary to be promoted by the Deutscher
      Verkehrssicherheitsrat as, e.g., "Helmets are cool". Also, spots in TV should be
      broadcasted like "The 7th sense" or "Traffic compass", which were warning car
      drivers many years ago of moments of danger but now they could be used to warn
      bicyclists of life-threatening situations in traffic. 

PMID- 25874398
TI  - [Tripolar cups].
AB  - Tripolar cups can be separated into constrained and unconstrained dual-mobility
      cups. The latter show better survival and revision rates. The main problem is the
      polyethylene wear. Therefore modern types of polyethylene are used in these cups.
      The indications for dual-mobility cups are recurrent dislocation and situations
      where the risk of dislocation is increased. 

PMID- 25874399
TI  - [Retention of the prosthesis in early periprosthetic infection after total hip
      arthroplasty].
AB  - BACKGROUND: The rate of periprosthetic infection after total hip arthroplasty
      (THA) without patient-specific risk factors is about 1 %. The therapeutic
      challenges are control of infection, restoration of hip function and prevention
      of reinfection. In early infection, "irrigation and debridement" (I&D) with
      exchange of mobile components and retention of the prosthesis remains an
      attractive alternative to one- or two-stage revision. However, variable results
      have been reported in the literature. Recent studies have shown new algorithms of
      treatment for early infection and acute haematogenous infection after THA.
      PATIENTS AND METHODS: Recent therapeutic algorithms for early infections after
      THA and an overview of the literature are presented. We conducted a retrospective
      analysis of 73 patients with early postoperative infection or acute haematogenous
      infection (symptoms shorter than 4 weeks) after THA who were treated with I&D,
      exchange of mobile components and retention of the prosthesis at our hospital
      between 2002 and 2011. RESULTS: RESULTS from the recent literature have shown
      that the treatment concept of prosthetic retention can only be successful within
      a maximum time of symptoms of 3 weeks in cases of haematogenous infection and a
      maximum time span of 4 weeks after index operation in cases of early infection.
      In our retrospective study with 73 patients, the treatment was successful (free
      of infection) in 46 patients (63 %). A persistence of infection occurred in 27
      patients (37 %). "Difficult to treat" bacteria were present in 28.8 % of the
      patients. CONCLUSION: The concept of irrigation and debridement with retention of
      the prosthesis is a valuable alternative to one- or two-stage revision THA, if a
      maximum time of 4 weeks after index operation in early infections and a maximum
      time of symptoms of 3 weeks in haematogenous infections are not exceeded.
      However, reinfection rates after I&D are higher than after two-stage procedures.
      Prerequisites for success of the I&D algorithm are a stable prosthesis, operable
      soft tissues, and germs susceptible to antibiotic treatment.

PMID- 25874400
TI  - [Ceramic-on-ceramic bearings in total hip arthroplasty (THA)].
AB  - The main reason for total hip arthroplasty (THA) revision is the wear-related
      aseptic loosening. Younger and active patients after total joint replacement
      create high demands, in particular, on the bearings. The progress, especially for
      alumina ceramic-on-ceramic bearings and mixed ceramics have solved many problems
      of the past and lead to good in vitro results. Modern ceramics (alumina or mixed
      ceramics containing alumina) are extremely hard, scratch-resistant,
      biocompatible, offer a low coefficient of friction, superior lubrication and have
      the lowest wear rates in comparison to all other bearings in THA. The
      disadvantage of ceramic is the risk of material failure, i.e., of ceramic
      fracture. The new generation of mixed ceramics (delta ceramic), has reduced the
      risk of head fractures to 0.03-0.05 %, but the risk for liner fractures remains
      unchanged at about 0.02 %. Assuming a non-impinging component implantation,
      ceramic-on-ceramic bearings have substantial advantages over all other bearings
      in THA. Due to the superior hardness, ceramic bearings produce less third body
      wear and are virtually impervious to damage from instruments during the
      implantation process. A specific complication for ceramic-on-ceramic bearings is
      "squeaking". The high rate of reported squeaking (0.45 to 10.7 %) highlights the
      importance of precise implant positioning and the stem and patient selection.
      With precise implant positioning this problem is rare with many implant designs
      and without clinical relevance. The improved tribology and the presumable
      resulting implant longevity make ceramic-on-ceramic the bearing of choice for
      young and active patients. 

PMID- 25874401
TI  - [A novel technique for a stable intramedullary fixation of static spacers in two
      stage septic revision TKA with severe bone defects].
AB  - BACKGROUND: Articulating as well as static PMMA-spacers are routinely used in two
      staged septic total knee arthroplasty (TKA) revision surgery. However, if bone
      defects are excessive and there is substantial instability, conventional spacers
      without additional stabilisation are inappropriate. Due to the increasing number
      of multiple revisions and larger bone defects, an absolutely stable spacer
      construct with appropriate fixation in the remaining bone is required. METHODS:
      After TKA removal and debridement, AO external fixator steel rods were inserted
      "press-fit" into the femoral and tibial medullary canal in this technique. Both
      rods were sealed with bone cement (PMMA) and connected at the joint level in 5
      degrees  of flexion by an AO external fixator "tube-to-tube" connector.
      Comparable to a conventional static spacer the joint space is filled with
      individual antibiotic loaded PMMA. The restoration of the leg axis as well as the
      distraction of the joint is crucial to preserve the joint space for the second
      stage TKA reimplantation. Postoperative mobilisation can be conducted under full
      weight-bearing conditions without external orthosis. CONCLUSION: This technique
      allows a safe intramedullary fixation of a modified static spacer in septic TKA
      revision with large bone defects and substantial instability with avoidance of
      common spacer complications and excellent patient mobilisation.

PMID- 25874402
TI  - [How to determine the rotation of the femoral component].
AB  - The different landmarks for determination of the rotation of the femoral
      component are shown and specific pros and cons are discussed. The videos
      demonstrate how to identify them intraoperatively. 

PMID- 25874403
TI  - [Surgical technique: reconstruction of deficient extensor apparatus of the knee -
      a case report].
AB  - Injuries to the extensor apparatus of the knee are a rare but in case of their
      occurrence a serious injury. In the following discussion, the focus is on
      treatment of chronic patellar tendon tears. The aim of surgical treatment is the
      recovery of the active extension and full weight-bearing ability of the leg. The
      video presentation shows the operative treatment of a patient with a chronic
      extensor mechanism deficiency of the knee after multiple revision of a total knee
      arthroplasty due to periprosthetic infection and three-times occurrence of a
      patella tendon tear. A frame-shaped reinforcement between patella and tibial
      tuberosity by FiberTape(r) combined with a medial gastrocnemius flap was
      performed. This type of surgery is indicated in cases of large defects of the
      patellar tendon that cannot be treated with end-to-end suture or simple
      augmentation with autologous tendons (e.g. semitendinosus). In addition to
      augmentation of the tendon defect, cutaneous soft tissue defects around the knee
      and proximal lower leg can be covered. In general, the best treatment option is
      chosen according to size of the defect, the quality of the tendon tissue and
      possible previous surgery on the knee joint. There are no reports of large series
      of chronic patella tendon tears, but only isolated cases using a variety of
      techniques. In addition with low level of evidence, there is currently no
      established gold standard in the surgical treatment of insufficiencies of the
      extensor apparatus of the knee. 

PMID- 25874404
TI  - [Diagnosis and therapy of particle disease in total hip arthroplasty].
AB  - Particle disease is caused by periarticular accumulation of attrition particles
      and the inflammatory reaction of the body's tissue. This process may result in
      osteolysis or soft tissue transformation which presents itself symptomless in the
      beginning and can proceed to aseptic implant loosening, fracture, implant
      breaking as a result of the inappropriate osseous support and to algetic and
      destructive soft tissue reactions as well. Attrition particles originate from
      tribological pairing, and the extent of the attrition or the particle
      concentration depend on different factors as there are the tribological pairing's
      material, the head size, the patient's level of activity, and the implant
      position. Attrition particles can also be found in the range of any modular
      connection. Particle disease and its resulting morphological alterations of the
      tribological pairing is one of the most frequent reasons for re-operation in hip
      endoprosthetics. 

PMID- 25874405
TI  - Prolonged Lung Allograft Ischemia and Posttransplant Outcome.

PMID- 25874406
TI  - Machine learning methods enable predictive modeling of antibody feature:function
      relationships in RV144 vaccinees.
AB  - The adaptive immune response to vaccination or infection can lead to the
      production of specific antibodies to neutralize the pathogen or recruit innate
      immune effector cells for help. The non-neutralizing role of antibodies in
      stimulating effector cell responses may have been a key mechanism of the
      protection observed in the RV144 HIV vaccine trial. In an extensive investigation
      of a rich set of data collected from RV144 vaccine recipients, we here employ
      machine learning methods to identify and model associations between antibody
      features (IgG subclass and antigen specificity) and effector function activities
      (antibody dependent cellular phagocytosis, cellular cytotoxicity, and cytokine
      release). We demonstrate via cross-validation that classification and regression
      approaches can effectively use the antibody features to robustly predict
      qualitative and quantitative functional outcomes. This integration of antibody
      feature and function data within a machine learning framework provides a new,
      objective approach to discovering and assessing multivariate immune correlates. 

PMID- 25874407
TI  - Expertly validated models and phylogenetically-controlled analysis suggests
      responses to climate change are related to species traits in the order
      lagomorpha.
AB  - Climate change during the past five decades has impacted significantly on natural
      ecosystems, and the rate of current climate change is of great concern among
      conservation biologists. Species Distribution Models (SDMs) have been used widely
      to project changes in species' bioclimatic envelopes under future climate
      scenarios. Here, we aimed to advance this technique by assessing future changes
      in the bioclimatic envelopes of an entire mammalian order, the Lagomorpha, using
      a novel framework for model validation based jointly on subjective expert
      evaluation and objective model evaluation statistics. SDMs were built using
      climatic, topographical, and habitat variables for all 87 lagomorph species under
      past and current climate scenarios. Expert evaluation and Kappa values were used
      to validate past and current models and only those deemed 'modellable' within our
      framework were projected under future climate scenarios (58 species).
      Phylogenetically-controlled regressions were used to test whether species traits
      correlated with predicted responses to climate change. Climate change is likely
      to impact more than two-thirds of lagomorph species, with leporids (rabbits,
      hares, and jackrabbits) likely to undertake poleward shifts with little overall
      change in range extent, whilst pikas are likely to show extreme shifts to higher
      altitudes associated with marked range declines, including the likely extinction
      of Kozlov's Pika (Ochotona koslowi). Smaller-bodied species were more likely to
      exhibit range contractions and elevational increases, but showing little poleward
      movement, and fecund species were more likely to shift latitudinally and
      elevationally. Our results suggest that species traits may be important
      indicators of future climate change and we believe multi-species approaches, as
      demonstrated here, are likely to lead to more effective mitigation measures and
      conservation management. We strongly advocate studies minimising data gaps in our
      knowledge of the Order, specifically collecting more specimens for biodiversity
      archives and targeting data deficient geographic regions. 

PMID- 25874408
TI  - Micelle structure in a photoresponsive surfactant with and without solubilized
      ethylbenzene from small-angle neutron scattering.
AB  - Photoresponsive micellar systems of 4-butylazobenzene-4'-
      (oxyethyl)trimethylammonium bromide (AZTMA) were examined with and without
      ethylbenzene using small-angle neutron scattering (SANS). Analysis of SANS
      profiles showed that an aqueous solution containing 5, 10, and 50 mM AZTMA forms
      prolate spheroids with a long radius (Ra) of 38 A and a short radius (Rb) of 21
      A. In the 5 mM AZTMA solution, the concentration of micelles decreased upon UV
      light irradiation, while their size and shape remained almost unchanged.
      Subsequent visible light irradiation reversed the decrease and increased the
      number of micelles. In contrast, 10 and 50 mM AZTMA solutions showed that the
      number and long radius of the micelles decreased with UV light irradiation, while
      subsequent exposure to visible light irradiation restored them. For AZTMA
      micellar solutions equilibrated with excess ethylbenzene, the solubilized amount
      of ethylbenzene increased upon UV light irradiation due to enhanced swelling of
      the micelles with cis-AZTMA. This photoinduced uptake of the solubilizate has
      potential applicability for the collection and removal of hazardous oily
      substances. 

PMID- 25874409
TI  - Of PCOS symptoms, hirsutism has the most significant impact on the quality of
      life of Iranian women.
AB  - INTRODUCTION: Polycystic ovary syndrome is a common endocrine disorder affecting
      women both physically and psychologically and can lead to a poor quality of life
      compared to their normal counterparts. The aim of the present study was to assess
      the impact of various clinical features of polycystic ovary syndrome on the
      health-related quality of life of Iranian women diagnosed with this syndrome.
      MATERIALS AND METHODS: A total of 796 women diagnosed with polycystic ovary
      syndrome, aged 15-49 years, completed the questionnaires, interviews, and medical
      assessments required for this study. A reliable and validated Persian version of
      the health-related quality of life questionnaire for polycystic ovary syndrome
      patients was used. Linear regression models were used to assess the association
      between the symptoms of polycystic ovary syndrome and health-related quality of
      life. RESULTS: The mean age of participants was 28.02 years. 35.4% of the
      subjects were classified as overweight or obese. Hirsutism, was reported to have
      the strongest impact on the patients' health-related quality of life, followed in
      descending order by body mass index, irregular menses and infertility. The
      relative level of hirsutism was directly proportional to decrease in health
      related quality of life score (p<0.001). CONCLUSIONS: The results of the study
      found that hirsutism had the strongest impact on the health-related quality of
      life measures in Iranian women diagnosed with polycystic ovary syndrome. Health
      care officials need to evaluate in depth the effect of each clinical feature of
      polycystic ovary syndrome separately and design management strategies, keeping in
      mind the psychological and physical manifestations.

PMID- 25874410
TI  - Cancer stem cells as therapeutic targets of hepato-biliary-pancreatic cancers.
AB  - Heterogeneity is one of the essential hallmarks of malignancies. Within bulk
      cancer cells, a striking variability differs in biological characteristics
      including the proliferation rate, cell-cell interaction, metastatic tendency and
      even sensitivity to anticancer therapies. Such diversity makes the investigation
      and treatment of the cancers complicated. Increasing evidence suggests this
      plasticity of cancers is a result of self-renewing and differentiation of a small
      subpopulation of cancer cells with stem-like properties, called cancer stem cells
      (CSCs). More importantly, CSCs are believed to be responsible for the resistance
      to conventional therapies and metastatic abilities in clinical practice. This
      review summarizes the molecular pathogenesis of hepato-biliary-pancreatic CSCs on
      the basis of the recent studies, and promising strategy of novel therapy
      targeting the signal transduction pathways or potentially epigenetic addictions
      of CSCs.

PMID- 25874411
TI  - Pertussis prevalence and its determinants among children with persistent cough in
      urban Uganda.
AB  - BACKGROUND: We determined prevalence of pertussis infection and its associated
      host and environmental factors to generate information that would guide
      strategies for disease control. METHODS: In a cross-sectional study, 449 children
      aged 3 months to 12 years with persistent cough lasting >=14 days were enrolled
      and evaluated for pertussis using DNA polymerase chain reaction (PCR) and ELISA
      serology tests. RESULTS: Pertussis prevalence was 67 (15% (95% Confidence
      Interval (CI): 12-18)) and 81 (20% (95% CI: 16-24)) by PCR and ELISA,
      respectively among 449 participating children. The prevalence was highest in
      children with >59 months of age despite high vaccination coverage of 94% in this
      age group. Study demographic and clinical characteristics were similar between
      pertussis and non-pertussis cases. Of the 449 children, 133 (30%) had a coughing
      household member and 316 (70%) did not. Among 133 children that had a coughing
      household member, sex of child, sharing bed with a coughing household member and
      having a coughing individual in the neighborhood were factors associated with
      pertussis. Children that had shared a bed with a coughing household individual
      had seven-fold likelihood of having pertussis compared to children that did not
      (odds ratio (OR) 7.16 (95% CI: 1.24-41.44)). Among the 316 children that did not
      have a coughing household member, age <23 months, having or contact with a
      coughing individual in neighborhood, a residence with one room, and having a
      caretaker with >40 years of age were the factors associated with pertussis. Age
      <23months was three times more likely to be associated with pertussis compared to
      age 24-59 months (OR 2.97 (95% CI: 1.07-8.28)). CONCLUSION: Findings suggest high
      prevalence of pertussis among children with persistent cough at a health facility
      and it was marked in children >59 months of age, suggesting the possibility of
      waning immunity. The factors associated with pertussis varied by presence or
      absence of a coughing household member.

PMID- 25874412
TI  - Distribution and fate of synthetic musks in the Songhua River, Northeastern
      China: influence of environmental variables.
AB  - Contamination levels and spatial and temporal distributions of six typical
      synthetic musks (SMs) in water and sediment of the Songhua River in Northeastern
      China were investigated. Experimental data for 72 water and 52 sediment samples
      collected at 29 sampling sites over 12 months spanning 2011-2012 showed that the
      Songhua River had been contaminated to different degrees at various sites
      separately from the river's source. The polycyclic musks 1,3,4,6,7,8-hexahydro
      4,6,6,7,8,8-hexamethylcyclopenta-(g)-2-benzopyran (HHCB) (Galaxolide) and 7
      acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene (AHTN) (Tonalide)
      were found most frequently and at the highest levels. Concentrations of HHCB were
      <2-37 ng/L in water and <0.5-17.5 ng/g dry weight (dw) in sediment. AHTN was <1-8
      ng/L in water and <0.5-5.7 ng/g dw in sediment. Statistical relationships between
      SM concentrations and four environmental variables (temperature, illumination,
      runoff, and population density) in the Songhua River Basin were formulated.
      Concentration levels varied proportionately with the size of the city along the
      river, while the distribution patterns showed clear seasonal variations.
      HHCB/AHTN ratios mirrored the transfer and transmitting process of SMs.
      Concentrations of target compounds were correlated with each other, suggesting
      similar exposure sources. Environmental risk assessment of SMs presented seasonal
      variations and provided baseline information on SM exposure in the Songhua River
      Basin.

PMID- 25874413
TI  - Effects of ultrasonic-assisted thermophilic bacteria pretreatment on hydrolysis,
      acidification, and microbial communities in waste-activated sludge fermentation
      process.
AB  - A novel pretreatment method combining ultrasonic with thermophilic bacteria
      (Geobacillus sp. G1) was employed to pretreat waste-activated sludge (WAS) for
      enhancing the WAS hydrolysis and subsequent volatile fatty acids (VFAs)
      production. The soluble protein and carbohydrate were mostly released from
      intracellular ultrasonic-assisted Geobacillus sp. G1 pretreatment, and
      accumulated to 917 +/- 70 and 772 +/- 89 mg COD/L, respectively, which were 2.53-
      and 2.62-fold higher than that obtained in control test. Excitation emission
      matrix (EEM) fluorescence spectroscopy revealed the highest fluorescence
      intensity (FI) of protein-like substances, indicating the synergistic effect of
      ultrasonic and Geobacillus sp. G1 pretreatments on WAS hydrolysis. The maximum
      VFAs accumulation was 4437 +/- 15 mg COD/L obtained in ultrasonic-assisted
      Geobacillus sp. G1 pretreatment test. High-throughput pyrosequencing analysis
      investigated that the microbial communities were substantial determined by the
      pretreatment used. The hydrolysis enhancement was caused by an increase in
      extracellular enzymes, which was produced by one of dominant species Caloramator
      sp. The positive effect was well explained to the enhancement of WAS hydrolysis
      and final VFAs accumulation.

PMID- 25874414
TI  - Adsorption/desorption and bioavailability of methamphetamine in simulated
      gastrointestinal fluids under the presence of multiwalled carbon nanotubes.
AB  - Adsorption/desorption and desorption hysteresis of methamphetamine (MMA) on
      carbon nanotubes (CNTs) as well as bioavailability of MMA were studied in
      simulated gastrointestinal fluids and background fluids. Adsorption of MMA in
      near-neutral (weak alkaline) intestinal fluid was enhanced, while adsorption of
      MMA on CNTs in acid gastric fluid was suppressed. Desorption of MMA is divided
      into fast and slow stages, and fast desorption conducting in the gastric fluid
      lasted shortly and slow desorption occurred in intestinal fluid; pepsin can
      enhance the release of MMA in gastrointestinal system. While, the acidic
      condition in gastric fluid is the main factor which causes the release of MMA.
      The amount of MMA released from CNTs in different fluids follows the order
      gastric > background (pH = 2.0) > intestinal (fed) > intestinal (fasted) >
      background (pH = 7.5). These findings in the simulated gastrointestinal system
      suggest that the release of MMA from CNTs could be promoted by biomacromolecules
      (such as pepsin and bile salts in digestive tract); thus, the bioavailability of
      MMA is enhanced.

PMID- 25874415
TI  - Evaluation of phytotoxicity effect of olive mill wastewater treated by different
      technologies on seed germination of barley (Hordeum vulgare L.).
AB  - Olive-mill wastewater (OMW) is a by-product effluent of olive oil extraction
      process that is produced in large amount in the Mediterranean region. OMW is
      believed to induce phytotoxic effect on organisms including seed germination and
      plant growth. The objective of this study was to evaluate the impact of untreated
      and treated OMW with different techniques on seed germination of barley (Hordeum
      vulgare L.). The following treatments were investigated: (1) tap water (control);
      (2) OMW treated by aerobic biological technology in a Jacto Reactor (JR); (3) OMW
      treated by solar fenton oxidation (SFO); (4) OMW treated by microfiltration
      followed by nanofiltration (MF+NF); (5) OMW treated by microfiltration followed
      by reverse osmosis (MF+RO) process; (6) diluted OMW with tap water (25 % OMW);
      (7) diluted OMW with tap water (50 % OMW); (8) diluted OMW with tap water (75 %
      OMW); and (9) untreated OMW (100 % OMW). A germination test was conducted in an
      incubator at temperature of 23 (?)C. In each petri dish, a filter paper was
      mounted and ten seeds of barley were placed on the filter paper. Five milliliter
      of water were added to each petri dish. The seed germination was determined by
      counting the number of germinated seeds to calculate the percentage of
      germination (G %). Germination rate index (GRI), seed vigor index (SVI), and
      phytotoxicity index (PI) were also calculated. Then, the dry weights and lengths
      of the shoots and the roots of the germinated seeds were measured. The results
      show that 100, 75, and 50 %OMW were very phytotoxic and completely prohibited
      seed germination. However, phytotoxicity decreased significantly following
      treatments of OMW with all techniques investigated and by the 25 % OMW dilution,
      as results of removing the phenols and other phytotoxic organic compounds from
      the OMW or by diluting it. This was evidenced by relative enhancement of the dry
      weights and lengths of shoot and root as well as the G %, GRI, SVG, and PI. It
      was concluded that if OMW will be used for irrigating crops, it has to be first
      treated or diluted with tap water at a ratio of 1:3 OMW:water at least. The most
      efficient treatment techniques in reducing the phytotoxicity of OMW were the
      MF+RO, followed by SFO and JR.

PMID- 25874416
TI  - Modeling of leachate recirculation using vertical wells in bioreactor landfills.
AB  - Leachate recirculation (LR) in municipal solid waste (MSW) landfills operated as
      bioreactors offers significant economic and environmental benefits. The
      subsurface application method of vertical wells is one of the most common LR
      techniques. The objective of this study was to develop a novel two-dimensional
      model of leachate recirculation using vertical wells. This novel method can
      describe leachate flow considering the effects of MSW settlement while also
      accounting separately for leachate flow in saturated and unsaturated zones. In
      this paper, a settlement model for MSW when considering the effects of
      compression and biodegradation on the MSW porosity was adopted. A numerical model
      was proposed using new governing equations for the saturated and unsaturated
      zones of a landfill. The following design parameters were evaluated by simulating
      the recirculated leachate volume and the influence zones of waste under steady
      state flow conditions: (1) the effect of MSW settlement, (2) the effect of the
      initial void ratio, (3) the effect of the injected head, (4) the effect of the
      unit weight, (5) the effect of the biodegradation rate, and (6) the effect of the
      compression coefficient. The influence zones of LR when considering the effect of
      MSW settlement are smaller than those when neglecting the effect. The influence
      zones and LR volume increased with an increase in the injection pressure head and
      initial void ratio of MSW. The proposed method and the calculation results can
      provide important insight into the hydrological behavior of bioreactor landfills.

PMID- 25874417
TI  - Effects of prolonged consumption of water with elevated nitrate levels on certain
      metabolic parameters of dairy cattle and use of clinoptilolite for their
      amelioration.
AB  - Elevated levels of nitrates in feed and water can pose a significant risk for
      dairy cattle, due to their cumulative action. The effect of prolonged consumption
      of water naturally contaminated with nitrates on some metabolic parameters in
      dairy cows was investigated at the present study. Concurrently, whether in-feed
      inclusion of clinoptilolite, a natural zeolite with high selectivity for ammonia
      cations, could ameliorate nitrate consumption consequences was examined. Two
      experiments were run simultaneously in two farms each. In both, farms were
      assigned into two groups according to nitrate levels in borehole water (NG > 40
      ppm; CG < 40 ppm). Furthermore, in experiment 2, the incorporation of
      clinoptilolite in the ration was taken into account (NC-clinoptilolite feeding;
      CNC-controls). In experiment 1, blood urea nitrogen (BUN) and beta
      hydroxybutyrate (BHBA) concentrations appeared to be affected by nitrate
      consumption and were significantly higher in NG animals. In experiment 2, BUN
      concentration was significantly lower in the NC group. The prolonged consumption
      of water with increased nitrate levels seemed, to some degree, to impair protein
      metabolism and glucose utilization, while the dietary administration of
      clinoptilolite could alleviate the nitrates' effects.

PMID- 25874419
TI  - Do concentrations of pharmaceuticals in sewage reflect prescription figures?
AB  - In recent years, it has been demonstrated that sewage-based epidemiology can
      deliver interesting information on trends in illicit drug consumption. However,
      until now, no real evidence exists that the measured concentrations of drugs in
      sewage can be exactly correlated with the amounts of drugs used by a specific
      population. This study aimed therefore at correlating detailed monthly
      prescription figures of 11 pharmaceuticals (atenolol, bisoprolol, citalopram,
      fluoxetine, venlafaxine, losartan, telmisartan, valsartan, carbamazepine,
      metformin, and tramadol) with measured concentrations of these compounds in
      influent sewage from five sewage treatment plants in Belgium. For 7 out of the 11
      substances, a ratio between loads calculated from the prescription figures and
      loads calculated from measured concentrations in the range of 0.30-3.00 was
      observed. For four pharmaceuticals (atenolol, bisoprolol, telmisartan, and
      venlafaxine), the observed relationship was less pronounced. The manuscript gives
      an overview of the possible uncertainties that are related with the calculated
      correlations. This study highlights the need for gathering all the necessary
      information regarding sewage sampling, stability of substances in sewage,
      pharmacokinetics, and analytical method performance when sewage-based
      epidemiology studies are performed. 

PMID- 25874418
TI  - Spatial distribution, health risk assessment and statistical source
      identification of the trace elements in surface water from the Xiangjiang River,
      China.
AB  - Surface water samples were collected from the sampling sites throughout the
      Xiangjiang River for investigating spatial variation, risk assessment and source
      identification of the trace elements. The results indicated that the mean
      concentrations of the elements were under the permissible limits as prescribed by
      guidelines except arsenic (As). Based on the health risk indexes, the primary
      contributor to the chronic risks was arsenic (As), which was suggested to be the
      most important pollutant leading to non-carcinogenic and carcinogenic concerns.
      Individuals, who depend on surface water from the Xiangjiang River for potable
      and domestic use, might be subjected to the integrated health risks for exposure
      to the mixed trace elements. Children were more sensitive to the risks than the
      adults, and the oral intake was the primary exposure pathway. Besides,
      multivariate statistical analyses revealed that arsenic (As), cadmium (Cd), lead
      (Pb), selenium (Se), and mercury (Hg) mainly derived from the chemical industrial
      wastewaters and the coal burning, and zinc (Zn) copper (Cu) and chromium (Cr)
      mainly originated from the natural erosion, the mineral exploitation activities,
      and the non-point agricultural sources. As a whole, the upstream of the
      Xiangjiang River was explained as the high polluted region relatively. 

PMID- 25874420
TI  - Modification of bentonite with cationic surfactant for the enhanced retention of
      bisphenol A from landfill leachate.
AB  - Bentonite was modified with cationic surfactant hexadecyl trimethyl ammonium
      bromide (HTAB) as landfill liner to retard the transportation of bisphenol A
      (BPA) for the first time. The modification was confirmed to form a lateral bi
      layer in the interlayer space of bentonite by scanning electron microscope, X-ray
      diffraction, and Fourier transform infrared spectroscopy. The introduction of
      HTAB into the internal position of bentonite led to an increased interlayer space
      of bentonite from 15.0 to 20.9 A and a higher sorption affinity for BPA (10.449
      mg/g of HTAB-bentonite and 3.413 mg/g of raw bentonite). According to the
      Freundlich model, the maximum adsorption capacity of the HTAB-bentonite was found
      to be 0.410 mg/g. The sorption capacity of raw bentonite and HTAB-bentonite both
      decreased at alkaline conditions. Although the hydraulic conductivity of HTAB
      bentonite was higher than that of raw bentonite, results of laboratory
      permeability and column tests indicated that HTAB-bentonite obviously extended
      the BPA breakthrough time by 43.4 %. The properties of the HTAB-bentonite
      revealed its notable advantages as components of landfill liners material to
      retain BPA in leachate. 

PMID- 25874421
TI  - Responses of tall fescue (Festuca arundinacea) to growth in naphthalene
      contaminated sand: xenobiotic stress versus water stress.
AB  - The adaptations of tall fescue (Festuca arundinacea) arising from growth in
      naphthalene-contaminated sand (0.8 g kg(-1) sand dry weight (dw)) were
      investigated in the contexts of xenobiotic stress and water stress. The transfer
      of polycyclic aromatic hydrocarbons (PAHs) across the root endodermis was
      investigated using the hydrophobic Nile red stain as a PAH homologue. Nile red
      was applied to the epidermis of a living root to visualise uptake into the root
      through the transpiration stream, and the distance travelled by the stain into
      the root tissues was investigated using epi-fluorescence microscopy (Nikon
      Eclipse 90i). The results showed that the Nile red applied to the roots grown in
      naphthalene-contaminated sand was unable to penetrate the roots beyond the
      endodermis, whereas those grown in 'clean' sand showed evidence of uptake into
      the xylem vessels beyond the endodermis. Furthermore, partial collapse was
      observed in the cortex of naphthalene-treated roots, suggesting drought stress.
      Interestingly, the treated plants showed visual resilience to drought stress
      whilst the leaves of the control plants showed signs of wilting.

PMID- 25874422
TI  - Association of bisphenol A exposure with overweight in the elderly: a panel
      study.
AB  - Bisphenol A (BPA) is an ubiquitous chemical, which is an endocrine disruptor.
      Recent epidemiological studies have suggested a relationship between BPA exposure
      and body weight. However, most of these studies were cross-sectional and not on
      elderly people. We conducted a panel study with repeated measurements to evaluate
      the relationship between BPA and overweight in elderly people. A total of 560
      elderly participants aged >=60 years were recruited in Seoul from 2008 to 2010.
      Urinary BPA levels and body mass index (BMI, kg/m(2)) were measured at every
      visit. We defined a BMI >=25 as overweight and examined the relations between
      urinary BPA and BMI or overweight. Repeated measures analysis was performed after
      adjusting for age, sex, low-density lipoprotein cholesterol levels, alcohol
      consumption, regular exercise, total calorie intake, fatty acid intake, urinary
      cotinine levels, and the status of diabetes mellitus. The geometric mean of BPA
      was 0.67 MUg/g creatinine. The odds ratio (OR) of overweight was 1.17 (95 %
      confidence interval [CI] 1.04-1.32) per interquartile range increase of log
      transformed BPA. When stratified based on sex, we observed a significant
      association in women (OR 1.25; 95 % CI 1.09-1.45) but not in men (OR 0.97; 95 %
      CI 0.77-1.22). The ORs of overweight increased with quartiles of BPA in women
      (quartile 2 vs 1: OR 1.54; 95 % CI 1.02-2.32, 3 vs 1: OR 1.70; 95 % CI 1.10-2.62,
      and 4 vs 1: OR 1.81; 95 % CI 1.13-2.92). Our results suggest that urinary BPA
      levels are significantly associated with overweight in elderly women but not
      elderly men.

PMID- 25874423
TI  - Inverted U-shape relationships of the weather as biometeorological and hospital
      admissions due to carcinoma in situ and benign neoplasm in Germany in 2009-2011.
AB  - We aimed to understand the relationships of the weather as biometeorological and
      hospital admissions due to carcinoma in situ and benign neoplasms, which have
      been less paid attention to, in a national setting in recent years. This is an
      ecological study. Ten percent of daily hospital admissions from the included
      hospitals (n = 1618) across Germany that were available between 1 January, 2009
      and 31 December, 2011 (n = 5,235,600) were extracted from Statistisches
      Bundesamt, Germany. We identified D00-D48 in situ neoplasms, benign neoplasms and
      neoplasms of uncertain or unknown behaviour by International Classification of
      Diseases version 10 as the study outcomes. Daily weather data from 64 weather
      stations that covered 13 German states including air temperature, humidity, wind
      speed, cloud cover, radiation flux and vapour pressure were obtained and
      generated into physiologically equivalent temperature (PET). For most subtypes,
      peaks of admissions were observed in spring and late autumn. There could be four
      groups of phenomenon among these admissions. To be specific, D06, D16, D21, D24
      25, D35 and D39 peaked when PET was at 0  degrees C. D46 peaked when PET was at 5
      10  degrees C. D03, D04 and D33 had linear relationships. Other admissions peaked
      when PET was between 0 and 5  degrees C. All admissions were in common with a
      drop when PET reached 10  degrees C or higher. More medical resources could have
      been needed on days when PETs were at 0-10  degrees C than on other days.
      Adaptation to such weather change for medical professionals and the general
      public would seem to be imperative.

PMID- 25874424
TI  - Endolithic microbial communities in carbonate precipitates from serpentinite
      hosted hyperalkaline springs of the Voltri Massif (Ligurian Alps, Northern
      Italy).
AB  - The Voltri Massif is an ophiolitic complex located in the Ligurian Alps close to
      the city of Genova (Northern Italy) where several springs discharge high pH (up
      to 11.7), low salinity waters produced by the active serpentinization of the
      ultramafic basement. Mixing of these hyperalkaline waters with the river waters
      along with the uptake of atmospheric carbon dioxide forms brownish carbonate
      precipitates covering the bedrock at the springs. Diverse archaeal and bacterial
      communities were detected in these carbonate precipitates using 454
      pyrosequencing analyses of 16S ribosomal RNA (rRNA) genes. Archaeal communities
      were dominated by members of potential methane-producing and/or methane-oxidizing
      Methanobacteriales and Methanosarcinales (Euryarchaeota) together with ammonia
      oxidizing Nitrososphaerales (Thaumarchaeota) similar to those found in other
      serpentinization-driven submarine and terrestrial ecosystems. Bacterial
      communities consisted of members of the Proteobacteria, Actinobacteria,
      Planctomycetes, Bacteroidetes, Chloroflexi, and Verrucomicrobia phyla, altogether
      accounting for 92.2% of total retrieved bacterial 16S rRNA gene sequences.
      Amongst Bacteria, potential chemolithotrophy was mainly associated with Alpha-
      and Betaproteobacteria classes, including nitrogen-fixing, methane-oxidizing or
      hydrogen-oxidizing representatives of the genera Azospirillum, Methylosinus, and
      Hydrogenophaga/'Serpentinomonas', respectively. Besides, potential
      chemoorganotrophy was attributed mainly to representatives of Actinobacteria and
      Planctomycetales phyla. The reported 16S rRNA gene data strongly suggested that
      hydrogen, methane, and nitrogen-based chemolithotrophy can sustain growth of the
      microbial communities inhabiting the carbonate precipitates in the hyperalkaline
      springs of the Voltri Massif, similarly to what was previously observed in other
      serpentinite-hosted ecosystems.

PMID- 25874425
TI  - Contamination of nitrate in groundwater and its potential human health: a case
      study of lower Mae Klong river basin, Thailand.
AB  - Nitrate contamination in groundwater is a worldwide problem especially in
      agricultural countries. Environmental factors, such as land-use pattern, type of
      aquifer, and soil-drainage capacity, affect the level of contamination. Exposure
      to high levels of nitrate in groundwater may contribute to adverse health effects
      among residents who use groundwater for consumption. This study aimed to
      determine the relationship between nitrate levels in groundwater with land-use
      pattern, type of aquifer, and soil-drainage capacity, in Photharam District,
      Ratchaburi Province, lower Mae Klong basin, Thailand. Health risk maps were
      created based on hazard quotient to quantify the potential health risk of the
      residents using US Environmental Protection Agency (U.S. EPA) health risk
      assessment model. The results showed the influence of land-use patterns, type of
      aquifer, and soil-drainage capacity on nitrate contamination. It was found that
      most of the residents in the studied area were not at risk; however, a
      groundwater nitrate monitoring system should be implemented. 

PMID- 25874426
TI  - Cd accumulation and subcellular distribution in two ecotypes of Kyllinga
      brevifolia Rottb as affected by Cd treatments.
AB  - The Cadmium (Cd) accumulation capacity and subcellular distribution in the mining
      ecotype (ME) and non-mining ecotype (NME) of Kyllinga brevifolia Rottb were
      investigated in pot experiments. The results showed that average Cd contents in
      shoots of the two ecotypes of K. brevifolia were higher than those in roots,
      whereas Cd concentrations in roots were greater than those in shoots. Also, shoot
      Cd contents in NME of K. brevifolia were 1.65-45.45 times greater than those in
      ME when the plants were grown at 5, 25, 50, and 100 mg Cd kg(-1) soil. Moreover,
      Cd contents in the roots in NME were 1.75-45.45 times higher than those in ME.
      Subcellular distribution of Cd demonstrated that the majority of Cd in the two
      ecotypes of K. brevifolia was distributed in the cell walls and soluble fraction,
      and a small percentage of Cd existed in organelle fraction. In addition,
      proportions of Cd distributed in shoots and roots cell walls of NME were greater
      than those in ME. It could be assumed that compared with ME, NME of K. brevifolia
      has better Cd accumulation capacity, and the subcellular distribution of Cd might
      be one of the mechanisms to explain such phenomena.

PMID- 25874427
TI  - Occurrence and potential risk of currently used pesticides in sediments of the
      Alqueva reservoir (Guadiana Basin).
AB  - The evaluation of sediments, concerning to pesticides, constitutes an important
      step for the understanding of the principal sources of contamination of the
      surface water. Hence, the purpose of this study was to evaluate for the first
      time the occurrence, distribution and risk of pesticides in sediments of the
      Alqueva reservoir, the largest reservoir in the Europe. For this purpose, the
      occurrence of 22 pesticides and some of their degradation products was determined
      in surficial sediments of the Alqueva reservoir. To assess the potential risk on
      ecosystem, the measured concentrations of pesticides were compared with
      regulatory and toxicological benchmarks. Of the 22 pesticides analysed, only 8
      were detected. Diuron was the pesticide detected in greater concentration,
      followed by terbuthylazine and chlortoluron. The sediments most polluted by
      pesticides were from Lucefecit, constituted totally by fine particles (<0.063 mm)
      and with high values of organic matter, and are located nearby large agricultural
      fields. The risk assessment allowed us to conclude that the sediments from the
      Alqueva reservoir presented low risk, concerning to pesticides, for the various
      communities that integrate the aquatic ecosystems. However, some of the compounds
      detected present a high potential for bioaccumulation that may lead to their
      bioamplification in the trophic chain, reaching concentrations higher than their
      acceptable daily intake, putting, in this way the populations at risk. 

PMID- 25874428
TI  - Phthalate esters contamination in soils and vegetables of plastic film
      greenhouses of suburb Nanjing, China and the potential human health risk.
AB  - The contamination of phthalate esters (PAEs) has become a potential threat to the
      environment and human health because they could be easily released as
      plasticizers from the daily supply products, especially in polyethylene films.
      Concentration levels of total six PAEs, nominated as priority pollutants by the
      US Environmental Protection Agency (USEPA), were investigated in soils and
      vegetables from four greenhouse areas in suburbs of Nanjing, East China. Total
      PAEs concentration ranged from 930 +/- 840 to 2,450 +/- 710 MUg kg(-1) (dry
      weight (DW)) in soil and from 790 +/- 630 to 3,010 +/- 2,130 MUg kg(-1) in
      vegetables. Higher concentrations of PAEs were found in soils except in Suo Shi
      (SS) area and in vegetables, especially in potherb mustard and purple tsai-tai
      samples. Risk assessment mainly based on the exposures of soil ingestion and
      daily vegetable intake indicated that bis(2-ethylhexyl) phthalate (DEHP) in the
      samples from Gu Li (GL) and Hu Shu (HS) exhibited the highest hazard to children
      less than 6-year old. Therefore, the human health risk of the PAEs contamination
      in soils and vegetables should greatly be of a concern, especially for their
      environmental estrogen analog effects.

PMID- 25874429
TI  - Oil in the Gulf of Mexico after the capping of the BP/Deepwater Horizon
      Mississippi Canyon (MC-252) well.
AB  - Evidence of fresh oil from the BP/Deepwater Horizon Mississippi Canyon-252 (MC
      252) well was found in the northern Gulf of Mexico up to 1 year and 10 months
      after it was capped on 15 July 2010. Offshore and coastal samples collected after
      capping displayed ratios of biomarkers matching those of MC-252 crude oil. Pre-
      and post-capping samples were compared. Little weathering had occurred, based on
      the abundance of low-molecular-weight (LMW) n-alkanes and polycyclic aromatic
      hydrocarbons (PAHs) in the post-capping samples. The occurrence of fresh oil in
      offshore waters and coastal areas suggest that the MC-252 well continued to leak
      hydrocarbons into the Gulf of Mexico at least until 22 May 2012, the end of this
      study period.

PMID- 25874430
TI  - Bioaccumulative characteristics of tetrabromobisphenol A and
      hexabromocyclododecanes in multi-tissues of prey and predator fish from an e
      waste site, South China.
AB  - Tetrabromobisphenol A (TBBPA) and hexabromocyclododecanes (HBCDs) were analyzed
      in 12 tissues of prey (mud carp) and predator (northern snakehead) fish from an e
      waste area, South China. The TBBPA concentrations in different tissues ranged
      from 0.03 to 2.85 ng/g wet weight (ww) in mud carp and 0.04 to 1.30 ng/g ww in
      northern snakehead. The concentrations of HBCDs ranged from 0.07 to 96.9 ng/g ww
      in mud carp and 0.18 to 240 ng/g ww in northern snakehead. HBCD levels in tissues
      were correlated with lipid content for both fish species, while this correlation
      was only found in mud carp for TBBPA. Meanwhile, northern snakehead exhibited
      higher HBCD levels but lower TBBPA levels than mud carps. These observations are
      attributed to the more polar and reactive properties of TBBPA than HBCDs. alpha
      HBCD was the predominant diastereoisomer of HBCDs in all tissues of mud carp and
      northern snakehead, except for chyme of mud carp. All the analyzed tissues in mud
      carp showed an enrichment of (+)-alpha-HBCD enantiomer with EF (enantiomeric
      fraction) values of 0.53-0.62, but that in northern snakehead showed an
      enrichment of (-)-alpha-HBCD enantiomer with EF values of 0.35-0.5. Considering
      the fact that the mud carp is one of the diet items of northern snakehead, the
      different enantiomer accumulation characteristics of alpha-HBCD between the two
      fish species in the present study indicated that prey and predator fish could
      prefer to biotransform different enantiomers of alpha-HBCD.

PMID- 25874431
TI  - Identification of refined petroleum products in contaminated soils using an
      identification index for GC chromatograms.
AB  - Hydrocarbons found in the environment are typically characterized by gas
      chromatography (GC). The shape of the GC chromatogram has been used to identify
      the source of petroleum contamination. However, the conventional practice of
      simply comparing the peak patterns of source products to those of environmental
      samples is dependent on the subjective decisions of individual analysts. We have
      developed and verified a quantitative analytical method for interpreting GC
      chromatograms to distinguish refined petroleum products in contaminated soils. We
      found that chromatograms for gasoline, kerosene, and diesel could be divided into
      three ranges with boundaries at C6, C8, C16, and C26. In addition, the relative
      peak area (RPA(GC)) of each range, a dimensionless ratio of the peak area within
      each range to that of the total range (C6-C26), had a unique value for each
      petroleum product. An identification index for GC chromatograms (ID(GC)), defined
      as the ratio of RPA(GC) of C8-C16 to that of C16-C26, was able to identify diesel
      and kerosene sources in samples extracted from artificially contaminated soils
      even after weathering. Thus, the ID(GC) can be used to effectively distinguish
      between refined petroleum products in contaminated soils.

PMID- 25874432
TI  - Remediation of PAH-contaminated soil at a gas manufacturing plant by a combined
      two-phase partition system washing and microbial degradation process.
AB  - The aim of this study was to design a remediation technique using both soil
      washing and microbial degradation to remove polycyclic aromatic hydrocarbons
      (PAHs) from contaminated soil. PAH biodegradation by inoculation of Mycobacterium
      sp. was first tested. The effectiveness of washing agents (Tween 80 solution,
      biodiesel, and a two-phase partition system (TPPS)) was then evaluated with
      column experiments. Third, the combination of TPPS washing and microbial
      degradation was studied. PAH bioavailability before and after biodegradation and
      the joint remediation was also assessed using hydroxypropyl-beta-cyclodextrin
      (HPCD) extraction. Only phenanthrene and anthracene were noticeably biodegradable
      when the soil was inoculated with Mycobacterium sp. TPPS containing 2% (v/v)
      biodiesel and 2.5% (w/v) Tween 80 was used as the washing agent for the joint
      remediation test because it gave higher PAH extractions than Tween 80 solution
      with lower doses, and there was less residue in the soil. Joint TPPS washing and
      microbial degradation gave a total PAH removal of 92.6%, which was much higher
      than the results from either the biodegradation or washing experiments alone.
      Removals of all high molecular weight (HMW) PAHs were improved. Bioavailable
      concentrations of all PAHs decreased significantly after the joint remediation
      process, indicating that there were reduced risks from all PAHs. The results
      demonstrate that the combination of TPPS washing and microbial degradation is a
      useful and innovative process for remediation of PAH-contaminated soils.

PMID- 25874433
TI  - Preparation and characterization of humic acid-carbon hybrid materials as
      adsorbents for organic micro-pollutants.
AB  - The present work involves the preparation of novel adsorbent materials by the
      insolubilization and hybridization of humic acid (HA) with carbon. The prepared
      materials were characterized by N2 adsorption, elemental analysis, Fourier
      transform infrared spectroscopy, scanning electron microscopy, transmission
      electron microscopy, solid-state (13)C cross polarization magic angle spinning
      nuclear magnetic resonance, and low-field nuclear magnetic resonance (NMR)
      relaxometry on wetted samples. The water solubility of these materials and the
      lack of effect of oxidants were also confirmed. With this background, the
      adsorption capacities toward phenol, 2,4,6-tricholrophenol, and atrazine were
      evaluated, using these as model compounds for organic micropollutants of concern
      in water. Experimental results show that the prepared materials are mesoporous
      and have a higher surface area than humic acid and even than the porous carbon in
      the case of carbon coating. They retain the basic features of the starting
      materials with lowered functional group content. Moreover, there are interesting
      new features. NMR relaxometry shows that equilibration of water uptake is very
      fast, making use in water simple. They have higher adsorption capacities than the
      pure materials, and they can be applied under a wide range of environmental
      conditions. 

PMID- 25874434
TI  - Phytoremediation using microbially mediated metal accumulation in Sorghum
      bicolor.
AB  - Reclaiming land that has been anthropogenically contaminated with multiple heavy
      metal elements, e.g., during mining operations, is a growing challenge worldwide.
      The use of phytoremediation has been discussed with varying success. Here, we
      show that a careful examination of options of microbial determination of plant
      performance is a key element in providing a multielement remediation option for
      such landscapes. We used both (a) mycorrhiza with Rhizophagus irregularis and (b)
      bacterial amendments with Streptomyces acidiscabies E13 and Streptomyces tendae
      F4 to mediate plant-promoting and metal-accumulating properties to Sorghum
      bicolor. In pot experiments, the effects on plant growth and metal uptake were
      scored, and in a field trial at a former uranium leaching heap site near
      Ronneburg, Germany, we could show the efficacy under field conditions. Different
      metals could be extracted at the same time, with varying microbial inoculation
      and soil amendment scenarios possible when a certain metal is the focus of
      interest. Especially, manganese was extracted at very high levels which might be
      useful even for phytomining approaches. 

PMID- 25874435
TI  - Molecular characterization of microbial communities and quantification of
      Mycobacterium immunogenum in metal removal fluids and their associated biofilms.
AB  - A number of human health effects have been associated with exposure to metal
      removal fluids (MRFs). Multiple lines of research suggest that a newly identified
      organism, Mycobacterium immunogenum (MI), appears to have an etiologic role in
      hypersensitivity pneumonitis (HP) in case of MRFs exposed workers. However, our
      knowledge of this organism, other possible causative agents (e.g., Pseudomonads),
      and the microbial ecology of MRFs in general, is limited. In this study, culture
      based methods and small subunit ribosomal RNA gene clone library approach were
      used to characterize microbial communities in MRF bulk fluid and associated
      biofilm samples collected from fluid systems in an automobile engine plant. PCR
      amplification data using universal primers indicate that all samples had
      bacterial and fungal contaminated. Five among 15 samples formed colonies on the
      Mycobacteria agar 7H9 suggesting the likely presence of Mycobacteria in these
      five samples. This observation was confirmed with PCR amplification of 16S rRNA
      gene fragment using Mycobacteria specific primers. Two additional samples,
      Biofilm-1 and Biofilm-3, were positive in PCR amplification for Mycobacteria, yet
      no colonies formed on the 7H9 cultivation agar plates. Real-time PCR was used to
      quantify the abundance of M. immunogenum in these samples, and the data showed
      that the copies of M. immunogenum 16S rRNA gene in the samples ranges from 4.33 *
      10(4) copy/ml to 4.61 * 10(7) copy/ml. Clone library analysis revealed that
      Paecilomyces sp. and Acremonium sp. and Acremonium-like were dominant fungi in
      MRF samples. Various bacterial species from the major phylum of proteobacteria
      were found and Pseudomonas is the dominant bacterial genus in these samples.
      Mycobacteria (more specifically MI) were found in all biofilm samples, including
      biofilms collected from inside the MRF systems and from adjacent environmental
      surfaces, suggesting that biofilms may play an important role in microbial
      ecology in MRFs. Biofilms may provide a shield or sheltered microenvironment for
      the growth and/or colonization of Mycobacteria in MRFs.

PMID- 25874436
TI  - Natural radioactivity in tap waters from the private wells in the surroundings of
      the former Zirovski Vrh uranium mine and the age-dependent dose assessment.
AB  - Activity concentration of (238)U, (234)U, (226)Ra, (228)Ra, (210)Pb and (210)Po
      in tap water from selected springs and private wells in the area of the former
      uranium mine at Zirovski Vrh were determined. A total of 22 tap water samples
      were collected at consumer's houses. The results show that the activity
      concentrations of uranium in water samples are in range (0.17-372) and (0.22-362)
      mBq L(-1) for (238)U and (234)U, respectively. Radium activity concentrations are
      in range (0.14-16.7) and (0.9-11.7) mBq L(-1) for (226)Ra and (228)Ra,
      respectively. (210)Po activity concentration is in range (0.28-8.0) mBq L(-1) and
      can be regarded as the lowest amongst all analysed radionuclides. The range for
      (210)Pb is (0.5-24.6) mBq L(-1). Based on the results obtained for activity
      concentrations of six radionuclides, the committed effective dose for three
      different age groups of population were estimated. It was found that the
      committed effective dose was well below the recommended value of 100 MUSv year(
      1), ranging from 2.3 to 34.3 MUSv year(-1) for adults, from 3.5 to 32.0 MUSv
      year(-1) for children (7-12 years) and from 3.0 to 23.3 MUSv year(-1) for
      infants.

PMID- 25874437
TI  - The dynamic interaction between combustible renewables and waste consumption and
      international tourism: the case of Tunisia.
AB  - This paper employs the autoregressive distributed lag (ARDL) bounds
      methodological approach to investigate the relationship between economic growth,
      combustible renewables and waste consumption, carbon dioxide (CO2) emissions, and
      international tourism for the case of Tunisia spanning the period 1990-2010. The
      results from the Fisher statistic of both the Wald test and the Johansen test
      confirm the presence of a long-run relationship among the variables under
      investigation. The stability of estimated parameters has been tested, while
      Granger causality tests recommend a short-run unidirectional causality running
      from economic growth and combustible renewables and waste consumption to CO2
      emissions, a bidirectional causality between economic growth and combustible
      renewables and waste consumption and unidirectional causality running from
      economic growth and combustible renewables and waste consumption to international
      tourism. In the long-run, the error correction terms confirm the presence of
      bidirectional causality relationships between economic growth, CO2 emissions,
      combustible renewables and waste consumption, and international tourism. Our long
      run estimates show that combustible renewables and waste consumption increases
      international tourism, and both renewables and waste consumption and
      international tourism increase CO2 emissions and output. We recommend that (i)
      Tunisia should use more combustible renewables and waste energy as this
      eliminates wastes from touristic zones and increases the number of tourist
      arrivals, leading to economic growth, and (ii) a fraction of this economic growth
      generated by the increase in combustible renewables and waste consumption should
      be invested in clean renewable energy production (i.e., solar, wind, geothermal)
      and energy efficiency projects. 

PMID- 25874439
TI  - Nonylphenol biodegradation, functional gene abundance and bacterial community in
      bioaugmented sediment: effect of external carbon source.
AB  - Nonylphenol (NP) biodegradation in river sediment using Stenotrophomonas strain
      Y1 and Sphingobium strain Y2 were proved to be an effective strategy to remediate
      NP pollution in our earlier study. The purpose of this study is to investigate
      the influence of glucose addition on their ability to degrade NP in both liquid
      cultures and sediment microcosms. The shift in bacterial community structure and
      relative abundance of NP degraders in sediment microcosms were characterized
      using terminal restriction fragment length polymorphism analysis. The proportion
      of NP-degrading alkB and sMO genes was assessed using quantitative polymerase
      chain reaction (PCR) assay. The growth of Stenotrophomonas strain Y1 and its NP
      biodegradation efficiency were inhibited by glucose supplementation, while the
      relative abundance of alkB gene increased. However, NP degradation, as well as
      the growth of added degraders and proportion of sMO gene, was enhanced in the
      glucose-amended sediment microcosms inoculated with Sphingobium strain Y2.
      Moreover, external glucose addition altered bacterial community structures in
      bioaugmented sediment microcosms, depending on the level of glucose dosage. 

PMID- 25874438
TI  - The effect of excess copper on growth and physiology of important food crops: a
      review.
AB  - In recent years, copper (Cu) pollution in agricultural soils, due to arbitrary
      use of pesticides, fungicides, industrial effluent and wastewater irrigation,
      present a major concern for sustainable agrifood production especially in
      developing countries. The world's major food requirement is fulfilled through
      agricultural food crops. The Cu-induced losses in growth and yield of food crops
      probably exceeds from all other causes of food safety and security threats. Here,
      we review the adverse effects of Cu excess on growth and yield of essential food
      crops. Numerous studies reported the Cu-induced growth inhibition, oxidative
      damage and antioxidant response in agricultural food crops such as wheat, rice,
      maize, sunflower and cucumber. This article also describes the toxic levels of Cu
      in crops that decreased plant growth and yield due to alterations in mineral
      nutrition, photosynthesis, enzyme activities and decrease in chlorophyll
      biosynthesis. The response of various crops to elevated Cu concentrations varies
      depending upon nature of crop and cultivars used. This review could be helpful to
      understand the Cu toxicity and the mechanism of its tolerance in food crops. We
      recommend that Cu-tolerant crops should be grown on Cu-contaminated soils in
      order to ameliorate the toxic effects for sustainable farming systems and to meet
      the food demands of the intensively increasing population. 

PMID- 25874440
TI  - Perceived descriptive safety-related driving norms within and outside Arab towns
      and villages in Israel.
AB  - OBJECTIVE: Involvement in car crashes is higher among Israeli Arabs compared to
      Jews. This study characterized perceived descriptive driving norms (PDDNs) within
      and outside Arab towns/villages and estimated their association with involvement
      in car crashes. METHODS: Arab drivers (594) living in 19 towns and villages were
      interviewed in face-to-face interviews. The questionnaire included questions
      about involvement in car crashes, PDDNs within and outside the towns/villages,
      attitudes toward traffic safety laws, traffic law violations, and socioeconomic
      and demographic variables. PDDNs represent individuals' perceptions on how safe
      other people typically drive. The low scores indicate a low percentage of drivers
      performing unsafe behaviors (safer driving-related norms). A structural equation
      modeling analysis was applied to identify factors associated with PDDNs and
      involvement in car crashes. RESULTS: A large difference was found in PDDNs within
      and outside the towns/villages. Mostly, the respondents reported higher rates of
      unsafe PDDNs within the towns/villages (mean = 3.76, SD = 0.63) and lower rates
      of PDDNs outside the towns/villages (mean = 2.12, SD = 0.60). PDDNs outside the
      towns/villages were associated with involvement in a car crash (r = -0.12, P
      <.01), but those within the towns/villages were not. Within the towns/villages,
      attitudes toward traffic laws and PDDNs were positively associated with traffic
      law violations (r = 0.56, P <.001; r = 0.11, P <.001 respectively), where traffic
      law violations were directly associated with involvement in a car crash (r = 
      0.14, P <.001). CONCLUSIONS: Unsafe PDDNs may add directly and indirectly to
      unsafe driving and involvement in car crashes in Arab Israelis. Because PDDNs
      outside towns/villages were better, increased law enforcement within
      towns/villages may improve these norms and decrease involvement in car crashes.

PMID- 25874441
TI  - Danish holsteins favor bull offspring: biased milk production as a function of
      fetal sex, and calving difficulty.
AB  - In a previous study from 2014 it was found that US Holstein cows that gave birth
      to heifer calves produced more milk than cows having bull calves. We wanted to
      assess whether this is also true for Danish cattle. Data from 578 Danish Holstein
      herds were analysed with a mixed effect model and contrary to the findings in the
      US, we found that cows produced higher volumes of milk if they had a bull calf
      compared to a heifer calf. We found a significantly higher milk production of
      0.28% in the first lactation period for cows giving birth to a bull calf,
      compared to a heifer calf. This difference was even higher when cows gave birth
      to another bull calf, so having two bull calves resulted in a difference of 0.52%
      in milk production compared to any other combination of sex of the offspring.
      Furthermore, we found that farmer assisted calvings were associated with a higher
      milk yield. Cows with no farmer assistance or with veterinary assistance during
      the most recent calving produced less milk. There were also indications that dams
      would favor a bull fetus by decreasing milk production during the second
      pregnancy if the calf born in the first parity was a heifer. We hypothesize that
      size of calves is a confounding factor for milk production. However, calving
      weight was not available in the present data set to test this hypothesis. 

PMID- 25874442
TI  - [Differential diagnosis of anal eczema].
AB  - Dermatologic disorders often show involvement of the (peri)anal skin. However,
      diagnosis of (peri)anal dermatoses is often difficult even for experienced
      dermatologists due to delayed clinical presentation or prior treatment with over
      the-counter medications. The distinct anatomical conditions of the (peri)anal
      region results in atypical clinical presentation of common dermatoses. Typical
      symptoms include pruritus, burning, bleeding and pain. Careful history of
      symptoms, stool, hygiene, sexual practice as well as thorough inspection of the
      entire body and proctological examination are crucial to make the correct
      diagnosis. In case of atypical presentation or uncertainty a biopsy needs to be
      obtained to ensure correct diagnosis and treatment. 

PMID- 25874443
TI  - Substrate-bound growth of Au-Pd diblock nanowire and hybrid nanorod-plate.
AB  - We expand the scope of the previously developed Active Surface Growth mode for
      growing substrate-bound ultrathin Pd (d = 4 nm) and Ag nanowires (d = 30 nm) in
      aqueous solution under ambient conditions. Using Au nanorods as the seeds,
      selective growth at the contact line between the rod and the substrate eventually
      leads to an attached Pd nanoplate. The unique growth mode also allows sequential
      growth of different materials via a single seed, giving substrate-bound Au-Pd
      diblock nanowires. The new abilities to use seed shape to pre-define the active
      sites and to apply sequential growth open windows for new pathways to hybrid
      nanostructures. 

PMID- 25874444
TI  - Mitochondrial succinate dehydrogenase is involved in stimulus-secretion coupling
      and endogenous ROS formation in murine beta cells.
AB  - AIMS/HYPOTHESIS: Generation of reduction equivalents is a prerequisite for
      nutrient-stimulated insulin secretion. Mitochondrial succinate dehydrogenase
      (SDH) fulfils a dual function with respect to mitochondrial energy supply: (1)
      the enzyme is part of mitochondrial respiratory chains; and (2) it catalyses
      oxidation of succinate to fumarate in the Krebs cycle. The aim of our study was
      to elucidate the significance of SDH for beta cell stimulus-secretion coupling
      (SSC). METHODS: Mitochondrial variables, reactive oxygen species (ROS) and
      cytosolic Ca(2+) concentration ([Ca(2+)]c) were measured by fluorescence
      techniques and insulin release by radioimmunoassay in islets or islet cells of
      C57Bl/6N mice. RESULTS: Inhibition of SDH with 3-nitropropionic acid (3-NPA) or
      monoethyl fumarate (MEF) reduced glucose-stimulated insulin secretion. Inhibition
      of the ATP-sensitive K(+) channel (KATP channel) partly prevented this effect,
      whereas potentiation of antioxidant defence by superoxide dismutase mimetics
      (TEMPOL and mito-TEMPO) or by nuclear factor erythroid 2-related factor 2 (Nrf-2)
      mediated upregulation of antioxidant enzymes (oltipraz, tert-butylhydroxyquinone)
      did not diminish the inhibitory influence of 3-NPA. Blocking SDH decreased
      glucose-stimulated increase in intracellular FADH2 concentration without
      alterations in NAD(P)H. In addition, 3-NPA and MEF drastically reduced glucose
      induced hyperpolarisation of mitochondrial membrane potential, indicative of
      decreased ATP production. As a consequence, the glucose-stimulated rise in
      [Ca(2+)]c was significantly delayed and reduced. Acute application of 3-NPA
      interrupted glucose-driven oscillations of [Ca(2+)]c. 3-NPA per se did not
      elevate intracellular ROS, but instead prevented glucose-induced ROS
      accumulation. CONCLUSIONS/INTERPRETATION: SDH is an important regulator of
      insulin secretion and ROS production. Inhibition of SDH interrupts membrane
      potential-dependent SSC, pointing to a pivotal role of mitochondrial FAD/FADH2
      homeostasis for the maintenance of glycaemic control.

PMID- 25874445
TI  - LKB1 couples glucose metabolism to insulin secretion in mice.
AB  - AIMS/HYPOTHESIS: Precise regulation of insulin secretion by the pancreatic beta
      cell is essential for the maintenance of glucose homeostasis. Insulin secretory
      activity is initiated by the stepwise breakdown of ambient glucose to increase
      cellular ATP via glycolysis and mitochondrial respiration. Knockout of Lkb1, the
      gene encoding liver kinase B1 (LKB1) from the beta cell in mice enhances insulin
      secretory activity by an undefined mechanism. Here, we sought to determine the
      molecular basis for how deletion of Lkb1 promotes insulin secretion. METHODS: To
      explore the role of LKB1 on individual steps in the insulin secretion pathway, we
      used mitochondrial functional analyses, electrophysiology and metabolic tracing
      coupled with by gas chromatography and mass spectrometry. RESULTS: Beta cells
      lacking LKB1 surprisingly display impaired mitochondrial metabolism and lower ATP
      levels following glucose stimulation, yet compensate for this by upregulating
      both uptake and synthesis of glutamine, leading to increased production of
      citrate. Furthermore, under low glucose conditions, Lkb1(-/-) beta cells fail to
      inhibit acetyl-CoA carboxylase 1 (ACC1), the rate-limiting enzyme in lipid
      synthesis, and consequently accumulate NEFA and display increased membrane
      excitability. CONCLUSIONS/INTERPRETATION: Taken together, our data show that LKB1
      plays a critical role in coupling glucose metabolism to insulin secretion, and
      factors in addition to ATP act as coupling intermediates between feeding cues and
      secretion. Our data suggest that beta cells lacking LKB1 could be used as a
      system to identify additional molecular events that connect metabolism to
      cellular excitation in the insulin secretion pathway.

PMID- 25874446
TI  - Mapping trabecular disconnection "hotspots" in aged human spine and hip.
AB  - Trabecular bone disconnection is an independent factor in age-related skeletal
      failure where real termini (ReTm; rare in youth) may cause weakness
      disproportionate to tissue loss, yet their structural contribution at vulnerable
      locations remains uncertain. ReTm (previously recorded at the iliac crest) were
      mapped in "normal" aged vertebral bodies (T11-L5 autopsy; 20 females, 10 males)
      and corresponding proximal femora (autopsy; 10 females). Results were compared
      with biomechanically failed femora from orthopaedic subjects aged >58 yr
      (osteoporosis OP, 10 females; osteoarthritis OA, 10 females). A novel direct
      2D/3D histological method was applied to large, thick (300 MUm) slices
      superficially silver-stained to separate ReTm (unstained) from apparent termini
      (planar artefacts, brown). Light microscope field co-ordinates enabled ReTm
      mapping and statistical testing relative to i) sex, ii) tissue sector and iii)
      slicing plane. In men ReTm populations were small and random while in women they
      were large and sector-specific. In vertebrae they clustered anterior/superior
      being rare posterior/inferior; in the femoral head they concentrated
      distal/superior and also near the fovea, being fewer distal/inferior. A
      distribution polarity was evident with 100% more ReTm observed transversely
      (i.e., on tensile-related cross struts) than longitudinally (i.e., on compression
      related vertical struts). Their numbers rose in OP (BV/TV<14%, microCT) and in OA
      (BV/TV>14%), remaining polarised and sector-specific in OP only. Comparative
      experimentation by marrow elution of an OP animal model demonstrated "floating
      segments" as a possible outcome. Conclusions were supported statistically that
      trabecular disconnection "hotspots" at vulnerable locations are sex- and sector
      specific, mainly transaxial, and subject to disease modulation.

PMID- 25874447
TI  - Quantitative determination of technological improvement from patent data.
AB  - The results in this paper establish that information contained in patents in a
      technological domain is strongly correlated with the rate of technological
      progress in that domain. The importance of patents in a domain, the recency of
      patents in a domain and the immediacy of patents in a domain are all strongly
      correlated with increases in the rate of performance improvement in the domain of
      interest. A patent metric that combines both importance and immediacy is not only
      highly correlated (r = 0.76, p = 2.6*10(-6)) with the performance improvement
      rate but the correlation is also very robust to domain selection and appears to
      have good predictive power for more than ten years into the future. Linear
      regressions with all three causal concepts indicate realistic value in practical
      use to estimate the important performance improvement rate of a technological
      domain.

PMID- 25874448
TI  - Prussian blue without coordinated water as a superior cathode for sodium-ion
      batteries.
AB  - A micro-cubic Prussian blue (PB) without coordinated water is first developed by
      electron exchange between graphene oxide and PB. The obtained reduced graphene
      oxide-PB composite exhibited complete redox reactions of the Fe sites and
      delivered ultrahigh electrochemical performances as well as excellent cycling
      stability as a cathode in sodium-ion batteries. 

PMID- 25874449
TI  - Rosiglitzone suppresses angiotensin II-induced production of KLF5 and cell
      proliferation in rat vascular smooth muscle cells.
AB  - Kruppel-like factor (KLF) 5, which initiates vascular smooth muscle cell (VSMC)
      proliferation, also participates in Angiotensin (Ang) II-induced vascular
      remodeling. The protective effect of rosiglitazone on vascular remodeling may be
      due to their impact on VSMC proliferation. However, the underlying mechanisms
      involved remain unclear. This study was designed to investigate whether the
      antiproliferation effects of rosiglitazone are mediated by regulating Ang II/KLF5
      response. We found that, in aortas of Ang II-infused rats, vascular remodeling
      and KLF5 expression were markedly increased, and its target gene cyclin D1 was
      overexpressed. Co-treatment with rosiglitazone diminished these changes. In
      growth-arrested VSMCs, PPAR-gamma agonists (rosiglitazone and 15d-PGJ2) dose
      dependently inhibited Ang II-induced cell proliferation and expression of KLF5
      and cyclin D1. Moreover, these effects were attenuated by the PPAR-gamma
      antagonists GW9662, bisphenol A diglycidyl ether and PPAR-gamma specific siRNA.
      Furthermore, rosiglitazone inhibited Ang II-induced phosphorylation of protein
      kinase C (PKC) zeta and extracellular signal-regulated kinase (ERK) 1/2 and
      activation of early growth response protein (Egr). In conclusion, in Ang II
      stimulated VSMCs, rosiglitazone might have an antiproliferative effect through
      mechanisms that include reducing KLF5 expression, and a crosstalk between PPAR
      gamma and PKCzeta/ERK1/2/Egr may be involved in. These findings not only provide
      a previously unrecognized mechanism by which PPAR-gamma agonists inhibit VSMC
      proliferation, but also document a novel evidence for the beneficial vascular
      effect of PPAR-gamma activation. 

PMID- 25874451
TI  - Correction: mapping forest fuels through vegetation phenology: the role of coarse
      resolution satellite time-series.

PMID- 25874450
TI  - Elevated high-sensitivity C-reactive protein levels predict decreased survival
      for nasopharyngeal carcinoma patients in the intensity-modulated radiotherapy
      era.
AB  - PURPOSE: This study aimed to clarify the prognostic utility of high-sensitivity C
      reactive protein (hs-CRP) in nasopharyngeal carcinoma (NPC) patients in the
      Intensity-Modulated Radiotherapy (IMRT) era. PATIENTS AND METHODS: In this
      observational study, 1,589 non-metastatic NPC patients treated with IMRT were
      recruited. Blood samples were collected before treatment for examination of hs
      CRP levels. We evaluated the association of pretreatment hs-CRP levels with
      overall survival rate (OS), progression free survival rate (PFS), locoregional
      relapse free survival rate (LRFS) and distant metastasis free survival rate
      (DMFS). RESULTS: Baseline hs-CRP levels were correlated with sex, clinical stage,
      body mass index, smoking status, and EBV DNA level. Multivariate analysis showed
      that hs-CRP had significant association with OS (HR:1.723; 95%CI:1.238-2.398; p =
      0.001), PFS (HR:1.621; 95%CI:1.273-2.064; p<0.001) and DMFS (HR:1.879;
      95%CI:1.394-2.531; p<0.001). In subgroups such as advanced-stage group, low EBV
      DNA group and high EBV DNA group, elevated hs-CRP levels still predicted poor
      clinical outcomes. Furthermore, in patients with chronic HBV infection, decreased
      4-year survival was observed in the cohort of high hs-CRP levels, with 87.4% vs.
      94.9% (p = 0.023) for OS, 65.2% vs. 90.8% (p<0.001) for PFS, and 67.6% vs. 95.0%
      (p<0.001) for DMFS. A similar finding was observed for patients with
      cardiovascular disease, with 79.1% vs. 90.2% (p = 0.020) for PFS, and 71.4% vs.
      97.6% (p = 0.002) for DMFS. CONCLUSION: Elevated serum hs-CRP levels were
      correlated with poor survival for NPC patients in the IMRT era, playing a
      complementary role to TNM stage and EBV DNA. In addition, elevated hs-CRP level
      was still an effective indicator for patients with chronic HBV infection and
      cardiovascular disease.

PMID- 25874453
TI  - Correlative stochastic optical reconstruction microscopy and electron microscopy.
AB  - Correlative fluorescence light microscopy and electron microscopy allows the
      imaging of spatial distributions of specific biomolecules in the context of
      cellular ultrastructure. Recent development of super-resolution fluorescence
      microscopy allows the location of molecules to be determined with nanometer-scale
      spatial resolution. However, correlative super-resolution fluorescence microscopy
      and electron microscopy (EM) still remains challenging because the optimal
      specimen preparation and imaging conditions for super-resolution fluorescence
      microscopy and EM are often not compatible. Here, we have developed several
      experiment protocols for correlative stochastic optical reconstruction microscopy
      (STORM) and EM methods, both for un-embedded samples by applying EM-specific
      sample preparations after STORM imaging and for embedded and sectioned samples by
      optimizing the fluorescence under EM fixation, staining and embedding conditions.
      We demonstrated these methods using a variety of cellular targets. 

PMID- 25874452
TI  - Defining the minimal important difference for the visual analogue scale assessing
      dyspnea in patients with malignant pleural effusions.
AB  - BACKGROUND: The minimal important difference (MID) is essential for interpreting
      the results of randomised controlled trials (RCTs). Despite a number of RCTs in
      patients with malignant pleural effusions (MPEs) which use the visual analogue
      scale for dyspnea (VASD) as an outcome measure, the MID has not been established.
      METHODS: Patients with suspected MPE undergoing a pleural procedure recorded
      their baseline VASD and their post-procedure VASD (24 hours after the pleural
      drainage), and in parallel assessed their breathlessness on a 7 point Likert
      scale. FINDINGS: The mean decrease in VASD in patients with a MPE reporting a
      'small but just worthwhile decrease' in their dyspnea (i.e. equivalent to the
      MID) was 19mm (95% CI 14-24mm). The mean drainage volume required to produce a
      change in VASD of 19mm was 760ml. INTERPRETATION: The mean MID for the VASD in
      patients with a MPE undergoing a pleural procedure is 19mm (95% CI 14-24mm). Thus
      choosing an improvement of 19mm in the VASD would be justifiable in the design
      and analysis of future MPE studies.

PMID- 25874454
TI  - The impact of diabetes mellitus and corresponding HbA1c levels on the future
      risks of cardiovascular disease and mortality: a representative cohort study in
      Taiwan.
AB  - BACKGROUND: This study explored the relationship between the glycated hemoglobin
      (HbA1c) level in patients with or without diabetes mellitus and future risks of
      cardiovascular disease and death. METHODS: Based on a national representative
      cohort, a total of 5277 participants (7% with diabetes) were selected from
      Taiwan's Triple High Survey in 2002. The comorbidities, medication usages, and
      outcomes of cardiovascular disease and death, were extracted from the Taiwan's
      National Health Insurance Research Database and National Death Registry. RESULTS:
      After a median follow-up of 9.7 years, participants with diabetes had higher
      incidence of new onset cardiovascular disease (17.9 versus 3.16 cases per 1000
      person-years) and death (20.1 versus 4.96 cases per 1000 person-years) than those
      without diabetes (all P < 0.001). Diabetes showed increased risk of all-cause
      death after adjusting for all confounders (adjusted hazard ratio [HR]: 2.29, 95%
      confidence interval [CI]: 1.52-3.45). Every 1% increment of HbA1c was positively
      associated with the risk of total cardiovascular disease (HR: 1.2, 95% CI: 1.08
      1.34) and the risk of death (HR: 1.14, 95% CI: 1.03-1.26) for all participants.
      As compared to the reference group with HbA1c below 5.5%, participants with HbA1c
      levels >=7.5% had significantly elevated future risks of total cardiovascular
      disease (HR: 1.82, 95% CI: 1.01-3.26) and all-cause death (HR: 2.45, 95% CI: 1.45
      4.14). CONCLUSIONS/INTERPRETATION: Elevated HbA1C levels were associated with
      increased risks of cardiovascular disease and death, the suboptimal glycemic
      control with HbA1c level over 7.5% (58.5 mmol/mol) was strongly associated with
      increased risks of cardiovascular disease and all-cause death.

PMID- 25874455
TI  - Genome-wide transcriptome and expression profile analysis of Phalaenopsis during
      explant browning.
AB  - BACKGROUND: Explant browning presents a major problem for in vitro culture, and
      can lead to the death of the explant and failure of regeneration. Considerable
      work has examined the physiological mechanisms underlying Phalaenopsis leaf
      explant browning, but the molecular mechanisms of browning remain elusive. In
      this study, we used whole genome RNA sequencing to examine Phalaenopsis leaf
      explant browning at genome-wide level. METHODOLOGY/PRINCIPAL FINDINGS: We first
      used Illumina high-throughput technology to sequence the transcriptome of
      Phalaenopsis and then performed de novo transcriptome assembly. We assembled
      79,434,350 clean reads into 31,708 isogenes and generated 26,565 annotated
      unigenes. We assigned Gene Ontology (GO) terms, Kyoto Encyclopedia of Genes and
      Genomes (KEGG) annotations, and potential Pfam domains to each transcript. Using
      the transcriptome data as a reference, we next analyzed the differential gene
      expression of explants cultured for 0, 3, and 6 d, respectively. We then
      identified differentially expressed genes (DEGs) before and after Phalaenopsis
      explant browning. We also performed GO, KEGG functional enrichment and Pfam
      analysis of all DEGs. Finally, we selected 11 genes for quantitative real-time
      PCR (qPCR) analysis to confirm the expression profile analysis.
      CONCLUSIONS/SIGNIFICANCE: Here, we report the first comprehensive analysis of
      transcriptome and expression profiles during Phalaenopsis explant browning. Our
      results suggest that Phalaenopsis explant browning may be due in part to gene
      expression changes that affect the secondary metabolism, such as: phenylpropanoid
      pathway and flavonoid biosynthesis. Genes involved in photosynthesis and ATPase
      activity have been found to be changed at transcription level; these changes may
      perturb energy metabolism and thus lead to the decay of plant cells and tissues.
      This study provides comprehensive gene expression data for Phalaenopsis browning.
      Our data constitute an important resource for further functional studies to
      prevent explant browning.

PMID- 25874457
TI  - Formulation and application of optimal homotopty asymptotic method to coupled
      differential-difference equations.
AB  - In this paper we applied a new analytic approximate technique Optimal Homotopy
      Asymptotic Method (OHAM) for treatment of coupled differential-difference
      equations (DDEs). To see the efficiency and reliability of the method, we
      consider Relativistic Toda coupled nonlinear differential-difference equation. It
      provides us a convenient way to control the convergence of approximate solutions
      when it is compared with other methods of solution found in the literature. The
      obtained solutions show that OHAM is effective, simpler, easier and explicit.

PMID- 25874456
TI  - A wrench in the works of human acetylcholinesterase: soman induced conformational
      changes revealed by molecular dynamics simulations.
AB  - Irreversible inactivation of human acetylcholinesterase (hAChE) by
      organophosphorous pesticides (OPs) and chemical weapon agents (CWA) has severe
      morbidity and mortality consequences. We present data from quantum
      mechanics/molecular mechanics (QM/MM) and 80 classical molecular dynamics (MD)
      simulations of the apo and soman-adducted forms of hAChE to investigate the
      effects on the dynamics and protein structure when the catalytic Serine 203 is
      phosphonylated. We find that the soman phosphonylation of the active site Ser203
      follows a water assisted addition-elimination mechanism with the elimination of
      the fluoride ion being the highest energy barrier at 6.5 kcal/mole. We observe
      soman-dependent changes in backbone and sidechain motions compared to the apo
      form of the protein. These alterations restrict the soman-adducted hAChE to a
      structural state that is primed for the soman adduct to be cleaved and removed
      from the active site. The altered motions and resulting structures provide
      alternative pathways into and out of the hAChE active site. In the soman-adducted
      protein both side and back door pathways are viable for soman adduct access.
      Correlation analysis of the apo and soman adducted MD trajectories shows that the
      correlation of gorge entrance and back door motion is disrupted when hAChE is
      adducted. This supports the hypothesis that substrate and product can use two
      different pathways as entry and exit sites in the apo form of the protein. These
      alternative pathways have important implications for the rational design of
      medical countermeasures. 

PMID- 25874458
TI  - Sintered indium-tin oxide particles induce pro-inflammatory responses in vitro,
      in part through inflammasome activation.
AB  - Indium-tin oxide (ITO) is used to make transparent conductive coatings for touch
      screen and liquid crystal display electronics. As the demand for consumer
      electronics continues to increase, so does the concern for occupational exposures
      to particles containing these potentially toxic metal oxides. Indium-containing
      particles have been shown to be cytotoxic in cultured cells and pro-inflammatory
      in pulmonary animal models. In humans, pulmonary alveolar proteinosis and
      fibrotic interstitial lung disease have been observed in ITO facility workers.
      However, which ITO production materials may be the most toxic to workers and how
      they initiate pulmonary inflammation remain poorly understood. Here we examined
      four different particle samples collected from an ITO production facility for
      their ability to induce pro-inflammatory responses in vitro. Tin oxide, sintered
      ITO (SITO), and ventilation dust particles activated nuclear factor kappa B
      (NFkappaB) within 3 h of treatment. However, only SITO induced robust cytokine
      production (IL-1beta, IL-6, TNFalpha, and IL-8) within 24 h in both RAW 264.7
      mouse macrophages and BEAS-2B human bronchial epithelial cells. Our lab and
      others have previously demonstrated SITO-induced cytotoxicity as well. These
      findings suggest that SITO particles activate the NLRP3 inflammasome, which has
      been implicated in several immune-mediated diseases via its ability to induce IL
      1beta release and cause subsequent cell death. Inflammasome activation by SITO
      was confirmed, but it required the presence of endotoxin. Further, a phagocytosis
      assay revealed that pre-uptake of SITO or ventilation dust impaired proper
      macrophage phagocytosis of E. coli. Our results suggest that adverse inflammatory
      responses to SITO particles by both macrophage and epithelial cells may initiate
      and propagate indium lung disease. These findings will provide a better
      understanding of the molecular mechanisms behind an emerging occupational health
      issue. 

PMID- 25874459
TI  - Knowledge, attitudes and practice of desalinated water among professionals in
      health and water departments in Shengsi, China: a qualitative study.
AB  - Desalination has been considered as an essential way to solve water stress all
      over the world. Most of previous studies focused on its environmental impacts,
      energy consumption and desalination technologies rather than human health.
      However, the safety of desalinated water remains unclear. This study was
      undertaken to investigate the knowledge, attitude and practice (KAP) of the
      residents in an island county in eastern China to desalinated water. Seventeen
      people working in medical and water industries were recruited, and focus group
      discussion and in-depth interview were conducted among them. Our results showed
      that the majority of people interviewed knew the definition and local supply
      pattern of desalinated water, while some of them showed some concern about the
      safety and nutrition of desalinated water. Current drinking water standard has no
      specific item for desalination, so we strongly suggest issuing a standard for
      desalinated water. 

PMID- 25874461
TI  - A new synthesis for dual use research of concern.

PMID- 25874460
TI  - Role of preoperative intravenous iron therapy to correct anemia before major
      surgery: study protocol for systematic review and meta-analysis.
AB  - BACKGROUND: Preoperative anemia is a common and potentially serious hematological
      problem in elective surgery and increases the risk for perioperative red blood
      cell (RBC) transfusion. Transfusion is associated with postoperative morbidity
      and mortality. Preoperative intravenous (IV) iron therapy has been proposed as an
      intervention to reduce perioperative transfusion; however, studies are generally
      small, limited, and inconclusive. METHODS/DESIGN: We propose performing a
      systematic review and meta-analysis. We will search MEDLINE, EMBASE, EBM Reviews,
      Cochrane-controlled trial registry, Scopus, registries of health technology
      assessment and clinical trials, Web of Science, ProQuest Dissertations and
      Theses, and conference proceedings in transfusion, hematology, and surgery. We
      will contact our study drug manufacturer for unpublished trials. Titles and
      abstracts will be identified and assessed by two reviewers for potential
      relevance. Eligible studies are: randomized or quasi-randomized clinical trials
      comparing preoperative administration of IV iron with placebo or standard of care
      to reduce perioperative blood transfusion in anemic patients undergoing major
      surgery. Screening, data extraction, and quality appraisal will be conducted
      independently by two authors. Data will be presented in evidence tables and in
      meta-analytic forest plots. Primary efficacy outcomes are change in hemoglobin
      concentration and proportion of patients requiring RBC transfusion. Secondary
      outcomes include number of units of blood or blood products transfused
      perioperatively, transfusion-related acute lung injury, neurologic complications,
      adverse events, postoperative infections, cardiopulmonary complications,
      intensive care unit (ICU) admission/readmission, length of hospital stay, acute
      kidney injury, and mortality. Dichotomous outcomes will be reported as pooled
      relative risks and 95% confidence intervals. Continuous outcomes will be reported
      using calculated weighted mean differences. Meta-regression will be performed to
      evaluate the impact of potential confounding variables on study effect estimates.
      DISCUSSION: Reducing unnecessary RBC transfusions in perioperative medicine is a
      clinical priority. This involves the identification of patients at risk of
      receiving transfusions along with blood conservation strategies. Of potential
      pharmacological blood conservation strategies, IV iron is a compelling
      intervention to treat preoperative anemia; however, existing data are uncertain.
      We propose performing a systematic review and meta-analysis evaluating the
      efficacy and safety of IV iron administration to anemic patients undergoing major
      surgery to reduce transfusion and perioperative morbidity and mortality.
      SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015016771.

PMID- 25874463
TI  - [Not Available].
AB  - A total contact cast (TCC) is considered the gold standard for healing diabetic
      foot ulcers (DFU). Numerous studies have demonstrated the excellent healing
      success of a TCC; however, its adoption in routine clinical use does not match
      its success rate. This lack of implementation is due to several factors:
      Medicare's payment structure, lack of clinical training, and a variety of patient
      factors. These factors have reduced clinicians' use of TCC to approximately 25%
      of DFU. The aim of this review was to analyze and demonstrate common scenarios
      for outpatient wound centers where a TCC may be beneficial to both patients and
      hospital systems, and to expand its usage to more closely reflect its healing
      success rate.    . 

PMID- 25874462
TI  - Quadruple quorum-sensing inputs control Vibrio cholerae virulence and maintain
      system robustness.
AB  - Bacteria use quorum sensing (QS) for cell-cell communication to carry out group
      behaviors. This intercellular signaling process relies on cell density-dependent
      production and detection of chemical signals called autoinducers (AIs). Vibrio
      cholerae, the causative agent of cholera, detects two AIs, CAI-1 and AI-2, with
      two histidine kinases, CqsS and LuxQ, respectively, to control biofilm formation
      and virulence factor production. At low cell density, these two signal receptors
      function in parallel to activate the key regulator LuxO, which is essential for
      virulence of this pathogen. At high cell density, binding of AIs to their
      respective receptors leads to deactivation of LuxO and repression of virulence
      factor production. However, mutants lacking CqsS and LuxQ maintain a normal LuxO
      activation level and remain virulent, suggesting that LuxO is activated by
      additional, unidentified signaling pathways. Here we show that two other
      histidine kinases, CqsR (formerly known as VC1831) and VpsS, act upstream in the
      central QS circuit of V. cholerae to activate LuxO. V. cholerae strains
      expressing any one of these four receptors are QS proficient and capable of
      colonizing animal hosts. In contrast, mutants lacking all four receptors are
      phenotypically identical to LuxO-defective mutants. Importantly, these four
      functionally redundant receptors act together to prevent premature induction of a
      QS response caused by signal perturbations. We suggest that the V. cholerae QS
      circuit is composed of quadruple sensory inputs and has evolved to be refractory
      to sporadic AI level perturbations. 

PMID- 25874464
TI  - [Not Available].
AB  - Autonomic dysreflexia (AD) is an acute, life-threatening syndrome of uncontrolled
      sympathetic discharge that occurs in patients with spinal cord injury at T6 or
      higher. Despite a high incidence in tetraplegics, the condition is under
      recognized, putting both the practitioner and patient at risk. This report
      presents a case of AD triggered by debridement of a pressure ulcer. To advance
      the understanding among wound care practitioners, the authors review the
      literature, describe the common clinical presentations and scenarios leading to
      AD, delineate a protocol to guide management, and conclude with a discussion of
      potential preventative measures.  . 

PMID- 25874465
TI  - [Not Available].
AB  - The aim of this retrospective study was to identify risk factors related to
      unsuccessful treatment and complications with negative pressure wound therapy
      (NPWT). METHODS: A consecutive series of patients treated with NPWT for wounds of
      various etiologies (n = 87) from 2005-2007 at a general hospital in a large city
      (Stockholm, Sweden) were assessed for risk for unsuccessful treatment and
      complications associated with NPWT. RESULTS: Twenty-nine percent of the patients
      treated with NPWT had unsuccessful treatment results. The strongest risk factors
      associated with unsuccessful treatment were pressure ulcers (OR 4.6) or a
      positive culture for Staphylococci (OR 3.4). The complication rate was 21%, of
      which 14 patients had to terminate treatment. A positive culture for either
      Staphylococci or Pseudomonas was strongly associated (P = 0.001) with risk of
      complications during NPWT treatment. Patients with insufficient peripheral
      circulation in the extremities had a risk of both unsuccessful treatment and
      complications. CONCLUSION: The findings of the present study stress the
      importance of evaluating bacterial cultures and adequate antibiotic therapy when
      infection is suspected. The status of the patient's peripheral macrocirculation
      in the lower extremities seems to have a significant impact on the risk of
      unsuccessful treatment or complications. Therefore, is it of great importance to
      evaluate peripheral circulation status before initializing NPWT.    .

PMID- 25874466
TI  - [Appleby operation for locally advanced tumour of the pancreatic body and tail--a
      video demonstration].
AB  - INTRODUCTION: Patients with locally advanced pancreatic cancer and arterial
      infiltration of the coeliac artery are often classified as irresectable and
      therefore treated palliatively. For a highly selected group of patients, a
      complete resection (R0) of a pancreatic carcinoma including resection of the
      coeliac trunk without arterial reconstruction can mean a survival advantage. The
      expertise of the surgeon in vascular and pancreatic surgery as well as the
      proficiency of the entire surgical and anaesthesiological team and the
      appropriate infrastructure of the hospital are prerequisites for the success of
      such complex operations. Concerning the local finding of infiltration of the
      aorta, the gastroduodenal artery and the mesenteric superior artery should be
      excluded, to ensure R0 resection and perfusion of the liver via the
      gastroduodenal artery after resection. Moreover, the patient has to be fit for a
      large abdominal operation and extrapancreatic metastases have to be excluded,
      especially in ductal adenocarcinoma of the pancreas. In this video, the
      principles of the Appleby operation are shown in a case of locally advanced
      neuroendocrine carcinoma of the pancreas with infiltration of the coeliac artery.
      INDICATION: Locally advanced pancreatic neuroendocrine carcinoma with
      infiltration of the coeliac artery without distant metastasis after neoadjuvant
      therapy. PROCEDURE: Extended multiorgan pancreatic corpus and tail resection
      including resection of coeliac artery, portal vein resection, splenectomy,
      resection of left adrenal gland, subtotal gastrectomy and oversewing of the
      pancreatic head, end-to-end reconstruction of the portal vein and gastro
      jejunostomy (Roux-Y) and duodeno-jejunostomy. CONCLUSION: Given the appropriate
      experience, the Appleby procedure is a technically demanding resection in
      pancreatic carcinomas involving the coeliac artery without arterial anastomosis.
      In selected cases this operation might have advantages compared to palliative
      treatment.

PMID- 25874467
TI  - [Plastic surgery (Congress Issue 2015)--editorial].

PMID- 25874468
TI  - [Options for reconstructive surgery of the thoracic wall].
AB  - The integrity of the thoracic wall and therefore the protection of the thoracic
      organs is paramount for survival. This integrity can be compromised by various
      factors, be it tumours, wound-healing disorders or injuries. An adequate surgical
      therapy for these entities often requires (partial) resections of the thoracic
      wall resulting in a loss of its protective function. A safe and timely
      reconstruction of the thoracic wall is therefore mandatory and can be achieved by
      means of reconstructive procedures. This article therefore aims to illustrate
      such reconstructive procedures utilising our own clinical cases while also giving
      a review of the literature in order to construct an algorithm for the
      reconstruction procedure. 

PMID- 25874469
TI  - [Therapeutic options for pressure ulcers].
AB  - The aim of this overview is based on remarks on the pathogenesis of and therapy
      for pressure ulcers and selected but representative cases to demonstrate current
      options of plastic coverage. As a consequence of the demographic developments, in
      particular, with regard to the increasing proportion of older patients as well as
      the advances in modern medicine, the number of multimorbid, geriatric and
      bedridden patients and of those with prolonged sickbed periods has been steadily
      growing. Therefore, partly severe manifestations of pressure ulcers at various
      exposed body regions can be observed in spite of the best preventive intention of
      care. While in the early stages rather conservative treatment is adequate,
      surgical intervention might become important and indispensable for a sufficient
      treatment in advanced stages. To facilitate basic care and to appropriately treat
      the infectious focus, the methods and procedures of plastic surgery can become
      relevant. Although there are several options and approaches existing to sanitise
      and cover defects of pressure ulcers, which are described within the article
      based on representative cases, preventive measures can still be considered the
      best approach. 

PMID- 25874470
TI  - [Plastic reconstructive options for chronic pilonidal disease].
AB  - INTRODUCTION: Chronic pilonidal disease represents an infectious disease of the
      gluteal cleft that often requires surgical resection. AIM: In this article,
      several plastic-surgical reconstructions are presented. METHODS AND RESULTS:
      Based on our experience and the current literature, different plastic surgical
      reconstructive methods are presented and discussed. Thorough debridement
      including sinus tracts and follicles represents an important step in the
      treatment algorithm. Subsequently, wide defects may remain that can require
      reconstructive surgery with local flaps. These may include a Karydakis procedure,
      Limberg transposition flap, V-Y advancement or rotation flap. CONCLUSION: After
      thorough debridement and adherence to plastic surgical principles, sufficient
      reconstructions can be obtained with the presented methods.

PMID- 25874471
TI  - [Plastic-surgical treatment options in necrotising fasciitis].
AB  - Necrotising fasciitis (NF) is considered a rare and possibly life-threatening
      infection of the subcutaneous tissue and of the fascia. A specific characteristic
      is the rapid progress of the disease associated with considerable local pain.
      Since laboratory parameters as well as imaging are only unspecific, diagnosis is
      set up clinically. Even in the case of a serious suspicion, an immediate and
      radical debridement has to be initiated, accompanied by intensive care and
      adequate antibiotic treatment. Only after stabilisation of the general physical
      condition and local - sometimes extensive - wound debridement, can coverage and
      reconstruction of soft tissue defects be appropriately performed by the measures
      and procedures of plastic surgery. 

PMID- 25874472
TI  - [Plastic surgery of extended defects after exenteration of the pelvis].
AB  - Extended resections of pelvic malignancies, especially in cases of recurrent
      malignancies, result in the formation of large tissue defects in the region of
      the pelvic floor and perineum, which are difficult to deal with. Both after extra
      levator rectal excision and pelvic exenteration, wound healing deficiencies and
      local infections of the perineal wound are frequent. Primary closure is often
      impossible due to a lack of tissue substance after resection and an additional
      previous radiotherapy in most cases. This can result in poor or non-healing
      wounds, a consecutive need of complex care and an increased risk of secondary
      problems including tumour recurrences. A permanent wound closure of good quality
      can therefore only be achieved by plastic surgery. This can be done by local or
      distant muscle flaps with or without skin, for example, the gluteus maximus flap,
      the vertical rectus abdominis muscle flap (VRAM) or free flaps such as the
      latissimus dorsi flap. 

PMID- 25874473
TI  - [Vascular medicine needs more evidence: recent results and meta-analyses for the
      treatment of diabetic feet].
AB  - BACKGROUND: This overview comments on clinical trials and meta-analyses from the
      literature on the treatment of diabetic feet. METHODS: For the literature review,
      the MEDLINE database (PUBMED) was searched under the key words "diabetic foot".
      Publications of the last three years (2012 to 2014) were extracted. RESULTS: For
      patients with diabetic feet, both endovascular (ER) and open (OR)
      revascularisation techniques are possible. There are not sufficient data to
      demonstrate whether open bypass surgery or endovascular interventions are more
      effective in these patients. However, registries show that ER has now in terms of
      quantity become the preferred method. Angiosome-targeted revascularisation has to
      be considered in these situations. For the local treatment of a diabetic foot
      ulcer a variety of dressings are available, the evidence for their recommendation
      is low. Dressing cost and the wound management properties, e.g. exudate
      management therefore can influence the choice of dressing. There is no evidence
      that more expensive dressings as compared to basic dressings offer advantages in
      terms of healing. In plantar diabetic foot ulcers, non-removable off-loading
      devices regardless of type are more likely to result in ulcer healing than
      removable off-loading devices, presumably, because patient compliance with off
      loading is facilitated. Meaningful pressure-relieving interventions for treating
      diabetic foot ulcers also include Achilles tendon lengthening, a plantar fascia
      release and percutaneous flexor tenotomy. The value of a standardised treatment
      protocol carried out by a specialist team could be proven in large registries
      based on decreasing amputation rates. CONCLUSION: This survey reveals a
      significant disparity between the large number of treatment recommendations and
      their evidence. For the future, therefore it is imperative to implement
      nationwide register surveys with respect to treatment and outcome of these
      patients.

PMID- 25874474
TI  - Constipation in Specialized Palliative Care: Prevalence, Definition, and Patient
      Perceived Symptom Distress.
AB  - BACKGROUND: The prevalence of constipation among patients in palliative care has
      varied in prior research, from 18% to 90%, depending on study factors.
      OBJECTIVES: The aim of this study was to describe and explore the prevalence and
      symptom distress of constipation, using different definitions of constipation, in
      patients admitted to specialized palliative care settings. METHODS: Data was
      collected in a cross-sectional survey from 485 patients in 38 palliative care
      units in Sweden. Variables were analyzed using logistic regression and summarized
      as odds ratio (OR). RESULTS: The prevalence of constipation varied between 7% and
      43%, depending on the definition used. Two constipation groups were found: (1)
      medical constipation group (MCG): <=3 defecations/week, n=114 (23%) and (2)
      perceived constipation group (PCG): patients with a perception of being
      constipated in the last two weeks, n=171 (35%). Three subgroups emerged: patients
      with (1) only medical constipation (7%), (2) only perceived constipation (19%),
      and (3) both medical and perceived constipation (16%). There were no differences
      in symptom severity between groups; 71% of all constipated patients had severe
      constipation. CONCLUSIONS: The prevalence of constipation may differ, depending
      on the definition used and how constipation is assessed. In this study we found
      two main groups and three subgroups, analyzed from the definitions of frequency
      of bowel movements and experience of being constipated. To be able to identify
      constipation, the patients' definition has to be further explored and assessed.

PMID- 25874475
TI  - Cell-type specific photoreceptors and light signaling pathways in the
      multicellular green alga Volvox carteri and their potential role in cellular
      differentiation.
AB  - The formation of multicellular organisms requires genetically predefined
      signaling pathways in various cell types. Besides differences in size, energy
      balance and life time, cell types should be enable to modulate appropriate
      developmental and adaptive responses in ever-changing surrounding environment.
      One of the most important environmental cues is light which regulates a variety
      of physiological and cellular processes. During evolution, diverse light
      sensitive proteins, so-called photoreceptors, and corresponding signaling
      pathways have evolved, in almost all kingdoms of life, to monitor light
      continuously and adjust their growth and development accordingly. However,
      considering the fact that different cell types should be enable to trigger
      distinct light signaling pathways according to their needs, cell-type specific
      light signaling pathways are required to guarantee cell type-matched modulation
      of cellular and developmental processes in response to different light signals.
      The multicellular green alga Volvox carteri, which has only 2 cell types with
      clear division of labor, possesses cell-type specific photoreceptors and light
      signaling pathways which allow differential regulation of genes involved in
      various cellular and metabolic pathways in response to environmental light. The
      existence of cell-type specific light signaling pathways in multicellular
      organism like Volvox reflects an early development of cell-type specific
      signaling mechanisms during evolution to ensure maintenance of differentiation.

PMID- 25874476
TI  - The economic burden of childhood invasive pneumococcal diseases and pneumonia in
      Taiwan: Implications for a pneumococcal vaccination program.
AB  - Invasive pneumococcal disease (IPD) and pneumonia are the major causes of
      morbidity and deaths in children in the world. The management of IPD and
      pneumonia is an important economic burden on healthcare systems and families. The
      aim of this study was to assess the economic burden of IPD and pneumonia among
      younger children in Taiwan. We used a cost-illness approach to identify the cost
      categories for analysis in this study according to various perspectives. We
      obtained data of admission, outpatient, and emergency department visit data from
      the National Health Insurance Research (NHIR) database for children <5 y of age
      between January 2008 and December 2008. A prospective survey was administered to
      the families of patients to obtain detailed personal costs. All costs are
      presented in US dollars and were estimated by extrapolating 2008 cost data to
      2013 price levels. We estimated the number of pneumococcal disease cases that
      were averted if the PCV-13 vaccine had been available in 2008. The total annual
      social and hospital costs for IPD were US $4.3 million and US $926,000,
      respectively. The total annual social and hospital costs for pneumonia were US
      $150 million and US $17 million, respectively. On average, families spent US $653
      or US $218 when their child was diagnosed with IPD or pneumonia, respectively.
      This cost is approximately 27%-81% of the monthly salary of an unskilled worker.
      In conclusion, a safe and effective pediatric pneumococcal vaccine is needed to
      reduce the economic burden caused by pneumococcal infection. 

PMID- 25874478
TI  - Neutrophil CD64 expression - comparison of two different flow cytometry protocols
      on EPICs MCL and the Leuko64(TM) assay on a Celldyn Sapphire haematology
      analyser.
AB  - OBJECTIVE: To evaluate the Trillium Diagnostics Leuko64(TM) assay on Abbott
      Celldyn Sapphire haematology analyser compared to two flow cytometry protocols on
      Beckman Coulter EPICS MCL flow cytometer. MATERIALS AND METHODS: CD64 expression
      on neutrophils was determined by two flow cytometry protocols and by a commercial
      assay on an automatic haematology analyser. The inclusion of study subjects was
      based on elevated procalcitonin (PCT) values, identifying patients where a
      systemic infection was suspected. Healthy blood donors were used as a reference
      group. RESULTS: Statistically significant correlations between the Trillium
      Diagnostics Leuko64(TM) assay and the flow cytometry methods were found when
      measuring neutrophil CD64 expression. CONCLUSIONS: The good correlation between a
      reference method and an automated haematology analyser method for CD64 expression
      on neutrophils supports introduction of the latter assay for routine use as an
      independent biomarker of bacterial infection and inflammation.

PMID- 25874477
TI  - Ryanodine receptor sensitization results in abnormal calcium signaling in airway
      smooth muscle cells.
AB  - Intracellular Ca(2+) dynamics of airway smooth muscle cells (ASMCs) are believed
      to play a major role in airway hyperresponsiveness and remodeling in asthma.
      Prior studies have underscored a prominent role for inositol 1,4,5-triphosphate
      (IP3) receptors in normal agonist-induced Ca(2+) oscillations, whereas ryanodine
      receptors (RyRs) appear to remain closed during such Ca(2+) oscillations, which
      mediate ASMC contraction. Nevertheless, RyRs have been hypothesized to play a
      role in hyperresponsive Ca(2+) signaling. This could be explained by RyRs being
      "sensitized" to open more frequently by certain compounds. We investigate the
      implications of RyR sensitization on Ca(2+) dynamics in ASMC using a combination
      of mathematical modeling and experiments with mouse precision-cut lung slices.
      Caffeine is used to increase the sensitivity of RyRs to cytosolic Ca(2+)
      concentration ([Ca(2+)]i) and sarcoplasmic reticulum Ca(2+) ([Ca(2+)]SR). In
      ASMCs, high caffeine concentrations (>10 mM) induce a sustained elevation of
      [Ca(2+)]i. Our mathematical model accounts for this by the activation of store
      operated Ca(2+) entry that results from a large increase in the RyR sensitivity
      to [Ca(2+)]SR and the associated Ca(2+) release, which leads to a reduction of
      [Ca(2+)]SR. Importantly, our model also predicts that: (1) moderate RyR
      sensitization induces slow Ca(2+) oscillations, a result experimentally confirmed
      with low concentrations of caffeine; and (2) high RyR sensitization suppresses
      fast, agonist-induced Ca(2+) oscillations by inducing substantial store-operated
      Ca(2+) entry and elevated [Ca(2+)]i. These results suggest that RyR sensitization
      could play a role in ASMC proliferation (by inducing slow Ca(2+) oscillations)
      and in airway hyperresponsiveness (by inducing greater mean [Ca(2+)]i for similar
      levels of contractile agonist). 

PMID- 25874479
TI  - Clinical diagnostic Next-Generation sequencing: the case of CFTR carrier
      screening.
AB  - A 23-mutation panel for CFTR carrier screening is recommended to women of
      reproductive age by the American College of Obstetricians and Gynecologists. In
      the present study the optimized efficiency regarding the carrier rate of Next
      Generation sequencing (NGS) technology is compared to the one of limited mutation
      detection panels. A total of 824 consequent cases were subjected to the
      commercial Cystic Fibrosis Genotyping Assay. Some 188 negative samples randomly
      selected from the initial group of probands were further subjected to an extended
      mutation panel characterized by 92% detection rate, as well as to massive
      parallel sequencing. Twenty-two probands subjected to the commercial assay proved
      to carry one mutation included in the ACOG panel (carrier rate 0.0267). The
      latter panels revealed the presence of mutations not included in the ACOG panel
      in four probands, resulting to an increase of carrier rate of 0.0106 in the case
      of in-house panel and an increase of rate of 0.0213 if NGS was used. The above
      data seem to support the implementation of NGS in the routine CFTR carrier
      screening. 

PMID- 25874480
TI  - Evaluation of leptin in subjects with type 2 diabetes mellitus.

PMID- 25874481
TI  - A rare case of Hemoglobin Leiden interfering with the DIFF channel of Sysmex XE
      2100.

PMID- 25874482
TI  - Evaluation of the estimated variables for scaling glomerular filtration rate of
      renal patients: a repeated measures-based method.
AB  - OBJECTIVE: Using a best variable to scale glomerular filtration rate (GFR) is
      important for clinical practice. The variables, estimated by equations regressed
      from a healthy population, are usually used in scaling GFR of renal patients.
      However, because the predicted variables may deviate in renal patients, it is
      necessary to verify whether these variables can be used to reduce the variability
      of GFR of renal patients. This study was designed to use repeated measures
      analyses to identify the best variable for scaling GFR of renal patients.
      METHODS: Patients with non-obstructive renal diseases were enrolled in this
      study. The absolute GFRs of (99m)Tc-DTPA renography (gGFR) and plasma clearance
      (pGFR) were measured. The indices relating to between-subjects variability, such
      as Passing and Bablok regression, intraclass correlation coefficient (ICC) and
      concordance correlation coefficient (CCC) were used to identify the best variable
      from body surface area (BSA), extracellular fluid volume (ECV), lean body mass
      (LBM), total body water (TBW), body mass index (BMI), and metabolic rate (MR).
      RESULTS: For the scaled indices related to between-subjects variability, ICC and
      CCC identified the same ranking sequence (BMI < LBMB(B; Boer) < LBMJ(J; James) <
      TBW < ECVB(B; Bird) < ECVS(S; Silva) < BSA < MR). In the Passing and Bablok
      regression, the ratio of residual standard deviation to pooled standard deviation
      (RSD/PSD) produced the same ranking sequence as that identified by ICC and CCC.
      CONCLUSION: The estimated metabolic rate can explain most between-subjects
      variability of GFR, and seems to be the best variable for scaling GFR of renal
      patients.

PMID- 25874485
TI  - High CHMP4B expression is associated with accelerated cell proliferation and
      resistance to doxorubicin in hepatocellular carcinoma.
AB  - Charged multivesicular body protein 4B (CHMP4B), a subunit of the endosomal
      sorting complex required for transport (ESCRT)-III complex, plays an important
      part in cytokinetic membrane abscission and the late stage of mitotic cell
      division. In this study, we explored the prognostic significance of CHMP4B in
      human hepatocellular carcinoma (HCC) and its impact on the physiology of HCC
      cells. Western blot and immunohistochemistrical analyses showed that CHMP4B was
      significantly upregulated in HCC tissues, compared with adjacent non-tumorous
      tissues. Meanwhile, clinicopathological analysis revealed that high CHMP4B
      expression was correlated with multiple clinicopathological variables, including
      AFP, cirrhosis, AJCC stage, Ki-67 expression, and poor prognosis. More
      importantly, univariate and multivariate survival analyses demonstrated that
      CHMP4B served as an independent prognostic factor for survival of HCC patients.
      Using HCC cell cultures, we found that the expression of CHMP4B was progressively
      upregulated after the release from serum starvation. To verify whether CHMP4B
      could regulate the proliferation of HCC cells, CHMP4B was knocked down through
      the transfection of CHMP4B-siRNA oligos. Flow cytometry and CCK-8 assays
      indicated that interference of CHMP4B led to cell cycle arrest and proliferative
      impairment of HCC cells. Additionally, depletion of CHMP4B expression could
      increase the sensitivity to doxorubicin in HepG2 and Huh7 cells. Taken together,
      our results implied that CHMP4B could be a promising prognostic biomarker as well
      as a potential therapeutic target of HCC. 

PMID- 25874486
TI  - Knockdown of Aurora-B alters osteosarcoma cell malignant phenotype via decreasing
      phosphorylation of VCP and NF-kappaB signaling.
AB  - The aim of this study is to investigate the effects of inhibiting Aurora-B on
      osteosarcoma (OS) cell malignant phenotype, phosphorylation of valosin-containing
      protein (VCP), and the activity of NF-kappaB signaling in vitro. The expressions
      of Aurora-B and p-VCP proteins were detected by immunohistochemistry in 24 OS
      tissues, and the relationship between Aurora-B and p-VCP was investigated. The
      results showed that there was a positive correlation between Aurora-B and p-VCP
      proteins. The expression of Aurora-B in human OS cell lines U2-OS and HOS cells
      was inhibited by specific short hairpin RNA (shRNA) lentivirus (AURKB-shRNA
      lentivirus, Lv-shAURKB) which targeted Aurora-B. The results showed that the
      phosphorylation of VCP, the activity of NF-kappaB signaling pathway and the
      malignant phenotype of OS cells were all suppressed by knockdown of Aurora-B. It
      indicated that the inhibition of Aurora-B alters OS cells malignant phenotype by
      downregulating phosphorylation of VCP and activating of the NF-kappaB signaling
      pathway in vitro. 

PMID- 25874487
TI  - Neoadjuvant chemotherapy followed by radical surgery as an alternative treatment
      to concurrent chemoradiotherapy for young premenopausal patients with FIGO stage
      IIB squamous cervical carcinoma.
AB  - Concurrent chemoradiotherapy (cCRT) is the standard of care for International
      Federation of Gynecology and Obstetrics (FIGO) stage IIB squamous cervical
      carcinoma (SCC). However, an increasing number of young patients with stage IIB
      SCC are concerned with preserving their ovarian and vaginal functions during
      treatment. This retrospective study aimed to compare clinical prognosis between
      young patients with stage IIB SCC treated with neoadjuvant chemotherapy (NACT)
      followed by radical surgery (RS) and those treated with cCRT. Medical records of
      244 premenopausal patients aged <45 years with FIGO stage IIB SCC treated with
      NACT+RS and cCRT between February 2007 and June 2009 were reviewed. All these
      patients completed the treatment plan. NACT+RS resulted in recurrence (35.9
      versus 41.8 %, P = 0.350), progression-free survival (PFS) rate (log-rank, P =
      0.456), and overall survival (OS) rate (log-rank, P = 0.637) comparable to cCRT.
      Compared with cCRT, NACT+RS did not show a significant statistical difference in
      clinical prognosis of premenopausal patients with stage IIB SCC. Therefore,
      NACT+RS may be considered as an alternative treatment for the young patients who
      are concerned with preserving endocrine function, and this alternative treatment
      may also be administered when radiotherapy is unavailable.

PMID- 25874488
TI  - MicroRNA-15a induces cell apoptosis and inhibits metastasis by targeting BCL2L2
      in non-small cell lung cancer.
AB  - MicroRNAs (miRNAs) play a critical role in cancer development and progression.
      Aberrant expression of miR-15a has recently been reported in several cancers, but
      its role in non-small cell lung cancer (NSCLC) still remains obscure. We
      investigated the effects of miR-15a on proliferation, apoptosis, and metastasis
      in A549 cells. Eighteen paired NSCLC and adjacent non-tumor lung tissues were
      surgically removed and immediately snap frozen until total RNA was extracted and
      confirmed by two independent pathologists. The targets of miR-15a were predicted
      by bioinformatics tools. RNA isolation and quantitative real-time PCR (qRT-PCR),
      Western blot analysis, cell proliferation assay, cell cycle analysis, cell
      apoptosis assay, and migration and invasion assays were done. The wild type (WT)
      or mutant type (MT) 3'-untranslated region (UTR) vectors were co-transfected with
      miR-15a or negative control into A549 cells, and after 24 h of transfection,
      luciferase activity was measured using the Dual-Glo luciferase assay kit.
      Statistical analysis was performed using SPSS 13.0 software (SPSS, Chicago, IL,
      USA). P values of less than 0.05 were considered statistically significant. miR
      15a was significantly downregulated in NSCLC than in adjacent non-cancerous
      tissues. miR-15a overexpression remarkably inhibited cell viability, invasion,
      and migration and promoted the apoptosis of NSCLC cells. Additionally, inhibition
      of miR-15a expression had the opposite effects on tumor progression, while cell
      cycle remained unaltered. Furthermore, we identified that BCL2L2 was a target of
      miR-15a and negatively regulated by miR-15a at the translational level. miR-15a
      acts as a tumor suppressor in NSCLC by directly targeting BCL2L2 and may serve as
      a potential diagnostic biomarker and therapeutic target for NSCLC.

PMID- 25874489
TI  - Association between ADH1B and ADH1C polymorphisms and the risk of head and neck
      squamous cell carcinoma.
AB  - Alcohol consumption is one of the major risk factors for head and neck squamous
      cell carcinoma (HNSCC), and the alcohol dehydrogenase (ADH) family proteins are
      key enzymes in ethanol metabolism. We examined the associations between single
      nucleotide polymorphisms (SNPs) of ADH1B and ADH1C and the risk of HNSCC. We
      analyzed six SNPS of ADH1B, namely -992C > G, -957C > A, +3170A>G, +3377G>T,
      +3491G>A, and +13543A>G, and five SNPs of ADH1C, namely -1064C>T, -325G>C,
      +5702A>G, +7462T>C, and +13044A>G, in 260 Korean HNSCC patients and 330 controls,
      using single base extension and the TaqMan assay. The odds ratios (ORs) and 95 %
      confidence intervals (95 % CIs) of the CG and GG genotypes of ADH1B -992C>G, the
      AA genotype of -957C>A, the GG genotype of +3170A>G, the GA genotype of +3491G>A,
      and +13543A>G were 0.51 (0.32-0.82), 0.63 (0.42-0.94), 1.84 (1.13-2.99), 1.77
      (1.15-2.73), 2.34 (1.44-3.79), and 2.21 (1.23-3.95), respectively. The ORs of
      ADH1C +13044A>G were 1.94 (1.01-3.71) and 1.97 (1.05-3.71) in the dominant and co
      dominant models, respectively. The ORs of the GC genotype of ADH1C -325G>C and
      the AG genotype of +5702A>G were 2.52 (1.51-4.21) and 2.43 (1.36-4.32),
      respectively. ADH1B +3170A>G and ADH1C +13044A>G were in strong linkage
      disequilibrium with the other SNPs of ADH1B and ADH1C, respectively. There were
      gene-environment interactions between ADH1B +3170A>G and ADH1C +13044A>G and
      alcohol consumption and smoking. ADH1B +3170A>G and ADH1C +13044A>G SNPs are
      associated with an increased risk of HNSCC, and they could be used as biomarkers
      for the high-risk group of HNSCC in Koreans.

PMID- 25874490
TI  - Protein kinase D2 silencing reduced motility of doxorubicin-resistant MCF7 cells.
AB  - Success of chemotherapy is generally impaired by multidrug resistance, intrinsic
      resistance, or acquired resistance to functionally and structurally irrelevant
      drugs. Multidrug resistance emerges via distinct mechanisms: increased drug
      export, decreased drug internalization, dysfunctional apoptotic machinery,
      increased DNA damage repair, altered cell cycle regulation, and increased drug
      detoxification. Several reports demonstrated that multidrug resistance is a
      multifaceted problem such that multidrug resistance correlates with increased
      aggressiveness and metastatic potential. Here, we tested the involvement of
      protein kinase D2, a serine/threonine kinase that was previously implicated in
      proliferation, drug resistance, and motility in doxorubicin-resistant MCF7
      (MCF7/DOX) cell line, which served as an in vitro model for drug resistance and
      invasiveness. We showed that basal level activity of protein kinase D2 (PKD2) was
      higher in MCF7/DOX cells than parental MCF7 cells. To elucidate the roles of PKD2
      MCF7/DOX, PKD2 expression was reduced via small interfering RNA (siRNA)-mediated
      knockdown. Results showed that acquired resistance of MCF7/DOX to doxorubicin was
      not affected by PKD2 silencing, while motility of MCF7/DOX cells was reduced. The
      results implied that PKD2 silencing might inhibit migration of MCF7/DOX cells
      without affecting chemoresistance significantly.

PMID- 25874491
TI  - Divergent expression patterns of SATB1 mRNA and SATB1 protein in colorectal
      cancer and normal tissues.
AB  - Special AT-rich sequence-binding protein 1 (SATB1) is a 'genome organizer,' and
      it has been proposed as a factor that affects the development and progression of
      various human neoplasms, including colorectal cancer (CRC). This study aimed to
      compare SATB1 expression in a group of CRC patients and healthy subjects at the
      mRNA and protein levels. We collected paired tumor tissue and unchanged mucosa of
      the large intestine from 102 CRC patients as well as 53 biopsies of normal colon
      mucosa obtained from healthy patients during screening colonoscopy. Tissue
      samples were quantified for SATB1 mRNA by quantitative PCR, while SATB1 protein
      expression was determined by Western blotting and immunohistochemistry. SATB1
      mRNA level in tumor tissues was over twofolds lower than in samples of
      corresponding unchanged tissues and fourfolds lower than in biopsies of healthy
      colon mucosa. Western blotting analysis revealed that SATB1 protein content in
      tumor and unchanged tissues of CRC patients was over sixfold and fivefolds higher
      than in biopsies of healthy colon mucosa, respectively. Immunohistochemical
      staining demonstrated higher nuclear and cytoplasmic SATB1 reactivity in the
      tumor tissue compared to unchanged mucosa of CRC patients. Despite these
      differences, SATB1 mRNA, protein, and immunoreactivity levels did not correlate
      with patients' clinicopathological data and their overall survival, but the
      latter analysis was limited by a relatively short period of follow-up. In
      conclusion, we suggest that some as yet unidentified posttranscriptional
      mechanisms that regulate SATB1 expression may be altered in the CRC tissue.

PMID- 25874492
TI  - Clinical significance of Sam68 expression in endometrial carcinoma.
AB  - Sam68 (Src-associated in mitosis of 68 kDa) is a substrate for tyrosine kinase c
      Src during mitosis. The nuclear protein level has been found to be associated
      with progression and prognosis in various human malignant tumors. The aim of this
      study is to investigate the clinical value of Sam68 in endometrial carcinoma
      (EC). Sam68 expression was confirmed by real-time PCR, Western blot, and
      immunofluorescent assay in primary normal endometrial epithelial cells,
      endometrial carcinoma cell lines, as well as seven pairs of EC and matched
      adjacent noncancerous endometrial tissues. Moreover, the protein level of Sam68
      was evaluated by immunohistochemistry in a cohort of surgical specimens derived
      from 131 patients including primary endometrial carcinoma (n = 95), endometrial
      atypical hyperplasia (precancerous lesions, n = 26), and normal endometria (n =
      10). In endometrial cancer cell lines, RNA interfering approach was employed to
      downregulate Sam68 expression to determine its role in proliferation.
      Clinicopathological relevance and prognostic associations were examined by
      statistical analyses. Compared with normal endometrial and endometrial atypical
      hyperplasia tissues, Sam68 significantly elevated in endometrial cancer samples
      (P < 0.01), which was negative or low in 37 cases (38.9 %) and high in 58 cases
      (61.1 %). The high expression of Sam68 was associated with histological grade (P
      < 0.001), FIGO stage (P = 0.039), and myometrial invasion (P = 0.002). Kaplan
      Meier analysis demonstrated that overexpression of Sam68 correlated with shorter
      overall survival. It is confirmed by univariate and multivariate analysis (P <
      0.001 and P = 0.048, respectively). Additionally, we found that Sam68 was highly
      expressed at both the transcriptional and translational levels in endometrial
      cancer cell lines (Ishikawa, HEC-1B, AN3CA, KLE, and RL95-2) and siRNA knockdown
      of Sam68 remarkably inhibited cellular proliferation in in vitro models. Sam68
      may be useful prognostic marker for EC, and it plays an important role in
      promoting the cellular proliferation. Further investigation of Sam68 as a
      potential therapeutic target for EC patients could be of interest.

PMID- 25874493
TI  - MET is a predictive factor for late recurrence but not for overall survival of
      early stage hepatocellular carcinoma.
AB  - The MET and RON receptors are tyrosine kinases that form a non-covalent complex
      on the cell surface that functions in several steps of tumor progression. The
      purpose of this study was to determine the clinical significance of MET and RON
      expression on long-term survival and recurrence after curative resection in a
      large cohort of hepatocellular carcinoma (HCC) patients. We performed
      immunohistochemical analyses on microarrays of the tumors using antibodies
      against MET and RON. We evaluated the prognostic value of biomarker expression
      using Cox regression and the Kaplan-Meier method in 490 HCC patients. MET
      positive patients had higher overall recurrence rates than MET-negative patients
      (P = 0.041); however, MET positivity was not associated with overall survival
      (OS) (P =  .249). RON was not associated with overall recurrence rates and OS.
      MET was independently associated with late but not early phase recurrence.
      Particularly, the prognostic significance of MET is limited in early stage
      disease. MET+/RON+ patients had higher overall recurrence rates than those with
      the other expression patterns (P = 0.071), although the result did not reach
      statistical significance. Immunohistological activation of MET expression has no
      prognostic significance for OS in patients with HCC. However, MET positivity was
      correlated with late recurrence after HCC resection in early stage disease.

PMID- 25874494
TI  - Curcumin suppresses lymphatic vessel density in an in vivo human gastric cancer
      model.
AB  - This study aimed to assess the effects of curcumin on lymphatic vessel density
      (LVD) in an in vivo model of gastric cancer using the gastric cancer cell line,
      SGC-7901. Gastric tumor-bearing nude mice were treated with saline or 40, 80, or
      160 mg kg(-1) day(-1) curcumin for 8 weeks. The results indicated that the tumor
      volumes were significantly lower in mice treated with 80 and 160 mg kg(-1) day(
      1) curcumin as compared with that of the control group (both P < 0.001). In
      addition, both 80 and 160 mg kg(-1) day(-1) curcumin significantly reduced LVD
      (both P < 0.01). Although immunohistochemical analysis showed that curcumin did
      not significantly alter the expression of prospero homeobox 1 (Prox-1),
      podoplanin, and vascular endothelial growth factor receptor 3 (VEGFR-3), 160 mg
      kg(-1) day(-1) curcumin significantly decreased the expression of Prox-1,
      podoplanin, and VEGFR-3 levels as detected by Western blot analysis (P <= 0.03).
      Downregulation of lymphatic vessel endothelial receptor 1 (LYVE-1), Prox-1,
      podoplanin, and VEGFR-3 mRNA expression by curcumin was also detected (all P <
      0.05). Furthermore, the apoptosis rates of tumor cells increased with curcumin in
      a concentration-dependent manner (all P < 0.001). Thus, curcumin may inhibit
      gastric cancer lymph node metastasis. Our findings provide theoretical evidence
      and an experimental basis for further analysis of the clinical application of
      curcumin in the therapy of gastric cancer.

PMID- 25874495
TI  - Long noncoding RNAs POLR2E rs3787016 C/T and HULC rs7763881 A/C polymorphisms are
      associated with decreased risk of esophageal cancer.
AB  - Worldwide, rates of esophageal cancer have been keeping highly in recent decades.
      Genetic variants in multiple cellular pathways might play an important role in
      altering risk of esophageal carcinoma. In this study, long noncoding RNAs
      (lncRNAs) functional single nucleotide polymorphisms (SNPs) were investigated in
      Chinese Han populations. We have genotyped the ANRIL rs2151280 T/C, POLR2E
      rs3787016 C/T, and HULC rs7763881 A/C SNPs in 380 esophageal squamous cell
      carcinoma (ESCC) cases and 380 cancer-free controls. POLR2E rs3787016 C/T was
      associated with a significantly decreased risk for ESCC (CT vs. CC: OR 0.62, 95 %
      CI 0.44-0.87, P = 0.005; adjusted OR 0.62, 95 % CI 0.44-0.87, P = 0.005). The
      other SNP, HULC rs7763881, also showed a suggestive association (AC vs. AA: OR
      0.70, 95 % CI 0.50-0.98, P = 0.037; adjusted OR 0.69, 95 % CI 0.49-0.97, P =
      0.031). ANRIL rs2151280 T/C SNP was not associated with risk of ESCC. In the
      future, larger studies with other ethnic populations, tissue-specific biological
      characterization, and detailed individual information should be undertaken to
      validate current findings.

PMID- 25874496
TI  - MicroRNA-1 (miR-1) inhibits gastric cancer cell proliferation and migration by
      targeting MET.
AB  - MicroRNAs (miRs) are short endogenous non-coding RNAs that act as
      posttranscriptional regulatory factors of gene expression. Downregulation of miR
      1 has been reported in gastric cancer; however, the mechanisms underlying its
      functions via target genes in gastric cancer remain largely unknown. The purpose
      of this study was to investigate the mechanism by which miR-1 inhibits gastric
      cancer cell proliferation and migration. The effects of miR-1 on gastric cancer
      cell proliferation and migration were determined by MTT and wound-healing assays.
      Cell protein expression of the miR-1 target gene MET was analyzed by Western
      blotting. Finally, MET expression was evaluated by immunohistochemistry in a
      stomach tumor tissue microarray (TMA). Ectopic expression of miR-1 inhibited
      proliferation and migration in both AGS and SGC-7901 gastric cancer cell lines.
      miR-1 directly targets the MET gene and downregulates its expression. MET siRNA
      also inhibited proliferation and migration in both cell lines.
      Immunohistochemistry revealed significantly higher MET expression levels in
      gastric cancer tissues compared with matched adjacent non-cancer tissues. These
      findings indicate that the miR-1/MET pathway is a potential therapeutic target
      due to its crucial role in gastric cancer cell proliferation and migration.

PMID- 25874498
TI  - A Aconitum coreanum polysaccharide fraction induces apoptosis of hepatocellular
      carcinoma (HCC) cells via pituitary tumor transforming gene 1 (PTTG1)-mediated
      suppression of the P13K/Akt and activation of p38 MAPK signaling pathway and
      displays antitumor activity in vivo.
AB  - In this study, we observed that a Aconitum coreanum polysaccharide (CACP)
      exhibited an effective inhibitory effect on H22 cell growth in vitro and in vivo
      via the induction of apoptosis. Further, quantitative real-time polymerase chain
      reaction (qRT-PCR) and Western blotting assays revealed that the expression of
      pituitary tumor transforming gene 1 (PTTG1), one proto-oncogene, was evidently
      suppressed in both transcript and protein levels in H22 cell model or mice after
      CACP treatment. Particularly, CACP (40 MUg/ml) treatment or transfection with
      PTTG1 small interfering RNA (siRNA) could greatly reduce the phosphorylation of
      Akt (p-Akt) but increase phospho-p38 mitogen-activated protein kinase (p-p38
      MARK) protein levels in H22 cells as compared with vehicle-treated cells.
      Likewise, following treatment of H22-tumor-bearing mice with CACP (100 mg/kg),
      doxorubicin (DOX, 3 mg/kg), and their combination, tumor tissues showed an
      attenuated p-Akt protein expression, but a striking p-p38 MARK level when
      compared with those in model mice. Taken together, we demonstrated here the
      inhibitory effect of CACP on the growth of H22 cells in vitro and in vivo, which
      may be through, at least partly, repression of PTTG1 and then followed by the
      inactivation of P13/Akt and activation of p38 MARK signaling pathways. These
      findings offered a novel approach for the treatment of hepatocellular carcinoma
      (HCC) in the future. 

PMID- 25874497
TI  - Killing of cancer cells through the use of eukaryotic expression vectors
      harbouring genes encoding nucleases and ribonuclease inhibitor.
AB  - Cancer gene therapy vectors are promising tools for killing cancer cells with the
      purpose of eradicating malignant tumours entirely. Different delivery methods of
      vectors into the cancer cells, including both non-viral and viral, as well as
      promoters for the targeted expression of genes encoding anticancer proteins were
      developed for effective and selective killing of cancer cells without harming
      healthy cells. Many vectors have been created to kill cancer cells, and some
      vectors suppress malignant tumours with high efficiency. This review is focused
      on vectors bearing genes for nucleases such as deoxyribonucleases (caspase
      activated DNase, deoxyribonuclease I-like 3, endonuclease G) and ribonucleases
      (human polynucleotide phosphorylase, ribonuclease L, alpha-sarcin, barnase), as
      well as vectors harbouring gene encoding ribonuclease inhibitor. The data
      concerning the functionality and the efficacy of such vectors are presented. 

PMID- 25874500
TI  - Design of an optimum computer vision-based automatic abalone (Haliotis discus
      hannai) grading algorithm.
AB  - An automatic abalone grading algorithm that estimates abalone weights on the
      basis of computer vision using 2D images is developed and tested. The algorithm
      overcomes the problems experienced by conventional abalone grading methods that
      utilize manual sorting and mechanical automatic grading. To design an optimal
      algorithm, a regression formula and R(2) value were investigated by performing a
      regression analysis for each of total length, body width, thickness, view area,
      and actual volume against abalone weights. The R(2) value between the actual
      volume and abalone weight was 0.999, showing a relatively high correlation. As a
      result, to easily estimate the actual volumes of abalones based on computer
      vision, the volumes were calculated under the assumption that abalone shapes are
      half-oblate ellipsoids, and a regression formula was derived to estimate the
      volumes of abalones through linear regression analysis between the calculated and
      actual volumes. The final automatic abalone grading algorithm is designed using
      the abalone volume estimation regression formula derived from test results, and
      the actual volumes and abalone weights regression formula. In the range of
      abalones weighting from 16.51 to 128.01 g, the results of evaluation of the
      performance of algorithm via cross-validation indicate root mean square and worst
      case prediction errors of are 2.8 and +/-8 g, respectively. 

PMID- 25874499
TI  - The role of hypoxia-inducible factor-1alpha in radiation-induced autophagic cell
      death in breast cancer cells.
AB  - Hypoxia-inducible factor-1alpha (HIF-1alpha) is a major effector in cell survival
      response to hypoxia, while the roles of HIF-1alpha in radiation-induced autophagy
      are still unclear in breast cancer cells. Human breast cancer carcinoma MCF-7
      cells were stably transfected with pSUPER-shRNA against human HIF-1alpha or a
      scrambled sequence with no homology to mammalian genes, named as pSUPER-HIF
      1alpha and pSUPER-SC, respectively. Cell Counting Kit-8 (CCK-8) assay and colony
      formation assay were used to detect cell viability, Western blot was used to
      detect protein expression, monodansylcadaverine (MDC) staining was used to
      analyze autophagy, and Hoechts/PI staining was used to assess apoptosis. Ionizing
      radiation (IR) and cobalt chloride (CoCl2) could induce HIF-1alpha expression and
      increase the microtubule-associated protein 1 light chain 3 (MAPLC3)-II/MAPLC3-I
      ratio, especially in radiation + CoCl2 group. After the silencing of HIF-1alpha,
      the radiosensitivity of MCF-7 cells increased and the autophagy level decreased
      in response to DNA damage induced by ionizing radiation, but there was no
      influence on IR-induced apoptosis. HIF-1alpha silencing also increased the
      expression of phospho-Akt, mTOR, and P70S6K and activated the mTOR signals
      significantly. Hypoxia can induce autophagy and also improve the IR-induced
      autophagy via the suppression of Akt/mTOR/P70S6K pathway, which consequently lead
      to radioresistance.

PMID- 25874501
TI  - Car drivers with dementia: Different complications due to different etiologies?
AB  - OBJECTIVE: Older drivers with dementia are an at-risk group for unsafe driving.
      However, dementia refers to various etiologies and the question is whether
      dementias of different etiology have similar effects on driving ability. METHODS:
      The literature on the effects of dementia of various etiologies on driving
      ability is reviewed. Studies addressing dementia etiologies and driving were
      identified through PubMed, PsychINFO, and Google Scholar. RESULTS AND
      CONCLUSIONS: Early symptoms and prognoses differ between dementias of different
      etiology. Therefore, different etiologies may represent different likelihoods
      with regard to fitness to drive. Moreover, dementia etiologies could indicate the
      type of driving problems that can be expected to occur. However, there is a great
      lack of data and knowledge about the effects of almost all etiologies of dementia
      on driving. One could hypothesize that patients with Alzheimer's disease may well
      suffer from strategic difficulties such as finding a route, whereas patients with
      frontotemporal dementia are more inclined to make tactical-level errors because
      of impaired hazard perception. Patients with other dementia etiologies involving
      motor symptoms may suffer from problems on the operational level. Still, the
      effects of various etiologies of dementias on driving have thus far not been
      studied thoroughly. For the detection of driving difficulties in patients with
      dementia, structured interviews with patients but also their family members
      appear crucial. Neuropsychological assessment could support the identification of
      cognitive impairments. The impact of such impairments on driving could also be
      investigated in a driving simulator. In a driving simulator, strengths and
      weaknesses in driving behavior can be observed. With this knowledge, patients can
      be advised appropriately about their fitness to drive and options for support in
      driving (e.g., compensation techniques, car adaptations). However, as long as no
      valid, reliable, and widely accepted test battery is available for the assessment
      of fitness to drive, costly on-road test rides are inevitable. The development of
      a fitness-to-drive test battery for patients with dementia could provide an
      alternative for these on-road test rides, on condition that differences between
      dementia etiologies are taken into consideration.

PMID- 25874502
TI  - N3 and O2 protonated tautomeric conformations of 2'-deoxycytidine and cytidine
      coexist in the gas phase.
AB  - Infrared multiple photon dissociation action spectra of the protonated forms of
      the cytidyl nucleosides, 2'-deoxycytidine, [dCyd+H](+), and cytidine, [Cyd+H](+),
      are acquired over the IR fingerprint and hydrogen-stretching regions. Electronic
      structure calculations are performed at the B3LYP/6-311+G(d,p) level to determine
      the stable low-energy tautomeric conformations of these species generated upon
      electrospray ionization (ESI) and to generate the linear IR absorption spectra of
      these protonated nucleosides. Comparison between the experimental and theoretical
      spectra allows the tautomeric conformations of [dCyd+H](+) and [Cyd+H](+)
      populated by ESI to be determined. B3LYP predicts N3 as the preferred protonation
      site for both [dCyd+H](+) and [Cyd+H](+), whereas MP2 suggests that protonation
      at O2 is more favorable. The 2'-hydroxyl substituent does not significantly alter
      the structures of the B3LYP N3 and MP2 O2 protonated ground tautomeric
      conformations of [dCyd+H](+) vs [Cyd+H](+). [dCyd+H](+) and [Cyd+H](+) exhibit
      very similar spectral signatures in both regions. Nonetheless, the 2'-hydroxyl
      does affect the relative intensities of the IRMPD bands of [dCyd+H](+) vs
      [Cyd+H](+). The spectral features observed in the hydrogen-stretching region
      complement those of the fingerprint region and allow the N3 and O2 protonated
      tautomeric conformations to be readily distinguished. Comparison between the
      measured and computed spectra indicates that both N3 and O2 protonated tautomeric
      conformations coexist in the experiments, and the populations are dominated by
      the most stable N3 and O2 protonated tautomeric conformations. Least-squares
      fitting of the IRMPD spectra to the IR spectra for these most stable conformers
      suggests relative populations of ~55% N3 vs 45% O2 protonated conformers of
      [dCyd+H](+), whereas ~47% N3 vs 53% O2 protonated conformers of [Cyd+H](+). This
      change in the preferred site of protonation indicates that the 2'-hydroxyl
      substituent plays an important role in controlling the reactivity of the cytidyl
      nucleosides. 

PMID- 25874503
TI  - Biocompatible gold nanorods: one-step surface functionalization, highly colloidal
      stability, and low cytotoxicity.
AB  - The conjugation of gold nanorods (AuNRs) with polyethylene glycol (PEG) is one of
      the most effective ways to reduce their cytotoxicity arising from the
      cetyltrimethylammonium bromide (CTAB) and silver ions used in their synthesis.
      However, typical PEGylation occurs only at the tips of the AuNRs, producing
      partially modified AuNRs. To address this issue, we have developed a novel,
      facile, one-step surface functionalization method that involves the use of Tween
      20 to stabilize AuNRs, bis(p-sulfonatophenyl)phenylphosphine (BSPP) to activate
      the AuNR surface for the subsequent PEGylation, and NaCl to etch silver from the
      AuNRs. This method allows for the complete removal of the surface-bound CTAB and
      the most active surface silver from the AuNRs. The produced AuNRs showed far
      lower toxicity than other methods to PEGylate AuNRs, with no apparent toxicity
      when their concentration is lower than 5 MUg/mL. Even at a high concentration of
      80 MUg/mL, their cell viability is still four times higher than that of the tip
      modified AuNRs. 

PMID- 25874504
TI  - Metagenomic analysis for the microbial consortium of anaerobic CO oxidizers.
AB  - Metagenomics analysis has been applied to identify the dominant anaerobic
      microbial consortium of the carbon monoxide (CO) oxidizers in anaerobic sludge.
      Reads from the hypervariable V6 region in the bacterial 16s rDNA were aligned and
      finally clustered into operational taxonomic units (OTUs). The OTUs from
      different stages in anaerobic CO condition were classified. Alphaproteobacteria,
      clostridia, betaproteobacteria and actinobacteria were the most abundant groups,
      while alphaproteobacteria, betaproteobacteria and actinobacteria were variable
      groups. CO consumption and production efficiency of the microbial consortium were
      studied. Semi-continuous trials showed that these anaerobic CO oxidizers formed a
      stable microbial community, and the CO conversion rate was at over 84%, with the
      highest CO consumption activity of 28.9 mmol CO/g VSS?day and methane production
      activity at 7.6 mmol CH4 /g VSS?day during six cycles.

PMID- 25874505
TI  - Synthesis of SF5-Substituted Tetrapyrroles, Metalloporphyrins, BODIPYs, and Their
      Dipyrrane Precursors.
AB  - The synthesis of novel pentafluorosulfanyl (SF5)-substituted A4-type porphyrins,
      their corresponding Zn(II)- and Pd(II)-metal complexes, A3-, A2B- and AB2-type
      corroles, BODIPYs, and their dipyrrane precursors was studied utilizing
      commercially available SF5-substituted aryl aldehydes. In addition, the
      functionalization of SF5-substituted tetrapyrroles was investigated by applying
      the concept of the nucleophilic aromatic substitution (S(N)Ar) with alcohols and
      sodium azide onto the pentafluorophenyl moiety of a trans-A2B2-porphyrin and two
      corrole derivatives with a mixed substitution pattern involving the SF5 group.
      This allows a fine-tuning of the properties of these macrocycles through a
      selective and mild introduction of functional groups, giving access to
      multifunctionalized SF5-substituted porphyrinoids. As an example, one
      functionalized corrole was further reacted with an azido-substituted BODIPY via
      the copper(I)-catalyzed 1,3-dipolar cycloaddition yielding the first corrole
      BODIPY heterodimer involving the pentafluorosulfanyl group.

PMID- 25874506
TI  - Systematic review: knowledge and educational needs of patients with irritable
      bowel syndrome.
AB  - Educational programs have been used as a control condition in trials on
      psychological therapies for irritable bowel syndrome (IBS). An optimal control
      condition should have all logistic features of the experimental intervention,
      except the active component, but also have basic therapeutic benefit for the
      patient. The aim of the present study is to systematically determine patients'
      educational needs on the basis of the (mis)conceptions that they have of their
      disease and their reported desire for information to optimize the control
      intervention in IBS research. A systematic review of studies on the knowledge and
      educational needs of IBS patients in terms of their condition was performed.
      Studies published as full text in the English language in peer-reviewed journals
      and that included adult IBS patients diagnosed according to the Manning or Rome
      I, II, or III criteria were selected. Eight studies involving 2132 patients were
      included. When focusing on misconceptions of patients, the most prevalent are
      that IBS is caused by dietary factors, food allergies and intolerance (37-90%),
      heredity (52%), or a lack of digestive enzymes (52%); IBS is a form of colitis
      (43%); and will last a lifetime (31-54%), develop into cancer (15-49%), or
      worsens with age (48%). Patients are 'unhappy' with their level of knowledge or
      feel poorly informed (65%). They want information about the diagnostic process,
      which foods to avoid (63%), causes (62%), coping strategies (59%), new
      medications (55%), course (52%), and the role of psychological factors (51%). IBS
      patients do have a large variety of educational needs. Educational programs
      optimally addressing these needs can be used adequately as a placebo control
      condition in research on psychological interventions. 

PMID- 25874507
TI  - Intrahepatic cholestasis of pregnancy with concomitant hepatitis C virus
      infection, Joan C. Edwards SOM, Marshall University.
AB  - BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is characterized by
      pruritus, otherwise unexplained deranged liver enzyme levels, and elevated levels
      of serum bile acid. ICP has been observed more commonly in hepatitis C virus
      (HCV) infected women than in women with no HCV infection, and some experts
      advocate testing for HCV infection in all patients with ICP. AIMS: The aim of our
      study was to examine the clinical characteristics of pregnant women with ICP and
      HCV infection. METHODS: We reviewed the records of pregnant women between 18 and
      45 years of age over a period of 6 years with an International Classification of
      Diseases, Ninth Revision (ICD-9) diagnosis of HCV infection, ICP, or both. We
      collected demographic, clinical, and financial data on all the patients and
      compared them with and without a diagnosis of ICP. RESULTS: There were 91
      pregnant women with a diagnosis of HCV, and 41 (45%) of these women were
      diagnosed with ICP. HCV-infected patients with ICP had a significantly higher
      median viral load compared with those without ICP (495,000 vs. 8000 copies/ml,
      P<0.001). The median total financial charges spent for the care of ICP patients
      with HCV infection was significantly higher than that spent on ICP patients
      without HCV infection ($12,753.00 vs. $8970.00, P=0.01). CONCLUSION: We found a
      high prevalence of ICP among pregnant women infected with HCV, and those with ICP
      had a higher HCV viral load. Women with suspected ICP should be tested for the
      presence of HCV.

PMID- 25874508
TI  - Occult hepatitis B infection in children with chronic liver disease.
AB  - AIMS: Occult hepatitis B infection (OBI) may adversely affect the outcome of
      patients with chronic liver disease (CLD). There are no data on OBI and CLD in
      children. This study determined the prevalence and effect of OBI in HBsAg
      negative CLD children. MATERIALS AND METHODS: CLD children were prospectively
      evaluated with a demographic, clinical, and investigative proforma. All HBsAg
      negative CLD cases were tested for exposure to hepatitis B (total anti-HBc, anti
      HBs). Serum hepatitis B virus DNA was measured in exposed (total anti-HBc
      positive) patients. RESULTS: A total of 115 HBsAg-negative CLD children (59 boys,
      age 9.0+/-3.6 years) were enrolled. The etiology of CLD was known in 94 cases and
      21 children had cryptogenic CLD. Of these, 45 (39.1%) had evidence of HBV
      exposure (23 total anti-HBc positive, 17 total anti-HBc and anti-HBs positive,
      five only anti-HBs positive without previous vaccination). The anti-HBc-positive
      children had a higher Child's score than the anti-HBc-negative children [11 (5
      13) vs. 7 (5-13); P=0.00]. A total of 4/45 children had seropositive OBI with
      serum HBV DNA of 8, 36, 133, and 156 IU/ml, respectively. The proportion of total
      anti-HBc positivity (8/21 vs. 32/94; P=0.8) and OBI (2/21 vs. 2/94; P=0.1) was
      similar in cryptogenic CLD and known cause CLD. CONCLUSION: Seropositive OBI is
      infrequent in Indian children with CLD. The prevalence is similar in cryptogenic
      and CLD of known etiology.

PMID- 25874509
TI  - Diagnostic performance of collagen IV and laminin for the prediction of fibrosis
      and cirrhosis in chronic hepatitis C patients: a multicenter study.
AB  - BACKGROUND/AIM: To date, liver biopsy has been the gold standard used for the
      assessment of liver fibrosis in patients with chronic hepatitis C. Our aim was to
      evaluate the diagnostic performance of a panel of simple blood markers of liver
      fibrosis and the development a novel score to replace liver biopsy. PATIENTS AND
      METHODS: Liver biochemical profile including transaminases, bilirubin, alkaline
      phosphatase, and albumin, in addition to platelet count, was evaluated using
      standard methods in 305 chronic hepatitis C patients. Serum type IV collagen and
      laminin were assayed using the ELISA technique. Liver biopsies were performed.
      Statistical analyses were carried out by logistic regression and receiver
      operating characteristic curves to assess and compare the diagnostic accuracy of
      blood markers. A stepwise combination algorithm was developed and validated in
      317 additional patients. RESULTS: The Fibrosis Discriminant Score (FDS) was
      developed combining collagen, laminin, aspartate aminotransferase/platelet ratio
      index, and albumin. FDS produced an area under receiver operating characteristic
      curve of 0.831 for significant fibrosis, 0.791 for advanced fibrosis, and 0.881
      for cirrhosis. The FDS was correctly classified in 82% of patients with
      significant fibrosis with 79% sensitivity and 88% specificity at cut-off 0.66 or
      more. Similar results were obtained in a validation study in which, of 317
      patients, liver biopsy could have been avoided in 81%. CONCLUSION: A simple
      fibrosis index can be useful to select hepatitis C virus-infected patients with a
      very low risk of significant fibrosis in whom the protocol of liver biopsies may
      be avoided.

PMID- 25874510
TI  - Comparison of 2 days versus 5 days of octreotide infusion along with endoscopic
      therapy in preventing early rebleed from esophageal varices: a randomized
      clinical study.
AB  - BACKGROUND: Variceal bleeding is a medical emergency with 20% mortality at 6
      weeks. The role of vasoactive agents in achieving hemostasis and preventing
      rebleeding has been well documented. The optimal duration of these agents has not
      been well established. There are no previous studies yielding the exact duration
      of octreotide to be administered to prevent rebleed and mortality from esophageal
      varices. The aim of this study is to evaluate the effect of combination therapy
      (octreotide and endoscopy), the exact duration of octreotide infusion, its cost
      effectiveness, and the outcome in terms of rebleed and mortality. PATIENTS AND
      METHODS: This was a randomized clinical trial including 124 patients with acute
      variceal bleeding who underwent endoscopic therapy; they were assigned randomly
      to 2 days (n=62) and 5 days (n=58) of continuous octreotide infusion (50 MUg/kg).
      Early rebleeding (within 42 days of index bleed according to Baveno IV consensus
      guidelines), transfusion requirement, and mortality were assessed. RESULTS: The
      study had predominantly male patients, average age 47 years. Among the patients
      in the 2-day group, 3 (4.8%) showed early rebleed versus 5 (8.6%) in the 5-day
      group, but the difference was not statistically significant (P>0.05). Among the
      patients in the 2-day group, one patient died after 3 weeks and all the patients
      in the 5-day group survived till 6 weeks on follow-up, and the survival rates
      were comparable (P>0.05). The treatment in the 5-day group was 2.5 times costlier
      than that for the 2-day group as shown by a cost-wise analysis. CONCLUSION: Two
      days of octreotide infusion following endoscopic therapy is sufficient and as
      efficacious as 5 days of infusion in preventing early rebleed, with reasonably
      better cost-effectiveness.

PMID- 25874511
TI  - Impact of cardiac dysfunction on health-related quality of life in cirrhotic
      liver transplant candidates.
AB  - OBJECTIVE: Cardiac dysfunction, in particular left ventricular diastolic
      dysfunction, is common in cirrhosis. We aimed to investigate the impact of
      cardiac dysfunction on health-related quality of life (QoL) in liver cirrhosis.
      MATERIALS AND METHODS: A total of 88 cirrhotic liver transplant candidates with
      an available echocardiogram and ECG completed the Short form-36 (SF-36) and
      Fatigue Impact Scale. In a subgroup of 61 patients, levels of cardiac biomarkers,
      in particular serum N-terminal pro-brain natriuretic peptide, adiponectin, and
      high-sensitive troponin T, were also measured. RESULTS: Although left ventricular
      systolic diameter was related to a lower SF-36 physical component summary,
      neither left ventricular diastolic dysfunction nor any other echocardiographic
      feature was found to be associated with any other SF-36 or Fatigue Impact Scale
      domain (P>0.05 for all). On linear regression analysis after adjustment for
      confounders, a prolonged QTc interval was found to be related to a lower SF-36
      mental component summary score (beta=-9.7, P=0.009) and increased physical
      fatigue (beta=10.5, P=0.004). Neither serum N-terminal pro-brain natriuretic
      peptide, high-sensitivity troponin T, nor adiponectin levels were found to be
      related to QoL (P>0.05 for all). Serum adiponectin levels did not differ among
      patients with versus those without echocardiographic cardiac alterations (P>0.05
      for all). CONCLUSION: A prolonged QTc interval, but not any echocardiographic
      abnormalities or cardiac biomarkers, seems to be predictive of QoL in cirrhosis.

PMID- 25874512
TI  - Whole-liver diffusion-weighted MRI histogram analysis: effect of the presence of
      colorectal hepatic metastases on the remaining liver parenchyma.
AB  - OBJECTIVES: To explore whether whole-liver diffusion-weighted MRI analysis (of
      the apparently normal liver parenchyma) can help differentiate between patients
      with colorectal liver metastasis and controls without liver disease. MATERIALS
      AND METHODS: Ten patients with colorectal liver metastasis and 10 controls with
      no focal/diffuse liver disease underwent liver MRI at 1.5 T including diffusion
      weighted imaging (DWI; b-values 0, 50, 100, 500, 750, 1000). Apparent diffusion
      coefficient (ADC) maps were calculated from the DWI images to carry out
      quantitative diffusion analyses. An experienced reader performed segmentation of
      the apparently nondiseased liver (excluding metastases/focal liver lesions) on
      the ADC maps. Histogram ADC parameters were calculated and compared between the
      patients and the controls. RESULTS: The mean liver ADC was 0.95*10-3 mm2/s for
      the patients versus 1.03*10-3 mm2/s for the controls (P=0.42). The fifth
      percentile of the ADC was significantly lower for the patients compared with the
      controls (0.45 vs. 0.69 10-3 mm2/s, P=0.01). The SD was significantly higher in
      the patient group (0.30 vs. 0.22, P<0.001). Median, skewness, kurtosis, and 30th
      95th percentile were not significantly different between the two groups. Areas
      under the receiver operator characteristics curves to differentiate patients with
      metastatic liver involvement from healthy controls without liver disease were
      0.79 for the fifth percentile and 0.95 for the SD. CONCLUSION: Whole-liver
      diffusion-weighted MRI histogram analysis showed a significant shift towards
      lower fifth percentile ADC values and higher SD in patients with colorectal liver
      metastasis compared with controls without liver disease.

PMID- 25874513
TI  - Redefining the alanine aminotransferase upper limit of normal improves the
      prediction of metabolic syndrome risk.
AB  - BACKGROUND: Multiple studies have recently proposed the lowering of upper limit
      of normal (ULN) for alanine aminotransferase (ALT) to improve the diagnostic
      sensitivity for viral hepatitides and metabolic syndrome (MS). We have tried to
      validate some of the proposed ULNs in the diagnosis of MS. METHODS: We used data
      from the HepaMeta Study conducted in 2011 in Slovakia, which explored the
      prevalence of MS in eastern Slovakia. Patients were tested for the criteria of MS
      and ALT. Different, previously published, ALT cutoffs were then used to calculate
      odds' ratios, sensitivity, specificity, and accuracy of MS and its components.
      RESULTS: Manufacturers' recommended ULN used in our institution (0.8 ukat/l, 47
      U/l for men and 0.6 ukat/l, 35 U/l for women) failed to predict any significant
      risk of MS. Lowered cutoff (72% of the original ULN) identified the patients with
      the highest age-adjusted probability of MS (odds ratio 3.194, 95% confidence
      interval 1.398-7.295). ALT was significantly associated with elevated levels of
      triacylglycerols, hyperglycemia, and obesity. CONCLUSION: In patients with MS,
      one must consider liver involvement if the patient has ALT levels in the upper
      third of the reference range. There is the need for discussion about the
      feasibility of lower ALT ULN in clinical practice.

PMID- 25874514
TI  - Determinants of long-term complications of endoscopic sphincterotomy are
      infections and high risk factors of bile duct and not sphincter of Oddi
      dysfunction.
AB  - BACKGROUND: With the popularity of endoscopic sphincterotomy (EST), long-term
      complications of EST are receiving increasingly more attention, but the
      mechanisms have not been sufficiently elucidated. AIM: This study aimed to
      investigate the relationship between long-term complications of EST and sphincter
      of Oddi (SO) function and other associated risk factors. PATIENTS AND METHODS: A
      total of 139 patients with choledocholithiasis who had undergone EST were
      consecutively enrolled, and divided into two groups: patients with long-term
      complications (LC group) and patients without complications (control group).
      Before and 2 years after EST, sphincter of Oddi manometry and bacterial culture
      were performed to evaluate the functional change in SO and infection of the
      biliary duct. RESULTS: With an average follow-up duration of 45.8 months, 25
      (18.0%) patients developed long-term complications (LC group). Compared with
      before EST, contraction amplitude and frequency of SO in both groups were
      markedly reduced after EST, but the changes were not significantly different
      between the two groups (P>0.05). The rates of bacterial infection in the biliary
      tract increased significantly in the LC group compared with the control group
      after EST: 57.1% (12/21) versus 32.7% (35/107), respectively (P=0.034), although
      these were similar before EST in both the groups. Logistic regression analysis
      showed that cholecystolithiasis, common bile duct diameter 15 mm or more, and
      maximum stone diameter 15 mm or more were major risk factors for long-term
      complications. CONCLUSION: Weakened SO function is not a decisive factor for long
      term complications of EST, which were mainly influenced by biliary tract
      infection and high risk factors of the biliary tract.

PMID- 25874515
TI  - Innovative percutaneous antegrade clearance of intrahepatic and extrahepatic
      biliary stones with the use of a hysterosalpingography catheter.
AB  - OBJECTIVES: We present a novel modified technique of percutaneous antegrade
      clearance of intrahepatic and common bile duct stones with the use of a
      hysterosalpingography balloon (HSG) catheter. METHODS: Technical tips and
      techniques used, along with the clinical results obtained in six patients whom we
      treated over a 6-month period have been described. RESULTS: The HSG balloon
      catheter is shown to demonstrate superior pushability, flexibility, and
      maneuverability in comparison with other previously described compliant balloons.
      CONCLUSIONS: The HSG balloon catheter is shown to be a really good device to
      remove intrahepatic and common bile duct stones percutaneously, allowing, where
      required, access to both the right and the left intrahepatic biliary systems from
      a single and smaller Fr hepatic bile duct access.

PMID- 25874516
TI  - Conventional clinical and pathological features fail to accurately predict
      recurrence in patients with gastric cancer staged N0.
AB  - INTRODUCTION: Despite the medical-surgical advances, even after R0 gastric
      resections, some patients without apparent metastatic disease develop cancer
      recurrence and eventually die. AIMS: We aimed to define recurrence in patients
      with node-negative gastric adenocarcinoma and to determine whether any
      clinicopathological features are predictive for recurrence. MATERIALS AND
      METHODS: This was a retrospective cohort study on patients with gastric
      adenocarcinoma, consecutively diagnosed at our institution, staged as N0M0
      between January 2000 and December 2008. RESULTS: We recruited 129 patients; 53%
      were men and 56% were older than 60 years. A total of 22% of the patients
      developed recurrence, with a mortality rate of 93%. Overall, 71% of the patients,
      N0, with recurrence presented lymphatic permeation. In univariate analysis, on
      comparing recurrent patients with those with no recurrence, age, size, T status,
      lymphatic, and venous permeation were factors that were associated significantly
      with recurrence, but in multivariate analysis, only age (odds ratio:19.5; 95%
      confidence interval: 2.3-168; P=0.008) and venous permeation (odds ratio: 6.34;
      95% confidence interval: 1.8-22.8; P=0.005) were associated with recurrence. On
      the basis of only these two factors, the proportion of missed recurrent patients
      by age and venous permeation was 13 and 39%, respectively. CONCLUSION: A total of
      22% of patients, N0, developed recurrence of their disease. Age and venous
      permeation were independent risk factors for recurrence, but on the basis of
      these factors, up to 40% of patients may be missed for recurrence. New methods to
      predict recurrence are needed.

PMID- 25874517
TI  - Clinical, biological, and endoscopic responses to adalimumab in antitumor
      necrosis factor-naive Crohn's disease: predictors of efficacy in clinical
      practice.
AB  - BACKGROUND AND AIMS: Endoscopic healing and clinical remission are important
      parameters to evaluate therapeutic efficacy in Crohn's disease. The aim of this
      study was to investigate the clinical effectiveness of adalimumab in terms of
      clinical and endoscopic response and to identify predictors of efficacy in
      clinical practice. MATERIALS AND METHODS: A prospective analysis was carried out
      of 68 antitumor necrosis factor-naive Crohn's disease patients treated with
      adalimumab for 2 years. Clinical and endoscopic response was assessed using the
      Harvey-Bradshaw index and the Simple Endoscopic Score for Crohn's disease,
      respectively. RESULTS: Adalimumab treatment was associated with clinical
      remission in 76.6, 90.6, and 87.5% of patients at 6, 12, and 24 months. Loss of
      efficacy occurred in 17.6% of cases after 24 months of therapy. Clinical
      remission with normal C-reactive protein at 2 months or with endoscopic response
      at 6 months was predictive of better outcomes. Mucosal healing rates were 17.2,
      44.7, and 39.5% and endoscopic responses were 55.1, 76.6, and 76.3% at the
      respective time points. Mucosal healing was higher in the early treatment group
      than in the group with disease of at least 5 years' duration (64.7 vs. 19.1%,
      P=0.004). Inflammatory phenotype showed a higher percentage of mucosal healing
      (70%) than stricturing (29.4%) or penetrating (27.3%) disease. CONCLUSION:
      Adalimumab was effective in providing sustained clinical remission. In patients
      in clinical remission, the C-reactive protein level at 2 months, endoscopic
      response at 6 months, or inflammatory phenotype and short disease duration could
      be considered as good predictors of efficacy.

PMID- 25874518
TI  - Azathioprine discontinuation earlier than 6 months in Crohn's disease patients
      started on anti-TNF therapy is associated with loss of response and the need for
      anti-TNF dose escalation.
AB  - OBJECTIVES: A high proportion of Crohn's disease (CD) patients lose response to
      antitumor necrosis factor (anti-TNF) and therapy needs to be intensified. We
      aimed to prospectively determine the predictors and frequency of anti-TNF loss of
      response and therefore the need for dose escalation and de-escalation in CD
      patients treated with infliximab or adalimumab. METHODS: All patients were anti
      TNF naive while concomitant azathioprine was administered for 6 months. In
      patients initially responding to anti-TNF and subsequently losing clinical
      response after the first 14 weeks of therapy, dose escalation was scheduled.
      During the follow-up period and after 1 year of intensified administration, anti
      TNF was de-escalated in patients in remission. RESULTS: A total of 161 patients
      were started on infliximab (n=96) or adalimumab (n=65); however, 29 patients
      (18.0%) did not respond to therapy and were excluded from further analysis. From
      the remaining 132 patients (infliximab=77, adalimumab=55), 31 (23.5%) needed a
      dose escalation for maintenance of remission during a median 28-month follow-up
      period. Factors associated with loss of response and therefore the need for anti
      TNF dose escalation were azathioprine discontinuation earlier than 6 months and
      smoking. Most patients achieved clinical remission (n=25, 80.6%) without other
      interventions and among these, 16 patients (64%) were successfully de-escalated
      to the standard maintenance infliximab or adalimumab dose schedule after 1 year
      of intensified anti-TNF administration. CONCLUSION: Azathioprine discontinuation
      earlier than 6 months and smoking in CD patients started on anti-TNF therapy is
      associated with loss of response and the need for anti-TNF dose escalation.

PMID- 25874519
TI  - Diverticular disease as a chronic gastrointestinal condition: experience from a
      specialist clinic.
AB  - BACKGROUND: Although diverticular disease is a prevalent condition and a
      significant burden on the healthcare system, care is devolved across
      gastrointestinal, GP, and colorectal surgery clinics. We created a specialist
      Diverticular Disease Clinic to streamline care, enhance evidence-based practice
      and provide a base for research. The aim of this study was to assess patient
      referral sources, predictors of persistent disease and surgical outcomes.
      METHODS: We retrospectively reviewed all patients attending our clinic. Patients
      younger than 50 years of age on initial presentation were considered 'younger'
      patients. Persistent symptoms lasted for at least 3 months. RESULTS: Overall, 177
      patients had confirmed diverticular disease. Patients were referred following
      hospital admission (82 patients, 46.3%) or from the community (95 patients,
      53.7%). Ninety-five patients (53.7%) had persistent symptoms. Patients with more
      than two episodes of diverticulitis were more likely to have persistent symptoms
      (P<0.0001).Following hospitalization, younger patients were 3.98 times more
      likely to develop persistent symptoms (P=0.04). This was independent of the
      severity of the original infection, as a low peak C-reactive protein level of
      less than 50 mg/L was associated with persistent symptoms (odds ratio=3.62,
      P=0.03). Over the study period, 12 patients (6.9%) had elective surgery.
      CONCLUSION: There is demand for dedicated care for patients with persistent
      symptoms from diverticular disease. Specialized clinics are a model for this
      care, provided by either gastroenterologists or surgeons, in centres with
      adequate demand. Our findings reinforce the hypotheses that chronic abdominal
      pain in diverticular disease may be related to sensation abnormalities similar to
      postinfective irritable bowel syndrome.

PMID- 25874520
TI  - Infected retroperitoneal pelvic necrosis in severe acute pancreatitis: how can we
      manage it?
AB  - OBJECTIVES: Retroperitoneal necrosis in the pelvic cavity is a rare complication
      of severe acute pancreatitis (SAP), mainly developing in critically ill patients.
      Because of its particular anatomy, it is difficult to perform drainage or
      surgery. We hypothesized that computed tomography (CT)-guided drainage is an
      effective approach for the infected retroperitoneal necrosis. The aim of this
      study is to evaluate the safety and effectiveness of CT-guided transgluteal
      drainage in SAP patients with infected retroperitoneal pelvic necrosis. MATERIALS
      AND METHODS: Twelve SAP patients with infected retroperitoneal pelvic necrosis
      underwent CT-guided transgluteal drainage with a 12-month follow-up. The safety
      and effectiveness of drainage were measured by the complication rate and the rate
      of clinical success. RESULTS: All the 12 patients underwent a successful drainage
      under the guidance of CT and their clinical symptoms disappeared within 48 h. One
      patient died of another serious complication of SAP and in the remaining 11
      patients, complete resolution was achieved without major complications. The mean
      catheter indwelling time was 21.5 days. Repeated CT during the follow-up period
      showed no recurrence in the remaining 11 patients. CONCLUSION: Transgluteal
      drainage under the guidance of CT was found to be an effective and appropriate
      approach for infected pelvic necrosis in SAP patients.

PMID- 25874521
TI  - Endoscopic ultrasonography-fine needle aspiration versus PET-CT in undiagnosed
      mediastinal and upper abdominal lymphadenopathy: a comparative clinical study.
AB  - BACKGROUND AND STUDY AIMS: The wide use of PET-CT for the staging of neoplasms
      has extended to enlarged lymph nodes of unknown origin. Nevertheless, upper
      abdominal and mediastinal nodes are accessible to endoscopic ultrasonography-fine
      needle aspiration (EUS-FNA), providing a cytological diagnosis, with a high
      diagnostic yield in previous reports. In this paper, we have compared the
      accuracy of both procedures in this particular setting. PATIENTS AND METHODS:
      After the finding of a lymphadenopathy in a conventional CT, both PET-CT and EUS
      FNA were performed. The endoscopist had no information about PET-CT results. FNA
      was performed after a systematic EUS exam, with a 25 G needle and no suction. We
      considered the pathologic results as the gold standard or, if not available, the
      patients' outcome as a surrogate marker. RESULTS: A total of 54 patients were
      included. Common locations of nodes included subcarinal space (33.3%), porta
      hepatis (31.5%), upper mediastinum (15%), peripancreatic (7.4%), and other
      locations (12.8%). Adequate specimens were obtained in 48/54 patients (89%). The
      most common diagnoses based on cytology were benign/reactive (42%), epidermoid
      carcinoma (8.4%), lymphoma (8.4%), and ductal adenocarcinoma of pancreatic origin
      (6.3%). PET was positive in 67% of patients. The sensitivity, specificity,
      positive predictive value, negative predictive value, and overall accuracy of EUS
      FNA were 91.3, 100, 100, 92.5, and 95.8%, respectively. The same values for PET
      CT were 75, 25, 50, 50, and 50%, respectively. CONCLUSION: In our series, EUS-FNA
      has proven to be the best diagnostic procedure to accurately establish the
      etiology of isolated adenopathies, showing a much better diagnostic yield than
      PET-CT, the role of which should be re-evaluated in this setting.

PMID- 25874522
TI  - Optimizing the performance of magnetic-assisted capsule endoscopy of the upper GI
      tract using multiplanar CT modelling.
AB  - BACKGROUND AND AIMS: This study used computed tomography modelling of the abdomen
      to determine the optimal placements of a magnetic capsule endoscope in the
      stomach that allows complete mucosal visualization and determined the optimal
      placement of the handheld magnet to aid pyloric traversing. MATERIALS AND
      METHODS: Using multiplanar reformatting, 100 abdominal computed tomography scans
      were analysed to assess gastric luminal visualization by a capsule endoscope from
      five fixed stations throughout the stomach. From each station, we assessed the
      ability of a capsule endoscope to visualize six gastric landmarks. The pyloric
      canal angles were calculated to create a vector. We mapped the position of this
      vector on the patient to determine the optimal placement of the magnet that would
      aid pyloric traversing. RESULTS: Complete visualization of the stomach (viewing
      all landmarks) was only achievable in up to 29% of cases when viewed from a sole
      station. Maximal visualization required combining stations. Fundal dependent
      (station 1) and opposite antral dependent (station 4) was the best, achieving
      visualization in 85% (P<0.01). The optimal positioning of the magnet to aid
      pyloric traversing was posteriorly between vertebrae T5 and L2 in an area 10 cm
      to the left and 18 cm to the right (83% cases). Age older than 55 years (P=0.03)
      and the ability to view the pylorus from station 3 (P=0.04) were associated with
      an extreme pyloric vector. CONCLUSION: Although there is some extreme variation
      in the upper gastrointestinal anatomy, the majority of cases will allow the use
      of a single standard method in performing MACE, which may be very useful for
      screening purposes.

PMID- 25874523
TI  - The diagnostic yield of preoperative staging computed tomography of the thorax in
      colorectal cancer patients without hepatic metastases.
AB  - BACKGROUND: National UK guidelines recommend preoperative computed tomography
      (CT) examination of the chest for all patients with colorectal cancer (CRC) as
      identification of thoracic metastatic disease may influence treatment plans. The
      diagnostic yield of this approach for patients without radiological evidence of
      hepatic metastases remains unclear. The aim of this study was to establish the
      impact upon treatment of chest CT examination for CRC patients without metastatic
      liver disease. PATIENTS AND METHODS: All patients diagnosed with CRC without
      liver metastases disease between December 2006 and December 2013 in a single
      institution were identified from a prospectively recorded departmental database.
      Data collected included patient demographics, disease stage and chest CT
      findings. RESULTS: There were 358 CRC patients (183 male, 175 female, median age
      70 years, range 24-96 years) without liver metastases. Colon cancer accounted for
      68% of cases with 32% of patients diagnosed with rectal cancer. The majority of
      patients (n=292, 81.6%) had no evidence of thoracic pathology during the study
      period. Lung metastases were identified in five (1.4%) patients, one of them
      subsequently diagnosed with benign pulmonary nodule. In 61 (17.0%) patients the
      lung nodules were classified as intermediate with only three subsequently
      reclassified as pulmonary metastases (n=1) or primary lung cancer (n=2).
      CONCLUSION: In the absence of liver metastases, CRC rarely spreads to the lung.
      Consequently, preoperative chest CT examination for patients without evidence of
      liver metastases may not be necessary in the majority of patients. Future studies
      are required to identify patients at high risk for pulmonary metastases who may
      benefit from this preoperative investigation.

PMID- 25874524
TI  - Massive biliary necrosis as a complication of a hereditary hemorrhagic
      telangiectasia.

PMID- 25874525
TI  - Directions of odds ratios might be inappropriate in the paper by Tafarel et al.

PMID- 25874526
TI  - Neutrophil-to-lymphocyte ratio as a predictor of fibrosis in inactive hepatitis B
      carriers.

PMID- 25874527
TI  - On status of serum iron parameters in chronic hepatitis and cirrhosis: comments
      on the article by Mao et al.

PMID- 25874528
TI  - Diabetes is associated with an increased risk of in-hospital mortality in liver
      cirrhosis with acute upper gastrointestinal bleeding.

PMID- 25874531
TI  - Inkjet printing of silver nanowire networks.
AB  - The development of printed electronics will require the ability to deposit a wide
      range of nanomaterials using printing techniques. Here we demonstrate the
      controlled deposition of networks of silver nanowires in well-defined patterns by
      inkjet printing from an optimized isopropyl alcohol-diethylene glycol dispersion.
      We find that great care must be taken while producing the ink and during solvent
      evaporation. The resultant networks have good electrical properties, displaying
      sheet resistances as low as 8 Omega/? and conductivities as high as 10(5) S/m.
      Such optimized performances were achieved for line widths of 1-10 mm and network
      thicknesses of 0.5-2 MUm deposited from ~10-20 passes while using processing
      temperatures of no more than 110  degrees C. Thin networks are semitransparent
      with dc to optical conductivity ratios of ~40. 

PMID- 25874530
TI  - The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is associated
      with increased body mass index and insulin resistance measures in bipolar
      disorder and schizophrenia.
AB  - OBJECTIVES: We tested the hypothesis that a common functional variant in brain
      derived neurotrophic factor (BDNF), Val66Met, which has been shown to be
      associated with increased body mass index (BMI) in schizophrenia (SCZ) and
      schizoaffective disorder (SAD), is also associated with antipsychotic-induced
      weight gain in bipolar disorder (BPD). Association of Val66Met with other
      metabolic measures, including high- and low-density cholesterol, triglycerides,
      total cholesterol, fasting blood glucose, and hemoglobin A1c, was also tested.
      METHODS: This was a 12-month, prospective, randomized trial of two atypical
      antipsychotic drugs (APDs) with moderate (risperidone) or high (olanzapine) risk
      to cause weight gain. Subjects were diagnosed as having BPD (n = 90) and SCZ or
      SAD (n = 76). RESULTS: BMI was significantly greater in all diagnoses for Met66
      allele carriers at six months (p = 0.01). Met66 carriers with BPD showed a
      greater increase in the triglycerides/high-density (HDL) cholesterol ratio (p =
      0.01), a key marker for metabolic syndrome related to insulin resistance, and log
      triglycerides (p = 0.04), after three or six months of treatment. Met66 carriers
      had the greatest increase in log-triglycerides (p = 0.03) and triglycerides/HDL
      cholesterol ratio after three months of treatment with risperidone (p = 0.003),
      and the highest BMI at six months (p = 0.01). CONCLUSIONS: The positive
      association of BNDF Val66Met with high BMI values replicates previous findings in
      patients with SCZ and indicates the BDNF Val66Met genotype as a potential risk
      factor for obesity and insulin resistance measures in patients with BPD receiving
      antipsychotics as well.

PMID- 25874532
TI  - Size control of in vitro synthesized magnetite crystals by the MamC protein of
      Magnetococcus marinus strain MC-1.
AB  - Magnetotactic bacteria are a diverse group of prokaryotes that share the unique
      ability of biomineralizing magnetosomes, which are intracellular, membrane
      bounded crystals of either magnetite (Fe3O4) or greigite (Fe3S4). Magnetosome
      biomineralization is mediated by a number of specific proteins, many of which are
      localized in the magnetosome membrane, and thus is under strict genetic control.
      Several studies have partially elucidated the effects of a number of these
      magnetosome-associated proteins in the control of the size of magnetosome
      magnetite crystals. However, the effect of MamC, one of the most abundant
      proteins in the magnetosome membrane, remains unclear. In this present study,
      magnetite nanoparticles were synthesized inorganically in free-drift experiments
      at 25  degrees C in the presence of different concentrations of the iron-binding
      recombinant proteins MamC and MamCnts (MamC without its first transmembrane
      segment) from the marine, magnetotactic bacterium Magnetococcus marinus strain MC
      1 and three commercial proteins [alpha-lactalbumin (alpha-Lac), myoglobin (Myo),
      and lysozyme (Lyz)]. While no effect was observed on the size of magnetite
      crystals formed in the presence of the commercial proteins, biomimetic synthesis
      in the presence of MamC and MamCnts at concentrations of 10-60 MUg/mL resulted in
      the production of larger and more well-developed magnetite crystals (~30-40 nm)
      compared to those of the control (~20-30 nm; magnetite crystals grown protein
      free). Our results demonstrate that MamC plays an important role in the control
      of the size of magnetite crystals and could be utilized in biomimetic synthesis
      of magnetite nanocrystals.

PMID- 25874533
TI  - Antibacterial products of marine organisms.
AB  - Marine organisms comprising microbes, plants, invertebrates, and vertebrates
      elaborate an impressive array of structurally diverse antimicrobial products
      ranging from small cyclic compounds to macromolecules such as proteins. Some of
      these biomolecules originate directly from marine animals while others arise from
      microbes associated with the animals. It is noteworthy that some of the
      biomolecules referred to above are structurally unique while others belong to
      known classes of compounds, peptides, and proteins. Some of the antibacterial
      agents are more active against Gram-positive bacteria while others have higher
      effectiveness on Gram-negative bacteria. Some are efficacious against both Gram
      positive and Gram-negative bacteria and against drug-resistant strains as well.
      The mechanism of antibacterial action of a large number of the chemically
      identified antibacterial agents, possible synergism with currently used
      antibiotics, and the issue of possible toxicity on mammalian cells and tissues
      await elucidation. The structural characteristics pivotal to antibacterial
      activity have been ascertained in only a few studies. Demonstration of efficacy
      of the antibacterial agents in animal models of bacterial infection is highly
      desirable. Structural characterization of the active principles present in
      aqueous and organic extracts of marine organisms with reportedly antibacterial
      activity would be desirable. 

PMID- 25874534
TI  - Salt Stability - The Effect of pHmax on Salt to Free Base Conversion.
AB  - PURPOSE: The aim of this study was to investigate how the disproportionation
      process can be impacted by the properties of the salt, specifically pHmax.
      METHODS: Five miconazole salts and four sertraline salts were selected for this
      study. The extent of conversion was quantified using Raman spectroscopy. A
      mathematical model was utilized to estimate the theoretical amount of conversion.
      RESULTS: A trend was observed that for a given series of salts of a particular
      basic compound (both sertraline and miconazole are bases), the extent of
      disproportionation increases as pHmax decreases. Miconazole phosphate monohydrate
      and sertraline mesylate, although exhibiting significantly different pHmax values
      (more than 2 units apart), underwent a similar extent of disproportionation,
      which may be attributed to the lower buffering capacity of sertraline salts.
      CONCLUSION: This work shows that the disproportionation tendency can be
      influenced by pHmax and buffering capacity and thus highlights the importance of
      selecting the appropriate salt form during the screening process in order to
      avoid salt-to-free form conversion.

PMID- 25874536
TI  - What's new in Shock? May 2015.

PMID- 25874535
TI  - PRMT1 promotes glucose toxicity-induced beta cell dysfunction by regulating the
      nucleo-cytoplasmic trafficking of PDX-1 in a FOXO1-dependent manner in INS-1
      cells.
AB  - Protein N-arginine methyltransferase-1 (PRMT1), the major asymmetric arginine
      methyltransferase, plays important roles in various cellular processes. Previous
      reports have demonstrated that levels and activities of PRMT1 can vary in animals
      with type 2 diabetes mellitus. The aim of this study was to assess the expression
      and mechanism of action of PRMT1 during glucose toxicity-induced beta cell
      dysfunction. Liposome-mediated gene transfection was used to transfect INS-1
      cells with siPRMT1, which inhibits PRMT1 expression, and pALTER-FOXO1, which
      overexpresses forkhead box protein O1 (FOXO1). The cells were then cultured in
      media containing 5.6 or 25 mmol/L glucose with or without the small molecule
      PRMT1 inhibitor AMI-1 for 48 h. The protein levels of PRMT1, the arginine
      methylated protein alpha-metR, FOXO1, Phospho-FOXO1, pancreas duodenum homeobox-1
      (PDX-1), and the intracellular localization of PDX-1 and FOXO1 were then measured
      by western blotting. FOXO1 methylation was detected by immunoprecipitated with
      anti-PRMT1 antibody and were immunoblotted with alpha-metR. The levels of insulin
      mRNA were measured by real-time fluorescence quantitative PCR. Glucose-stimulated
      insulin secretion (GSIS) and intracellular insulin content were measured using
      radioimmunoassays. Intracellular Ca(2+) ([Ca(2+)]i) was detected using Fura-2 AM.
      Intracellular cAMP levels were measured using ELISA. Chronic exposure to high
      glucose impaired insulin secretion, decreased insulin mRNA levels and insulin
      content, increased intracellular [Ca(2+)]i and cAMP levels, and abolishes their
      responses to glucose. Inhibiting PRMT1 expression improved insulin secretion,
      increased mRNA levels and insulin content by regulating the intracellular
      translocation of PDX-1 and FOXO1, decreasing the methylation of FOXO1, and
      reducing intracellular [Ca(2+)]i and cAMP concentrations. Transient
      overexpression of constitutively active FOXO1 in nuclear reversed the AMI-1
      induced improvement of beta cell function without changing arginine methylation.
      It is concluded therefore that PRMT1 regulates GSIS in INS-1 cells, through
      enhanced methylation-induced nuclear localization of FOXO1, which subsequently
      suppresses the nuclear localization of PDX-1. Our results suggest a novel
      mechanism that might contribute to the deficient insulin secretion observed under
      conditions of chronically hyperglycemia.

PMID- 25874537
TI  - Lipopolysaccharide-binding protein (LBP) blockade augments the protective effect
      of granulocyte colony-stimulating factor (G-CSF) in a rat sepsis model.
AB  - The effect of granulocyte colony-stimulating factor (G-CSF) on sepsis is
      discussed controversially in clinical studies. We previously demonstrated that G
      CSF treatment induced lipopolysaccharide (LPS) sensitization via up-regulation of
      LPS-binding protein (LBP). We hypothesized that the futile effect of G-CSF
      treatment in sepsis might be due to its ability to up-regulate LBP. Therefore,
      blockade of LBP may attenuate the G-CSF-induced LPS sensitization and protect
      animals from polymicrobial sepsis. Endogenous LBP levels were up-regulated by
      pretreatment with G-CSF, and the LBP protein was blocked by administration of a
      specific blocking peptide-LBPK95A. Polymicrobial sepsis was induced by
      intraperitoneal injection of feces slurry. Rats were monitored every 3 up to 72 h
      to observe the survival rate. Tissue injury, bacterial infiltration, local
      inflammatory response, and neutrophil infiltration at 0, 2, and 12 h after the
      septic insult were analyzed. The survival benefit of G-CSF pretreatment was
      improved when combined with LBPK95A treatment (control vs. G-CSF vs. combi: 36%
      vs. 56% vs. 93%; P < 0.05). Combined treatment of G-CSF and LBPK95A was
      associated with the minimal tissue damage. Treatment with LBPK95A significantly
      inhibited the neutrophil infiltration without interfering with the bacterial
      clearance. The G-CSF-induced inflammatory sensitization effect was inhibited by
      LBPK95A, indicated by the decrease of cytokines expression, and the activation of
      nuclear factor kappa B and signal transducer and activator of transcription 3
      signaling pathway. In conclusion, these results suggested that the effect of
      prophylactic augmentation of the host's response via G-CSF pretreatment was
      further enhanced by inhibition of the up-regulation of LBP. 

PMID- 25874539
TI  - Effect of topical insulin application on wound neutrophil function.
AB  - This study observed the quantity and functions of wound neu- trophils after
      topical insulin treatment and investigated the effect of insulin on the wound
      inflammatory response, as well as the mechanism of insulin-induced wound healing.
      METHODS: Full-thickness excisional wounds were made on the dorsal symmetrical
      site of C57BL/6J mice. The wounds were treated with either 0.03U insulin/20 MUL
      saline or 20 MUL saline. The healing times and healing rates of the wounds were
      recorded. The wounds and adjacent tissues were collected during the first 3
      consecutive days after the injury. Quantification of myeloid dif- ferentiation
      antigen Gr-1, myeloperoxidase (MPO), malondialdehyde (MDA), and macrophage
      inflammatory protein-2 (MIP-2) were mea- sured by Western blotting, biochemical
      analysis, and real-time poly- merase chain reaction (PCR), respectively. RESULTS:
      The healing time of insulin-treated wounds was significantly decreased compared
      with the saline-treated wounds. The wound closure rates at days 5 and 7 after
      injury were significantly higher with insulin treatment than with saline
      treatment. Additionally, wound neutrophil infiltration was suppressed by insulin
      treatment within the first 2 days after injury. Real-time PCR revealed insulin
      treatment significantly inhibited MIP-2 expression within 2 days after injury (P
      P <0.05), whereas MIP-2 expression in both groups decreased to a similar level at
      3 days after injury. There was no statistical difference in MPO or MDA content
      between the insulin treatment and control group. CONCLUSION: Topical insulin
      application decreased neutrophil infiltration by inhibiting MIP-2 expression and
      advanced neutrophil resolution. It has been reported that insulin pro- motes
      neutrophil functions; therefore, the present results, along with previous
      findings, suggest there is a delicate regulation of insulin on wound inflammatory
      response during the healing process.

PMID- 25874540
TI  - Tissue augmentation and replacement of a heel fat pad with a decellularized
      sterile human dermal matrix.
AB  - The use of xenografts and allografts has been primarily direct- ed at chronic
      wounds and tendon repair. Currently, there are no known devices in this category
      that can successfully be used to augment tis- sue. Patients who have undergone
      trauma and subsequent surgery, par- ticularly in weight-bearing areas, may
      experience pain with pressure or ambulation at the site. This report illustrates
      the use of an allograft for tissue augmentation in a young individual who was
      involved in a motor vehicle accident resulting in loss of the plantar fat pad. An
      allograft was successfully used for tissue replacement, thereby reducing pain and
      facilitating weight-bearing ambulation.    . 

PMID- 25874538
TI  - The vitamin D, ionised calcium and parathyroid hormone axis of cerebral capillary
      function: therapeutic considerations for vascular-based neurodegenerative
      disorders.
AB  - Blood-brain barrier dysfunction characterised by brain parenchymal extravasation
      of plasma proteins may contribute to risk of neurodegenerative disorders, however
      the mechanisms for increased capillary permeability are not understood.
      Increasing evidence suggests vitamin D confers central nervous system benefits
      and there is increasing demand for vitamin D supplementation. Vitamin D may
      influence the CNS via modulation of capillary function, however such effects may
      be indirect as it has a central role in maintaining calcium homeostasis, in
      concert with calcium regulatory hormones. This study utilised an integrated
      approach and investigated the effects of vitamin D supplementation, parathyroid
      tissue ablation (PTX), or exogenous infusion of parathyroid hormone (PTH) on
      cerebral capillary integrity. Parenchymal extravasation of immunoglobulin G (IgG)
      was used as a marker of cerebral capillary permeability. In C57BL/6J mice and
      Sprague Dawley rats, dietary vitamin D was associated with exaggerated abundance
      of IgG within cerebral cortex (CTX) and hippocampal formation (HPF). Vitamin D
      was also associated with increased plasma ionised calcium (iCa) and decreased
      PTH. A response to dose was suggested and parenchymal effects persisted for up to
      24 weeks. Ablation of parathyroid glands increased CTX- and HPF-IgG abundance
      concomitant with a reduction in plasma iCa. With the provision of PTH, iCa levels
      increased, however the PTH treated animals did not show increased cerebral
      permeability. Vitamin D supplemented groups and rats with PTH-tissue ablation
      showed modestly increased parenchymal abundance of glial-fibrillary acidic
      protein (GFAP), a marker of astroglial activation. PTH infusion attenuated GFAP
      abundance. The findings suggest that vitamin D can compromise capillary integrity
      via a mechanism that is independent of calcium homeostasis. The effects of
      exogenous vitamin D supplementation on capillary function and in the context of
      prevention of vascular neurodegenerative conditions should be considered in the
      context of synergistic effects with calcium modulating hormones. 

PMID- 25874541
TI  - The effect of pentoxifylline on chronic venous ulcers.
AB  - Venous ulcers affect approximately 1% of the world's popula- tion, increasing
      health care expenditures and decreasing quality of life. Several hypotheses may
      help explain their origin. Insufficient veins or valves or impaired muscle
      function may lead to abnormal calf muscle pump function that can elevate
      ambulatory venous pressure. The aim of this study was to evaluate the efficacy of
      pentoxifylline in treating chronic venous ulcers. METHODS: From May 2009 to March
      2010, 40 patients with chronic venous ulcers were randomly assigned to 2 groups:
      a standard treatment group that received compression therapy or an in- tervention
      group that received oral pentoxifylline (400 mg, 3 times daily) in addition to
      compression therapy. Time duration of wound healing, edema, pain, and ulcer size
      in the 2 groups were studied. For all tests, P P <0.05 was considered
      significant. RESULTS: The median duration of com- plete wound healing was 4
      months in the intervention group and 6.25 months in the standard treatment group
      (P = 0.007). Recovery from pain and edema was not statistically significant after
      3 months' follow-up in either group. After 3 months of treatment, ulcer size
      decreased more in the intervention group compared to the standard treatment group
      (P = 0.02). Pentoxifylline in association with compression therapy decreases both
      time to complete wound healing and ulcer size.  .

PMID- 25874542
TI  - Simvastatin improves incisional wound healing in a rat model: an experimental
      study.
AB  - This study investigated the effect of simvastatin on the heal- ing process of
      abdominal wall wounds in rats. METHODS: The study was performed with adult female
      Wistar-Albino rats. Control group (n = 20) rats were fed standard laboratory diet
      until 12 hours before sur- gery. Study group (n = 20) rats received oral
      simvastatin therapy with an orogastric tube (10 mg/kg once a day) for 7 days
      until 12 hours before surgery. Each rat was anesthetized, and a 4 cm-long midline
      laparotomy was performed. Ten animals from each group were killed at
      postoperative days (PODs) 7 and 14. Breaking strength analysis was measured, and
      the abdominal incision wounds were examined histolog- ically. RESULTS:
      Hydroxyproline levels and tensile strength of abdominal fascia were significantly
      higher in the study group on PODs 7 and 14 compared to the control group. The
      granulation tissue fibroblast matu- ration scores on POD 7, and both collagen
      deposition scores and neo- vascularization scores on PODs 7 and 14, were found to
      be statistically significantly higher in the simvastatin treatment group compared
      to the control group, based on the results of the histologic tissue examina-
      tions. CONCLUSION: Simvastatin can be used as a supporting therapy in wound
      healing.    .

PMID- 25874543
TI  - Erratum to: Controlled Motion with the XL-TDR Lateral-Approach Lumbar Total Disk
      Replacement: In Vitro Kinematic Investigation (J Neurol Surg A Cent Eur Neurosurg
      2015;76(2):133-138).

PMID- 25874545
TI  - Has introduction of rapid drug susceptibility testing at diagnosis impacted
      treatment outcomes among previously treated tuberculosis patients in Gujarat,
      India?
AB  - BACKGROUND: Revised National TB Control Programme (RNTCP) in India recommends
      that all previously-treated TB (PT) patients are offered drug susceptibility
      testing (DST) at diagnosis, using rapid diagnostics and screened out for
      rifampicin resistance before being treated with standardized, eight-month,
      retreatment regimen. This is intended to improve the early diagnosis of
      rifampicin resistance and its appropriate management and improve the treatment
      outcomes among the rest of the patients. In this state-wide study from Gujarat,
      India, we assess proportion of PT patients underwent rapid DST at diagnosis and
      the impact of this intervention on their treatment outcomes. METHODS: This is a
      retrospective cohort study involving review of electronic patient-records
      maintained routinely under RNTCP. All PT patients registered for treatment in
      Gujarat during January-June 2013 were included. Information on DST and treatment
      outcomes were extracted from 'presumptive DR-TB patient register' and TB
      treatment register respectively. We performed a multivariate analysis to assess
      if getting tested is independently associated with unfavourable outcomes (death,
      loss-to-follow-up, failure, transfer out). RESULTS: Of 5,829 PT patients,
      5306(91%) were tested for drug susceptibility with rapid diagnostics. Overall,
      71% (4,113) TB patients were successfully treated - 72% among tested versus 60%
      among non-tested. Patients who did not get tested at diagnosis had a 34% higher
      risk of unsuccessful outcomes as compared to those who got tested (aRR - 1.34;
      95% CI 1.20-1.50) after adjusting for age, sex, HIV status and type of TB.
      Unfavourable outcomes (particularly failure and switched to category IV) were
      higher among INH-resistant patients (39%) as compared to INH-sensitive (29%).
      CONCLUSION: Offering DST at diagnosis improved the treatment outcomes among PT
      patients. However, even among tested, treatment outcomes remained suboptimal and
      were related to INH resistance and high loss-to-follow-up. These need to be
      addressed urgently for further progress.

PMID- 25874544
TI  - Determinants of vaccine immunogenicity in HIV-infected pregnant women: analysis
      of B and T cell responses to pandemic H1N1 monovalent vaccine.
AB  - Influenza infections have high frequency and morbidity in HIV-infected pregnant
      women, underscoring the importance of vaccine-conferred protection. To identify
      the factors that determine vaccine immunogenicity in this group, we characterized
      the relationship of B- and T-cell responses to pandemic H1N1 (pH1N1) vaccine with
      HIV-associated immunologic and virologic characteristics. pH1N1 and seasonal-H1N1
      (sH1N1) antibodies were measured in 119 HIV-infected pregnant women after two
      double-strength pH1N1 vaccine doses. pH1N1-IgG and IgA B-cell FluoroSpot, pH1N1-
      and sH1N1-interferon gamma (IFNgamma) and granzyme B (GrB) T-cell FluoroSpot, and
      flow cytometric characterization of B- and T-cell subsets were performed in 57
      subjects. pH1N1-antibodies increased after vaccination, but less than previously
      described in healthy adults. pH1N1-IgG memory B cells (Bmem) increased, IFNgamma
      effector T-cells (Teff) decreased, and IgA Bmem and GrB Teff did not change.
      pH1N1-antibodies and Teff were significantly correlated with each other and with
      sH1N1-HAI and Teff, respectively, before and after vaccination. pH1N1-antibody
      responses to the vaccine significantly increased with high proportions of CD4+,
      low CD8+ and low CD8+HLADR+CD38+ activated (Tact) cells. pH1N1-IgG Bmem responses
      increased with high proportions of CD19+CD27+CD21- activated B cells (Bact), high
      CD8+CD39+ regulatory T cells (Treg), and low CD19+CD27-CD21- exhausted B cells
      (Bexhaust). IFNgamma-Teff responses increased with low HIV plasma RNA,
      CD8+HLADR+CD38+ Tact, CD4+FoxP3+ Treg and CD19+IL10+ Breg. In conclusion, pre
      existing antibody and Teff responses to sH1N1 were associated with increased
      responses to pH1N1 vaccination in HIV-infected pregnant women suggesting an
      important role for heterosubtypic immunologic memory. High CD4+% T cells were
      associated with increased, whereas high HIV replication, Tact and Bexhaust were
      associated with decreased vaccine immunogenicity. High Treg increased antibody
      responses but decreased Teff responses to the vaccine. The proportions of
      immature and transitional B cells did not affect the responses to vaccine.
      Increased Bact were associated with high Bmem responses to the vaccine. 

PMID- 25874546
TI  - Improved outcome with early rifampicin combination treatment in methicillin
      sensitive Staphylococcus aureus bacteraemia with a deep infection focus - a
      retrospective cohort study.
AB  - INTRODUCTION: Rifampicin has been used as adjunctive therapy in Staphylococcus
      aureus bacteraemia (SAB) with a deep infection focus. However, data for
      prognostic impact of rifampicin therapy is unestablished including the optimal
      initiation time point. We studied the impact of rifampicin therapy and the
      optimal initiation time for rifampicin treatment on prognosis in methicillin
      sensitive S. aureus bacteraemia with a deep infection. METHODS: Retrospective,
      multicentre study in Finland including 357 SAB patients with a deep infection
      focus. Patients with alcoholism, liver disease or patients who died within 3 days
      were excluded. Patients were categorised according to duration of rifampicin
      therapy and according to whether rifampicin was initiated early (within 7 days)
      or late (7 days after) after the positive blood cultures. Primary end point was
      90 days mortality. RESULTS: Twenty-seven percent of patients received no
      rifampicin therapy, 14% received rifampicin for 1-13 days whereas 59% received
      rifampicin >=14 days. The 90 day mortality was; 26% for patients treated without
      rifampicin, 16% for rifampicin therapy of any length and 10% for early onset
      rifampicin therapy >=14 days. Lack of rifampicin therapy increased (OR 1.89,
      p=0.026), rifampicin of any duration decreased (OR 0.53, p=0.026) and rifampicin
      therapy >=14 days with early onset lowered the risk for a fatal outcome (OR 0.33,
      p<0.01) during 90 days follow-up. CONCLUSION: Rifampicin adjunctive therapy for
      at least 14 days and initiated within 7 days of positive blood culture associated
      with improved outcome among SAB patients with a deep infection.

PMID- 25874547
TI  - Development and evolution of dentition pattern and tooth order in the skates and
      rays (batoidea; chondrichthyes).
AB  - Shark and ray (elasmobranch) dentitions are well known for their multiple
      generations of teeth, with isolated teeth being common in the fossil record.
      However, how the diverse dentitions characteristic of elasmobranchs form is still
      poorly understood. Data on the development and maintenance of the dental
      patterning in this major vertebrate group will allow comparisons to other
      morphologically diverse taxa, including the bony fishes, in order to identify
      shared pattern characters for the vertebrate dentition as a whole. Data is
      especially lacking from the Batoidea (skates and rays), hence our objective is to
      compile data on embryonic and adult batoid tooth development contributing to
      ordering of the dentition, from cleared and stained specimens and micro-CT scans,
      with 3D rendered models. We selected species (adult and embryonic) spanning
      phylogenetically significant batoid clades, such that our observations may raise
      questions about relationships within the batoids, particularly with respect to
      current molecular-based analyses. We include developmental data from embryos of
      recent model organisms Leucoraja erinacea and Raja clavata to evaluate the
      earliest establishment of the dentition. Characters of the batoid dentition
      investigated include alternate addition of teeth as offset successional tooth
      rows (versus single separate files), presence of a symphyseal initiator region
      (symphyseal tooth present, or absent, but with two parasymphyseal teeth) and a
      restriction to tooth addition along each jaw reducing the number of tooth
      families, relative to addition of successor teeth within each family. Our
      ultimate aim is to understand the shared characters of the batoids, and whether
      or not these dental characters are shared more broadly within elasmobranchs, by
      comparing these to dentitions in shark outgroups. These developmental
      morphological analyses will provide a solid basis to better understand dental
      evolution in these important vertebrate groups as well as the general
      plesiomorphic vertebrate dental condition. 

PMID- 25874549
TI  - Correction: proteomic analysis of mitochondrial-associated ER membranes (MAM)
      during RNA virus infection reveals dynamic changes in protein and organelle
      trafficking.

PMID- 25874548
TI  - Common variants of KCNJ10 are associated with susceptibility and anti-epileptic
      drug resistance in Chinese genetic generalized epilepsies.
AB  - To explore genetic mechanism of genetic generalized epilepsies (GGEs) is
      challenging because of their complex heritance pattern and genetic heterogeneity.
      KCNJ10 gene encodes Kir4.1 channels and plays a major role in modulating resting
      membrane potentials in excitable cells. It may cause GGEs if mutated. The purpose
      of this study was to investigate the possible association between KCNJ10 common
      variants and the susceptibility and drug resistance of GGEs in Chinese
      population. The allele-specific MALDI-TOF mass spectrometry method was used to
      assess 8 single nucleotide polymorphisms (SNPs) of KCNJ10 in 284 healthy controls
      and 483 Chinese GGEs patients including 279 anti-epileptic drug responsive
      patients and 204 drug resistant patients. We found the rs6690889 TC+TT genotypes
      were lower frequency in the GGEs group than that in the healthy controls (6.7% vs
      9.5%, p = 0.01, OR = 0.50[0.29-0.86]). The frequency of rs1053074 G allele was
      lower in the childhood absence epilepsy (CAE) group than that in the healthy
      controls (28.4% vs 36.2%, p = 0.01, OR = 0.70[0.53-0.93]). The frequency of
      rs12729701 G allele and AG+GG genotypes was lower in the CAE group than that in
      the healthy controls (21.2% vs 28.4%, p = 0.01, OR = 0.74[0.59-0.94] and 36.3% vs
      48.1%, p = 0.01, OR = 0.83[0.72-0.96], respectively). The frequency of rs12402969
      C allele and the CC+CT genotypes were higher in the GGEs drug responsive patients
      than that in the drug resistant patients (9.3% vs 5.6%, OR = 1.73[1.06-2.85], p =
      0.026 and 36.3% vs 48.1%, p = 0.01, OR = 0.83[0.72-0.96], respectively). This
      study identifies potential SNPs of KCNJ10 gene that may contribute to seizure
      susceptibility and anti-epileptic drug resistance. 

PMID- 25874550
TI  - Factors associated with seasonal influenza vaccination in pregnant women.
AB  - BACKGROUND: This observational study followed a cohort of pregnant women during
      the 2010-2011 influenza season to determine factors associated with vaccination.
      METHODS: Participants were 1105 pregnant women who completed a survey assessing
      health beliefs related to vaccination upon enrollment and were then followed to
      determine vaccination status by the end of the 2010-2011 influenza season. We
      conducted univariate and multivariate analyses to explore factors associated with
      vaccination status and a factor analysis of survey items to identify health
      beliefs associated with vaccination. RESULTS: Sixty-three percent (n=701) of the
      participants were vaccinated. In the univariate analyses, multiple factors were
      associated with vaccination status, including maternal age, race, marital status,
      educational level, and gravidity. Factor analysis identified two health belief
      factors associated with vaccination: participant's positive views (factor 1) and
      negative views (factor 2) of influenza vaccination. In a multivariate logistic
      regression model, factor 1 was associated with increased likelihood of
      vaccination (adjusted odds ratio [aOR]=2.18; 95% confidence interval [CI]=1.72
      2.78), whereas factor 2 was associated with decreased likelihood of vaccination
      (aOR=0.36; 95% CI=0.28-0.46). After controlling for the two health belief factors
      in multivariate analyses, demographic factors significant in univariate analyses
      were no longer significant. Women who received a provider recommendation were
      about three times more likely to be vaccinated (aOR=3.14; 95% CI=1.99-4.96).
      CONCLUSION: Pregnant women's health beliefs about vaccination appear to be more
      important than demographic and maternal factors previously associated with
      vaccination status. Provider recommendation remains one of the most critical
      factors influencing vaccination during pregnancy.

PMID- 25874551
TI  - Caste-specific differences in hindgut microbial communities of honey bees (Apis
      mellifera).
AB  - Host-symbiont dynamics are known to influence host phenotype, but their role in
      social behavior has yet to be investigated. Variation in life history across
      honey bee (Apis mellifera) castes may influence community composition of gut
      symbionts, which may in turn influence caste phenotypes. We investigated the
      relationship between host-symbiont dynamics and social behavior by characterizing
      the hindgut microbiome among distinct honey bee castes: queens, males and two
      types of workers, nurses and foragers. Despite a shared hive environment and
      mouth-to-mouth food transfer among nestmates, we detected separation among gut
      microbiomes of queens, workers, and males. Gut microbiomes of nurses and foragers
      were similar to previously characterized honey bee worker microbiomes and to each
      other, despite differences in diet, activity, and exposure to the external
      environment. Queen microbiomes were enriched for bacteria that may enhance
      metabolic conversion of energy from food to egg production. We propose that the
      two types of workers, which have the highest diversity of operational taxonomic
      units (OTUs) of bacteria, are central to the maintenance of the colony
      microbiome. Foragers may introduce new strains of bacteria to the colony from the
      environment and transfer them to nurses, who filter and distribute them to the
      rest of the colony. Our results support the idea that host-symbiont dynamics
      influence microbiome composition and, reciprocally, host social behavior. 

PMID- 25874552
TI  - Hydrological modelling for siberian crane Grus Leucogeranus stopover sites in
      northeast China.
AB  - Habitat loss is one of the key factors underlying the decline of many waterbird
      species, including Siberian Crane (Grus leucogeranus), a threatened species
      worldwide. Wetlands are the primary stopover for many waterbirds and restoration
      of these wetlands involves both hydrological restoration and water resource
      management. To protect the stopover sites of Siberian Cranes, we collected
      Siberian Crane stopover numbers, meteorological and hydrological data, and remote
      sensing data from 2008 to 2011 in Momoge National Nature Reserve, one of the
      largest wetlands in northeastern China. A model was developed to estimate the
      suitability of Siberian Crane stopover sites. According to our results, the most
      suitable daily water level for Siberian Cranes between 2008 and 2012 occurred in
      the spring of 2008 and in the Scirpus planiculmis growing season and autumn of
      2010. We suggest a season-dependent water management strategy in order to provide
      suitable conditions at Siberian Crane stopover sites. 

PMID- 25874554
TI  - Correction: trans-kingdom horizontal DNA transfer from bacteria to yeast is
      highly plastic due to natural polymorphisms in auxiliary nonessential recipient
      genes.

PMID- 25874553
TI  - On putative periodontal pathogens: an epidemiological perspective.
AB  - The current understanding on the role of microbiology on periodontitis causation
      is reviewed. An appraisal of the literature reveals several issues that have
      limited the attempts to investigate candidate periodontal pathogens as causes of
      periodontitis and confirms that only limited epidemiological evidence is
      available. Several aspects of the contemporary understanding on causal inference
      are discussed with examples for periodontitis. 

PMID- 25874555
TI  - Cell type-specific separation of subicular principal neurons during network
      activities.
AB  - The hippocampal output structure, the subiculum, expresses two major memory
      relevant network rhythms, sharp wave ripple and gamma frequency oscillations. To
      this date, it remains unclear how the two distinct types of subicular principal
      cells, intrinsically bursting and regular spiking neurons, participate in these
      two network rhythms. Using concomitant local field potential and intracellular
      recordings in an in vitro mouse model that allows the investigation of both
      network rhythms, we found a cell type-specific segregation of principal neurons
      into participating intrinsically bursting and non-participating regular spiking
      cells. However, if regular spiking cells were kept at a more depolarized level,
      they did participate in a specific manner, suggesting a potential bimodal working
      model dependent on the level of excitation. Furthermore, intrinsically bursting
      and regular spiking cells exhibited divergent intrinsic membrane and synaptic
      properties in the active network. Thus, our results suggest a cell-type-specific
      segregation of principal cells into two separate groups during network
      activities, supporting the idea of two parallel streams of information processing
      within the subiculum. 

PMID- 25874556
TI  - A general framework for thermodynamically consistent parameterization and
      efficient sampling of enzymatic reactions.
AB  - Kinetic models provide the means to understand and predict the dynamic behaviour
      of enzymes upon different perturbations. Despite their obvious advantages,
      classical parameterizations require large amounts of data to fit their
      parameters. Particularly, enzymes displaying complex reaction and regulatory
      (allosteric) mechanisms require a great number of parameters and are therefore
      often represented by approximate formulae, thereby facilitating the fitting but
      ignoring many real kinetic behaviours. Here, we show that full exploration of the
      plausible kinetic space for any enzyme can be achieved using sampling strategies
      provided a thermodynamically feasible parameterization is used. To this end, we
      developed a General Reaction Assembly and Sampling Platform (GRASP) capable of
      consistently parameterizing and sampling accurate kinetic models using minimal
      reference data. The former integrates the generalized MWC model and the
      elementary reaction formalism. By formulating the appropriate thermodynamic
      constraints, our framework enables parameterization of any oligomeric enzyme
      kinetics without sacrificing complexity or using simplifying assumptions. This
      thermodynamically safe parameterization relies on the definition of a reference
      state upon which feasible parameter sets can be efficiently sampled. Uniform
      sampling of the kinetics space enabled dissecting enzyme catalysis and revealing
      the impact of thermodynamics on reaction kinetics. Our analysis distinguished
      three reaction elasticity regions for common biochemical reactions: a steep
      linear region (0> DeltaGr >-2 kJ/mol), a transition region (-2> DeltaGr >-20
      kJ/mol) and a constant elasticity region (DeltaGr <-20 kJ/mol). We also applied
      this framework to model more complex kinetic behaviours such as the monomeric
      cooperativity of the mammalian glucokinase and the ultrasensitive response of the
      phosphoenolpyruvate carboxylase of Escherichia coli. In both cases, our approach
      described appropriately not only the kinetic behaviour of these enzymes, but it
      also provided insights about the particular features underpinning the observed
      kinetics. Overall, this framework will enable systematic parameterization and
      sampling of enzymatic reactions. 

PMID- 25874557
TI  - Characterization of microsporidia-induced developmental arrest and a
      transmembrane leucine-rich repeat protein in Caenorhabditis elegans.
AB  - Microsporidia comprise a highly diverged phylum of intracellular, eukaryotic
      pathogens, with some species able to cause life-threatening illnesses in
      immunocompromised patients. To better understand microsporidian infection in
      animals, we study infection of the genetic model organism Caenorhabditis elegans
      and a species of microsporidia, Nematocida parisii, which infects Caenorhabditis
      nematodes in the wild. We conducted a targeted RNAi screen for host C. elegans
      genes important for infection and growth of N. parisii, using nematode larval
      arrest as an assay for infection. Here, we present the results of this RNAi
      screen, and our analyses on one of the RNAi hits from the screen that was
      ultimately not corroborated by loss of function mutants. This hit was an RNAi
      clone against F56A8.3, a conserved gene that encodes a transmembrane protein
      containing leucine-rich repeats (LRRs), a domain found in numerous pathogen
      receptors from other systems. This RNAi clone caused C. elegans to be resistant
      to infection by N. parisii, leading to reduced larval arrest and lower pathogen
      load. Characterization of the endogenous F56A8.3 protein revealed that it is
      expressed in the intestine, localized to the membrane around lysosome-related
      organelles (LROs), and exists in two different protein isoforms in C. elegans. We
      used the CRISPR-Cas9 system to edit the F56A8.3 locus and created both a
      frameshift mutant resulting in a truncated protein and a complete knockout
      mutant. Neither of these mutants was able to recapitulate the infection
      phenotypes of the RNAi clone, indicating that the RNAi-mediated phenotypes are
      due to an off-target effect of the RNAi clone. Nevertheless, this study describes
      microsporidia-induced developmental arrest in C. elegans, presents results from
      an RNAi screen for host genes important for microsporidian infection, and
      characterizes aspects of the conserved F56A8.3 gene and its protein product. 

PMID- 25874558
TI  - Assessing depression related severity and functional impairment: the Overall
      Depression Severity and Impairment Scale (ODSIS).
AB  - BACKGROUND: The Overall Depression Severity and Impairment Scale (ODSIS) is a
      brief, five-item measure for assessing the frequency and intensity of depressive
      symptoms, as well as functional impairments in pleasurable activities, work or
      school, and interpersonal relationships due to depression. Although this scale is
      expected to be useful in various psychiatric and mental health settings, the
      reliability, validity, and interpretability have not yet been fully examined.
      This study was designed to examine the reliability, factorial, convergent, and
      discriminant validity of a Japanese version of the ODSIS, as well as its ability
      to distinguish between individuals with and without a major depressive disorder
      diagnosis. METHODS: From a pool of registrants at an internet survey company,
      2830 non-clinical and clinical participants were selected randomly (619 with
      major depressive disorder, 619 with panic disorder, 576 with social anxiety
      disorder, 645 with obsessive-compulsive disorder, and 371 non-clinical
      panelists). Participants were asked to respond to the ODSIS and conventional
      measures of depression, functional impairment, anxiety, neuroticism, satisfaction
      with life, and emotion regulation. RESULTS: Exploratory and confirmatory factor
      analysis of three split subsamples indicated the unidimensional factor structure
      of ODSIS. Multi-group confirmatory factor analysis showed invariance of factor
      loadings between non-clinical and clinical subsamples. The ODSIS also showed
      excellent internal consistency and test-retest intraclass correlation
      coefficients. Convergence and discriminance of the ODSIS with various measures
      were in line with our expectations. Receiver operating characteristic curve
      analyses showed that the ODSIS was able to detect a major depressive syndrome
      accurately. CONCLUSIONS: This study supports the reliability and validity of
      ODSIS in a non-western population, which can be interpreted as demonstrating
      cross-cultural validity.

PMID- 25874559
TI  - Pertussis in infants less than 6 months of age and household contacts, Italy,
      April 2014.
AB  - We report pertussis cases in 4 infants less than 6 months admitted with symptoms
      compatible with pertussis to the intensive care unit of the Universita Cattolica
      del Sacro Cuore in Rome, April 2014. Realtime PCR confirmed pertussis diagnosis
      for the 4 infants, 2 of them were cousins, and for the household contacts of 1 of
      them. Analysis of pertussis toxin, its promoter and pertactin was also performed.
      First of all, this report emphasizes the need to investigate household contact of
      infants with pertussis; secondly, to evaluate the selective vaccination of
      household members of newborns as an effective program to reduce pertussis in
      infants.

PMID- 25874560
TI  - Optimal placement of unified power flow controllers to improve dynamic voltage
      stability using power system variable based voltage stability indices.
AB  - This study examines a new approach to selecting the locations of unified power
      flow controllers (UPFCs) in power system networks based on a dynamic analysis of
      voltage stability. Power system voltage stability indices (VSIs) including the
      line stability index (LQP), the voltage collapse proximity indicator (VCPI), and
      the line stability index (Lmn) are employed to identify the most suitable
      locations in the system for UPFCs. In this study, the locations of the UPFCs are
      identified by dynamically varying the loads across all of the load buses to
      represent actual power system conditions. Simulations were conducted in a power
      system computer-aided design (PSCAD) software using the IEEE 14-bus and 39- bus
      benchmark power system models. The simulation results demonstrate the
      effectiveness of the proposed method. When the UPFCs are placed in the locations
      obtained with the new approach, the voltage stability improves. A comparison of
      the steady-state VSIs resulting from the UPFCs placed in the locations obtained
      with the new approach and with particle swarm optimization (PSO) and differential
      evolution (DE), which are static methods, is presented. In all cases, the UPFC
      locations given by the proposed approach result in better voltage stability than
      those obtained with the other approaches. 

PMID- 25874561
TI  - Smoking affects treatment outcome in patients with resected esophageal squamous
      cell carcinoma who received chemotherapy.
AB  - BACKGROUND: Cigarette smoking is reported to decrease survival and induce
      chemotherapy resistance in patients with various cancers. However, the impact of
      cigarette smoking on patients with esophageal squamous cell carcinoma (ESCC)
      remains unknown. METHODS: A total of 1,084 ESCC patients were retrospectively
      enrolled from a southern Chinese institution. Patients were divided into two
      groups according to their treatment modalities: the SC group (surgery with
      chemotherapy) (n = 306) and the S group (surgery without chemotherapy) (n = 778).
      Smoking status was quantified as smoking history (non-smoker, ex-smoker, and
      current smoker) and cumulative smoking (0, between 0 and 20, and greater than 20
      pack-years). The association between cigarette smoking and overall survival (OS)
      was evaluated using the Kaplan-Meier method and univariate/multivariate
      regression analysis. RESULTS: Among 1,084 patients, 702 (64.8%) reported a
      cigarette smoking history, and the 5-year OS for non-smokers and smokers was
      45.8% and 37.3%, respectively. In the SC group, compared with non-smoker, the
      adjusted HRs of ex-smoker and current smoker were 1.540 (95% CI, 1.1-2.2) and
      2.110 (95% CI, 1.4-3.1), respectively; there is a correlative trend of decreased
      OS with increased cigarette smoking (Ptrend = 0.001). These associations were
      insignificant in the S group. In subgroup analysis of the SC group, the lower OS
      conferred by smoking was not significantly modified by age, gender, body mass
      index, alcohol drinking, or chemotherapy method (chemotherapy and
      chemoradiotherapy). CONCLUSION: Our results suggest that smoking may affect
      treatment outcome in patients with resected ESCC who received chemotherapy.

PMID- 25874562
TI  - Meta-analysis of dexmedetomidine on emergence agitation and recovery profiles in
      children after sevoflurane anesthesia: different administration and different
      dosage.
AB  - The objective of this article is to evaluate the effect of dexmedetomidine on
      emergence agitation (EA) and recovery profiles in children after sevoflurane
      anesthesia and its pharmacological mechanisms. Standard bibliographic databases,
      including MEDLINE, EMBASE, PsycINFP, Springer and ISI Web of Knowledge, were
      artificially searched to identify all randomized controlled trials (RCTs)
      comparing the impact of dexmedetomidine with placebo, fentanyl and midazolam on
      EA and recovery profiles after sevoflurane anesthesia in post-anesthesia care
      unit (PACU). Two authors assessed the quality of each study independently in
      accordance with strict inclusion criteria and extracted data. RevMan 5.0 software
      was applied for performing statistic analysis. The outcomes analyzed included: 1)
      incidence of EA, 2) emergence time, 3) time to extubation, 4) incidence of post
      operation nausea and vomiting, 5) number of patients requiring an analgesic, and
      6) time to discharge from PACU. A total of 1364 patients (696 in the
      dexmedetomidine group and 668 in the placebo, fentanyl and midazolam group) from
      20 prospective RCTs were included in the meta-analysis. Compared with placebo,
      dexmedetomidine decreased the incidence of EA (risk ratio [RR] 0.37; 95% CI 0.30
      to 0.46), incidence of nausea and vomiting (RR 0.57; 95% CI 0.38 to 0.85) and
      number of patients requiring an analgesic (RR 0.43; 95% CI 0.31 to 0.59).
      However, dexmedetomidine had a significantly delayed effect on the emergence time
      (weighted mean differences [WMD] 1.16; 95% CI 0.72 to 1.60), time to extubation
      (WMD 0.61; 95% CI 0.27 to 0.95), and time to discharge from recovery room (WMD
      2.67; 95% CI 0.95 to 4.39). Compared with fentanyl (RR 1.39; 95% CI 0.78 to 2.48)
      and midazolam (RR 1.12; 95% CI 0.54 to 2.35), dexmedetomidine has no
      significantly difference on the incidence of EA. However, the analgesia effect of
      dexmedetomidine on postoperation pain has no significantly statistical
      differences compared with fentanyl (RR 1.12; 95% CI 0.66 to 1.91), which implied
      that its analgesia effect might play an important role in decreasing the incident
      of EA. No evidence of publication bias was observed. 

PMID- 25874563
TI  - Plants probiotics as a tool to produce highly functional fruits: the case of
      phyllobacterium and vitamin C in strawberries.
AB  - The increasing interest in the preservation of the environment and the health of
      consumers is changing production methods and food consumption habits. Functional
      foods are increasingly demanded by consumers because they contain bioactive
      compounds involved in health protection. In this sense biofertilization using
      plant probiotics is a reliable alternative to the use of chemical fertilizers,
      but there are few studies about the effects of plant probiotics on the yield of
      functional fruits and, especially, on the content of bioactive compounds. In the
      present work we reported that a strain of genus Phyllobacterium able to produce
      biofilms and to colonize strawberry roots is able to increase the yield and
      quality of strawberry plants. In addition, the fruits from plants inoculated with
      this strain have significantly higher content in vitamin C, one of the most
      interesting bioactive compounds in strawberries. Therefore the use of selected
      plant probiotics benefits the environment and human health without agronomical
      losses, allowing the production of highly functional foods. 

PMID- 25874564
TI  - Human electroretinal responses to grating patterns and defocus changes by global
      flash multifocal electroretinogram.
AB  - The electrical response of the retina was examined as a function of retinal
      region, using stimuli of various spatial frequencies in the first experiment. In
      the second experiment, the regional response of the retina to defocus at high and
      low spatial frequencies was investigated. Twenty three subjects were recruited
      for global flash multifocal electroretinogram (mfERG) in experiment 1. Black and
      white gratings (printed on plastic transparent sheets) of four spatial
      frequencies (SF), 0.24, 1.2, 2.4 and 4.8 cycle per degree were presented in front
      of the mfERG stimulation. The amplitudes and implicit times of the direct (DC)
      and induced (IC) components of mfERG responses were pooled into six concentric
      rings for analysis. There was low amplitude DC at low SF, which increased with
      increasing SF, and which decreased with increasing eccentricity. The IC was high
      in amplitude at all SF and reduced in amplitude with increasing eccentricity. Our
      findings suggested that outer and inner retina had different characteristics in
      processing spatial details. In experiment 2, Twenty-three young adults were
      recruited for mfERG measurement. The retinal electrical responses for low
      (0.24cpd) and high (4.8cpd) SF under fully corrected conditions of short-term
      negative defocus (-2D) and short term positive defocus (+2D) conditions were
      measured. There was a sign-dependent response to defocus in the DC response,
      mainly in peripheral regions. The sign dependent response at low SF was more
      obvious than that at high SF, and was located more peripherally. The IC response
      showed no clear trends for either defocus condition. The human retina seems to
      have a decoding system for optical defocus, which was tuned for low spatial
      frequency, and was located in the retinal near periphery. 

PMID- 25874565
TI  - Age-related nuclear translocation of P2X6 subunit modifies splicing activity
      interacting with splicing factor 3A1.
AB  - P2X receptors are ligand-gated ion channels sensitive to extracellular
      nucleotides formed by the assembling of three equal or different P2X subunits. In
      this work we report, for the first time, the accumulation of the P2X6 subunit
      inside the nucleus of hippocampal neurons in an age-dependent way. This location
      is favored by its anchorage to endoplasmic reticulum through its N-terminal
      domain. The extracellular domain of P2X6 subunit is the key to reach the nucleus,
      where it presents a speckled distribution pattern and is retained by interaction
      with the nuclear envelope protein spectrin alpha2. The in vivo results showed
      that, once inside the nucleus, P2X6 subunit interacts with the splicing factor
      3A1, which ultimately results in a reduction of the mRNA splicing activity. Our
      data provide new insights into post-transcriptional regulation of mRNA splicing,
      describing a novel mechanism that could explain why this process is sensitive to
      changes that occur with age. 

PMID- 25874566
TI  - A 90-day toxicology study of meat from genetically modified sheep overexpressing
      TLR4 in Sprague-Dawley rats.
AB  - Genetic modification offers alternative strategies to traditional animal
      breeding. However, the food safety of genetically modified (GM) animals has
      attracted increasing levels of concern. In this study, we produced GM sheep
      overexpressing TLR4, and the transgene-positive offsprings (F1) were confirmed
      using the polymerase chain reaction (PCR) and Southern blot. The expression of
      TLR4 was 2.5-fold compared with that of the wild-type (WT) sheep samples. During
      the 90-day safety study, Sprague-Dawley rats were fed with three different
      dietary concentrations (3.75%, 7.5%, and 15% wt/wt) of GM sheep meat, WT sheep
      meat or a commercial diet (CD). Blood samples from the rats were collected and
      analyzed for hematological and biochemical parameters, and then compared with
      hematological and biochemical reference ranges. Despite a few significant
      differences among the three groups in some parameters, all other values remained
      within the normal reference intervals and thus were not considered to be affected
      by the treatment. No adverse diet-related differences in body weights or relative
      organ weights were observed. Furthermore, no differences were observed in the
      gross necropsy findings or microscopic pathology of the rats whose diets
      contained the GM sheep meat compared with rats whose diets contained the WT sheep
      meat. Therefore, the present 90-day rat feeding study suggested that the meat of
      GM sheep overexpressing TLR4 had no adverse effect on Sprague-Dawley rats in
      comparison with WT sheep meat. These results provide valuable information
      regarding the safety assessment of meat derived from GM animals. 

PMID- 25874567
TI  - Expression of leukosialin (CD43) defines a major intrahepatic T cell subset
      associated with protective responses in visceral leishmaniasis.
AB  - BACKGROUND: Leishmaniasis is a neglected vector-borne tropical disease caused by
      Leishmania protozoa that are transmitted to mammalian hosts by infected sand
      flies. Infection is associated with distinct clinical manifestations that include
      cutaneous, mucocutaneous and visceral lesions. Visceral leishmaniasis (VL) is the
      most severe form of the disease and is considered second in terms of mortality
      and fourth in terms of morbidity among tropical diseases. IFN-gamma-producing T
      cells are involved in protection against the disease. METHODS: CD43+/+ and CD43-/
      mice on a C57BL/6 background were intravenously injected with 5 * 10 7
      amastigotes of Leishmania (L.) infantum chagasi, and 30 days after infection the
      clinical signs of disease were examined; the splenocytes were isolated and
      assayed for cytokine production; and the livers were removed for phenotypic
      analysis of T cell subsets by flow cytometry. RESULTS: We report that mice
      lacking CD43 display increased susceptibility to infection by Leishmania (L.)
      infantum chagasi, with higher parasite burdens than wild-type mice. The increased
      susceptibility of CD43-/- mice were associated with a weakened delayed
      hypersensitivity response and reduced levels of IgG2a antibodies to leishmania
      antigens. We further showed that expression of CD43 defines a major intrahepatic
      CD4+ and CD8+ T cell subsets with pro-inflammatory phenotypes and leads to
      increased levels of IFN-gamma secretion by activated splenocytes. CONCLUSIONS:
      Our findings point to a role of CD43 in the development of host resistance to
      visceral leishmaniasis.

PMID- 25874568
TI  - Free radical scavenging activity and comparative metabolic profiling of in vitro
      cultured and field grown Withania somnifera roots.
AB  - Free radical scavenging activity (FRSA), total phenolic content (TPC), and total
      flavonoid content (TFC) of in vitro cultured and field grown Withania somnifera
      (Ashwagandha) roots were investigated. Withanolides analysis and comprehensive
      metabolic profiling between 100% methanol extracts of in vitro and field grown
      root tissues was performed using high performance thin layer chromatography
      (HPTLC) and gas chromatography-mass spectrometry (GC-MS), respectively.
      Significantly higher levels of FRSA, TPC, and TFC were observed in in-vitro
      cultured roots compared with field grown samples. In addition, 30 day-cultured in
      vitro root samples (1 MIR) exhibited a significantly higher FRSA (IC50 81.01
      MUg/mL), TPC (118.91 mg GAE/g), and TFC (32.68 mg CE/g) compared with those in 45
      day-cultured samples (1.5 MIR). Total of 29 metabolites were identified in in
      vitro cultured and field grown roots by GC-MS analysis. The metabolites included
      alcohols, organic acids, purine, pyrimidine, sugars, and putrescine. Vanillic
      acid was only observed in the in vitro cultured root samples, and higher level of
      the vanillic acid was observed in 1 MIR when compared to 1.5 MIR. Therefore, it
      is suggested that 1 MIR might serve as an alternative to field grown roots for
      the development of medicinal and functional food products.

PMID- 25874570
TI  - Thinking about the future can cause forgetting of the past.
AB  - People are able to imagine events in the future that have not yet happened, an
      ability referred to as episodic future thinking. There is now compelling evidence
      that episodic future thinking is accomplished via processes similar to those that
      underlie episodic retrieval. Drawing upon work on retrieval-induced forgetting,
      which has shown that retrieving some items in memory can cause the forgetting of
      other items in memory, we show that engaging in episodic future thinking can
      cause related autobiographical memories (Experiments 1-3) and episodic event
      descriptions (Experiments 3-4) to become less recallable in the future than they
      would have been otherwise. This finding suggests that episodic future thinking
      can serve as a memory modifier by changing the extent to which memories from our
      past can be subsequently retrieved. 

PMID- 25874569
TI  - Sex, body mass index, and dietary fiber intake influence the human gut
      microbiome.
AB  - Increasing evidence suggests that the composition of the human gut microbiome is
      important in the etiology of human diseases; however, the personal factors that
      influence the gut microbiome composition are poorly characterized. Animal models
      point to sex hormone-related differentials in microbiome composition. In this
      study, we investigated the relationship of sex, body mass index (BMI) and dietary
      fiber intake with the gut microbiome in 82 humans. We sequenced fecal 16S rRNA
      genes by 454 FLX technology, then clustered and classified the reads to microbial
      genomes using the QIIME pipeline. Relationships of sex, BMI, and fiber intake
      with overall gut microbiome composition and specific taxon abundances were
      assessed by permutational MANOVA and multivariate logistic regression,
      respectively. We found that sex was associated with the gut microbiome
      composition overall (p=0.001). The gut microbiome in women was characterized by a
      lower abundance of Bacteroidetes (p=0.03). BMI (>25 kg/m2 vs. <25 kg/m2) was
      associated with the gut microbiome composition overall (p=0.05), and this
      relationship was strong in women (p=0.03) but not in men (p=0.29). Fiber from
      beans and from fruits and vegetables were associated, respectively, with greater
      abundance of Actinobacteria (p=0.006 and false discovery rate adjusted q=0.05)
      and Clostridia (p=0.009 and false discovery rate adjusted q=0.09). Our findings
      suggest that sex, BMI, and dietary fiber contribute to shaping the gut microbiome
      in humans. Better understanding of these relationships may have significant
      implications for gastrointestinal health and disease prevention. 

PMID- 25874571
TI  - Fusarinine C, a novel siderophore-based bifunctional chelator for radiolabeling
      with Gallium-68.
AB  - Fusarinine C (FSC), a siderophore-based chelator coupled with the model peptide
      c(RGDfK) (FSC(succ-RGD)3), revealed excellent targeting properties in vivo using
      positron emission tomography (PET). Here, we report the details of radiolabeling
      conditions and specific activity as well as selectivity for (68)Ga. (68)Ga
      labeling of FSC(succ-RGD)3 was optimized regarding peptide concentration, pH,
      temperature, reaction time, and buffer system. Specific activity (SA) of
      [(68)Ga]FSC(succ-RGD)3 was compared with (68)Ga-1,4,7-triazacyclononane, 1
      glutaric acid-4,7 acetic acid RGD ([(68)Ga]NODAGA-RGD). Stability was evaluated
      in 1000-fold ethylenediaminetetraacetic acid (EDTA) solution (pH 7) and phosphate
      buffered saline (PBS). Metal competition tests (Fe, Cu, Zn, Al, and Ni) were
      carried out using [(68)Ga]-triacetylfusarinine C. High radiochemical yield was
      achieved within 5 min at room temperature, in particular allowing labeling with
      (68)Ga up to pH 8 with excellent stability in 1000-fold EDTA solution and PBS.
      The 10-fold to 20-fold lower concentrations of FSC(succ-RGD)3 led to the same
      radiochemical yield compared with [(68)Ga]NODAGA-RGD with SA up to 1.8 TBq/umol.
      Metal competition tests showed high selective binding of (68)Ga to FSC. FSC is a
      multivalent siderophore-based bifunctional chelator allowing fast and highly
      selective labeling with (68)Ga in a wide pH range and results in stable complexes
      with high SA. Thus it is exceptionally well suited for the development of new
      (68)Ga-tracers for in vivo molecular imaging with PET.

PMID- 25874572
TI  - Molecular dynamics simulation reveals insights into the mechanism of unfolding by
      the A130T/V mutations within the MID1 zinc-binding Bbox1 domain.
AB  - The zinc-binding Bbox1 domain in protein MID1, a member of the TRIM family of
      proteins, facilitates the ubiquitination of the catalytic subunit of protein
      phosphatase 2A and alpha4, a protein regulator of PP2A. The natural mutation of
      residue A130 to a valine or threonine disrupts substrate recognition and
      catalysis. While NMR data revealed the A130T mutant Bbox1 domain failed to
      coordinate both structurally essential zinc ions and resulted in an unfolded
      structure, the unfolding mechanism is unknown. Principle component analysis
      revealed that residue A130 served as a hinge point between the structured beta
      strand-turn-beta-strand (beta-turn-beta) and the lasso-like loop sub-structures
      that constitute loop1 of the betabetaalpha-RING fold that the Bbox1 domain
      adopts. Backbone RMSD data indicate significant flexibility and departure from
      the native structure within the first 5 ns of the molecular dynamics (MD)
      simulation for the A130V mutant (>6 A) and after 30 ns for A130T mutant (>6 A).
      Overall RMSF values were higher for the mutant structures and showed increased
      flexibility around residues 125 and 155, regions with zinc-coordinating residues.
      Simulated pKa values of the sulfhydryl group of C142 located near A130 suggested
      an increased in value to ~9.0, paralleling the increase in the apparent
      dielectric constants for the small cavity near residue A130. Protonation of the
      sulfhydryl group would disrupt zinc-coordination, directly contributing to
      unfolding of the Bbox1. Together, the increased motion of residues of loop 1,
      which contains four of the six zinc-binding cysteine residues, and the increased
      pKa of C142 could destabilize the structure of the zinc-coordinating residues and
      contribute to the unfolding. 

PMID- 25874573
TI  - A New Approach for Fabricating Collagen/ECM-Based Bioinks Using Preosteoblasts
      and Human Adipose Stem Cells.
AB  - Cell-printing methods have been used widely in tissue regeneration because they
      enable fabricating biomimetic 3D structures laden with various cells. To achieve
      a cell-matrix block, various natural hydrogels that are nontoxic, biocompatible,
      and printable have been combined to obtain "bioinks." Unfortunately, most
      bioinks, including those with alginates, show low cell-activating properties.
      Here, a strategy for obtaining highly bioactive ink, which consisted of
      collagen/extracellular matrix (ECM) and alginate, for printing 3D porous cell
      blocks is developed. An in vitro assessment of the 3D porous structures laden
      with preosteoblasts and human adipose stem cells (hASCs) demonstrates that the
      cells in the bioinks are viable. Osteogenic activities with the designed bioinks
      show much higher levels than with the "conventional" alginate-based bioink.
      Furthermore, the hepatogenic differentiation ability of hASCs with the bioink is
      evaluated using the liver-specific genes, albumin, and TDO2, under hepatogenic
      differentiation conditions. The genes are activated within the 3D cell block
      fabricated using the new bioink. These results demonstrate that the 3D cell-laden
      structure fabricated using collagen/ECM-based bioinks can provide a novel
      platform for various tissue engineering applications. 

PMID- 25874574
TI  - Simvastatin modulates mesenchymal stromal cell proliferation and gene expression.
AB  - Statins are widely used hypocholesterolemic drugs that block the mevalonate
      pathway, responsible for the biosysnthesis of cholesterol. However, statins also
      have pleiotropic effects that interfere with several signaling pathways.
      Mesenchymal stromal cells (MSC) are a heterogeneous mixture of cells that can be
      isolated from a variety of tissues and are identified by the expression of a
      panel of surface markers and by their ability to differentiate in vitro into
      osteocytes, adipocytes and chondrocytes. MSC were isolated from amniotic
      membranes and bone marrows and characterized based on ISCT (International Society
      for Cell Therapy) minimal criteria. Simvastatin-treated cells and controls were
      directly assayed by CFSE (Carboxyfluorescein diacetate succinimidyl ester)
      staining to assess their cell proliferation and their RNA was used for microarray
      analyses and quantitative PCR (qPCR). These MSC were also evaluated for their
      ability to inhibit PBMC (peripheral blood mononuclear cells) proliferation. We
      show here that simvastatin negatively modulates MSC proliferation in a dose
      dependent way and regulates the expression of proliferation-related genes.
      Importantly, we observed that simvastatin increased the percentage of a subset of
      smaller MSC, which also were actively proliferating. The association of MSC
      decreased size with increased pluripotency and the accumulating evidence that
      statins may prevent cellular senescence led us to hypothesize that simvastatin
      induces a smaller subpopulation that may have increased ability to maintain the
      entire pool of MSC and also to protect them from cellular senescence induced by
      long-term cultures/passages in vitro. These results may be important to better
      understand the pleiotropic effects of statins and its effects on the biology of
      cells with regenerative potential. 

PMID- 25874575
TI  - Association Between Prolonged Graft Ischemia and Primary Graft Failure or
      Survival Following Lung Transplantation.
AB  - IMPORTANCE: The effect of prolonged graft ischemia (>=6 hours) on outcomes
      following lung transplantation is controversial. OBJECTIVE: To evaluate the
      effect of prolonged total graft ischemia times on long-term survival rates and
      the development of primary graft failure (PGF) following lung transplantation.
      DESIGN, SETTING, AND PARTICIPANTS: In this retrospective study, the United
      Network for Organ Sharing database was queried for adult patients who underwent
      lung transplantation from May 1, 2005, through December 31, 2011. Primary
      stratification by the presence of prolonged graft ischemia was performed. Kaplan
      Meier estimates at 1 and 5 years were used to compare survival in the 2 cohorts.
      A multivariable Cox proportional hazards regression model was constructed to
      identify predictors of 1- and 5-year mortality. A risk-adjusted predictive model
      for the development of PGF was formulated in a similar fashion. MAIN OUTCOMES AND
      MEASURES: The primary outcome of interest was 1- and 5-year survival. Secondary
      outcomes included PGF and other postoperative events, such as renal failure,
      biopsy-proven rejection, and stroke. RESULTS: Of the 10,225 patients who
      underwent lung transplantation, 3127 (30.6%) had allografts exposed to prolonged
      ischemia. There was no difference in survival at 1 (83.6% [95% CI, 82.3%-84.9%]
      vs 84.1% [95% CI, 83.3%-85.0%]; P = .41) or 5 (52.5% [95% CI, 51.0%-54.0%] vs
      53.5% [95% CI, 51.3%-55.6%]; P = .82) years between patients who received grafts
      that were or were not exposed to ischemia that lasted 6 hours or more,
      respectively. Prolonged graft ischemia did not independently predict 1- or 5-year
      mortality or the development of PGF (odds ratio, 1.11; 95% CI, 0.88-1.39; P =
      .37). Furthermore, prolonged ischemia did not independently predict 1-year
      (hazard ratio, 1.09; 95% CI, 0.97-1.22; P =.15) or 5-year (hazard ratio, 1.05;
      95% CI, 0.98-1.14; P =.18) mortality or the development of PGF (odds ratio, 1.11;
      95% CI, 0.88-1.39; P =.37). CONCLUSIONS AND RELEVANCE: No association was found
      between prolonged total graft ischemia times and primary graft failure or
      survival following lung transplantation. Given the scarcity of organs and the
      paucity of suitable recipients, prolonged ischemia time should not preclude
      transplantation. It is, therefore, reasonable to consider extending the accepted
      period of ischemia to more than 6 hours in certain patient populations to improve
      organ use.

PMID- 25874576
TI  - Gamma oscillations as a neural signature of shifting times in narrative language.
AB  - Verbs and other temporal expressions allow speakers to specify the location of
      events in time, as well as to move back and forth in time, shifting in a
      narrative between past, present and future. The referential flexibility of
      temporal expressions is well understood in linguistics but its neurocognitive
      bases remain unknown. We aimed at obtaining a neural signature of shifting times
      in narrative language. We recorded and analyzed event-related brain potentials
      (ERPs) and oscillatory responses to the adverb 'now' and to the second main verb
      in Punctual ('An hour ago the boy stole a candy and now he peeled the fruit') and
      Iterative ('The entire afternoon the boy stole candy and now he peeled the
      fruit') contexts. 'An hour ago' introduces a time frame that lies entirely in the
      past, 'now' shifts the narrative to the present, and 'peeled' shifts it back to
      the past. These two referential shifts in Punctual contexts are expected to leave
      very similar traces on neural responses. In contrast, 'The entire afternoon'
      specifies a time frame that may encompass past, present and future, such that
      both 'now' and 'peeled' are consistent with it. Here, no time shift is required.
      We found no difference in ERPs between Punctual and Iterative contexts either at
      'now' or at the second verb. However, reference shifts modulated oscillatory
      signals. 'Now' and the second verb in Punctual contexts resulted in similar
      responses: an increase in gamma power with a left-anterior distribution. Gamma
      bursts were absent in Iterative contexts. We propose that gamma oscillations here
      reflect the binding of temporal variables to the values allowed by constraints
      introduced by temporal expressions in discourse. 

PMID- 25874577
TI  - Acute tubulointerstitial nephritis due to large amount of sorrel (Rumex acetosa)
      intake.

PMID- 25874578
TI  - Treatment response to sleep, pain, and mood disturbance and their correlation
      with sleep disturbance in adult patients with moderate-to-severe primary restless
      legs syndrome: Pooled analyses from 3 trials of gabapentin enacarbil.
AB  - INTRODUCTION: This pooled analysis investigated the effects of gabapentin
      enacarbil (GEn) on clinical correlates of sleep disturbance in adults with
      moderate-to-severe primary restless legs syndrome (RLS) and no-to-moderate or
      severe-to-very severe baseline sleep disturbance. METHODS: Co-primary end-points
      were mean change from baseline to week 12 in International Restless Legs Scale
      (IRLS) total score and proportion of responders ('much'/'very much' improved) on
      the investigator-rated Clinical Global Impression-Improvement (CGI-I) scale (week
      12). Pain, mood, individual IRLS items, and safety were assessed. RESULTS: The
      modified intent-to-treat population was 671 adults randomized to GEn 600 mg (n =
      161), GEn 1200 mg (n = 266), or placebo (n = 244). GEn significantly improved
      least squares mean change in IRLS total score from baseline versus placebo for no
      to-moderate (GEn 600 mg,- 12.3; 1200 mg, - 11.3; placebo, - 7.7) and severe-to
      very severe (- 16.6; - 17.0; - 12.7) groups (all P < 0.01). Significantly more
      GEn-treated patients (both doses) were CGI-I responders (week 12) versus placebo
      in both sleep subgroups (all P < 0.01). GEn substantially improved mood and pain
      scores for both sleep subgroups versus placebo. The most frequent treatment
      emergent adverse events were somnolence and dizziness. CONCLUSION: GEn (600 mg
      and 1200 mg) was effective and well tolerated in adults with moderate-to-severe
      primary RLS regardless of baseline sleep disturbance level.

PMID- 25874579
TI  - Evaluating clinical trial designs for investigational treatments of Ebola virus
      disease.
AB  - BACKGROUND: Experimental treatments for Ebola virus disease (EVD) might reduce
      EVD mortality. There is uncertainty about the ability of different clinical trial
      designs to identify effective treatments, and about the feasibility of
      implementing individually randomised controlled trials during an Ebola epidemic.
      METHODS AND FINDINGS: A treatment evaluation programme for use in EVD was devised
      using a multi-stage approach (MSA) with two or three stages, including both non
      randomised and randomised elements. The probabilities of rightly or wrongly
      recommending the experimental treatment, the required sample size, and the
      consequences for epidemic outcomes over 100 d under two epidemic scenarios were
      compared for the MSA, a sequential randomised controlled trial (SRCT) with up to
      20 interim analyses, and, as a reference case, a conventional randomised
      controlled trial (RCT) without interim analyses. Assuming 50% 14-d survival in
      the population treated with the current standard of supportive care, all designs
      had similar probabilities of identifying effective treatments correctly, while
      the MSA was less likely to recommend treatments that were ineffective. The MSA
      led to a smaller number of cases receiving ineffective treatments and faster roll
      out of highly effective treatments. For less effective treatments, the MSA had a
      high probability of including an RCT component, leading to a somewhat longer time
      to roll-out or rejection. Assuming 100 new EVD cases per day, the MSA led to
      between 6% and 15% greater reductions in epidemic mortality over the first 100 d
      for highly effective treatments compared to the SRCT. Both the MSA and SRCT led
      to substantially fewer deaths than a conventional RCT if the tested interventions
      were either highly effective or harmful. In the proposed MSA, the major threat to
      the validity of the results of the non-randomised components is that referral
      patterns, standard of care, or the virus itself may change during the study
      period in ways that affect mortality. Adverse events are also harder to quantify
      without a concurrent control group. CONCLUSIONS: The MSA discards ineffective
      treatments quickly, while reliably providing evidence concerning effective
      treatments. The MSA is appropriate for the clinical evaluation of EVD treatments.

PMID- 25874580
TI  - Methiopropamine in blood samples from drivers suspected of being under the
      influence of drugs.
AB  - OBJECTIVES: Methiopropamine (MPA; 1-(thiophen-2-yl)-2-methylaminopropane) belongs
      to the new psychoactive substances (NPS) that have emerged on the drug market in
      recent years. MPA appeared in 2011 and is an analogue of methamphetamine, sold
      as, for example, "Slush Eric" and "Blow." It is reported to have effects similar
      to those of methamphetamine, but the toxicity in humans is not known. Three fatal
      cases involving MPA have been reported. One analytical confirmed intoxication
      case has been published, and this supports the symptoms described by the users.
      The prevalence of recreational use of MPA is unknown, and no studies have
      reported the prevalence in driving under the influence of drug (DUID) cases.
      METHODS: We investigated the frequency of MPA in DUID cases received at our
      institute during a 12-week period and report the analytical method using an
      ultraperformance liquid chromatography.tandem mass spectrometry for
      quantification of MPA in whole blood. The analytical findings were compared to
      the results from a clinical test of impairment performed by a physician shortly
      after the driving episode. The samples were analyzed for 42 different
      psychoactive substances. RESULTS: MPA was detected in 10 DUID cases (0.8% of the
      cases), only from male drivers. Other drugs were detected concomitantly in all
      the cases. Two of the cases were traffic accidents. CONCLUSIONS: Our study shows
      that MPA is found in DUID cases and reveals that NPS are used among drivers and
      also proven in blood from drivers involved in traffic accidents. More studies are
      requested regarding the pharmacological and toxicological effects of MPA and
      other NPS. This is the first article that describes a method for analyzing and
      quantifying MPA in whole blood samples.

PMID- 25874581
TI  - Incorporating linguistic knowledge for learning distributed word representations.
AB  - Combined with neural language models, distributed word representations achieve
      significant advantages in computational linguistics and text mining. Most
      existing models estimate distributed word vectors from large-scale data in an
      unsupervised fashion, which, however, do not take rich linguistic knowledge into
      consideration. Linguistic knowledge can be represented as either link-based
      knowledge or preference-based knowledge, and we propose knowledge regularized
      word representation models (KRWR) to incorporate these prior knowledge for
      learning distributed word representations. Experiment results demonstrate that
      our estimated word representation achieves better performance in task of semantic
      relatedness ranking. This indicates that our methods can efficiently encode both
      prior knowledge from knowledge bases and statistical knowledge from large-scale
      text corpora into a unified word representation model, which will benefit many
      tasks in text mining. 

PMID- 25874582
TI  - Correction: BILBO1 is a scaffold protein of the flagellar pocket collar in the
      pathogen Trypanosoma brucei.
AB  - [This corrects the article DOI: 10.1371/journal.ppat.1004654.]. 

PMID- 25874583
TI  - Effect of slurry ice on the functional properties of proteins related to quality
      loss during skipjack tuna (Katsuwonus pelamis) chilled storage.
AB  - The effect of slurry ice on the quality of Skipjack tuna (Katsuwonus pelamis)
      during chilling storage was investigated and compared to flake ice. Slurry ice
      treated samples showed significantly higher springiness and chewiness variables
      than the blank and flake ice-treated samples (P < 0.05). The growth of
      microorganisms in tuna muscle treated with slurry ice was also down significantly
      (P < 0.05), and the total aerobic counts didn't reach higher scores than 5.0 log
      CFU/g during the whole chilling storage. Additionally, the myofibrillar protein,
      Ca(2+)-ATPase activity, and total sulfydryl (SH) content in muscle treated with
      slurry ice were all significantly higher than the blank and flake-iced samples (P
      < 0.05). This was probably due to the faster cooling, subzero final-temperature,
      and larger heat exchange derived from slurry ice. Standard error of mean and
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis results also confirmed
      that slurry ice treatment could effectively retard the degradation of
      myofibrillar proteins and showed a positive effect on the stability of tissue
      structures. 

PMID- 25874584
TI  - Should we search Chinese biomedical databases when performing systematic reviews?
AB  - BACKGROUND: Chinese biomedical databases contain a large number of publications
      available to systematic reviewers, but it is unclear whether they are used for
      synthesizing the available evidence. METHODS: We report a case of two systematic
      reviews on the accuracy of anti-cyclic citrullinated peptide for diagnosing
      rheumatoid arthritis. In one of these, the authors did not search Chinese
      databases; in the other, they did. We additionally assessed the extent to which
      Cochrane reviewers have searched Chinese databases in a systematic overview of
      the Cochrane Library (inception to 2014). RESULTS: The two diagnostic reviews
      included a total of 269 unique studies, but only 4 studies were included in both
      reviews. The first review included five studies published in the Chinese language
      (out of 151) while the second included 114 (out of 118). The summary accuracy
      estimates from the two reviews were comparable. Only 243 of the published 8,680
      Cochrane reviews (less than 3%) searched one or more of the five major Chinese
      databases. These Chinese databases index about 2,500 journals, of which less than
      6% are also indexed in MEDLINE. All 243 Cochrane reviews evaluated an
      intervention, 179 (74%) had at least one author with a Chinese affiliation; 118
      (49%) addressed a topic in complementary or alternative medicine. DISCUSSION AND
      CONCLUSIONS: Although searching Chinese databases may lead to the identification
      of a large amount of additional clinical evidence, Cochrane reviewers have rarely
      included them in their search strategy. We encourage future initiatives to
      evaluate more systematically the relevance of searching Chinese databases, as
      well as collaborative efforts to allow better incorporation of Chinese resources
      in systematic reviews.

PMID- 25874586
TI  - Effect of capillary and marangoni forces on transport phenomena in microgravity.
AB  - The Constrained Vapor Bubble (CVB) experiment concerns a transparent, simple,
      "wickless" heat pipe operated in the microgravity environment of the
      International Space Station (ISS). In a microgravity environment, the relative
      effect of Marangoni flow is amplified because of highly reduced buoyancy driven
      flows as demonstrated herein. In this work, experimental results obtained using a
      transparent 30 mm long CVB module, 3 mm * 3 mm in square cross-section, with
      power inputs of up to 3.125 W are presented and discussed. Due to the extremely
      low Bond number and the dielectric materials of construction, the CVB system was
      ideally suited to determining if dry-out as a result of Marangoni forces might
      contribute to limiting heat pipe performance and exactly how that limitation
      occurs. Using a combination of visual observations and thermal measurements, we
      find a more complicated phenomenon in which opposing Marangoni and capillary
      forces lead to flooding of the device. A simple one-dimensional, thermal-fluid
      flow model describes the essence of the relative importance of the two stresses.
      Moreover, even though the heater end of the device is flooded and the liquid is
      highly superheated, boiling does not occur due to high evaporation rates. 

PMID- 25874585
TI  - Direct Observation of Coupling between Structural Fluctuation and Ultrafast
      Hydration Dynamics of Fluorescent Probes in Anionic Micelles.
AB  - The coupling of structural fluctuation and the dynamics of associated water
      molecules of biological macromolecules is vital for various biological
      activities. Although a number of molecular dynamics (MD) studies on proteins/DNA
      predicted the importance of such coupling, experimental evidence of variation of
      hydration dynamics with controlled structural fluctuation even in model
      macromolecule is sparse and raised controversies in the contemporary literature.
      Here, we have investigated dynamics of hydration at the surfaces of two similar
      anionic micelles sodium dodecyl sulfate (SDS) and sodium dodecylbenzenesulfonate
      (SDBS) as model macromolecules using coumarin 500 (C500) as spectroscopic probe
      with femtosecond to picosecond time resolution up to 20 ns time window. The
      constituting surfactants SDS and SDBS are structurally similar except one benzene
      moiety in the SDBS may offer additional rigidity to the SDBS micelles through pi
      stacking and added bulkiness. The structural integrity of the micelles in the
      aqueous medium is confirmed in dynamic light scattering (DLS) studies. A variety
      of studies including polarization gated fluorescence spectroscopy and
      quasielastic neutron scattering (QENS) have been used to confirm differential
      structural fluctuation of SDS and SDBS micelles. We have also employed
      femtosecond-resolved Forster resonance energy transfer (FRET) in order to study
      binding of a cationic organic ligand ethidium bromide (EtBr) salt at the micellar
      surfaces. The distance distribution of the donor (C500)-acceptor (EtBr) in the
      micellar media reveals the manifestation of the structural flexibility of the
      micelles. Our studies on dynamical coupling of the structural flexibility with
      surface hydration in the nanoscopic micellar media may find the relevance in the
      "master-slave" type water dynamics in biologically relevant macromolecules. 

PMID- 25874587
TI  - Phosphorus recovery from pig manure solids prior to land application.
AB  - Land disposal of pig manure is an environmental concern due to an imbalance of
      the nitrogen to phosphorus (N:P) ratio for crop production, leading to excess
      phosphorus (P) in soils and potential risks of water pollution. A process called
      "quick wash" was investigated for its feasibility to extract and recover P from
      pig manure solids. This process consists of selective dissolution of P from solid
      manure into a liquid extract using mineral or organic acid solutions, and
      recovery of P from the liquid extract by adding lime and an organic polymer to
      form a P precipitate. Laboratory tests confirmed the quick wash process
      selectively removed and recovered up to 90% of the total (TP) from fresh pig
      manure solids while leaving significant amounts of nitrogen (N) in the washed
      manure residue. As a result of manure P extraction, the washed solid residue
      became environmentally safer for land application with a more balanced N:P ratio
      for crop production. The recovered P can be recycled and used as fertilizer for
      crop production while minimizing manure P losses into the environment. 

PMID- 25874588
TI  - Online participation in climate change adaptation: A case study of agricultural
      adaptation measures in Northern Italy.
AB  - The new EU strategy on adaptation to climate change suggests flexible and
      participatory approaches. Face-to-face contact, although it involves time
      consuming procedures with a limited audience, has often been considered the most
      effective participatory approach. In recent years, however, there has been an
      increase in the visibility of different citizens' initiatives in the online
      world, which strengthens the possibility of greater citizen agency. This paper
      investigates whether the Internet can ensure efficient public participation with
      meaningful engagement in climate change adaptation. In elucidating issues
      regarding climate change adaptation, we developed an eParticipation framework to
      explore adaptation capacity of agriculture to climate change in Northern Italy.
      Farmers were mobilised using a pre-existing online network. First they took part
      in an online questionnaire for revealing their perceptions of and reactions to
      the impacts of ongoing changes in agriculture. We used these results to suggest a
      portfolio of policy measures and to set evaluation criteria. Farmers then
      evaluated these policy options, using a multi criteria analysis tool with a
      simple user-friendly interface. Our results showed that eParticipation is
      efficient: it supports a rapid data collection, while involving high number of
      participants. Moreover, we demonstrated that the digital divide is decreasingly
      an obstacle for using online spaces for public engagement. This research does not
      present eParticipation as a panacea. Rather, eParticipation was implemented with
      well-established participatory approaches to both validate the results and,
      consequently, communicate meaningful messages on local agricultural adaptation
      practices to regional decision-makers. Feedbacks from the regional decision
      makers showed their interest in using eParticipation to improve communication
      with farmers in the future. We expect that, with further Internet proliferation,
      eParticipation may allow the inclusion of more representative samples, which
      would contribute to an informed and legitimate decision-making process. 

PMID- 25874589
TI  - Management of apical pelvic organ prolapse.
AB  - Pelvic organ prolapse is a prevalent condition, with up to 12 % of women
      requiring surgery in their lifetime. This manuscript reviews the treatment
      options for apical prolapse, specifically. Both conservative and surgical
      management options are acceptable and should be based on patient preferences.
      Pessaries are the most commonly used conservative management options. Guided
      pelvic floor muscle training is more beneficial than self-taught Kegel exercises,
      though may not be effective for high stage or apical prolapse. Surgical treatment
      options include abdominal and vaginal approaches, the latter of which can be
      performed open, laparoscopically, and robotically. A systematic review has
      demonstrated that sacrocolpopexy has better long-term success for treatment of
      apical prolapse than vaginal techniques, but vaginal surgery can be considered an
      acceptable alternative. Recent data has demonstrated equal efficacy between
      uterosacral ligament suspension and sacrospinous ligament suspension at 1 year.
      To date, two randomized controlled trials have demonstrated equal efficacy
      between robotic and laparoscopic sacrocolpopexy. Though abdominal approaches may
      have increased long-term durability, when counseling their patients, surgeons
      should consider longer operating times and increased pain and cost with these
      procedures compared to vaginal surgery. KEY POINTS: * Pelvic floor physical
      therapy (PFPT) with a physical therapist is the best approach to conservative
      management of apical prolapse [10]. * Pessaries should be managed with regular
      follow-up care to minimize complications [14*]. * Minimally invasive
      sacrocolpopexy appears as effective as the gold standard abdominal sacrocolpopexy
      (ASC) [42*]. * Robotic assisted sacrocolpopexy (RASC) and laparoscopic assisted
      sacrocolpopexy (LASC) are equally effective and should be utilized by pelvic
      floor surgeons based on their skill level and expertise in laparoscopy [44, 45*].
      * Uterosacral ligament suspension (USLS) and sacrospinous ligament suspension
      (SSLS) are considered equally effective procedures and can be combined with a
      vaginal hysterectomy. * Obliterative procedures are effective but are considered
      definitive surgery [24**]. * The use of transvaginal mesh has been shown in some
      studies to be superior to native tissue repairs with regard to anatomic outcomes,
      but complication rates are higher. Transvaginal mesh should be reserved for
      surgeons with adequate training so that complications are minimized.

PMID- 25874590
TI  - Effects of high temperature on the ultrastructure and microtubule organization of
      interphase and dividing cells of the seagrass Cymodocea nodosa.
AB  - Short-time temperature effects (34-40  degrees C) on microtubule (MT)
      organization and on cell structure of young epidermal leaf cells of the seagrass
      Cymodocea nodosa were investigated under laboratory conditions using transmission
      electron microscopy (TEM) and tubulin immunofluorescence. The interphase MT
      network was affected by the increased temperature, the effect being time
      dependent and expressed in both the form and the orientation of the MT bundles.
      After 1 h at 38  degrees C, there was also a severe disturbance in dividing cells
      with thick and short MTs in the mitotic spindle and atypically organized
      phragmoplasts, while after 2 h at 38  degrees C the mitotic index was tenfold
      reduced compared with the control material. After 6 h at 38  degrees C, a large
      number of telophase cells were observed, meaning that cytokinesis was blocked.
      TEM observation revealed cells with uncompleted cell plates consisting of swollen
      vesicles and branched cisternae, with no phragmoplast MTs. These cells bear a
      nucleolus with segregated fibrillar and granular zones, an increased number of
      swollen mitochondria, and numerous parallel arrays of endoplasmic reticulum
      cisternae in the cortical cytoplasm. The possible relationship of these changes
      in C. nodosa with a response mechanism in order to face elevated temperature
      effects of climate change is discussed.

PMID- 25874591
TI  - On the excitation of action potentials by protons and its potential implications
      for cholinergic transmission.
AB  - One of the most conserved mechanisms for transmission of a nerve pulse across a
      synapse relies on acetylcholine (ACh). Ever since the Nobel Prize-winning works
      of Dale and Loewi, it has been assumed that ACh-subsequent to its action on a
      postsynaptic cell-is split into inactive by-products by acetylcholinesterase
      (AChE). Herein, the widespread assumption of inactivity of ACh's hydrolysis
      products is falsified. Excitable cells (Chara braunii internodes), which had
      previously been unresponsive to ACh, became ACh-sensitive in the presence of
      AChE. The latter was evidenced by a striking difference in cell membrane
      depolarization upon exposure to 10 mM intact ACh (?V = -2 +/- 5 mV) and its
      hydrolysate (?V = 81 +/- 19 mV), respectively, for 60 s. This pronounced
      depolarization, which also triggered action potentials, was clearly attributed to
      one of the hydrolysis products: acetic acid (?V = 87 +/- 9 mV at pH 4.0; choline
      ineffective in the range 1-10 mM). In agreement with our findings, numerous
      studies in the literature have reported that acids excite gels, lipid membranes,
      plant cells, erythrocytes, as well as neurons. Whether excitation of the
      postsynaptic cell in a cholinergic synapse is due to protons or due to intact ACh
      is a most fundamental question that has not been addressed so far.

PMID- 25874593
TI  - Supramolecular assistance for the selective demethylation of calixarene-based
      receptors.
AB  - The selective demethylation of methoxy groups of several multifunctionalized
      1,3,5-trimethoxycalix[6]arene-based receptors has been achieved. It is shown in
      this study that the best reagent is trimethylsilyl iodide (TMSI) and that the
      conformation adopted by the calixarene core is crucial for both the selectivity
      and the efficiency of the process. A key feature appears to be the "in" or "out"
      orientation of the methoxy substituents relative to the macrocyclic cavity. If
      projected inward, the reaction is slow and not selective. If projected outward,
      the reaction is fast and selective. A strategy that consists of exploiting the
      host-guest properties of the receptors to change their conformation and to permit
      their selective demethylation has been developed. Four cases of such a
      supramolecular assistance are reported, demonstrating the efficiency of the
      strategy. Such an allosteric control is highly reminiscent of biological
      processes allowing selective transformation of multifunctional molecules. 

PMID- 25874592
TI  - A preliminary and qualitative study of resource ratio theory to nitrifying lab
      scale bioreactors.
AB  - The incorporation of microbial diversity in design would ideally require
      predictive theory that would relate operational parameters to the numbers and
      distribution of taxa. Resource ratio-theory (RRT) might be one such theory. Based
      on Monod kinetics, it explains diversity in function of resource-ratio and
      richness. However, to be usable in biological engineered system, the growth
      parameters of all the bacteria under consideration and the resource supply and
      diffusion parameters for all the relevant nutrients should be determined. This is
      challenging, but plausible, at least for low diversity groups with simple
      resource requirements like the ammonia oxidizing bacteria (AOB). One of the major
      successes of RRT was its ability to explain the 'paradox of enrichment' which
      states that diversity first increases and then decreases with resource richness.
      Here, we demonstrate that this pattern can be seen in lab-scale-activated sludge
      reactors and parallel simulations that incorporate the principles of RRT in a
      floc-based system. High and low ammonia and oxygen were supplied to continuous
      flow bioreactors with resource conditions correlating with the composition and
      diversity of resident AOB communities based on AOB 16S rDNA clone libraries.
      Neither the experimental work nor the simulations are definitive proof for the
      application of RRT in this context. However, it is sufficient evidence that such
      approach might work and justify a more rigorous investigation. 

PMID- 25874594
TI  - A Potent Systemically Active N-Acylethanolamine Acid Amidase Inhibitor that
      Suppresses Inflammation and Human Macrophage Activation.
AB  - Fatty acid ethanolamides such as palmitoylethanolamide (PEA) and
      oleoylethanolamide (OEA) are lipid-derived mediators that potently inhibit pain
      and inflammation by ligating type-alpha peroxisome proliferator-activated
      receptors (PPAR-alpha). These bioactive substances are preferentially degraded by
      the cysteine hydrolase, N-acylethanolamine acid amidase (NAAA), which is highly
      expressed in macrophages. Here, we describe a new class of beta-lactam
      derivatives that are potent, selective, and systemically active inhibitors of
      intracellular NAAA activity. The prototype of this class deactivates NAAA by
      covalently binding the enzyme's catalytic cysteine and exerts profound anti
      inflammatory effects in both mouse models and human macrophages. This agent may
      be used to probe the functions of NAAA in health and disease and as a starting
      point to discover better anti-inflammatory drugs. 

PMID- 25874595
TI  - Sedation practice and comfort during colonoscopy: lessons learnt from a national
      screening programme.
AB  - AIM: Medication may be used to manage discomfort during colonoscopy but practice
      varies. The relationship between medication use and comfort during colonoscopy
      was examined in the English Bowel Cancer Screening Programme. METHODS: Data
      related to patient comfort and medication use from all 113,316 examinations
      performed within the English Bowel Cancer Screening Programme between 1 January
      2010 and 31 December 2012 were analysed. Comfort was rated on the five-point
      Modified Gloucester Comfort Scale: 1, no discomfort; 5, severe discomfort. Scores
      of 4 and 5 were considered to indicate significant discomfort. Correlations
      between the proportion of examinations associated with significant discomfort and
      the amounts of medication used by colonoscopists were assessed using Spearman's
      rho. Logistic regression modelling examined the independent predictors of
      significant discomfort. RESULTS: Patients had a mean age of 65.7 years, and 58%
      were male. Examinations were performed by 290 endoscopists. In 91% of
      examinations, there was no significant discomfort reported during examination;
      however, there was considerable variation between individual colonoscopists
      (range 76.1-99.2%).Intravenous sedation and opiate analgesia were used during
      most examinations, but there was wide variation between colonoscopists, with a
      median (range) usage of 95.1% (4.1-100%) and 97.3% (5.6-100%), respectively.
      There was no association between the amount of sedation and analgesia used and
      significant discomfort (rho<0.2). On multivariate analysis, significant
      discomfort was found to be more common among female individuals [odds ratio
      (OR)=2.0], on incomplete examinations (OR=6.7), and among patients with
      diverticulosis (OR=1.4). CONCLUSION: There was wide variation in medication
      practice among English screening colonoscopists, but this was unrelated to the
      occurrence of significant discomfort.

PMID- 25874597
TI  - Relating structure and function of inner hair cell ribbon synapses.
AB  - In the mammalian cochlea, sound is encoded at synapses between inner hair cells
      (IHCs) and type I spiral ganglion neurons (SGNs). Each SGN receives input from a
      single IHC ribbon-type active zone (AZ) and yet SGNs indefatigably spike up to
      hundreds of Hz to encode acoustic stimuli with submillisecond precision.
      Accumulating evidence indicates a highly specialized molecular composition and
      structure of the presynapse, adapted to suit these high functional demands.
      However, we are only beginning to understand key features such as stimulus
      secretion coupling, exocytosis mechanisms, exo-endocytosis coupling, modes of
      endocytosis and vesicle reformation, as well as replenishment of the readily
      releasable pool. Relating structure and function has become an important avenue
      in addressing these points and has been applied to normal and genetically
      manipulated hair cell synapses. Here, we review some of the exciting new insights
      gained from recent studies of the molecular anatomy and physiology of IHC ribbon
      synapses. 

PMID- 25874601
TI  - Ammonia detection by using flexible Lewis acidic sites in luminescent porous
      frameworks constructed from a bipyridinium derivative.
AB  - A flexible bipyridinium ligand with Lewis acidic sites has been introduced into
      two isomorphous metal-organic frameworks to yield luminescent porous materials
      with subtriangular pore windows, which exhibit sensitive fluorescent response for
      ammonia molecules and can be proved at the molecular level by Raman spectroscopy.

PMID- 25874598
TI  - Risk factors for loss of residual renal function in children treated with chronic
      peritoneal dialysis.
AB  - In dialyzed patients, preservation of residual renal function is associated with
      better survival, lower morbidity, and greater quality of life. To analyze the
      evolution of residual diuresis over time, we prospectively monitored urine output
      in 401 pediatric patients in the global IPPN registry who commenced peritoneal
      dialysis (PD) with significant residual renal function. Associations of patient
      characteristics and time-variant covariates with daily urine output and the risk
      of developing oligoanuria (under 100 ml/m(2)/day) were analyzed by mixed linear
      modeling and Cox regression analysis including time-varying covariates. With an
      average loss of daily urine volume of 130 ml/m(2) per year, median time to
      oligoanuria was 48 months. Residual diuresis significantly subsided more rapidly
      in children with glomerulopathies, lower diuresis at start of PD, high
      ultrafiltration volume, and icodextrin use. Administration of diuretics
      significantly reduced oligoanuria risk, whereas the prescription of renin
      angiotensin system antagonists significantly increased the risk oligoanuria.
      Urine output on PD was significantly associated in a negative manner with
      glomerulopathies (-584 ml/m(2)) and marginally with the use of icodextrin (-179
      ml/m(2)) but positively associated with the use of biocompatible PD fluid (+111
      ml/m(2)). Children in both Asia and North America had consistently lower urine
      output compared with those in Europe perhaps due to regional variances in
      therapy. Thus, in children undergoing PD, residual renal function depends
      strongly on the cause of underlying kidney disease and may be modifiable by
      diuretic therapy, peritoneal ultrafiltration, and choice of PD fluid.

PMID- 25874600
TI  - Combined use of nonsteroidal anti-inflammatory drugs with diuretics and/or renin
      angiotensin system inhibitors in the community increases the risk of acute kidney
      injury.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with an increased
      risk of acute kidney injury (AKI) when used in triple combination with renin
      angiotensin system inhibitors and diuretics, but previous research reported that
      NSAIDs in dual combinations with either renin-angiotensin system inhibitors or
      diuretics alone were not. However, earlier studies relied on hospital coding to
      define AKI, which may underestimate true risk. This nested case-control study
      characterized the risk of community-acquired AKI associated with NSAID use among
      78,379 users of renin-angiotensin system inhibitors and/or diuretics, where AKI
      was defined as a 50% or greater increase in creatinine from baseline. The AKI
      incidence was 68/10,000 person-years. The relative increase in AKI risk was
      similar for NSAID use in both triple (adjusted rate ratio 1.64 (95% CI 1.25
      2.14)) and dual combinations with either renin-angiotensin system inhibitors
      (1.60 (1.18-2.17)) or diuretics (1.64 (1.17-2.29)). However, the absolute
      increase in AKI risk was higher for NSAIDs used in triple versus dual
      combinations with renin-angiotensin system inhibitors or diuretics alone (numbers
      needed to harm for 1 year treatment with NSAID of 158 vs. over 300). AKI risk was
      highest among users of loop diuretic/aldosterone antagonist combinations, in
      those over 75 years of age, and in those with renal impairment. Thus, the
      nephrotoxic potential of both dual and triple combinations of NSAIDs with renin
      angiotensin system inhibitors and/or diuretics yields a higher incidence of AKI
      than previously thought. 

PMID- 25874602
TI  - Colorimetric logic response based on aptamer functionalized colloidal crystal
      hydrogels.
AB  - A novel colorimetric logic system based on the aptamer-cross-linked colloidal
      crystal hydrogel (CCH) was developed. With the input stimuli of Hg(2+) and Ag(+),
      the CCH displayed shrinking response and colour change corresponding to the
      logical "OR" and "AND" gate. The visualization of the logic output signals is
      realized. 

PMID- 25874599
TI  - Macrophage and epithelial cell H-ferritin expression regulates renal
      inflammation.
AB  - Inflammation culminating in fibrosis contributes to progressive kidney disease.
      Cross-talk between the tubular epithelium and interstitial cells regulates
      inflammation by a coordinated release of cytokines and chemokines. Here we
      studied the role of heme oxygenase-1 (HO-1) and the heavy subunit of ferritin
      (FtH) in macrophage polarization and renal inflammation. Deficiency in HO-1 was
      associated with increased FtH expression, accumulation of macrophages with a
      dysregulated polarization profile, and increased fibrosis following unilateral
      ureteral obstruction in mice: a model of renal inflammation and fibrosis.
      Macrophage polarization in vitro was predominantly dependent on FtH expression in
      isolated bone marrow-derived mouse monocytes. Using transgenic mice with
      conditional deletion of FtH in the proximal tubules (FtH(PT-/-)) or myeloid cells
      (FtH(LysM-/-)), we found that myeloid FtH deficiency did not affect polarization
      or accumulation of macrophages in the injured kidney compared with wild-type
      (FtH(+/+)) controls. However, tubular FtH deletion led to a marked increase in
      proinflammatory macrophages. Furthermore, injured kidneys from FtH(PT-/-) mice
      expressed significantly higher levels of inflammatory chemokines and fibrosis
      compared with kidneys from FtH(+/+) and FtH(LysM-/-) mice. Thus, there are
      differential effects of FtH in macrophages and epithelial cells, which underscore
      the critical role of FtH in tubular-macrophage cross-talk during kidney injury. 

PMID- 25874603
TI  - Mass spectrometry-based methods for identifying oxidized proteins in disease:
      advances and challenges.
AB  - Many inflammatory diseases have an oxidative aetiology, which leads to oxidative
      damage to biomolecules, including proteins. It is now increasingly recognized
      that oxidative post-translational modifications (oxPTMs) of proteins affect cell
      signalling and behaviour, and can contribute to pathology. Moreover, oxidized
      proteins have potential as biomarkers for inflammatory diseases. Although many
      assays for generic protein oxidation and breakdown products of protein oxidation
      are available, only advanced tandem mass spectrometry approaches have the power
      to localize specific oxPTMs in identified proteins. While much work has been
      carried out using untargeted or discovery mass spectrometry approaches,
      identification of oxPTMs in disease has benefitted from the development of
      sophisticated targeted or semi-targeted scanning routines, combined with chemical
      labeling and enrichment approaches. Nevertheless, many potential pitfalls exist
      which can result in incorrect identifications. This review explains the
      limitations, advantages and challenges of all of these approaches to detecting
      oxidatively modified proteins, and provides an update on recent literature in
      which they have been used to detect and quantify protein oxidation in disease. 

PMID- 25874606
TI  - 3D-QSAR study of tetrahydro-3H-imidazo[4,5-c]pyridine derivatives as VEGFR-2
      kinase inhibitors using various charge schemes.
AB  - Vascular endothelial growth factor-2 receptor (VEGFR-2) kinase is a promising
      target for the development of novel anticancer drugs. Three-dimensional
      quantitative structure-activity relationship (3D-QSAR) study was performed on a
      series of tetrahydro-3H-imidazo[4,5-c]pyridine derivatives to understand the
      structural basis for VEGFR-2 inhibitory activity. Several 3D-QSAR models were
      developed using various partial atomic charge schemes. Comparative molecular
      field analysis (CoMFA) and Comparative molecular similarity indices analysis
      (CoMSIA) methods were employed to derive these models. The CoMFA models performed
      better than the CoMSIA models. The reliable CoMFA model was obtained with the
      Gasteiger-Marsili charge scheme. The model produced statistically significant
      results with a cross-validated correlation coefficient (q(2)) of 0.635 and a
      coefficient of determination (r(2)) of 0.930. The model showed reasonable
      predictive power with predictive correlation coefficient ([Formula: see text]) of
      0.582. Robustness of the model was further checked by leave-five-out cross
      validation, bootstrapping and progressive scrambling analysis. The model was
      found to be statistically robust and expected to assist in the design of novel
      compounds with enhanced VEGFR-2 inhibitory activity. 

PMID- 25874604
TI  - Regulation of AU-Rich Element RNA Binding Proteins by Phosphorylation and the
      Prolyl Isomerase Pin1.
AB  - The accumulation of 3' untranslated region (3'-UTR), AU-rich element (ARE)
      containing mRNAs, are predominantly controlled at the post-transcriptional level.
      Regulation appears to rely on a variable and dynamic interaction between mRNA
      target and ARE-specific binding proteins (AUBPs). The AUBP-ARE mRNA recognition
      is directed by multiple intracellular signals that are predominantly targeted at
      the AUBPs. These include (but are unlikely limited to) methylation, acetylation,
      phosphorylation, ubiquitination and isomerization. These regulatory events
      ultimately affect ARE mRNA location, abundance, translation and stability. In
      this review, we describe recent advances in our understanding of phosphorylation
      and its impact on conformation of the AUBPs, interaction with ARE mRNAs and
      highlight the role of Pin1 mediated prolyl cis-trans isomerization in these
      biological process. 

PMID- 25874607
TI  - Ultrasound-mediated oxygen delivery to lower extremity wounds.
AB  - Critical limb ischemia (CLI), an end result of peripheral ar- terial disease,
      remains a major clinical challenge. Wound healing in patients with CLI can be
      difficult due to diminished tissue oxygen- ation, often leading to recalcitrant
      ulcers and frequent limb loss. Nu- merous therapies, including hyperbaric oxygen
      therapy (HBOT), have been used to correct this regional ischemia, although often
      with mixed results. This case series investigates the effects of oxygen therapy
      de- livery augmented by low-frequency ultrasound, a device that combines surface
      acoustic waveform (SAW) low-frequency ultrasound with hyper- oxygenated saline to
      deliver oxygen to wounds. Participants included 7 patients (7 men, median age 63
      years, all with hypertension) with CLI and full-thickness wounds. Baseline
      therapy PaO2 measurements were taken before therapy, after provision of hyper
      oxygenated saline, and after sonification. The device was found to successfully
      oxygenate the wound beds; PaO2 levels increased by a median of 59.7%, a maximum
      of 116%, and a median absolute difference peaking at 10.8 mmHg PaO2 (P = 0.018).
      In conclusion, the treatment increases wound oxy- gen levels and may be an option
      in CLI therapy. 

PMID- 25874608
TI  - Cost effectiveness of an air-inflated static overlay for pressure ulcer
      prevention: a randomized, controlled trial.
AB  - Numerous pressure-relieving surfaces of varying costs are available for the
      prevention of pressure ulcers. There is insufficient evidence to draw conclusions
      regarding the efficacy or merits of using more expensive technologies. The
      purpose of this unblinded, randomized, prospective study was to compare the
      clinical and the cost effectiveness of an inflated overlay with rented, pressure
      relieving surfaces for the prevention of pressure ulcers. METHODS: Patients in a
      257-bed acute care facility were included if they had a Braden score of <= 14,
      had no skin lesion(s), were >= 18 years, weighed < 300 lb, and submitted signed
      consent. One hundred, ten patients (110) were randomized into a control group
      using either a microfluid static overlay (MSO) or a low-air-loss dynamic mattress
      (LALDM) with pulsation (n = 55) or into an experimental group using an inflated
      static overlay (ISO) (n = 55). Both groups had identical positioning protocols.
      No statistically significant differences were noted between the 2 groups with
      regard to age, gender, weight, or Braden scale score. Head-to-toe assessments
      were performed 3 times a week for a maximum of 14 days to deter- mine presence of
      pressure ulcers and comfort; Fisher's exact and chi- squared tests were used to
      assess categorical data, and unpaired t-test and Mann-Whitney statistic tests
      were used to compare continuous variables. Comparative cost of support surface
      use was determined at the end of the study. RESULTS: In the control group, 50
      patients used an MSO and 5 patients used an LALDM; in the experimental group, 55
      patients used an ISO. No significant difference in pressure ulcer incidence was
      found between the control (n = 6) and experimental groups (n = 2) (11% versus 4%,
      respectively; P = 0.2706), and there was no significant difference in comfort
      (90% versus 85%; P = 0.7129). However, a significant difference was noted in
      total cost ($13,606 CAD versus $3,364 CAD, P <= 0.001); the ISO was less
      expensive. CONCLUSION: The use of an ISO offers a cost-effective option for the
      prevention of pressure ulcers in a moderate to very high-risk population.    .

PMID- 25874609
TI  - Using Physical Modalities in the Treatment of Venous Leg Ulcers: A 14-year
      Comparative Clinical Study.
AB  - Venous ulcers are prevalent, challenging wounds; their incidence is rising with
      the increasing age of the general population. Physical mo- dalities often are
      used to help heal these chronic wounds. A prospective study was conducted to
      investigate the application of high-voltage stimu- lation (HVS), ultrasound
      therapy (US), low-level laser therapy (LLLT, 810 nm, 65 mW, 4 J/cm2), and
      compression therapy (CT), with and without surgical intervention; along with
      standard of care comprising drug therapy (micronized flavonoid fraction in two
      500-mg tablets once daily) and wet dressings of 0.9% sodium chloride on venous
      leg ulcer healing. METHODS: The 305-patient study was conducted between 1994 and
      2008 among persons with venous ulcers in 3 facilities in Poland. After surgery
      involving crossectomy, partial [short] stripping of the greater or short
      saphenous vein, local phlebectomy, and ligation of insufficient perforators, 4
      groups of patients were treated with the standard of care drug/dressing therapy
      and HVS, US, LLLT, or CT, and 1 group received the drug/dressing ther- apy only.
      Four non-surgical groups received HVS, US, LLLT, or CT and drug/dressing therapy,
      and 1 group received drug/dressing therapy only. Changes in wound area and volume
      were compared among all the groups receiving the various treatments using the
      Gilman index. In all groups therapy lasted 7 weeks. The computed planimetry
      method for observation of healing process was used. RESULTS: The Gilman index
      values at 4 weeks were significantly higher in the compression plus surgery
      compared with other groups (P = 0.01). After therapy for patients from the CT +
      surgery group, the Gilman index was 1.18 cm (P <= 0.001 compared with other
      groups). The percentage total surface area regression analysis confirmed that
      compression plus surgery is the most efficient in venous leg ulcer therapy
      (61.89% reduction after 4 weeks of therapy and 78.19% at the end of study)
      compared to the other groups (P <= 0.001). The HVS and US appeared useful only in
      conservatively treated patients (P < 0.05). The LLLT did not accelerate reduction
      of the ulceration surface. CONCLUSION: Venous surgery plus compression therapy is
      the most effi- cient treatment for venous leg ulcers. Compression therapy should
      be provided to both surgically and conservatively non-surgically treated pa-
      tients. High-voltage stimulation and ultrasound therapy are useful meth- ods in
      conservative treatment of venous leg ulcers. For surgically treated patients,
      these physical modalities are not effective. Low-level laser ther- apy is not an
      efficient method for treating venous leg ulcers.  .

PMID- 25874605
TI  - The Interplay between Alpha-Synuclein Clearance and Spreading.
AB  - Parkinson's Disease (PD) is a complex neurodegenerative disorder classically
      characterized by movement impairment. Pathologically, the most striking features
      of PD are the loss of dopaminergic neurons and the presence of intraneuronal
      protein inclusions primarily composed of alpha-synuclein (alpha-syn) that are
      known as Lewy bodies and Lewy neurites in surviving neurons. Though the
      mechanisms underlying the progression of PD pathology are unclear, accumulating
      evidence suggests a prion-like spreading of alpha-syn pathology. The
      intracellular homeostasis of alpha-syn requires the proper degradation of the
      protein by three mechanisms: chaperone-mediated autophagy, macroautophagy and
      ubiquitin-proteasome. Impairment of these pathways might drive the system towards
      an alternative clearance mechanism that could involve its release from the cell.
      This increased release to the extracellular space could be the basis for alpha
      syn propagation to different brain areas and, ultimately, for the spreading of
      pathology and disease progression. Here, we review the interplay between alpha
      syn degradation pathways and its intercellular spreading. The understanding of
      this interplay is indispensable for obtaining a better knowledge of the molecular
      basis of PD and, consequently, for the design of novel avenues for therapeutic
      intervention. 

PMID- 25874610
TI  - Clinical Experience With the Use of Gauze-based Negative Pressure Wound Therapy.
AB  - Purpose. In this preliminary study, gauze-based negative pressure wound therapy
      (NPWT) was used to accelerate granulation tissue forma- tion and promote closure
      in a number of wound types. The authors aimed to evaluate the efficacy of gauze
      based NPWT using the Chariker-Jeter technique for wounds requiring delayed
      closure. METHODS: A retrospective review was conducted of 50 patients with wounds
      not suitable for imme- diate primary closure. After initial irrigation,
      debridement, and antibiotic therapy, Chariker-Jeter technique NPWT was used and
      dressings were changed at 24- to 48-hour intervals before secondary closure or
      primary closure. In addition, a 4-point category scoring system (severe,
      moderate, mild, and none) was used to evaluate pain. Semi-quantitative data also
      were obtained. RESULTS: Wound size decreased considerably, granulation tissue
      formation was accelerated, and exudate was reduced and removed by the end of the
      treatment. The patients were followed for 12 months. Pre- and post-treatment
      averages of the wound surface areas were 90.21 +/- 74.97 cm2 and 35.71 +/- 53.63
      cm2, respectively (P < 0.001). Average duration of treatment was 12.98 +/- 3.18
      days and average wound size reduction following the treatment was 64.61% +/-
      30.42%. Granulation tissue was clinically observed in all wounds by day 5. Six
      cases healed without any operation; the others required various reconstructive
      methods to cover the wounds. After surgical intervention, only 3 patients treated
      with gauze-based NPWT had a recurrence. No infections were observed during the
      follow-up period. According to the pain form, only 2 patients had severe pain.
      CONCLUSION: The gauze-based NPWT was found to be a safe and cost-effective method
      in temporary soft-tissue management of chronic nonhealing wounds suitable delayed
      closure.    .

PMID- 25874611
TI  - Sodium salicylate reduced insulin resistance in the retina of a type 2 diabetic
      rat model.
AB  - Sodium salicylate has been reported to reduce markers of diabetic retinopathy in
      a type 1 rat model. Because rates of type 2 diabetes are on the rise, we wanted
      to determine whether salicylate could improve insulin resistance in a type 2 rat
      model, as well as improve retinal function. We treated lean and obese BBZDR/Wor
      type 2 diabetic rats with salicylate in their chow for 2 months. Prior to
      salicylate treatment, rats underwent an electroretinogram to measure retinal
      function. After 2 months of treatment, rats underwent an additional
      electroretinogram prior to sacrifice. In addition to the animal model, we also
      treated retinal endothelial cells (REC) and rat Muller cells with salicylate and
      performed the same analyses as done for the rat retinal lysates. To investigate
      the role of salicylate in insulin signaling, we measured TNFalpha and caspase 3
      levels by ELISA, as well as performed Western blotting for insulin receptor
      substrate 1, insulin receptor, SOCS3, and pro- and anti-apoptotic markers. Data
      demonstrated that salicylate significantly improved retinal function, as well as
      reduced TNFalpha and SOCS3-induced insulin resistance in all samples. Overall,
      results suggest that salicylate is effective in reducing insulin resistance in
      the retina of type 2 diabetic rat models. 

PMID- 25874612
TI  - MALDI-TOF mass spectrometry for the detection and differentiation of Entamoeba
      histolytica and Entamoeba dispar.
AB  - Detection of Entamoeba histolytica and its differentiation from Entamoeba dispar
      is an important goal of the clinical parasitology laboratory. The aim of this
      study was the identification and differentiation of E. histolytica and E. dispar
      by MALDI-TOF MS, in order to evaluate the application of this technique in
      routine diagnostic practice. MALDI-TOF MS was applied to 3 amebic reference
      strains and to 14 strains isolated from feces that had been differentiated by
      molecular methods in our laboratory. Protein extracts from cultures of these
      strains (axenic cultures for the 3 reference strains and monoxenic cultures for
      the 14 field isolates) were analyzed by MALDI-TOF MS and the spectra obtained
      were analyzed by statistical software. Five peaks discriminating between E.
      histolytica and E. dispar reference strains were found by protein profile
      analysis: 2 peaks (8,246 and 8,303 Da) specific for E. histolytica and 3 (4,714;
      5,541; 8,207 Da) for E. dispar. All clinical isolates except one showed the
      discriminating peaks expected for the appropriate species. For 2 fecal samples
      from which 2 strains (1 E. histolytica and 1 E. dispar) out of the 14 included in
      this study were isolated, the same discriminating peaks found in the
      corresponding isolated amebic strains were detected after only 12h (E.
      histolytica) and 24h (E. dispar) of incubation of the fecal samples in Robinson's
      medium without serum. Our study shows that MALDI-TOF MS can be used to
      discriminate between E. histolytica and E. dispar using in vitro xenic cultures
      and it also could have potential for the detection of these species in clinical
      samples. 

PMID- 25874613
TI  - Exercise programs for people with dementia.
AB  - BACKGROUND: This is an update of our previous 2013 review. Several recent trials
      and systematic reviews of the impact of exercise on people with dementia are
      reporting promising findings. OBJECTIVES: Primary objectiveDo exercise programs
      for older people with dementia improve their cognition, activities of daily
      living (ADLs), neuropsychiatric symptoms, depression, and mortality? Secondary
      objectivesDo 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, on 13
      August 2012, and again on 3 October 2013. 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,
      neuropsychiatric symptoms, 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. We analysed data
      for summary effects. 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: Seventeen
      trials with 1067 participants met the inclusion criteria. However, the required
      data from three included 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 revealed that there was no clear evidence of benefit from
      exercise on cognitive functioning. The estimated standardized mean difference
      between exercise and control groups was 0.43 (95% CI -0.05 to 0.92, P value 0.08;
      9 studies, 409 participants). There was very substantial heterogeneity in this
      analysis (I2 value 80%), most of which we were unable to explain, and we rated
      the quality of this evidence as very low. We found a benefit of exercise programs
      on the ability of people with dementia to perform ADLs in six trials with 289
      participants. The estimated standardized mean difference between exercise and
      control groups was 0.68 (95% CI 0.08 to 1.27, P value 0.02). However, again we
      observed considerable unexplained heterogeneity (I2 value 77%) in this meta
      analysis, and we rated the quality of this evidence as very low. This means that
      there is a need for caution in interpreting these findings.In further analyses,
      in one trial 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. The mean difference
      between exercise and control groups was -15.30 (95% CI -24.73 to -5.87; 1 trial,
      40 participants; P value 0.001). There was no apparent risk of bias in this
      study. In addition, there was no clear evidence of benefit from exercise on
      neuropsychiatric symptoms (MD -0.60, 95% CI -4.22 to 3.02; 1 trial, 110
      participants; P value .0.75), or depression (SMD 0.14, 95% CI -0.07 to 0.36; 5
      trials, 341 participants; P value 0.16). 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 may improve the ability to perform ADLs in people with dementia,
      although some caution is advised in interpreting these findings. The review
      revealed no evidence of benefit from exercise on cognition, neuropsychiatric
      symptoms, or depression. There was little or no evidence regarding the remaining
      outcomes of interest (i.e., mortality, caregiver burden, caregiver quality of
      life, caregiver mortality, and use of healthcare services).

PMID- 25874614
TI  - Thyroid hormone and estrogen regulate exercise-induced growth hormone release.
AB  - Growth hormone (GH) regulates whole body metabolism, and physical exercise is the
      most potent stimulus to induce its secretion in humans. The mechanisms underlying
      GH secretion after exercise remain to be defined. The aim of this study was to
      elucidate the role of estrogen and pituitary type 1 deiodinase (D1) activation on
      exercise-induced GH secretion. Ten days after bilateral ovariectomy, animals were
      submitted to 20 min of treadmill exercise at 75% of maximum aerobic capacity and
      tissues were harvested immediately or 30 min after exercise. Non-exercised
      animals were used as controls. A significant increase in D1 activity occurred
      immediately after exercise (~60%) in sham-operated animals and GH was higher (~6
      fold) 30 min after exercise. Estrogen deficient rats exhibited basal levels of GH
      and D1 activity comparable to those found in control rats. However, after
      exercise both D1 activity and serum GH levels were blunted compared to sedentary
      rats. To understand the potential cause-effect of D1 activation in exercise
      induced GH release, we pharmacologically blocked D1 activity by propylthiouracil
      (PTU) injection into intact rats and submitted them to the acute exercise
      session. D1 inhibition blocked exercise-induced GH secretion, although basal
      levels were unaltered. In conclusion, estrogen deficiency impairs the induction
      of thyroid hormone activating enzyme D1 in the pituitary, and GH release by acute
      exercise. Also, acute D1 activation is essential for exercise-induced GH
      response. 

PMID- 25874615
TI  - Tang-Nai-Kang alleviates pre-diabetes and metabolic disorders and induces a gene
      expression switch toward fatty acid oxidation in SHR.Cg-Leprcp/NDmcr rats.
AB  - Increased energy intake and reduced physical activity can lead to obesity,
      diabetes and metabolic syndrome. Transcriptional modulation of metabolic networks
      has become a focus of current drug discovery research into the prevention and
      treatment of metabolic disorders associated with energy surplus and obesity. Tang
      Nai-Kang (TNK), a mixture of five herbal plant extracts, has been shown to
      improve abnormal glucose metabolism in patients with pre-diabetes. Here, we
      report the metabolic phenotype of SHR.Cg-Leprcp/NDmcr (SHR/cp) rats treated with
      TNK. Pre-diabetic SHR/cp rats were randomly divided into control, TNK low-dose
      (1.67 g/kg) and TNK high-dose (3.24 g/kg) groups. After high-dose treatment for 2
      weeks, the serum triglycerides and free fatty acids in SHR/cp rats were markedly
      reduced compared to controls. After 3 weeks of administration, the high dose of
      TNK significantly reduced the body weight and fat mass of SHR/cp rats without
      affecting food consumption. Serum fasting glucose and insulin levels in the TNK
      treated groups decreased after 6 weeks of treatment. Furthermore, TNK-treated
      rats exhibited obvious improvements in glucose intolerance and insulin
      resistance. The improved glucose metabolism may be caused by the substantial
      reduction in serum lipids and body weight observed in SHR/cp rats starting at 3
      weeks of TNK treatment. The mRNA expression of NAD+-dependent deacetylase sirtuin
      1 (SIRT1) and genes related to fatty acid oxidation was markedly up-regulated in
      the muscle, liver and adipose tissue after TNK treatment. Furthermore, TNK
      promoted the deacetylation of two well-established SIRT1 targets, PPARgamma
      coactivator 1alpha (PGC1alpha) and forkhead transcription factor 1 (FOXO1), and
      induced the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA
      carboxylase (ACC) in different tissues. These observations suggested that TNK may
      be an alternative treatment for pre-diabetes and metabolic syndrome by inducing a
      gene expression switch toward fat oxidation through the activation of SIRT1 and
      AMPK signaling. 

PMID- 25874616
TI  - Targeting vascular endothelial growth factor receptor 2 and protein kinase D1
      related pathways by a multiple kinase inhibitor in angiogenesis and inflammation
      related processes in vitro.
AB  - Emerging evidence suggests that the vascular endothelial growth factor receptor 2
      (VEGFR2) and protein kinase D1 (PKD1) signaling axis plays a critical role in
      normal and pathological angiogenesis and inflammation related processes. Despite
      all efforts, the currently available therapeutic interventions are limited. Prior
      studies have also proved that a multiple target inhibitor can be more efficient
      compared to a single target one. Therefore, development of novel inflammatory
      pathway-specific inhibitors would be of great value. To test this possibility, we
      screened our molecular library using recombinant kinase assays and identified the
      previously described compound VCC251801 with strong inhibitory effect on both
      VEGFR2 and PKD1. We further analyzed the effect of VCC251801 in the endothelium
      derived EA.hy926 cell line and in different inflammatory cell types. In EA.hy926
      cells, VCC251801 potently inhibited the intracellular activation and signaling of
      VEGFR2 and PKD1 which inhibition eventually resulted in diminished cell
      proliferation. In this model, our compound was also an efficient inhibitor of in
      vitro angiogenesis by interfering with endothelial cell migration and tube
      formation processes. Our results from functional assays in inflammatory cellular
      models such as neutrophils and mast cells suggested an anti-inflammatory effect
      of VCC251801. The neutrophil study showed that VCC251801 specifically blocked the
      immobilized immune-complex and the adhesion dependent TNF-alpha -fibrinogen
      stimulated neutrophil activation. Furthermore, similar results were found in mast
      cell degranulation assay where VCC251801 caused significant reduction of mast
      cell response. In summary, we described a novel function of a multiple kinase
      inhibitor which strongly inhibits the VEGFR2-PKD1 signaling and might be a novel
      inhibitor of pathological inflammatory pathways.

PMID- 25874617
TI  - Where the lake meets the sea: strong reproductive isolation is associated with
      adaptive divergence between lake resident and anadromous three-spined
      sticklebacks.
AB  - Contact zones between divergent forms of the same species are often characterised
      by high levels of phenotypic diversity over small geographic distances. What
      processes are involved in generating such high phenotypic diversity? One
      possibility is that introgression and recombination between divergent forms in
      contact zones results in greater phenotypic and genetic polymorphism.
      Alternatively, strong reproductive isolation between forms may maintain distinct
      phenotypes, preventing homogenisation by gene flow. Contact zones between
      divergent freshwater-resident and anadromous stickleback (Gasterosteus aculeatus
      L.) forms are numerous and common throughout the species distribution, offering
      an opportunity to examine these contrasting hypotheses in greater detail. This
      study reports on an interesting new contact zone located in a tidally influenced
      lake catchment in western Ireland, characterised by high polymorphism for lateral
      plate phenotypes. Using neutral and QTL-linked microsatellite markers, we tested
      whether the high diversity observed in this contact zone arose as a result of
      introgression or reproductive isolation between divergent forms: we found strong
      support for the latter hypothesis. Three phenotypic and genetic clusters were
      identified, consistent with two divergent resident forms and a distinct
      anadromous completely plated population that migrates in and out of the system.
      Given the strong neutral differentiation detected between all three morphotypes
      (mean FST = 0.12), we hypothesised that divergent selection between forms
      maintains reproductive isolation. We found a correlation between neutral genetic
      and adaptive genetic differentiation that support this. While strong associations
      between QTL linked markers and phenotypes were also observed in this wild
      population, our results support the suggestion that such associations may be more
      complex in some Atlantic populations compared to those in the Pacific. These
      findings provide an important foundation for future work investigating the
      dynamics of gene flow and adaptive divergence in this newly discovered
      stickleback contact zone.

PMID- 25874618
TI  - The role of local knowledge and traditional extraction practices in the
      management of giant earthworms in Brazil.
AB  - The giant earthworm, Rhinodrilus alatus (Righi 1971), has been captured in the
      southeastern Brazilian Cerrado biome for approximately 80 years and used as bait
      for amateur fishing throughout Brazil. Local knowledge and traditional extraction
      practices are crucial for the establishment of management strategies for the
      species because, although its extraction involves conflicts and social and
      environmental impacts, the species is one of the major sources of income for
      approximately 3,000 people, especially for members of an Afro-descendant
      community that has approximately 2,000 inhabitants. Participatory tools, such as
      seasonal calendar, transect walks and participatory maps, were individually or
      collectively used with extractors and traders (former extractors), and 129 semi
      structured and unstructured interviews were conducted with the same individuals
      between 2005 and 2012. The capture of Rhinodrilus alatus was observed in
      different seasons and areas of occurrence of the species in 17 municipalities,
      where this giant earthworm is the only species extracted for trade. All
      information obtained was verified by community members in 17 meetings. The
      extractors have an extensive knowledge of the life history, behavior,
      distribution, and possible impacts of climate change on the species. Different
      capture techniques, which have different impacts, are used during the dry and
      rainy seasons and are passed by the extractors through the generations. Local
      knowledge contributed to the establishment of agreements for the use of capture
      techniques that have less impact, to the expansion of scientific knowledge and
      the reassessment of the conservation status of Rhinodrilus alatus. The present
      study may serve as an example for management projects for other giant earthworm
      species in other regions of Brazil and in other countries. 

PMID- 25874619
TI  - Beneficial effects of hydrogen-rich saline on early burn-wound progression in
      rats.
AB  - INTRODUCTION: Deep burn wounds undergo a dynamic process known as wound
      progression that results in a deepening and extension of the initial burn area.
      The zone of stasis is more likely to develop more severe during wound progression
      in the presence of hypoperfusion. Hydrogen has been reported to alleviate injury
      triggered by ischaemia/reperfusion and burns in various organs by selectively
      quenching oxygen free radicals. The aim of this study was to investigate the
      possible protective effects of hydrogen against early burn-wound progression.
      METHODS: Deep-burn models were established through contact with a boiled,
      rectangular, brass comb for 20 s. Fifty-six Sprague-Dawley rats were randomly
      divided into sham, burn plus saline, and burn plus hydrogen-rich saline (HS)
      groups with sacrifice and analysis at various time windows (6 h, 24 h, 48 h) post
      burn. Indexes of oxidative stress, apoptosis and autophagy were measured in each
      group. The zone of stasis was evaluated using immunofluorescence staining, ELISA,
      and Western blot to explore the underlying effects and mechanisms post burn.
      RESULTS: The burn-induced increase in malondialdehyde was markedly reduced with
      HS, while the activities of endogenous antioxidant enzymes were significantly
      increased. Moreover, HS treatment attenuated increases in apoptosis and autophagy
      postburn in wounds, according to the TUNEL staining results and the expression
      analysis of Bax, Bcl-2, caspase-3, Beclin-1 and Atg-5 proteins. Additionally, HS
      lowered the level of myeloperoxidase and expression of TNF-alpha, IL-1beta, and
      IL-6 in the zone of stasis while augmenting IL-10. The elevated levels of Akt
      phosphorylation and NF-kappaB p65 expression post burn were also downregulated by
      HS management. CONCLUSION: Hydrogen can attenuate early wound progression
      following deep burn injury. The beneficial effect of hydrogen was mediated by
      attenuating oxidative stress, which inhibited apoptosis and inflammation, and the
      Akt/NF-kappaB signalling pathway may be involved in regulating the release of
      inflammatory cytokines.

PMID- 25874620
TI  - Use of renin-angiotensin system inhibitors is associated with reduction of
      fracture risk in hemodialysis patients.
AB  - BACKGROUND: Patients with chronic kidney disease, especially those undergoing
      dialysis treatment and having secondary hyperparathyroidism, have a high risk of
      bone fracture. The renin-angiotensin system (RAS) is associated with osteoclastic
      bone resorption. We aimed to examine whether the use of RAS inhibitors reduces
      the incidence of fracture in hemodialysis patients. METHODS AND FINDINGS: This
      was a multicenter, 3-year, prospective, observational study. From 2008 to 2011,
      maintenance hemodialysis patients with secondary hyperparathyroidism (N = 3,276)
      treated with angiotensin converting enzyme inhibitor (ACEI)/angiotensin II
      receptor blocker (ARB) at baseline were followed for a mean of 2.7 years. The
      association between the use of ACEI/ARB and hospitalization rate owing to
      fracture was examined by using Cox regression models. Effect modifications by the
      severity of secondary hyperparathyroidism (intact parathyroid hormone [iPTH]
      level), sex, and systolic blood pressure were also examined. The incidence
      proportion of fracture-related hospitalization was 5.42% throughout the
      observation period. ACEI/ARB use was associated with a lower rate of fracture
      related hospitalization (adjusted hazard ratio, 0.65; 95% confidence interval
      [CI], 0.45-0.92). This association was not significantly affected by sex (P =
      0.56) or systolic blood pressure levels (P = 0.87). The hazard ratios adjusted by
      iPTH levels were qualitatively different, but not statistically significant (P =
      0.11): 0.77 (95% CI, 0.42-1.39), 0.38 (95% CI, 0.20-0.73), 0.59 (95% CI, 0.29
      1.21), and 1.29 (95% CI, 0.58-2.42) for the first, second, third and fourth
      quartiles of iPTH, respectively. CONCLUSIONS: Use of RAS inhibitors is associated
      with a lower rate of fracture-related hospitalization in hemodialysis patients
      with secondary hyperparathyroidism. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT00995163.

PMID- 25874621
TI  - A critical period for postnatal adaptive plasticity in a model of motor axon
      miswiring.
AB  - The correct wiring of neuronal circuits is of crucial importance for precise
      neuromuscular functionality. Therefore, guidance cues provide tight
      spatiotemporal control of axon growth and guidance. Mice lacking the guidance cue
      Semaphorin 3F (Sema3F) display very specific axon wiring deficits of motor
      neurons in the medial aspect of the lateral motor column (LMCm). While these
      deficits have been investigated extensively during embryonic development, it
      remained unclear how Sema3F mutant mice cope with these errors postnatally. We
      therefore investigated whether these animals provide a suitable model for the
      exploration of adaptive plasticity in a system of miswired neuronal circuitry. We
      show that the embryonically developed wiring deficits in Sema3F mutants persist
      until adulthood. As a consequence, these mutants display impairments in motor
      coordination that improve during normal postnatal development, but never reach
      wildtype levels. These improvements in motor coordination were boosted to
      wildtype levels by housing the animals in an enriched environment starting at
      birth. In contrast, a delayed start of enriched environment housing, at 4 weeks
      after birth, did not similarly affect motor performance of Sema3F mutants. These
      results, which are corroborated by neuroanatomical analyses, suggest a critical
      period for adaptive plasticity in neuromuscular circuitry. Interestingly, the
      formation of perineuronal nets, which are known to close the critical period for
      plastic changes in other systems, was not altered between the different housing
      groups. However, we found significant changes in the number of excitatory
      synapses on limb innervating motor neurons. Thus, we propose that during the
      early postnatal phase, when perineuronal nets have not yet been formed around
      spinal motor neurons, housing in enriched environment conditions induces adaptive
      plasticity in the motor system by the formation of additional synaptic contacts,
      in order to compensate for coordination deficits. 

PMID- 25874622
TI  - Optimising and communicating options for the control of invasive plant disease
      when there is epidemiological uncertainty.
AB  - Although local eradication is routinely attempted following introduction of
      disease into a new region, failure is commonplace. Epidemiological principles
      governing the design of successful control are not well-understood. We analyse
      factors underlying the effectiveness of reactive eradication of localised
      outbreaks of invading plant disease, using citrus canker in Florida as a case
      study, although our results are largely generic, and apply to other plant
      pathogens (as we show via our second case study, citrus greening). We demonstrate
      how to optimise control via removal of hosts surrounding detected infection (i.e.
      localised culling) using a spatially-explicit, stochastic epidemiological model.
      We show how to define optimal culling strategies that take account of
      stochasticity in disease spread, and how the effectiveness of disease control
      depends on epidemiological parameters determining pathogen infectivity, symptom
      emergence and spread, the initial level of infection, and the logistics and
      implementation of detection and control. We also consider how optimal culling
      strategies are conditioned on the levels of risk acceptance/aversion of decision
      makers, and show how to extend the analyses to account for potential larger-scale
      impacts of a small-scale outbreak. Control of local outbreaks by culling can be
      very effective, particularly when started quickly, but the optimum strategy and
      its performance are strongly dependent on epidemiological parameters
      (particularly those controlling dispersal and the extent of any cryptic
      infection, i.e. infectious hosts prior to symptoms), the logistics of detection
      and control, and the level of local and global risk that is deemed to be
      acceptable. A version of the model we developed to illustrate our methodology and
      results to an audience of stakeholders, including policy makers, regulators and
      growers, is available online as an interactive, user-friendly interface at
      http://www.webidemics.com/. This version of our model allows the complex
      epidemiological principles that underlie our results to be communicated to a non
      specialist audience. 

PMID- 25874624
TI  - Correction: Transcriptome analysis of Bombyx mori larval midgut during persistent
      and pathogenic cytoplasmic polyhedrosis virus infection.

PMID- 25874623
TI  - Acid gradient across plasma membrane can drive phosphate bond synthesis in cancer
      cells: acidic tumor milieu as a potential energy source.
AB  - Aggressive cancers exhibit an efficient conversion of high amounts of glucose to
      lactate accompanied by acid secretion, a phenomenon popularly known as the
      Warburg effect. The acidic microenvironment and the alkaline cytosol create a
      proton-gradient (acid gradient) across the plasma membrane that represents proton
      motive energy. Increasing experimental data from physiological relevant models
      suggest that acid gradient stimulates tumor proliferation, and can also support
      its energy needs. However, direct biochemical evidence linking extracellular acid
      gradient to generation of intracellular ATP are missing. In this work, we
      demonstrate that cancer cells can synthesize significant amounts of phosphate
      bonds from phosphate in response to acid gradient across plasma membrane. The
      noted phenomenon exists in absence of glycolysis and mitochondrial ATP synthesis,
      and is unique to cancer. Biochemical assays using viable cancer cells, and
      purified plasma membrane vesicles utilizing radioactive phosphate, confirmed
      phosphate-bond synthesis from free phosphate (Pi), and also localization of this
      activity to the plasma membrane. In addition to ATP, predominant formation of
      pyrophosphate (PPi) from Pi was also observed when plasma membrane vesicles from
      cancer cells were subjected to trans-membrane acid gradient. Cancer cytosols were
      found capable of converting PPi to ATP, and also stimulate ATP synthesis from Pi
      from the vesicles. Acid gradient created through glucose metabolism by cancer
      cells, as observed in tumors, also proved critical for phosphate-bond synthesis.
      In brief, these observations reveal a role of acidic tumor milieu as a potential
      energy source and may offer a novel therapeutic target. 

PMID- 25874625
TI  - Social capital and health-protective behavior intentions in an influenza
      pandemic.
AB  - Health-protective behaviors, such as receiving a vaccine, wearing a face mask,
      and washing hands frequently, can reduce the risk of contracting influenza.
      However, little is known about how social capital may influence health-protective
      behavior in the general population. This study examined whether each of the
      social capital dimensions (bonding, bridging, and linking) contributed to the
      intention to adopt any of the health-protective behaviors in an influenza
      pandemic. The data of this study were from the 2014 Taiwan Social Change Survey.
      A stratified, three-stage probability proportional-to-size sampling from across
      the nation, was conducted to select adults aged 20 years and older (N = 1,745).
      Bonding social capital was measured by the frequency of neighborly contact and
      support. Bridging social capital was measured based on association membership.
      Linking social capital was measured according to general government trust and
      trust in the government's capacity to counter an influenza pandemic. Binary
      logistic regressions were used to assess the multivariate associations between
      social capital and behavioral intention. The study results indicate that social
      capital may influence the response to influenza pandemic. Specifically, the
      intention to receive a vaccine and to wash hands more frequently were associated
      with the linking dimension and the bonding dimension of social capital, while the
      intention to wear a face mask was associated with all forms of social capital.
      The findings of this study suggest that government credibility and interpersonal
      networks may play a crucial role in health-protective behavior. This study
      provides new insights into how to improve the effectiveness of influenza
      prevention campaigns. 

PMID- 25874626
TI  - RNA-Seq analysis and gene discovery of Andrias davidianus using Illumina short
      read sequencing.
AB  - The Chinese giant salamander, Andrias davidianus, is an important species in the
      course of evolution; however, there is insufficient genomic data in public
      databases for understanding its immunologic mechanisms. High-throughput
      transcriptome sequencing is necessary to generate an enormous number of
      transcript sequences from A. davidianus for gene discovery. In this study, we
      generated more than 40 million reads from samples of spleen and skin tissue using
      the Illumina paired-end sequencing technology. De novo assembly yielded 87,297
      transcripts with a mean length of 734 base pairs (bp). Based on the sequence
      similarities, searching with known proteins, 38,916 genes were identified. Gene
      enrichment analysis determined that 981 transcripts were assigned to the immune
      system. Tissue-specific expression analysis indicated that 443 of transcripts
      were specifically expressed in the spleen and skin. Among these transcripts, 147
      transcripts were found to be involved in immune responses and inflammatory
      reactions, such as fucolectin, beta-defensins and lymphotoxin beta. Eight tissue
      specific genes were selected for validation using real time reverse transcription
      quantitative PCR (qRT-PCR). The results showed that these genes were
      significantly more expressed in spleen and skin than in other tissues, suggesting
      that these genes have vital roles in the immune response. This work provides a
      comprehensive genomic sequence resource for A. davidianus and lays the foundation
      for future research on the immunologic and disease resistance mechanisms of A.
      davidianus and other amphibians. 

PMID- 25874627
TI  - MT-4 suppresses resistant ovarian cancer growth through targeting tubulin and
      HSP27.
AB  - OBJECTIVE: In this study, the anticancer mechanisms of MT-4 were examined in
      A2780 and multidrug-resistant NCI-ADR/res human ovarian cancer cell lines.
      METHODS: To evaluate the activity of MT-4, we performed in vitro cell viability
      and cell cycle assays and in vivo xenograft assays. Immunoblotting analysis was
      carried out to evaluate the effect of MT-4 on ovarian cancer. Tubulin
      polymerization was determined using a tubulin binding assay. RESULTS: MT-4 (2
      Methoxy-5-[2-(3,4,5-trimethoxy-phenyl)-ethyl]-phenol), a derivative of
      moscatilin, can inhibit both sensitive A2780 and multidrug-resistant NCI-ADR/res
      cell growth and viability. MT-4 inhibited tubulin polymerization to induce G2/M
      arrest followed by caspase-mediated apoptosis. Further studies indicated that MT
      4 is not a substrate of P-glycoprotein (p-gp). MT-4 also caused G2/M cell cycle
      arrest, accompanied by the upregulation of cyclin B, p-Thr161 Cdc2/p34, polo-like
      kinase 1 (PLK1), Aurora kinase B, and phospho-Ser10-histone H3 protein levels. In
      addition, we found that p38 MAPK pathway activation was involved in MT-4-induced
      apoptosis. Most importantly, MT-4 also decreased heat shock protein 27 expression
      and reduced its interaction with caspase-3, which inured cancer cells to
      chemotherapy resistance. Treatment of cells with SB203580 or overexpression of
      dominant negative (DN)-p38 or wild-type HSP27 reduced PARP cleavage caused by MT
      4. MT-4 induced apoptosis through regulation of p38 and HSP27. Our xenograft
      models also show the in vivo efficacy of MT-4. MT-4 inhibited both A2780 and NCI
      ADR/res cell growth in vitro and in vivo. CONCLUSION: These findings indicate
      that MT-4 could be a potential lead compound for the treatment of multidrug
      resistant ovarian cancer.

PMID- 25874628
TI  - A systematic model specification procedure for an illness-death model without
      recovery.
AB  - Multi-state models are a flexible tool for analyzing complex time-to-event
      problems with multiple endpoints. Compared to the Cox regression model with a
      single endpoint or a summarizing composite endpoint, they can provide a more
      detailed insight into the disease process. Furthermore, prognosis can be improved
      by including information from intermediate events occurring during the course of
      the disease. Different model variants, options and additional assumptions provide
      many possibilities, but at the same time complicate the implementation of multi
      state techniques. So far, no guiding literature is available to specify a multi
      state model systematically. The objective of this work was to set up a general
      specification procedure for an illness-death model that optimizes the model fit
      and predictive accuracy by stepwise reduction of the model. As an application
      example, we reanalyzed data from an observational study of 434 ovarian cancer
      patients with progression as intermediate and death as absorbing state. The
      technique is described in general terms and can be applied to other illness-death
      models without recovery. The clock-reset approach was used, implicating that the
      time was reset to zero after progression. The non-homogeneous semi-Markov
      characteristic stated that the present time as well as the time between surgery
      and progression influenced survival after progression. Covariate effects on
      transitions were estimated and proportionality of transition baseline hazards was
      tested. The finally developed model optimized the accuracy of predictions for two
      simulated patients. This stepwise procedure yields parsimonious but targeted
      multi-state models with well interpretable coefficients and optimized predictive
      ability, even for smaller data sets. 

PMID- 25874629
TI  - Removal of transmissible spongiform encephalopathy prion from large volumes of
      cell culture media supplemented with fetal bovine serum by using hollow fiber
      anion-exchange membrane chromatography.
AB  - Cases of variant Creutzfeldt-Jakob disease in people who had consumed
      contaminated meat products from cattle with bovine spongiform encephalopathy
      emphasize the need for measures aimed at preventing the transmission of the
      pathogenic prion protein (PrPSc) from materials derived from cattle. Highly
      stringent scrutiny is required for fetal bovine serum (FBS), a growth-medium
      supplement used in the production of parenteral vaccines and therapeutic
      recombinant proteins and in the ex vivo expansion of stem cells for
      transplantation. One such approach is the implementation of manufacturing steps
      dedicated to removing PrPSc from materials containing FBS. We evaluated the use
      of the QyuSpeed D (QSD) adsorbent hollow-fiber anion-exchange chromatographic
      column (Asahi Kasei Medical, Tokyo, Japan) for the removal of PrPSc from cell
      culture media supplemented with FBS. We first established that QSD filtration had
      no adverse effect on the chemical composition of various types of culture media
      supplemented with 10% FBS or the growth and viability characteristics of human
      embryonic kidney (HEK293) cells, baby hamster kidney (BHK-21) cells, African
      green monkey kidney (Vero) cells, and Chinese hamster ovary (CHO-k1) cells
      propagated in the various culture-medium filtrates. We used a 0.6-mL QSD column
      for removing PrPSc from up to 1000 mL of Dulbecco's modified Eagle's medium
      containing 10% FBS previously spiked with the 263K strain of hamster-adapted
      scrapie. The Western blot analysis, validated alongside an infectivity assay,
      revealed that the level of PrPSc in the initial 200mL flow-through was reduced by
      2.5 to > 3 log10, compared with that of the starting material. These results
      indicate that QSD filtration removes PrPSc from cell culture media containing 10%
      FBS, and demonstrate the ease with which QSD filtration can be implemented in at
      industrial-scale to improve the safety of vaccines, therapeutic recombinant
      proteins, and ex vivo expanded stem cells produced using growth media
      supplemented with FBS. 

PMID- 25874630
TI  - Environmental DNA (eDNA) sampling improves occurrence and detection estimates of
      invasive burmese pythons.
AB  - Environmental DNA (eDNA) methods are used to detect DNA that is shed into the
      aquatic environment by cryptic or low density species. Applied in eDNA studies,
      occupancy models can be used to estimate occurrence and detection probabilities
      and thereby account for imperfect detection. However, occupancy terminology has
      been applied inconsistently in eDNA studies, and many have calculated occurrence
      probabilities while not considering the effects of imperfect detection. Low
      detection of invasive giant constrictors using visual surveys and traps has
      hampered the estimation of occupancy and detection estimates needed for
      population management in southern Florida, USA. Giant constrictor snakes pose a
      threat to native species and the ecological restoration of the Florida
      Everglades. To assist with detection, we developed species-specific eDNA assays
      using quantitative PCR (qPCR) for the Burmese python (Python molurus bivittatus),
      Northern African python (P. sebae), boa constrictor (Boa constrictor), and the
      green (Eunectes murinus) and yellow anaconda (E. notaeus). Burmese pythons,
      Northern African pythons, and boa constrictors are established and reproducing,
      while the green and yellow anaconda have the potential to become established. We
      validated the python and boa constrictor assays using laboratory trials and
      tested all species in 21 field locations distributed in eight southern Florida
      regions. Burmese python eDNA was detected in 37 of 63 field sampling events;
      however, the other species were not detected. Although eDNA was heterogeneously
      distributed in the environment, occupancy models were able to provide the first
      estimates of detection probabilities, which were greater than 91%. Burmese python
      eDNA was detected along the leading northern edge of the known population
      boundary. The development of informative detection tools and eDNA occupancy
      models can improve conservation efforts in southern Florida and support more
      extensive studies of invasive constrictors. Generic sampling design and
      terminology are proposed to standardize and clarify interpretations of eDNA-based
      occupancy models. 

PMID- 25874631
TI  - Higher thermal acclimation potential of respiration but not photosynthesis in two
      alpine Picea taxa in contrast to two lowland congeners.
AB  - The members of the genus Picea form a dominant component in many alpine and
      boreal forests which are the major sink for atmospheric CO2. However, little is
      known about the growth response and acclimation of CO2 exchange characteristics
      to high temperature stress in Picea taxa from different altitudes. Gas exchange
      parameters and growth characteristics were recorded from four year old seedlings
      of two alpine (Picea likiangensis vars. rubescens and linzhiensis) and two
      lowland (P. koraiensis and P. meyeri) taxa. Seedlings were grown at moderate (25
      degrees C/15 degrees C) and high (35 degrees C/25 degrees C) day/night
      temperatures, for four months. The approximated biomass increment (DeltaD2H) for
      all taxa decreased under high temperature stress, associated with decreased
      photosynthesis and increased respiration. However, the two alpine taxa exhibited
      lower photosynthetic acclimation and higher respiratory acclimation than either
      lowland taxon. Moreover, higher leaf dry mass per unit area (LMA) and leaf
      nitrogen content per unit area (Narea), and a smaller change in the nitrogen use
      efficiency of photosynthesis (PNUE) for lowland taxa indicated that these
      maintained higher homeostasis of photosynthesis than alpine taxa. The higher
      respiration rates produced more energy for repair and maintenance biomass,
      especially for higher photosynthetic activity for lowland taxa, which causes
      lower respiratory acclimation. Thus, the changes of DeltaD2H for alpine spruces
      were larger than that for lowland spruces. These results indicate that long term
      heat stress negatively impact on the growth of Picea seedlings, and alpine taxa
      are more affected than low altitude ones by high temperature stress. Hence the
      altitude ranges of Picea taxa should be taken into account when predicting
      changes to carbon fluxes in warmer conditions. 

PMID- 25874632
TI  - Optimization of antigen dose for a receptor-binding domain-based subunit vaccine
      against MERS coronavirus.
AB  - Middle East respiratory syndrome (MERS) is an emerging infectious disease caused
      by MERS coronavirus (MERS-CoV). The continuous increase of MERS cases has posed a
      serious threat to public health worldwide, calling for development of safe and
      effective MERS vaccines. We have previously shown that a recombinant protein
      containing residues 377-588 of MERS-CoV receptor-binding domain (RBD) fused with
      human Fc (S377-588-Fc) induced highly potent anti-MERS-CoV neutralizing
      antibodies in the presence of MF59 adjuvant. Here we optimized the doses of S377
      588-Fc using MF59 as an adjuvant in order to elicit strong immune responses with
      minimal amount of antigen. Our results showed that S377-588-Fc at 1 MUg was able
      to induce in the immunized mice potent humoral and cellular immune responses.
      Particularly, S377-588-Fc at 1 MUg elicited strong neutralizing antibody
      responses against both pseudotyped and live MERS-CoV similar to those induced at
      5 and 20 MUg, respectively. These results suggest that this RBD-based subunit
      MERS vaccine candidate at the dose as low as one MUg is sufficiently potent to
      induce strong humoral and cellular immune responses, including neutralizing
      antibodies, against MERS-CoV infection, thus providing guidance for determining
      the optimal dosage of RBD-based MERS vaccines in the future clinical trials and
      for applying the dose-sparing strategy in other subunit vaccine trials.

PMID- 25874633
TI  - Calpain inhibitor PD150606 attenuates glutamate induced spiral ganglion neuron
      apoptosis through apoptosis inducing factor pathway in vitro.
AB  - OBJECTIVE: This research aimed to investigate whether glutamate induced spiral
      ganglion neurons (SGNs) apoptosis through apoptosis inducing factor (AIF)
      pathway. And verify whether PD150606, a calpain inhibitor could prevent apoptosis
      by inhibiting cleaving and releasing AIF in mitochondrion. METHODS: SGNs of
      postnatal days 0-3 were harvested and cultured in dishes. 20 mM Glu, the caspase
      inhibitor Z-VAD-FMK and calpain inhibitor PD150606 were added into cultured
      dishes separately. We used optical microscope and immunofluoresence staining to
      observe cell morphology and AIF distribution, RT-PCR and Westernblot to analyse
      AIF and calpain expression in SGNs. TUNEL assay was used to test cell apoptosis.
      RESULTS: Cell morphology and nuclear translocation of AIF were altered in SGNs by
      20 mM Glu treated in vitro. The axon of SGN shortened, more apoptosis SGN were
      observed and the expression of AIF and calpain were up-regulated in Glu-treated
      group than the normal one (P<0.05). The same experiments were conducted in 20
      mM+PD150606 treated group and 20 mM+Z-VAD-FMK group. Obviously AIF were located
      from cytoplasm to the nuclear and the expressions of AIF and calpain were down
      regulated by PD150606 (P<0.05). Positive cells in TUNEL staining decreased after
      PD150606 treating. However, Z-VAD-FMK had no influence on AIF, calpain expression
      or cell apoptosis. CONCLUSION: The AIF-related apoptosis pathway is involved in
      the process of Glu-induced SGN injury. Furthermore, the inhibition of calpain can
      prevent AIF from releasing the nuclear or inducing SGN apoptosis.

PMID- 25874634
TI  - Role of environmental pollutants in liver physiology: special references to
      peoples living in the oil drilling sites of Assam.
AB  - The populations residing near polluted sites are more prone to various types of
      diseases. The important causes of air pollution are the suspended particulate
      matter, respirable suspended particulate matter, sulfur dioxide and nitrogen
      dioxide. As limited information is available enumerating the effect of these
      pollutants on liver physiology of the population living near the polluted sites;
      in the present study, we tried to investigate their effect on liver of the
      population residing near the oil drilling sites since birth. In this study, a
      randomly selected 105 subjects (46 subjects from oil drilling site and 61
      subjects from control site) aged above 30 years were taken under consideration.
      The particulate matter as well as the gaseous pollutants, sulfur dioxide and
      nitrogen dioxide, were analyzed through a respirable dust sampler. The level of
      alkaline phosphatase, alanine transaminase and aspartate transaminase enzymes in
      serum were measured by spectrophotometer. The generalized regression model
      studies suggests a higher concentration of respirable suspended particulate
      matter, suspended particulate matter and nitrogen dioxide lowers the alkaline
      phosphatase level (p<0.0001) by 3.5 times (95% CI 3.1-3.9), 1.5 times (95% CI 1.4
      1.6) and 12 times (95% CI 10.74-13.804), respectively in the exposed group. The
      higher concentration of respirable suspended particulate matter and nitrogen
      dioxide in air was associated with increase in alanine transaminase level
      (p<0.0001) by 0.8 times (95% CI 0.589-1.049) and by 2.8 times (95% CI 2.067
      3.681) respectively in the exposed group. The increase in nitrogen dioxide level
      was also associated with increase in aspartate transaminase level (p<0.0001) by
      2.5 times (95% CI 1.862-3.313) in the exposed group as compared to control group.
      Thus, the study reveals that long-term exposure to the environmental pollutants
      may lead to liver abnormality or injury of populations living in polluted sites.

PMID- 25874635
TI  - How do i fit through that gap? Navigation through apertures in adults with and
      without developmental coordination disorder.
AB  - During everyday life we move around busy environments and encounter a range of
      obstacles, such as a narrow aperture forcing us to rotate our shoulders in order
      to pass through. In typically developing individuals the decision to rotate the
      shoulders is body scaled and this movement adaptation is temporally and spatially
      tailored to the size of the aperture. This is done effortlessly although it
      actually involves many complex skills. For individuals with Developmental
      Coordination Disorder (DCD) moving in a busy environment and negotiating
      obstacles presents a real challenge which can negatively impact on safety and
      participation in motor activities in everyday life. However, we have a limited
      understanding of the nature of the difficulties encountered. Therefore, this
      current study considered how adults with DCD make action judgements and movement
      adaptations while navigating apertures. Fifteen adults with DCD and 15 typically
      developing (TD) controls passed through a series of aperture sizes which were
      scaled to body size (0.9-2.1 times shoulder width). Spatial and temporal
      characteristics of movement were collected over the approach phase and while
      crossing the aperture. The decision to rotate the shoulders was not scaled in the
      same way for the two groups, with the adults with DCD showing a greater
      propensity to turn for larger apertures compared to the TD adults when body size
      alone was accounted for. However, when accounting for degree of lateral trunk
      movement and variability on the approach, we no longer saw differences between
      the two groups. In terms of the movement adaptations, the adults with DCD
      approached an aperture differently when a shoulder rotation was required and then
      adapted their movement sooner compared to their typical peers. These results
      point towards an adaptive strategy in adults with DCD which allows them to
      account for their movement difficulties and avoid collision. 

PMID- 25874636
TI  - CMPF does not associate with impaired glucose metabolism in individuals with
      features of metabolic syndrome.
AB  - OBJECTIVE: 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) is a
      metabolite produced endogenously from dietary sources of furan fatty acids. The
      richest source of furan fatty acids in human diet is fish. CMPF was recently
      shown to be elevated in fasting plasma in individuals with gestational diabetes
      and type 2 diabetes, and mechanistically high level of CMPF was linked to beta
      cell dysfunction. Here we aimed to study the association between plasma CMPF
      level and glucose metabolism in persons with impaired glucose metabolism.
      METHODS: Plasma CMPF concentration was measured from plasma samples of the study
      participants in an earlier controlled dietary intervention. All of them had
      impaired glucose metabolism and two other characteristics of the metabolic
      syndrome. Altogether 106 men and women were randomized into three groups for 12
      weeks with different fish consumption (either three fatty fish meals per week,
      habitual fish consumption or maximum of one fish meal per week). Associations
      between concentration of CMPF and various glucose metabolism parameters at an
      oral glucose tolerance test at baseline and at the end of the study were studied.
      RESULTS: Fasting plasma CMPF concentration was significantly increased after a 12
      week consumption of fatty fish three times per week, but the concentration
      remained much lower compared to concentrations reported in diabetic patients.
      Increases of plasma CMPF concentrations mostly due to increased fish consumption
      were not associated with impaired glucose metabolism in this study. Instead,
      elevated plasma CMPF concentration was associated with decreased 2-hour insulin
      concentration in OGTT. CONCLUSIONS: Moderately elevated concentration of CMPF in
      plasma resulting from increased intake of fish is not harmful to glucose
      metabolism. Further studies are needed to fully explore the role of CMPF in the
      pathogenesis of impaired glucose metabolism. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT00573781.

PMID- 25874637
TI  - Effects of dual-task training on balance and executive functions in Parkinson's
      disease: A pilot study.
AB  - The aim of this study was to analyze the efficacy of cognitive-motor dual-task
      training compared with single-task training on balance and executive functions in
      individuals with Parkinson's disease. Fifteen subjects, aged between 39 and 75
      years old, were randomly assigned to the dual-task training group (n = 8) and
      single-task training group (n = 7). The training was run twice a week for 6
      weeks. The single-task group received balance training and the dual-task group
      performed cognitive tasks simultaneously with the balance training. There were no
      significant differences between the two groups at baseline. After the
      intervention, the results for mediolateral sway with eyes closed were
      significantly better for the dual-task group and anteroposterior sway with eyes
      closed was significantly better for the single-task group. The results suggest
      superior outcomes for the dual-task training compared to the single-task training
      for static postural control, except in anteroposterior sway with eyes closed.

PMID- 25874638
TI  - The effect of tonic contraction of the finger muscle on the motor cortical
      representation of the contracting adjacent muscle.
AB  - This study examined the effect of tonic contraction of the finger muscle on the
      motor cortical representation of the contracting adjacent muscle. A
      representation map of the motor evoked potential (MEP) in the first dorsal
      interosseous (FDI) and abductor digiti minimi (ADM) muscles was obtained with the
      subject at rest or during tonic contraction of the ADM muscle while the FDI
      muscle was tonically contracted. The center of gravity (COG) of the MEP map in
      the FDI muscle shifted medially during contraction of the ADM muscle. Motor
      cortical excitability in the motor cortical representation of the FDI muscle that
      did not overlap with the motor cortical representation of the ADM muscle was
      suppressed, but motor cortical excitability in the motor cortical representation
      of the FDI muscle overlapping with the motor cortical representation of the ADM
      muscle was not suppressed during contraction of the ADM muscle. The motor
      cortical representation of the FDI muscle not overlapping with the motor cortical
      representation of the ADM muscle was located lateral to that of the FDI muscle
      that did overlap with the motor cortical representation of the ADM muscle. Medial
      shift of the COG of the motor cortical representation of the contracting finger
      muscle induced by tonic contraction of the adjacent finger muscle must be due to
      suppression of motor cortical excitability in the lateral part of the
      representation, which is not shared by the adjacent representation. 

PMID- 25874639
TI  - Clinical application of IUGA/ICS classification system for mesh erosion.
AB  - AIMS: Our aim was to assess the usability of the IUGA/ICS classification system
      for mesh erosion in a tertiary clinical practice and to determine if assigned
      classification is associated with patient symptoms, treatment, and outcome.
      METHODS: We retrospectively identified women who had mesh erosion after prolapse
      or incontinence surgery. Each erosion was classified using the IUGA/ICS category
      time site (CTS) system. Associations between classification and presenting
      symptom (asymptomatic, pain, bleeding, voiding, or defecatory dysfunction,
      infection, prolapse), treatment type, and outcome were evaluated with chi-squared
      test, student's t-test, and univariate logistic regression. RESULTS: We
      identified 74 subjects with mesh erosion; only 70% were classifiable.
      Asymptomatic patients (n = 19) (Category A) were more likely to be managed
      conservatively (P = 0.001). Symptomatic patients (n = 55) (Category B) were more
      likely to be managed surgically (P = 0.003). Other variables had no association
      with treatment. No variables were associated with outcome. Presenting symptom was
      associated with both treatment (P = 0.005) and outcome (P = 0.03). Asymptomatic
      subjects were more likely to have satisfactory outcome (P = 0.03). Urinary
      frequency and urgency were highly correlated with surgical management (P = 0.02).
      CONCLUSIONS: One third of mesh erosions could not be retrospectively coded using
      the IUGA/ICS classification. The components of the system were not predictive of
      treatment nor outcome with exception of the Category A (asymptomatic) and
      Category B (symptomatic). Asymptomatic women with mesh erosion can be
      successfully managed with conservative measures. Use of a classification system
      may be enhanced if the system is simplified by limiting the number of variables
      to those associated with interventions and patient outcome. Neurourol. Urodynam.
      35:589-594, 2016. (c) 2015 Wiley Periodicals, Inc.

PMID- 25874640
TI  - Three-dimensional photoacoustic endoscopic imaging of the rabbit esophagus.
AB  - We report photoacoustic and ultrasonic endoscopic images of two intact rabbit
      esophagi. To investigate the esophageal lumen structure and microvasculature, we
      performed in vivo and ex vivo imaging studies using a 3.8-mm diameter
      photoacoustic endoscope and correlated the images with histology. Several
      interesting anatomic structures were newly found in both the in vivo and ex vivo
      images, which demonstrates the potential clinical utility of this endoscopic
      imaging modality. In the ex vivo imaging experiment, we acquired high-resolution
      motion-artifact-free three-dimensional photoacoustic images of the vasculatures
      distributed in the walls of the esophagi and extending to the neighboring
      mediastinal regions. Blood vessels with apparent diameters as small as 190 MUm
      were resolved. Moreover, by taking advantage of the dual-mode high-resolution
      photoacoustic and ultrasound endoscopy, we could better identify and characterize
      the anatomic structures of the esophageal lumen, such as the mucosal and
      submucosal layers in the esophageal wall, and an esophageal branch of the
      thoracic aorta. In this paper, we present the first photoacoustic images showing
      the vasculature of a vertebrate esophagus and discuss the potential clinical
      applications and future development of photoacoustic endoscopy. 

PMID- 25874641
TI  - Physical education: the effect of epoch lengths on children's physical activity
      in a structured context.
AB  - BACKGROUND: Despite a consensus emerging that affirms that shorter epochs should
      be used in youth to correctly register physical activity levels in free-living
      conditions, little is known about its effect on children's physical activity
      conducted in structured periods of time. This study analyzed the effect that
      epoch length (1, 2, 3, 5, 10, 15, 30 and 60s) may have on different physical
      activity intensities in physical education lessons. METHODS: A sample of 1912
      individual measures of physical education lessons were measured with a GT3X
      accelerometer. Data were collected from 1227 Swiss Elementary school students
      recruited in 17 elementary schools. PE lessons lasted from 45 minutes to one and
      a half hours. Data, originally collected in 1-s epoch, were then reintegrated
      into 2s, - 3s - 5s - 10s - 15s - 30s -60s epochs. RESULTS: Longer epochs were
      associated with higher levels of light (F = 8197.6, p < .001), moderate (F =
      2708.17, p < .001), and moderate-to-vigorous physical activity (F = 888.08, p <
      .001). However, longer epochs showed lower levels of sedentary activity (F =
      31714.33, p < .001) and vigorous physical activity (F = 1910.97, p < .001). Bias
      increased in all PA intensities when shorter epochs were compared with longer
      epochs. There were statistically significant differences in compliance with
      physical education guidelines (chi(2) = 989.27, p<.001), showing higher levels
      with longer epochs. CONCLUSION: PA context may have some influence on the effects
      that epoch length have on PA estimates, more specifically on MVPA. Nevertheless,
      the use of a high-frequency sampling interval should be used to more accurately
      assess children's PA.

PMID- 25874642
TI  - Rationale for WHO's new position calling for prompt reporting and public
      disclosure of interventional clinical trial results.

PMID- 25874643
TI  - Hantaan virus surveillance targeting small mammals at nightmare range, a high
      elevation military training area, Gyeonggi Province, Republic of Korea.
AB  - Rodent-borne disease surveillance was conducted at Nightmare Range (NM-R), near
      the demilitarized zone in northeast Gyeonggi Province, Republic of Korea, to
      identify hemorrhagic fever with renal syndrome (HFRS) risks for a mountainous
      high-elevation (500 m) military training site. Monthly surveys were conducted
      from January 2008-December 2009. A total of 1,720 small mammals were captured
      belonging to the Orders Rodentia [Families, Sciuridae (1 species) and Muridae (7
      species)] and Soricomorpha [Family, Soricidae (1species)]. Apodemus agrarius, the
      primary reservoir for Hantaan virus (HTNV), accounted for 89.9% (1,546) of all
      small mammals captured, followed by Myodes regulus (4.0%), Crocidura lasiura
      (3.9%), Micromys minutus (1.4%), Mus musculus (0.3%), Microtus fortis (0.2%),
      Apodemus peninsulae (0.2%), Tamias sibiricus (0.1%), and Rattus norvegicus
      (<0.1%). Three species were antibody-positive (Ab+) for hantaviruses: A. agrarius
      (8.2%), M. minutus (4.2%), and C. lasiura (1.5%). HTNV specific RNA was detected
      in 93/127 Ab+ A. agrarius, while Imjin virus specific RNA was detected in 1/1 Ab+
      C. lasiura. Overall, hantavirus Ab+ rates for A. agrarius increased with weight
      (age) and were significantly higher among males (10.9%) than females (5.1%)
      (P<0.0001). High A. agrarius gravid rates during the fall (August-September) were
      associated with peak numbers of HFRS cases in Korea that followed high gravid
      rates. From 79 RT-PCR positive A. agrarius, 12 HTNV RNA samples were sequenced
      and compared phylogenetically based on a 320 nt sequence from the GC glycoprotein
      encoding M segment. These results demonstrate that the HTNV isolates from NM-R
      are distinctly separated from HTNV isolated from the People's Republic of China.
      These studies provide for improved disease risk assessments that identify
      military activities, rodent HTNV rates, and other factors associated with the
      transmission of hantaviruses during field training exercises. 

PMID- 25874644
TI  - Patient Symptomatology in Anal Dysplasia.
AB  - IMPORTANCE: High-resolution anoscopy (HRA) is becoming increasingly advocated as
      a method of screening for anal dysplasia in high-risk patients. OBJECTIVE: To
      describe, through HRA findings, the association between patient symptomatology
      and anal dysplasia among patients at high risk for anal dysplasia. DESIGN,
      SETTING, AND PARTICIPANTS: Univariable and multivariable analyses were conducted
      of data from a prospectively maintained HRA database on all patients undergoing
      HRA with biopsy from November 1, 2011, to March 13, 2014, at a tertiary care HRA
      clinic. Data included demographics, medical history and comorbidities, HIV status
      and related measures (CD4 cell counts, HIV viral load, and use of highly active
      antiretroviral therapy), sexual orientation (when available), patient symptoms at
      initial presentation, physical examination findings, anal Papanicolaou (Pap)
      smear findings. MAIN OUTCOMES AND MEASURES: High-resolution anoscopy diagnosis of
      high- vs low-grade dysplasia or no dysplasia. RESULTS: One hundred sixty-one HRA
      biopsy specimens (mean [SEM], 1.77 [0.11] biopsy specimens per patient) were
      obtained from 91 patients (mean [SEM] age, 45.7 [1.2] years; 61 men [67%]; 47
      black patients [52%]; and 70 human immunodeficiency virus-positive patients
      [77%]). Twenty-seven patients (30%) had high-grade dysplasia, 26 had low-grade
      dysplasia (29%), and 38 had no dysplasia (42%). The majority of patients (63
      [69%]) were asymptomatic (anal pain, 11 [12%]; bleeding, 14 [15%]; and pruritus,
      10 [11%]). Forty-one patients (45%) presented with anal pain (odds ratio, 5.25;
      95% CI, 1.44-21.82; P = .02), and patients with either high- or low-grade
      dysplasia were more likely to present with anal lesions on physical examination
      compared with patients without dysplasia (odds ratio, 4.34; 95% CI, 1.78-11.20; P
      = .002). Multivariable analysis suggested that anal pain was independently
      associated with high-grade dysplasia (odds ratio, 6.42; 95% CI, 1.18-43.3; P =
      .03). CONCLUSIONS AND RELEVANCE: Anal dysplasia is a silent disease that is
      frequently asymptomatic. However, patients with anal pain, anal lesions, and
      other high-risk factors are at increased risk of having high-grade anal
      dysplasia. These patients may benefit from routine screening with HRA.

PMID- 25874645
TI  - Effects of exercise accumulation on plasma lipids and lipoproteins.
AB  - Debate exists as to whether improvements in some cardiometabolic risk factors
      following exercise training result more from the last session of, or from an
      accumulation of, exercise sessions. This study was designed to compare the effect
      of a single exercise session with 3 consecutive days of exercise on triglyceride
      (TG), high-density lipoprotein-cholesterol (HDL-C), and low-density lipoprotein
      cholesterol (LDL-C). Twelve young adult (aged 22.5+/-2.5 years), overweight (body
      mass index=29.7+/-4 kg.m(-2)), sedentary, black (n=5) and white (n=7) men (n=6)
      and women (n=6) completed, in random order, a single treadmill exercise session
      at 60% maximal oxygen uptake for 90 min (1EX), accumulated exercise sessions
      (same as for 1EX) for 3 consecutive days (3EX), and a control protocol (no
      exercise for 6 days). Plasma samples were collected from baseline through 24, 48,
      and 72 h postexercise. Significant treatment-by-time interactions (p<0.05)
      existed in HDL-C and LDL-C. Postexercise responses of HDL-C differed at 48 h
      (1EX: -3.6, 3EX: +3.7 mg.dL(-1)) and 72 h (1EX: -1.7, 3EX: +3.2 mg.dL(-1)). LDL-C
      responses differed at 48 h (1EX: -16, 3EX: +6 mg.dL(-1)). Although not
      statistically significant, TG concentrations decreased by 29% at 24 h after 3EX,
      compared with -7% after 1EX. An inverse relationship between baseline and
      postexercise reduction in TG was present with 3EX (r=-0.655; p<0.05). In
      conclusion, 3EX increased HDL-C and decreased TG more than 1EX, while the
      decrease in LDL-C after 1EX was suppressed. Blood lipid panel changes may be due
      to more accumulated effects over time rather than just a result of the most
      recent exercise session.

PMID- 25874646
TI  - On-line hydrogen-isotope measurements of organic samples using elemental
      chromium: an extension for high temperature elemental-analyzer techniques.
AB  - The high temperature conversion (HTC) technique using an elemental analyzer with
      a glassy carbon tube and filling (temperature conversion/elemental analysis,
      TC/EA) is a widely used method for hydrogen isotopic analysis of water and many
      solid and liquid organic samples with analysis by isotope-ratio mass spectrometry
      (IRMS). However, the TC/EA IRMS method may produce inaccurate delta(2)H results,
      with values deviating by more than 20 mUr (milliurey = 0.001 = 10/00) from the
      true value for some materials. We show that a single-oven, chromium-filled
      elemental analyzer coupled to an IRMS substantially improves the measurement
      quality and reliability for hydrogen isotopic compositions of organic substances
      (Cr-EA method). Hot chromium maximizes the yield of molecular hydrogen in a
      helium carrier gas by irreversibly and quantitatively scavenging all reactive
      elements except hydrogen. In contrast, under TC/EA conditions, heteroelements
      like nitrogen or chlorine (and other halogens) can form hydrogen cyanide (HCN) or
      hydrogen chloride (HCl) and this can cause isotopic fractionation. The Cr-EA
      technique thus expands the analytical possibilities for on-line hydrogen-isotope
      measurements of organic samples significantly. This method yielded
      reproducibility values (1-sigma) for delta(2)H measurements on water and caffeine
      samples of better than 1.0 and 0.5 mUr, respectively. To overcome handling
      problems with water as the principal calibration anchor for hydrogen isotopic
      measurements, we have employed an effective and simple strategy using reference
      waters or other liquids sealed in silver-tube segments. These crimped silver
      tubes can be employed in both the Cr-EA and TC/EA techniques. They simplify
      considerably the normalization of hydrogen-isotope measurement data to the VSMOW
      SLAP (Vienna Standard Mean Ocean Water-Standard Light Antarctic Precipitation)
      scale, and their use improves accuracy of the data by eliminating evaporative
      loss and associated isotopic fractionation while handling water as a bulk sample.
      The calibration of organic samples, commonly having high delta(2)H values, will
      benefit from the availability of suitably (2)H-enriched reference waters,
      extending the VSMOW-SLAP scale above zero. 

PMID- 25874647
TI  - Eating Disorders: Cultural Model and Consensus Regarding Food.
AB  - The cultural model of food was applied to 112 adult patients with eating
      disorders (PG) and 36 healthy adult women (CG) of similar age. The Free List and
      Ranking of Foods was used to group foods and verify consensus and cultural
      aspects. Calories, health, and taste were the dimensions used by the participants
      to group the foods, and strong consensus was achieved in regard to calories and
      health. There were, however, inter- and intra-group divergences in regard to
      these ideas, especially in the PG. The CG used distinct criteria, showing a more
      complex model. 

PMID- 25874648
TI  - Microbiological changes and biodiversity of cultivable indigenous bacteria in
      Sanbao larger yellow croaker (Pseudosciaena crocea), a Chinese salted and
      fermented seafood.
AB  - Sanbao large yellow croaker is a kind of Chinese salted and fermented seafood
      processed by adding 50% of salt and fermenting at high temperature [around 30 
      degrees C] over 20 d. To get a comprehensive understanding of cultivable
      microorganism's diversity present in its fermentation, the chemical and microbial
      properties of this product, were detected initially, followed by identification
      of bacteria recovered from different fermentation periods using PCR-RFLP and 16S
      rRNA gene sequencing analysis. In total, 105 indigenous isolates were recovered
      with 3 different medium and majority of the isolates picked up from both MRS and
      MSA medium were finally clustered into the genus of Staphylococcus (S.). Among
      the 90 Staphylococci, S. xylosus, S. saprophyticus, and S. nepalensis were the
      most prevailing cultivable species recovered throughout the whole production
      process (70 isolates, 77.8%), while 5 other species, namely, S. aureus, S.
      vitulinus, S. sciuri, S. equorum, and S. succinus formed a minor fraction (20
      isolates, 22.2%) of the Staphylococcus communities. Lactic acid bacteria,
      Pseudomonas, Proteus, and Bacillus constituted trivial populations in the initial
      period of the fermentation and then gave the way to the Staphylococcus
      immediately. High salt concentration used during the processing is like to have a
      pronounced influence on the microbial populations involved. Data obtained in this
      work could be referred in control and optimization of the fermentation process
      and selecting suitable strains for aquatic product fermentation. 

PMID- 25874649
TI  - Renal impairment in cirrhosis unrelated to hepatorenal syndrome.
AB  - Renal impairment is common in liver disease and may occur as a consequence of the
      pathophysiological changes that underpin cirrhosis or secondary to a pre-existing
      unrelated insult. Nevertheless, the onset of renal impairment often portends a
      worsening prognosis. Hepatorenal syndrome remains one of the most recognized and
      reported causes of renal impairment in cirrhosis. However, other causes of renal
      impairment occur and can be classified into prerenal, intrinsic or postrenal,
      which are the subjects of the present review. 

PMID- 25874650
TI  - Characterization of inflammatory bowel disease in elderly hospitalized patients
      in a large central Canadian Health region.
AB  - OBJECTIVE: To determine differences in phenotype and treatment among hospitalized
      elderly and young patients with inflammatory bowel disease (IBD), and the utility
      of International Classification of Diseases, 10th Revision (ICD)-10 codes in
      hospital discharge abstracts in diagnosing IBD in elderly patients. METHODS: A
      large Canadian health region hospitalization discharge database was used to
      identify elderly (>65 years of age) and young (19 to 50 years of age) patients
      with IBD admitted between April 1, 2007 and March 31, 2012, and a random sample
      of elderly patients with other colonic conditions. Medical records were reviewed
      to confirm IBD diagnosis and extract clinical information. The characteristics of
      elderly versus young hospitalized IBD patients and accuracy of ICD-10 IBD
      discharge codes in the elderly were assessed. RESULTS: One hundred forty-three
      elderly and 82 young patients with an IBD discharge diagnosis, and 135 elderly
      patients with other gastrointestinal discharge diagnoses were included. Elderly
      IBD patients were less likely to have ileocolonic Crohn disease (21.4% versus
      50.9%; P=0.001), more likely to be prescribed 5-aminosalicylates (61% versus 43%;
      P=0.04), and less likely to be prescribed biologics (6% versus 21%; P=0.016) or
      immunomodulators (21% versus 42%; P=0.01). The sensitivity, specificity and
      positive predictive value of a single ICD code for CD were 98%, 96% and 94%,
      respectively, and for ulcerative colitis (UC) were 98%, 92% and 70%,
      respectively. CONCLUSIONS: Treatment approaches in elderly patients were
      different than in younger IBD patients despite having disease sufficiently severe
      to require hospitalization. While less accurate in UC, a single ICD-10 IBD code
      was sufficient to identify elderly CD and UC hospitalized patients.

PMID- 25874651
TI  - Rate, delay and predictors of hepatitis C treatment in British Columbia.
AB  - BACKGROUND: The current treatment rate for chronic hepatitis C virus (HCV)
      infection is suboptimal despite the availability of efficacious antiviral
      therapy. OBJECTIVE: To determine the rate, delay and predictors of treatment in
      patients with chronic HCV infection. METHODS: A retrospective chart review of
      chronic HCV patients who were being evaluated at a tertiary hepatology centre in
      Vancouver, British Columbia, was performed. RESULTS: One hundred sixty-four
      patients with chronic HCV infection who were assessed for treatment between
      February 2008 and January 2013 were reviewed. Treatment was initiated in 25.6%
      (42 of 164). In multivariate analyses, male sex (OR 7.90 [95% CI 1.35 to 46.15])
      and elevated alanine aminotransferase (ALT) level (>1.5 times the upper limit of
      normal) (OR 3.10 [95% CI 1.32 to 7.27]) were positive predictors of treatment,
      whereas active smoking (OR 0.09 [95% CI 0.02 to 0.53]) and Charlson comorbidity
      index (per point increase) (OR 0.47 [95% CI 0.27 to 0.83]) were negative
      predictors of treatment. The most common reasons for treatment deferral were no
      or minimal liver fibrosis in 57.7% (n=30), persistently normal ALT levels in
      57.7% (n=30) and patient unreadiness in 28.8% (n=15). The most common reasons for
      treatment noninitiation were patient refusal in 59.1% (n=26), medical
      comorbidities in 36.4% (n=16), psychiatric comorbidities in 9.1% (n=4) and
      decompensated cirrhosis in 9.1% (n=4). There was a statistically significant
      difference in the median time delay from HCV diagnosis to general practitioner
      referral between the treated and untreated patients (66.3 versus 119.5 months,
      respectively [P=0.033]). The median wait time from general practitioner referral
      to hepatologist consult was similar between the treated and untreated patients
      (1.7 months versus 1.5 months, respectively [P=0.768]). Among the treated
      patients, the median time delay was 6.8 months from hepatologist consult to
      treatment initiation. CONCLUSIONS: The current treatment rate for chronic HCV
      infection remains suboptimal. Medical and psychiatric comorbidities represent a
      major obstacle to HCV treatment. Minimal hepatic fibrosis may no longer be a
      major reason for treatment deferral as more efficacious and tolerable antiviral
      therapies become available in the future. Greater educational initiatives for
      primary care physicians would promote early referral of patients. More nursing
      support would alleviate the backlog of patients awaiting treatment.

PMID- 25874652
TI  - Amine-terminated monolayers on carbon: preparation, characterization, and
      coupling reactions.
AB  - Aminophenyl and aminomethylphenyl monolayers have been electrografted to glassy
      carbon and pyrolyzed photoresist film from the corresponding diazonium ions using
      a protection-deprotection strategy based on Boc (tert-butyloxycarbonyl) and Fmoc
      (fluorenylmethyloxycarbonyl) groups. After grafting and then deprotecting films
      of Boc-NH-Ar, Fmoc-NH-Ar, and Fmoc-NH-CH2-Ar, depth profiling by atomic force
      microscopy confirmed that the resulting amine-terminated films were monolayers.
      In contrast, after deprotection, Boc-NH-CH2-Ar gave a multilayer film.
      Electroactive carboxylic acid derivatives were coupled to the monolayers through
      amide linkages. Electrochemical measurements revealed that the deprotected Fmoc
      NH-CH2-Ar monolayer gave the highest surface concentration of coupled nitrophenyl
      and ferrocenyl groups and DFT calculations established that this monolayer has
      the highest theoretical surface concentration of those examined. 

PMID- 25874653
TI  - Programmable DNA-Mediated Multitasking Processor.
AB  - Because of DNA appealing features as perfect material, including minuscule size,
      defined structural repeat and rigidity, programmable DNA-mediated processing is a
      promising computing paradigm, which employs DNAs as information storing and
      processing substrates to tackle the computational problems. The massive
      parallelism of DNA hybridization exhibits transcendent potential to improve
      multitasking capabilities and yield a tremendous speed-up over the conventional
      electronic processors with stepwise signal cascade. As an example of multitasking
      capability, we present an in vitro programmable DNA-mediated optimal route
      planning processor as a functional unit embedded in contemporary navigation
      systems. The novel programmable DNA-mediated processor has several advantages
      over the existing silicon-mediated methods, such as conducting massive data
      storage and simultaneous processing via much fewer materials than conventional
      silicon devices. 

PMID- 25874654
TI  - The economic impact of moderate stage Alzheimer's disease in Italy: evidence from
      the UP-TECH randomized trial.
AB  - BACKGROUND: There is consensus that dementia is the most burdensome disease for
      modern societies. Few cost-of-illness studies examined the complexity of
      Alzheimer's disease (AD) burden, considering at the same time health and social
      care, cash allowances, informal care, and out-of-pocket expenditure by families.
      METHODS: This is a comprehensive cost-of-illness study based on the baseline data
      from a randomized controlled trial (UP-TECH) enrolling 438 patients with moderate
      AD and their primary caregiver living in the community. RESULTS: The societal
      burden of AD, composed of public, patient, and informal care costs, was about
      ?20,000/yr. Out of this, the cost borne by the public sector was ?4,534/yr. The
      main driver of public cost was the national cash-for-care allowance (?2,324/yr),
      followed by drug prescriptions (?1,402/yr). Out-of-pocket expenditure
      predominantly concerned the cost of private care workers. The value of informal
      care peaked at ?13,590/yr. Socioeconomic factors do not influence AD public cost,
      but do affect the level of out-of-pocket expenditure. CONCLUSION: The burden of
      AD reflects the structure of Italian welfare. The families predominantly manage
      AD patients. The public expenditure is mostly for drugs and cash-for-care
      benefits. From a State perspective in the short term, the advantage of these care
      arrangements is clear, compared to the cost of residential care. However, if
      caregivers are not adequately supported, savings may be soon offset by higher
      risk of caregiver morbidity and mortality produced by high burden and stress. The
      study has been registered on the website www.clinicaltrials.org ( TRIAL
      REGISTRATION NUMBER: NCT01700556).

PMID- 25874655
TI  - Efficient Visible Light Nitrogen Fixation with BiOBr Nanosheets of Oxygen
      Vacancies on the Exposed {001} Facets.
AB  - Even though the well-established Haber-Bosch process has been the major
      artificial way to "fertilize" the earth, its energy-intensive nature has been
      motivating people to learn from nitrogenase, which can fix atmospheric N2 to NH3
      in vivo under mild conditions with its precisely arranged proteins. Here we
      demonstrate that efficient fixation of N2 to NH3 can proceed under room
      temperature and atmospheric pressure in water using visible light illuminated
      BiOBr nanosheets of oxygen vacancies in the absence of any organic scavengers and
      precious-metal cocatalysts. The designed catalytic oxygen vacancies of BiOBr
      nanosheets on the exposed {001} facets, with the availability of localized
      electrons for pi-back-donation, have the ability to activate the adsorbed N2,
      which can thus be efficiently reduced to NH3 by the interfacial electrons
      transferred from the excited BiOBr nanosheets. This study might open up a new
      vista to fix atmospheric N2 to NH3 through the less energy-demanding
      photochemical process. 

PMID- 25874656
TI  - Identification of nitrogen starvation-responsive microRNAs in Chrysanthemum
      nankingense.
AB  - MicroRNA (miRNA) is involved in many developmental processes and various abiotic
      stress responses in plants. As nitrogen is a limited element for plant growth,
      comparative analyses of miRNAs responding to low nitrogen stress is important for
      improving the nitrogen use efficiency (NUE). We used high-throughput sequencing
      to detect the response of miRNAs to low nitrogen stress in the roots and leaves
      of Chrysanthemum nankingense. Compared with the control, the differential
      expression was more than 2-fold in 81 miRNAs in roots and 101 miRNAs in leaves.
      The identified miRNAs showed overlapping or unique response to nitrate limitation
      in roots and leaves, including several members of known miRNA families with low
      nitrogen stress response, such as miR156, miR169, and miR393. The potential
      target genes of these miRNAs were also identified. The total amount of predicted
      target genes was 219, and the corresponding amount of matched miRNAs was 37 in
      roots and 44 in leaves. Moreover, we used 5' RLM-RACE to map the cleavage sites
      in four predicted target genes. The differential expression level of miRNAs and
      target genes was verified by quantitative real-time polymerase chain reaction
      (qRT-PCR). According to the functional characteristics of the predicted target
      genes, they were divided into three main categories: transcription factors,
      kinases, and metabolism. 

PMID- 25874657
TI  - Heterologous expression of the halophyte Zoysia matrella H+-pyrophosphatase gene
      improved salt tolerance in Arabidopsis thaliana.
AB  - A number of vacuolar H(+)-pyrophosphatase (VP) family genes play important roles
      in plant growth under salt stress condition. Despite their biological importance
      in plant salt-stress regulation, there is no report about VP in the halophytic
      turfgrass Zoysia matrella. Here, we isolated ZmVP1, a type I VP homologues gene
      encoding 768 amino acids by using the degenerated PCR and RACE PCR methods from
      Zoysia matrella. The expression level of ZmVP1 was significantly induced by
      salinity, drought and cold, but not by heat. ZmVP1 can restore the salt-tolerant
      ability of a salt-sensitive yeast strain. Overexpression of ZmVP1 in Arabidopsis
      thaliana resulted in more vigorous growth under salt stress. Moreover, the
      transgenic Arabidopsis accumulated more Na(+) and K(+) in the leaves compared to
      that of wild type plants under salt stress, had higher activities of V-ATPase and
      V-PPase, and showed higher relative gene expression levels of 5 stress-related
      genes (AtNHX1, AtLEA, AtP5CS, AtMn-SOD, AtAPX1). These results demonstrated that
      ZmVP1 from Z. matrella was a functional tonoplast H(+)-pyrophosphatase
      contributing to salt tolerance potentially through regulating the Na(+)
      compartment in vacuole, K(+) assimilation, osmotic regulation and antioxidant
      response. 

PMID- 25874658
TI  - Marine hydrocarbonoclastic bacteria as whole-cell biosensors for n-alkanes.
AB  - Whole-cell biosensors offer potentially useful, cost-effective systems for the in
      situ monitoring of seawater for hydrocarbons derived from accidental spills. The
      present work compares the performance of a biosensor system for the detection of
      alkanes in seawater, hosted in either Escherichia coli (commonly employed in
      whole-cell biosensors but not optimized for alkane assimilation) or different
      marine bacteria specialized in assimilating alkanes. The sensor system was based
      on the Pseudomonas putida AlkS regulatory protein and the PalkB promoter fused to
      a gene encoding the green fluorescent protein. While the E. coli sensor provided
      the fastest response to pure alkanes (25-fold induction after 2 h under the
      conditions used), a sensor based on Alcanivorax borkumensis was slower, requiring
      3-4 h to reach similar induction values. However, the A. borkumensis sensor
      showed a fourfold lower detection threshold for octane (0.5 MUM), and was also
      better at sensing the alkanes present in petrol. At petrol concentrations of
      0.0125%, the A. borkumensis sensor rendered a sevenfold induction, while E. coli
      sensor showed no response. We discuss possible explanations to this behaviour in
      terms of the cellular adaptations to alkane uptake and the basal fluorescence
      produced by each bacterial strain, which was lowest for A. borkumensis. 

PMID- 25874660
TI  - Bioimaging application of a novel anion selective chemosensor derived from
      vitamin B6 cofactor.
AB  - The detection of intracellular fluoride was achieved by a novel Schiff base
      chemosensor derived from vitamin B6 cofactor (L) using fluorescence imaging
      technique. The sensor L was synthesized by condensation of pyridoxal phosphate
      with 2-aminothiophenol. The anion recognition ability of L was explored by UV-Vis
      and fluorescence methods in DMSO and mixed DMSO-H2O system. The sensor L showed
      both naked-eye detectable color change from colorless to light green and
      remarkable fluorescence enhancement at 500 nm in the presence of F(-) and AcO(-).
      The anion recognition was occurred through the formation of hydrogen bonded
      complexes between these anions and L, followed by the partial deprotonation of L.
      The detection limit of L for the analysis of F(-) and AcO(-) was calculated to be
      1.88 MUM and 9.10 MUM, respectively. Finally, the detection of cytoplasmic
      fluoride was tested using human cancer cell HeLa through fluorescence imaging.

PMID- 25874659
TI  - Treatment of vaginal candidiasis for the prevention of preterm birth: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Recognition that ascending infection leads to preterm birth has led
      to a number of studies that have evaluated the treatment of vaginal infections in
      pregnancy to reduce preterm birth rates. However, the role of candidiasis is
      relatively unexplored. Our aim was to undertake a systematic review and meta
      analysis to assess whether treatment of pregnant women with vulvovaginal
      candidiasis reduces preterm birth rates and other adverse birth outcomes.
      METHODS: We undertook a systematic review and meta-analysis of published
      randomised controlled trials (RCTs) in which pregnant women were treated for
      vulvovaginal candidiasis (compared to placebo or no treatment) and where preterm
      birth was reported as an outcome. Trials were identified by searching the
      Cochrane Central Register of Controlled Trials, Medline and Embase databases to
      January 2014. Trial eligibility and outcomes were pre-specified. Two reviewers
      independently assessed the studies against the agreed criteria and extracted
      relevant data using a standard data extraction form. Meta-analysis was used to
      calculate pooled rate ratios (RR) and 95% confidence intervals (CI) using a fixed
      effects model. RESULTS: There were two eligible RCTs both among women with
      asymptomatic candidiasis, with a total of 685 women randomised. Both trials
      compared treatment with usual care (no screening for, or treatment of,
      asymptomatic candidiasis). Data from one trial involved a post-hoc subgroup
      analysis (n = 586) of a larger trial of treatment of 4,429 women with
      asymptomatic infections in pregnancy and the other was a pilot study (n = 99).
      There was a significant reduction in spontaneous preterm births in treated
      compared with untreated women (meta-analysis RR = 0.36, 95% CI = 0.17 to 0.75).
      Other outcomes were reported by one or neither trial. CONCLUSIONS: This
      systematic review found two trials comparing the treatment of asymptomatic
      vaginal candidiasis in pregnancy for the outcome of preterm birth. Although the
      effect estimate suggests that treatment of asymptomatic candidiasis may reduce
      the risk of preterm birth, the result needs to be interpreted with caution as the
      primary driver for the pooled estimate comes from a post-hoc (unplanned) subgroup
      analysis. A prospective trial with sufficient power to answer the clinical
      question 'does treatment of asymptomatic candidiasis in early pregnancy prevent
      preterm birth' is warranted. SYSTEMATIC REVIEW REGISTRATION: PROSPERO
      CRD42014009241.

PMID- 25874661
TI  - Inactivation and regrowth of multidrug resistant bacteria in urban wastewater
      after disinfection by solar-driven and chlorination processes.
AB  - Solar disinfection and solar-driven advanced oxidation processes (AOPs) (namely
      H2O2/sunlight, TiO2/sunlight, H2O2/TiO2/sunlight, solar photo-Fenton) were
      evaluated in the inactivation of indigenous antibiotic-resistant bacteria (ARB)
      in real urban wastewater. A multidrug resistant (MDR) Escherichia coli strain
      isolated from the effluent of the biological process of an urban wastewater
      treatment plant was the target ARB. The higher inactivation rates (residual
      density under detection limit, 2 CFUm L(-1)) were achieved with
      H2O2/TiO2/sunlight (cumulative energy per unit of volume (QUV) in the range 3-5
      kJ L(-1), depending on H2O2/TiO2 ratio) and H2O2/sunlight (QUV of 8 kJ L(-1))
      processes. All investigated processes did not affect antibiotic resistance of
      survived colonies. Moreover, H2O2/sunlight was compared with conventional
      chlorination process to evaluate bacterial regrowth potential and particularly
      the proportion of indigenous MDR E. coli with respect to total indigenous E. coli
      population. Chlorination (1.0 mg Cl2 L(-1)) was more effective than H2O2/sunlight
      (50 mg H2O2 L(-1)) to achieve total inactivation of MDR E. coli (15 min Vs 90
      min) but less effective in controlling their regrowth (24 h Vs 48 h).
      Interestingly, the percentage of MDR E. coli in H2O2/sunlight treated samples
      decreased as incubation time increased; the opposite was observed for chlorinated
      samples.

PMID- 25874662
TI  - Photodamage attenuation effect by a tetraprenyltoluquinol chromane meroterpenoid
      isolated from Sargassum muticum.
AB  - A tetraprenyltoluquinol meroterpenoid with a chromane moiety, obtained as an
      epimeric mixture at C3, was isolated for the first time from the dichloromethane
      fraction of a methanolic extract from the brown alga Sargassum muticum. The
      structure has been established by means of spectral methods including NMR
      spectroscopy and MS and comparison with reported data. The compound showed
      photodamage attenuation on irradiated cells with UVA light, presented protection
      against intracellular ROS generation in a degree comparable to retinoic acid (9.1
      20.6%) and did not display toxicity against human dermal fibroblast cells. 

PMID- 25874663
TI  - Variations of Flame Retardant, Polycyclic Aromatic Hydrocarbon, and Pesticide
      Concentrations in Chicago's Atmosphere Measured using Passive Sampling.
AB  - Atmospheric concentrations of flame retardants, polycyclic aromatic hydrocarbons,
      and pesticides were measured using passive air samplers equipped with
      polyurethane foam disks to find spatial information in and around Chicago,
      Illinois. Samplers were deployed around the greater Chicago area for intervals of
      6 weeks from 2012 to 2013 (inclusive). Volumes were calculated using passive
      sampling theory and were based on meteorology and the compounds' octanol-air
      partition coefficients. Geometric mean concentrations of total polybrominated
      diphenyl ethers ranged from 11 to 150 pg/m3, and tributyl phosphate, tris(2
      chloroethyl)phosphate, tris(1-chloro-2-propyl)phosphate, and triphenyl phosphate
      concentrations were in the ranges of 54-290, 32-340, 130-580, and 170-580 pg/m3,
      respectively. The summed concentrations of 16 PAHs ranged from 8700 to 52,000
      pg/m3 over the sampling area, and DDT, chlordane, and endosulfan concentrations
      were in the ranges of 2.7-9.9, 8.2-66, and 16-85 pg/m3, respectively. Sampling
      sites were split into two groups depending on their distances from the Illinois
      Institute of Technology campus in Chicago. With a few exceptions, the
      concentrations of most compound groups in the city's center were the same or
      slightly higher than those measured >45 km away. The data also showed that the
      concentrations measured with a passive atmospheric sampling system are in good
      agreement with those measured with an active, high-volume, sampling system. Given
      that the sampling times are different (passive, 43 days; active, 1 day), and that
      both of these measured concentrations cover about 5 orders of magnitude, the
      agreement between these passive and active sampling methods is excellent.

PMID- 25874664
TI  - Effect of body mass and clothing on carrion entomofauna.
AB  - Carcass mass largely affects pattern and rate of carrion decomposition.
      Supposedly, it is similarly important for carrion entomofauna; however, most of
      its likely effects have not been tested experimentally. Here, simultaneous
      effects of carcass mass and clothing are analyzed. A factorial block experiment
      with four levels of carcass mass (small carcasses 5-15 kg, medium carcasses 15.1
      30 kg, medium/large carcasses 35-50 kg, large carcasses 55-70 kg) and two levels
      of carcass clothing (clothed and unclothed) was made in a grassland habitat of
      Western Poland. Pig carcasses (N = 24) were grouped into spring, early summer,
      and late summer blocks. Insects were sampled manually and with pitfall traps.
      Results demonstrate that insect assemblages are more complex, abundant, and long
      lasting on larger carcasses, whereas clothing is of minor importance in this
      respect. Only large or medium/large carcasses were colonized by all guilds of
      carrion insects, while small or medium carcasses revealed high
      underrepresentation of late-colonizing insects (e.g., Cleridae or Nitidulidae).
      This finding indicates that carcasses weighing about 23 kg-a standard in forensic
      decomposition studies-give an incomplete picture of carrion entomofauna.
      Residencies of all forensically relevant insects were distinctly prolonged on
      larger carcasses, indicating that cadaver mass is a factor of great importance in
      this respect. The pre-appearance interval of most taxa was found to be unrelated
      to mass or clothing of a carcass. Moreover, current results suggest that rate of
      larval development is higher on smaller carcasses. In conclusion, this study
      demonstrates that carcass mass is a factor of crucial importance for carrion
      entomofauna, whereas the importance of clothing is small.

PMID- 25874665
TI  - Traumatic injuries after mechanical cardiopulmonary resuscitation (LUCAS2): a
      forensic autopsy study.
AB  - AIM: The aim of our study was to compare traumatic injuries observed after
      cardiopulmonary resuscitation (CPR) by means of standard (manual) or assisted
      (mechanical) chest compression by Lund University Cardiopulmonary Assist System,
      2nd generation (LUCAS2) device. METHODS: A retrospective study was conducted
      including cases from 2011 to 2013, analysing consecutive autopsy reports in two
      groups of patients who underwent medicolegal autopsy after unsuccessful CPR. We
      focused on traumatic injuries from dermal to internal trauma, collecting data
      according to a standardised protocol. RESULTS: The study group was comprised of
      26 cases, while 32 cases were included in the control group. Cardiopulmonary
      resuscitation performed by LUCAS2 was longer than manual CPR performed in control
      cases (study group: mean duration 51.5 min; controls 29.4 min; p = 0.004).
      Anterior chest lesions (from bruises to abrasions) were described in 18/26
      patients in the LUCAS2 group and in 6/32 of the control group. A mean of 6.6 rib
      fractures per case was observed in the LUCAS2 group, but this was only 3.1 in the
      control group (p = 0.007). Rib fractures were less frequently observed in younger
      patients. The frequency of sternal factures was similar in both groups. A few
      trauma injuries to internal organs (mainly cardiac, pulmonary and hepatic
      bruises), and some petechiae (study 46%; control 41 %; p = 0.79) were recorded in
      both groups. CONCLUSION: LUCASTM2-CPR is associated with more rib fractures than
      standard CPR. Typical round concentric skin lesions were observed in cases of
      mechanical reanimation. No life-threatening injuries were reported. Petechiae
      were common findings.

PMID- 25874668
TI  - Effectiveness of popular weight loss diets on cardiovascular risk reduction.

PMID- 25874666
TI  - Response of forest soil euglyphid testate amoebae (Rhizaria: Cercozoa) to pig
      cadavers assessed by high-throughput sequencing.
AB  - Decomposing cadavers modify the soil environment, but the effect on soil
      organisms and especially on soil protists is still poorly documented. We
      conducted a 35-month experiment in a deciduous forest where soil samples were
      taken under pig cadavers, control plots and fake pigs (bags of similar volume as
      the pigs). We extracted total soil DNA, amplified the SSU ribosomal RNA (rRNA)
      gene V9 region and sequenced it by Illumina technology and analysed the data for
      euglyphid testate amoebae (Rhizaria: Euglyphida), a common group of protozoa
      known to respond to micro-environmental changes. We found 51 euglyphid
      operational taxonomic units (OTUs), 45 of which did not match any known sequence.
      Most OTUs decreased in abundance underneath cadavers between days 0 and 309, but
      some responded positively after a time lag. We sequenced the full-length SSU rRNA
      gene of two common OTUs that responded positively to cadavers; a phylogenetic
      analysis showed that they did not belong to any known euglyphid family. This
      study confirmed the existence of an unknown diversity of euglyphids and that they
      react to cadavers. Results suggest that metabarcoding of soil euglyphids could be
      used as a forensic tool to estimate the post-mortem interval (PMI) particularly
      for long-term (>2 months) PMI, for which no reliable tool exists.

PMID- 25874669
TI  - A report from the American Heart Association Council on Cardiovascular and Stroke
      Nursing.

PMID- 25874670
TI  - "Mediterranean" dietary pattern for the primary prevention of cardiovascular
      disease: summaries of nursing care-related systematic reviews from the Cochrane
      library.

PMID- 25874671
TI  - 20 things you didn't know about nutrition and cardiovascular disease.

PMID- 25874672
TI  - Directed evolution 2.0: improving and deciphering enzyme properties.
AB  - Directed evolution has matured to a routinely applied algorithm to tailor enzyme
      properties to meet the demands in various applications. In order to free directed
      enzyme evolution from methodological restraints and to efficiently explore its
      potential, many different strategies have been used in directed evolution
      campaigns. Analysis of directed evolution campaigns reveals that traditional
      approaches, in which several iterative rounds of diversity generation and
      screening are performed, are gradually replaced by strategies which require less
      time, less screening efforts, and generate a molecular understanding of the
      targeted properties. In this review, conceptual advances in knowledge generating
      directed evolution strategies are summarized, compared to each other and to
      traditional directed evolution strategies. Finally, a 'KnowVolution' (knowledge
      gaining directed evolution) termed strategy is proposed. 

PMID- 25874673
TI  - The Drosophila TNF receptor Grindelwald couples loss of cell polarity and
      neoplastic growth.
AB  - Disruption of epithelial polarity is a key event in the acquisition of neoplastic
      growth. JNK signalling is known to play an important part in driving the
      malignant progression of many epithelial tumours, although the link between loss
      of polarity and JNK signalling remains elusive. In a Drosophila genome-wide
      genetic screen designed to identify molecules implicated in neoplastic growth, we
      identified grindelwald (grnd), a gene encoding a transmembrane protein with
      homology to members of the tumour necrosis factor receptor (TNFR) superfamily.
      Here we show that Grnd mediates the pro-apoptotic functions of Eiger (Egr), the
      unique Drosophila TNF, and that overexpression of an active form of Grnd lacking
      the extracellular domain is sufficient to activate JNK signalling in vivo. Grnd
      also promotes the invasiveness of Ras(V12)/scrib(-/-) tumours through Egr
      dependent Matrix metalloprotease-1 (Mmp1) expression. Grnd localizes to the
      subapical membrane domain with the cell polarity determinant Crumbs (Crb) and
      couples Crb-induced loss of polarity with JNK activation and neoplastic growth
      through physical interaction with Veli (also known as Lin-7). Therefore, Grnd
      represents the first example of a TNFR that integrates signals from both Egr and
      apical polarity determinants to induce JNK-dependent cell death or tumour growth.

PMID- 25874674
TI  - Oxytocin enables maternal behaviour by balancing cortical inhibition.
AB  - Oxytocin is important for social interactions and maternal behaviour. However,
      little is known about when, where and how oxytocin modulates neural circuits to
      improve social cognition. Here we show how oxytocin enables pup retrieval
      behaviour in female mice by enhancing auditory cortical pup call responses.
      Retrieval behaviour required the left but not right auditory cortex, was
      accelerated by oxytocin in the left auditory cortex, and oxytocin receptors were
      preferentially expressed in the left auditory cortex. Neural responses to pup
      calls were lateralized, with co-tuned and temporally precise excitatory and
      inhibitory responses in the left cortex of maternal but not pup-naive adults.
      Finally, pairing calls with oxytocin enhanced responses by balancing the
      magnitude and timing of inhibition with excitation. Our results describe
      fundamental synaptic mechanisms by which oxytocin increases the salience of
      acoustic social stimuli. Furthermore, oxytocin-induced plasticity provides a
      biological basis for lateralization of auditory cortical processing. 

PMID- 25874675
TI  - CRISPR adaptation biases explain preference for acquisition of foreign DNA.
AB  - CRISPR-Cas (clustered, regularly interspaced short palindromic repeats coupled
      with CRISPR-associated proteins) is a bacterial immunity system that protects
      against invading phages or plasmids. In the process of CRISPR adaptation, short
      pieces of DNA ('spacers') are acquired from foreign elements and integrated into
      the CRISPR array. So far, it has remained a mystery how spacers are
      preferentially acquired from the foreign DNA while the self chromosome is
      avoided. Here we show that spacer acquisition is replication-dependent, and that
      DNA breaks formed at stalled replication forks promote spacer acquisition.
      Chromosomal hotspots of spacer acquisition were confined by Chi sites, which are
      sequence octamers highly enriched on the bacterial chromosome, suggesting that
      these sites limit spacer acquisition from self DNA. We further show that the
      avoidance of self is mediated by the RecBCD double-stranded DNA break repair
      complex. Our results suggest that, in Escherichia coli, acquisition of new
      spacers largely depends on RecBCD-mediated processing of double-stranded DNA
      breaks occurring primarily at replication forks, and that the preference for
      foreign DNA is achieved through the higher density of Chi sites on the self
      chromosome, in combination with the higher number of forks on the foreign DNA.
      This model explains the strong preference to acquire spacers both from high copy
      plasmids and from phages. 

PMID- 25874677
TI  - Sensory systems: The yin and yang of cortical oxytocin.

PMID- 25874676
TI  - A molecular mechanism of artemisinin resistance in Plasmodium falciparum malaria.
AB  - Artemisinins are the cornerstone of anti-malarial drugs. Emergence and spread of
      resistance to them raises risk of wiping out recent gains achieved in reducing
      worldwide malaria burden and threatens future malaria control and elimination on
      a global level. Genome-wide association studies (GWAS) have revealed parasite
      genetic loci associated with artemisinin resistance. However, there is no
      consensus on biochemical targets of artemisinin. Whether and how these targets
      interact with genes identified by GWAS, remains unknown. Here we provide
      biochemical and cellular evidence that artemisinins are potent inhibitors of
      Plasmodium falciparum phosphatidylinositol-3-kinase (PfPI3K), revealing an
      unexpected mechanism of action. In resistant clinical strains, increased PfPI3K
      was associated with the C580Y mutation in P. falciparum Kelch13 (PfKelch13), a
      primary marker of artemisinin resistance. Polyubiquitination of PfPI3K and its
      binding to PfKelch13 were reduced by the PfKelch13 mutation, which limited
      proteolysis of PfPI3K and thus increased levels of the kinase, as well as its
      lipid product phosphatidylinositol-3-phosphate (PI3P). We find PI3P levels to be
      predictive of artemisinin resistance in both clinical and engineered laboratory
      parasites as well as across non-isogenic strains. Elevated PI3P induced
      artemisinin resistance in absence of PfKelch13 mutations, but remained responsive
      to regulation by PfKelch13. Evidence is presented for PI3P-dependent signalling
      in which transgenic expression of an additional kinase confers resistance.
      Together these data present PI3P as the key mediator of artemisinin resistance
      and the sole PfPI3K as an important target for malaria elimination. 

PMID- 25874678
TI  - Microbiology: Malaria runs rings round artemisinin.

PMID- 25874679
TI  - Retraction: Histone methylation by the Drosophila epigenetic transcriptional
      regulator Ash1.

PMID- 25874680
TI  - Ordering in bio-inorganic hybrid nanomaterials probed by in situ scanning
      transmission X-ray microscopy.
AB  - Phospholipid bilayer coated Si nanowires are one-dimensional (1D) composites that
      provide versatile bio-nanoelectronic functionality via incorporation of a wide
      variety of biomolecules into the phospholipid matrix. The physiochemical
      behaviour of the phospholipid bilayer is strongly dependent on its structure and,
      as a consequence, substantial modelling and experimental efforts have been
      directed at the structural characterization of supported bilayers and unsupported
      phospholipid vesicles; nonetheless, the experimental studies conducted to date
      have exclusively involved volume-averaged techniques, which do not allow for the
      assignment of spatially resolved structural variations that could critically
      impact the performance of the 1D phospholipid-Si NW composites. In this
      manuscript, we use scanning transmission X-ray microscopy (STXM) to probe bond
      orientation and bilayer thickness as a function of position with a spatial
      resolution of ~30 nm for Delta9-cis 1,2-dioleoyl-sn-glycero-3-phosphocholine
      layers prepared Si NWs. When coupled with small angle X-ray scattering
      measurements, the STXM data reveal structural motifs of the Si NWs that give rise
      to multi-bilayer formation and enable assignment of the orientation of specific
      bonds known to affect the order and rigidity of phospholipid bilayers. 

PMID- 25874681
TI  - Quantitative Analysis of Carbon Flow into Photosynthetic Products Functioning as
      Carbon Storage in the Marine Coccolithophore, Emiliania huxleyi.
AB  - The bloom-forming coccolithophore Emiliania huxleyi (Haptophyta) is a dominant
      marine phytoplankton, cells of which are covered with calcareous plates
      (coccoliths). E. huxleyi produces unique lipids of C37-C40 long-chain ketones
      (alkenones) with two to four trans-unsaturated bonds, beta-glucan (but not alpha
      glucan) and acid polysaccharide (AP) associated with the morphogenesis of CaCO3
      crystals in coccoliths. Despite such unique features, there is no detailed
      information on the patterns of carbon allocation into these compounds. Therefore,
      we performed quantitative estimation of carbon flow into various macromolecular
      products by conducting (14)C-radiotracer experiments using NaH(14)CO3 as a
      substrate. Photosynthetic (14)C incorporation into low molecular-mass compounds
      (LMC), extracellular AP, alkenones, and total lipids except alkenones was
      estimated to be 35, 13, 17, and 25 % of total (14)C fixation in logarithmic
      growth phase cells and 33, 19, 18, and 18 % in stationary growth phase cells,
      respectively. However, less than 1 % of (14)C was incorporated into beta-glucan
      in both cells. (14)C-mannitol occupied ca. 5 % of total fixed (14)C as the most
      dominant LMC product. Levels of all (14)C compounds decreased in the dark.
      Therefore, alkenones and LMC (including mannitol), but not beta-glucan, function
      in carbon/energy storage in E. huxleyi, irrespective of the growth phase.
      Compared with other algae, the low carbon flux into beta-glucan is a unique
      feature of carbon metabolism in E. huxelyi.

PMID- 25874682
TI  - Functioning and disability analysis of patients with traumatic brain injury and
      spinal cord injury by using the world health organization disability assessment
      schedule 2.0.
AB  - The purpose of this study is to compare traumatic brain injuries (TBI) and spinal
      cord injuries (SCI) patients' function and disability by using the World Health
      Organization Disability Assessment Schedule 2.0 (WHODAS 2.0); and to clarify the
      factors that contribute to disability. We analyzed data available between
      September 2012 and August 2013 from Taiwan's national disability registry which
      is based on the International Classification of Functioning, Disability, and
      Health (ICF) framework. Of the 2664 cases selected for the study, 1316 pertained
      to TBI and 1348 to SCI. A larger percentage of patients with TBI compared with
      those with SCI exhibited poor cognition, self-care, relationships, life
      activities, and participation in society (all p < 0.001). Age, sex, injury type,
      socioeconomic status, place of residence, and severity of impairment were
      determined as factors that independently contribute to disability (all p < 0.05).
      The WHODAS 2.0 is a generic assessment instrument which is appropriate for
      assessing the complex and multifaceted disability associated with TBI and SCI.
      Further studies are needed to validate the WHODAS 2.0 for TBI and SCI from a
      multidisciplinary perspective. 

PMID- 25874683
TI  - Temporal variations in physico-chemical and microbiological characteristics of
      Mvudi river, South Africa.
AB  - Surface water has been a source of domestic water due to shortage of potable
      water in most rural areas. This study was carried out to evaluate the level of
      contamination of Mvudi River in South Africa by measuring turbidity, electrical
      conductivity (EC), pH, concentrations of nitrate, fluoride, chloride, and
      sulphate. E. coli and Enterococci were analysed using membrane filtration
      technique. Average pH, EC and Turbidity values were in the range of 7.2-7.7, 10.5
      16.1 mS/m and 1.3-437.5 NTU, respectively. The mean concentrations of fluoride,
      chloride, nitrate and sulphate for both the wet and the dry seasons were 0.11
      mg/L and 0.27 mg/L, 9.35 mg/L and 14.82 mg/L, 3.25 mg/L and 6.87 mg/L, 3.24 mg/L
      and 0.70 mg/L, respectively. E. coli and Enterococci counts for both the wet and
      the dry seasons were 4.81 * 103 (log = 3.68) and 5.22 * 103 (log = 3.72), 3.4 *
      103 (log = 3.53) and 1.22 * 103 (log = 3.09), per 100 mL of water, respectively.
      The count of E. coli for both seasons did not vary significantly (p > 0.05) but
      Enterococci count varied significantly (p < 0.001). All the physico-chemical
      parameters obtained were within the recommended guidelines of the Department of
      Water Affairs and Forestry of South Africa and the World Health Organization for
      domestic and recreational water use for both seasons except turbidity and
      nitrates. The microbiological parameters exceeded the established guidelines.
      Mvudi River is contaminated with faecal organisms and should not be used for
      domestic purposes without proper treatment so as to mitigate the threat it poses
      to public health. 

PMID- 25874684
TI  - Combined effects of nonylphenol and bisphenol a on the human prostate epithelial
      cell line RWPE-1.
AB  - The xenoestrogens nonylphenol (NP) and bisphenol A (BPA) are regarded as
      endocrine disrupting chemicals (EDCs) which have widespread occurrence in our
      daily life. In the present study, the purpose was to analyze the combined effects
      of NP and BPA on the human prostate epithelial cell line RWPE-1 using two
      mathematical models based on the Loewe additivity (LA) theory and the Bliss
      independence (BI) theory. RWPE-1 cells were treated with NP (0.01-100 uM) and BPA
      (1-5000 uM) in either a single or a combined format. A cell viability assay and
      lactate dehydrogenase (LDH) leakage rate assay were employed as endpoints. As
      predicted by the two models and based on the cell viability assay, significant
      synergism between NP and BPA were observed. However, based on the LDH assay, the
      trends were reversed. Given that environmental contaminants are frequently
      encountered simultaneously, these data indicated that there were potential
      interactions between NP and BPA, and the combined effects of the chemical mixture
      might be stronger than the additive values of individual chemicals combined,
      which should be taken into consideration for the risk assessment of EDCs. 

PMID- 25874685
TI  - CHRNA3 rs6495308 genotype as an effect modifier of the association between daily
      cigarette consumption and hypertension in Chinese male smokers.
AB  - Cigarette smoking is an important risk factor for hypertension. However, the
      effects on hypertension of the interaction between smoking and the genotype of
      the nicotinic acetylcholine receptor gene are unclear. The purpose of this study
      is to determine whether the CHRNA3 rs6495308 genotype affects the association
      between daily cigarette consumption and hypertension. We recruited 947 male
      smokers in southern China and used a questionnaire administered in face to face
      interviews to obtain information on their socio-demographic characteristics and
      smoking behavior. Blood samples were collected to test for CHRNA3 rs6495308
      genotype variations. Three blood-pressure measurements were taken for each
      participant, and the average values recorded. We found that, compared with light
      smoking (<15 cigarettes per day), heavy smoking (>=15 cigarettes per day) yielded
      a greater risk of hypertension. We also observed that the interaction between
      daily cigarette consumption and the CHRNA3 rs6495308 genotype may affect
      hypertension. Heavy smokers with the homozygous mutant CHRNA3 rs6495308 genotype
      exhibited a significantly greater risk of hypertension than light smokers with
      wild-type CHRNA3 rs6495308 genotypes. The positive interaction between heavy
      smoking and the homozygous mutant CHRNA3 rs6495308 genotype was found to affect
      the likelihood of hypertension in Chinese male smokers. 

PMID- 25874686
TI  - Incorporation of spatial interactions in location networks to identify critical
      geo-referenced routes for assessing disease control measures on a large-scale
      campus.
AB  - Respiratory diseases mainly spread through interpersonal contact. Class
      suspension is the most direct strategy to prevent the spread of disease through
      elementary or secondary schools by blocking the contact network. However, as
      university students usually attend courses in different buildings, the daily
      contact patterns on a university campus are complicated, and once disease
      clusters have occurred, suspending classes is far from an efficient strategy to
      control disease spread. The purpose of this study is to propose a methodological
      framework for generating campus location networks from a routine administration
      database, analyzing the community structure of the network, and identifying the
      critical links and nodes for blocking respiratory disease transmission. The data
      comes from the student enrollment records of a major comprehensive university in
      Taiwan. We combined the social network analysis and spatial interaction model to
      establish a geo-referenced community structure among the classroom buildings. We
      also identified the critical links among the communities that were acting as
      contact bridges and explored the changes in the location network after the
      sequential removal of the high-risk buildings. Instead of conducting a
      questionnaire survey, the study established a standard procedure for constructing
      a location network on a large-scale campus from a routine curriculum database. We
      also present how a location network structure at a campus could function to
      target the high-risk buildings as the bridges connecting communities for blocking
      disease transmission. 

PMID- 25874687
TI  - Flap adhesion and effect on postoperative complication rates using Tissuglu(r) in
      mastectomy patients.
AB  - INTRODUCTION: Post-mastectomy seroma and related complications are common
      problems in modern oncological surgery. Occurrence rates of up to 59% have been
      reported in literature. High-risk patients, that is, those who have undergone
      previous surgeries, present with a high body mass index, have had radiation or
      chemotherapy, present a particular challenge. Noninvasive measures such as fibrin
      based sealants have thus far not been able to effectively reduce complications
      associated with fluid accumulation. A recent study using a lysine-derived
      urethane adhesive named TissuGlu(r) however, showed promising results in patients
      after abdominoplasty. METHODS: 32 consecutively recruited patients received a
      mastectomy using a gold standard mastectomy technique as well as TissuGlu(r) flap
      fixation. A control group of 173 patients, having received a gold standard
      mastectomy-only, was analyzed retrospectively, totaling 205 patients. Primary
      endpoints were post-discharge seroma formation and revision surgery/re
      hospitalization. Secondary endpoints were initial seroma volume, postoperative
      pain, hematoma formation and day of drain removal. RESULTS: No significant
      difference in seroma formation was demonstrated. The revision surgery/re
      hospitalization rate was reduced from 6.9 to 0%, though this did not reach
      significance. Significant improvement could be shown in the TissuGlu(r) group
      regarding time to drain removal (17% decrease), and hematoma formation (14%
      decrease). No difference was shown in postoperative pain. CONCLUSION: Although
      patient numbers are still small, advantages in revision surgery/re
      hospitalization rate, hematoma formation as well as time to drain removal was
      shown for the TissuGlu(r) group. CLINICAL QUESTION/LEVEL OF EVIDENCE:
      Therapeutic, IV.

PMID- 25874688
TI  - Gene expression-based prognostic and predictive tools in breast cancer.
AB  - Genomic assays measuring the expression of multiple genes have made their way
      into clinical practice and their utilization is now recommended by major
      international guidelines. A basic property of these tests is their capability to
      sub-divide patients into high- and low-risk cohorts thereby providing prognostic,
      and in certain settings, predictive decision support. Here, we summarize
      commercially available assays for breast cancer including RT-PCR and gene chip
      based tests. Given the relative uncertainty in cancer treatment, multigene tests
      have the potential for a significant cost reduction as they can pinpoint those
      patients for whom chemotherapy proves to be unnecessary. However, concordance of
      risk assessment for an individual patient is still far from optimal.
      Additionally, emerging multigene approaches focus on predicting therapy response,
      which is a black spot of current tests. Promising techniques include the
      homologous recombination deficiency score, utilization of massive parallel
      sequencing to identify driver genes, employment of internet-based meta-analysis
      tools and investigation of miRNA expression signatures. Combination of multiple
      simultaneous analyses at diagnosis, including classical histopathological
      diagnostics, monogenic markers, genomic signatures and clinical parameters will
      most likely bring maximal benefit for patients. As the main driving force behind
      such genomic tests is the power to achieve cost reduction due to avoiding
      unnecessary systemic treatment, the future is most likely to hold a further
      proliferation of such assays. 

PMID- 25874689
TI  - The characterization of modified starch branching enzymes: toward the control of
      starch chain-length distributions.
AB  - Starch is a complex branched glucose polymer whose branch molecular weight
      distribution (the chain-length distribution, CLD) influences nutritionally
      important properties such as digestion rate. Chain-stopping in starch
      biosynthesis is by starch branching enzyme (SBE). Site-directed mutagenesis was
      used to modify SBEIIa from Zea mays (mSBEIIa) to produce mutants, each differing
      in a single conserved amino-acid residue. Products at different times from in
      vitro branching were debranched and the time evolution of the CLD measured by
      size-exclusion chromatography. The results confirm that Tyr352, Glu513, and
      Ser349 are important for mSBEIIa activity while Arg456 is important for
      determining the position at which the linear glucan is cut. The mutant mSBEIIa
      enzymes have different activities and suggest the length of the transferred chain
      can be varied by mutation. The work shows analysis of the molecular weight
      distribution can yield information regarding the enzyme branching sites useful
      for development of plants yielding starch with improved functionality. 

PMID- 25874690
TI  - Assessment of renal function in patients with unilateral ureteral obstruction
      using whole-organ perfusion imaging with 320-detector row computed tomography.
AB  - BACKGROUND: Obstructed nephropathy is a common complication of several disease
      processes. Accurate evaluation of the functional status of the obstructed kidney
      is important to achieve a good outcome. The purpose of this study was to
      investigate renal cortical and medullary perfusion changes associated with
      unilateral ureteral obstruction (UUO) using whole-organ perfusion imaging with
      320-detector row computed tomography (CT). METHODOLOGY/PRINCIPLE FINDINGS: Sixty
      four patients with UUO underwent whole-organ CT perfusion imaging. Patients were
      divided into 3 groups, mild, moderate, and severe, based on hydronephrosis
      severity. Twenty sex- and age-matched patients without renal disease, who
      referred to abdominal CT, were chosen as control subjects. Mean cortical and
      medullary perfusion parameters of obstructed and contralateral kidneys were
      compared, and mean perfusion ratios between obstructed and contralateral kidneys
      were calculated and compared. Mean cortical or medullary blood flow (BF) and
      blood volume (BV) of the obstructed kidneys in the moderate UUO and BF, BV, and
      clearance (CL) in the severe UUO were significantly lower than those of the
      contralateral kidneys (p < 0.05). The mean cortical or medullary BF of the
      obstructed kidney in the moderate UUO, and BF, BV, and CL in the severe UUO were
      significantly lower than those of the kidneys in control subjects (p < 0.05).
      Mean cortical or medullary BF of the non-obstructed kidneys in the severe UUO
      were statistically greater than that of normal kidneys in control subjects (p <
      0.05). An inverse correlation was observed between cortical and medullary
      perfusion ratios and grades of hydronephosis (p < 0.01).
      CONCLUSIONS/SIGNIFICANCE: Perfusion measurements of the whole kidney can be
      obtained with 320-detector row CT, and estimated perfusion ratios have potential
      for quantitatively evaluating UUO renal injury grades.

PMID- 25874691
TI  - Use of Mycobacterium smegmatis deficient in ADP-ribosyltransferase as surrogate
      for Mycobacterium tuberculosis in drug testing and mutation analysis.
AB  - Rifampicin (Rif) is a first line drug used for tuberculosis treatment. However,
      the emergence of drug resistant strains has necessitated synthesis and testing of
      newer analogs of Rif. Mycobacterium smegmatis is often used as a surrogate for M.
      tuberculosis. However, the presence of an ADP ribosyltransferase (Arr) in M.
      smegmatis inactivates Rif, rendering it impractical for screening of Rif analogs
      or other compounds when used in conjunction with them (Rif/Rif analogs).
      Rifampicin is also used in studying the role of various DNA repair enzymes by
      analyzing mutations in RpoB (a subunit of RNA polymerase) causing Rif resistance.
      These analyses use high concentrations of Rif when M. smegmatis is used as model.
      Here, we have generated M. smegmatis strains by deleting arr (Deltaarr). The M.
      smegmatis Deltaarr strains show minimum inhibitory concentration (MIC) for Rif
      which is similar to that for M. tuberculosis. The MICs for isoniazid,
      pyrazinamide, ethambutol, ciprofloxacin and streptomycin were essentially
      unaltered for M. smegmatis Deltaarr. The growth profiles and mutation spectrum of
      Deltaarr and, Deltaarr combined with DeltaudgB (udgB encodes a DNA repair enzyme
      that excises uracil) strains were similar to their counterparts wild-type for
      arr. However, the mutation spectrum of DeltafpgDeltaarr strain differed somewhat
      from that of the Deltafpg strain (fpg encodes a DNA repair enzyme that excises 8
      oxo-G). Our studies suggest M. smegmatis Deltaarr strain as an ideal model system
      in drug testing and mutation spectrum determination in DNA repair studies. 

PMID- 25874694
TI  - What are the main drivers of the Bitcoin price? Evidence from wavelet coherence
      analysis.
AB  - The Bitcoin has emerged as a fascinating phenomenon in the Financial markets.
      Without any central authority issuing the currency, the Bitcoin has been
      associated with controversy ever since its popularity, accompanied by increased
      public interest, reached high levels. Here, we contribute to the discussion by
      examining the potential drivers of Bitcoin prices, ranging from fundamental
      sources to speculative and technical ones, and we further study the potential
      influence of the Chinese market. The evolution of relationships is examined in
      both time and frequency domains utilizing the continuous wavelets framework, so
      that we not only comment on the development of the interconnections in time but
      also distinguish between short-term and long-term connections. We find that the
      Bitcoin forms a unique asset possessing properties of both a standard financial
      asset and a speculative one. 

PMID- 25874693
TI  - A genetic predictive model for canine hip dysplasia: integration of Genome Wide
      Association Study (GWAS) and candidate gene approaches.
AB  - Canine hip dysplasia is one of the most prevalent developmental orthopedic
      diseases in dogs worldwide. Unfortunately, the success of eradication programs
      against this disease based on radiographic diagnosis is low. Adding the use of
      diagnostic genetic tools to the current phenotype-based approach might be
      beneficial. The aim of this study was to develop a genetic prognostic test for
      early diagnosis of hip dysplasia in Labrador Retrievers. To develop our DNA test,
      775 Labrador Retrievers were recruited. For each dog, a blood sample and a
      ventrodorsal hip radiograph were taken. Dogs were divided into two groups
      according to their FCI hip score: control (A/B) and case (D/E). C dogs were not
      included in the sample. Genetic characterization combining a GWAS and a candidate
      gene strategy using SNPs allowed a case-control population association study. A
      mathematical model which included 7 SNPs was developed using logistic regression.
      The model showed a good accuracy (Area under the ROC curve = 0.85) and was
      validated in an independent population of 114 dogs. This prognostic genetic test
      represents a useful tool for choosing the most appropriate therapeutic approach
      once genetic predisposition to hip dysplasia is known. Therefore, it allows a
      more individualized management of the disease. It is also applicable during
      genetic selection processes, since breeders can benefit from the information
      given by this test as soon as a blood sample can be collected, and act
      accordingly. In the authors' opinion, a shift towards genomic screening might
      importantly contribute to reducing canine hip dysplasia in the future. In
      conclusion, based on genetic and radiographic information from Labrador
      Retrievers with hip dysplasia, we developed an accurate predictive genetic test
      for early diagnosis of hip dysplasia in Labrador Retrievers. However, further
      research is warranted in order to evaluate the validity of this genetic test in
      other dog breeds. 

PMID- 25874695
TI  - Electrohydrodynamic drying of carrot slices.
AB  - Carrots have one of the highest levels of carotene, and they are rich in
      vitamins, fiber and minerals. However, since fresh carrots wilt rapidly after
      harvest under inappropriate storage conditions, drying has been used to improve
      their shelf life and retain nutritional quality. Therefore, to further
      investigate the potential of this method, carrot slices were dried in an EHD
      system in order to study the effect of different voltages on drying rate. As
      measures of quality, carotene content and rehydration ratio were, respectively,
      compared against the conventional oven drying regime. Carotene, the main
      component of the dried carrot, and rehydration characteristics of the dried
      product can both indicate quality by physical and chemical changes during the
      drying process. Mathematical modeling and simulation of drying curves were also
      performed, using root mean square error, reduced mean square of the deviation and
      modeling efficiency as the primary criteria to select the equation that best
      accounts for the variation in the drying curves of the dried samples.
      Theoretically, the Page model was best suited for describing the drying rate
      curve of carrot slices at 10kV to 30kV. Experimentally, the drying rate of
      carrots was notably greater in the EHD system when compared to control, and
      quality, as determined by carotene content and rehydration ratio, was also
      improved when compared to oven drying. Therefore, this work presents a facile and
      effective strategy for experimentally and theoretically determining the drying
      properties of carrots, and, as a result, it provides deeper insight into the
      industrial potential of the EHD drying technique.

PMID- 25874692
TI  - WIN 55,212-2, agonist of cannabinoid receptors, prevents amyloid beta1-42 effects
      on astrocytes in primary culture.
AB  - Alzheimer's disease (AD), a neurodegenerative illness involving synaptic
      dysfunction with extracellular accumulation of Abeta1-42 toxic peptide, glial
      activation, inflammatory response and oxidative stress, can lead to neuronal
      death. Endogenous cannabinoid system is implicated in physiological and
      physiopathological events in central nervous system (CNS), and changes in this
      system are related to many human diseases, including AD. However, studies on the
      effects of cannabinoids on astrocytes functions are scarce. In primary cultured
      astrocytes we studied cellular viability using MTT assay. Inflammatory and
      oxidative stress mediators were determined by ELISA and Western-blot techniques
      both in the presence and absence of Abeta1-42 peptide. Effects of WIN 55,212-2 (a
      synthetic cannabinoid) on cell viability, inflammatory mediators and oxidative
      stress were also determined. Abeta1-42 diminished astrocytes viability, increased
      TNF-alpha and IL-1beta levels and p-65, COX-2 and iNOS protein expression while
      decreased PPAR-gamma and antioxidant enzyme Cu/Zn SOD. WIN 55,212-2 pretreatment
      prevents all effects elicited by Abeta1-42. Furthermore, cannabinoid WIN 55,212-2
      also increased cell viability and PPAR-gamma expression in control astrocytes. In
      conclusion cannabinoid WIN 55,212-2 increases cell viability and anti
      inflammatory response in cultured astrocytes. Moreover, WIN 55,212-2 increases
      expression of anti-oxidant Cu/Zn SOD and is able to prevent inflammation induced
      by Abeta1-42 in cultured astrocytes. Further studies would be needed to assess
      the possible beneficial effects of cannabinoids in Alzheimer's disease patients.

PMID- 25874696
TI  - Serosurveillance of vaccine preventable diseases and hepatitis C in healthcare
      workers from Lao PDR.
AB  - BACKGROUND AND AIMS: Healthcare workers (HCW) have an increased risk of exposure
      to infectious diseases and are a potential source of infections for their
      patients. The Lao People's Democratic Republic (Lao PDR) has no national policy
      regarding HCW vaccinations and routine vaccination coverage is low within the
      general population. This cross-sectional serostudy determines the level of
      exposure and risk of infection in Lao HCW against 6 vaccine preventable diseases
      and hepatitis C. METHODS: 1128 HCW were recruited from 3 central, 2 provincial
      and 8 district hospitals. Sera were tested by ELISA for the presence of
      antibodies and antigens to hepatitis B, hepatitis C, measles, rubella, varicella
      zoster, tetanus and diphtheria. RESULTS: Only 53.1% of the HCW had protective
      anti-hepatitis B surface antigen antibodies (anti-HBs) with 48.8% having anti
      hepatitis B core antibodies (anti-HBc), indicating previous exposure and 8.0%
      were hepatitis B surface antigen carriers. 3.9% were hepatitis C seropositive.
      Measles and rubella antibodies were detected in 95.4% and 86.2% of the HCW, with
      11.9% of females being unprotected against rubella. Antibodies against varicella
      zoster, tetanus and diphtheria were detected in 95%, 78.8% and 55.3%,
      respectively. Seroprevalence varied according to age, gender and number of
      children. CONCLUSION: An unacceptably high proportion of Lao HCW remain
      susceptible to infection with hepatitis B, diphtheria, tetanus and rubella.
      Furthermore, a high number of healthcare workers are chronically infected with
      hepatitis B and C viruses. These data emphasize the need for a robust HCW
      vaccination policy in addition to increased awareness within this subpopulation.

PMID- 25874697
TI  - Diurnal temperature variations affect development of a herbivorous arthropod pest
      and its predators.
AB  - The impact of daily temperature variations on arthropod life history remains
      woefully understudied compared to the large body of research that has been
      carried out on the effects of constant temperatures. However, diurnal varying
      temperature regimes more commonly represent the environment in which most
      organisms thrive. Such varying temperature regimes have been demonstrated to
      substantially affect development and reproduction of ectothermic organisms,
      generally in accordance with Jensen's inequality. In the present study we
      evaluated the impact of temperature alternations at 4 amplitudes (DTR0, +5, +10
      and +15 degrees C) on the developmental rate of the predatory mites Phytoseiulus
      persimilis Athias-Henriot and Neoseiulus californicus McGregor (Acari:
      Phytoseiidae) and their natural prey, the two-spotted spider mite Tetranychus
      urticae Koch (Acari: Tetranychidae). We have modelled their developmental rates
      as a function of temperature using both linear and nonlinear models. Diurnally
      alternating temperatures resulted in a faster development in the lower
      temperature range as compared to their corresponding mean constant temperatures,
      whereas the opposite was observed in the higher temperature range. Our results
      indicate that Jensen's inequality does not suffice to fully explain the
      differences in developmental rates at constant and alternating temperatures,
      suggesting additional physiological responses play a role. It is concluded that
      diurnal temperature range should not be ignored and should be incorporated in
      predictive models on the phenology of arthropod pests and their natural enemies
      and their performance in biological control programmes. 

PMID- 25874699
TI  - Surgical management for early-stage bilateral breast cancer patients in China.
AB  - BACKGROUND: The aim of this study was to investigate the current surgical
      management strategy for bilateral breast cancer (BBC) patients and to assess the
      changes in this strategy in China. METHODS: This is a retrospective review of all
      patients with early-stage BBC who underwent surgical treatment at the Fudan
      University Shanghai Cancer Center between June 2007 and June 2014. RESULTS: A
      total of 15,337 patients with primary breast cancer were identified. Of these
      patients, 218 (1.5%) suffered from synchronous bilateral breast cancer (sBBC),
      and 296 (2.0%) suffered from metachronous bilateral breast cancer (mBBC).
      Patients with a lobular carcinoma component, those with estrogen receptor
      positive cancer, and those with an accompanying sclerosing adenosis in the
      affected breast tended to develop BBC. The rates of bilateral mastectomy, breast
      conserving therapy, reconstruction, and combined surgeries were 86.2%, 6.4%,
      3.7%, and 3.7%, respectively, for patients with sBBC and 81.1%, 4.4%, 3.0%, and
      11.5%, respectively, for patients with mBBC. The interval between bilateral
      cancers, age at first diagnosis of breast cancer, histopathological type, and
      stage have significant impacts on the choice of surgery for patients with BBC.
      CONCLUSIONS: Bilateral mastectomy was the dominant surgical management for
      patients with BBC in China, despite the increased application of breast
      reconstruction surgery observed in recent years. Bilateral prosthetic breast
      reconstruction was the ideal choice for patients with sBBC. Chinese surgeons
      should take responsibility for patient education and inform their patients about
      their surgical options.

PMID- 25874700
TI  - General relationship of global topology, local dynamics, and directionality in
      large-scale brain networks.
AB  - The balance of global integration and functional specialization is a critical
      feature of efficient brain networks, but the relationship of global topology,
      local node dynamics and information flow across networks has yet to be
      identified. One critical step in elucidating this relationship is the
      identification of governing principles underlying the directionality of
      interactions between nodes. Here, we demonstrate such principles through
      analytical solutions based on the phase lead/lag relationships of general
      oscillator models in networks. We confirm analytical results with computational
      simulations using general model networks and anatomical brain networks, as well
      as high-density electroencephalography collected from humans in the conscious and
      anesthetized states. Analytical, computational, and empirical results demonstrate
      that network nodes with more connections (i.e., higher degrees) have larger
      amplitudes and are directional targets (phase lag) rather than sources (phase
      lead). The relationship of node degree and directionality therefore appears to be
      a fundamental property of networks, with direct applicability to brain function.
      These results provide a foundation for a principled understanding of information
      transfer across networks and also demonstrate that changes in directionality
      patterns across states of human consciousness are driven by alterations of brain
      network topology. 

PMID- 25874701
TI  - Influence of ecological factors on the production of active substances in the
      anti-cancer plant Sinopodophyllum hexandrum (Royle) T.S. Ying.
AB  - The quality of traditional Chinese herbal medicine, which plays a very important
      role in the health system of China, is determined by the active substances
      produced by the plants. The type, content, and proportion of these substances may
      vary depending on ecological factors in areas where the plants are grown.
      Sinopodophyllum hexandrum (Royle) T.S. Ying, an endangered plant species with
      great medical value, was investigated in eight production locations
      representative of its natural geographical distribution range in China. The
      correlation between the contents of the active ingredients extracted from the
      roots and rhizomes of S. hexandrum and the ecological factors were evaluated step
      by-step using a series of computational biology methodologies. The results showed
      that ecological factors had significant effects on the contents but not on the
      types of the active ingredients in eight production locations. The primary
      ecological factors influencing the active substances included the annual average
      precipitation, July mean temperature, frost-free period, sunshine duration, soil
      pH, soil organic matter, and rapidly available potassium in the soil. The annual
      average precipitation was the most important determinant factor and was
      significantly and negatively correlated with the active ingredient contents (P <
      0.001). In contrast, organic matter was the most important limiting factor and
      was significantly and positively correlated with the active substances. These
      ecological factors caused 98.13% of the total geographical variation of the
      active ingredient contents. The climate factors contributed more to the active
      ingredient contents than did the soil factors. It was concluded that from the
      view of the contents of the secondary metabolites and ecological factors of each
      growing location, in Jingyuan, Ningxia Province, and Yongdeng, Gansu Province,
      conditions were favorable to the production of podophyllotoxin and lignans,
      whereas in Shangri-La, Yunnan Province, and Nyingchi, Tibet, conditions were
      favorable to the production of quercetin and kaempferol. 

PMID- 25874703
TI  - Correction: Behavioral and electrophysiological characterization of Dyt1
      heterozygous knockout mice.

PMID- 25874704
TI  - The incidence of pressure ulcers in surgical patients of the last 5 years: a
      systematic review.
AB  - This systematic review looks at the incidence of pressure ulcers in surgical
      patients of the last 5 years. METHODS: The authors searched Pubmed and Web of
      Science for studies published after 2005. Screen- ing and data abstraction were
      performed independently by 2 reviewers. RESULTS: Seventeen studies (5,451
      patients) met the inclusion criteria. The incidence of surgery-related pressure
      ulcers ranged from 0.003 to 0.574. The pooled incidence was 0.15 (95% CI 0.14
      0.16, I2 = 98.2%). For cardiac surgery, hip fracture surgery, and patients on the
      surgical intensive care unit, the pooled incidence was 0.18 (95% CI 0.14-0.22, I2
      = 62.8%), 0.22 (95% CI 0.20-0.24, I2= 98.4%), and 0.11 (95% CI 0.09-0.13, I2 =
      98.5%), respectively. CONCLUSION: The data on the incidence of surgery-related
      pressure ulcers indicates that appropriate monitoring and treatment need to be
      performed.

PMID- 25874702
TI  - Association between microalbuminuria predicting in-stent restenosis after
      myocardial infarction and cellular senescence of endothelial progenitor cells.
AB  - OBJECTIVE: Relationship between microalbuminuria and worse outcome of coronary
      artery disease patients is discussed, but its underlying pathophysiological
      mechanism remains unclear. We investigated the role of microalbuminuria to the
      function of endothelial progenitor cells (EPCs), that might affect to outcome of
      acute myocardial infarction (AMI) patients. METHODS: Forty-five AMI patients were
      divided into two groups according to their urinary albumin excretion: normal (n =
      24) and microalbuminuria (>30 mg/day, n = 21). At day-2 and day-7 after AMI
      onset, circulating-EPCs (CD34+ Flk1+) were quantified by flow cytometry. The
      number of lectin-acLDL-positive cultured-EPCs immobilized on fibronectin was
      determined. To assess the cellular senescence of cultured-EPCs, the expression
      level of sirtuin-1 mRNA and the number of SA-beta-gal positive cell were
      evaluated. Angiographic late in-stent loss after percutaneous coronary
      intervention (PCI) was evaluated at a six-month follow-up. RESULTS: No
      significant differences in coronary risk and the extent of myocardial damage were
      observed between the two groups. Late in-stent loss at the six-month follow-up
      was significantly higher in the microalbuminuria group (normal:microalbuminuria =
      0.76+/-0.34:1.18+/-0.57 mm, p=0.021). The number of circulating-EPCs was
      significantly increased in microalbuminuria group at day-7, however, improved
      adhesion of EPCs was observed in normal group but not in microalbuminuria group
      from baseline to day-7 (+3.1+/-8.3:-1.3+/-4.4%: p<0.05). On the other hand, in
      microalbuminuria group at day-7, the level of sirtuin-1 mRNA expression of
      cultured-EPCs was significantly decreased (7.1+/-8.9:2.5+/-3.7 fold, p<0.05),
      which was based on the negative correlation between the level of sirtuin-1 mRNA
      expression and the extent of microalbuminuria. The ratio of SA-beta-gal-positive
      cells in microalbuminuria group was increased compared to that of normal group.
      CONCLUSIONS: Microalbuminuria in AMI patients is closely associated with
      functional disorder of EPCs via cellular senescence, that predicts the
      aggravation of coronary remodeling after PCI.

PMID- 25874698
TI  - Frequency and characteristics of familial melanoma in Spain: the FAM-GEM-1 Study.
AB  - INTRODUCTION: Familial history of melanoma is a well-known risk factor for the
      disease, and 7% melanoma patients were reported to have a family history of
      melanoma. Data relating to the frequency and clinical and pathological
      characteristics of both familial and non-familial melanoma in Spain have been
      published, but these only include patients from specific areas of Spain and do
      not represent the data for the whole of Spain. PATIENTS AND METHODS: An
      observational study conducted by the Spanish Group of Melanoma (GEM) analyzed the
      family history of patients diagnosed with melanoma between 2011 and 2013 in the
      dermatology and oncology departments. RESULTS: In all, 1047 patients were
      analyzed, and 69 (6.6%) fulfilled criteria for classical familial melanoma (two
      or more first-degree relatives diagnosed with melanoma). Taking into account
      other risk factors for familial melanoma, such as multiple melanoma, pancreatic
      cancer in the family or second-degree relatives with melanoma, the number of
      patients fulfilling the criteria increased to 165 (15.8%). Using a univariate
      analysis, we determined that a Breslow index of less than 1 mm, negative mitosis,
      multiple melanoma, and a history of sunburns in childhood were more frequent in
      familial melanoma patients, but a multivariate analysis revealed no differences
      in any pathological or clinical factor between the two groups. CONCLUSIONS:
      Similar to that observed in other countries, familial melanoma accounts for 6.6%
      of melanoma diagnoses in Spain. Although no differences in the multivariate
      analysis were found, some better prognosis factors, such as Breslow index, seem
      more frequent in familial melanoma, which reflect a better early detection marker
      and/or a different biological behavior.

PMID- 25874705
TI  - [Not Available].
AB  - An important part of the wound healing process is the removal of necrotic tissue
      from a wound to promote healing. Enzymatic de- bridement is one of the widely
      used methods to accomplish this goal. Clostridium collagenase (C. collagenase)
      containing ointment is fre- quently used in clinics to debride wounds. In this
      work, the influence of metal salts and various types of surfactants on the
      enzymatic activ- ity of C. collagenase is tested. The relationship between charge
      and size of metal ions and surfactant structure is explained in the context of
      enzyme inhibition. Commonly used wound care products, such as cleansers,
      dressings, antimicrobial formulations, and silver dressings are tested with C.
      collagenase. The results are discussed in terms of enzyme compatibility with such
      materials, and recommendations for use of wound care accessories in conjunction
      with the debriding en- zyme are given, with the aim to help wound care providers
      make more educated choices towards accomplishing optimal therapy outcome.    . 

PMID- 25874706
TI  - Effects of Locally and Systemically Applied n-3 Fatty Acid on Oral Ulcer Recovery
      Process in Rats.
AB  - Introduction. Ulcers are one of the most frequent diseases af- fecting the oral
      cavity. The aim of this study was to assess the effects of omega-3 fatty acid
      (topical and systemic) on oral mucosa wound healing in rats. METHODS AND
      MATERIALS: In this study, adult male rats in 5 groups (n = 16 per group) were
      used (L: local, S: systemic, LB: local blank, SB: systemic blank, and C:
      control.) A wound (2 mm di- ameter) was punched into the hard palate of each rat.
      A mucosal de- fect (2 mm in diameter and 0.2 mm in wall thickness) was made to
      the depth of the periosteum in the palate with a round stainless steel blade
      designed for punch biopsy. For topical application, a swab was soaked in L omega
      3 or LB and packed into the wound. For systemic treatment, 2 cc of the S omega-3
      acid or SB was guided into the stom- ach by gastric gavage. The control group was
      not treated. Histological samples were harvested on post-injury days 2, 4, 6, and
      8. RESULTS: The highest amount of polymorphonuclear (PMN) cells was observed on
      days 2 and 4 in the LB group. The control group had the highest inflammation
      score on days 2 and 4, and the lowest reepithelialization score on days 2, 4, 6,
      and 8. The thickest epithelium was observed in the L and S groups on days 6 and
      8. CONCLUSION: Omega-3 fatty acid (L and S) increases fibroblast counts and
      decreases PMN cell counts. Moreover, this compound causes an increase in
      reepithelialization and epithelial thickness.    .

PMID- 25874707
TI  - Preclinical evaluation of wound treatment with hyaluronan-iodine hydrogel.
AB  - A mixture of hyaluronan and iodine complex KI3 (Hyiodine(r)) has been developed
      to support wound healing. In this study, the effect of hyaluronan, KI3, and their
      combination on progression of wound healing in excision skin wounds in rats was
      determined. METHODS: To evaluate the possible toxic effects of iodine after
      Hyiodine application for wound healing, iodine systemic absorption from the
      Hyiodine-treat- ed wounds and its distribution profile were quantitatively
      described and compared after intravenous iodide administration using 131I as a
      radiolabel. RESULTS: Treatment of rats with Hyiodine resulted in an enhancement
      of wound healing, proved by greater degrees of wound contraction and reduction in
      mean wound healing time compared to other treated rats on hours 1, 2, 24, and
      216. Even if wound therapy with Hyiodine resulted in systemic iodine uptake, the
      estimated iodine absorbed dose in human therapy is tolerable, and the theoretical
      risk of its systemic toxic effects is minimal. CONCLUSION: A hyaluronan-iodine
      hydrogel has a great potential for effective treatment of wounds.  .

PMID- 25874708
TI  - Tap Water has No Influence on Microbial Colonization of Skin Wounds in Rats.
AB  - The aim of this study was to investigate the influence of tap water on microbial
      colonization of skin wounds in rats. METHODS: A cir- cular wound 2.4 cm in
      diameter was created on the back of 40 Wistar rats, which were randomly assigned
      to the control (n = 20) or study (n = 20) group. The wounds were cleansed daily
      using a sterile 0.9% sodium chloride solution (control group) or tap water (study
      group) for 6 days, following a standardized protocol. Sequential samples were
      collected for microbiological analysis every other day. RESULTS: Microbial growth
      occurred in 49% of the samples from the control group and in 47% of the samples
      from the study group (P = 0.39). There was no significant difference in microbial
      growth between groups for the different culture media: thioglycolate (P = 0.20),
      mannitol salt agar (P = 0.53), blood agar (P = 0.61), eosin methylene blue agar
      (P = 0.51), and Sabouraud agar (P = 0.34). The following microorganisms were
      identified: Bacil- lus subtilis, Staphylococcus sp, Aureobasidium sp, Penicillium
      sp, and Cladosporium sp. CONCLUSION: The use of tap water for cleansing skin
      wounds in rats had no effect on microbial colonization compared with the use of a
      sterile saline solution.    .

PMID- 25874710
TI  - Landscape genetics of Schistocephalus solidus parasites in threespine stickleback
      (Gasterosteus aculeatus) from Alaska.
AB  - The nature of gene flow in parasites with complex life cycles is poorly
      understood, particularly when intermediate and definitive hosts have contrasting
      movement potential. We examined whether the fine-scale population genetic
      structure of the diphyllobothriidean cestode Schistocephalus solidus reflects the
      habits of intermediate threespine stickleback hosts or those of its definitive
      hosts, semi-aquatic piscivorous birds, to better understand complex host-parasite
      interactions. Seventeen lakes in the Cook Inlet region of south-central Alaska
      were sampled, including ten in the Matanuska-Susitna Valley, five on the Kenai
      Peninsula, and two in the Bristol Bay drainage. We analyzed sequence variation
      across a 759 bp region of the mitochondrial DNA (mtDNA) cytochrome oxidase I
      region for 1,026 S. solidus individuals sampled from 2009-2012. We also analyzed
      allelic variation at 8 microsatellite loci for 1,243 individuals. Analysis of
      mtDNA haplotype and microsatellite genotype variation recovered evidence of
      significant population genetic structure within S. solidus. Host, location, and
      year were factors in structuring observed genetic variation. Pairwise measures
      revealed significant differentiation among lakes, including a pattern of
      isolation-by-distance. Bayesian analysis identified three distinct genotypic
      clusters in the study region, little admixture within hosts and lakes, and a
      shift in genotype frequencies over time. Evidence of fine-scale population
      structure in S. solidus indicates that movement of its vagile, definitive avian
      hosts has less influence on gene flow than expected based solely on movement
      potential. Observed patterns of genetic variation may reflect genetic drift,
      behaviors of definitive hosts that constrain dispersal, life history of
      intermediate hosts, and adaptive specificity of S. solidus to intermediate host
      genotype. 

PMID- 25874709
TI  - Association of polymorphisms in HLA antigen presentation-related genes with the
      outcomes of HCV infection.
AB  - Antigen-presentation genes play a vital role in the pathogenesis of HCV
      infection. However, the relationship of variants of these genes with spontaneous
      outcomes of HCV infection has not been fully investigated. To explore novel loci
      in the Chinese population, 34 tagging-SNPs in 9 candidate genes were genotyped
      for their associations with the outcomes of HCV infection. The distributions of
      different genotypes and haplotypes were compared among 773 HCV-negative controls,
      246 subjects with HCV natural clearance, and 218 HCV persistent carriers
      recruited from hemodialysis patients and intravenous drug users. Our study
      implicated that TAP2, HLA-DOA, HLA-DOB, and tapasin loci were novel candidate
      regions for susceptibility to HCV infection and viral clearance in the Chinese
      population. Logistic regression analyses showed that TAP2 rs1800454 A (OR = 1.48,
      P = 0.002) and HLA-DOB rs2071469 G (OR = 1.23, P = 0.048) were significantly
      associated with increased susceptibility to establishment of HCV infection.
      However, high-risk behavior exposure and age were stronger predictors of HCV
      infection. Mutation of tapasin rs9277972 T (OR = 1.57, P =0.043) increased the
      risk of HCV chronicity, and HLA-DOA rs3128935 C (OR = 0.62, P = 0.019) increased
      the chance of viral resolution. With regards to the effect of rs3128925,
      interactions were found with high-risk behavior (P = 0.013) and age (P = 0.035).
      The risk effect of rs3128925 T for persistent HCV infection was higher in
      injecting drug users (vs. dialysis patients) and in subjects >= 40 years old (vs.
      < 40 years old). 

PMID- 25874711
TI  - Bistability: requirements on cell-volume, protein diffusion, and thermodynamics.
AB  - Bistability is considered wide-spread among bacteria and eukaryotic cells,
      useful, e.g., for enzyme induction, bet hedging, and epigenetic switching.
      However, this phenomenon has mostly been described with deterministic dynamic or
      well-mixed stochastic models. Here, we map known biological bistable systems onto
      the well-characterized biochemical Schlogl model, using analytical calculations
      and stochastic spatiotemporal simulations. In addition to network architecture
      and strong thermodynamic driving away from equilibrium, we show that bistability
      requires fine-tuning towards small cell volumes (or compartments) and fast
      protein diffusion (well mixing). Bistability is thus fragile and hence may be
      restricted to small bacteria and eukaryotic nuclei, with switching triggered by
      volume changes during the cell cycle. For large volumes, single cells generally
      loose their ability for bistable switching and instead undergo a first-order
      phase transition.

PMID- 25874712
TI  - Parity of indigenous and non-indigenous women in Brazil: does the reported number
      of children born depend upon who answers national census questions?
AB  - Taking parity as the main analytic variable, the objective of this study is to
      investigate whether the patterns of response to national census questions in
      Brazil differ when Indigenous and non-Indigenous women are compared, taking into
      consideration whether the information was provided by the women directly or by a
      proxy respondent (another household member or a non-resident). We use data on
      children ever born to Indigenous and non-Indigenous women from two Brazilian
      regions, the Northeast and the North. Data on the number of household members,
      total household rooms, interviewee's color/race, educational attainment, age,
      parity, and type of respondent were obtained from the 2010 Brazilian census. The
      relation between color/race and reported parity, as well as the impact of the
      type of respondent on this association were assessed with the Zero-inflated
      Negative Binomial regression, stratified by region (North and Northeast) and
      urban/rural status. Just over half of census interviewees answered directly the
      census questions (51.2% in the North and 54.4% in the Northeast). Indigenous
      women in the North region had the highest percentage of interviews carried out
      with a non-resident (12.7% total; 15.0% and 3.0% in rural and urban areas,
      respectively). Regardless of color/race, parity means were considerably higher
      when the question was answered by the woman directly (93.5%-101.4% and 15.6%
      21.7% higher, compared co-resident and non-resident based answers, respectively).
      Parity underreporting was particularly strong in Indigenous women living in the
      rural North (16.0% less in comparison to White women). Proxy respondents tend to
      underestimate the count of children, particularly among Indigenous women from the
      North. The implementation of certain methodological alternatives in the Brazilian
      national censuses, such as the selection and training of census takers to work
      specifically in Indigenous territories, might be a productive means to improve
      data collection. 

PMID- 25874713
TI  - Deletion of FADD in macrophages and granulocytes results in RIP3- and MyD88
      dependent systemic inflammation.
AB  - Myeloid cells, which include monocytes, macrophages, and granulocytes, are
      important innate immune cells, but the mechanism and downstream effect of their
      cell death on the immune system is not completely clear. Necroptosis is an
      alternate form of cell death that can be triggered when death receptor-mediated
      apoptosis is blocked, for example, in stimulated Fas-associated Death Domain
      (FADD) deficient cells. We report here that mice deficient for FADD in myeloid
      cells (mFADD-/-) exhibit systemic inflammation with elevated inflammatory
      cytokines and increased levels of myeloid and B cell populations while their
      dendritic and T cell numbers are normal. These phenotypes were abolished when
      RIP3 deficiency was introduced, suggesting that systemic inflammation is caused
      by RIP3-dependent necroptotic and/or inflammatory activity. We further found that
      loss of MyD88 can rescue the systemic inflammation observed in these mice. These
      phenotypes are surprisingly similar to that of dendritic cell (DC)-specific FADD
      deficient mice with the exception that DC numbers are normal in mFADD-/- mice.
      Together these data support the notion that innate immune cells are constantly
      being stimulated through the MyD88-dependent pathway and aberrations in their
      cell death machinery can result in systemic effects on the immune system. 

PMID- 25874714
TI  - Evaluation of locally established reference intervals for hematology and
      biochemistry parameters in Western Kenya.
AB  - BACKGROUND: Important differences have been demonstrated in laboratory parameters
      from healthy persons in different geographical regions and populations, mostly
      driven by a combination of genetic, demographic, nutritional, and environmental
      factors. Despite this, European and North American derived laboratory reference
      intervals are used in African countries for patient management, clinical trial
      eligibility, and toxicity determination; which can result in misclassification of
      healthy persons as having laboratory abnormalities. METHODS: An observational
      prospective cohort study known as the Kisumu Incidence Cohort Study (KICoS) was
      conducted to estimate the incidence of HIV seroconversion and identify
      determinants of successful recruitment and retention in preparation for an HIV
      vaccine/prevention trial among young adults and adolescents in western Kenya.
      Laboratory values generated from the KICoS were compared to published region
      specific reference intervals and the 2004 NIH DAIDS toxicity tables used for the
      trial. RESULTS: About 1106 participants were screened for the KICoS between
      January 2007 and June 2010. Nine hundred and fifty-three participants aged 16 to
      34 years, HIV-seronegative, clinically healthy, and non-pregnant were selected
      for this analysis. Median and 95% reference intervals were calculated for
      hematological and biochemistry parameters. When compared with both published
      region-specific reference values and the 2004 NIH DAIDS toxicity table, it was
      shown that the use of locally established reference intervals would have resulted
      in fewer participants classified as having abnormal hematological or biochemistry
      values compared to US derived reference intervals from DAIDS (10% classified as
      abnormal by local parameters vs. >40% by US DAIDS). Blood urea nitrogen was most
      often out of range if US based intervals were used: <10% abnormal by local
      intervals compared to >83% by US based reference intervals. CONCLUSION:
      Differences in reference intervals for hematological and biochemical parameters
      between western and African populations highlight importance of developing local
      reference intervals for clinical care and trials in Africa.

PMID- 25874715
TI  - Bacteriological assessment of healthcare-associated pneumonia using a clone
      library analysis.
AB  - BACKGROUND: The causative pathogens of healthcare-associated pneumonia (HCAP)
      remain controversial, and the use of conventional cultivation of sputum samples
      is occasionally inappropriate due to the potential for oral bacterial
      contamination. It is also sometimes difficult to determine whether methicillin
      resistant Staphylococcus aureus (MRSA) is a true causative pathogen of HCAP.
      METHODS: We evaluated the bacterial diversity in bronchoalveolar lavage fluid
      (BALF) using molecular and cultivation methods in 82 HCAP patients. BALF
      specimens were obtained from the lesions of pneumonia using bronchoscopy. The
      bacterial flora was analyzed according to the clone library method using
      amplified fragments of the 16S ribosomal RNA gene with universal primers. In
      addition, sputum cultures and the above specimens were assessed. RESULTS: Eighty
      (97.6%) of the 82 BALF samples obtained from the patients with HCAP showed
      positive polymerase chain reaction results. The predominant phylotypes detected
      in the BALF in this study included bacteria common in cases of community- and
      hospital-acquired pneumonia. In addition, the phylotypes of streptococci and
      anaerobes were detected in 19 (23.2%) and 8 (9.8%) cases, respectively. In
      particular, phylotypes of streptococci were highly detected among the patients 75
      of age or older. Staphylococcus aureus was cultured in 23 (28.0%) cases using
      conventional cultivation methods and detected in only 6 (7.3%) cases as
      predominant phylotypes according to the clone library method. CONCLUSIONS: The
      clone library analysis of BALF in the HCAP patients detected heterogeneous
      bacteria and a high incidence of streptococci compared with that observed using
      cultivation methods. In addition, the results of our study may indicate a lower
      incidence of MRSA than previously expected in HCAP patients.

PMID- 25874716
TI  - Statistical properties and pre-hit dynamics of price limit hits in the Chinese
      stock markets.
AB  - Price limit trading rules are adopted in some stock markets (especially emerging
      markets) trying to cool off traders' short-term trading mania on individual
      stocks and increase market efficiency. Under such a microstructure, stocks may
      hit their up-limits and down-limits from time to time. However, the behaviors of
      price limit hits are not well studied partially due to the fact that main stock
      markets such as the US markets and most European markets do not set price limits.
      Here, we perform detailed analyses of the high-frequency data of all A-share
      common stocks traded on the Shanghai Stock Exchange and the Shenzhen Stock
      Exchange from 2000 to 2011 to investigate the statistical properties of price
      limit hits and the dynamical evolution of several important financial variables
      before stock price hits its limits. We compare the properties of up-limit hits
      and down-limit hits. We also divide the whole period into three bullish periods
      and three bearish periods to unveil possible differences during bullish and
      bearish market states. To uncover the impacts of stock capitalization on price
      limit hits, we partition all stocks into six portfolios according to their
      capitalizations on different trading days. We find that the price limit trading
      rule has a cooling-off effect (object to the magnet effect), indicating that the
      rule takes effect in the Chinese stock markets. We find that price continuation
      is much more likely to occur than price reversal on the next trading day after a
      limit-hitting day, especially for down-limit hits, which has potential practical
      values for market practitioners. 

PMID- 25874717
TI  - Endothelial-derived oxidative stress drives myofibroblastic activation and
      calcification of the aortic valve.
AB  - AIMS: Oxidative stress is present in and contributes to calcification of the
      aortic valve, but the driving factors behind the initiation of valve oxidative
      stress are not well understood. We tested whether the valve endothelium acts as
      an initiator and propagator of oxidative stress in aortic valve disease. METHODS
      AND RESULTS: Calcified human aortic valves showed side-specific elevation of
      superoxide in the endothelium, co-localized with high VCAM1 expression, linking
      oxidative stress, inflammation, and valve degeneration. Treatment with
      inflammatory cytokine TNFalpha increased superoxide and oxidative stress and
      decreased eNOS and VE-cadherin acutely over 48 hours in aortic valve endothelial
      cells (VEC) and chronically over 21 days in ex vivo AV leaflets. Co-treatment of
      VEC with tetrahydrobiopterin (BH4) but not apocynin mitigated TNFalpha-driven VEC
      oxidative stress. Co-treatment of ex vivo AV leaflets with TNFalpha+BH4 or
      TNFalpha+peg-SOD rescued endothelial function and mitigated inflammatory
      responses. Both BH4 and peg-SOD rescued valve leaflets from the pro-osteogenic
      effects of TNFalpha treatment, but only peg-SOD was able to mitigate the
      fibrogenic effects, including increased collagen and alphaSMA expression.
      CONCLUSIONS: Aortic valve endothelial cells are a novel source of oxidative
      stress in aortic valve disease. TNFalpha-driven VEC oxidative stress causes loss
      of endothelial protective function, chronic inflammation, and fibrogenic and
      osteogenic activation, mitigated differentially by BH4 and peg-SOD. These
      mechanisms identify new targets for tailored antioxidant therapy focused on
      mitigation of oxidative stress and restoration of endothelial protection.

PMID- 25874718
TI  - Impacts and recovery from severe tropical cyclone Yasi on the Great Barrier Reef.
AB  - Full recovery of coral reefs from tropical cyclone (TC) damage can take decades,
      making cyclones a major driver of habitat condition where they occur regularly.
      Since 1985, 44 TCs generated gale force winds (>=17 metres/second) within the
      Great Barrier Reef Marine Park (GBRMP). Of the hurricane strength TCs (>=H1
      Saffir Simpson scale; >= category 3 Australian scale), TC Yasi (February, 2011)
      was the largest. In the weeks after TC Yasi crossed the GBRMP, participating
      researchers, managers and rangers assessed the extent and severity of reef damage
      via 841 Reef Health and Impact Surveys at 70 reefs. Records were scaled into five
      damage levels representing increasingly widespread colony-level damage (1, 2, 3)
      and reef structural damage (4, 5). Average damage severity was significantly
      affected by direction (north vs south of the cyclone track), reef shelf position
      (mid-shelf vs outer-shelf) and habitat type. More outer-shelf reefs suffered
      structural damage than mid-shelf reefs within 150 km of the track. Structural
      damage spanned a greater latitudinal range for mid-shelf reefs than outer-shelf
      reefs (400 vs 300 km). Structural damage was patchily distributed at all
      distances, but more so as distance from the track increased. Damage extended much
      further from the track than during other recent intense cyclones that had smaller
      circulation sizes. Just over 15% (3,834 km2) of the total reef area of the GBRMP
      is estimated to have sustained some level of coral damage, with ~4% (949 km2)
      sustaining a degree of structural damage. TC Yasi likely caused the greatest loss
      of coral cover on the GBR in a 24-hour period since 1985. Severely impacted reefs
      have started to recover; coral cover increased an average of 4% between 2011 and
      2013 at re-surveyed reefs. The in situ assessment of impacts described here is
      the largest in scale ever conducted on the Great Barrier Reef following a reef
      health disturbance. 

PMID- 25874719
TI  - How to get all trials reported: audit, better data, and individual
      accountability.

PMID- 25874720
TI  - Effects of low-level carotid baroreflex stimulation on atrial electrophysiology.
AB  - PURPOSE: This study aimed to investigate the effects of low-level carotid
      baroreflex stimulation (LL-CBS) on atrial electrophysiology. METHODS: In protocol
      1 (LL-CBS on physiological state), anesthetized rabbits were subjected to LL-CBS
      (n = 10) or surgical exposure (n = 6) for 1 h. In protocol 2 (LL-CBS on acute
      rapid atrial pacing), anesthetized rabbits underwent 3 h of rapid atrial pacing
      (RAP) with concomitant LL-CBS in the third hour (n = 7) or 3h-RAP without LL-CBS
      (n = 6). Carotid baroreceptor surrounded by electrodes allowed LL-CBS at 20 %
      below the voltage required to reduce systolic blood pressure or heart rate.
      Effective refractory period (ERP) and monophasic action potential duration (MAPD)
      were determined, and power spectral of heart rate variability (HRV) was analyzed
      at baseline as well as after interventions in all groups, respectively. RESULTS:
      In protocol 1, LL-CBS significantly prolonged the ERPs, MAPD90, and MAPD50 and
      increased high-frequency (HF) HRV component but it decreased low-frequency (LF)
      HRV component and LF/HF ratio. In protocol 2, 3h-RAP significantly shortened
      ERPs, MAPD90, and MAPD50 and decreased HF but it increased LF and LF/HF ratio.
      However, LL-CBS reversed the variations caused by RAP. CONCLUSIONS: LL-CBS
      prolongs ERPs and MAPD of the left atrium and attenuates RAP-induced atrial
      electrical remodeling including the shortening of ERPs and MAPD, probably by
      modulating the autonomic nervous system.

PMID- 25874721
TI  - Spatial distribution of an uranium-respiring betaproteobacterium at the Rifle, CO
      field research site.
AB  - The Department of Energy's Integrated Field-Scale Subsurface Research Challenge
      Site (IFRC) at Rifle, Colorado was created to address the gaps in knowledge on
      the mechanisms and rates of U(VI) bioreduction in alluvial sediments. Previous
      studies at the Rifle IFRC have linked microbial processes to uranium
      immobilization during acetate amendment. Several key bacteria believed to be
      involved in radionuclide containment have been described; however, most of the
      evidence implicating uranium reduction with specific microbiota has been
      indirect. Here, we report on the cultivation of a microorganism from the Rifle
      IFRC that reduces uranium and appears to utilize it as a terminal electron
      acceptor for respiration with acetate as electron donor. Furthermore, this
      bacterium constitutes a significant proportion of the subsurface sediment
      community prior to biostimulation based on TRFLP profiling of 16S rRNA genes. 16S
      rRNA gene sequence analysis indicates that the microorganism is a
      betaproteobacterium with a high similarity to Burkholderia fungorum. This is, to
      our knowledge, the first report of a betaproteobacterium capable of uranium
      respiration. Our results indicate that this microorganism occurs commonly in
      alluvial sediments located between 3-6 m below ground surface at Rifle and may
      play a role in the initial reduction of uranium at the site. 

PMID- 25874722
TI  - Fetal and umbilical Doppler ultrasound in normal pregnancy.
AB  - BACKGROUND: One of the main aims of routine antenatal care is to identify the 'at
      risk' fetus in order to apply clinical interventions which could result in
      reduced perinatal morbidity and mortality. Doppler ultrasound study of umbilical
      artery waveforms helps to identify the compromised fetus in 'high-risk'
      pregnancies and, therefore, deserves assessment as a screening test in 'low-risk'
      pregnancies. OBJECTIVES: To assess the effects on obstetric practice and
      pregnancy outcome of routine fetal and umbilical Doppler ultrasound in unselected
      and low-risk pregnancies. SEARCH METHODS: We searched the Cochrane Pregnancy and
      Childbirth Group Trials Register (28 February 2015) and reference lists of
      retrieved studies. SELECTION CRITERIA: Randomised and quasi-randomised controlled
      trials of Doppler ultrasound for the investigation of umbilical and fetal vessels
      waveforms in unselected pregnancies compared with no Doppler ultrasound. Studies
      where uterine vessels have been assessed together with fetal and umbilical
      vessels have been included. DATA COLLECTION AND ANALYSIS: Two review authors
      independently assessed the studies for inclusion, assessed risk of bias and
      carried out data extraction. In addition to standard meta-analysis, the two
      primary outcomes and five of the secondary outcomes were assessed using GRADE
      software and methodology. MAIN RESULTS: We included five trials that recruited
      14,624 women, with data analysed for 14,185 women. All trials had adequate
      allocation concealment, but none had adequate blinding of participants, staff or
      outcome assessors. Overall and apart from lack of blinding, the risk of bias for
      the included trials was considered to be low.Overall, routine fetal and umbilical
      Doppler ultrasound examination in low-risk or unselected populations did not
      result in increased antenatal, obstetric and neonatal interventions. There were
      no group differences noted for the review's primary outcomes of perinatal death
      and neonatal morbidity. Results for perinatal death were as follows: (average
      risk ratio (RR) 0.80, 95% confidence interval (CI) 0.35 to 1.83; four studies,
      11,183 participants). Only one included trial assessed serious neonatal morbidity
      and found no evidence of group differences (RR 0.99, 95% CI 0.06 to 15.75; one
      study, 2016 participants).For the comparison of a single Doppler assessment
      versus no Doppler, evidence for group differences in perinatal death was detected
      (RR 0.36, 95% CI 0.13 to 0.99; one study, 3891 participants). However, these
      results are based on a single trial, and we would recommend caution when
      interpreting this finding.There was no evidence of group differences for the
      outcomes of caesarean section, neonatal intensive care admissions or preterm
      birth less than 37 weeks.When the quality of the evidence for the main comparison
      of 'All Doppler versus no Doppler' was assessed with GRADE software, the outcomes
      of perinatal death and serious neonatal morbidity data were graded as of low
      quality. Evidence for the outcome of stillbirth was graded according to regimen
      subgroups - with a moderate quality rating for stillbirth (fetal/umbilical
      vessels only) and a low quality rating for stillbirth (fetal/umbilical vessels +
      uterine artery vessels). Evidence for admission to neonatal intensive care unit
      was assessed as of moderate quality, and evidence for the outcomes of caesarean
      section and preterm birth less than 37 weeks was graded as of high quality.There
      is no available evidence to assess the effect on substantive long-term outcomes
      such as childhood neurodevelopment and no data to assess maternal outcomes,
      particularly maternal satisfaction. AUTHORS' CONCLUSIONS: Existing evidence does
      not provide conclusive evidence that the use of routine umbilical artery Doppler
      ultrasound, or combination of umbilical and uterine artery Doppler ultrasound in
      low-risk or unselected populations benefits either mother or baby. Future studies
      should be designed to address small changes in perinatal outcome, and should
      focus on potentially preventable deaths.

PMID- 25874724
TI  - Patient navigators for people with chronic disease: protocol for a systematic
      review and meta-analysis.
AB  - BACKGROUND: Individuals with chronic diseases may have difficulty optimizing
      their health and getting the care they need due to a combination of patient,
      provider, and health system level barriers. Patient navigator programs, in which
      trained personnel assess and assist patients in overcoming barriers to care, may
      improve care and outcomes for patients with chronic disease by providing an
      alternative approach to conventional information and support resources. METHODS:
      This systematic review will evaluate the evidence for patient navigator programs,
      compared to usual care, in patients with chronic disease. We will include RCTs,
      cluster RCTs, and quasi-randomized RCTs that study the effects of patient
      navigator programs on clinical outcomes, patient experience, and markers of
      adherence to care. Studies will be identified by searching MEDLINE, Embase, the
      Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL, PsycINFO,
      Social Work Abstracts, and the references of included studies. Two authors will
      screen titles and abstracts independently. Full texts will be reviewed for
      relevance and data extraction will be done independently by two authors. Studies
      will be included if they assess patients of any age with one or more chronic
      diseases. Outcomes will be categorized into groups characterized by their
      proximity to mechanism of action of the intervention: patient-level outcomes,
      intermediate outcomes, and process outcomes. Descriptive data about the elements
      of the patient navigator intervention will also be collected for potential
      subgroup analyses. Risk of bias will be assessed using the Effective Practice and
      Organisation of Care Group (EPOC) risk of bias tool. Data will be analyzed using
      random effects meta-analysis (relative risk for dichotomous data and mean
      difference for continuous data), if appropriate. DISCUSSION: A comprehensive
      review of patient navigator programs, including a summary of the elements of
      programs that are associated with a successful intervention, does not yet exist.
      This systematic review will synthesize the evidence of the effect of patient
      navigator interventions on clinical and patient-oriented outcomes in populations
      across a comprehensive set of chronic diseases. SYSTEMATIC REVIEW REGISTRATION:
      PROSPERO CRD42013005857 .

PMID- 25874723
TI  - Potent functional antibody responses elicited by HIV-I DNA priming and boosting
      with heterologous HIV-1 recombinant MVA in healthy Tanzanian adults.
AB  - Vaccine-induced HIV antibodies were evaluated in serum samples collected from
      healthy Tanzanian volunteers participating in a phase I/II placebo-controlled
      double blind trial using multi-clade, multigene HIV-DNA priming and recombinant
      modified vaccinia Ankara (HIV-MVA) virus boosting (HIVIS03). The HIV-DNA vaccine
      contained plasmids expressing HIV-1 gp160 subtypes A, B, C, Rev B, Gag A, B and
      RTmut B, and the recombinant HIV-MVA boost expressed CRF01_AE HIV-1 Env subtype E
      and Gag-Pol subtype A. While no neutralizing antibodies were detected using
      pseudoviruses in the TZM-bl cell assay, this prime-boost vaccination induced
      neutralizing antibodies in 83% of HIVIS03 vaccinees when a peripheral blood
      mononuclear cell (PBMC) assay using luciferase reporter-infectious molecular
      clones (LucR-IMC) was employed. The serum neutralizing activity was significantly
      (but not completely) reduced upon depletion of natural killer (NK) cells from
      PBMC (p=0.006), indicating a role for antibody-mediated Fcgamma-receptor
      function. High levels of antibody-dependent cellular cytotoxicity (ADCC)
      mediating antibodies against CRF01_AE and/or subtype B were subsequently
      demonstrated in 97% of the sera of vaccinees. The magnitude of ADCC-mediating
      antibodies against CM235 CRF01_AE IMC-infected cells correlated with neutralizing
      antibodies against CM235 in the IMC/PBMC assay. In conclusion, HIV-DNA priming,
      followed by two HIV-MVA boosts elicited potent ADCC responses in a high
      proportion of Tanzanian vaccinees. Our findings highlight the potential of HIV
      DNA prime HIV-MVA boost vaccines for induction of functional antibody responses
      and suggest this vaccine regimen and ADCC studies as potentially important new
      avenues in HIV vaccine development. TRIAL REGISTRATION: Controlled-Trials
      ISRCTN90053831 The Pan African Clinical Trials Registry ATMR2009040001075080
      (currently PACTR2009040001075080).

PMID- 25874725
TI  - Adsorption of carbon monoxide on the pristine, B- and Al-doped C3N nanosheets.
AB  - The potential application of the intrinsic and extrinsic (8,0) zigzag single
      walled C3N nansheets as chemical sensor for CO molecules has been investigated
      using density functional theory calculations. The calculation shows that the
      pristine sheet is a semiconductor with a HOMO-LUMO gap (Eg) of about 2.19 eV. The
      pristine and B-doped sheets can weakly adsorb a CO molecule with the adsorption
      energies of -4.8 and -4.6 kcal mol(-1), and their electronic properties are not
      sensitive to this molecule. By replacing a C atom with an Al atom, localized
      impurity states are induced under the conduction level of the sheet. The binding
      interaction between the CO molecule and the Al-doped sheet becomes much stronger
      (Ead = -17.8 kcal mol(-1)). After the adsorption of CO on the Al-dope sheet, the
      Eg of the sheet is significantly decreased from 1.07 to 0.73 eV. This leads to a
      sizable increase in the resistance of the tube. Thus, the Al-doped sheet can show
      the presence of CO molecules by an electronic signal because of the change in its
      resistance and conductivity. 

PMID- 25874726
TI  - Characteristics of a large mumps outbreak: Clinical severity, complications and
      association with vaccination status of mumps outbreak cases.
AB  - In recent years, large mumps outbreaks, involving mainly adolescents and young
      adults, have re-emerged in several countries. We investigated a large mumps
      outbreak, evaluated the association between mumps clinical severity
      (complications, hospitalization) and vaccination status (number of previous
      measles, mumps and rubella - MMR vaccine doses), and assessed vaccine
      effectiveness. The first mumps cases emerged in an ultra-orthodox boys' school in
      Jerusalem and were epidemiologically linked to the mumps outbreak in New York.
      Overall, 3130 mumps cases were notified in the Jerusalem district during
      September 2009-August 2011 (median age 13y, 64% males). Most cases were reported
      from community clinics. Patients with systemic symptoms and/or complications
      (419, 13.4%) were either hospitalized (n = 79) or treated in an emergency medical
      center (n = 340). The main complications included orchitis (3.8% males> age 12y)
      and meningoencephalitis (0.5%). The mumps virus genotype was G5. The distribution
      of previous MMR vaccine doses (n = 0,1,2) was: 24.8%, 28.3% and 46.9%,
      respectively. The number of previous vaccine doses was inversely associated with
      clinical severity. Adjusted values for MMR vaccine effectiveness against
      complications were estimated as 52.1% (95% CI -4 -78%) for one vaccine dose and
      62.7% (95% CI 25.7-81.3%) for 2 doses. The outbreak was characterized by
      predominance of male students; the majority of whom had been previously
      vaccinated. The reported complication rate was relatively low. Vaccination status
      was associated with age and disease severity. The combination of limited mumps
      vaccine effectiveness and the specific school setting (dense learning and living
      conditions) probably contributed to the disease spread.

PMID- 25874727
TI  - Reprocessing and Recycling of Highly Cross-Linked Ion-Conducting Networks through
      Transalkylation Exchanges of C-N Bonds.
AB  - Exploiting exchangeable covalent bonds as dynamic cross-links recently afforded a
      new class of polymer materials coined as vitrimers. These permanent networks are
      insoluble and infusible, but the network topology can be reshuffled at high
      temperatures, thus enabling glasslike plastic deformation and reprocessing
      without depolymerization. We disclose herein the development of functional and
      high-value ion-conducting vitrimers that take inspiration from poly(ionic
      liquid)s. Tunable networks with high ionic content are obtained by the solvent-
      and catalyst-free polyaddition of an alpha-azide-omega-alkyne monomer and
      simultaneous alkylation of the resulting poly(1,2,3-triazole)s with a series of
      difunctional cross-linking agents. Temperature-induced transalkylation exchanges
      of C-N bonds between 1,2,3-triazolium cross-links and halide-functionalized
      dangling chains enable recycling and reprocessing of these highly cross-linked
      permanent networks. They can also be recycled by depolymerization with specific
      solvents able to displace the transalkylation equilibrium, and they display a
      great potential for applications that require solid electrolytes with excellent
      mechanical performances and facile processing such as supercapacitors, batteries,
      fuel cells, and separation membranes. 

PMID- 25874728
TI  - A new aliphatic alcohol and cytotoxic chemical constituents from Acorus gramineus
      rhizomes.
AB  - A new aliphatic alcohol, (2R,6R)-oct-7-ene-2,6-diol (1), and seven other known
      compounds (2-8) were isolated from Acorus gramineus rhizomes. The structure of 1
      was elucidated by a combination of extensive spectroscopic analyses, including 2D
      NMR, HR-MS, and the modified Mosher's method. Compounds 3-8 displayed consistent
      antiproliferative activities against the cell lines tested with IC50 values
      ranging from 7 to 48 MUm.

PMID- 25874729
TI  - Sugars as solid dispersion carrier to improve solubility and dissolution of the
      BCS class II drug: clotrimazole.
AB  - Solid dispersion of poorly soluble BCS class II drug, clotrimazole, was prepared
      with the aim of enhancing its dissolution profile. Solid dispersions were
      prepared using various sugars as carriers at different weight ratio to drug-like
      d-mannitol, d-fructose, d-dextrose and d-maltose by fusion method. The solubility
      of plain clotrimazole in different percent of sugar solutions was measured. Also,
      its solubility in solid dispersion and their physical mixture were assessed. The
      dissolution of all the prepared SD tablets, direct compressed clotrimazole tablet
      and plain drug were tested using the U.S. Pharmacopeia convention (USP) apparatus
      II. The dissolution profiles were characterized by parameters like area under
      curve (AUC), mean residence time (MRT), mean dissolution time (MDT) and percent
      dissolution efficiency (% DE). The release kinetics study was performed using DD
      Solver TM software. The selected solid dispersions (SDs) were evaluated for
      antifungal activity. A 100% solution of mannitol showed 806-fold increases in
      solubility as compared with plain clotrimazole in water. It was observed that the
      dissolution profile of clotrimazole was improved by mannitol SD at drug to sugar
      ration of 1:3. The percent DE value for mannitol SD tablet was found to be
      77.3516% as against plain drug and directly compressed tablet of clotrimazole at
      50.9439% and 31.33%, respectively. Also the antifungal activity indicated by
      inhibition zone was found to be 54 mm indicating enhance activity against Candida
      albicans as compared with plain CTZ at 6.6 mm. Thus, it can be concluded that the
      sugar alcohol, that is, mannitol is a more promising hydrophilic carrier for
      solid dispersion preparation to improve the solubility and dissolution of poorly
      soluble drugs.

PMID- 25874730
TI  - Top 10 research questions related to physical activity and multiple sclerosis.
AB  - An estimated 2.5 million people worldwide are living with multiple sclerosis
      (MS), and this disease may be increasing in prevalence. MS is a disease of the
      central nervous system that is associated with heterogeneous symptoms and
      functional consequences, and the current first-line disease-modifying therapies
      often become ineffective later in the disease. There is increasing evidence for
      the benefits of physical activity (PA) in people with MS, but this population is
      generally physically inactive and sedentary. We proposed 10 research questions to
      guide future research on PA and MS: (1) Is PA an MS disease-modifying behavior?
      (2) What are the benefits of PA among people with MS? (3) What is the optimal PA
      prescription for people with MS? (4) What are the safety issues with PA in people
      with MS? (5) What characteristics of people with MS modify the benefits of PA?
      (6) What variables explain participation in PA among people with MS? (7) What are
      effective behavioral interventions for PA change in people with MS? (8) How do we
      translate PA research into clinical MS practice? (9) What is the role of
      sedentary behavior in people with MS? And (10) what is the optimal measurement of
      PA in people with MS? These questions are critical for informing our
      understanding of the short- and long-term consequences of PA in MS as well as for
      identifying approaches for promoting and sustaining PA in MS. Addressing these
      questions may greatly improve the lives of people with this chronic disease. 

PMID- 25874732
TI  - Quantification of visual characteristics of whipped cream by image analysis and
      machine vision: method development.
AB  - The appearance (color, shine, surface roughness, bumpiness, view area, height) of
      whipped cream samples change with time. Quantitative methods based on image
      analysis were developed to measure these parameters in cream samples stored at 3
      temperatures (room temperature, 10  degrees C and 2  degrees C) for up to 24 h.
      There was a small decrease in L* and a* values over time, and a significant
      increase in b* values. DeltaE values suggest that these color changes are
      significant and observable (2.96 for room temperature, 9.46 for 10  degrees C,
      12.6 for 2  degrees C). Difference between polarized and nonpolarized images was
      used to quantify shine. The length of a laser line over the cream sample was
      measured to quantify the change in bumpiness of the surface (33.8%, 41.78%, and
      33.27% reduction in laser line length for room temperature, 10  degrees C, and 2 
      degrees C, respectively). For room temperature stored samples, most changes
      occurred during the first 5 min. For samples stored at 10  degrees C and 2 
      degrees C, most changes occurred during the first 30 min. Turn angles data did
      not provide useful information. The changes in view area depended on temperature:
      at room temperature the area increased over time, at 10  degrees C it increased
      first then decreased; at 2  degrees C the view area decreased over time.
      Correlation of the results of these methods with sensory evaluation can make the
      evaluation of the appearance of whipped cream more objective, repeatable, and
      quantitative. 

PMID- 25874731
TI  - Exploring the opportunities for food and drink purchasing and consumption by
      teenagers during their journeys between home and school: a feasibility study
      using a novel method.
AB  - OBJECTIVE: To investigate the feasibility and acceptability of using wearable
      cameras as a method to capture the opportunities for food and drink
      purchasing/consumption that young people encounter on their regular journeys to
      and from school. DESIGN: A qualitative study using multiple data-collection
      methods including wearable cameras, global positioning system units, individual
      interviews, food and drink purchase and consumption diaries completed by
      participants over four days, and an audit of food outlets located within an 800 m
      Euclidean buffer zone around each school. SETTING: A community setting. SUBJECTS:
      Twenty-two students (fourteen girls and eight boys) aged 13-15 years recruited
      from four secondary schools in two counties of England. RESULTS: Wearable cameras
      offered a feasible and acceptable method for collecting food purchase and
      consumption data when used alongside traditional methods of data collection in a
      small number of teenagers. We found evidence of participants making deliberate
      choices about whether or not to purchase/consume food and drink on their
      journeys. These choices were influenced by priorities over money, friends,
      journey length, travel mode and ease of access to opportunities for
      purchase/consumption. Most food and drink items were purchased/consumed within an
      800 m Euclidean buffer around school, with items commonly selected being high in
      energy, fat and sugar. Wearable camera images combined with interviews helped
      identify unreported items and misreporting errors. CONCLUSIONS: Wearable camera
      images prompt detailed discussion and generate contextually specific information
      which could offer new insights and understanding around eating behaviour
      patterns. The feasibility of scaling up the use of these methods requires further
      empirical work.

PMID- 25874733
TI  - Concurrent Vismodegib and Radiotherapy for Recurrent, Advanced Basal Cell
      Carcinoma.
AB  - IMPORTANCE: Vismodegib is a targeted agent recently approved for treating
      patients who develop recurrent or locally advanced basal cell carcinoma (BCC),
      and will inevitably be integrated into existing therapy for advanced BCC as it
      becomes increasingly used. Improved understanding of how vismodegib interacts
      with other treatment modalities, including radiotherapy, would help optimize
      multidisciplinary therapy and clinical outcomes. OBSERVATIONS: We report 2 cases
      of recurrent, advanced BCC treated from April 1, 2012, through October 31, 2014,
      with concurrent radiotherapy and vismodegib. Concurrent treatment appeared to be
      well tolerated and efficacious, with both patients having no evidence of
      progressive disease at last follow-up. CONCLUSIONS AND RELEVANCE: We found that
      the combination of vismodegib and radiotherapy is feasible for patients with
      recurrent or locally advanced BCC and that combined use of currently available
      therapies for advanced BCC warrants further prospective study.

PMID- 25874734
TI  - Association between fraction of exhaled nitrous oxide, bronchodilator response
      and inhaled corticosteroid type.
AB  - BACKGROUND: Fraction of exhaled nitrous oxide (FeNO) is a known marker of airway
      inflammation and a topic of recent investigation for asthma control in children.
      OBJECTIVE: To investigate the relationship among FeNO and bronchodilator response
      measured by spirometry and types of inhaled corticosteroids (ICS). METHODS: A one
      year review of children tested with spirometry and FeNO in a regional pediatric
      asthma centre was conducted. RESULTS: A total of 183 children were included (mean
      [+/- SD] age 12.8 +/- 2.8 years). Fluticasone was used most commonly (n=66
      [36.1%]), followed by ciclesonide (n=50 [27.3%]). Most children (n=73 [39.9%])
      had moderate persistent asthma. Increased FeNO was associated with percent change
      in forced expiratory volume in 1 s (FEV1) after bronchodilator adjusted for
      allergic rhinitis, parental smoking and ICS type (B=0.08 [95% CI 0.04 to 0.12];
      P<0.001). Similarly, FeNO was associated with percent change in forced expiratory
      flow at 25% to 75% of the pulmonary volume (FEF25-75) after bronchodilator
      adjusted for parental smoking and ICS type (B=0.13 [95% CI 0.01 to 0.24];
      P=0.03). FeNO accounted for only 16% and 9% of the variability in FEV1 and FEF25
      75, respectively. Mean-adjusted FeNO was lowest in fluticasone users compared
      with no ICS (mean difference 18.6 parts per billion [ppb] [95% CI 1.0 to 36.2])
      and there was no difference in adjusted FeNO level between ciclesonide and no ICS
      (5.9 ppb [95% CI -9.0 to 20.8]). CONCLUSION: FeNO levels correlated with
      bronchodilator response in a regional pediatric asthma centre. However, FeNO
      accounted for only 16% and 9% of the variability in FEV1 and FEF25-75,
      respectively. Mean adjusted FeNO varied according to ICS type, suggesting a
      difference in relative efficacy between ICS beyond their dose equivalents.

PMID- 25874736
TI  - Effects of one-week tongue task training on sleep apnea severity: A pilot study.
AB  - The aim of the present study was to assess the effects of one-week tongue-task
      training (TTT) on sleep apnea severity in sleep apnea subjects. Ten patients with
      sleep apnea (seven men, mean [+/- SD] age 52 +/- 8 years; mean apnea-hypopnea
      [AHI] index 20.9 +/- 5.3 events/h) underwent 1 h TTT in the authors' laboratory
      on seven consecutive days. A complete or limited recording and tongue maximal
      protruding force were assessed before and after one-week TTT. One-week TTT was
      associated with a global AHI decrease (pre-TTT: 20.9 +/- 5.3 events/h; post-TTT:
      16.1 +/- 5.1 events/h; P<0.001) and AHI decrease during rapid eye movement sleep
      (pre-TTT: 32.2 +/- 18.4 events/h; post-TTT: 16.7 +/- 6.6 events/h; P=0.03), while
      protruding force remained unchanged. The authors consider these results to be
      potentially clinically relevant and worthy of further investigation in a large
      randomized trial.

PMID- 25874737
TI  - [Cardiac effects of hypertension].

PMID- 25874735
TI  - Bronchiectasis exacerbations: The role of atypical bacteria, respiratory
      syncytial virus and pulmonary function tests.
AB  - BACKGROUND: Aside from the known role of common bacteria, there is a paucity of
      data regarding the possible role of atypical bacteria and viruses in
      exacerbations of non-cystic fibrosis bronchiectasis. OBJECTIVE: To explore the
      possible role of atypical bacteria (namely, Mycoplasma pneumoniae and
      Chlamydophila pneumoniae) and respiratory syncytial virus (RSV) as causative
      agents of bronchiectasis exacerbations. METHODS: A cohort of 33 patients was
      studied over a two-year period (one year follow-up for each patient). Polymerase
      chain reaction for the detection of M pneumoniae, C pneumoniae and RSV in
      bronchoalveolar lavage samples were performed during all visits. Antibody titres
      (immunoglobulin [Ig]M and IgG) against the aforementioned pathogens were also
      measured. In addition, cultures for common bacteria and mycobacteria were
      performed from the bronchoalveolar lavage samples. RESULTS: Fifteen patients
      experienced a total of 19 exacerbations during the study period. Although RSV was
      detected by polymerase chain reaction during stable visits in four patients, it
      was never detected during an exacerbation. M pneumoniae and C pneumoniae were
      never detected at stable visits or during exacerbations. IgM antibody titres for
      these three pathogens were negative in all patient visits. CONCLUSIONS: Atypical
      pathogens and RSV did not appear to be causative agents of bronchiectasis
      exacerbations.

PMID- 25874738
TI  - [A 73-year-old female patient after liver and kidney transplantation with dull
      pain in the epigastrium and recurrent epistaxis].
AB  - A 73-year-old female patient who had received a liver and kidney transplantation
      presented with symptomatic pancytopenia and right-sided upper abdominal pain. The
      histological investigation of a bone marrow biopsy showed the extremely rare
      manifestation of a disseminated Merkel cell carcinoma with infiltration of the
      bone marrow and suppression of hematopoiesis. Also a Coombs test positive
      hemolytic anemia did not show a significant response to high-dose steroid
      therapy. Palliative chemotherapy with carboplatin and etoposide at reduced dosage
      had to be terminated due to deterioration of the patient's general condition. The
      patient died 2 days after initiation of chemotherapy.

PMID- 25874739
TI  - Ambient mass spectrometry imaging metabolomics method provides novel insights
      into the action mechanism of drug candidates.
AB  - Elucidation of the mechanism of action for drug candidates is fundamental to drug
      development, and it is strongly facilitated by metabolomics. Herein, we developed
      an imaging metabolomics method based on air-flow-assisted desorption electrospray
      ionization mass spectrometry imaging (AFADESI-MSI) under ambient conditions. This
      method was subsequently applied to simultaneously profile a novel anti-insomnia
      drug candidate, N(6)-(4-hydroxybenzyl)-adenosine (NHBA), and various endogenous
      metabolites in rat whole-body tissue sections after the administration of NHBA.
      The principal component analysis (PCA) represented by an intuitive color-coding
      scheme based on hyperspectral imaging revealed in situ molecular profiling
      alterations in response to stimulation of NHBA, which are in a very low intensity
      and hidden in massive interferential peaks. We found that the abundance of six
      endogenous metabolites changed after drug administration. The spatiotemporal
      distribution indicated that five altered molecules-including neurotransmitter
      gamma-aminobutyric acid, neurotransmitter precursors choline and
      glycerophosphocholine, energy metabolism-related molecules adenosine (an
      endogenous sleep factor), and creatine-are closely associated with insomnia or
      other neurological disorders. These findings not only provide insights into a
      deep understanding on the mechanism of action of NHBA, but also demonstrate that
      the AFADESI-MSI-based imaging metabolomics is a powerful technique to investigate
      the molecular mechanism of drug action, especially for drug candidates with
      multitarget or undefined target in the preclinical study stage.

PMID- 25874740
TI  - Epigenetics: Characterizing enhancers with dCas9.

PMID- 25874741
TI  - Synthesis-atomic structure-properties relationships in metallic nanoparticles by
      total scattering experiments and 3D computer simulations: case of Pt-Ru nanoalloy
      catalysts.
AB  - An approach to determining the 3D atomic structure of metallic nanoparticles
      (NPs) in fine detail and using the unique knowledge obtained for rationalizing
      their synthesis and properties targeted for optimization is described and
      exemplified on Pt-Ru alloy NPs of importance to the development of devices for
      clean energy conversion such as fuel cells. In particular, PtxRu100-x alloy NPs,
      where x = 31, 49 and 75, are synthesized by wet chemistry and activated
      catalytically by a post-synthesis treatment involving heating under controlled N2
      H2 atmosphere. So-activated NPs are evaluated as catalysts for gas-phase CO
      oxidation and ethanol electro-oxidation reactions taking place in fuel cells.
      Both as-synthesized and activated NPs are characterized structurally by total
      scattering experiments involving high-energy synchrotron X-ray diffraction
      coupled to atomic pair distribution functions (PDFs) analysis. 3D structure
      models both for as-synthesized and activated NPs are built by molecular dynamics
      simulations based on the archetypal for current theoretical modelling Sutton-Chen
      method. Models are refined against the experimental PDF data by reverse Monte
      Carlo simulations and analysed in terms of prime structural characteristics such
      as metal-to-metal bond lengths, bond angles and first coordination numbers for Pt
      and Ru atoms. Analysis indicates that, though of a similar type, the atomic
      structure of as-synthesized and respective activated NPs differ in several
      details of importance to NP catalytic properties. Structural characteristics of
      activated NPs and data for their catalytic activity are compared side by side and
      strong evidence found that electronic effects, indicated by significant changes
      in Pt-Pt and Ru-Ru metal bond lengths at NP surface, and practically unrecognized
      so far atomic ensemble effects, indicated by distinct stacking of atomic layers
      near NP surface and prevalence of particular configurations of Pt and Ru atoms in
      these layers, contribute to the observed enhancement of the catalytic activity of
      PtxRu100-x alloy NPs at x ~ 50. Implications of so-established relationships
      between the atomic structure and catalytic activity of Pt-Ru alloy NPs on efforts
      aimed at improving further the latter by tuning-up the former are discussed and
      the usefulness of detailed NP structure studies to advancing science and
      technology of metallic NPs - exemplified. 

PMID- 25874742
TI  - In vitro comparison of endplate preparation between four mini-open interbody
      fusion approaches.
AB  - PURPOSE: Discectomy and endplate preparation are important steps in interbody
      fusion for ensuring sufficient arthrodesis. While modern less-invasive approaches
      for lumbar interbody fusion have gained in popularity, concerns exist regarding
      their ability to allow for adequate disc space and endplate preparation. Thus,
      the purpose of this study was to quantitatively and qualitatively evaluate and
      compare disc space and endplate preparation achieved with four less-invasive
      approaches for lumbar interbody fusion in cadaveric spines. METHODS: A total of
      24 disc spaces (48 endplates) from L2 to L5 were prepared in eight cadaveric
      torsos using mini-open anterior lumbar interbody fusion (mini-ALIF), minimally
      invasive posterior lumbar interbody fusion (MAS PLIF), minimally invasive
      transforaminal lumbar interbody fusion (MAS TLIF) or minimally invasive lateral,
      transpsoas interbody fusion (XLIF) on two specimens each, for a total of six
      levels and 12 endplates prepared per procedure type. Following complete
      discectomy and endplate preparation, spines were excised and split axially at the
      interbody disc spaces. Endplates were digitally photographed and evaluated using
      image analysis software. Area of endplate preparation was measured and
      qualitative evaluation was also performed to grade the quality of preparation.
      RESULTS: The XLIF approach resulted in the greatest relative area of endplate
      preparation (58.3 %) while mini-ALIF resulted in the lowest at 35.0 %. Overall,
      there were no differences in percentage of preparation between cranial and caudal
      endplates, though this was significantly different in the XLIF group (65 vs 52 %,
      respectively). ALL damage was observed in 3 MAS TLIF levels. Percentage of
      endplate that was deemed to have complete disc removal was highest in XLIF group
      with 90 % compared to 65 % in MAS TLIF group, 43 % in MAS PLIF, and 40 % in mini
      ALIF group. Endplate damage area was highest in the MAS TLIF group at 48 % and
      lowest in XLIF group at 4 %. CONCLUSIONS: These results demonstrate that adequate
      endplate preparation for interbody fusion can be achieved utilizing various
      minimally invasive approach techniques (mini-ALIF, MAS TLIF, MAS PLIF, XLIF),
      however, XLIF appears to provide a greater area of and more complete endplate
      preparation.

PMID- 25874743
TI  - Expert's comment concerning Grand Rounds case entitled "Solid aneurysmal bone
      cyst on the cervical spine of a young child" (L. Casabianca et al.).

PMID- 25874745
TI  - Exclusive self-aligned beta-phase PVDF films with abnormal piezoelectric
      coefficient prepared via phase inversion.
AB  - Self-polarised poly(vinylidene fluoride), (PVDF), films were prepared via a
      facile phase-inversion technique wherein the polymorphism of the films was
      controlled from exclusive alpha- (>90%) to beta-phase (>98%) by simply varying
      the quenching temperature from 100  degrees C to -20  degrees C, respectively. At
      low temperatures, the beta-phase crystallites were found to be self-aligned, with
      the PVDF thin films possessing a high piezoelectric coefficient of up to -49.6 pm
      V(-1). The extraordinarily high beta-phase and piezoelectric coefficient of these
      PVDF films make them suitable for electroactive and energy harvesting
      applications. 

PMID- 25874744
TI  - Can triggered electromyography monitoring throughout retraction predict
      postoperative symptomatic neuropraxia after XLIF? Results from a prospective
      multicenter trial.
AB  - PURPOSE: This multicenter study aims to evaluate the utility of triggered
      electromyography (t-EMG) recorded throughout psoas retraction during lateral
      transpsoas interbody fusion to predict postoperative changes in motor function.
      METHODS: Three hundred and twenty-three patients undergoing L4-5 minimally
      invasive lateral interbody fusion from 21 sites were enrolled. Intraoperative
      data collection included initial t-EMG thresholds in response to posterior
      retractor blade stimulation and subsequent t-EMG threshold values collected every
      5 min throughout retraction. Additional data collection included
      dimensions/duration of retraction as well as pre-and postoperative lower
      extremity neurologic exams. RESULTS: Prior to expanding the retractor, the
      lowestt-EMG threshold was identified posterior to the retractor in 94 % of cases.
      Postoperatively, 13 (4.5 %) patients had a new motor weakness that was consistent
      with symptomatic neuropraxia (SN) of lumbar plexus nerves on the approach side.
      There were no significant differences between patients with or without a
      corresponding postoperative SN with respect to initial posterior blade reading (p
      = 0.600), or retraction dimensions (p > 0.05). Retraction time was significantly
      longer in those patients with SN vs. those without (p = 0.031). Stepwise logistic
      regression showed a significant positive relationship between the presence of new
      postoperative SN and total retraction time (p < 0.001), as well as change in t
      EMG thresholds over time (p < 0.001), although false positive rates (increased
      threshold in patients with no new SN) remained high regardless of the absolute
      increase in threshold used to define an alarm criteria. CONCLUSIONS: Prolonged
      retraction time and coincident increases in t-EMG thresholds are predictors of
      declining nerve integrity. Increasing t-EMG thresholds, while predictive of
      injury, were also observed in a large number of patients without iatrogenic
      injury, with a greater predictive value in cases with extended duration. In
      addition to a careful approach with minimal muscle retraction and consistent
      lumbar plexus directional retraction, the incidence of postoperative motor
      neuropraxia may be reduced by limiting retraction time and utilizing t-EMG
      throughout retraction, while understanding that the specificity of this
      monitoring technique is low during initial retraction and increases with longer
      retraction duration.

PMID- 25874746
TI  - Downregulation of VANGL1 inhibits cellular invasion rather than cell motility in
      hepatocellular carcinoma cells without stimulation.
AB  - AIMS: The Wnt planar cell polarity (PCP) pathway is one of the Wnt pathways which
      plays a critical role in cell proliferation and fate. The VANGL1 protein is one
      of Wnt-PCP pathway components. It is known that Wnt-PCP pathway has major roles
      in cell motility but its role in hepatocellular carcinoma (HCC) progression
      through invasion and metastasis needs to be clarified. METHODS: We silenced
      VANGL1 gene expression in the HepG2 HCC cell line by stable transfection with a
      vector containing siRNA template for VANGL1 and investigated the change in cell
      invasion and motility. RESULTS: Transfected cells with the siRNA template showed
      significantly suppressed invasive capacity when compared to controls although
      cellular motility was only slightly affected. CONCLUSION: Our study showed a
      basal role for VANGL1 with respect to the invasive capacity of HCC cells. This
      suggests that the Wnt-PCP pathway may play a role in progression of HCC through
      cellular invasion but further studies are needed to clarify its role in cell
      motility.

PMID- 25874747
TI  - An exploratory efficacy study of the amyloid imaging agent [(18)F]flutemetamol in
      Japanese Subjects.
AB  - AIM: The aim of the study presented was to investigate the brain uptake
      properties of the amyloid PET agent [(18)F]flutemetamol in Japanese healthy
      controls and clinically probable Alzheimer's disease (AD) patients, and to make a
      comparison with the results of a previously performed study on Caucasian
      subjects. [(18)F]flutemetamol was recently approved by the American Food and Drug
      Administration and the European Medicines Agency for visualization of amyloid in
      vivo. Since the first clinical study of [(18)F]flutemetamol-an (18)F derivative
      of the PET tracer 11C-Pittsburgh Compound B targeting beta-amyloid--took place,
      several clinical studies have been performed, but few focusing on a Japanese
      population. METHODS: In the Step A, three elderly healthy volunteers and three AD
      subjects underwent dynamic PET scanning 0-30 and 60-150 min after injection of
      185 MBq [(18)F]flutemetamol. The brain volume of distribution (VT) was quantified
      using Logan's linear graphical analysis and as standardized uptake value ratios
      (SUVR) with a cerebellar reference. The optimal acquisition window was determined
      from brain time activity curves for Step B. In the Step B, 5 AD and 5 elderly
      healthy volunteers were scanned from 80 to 140 min after intravenous injection of
      [(18)F]flutemetamol. The data from the two parts were pooled for estimation of
      overall efficacy. RESULTS: [(18)F]Flutemetamol injection was shown to be safe-no
      serious adverse events were reported during this study. A simplified SUVR
      estimate of the uptake of [(18)F]flutemetamol using a time window of 85-115 min
      post injection successfully discriminated AD cases from healthy volunteers. AD
      subjects showed an elevated tracer uptake in prefrontal cortex, the lateral
      temporal cortex and precuneus amongst other regions. No significant
      [(18)F]flutemetamol PET differences could be seen between the Japanese AD cases
      in this study and those from an earlier Caucasian study, or between control
      subjects in Japanese and Caucasian studies. CONCLUSIONS: This study supports the
      use of [(18)F]flutemetamol PET in Japanese population as a marker of the presence
      of fibrillar beta-amyloid. The lack of differences between the Japanese cohort
      and those from a previous Caucasian cohort supports the extrapolation of results
      from other Caucasian [(18)F]flutemetamol PET studies to the Japanese population.

PMID- 25874748
TI  - Guns, Mental Illness, and the Law: Introduction to This Issue.
AB  - Firearm violence is a top-tier public health problem in the U.S., killing 33,563
      and injuring an additional 81,396 people in 2012 (Centers for Disease Control and
      Prevention, CDC, ). Given constitutional protection and the cultural entrenchment
      of private gun ownership in the U.S., it is likely that guns will remain widely
      accessible--and largely unrestricted--for the foreseeable future. Therefore, most
      policies and laws intended to reduce firearm violence focus selectively on
      preventing "dangerous people" from having access to guns. That is a formidable
      challenge. How do we think productively about guns and mental illness in this
      context, and about the role of law in lessening the toll of gun violence?

PMID- 25874749
TI  - Neural correlates of adolescents' viewing of parents' and peers' emotions:
      Associations with risk-taking behavior and risky peer affiliations.
AB  - Social reorientation from parents to same-age peers is normative in adolescence,
      but the neural correlates of youths' socioemotional processing of parents and
      peers have not been explored. In the current study, 22 adolescents (average age
      16.98) underwent neuroimaging (functional magnetic resonance imaging) while
      viewing and rating emotions shown in brief video clips featuring themselves,
      their parents, or an unfamiliar peer. Viewing self vs. other and parents vs. the
      peer activated regions in the medial prefrontal cortex, replicating prior
      findings that this area responds to self-relevant stimuli, including familiar and
      not just similar others. Viewing the peer compared with parents elicited
      activation in posterior 'mentalizing' structures, the precuneus, posterior
      cingulate cortex (PCC), bilateral posterior superior temporal sulcus and right
      temporoparietal junction, as well as the ventral striatum and bilateral amygdala
      and hippocampus. Relative activations in the PCC and precuneus to the peer vs.
      the parent were related both to reported risk-taking behavior and to affiliations
      with more risk-taking peers. The results suggest neural correlates of the
      adolescent social reorientation toward peers and away from parents that may be
      associated with adolescents' real-life risk-taking behaviors and social
      relationships. 

PMID- 25874750
TI  - Similar PAH fate in anaerobic digesters inoculated with three microbial
      communities accumulating either volatile fatty acids or methane.
AB  - Urban sludge produced on wastewater treatment plants are often contaminated by
      organic pollutants such as polycyclic aromatic hydrocarbons (PAH). Their removal
      under methanogenic conditions was already reported, but the factors influencing
      this removal remain unclear. Here, we determined the influence of microbial
      communities on PAH removal under controlled physico-chemical conditions. Twelve
      mesophilic anaerobic digesters were inoculated with three microbial communities
      extracted from ecosystems with contrasting pollution histories: a PAH
      contaminated soil, a PCB contaminated sediment and a low contaminated anaerobic
      sludge. These anaerobic digesters were operated during 100 days in continuous
      mode. A sterilised activated sludge, spiked with 13 PAH at concentrations usually
      encountered in full-scale wastewater treatment plants, was used as substrate. The
      dry matter and volatile solid degradation, the biogas production rate and
      composition, the volatile fatty acids (VFA) production and the PAH removals were
      monitored. Bacterial and archaeal communities were compared in abundance (qPCR),
      in community structure (SSCP fingerprinting) and in dominant microbial species
      (454-pyrosequencing). The bioreactors inoculated with the community extracted
      from low contaminated anaerobic sludge showed the greater methane production. The
      PAH removals ranged from 10% to 30%, respectively, for high and low molecular
      weight PAH, whatever the inoculums tested, and were highly correlated with the
      dry matter and volatile solid removals. The microbial community structure and
      diversity differed with the inoculum source; this difference was maintained after
      the 100 days of digestion. However, the PAH removal was not correlated to these
      diverse structures and diversities. We hence obtained three functional stable
      consortia with two contrasted metabolic activities, and three different pictures
      of microbial diversity, but similar PAH and matter removals. These results
      confirm that PAH removal depends on the molecule type and on the solid matter
      removal. But, as PAH elimination is similar whether the solid substrate is
      degraded into VFA or into methane, it seems that the fermentative communities are
      responsible for their elimination.

PMID- 25874751
TI  - Growth inhibition and stability of PgAFP from Penicillium chrysogenum against
      fungi common on dry-ripened meat products.
AB  - Dry-ripened foods favor the development of a superficial fungal population that
      may include toxigenic molds. To combat unwanted molds, an antifungal protein from
      Penicillium chrysogenum (PgAFP) can be useful. The aim of the present work was to
      study the antimicrobial activity of PgAFP against microorganisms common in dry
      ripened foods, and to evaluate its sensitivity to proteolytic enzymes and heat
      treatments that may be applied to foods, as well as to different pH values. The
      inhibitory effect of the purified protein on 38 microbial strains grown in
      culture medium was determined. PgAFP sensitivity to various proteases, heat
      treatments, and preincubation at different pH values was tested by means of the
      residual activity on selected reference strains. Inhibitory activity of PgAFP
      against unwanted molds was tested in a dry-fermented sausage. This protein
      exhibited potent inhibitory activity against unwanted molds, including the main
      mycotoxin-producing species of Aspergillus and Penicillium of concern for dry
      ripened foods. PgAFP withstood most proteases, intense heat and a wide range of
      pH values. PgAFP efficiently reduced counts of A. flavus and P. restrictum
      inoculated on a dry-fermented sausage. This protein can be of interest to control
      hazardous molds in dry-ripened foods. 

PMID- 25874752
TI  - Disentangling the effects of circulating IGF-1, glucose, and cortisol on features
      of perceived age.
AB  - Circulatory levels of insulin-like growth factor (IGF-1), glucose, and cortisol
      have been previously associated with facial aging. However, as these serum
      measures are related, it is unclear whether their associations with skin aging
      occur independently from each other. We aimed to investigate whether the
      associations between serum IGF-1, glucose, and cortisol levels and perceived
      age/wrinkle grade occur independently of each other and whether these are
      mediated via skin wrinkling or via other skin aging features. Perceived age and
      skin wrinkling grade were assessed in a random sample from the Leiden Longevity
      Study with non-fasted (N = 579) and fasted blood sampling (N = 219). In our study
      population, a higher non-fasted IGF-1 level was associated with a lower skin
      wrinkling grade (p value = 0.014) and tended to associate with a lower perceived
      age (p value = 0.067), which was mediated for approximately 100 % by skin
      wrinkling. A higher non-fasted glucose level was associated with a higher
      perceived age (p value = 0.017), which was mediated for 51 % by skin wrinkling
      grade (p value = 0.112). A higher fasted cortisol level tended to associate with
      a higher perceived age (p value = 0.116), which was mediated for 29 % by skin
      wrinkling. Results remained similar when the serum measures were statistically
      adjusted for each other. Thus, the previously reported serum measures associate
      independently from each other with skin aging. IGF-1 is predominantly associated
      with perceived age by skin wrinkling, whereas cortisol and glucose also by other
      skin aging features.

PMID- 25874753
TI  - A Comparison of Referred Sexual Partners to Their Community Recruited
      Counterparts in The BROTHERS Project (HPTN 061).
AB  - The BROTHERS Project (HPTN 061) was established to determine the feasibility and
      acceptability of a multi-component intervention among African American MSM to
      reduce HIV incidence. The goal of this analysis was to determine if the sexual
      partner referral approach used in HPTN 061 broadened the reach of recruitment
      with regards to characteristics associated with higher infection rates and
      barriers to quality health care. Overall, referred sexual partners had notable
      structural barrier differences in comparison to community-recruited participants:
      lower income, less education, higher unemployment, HIV positive diagnosis,
      incarceration history, and no health insurance. The study's findings pose
      implications for utilizing the sexual partner referral approach in reaching
      African American MSM who may not be accessed by traditional recruitment methods
      or who are well-integrated in health care systems. 

PMID- 25874754
TI  - Finding HIV in hard to reach populations: mobile HIV testing and geospatial
      mapping in Umlazi township, Durban, South Africa.
AB  - Mobile, community-based HIV testing may help achieve universal HIV testing in
      South Africa. We compared the yield, geographic distribution, and demographic
      characteristics of populations tested by mobile- and clinic-based HIV testing
      programs deployed by iThembalabantu Clinic in Durban, South Africa. From July to
      November 2011, 4,701 subjects were tested; HIV prevalence was 35 % among IPHC
      testers and 10 % among mobile testers (p < 0.001). Mobile testers varied in mean
      age (22-37 years) and % males (26-67 %). HIV prevalence at mobile sites ranged
      from 0 to 26 %. Testers traveled further than the clinic closest to their home;
      mobile testers were more likely to test >=5 km away from home. Mobile HIV testing
      can improve testing access and identify testing sites with high HIV prevalence.
      Individuals often access mobile testing sites farther from home than their
      nearest clinic. Geospatial techniques can help optimize deployment of mobile
      units to maximize yield in hard-to-reach populations. 

PMID- 25874755
TI  - Gastroparesis: A Review of Current Diagnosis and Treatment Options.
AB  - Gastroparesis (GP) is a chronic neuromuscular disorder of the upper
      gastrointestinal tract. The incidence of GP is not well described; however, the
      number of individuals affected by symptoms of GP in the United States is
      estimated to be over 4 million. The etiology of GP is diverse. Approximately 25%
      of cases are associated with diabetes, whereas nearly 50% are classified as
      idiopathic; many of these latter cases likely represent a postinfectious process.
      Connective tissue disorders, autoimmune disorders, prior gastric surgery,
      ischemia, and medications make up the vast majority of the remaining cases. The
      pathophysiology of GP is also diverse. Abnormalities in fundic tone,
      antroduodenal dyscoordination, a weak antral pump, gastric dysrhythmias, and
      abnormal duodenal feedback all contribute to delays in gastric emptying and
      symptom expression. Characteristic symptoms of GP include nausea, vomiting,
      epigastric pain, early satiety, and weight loss. The diagnosis of GP is made
      using a combination of characteristic symptoms in conjunction with objective
      evidence of delayed gastric emptying in the absence of mechanical obstruction.
      Once the diagnosis is made, treatment options include dietary modification,
      medications to accelerate gastric emptying, antiemetic agents, gastric electrical
      stimulation, and surgery. In the following sections we will provide an overview
      of the health care impact of GP, describe the underlying pathophysiology, and
      review treatment options using an evidence-based approach. 

PMID- 25874756
TI  - Biohydrogen production: strategies to improve process efficiency through
      microbial routes.
AB  - The current fossil fuel-based generation of energy has led to large-scale
      industrial development. However, the reliance on fossil fuels leads to the
      significant depletion of natural resources of buried combustible geologic
      deposits and to negative effects on the global climate with emissions of
      greenhouse gases. Accordingly, enormous efforts are directed to transition from
      fossil fuels to nonpolluting and renewable energy sources. One potential
      alternative is biohydrogen (H2), a clean energy carrier with high-energy yields;
      upon the combustion of H2, H2O is the only major by-product. In recent decades,
      the attractive and renewable characteristics of H2 led us to develop a variety of
      biological routes for the production of H2. Based on the mode of H2 generation,
      the biological routes for H2 production are categorized into four groups:
      photobiological fermentation, anaerobic fermentation, enzymatic and microbial
      electrolysis, and a combination of these processes. Thus, this review primarily
      focuses on the evaluation of the biological routes for the production of H2. In
      particular, we assess the efficiency and feasibility of these bioprocesses with
      respect to the factors that affect operations, and we delineate the limitations.
      Additionally, alternative options such as bioaugmentation, multiple process
      integration, and microbial electrolysis to improve process efficiency are
      discussed to address industrial-level applications. 

PMID- 25874757
TI  - Area-specific cell stimulation via surface-mediated gene transfer using apatite
      based composite layers.
AB  - Surface-mediated gene transfer systems using biocompatible calcium phosphate
      (CaP)-based composite layers have attracted attention as a tool for controlling
      cell behaviors. In the present study we aimed to demonstrate the potential of CaP
      based composite layers to mediate area-specific dual gene transfer and to
      stimulate cells on an area-by-area basis in the same well. For this purpose we
      prepared two pairs of DNA-fibronectin-apatite composite (DF-Ap) layers using a
      pair of reporter genes and pair of differentiation factor genes. The results of
      the area-specific dual gene transfer successfully demonstrated that the cells
      cultured on a pair of DF-Ap layers that were adjacently placed in the same well
      showed specific gene expression patterns depending on the gene that was
      immobilized in the underlying layer. Moreover, preliminary real-time PCR results
      indicated that multipotential C3H10T1/2 cells may have a potential to change into
      different types of cells depending on the differentiation factor gene that was
      immobilized in the underlying layer, even in the same well. Because DF-Ap layers
      have a potential to mediate area-specific cell stimulation on their surfaces,
      they could be useful in tissue engineering applications.

PMID- 25874758
TI  - Selection of reference genes for microRNA quantitative expression analysis in
      Chinese perch, Siniperca chuatsi.
AB  - Real-time quantitative reverse transcription PCR (RT-qPCR) is one of the most
      effective and sensitive techniques in gene expression assay, for which selection
      of reference genes is a prerequisite. In teleost species, such as Chinese perch,
      the expression profiling of miRNAs as reference genes for RT-qPCR has not been
      intensively studied. In the present study, the expression profiles of six miRNAs
      (miR-101a, miR-146a, miR-22a, miR-23a, miR-26a and let-7a) and one small nuclear
      RNA (U6) were assayed with RT-qPCR in different adult tissues, developmental
      stages and growth conditions of Chinese perch, Siniperca chuatsi. The analyses
      revealed that embryonic developmental stage is an important variability factor in
      the expression stability of miRNAs. All six miRNAs exhibited better expression
      consistency than U6 in most of the conditions examined, and therefore, they may
      be more suitable as a reference gene for miRNA quantification. When different
      tissues and developmental stages were considered, miR-22a demonstrated the most
      consistent expression pattern, and the best combination of reference genes was
      miR-22a and miR-23a. Our study offers useful data for selecting miRNAs as
      reference genes for RT-qPCR analysis of miRNAs in teleost fishes under different
      conditions. 

PMID- 25874759
TI  - Molecular characterization of Sec2 loci in wheat--Secale africanum derivatives
      demonstrates genomic divergence of Secale species.
AB  - The unique 75 K gamma-secalins encoded by Sec2 loci in Secale species is composed
      of almost half rye storage proteins. The chromosomal location of Sec2 loci in
      wild Secale species, Secale africanum, was carried out by the wheat--S. africanum
      derivatives, which were identified by genomic in situ hybridization and multi
      color fluorescence in situ hybridization. The Sec2 gene-specific PCR analysis
      indicated that the S. cereale Sec2 was located on chromosome 2R, while the S.
      africanum Sec2 was localized on chromosome 6Rafr of S. africanum. A total of 38
      Sec2 gene sequences were isolated from S. africanum, S. cereale and S. sylvestre
      by PCR-based cloning. Phylogenetic analysis showed that S. africanum Sec2
      diverged from S. cereale Sec2 approximately 2-3 million years ago. The
      illegitimate recombination of chromosome 2R-6R involving the Sec2 loci region may
      accelerate sequence variation during evolutionary process from wild to cultivated
      Secale species.

PMID- 25874760
TI  - Using a novel microRNA delivery system to inhibit osteoclastogenesis.
AB  - Previously, we developed a novel microRNA (miRNA) delivery system based on
      bacteriophage MS2 virus-like particles (MS2 VLPs). In this current study, we used
      this system to transport miR-146a into human peripheral blood mononuclear cells
      (PBMCs), and demonstrated the inhibition of osteoclastogenesis in precursors. Two
      cytokines, receptor activator of NF-kappaB ligand (RANKL), and macrophage-colony
      stimulating factor (M-CSF) were used to induce osteoclastogenesis. MS2 VLPs were
      transfected into PBMCs. qRT-PCR was applied to measure expression levels of miR
      146a and osteoclast (OC)-specific genes. Western blot (WB) was conducted to
      evaluate miR-146a downstream target proteins: epidermal growth factor receptor
      (EGFR) and tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6). The
      formation and activity of OCs were assessed by cytochemical staining and bone
      resorption assay, respectively. In PBMCs treated with MS2-miR146a VLPs, qRT-PCR
      assays showed increased expression of miR-146a (p < 0.01) and decreased
      expression of all four OC-specific genes (p < 0.05). WB results indicated
      decreased expression of EGFR (p < 0.01) and TRAF6 (p < 0.05). The number of OCs
      decreased markedly and bone resorption assay demonstrated inhibited activity.
      This miR-146a delivery system could be applied to induce overexpression of miR
      146a and to inhibit the differentiation and function of OCs. 

PMID- 25874761
TI  - Determination of oxidized phosphatidylcholines by hydrophilic interaction liquid
      chromatography coupled to Fourier transform mass spectrometry.
AB  - A novel liquid chromatography-mass spectrometry (LC-MS) approach for analysis of
      oxidized phosphatidylcholines by an Orbitrap Fourier Transform mass spectrometer
      in positive electrospray ionization (ESI) coupled to hydrophilic interaction
      liquid chromatography (HILIC) was developed. This method depends on three
      selectivity criteria for separation and identification: retention time, exact
      mass at a resolution of 100,000 and collision induced dissociation (CID) fragment
      spectra in a linear ion trap. The process of chromatography development showed
      the best separation properties with a silica-based Kinetex column. This type of
      chromatography was able to separate all major lipid classes expected in mammalian
      samples, yielding increased sensitivity of oxidized phosphatidylcholines over
      reversed phase chromatography. Identification of molecular species was achieved
      by exact mass on intact molecular ions and CID tandem mass spectra containing
      characteristic fragments. Due to a lack of commercially available standards,
      method development was performed with copper induced oxidation products of
      palmitoyl-arachidonoyl-phosphatidylcholine, which resulted in a plethora of lipid
      species oxidized at the arachidonoyl moiety. Validation of the method was done
      with copper oxidized human low-density lipoprotein (LDL) prepared by
      ultracentrifugation. In these LDL samples we could identify 46 oxidized molecular
      phosphatidylcholine species out of 99 possible candidates. 

PMID- 25874762
TI  - Identification and immune functional characterization of pigeon TLR7.
AB  - Toll-like receptor 7 (TLR7) is activated by single-stranded RNA and synthetic
      imidazoquinoline components, and induces interferon production. In this study, we
      cloned the TLR7 gene from King pigeon (Columba livia). The TLR7 open reading
      frame is 3144 bp and encodes a 1047-amino acid protein, consisting of a canonical
      TLR composition with 15 leucine-rich repeats (LRRs). Amino acid-inserting
      modifications were found at position 15 of LRR2, LRR11, LRR13, and LRR14 and
      position 10 of LRR10. The tissue distribution of pigeon TLR7 suggests that immune
      associated tissues, especially the spleen and liver, have high TLR7 expression.
      HEK293T cells transfected with pigeon TLR7 plasmid responded to the agonist R848,
      indicating a functional TLR7 homolog. Following R848 stimulation of pigeon
      peripheral blood mononuclear cells, the levels of IFN-gamma, IL-6, IL-8, CCL5,
      and IL-10 mRNA, assessed using quantitative real-time PCR, were significantly up
      regulated. After Newcastle disease virus vaccine strain LaSota inoculation and
      agonist R848 injection, the level of TLR7 mRNA in the spleen of pigeons increased
      significantly in the R848-injected group, but decreased in the LaSota-inoculated
      group at three day post-infection (d.p.i.). The mRNA levels of inflammatory
      cytokines and chemokines were significantly upregulated in both LaSota-inoculated
      and R848-injected groups. Triggering pigeon TLR7 leads to robust up-regulation of
      inflammatory cytokines and chemokines, suggesting an important role in the innate
      immune response. 

PMID- 25874763
TI  - Production and evaluation of virus-like particles displaying immunogenic epitopes
      of porcine reproductive and respiratory syndrome virus (PRRSV).
AB  - Porcine reproductive and respiratory syndrome (PRRS) is the most significant
      infectious disease currently affecting the swine industry worldwide. Several
      inactivated and modified live vaccines (MLV) have been developed to curb PRRSV
      infections. However, the efficacy and safety of these vaccines are
      unsatisfactory, and hence, there is a strong demand for the development of new
      PRRS universal vaccines. Virus-like particle (VLP)-based vaccines are gaining
      increasing acceptance compared to subunit vaccines, as they present the antigens
      in a more veritable conformation and are readily recognized by the immune system.
      Hepatitis B virus core antigen (HBcAg) has been successfully used as a carrier
      for more than 100 viral sequences. In this study, hybrid HBcAg VLPs were
      generated by fusion of the conserved protective epitopes of PRRSV and expressed
      in E. coli. An optimized purification protocol was developed to obtain hybrid
      HBcAg VLP protein from the inclusion bodies. This hybrid HBcAg VLP protein self
      assembled to 23-nm VLPs that were shown to block virus infection of susceptible
      cells when tested on MARC 145 cells. Together with the safety of non-infectious
      and non-replicable VLPs and the low cost of production through E. coli
      fermentation, this hybrid VLP could be a promising vaccine candidate for PRRS. 

PMID- 25874764
TI  - Insect-inspired navigation algorithm for an aerial agent using satellite imagery.
AB  - Humans have long marveled at the ability of animals to navigate swiftly,
      accurately, and across long distances. Many mechanisms have been proposed for how
      animals acquire, store, and retrace learned routes, yet many of these hypotheses
      appear incongruent with behavioral observations and the animals' neural
      constraints. The "Navigation by Scene Familiarity Hypothesis" proposed originally
      for insect navigation offers an elegantly simple solution for retracing
      previously experienced routes without the need for complex neural architectures
      and memory retrieval mechanisms. This hypothesis proposes that an animal can
      return to a target location by simply moving toward the most familiar scene at
      any given point. Proof of concept simulations have used computer-generated ant's
      eye views of the world, but here we test the ability of scene familiarity
      algorithms to navigate training routes across satellite images extracted from
      Google Maps. We find that Google satellite images are so rich in visual
      information that familiarity algorithms can be used to retrace even tortuous
      routes with low-resolution sensors. We discuss the implications of these findings
      not only for animal navigation but also for the potential development of visual
      augmentation systems and robot guidance algorithms. 

PMID- 25874765
TI  - Commentary on "anatomy of the surface layer of superficial fascia around the
      nipple-areola complex".

PMID- 25874766
TI  - The gut microbiota composition in dichorionic triplet sets suggests a role for
      host genetic factors.
AB  - Monozygotic and dizygotic twin studies investigating the relative roles of host
      genetics and environmental factors in shaping gut microbiota composition have
      produced conflicting results. In this study, we investigated the gut microbiota
      composition of a healthy dichorionic triplet set. The dichorionic triplet set
      contained a pair of monozygotic twins and a fraternal sibling, with similar pre-
      and post-natal environmental conditions including feeding regime. V4 16S rRNA and
      rpoB amplicon pyrosequencing was employed to investigate microbiota composition,
      and the species and strain diversity of the culturable bifidobacterial population
      was also examined. At month 1, the monozygotic pair shared a similar microbiota
      distinct to the fraternal sibling. By month 12 however, the profile was more
      uniform between the three infants. Principal coordinate analysis (PCoA) of the
      microbiota composition revealed strong clustering of the monozygotic pair at
      month 1 and a separation of the fraternal infant. At months 2 and 3 the
      phylogenetic distance between the monozygotic pair and the fraternal sibling has
      greatly reduced and by month 12 the monozygotic pair no longer clustered
      separately from the fraternal infant. Pulse field gel electrophoresis (PFGE)
      analysis of the bifidobacterial population revealed a lack of strain diversity,
      with identical strains identified in all three infants at month 1 and 12. The
      microbiota of two antibiotic-treated dichorionic triplet sets was also
      investigated. Not surprisingly, in both triplet sets early life antibiotic
      administration appeared to be a major determinant of microbiota composition at
      month 1, irrespective of zygosity. By month 12, early antibiotic administration
      appeared to no longer exert such a strong influence on gut microbiota
      composition. We hypothesize that initially host genetics play a significant role
      in the composition of an individual's gut microbiota, unless an antibiotic
      intervention is given, but by month 12 environmental factors are the major
      determinant. 

PMID- 25874768
TI  - Using support vector machine ensembles for target audience classification on
      Twitter.
AB  - The vast amount and diversity of the content shared on social media can pose a
      challenge for any business wanting to use it to identify potential customers. In
      this paper, our aim is to investigate the use of both unsupervised and supervised
      learning methods for target audience classification on Twitter with minimal
      annotation efforts. Topic domains were automatically discovered from contents
      shared by followers of an account owner using Twitter Latent Dirichlet Allocation
      (LDA). A Support Vector Machine (SVM) ensemble was then trained using contents
      from different account owners of the various topic domains identified by Twitter
      LDA. Experimental results show that the methods presented are able to
      successfully identify a target audience with high accuracy. In addition, we show
      that using a statistical inference approach such as bootstrapping in over
      sampling, instead of using random sampling, to construct training datasets can
      achieve a better classifier in an SVM ensemble. We conclude that such an ensemble
      system can take advantage of data diversity, which enables real-world
      applications for differentiating prospective customers from the general audience,
      leading to business advantage in the crowded social media space. 

PMID- 25874767
TI  - Analyses of the complete genome and gene expression of chloroplast of sweet
      potato [Ipomoea batata].
AB  - Sweet potato [Ipomoea batatas (L.) Lam] ranks among the top seven most important
      food crops cultivated worldwide and is hexaploid plant (2n=6x=90) in the
      Convolvulaceae family with a genome size between 2,200 to 3,000 Mb. The genomic
      resources for this crop are deficient due to its complicated genetic structure.
      Here, we report the complete nucleotide sequence of the chloroplast (cp) genome
      of sweet potato, which is a circular molecule of 161,303 bp in the typical
      quadripartite structure with large (LSC) and small (SSC) single-copy regions
      separated by a pair of inverted repeats (IRs). The chloroplast DNA contains a
      total of 145 genes, including 94 protein-encoding genes of which there are 72
      single-copy and 11 double-copy genes. The organization and structure of the
      chloroplast genome (gene content and order, IR expansion/contraction, random
      repeating sequences, structural rearrangement) of sweet potato were compared with
      those of Ipomoea (L.) species and some basal important angiosperms, respectively.
      Some boundary gene-flow and gene gain-and-loss events were identified at intra-
      and inter-species levels. In addition, by comparing with the transcriptome
      sequences of sweet potato, the RNA editing events and differential expressions of
      the chloroplast functional-genes were detected. Moreover, phylogenetic analysis
      was conducted based on 77 protein-coding genes from 33 taxa and the result may
      contribute to a better understanding of the evolution progress of the genus
      Ipomoea (L.), including phylogenetic relationships, intraspecific differentiation
      and interspecific introgression. 

PMID- 25874769
TI  - Erythropoietin Receptor Antagonist Suppressed Ectopic Hemoglobin Synthesis in
      Xenografts of HeLa Cells to Promote Their Destruction.
AB  - The aim of this study is to explore a cause-oriented therapy for patients with
      uterine cervical cancer that expresses erythropoietin (Epo) and its receptor
      (EpoR). Epo, by binding to EpoR, stimulates the proliferation and differentiation
      of erythroid progenitor cells into hemoglobin-containing red blood cells. In this
      study, we report that the HeLa cells in the xenografts expressed epsilon, gamma,
      and alpha globins as well as myoglobin (Mb) to produce tetrameric alpha2epsilon2
      and alpha2gamma2 and monomeric Mb, most of which were significantly suppressed
      with an EpoR antagonist EMP9. Western blotting revealed that the EMP9 treatment
      inhibited the AKT-pAKT, MAPKs-pMAPKs, and STAT5-pSTAT5 signaling pathways.
      Moreover, the treatment induced apoptosis and suppression of the growth and
      inhibited the survival through disruption of the harmonized hemoprotein syntheses
      in the tumor cells concomitant with destruction of vascular nets in the
      xenografts. Furthermore, macrophages and natural killer (NK) cells with intense
      HIF-1alpha expression recruited significantly more in the degenerating foci of
      the xenografts. These findings were associated with the enhanced expressions of
      nNOS in the tumor cells and iNOS in macrophages and NK cells in the tumor sites.
      The treated tumor cells exhibited a substantial number of perforations on the
      cell surface, which indicates that the tumors were damaged by both the nNOS
      induced nitric oxide (NO) production in the tumor cells as well as the iNOS
      induced NO production in the innate immune cells. Taken together, these data
      suggest that HeLa cells constitutively acquire epsilon, gamma and Mb synthetic
      capacity for their survival. Therefore, EMP9 treatment might be a cause-oriented
      and effective therapy for patients with squamous cell carcinoma of the uterine
      cervix. 

PMID- 25874770
TI  - Renal type a intercalated cells contain albumin in organelles with aldosterone
      regulated abundance.
AB  - Albumin has been identified in preparations of renal distal tubules and
      collecting ducts by mass spectrometry. This study aimed to establish whether
      albumin was a contaminant in those studies or actually present in the tubular
      cells, and if so, identify the albumin containing cells and commence exploration
      of the origin of the intracellular albumin. In addition to the expected proximal
      tubular albumin immunoreactivity, albumin was localized to mouse renal type-A
      intercalated cells and cells in the interstitium by three anti-albumin
      antibodies. Albumin did not colocalize with markers for early endosomes (EEA1),
      late endosomes/lysosomes (cathepsin D) or recycling endosomes (Rab11). Immuno
      gold electron microscopy confirmed the presence of albumin-containing large
      spherical membrane associated bodies in the basal parts of intercalated cells.
      Message for albumin was detected in mouse renal cortex as well as in a wide
      variety of other tissues by RT-PCR, but was absent from isolated connecting
      tubules and cortical collecting ducts. Wild type I MDCK cells showed robust
      uptake of fluorescein-albumin from the basolateral side but not from the apical
      side when grown on permeable support. Only a subset of cells with low peanut
      agglutinin binding took up albumin. Albumin-aldosterone conjugates were also
      internalized from the basolateral side by MDCK cells. Aldosterone administration
      for 24 and 48 hours decreased albumin abundance in connecting tubules and
      cortical collecting ducts from mouse kidneys. We suggest that albumin is produced
      within the renal interstitium and taken up from the basolateral side by type-A
      intercalated cells by clathrin and dynamin independent pathways and speculate
      that the protein might act as a carrier of less water-soluble substances across
      the renal interstitium from the capillaries to the tubular cells. 

PMID- 25874771
TI  - Combination of low calcium with Y-27632 rock inhibitor increases the
      proliferative capacity, expansion potential and lifespan of primary human
      keratinocytes while retaining their capacity to differentiate into stratified
      epidermis in a 3D skin model.
AB  - Human keratinocytes are difficult to isolate and have a limited lifespan.
      Traditionally, immortalised keratinocyte cell lines are used in vitro due to
      their ability to bypass senescence and survive indefinitely. However these cells
      do not fully retain their ability to differentiate in vitro and they are unable
      to form a normal stratum corneum in organotypic culture. Here we aimed to
      generate a pool of phenotypically similar keratinocytes from human donors that
      could be used in monolayer culture, without a fibroblast feeder layer, and in 3D
      human skin equivalent models. Primary human neonatal epidermal keratinocytes
      (HEKn) were cultured in low calcium, (0.07 mM) media, +/-10 MUM Y-27632 ROCK
      inhibitor (HEKn-CaY). mRNA and protein was extracted and expression of
      differentiation markers Keratin 14 (K14), Keratin 10 (K10) and Involucrin (Inv)
      assessed by qRT-PCR and Western blotting. The differentiation potential of the
      HEKn-CaY cultures was assessed by increasing calcium levels and removing the Y
      27632 for 72 hrs prior to assessment of K14, K10 and Inv. The ability of the HEKn
      CaY, to form a stratified epithelium was assessed using a human skin equivalent
      (HSE) model in the absence of Y-27632. Increased proliferative capacity,
      expansion potential and lifespan of HEKn was observed with the combination of low
      calcium and 10 MUM ROCK inhibitor Y-27632. The removal of Y-27632 and the
      addition of high calcium to induce differentiation allowed the cells to behave as
      primary keratinocytes even after extended serial passaging. Prolonged lifespan
      HEK-CaYs were capable of forming an organised stratified epidermis in 3D HSE
      cultures, demonstrating their ability to fully stratify and retain their
      original, primary characteristics. In conclusion, the use of 0.07 mM Calcium and
      10 MUM Y-27632 in HEKn monocultures provides the opportunity to culture primary
      human keratinocytes without a cell feeder layer for extended periods of culture
      whilst retaining their ability to differentiate and form a stratified epithelium.

PMID- 25874772
TI  - Deregulation between miR-29b/c and DNMT3A is associated with epigenetic silencing
      of the CDH1 gene, affecting cell migration and invasion in gastric cancer.
AB  - The de-regulation of the miR-29 family and DNA methyltransferase 3A (DNMT3A) is
      associated with gastric cancer (GC). While increasing evidence indicates miR
      29b/c could regulate DNA methylation by targeting DNMT3A, it is currently unknown
      if epigenetic silencing of miR-29b/c via promoter hypermethylation in GC is
      caused by abnormal expression of DNMT3A. Thus, we aimed to evaluate whether cross
      talk regulation exists between miR-29b/c and DNMT3A and whether it is associated
      with a malignant phenotype in GC. First, wound healing and Transwell assays
      revealed that miR-29b/c suppresses tumor metastasis in GC. A luciferase reporter
      assay demonstrated that DNMT3A is a direct target of miR-29b/c. We used bisulfite
      genomic sequencing to analyze the DNA methylation status of miR-29b/c. The
      percentage of methylated CpGs was significantly decreased in DNMT3A-depleted
      cells compared to the controls. Furthermore, the involvement of DNMT3A in
      promoting GC cell migration was associated with the promoter methylation-mediated
      repression of CDH1. In 50 paired clinical GC tissue specimens, decreased miR
      29b/c was significantly correlated with the degree of differentiation and
      invasion of the cells and was negatively correlated with DNMT3A expression.
      Together, our preliminary results suggest that the following process may be
      involved in GC tumorigenesis. miR-29b/c suppresses the downstream gene DNMT3A,
      and in turn, miR-29b/c is suppressed by DNMT3A in a DNA methylation-dependent
      manner. The de-regulation of both of miR-29b/c and DNMT3A leads to the epigenetic
      silencing of CDH1 and contributes to the metastasis phenotype in GC. This finding
      reveals that DNA methylation-associated silencing of miR-29b/c is critical for GC
      development and thus may be a therapeutic target. 

PMID- 25874775
TI  - Correction: Data-driven prediction and design of bZIP coiled-coil interactions.

PMID- 25874773
TI  - Examining the role of components of Slc11a1 (Nramp1) in the susceptibility of New
      Zealand sea lions (Phocarctos hookeri) to disease.
AB  - The New Zealand sea lion (NZSL, Phocarctos hookeri) is a Threatened marine mammal
      with a restricted distribution and a small, declining, population size. The
      species is susceptible to bacterial pathogens, having suffered three mass
      mortality events since 1998. Understanding the genetic factors linked to this
      susceptibility is important in mitigating population decline. The gene solute
      carrier family 11 member a1 (Slc11a1) plays an important role in mammalian
      resistance or susceptibility to a wide range of bacterial pathogens. At present,
      Slc11a1 has not been characterised in many taxa, and despite its known roles in
      mediating the effects of infectious disease agents, has not been examined as a
      candidate gene in susceptibility or resistance in any wild population of
      conservation concern. Here we examine components of Slc11a1 in NZSLs and
      identify: i) a polymorphic nucleotide in the promoter region; ii) putative shared
      transcription factor binding motifs between canids and NZSLs; and iii) a
      conserved polymorphic microsatellite in the first intron of Slc11a1, which
      together suggest conservation of Slc11a1 gene structure in otariids. At the
      promoter polymorphism, we demonstrate a shift away from normal allele frequency
      distributions and an increased likelihood of death from infectious causes with
      one allelic variant. While this increased likelihood is not statistically
      significant, lack of significance is potentially due to the complexity of genetic
      susceptibility to disease in wild populations. Our preliminary data highlight the
      potential significance of this gene in disease resistance in wild populations;
      further exploration of Slc11a1 will aid the understanding of susceptibility to
      infection in mammalian species of conservation significance. 

PMID- 25874774
TI  - Elevated serum microRNA levels associate with absence of high-grade prostate
      cancer in a retrospective cohort.
AB  - To reduce treatment of indolent prostate cancer (PCa), biomarkers are needed to
      improve identification of patients with a low-risk of having aggressive disease.
      Over-treatment of these patients occurs because of uncertainty in the
      aggressiveness of the entire tumor based on the biopsies, which do not accurately
      sample multifocal tumors. Circulating microRNAs (miRNAs) are stable serum markers
      and differential miRNA levels occur in men with PCa. The goal of this study was
      to identify circulating miRNAs that were associated with aggressive or indolent
      PCa. We measured circulating miRNAs in 150 patients prior to surgery and compared
      the miRNA levels to the pathology of the entire radical prostatectomy specimen.
      For this study we used an exceptionally well-characterized cohort of patients who
      had benign prostatic hyperplasia (BPH), low-grade or high-grade PCa. Low-grade
      was defined as patients with 100% Gleason grade 3 tumor as determined by step
      wise sectioning. High-grade PCa patients had 30-90% Gleason grade 4+5 in the
      tumor. BPH patients had at least two biopsies negative for PCa. Twenty one miRNAs
      were selected for analysis. The miRNAs were quantified by RT-qPCR and analyzed by
      logistic regression. High levels of 14 miRNAs were exclusively present in the
      serum from patients with low-grade PCa or BPH, compared to men with high-grade
      PCa who had consistently low levels. The expression levels of the 14 miRNAs were
      combined into a "miR Score" which had a negative predictive value (NPV) of 0.939
      to predict absence of high-grade PCa among PCa and BPH patients. Biochemical
      recurrence (BCR) was known for the PCa patients and a combined "miR Risk Score"
      accurately classified a subset of patients with low risk of BCR (NPV 0.941). In
      summary, measurement of serum miRNAs may have pre-surgical utility in combination
      with clinical risk calculators to identify patients with low risk of harboring
      aggressive PCa. 

PMID- 25874776
TI  - Temporal changes in glutaredoxin 1 and protein s-glutathionylation in allergic
      airway inflammation.
AB  - INTRODUCTION: Asthma is a chronic inflammatory disorder of the airways, involving
      oxidative stress. Upon oxidative stress, glutathione covalently binds to protein
      thiols to protect them against irreversible oxidation. This posttranslational
      modification, known as protein S-glutathionylation, can be reversed by
      glutaredoxin 1 (Glrx1) under physiological condition. Glrx1 is known to increase
      in the lung tissues of a murine model of allergic airway inflammation. However,
      the temporal relationship between levels of Glrx1, protein S-glutathionylation,
      and glutathione in the lungs with allergic airway inflammation is not clearly
      understood. METHODS: BALB/c mice received 3 aerosol challenges with ovalbumin
      (OVA) following sensitization to OVA. They were sacrificed at 6, 24, 48, or 72 h,
      or 8 days (5 mice per group), and the levels of Glrx1, protein S
      glutathionylation, glutathione, and 25 cytokines/chemokines were evaluated in
      bronchoalveolar lavage fluid (BALF) and/or lung tissue. RESULTS: Levels of Glrx1
      in BALF were significantly elevated in the OVA 6 h (final challenge) group
      compared to those in the control, with concurrent increases in protein S
      glutathionylation levels in the lungs, as well as total glutathione (reduced and
      oxidized) and oxidized glutathione in BALF. Protein S-glutathionylation levels
      were attenuated at 24 h, with significant increases in Glrx1 levels in lung
      tissues at 48 and 72 h. Glrx1 in alveolar macrophages was induced after 6 h.
      Glrx1 levels concomitantly increased with Th2/NF-kappaB-related cytokines and
      chemokines in BALF. CONCLUSIONS: The temporal relationships of Glrx1 with protein
      S-glutathionylation, glutathione, and cytokines/chemokines were observed as
      dynamic changes in lungs with allergic airway inflammation, suggesting that Glrx1
      and protein-SSG redox status may play important roles in the development of
      allergic airway inflammation.

PMID- 25874777
TI  - Effectiveness of meningococcal C conjugate vaccine in Salvador, Brazil: a case
      control study.
AB  - BACKGROUND: During a citywide epidemic of serogroup C meningococcal disease in
      Salvador in 2010, Brazil, the state government initiated mass vaccination
      targeting two age groups with high attack rates: individuals aged <5 years and 10
      24 years. More than 600,000 doses of meningococcal serogroup C conjugate vaccines
      were administered. We performed a case-control study to evaluate vaccine uptake,
      document vaccine effectiveness and identify reasons for non-vaccination. METHODS
      AND FINDINGS: Population-based surveillance identified patients with laboratory
      confirmed invasive meningococcal C (MenC) disease during 2010. Information on
      MenC vaccination was obtained from case patients and age-matched individuals from
      the same neighborhoods. MenC vaccine effectiveness was estimated based on the
      exact odds ratios obtained by conditional logistic regression analysis. Of 51
      laboratory-confirmed cases of serogroup C meningococcal disease among patients <5
      and 10-24 years of age 50 were included in the study and matched with 240
      controls. Overall case-fatality was 25%. MenC vaccine coverage among controls
      increased from 7.1% to 70.2% after initiation of the vaccination campaign. None
      of the 50 case patients but 70 (29.2%) of the 240 control individuals, including
      59 (70.2%) of 84 matched with cases from the period after MenC vaccination, had
      received at least one MenC vaccine dose. Overall effectiveness of MenC was 98%
      with a lower 95% exact confidence limit of 89%. CONCLUSIONS: MenC vaccines
      administered during the meningococcal epidemic were highly effective, suggesting
      that rapid vaccine uptake through campaigns contributed to control of
      meningococcal disease.

PMID- 25874778
TI  - The role of carnitine in the perinatal period.
AB  - Carnitine (2-hydroxy-4-trimethylammonium butyrate, vitamin BT) is a small
      hydrophilic molecule derived from protein-bound lysine, not degraded in the body
      but excreted via urine, bile and breast milk. Carnitine stimulates the catabolism
      of long-chain fatty acids (FAs), by transporting them to mitochondria for
      oxidation, and the intracellular decomposition of branched-chain ketoacids. It
      also helps to excrete toxic exogenous and nontoxic endogenous organic acids via
      urine. It further participates in the production of pulmonary surfactant,
      inhibits free radicals production and demonstrates other antioxidant properties.
      After delivery, infants dramatically increase energy demands for movement,
      growth, differentiation and maintenance of the body temperature that strongly
      depend on FAs oxidation which is facilitated by carnitine. At early stages of
      life, carnitine biosynthesis is less efficient than in adults and immature
      infants have less carnitine tissue reserves than term infants. Carnitine
      supplementation is recommended in newborns with aciduria, childhood epilepsy
      associated with valproate-induced hepatotoxicity, in kidney-associated syndromes,
      and premature infants receiving total parenteral nutrition. Concentrations of
      carnitine and acylcarnitines in neonatal blood have been postulated a useful tool
      for the diagnosis of type 1 diabetes, as well as the detection and monitoring of
      many inherited and acquired metabolic disorders. Taking into account the complex
      metabolic role of cellular FAs transporters, further studies are needed on
      indications and contraindications for carnitine supplementation in different
      clinical settings during early developmental period. 

PMID- 25874780
TI  - May the supplementation of lipid emulsion containing DHA in VLBW infants
      influence their psychological development evaluated at three years of age?
      Preliminary study.
AB  - OBJECTIVES: The aim of the study was to evaluate the possible influence of a
      lipid emulsion containing DHA (docosahexaenoic polyunsaturated fatty acid),
      parenterally administered from the first day of life, on the psychological
      development of 3-year-old children born with very low birth weight (VLBW). It was
      suspected that an increased amount of DHA in parenteral nutrition may be a
      variable that modifies the relation between other medical or social factors and
      their influence on the child's development. MATERIAL AND METHODS: Two groups of
      three-year-old children with calendar age ranging from 29 to 51 months (mean
      value--38 months) were tested. The children in the study group (n=23) were
      parenterally nourished during the first weeks of life with a lipid emulsion
      containing DHA. The patients in the control group (n=13) were fed with a lipid
      emulsion without DHA. RESULTS: Using the General Linear Model (GLM) with the
      analysis of interaction effects, it was found that the supplementation of the
      lipid emulsion containing DHA in parenteral nutrition from the first day of life
      beneficially influenced the relation between immaturity associated with the
      children's health status at birth and emotional development evaluated at three
      years of age. It also modified the relation between emotional and linguistic
      development. CONCLUSIONS: When administered after birth in prematurely born
      children, the lipid emulsion containing DHA may influence their development at
      the age of three years. It may either compensate the negative effects that
      immaturity associated with the health status at birth has on emotional
      development, or stimulate the language development in children whose emotional
      development is normal.

PMID- 25874779
TI  - Genetic epilepsies with febrile seizures plus: clinical spectrum of Polish
      patients with SCN1A mutation - preliminary report.
AB  - Diseases caused by mutations in SCN1A are currently named Genetic Epilepsies with
      Febrile Seizures Plus, and this term stands for expanded spectrum of syndrome
      previously called as GEFS+ (Generalized Epilepsy with Febrile Seizures Plus).
      SCN1A is the uniquely identified gene directly linked to specific type of
      epilepsy, and its testing has been included in the screening processes. THE AIM:
      To diagnose and describe epileptic syndromes caused by SCN1A mutations. MATERIAL
      AND METHODS: 203 patients were included in the screening process with suspected
      SCN1A mutation, based on clinical features and family history. Study group was
      selected based on inclusion and exclusion criteria and then preliminary epilepsy
      diagnosis was verified using ILAE classification. Molecular testing to screen
      SCN1A mutations was performed in the study group. RESULTS: Mutations were
      detected in 57 cases. Majority of patients (50 cases - 87.5%) suffered from
      Dravet syndrome, 8.8% (5 cases) were diagnosed as GEFS+, 3% as vaccines
      encephalopathy and Panayotopoulous syndrome. Mutations were not detected in
      children with isolated febrile seizures, family febrile seizures nor in patients
      with myoclonic - astatic epilepsy. CONCLUSIONS: Frequency of mutations in SCN1A
      in Dravet syndrome and GEFS+ in Polish populations are similar to other
      countries. Diagnostic clinical criteria are currently insufficient to draw
      precise diagnosis. There is a strong need to establish clinical criteria for
      molecular testing and this topic will be investigated in the future.

PMID- 25874781
TI  - Maternal bond with cardiosurgically treated infant. Qualitative analysis of
      mothers' narratives.
AB  - The aim of this work is to describe the experience of being a mother by women who
      together with their children stay on the ward after cardiac surgical correction
      of congenital heart defects. The research material consisted of the narratives of
      mothers whose children were born with a heart defect and surgically treated. Four
      women aged 21-30 years were participants of this study. The age of the subjects'
      children ranged from 5 weeks to 1 year and three months. The heart defects with
      which the children were born were hypoplastic left heart syndrome (HLHS ) or
      atrioventricular canal defect. The research was carried out using the narrative
      interview. Qualitative analysis was carried out according to the rules of
      thematic analysis. The results of the research confirm that cardiac treatment can
      have a significant impact on maternal care patterns and the mother-infant bonding
      process. Intermittent contact with an infant can lead to loss of control over
      what happens to the child and the loss of a sense of competence to care for him.
      Medical staff face the challenge of supporting the parents of hospitalized
      children in the process of building relationships with a sick infant. The actions
      of doctors and nurses to enable parents to care for a baby can help foster their
      sense of competence and responsibility. 

PMID- 25874782
TI  - Cephalic index in the evaluation of surgical treatment of children with sagittal
      synostosis. Preliminary report.
AB  - AIM OF THE STUDY: To analyze changes of the cephalic index (CI) values in
      patients with sagittal synostosis operated on in the Department of Surgery of
      Children and Adolescents of the Institute of Mother and Child in Warsaw. MATERIAL
      AND METHODS: The study group consisted of 14 consecutive cases (11 boys and 3
      girls). In 8 patients younger than 3 months of age (1st subgroup) the modified
      reversed-pi technique (craniotomy in the shape of the reversed Greek pi letter)
      was utilized. In 6 older infants and in patients with severe head deformity - the
      radical cranial vault reconstructions were performed (2nd subgroup). The
      statistical analysis of the preoperative (preop) and postoperative (postop)
      cephalic index (CI) values was done. RESULTS: For the entire study group the
      preop CI values ranged from 61 to 77 (mean 68.14, median 68.5) and postop CIs
      from 73 to 89 (mean 77.64, median 76). In the 1st subgroup the preop CIs ranged
      from 63 to 77 (mean 69.625, median 69) whereas the postop CIs from 69 to 89 (mean
      78.125, median 76.5). In the 2nd subgroup the preop CI values ranged from 61 to
      72 (mean 66.1667, median 66) and postop from 73 to 81 (mean 77, median 77). All
      the differences were statistically significant. CONCLUSION: The values of
      cephalic index increased after both types of procedures. It signifies the
      correction of dolichocephaly in both subgroups of the patients. However, because
      of the small number of operated children, further studies are necessary.

PMID- 25874783
TI  - Assessment of connection between the bite plane and body posture in children and
      teenagers.
AB  - AIM: Attempt to compare the occlusion condition in groups of children with
      different body posture. MATERIAL AND METHODS: 336 children aged from 8 to 14
      years were investigated. The subjects were selected in orthodontic clinics (237
      children) and at schools (98 children). All participants were divided into groups
      with different body posture according to Kasperczyk's point method. The
      comparison of the occlusion quality was performed with the use of a scale
      developed by Emmerich-Poplatek. RESULTS: The studied group comprised following
      number of persons: 12 (3.56%) with no malocclusion, 37 (10.98%) with mild, 162
      (48.37%) with moderate and 124 (37.09%) with severe malocclusion. In relation to
      the body posture, 52.67% of the participants had correct posture, 45.53 % had a
      faulty posture of mild degree and 1.78% of severe degree. A considerable
      differentiation of the occlusion condition was discovered within the three
      groups. In view of a small number of participants with a faulty posture of
      considerable degree (n=6) the comparative analysis of the occlusion condition was
      performed between the group with a correct body posture and group with faulty
      posture (created by combining group 2 and 3). The result of the analysis suggests
      a significant differentiation of the occlusion condition between the groups
      mentioned above (p<0.01). CONCLUSION: Children with faulty postures present more
      intense malocclusions than children with a correct body posture. Results of this
      type suggest the need for interdisciplinary look at people with malocclusions
      whose therapy should involve body posture correction.

PMID- 25874784
TI  - Usefulness of lower-dose computed tomography urography with iterative
      reconstruction technique in diagnosis of congenital anomalies in urinary tract in
      children.
AB  - Introduction of iterative reconstruction technique in modern computed tomography
      allowed to reduce the radiation dose and to extend indications for computed
      tomography urography in children. We describe the case of boy with congenital
      anomalies in urinary tract including bilateral double collecting system,
      dilatation of double collecting system in the right kidney and dilatation of
      lower pelvis in left kidney and bilateral dilatation of ureters. Anomalies were
      detected in prenatal and then confirmed in postnatal ultrasonography. Voiding
      cystourethrograhy, which was performed on the 4th day of life revealed grade IV
      vesicoureteral reflux to the lower part of double collecting system in the right
      kidney and grade V vesicoureteral reflux to the left kidney. In cystoscopy
      posterior urethral valves were excluded and presence of double ureters was
      confirmed. Dynamic scintigraphy (99mTc-EC) detected impaired parenchymal
      secretory function in the lower pole of left kidney. The patient was qualified
      for surgical treatment including left lower heminephoureterectomy. Before surgery
      procedure computed tomography urography was performed and revealed congenital
      anomalies in urinary tract: bilateral double collecting system, bilateral
      hydronephrosis of the lower part of kidneys, dilatation of ureters associated
      with high grade of vesicoureteral refluxes, narrow cortex of left kidney.
      Computed tomography urography with iterative reconstruction techniques enables
      precise visualization of urinary tracts with reduced radiation dose. It replaces
      conventional X-ray urography because of much better visualization of urinary
      tracts with comparable or even lower radiation dose. 

PMID- 25874785
TI  - [Diagnosis and treatment of urinary tract infections in children on the basis of
      various recommendations].
AB  - Urinary tract infections (UTIs) are the most common bacterial diseases of
      childhood. Early diagnosis infection is extremely important because it is often
      the first clinical manifestation of a serious pathology of the urinary tract. In
      the case of coexistence of urinary tract defects it can lead to end-stage renal
      failure and the need for implementation of renal replacement therapy. In children
      with a history of traveling at least one episode of UTI is the most common
      drawback of vesicoureteral reflux. Until recently, the predominant view that
      chronic pharmacological used antimicrobial prophylaxis and early treatment will
      allow the implementation of the inhibition of progression of chronic kidney
      disease (CKD). This was based on the assumption that there is a causal
      relationship between vesicoureteral reflux, especially a high grade (III-V), and
      recurrent UTIs, which was regarded as the immediate cause of kidney damage and
      the development of the so-called reflux nephropathy. In the last decade we
      observe a significant change of views on the root causes damage to the renal
      parenchyma, and the consequences of previous UTI pathogenesis vesicoureteral
      reflux. For this reason, in many countries modified existing recommendations for
      diagnostic and therapeutic agent in children with urinary tract infections. 

PMID- 25874786
TI  - [The etiology of urinary tract infections and antimicrobial susceptibility: study
      based on children hospitalized in 2012].
AB  - AIM: Assessment of the etiology of urinary tract infections and pathogen drug
      sensitivity in hospitalized children. MATERIALS AND METHODS: We analyzed 156
      medical records of patients admitted to the Clinical Department of Pediatrics,
      Bielanski Hospital in Warsaw in 2012, with a suspected UTI. Positive urine
      culture results were found in 113 (72.4%) children (68; 60.2% of girls and 45;
      39.8% of boys), aged from 2 months to 17.9 years (the average age was 2 years and
      3 months). RESULTS: E. coli was the most frequent isolated pathogen - 92.0% of
      patients (104/113). The greatest sensitivity of pathogens showed to
      cephalosporins of the second and third generation (80.5-90.3%). The sensitivity
      to amoxicillin with clavulanic acid was 71.7% and 41.6% for ampicillin. The
      length of hospital stay and treatment ranged from 2 to 16 days (average 8.6
      days). In 60.2% (68/113) of patients were treated with second cephalosporin, in
      17.7% (20/113) with third generation cephalosporins. Only 11.5% of them (13/113)
      received amoxicillin with clavulanic acid. Before the treatment, 69.9% (79/113)
      of children had a fever from 38 up to 41,7oC, and the fever persisted for the
      average of 2.5 days (1-8 days). We found significantly higher levels of CRP in
      children aged between 2-4 in comparison to other age groups (p= 0.0290). In 44.2%
      (50/113) of children the cystourethrography was performed and in 22% (11/50)
      cases we recognized a unilateral or bilateral vesicoureteral-ureter of a I to IV
      degree, on one or both sides. CONCLUSION: The most common etiological agent of
      UTIs in children remains E. coli. The sensitivity of urinary pathogens to the
      commonly used antibiotics is still high, however, finds a large percentage of
      strains resistant to ampicillin and to amoxicillin with clavulanic acid. The
      antibiotic recommended for empiric therapy of UTIs in children should be
      cephalosporins, if there is such a possibility, the treatment should be based on
      drug sensitivity tests of the organisms grown. Because of the relatively long
      hospitalization of children with UTIs and the possibility of hospital
      complications, sequential treatment should also be considered sequential.

PMID- 25874787
TI  - [The role of early-life metabolic programming in the pathogenesis of lifestyle
      diseases].
AB  - In recent years, a blooming period of genomics brings a window of opportunity to
      assess predispositions to some diseases in individuals, even before the first
      symptoms appear. However, a risk of becoming ill is more complex, as the gene
      expression is modified by epigenetic and environmental factors. Fetal development
      and first months of life are periods of dynamic growth and significant
      sensitivity to external factors. According to the theory of early-life metabolic
      programming, adaptive changes in these stages have lasting health effects. Among
      many environmental factors, the youngest children's diet plays an important role.
      Breastfeeding of newborns and infants is an essential part of lifestyle diseases
      prevention. Constantly increasing number of reports link natural nutrition of the
      youngest children with less risk of obesity, hypertension, dyslipidemia and
      insulin resistance in future life. However, further long-term studies taking into
      account number of bias factors, explaining protective mechanisms of human milk,
      are needed. 

PMID- 25874788
TI  - [Malignant hyperthermia - problem in dental surgery. An introductory report].
AB  - Malignant hyperthermia is a genetic defect of uncontrolled hypermetabolic
      skeletal muscle response to anesthetic triggering drugs. Some congenital
      myopathies are regarded as risk increasing factors. The use of volatile
      anaesthetics or suxamethonium (succinylcholine) in patients who are predisposed
      to malignant hyperthermia leads to an increase in Ca2+ release from sarcoplasmic
      reticulum, which in turn causes a set of biochemical and clinical symptoms, which
      can be a cause of death, if dantrolene is not administered adequately. The aim of
      the study was to draw attention to the problem of malignant hyperthermia, which
      is hardly ever described in Polish literature, and requires the necessity of
      intensifying the cooperation between the dentist and specialists from other
      medical fields. The origin of the article was a case of congenital myopathy with
      recognized malignant hyperthermia in an 18-year-old patient, in whom surgical
      extraction of teeth was indicated. The course of diagnostics and treatment showed
      once more that contemporary medicine is in need of holistic approach, and in
      consequence, promising and effective cooperation of many specialists. 

PMID- 25874789
TI  - [Prolonged leucopenia in asymptomatic children].
AB  - INTRODUCTION: The term leucopenia is still a challenge for clinicists in cases of
      unknown reasons. There are two main groups of leucopenia: 1. Severe, chronic
      leucopenia (cyclic, inborn, and idiopathic); 2. Acquired or secondary (reasons:
      some drugs, infections, viral mainly, autoimmune diseases, haematological
      abnormalities, neoplasms, hiperspleenism and metabolic diseases). The aim of this
      investigation was an analysis of asymptomatic, lasting over three months
      leucopenia myelograms of childhood. MATERIAL AND METHODS: 21 children (6 girls
      and 15 boys, aged 10-17 years, mean 13.6, median 12 years) were analysed. The
      children were referred to our clinic by family physicians to investigate the
      reason of asymptomatic, lasting over three months leucopenia. These children are
      still under our observation from one till four years. Despite the fact of lasting
      over three months leucopenia, the general condition of the patients is good. In
      all the patients the myelogram analysis was performed after May-Grumwald-Giemsa
      dying, three slides of one hundred cells were counted. Statistical analysis was
      made using STATISTICA (Stat Soft Polska) programme. RESULTS: Mean number of
      leucocytes was 3.06x109/ l (median 2.75x109/l, values from 2.46x109/l to
      3.53x109/l), mean number of neutrocytes was 1.15x109/l (median 1.07 x 109/l,
      values from 0.62x109/l to 1470x109/l). Hemoglobin concentration and platelets
      number were normal. Mean number of marrow cells were within references. However
      mean number of myelocytes, metamyelocytes, bands and eosynophils were lower than
      mean number of general population marrow cells (p<0.05). Mean values of
      myeloblasts, neutrophils, and monocytes were statistically higher than in general
      population (p<0.05). CONCLUSIONS: 1. Hypothesis of obtained differencess in numer
      of marrow cells would need to be investigated in broad population of patients. 2.
      Considering that three children presented with positive familial leucopenia
      history (in one of them grandmother, in two anothers fathers) genetic
      predisposition can be expected.

PMID- 25874790
TI  - [Selected family socio-economic factors as predictors of peer violence among
      school children in Poland].
AB  - AIM: Analyses concerning peer violence among girls and boys aged 13-17 years, in
      the context of socio- -economic characteristics of the family: family structure,
      parental employment status and perceived family wealth. MATERIAL AND METHODS:
      Preliminary data from the recent HBSC studies conducted in 12 voivodeships in
      Poland in 2013 was used. The analyzes concerned 2300 students aged 13-17 years
      (45% boys) and focused on the following types of violence: being a perpetrator
      and a victim of bullying, participation in fights and cyberbullying. Chi-square
      test analysis and multivariate logistic regression models were used. RESULTS:
      Significantly more boys than girls experienced bullying (28% vs. 22%) and was
      perpetrators of violence in the school (39% vs. 25%). The youth from single
      parent families significantly more often than students from two-parent families,
      participated in fights and was the perpetrators of violence in the school. Being
      a perpetrator and a victim of violence concerned mostly students from poor
      families and boys, whose father was unemployed. The following risk factors was
      identified- among boys: low economic status of the family (victims of bullying)
      and single-parent family (victims of cyberbullying), father's unemployment (the
      perpetrator of bullying) and age 13-14 years (victims and perpetrators of
      bullying, participation in fights) and among girls: low economic status of the
      family (cyberbullying), mother's unemployment and age 13-14 years (victims of
      violence). CONCLUSIONS: The family socio-economic factors, gender and age
      determine the type and the prevalence of peer violence. Low economic status of
      the family and single-parent family increases the risk of experiencing violence.
      For the prevention of bullying the educational role of the father and his
      commitment to family budget are important.

PMID- 25874791
TI  - The etiology and clinical manifestation of erythema nodosum in hospitalized
      children - analysis of 12 cases. Preliminary report.
AB  - AIM: To analyse etiologic factors and the clinical course of erythema nodosum in
      hospitalized children. MATERIAL AND METHODS: A retrospective study of 12 children
      and young people (7 girls and 5 boys) admitted to the Paediatric Clinic in Zabrze
      with erythema nodosum was performed from January 2004 to February 2014. The
      patients' mean age on admission was 11.9 years (2-16). RESULTS: In ten of the 12
      patients elevated CRP was identified - from 10 mg/L to 131.5 mg/L, which is proof
      of an ongoing inflammatory process. Only two patients had a CRP level below 5
      mg/L. Three of the 12 patients were diagnosed with Crohn's Disease, one with
      diarrhoea (Salmonella was cultured and antigen Rotavirus was found), one with
      arthritis, one with bilateral cervical lymphadenopathy, three with Streptococcal
      infection, two had elevated anti-streptolysin O level (ASO). CONCLUSION: The
      present research may confirm the hypothesis that EN could be the first sign of
      systemic diseases. However, it requires further studies because of the limited
      number of patients.

PMID- 25874793
TI  - Correction: Relationship between tobacco, IcagA and vacA i1 virulence factors and
      bacterial load in patients infected by Helicobacter pylori.

PMID- 25874792
TI  - Serine 26 in the PomB subunit of the flagellar motor is essential for
      hypermotility of Vibrio cholerae.
AB  - Vibrio cholerae is motile by means of its single polar flagellum which is driven
      by the sodium-motive force. In the motor driving rotation of the flagellar
      filament, a stator complex consisting of subunits PomA and PomB converts the
      electrochemical sodium ion gradient into torque. Charged or polar residues within
      the membrane part of PomB could act as ligands for Na+, or stabilize a hydrogen
      bond network by interacting with water within the putative channel between PomA
      and PomB. By analyzing a large data set of individual tracks of swimming cells,
      we show that S26 located within the transmembrane helix of PomB is required to
      promote very fast swimming of V. cholerae. Loss of hypermotility was observed
      with the S26T variant of PomB at pH 7.0, but fast swimming was restored by
      decreasing the H+ concentration of the external medium. Our study identifies S26
      as a second important residue besides D23 in the PomB channel. It is proposed
      that S26, together with D23 located in close proximity, is important to perturb
      the hydration shell of Na+ before its passage through a constriction within the
      stator channel. 

PMID- 25874794
TI  - Increased risks of mortality and atherosclerotic complications in incident
      hemodialysis patients subsequently with bone fractures: a nationwide case-matched
      cohort study.
AB  - BACKGROUND: Hemodialysis (HD) patients with bone fractures have an increased risk
      for death. However, the risks for mortality and atherosclerotic complications in
      incident HD patients subsequently with bone fractures are unknown. METHODS: Data
      derived from the Taiwan National Health Institute Research Database between
      January 1997 and December 2008 was analyzed. The enrolled patients included 3,008
      incident HD patients subsequently with a single long bone fracture (LB Fx) and
      2,070 incident HD patients subsequently with a single non-long bone fracture (NLB
      Fx). These patients were matched (1:5 ratio) for age, sex, and same duration of
      HD with incident HD patients who had no fractures and outcomes were measured over
      a 3-year follow-up. RESULTS: After demographic and co-morbidity adjustment, LB Fx
      increased the risk for overall mortality (HR = 1.59, p < 0.001) and stroke (HR =
      1.09, p = 0.028) in incident HD patients. NLB Fx increased the risk for overall
      mortality (HR = 1.52, p < 0.001), stroke (HR = 1.19, p < 0.001), coronary artery
      disease (CAD), (HR = 1.13, p = 0.003), and peripheral arterial occlusive disease
      (PAOD), (HR = 1.41, p < 0.001) in incident HD patients. Moreover, incident
      patients subsequently with NLB Fx had significantly higher risks of CAD and PAOD
      than those subsequently with LB Fx. CONCLUSIONS: The rates of mortality and
      stroke were significantly higher in incident HD patients subsequently with bone
      fractures than in matched patients without bone fractures. Incident HD patients
      subsequently with NLB Fx had significantly higher risks of CAD and PAOD than
      those subsequently with LB Fx and without bone fractures. Thus, incident HD
      patients subsequently with bone fractures should be closely followed for a higher
      mortality and possible development of atherosclerotic complications.

PMID- 25874795
TI  - A specific association between facial disgust recognition and estradiol levels in
      naturally cycling women.
AB  - Subtle changes in social cognition are associated with naturalistic fluctuations
      in estrogens and progesterone over the course of the menstrual cycle. Using a
      dynamic emotion recognition task we aimed to provide a comprehensive description
      of the association between ovarian hormone levels and emotion recognition
      performance using a variety of performance metrics. Naturally cycling,
      psychiatrically healthy women attended a single experimental session during a
      follicular (days 7-13; n = 16), early luteal (days 15-19; n = 14) or late luteal
      phase (days 22-27; n = 14) of their menstrual cycle. Correct responses and
      reaction times to dynamic facial expressions were recorded and a two-high
      threshold analysis was used to assess discrimination and response bias. Salivary
      progesterone and estradiol were assayed and subjective measures of premenstrual
      symptoms, anxiety and positive and negative affect assessed. There was no
      interaction between cycle phase (follicular, early luteal, late luteal) and
      facial expression (sad, happy, fearful, angry, neutral and disgusted) on any of
      the recognition performance metrics. However, across the sample as a whole,
      progesterone levels were positively correlated with reaction times to a variety
      of facial expressions (anger, happiness, sadness and neutral expressions). In
      contrast, estradiol levels were specifically correlated with disgust processing
      on three performance indices (correct responses, response bias and
      discrimination). Premenstrual symptoms, anxiety and positive and negative affect
      were not associated with emotion recognition indices or hormone levels. The study
      highlights the role of naturalistic variations in ovarian hormone levels in
      modulating emotion recognition. In particular, progesterone seems to have a
      general slowing effect on facial expression processing. Our findings also provide
      the first behavioural evidence of a specific role for estrogens in the processing
      of disgust in humans. 

PMID- 25874797
TI  - WITHDRAWN: Acid reflux treatment for hoarseness.

PMID- 25874796
TI  - Skeletal muscle microRNA and messenger RNA profiling in cofilin-2 deficient mice
      reveals cell cycle dysregulation hindering muscle regeneration.
AB  - Congenital myopathies are rare skeletal muscle diseases presenting in early age
      with hypotonia and weakness often linked to a genetic defect. Mutations in the
      gene for cofilin-2 (CFL2) have been identified in several families as a cause of
      congenital myopathy with nemaline bodies and cores. Here we explore the global
      messenger and microRNA expression patterns in quadriceps muscle samples from
      cofillin-2-null mice and compare them with sibling-matched wild-type mice to
      determine the molecular pathways and mechanisms involved. Cell cycle processes
      are markedly dysregulated, with altered expression of genes involved in mitotic
      spindle formation, and evidence of loss of cell cycle checkpoint regulation.
      Importantly, alterations in cell cycle, apoptosis and proliferation pathways are
      present in both mRNA and miRNA expression patterns. Specifically, p21 transcript
      levels were increased, and the expression of p21 targets, such as cyclin D and
      cyclin E, was decreased. We therefore hypothesize that deficiency of cofilin-2 is
      associated with interruption of the cell cycle at several checkpoints, hindering
      muscle regeneration. Identification of these pathways is an important step
      towards developing appropriate therapies against various congenital myopathies. 

PMID- 25874798
TI  - Danger comes from all fronts: predator-dependent escape tactics of tungara frogs.
AB  - The escape response of an organism is generally its last line of defense against
      a predator. Because the effectiveness of an escape varies with the approach
      behaviour of the predator, it should be advantageous for prey to alter their
      escape trajectories depending on the mode of predator attack. To test this
      hypothesis we examined the escape responses of a single prey species, the ground
      dwelling tungara frog (Engystomops pustulosus), to disparate predators
      approaching from different spatial planes: a terrestrial predator (snake) and an
      aerial predator (bat). Tungara frogs showed consistently distinct escape
      responses when attacked by terrestrial versus aerial predators. The frogs fled
      away from the snake models (Median: 131 degrees ). In stark contrast, the frogs
      moved toward the bat models (Median: 27 degrees ); effectively undercutting the
      bat's flight path. Our results reveal that prey escape trajectories reflect the
      specificity of their predators' attacks. This study emphasizes the flexibility of
      strategies performed by prey to outcompete predators with diverse modes of
      attack. 

PMID- 25874800
TI  - Influence of Newtonian heating on three dimensional MHD flow of couple stress
      nanofluid with viscous dissipation and Joule heating.
AB  - The present exploration discusses the influence of Newtonian heating on the
      magnetohydrodynamic (MHD) three dimensional couple stress nanofluid past a
      stretching surface. Viscous dissipation and Joule heating effects are also
      considered. Moreover, the nanofluid model includes the combined effects of
      thermophoresis and Brownian motion. Using an appropriate transformation, the
      governing non linear partial differential equations are converted into nonlinear
      ordinary differential equations. Series solutions using Homotopy Analysis method
      (HAM) are computed. Plots are presented to portrait the arising parameters in the
      problem. It is seen that an increase in conjugate heating parameter results in
      considerable increase in the temperature profile of the stretching wall. Skin
      friction coefficient, local Nusselt and local Sherwood numbers tabulated and
      analyzed. Higher values of conjugate parameter, Thermophoresis parameter and
      Brownian motion parameter result in enhancement of temperature distribution. 

PMID- 25874799
TI  - Preferential targeting of Nav1.6 voltage-gated Na+ Channels to the axon initial
      segment during development.
AB  - During axonal maturation, voltage-gated sodium (Nav) channels accumulate at the
      axon initial segment (AIS) at high concentrations. This localization is necessary
      for the efficient initiation of action potentials. The mechanisms underlying
      channel trafficking to the AIS during axonal development have remained elusive
      due to a lack of Nav reagents suitable for high resolution imaging of channels
      located specifically on the cell surface. Using an optical pulse-chase approach
      in combination with a novel Nav1.6 construct containing an extracellular
      biotinylation domain we demonstrate that Nav1.6 channels are preferentially
      inserted into the AIS membrane during neuronal development via direct vesicular
      trafficking. Single-molecule tracking illustrates that axonal channels are
      immediately immobilized following delivery, while channels delivered to the soma
      are often mobile. Neither a Nav1.6 channel lacking the ankyrin-binding motif nor
      a chimeric Kv2.1 channel containing the Nav ankyrinG-binding domain show
      preferential AIS insertion. Together these data support a model where ankyrinG
      binding is required for preferential Nav1.6 insertion into the AIS plasma
      membrane. In contrast, ankyrinG-binding alone does not confer the preferential
      delivery of proteins to the AIS. 

PMID- 25874801
TI  - Identification of a novel Afipia species isolated from an Indian flying fox.
AB  - An old world fruit bat Pteropus giganteus, held in captivity and suffering from
      necrosis of its wing digits, failed to respond to antibiotic therapy and
      succumbed to the infection. Samples submitted to the National Centre for Foreign
      Animal Disease were tested for viral infection. Vero E6 cells exhibited minor but
      unique cytopathic effects on second blind passage, and full CPE by passage four.
      Utilizing an unbiased random amplification technique from cell culture
      supernatant, we identified a bacterium belonging to the Bradyrhizobiaceae.
      Purification of cell culture supernatant on TY media revealed a slow growing
      bacterial isolate. In this study using electron microscopy, 16S rRNA gene
      analysis and whole genome sequencing, we identify a novel bacterial species
      associated with the site of infection belonging to the genus Afipia. This genus
      of bacteria is very diverse, with only a limited number of species characterized.
      Afipia felis, previously described as the etiological agent to cause cat scratch
      disease, and Afipia septicemium, most recently shown to cause disease in humans,
      highlight the potential for members of this genus to form a branch of
      opportunistic pathogens within the Bradyrhizobiaceae. Increased utilization of
      next generation sequencing and genomics will aid in classifying additional
      members of this intriguing bacterial genera. 

PMID- 25874802
TI  - Comparative efficacy and tolerability of three treatments in old people with
      osteoporotic vertebral compression fracture: a network meta-analysis and
      systematic review.
AB  - PURPOSE: The question which kind of methods is most suitable for treating the old
      people for osteoporotic vertebral compression fracture is still discussed and
      pairwise meta-analyses cannot get hierarchies of these treatments. Our aim is to
      integrate the evidence to provide hierarchies of the comparative efficacy
      measured by the change of VAS (Visual Analogue Scale) and tolerability measured
      by incidence of new fractures and risk of all-cause discontinuation on three
      treatments (percutaneous vertebroplasty (PVP),balloon kyphoplasty (BK) and
      conservative treatment (CT)). METHODS: We performed a Bayesian-framework network
      meta-analysis of randomized controlled trials (RCTs) to compare three treatments
      for the old people with osteoporotic vertebral compression fracture. The eligible
      RCTs were identified by searching Amed, British Nursing Index, Embase, Pubmed,
      the Cochrane Central Register of Controlled Trials (CENTRAL), Google scholar,
      SIGLE, the National Technical Information Service, the National Research Register
      (UK) and the Current Controlled Trials databases. Data from three outcomes (e.g.
      VAS, risk of all-cause discontinuation and incidence of new fractures) were
      independently extracted by two authors. RESULTS: A total of five RCTs were
      finally included into this article. PVP and BK significantly decreased VAS when
      compared with CT. BK had a significantly lower risk of all-cause discontinuation
      contrast to CT. Three treatments (BK, PVP and CT) had no significant differences
      in the incidence of new fractures. CONCLUSIONS: PVP may be the best way to
      relieve pain, CT might lead to the lowest incidence of new fractures and BK might
      had the lowest risk of all-cause discontinuation in old people with osteoporotic
      vertebral compression fracture. More large-scale and longer duration of follow-up
      studies are needed.

PMID- 25874803
TI  - Rapid on-site sensing aflatoxin B1 in food and feed via a chromatographic time
      resolved fluoroimmunoassay.
AB  - Aflatoxin B1 poses grave threats to food and feed safety due to its strong
      carcinogenesis and toxicity, thus requiring ultrasensitive rapid on-site
      determination. Herein, a portable immunosensor based on chromatographic time
      resolved fluoroimmunoassay was developed for sensitive and on-site determination
      of aflatoxin B1 in food and feed samples. Chromatographic time-resolved
      fluoroimmunoassay offered a magnified positive signal and low signal-to-noise
      ratio in time-resolved mode due to the absence of noise interference caused by
      excitation light sources. Compared with the immunosensing performance in previous
      studies, this platform demonstrated a wider dynamic range of 0.2-60 MUg/kg, lower
      limit of detection from 0.06 to 0.12 ug/kg, and considerable recovery from 80.5%
      to 116.7% for different food and feed sample matrices. It was found to be little
      cross-reactivity with other aflatoxins (B2, G1, G2, and M1). In the case of
      determination of aflatoxin B1 in peanuts, corn, soy sauce, vegetable oil, and
      mouse feed, excellent agreement was found when compared with aflatoxin B1
      determination via the conversational high-performance liquid chromatography
      method. The chromatographic time-resolved fluoroimmunoassay affords a powerful
      alternative for rapid on-site determination of aflatoxin B1 and holds a promise
      for food safety in consideration of practical food safety and environmental
      monitoring. 

PMID- 25874804
TI  - The availability and consistency of dengue surveillance data provided online by
      the World Health Organization.
AB  - BACKGROUND: The use of high quality disease surveillance data has become
      increasingly important for public health action against new threats. In response,
      countries have developed a wide range of disease surveillance systems enabled by
      technological advancements. The heterogeneity and complexity of country data
      systems have caused a growing need for international organizations such as the
      World Health Organization (WHO) to coordinate the standardization, integration,
      and dissemination of country disease data at the global level for research and
      policy. The availability and consistency of currently available disease
      surveillance data at the global level are unclear. We investigated this for
      dengue surveillance data provided online by the WHO. METHODS AND FINDINGS: We
      extracted all dengue surveillance data provided online by WHO Headquarters and
      Regional Offices (RO's). We assessed the availability and consistency of these
      data by comparing indicators within and between sources. We also assessed the
      consistency of dengue data provided online by two example countries (Brazil and
      Indonesia). Data were available from WHO for 100 countries since 1955
      representing a total of 23 million dengue cases and 82 thousand deaths ever
      reported to WHO. The availability of data on DengueNet and some RO's declined
      dramatically after 2005. Consistency was lacking between sources (84% across all
      indicators representing a discrepancy of almost half a million cases). Within
      sources, data at high spatial resolution were often incomplete. CONCLUSIONS: The
      decline of publicly available, integrated dengue surveillance data at the global
      level will limit opportunities for research, policy, and advocacy. A new
      financial and operational framework will be necessary for innovation and for the
      continued availability of integrated country disease data at the global level.

PMID- 25874805
TI  - Health and economic outcomes of introducing the new MenB vaccine (Bexsero) into
      the Italian routine infant immunisation programme.
AB  - INTRODUCTION: In January 2013 a novel type of multicomponent protein-based
      vaccine against group B meningococcal disease was licensed by the European
      Medicines Agency. With the widespread use of the meningococcal serogroup C
      conjugate vaccines, serogroup B remains now the major cause of bacterial
      meningitis and septicaemia in young children in Europe. The aim of this study is
      to investigate the health and the economic outcomes of MenB vaccine introduction
      into the Italian routine mass vaccination programme. METHODS: The present work is
      structured in two main parts. Firstly, we assess the epidemiological burden of
      group B meningococcal disease using official hospitalisation and notification
      data from two of the most populated Italian regions (Lombardia and Piemonte)
      during a 6-year study period (2007-2012). Secondly, we evaluate the cost
      effectiveness of the immunisation programme in Italy from the public health payer
      perspective under base case parameters assumptions and performing a comprehensive
      sensitivity analysis to assess the robustness and the uncertainty of our model
      results. RESULTS: MenB serotype is responsible for 59% of the 341 cases of
      Invasive Meningococcal Disease in Lombardia and Piemonte. Incidence rate for MenB
      infection is estimated to be 0.21/100,000/y resulting at the highest level in
      children <=4 years of age. Although the new MenB vaccine can potentially prevent
      about one third of the disease cases in the Italian population, model results
      show this strategy is unlikely to be cost-effective (ICER value over
      ?350,000/QALY) with a vaccine that prevents disease only. These results are
      robust under most of the sensitivity scenarios except when allowing for lower
      discount rates. DISCUSSION: The introduction of the novel vaccine into the
      routine immunisation schedule needs to be carefully evaluated. The new MenB
      vaccine has the potential to reduce the disease burden at the population level.
      However, from the Italian Health Service perspective, the immunisation programme
      is unlikely to be cost-effective at the current incidence levels and vaccine
      price.

PMID- 25874806
TI  - Aging with HIV vs. HIV seroconversion at older age: a diverse population with
      distinct comorbidity profiles.
AB  - OBJECTIVE: People aging with HIV might have different health conditions compared
      with people who seroconverted at older ages. The study objective was to assess
      the prevalence of, and risk factors for, individual co-morbidities and
      multimorbidity (MM) between HIV-positive patients with a longer duration of HIV
      infection, and patients who seroconverted at an older age. We compared estimates
      across both groups to a matched community-based cohort sampled from the general
      population. METHODS: We performed a case-control study including antiretroviral
      therapy (ART)-experienced patients who were HIV seropositive for >= 20.6 years
      ("HIV-Aging"), or who were seropositive for < 11.3 years ("HIV-Aged") having
      access in 2013 at the Modena HIV Metabolic Clinic. Patients were matched in a 1:3
      ratio with controls from the CINECA ARNO database. MM was defined as the
      concurrent presence of >2 NICM. Logistic regression models were constructed to
      evaluate associated predictors of NICM and MM. RESULTS: We analysed 404 HIV-Aging
      and 404 HIV-Aged participants in comparison to 2424 controls. The mean age was
      46.7 +/- 6.2 years, 28.9% were women. Prevalence of HIV co-morbidities and MM
      were significantly higher in the HIV-positive groups compared to the general
      population (p<0.001) and a trend towards higher rates of MM was found in aging vs
      aged group. This difference turned to be significant in patients above the age of
      45 years old (p<0.001). CONCLUSIONS: People aging with HIV display heterogeneous
      health conditions. Host factors and duration of HIV infection are associated with
      increased risk of MM compared to the general population.

PMID- 25874807
TI  - Maternal uptake of pertussis cocooning strategy and other pregnancy related
      recommended immunizations.
AB  - Maternal immunization is an important strategy to prevent severe morbidity and
      mortality in mothers and their offspring. This study aimed to identify whether
      new parents were following immunization recommendations prior to pregnancy,
      during pregnancy, and postnatally. A cross-sectional survey was conducted by a
      questionnaire administered antenatally to pregnant women attending a maternity
      hospital with a follow-up telephone interview at 8-10 weeks post-delivery.
      Factors associated with uptake of pertussis vaccination within the previous 5 y
      or postnatally and influenza vaccination during pregnancy were explored using log
      binomial regression models. A total of 297 pregnant women completed the
      questionnaire. For influenza vaccine, 20.3% were immunized during pregnancy and
      3.0% postnatally. For pertussis vaccine, 13.1% were vaccinated within 5 y prior
      to pregnancy and 31 women received the vaccine postnatally, 16 (51.6%) received
      the vaccine >4 weeks after delivery. Receiving a recommendation from a healthcare
      provider (HCP) was an independent predictor for receipt of both pertussis (RR
      2.07, p < 0.001) and influenza vaccine (RR 2.26, p = 0.001). Non-English speaking
      mothers were significantly less likely to have received pertussis vaccination
      prior to pregnancy or postnatally (RR 0.24, p = 0.011). Multiparous pregnant
      women were less likely to have received an influenza vaccine during their current
      pregnancy (p = 0.015). Uptake of pregnancy related immunization is low and likely
      due to poor knowledge of availability, language barriers and lack of
      recommendations from HCPs. Strategies to improve maternal vaccine uptake should
      include education about recommended vaccines for both HCPs and parents and
      written information in a variety of languages. 

PMID- 25874808
TI  - The effect of hormone therapy on all-cause and cardiovascular mortality in women
      with chronic kidney disease: protocol for a systematic review and meta-analysis.
AB  - BACKGROUND: Chronic kidney disease affects approximately one in ten North
      Americans and is associated with a high risk of cardiovascular disease. Chronic
      kidney disease in women is characterized by an abnormal sex hormone profile and
      low estradiol levels. Since low estradiol levels are associated with an increased
      cardiovascular risk in healthy women, our objective is to determine the effect of
      hormone therapy on all-cause mortality, cardiovascular mortality, and
      cardiovascular morbidity in women with chronic kidney disease. METHODS/DESIGN:
      Studies examining hormone therapy for adult women with chronic kidney disease
      will be included. The primary outcome is all-cause or cardiovascular mortality
      and morbidity. We will search electronic bibliographic databases (MEDLINE,
      EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL)) along
      with relevant conference proceedings, table of contents of journals, and review
      articles. Two investigators will independently screen identified abstracts and
      select observational cohort studies, case-control studies, and randomized
      controlled trials examining hormone therapy in women with chronic kidney disease.
      These investigators will also independently abstract data from relevant full-text
      journal articles and assess risk of bias. Where possible, these data will be
      summarized using pooled or combined estimates for the risk ratio or hazard ratio
      of all-cause mortality, cardiovascular mortality, and cardiovascular morbidity in
      women with chronic kidney disease with and without hormone therapy. A random
      effects model will be used, and meta-regression and subgroup analyses will be
      used to explore potential source of heterogeneity. DISCUSSION: Given the high
      burden of cardiovascular disease in women with chronic kidney disease, this study
      will help guide clinical practice by summarizing current evidence on the use of
      hormone therapy for prevention of all-cause mortality, cardiovascular mortality,
      and cardiovascular morbidity in this population. SYSTEMATIC REVIEW REGISTRATION:
      The final protocol was registered with PROSPERO ( CRD42014014566) .

PMID- 25874810
TI  - Dynamical study, hydrogen bond analysis, and constant pH simulations of the beta
      carbonic anhydrase of Methanobacterium thermoautotrophicum.
AB  - Within the five classes (alpha, beta, gamma, delta, and zeta) of carbonic
      anhydrases (CAs) the first two, containing mammal and plant representatives, are
      the most studied among all CAs. In this study, we have focused our investigation
      on the beta-class carbonic anhydrase of Methanobacterium thermoautotrophicum. We
      investigated both the importance of the Asp-Arg dyad near the catalytic zinc
      bound water and the possible roles that water molecules within the active site
      and residues near the entrance of the catalytic cleft have on the first step of
      the enzyme's reaction mechanism. Hydrogen-bonding analysis of selected residues
      within the active site and constant pH replica exchange molecular dynamics
      constant pH replica exchange simulations were performed. The latter was done in
      order to evaluate the pKa values of possible proton acceptors. We found an
      intricate hydrogen-bonding network involving two acidic residues within the
      active site, Asp16 and Asp34, and the catalytic water molecule. We also observed
      a very strong interaction between the zinc-bound water and residues Asp34 and
      Arg36. This interaction was not significantly affected by the change in the
      protonation state of both the catalytic water and aspartate residue 34. The pKa
      analysis show that the effect of the R36A mutation affects not only the possible
      proton acceptors, but also the catalytic water itself. 

PMID- 25874809
TI  - Mechanism of Inactivation of Neuronal Nitric Oxide Synthase by (S)-2-Amino-5-(2
      (methylthio)acetimidamido)pentanoic Acid.
AB  - Nitric oxide synthase (NOS) catalyzes the conversion of l-arginine to l
      citrulline and the second messenger nitric oxide. Three mechanistic pathways are
      proposed for the inactivation of neuronal NOS (nNOS) by (S)-2-amino-5-(2
      (methylthio)acetimidamido)pentanoic acid (1): sulfide oxidation, oxidative
      dethiolation, and oxidative demethylation. Four possible intermediates were
      synthesized. All compounds were assayed with nNOS, their IC50, KI, and kinact
      values were obtained, and their crystal structures were determined. The
      identification and characterization of the products formed during inactivation
      provide evidence for the details of the inactivation mechanism. On the basis of
      these studies, the most probable mechanism for the inactivation of nNOS involves
      oxidative demethylation with the resulting thiol coordinating to the cofactor
      heme iron. Although nNOS is a heme-containing enzyme, this is the first example
      of a NOS that catalyzes an S-demethylation reaction; the novel mechanism of
      inactivation described here could be applied to the design of inactivators of
      other heme-dependent enzymes. 

PMID- 25874811
TI  - A novel frameshift MSX1 mutation in a Saudi family with autosomal dominant
      premolar and third molar agenesis.
AB  - OBJECTIVES: In this study, the aim was to investigate a consanguineous Saudi
      family with non-syndromic premolars and third molars agenesis and to identify the
      causal mutation(s) using whole exome sequencing. DESIGN: Family phenotype and
      family pedigree were constructed from clinical and radiographic examinations.
      Whole exome sequencing was performed in two affected members of the Saudi family
      using the SureSelect Human all Exon 50 Mb kit (Agilent Technologies, Inc., Santa
      Clara, CA) and then sequenced on an Illumina HiSeq. SNP and indel calling were
      performed using samtools version 0.18 and were annotated using the software
      ANNOVAR. RESULTS: The family pedigree showed that the inheritance was autosomal
      dominant. Whole exome sequencing revealed that the affected members in this
      family were heterozygous with a novel frameshift mutation in exon 2 of the MSX1
      gene, (NM_002448:c.750_751insACCGGCTGCC, p.F251PfsX92). CONCLUSIONS: The novel
      MSX1 frameshift mutation was linked to a family with moderate to severe tooth
      agenesis phenotype affecting second premolars and third molars in both arches.
      This expands the genotype-phenotype of MSX1 associated conditions.

PMID- 25874812
TI  - Anxiolytic efficacy of repeated oral capsaicin in rats with partial aberration of
      oral sensory relay to brain.
AB  - OBJECTIVE: This study was conducted to examine if taste over load with oral
      capsaicin improves the adverse behavioural effects induced by partial aberration
      of oral sensory relays to brain with bilateral transections of the lingual and
      chorda tympani nerves. DESIGN: Male Sprague-Dawley rats received daily 1 ml of
      0.02% capsaicin or water drop by drop into the oral cavity following the
      bilateral transections of the lingual and chorda tympani nerves. Rats were
      subjected to ambulatory activity, elevated plus maze and forced swim tests after
      11th, 14th and 17th daily administration of capsaicin or water, respectively. The
      basal and stress-induced plasma corticosterone levels were examined after the end
      of behavioural tests. RESULTS: Ambulatory counts, distance travelled, centre zone
      activities and rearing were increased, and rostral grooming decreased, during the
      activity test in capsaicin treated rats. Behavioural scores of capsaicin rats
      during elevated plus maze test did not differ from control rats. Immobility
      during the swim test was decreased in capsaicin rats with near significance (P =
      0.0547). Repeated oral capsaicin increased both the basal level and stress
      induced elevation of plasma corticosterone in rats with bilateral transections of
      the lingual and chorda tympani nerves. DISCUSSION: It is concluded that repeated
      oral administration of capsaicin reduces anxiety-like behaviours in rats that
      received bilateral transections of the lingual and chorda tympani nerves, and
      that the increased corticosterone response, possibly modulating the hippocampal
      neural plasticity, may be implicated in the anxiolytic efficacy of oral
      capsaicin.

PMID- 25874813
TI  - The effects of xylitol and sorbitol on lysozyme- and peroxidase-related enzymatic
      and candidacidal activities.
AB  - OBJECTIVE: To investigate whether xylitol and sorbitol affect enzymatic and
      candidacidal activities of lysozyme, the peroxidase system, and the glucose
      oxidase-mediated peroxidase system. DESIGN: Xylitol and sorbitol were added to
      hen egg-white lysozyme, bovine lactoperoxidase, glucose oxidase-mediated
      peroxidase, and whole saliva in solution and on hydroxyapatite surfaces. The
      enzymatic activities of lysozyme, peroxidase, and glucose oxidase-mediated
      peroxidase were determined by the turbidimetric method, the NbsSCN assay, and
      production of oxidized o-dianisidine, respectively. Candidacidal activities were
      determined by comparing colony forming units using Candida albicans ATCC strains
      10231, 11006, and 18804. RESULTS: While xylitol and sorbitol did not affect the
      enzymatic activity of hen egg-white lysozyme both in solution and on
      hydroxyapatite surfaces, they did inhibit the enzymatic activity of salivary
      lysozyme significantly in solution, but not on the surfaces. Xylitol and sorbitol
      enhanced the enzymatic activities of both bovine lactoperoxidase and salivary
      peroxidase significantly in a dose-dependent manner in solution, but not on the
      surfaces. Sorbitol, but not xylitol, inhibited the enzymatic activity of glucose
      oxidase-mediated peroxidase significantly. Both xylitol and sorbitol did not
      affect candidacidal activities of hen egg-white lysozyme, the bovine
      lactoperoxidase system, or the glucose oxidase-mediated bovine lactoperoxidase
      system. CONCLUSIONS: Xylitol and sorbitol inhibited salivary lysozyme activity,
      but enhanced both bovine lactoperoxidase and salivary peroxidase activities
      significantly in solution. Xylitol and sorbitol did not augment lysozyme- and
      peroxidase-related candidacidal activities.

PMID- 25874814
TI  - Effect of epithelial cells derived from periodontal ligament on osteoblast-like
      cells in a Transwell membrane coculture system.
AB  - BACKGROUND AND OBJECTIVE: The epithelial rests of Malassez (ERM) are
      developmental residues of Hertwig's epithelial root sheath, and they are present
      throughout life in the periodontal ligament. Previous studies have shown that ERM
      induce cementogenesis or inhibit cement-osteogenesis. This study investigated how
      ERM cells are involved in osteoblast mineralization in an in vitro coculture
      system. MATERIALS AND METHODS: ERM cells were isolated from porcine periodontal
      ligament by an outgrowth method. Osteoblast-like MC3T3-E1 cells were cocultured
      with ERM or gingival epithelium (GE) cells in six-well Transwell units.
      Mineralization of MC3T3-E1 cells was confirmed by Alizarin Red staining after 30
      days of culture. Alkaline phosphatase (ALP) activity was measured in the culture
      media. To examine whether enamel matrix proteins are involved in the
      mineralization of MC3T3-E1 cells, an anti-amelogenin antibody was added to the
      culture media. RESULTS: The staining by Alizarin Red of MC3T3-E1 cells cocultured
      with ERM cells was clearly weaker than that in the GE cell coculture. The ALP
      activity in the ERM cell coculture was significantly lower than that in the GE
      cell coculture (p < 0.05). Alizarin Red staining of MC3T3-E1 cells in the ERM
      cell coculture with anti-amelogenin antibody was clearly stronger than in those
      cocultures without the antibody at 30 days. The ALP activity in the ERM cell
      coculture with anti-amelogenin antibody was significantly higher than in those
      cultures without the antibody (p < 0.05). CONCLUSION: This study demonstrated
      that ERM cells inhibit the calcification of osteoblast-like cells in a Transwell
      coculture system and that this inhibition is reversed with an anti-amelogenin
      antibody.

PMID- 25874815
TI  - Microscopic study of dental hard tissues in primary teeth with Dentinogenesis
      Imperfecta Type II: Correlation of 3D imaging using X-ray microtomography and
      polarising microscopy.
AB  - OBJECTIVES: The aim of this study was to examine the histological appearance of
      dental hard tissues in primary teeth from children with DI using conventional
      polarised light microscopy and correlate that with 3D imaging using X-ray
      microtomograpy (XMT) to gain a further understanding of the dentine structure of
      teeth diagnosed with dentinogenesis imperfecta. DESIGN: Undecalcified sections of
      primary teeth from patients diagnosed with Dentinogenesis Imperfecta Type II were
      examined using polarised light microscopy. XMT was employed for 3D-imaging and
      analysis of the dentine. RESULTS: The polarised light microscopy and XMT revealed
      tubular structures in the dentine seen as vacuoles coinciding with the path of
      normal dentinal tubules but not continuous tubules. The size of the tubules was
      close to that of capillaries. The largest tubular structures had a direction
      corresponding to where the pulp tissue would have been located during primary
      dentine formation. The dysfunctional mineralisation of the dentine and
      obliteration of the pulp evidently leaves blood vessels in the dentine which have
      in the main been tied off and, in the undecalcified sections, appear as vacuoles.
      CONCLUSIONS: Although from radiographs, the pulp in teeth affected by
      Dentinogenesis Imperfect type II appears to be completely obliterated, a network
      of interconnected vessels may remain. The presence of large dentinal tubules and
      blood vessels, or the remnants of blood vessels, could provide a pathway for
      bacteria from the oral cavity. This might account for why some of these teeth
      develop periapical abscesses in spite of apparently having no pulp.

PMID- 25874816
TI  - Induction of antiviral responses against avian influenza virus in embryonated
      chicken eggs with toll-like receptor ligands.
AB  - Early responses against viruses, such as avian influenza virus (AIV), may be
      induced by Toll-like receptor (TLR) pathways. In the present study, an in ovo
      model was employed to study the antiviral activities of TLR ligands. It was
      hypothesized that administration of TLR ligands in ovo at the appropriate dose
      and time can reduce AIV titer in embryonated chicken eggs. Moreover, the study
      aimed to determine the mechanisms involved in the TLR-mediated antiviral
      responses in the chorioallantoic membrane (CAM). Embryonated eggs (10-14 day old)
      were treated with TLR2, 4, 7, and 21 ligands using different doses and times pre-
      and post-AIV infection. The results revealed that treatment of embryonated
      chicken eggs with TLR ligands reduced AIV replication. Further analysis showed
      that TLR ligands induced interferon (IFN)-gamma and IFN stimulatory genes in the
      CAM, which may have played a role in the reduction of the AIV titer. The timing
      and dose of TLR ligands administration had significant impacts on the outcome of
      the treated eggs. In conclusion, the present study demonstrated that the in ovo
      route may be employed to determine the antiviral characteristics of TLR ligands
      against AIV. 

PMID- 25874817
TI  - Facilities, breed and experience affect ease of sheep handling: the livestock
      transporter's perspective.
AB  - An understanding of the perceived importance of a variety of factors affecting
      the ease of handling of sheep and the interactions between these factors is
      valuable in improving profitability and welfare of the livestock. Many factors
      may contribute to animal behaviour during handling, and traditionally these
      factors have been assessed in isolation under experimental conditions. A human
      social component to this phenomenon also exists. The aim of this study was to
      gain a deeper understanding of the importance of a variety of factors affecting
      ease of handling, and the interactions between these from the perspective of the
      livestock transporter. Qualitative interviews were used to investigate the
      factors affecting sheep behaviour during handling. Interview transcripts
      underwent thematic analysis. Livestock transporters discussed the effects of
      attitudes and behaviours towards sheep, helpers, facilities, distractions,
      environment, dogs and a variety of sheep factors including breed, preparation,
      experience and sex on sheep behaviour during handling. Transporters demonstrated
      care and empathy and stated that patience and experience were key factors
      determining how a person might deal with difficult sheep. Livestock transporters
      strongly believed facilities (ramps and yards) had the greatest impact, followed
      by sheep experience (naivety of the sheep to handling and transport) and breed.
      Transporters also discussed the effects of distractions, time of day, weather,
      dogs, other people, sheep preparation, body condition and sheep sex on ease of
      handling. The concept of individual sheep temperament was indirectly expressed. 

PMID- 25874818
TI  - Fuji apple storage time rapid determination method using Vis/NIR spectroscopy.
AB  - Fuji apple storage time rapid determination method using visible/near-infrared
      (Vis/NIR) spectroscopy was studied in this paper. Vis/NIR diffuse reflection
      spectroscopy responses to samples were measured for 6 days. Spectroscopy data
      were processed by stochastic resonance (SR). Principal component analysis (PCA)
      was utilized to analyze original spectroscopy data and SNR eigen value. Results
      demonstrated that PCA could not totally discriminate Fuji apples using original
      spectroscopy data. Signal-to-noise ratio (SNR) spectrum clearly classified all
      apple samples. PCA using SNR spectrum successfully discriminated apple samples.
      Therefore, Vis/NIR spectroscopy was effective for Fuji apple storage time rapid
      discrimination. The proposed method is also promising in condition safety control
      and management for food and environmental laboratories. 

PMID- 25874819
TI  - Dissemination of Enterococcus faecalis and Enterococcus faecium in a ricotta
      processing plant and evaluation of pathogenic and antibiotic resistance profiles.
AB  - In this work, the sources of contamination by Enterococcus spp. in a ricotta
      processing line were evaluated. The isolated strains were tested for virulence
      genes (gelE, cylA,B, M, esp, agg, ace, efaA, vanB), expression of virulence
      factors (hemolysin and gelatinase), and the resistance to 10 different
      antibiotics. Enterococcus faecium and Enterococcus faecalis were subjected to
      discriminatory identification by intergenic spacer region (ITS)-polymerase chain
      reaction and sequencing of the ITS region. The results showed that Enterococcus
      spp. was detected in the raw materials, environment samples and the final
      product. None of the 107 Enterococcus isolates were completely free from all
      virulence genes considered. A fraction of 21.5% of the isolates containing all of
      the genes of the cylA, B, M operon also expressed beta-hemolysis. Most of the
      isolates showed the gelE gene, but only 9.3% were able to hydrolyze gelatin. In
      addition, 23.5% of the observed Enterococcus isolates had the vanB gene but were
      susceptible to vancomycin in vitro. The dissemination of antibiotic-resistant
      enterococci was revealed in this study: 19.3% of the E. faecium samples and 78.0%
      of the E. faecalis samples were resistant to at least one of the antibiotics
      tested. Sequencing of region discriminated 5 and 7 distinct groups among E.
      faecalis and E. faecium, respectively. Although some similarity was observed
      among some of the isolates, all E. faecalis and E. faecium isolates had genetic
      differences both in the ITS region and in the virulence profile, which makes them
      different from each other. 

PMID- 25874820
TI  - Potential Synergy of Radiation Therapy With Vismodegib for Basal Cell Carcinoma.

PMID- 25874821
TI  - Preventing 'where next?' Patients, professionals and learning from serious
      failings in care.

PMID- 25874822
TI  - Quality and safety in acute medical care - what can design bring to the table?

PMID- 25874823
TI  - Alcohol and the developing adolescent brain: evidence review.

PMID- 25874824
TI  - Thinking about Ebola.

PMID- 25874825
TI  - Ebola: a West African perspective.

PMID- 25874826
TI  - Most Scottish neurologists do not apply the 2010 McDonald criteria when
      diagnosing multiple sclerosis.
AB  - BACKGROUND: The diagnostic criteria for multiple sclerosis have evolved over time
      and currently the 2010 McDonald criteria are the most widely accepted. These
      criteria allow the diagnosis of multiple sclerosis to be made at the clinically
      isolated syndrome stage provided certain criteria are met on a single magnetic
      resonance brain scan. Our hypothesis was that neurologists in Scotland did not
      use these criteria routinely. METHOD: We sent a SurveyMonkey questionnaire to all
      Scottish neurologists (consultants and trainees) regarding the diagnosis of
      multiple sclerosis. RESULTS: Our questionnaire response rate was 65/99 (66%).
      Most Scottish neurologists were aware of the criteria and 31/58 (53%) felt that
      they were using these routinely. However, in a clinical vignette designed to test
      the application of these criteria, only 5/57 (9%) of neurologists appeared to use
      them. CONCLUSION: Scottish neurologists' use of the 2010 McDonald criteria for
      diagnosis of multiple sclerosis varies from practitioners' perception of their
      use of these criteria.

PMID- 25874827
TI  - Potential costs of B-type natriuretic peptide for the identification of people
      with heart failure in primary care in Scotland - a pilot study.
AB  - BACKGROUND AND AIMS: The utility of B-type natriuretic peptide as a screening
      test for heart failure has been proven in a number of clinical trials. The aims
      of this study were to assess the utility of the measurement of B-type natriuretic
      peptide in a 'real life' setting and to estimate the potential costs of
      implementing its use in primary care in Scotland. METHODS AND RESULTS: Eight
      general practitioner practices with a combined population of approximately 62,000
      were invited to participate. During the 9-month study period, 82 samples for B
      type natriuretic peptide measurement were requested. The negative predictive
      value for B-type natriuretic peptide was 96.9%. Compared with
      electrocardiography, B-type natriuretic peptide reduced the need for
      echocardiography by 308 tests per million population per year. The estimated cost
      of implementation in Scotland is approximately L220,000 per annum, equating to
      L64.93 per patient correctly diagnosed with heart failure, with a potential
      saving in echocardiography of L110,800. CONCLUSION: In this pilot study,
      measurement of plasma B-type natriuretic peptide in a 'real life' setting in
      primary care had a similar sensitivity, specificity and negative predictive value
      to that observed in trial populations. B-type natriuretic peptide aids early
      diagnosis of heart failure in primary care and may help to facilitate prompt
      introduction of evidence based therapies to modify patient outcomes. The costs of
      measuring plasma B-type natriuretic peptide in suspected cases of heart failure
      are modest, and its use would increase the diagnostic capacity of primary care if
      supported by local cardiology services.

PMID- 25874828
TI  - Diabetes in the young - a case of Alstrom syndrome with myopathy.
AB  - Alstrom syndrome is a rare ciliopathy affecting about 1 in 1,000,000 individuals.
      It is characterised by cone-rod dystrophy, insulin resistance, diabetes mellitus,
      cardiomyopathy, renal failure and hypogonadism. Progressive multi-organ
      dysfunction eventually leads to death. Only about 800 patients with this disorder
      have been identified so far. The diagnosis of Alstrom syndrome is critical as it
      can easily be overlooked because of the many features it shares with metabolic
      syndrome. The gene affected in this autosomal recessive disease is ALMS1, the
      protein product of which is involved in intracellular trafficking and ciliary
      function. Alstrom syndrome is being studied as a model which would potentially
      shed light on the pathophysiology of diabetes mellitus. In this report, we
      describe a patient with features of Alstrom syndrome and a clinical picture
      suggestive of a recurrent, severe, steroid responsive myopathy which, to the best
      of our knowledge, has not been reported so far.

PMID- 25874830
TI  - Intra-arterial treatment in acute ischaemic stroke: what we learn from the MR
      CLEAN trial.

PMID- 25874829
TI  - Leprosy: a 'common' and curable cause of peripheral neuropathy with skin lesions.
AB  - Leprosy (or Hansen's disease) is a curable chronic infectious disease caused by
      the acid-fast bacillus Mycobacterium leprae. While leprosy remains one of the
      most common causes of neuropathy worldwide, its rarity in the UK means that many
      doctors are unfamiliar with the typical clinical features. This is problematic
      because early recognition and treatment is vital in order to minimise disease
      related complications such as nerve injury. We describe a 75-year-old man who
      presented with multiple mononeuropathy (mononeuritis multiplex, particularly
      affecting the ulnar nerves) and typical granulomatous skin lesions, in whom the
      diagnosis was made on the basis of skin biopsy. We highlight the clinical
      features, investigations and treatment of the patient, and provide information
      about the epidemiology and pathogenesis of leprosy. 

PMID- 25874831
TI  - Parenteral nutrition.
AB  - Over the last 50 years, parenteral nutrition has been recognised as an invaluable
      and potentially lifesaving tool in the physician's arsenal in the management of
      patients with intestinal failure or inaccessibility; however, it may also be
      associated with a number of potentially life-threatening complications. A recent
      NCEPOD report (2010) identified a number of inadequacies in the overall provision
      and management of parenteral nutrition and recommendations were made with the aim
      of improving clinical practice in the future. This paper focuses on the practical
      aspects relating to parenteral nutrition for adults, including important
      concepts, such as patient selection, as well as general management. We also
      explore the various pitfalls and potential complications and how these may be
      minimised. 

PMID- 25874832
TI  - Enteral tube feeding in adults.
AB  - Enteral tube feeding is usually a relatively straightforward method of
      nutritional support, and should be facilitated by a multiprofessional team. For
      short-term use (<4 weeks) a fine bore feeding nasogastric tube is indicated but
      if longer term feeding is required then a gastrostomy is appropriate, usually
      inserted endoscopically (a percutaneous endoscopic gastrostomy tube). The most
      common serious complication of a nasogastric tube is not identifying a misplaced
      tube within the lungs: there are clear recommendations from the National Patient
      Safety Agency as to how to check tube placement. Nasojejunal tubes are required
      in patients with gastroparesis. Tube blockage is common and is prevented by
      careful and regular flushing. Diarrhoea is the most complication of feeding and
      is often related to other medication. Clinicians need an algorithm for
      systematically dealing with such a problem. Refeeding syndrome may occur in
      malnourished patients and is characterised by low levels of potassium, phosphate,
      and/or magnesium, as well as disorders of water and salt balance. Identifying the
      at-risk patient with careful monitoring is crucial. 

PMID- 25874833
TI  - Psychological aspects of endocrine disease.
AB  - This review illustrates how an innovative psychoneuroendocrine approach to
      endocrine patients may improve their management. Important psychological issues
      pertain to all the different phases of an endocrine disorder. Before disease
      onset, stressful life events may play a pathogenetic role and, together with
      chronic stress, may contribute to a cumulative burden also called allostatic
      load; psychological and psychiatric symptoms are common both in the prodromal and
      in the active phase of illness; after cure or remission, there could be residual
      symptoms and impaired quality of life that deserve attention. All these aspects
      should be taken into consideration and introduced in current endocrine care and
      practice. 

PMID- 25874834
TI  - The rise and fall of uroscopy as a parable for the modern physician.
AB  - As the first documented laboratory test in history, urinalysis, (or 'uroscopy' as
      it was historically referred to), was revered as the ultimate skill for
      physicians. The matula, in which the physician would pensively inspect his urine,
      would become an emblem of physician status and omniscience, a glass bladder that
      held the power to foretell a patient's future. It would also reveal much about
      how early physicians refined the scientific method, evolving their practice from
      that of speculation and magic and adopting more rigour in their analysis.
      However, the practice of uroscopy fell from grace as rogue physicians and
      charlatans began exploiting its reputation for dishonest gain and deception of
      patients. For this reason, the practice of uroscopy is intriguing - its rise and
      fall reflect the haphazard chase for a 'silver bullet' diagnostic tool which we
      would do well to remember today. 

PMID- 25874835
TI  - The Monros - three medical dynasties with a common origin.
AB  - From origins in their heartlands in Easter Ross, clan Munro produced no fewer
      than three distinct medical dynasties, all descended from Hugh Munro, 9th Baron
      Foulis (c1352-1425), 12th chief of the clan. This paper describes what we believe
      to be a unique family of related medical dynasties which were influential in
      Edinburgh, London and the Scottish Highlands. It sets out in detail the family
      genealogy, provides some biographical information, and explores the reasons for
      the development of such medical dynasties, which appear to be different for each
      of the three dynasties within this family. The 'Edinburgh Monros' included the
      three Alexanders Monro, primus, secundus and tertius, who between them occupied
      the university chair of Anatomy at the University of Edinburgh for 126 years from
      1720. Dr David Monro, son of Alexander Monro tertius, emigrated to New Zealand
      where his descendants included several doctors, the last of whom died in 2013.
      The 'Bedlam Monros' achieved fame, and some notoriety, in managing mental illness
      in London for the 154 years from 1728-1882. In contrast, the 'Bonesetter Munros'
      practised their skills in the local community in Ross-shire and one of them
      attracted patients from all over Britain. They practised their trade for over 100
      years from the start of the 19th to the early 20th century. 

PMID- 25874836
TI  - Maternity records in Edinburgh and Aberdeen in 1936: a comparison.
AB  - Historians have long used maternity records to understand the evolution of
      maternity services. More recently, epidemiologists have become interested in
      obstetric hospital records as a source of data (e.g. birth weight, social class),
      to study the influence of early life on future health and disease: life course
      epidemiology. Edinburgh and Aberdeen are unusual in holding detailed records from
      several maternity institutions. The records of 1936 are of particular interest
      because all children born in this year and at school in Scotland at age 11 sat a
      cognitive ability test, the Scottish Mental Survey 1947. This study aims to
      describe the maternity services in Edinburgh and Aberdeen in 1936, between the
      First and Second World Wars. Understanding the richness of data in birth records,
      the manner in which they were recorded, and the context of the institutions in
      their community is essential for interpreting life course epidemiology studies. 

PMID- 25874837
TI  - James Parkinson's essay on the shaking palsy.

PMID- 25874838
TI  - Improvements in palliative and end of life care require a new approach to change.

PMID- 25874839
TI  - The safety and efficacy of vortioxetine for acute treatment of major depressive
      disorder: a systematic review and meta-analysis.
AB  - BACKGROUND: Vortioxetine is the first mixed serotonin agonist and antagonist
      antidepressant approved in the US. We sought to evaluate all published and
      unpublished data available to determine the efficacy and harms of vortioxetine in
      adults with major depressive disorder. METHODS: We used a predefined search
      strategy of MEDLINE, the Cochrane Central Register of Controlled Trials,
      ClinicalTrials.gov, and Drugs@FDA to identify studies evaluating vortioxetine in
      the acute treatment of major depressive disorder. Only randomized controlled
      trials (RCTs) that provided results on relevant clinical efficacy and safety
      outcomes were included. Study quality was assessed and results were pooled using
      mixed effect meta-analyses where applicable. RESULTS: We identified 11 RCTs with
      6,145 participants meeting inclusion criteria (eight were published and three
      were unpublished). The trials did not exceed 8 weeks in duration. The response
      rate with vortioxetine was significantly higher for 1-mg (relative risk (RR) =
      1.91; 95% confidence interval (CI) 1.36 to 2.69), 5-mg (RR = 1.33; 95% CI 1.10 to
      1.61), 10-mg (RR = 1.42; 95% CI 1.21 to 1.67), and 20-mg doses (RR = 1.58; 95% CI
      1.19 to 2.08) compared to placebo. Remission rates were significantly higher for
      the 10-mg group (RR = 1.45; 95% CI 1.18 to 1.77) and the 20-mg group (RR = 1.68;
      95% CI 1.19 to 2.37) compared to placebo. Meta-regression of dose on the log odds
      ratio of response was not statistically significant (beta = 0.01; P = 0.46).
      Vortioxetine response rates were lower than active serotonin and norepinephrine
      reuptake inhibitor (SNRI) comparators for the 5-mg (RR = 0.88; 95% CI 0.80 to
      0.98), 15-mg (RR = 0.78; 95% CI 0.68 to 0.90), and 20-mg (RR = 0.82; 95% CI 0.72
      to 0.94) doses. The most common adverse events were nausea and vomiting which
      increased in frequency with higher doses. CONCLUSIONS: Vortioxetine was
      significantly more effective than placebo for acute treatment of major depressive
      disorder (MDD). Although treatment effect estimates varied substantially between
      studies, a dose effect was not observed. Vortioxetine does not appear to be more
      effective, and is potentially less effective, than an SNRI. SYSTEMATIC REVIEW
      REGISTRATION: PROSPERO CRD42013006198 .

PMID- 25874840
TI  - Tandem mass spectrometry analysis of linoleic and arachidonic acid hydroperoxides
      via promotion of alkali metal adduct formation.
AB  - Recently, we demonstrated that tandem mass spectrometry (MS/MS) analysis in the
      presence of sodium ions was useful for identification of the position of the
      hydroperoxy group in phosphatidylcholine hydroperoxide (PCOOH). Likewise, MS/MS
      may enable identification of the hydroperoxy group position in various lipid
      hydroperoxides (LOOHs). To this end, we prepared major LOOHs, namely
      hydroperoxyoctadecadienoic acid (HPODE) and hydroperoxyeicosatetraenoic acid
      (HPETE), and analyzed them by quadrupole-time-of-flight MS/MS in both the absence
      and presence of alkali metals. Photo-oxidation (singlet oxygen-induced oxidation)
      of linoleic acid (LA) was used to prepare 9-10E,12Z-HPODE, 9-10E,12E-HPODE, 10
      8E,12Z-HPODE, 12-9Z,13E-HPODE, 13-9Z,11E-HPODE, and 13-9E,11E-HPODE. Each isomer
      was analyzed under various MS/MS conditions (e.g., absence and presence of
      sodium). We found that in the presence of alkali metals, especially sodium,
      collision-induced dissociation (CID) of all HPODE isomers yielded structure
      diagnostic fragment ions that were highly useful in identifying the position of
      the hydroperoxy group. For instance, CID spectra of sodiated 13-9Z,11E-HPODE
      revealed a neutral loss of 88 Da arising from fragmentation of the hydroperoxy
      group. Similar results were observed for HPETE isomers. Following oxidation of LA
      (or arachidonic acid) by lipoxygenase, the hydroperoxy group position of the
      resultant HPODE (or HPETE) was easily identified using this method, without any
      chromatographic separation processes. As information on the position of the
      hydroperoxy group provides insight into the processes that initiate lipid
      peroxidation (e.g., enzymatic oxidation, auto-oxidation and singlet oxygen
      induced oxidation), the proposed method may be useful in elucidating the
      involvement and mechanism of lipid peroxidation in food deterioration and
      pathophysiological processes. 

PMID- 25874841
TI  - Bacterial genetics: Metalloregulatory riboswitches.

PMID- 25874842
TI  - Bugs full of viruses.

PMID- 25874844
TI  - The dependency of tunnel magnetoresistance ratio on nanoscale thicknesses of
      Co2Fe6B2 free and pinned layers for Co2Fe6B2/MgO-based perpendicular-magnetic
      tunnel-junctions.
AB  - The tunnel magnetoresistance (TMR) ratio of a cobalt-iron-boron (CoFeB)-based
      perpendicular-magnetic-tunnel-junction (p-MTJ) spin valve is extremely sensitive
      to both nanoscale Co2Fe6B2 free- and pinned-layer thicknesses. The TMR ratio
      peaks at a Co2Fe6B2 free-layer thickness of 1.05 nm, while it peaks at a Co2Fe6B2
      pinned-layer thickness of 1.59 nm, achieving 104%. The amount of tantalum
      diffused into the MgO tunneling barrier (originated from a tantalum seed)
      decreases with increasing Co2Fe6B2 free-layer thickness, while the amount of
      palladium diffused from a [Co/Pd]n SyAF layer decreases with increasing Co2Fe6B2
      pinned-layer thickness, determining the crystallinity of the MgO tunneling
      barrier and the TMR ratio. In addition, the TMR ratio tended to decrease when the
      Co2Fe6B2 free layer and the Co2Fe6B2 pinned layer switched characteristics from
      interface-perpendicular anisotropic to in-plane anisotropic. 

PMID- 25874843
TI  - Mechanisms of ribosome rescue in bacteria.
AB  - Ribosomes that stall during translation need to be rescued to ensure that the
      protein synthesis capacity of the cell is maintained. Stalling arises when
      ribosomes become trapped at the 3' end of an mRNA, which occurs when a codon is
      unavailable, as this leads to the arrest of elongation or termination. In
      addition, various factors can induce ribosome stalling in the middle of an mRNA,
      including the presence of specific amino acid sequence motifs in the nascent
      polypeptide. Almost all bacteria use a mechanism known as trans-translation to
      rescue stalled ribosomes, and some species also have other rescue mechanisms that
      are mediated either by the alternative ribosome-rescue factor A (ArfA) or ArfB.
      In this Review, I summarize the recent studies that have demonstrated the
      conditions that trigger ribosome stalling, the pathways that bacteria use to
      rescue stalled ribosomes and the physiological effects of these processes. 

PMID- 25874845
TI  - Craniovertebral tuberculosis in children: experience of 23 cases and proposal for
      a new classification.
AB  - PURPOSE: The aim of this study was to review cases of paediatric patients with
      craniovertebral junction (CVJ) tuberculosis with a view to try and stratify the
      cases into different groups which would help plan treatment and hence develop a
      protocol for treatment of a fairly uncommon condition still widely seen in the
      developing world. METHODS: Twenty-three cases of paediatric craniovertebral
      tuberculosis had their clinical features and radiology reviewed. The treatment
      plan in each case was analyzed according to their presentation. The results of
      treatment after 1 year were assessed in each case. RESULTS: The clinical
      presentations varied from neck pain with hypoglossal nerve palsy to frank spastic
      quadriparesis, and frank instability at the atlanto-axial junction was seen in
      five out of 23 patients. Cold abscesses were seen in 18/23 cases, and severe
      torticollis was the presentation in 6/23. We graded the children with this
      condition into three groups: 1) those with instability and gross neurodeficit who
      required early operative intervention (1 needed trans-oral decompression with
      posterior fixation and 4 required posterior fixation) 2) those who had severe
      torticollis and large cold abscesses who were treated with trans-oral aspiration
      of cold abscess followed by neck immobilization (6/23) and 3) those who did not
      have significant neck muscle spasm or torticollis and who were treated with
      immobilization alone (12/23). Only one child in group 3 required delayed
      intervention for instability which developed after completion of the course of
      anti-tubercular medication. CONCLUSIONS: We concluded that children with
      craniovertebral tuberculosis should be treated according to their clinical
      presentation coupled with evidence of radiological instability. Those with gross
      deficit and instability need early stabilization, those with minimal deficit and
      no instability but severe pain or torticollis need aspiration of the cold abscess
      with external immobilization, whereas those without deficit, instability or
      severe pain may be managed by external orthoses alone. Of course, medical
      treatment for tuberculosis is necessary in each case.

PMID- 25874846
TI  - Management of Chiari I malformation in children: effectiveness of intra-operative
      ultrasound for tailoring foramen magnum decompression.
AB  - PURPOSE: Patients with Chiari I malformation (CM-1) commonly undergo foramen
      magnum decompression (FMD). However, there is no consensus on how this should be
      achieved. An approach would be to rationalize surgical steps based on pre
      operative imaging and intra-operative findings. The aim of this study is to
      assess the usefulness of intra-operative ultrasound scanning (IOUS) in tailoring
      foramen magnum decompression in children with CM-1 and whether the use of IOUS is
      effective in reducing the risk of complications without increasing the need for
      re-operation. METHOD: We performed a retrospective study. IOUS was utilized
      during FMD: a subjective assessment was made on whether there was adequate
      cerebellar tonsillar and/or CSF pulsation following suboccipital craniectomy. If
      there was adequate pulsation, the dura was not opened. Additional data were
      collected including age and gender of patients, presence of pre-operative
      syringomyelia, intra-operative ultrasound findings, length of follow-up,
      complications and radiological and clinical outcome. The statistical analysis was
      performed with XLStat(r)(Addinsoft SARLTM, France). RESULTS: Nineteen patients
      underwent FMD from June 2011 to December 2012. The mean age was 10.5 years; there
      were nine females and ten males. Eleven patients had syringomyelia at diagnosis.
      Based on IOUS, eight patients underwent dural decompression and 11 patients bony
      decompression only. One patient had a post-operative pseudomeningocoele and two
      patients required re-operation. There was no significant statistical difference
      between the two groups regarding post-operative improvement in the syrinx.
      CONCLUSION: We found that tailoring FMD for patients with CM-1 using intra
      operative findings using ultrasound scan was useful in avoiding unnecessary
      manoeuvres, while not compromising on the outcome.

PMID- 25874847
TI  - Site-specific enzymatic introduction of a norbornene modified unnatural base into
      RNA and application in post-transcriptional labeling.
AB  - Inverse electron demand Diels-Alder cycloadditions have proven to be extremely
      useful for mild and additive-free orthogonal labeling of biomolecules, amongst
      others, for RNA labeling in vitro and in a cellular context. Here we present a
      method for site-specific introduction of an alkene modification into RNA via T7
      in vitro transcription. For this, an unnatural, hydrophobic base pairing system
      developed by Romesberg and coworkers was modified introducing one or two
      norbornene moieties at predefined positions into RNA oligonucleotides in an in
      vitro transcription reaction. This allows post-transcriptional functionalization
      of these RNA molecules with tetrazine derivatives containing for instance
      fluorophores or biotin. 

PMID- 25874848
TI  - An Examination of the Word Memory Test as a Measure of Memory.
AB  - This study examined the utility of the Word Memory Test (WMT) as a measure of
      verbal episodic memory by comparing select WMT subtests to the California Verbal
      Learning Test (CVLT) First and Second Editions (CVLT-II) across two samples.
      Correlations between the WMT and CVLT/CVLT-II subtests were statistically
      significant in the expected direction. Effect sizes were examined to assess the
      degree to which the WMT memory subtests and the CVLT First Edition subtests
      discriminated between groups of people who would be expected to differ from each
      other in verbal memory abilities. Comparison groups included cases of mild,
      moderate, and severe traumatic brain injury, mixed neurological patients, healthy
      adult controls, and patients with possible early dementia. Once invalid data were
      removed by studying only those who passed performance validity testing, it was
      found that the effect sizes between these groups were comparable. The WMT, CVLT,
      and CVLT-II were found to discriminate to about the same degree between people
      differing from each other in age, intelligence levels, and gender. Based on these
      data from a total sample of more than 3,000 cases, it is concluded that select
      WMT subtests are commensurate with the CVLT subtests as measures of memory within
      primarily disability-seeking samples. 

PMID- 25874851
TI  - Correction: a genome-wide perspective of miRNAome in response to high
      temperature, salinity and drought stresses in Brassica juncea (Czern) L.

PMID- 25874849
TI  - RNAi knockdown of oxytocin receptor in the nucleus accumbens inhibits social
      attachment and parental care in monogamous female prairie voles.
AB  - Oxytocin modulates many aspects of social cognition and behaviors, including
      maternal nurturing, social recognition and bonding. Natural variation in oxytocin
      receptor (OXTR) density in the nucleus accumbens (NAcc) is associated with
      variation in alloparental behavior, and artificially enhancing OXTR expression in
      the NAcc enhances alloparental behavior and pair bonding in socially monogamous
      prairie voles. Furthermore, infusion of an OXTR antagonist into the NAcc inhibits
      alloparental behavior and partner preference formation. However, antagonists can
      promiscuously interact with other neuropeptide receptors. To directly examine the
      role of OXTR signaling in social bonding, we used RNA interference to selectively
      knockdown, but not eliminate, OXTR in the NAcc of female prairie voles and
      examined the impact on social behaviors. Using an adeno-associated viral vector
      expressing a short hairpin RNA (shRNA) targeting Oxtr mRNA, we reduced accumbal
      OXTR density in female prairie voles from juvenile age through adulthood. Females
      receiving the shRNA vector displayed a significant reduction in alloparental
      behavior and disrupted partner preference formation. These are the first direct
      demonstrations that OXTR plays a critical role in alloparental behavior and adult
      social attachment, and suggest that natural variation in OXTR expression in this
      region alone can create variation in social behavior. 

PMID- 25874850
TI  - Chromosome VIII disomy influences the nonsense suppression efficiency and
      transition metal tolerance of the yeast Saccharomyces cerevisiae.
AB  - The SUP35 gene of the yeast Saccharomyces cerevisiae encodes the translation
      termination factor eRF3. Mutations in this gene lead to the suppression of
      nonsense mutations and a number of other pleiotropic phenotypes, one of which is
      impaired chromosome segregation during cell division. Similar effects result from
      replacing the S. cerevisiae SUP35 gene with its orthologues. A number of genetic
      and epigenetic changes that occur in the sup35 background result in partial
      compensation for this suppressor effect. In this study we showed that in S.
      cerevisiae strains in which the SUP35 orthologue from the yeast Pichia
      methanolica replaces the S. cerevisiae SUP35 gene, chromosome VIII disomy results
      in decreased efficiency of nonsense suppression. This antisuppressor effect is
      not associated with decreased stop codon read-through. We identified SBP1, a gene
      that localizes to chromosome VIII, as a dosage-dependent antisuppressor that
      strongly contributes to the overall antisuppressor effect of chromosome VIII
      disomy. Disomy of chromosome VIII also leads to a change in the yeast strains'
      tolerance of a number of transition metal salts.

PMID- 25874852
TI  - Interaction with Mixed Micelles in the Intestine Attenuates the Permeation
      Enhancing Potential of Alkyl-Maltosides.
AB  - The purpose of the present study was to investigate the interaction of intestinal
      permeation enhancers with lipid and surfactant components present in the milieu
      of the small intestine. Maltosides of different chain lengths (decyl-, dodecyl-,
      and tetradecyl-maltoside; DM, DDM, TDM, respectively) were used as examples of
      nonionic, surfactant-like permeation enhancers, and their effect on the
      permeation of FD4 across Caco-2 monolayers was monitored. To mimic the
      environment of the small intestine, modified versions of fasted and fed state
      simulated intestinal fluid (FaSSIFmod, FeSSIFmod6.5, respectively) were used in
      addition to standard transport media (TM). Compared to the buffer control, 0.5 mM
      DDM led to a 200-fold permeation enhancement of FD4 in TM. However, this was
      dramatically decreased in FaSSIFmod, where a concentration of 5 mM DDM was
      necessary in order to elicit a moderate, 4-fold, permeation enhancement. Its
      capacity to promote permeation was diminished further when FeSSIFmod6.5 was
      employed. Even when cells were exposed to a concentration of 5 mM, no significant
      permeation enhancement of FD4 was observed. Analogous effects were observed in
      the case of DM and TDM, with slight deviations on account of differences in their
      critical micelle concentration (CMC). This observation was corroborated by
      calculating the amount of maltoside monomer versus micellar bound maltoside in
      FaSSIFmod and FeSSIFmod6.5, which demonstrated a reduced amount of free monomer
      in these fluids. To evaluate the in vivo significance of our findings, DDM
      solutions in TM, FaSSIFmod, and FeSSIFmod6.5 were used for closed intestinal loop
      studies in rats. Consistent with the results found in in vitro permeation
      studies, these investigations illustrated the overwhelming impact of sodium
      taurocholate/lecithin micelles on the permeation enhancing effect of DDM. While
      DDM led to a 20-fold increase in FD4 bioavailability when it was applied in TM,
      no significant permeation enhancement was seen in FaSSIFmod/FeSSIFmod6.5.
      Collectively, these investigations highlight the importance of using biorelevant
      media when evaluating the potency of permeation enhancers. In doing so, this
      ensures improved correlations between in vitro and in vivo studies and thus
      enables an early and more accurate assessment of promising permeation enhancers. 

PMID- 25874853
TI  - Development of a Human Model for the Study of Effects of Hypoxia, Exercise, and
      Sildenafil on Cardiac and Vascular Function in Chronic Heart Failure.
AB  - BACKGROUND: Pulmonary hypertension is associated with poor outcome in patients
      with chronic heart failure (CHF) and may be a therapeutic target. Our aims were
      to develop a noninvasive model for studying pulmonary vasoreactivity in CHF and
      characterize sildenafil's acute cardiovascular effects. METHODS AND RESULTS: In a
      crossover study, 18 patients with CHF participated 4 times [sildenafil (2 * 20
      mg)/or placebo (double-blind) while breathing air or 15% oxygen] at rest and
      during exercise. Oxygen saturation (SaO2) and systemic vascular resistance were
      recorded. Left and right ventricular (RV) function and transtricuspid systolic
      pressure gradient (RVTG) were measured echocardiographically. At rest, hypoxia
      caused SaO2 (P = 0.001) to fall and RVTG to rise (5 +/- 4 mm Hg; P = 0.001).
      Sildenafil reduced SaO2 (-1 +/- 2%; P = 0.043), systemic vascular resistance (-87
      +/- 156 dyn.s.cm; P = 0.034), and RVTG (-2 +/- 5 mm Hg; P = 0.05). Exercise
      caused cardiac output (2.1 +/- 1.8 L/min; P < 0.001) and RVTG (19 +/- 11 mm Hg; P
      < 0.0001) to rise. The reduction in RVTG with sildenafil was not attenuated by
      hypoxia. The rise in RVTG with exercise was not substantially reduced by
      sildenafil. CONCLUSIONS: Sildenafil reduces SaO2 at rest while breathing air,
      this was not exacerbated by hypoxia, suggesting increased ventilation-perfusion
      mismatching due to pulmonary vasodilation in poorly ventilated lung regions.
      Sildenafil reduces RVTG at rest and prevents increases caused by hypoxia but not
      by exercise. This study shows the usefulness of this model to evaluate new
      therapeutics in pulmonary hypertension.

PMID- 25874854
TI  - Endothelial Soluble Factors Mediate Differentiation of Circulating Endothelial
      Precursors.
AB  - Although endothelial progenitor cells have been used in clinical trials with
      promising preliminary results, the mechanism by which these cells interact with
      vascular wall cells and ischemic tissues remains unclear. We have previously
      reported that human coronary artery endothelial cells cocultured with peripheral
      blood mononuclear cell (PBMC) can stimulate their early differentiation toward a
      pre-endothelial phenotype. This study was aimed to assess possible soluble
      factors, released from the coculture, and involved in endothelial progenitor cell
      differentiation. Among cytokines and chemokines measured by means of Milliplex
      assay, interleukin (IL)-6, IL-8, endothelial growth factor, and CCL-2 were
      released in cocultures, and those levels were significantly higher than that
      found in human coronary artery endothelial cells or in PBMCs alone. To check
      their involvement in PBMC differentiation, blocking experiments with neutralizing
      antibodies were performed. Flow cytometry analysis confirmed an impairment of
      PBMC differentiation toward a pre-endothelial phenotype when IL-6, IL-8 and with
      a lesser extent CCL-2 were blocked. These data add a new insight into the
      mechanisms by which endothelial precursors interact with vascular wall, thus
      suggesting future directions in understanding and treating ischemic injury. 

PMID- 25874855
TI  - Co-treatment of Pitavastatin and Dexamethasone Exacerbates the High-fat Diet
      induced Atherosclerosis in apoE-deficient Mice.
AB  - Activation of macrophage adipocyte fatty acid-binding protein (FABP4) induces
      development of atherosclerosis in animal models. We previously reported that
      statin inhibited while dexamethasone activated macrophage FABP4 expression.
      However, co-treatment of macrophages with statin and dexamethasone induced FABP4
      expression in a synergistic manner, which implies that this co-treatment may
      exacerbate high-fat diet (HFD)-induced atherosclerosis. In this study, we fed
      apoE-deficient (apoE) mice with HFD or HFD containing dexamethasone or
      pitavastatin or both for 16 weeks. Compared with HFD alone, pitavastatin or
      dexamethasone had little effect on lesions in both en face aortas and aortic root
      cross sections. However, the co-treatment exacerbated HFD-induced lesions. In
      addition, the co-treatment decreased collagen content and disturbed the integrity
      of lesion caps. Both serum total cholesterol and LDL cholesterol levels were
      reduced by pitavastatin and increased by dexamethasone, respectively. However,
      the co-treatment had little effect on both total cholesterol and LDL cholesterol
      levels, indicating that the exacerbation of lesions is independent of total
      cholesterol or LDL cholesterol levels. FABP4 expression in aortic lesion area was
      significantly induced by the co-treatment, suggesting that activation of FABP4
      expression is a main contributor to lesions. In conclusion, our study
      demonstrates that co-treatment of pitavastatin and dexamethasone exacerbates HFD
      induced atherosclerosis and defines a potential risk to use the dual treatment
      for patients in clinics. 

PMID- 25874856
TI  - Fibroblastic Transformation of Corneal Keratocytes by Rac Inhibition is Modulated
      by Extracellular Matrix Structure and Stiffness.
AB  - The goal of this study was to investigate how alterations in extracellular matrix
      (ECM) biophysical properties modulate corneal keratocyte phenotypes in response
      to specific wound healing cytokines and Rho GTPases. Rabbit corneal keratocytes
      were plated within standard collagen matrices (2.5 mg/mL) or compressed collagen
      matrices (~100 mg/mL) and cultured in serum-free media, PDGF BB, IGF, FGF2 or
      TGFbeta1, with or without the Rac1 inhibitor NSC23766 and/or the Rho kinase
      inhibitor Y-27632. After 1 to 4 days, cells were labeled for F-actin and imaged
      using confocal microscopy. Keratocytes within standard collagen matrices (which
      are highly compliant) maintained a dendritic phenotype following culture in serum
      free media, PDGF, IGF and FGF, but developed stress fibers in TGFbeta1.
      Keratocytes within compressed collagen (which has high stiffness and low
      porosity) maintained a dendritic phenotype following culture in serum-free media,
      PDGF and IGF, but developed stress fibers in both FGF and TGFbeta1. The Rac
      inhibitor had no significant impact on growth factor responses in compliant
      matrices. Within compressed collagen matrices however, the Rac inhibitor induced
      fibroblastic transformation in serum-free media, PDGF and IGF. Fibroblast and
      myofibroblast transformation was blocked by Rho kinase inhibition. Overall,
      keratocyte growth factor responses appear to be regulated by both the interplay
      between Rho and Rac signaling, and the structural and mechanical properties of
      the ECM. 

PMID- 25874857
TI  - Ability of immunodiagnostic tests to differentiate between dogs naturally
      infected with Leishmania infantum and Leishmune((r))-vaccinated dogs.
AB  - Visceral leishmaniasis (VL) is a serious chronic disease with a lethality rate of
      up to 10% in humans. In urban areas of Brazil, dogs are the main reservoirs of
      the etiological agent (Leishmania infantum) of VL, and the Brazilian Ministry of
      Health recommends the euthanasia of animals that are seropositive in both the
      immunochromatographic dual path platform rapid test (DPP((r)); Bio-Manguinhos)
      and the enzyme-linked immunosorbent assay (ELISA) with an L. major-like antigen
      (Bio-Manguinhos). Vaccination is an additional tool in the control of canine VL,
      but the use of Leishmune((r)) (Zoetis Industria de Produtos Veterinarios, Sao
      Paulo, SP, Brazil), which contains the fucose mannose ligand (FML) isolated from
      L. donovani, is not currently recommended by the Brazilian Ministry of Health
      because vaccinated animals may exhibit positive serology and there are
      reservations regarding the efficacy of the vaccine. The aims of the present study
      were: (i) to verify the abilities of the fast agglutination screening test
      (FAST), the direct agglutination test (DAT), the indirect fluorescent-antibody
      test (IFAT), the DPP rapid test, and ELISA tests with L. major-like and FML
      antigens to differentiate between L. infantum-infected and Leishmune((r))
      vaccinated dogs, and (ii) to analyze the sensitivities and specificities of the
      different methods. The reactivities to these tests of Leishmune((r))-vaccinated
      dogs (n = 71), asymptomatic (n = 20) and symptomatic (n = 20) naturally infected
      dogs, and unvaccinated healthy control dogs (n = 5) were compared. None of the
      Leishmune((r))-vaccinated dogs tested seropositive in FAST and DAT, although one
      dog was reactive to DPP and four dogs to ELISA/L. major-like and IFAT tests.
      While 69 (97%) of vaccinated dogs reacted to ELISA/FML, only one was seropositive
      in both ELISA/L. major-like and IFAT tests. Individually, all immunodiagnostic
      tests presented high specificities and positive likelihood ratios (LR+), and high
      specificity values were obtained when the tests were considered in pairs.
      However, sensitivity and LR- values were low for ELISA/L. major-like and IFAT
      tests individually, and for all pair combinations of tests except for FAST with
      DPP.

PMID- 25874858
TI  - Effects of reconstruction of a pre-European vertebrate assemblage on ground
      dwelling arachnids in arid Australia.
AB  - Species loss can result in changes in assemblage structure and ecosystem function
      through ecological cascades. Australian vertebrate assemblages changed
      significantly following European colonisation, which resulted in the
      establishment of invasive vertebrates and the loss of native marsupials, many of
      which consume invertebrates. Conservation focusses on the removal of invasive
      carnivores and the reintroduction of regionally extinct species to fenced sites,
      resulting in what could be considered a reconstruction of pre-European vertebrate
      assemblages. In semi-arid Australian spinifex mallee ecosystems, we asked: (1)
      what is the effect of reconstructed pre-European vertebrate assemblages on native
      arachnid assemblages? and (2) what direct or indirect mechanisms (predation,
      disturbance and/or competition) could plausibly be responsible for these effects?
      We compared sites with reconstructed vertebrate assemblages with paired control
      sites. Arachnids were sampled using pitfall trapping and direct searching.
      Hypotheses regarding mechanisms were tested using scat analysis (predation) and
      by comparing burrow depth (disturbance) and scorpion mass (competition) between
      control and reconstructed sites. The dominant dune scorpion, Urodacus yaschenkoi,
      was less abundant and a wolf spider (Lycosa gibsoni species group) more abundant
      in reconstructed sites. Differences in spider assemblage composition were
      marginally non-significant. Scat analysis confirmed native vertebrate predation
      on scorpions and we found no evidence that competition or disturbance affected
      scorpions. We, thus, suggest that changes in spider assemblages may have resulted
      from ecological cascades via decreases in dune scorpions. The loss of omnivorous
      mammals and other changes associated with the invasion of carnivores may,
      therefore, have had broad-reaching consequences for native arachnid assemblages
      in Australian ecosystems. 

PMID- 25874860
TI  - Total variation with overlapping group sparsity for image deblurring under
      impulse noise.
AB  - The total variation (TV) regularization method is an effective method for image
      deblurring in preserving edges. However, the TV based solutions usually have some
      staircase effects. In order to alleviate the staircase effects, we propose a new
      model for restoring blurred images under impulse noise. The model consists of an
      l1-fidelity term and a TV with overlapping group sparsity (OGS) regularization
      term. Moreover, we impose a box constraint to the proposed model for getting more
      accurate solutions. The solving algorithm for our model is under the framework of
      the alternating direction method of multipliers (ADMM). We use an inner loop
      which is nested inside the majorization minimization (MM) iteration for the
      subproblem of the proposed method. Compared with other TV-based methods,
      numerical results illustrate that the proposed method can significantly improve
      the restoration quality, both in terms of peak signal-to-noise ratio (PSNR) and
      relative error (ReE). 

PMID- 25874859
TI  - Natural light exposure, sleep and depression among day workers and shiftworkers
      at arctic and equatorial latitudes.
AB  - OBJECTIVES: This study aimed to investigate the relationship between individual
      natural light exposure, sleep need, and depression at two latitudes, one extreme
      with a few hours of light per day during winter, and the other with equal hours
      of light and darkness throughout the year. METHODS: This cross-sectional study
      included a sample of Brazilian workers (Equatorial, n = 488 workers) and a
      Swedish sample (Arctic, n = 1,273). RESULTS: The reported mean total natural
      light exposure per 4-week cycle differed significantly between the Equatorial and
      Arctic regions. However, shiftworkers from both sites reported similar hours of
      natural light exposure. Short light exposure was a predictor for insufficient
      sleep. CONCLUSION: Reduced exposure to natural light appears to increase the
      perception of obtaining insufficient sleep. Arctic workers were more prone to
      develop depression than Equatorial workers.

PMID- 25874861
TI  - Numerical simulation and structural optimization of the inclined oil/water
      separator.
AB  - Improving the separation efficiency of the inclined oil/water separator, a new
      type of gravity separation equipment, is of great importance. In order to obtain
      a comprehensive understanding of the internal flow field of the separation
      process of oil and water within this separator, a numerical simulation based on
      Euler multiphase flow analysis and the realizable k-epsilon two equation
      turbulence model was executed using Fluent software. The optimal value ranges of
      the separator's various structural parameters used in the numerical simulation
      were selected through orthogonal array experiments. A field experiment on the
      separator was conducted with optimized structural parameters in order to validate
      the reliability of the numerical simulation results. The research results
      indicated that the horizontal position of the dispenser, the hole number, and the
      diameter had significant effects on the oil/water separation efficiency, and that
      the longitudinal position of the dispenser and the position of the weir plate had
      insignificant effects on the oil/water separation efficiency. The optimal
      structural parameters obtained through the orthogonal array experiments resulted
      in an oil/water separation efficiency of up to 95%, which was 4.996% greater than
      that realized by the original structural parameters. 

PMID- 25874862
TI  - Association of dialysis with the risks of cancers.
AB  - BACKGROUND: To increase the survival span after dialysis in patients with end
      stage renal disease (ESRD), identifying specific cancer risks is crucial in the
      cancer screening of these patients. The aim of this study was to investigate the
      risks of various cancers in an incident dialysis group in comparison with a non
      dialysis group. METHOD: We conducted a nationwide cohort study by using data from
      the Taiwan National Health Insurance Research Database. Patients who initially
      received long-term dialysis between January 1997 and December 2004, were selected
      and defined as the dialysis group and were matched with the non-dialysis patients
      (control group) according to age, sex, and index year. Competing risk analysis
      was used to estimate cumulative incidence and subdistribution hazard ratios
      (SHRs) of the first cancer occurrence. RESULTS: After consideration for the
      competing risk of mortality, the dialysis group showed a significantly higher 7
      year cancer incidence rate than did the control group (6.4%; 95% confidence
      interval [CI], 6.0%-6.7% vs 1.7%; 95% CI, 1.4%-2.1%; P <0.001).The modified Cox
      proportional hazard model revealed that the dialysis group had significantly
      association with increased risks for all cancers (SHR, 3.43; 95% CI, 3.02-3.88).
      The risk of cancers was dominated in younger and female patients. Specific cancer
      risks were significantly higher in the dialysis group particularly in the
      development of oral, colorectal, liver, blood, breast, renal, upper urinary
      tract, and bladder cancer than in the control group. Multivariable stratified
      analyses confirmed the association between long-term dialysis and cancer in all
      subgroups of patients. CONCLUSIONS: Dialysis is associated with a higher risk of
      cancer in patients with ESRD. However, cancer screening in ESRD population should
      be a selective approach, based on individual patient health condition and life
      expectancy.

PMID- 25874863
TI  - Correction: quantitative analysis of ligand-EGFR interactions: a platform for
      screening targeting molecules.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0116610.]. 

PMID- 25874864
TI  - Quantitative characterization of non-classic polarization of cations on clay
      aggregate stability.
AB  - Soil particle interactions are strongly influenced by the concentration, valence
      and ion species and the pH of the bulk solution, which will also affect aggregate
      stability and particle transport. In this study, we investigated clay aggregate
      stability in the presence of different alkali ions (Li+, Na+, K+, and Cs+) at
      concentrations from10-5 to 10-1 mol L-1. Strong specific ion effects on clay
      aggregate stability were observed, and showed the order Cs+>K+>Na+>Li+. We found
      that it was not the effects of ion size, hydration, and dispersion forces in the
      cation-surface interactions but strong non-classic polarization of adsorbed
      cations that resulted in these specific effects. In this study, the non-classic
      dipole moments of each cation species resulting from the non-classic polarization
      were estimated. By comparing non-classic dipole moments with classic values, the
      observed dipole moments of adsorbed cations were up to 104 times larger than the
      classic values for the same cation. The observed non-classic dipole moments
      sharply increased with decreasing electrolyte concentration. We conclude that
      strong non-classic polarization could significantly suppress the thickness of the
      diffuse layer, thereby weakening the electric field near the clay surface and
      resulting in improved clay aggregate stability. Even though we only demonstrated
      specific ion effects on aggregate stability with several alkali ions, our results
      indicate that these effects could be universally important in soil aggregate
      stability. 

PMID- 25874865
TI  - MLK3 phophorylates AMPK independently of LKB1.
AB  - Emerging evidence has shown that cellular energy metabolism is regulated by the
      AMPK and MLK3-JNK signaling pathways, but the functional link between them
      remains to be determined. The present study aimed to explore the crosstalk
      between MLK3 and AMPK. We found that both JNK and AMPK were phosphorylated at
      their activation sites by TNF-alpha, Anisomycin, H2O2 and sorbitol.
      Interestingly, sorbitol stimulated phosphorylation of AMPK at T172 in LKB1
      deficient cells. Following the screening of more than 100 kinases, we identified
      that MLK3 induced phosphorylation of AMPK at T172. Our in vitro analysis further
      revealed that MLK3-mediated phosphorylation of AMPK at T172 was independent of
      AMP, but addition of AMP caused a mobility shift of AMPK, an indication of
      autophosphorylation, suggesting that AMP binding and phosphorylation of T172
      leads to maximal activation of AMPK. GST-pull down assays showed a direct
      interaction between AMPKalpha1 subunit and MLK3. Altogether, our results indicate
      that MLK3 serves as a common upstream kinase of AMPK and JNK and functions as a
      direct upstream kinase for AMPK independent of LKB1. 

PMID- 25874867
TI  - Fasting plasma glucose as initial screening for diabetes and prediabetes in irish
      adults: The Diabetes Mellitus and Vascular health initiative (DMVhi).
AB  - OBJECTIVE: Type 2 diabetes has a long pre clinical asymptomatic phase. Early
      detection may delay or arrest disease progression. The Diabetes Mellitus and
      Vascular health initiative (DMVhi) was initiated as a prospective longitudinal
      cohort study on the prevalence of undiagnosed Type 2 diabetes and prediabetes,
      diabetes risk and cardiovascular risk in a cohort of Irish adults aged 45-75
      years. RESEARCH DESIGN AND METHODS: Members of the largest Irish private health
      insurance provider aged 45 to 75 years were invited to participate in the study.
      EXCLUSION CRITERIA: already diagnosed with diabetes or taking oral hypoglycaemic
      agents. Participants completed a detailed medical questionnaire, had weight,
      height, waist and hip circumference and blood pressure measured. Fasting blood
      samples were taken for fasting plasma glucose (FPG). Those with FPG in the
      impaired fasting glucose (IFG) range had a 75gm oral glucose tolerance test
      performed. RESULTS: 122,531 subjects were invited to participate. 29,144 (24%)
      completed the study. The prevalence of undiagnosed diabetes was 1.8%, of impaired
      fasting glucose (IFG) was 7.1% and of impaired glucose tolerance (IGT) was 2.9%.
      Dysglycaemia increased among those aged 45-54, 55-64 and 65-75 years in both
      males (10.6%, 18.5%, 21.7% respectively) and females (4.3%, 8.6%, 10.9%
      respectively). Undiagnosed T2D, IFG and IGT were all associated with gender, age,
      blood pressure, BMI, abdominal obesity, family history of diabetes and
      triglyceride levels. Using FPG as initial screening may underestimate the
      prevalence of T2D in the study population. CONCLUSIONS: This study is the largest
      screening study for diabetes and prediabetes in the Irish population. Follow up
      of this cohort will provide data on progression to diabetes and on cardiovascular
      outcomes.

PMID- 25874866
TI  - Reducing frequent visits to the emergency department: a systematic review of
      interventions.
AB  - OBJECTIVE: The objective of this study was to establish the effectiveness of
      interventions to reduce frequent emergency department (ED) use among a general
      adult high ED-use population. METHODS: Systematic review of the literature from
      1950-January 2015. Studies were included if they: had a control group (controlled
      trials or comparative cohort studies), were set in an ED or acute care facility,
      and examined the impact of an intervention to reduce frequent ED use in a general
      adult population. Studies reporting non-original data or focused on a specific
      patient population were excluded. Study design, patient population, intervention,
      the frequency of ED visits, and costs of frequent ED use and/or interventions
      were extracted and narratively synthesized. RESULTS: Among 17 included articles,
      three intervention categories were identified: case management (n = 12),
      individualized care plans (n = 3), and information sharing (n = 2). Ten studies
      examining case management reported reductions in mean (-0.66 to -37) or median (
      0.1 to -20) number of ED visits after 12-months; one study reported an increase
      in mean ED visits (+2.79); and one reported no change. Of these, 6 studies also
      reported reduced hospital costs. Only 1 study evaluating individualized care
      plans examined ED utilization and found no change in median ED visits post
      intervention. Costs following individualized care plans were also only evaluated
      in 1 study, which reported savings in hospital costs of $742/patient. Evidence
      was mixed regarding information sharing: 1 study reported no change in mean ED
      visits and did not examine costs; whereas the other reported a decrease in mean
      ED visits (-16.9) and ED cost savings of $15,513/patient. CONCLUSIONS: The impact
      of all three frequent-user interventions was modest. Case management had the most
      rigorous evidence base, yielded moderate cost savings, but with variable
      reductions in ED use. Future studies evaluating non-traditional interventions,
      tailoring to patient subgroups or socio-cultural contexts, are warranted.

PMID- 25874868
TI  - Impaired tilt perception in Parkinson's disease: a central vestibular integration
      failure.
AB  - INTRODUCTION: Impaired balance control is a hallmark symptom in Parkinson's
      disease (PD). Altered sensory-motor integration contributes to the deficiency. We
      aimed to determine whether impaired vestibular signal processing added to the
      disorder. We exposed patients (N = 11; 68+/-6y) and age-matched healthy subjects
      (hS: N = 19; 65+/-11y) on a motion platform in complete darkness to two
      consecutive forward tilt movements (12 series; N = 24; overall 288 trials) and
      asked them to indicate which tilt was perceived larger. By combing tilt movements
      with translations we manipulated vestibular sensory input in order to investigate
      whether putative impairment resulted from a deficiency of the sensory organs
      (semicircular canals in 'single-SCC-cue-condition', otoliths in 'single-OT-cue
      condition') themselves or to a sensory integration failure ('multi-cue
      condition'). RESULTS: Tilt discrimination in the multi-cue-condition was inferior
      in patients compared to hS (p = 0.02). No significant differences between the two
      groups were found for both single-cue-conditions. Comparison of multi-cue
      condition with a prediction resulting from the combination of both single-cue
      conditions by optimal observer theory revealed that patients (p = 0.04), in
      contrast to hS, failed to efficiently combine SCC and OT information to improve
      tilt perception. CONCLUSION: We found that PD patients distinguished forward
      tilts less precise than hS, suggesting impaired vestibular perception. Tilt
      discrimination in patients, moreover, did not improve as much as in hS in
      conditions where both SCC and OT information was available compared to conditions
      where only SCC or OT cues were activated. The latter provides evidence that tilt
      misperception in PD most likely results from an integration failure of vestibular
      signals.

PMID- 25874869
TI  - Shade avoidance components and pathways in adult plants revealed by phenotypic
      profiling.
AB  - Shade from neighboring plants limits light for photosynthesis; as a consequence,
      plants have a variety of strategies to avoid canopy shade and compete with their
      neighbors for light. Collectively the response to foliar shade is called the
      shade avoidance syndrome (SAS). The SAS includes elongation of a variety of
      organs, acceleration of flowering time, and additional physiological responses,
      which are seen throughout the plant life cycle. However, current mechanistic
      knowledge is mainly limited to shade-induced elongation of seedlings. Here we use
      phenotypic profiling of seedling, leaf, and flowering time traits to untangle
      complex SAS networks. We used over-representation analysis (ORA) of shade
      responsive genes, combined with previous annotation, to logically select 59 known
      and candidate novel mutants for phenotyping. Our analysis reveals shared and
      separate pathways for each shade avoidance response. In particular, auxin pathway
      components were required for shade avoidance responses in hypocotyl, petiole, and
      flowering time, whereas jasmonic acid pathway components were only required for
      petiole and flowering time responses. Our phenotypic profiling allowed discovery
      of seventeen novel shade avoidance mutants. Our results demonstrate that logical
      selection of mutants increased success of phenotypic profiling to dissect complex
      traits and discover novel components. 

PMID- 25874870
TI  - Proteomic profiling of SupT1 cells reveal modulation of host proteins by HIV-1
      Nef variants.
AB  - Nef is an accessory viral protein that promotes HIV-1 replication, facilitating
      alterations in cellular pathways via multiple protein-protein interactions. The
      advent of proteomics has expanded the focus on better identification of novel
      molecular pathways regulating disease progression. In this study, nef was
      sequenced from randomly selected patients, however, sequence variability
      identified did not elicited any specific mutation that could have segregated HIV
      1 patients in different stages of disease progression. To explore the difference
      in Nef functionality based on sequence variability we used proteomics approach.
      Proteomic profiling was done to compare the effect of Nef variants in host cell
      protein expression. 2DGE in control and Nef transfected SupT1 cells demonstrated
      several differentially expressed proteins. Fourteen protein spots were detected
      with more than 1.5 fold difference. Significant down regulation was seen in six
      unique protein spots in the Nef treated cells. Proteins were identified as
      Cyclophilin A, EIF5A-1 isoform B, Rho GDI 1 isoform a, VDAC1, OTUB1 and alpha
      enolase isoform 1 (ENO1) through LC-MS/MS. The differential expression of the 6
      proteins was analyzed by Real time PCR, Western blotting and Immunofluorescence
      studies with two Nef variants (RP14 and RP01) in SupT1 cells. There was
      contrasting difference between the effect of these Nef variants upon the
      expression of these six proteins. Downregulation of alpha-enolase (ENO1), VDAC1
      and OTUB1 was more significant by Nef RP01 whereas Cyclophilin A and RhoGDI were
      found to be more downregulated by Nef RP14. This difference in Nef variants upon
      host protein expression was also studied through a site directed mutant of Nef
      RP01 (55AAAAAAA61) and the effect was found to be reversed. Deciphering the role
      of these proteins mediated by Nef variants will open a new avenue of research in
      understanding Nef mediated pathogenesis. Overall study determines modulation of
      cellular protein expression in T cells by HIV-1 Nef variants. 

PMID- 25874871
TI  - Association of urinary metal profiles with altered glucose levels and diabetes
      risk: a population-based study in China.
AB  - BACKGROUND: Elevated heavy metals and fasting plasma glucose (FPG) levels were
      both associated with increased risk of cardiovascular diseases. However, studies
      on the associations of heavy metals and essential elements with altered FPG and
      diabetes risk were limited or conflicting. The objective of this study was to
      evaluate the potential associations of heavy metals and essential trace elements
      with FPG and diabetes risk among general Chinese population. METHODS: We
      conducted a cross-sectional study to investigate the associations of urinary
      concentrations of 23 metals with FPG, impaired fasting glucose (IFG) and diabetes
      among 2242 community-based Chinese adults in Wuhan. We used the false discovery
      rate (FDR) method to correct for multiple hypothesis tests. RESULTS: After
      adjusting for potential confounders, urinary aluminum, titanium, cobalt, nickel,
      copper, zinc, selenium, rubidium, strontium, molybdenum, cadmium, antimony,
      barium, tungsten and lead were associated with altered FPG, IFG or diabetes risk
      (all P< 0.05); arsenic was only dose-dependently related to diabetes (P< 0.05).
      After additional adjustment for multiple testing, titanium, copper, zinc,
      selenium, rubidium, tungsten and lead were still significantly associated with
      one or more outcomes (all FDR-adjusted P< 0.05). CONCLUSIONS: Our results suggest
      that multiple metals in urine are associated with FPG, IFG or diabetes risk.
      Because the cross-sectional design precludes inferences about causality, further
      prospective studies are warranted to validate our findings.

PMID- 25874873
TI  - Correction: Microporous dermal-mimetic electrospun scaffolds pre-seeded with
      fibroblasts promote tissue regeneration in full-thickness skin wounds.

PMID- 25874872
TI  - Comparison of methods for in-house screening of HLA-B*57:01 to prevent abacavir
      hypersensitivity in HIV-1 care.
AB  - Abacavir is a nucleoside reverse transcriptase inhibitor used as part of
      combination antiretroviral therapy in HIV-1-infected patients. Because this drug
      can cause a hypersensitivity reaction that is correlated with the presence of the
      HLA-B*57:01 allotype, screening for the presence of HLA-B*57:01 is recommended
      before abacavir initiation. Different genetic assays have been developed for HLA
      B*57:01 screening, each with specific sensitivity, turnaround time and assay
      costs. Here, a new real-time PCR (qPCR) based analysis is described and compared
      to sequence specific primer PCR with capillary electrophoresis (SSP PCR CE) on
      149 patient-derived samples, using sequence specific oligonucleotide
      hybridization combined with high resolution SSP PCR as gold standard. In addition
      to these PCR based methods, a complementary approach was developed using flow
      cytometry with an HLA-B17 specific monoclonal antibody as a pre-screening assay
      to diminish the number of samples for genetic testing. All three assays had a
      maximum sensitivity of >99. However, differences in specificity were recorded,
      i.e. 84.3%, 97.2% and >99% for flow cytometry, qPCR and SSP PCR CE respectively.
      Our data indicate that the most specific and sensitive of the compared methods is
      the SSP PCR CE. Flow cytometry pre-screening can substantially decrease the
      number of genetic tests for HLA-B*57:01 typing in a clinical setting. 

PMID- 25874874
TI  - Midwifery care and patient-provider communication in maternity decisions in the
      United States.
AB  - To characterize reasons women chose midwives as prenatal care providers and to
      measure the relationship between midwifery care and patient-provider
      communication in the U.S. CONTEXT: Retrospective analysis of data from a
      nationally-representative survey of women who gave birth in 2011-2012 to a single
      newborn in a U.S. hospital (n = 2,400). We used multivariate logistic regression
      models to characterize women who received prenatal care from a midwife, to
      describe the reasons for this choice, and to examine the association between
      midwife-led prenatal care and women's reports about communication. Preference for
      a female clinician and having a particular clinician assigned was associated with
      higher odds of midwifery care (AOR = 2.65, 95 % CI 1.70, 4.14 and AOR = 1.63, 95
      % CI 1.04, 2.58). A woman with midwifery care had lower odds of reporting that
      she held back questions because her preference for care was different from her
      provider's recommendation (AOR = 0.46, 95 % CI 0.23, 0.89) or because she did not
      want to be perceived as difficult (AOR = 0.48, 95 % CI 0.28, 0.81). Women
      receiving midwifery care also had lower odds of reporting that the provider used
      medical words were hard for them to understand (AOR = 0.58, 95 % CI 0.37, 0.91)
      and not feeling encouraged to discuss all their concerns (AOR = 0.54, 95 % CI
      0.34, 0.89). Women whose prenatal care was provided by midwives report better
      communication compared with those cared for by other types of clinicians. Systems
      level interventions, such as assigning a clinician, may improve access to
      midwifery care and the associated improvements in patient-provider communication
      in maternity care.

PMID- 25874875
TI  - The Hidden Costs of a Free Caesarean Section Policy in West Africa (Kayes Region,
      Mali).
AB  - The fee exemption policy for EmONC in Mali aims to lower the financial barrier to
      care. The objective of the study was to evaluate the direct and indirect expenses
      associated with caesarean interventions performed in EmONC and the factors
      associated with these expenses. Data sampling followed the case control approach
      used in the large project (deceased and near-miss women). Our sample consisted of
      a total of 190 women who underwent caesarean interventions. Data were collected
      from the health workers and with a social approach by administering
      questionnaires to the persons who accompanied the woman. Household socioeconomic
      status was assessed using a wealth index constructed with a principal component
      analysis. The factors significantly associated with expenses were determined
      using multivariate linear regression analyses. Women in the Kayes region spent on
      average 77,017 FCFA (163 USD) for a caesarean episode in EmONC, of which 70 % was
      for treatment. Despite the caesarean fee exemption, 91 % of the women still paid
      for their treatment. The largest treatment-related direct expenses were for
      prescriptions, transfusion, antibiotics, and antihypertensive medication. Near
      misses, women who presented a hemorrhage or an infection, and/or women living in
      rural areas spent significantly more than the others. Although abolishing fees of
      EmONC in Mali plays an important role in reducing maternal death by increasing
      access to caesarean sections, this paper shows that the fee policy did not
      benefit to all women. There are still barriers to EmONC access for women of the
      lowest socio-economic group. These included direct expenses for drugs
      prescription, treatment and indirect expenses for transport and food.

PMID- 25874876
TI  - The Association Between Medicaid Coverage for Children and Parents Persists: 2002
      2010.
AB  - To assess the association between a child's and their parent's public health
      insurance status during a time when children had access to coverage independent
      of policies that impacted adults' access. Secondary data from the Oregon Health
      Plan (OHP) [Oregon's Medicaid and Children's Health Insurance Programs] for
      families with at least one parent and one child with OHP coverage at any time
      during the study period (2002-2010). We linked children to their parents in the
      OHP data set and examined longitudinal associations between the coverage patterns
      for children and their parents, controlling for several demographic and economic
      confounders. We tested for differences in the strength of associations in monthly
      coverage status in five time periods throughout the nine-year study period. The
      odds of a child being insured by the OHP in months in which at least one parent
      had OHP coverage were significantly higher than among children whose parents were
      not enrolled at that time. Children with at least one parent who maintained or
      gained OHP coverage in a given month had a much higher probability of being
      enrolled in the OHP in that month, compared to children who had no covered
      parents in the given month or the month prior. Despite implementation of policies
      that differentially affected eligibility requirements for children and adults,
      strong associations persisted between coverage continuity for parents and
      children enrolled in Oregon public health insurance programs.

PMID- 25874877
TI  - Do Physical Activity Patterns Across the Lifecourse Impact Birth Outcomes?
AB  - The significant impact of physical activity during, or immediately prior to
      pregnancy on a range of pregnancy and birth outcomes has been established.
      However, lifecourse theory posits that the antecedents of poor outcomes occur
      across a larger trajectory of time. The objective of this study was to examine
      whether physical activity patterns over the lifecourse impact birth outcomes. The
      sample (n = 1,713) was derived from Waves I, III, and IV of the National
      Longitudinal Study of Adolescent Health and limited to women who had their first,
      singleton live birth between Waves III and IV; respondents who had missing data
      were excluded. Outcome variables included preterm birth (<37 weeks) and low birth
      weight (<5.5 pounds). Physical activity was categorized as follows: long-term
      physically active (active at Waves I and III); short-term physically active
      (active at only Wave I or III); and not physically active (not active at Waves I
      and III). Survey-weighted logistic regression controlled for socio-demographic
      and established predictors of poor birth outcomes. Women categorized as long-term
      physically active had lower rates of preterm births (12.2 vs. 18.7 %) and low
      birth weight (9.1 vs. 11.1 %) compared to women categorized as not physically
      active. However, when controlling for covariates, adjusted analysis revealed that
      physical activity consistency only predicted preterm birth (aOR = 0.55, 95 % CI =
      0.33-0.91). Findings suggest that physical activity patterns across the
      lifecourse may decrease risk of preterm birth. Implications include efforts
      supporting patterns of physical activity over longer periods of time prior to
      pregnancy.

PMID- 25874879
TI  - Individual and Area Level Factors Associated with Prenatal, Delivery, and
      Postnatal Care in Pakistan.
AB  - This research examines individual and area level factors associated with maternal
      health care utilization in Pakistan. The 2012-2013 Pakistan Demographic and
      Health Surveys data was used to model five outcomes: prenatal care within the
      first trimester, four plus prenatal visits, birth attendance by a skilled
      attendant, birth in a medical facility, and receipt of postnatal care. Less than
      half of births were to mothers receiving prenatal care in the first trimester,
      and approximately 57 % had trained personnel at delivery. Over half were born to
      mothers who received postnatal care. Evidence was found to support the positive
      effect of individual level variables, education and wealth, on the utilization of
      maternal health care across all five measures. Although, this study did not find
      unilateral differences between women residing in rural and urban settings, rural
      women were found to have lower odds of utilizing prenatal services as compared to
      mothers in urban environments. Additionally, women who cited distance as a
      barrier, had lower odds of receiving postnatal health care, but still engaged in
      prenatal services and often had a skilled attendant present at delivery. The odds
      of utilizing prenatal care increased when women resided in an area where prenatal
      utilization was high, and this variability was found across measures across
      provinces. The results found in this paper highlight the uneven progress made
      around improving prenatal, delivery, and postnatal care in Pakistan; disparities
      persist which may be attributed to factors both at the individual and community
      level, but may be addressed through a consorted effort to change national policy
      around women's health which should include the promotion of evidence based
      interventions such as incentivizing health care workers, promoting girls'
      education, and improving transportation options for pregnant women and recent
      mothers with the intent of ultimately lowering the Maternal Mortality Rate as
      recommended in the U.N.'s Millennium Development Goal 5. 

PMID- 25874878
TI  - Feasibility and Initial Efficacy Evaluation of a Community-Based Cognitive
      Behavioral Lifestyle Intervention to Prevent Excessive Weight Gain During
      Pregnancy in Latina Women.
AB  - About 48 % of US women gain more weight during pregnancy than recommended by the
      Institute of Medicine (IOM). Excessive gestational weight gain is a major risk
      factor for obesity in both women and offspring over their lifetimes, and should
      be avoided. This study was designed to test the feasibility and initial efficacy
      of a prenatal behavioral intervention in a sample of low-income, predominantly
      Latina women. The intervention was delivered in groups of 8-10 women in a
      community recreation center, and structured to reduce the proportion of women who
      gained weight in excess of IOM guidelines. Recruitment targets were met in 3
      months: 135 pregnant women (>10 and <28 weeks) were randomly assigned to receive
      a 12-week intervention (n = 68) or usual care (n = 67). Retention rate was 81 %.
      On average, women attended 4 of 12 group sessions, and each session had 4 of the
      8-10 assigned participants in attendance. Initial efficacy analyses were based on
      87 women. Compared to usual care, fewer normal-weight women in the intervention
      exceeded IOM recommendations (47.1 % usual care vs. 6.7 % intervention; absolute
      difference 40.4 %; p = .036). Recommendations for recruitment, retention, and
      delivery are discussed. A community-based cognitive-behavioral lifestyle
      intervention during pregnancy was feasible in a hard-to-reach, high-risk
      population of low-income Latina women, and showed efficacy in preventing
      excessive gestational weight gain. Due to frequently changing work schedules,
      strategies are needed to either increase attendance at group sessions (e.g.,
      within a group prenatal care format) or to build core skills necessary for
      behavior change through other modalities.

PMID- 25874880
TI  - The 50s cliff: a decline in perceptuo-motor learning, not a deficit in visual
      motion perception.
AB  - Previously, we measured perceptuo-motor learning rates across the lifespan and
      found a sudden drop in learning rates between ages 50 and 60, called the "50s
      cliff." The task was a unimanual visual rhythmic coordination task in which
      participants used a joystick to oscillate one dot in a display in coordination
      with another dot oscillated by a computer. Participants learned to produce a
      coordination with a 90 degrees  relative phase relation between the dots.
      Learning rates for participants over 60 were half those of younger participants.
      Given existing evidence for visual motion perception deficits in people over 60
      and the role of visual motion perception in the coordination task, it remained
      unclear whether the 50s cliff reflected onset of this deficit or a genuine
      decline in perceptuo-motor learning. The current work addressed this question.
      Two groups of 12 participants in each of four age ranges (20s, 50s, 60s, 70s)
      learned to perform a bimanual coordination of 90 degrees  relative phase. One
      group trained with only haptic information and the other group with both haptic
      and visual information about relative phase. Both groups were tested in both
      information conditions at baseline and post-test. If the 50s cliff was caused by
      an age dependent deficit in visual motion perception, then older participants in
      the visual group should have exhibited less learning than those in the haptic
      group, which should not exhibit the 50s cliff, and older participants in both
      groups should have performed less well when tested with visual information.
      Neither of these expectations was confirmed by the results, so we concluded that
      the 50s cliff reflects a genuine decline in perceptuo-motor learning with aging,
      not the onset of a deficit in visual motion perception. 

PMID- 25874882
TI  - iTRAQ-based quantitative proteomic analysis on S100 calcium binding protein A2 in
      metastasis of laryngeal cancer.
AB  - Laryngeal cancer is the most frequent neoplasm in the head and neck region, with
      the vast majority of tumors originating from squamous cells. The survival rate of
      patients with laryngeal cancer has not improved substantially over the past 25
      years. To acquire further knowledge regarding the molecules responsible for
      laryngeal cancer oncogenesis and, in turn, to improve target therapy iTRAQ and
      mass spectrometry analysis were utilized to detect differences in protein
      expression from 15 paired laryngeal cancer and adjacent non-cancerous tissue
      samples. Using mass spectrometry analysis, the expression levels of 100 proteins
      in laryngeal cancer samples were distinct from the non-tumor, non-cancerous
      samples. Further validation of the differentially expressed proteins S100A2,
      KRT16, FGB and HSPB1 were carried out using quantitative real-time RT-PCR,
      immunoblot and immunohistochemistry. Functional analysis of one of the highly
      expressed proteins, S100 calcium binding protein A2 (S100A2), was performed using
      RNA interference. As a consequence, attenuated S100A2 expression enhanced the
      ability of HEp-2 cell lines to migrate and invade in vitro. Our investigation
      complements the current understanding of laryngeal cancer progression.
      Furthermore, this study supports the concept that enhanced expression of S100A2
      may be a promising strategy in developing novel cancer therapeutic drugs.

PMID- 25874883
TI  - The effect of low-frequency road noise on driver sleepiness and performance.
AB  - It is a well-known fact today that driver sleepiness is a contributory factor in
      crashes. Factors considered as sleepiness contributor are mostly related to time
      of the day, hours being awake and hours slept. Factors contributing to active and
      passive fatigue are mostly focusing on the level of cognitive load. Less is known
      what role external factors, e.g. type of road, sound/noise, vibrations etc., have
      on the ability to stay awake both under conditions of sleepiness and under active
      or passive fatigue. The aim of this moving base driving simulator study with 19
      drivers participating in a random order day and night time, was to evaluate the
      effect of low-frequency road noise on driver sleepiness and performance,
      including both long-term and short-term effects. The results support to some
      extent the hypothesis that road-induced interior vehicle sound affects driving
      performance and driver sleepiness. Increased low-frequency noise helps to reduce
      speed during both day- and night time driving, but also contributes to increase
      the number of lane crossings during night time. 

PMID- 25874881
TI  - Psychological interventions for parents of children and adolescents with chronic
      illness.
AB  - BACKGROUND: Psychological therapies have been developed for parents of children
      and adolescents with a chronic illness. Such therapies include interventions
      directed at the parent only or at parent and child/adolescent, and are designed
      to improve parent, child, and family outcomes. This is an updated version of the
      original Cochrane review published in Issue 8, 2012, (Psychological interventions
      for parents of children and adolescents with chronic illness). OBJECTIVES: To
      evaluate the efficacy of psychological therapies that include parents of children
      and adolescents with chronic illnesses including painful conditions, cancer,
      diabetes mellitus, asthma, traumatic brain injury (TBI), inflammatory bowel
      diseases (IBD), skin diseases, or gynaecological disorders. We also aimed to
      evaluate the adverse events related to implementation of psychological therapies
      for this population. Secondly, we aimed to evaluate the risk of bias of included
      studies and the quality of outcomes using the GRADE assessment. SEARCH METHODS:
      We searched the Cochrane Central Register of Controlled Trials (CENTRAL),
      MEDLINE, EMBASE and PsycINFO for randomised controlled trials (RCTs) of
      psychological interventions that included parents of children and adolescents
      with a chronic illness. Databases were searched to July 2014. SELECTION CRITERIA:
      Included studies were RCTs of psychological interventions that delivered
      treatment to parents of children and adolescents with a chronic illness compared
      to an active control, waiting list, or treatment as usual control group. DATA
      COLLECTION AND ANALYSIS: Study characteristics and outcomes were extracted from
      included studies. We analysed data using two categories. First, we analysed data
      by each individual medical condition collapsing across all treatment classes at
      two time points. Second, we analysed data by each individual treatment class;
      cognitive behavioural therapy (CBT), family therapy (FT), problem solving therapy
      (PST) and multisystemic therapy (MST) collapsing across all medical conditions.
      For both sets of analyses we looked immediately post-treatment and at the first
      available follow-up. We assessed treatment effectiveness for two primary
      outcomes: parent behaviour and parent mental health. Five secondary outcomes were
      extracted; child behaviour/disability, child mental health, child symptoms,
      family functioning, and adverse events. Risk of bias and quality of evidence were
      assessed. MAIN RESULTS: Thirteen studies were added in this update, giving a
      total of 47 RCTs. The total number of participants included in the data analyses
      was 2985, 804 of whom were added to the analyses in the update. The mean age of
      the children was 14.6 years. Of the 47 RCTs, the studies focused on the following
      paediatric conditions: n = 14 painful conditions, n = 13 diabetes, n =10 cancer,
      n = 5 asthma, n = 4 TBI, and n = 1 atopic eczema. We did not identify any studies
      treating parents of children with gynaecological disorders or IBD. Risk of bias
      assessments of included studies were predominantly unclear. Evidence quality,
      assessed using the GRADE criteria, was judged to be of low or very low
      quality.Analyses of separate medical conditions, across all treatment types,
      revealed two beneficial effects of psychological therapies for our primary
      outcomes. First, psychological therapies led to improved adaptive parenting
      behaviour in parents of children with cancer post-treatment (standardised mean
      difference (SMD) -0.20, 95% confidence interval (CI) -0.36 to -0.04, Z = 2.44, p
      = 0.01). In addition, therapies also improved parent mental health at follow-up
      in this group (SMD = -0.18, 95% CI -0.32 to -0.04, Z = 2.58, p = 0.01). We did
      not find any effect of therapies for parent behaviour for parents of children
      with a painful condition post-treatment or at follow-up, or for parent mental
      health for parents of children with cancer, diabetes, asthma, or TBI post
      treatment. For all other primary outcomes, no analysis could be conducted due to
      lack of data.Across all medical conditions, three effects were found for the
      primary outcomes of psychological therapies. PST had a beneficial effect on
      parent adaptive behaviour (SMD = -0.25, 95% CI -0.39 to -0.11, Z = 3.59, p <
      0.01) and parent mental health (SMD= -0.24, 95% CI -0.42 to -0.05, Z = 2.50, p =
      0.01) immediately post-treatment and this effect was maintained at follow-up for
      parent mental health (SMD= -0.19, 95% CI -0.34 to -0.04, Z = 2.55, p = 0.01). The
      remaining analysis for PST on parent behaviour found no effect. No effects were
      found for CBT post-treatment or at follow-up for either parent outcome. For FT,
      only one analysis could be run on parent mental health and no effect was found.
      Due to lack of data, the remaining analyses of primary outcomes could not be run.
      For MST, no parent outcomes could be analysed due to lack of data.Secondary
      outcome analyses are presented in the Results section. Five studies reported that
      there were no adverse events during the trial. The remaining 42 studies did not
      report adverse events. AUTHORS' CONCLUSIONS: This update includes 13 additional
      studies, although our conclusions have not changed from the original version.
      There is little evidence for the efficacy of psychological therapies that include
      parents on most outcome domains of functioning, for a large number of common
      chronic illnesses in children. However, psychological therapies are efficacious
      for some outcomes. CBT that includes parents is beneficial for reducing
      children's primary symptoms, and PST that includes parents improved parent
      adaptive behaviour and parent mental health. There is evidence that the
      beneficial effects can be maintained at follow-up for diabetes-related symptoms
      in children, and for the mental health of parents of children with cancer and
      parents who received PST.

PMID- 25874885
TI  - Parameter identification in a tuberculosis model for Cameroon.
AB  - A deterministic model of tuberculosis in Cameroon is designed and analyzed with
      respect to its transmission dynamics. The model includes lack of access to
      treatment and weak diagnosis capacity as well as both frequency- and density
      dependent transmissions. It is shown that the model is mathematically well-posed
      and epidemiologically reasonable. Solutions are non-negative and bounded whenever
      the initial values are non-negative. A sensitivity analysis of model parameters
      is performed and the most sensitive ones are identified by means of a state-of
      the-art Gauss-Newton method. In particular, parameters representing the
      proportion of individuals having access to medical facilities are seen to have a
      large impact on the dynamics of the disease. The model predicts that a gradual
      increase of these parameters could significantly reduce the disease burden on the
      population within the next 15 years. 

PMID- 25874886
TI  - Why do women deliver at home? Multilevel modeling of Ethiopian National
      Demographic and Health Survey data.
AB  - BACKGROUND: Despite of the existing intensive efforts to improve maternal health
      in Ethiopia, the proportion of birth delivered at home remains high and is still
      the top priority among the national health threats. OBJECTIVE: The study aimed to
      examine effects of individual women and community-level factors of women's
      decision on place of delivery in Ethiopia. METHODS: Data were obtained from the
      nationally representative 2011 Ethiopian Demographic and Health Survey (EDHS)
      which used a two-stage cluster sampling design with rural-urban and regions as
      strata. The EDHS collected data from a big sample size but our study focused on a
      sample of 7,908 women whose most recent birth was within five years preceding
      2011 and 576 communities in which the women were living in. The data were
      analyzed using a two-level mixed-effects logistic regression to determine fixed
      effects of individual- and community-level factors and random-intercept of
      between-cluster characteristics. RESULTS: In the current study, 6980 out of 7908
      deliveries (88.3%) took place at home. Lower educational levels (OR=2.74,
      95%CI:1.84,4.70; p<0.0001), making no or only a limited number of ANC visits
      (OR=3.72,95%CI:2.85, 4.83; p<0.0001), non-exposure to media (OR=1.51, 95%CI 1.13,
      2.01; p=0.004), higher parity (OR=2.68, 95%CI:1.96,3.68; p<0.0001), and perceived
      distance problem to reach health facilities (OR=1.29, 95%CI:1.03,1.62; p=0.022)
      were positively associated with home delivery. About 75% of the total variance in
      the odds of giving birth at home was accounted for the between-community
      differences of characteristics (ICC=0.75, p<0.0001). With regard to community
      level characteristics, rural communities (OR=4.67, 95%CI:3.06,7.11; p<0.0001),
      pastoralist communities (OR=4.53, 95%CI:2.81,7.28; p<0.0001), communities with
      higher poverty levels (OR=1.49 95%CI:1.08,2.22; p=0.048), with lower levels of
      ANC utilization (OR=2.01, 95%CI:1.42,2.85; p<0.0001) and problem of distance to a
      health facility (OR=1.29, 95%CI:1.03,1.62; p=0.004) had a positive influence on
      women to give birth at home. CONCLUSIONS: Not only individual characteristics of
      women, but also community-level factors determine women's decision to deliver at
      home.

PMID- 25874884
TI  - A paradigm shift: Cancer therapy with peptide-based B-cell epitopes and peptide
      immunotherapeutics targeting multiple solid tumor types: Emerging concepts and
      validation of combination immunotherapy.
AB  - There is a recognizable and urgent need to speed the development and application
      of novel, more efficacious anti-cancer vaccine therapies that inhibit tumor
      progression and prevent acquisition of tumor resistance. We have created and
      established a portfolio of validated peptide epitopes against multiple receptor
      tyrosine kinases and we have identified the most biologically effective
      combinations of EGFR (HER-1), HER-2, HER-3, VEGF and IGF-1R peptide
      vaccines/mimics to selectively inhibit multiple receptors and signaling pathways.
      The strategy is based on the use of chimeric conformational B-cell epitope
      peptides incorporating "promiscuous" T-cell epitopes that afford the possibility
      of generating an enduring immune response, eliciting protein-reactive high
      affinity anti-peptide antibodies as potential vaccines and peptide mimics that
      act as antagonists to receptor signaling that drive cancer metastasis. In this
      review we will summarize our ongoing studies based on the development of
      combinatorial immunotherapeutic strategies that act synergistically to enhance
      immune-mediated tumor killing aimed at addressing mechanisms of tumor resistance
      for several tumor types. 

PMID- 25874888
TI  - Designed Formation of Co3O4/NiCo2O4 Double-Shelled Nanocages with Enhanced
      Pseudocapacitive and Electrocatalytic Properties.
AB  - Hollow structures with high complexity in shell architecture and composition have
      attracted tremendous interest because of their great importance for both
      fundamental studies and practical applications. Herein we report the designed
      synthesis of novel box-in-box nanocages (NCs) with different shell compositions,
      namely, Co3O4/NiCo2O4 double-shelled nanocages (DSNCs). Uniform zeolitic
      imidazolate framework-67/Ni-Co layered double hydroxides yolk-shelled structures
      are first synthesized and then transformed into Co3O4/NiCo2O4 DSNCs by thermal
      annealing in air. Importantly, this strategy can be easily extended to prepare
      other complex DSNCs. When evaluated as electrodes for pseudocapacitors, the
      Co3O4/NiCo2O4 DSNCs show a high specific capacitance of 972 F g(-1) at a current
      density of 5 A g(-1) and excellent stability with 92.5% capacitance retention
      after 12 000 cycles, superior to that of Co3O4 NCs with simple configuration and
      Co3O4/Co3O4 DSNCs. Besides, the Co3O4/NiCo2O4 DSNCs also exhibit much better
      electrocatalytic activity for the oxygen evolution reaction than Co3O4 NCs. The
      greatly improved electrochemical performance of Co3O4/NiCo2O4 DSNCs demonstrates
      the importance of rational design and synthesis of hollow structures with higher
      complexity. 

PMID- 25874887
TI  - Impact of body mass index on in-hospital complications in patients undergoing
      percutaneous coronary intervention in a Japanese real-world multicenter registry.
AB  - BACKGROUND: Obesity is associated with advanced cardiovascular disease. However,
      some studies have reported the "obesity paradox" after percutaneous coronary
      intervention (PCI). The relationship between body mass index (BMI) and clinical
      outcomes after PCI has not been thoroughly investigated, especially in Asian
      populations. METHODS: We studied 10,142 patients who underwent PCI at 15 Japanese
      hospitals participating in the JCD-KICS registry from September 2008 to April
      2013. Patients were divided into four groups according to BMI: underweight, BMI
      <18.5 (n=462); normal, BMI >= 18.5 and <25.0 (n=5,945); overweight, BMI >= 25.0
      and <30.0 (n=3,100); and obese, BMI >= 30.0 (n=635). RESULTS: Patients with a
      high BMI were significantly younger (p<0.001) and had a higher incidence of
      coronary risk factors such as hypertension (p<0.001), hyperlipidemia (p<0.001),
      diabetes mellitus (p<0.001), and current smoking (p<0.001), than those with a low
      BMI. Importantly, patients in the underweight group had the worst in-hospital
      outcomes, including overall complications (underweight, normal, overweight, and
      obese groups: 20.4%, 11.5%, 8.4%, and 10.2%, p<0.001), in-hospital mortality
      (5.8%, 2.1%, 1.2%, and 2.7%, p<0.001), cardiogenic shock (3.5%, 2.0%, 1.5%, and
      1.6%, p=0.018), bleeding complications (10.0%, 4.5%, 2.6%, and 2.8%, p<0.001),
      and receiving blood transfusion (7.6%, 2.7%, 1.6%, and 1.7%, p<0.001). BMI was
      inversely associated with bleeding complications after adjustment by multivariate
      logistic regression analysis (odds ratio, 0.95; 95% confidence interval, 0.92
      0.98; p=0.002). In subgroup multivariate analysis of patients without cardiogenic
      shock, BMI was inversely associated with overall complications (OR, 0.98; 95% CI,
      0.95-0.99; p=0.033) and bleeding complications (OR, 0.95; 95% CI, 0.91-0.98;
      p=0.006). Furthermore, there was a trend that BMI was moderately associated with
      in-hospital mortality (OR, 0.94; 95% CI, 0.88-1.01; p=0.091). CONCLUSIONS: Lean
      patients, rather than obese patients are at greater risk for in-hospital
      complications during and after PCI, particularly for bleeding complications.

PMID- 25874889
TI  - Elder abuse in Chinese populations: a global review.
AB  - This review focuses on the epidemiology of elder abuse in the global Chinese
      population with respect to its prevalence, risk factors, and consequences, as
      well as the perceptions of elder abuse. Evidence revealed that elder abuse and
      its subtypes are common among the global Chinese population with prevalence
      ranging from 0.2% to 64%. Younger age, lower income levels, depression, cognitive
      impairment, and lack of social support were consistently associated with self
      reported elder abuse. Caregiver burden was a constant risk factor for the
      proclivity to elder abuse by caregivers. The adverse health outcomes of elder
      abuse included suicidal ideation and psychological stress. Some primary research
      gaps exist: such as, lack of consistency in measurements and recall periods,
      insufficient studies on the causal relationships between potential risk factors
      and elder abuse, consequences of elder abuse, and possible interventions. In
      order to reduce the risk of elder abuse in the global Chinese population,
      collaboration is encouraged among researchers, health care professionals, social
      service providers, and policy makers. 

PMID- 25874891
TI  - Comparative Cost of Stockpiling Various Types of Respiratory Protective Devices
      to Protect the Health Care Workforce During an Influenza Pandemic.
AB  - Specific guidance on the size and composition of respiratory protective device
      (RPD) stockpiles for use during a pandemic is lacking. We explore the economic
      aspects of stockpiling various types and combinations of RPDs by adapting a
      pandemic model that estimates the impact of a severe pandemic on a defined
      population, the number of potential interactions between patients and health care
      personnel, and the potential number of health care personnel needed to fulfill
      those needs. Our model calculates the number of the different types of RPDs that
      should be stockpiled and the consequent cost of purchase and storage, prorating
      this cost over the shelf life of the inventory. Compared with disposable N95 or
      powered air-purifying respirators, we show that stockpiling reusable elastomeric
      half-face respirators is the least costly approach. Disposable N95 respirators
      take up significantly more storage space, which increases relative costs. Reusing
      or extending the usable period of disposable devices may diminish some of these
      costs. We conclude that stockpiling a combination of disposable N95 and reusable
      half-face RPDs is the best approach to preparedness for most health care
      organizations. We recommend against stockpiling powered air-purifying respirators
      as they are much more costly than alternative approaches.

PMID- 25874890
TI  - Identification of critical residues of linear B cell epitope on Goodpasture
      autoantigen.
AB  - BACKGROUND: The autoantigen of anti-glomerular basement membrane (GBM) disease
      has been identified as the non-collagenous domain 1 of alpha3 chain of type IV
      collagen, alpha3(IV)NC1. Our previous study revealed a peptide on alpha3(IV)NC1
      as a major linear epitope for B cells and potentially nephrogenic, designated as
      P14 (alpha3129-150). This peptide has also been proven to be the epitope of auto
      reactive T cells in anti-GBM patients. This study was aimed to further
      characterize the critical motif of P14. METHODS: 16 patients with anti-GBM
      disease and positive anti-P14 antibodies were enrolled. A set of truncated and
      alanine substituted peptides derived from P14 were synthesized. Circulating
      antibodies against the peptides were detected by enzyme linked immunosorbent
      assay (ELISA). RESULTS: We found that all sera with anti-P14 antibodies reacted
      with the 13-mer sequence in the C-terminus of P14 (P14c) exclusively. The level
      of antibodies against P14 was highly correlated with the level of antibodies
      against P14c (r=0.970, P<0.001). P14c was the core immunogenic region and the
      amino acid sequence (ISLWKGFSFIMFT) was highly hydrophobic. Each amino acid
      residue in P14c was sequentially replaced by alanine. Three residues of
      glycine142, phenylalanine143, and phenylalanine145 were identified crucial for
      antibody binding based on the remarkable decline (P<0.001) of antibody reaction
      after each residue replacement. CONCLUSIONS: We defined GFxF (alpha3142, 143,145)
      as the critical motif of P14. It may provide some clues for understanding the
      etiology of anti-GBM disease.

PMID- 25874892
TI  - Correction to Effective dose of dental CBCT--a meta analysis of published data
      and additional data for nine CBCT units.

PMID- 25874893
TI  - Identification of non-coding RNAs associated with telomeres using a combination
      of enChIP and RNA sequencing.
AB  - Accumulating evidence suggests that RNAs interacting with genomic regions play
      important roles in the regulation of genome functions, including X chromosome
      inactivation and gene expression. However, to our knowledge, no non-biased
      methods of identifying RNAs that interact with a specific genomic region have
      been reported. Here, we used enChIP-RNA-Seq, a combination of engineered DNA
      binding molecule-mediated chromatin immunoprecipitation (enChIP) and RNA
      sequencing (RNA-Seq), to perform a non-biased search for RNAs interacting with
      telomeres. In enChIP-RNA-Seq, the target genomic regions are captured using an
      engineered DNA-binding molecule such as a transcription activator-like protein.
      Subsequently, RNAs that interact with the target genomic regions are purified and
      sequenced. The RNAs detected by enChIP-RNA-Seq contained known telomere-binding
      RNAs, including the telomerase RNA component (Terc), the RNA component of
      mitochondrial RNA processing endoribonuclease (Rmrp), and Cajal body-specific
      RNAs. In addition, a number of novel telomere-binding non-coding RNAs were also
      identified. Binding of two candidate non-coding RNAs to telomeres was confirmed
      by immunofluorescence microscopy and RNA fluorescence in situ hybridization (RNA
      FISH) analyses. The novel telomere-binding non-coding RNAs identified here may
      play important roles in telomere functions. To our knowledge, this study is the
      first non-biased identification of RNAs associated with specific genomic regions.
      The results presented here suggest that enChIP-RNA-Seq analyses are useful for
      the identification of RNAs interacting with specific genomic regions, and may
      help to contribute to current understanding of the regulation of genome
      functions. 

PMID- 25874895
TI  - A new method to scan genomes for introgression in a secondary contact model.
AB  - Secondary contact between divergent populations or incipient species may result
      in the exchange and introgression of genomic material. We develop a simple DNA
      sequence measure, called Gmin, which is designed to identify genomic regions
      experiencing introgression in a secondary contact model. Gmin is defined as the
      ratio of the minimum between-population number of nucleotide differences in a
      genomic window to the average number of between-population differences. Although
      it is conceptually simple, one advantage of Gmin is that it is computationally
      inexpensive relative to model-based methods for detecting gene flow and it scales
      easily to the level of whole-genome analysis. We compare the sensitivity and
      specificity of Gmin to those of the widely used index of population
      differentiation, FST, and suggest a simple statistical test for identifying
      genomic outliers. Extensive computer simulations demonstrate that Gmin has both
      greater sensitivity and specificity for detecting recent introgression than does
      FST. Furthermore, we find that the sensitivity of Gmin is robust with respect to
      both the population mutation and recombination rates. Finally, a scan of Gmin
      across the X chromosome of Drosophila melanogaster identifies candidate regions
      of introgression between sub-Saharan African and cosmopolitan populations that
      were previously missed by other methods. These results show that Gmin is a
      biologically straightforward, yet powerful, alternative to FST, as well as to
      more computationally intensive model-based methods for detecting gene flow.

PMID- 25874894
TI  - Plasmodium vivax populations are more genetically diverse and less structured
      than sympatric Plasmodium falciparum populations.
AB  - INTRODUCTION: The human malaria parasite, Plasmodium vivax, is proving more
      difficult to control and eliminate than Plasmodium falciparum in areas of co
      transmission. Comparisons of the genetic structure of sympatric parasite
      populations may provide insight into the mechanisms underlying the resilience of
      P. vivax and can help guide malaria control programs. METHODOLOGY/PRINCIPLE
      FINDINGS: P. vivax isolates representing the parasite populations of four areas
      on the north coast of Papua New Guinea (PNG) were genotyped using microsatellite
      markers and compared with previously published microsatellite data from sympatric
      P. falciparum isolates. The genetic diversity of P. vivax (He = 0.83-0.85) was
      higher than that of P. falciparum (He = 0.64-0.77) in all four populations.
      Moderate levels of genetic differentiation were found between P. falciparum
      populations, even over relatively short distances (less than 50 km), with 21-28%
      private alleles and clear geospatial genetic clustering. Conversely, very low
      population differentiation was found between P. vivax catchments, with less than
      5% private alleles and no genetic clustering observed. In addition, the effective
      population size of P. vivax (30353; 13043-69142) was larger than that of P.
      falciparum (18871; 8109-42986). CONCLUSIONS/SIGNIFICANCE: Despite comparably high
      prevalence, P. vivax had higher diversity and a panmictic population structure
      compared to sympatric P. falciparum populations, which were fragmented into
      subpopulations. The results suggest that in comparison to P. falciparum, P. vivax
      has had a long-term large effective population size, consistent with more intense
      and stable transmission, and limited impact of past control and elimination
      efforts. This underlines suggestions that more intensive and sustained
      interventions will be needed to control and eventually eliminate P. vivax. This
      research clearly demonstrates how population genetic analyses can reveal deeper
      insight into transmission patterns than traditional surveillance methods.

PMID- 25874896
TI  - The knowledge, attitudes and beliefs of carers (parents, guardians, healthcare
      practitioners, creche workers) around fever and febrile illness in children aged
      5 years and under: protocol for a qualitative systematic review.
AB  - BACKGROUND: Many parents consider fever a disease in itself and feel disempowered
      when their child is ill. Numerous guidelines have been produced; however, their
      target audience remains healthcare professionals and not carers of children in
      general. A reliable source of information will decrease worry in parents and
      carers when managing a febrile child. METHODS/DESIGN: A systematic search will be
      conducted in nine electronic databases. Articles published in English, or with an
      abstract published in English, will be eligible for inclusion in the review.
      Unpublished literature, grey literature and consultation with experts in the area
      will be used to supplement database searching. Titles and abstracts of studies
      will be screened for inclusion in the study by two independent reviewers against
      pre-determined inclusion and exclusion criteria. A data extraction form will be
      designed and data will be extracted to provide detail of the included studies by
      a further two reviewers. Quality assessment of studies will be conducted by two
      additional independent reviewers and results will be used to moderate included
      studies. All disagreements will be resolved through discussion until consensus is
      reached. Thematic synthesis will be used to analyse results. DISCUSSION: Correct
      management of fever in children is not well understood in the general population.
      Although carers can identify fever and febrile illness in children, determination
      of the severity of fever proves challenging. Research is needed to cohere
      existing evidence and identify knowledge gaps. It is envisaged that results of
      this review will contribute to the development of trustworthy, accessible
      guidelines for parents and carers of children with fever or febrile illness.
      SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42014009812.

PMID- 25874898
TI  - Feasibility and Acceptability of Google Glass for Emergency Department
      Dermatology Consultations.

PMID- 25874899
TI  - Investigation of different approaches to incorporating internal standard in DBS
      quantitative bioanalytical workflows and their effect on nullifying hematocrit
      based assay bias.
AB  - Hematocrit (HCT)-based assay bias (composed of area and recovery bias) is an
      important contributing factor to the barriers that currently hinder the
      development and acceptance of dried blood spots (DBS) as a widely used
      quantitative bioanalytical sampling technique for regulatory studies. This
      article describes the evaluation of a practical internal standard spray addition
      technique, used prior to LC-MS/MS analysis, which is demonstrated to nullify the
      effect of recovery bias. To our knowledge, this is the first time a potential
      solution to HCT-based recovery bias has been investigated in detail and reported
      in the literature. This new technique is coupled with accurate volume DBS
      sampling, whole-spot extraction, and automated direct elution techniques to
      demonstrate a workflow that both nullifies HCT-based assay bias and the
      additional manual extraction burden associated with DBS analysis. 

PMID- 25874901
TI  - Smart nanoparticles as targeting platforms for HIV infections.
AB  - While Human Immunodeficiency Virus (HIV) infections are reducing in incidence
      with the advent of Highly Active Anti-retroviral Therapy (HAART), there remain a
      number of challenges including the existence of reservoirs, drug resistance and
      anatomical barriers to antiretroviral therapy. To overcome these, smart
      nanoparticles with stimuli responsive release are proposed for delivery of anti
      retroviral agents. The paper highlights the strategic similarities between the
      design of smart antiretroviral nanocarriers and those optimized for cancer
      chemotherapy. This includes the development of nanoparticles capable of passive
      and active targeting as well as those that are responsive to various internal and
      external triggers. For antiretroviral therapy, the relevant triggers for stimuli
      responsive release of drugs include semen, enzymes, endosomal escape, temperature
      and magnetic field. Deriving from the experience of cancer chemotherapy,
      additional potential triggers are light and ultrasound which remain hitherto
      unexplored in HIV therapy. In addition, the roles of nanomicrobicides (nanogels)
      and virus mimetic nanoparticles are discussed from the point of view of
      prevention of HIV transmission. The challenges associated with translation of
      smart nanoparticles for HIV infections to realize the Millennium Development Goal
      of combating HIV infections are discussed. 

PMID- 25874902
TI  - Quantitative mass spectrometry measurements reveal stoichiometry of principal
      postsynaptic density proteins.
AB  - Quantitative studies are presented of postsynaptic density (PSD) fractions from
      rat cerebral cortex with the ultimate goal of defining the average copy numbers
      of proteins in the PSD complex. Highly specific and selective isotope dilution
      mass spectrometry assays were developed using isotopically labeled polypeptide
      concatemer internal standards. Interpretation of PSD protein stoichiometry was
      achieved as a molar ratio with respect to PSD-95 (SAP-90, DLG4), and
      subsequently, copy numbers were estimated using a consensus literature value for
      PSD-95. Average copy numbers for several proteins at the PSD were estimated for
      the first time, including those for AIDA-1, BRAGs, and densin. Major findings
      include evidence for the high copy number of AIDA-1 in the PSD (144 +/- 30)
      equivalent to that of the total GKAP family of proteins (150 +/- 27)-suggesting
      that AIDA-1 is an element of the PSD scaffold. The average copy numbers for NMDA
      receptor sub-units were estimated to be 66 +/- 18, 27 +/- 9, and 45 +/- 15,
      respectively, for GluN1, GluN2A, and GluN2B, yielding a total of 34 +/- 10 NMDA
      channels. Estimated average copy numbers for AMPA channels and their auxiliary
      sub-units TARPs were 68 +/- 36 and 144 +/- 38, respectively, with a stoichiometry
      of ~1:2, supporting the assertion that most AMPA receptors anchor to the PSD via
      TARP sub-units. This robust, quantitative analysis of PSD proteins improves upon
      and extends the list of major PSD components with assigned average copy numbers
      in the ongoing effort to unravel the complex molecular architecture of the PSD. 

PMID- 25874903
TI  - A method for long-term live imaging of tissue macrophages in adipose tissue
      explants.
AB  - Obesity is frequently associated with a chronic low-grade inflammation within
      adipose tissue (AT). Although classical signs of inflammation are missing in AT
      inflammation, there is a significant increase in macrophages and, to a lesser
      extent, other immune cells, such as T cells, B cells, mast cells, and
      neutrophils. The spatial and temporal activation of these cells as well as their
      accumulation in the AT seem to be tightly linked to so-called crown-like
      structures (CLS). CLS are accumulations of adipose tissue macrophages (ATMs)
      around dead adipocytes and are thought to reflect a scavenger response. At
      present, data on the life cycle of CLS are missing. To better understand the
      cellular events underlying AT inflammation, we developed an approach that allows
      long-term imaging of ATMs, adipocytes, and CLS within live AT explants. We tested
      three putative reporter mouse lines for myeloid cells in regard to their
      suitability for live imaging. Thereby, we identified ATMs from CSF1R-eGFP mice to
      exhibit the most robust expression of eGFP. AT explants from these mice allowed
      stable live imaging for more than 7 days without significant phototoxicity. Long
      term imaging thus revealed the accumulation of ATMs around dying adipocytes,
      migration of ATMs within AT, and also the degradation of the lipid remnants of
      perishing adipocytes. The observed behavior of ATMs in the context of AT
      inflammation is in line with previous studies but for the first time provides
      data on the specific behavior of individual ATMs and on the life cycle of CLS
      with unprecedented spatiotemporal resolution. 

PMID- 25874905
TI  - Janus gas: reversible redox transition of Sarin enables its selective detection
      by an ethanol modified nanoporous SnO2 chemiresistor.
AB  - A reversible janus gas redox transition was discovered in the trace Sarin sensing
      process using an ethanol-aged nanoporous SnO2 micro-chemiresistor, which was
      reliable to realize the identification of Sarin from other gases and even its
      simulant. This sensor also endows a rather low detection threshold of 6 ppb to
      Sarin. 

PMID- 25874904
TI  - Nutritional vitamin D supplementation and health-related outcomes in hemodialysis
      patients: a protocol for a systematic review and meta-analysis.
AB  - BACKGROUND: The prevalence of vitamin D deficiency in hemodialysis patients is
      high. While most hemodialysis patients are treated with activated vitamin D
      (1,25[OH]2D) to prevent renal osteodystrophy, clinical practices of the screening
      and treatment of 25(OH)2D deficiency are highly variable. It is unclear if
      nutritional vitamin D supplementation with D2 or D3 provides an additional
      clinical benefit beyond that provided by activated vitamin D treatment in this
      population. METHODS/DESIGN: We will conduct a systematic review of nutritional
      vitamin D (D2/D3) supplementation and health-related outcomes in hemodialysis
      patients according to Preferred Reporting Items for Systematic Reviews and Meta
      Analyses (PRISMA) guidelines. The primary objective is to assess the impact of
      nutritional vitamin D supplementation on clinical outcomes relevant in
      hemodialysis patients, such as mortality, cardiovascular events, infections, and
      fractures. Secondary outcomes will include anemia, hyperparathyroidism,
      medication use (erythrocyte-stimulating agents, activated vitamin D), and quality
      of life. We will search MEDLINE, Scopus, Web of Science, and ClinicalTrials.gov
      for randomized, controlled trials of nutritional vitamin D supplementation
      (ergocalciferol/D2 or cholecalciferol/D3) in chronic hemodialysis patients. The
      Cochrane Risk Assessment Tool will be used to assess the quality of eligible
      studies. We will perform meta-analyses using standard techniques for the outcomes
      listed above if pooling is deemed appropriate/sufficient. The results of this
      systematic review may highlight gaps in our knowledge of the relevance of
      nutritional vitamin D in end-stage renal disease, allowing for the informed
      design of clinical trials assessing the impact of nutritional vitamin D therapy
      in the hemodialysis population in the future. SYSTEMATIC REVIEW REGISTRATION:
      PROSPERO CRD42014013931.

PMID- 25874907
TI  - Normative Data for the Neurobehavioral Symptom Inventory.
AB  - The demographically diverse populations served by large health care systems
      (Veterans Affairs, Department of Defense, Medicare, Medicaid) are routinely
      screened with the Neurobehavioral Symptom Inventory (NSI). The extent to which a
      patient's report of symptoms either initially and/or across time is affected by
      demographic variables-gender, ethnicity, age, or education-has not been
      investigated despite widespread use of the NSI. In practice, the effectiveness of
      this tool might be improved with demographically based norms. A large data set of
      normal community-dwelling individuals was collected using the NSI. Emphasis was
      made to collect data from individuals of diverse ethnic backgrounds. It was
      hypothesized that ethnic/cultural backgrounds would have an impact on NSI scores.
      The results provide normative data for the NSI applicable to a wide variety of
      individuals of various ages and ethnic backgrounds. An analysis of variance
      indicated there was no significant difference in NSI responses based on
      ethnic/cultural background; however, age and gender were found to contribute
      significantly to the variance associated with symptom endorsement. The NSI
      appears to be a reliable measure of self-report postconcussive symptoms. Age is a
      variable associated with differential symptom endorsement on the NSI. Follow-up
      studies are needed to provide a measure of the sensitivity and specificity of
      this measure. 

PMID- 25874906
TI  - Glucose-coated superparamagnetic iron oxide nanoparticles prepared by metal
      vapour synthesis are electively internalized in a pancreatic adenocarcinoma cell
      line expressing GLUT1 transporter.
AB  - Iron oxide nanoparticles (IONP) can have a variety of biomedical applications due
      to their visualization properties through Magnetic Resonance Imaging (MRI) and
      heating with radio frequency or alternating magnetic fields. In the oncological
      field, coating IONP with organic compounds to provide specific features and to
      achieve the ability of binding specific molecular targets appears to be very
      promising. To take advantage of the high avidity of tumor cells for glucose, we
      report the development of very small glucose-coated IONP (glc-IONP) by employing
      an innovative technique, Metal Vapor Synthesis (MVS). Moreover, we tested the
      internalization of our gl-IONP on a tumor line, BxPC3, over-expressing GLUT 1
      transporter. Both glc-IONP and polyvinylpyrrolidone-IONP (PVP-IONP), as control,
      were prepared with MVS and were tested on BxPC3 at various concentrations. To
      evaluate the role of GLUT-1 transporter, we also investigated the effect of
      adding a polyclonal anti-GLUT1 antibody. After proper treatment, the iron value
      was assessed by atomic absorption spectrometer, reported in mcg/L and expressed
      in mg of protein. Our IONP prepared with MVS were very small and homogeneously
      distributed in a narrow range (1.75-3.75 nm) with an average size of 2.7 nm and
      were super-paramagnetic. Glc-IONP were internalized by BxPC3 cells in a larger
      amount than PVP-IONP. After 6h of treatment with 50 mcg/mL of IONPs, the content
      of Fe was 1.5 times higher in glc-IONP-treated cells compared with PVP-IONP
      treated cells. After 1h pre-treatment with anti-GLUT1, a reduction of 41%
      cellular accumulation of glc-IONP was observed. Conversely, the uptake of PVP
      IONPs was reduced only by 14% with antibody pretreatment. In conclusion, MVS
      allowed us to prepare small, homogeneous, super-paramagnetic glc-IONP, which are
      electively internalized by a tumor line over-expressing GLUT1. Our glc-IONP
      appear to have many requisites for in vivo use. 

PMID- 25874908
TI  - Race perception and gaze direction differently impair visual working memory for
      faces: An event-related potential study.
AB  - Humans are amazingly experts at processing and recognizing faces, however there
      are moderating factors of this ability. In the present study, we used the event
      related potential technique to investigate the influence of both race and gaze
      direction on visual working memory (i.e., VWM) face representations. In a change
      detection task, we orthogonally manipulated race (own-race vs. other-race faces)
      and eye-gaze direction (direct gaze vs. averted gaze). Participants were required
      to encode identities of these faces. We quantified the amount of information
      encoded in VWM by monitoring the amplitude of the sustained posterior
      contralateral negativity (SPCN) time-locked to the faces. Notably, race and eye
      gaze direction differently modulated SPCN amplitude such that other-race faces
      elicited reduced SPCN amplitudes compared with own-race faces only when
      displaying a direct gaze. On the other hand, faces displaying averted gaze,
      independently of their race, elicited increased SPCN amplitudes compared with
      faces displaying direct gaze. We interpret these findings as denoting that race
      and eye-gaze direction affect different face processing stages. 

PMID- 25874909
TI  - Colloidal Nanocrystal Frameworks.
AB  - Colloidal nanocrystal frameworks (CNFs) are a modular class of mesostructured
      porous materials, which are assembled from pre-formed nanocrystal building units
      using suitably designed block copolymer architecture-directing agents. The
      functional attributes of these frameworks are determined both by the
      physiochemical characteristics of the nanocrystal components as well as their
      ordered arrangements in space. It is noteworthy that their assembly schemes are
      readily amenable to more than one type of framework component, yielding a
      multivariate landscape to navigate mesoscale phenomena arising from the coupled
      interactions of different nanocrystals within the framework. Early reports
      indicate surprisingly efficient propagation of both matter and energy within and
      along the surfaces of these frameworks, although there remains much to be learned
      about the origins of their structural, electronic, and dynamic properties, and
      how they feed back across multiple length and time scales. 

PMID- 25874910
TI  - Cognitive and typing outcomes measured simultaneously with slow treadmill walking
      or sitting: implications for treadmill desks.
AB  - PURPOSE: This study compared cognitive (attention, learning, and memory) and
      typing outcomes during slow treadmill walking or sitting. Seventy-five healthy
      individuals were randomly assigned to a treadmill walking group (n=37; 23 female)
      or sitting group (n=38; 17 female). METHODS: The treadmill walking group
      completed a series of tests while walking at 1.5 mph. The sitting group performed
      the same tests while sitting at a standard desk. Tests performed by both groups
      included: the Rey Auditory Verbal Learning Test and a modified version of the
      Paced Auditory Serial Attention Test. In addition, typing performance was
      evaluated. RESULTS: Participants in the treadmill walking group performed worse
      on the Rey Auditory Verbal Learning Test for total learning than the sitting
      group; the main effect was significant (F(1,73)=4.75, p=0.03, etap2=0.06);
      however, short- and long-delay recall performance did not differ between groups
      (p>0.05). For the Paced Auditory Serial Attention Test, total number of correct
      responses was lower in the treadmill walking group relative to the sitting group;
      the main effect was significant (F(1,73)=4.97, p=0.03, etap2=0.06). The
      performance of both groups followed the same learning slope (Group x Trial
      interactions were not significant) for the Rey Auditory Verbal Learning Test and
      Paced Auditory Serial Attention Test. Individuals in the treadmill walking group
      performed significantly worse for all measures of typing (p<0.05). CONCLUSION:
      Walking on a treadmill desk may result in a modest difference in total learning
      and typing outcomes relative to sitting, but those declines may not outweigh the
      benefit of the physical activity gains from walking on a treadmill.

PMID- 25874912
TI  - Correction: regeneration of Solanum nigrum by somatic embryogenesis, involving
      frog egg-like body, a novel structure.

PMID- 25874911
TI  - Wild soybean roots depend on specific transcription factors and oxidation
      reduction related genesin response to alkaline stress.
AB  - Soil alkalinity is an important environmental problem limiting agricultural
      productivity. Wild soybean (Glycine soja) shows strong alkaline stress tolerance,
      so it is an ideal plant candidate for studying the molecular mechanisms of
      alkaline tolerance and identifying alkaline stress-responsive genes. However,
      limited information is available about G. soja responses to alkaline stress on a
      genomic scale. Therefore, in the present study, we used RNA sequencing to compare
      transcript profiles of G. soja root responses to sodium bicarbonate (NaHCO3) at
      six time points, and a total of 68,138,478 pairs of clean reads were obtained
      using the Illumina GAIIX. Expression patterns of 46,404 G. soja genes were
      profiled in all six samples based on RNA-seq data using Cufflinks software. Then,
      t12 transcription factors from MYB, WRKY, NAC, bZIP, C2H2, HB, and TIFY families
      and 12 oxidation reduction related genes were chosen and verified to be induced
      in response to alkaline stress by using quantitative real-time polymerase chain
      reaction (qRT-PCR). The GO functional annotation analysis showed that besides
      "transcriptional regulation" and "oxidation reduction," these genes were involved
      in a variety of processes, such as "binding" and "response to stress." This is
      the first comprehensive transcriptome profiling analysis of wild soybean root
      under alkaline stress by RNA sequencing. Our results highlight changes in the
      gene expression patterns and identify a set of genes induced by NaHCO3 stress.
      These findings provide a base for the global analyses of G. soja alkaline stress
      tolerance mechanisms.

PMID- 25874913
TI  - Atorvastatin prevents neuroinflammation in chronic constriction injury rats
      through nuclear NFkappaB downregulation in the dorsal root ganglion and spinal
      cord.
AB  - Atorvastatin, traditionally used to treat hyperlipidemia, belongs to a class of 3
      hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors. This study
      investigated the antineuroinflammatory and antihyperalgesic effects of
      atorvastatin in dorsal root ganglia (DRG) and spinal cord for chronic
      constriction injury (CCI) neuropathic pain in rats. Fifty-four Sprague-Dawley
      rats were divided into three groups including sham, CCI, and CCI+atorvastatin.
      Rats were orally administered atorvastatin (10 mg/kg/day) once daily for 2 weeks
      after surgery and sacrificed at days 3, 7, and 14. All animals were assessed for
      mechanical allodynia and thermal hyperalgesia in both hindpaws. Western blotting,
      immunofluorescence, and enzyme-linked immunosorbent assay (ELISA) were used to
      detect inflammatory proteins and proinflammatory cytokines at day 7 after
      surgery. Pain behaviors were significantly reduced in the CCI+atorvastatin group
      compared to the CCI group. Atorvastatin attenuated CCI-induced inflammatory
      mediators (pAkt/Akt, COX-2, iNOS, EP1, and EP4) and reduced proinflammatory
      cytokines TNF-alpha and IL-1beta levels in DRG and spinal cord. Atorvastatin also
      inhibited nuclear pNFkappaB activation. Double immunofluorescent staining further
      demonstrated that pNFkappaB proteins were decreased by atorvastatin in DRG
      satellite cells and spinal microglia. Atorvastatin may primarily inhibit the
      nuclear translocation of pNFkappaB to prevent CCI-induced peripheral neuropathic
      pain. Atorvastatin exhibits antineuroinflammatory and antinociceptive properties
      in the central and peripheral nerve systems. 

PMID- 25874914
TI  - Transient agranulocytosis associated with ziprasidone in a 45-year-old man on
      hemodialysis.

PMID- 25874915
TI  - Insomnia and somnolence associated with second-generation antidepressants during
      the treatment of major depression: a meta-analysis.
AB  - BACKGROUND: Sleep reduction or enhancement is frequently observed with second
      generation antidepressant treatments, and they can be beneficial or harmful
      depending on the symptom profile of each subject. Nevertheless, relatively little
      attention has been given so far to rank those effects across compounds. The aim
      of this meta-analysis is to provide quantitative data about short-term rates of
      insomnia and somnolence associated with 14 second-generation antidepressants
      during the treatment of major depression. METHODS: A literature search and a
      search of unpublished documents were performed. Eligible studies focusing on MD
      patients treated with second-generation antidepressants were entered in the
      analysis. Our primary outcome measures were insomnia and somnolence rates induced
      by antidepressants as compared with those associated with placebo. Sensitivity
      analyses were carried out as well. RESULTS: Ten second-generation antidepressants
      showed higher rates of insomnia than placebo. The highest incidence was found for
      bupropion and desvenlafaxine. Agomelatine was the only antidepressant with a
      lower likelihood of inducing insomnia than placebo. Eleven antidepressants were
      associated with higher rates of somnolence than placebo. Fluvoxamine and
      mirtazapine showed the highest frequency of somnolence. Bupropion induced
      somnolence to a lower extent than placebo. Sensitivity analyses showed a degree
      of variation of those findings. DISCUSSION: Antidepressants are associated with
      different insomnia and somnolence rates, mainly depending on their mechanisms of
      action. Despite some limitations, we underscore that the treatment-emergent
      insomnia and/or somnolence are frequent, and they could be used in clinical
      practice to face the specific needs of each patient.

PMID- 25874917
TI  - Parkinsonism related to varenicline in a patient during smoking cessation.

PMID- 25874916
TI  - Antidepressant effects of open label treatment with coenzyme Q10 in geriatric
      bipolar depression.

PMID- 25874918
TI  - Silymarin treatment of obsessive-compulsive spectrum disorders.

PMID- 25874919
TI  - Evidence for shortening the duration of clinical trials of antidepressants and a
      proposed paradigm for such studies.
AB  - The model for the clinical trial of putative antidepressants is older than 50
      years. Recent failures resulted in several drug companies, citing excessive costs
      of lengthy multiweek trials, abandoning new drug development. Collateral problems
      include patients being maintained on ineffective drugs for 6 to 8 weeks,
      increasing the pain associated with the disorder. This study proposes an
      alternative model for testing new drugs that both shortens the clinical trial and
      broadens its aims to include a profile of the new drug's specific clinical
      actions. This alternative model makes it possible to uncover the drug's
      application to treatment of other mental disorders. It is based on recent
      findings that onset of action and a large proportion of an effective drug's
      positive effects, contrary to early reports, occur within the first 2 weeks. It
      uses an index of the 2-week "early improvement" to predict a 6-week outcome.
      Measuring effects on the dimensions of the disorder determined that effective
      antidepressants act on mood and behavioral components and that the Hamilton and
      new "multivantaged" methods can provide a profile of specific drug actions
      distinguished from nonspecific placebo effects, at 2 weeks. This early
      improvement is predictive of positive outcome of 6-week trials. Because of the
      implications of successful 2-week trials for reducing costs, providing data on
      specific clinical drug actions, potentially stimulating new drug development, and
      reducing patient suffering from extended treatment with ineffective drugs, a
      large sample, prospective study designed in accord with this test trial is
      recommended. 

PMID- 25874920
TI  - Hyperoxia elevates adrenic acid peroxidation in marine fish and is associated
      with reproductive pheromone mediators.
AB  - The development of oxidative stress in the marine ecosystem is a concurring
      concern in fish reproductive behavior. Marine fish being rich in polyunsaturated
      fatty acids (PUFA) are precursors of prostaglandin pheromone mediators but also
      vulnerable to lipid peroxidation. It is yet to be determined if hypoxia or
      hyperoxia environment, a cumulative effect in the marine ecosystem affect
      pheromone mediators in fish, and to understand if this is associated with the
      generation of oxidized lipid products of PUFA. Novel oxidized lipid metabolites,
      isoprostanoids (15-F2t-isoprostane, 7(RS)-7-F2t-dihomo-isoprostane, 17(RS)-17-F2t
      dihomo-isoprostane, 8-F3t-isoprostane, 4(RS)-4-F4t-neuroprostane, 10-F4t
      neuroprostane), isofuranoids (isofurans, 10-epi-17(RS)-SC-Delta15-11-dihomo
      isofuran and neurofurans), hydroxyeicosatetraenoic acids and resolvins, PUFA
      (arachidonic, adrenic, eicosapentaenoic and docosahexaenoic acids) and
      prostaglandin pheromone mediators in fish muscle were determined in marine male
      and female fish muscles before and after interaction in a hypoxia or hyperoxia
      environment. Reproductive behaviors were also assessed. Our study showed oxidized
      lipid metabolites of arachidonic, eicosapentaenoic, and docosahexaenoic acids
      were not influenced by hypoxia and hyperoxia exposure in the fishes and no gender
      differences were found. However, adrenic acid and its oxidized products, 17(RS)
      17-F2t-dihomo-isoprostane and 10-epi-17(RS)-SC-Delta15-11-dihomo-isofuran showed
      strong correspondence with male fish pheromone mediators and reproductive
      behavior when under oxidative stress especially, hyperoxia. The occurrence of
      hypoxia and hyperoxia in the marine ecosystem may not be detrimental to marine
      fish and instead presents as being beneficial in reproductive behavior. 

PMID- 25874921
TI  - Molecular and chemical analysis of the lipopolysaccharide from Aeromonas
      hydrophila strain AH-1 (Serotype O11).
AB  - A group of virulent Aeromonas hydrophila, A. sobria, and A. veronii biovar sobria
      strains isolated from humans and fish have been described; these strains
      classified to serotype O11 are serologically related by their lipopolysaccharide
      (LPS) O-antigen (O-polysaccharide), and the presence of an S-layer consisting of
      multiple copies of a crystalline surface array protein with a molecular weight of
      52 kDa in the form of a crystalline surface array which lies peripheral to the
      cell wall. A. hydrophila strain AH-1 is one of them. We isolated the LPS from
      this strain and determined the structure of the O-polysaccharide, which was
      similar to that previously described for another strain of serotype O11. The
      genetics of the O11-antigen showed the genes (wbO11 cluster) in two sections
      separated by genes involved in biosynthesis and assembly of the S-layer. The O11
      antigen LPS is an example of an ABC-2-transporter-dependent pathway for O-antigen
      heteropolysaccharide (disaccharide) assembly. The genes involved in the
      biosynthesis of the LPS core (waaO11 cluster) were also identified in three
      different chromosome regions being nearly identical to the ones described for A.
      hydrophila AH-3 (serotype O34). The genetic data and preliminary chemical
      analysis indicated that the LPS core for strain AH-1 is identical to the one for
      strain AH-3. 

PMID- 25874922
TI  - Neuroprotective effects of the cultivated Chondrus crispus in a C. elegans model
      of Parkinson's disease.
AB  - Parkinson's disease (PD) is the second most common neurodegenerative disorder in
      the elderly people, currently with no cure. Its mechanisms are not well
      understood, thus studies targeting cause-directed therapy or prevention are
      needed. This study uses the transgenic Caenorhabditis elegans PD model. We
      demonstrated that dietary supplementation of the worms with an extract from the
      cultivated red seaweed Chondrus crispus decreased the accumulation of alpha
      synulein and protected the worms from the neuronal toxin-, 6-OHDA, induced
      dopaminergic neurodegeneration. These effects were associated with a corrected
      slowness of movement. We also showed that the enhancement of oxidative stress
      tolerance and an up-regulation of the stress response genes, sod-3 and skn-1, may
      have served as the molecular mechanism for the C. crispus-extract-mediated
      protection against PD pathology. Altogether, apart from its potential as a
      functional food, the tested red seaweed, C. crispus, might find promising
      pharmaceutical applications for the development of potential novel anti
      neurodegenerative drugs for humans. 

PMID- 25874923
TI  - Esters of the marine-derived triterpene sipholenol A reverse P-GP-mediated drug
      resistance.
AB  - Our previous studies showed that several sipholane triterpenes, sipholenol A,
      sipholenone E, sipholenol L and siphonellinol D, have potent reversal effect for
      multidrug resistance (MDR) in cancer cells that overexpressed P-glycoprotein (P
      gp/ABCB1). Through comparison of cytotoxicity towards sensitive and multi-drug
      resistant cell lines, we identified that the semisynthetic esters sipholenol A-4
      O-acetate and sipholenol A-4-O-isonicotinate potently reversed P-gp-mediated MDR
      but had no effect on MRP1/ABCC1 and BCRP/ABCG2-mediated MDR. The results from
      [3H]-paclitaxel accumulation and efflux studies suggested that these two
      triterpenoids were able to increase the intracellular accumulation of paclitaxel
      by inhibiting its active efflux. In addition, western blot analysis revealed that
      these two compounds did not alter the expression levels of P-gp when treated up
      to 72 h. These sipholenol derivatives also stimulated the ATPase activity of P-gp
      membranes, which suggested that they might be substrates of P-gp. Moreover, in
      silico molecular docking studies revealed the virtual binding modes of these two
      compounds into human homology model of P-gp. In conclusion, sipholenol A-4-O
      acetate and sipholenol A-4-O-isonicotinate efficiently inhibit the P-gp and may
      represent potential reversal agents for the treatment of multidrug resistant
      cancers. 

PMID- 25874924
TI  - Piscidin is highly active against carbapenem-resistant Acinetobacter baumannii
      and NDM-1-producing Klebsiella pneumonia in a systemic Septicaemia infection
      mouse model.
AB  - This study was designed to investigate the antimicrobial activity of two
      synthetic antimicrobial peptides from an aquatic organism, tilapia piscidin 3
      (TP3) and tilapia piscidin 4 (TP4), in vitro and in a murine sepsis model, as
      compared with ampicillin, tigecycline, and imipenem. Mice were infected with (NDM
      1)-producing K. pneumonia and multi-drug resistant Acinetobacter baumannii, and
      subsequently treated with TP3, TP4, or antibiotics for different periods of time
      (up to 168 h). Mouse survival and bacterial colony forming units (CFU) in various
      organs were measured after each treatment. Toxicity was determined based on
      observation of behavior and measurement of biochemical parameters. TP3 and TP4
      exhibited strong activity against K. pneumonia and A. baumannii in vitro.
      Administration of TP3 (150 MUg/mouse) or TP4 (50 MUg/mouse) 30 min after
      infection with K. pneumonia or A. baumannii significantly increased survival in
      mice. TP4 was more effective than tigecycline at reducing CFU counts in several
      organs. TP3 and TP4 were shown to be non-toxic, and did not affect mouse
      behavior. TP3 and TP4 are able at potentiate anti-Acinetobacter baumannii or anti
      Klebsiella pneumonia drug activity, reduce bacterial load, and prevent drug
      resistance, indicating their potential for use in combating multidrug-resistant
      bacteria. 

PMID- 25874925
TI  - Xyloketal B attenuates atherosclerotic plaque formation and endothelial
      dysfunction in apolipoprotein e deficient mice.
AB  - Our previous studies demonstrated that xyloketal B, a novel marine compound with
      a unique chemical structure, has strong antioxidant actions and can protect
      against endothelial injury in different cell types cultured in vitro and model
      organisms in vivo. The oxidative endothelial dysfunction and decrease in nitric
      oxide (NO) bioavailability are critical for the development of atherosclerotic
      lesion. We thus examined whether xyloketal B had an influence on the
      atherosclerotic plaque area in apolipoprotein E-deficient (apoE-/-) mice fed a
      high-fat diet and investigated the underlying mechanisms. We found in our present
      study that the administration of xyloketal B dose-dependently decreased the
      atherosclerotic plaque area both in the aortic sinus and throughout the aorta in
      apoE-/- mice fed a high-fat diet. In addition, xyloketal B markedly reduced the
      levels of vascular oxidative stress, as well as improving the impaired
      endothelium integrity and NO-dependent aortic vasorelaxation in atherosclerotic
      mice. Moreover, xyloketal B significantly changed the phosphorylation levels of
      endothelial nitric oxide synthase (eNOS) and Akt without altering the expression
      of total eNOS and Akt in cultured human umbilical vein endothelial cells
      (HUVECs). Here, it increased eNOS phosphorylation at the positive regulatory site
      of Ser-1177, while inhibiting phosphorylation at the negative regulatory site of
      Thr-495. Taken together, these findings indicate that xyloketal B has dramatic
      anti-atherosclerotic effects in vivo, which is partly due to its antioxidant
      features and/or improvement of endothelial function. 

PMID- 25874927
TI  - Design modification and optimisation of the perfusion system of a tri-axial
      bioreactor for tissue engineering.
AB  - A systematic design of experiments (DOE) approach was used to optimize the
      perfusion process of a tri-axial bioreactor designed for translational tissue
      engineering exploiting mechanical stimuli and mechanotransduction. Four
      controllable design parameters affecting the perfusion process were identified in
      a cause-effect diagram as potential improvement opportunities. A screening
      process was used to separate out the factors that have the largest impact from
      the insignificant ones. DOE was employed to find the settings of the platen
      design, return tubing configuration and the elevation difference that minimise
      the load on the pump and variation in the perfusion process and improve the
      controllability of the perfusion pressures within the prescribed limits. DOE was
      very effective for gaining increased knowledge of the perfusion process and
      optimizing the process for improved functionality. It is hypothesized that the
      optimized perfusion system will result in improved biological performance and
      consistency. 

PMID- 25874926
TI  - Fucoidan and cancer: a multifunctional molecule with anti-tumor potential.
AB  - There is a wide variety of cancer types yet, all share some common cellular and
      molecular behaviors. Most of the chemotherapeutic agents used in cancer treatment
      are designed to target common deregulated mechanisms within cancer cells. Many
      healthy tissues are also affected by the cytotoxic effects of these chemical
      agents. Fucoidan, a natural component of brown seaweed, has anti-cancer activity
      against various cancer types by targeting key apoptotic molecules. It also has
      beneficial effects as it can protect against toxicity associated with
      chemotherapeutic agents and radiation. Thus the synergistic effect of fucoidan
      with current anti-cancer agents is of considerable interest. This review
      discusses the mechanisms by which fucoidan retards tumor development, eradicates
      tumor cells and synergizes with anti-cancer chemotherapeutic agents. Challenges
      to the development of fucoidan as an anti-cancer agent will also be discussed. 

PMID- 25874929
TI  - A closed-loop compressive-sensing-based neural recording system.
AB  - OBJECTIVE: This paper describes a low power closed-loop compressive sensing (CS)
      based neural recording system. This system provides an efficient method to reduce
      data transmission bandwidth for implantable neural recording devices. By doing
      so, this technique reduces a majority of system power consumption which is
      dissipated at data readout interface. The design of the system is scalable and is
      a viable option for large scale integration of electrodes or recording sites onto
      a single device. APPROACH: The entire system consists of an application-specific
      integrated circuit (ASIC) with 4 recording readout channels with CS circuits, a
      real time off-chip CS recovery block and a recovery quality evaluation block that
      provides a closed feedback to adaptively adjust compression rate. Since CS
      performance is strongly signal dependent, the ASIC has been tested in vivo and
      with standard public neural databases. MAIN RESULTS: Implemented using efficient
      digital circuit, this system is able to achieve >10 times data compression on the
      entire neural spike band (500-6KHz) while consuming only 0.83uW (0.53 V voltage
      supply) additional digital power per electrode. When only the spikes are desired,
      the system is able to further compress the detected spikes by around 16 times.
      Unlike other similar systems, the characteristic spikes and inter-spike data can
      both be recovered which guarantes a >95% spike classification success rate. The
      compression circuit occupied 0.11mm(2)/electrode in a 180nm CMOS process. The
      complete signal processing circuit consumes <16uW/electrode. SIGNIFICANCE: Power
      and area efficiency demonstrated by the system make it an ideal candidate for
      integration into large recording arrays containing thousands of electrode. Closed
      loop recording and reconstruction performance evaluation further improves the
      robustness of the compression method, thus making the system more practical for
      long term recording.

PMID- 25874928
TI  - The role of lipoprotein-associated phospholipase A2 in a murine model of
      experimental autoimmune uveoretinitis.
AB  - Macrophage activation is, in part, regulated via hydrolysis of oxidised low
      density lipoproteins by Lipoprotein-Associated phospholipase A2 (Lp-PLA2),
      resulting in increased macrophage migration, pro-inflammatory cytokine release
      and chemokine expression. In uveitis, tissue damage is mediated as a result of
      macrophage activation; hence inhibition of Lp-PLA2 may limit macrophage
      activation and protect the tissue. Utilising Lp-PLA2 gene-deficient (KO) mice and
      a pharmacological inhibitor of Lp-PLA2 (SB-435495) we aimed to determine the
      effect of Lp-PLA2 suppression in mediating retinal protection in a model of
      autoimmune retinal inflammation, experimental autoimmune uveoretinitis (EAU).
      Following immunisation with RBP-3 (IRBP) 1-20 or 161-180 peptides, clinical
      disease was monitored and severity assessed, infiltrating leukocytes were
      enumerated by flow cytometry and tissue destruction quantified by histology.
      Despite ablation of Lp-PLA2 enzyme activity in Lp-PLA2 KO mice or wild-type mice
      treated with SB-435495, the number of infiltrating CD45+ cells in the retina was
      equivalent to control EAU animals, and there was no reduction in disease
      severity. Thus, despite the reported beneficial effects of therapeutic Lp-PLA2
      depletion in a variety of vascular inflammatory conditions, we were unable to
      attenuate disease, show delayed disease onset or prevent progression of EAU in Lp
      PLA2 KO mice. Although EAU exhibits inflammatory vasculopathy there is no overt
      defect in lipid metabolism and given the lack of effect following Lp-PLA2
      suppression, these data support the hypothesis that sub-acute autoimmune
      inflammatory disease progresses independently of Lp-PLA2 activity. 

PMID- 25874930
TI  - Atorvastatin calcium inhibits phenotypic modulation of PDGF-BB-induced VSMCs via
      down-regulation the Akt signaling pathway.
AB  - Plasticity of vascular smooth muscle cells (VSMCs) plays a central role in the
      onset and progression of proliferative vascular diseases. In adult tissue, VSMCs
      exist in a physiological contractile-quiescent phenotype, which is defined by
      lack of the ability of proliferation and migration, while high expression of
      contractile marker proteins. After injury to the vessel, VSMC shifts from a
      contractile phenotype to a pathological synthetic phenotype, associated with
      increased proliferation, migration and matrix secretion. It has been demonstrated
      that PDGF-BB is a critical mediator of VSMCs phenotypic switch. Atorvastatin
      calcium, a selective inhibitor of 3-hydroxy-3-methyl-glutaryl l coenzyme A (HMG
      CoA) reductase, exhibits various protective effects against VSMCs. In this study,
      we investigated the effects of atorvastatin calcium on phenotype modulation of
      PDGF-BB-induced VSMCs and the related intracellular signal transduction pathways.
      Treatment of VSMCs with atorvastatin calcium showed dose-dependent inhibition of
      PDGF-BB-induced proliferation. Atorvastatin calcium co-treatment inhibited the
      phenotype modulation and cytoskeleton rearrangements and improved the expression
      of contractile phenotype marker proteins such as alpha-SM actin, SM22alpha and
      calponin in comparison with PDGF-BB alone stimulated VSMCs. Although Akt
      phosphorylation was strongly elicited by PDGF-BB, Akt activation was attenuated
      when PDGF-BB was co-administrated with atorvastatin calcium. In conclusion,
      atorvastatin calcium inhibits phenotype modulation of PDGF-BB-induced VSMCs and
      activation of the Akt signaling pathway, indicating that Akt might play a vital
      role in the modulation of phenotype. 

PMID- 25874931
TI  - Ultrahigh-density linkage map for cultivated cucumber (Cucumis sativus L.) using
      a single-nucleotide polymorphism genotyping array.
AB  - Genotyping arrays are tools for high-throughput genotyping, which is beneficial
      in constructing saturated genetic maps and therefore high-resolution mapping of
      complex traits. Since the report of the first cucumber genome draft, genetic maps
      have been constructed mainly based on simple-sequence repeats (SSRs) or on
      combinations of SSRs and sequence-related amplified polymorphism (SRAP). In this
      study, we developed the first cucumber genotyping array consisting of 32,864
      single-nucleotide polymorphisms (SNPs). These markers cover the cucumber genome
      with a median interval of ~2 Kb and have expected genotype calls in parents/F1
      hybridizations as a training set. The training set was validated with Fluidigm
      technology and showed 96% concordance with the genotype calls in the parents/F1
      hybridizations. Application of the genotyping array was illustrated by
      constructing a 598.7 cM genetic map based on a '9930' * 'Gy14' recombinant inbred
      line (RIL) population comprised of 11,156 SNPs. Marker collinearity between the
      genetic map and reference genomes of the two parents was estimated at R2 = 0.97.
      We also used the array-derived genetic map to investigate chromosomal
      rearrangements, regional recombination rate, and specific regions with
      segregation distortions. Finally, 82% of the linkage-map bins were polymorphic in
      other cucumber variants, suggesting that the array can be applied for genotyping
      in other lines. The genotyping array presented here, together with the genotype
      calls of the parents/F1 hybridizations as a training set, should be a powerful
      tool in future studies with high-throughput cucumber genotyping. An ultrahigh
      density linkage map constructed by this genotyping array on RIL population may be
      invaluable for assembly improvement, and for mapping important cucumber QTLs. 

PMID- 25874933
TI  - Correction: "hand down, man down." analysis of defensive adjustments in response
      to the hot hand in basketball using novel defense metrics.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0114184.]. 

PMID- 25874932
TI  - Brooding in the Chilean oyster Ostrea chilensis: unexpected complexity in the
      movements of brooded offspring within the mantle cavity.
AB  - Brooding in invertebrates serves to protect embryos from stressful external
      conditions by retaining progeny inside the female body, effectively reducing the
      risk of pelagic stages being exposed to predation or other environmental
      stressors, but with accompanying changes in pallial fluid characteristics,
      including reduced oxygen availability. Brooded embryos are usually immobile and
      often encapsulated, but in some Ostrea species the embryos move freely inside the
      female pallial cavity in close association with the mother's gills for as long as
      eight weeks. We used endoscopic techniques to characterize the circulation
      pattern of embryos brooded by females of the oyster, Ostrea chilensis. Progeny at
      embryonic and veliger stages typically circulated in established patterns that
      included the use of dorsal and ventral food grooves (DFG, VFG) to move anteriorly
      on the gills. Both embryos and veligers accumulated around the mother's palps,
      and remained there until an active maternal countercurrent moved them to the gill
      inhalant area. Both food grooves were able to move embryos, veligers, and food
      particle aggregates anteriorly, but the DFG was more important in progeny
      transport; early embryos were moved more rapidly than veligers in the DFG. A
      microcirculation pattern of embryos was apparent when they were moved by gill
      lamellae: when they were close to the VFG, most embryos lost gill contact and
      "fell" down to the DFG. Those that actually reached the DFG moved anteriorly, but
      others came into contact with the base of the lamellae and again moved towards
      the VFG. The circulation pattern of the progeny appears well-suited for both
      cleaning them and directing them posteriorly to an area where there is more
      oxygen and food than in the palp region. This process for actively circulating
      progeny involves the feeding structures (gill and palps) and appears to be
      energetically costly for the female. It also interferes with feeding, which could
      explain the poor energy balance previously documented for brooding females of
      this species.

PMID- 25874934
TI  - Rheostat re-wired: alternative hypotheses for the control of thioredoxin
      reduction potentials.
AB  - Thioredoxins are small soluble proteins that contain a redox-active disulfide
      (CXXC). These disulfides are tuned to oxidizing or reducing potentials depending
      on the function of the thioredoxin within the cell. The mechanism by which the
      potential is tuned has been controversial, with two main hypotheses: first, that
      redox potential (Em) is specifically governed by a molecular 'rheostat'-the XX
      amino acids, which influence the Cys pKa values, and thereby, Em; and second, the
      overall thermodynamics of protein folding stability regulates the potential.
      Here, we use protein film voltammetry (PFV) to measure the pH dependence of the
      redox potentials of a series of wild-type and mutant archaeal Trxs, PFV and
      glutathionine-equilibrium to corroborate the measured potentials, the
      fluorescence probe BADAN to measure pKa values, guanidinium-based denaturation to
      measure protein unfolding, and X-ray crystallography to provide a structural
      basis for our functional analyses. We find that when these archaeal thioredoxins
      are probed directly using PFV, both the high and low potential thioredoxins
      display consistent 2H+:2e- coupling over a physiological pH range, in conflict
      with the conventional 'rheostat' model. Instead, folding measurements reveals an
      excellent correlation to reduction potentials, supporting the second hypothesis
      and revealing the molecular mechanism of reduction potential control in the
      ubiquitous Trx family. 

PMID- 25874935
TI  - Neuroprotective effect of neuroserpin in oxygen-glucose deprivation- and
      reoxygenation-treated rat astrocytes in vitro.
AB  - Neuroserpin (NSP) reportedly exerts neuroprotective effects in cerebral ischemic
      animal models and patients; however, the mechanism of protection is poorly
      understood. We thus attempted to confirm neuroprotective effects of NSP on
      astrocytes in the ischemic state and then explored the relative mechanisms.
      Astrocytes from neonatal rats were treated with oxygen-glucose deprivation (OGD)
      followed by reoxygenation (OGD/R). To confirm the neuroprotective effects of NSP,
      we measured the cell survival rate, relative lactate dehydrogenase (LDH) release;
      we also performed morphological methods, namely Hoechst 33342 staining and
      Annexin V assay. To explore the potential mechanisms of NSP, the release of
      nitric oxide (NO) and TNF-alpha related to NSP administration were measured by
      enzyme-linked immunosorbent assay. The proteins related to the NF-kappaB, ERK1/2,
      and PI3K/Akt pathways were investigated by Western blotting. To verify the cause
      and-effect relationship between neuroprotection and the NF-kappaB pathway, a NF
      kappaB pathway inhibitor sc3060 was employed to observe the effects of NSP
      induced neuroprotection. We found that NSP significantly increased the cell
      survival rate and reduced LDH release in OGD/R-treated astrocytes. It also
      reduced NO/TNF-alpha release. Western blotting showed that the protein levels of
      p-IKKBalpha/beta and P65 were upregulated by the OGD/R treatment and such effects
      were significantly inhibited by NSP administration. The NSP-induced inhibition
      could be significantly reversed by administration of the NF-kappaB pathway
      inhibitor sc3060, whereas, expressions of p-ERK1, p-ERK2, and p-AKT were
      upregulated by the OGD/R treatment; however, their levels were unchanged by NSP
      administration. Our results thus verified the neuroprotective effects of NSP in
      ischemic astrocytes. The potential mechanisms include inhibition of the release
      of NO/TNF-alpha and repression of the NF-kappaB signaling pathways. Our data also
      indicated that NSP has little influence on the MAPK and PI3K/Akt pathways. 

PMID- 25874936
TI  - A protein deep sequencing evaluation of metastatic melanoma tissues.
AB  - Malignant melanoma has the highest increase of incidence of malignancies in the
      western world. In early stages, front line therapy is surgical excision of the
      primary tumor. Metastatic disease has very limited possibilities for cure.
      Recently, several protein kinase inhibitors and immune modifiers have shown
      promising clinical results but drug resistance in metastasized melanoma remains a
      major problem. The need for routine clinical biomarkers to follow disease
      progression and treatment efficacy is high. The aim of the present study was to
      build a protein sequence database in metastatic melanoma, searching for novel,
      relevant biomarkers. Ten lymph node metastases (South-Swedish Malignant Melanoma
      Biobank) were subjected to global protein expression analysis using two
      proteomics approaches (with/without orthogonal fractionation). Fractionation
      produced higher numbers of protein identifications (4284). Combining both
      methods, 5326 unique proteins were identified (2641 proteins overlapping). Deep
      mining proteomics may contribute to the discovery of novel biomarkers for
      metastatic melanoma, for example dividing the samples into two metastatic
      melanoma "genomic subtypes", ("pigmentation" and "high immune") revealed several
      proteins showing differential levels of expression. In conclusion, the present
      study provides an initial version of a metastatic melanoma protein sequence
      database producing a total of more than 5000 unique protein identifications. The
      raw data have been deposited to the ProteomeXchange with identifiers PXD001724
      and PXD001725. 

PMID- 25874937
TI  - Digital gene expression analysis of Microsporum canis exposed to berberine
      chloride.
AB  - Berberine, a natural isoquinoline alkaloid of many medicinal herbs, has an active
      function against a variety of microbial infections including Microsporum canis
      (M. canis). However, the underlying mechanisms are poorly understood. To study
      the effect of berberine chloride on M. canis infection, a Digital Gene Expression
      (DGE) tag profiling was constructed and a transcriptome analysis of the M. canis
      cellular responses upon berberine treatment was performed. Illumina/Hisseq
      sequencing technique was used to generate the data of gene expression profile,
      and the following enrichment analysis of Gene Ontology (GO) and Pathway function
      were conducted based on the data of transcriptome. The results of DGE showed that
      there were 8476945, 14256722, 7708575, 5669955, 6565513 and 9303468 tags
      respectively, which was obtained from M. canis incubated with berberine or
      control DMSO. 8,783 genes were totally mapped, and 1,890 genes have shown
      significant changes between the two groups. 1,030 genes were up-regulated and 860
      genes were down-regulated (P<0.05) in berberine treated group compared to the
      control group. Besides, twenty-three GO terms were identified by Gene Ontology
      functional enrichment analysis, such as calcium-transporting ATPase activity, 2
      oxoglutarate metabolic process, valine catabolic process, peroxisome and unfolded
      protein binding. Pathway significant enrichment analysis indicated 6 signaling
      pathways that are significant, including steroid biosynthesis, steroid hormone
      biosynthesis, Parkinson's disease, 2,4-Dichlorobenzoate degradation, and tropane,
      piperidine and Isoquinoline alkaloid biosynthesis. Among these, eleven selected
      genes were further verified by qRT-PCR. Our findings provide a comprehensive view
      on the gene expression profile of M. canis upon berberine treatment, and shed
      light on its complicated effects on M. canis.

PMID- 25874938
TI  - Auricular acupressure on specific points for hemodialysis patients with insomnia:
      a pilot randomized controlled trial.
AB  - OBJECTIVES: To assess the feasibility and acceptability of a randomized
      controlled trial compared auricular acupressure (AA) on specific acupoints with
      AA on non-specific acupoints for treating maintenance hemodialysis (MHD) patients
      with insomnia. METHODS: Sixty three (63) eligible subjects were randomly assigned
      into either AA group received AA on specific acupoints (n=32), or sham AA (SAA)
      group received AA on points irrelevant to insomnia treatment (n=31) for eight
      weeks. All participants were followed up for 12 weeks after treatments. The
      primary outcome was clinical response at eight weeks after randomization, defined
      as a reduction of Pittsburgh Sleep Quality Index (PSQI) global score by 3 points
      and more. RESULTS: Fifty-eight (58) participants completed the trial and five
      dropped out. Twenty participants in AA group (62.5%) and ten in SAA group (32.3%)
      responded to the eight-week interventions (chi2 = 5.77, P = 0.02). PSQI global
      score declined 3.75 +/- 4.36 (95%CI -5.32, -2.18) and 2.26 +/- 3.89 (95%CI -3.68,
      -0.83) in AA group and SAA group respectively. Three participants died during the
      follow-up period. No evidence supported their deaths were related to the AA
      intervention. No other adverse event was observed. CONCLUSION: Feasibility and
      logistics of patient recruitment, randomization procedure, blinding approach,
      interventions application and outcome assessment had been tested in this pilot
      trial. The preliminary data appeared to show a favorable result on AA treatment.
      A full-scale trial is warranted. TRIAL REGISTRATION: Chinese Clinical Trial
      Registry ChiCTR-TRC-12002272.

PMID- 25874941
TI  - Drug-DNA Interaction Studies of Acridone-Based Derivatives.
AB  - N10-alkylated 2-bromoacridones are a novel series of potent antitumor compounds.
      DNA binding studies of these compounds were carried out using spectrophotometric
      titrations, Circular dichroism (CD) measurements using Calf Thymus DNA (CT DNA).
      The binding constants were identified at a range of K=0.3 to 3.9*10(5) M(-1) and
      the percentage of hypochromism from the spectral titrations at 28-54%. This study
      has identified a compound 9 with the good binding affinity of K=0.39768*10(5) M(
      1) with CT DNA. Molecular dynamics (MD) simulations have investigated the changes
      in structural and dynamic features of native DNA on binding to the active
      compound 9. All the synthesized compounds have increased the uptake of
      Vinblastine in MDR KBChR-8-5 cells to an extent of 1.25- to1.9-fold than standard
      modulator Verapamil of similar concentration. These findings allowed us to draw
      preliminary conclusions about the structural features of 2-bromoacridones and
      further chemical enhancement will improve the binding affinity of the acridone
      derivatives to CT-DNA for better drug-DNA interaction. The molecular modeling
      studies have shown mechanism of action and the binding modes of the acridones to
      DNA.

PMID- 25874939
TI  - Host genetic variation influences gene expression response to rhinovirus
      infection.
AB  - Rhinovirus (RV) is the most prevalent human respiratory virus and is responsible
      for at least half of all common colds. RV infections may result in a broad
      spectrum of effects that range from asymptomatic infections to severe lower
      respiratory illnesses. The basis for inter-individual variation in the response
      to RV infection is not well understood. In this study, we explored whether host
      genetic variation is associated with variation in gene expression response to RV
      infections between individuals. To do so, we obtained genome-wide genotype and
      gene expression data in uninfected and RV-infected peripheral blood mononuclear
      cells (PBMCs) from 98 individuals. We mapped local and distant genetic variation
      that is associated with inter-individual differences in gene expression levels
      (eQTLs) in both uninfected and RV-infected cells. We focused specifically on
      response eQTLs (reQTLs), namely, genetic associations with inter-individual
      variation in gene expression response to RV infection. We identified local reQTLs
      for 38 genes, including genes with known functions in viral response (UBA7, OAS1,
      IRF5) and genes that have been associated with immune and RV-related diseases
      (e.g., ITGA2, MSR1, GSTM3). The putative regulatory regions of genes with reQTLs
      were enriched for binding sites of virus-activated STAT2, highlighting the role
      of condition-specific transcription factors in genotype-by-environment
      interactions. Overall, we suggest that the 38 loci associated with inter
      individual variation in gene expression response to RV-infection represent
      promising candidates for affecting immune and RV-related respiratory diseases. 

PMID- 25874940
TI  - Is surveillance colonoscopy necessary for patients with sporadic gastric
      hyperplastic polyps?
AB  - BACKGROUND: Gastric polyps, such as adenomas and hyperplastic polyps, can be
      found in various colonic polyposis syndromes. Unlike in sporadic gastric
      adenomas, in which the increased risk of colorectal neoplasia has been well
      characterized, information in sporadic gastric hyperplastic polyps was limited.
      AIM: To evaluate the association of sporadic gastric hyperplastic polyps with
      synchronous colorectal neoplasia in a large cohort. METHODS: Patients with
      sporadic gastric hyperplastic polyps who underwent colonoscopy simultaneously or
      within six months were consecutively enrolled. Each patient was compared with two
      randomly selected age and sex matched controls without gastric polyps who also
      underwent colonoscopy in the same period. Data of patients' demographics and
      characteristics of the gastrointestinal polyps were documented. RESULTS: A total
      of 261 cases in 118,576 patients who underwent esophagogastroduodenoscopy were
      diagnosed as sporadic gastric hyperplastic polyps, and 192 of 261 (73.6%)
      patients underwent colonoscopy. Colorectal neoplasias were identified in 46
      (24.0%) of 192 cases and in 40 (10.4%) of 384 controls (P<0.001). The mean size
      and distribution of colorectal neoplasias were not significantly different
      between the two groups. There was a significantly higher rate of colorectal
      adenoma (odds ratio [OR] 3.2, 95% confidence interval [CI] 1.9-5.3) in the
      gastric hyperplastic polyps group than in the control group, while the prevalence
      of colorectal cancer was similar in the two groups. Logistic regression analysis
      also suggested that the presence of gastric hyperplastic polyps (OR 2.5, 95% CI
      1.5-4.0) was an independent risk factor for colorectal neoplasias. CONCLUSION:
      The risk of colorectal adenoma increases in patients with sporadic gastric
      hyperplastic polyps, and surveillance colonoscopy for these patients should be
      considered.

PMID- 25874942
TI  - RNA-Binding Efficacy of N-Phenylbenzohydroxamic Acid: An Invitro and Insilico
      Approach.
AB  - RNA has attracted recent attention for its key role in gene expression and hence
      targeting by small molecules for therapeutic intervention. This study is aimed to
      elucidate the specificity of RNA binding affinity of parent compound of N
      arylhydroxamic acids series, N-phenylbenzohydroxamic acid trivially named as
      PBHA,C6H5NOH.C6H5C?O. The binding behavior was examined by various biophysical
      methods such as absorption, fluorescence, and viscosity measurements. Molecular
      docking was also done. The value of affinity constant and overall binding
      constant was calculated 5.79+/-0.03*10(4) M(-1) and K'=1.09+/-0.03*10(5) M(-1),
      respectively. The Stern-Volmer constant Ksv obtained was 2.28+/-0.04*10(4) M(-1).
      The compound (PBHA) shows a concentration-based enhancement of fluorescence
      intensity with increasing RNA concentration. Fluorescence quenching of PBHA-RNA
      complex in presence of K4 [Fe(CN)6] was also observed. Viscometric studies
      complimented the UV results where a continuous increase in relative viscosity of
      the RNA solution was observed with added optimal PBHA concentration. All the
      experimental evidences indicate that PBHA can strongly bind to RNA through an
      intercalative mode.

PMID- 25874943
TI  - Novel carboxaldehyde mediated synthetic pathway for 5'-amino adenosine analogues.
AB  - Modifications of the 5'-position of adenosine have been prepared via a novel 5'
      carboxaldehyde synthon. The described methodology should prove useful for making
      related compounds in which amine-derived moieties off the 5'-position of
      adenosine (or related nucleoside congeners) can be easily incorporated via
      reductive amination, especially for the incorporation of aromatic amines. 

PMID- 25874944
TI  - Nucleoside azide-alkyne cycloaddition reactions under solvothermal conditions or
      using copper vials in a ball mill.
AB  - Novel nucleoside analogues containing photoswitchable moieties were prepared
      using 'click' cycloaddition reactions between 5'-azido-5'-deoxythymidine and mono
      or bis-N-propargylamide-substituted azobenzenes. In solution, high to
      quantitative yields were achieved using 5 mol% Cu(I) in the presence of a
      stabilizing ligand. 'Click' reactions using the monopropargylamides were also
      effected in the absence of added cuprous salts by the application of liquid
      assisted grinding (LAG) in metallic copper reaction vials. Specifically, high
      speed vibration ball milling (HSVBM) using a 3/32" (2.38 mm) diameter copper ball
      (62 mg) at 60 Hz overnight in the presence of ethyl acetate lead to complete
      consumption of the 5'-azido nucleoside with clean conversion to the corresponding
      1,3-triazole.

PMID- 25874945
TI  - Design and synthesis of 2'-deoxy-2'-[(1,2,3)triazol-1-yl]uridines using click
      chemistry approach.
AB  - A series of novel nucleosides bearing a 1,2,3-triazole moiety at the 2'-position
      of the sugar moiety has been synthesized starting from 2'-azidouridine and using
      the copper (I)-catalyzed Huisgen-Sharpless-Meldal 1,3-dipolar cycloaddition
      reaction. The reactions proceeded in overall yield of 52-82% and gave almost
      exclusively the 1,4-disubstituted 1,2,3-triazoles. The 2'-azidouridine was
      synthesized from uridine in two steps, and reacted with a variety of differently
      substituted alkynes to give the desired 2'-triazole-substituted uridine
      derivatives. 

PMID- 25874946
TI  - Atypical protein kinase C zeta: potential player in cell survival and cell
      migration of ovarian cancer.
AB  - Ovarian cancer is one of the most aggressive gynaecological cancers, thus
      understanding the different biological pathways involved in ovarian cancer
      progression is important in identifying potential therapeutic targets for the
      disease. The aim of this study was to investigate the potential roles of Protein
      Kinase C Zeta (PRKCZ) in ovarian cancer. The atypical protein kinase C isoform,
      PRKCZ, is involved in the control of various signalling processes including cell
      proliferation, cell survival, and cell motility, all of which are important for
      cancer development and progression. Herein, we observe a significant increase in
      cell survival upon PRKCZ over-expression in SKOV3 ovarian cancer cells;
      additionally, when the cells are treated with small interference RNA (siRNA)
      targeting PRKCZ, the motility of SKOV3 cells decreased. Furthermore, we
      demonstrate that over-expression of PRKCZ results in gene and/or protein
      expression alterations of insulin-like growth factor 1 receptor (IGF1R) and
      integrin beta 3 (ITGB3) in SKOV3 and OVCAR3 cells. Collectively, our study
      describes PRKCZ as a potential regulatory component of the IGF1R and ITGB3
      pathways and suggests that it may play critical roles in ovarian tumourigenesis. 

PMID- 25874947
TI  - Presence of mycobacterial L-forms in human blood: Challenge of BCG vaccination.
AB  - Possible persistence of bacteria in human blood as cell wall deficient forms (L
      forms) represents a top research priority for microbiologists. Application of
      live BCG vaccine and L-form transformation of vaccine strain may display a new
      intriguing aspect concerning the opportunity for occurrence of unpredictable
      colonization inside the human body by unusual microbial life forms. L-form
      cultures were isolated from 141 blood samples of people previously vaccinated
      with BCG, none with a history of exposure to tuberculosis. Innovative methodology
      to access the unusual L-form elements derived from human blood was developed. The
      methodology outlines the path of transformation of non- cultivable L-form element
      to cultivable bacteria and their adaptation for growth in vitro. All isolates
      showed typical L-forms growth features ("fried eggs" colonies and biofilm).
      Electron microscopy revealed morphology evidencing peculiar characteristics of
      bacterial L-form population (cell wall deficient polymorphic elements of variable
      shape and size). Regular detection of acid fast bacteria in smears of isolated
      blood L-form cultures, led us to start their identification by using specific
      Mycobactrium spp. genetic tests. Forty five of 97 genetically tested blood
      cultures provided specific positive signals for mycobacteria, confirmed by at
      least one of the 3 specific assays (16S rRNA PCR; IS6110 Real Time PCR and
      spoligotyping). In conclusion, the obtained genetic evidence suggests that these
      L-forms are of mycobacterial origin. As the investigated people had been
      vaccinated with BCG, we can assume that the identified mycobacterial L-forms may
      be produced by persisting live BCG vaccine. 

PMID- 25874949
TI  - Correction: CD105 expression on CD34-negative spindle-shaped stromal cells of
      primary tumor is an unfavorable prognostic marker in early breast cancer
      patients.

PMID- 25874948
TI  - Differences in access to services in rural emergency departments of Quebec and
      Ontario.
AB  - INTRODUCTION: Rural emergency departments (EDs) are important safety nets for the
      20% of Canadians who live there. A serious problem in access to health care
      services in these regions has emerged. However, there are considerable geographic
      disparities in access to trauma center in Canada. The main objective of this
      project was to compare access to local 24/7 support services in rural EDs in
      Quebec and Ontario as well as distances to Levels 1 and 2 trauma centers.
      MATERIALS AND METHODS: Rural EDs were identified through the Canadian Healthcare
      Association's Guide to Canadian Healthcare Facilities. We selected hospitals with
      24/7 ED physician coverage and hospitalization beds that were located in rural
      communities. There were 26 rural EDs in Quebec and 62 in Ontario meeting these
      criteria. Data were collected from ministries of health, local health
      authorities, and ED statistics. Fisher's exact test, the t-test or Wilcoxon-Mann
      Whitney test, were performed to compare rural EDs of Quebec and Ontario. RESULTS:
      All selected EDs of Quebec and Ontario agreed to participate in the study. The
      number of EDs visits was higher in Quebec than in Ontario (19 322 +/- 6 275 vs 13
      446 +/- 8 056, p = 0.0013). There were no significant differences between Quebec
      and Ontario's local population and small town population density. Quebec's EDs
      have better access to advance imaging services such as CT scanner (77% vs 15%, p
      < .0001) and most the consultant support and ICU (92% vs 31%, p < .0001).
      Finally, more than 40% of rural EDs in Quebec and Ontario are more than 300 km
      away from Levels 1 and 2 trauma centers. CONCLUSIONS: Considering that Canada has
      a Universal health care system, the discrepancies between Quebec and Ontario in
      access to support services are intriguing. A nationwide study is justified to
      address this issue.

PMID- 25874950
TI  - Biphilic Organophosphorus Catalysis: Regioselective Reductive Transposition of
      Allylic Bromides via P(III)/P(V) Redox Cycling.
AB  - We report that a regioselective reductive transposition of primary allylic
      bromides is catalyzed by a biphilic organophosphorus (phosphetane) catalyst.
      Spectroscopic evidence supports the formation of a pentacoordinate (sigma(5)-P)
      hydridophosphorane as a key reactive intermediate. Kinetics experiments and
      computational modeling are consistent with a unimolecular decomposition of the
      sigma(5)-P hydridophosphorane via a concerted cyclic transition structure that
      delivers the observed allylic transposition and completes a novel P(III)/P(V)
      redox catalytic cycle. These results broaden the growing repertoire of reactions
      catalyzed within the P(III)/P(V) redox couple and suggest additional
      opportunities for organophosphorus catalysis in a biphilic mode. 

PMID- 25874951
TI  - A multicenter, randomized, double-blind, placebo-controlled trial of high-dose
      rebamipide treatment for low-dose aspirin-induced moderate-to-severe small
      intestinal damage.
AB  - BACKGROUND: Low-dose aspirin (LDA) frequently causes small bowel injury. While
      some drugs have been reported to be effective in treating LDA-induced small
      intestinal damage, most studies did not exclude patients with mild damage thought
      to be clinically insignificant. AIM: We conducted a multicenter, randomized,
      double-blind, placebo-controlled trial to assess the efficacy of a high dose of
      rebamipide, a gastroprotective drug, for LDA-induced moderate-to-severe
      enteropathy. METHODS: We enrolled patients who received 100 mg of enteric-coated
      aspirin daily for more than 3 months and were found to have more than 3 mucosal
      breaks (i.e., erosions or ulcers) in the small intestine by capsule endoscopy.
      Eligible patients were assigned to receive either rebamipide 300 mg (triple dose)
      3 times daily or placebo for 8 weeks in a 2:1 ratio. Capsule endoscopy was then
      repeated. The primary endpoint was the change in the number of mucosal breaks
      from baseline to 8 weeks. Secondary endpoints included the complete healing of
      mucosal breaks at 8 weeks and the change in Lewis score (an endoscopic score
      assessing damage severity) from baseline to 8 weeks. RESULTS: The study was
      completed by 38 patients (rebamipide group: n = 25, placebo group: n = 13). After
      8 weeks of treatment, rebamipide, but not placebo, significantly decreased the
      number of mucosal breaks (p = 0.046). While the difference was not significant (p
      = 0.13), the rate of complete mucosal break healing in the rebamipide group (32%,
      8 of 25) tended to be higher than that in the placebo group (7.7%, 1 of 13).
      Rebamipide treatment significantly improved intestinal damage severity as
      assessed by the Lewis score (p = 0.02), whereas placebo did not. The triple dose
      of rebamipide was well tolerated. CONCLUSIONS: High-dose rebamipide is effective
      for the treatment of LDA-induced moderate-to-severe enteropathy. TRIAL
      REGISTRATION: UMIN Clinical Trials Registry UMIN000003463.

PMID- 25874952
TI  - Young children's affective responses to another's distress: dynamic and
      physiological features.
AB  - Two descriptive studies set out a new approach for exploring the dynamic features
      of children's affective responses (sadness and interest-worry) to another's
      distress. In two samples (N(study1) = 75; N(study2) = 114), Kindergarten children
      were shown a video-vignette depicting another child in distress and the temporal
      pattern of spontaneous expressions were examined across the unfolding vignette.
      Results showed, in both study 1 and 2, that sadness and interest-worry had
      distinct patterns of elicitation across the events of the vignette narrative and
      there was little co-occurrence of these affects within a given child. Temporal
      heart rate changes (study 2) were closely aligned to the events of the vignette
      and, furthermore, affective responses corresponded to distinctive physiological
      response profiles. The implications of distinct temporal patterns of elicitation
      for the meaning of sadness and interest-worry are discussed within the framework
      of emotion regulation and empathy.

PMID- 25874954
TI  - President's message.

PMID- 25874953
TI  - Factors associated to vaccination against influenza among elderly in a large
      Brazilian metropolis.
AB  - BACKGROUND: This study aimed to estimate coverage and identify factors associated
      to vaccination against influenza in the elderly population. METHODS: The study
      design was cross-sectional and population based. Data was collected in 2010 by
      the Health, Well-Being and Aging Study. Sample consisted of 1,341 community
      dwelling elderly, in Sao Paulo, Brazil. Association between vaccination and
      covariates was evaluated by means of prevalence ratios estimated by Poisson
      regression models. RESULTS: Self-reported vaccination coverage was 74.2% (95%
      confidence interval: 71.3-76.9). Remaining physically active and having had
      recent interaction with health services, mainly with public units of healthcare,
      were the main incentives to increase vaccination coverage among the elderly;
      whereas lower age, living alone and absent interaction with health services were
      the main constraints to influenza vaccination at the community level. These
      covariates had already been reported to influence influenza vaccination of elders
      in previous years. CONCLUSION: Previous knowledge already available on the main
      constraints to influenza vaccination has not allowed to remove them. Influenza
      campaigns should be strengthened to increase vaccination coverage, especially in
      the group more reticent to vaccination. Instructing healthcare providers to
      recommend vaccine uptake is an important piece of this puzzle.

PMID- 25874955
TI  - Predictors and moderators of psychological changes during the treatment of
      adolescent bulimia nervosa.
AB  - This study examined predictors of psychological change among 80 adolescents with
      bulimia nervosa (BN) participating in a randomized-controlled trial comparing
      family-based treatment (FBT) to supportive psychotherapy (SPT). Psychological
      outcomes (cognitive eating disorder pathology, depression, and self-esteem) were
      explored at baseline, post-treatment, and 6-month follow-up. Multi-level growth
      models examined predictors of rate of change in psychological outcomes and
      moderators of treatment effects. All psychological outcomes improved through 6
      month follow-up (moderate to large effect sizes) across both treatments. Overall,
      few significant predictors were identified. Older adolescents had faster change
      in self-esteem relative to younger adolescents (p = 0.03). Adolescents taking
      psychotropic medication at baseline had faster change in eating concerns relative
      to adolescents not taking medication (p = 0.02). Age (p = 0.02) and baseline
      purging severity (p = 0.03) moderated the relationship between treatment
      condition and change in eating concerns, where younger adolescents and
      individuals with high baseline purging had greater change when treated with FBT
      relative to SPT. Age and purging did not significantly moderate change in other
      psychological outcomes. Bulimic symptom improvement did not predict change in
      psychological symptoms. Generally, FBT and SPT were equally efficacious with
      respect to psychological improvement, although FBT may be more efficacious in
      younger adolescents and those with more frequent purging.

PMID- 25874956
TI  - Comprehensive analysis of temporal alterations in cellular proteome of Bacillus
      subtilis under curcumin treatment.
AB  - Curcumin is a natural dietary compound with antimicrobial activity against
      various gram positive and negative bacteria. This study aims to investigate the
      proteome level alterations in Bacillus subtilis due to curcumin treatment and
      identification of its molecular/cellular targets to understand the mechanism of
      action. We have performed a comprehensive proteomic analysis of B. subtilis AH75
      strain at different time intervals of curcumin treatment (20, 60 and 120 min
      after the drug exposure, three replicates) to compare the protein expression
      profiles using two complementary quantitative proteomic techniques, 2D-DIGE and
      iTRAQ. To the best of our knowledge, this is the first comprehensive longitudinal
      investigation describing the effect of curcumin treatment on B. subtilis
      proteome. The proteomics analysis revealed several interesting targets such UDP-N
      acetylglucosamine 1-carboxyvinyltransferase 1, putative septation protein SpoVG
      and ATP-dependent Clp protease proteolytic subunit. Further, in silico pathway
      analysis using DAVID and KOBAS has revealed modulation of pathways related to the
      fatty acid metabolism and cell wall synthesis, which are crucial for cell
      viability. Our findings revealed that curcumin treatment lead to inhibition of
      the cell wall and fatty acid synthesis in addition to differential expression of
      many crucial proteins involved in modulation of bacterial metabolism. Findings
      obtained from proteomics analysis were further validated using 5-cyano-2,3
      ditolyl tetrazolium chloride (CTC) assay for respiratory activity, resazurin
      assay for metabolic activity and membrane integrity assay by potassium and
      inorganic phosphate leakage measurement. The gene expression analysis of selected
      cell wall biosynthesis enzymes has strengthened the proteomics findings and
      indicated the major effect of curcumin on cell division. 

PMID- 25874957
TI  - Effects of low-intensity pulsed ultrasound on new trabecular bone during bone
      tendon junction healing in a rabbit model: a synchrotron radiation micro-CT
      study.
AB  - This study was designed to evaluate the effects of low-intensity pulsed
      ultrasound on bone regeneration during the bone-tendon junction healing process
      and to explore the application of synchrotron radiation micro computed tomography
      in three dimensional visualization of the bone-tendon junction to evaluate the
      microarchitecture of new trabecular bone. Twenty four mature New Zealand rabbits
      underwent partial patellectomy to establish a bone-tendon junction injury model
      at the patella-patellar tendon complex. Animals were then divided into low
      intensity pulsed ultrasound treatment (20 min/day, 7 times/week) and placebo
      control groups, and were euthanized at week 8 and 16 postoperatively (n = 6 for
      each group and time point). The patella-patellar tendon specimens were harvested
      for radiographic, histological and synchrotron radiation micro computed
      tomography detection. The area of the newly formed bone in the ultrasound group
      was significantly greater than that of control group at postoperative week 8 and
      16. The high resolution three dimensional visualization images of the bone-tendon
      junction were acquired by synchrotron radiation micro computed tomography. Low
      intensity pulsed ultrasound treatment promoted dense and irregular woven bone
      formation at week 8 with greater bone volume fraction, number and thickness of
      new trabecular bone but with lower separation. At week 16, ultrasound group
      specimens contained mature lamellar bone with higher bone volume fraction and
      thicker trabeculae than that of control group; however, there was no significant
      difference in separation and number of the new trabecular bone. This study
      confirms that low-intensity pulsed ultrasound treatment is able to promote bone
      formation and remodeling of new trabecular bone during the bone-tendon junction
      healing process in a rabbit model, and the synchrotron radiation micro computed
      tomography could be applied for three dimensional visualization to quantitatively
      evaluate the microarchitecture of new bone in bone-tendon junction.

PMID- 25874958
TI  - Grafting triggers differential responses between scion and rootstock.
AB  - Grafting is a well-established practice to facilitate asexual propagation in
      horticultural and agricultural crops. It has become a method for studying
      molecular aspects of root-to-shoot and/or shoot-to-root signaling events. The
      objective of this study was to investigate differences in gene expression between
      the organs of the scion and rootstock of a homograft (Arabidopsis thaliana).
      MapMan and Gene Ontology enrichment analysis revealed differentially expressed
      genes from numerous functional categories related to stress responses in the
      developing flower buds and leaves of scion and rootstock. Meta-analysis suggested
      induction of drought-type responses in flower buds and leaves of the scion. The
      flower buds of scion showed over-representation of the transcription factor
      genes, such as Homeobox, NAC, MYB, bHLH, B3, C3HC4, PLATZ etc. The scion leaves
      exhibited higher accumulation of the regulatory genes for flower development,
      such as SEPALLATA 1-4, Jumonji C and AHL16. Differential transcription of genes
      related to ethylene, gibberellic acid and other stimuli was observed between
      scion and rootstock. The study is useful in understanding the molecular basis of
      grafting and acclimation of scion on rootstock. 

PMID- 25874959
TI  - Co-delivery of baicalein and doxorubicin by hyaluronic acid decorated
      nanostructured lipid carriers for breast cancer therapy.
AB  - PURPOSE: Combination anticancer therapy is promising to generate synergistic
      anticancer effects, to maximize the treatment effect and to overcome multi-drug
      resistance. Nanostructured lipid carriers (NLCs), composed of solid and liquid
      lipids, and surfactants are potentially good colloidal drug carriers. The aim of
      this study is to construct a hyaluronic acid (HA) decorated NLCs as nanocarriers
      for co-delivery baicalein (BCL) and doxorubicin (DOX). METHODS: BCL- and DOX
      loaded NLCs (BCL/DOX-NLCs) were prepared. HA ligands were used for the decoration
      of BCL/DOX-NLCs to form HA decorated BCL/DOX-NLCs (HA-BCL/DOX-NLCs). The in vitro
      cytotoxicity studies of different formulations were evaluated on DOX drug
      resistant MCF-7 breast cancer cell line (MCF-7/ADR cells). In vivo anti-tumor
      effects were observed on the murine bearing MCF-7/ADR cells model. RESULTS: HA
      BCL/DOX-NLCs showed highest cytotoxicity and synergistic effect of two drugs in
      tumor cells in vitro. The in vivo study revealed the greatest anti-tumor activity
      than all the other formulations in the murine breast cancer model. CONCLUSIONS:
      HA decorated NLCs could be used as a novel carrier to co-delivery BCL and DOX for
      breast cancer therapy. HA-BCL/DOX-NLCs could be a promising targeted and
      combinational therapy nanomedicine.

PMID- 25874960
TI  - Ring planarity problem of 2-oxazoline revisited using microwave spectroscopy and
      quantum chemical calculations.
AB  - In a previous infrared, Raman, and microwave spectroscopic work,1 it was claimed
      that 2-oxazoline has a planar ring equilibrium conformation, and the ring
      puckering potential function V(z) = 22.2(z(4) + 1.31z(2)) cm(-1), where z is a
      dimensionless reduced coordinate, was derived. This function poorly reproduces
      the rotational constants of the lowest and most important puckering states. The
      microwave spectrum has been reinvestigated and largely extended to include more
      than 4600 transitions of the ground state and six excited states of the ring
      puckering vibration allowing accurate centrifugal distortion constants to be
      obtained for the first time. A new potential function V(z) = 38.8(z(4) -
      0.65z(2)) cm(-1) has been determined. This function yields much better agreement
      between calculated and observed rotational constants, especially for the lowest
      puckering states, than the previous function and predicts a nonplanar ring
      equilibrium conformation. The barrier to ring planarity is determined to be 49(8)
      J/mol. The ground-state energy level is 35 cm(-1) above the barrier maximum.
      Theory predicts that three of the five Watson centrifugal distortion constants,
      DeltaJK, DeltaK, and deltaK, should vary with the puckering state, whereas DeltaJ
      and deltaJ should be unaffected. It was found that DeltaJK and DeltaK indeed
      behave in the expected manner, while deviations were seen for the three other
      centrifugal distortion constants. The ab initio methods HF, MP2, CCSD, CCSD(T),
      and CCSD(T)-F12 with large basis sets as well as several DFT methods were used in
      an attempt to reproduce the low experimental barrier to the planar ring. Only the
      MP2 method yielded a satisfactory prediction of the barrier. The CCSD and the
      CCSD(T) calculations predict a planar ring, whereas the energy differences
      between a planar and a nonplanar ring obtained in the CCSD(T)-F12 computations
      are so small that a definite conclusion cannot be drawn. 

PMID- 25874961
TI  - Minocycline for Recurrent and/or Chronic Erythema Nodosum Leprosum.

PMID- 25874962
TI  - The use of alendronate is associated with a decreased incidence of type 2
      diabetes mellitus--a population-based cohort study in Taiwan.
AB  - PURPOSE: Bone remodeling has been linked to glucose metabolism in animal studies,
      but the results of human trials were inconclusive. Bisphosphonates may play a
      role in glucose metabolism through their impacts on bone remodeling enzymes. In
      this study, we aimed to examine the influence of alendronate usage on the
      incidence of type 2 diabetes mellitus (DM) among osteoporotic patients. METHODS:
      A retrospective cohort study was designed to include osteoporotic patients
      without DM from a population-based cohort containing 1,000,000 subjects. Patients
      treated with alendronate (exposed group, N=1,011) were compared with those who
      received no treatment (age and gender matched non-exposed group, N=3,033). Newly
      diagnosed DM was identified from medical records by International Classification
      of Diseases, Ninth Revision, Clinical Modification (ICD-9CM) code. The incidence
      of DM in both groups was calculated for comparison. RESULTS: The non-exposed
      group had a significantly higher incidence of DM (Odds ratio 1.21, 95% confidence
      interval 1.03~1.41) when compared with the exposed group. In subgroup analysis,
      the DM risk reduction in exposed group was only significant among those younger
      than 65 years and those without hypertension or dyslipidemia. Patients who were
      prescribed alendronate more than or equal to 3 times had demonstrated a
      significant reduction in DM risk. CONCLUSIONS: Our study showed alendronate might
      yield a protective effect for incident DM. This effect became insignificant in
      patients with older age, dyslipidemia or hypertension. The underlying mechanism
      needs further exploration with prospective data for confirmation of the observed
      findings.

PMID- 25874963
TI  - Threatened Caribbean coral is able to mitigate the adverse effects of ocean
      acidification on calcification by increasing feeding rate.
AB  - Global climate change threatens coral growth and reef ecosystem health via ocean
      warming and ocean acidification (OA). Whereas the negative impacts of these
      stressors are increasingly well-documented, studies identifying pathways to
      resilience are still poorly understood. Heterotrophy has been shown to help
      corals experiencing decreases in growth due to either thermal or OA stress;
      however, the mechanism by which it mitigates these decreases remains unclear.
      This study tested the ability of coral heterotrophy to mitigate reductions in
      growth due to climate change stress in the critically endangered Caribbean coral
      Acropora cervicornis via changes in feeding rate and lipid content. Corals were
      either fed or unfed and exposed to elevated temperature (30 degrees C), enriched
      pCO2 (800 ppm), or both (30 degrees C/800 ppm) as compared to a control (26
      degrees C/390 ppm) for 8 weeks. Feeding rate and lipid content both increased in
      corals experiencing OA vs. present-day conditions, and were significantly
      correlated. Fed corals were able to maintain ambient growth rates at both
      elevated temperature and elevated CO2, while unfed corals experienced significant
      decreases in growth with respect to fed conspecifics. Our results show for the
      first time that a threatened coral species can buffer OA-reduced calcification by
      increasing feeding rates and lipid content. 

PMID- 25874964
TI  - DNA detection of Schistosoma japonicum: diagnostic validity of a LAMP assay for
      low-intensity infection and effects of chemotherapy in humans.
AB  - BACKGROUND: Schistosomiasis has decreased significantly in prevalence and
      intensity of infection in China, thus more accurate and sensitive methods are
      desperately needed for the further control of schistosomiasis. The present work
      aimed to assess the utility of the loop-mediated isothermal amplification (LAMP)
      for detection of light intensity infection or false-negative patients and
      patients post-treatment, targeting the highly repetitive retrotransposon SjR2 of
      Schistosoma japonicum. METHODOLOGY/ PRINCIPAL FINDINGS: LAMP was first assessed
      in rabbits with low intensity infection (EPG<10). Then 110 patient sera from
      Hunan Province, China, and 47 sera after treatment by praziquantel were used to
      evaluate the diagnostic validity of LAMP. Meanwhile, 42 sera from healthy
      individuals in a non-endemic area, and 60 sera from "healthy" residents who were
      identified as being negative for feces examination and immuno-methods in an
      endemic area were also examined. The results showed that LAMP could detect S.
      japonicum DNA in sera from rabbits at 3rd day post-infection. Following
      administration of praziquantel, the S. japonicum DNA in rabbit sera became
      negative at 10 weeks post-treatment. Of 110 sera from patients, LAMP showed 95.5%
      sensitivity, and even for 41 patients with less than 10 EPG, the sensitivity of
      LAMP still reached to 95.1%. For 47 patients after treatment, the negative
      conversion rate of S. japonicum DNA in patient sera increased from 23.4%, 61.7%
      to 83.0% at 3 months, 6 months and 9 months post-treatment, respectively. No
      false-positive result was obtained for 42 human sera from non-endemic area, while
      for the 60 "healthy" individuals from endemic area, 10 (16.7%) individuals were
      positive by LAMP, which suggested that these individuals might be false-negative
      patients. CONCLUSIONS/ SIGNIFICANCE: The present study demonstrated that the LAMP
      assay is sensitive, specific, and affordable, which would help reduce
      schistosomiasis transmission through targeted treatment of individuals,
      particularly for those with negative stool examinations who may yet remain
      infected. The LAMP assay may provide a potential tool to support schistosomiasis
      control and elimination strategies.

PMID- 25874966
TI  - Memory detection 2.0: the first web-based memory detection test.
AB  - There is accumulating evidence that reaction times (RTs) can be used to detect
      recognition of critical (e.g., crime) information. A limitation of this research
      base is its reliance upon small samples (average n = 24), and indications of
      publication bias. To advance RT-based memory detection, we report upon the
      development of the first web-based memory detection test. Participants in this
      research (Study1: n = 255; Study2: n = 262) tried to hide 2 high salient
      (birthday, country of origin) and 2 low salient (favourite colour, favourite
      animal) autobiographical details. RTs allowed to detect concealed
      autobiographical information, and this, as predicted, more successfully so than
      error rates, and for high salient than for low salient items. While much remains
      to be learned, memory detection 2.0 seems to offer an interesting new platform to
      efficiently and validly conduct RT-based memory detection research. 

PMID- 25874965
TI  - Antagonism of angiotensin 1-7 prevents the therapeutic effects of recombinant
      human ACE2.
AB  - Activation of the angiotensin 1-7/Mas receptor (MasR) axis counteracts
      angiotensin II (Ang II)-mediated cardiovascular disease. Recombinant human
      angiotensin-converting enzyme 2 (rhACE2) generates Ang 1-7 from Ang II. We
      hypothesized that the therapeutic effects of rhACE2 are dependent on Ang 1-7
      action. Wild type male C57BL/6 mice (10-12 weeks old) were infused with Ang II
      (1.5 mg/kg/d) and treated with rhACE2 (2 mg/kg/d). The Ang 1-7 antagonist, A779
      (200 ng/kg/min), was administered to a parallel group of mice. rhACE2 prevented
      Ang II-induced hypertrophy and diastolic dysfunction while A779 prevented these
      beneficial effects and precipitated systolic dysfunction. rhACE2 effectively
      antagonized Ang II-mediated myocardial fibrosis which was dependent on the action
      of Ang 1-7. Myocardial oxidative stress and matrix metalloproteinase 2 activity
      was further increased by Ang 1-7 inhibition even in the presence of rhACE2.
      Activation of Akt and endothelial nitric oxide synthase (eNOS) by rhACE2 were
      suppressed by the antagonism of Ang 1-7 while the activation of pathological
      signaling pathways was maintained. Blocking Ang 1-7 action prevents the
      therapeutic effects of rhACE2 in the setting of elevated Ang II culminating in
      systolic dysfunction. These results highlight a key cardioprotective role of Ang
      1-7, and increased Ang 1-7 action represents a potential therapeutic strategy for
      cardiovascular diseases. KEY MESSAGES: Activation of the renin-angiotensin system
      (RAS) plays a key pathogenic role in cardiovascular disease. ACE2, a
      monocarboxypeptidase, negatively regulates pathological effects of Ang II.
      Antagonizing Ang 1-7 prevents the therapeutic effects of recombinant human ACE2.
      Our results highlight a key protective role of Ang 1-7 in cardiovascular disease.

PMID- 25874967
TI  - Rapid review programs to support health care and policy decision making: a
      descriptive analysis of processes and methods.
AB  - BACKGROUND: Health care decision makers often need to make decisions in limited
      timeframes and cannot await the completion of a full evidence review. Rapid
      reviews (RRs), utilizing streamlined systematic review methods, are increasingly
      being used to synthesize the evidence with a shorter turnaround time. Our primary
      objective was to describe the processes and methods used internationally to
      produce RRs. In addition, we sought to understand the underlying themes
      associated with these programs. METHODS: We contacted representatives of
      international RR programs from a broad realm in health care to gather information
      about the methods and processes used to produce RRs. The responses were
      summarized narratively to understand the characteristics associated with their
      processes and methods. The summaries were compared and contrasted to highlight
      potential themes and trends related to the different RR programs. RESULTS: Twenty
      nine international RR programs were included in our sample with a broad
      organizational representation from academia, government, research institutions,
      and non-for-profit organizations. Responses revealed that the main objectives for
      RRs were to inform decision making with regards to funding health care
      technologies, services and policy, and program development. Central themes that
      influenced the methods used by RR programs, and report type and dissemination
      were the imposed turnaround time to complete a report, resources available, the
      complexity and sensitivity of the research topics, and permission from the
      requestor. CONCLUSIONS: Our study confirmed that there is no standard approach to
      conduct RRs. Differences in processes and methods across programs may be the
      result of the novelty of RR methods versus other types of evidence syntheses,
      customization of RRs for various decision makers, and definition of 'rapid' by
      organizations, since it impacts both the timelines and the evidence synthesis
      methods. Future research should investigate the impact of current RR methods and
      reporting to support informed health care decision making, the effects of
      potential biases that may be introduced with streamlined methods, and the
      effectiveness of RR reporting guidelines on transparency.

PMID- 25874968
TI  - Carbon nanotube-polyamidoamine dendrimer hybrid-modified electrodes for highly
      sensitive electrochemical detection of microRNA24.
AB  - A simple and ultrasensitive microRNA (miRNA) electrochemical biosensor employing
      multiwalled carbon nanotube (MWCNT)-polyamidoamine (PAMAM) dendrimer and
      methylene blue (MB) redox indicator is reported in this work. The assay utilizes
      a glass carbon (GC) electrode modified with MWCNT-PAMAM, on which the
      oligonucleotide capture probes are immobilized. The electrochemical detection of
      miRNAs is completed by measuring the reduction signal change of MB before and
      after the probe hybridization with target miRNA (miRNA24 is used as a model
      case). The MWCNT-PAMAM/GC electrode shows greatly enhanced signal to MB reduction
      in contrast to bare GC electrode. The functionalization of MWCNT with PAMAM
      maintains the electrochemical property of MWCNT to MB reduction but minimizes the
      undesired adsorption of MB on the MWCNT surface. The effect of experimental
      variables on the miRNA detection is investigated and optimized. A detection limit
      of 0.5 fM and a linear peak current density-concentration relationship up to 100
      nM are obtained following 60 min hybridization. The proposed assay is
      successfully used to detect miRNA24 in total RNA sample extracted from HeLa
      cells. 

PMID- 25874969
TI  - Comparison of audio and audiovisual measures of adult stuttering: Implications
      for clinical trials.
AB  - PURPOSE: This study investigated whether measures of percentage syllables
      stuttered (%SS) and stuttering severity ratings with a 9-point scale differ when
      made from audiovisual compared with audio-only recordings. METHOD: Four
      experienced speech-language pathologists measured %SS and assigned stuttering
      severity ratings to 10-minute audiovisual and audio-only recordings of 36 adults.
      RESULT: There was a mean 18% increase in %SS scores when samples were presented
      in audiovisual compared with audio-only mode. This result was consistent across
      both higher and lower %SS scores and was found to be directly attributable to
      counts of stuttered syllables rather than the total number of syllables. There
      was no significant difference between stuttering severity ratings made from the
      two modes. CONCLUSION: In clinical trials research, when using %SS as the primary
      outcome measure, audiovisual samples would be preferred as long as clear, good
      quality, front-on images can be easily captured. Alternatively, stuttering
      severity ratings may be a more valid measure to use as they correlate well with
      %SS and values are not influenced by the presentation mode.

PMID- 25874970
TI  - Provision of dysphagia services in a developing nation: Infrastructural
      challenges.
AB  - PURPOSE: The purpose of the current study was to explore infrastructure issues
      that may be barriers to the establishment and improvement of dysphagia services
      in Malaysia compared to settings with established dysphagia management services
      (i.e. Queensland, Australia). METHOD: A mixed method design incorporating
      quantitative and qualitative data was used to increase credibility, validity and
      comprehensiveness of the results. Thirty-eight hospitals (Malaysia = 21,
      Queensland = 17) participated in Phase 1 (quantitative component) of the study
      involving completion of an infrastructure checklist by a speech-language
      pathologist from each hospital regarding availability of networking and
      communication, staffing and financial support, facilities and documentation of
      guidelines for dysphagia management. Subsequently, eight sub-samples from each
      cohort were then involved in Phase 2 (qualitative component) of the study
      involving a semi-structured interview on issues related to the impact of
      infrastructure availability or constraints on service provision. RESULT: The
      current study reveals that multiple challenges exist with regard to dysphagia
      services in Malaysian government hospitals compared to Queensland public
      hospitals. CONCLUSION: Overall, it was identified that service improvement in
      Malaysia requires change at a systems and structures level, but also, more
      importantly, at the individual/personal level, particularly focusing on the
      culture, behaviour and attitudes among the staff regarding dysphagia services.

PMID- 25874972
TI  - A novel three-dimensional spherical CuBi2O4 consisting of nanocolumn arrays with
      persulfate and peroxymonosulfate activation functionalities for 1H-benzotriazole
      removal.
AB  - A novel CuBi2O4 consisting of self-assembled spherical nanocolumn arrays (CuB-H)
      was synthesized via a facile hydrothermal method. It was further modified by
      controlling the Cu : Bi ratio during synthesis to become an efficient bi
      functional catalyst (CuB-2.5) activated persulfate (PS) and peroxymonosulfate
      (PMS) for 1H-benzotriazole (BTZ) removal. Characterization of CuB-2.5 using XRD,
      FESEM, FTIR, BET and XPS revealed that it was morphologically similar to CuB-H
      and the molecular formula, as determined from the XRD results, was Cu1.2Bi1.6O3.6
      with 2.4% w/w of CuO. The CuB-2.5 catalyst exhibited superior performance for BTZ
      removal via PS and PMS activations over the Cu(2+) (aq.), CuO, CuBi2O4 (CuB-M,
      microsphere) and CuB-H. The performance of CuB-2.5 was investigated at different
      initial PS/PMS dosages, initial catalyst loadings and initial BTZ concentrations.
      Interestingly, it was found that the inter- and intra-molecular hydrogen bondings
      play prominent roles in the BTZ removal mechanism in both the PS and PMS systems.
      Meanwhile, it is relatively easy to activate PMS, leading to a faster BTZ removal
      rate over the PS system. The intermediate products of BTZ degradation produced
      from the PS and PMS systems were similar, indicating a similar degradation
      pathway. The catalyst could still retain its morphology and can be reused
      multiple times. 

PMID- 25874971
TI  - Vaginal deployment and tenofovir delivery by microbicide gels.
AB  - Gels are one of the soft material platforms being evaluated to deliver topically
      acting anti-HIV drugs (microbicides) to the vaginal environment. For each drug,
      its loaded concentration, gel properties and applied volume, and frequency of
      dosing can be designed to optimize PK and, thence, PD. These factors also impact
      user sensory perceptions and acceptability. Deterministic compartmental modeling
      of vaginal deployment and drug delivery achieved by test gels can help delineate
      how multiple parameters characterizing drug, vehicle, vaginal environment, and
      dosing govern details of PK and PD and also gel leakage from the canal. Such
      microbicide delivery is a transport process combining convection, e.g., from gel
      spreading along the vaginal canal, with drug diffusion in multiple compartments,
      including gel, mucosal epithelium, and stroma. The present work builds upon prior
      models of gel coating flows and drug diffusion (without convection) in the
      vaginal environment. It combines and extends these initial approaches in several
      key ways, including: (1) linking convective drug transport due to gel spreading
      with drug diffusion and (2) accounting for natural variations in dimensions of
      the canal and the site of gel placement therein. Results are obtained for a
      leading microbicide drug, tenofovir, delivered by three prototype microbicide
      gels, with a range of rheological properties. The model includes phosphorylation
      of tenofovir to tenofovir diphosphate (which manifests reverse transcriptase
      activity in host cells), the stromal concentration distributions of which are
      related to reference prophylactic values against HIV. This yields a computed
      summary measure related to gel protection ("percent protected"). Analyses
      illustrate tradeoffs amongst gel properties, drug loading, volume and site of
      placement, and vaginal dimensions, in the time and space history of gel
      distribution and tenofovir transport to sites of its anti-HIV action and
      concentrations and potential prophylactic actions of tenofovir diphosphate
      therein. 

PMID- 25874974
TI  - A hybrid gel-solid-state polymer electrolyte for long-life lithium oxygen
      batteries.
AB  - A hybrid gel-solid-state polymer electrolyte has been used as the separator and
      an electrolyte for lithium oxygen batteries. It can not only avoid electrolyte
      evaporation but also protect the lithium metal anode during reactions over long
      term cycling. Due to its high ionic conductivity and low activation energy,
      excellent cycling performance is demonstrated, in which the terminal voltage is
      higher than 2.2 V after 140 cycles at 0.4 mA cm(-2), with a capacity of 1000 mA h
      g(composite)(-1). 

PMID- 25874975
TI  - Responses of plant community composition and biomass production to warming and
      nitrogen deposition in a temperate meadow ecosystem.
AB  - Climate change has profound influences on plant community composition and
      ecosystem functions. However, its effects on plant community composition and
      biomass production are not well understood. A four-year field experiment was
      conducted to examine the effects of warming, nitrogen (N) addition, and their
      interactions on plant community composition and biomass production in a temperate
      meadow ecosystem in northeast China. Experimental warming had no significant
      effect on plant species richness, evenness, and diversity, while N addition
      highly reduced the species richness and diversity. Warming tended to reduce the
      importance value of graminoid species but increased the value of forbs, while N
      addition had the opposite effect. Warming tended to increase the belowground
      biomass, but had an opposite tendency to decrease the aboveground biomass. The
      influences of warming on aboveground production were dependent upon
      precipitation. Experimental warming had little effect on aboveground biomass in
      the years with higher precipitation, but significantly suppressed aboveground
      biomass in dry years. Our results suggest that warming had indirect effects on
      plant production via its effect on the water availability. Nitrogen addition
      significantly increased above- and below-ground production, suggesting that N is
      one of the most important limiting factors determining plant productivity in the
      studied meadow steppe. Significant interactive effects of warming plus N addition
      on belowground biomass were also detected. Our observations revealed that
      environmental changes (warming and N deposition) play significant roles in
      regulating plant community composition and biomass production in temperate meadow
      steppe ecosystem in northeast China. 

PMID- 25874977
TI  - Feasibility of asymmetric flow field-flow fractionation coupled to ICP-MS for the
      characterization of wear metal particles and metalloproteins in biofluids from
      hip replacement patients.
AB  - Hip replacements are used to improve the quality of life of people with
      orthopaedic conditions, but the use of metal-on-metal (MoM) arthroplasty has led
      to poor outcomes for some patients. These problems are related to the generation
      of micro- to nanosized metal wear particles containing Cr, Co or other elements,
      but the current analytical methods used to investigate the processes involved do
      not provide sufficient information to understand the size or composition of the
      wear particles generated in vivo. In this qualitative feasibility study,
      asymmetric flow field-flow fractionation (AF(4)) coupled with inductively coupled
      plasma mass spectrometry (ICP-MS) was used to investigate metal protein binding
      and the size and composition of wear metal particles present in serum and hip
      aspirates from MoM hip replacement patients. A well-established HPLC anion
      exchange chromatography (AEC) separation system coupled to ICP-MS was used to
      confirm the metal-protein associations in the serum samples. Off-line single
      particle ICP-MS (spICP-MS) analysis was used to confirm the approximate size
      distribution indicated by AF(4) of the wear particles in hip aspirates. In the
      serum samples, AF(4) -ICP-MS suggested that Cr was associated with transferrin
      (Tf) and Co with albumin (Alb) and an unidentified species; AEC-ICP-MS confirmed
      these associations and also indicated an association of Cr with Alb. In the hip
      aspirate sample, AF(4)-ICP-MS suggested that Cr was associated with Alb and Tf
      and that Co was associated with Alb and two unidentified compounds; AEC analysis
      confirmed the Cr results and the association of Co with Alb and a second
      compound. Enzymatic digestion of the hip aspirate sample, followed by separation
      using AF(4) with detection by UV absorption (280 nm), multi-angle light
      scattering and ICP-MS, suggested that the sizes of the Cr-, Co- and Mo-containing
      wear particles in a hip aspirate sample were in the range 40-150 nm. Off-line
      spICP-MS was used to confirm these findings for the Co- and Cr-containing
      nanoparticles. Whilst limited in scope, the results are sufficient to show the
      interaction of ions with transport proteins and give an indication of particle
      size, providing useful pathological indices. As such, the methods indicate a new
      way forward for in vivo investigation of the processes which lead to tissue
      necrosis and hip loosening in patients with MoM hip replacements. 

PMID- 25874978
TI  - AIDS communications through social networks: catalyst for behaviour changes in
      Uganda.
AB  - OBJECTIVE: To investigate distinctive communications through social networks
      which may be associated with population behaviour changes and HIV prevalence
      declines in Uganda compared to other countries. METHODS: We undertook a
      comparative analysis of demographic and HIV behavioural data collected in
      Demographic and Health Surveys (DHS III) in Uganda, Kenya, Tanzania, Malawi,
      Zambia and Zimbabwe as well as Knowledge, Attitudes and Behaviours (KABP) surveys
      in Uganda in 1989 and 1995. AIDS behaviours, social communications and channels
      for communication about AIDS and people with AIDS were analysed by age, sex and
      country. Modelling was developed to investigate at what stage of the epidemic a
      majority of people will know someone with AIDS, given differing communication
      patterns through social networks. Finally AIDS reporting and Voluntary
      Counselling and Testing (VCT) trends were analysed to assess if the impact of
      social communications worked through clinical services and interventions or more
      directly at the population level in community contexts. RESULTS: Uganda showed
      unique patterns of communications through social networks including a shift from
      mass and institutional to personal channels for communicating about AIDS, 1989
      1995. This was associated with higher levels of knowing someone with AIDS through
      social networks and, in turn, positive risk ratios for behaviour change including
      reducing casual sex and condom use. Youth had distinctively high levels of
      knowing someone with AIDS in Uganda, suggesting widespread community
      communication across age groups. Patterns of disclosure, AIDS diagnosis and
      reporting were influential on social communications about AIDS. Over 90%, 45% or
      under 20% of people know someone with AIDS at peak HIV incidence and high AIDS
      mortality, depending on whether communications through social networks are
      extensive or restricted. CONCLUSION: There are distinctive patterns for
      communicating through social networks about AIDS and people with AIDS in Uganda.
      They appear to work directly at population level rather than in response to
      clinical interventions and testing and may be important in the uptake of the
      latter services. This communication response provides an important basis for HIV
      prevention if it is to be scaled to the population level. Vertical prevention
      (and even treatment) interventions need to engage more closely with local,
      horizontal communication and behavioural responses to AIDS. Communication
      programmes have to take root at the level of social networks working though local
      networks of meetings, chiefs, churches and health personnel as well as the media.
      Mobilising basic social communications may be a necessary resource (as much as
      services and finance) to scale HIV prevention and treatment to the population
      level.

PMID- 25874976
TI  - ALK kinase domain mutations in primary anaplastic large cell lymphoma:
      consequences on NPM-ALK activity and sensitivity to tyrosine kinase inhibitors.
AB  - ALK inhibitor crizotinib has shown potent antitumor activity in children with
      refractory Anaplastic Large Cell Lymphoma (ALCL) and the opportunity to include
      ALK inhibitors in first-line therapies is oncoming. However, recent studies
      suggest that crizotinib-resistance mutations may emerge in ALCL patients. In the
      present study, we analyzed ALK kinase domain mutational status of 36 paediatric
      ALCL patients at diagnosis to identify point mutations and gene aberrations that
      could impact on NPM-ALK gene expression, activity and sensitivity to small
      molecule inhibitors. Amplicon ultra-deep sequencing of ALK kinase domain detected
      2 single point mutations, R335Q and R291Q, in 2 cases, 2 common deletions of exon
      23 and 25 in all the patients, and 7 splicing-related INDELs in a variable number
      of them. The functional impact of missense mutations and INDELs was evaluated.
      Point mutations were shown to affect protein kinase activity, signalling output
      and drug sensitivity. INDELs, instead, generated kinase-dead variants with
      dominant negative effect on NPM-ALK kinase, in virtue of their capacity of
      forming non-functional heterocomplexes. Consistently, when co-expressed, INDELs
      increased crizotinib inhibitory activity on NPM-ALK signal processing, as
      demonstrated by the significant reduction of STAT3 phosphorylation. Functional
      changes in ALK kinase activity induced by both point mutations and structural
      rearrangements were resolved by molecular modelling and dynamic simulation
      analysis, providing novel insights into ALK kinase domain folding and regulation.
      Therefore, these data suggest that NPM-ALK pre-therapeutic mutations may be found
      at low frequency in ALCL patients. These mutations occur randomly within the ALK
      kinase domain and affect protein activity, while preserving responsiveness to
      crizotinib. 

PMID- 25874979
TI  - AIDS as chronic illness: epidemiological transition and health care in south
      eastern Botswana.
AB  - This paper suggests that people in south-eastern Botswana experience the AIDS
      epidemic as part of a recent epidemiological transition in which rates of chronic
      debilitating illness have risen, even as the degree of acute infectious disease
      has fallen (HIV/AIDS aside). Whereas international health programmes and
      practitioners focus on AIDS as an acute, lethal, infectious disease, patients and
      care-givers experience AIDS as a set of chronic, degenerative (and deadly)
      conditions. This is true whether or not patients know or acknowledge their HIV
      status. Neither the national health system nor the Tswana medical sector
      (bongaka) cope well with the particular issues that chronic illnesses present.
      Thus, the epidemiological context of the AIDS epidemic in Botswana is critical to
      understanding uneven patient confidence in a comparatively robust health system. 

PMID- 25874980
TI  - Malawi faith communities responding to HIV/AIDS: preliminary findings of a
      knowledge translation and Participatory-Action Research (PAR) project.
AB  - This paper reports on the preliminary findings (year one) of a four-year
      intervention and Participatory-Action Research (PAR) project in Malawi. Project
      goals are to enhance the response capacity and effectiveness of Faith Community
      (FC) leaders to the problem of HIV/AIDS. Ethnographic interviews with FC leaders
      were conducted. Intercultural training sessions and theological events were also
      held using a participatory method called conceptual events. Preliminary results
      indicate a commitment on the part of faith community leaders to enter into a
      dialogue with other sectors and faith traditions in addressing the common,
      critical concern of HIV/AIDS. All FC leaders share a common feeling that they are
      a small moral voice in this fight against HIV/AIDS, drowned out by a 'big voice'
      promoting condom use by donors and government. FC leaders are expected to present
      themselves as having an authoritative voice with respect to protecting the soul,
      but at the same time are sincerely searching for ways to speak about HIV/AIDS in
      more practical ways. Condoms become a metaphor for resistance. For example, FC
      leaders wish to know how the message of condom promotion (a behavioural and
      technical argument) might be grafted onto what they would posit as a moral
      message of care, prevention and support. This challenge is made even more complex
      by the quiet assumption to incorporate the truths of African traditional religion
      (ATR) in the construction of an ecumenical theology of faith, hope and
      compassion. 

PMID- 25874981
TI  - Children and youth at risk: adaptation and pilot study of the CHAMP (Amaqhawe)
      programme in South Africa.
AB  - This paper reports on the adaptation and pilot study of the CHAMP programme
      (Collaborative HIV/AIDS and Adolescent Mental Health Programme) in South Africa
      with specific reference to outcome effects among adults. CHAMP was originally
      developed in the United States and is a developmentally-timed intervention, which
      aims to prevent HIV infection in youth through promoting resiliency in pre
      adolescents and their families as well as strengthening the community protective
      shield. The adaptation was informed by a focused ethnographic study of the risk
      influences for HIV transmission in adolescents at the individual,
      family/interpersonal and community levels within the study site and achieved
      through a collaborative partnership of academics, community members, graphic
      artists and service providers. The CHAMP programme in South Africa (Amaqhawe)
      employs participatory adult education principles, including a participatory
      cartoon-based narrative method to deliver its content. Proximal outcome effects
      of the pilot study demonstrate positive effects amongst the parent participants
      at the individual and interpersonal/family levels of influence compared to the
      comparison group indicating the potential applicability of the CHAMP programme in
      South Africa. 

PMID- 25874982
TI  - Using an undertaker's data to assess changing patterns of mortality and their
      consequences in Swaziland.
AB  - This paper measures AIDS mortality using routinely collected data from one of two
      nationally operating undertakers in Swaziland. The business recorded a marked
      increase in the number of deaths it handled between 1998 and 2002, most obvious
      in the 0-4 and 20-49 age categories. Cost data reflects this increase in
      mortality. Prices for funerals and coffins have declined in real terms. Recorded
      causes of death were of little use in determining the extent of AIDS mortality.
      This was due to stigma and denial, the relatively small number of people dying in
      hospitals and lack of accurate reporting of medical diagnoses. Key informant
      interviews were done to support the undertaker's data and determine how families
      bear the burden of burying deceased relatives. Despite a disproportionate
      increase in deaths in certain age categories and evidence of worsening poverty,
      funerals remain large and elaborate affairs. 

PMID- 25874983
TI  - Sex during genital bleeding and risks for HIV infection: preliminary study of
      sexually transmitted infection clinic patients in Cape Town, South Africa.
AB  - Practicing sexual intercourse in the presence of blood is a potentially important
      factor in facilitating HIV transmission. In the current study 149 men and 78
      women receiving diagnostic and treatment services for repeated sexually
      transmitted infections (STI) in Cape Town, South Africa, provided behavioural
      data on sexual exposure to blood. Results showed that 46% of women and 12% of men
      reported lifetime prevalence of engaging in sexual intercourse while their
      genitals were bleeding and 7% of women and 40% of men reported sexual intercourse
      with a partner whose genitals were bleeding; 27% of men and 22% of women had
      engaged in sexual intercourse with blood present within the previous month.
      Individuals who had engaged in sexual intercourse involving blood had
      significantly greater numbers of sex partners in the previous month, engaged in
      higher rates of unprotected vaginal intercourse and total anal intercourse
      occasions during that time period. Engaging in sex during genital bleeding was
      also related to greater lifetime prevalence of sexually transmitted infections
      and unexplained genital discharge. These findings add to the growing evidence
      that exposure to blood during vaginal intercourse may be prevalent and may be an
      important contributing factor to the rapid spread of HIV in Southern Africa. 

PMID- 25874984
TI  - HIV/AIDS, poverty and risky sexual behaviour in South Africa.
AB  - This paper employs data from the 1998 South African Demographic and Health Survey
      in exploring the nature of socio-economic inequalities in and determinants of
      risky sexual behaviour. Risky sexual behaviour was associated with poverty only
      in the case of multiple partnerships. Affluent women that have engaged in risky
      sexual behaviour were shown to be more likely to have cited negative perceptions
      about condom use as main reason for not using a condom at last sex. Poor women in
      turn were more likely to cite lack of knowledge about condoms and abstinence from
      condom use as main reason. Poverty plays little part in explaining differences in
      risky sexual behaviour, although higher education in some cases was associated
      positively with risky sexual behaviour. Risky sexual behaviour was associated
      with differences in age, urban residence and marital status. Coloured, Asian and
      White women were less likely than African women to have engaged in risky sexual
      behaviour. Violence and coercion were also associated with risky sexual
      behaviour. Women in affluent households that had engaged in risky sexual
      behaviour were more likely to have been mistreated by a husband or partner
      compared to poor women. There is no evidence of a definitive one-way causal
      relationship between poverty, gender and sexual behaviour and further research is
      required to elucidate this complex relationship. 

PMID- 25874985
TI  - Willingness to care for children orphaned by HIV/AIDS: a study of foster and
      adoptive parents.
AB  - There is substantial evidence to indicate that South Africa is facing the
      prospect of a large number of children, now and in the future, who will be
      orphaned as a result of the HIV/AIDS pandemic. Following the incapacitation
      and/or death of their parents, many of these children will be cared for by the
      safety net provided by members of their extended families. However, there is
      evidence to suggest that this safety net is fast becoming overwhelmed and
      possibly reaching saturation point. The ideal would be for as many of these
      children as possible to experience some type of family life in which to grow and
      mature into responsible adults. The present study explores adoptive and foster
      parents' (n = 175) willingness to care for a child orphaned by HIV/AIDS. Although
      some differences were noted depending on the HIV status of the child and whether
      the respondent was an adoptive or foster parent, results indicate an overall
      willingness in these populations to care for children orphaned by HIV/AIDS. The
      evidence also suggests that HIV-negative female orphans who are younger than 6
      years, and who are family members, or from the same cultural background as the
      potential caregivers and do not have surviving relatives or siblings, have the
      best chance of being taken into foster or adoptive care. 

PMID- 25874986
TI  - 'Kusvika taparadzaniswa nerufu' (Until death do us part).
AB  - A cross-sectional study of 7 667 non-virgins between 15 and 54 years of age was
      carried out to assess the protective effect of marriage against HIV acquisition
      in a rural population in Zimbabwe, whilst taking into account gender
      differentials in risk factors for seroconversion. Persons in stable first
      marriages and long-term consensual cohabiting unions had higher odds of HIV
      infection than never-married people but a lower risk than those who had been
      divorced or widowed, even after adjusting for known confounders and significant
      risk factors for infection. Partner-related risk factors appear to play a more
      pivotal role in determining HIV prevalence in females than for males, for whom
      personal sexual behaviour risk factors are more dominant. 

PMID- 25874987
TI  - The development and evaluation of a manualised participatory HIV/AIDS risk
      reduction programme (Sex and Risk) for tertiary level learners: a pilot study.
AB  - This paper reports on a pilot study of the development and evaluation (using
      outcome and process measures) of a manualised participatory risk reduction
      programme, aimed at reducing high-risk sexual behaviour amongst tertiary level
      learners, called 'Sex and Risk' (S&R), at the University of Durban-Westville 1 in
      South Africa. The programme was grounded in a focused ethnographic study of the
      risk behaviours and life context of tertiary level learners at this institution,
      as well as informed by literature on successful behavioural risk reduction
      programmes on Western and African populations. Significantly, the S&R programme
      was shown to facilitate greater awareness in males of how social influences
      inform high-risk sexual behaviour. This greater awareness did not, however,
      translate into greater self-efficacy in relation to negotiating safer sexual
      relationships for either males or females and was attributed to the dominant
      social norms, which promote and sustain gender inequity that places the sexual
      health of young women and men at risk. Given that the S&R programme operates
      largely at the level of the individual, although it does address the subjective
      aspects of social influences on behaviour, these findings highlight the need for
      proximal situation-centred interventions, which promote more egalitarian social
      norms in sexual relationships, to accompany such curriculum interventions at
      tertiary institutions. 

PMID- 25874988
TI  - Letting Them Die: How HIV/AIDS Prevention Programmes Often Fail Catherine
      Campbell.

PMID- 25874990
TI  - Cerebral function in perinatally HIV-infected young adults and their HIV
      uninfected sibling controls.
AB  - BACKGROUND: Perinatally acquired HIV-infected (PaHIV) young adults undergo
      neurodevelopment in the presence of HIV infection and antiretroviral therapy,
      which may lead to neurocognitive (NC) impairment. Knowledge of NC function in
      this group is sparse and control data lacking. We compared cerebral function in
      young adults with PaHIV infection to aged matched HIV negative family controls.
      METHODS: 16-25-year-old PaHIV young adults (Group 1, n = 33) and HIV-uninfected
      family controls (Group 2, n = 14) were recruited. Cerebral function was evaluated
      by: a computerized battery assessing NC function (CogState(TM)), International
      HIV Dementia Scale (IHDS) and the prospective and retrospective memory
      questionnaire (PRMQ). Eight cases and four controls also underwent (1)H cerebral
      magnetic resonance spectroscopy ((1)H-MRS) scanning measuring basal ganglia (BG)
      metabolites. Cases and controls were compared. RESULTS: Group 1 mean (SD) CD4
      count; 444 (319) cells/MUl, plasma HIV viral load < 50 in 55%. There were no
      statistically significant differences between study groups in NC function or IHDS
      results (P>0.27 all observations). PRMQ scores were significantly higher (42
      versus 35, P = 0.02) and MRS BG inflammatory-metabolites (choline- and myo
      inositol- to creatine ratios) were significantly greater in Group 1 versus Group
      2 (0.83 versus 0.63, P = 0.02 and 3.43 versus 3.03.P = 0.09 respectively). No
      significant association between PRMQ score and MRS metabolites was observed (P =
      0.89). CONCLUSION: Statistically significant differences in cerebral function
      parameters were observed in PaHIV young adults compared to a well-matched control
      population. The cognitive deficit observed, in memory, rather than fine motor
      function, differs from the cerebral impairment often reported in HIV-infected
      adults.

PMID- 25874989
TI  - Functional characterization of the vitamin K2 biosynthetic enzyme UBIAD1.
AB  - UbiA prenyltransferase domain-containing protein 1 (UBIAD1) plays a significant
      role in vitamin K2 (MK-4) synthesis. We investigated the enzymological properties
      of UBIAD1 using microsomal fractions from Sf9 cells expressing UBIAD1 by
      analysing MK-4 biosynthetic activity. With regard to UBIAD1 enzyme reaction
      conditions, highest MK-4 synthetic activity was demonstrated under basic
      conditions at a pH between 8.5 and 9.0, with a DTT >=0.1 mM. In addition, we
      found that geranyl pyrophosphate and farnesyl pyrophosphate were also recognized
      as a side-chain source and served as a substrate for prenylation. Furthermore,
      lipophilic statins were found to directly inhibit the enzymatic activity of
      UBIAD1. We analysed the aminoacid sequences homologies across the menA and UbiA
      families to identify conserved structural features of UBIAD1 proteins and focused
      on four highly conserved domains. We prepared protein mutants deficient in the
      four conserved domains to evaluate enzyme activity. Because no enzyme activity
      was detected in the mutants deficient in the UBIAD1 conserved domains, these four
      domains were considered to play an essential role in enzymatic activity. We also
      measured enzyme activities using point mutants of the highly conserved aminoacids
      in these domains to elucidate their respective functions. We found that the
      conserved domain I is a substrate recognition site that undergoes a structural
      change after substrate binding. The conserved domain II is a redox domain site
      containing a CxxC motif. The conserved domain III is a hinge region important as
      a catalytic site for the UBIAD1 enzyme. The conserved domain IV is a binding site
      for Mg2+/isoprenyl side-chain. In this study, we provide a molecular mapping of
      the enzymological properties of UBIAD1. 

PMID- 25874991
TI  - Tripterygium wilfordii Hook F extract in cART-treated HIV patients with poor
      immune response: a pilot study to assess its immunomodulatory effects and safety.
AB  - BACKGROUND: Despite combination antiretroviral therapy (cART), 20% of HIV
      infected patients are unable to achieve adequate immunologic recovery, in which
      immune activation plays a crucial role. We hypothesize that extract of
      Tripterygium wilfordii Hook F (TwHF), a Chinese medication used to treat
      autoimmune diseases, has immunomodulatory effects that may help CD4 cell
      recovery. METHODS: Eighteen cART-treated HIV-infected patients virally suppressed
      for over 12 months with suboptimal CD4 cell recovery were enrolled. TwHF extract
      was administered at a dosage of 10 mg three times daily for 12 months. T-cell
      subsets and activation markers were evaluated at baseline and during follow-up.
      The trial was registered at Clinicaltrials.gov (NCT02002286). RESULTS: TwHF
      extract was associated with a mean increase in CD4 cell count of 88 cells/MUl
      (95% confidential interval [CI], 72-105 cells/MUl) after one year of treatment. A
      significant increase in the mean rate of CD4 cell recovery (26 before vs 75
      cells/MUl/year after TwHF use, P < 0.001) was observed. Analysis of 13 patients
      with activation profiles suggested that TwHF extract was associated with a
      decrease in T-cell immune activation which was temporally correlated with CD4
      cell recovery. No discontinuation of TwHF extract was reported. CONCLUSION: Use
      of TwHF extract in HIV-infected patients was associated with a reduction in T
      cell activation and improved CD4 recovery with an excellent safety profile.

PMID- 25874992
TI  - Cardiovascular risk factors and lifetime risk estimation in HIV-infected patients
      under antiretroviral treatment in Spain.
AB  - BACKGROUND AND OBJECTIVES: Cardiovascular disease is a major concern in HIV
      infected patients. Lifetime risk estimations use the risk of developing it over
      the course of remaining lifetime, and are useful in communicating this risk to
      young patients. We aim to describe the prevalence of cardiovascular risk factors
      among a representative sample of HIV-infected subjects under antiretroviral
      therapy in Spain, and to estimate their lifetime risk of cardiovascular disease.
      METHODS: Cross-sectional survey about cardiovascular risk factors in 10 HIV units
      across Spain. Lifetime risk assessed according to Barry was classified in two
      major categories: low and high lifetime risk. RESULTS: We included 895 subjects,
      72% men, median age 45.7 years; median CD4 lymphocyte count 598 cells/MUl, median
      time since HIV diagnosis 11 years, median time on antiretroviral treatment 6.3
      years, 87% had undetectable HIV viral load. Tobacco smoking was the most frequent
      risk factor (54%), followed by dyslipidemia (48.6%) and hypertension (38.6%).
      Estimated 10-year coronary risk (Framingham/Regicor Risk Score) risk was low ( <
      5%) in 78% of the patients, and intermediate (5-10%) in 20%. Lifetime risk
      estimation showed a high risk profile for 71.4% of the population studied, which
      was associated with increasing age, prolonged antiretroviral therapy and
      patient's place of origin. CONCLUSIONS: Modifiable cardiovascular risk factors in
      this population are very common. There are significant disparities between the
      low 10-year risk estimated with the Framingham/Regicor score and the higher
      lifetime risk in HIV patients on antiretroviral therapy. A more aggressive
      management of modifiable cardiovascular risk factors in these patients seems
      advisable.

PMID- 25874993
TI  - Low cost facile synthesis of large-area cobalt hydroxide nanorods with remarkable
      pseudocapacitance.
AB  - Large-area Co(OH)2-based supercapacitor electrodes composed of nanotube arrays
      grown on a 3D nickel-foam (CONTA) electrode and sucker-like nanoporous films
      grown on a 3D nickel-foam (COSNP) electrode were prepared with a facile
      electrochemical method for applications in energy storage. These nanoporous
      Co(OH)2 electrodes were fabricated with the codeposition of Cu/Ni film on the
      nickel foam, then etching of Cu from the Cu/Ni layer to form Ni nanotube arrays
      and sucker-like Ni nanoporous layers, and further cathodic deposition of Co(OH)2
      on the prepared nanoporous Ni substrates. The CONTA and COSNP electrodes
      exhibited specific capacitances of 2500 and 2900 F/g in a voltage range of 0.65 V
      (capacitance of the substrates deducted from the total) at 1 A/g in a three
      electrode cell, respectively. The COSNP electrode demonstrated an excellent
      supercapacitive performance with specific capacitances 1100 F/g at 1 A/g and 850
      F/g at 20 A/g in a voltage range of 1.2 V in a two electrode cell. The remarkable
      performance of COSNP electrodes correlated with a large conversion of the Co
      oxidation state during the charge/discharge cycling were examined by in situ X
      ray absorption near edge structure (XANES). 

PMID- 25874994
TI  - An adaptive biointerface from self-assembled functional peptides for tissue
      engineering.
AB  - A self-assembled peptide-based biointerface is demonstrated with triple
      functional layers that can significantly improve the tissue self-healing process
      or prevent biofilm-mediated chronic inflammation. This smart biointerface is
      composed of three functional moieties (i.e., a cell-adhesive peptide, an
      infectious environment-responsive peptide, and an antifouling hexaethylene glycol
      (HEG) layer), and the resulting interface coated onto prosthetic replacements can
      smartly respond to the surrounding physiological or pathological
      microenvironment. 

PMID- 25874995
TI  - Tabersonine inhibits amyloid fibril formation and cytotoxicity of Abeta(1-42).
AB  - The misfolding and aggregation of amyloid beta (Abeta) peptides into amyloid
      fibrils are key events in the amyloid cascade hypothesis for the etiology of
      Alzheimer's disease (AD). Using thioflavin-T (ThT) fluorescence assay, atomic
      force microscopy, circular dichroism, size exclusion chromatography, surface
      plasmon resonance (SPR), and cytotoxicity tests, we demonstrate that tabersonine,
      an ingredient extracted from the bean of Voacanga africana, disrupts Abeta(1-42)
      aggregation and ameliorates Abeta aggregate-induced cytotoxicity. A small amount
      of tabersonine (e.g., 10 MUM) can effectively inhibit the formation of Abeta(1
      42) (e.g., 80 MUM) fibrils or convert mature fibrils into largely innocuous
      amorphous aggregates. SPR results indicate that tabersonine binds to Abeta(1-42)
      oligomers in a dose-dependent way. Molecular dynamics (MD) simulations further
      confirm that tabersonine can bind to oligomers such as the pentamer of Abeta(1
      42). Tabersonine preferentially interact with the beta-sheet grooves of Abeta(1
      42) containing aromatic and hydrophobic residues. The various binding sites and
      modes explain the diverse inhibitory effects of tabersonine on Abeta aggregation.
      Given that tabersonine is a natural product and a precursor for vincristine used
      in cancer chemotherapy, the biocompatibility and small size essential for
      permeating the blood-brain barrier make it a potential therapeutic drug candidate
      for treating AD. 

PMID- 25874996
TI  - Bacterial genotoxins promote inside-out integrin beta1 activation, formation of
      focal adhesion complexes and cell spreading.
AB  - Integrins are membrane bound receptors that regulate several cellular processes,
      such as cell adhesion, migration, survival and proliferation, and may contribute
      to tumor initiation/progression in cells exposed to genotoxic stress. The extent
      of integrin activation and its role in cell survival upon intoxication with
      bacterial genotoxins are still poorly characterized. These toxins induce DNA
      strand breaks in the target cells and activate the DNA damage response (DDR),
      coordinated by the Ataxia Telangectasia Mutated (ATM) kinase. In the present
      study, we demonstrate that induction of DNA damage by two bacterial genotoxins
      promotes activation of integrin beta1, leading to enhanced assembly of focal
      adhesions and cell spreading on fibronectin, but not on vitronectin. This
      phenotype is mediated by an ATM-dependent inside-out integrin signaling, and
      requires the actin cytoskeleton remodeler NET1. The toxin-mediated cell spreading
      and anchorage-independent survival further relies on ALIX and TSG101, two
      components of the endosomal sorting complex required for transport (ESCRT), known
      to regulate integrin intracellular trafficking. These data reveal a novel aspect
      of the cellular response to bacterial genotoxins, and provide new tools to
      understand the carcinogenic potential of these effectors in the context of
      chronic intoxication and infection. 

PMID- 25874997
TI  - Population census of a large common tern colony with a small unmanned aircraft.
AB  - Small unmanned aircraft systems (UAS) may be useful for conducting high
      precision, low-disturbance waterbird surveys, but limited data exist on their
      effectiveness. We evaluated the capacity of a small UAS to census a large (>6,000
      nests) coastal Common tern (Sterna hirundo) colony of which ground surveys are
      particularly disruptive and time-consuming. We compared aerial photographic tern
      counts to ground nest counts in 45 plots (5-m radius) throughout the colony at
      three intervals over a nine-day period in order to identify sources of variation
      and establish a coefficient to estimate nest numbers from UAS surveys. We also
      compared a full colony ground count to full counts from two UAS surveys conducted
      the following day. Finally, we compared colony disturbance levels over the course
      of UAS flights to matched control periods. Linear regressions between aerial and
      ground counts in plots had very strong correlations in all three comparison
      periods (R2 = 0.972-0.989, P < 0.001) and regression coefficients ranged from
      0.928-0.977 terns/nest. Full colony aerial counts were 93.6% and 94.0%,
      respectively, of the ground count. Varying visibility of terns with ground cover,
      weather conditions and image quality, and changing nest attendance rates
      throughout incubation were likely sources of variation in aerial detection rates.
      Optimally timed UAS surveys of Common tern colonies following our method should
      yield population estimates in the 93-96% range of ground counts. Although the
      terns were initially disturbed by the UAS flying overhead, they rapidly
      habituated to it. Overall, we found no evidence of sustained disturbance to the
      colony by the UAS. We encourage colonial waterbird researchers and managers to
      consider taking advantage of this burgeoning technology. 

PMID- 25874998
TI  - Prevalence of post-stroke cognitive impairment in china: a community-based, cross
      sectional study.
AB  - International hospital-based studies have indicated a high risk of cognitive
      impairment after stroke, evidence from community-based studies in China is
      scarce. To determine the prevalence of post-stroke cognitive impairment (PSCI)
      and its subtypes in stroke survivors residing in selected rural and urban Chinese
      communities, we conducted a community-based, cross-sectional study in 599
      patients accounting for 48% of all stroke survivors registered in the 4
      communities, who had suffered confirmed strokes and had undergone cognitive
      assessments via the Montreal Cognitive Assessment (MoCA), Mini-Mental State
      Examination (MMSE), and Hachinski Ischemia Scale (HIS). Detection of PSCI was
      based on scores in these neuropsychological scales. Factors potentially impacting
      on occurrence of PSCI were explored by comparing demographic characteristics,
      stroke features, and cardiovascular risk factors between patients with and
      without PSCI. The overall prevalence of PSCI was 80.97% (95%CI: 77.82%-84.11%),
      while that of non-dementia PSCI (PSCI-ND) and post-stroke vascular dementia (PSD)
      was 48.91% (95%CI: 44.91%-52.92%) and 32.05% (95%CI: 28.32%-35.79%),
      respectively. Prior stroke and complications during the acute phase were
      independent risk factors for PSCI. The risk of recurrent stroke survivors having
      PSCI was 2.7 times higher than for first-episode survivors, and it was 3 times
      higher for those with complications during the acute phase than for those
      without. The higher prevalence of PSCI in this study compared with previous
      Chinese studies was possibly due to the combined effects of including rural
      stroke survivors, a longer period from stroke onset, and different assessment
      methods. There is an urgent need to recognize and prevent PSCI in stroke
      patients, especially those with recurrent stroke and complications during the
      acute phase. 

PMID- 25874999
TI  - Correction: Ras and Rac1, frequently mutated in melanomas, are activated by
      superoxide anion, modulate Dnmt1 level and are causally related to melanocyte
      malignant transformation.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0081937.]. 

PMID- 25875000
TI  - Neurofunctional correlates of environmental cognition: an FMRI study with images
      from episodic memory.
AB  - This study capitalizes on individual episodic memories to investigate the
      question, how dif-ferent environments affect us on a neural level. Instead of
      using predefined environmental stimuli, this study relied on individual
      representations of beauty and pleasure. Drawing upon episodic memories we
      conducted two experiments. Healthy subjects imagined pleasant and non-pleasant
      environments, as well as beautiful and non-beautiful environments while neural
      activity was measured by using functional Magnetic Resonance Imaging. Although
      subjects found the different conditions equally simple to visualize, our results
      revealed more distribut-ed brain activations for non-pleasant and non-beautiful
      environments than for pleasant and beautiful environments. The additional regions
      activated in non-pleasant (left lateral prefrontal cortex) and non-beautiful
      environments (supplementary motor area, anterior cortical midline structures) are
      involved in self-regulation and top-down cognitive control. Taken together, the
      results show that perceptual experiences and emotional evaluations of
      environments within a positive and a negative frame of reference are based on
      distinct patterns of neural activity. We interpret the data in terms of a
      different cognitive and processing load placed by exposure to different
      environments. The results hint at the efficiency of subject-generated
      representations as stimulus material. 

PMID- 25875002
TI  - Correction: imputation of the rare HOXB13 G84E mutation and cancer risk in a
      large population-based cohort.

PMID- 25875001
TI  - Changes in brain network efficiency and working memory performance in aging.
AB  - Working memory is a complex psychological construct referring to the temporary
      storage and active processing of information. We used functional connectivity
      brain network metrics quantifying local and global efficiency of information
      transfer for predicting individual variability in working memory performance on
      an n-back task in both young (n = 14) and older (n = 15) adults. Individual
      differences in both local and global efficiency during the working memory task
      were significant predictors of working memory performance in addition to age (and
      an interaction between age and global efficiency). Decreases in local efficiency
      during the working memory task were associated with better working memory
      performance in both age cohorts. In contrast, increases in global efficiency were
      associated with much better working performance for young participants; however,
      increases in global efficiency were associated with a slight decrease in working
      memory performance for older participants. Individual differences in local and
      global efficiency during resting-state sessions were not significant predictors
      of working memory performance. Significant group whole-brain functional network
      decreases in local efficiency also were observed during the working memory task
      compared to rest, whereas no significant differences were observed in network
      global efficiency. These results are discussed in relation to recently developed
      models of age-related differences in working memory. 

PMID- 25875003
TI  - Functional assembly of protein fragments induced by spatial confinement.
AB  - Natural proteins are often confined within their local microenvironments, such as
      three-dimensional confinement in organelles or two-dimensional confinement in
      lipid rafts on cytoplasmic membrane. Spatial confinement restricts proteins'
      entropic freedom, forces their lateral interaction, and induces new properties
      that the same proteins lack at the soluble state. So far, the phenomenon of
      environment-induced protein functional alteration still lacks a full
      illustration. We demonstrate here that engineered protein fragments, although
      being non-functional in solution, can be re-assembled within the nanometer space
      to give the full activity of the whole protein. Specific interaction between
      hexahistidine-tag (His-tag) and NiO surface immobilizes protein fragments on NiO
      nanoparticles to form a self-assembled protein "corona" on the particles inside
      the nanopores of mesoporous silica. Site-specific assembly forces a shoulder-by
      shoulder orientation and promotes fragment-fragment interaction; this interaction
      together with spatial confinement of the mesopores results in functional re
      assembly of the protein half fragments. To our surprise, a single half fragment
      of luciferase (non-catalytic in solution) exhibited luciferase activity when
      immobilized on NiO in the mesopores, in the absence of the complimentary half.
      This shows for the first time that spatial confinement can induce the folding of
      a half fragment, reconstitute the enzyme active site, and re-gain the catalytic
      capability of the whole protein. Our work thereby highlights the under-documented
      notion that aside from the chemical composition such as primary sequence,
      physical environment of a protein also determines its function. 

PMID- 25875004
TI  - Growth and development in Chinese pre-schoolers with picky eating behaviour: a
      cross-sectional study.
AB  - OBJECTIVE: To explore the associations between picky eating behaviour and pre
      schoolers' growth and development. Corresponding potential mechanisms, such as
      nutrient and food subgroup intake, as well as micronutrients in the blood, will
      be considered. METHODS: Picky eating behaviour was present if it was reported by
      parents. From various areas of China, 937 healthy children of 3-7 years old were
      recruited using a multi-stage stratified cluster sampling method. Children and
      their mothers' socio-demographic information and children's anthropometry,
      intelligence, blood samples, one 24-hour dietary intake record and food frequency
      questionnaire were collected. Z-scores and intelligence tests were used to
      evaluate growth and development (cognitive development). Multilevel models were
      employed to verify the associations between picky eating behaviour and growth and
      development. RESULTS: The prevalence of picky eating as reported by parents was
      54% in pre-schoolers. Compared with the non-picky eaters, weight for age in picky
      eaters was 0.14 z-score (95% CI: -0.25, -0.02; p = 0.017) lower while no
      significant difference was found in intelligence (p > 0.05). Picky eating
      behaviour lasting over two years was associated with lower weight for age, as was
      nit-picking meat (the prevalence from parents' perception was 23% in picky
      eaters) (p < 0.05). Picky eaters consumed fewer cereals, vegetables, and fish (p
      < 0.05), and had a lower dietary intake of protein, dietary fibre, iron, and zinc
      (p < 0.05). There were no differences in the concentrations of essential minerals
      in whole blood (p > 0.05). CONCLUSIONS: Picky eating behaviour is reported by
      parents in half of the Chinese pre-schoolers, which is negatively associated with
      growth (weight for age). Lower protein and dietary fibre as well as lower iron
      and zinc intakes were associated with picky eating as were lower intakes of
      vegetables, fish and cereals.

PMID- 25875005
TI  - Iohexol clearance for determination of glomerular filtration rate in rats induced
      to acute renal failure.
AB  - INTRODUCTION: The glomerular filtration rate (GFR) is considered an especially
      important tool for the measurement of renal function. Inulin clearance (InCl) is
      the classic reference method for this purpose, although it is associated with a
      number of disadvantages; thus, other markers have been proposed, including
      iohexol. Determination of iohexol clearance (IoCl) has been established for
      clinical use; however, its application as a GFR marker in experimental rat models
      has not been reported. OBJECTIVES: This study aims to standardize a methodology
      for the measurement of iohexol clearance and to evaluate its applicability as a
      marker of GFR in rats with induced toxic acute renal failure (ARF), using InCl as
      the gold standard. MATERIALS AND METHODS: Twenty-six Wistar male rats (200-300 g)
      were divided into the following two groups: a control group (n=7) and an ARF
      group (n=19). ARF was induced by the subcutaneous administration of cisplatin (5
      mg/kg); IoCl and InCl were determined simultaneously, and plasma creatinine
      (pCreat) dosage was measured colorimetrically. RESULTS: The pCreat, InCl and IoCl
      levels were consistent with the expected values for the renal function ranges of
      the evaluated animals, and the IoCl and InCl levels were significantly correlated
      (r=0.792). An inverse moderate linear correlation between the IoCl and pCreat
      measurements (r=-0.587) and between the InCl and pCreat measurements (r=-0.722)
      were observed. CONCLUSION: These results confirm a correlation between IoCl and
      the gold standard of GFR, InCl measurement. IoCl offers a relevant advantage over
      InCl because determination of the former allows the animal to live after the
      procedure.

PMID- 25875006
TI  - Distribution of uranium, thorium and some stable trace and toxic elements in
      human hair and nails in Niska Banja Town, a high natural background radiation
      area of Serbia (Balkan Region, South-East Europe).
AB  - Human hair and nails can be considered as bio-indicators of the public exposure
      to certain natural radionuclides and other toxic metals over a long period of
      months or even years. The level of elements in hair and nails usually reflect
      their levels in other tissues of body. Niska Banja, a spa town located in
      southern Serbia, with locally high natural background radiation was selected for
      the study. To assess public exposure to the trace elements, hair and nail samples
      were collected and analyzed. The concentrations of uranium, thorium and some
      trace and toxic elements (Mn, Ni, Cu, Sr, Cd, and Cs) were determined using
      inductively coupled plasma mass spectrometry (ICP-MS). U and Th concentrations in
      hair varied from 0.0002 to 0.0771 MUg/g and from 0.0002 to 0.0276 MUg/g,
      respectively. The concentrations in nails varied from 0.0025 to 0.0447 MUg/g and
      from 0.0023 to 0.0564 MUg/g for U and Th, respectively. We found significant
      correlations between some elements in hair and nails. Also indications of spatial
      clustering of high values could be found. However, this phenomenon as well as the
      large variations in concentrations of heavy metals in hair and nail could not be
      explained. As hypotheses, we propose possible exposure pathways which may explain
      the findings, but the current data does not allow testing them. 

PMID- 25875007
TI  - Dating of sediments from four Swiss prealpine lakes with (210)Pb determined by
      gamma-spectrometry: progress and problems.
AB  - In this paper the most important problems in dating lake sediments with
      unsupported (210)Pb are summarized and the progress in gamma-spectrometry of the
      unsupported (210)Pb is discussed. The main topics of these studies concern
      sediment samples preparation for gamma-spectrometry, measurement techniques and
      data analysis, as well as understanding of accumulation and sedimentation
      processes in lakes. The vertical distributions of artificial ((137)Cs, (241)Am,
      (239)Pu) and natural radionuclides ((40)K, (210,214)Pb, (214)Bi) as well as
      stable trace elements (Fe, Mn, Pb) in sediment cores from four Swiss lakes were
      used as examples for the interpretation, inter-comparison and validation of depth
      age relations established by three (210)Pb-based models (CF-CSR, CRS and SIT).
      The identification of turbidite layers and the influence of the turbidity flows
      on the accuracy of sediment dating is demonstrated. Time-dependent mass
      sedimentation rates in lakes Brienz, Thun, Biel and Lucerne are discussed and
      compared with published data. 

PMID- 25875008
TI  - OCAM regulates embryonic spinal cord stem cell proliferation by modulating ErbB2
      receptor.
AB  - The proliferation and differentiation of neural stem cells are tightly controlled
      by intrinsic and extrinsic cues. Cell adhesion molecules are increasingly
      recognized as regulators of these processes. Here we report the expression of the
      olfactory cell adhesion molecule (OCAM/NCAM2/RNCAM) during mouse spinal cord
      development and in neural stem cells cultured as neurospheres. OCAM is also
      weakly expressed in the dormant adult stem cell niche around the central canal
      and is overexpressed after spinal cord injury. Both transmembrane (TM) and
      glycosylphosphatidylinositol (GPI)-linked isoforms are present in neurospheres.
      Electron microscopy and internalisation experiments revealed a dynamic
      trafficking of OCAM between the membrane and intracellular compartments. After
      differentiation, OCAM remains in neurons and oligodendrocytes whereas no
      expression is detected in astrocytes. Using OCAM knockout (KO) mice, we found
      that mutant spinal cord stem cells showed an increased proliferation and self
      renewal rates although no effect on differentiation was observed. This effect was
      reversed by lentivirus-mediated re-introduction of OCAM. Mechanistically, we
      identified the ErbB2/Neu/HER2 protein as being implicated in the enhanced
      proliferation of mutant cells. ErbB2 protein expression and phosphorylation level
      were significantly increased in KO cells whereas no difference was observed at
      the mRNA level. Overexpression of ErbB2 in wild-type and mutant cells also
      increased their growth while reintroduction of OCAM in mutant cells reduced the
      level of phosphorylated ErbB2. These results indicate that OCAM exerts a
      posttranscriptional control on the ErbB2 signalling in spinal cord stem cells.
      This study adds further support for considering cell adhesion molecules as
      regulators of the ErbB signalling. 

PMID- 25875009
TI  - Fusion of the genes EWSR1 and PBX3 in retroperitoneal leiomyoma with
      t(9;22)(q33;q12).
AB  - Retroperitoneal leiomyoma is a rare benign smooth muscle tumor almost exclusively
      found in women and with histopathological features similar to uterine leiomyomas.
      The pathogenesis of retroperitoneal leiomyoma is unclear and next to nothing is
      known about the cytogenetics and molecular genetics of the tumor. We present here
      a retroperitoneal leiomyoma with a t(9;22)(q33;q12) as the sole karyotypic
      aberration. The translocation resulted in an EWSR1-PBX3 fusion gene in which exon
      9 of EWSR1 (nucleotide 1320 accession number NM_013986 version 3) was in-frame
      fused to exon 5 of PBX3 (nucleotide 824 accession number NM_006195 version 5).
      The EWSR1-PBX3 fusion transcript codes for a 529 amino acids long chimeric EWSR1
      PBX3 protein which contains the N-terminal transactivation part of EWSR1 and the
      homeodomain of PBX3. The present study, together with our previous finding of a
      retroperitoneal leiomyoma with t(10;17)(q22;q21) as the sole karyotypic
      aberration and a KAT6B-KANSL1 fusion gene, indicates that retroperitoneal
      leiomyomas may be characterized by fusion genes coding for chimeric proteins.
      However, cytogenetic and molecular heterogeneity exists in these tumors and it is
      too early to tell how many and which different pathways lead to retroperitoneal
      leiomyomagenesis. 

PMID- 25875010
TI  - Monitoring Sub-Saharan African physician migration and recruitment post-adoption
      of the WHO code of practice: temporal and geographic patterns in the United
      States.
AB  - Data monitoring is a key recommendation of the WHO Global Code of Practice on the
      International Recruitment of Health Personnel, a global framework adopted in May
      2010 to address health workforce retention in resource-limited countries and the
      ethics of international migration. Using data on African-born and African
      educated physicians in the 2013 American Medical Association Physician Masterfile
      (AMA Masterfile), we monitored Sub-Saharan African (SSA) physician recruitment
      into the physician workforce of the United States (US) post-adoption of the WHO
      Code of Practice. From the observed data, we projected to 2015 with linear
      regression, and we mapped migrant physicians' locations using GPS Visualizer and
      ArcGIS. The 2013 AMA Masterfile identified 11,787 active SSA-origin physicians,
      representing barely 1.3% (11,787/940,456) of the 2013 US physician workforce, but
      exceeding the total number of physicians reported by WHO in 34 SSA countries (N =
      11,519). We estimated that 15.7% (1,849/11,787) entered the US physician
      workforce after the Code of Practice was adopted. Compared to pre-Code estimates
      from 2002 (N = 7,830) and 2010 (N = 9,938), the annual admission rate of SSA
      emigres into the US physician workforce is increasing. This increase is due in
      large part to the growing number of SSA-born physicians attending medical schools
      outside SSA, representing a trend towards younger migrants. Projection estimates
      suggest that there will be 12,846 SSA migrant physicians in the US physician
      workforce in 2015, and over 2,900 of them will be post-Code recruits. Most SSA
      migrant physicians are locating to large urban US areas where physician densities
      are already the highest. The Code of Practice has not slowed the SSA-to-US
      physician migration. To stem the physician "brain drain", it is essential to
      incentivize professional practice in SSA and diminish the appeal of US migration
      with bolder interventions targeting primarily early-career (age <= 35) SSA
      physicians. 

PMID- 25875011
TI  - Does visceral osteopathic treatment accelerate meconium passage in very low birth
      weight infants?- A prospective randomized controlled trial.
AB  - BACKGROUND: To determine whether the complementary approach of visceral
      manipulative osteopathic treatment accelerates complete meconium excretion and
      improves feeding tolerance in very low birth weight infants. METHODS: This study
      was a prospective, randomized, controlled trial in premature infants with a birth
      weight <1500 g and a gestational age <32 weeks who received a visceral
      osteopathic treatment 3 times during their first week of life or no treatment.
      RESULTS: Passage of the last meconium occurred after a median of 7.5 days (95%
      confidence interval: 6-9 days, n = 21) in the intervention group and after 6 days
      (95% confidence interval: 5-9 days, n = 20,) in the control group (p = 0.11).
      However, osteopathic treatment was associated with a 8 day longer time to full
      enteral feedings (p = 0.02), and a 34 day longer hospital stay (Median = 66 vs.
      100 days i.e.; p=0.14). Osteopathic treatment was tolerated well and no adverse
      events were observed. CONCLUSIONS: Visceral osteopathic treatment of the abdomen
      did not accelerate meconium excretion in VLBW (very low birth weight)-infants.
      However infants in the osteopathic group had a longer time to full enteral
      feedings and a longer hospital stay, which could represent adverse effects. Based
      on our trial results, we cannot recommend visceral osteopathic techniques in VLBW
      infants. TRIAL REGISTRATION: Clinical trials.gov: NCT02140710.

PMID- 25875012
TI  - Risk factors and birth outcomes of anaemia in early pregnancy in a nulliparous
      cohort.
AB  - BACKGROUND: Anaemia in pregnancy is a major public health and economic problem
      worldwide, that contributes to both maternal and fetal morbidity and mortality.
      OBJECTIVE: The aim of the study was to calculate the prevalence of anaemia in
      early pregnancy in a cohort of 'low risk' women participating in a large
      international multicentre prospective study (n = 5 609), to identify the
      modifiable risk factors for anaemia in pregnancy in this cohort, and to compare
      the birth outcomes between pregnancies with and without anaemia in early
      gestation. METHODS: The study is an analysis of data that were collected
      prospectively during the Screening for Pregnancy Endpoints study. Anaemia was
      defined according to the World Health Organization's definition of anaemia in
      pregnancy (haemoglobin < 11g/dL). Binary logistic regression with adjustment for
      potential confounders (country, maternal age, having a marital partner, ethnic
      origin, years of schooling, and having paid work) was the main method of
      analysis. RESULTS: The hallmark findings were the low prevalence of anaemia
      (2.2%), that having no marital partner was an independent risk factor for having
      anaemia (OR 1.34, 95% CI 1.01-1.78), and that there was no statistically
      significant effect of anaemia on adverse pregnancy outcomes (small for
      gestational age, pre-tem birth, mode of delivery, low birth weight, APGAR score <
      7 at one and five minutes). Adverse pregnancy outcomes were however more common
      in those with anaemia than in those without. CONCLUSION: In this low risk healthy
      pregnant population we found a low anaemia rate. The absence of a marital partner
      was a non-modifiable factor, albeit one which may reflect a variety of
      confounding factors, that should be considered for addition to anaemia's
      conceptual framework of determinants. Although not statistically significant,
      clinically, a trend towards a higher risk of adverse pregnancy outcomes was
      observed in women that were anaemic in early pregnancy.

PMID- 25875013
TI  - Brain responses to emotional salience and reward in alcohol use disorder.
AB  - Heightened neural responsiveness of alcoholics to alcohol cues and social emotion
      may impede sobriety. To test mesocorticolimbic network responsivity, 10 (8 men)
      alcohol use disorder (AUD) patients sober for 3 weeks to 10 months and 11 (8 men)
      controls underwent fMRI whilst viewing pictures of alcohol and non-alcohol
      beverages and of emotional faces (happy, sad, angry). AUD and controls showed
      similarities in mesocorticolimbic activity: both groups activated fusiform for
      emotional faces and hippocampal and pallidum regions during alcohol picture
      processing. In AUD, less fusiform activity to emotional faces and more pallidum
      activity to alcohol pictures were associated with longer sobriety. Using graph
      theory-based network efficiency measures to specify the role of the
      mesocorticolimbic network nodes for emotion and reward in sober AUD revealed that
      the left hippocampus was less efficiently connected with the other task-activated
      network regions in AUD than controls when viewing emotional faces, while the
      pallidum was more efficiently connected when viewing alcohol beverages. Together
      our findings identified lower occipito-temporal sensitivity to emotional faces
      and enhanced striatal sensitivity to alcohol stimuli in AUD than controls.
      Considering the role of the striatum in encoding reward, its activation
      enhancement with longer sobriety may reflect adaptive neural changes in the first
      year of drinking cessation and mesocorticolimbic system vulnerability for
      encoding emotional salience and reward potentially affecting executive control
      ability and relapse propensity during abstinence.

PMID- 25875014
TI  - The suppression of brain activation in post-deployment military personnel with
      posttraumatic stress symptoms.
AB  - Previous research using cognitive paradigms has found task-related activation
      that includes prefrontal brain structures and that is attenuated in association
      with posttraumatic stress symptoms (PTSS). The present investigation used a
      cognitive control paradigm, the Arrows Task, to study subjects who had not
      sustained a traumatic brain injury during deployment and who had a wide range of
      scores on the Posttraumatic Stress Disorder Checklist (PCL). During the Arrows
      Task there was no significant activation within the full sample of 15 subjects,
      but deactivation was found within areas that are likely to be involved in
      cognitive control, including the dorsal anterior cingulate gyrus and parietal
      cortex. Exploratory analyses were also conducted to compare subjects with
      relatively high PTSS (HIGH PTSS, n = 7) to those with lower severity or no
      symptoms (LOW PTSS, n = 8). LOW PTSS subjects exhibited activation in nonfrontal
      brain areas and their activation was greater relative to the HIGH PTSS subjects.
      In contrast, the HIGH PTSS group had extensive deactivation and there was a
      negative relationship between activation and PCL scores within subcortical
      structures, the cerebellum, and higher-order cortical association areas. For the
      HIGH PTSS group there was also a positive relationship between PCL scores and
      activation within basic sensory and motor areas, as well as structures thought to
      have a role in emotion and the regulation of internal bodily states. These
      findings are consistent with widespread neural dysfunction in subjects with
      greater PTSS, including changes similar to those reported to occur with acute
      stress and elevated noradrenergic activity. 

PMID- 25875015
TI  - Quercetin represses apolipoprotein B expression by inhibiting the transcriptional
      activity of C/EBPbeta.
AB  - Quercetin is one of the most abundant polyphenolic flavonoids found in fruits and
      vegetables and has anti-oxidative and anti-obesity effects. Because the small
      intestine is a major absorptive organ of dietary nutrients, it is likely that
      highly concentrated food constituents, including polyphenols, are present in the
      small intestinal epithelial cells, suggesting that food factors may have a
      profound effect in this tissue. To identify novel targets of quercetin in the
      intestinal enterocytes, mRNA profiling using human intestinal epithelial Caco-2
      cells was performed. We found that mRNA levels of some apolipoproteins,
      particularly apolipoprotein B (apoB), are downregulated in the presence of
      quercetin. On the exposure of Caco-2 cells to quercetin, both mRNA and protein
      levels of apoB were decreased. Promoter analysis of the human apoB revealed that
      quercetin response element is localized at the 5'-proximal promoter region, which
      contains a conserved CCAAT enhancer-binding protein (C/EBP)-response element. We
      found that quercetin reduces the promoter activity of apoB, driven by the
      enforced expression of C/EBPbeta. Quercetin had no effect on either mRNA or
      protein levels of C/EBPbeta. In contrast, we found that quercetin inhibits the
      transcriptional activity of C/EBPbeta but not its recruitment to the apoB
      promoter. On the exposure of Caco-2 cells to quercetin 3-O-glucuronide, which is
      in a cell-impermeable form, no notable change in apoB mRNA was observed,
      suggesting an intracellular action of quercetin. In vitro interaction experiments
      using quercetin-conjugated beads revealed that quercetin binds to C/EBPbeta. Our
      results describe a novel regulatory mechanism of transcription of apolipoprotein
      genes by quercetin in the intestinal enterocytes. 

PMID- 25875016
TI  - Nanocomposite treatment reduces disease and lethality in a murine model of acute
      graft-versus-host disease and preserves anti-tumor effects.
AB  - Graft versus host disease (GVHD) is an immunological disorder triggered by bone
      marrow transplantation that affects several organs, including the
      gastrointestinal tract and liver. Fullerenes and their soluble forms, fullerols,
      are nanocomposites with a closed symmetrical structure with anti-inflammatory and
      anti-oxidant properties. The present study evaluated the effects of treatment
      with the fullerol (C60(OH)18-20) in the development and pathogenesis of GVHD in a
      murine model. Mice with experimental GVHD that were treated with the fullerol
      showed reduced clinical signs of disease and mortality compared with untreated
      mice. Treatment with the fullerol decreased the hepatic damage associated with
      reduced hepatic levels of reactive oxygen species, pro-inflammatory cytokines and
      chemokines (IFN-gamma TNF-alpha, CCL2, CCL3 and CCL5) and reduced leukocyte
      accumulation. The amelioration of GVHD after treatment with the fullerol was also
      associated with reduced intestinal lesions and consequent bacterial translocation
      to the blood, liver and peritoneal cavity. Moreover, the fullerol treatment
      alleviated the GVHD while preserving effects of the graft against a leukemia cell
      line (GFP+P815). In summary, the fullerol was effective in reducing the GVHD
      inflammatory response in mice and may suggest novel ways to treat this disease. 

PMID- 25875017
TI  - Neofunctionalization of the Sec1 alpha1,2fucosyltransferase paralogue in leporids
      contributes to glycan polymorphism and resistance to rabbit hemorrhagic disease
      virus.
AB  - RHDV (rabbit hemorrhagic disease virus), a virulent calicivirus, causes high
      mortalities in European rabbit populations (Oryctolagus cuniculus). It uses
      alpha1,2fucosylated glycans, histo-blood group antigens (HBGAs), as attachment
      factors, with their absence or low expression generating resistance to the
      disease. Synthesis of these glycans requires an alpha1,2fucosyltransferase. In
      mammals, there are three closely located alpha1,2fucosyltransferase genes rSec1,
      rFut2 and rFut1 that arose through two rounds of duplications. In most mammalian
      species, Sec1 has clearly become a pseudogene. Yet, in leporids, it does not
      suffer gross alterations, although we previously observed that rabbit Sec1
      variants present either low or no activity. Still, a low activity rSec1 allele
      correlated with survival to an RHDV outbreak. We now confirm the association
      between the alpha1,2fucosyltransferase loci and survival. In addition, we show
      that rabbits express homogenous rFut1 and rFut2 levels in the small intestine.
      Comparison of rFut1 and rFut2 activity showed that type 2 A, B and H antigens
      recognized by RHDV strains were mainly synthesized by rFut1, and all rFut1
      variants detected in wild animals were equally active. Interestingly, rSec1 RNA
      levels were highly variable between individuals and high expression was
      associated with low binding of RHDV strains to the mucosa. Co-transfection of
      rFut1 and rSec1 caused a decrease in rFut1-generated RHDV binding sites,
      indicating that in rabbits, the catalytically inactive rSec1 protein acts as a
      dominant-negative of rFut1. Consistent with neofunctionalization of Sec1 in
      leporids, gene conversion analysis showed extensive homogenization between Sec1
      and Fut2 in leporids, at variance with its limited degree in other mammals. Gene
      conversion additionally involving Fut1 was also observed at the C-terminus. Thus,
      in leporids, unlike in most other mammals where it became extinct, Sec1 evolved a
      new function with a dominant-negative effect on rFut1, contributing to
      fucosylated glycan diversity, and allowing herd protection from pathogens such as
      RHDV. 

PMID- 25875019
TI  - A stochastic simulation framework for the prediction of strategic noise mapping
      and occupational noise exposure using the random walk approach.
AB  - Strategic noise mapping provides important information for noise impact
      assessment and noise abatement. However, producing reliable strategic noise
      mapping in a dynamic, complex working environment is difficult. This study
      proposes the implementation of the random walk approach as a new stochastic
      technique to simulate noise mapping and to predict the noise exposure level in a
      workplace. A stochastic simulation framework and software, namely RW-eNMS, were
      developed to facilitate the random walk approach in noise mapping prediction.
      This framework considers the randomness and complexity of machinery operation and
      noise emission levels. Also, it assesses the impact of noise on the workers and
      the surrounding environment. For data validation, three case studies were
      conducted to check the accuracy of the prediction data and to determine the
      efficiency and effectiveness of this approach. The results showed high accuracy
      of prediction results together with a majority of absolute differences of less
      than 2 dBA; also, the predicted noise doses were mostly in the range of
      measurement. Therefore, the random walk approach was effective in dealing with
      environmental noises. It could predict strategic noise mapping to facilitate
      noise monitoring and noise control in the workplaces. 

PMID- 25875018
TI  - Biochemical, transcriptomic and proteomic analyses of digestion in the scorpion
      Tityus serrulatus: insights into function and evolution of digestion in an
      ancient arthropod.
AB  - Scorpions are among the oldest terrestrial arthropods and they have passed
      through small morphological changes during their evolutionary history on land.
      They are efficient predators capable of capturing and consuming large preys and
      due to envenomation these animals can become a human health challenge.
      Understanding the physiology of scorpions can not only lead to evolutionary
      insights but also is a crucial step in the development of control strategies.
      However, the digestive process in scorpions has been scarcely studied. In this
      work, we describe the combinatory use of next generation sequencing, proteomic
      analysis and biochemical assays in order to investigate the digestive process in
      the yellow scorpion Tityus serrulatus, mainly focusing in the initial protein
      digestion. The transcriptome generated database allowed the quantitative
      identification by mass spectrometry of different enzymes and proteins involved in
      digestion. All the results suggested that cysteine cathepsins play an important
      role in protein digestion. Two digestive cysteine cathepsins were isolated and
      characterized presenting acidic characteristics (pH optima and stability),
      zymogen conversion to the mature form after acidic activation and a cross-class
      inhibition by pepstatin. A more elucidative picture of the molecular mechanism of
      digestion in a scorpion was proposed based on our results from Tityus serrulatus.
      The midgut and midgut glands (MMG) are composed by secretory and digestive cells.
      In fasting animals, the secretory granules are ready for the next predation
      event, containing enzymes needed for alkaline extra-oral digestion which will
      compose the digestive fluid, such as trypsins, astacins and chitinase. The
      digestive vacuoles are filled with an acidic proteolytic cocktail to the
      intracellular digestion composed by cathepsins L, B, F, D and legumain. Other
      proteins as lipases, carbohydrases, ctenitoxins and a chitolectin with a
      perithrophin domain were also detected. Evolutionarily, a large gene duplication
      of cathepsin L occurred in Arachnida with the sequences from ticks being
      completely divergent from other arachnids probably due to the particular
      selective pressures over this group. 

PMID- 25875020
TI  - Functionality of dengue virus specific memory T cell responses in individuals who
      were hospitalized or who had mild or subclinical dengue infection.
AB  - BACKGROUND: Although antibody responses to dengue virus (DENV) in naturally
      infected individuals have been extensively studied, the functionality of DENV
      specific memory T cell responses in relation to clinical disease severity is
      incompletely understood. METHODOLOGY/PRINCIPAL FINDINGS: Using ex vivo IFNgamma
      ELISpot assays, and by determining cytokines produced in ELISpot supernatants, we
      investigated the functionality of DENV-specific memory T cell responses in a
      large cohort of individuals from Sri Lanka (n=338), who were naturally infected
      and were either hospitalized due to dengue or had mild or sub clinical dengue
      infection. We found that T cells of individuals with both past mild or sub
      clinical dengue infection and who were hospitalized produced multiple cytokines
      when stimulated with DENV-NS3 peptides. However, while DENV-NS3 specific T cells
      of those with mild/sub clinical dengue infection were more likely to produce only
      granzyme B (p=0.02), those who were hospitalized were more likely to produce both
      TNFalpha and IFNgamma (p=0.03) or TNFalpha alone. We have also investigated the
      usefulness of a novel T cell based assay, which can be used to determine the past
      infecting DENV serotype. 92.4% of DENV seropositive individuals responded to at
      least one DENV serotype of this assay and none of the seronegatives responded.
      Individuals who were seronegative, but had received the Japanese encephalitis
      vaccine too made no responses, suggesting that the peptides used in this assay
      did not cross react with the Japanese encephalitis virus.
      CONCLUSIONS/SIGNIFICANCE: The types of cytokines produced by DENV-specific memory
      T cells appear to influence the outcome of clinical disease severity. The novel T
      cell based assay, is likely to be useful in determining the past infecting DENV
      serotype in immune-epidemiological studies and also in dengue vaccine trials.

PMID- 25875021
TI  - A realist review of brief interventions for alcohol misuse delivered in emergency
      departments.
AB  - BACKGROUND: Brief interventions (BIs) involve screening for alcohol misuse and
      providing feedback to patients about their use, with the aim of reducing alcohol
      consumption and related consequences. BIs have been implemented in various
      healthcare settings, including emergency departments (ED), where they have been
      found to contribute mixed results in their ability to address alcohol misuse
      among adults. Mechanisms through which BIs work and contextual factors impacting
      BI effectiveness are not clear. The purpose of this review was to understand how,
      for whom, and under what circumstances BIs work for adults misusing alcohol and
      who have been admitted to an ED. A realist review was chosen to answer these
      questions as realist reviews create context-mechanism-outcome configurations,
      leading to the development of comprehensive and detailed theories; in this case
      explaining how and for whom BIs work. METHODS: Databases including PsycINFO,
      Healthstar, CINAHL, Medline, and Nursing and Allied Health were searched for
      articles published until December 2013. The search strategy focused on studies
      examining BIs that targeted alcohol misuse among adults admitted into the ED. The
      search identified 145 relevant abstracts, of which 36 were included in the
      review. The literature was synthesized qualitatively (immersion/crystallization).
      RESULTS: Four mechanisms were found within reviewed studies, including engagement
      in/retention of BI materials, resolving ambivalence, increased awareness/insight
      into consequences of drinking, and increased self-efficacy/empowerment to use
      skills for change. The following contexts were found to impact mechanisms:
      emotional state, injury attributed to alcohol use, severity of alcohol use, and
      baseline stage of change. CONCLUSIONS: This realist review provides advances in
      theories regarding which mechanisms to target during a BI and which contexts
      create the most favorable conditions for these mechanisms to occur, ultimately
      leading to optimal BI outcomes. These results can inform future clinical decision
      making when delivering BIs in ED settings. Future research should conduct
      quantitative examination to confirm these findings. SYSTEMATIC REVIEW
      REGISTRATION: PROSPERO CRD42013006549.

PMID- 25875022
TI  - Fibrinolysis and proliferative endarteritis: two related processes in chronic
      infections? The model of the blood-borne pathogen Dirofilaria immitis.
AB  - The interaction between blood-borne pathogens and fibrinolysis is one of the most
      important mechanisms that mediate invasion and the establishment of infectious
      agents in their hosts. However, overproduction of plasmin (final product of the
      route) has been related in other contexts to proliferation and migration of the
      arterial wall cells and degradation of the extracellular matrix. We have recently
      identified fibrinolysis-activating antigens from Dirofilaria immitis, a blood
      borne parasite whose key pathological event (proliferative endarteritis) is
      produced by similar mechanisms to those indicated above. The objective of this
      work is to study how two of this antigens [actin (ACT) and fructose-bisphosphate
      aldolase (FBAL)] highly conserved in pathogens, activate fibrinolysis and to
      establish a relationship between this activation and the development of
      proliferative endarteritis during cardiopulmonary dirofilariasis. We demonstrate
      that both proteins bind plasminogen, enhance plasmin generation, stimulate the
      expression of the fibrinolytic activators tPA and uPA in endothelial cell
      cultures and are located on the surface of the worm in contact with the host's
      blood. ELISA, western blot and immunofluorescence techniques were employed for
      this purpose. Additionally, the implication of lysine residues in this
      interaction was analyzed by bioinformatics. The involvement of plasmin generated
      by the ACT/FBAL and plasminogen binding in cell proliferation and migration, and
      degradation of the extracellular matrix were shown in an "in vitro" model of
      endothelial and smooth muscle cells in culture. The obtained results indicate
      that ACT and FBAL from D. immitis activate fibrinolysis, which could be used by
      the parasite like a survival mechanism to avoid the clot formation. However, long
      term overproduction of plasmin can trigger pathological events similar to those
      described in the emergence of proliferative endarteritis. Due to the high degree
      of evolutionary conservation of these antigens, similar processes may occur in
      other blood-borne pathogens. 

PMID- 25875023
TI  - Altered metabolic and stemness capacity of adipose tissue-derived stem cells from
      obese mouse and human.
AB  - Adipose stem cells (ASCs) are an appealing source of cells for therapeutic
      intervention; however, the environment from which ASCs are isolated may impact
      their usefulness. Using a range of functional assays, we have evaluated whether
      ASCs isolated from an obese environment are comparable to cells from non-obese
      adipose tissue. Results showed that ASCs isolated from obese tissue have a
      reduced proliferative ability and a loss of viability together with changes in
      telomerase activity and DNA telomere length, suggesting a decreased self-renewal
      capacity. Metabolic analysis demonstrated that mitochondrial content and function
      was impaired in obese-derived ASCs resulting in changes in favored oxidative
      substrates. These findings highlight the impact of obesity on adult stem
      properties. Hence, caution should be exercised when considering the source of
      ASCs for cellular therapies since their therapeutic potential may be impaired. 

PMID- 25875025
TI  - Effect of sour tea (Hibiscus sabdariffa L.) on arterial hypertension: a
      systematic review and meta-analysis of randomized controlled trials.
AB  - BACKGROUND: Hibiscus sabdariffa L. is a tropical wild plant rich in organic
      acids, polyphenols, anthocyanins, polysaccharides, and volatile constituents that
      are beneficial for the cardiovascular system. Hibiscus sabdariffa beverages are
      commonly consumed to treat arterial hypertension, yet the evidence from
      randomized controlled trials (RCTs) has not been fully conclusive. Therefore, we
      aimed to assess the potential antihypertensive effects of H. sabdariffa through
      systematic review of literature and meta-analysis of available RCTs. METHODS: The
      search included PUBMED, Cochrane Library, Scopus, and EMBASE (up to July 2014) to
      identify RCTs investigating the efficacy of H. sabdariffa supplementation on SBP
      and DBP values. Two independent reviewers extracted data on the study
      characteristics, methods, and outcomes. Quantitative data synthesis and meta
      regression were performed using a fixed-effect model, and sensitivity analysis
      using leave-one-out method. Five RCTs (comprising seven treatment arms) were
      selected for the meta-analysis. In total, 390 participants were randomized, of
      whom 225 were allocated to the H. sabdariffa supplementation group and 165 to the
      control group in the selected studies. RESULTS: Fixed-effect meta-regression
      indicated a significant effect of H. sabdariffa supplementation in lowering both
      SBP (weighed mean difference -7.58 mmHg, 95% confidence interval -9.69 to -5.46,
      P < 0.00001) and DBP (weighed mean difference -3.53 mmHg, 95% confidence interval
      -5.16 to -1.89, P < 0.0001). These effects were inversely associated with
      baseline BP values, and were robust in sensitivity analyses. CONCLUSION: This
      meta-analysis of RCTs showed a significant effect of H. sabdariffa in lowering
      both SBP and DBP. Further well designed trials are necessary to validate these
      results.

PMID- 25875024
TI  - Attenuation of high-frequency (50-200 Hz) thalamocortical EEG rhythms by propofol
      in rats is more pronounced for the thalamus than for the cortex.
AB  - BACKGROUND: Thalamocortical EEG rhythms in gamma (30-80 Hz) and high-gamma (80
      200 Hz) ranges have been linked to arousal and conscious processes. To test the
      hypothesis that general anesthetics attenuate these rhythms, we characterized the
      concentration-effect relationship of propofol on the spectral power of these
      rhythms. In view of the ongoing debate about cortex versus thalamus as the
      primary site of anesthetic action for unconsciousness, we also compared the
      relative sensitivity of cortex and thalamus to this effect propofol. METHODS:
      Adult male Long-Evans rats were chronically implanted with electrodes in
      somatosensory (barrel) cortex and ventroposteromedial thalamus. Propofol was
      delivered by a computer-controlled infusion using real-time pharmacokinetic
      modeling to obtain the desired plasma concentration. Spectral power was assessed
      during baseline, at four stable propofol plasma-concentrations (0, 3,6,9,12
      MUg/ml) and during recovery over four frequency ranges (30-50, 51-75, 76-125, 126
      200 Hz). Unconsciousness was defined as complete loss of righting reflex.
      Multiple regression was used to model the change of power (after logarithmic
      transformation) as a function of propofol concentration and recording site.
      RESULTS: Unconsciousness occurred at the 9 MUg/ml concentration in all animals.
      Propofol caused a robust linear concentration-dependent attenuation of cortical
      power in the 76-200 Hz range and of thalamic power in the 30-200 Hz range. In all
      instances the concentration-effect slope for the thalamus was markedly steeper
      than for the cortex. Furthermore the lowest concentration causing unconsciousness
      significantly reduced cortical power in the 126-200 Hz range and thalamic power
      in the 30-200 Hz range. CONCLUSIONS: Propofol causes a concentration-dependent
      attenuation of the power of thalamocortical rhythms in the 30-200 Hz range and
      this effect is far more pronounced for the thalamus, where the attenuation
      provides a robust correlate of the hypnotic action of propofol [corrected].

PMID- 25875026
TI  - Crickets are not a free lunch: protein capture from scalable organic side-streams
      via high-density populations of Acheta domesticus.
AB  - It has been suggested that the ecological impact of crickets as a source of
      dietary protein is less than conventional forms of livestock due to their
      comparatively efficient feed conversion and ability to consume organic side
      streams. This study measured the biomass output and feed conversion ratios of
      house crickets (Acheta domesticus) reared on diets that varied in quality,
      ranging from grain-based to highly cellulosic diets. The measurements were made
      at a much greater population scale and density than any previously reported in
      the scientific literature. The biomass accumulation was strongly influenced by
      the quality of the diet (p<0.001), with the nitrogen (N) content, the ratio of N
      to acid detergent fiber (ADF) content, and the crude fat (CF) content
      (y=N/ADF+CF) explaining most of the variability between feed treatments (p =
      0.02; R2 = 0.96). In addition, for populations of crickets that were able to
      survive to a harvestable size, the feed conversion ratios measured were higher
      (less efficient) than those reported from studies conducted at smaller scales and
      lower population densities. Compared to the industrial-scale production of
      chickens, crickets fed a poultry feed diet showed little improvement in protein
      conversion efficiency, a key metric in determining the ecological footprint of
      grain-based livestock protein. Crickets fed the solid filtrate from food waste
      processed at an industrial scale via enzymatic digestion were able to reach a
      harvestable size and achieve feed and protein efficiencies similar to that of
      chickens. However, crickets fed minimally-processed, municipal-scale food waste
      and diets composed largely of straw experienced >99% mortality without reaching a
      harvestable size. Therefore, the potential for A. domesticus to sustainably
      supplement the global protein supply, beyond what is currently produced via grain
      fed chickens, will depend on capturing regionally scalable organic side-streams
      of relatively high-quality that are not currently being used for livestock
      production. 

PMID- 25875027
TI  - Quantifying the risk of error when interpreting funnel plots.
AB  - BACKGROUND: Funnel plots are widely used to investigate possible publication bias
      in meta-analyses. There has, however, been little formal assessment of whether a
      visual inspection of a funnel plot is sufficient to identify publication bias.
      METHODS: Visual assessment of bias in a funnel plot is quantified using two new
      statistics: the Imbalance and the Asymmetry Distance, both intended to replicate
      how a funnel plot is typically assessed. A simulation study was performed to
      assess the performance of these two statistics for identifying publication bias.
      RESULTS: The two statistics both have high type I error and low statistical
      power, unless the number of studies in the meta-analysis is very large. These
      results suggest that visual inspection of a funnel plot is unlikely to lead to a
      valid assessment of publication bias. CONCLUSIONS: In most systematic reviews,
      visual inspection of a funnel plot may give a misleading impression of the
      presence or absence of publication bias. Formal statistical tests for bias should
      generally be preferred.

PMID- 25875028
TI  - A colorimetric and absorption ratiometric anion sensor based on indole &
      hydrazide binding units.
AB  - A colorimetric and absorption ratiometric anion sensor (L) based on indole and
      hydrazide binding units was designed and synthesized, and its recognition &
      sensing properties towards different anions were studied by naked-eye
      observations, UV-vis and (1)H NMR titration spectra. Sensor L could selectively
      recognize biologically important F(-), AcO(-) and H2PO4(-) in DMSO over other
      anions, along with a significant change in its color and absorption spectrum,
      resulting from the formation of corresponding 1:2 (L/F(-)) and 1:1 (L/AcO(-) and
      L/H2PO4(-)) complexes. The (1)H NMR titration experiments proved that sensor L
      experienced deprotonation of NH fragment and produced [HF2](-) species, whereas a
      stable H-bonding complex was formed in the presence of AcO(-) and H2PO4(-). 

PMID- 25875029
TI  - Visible light absorption and photo-sensitizing properties of spinach leaves and
      beetroot extracted natural dyes.
AB  - Herein, chlorophyll and betalain dyes are extracted from fresh spinach leaves and
      beetroots. Fourier transform infrared spectra are used to identify the
      characteristic peaks of the extracted dyes. UV-vis light absorption
      characteristics of the dyes and their mixed counterpart are investigated by
      varying their pH and temperature. These dyes are used as photo sensitizer for
      fabrication of zinc oxide photo-anode based dye sensitized solar cells (DSSCs).
      The photo-voltaic characteristics of the developed DSSCs are measured under
      simulated solar light (power of incident light 100 mW cm(-2) from Air Mass 1.5G).
      The solar to electric conversion efficiencies for the chlorophyll, betalain and
      mixed dye based solar cells are estimated as 0.148%, 0.197% and 0.294%
      respectively. The highest conversion efficiency for mixed dye based solar cell is
      attributed due to the absorption of wider range of solar spectrum.

PMID- 25875030
TI  - Synchronous spectrofluorimetric study of the supramolecular host-guest
      interaction of beta-cyclodextrin with propranolol: A comparative study.
AB  - The objective of this work is to assess the use of constant-wavelength
      synchronous fluorescence spectroscopy (SFS) in comparison to conventional
      fluorescence spectroscopy (CFS) for the investigation of the supramolecular host
      guest interaction of beta-CD with propranolol (PPL) in aqueous solutions.
      Scanning for the optimal Deltalambda at which the SFS can be performed in the
      presence of beta-CD was examined. The results obtained revealed three
      distinguishable shapes for PPL using SFS that can be represented by three
      different Deltalambda values, namely 10, 40, and 100 nm. However, the effect of
      the beta-CD concentration on the fluorescence intensity of PPL was examined using
      CFS and SFS of PPL at a Deltalambda of 10 and 100 nm. The change in the
      fluorescence intensity was used to calculate the equilibrium constant (Keq) for
      the formation of the beta-CD:PPL inclusion complex by applying the Benesi
      Hildebrand method. Keq values of 108, 112, and 117 M(-1) were obtained using SFS
      with a Deltalambda of 10 and 100 nm, and CFS, respectively. Further, the SFS
      method was successfully employed to examine the iodide quenching effect on the
      fluorescence intensity of PPL, where the results obtained revealed a Stern-Volmer
      quenching constant of 42.8 M(-1), which is in good agreement with results
      obtained using CFS. All results obtained using the SFS method were compared with
      the results obtained using the CFS method.

PMID- 25875031
TI  - Stability and efficiency of dye-sensitized solar cells based on papaya-leaf dye.
AB  - The present article reports on the enhancement of the performance and stability
      of natural dye-based dye-sensitized solar cells (DSSCs). Natural dyes extracted
      from papaya leaves (PL) were investigated as sensitizers in TiO2-based DSSCs and
      evaluated in comparison with N719 dye. The acidity of the papaya-leaf extract
      dyes was tuned by adding benzoic acid. The TiO2 film-coated fluorine-doped tin
      oxide glass substrates were prepared using the doctor-blade method, followed by
      sintering at 450  degrees C. The counter electrode was coated by chemically
      deposited catalytic platinum. The working electrodes were immersed in N719 dye
      and papaya dye solutions with concentrations of 8 g/100 mL. The absorbance
      spectra of the dyes were obtained by ultra-violet-visible spectroscopy. The
      energy levels of the dyes were measured by the method of cyclic voltammetry. In
      addition, Fourier transform infrared spectroscopy was used to determine the
      characteristic functionalities of the dye molecules. The DSSC based on the N719
      dye displayed a highest efficiency of 0.87% whereas those based on papaya-leaf
      dye achieved 0.28% at pH 3.5. The observed improved efficiency of the latter was
      attributed to the increased current density value. Furthermore, the DSSCs based
      on papaya-leaf dye with pH 3.5-4 exhibited better stability than those based on
      N719 dye. However, further studies are required to improve the current density
      and stability of natural dye-based DSSCs, including the investigation of
      alternative dye extraction routes, such as isolating the pure chlorophyll from
      papaya leaves and stabilizing it.

PMID- 25875032
TI  - Studies of the photophysics of highly fluorescent Red Mega 480 laser dye in
      solutions: Steady state spectroscopy.
AB  - The absorption and fluorescence spectra of highly fluorescent industrially useful
      medium sized Red Mega 480 dye have been studied in various solvents at 298 K. The
      solute photophysical behavior depends strongly on the solute-solvent
      interactions. In order to understand the effect of inter molecular interactions
      on spectral behaviors of the dye in different solvents extent of this behavior
      can be analyzed by linear solvation energy relationships. In addition, ground and
      excited state dipole moments were evaluated by various methods. It is observed
      that excited state dipole moment (MUe) is larger than the ground state (MUg),
      absorption spectra show a bathochromic shift with increasing polarity indicating
      that transition involved is pi->pi(*) and Onsager cavity radius is determined by
      atomic increment method.

PMID- 25875033
TI  - Time-resolved fluorescence sensing of pesticides chlorpyrifos, crotoxyphos and
      endosulfan by the luminescent Eu(III)-8-allyl-3-carboxycoumarin probe.
AB  - This work describes the application of time resolved fluorescence in microtiter
      plates for investigating the interactions of europium-allyl-3-carboxycoumarin
      with pesticides chlorpyrifos, endosulfan and crotoxyphos. Stern-Volmer studies at
      different temperatures for chlorpyrifos and crotoxyphos shows dynamic and static
      quenching mechanisms respectively. Direct methods for the determination of the
      pesticides under investigation have been developed using the luminescence
      variations of the probe in solution. The detection limits are 6.53, 0.004, 3.72
      MUmol/L for chlorpyrifos, endosulfan, and crotoxyphos, respectively. The binding
      constants and thermodynamic parameters of the pesticides with probe were
      evaluated. A thermodynamic analysis showed that the reaction is spontaneous with
      negative DeltaG. Effect of some relevant interferents on the detection of
      pesticides has been investigated. The new method was applied to the determination
      of the pesticides in different types of water samples (tap, mineral, and waste
      water).

PMID- 25875034
TI  - Spectrofluorimetric determination of ofloxacin in milk with N-(9
      fluorenylmethyloxycarbonyl)-L-alanine.
AB  - It was found that N-(9-fluorenylmethyloxycarbonyl)-L-alanine (F-Ala) could
      interact with ofloxacin (OFL) and enhance the fluorescence of OFL, which could be
      used to set up a new fluorescence spectrophotometry method to detect OFL without
      isolation procedure. The experimental conditions were discussed and when MeOH was
      used as solvent, 0.001 MUg mL(-1) of OFL could be detected. For making the method
      could be used easily in milk samples, MeOH/H2O (v/v, 4:1, pH 4.1) was used as the
      optimal solvent condition, the limit of quantification of OFL could be reached
      0.01 MUg mL(-1) in milk samples with recovery more than 88% at least.

PMID- 25875035
TI  - Sn-doped TiO2 nanotubes as superior anode materials for sodium ion batteries.
AB  - Sn-doped TiO2 nanotubes were employed as anodes for sodium ion batteries. The
      electrodes exhibit a high maximum charge capacity of 257 mA h g(-1) after 50
      cycles at a current density of 50 mA g(-1) with good rate capability and
      especially excellent cycling stability, mainly due to the increase of electrical
      conductivity by Sn doping. 

PMID- 25875036
TI  - The association of brachial-ankle pulse wave velocity with coronary artery
      disease evaluated by coronary computed tomography angiography.
AB  - The aim of this study was to investigate whether brachial-ankle pulse wave
      velocity (baPWV) is associated with the severity of coronary artery disease (CAD)
      assessed by coronary computed tomography angiography (CCTA), and to evaluate
      baPWV as a predictor of obstructive CAD on CCTA. A total of 470 patients who
      underwent both baPWV and CCTA were included. We evaluated stenosis degree and
      plaque characteristics on CCTA. To estimate the severity of CAD, we calculated
      the number of segment with plaque (segment involvement score; SIS), stenosis
      degree-weighted plaque score (segment stenosis score; SSS), and coronary artery
      calcium score (CACS). The mean baPWV was 1,485 +/- 315 cm/s (range, 935-3,175
      cm/s). Non-obstructive (stenosis < 50%) and obstructive (stenosis >= 50%) CAD was
      found in 129 patients (27.4%) and 144 (30.6%), respectively. baPWV in patients
      with obstructive CAD was higher than that of patients with non-obstructive (1,680
      +/- 396 cm/s versus 1,477 +/- 244 cm/s, P < 0.001) or no CAD (1,680 +/- 396 cm/s
      versus +/- 196 1,389 cm/s, P < 0.001). baPWV showed significant correlation with
      SSS (r = 0.429, P < 0.001), SIS (r = 0.395, P < 0.001), CACS (r 0.346, P <
      0.001), and the number of segment with non-calcified plaque (r 0.092, P = 0.047),
      mixed plaque (r = 0.267, P < 0.001), and calcified plaque (r = 0.348, P < 0.001),
      respectively. The optimal baPWV cut-off value for the detection of obstructive
      CAD was 1,547 cm/s. baPWV >= 1,547 cm/s was independent predictor for the
      obstructive CAD. In conclusion, baPWV is well correlated with the severity of CAD
      evaluated by CCTA. baPWV has the potential to predict severity of coronary artery
      atherosclerosis. 

PMID- 25875037
TI  - First-principles calculations, experimental study, and thermodynamic modeling of
      the Al-Co-Cr system.
AB  - The phase relations and thermodynamic properties of the condensed Al-Co-Cr
      ternary alloy system are investigated using first-principles calculations based
      on density functional theory (DFT) and phase-equilibria experiments that led to X
      ray diffraction (XRD) and electron probe micro-analysis (EPMA) measurements. A
      thermodynamic description is developed by means of the calculations of phase
      diagrams (CALPHAD) method using experimental and computational data from the
      present work and the literature. Emphasis is placed on modeling the bcc-A2, B2,
      fcc-gamma, and tetragonal-sigma phases in the temperature range of 1173 to 1623
      K. Liquid, bcc-A2 and fcc-gamma phases are modeled using substitutional solution
      descriptions. First-principles special quasirandom structures (SQS) calculations
      predict a large bcc-A2 (disordered)/B2 (ordered) miscibility gap, in agreement
      with experiments. A partitioning model is then used for the A2/B2 phase to
      effectively describe the order-disorder transitions. The critically assessed
      thermodynamic description describes all phase equilibria data well. A2/B2
      transitions are also shown to agree well with previous experimental findings. 

PMID- 25875038
TI  - Phenylglyoxal-based visualization of citrullinated proteins on Western blots.
AB  - Citrullination is the conversion of peptidylarginine to peptidylcitrulline, which
      is catalyzed by peptidylarginine deiminases. This conversion is involved in
      different physiological processes and is associated with several diseases,
      including cancer and rheumatoid arthritis. A common method to detect
      citrullinated proteins relies on anti-modified citrulline antibodies directed to
      a specific chemical modification of the citrulline side chain. Here, we describe
      a versatile, antibody-independent method for the detection of citrullinated
      proteins on a membrane, based on the selective reaction of phenylglyoxal with the
      ureido group of citrulline under highly acidic conditions. The method makes use
      of 4-azidophenylglyoxal, which, after reaction with citrullinated proteins, can
      be visualized with alkyne-conjugated probes. The sensitivity of this procedure,
      using an alkyne-biotin probe, appeared to be comparable to the antibody-based
      detection method and independent of the sequence surrounding the citrulline. 

PMID- 25875039
TI  - Four new pentasaccharide resin glycosides from Ipomoea cairica with strong alpha
      glucosidase inhibitory activity.
AB  - Six pentasaccharide resin glycosides from Ipomoea cairica, including four new
      acylated pentasaccharide resin glycosides, namely cairicoside I-IV (1-4) and the
      two known compounds cairicoside A (5) and cairicoside C (6), were isolated from
      the aerial parts of Ipomoea cairica. Their structures were established by a
      combination of spectroscopic, including two dimensional (2D) NMR and chemical
      methods. The core of the six compounds was simonic acid A, and they were
      esterfied the same sites, just differing in the substituent groups. The
      lactonization site of the aglycone was bonded to the second saccharide moiety at
      C-2 in 1-4, and at C-3 in 5-6. Compounds 1 and 5, 4 and 6 were two pairs of
      isomers. The absolute configuration of the aglycone in 1-6 which was (11S)
      hydroxyhexadecanoic acid (jalapinolic acid) was established by Mosher's method.
      Compounds 1-4 have been evaluated for inhibitory activity against alpha
      glucosidase, which all showed inhibitory activities. 

PMID- 25875040
TI  - Employing response surface methodology for the optimization of ultrasound
      assisted extraction of lutein and beta-carotene from spinach.
AB  - The extraction of lutein and beta-carotene from spinach (Spinacia oleracea L.)
      leaves is important to the dietary supplement industry. A Box-Behnken design and
      response surface methodology (RSM) were used to investigate the effect of process
      variables on the ultrasound-assisted extraction (UAE) of lutein and beta-carotene
      from spinach. Three independent variables, extraction temperature ( degrees C),
      extraction power (%) and extraction time (min) were studied. Thin-layer
      chromatography (TLC) followed by UV visualization and densitometry was used as a
      simple and rapid method for both identification and quantification of lutein and
      beta-carotene during UAE. Methanol extracts of leaves from spinach and authentic
      standards of lutein and beta-carotene were separated by normal-phase TLC with
      ethyl acetate-acetone (5:4 (v/v)) as the mobile phase. In this study, the
      combination of TLC, densitometry, and Box-Behnken with RSM methods were effective
      for the quantitative analysis of lutein and beta-carotene from spinach extracts.
      The resulting quadratic polynomial models for optimizing lutein and beta-carotene
      from spinach had high coefficients of determination of 0.96 and 0.94,
      respectively. The optimal UAE settings for output of lutein and beta-carotene
      simultaneously from spinach extracts were an extraction temperature of 40 
      degrees C, extraction power of 40% (28 W/cm3) and extraction time of 16 min. The
      identity and purity of each TLC spot was measured using time-of-flight mass
      spectrometry. Therefore, UAE assisted extraction of carotenes from spinach can
      provide a source of lutein and beta-carotene for the dietary supplement industry.

PMID- 25875041
TI  - Epigallocatechin-3-gallate protects HUVECs from PM2.5-induced oxidative stress
      injury by activating critical antioxidant pathways.
AB  - Endothelial dysfunction and oxidative stress likely play roles in PM2.5-induced
      harmful effects. Epigallocatechin-3-gallate (EGCG), the major polyphenolic
      constituent of green tea, is a potent antioxidant that exerts protective effects
      on cardiovascular diseases (CVDs) in part by scavenging free radicals. The
      exposure to ambient fine particulate matter (PM2.5) is responsible for certain
      CVDs. The aim of the present study was to investigate whether EGCG could also
      inhibit PM2.5-induced oxidative stress by activating the nuclear factor E2
      related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway in human umbilical vein
      endothelial cells (HUVECs). PM2.5 (200 MUg/mL) increased both cell death and
      intracellular ROS levels significantly, whereas EGCG (50-400 MUM) inhibited these
      effects in a concentration-dependent manner. Western blotting and PCR
      demonstrated that EGCG increased Nrf2 and HO-1 expression in HUVECs that had been
      exposed to PM2.5. PD98059 (a selective inhibitor of extracellular signal
      regulated kinase [ERK]-1/2) and SB203580 (a selective inhibitor of p38 MAPK), but
      not SP600125 (a selective inhibitor of c-jun N-terminal kinase [JNK]), attenuated
      the EGCG-induced Nrf2 and HO-1 expression. In addition, silencing Nrf2 abolished
      EGCG-induced Nrf2 and HO-1 upregulation and enhancement of cell viability. The
      present study suggests that EGCG protects HUVECs from PM2.5-induced oxidative
      stress injury by upregulating Nrf2/HO-1 via activation of the p38 MAPK and the
      ERK1/2 signaling pathways. 

PMID- 25875042
TI  - A three-enzyme-system to degrade curcumin to natural vanillin.
AB  - The symmetrical structure of curcumin includes two 4-hydroxy-3-methoxyphenyl
      substructures. Laccase catalyzed formation of a phenol radical, radical migration
      and oxygen insertion at the benzylic positions can result in the formation of
      vanillin. As vanillin itself is a preferred phenolic substrate of laccases, the
      formation of vanillin oligomers and polymers is inevitable, once vanillin becomes
      liberated. To decelerate the oligomerization, one of the phenolic hydroxyl groups
      was protected via acetylation. Monoacetyl curcumin with an approximate molar
      yield of 49% was the major acetylation product, when a lipase from Candida
      antarctica (CAL) was used. In the second step, monoacetyl curcumin was incubated
      with purified laccases of various basidiomycete fungi in a biphasic system
      (diethyl ether/aqueous buffer). A laccase from Funalia trogii (LccFtr) resulted
      in a high conversion (46% molar yield of curcumin monoacetate) to vanillin
      acetate. The non-protected vanillin moiety reacted to a mixture of higher
      molecular products. In the third step, the protecting group was removed from
      vanillin acetate using a feruloyl esterase from Pleurotus eryngii (PeFaeA) (68%
      molar yield). Alignment of the amino acid sequences indicated that high potential
      laccases performed better in this mediator and cofactor-free reaction. 

PMID- 25875043
TI  - Multiple programmed cell death pathways are involved in N-methyl-N-nitrosourea
      induced photoreceptor degeneration.
AB  - PURPOSE: To identify programmed cell death (PCD) pathways involved in N-methyl-N
      nitrosourea (MNU)-induced photoreceptor (PR) degeneration. METHODS: Adult C57BL/6
      mice received a single MNU i.p. injection (60 mg/kg bodyweight), and were
      observed over a period of 7 days. Degeneration was visualized by H&E overview
      staining and electron microscopy. PR cell death was measured by quantifying TUNEL
      positive cells in the outer nuclear layer (ONL). Activity measurements of key PCD
      enzymes (calpain, caspases) were used to identify the involved cell death
      pathways. Furthermore, the expression level of C/EBP homologous protein (CHOP)
      and glucose-regulated protein 78 (GRP78), key players in endoplasmic reticulum
      (ER) stress-induced apoptosis, was analyzed using quantitative real-time PCR.
      RESULTS: A decrease in ONL thickness and the appearance of apoptotic PR nuclei
      could be detected beginning 3 days post-injection (PI). This was accompanied by
      an increase of TUNEL-positive cells. Significant upregulation of activated
      caspases (3, 9, 12) was found at different time periods after MNU injection.
      Additionally, several other players of nonconventional PCD pathways were also
      upregulated. Consequently, calpain activity increased in the ONL, with a maximum
      on day 7 PI and an upregulation of CHOP and GRP78 expression beginning on day 1
      PI was found. CONCLUSIONS: The data indicate that regular apoptosis is the major
      cause of MNU-induced PR cell death. However, alternative PCD pathways, including
      ER stress and calpain activation, are also involved. Knowledge about the
      mechanisms involved in this mouse model of PR degeneration could facilitate the
      design of putative combinatory therapeutic approaches.

PMID- 25875044
TI  - Combined silencing of TGF-beta2 and Snail genes inhibit epithelial-mesenchymal
      transition of retinal pigment epithelial cells under hypoxia.
AB  - BACKGROUND: The formation of scar-like fibrous tissue in age-related macular
      degeneration (AMD) is associated with hypoxia. Under hypoxia, retinal pigment
      epithelial (RPE) cells can secret more transforming growth factor-beta2 (TGF
      beta2), which is determined to induce epithelial-mesenchymal transition (EMT) at
      certain concentrations. Whether hypoxia can induce EMT by stimulating RPE cell
      line secrets TGF-beta2 or not remains unknown. To gain a better understanding of
      the signaling mechanisms of fibrosis in AMD under hypoxic conditions, we
      investigated EMT in retinal pigment epithelial (RPE) cells and the effect of TGF
      beta2 and Snail in this process. METHODS: Human RPE cell line (ARPE-19) was
      incubated with 5 % O2 for different periods of time. The expression of N
      cadherin, alpha-smooth muscle actin (alpha-SMA), TGF-beta2 , and Snail were
      determined by Western blot and real-time PCR. Cell proliferation was assessed by
      CCK8 kit. RNA interference was used for multi-gene silencing of TGF-beta2 and
      Snail genes. RESULTS: N-cadherin was decreased and mesenchymal cell marker alpha
      SMA was increased after the ARPE-19 cell line was incubated with 5 % O2.
      Meanwhile, the proliferation capability of the cell line was increased. TGF-beta2
      and Snail expression were increased in a time-dependent manner under hypoxia.
      After multi-silencing TGF-beta2 and Snail genes, N-cadherin was increased and
      alpha-SMA was reduced. Meanwhile, the proliferation of the cell line was
      suppressed. CONCLUSIONS: Under hypoxic conditions, RPE cells undergo EMT.
      Endogenic TGF-beta2 and Snail are involved in this process. Furthermore,
      knockdown of both TGF-beta2 and Snail inhibited EMT to a greater extent than
      knockdown of either gene individually.

PMID- 25875045
TI  - Involvement of mTOR in Type 2 CRF Receptor Inhibition of Insulin Signaling in
      Muscle Cells.
AB  - Type 2 corticotropin-releasing factor receptor (CRFR2) is expressed in skeletal
      muscle and stimulation of the receptor has been shown to inhibit the effect of
      insulin on glucose uptake in muscle cells. Currently, little is known about the
      mechanisms underlying this process. In this study, we first showed that both in
      vivo and in vitro CRFR2 expression in muscle was closely correlated with insulin
      sensitivity, with elevated receptor levels observed in insulin resistant muscle
      cells. Stimulation of CRFR2 by urocortin 2 (Ucn 2), a CRFR2-selective ligand, in
      C2C12 myotubes greatly attenuated insulin-induced glucose uptake. The inhibitory
      effect of CRFR2 signaling required cAMP production and is involved the mammalian
      target of rapamycine pathway, as rapamycin reversed the inhibitory effect of
      CRFR2 stimulation on insulin-induced glucose uptake. Moreover, stimulation of
      CRFR2 failed to inhibit glucose uptake in muscle cells induced by platelet
      derived growth factor, which, similar to insulin, signals through Akt-mediated
      pathway but is independently of insulin receptor substrate (IRS) proteins to
      promote glucose uptake. This result argues that CRFR2 signaling modulates
      insulin's action likely at the levels of IRS. Consistent with this notion, Ucn 2
      reduced insulin-induced tyrosine phosphorylation of IRS-1, and treatment with
      rapamycin reversed the inhibitory effect of Ucn 2 on IRS-1 and Akt
      phosphorylation. In conclusion, the inhibitory effect of CRFR2 signaling on
      insulin action is mediated by cAMP in a mammalian target of rapamycine-dependent
      manner, and IRS-1 is a key nodal point where CRFR2 signaling modulates insulin
      stimulated glucose uptake in muscle cells. 

PMID- 25875046
TI  - Roles of progesterone receptor A and B isoforms during human endometrial
      decidualization.
AB  - Progesterone, acting through the progesterone receptors (PGRs), is one of the
      most critical regulators of endometrial differentiation, known as
      decidualization, which is a key step toward the establishment of pregnancy. Yet a
      long-standing unresolved issue in uterine biology is the precise roles played by
      the major PGR isoforms, PGR-A and PGR-B, during decidualization in the human. Our
      approach, expressing PGR-A and PGR-B individually after silencing endogenous PGRs
      in human endometrial stromal cells (HESCs), enabled the analysis of the roles of
      these isoforms separately as well as jointly. Chromatin immunoprecipitation
      sequencing in combination with gene expression profiling revealed that PGR-B
      controls a substantially larger cistrome and transcriptome than PGR-A during HESC
      differentiation. Interestingly, PGR-B directly regulates the expression of PGR-A.
      De novo motif analysis indicated that, although the 2 isoforms bind to the same
      DNA sequence motif, there are both common and unique neighboring motifs where
      other transcription factors, such as FOSL1/2, JUN, C/EBPbeta, and STAT3, bind and
      dictate the transcriptional activities of these isoforms. We found that PGR-A and
      PGR-B regulate overlapping as well as distinct sets of genes, many of which are
      known to be critical for decidualization and establishment of pregnancy. When PGR
      A and PGR-B were coexpressed during HESC differentiation, PGR-B played a
      predominant role, although both isoforms influenced each other's transcriptional
      activity. This study revealed the gene networks that operate downstream of each
      PGR isoform to mediate critical functions, such as regulation of the cell cycle,
      angiogenesis, lysosomal activation, insulin receptor signaling, and apoptosis,
      during decidualization in the human. 

PMID- 25875047
TI  - Spatial decoupling of targets and flashing stimuli for visual brain-computer
      interfaces.
AB  - OBJECTIVE: Recently, paradigms using code-modulated visual evoked potentials (c
      VEPs) have proven to achieve among the highest information transfer rates for
      noninvasive brain-computer interfaces (BCIs). One issue with current c-VEP
      paradigms, and visual-evoked paradigms in general, is that they require direct
      foveal fixation of the flashing stimuli. These interfaces are often visually
      unpleasant and can be irritating and fatiguing to the user, thus adversely
      impacting practical performance. In this study, a novel c-VEP BCI paradigm is
      presented that attempts to perform spatial decoupling of the targets and flashing
      stimuli using two distinct concepts: spatial separation and boundary positioning.
      APPROACH: For the paradigm, the flashing stimuli form a ring that encompasses the
      intended non-flashing targets, which are spatially separated from the stimuli.
      The user fixates on the desired target, which is classified using the changes to
      the EEG induced by the flashing stimuli located in the non-foveal visual field.
      Additionally, a subset of targets is also positioned at or near the stimulus
      boundaries, which decouples targets from direct association with a single
      stimulus. This allows a greater number of target locations for a fixed number of
      flashing stimuli. MAIN RESULTS: Results from 11 subjects showed practical
      classification accuracies for the non-foveal condition, with comparable
      performance to the direct-foveal condition for longer observation lengths. Online
      results from 5 subjects confirmed the offline results with an average accuracy
      across subjects of 95.6% for a 4-target condition. The offline analysis also
      indicated that targets positioned at or near the boundaries of two stimuli could
      be classified with the same accuracy as traditional superimposed (non-boundary)
      targets. SIGNIFICANCE: The implications of this research are that c-VEPs can be
      detected and accurately classified to achieve comparable BCI performance without
      requiring potentially irritating direct foveation of flashing stimuli.
      Furthermore, this study shows that it is possible to increase the number of
      targets beyond the number of stimuli without degrading performance. Given the
      superior information transfer rate of c-VEP paradigms, these results can lead to
      the development of more practical and ergonomic BCIs.

PMID- 25875048
TI  - Translation into Greek and initial validity and reliability testing of a modified
      version of the SCIM III, in both English and Greek, for self-use.
AB  - PURPOSE: To translate and culturally adapt the Spinal Cord Injury Measure version
      III (SCIM III) into Greek (GR-SCIM III). To conduct initial testing of
      psychometric properties of both measures by self-report. METHOD: Forward-backward
      translation was conducted to produce the GR-SCIM III. Participants completed the
      English or Greek versions in 2008-2009. Both versions were examined for
      multidimensionality, internal consistency and concurrent/criterion validity with
      the EQ-5D. RESULTS: Forty-five Greek adults with spinal cord injury (SCI) (23
      males), mean age 61 (SD17) years; mean time since injury 11 (SD9) years,
      completed the GR-SCIM III. One hundred and seventy four English-speaking adults
      with SCI (111 males), mean age 47 (SD12) years; mean time since injury 12 (SD11)
      years, completed the SCIM III. Unidimensionality was confirmed for both versions.
      Internal consistency was acceptable (alpha = 0.78 for both). Validity was strong
      for the "self-care" subscale (GR-SCIM III rho = -0.78, SCIM III rho = -0.75) and
      moderate for the "mobility" subscale (GR-SCIM III rho = -0.58, SCIM III rho = 
      0.45). CONCLUSIONS: This has been the first function scale translated and
      validated in Greek for people with SCI. Both the GR-SCIM III and SCIM III are
      reliable for use by self-report. More studies are needed to further examine their
      psychometric properties and compare with observation or interview. IMPLICATIONS
      FOR REHABILITATION: The Greek version of the Spinal Cord Independence Measure
      version III (SCIM) is valid and reliable for self-report. Further testing is
      needed to assess psychometric qualities not assessed in the present study.
      Researchers and therapists in Greece can use a specific measure to assess
      functional independence in people with Spinal Cord Injury (SCI). Consideration
      needs to be given to the participants' type of injury, which may affect the
      results of SCIM III.

PMID- 25875049
TI  - A Pilot Study: examining the effects and tolerability of structured dance
      intervention for individuals with multiple sclerosis.
AB  - PURPOSE: The aims of this pilot were to examine dance as a feasible intervention
      for persons with multiple sclerosis (MS), specifically to examine issues of
      tolerability and its longitudinal effects on participants. Dance is an enjoyable
      physical activity that has been investigated in other neurodegenerative
      populations but has yet to be studied in MS. METHOD: A 4-week, two 60-min classes
      per week, pilot salsa dance intervention was administered to eight individuals
      with MS. The outcomes measured were effects on gait, balance, self-efficacy,
      motivation, physical activity and MS symptoms. They were administered at
      baseline, immediately post-intervention and at 3- and 6-month follow-ups.
      RESULTS: Statistically significant pre-post intervention gains were found for the
      Timed Up and Go Test (TUG), Dynamic Gait Index (DGI), Activities-specific Balance
      Confidence Scale and Godin Leisure Time Questionnaire. Significant improvements
      were also found for the TUG, DGI and MS Walking Scale between baseline and 3
      month follow-up assessments. Participants did not report any problems with
      fatigue or intolerability with the 60-min suggestions, further supporting the
      feasibility for the concept of a dance intervention. CONCLUSIONS: This study
      suggests that dance for persons with MS may have promise for improving physical
      activity, gait and balance. IMPLICATIONS FOR REHABILITATION: Although structured
      dance has reported benefits in elderly populations and in individuals with
      cardiovascular and neurological impairments, there is virtually nothing known
      regarding dance in the MS population. This pilot salsa dance study shows that
      structured dance demonstrates promise of being well-tolerated, safe and effective
      at promoting physical activity in people with MS without increased fatigue. A 12
      week study has been initiated to test the robustness of initial observations and
      further examine factors influencing participants' physical activity adherence and
      behavioral change.

PMID- 25875050
TI  - Rehabilitation Complexity Scale: Italian translation and transcultural
      validation.
AB  - PURPOSE: The aim of the present study was translation, cultural adaption and
      validation of the extended version 12 of the Rehabilitation Complexity Scale (RCS
      E) in a sample of patients with stroke and total hip replacement. METHOD: The
      cross-cultural validation required RCS-E forward-backward translation, revision
      by an expert committee and its application in an Intensive Rehabilitation setting
      through a retrospective collection of data from clinical records. The evaluation
      of the psychometric properties was carried out by analyzing the correlations
      between RCS-E score and other measures (Functional Independence Measure, Braden,
      Morse, Cumulative Illness Rating Scale) and the assessment of reliability in
      terms of reproducibility (inter-observer agreement) and repeatability (intra
      observer agreement). RESULTS: The backward and forward processes of translation
      of the scale did not create problems of interpretation of terms. Some adaptation
      was required for the items nursing (N), medical care (M) and therapeutic
      intensity (TI) due to differences on the national health system structure. The
      Italian version of the scale proved to be valid, reliable with high
      reproducibility and repeatability. CONCLUSIONS: The Italian version RCS-E has
      been successfully validated, showing good psychometric properties, which partly
      reproduce the results obtained for the original version. However, some assumption
      was made for some items thus preventing possible comparison with other countries.
      IMPLICATIONS FOR REHABILITATION: Admittance at an Intensive Rehabilitation care
      setting in Italy requires to evaluate the complexity of rehabilitation needs. The
      Rehabilitation Complexity Scale (RCS-E) has proved to be reliable for assessing
      clinical complexity and consequently for planning rehabilitation needs. The
      Italian version of RCS-E has been successfully validated, showing good
      psychometric properties, which reproduce the results obtained for the original
      version. The items included in the therapy intensity subscale do not fit the
      Italian health system rules for intensity of rehabilitation care and needs
      adaptation.

PMID- 25875051
TI  - Enhanced electric dipole transition in lanthanide complex with organometallic
      ruthenocene units.
AB  - Enhanced luminescence of a lanthanide complex with dynamic polarization of the
      excited state and molecular motion is introduced. The luminescent lanthanide
      complex is composed of one Eu(hfa)3 (hfa, hexafluoroacetylacetonate) and two
      phosphine oxide ligands with ruthenocenyl units Rc, [Eu(hfa)3(RcPO)2] (RcPO =
      diphenylphosphorylruthenocene). The ruthenocenyl units in the phosphine oxide
      ligands play an important role of switching for dynamic molecular polarization
      and motion in liquid media. The oxidation states of the ruthenocenyl unit
      (Rc(1+)/Rc(1+)) are controlled by potentiostatic polarization. Eu(III) complexes
      attached with bidentate phosphine oxide ligands containing ruthenocenyl units,
      [Eu(hfa)3(RcBPO)] (RcBPO = 1,1'-bis(diphenylphosphoryl)ruthenocene), and with
      bidentate phosphine oxide ligands, [Eu(hfa)3(BIPHEPO)] (BIPHEPO =1,1'-biphenyl
      2,2'-diylbis(diphenylphosphine oxide), were also prepared as references. The
      coordination structures and electrochemical properties were analyzed using single
      crystal X-ray analysis, cyclic voltammetry, and absorption spectroscopy
      measurements. The luminescence properties were estimated using an
      optoelectrochemical cell. Under potentiostatic polarization, a significant
      enhancement of luminescence was successfully observed for [Eu(hfa)3(RcPO)2],
      while no spectral change was observed for [Eu(hfa)3(RcBPO)]. In this study, the
      remarkable enhanced luminescence phenomena of Eu(III) complex based on the
      dynamic molecular motion under potentiostatic polarization have been performed. 

PMID- 25875052
TI  - Occurrence of Psoriasiform Eruption During Nivolumab Therapy for Primary Oral
      Mucosal Melanoma.

PMID- 25875053
TI  - Near-infrared and naked-eye fluorescence probe for direct and highly selective
      detection of cysteine and its application in living cells.
AB  - The near-infrared (NIR) fluorescence sensor for rapid, selective, and sensitive
      detection of cystenine (Cys) is of great importance in both biological and
      environmental sciences. Herein, we report a specific probe with turn-on
      fluorescence property, visible color change with naked-eye, and large wavelength
      shift on UV spectra for highly selective detection of Cys over homocysteine (Hcy)
      and glutathione (GSH) in both HEPES buffer (10 mM, pH 7.4) and diluted human
      serum. The probe based on the conjugate addition-cyclization reaction has a low
      limit of detection to Cys (0.16 MUM as NIR fluorescence sensor and 0.13 MUM as UV
      sensor). Kinetic study indicated that the probe has a very rapid response to Cys,
      owing to the much higher pseudo-first-order reaction constant with Cys (299 M(-1)
      s(-1)) than with Hcy (1.29 M(-1) s(-1)) or GSH (0.53 M(-1) s(-1)). Upon addition
      of Cys to a solution of the probe, the color changed from purple to cyan, with
      the maximum wavelength shifting from 582 to 674 nm in the UV spectrum and a
      fluorescence emission at 697 nm appearing. It has been successfully applied for
      determination of Cys in diluted serum and bioimaging of Cys in living cells with
      low cell toxicity. 

PMID- 25875054
TI  - Correction to GPR103 Antagonists Demonstrating Anorexigenic Activity in Vivo:
      Design and Development of Pyrrolo[2,3-c]pyridines That Mimic the C-Terminal Arg
      Phe Motif of QRFP26.

PMID- 25875055
TI  - A double-enhanced strip biosensor for the rapid and ultrasensitive detection of
      protein biomarkers.
AB  - Combining the specific molecular recognition reaction between biotin and
      streptavidin with a dual-class signal amplification system, containing the unique
      optical properties of gold nanoparticles and the catalytic reaction of
      horseradish peroxidase, a double-enhanced strip biosensor was designed for the
      first time for a visual and rapid detection of protein biomarkers with good
      accuracy, especially for CEA with a detection limit of 2.9 fg mL(-1). 

PMID- 25875058
TI  - Muted voices: HIV/AIDS and the young people of Burkina Faso and Senegal.
AB  - This article explores the discrepancies between the vocal public discourse on
      HIV/AIDS and sexuality as generally encouraged by policy-makers and donor
      communities in Africa, and the often hushed voices of their target groups: young
      people in African communities. Based on fieldwork among urban youth in Senegal
      and Burkina Faso, we describe the silence of young people with regard to HIV/AIDS
      and sexuality as a social phenomenon, with focus given to family relations, peer
      relations and gender aspects in partnerships. Drawing on Foucault and Morrell, an
      inability and unwillingness to speak about HIV/AIDS and sexuality are analysed as
      a response to an everyday life characterised by uncertainty. This response
      represents a certain degree of resistance, while it constitutes a major barrier
      to any HIV/AIDS prevention effort. Finally, we stress that despite great
      constraints in their everyday lives, young people have some room to manoeuvre and
      are able to apply some negotiating strategies to reduce sexually-related health
      risks. 

PMID- 25875056
TI  - Crowding-induced cooperativity in DNA surface hybridization.
AB  - High density DNA brush is not only used to model cellular crowding, but also has
      a wide application in DNA-functionalized materials. Experiments have shown
      complicated cooperative hybridization/melting phenomena in these systems, raising
      the question that how molecular crowding influences DNA hybridization. In this
      work, a theoretical modeling including all possible inter and intramolecular
      interactions, as well as molecular details for different species, is proposed. We
      find that molecular crowding can lead to two distinct cooperative behaviours:
      negatively cooperative hybridization marked by a broader transition width, and
      positively cooperative hybridization with a sharper transition, well reconciling
      the experimental findings. Moreover, a phase transition as a result of positive
      cooperativity is also found. Our study provides new insights in crowding and
      compartmentation in cell, and has the potential value in controlling surface
      morphologies of DNA functionalized nano-particles. 

PMID- 25875059
TI  - HIV/AIDS and the South African Bill of Rights, with specific reference to the
      approach and role of the courts.
AB  - An outstanding feature of the 1996 South African Constitution is the inclusion of
      a Bill of Rights, which contains all the categories of human rights that are
      ordinarily included in most international human rights instruments. Section 27
      provides for, among other things, the right to health care services and the right
      to emergency medical treatment. Several other provisions in the Bill of Rights
      are quite relevant to the fight against HIV/AIDS and to protecting the rights of
      those who are infected. The South African courts, particularly the Constitutional
      Court, have often been called upon to interpret and give effect to some of these
      rights. Judgements regarding confidentiality, HIV testing, access to medication
      and related issues have been passed in the courts. In that sense, the courts can
      and have played a pivotal role in the fight against the HIV/AIDS pandemic. In
      spite of that, South Africa is still perceived as a country that has failed to
      address the issue of HIV/AIDS with the urgency that it deserves. This article
      discusses the extent to which the South African Bill of Rights provides for those
      rights relevant to persons with HIV/AIDS and it examines some decisions by the
      courts regarding the enforcement of those rights. The article also explores how
      and whether or not particular court decisions have been implemented and honoured.

PMID- 25875060
TI  - Regional differences in HIV prevalence under prevailing socio-economic
      conditions: a preliminary comparison of north-eastern and southern Africa.
AB  - Preliminary investigation shows that HIV prevalence in north-eastern African
      countries is generally lower than in southern African countries. This has led
      some in the north-east to complacency. Yet, while prevalence levels change
      according to the rate of new infections (incidence) and mortality rate, there are
      indications that the latter may overweigh in north-eastern countries. Given the
      better economic and social welfare conditions in southern African countries,
      infected persons in that region are likely to live longer than those in the north
      eastern grouping. Even so, the level of HIV prevalence in the southern region is
      likely to remain comparatively higher, while the level of incidence may hold
      unchanged. I explore the possible socio-economic factors behind a divergence in
      HIV prevalence in these two regions of sub-Saharan Africa. The work is
      exploratory in intent and scope, primarily aiming to elicit dialogue around
      certain issues and to stress the need for research to better determine the
      existing connections between socio-economic factors and HIV prevalence and
      incidence. Vigorous efforts to combat the epidemic are needed in both north
      eastern and southern African countries. 

PMID- 25875061
TI  - Perception of risk of HIV infection in marital and cohabiting partnerships.
AB  - The purpose of this paper is to understand how married and cohabiting men and
      women define risk and to identify the factors that influence risk perceptions in
      a setting with a high prevalence of HIV infection. A combination of qualitative
      and quantitative methods was used during a cross-sectional survey conducted among
      248 men and 289 women in KwaZulu-Natal, South Africa. Forty in-depth interviews
      were conducted with sexually-active men and women in the same population. The
      majority of men and women perceived themselves at risk of HIV infection. Women
      were more likely than men to report a higher risk of HIV infection. Nearly 46% of
      women and 28% of men perceived themselves at medium or high risk of HIV
      infection. The qualitative and quantitative data show that perception of risk of
      HIV infection was influenced both by a person's own sexual behaviour and a
      partner's sexual behaviour. Men were significantly more likely to perceive
      themselves at risk because of their own risky sexual behaviour (P < 0.01). In
      general, few women reported engaging in risky sexual behaviour. However, women
      were more likely to report that their partners had other sexual partners. Thus,
      women were significantly more likely to perceive themselves at risk because of
      their partner's sexual behaviour (P < 0.05). Also, rural women were significantly
      more likely than urban women to perceive a high risk of HIV infection (P < 0.05).
      Prevention programmes have an important role to play in creating awareness of the
      risk of HIV, especially among men. The belief that they are not at risk of HIV
      infection may result in their failure to adopt self-protective behaviour. 

PMID- 25875062
TI  - Breaking the silence: using memory books as a counselling and succession-planning
      tool with AIDS-affected households in Uganda.
AB  - This article reviews the experience of NACWOLA and Save the Children (UK) in
      using 'memory books' in AIDS-affected households in Uganda from the mid-1990s to
      the present. Semi-structured interviews were carried out with key stakeholders in
      early 2004, including NACWOLA staff and volunteers, Save the Children staff and
      project participants, such as children, counsellors and local government members.
      The aim was to investigate the process by which the Memory Book project was
      developed, its positive and negative impacts at different levels, the costs and
      what lessons had been learned from the experience to date. A number of
      significant constraints are highlighted, but the article concludes that memory
      books, when properly linked to other support mechanisms, have been very effective
      at improving communication and relationships between parents and children,
      confronting stigma in the community and encouraging joint planning for the
      children's future. We recommend that this or similar approaches be incorporated
      in all AIDS programmes. 

PMID- 25875063
TI  - The quality of HIV/AIDS case-detection and case-reporting systems in Mozambique.
AB  - Despite the underlying importance of surveillance systems for the management of
      HIV/AIDS prevention and control programmes, there has been limited analysis of
      the quality of HIV/AIDS case-detection and case-reporting systems, beginning with
      peripheral facilities through to those at national levels. In Mozambique, HIV
      cases are generally correctly detected despite some unreliable use of test kits
      beyond their expiry date, uneven distribution of test kits among facilities,
      frequent disregard for bio-safety measures and irregular external quality
      assessment. Furthermore, HIV/AIDS case-reporting is compromised by poor data
      quality, including under-reporting and discrepancies across different reporting
      channels and organisational levels, as well as a lack of standardised data forms,
      data items collected and report formats. Our analysis of HIV/AIDS surveillance
      systems in Mozambique leads to the following key recommendations: (1) a
      strengthening and standardisation of both the case-detection and case-reporting
      systems at all levels; (2) the regular training of staff at peripheral
      facilities, to allow for better testing and improved local data analysis,
      validation and interpretation; (3) the redesign of reporting systems for blood
      banks, including integration of the AIDS case-reporting subsystems into one; and
      (4) the use of baseline data as a foundation for more comprehensive analysis
      across the country, in response to UNAIDS advice regarding second-generation HIV
      surveillance. 

PMID- 25875064
TI  - Barriers to counselling support for HIV/AIDS patients in south-western Cameroon.
AB  - The potential synergy between counselling and HIV/AIDS prevention is gaining
      recognition in Cameroon as counselling sessions are more often organised at
      health centres. In order to evaluate the actual achievements of these efforts, a
      qualitative ethnographic survey (based on interviews and focus group discussions)
      was conducted in two public and two private hospitals in the South-West Province.
      Churches and public health officials in Cameroon are struggling with the psycho
      social, philosophical, psychological, theological, social, moral, ethical and
      cultural dimensions of HIV/AIDS, as they seek out viable prevention strategies.
      Health centres are also struggling to embrace the full meaning of counselling and
      to make psychological and spiritual support to AIDS patients available through
      the centres. Patients using these health centres may receive HIV testing against
      a backdrop of cultural standards that allow unsafe sex and bar open discussion on
      sex and sexuality. We propose that reversing the trend of the epidemic requires
      the intervention of the State, organisations in civil society and the family.
      Equally crucial is the role played by the churches - especially in confronting
      issues of stigmatisation and abandonment that often accompany patient disclosure,
      and in providing spiritual, emotional and psychological support to patients
      undergoing treatment. 

PMID- 25875065
TI  - Decisions and advice about infant feeding: findings from sociological work in
      KwaZulu-Natal, South Africa.
AB  - What are women's practices and experiences? And what are pregnant women being
      told about risks through breastfeeding in an area of high HIV seroprevalence?
      This work sets out to explore these two principal questions in terms of the
      implications for women, and for international and national policy guidelines on
      infant feeding. During a two-year sociological study in KwaZulu-Natal, semi
      structured questionnaires, individual and group interviews, and an innovative
      storytelling element were used to probe women's decision-making concerning infant
      feeding. In-depth interviews were conducted with different groups of health
      workers, including AIDS counsellors and traditional birth attendants, and
      observations were made at both semi-rural and urban hospitals and clinics. The
      research was carried out at a time when new international and national guidelines
      concerning HIV and infant feeding were being circulated. The research is framed
      within critical and discursive theory, influenced by the work of Foucault, and
      located within a particular feminist theory, concerned with the modes of
      appropriation of 'the sexed body'. The conclusions centre on ethical
      considerations and the rights of women to make informed decisions about their own
      and their baby's health care. Reference is also made to the particular
      socialisation of health workers, especially maternity nurses. The importance of
      the earlier struggle against the unethical practices of multi-nationals is
      recognised, and how this has informed a robust breastfeeding culture. Scant
      attention has been paid to the results of studies undertaken in other African
      locations (mainly West Africa) where key players have introduced infant milk
      formula. The conclusions also engage with the question of the vertical paradigm:
      how women's lives have been caught up in these dilemmas and conflicts in a
      country with a rights' culture. 

PMID- 25875066
TI  - Acceptability of female-controlled HIV/STI prevention options by Nigerian
      professionals - an exploratory study.
AB  - The attitudes of working professionals, particularly in the healthcare sector,
      may play a large role in the acceptance or otherwise of female-controlled HIV/STI
      prevention options. In 2002, we conducted an exploratory study on the perceptions
      surrounding female-controlled HIV/STI prevention options, principally the
      acceptability of a female condom or a vaginal microbicide, among a small sample
      of Nigerian professionals. A self-administered structured questionnaire was given
      to 50 persons representing four professions. The majority of the respondents
      agreed with a proposition stating a need for female-controlled HIV/STI prevention
      options. More females than males supported such options; both male and female
      respondents expressed a higher preference for a vaginal microbicide than for the
      female condom. The reasons given for unwillingness to use the female condom
      included social, cultural and religious biases, cumbersomeness and inefficiency.
      Only a small proportion of the total respondents felt willing to participate in a
      clinical trial with the vaginal microbicide. Further studies are needed to
      determine the relevance of these findings to the professional community in
      Nigeria at large, especially for the purposes of planning better social marketing
      strategies. 

PMID- 25875067
TI  - The Simalelo Peer Education Programme for HIV prevention: a qualitative process
      evaluation of a project in Zambia.
AB  - The aim of the project was to evaluate a peer education programme in Zambia run
      by local people in relation to changes in behaviours, the effects of the
      programme on the community and the dynamics of peer health promotion. A
      qualitative process evaluation using focus groups consisting of both participants
      in the peer education programme and educators was utilised. The peer education
      programme was aimed at setting up anti-AIDS clubs through recreational
      activities, empowering people in a variety of ways, and reaching people in some
      of the most remote parts of the country. Key findings indicate that the programme
      had an impact on participants' attitudes to HIV/AIDS as well as on lifestyle and
      behaviour, both in relation to sexual practices and cultural norms. Knowledge
      about HIV prevention was substantial and clear. Most importantly, the findings
      suggest that success of the programme is related to the fact that it brought the
      community together to fight AIDS. Peer education programmes must be able to
      motivate people to work together with appropriate methods, empower local
      communities and consider issues of long-term sustainability. 

PMID- 25875068
TI  - Knowledge, attitudes and perceptions of HIV/AIDS among traditional birth
      attendants and herbal practitioners in Lagos State, Nigeria.
AB  - Recognising the widespread role of traditional birth attendants (TBAs) and herbal
      practitioners (HPs) in health care at community level in Nigeria, we set out to
      assess their knowledge, attitudes and practices in relation to HIV infection and
      prevention. Questionnaires were administered to a convenience sample of 189
      participants in 20 local government areas of Lagos State. We found that knowledge
      of modes of transmission of HIV was less than adequate and included lack of
      knowledge of the existence of HIV/AIDS amongst some practitioners, claims for the
      ability to treat HIV/AIDS, failure to name major avenues of transmission and
      confusion of HIV/AIDS with other conditions. The use of measures to prevent
      infection of clients and themselves showed that normal standards of infection
      control are not adhered to. Considering that as many as 60% of children born in
      Nigeria are delivered by traditional birth attendants and that use of the
      services of herbal practitioners extends across the entire society in both rural
      and urban settings, this is seen as reason for concern. It is suggested that
      better incorporation of TBAs/HPs into the well-developed primary health care
      system offers not only a way of overcoming the risks of infection posed by
      traditional health practices but also offers an opportunity to extend the reach
      of voluntary counselling and testing and prevention of mother-to-child infection
      programmes. The research has shown the need for appropriate training of TBAs, to
      enable them to recognise the risk of HIV infection in their own practices and to
      encourage them to adopt universal precautions against spreading infection. We
      also recommend that they be more extensively integrated as primary health care
      workers in VCT and PMTCT programmes in Nigeria. We further suggest that referrals
      made between the traditional practitioners and professional health care providers
      can be an effective and successful element of HIV/AIDS prevention and control
      programmes. 

PMID- 25875071
TI  - Experimentally reduced hip-abductor muscle strength and frontal-plane
      biomechanics during walking.
AB  - CONTEXT: Researchers have postulated that reduced hip-abductor muscle strength
      may have a role in the progression of knee osteoarthritis by increasing the
      external knee-adduction moment. However, the relationship between hip-abductor
      strength and frontal-plane biomechanics remains unclear. OBJECTIVE: To
      experimentally reduce hip-abduction strength and observe the subsequent changes
      in frontal-plane biomechanics. DESIGN: Descriptive laboratory study. SETTING:
      Research laboratory. PATIENTS OR OTHER PARTICIPANTS: Eight healthy,
      recreationally active men (age = 27 +/- 6 years, height = 1.75 +/- 0.11 m, mass =
      76.1 +/- 10.0 kg). INTERVENTION(S): All participants underwent a superior gluteal
      nerve block injection to reduce the force output of the hip-abductor muscle
      group. MAIN OUTCOME MEASURE(S): Maximal isometric hip-abduction strength and gait
      biomechanical data were collected before and after the injections. Gait
      biomechanical variables collected during walking consisted of knee- and hip
      adduction moments and impulses and the peak angles of contralateral pelvic drop,
      hip adduction, and ipsilateral trunk lean. RESULTS: Hip-abduction strength was
      reduced after the injection (P = .001) and remained lower than baseline values at
      the completion of the postinjection gait data collection (P = .02). No
      alterations in hip- or knee-adduction moments (hip: P = .11; knee: P = .52) or
      impulses (hip: P = .16; knee: P = .41) were found after the nerve block.
      Similarly, no changes in angular kinematics were observed for contralateral
      pelvic drop (P = .53), ipsilateral trunk lean (P = .78), or hip adduction (P =
      .48). CONCLUSIONS: A short-term reduction in hip-abductor strength was not
      associated with alterations in the frontal-plane gait biomechanics of young,
      healthy men. Further research is needed to determine whether a similar
      relationship is true in older adults with knee osteoarthritis.

PMID- 25875072
TI  - Hierarchical linear model: thinking outside the traditional repeated-measures
      analysis-of-variance box.
AB  - Longitudinal designs are common in the field of athletic training. For example,
      in the Journal of Athletic Training from 2005 through 2010, authors of 52 of the
      218 original research articles used longitudinal designs. In 50 of the 52
      studies, a repeated-measures analysis of variance was used to analyze the data. A
      possible alternative to this approach is the hierarchical linear model, which has
      been readily accepted in other medical fields. In this short report, we
      demonstrate the use of the hierarchical linear model for analyzing data from a
      longitudinal study in athletic training. We discuss the relevant hypotheses,
      model assumptions, analysis procedures, and output from the HLM 7.0 software. We
      also examine the advantages and disadvantages of using the hierarchical linear
      model with repeated measures and repeated-measures analysis of variance for
      longitudinal data. 

PMID- 25875073
TI  - Synthesis of 3-Sulfonylamino Quinolines from 1-(2-Aminophenyl) Propargyl Alcohols
      through a Ag(I)-Catalyzed Hydroamination, (2 + 3) Cycloaddition, and an Unusual
      Strain-Driven Ring Expansion.
AB  - We describe herein a silver-catalyzed conversion of 1-(2-aminophenyl)-propargyl
      alcohols to 4-substituted 3-tosylaminoquinolines using TsN3 as an amino
      surrogate. Controlled reactions reveal the pathway consisting of Ag(I)-catalyzed
      5-exo-dig cyclization, catalyst-free (2 + 3) cycloaddition, and ring-expansive
      rearrangement via nitrogen expulsion. As a support study, we show that the cyclic
      enamines in similar conditions produce amidines via a C-C bond migration. 

PMID- 25875074
TI  - Layer number identification of intrinsic and defective multilayered graphenes up
      to 100 layers by the Raman mode intensity from substrates.
AB  - An SiO2/Si substrate has been widely used to support two-dimensional (2d) flakes
      grown by chemical vapor deposition or prepared by micromechanical cleavage. The
      Raman intensity of the vibration modes of 2d flakes is used to identify the layer
      number of 2d flakes on the SiO2/Si substrate, however, such an intensity is
      usually dependent on the flake quality, crystal orientation and laser
      polarization. Here, we used graphene flakes, a prototype system, to demonstrate
      how to use the intensity ratio between the Si peak from SiO2/Si substrates
      underneath graphene flakes and that from bare SiO2/Si substrates for the layer
      number identification of graphene flakes up to 100 layers. This technique is
      robust, fast and nondestructive against sample orientation, laser excitation and
      the presence of defects in the graphene layers. The effect of relevant
      experimental parameters on the layer-number identification was discussed in
      detail, such as the thickness of the SiO2 layer, laser excitation wavelength and
      numerical aperture of the used objective. This paves the way to use Raman signals
      from dielectric substrates for layer-number identification of ultrathin flakes of
      various 2d materials. 

PMID- 25875075
TI  - A Universal Electron-Transporting/Exciton-Blocking Material for Blue, Green, and
      Red Phosphorescent Organic Light-Emitting Diodes (OLEDs).
AB  - Three m-terphenyl oxadiazole derivatives, 3,3"-bis(5-(pyridin-4-yl)-1,3,4
      oxadiazol-2-yl)-1,1':3',1"-terphenyl (4PyOXD), 3,3"-bis(5-(pyridin-3-yl)-1,3,4
      oxadiazol-2-yl)-1,1':3',1"-terphenyl (3PyOXD), and 3,3"-bis(5-phenyl-1,3,4
      oxadiazol-2-yl)-1,1':3',1"-terphenyl (PhOXD), were synthesized. They exhibit
      relatively high electron mobilities compared with those of known electron
      transport materials such as TAZ, BAlq, and BCP+Alq3. These materials were then
      utilized as electron transporters and hole/exciton blockers for blue, green, and
      red phosphorescent organic light-emitting diodes. The devices exhibited reduced
      driving voltages, very high efficiency, and negligible roll-off. More
      importantly, among these three oxadiazole derivatives, PhOXD performed as an
      ideal electron-transporting material for the blue, green, and red devices with
      excellent external quantum efficiencies (EQEs, >26%) as well as current and power
      efficiencies. Using these materials as an electron-transporting/exciton-blocking
      layer, low roll-off was achieved for the devices, indicative of excellent
      confinement of the triplet excitons in the emitting layer even at high current
      densities. At the normal operation brightness of 1000 cd m(-2), the EQEs remained
      >21.3% for these basic color devices. In addition, the relationships between
      physical properties and structures of the molecules such as the electron
      mobility, triplet energy gap, and efficiency can be clearly rationalized. 

PMID- 25875077
TI  - More DNA-Aptamers for Small Drugs: A Capture-SELEX Coupled with Surface Plasmon
      Resonance and High-Throughput Sequencing.
AB  - To address limitations in the production of DNA aptamers against small molecules,
      we introduce a DNA-based capture-SELEX (systematic evolution of ligands by
      exponential enrichment) protocol with long and continuous randomized library for
      more flexibility, coupled with in-stream direct-specificity monitoring via SPR
      and high throughput sequencing (HTS). Applying this capture-SELEX on tobramycin
      shows that target-specificity arises at cycle number 8, which is confirmed by
      sequence convergence in HTS analysis. Interestingly, HTS also shows that the most
      enriched sequences are already visible after only two capture-SELEX cycles. The
      best aptamers displayed K(D) of approximately 200 nM, similar to RNA and DNA
      based aptamers previously selected for tobramycin. The lowest concentration of
      tobramycin detected on label-free SPR experiments with the selected aptamers is
      20-fold smaller than the clinical range limit, demonstrating suitability for
      small-drug biosensing.

PMID- 25875076
TI  - Cell blebbing upon addition of cryoprotectants: a self-protection mechanism.
AB  - In this work, the mechanism of cell bleb formation upon the addition of
      cryoprotectants (CPAs) was investigated, and the role of cell blebs in protecting
      cells was determined. The results show that after adding CPAs, the hyperosmotic
      stress results in the breakage of the cortical cytoskeleton and the detachment of
      the cell membrane from the cortical cytoskeleton, causing the formation of cell
      blebs. Multiple blebs decrease the intracellular hydrostatic pressure induced by
      the extracellular hyperosmotic shock and alleviate the osmotic damage to cells,
      which reduces the cell mortality rate. In the presence of a low concentration of
      CPAs, cell blebs can effectively protect cells. In contrast, in the presence of a
      high concentration of CPAs, the protective effect is limited because of severe
      disruption in the cortical cytoskeleton. To determine the relationship between
      blebs and the mortality rate of cells, we defined a bleb index and found that the
      bleb index of 0.065 can be regarded as a reference value for the safe addition of
      DMSO to HeLa cells. The bleb index can also explain why the stepwise addition of
      CPAs is better than the single-step addition of CPAs. Moreover, the mechanism of
      the autophagy of cells induced by the hyperosmotic stress was studied, and the
      protective effect associated with the autophagy was compared with the effect of
      the blebbing. The findings reported here elucidate a self-protection mechanism of
      cells experiencing the hyperosmotic stress in the presence of CPAs, and they
      provide significant evidence for cell tolerance in the field of cryopreservation.

PMID- 25875078
TI  - Monocytosis is associated with hemolysis in sickle cell disease.
AB  - BACKGROUND: The clinical relevance of monocytosis in sickle cell disease (SCD) is
      uncertain. The purpose of this study was to explore the association of monocyte
      counts with clinical and laboratory variables in SCD. DESIGN AND METHODS: This
      cross-sectional study was performed using a cohort of adult patients with SCD and
      control subjects without SCD. Complete blood counts, markers of hemolysis,
      coagulation activation, endothelial injury, and other laboratory studies were
      obtained in patients with SCD. Clinical complications were ascertained at the
      time of evaluation and tricuspid regurgitant jet velocity was determined by
      Doppler echocardiography. RESULTS: One hundred and fifty-seven patients with SCD
      and 24 healthy, African-American, control subjects were evaluated. The absolute
      monocyte count was increased in SCD patients compared with healthy controls (0.6
      * 10(9)/l vs. 0.4 * 10(9)/l, P = 0.0025), with higher counts in HbSS/HbSbeta(0)
      thalassemia compared with HbSC/HbSbeta(+) thalassemia. In univariate analyses,
      absolute monocyte count was correlated with reticulocyte count, absolute
      neutrophil count, indirect bilirubin, lactate dehydrogenase, and inversely
      correlated with hemoglobin in SCD patients. Furthermore, monocyte count was
      correlated with soluble vascular cell adhesion molecule-1 (VCAM-1) in
      HbSS/HbSbeta(0) thalassemia patients. No significant associations were observed
      between absolute monocyte count and evaluated clinical complications. In
      multivariable analyses, reticulocyte count and absolute neutrophil count were
      significantly associated with absolute monocyte count. CONCLUSIONS: Monocytosis
      is associated with hemolysis and inflammation in SCD. We suggest that hemolysis
      and the resultant erythropoietic response contribute to monocyte activation.

PMID- 25875079
TI  - The life and significance of Charles Lucas (1713-1771).
AB  - Charles Lucas (1713-1771) was one of the most controversial popular politicians
      to stride the Irish political stage in the eighteenth century. Though the
      descendant of a beneficiary of the Cromwellian plantation, Lucas's personal
      inheritance was small, and he was apprenticed in his teens to an apothecary in
      Dublin. Lucas prospered in that capacity, both as an advocate of higher standards
      within the profession, and as a representative on the lower house (the common
      council) of Dublin Corporation. Predisposed to challenge what he perceived as
      abuses by vested and established interests, Lucas made a name for himself as an
      outspoken critic of the oligarchical pretensions of the lord mayor and aldermen,
      which comprised the upper chamber of the Corporation. His successes were few, but
      he was possessed of a fluent pen, and a precocious awareness that he could best
      communicate with his natural audience through the use of print. As a result, he
      became the darling of an emerging popular political interest, which shared his
      vision of a reformed Protestant constitution. Encouraged by this positive
      response, Lucas offered himself to the electorate of Dublin in 1749, but though
      he campaigned vigorously, and polled well, he was not elected. More consequently
      for Lucas personally, his extension of his critical gaze from the municipality to
      the larger canvas of national and Anglo-Irish politics elicited the hostile
      notice of the most powerful figures in the land, which prompted him to flee the
      country to avoid imprisonment. Lucas was not inactive during his eleven-year
      'exile', but these were comparatively quiet years by comparison with his final
      decade when, following his return to Ireland in 1761, he acquired a national
      profile as MP for Dublin City, a vigorous advocate, and a tireless proponent of
      Patriot policies.

PMID- 25875080
TI  - Early detection for cases of enterovirus- and influenza-like illness through a
      newly established school-based syndromic surveillance system in Taipei, January
      2010 ~ August 2011.
AB  - School children may transmit pathogens with cluster cases occurring on campuses
      and in families. In response to the 2009 influenza A (H1N1) pandemic, Taipei City
      Government officials developed a School-based Infectious Disease Syndromic
      Surveillance System (SID-SSS). Teachers and nurses from preschools to
      universities in all 12 districts within Taipei are required to daily report cases
      of symptomatic children or sick leave requests through the SID-SSS. The pre
      diagnosis at schools is submitted firstly as common pediatric disease syndrome
      groups and re-submitted after confirmation by physicians. We retrieved these data
      from January 2010 to August 2011 for spatio-temporal analysis and evaluated the
      temporal trends with cases obtained from both the Emergency Department-based
      Syndromic Surveillance System (ED-SSS) and the Longitudinal Health Insurance
      Database 2005 (LHID2005). Through the SID-SSS, enterovirus-like illness (EVI) and
      influenza-like illness (ILI) were the two most reported syndrome groups (77.6%
      and 15.8% among a total of 19,334 cases, respectively). The pre-diagnosis
      judgments made by school teachers and nurses showed high consistency with
      physicians' clinical diagnoses for EVI (97.8%) and ILI (98.9%). Most importantly,
      the SID-SSS had better timeliness with earlier peaks of EVI and ILI than those in
      the ED-SSS. Furthermore, both of the syndrome groups in these two surveillance
      systems had the best correlation reaching 0.98 and 0.95, respectively (p<0.01).
      Spatio-temporal analysis observed the patterns of EVI and ILI both diffuse from
      the northern suburban districts to central Taipei, with ILI spreading faster.
      This novel system can identify early suspected cases of two important pediatric
      infections occurring at schools, and clusters from schools/families. It was also
      cost-effective (95.5% of the operation cost reduced and 59.7% processing time
      saved). The timely surveillance of mild EVI and ILI cases integrated with spatial
      analysis may help public health decision-makers with where to target for
      enhancing surveillance and prevention measures to minimize severe cases. 

PMID- 25875081
TI  - Inhibition of cancer cell growth by exposure to a specific time-varying
      electromagnetic field involves T-type calcium channels.
AB  - Electromagnetic field (EMF) exposures affect many biological systems. The
      reproducibility of these effects is related to the intensity, duration,
      frequency, and pattern of the EMF. We have shown that exposure to a specific time
      varying EMF can inhibit the growth of malignant cells. Thomas-EMF is a low
      intensity, frequency-modulated (25-6 Hz) EMF pattern. Daily, 1 h, exposures to
      Thomas-EMF inhibited the growth of malignant cell lines including B16-BL6, MDA-MB
      231, MCF-7, and HeLa cells but did not affect the growth of non-malignant cells.
      Thomas-EMF also inhibited B16-BL6 cell proliferation in vivo. B16-BL6 cells
      implanted in syngeneic C57b mice and exposed daily to Thomas-EMF produced smaller
      tumours than in sham-treated controls. In vitro studies showed that exposure of
      malignant cells to Thomas-EMF for > 15 min promoted Ca(2+) influx which could be
      blocked by inhibitors of voltage-gated T-type Ca(2+) channels. Blocking Ca(2+)
      uptake also blocked Thomas-EMF-dependent inhibition of cell proliferation.
      Exposure to Thomas-EMF delayed cell cycle progression and altered cyclin
      expression consistent with the decrease in cell proliferation. Non-malignant
      cells did not show any EMF-dependent changes in Ca(2+) influx or cell growth.
      These data confirm that exposure to a specific EMF pattern can affect cellular
      processes and that exposure to Thomas-EMF may provide a potential anti-cancer
      therapy.

PMID- 25875082
TI  - A clinical approach to brown adipose tissue in the para-aortic area of the human
      thorax.
AB  - BACKGROUND: Human thoracic brown adipose tissue (BAT), composed of several
      subdivisions, is a well-known target organ of many clinical studies; however, the
      functional contribution of each part of human thoracic BAT remains unknown. The
      present study analyzed the significance of each part of human thoracic BAT in the
      association between regional distribution, cellularity, and factors involved in
      the functional regulation of thoracic BAT. METHODS: We analyzed 1550 healthy
      adults who underwent medical check-ups by positron-emission tomography and
      computed tomography (PET-CT) imaging, 8 cadavers, and 78 autopsy cases in an
      observational study. We first characterized the difference between the
      mediastinum and the supraclavicular areas using counts of BAT detection and
      conditions based on PET-CT outcomes. The measurable important area was then
      subjected to systematic anatomical and immunohistochemical analyses using anti
      uncoupling protein 1 (UCP1) antibody to characterize the cellularity in
      association with age and sex. RESULTS: In PET-CT scanning, the main site of
      thoracic BAT was the mediastinum rather than the supraclavicular area (P < 0.05).
      Systemic macroanatomy revealed that the thumb-sized BAT in the posterior
      mediastinal descending para-aortic area (paBAT) had feeding vessels from the
      posterior intercostal arteries and veins and sympathetic/parasympathetic
      innervation from trunks of the sympathetic and vagus nerves, respectively.
      Immunohistochemical analysis indicated that the paBAT exhibited immunoreactivity
      for tyrosine hydroxylase and vesicular acetylcholine transporter located in the
      pericellular nervous fibers and intracellular UCP1. The brown adipose cells of
      paBAT showed age-dependent decreases in UCP1 expression (P < 0.05), accompanied
      by a significant increase in vacuole formation, indicating fat accumulation (P <
      0.05), from 10 to 37 years of age (P < 0.01). CONCLUSIONS: paBAT may be one of
      the essential sites for clinical application in BAT study because of its visible
      anatomy with feeding vessels and sympathetic/parasympathetic innervation
      functionally affected by outer condition and senescence.

PMID- 25875083
TI  - A high-efficiency HPGe coincidence system for environmental analysis.
AB  - The Comprehensive Nuclear-Test-Ban Treaty (CTBT) is supported by a network of
      certified laboratories which must meet certain sensitivity requirements for CTBT
      relevant radionuclides. At the UK CTBT Radionuclide Laboratory (GBL15), a high
      efficiency, dual-detector gamma spectroscopy system has been developed to improve
      the sensitivity of measurements for treaty compliance, greatly reducing the time
      required for each sample. Utilising list-mode acquisition, each sample can be
      counted once, and processed multiple times to further improve sensitivity. For
      the 8 key radionuclides considered, Minimum Detectable Activities (MDA's) were
      improved by up to 37% in standard mode (when compared to a typical CTBT detector
      system), with the acquisition time required to achieve the CTBT sensitivity
      requirements reduced from 6 days to only 3. When utilising the system in
      coincidence mode, the MDA for (60) Co in a high-activity source was improved by a
      factor of 34 when compared to a standard CTBT detector, and a factor of 17 when
      compared to the dual-detector system operating in standard mode. These MDA
      improvements will allow the accurate and timely quantification of radionuclides
      that decay via both singular and cascade gamma emission, greatly enhancing the
      effectiveness of CTBT laboratories. 

PMID- 25875085
TI  - Correction: Otoliths of five extant species of the annual killifish
      Nothobranchius from the East African Savannah.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0112459.]. 

PMID- 25875084
TI  - Genome-wide analysis of in vivo binding of the master regulator DasR in
      Streptomyces coelicolor identifies novel non-canonical targets.
AB  - Streptomycetes produce a wealth of natural products, including over half of all
      known antibiotics. It was previously demonstrated that N-acetylglucosamine and
      secondary metabolism are closely entwined in streptomycetes. Here we show that
      DNA recognition by the N-acetylglucosamine-responsive regulator DasR is growth
      phase dependent, and that DasR can bind to sites in the S. coelicolor genome that
      have no obvious resemblance to previously identified DasR-responsive elements.
      Thus, the regulon of DasR extends well beyond what was previously predicted and
      includes a large number of genes with functions far removed from N
      acetylglucosamine metabolism, such as genes for small RNAs and DNA transposases.
      Conversely, the DasR regulon during vegetative growth largely correlates to the
      presence of canonical DasR-responsive elements. The changes in DasR binding in
      vivo following N-acetylglucosamine induction were studied in detail and a
      possible molecular mechanism by which the influence of DasR is extended is
      discussed. Discussion of DasR binding was further informed by a parallel
      transcriptome analysis of the respective cultures. Evidence is provided that DasR
      binds directly to the promoters of all genes encoding pathway-specific regulators
      of antibiotic production in S. coelicolor, thereby providing an exquisitely
      simple link between nutritional control and secondary metabolism. 

PMID- 25875086
TI  - Employees' organizational identification and affective organizational commitment:
      an integrative approach.
AB  - Although several studies have empirically supported the distinction between
      organizational identification (OI) and affective commitment (AC), there is still
      disagreement regarding how they are related. Precisely, little attention has been
      given to the direction of causality between these two constructs and as to why
      they have common antecedents and outcomes. This research was designed to fill
      these gaps. Using a cross-lagged panel design with two measurement times, Study 1
      examined the directionality of the relationship between OI and AC, and showed
      that OI is positively related to temporal change in AC, confirming the
      antecedence of OI on AC. Using a cross-sectional design, Study 2 investigated the
      mediating role of OI in the relationship between three work experiences (i.e.,
      perceived organizational support, leader-member exchange, and job autonomy) and
      AC, and found that OI partially mediates the influence of work experiences on AC.
      Finally, Study 3 examined longitudinally how OI and AC combine in the prediction
      of actual turnover, and showed that AC totally mediates the relationship between
      OI and turnover. Overall, these findings suggest that favorable work experiences
      operate via OI to increase employees' AC that, in turn, decreases employee
      turnover. 

PMID- 25875087
TI  - Systematic review of laparoscopic surgery in low- and middle-income countries:
      benefits, challenges, and strategies.
AB  - BACKGROUND: Laparoscopy may prove feasible to address surgical needs in limited
      resource settings. However, no aggregate data exist regarding the role of
      laparoscopy in low- and middle-income countries (LMICs). This study was designed
      to describe the issues facing laparoscopy in LMICs and to aggregate reported
      solutions. METHODS: A search was conducted using Medline, African Index Medicus,
      the Directory of Open Access Journals, and the LILACS/BIREME/SCIELO database.
      Included studies were in English, published after 1992, and reported safety,
      cost, or outcomes of laparoscopy in LMICs. Studies pertaining to arthroscopy,
      ENT, flexible endoscopy, hysteroscopy, cystoscopy, computer-assisted surgery,
      pediatrics, transplantation, and bariatrics were excluded. Qualitative synthesis
      was performed by extracting results that fell into three categories: advantages
      of, challenges to, and adaptations made to implement laparoscopy in LMICs. PRISMA
      guidelines for systematic reviews were followed. RESULTS: A total of 1101
      abstracts were reviewed, and 58 articles were included describing laparoscopy in
      25 LMICs. Laparoscopy is particularly advantageous in LMICs, where there is often
      poor sanitation, limited diagnostic imaging, fewer hospital beds, higher rates of
      hemorrhage, rising rates of trauma, and single income households. Lack of trained
      personnel and equipment were frequently cited challenges. Adaptive strategies
      included mechanical insufflation with room air, syringe suction, homemade
      endoloops, hand-assisted techniques, extracorporeal knot tying, innovative use of
      cheaper instruments, and reuse of disposable instruments. Inexpensive laboratory
      based trainers and telemedicine are effective for training. CONCLUSIONS: LMICs
      face many surgical challenges that require innovation. Laparoscopic surgery may
      be safe, effective, feasible, and cost-effective in LMICs, although it often
      remains limited in its accessibility, acceptability, and quality. This study may
      not capture articles written in languages other than English or in journals not
      indexed by the included databases. Surgeons, policymakers, and manufacturers
      should focus on plans for sustainability, training and retention of providers,
      and regulation of efforts to develop laparoscopy in LMICs.

PMID- 25875088
TI  - Endoscopic retroauricular thyroidectomy: preliminary results.
AB  - BACKGROUND: We sought to seek the potential role of endoscopic thyroidectomy with
      the retroauricular (RA) approach prior to future comparative study with the
      robotic RA thyroidectomy. Therefore, this study aims to verify the surgical
      feasibility of endoscopic RA thyroidectomy. METHODS: Eighteen patients who
      underwent endoscopic RA thyroidectomy for clinically suspicious papillary thyroid
      carcinoma or benign lesions from January to December 2013 were retrospectively
      reviewed and analyzed. RESULTS: All endoscopic operations via RA or modified
      facelift approach were successfully performed, without any significant
      intraoperative complications or conversion to open surgery. Based on patient
      reported outcome questionnaires, all patients were satisfied with their
      postoperative surgical scars. CONCLUSION: Endoscopic RA thyroidectomy is
      technically feasible and safe with satisfactory cosmetic results for patients
      where indicated.

PMID- 25875089
TI  - The surgical stabilization of multiple rib fractures using titanium elastic nail
      in blunt chest trauma with acute respiratory failure.
AB  - BACKGROUND: Blunt chest injuries are usually combined with multiple rib fractures
      and severe lung contusions. This can occasionally induce acute respiratory
      failure and prolong ventilations. In order to reduce the periods of ventilator
      dependency, we propose a less invasive method of fixing multiple rib fractures.
      METHODS: Since October 2009, we have developed a new method to fix fractured ribs
      caused by blunt trauma. Rib fixations were performed using 2.0- or 2.5-mm
      intramedullary titanium elastic nails (TEN), with the help of video-assisted
      thoracoscopic surgery (VATS) and minimal thoracic incisions. All the patients'
      demographics and postoperative data were collected. RESULTS: From January 2010 to
      December 2012, a total of 65 patients presenting with multiple rib fractures
      resulting in acute respiratory failure were included in the study. Twelve
      patients received the new surgical fixation. Rib fixations were performed at an
      average of 4 days after trauma. Patients were successfully weaned off ventilators
      after an average of 3 days. The average length of stay in the hospital and the
      intensive care unit (ICU) was shorter for the patients with fixation than for
      nonsurgical patients. All twelve patients returned to normal daily activities and
      work. CONCLUSIONS: In the reconstruction of an injured chest wall, the VATS with
      TENs fixation in multiple rib fractures is feasible. This method is also
      effective in decreasing the length of the surgical wound. Because the structure
      of the chest cage is protected, the period of mechanical ventilation is shortened
      and the length of stay in the hospital and the ICU can be reduced.

PMID- 25875090
TI  - Comparison of the long-term results of patients who underwent laparoscopy versus
      open distal gastrectomy.
AB  - BACKGROUND: Survival data of patients who underwent laparoscopy assisted distal
      gastrectomy (LADG) compared with those of patients who underwent open distal
      gastrectomy (ODG) for gastric cancer are rarely presented. We compared long-term
      outcomes of LADG with those of ODG in patients with EGC who met the current
      indication for LADG. METHODS: A total of 2410 patients with early gastric cancer
      who underwent curative-intent gastric cancer surgery in three Korean tertiary
      hospitals between January 2003 and June 2009 were included in this multicenter,
      retrospective, propensity-score-matched cohort study. Cox proportional hazard
      regression models were used to evaluate the association between operation methods
      and survival. RESULTS: In the matched cohort, there were no significant
      differences in overall survival [hazard ratio (HR) for the LADG group 0.990; 95%
      confidence interval (CI) 0.675-1.453] or recurrence-free survival (HR 0.989; 95%
      CI 0.480-2.038). The patterns of recurrence were not different between the two
      groups. The most common pattern of recurrence was liver metastasis followed by
      metastasis to distant lymph nodes. The rate of complications in the LADG group
      was higher than that of the ODG group (6.7 vs. 4.6%, P = 0.045). Grade III or
      worse complications that required surgical intervention or were life-threatening
      showed a marginal difference between the two groups (1.7 vs. 2.2%, P = 0.052).
      There were no postoperative mortalities in either group. CONCLUSION: Laparoscopy
      assisted distal gastrectomy for patients with early gastric cancer is feasible in
      terms of the long-term results including survival and recurrence.

PMID- 25875091
TI  - Metabolic and kidney disorders correlate with high atazanavir concentrations in
      HIV-infected patients: is it time to revise atazanavir dosages?
AB  - INTRODUCTION: Ritonavir-boosted atazanavir (ATV/r) is a relatively well tolerated
      antiretroviral drug. However, side effects including hyperbilirubinemia,
      dyslipidemia, nephrolithiasis and cholelithiasis have been reported in the medium
      and long term. Unboosted ATV may be selected for some patients because it has
      fewer gastrointestinal adverse effects, less hyperbilirubinemia and less impact
      on lipid profiles. METHODS: We investigated the distribution of ATV plasma trough
      concentrations according to drug dosage and the potential relationship between
      ATV plasma trough concentrations and drug-related adverse events in a consecutive
      series of 240 HIV-infected patients treated with ATV/r 300/100 mg (68%) or ATV
      400 mg (32%). RESULTS: 43.9% of patients treated with ATV/r 300/100 mg had ATV
      concentrations exceeding the upper therapeutic threshold. A significant and
      direct association has been observed between the severity of hyperbilirubinemia
      and ATV plasma trough concentrations (ATV concentrations: 271 [77-555], 548 [206
      902], 793 [440-1164], 768 [494-1527] and 1491 [1122-1798] ng/mL in patients with
      grade 0, 1, 2, 3 and 4 hyperbilirubinemia, respectively). In an exploratory
      analysis we found that patients with dyslipidemia or nephrolitiasis had ATV
      concentrations significantly higher (582 [266-1148], and 1098 [631-1238] ng/mL,
      respectively) (p<0.001), as compared with patients with no ATV-related
      complications (218 [77-541] ng/mL). CONCLUSIONS: A significant proportion of
      patients treated with the conventional dosage of ATV (300/100) had plasma
      concentrations exceeding the upper therapeutic threshold. These patients that are
      at high risk to experience ATV-related complications may benefit from TDM-driven
      adjustments in ATV dosage with potential advantages in terms of costs and
      toxicity.

PMID- 25875092
TI  - Asymmetric transcript discovery by RNA-seq in C. elegans blastomeres identifies
      neg-1, a gene important for anterior morphogenesis.
AB  - After fertilization but prior to the onset of zygotic transcription, the C.
      elegans zygote cleaves asymmetrically to create the anterior AB and posterior P1
      blastomeres, each of which goes on to generate distinct cell lineages. To
      understand how patterns of RNA inheritance and abundance arise after this first
      asymmetric cell division, we pooled hand-dissected AB and P1 blastomeres and
      performed RNA-seq. Our approach identified over 200 asymmetrically abundant mRNA
      transcripts. We confirmed symmetric or asymmetric abundance patterns for a subset
      of these transcripts using smFISH. smFISH also revealed heterogeneous subcellular
      patterning of the P1-enriched transcripts chs-1 and bpl-1. We screened
      transcripts enriched in a given blastomere for embryonic defects using RNAi. The
      gene neg-1 (F32D1.6) encoded an AB-enriched (anterior) transcript and was
      required for proper morphology of anterior tissues. In addition, analysis of the
      asymmetric transcripts yielded clues regarding the post-transcriptional
      mechanisms that control cellular mRNA abundance during asymmetric cell divisions,
      which are common in developing organisms. 

PMID- 25875093
TI  - AGR3 in breast cancer: prognostic impact and suitable serum-based biomarker for
      early cancer detection.
AB  - Blood-based early detection of breast cancer has recently gained novel momentum,
      as liquid biopsy diagnostics is a fast emerging field. In this study, we aimed to
      identify secreted proteins which are up-regulated both in tumour tissue and serum
      samples of breast cancer patients compared to normal tissue and sera. Based on
      two independent tissue cohorts (n = 75 and n = 229) and one serum cohort (n = 80)
      of human breast cancer and healthy serum samples, we characterised AGR3 as a
      novel potential biomarker both for breast cancer prognosis and early breast
      cancer detection from blood. AGR3 expression in breast tumours is significantly
      associated with oestrogen receptor alpha (P<0.001) and lower tumour grade
      (P<0.01). Interestingly, AGR3 protein expression correlates with unfavourable
      outcome in low (G1) and intermediate (G2) grade breast tumours (multivariate
      hazard ratio: 2.186, 95% CI: 1.008-4.740, P<0.05) indicating an independent
      prognostic impact. In sera analysed by ELISA technique, AGR3 protein
      concentration was significantly (P<0.001) elevated in samples from breast cancer
      patients (n = 40, mainly low stage tumours) compared to healthy controls (n =
      40). To develop a suitable biomarker panel for early breast cancer detection, we
      measured AGR2 protein in human serum samples in parallel. The combined AGR3/AGR2
      biomarker panel achieved a sensitivity of 64.5% and a specificity of 89.5% as
      shown by receiver operating characteristic (ROC) curve statistics. Thus our data
      clearly show the potential usability of AGR3 and AGR2 as biomarkers for blood
      based early detection of human breast cancer. 

PMID- 25875094
TI  - Evidence for chronic low-grade systemic inflammation in individuals with
      agoraphobia from a population-based prospective study.
AB  - BACKGROUND: Anxiety disorders have been linked to an increased risk of incident
      coronary heart disease in which inflammation plays a key pathogenic role. To
      date, no studies have looked at the association between proinflammatory markers
      and agoraphobia. METHODS: In a random Swiss population sample of 2890 persons (35
      67 years, 53% women), we diagnosed a total of 124 individuals (4.3%) with
      agoraphobia using a validated semi-structured psychiatric interview. We also
      assessed socioeconomic status, traditional cardiovascular risk factors (i.e.,
      body mass index, hypertension, blood glucose levels, total cholesterol/high
      density lipoprotein-cholesterol ratio), and health behaviors (i.e., smoking,
      alcohol consumption, and physical activity), and other major psychiatric diseases
      (other anxiety disorders, major depressive disorder, drug dependence) which were
      treated as covariates in linear regression models. Circulating levels of
      inflammatory markers, statistically controlled for the baseline demographic and
      health-related measures, were determined at a mean follow-up of 5.5 +/- 0.4 years
      (range 4.7 - 8.5). RESULTS: Individuals with agoraphobia had significantly higher
      follow-up levels of C-reactive protein (p = 0.007) and tumor-necrosis-factor
      alpha (p = 0.042) as well as lower levels of the cardioprotective marker
      adiponectin (p = 0.032) than their non-agoraphobic counterparts. Follow-up levels
      of interleukin (IL)-1beta and IL-6 did not significantly differ between the two
      groups. CONCLUSIONS: Our results suggest an increase in chronic low-grade
      inflammation in agoraphobia over time. Such a mechanism might link agoraphobia
      with an increased risk of atherosclerosis and coronary heart disease, and needs
      to be tested in longitudinal studies.

PMID- 25875095
TI  - A novel transcriptional factor Nkapl is a germ cell-specific suppressor of Notch
      signaling and is indispensable for spermatogenesis.
AB  - Spermatogenesis is an elaborately regulated system dedicated to the continuous
      production of spermatozoa via the genesis of spermatogonia. In this process, a
      variety of genes are expressed that are relevant to the differentiation of germ
      cells at each stage. Although Notch signaling plays a critical role in germ cell
      development in Drosophila and Caenorhabditis elegans, its function and importance
      for spermatogenesis in mammals is controversial. We report that Nkapl is a novel
      germ cell-specific transcriptional suppressor in Notch signaling. It is also
      associated with several molecules of the Notch corepressor complex such as CIR,
      HDAC3, and CSL. It was expressed robustly in spermatogonia and early
      spermatocytes after the age of 3 weeks. Nkapl-deleted mice showed complete arrest
      at the level of pachytene spermatocytes. In addition, apoptosis was observed in
      this cell type. Overexpression of NKAPL in germline stem cells demonstrated that
      Nkapl induced changes in spermatogonial stem cell (SSC) markers and the reduction
      of differentiation factors through the Notch signaling pathway, whereas testes
      with Nkapl deleted showed inverse changes in those markers and factors.
      Therefore, Nkapl is indispensable because aberrantly elevated Notch signaling has
      negative effects on spermatogenesis, affecting SSC maintenance and
      differentiation factors. Notch signaling should be properly regulated through the
      transcriptional factor Nkapl. 

PMID- 25875096
TI  - 3D evaluation of the lamina cribrosa with swept-source optical coherence
      tomography in normal tension glaucoma.
AB  - PURPOSE: Although the lamina cribrosa (LC) is the primary site of axonal damage
      in glaucoma, adequate methods to image and measure it are currently lacking.
      Here, we describe a noninvasive, in vivo method of evaluating the LC, based on
      swept-source optical coherence tomography (SS-OCT), and determine this method's
      ability to quantify LC thickness. METHODS: This study comprised 54 eyes,
      including normal (n = 18), preperimetric glaucoma (PPG; n = 18), and normal
      tension glaucoma (NTG; n = 18) eyes. We used SS-OCT to obtain 3 x 3 mm cube scans
      of an area centered on the optic disc, and then synchronized reconstructed B- and
      en-face images from this data. We identified the LC in these B-scan images by
      marking the visible borders of the LC pores. We marked points on the anterior and
      posterior borders of the LC in 12 B-scan images in order to create a skeleton
      model of the LC. Finally, we used B-spline interpolation to form a 3D model of
      the LC, including only reliably measured scan areas. We calculated the average LC
      thickness (avgLCT) in this model and used Spearman's rank correlation coefficient
      to compare it with circumpapillary retinal nerve fiber layer thickness (cpRNFLT).
      RESULTS: We found that the correlation coefficient of avgLCT and cpRNFLT was 0.64
      (p < 0.01). The coefficient of variation for avgLCT was 5.1%. AvgLCT differed
      significantly in the groups (normal: 282.6 +/- 20.6 MUm, PPG: 261.4 +/- 15.8 MUm,
      NTG: 232.6 +/- 33.3 MUm). The normal, PPG and NTG groups did not significantly
      differ in age, sex, refractive error or intraocular pressure (IOP), although the
      normal and NTG groups differed significantly in cpRNFLT and Humphrey field
      analyzer measurements of mean deviation. CONCLUSION: Thus, our results indicate
      that the parameters of our newly developed method of measuring LC thickness with
      SS-OCT may provide useful and important data for glaucoma diagnosis and research.

PMID- 25875097
TI  - Reliability and validity of the perfusion, extent, depth, infection and sensation
      (PEDIS) classification system and score in patients with diabetic foot ulcer.
AB  - AIMS: To validate the perfusion, extent, depth, infection and sensation (PEDIS)
      classification system and to make the clinical practice easier, we created a
      score system and compared this system with two previously published common score
      systems. METHODS: A retrospective cohort study was conducted on patients with
      diabetic foot ulcer (DFU) attending our hospital (n=364) from May 2007 to
      September 2013. Participants' characteristics and all variables composing the
      PEDIS classification system were assessed. RESULTS: During a median follow-up of
      25 months (range 6-82), ulcers healed in 217 of the 364 patients (59.6%),
      remained unhealed in 37 patients (10.2%), and were resolved by amputation in 62
      patients (17.0%); 48 patients (13.2%) died. When measured using the PEDIS
      classification system, the outcome of DFU deteriorated with increasing severity
      of each subcategory. Additionally, longer ulcer history, worse perfusion of lower
      limb, a larger extent of the ulcer, a deeper wound, more severe infection, and
      loss of protective sensation were independent predictors of adverse outcome. More
      importantly, the new PEDIS score system showed good diagnostic accuracy,
      especially when compared with the SINBAD and Wagner score systems. CONCLUSIONS:
      The PEDIS classification system, which encompasses relevant variables that
      contribute to the outcome of DFU and has excellent capacity for predicting the
      ulcer outcome, demonstrated acceptable accuracy. The PEDIS classification system
      might be useful in clinical practice and research both for the anticipation of
      health care costs and for comparing patient subgroups.

PMID- 25875098
TI  - Reversible linkage of two distinct small molecule inhibitors of Myc generates a
      dimeric inhibitor with improved potency that is active in myc over-expressing
      cancer cell lines.
AB  - We describe the successful application of a novel approach for generating dimeric
      Myc inhibitors by modifying and reversibly linking two previously described small
      molecules. We synthesized two directed libraries of monomers, each comprised of a
      ligand, a connector, and a bioorthogonal linker element, to identify the optimal
      dimer configuration required to inhibit Myc. We identified combinations of
      monomers, termed self-assembling dimeric inhibitors, which displayed synergistic
      inhibition of Myc-dependent cell growth. We confirmed that these dimeric
      inhibitors directly bind to Myc blocking its interaction with Max and affect
      transcription of MYC dependent genes. Control combinations that are unable to
      form a dimer do not show any synergistic effects in these assays. Collectively,
      these data validate our new approach to generate more potent and selective
      inhibitors of Myc by self-assembly from smaller, lower affinity components. This
      approach provides an opportunity for developing novel therapeutics against Myc
      and other challenging protein:protein interaction (PPI) target classes. 

PMID- 25875099
TI  - Dysfunctional noise cancelling of the rostral anterior cingulate cortex in
      tinnitus patients.
AB  - BACKGROUND: Peripheral auditory deafferentation and central compensation have
      been regarded as the main culprits of tinnitus generation. However, patient-to
      patient discrepancy in the range of the percentage of daytime in which tinnitus
      is perceived (tinnitus awareness percentage, 0 - 100%), is not fully explicable
      only by peripheral deafferentation, considering that the deafferentation is a
      stable persisting phenomenon but tinnitus is intermittently perceived in most
      patients. Consequently, the involvement of a dysfunctional noise cancellation
      mechanism has recently been suggested with regard to the individual differences
      in reported tinnitus awareness. By correlating the tinnitus awareness percentage
      with resting-state source-localized electroencephalography findings, we may be
      able to retrieve the cortical area that is negatively correlated with tinnitus
      awareness percentage, and then the area may be regarded as the core of the noise
      cancelling system that is defective in patients with tinnitus. METHODS AND
      FINDINGS: Using resting-state cortical oscillation, we investigated 80 tinnitus
      patients by correlating the tinnitus awareness percentage with their source
      localized cortical oscillatory activity and functional connectivity. The activity
      of bilateral rostral anterior cingulate cortices (ACCs), left dorsal- and
      pregenual ACCs for the delta band, bilateral rostral/pregenual/subgenual ACCs for
      the theta band, and left rostral/pregenual ACC for the beta 1 band displayed
      significantly negative correlations with tinnitus awareness percentage. Also, the
      connectivity between the left primary auditory cortex (A1) and the rostral ACC,
      as well as between the left A1 and the subgenual ACC for the beta 1 band, were
      negatively correlated with tinnitus awareness percentage. CONCLUSIONS: These
      results may designate the role of the rostral ACC as the core of the descending
      noise cancellation system, and thus dysfunction of the rostral ACC may result in
      perception of tinnitus. The present study also opens a possibility of tinnitus
      modulation by neuromodulatory approaches targeting the rostral ACC.

PMID- 25875100
TI  - Robust vaginal colonization of macaques with a novel vaginally disintegrating
      tablet containing a live biotherapeutic product to prevent HIV infection in
      women.
AB  - MucoCept is a biotherapeutic for prevention of HIV-1 infection in women and
      contains a human, vaginal Lactobacillus jensenii that has been genetically
      enhanced to express the HIV-1 entry inhibitor, modified cyanovirin-N (mCV-N). The
      objective of this study was to develop a solid vaginal dosage form that supports
      sustained vaginal colonization of the MucoCept Lactobacillus at levels previously
      shown, with freshly prepared cultures, to protect macaques from SHIV infection
      and to test this formulation in a macaque vaginal colonization model. Vaginally
      disintegrating tablets were prepared by lyophilizing the formulated bacteria in
      tablet-shaped molds, then packaging in foil pouches with desiccant.
      Disintegration time, potency and stability of the tablets were assessed. For
      colonization, non-synchronized macaques were dosed vaginally with either one
      tablet or five tablets delivered over five days. Vaginal samples were obtained at
      three, 14, and 21 days post-dosing and cultured to determine Lactobacillus
      colonization levels. To confirm identity of the MucoCept Lactobacillus strain,
      genomic DNA was extracted from samples on days 14 and 21 and a strain-specific
      PCR was performed. Supernatants from bacteria were tested for the presence of the
      mCV-N protein by Western blot. The tablets were easy to handle, disintegrated
      within two minutes, potent (5.7x1011 CFU/g), and stable at 4 degrees C and 25
      degrees C. Vaginal administration of the tablets to macaques resulted in
      colonization of the MucoCept Lactobacillus in 66% of macaques at 14 days post
      dosing and 83% after 21 days. There was no significant difference in colonization
      levels for the one or five tablet dosing regimens (p=0.88 Day 14, p=0.99 Day 21).
      Strain-specific PCR confirmed the presence of the bacteria even in culture
      negative macaques. Finally, the presence of mCV-N protein was confirmed by
      Western blot analysis using a specific anti-mCV-N antibody. 

PMID- 25875103
TI  - Job Satisfaction of Nurses in a Regional Hospital in Oman: A Cross-Sectional
      Survey.
AB  - BACKGROUND: Job satisfaction has become a critical issue for healthcare
      organizations, particularly in nursing, because of the shortage of nursing labor,
      the effect on patient care, and the associated costs. This study explores the
      factors that influence the level of job satisfaction of nurses working in one
      regional hospital in Oman. PURPOSE: This study aims to measure the job
      satisfaction of nurses working at a regional hospital in Oman and to determine
      the factors that most significantly influence this satisfaction. Job satisfaction
      is measured using the McCloskey/Mueller Satisfaction Scale. In addition, the
      demographic characteristics of participants (age, gender, level of education,
      years of experience, marital status, work shift, work unit, and nationality) are
      obtained to assess potential correlations. METHODS: A questionnaire survey was
      used to collect the data, and stratified random sampling was used to recruit
      potential participants. A cross-sectional survey was used to collect data from
      155 participants who worked at one regional hospital in Oman, with survey data
      analyzed using SPSS version 19. One hundred forty-three valid responses were
      received (response rate: 92%). The study used descriptive data analysis to
      address the first research question and used analysis methods such as
      multiregression analyses, and one-way analysis of variance to identify the
      relationships between the other variables. RESULTS: The overall mean score for
      satisfaction was 3.49, indicating that participants had a moderate level of job
      satisfaction. "Interaction with coworkers" and "extrinsic reward" earned,
      respectively, the highest and lowest job satisfaction ratings on the subscale of
      McCloskey/Mueller Satisfaction Scale. The results showed that age, work shift,
      and nationality each had a statistically significant effect on overall job
      satisfaction. A multiple regression analysis indicated that 21.8% of the total
      variance in the dependent variables was explained by being non-Omani in
      nationality, indicating that that overall job satisfaction was higher in non
      Omani nurses than in Omani nurses. CONCLUSIONS: The result suggests that
      professional opportunity and extrinsic reward are two important factors that
      affect the job satisfaction of nurses in Oman. Addressing these two factors
      effectively may help improve the quality of nursing care in Oman. Furthermore,
      this study may be conducted more widely in government hospitals in Oman to
      validate the identified factors and to identify additional factors that may
      affect job satisfaction.

PMID- 25875101
TI  - Parasite load induces progressive spleen architecture breakage and impairs
      cytokine mRNA expression in Leishmania infantum-naturally infected dogs.
AB  - Canine Visceral Leishmaniasis (CVL) shares many aspects with the human disease
      and dogs are considered the main urban reservoir of L. infantum in zoonotic VL.
      Infected dogs develop progressive disease with a large clinical spectrum. A
      complex balance between the parasite and the genetic/immunological background of
      the host are decisive for infection evolution and clinical outcome. This study
      comprised 92 Leishmania infected mongrel dogs of various ages from Mato Grosso,
      Brazil. Spleen samples were collected for determining parasite load, humoral
      response, cytokine mRNA expression and histopathology alterations. By real-time
      PCR for the ssrRNA Leishmania gene, two groups were defined; a low (lowP, n = 46)
      and a high parasite load groups (highP, n = 42). When comparing these groups,
      results show variable individual humoral immune response with higher specific IgG
      production in infected animals but with a notable difference in CVL rapid test
      optical densities (DPP) between highP and lowP groups. Splenic architecture
      disruption was characterized by disorganization of white pulp, more evident in
      animals with high parasitism. All cytokine transcripts in spleen were less
      expressed in highP than lowP groups with a large heterogeneous variation in
      response. Individual correlation analysis between cytokine expression and
      parasite load revealed a negative correlation for both pro-inflammatory
      cytokines: IFNgamma, IL-12, IL-6; and anti-inflammatory cytokines: IL-10 and
      TGFbeta. TNF showed the best negative correlation (r2 = 0.231; p<0.001). Herein
      we describe impairment on mRNA cytokine expression in leishmania infected dogs
      with high parasite load associated with a structural modification in the splenic
      lymphoid micro-architecture. We also discuss the possible mechanism responsible
      for the uncontrolled parasite growth and clinical outcome. 

PMID- 25875106
TI  - Human papillomaviruses activate and recruit SMC1 cohesin proteins for the
      differentiation-dependent life cycle through association with CTCF insulators.
AB  - Human papillomaviruses infect stratified epithelia and link their productive life
      cycle to the differentiation state of the host cell. Productive viral replication
      or amplification is restricted to highly differentiated suprabasal cells and is
      dependent on the activation of the ATM DNA damage pathway. The ATM pathway has
      three arms that can act independently of one another. One arm is centered on p53,
      another on CHK2 and a third on SMC1/NBS1 proteins. A role for CHK2 in HPV genome
      amplification has been demonstrated but it was unclear what other factors
      provided important activities. The cohesin protein, SMC1, is necessary for sister
      chromatid association prior to mitosis. In addition the phosphorylated form of
      SMC1 plays a critical role together with NBS1 in the ATM DNA damage response. In
      normal cells, SMC1 becomes phosphorylated in response to radiation, however, in
      HPV positive cells our studies demonstrate that it is constitutively activated.
      Furthermore, pSMC1 is found localized in distinct nuclear foci in complexes with
      gamma-H2AX, and CHK2 and bound to HPV DNA. Importantly, knockdown of SMC1 blocks
      differentiation-dependent genome amplification. pSMC1 forms complexes with the
      insulator transcription factor CTCF and our studies show that these factors bind
      to conserved sequence motifs in the L2 late region of HPV 31. Similar motifs are
      found in most HPV types. Knockdown of CTCF with shRNAs blocks genome
      amplification and mutation of the CTCF binding motifs in the L2 open reading
      frame inhibits stable maintenance of viral episomes in undifferentiated cells as
      well as amplification of genomes upon differentiation. These findings suggest a
      model in which SMC1 factors are constitutively activated in HPV positive cells
      and recruited to viral genomes through complex formation with CTCF to facilitate
      genome amplification. Our findings identify both SMC1 and CTCF as critical
      regulators of the differentiation-dependent life cycle of high-risk human
      papillomaviruses. 

PMID- 25875107
TI  - Comparative transcriptome profiling of the early infection of wheat roots by
      Gaeumannomyces graminis var. tritici.
AB  - Take-all, which is caused by the fungal pathogen, Gaeumannomyces graminis var.
      tritici (Ggt), is an important soil-borne root rot disease of wheat occurring
      worldwide. However, the genetic basis of Ggt pathogenicity remains unclear. In
      this study, transcriptome sequencing for Ggt in axenic culture and Ggt-infected
      wheat roots was performed using Illumina paired-end sequencing. Approximately
      2.62 and 7.76 Gb of clean reads were obtained, and 87% and 63% of the total reads
      were mapped to the Ggt genome for RNA extracted from Ggt in culture and infected
      roots, respectively. A total of 3,258 differentially expressed genes (DEGs) were
      identified with 2,107 (65%) being 2-fold up-regulated and 1,151 (35%) being 2
      fold down-regulated between Ggt in culture and Ggt in infected wheat roots.
      Annotation of these DEGs revealed that many were associated with possible Ggt
      pathogenicity factors, such as genes for guanine nucleotide-binding protein alpha
      2 subunit, cellulase, pectinase, xylanase, glucosidase, aspartic protease and
      gentisate 1, 2-dioxygenase. Twelve DEGs were analyzed for expression by qRT-PCR,
      and could be generally divided into those with high expression only early in
      infection, only late in infection and those that gradually increasing expression
      over time as root rot developed. This indicates that these possible pathogenicity
      factors may play roles during different stages of the interaction, such as
      signaling, plant cell wall degradation and responses to plant defense compounds.
      This is the first study to compare the transcriptomes of Ggt growing
      saprophytically in axenic cultures to it growing parasitically in infected wheat
      roots. As a result, new candidate pathogenicity factors have been identified,
      which can be further examined by gene knock-outs and other methods to assess
      their true role in the ability of Ggt to infect roots. 

PMID- 25875108
TI  - Deletion of histone deacetylase 7 in osteoclasts decreases bone mass in mice by
      interactions with MITF.
AB  - Molecular regulators of osteoclast formation and function are an important area
      of research due to the central role of osteoclasts in bone resorption.
      Transcription factors such as MITF are essential for osteoclast generation by
      regulating expression of the genes required for cellular differentiation and
      resorptive function. We recently reported that histone deacetylase 7 (HDAC7)
      binds to and represses the transcriptional activity of MITF in osteoclasts, and
      that loss of HDAC7 in vitro accelerated osteoclastogenesis. In the current study,
      we extend this initial observation by showing that conditional deletion of HDAC7
      in osteoclasts of mice leads to an in vivo enhancement in osteoclast formation,
      associated with increased bone resorption and lower bone mass. Expression of
      multiple MITF target genes is increased in bone marrow derived osteoclast
      cultures from the HDAC7 knockout mice. Interestingly, multiple regions of the
      HDAC7 amino-terminus can bind to MITF or exert repressive activity. Moreover,
      mutation or deletion of the HDAC7 conserved deacetylase catalytic domain had
      little effect on repressive function. These observations identify HDAC7 in
      osteoclasts as an important molecular regulator of MITF activity and bone
      homeostasis, but also highlight a gap in our understanding of exactly how HDAC7
      functions as a corepressor. 

PMID- 25875110
TI  - Research protocol: a realist synthesis of contestability in community-based
      mental health markets.
AB  - BACKGROUND: In most developed nations, there has been a shift from public
      services to a marketisation of public goods and services - representing a
      significant reform process aiming to transform the way in which community-based
      human services, such as health, are delivered and consumed. For services, this
      means developing the capacity to adapt and innovate in response to changing
      circumstances to achieve quality. The availability of rigorous research to
      demonstrate whether a market approach and contestability, in particular, is a
      coherent reform process is largely absent. Contestability operates on the premise
      that better procurement processes allow more providers to enter the market and
      compete for contracts. This is expected to create stimulus for greater
      efficiencies, innovation and improved service delivery to consumers. There is
      limited understanding, however, about how community-based providers morph and re
      configure in response to the opportunities posed by contestability. This study
      focuses on the effect of a contestability policy on the community-managed mental
      health sector. METHODS/DESIGN: A realist review will be undertaken to understand
      how and why the introduction of contestability into a previously incontestable
      market influences the ways in which community-based mental health providers
      respond to contestability. The review will investigate those circumstances that
      shape organisational response and generate outcomes through activating
      mechanisms. An early scoping has helped to formulate the initial program theory.
      A realist synthesis will be undertaken to identify relevant journal articles and
      grey literature. Data will be extracted in relation to the emerging contextual
      factors, mechanisms and outcomes and their configurations. The analysis will seek
      patterns and regularities in these configurations across the extracted data and
      will focus on addressing our theory-based questions. DISCUSSION: Increasingly,
      community-based mental health markets are moving to contestability models.
      Rigorous research is needed to understand how such markets work and in what
      contexts. The knowledge gained from this study in community-based mental health
      will provide valuable lessons in how contestability works, in what circumstances
      and who benefits when. The results of the proposed research will be useful to
      policy-makers and may be applicable in other contexts beyond the community-based
      mental health sector. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015016808.

PMID- 25875109
TI  - A DNA vaccine against yellow fever virus: development and evaluation.
AB  - Attenuated yellow fever (YF) virus 17D/17DD vaccines are the only available
      protection from YF infection, which remains a significant source of morbidity and
      mortality in the tropical areas of the world. The attenuated YF virus vaccine,
      which is used worldwide, generates both long-lasting neutralizing antibodies and
      strong T-cell responses. However, on rare occasions, this vaccine has toxic side
      effects that can be fatal. This study presents the design of two non-viral DNA
      based antigen formulations and the characterization of their expression and
      immunological properties. The two antigen formulations consist of DNA encoding
      the full-length envelope protein (p/YFE) or the full-length envelope protein
      fused to the lysosomal-associated membrane protein signal, LAMP-1 (pL/YFE), aimed
      at diverting antigen processing/presentation through the major histocompatibility
      complex II precursor compartments. The immune responses triggered by these
      formulations were evaluated in H2b and H2d backgrounds, corresponding to the
      C57Bl/6 and BALB/c mice strains, respectively. Both DNA constructs were able to
      induce very strong T-cell responses of similar magnitude against almost all
      epitopes that are also generated by the YF 17DD vaccine. The pL/YFE formulation
      performed best overall. In addition to the T-cell response, it was also able to
      stimulate high titers of anti-YF neutralizing antibodies comparable to the levels
      elicited by the 17DD vaccine. More importantly, the pL/YFE vaccine conferred 100%
      protection against the YF virus in intracerebrally challenged mice. These results
      indicate that pL/YFE DNA is an excellent vaccine candidate and should be
      considered for further developmental studies. 

PMID- 25875112
TI  - Electrodeposition of germanium at elevated temperatures and pressures from ionic
      liquids.
AB  - The electrodeposition of germanium at elevated temperatures up to 180  degrees C
      and pressures was studied from the ionic liquids 1-butyl-1-methylpyrrolidinium
      dicyanamide and 1-butyl-1-methylpyrrolidinium bis(trifluoromethylsulfonyl)imide
      containing [GeCl4(BuIm)2] (where BuIm = 1-butylimidazole) or GeCl4. Cyclic
      voltammetry (CV), electrochemical quartz crystal microbalance (EQCM), rotating
      ring-disk electrode (RRDE), scanning electron microscope (SEM), X-ray diffraction
      (XRD), transmission electron microscopy (TEM), electron backscatter diffraction
      (EBSD) and Auger electron spectroscopy (AES) were used to investigate the
      electrochemical behavior and the properties of the electrodeposited germanium.
      Electrodeposition at elevated temperatures leads to higher deposition rates due
      to: (1) increase in the diffusion rate of the electroactive germanium compounds;
      (2) faster electrochemical kinetics in the electrolyte; and (3) higher electrical
      conductivity of the electrodeposited germanium film. Moreover, the morphology of
      the germanium film is also of a better quality at higher electrodeposition
      temperatures due to an increase in adatom mobility. 

PMID- 25875111
TI  - A four-compartment metabolomics analysis of the liver, muscle, serum, and urine
      response to polytrauma with hemorrhagic shock following carbohydrate prefeed.
AB  - OBJECTIVE: Hemorrhagic shock accompanied by injury represents a major physiologic
      stress. Fasted animals are often used to study hemorrhagic shock (with injury). A
      fasted state is not guaranteed in the general human population. The objective of
      this study was to determine if fed animals would exhibit a different metabolic
      profile in response to hemorrhagic shock with trauma when compared to fasted
      animals. METHODS: Proton (1H) NMR spectroscopy was used to determine
      concentrations of metabolites from four different compartments (liver, muscle,
      serum, urine) taken at defined time points throughout shock/injury and
      resuscitation. PLS-DA was performed and VIP lists established for baseline, shock
      and resuscitation (10 metabolites for each compartment at each time interval) on
      metabolomics data from surviving animals. RESULTS: Fed status prior to the
      occurrence of hemorrhagic shock with injury alters the metabolic course of this
      trauma and potentially affects mortality. The death rate for CPF animals is
      higher than FS animals (47 vs 28%). The majority of deaths occur post
      resuscitation suggesting reperfusion injury. The metabolomics response to shock
      reflects priorities evident at baseline. FS animals raise the baseline degree of
      proteolysis to provide additional amino acids for energy production while CPF
      animals rely on both glucose and, to a lesser extent, amino acids. During early
      resuscitation levels of metabolites associated with energy production drop,
      suggesting diminished demand. CONCLUSIONS: Feeding status prior to the occurrence
      of hemorrhagic shock with injury alters the metabolic course of this trauma and
      potentially affects mortality. The response to shock reflects metabolic
      priorities at baseline.

PMID- 25875113
TI  - Contribution of temperament to eating disorder symptoms in emerging adulthood:
      Additive and interactive effects.
AB  - Temperament characteristics, such as higher negative emotionality (NE) and lower
      effortful control (EC), are individual difference risk factors for developmental
      psychopathology. Research has also noted relations between temperament and more
      specific manifestations of psychopathology, such as eating disorders (EDs).
      Although work is emerging that indicates that NE and EC may additively contribute
      to risk for ED symptoms, no studies have considered the interactive effects of NE
      and EC in relation to ED symptoms. In the current investigation, we hypothesized
      that (1) low EC would be associated with increased ED symptoms, (2) high NE would
      be associated with increased ED symptoms, and (3) these temperament traits would
      interact, such that the relationship between NE and ED symptoms would be
      strongest in the presence of low EC. After controlling for gender and child
      trauma history, emerging adults' (N=160) lower EC (i.e., more difficulties with
      self-regulation) was associated with more ED symptoms. NE did not emerge as a
      direct predictor of ED symptoms. However, the anticipated interaction of these
      temperament characteristics on ED symptoms was found. The association between NE
      and ED symptoms was only significant in the context of low EC. These findings
      provide evidence that elevated NE may only be a risk factor for the development
      of eating disorders when individuals also have self-regulation difficulties. The
      implications of these findings for research and interventions are discussed. 

PMID- 25875114
TI  - Attachment style and emotional eating in bariatric surgery candidates: The
      mediating role of difficulties in emotion regulation.
AB  - OBJECTIVE: Difficulties with emotion regulation is a hypothesized mechanism
      through which attachment insecurity may affect emotional eating. No studies have
      yet investigated this effect in the bariatric population. Because many obese
      individuals engage in emotional eating, difficulty regulating emotion may be an
      important underlying mechanism through which attachment insecurity is linked to
      emotional eating in bariatric surgery candidates. METHODS: In this cross
      sectional study, 1393 adult bariatric surgery candidates from the Toronto Western
      Hospital were recruited to complete the Emotional Eating Scale (EES), Patient
      Health Questionnaire-9 (PHQ9), Generalized Anxiety Disorder-7 (GAD7),
      Difficulties in Emotion Regulation Scale (DERS), Eating Disorder Examination
      Questionnaire (EDE-Q), and the Experiences for Close Relationships 16-item Scale
      (ECR-16) in order to explore the mediating role of emotion regulation on the
      relationship between attachment insecurity and emotional eating. Path analysis
      within a structural equation modeling framework examined direct and indirect
      effects of attachment insecurity on emotional eating. RESULTS: The indices of
      this overall model indicated that the specified set of direct and indirect
      pathways and corresponding correlations were a good fit with the data (RMSEA<.06,
      CFI=1.00; SRMR<.08). Moreover, tests of all of the possible indirect pathways
      between attachment style and emotional eating were significant. DISCUSSION:
      Findings suggest that difficulties in emotion regulation may be an important
      mechanism to consider when examining the association between attachment
      insecurity and emotional eating in adult bariatric surgery candidates. Although
      causality cannot be concluded, these results shed light on the important role
      that emotion regulation may have in predicting problematic eating in bariatric
      patients.

PMID- 25875115
TI  - Enhanced mucosal immune responses induced by a combined candidate mucosal vaccine
      based on Hepatitis A virus and Hepatitis E virus structural proteins linked to
      tuftsin.
AB  - Hepatitis A virus (HAV) and Hepatitis E virus (HEV) are the most common causes of
      infectious hepatitis. These viruses are spread largely by the fecal-oral route
      and lead to clinically important disease in developing countries. To evaluate the
      potential of targeting hepatitis A and E infection simultaneously, a combined
      mucosal candidate vaccine was developed with the partial open reading frame 2
      (ORF2) sequence (aa 368-607) of HEV (HE-ORF2) and partial virus protein 1 (VP1)
      sequence (aa 1-198) of HAV (HA-VP1), which included the viral neutralization
      epitopes. Tuftsin is an immunostimulatory peptide which can enhance the
      immunogenicity of a protein by targeting it to macrophages and dendritic cells.
      Here, we developed a novel combined protein vaccine by conjugating tuftsin to HE
      ORF2 and HA-VP1 and used synthetic CpG oligodeoxynucleotides (ODNs) as the
      adjuvant. Subsequent experiments in BALB/c mice demonstrated that tuftsin
      enhanced the serum-specific IgG and IgA antibodies against HEV and HAV at the
      intestinal, vaginal and pulmonary interface when delivered intranasally.
      Moreover, mice from the intranasally immunized tuftsin group (HE-ORF2-tuftsin +
      HA-VP1-tuftsin + CpG) showed higher levels of IFN-gamma-secreting splenocytes
      (Th1 response) and ratio of CD4+/CD8+ T cells than those of the no-tuftsin group
      (HE-ORF2 + HA-VP1 + CpG). Thus, the tuftsin group generated stronger humoral and
      cellular immune responses compared with the no-tuftsin group. Moreover, enhanced
      responses to the combined protein vaccine were obtained by intranasal
      immunization compared with intramuscular injection. By integrating HE-ORF2, HA
      VP1 and tuftsin in a vaccine, this study validated an important concept for
      further development of a combined mucosal vaccine against hepatitis A and E
      infection. 

PMID- 25875116
TI  - Subjective and clinically assessed hearing loss; a cross-sectional register-based
      study on a swedish population aged 18 through 50 years.
AB  - OBJECTIVES: Questionnaire studies suggest that hearing is declining among young
      adults. However, few studies have examined the reliability of hearing
      questionnaires among young adult subjects. This study examined the associations
      between pure tone audiometrically assessed (PTA) hearing loss and questionnaire
      responses in young to middle aged adults. MATERIALS AND METHODS: A cross
      sectional study using questionnaire and screening PTA (500 through 6000 Hz) data
      from 15322 Swedish subjects (62% women) aged 18 through 50 years. PTA hearing
      loss was defined as a hearing threshold above 20 dB in both ears at one or more
      frequencies. Data were analysed with chi-square tests, nonlinear regression,
      binary logistic regression, and the generalized estimating equation (GEE)
      approach. RESULTS: The prevalence of PTA hearing loss was 6.0% in men and 2.9% in
      women (p < 0.001). Slight hearing impairment was reported by 18.5% of the men and
      14.8% of the women (p < 0.001), whereas 0.5% of men and women reported very
      impaired hearing. Using multivariate GEE modelling, the odds ratio of PTA hearing
      loss was 30.4 (95% CI, 12.7-72.9) in men and 36.5 (17.2-77.3) in women reporting
      very impaired hearing. The corresponding figures in those reporting slightly
      impaired hearing were 7.06 (5.25-9.49) in men and 8.99 (6.38-12.7) in women.
      These values depended on the sound stimulus frequency (p = 0.001). The area under
      the ROC curve was 0.904 (0.892-0.915) in men and 0.886 (0.872-0.900) in women.
      CONCLUSIONS: Subjective hearing impairment predicted clinically assessed hearing
      loss, suggesting that there is cause for concern as regards the future
      development of hearing in young to middle-aged people.

PMID- 25875117
TI  - Ex vivo cytosolic delivery of functional macromolecules to immune cells.
AB  - Intracellular delivery of biomolecules, such as proteins and siRNAs, into primary
      immune cells, especially resting lymphocytes, is a challenge. Here we describe
      the design and testing of microfluidic intracellular delivery systems that cause
      temporary membrane disruption by rapid mechanical deformation of human and mouse
      immune cells. Dextran, antibody and siRNA delivery performance is measured in
      multiple immune cell types and the approach's potential to engineer cell function
      is demonstrated in HIV infection studies. 

PMID- 25875119
TI  - A green algae mixture of Scenedesmus and Schroederiella attenuates obesity-linked
      metabolic syndrome in rats.
AB  - This study investigated the responses to a green algae mixture of Scenedesmus
      dimorphus and Schroederiella apiculata (SC) containing protein (46.1% of dry
      algae), insoluble fibre (19.6% of dry algae), minerals (3.7% of dry algae) and
      omega-3 fatty acids (2.8% of dry algae) as a dietary intervention in a high
      carbohydrate, high fat diet-induced metabolic syndrome model in four groups of
      male Wistar rats. Two groups were fed with a corn starch diet containing 68%
      carbohydrates as polysaccharides, while the other two groups were fed a diet high
      in simple carbohydrates (fructose and sucrose in food, 25% fructose in drinking
      water, total 68%) and fats (saturated and trans fats from beef tallow, total
      24%). High carbohydrate, high fat-fed rats showed visceral obesity with
      hypertension, insulin resistance, cardiovascular remodelling, and nonalcoholic
      fatty liver disease. SC supplementation (5% of food) lowered total body and
      abdominal fat mass, increased lean mass, and attenuated hypertension, impaired
      glucose and insulin tolerance, endothelial dysfunction, infiltration of
      inflammatory cells into heart and liver, fibrosis, increased cardiac stiffness,
      and nonalcoholic fatty liver disease in the high carbohydrate, high fat diet-fed
      rats. This study suggests that the insoluble fibre or protein in SC helps reverse
      diet-induced metabolic syndrome. 

PMID- 25875118
TI  - Considering maternal dietary modulators for epigenetic regulation and programming
      of the fetal epigenome.
AB  - Fetal life is characterized by a tremendous plasticity and ability to respond to
      various environmental and lifestyle factors, including maternal nutrition.
      Identification of the role of dietary factors that can modulate and reshape the
      cellular epigenome during development, including methyl group donors (e.g.,
      folate, choline) and bioactive compounds (e.g., polyphenols) is of great
      importance; however, there is insufficient knowledge of a particular effect of
      each type of modulator and/or their combination on fetal life. To enhance the
      quality and safety of food products for proper fetal health and disease
      prevention in later life, a better understanding of the underlying mechanisms of
      dietary epigenetic modulators during the critical prenatal period is necessary.
      This review focuses on the influence of maternal dietary components on DNA
      methylation, histone modification, and microRNAs, and summarizes current
      knowledge of the effect and importance of dietary components on epigenetic
      mechanisms that control the proper expression of genetic information. Evidence
      reveals that some components in the maternal diet can directly or indirectly
      affect epigenetic mechanisms. Understanding the underlying mechanisms of how
      early-life nutritional environment affects the epigenome during development is of
      great importance for the successful prevention of adult chronic diseases through
      optimal maternal nutrition. 

PMID- 25875120
TI  - Hydrolysis of the rutinose-conjugates flavonoids rutin and hesperidin by the gut
      microbiota and bifidobacteria.
AB  - Flavonols and flavanones are polyphenols exerting many healthy biological
      activities. They are often glycosylated by rutinose, which hampers absorption in
      the small intestine. Therefore they require the gut microbiota to release the
      aglycone and enable colonic absorption. The role of the gut microbiota and
      bifidobacteria in the release of the aglycones from two major rutinosides,
      hesperidin and rutin, was investigated. In bioconversion experiments, the
      microbiota removed rutinose from both rutin and hesperidin, even though complete
      hydrolysis was not obtained. To investigate whether bifidobacteria can
      participate to the hydrolysis of rutinosides, 33 strains were screened. Rutin was
      resistant to hydrolysis by all the strains. Among six tested species, mostly
      Bifidobacterium catenulatum and Bifidobacterium pseudocatenultum were able to
      hydrolyze hesperidin, by means of a cell-associated activity. This result is in
      agreement with the presence of a putative alpha-l-rhamnosidase in the genome of
      B. pseudocatenulatum, while most of the available genome sequences of
      bifidobacteria aside from this species do not bear this sequence. Even though B.
      pseudocatenulatum may contribute to the release of the aglycone from certain
      rutinose-conjugated polyphenols, such as hesperidin, it remains to be clarified
      whether this species may exert a role in affecting the bioavailability of the
      rutinoside in vivo. 

PMID- 25875121
TI  - The potential benefits of red beetroot supplementation in health and disease.
AB  - In recent years there has been a growing interest in the biological activity of
      red beetroot (Beta vulgaris rubra) and its potential utility as a health
      promoting and disease preventing functional food. As a source of nitrate,
      beetroot ingestion provides a natural means of increasing in vivo nitric oxide
      (NO) availability and has emerged as a potential strategy to prevent and manage
      pathologies associated with diminished NO bioavailability, notably hypertension
      and endothelial function. Beetroot is also being considered as a promising
      therapeutic treatment in a range of clinical pathologies associated with
      oxidative stress and inflammation. Its constituents, most notably the betalain
      pigments, display potent antioxidant, anti-inflammatory and chemo-preventive
      activity in vitro and in vivo. The purpose of this review is to discuss
      beetroot's biological activity and to evaluate evidence from studies that
      specifically investigated the effect of beetroot supplementation on inflammation,
      oxidative stress, cognition and endothelial function. 

PMID- 25875122
TI  - Association between nutritional awareness and diet quality: evidence from the
      observation of cardiovascular risk factors in Luxembourg (ORISCAV-LUX) study.
AB  - This study examined the association between nutritional awareness and diet
      quality, as indicated by energy density, dietary diversity and adequacy to
      achieve dietary recommendations, while considering the potentially important role
      of socioeconomic status (SES). Data were derived from 1351 subjects, aged 18-69
      years and enrolled in the ORISCAV-LUX study. Energy density score (EDS), dietary
      diversity score (DDS) and Recommendation Compliance Index (RCI) were calculated
      based on data derived from a food frequency questionnaire. Nutritional awareness
      was defined as self-perception of the importance assigned to eating balanced
      meals, and classified as high, moderate, or of little importance. Initially, a
      General Linear Model was fit that adjusted for age, sex, country of birth, and
      body mass index (BMI). Furthermore, simultaneous contributions to diet quality of
      individual-level socioeconomic factors, education, and household income were
      examined across levels of nutritional awareness. Attributing high importance was
      associated inversely with energy density (p = 0.02), positively with both dietary
      diversity (p < 0.0001), and adequacy to dietary recommendations (p < 0.0001),
      independent of demographic factors, weight status and SES. Further adjustment for
      household income in the EDS-related multivariable model, reduced the beta
      coefficient by 47% for the "moderate importance" category and 36% for the "high
      importance" category. Likewise, the beta coefficient decreased by 13.6% and 10.7%
      in the DDS-related model, and by 12.5%, and 7.1% in the RCI-related model,
      respectively, across awareness categories. Nutritional awareness has a direct
      effect on diet quality, with a minor component of variance explained by improved
      income. The impact of nutritional awareness on diet quality seems to be a
      promising area for both health promotion and health policy research. 

PMID- 25875123
TI  - Dietary gut microbial metabolites, short-chain fatty acids, and host metabolic
      regulation.
AB  - During feeding, the gut microbiota contributes to the host energy acquisition and
      metabolic regulation thereby influencing the development of metabolic disorders
      such as obesity and diabetes. Short-chain fatty acids (SCFAs) such as acetate,
      butyrate, and propionate, which are produced by gut microbial fermentation of
      dietary fiber, are recognized as essential host energy sources and act as signal
      transduction molecules via G-protein coupled receptors (FFAR2, FFAR3, OLFR78,
      GPR109A) and as epigenetic regulators of gene expression by the inhibition of
      histone deacetylase (HDAC). Recent evidence suggests that dietary fiber and the
      gut microbial-derived SCFAs exert multiple beneficial effects on the host energy
      metabolism not only by improving the intestinal environment, but also by directly
      affecting various host peripheral tissues. In this review, we summarize the roles
      of gut microbial SCFAs in the host energy regulation and present an overview of
      the current understanding of its physiological functions. 

PMID- 25875124
TI  - Glucose regulation and cognitive function after bariatric surgery.
AB  - INTRODUCTION: Obesity is associated with cognitive impairment, and bariatric
      surgery has been shown to improve cognitive functioning. Rapid improvements in
      glycemic control are common after bariatric surgery and likely contribute to
      these cognitive gains. We examined whether improvements in glucose regulation are
      associated with better cognitive function following bariatric surgery. METHOD: A
      total of 85 adult bariatric surgery patients underwent computerized cognitive
      testing and fasting blood draw for glucose, insulin, and glycated hemoglobin
      (HbA1c) at baseline and 12 months postoperatively. RESULTS: Significant
      improvements in both cognitive function and glycemic control were observed among
      patients. After controlling for baseline factors, 12-month homeostatic model
      assessment of insulin resistance HOMA-IR predicted 12-month digits backward (beta
      = -.253, p < .05), switching of attention-A (beta = .156, p < .05), and switching
      of attention-B (beta = -.181, p < .05). Specifically, as HOMA-IR decreased over
      time, working memory, psychomotor speed, and cognitive flexibility improved.
      Decreases in HbA1c were not associated with postoperative cognitive improvements.
      After controlling for baseline cognitive test performance, changes in body mass
      index (BMI) were also not associated with 12-month cognitive function.
      CONCLUSIONS: Small effects of improved glycemic control on improved aspects of
      attention and executive function were observed following bariatric surgery among
      severely obese individuals. Future research is needed to identify the underlying
      mechanisms for the neurocognitive benefits of these procedures.

PMID- 25875126
TI  - Nanoimprint lithography 20 years on.
AB  - To celebrate the 20th anniversary of nanoimprint lithography (NIL) we present a
      perspective of how the technique and its prospects have evolved over the past two
      decades. We describe how it overcame certain fabrication challenges at the time
      it was first reported and look at some of the obstacles that hindered uptake in
      industry initially, as well as likely sectors for future successful commercial
      deployment. Developments in the technique since that are making NIL increasingly
      attractive such as 'moving roll to roll' for higher throughput, are also
      described. 

PMID- 25875125
TI  - The pharmacological and non-pharmacological treatment of attention deficit
      hyperactivity disorder in children and adolescents: protocol for a systematic
      review and network meta-analysis of randomized controlled trials.
AB  - BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is one of the most
      common neurodevelopmental disorders of children and adolescents, with a
      significant impact on health services and the community in terms of economic and
      social burdens. The objective of this systematic review will be to evaluate the
      comparative efficacy and safety of pharmacological and non-pharmacological
      treatments in children and adolescents with ADHD. METHODS: Searches involving
      PubMed/MEDLINE and the Cochrane Database of Systematic Reviews will be used to
      identify related systematic reviews and relevant randomized trials. Search
      results will be supplemented by reports from the regulatory and health technology
      agencies, clinical trials registers and by data requested from trialists and/or
      pharmaceutical companies. We will consider studies evaluating pharmacological
      interventions (e.g. stimulants, non-stimulants, antidepressants), psychological
      interventions (e.g. behavioural interventions, cognitive training and
      neurofeedback) and complementary and alternative medicine interventions (e.g.
      dietary interventions, supplement with fatty acids, vitamins, minerals,
      aminoacids, herbal treatment, homeopathy, and mind-body interventions including
      massage, chiropractic, acupuncture, yoga, meditation, Tai chi). Eligible control
      conditions will be placebo, waitlist, no treatment and usual care. Randomized
      controlled trials of a minimum of 3 weeks duration will be included. The primary
      outcomes of interest will be the proportion of patients who responded to
      treatment and who dropped out of the allocated treatment, respectively. Secondary
      outcomes will include treatment discontinuation due to adverse events, as well as
      the occurrences of serious adverse events and specific adverse events (decreased
      weight, anorexia, insomnia and sleep disturbances, anxiety, syncope and
      cardiovascular events). Two reviewers will independently screen references
      identified by the literature search, as well as potentially relevant full-text
      articles in duplicate. Data will be abstracted and risk of bias will be appraised
      by two team members independently. Conflicts at all levels of screening and
      abstraction will be resolved through discussion. Random-effects pairwise meta
      analyses and Bayesian network meta-analyses will be conducted where appropriate.
      DISCUSSION: This systematic review and network meta-analysis will compare the
      efficacy and safety of treatments used for ADHD in children and adolescents. The
      findings will assist patients, clinicians and healthcare providers to make
      evidence-based decisions regarding treatment selection. SYSTEMATIC REVIEW
      REGISTRATION: PROSPERO CRD42014015008 .

PMID- 25875127
TI  - Tensor GSVD of patient- and platform-matched tumor and normal DNA copy-number
      profiles uncovers chromosome arm-wide patterns of tumor-exclusive platform
      consistent alterations encoding for cell transformation and predicting ovarian
      cancer survival.
AB  - The number of large-scale high-dimensional datasets recording different aspects
      of a single disease is growing, accompanied by a need for frameworks that can
      create one coherent model from multiple tensors of matched columns, e.g.,
      patients and platforms, but independent rows, e.g., probes. We define and prove
      the mathematical properties of a novel tensor generalized singular value
      decomposition (GSVD), which can simultaneously find the similarities and
      dissimilarities, i.e., patterns of varying relative significance, between any two
      such tensors. We demonstrate the tensor GSVD in comparative modeling of patient-
      and platform-matched but probe-independent ovarian serous cystadenocarcinoma (OV)
      tumor, mostly high-grade, and normal DNA copy-number profiles, across each
      chromosome arm, and combination of two arms, separately. The modeling uncovers
      previously unrecognized patterns of tumor-exclusive platform-consistent co
      occurring copy-number alterations (CNAs). We find, first, and validate that each
      of the patterns across only 7p and Xq, and the combination of 6p+12p, is
      correlated with a patient's prognosis, is independent of the tumor's stage, the
      best predictor of OV survival to date, and together with stage makes a better
      predictor than stage alone. Second, these patterns include most known OV
      associated CNAs that map to these chromosome arms, as well as several previously
      unreported, yet frequent focal CNAs. Third, differential mRNA, microRNA, and
      protein expression consistently map to the DNA CNAs. A coherent picture emerges
      for each pattern, suggesting roles for the CNAs in OV pathogenesis and
      personalized therapy. In 6p+12p, deletion of the p21-encoding CDKN1A and p38
      encoding MAPK14 and amplification of RAD51AP1 and KRAS encode for human cell
      transformation, and are correlated with a cell's immortality, and a patient's
      shorter survival time. In 7p, RPA3 deletion and POLD2 amplification are
      correlated with DNA stability, and a longer survival. In Xq, PABPC5 deletion and
      BCAP31 amplification are correlated with a cellular immune response, and a longer
      survival. 

PMID- 25875129
TI  - The impact of Cochrane Reviews: a mixed-methods evaluation of outputs from
      Cochrane Review Groups supported by the National Institute for Health Research.
AB  - BACKGROUND: The last few decades have seen a growing emphasis on evidence
      informed decision-making in health care. Systematic reviews, such as those
      produced by Cochrane, have been a key component of this movement. The National
      Institute for Health Research (NIHR) Systematic Review Programme currently
      supports 20 Cochrane Review Groups (CRGs) in the UK and it is important that this
      funding represents value for money. AIMS AND OBJECTIVES: The overall aim was to
      identify the impacts and likely impacts on health care, patient outcomes and
      value for money of Cochrane Reviews published by 20 NIHR-funded CRGs during the
      years 2007-11. DESIGN: We sent questionnaires to CRGs and review authors,
      undertook interviews with guideline developers (GDs) and used bibliometrics and
      documentary review to get an overview of CRG impact and to evaluate the impact of
      a sample of 60 Cochrane Reviews. The evaluation was guided by a framework with
      four categories (knowledge production, research targeting, informing policy
      development and impact on practice/services). RESULTS: A total of 3187 new and
      updated reviews were published on the Cochrane Database of Systematic Reviews
      between 2007 and 2011, 1502 (47%) of which were produced by the 20 CRGs funded by
      the NIHR. We found 40 examples where reviews appeared to have influenced primary
      research and reviews had contributed to the creation of new knowledge and
      stimulated debate. Twenty-seven of the 60 reviews had 100 or more citations in
      Google ScholarTM (Google, CA, USA). Overall, 483 systematic reviews had been
      cited in 247 sets of guidance. This included 62 sets of international guidance,
      175 sets of national guidance (87 from the UK) and 10 examples of local guidance.
      Evidence from the interviews suggested that Cochrane Reviews often play an
      instrumental role in informing guidance, although reviews being a poor fit with
      guideline scope or methods, reviews being out of date and a lack of communication
      between CRGs and GDs were barriers to their use. Cochrane Reviews appeared to
      have led to a number of benefits to the health service including safer or more
      appropriate use of medication or other health technologies or the identification
      of new effective drugs or treatments. However, whether or not these changes were
      directly as a result of the Cochrane Review and not the result of subsequent
      clinical guidance was difficult to judge. Potential benefits of Cochrane Reviews
      included economic benefits through budget savings or the release of funds,
      improvements in clinical quality, the reduction in the use of unproven or
      unnecessary procedures and improvements in patient and carer experiences.
      CONCLUSIONS: This study identified a number of impacts and likely impacts of
      Cochrane Reviews. The clearest impacts of Cochrane Reviews are on research
      targeting and health-care policy, with less evidence of a direct impact on
      clinical practice and the organisation and delivery of NHS services. Although it
      is important for researchers to consider how they might increase the influence of
      their work, such impacts are difficult to measure. More work is required to
      develop suitable methods for defining and quantifying the impact of research.
      FUNDING: The NIHR Health Technology Assessment programme.

PMID- 25875130
TI  - Demographic factors related to male involvement in reproductive health care
      services in Nigeria.
AB  - OBJECTIVES: Men play a well-recognised role in reproductive health care. They are
      pertinent to the achievement of female reproductive health. This study assessed
      male involvement in reproductive health issues in Nigeria and identified relevant
      factors. METHODS: This was a cross-sectional study of 1530 married men aged 25 to
      45 years selected by a multi-stage sampling procedure. Bivariate and logistic
      regression analyses were performed, with male involvement in reproductive health
      care as the dependent variable. RESULTS: The mean age of the respondents was
      38.64 (+/- 5 SD) years. Although 65.9% of the respondents discussed reproductive
      health issues with their wife, only 39.6% accompanied them during visits to
      clinics. Less than one-third (30.9%) of the respondents were involved in
      reproductive health care. Male involvement in reproductive health care is
      predicted by having completed at least secondary education (OR 4.337; p = 0.007),
      having one or no living child (OR 2.002; p = 0.001), and approval of family
      planning (OR 2.637; p = 0.000). CONCLUSIONS: Male involvement in reproductive
      health care is predicted by level of education, number of living children and
      approval of family planning. There is a need to focus on the identified factors
      in order to strengthen and increase male participation in reproductive health
      care.

PMID- 25875128
TI  - Differential adjuvant activities of TLR7 and TLR9 agonists inversely correlate
      with nitric oxide and PGE2 production.
AB  - Activation of different pattern recognition receptors causes distinct profiles of
      innate immune responses, which in turn dictate the adaptive immune response. We
      found that mice had higher CD4+ T cell expansion to an immunogen, ovalbumin, when
      coadministered with CpG than with CL097 in vivo. To account for this differential
      adjuvanticity, we assessed the activities of CpG and CL097 on antigen-specific
      CD4+ T cell expansion in vitro using an OT-II CD4+ T cell/bone marrow-derived
      dendritic cell (DC) co-culture system. Unexpectedly, ovalbumin-stimulated
      expansion of OT-II CD4+ T cells in vitro was potently suppressed by both TLR
      agonists, with CL097 being stronger than CpG. The suppression was synergistically
      reversed by co-inhibition of cyclooxygenases 1 and 2, and inducible nitric oxide
      (NO) synthase. In addition, stimulation of OT-II CD4+ T cell/DC cultures with
      CL097 induced higher levels of CD4+ T cell death than stimulation with CpG, and
      this CD4+ T cell turnover was reversed by NO and PGE2 inhibition. Consistently,
      the co-cultures stimulated with CL097 produced higher levels of prostaglandin E2
      (PGE2) and NO than stimulation with CpG. CL097 induced higher PGE2 production in
      DC cultures and higher IFN-gamma in the OT-II CD4+ T cell/DC cultures, accounting
      for the high levels of PGE2 and NO. This study demonstrates that the adjuvant
      activities of immunostimulatory molecules may be determined by differential
      induction of negative regulators, including NO and PGE2 suppressing clonal
      expansion and promoting cell death of CD4+ T cells. 

PMID- 25875131
TI  - Effect of Adhesive Strips and Dermal Sutures vs Dermal Sutures Only on Wound
      Closure: A Randomized Clinical Trial.
AB  - IMPORTANCE: Although applying adhesive strips to a wound closure has been shown
      to have outcomes equivalent to those with cuticular suturing, it is unknown
      whether adhesive strips provide additional benefit compared with dermal suturing
      alone. OBJECTIVE: To determine whether the addition of adhesive strips to a wound
      closed with buried interrupted subcuticular sutures improves outcomes following
      wound closure. DESIGN, SETTING, AND PARTICIPANTS: A prospective, randomized split
      wound intervention was conducted between November 14, 2013, and May 16, 2014, in
      patients who underwent cutaneous surgical procedures at the University of
      California, Davis, outpatient dermatology clinic. Fifty-seven patients 18 years
      or older with postoperative defects of at least 3 cm, resulting from either Mohs
      micrographic surgical procedures or surgical excision, were screened for
      participation. Nine patients were excluded and 48 were enrolled. INTERVENTIONS:
      Half of each wound was randomized to receive buried interrupted subcuticular
      sutures and overlying adhesive strips and the other half received buried
      interrupted subcuticular sutures only. MAIN OUTCOMES AND MEASURES: At 3 months'
      follow-up, each patient and 2 blinded observers evaluated the wound using the
      Patient Observer Scar Assessment Scale. RESULTS: The total mean (SD) Patient
      Observer Scar Assessment Scale score for observers for the side that received a
      combination of adhesive strips and buried interrupted subcuticular suturing (12.3
      [4.8]) and the side that received sutures only (12.9 [6.3]) did not differ
      significantly at 3 months (P = .32). There was no significant difference in the
      total patient assessment scale score between the combination closure (14.0 [7.6])
      and sutures only (14.7 [7.6]) sides at 3 months (P = .39). There was also no
      significant difference between the 2 closure methods in terms of mean (SD) scar
      width (both methods: 1.1 [0.8] mm, P = .89) at follow-up. CONCLUSIONS AND
      RELEVANCE: Combination closure with adhesive strips and buried interrupted
      subcuticular suturing was not significantly associated with improved overall scar
      assessment compared with buried interrupted subcuticular suturing alone when
      evaluated by blinded observers or the patients themselves. Our results do not
      support the use of adhesive strips as a means to improve cosmetic outcomes or
      reduce scar width. TRIAL REGISTRATION: clinicaltrials.gov Identifier:
      NCT01979497.

PMID- 25875132
TI  - Patients with type 2 diabetes exhibit cognitive impairment with changes of
      metabolite concentration in the left hippocampus.
AB  - Type 2 diabetes mellitus (T2DM) is associated with cognitive dysfunction.
      Previous studies have reported the relationship between cerebral metabolite
      changes and glucose levels. However, the specific aspects of cognition that are
      affected by metabolic changes in T2DM- related cognitive impairment remain
      undetermined. In this study, 188 T2DM patients and 266 controls were recruited.
      Proton magnetic resonance spectra with a single voxel stimulated echo acquisition
      mode (STEAM) were acquired from the left hippocampus and the frontal lobe.
      Presence of T2DM negatively affected the scores of Mini-Mental State Examination
      (MMSE), sub-tests (i.e., attention and language) of MMSE, Montreal Cognitive
      Assessment (MoCA) according to the Beijing version, and sub-tests (i.e.,
      visuospatial/executive reasoning, attention, and language) of MoCA, rather than
      the Wechsler Memory Scale - Revised in China (WMS-RC), and all memory sub-tests
      contained with the MMSE and MoCA frameworks. T2DM positively affected creatine
      and myoinositol peak areas from the left hippocampus, rather than metabolites in
      the left frontal lobe. Negative correlations were shown between the left
      hippocampal myoinositol levels and language scores, and between the left
      hippocampal creatine levels and visuospatial/executive scores in T2DM. These
      findings suggest that T2DM may be an independent risk factor for cognitive
      impairment. Further, the cognitive domains of visuospatial /executive reasoning,
      attention and language may be predominantly impaired in the early phases of T2DM
      related cognitive impairment. In addition, left hippocampal myoinositol and
      creatine concentrations were associated with cognitive impairment in patients
      with T2DM. 

PMID- 25875134
TI  - In vivo detection of cerebral amyloid fibrils with smart dicynomethylene-4H-pyran
      based fluorescence probe.
AB  - In vivo detection of cerebral beta-amyloid fibrils may facilitate the monitoring
      of beta-amyloidosis in the brain and effectiveness of antiamyloid therapies.
      Thioflavin T (ThT) is a widely used dye for the spectroscopic determination of
      beta-amyloid fibrils, but its ability to detect cerebral beta-amyloid fibrils in
      vivo is limited due to the charged molecule. To this end, a smart dicynomethylene
      4H-pyran (DCM) fluorophore, namely, (E)-2-(2-(4-(dimethylamino)styryl)-6-methyl
      4H-pyran-4-ylidene) malononitrile (PAD-1), was evaluated for in vivo fluorescence
      imaging of cerebral beta-amyloid fibrils. PAD-1 rapidly entered the brain with
      high initial brain uptake after intravenous injection, which is highly desirable
      for in vivo detection of beta-amyloid fibrils. PAD-1 displayed a turn-on effect,
      showing significant enhancement in fluorescence when bound to the aggregated beta
      amyloid fibrils. It also showed specific labeling of beta-amyloid deposits in
      APP/PS1 transgenic mouse brains. Thus, PAD-1 proved to be a valuable alternative
      to ThT for cerebral beta-amyloid detection and may enable quantitative imaging in
      vivo. 

PMID- 25875133
TI  - 'And the best essay is...': Extended contact and cross-group friendships at
      school.
AB  - We conducted one experimental intervention based on extended contact principles
      aimed at fostering the formation of cross-group friendships within educational
      settings. Italian school children took part in a school competition for the best
      essay on personal experiences of cross-group friendships with immigrants, to be
      written in small groups. This manipulation was intended to favour the exchange of
      personal positive cross-group experiences, thus capitalizing on the benefits of
      extended contact. In the control condition, participants wrote an essay on
      friendship, without reference to cross-group relations. Results revealed that
      children who took part in the intervention reported a higher number of outgroup
      friends 3 months later. This indirect effect was sequentially mediated by pro
      contact ingroup and outgroup norms and by outgroup contact behavioural
      intentions. This study provides experimental evidence that interventions based on
      extended contact can foster cross-group friendship formation. Theoretical and
      practical implications of the findings are discussed.

PMID- 25875135
TI  - Controlling interfacial contact and exposed facets for enhancing photocatalysis
      via 2D-2D heterostructures.
AB  - Herein, we report a facile strategy for the creation of 2D layered
      heterostructures with intimate interfacial contact and exposed reactive facets.
      The 2D layered heterostructures with intimate contact by sharing the interfacial
      oxygen atoms and exposed reactive facets endowed the as-prepared BiOIO3/BiOI
      nanostructures with highly enhanced visible photocatalytic performance for NO
      removal. 

PMID- 25875136
TI  - Exposure of Adolescent Mice to Delta-9-Tetrahydrocannabinol Induces Long-Lasting
      Modulation of Pro- and Anti-Inflammatory Cytokines in Hypothalamus and
      Hippocampus Similar to that Observed for Peripheral Macrophages.
AB  - Cannabis use is frequent among adolescents. Its main component, delta-9
      tetrahydrocannabinol (THC), affects the immune system. We recently demonstrated
      that chronic exposure of adolescent mice to THC suppressed immunity immediately
      after treatment but that after a washout period THC induced a long-lasting
      opposite modulation towards a proinflammatory and T-helper-1 phenotype in
      adulthood. The main objective of this study was to investigate whether the same
      effect was also present in brain regions such as the hypothalamus and
      hippocampus. Thirty-three-day-old adolescent and 80-day-old adult male mice were
      used. Acute THC administration induced a similar reduction of macrophage
      proinflammatory cytokines and an IL-10 increase in adult and adolescent mice. THC
      did not affect brain cytokines in adult mice, but a proinflammatory cytokine
      decrease was evident in the adolescent brain. A similar effect was present in the
      hypothalamus and hippocampus after 10 days' THC administration. In contrast, when
      brain cytokines were measured 47 days after the final THC administration, we
      observed an inverted effect in adult mice treated as adolescents, i.e., IL-1beta
      and TNF-alpha increased and IL-10 decreased, indicating a shift toward
      neuroinflammation. These data suggest that THC exposure in adolescence has long
      lasting effects on brain cytokines that parallel those present in the periphery.
      This modulation may affect vulnerability to immune and behavioural diseases in
      adulthood. 

PMID- 25875138
TI  - Species sensitivity distributions for engineered nanomaterials.
AB  - Engineered nanomaterials (ENMs) are a relatively new strain of materials for
      which little is understood about their impacts. A species sensitivity
      distribution (SSDs) is a cumulative probability distribution of a chemical's
      toxicity measurements obtained from single-species bioassays of various species
      that can be used to estimate the ecotoxicological impacts of a chemical. The
      recent increase in the availability of acute toxicity data for ENMs enabled the
      construction of 10 ENM-specific SSDs, with which we analyzed (1) the range of
      toxic concentrations, (2) whether ENMs cause greater hazard to an ecosystem than
      the ionic or bulk form, and (3) the key parameters that affect variability in
      toxicity. The resulting estimates for hazardous concentrations at which 5% of
      species will be harmed ranged from <1 ug/L for PVP-coated n-Ag to >3.5 mg/L for
      CNTs. The results indicated that size, formulation, and the presence of a coating
      can alter toxicity, and thereby corresponding SSDs. Few statistical differences
      were observed between SSDs of an ENM and its ionic counterpart. However, we did
      find a significant correlation between the solubility of ENMs and corresponding
      SSD. Uncertainty in SSD values can be reduced through greater consideration of
      ENM characteristics and physiochemical transformations in the environment. 

PMID- 25875137
TI  - Psychiatric Symptoms, Salivary Cortisol and Cytokine Levels in Young Marijuana
      Users.
AB  - Psychological maturation continues into young adulthood when substance abuse and
      several psychiatric disorders often emerge. Marijuana is the most common illicit
      drug abused by youths, typically preceding other illicit substances. We aimed to
      evaluate the complex and poorly studied relationships between marijuana use,
      psychiatric symptoms, and cortisol levels in young marijuana users. Psychiatric
      symptoms and salivary cortisol were measured in 122 youths (13-23 years old) with
      and without marijuana use. Psychiatric symptoms were evaluated using the Symptom
      Checklist-90-R and Brief Psychiatric Rating Scale. Mid-day salivary cortisol
      levels were measured. Additionally, salivary cytokine levels were measured in a
      subset of participants. Although the cortisol levels and salivary cytokine levels
      were similar, the young marijuana users had more self-reported and clinician
      rated psychiatric symptoms than controls, especially anxiety-associated symptoms.
      Moreover, marijuana users with earlier age of first use had more symptoms, while
      those with longer abstinence had fewer symptoms. Greater cumulative lifetime
      marijuana use was also associated with greater psychiatric symptoms. The
      discordant anxiety (feeling stressed or anxious despite normal cortisol) in the
      marijuana users, as well as symptom exacerbations with early and continued
      marijuana use in young marijuana users suggest that marijuana use may contribute
      to an aberrant relationship between stress response and psychiatric symptoms. The
      greater symptomatology, especially in those with earlier initiation and greater
      marijuana usage, emphasize the need to intervene for substance use and perceived
      anxiety in this population. 

PMID- 25875139
TI  - Largely enhanced saturable absorption of a complex of plasmonic and molecular
      like au nanocrystals.
AB  - A saturable absorber is a nonlinear functional material widely used in laser and
      photonic nanodevices. Metallic nanostructures have prominent saturable absorption
      (SA) at the plasmon resonance frequency owing to largely enhanced ground state
      absorption. However, the SA of plasmonic metal nanostructures is hampered by
      excited-state absorption processes at very high excitation power, which usually
      leads to a changeover from SA to reversed SA (SA->RSA). Here, we demonstrate
      tunable nonlinear absorption behaviours of a nanocomplex of plasmonic and
      molecular-like Au nanocrystals. The SA->RSA process is efficiently suppressed,
      and the stepwise SA->SA process is fulfilled owing to energy transfer in the
      nanocomplex. Our observations offer a strategy for preparation of the saturable
      absorber complex and have prospective applications in liquid lasers as well as
      one-photon nonlinear nanodevices. 

PMID- 25875141
TI  - Knowledge, attitudes and sexual practices of adolescents with mild retardation,
      in relation HIV/AIDS.
AB  - This study investigates the knowledge, attitudes and sexual practices of
      adolescents with mild mental retardation (MMR) in relation to HIV/AIDS.
      Questionnaires were personally administered to a saturation sample of 90
      adolescents with MMR drawn from one specialised educational institution in
      Durban, South Africa. The study revealed critical gaps and erroneous beliefs
      regarding knowledge of HIV/AIDS, especially with regard to its existence,
      transmission and cure. Participants indicated a high degree of exposure to
      various sources of information, particularly media messages. The results indicate
      that gender-role prescriptions and prevailing social constructions of immorality
      have had a negative influence on the attitudes and behaviour of participants,
      particularly with regard to sexual practices and preventative risk behaviours.
      Furthermore, the sample was found to have low levels of self-efficacy in relation
      to sexual negotiation and decision-making, more specifically with regard to
      condom use. It should be noted, however, that only a small proportion of the
      sample was sexually active and the use of contraceptives was accordingly found to
      be extremely low. The findings are discussed against the backdrop of the
      empirical literature on HIV/AIDS, developmental theory, and pertinent theories
      and models of health behaviour. This study may help to promote a better
      understanding of the psycho-educational dynamics of HIV infection in this special
      group of adolescents, and also help to inform attempts to tailor suitable
      educational programmes, as well as promote further research to add to our
      knowledge as we address the problems of HIV/AIDS among this group. 

PMID- 25875142
TI  - Vaccine preparedness: lessons from Lyantonde, Uganda.
AB  - To explore how to better educate rural Africans about preventive HIV/AIDS vaccine
      trials, 15 semi-structured, open-ended interviews were conducted with villagers
      in Lyantonde, Rakai District, Uganda. This study reports on the findings by
      focusing on the attitudes, knowledge and questions the rural villagers had about
      HIV/AIDS-preventive vaccine testing. While several interviewees confused
      preventive vaccines with therapeutic vaccines, most were clear about the
      distinction and about key questions to ask about vaccine testing. In addition,
      some subjects manifested high levels of trust in the likely effectiveness of
      preventive vaccines, even in the testing stages, most subjects demonstrated the
      potential to be intelligently inquisitive about the likely effects. In sum, these
      villagers show the potential to be reliable subjects, motivated for appropriate
      reasons, and willing to play a role in advancing the progress of HIV/AIDS vaccine
      development in Africa. 

PMID- 25875140
TI  - Reconstructing and mining the B cell repertoire with ImmunediveRsity.
AB  - The B cell antigen receptor repertoire is highly diverse and constantly modified
      by clonal selection. High-throughput DNA sequencing (HTS) of the lymphocyte
      repertoire (Rep-Seq) represents a promising technology to explore such diversity
      ex-vivo and assist in the identification of antigen-specific antibodies based on
      molecular signatures of clonal selection. Therefore, integrative tools for
      repertoire reconstruction and analysis from antibody sequences are needed. We
      developed ImmunediveRity, a stand-alone pipeline primarily based in R programming
      for the integral analysis of B cell repertoire data generated by HTS. The
      pipeline integrates GNU software and in house scripts to perform quality
      filtering, sequencing noise correction and repertoire reconstruction based on V,
      D and J segment assignment, clonal origin and unique heavy chain identification.
      Post-analysis scripts generate a wealth of repertoire metrics that in conjunction
      with a rich graphical output facilitates sample comparison and repertoire mining.
      Its performance was tested with raw and curated human and mouse 454-Roche
      sequencing benchmarks providing good approximations of repertoire structure.
      Furthermore, ImmunediveRsity was used to mine the B cell repertoire of immunized
      mice with a model antigen, allowing the identification of previously validated
      antigen-specific antibodies, and revealing different and unexpected clonal
      diversity patterns in the post-immunization IgM and IgG compartments. Although
      ImmunediveRsity is similar to other recently developed tools, it offers
      significant advantages that facilitate repertoire analysis and repertoire mining.
      ImmunediveRsity is open source and free for academic purposes and it runs on 64
      bit GNU/Linux and MacOS. Available at:
      https://bitbucket.org/ImmunediveRsity/immunediversity/.

PMID- 25875143
TI  - HIV disclosure and other factors that impact on adherence to antiretroviral
      therapy: the case of Soweto, South Africa.
AB  - Some authors argue that there are no predictors of adherence to medication, while
      others proffer indicators of likely adherence. These contextual factors are wide
      ranging and may be interdependent. There are few studies of adherence in resource
      poor settings. Of these, many were linked to particular trials whose conditions
      were highly controlled. For instance, the number of participants in the trial was
      small, the participants were strictly selected and they were offered much
      adherence support. These conditions will largely fall away with wider access to
      antiretroviral drugs (ARVs) such as South Africa is undertaking. Poor adherence
      remains one of the challenges to scaling-up access to ARVs, and, as such, the
      likely barriers to adherence need to be understood and countered. This study
      explores contextual factors - such as disclosure, preparation for treatment,
      treatment meaning and treatment acceptance - as aspects of lifestyle that can
      bear on adherence. Those who had disclosed were largely supported at household
      level, and after initial problems with adherence, participants adjusted and were
      able to include ARV treatment in their daily repertoire. Although the
      anticipation of stigma remains an obstacle to wide disclosure, antiretroviral
      therapy offers new hope and has the potential to impact on stigma. 

PMID- 25875144
TI  - Relationships, partnerships and politics in the lives of the urban poor in AIDS
      afflicted Swaziland.
AB  - This paper seeks to better understand how poor urban families caring for children
      are able to access help from beyond the kinship group in a setting where HIV
      prevalence has risen to over 40%. The fieldwork shows that livelihoods were
      affected by multiple shocks and families were struggling to provide education,
      health care, clothing and food for all children in their care. Orphan status or
      gender did not appear to affect children's access to education. Families turned
      to neighbours, churches and the work place for assistance. Neighbours varied in
      their response and were rarely able to give material assistance. Churches were
      seen solely as sources of emotional and spiritual support. Work-place
      relationships provided material as well as emotional support. Government and NGO
      assistance was limited and poorly coordinated at the beginning of the fieldwork
      and criteria for selection was unclear to many respondents. Some respondents felt
      marginalised from community structures. Using respondents' experiences when
      trying to access education and health care, the author illustrates the importance
      of the quality of relationships and partnerships at all levels (international,
      national and local) as well as the need for more synergy between top-down and
      bottom-up approaches. A much stronger coordinating role for government officials
      and the development of public welfare support are seen as critical to alleviate
      the poverty in which AIDS thrives. 

PMID- 25875145
TI  - Does conflict increase vulnerability to HIV infection? Issues for a research
      agenda.
AB  - Much action has been taken in the last ten years to prevent and mitigate HIV
      infection in times of conflict, yet two fundamental questions remain unanswered:
      Does conflict always and everywhere increase vulnerability to HIV infection, and
      are women and girls always disproportionately affected? This paper considers the
      ways in which conflict, gender inequality and HIV prevalence and infection rates
      may or may not be connected; its intention is to map key areas for a research
      agenda addressing issues of HIV/AIDS, gender and conflict. Consideration is also
      given to how HIV prevention and mitigation activities in times of conflict,
      transition, and the post-conflict reconstruction and development phase might best
      serve vulnerable populations. In the worst instance, failure to achieve some
      consensus on the best way forward might contribute to reduced attention by the
      international community and donors to civilian populations' vulnerability to HIV
      infection during times of conflict. 

PMID- 25875146
TI  - Human rights and access to AIDS treatment in Mozambique.
AB  - This article explores key issues related to the agitation for human rights in
      Mozambique and its weak performance power. I define human rights in the context
      of HIV/AIDS as well as rights-based approaches to development and health. Based
      on fieldwork, I describe and analyse how human rights are received and applied in
      HIV/AIDS organisations in Mozambique. The central argument is that the weak
      performance power of human rights can be explained by the absence of their
      invocation, social-influence ability and social agitation, with reference made to
      Sen's (2004) theory of human rights. The article compares original findings to a
      rights-based approach to AIDS treatment in South Africa reported by Jones (2005).
      I argue that the successful agitation of human rights depends on skilful
      appropriation of a rights discourse adapted to the unique social and cultural
      context of Mozambique. Finally, the theory of transnational governmentality by
      Ferguson & Gupta (2002) is used to illustrate the challenges posed to an
      ethnography of human rights in an environment in which civil society and
      international organisations are simultaneously in alliance with and in opposition
      to the government. 

PMID- 25875147
TI  - Is khat-chewing associated with HIV risk behaviour? A community-based study from
      Ethiopia.
AB  - This study examines the possible association between the stimulant khat and risky
      sexual behaviour that might aggravate the spread of HIV. A community-based cross
      sectional survey involving 4 000 individuals and focus group discussions were
      conducted to assess the attitudes and perceptions of an Ethiopian population
      towards the habit of khat-chewing and its possible association with risky sexual
      behaviour. All participants in the focus group discussions and 38% of the survey
      respondents were of the opinion that behaviours associated with the mild narcotic
      effects of khat are conducive to casual sex, and hence constitute an increased
      risk for contracting and spreading HIV. A significant shift towards casual sex
      practices was observed in response to the effects induced by the substance, and a
      strong association was observed between khat-chewing, indulgence in alcohol and
      recourse to risky sexual behaviours. There was no significant difference in the
      use or non-use of condoms among those male chewers who admitted resorting to
      casual sex after khat-chewing. We suggest that HIV/AIDS programmes in certain
      regions should address the habitual use of khat and other substances of potential
      abuse as part of their intervention efforts to curb the epidemic. 

PMID- 25875148
TI  - Psychosocial disadvantage: preparation, grieving, remembrance and recovery for
      orphans in eastern Zimbabwe.
AB  - Few programmes for sub-Saharan Africa's 12.3 million children orphaned by AIDS
      have focused on their high risk for psychosocial problems. As groundwork for
      supporting orphans' healthy development, this study describes the preparation,
      grief, and memorial experiences and the physical and psychosocial well-being of
      144 double orphans and 109 single orphans in rural eastern Zimbabwe. Most
      received no preparation or orphan-specific support for mourning and emotional
      recovery. On measures of physical and psychosocial well-being, orphans did more
      poorly than 87 non-orphaned classmates, perhaps reflecting the combined
      interaction of economic disadvantage and orphan status. Financial hardship was
      most severe among single orphans. Double orphans' responses suggested perceptions
      of isolation, lack of support and personal difference. Distress was greatest
      among younger orphans (<13 years). Given the importance of emotional health to
      child and societal development, scaled-up financial assistance should incorporate
      programmes to help children prepare for and recover from the loss of their
      parents. 

PMID- 25875149
TI  - Disability grants or antiretrovirals? A quandary for people with HIV/AIDS in
      South Africa.
AB  - According to the Department of Social Development, disability grants are
      available to adult South African citizens and permanent residents who are
      incapacitated and unable to work due to illness or disability. A number of people
      living with HIV/AIDS (PWAs) have accessed disability grants once they have
      fulfilled the criteria set down by the Department of Social Development. Current
      government policies entitle PWAs, a least in theory, to access antiretroviral
      medications. Where PWAs have been able to access antiretroviral treatment (ART)
      through the government's antiretroviral programme, this has led to an improvement
      in their health and subsequent disqualification for a disability grant. In South
      Africa's highly unequal society, the disability grant often operates as the only
      source of income for poor families. This has created an untenable situation as
      many PWAs are forced to choose between receiving their disability grant and
      accessing life-saving medication. We explore the intersection of social security
      with access to ART and argue that it presents complex problems in the context of
      HIV/AIDS, and thus requires urgent debate and resolution. Potential solutions to
      this problem, including the provision of a basic income grant to all South
      Africans, are proposed. 

PMID- 25875150
TI  - Evidence for the effects of yogurt on gut health and obesity.
AB  - Obesity is associated with increased risk for chronic diseases, and affects both
      developed and developing nations. Yogurt is a nutrient-dense food that may
      benefit individuals with lactose intolerance, constipation and diarrheal
      diseases, hypertension, cardiovascular diseases, diabetes, and certain types of
      cancer. Emerging evidence suggests that yogurt consumption might also improve the
      health of obese individuals. Obesity is often accompanied by chronic, low-grade
      inflammation perpetuated by adipose tissue and the gut. In the gut, obesity
      associated dysregulation of microbiota and impaired gut barrier function may
      increase endotoxin exposure. Intestinal barrier function can be compromised by
      pathogens, inflammatory cytokines, endocannabinoids, diet, exercise, and
      gastrointestinal peptides. Yogurt consumption may improve gut health and reduce
      chronic inflammation by enhancing innate and adaptive immune responses,
      intestinal barrier function, lipid profiles, and by regulating appetite. While
      this evidence suggests that yogurt consumption is beneficial for obese
      individuals, randomized-controlled trials are needed to further support this
      hypothesis.

PMID- 25875151
TI  - Laparoscopic surgery for colorectal cancer is not associated with an increase in
      the circulating levels of several inflammation-related factors.
AB  - It has been hypothesized that inflammatory response triggered by surgery might
      induce the release of molecules that could promote proliferation, invasion and
      metastasis of surviving cancer cells. To test this hypothesis, the levels of
      multiple inflammation-related circulating factors were analyzed in patients
      undergoing surgery for colorectal cancer. A Luminex xMAP system was used to
      simultaneously assess levels of IL-1beta, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7,
      IL-8, IL-9, IL-10, IL-12, IL-13, IL-15, IL-17, FGF, eotaxin, G-CSF, GM-CSF, IFN
      gamma, IP-10, MCP-1, MIP-1alpha, MIP-1beta, PDGF-BB, RANTES, TNF-alpha and VEGF
      in 20 colorectal cancer patients and 10 age-matched non-neoplastic patients. In
      cancer patients analyses were performed at baseline (before surgery) and at
      different time points (up to 30 days) following laparoscopic surgery.
      Significantly higher levels of IL-1beta, IL-7, IL-8, G-CSF, IFN-gamma and TNF
      alpha were detected in colorectal cancer patients compared to controls at
      baseline. In colorectal cancer patients, circulating levels decreased
      progressively following surgery and after day 30 post-surgery were no longer
      different from controls. These findings suggest that expression levels of several
      cytokines are higher in colorectal cancer patients compared to control subjects
      and no significant increase in several inflammation-related circulating factors
      is observed following laparoscopic surgery for cancer. Confirmation and
      validation in a different and larger cohort of patients are warranted. 

PMID- 25875152
TI  - Toward the Selective Inhibition of G Proteins: Total Synthesis of a Simplified YM
      254890 Analog.
AB  - A simplified analog (WU-07047) of the selective Galphaq/11 inhibitor YM-254890
      has been synthesized, and an initial probe of its activity conducted. In the
      analog, the two peptide-based linkers in the cyclic YM-254890 have been replaced
      with hydrocarbon chains. This enables a convergent approach to the synthesis of
      the analog. Biochemical assays showed that while the simplified analog is not as
      potent as YM-254890, it does still inhibit Gq. 

PMID- 25875153
TI  - Nitrogen and phosphorus co-doped graphene quantum dots: synthesis from adenosine
      triphosphate, optical properties, and cellular imaging.
AB  - Graphene quantum dots (GQDs) are emerging zero-dimensional materials promising a
      wide spectrum of applications, particularly, as superior fluorescent reporters
      for bio-imaging and optical sensing. Heteroatom doping can endow GQDs with new or
      improved photoluminescence properties. Here, we demonstrate a simple strategy for
      the synthesis of nitrogen and phosphorus co-doped GQDs from a single biomolecule
      precursor (adenosine triphosphate - ATP). Such ATP-GQDs exhibit high fluorescence
      quantum yield, strong two-photon upconversion, small molecular weight, high
      photostability, and good biocompatibility. Furthermore, transferrin conjugated
      ATP-GQDs have been used for imaging and real-time tracking of transferrin
      receptors in live cells. 

PMID- 25875154
TI  - Quantum dots based mesoporous structured imprinting microspheres for the
      sensitive fluorescent detection of phycocyanin.
AB  - Phycocyanin with important physiological/environmental significance has attracted
      increasing attention; versatile molecularly imprinted polymers (MIPs) have been
      applied to diverse species, but protein imprinting is still quite difficult.
      Herein, using phycocyanin as template via a sol-gel process, we developed a novel
      fluorescent probe for specific recognition and sensitive detection of phycocyanin
      by quantum dots (QDs) based mesoporous structured imprinting microspheres
      (SiO2@QDs@ms-MIPs), obeying electron-transfer-induced fluorescence quenching
      mechanism. When phycocyanin was present, a Meisenheimer complex would be produced
      between phycocyanin and primary amino groups of QDs surface, and then the
      photoluminescent energy of QDs would be transferred to the complex, leading to
      the fluorescence quenching of QDs. As a result, the fluorescent intensity of the
      SiO2@QDs@ms-MIPs was significantly decreased within 8 min, and accordingly a
      favorable linearity within 0.02-0.8 MUM and a high detectability of 5.9 nM were
      presented. Excellent recognition specificity for phycocyanin over its analogues
      was displayed, with a high imprinting factor of 4.72. Furthermore, the validated
      probe strategy was successfully applied to seawater and lake water sample
      analysis, and high recoveries in the range of 94.0-105.0% were attained at three
      spiking levels of phycocyanin, with precisions below 5.3%. The study provided
      promising perspectives to develop fluorescent probes for convenient, rapid
      recognition and sensitive detection of trace proteins from complex matrices, and
      further pushed forward protein imprinting research. 

PMID- 25875155
TI  - An Investigation of Operational Decision Making in Situ: Incident Command in the
      U.K. Fire and Rescue Service.
AB  - OBJECTIVE: The aim of this study was to better understand the nature of decision
      making at operational incidents in order to inform operational guidance and
      training. BACKGROUND: Normative models of decision making have been adopted in
      the guidance and training for emergency services. In these models, it is assumed
      that decision makers assess the current situation, formulate plans, and then
      execute the plans. However, our understanding of how decision making unfolds at
      operational incidents remains limited. METHOD: Incident commanders, attending 33
      incidents across six U.K. Fire and Rescue Services, were fitted with helmet
      mounted cameras, and the resulting video footage was later independently coded
      and used to prompt participants to provide a running commentary concerning their
      decisions. RESULTS: The analysis revealed that assessment of the operational
      situation was most often followed by plan execution rather than plan formulation,
      and there was little evidence of prospection about the potential consequences of
      actions. This pattern of results was consistent across different types of
      incident, characterized by level of risk and time pressure, but was affected by
      the operational experience of the participants. CONCLUSION: Decision making did
      not follow the sequence of phases assumed by normative models and conveyed in
      current operational guidance but instead was influenced by both reflective and
      reflexive processes. APPLICATION: These results have clear implications for
      understanding operational decision making as it occurs in situ and suggest a need
      for future guidance and training to acknowledge the role of reflexive processes.

PMID- 25875156
TI  - Diversity-Oriented Approaches to Polycyclics and Bioinspired Molecules via the
      Diels-Alder Strategy: Green Chemistry, Synthetic Economy, and Beyond.
AB  - We describe diverse approaches to various dienes and their utilization in the
      Diels-Alder reaction to produce a variety of polycycles. The dienes covered here
      are prepared by simple alkylation reaction or via the Claisen rearrangement or by
      enyne metathesis of alkyne or enyne building blocks. Here, we have also included
      the Diels-Alder chemistry of dendralenes, a higher analog of cross-conjugated
      dienes. The present article is inclusive of o-xylylene derivatives that are
      generated in situ starting with benzosultine or benzosulfone derivatives. The
      Diels-Alder reaction of these dienes with various dienophiles gave diverse
      polycyclic systems and biologically important targets. 

PMID- 25875157
TI  - Colorectal cancer incidence in the Aboriginal population of Ontario, 1998 to
      2009.
AB  - BACKGROUND: Studies suggest that colorectal cancer incidence increased
      disproportionately among the Aboriginal population of Ontario relative to the
      general population. Using an ecological approach, this study examined colorectal
      cancer incidence for the 1998-to-2009 period among Aboriginal people living in
      Ontario. DATA AND METHODS: Based on their postal code when they were diagnosed,
      cases of colorectal cancer identified from the Ontario Cancer Registry were
      assigned to census geographic areas with high (33% or more) or low percentages of
      Aboriginal identity residents, using the Postal Code Conversion File Plus
      (PCCF+). To account for potential misclassification by the PCCF+, Indian reserves
      for which assignment through postal codes is likely to be accurate were
      identified. Age-standardized incidence rates and rate ratios were calculated to
      compare colorectal cancer incidence in high-Aboriginal identity areas or on
      Indian reserves with incidence in low-Aboriginal identity areas. RESULTS:
      Colorectal cancer incidence was significantly higher for residents of high-
      versus low-Aboriginal identity areas in Ontario (rate ratio for men = 1.44, 95%
      CI = 1.26-1.63; rate ratio for women = 1.42, 95% CI = 1.23-1.63), a disparity
      that persisted by age group. When the Aboriginal sample was limited to residents
      of Indian reserves, the difference was statistically significant only for men and
      for people aged 50 to 74. INTERPRETATION: The incidence of colorectal cancer
      differs across areas of Ontario with high and low percentages of Aboriginal
      identity residents.

PMID- 25875158
TI  - Prevalence and correlates of marijuana use in Canada, 2012.
AB  - Based on data from the 2012 Canadian Community Health Survey--Mental Health, past
      year and lifetime marijuana use among the household population aged 15 or older
      in the 10 provinces was examined. In 2012, 42.5% of the population reported
      having ever used marijuana, and 12.2% reported use in the past year. At 33.3%,
      the prevalence of past-year marijuana use was higher among 18- to 24-year-olds
      than among other age groups (20.0% at ages 15 to 17, 15.6% at ages 25 to 44, 6.7%
      at ages 45 to 64, and 0.8% at age 65 or older). Past-year use was higher in
      British Columbia and Nova Scotia and lower in Saskatchewan, compared with the
      rest of Canada. While the overall percentage of people reporting past-year use in
      2012 was unchanged from 2002, the percentage of males who had ever used marijuana
      rose from 47.0% to 49.4%; among females, the prevalence of lifetime use remained
      stable at 36%.

PMID- 25875159
TI  - Dietary carbohydrate and prostate cancer risk: a meta-analysis.
AB  - Carbohydrate intake has been inconsistently associated with risk of prostate
      cancer. We review and quantitatively summarize the evidence from observational
      studies in a meta-analysis. We searched the PubMed database for observational
      studies related to the association of carbohydrate intake and prostate cancer
      risk up to December 25, 2013. Summary relative risks (RRs) were estimated by the
      use of a random effects model. We included 13 case-control studies with 4,367
      cases and 6,205 controls, and 5 cohort studies with 3,679 cases and 74,115
      participants in this meta-analysis. The summary RR of prostate cancer for the
      highest vs. the lowest carbohydrate intake was 1.06 [95% confidence interval
      (CI): 0.93-1.20, I(2) = 46.8%] for all included studies. In the subgroup analyses
      stratified by study design, the summary RRs for the highest vs. the lowest
      carbohydrate intake were 1.04 (95% CI: 0.87-1.23) for case-control studies and
      1.06 (95% CI: 0.88-1.28) for cohort studies. For the 5 studies that reported
      results for advanced prostate cancer, the summary RR was 0.92 (95% CI: 0.71
      1.20). This meta-analysis of observational studies indicates that there is no
      association between carbohydrate intake and prostate cancer risk. Further studies
      are needed to confirm our findings.

PMID- 25875160
TI  - Regret on choice of colorectal cancer screening modality was associated with
      poorer screening compliance: a 4-year prospective cohort study.
AB  - PURPOSE: Very few studies examined the issue of regret on choosing colorectal
      cancer (CRC) screening tests. We evaluated the determinants of regret and tested
      the hypothesis that regret over screening choices was associated with poorer
      screening compliance. METHODS: A bowel cancer screening centre invited all Hong
      Kong citizens aged 50-70 years who were asymptomatic of CRC to participate in
      free-of-charge screening programmes. Upon attendance they attended health
      seminars on CRC and its screening, and were offered an option to choose yearly
      faecal immunochemical test (FIT) for up to four years vs. one direct colonoscopy.
      They were not allowed to switch the screening option after decision. A self
      administered, four-item validated survey was used to assess whether they
      regretted over their choice (> 2 = regretful from a scale of 0 [no regret]-5
      [extreme regret]). A binary logistic regression model evaluated if initial regret
      over their choice was associated with poorer programme compliance. RESULTS: From
      4,341 screening participants who have chosen FIT or colonoscopy, 120 (2.8%)
      regretted over their decision and 1,029 (23.7%) were non-compliant with the
      screening programme. Younger subjects and people who felt pressure when making
      their decision were associated with regret. People who regretted their decision
      were 2.189 (95% C.I. 1.361-3.521, p = 0.001) times more likely to be non
      compliant with the programme. CONCLUSIONS: This study is the first to show that
      regret over the initial CRC screening choice was associated with later non
      compliance. Screening participants who expressed regret over their choice should
      receive additional reminders to improve their programmatic compliance.

PMID- 25875161
TI  - Bioaccumulation and biomagnification of classical flame retardants, related
      halogenated natural compounds and alternative flame retardants in three
      delphinids from Southern European waters.
AB  - Occurrence and behaviour of classical (PBDEs) and alternative (HNs, HBB, PBEB,
      DBDPE and HBCD) flame retardants, together with naturally produced MeO-PBDEs,
      were studied in short-beaked common dolphin (Delphinus delphis), bottlenose
      dolphin (Tursiops truncatus) and long-finned pilot whale (Globicephala melas) in
      two sampling locations from Southern European waters. PBDEs, Dec 602, Dec 603,
      DP, alpha-HBCD and two MeO-PBDEs were detected in all three species. ?PBDEs were
      between 17 and 2680 ng/g lw; ?HNs were between 1.1 and 59 ng/g lw; alpha-HBCD
      levels ranged between 3.2 and 641 ng/g lw; ?MeO-PBDEs were between 34 and 1966
      ng/g lw. Bottlenose dolphins were the most contaminated species and some
      individuals could present health risk for endocrine disruption since levels found
      were above the reported threshold (1500 ng/g lw). Stable isotope analysis was
      used to evaluate the biomagnification capacity of these compounds. PBDEs, MeO
      PBDEs and Dec 602 showed a significant positive correlation with trophic
      position.

PMID- 25875162
TI  - Ambient air pollution, temperature and out-of-hospital coronary deaths in
      Shanghai, China.
AB  - Few studies have evaluated the effects of ambient air pollution and temperature
      in triggering out-of-hospital coronary deaths (OHCDs) in China. We evaluated the
      associations of air pollution and temperature with daily OHCDs in Shanghai, China
      from 2006 to 2011. We applied an over-dispersed generalized additive model and a
      distributed lag nonlinear model to analyze the effects of air pollution and
      temperature, respectively. A 10 MUg/m(3) increase in the present-day PM10, PM2.5,
      SO2, NO2 and CO were associated with increases in OHCD mortality of 0.49%, 0.68%,
      0.88%, 1.60% and 0.08%, respectively. A 1  degrees C decrease below the minimum
      mortality temperature corresponded to a 3.81% increase in OHCD mortality on lags
      days 0-21, and a 1  degrees C increase above minimum-mortality temperature
      corresponded to a 4.61% increase over lag days 0-3. No effects were found for in
      hospital coronary deaths. This analysis suggests that air pollution, low
      temperature and high temperature may increase the risk of OHCDs.

PMID- 25875163
TI  - Heteroaggregation, transformation and fate of CeO2 nanoparticles in wastewater
      treatment.
AB  - Wastewater Treatment Plants (WWTPs) are a key pathway by which nanoparticles
      (NPs) enter the environment following release from NP-enabled products. This work
      considers the fate and exposure of CeO2 NPs in WWTPs in a two-step process of
      heteroaggregation with bacteria followed by the subsequent reduction of Ce(IV) to
      Ce(III). Measurements of NP association with solids in sludge were combined with
      experimental estimates of reduction rate constants for CeO2 NPs in Monte Carlo
      simulations to predict the concentrations and speciation of Ce in WWTP effluents
      and biosolids. Experiments indicated preferential accumulation of CeO2 NPs in
      biosolids where reductive transformation would occur. Surface functionalization
      was observed to impact both the distribution coefficient and the rates of
      transformation. The relative affinity of CeO2 NPs for bacterial suspensions in
      sludge appears to explain differences in the observed rates of Ce reduction for
      the two types of CeO2 NPs studied.

PMID- 25875164
TI  - Catalytic analysis of APOBEC3G involving real-time NMR spectroscopy reveals
      nucleic acid determinants for deamination.
AB  - APOBEC3G (A3G) is a single-stranded DNA-specific cytidine deaminase that
      preferentially converts cytidine to uridine at the third position of triplet
      cytosine (CCC) hotspots. A3G restricts the infectivity of viruses, such as HIV-1,
      by targeting CCC hotspots scattered through minus DNA strands, reverse
      transcribed from genomic RNA. Previously, we developed a real-time NMR method and
      elucidated the origin of the 3'->5' polarity of deamination of DNA by the C
      terminal domain of A3G (CD2), which is a phenomenon by which a hotspot located
      closer to the 5'-end is deaminated more effectively than one less close to the 5'
      end, through quantitative analysis involving nonspecific binding to and sliding
      along DNA. In the present study we applied the real-time NMR method to analyze
      the catalytic activity of CD2 toward DNA oligonucleotides containing a nucleotide
      analog at a single or multiple positions. Analyses revealed the importance of the
      sugar and base moieties throughout the consecutive 5 nucleotides, the CCC hotspot
      being positioned at the center. It was also shown that the sugar or base moieties
      of the nucleotides outside this 5 nucleotide recognition sequence are also
      relevant as to CD2's activity. Analyses involving DNA oligonucleotides having two
      CCC hotspots linked by a long sequence of either deoxyribonucleotides,
      ribonucleotides or abasic deoxyribonucleotides suggested that the phosphate
      backbone is required for CD2 to slide along the DNA strand and to exert the 3'
      >5' polarity. Examination of the effects of different salt concentrations on the
      3'->5' polarity indicated that the higher the salt concentration, the less
      prominent the 3'->5' polarity. This is most likely the result of alleviation of
      sliding due to a decrease in the affinity of CD2 with the phosphate backbone at
      high salt concentrations. We also investigated the reactivity of substrates
      containing 5-methylcytidine (5mC) or 5-hydroxymethylcytidine, and found that A3G
      exhibited low activity toward 5mC. 

PMID- 25875165
TI  - Longitudinal associations between physical and cognitive performance among
      community-dwelling older adults.
AB  - To assess the directionality of the association between physical and cognitive
      decline in later life, we compared patterns of decline in performance across
      groups defined by baseline presence of cognitive and/or physical impairment [none
      (n = 217); physical only (n = 169); cognitive only (n = 158), or both (n = 220)]
      in a large sample of participants in a cognitive aging study at the Knight
      Alzheimer's Disease Research Center at Washington University in St. Louis who
      were followed for up to 8 years (3,079 observations). Rates of decline reached
      20% for physical performance and varied across cognitive tests (global, memory,
      speed, executive function, and visuospatial skills). We found that physical
      decline was better predicted by baseline cognitive impairment (slope = -1.22,
      p<0.001), with baseline physical impairment not contributing to further decline
      in physical performance (slope = -0.25, p = 0.294). In turn, baseline physical
      impairment was only marginally associated with rate of cognitive decline across
      various cognitive domains. The cognitive-functional association is likely to
      operate in the direction of cognitive impairment to physical decline although
      physical impairment may also play a role in cognitive decline/dementia.
      Interventions to prevent further functional decline and development of disability
      and complete dependence may benefit if targeted to individuals with cognitive
      impairment who are at increased risk. 

PMID- 25875166
TI  - Effects of moderate amounts of barley in late pregnancy on growth, glucose
      metabolism and osteoarticular status of pre-weaning horses.
AB  - In stud management, broodmares are commonly fed concentrates in late pregnancy.
      This practice, however, was shown to correlate with an increased incidence of
      osteochondrosis in foals, which may be related to insulin sensitivity. We
      hypothesized that supplementation of the mare with barley in the last trimester
      of pregnancy alters the pre-weaning foal growth, glucose metabolism and
      osteoarticular status. Here, pregnant multiparous saddlebred mares were fed
      forage only (group F, n=13) or both forage and cracked barley (group B, n=12)
      from the 7th month of pregnancy until term, as calculated to cover nutritional
      needs of broodmares. Diets were given in two daily meals. All mares and foals
      returned to pasture after parturition. Post-natal growth, glucose metabolism and
      osteoarticular status were investigated in pre-weaning foals. B mares maintained
      an optimal body condition score (>3.5), whereas that of F mares decreased and
      remained low (<2.5) up to 3 months of lactation, with a significantly lower
      bodyweight (-7%) than B mares throughout the last 2 months of pregnancy. B mares
      had increased plasma glucose and insulin after the first meal and after the
      second meal to a lesser extent, which was not observed in F mares. B mares also
      had increased insulin secretion during an intravenous glucose tolerance test
      (IVGTT). Plasma NEFA and leptin were only temporarily affected by diet in mares
      during pregnancy or in early lactation. Neonatal B foals had increased serum
      osteocalcin and slightly increased glucose increments and clearance after glucose
      injection, but these effects had vanished at weaning. Body measurements, plasma
      IGF-1, T4, T3, NEFA and leptin concentrations, insulin secretion during IVGTT, as
      well as glucose metabolism rate during euglycemic hyperinsulinemic clamps after
      weaning, did not differ between groups. Radiographic examination of joints
      indicated increased osteochondrosis relative risk in B foals, but this was not
      significant. These data demonstrate that B or F maternal nutrition has very few
      effects on foal growth, endocrinology and glucose homeostasis until weaning, but
      may induce cartilage lesions. 

PMID- 25875168
TI  - Correction: involvement of TNF-alpha converting enzyme in the development of
      psoriasis-like lesions in a mouse model.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0112408.]. 

PMID- 25875167
TI  - Prevalence of human papillomavirus genotypes among African women with normal
      cervical cytology and neoplasia: a systematic review and meta-analysis.
AB  - BACKGROUND: Several meta-analyses confirmed the five most prevalent human
      papillomavirus (HPV) strains in women with and without cervical neoplastic
      diseases are HPV16, 18, 31, 52, and 58. HPV16/18 are the predominant oncogenic
      genotypes, causing approximately 70% of global cervical cancer cases. The vast
      majority of the women studied in previous analyses were from Europe, North
      America, Asia, and most recently Latin America and the Caribbean. Despite the
      high burden of cervical cancer morbidity and mortality in Africa, a robust meta
      analysis of HPV genotype prevalence and distribution in African women is lacking.
      METHODS AND FINDINGS: We systematically searched 14 major databases from
      inception to August 2013 without language restriction, following the Meta
      Analysis of Observational Studies in Epidemiology and the Preferred Reporting
      Items for Systematic Reviews and Meta-Analyses guidelines. Seventy-one studies
      from 23 African countries were identified after screening 1162 citations and data
      abstracted and study quality appraised from 195 articles. HPV type-specific
      prevalence and distribution was estimated from 17,273 cases of women with normal
      cervical cytology; 1019 women with atypical squamous cells of undetermined
      significance (ASCUS); 1444 women with low-grade squamous intraepithelial lesion
      (LSIL); 1571 women with high-grade squamous intraepithelial lesion (HSIL); and
      4,067 cases of invasive cervical carcinoma (ICC). Overall prevalence of HPV16/18
      were 4.4% and 2.8% of women with normal cytology, 12.0% and 4.4% with ASCUS,
      14.5% and 10.0% with LSIL, 31.2% and 13.9% with HSIL, and 49.7% and 18.0% with
      ICC, respectively. Study limitations include the lack of adequate data from
      Middle and Northern African regions, and variations in the HPV type-specific
      sensitivity of different genotyping protocols. CONCLUSIONS: To our knowledge,
      this study is the most comprehensive assessment of the overall prevalence and
      distribution of HPV genotypes in African women with and without different
      cervical neoplasias. We have established that HPV16/18 account for 67.7% of ICC
      cases among African women. Based on our findings, we highly recommend the
      administration of existing prophylactic vaccines to younger women not infected
      with HPV16/18 and an increase in HPV screening efforts for high-risk genotypes to
      prevent cervical cancer. REVIEW REGISTRATION: International Prospective Register
      of Systematic Reviews CRD42013006558.

PMID- 25875169
TI  - Visualizing the indefinable: three-dimensional complexity of 'infectious
      diseases'.
AB  - BACKGROUND: The words 'infection' and 'inflammation' lack specific definitions.
      Here, such words are not defined. Instead, the ability to visualize host
      microbial interactions was explored. METHODS: Leukocyte differential counts and
      four bacterial species (Staphylococcus aureus, Streptococcus dysgalactiae,
      Staphylococcus chromogenes, and Escherichia coli) were determined or isolated in
      a cross-sectional and randomized study conducted with 611 bovine milk samples.
      Two paradigms were evaluated: (i) the classic one, which measures non-structured
      (count or percent) data; and (ii) a method that, using complex data structures,
      detects and differentiates three-dimensional (3D) interactions among lymphocytes
      (L), macrophages (M), and neutrophils (N). RESULTS: Classic analyses failed to
      differentiate bacterial-positive (B+) from -negative (B-) observations: B- and B+
      data overlapped, even when statistical significance was achieved. In contrast,
      the alternative approach showed distinct patterns, such as perpendicular data
      inflections, which discriminated microbial-negative/mononuclear cell
      predominating (MCP) from microbial-positive/phagocyte-predominating (PP) subsets.
      Two PP subcategories were distinguished, as well as PP/culture-negative (false
      negative) and MCP/culture-positive (false-positive) observations. In 3D space,
      MCP and PP subsets were perpendicular to one another, displaying >= 91%
      specificity or sensitivity. Findings supported five inferences: (i) disease is
      not always ruled out by negative bacterial tests; (ii) low total cell counts can
      coexist with high phagocyte percents; (iii) neither positive bacterial isolation
      nor high cell counts always coincide with PP profiles; (iv) statistical
      significance is not synonymous with discrimination; and (v) hidden relationships
      cannot be detected when simple (non-structured) data formats are used and
      statistical analyses are performed before data subsets are identified, but can be
      uncovered when complexity is investigated. CONCLUSIONS: Pattern recognition-based
      assessments can detect host-microbial interactions usually unobserved. Such
      cutoff-free, confidence interval-free, gold standard-free approaches provide
      interpretable information on complex entities, such as 'infection' and
      'inflammation', even without definitions. To investigate disease dynamics,
      combinations of observational and experimental longitudinal studies, on human and
      non-human infections, are recommended.

PMID- 25875170
TI  - Association between the European GWAS-identified susceptibility locus at
      chromosome 4p16 and the risk of atrial septal defect: a case-control study in
      Southwest China and a meta-analysis.
AB  - Atrial septal defect (ASD) is the third most frequent type of congenital heart
      anomaly, featuring shunting of blood between the two atria. Gene-environment
      interaction remains to be an acknowledged cause for ASD occurrence. A recent
      European genome-wide association study (GWAS) of congenital heart disease (CHD)
      identified 3 susceptibility SNPs at chromosome 4p16 associated with ASD:
      rs870142, rs16835979 and rs6824295. A Chinese-GWAS of CHD conducted in the
      corresponding period did not reveal the 3 susceptibility SNPs, but reported 2
      different risk SNPs: rs2474937 and rs1531070. Therefore, we aimed to investigate
      the associations between the 3 European GWAS-identified susceptibility SNPs and
      ASD risk in the Han population in southwest China. Additionally, to increase the
      robustness of our current analysis, we conducted a meta-analysis combining
      published studies and our current case-control study. We performed association,
      linkage disequilibrium, and haplotype analysis among the 3 SNPs in 190 ASD cases
      and 225 age-, sex-, and ethnicity-matched healthy controls. Genotype and allele
      frequencies among the 3 SNPs showed statistically significant differences between
      the cases and controls. Our study found that individuals carrying the allele T of
      rs870142, the allele A of rs16835979, and the allele T of rs6824295 had a
      respective 50.1% (odds ratio (OR) = 1.501, 95% confidence interval (CI) = 1.122
      2.009, PFDR-BH = 0.018), 48.5% (OR = 1.485, 95%CI = 1.109-1.987, PFDR-BH =
      0.012), and 38.6% (OR = 1.386, 95%CI = 1.042-1.844, PFDR-BH = 0.025) increased
      risk to develop ASD than wild-type allele carriers in our study cohort. In the
      haplotype analysis, we identified a disease-risk haplotype (TAT) (OR = 1.540,
      95%CI = 1.030-2.380, PFDR-BH = 0.016). Our meta-analysis also showed that the
      investigated SNP was associated with ASD risk (combined OR (95%CI) = 1.35 (1.24
      1.46), P < 0.00001). Our study provides compelling evidence to motivate better
      understanding of the etiology of ASD. 

PMID- 25875171
TI  - SERPINB11 frameshift variant associated with novel hoof specific phenotype in
      Connemara ponies.
AB  - Horses belong to the order Perissodactyla and bear the majority of their weight
      on their third toe; therefore, tremendous force is applied to each hoof. An
      inherited disease characterized by a phenotype restricted to the dorsal hoof wall
      was identified in the Connemara pony. Hoof wall separation disease (HWSD)
      manifests clinically as separation of the dorsal hoof wall along the weight
      bearing surface of the hoof during the first year of life. Parents of affected
      ponies appeared clinically normal, suggesting an autosomal recessive mode of
      inheritance. A case-control allelic genome wide association analysis was
      performed (ncases = 15, ncontrols = 24). Population stratification (lambda =
      1.48) was successfully improved by removing outliers (ncontrols = 7) identified
      on a multidimensional scaling plot. A genome-wide significant association was
      detected on chromosome 8 (praw = 1.37x10-10, pgenome = 1.92x10-5). A homozygous
      region identified in affected ponies spanned from 79,936,024-81,676,900 bp and
      contained a family of 13 annotated SERPINB genes. Whole genome next-generation
      sequencing at 6x coverage of two cases and two controls revealed 9,758 SNVs and
      1,230 indels within the ~1.7-Mb haplotype, of which 17 and 5, respectively,
      segregated with the disease and were located within or adjacent to genes.
      Additional genotyping of these 22 putative functional variants in 369 Connemara
      ponies (ncases = 23, ncontrols = 346) and 169 horses of other breeds revealed
      segregation of three putative variants adjacent or within four SERPIN genes. Two
      of the variants were non-coding and one was an insertion within SERPINB11 that
      introduced a frameshift resulting in a premature stop codon. Evaluation of mRNA
      levels at the proximal hoof capsule (ncases = 4, ncontrols = 4) revealed that
      SERPINB11 expression was significantly reduced in affected ponies (p<0.001).
      Carrier frequency was estimated at 14.8%. This study describes the first genetic
      variant associated with a hoof wall specific phenotype and suggests a role of
      SERPINB11 in maintaining hoof wall structure. 

PMID- 25875172
TI  - MiR-375 promotes redifferentiation of adult human beta cells expanded in vitro.
AB  - In-vitro expansion of beta cells from adult human pancreatic islets could provide
      abundant cells for cell replacement therapy of diabetes. However, proliferation
      of beta-cell-derived (BCD) cells is associated with dedifferentiation. Here we
      analyzed changes in microRNAs (miRNAs) during BCD cell dedifferentiation and
      identified miR-375 as one of the miRNAs greatly downregulated. We hypothesized
      that restoration of miR-375 expression in expanded BCD cells may contribute to
      their redifferentiation. Our findings demonstrate that overexpression of miR-375
      alone leads to activation of beta-cell gene expression, reduced cell
      proliferation, and a switch from N-cadherin to E-cadherin expression, which
      characterizes mesenchymal-epithelial transition. These effects, which are
      reproducible in cells derived from multiple human donors, are likely mediated by
      repression of PDPK1 transcripts and indirect downregulation of GSK3 activity.
      These findings support an important role of miR-375 in regulation of human beta
      cell phenotype, and suggest that miR-375 upregulation may facilitate the
      generation of functional insulin-producing cells following ex-vivo expansion of
      human islet cells. 

PMID- 25875173
TI  - YKL-40/c-Met expression in rectal cancer biopsies predicts tumor regression
      following neoadjuvant chemoradiotherapy: a multi-institutional study.
AB  - BACKGROUND: Neoadjuvant chemo-radiotherapy (CRT) followed by surgical resection
      is the standard treatment for locally advanced rectal cancer, although complete
      tumor pathological regression is achieved in only up to 30% of cases. A
      clinicopathological and molecular predictive stratification of patients with
      advanced rectal cancer is still lacking. Here, c-Met and YKL-40 have been studied
      as putative predictors of CRT response in rectal cancer, due to their reported
      involvement in chemoradioresistance in various solid tumors. MATERIAL AND
      METHODS: A multicentric study was designed to assess the role of c-Met and YKL-40
      expression in predicting chemoradioresistance and to correlate clinical and
      pathological features with CRT response. Immunohistochemistry and fluorescent in
      situ hybridization for c-Met were performed on 81 rectal cancer biopsies from
      patients with locally advanced rectal adenocarcinoma. All patients underwent
      standard (50.4 gy in 28 fractions + concurrent capecitabine 825 mg/m2)
      neoadjuvant CRT or the XELOXART protocol. CRT response was documented on surgical
      resection specimens and recorded as tumor regression grade (TRG) according to the
      Mandard criteria. RESULTS: A significant correlation between c-Met and YKL-40
      expression was observed (R = 0.43). The expressions of c-Met and YKL-40 were both
      significantly associated with a lack of complete response (86% and 87% of c-Met
      and YKL-40 positive cases, p< 0.01 and p = 0.006, respectively). Thirty of the 32
      biopsies co-expressing both markers had partial or absent tumor response (TRG 2
      5), strengthening their positive predictive value (94%). The exclusive predictive
      role of YKL-40 and c-Met was confirmed using a multivariate analysis (p = 0.004
      and p = 0.007 for YKL-40 and c-Met, respectively). TRG was the sole morphological
      parameter associated with poor outcome. CONCLUSION: c-Met and YKL-40 expression
      is a reliable predictor of partial/absent response to neoadjuvant CRT in rectal
      cancer. Targeted therapy protocols could take advantage of prior evaluations of c
      MET and YKL-40 expression levels to increase therapeutic efficacy.

PMID- 25875174
TI  - Treatment of Bone Loss With the Induced Membrane Technique: Techniques and
      Outcomes.
AB  - OBJECTIVES: To critically review the outcomes and issues associated with the
      induced membrane technique in a trauma population. DESIGN: Retrospective case
      series, Level IV therapeutic study. SETTING: Urban Level I trauma center.
      PATIENTS: Sixty-nine patients aged 18 years or older who underwent treatment of
      bone loss with the induced membrane technique. INTERVENTION: All patients
      underwent open treatment of their traumatic bone loss with a 2-stage induced
      membrane technique. MAIN OUTCOME MEASUREMENT: Bony union rate, as evaluated with
      radiographic and clinical signs of healing. RESULTS: Patients in this series
      averaged 4.4 surgeries, which included initial debridement to definitive
      fixation. The tibia was the most common site of bone loss, encompassing 50.7% of
      the series, whereas femoral bone loss was next at 24.6%. Polymethylmethacrylate
      spacers were in place for a mean of 11.2 weeks (mode of 8 weeks) before bone
      grafting for an average bony defect volume of 76.6 cm. Union was obtained in
      82.6% of patients at a mean of 26.6 weeks after grafting. Mean follow-up for
      these patients was 23.8 months. CONCLUSIONS: The induced membrane technique is an
      effective method to obtain bony union when used in the trauma population.
      However, it is not foolproof, and attention must be paid to the critical
      subtleties of the procedure. Further investigation is needed to help determine
      the optimal spacer composition and other technical aspects of the procedure such
      as timing of the exchange. LEVEL OF EVIDENCE: Therapeutic Level IV. See
      Instructions for Authors for a complete description of levels of evidence.

PMID- 25875175
TI  - Traction Neurectomy for Treatment of Painful Residual Limb Neuroma in Lower
      Extremity Amputees.
AB  - OBJECTIVES: To describe the outcomes of traction neurectomy as a surgical
      treatment for symptomatic neuroma of the residual lower extremity and to identify
      clinical and/or demographic factors associated with an increased likelihood of
      persistent or recurrent pain after surgery. DESIGN: Retrospective Cohort Study.
      SETTING: Amputee clinic at a Level I Trauma Center. PATIENTS: Inclusion required
      a history of transfemoral or transtibial amputation and a history of symptomatic
      neuroma(s) at the residual limb treated with traction neurectomy. Twelve months
      of clinical follow-up or the recurrence of neuroma-type pains was required for
      inclusion. Thirty-eight patients (63 nerves) comprised the study group.
      INTERVENTION: Traction neurectomy for treatment of symptomatic neuroma. MAIN
      OUTCOME MEASURES: The primary outcome was the presence or absence of persistent
      or recurrent neuroma-type pain at last follow-up. The secondary outcome was
      reoperation for persistent or recurrent symptomatic neuroma. RESULTS: Sixteen of
      38 patients (42%) had recurrent or persistent neuroma-type pain at a mean follow
      up of 37 months (range, 11-91 months), and 8/38 (21%) have undergone subsequent
      surgical treatment. Among the demographic and clinical features examined, only
      male gender was found to be a statistically significant predictor of persistent
      or recurrent neuroma-type pain. CONCLUSIONS: Traction neurectomy results in a
      high rate of persistent or recurrent neuroma-type and that surgeons should be
      cautious when considering it for the treatment of symptomatic neuroma of the
      residual lower extremity. Furthermore, efforts to identify better surgical and
      nonsurgical treatments for this problem are justified. LEVEL OF EVIDENCE:
      Therapeutic Level IV. See Instructions for Authors for a complete description of
      levels of evidence.

PMID- 25875177
TI  - Objective assessment and design improvement of a staring, sparse transducer array
      by the spatial crosstalk matrix for 3D photoacoustic tomography.
AB  - Accurate reconstruction of 3D photoacoustic (PA) images requires detection of
      photoacoustic signals from many angles. Several groups have adopted staring
      ultrasound arrays, but assessment of array performance has been limited. We
      previously reported on a method to calibrate a 3D PA tomography (PAT) staring
      array system and analyze system performance using singular value decomposition
      (SVD). The developed SVD metric, however, was impractical for large system
      matrices, which are typical of 3D PAT problems. The present study consisted of
      two main objectives. The first objective aimed to introduce the crosstalk matrix
      concept to the field of PAT for system design. Figures-of-merit utilized in this
      study were root mean square error, peak signal-to-noise ratio, mean absolute
      error, and a three dimensional structural similarity index, which were derived
      between the normalized spatial crosstalk matrix and the identity matrix. The
      applicability of this approach for 3D PAT was validated by observing the response
      of the figures-of-merit in relation to well-understood PAT sampling
      characteristics (i.e. spatial and temporal sampling rate). The second objective
      aimed to utilize the figures-of-merit to characterize and improve the performance
      of a near-spherical staring array design. Transducer arrangement, array radius,
      and array angular coverage were the design parameters examined. We observed that
      the performance of a 129-element staring transducer array for 3D PAT could be
      improved by selection of optimal values of the design parameters. The results
      suggested that this formulation could be used to objectively characterize 3D PAT
      system performance and would enable the development of efficient strategies for
      system design optimization. 

PMID- 25875178
TI  - Cajal body proteins differentially affect the processing of box C/D scaRNPs.
AB  - Small nuclear ribonucleoproteins (snRNPs), which are required for pre-mRNA
      splicing, contain extensively modified snRNA. Small Cajal body-specific
      ribonucleoproteins (scaRNPs) mediate these modifications. It is unknown how the
      box C/D class of scaRNPs localizes to Cajal Bodies (CBs). The processing of box
      C/D scaRNA is also unclear. Here, we explore the processing of box C/D scaRNA 2
      and 9 by coilin. We also broaden our investigation to include WRAP53 and SMN,
      which accumulate in CBs, play a role in RNP biogenesis and associate with coilin.
      These studies demonstrate that the processing of an ectopically expressed scaRNA2
      is altered upon the reduction of coilin, WRAP53 or SMN, but the extent and
      direction of this change varies depending on the protein reduced. We also show
      that box C/D scaRNP activity is reduced in a cell line derived from coilin
      knockout mice. Collectively, the findings presented here further implicate coilin
      as being a direct participant in the formation of box C/D scaRNPs, and
      demonstrate that WRAP53 and SMN may also play a role, but the activity of these
      proteins is divergent to coilin. 

PMID- 25875176
TI  - Functional synergy between cholecystokinin receptors CCKAR and CCKBR in mammalian
      brain development.
AB  - Cholecystokinin (CCK), a peptide hormone and one of the most abundant
      neuropeptides in vertebrate brain, mediates its actions via two G-protein coupled
      receptors, CCKAR and CCKBR, respectively active in peripheral organs and the
      central nervous system. Here, we demonstrate that the CCK receptors have a
      dynamic and largely reciprocal expression in embryonic and postnatal brain. Using
      compound homozygous mutant mice lacking the activity of both CCK receptors, we
      uncover their additive, functionally synergistic effects in brain development and
      demonstrate that CCK receptor loss leads to abnormalities of cortical
      development, including defects in the formation of the midline and corpus
      callosum, and cortical interneuron migration. Using comparative transcriptome
      analysis of embryonic neocortex, we define the molecular mechanisms underlying
      these defects. Thus we demonstrate a developmental, hitherto unappreciated, role
      of the two CCK receptors in mammalian neocortical development. 

PMID- 25875179
TI  - Light-sensitive vertical migration of the Japanese eel Anguilla japonica revealed
      by real-time tracking and its utilization for geolocation.
AB  - Short-time tracking (one to eight days) of the Japanese eel (Anguilla japonica)
      using ultrasonic transmitter was performed in the tropical-subtropical area
      adjacent to the spawning area and temperate area off the Japanese Archipelago. Of
      16 eels (11 wild and five farmed) used, 10 wild eels displayed clear diel
      vertical migration (DVM) from the beginning, while the other five farmed eels
      tracked for 19 to 66 hours did not. During daytime, a significantly positive
      correlation between migration depth and light intensity recorded on the vessel
      was observed in the 10 wild eels, indicating that the eels were sensitive to
      sunlight even at the middle to lower mesopelagic zone (500 to 800 m). During
      nighttime, the eel migration depth was observed to be associated with the phase,
      rising and setting of the moon, indicating that the eels were sensitive to
      moonlight at the upper mesopelagic zone (<300 m). Two of 10 wild eels were in the
      yellow stage but shared similar DVM with the silver stage eels. Swimbladders of
      three silver stage eels were punctured before releasing, but very little effect
      on DVM was observed. The eels very punctually initiated descent upon nautical
      dawn and ascent upon sunset, enabling us to determine local times for sunrise and
      sunset, and hence this behavior may be used for geolocating eels. In fact,
      estimated positions of eels based on the depth trajectory data were comparable or
      even better than those obtained by light-based archival tag in other fish
      species. 

PMID- 25875180
TI  - Sphingobium fuliginis HC3: a novel and robust isolated biphenyl- and
      polychlorinated biphenyls-degrading bacterium without dead-end intermediates
      accumulation.
AB  - Biphenyl and polychlorinated biphenyls (PCBs) are typical environmental
      pollutants. However, these pollutants are hard to be totally mineralized by
      environmental microorganisms. One reason for this is the accumulation of dead-end
      intermediates during biphenyl and PCBs biodegradation, especially benzoate and
      chlorobenzoates (CBAs). Until now, only a few microorganisms have been reported
      to have the ability to completely mineralize biphenyl and PCBs. In this research,
      a novel bacterium HC3, which could degrade biphenyl and PCBs without dead-end
      intermediates accumulation, was isolated from PCBs-contaminated soil and
      identified as Sphingobium fuliginis. Benzoate and 3-chlorobenzoate (3-CBA)
      transformed from biphenyl and 3-chlorobiphenyl (3-CB) could be rapidly degraded
      by HC3. This strain has strong degradation ability of biphenyl, lower chlorinated
      (mono-, di- and tri-) PCBs as well as mono-CBAs, and the biphenyl/PCBs catabolic
      genes of HC3 are cloned on its plasmid. It could degrade 80.7% of 100 mg L -1
      biphenyl within 24 h and its biphenyl degradation ability could be enhanced by
      adding readily available carbon sources such as tryptone and yeast extract. As
      far as we know, HC3 is the first reported that can degrade biphenyl and 3-CB
      without accumulation of benzoate and 3-CBA in the genus Sphingobium, which
      indicates the bacterium has the potential to totally mineralize biphenyl/PCBs and
      might be a good candidate for restoring biphenyl/PCBs-polluted environments. 

PMID- 25875181
TI  - Health risks and changes in self-efficacy following community health screening of
      adults with serious mental illnesses.
AB  - Physical health screenings were conducted by researchers and peer wellness
      specialists for adults attending publicly-funded community mental health
      programs. A total of 457 adults with serious mental illnesses attended health
      fairs in 4 U.S. states and were screened for 8 common medical co-morbidities and
      health risk factors. Also assessed were self-reported health competencies,
      medical conditions, and health service utilization. Compared to non
      institutionalized U.S. adults, markedly higher proportions screened positive for
      obesity (60%), hypertension (32%), diabetes (14%), smoking (44%), nicotine
      dependence (62%), alcohol abuse (17%), drug abuse (11%), and coronary heart
      disease (10%). A lower proportion screened positive for hyperlipidemia (7%).
      Multivariable random regression analysis found significant pre- to post-screening
      increases in participants' self-rated abilities for health practices, competence
      for health maintenance, and health locus of control. Screening identified 82
      instances of undiagnosed diabetes, hypertension or hyperlipidemia, and 76
      instances where these disorders were treated but uncontrolled. These results are
      discussed in the context of how this global public health approach holds promise
      for furthering the goal of integrating health and mental health care. 

PMID- 25875182
TI  - Perfusion MRI derived indices of microvascular shunting and flow control
      correlate with tumor grade and outcome in patients with cerebral glioma.
AB  - OBJECTIVES: Deficient microvascular blood flow control is thought to cause tumor
      hypoxia and increase resistance to therapy. In glioma patients, we tested whether
      perfusion-weighted MRI (PWI) based indices of microvascular flow control provide
      more information on tumor grade and patient outcome than does the established PWI
      angiogenesis marker, cerebral blood volume (CBV). MATERIAL AND METHODS: Seventy
      two glioma patients (sixty high-grade, twelve low-grade gliomas) were included.
      Capillary transit time heterogeneity (CTH) and the coefficient of variation
      (COV), its ratio to blood mean transit time, provide indices of microvascular
      flow control and the extent to which oxygen can be extracted by tumor tissue. The
      ability of these parameters and CBV to differentiate tumor grade were assessed by
      receiver operating characteristic curves and logistic regression. Their ability
      to predict time to progression and overall survival was examined by the Cox
      proportional-hazards regression model, and by survival curves using log-rank
      tests. RESULTS: The best prediction of grade (AUC = 0.876; p < 0.05) was achieved
      by combining knowledge of CBV and CTH in the enhancing tumor and peri-focal
      edema, and patients with glioblastoma multiforme were identified best by CTH (AUC
      = 0.763; p<0.001). CTH outperformed CBV and COV in predicting time to progression
      and survival in all gliomas and in a subgroup consisting of only high-grade
      gliomas. CONCLUSION: Our study confirms the importance of microvascular flow
      control in tumor growth by demonstrating that determining CTH improves tumor
      grading and outcome prediction in glioma patients compared to CBV alone.

PMID- 25875184
TI  - Core chemistry and skeletal rearrangements of porphyrinoids and
      metalloporphyrinoids.
AB  - Core alteration, affording heteroporphyrinoids and carbaporphyrinoids, allows for
      the exploration of porphyrin-like or porphyrin-unlike coordination chemistry.
      Such a strategy has provided a fundamental change in the approach to macrocyclic
      organometallic chemistry. The specific reactivity of porphyrinoids has offered an
      insight into reactions inside particularly shaped macrocyclic architecture,
      including metal-mediated organic transformations. This review focuses on
      alterations of macrocycles, made of four carbocyclic/heterocyclic subunits, which
      resemble the structure of porphyrin or porphyrin isomers, providing, however,
      remarkable porphyrin-like (XNNN), (CNNN), (CNCN) or (C2NNN) surroundings. To
      facilitate the understanding of the discussed subject matter, all addressed
      reactions reflecting core reactivity have been formally grouped into nine
      categories distinguished by the principal type of transformation addressed: (1)
      alkylation or arylation, (2) core heteroatom replacement, (3) oxidation and
      oxygenation, (4) substitution, (5) macrocyclic fusion, (6) core bridging, (7)
      ring contraction, (8) ring expansion, and (9) C-H and C-C bond activation. The
      distinctive macrocyclic environment creates a long-sought opportunity to trap
      unique organometallic transformations which include instances of benzene ring
      contraction to cyclopentadiene or the formation of an unprecedented
      metalloporphyrinoid: 21-pallada-23-telluraporphyrin. This review offers certain
      challenging perspectives which target the goals of organometallic bond
      activation. 

PMID- 25875183
TI  - Murine CMV-induced hearing loss is associated with inner ear inflammation and
      loss of spiral ganglia neurons.
AB  - Congenital human cytomegalovirus (HCMV) occurs in 0.5-1% of live births and
      approximately 10% of infected infants develop hearing loss. The mechanism(s) of
      hearing loss remain unknown. We developed a murine model of CMV induced hearing
      loss in which murine cytomegalovirus (MCMV) infection of newborn mice leads to
      hematogenous spread of virus to the inner ear, induction of inflammatory
      responses, and hearing loss. Characteristics of the hearing loss described in
      infants with congenital HCMV infection were observed including, delayed onset,
      progressive hearing loss, and unilateral hearing loss in this model and, these
      characteristics were viral inoculum dependent. Viral antigens were present in the
      inner ear as were CD(3+) mononuclear cells in the spiral ganglion and stria
      vascularis. Spiral ganglion neuron density was decreased after infection, thus
      providing a mechanism for hearing loss. The lack of significant inner ear
      histopathology and persistence of inflammation in cochlea of mice with hearing
      loss raised the possibility that inflammation was a major component of the
      mechanism(s) of hearing loss in MCMV infected mice.

PMID- 25875185
TI  - Should the "Back to Sleep" campaign be advocated for SUDEP prevention?

PMID- 25875187
TI  - The development of love wave-based humidity sensors incorporating multiple
      layers.
AB  - A Love wave humidity sensor is developed by using a multilayer structure
      consisting of PVA/SiO2 layers on an ST-90 degrees X quartz substrate. The
      theoretical result shows that the sensor with such a two-layer structure can
      achieve a higher sensitivity and a smaller loss than the structures with a single
      polymer layer. Comparative experiments are performed for the sensor incorporating
      PVA/SiO2 layers and the sensor incorporating a PVA layer. The experimental
      results agree well with the theoretical predication. 

PMID- 25875186
TI  - Rapid detection of Ebola virus with a reagent-free, point-of-care biosensor.
AB  - Surface acoustic wave (SAW) sensors can rapidly detect Ebola antigens at the
      point-of-care without the need for added reagents, sample processing, or
      specialized personnel. This preliminary study demonstrates SAW biosensor
      detection of the Ebola virus in a concentration-dependent manner. The detection
      limit with this methodology is below the average level of viremia detected on the
      first day of symptoms by PCR. We observe a log-linear sensor response for highly
      fragmented Ebola viral particles, with a detection limit corresponding to 1.9 *
      104 PFU/mL prior to virus inactivation. We predict greatly improved sensitivity
      for intact, infectious Ebola virus. This point-of-care methodology has the
      potential to detect Ebola viremia prior to symptom onset, greatly enabling
      infection control and rapid treatment. This biosensor platform is powered by
      disposable AA batteries and can be rapidly adapted to detect other emerging
      diseases in austere conditions. 

PMID- 25875188
TI  - Magnetic nanoparticle thermometer: an investigation of minimum error transmission
      path and AC bias error.
AB  - The signal transmission module of a magnetic nanoparticle thermometer (MNPT) was
      established in this study to analyze the error sources introduced during the
      signal flow in the hardware system. The underlying error sources that
      significantly affected the precision of the MNPT were determined through
      mathematical modeling and simulation. A transfer module path with the minimum
      error in the hardware system was then proposed through the analysis of the
      variations of the system error caused by the significant error sources when the
      signal flew through the signal transmission module. In addition, a system
      parameter, named the signal-to-AC bias ratio (i.e., the ratio between the signal
      and AC bias), was identified as a direct determinant of the precision of the
      measured temperature. The temperature error was below 0.1 K when the signal-to-AC
      bias ratio was higher than 80 dB, and other system errors were not considered.
      The temperature error was below 0.1 K in the experiments with a commercial
      magnetic fluid (Sample SOR-10, Ocean Nanotechnology, Springdale, AR, USA) when
      the hardware system of the MNPT was designed with the aforementioned method. 

PMID- 25875189
TI  - Exploring direct 3D interaction for full horizontal parallax light field displays
      using leap motion controller.
AB  - This paper reports on the design and evaluation of direct 3D gesture interaction
      with a full horizontal parallax light field display. A light field display
      defines a visual scene using directional light beams emitted from multiple light
      sources as if they are emitted from scene points. Each scene point is rendered
      individually resulting in more realistic and accurate 3D visualization compared
      to other 3D displaying technologies. We propose an interaction setup combining
      the visualization of objects within the Field Of View (FOV) of a light field
      display and their selection through freehand gesture tracked by the Leap Motion
      Controller. The accuracy and usefulness of the proposed interaction setup was
      also evaluated in a user study with test subjects. The results of the study
      revealed high user preference for free hand interaction with light field display
      as well as relatively low cognitive demand of this technique. Further, our
      results also revealed some limitations and adjustments of the proposed setup to
      be addressed in future work. 

PMID- 25875190
TI  - Multi-camera and structured-light vision system (MSVS) for dynamic high-accuracy
      3D measurements of railway tunnels.
AB  - Railway tunnel 3D clearance inspection is critical to guaranteeing railway
      operation safety. However, it is a challenge to inspect railway tunnel 3D
      clearance using a vision system, because both the spatial range and field of view
      (FOV) of such measurements are quite large. This paper summarizes our work on
      dynamic railway tunnel 3D clearance inspection based on a multi-camera and
      structured-light vision system (MSVS). First, the configuration of the MSVS is
      described. Then, the global calibration for the MSVS is discussed in detail. The
      onboard vision system is mounted on a dedicated vehicle and is expected to suffer
      from multiple degrees of freedom vibrations brought about by the running vehicle.
      Any small vibration can result in substantial measurement errors. In order to
      overcome this problem, a vehicle motion deviation rectifying method is
      investigated. Experiments using the vision inspection system are conducted with
      satisfactory online measurement results. 

PMID- 25875191
TI  - Performance analysis on carrier phase-based tightly-coupled GPS/BDS/INS
      integration in GNSS degraded and denied environments.
AB  - The integration of Global Navigation Satellite Systems (GNSS) carrier phases with
      Inertial Navigation System (INS) measurements is essential to provide accurate
      and continuous position, velocity and attitude information, however it is
      necessary to fix ambiguities rapidly and reliably to obtain high accuracy
      navigation solutions. In this paper, we present the notion of combining the
      Global Positioning System (GPS), the BeiDou Navigation Satellite System (BDS) and
      low-cost micro-electro-mechanical sensors (MEMS) inertial systems for reliable
      navigation. An adaptive multipath factor-based tightly-coupled (TC) GPS/BDS/INS
      integration algorithm is presented and the overall performance of the integrated
      system is illustrated. A twenty seven states TC GPS/BDS/INS model is adopted with
      an extended Kalman filter (EKF), which is carried out by directly fusing
      ambiguity fixed double-difference (DD) carrier phase measurements with the INS
      predicted pseudoranges to estimate the error states. The INS-aided integer
      ambiguity resolution (AR) strategy is developed by using a dynamic model, a two
      step estimation procedure is applied with adaptively estimated covariance matrix
      to further improve the AR performance. A field vehicular test was carried out to
      demonstrate the positioning performance of the combined system. The results show
      the TC GPS/BDS/INS system significantly improves the single-epoch AR reliability
      as compared to that of GPS/BDS-only or single satellite navigation system
      integrated strategy, especially for high cut-off elevations. The AR performance
      is also significantly improved for the combined system with adaptive covariance
      matrix in the presence of low elevation multipath related to the GNSS-only case.
      A total of fifteen simulated outage tests also show that the time to relock of
      the GPS/BDS signals is shortened, which improves the system availability. The
      results also indicate that TC integration system achieves a few centimeters
      accuracy in positioning based on the comparison analysis and covariance analysis,
      even in harsh environments (e.g., in urban canyons), thus we can see the
      advantage of positioning at high cut-off elevations that the combined GPS/BDS
      brings. 

PMID- 25875192
TI  - A study of new pulse auscultation system.
AB  - This study presents a new type of pulse auscultation system, which uses a
      condenser microphone to measure pulse sound waves on the wrist, captures the
      microphone signal for filtering, amplifies the useful signal and outputs it to an
      oscilloscope in analog form for waveform display and storage and delivers it to a
      computer to perform a Fast Fourier Transform (FFT) and convert the pulse sound
      waveform into a heartbeat frequency. Furthermore, it also uses an audio signal
      amplifier to deliver the pulse sound by speaker. The study observed the
      principles of Traditional Chinese Medicine's pulsing techniques, where pulse
      signals at places called "cun", "guan" and "chi" of the left hand were measured
      during lifting (100 g), searching (125 g) and pressing (150 g) actions. Because
      the system collects the vibration sound caused by the pulse, the sensor itself is
      not affected by the applied pressure, unlike current pulse piezoelectric sensing
      instruments, therefore, under any kind of pulsing pressure, it displays pulse
      changes and waveforms with the same accuracy. We provide an acquired pulse and
      waveform signal suitable for Chinese Medicine practitioners' objective pulse
      diagnosis, thus providing a scientific basis for this Traditional Chinese
      Medicine practice. This study also presents a novel circuit design using an
      active filtering method. An operational amplifier with its differential features
      eliminates the interference from external signals, including the instant high
      frequency noise. In addition, the system has the advantages of simple circuitry,
      cheap cost and high precision. 

PMID- 25875193
TI  - Segmentation and tracking of anticyclonic eddies during a submarine volcanic
      eruption using ocean colour imagery.
AB  - The eruptive phase of a submarine volcano located 2 km away from the southern
      coast of El Hierro Island started on October 2011. This extraordinary event
      provoked a dramatic perturbation of the water column. In order to understand and
      quantify the environmental impacts caused, a regular multidisciplinary monitoring
      was carried out using remote sensing sensors. In this context, we performed the
      systematic processing of every MODIS and MERIS and selected high resolution
      Worldview-2 imagery to provide information on the concentration of a number of
      biological, physical and chemical parameters. On the other hand, the eruption
      provided an exceptional source of tracer that allowed the study a variety of
      oceanographic structures. Specifically, the Canary Islands belong to a very
      active zone of long-lived eddies. Such structures are usually monitored using sea
      level anomaly fields. However these products have coarse spatial resolution and
      they are not suitable to perform submesoscale studies. Thanks to the volcanic
      tracer, detailed studies were undertaken with ocean colour imagery allowing,
      using the diffuse attenuation coefficient, to monitor the process of
      filamentation and axisymmetrization predicted by theoretical studies and
      numerical modelling. In our work, a novel 2-step segmentation methodology has
      been developed. The approach incorporates different segmentation algorithms and
      region growing techniques. In particular, the first step obtains an initial eddy
      segmentation using thresholding or clustering methods and, next, the fine detail
      is achieved by the iterative identification of the points to grow and the
      subsequent application of watershed or thresholding strategies. The methodology
      has demonstrated an excellent performance and robustness and it has proven to
      properly capture the eddy and its filaments. 

PMID- 25875194
TI  - A online NIR sensor for the pilot-scale extraction process in Fructus aurantii
      coupled with single and ensemble methods.
AB  - Model performance of the partial least squares method (PLS) alone and bagging-PLS
      was investigated in online near-infrared (NIR) sensor monitoring of pilot-scale
      extraction process in Fructus aurantii. High-performance liquid chromatography
      (HPLC) was used as a reference method to identify the active pharmaceutical
      ingredients: naringin, hesperidin and neohesperidin. Several preprocessing
      methods and synergy interval partial least squares (SiPLS) and moving window
      partial least squares (MWPLS) variable selection methods were compared. Single
      quantification models (PLS) and ensemble methods combined with partial least
      squares (bagging-PLS) were developed for quantitative analysis of naringin,
      hesperidin and neohesperidin. SiPLS was compared to SiPLS combined with bagging
      PLS. Final results showed the root mean square error of prediction (RMSEP) of
      bagging-PLS to be lower than that of PLS regression alone. For this reason, an
      ensemble method of online NIR sensor is here proposed as a means of monitoring
      the pilot-scale extraction process in Fructus aurantii, which may also constitute
      a suitable strategy for online NIR monitoring of CHM. 

PMID- 25875195
TI  - Performance differences in year 1 of pioneer accountable care organizations.
AB  - BACKGROUND: In 2012, a total of 32 organizations entered the Pioneer accountable
      care organization (ACO) program, in which providers can share savings with
      Medicare if spending falls below a financial benchmark. Performance differences
      associated with characteristics of Pioneer ACOs have not been well described.
      METHODS: In a difference-in-differences analysis of Medicare fee-for-service
      claims, we compared Medicare spending for beneficiaries attributed to Pioneer
      ACOs (ACO group) with other beneficiaries (control group) before (2009 through
      2011) and after (2012) the start of Pioneer ACO contracts, with adjustment for
      geographic area and beneficiaries' sociodemographic and clinical characteristics.
      We estimated differential changes in spending for several subgroups of ACOs:
      those with and those without clear financial integration between hospitals and
      physician groups, those with higher and those with lower baseline spending, and
      the 13 ACOs that withdrew from the Pioneer program after 2012 and the 19 that did
      not. RESULTS: Adjusted Medicare spending and spending trends were similar in the
      ACO group and the control group during the precontract period. In 2012, the total
      adjusted per-beneficiary spending differentially changed in the ACO group as
      compared with the control group (-$29.2 per quarter, P=0.007), consistent with a
      1.2% savings. Savings were significantly greater for ACOs with baseline spending
      above the local average, as compared with those with baseline spending below the
      local average (P=0.05 for interaction), and for those serving high-spending
      areas, as compared with those serving low-spending areas (P=0.04). Savings were
      similar in ACOs with financial integration between hospitals and physician groups
      and those without, as well as in ACOs that withdrew from the program and those
      that did not. CONCLUSIONS: Year 1 of the Pioneer ACO program was associated with
      modest reductions in Medicare spending. Savings were greater for ACOs with higher
      baseline spending than for those with lower baseline spending and were unrelated
      to withdrawal from the program. (Funded by the National Institute on Aging and
      others.).

PMID- 25875196
TI  - Protection or harm? Suppressing substance-use data.

PMID- 25875197
TI  - Label-free screening of single biomolecules through resistive pulse sensing
      technology for precision medicine applications.
AB  - Employing integrated nano- and microfluidic circuits for detecting and
      characterizing biological compounds through resistive pulse sensing technology is
      a vibrant area of research at the interface of biotechnology and nanotechnology.
      Resistive pulse sensing platforms can be customized to study virtually any
      particle of choice which can be threaded through a fluidic channel and enable
      label-free single-particle interrogation with the primary read-out signal being
      an electric current fingerprint. The ability to perform label-free molecular
      screening with single-molecule and even single binding site resolution makes
      resistive pulse sensing technology a powerful tool for analyzing the smallest
      units of biological systems and how they interact with each other on a molecular
      level. This task is at the core of experimental systems biology and in particular
      'omics research which in combination with next-generation DNA-sequencing and next
      generation drug discovery and design forms the foundation of a novel disruptive
      medical paradigm commonly referred to as personalized medicine or precision
      medicine. DNA-sequencing has approached the 1000-Dollar-Genome milestone allowing
      for decoding a complete human genome with unmatched speed and at low cost.
      Increased sequencing efficiency yields massive amounts of genomic data. Analyzing
      this data in combination with medical and biometric health data eventually
      enables understanding the pathways from individual genes to physiological
      functions. Access to this information triggers fundamental questions for doctors
      and patients alike: what are the chances of an outbreak for a specific disease?
      Can individual risks be managed and if so how? Which drugs are available and how
      should they be applied? Could a new drug be tailored to an individual's genetic
      predisposition fast and in an affordable way? In order to provide answers and
      real-life value to patients, the rapid evolvement of novel computing approaches
      for analyzing big data in systems genomics has to be accompanied by an equally
      strong effort to develop next-generation DNA-sequencing and next-generation drug
      screening and design platforms. In that context lab-on-a-chip devices utilizing
      nanopore- and nanochannel based resistive pulse-sensing technology for DNA
      sequencing and protein screening applications occupy a key role. This paper
      describes the status quo of resistive pulse sensing technology for these two
      application areas with a special focus on current technology trends and
      challenges ahead. 

PMID- 25875198
TI  - Poor recognition of risk factors for hepatitis B by physicians prescribing
      immunosuppressive therapy: a call for universal rather than risk-based screening.
AB  - BACKGROUND: Reactivation of hepatitis B virus (HBV) during immunosuppressive
      therapy (IST) can lead to severe and even fatal hepatitis but can be largely
      prevented with prophylactic antiviral therapy. Screening for HBV prior to
      starting IST is recommended. Both risk-based and universal screening have been
      recommended by different societies. For effective risk-based screening,
      physicians must be aware of risk factors for chronic HBV infection. METHODS: The
      HBV screening practices prior to starting IST of rheumatologists, medical and
      hematological oncologists were evaluated by survey and chart review. Country of
      origin, the primary risk factor for HBV exposure, was determined in all patients.
      RESULTS: Of 140 rheumatology, 79 medical oncology and 53 hematology patients
      reviewed, 81%, 11% and 81% were deemed to be at high risk of HBV reactivation by
      their physicians respectively, however only 27%, 6% and 62% (p<0.0001) were
      actually screened for HBV prior to starting IST. For patients from HBV-endemic
      regions, more hematology patients (53%) were correctly identified by their
      physicians as being at high risk of reactivation than rheumatology patients
      (2.4%, p=0.0001) or medical oncology patients (15%, p=0.009). However actual
      screening rates were not increased in patients from endemic regions. A total of
      81 patients were screened for HBsAg; 2 were positive. Of the 33 patients screened
      for anti-HBc, 10 (30%) were positive. CONCLUSIONS: Hematologists, rheumatologists
      and medical oncologists had low rates of screening for HBV prior to prescribing
      IST, largely due to poor identification of those at risk for infection. Risk
      based screening strategies are unlikely to be effective and should be replaced by
      universal screening.

PMID- 25875199
TI  - Panic disorder and incident coronary heart disease: a systematic review and meta
      analysis protocol.
AB  - BACKGROUND: The clinical presentation of panic disorder and panic attack overlaps
      many symptoms typically experienced in coronary heart disease (CHD). Etiological
      links between panic disorder and CHD are controversial and remain largely
      tenuous. This systematic review aims to pool together data regarding panic
      disorder with respect to incident CHD or myocardial infarction. METHODS/DESIGN:
      Electronic databases (MEDLINE, EMBASE, PsycINFO and SCOPUS) will be searched
      using a search strategy exploding the topics for CHD and panic disorder. Authors
      and reference lists of included studies will also be contacted to identify
      additional published and unpublished studies. Eligibility criteria are as
      follows: POPULATION: persons without CHD who meet criteria for panic disorder,
      panic attack, anxiety neurosis or elevated panic disorder symptoms; Comparison:
      persons without CHD who do not meet criteria for panic disorder, panic attack,
      anxiety neurosis or elevated panic disorder symptoms; OUTCOME: verified fatal and
      non-fatal CHD at follow-up; including coronary revascularization procedure,
      coronary artery disease, and myocardial infarction. Studies adopting self-report
      CHD will be ineligible. Screening will be undertaken by two independent reviewers
      with disagreements resolved through discussion. Data extraction will include
      original data specified as hazard ratios, risk ratios, and original cell data if
      available. Risk of bias assessment will be undertaken by two independent
      reviewers. Meta-analytic methods will be used to synthesize the data collected
      relating to the CHD outcomes with Cochrane Review Manager 5.3. DISCUSSION: This
      systematic review aims to clarify whether panic disorder is associated with
      elevated risk for subsequent CHD. An evaluation of the etiological links between
      panic disorder with incident CHD might inform evidence-based clinical practice
      and policy concerning triaging chest pain patients, diagnostic assessment, and
      psychiatric intervention with panic disorder patients. SYSTEMATIC REVIEW
      REGISTRATION: PROSPERO CRD42014014891 .

PMID- 25875200
TI  - Subcutaneous and segmental fat loss with and without supportive supplements in
      conjunction with a low-calorie high protein diet in healthy women.
AB  - BACKGROUND: Weight loss benefits of multi-ingredient supplements in conjunction
      with a low-calorie, high-protein diet in young women are unknown. Therefore, the
      purpose of this study was to investigate the effects of a three-week low-calorie
      diet with and without supplementation on body composition. METHODS: Thirty-seven
      recreationally-trained women (n = 37; age = 27.1 +/- 4.2; height = 165.1 +/- 6.4;
      weight = 68.5 +/- 10.1; BMI = 25.1 +/- 3.4) completed one of the following three
      week interventions: no change in diet (CON); a high-protein, low-calorie diet
      supplemented with a thermogenic, conjugated linoleic acid (CLA), a protein gel,
      and a multi-vitamin (SUP); or the high-protein diet with isocaloric placebo
      supplements (PLA). Before and after the three-week intervention, body weight,
      %Fat via dual X-ray absorptiometry (DXA), segmental fat mass via DXA, %Fat via
      skinfolds, and skinfold thicknesses at seven sites were measured. RESULTS: SUP
      and PLA significantly decreased body weight (SUP: PRE, 70.47 +/- 8.01 kg to POST,
      67.51 +/- 8.10 kg; PLA: PRE, 67.88 +/- 12.28 kg vs. POST, 66.38 +/- 11.94 kg; p
      <= 0.05) with a greater (p <= 0.05) decrease in SUP than PLA or CON. SUP and PLA
      significantly decreased %Fat according to DXA (SUP: PRE, 34.98 +/- 7.05% to POST,
      32.99 +/- 6.89%; PLA: PRE, 34.22 +/- 6.36% vs. POST, 32.69 +/- 5.84%; p <= 0.05),
      whereas only SUP significantly decreased %Fat according to skinfolds (SUP: PRE,
      27.40 +/- 4.09% to POST, 24.08 +/- 4.31%; p <= 0.05). SUP significantly (p <=
      0.05) decreased thicknesses at five skinfolds (chest, waist, hip, subscapular,
      and tricep) compared to PLA, but not at two skinfolds (axilla and thigh).
      CONCLUSIONS: The addition of a thermogenic, CLA, protein, and a multi-vitamin to
      a three-week low-calorie diet improved weight loss, total fat loss and
      subcutaneous fat loss, compared to diet alone.

PMID- 25875201
TI  - Tsetse fly (G. f. fuscipes) distribution in the Lake Victoria basin of Uganda.
AB  - Tsetse flies transmit trypanosomes, the causative agent of human and animal
      African trypanosomiasis. The tsetse vector is extensively distributed across sub
      Saharan Africa. Trypanosomiasis maintenance is determined by the
      interrelationship of three elements: vertebrate host, parasite and the vector
      responsible for transmission. Mapping the distribution and abundance of tsetse
      flies assists in predicting trypanosomiasis distributions and developing rational
      strategies for disease and vector control. Given scarce resources to carry out
      regular full scale field tsetse surveys to up-date existing tsetse maps, there is
      a need to devise inexpensive means for regularly obtaining dependable area-wide
      tsetse data to guide control activities. In this study we used spatial
      epidemiological modelling techniques (logistic regression) involving 5000 field
      based tsetse-data (G. f. fuscipes) points over an area of 40,000 km2, with
      satellite-derived environmental surrogates composed of precipitation,
      temperature, land cover, normalised difference vegetation index (NDVI) and
      elevation at the sub-national level. We used these extensive tsetse data to
      analyse the relationships between presence of tsetse (G. f. fuscipes) and
      environmental variables. The strength of the results was enhanced through the
      application of a spatial autologistic regression model (SARM). Using the SARM we
      showed that the probability of tsetse presence increased with proportion of
      forest cover and riverine vegetation. The key outputs are a predictive tsetse
      distribution map for the Lake Victoria basin of Uganda and an improved
      understanding of the association between tsetse presence and environmental
      variables. The predicted spatial distribution of tsetse in the Lake Victoria
      basin of Uganda will provide significant new information to assist with the
      spatial targeting of tsetse and trypanosomiasis control. 

PMID- 25875202
TI  - Epigenetic modulations in activated cells early after HIV-1 infection and their
      possible functional consequences.
AB  - Epigenetic modifications refer to a number of biological processes which alter
      the structure of chromatin and its transcriptional activity such as DNA
      methylation and histone post-translational processing. Studies have tried to
      elucidate how the viral genome and its products are affected by epigenetic
      modifications imposed by cell machinery and how it affects the ability of the
      virus to either, replicate and produce a viable progeny or be driven to latency.
      The purpose of this study was to evaluate epigenetic modifications in PBMCs and
      CD4+ cells after HIV-1 infection analyzing three approaches: (i) global DNA-
      methylation; (ii) qPCR array and (iii) western blot. HIV-1 infection led to
      methylation increases in the cellular DNA regardless the activation status of
      PBMCs. The analysis of H3K9me3 and H3K27me3 suggested a trend towards
      transcriptional repression in activated cells after HIV-1 infection. Using a qPCR
      array, we detected genes related to epigenetic processes highly modulated in
      activated HIV-1 infected cells. SETDB2 and RSK2 transcripts showed highest up
      regulation levels. SETDB2 signaling is related to transcriptional silencing while
      RSK2 is related to either silencing or activation of gene expression depending on
      the signaling pathway triggered down-stream. In addition, activated cells
      infected by HIV-1 showed lower CD69 expression and a decrease of IL-2, IFN-gamma
      and metabolism-related factors transcripts indicating a possible functional
      consequence towards global transcriptional repression found in HIV-1 infected
      cells. Conversely, based on epigenetic markers studied here, non-stimulated cells
      infected by HIV-1, showed signs of global transcriptional activation. Our results
      suggest that HIV-1 infection exerts epigenetic modulations in activated cells
      that may lead these cells to transcriptional repression with important functional
      consequences. Moreover, non-stimulated cells seem to increase gene transcription
      after HIV-1 infection. Based on these observations, it is possible to speculate
      that the outcome of viral infections may be influenced by the cellular activation
      status at the moment of infection. 

PMID- 25875203
TI  - Proliferation rates of bovine primary muscle cells relate to liveweight and
      carcase weight in cattle.
AB  - Muscling in cattle is largely influenced by genetic background, ultimately
      affecting beef yield and is of major interest to the beef industry. This
      investigation aimed to determine whether primary skeletal muscle cells isolated
      from different breeds of cattle with a varying genetic potential for muscling
      differ in their myogenic proliferative capacity. Primary skeletal muscle cells
      were isolated and cultured from the Longissimus muscle (LM) of 6 month old Angus,
      Hereford and Wagyu X Angus cattle. Cells were assessed for rate of proliferation
      and gene expression of PAX7, MYOD, MYF5, and MYOG. Proliferation rates were found
      to differ between breeds of cattle whereby myoblasts from Angus cattle were found
      to proliferate at a greater rate than those of Hereford and Wagyu X Angus during
      early stages of growth (5-20 hours in culture) in vitro (P < 0.05). The
      proliferation rates of myoblasts during early stages of culture in vitro were
      also found to be positively related to the liveweight and carcase weight of
      cattle (P < 0.05). Gene expression of MYF5 was also found to be significantly
      down-regulated in WagyuX compared with Angus cattle (P < 0.05). These findings
      suggest that early events during myogenesis are important for determining
      liveweight and caracase weights in cattle. 

PMID- 25875205
TI  - Sources and levels of ambient ocean sound near the Antarctic Peninsula.
AB  - Arrays of hydrophones were deployed within the Bransfield Strait and Scotia Sea
      (Antarctic Peninsula region) from 2005 to 2009 to record ambient ocean sound at
      frequencies of up to 125 and 500 Hz. Icequakes, which are broadband, short
      duration signals derived from fracturing of large free-floating icebergs, are a
      prominent feature of the ocean soundscape. Icequake activity peaks during austral
      summer and is minimum during winter, likely following freeze-thaw cycles. Iceberg
      grounding and rapid disintegration also releases significant acoustic energy,
      equivalent to large-scale geophysical events. Overall ambient sound levels can be
      as much as ~10-20 dB higher in the open, deep ocean of the Scotia Sea compared to
      the relatively shallow Bransfield Strait. Noise levels become lowest during the
      austral winter, as sea-ice cover suppresses wind and wave noise. Ambient noise
      levels are highest during austral spring and summer, as surface noise, ice
      cracking and biological activity intensifies. Vocalizations of blue (Balaenoptera
      musculus) and fin (B. physalus) whales also dominate the long-term spectra
      records in the 15-28 and 89 Hz bands. Blue whale call energy is a maximum during
      austral summer-fall in the Drake Passage and Bransfield Strait when ambient noise
      levels are a maximum and sea-ice cover is a minimum. Fin whale vocalizations were
      also most common during austral summer-early fall months in both the Bransfield
      Strait and Scotia Sea. The hydrophone data overall do not show sustained
      anthropogenic sources (ships and airguns), likely due to low coastal traffic and
      the typically rough weather and sea conditions of the Southern Ocean. 

PMID- 25875204
TI  - Excess costs of comorbidities in chronic obstructive pulmonary disease: a
      systematic review.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a leading cause of
      morbidity and mortality worldwide. Comorbidities are often reported in patients
      with COPD and may influence the cost of care. Yet, the extent by which
      comorbidities affect costs remains to be determined. OBJECTIVES: To review,
      quantify and evaluate excess costs of comorbidities in COPD. METHODS: Using a
      systematic review approach, Pubmed and Embase were searched for studies analyzing
      excess costs of comorbidities in COPD. Resulting studies were evaluated according
      to study characteristics, comorbidity measurement and cost indicators. Mark-up
      factors were calculated for respective excess costs. Furthermore, a checklist of
      quality criteria was applied. RESULTS: Twelve studies were included. Nine
      evaluated comorbidity specific costs; three examined index-based results.
      Pneumonia, cardiovascular disease and diabetes were associated with the highest
      excess costs. The mark-up factors for respective excess costs ranged between 1.5
      and 2.5 in the majority of cases. On average the factors constituted a doubling
      of respective costs in the comorbid case. The main cost driver, among all
      studies, was inpatient cost. Indirect costs were not accounted for by the
      majority of studies. Study heterogeneity was high. CONCLUSIONS: The reviewed
      studies clearly show that comorbidities are associated with significant excess
      costs in COPD. The inclusion of comorbid costs and effects in future health
      economic evaluations of preventive or therapeutic COPD interventions seems highly
      advisable.

PMID- 25875206
TI  - Health state utility values for diabetic retinopathy: protocol for a systematic
      review and meta-analysis.
AB  - BACKGROUND: People with diabetic retinopathy tend to have lower levels of health
      related quality of life than individuals with no retinopathy. Strategies for
      screening and treatment have been shown to be cost-effective. In order to reduce
      the bias in cost-effectiveness estimates, systematic reviews of health state
      utility values (HSUVs) are crucial for health technology assessment and the
      development of decision analytic models. A review and synthesis of HSUVs for the
      different stages of disease progression in diabetic retinopathy has not
      previously been conducted. METHODS/DESIGN: We will conduct a systematic review of
      the available literature that reports HSUVs for people with diabetic retinopathy,
      in correspondence with current stage of disease progression and/or visual acuity.
      We will search Medline, EMBASE, Web of Science, Cost-Effectiveness Analysis
      Registry, Centre for Reviews and Dissemination Database, and EconLit to identify
      relevant English-language articles. Data will subsequently be synthesized using
      linear mixed effects modeling meta-regression. Additionally, reported disease
      severity classifications will be mapped to a four-level grading scale for
      diabetic retinopathy. DISCUSSION: The systematic review and meta-analysis will
      provide important evidence for future model-based economic evaluations of
      technologies for diabetic retinopathy. The meta-regression will enable the
      estimation of utility values at different disease stages for patients with
      particular characteristics and will also highlight where the design of the study
      and HSUV instrument have influenced the reported utility values. We believe this
      protocol to be the first of its kind to be published. SYSTEMATIC REVIEW
      REGISTRATION: PROSPERO CRD42014012891.

PMID- 25875207
TI  - Promoting healthy brain aging.

PMID- 25875208
TI  - Periodontal regeneration employing gingival margin-derived stem/progenitor cells
      in conjunction with IL-1ra-hydrogel synthetic extracellular matrix.
AB  - AIM: This study investigated the periodontal regenerative potential of gingival
      margin-derived stem/progenitor cells (G-MSCs) in conjunction with IL-1ra
      releasing hyaluronic acid synthetic extracellular matrix (HA-sECM). MATERIALS AND
      METHODS: Periodontal defects were induced at four sites in eight miniature pigs
      in the premolar/molar area (-4 weeks). Autologus G-MSCs were isolated from the
      free gingival margin and magnetically sorted, using anti-STRO-1 antibodies.
      Colony formation and multilineage differentiation potential were tested. The G
      MSCs were expanded and incorporated into IL-1ra-loaded/unloaded HA-sECM. Within
      every miniature pig, four periodontal defects were randomly treated with IL-1ra/G
      MSCs/HA-sECM (test group), G-MSCs/HA-sECM (positive-control), scaling and root
      planing (SRP; negative control-1) or left untreated (no-treatment group; negative
      control 2). Differences in clinical attachment level (DeltaCAL), probing depth
      (DeltaPD), gingival recession (DeltaGR), radiographic defect volume (DeltaRDV),
      and changes in bleeding on probing (BOP) between baseline and 16 weeks post
      transplantation, as well as periodontal attachment level (PAL), junctional
      epithelium length (JE), connective tissue adhesion (CTA), cementum regeneration
      (CR) and bone regeneration (BR) at 16 weeks post-transplantation were evaluated.
      RESULTS: Isolated G-MSCs showed stem/progenitor cell characteristics. IL-1ra
      loaded and unloaded G-MSCs/HA-sECM showed higher DeltaCAL, DeltaPD, DeltaGR, PAL,
      CR and BR as well as a lower JE compared to their negative controls and improved
      BOP. CONCLUSION: G-MSCs in conjunction with IL-1ra-loaded/unloaded HA-sECM show a
      significant periodontal regenerative potential.

PMID- 25875209
TI  - 6-Substituted sulfocoumarins are selective carbonic anhdydrase IX and XII
      inhibitors with significant cytotoxicity against colorectal cancer cells.
AB  - 6-Substituted sulfocoumarins bearing the carboxamido, trimethylammonium as well
      as the cyano and methoxy moieties with interesting inhibitory
      activity/selectivity against the tumor associated carbonic anhydrase (CA, EC
      4.2.1.1) isoforms hCA IX and XII are reported. Moieties leading to the best
      inhibition were tert-butylcarboxamido, phenylcarboxamido, and 4
      pyridylcarboxamido, with K(I) values of 2.1-8.1 nM. No inhibition of the off
      target hCA II and I was observed. A number of these compounds were evaluated
      against HT-29 colon cancer cell lines ex vivo. Compounds 9c and 9e revealed
      effective cytotoxic effects after 72 h of incubation in both normoxic and hypoxic
      conditions, unlike sulfonamide CA inhibitors that show such effects only in
      hypoxia. These results may be of particular importance for the choice of future
      drug candidates targeting hypoxic tumors and metastases, considering the fact
      that a sulfonamide CA IX inhibitor (SLC-0111) is presently in phase I clinical
      trials.

PMID- 25875210
TI  - Oscillatory brain activity reveals linguistic prints in the quantity code.
AB  - Number representations change through education, although it is currently unclear
      whether and how language could impact the magnitude representation that we share
      with other species. The most prominent view is that language does not play any
      role in modulating the core numeric representation involved in the contrast of
      quantities. Nevertheless, possible cultural hints on the numerical magnitude
      representation are currently on discussion focus. In fact, the acquisition of
      number words provides linguistic input that the quantity system may not ignore.
      Bilingualism offers a window to the study of this question, especially in
      bilinguals where the two number wording systems imply also two different
      numerical systems, such as in Basque-Spanish bilinguals. The present study
      evidences linguistic prints in the core number representational system through
      the analysis of EEG oscillatory activity during a simple number comparison task.
      Gamma band synchronization appears when Basque-Spanish bilinguals compare pairs
      of Arabic numbers linked through the Basque base-20 wording system, but it does
      not if the pairs are related through the base-10 system. Crucially, this gamma
      activity, originated in a left fronto-parietal network, only appears in
      bilinguals who learned math in Basque and not in equivalent proficiency
      bilinguals who learned math in Spanish. Thus, this neural index reflected in
      gamma band synchrony appears to be triggered by early learning experience with
      the base-20 numerical associations in Basque number words. 

PMID- 25875211
TI  - Modeling and predicting hemorrhagic fever with renal syndrome trends based on
      meteorological factors in Hu County, China.
AB  - BACKGROUND: Hu County is a serious hemorrhagic fever with renal syndrome (HFRS)
      epidemic area, with notable fluctuation of the HFRS epidemic in recent years.
      This study aimed to explore the optimal model for HFRS epidemic prediction in Hu.
      METHODS: Three models were constructed and compared, including a generalized
      linear model (GLM), a generalized additive model (GAM), and a principal
      components regression model (PCRM). The fitting and predictive adjusted R2 of
      each model were calculated. Ljung-Box Q tests for fitted and predicted residuals
      of each model were conducted. The study period was stratified into before (1971
      1993) and after (1994-2012) vaccine implementation epochs to avoid the
      confounding factor of vaccination. RESULTS: The autocorrelation of fitted and
      predicted residuals of the GAM in the two epochs were not significant (Ljung-Box
      Q test, P>.05). The adjusted R2 for the predictive abilities of the GLM, GAM, and
      PCRM were 0.752, 0.799, and 0.665 in the early epoch, and 0.669, 0.756, and 0.574
      in the recent epoch. The adjusted R2 values of the three models were lower in the
      early epoch than in the recent epoch. CONCLUSIONS: GAM is superior to GLM and
      PCRM for monthly HFRS case number prediction in Hu County. A shift in model
      reliability coincident with vaccination implementation demonstrates the
      importance of vaccination in HFRS control and prevention.

PMID- 25875212
TI  - Targeting the Gremlin-VEGFR2 axis - a promising strategy for multiple diseases?
AB  - Published recently in the Journal of Pathology, Lavoz et al. show that Gremlin
      promotes renal inflammation directly via VEGFR2. As Gremlin has been implicated
      in many other diseases, such as heart, lung and liver fibrosis, osteogenesis,
      angiogenesis and cancer, the new findings provide a rationale for novel concepts
      to investigate and potentially treat several pathologies.

PMID- 25875213
TI  - Dispersants have limited effects on exposure rates of oil spills on fish eggs and
      larvae in shelf seas.
AB  - Early life stages of fish are particularly vulnerable to oil spills. Simulations
      of overlap of fish eggs and larvae with oil from different oil-spill scenarios,
      both without and with the dispersant Corexit 9500, enable quantitative
      comparisons of dispersants as a mitigation alternative. We have used model
      simulations of a blow out of 4500 m(3) of crude oil per day (Statfjord light
      crude) for 30 days at three locations along the Norwegian coast. Eggs were
      released from nine different known spawning grounds, in the period from March 1st
      until the end of April, and all spawning products were followed for 90 days from
      the spill start at April first independent of time for spawning. We have modeled
      overlap between spawning products and oil concentrations giving a total
      polycyclic hydrocarbon (TPAH) concentration of more than 1.0 or 0.1 ppb (MUg/l).
      At these orders of magnitude, we expect acute mortality or sublethal effects,
      respectively. In general, adding dispersants results in higher concentrations of
      TPAHs in a reduced volume of water compared to not adding dispersants. Also, the
      TPAHs are displaced deeper in the water column. Model simulations of the spill
      scenarios showed that addition of chemical dispersant in general moderately
      decreased the fraction of eggs and larvae that were exposed above the selected
      threshold values. 

PMID- 25875214
TI  - Optical pendulum generator based on photomechanical liquid-crystalline actuators.
AB  - For converting light energy into electricity, an optical pendulum generator was
      designed by combining photomechanical movement of liquid-crystalline actuator
      (LCA) with Faraday's law of electromagnetic induction. Bilayer cantilever
      actuators were first fabricated with LDPE and LCA. Their photomechanical movement
      drove the attached copper coils to cut magnetic line of force generating
      electricity. The output electricity was proportional to the changing rate of the
      magnetic flux, which was greatly influenced by light intensity, film thickness,
      and sample size. Continuous electrical output was also achieved. This simple
      strategy may expand applications of photoactive materials in the capture and
      storage of light energy. 

PMID- 25875215
TI  - The phenotypic spectrum of organic acidurias and urea cycle disorders. Part 1:
      the initial presentation.
AB  - BACKGROUND: The clinical presentation of patients with organic acidurias (OAD)
      and urea cycle disorders (UCD) is variable; symptoms are often non-specific.
      AIMS/METHODS: To improve the knowledge about OAD and UCD the E-IMD consortium
      established a web-based patient registry. RESULTS: We registered 795 patients
      with OAD (n = 452) and UCD (n = 343), with ornithine transcarbamylase (OTC)
      deficiency (n = 196), glutaric aciduria type 1 (GA1; n = 150) and methylmalonic
      aciduria (MMA; n = 149) being the most frequent diseases. Overall, 548 patients
      (69 %) were symptomatic. The majority of them (n = 463) presented with acute
      metabolic crisis during (n = 220) or after the newborn period (n = 243)
      frequently demonstrating impaired consciousness, vomiting and/or muscular
      hypotonia. Neonatal onset of symptoms was most frequent in argininosuccinic
      synthetase and lyase deficiency and carbamylphosphate 1 synthetase deficiency,
      unexpectedly low in male OTC deficiency, and least frequently in GA1 and female
      OTC deficiency. For patients with MMA, propionic aciduria (PA) and OTC deficiency
      (male and female), hyperammonemia was more severe in metabolic crises during than
      after the newborn period, whereas metabolic acidosis tended to be more severe in
      MMA and PA patients with late onset of symptoms. Symptomatic patients without
      metabolic crises (n = 94) often presented with a movement disorder, mental
      retardation, epilepsy and psychiatric disorders (the latter in UCD only).
      CONCLUSIONS: The initial presentation varies widely in OAD and UCD patients. This
      is a challenge for rapid diagnosis and early start of treatment. Patients with a
      sepsis-like neonatal crisis and those with late-onset of symptoms are both at
      risk of delayed or missed diagnosis.

PMID- 25875217
TI  - Untargeted metabolomic analysis for the clinical screening of inborn errors of
      metabolism.
AB  - Global metabolic profiling currently achievable by untargeted mass spectrometry
      based metabolomic platforms has great potential to advance our understanding of
      human disease states, including potential utility in the detection of novel and
      known inborn errors of metabolism (IEMs). There are few studies of the technical
      reproducibility, data analysis methods, and overall diagnostic capabilities when
      this technology is applied to clinical specimens for the diagnosis of IEMs. We
      explored the clinical utility of a metabolomic workflow capable of routinely
      generating semi-quantitative z-score values for ~900 unique compounds, including
      ~500 named human analytes, in a single analysis of human plasma. We tested the
      technical reproducibility of this platform and applied it to the retrospective
      diagnosis of 190 individual plasma samples, 120 of which were collected from
      patients with a confirmed IEM. Our results demonstrate high intra-assay precision
      and linear detection for the majority compounds tested. Individual metabolomic
      profiles provided excellent sensitivity and specificity for the detection of a
      wide range of metabolic disorders and identified novel biomarkers for some
      diseases. With this platform, it is possible to use one test to screen for dozens
      of IEMs that might otherwise require ordering multiple unique biochemical tests.
      However, this test may yield false negative results for certain disorders that
      would be detected by a more well-established quantitative test and in its current
      state should be considered a supplementary test. Our findings describe a novel
      approach to metabolomic analysis of clinical specimens and demonstrate the
      clinical utility of this technology for prospective screening of IEMs. 

PMID- 25875218
TI  - Simplification of Caribbean reef-fish assemblages over decades of coral reef
      degradation.
AB  - Caribbean coral reefs are becoming structurally simpler, largely due to human
      impacts. The consequences of this trend for reef-associated communities are
      currently unclear, but expected to be profound. Here, we assess whether changes
      in fish assemblages have been non-random over several decades of declining reef
      structure. More specifically, we predicted that species that depend exclusively
      on coral reef habitat (i.e., habitat specialists) should be at a disadvantage
      compared to those that use a broader array of habitats (i.e., habitat
      generalists). Analysing 3727 abundance trends of 161 Caribbean reef-fishes,
      surveyed between 1980 and 2006, we found that the trends of habitat-generalists
      and habitat-specialists differed markedly. The abundance of specialists started
      to decline in the mid-1980s, reaching a low of ~60% of the 1980 baseline by the
      mid-1990s. Both the average and the variation in abundance of specialists have
      increased since the early 2000s, although the average is still well below the
      baseline level of 1980. This modest recovery occurred despite no clear evidence
      of a regional recovery in coral reef habitat quality in the Caribbean during the
      2000s. In contrast, the abundance of generalist fishes remained relatively stable
      over the same three decades. Few specialist species are fished, thus their
      population declines are most likely linked to habitat degradation. These results
      mirror the observed trends of replacement of specialists by generalists, observed
      in terrestrial taxa across the globe. A significant challenge that arises from
      our findings is now to investigate if, and how, such community-level changes in
      fish populations affect ecosystem function. 

PMID- 25875219
TI  - Transition-metal-free benzannulation for diverse and polyfunctionalized biaryl
      formation.
AB  - A novel and efficient synthesis of highly functionalized and diverse biaryls via
      mild base-promoted transition-metal-free benzannulation was achieved in good
      yield from readily available beta-ketoesters, beta-ketoamides, or 1,3-diketones
      with cinnamaldehydes or aryl aldehydes. This transformation comprises a sequence
      of the formation of three new bonds through multicomponent reactions as a one-pot
      procedure. This novel biaryl formation proceeds through domino Michael
      addition/intramolecular and intermolecular aldol/[1,5]-hydrogen
      shift/tautomerization. This protocol provides a great advantage in introducing
      various functional groups on the aromatic ring of biaryls. 

PMID- 25875216
TI  - The phenotypic spectrum of organic acidurias and urea cycle disorders. Part 2:
      the evolving clinical phenotype.
AB  - BACKGROUND: The disease course and long-term outcome of patients with organic
      acidurias (OAD) and urea cycle disorders (UCD) are incompletely understood. AIMS:
      To evaluate the complex clinical phenotype of OAD and UCD patients at different
      ages. RESULTS: Acquired microcephaly and movement disorders were common in OAD
      and UCD highlighting that the brain is the major organ involved in these
      diseases. Cardiomyopathy [methylmalonic (MMA) and propionic aciduria (PA)],
      prolonged QTc interval (PA), optic nerve atrophy [MMA, isovaleric aciduria
      (IVA)], pancytopenia (PA), and macrocephaly [glutaric aciduria type 1 (GA1)] were
      exclusively found in OAD patients, whereas hepatic involvement was more frequent
      in UCD patients, in particular in argininosuccinate lyase (ASL) deficiency.
      Chronic renal failure was often found in MMA, with highest frequency in mut(0)
      patients. Unexpectedly, chronic renal failure was also observed in adolescent and
      adult patients with GA1 and ASL deficiency. It had a similar frequency in
      patients with or without a movement disorder suggesting different
      pathophysiology. Thirteen patients (classic OAD: 3, UCD: 10) died during the
      study interval, ten of them during the initial metabolic crisis in the newborn
      period. Male patients with late-onset ornithine transcarbamylase deficiency were
      presumably overrepresented in the study population. CONCLUSIONS: Neurologic
      impairment is common in OAD and UCD, whereas the involvement of other organs
      (heart, liver, kidneys, eyes) follows a disease-specific pattern. The
      identification of unexpected chronic renal failure in GA1 and ASL deficiency
      emphasizes the importance of a systematic follow-up in patients with rare
      diseases.

PMID- 25875220
TI  - Curcumin attenuates urinary excretion of albumin in type II diabetic patients
      with enhancing nuclear factor erythroid-derived 2-like 2 (Nrf2) system and
      repressing inflammatory signaling efficacies.
AB  - Curcumin has a therapeutic potential in treating diabetic kidney disease (DKD)
      while potential mechanisms underlining this beneficial effect remain to be
      elucidated. In the present study, curcumin intervention was performed in patients
      with Type II diabetes mellitus (T2DM) by oral intake of curcumin at the dose of
      500 mg/day for a period of 15-30 days. Nephritic excretion of urinary micro
      albumin (U-mAlb) and blood metabolic indexes were assessed before and after this
      intervention. In addition, the lipid oxidation index, malondialdehyde (MDA) in
      plasma and the status of anti-oxidative Nrf2 system in blood lymphocytes were
      measured. The effect of curcumin on inflammation was assessed by measuring plasma
      lipopolysaccharide (LPS) content and inflammatory signaling protein in blood
      lymphocytes. A self-comparison method was used for assessing statistical
      significances of these measurements. Here we show that curcumin intervention
      markedly attenuated U-mAlb excretion without affecting metabolic control of
      participated patients. In addition, curcumin reduced plasma MDA level with
      enhanced the Nrf2 system specifically regulated protein, NAD(P)H quinone
      oxidoreductase 1 (NQO-1) together with other anti-oxidative enzymes in patients'
      blood lymphocytes. Furthermore, we observed reduced plasma LPS content and
      increased IkappaB, an inhibitory protein on inflammatory signaling in patient's
      lymphocytes after curcumin administration. Finally, several gut bacterials
      important for maintaining gut barrier integrity and function were upregulated by
      curcumin.In conclusion, short-term curcumin intervention ablates DKD progress
      with activating Nrf2 anti-oxidative system and anti-inflammatory efficacies in
      patients with T2DM. 

PMID- 25875221
TI  - A short synthesis of (+/-)-antroquinonol in an unusual scaffold of 4-hydroxy-2
      cyclohexenone.
AB  - Antroquinonol, which was first isolated from a mushroom, Antrodia cinnamomea,
      found in Taiwan, is an anticancer compound with a unique core structure of 4
      hydroxy-2,3-dimethoxycyclohex-2-enone carrying methyl, farnesyl and hydroxyl
      substituents in the 4,5-cis-5,6-trans configuration. A short synthesis of (+/-)
      antroquinonol is accomplished in seven steps from 2,3,4-trimethoxyphenol, which
      is oxidized in methanol to a highly electron-rich substrate of 2,3,4,4
      tetramethoxycyclohexadienone and then a Michael reaction with dimethylcuprate is
      performed as the key step, followed by alkylation, reduction and epimerization to
      incorporate the required substituents at three contiguous stereocenters. 

PMID- 25875222
TI  - Suicidality in obsessive compulsive disorder (OCD): a systematic review and meta
      analysis.
AB  - Although a growing number of studies have examined the frequency of suicidal
      thoughts and behaviors in individuals with obsessive compulsive disorder (OCD),
      there is controversy about the frequency and burden of suicidality in OCD. This
      is the first systematic review aimed at examining the association between
      suicidality and OCD and at providing evidence about psychological mechanisms that
      may underlie suicidality in those with OCD. Five electronic bibliographic
      databases were searched up to April 2014: Medline, PsycINFO, Embase, Web of
      Science and CINAHL. Meta-analysis using random effects models was conducted.
      Forty-eight studies were included in the systematic review. The pooled effect
      size across 30 independent comparisons revealed a moderate to high, significant
      association between suicidality and OCD (Hedges' g=0.66, 95% confidence interval
      0.49-0.82) which persisted across different types of suicidality including
      suicidal ideation and suicide attempts. Comorbid Axis I disorders, increased
      severity of comorbid depressive and anxiety symptoms, increased severity of
      obsessions, feelings of hopelessness and past history of suicide attempts were
      associated with worsening levels of suicidality in OCD. There was no indication
      for publication bias but the methodological quality of the studies was low. The
      theoretical, research and clinical implications of these findings are emphasized.

PMID- 25875223
TI  - Anatomical-based model for simulation of HIFU-induced lesions in atherosclerotic
      plaques.
AB  - PURPOSE: The aim of this study was to simulate the effect of high intensity
      focused ultrasound (HIFU) in non-homogenous medium for targeting atherosclerotic
      plaques in vivo. MATERIALS AND METHODS: A finite-difference time-domain
      heterogeneous model for acoustic and thermal tissue response in the treatment
      region was derived from ultrasound images of the treatment region. A 3.5 MHz dual
      mode ultrasound array suitable for targeting peripheral vessels was used. The
      array has a lateral and elevation focus at 40 mm with fenestration in its centre
      through which a 7.5 MHz diagnostic transducer can be placed. Two cases were
      simulated where seven adjacent HIFU shots (~5000 W/cm2, 2-s exposure time) were
      targeted on the plaque tissue within the femoral artery. The transient bioheat
      equation with a convective term to account for blood flow was used to predict the
      thermal dose. The results of the simulation model were then validated against the
      histology data. RESULTS: The simulation model predicted the HIFU-induced damage
      for both cases, and correlated well with the histology data. For the first case
      thermal damage was detected within the targeted plaque, while for the second case
      thermal damage was detected in the pre-focal region. CONCLUSION: The results
      suggest that a realistic, image-based acoustic and thermal model of the treatment
      region is capable of predicting the extent of thermal damage to target plaque
      tissue. The model considered the effect of the wall thickness of large arteries
      and the heat-sink effect of flowing blood. The model is used for predicting the
      size and pattern of HIFU damage in vivo.

PMID- 25875224
TI  - Development of a novel method to enhance the therapeutic effect on tumours by
      simultaneous action of radiation and heating.
AB  - PURPOSE: This paper describes the development of a new type of electromagnetic
      hyperthermia applicator delivering dose control within large application fields
      and increased effectiveness by providing simultaneous action of radiation and
      heating (SRH) in malignant tumours, and development of a dosimetric feedback
      method to support SRH. MATERIALS AND METHODS: Single and phased arrays of
      flexible applicators have been developed to allow simultaneous hyperthermia and
      external beam therapy. A frequency of 434 MHz is used to heat near-surface and
      moderately deep-seated tumours and 70 MHz for deep-seated tumours. Phase and
      amplitude control allows focusing of electromagnetic energy (EM) to deep-seated
      tumours. The specific absorption rate (SAR) dose distribution can be modified to
      achieve uniform heating of tumours with complex shapes and heterogeneous tissue
      properties. A lithium fluoride thermoluminescent dosimeter (TLD) in a flexible
      film cassette has been developed for real-time dose measurement. RESULTS: Four
      types of 434 MHz applicators were manufactured with 3, 4, 9 or 12 independent
      applicators. Two types of 70 MHz applicators were made with 4 or 6 independent
      applicators. Phantom tests demonstrated the ability to control the SAR pattern by
      phase and amplitude control. Placement of the dosimeter between bolus and phantom
      increased the phantom surface temperature up to 3  degrees C and showed that the
      ratio of absorbed energy in TLD to dose in water approaches (0.83 +/- 3%) for
      photon energies >60 keV. CONCLUSIONS: Simultaneous and controlled radiation and
      local hyperthermia is technically feasible in a preclinical setting, a clinical
      feasibility test is the next step.

PMID- 25875225
TI  - Single photon detector with high polarization sensitivity.
AB  - Polarization is one of the key parameters of light. Most optical detectors are
      intensity detectors that are insensitive to the polarization of light. A
      superconducting nanowire single photon detector (SNSPD) is naturally sensitive to
      polarization due to its nanowire structure. Previous studies focused on producing
      a polarization-insensitive SNSPD. In this study, by adjusting the width and pitch
      of the nanowire, we systematically investigate the preparation of an SNSPD with
      high polarization sensitivity. Subsequently, an SNSPD with a system detection
      efficiency of 12% and a polarization extinction ratio of 22 was successfully
      prepared. 

PMID- 25875226
TI  - Long-term prescription of alpha-blockers decrease the risk of recurrent
      urolithiasis needed for surgical intervention-a nationwide population-based
      study.
AB  - PURPOSE: alpha1 receptors and subtypes have been confirmed to distribute in human
      pelvis and calyces recently. As used in ureteral stones, alpha-blocker treatment
      may facilitate kidney stone passage and long-term prescription of alpha-blocker
      may decrease the risk of recurrent urolithiasis. The aim of this study is to
      determine if use of alpha-blockers 180 days or more can decrease the risk of
      recurrent urolithiasis needed for surgical intervention. MATERIALS AND METHODS: A
      representative database of 1,000,000 patients from Taiwan's National Health
      Insurance was analyzed. Eligible patients were those who had received the first
      time procedure for upper urinary stone removal, including extracorporeal shock
      wave lithotripsy, ureterorenoscopic lithotripsy, or both, between 2000 and 2010.
      After completing a 180-day treatment for first event, patients were prospectively
      followed-up until a second set of stone procedures was performed (proxy of stone
      recurrence), loss to follow-up, or end of study. The effect of percentage of
      total number of days of alpha-blocker use on need for second set of stone
      procedures within a post treatment 180-day follow-up period was analyzed by
      quartile. A nested case-control study was also performed. RESULTS: 1,259 patients
      were eligible for final analyses. During 3,980 person-years follow-up, 167
      patients had recurrent urolithiasis needed for surgical intervention. From first
      to fourth quartile of drug exposure, recurrence rates were 45.64, 47.19, 43.11,
      and 18.52 per 1,000 person-years. The adjusted hazard ratio was 0.46 (95% CI =
      0.24 to 0.89) for the fourth quartile (vs. quartile 1). In the nested case
      control study, adjusted ORs was 0.23 (95% CI = 0.10 to 0.53) in the fourth
      quartile (vs. quartile 1). The results remained similar even in patients
      categorized by cumulative defined daily dose (cDDD) quartiles and average cDDD
      per day quartiles. CONCLUSION: Use of alpha-blockers for 180 days or more
      decrease the risk of recurrent urolithiasis needed for surgical intervention. In
      patients at higher risk of recurrent urolithiasis, long term prescription of
      alpha-blockers might help them prevent further surgical intervention.

PMID- 25875227
TI  - Experiences with PMMA cement as a stand-alone intervertebral spacer: Percutaneous
      cement discoplasty in the case of vacuum phenomenon within lumbar intervertebral
      discs.
AB  - BACKGROUND: The treatment of symptomatic degenerative disc disease of the lumbar
      spine in elderly patients by standard surgical methods is often limited due to
      severe comorbidities (e.g., cardiopulmonary disease, hypertonia, diabetes).
      Minimally invasive procedures are more acceptable in this population, since they
      reduce surgical morbidity and the risk of complications. The percutaneous cement
      discoplasty (PCD) technique was introduced by the authors to treat dynamic (and
      angular) instability of the symptomatic lumbar segment by injecting bone cement
      (polymethylmethacrylate, PMMA) into the disc spaces showing vacuum phenomena via
      a posterolaterally positioned Jamshidi needle. The aim of this article is to
      describe the indication, method, and clinical results of PCD. METHOD: A total of
      81 patients were treated with PCD in a tertiary care referral center over a 6
      year period. The current study includes the first group of 47 consecutive
      patients to complete a pre- and postoperative questionnaire booklet regarding leg
      and back pain using the visual analog scale (VAS) and the Oswestry disability
      index (ODI) questionnaire. RESULTS: A total of 130 discs in these 47 patients
      were treated with PCD. The majority of patients reported a reduction in their
      lower back and leg pain (69% and 66%, respectively; p < 0.02) postoperatively. At
      6-month follow-up, 61% of patients had a minimum 10-point reduction in their ODI
      scores (p < 0.01). CONCLUSION: Elderly patients with symptomatic dynamic
      foraminal stenosis and vacuum phenomenon in the intervertebral disc are suitable
      candidates for PCD, particularly if they represent high-risk patients for open
      surgery.

PMID- 25875228
TI  - The importance of soft tissue stabilization in trans-femoral amputation : English
      version.
AB  - Transfemoral amputations with more proximal amputation levels have the problem of
      secondary development into flexion and abduction contractures. This is induced by
      muscle imbalance, especially the loss of adductor muscle insertions when abductor
      muscle insertions are preserved. This causes considerable problems when fitting
      prosthetics. Myodesis with insertion of the distally detached adductor magnus
      muscle to the lateral femoral cortex, introduced here, results in a stronger
      stump with good muscle balance, and prosthetics fitting is significantly
      improved. 

PMID- 25875229
TI  - Fungi identify the geographic origin of dust samples.
AB  - There is a long history of archaeologists and forensic scientists using pollen
      found in a dust sample to identify its geographic origin or history. Such
      palynological approaches have important limitations as they require time
      consuming identification of pollen grains, a priori knowledge of plant species
      distributions, and a sufficient diversity of pollen types to permit spatial or
      temporal identification. We demonstrate an alternative approach based on DNA
      sequencing analyses of the fungal diversity found in dust samples. Using nearly
      1,000 dust samples collected from across the continental U.S., our analyses
      identify up to 40,000 fungal taxa from these samples, many of which exhibit a
      high degree of geographic endemism. We develop a statistical learning algorithm
      via discriminant analysis that exploits this geographic endemicity in the fungal
      diversity to correctly identify samples to within a few hundred kilometers of
      their geographic origin with high probability. In addition, our statistical
      approach provides a measure of certainty for each prediction, in contrast with
      current palynology methods that are almost always based on expert opinion and
      devoid of statistical inference. Fungal taxa found in dust samples can therefore
      be used to identify the origin of that dust and, more importantly, we can
      quantify our degree of certainty that a sample originated in a particular place.
      This work opens up a new approach to forensic biology that could be used by
      scientists to identify the origin of dust or soil samples found on objects,
      clothing, or archaeological artifacts. 

PMID- 25875230
TI  - Projected shifts in Coffea arabica suitability among major global producing
      regions due to climate change.
AB  - Regional studies have shown that climate change will affect climatic suitability
      for Arabica coffee (Coffea arabica) within current regions of production.
      Increases in temperature and changes in precipitation patterns will decrease
      yield, reduce quality and increase pest and disease pressure. This is the first
      global study on the impact of climate change on suitability to grow Arabica
      coffee. We modeled the global distribution of Arabica coffee under changes in
      climatic suitability by 2050s as projected by 21 global circulation models. The
      results suggest decreased areas suitable for Arabica coffee in Mesoamerica at
      lower altitudes. In South America close to the equator higher elevations could
      benefit, but higher latitudes lose suitability. Coffee regions in Ethiopia and
      Kenya are projected to become more suitable but those in India and Vietnam to
      become less suitable. Globally, we predict decreases in climatic suitability at
      lower altitudes and high latitudes, which may shift production among the major
      regions that produce Arabica coffee. 

PMID- 25875232
TI  - Optimal timing for type C3 thoracic fractures with posterior surgical approach: a
      retrospective cohort study.
AB  - BACKGROUND: Type C3 thoracic fracture is a severe spinal injury, but one that is
      clinically rare, and there are few reports pertaining to the treatment of this
      type of fracture. No consensus has been achieved on the proper timing of spine
      fracture fixation; therefore, we focused on evaluating the surgical effects using
      a posterior approach and determining the influence of surgical timing on surgical
      outcomes. METHODS: This was a retrospective cohort study of 36 cases of type C3
      thoracic fracture in patients admitted to the hospital from April 2005 to October
      2012, and who were divided into two groups according to the timing of surgery:
      early fixation (<72 h) and late fixation (>72 h). Surgical outcomes were analyzed
      based on surgery duration, intraoperative blood loss, intensive care unit and
      hospital stay, mortality rate, and complications. RESULTS: There were 13 patients
      in the early fixation group and 23 patients in the late fixation group. Patients
      were treated with posterior decompression, intervertebral titanium mesh support,
      pedicle screw fixation, and fusion. All fractures involved a single segment:
      T7/T8 (8 patients), T9/T10 (11 patients), and T11/T12 (17 patients). All injuries
      were classified as American Spinal Injury Association (ASIA) grade A. Patients
      underwent periodic follow-up over a period of 12-30 months (average, 22.5
      months). One patient developed ascending myelitis and died of respiratory failure
      1 month after early fixation, and two patients died of pulmonary infection after
      late fixation procedures. Other patients achieved bone fusion without improvement
      in ASIA grade. No statistically significant difference in parameters was observed
      between groups. CONCLUSIONS: Though type C3 thoracic fracture is one of the most
      severe spinal injuries, complete reduction and recovery of spinal stability can
      be achieved using a posterior approach. As clinical outcomes in this study were
      similar between early and late fixation procedures, early surgical intervention
      may not be helpful for improving neurologic recovery in type C3 thoracic
      fractures.

PMID- 25875231
TI  - Unraveling the molecular signatures of oxidative phosphorylation to cope with the
      nutritionally changing metabolic capabilities of liver and muscle tissues in
      farmed fish.
AB  - Mitochondrial oxidative phosphorylation provides over 90% of the energy produced
      by aerobic organisms, therefore the regulation of mitochondrial activity is a
      major issue for coping with the changing environment and energy needs. In fish,
      there is a large body of evidence of adaptive changes in enzymatic activities of
      the OXPHOS pathway, but less is known at the transcriptional level and the first
      aim of the present study was to define the molecular identity of the actively
      transcribed subunits of the mitochondrial respiratory chain of a livestock
      animal, using gilthead sea bream as a model of farmed fish with a high added
      value for European aquaculture. Extensive BLAST searches in our transcriptomic
      database (www.nutrigroup-iats.org/seabreamdb) yielded 97 new sequences with a
      high coverage of catalytic, regulatory and assembly factors of Complex I to V.
      This was the basis for the development of a PCR array for the simultaneous
      profiling of 88 selected genes. This new genomic resource allowed the
      differential gene expression of liver and muscle tissues in a model of 10 fasting
      days. A consistent down-regulated response involving 72 genes was made by the
      liver, whereas an up-regulated response with 29 and 10 differentially expressed
      genes was found in white skeletal muscle and heart, respectively. This
      differential regulation was mostly mediated by nuclear-encoded genes (skeletal
      muscle) or both mitochondrial- and nuclear-encoded genes (liver, heart), which is
      indicative of a complex and differential regulation of mitochondrial and nuclear
      genomes, according to the changes in the lipogenic activity of liver and the
      oxidative capacity of glycolytic and highly oxidative muscle tissues. These
      insights contribute to the identification of the most responsive elements of
      OXPHOS in each tissue, which is of relevance for the appropriate gene targeting
      of nutritional and/or environmental metabolic disturbances in livestock animals. 

PMID- 25875234
TI  - Confronting AIDS-related loss and grief: an exploratory study of professional
      caregivers in KwaZulu-Natal, South Africa.
AB  - As a result of the high mortality rate associated with AIDS, professional
      caregivers witness ongoing loss among clients. Besides finding ways to assist the
      dying and the bereaved, caregivers must cope with their own feelings surrounding
      loss. The purpose of this descriptive exploratory study is to examine caregivers'
      perceptions of the impact of AIDS-related deaths on clients, caregivers'
      experiences helping bereaved clients, caregivers' own feelings about dealing with
      AIDS-related loss, and other aspects of their job. In-depth interviews were
      conducted separately with eight caregivers employed in programmes with various
      organisations serving people infected or affected by HIV/AIDS in KwaZulu-Natal,
      South Africa. Caregivers expressed difficulty in assisting clients with their
      grief due to several factors, including more-pressing client needs (such as
      economic survival), clients' reticence to talk about their grief, inadequate
      preparation for dealing with death and bereavement as professionals, and scarce
      organisational resources. Exposure to ongoing loss was very difficult for
      caregivers, and, despite the rewards associated with HIV/AIDS work, several that
      I interviewed could not foresee working in this field much longer. 

PMID- 25875235
TI  - The power of AIDS: kinship, mobility and the valuing of social and ritual
      relationships in Tanzania.
AB  - The HIV/AIDS epidemic in Africa has become a test case of the effects of
      globalisation, in that it demonstrates how international processes may affect
      regional life situations and how 'the local' can simultaneously develop in its
      own way, through the processes of appropriating, modifying, and resisting global
      influences. Drawing on fieldwork in Tanzania, I show how the Luo in the Mara
      region define HIV/AIDS as an outcome of modernity and globalisation, which to
      them have become embodied in processes of migration, the collapse of generational
      and gender hierarchies, and an increased immorality in contemporary society.
      While social and moral ruptures in Mara become further condensed in tensions
      between lineages and AIDS-sick relatives, mourning and burial rituals (including
      widow cleansing), disputes over inheritance rights, and the attribution of
      illness to the breaking of a taboo (chira) have become essential for negotiating
      and maintaining social and cultural relationships in an era of AIDS. In
      conclusion I argue that the concepts of vitality and moral practice may assist an
      understanding of how different social actors in sub-Saharan Africa have responded
      to the breakdowns associated with increased suffering and death, and to describe
      some social and moral developments observable in the context of internationally
      driven public health campaigns in the region. 

PMID- 25875233
TI  - Spatio-temporal regulation of the human licensing factor Cdc6 in replication and
      mitosis.
AB  - To maintain genome stability, the thousands of replication origins of mammalian
      genomes must only initiate replication once per cell cycle. This is achieved by a
      strict temporal separation of ongoing replication in S phase, and the formation
      of pre-replicative complexes in the preceding G1 phase, which "licenses" each
      origin competent for replication. The contribution of the loading factor Cdc6 to
      the timing of the licensing process remained however elusive due to seemingly
      contradictory findings concerning stabilization, degradation and nuclear export
      of Cdc6. Using fluorescently tagged Cdc6 (Cdc6-YFP) expressed in living cycling
      cells, we demonstrate here that Cdc6-YFP is stable and chromatin-associated
      during mitosis and G1 phase. It undergoes rapid proteasomal degradation during S
      phase initiation followed by active export to the cytosol during S and G2 phases.
      Biochemical fractionation abolishes this nuclear exclusion, causing aberrant
      chromatin association of Cdc6-YFP and, likely, endogenous Cdc6, too. In addition,
      we demonstrate association of Cdc6 with centrosomes in late G2 and during
      mitosis. These results show that multiple Cdc6-regulatory mechanisms coexist but
      are tightly controlled in a cell cycle-specific manner. 

PMID- 25875236
TI  - Talking about sex in Botswana: social desirability bias and possible implications
      for HIV-prevention research.
AB  - Evaluations of the safety, effectiveness, and feasibility of HIV prevention
      interventions rely on self-reported sexual behaviour data. The accuracy of such
      data has sometimes been questioned. The absence of a so-called objective measure
      of sexual behaviour complicates this. Social desirability bias (SDB) is a key
      factor affecting the accuracy of self-reports. Individual, semi-structured
      interviews focusing on possible causes of and solutions to SDB were conducted
      with 30 Batswana women such as those who might enrol in planned vaginal
      microbicide trials. Respondents pointed to shame and the fear of public talk
      about them as key factors contributing to inaccurate self-reports, and they
      stressed the importance of privacy and confidentiality. Interviewer
      characteristics such as age, gender and personality were often viewed as likely
      to affect their candour. Alternative interviewing techniques such as audio
      computer-assisted self-interviewing (ACASI) were appealing to some for the
      potential to reduce embarrassment; others were sceptical. The possible
      implications for HIV-prevention research are presented. 

PMID- 25875237
TI  - Knowing but not knowing: providing maternity care in the context of HIV/AIDS in
      rural Zimbabwe.
AB  - Individual interviews with 25 nurses and midwives revealed their experiences with
      providing maternity care in rural Zimbabwe. These first-hand accounts especially
      illuminate the complexities of providing maternity care in the context of
      HIV/AIDS. The caregivers described feeling troubled by knowing statistics about
      the magnitude and high prevalence of HIV (from official sources and the media)
      while they witnessed the increase in disease and the deaths of women, children
      and colleagues around them. They expressed frustration with a lack of information
      regarding the HIV status of their female patients - a situation exacerbated by
      HIV stigma and poor healthcare organisation. The social relationships between the
      caregivers and women in the study area sometimes meant that the caregivers did
      not effectively apply universal precautions, such as use of gloves during births.
      The situation described by the caregivers emphasises that contextual factors must
      be addressed to meet the increased demands and challenges of providing maternal
      healthcare in endemic HIV/AIDS countries such as Zimbabwe. 

PMID- 25875238
TI  - Preliminary investigation of adherence to antiretroviral therapy among children
      in Aminu Kano Teaching Hospital, Nigeria.
AB  - Treatment of HIV with highly active antiretroviral therapy (HAART) has resulted
      in declining morbidity and mortality rates from HIV-associated diseases, but
      concerns regarding access and adherence are growing. To determine the adherence
      level and the reasons for non-adhering to antiretroviral therapy (ART) among
      children attending the clinic for infectious diseases at Aminu Kano Teaching
      Hospital in Nigeria, a cross-sectional study using the selfreport tool was
      carried out among 40 children with HIV infection who had been on ART for at least
      six months. Thirty-two patients (80%) were 95% or more adherent to their
      medications. The most common reasons for nonadherence were running out of
      medicines and the inability to purchase more due to financial constraints; other
      barriers were non-availability and inaccessibility to medications. Eighty-five
      percent of the paediatric patients took their medications at the same time
      everyday, and scheduled appointments were kept by 87.5%. The social class of the
      patients did not significantly affect adherence level. The level of adherence to
      ART was comparable to levels reported from other developing and developed
      countries. The cost of ART, and availability and accessibility to medications
      were the most significant barriers to adherence. Expanded access to subsidised
      antiretroviral drugs should improve adherence - and consequently treatment
      outcomes - for patients receiving this treatment in resource-poor settings. 

PMID- 25875239
TI  - Sexual discourse and decision-making by urban youth in AIDS-afflicted Swaziland.
AB  - This article begins by considering the ethics and practicalities of researching
      sensitive issues with older children and young adults in the context of HIV/AIDS.
      As part of qualitative fieldwork in the municipality of Mbabane, Swaziland,
      family caregivers and learners at two secondary schools explained how and where
      sexual health knowledge is gained and what they consider to be the main
      influences on sexual decision-making. The findings show that despite one of the
      highest rates of HIV infection in the world, the information reaching youth in
      Swaziland is still often inaccurate and confusing. Young people wanted to be able
      to discuss sexual health issues with informed adults close to them in age and in
      a variety of settings. Peer pressure was an important influence on behaviour and
      led to high-risk behaviour for both genders. Alcohol and cannabis were readily
      available and often linked to high-risk behaviour. Low family incomes and the
      perceived need for luxury goods encouraged female learners to have transactional
      sex with older men. Cultural perceptions of the role of both genders militated
      against low-risk behaviour and left some adolescents feeling marginalised and
      lonely. Ways of approaching these issues at the community level are suggested. 

PMID- 25875240
TI  - Wits University's response to HIV/AIDS: flagship programme or 'tramp steamer'?
AB  - HIV/AIDS is a threat to the creation of human capital and development prospects
      in southern Africa and South Africa. The University of the Witwatersrand (Wits)
      is a well-regarded institution of higher education in Johannesburg. This paper
      outlines the university's qualified failure to implement its HIV/AIDS Policy
      through a comprehensive set of programmes. However, as we describe the
      decommissioning of this potential flagship programme to a 'tramp steamer,' we
      identify a number of challenges to the policy's implementation: the necessary
      scope of an effective programme, the limits to existing capacity, and the need to
      secure funding. We suggest that the key to failure of HIV/AIDS programmes at Wits
      lies with the configurations of power within the university and the funding logic
      that militates against institutions of higher education assuming the high cost of
      HIV/AIDS programmes. Such institutions receive funding and fees irrespective of
      whether or not students complete their education as HIV-positive or negative, are
      aware of their HIV status or not, and - if HIV-positive - are enrolled in a
      disease management programme or not. This financial logic, in which universities
      bear the cost of student HIV/AIDS programmes but receive little short-term
      benefit, poses a threat to the region's future human capital. While institutions
      of higher education may well recognise the moral imperative of responding to
      HIV/AIDS for the benefit of society, current funding models do not support this.
      Four suggestions are put forward to address this unfortunate political economy
      configuration; they involve changing funding formulas, securing direct funding
      from business as the primary recipient of the human capital created, soliciting
      international donor funding, and direct ring-fenced funding offered by
      government. 

PMID- 25875241
TI  - Civil society organisations and the national HIV/AIDS response in Botswana.
AB  - This paper provides preliminary empirical evidence regarding the perceived role
      and actual experiences of HIV/AIDS intervention-focused civil society
      organisations (CSOs) in Botswana's national response. Key informants see the
      national response as government-centred and the role of CSOs within interventions
      as negligible. Despite secondary evidence that indicates a fairly robust and
      diverse civil society community, interviews with CSO personnel revealed that the
      roles and experiences of grassroots organisations are currently hampered by
      spatial, institutional and socio-cultural dynamics of intervention
      operationalisation. This raises questions about the extent to which this scenario
      may create or exacerbate obstacles regarding the efficiency and effectiveness of
      the national HIV/AIDS response in Botswana. 

PMID- 25875242
TI  - Workplace ART programmes: Why do companies invest in them and are they working?
AB  - Prevalence data indicates that certain sectors within the private sector are
      particularly affected by HIV/AIDS. Companies in southern Africa began
      implementing treatment programmes in early 2002 as the corporate sector came to
      realise the financial imperative of offsetting employee morbidity and mortality.
      This article sets about to explain the rationale behind antiretroviral treatment
      (ART) programmes within the private sector while uncovering some of the obstacles
      businesses face when treating HIV-infected employees. Data suggest that in many
      cases employees' uptake of voluntary counselling and testing (VCT) and ART are
      slow. At this early stage of workplace treatment provision, data indicate that
      employers must seek ways to increase uptake of VCT and treatment in an attempt to
      make programmes more cost-effective. 

PMID- 25875243
TI  - Youth have a new attitude on AIDS, but are they talking about it?
AB  - In advocating HIV prevention, organisations such as loveLife in South Africa have
      increasingly used the media to encourage communication and influence behaviour
      change in youth. Our study examined youths' understanding and communication
      habits surrounding loveLife's extensive 'Get Attitude' print campaign. Intrigued
      by the ambiguous campaign message, we implemented a questionnaire-based study in
      three urban KwaZulu-Natal schools to investigate how youth are interpreting the
      images and to determine whether they would connect the personality-aimed message
      with HIV prevention. As communication is a focal point of loveLife's strategy, we
      looked at whether the campaign was successful in fostering discussion and
      examined what factors contributed to or impeded dialogue. One-hundred-and-eighty
      seven Grade 11 students completed the questionnaire, responding to both multiple
      choice and free-response questions about the 'Get Attitude' campaign images. Our
      study was largely exploratory, with the data revealing that the youth did
      interpret the images as intended by loveLife. While the campaign failed to
      stimulate discussion for many of the youth, those who did talk about the campaign
      were more likely to speak to their teachers than to parents or friends. 

PMID- 25875244
TI  - Intrapartum practices to limit vertical transmission of HIV.
AB  - The need to improve health services to HIV-positive women requires a specific
      focus on limiting mother-to-child transmission. Vertical transmission most often
      takes place during the intrapartum period; hence, it is essential to alert
      midwives to what constitutes safe or risky intrapartum practices. Midwives in the
      southern region of the North West Province of South Africa were surveyed for
      their knowledge of safe intrapartum practices that can limit vertical
      transmission of HIV, consequently indicating which intrapartum practices prevail
      in the region. We used a quantitative survey design and collected data by means
      of a questionnaire and checklist. A purposeful availability sample of 31 midwives
      who work in all four hospitals in the province was used and a random sample of
      401 obstetric records was audited. Data were analysed by means of frequency
      analysis, effect sizes and cross-reference. A slight majority of the midwives had
      sufficient knowledge to distinguish between risky and safe practices. However,
      safe intrapartum practices are not always carried out and this raises concerns.
      Accordingly, we formulate general recommendations for nursing education, future
      research, and midwifery practice. In particular we suggest ways the national
      Guidelines for Maternity Care in South Africa may be adapted and better
      implemented to enhance safe intrapartum practices to limit vertical transmission
      of HIV. 

PMID- 25875245
TI  - MAPK signaling pathway alters expression of midgut ALP and ABCC genes and causes
      resistance to Bacillus thuringiensis Cry1Ac toxin in diamondback moth.
AB  - Insecticidal crystal toxins derived from the soil bacterium Bacillus
      thuringiensis (Bt) are widely used as biopesticide sprays or expressed in
      transgenic crops to control insect pests. However, large-scale use of Bt has led
      to field-evolved resistance in several lepidopteran pests. Resistance to Bt
      Cry1Ac toxin in the diamondback moth, Plutella xylostella (L.), was previously
      mapped to a multigenic resistance locus (BtR-1). Here, we assembled the 3.15 Mb
      BtR-1 locus and found high-level resistance to Cry1Ac and Bt biopesticide in four
      independent P. xylostella strains were all associated with differential
      expression of a midgut membrane-bound alkaline phosphatase (ALP) outside this
      locus and a suite of ATP-binding cassette transporter subfamily C (ABCC) genes
      inside this locus. The interplay between these resistance genes is controlled by
      a previously uncharacterized trans-regulatory mechanism via the mitogen-activated
      protein kinase (MAPK) signaling pathway. Molecular, biochemical, and functional
      analyses have established ALP as a functional Cry1Ac receptor. Phenotypic
      association experiments revealed that the recessive Cry1Ac resistance was tightly
      linked to down-regulation of ALP, ABCC2 and ABCC3, whereas it was not linked to
      up-regulation of ABCC1. Silencing of ABCC2 and ABCC3 in susceptible larvae
      reduced their susceptibility to Cry1Ac but did not affect the expression of ALP,
      whereas suppression of MAP4K4, a constitutively transcriptionally-activated MAPK
      upstream gene within the BtR-1 locus, led to a transient recovery of gene
      expression thereby restoring the susceptibility in resistant larvae. These
      results highlight a crucial role for ALP and ABCC genes in field-evolved
      resistance to Cry1Ac and reveal a novel trans-regulatory signaling mechanism
      responsible for modulating the expression of these pivotal genes in P.
      xylostella. 

PMID- 25875246
TI  - A tetravalent bispecific TandAb (CD19/CD3), AFM11, efficiently recruits T cells
      for the potent lysis of CD19(+) tumor cells.
AB  - To harness the potent tumor-killing capacity of T cells for the treatment of
      CD19(+) malignancies, we constructed AFM11, a humanized tetravalent bispecific
      CD19/CD3 tandem diabody (TandAb) consisting solely of Fv domains. The molecule
      exhibits good manufacturability and stability properties. AFM11 has 2 binding
      sites for CD3 and 2 for CD19, an antigen that is expressed from early B cell
      development through differentiation into plasma cells, and is an attractive
      alternative to CD20 as a target for the development of therapeutic antibodies to
      treat B cell malignancies. Comparison of the binding and cytotoxicity of AFM11
      with those of a tandem scFv bispecific T cell engager (BiTE) molecule targeting
      the same antigens revealed that AFM11 elicited more potent in vitro B cell lysis.
      Though possessing high affinity to CD3, the TandAb mediates serial-killing of
      CD19(+) cells with little dependence of potency or efficacy upon effector:target
      ratio, unlike the BiTE. The advantage of the TandAb over the BiTE was most
      pronounced at lower effector:target ratios. AFM11 mediated strictly target
      dependent T cell activation evidenced by CD25 and CD69 induction, proliferation,
      and cytokine release, notwithstanding bivalent CD3 engagement. In a NOD/scid
      xenograft model, AFM11 induced dose-dependent growth inhibition of Raji tumors in
      vivo, and radiolabeled TandAb exhibited excellent localization to tumor but not
      to normal tissue. After intravenous administration in mice, half-life ranged from
      18.4 to 22.9 h. In a human ex vivo B-cell chronic lymphocytic leukemia study,
      AFM11 exhibited substantial cytotoxic activity in an autologous setting. Thus,
      AFM11 may represent a promising therapeutic for treatment of CD19(+) malignancies
      with an advantageous safety risk profile and anticipated dosing regimen.

PMID- 25875247
TI  - Identification of common regulators of genes in co-expression networks affecting
      muscle and meat properties.
AB  - Understanding the genetic contributions behind skeletal muscle composition and
      metabolism is of great interest in medicine and agriculture. Attempts to dissect
      these complex traits combine genome-wide genotyping, expression data analyses and
      network analyses. Weighted gene co-expression network analysis (WGCNA) groups
      genes into modules based on patterns of co-expression, which can be linked to
      phenotypes by correlation analysis of trait values and the module eigengenes,
      i.e. the first principal component of a given module. Network hub genes and
      regulators of the genes in the modules are likely to play an important role in
      the emergence of respective traits. In order to detect common regulators of genes
      in modules showing association with meat quality traits, we identified eQTL for
      each of these genes, including the highly connected hub genes. Additionally, the
      module eigengene values were used for association analyses in order to derive a
      joint eQTL for the respective module. Thereby major sites of orchestrated
      regulation of genes within trait-associated modules were detected as hotspots of
      eQTL of many genes of a module and of its eigengene. These sites harbor likely
      common regulators of genes in the modules. We exemplarily showed the consistent
      impact of candidate common regulators on the expression of members of respective
      modules by RNAi knockdown experiments. In fact, Cxcr7 was identified and
      validated as a regulator of genes in a module, which is involved in the function
      of defense response in muscle cells. Zfp36l2 was confirmed as a regulator of
      genes of a module related to cell death or apoptosis pathways. The integration of
      eQTL in module networks enabled to interpret the differentially-regulated genes
      from a systems perspective. By integrating genome-wide genomic and transcriptomic
      data, employing co-expression and eQTL analyses, the study revealed likely
      regulators that are involved in the fine-tuning and synchronization of genes with
      trait-associated expression. 

PMID- 25875248
TI  - Trace elements and radionuclides in palm oil, soil, water, and leaves from oil
      palm plantations: A review.
AB  - Oil palm (Elaeisguineensis) is one of the most productive oil producing plant in
      the world. Crude palm oil is composed of triglycerides supplying the world's need
      of edible oils and fats. Palm oil also provides essential elements and
      antioxidants that are potential mediators of cellular functions. Experimental
      studies have demonstrated the toxicity of the accumulation of significant amounts
      of nonessential trace elements and radionuclides in palm oil that affects the
      health of consumers. It has been reported that uptake of trace elements and
      radionuclides from the oil palm tree may be from water and soil on the palm
      plantations. In the present review, an attempt was made to revise and access
      knowledge on the presence of some selected trace elements and radionuclides in
      palm oil, soil, water, and leaves from oil palm plantations based on the
      available facts and data. Existing reports show that the presence of nonessential
      trace elements and radionuclides in palm oil may be from natural or anthropogenic
      sources in the environment. However, the available literature is limited and
      further research need to be channeled to the investigation of trace elements and
      radionuclides in soil, water, leaves, and palm oil from oil palm plantations
      around the globe.

PMID- 25875249
TI  - Overview of 15-year severe combined immunodeficiency in the Netherlands: towards
      newborn blood spot screening.
AB  - Severe combined immune deficiency (SCID) is a fatal primary immunodeficiency
      usually presenting in the first months of life with (opportunistic) infections,
      diarrhea, and failure to thrive. Hematopoietic stem cell transplantation (HSCT)
      and gene therapy (GT) are curative treatment options. The objective of the study
      was to assess the morbidity, mortality, and diagnostic and therapeutic delay in
      children with SCID in the Netherlands in the last 15 years. These data may help
      to judge whether SCID should be considered to be included in our national
      neonatal screening program. In the period 1998-2013, 43 SCID patients were
      diagnosed in the Netherlands, 11 of whom were atypical SCID (presentation beyond
      the first year). The median interval between the first symptom and diagnosis was
      2 months (range 0-1173 months). The total mortality was 42 %. In total, 32
      patients were treated with HSCT of whom 8 were deceased. Nine patients died due
      to severe infectious complications before curative treatment could be initiated.
      CONCLUSION: Because of a high mortality of patients with SCID before HSCT could
      be initiated, only a national newborn screening program and pre-emptive HSCT or
      GT will be able to improve survival of these patients. "WHAT IS KNOWN": * SCID is
      a fatal disease if a curative hematopoietic stem cell transplantation cannot be
      performed in time. * Newborn screening for SCID enables early diagnosis in the
      asymptomatic phase. "WHAT IS NEW": * Nine out of 43 SCID patients in the
      Netherlands died due to severe infectious complications before curative treatment
      could be initiated. * Only newborn screening and pre-emptive curative therapy
      will improve survival of children with SCID in the Netherlands.

PMID- 25875250
TI  - Performance of PRISM III and PELOD-2 scores in a pediatric intensive care unit.
AB  - The study aims were to compare two models (The Pediatric Risk of Mortality III
      (PRISM III) and Pediatric Logistic Organ Dysfunction (PELOD-2)) for prediction of
      mortality in a pediatric intensive care unit (PICU) and recalibrate PELOD-2 in a
      Portuguese population. To achieve the previous goal, a prospective cohort study
      to evaluate score performance (standardized mortality ratio, discrimination, and
      calibration) for both models was performed. A total of 556 patients consecutively
      admitted to our PICU between January 2011 and December 2012 were included in the
      analysis. The median age was 65 months, with an interquartile range of 1 month to
      17 years. The male-to-female ratio was 1.5. The median length of PICU stay was 3
      days. The overall predicted number of deaths using PRISM III score was 30.8
      patients whereas that by PELOD-2 was 22.1 patients. The observed mortality was 29
      patients. The area under the receiver operating characteristics curve for the two
      models was 0.92 and 0.94, respectively. The Hosmer and Lemeshow goodness-of-fit
      test showed a good calibration only for PRISM III (PRISM III: chi (2) = 3.820, p
      = 0.282; PELOD-2: chi (2) = 9.576, p = 0.022). CONCLUSIONS: Both scores had good
      discrimination. PELOD-2 needs recalibration to be a better reliable prediction
      tool. WHAT IS KNOWN: * PRISM III (Pediatric Risk of Mortality III) and PELOD
      (Pediatric Logistic Organ Dysfunction) scores are frequently used to assess the
      performance of intensive care units and also for mortality prediction in the
      pediatric population. * Pediatric Logistic Organ Dysfunction 2 is the newer
      version of PELOD and has recently been validated with good discrimination and
      calibration. What is New: * In our population, both scores had good
      discrimination. * PELOD-2 needs recalibration to be a better reliable prediction
      tool.

PMID- 25875251
TI  - Acute pulmonary edema following liposuction due to heart failure and atypical
      pneumonia.
AB  - Microcannular liposuction in tumescent anesthesia is the most effective treatment
      for painful lipedema. Tumescent anesthesia is an established and safe procedure
      in local analgesia when performed according to guidelines. Major adverse effects
      are rare. In patients with advanced lipedema, however, the commonly presented
      comorbidities bear additional risks.We report on post-surgical acute pulmonary
      edema after tumescent liposuction according to guidelines in a 52-year-old female
      patient with lipedema of the legs. We discuss in detail possible scenarios that
      might be involved in such emergency. In the present case the most likely was a
      retarded community acquired atypical pneumonia with aggravation of pre-existent
      comorbidities.A combined treatment with intravenous b-lactam antibiosis, positive
      pressure ventilation, and continuous venovenous hemodialysis and filtration
      resulted in complete remission in a couple of days. In conclusion, tumescent
      liposuction of advanced lipedema patients should only be performed in well
      trained centers with sufficient infrastructure.

PMID- 25875252
TI  - The quality of clinical maternal and neonatal healthcare - a strategy for
      identifying 'routine care signal functions'.
AB  - BACKGROUND: A variety of clinical process indicators exists to measure the
      quality of care provided by maternal and neonatal health (MNH) programs. To allow
      comparison across MNH programs in low- and middle-income countries (LMICs), a
      core set of essential process indicators is needed. Although such a core set is
      available for emergency obstetric care (EmOC), the 'EmOC signal functions', a
      similar approach is currently missing for MNH routine care evaluation. We
      describe a strategy for identifying core process indicators for routine care and
      illustrate their usefulness in a field example. METHODS: We first developed an
      indicator selection strategy by combining epidemiological and programmatic
      aspects relevant to MNH in LMICs. We then identified routine care process
      indicators meeting our selection criteria by reviewing existing quality of care
      assessment protocols. We grouped these indicators into three categories based on
      their main function in addressing risk factors of maternal or neonatal
      complications. We then tested this indicator set in a study assessing MNH quality
      of clinical care in 33 health facilities in Malawi. RESULTS: Our strategy
      identified 51 routine care processes: 23 related to initial patient risk
      assessment, 17 to risk monitoring, 11 to risk prevention. During the clinical
      performance assessment a total of 82 cases were observed. Birth attendants'
      adherence to clinical standards was lowest in relation to risk monitoring
      processes. In relation to major complications, routine care processes addressing
      fetal and newborn distress were performed relatively consistently, but there were
      major gaps in the performance of routine care processes addressing bleeding,
      infection, and pre-eclampsia risks. CONCLUSION: The identified set of process
      indicators could identify major gaps in the quality of obstetric and neonatal
      care provided during the intra- and immediate postpartum period. We hope our
      suggested indicators for essential routine care processes will contribute to
      streamlining MNH program evaluations in LMICs.

PMID- 25875254
TI  - Tuberculosis among the homeless--preventing another outbreak through community
      action.

PMID- 25875255
TI  - The National Children's Study--end or new beginning?

PMID- 25875253
TI  - Dual roles of palladin protein in in vitro myogenesis: inhibition of early
      induction but promotion of myotube maturation.
AB  - Palladin is a microfilament-associated phosphoprotein whose function in skeletal
      muscle has rarely been studied. Therefore, we investigate whether myogenesis is
      influenced by the depletion of palladin expression known to interfere with the
      actin cytoskeleton dynamic required for skeletal muscle differentiation. The
      inhibition of palladin in C2C12 myoblasts leads to precocious myogenic
      differentiation with a concomitant reduction in cell apoptosis. This premature
      myogenesis is caused, in part, by an accelerated induction of p21, myogenin, and
      myosin heavy chain, suggesting that palladin acts as a negative regulator in
      early differentiation phases. Paradoxically, palladin-knockdown myoblasts are
      unable to differentiate terminally, despite their ability to perform some initial
      steps of differentiation. Cells with attenuated palladin expression form thinner
      myotubes with fewer myonuclei compared to those of the control. It is noteworthy
      that a negative regulator of myogenesis, myostatin, is activated in palladin
      deficient myotubes, suggesting the palladin-mediated impairment of late-stage
      myogenesis. Additionally, overexpression of 140-kDa palladin inhibits myoblast
      differentiation while 200-kDa and 90-kDa palladin-overexpressed cells display an
      enhanced differentiation rate. Together, our data suggest that palladin might
      have both positive and negative roles in maintaining the proper skeletal myogenic
      differentiation in vitro. 

PMID- 25875256
TI  - Apremilast for Behcet's syndrome--a phase 2, placebo-controlled study.
AB  - BACKGROUND: Oral ulcers, the hallmark of Behcet's syndrome, can be resistant to
      conventional treatment; therefore, alternative agents are needed. Apremilast is
      an oral phosphodiesterase-4 inhibitor that modulates several inflammatory
      pathways. METHODS: We conducted a phase 2, multicenter, placebo-controlled study
      in which 111 patients with Behcet's syndrome who had two or more oral ulcers were
      randomly assigned to receive 30 mg of apremilast twice daily or placebo for 12
      weeks. This regimen was followed by a 12-week extension phase in which the
      placebo group was switched to apremilast and a 28-day post-treatment
      observational follow-up phase. The patients and clinicians were unaware of the
      study assignments throughout the trial. The primary end point was the number of
      oral ulcers at week 12. Secondary outcomes included pain from these ulcers
      (measured on a 100-mm visual-analogue scale, with higher scores indicating worse
      pain), the number of genital ulcers, overall disease activity, and quality of
      life. RESULTS: The mean (+/-SD) number of oral ulcers per patient at week 12 was
      significantly lower in the apremilast group than in the placebo group (0.5+/-1.0
      vs. 2.1+/-2.6) (P<0.001). The mean decline in pain from oral ulcers from baseline
      to week 12 was greater with apremilast than with placebo (-44.7+/-24.3 mm vs. 
      16.0+/-32.5 mm) (P<0.001). Nausea, vomiting, and diarrhea were more common in the
      apremilast group (with 22, 9, and 12 incidents, respectively, among 55 patients)
      than in the placebo group (with 10, 1, and 2 incidents, respectively, among 56
      patients), findings that were similar to those in previous studies of apremilast.
      There were two serious adverse events in patients receiving apremilast.
      CONCLUSIONS: Apremilast was effective in treating oral ulcers, which are the
      cardinal manifestation of Behcet's syndrome. This preliminary study was neither
      large enough nor long enough to assess long-term efficacy, the effect on other
      manifestations of Behcet's syndrome, or the risk of uncommon serious adverse
      events. (Funded by Celgene; ClinicalTrials.gov number, NCT00866359.).

PMID- 25875257
TI  - A randomized, controlled trial of an aerosolized vaccine against measles.
AB  - BACKGROUND: Aerosolized vaccine can be used as a needle-free method of
      immunization against measles, a disease that remains a major cause of illness and
      death. Data on the immunogenicity of aerosolized vaccine against measles in
      children are inconsistent. METHODS: We conducted an open-label noninferiority
      trial involving children 9.0 to 11.9 months of age in India who were eligible to
      receive a first dose of measles vaccine. Children were randomly assigned to
      receive a single dose of vaccine by means of either aerosol inhalation or a
      subcutaneous injection. The primary end points were seropositivity for antibodies
      against measles and adverse events 91 days after vaccination. The noninferiority
      margin was 5 percentage points. RESULTS: A total of 1001 children were assigned
      to receive aerosolized vaccine, and 1003 children were assigned to receive
      subcutaneous vaccine; 1956 of all the children (97.6%) were followed to day 91,
      but outcome data were missing for 331 children because of thawed specimens. In
      the per-protocol population, data on 1560 of 2004 children (77.8%) could be
      evaluated. At day 91, a total of 662 of 775 children (85.4%; 95% confidence
      interval [CI], 82.5 to 88.0) in the aerosol group, as compared with 743 of 785
      children (94.6%; 95% CI, 92.7 to 96.1) in the subcutaneous group, were
      seropositive, a difference of -9.2 percentage points (95% CI, -12.2 to -6.3).
      Findings were similar in the full-analysis set (673 of 788 children in the
      aerosol group [85.4%] and 754 of 796 children in the subcutaneous group [94.7%]
      were seropositive at day 91, a difference of -9.3 percentage points [95% CI, 
      12.3 to -6.4]) and after multiple imputation of missing results. No serious
      adverse events were attributable to measles vaccination. Adverse-event profiles
      were similar in the two groups. CONCLUSIONS: Aerosolized vaccine against measles
      was immunogenic, but, at the prespecified margin, the aerosolized vaccine was
      inferior to the subcutaneous vaccine with respect to the rate of seropositivity.
      (Funded by the Bill and Melinda Gates Foundation; Measles Aerosol Vaccine Project
      Clinical Trials Registry-India number, CTRI/2009/091/000673.).

PMID- 25875259
TI  - Clostridium difficile infection.

PMID- 25875258
TI  - Preoperative medical testing in Medicare patients undergoing cataract surgery.
AB  - BACKGROUND: Routine preoperative testing is not recommended for patients
      undergoing cataract surgery, because testing neither decreases adverse events nor
      improves outcomes. We sought to assess adherence to this guideline, estimate
      expenditures from potentially unnecessary testing, and identify patient and
      health care system characteristics associated with potentially unnecessary
      testing. METHODS: Using an observational cohort of Medicare beneficiaries
      undergoing cataract surgery in 2011, we determined the prevalence and cost of
      preoperative testing in the month before surgery. We compared the prevalence of
      preoperative testing and office visits with the mean percentage of beneficiaries
      who underwent tests and had office visits during the preceding 11 months. Using
      multivariate hierarchical analyses, we examined the relationship between
      preoperative testing and characteristics of patients, health system
      characteristics, surgical setting, care team, and occurrence of a preoperative
      office visit. RESULTS: Of 440,857 patients, 53% had at least one preoperative
      test in the month before surgery. Expenditures on testing during that month were
      $4.8 million higher and expenditures on office visits $12.4 million higher (42%
      and 78% higher, respectively) than the mean monthly expenditures during the
      preceding 11 months. Testing varied widely among ophthalmologists; 36% of
      ophthalmologists ordered preoperative tests for more than 75% of their patients.
      A patient's probability of undergoing testing was associated mainly with the
      ophthalmologist who managed the preoperative evaluation. CONCLUSIONS:
      Preoperative testing before cataract surgery occurred frequently and was more
      strongly associated with provider practice patterns than with patient
      characteristics. (Funded by the Foundation for Anesthesia Education and Research
      and the Grove Foundation.).

PMID- 25875260
TI  - Images in clinical medicine. Hyphema.

PMID- 25875261
TI  - Case records of the Massachusetts General Hospital. Case 12-2015. A newborn boy
      with respiratory distress, lethargy, and hypernatremia.

PMID- 25875262
TI  - Toward a true bacteriotherapy for Clostridium difficile infection.

PMID- 25875263
TI  - New agents for hyperkalemia.

PMID- 25875264
TI  - New agents for hyperkalemia.

PMID- 25875265
TI  - New agents for hyperkalemia.

PMID- 25875266
TI  - New agents for hyperkalemia.

PMID- 25875267
TI  - New agents for hyperkalemia.

PMID- 25875268
TI  - Trends in opioid analgesic abuse and mortality in the United States.

PMID- 25875269
TI  - Trends in opioid analgesic abuse and mortality in the United States.

PMID- 25875270
TI  - Trends in opioid analgesic abuse and mortality in the United States.

PMID- 25875271
TI  - Origins of cystic fibrosis lung disease.

PMID- 25875272
TI  - Origins of cystic fibrosis lung disease.

PMID- 25875273
TI  - More on hidden formaldehyde in e-cigarette aerosols.

PMID- 25875274
TI  - More on hidden formaldehyde in e-cigarette aerosols.

PMID- 25875275
TI  - More on hidden formaldehyde in e-cigarette aerosols.

PMID- 25875276
TI  - More on hidden formaldehyde in e-cigarette aerosols.

PMID- 25875277
TI  - Sodium zirconium cyclosilicate for urgent therapy of severe hyperkalemia.

PMID- 25875278
TI  - Images in clinical medicine. Loss of fingerprints.

PMID- 25875279
TI  - Correction: comparison of multiple displacement amplification (MDA) and multiple
      annealing and looping-based amplification cycles (MALBAC) in single-cell
      sequencing.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0114520.]. 

PMID- 25875280
TI  - Isolation and properties of cellulose nanofibrils from coconut palm petioles by
      different mechanical process.
AB  - In this study, cellulose nanofibrils (CNFs) were successfully isolated from
      coconut palm petiole residues falling off naturally with chemical pretreatments
      and mechanical treatments by a grinder and a homogenizor. FTIR spectra analysis
      showed that most of hemicellulose and lignin were removed from the fiber after
      chemical pretreatments. The compositions of CNFS indicated that high purity of
      nanofibrils with cellulose contain more than 95% was obtained. X-ray
      diffractogram demonstrated that chemical pretreatments significantly increased
      the crystallinity of CNFs from 38.00% to 70.36%; however, 10-15 times of grinding
      operation followed by homogenizing treatment after the chemical pretreatments did
      not significantly improve the crystallinity of CNFs. On the contrary, further
      grinding operation could destroy crystalline regions of the cellulose. SEM image
      indicated that high quality of CNFs could be isolated from coconut palm petiole
      residues with chemical treatments in combination of 15 times of grinding followed
      by 10 times of homogenization and the aspect ratio of the obtained CNFs ranged
      from 320 to 640. The result of TGA-DTG revealed that the chemical-mechanical
      treatments improved thermal stability of fiber samples, and the CNFs with 15
      grinding passing times had the best thermal stability. This work suggests that
      the CNFs can be successfully extracted from coconut palm petiole residues and it
      may be a potential feedstock for nanofiber reinforced composites due to its high
      aspect ratio and crystallinity. 

PMID- 25875281
TI  - Incomplete assessments: towards a better understanding of causes and solutions.
      The case of the interRAI home care instrument in Belgium.
AB  - The chronic diseases, comorbidities and rapidly changing needs of frail older
      persons increase the complexity of caregiving. A comprehensive, systematic and
      structured collection of data on the status of the frail older person is presumed
      to be essential in facilitating decision-making and thus improving the quality of
      care provided. However, the way in which an assessment is completed has a
      substantial impact on the quality and value of the results. This study examines
      the online completion of interRAI Home Care assessments, the possible causes for
      incomplete assessments and the consequences of these factors with respect to the
      quality of care received. Our findings indicate high nurse engagement and poor
      physician participation. We also observed the poor completion of items in
      predominantly medically- oriented sections characterized by, first, the fact that
      the assessors felt incapable of answering certain questions, second, the absence
      of required data or of a competent person to fill out the data, and third, the
      lack of tools necessary for essential measurements. The incompleteness of
      assessments has a clear negative influence on outcome generation. Moreover,
      without the added value of support outcomes, the improvement of care quality can
      be impeded and information technology can easily be seen as burdensome by the
      assessors. We have observed that multidisciplinary cooperation is an important
      prerequisite to establishing high-quality assessments aimed at improving the
      quality of care. 

PMID- 25875282
TI  - Attenuation of progressive hearing loss in DBA/2J mice by reagents that affect
      epigenetic modifications is associated with up-regulation of the zinc importer
      Zip4.
AB  - Various factors that are important for proper hearing have been identified,
      including serum levels of zinc. Here we investigated whether epigenetic
      regulatory pathways, which can be modified by environmental factors, could
      modulate hearing. RT-PCR detected expression of genes encoding DNA
      methyltransferase and histone deacetylase (Hdac) in the postnatal as well as
      adult mouse auditory epithelium. DBA/2J mice, which are a model for progressive
      hearing loss, were injected subcutaneously with one or a combination of the
      following reagents: <smallcaps>L</smallcaps>-methionine as a methyl donor,
      valproic acid as a pan-Hdac inhibitor, and folic acid and vitamin B12 as putative
      factors involved in age-related hearing loss. The mice were treated from ages 4
      to 12 weeks (N >= 5), and auditory brainstem response (ABR) thresholds were
      measured at 8, 16, and 32 kHz. Treatment of the mice with a combination of
      <smallcaps>L</smallcaps>-methionine and valproic acid (M+V) significantly reduced
      the increase in the ABR threshold at 32 kHz. Treatment with any of these reagents
      individually produced no such effect. Microarray analyses detected 299 gene
      probes that were significantly up- or down-regulated in the cochleae of mice
      treated with M+V compared with the control vehicle-treated mice. Quantitative RT
      PCR confirmed significant up-regulation of a zinc importer gene, Zip4, in the
      cochleae of mice treated with M+V. Immunohistochemistry demonstrated an intense
      Zip4 signal in cochlear tissues such as the lateral wall, organ of Corti, and
      spiral ganglion. Finally, mice treated with the Zip4 inducer (-)-epigallocatechin
      3-O-gallate showed a significant reduction in the increase of the ABR threshold
      at 32 kHz and up-regulation of Zip4 expression in the cochlea. This study
      suggests that epigenetic regulatory pathways can modify auditory function and
      that zinc intake in the cochlea via Zip4 mediates maintenance of mammalian
      hearing. 

PMID- 25875283
TI  - Cognitive demands of lower paleolithic toolmaking.
AB  - Stone tools provide some of the most abundant, continuous, and high resolution
      evidence of behavioral change over human evolution, but their implications for
      cognitive evolution have remained unclear. We investigated the neurophysiological
      demands of stone toolmaking by training modern subjects in known Paleolithic
      methods ("Oldowan", "Acheulean") and collecting structural and functional brain
      imaging data as they made technical judgments (outcome prediction, strategic
      appropriateness) about planned actions on partially completed tools. Results show
      that this task affected neural activity and functional connectivity in dorsal
      prefrontal cortex, that effect magnitude correlated with the frequency of correct
      strategic judgments, and that the frequency of correct strategic judgments was
      predictive of success in Acheulean, but not Oldowan, toolmaking. This
      corroborates hypothesized cognitive control demands of Acheulean toolmaking,
      specifically including information monitoring and manipulation functions
      attributed to the "central executive" of working memory. More broadly, it
      develops empirical methods for assessing the differential cognitive demands of
      Paleolithic technologies, and expands the scope of evolutionary hypotheses that
      can be tested using the available archaeological record. 

PMID- 25875284
TI  - Altered cortical activation during action observation in amyotrophic lateral
      sclerosis patients: a parametric functional MRI study.
AB  - OBJECTIVES: To investigate functional cerebral abnormalities in patients with
      amyotrophic lateral sclerosis (ALS) using functional magnetic resonance imaging
      (fMRI) during action observation. METHODS: Thirty patients with ALS and 30
      matched healthy controls underwent fMRI with an experimental paradigm while
      observing a video of repetitive flexion-extension of the fingers at three
      frequency levels or three complexity levels, alternated with periods of a static
      hand. A parametric analysis was applied to determine the effects of each of the
      two factors. RESULTS: Action observation activated similar neural networks as the
      research on execution of action in the ALS patients and healthy subjects in
      several brain regions related to the mirror-neuron system (MNS). In the ALS
      patients, in particular, the dorsal lateral premotor cortex (dPMC), inferior
      parietal gyrus (IPG), and SMA, were more activated compared with the activation
      in the controls. Increased activation within the primary motor cortex (M1), dPMC,
      inferior frontal gyrus (IFG), and superior parietal gyrus (SPG) mainly correlated
      with hand movement frequency/complexity in the videos in the patients compared
      with controls. CONCLUSIONS: The findings indicated an ongoing compensatory
      process occurring within the higher order motor-processing system of ALS
      patients, likely to overcome the loss of function. KEY POINTS: * Action
      observation activated similar core nodes of MNS in ALS and controls. * Increased
      activation within M1, dPMC, IFG and SPG mainly correlated with hand movement
      frequency/complexity. * Differences in patients and controls may be due to
      compensatory processes in ALS.

PMID- 25875285
TI  - Bone marrow involvement in Gaucher disease at MRI : what long-term evolution can
      we expect under enzyme replacement therapy?
AB  - PURPOSE: To study the long-term evolution of the bone marrow burden (BMB) score
      at MRI in patients with Gaucher disease (GD) under enzyme replacement therapy
      (ERT). MATERIAL AND METHODS: Forty patients treated for GD were retrospectively
      studied in a referral centre. BMB scores were assessed on spine and femur MR
      examinations performed between January 2003 and June 2014. The long-term
      evolution of the BMB scores was analyzed using a linear mixed model. RESULTS: A
      total of 121 MRI examinations were performed during the study period with a mean
      follow-up of 7.1 years +/- 5.6, an average rate of 3.1 MR examinations +/- 1.7
      per patient and an interval of 2.3 years +/- 1.1 between examinations. Patients
      had received ERT during 12 years on average +/- 6.7. The trend of BMB scores with
      time decreased significantly by 15% (P = 0.008) during the total study period and
      39% (P = 0.01) during the first 5 years of treatment. No changes in BMB scores
      were observed after five years of treatment. CONCLUSION: In Gaucher patients, the
      trend of MRI BMB scores with time decreased significantly under ERT the first 5
      years of treatment before a long-term stabilization. KEY POINTS: * Bone marrow
      infiltration of Gaucher patients responds to enzyme replacement therapy * MRI BMB
      score decreases mainly during the first five years of treatment * MRI BMB score
      tends to stabilize after five years of treatment * MR examinations could be
      limited after five years of treatment.

PMID- 25875286
TI  - Increased signal intensity at the proximal patellar tendon: correlation between
      MR imaging and histology in eight cadavers and clinical MR imaging studies.
AB  - OBJECTIVES: We set out to investigate the cause of persistently increased signal
      intensity (SI) in the posterior portion of the proximal patellar tendon (pPT) on
      T1-weighted images (T1WI). METHODS: MR imaging was performed in eight cadavers,
      followed by gross histological examination. In addition, 84 patients without
      trauma history or anterior knee pain were included to compare the SI of the PTs.
      The patients were divided according to their age, sex, and Kellgren-Lawrence (KL)
      grades. The length and thickness of the increased SI portion in the pPT and whole
      PT (wPT) on T1WI were recorded. RESULTS: Histological specimens demonstrated that
      the adipose tissue, vessels, and perivascular connective tissue invaginated into
      the posterior portion of the pPT. This histological anatomy corresponded to the
      pPT signal change on MR imaging. There was linear and interdigitating increased
      SI of the pPT in all of the 84 patients (100%). There were no differences in the
      lengths and thicknesses of the increased SI portion of pPTs and wPTs according to
      age, sex, and KL grade (all p > 0.05). CONCLUSIONS: The increased SI of the pPT
      on T1WI and fluid-sensitive MR images results from invaginating fat, vessels, and
      perivascular connective tissue. It is not pathological, but a normal and common
      finding. KEY POINTS: * Increased linear/interdigitated SIs of the pPT is a normal
      and common finding. * Invaginated adipose tissue, vessels, and connective tissue
      could contribute to increased SI. * The fibrocartilage has a minimal role in
      increased SI of the pPT. * Age, sex, and KL grade do not significantly influence
      the increased SI. * Knowledge of this increased SI should help clinicians to
      avoid unnecessary treatment.

PMID- 25875287
TI  - Automated CT-based segmentation and quantification of total intracranial volume.
AB  - OBJECTIVES: To develop an algorithm to segment and obtain an estimate of total
      intracranial volume (tICV) from computed tomography (CT) images. MATERIALS AND
      METHODS: Thirty-six CT examinations from 18 patients were included. Ten patients
      were examined twice the same day and eight patients twice six months apart (these
      patients also underwent MRI). The algorithm combines morphological operations,
      intensity thresholding and mixture modelling. The method was validated against
      manual delineation and its robustness assessed from repeated imaging
      examinations. Using automated MRI software, the comparability with MRI was
      investigated. Volumes were compared based on average relative volume differences
      and their magnitudes; agreement was shown by a Bland-Altman analysis graph.
      RESULTS: We observed good agreement between our algorithm and manual delineation
      of a trained radiologist: the Pearson's correlation coefficient was r = 0.94,
      tICVml[manual] = 1.05 * tICVml[automated] - 33.78 (R(2) = 0.88). Bland-Altman
      analysis showed a bias of 31 mL and a standard deviation of 30 mL over a range of
      1265 to 1526 mL. CONCLUSIONS: tICV measurements derived from CT using our
      proposed algorithm have shown to be reliable and consistent compared to manual
      delineation. However, it appears difficult to directly compare tICV measures
      between CT and MRI. KEY POINTS: * Automated estimation of tICV is in good
      agreement with manual tracing. * Consistent tICV estimations from repeated
      measurements demonstrate the robustness of the algorithm. * Automatically
      segmented volumes seem less variable than those from manual tracing. * Unbiased
      and automated tlCV estimation is possible from CT.

PMID- 25875289
TI  - Reaction-based turn-on fluorescent probes with magnetic responses for Fe(2+)
      detection in live cells.
AB  - Iron is the most abundant nutritionally essential transition metal found in the
      human body. It plays important roles in various biological processes such as
      oxygen delivery, electron transport, enzymatic reactions and DNA synthesis and
      repair. However, iron can also catalyze the production of free radicals, which
      are linked to quite a few diseases such as cancer, neurodegenerative diseases,
      and cardiovascular diseases. Both iron deficiency and iron overload are related
      to various health problems. Thus, precisely monitoring iron ions (Fe(2+) and
      Fe(3+)) in biological systems is important in understanding the detailed
      biological functions of iron and its trafficking pathways. However, effective
      tools for monitoring labile Fe(2+) in biological systems have not yet been
      established. Reported herein are turn on, reaction-based coumarin and rhodamine
      linked nitroxide probes (Cou-T and Rh-T) for selective detection of Fe(2+) in
      solution and in living cells. Rh-T displayed a unique change in the EPR signal as
      well as enhancement of the fluorescence signal resulting from a specific redox
      reaction between the probe and Fe(2+). The turn-on fluorescence response towards
      Fe(2+) allows the subcellular imaging of endogenous Fe(2+) as well as imaging
      under conditions of external iron supplementation or depletion, with a labile
      Fe(2+) pool located in the mitochondria of human fibroblast primary cells. The
      detection and mechanism were verified by the magnetic properties of the probe via
      electron paramagnetic resonance (EPR) spectroscopy in solution and in cells. 

PMID- 25875288
TI  - Endogenous brain pericytes are widely activated and contribute to mouse glioma
      microvasculature.
AB  - Glioblastoma multiforme (GBM) is the most common brain tumor in adults. It
      presents an extremely challenging clinical problem, and treatment very frequently
      fails due to the infiltrative growth, facilitated by extensive angiogenesis and
      neovascularization. Pericytes constitute an important part of the GBM
      microvasculature. The contribution of endogenous brain pericytes to the tumor
      vasculature in GBM is, however, unclear. In this study, we determine the site of
      activation and the extent of contribution of endogenous brain pericytes to the
      GBM vasculature. GL261 mouse glioma was orthotopically implanted in mice
      expressing green fluorescent protein (GFP) under the pericyte marker regulator of
      G protein signaling 5 (RGS5). Host pericytes were not only activated within the
      glioma, but also in cortical areas overlying the tumor, the ipsilateral
      subventricular zone and within the hemisphere contralateral to the tumor. The
      host-derived activated pericytes that infiltrated the glioma were mainly
      localized to the tumor vessel wall. Infiltrating GFP positive pericytes co
      expressed the pericyte markers platelet-derived growth factor receptor-beta
      (PDGFR-beta) and neuron-glial antigen 2. Interestingly, more than half of all
      PDGFR-beta positive pericytes within the tumor were contributed by the host
      brain. We did not find any evidence that RGS5 positive pericytes adopt another
      phenotype within glioma in this paradigm. We conclude that endogenous pericytes
      become activated in widespread areas of the brain in response to an orthotopic
      mouse glioma. Host pericytes are recruited into the tumor and constitute a major
      part of the tumor pericyte population. 

PMID- 25875290
TI  - Sevoflurane inhibits nuclear factor-kappaB activation in lipopolysaccharide
      induced acute inflammatory lung injury via toll-like receptor 4 signaling.
AB  - BACKGROUND: Infection is a common cause of acute lung injury (ALI). This study
      was aimed to explore whether Toll-like receptors 4 (TLR4) of airway smooth muscle
      cells (ASMCs) play a role in lipopolysaccharide (LPS)-induced airway
      hyperresponsiveness and potential mechanisms. METHODS: In vivo: A sensitizing
      dose of LPS (50 ug) was administered i.p. to female mice before anesthesia with
      either 3% sevoflurane or phenobarbital i.p. After stabilization, the mice were
      challenged with 5 ug of intratracheal LPS to mimic inflammatory attack. The
      effects of sevoflurane were assessed by measurement of airway responsiveness to
      methacholine, histological examination, and IL-1, IL-6, TNF-alpha levels in
      bronchoalveolar lavage fluid (BALF). Protein and gene expression of TLR4 and NF
      kappaB were also assessed. In vitro: After pre-sensitization of ASMCs and ASM
      segments for 24h, levels of TLR4 and NF-kappaB proteins in cultured ASMCs were
      measured after continuous LPS exposure for 1, 3, 5, 12 and 24h in presence or
      absence of sevoflurane. Constrictor and relaxant responsiveness of ASM was
      measured 24 h afterwards. RESULTS: The mRNA and protein levels of NF-kappaB and
      TLR4 in ASM were increased and maintained at high level after LPS challenge
      throughout 24h observation period, both in vivo and in vitro. Sevoflurane reduced
      LPS-induced airway hyperresponsiveness, lung inflammatory cell infiltration and
      proinflammatory cytokines release in BALF as well as maximal isometric
      contractile force of ASM segments to acetylcholine, but it increased maximal
      relaxation response to isoproterenol. Treatment with specific NF-kappaB inhibitor
      produced similar protections as sevoflurane, including decreased expressions of
      TLR4 and NF-kappaB in cultured ASMCs and improved pharmacodynamic responsiveness
      of ASM to ACh and isoproterenol. CONCLUSIONS: This study demonstrates the crucial
      role of TLR4 activation in ASMCs during ALI in response to LPS. Sevoflurane
      exerts direct relaxant and anti-inflammatory effects in vivo and in vitro via
      inhibition of TLR4/NF-kappaB pathway.

PMID- 25875292
TI  - Bioaccumulation and trophic transfer of mercury and selenium in african sub
      tropical fluvial reservoirs food webs (Burkina Faso).
AB  - The bioaccumulation and biomagnification of mercury (Hg) and selenium (Se) were
      investigated in sub-tropical freshwater food webs from Burkina Faso, West Africa,
      a region where very few ecosystem studies on contaminants have been performed.
      During the 2010 rainy season, samples of water, sediment, fish, zooplankton, and
      mollusks were collected from three water reservoirs and analysed for total Hg
      (THg), methylmercury (MeHg), and total Se (TSe). Ratios of delta13C and delta15N
      were measured to determine food web structures and patterns of contaminant
      accumulation and transfer to fish. Food chain lengths (FCLs) were calculated
      using mean delta15N of all primary consumer taxa collected as the site-specific
      baseline. We report relatively low concentrations of THg and TSe in most fish. We
      also found in all studied reservoirs short food chain lengths, ranging from 3.3
      to 3.7, with most fish relying on a mixture of pelagic and littoral sources for
      their diet. Mercury was biomagnified in fish food webs with an enrichment factor
      ranging from 2.9 to 6.5 for THg and from 2.9 to 6.6 for MeHg. However, there was
      no evidence of selenium biomagnification in these food webs. An inverse
      relationship was observed between adjusted delta15N and log-transformed Se:Hg
      ratios, indicating that Se has a lesser protective effect in top predators, which
      are also the most contaminated animals with respect to MeHg. Trophic position,
      carbon source, and fish total length were the factors best explaining Hg
      concentration in fish. In a broader comparison of our study sites with literature
      data for other African lakes, the THg biomagnification rate was positively
      correlated with FCL. We conclude that these reservoir systems from tropical
      Western Africa have low Hg biomagnification associated with short food chains.
      This finding may partly explain low concentrations of Hg commonly reported in
      fish from this area. 

PMID- 25875291
TI  - The aspartate-less receiver (ALR) domains: distribution, structure and function.
AB  - Two-component signaling systems are ubiquitous in bacteria, Archaea and plants
      and play important roles in sensing and responding to environmental stimuli. To
      propagate a signaling response the typical system employs a sensory histidine
      kinase that phosphorylates a Receiver (REC) domain on a conserved aspartate (Asp)
      residue. Although it is known that some REC domains are missing this Asp residue,
      it remains unclear as to how many of these divergent REC domains exist, what
      their functional roles are and how they are regulated in the absence of the
      conserved Asp. Here we have compiled all deposited REC domains missing their
      phosphorylatable Asp residue, renamed here as the Aspartate-Less Receiver (ALR)
      domains. Our data show that ALRs are surprisingly common and are enriched for
      when attached to more rare effector outputs. Analysis of our informatics and the
      available ALR atomic structures, combined with structural, biochemical and
      genetic data of the ALR archetype RitR from Streptococcus pneumoniae presented
      here suggest that ALRs have reorganized their active pockets to instead take on a
      constitutive regulatory role or accommodate input signals other than Asp
      phosphorylation, while largely retaining the canonical post-phosphorylation
      mechanisms and dimeric interface. This work defines ALRs as an atypical REC
      subclass and provides insights into shared mechanisms of activation between ALR
      and REC domains. 

PMID- 25875293
TI  - Density-dependent natal dispersal patterns in a leopard population recovering
      from over-harvest.
AB  - Natal dispersal enables population connectivity, gene flow and metapopulation
      dynamics. In polygynous mammals, dispersal is typically male-biased. Classically,
      the 'mate competition', 'resource competition' and 'resident fitness' hypotheses
      predict density-dependent dispersal patterns, while the 'inbreeding avoidance'
      hypothesis posits density-independent dispersal. In a leopard (Panthera pardus)
      population recovering from over-harvest, we investigated the effect of sex,
      population density and prey biomass, on age of natal dispersal, distance
      dispersed, probability of emigration and dispersal success. Over an 11-year
      period, we tracked 35 subadult leopards using VHF and GPS telemetry. Subadult
      leopards initiated dispersal at 13.6 +/- 0.4 months. Age at commencement of
      dispersal was positively density-dependent. Although males (11.0 +/- 2.5 km)
      generally dispersed further than females (2.7 +/- 0.4 km), some males exhibited
      opportunistic philopatry when the population was below capacity. All 13 females
      were philopatric, while 12 of 22 males emigrated. Male dispersal distance and
      emigration probability followed a quadratic relationship with population density,
      whereas female dispersal distance was inversely density-dependent. Eight of 12
      known-fate females and 5 of 12 known-fate male leopards were successful in
      settling. Dispersal success did not vary with population density, prey biomass,
      and for males, neither between dispersal strategies (philopatry vs. emigration).
      Females formed matrilineal kin clusters, supporting the resident fitness
      hypothesis. Conversely, mate competition appeared the main driver for male
      leopard dispersal. We demonstrate that dispersal patterns changed over time, i.e.
      as the leopard population density increased. We conclude that conservation
      interventions that facilitated local demographic recovery in the study area also
      restored dispersal patterns disrupted by unsustainable harvesting, and that this
      indirectly improved connectivity among leopard populations over a larger
      landscape. 

PMID- 25875294
TI  - Genetics, genomics and evolution of ergot alkaloid diversity.
AB  - The ergot alkaloid biosynthesis system has become an excellent model to study
      evolutionary diversification of specialized (secondary) metabolites. This is a
      very diverse class of alkaloids with various neurotropic activities, produced by
      fungi in several orders of the phylum Ascomycota, including plant pathogens and
      protective plant symbionts in the family Clavicipitaceae. Results of comparative
      genomics and phylogenomic analyses reveal multiple examples of three evolutionary
      processes that have generated ergot-alkaloid diversity: gene gains, gene losses,
      and gene sequence changes that have led to altered substrates or product
      specificities of the enzymes that they encode (neofunctionalization). The
      chromosome ends appear to be particularly effective engines for gene gains,
      losses and rearrangements, but not necessarily for neofunctionalization. Changes
      in gene expression could lead to accumulation of various pathway intermediates
      and affect levels of different ergot alkaloids. Genetic alterations associated
      with interspecific hybrids of Epichloe species suggest that such variation is
      also selectively favored. The huge structural diversity of ergot alkaloids
      probably represents adaptations to a wide variety of ecological situations by
      affecting the biological spectra and mechanisms of defense against herbivores, as
      evidenced by the diverse pharmacological effects of ergot alkaloids used in
      medicine.

PMID- 25875296
TI  - A priori data-driven multi-clustered reservoir generation algorithm for echo
      state network.
AB  - Echo state networks (ESNs) with multi-clustered reservoir topology perform better
      in reservoir computing and robustness than those with random reservoir topology.
      However, these ESNs have a complex reservoir topology, which leads to
      difficulties in reservoir generation. This study focuses on the reservoir
      generation problem when ESN is used in environments with sufficient priori data
      available. Accordingly, a priori data-driven multi-cluster reservoir generation
      algorithm is proposed. The priori data in the proposed algorithm are used to
      evaluate reservoirs by calculating the precision and standard deviation of ESNs.
      The reservoirs are produced using the clustering method; only the reservoir with
      a better evaluation performance takes the place of a previous one. The final
      reservoir is obtained when its evaluation score reaches the preset requirement.
      The prediction experiment results obtained using the Mackey-Glass chaotic time
      series show that the proposed reservoir generation algorithm provides ESNs with
      extra prediction precision and increases the structure complexity of the network.
      Further experiments also reveal the appropriate values of the number of clusters
      and time window size to obtain optimal performance. The information entropy of
      the reservoir reaches the maximum when ESN gains the greatest precision. 

PMID- 25875295
TI  - Role of acidic residues in helices TH8-TH9 in membrane interactions of the
      diphtheria toxin T domain.
AB  - The pH-triggered membrane insertion of the diphtheria toxin translocation domain
      (T domain) results in transferring the catalytic domain into the cytosol, which
      is relevant to potential biomedical applications as a cargo-delivery system.
      Protonation of residues is suggested to play a key role in the process, and
      residues E349, D352 and E362 are of particular interest because of their location
      within the membrane insertion unit TH8-TH9. We have used various spectroscopic,
      computational and functional assays to characterize the properties of the T
      domain carrying the double mutation E349Q/D352N or the single mutation E362Q.
      Vesicle leakage measurements indicate that both mutants interact with the
      membrane under less acidic conditions than the wild-type. Thermal unfolding and
      fluorescence measurements, complemented with molecular dynamics simulations,
      suggest that the mutant E362Q is more susceptible to acid destabilization because
      of disruption of native intramolecular contacts. Fluorescence experiments show
      that removal of the charge in E362Q, and not in E349Q/D352N, is important for
      insertion of TH8-TH9. Both mutants adopt a final functional state upon further
      acidification. We conclude that these acidic residues are involved in the pH
      dependent action of the T domain, and their replacements can be used for fine
      tuning the pH range of membrane interactions.

PMID- 25875297
TI  - Effects of beta-alanine supplementation on brain homocarnosine/carnosine signal
      and cognitive function: an exploratory study.
AB  - OBJECTIVES: Two independent studies were conducted to examine the effects of 28 d
      of beta-alanine supplementation at 6.4 g d(-1) on brain homocarnosine/carnosine
      signal in omnivores and vegetarians (Study 1) and on cognitive function before
      and after exercise in trained cyclists (Study 2). METHODS: In Study 1, seven
      healthy vegetarians (3 women and 4 men) and seven age- and sex-matched omnivores
      undertook a brain 1H-MRS exam at baseline and after beta-alanine supplementation.
      In study 2, nineteen trained male cyclists completed four 20-Km cycling time
      trials (two pre supplementation and two post supplementation), with a battery of
      cognitive function tests (Stroop test, Sternberg paradigm, Rapid Visual
      Information Processing task) being performed before and after exercise on each
      occasion. RESULTS: In Study 1, there were no within-group effects of beta-alanine
      supplementation on brain homocarnosine/carnosine signal in either vegetarians (p
      = 0.99) or omnivores (p = 0.27); nor was there any effect when data from both
      groups were pooled (p = 0.19). Similarly, there was no group by time interaction
      for brain homocarnosine/carnosine signal (p = 0.27). In study 2, exercise
      improved cognitive function across all tests (P < 0.05), although there was no
      effect (P>0.05) of beta-alanine supplementation on response times or accuracy for
      the Stroop test, Sternberg paradigm or RVIP task at rest or after exercise.
      CONCLUSION: 28 d of beta-alanine supplementation at 6.4 g d(-1) appeared not to
      influence brain homocarnosine/carnosine signal in either omnivores or
      vegetarians; nor did it influence cognitive function before or after exercise in
      trained cyclists.

PMID- 25875298
TI  - The Trypanosoma cruzi vitamin C dependent peroxidase confers protection against
      oxidative stress but is not a determinant of virulence.
AB  - BACKGROUND: The neglected parasitic infection Chagas disease is rapidly becoming
      a globalised public health issue due to migration. There are only two anti
      parasitic drugs available to treat this disease, benznidazole and nifurtimox.
      Thus it is important to identify and validate new drug targets in Trypanosoma
      cruzi, the causative agent. T. cruzi expresses an ER-localised ascorbate
      dependent peroxidase (TcAPx). This parasite-specific enzyme has attracted
      interest from the perspective of targeted chemotherapy. METHODOLOGY/PRINCIPAL
      FINDINGS: To assess the importance of TcAPx in protecting T. cruzi from oxidative
      stress and to determine if it is essential for virulence, we generated null
      mutants by targeted gene disruption. Loss of activity was associated with
      increased sensitivity to exogenous hydrogen peroxide, but had no effect on
      susceptibility to the front-line Chagas disease drug benznidazole. This suggests
      that increased oxidative stress in the ER does not play a significant role in its
      mechanism of action. Homozygous knockouts could proceed through the entire life
      cycle in vitro, although they exhibited a significant decrease in their ability
      to infect mammalian cells. To investigate virulence, we exploited a highly
      sensitive bioluminescence imaging system which allows parasites to be monitored
      in real-time in the chronic stage of murine infections. This showed that
      depletion of enzyme activity had no effect on T. cruzi replication, dissemination
      or tissue tropism in vivo. CONCLUSIONS/SIGNIFICANCE: TcAPx is not essential for
      parasite viability within the mammalian host, does not have a significant role in
      establishment or maintenance of chronic infections, and should therefore not be
      considered a priority for drug design.

PMID- 25875299
TI  - Relative Importance of the Arcuate and Anteroventral Periventricular Kisspeptin
      Neurons in Control of Puberty and Reproductive Function in Female Rats.
AB  - Kisspeptin plays a critical role in pubertal timing and reproductive function. In
      rodents, kisspeptin perikarya within the hypothalamic arcuate (ARC) and
      anteroventral periventricular (AVPV) nuclei are thought to be involved in LH
      pulse and surge generation, respectively. Using bilateral microinjections of
      recombinant adeno-associated virus encoding kisspeptin antisense into the ARC or
      AVPV of female rats at postnatal day 10, we investigated the relative importance
      of these two kisspeptin populations in the control of pubertal timing, estrous
      cyclicity, and LH surge and pulse generation. A 37% knockdown of kisspeptin in
      the AVPV resulted in a significant delay in vaginal opening and first vaginal
      estrous, abnormal estrous cyclicity, and reduction in the occurrence of
      spontaneous LH surges, although these retained normal amplitude. This AVPV
      knockdown had no effect on LH pulse frequency, measured after ovariectomy. A 32%
      reduction of kisspeptin in the ARC had no effect on the onset of puberty but
      resulted in abnormal estrous cyclicity and decreased LH pulse frequency.
      Additionally, the knockdown of kisspeptin in the ARC decreased the amplitude but
      not the incidence of LH surges. These results might suggest that the role of AVPV
      kisspeptin in the control of pubertal timing is particularly sensitive to
      perturbation. In accordance with our previous studies, ARC kisspeptin signaling
      was critical for normal pulsatile LH secretion in female rats. Despite the widely
      reported role of AVPV kisspeptin neurons in LH surge generation, this study
      suggests that both AVPV and ARC populations are essential for normal LH surges
      and estrous cyclicity. 

PMID- 25875300
TI  - A functional dissection of PTEN N-terminus: implications in PTEN subcellular
      targeting and tumor suppressor activity.
AB  - Spatial regulation of the tumor suppressor PTEN is exerted through alternative
      plasma membrane, cytoplasmic, and nuclear subcellular locations. The N-terminal
      region of PTEN is important for the control of PTEN subcellular localization and
      function. It contains both an active nuclear localization signal (NLS) and an
      overlapping PIP2-binding motif (PBM) involved in plasma membrane targeting. We
      report a comprehensive mutational and functional analysis of the PTEN N-terminus,
      including a panel of tumor-related mutations at this region. Nuclear/cytoplasmic
      partitioning in mammalian cells and PIP3 phosphatase assays in reconstituted S.
      cerevisiae defined categories of PTEN N-terminal mutations with distinct PIP3
      phosphatase and nuclear accumulation properties. Noticeably, most tumor-related
      mutations that lost PIP3 phosphatase activity also displayed impaired nuclear
      localization. Cell proliferation and soft-agar colony formation analysis in
      mammalian cells of mutations with distinctive nuclear accumulation and catalytic
      activity patterns suggested a contribution of both properties to PTEN tumor
      suppressor activity. Our functional dissection of the PTEN N-terminus provides
      the basis for a systematic analysis of tumor-related and experimentally
      engineered PTEN mutations. 

PMID- 25875301
TI  - Dynamic filopodia are required for chemokine-dependent intracellular polarization
      during guided cell migration in vivo.
AB  - Cell migration and polarization is controlled by signals in the environment.
      Migrating cells typically form filopodia that extend from the cell surface, but
      the precise function of these structures in cell polarization and guided
      migration is poorly understood. Using the in vivo model of zebrafish primordial
      germ cells for studying chemokine-directed single cell migration, we show that
      filopodia distribution and their dynamics are dictated by the gradient of the
      chemokine Cxcl12a. By specifically interfering with filopodia formation, we
      demonstrate for the first time that these protrusions play an important role in
      cell polarization by Cxcl12a, as manifested by elevation of intracellular pH and
      Rac1 activity at the cell front. The establishment of this polarity is at the
      basis of effective cell migration towards the target. Together, we show that
      filopodia allow the interpretation of the chemotactic gradient in vivo by
      directing single-cell polarization in response to the guidance cue. 

PMID- 25875303
TI  - Time to rethink the systematic review catechism? Moving from 'what works' to
      'what happens'.
AB  - Systematic review methods are developing rapidly, and most researchers would
      recognise their key methodological aspects, such as a closely focussed question,
      a comprehensive search, and a focus on synthesising 'stronger' rather than
      'weaker' evidence. However, it may be helpful to question some of these
      underlying principles, because while they work well for simpler review questions,
      they may result in overly narrow approaches to more complex questions and
      interventions. This commentary discusses some core principles of systematic
      reviews, and how they may require further rethinking, particularly as reviewers
      turn their attention to increasingly complex issues, where a Bayesian perspective
      on evidence synthesis, which would aim to assemble evidence - of different types,
      if necessary - in order to inform decisions', may be more productive than the
      'traditional' systematic review model. Among areas identified for future research
      are the examination of publication bias in qualitative research; research on the
      efficiency and potential biases of comprehensive searches in different
      disciplines; and the use of Bayesian methods in evidence synthesis. The
      incorporation of a systems perspective into systematic reviews is also an area
      which needs rapid development. 

PMID- 25875302
TI  - Insights into mammalian biology from the wild house mouse Mus musculus.
AB  - The house mouse, Mus musculus, was established in the early 1900s as one of the
      first genetic model organisms owing to its short generation time, comparatively
      large litters, ease of husbandry, and visible phenotypic variants. For these
      reasons and because they are mammals, house mice are well suited to serve as
      models for human phenotypes and disease. House mice in the wild consist of at
      least three distinct subspecies and harbor extensive genetic and phenotypic
      variation both within and between these subspecies. Wild mice have been used to
      study a wide range of biological processes, including immunity, cancer, male
      sterility, adaptive evolution, and non-Mendelian inheritance. Despite the
      extensive variation that exists among wild mice, classical laboratory strains are
      derived from a limited set of founders and thus contain only a small subset of
      this variation. Continued efforts to study wild house mice and to create new
      inbred strains from wild populations have the potential to strengthen house mice
      as a model system. 

PMID- 25875304
TI  - Specific uptake and genotoxicity induced by polystyrene nanobeads with distinct
      surface chemistry on human lung epithelial cells and macrophages.
AB  - Nanoparticle surface chemistry is known to play a crucial role in interactions
      with cells and their related cytotoxic effects. As inhalation is a major route of
      exposure to nanoparticles, we studied specific uptake and damages of well
      characterized fluorescent 50 nm polystyrene (PS) nanobeads harboring different
      functionalized surfaces (non-functionalized, carboxylated and aminated) on
      pulmonary epithelial cells and macrophages (Calu-3 and THP-1 cell lines
      respectively). Cytotoxicity of in mass dye-labeled functionalized PS nanobeads
      was assessed by xCELLigence system and alamarBlue viability assay. Nanobeads
      cells interactions were studied by video-microscopy, flow cytometry and also
      confocal microscopy. Finally ROS generation was assessed by glutathione depletion
      dosages and genotoxicity was assessed by gamma-H2Ax foci detection, which is
      considered as the most sensitive technique for studying DNA double strand breaks.
      The uptake kinetic was different for each cell line. All nanobeads were partly
      adsorbed and internalized, then released by Calu-3 cells, while THP-1 macrophages
      quickly incorporated all nanobeads which were located in the cytoplasm rather
      than in the nuclei. In parallel, the genotoxicity study reported that only
      aminated nanobeads significantly increased DNA damages in association with a
      strong depletion of reduced glutathione in both cell lines. We showed that for
      similar nanoparticle concentrations and sizes, aminated polystyrene nanobeads
      were more cytotoxic and genotoxic than unmodified and carboxylated ones on both
      cell lines. Interestingly, aminated polystyrene nanobeads induced similar
      cytotoxic and genotoxic effects on Calu-3 epithelial cells and THP-1 macrophages,
      for all levels of intracellular nanoparticles tested. Our results strongly
      support the primordial role of nanoparticles surface chemistry on cellular uptake
      and related biological effects. Moreover our data clearly show that nanoparticle
      internalization and observed adverse effects are not necessarily associated. 

PMID- 25875305
TI  - Comprehensive evaluation of Toxoplasma gondii VEG and Neospora caninum LIV
      genomes with tachyzoite stage transcriptome and proteome defines novel transcript
      features.
AB  - Toxoplasma gondii is an important protozoan parasite that infects all warm
      blooded animals and causes opportunistic infections in immuno-compromised humans.
      Its closest relative, Neospora caninum, is an important veterinary pathogen that
      causes spontaneous abortion in livestock. Comparative genomics of these two
      closely related coccidians has been of particular interest to identify genes that
      contribute to varied host cell specificity and disease. Here, we describe a
      manual evaluation of these genomes based on strand-specific RNA sequencing and
      shotgun proteomics from the invasive tachyzoite stages of these two parasites. We
      have corrected predicted structures of over one third of the previously annotated
      gene models and have annotated untranslated regions (UTRs) in over half of the
      predicted protein-coding genes. We observe distinctly long UTRs in both the
      organisms, almost four times longer than other model eukaryotes. We have also
      identified a putative set of cis-natural antisense transcripts (cis-NATs) and
      long intergenic non-coding RNAs (lincRNAs). We have significantly improved the
      annotation quality in these genomes that would serve as a manually curated
      dataset for Toxoplasma and Neospora research communities. 

PMID- 25875306
TI  - The value of blood oxygenation level-dependent (BOLD) MR imaging in
      differentiation of renal solid mass and grading of renal cell carcinoma (RCC):
      analysis based on the largest cross-sectional area versus the entire whole
      tumour.
AB  - OBJECTIVES: To study the value of assessing renal masses using different methods
      in parameter approaches and to determine whether BOLD MRI is helpful in
      differentiating RCC from benign renal masses, differentiating clear-cell RCC from
      renal masses other than clear-cell RCC and determining the tumour grade. METHODS:
      Ninety-five patients with 139 renal masses (93 malignant and 46 benign) who
      underwent abdominal BOLD MRI were enrolled. R2* values were derived from the
      largest cross-section (R2*largest) and from the whole tumour (R2*whole). Intra
      observer and inter-observer agreements were analysed based on two measurements by
      the same observer and the first measurement from each observer, respectively, and
      these agreements are reported with intra-class correlation coefficients and 95%
      confidence intervals. The diagnostic value of the R2* value in the evaluation was
      assessed with receiver-operating characteristic analysis. RESULTS: The intra
      observer agreement was very good for R2*largest and R2*whole (all > 0.8). The
      inter-observer agreement of R2*whole (0.75, 95% confidence interval: 0.69~0.79)
      was good and was significantly improved compared with the R2*largest (0.61, 95%
      confidence interval: 0.52~0.68), as there was no overlap in the 95% confidence
      interval of the intra-class correlation coefficients. The diagnostic value in
      differentiating renal cell carcinoma from benign lesions with R2*whole
      (AUC=0.79/0.78[observer1/observer2]) and R2*largest (AUC=0.75[observer1]) was
      good and significantly higher (p=0.01 for R2*largest[observer2] vs
      R2*whole[observer2], p<0.01 for R2*whole[observer1] vs R2*largest[observer2])
      than R2*largest for observer 2 (AUC=0.64). For the grading of clear-cell RCC,
      both R2*whole and R2*largest were good (all > 0.7) and were not significantly
      different (p=0.89/0.93 for R2*largest vs R2*whole[observer1/observer2], 0.96 for
      R2*whole[observer1] vs R2*largest[observer2] and 0.96 for R2*whole [observer2] vs
      R2*largest[observer1]). CONCLUSIONS: BOLD MRI could provide a feasible parameter
      for differentiating renal cell carcinoma from benign renal masses and for
      predicting clear-cell renal cell carcinoma grading. Compared with the largest
      cross-section, assessing the whole tumour provides better inter-observer
      agreement in parameter measurement for differentiating renal cell carcinoma from
      benign renal masses.

PMID- 25875307
TI  - Mentorship in nursing academia: a systematic review protocol.
AB  - BACKGROUND: Mentorship is perceived as vital to attracting, training, and
      retaining nursing faculty members and to maintaining high-quality education
      programs. While there is emerging evidence to support the value of mentorship in
      academic medicine, the extant state of the evidence for mentorship in nursing
      academia has not been established. We describe a protocol for a mixed-methods
      systematic review to critically appraise the evidence for mentorship in nursing
      academia. METHODS: Studies examining the effectiveness of mentorship
      interventions with nursing faculty who teach in registered nursing education
      programs will be included. Mentee, mentor, and nursing education institutional
      outcomes will be explored. Quantitative, qualitative, and mixed method studies
      will be eligible for inclusion, without restrictions on publication status, year
      of publication, or language. We will search electronic databases (for example,
      MEDLINE, CINAHL, ERIC) and gray literature (for example, conference proceedings,
      key journals, relevant organizational websites) for relevant citations. Using
      pilot-tested screening and data extraction forms, two reviewers will
      independently review the studies in three steps: (1) abstract/title screening,
      (2) full-text screening of accepted studies, and (3) data extraction of accepted
      studies. Studies will be aggregated for meta-synthesis (qualitative) and meta
      analysis (quantitative), should the data permit. DISCUSSION: This study is the
      first systematic review of existing global evidence for mentorship in nursing
      academia. It will help identify key evidence gaps and inform the development and
      implementation of mentorship interventions. The mentorship outcomes that result
      from this review could be used to guide the practice of mentorship to increase
      positive outcomes for nursing faculty and the students they teach and ultimately
      effect improvements for the patients they care for. This review will also
      identify key considerations for future research on mentorship in nursing academia
      and the enhancement of nursing science.

PMID- 25875308
TI  - Influence of periodontal tissue thickness on buccal plate remodelling on
      immediate implants with xenograft.
AB  - AIM: To evaluate the influence of gingival thickness and bone grafting on buccal
      bone plate remodelling after immediate implant placement in sockets with thin
      buccal bone, using a flapless approach. MATERIALS AND METHODS: The gingiva of
      eight dogs was thinned at one side of the mandible, mandibular premolars were
      extracted without flaps, and four implants were installed on each side at 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). After 12 weeks the dogs were
      sacrificed and the samples were processed for histological analysis. RESULTS: All
      animals exhibited a thin buccal bone initially. In all the experimental groups
      the buccal gap was filled with newly formed bone and the buccal bone level was
      slightly apical to the implant shoulder. There were no statistically significant
      differences among the groups for the histomorphometric parameters. CONCLUSIONS:
      The thickness of the buccal bone was a fundamental factor in buccal bone plate
      resorption, even with flapless implantation. The gingival thickness or the
      addition of a biomaterial in the gap did not influence the results.

PMID- 25875309
TI  - Experimental and first-principles investigation of the adsorption and entrapping
      of guanine with SiO2 clusters of sol-gel silicate material for understanding DNA
      photodamage.
AB  - We report a first principles density functional theoretical (DFT) investigation
      of guanine (G) adsorption onto SiO2 clusters, viz., Si2O4, Si3O6, Si4O8 and
      Si5O10 in terms of geometry, binding energy (EB), binding site, energy gap (Eg),
      and electronic and spectral properties. Guanine entrapped within a Si9O18 cluster
      was also studied in terms of geometry, energy gap (Eg), electronic and spectral
      properties. We observed that the most stable forms of the cluster were Si5O10 and
      Si9O18. Guanine adsorbed onto SiO2 (G-SiO2) and guanine entrapped within SiO2 (GE
      SiO2) were analyzed by the B3LYP/LanL2DZ method. The HOMO-LUMO energies
      illustrate that charge transfer from ligand to metal (L -> M) occurs in G-SiO2
      clusters as guanine to SiO2. The composite of guanine with nanostructured silica
      material was prepared by simple precipitation and chemical sol-gel processes. The
      prepared G-SiO2 and GE-SiO2 composites were characterized by FT-IR and FE-SEM
      with EDX analysis. The resulting experimental evidence is included for better
      understanding the guanine adsorption and entrapment. The adsorption and
      entrapping of G-SiO2 and GE-SiO2 was also confirmed by UV-vis spectroscopy.
      Experimental results are compared with the DFT results. Furthermore, the sol-gel
      silicate material used to protect the DNA base (guanine) from UVA-irradiation has
      been highlighted. 

PMID- 25875311
TI  - Bioactive Maleic Anhydrides and Related Diacids from the Aquatic Hyphomycete
      Tricladium castaneicola.
AB  - Four maleic anhydride derivatives, tricladolides A-D (1-4), and three alkylidene
      succinic acid derivatives, tricladic acids A-C (5-7), were isolated from the
      aquatic hyphomycete Tricladium castaneicola. The structures of these compounds
      were determined by spectroscopic analysis, and all were found to be novel. The
      compounds exhibited inhibitory activity against fungi, particularly Phytophthora
      sp., a plant pathogen of oomycetes. The inhibitory activity of these metabolites
      revealed the importance of the cyclic anhydride structure and the lipophilicity
      of the alkyl side chain. On the other hand, the cytotoxicity of the compounds
      against B16 melanoma cells indicated that the cyclic anhydride structure was not
      essential. 

PMID- 25875310
TI  - Effect of depression and diabetes mellitus on the risk for dementia: a national
      population-based cohort study.
AB  - IMPORTANCE: Although depression and type 2 diabetes mellitus (DM) may
      independently increase the risk for dementia, no studies have examined whether
      the risk for dementia among people with comorbid depression and DM is higher than
      the sum of each exposure individually. OBJECTIVE: To examine the risk for all
      cause dementia among persons with depression, DM, or both compared with persons
      with neither exposure. DESIGN, SETTING, AND PARTICIPANTS: We performed a national
      population-based cohort study of 2 454 532 adults, including 477 133 (19.4%) with
      depression, 223 174 (9.1%) with DM, and 95 691 (3.9%) with both. We included all
      living Danish citizens 50 years or older who were free of dementia from January
      1, 2007, through December 31, 2013 (followed up through December 31, 2013).
      Dementia was ascertained by physician diagnosis from the Danish National Patient
      Register or the Danish Psychiatric Central Register and/or by prescription of a
      cholinesterase inhibitor or memantine hydrochloride from the Danish National
      Prescription Registry. Depression was ascertained by psychiatrist diagnosis from
      the Danish Psychiatric Central Research Register or by prescription of an
      antidepressant from the Danish National Prescription Registry. Diabetes mellitus
      was identified using the National Diabetes Register. MAIN OUTCOMES AND MEASURES:
      We estimated the risk for all-cause dementia associated with DM, depression, or
      both using Cox proportional hazards regression models that adjusted for potential
      confounding factors (eg, demographics) and potential intermediates (eg, medical
      comorbidities). RESULTS: During 13 834 645 person-years of follow-up, 59 663
      participants (2.4%) developed dementia; of these, 6466 (10.8%) had DM, 15 729
      (26.4%) had depression, and 4022 (6.7%) had both. The adjusted hazard ratio for
      developing all-cause dementia was 1.83 (95% CI, 1.80-1.87) for persons with
      depression, 1.20 (95% CI, 1.17-1.23) for persons with DM, and 2.17 (95% CI, 2.10
      2.24) for those with both compared with persons who had neither exposure. The
      excess risk for all-cause dementia observed for individuals with comorbid
      depression and DM surpassed the summed risk associated with each exposure
      individually, especially for persons younger than 65 years (hazard ratio, 4.84
      [95% CI, 4.21-5.55]). The corresponding attributable proportion due to the
      interaction of comorbid depression and DM was 0.25 (95% CI, 0.13-0.36; P < .001)
      for those younger than 65 years and 0.06 (95% CI, 0.02-0.10; P = .001) for those
      65 years or older. CONCLUSIONS AND RELEVANCE: Depression and DM were
      independently associated with a greater risk for dementia, and the combined
      association of both exposures with the risk for all-cause dementia was stronger
      than the additive association.

PMID- 25875313
TI  - Rational Design of Multiamphiphilic Polymer Compatibilizers: Versatile Solubility
      and Hybridization of Noncovalently Functionalized CNT Nanocomposites.
AB  - The design of amphiphilic polymer compatibilizers for solubility manipulation of
      CNT composites was systematically generalized in this study. Structurally
      tailored multiamphiphilic compatibilizer were designed and synthesized by
      applying simple, high-yield reactions. This multiamphiphilic compatibilizer was
      applied for noncovalent functionalization of CNTs as well as provided CNTs with
      outstanding dispersion stability, manipulation of solubility, and hybridization
      with Ag nanoparticles (NPs). With regard to the dispersion properties, superior
      records in maximum concentration (2.88-3.10 mg/mL in chloroform), and mass ratio
      of the compatibilizer for good CNT dispersion (36 wt %) were achieved by MWCNTs
      functionalized with a multiamphiphilic block copolymer compatibilizer. In
      particular, the solubility limitations of MWCNT dispersion in solvents ranging
      from toluene (nonpolar) to aqueous solution (polar) are surprisingly resolved by
      introducing this multiamphiphilic polymer compatibilizer. Furthermore, this
      polymer compatibilizer allowed the synthesis of the hybrid CNT nanocomposites
      with Ag nanoparticles by an in situ nucleation process. As such, the
      multiamphiphilic compatibilizer candidate as a new concept for the noncovalent
      functionalization of CNTs can extend their use for a wide range of applications. 

PMID- 25875312
TI  - Design and Synthesis of Amphiphilic and Luminescent Tris-Cyclometalated
      Iridium(III) Complexes Containing Cationic Peptides as Inducers and Detectors of
      Cell Death via a Calcium-Dependent Pathway.
AB  - Cationic amphiphilic peptides have the potential to function as agents for the
      treatment of microbial infections and cancer therapy. The cationic and
      hydrophobic parts of these molecules allow them to associate strongly with
      negatively charged bacterial or cancer cell membranes, thus exerting
      antimicrobial and anticancer activities through membrane disruption. Meanwhile,
      cyclometalated iridium(III) complexes such as fac-Ir(ppy)3 (ppy = 2
      phenylpyridine) and fac-Ir(tpy)3 (tpy = 2-(4'-tolyl)pyridine) possess C3
      symmetric structures and excellent photophysical properties as phosphorescence
      materials, which make them important candidates for use in biological
      applications such as chemosensors, biolabeling, living cell staining, in vivo
      tumor imaging, and anticancer agents. We recently reported on some regioselective
      substitution reactions of Ir(tpy)3 and Ir(ppy)3 at the 5'-position (p-position
      with respect to the C-Ir bond) on the 2-phenylpyridine ligands and their
      subsequent conversions to a variety of functional groups. We report here on the
      design and synthesis of amphiphilic and luminescent tris-cyclometalated Ir
      complexes in which cationic peptides are attached through alkyl chain linkers
      that work as inducers and detectors of cell death. Ir complexes containing
      cationic peptides such as a KKGG sequence and alkyl chain linkers of adequate
      length (C6 and C8) exhibit considerable cytotoxicity against cancer cells such as
      Jurkat, Molt-4, HeLa-S3, and A549 cells, and that dead cells are well stained
      with these Ir complexes. Furthermore, an Ir complex in which the KKGG peptide is
      attached through a C6 linker displayed lower cytotoxicity against normal mouse
      lymphocytes. Mechanistic studies suggest that Ir complexes containing the KKGG
      peptide interact with anionic molecules on the cell surface and/or membrane
      receptors to trigger the Ca(2+) dependent pathway and intracellular Ca(2+)
      response, resulting in necrosis accompanied by membrane disruption. 

PMID- 25875315
TI  - Urinary Incontinence and Levels of Regular Physical Exercise in Young Women.
AB  - The purpose of this study was to determine the influence of different levels of
      regular physical exercise on the frequency of urinary incontinence in young
      nulliparous women from the northern region of Portugal. Participants (n=386) self
      reported demographic variables, frequency, and time spent practicing organized
      exercise per week, as well as completed the International Consultation on
      Incontinence Questionnaire-Short Form. The level of exercise was calculated based
      on the time (in minutes) usually spent per week in organized exercise. 19.9% of
      Portuguese nulliparous women reported incontinence symptoms. Considering the
      distribution of urinary incontinence among the different quartiles of organized
      exercise, women from the 4(th)quartile (those who train for competitive purposes)
      demonstrated highest relative frequency (p=0.000) and a 2.53 greater relative
      risk to develop (95% CIs,1.3-2.7) incontinence compared to women from the 1(st)
      quartile (inactive). Women who practice exercise for recreational purposes (2(nd)
      and 3(rd) quartiles) did not show significant differences in the urinary
      incontinence prevalence and relative risk of developing it compared to women from
      the 1(st) quartile. The results showed that women participating in organized
      exercise involving high volume training for competition are potentially at risk
      of developing urinary incontinence, although organized exercise undertaken
      without the intent to compete seems to be safe for maintaining urinary
      continence. 

PMID- 25875314
TI  - High nitric oxide production, secondary to inducible nitric oxide synthase
      expression, is essential for regulation of the tumour-initiating properties of
      colon cancer stem cells.
AB  - Chronic inflammation is a leading cause of neoplastic transformation in many
      human cancers and especially in colon cancer (CC), in part due to tumour
      promotion by nitric oxide (NO) generated at inflammatory sites. It has also been
      suggested that high NO synthesis, secondary to inducible NO synthase (iNOS)
      expression, is a distinctive feature of cancer stem cells (CSCs), a small subset
      of tumour cells with self-renewal capacity. In this study we explored the
      contribution of NO to the development of colon CSC features and evaluated
      potential strategies to treat CC by modulating NO production. Our data show an
      integral role for endogenous NO and iNOS activity in the biology of colon CSCs.
      Indeed, colon CSCs with high endogenous NO production (NO(high)) displayed higher
      tumourigenic abilities than NO(low) fractions. The blockade of endogenous NO
      availability, using either a specific iNOS inhibitor or a genetic knock-down of
      iNOS, resulted in a significant reduction of colon CSC tumourigenic capacities in
      vitro and in vivo. Interestingly, analysis of genes altered by iNOS-directed
      shRNA showed that the knockdown of iNOS expression was associated with a
      significant down-regulation of signalling pathways involved in stemness and
      tumour progression in colon CSCs. These findings confirm that endogenous NO plays
      an important role in defining the stemness properties of colon CSCs through cross
      regulation of several cellular signalling pathways. This discovery could shed
      light on the mechanisms by which NO induces the growth and invasiveness of CC,
      providing new insights into the link between inflammation and colon
      tumourigenesis.

PMID- 25875316
TI  - Essential Hypertension: Cardiovascular Response to Breath Hold Combined with
      Exercise.
AB  - Essential hypertension (EH) is a widespread disease and might be prevalent in
      apnea divers and master athletes. Little is known about the influence of EH and
      the antihypertensive drugs (AHD) on cardiovascular reactions to combined breath
      hold (BH) and exercise. In this pilot study, healthy divers (HCON) were compared
      with treated hypertensive divers with regard to heart rate (HR) and mean blood
      pressure (MAP) responses to BH, exercise and the combination of both. Ten
      subjects with EH and ten healthy divers were tested. 3 different 20 s stimuli
      were applied: BH combined with 30 W or 150 W and 150 W without BH. The time
      charts during the stress intervals and during recovery were compared. Subjects
      treated with an angiotensin-converting enzyme (ACE) inhibitor showed higher
      changes for MAP values if breath hold was performed. HR responses were obviously
      changed if a beta-blocker was part of the medication. One subject showed extreme
      MAP responses to all stimuli and conspicuous HR if BH was involved. The
      modulation of HR-/MAP-response in EH subjects depends on the mechanisms of
      antihypertensive agents. The combination of an ACE inhibitor and a beta-blocker
      may give the best protection. It is recommended to include short apnea tests in
      the fitness-to-dive examination to individually predict potential endangerment. 

PMID- 25875317
TI  - Independent Association of Muscular Strength and Carotid Intima-Media Thickness
      in Children.
AB  - The aim of this cross-sectional study was to examine the influence of muscular
      strength on carotid intima-media thickness (cIMT) in children, controlling for
      the effect of cardiorespiratory fitness (CRF) and central adiposity and to
      examine if differences among muscular strength tertiles translate to
      physiological differences. We assessed cIMT of the common carotid artery in 366
      children between 11-12 years of age (191 girls). Measures included cIMT assessed
      with high-resolution ultrasonography, a maximal handgrip strength test, body fat
      mass and lean mass from DXA and CRF determined using a maximal cycle ergometer
      test. Association between muscular strength and cIMT adjusted for CRF and central
      adiposity, as measured by trunk fat, was tested with multiple linear regression
      analysis. Differences in risk factors among muscular strength groups were tested
      with ANOVA. The Muscular Strength Index (MSI) was inversely associated with cIMT
      independently of CRF and central adiposity (p<0.05). The low MSI group had the
      highest values of cIMT, waist circumference and systolic blood pressure and the
      lowest CRF (p<0.05). There was an inverse and independent association between
      muscular strength and cIMT. Low muscular strength was associated with higher
      levels of cardiovascular disease risk factors in children. 

PMID- 25875318
TI  - Evaluation of the Best-designed Graded Exercise Test to Assess Peak Treadmill
      Speed.
AB  - This study examined the influence of different speed increments during treadmill
      exercise tests on peak treadmill speed (Vpeak) and its relationship with a 1-h
      treadmill running performance. 18 male recreational and amateur runners (10-km
      running pace: 10-15 km.h(-1)) performed, in an alternate order, 3 continuous
      incremental exercise tests with different speed increments (0.5, 1.0 and 2.0
      km.h(-1)) on a motorized treadmill to determine Vpeak. Thereafter they undertook
      a 1-h time trial on a treadmill. Vpeak was determined as either (a) the highest
      speed that could be maintained for a complete minute (Vpeak-60 s), (b) the speed
      of the last complete stage (Vpeak-C), or (c) the speed of the last complete stage
      added to the product of the speed increment and the completed fraction of the
      incomplete stage (Vpeak-P). The Vpeak values were highly influenced by the
      different speed-incremented rates and the Vpeak-P determined during the protocol
      comprising speed increments of 1 km.h(-1) presented the highest correlation with
      1-h time trial performance (r=0.89). The results suggest that a protocol with
      speed increments comprising 1 km.h(-1) and with a 3-min stage duration should be
      used as standard for the determination of Vpeak to assess aerobic fitness and
      predict endurance performance in recreational runners. Furthermore, the Vpeak-P
      should be used for the determination of Vpeak. 

PMID- 25875319
TI  - Metal-free nitrogenation of 2-acetylbiphenyls: expeditious synthesis of
      phenanthridines.
AB  - An intermolecular nitrogenation reaction toward the synthesis of phenanthridines
      has been developed. This metal-free protocol provides a novel nitrogen
      incorporation transformation using azides as the nitrogen source.
      Phenanthridines, which are of great interest in pharmaceutical and medicinal
      chemistry, are synthesized efficiently in one step. Moreover, the byproducts
      derived from the Schmidt reaction are inhibited, which further demonstrated the
      high chemoselectivity of this transformation. 

PMID- 25875320
TI  - What makes a good home-based nocturnal seizure detector? A value sensitive
      design.
AB  - A device for the in-home detection of nocturnal seizures is currently being
      developed in the Netherlands, to improve care for patients with severe epilepsy.
      It is recognized that the design of medical technology is not value neutral:
      perspectives of users and developers are influential in design, and design
      choices influence these perspectives. However, during development processes,
      these influences are generally ignored and value-related choices remain implicit
      and poorly argued for. In the development process of the seizure detector we
      aimed to take values of all stakeholders into consideration. Therefore, we
      performed a parallel ethics study, using "value sensitive design." Analysis of
      stakeholder communication (in meetings and e-mail messages) identified five
      important values, namely, health, trust, autonomy, accessibility, and
      reliability. Stakeholders were then asked to give feedback on the choice of these
      values and how they should be interpreted. In a next step, the values were
      related to design choices relevant for the device, and then the consequences
      (risks and benefits) of these choices were investigated. Currently the process of
      design and testing of the device is still ongoing. The device will be validated
      in a trial in which the identified consequences of design choices are measured as
      secondary endpoints. Value sensitive design methodology is feasible for the
      development of new medical technology and can help designers substantiate the
      choices in their design. 

PMID- 25875321
TI  - Topochemical polymerization of unsymmetrical aryldiacetylene supramolecules with
      nitrophenyl substituents utilizing C-H???pi interactions.
AB  - Diacetylenes are versatile building blocks, in which many functional groups can
      be incorporated for the construction of new materials with desirable properties.
      In this study, 6-(p or m-nitrophenyl)-3,5-hexadiyne-1-ol (4a or 4b) containing
      nitrophenyl groups (host) and 2-hydroxyethyl groups (guest) in different
      diacetylene terminals were designed to establish an ordered supramolecular
      assembly that is complied with the strict requirements for the topochemical
      polymerization of diacetylenes. Crystal film and bulk crystals of compound 4b
      were obtained successfully by cast film and re-precipitation methods. Both of
      these could photopolymerize to the corresponding regular poly(diacetylene)
      polymer, as evidenced by UV-vis, IR, FL and Raman spectroscopy. The
      electrochemical properties and behaviors of 4a and 4b were also investigated, and
      the results show that the differences between the para and meta positions of the
      mono-phenylacetylene substituents probably result from the topochemical
      polymerization. Thus, m-nitrophenylbutadiyne derivatives with sizeable C-H???pi
      interactions seemed to be effective for the formation of a polymerizable packing,
      which is appropriate for topochemical polymerization.

PMID- 25875322
TI  - Anchoring contextual analysis in health policy and systems research: A narrative
      review of contextual factors influencing health committees in low and middle
      income countries.
AB  - Health committees, councils or boards (HCs) mediate between communities and
      health services in many health systems. Despite their widespread prevalence, HC
      functions vary due to their diversity and complexity, not least because of their
      context specific nature. We undertook a narrative review to better understand the
      contextual features relevant to HCs, drawing from Scopus and the internet. We
      found 390 English language articles from journals and grey literature since 1996
      on health committees, councils and boards. After screening with inclusion and
      exclusion criteria, we focused on 44 articles. Through an iterative process of
      exploring previous attempts at understanding context in health policy and systems
      research (HPSR) and the HC literature, we developed a conceptual framework that
      delineates these contextual factors into four overlapping spheres (community,
      health facilities, health administration, society) with cross-cutting issues
      (awareness, trust, benefits, resources, legal mandates, capacity-building, the
      role of political parties, non-governmental organizations, markets, media, social
      movements and inequalities). While many attempts at describing context in HPSR
      result in empty arenas, generic lists or amorphous detail, we suggest anchoring
      an understanding of context to a conceptual framework specific to the phenomena
      of interest. By doing so, our review distinguishes between contextual elements
      that are relatively well understood and those that are not. In addition, our
      review found that contextual elements are dynamic and porous in nature,
      influencing HCs but also being influenced by them due to the permeability of HCs.
      While reforms focus on tangible HC inputs and outputs (training, guidelines,
      number of meetings held), our review of contextual factors highlights the dynamic
      relationships and broader structural elements that facilitate and/or hinder the
      role of health committees in health systems. Such an understanding of context
      points to its contingent and malleable nature, links it to theorizing in HPSR,
      and clarifies areas for investigation and action. 

PMID- 25875324
TI  - Women's entrepreneurship and intimate partner violence: A cluster randomized
      trial of microenterprise assistance and partner participation in post-conflict
      Uganda (SSM-D-14-01580R1).
AB  - Intimate partner violence is widespread and represents an obstacle to human
      freedom and a significant public health concern. Poverty alleviation programs and
      efforts to economically "empower" women have become popular policy options, but
      theory and empirical evidence are mixed on the relationship between women's
      empowerment and the experience of violence. We study the effects of a successful
      poverty alleviation program on women's empowerment and intimate partner relations
      and violence from 2009 to 2011. In the first experiment, a cluster-randomized
      superiority trial, 15 marginalized people (86% women) were identified in each of
      120 villages (n = 1800) in Gulu and Kitgum districts in Uganda. Half of villages
      were randomly assigned via public lottery to immediate treatment: five days of
      business training, $150, and supervision and advising. We examine intent-to-treat
      estimates of program impact and heterogeneity in treatment effects by initial
      quality of partner relations. 16 months after the initial grants, the program
      doubled business ownership and incomes (p < 0.01); we show that the effect on
      monthly income, however, is moderated by initial quality of intimate partner
      relations. We also find small increases in marital control (p < 0.05), self
      reported autonomy (p < 0.10), and quality of partner relations (p < 0.01), but
      essentially no change in intimate partner violence. In a second experiment, we
      study the impact of a low-cost attempt to include household partners (often
      husbands) in the process. Participants from the 60 waitlist villages (n = 904)
      were randomly assigned to participate in the program as individuals or with a
      household partner. We observe small, non-significant decreases in abuse and
      marital control and large increases in the quality of relationships (p < 0.05),
      but no effects on women's attitudes toward gender norms and a non-significant
      reduction in autonomy. Involving men and changing framing to promote more
      inclusive programming can improve relationships, but may not change gender
      attitudes or increase business success. Increasing women's earnings has no effect
      on intimate partner violence. 

PMID- 25875323
TI  - Negotiating structural vulnerability following regulatory changes to a provincial
      methadone program in Vancouver, Canada: A qualitative study.
AB  - While regulatory frameworks governing methadone maintenance therapy (MMT) require
      highly regimented treatment programs that shape treatment outcomes, little
      research has examined the effects of regulatory changes to these programs on
      those receiving treatment, and located their experiences within the wider context
      of social-structural inequities. In British Columbia (BC), Canada, provincial
      regulations governing MMT have recently been modified, including: replacing the
      existing methadone formulation with Methadose((r)) (pre-mixed and 10 times more
      concentrated); prohibiting pharmacy delivery of methadone; and, prohibiting
      pharmacies incentives for methadone dispensation. We undertook this study to
      examine the impacts of these changes on a structurally vulnerable population
      enrolled in MMT in Vancouver, BC. Qualitative interviews were conducted with 34
      people enrolled in MMT and recruited from two ongoing observational prospective
      cohort studies comprised of drug-using individuals in the six-month period in
      2014 following these regulatory changes. Interview transcripts were analysed
      thematically, and by drawing on the concept of 'structural vulnerability'.
      Findings underscore how these regulatory changes disrupted treatment engagement,
      producing considerable health and social harms. The introduction of
      Methadose((r)) precipitated increased withdrawal symptoms. The discontinuation of
      pharmacy delivery services led to interruptions in MMT and co-dispensed HIV
      medications due to constraints stemming from their structural vulnerability
      (e.g., poverty, homelessness). Meanwhile, the loss of pharmacy incentives limited
      access to material supports utilized by participants to overcome barriers to MMT,
      while diminishing their capacity to assert some degree of agency in negotiating
      dispensation arrangements with pharmacies. Collectively, these changes functioned
      to compromise MMT engagement and increased structural vulnerability to harm,
      including re-initiation of injection drug use and participation in high-risk
      income-generating strategies. Greater attention to the impacts of social
      structural inequities on MMT engagement is needed when modifying MMT programs,
      especially as other jurisdictions are adopting similar changes. Comprehensive
      environmental supports should be provided to minimize adverse outcomes during
      transitional periods. 

PMID- 25875325
TI  - Determinants and Functions of Standardized Assessment Use Among School Mental
      Health Clinicians: A Mixed Methods Evaluation.
AB  - The current study evaluated why and how school mental health clinicians use
      standardized assessment tools in their work with youth and families. Quantitative
      and qualitative (focus group) data were collected prior to and following a
      training and consultation sequence as part of a trial program to assess school
      clinician's (n = 15) experiences administering standardized tools to youth on
      their caseloads (n = 191). Findings indicated that, although assessment use was
      initially somewhat low, clinicians used measures to conduct initial assessments
      with the bulk of their caseloads (average = 62.2%) during the implementation
      period. Clinicians also reported on factors influencing their use of assessments
      at the client, provider, and system levels; perceived functions of assessment;
      student responses to assessment use; and use of additional sources of clinically
      relevant information (primarily educational data) for the purposes of assessment
      and progress monitoring. Implications for the contextual appropriateness of
      standardized assessment and training in assessment tools are discussed.

PMID- 25875326
TI  - Selective inhibitory effects of 50-nm gold nanoparticles on mouse macrophage and
      spleen cells.
AB  - Nanoparticles (NP) are significant to multiple industrial processes, consumer
      products and medical applications today. The health effects of many different
      types of NP, however, are largely unknown. The purpose of this study was to test
      the effects of 50-nm gold NP coated with poly-N-vinylpyrrolidone (PVP) on mouse
      macrophage and spleen cells with and without lipopolysaccharide (LPS), testing
      the hypothesis that the NP would modulate immune responses without being overtly
      toxic. Gold NP had no effect on macrophage viability and, in the absence of LPS,
      they had no effect on tumor necrosis factor (TNF)-alpha production as measured by
      ELISA. The presence of LPS significantly increased the release of TNFalpha from
      the macrophages above no-treatment controls, but increasing gold NP concentration
      led to decreasing release of TNFalpha. The reactive oxygen species (ROS) produced
      by exposed macrophages were also reduced compared to untreated controls, both
      with and without LPS, suggesting some kind of oxygen radical scavenging. In
      splenocyte cultures, gold NP had no effect alone, but significantly reduced the
      release of interleukin (IL)-17 and TNFalpha triggered by LPS. These results
      suggest that the gold NP used here are not cytotoxic to immune cells at these
      concentrations, but may affect cellular responses to infection or inflammation by
      altering the balance of cytokines. 

PMID- 25875327
TI  - Inhalation of the reactive aldehyde acrolein promotes antigen sensitization to
      ovalbumin and enhances neutrophilic inflammation.
AB  - Acrolein (ACR), an alpha,beta-unsaturated aldehyde and a major component of
      tobacco smoke, is a highly reactive electrophilic respiratory irritant implicated
      in asthma pathogenesis and severity. However, few studies have directly
      investigated the influence of ACR exposure on allergen sensitization and
      pulmonary inflammation. The present study was designed to examine the impact of
      ACR inhalation on allergic sensitization to the inhaled antigen ovalbumin (OVA),
      as well as pulmonary inflammation during subsequent OVA challenge. Adult male
      C57BL/6 mice were exposed to inhaled OVA (1%, 30 min/day, 4 days/week) and/or ACR
      (5 ppm, 4 h/day, 4 days/week) over 2 weeks and subsequently challenged with
      aerosolized OVA (1%, 30 min/day) over three consecutive days. Serum anti-OVA IgG1
      levels were increased significantly in animals exposed to both OVA and ACR,
      compared to animals exposed to either OVA or ACR alone. In addition, differential
      cell counts and histological analysis revealed an increase in BAL neutrophils in
      animals exposed to both OVA and ACR. However, exposure to both OVA and ACR did
      not influence mRNA expression of the cytokines il5, il10, il13 or tnfa, but
      significantly increased mRNA expression of ccl20. Moreover, ACR exposure enhanced
      lung mRNA levels of il17f and tgfb1, suggesting development of enhanced
      inhalation tolerance to OVA. Overall, the findings indicate that ACR inhalation
      can promote airway-mediated sensitization to otherwise innocuous inhaled
      antigens, such as OVA, but also enhances immune tolerance, thereby favoring
      neutrophilic airway inflammation. 

PMID- 25875328
TI  - Novel carboxypeptidase A6 (CPA6) mutations identified in patients with juvenile
      myoclonic and generalized epilepsy.
AB  - Carboxypeptidase A6 (CPA6) is a peptidase that removes C-terminal hydrophobic
      amino acids from peptides and proteins. The CPA6 gene is expressed in the brains
      of humans and animals, with high levels of expression during development. It is
      translated with a prodomain (as proCPA6), which is removed before secretion. The
      active form of CPA6 binds tightly to the extracellular matrix (ECM) where it is
      thought to function in the processing of peptides and proteins. Mutations in the
      CPA6 gene have been identified in patients with temporal lobe epilepsy and
      febrile seizures. In the present study, we screened for CPA6 mutations in
      patients with juvenile myoclonic epilepsy and identified two novel missense
      mutations: Arg36His and Asn271Ser. Patients harboring these mutations also
      presented with generalized epilepsy. Neither of the novel mutations was found in
      a control population. Asn271 is highly conserved in CPA6 and other related
      metallocarboxypeptidases. Arg36 is present in the prodomain and is not highly
      conserved. To assess structural consequences of the amino acid substitutions,
      both mutants were modeled within the predicted structure of the enzyme. To
      examine the effects of these mutations on enzyme expression and activity, we
      expressed the mutated enzymes in human embryonic kidney 293T cells. These
      analyses revealed that Asn271Ser abolished enzymatic activity, while Arg36His led
      to a ~50% reduction in CPA6 levels in the ECM. Pulse-chase using radio-labeled
      amino acids was performed to follow secretion. Newly-synthesized CPA6 appeared in
      the ECM with peak levels between 2-8 hours. There was no major difference in time
      course between wild-type and mutant forms, although the amount of radiolabeled
      CPA6 in the ECM was lower for the mutants. Our experiments demonstrate that these
      mutations in CPA6 are deleterious and provide further evidence for the
      involvement of CPA6 mutations in the predisposition for several types of
      epilepsy.